PMID- 16880905
TI  - Photoelectron imaging of propanal by resonant multiphoton ionization via the 3s
      Rydberg state.
AB  - We report the conformationally- and vibrationally-selected photoelectron
      spectroscopy of propanal obtained by resonance-enhanced multiphoton ionization
      (REMPI) using photoelectron imaging. These photoelectron spectra, employing (2 +
      1) ionization via the (n, 3s) Rydberg transitions in the range from 365 to 371
      nm, confirm that there are two stable conformer origins in the lowest ionic
      state, the cis conformer with a co-planar CCCO geometry and a gauche conformer
      with a approximately 119 degrees CCCO dihedral angle. From ab initio calculations
      at the B3LYP/6-311++G** level, we find the gauche conformer is slightly more
      stable, with the energy difference between two conformers determined to be only
      65 cm(-1). In our photoelectron spectra, the vertical ionization potential (IP)
      for the cis conformer of propanal was then determined to be 9.999 (+/-0.003) eV,
      while that of the gauche conformer of propanal was estimated to be 9.944 eV. A
      long vibrational progression in the in-plane CCCO deformation vibrational mode,
      v, for the cis conformer is systematically observed in all photoelectron spectra
      in which this mode is excited, suggesting that the geometry of the ground ionic
      state is significantly different from that of the 3s Rydberg state, particularly
      along the v(15) coordinates.

PMID- 16880906
TI  - Photoelectron imaging following 2 + 1 multiphoton excitation of HBr.
AB  - The photodissociation and photoionization dynamics of HBr via low-n Rydberg and
      ion-pair states was studied by using 2 + 1 REMPI spectroscopy and velocity map
      imaging of photoelectrons. Two-photon excitation at about 9.4-10 eV was used to
      prepare rotationally selected excited states. Following absorption of the third
      photon the unperturbed F (1)Delta(2) and i (3)Delta(2) states ionize directly
      into the ground vibrational state of the molecular ion according to the Franck
      Condon principle and upon preservation of the ion core. In case of the V
      (1)Sigma(+)(0(+)) ion-pair state and the perturbed E (1)Sigma(+)(0(+)), g
      (3)Sigma(-)(0(+)), and H (1)Sigma(+)(0(+)) Rydberg states the absorption of the
      third photon additionally results in a long vibrational progression of HBr(+) in
      the X (2)Pi state as well as formation of electronically excited atomic
      photofragments. The vibrational excitation of the molecular ion is explained by
      autoionization of repulsive superexcited states into the ground state of the
      molecular ion. In contrast to HCl, the perturbed Rydberg states of HBr show
      strong participation of the direct ionization process, with ionic core
      preservation.

PMID- 16880907
TI  - Multiphoton processes of CO at 230 nm.
AB  - High resolution kinetic energy release spectra were obtained for C(+) and O(+)
      from CO multiphoton ionization followed by dissociation of CO(+). The excitation
      was through the CO (B (1)Sigma(+)) state via resonant two-photon excitation
      around 230 nm. A total of 5 and 6 photons are found to contribute to the
      production of carbon and oxygen cations. DC slice and Megapixel ion imaging
      techniques were used to acquire high quality images. Major features in both O(+)
      and C(+) spectra are assigned to the dissociation of some specific vibrational
      levels of CO(+)(X (2)Sigma(+)). The angular distributions of C(+) and O(+) are
      very distinct and those of various features of C(+) are also different. A
      dramatic change of the angular distribution of C(+) from dissociation of CO(+)(X
      (2)Sigma(+), nu(+) = 1) is attributed to an accidental one-photon resonance
      between CO(+)(X (2)Sigma(+), nu(+) = 1) and CO(+)(B (2)Sigma(+), nu(+) = 0) and
      explained well by a theoretical model. Both kinetic energy release and angular
      distributions were used to reveal the underlying dynamics.

PMID- 16880908
TI  - Imaging CIN(3) photodissociation from 234 to 280 nm.
AB  - We report Cl((2)P(3/2)) and Cl*((2)P(1/2)) fragment images following ClN(3)
      photolysis in the 234-280 nm region measured by velocity map imaging. Kinetic
      energy distributions change shape with photolysis wavelength from bimodal at 234
      and 240 nm to single peak at 266 and 280 nm. Where two peaks exist, their ratio
      is significantly different for Cl and Cl* fragments. The single peak of 266 and
      280 nm and the faster peak at 234 and 240 nm are assigned to a Cl + linear-N(3)
      dissociation channel, in agreement with previous work. The slow peak in the
      bimodal distributions is assigned to the formation of a high energy form (HEF) of
      N(3). Candidates for the identity of HEF-N(3) are discussed. Combining our data
      with photofragmentation translational spectroscopy results, we determined the
      threshold for the appearance of HEF-N(3) at 4.83 +/- 0.17 eV photolysis energy.
      This threshold behavior is similar to recently reported results on the wavelength
      dependence of HN(3) photolysis, where the threshold was associated with a ring
      closed isomer of HN(3) on the S(1) potential energy surface. We also note that
      the HEF-N(3) formation threshold observed for ClN(3) occurs where the energy
      available to the products equals the isomerization barrier from linear to cyclic
      N(3).

PMID- 16880909
TI  - Vibrational state-dependent predissociation dynamics of ClO (A (2)Pi(3/2)):
      Insight from correlated fine structure branching ratios.
AB  - We have studied the v'-dependent predissociation dynamics of the ClO A (2)Pi(3/2)
      state using velocity-map ion-imaging. Experimental final correlated state
      branching ratios, i.e. Cl((2)P(J=3/2,1/2)) + O((3)P(J=2,1,0)) channels, have been
      measured for v' = 6-11. We find that the branching ratios are highly variable and
      depend strongly on v', providing a window into the v'-dependent predissociation
      mechanism. A comparison of the experimental results with the recent model of Lane
      et al. (I. C. Lane, W. H. Howie and A. J. Orr-Ewing, Phys. Chem. Chem. Phys.,
      1999, 1, 3087) in both the diabatic and adiabatic limits suggests that the
      dynamics are closer to the diabatic limit. The overall Cl((2)P(J)) branching
      ratios are in good agreement with the diabatic model results. There are
      significant differences, however, between theory and experiment at the correlated
      state level, demonstrating the sensitivity of correlated measurements to the role
      of the exit channel coupling in the predissociation dynamics. The results
      highlight the need for more sophisticated quantum dynamical calculations to
      describe the correlated fine structure branching ratios in this system.

PMID- 16880910
TI  - The role of intermediate state polarization in determination of vector properties
      of the ground state using multiphoton excitation.
AB  - We present a general theory for calculating the vector and geometrical properties
      of the multiphoton excitation of an arbitrary atomic or molecular system. The
      results are applied to study the influence of the polarization of the two-photon
      excited state, which is usually neglected, on the intensity of (2 + 1) resonant
      multiphoton ionization in atoms. Two examples of specific atomic systems of
      practical importance are presented: oxygen and chlorine. For some cases, the
      effect of the polarization of the pre-ionized state can be significant and must
      be properly treated.

PMID- 16880911
TI  - Modification of the velocity distribution of H(2) molecules in a supersonic beam
      by intense pulsed optical gradients.
AB  - We report the acceleration and deceleration of H(2) molecules in a supersonic
      molecular beam by means of its interaction with an intense optical gradient from
      a nanosecond far-off-resonant optical pulse. The strong optical gradients are
      formed in the interference pattern of two intense optical pulses at 532 nm. The
      velocity distribution of the molecular beam, before and after the applied optical
      pulse, is measured by a velocity-mapped ion imaging technique. Changes in
      velocity up to 202 m s(-1)+/- 61 m s(-1) are observed in a molecular beam
      initially travelling at a mean speed of 563 m s(-1). We report the dependence of
      this change in velocity with the strength of the optical gradient applied.

PMID- 16880912
TI  - Velocity map imaging of ion-molecule reactive scattering: the Ar(+)+ N(2) charge
      transfer reaction.
AB  - We present a velocity map imaging spectrometer for the study of crossed-beam
      reactive collisions between ions and neutrals at (sub-)electronvolt collision
      energies. The charge transfer reaction of Ar(+) with N(2) is studied at 0.6, 0.8
      and 2.5 eV relative collision energies. Energy and angular distributions are
      measured for the reaction product N. The differential cross section, as analyzed
      with a Monte Carlo reconstruction algorithm, shows significant large angle
      scattering for lower collision energies in qualitative agreement with previous
      experiments. Significant vibrational excitation of N(+)(2) is also observed. This
      theoretically still unexplained feature indicates the presence of a low energy
      scattering resonance.

PMID- 16880913
TI  - State-correlation matrix of the product pair from F + CD(4)--> DF(nu') + CD(3)(0
      v(2) 0 0).
AB  - The title reaction was investigated under crossed-beam conditions at three
      different collision energies, E(c) = 8.4, 2.76 and 1.46 kcal mol(-1). The
      combination of using a (2 + 1) resonance-enhanced multiphoton ionization for
      tagging state-specific CD(3) products and exploiting a time-sliced velocity
      imaging for ion detection allows us to reveal the coincident information of the
      two product pairs in a state-correlated manner. The pair-correlated results are
      reported for the two product vibrators -- (v(2) = 0, v'), (v(2) = 1, v'), (v(2) =
      2, v') and (v(2) = 3, v')-and the dynamics attributes we examined include product
      state distributions, energy disposals and angular distributions. Together with
      our earlier communications, a rather complete picture of the correlated dynamics
      of the title reaction emerges. One of the major findings, the anti-correlated
      excitations of the two product vibrators at all four energies of this study, can
      qualitatively be understood by kinematics arguments.

PMID- 16880914
TI  - Slice imaging of quantum state-to-state photodissociation dynamics of OCS.
AB  - Slice imaging experiments are reported for the quantum state-to-state
      photodissociation dynamics of OCS. Both one-laser and two-laser experiments are
      presented detecting CO(J) or S((1)D(2)) photofragments from the dissociation of
      hexapole state-selected OCS(v(2) = 0,1,2 / J = 1,2) molecules. We present data
      using our recently developed large frame CCD centroiding detector and have
      implemented a new high speed MCP high voltage pulser with an effective slice
      width of only 6 ns. Slice images are presented for quantum state-to-state
      photolysis, near 230 nm, of vibrationally excited OCS(v(2) = 0,1,2). Two-laser
      pump-probe experiments detecting CO(J = 63 or 64) show a dramatic change in the
      beta parameter for the same final state of CO(J) when the photolysis energy is
      reduced by about 1000 cm(-1). We attribute the observed change from large
      positive to large negative beta to a large increase of the molecular frame
      deflection angle at very slow recoil velocity, due to a breakdown of the axial
      recoil. Two-laser experiments on the S((1)D(2)) fragment reveal single well
      separated rings in the slice images correlating with individual CO(J) states.
      Strong polarization effects of the probe laser are observed, both in the angular
      distribution of the intensity of single S((1)D(2)) rings and in the resolution of
      the radial velocity distribution. It is shown how the broadening of the velocity
      distribution can be reduced by a directed ejection of the electron in the
      ionization process perpendicular to the slice imaging plane. The dissociation
      energy of OCS(v(2) = 0, J = 0) --> CO(J = 0) + S((1)D(2)) is determined with high
      accuracy D(0) = (34 608 +/- 24) cm(-1).

PMID- 16880915
TI  - Photodissociation of thymine.
AB  - We discuss the photochemistry and photodissociation dynamics of thymine as
      revealed by two-colour photofragment Doppler spectroscopy and by one-colour slice
      imaging. Thymine is optically excited into the pipi* state, known to deactivate
      quickly. The H atom photofragment spectra are dominated by two-photon excitation
      processes with subsequent statistical dissociation. This can be explained by
      absorption of a second photon from a long-lived dark state to a highly excited
      state that quickly deactivates to the electronic ground state. No evidence was
      found for an important role of the pisigma* excited state identified in adenine
      and many other heterocyclic molecules.

PMID- 16880916
TI  - Examination of (e,2e) scattering models by comparison of momentum profiles of
      noble gases between experiment and theory.
AB  - Momentum profiles have been measured for the two outermost atomic orbitals of
      noble gases, Ar, Kr and Xe, at incident electron energy of about 2 keV using a
      newly developed multichannel (e,2e) spectrometer. The experimental results
      exhibit significantly improved statistics compared with those achieved in
      previous studies while covering a wide range of momenta up to 3.6 a.u. The
      results are compared with theoretical calculations using four (e,2e) scattering
      models, the plane-wave impulse and Born approximations (PWIA and PWBA), and the
      distorted-wave impulse and Born approximations (DWIA and DWBA). The DWIA and DWBA
      scattering models have been found to satisfactorily reproduce the experimental
      momentum profiles in terms of both shape and intensity over the entire momentum
      range covered, indicating the importance of distorted wave effects for
      quantitatively describing (e,2e) reaction.

PMID- 16880919
TI  - Exploring stem cell biology with small molecules.
AB  - Stem cells hold promise for the treatment of a number of diseases. Small
      molecules serve as useful chemical tools to control stem cell fate and may
      ultimately contribute to development of effective medicines for tissue repair and
      regeneration.

PMID- 16880920
TI  - Optimized protocols for the isolation of specific protein-binding peptides or
      peptoids from combinatorial libraries displayed on beads.
AB  - Many methods have been published by which combinatorial libraries may be screened
      for compounds capable of manipulating the function(s) of a target protein. One of
      the simplest approaches is to identify compounds in a library that bind the
      protein of interest, since these binding events usually occur on functionally
      important surfaces of the protein. These protein-binding compounds could also be
      of utility as protein capture agents in the construction of protein-detecting
      microarrays or related analytical devices and as reagents for the affinity
      purification of proteins from complex mixtures. In this article, we provide
      optimized methods for screening libraries of molecules displayed on the beads on
      which they were synthesized. This is a particularly convenient format for library
      screening for laboratories with limited budgets and modest robotics capabilities.

PMID- 16880922
TI  - Optimizing the affinity and specificity of proteins with molecular display.
AB  - Affinity maturation of receptor-ligand interactions represents an important area
      of academic and pharmaceutical research. Improving affinity and specificity of
      proteins can tailor potency for both in vivo and in vitro applications. A number
      of different display platforms including phage display, bacterial and yeast
      display, ribosome display, and mRNA display can optimize protein affinity and
      specificity. Here, we will review the advantages and disadvantages of these
      molecular display methods with a focus on their suitability for protein affinity
      maturation.

PMID- 16880923
TI  - Protein and small molecule microarrays: powerful tools for high-throughput
      proteomics.
AB  - Advances in genomics and proteomics have opened up new possibilities for the
      rapid functional assignment and global characterization of proteins. Large-scale
      studies have accelerated this effort by using tools and strategies that enable
      highly parallel analysis of huge repertoires of biomolecules. Organized
      assortments of molecules on arrays have furnished a robust platform for rapid
      screening, lead discovery and molecular characterization. The essential advantage
      of microarray technology is attributed to the massive throughput attainable,
      coupled with a highly miniaturized platform--potentially driving discovery both
      as an analytical and diagnostic tool. The scope of microarrays has in recent
      years expanded impressively. Virtually every biological component--from diverse
      small molecules and macromolecules (such as DNA and proteins) to entire living
      cells--has been harnessed on microarrays in attempts to dissect the bewildering
      complexity of life. Herein we highlight strategies that address challenges in
      proteomics using microarrays of immobilized proteins and small molecules. Of
      specific interest are the techniques involved in stably immobilizing proteins and
      chemical libraries on slide surfaces as well as novel strategies developed to
      profile activities of proteins on arrays. As a rapidly maturing technology,
      microarrays pave the way forward in high-throughput proteomic exploration.

PMID- 16880924
TI  - The mechanism of action of ramoplanin and enduracidin.
AB  - The lipoglycodepsipeptide antibiotic ramoplanin is proposed to inhibit bacterial
      cell wall biosynthesis by binding to intermediates along the pathway to mature
      peptidoglycan, which interferes with further enzymatic processing. Two sequential
      enzymatic steps can be blocked by ramoplanin, but there is no definitive
      information about whether one step is inhibited preferentially. Here we use
      inhibition kinetics and binding assays to assess whether ramoplanin and the
      related compound enduracidin have an intrinsic preference for one step over the
      other. Both ramoplanin and enduracidin preferentially inhibit the
      transglycosylation step of peptidoglycan biosynthesis compared with the MurG
      step. The basis for stronger inhibition is a greater affinity for the
      transglycosylase substrate Lipid II over the MurG substrate Lipid I. These
      results provide compelling evidence that ramoplanin's and enduracidin's primary
      cellular target is the transglycosylation step of peptidoglycan biosynthesis.

PMID- 16880926
TI  - Small molecules in an RNAi world.
AB  - In this Opinion, we compare and contrast small molecules and RNAi. We discuss the
      advantages and disadvantages of both technologies focusing on timing,
      specificity, dose and therapeutic use.

PMID- 16880927
TI  - Microfluidics-based systems biology.
AB  - Systems biology seeks to develop a complete understanding of cellular mechanisms
      by studying the functions of intra- and inter-cellular molecular interactions
      that trigger and coordinate cellular events. However, the complexity of
      biological systems causes accurate and precise systems biology experimentation to
      be a difficult task. Most biological experimentation focuses on highly detailed
      investigation of a single signaling mechanism, which lacks the throughput
      necessary to reconstruct the entirety of the biological system, while high
      throughput testing often lacks the fidelity and detail necessary to fully
      comprehend the mechanisms of signal propagation. Systems biology experimentation,
      however, can benefit greatly from the progress in the development of microfluidic
      devices. Microfluidics provides the opportunity to study cells effectively on
      both a single- and multi-cellular level with high-resolution and localized
      application of experimental conditions with biomimetic physiological conditions.
      Additionally, the ability to massively array devices on a chip opens the door for
      high-throughput, high fidelity experimentation to aid in accurate and precise
      unraveling of the intertwined signaling systems that compose the inner workings
      of the cell.

PMID- 16880921
TI  - Inductive tissue engineering with protein and DNA-releasing scaffolds.
AB  - Cellular differentiation, organization, proliferation and apoptosis are
      determined by a combination of an intrinsic genetic program, matrix/substrate
      interactions, and extracellular cues received from the local microenvironment.
      These molecular cues come in the form of soluble (e.g. cytokines) and insoluble
      (e.g. ECM proteins) factors, as well as signals from surrounding cells that can
      promote specific cellular processes leading to tissue formation or regeneration.
      Recent developments in the field of tissue engineering have employed biomaterials
      to present these cues, providing powerful tools to investigate the cellular
      processes involved in tissue development, or to devise therapeutic strategies
      based on cell replacement or tissue regeneration. These inductive scaffolds
      utilize natural and/or synthetic biomaterials fabricated into three-dimensional
      structures. This review summarizes the use of scaffolds in the dual role of
      structural support for cell growth and vehicle for controlled release of tissue
      inductive factors, or DNA encoding for these factors. The confluence of molecular
      and cell biology, materials science and engineering provides the tools to create
      controllable microenvironments that mimic natural developmental processes and
      direct tissue formation for experimental and therapeutic applications.

PMID- 16880928
TI  - A novel peptide microarray for protein detection and analysis utilizing a dry
      peptide array system.
AB  - A novel dry peptide microarray system has been constructed that affords a
      practical solution for protein detection and analysis. This system is an array
      preparation and assay procedure under dry conditions that uses designed peptides
      as non-immobilized capture agents for the detection of proteins. The system has
      several advantages that include its portability and ease-of-use, as well as the
      fact that vaporization of sample solutions need not be considered. In this study,
      various proteins have been characterized with an alpha-helical peptide mini
      library. When proteins were added to the peptide library array, the fluorescent
      peptides showed different fluorescent intensities depending on their sequences.
      The patterns of these responses could be regarded as 'protein fingerprints'
      (PFPs), which are sufficient to establish the identities of the target proteins.
      Furthermore, statistical analysis of the resulting PFPs was performed using
      cluster analysis. The PFPs of the proteins were clustered successfully depending
      on their families and binding properties. Additionally, the target protein was
      characterized using a nanolitre system and could be detected down to 1.2 fmol.
      These studies imply that the dry peptide array system is a promising tool for
      detecting and analyzing target proteins. The dry peptide array will play a role
      in development of high-throughput protein-detecting nano/micro arrays for
      proteomics and ligand screening studies.

PMID- 16880929
TI  - Simple SNP typing assay using a base-discriminating fluorescent probe.
AB  - We have developed a new concept involving a single-step homogeneous method for
      single-nucleotide polymorphism (SNP) typing. In this method, a probe containing
      base-discriminating fluorescent (BDF) bases is added to a sample solution. BDF
      base-containing DNA usually shows only a weak fluorescence, but emits a strong
      blue fluorescence when it recognizes a target base at a specific site in a
      hybridized strand. By utilizing this feature, a simple mix-and-read SNP typing
      assay was achieved without any tedious probe-designing or washing processes for
      exclusion of hybridization error or any addition of DNA-modifying enzymes. This
      is very different from conventional methods. We simultaneously analyzed a number
      of samples with ease, with a high accuracy, using our BDF assay.

PMID- 16880930
TI  - Methodology of reversible protein labeling for ratiometric fluorescent
      measurement.
AB  - The first fluorescent labeling technology, which can induce not only an increase
      in the fluorescence intensity but also a shift in the fluorescence spectrum, has
      been developed for "ratiometric" measurements for a protein by utilizing a newly
      designed "field-sensitive" fluorescent probe and its corresponding unique amino
      acid tag.

PMID- 16880931
TI  - Immunomodulatory effects of Pseudomonas aeruginosa quorum sensing small molecule
      probes on mammalian macrophages.
AB  - Pseudomonas aeruginosa produces the quorum sensing signalling molecule N-(3
      oxododecanoyl)-L-homoserine lactone (OdDHL). This natural product not only
      coordinates production of virulence factors by the bacterium, but also has
      immunomodulatory effects on the host organism. Immunomodulatory small molecules
      are valuable for immunology research and are potential therapeutics for
      autoimmune diseases such as rheumatoid arthritis, and immunosuppressive drugs
      following organ transplants. We describe the total synthesis of OdDHL using solid
      supported reagents and scavengers, which has the potential to be used for
      automated analogue synthesis. OdDHL and four analogues were tested for their
      ability to activate or inhibit release of the pro-inflammatory mediators tumour
      necrosis factor alpha (TNFalpha) and nitric oxide (NO) from equine or murine
      macrophages (immune cells). Two of the analogues showed substantial
      immunomodulatory activity with these macrophages. One analogue showed differing
      species selectivity, being a potent antagonist in mouse cells, but a partial
      agonist in horse-derived macrophages. These compounds have the therapeutic
      potential to be used for protecting animals from bacterial septic shock.

PMID- 16880933
TI  - Establishment of the platform for reverse chemical genetics targeting novel
      protein-protein interactions.
AB  - In the "drug discovery" era, protein-protein interaction modules are becoming the
      most exciting group of targets for study. Although combinatorial libraries and
      active natural products are rapidly and systemically being equipped by both for
      profit and not-for-profit organizations, complete drug-screening systems have not
      been achieved. There is a growing need for the establishment of drug discovery
      assays for highly effective utilization of the collected small molecules on a
      large scale. To generate drug-screening systems, we plan to identify novel
      protein-protein interactions that may participate in human diseases. The
      interactions have been identified by MS/MS analysis following immunoprecipitation
      using antibodies prepared from our cDNA projects. The intracellular pathway
      involving the identified interaction is computationally constructed, which then
      clarifies its relationship to the candidate disease. The development of reverse
      chemical genetics based on such information should help us to realize a
      significant increment in the number of drug discovery assays available for use.
      In this article, I describe our strategy for drug discovery and then introduce
      the applicability of fluorescence intensity distribution analysis (FIDA) and the
      expression-ready constructs called "ORF trap clones" to reverse chemical
      genetics.

PMID- 16880934
TI  - Molecular mechanisms of ethylene signaling in Arabidopsis.
AB  - Ethylene is a gaseous plant hormone involved in several important physiological
      processes throughout a plant's life cycle. Decades of scientific research devoted
      to deciphering how plants are able to sense and respond to this key molecule have
      culminated in the establishment of one of the best characterized signal
      transduction pathways in plants. The ethylene signaling pathway starts with the
      perception of this gaseous hormone by a family of membrane-anchored receptors
      followed by a Raf-like kinase CTR1 that is physically associated with the
      receptors and actively inhibits downstream components of the pathway. A major gap
      is represented by the mysterious plant protein EIN2 that genetically works
      downstream of CTR1 and upstream of the key transcription factor EIN3.
      Transcriptional regulation by EIN3 and EIN3-family members has emerged as a key
      aspect of ethylene responses. The major components of this transcriptional
      cascade have been characterized and the involvement of post-transcriptional
      control by ubiquitination has been determined. Nevertheless, many aspects of this
      pathway still remain unknown. Recent genomic studies aiming to provide a more
      comprehensive view of modulation of gene expression have further emphasized the
      ample role of ethylene in a myriad of cellular processes and particularly in its
      crosstalk with other important plant hormones. This review aims to serve as a
      guide to the main scientific discoveries that have shaped the field of ethylene
      biology in the recent years.

PMID- 16880935
TI  - A multi-analytical platform approach to the metabonomic analysis of plasma from
      normal and Zucker (fa/fa) obese rats.
AB  - Plasma obtained from 20 week old normal Wistar-derived and Zucker (fa/fa) rats
      was analysed using a number of different analytical methodologies to obtain
      global metabolite profiles as part of metabonomic investigations of animal models
      of diabetes. Samples were analysed without sample pre-treatment using 1H NMR
      spectroscopy, after acetonitrile solvent protein precipitation by ultra
      performance liquid chromatography-MS (UPLC-MS) and after acetonitrile protein
      precipitation and derivatisation for capillary gas chromatography-MS (GC-MS).
      Subsequent data analysis using principal components analysis revealed that all
      three analytical platforms readily detected differences between the plasma
      metabolite profiles of the two strains of rat. There was only limited overlap
      between the metabolites detected by the different methodologies and the
      combination of all three methods of metabolite profiling therefore provided a
      much more comprehensive profile than would have been provided by their use
      individually.

PMID- 16880936
TI  - Conformational chemistry of surface-attached calmodulin detected by acoustic
      shear wave propagation.
AB  - A thickness shear-mode acoustic wave device, operated in a flow-through format,
      was used to detect the binding of ions or peptides to surface-attached
      calmodulin. On-line surface attachment of the protein was achieved by
      immobilisation of the biotinylated molecule via a neutravidin-biotin linkage onto
      the surface of the gold electrode of the detector. The interaction between
      calmodulin, and calcium and magnesium ions induced an increase in resonant
      frequency and a decrease in motional resistance, which were reversible on washing
      with buffer. Interestingly, the changes in resonant frequency and motional
      resistance induced by the binding were opposite to the normal operation of the
      detector. The response was interpreted as a decrease in surface coupling (partial
      slip at the liquid/solid interface) instigated by exposure of hydrophobic domains
      on the protein, and an increase in the thickness, and hence effective wavelength,
      of the acoustic device, corresponding to an increase in the length of calmodulin
      by 1.5 A. This result is consistent with the literature value of 4 A. In
      addition, the interaction of the protein with peptide together with calcium ions
      was detected successfully, despite the relatively low molecular mass of the 2-kDa
      peptide. These results confirm the potential of acoustic wave physics for the
      detection of changes in the conformational chemistry of monolayer of biochemical
      macromolecules at the solid/liquid interface.

PMID- 16880937
TI  - The comparative metabonomics of age-related changes in the urinary composition of
      male Wistar-derived and Zucker (fa/fa) obese rats.
AB  - The global metabolite profiles of endogenous compounds excreted in urine by male
      Wistar-derived and Zucker (fa/fa) obese rats were investigated from 4 to 20 weeks
      of age using both 1H NMR spectroscopy and HPLC-TOF/MS with electrospray
      ionisation (ESI). Multivariate data analysis was then performed on the resulting
      data which showed that the composition of the samples changed with age, enabling
      age-related metabolic trajectories to be constructed. At 4 weeks it was possible
      to observe differences between the urinary metabolite profiles from the two
      strains, with the difference becoming more pronounced over time resulting in a
      marked divergence in their metabolic trajectories at 8-10 weeks. The changes in
      metabolite profiles detected using 1H NMR spectroscopy included increased protein
      and glucose combined with reduced taurine concentrations in the urine of the
      Zucker animals compared to the Wistar-derived strain. In the case of HPLC-MS a
      number of ions were found to be present at increased levels in the urine of 20
      week old Zucker rats compared to Wistar-derived rats including m/z 71.0204,
      111.0054, 115.0019, 133.0167 and 149.0454 (negative ion ESI) and m/z 97.0764 and
      162.1147 (positive ion ESI). Conversely, ions m/z 101.026 and 173.085 (negative
      ion ESI) and m/z 187.144 and 215.103 (positive ion ESI) were present in decreased
      amounts in urine from Zucker compared to Wistar-derived rats. Metabolite
      identities proposed for these ions include fumarate, maleate, furoic acid,
      ribose, suberic acid, carnitine and pyrimidine nucleoside. The utility of
      applying metabonomics to understanding disease processes and the biological
      relevance of some of the findings are discussed.

PMID- 16880939
TI  - Chemogenomics: drug discovery's panacea?
AB  - Chemogenomics aims towards the systematic identification of small molecules that
      interact with the products of the genome and modulate their biological function.
      This Opinion article summarizes the different knowledge-based chemogenomics
      strategies that are followed and outlines the challenges and opportunities that
      will impact drug discovery. Chemogenomics aims towards the systematic
      identification of small molecules that interact with the products of the genome
      and modulate their biological function. While historically the approach is based
      on efforts that systematically explore target gene families like kinases, today
      additional knowledge-based systematization principles are followed within early
      drug discovery projects which aim to biologically validate the targets and to
      identify starting points for chemical lead optimization. While the expectations
      of chemogenomics are very high, the reality of drug discovery is quite sobering
      with very high project attrition rates. This article summarizes the different
      knowledge-based chemogenomics strategies that are followed and outlines the
      challenges and potential opportunities that will impact drug discovery.

PMID- 16880940
TI  - Ultra-sensitive and quantitative characterization of proteomes.
AB  - Electrospray ionization mass spectrometry combined with high efficiency capillary
      liquid chromatography provides high sensitivity and broad dynamic range
      measurements for the characterization of biological macromolecules in complex
      matrices, and is an increasingly powerful analytical tool for systems biology
      research.

PMID- 16880941
TI  - Identification of genes involved in the sensitivity to antitumour drug 17
      allylamino,17-demethoxygeldanamycin (17AAG).
AB  - In the present study we analysed the gene expression database provided by the
      National Cancer Institute in an attempt to correlate activity profiles of
      geldanamycin, 17AAG and 11 other analogues in 60 human tumor cell lines with
      their gene expression profiles determined by the cDNA microarray technique. On
      the basis of the activity profiles two classes of geldanamycin analogues could be
      distinguished, having geldanamycin and 17AAG, respectively, as prototype
      compounds (denominated as gelda-like and 17AAG-like classes). Application of the
      "soft" statistical methodology of PLS (partial least squares modelling in latent
      variables or projections to latent structures) allowed us to evaluate the
      influence of each gene expression target in determining the therapeutical
      responses. The transcript encoding the translocating chain-associated membrane
      protein (TRAM) showed a significant statistical correlation with activity
      profiles of 17AAG. In order to validate the role of TRAM in determining
      sensitivity to 17AAG we induced a selective knocking-down of this transcript by
      the RNA interference methodology in H226 non-small cell lung carcinoma cell line.
      The efficiency of double-stranded RNA oligonucleotides (short-interfering RNAs,
      siRNAs) was determined by measuring TRAM mRNA levels by quantitative real-time RT
      PCR at different times (24-72 hours) after siRNA lipotransfection. A significant
      increase in chemosensitivity to 17AAG was observed in siRNA-silenced cells.
      Although a number of factors may affect tumour sensitivity to 17AAG the present
      methodology allowed us to dissect out a single parameter which may be partly
      responsible for its activity.

PMID- 16880942
TI  - Covalent modification of a melanoma-derived antigenic peptide with a natural
      quinone methide. Preliminary chemical, molecular modelling and immunological
      evaluation studies.
AB  - A LigandFit shape-directed docking methodology was used to identify the best
      position at which the melanoma-derived MHC class-I HLA-A2-binding antigenic
      peptide ELAGIGILTV could be modified by attaching a small molecule capable of
      fitting at the interface of complementary determining regional (CDR) loops of a T
      cell receptor (TCR) while triggering T-cell responses. The small molecule
      selected here for determining the feasibility of this alternative track to
      chemical alteration of antigenic peptides was the electrophilic quinone methide
      (+)-puupehenone (), a natural product that belongs to a family of marine
      metabolites capable of expressing immunomodulatory activities. A preliminary
      chemical reactivity model study revealed the efficacy of the thiol group of a
      cysteine (C) side-chain in its nucleophilic addition reaction with in a regio-
      and diastereoselective manner. The best TCR/HLA-A2 ligand [i.e., ELAGCGILTV-S
      puupehenol ()] then identified by the LigandFit docking procedure was synthesized
      and used to pulse HLA-A2(+) T2 cells for T-cell stimulation. Among the ELAGIGILTV
      specific T-cell clones we tested, five of them recognized the conjugate in spite
      of its low binding affinity for the HLA-A2 molecules. The resulting T-cell
      stimulation was determined through the intracytoplasmic secretion of IFN-gamma
      and the percentage of T-cells thus activated. These highly encouraging results
      indicate that small non-peptidic natural product-derived molecules attached onto
      the central part of an antigenic peptide can fit at the TCR/HLA-A2 interface with
      induction of T-cell responses.

PMID- 16880943
TI  - Investigation of differentially expressed proteins due to the inhibitory effects
      of berberine in human liver cancer cell line HepG2.
AB  - The investigation of differentially expressed proteins was used together with
      other techniques to study the inhibitory effects of two different doses of
      berberine in human liver cancer cell line HepG2. For HepG2 cells treated with
      24.0 mg l(-1) of berberine, an increase in the sub G(0) phase that was indicative
      of cell death was observed in cell cycle analysis with flow cytometry. However,
      no significant increase in sub G(0) was observed in HepG2 cells treated with 4.0
      mg l(-1) of berberine. Using flow cytometric analysis, significant activation of
      caspase 3 was not observed with HepG2 cells treated with 4.0 and 24.0 mg l(-1) of
      berberine. In this work, labeling of cells with stable isotope was not used in
      the proposed method developed. The whole cell lysates from the control and
      treated cells were digested with trypsin and the peptides were separated by two
      dimensional (cation exchange and reversed phase) liquid chromatography and tandem
      mass spectrometry. Our preliminary data showed that the proposed platform
      provided a rapid approach to study the molecular mechanism due to the inhibitory
      effects of different doses of the berberine on HepG2 cell lines. This included a
      network of proteins involved in mitogen-activated protein kinase (MAPK)
      phosphorelay systems, metabolism, regulation of cell cycle and DNA damage
      response. The differentially expressed proteins identified using the current
      approach were consistent with the data obtained from cell cycle analysis with
      flow cytometry.

PMID- 16880944
TI  - Screening chemical microarrays: methods and applications.

PMID- 16880946
TI  - The impact of systems biology and biosimulation on drug discovery and
      development.
AB  - Drug discovery and development involves a series of difficult, systematic
      decision-making exercises, each of which is based on data acquired from bioassays
      and clinical trials. Since assays and trials are designed to elucidate the
      underlying pathophysiology of a disease, it is not sufficient to merely acquire
      data, but one must also interpret those findings in the context of the physiology
      they are meant to represent. Recently, these efforts have been enhanced by the
      use of biosimulation as a means of integrating and interpreting the vast new data
      sets generated by classically designed systems biology studies. Only when data
      describing gene expression, cell function, and whole-body physiology are
      interpreted in the context of integrated system function, will current error
      rates experienced during drug discovery and development be minimized.

PMID- 16880947
TI  - Disposable real-time microPCR device: lab-on-a-chip at a low cost.
AB  - We have designed, fabricated and tested a real-time micro polymerase chain
      reaction (microPCR) system. It consists of a microscope glass cover slip placed
      on top of a micromachined silicon chip integrated with a heater and a temperature
      sensor. A single microL of a sample containing DNA was placed on the glass and
      encapsulated with mineral oil to prevent the evaporation of water, thus forming a
      virtual reaction chamber (VRC). The PCR chip required half a second to heat up
      from 72 to 94 degrees C and two seconds to cool from 94 to 55 degrees C,
      corresponding to a cooling rate of -20 K s(-1). The real-time PCR yield was
      determined by a fluorescence method. The melting curve analysis method as well as
      capillary electrophoresis was performed to determine the purity of the PCR
      product. As the glass slip is disposable, cross-contamination from sample to
      sample is eliminated. The total cost of running the PCR is given by the value of
      the cover slip and its treatment.

PMID- 16880948
TI  - Micropatterning polyvinyl alcohol as a biomimetic material through soft
      lithography with cell culture.
AB  - Integrating inorganic materials with specific biological systems requires a
      complex set of properties that can mimic physiological function to create
      microchip devices. Several factors in the material including the spatial location
      of the cellular attachment heavily influence the control of this functionality
      and must be dictated to parallel in vivo characteristics. In this work, we
      demonstrate polyvinyl alcohol (PVA) for use in emulating these properties to
      produce a highly robust and functional biomaterial as a microchip. We show the
      utility of PVA for cellular patterning using soft lithography. Based on these
      results, PVA can be applied in a diversity of areas including tissue engineering,
      biomimetics, and cellular micropatterning.

PMID- 16880949
TI  - An altered oxidant defense system in red blood cells affects their ability to
      release nitric oxide-stimulating ATP.
AB  - A novel microflow technique is used to demonstrate that a weakened oxidant
      defense system found in diabetic erythrocytes leads to decreased levels of
      deformation-induced release of adenosine triphosphate (ATP) from erythrocytes.
      Addition of an oxidant to rabbit erythrocytes resulted in a 63% decrease in
      deformation-induced ATP release before eventually recovering to a value that was
      statistically equivalent to the initial value. Inhibition of glucose-6-phosphate
      dehydrogenase prevents recovery from the oxidant attack. Finally, results
      indicated that the ATP release from the erythrocytes of type II diabetics (91 nM
      +/- 10 nM) was less than half of that measured from the erythrocytes of healthy
      controls (190 +/- 10 nM). These data suggest that the antioxidant status of
      erythrocytes is a critical determinant in the ability of these cells to release
      ATP, a known nitric oxide stimulus.

PMID- 16880950
TI  - A peptidomimetic siRNA transfection reagent for highly effective gene silencing.
AB  - RNA interference (RNAi) techniques hold forth great promise for therapeutic
      silencing of deleterious genes. However, clinical applications of RNAi require
      the development of safe and efficient methods for intracellular delivery of small
      interfering RNA (siRNA) oligonucleotides specific to targeted genes. We describe
      the use of a lipitoid, a cationic oligopeptoid-phospholipid conjugate, for non
      viral transfection of synthetic siRNA oligos in cell culture. This peptidomimetic
      delivery vehicle allows for efficient siRNA transfection in a variety of human
      cell lines with negligible toxicity and promotes extensive downregulation of the
      targeted genes at both the protein and the mRNA level. We compare the lipitoid
      reagent to a standard commercial transfection reagent. The lipitoid is highly
      efficient even in primary IMR-90 human lung fibroblasts in which other commercial
      reagents are typically ineffective.

PMID- 16880954
TI  - Molecular mechanisms of enzyme-catalysed halogenation.
AB  - Since their discovery, halogenated metabolites have been somewhat of a biological
      peculiarity and it is only now that we are beginning to realize the full extent
      of their medicinal value. With the exception of the well characterized
      haloperoxidases, most of the biosynthetic enzymes and mechanisms responsible for
      the halogenations have remained elusive. The crystal structures of two
      functionally diverse halogenases have been recently solved, providing us with new
      and exciting mechanistic detail. This new insight has the potential to be used
      both in the development of biomimetic halogenation catalysts and in engineering
      halogenases, and related enzymes, to halogenate new substrates. Interestingly,
      these new structures also illustrate how the evolution of these enzymes mirrors
      that of the monooxygenases, where the cofactor is selected for its ability to
      generate a powerful oxygenating species. In this highlight article we will
      examine the proposed catalytic mechanisms of the halogenases and how these relate
      to their structures. In addition, we will consider how this chemistry might be
      harnessed and developed to produce novel enzymatic activity.

PMID- 16880955
TI  - Proteomic patterns for cancer diagnosis--promise and challenges.
AB  - Proteomic patterns have been discovered for a variety of cancers and cancer
      related diseases. The platforms used have been both mass spectrometry and
      microarrays and the incorporation of computer informatics has resulted in
      innovative possibilities for novel diagnostics.

PMID- 16880956
TI  - Proteomics technology in systems biology.
AB  - It has now become apparent that a full understanding of a biological process
      (e.g. a disease state) is only possible if all biomolecular interactions are
      taken into account. Systems biology works towards understanding the intricacies
      of cellular life through the collaborative efforts of biologists, chemists,
      mathematicians and computer scientists and recently, a number of laboratories
      around the world have embarked upon such research agendas. The fields of genomics
      and proteomics are foundational in systems biology studies and a great deal of
      research is currently being conducted in each worldwide. Moreover, many
      technological advances (particularly in mass spectrometry) have led to a dramatic
      rise in the number of proteomic studies over the past two decades. This short
      review summarizes a selection of technological innovations in proteomics that
      contribute to systems biology studies.

PMID- 16880957
TI  - Myriaporone 3/4 structure--activity relationship studies define a pharmacophore
      targeting eukaryotic protein synthesis.
AB  - Myriaporones are naturally occurring compounds which structurally resemble the
      southern hemisphere of the tedanolide family of macrolide antitumor agents.
      Despite the fact that myriaporone 3/4 represents only a portion of tedanolide, it
      nonetheless retains much of its biological activity. We show here that like
      tedanolide, myriaporone 3/4 inhibits protein synthesis and proliferation of
      mammalian cells with low nanomolar potencies but displays no prokaryotic growth
      inhibitory effect. Moreover, myriaporone 3/4 displays a very rapid, reversible
      and p21-independent activity to block S phase progression in mammalian cells.
      Structure-activity relationship studies revealed that the C18-C19 epoxide and the
      C14 hydroxymethyl group (tedanolide numbering) of myriaporone 3/4 are required
      for cell cycle inhibition. These constitute previously unidentified and/or novel
      pharmacophores for myriaporone 3/4. Our results show that the important
      biological activities associated with the structurally complex tedanolides are
      present and can be harnessed in the chemically much simpler myriaporones. This
      greatly increases the value of the latter as investigative tools for biochemical
      research as well as for development of potential therapeutics.

PMID- 16880958
TI  - Fluorescence technologies for the investigation of chemical libraries.

PMID- 16880959
TI  - Feedback dynamics and cell function: Why systems biology is called Systems
      Biology.
AB  - A new paradigm, like Systems Biology, should challenge the way research has been
      conducted previously. This Opinion article aims to present Systems Biology, not
      as the application of engineering principles to biology but as a merger of
      systems- and control theory with molecular- and cell biology. In our view, the
      central dogma of Systems Biology is that it is system dynamics that gives rise to
      the functioning and function of cells. The concepts of feedback regulation and
      control of pathways and the coordination of cell function are emphasized as an
      important area of Systems Biology research. The hurdles and risks for this area
      are discussed from the perspective of dynamic pathway modelling. Most of all, the
      aim of this article is to promote mathematical modelling and simulation as a part
      of molecular- and cell biology. Systems Biology is a success if it is widely
      accepted that there is nothing more practical than a good theory.

PMID- 16880960
TI  - Functional gene-discovery systems based on libraries of hammerhead and hairpin
      ribozymes and short hairpin RNAs.
AB  - Abundant information about the nucleotide sequence of the human genome has become
      readily available and it is now necessary to develop methods for the
      identification of genes that are involved in important cellular, developmental
      and disease-related processes. Identification methods based on the activities of
      hammerhead and hairpin ribozymes and of short hairpin RNAs (shRNAs), whose target
      specificities are coupled with loss-of-function phenotypes, have received
      increasing attention as possible tools for the rapid identification of key genes
      involved in such processes. We describe here recent advances that have been made
      with libraries of ribozymes and shRNAs and compare the advantages of the
      different types of library. The use of such libraries has already revealed new
      details of several important physiological phenomena.

PMID- 16880961
TI  - Design of compound libraries based on natural product scaffolds and protein
      structure similarity clustering (PSSC).
AB  - Recent advances in structural biology, bioinformatics and combinatorial chemistry
      have significantly impacted the discovery of small molecules that modulate
      protein functions. Natural products which have evolved to bind to proteins may
      serve as biologically validated starting points for the design of focused
      libraries that might provide protein ligands with enhanced quality and
      probability. The combined application of natural product derived scaffolds with a
      new approach that clusters proteins according to structural similarity of their
      ligand sensing cores provides a new principle for the design and synthesis of
      such libraries. This article discusses recent advances in the synthesis of
      natural product inspired compound collections and the application of protein
      structure similarity clustering for the development of such libraries.

PMID- 16880962
TI  - Electrophoretic and mass spectrometric strategies for profiling bacterial
      lipopolysaccharides.
AB  - Capillary electrophoresis (CE) is a high-resolution separation technique that has
      been widely used for trace analysis in biological samples. On-line capillary
      electrophoresis-electrospray mass spectrometry (CE-MS) was developed for the
      analysis of lipopolysaccharide (LPS) glycoforms from the gram-negative bacteria,
      Haemophilus influenzae. In this paper, we report on the application of CE-MS to
      characterize structural differences in O-deacylated LPS samples from H.
      influenzae strains Rd 11.7 and 375.1. The resolution capability of on-line CE-MS
      was first demonstrated by analysis of a complex LPS mixture from H. influenzae
      strain Rd 11.7. This strain contains a mixture of isomeric glycoforms differing
      in the number and positions of hexose moieties. Sialic acid containing glycoforms
      were also determined. Structural features of LPS from a lic1 mutant of H.
      influenzae strain 375 (375.1) were studied using on-line CE-MS/MS. With the
      separation provided by CE, two isomeric glycoforms differing in the location of
      phosphoethanolamine substituents were characterized by tandem mass spectrometry.

PMID- 16880963
TI  - One-step, non-denaturing isolation of an RNA polymerase enzyme complex using an
      improved multi-use affinity probe resin.
AB  - The rapid isolation of protein complexes is critical to the goal of establishing
      protein interaction networks. High-throughput methods for identifying protein
      binding partners in a way suitable for mass spectrometric identification and
      structural analysis are required and small molecule/peptide interactions provide
      the key. We have now shown that a redesigned resin derivatized with a
      bisarsenical dye can be used to isolate the Shewanella oneidensis RNA polymerase
      core enzyme with a tetracysteine-tagged RNA polymerase A as bait protein. A
      critical advantage of this method is the ability to release the intact complex
      using a mild, one-step procedure with a competing dithiol. In addition to the
      identification of the core complex, additional interaction partners, including
      universal stress protein, were identified. These results provide a path forward
      to identifying how changes in critical protein complexes over time modulate cell
      function.

PMID- 16880964
TI  - Protease profiling using a fluorescent domino peptide cocktail.
AB  - Five hexapeptides were prepared containing, in a domino-type arrangement, all 25
      possible dipeptides between (1) aromatic, (2) hydrophobic, (3) positively
      charged, (4) negatively charged, and (5) small and polar amino acids. The
      peptides were fluorescence labeled at the N-terminus with a (7-coumaryl)oxyacetyl
      group, allowing the selective detection of N-terminal cleavage products. The five
      peptides were used as a cocktail reagent in an HPLC analysis. The cocktail
      produced specific cleavage patterns, or fingerprints, for a variety of proteases.
      This domino peptide cocktail can be used as a general reagent for protease
      identification and functional profiling.

PMID- 16880965
TI  - Synthesis of covalent DNA-protein conjugates by expressed protein ligation.
AB  - Semisynthetic DNA-protein conjugates are versatile tools for many applications in
      bioanalytics and nanobiotechnology. We here report a method based on expressed
      protein ligation (EPL) for the site-specific coupling of cysteine-modified DNA
      oligomers with recombinant intein-fusion proteins. The latter contain a C
      terminal thioester, enabling the mild and highly specific reaction with N
      terminal cysteine compounds. To conveniently couple commercially available DNA
      oligomers with cysteine groups a universal chemical modifier was developed,
      containing a protected cysteine and an amino-reactive N-hydroxysuccinimide group
      connected by a hexaethyleneglycol moiety. Using maltose-binding protein (MBP) and
      green fluorescent protein mutant EYFP as a model systems, we demonstrate the
      feasibility of this approach, as well as the integrity and functionality of the
      DNA-protein conjugates synthesized. We anticipate that our concept will enable
      many applications, such as the generation of large arrays of surface-bound,
      recombinant proteins assembled by means of DNA-directed immobilization.

PMID- 16880966
TI  - Protein immunosensor using single-wall carbon nanotube forests with
      electrochemical detection of enzyme labels.
AB  - Vertically aligned arrays of single-wall carbon nanotubes (SWNT forests) on
      pyrolytic graphite surfaces were developed for amperometric enzyme-linked
      immunoassays. Improved fabrication of these SWNT forests utilizing aged nanotube
      dispersions provided higher nanotube density and conductivity. Biosensor
      performance enhancement was monitored using nanotube-bound peroxidase enzymes
      showing a 3.5-fold better sensitivity for H2O2 than when using fresh nanotubes to
      assemble the forests, and improved detection limits. Absence of improvements by
      electron mediation for detection of H2O2 suggested very efficient electron
      exchange between nanotubes and enzymes attached to their ends. Protein
      immunosensors were made by attaching antibodies to the carboxylated ends of
      nanotube forests. Utilizing casein/detergent blocking to minimize non-specific
      binding, a detection limit of 75 pmol mL(-1) (75 nM) was achieved for human serum
      albumin (HSA) in unmediated sandwich immunosensors using horseradish peroxidase
      (HRP) labels. Mediation of the immunosensors dramatically lowered the detection
      limit to 1 pmol mL(-1) (1 nM), providing significantly better performance than
      alternative methods. In the immunosensor case, the average distance between HRP
      labels and nanotube ends is presumably too large for efficient direct electron
      exchange, but this situation can be overcome by electron mediation.

PMID- 16880967
TI  - NMR studies on Cu(II)-peptide complexes: exchange kinetics and determination of
      structures in solution.
AB  - The interaction of copper(II) with histidine containing peptides has recently
      acquired renewed interest following the established link between abnormal protein
      behaviour in neurodegenerative processes and unpaired copper homeostasis. Five
      peptide sequences taken from the amyloid precursor protein and the prion protein
      were considered. Addition of paramagnetic Cu(II) ions to solutions of such
      peptides was not found to severely affect the appearance of NMR spectra, thus
      limiting the usual approach for structural determination. Exchange kinetics was
      shown to play a major role in determining the observed paramagnetic spin-lattice
      relaxation rates. Two independent methods were suggested for evaluating the
      exchange rates of His-containing peptides from the copper-coordination sphere and
      to calculate copper-proton distances. In such a way NMR was demonstrated to have
      the potential of providing detailed structures of the Cu(II)-peptide complexes in
      solution.

PMID- 16880969
TI  - Crosslinking of diene-modified DNA with bis-maleimides.
AB  - The chemical crosslinking of modified nucleic acids via the Diels-Alder reaction
      is reported. For this purpose, 1,3-butadiene derived building blocks were
      incorporated into complementary oligodeoxynucleotides. Treatment of the obtained
      duplex with difunctional dienophiles results in the clean crosslinking of the two
      strands. Non-crosslinked adducts arising from a single Diels-Alder reaction of a
      maleimide to only one strand were not observed, indicating that the first
      reaction is the rate determining step of the overall process. Based on their
      thermal denaturation profiles, the crosslinked hybrids behave like two separate,
      hairpin-like structures, rather than like a single, continuous duplex.

PMID- 16880968
TI  - Identification of the F1F0 mitochondrial ATPase as a target for modulating skin
      pigmentation by screening a tagged triazine library in zebrafish.
AB  - A triazine-based combinatorial library of small molecules was screened in
      zebrafish to identify compounds that produced interesting phenotypes. One
      compound (of 1536 screened) induced a dramatic increase in the pigmentation of
      early stage zebrafish embryos. This compound, PPA, was also found to increase
      pigmentation in cultured mammalian melanocytes. The cellular target was
      identified as the mitochondrial F1F0-ATP synthase (ATPase) by affinity
      chromatography. Oligomycin, a small molecule known to inhibit the mitochondrial
      ATPase, competed with PPA for its cellular target in melanocytes. In addition,
      PPA was shown to alter the membrane potential of mitochondria, consistent with
      inhibition of the mitochondrial ATPase. Thus, PPA has been successfully used as a
      chemical probe in a forward chemical genetic approach to establish a link between
      the phenotype and the protein. The results attest to the power of screening small
      molecule libraries in zebrafish as a means of identifying mammalian targets and
      suggest the mitochondrial ATPase as a target for modulating pigmentation in both
      melanocytes and melanoma cells.

PMID- 16880972
TI  - "Chromatomics" the analysis of the chromatome.
AB  - Chromatin is a highly complex mixture of proteins and DNA that is involved in the
      regulation and coordination of gene expression within the eukaryotic nucleus.
      Changes in chromatin structure can convey heritable changes of gene activity in
      response to external stimuli without altering the primary DNA sequence. This
      epigenetic inheritance of particular traits very likely plays a major role during
      evolutionary processes. It is however, still ill-defined how this non DNA
      mediated inheritance is accomplished at a molecular level. The advent of new
      methods to systematically study genome-wide changes in chromatin condensation,
      DNA methylation levels, RNA synthesis and the association of specific proteins or
      protein modifications now allows a thorough investigation of changes in chromatin
      structure and function in response to environmental alterations. We would like to
      review some of these global approaches and to introduce the term "chromatomics"
      for the systematic analysis of the DNA, RNA and protein content of the genetic
      material in the eukaryotic nucleus.

PMID- 16880973
TI  - Glycosyltransferases involved in the biosynthesis of biologically active natural
      products that contain oligosaccharides.
AB  - A unique characteristic of carbohydrates is their structural diversity which is
      greater than that of many other classes of biological compounds. Carbohydrate
      containing natural products show many different biological activities and some of
      them have been developed as drugs for medical use. The biosynthesis of
      carbohydrate-containing natural products is catalysed by glycosyltransferases. In
      this review we will present information on the function of glycosyltransferases
      involved in the biosynthesis of oligosaccharide antibiotics focusing especially
      on urdamycins and landomycins, two angucycline antibiotics with interesting
      antitumor activities. We will also discuss the use of glycosyltransferases in
      combinatorial biosynthesis to generate new "hybrid" antibiotics.

PMID- 16880974
TI  - Disulfiram, an old drug with new potential therapeutic uses for human cancers and
      fungal infections.
AB  - Disulfiram, a drug used to treat alcoholism, has recently been indicated to play
      a primary as well as an adjuvant role in the treatment of many cancers and in the
      reversal of fungal drug-resistance. This review discusses the molecular mechanism
      of action of disulfiram and its potential use in the treatment of human cancers
      and fungal infections.

PMID- 16880975
TI  - Identification of base-specific contacts in protein-DNA complexes by
      photocrosslinking and mass spectrometry: a case study using the restriction
      endonuclease SsoII.
AB  - Specific protein-nucleic acid interactions are of paramount importance for the
      propagation, maintenance and expression of genetic information. Restriction
      endonucleases serve as model systems to study the mechanisms of DNA recognition
      by proteins. SsoII is a Type II restriction endonuclease that recognizes the
      double stranded sequence downward arrow CCNGG and cleaves it in the presence of
      Mg(2+)-ions, as indicated. SsoII shows sequence similarity over a stretch of
      approximately 70 amino acid residues with several other restriction endonucleases
      that recognize a similar sequence as SsoII (Cfr10I, EcoRII, NgoMIV, PspGI). In
      NgoMIV this stretch is involved in DNA recognition and cleavage, as shown by the
      crystal structure analysis of an enzyme-product complex. To find out whether the
      presumptive DNA recognition region in SsoII is indeed in contact with DNA we have
      photocrosslinked SsoII with an oligodeoxyribonucleotide in which the first
      guanine of the recognition sequence was replaced by 5-iodouracil. Following
      digestion by trypsin, the peptide-oligodeoxyribonucleotide conjugate was purified
      by Fe(3+)-IMAC and then incubated with hydrogen fluoride, which hydrolyzes the
      oligodeoxyribonucleotide to yield the peptide-deoxyuridine conjugate. The site of
      photocrosslinking was identified by MALDI-TOF-MS and MALDI-TOF-MS/MS to be
      Trp189, adjacent to Arg188, which aligns with Arg194 in NgoMIV, involved in
      recognition of the second guanine in the NgoMIV recognition sequence G downward
      arrow CCGGC. This result confirms previously published conclusions drawn on the
      basis of a mutational analysis of SsoII. The methodology that was employed here
      can be used in principle to identify the DNA binding site of any protein.

PMID- 16880976
TI  - Strict preparation and evaluation of water-soluble hat-stacked carbon nanofibers
      for biomedical application and their high biocompatibility: influence of
      nanofiber-surface functional groups on cytotoxicity.
AB  - Water-soluble H-CNFs modified with a carboxyl group possessed the ability to
      induce TNF-alpha, whereas CHAPS-treated H-CNFs possessed significantly greater
      activity and were also found to activate NF-kappaB reporter activity, to a
      significantly greater level than H-CNFs; furthermore the functional group
      modified or coated on the surface of H-CNFs was a significant cytotoxic factor
      that affected cell activation.

PMID- 16880977
TI  - Construction of biotinylated peptide nanotubes for arranging proteins.
AB  - Three kinds of biotinylated peptides with different linkers between biotin and
      beta-sheet peptide were designed and synthesized. The transmission electron
      microscopy revealed that the biotinylated peptides self-assembled to form a
      tubular structure with external diameter of ca. 60 nm and inner diameter of ca.
      30 nm in an aqueous solution. The anti-biotin antibody effectively bound to
      biotin groups in the peptide nanotubes. The binding of antibody was regulated by
      not only the concentration of the protein in the solution but also the properties
      of biotinylated peptides forming the tubes. The antibody preferentially bound to
      the biotinylated peptide tubes assembled from the peptide with the most
      hydrophilic linker, suggesting that the surface properties and functions of the
      tubular structure were modulated and engineered by the design of the peptides.

PMID- 16880978
TI  - Isolation of a mycoplasma-specific binding peptide from an unbiased phage
      displayed peptide library.
AB  - An important goal in medicine is the development of methods for cell-specific
      targeting of therapeutic molecules to pathogens or pathogen-infected cells.
      However, little progress has been made in cell-specific targeting of bacterially
      infected cells. Using a phage display approach, we have isolated a 20-mer peptide
      that binds to Mycoplasma arginini infected pancreatic beta-cells in tissue
      culture. This peptide binds to M. arginini infected beta-cells 200 times better
      than a control phage and is specific for the infected cells. Furthermore,
      transferring the M. arginini contamination to another cell line renders the newly
      infected cell line susceptible to peptide binding. Immunolocalization experiments
      suggest that the peptide is binding to M. arginini adhered to the cell surface.
      The free synthetic peptide retains its binding in the absence of the phage
      vehicle and tetramerization of the peptide increases its affinity for the
      infected cells. Efforts have been made to use this peptide to eliminate
      Mycoplasma from infected cell lines using ferromagnetic beads coated with the
      selected peptide. A ten-fold reduction of infection was accomplished with one
      fractionation via this approach. Our results suggest that this peptide, isolated
      from an unbiased selection, may be of utility for the detection and reduction of
      Mycoplasma infection in cultured cells. Furthermore, a general implication of our
      findings is that phage display methods may be useful for identifying peptides
      that target a broad array of other biological pathogens in a specific fashion.

PMID- 16880979
TI  - Thermally sensitive micelles self-assembled from poly(N-isopropylacrylamide-co
      N,N-dimethylacrylamide)-b-poly(D,L-lactide-co-glycolide) for controlled delivery
      of paclitaxel.
AB  - Thermally sensitive micelles self-assembled from poly(N-isopropylacrylamide-co-
      N,N-dimethylacrylamide)-b-poly(d,l-lactide-co-glycolide)[P(NIPAAm-co-DMAAm)-b
      PLGA] are fabricated and used as a carrier for the controlled delivery of
      paclitaxel. Paclitaxel is efficiently loaded into the micelles by a membrane
      dialysis method. The lower critical solution temperature (LCST) of the micelles
      is 39.0 degrees C in PBS. Encapsulation efficiency and loading level of
      paclitaxel are affected by the initial loading level of paclitaxel, fabrication
      temperature and polymer composition. The blank and paclitaxel-loaded micelles are
      characterized by particle size analysis (DLS), morphology (TEM and AFM) and
      paclitaxel distribution (NMR, DSC and WAXRD). The micelles are spherical in
      shape, having an average size less than 130 nm. Paclitaxel is molecularly
      distributed within the core of micelles. Sustained release of paclitaxel is
      achieved, which is much faster at a temperature above the LCST than at the normal
      body temperature (37 degrees C). Cytotoxicity of free paclitaxel and paclitaxel
      loaded micelles against a human breast carcinoma cell line (MDA-MB-435S) is
      studied at different temperatures. The cytotoxicity of the paclitaxol-loaded
      micelles is greater as compared to free paclitaxel. Enhanced cytotoxicity is
      achieved by the paclitaxol-loaded micelles when the environmental temperature
      increases slightly above the LCST. Paclitaxel-loaded P(NIPAAm-co-DMAAm)-b-PLGA
      micelles may provide a good formulation for cancer therapy.

PMID- 16880980
TI  - The metabonomics of aging and development in the rat: an investigation into the
      effect of age on the profile of endogenous metabolites in the urine of male rats
      using 1H NMR and HPLC-TOF MS.
AB  - The effect of aging and development in male Wistar-derived rats on the profile of
      endogenous metabolites excreted in the urine was investigated using both (1)H NMR
      spectroscopy and HPLC-TOF MS using electrospray ionisation (ESI). The endogenous
      metabolites were profiled in samples collected from male rats every two weeks
      from just after weaning at 4 weeks up to 20 weeks of age. Multivariate data
      analysis enabled clusters to be visualised within the data according to age, with
      urine collected at 4 and 6 weeks showing the greatest differences by both
      analytical techniques. Markers detected by (1)H NMR spectroscopy included
      creatinine, taurine, hippurate and resonances associated with amino acids/fatty
      acids, which increased with age, whilst citrate and resonances resulting from
      glucose/myoinositol declined. A number of ions were detected by HPLC-MS that were
      only present in urine samples at 4 weeks of age in both positive and negative
      ESI, with a range of ions, including e.g. carnitine, increasing with age. Age
      predictions by PLS-regression modelling demonstrated an age-related trend within
      these data, between 4 and 12 weeks for HPLC-MS and 4-16 weeks for NMR. The
      possible utility of these techniques for metabonomic investigations of age
      related changes in the rat is discussed and the importance of employing suitable
      control animals in pharmacological and toxicological studies is highlighted.

PMID- 16880983
TI  - Cell-cell communication in Gram-negative bacteria.
AB  - Over the last decade or so, a wealth of research has established that bacteria
      communicate with one another using small molecules. These signals enable the
      individuals in a population to coordinate their behaviour. In the case of
      pathogens, this behaviour may include decisions such as when to attack a host
      organism or form a biofilm. Consequently, such signalling systems are excellent
      targets for the development of new antibacterial therapies. In this review, we
      assess how Gram-negative bacteria use small molecules for cell-cell
      communication, and discuss the main approaches that have been developed to
      interfere with it.

PMID- 16880981
TI  - Influence of length on cytotoxicity of multi-walled carbon nanotubes against
      human acute monocytic leukemia cell line THP-1 in vitro and subcutaneous tissue
      of rats in vivo.
AB  - Carbon nanotubes (CNTs) are single- or multi-cylindrical graphene structures that
      possess diameters of a few nanometers, while the length can be up to a few
      micrometers. These could have unusual toxicological properties, in that they
      share intermediate morphological characteristics of both fibers and
      nanoparticles. To date, no detailed study has been carried out to determine the
      effect of length on CNT cytotoxicity. In this paper, we investigated the
      activation of the human acute monocytic leukemia cell line THP-1 in vitro and the
      response in subcutaneous tissue in vivo to CNTs of different lengths. We used 220
      nm and 825 nm-long CNT samples for testing, referred to as "220-CNTs" and "825
      CNTs", respectively. 220-CNTs and 825-CNTs induced human monocytes in vitro,
      although the activity was significantly lower than that of microbial lipopeptide
      and lipopolysaccharide, and no activity appeared following variation in the
      length of CNTs. On the other hand, the degree of inflammatory response in
      subcutaneous tissue in rats around the 220-CNTs was slight in comparison with
      that around the 825-CNTs. These results indicated that the degree of inflammation
      around 825-CNTs was stronger than that around 220-CNTs since macrophages could
      envelop 220-CNTs more readily than 825-CNTs. However, no severe inflammatory
      response such as necrosis, degeneration or neutrophil infiltration in vivo was
      observed around both CNTs examined throughout the experimental period.

PMID- 16880984
TI  - How lipids and proteins interact in a membrane: a molecular approach.
AB  - Membrane proteins in a biological membrane are surrounded by a shell or annulus
      of 'solvent' lipid molecules. These lipid molecules in general interact rather
      non-specifically with the protein molecules, although a few 'hot-spots' may be
      present on the protein where anionic lipids bind with high affinity. Because of
      the low structural specificity of most of the annular sites, the composition of
      the lipid annulus will be rather similar to the bulk lipid composition of the
      membrane. The structures of the solvent lipid molecules are important in
      determining the conformational state of a membrane protein, and hence its
      activity, through charge and hydrogen bonding interactions between the lipid
      headgroups and residues in the protein, and through hydrophobic matching between
      the protein and the surrounding lipid bilayer. Evidence is also accumulating for
      the presence of 'co-factor' lipid molecules binding with high specificity to
      membrane proteins, often between transmembrane alpha-helices, and often being
      essential for activity.

PMID- 16880985
TI  - Polymyxin B: an ode to an old antidote for endotoxic shock.
AB  - Endotoxic shock, a syndrome characterized by deranged hemodynamics, coagulation
      abnormalities, and multiple system organ failure is caused by the release into
      the circulation of lipopolysaccharide (LPS), the structurally diverse component
      of Gram-negative bacterial outer membranes, and is responsible for 60% mortality
      in humans. Polymyxin B (PMB), a cyclic, cationic peptide antibiotic, neutralizes
      endotoxin but induces severe side effects in the process. The potent endotoxin
      neutralizing ability of PMB, however, offers possibilities for designing non
      toxic therapeutic agents for combating endotoxicosis. Amongst the numerous
      approaches for combating endotoxic shock, peptide mediated neutralization of LPS
      seems to be the most attractive one. The precise mode of binding of PMB to LPS
      and the structural features involved therein have been elucidated only recently
      using a variety of biophysical approaches. These suggest that efficient
      neutralization of endotoxin by PMB is not achieved by mere binding to LPS but
      requires its sequestration from the membrane. Incorporation of this feature into
      the design of endotoxin neutralizing peptides should lead to the development of
      effective antidotes for endotoxic shock.

PMID- 16880986
TI  - Xenopus as a model organism in developmental chemical genetic screens.
AB  - Chemical genetics is a potentially powerful tool for studying developmental
      processes in vertebrate systems. We present data showing Xenopus laevis as a
      model organism in which systematic chemical genetic screens can be carried out.
      Previous forward chemical genetic screens, including those with developing
      zebrafish embryos, have demonstrated the nature and value of biological
      information gained with this approach. We show how amenable Xenopus is to
      chemical genetics by investigating a series of compounds either with known
      biochemical effects, or previously identified to give developmental phenotypes,
      on a range of biological functions, including the development of pigmentation,
      the heart and the central nervous system in zebrafish. We have found that the
      compounds give comparable phenotypes when applied to developing Xenopus embryos.
      We have also studied the penetrance and expressivity of these chemical genetic
      phenotypes in relation to genetic variation and the developmental window during
      which the compound is present. Finally, we assess the feasibility and the
      potential throughput of a screen in this vertebrate species.

PMID- 16880987
TI  - ICAT-MS-MS time course analysis of atrophying mouse skeletal muscle cytosolic
      subproteome.
AB  - Skeletal muscle atrophy is a process in which protein degradation exceeds protein
      synthesis, resulting in a decrease of the muscle's physiological cross-sectional
      area and mass, and is often a serious consequence of numerous health problems. We
      used the isotope-coded affinity tag (ICAT) labelling approach and MS-MS to
      protein profile cytosolic subcellular fractions from mouse tibialis anterior
      skeletal muscle undergoing 0, 4, 8, or 16 days of immobilisation-induced atrophy.
      For the validation of peptide and protein identifications statistical algorithms
      were applied to the sequence database search results in order to obtain
      consistent sensitivity/error rates for protein and peptide identifications at
      each immobilisation time point. In this study, we identified and quantified a
      large number of mouse skeletal muscle proteins. At a protein probability (P) of
      P> or = 0.9 (corresponding to a false positive error rate of less than 1%) 807
      proteins were identified (231, 226, 217 for 4, 8, 16 days of immobilisation and
      133 for the control sample, respectively), from which 51 displayed altered
      protein abundance with atrophy. Due to randomness of data acquisition, a full
      time course could be generated only for 62 proteins, most of which displayed
      unchanged protein abundance. In spite of this, useful information about dataset
      characteristics and underlying biological processes could be obtained through
      gene over-representation analysis. 20 gene categories-mainly but not exclusively
      encoded by the subset of overlapping proteins--were consistently found to be
      significantly (p < 0.05) over-represented in all 4 sub-datasets.

PMID- 16880988
TI  - Multifunctional polymeric micelles with folate-mediated cancer cell targeting and
      pH-triggered drug releasing properties for active intracellular drug delivery.
AB  - A new type of multifunctional polymeric micelle drug carrier for active
      intracellular drug delivery was prepared and characterized in this study. The
      micelle is a nano-supramolecular assembly with a spherical core-shell structure,
      and its surface and core were modified with piloting molecules for cancer cells
      and pH-sensitive drug binding linkers for controlled drug release, respectively.
      In order to prepare such micelles, self-assembling amphiphilic block copolymers,
      folate-poly(ethylene glycol)-poly(aspartate hydrazone adriamycin) [Fol-PEG-P(Asp
      Hyd-ADR)], were specially designed and synthesized by installing a molecular
      promoter to enhance intracellular transport, folate (Fol), at the end of the
      shell-forming PEG chain and conjugating the anticancer drug, adriamycin (ADR), to
      the side chain of the core-forming PAsp segment through an acid-sensitive
      hydrazone bond. Because folate-binding proteins (FBP) are selectively
      overexpressed on the cancer cell membranes, the folate-bound micelles (FMA) can
      be guided to the cancer cells in the body, and after the micelles enter the
      cells, hydrazone bonds are cleaved by the intracellular acidic environment (pH 5
      6) so that the drug release profile of the micelles is controlled pH-dependently.
      In this regard, FBP-binding selectivity of the prepared FMA was evaluated by
      surface plasmon resonance (SPR) measurements. The tetrazolium dye method (MTT
      assay) using human pharyngeal cancer cells (KB cell) revealed that FMA
      significantly improved cell growth inhibitory activity in spite of a short
      exposure time due to the selective and strong interaction between folate
      molecules and their receptors. Subsequent flow cytometric analysis showed that
      cellular uptake of FMA significantly increased. Consequently, these findings
      would provide one of the most effective approaches for cancer treatment using
      intracellular environment-targeting supramolecular drug carriers.

PMID- 16880989
TI  - Genotoxicity sensor response correlated with DNA nucleobase damage rates measured
      by LC-MS.
AB  - Responses from "reagentless" DNA-based electrochemical toxicity sensors to DNA
      alkylating agents styrene oxide (SO), diepoxybutane (DEB), and methyl
      methanesulfonate (MMS) were compared to formation rates of total alkylated
      nucleobases in DNA measured by LC-UV-MS. Sensors utilized a catalytic
      metallopolymer in DNA films previously exposed to the damage agents. To achieve
      adequate sensitivity, LC-UV-MS analyses were done on DNA in solution reacted with
      the damage agents, and subsequently hydrolyzed to nucleosides with enzymes.
      Sensor response correlated well with nucleobase-adduct formation rates obtained
      by the molecule-specific analyses. Results confirm that the metallopolymer-DNA
      film sensors can be used to estimate relative DNA damage rates from nucleobase
      adduct-forming chemicals. Results from both methods correlated well with animal
      genotoxicity as estimated by TDL(o) values, the lowest dose producing
      carcinogenicity, in mice and rats. These sensors should be useful for rapid,
      inexpensive screening of moderately and severely genotoxic new chemicals.

PMID- 16880990
TI  - Nucleoside phosphocholine amphiphile for in vitro DNA transfection.
AB  - A new transfection reagent based on nucleoside phosphocholine amphiphile leading
      to high transfection efficacy and low cytotoxicity is described. TEM, ethidium
      bromide displacement assays, agarose gel electrophoresis and SAXS studies support
      the formation of lipoplexes for the transfection of CHO cells.

PMID- 16880993
TI  - Visualising DNA: footprinting and 1-2D gels.
AB  - The study of molecular recognition of DNA by natural and synthetic ligands has
      made enormous progress due in large part to the discovery and development of
      methods for separating DNA fragments by gel electrophoresis in one and two
      dimensions, and for characterizing DNA-ligand complexes by footprinting
      techniques.

PMID- 16880994
TI  - On the track of antitumour ribonucleases.
AB  - Ribonucleases (RNases) are potential alternatives to non-mutagenic antitumour
      drugs. Among these enzymes, onconase, bovine-seminal ribonuclease and the Rana
      catesbeiana and Rana japonica lectins exert a cytotoxic activity that is
      selective for tumour cells. A model for the mechanism of cytotoxicity of these
      RNases which involves different steps is generally accepted. The model predicts
      that cytotoxicity requires interaction of the RNases with the cell membrane and
      internalisation to occur by endocytosis. Then, at a precise point, the RNases are
      translocated to the cytosol where they cleave cellular RNA if they have been able
      to preserve their ribonucleolytic activity. The cleavage of cellular RNA induces
      apoptosis but there is evidence suggesting that RNase-triggered apoptosis does
      not entirely result from the inhibition of protein synthesis. How efficiently a
      particular RNase carries out each of the steps determines its potency as a
      cytotoxin.

PMID- 16880995
TI  - Chiral sensing using a blue fluorescent antibody.
AB  - The chiral sensing of small molecules using a blue fluorescent antibody sensor is
      described.

PMID- 16880996
TI  - Simple reporter gene-based assays for hairpin poly(amide) conjugate permeability
      and DNA-binding activity in living cells.
AB  - Hairpin poly(amide)s (HPs) are sequence specific DNA-binding compounds that have
      engendered considerable interest as potential pharmacological agents to
      manipulate the expression of specific genes. However, recent reports have
      indicated that the ability of HP conjugates to pass through cell membranes is
      sensitive to the cell type employed and the nature of the conjugate. Furthermore,
      while binding of HPs to DNA sequences in vitro is relatively well understood,
      packing of DNA into chromatin in living cells makes predicting the efficiency
      with which a given poly(amide) will bind its cognate site less certain. Previous
      methods to evaluate HP permeability and binding in vivo, while effective, are
      somewhat tedious and qualitative. We report here two related reporter gene-based
      assays that provide a more convenient and quantitative measure of poly(amide)
      permeability and DNA binding activity in living cells. We anticipate that these
      methods will complement existing tools and facilitate the development of HP
      conjugates with the desired biological activity.

PMID- 16880997
TI  - Synthesis of an IGD peptidomimetic with motogenic activity.
AB  - Rational design and synthesis of an IGD peptidomimetic substrate with significant
      motogenic activity.

PMID- 16880998
TI  - Hypoxia-inducible factor prolyl hydroxylase 2 has a high affinity for ferrous
      iron and 2-oxoglutarate.
AB  - Regulation of the hypoxic response in humans is regulated by the post
      translational hydroxylation of hypoxia inducible transcription factor; a
      recombinant form of a human prolyl-4-hydroxylase (PHD2) was characterised and
      shown to have an unexpectedly high affinity for, and to copurify with endogenous
      levels of, its Fe(ii) cofactor and 2-oxoglutarate cosubstrate.

PMID- 16880999
TI  - Interplay between exchange protein directly activated by cAMP (Epac) and
      microtubule cytoskeleton.
AB  - "Exchange protein directly activated by cAMP" (Epac) is a newly discovered cAMP
      receptor that mediates the intracellular cAMP actions in addition to the classic
      cAMP-dependent protein kinase system. In this study, we show that Epac interacts
      directly with tubulin, co-purifies with cellular microtubules, and co-localizes
      with the mitotic spindle assembly. Association with microtubules suppresses Epac
      mediated Rap1 activation, while the binding of Epac promotes microtubule
      formation. These results demonstrate that Epac plays an important role in
      connecting the microtubule cytoskeleton network and intracellular cAMP
      signalling.

PMID- 16881003
TI  - Glucose biosensors as models for the development of advanced protein-based
      biosensors.
AB  - Glucose sensing is used as a model to explore the advantages and problems
      deriving from the use of either enzymes or sugar binding proteins to develop
      stable fluorescence biosensors. We report on a novel approach to address the
      problem of substrate consumption by sensors based on enzymes, namely the
      utilization of apo-enzymes as non-active forms of the protein which are still
      able to bind the substrate/ligand. We also review studies in which derivatization
      of a naturally thermostable sugar-binding protein with a fluorescent probe allows
      quantitative monitoring of glucose binding even after immobilization on a solid
      support.

PMID- 16881004
TI  - Anomalous reflection of gold applicable for a practical protein-detecting chip
      platform.
AB  - A simple, convenient and label-free fiber optic detection system based on the
      characteristic property, 'anomalous reflection (AR)' of gold was developed and
      preliminary experiments showed that the AR signals were sensitive enough to
      monitor protein-peptide interactions on solid surfaces.

PMID- 16881005
TI  - Identification of Gal4 activation domain-binding proteins in the 26S proteasome
      by periodate-triggered cross-linking.
AB  - A common occurrence in biology is that a regulatory peptide, protein, or small
      molecule regulates the activity of a large multi-protein complex through direct
      interactions with a protein(s) in that complex. To characterize the direct
      receptor of the regulatory molecule, one would ideally like to study the native
      system. We report here that periodate-triggered cross-linking of catechol
      containing regulatory factors, followed by two-dimensional electrophoresis and
      Western blotting, is an effective method for the characterization of regulatory
      factor--protein interactions in the context of large multi-protein complexes. We
      demonstrate the utility of this methodology by identifying the Rpt6/Sug1 and
      Rpt4/Sug2 proteins as the direct targets of transcriptional activation domains in
      the 26S proteasome.

PMID- 16881006
TI  - Oxidised guanidinohydantoin (Ghox) and spiroiminodihydantoin (Sp) are major
      products of iron- and copper-mediated 8-oxo-7,8-dihydroguanine and 8-oxo-7,8
      dihydro-2'-deoxyguanosine oxidation.
AB  - 8-Oxo-7,8-dihydroguanine (8-oxoGua), an important biomarker of DNA damage in
      oxidatively generated stress, is highly reactive towards further oxidation. Much
      work has been carried out to investigate the oxidation products of 8-oxoGua by
      one-electron oxidants, singlet oxygen, and peroxynitrite. This report details for
      the first time, the iron- and copper-mediated Fenton oxidation of 8-oxoGua and 8
      oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo). Oxidised guanidinohydantoin
      (Gh(ox)) was detected as the major product of oxidation of 8-oxoGua with iron or
      copper and hydrogen peroxide, both at pH 7 and pH 11. Oxaluric acid was
      identified as a final product of 8-oxoGua oxidation. 8-oxodGuo was subjected to
      oxidation under the same conditions as 8-oxoGua. However, dGh(ox) was not
      generated. Instead, spiroiminodihydantoin (Sp) was detected as the major product
      for both iron and copper mediated oxidation at pH 7. It was proposed that the
      oxidation of 8-oxoGua was initiated by its one-electron oxidation by the metal
      species, which leads to the reactive intermediate 8-oxoGua (+), which readily
      undergoes further oxidation. The product of 8-oxoGua and 8-oxodGuo oxidation was
      determined by the 2'-deoxyribose moiety of the 8-oxodGuo, not whether copper or
      iron was the metal involved in the oxidation.

PMID- 16881007
TI  - Escape from the interferon response associated with RNA interference using
      vectors that encode long modified hairpin-RNA.
AB  - In mammalian cells, siRNAs have been used to induce RNA interference (RNAi) in an
      attempt to prevent nonspecific effects (including the interferon (IFN) response)
      which are caused by long double-stranded RNAs (dsRNAs) of more than 30 bp. In
      this report, we describe a novel and simple strategy for avoiding activation of
      the IFN response by dsRNA. We show that modified hairpin-RNAs (mhRNAs) of more
      than 100 bp, with multiple specific point-mutations within the sense strand and
      transcribed from the U6 or tRNA(Val) promoters, can cause RNAi without inducing
      the IFN pathway genes. Moreover, we demonstrate that the 50-bp mhRNA vector could
      effectively suppress the replication of multiple hepatitis C viruses (the genomes
      of which differ slightly, thus the 21-bp siRNA vector failed to suppress one of
      them). Our findings should enhance the exploitation of RNAi in mammalian cells,
      especially in the field of RNAi therapy against pathogenic viruses.

PMID- 16881008
TI  - Effectiveness of dual and triple antiretroviral therapy in the treatment of HIV
      infected children.
AB  - OBJECTIVE: The use of antiretroviral therapy in HIV-infected children has been a
      widely discussed issue. The aim of this study was to compare the effectiveness of
      dual nucleoside analogue reverse transcriptase inhibitor (NRTI) regimens and
      three-drug regimens [2NRTI+ non-nucleoside reverse transcriptase inhibitor
      (NNRTI) or protease inhibitor (PI)] in a cohort of HIV-infected children.
      METHODS: The study was carried out in a referral center for the management of
      infected children, which is affiliated with the School of Medicine of
      Universidade Federal de Minas Gerais (UFMG). Those children whose antiretroviral
      therapy was implemented between January 1998 and December 2000 and who were
      followed until December 2001 were included in the study. Therapeutic failure or
      death was regarded as the endpoint in our analysis. RESULTS: A total of 101
      patients were assessed, 58 (57.4%) on dual therapy and 43 (42.6%) on triple
      therapy. No statistically significant difference was observed between the groups
      in terms of gender, age, CD4+ count and baseline viral load. The average duration
      of dual therapy was 26.3 months (95%CI 21.3-31.3) and that of triple therapy was
      34.3 months (95%CI 29.2-39.5%). There was therapeutic failure in 33 (56.9%)
      patients on dual therapy and in 11 (25.6%) patients on triple therapy (log rank =
      5.03; p = 0.025). The relative risk of therapeutic failure of the dual therapy
      was 2.2 times higher (95%CI 1.3-3.9). The percentage of initial CD4+ T cells was
      a predictor of risk for therapeutic failure (p = 0.001). Patients on triple
      therapy showed a more remarkable reduction in their viral load (p = 0.001).
      CONCLUSION: Triple therapy was efficient for a longer time period and showed
      better virologic response than dual therapy in this cohort of HIV-infected
      children. Therefore, triple therapy should be the treatment of choice.

PMID- 16881009
TI  - Prevalence of exclusive breastfeeding and its determiners in the first 3 months
      of life in the South of Brazil.
AB  - OBJECTIVE: To determine the prevalence of exclusive breastfeeding during the
      first 3 months of life and its determinant factors in a city in the South region
      of Brazil. METHODS: Prospective study of a cohort of babies born between
      September 2002 and May 2003 in the city of Pelotas, RS. Data were obtained in
      interviews, at maternity units and during home visits, with mothers of babies
      aged between 1 and 3 months. Factors related to the cessation of breastfeeding
      were subjected to univariate, bivariate and multivariate analysis. RESULTS: Nine
      hundred and forty mothers of children aged 3 months or less were interviewed, 39%
      of whom were still exclusively breastfeeding and around 1/3 of whom no longer
      breastfed. Multivariate analysis by logistic regression demonstrated a
      significant association between interruption of exclusive breastfeeding before 3
      months and maternal employment, use of a pacifier, low family income (between one
      and three times the minimum wage), and less than 5 years' paternal education.
      CONCLUSIONS: Exclusive breastfeeding throughout the first 3 months of life is an
      uncommon practice among the population of Pelotas, RS, in particular when the
      mother works away from home, the father has little education and the child is
      given a pacifier, which reinforces the need to continue stimulating exclusive
      breastfeeding during the first months of life.

PMID- 16881010
TI  - ?

PMID- 16881014
TI  - The assessment of plant metabolite profiles by NMR-based methodologies.
AB  - NMR-based metabolic profiling techniques can simultaneously track changes in many
      plant metabolites and have found a number of applications in both systems biology
      and biosafety. Together with multivariate statistical analyses, NMR spectroscopy
      has been successfully applied to the characterisation of various herbs and plant
      products for quality control, authentication, determining geographical origin and
      for detecting adulteration of products. Additionally, the metabolic consequences
      of plant extracts have been demonstrated in experimental animals and in man using
      NMR-based metabonomics approaches to characterise the response. Here the
      application of NMR spectroscopy and chemometric tools for analysing plant-based
      products and their metabolic consequences are considered with particular emphasis
      on deconvolving biological complexity and minimising confounding biological
      variability with analytical 'noise'.

PMID- 16881015
TI  - Inhibitors of acetylcholine esterase in vitro--screening of steroidal alkaloids
      from Fritillaria species.
AB  - 18 alkaloids were successfully isolated from five Fritillaria species and 5
      derivatives were synthesized. Their effects on the bioactivity of human whole
      blood cholinesterase (ChE) were assessed. The results showed that N
      demethylpuqietinone, hupeheninoside, ebeiedinone, yibeinoside A and chuanbeinone
      inhibited the bioactivity of human whole blood ChE at the concentration of 1.0 x
      10 ( - 4) M, with the inhibitory effects of 55.5 +/- 2.7 %, 66.8 +/- 2.0 %, 69.0
      +/- 1.7 %, 71.2 +/- 1.8 % and 70.7 +/- 3.3 %, respectively. The effects of the
      five alkaloids on human red blood cell (RBC) acetylcholinesterase (AChE) and
      human plasma butyrylcholinesterase (BChE) were further studied, and their IC (50)
      values for human RBC AChE were 6.4 +/- 0.003 microM, 16.9 +/- 0.018 microM, 5.7
      +/- 0.004 microM, 6.5 +/- 0.013 microM and 7.7 +/- 0.001 microM, respectively,
      and the IC50 values for human plasma BChE were 12.5 +/- 0.026 microM, 2.1 +/-
      0.005 microM, 5.2 +/- 0.002 microM, 7.3 +/- 0.005 microM and 0.7 +/- 0.001
      microM, respectively. These data suggest, therefore, that N-demethylpuqietinone,
      hupeheninoside, ebeiedinone, yibeinoside A and chuanbeinone have both anti-RBC
      AChE and anti-plasma BChE activities, N-demethylpuqietinone is a selective
      inhibitor of AChE, whereas hupeheninoside and chuanbeinone are the selective
      inhibitors of BChE.

PMID- 16881016
TI  - Neurite outgrowth activity of cyathane diterpenes from Sarcodon cyrneus,
      cyrneines A and B.
AB  - Two new cyathane diterpenes, cyrneines A (1) and B (2), were isolated from the
      mushroom Sarcodon cyrneus. The structures of the novel diterpenoids were
      determined by analysis of their spectroscopic data. Neither cyrneine A nor
      cyrneine B at 100 microM showed cytotoxicity as determined by LDH analysis. The
      stimulating activity on neurite outgrowth of cyrneines was evaluated. Rat
      pheochromocytoma cells (PC12), used as a model system of neuronal
      differentiation, were cultured with cyrneine A (100 microM), cyrneine B (100
      microM) or NGF (100 ng/ml) for 24 h. Interestingly, cyrneines A and B
      significantly promoted neurite outgrowth in addition to NGF as a positive
      control.

PMID- 16881017
TI  - Cytotoxic macrocyclic diterpenoid esters from Euphorbia cornigera.
AB  - Root extract of Euphorbia cornigera Boiss. (Euphorbiaceae) was separated into
      seven (compound 1-7) isolates through multiple Craig's distributions and
      preparative HPLC. The structures and relative configuration of theses compounds
      were established via spectral analyses as 7,8,12- O-triacetyl-3- O-(2
      methylbutanoyl)-ingol (1), 3,8,12- O-triacetyl-7- O-(2-methylbutanoyl = -ingol
      (2), 3,7,12- O-triacetyl-8- O-(2-methylbutanoyl)-ingol (3), 3,7,8- O-triacetyl-12
      O-(2-methylbutanoyl)-ingol (4), 7,12- O-diacetyl-3- O-(2-methylbutanoyl)-8- O
      methylingol (5), 3,12- O-diacetyl-7- O-(2-methylbutanoyl)-8- O-methylingol (6)
      and 3,7- O-diacetyl-12- O-(2-methylbutanoyl)-8- O-methylingol (7). All these
      compounds, except for 2, are novel metabolites and have not been reported
      earlier. It has further been demonstrated that all the compounds (1 - 7) are
      cytotoxic.

PMID- 16881018
TI  - Detection of genetic homogeneity of Panax notoginseng cultivars by sequencing
      nuclear 18S rRNA and plastid matK genes.
AB  - The nuclear 18S rRNA and chloroplast MATK genes of 18 samples of Panax
      notoginseng and its processed material Sanqi (Radix Notoginseng) were analyzed.
      The two genes, regardless of cultivar origin, were found to be identical to
      genotype R1 and M1, respectively, of the published sequences (GenBank accession
      no. D85171 and AB027526). This phenomenon implies that the species is highly
      conserved, which is probably caused by the use of the same strain in cultivation
      and the lack of active mutation in these two genes.

PMID- 16881019
TI  - Activity-guided isolation of scopoletin and isoscopoletin, the inhibitory active
      principles towards CCRF-CEM leukaemia cells and multi-drug resistant CEM/ADR5000
      cells, from Artemisia argyi.
AB  - The ethyl acetate extract of Artemisia argyi leaves showed substantial inhibition
      in a cell proliferation assay using human CCRF-CEM leukaemia cells. Bioassay
      guided fractionation of the extract led to the isolation of scopoletin and
      isoscopoletin as the active principles. Their IC50 values were 2.6 and 4.0
      microM, respectively. Additionally the two substances were tested against the
      multidrug resistant subline, CEM/ADR5000 where they both showed IC50 values of
      1.6 microM. In contrast to the standard cytostatic drugs doxorubicin,
      vincristine, and paclitaxel, CEM/ADR5000 cells therefore did not exhibit cross
      resistance to scopoletin and isoscopoletin.

PMID- 16881020
TI  - A measuring system for the fast simultaneous isotope ratio and elemental analysis
      of carbon, hydrogen, nitrogen and sulfur in food commodities and other biological
      material.
AB  - The isotope ratio of each of the light elements preserves individual information
      on the origin and history of organic natural compounds. Therefore, a multi
      element isotope ratio analysis is the most efficient means for the origin and
      authenticity assignment of food, and also for the solution of various problems in
      ecology, archaeology and criminology. Due to the extraordinary relative
      abundances of the elements hydrogen, carbon, nitrogen and sulfur in some
      biological material and to the need for individual sample preparations for H and
      S, their isotope ratio determination currently requires at least three
      independent procedures and approximately 1 h of work. We present here a system
      for the integrated elemental and isotope ratio analysis of all four elements in
      one sample within 20 min. The system consists of an elemental analyser coupled to
      an isotope ratio mass spectrometer with an inlet system for four reference gases
      (N(2), CO(2), H(2) and SO(2)). The combustion gases are separated by reversible
      adsorption and determined by a thermoconductivity detector; H(2)O is reduced to
      H(2). The analyser is able to combust samples with up to 100 mg of organic
      material, sufficient to analyse samples with even unusual elemental ratios, in
      one run. A comparison of the isotope ratios of samples of water, fruit juices,
      cheese and ethanol from wine, analysed by the four-element analyser and by
      classical methods and systems, respectively, yielded excellent agreements. The
      sensitivity of the device for the isotope ratio measurement of C and N
      corresponds to that of other systems. It is less by a factor of four for H and by
      a factor of two for S, and the error ranges are identical to those of other
      systems.

PMID- 16881021
TI  - Rat lens aldose reductase inhibitory constituents of Nelumbo nucifera stamens.
AB  - Aldose reductase, the principal enzyme of the polyol pathway, has been shown to
      play an important role in the complications associated with diabetes. A methanol
      extract of the stamens of Nelumbo nucifera Gaertn. was shown to exert an
      inhibitory effect on rat lens aldose reductase (RLAR), and thus was fractionated
      using several organic solvents, including dichloromethane, ethyl acetate and n
      butanol. The ethyl acetate-soluble fraction, which manifested potent RLAR
      inhibitory properties, was then purified further via repeated measures of silica
      gel and Sephadex LH-20 column chromatography. Thirteen flavonoids: kaempferol (1)
      and seven of its glycosides (2-9), myricetin 3',5'-dimethylether 3-O-beta-d
      glucopyranoside (10), quercetin 3-O-beta-d-glucopyranoside (11) and two
      isorhamnetin glycosides (12, 13) were isolated from N. nucifera, as well as four
      non-flavonoid compounds: adenine (14), myo-inositol (15), arbutin (16) and beta
      sitosterol glucopyranoside (17). These compounds were all assessed with regard to
      their RLAR-inhibitory properties. Among the isolated flavonoids, those harboring
      3-O-alpha-l-rhamnopyranosyl-(1-->6)-beta-d-glucopyranoside groups in their C
      rings, including kaempferol 3-O-alpha-l-rhamnopyranosyl-(1-->6)-beta-d
      glucopyranoside (5) and isorhamnetin 3-O-alpha-l-rhamnopyranosyl-(1-->6)-beta-d
      glucopyranoside (13), were determined to exhibit the highest degree of rat lens
      aldose reductase inhibitory activity in vitro, evidencing IC(50) values
      (concentration required for a 50% inhibition of enzyme activity) of 5.6 and 9.0
      microm, respectively.

PMID- 16881022
TI  - Selective construction of carbocyclic eight-membered rings by ring-closing
      metathesis of acyclic precursors.
AB  - Although the efficient preparation of cyclooctanoids has remained a long-standing
      objective, a real breakthrough was possible only relatively recently with the
      development of more specific reagents and by the development of new reactions.
      The direct construction of carbocyclic eight-membered rings from acyclic
      precursors is still a challenge, mainly because of unfavorable entropic and
      enthalpic factors that preclude ring formation. This Minireview describes the
      utilization of ring-closing metathesis (RCM) as a new approach to synthesize
      cyclooctanoids.

PMID- 16881024
TI  - Osmium-mediated hexamerization of phenylacetylene.

PMID- 16881023
TI  - Total synthesis of pseudotrienic acid B: a bioactive metabolite from Pseudomonas
      sp. MF 381-IODS.

PMID- 16881025
TI  - Thermodynamic and kinetic enhancement of electrochemical sensitivity by chemical
      coupling in microfluidic systems.

PMID- 16881026
TI  - Thermally responsive vesicles and their structural "locking" through
      polyelectrolyte complex formation.

PMID- 16881027
TI  - An estrogen-platinum terpyridine conjugate: DNA and protein binding and cellular
      delivery.
AB  - A platinum metal complex in which terpyridine joins estradiol (via an ethynyl
      link) to a platinum with a labile ligand (chloride) has been designed,
      synthesised and its X-ray crystal structure determined. The aim of this work was
      to link a targeting motif (in this case estrogen) to a metal-based biomolecule
      recognition unit (the platinum moiety). The target molecule: 17alpha-[4'-ethynyl
      2,2':6',2'-terpyridine]-17beta-estradiol platinum(II) chloride (PtEEtpy) has been
      shown to bind to both human and bovine serum albumin (SA) and to DNA. FTICR mass
      spectrometry shows that the bimolecular units are in each case linked through
      coordination to the platinum with displacement of the chloride ligand. Circular
      dichroism indicates that a termolecular entity involving PtEEtpy, SA and DNA is
      formed. A range of electrospray mass spectrometry experiments showed that the
      PtEEtpy complex breaks and forms coordination bonds relatively easily. A whole
      cell estrogen receptor assay in an estrogen receptor positive cell (MCF-7)
      confirms binding of both EEtpy and PtEEtpy to the estrogen receptor in cells. The
      work demonstrates the concept of linking a targeting moiety (in this case
      estrogen) to a DNA binding agent.

PMID- 16881028
TI  - Gas-phase enantioselectivity of chiral amido[4]resorcinarene receptors.
AB  - Diastereomeric proton-bound [1(L)HA]+ complexes between selected amino acids
      (A=phenylglycine (Phg), tryptophan (Trp), tyrosine methyl ester (TyrOMe),
      threonine (Thr), and allothreonine (AThr)) and a chiral amido[4]resorcinarene
      receptor (1(L)) display a significant enantioselectivity when undergoing loss of
      the amino acid guest A by way of the enantiomers of 2-aminobutanes (B) in the gas
      phase. The enantioselectivity of the B-to-A displacement is ascribed to a
      combination of thermodynamic and kinetic factors related to the structure and the
      stability of the diastereomeric [1(L)HA]+ complexes and of the reaction
      transition states. The results of the present and previous studies allow
      classification of the [1(L)HA]+ complexes in three main categories wherein: i)
      guest A does not present any additional functionalities besides the amino acid
      one (alanine (Ala), Phg, and phenylalanine (Phe)); ii) guest A presents an
      additional alcohol function (serine (Ser), Thr, and AThr); and iii) guest A
      contains several additional functionalities on its aromatic ring (tyrosine (Tyr),
      TyrOMe, Trp, and 3,4-dihydroxyphenylalanine (DOPA)). Each category exhibits a
      specific enantioselectivity depending upon the predominant [1(L)HA]+ structures
      and the orientation of the 2-aminobutane reactant in the relevant adducts
      observed. The results may contribute to the understanding of the exceptional
      selectivity and catalytic properties of enzyme mimics towards unsolvated
      biomolecules.

PMID- 16881029
TI  - Solid-phase synthesis of tetrahydro-beta-carbolines and tetrahydroisoquinolines
      by stereoselective intramolecular N-carbamyliminium Pictet-Spengler reactions.
AB  - A solid-phase method for the synthesis of tri-, tetra-, and pentacyclic compounds
      containing tetrahydro-beta-carboline, tetrahydroisoquinoline or analogous
      scaffolds is presented. The reaction proceeds with high stereoselectivity through
      an intermediate N-carbamyliminium ion that exclusively converts into Pictet
      Spengler-type products with a variety of C-nucleophiles. Amino aldehydes masked
      with 3-Boc-(1,3)-oxazinane (Box) have been synthesized from amino acids, amino
      alcohols, or 2-nitro benzaldehydes. The amino moiety of these masked aldehydes
      has been converted into pentafluorophenyl carbamate to serve as a urea precursor.
      The building blocks were incorporated at the N-terminal of a resin-supported
      dipeptide through urea formation. Subsequent treatment with acid liberated the
      aldehyde quantitatively. A penultimate tryptophan residue gave rise, under the
      acetic conditions, to a spontaneous intramolecular Pictet-Spengler reaction with
      the liberated aldehyde. The reaction proceeded with a high degree of
      stereoselectivity affording tetrahydro-beta-carbolines with a de
      (de=diastereomeric excess) above 95 % and purity in the range of 90-99 %. This
      reaction has been extended to a range of other aromatic C-nucleophiles, including
      substituted indoles, benzenes, pyrene, furan, thiophenes, and benzothiophene with
      comparable stereoselectivity and purity. Prolonged exposure of the benzaldehyde
      derived Pictet-Spengler products to strong acid and air lead to quantitative auto
      oxidation which yielded compounds with a 3,4-dihydro-beta-carboline, a 3,4
      dihydroisoquinoline, or a similar core structure.

PMID- 16881030
TI  - Probing the Lewis acidity and catalytic activity of the metal-organic framework
      [Cu3(btc)2] (BTC=benzene-1,3,5-tricarboxylate).
AB  - An optimized procedure was designed for the preparation of the microporous metal
      organic framework (MOF) [Cu3(btc)2] (BTC=benzene-1,3,5-tricarboxylate). The
      crystalline material was characterized by X-ray diffraction, optical microscopy,
      SEM, X-ray photoelectron spectroscopy, N2 sorption, thermogravimetry, and IR
      spectroscopy of adsorbed CO. CO adsorbs on a small number of Cu2O impurities, and
      particularly on the free CuII coordination sites in the framework. [Cu3(btc)2] is
      a highly selective Lewis acid catalyst for the isomerization of terpene
      derivatives, such as the rearrangement of alpha-pinene oxide to campholenic
      aldehyde and the cyclization of citronellal to isopulegol. By using the ethylene
      ketal of 2-bromopropiophenone as a test substrate, it was demonstrated that the
      active sites in [Cu3(btc)2] are hard Lewis acids. Catalyst stability, re
      usability, and heterogeneity are critically assessed.

PMID- 16881033
TI  - Shaping the future with chemistry: what's in store for chemistry graduates in
      research and industry?

PMID- 16881031
TI  - Total syntheses of the tylophora alkaloids cryptopleurine, (-)-antofine, (-)
      tylophorine, and (-)-ficuseptine C.
AB  - A concise, efficient and modular approach to the tylophora alkaloids is
      described, a family of potent cytotoxic agents that are equally effective against
      drug sensitive and multidrug resistant cancer cell lines. The advantages of the
      chosen route are illustrated by the total syntheses of the
      phenanthroquinolizidine cryptopleurine (1) and the phenanthroindolizidines (-)
      antofine (2), (-)-tylophorine (3), and their only recently isolated congener (-)
      ficuseptine C (4). The key steps consist in a Suzuki cross-coupling between a
      (commercial) boronic acid and a simple aryl-1,2-dihalide followed by elaboration
      of the resulting products into the corresponding 2-alkynyl-biphenyl derivatives
      27, 33, 41 and 46. The latter undergo PtCl2-catalyzed cycloisomerizations with
      formation of the functionalized phenanthrenes 28, 34, 42 and 47, which were
      transformed into the targeted alkaloids by a deprotection/Pictet-Spengler
      annulation tandem. Due to the flexibility and robust character of this approach,
      it might enable a systematic exploration of the pharmacological profile of this
      promising class of bioactive natural products.

PMID- 16881034
TI  - The heat is on ..

PMID- 16881035
TI  - Antibacterial natural products in medicinal chemistry--exodus or revival?
AB  - To create a drug, nature's blueprints often have to be improved through
      semisynthesis or total synthesis (chemical postevolution). Selected contributions
      from industrial and academic groups highlight the arduous but rewarding path from
      natural products to drugs. Principle modification types for natural products are
      discussed herein, such as decoration, substitution, and degradation. The
      biological, chemical, and socioeconomic environments of antibacterial research
      are dealt with in context. Natural products, many from soil organisms, have
      provided the majority of lead structures for marketed anti-infectives.
      Surprisingly, numerous "old" classes of antibacterial natural products have never
      been intensively explored by medicinal chemists. Nevertheless, research on
      antibacterial natural products is flagging. Apparently, the "old fashioned"
      natural products no longer fit into modern drug discovery. The handling of
      natural products is cumbersome, requiring nonstandardized workflows and extended
      timelines. Revisiting natural products with modern chemistry and target-finding
      tools from biology (reversed genomics) is one option for their revival.

PMID- 16881036
TI  - Ultrafast electron crystallography of phospholipids.

PMID- 16881038
TI  - Synthesis and in vitro-anticancer and antimicrobial evaluation of some novel
      quinoxalines derived from 3-phenylquinoxaline-2(1H)-thione.
AB  - Two novel series derived from 3-phenylquinoxaline-2(1H)-thione 2 and 2
      (hydrazinocarbonylmethylthio)-3-phenylquinoxaline 6 have been synthesized. Eight
      out of twenty six new compounds were selected at the National Cancer Institute
      for evaluation of their in vitro-anticancer activity. Among them, compounds 3b,
      3c, 4b, and 4c displayed moderate to strong growth inhibition activity against
      most of the tested sub-panel tumor cell lines with GI(50) 10(-5) to 10(-6 )molar
      concentrations. Compound 4b exhibited a significant value of percent tumor growth
      inhibition against breast cancer at concentration < 10(-8) M. Compound 4c showed
      moderate selectivity towards leukemia cell lines with GI(50) of 1.8 to 3.8 microM
      (selectivity ratio = 5.7). Preliminary antimicrobial testing revealed that
      compounds 7a, 7b, 8a, 11a, and 11b were as active as ampicillin against B.
      subtilis (MIC = 12.5 microg/mL). Compounds 7b and 8a were also nearly as active
      as ampicillin against E. coli (MIC = 12.5 microg/mL). In addition, compounds 4a,
      7b, 10b, and 11a were as active as ampicillin against P. aerugenosa (MIC = 50
      microg/mL). However, compounds 7b, 8a, and 10b showed mild activity against C.
      albicans (MIC = 50 microg/mL). The values of minimum bactericidal concentrations
      indicated that compounds 4a and 7b were bactericidal against B. subtilis and P.
      aerugenosa, respectively, while compound 10b was bactericidal against both
      organisms. However, compound 11a was bactericidal against E. coli, P. aerugenosa,
      and S. aureus.

PMID- 16881039
TI  - Synthesis of new thiazolylthiazolidinylbenzothiazoles and
      thiazolylazetidinylbenzothiazoles as potential insecticidal, antifungal, and
      antibacterial agents.
AB  - A series of 2-{[2'-(3''-chloro-2''-oxo-4''-substitutedaryl-1''-azetidinyl)-1',3'
      thiazol-4'-yl] thio}benzothiazoles (4a-4e) and 2-{[(2'-(2''-substitutedaryl-4''
      thiazolidinon-3''-yl)-1',3'-thiazol-4'-yl]thio}benzothiazoles (5a-5e) have been
      synthesized from 2-[(2'-substitutedarylidenylimino-1',3'-thiazol-4'
      yl)thio]benzothiazoles (3a-3e). The structure of these compounds has been
      elucidated by elemental (C, H, N) and spectral (IR, (1)H-NMR, Mass) analysis.
      Furthermore, compounds 3a-3e, 4a-4e, and 5a-5e were screened for insecticidal
      activity against Periplaneta americana and antifungal, antibacterial activities
      in vitro against different strains of fungi and bacteria. Out of the fifteen
      compounds tested, compound 5b, 2-{[2'-(2''-p-hydroxy-m-methoxyphenyl)-4''
      thiazolidinon-3''-yl)-1',3'-thiazol-4'-yl]thio}benzothiazole, was found to
      possess most prominent insecticidal activity.

PMID- 16881040
TI  - Water, solute, and segmental dynamics in polysaccharide hydrogels.
AB  - Polysaccharide hydrogels have found several applications in the food industry, in
      biomedicine, and cosmetics. The study of polysaccharide hydrogels offers a
      challenging scenario of intrinsic heterogeneities in the crosslinking density and
      large time and space ranges that characterize a number of dynamic processes
      entailing segmental motions, water diffusion, and small-molecule diffusion. The
      understanding of such complex features is essential because of the extensive use
      of polysaccharidic moieties in the food industry, biomedical devices, and
      cosmetics. The study of phenomena occurring at the nanoscale to the mesoscale
      requires the combination of investigative tools to probe different time and
      distance scales and the structural characterization of the networks by
      established methodologies such as swelling and elastic modulus measurements.
      Elastic and quasielastic neutron scattering, and fluorescence recovery after
      photobleaching are emerging methodologies in this field. In this feature article
      we focus, somewhat arbitrarily, on these new approaches because other techniques,
      such as low-resolution proton NMR relaxometry and rheology, have been already
      described thoroughly in the literature. Case examples of polysaccharide hydrogels
      studied by neutron scattering and fluorescence recovery are presented here as
      contributions to the comprehension of the dynamic behavior of physical and
      chemical hydrogels based on polysaccharides. Quasielastic incoherent neutron
      scattering experiment on a Sephadex hydrogel sample at different temperatures.

PMID- 16881041
TI  - Investigating the interactions of hyaluronan derivatives with biomolecules. The
      use of diffusional NMR techniques.
AB  - [Chemical structure: see text] The interactions between a biomaterial and
      biomolecules present in body fluids often determine the fate of the biomaterial.
      This paper presents a study on hyaluronan (HA)-containing materials (in soluble
      or colloidal form) that focuses on their interactions with lipids and proteins
      and for the first time uses PFG NMR as an analytical technique for probing these
      events. The interactions of HA-based polymers with phospholipids (DPPC and DPPG
      liposomes) are shown to depend both on charge and hydrophobicity factors. Despite
      the difference in behavior between albumin (substantially non-adhesive) and
      fibrinogen (adhesive), the interactions of the polymers with proteins do not seem
      to be based on hydrophobic effects but on surface polar interactions.

PMID- 16881042
TI  - Alginate hydrogels as biomaterials.
AB  - [Image: see text] Alginate hydrogels are proving to have a wide applicability as
      biomaterials. They have been used as scaffolds for tissue engineering, as
      delivery vehicles for drugs, and as model extracellular matrices for basic
      biological studies. These applications require tight control of a number of
      material properties including mechanical stiffness, swelling, degradation, cell
      attachment, and binding or release of bioactive molecules. Control over these
      properties can be achieved by chemical or physical modifications of the
      polysaccharide itself or the gels formed from alginate. The utility of these
      modified alginate gels as biomaterials has been demonstrated in a number of in
      vitro and in vivo studies.Micro-CT images of bone-like constructs that result
      from transplantation of osteoblasts on gels that degrade over a time frame of
      several months leading to improved bone formation.

PMID- 16881043
TI  - Development of a model bladder extracellular matrix combining disulfide cross
      linked hyaluronan with decellularized bladder tissue.
AB  - [Image: see text] In this work we investigate the feasibility of modifying
      porcine-derived BAM to include HA with a view to developing a model, artificial
      extracellular matrix for the study of bladder cell-matrix interactions. HA-DPTH
      was incorporated into BAM disks and then cross-linked oxidatively to a disulfide
      containing hydrogel. Disks were seeded with bladder smooth muscle cells (BSMC)
      and UEC under three culture configurations and incubated for 3, 7, and 14 d. At
      each time point, matrix contraction was measured, and media supernatants assayed
      for cell-secreted gelatinase activity. To evaluate cell adherence and
      organization, triple immunofluorescent labeling of cell nuclei, actin
      cytoskeleton, and focal contacts was performed. HA-modified BAM exhibited a
      significant increase in matrix contraction and induced a higher level of cell
      secreted gelatinase activity compared to unmodified BAM. Immunofluorescent
      labeling demonstrated that BSMCs remained adherent to both scaffold types over
      time. The distribution and organization of the cytoskeleton and focal contacts
      did not appear to be altered by the presence of HA. Interestingly, cellular
      infiltration into modified BAM was evident by 7 d and continued beyond 14 d,
      while BSMCs seeded onto unmodified BAM remained localized to the surface out to
      14 d, with minimal infiltration evident only at day 28. These differences in cell
      infiltration support the gelatinase activity results. Increases in cell migration
      and matrix proteolysis in the presence of HA may be contributing factors toward
      BAM remodeling leading to increased matrix contraction with time. The model ECM
      developed in this work will be utilized for future studies aimed at elucidating
      the mechanisms controlling key remodeling events associated with bladder repair.
      Matrix contraction of cell-seeded BAM scaffolds.

PMID- 16881044
TI  - Immobilized hyperbranched glycoacrylate films as bioactive supports.
AB  - [Image: see text] We report on the low-pressure plasma immobilization,
      characterization and application of thin films of hyperbranched glycoacrylates,
      poly(3-O-acryloyl-alpha,beta-D-glucopyranoside) (AGlc), on PTFE-like fluorocarbon
      surfaces. This method is an efficient and versatile way to immobilize sugar
      carrying branched acrylates as thin films of approximately 5 nm thickness on
      polymeric substrates while the functional groups and properties of the
      immobilized molecules are largely retained. The extent of poly(AGlc) degradation
      during plasma immobilization was investigated using FTIR-ATR spectroscopy and
      XPS. The thickness and topography of the immobilized films were characterized
      using spectroscopic ellipsometry and SFM, respectively. Studies of protein
      adsorption, as well as cell adhesion and proliferation on the poly(AGlc)
      surfaces, showed that these materials are suitable for the control of
      biointerfacial phenomena. Fluorescence images of fibronectin adsorbed on to the
      branched glycoacrylate with a mask.

PMID- 16881045
TI  - Approaching the proteoglycome: molecular interactions of proteoglycans and their
      functional output.
AB  - [Image: see text] Through their diverse core protein modules and
      glycan/glycosaminoglycan moieties, proteoglycans may engage in numerous cellular
      and molecular interactions which are dispensable during embryogenesis, are
      essential for the maintenance of a healthy state and are prone to modulation in
      pathological conditions. Proteoglycan interactions may involve binding to other
      structural components of the ECM, to cell surface receptors, to membrane
      associated components, and to soluble signaling molecules, which through this
      interaction may become entrapped in the ECM or sequestered at the cell surface.
      Understanding of these multiple interplays is therefore of paramount importance
      and requires a detailed mapping through what we define as the proteoglycome.

PMID- 16881046
TI  - Engineered bio-active polysaccharides from heparin.
AB  - [Image: see text] Heparin, the well-known anticoagulant polysaccharide, is also
      active in many other biological systems owing to its structural similarity to HS,
      but usually lacks selectivity because it is more highly sulfated. A series of
      straightforward chemical reactions (de-O-sulfation, de-N-sulfation and re-N
      acetylation), carried out to partial or complete extent, were combined, resulting
      in a number of modified heparin polysaccharide derivatives with altered
      properties. These exhibited a range of abilities to promote cell signalling
      through the FGF/FGFR tyrosine kinase signalling system, in an in vitro cell assay
      with combinations of FGF-1, -2, -3 and FGFR 1 and 3. One polysaccharide (N
      acetylated, 6-O- and 2-O-sulfated heparin), with only a fraction (<10(-3)) of the
      anticoagulant activity of heparin (200 U . mg(-1)), promoted FGF-2-mediated
      angiogenesis (10-fold) and therefore had an improved ratio of pro-angiogenic
      activity to anticoagulant activity in excess of 10(4) compared to heparin. These
      results demonstrate that heparin-derived polysaccharides can be engineered for
      selected activities and have potential in a wide range of medical,
      biotechnological and tissue-engineering applications. Effect of selected
      engineered heparin polysaccharides on angiogenesis.

PMID- 16881047
TI  - Expression analysis and evolutionary conservation of the mouse germ cell-specific
      D6Mm5e gene.
AB  - During our search for genes required for gonadal development and function in the
      mouse, we identified D6Mm5e (DNA segment, Chr 6. Miriam Meisler 5, expressed), a
      gene with an expression pattern highly restricted to the embryonic ovary and the
      postnatal testis. Based on RT-PCR, Northern blot, and in situ hybridization
      analyses, we show that D6Mm5e is expressed in the germ cells of the female embryo
      upon their initial entry into meiosis, and in male germ cells during the last
      stages of spermatogenesis. Two transcripts are detected in the gonads resulting
      from the alternative splicing of exon 8. This splicing event does not introduce a
      frame shift, and creates an mRNA product that uses the same stop codon as the
      longer transcript. Although D6Mm5e does not belong to any known protein family
      and does not contain any known protein signature motifs, the high level of
      evolutionary conservation and the cellular and temporal expression suggest that
      D6Mm5e may have a role in male and female gametogenesis. Here we report the gonad
      restricted mRNA expression profile of D6Mm5e in the mouse, and the evolutionary
      conservation of its amino acid sequence.

PMID- 16881048
TI  - Notch synergizes with axin to regulate the activity of armadillo in Drosophila.
AB  - Cell fate decisions require the integration of various signalling inputs at the
      level of transcription and signal transduction. Wnt and Notch signalling are two
      important signalling systems that operate in concert in a variety of systems in
      vertebrates and invertebrates. There is evidence that the Notch receptor can
      modulate Wnt signalling and that its target is the activity and levels of
      Armadillo/beta-catenin. Here, we characterize this function of Notch in relation
      to Axin, a key element in the regulation of Wnt signalling that acts as a
      scaffold for the Shaggy/GSK3beta-dependent phosphorylation of Armadillo/beta
      catenin. While Notch can regulate ectopic Wingless signalling caused by loss of
      function of Shaggy, it can only partially regulate the ectopic Wnt signalling
      induced by the loss of Axin function. The same interactions are observed in
      tissue culture cells where we observe a synergy in between Axin and Notch in the
      regulation of Armadillo/beta-catenin. Our results provide evidence for a function
      of Axin in the regulation of Armadillo that is different from its role as a
      scaffold for GSK3beta.

PMID- 16881049
TI  - High affinity of anti-GM1 antibodies is associated with disease onset in
      experimental neuropathy.
AB  - High antibody affinity has been proposed as a disease determinant factor in
      neuropathies associated with anti-GM1 antibodies. An experimental model of
      Guillain-Barre syndrome, induced by immunization of rabbits with bovine brain
      gangliosides or GM1, was described recently (Yuki et al. [2001] Ann. Neurol.
      49:712-720). We searched plasma from these rabbits, taken at disease onset and 1
      or 2 weeks prior to onset, for the presence of high-affinity anti-GM1 IgG
      antibodies. Affinity was estimated by soluble antigen binding inhibition. High
      affinity antibodies (binding inhibition by 10(-9) M GM1) were detected at disease
      onset but not before. No such difference was found for other antibody parameters
      such as titer, fine specificity, and population distribution. These findings
      support the proposed role of high affinity as an important factor in disease
      induction by anti-GM1 antibodies.

PMID- 16881050
TI  - NADPH oxidase inhibitor diphenyliodonium abolishes lipopolysaccharide-induced
      down-regulation of transferrin receptor expression in N2a and BV-2 cells.
AB  - The activation of cellular inflammatory response is tightly linked to induced
      production of reactive oxygen species (ROS) and nitric oxide (NO), which in turn
      have been identified as important regulators of cellular iron metabolism. In the
      present study, we have used the microglia cell line BV-2 and the neuroblastoma
      cell line N2a to study the regulatory effects of the microbial agent
      lipopolysaccharide (LPS) on the expression of the transferrin receptor (TfR) and
      ferritin in cell lines with different characteristics. The receptor mainly
      responsible for LPS recognition is the Toll-like receptor 4 (TLR4) that triggers
      a variety of intracellular signalling cascades leading to the induction of
      transcription of target genes involved in the innate immune response. Among the
      pathways to be activated is the MAPK cascade leading to the activation of nuclear
      factor-kappaB that induces transcription of a variety of genes, e.g., inducible
      nitric oxide synthase (iNOS). The TLR4-mediated LPS response also induces the
      production of ROS through a mechanism(s) suggested to involve the activation of
      NADPH oxidase(s). This study shows that exposure of BV-2 and N2a cells to LPS
      results in decreased TfR protein levels and increased H-ferritin mRNA levels. The
      LPS down-regulatory effect on TfR protein expression is abolished by the NADPH
      oxidase inhibitor diphenyliodonium (DPI) but is not affected by the free radical
      scavenger N-acetyl-L-cysteine (NAC) or the iNOS inhibitor aminoguanidine (AG).
      The increased H-ferritin mRNA levels in response to LPS are not affected by DPI,
      NAC, or AG.

PMID- 16881051
TI  - Structure and enzymatic properties of a chimeric bacteriophage RB69 DNA
      polymerase and single-stranded DNA binding protein with increased processivity.
AB  - In vivo, replicative DNA polymerases are made more processive by their
      interactions with accessory proteins at the replication fork. Single-stranded DNA
      binding protein (SSB) is an essential protein that binds tightly and
      cooperatively to single-stranded DNA during replication to remove adventitious
      secondary structures and protect the exposed DNA from endogenous nucleases. Using
      information from high resolution structures and biochemical data, we have
      engineered a functional chimeric enzyme of the bacteriophage RB69 DNA polymerase
      and SSB with substantially increased processivity. Fusion of RB69 DNA polymerase
      with its cognate SSB via a short six amino acid linker increases affinity for
      primer-template DNA by sixfold and subsequently increases processivity by
      sevenfold while maintaining fidelity. The crystal structure of this fusion
      protein was solved by a combination of multiwavelength anomalous diffraction and
      molecular replacement to 3.2 A resolution and shows that RB69 SSB is positioned
      proximal to the N-terminal domain of RB69 DNA polymerase near the template strand
      channel. The structural and biochemical data suggest that SSB interactions with
      DNA polymerase are transient and flexible, consistent with models of a dynamic
      replisome during elongation.

PMID- 16881052
TI  - Gene expression and protein localization of calmodulin-dependent
      phosphodiesterase in adult rat retina.
AB  - Calcium calmodulin-dependent cyclic nucleotide phosphodiesterase (PDE1) was
      identified in crude extract and immunolabeled sections of rat retina. Both cAMP
      and cGMP PDE activities were stimulated by calcium-calmodulin (4.7-fold and 2.3
      fold, respectively). To characterize PDE1 isoforms in retinal cells further, we
      used antibodies that specifically recognize PDE1 gene products. PDE1B antibody
      stained a band at molecular mass of 63 kDa whereas PDE1C antibody recognized two
      bands at 74- and 70-kDa molecular masses. Two PDE1A antibodies (against N
      terminal and C-terminal peptides) detected a band at 79 kDa never described
      before. Immunohistochemical analysis showed a distribution of PDE1A in the outer
      retina with a bright fluorescence in the outer segments of photoreceptors. PDE1B
      is uniformly distributed across the retina. PDE1C is confined mainly to the inner
      retina, with a precise localization in the inner nuclear layer. Immunostaining
      with choline acetyltransferase antibody indicates localization in cholinergic
      amacrine cell. The present data provide evidence of expression of PDE1 isoforms
      in mammalian retina with a complementary distribution of PDE1A and PDE1C,
      suggesting different roles in retinal function.

PMID- 16881053
TI  - Emerging developmental model systems.
AB  - This primer briefly describes four emerging animal model systems that promise to
      provide insights into specific aspects of developmental biology. Highlighted here
      are two relatively well-characterized model systems, Gasterosteus aculeatus
      (three-spine stickleback fish) and Schmidtea mediterranea (planarian), as well as
      two organisms on which research is in its infancy, Carollia perspicillata (short
      tailed fruit bat), and the basal metazoan, Trichoplax adhaerens. Scientists who
      helped develop these species into model systems discuss why they chose to
      research these animals.

PMID- 16881054
TI  - IL-1beta, an immediate early protein secreted by activated microglia, induces
      iNOS/NO in C6 astrocytoma cells through p38 MAPK and NF-kappaB pathways.
AB  - In the present study we sought to examine cell-cell interactions by investigating
      the effects of factors released by stimulated microglia on inducible nitric oxide
      (NO) synthase (iNOS) induction in astrocytoma cells. After examining the temporal
      profiles of proinflammatory molecules induced by lipopolysaccharide (LPS)
      stimulation in BV2 microglial cells, iNOS and IL-1beta were observed to be the
      first immediate-response molecules. Removal of LPS after 3 hr stimulation
      abrogated NO release, whereas a full induction of IL-1beta was retained in BV2
      cells. We observed consistently that conditioned medium (CM) from activated
      microglia resulted in the induction of iNOS in C6 cells, and IL-1beta was shown
      to be a key regulator of iNOS induction. An IL-1beta-neutralizing antibody
      diminished NO induction. Incubation with recombinant IL-1beta stimulated NO
      release to a lesser extent compared to microglial CM; co-treatment of LPS and IL
      1beta had a potent, synergistic effect on NO release from C6 cells. Transient
      transfection with MEK kinase 1 (MEKK1) or nuclear factor-kappa B (NF-kappaB)
      expression plasmids induced iNOS, and IL-1beta further enhanced the MEKK1
      response. Furthermore, IL-1beta-mediated NO release from C6 cells was
      significantly suppressed by inhibition of p38 mitogen activated protein kinase
      (MAPK) or NF-kappaB by specific chemical inhibitors. Both IL-1beta and MEKK1
      stimulated p38 and JNK MAPKs, as well as the NF-kappaB pathway, to induce iNOS in
      C6 cells. Microglia may represent an anti-tumor response in the central nervous
      system, which is potentiated by the local secretion of immunomodulatory factors
      that in turn affects astrocytoma (glioma) cells. A better understanding of
      microglia-glioma or microglia-astrocyte interactions will help in the design of
      novel immune-based therapies for brain tumors or neuronal diseases.

PMID- 16881055
TI  - Ocular phenotype in a mouse gene knockout model for infantile neuronal ceroid
      lipofuscinosis.
AB  - Mutations in the human protein palmitoyl thioesterase-1 (PPT-1) gene result in an
      autosomal recessive neurodegenerative disorder designated neuronal ceroid
      lipofuscinosis (NCL), type CLN1, or infantile NCL. Among the symptoms of the CLN1
      disease are accumulation of autofluorescent lysosomal storage bodies in neurons
      and other cell types, seizures, motor and cognitive decline, blindness, and
      premature death. Development of an effective therapy for this disorder will be
      greatly assisted by the availability of suitable animal models. A mouse PPT-1
      gene knockout model has recently been generated. Studies were performed to
      determine whether the mouse model exhibits ocular features of the human CLN1
      disorder. A progressive accumulation of autofluorescent storage material in all
      layers of the retina was observed in the PPT-1 knockout mice. Accompanying the
      storage body accumulation was a modest loss of cells with nuclei in the outer and
      inner nuclear layers. As indicated by electroretinogram (ERG) responses, retinal
      function was only mildly impaired at 4 months of age but was severely impaired by
      8 months, despite only modest changes in retinal morphology. The pupillary light
      reflex (PLR), on the other hand, was exaggerated in the knockout mice. The
      apparent anomaly between the ERG and the PLR findings suggests that disease
      related PLR changes may be due to changes in extraocular signal processing. The
      pronounced ocular phenotype in the PPT-1 knockout mice makes these animals a good
      model for testing therapeutic interventions for treatment of the human CLN1
      disorder.

PMID- 16881056
TI  - Cloning of vertebrate Protogenin (Prtg) and comparative expression analysis
      during axis elongation.
AB  - A murine cDNA encoding Protogenin, which belongs to the DCC/Neogenin family, was
      cloned in a screen performed to identify novel cDNAs regionally expressed in the
      neural plate. Isolation of the putative zebrafish orthologues allowed a
      comparative analysis of the expression patterns of Protogenin genes during
      embryogenesis in different vertebrate species. From mid-gastrulation to early
      somite stages, Protogenin expression is restricted to posterior neural plate and
      mesoderm, with an anterior limit at the level of the rhombencephalon in mouse,
      chicken, and zebrafish. During somitogenesis, the expression profiles in the
      three species share features in the neural tube but present also species-specific
      characteristics. The initiation of Protogenin expression just before
      somitogenesis and its maintenance in the neural tube and paraxial mesoderm during
      this process suggest a conserved role in axis elongation.

PMID- 16881057
TI  - Balancing the bipotential gonad between alternative organ fates: a new
      perspective on an old problem.
AB  - The embryonic gonads give rise to one of two morphologically and functionally
      different organs, a testis or an ovary. Sex determination is the embryonic
      process that determines the developmental fate of the gonad. In mammals, sex
      determination is regulated by a DNA binding protein encoded on the Y chromosome,
      Sry, and it's downstream mediator, Sox9, which trigger testis determination in
      the bipotential gonad. However, evidence suggests that the extracellular signals.
      Fgf9 and Wnt4, are also required to establish divergent organogenesis of the
      gonad. In this review, we discuss how these extracellular signals interface with
      cell-autonomous factors to determine the fate of the mammalian gonad, and we
      derive a model that could provide a molecular explanation for testis
      determination in vertebrates where Sry is absent.

PMID- 16881058
TI  - Apoptosis in the developing mouse heart.
AB  - Apoptosis occurs at high frequency in the myocardium of the developing avian
      cardiac outflow tract (OFT). Up- or down-regulating apoptosis results in defects
      resembling human conotruncal heart anomalies. This finding suggested that
      regulated levels of apoptosis are critical for normal morphogenesis of the four
      chambered heart. Recent evidence supports an important role for hypoxia of the
      OFT myocardium in regulating cell death and vasculogenesis. The purpose of this
      study was to determine whether apoptosis in the outflow tract myocardium occurs
      in the mouse heart during developmental stages comparable to the avian heart and
      to determine whether differential hypoxia is also present at this site in the
      murine heart. Apoptosis was detected using a fluorescent vital dye, Lysotracker
      Red (LTR), in the OFT myocardium of the mouse starting at embryonic day (E) 12.5,
      peaking at E13.5-14.5, and declining thereafter to low or background levels by
      E18.5. In addition, high levels of apoptosis were detected in other cardiac
      regions, including the apices of the ventricles and along the interventricular
      sulcus. Apoptosis in the myocardium was detected by double-labeling with LTR and
      cardiomyocyte markers. Terminal deoxynucleotidyl transferase-mediated
      deoxyuridinetriphosphate nick end-labeling (TUNEL) and immunostaining for cleaved
      Caspase-3 were used to confirm the LTR results. At the peak of OFT apoptosis in
      the mouse, the OFT myocardium was relatively hypoxic, as indicated by specific
      and intense EF5 staining and HIF1alpha nuclear localization, and was surrounded
      by the developing vasculature as in the chicken embryo. These findings suggest
      that cardiomyocyte apoptosis is an evolutionarily conserved mechanism for normal
      morphogenesis of the outflow tract myocardium in avian and mammalian species.

PMID- 16881059
TI  - Design and validation of a synthetic VH repertoire with tailored diversity for
      protein recognition.
AB  - Previous studies have indicated differences in the specificity-determining
      residues (SDRs) of antibodies that recognize haptens, peptides, or proteins.
      Here, we designed a V(H) repertoire based on the human scaffold 3-23/J(H)4 and
      diversification of high and medium-usage SDRs of anti-protein and anti-peptide
      antibodies. The repertoire was synthesized by overlapping polymerase chain
      reaction (PCR) and combined with the V(L) chain of the anti-hen egg-white
      lysozyme (HEL) antibody D1.3. The resulting chimeric single-chain Fv fragments
      (scFvs) phage-displayed library was panned in HEL-coated immunotubes. After two
      rounds of selection under non-stringent conditions, that is, trypsinization after
      2 h of incubation at room temperature, 63 of 167 clones analyzed (38%) were found
      to express scFvs specific to HEL. Twenty clones were characterized by DNA
      sequencing resulting in 10 unique scFvs. Interestingly, the panel of unique scFvs
      was highly diverse, with V(H) sequences differing in 16 of the 17 positions
      variegated in the repertoire. Thus, diverse chemico-physical and structural
      solutions were selected from the library, even when the V(H) repertoire was
      constrained by the V(L) chain of D1.3 to yield binders against a definite region
      of HEL surface. The more often selected scFvs, namely H6-1 and B7-1, which
      differed in eight SDRs, showed levels of expression in E. coli TG1 strain, 6 and
      10 times higher than the parental D1.3 Fv fragment, respectively. Dissociation
      constants (K(Ds)) measured in the BIAcore were 11 and 6.6 nM for H6-1 and B7-1,
      respectively. These values compared well to the K(D) of 4.7 nM measured for D1.3,
      indicating that the V(H) repertoire here designed is a valuable source of
      diverse, well-expressed and high affinity V(H) domains.

PMID- 16881060
TI  - Three Dact gene family members are expressed during embryonic development and in
      the adult brains of mice.
AB  - Members of the Dact protein family initially were identified through binding to
      Dishevelled (Dvl), a cytoplasmic protein central to Wnt signaling. During mouse
      development, Dact1 is detected in the presomitic mesoderm and somites during
      segmentation, in the limb bud mesenchyme and other mesoderm-derived tissues, and
      in the central nervous system (CNS). Dact2 expression is most prominent during
      organogenesis of the thymus, kidneys, and salivary glands, with much lower levels
      in the somites and in the developing CNS. Dact3, not previously described in any
      organism, is expressed in the ventral region of maturing somites, limb bud and
      branchial arch mesenchyme, and in the embryonic CNS; of the three paralogs, it is
      the most highly expressed in the adult cerebral cortex. These data are consistent
      with studies in other vertebrates showing that Dact paralogs have distinct
      signaling and developmental roles and suggest they may differentially contribute
      to postnatal brain physiology.

PMID- 16881061
TI  - Notexin causes greater myotoxic damage and slower functional repair in mouse
      skeletal muscles than bupivacaine.
AB  - Although the myotoxins bupivacaine and notexin are employed for studying
      processes that regulate muscle regeneration after injury, no studies have
      compared their efficacy in causing muscle damage or assessing functional
      regeneration in mouse skeletal muscles. Bupivacaine causes extensive injury in
      rat muscles but its effects on mouse muscles are variable. We compared functional
      and morphological properties of regenerating mouse extensor digitorum longus
      (EDL) muscles after notexin or bupivacaine injection and tested the hypothesis
      that muscle damage would be more extensive and functional repair less complete
      after notexin injection. Bupivacaine caused degeneration of 45% of fibers and
      reduced maximum force (Po) to 42% of control after 3 days. In contrast, notexin
      caused complete fiber breakdown and loss of functional capacity after 3 days (P <
      0.05). At 7 and 10 days after bupivacaine, Po was restored to 65% and 71% of
      control, respectively, whereas Po of notexin-injected muscles was only 10% and
      39% of control at these time-points, respectively (P < 0.05). At 7 and 10 days
      after bupivacaine, approximately 30% of fibers were centrally nucleated
      (regenerating), whereas notexin-injected muscles were comprised entirely of
      regenerating fibers (P < 0.05). The results demonstrate that notexin causes a
      more extensive and complete injury than bupivacaine, and is a useful model for
      studying muscle regeneration in mice.

PMID- 16881062
TI  - Elevated skeletal muscle phosphodiesters in adults using statin medications.
AB  - Elevated skeletal muscle phosphodiesters (PDE) have previously been reported with
      muscle-related disorders. Myalgia is a side effect of using statin cholesterol
      lowering medications and, therefore, statin use may be associated with increased
      skeletal muscle PDE. The effect of cholesterol-lowering drugs on skeletal muscle
      phosphorus metabolites was determined with (31)P magnetic resonance spectroscopy.
      Resting (31)P metabolites of the anterior compartment muscles were measured in
      two groups (n = 20; age, 49 +/- 2 years); half were taking statins and the other
      half were not on these agents. Muscle PDE was 57% greater in the statin group
      than the control group. These data suggest that statin use increases muscle PDE.
      Our findings are particularly relevant due to the increasing use and higher
      dosing of statin medications. Further prospective studies should be performed to
      document a causal relationship between elevated PDE and statin use, in addition
      to quantifying correlates to muscle function.

PMID- 16881063
TI  - Birth and death of cells in limb development: a mapping study.
AB  - Cell death and cell proliferation are basic cellular processes that need to be
      precisely controlled during embryonic development. The developing vertebrate limb
      illustrates particularly well how correct morphogenesis depends on the
      appropriate spatial and temporal balance between cell death and cell
      proliferation. Precise knowledge of the patterns of cell proliferation and cell
      death during limb development is required to understand how their modifications
      may contribute to the generation of the great diversity of limb phenotypes that
      result from spontaneous mutations or induced genetic manipulations. We have
      performed a comprehensive analysis of the patterns of cell death, assayed by
      terminal deoxynucleotidyl transferase-mediated deoxyuridinetriphosphate nick end
      labeling (TUNEL), and cell proliferation, assayed by anti-phosphorylated histone
      H3 immunohistochemistry, in consecutive sections of forelimbs and hindlimbs
      covering an extensive period of chick and mouse limb development. Our results
      confirm and expand previous reports and show common and specific areas of cell
      death for each species. Mitotic cells were found scattered in a uniform
      distribution across the early limb bud, with the exception of the areas of cell
      death in which mitotic cells were scarce. At later stages, mitotic cells were
      seen more abundantly in the digital tips. The aim of the present study was to
      satisfy the need for organized data sets describing these processes, which will
      allow the side-by-side comparison between the two major model organisms of limb
      development, i.e., the mouse and the chick.

PMID- 16881064
TI  - Effects of exercise and creatine on myosin heavy chain isoform composition in
      patients with Charcot-Marie-Tooth disease.
AB  - It is not known whether myosin heavy chain (MHC) content changes in response to
      exercise training or creatine supplementation in subjects with Charcot-Marie
      Tooth disease (CMT). Based on previous data, we hypothesized that resistance
      exercise and creatine would increase the percentage of type I MHC composition in
      the vastus lateralis muscle and that myosin isoform changes would correlate with
      improved chair rise-time in CMT subjects. To test this hypothesis, 18 CMT
      subjects were randomly assigned to either a placebo or creatine group. All
      subjects performed a 12-week, home-based, moderate-intensity resistance training
      program. Chair rise-time was measured before and after the training program.
      Muscle biopsies were obtained from the vastus lateralis before and after the 12
      week program. Gel electrophoresis showed a significant decrease (approximately
      30%) in MHC type I in CMT subjects given creatine supplementation when compared
      with placebo. There was a nonsignificant increase in both MHC type IIa
      (approximately 23%) and MHC type IIx (approximately 7%) in CMT subjects given
      creatine. Reduced MHC type I content and increased MHC type IIa content
      correlated with faster chair rise-times (i.e., improved muscle performance). The
      training-induced change in MHC IIa content was inversely correlated with chair
      rise-time in CMT subjects given creatine. When the two subject groups were
      combined, there was a linear, negative relationship between the change in MHC
      type IIa content and chair rise-time after training and a positive relationship
      between the training-induced change in MHC type I content and chair rise-time.
      These data suggest that improved function (chair rise-time) was associated with a
      lower level of MHC type I and increased MHC type IIa composition. Furthermore,
      the data are consistent with the hypothesis that creatine supplementation alters
      MHC composition in CMT patients undergoing resistance training and that MHC
      changes associated with creatine supplementation can improve muscle function.

PMID- 16881065
TI  - Exercise-induced cramp, myoglobinuria, and tubular aggregates in phosphoglycerate
      mutase deficiency.
AB  - We report two patients in whom phosphoglycerate mutase (PGAM) deficiency was
      associated with the triad of exercise-induced cramps, recurrent myoglobinuria,
      and tubular aggregates in the muscle biopsy. Serum creatine kinase (CK) levels
      were elevated between attacks of myoglobinuria. Forearm ischemic exercise tests
      produced subnormal increases of venous lactate. Muscle biopsies showed
      subsarcolemmal tubular aggregates in type 2 fibers. Muscle PGAM activities were
      markedly decreased (3% of the normal mean) and molecular genetic studies showed
      that both patients were homozygous for a described missense mutation (W78X). A
      review of 15 cases with tubular aggregates in the muscle biopsies from our
      laboratory and 15 cases with PGAM deficiency described in the literature showed
      that this clinicopathological triad is highly suggestive of PGAM deficiency.

PMID- 16881066
TI  - Peripheral nerve injuries: a retrospective survey of 456 cases.
AB  - This 16-year retrospective study reports the data on 456 consecutive patients
      with 557 peripheral nerve injuries (PNIs) between 1989 and 2004. Most patients
      were men (74%) and the mean age was 32.4 years. In 83% of cases the PNIs were
      isolated; combined lesions most commonly involved the ulnar and median nerves.
      Upper-limb PNIs occurred in 73.5% of cases; the ulnar nerve was most often
      injured, either singly or in combination. Vehicle accidents affecting the
      brachial plexus or radial, sciatic, facial, and peroneal nerves were the most
      common cause of injury. Penetrating trauma commonly affected the ulnar and median
      nerves; falls and gunshot wounds frequently affected the ulnar, radial, and
      median nerves; and sports injuries, particularly soccer, affected mainly the
      peroneal and tibial nerves. More than half of the brachial plexus lesions after
      vehicular accidents were from motorcycle crashes.

PMID- 16881067
TI  - Assessing neuromuscular disease with multifrequency electrical impedance
      myography.
AB  - Electrical impedance myography (EIM) is a noninvasive technique for neuromuscular
      assessment in which low-intensity alternating current is applied to a muscle and
      the consequent surface voltage patterns are evaluated. Previous work using a
      single frequency of 50 kHZ has demonstrated quantitative correlation of EIM
      parameters with disease status. In this investigation we examined the use of
      multifrequency EIM, studying a prototypical neurogenic disease (amyotrophic
      lateral sclerosis, ALS) and myopathic disorder (inflammatory myopathy, IM).
      Eleven ALS patients, 7 IM patients, and 46 normal subjects participated in the
      study. Although disease-specific patterns were not identified such that IM could
      be differentiated from ALS, impedance vs. frequency patterns for diseased
      subjects differed substantially from those of the age-matched normal subjects,
      with the greatest alterations occurring in the most severe cases. Multifrequency
      EIM may be well-suited to serve as an easily applied technique to assess disease
      severity in a variety of neuromuscular conditions.

PMID- 16881068
TI  - Methyl-CpG binding proteins are involved in restricting differentiation
      plasticity in neurons.
AB  - Neurons and astrocytes are generated from common neural precursors, yet
      neurogenesis precedes astrocytogenesis, which normally commences at later stages
      of development. We have previously reported that a particular cytosine residue
      within a STAT3-binding site in the astrocyte-specific marker glial fibrillary
      acidic protein (GFAP) gene promoter becomes demethylated in neuroepithelial cells
      as gestation proceeds. This demethylation correlates tightly with the onset of
      astrocyte differentiation, suggesting that a change in DNA methylation at cell
      type-specific gene promoters controls the switch from neurogenesis to
      astrocytogenesis in the developing brain. Here, we show that late-gestation
      neuroepithelial cells, which have already lost the methylation in the STAT3
      binding site within the GFAP promoter, can still give rise to neurons and that
      these neurons do not respond to a STAT3-activating cytokine to express GFAP.
      Members of a transcriptional repressor family, the methylated-CpG binding
      proteins (MBDs), including MeCP2, are predominantly expressed in neurons, and
      ectopic MeCP2 expression inhibited astrocyte differentiation of neuroepithelial
      cells. Moreover, we found that exon 1 of the GFAP gene remains hypermethylated
      even in neuroepithelial cells at a late developmental stage and in neurons
      differentiated from such neuroepithelial cells. We further demonstrate that MeCP2
      actually binds to the highly methylated exon 1 of the GFAP gene in neurons. These
      results suggest that region-specific DNA methylation and MBDs play an important
      role in the regulation of differentiation plasticity in neurons.

PMID- 16881069
TI  - Mammalian nuclear transfer.
AB  - During development, the genetic content of each cell remains, with a few
      exceptions, identical to that of the zygote. Differentiated cells, therefore,
      retain all the genetic information necessary to generate an entire organism
      (nuclear totipotency). Nuclear transfer (NT) was initially developed to test
      experimentally this concept by cloning animals from differentiated cells. It has,
      since then, been used to study the role of genetic and epigenetic alterations
      during development and disease. In this review, we highlight some of the
      milestones in mammalian NT reached in the 50 years after the first nuclear
      transplantations in frogs. We also address problems associated with mammalian
      nuclear transfer and provide a survey on current NT and stem cell technology. In
      the long term, nuclear transfer or alternative strategies aim to generate
      customized pluripotent cells, which would be invaluable to medical research and
      therapy.

PMID- 16881071
TI  - Session-long modulations of accumbal firing during sucrose-reinforced operant
      behavior.
AB  - The nucleus accumbens is involved in the selection and expression of motivated
      behaviors. Attempts to understand how activity of single neurons in the accumbens
      relates to behavior have largely concentrated on brief modulations in accumbal
      firing that occur in the seconds around events during operant sessions. However,
      a small number of studies have reported modulations that last the entire duration
      of a behavioral session. In all of these reports, the operant session was a drug
      self-administration session. The present study tested the hypothesis that session
      long modulations, like phasic firing patterns, are components of normal accumbal
      activity during periods of instrumental behavior. Eight rats were chronically
      implanted (unilaterally) with microwire arrays in the nucleus accumbens, and
      trained to lever press on a Fixed-Ratio 1 schedule of sucrose reinforcement.
      Activity of 51 single units was recorded, and both session-long increases (n =
      14) and session-long decreases (n = 13) were observed. These findings show that
      session-long modulations are a normal component of the response of accumbal
      neurons during periods of operant behavior. Moreover, although session-long
      modulations during cocaine self-administration sessions might reflect
      pharmacological actions, aspects of the modulations might additionally or
      alternatively correspond to afferent-driven responses. Further characterization
      of the firing patterns may elucidate novel mechanisms that mediate accumbal
      contributions to behavior.

PMID- 16881070
TI  - GABAA receptor regulation of voluntary ethanol drinking requires PKCepsilon.
AB  - Protein kinase C (PKC) regulates a variety of neural functions, including ion
      channel activity, neurotransmitter release, receptor desensitization and
      differentiation. We have shown previously that mice lacking the epsilon-isoform
      of PKC (PKCepsilon) self-administer 75% less ethanol and exhibit supersensitivity
      to acute ethanol and allosteric positive modulators of GABA(A) receptors when
      compared with wild-type controls. The purpose of the present study was to examine
      involvement of PKCepsilon in GABA(A) receptor regulation of voluntary ethanol
      drinking. To address this question, PKCepsilon null-mutant and wild-type control
      mice were allowed to drink ethanol (10% v/v) vs. water on a two-bottle continuous
      access protocol. The effects of diazepam (nonselective GABA(A) BZ positive
      modulator), zolpidem (GABA(A) alpha1 agonist), L-655,708 (BZ-sensitive GABA(A)
      alpha5 inverse agonist), and flumazenil (BZ antagonist) were then tested on
      ethanol drinking. Ethanol intake (grams/kg/day) by wild-type mice decreased
      significantly after diazepam or zolpidem but increased after L-655,708
      administration. Flumazenil antagonized diazepam-induced reductions in ethanol
      drinking in wild-type mice. However, ethanol intake by PKCepsilon null mice was
      not altered by any of the GABAergic compounds even though effects were seen on
      water drinking in these mice. Increased acute sensitivity to ethanol and
      diazepam, which was previously reported, was confirmed in PKCepsilon null mice.
      Thus, results of the present study show that PKCepsilon null mice do not respond
      to doses of GABA(A) BZ receptor ligands that regulate ethanol drinking by wild
      type control mice. This suggests that PKCepsilon may be required for GABA(A)
      receptor regulation of chronic ethanol drinking.

PMID- 16881072
TI  - Chronic treatment with Delta-9-tetrahydrocannabinol alters the structure of
      neurons in the nucleus accumbens shell and medial prefrontal cortex of rats.
AB  - The potential of repeated exposure to Delta(9)-tetrahydrocannabinol (Delta(9)
      THC) to produce long-lasting changes in synaptic connections in a manner similar
      to other drugs of abuse was evaluated in Sprague-Dawley rats. For 12 days, rats
      received two i.p. injections per day (8 h apart) of vehicle, a low dose of
      Delta(9)-THC (0.5 mg/kg), or escalating doses of Delta(9)-THC (0.5-4.0 mg/kg).
      Thirty days later, they were evaluated for sensitized locomotor activity (during
      the night cycle) for 60 min on each of three trials. Using a within-groups
      design, rats were tested following an injection of vehicle, 0.5 mg/kg Delta(9)
      THC or 2.0 mg/kg Delta(9)-THC. The rats showed no evidence of sensitized
      locomotor activity in any group. Twenty-four hours after the final sensitization
      test, their brains were removed and then processed for Golgi-Cox staining. Prior
      exposure to Delta(9)-THC (both the low dose and the escalating doses) increased
      the length of the dendrites as well as the number of dendritic branches in the
      shell of the nucleus accumbens and in the medial prefrontal cortex, but not in
      the hippocampus, striatum, orbital frontal cortex, parietal cortex, or occipital
      cortex. These results are similar to those evident in brains of rats sensitized
      to amphetamine, and support previous findings that cannabinoids promote DA
      activity in the mesolimbic DA system.

PMID- 16881073
TI  - Reverse optical probing (ROPING) of neocortical circuits.
AB  - We describe an optical technique to detect circuits of synaptically connected
      neurons. By combining calcium imaging of the spontaneous activity of neuronal
      populations with intracellular recordings from a given neuron, we perform a type
      of reverse correlation analysis to detect neurons that generate action potentials
      time-locked to the synaptic currents of the recorded cell. This technique can
      quickly reveal monosynaptically connected neurons.

PMID- 16881074
TI  - A comparative study of the risk of malignancy index and the ovarian crescent sign
      for the diagnosis of invasive ovarian cancer.
AB  - OBJECTIVE: To compare the value of the risk of malignancy index (RMI) and the
      ovarian crescent sign (OCS) in the diagnosis of ovarian malignancy. METHODS: This
      was a prospective observational study of women with ultrasonographic diagnosis of
      an ovarian cyst. The RMI was calculated in all cases using a previously published
      formula (RMI = U (ultrasound score) x M (menopausal status) x serum CA125
      (kU/L)). A value > 200 was considered to be diagnostic of ovarian cancer. The OCS
      was defined as a rim of visible healthy ovarian tissue in the ipsilateral ovary.
      Its absence was taken as being diagnostic of invasive cancer. RESULTS: A total of
      106 consecutive women were included in the study, of whom 92 (86.8%) had a benign
      ovarian tumor, five (4.7%) had borderline lesions and nine (8.5%) had an invasive
      ovarian cancer. The absence of an OCS diagnosed invasive ovarian cancer with a
      sensitivity of 100% (95% CI, 70-100%), specificity of 93% (95% CI, 86-96%),
      positive predictive value (PPV) of 56%, negative predictive value (NPV) of 100%
      and positive likelihood ratio (LR+) of 13.86 (95% CI, 6.79-28.29). This compared
      favorably with a sensitivity of 89% (95% CI, 57-98%), specificity of 92% (95% CI,
      85-96%), PPV of 50%, NPV of 99% and LR+ of 10.78 (95% CI, 5.34-21.77), which were
      achieved using RMI > 200 (P < 0.01). CONCLUSIONS: The RMI and the OCS are useful
      tests for discriminating between invasive and non-invasive ovarian tumors. The
      application of these tests in a sequential manner might improve the overall
      accuracy of ovarian cancer diagnosis.

PMID- 16881075
TI  - Macroscopic properties of spontaneous mutations in slow-channel syndrome:
      correlation by domain and disease severity.
AB  - The slow-channel syndrome (SCS) is a neuromuscular disorder characterized by
      fatigability, progressive weakness, and degeneration of the neuromuscular
      junction. The SCS is caused by missense mutations in the four subunits of the
      skeletal muscle acetylcholine receptor (AChR), which leads to altered channel
      gating, prolonged neuromuscular postsynaptic currents, and impaired neuromuscular
      transmission. Although a diverse set of mutations in different functional domains
      of the AChR appear to be associated with symptoms of widely ranging severity,
      there is as yet no mutant channel property or combination that explains the
      variations in disease severity. By observing the recovery time of AChR from
      desensitization, the authors determined that this process is significantly
      enhanced in SCS channels. In addition, as expected, the authors found that SCS
      macroscopic decay currents in transfected HEK293 cells are slower than wild type
      currents. While slight differences in relative Ca(2+) permeability between some
      SCS mutations were identified, they did not correlate with apparent disease
      severity. These results suggest that of the different AChR kinetic features
      studied, only recovery from desensitization and slow postsynaptic currents
      correlate with the severity observed in the different mutations of this syndrome.

PMID- 16881076
TI  - A comparative investigation of the thermal unfolding of pseudoazurin in the
      Cu(II)-holo and apo form.
AB  - The contribution of the copper ion to the stability and to the unfolding pathway
      of pseudoazurin was investigated by a comparative analysis of the thermal
      unfolding of the Cu(II)-holo and apo form of the protein. The unfolding has been
      followed by calorimetry, fluorescence, optical density, and electron paramagnetic
      resonance (EPR) spectroscopy. The thermal transition of Cu(II)-holo pseudoazurin
      is irreversible and occurs between 60.0 and 67.3 degrees C, depending on the scan
      rate and technique used. The denaturation pathway of Cu(II)-holo pseudoazurin can
      be described by the Lumry-Eyring model: N --> U --> [corrected] F; the protein
      reversibly goes from the native (N) to the unfolded (U) state, and then
      irreversibly to the final (F) state. The simulation of the experimental
      calorimetric profiles, according to this model, allowed us to determine the
      thermodynamic and kinetic parameters of the two steps. The DeltaG value
      calculated for the Cu(II)-holo pseudoazurin is 39.2 kJ.mol(-1) at 25 degrees C.
      The sequence of events in the denaturation process of Cu(II)-holo pseudoazurin
      emergence starts with the disruption of the copper site and the hydrophobic core
      destabilization followed by the global protein unfolding. According to the EPR
      findings, the native type-1 copper ion shows type-2 copper features after the
      denaturation. The removal of the copper ion (apo form) significantly reduces the
      stability of the protein as evidenced by a DeltaG value of 16.5 kJ.mol(-1) at 25
      degrees C. Moreover, the apo Paz unfolding occurs at 41.8 degrees C and is
      compatible with a two-state reversible process N --> [corrected] U.

PMID- 16881077
TI  - Malignant peripheral nerve sheath tumors: prognostic factors and survival in a
      series of patients treated at a single institution.
AB  - BACKGROUND: The authors explored the prognostic factors and clinical outcomes of
      patients who had malignant peripheral nerve sheath tumors (MPNST) with and
      without neurofibromatosis type 1 (NF-1). METHODS: Two hundred five patients with
      localized MPNST who underwent surgery at the Istituto Nazionale per lo Studio e
      la Cura dei Tumori (Milan, Italy) over 25 years were reviewed. Forty-six patients
      had concomitant NF-1 syndrome, and 159 patients did not. Local recurrence,
      distant metastases, and survival rates were studied. RESULTS: One hundred thirty
      patients presented with primary disease, and 75 patients had locally recurrent
      tumors. The disease-specific mortality rate was 43% at 10 years, with a
      continuously disease-free survival rate of no greater than 40%. Presentation with
      either primary or recurrent disease, tumor size, and tumor site (trunk vs.
      extremity) were the strongest independent predictors of survival. Margin status
      and radiation therapy also played a role, mostly related to their effect on local
      outcome. Pathologic grade influenced distant metastases, but only a trend for
      survival could be observed. No significant independent differences between
      patients with and without NF-1 were observed. CONCLUSIONS: To the authors'
      knowledge, this was among the largest single-institution series to date. The
      results confirmed that patients with MPNST share similar prognostic factors with
      patients who have other soft tissue sarcomas and have some of the worst clinical
      outcomes. The presence of NF-1 syndrome per se did not affect survival, but
      patients with NF-1 were more likely to have larger tumors. Therefore, such
      patients should be followed carefully to detect disease as early as possible.

PMID- 16881078
TI  - Family history of breast cancer as a risk factor for ovarian cancer in a
      prospective study.
AB  - BACKGROUND: A family history of breast cancer has been associated with increased
      ovarian cancer risk. However, few studies have assessed risk according to
      characteristics that suggest an inherited cancer susceptibility disorder, such as
      earlier-than-usual age at cancer diagnosis, family members with double primary
      cancers of different types, multiple relatives with cancer, and cancer in both
      members of paired organs. METHODS: Ovarian cancer risk was assessed according to
      a detailed breast cancer family history among 49,975 participants in the Breast
      Cancer Detection Demonstration Project Breast Cancer Defection Demenstration
      Project (BCDDP) Follow-up Study (1979-1998). In all, 362 incident ovarian cancers
      were identified during follow-up and rate ratios (RRs) were calculated by Poisson
      regression. RESULTS.: Breast cancer in a first- or second-degree relative was
      associated with increased risk of ovarian cancer (RR = 1.4; 95% confidence
      interval [CI] = 1.1-1.7). Having 2 or more affected first-degree relatives was
      associated with increased risk (RR = 1.8; 95% CI = 1.1-2.8), especially for women
      diagnosed with ovarian cancer before age 60 (RR = 4.2; 95% CI = 1.9-9.2) or with
      a personal history of breast cancer (RR = 3.7; 95% CI 1.8-7.7). Risk was also
      particularly high for women with 2 or more first-degree relatives with breast
      cancer and at least 1 affected relative diagnosed before age 50 (RR = 2.6; 95% CI
      = 1.4-4.8) or with bilateral breast cancer (RR = 4.2; 95% CI = 1.7-10).
      CONCLUSIONS: A detailed breast cancer family history as well as an individual's
      age and personal history of breast cancer are useful for identifying women at
      elevated genetic risk of ovarian cancer.

PMID- 16881079
TI  - Evolution of declarative memory.
AB  - The present review considers research on the hippocampus and related areas from
      humans and experimental animals and makes three main points. First, many of the
      anatomical details of the hippocampus and adjacent cortical areas in the
      parahippocampal region are conserved across mammals. Second, the functional role
      of these areas in declarative memory is also conserved across species. Third, an
      evolutionary approach will be key to understanding exactly how the local
      circuitry of the hippocampus and parahippocampal region supports declarative
      memory. To highlight the utility of this approach, a schematic model is described
      in which separate streams of spatial and nonspatial information converge on the
      hippocampus. By this view, a fundamental function of the mammalian hippocampus is
      to combine incoming information about spatial context from the postrhinal
      (parahippocampal in primates) cortex and medial entorhinal area with incoming
      information about nonspatial items from the perirhinal cortex and lateral
      entorhinal area. The underlying neurobiological computations that arise from
      local circuitry enable item-in-context memory and are proposed to be fundamental
      to many examples of declarative memory, including episodic memory in humans and
      spatial memory in experimental animals.

PMID- 16881080
TI  - Hippocampal place fields: a neural code for episodic memory?

PMID- 16881081
TI  - Synthesis of functionalized guanidino amino acids.
AB  - We report the synthesis of guanidino amino acids (GuAA), which are structurally
      related to Arg and resemble a dipeptide consisting of alpha- and gamma-amino acid
      with a guanidinium group in the main chain. The compounds are available with
      different protecting groups in gram amounts and are intended as synthetic
      building blocks for the construction of synthetic oxoanion or peptide receptors.
      Tyr, Trp or dansyl-functionalized Lys can be introduced as the alpha-amino acid
      part, which leads to luminescent GuAAs. The compounds signal carboxylate binding
      in MeOH, DMSO and buffered water by change of the emission intensity. The
      property may find use in the construction of chemosensors.

PMID- 16881082
TI  - CO combustion on supported gold clusters.
AB  - Recent progress in the understanding of the fascinating catalysis of CO
      combustion by supported gold particles is summarized. Focusing on size-selected
      gold clusters consisting of only a few atoms, that is, the size regime with
      properties nonscalable from the bulk properties, we discuss the current knowledge
      of the different factors controlling the reactivity at the molecular level. These
      factors include the role of the oxide support, its defects, cluster charging as
      well as the structural fluxionality of clusters, the cluster size dependency, and
      the promotional effect of water. By combining experimental results with quantum
      mechanical ab initio calculations, a detailed picture of the reaction mechanism
      emerges. While similar mechanisms might be active for gold nanoparticles in the
      scalable size regime, it is shown that for different systems (defined by the
      cluster size, the support, experimental conditions, etc.) the reaction mechanism
      differs and, hence, no generalized explanation for the catalytic driving force of
      small gold particles can be given.

PMID- 16881083
TI  - Ion-pair formation in the ionic liquid 1-ethyl-3-methylimidazolium
      bis(triflyl)imide as a function of temperature and concentration.
AB  - The structures and ion-pair formation in the ionic liquid (IL) 1-ethyl-3
      methylimidazolium bis(trifluoromethylsulfonyl)imide are studied by a combination
      of FTIR measurements and DFT calculations. We could clearly distinguish
      imidazolium cations that are completely H-bonded to anions from those that are
      single H-bonded in ion pairs. Ion-pair formation already occurs in the neat IL
      and rises with temperature. Ion-pair formation is strongly promoted by dilution
      of the IL in chloroform. In these weakly polar environments ion pairs H-bonded
      via C(2)H are strongly favored over those H-bonded via C(4,5)H. This finding is
      in agreement with DFT (gas phase) calculations, which show a preference for ion
      pairs H-bonded via C(2)H as a result of the acidic C(2)H bond.

PMID- 16881084
TI  - Acidity function of water-in-oil microemulsions.

PMID- 16881085
TI  - Spontaneous vesicle formation of an industrial single-chain surfactant at acidic
      pH and at room-temperature.

PMID- 16881086
TI  - Shape and magnetic properties of single-crystalline hematite (alpha-Fe2O3)
      nanocrystals.

PMID- 16881087
TI  - Oxidation and reduction of mass-selected Au clusters on SiO2/Si.

PMID- 16881088
TI  - On the role of oxygen in stabilizing low-coordinated Au atoms.

PMID- 16881089
TI  - Non-covalent interactions in polysaccharide systems.
AB  - [Chemical structure: see text] This paper describes the behavior of some
      polysaccharides with well-known chemical structures and in which the influence of
      cooperative secondary interactions play an important role. The roles played by
      hydrophobic and ionic interactions (including ionic selectivity) on
      polysaccharide conformation and gelation are discussed. Electrostatic attractions
      are also important in the complexes formed between surfactants and
      polyelectrolytes of opposite charge. Finally, van der Waals dipolar interactions
      and particularly hydrogen-bond formation are examined. The role of hydrogen bonds
      in solubility, conformation, and especially the local stiffness of
      polysaccharides, but also in polymer-polymer complexes frequently obtained with
      polysaccharides, is developed. Repeat unit for a number polysaccharides.

PMID- 16881090
TI  - Merging organic and polymer chemistries to create glycomaterials for glycomics
      applications.
AB  - [Image: see text] Oligosaccharides at cell surfaces are known to play a critical
      role in many biological processes such as biorecognition, interactions between
      cells and with artificial surfaces, immune response, infection and inflammation.
      In order to facilitate studies of the role of sugars, an increasing number of
      novel tools are becoming available. New synthetic strategies now provide much
      more efficient access to complex carbohydrates or glycoconjugates. Branched
      carbohydrates and hybrids of carbohydrates conjugated to polymers have been
      prepared using solution and/or solid-phase synthesis and advanced methods of
      polymerization. These materials are essential for the development of
      methodologies to study and map the molecular structure-function relationship at
      interfaces. This article highlights recent advances in the synthesis of
      carbohydrates and polymer hybrids mimicking the properties and functionalities of
      the natural oligosaccharides, as well as selected applications in biology,
      biotechnology and diagnostics.

PMID- 16881092
TI  - Monitoring oral anticoagulation may require determination of single coagulation
      factor activities in patients with antiphospholipid syndrome.
AB  - We describe a 32-year-old man with secondary antiphospholipid syndrome (APS) who
      received oral anticoagulation with phenprocoumon after deep vein thrombosis.
      Conventional monitoring of oral anticoagulation by INR measurement was impaired
      by coagulation factor inhibition in vitro due to a strong lupus anticoagulant.
      The case illustrates that monitoring of oral anticoagulation may require
      determination of single coagulation factor activities in selected patients with
      APS.

PMID- 16881093
TI  - Is there a role for arthroscopic synovectomy in oligoarticular juvenile
      idiopathic arthritis?
AB  - OBJECTIVE: To evaluate the longterm efficacy and safety of arthroscopic
      synovectomy (AS) in children with oligoarticular juvenile idiopathic arthritis
      (JIA). METHODS: Patients with oligoarticular JIA and persistent monoarticular
      involvement, refractory to nonsteroidal antiinflammatory drugs (NSAID) and/or
      intraarticular corticosteroid (IAC) treatment underwent AS followed, one month
      later, by IAC. The efficacy of AS was prospectively evaluated, and a good
      response was defined as absence of synovitis or > or = 60% decrease in articular
      score from baseline. Clinical, laboratory, and radiological variables
      (radiographs, ultrasound, magnetic resonance imaging) were noted to examine
      possible factors predictive of the result. RESULTS: Twenty-two patients with JIA
      (15 female, 7 male) entered the study. Age at disease onset was 77 months (range
      13-168). Mean disease duration at the time of AS was 50 months (3-324). Nineteen
      knees, 2 temporomandibular joints, and one shoulder were treated; the mean
      followup was 57 months (12-168). Thirty-six percent of patients relapsed within
      12 months of the procedure, 14% within 24 months, and 14% thereafter. Eight
      patients (36%) remain in remission after a mean 65 months' followup. Variables
      found to be predictive of good response were persistent monoarticular course (p =
      0.004), short disease duration at the time of AS (p = 0.03), and normal
      erythrocyte sedimentation rate and C-reactive protein at baseline (p = 0.008 and
      0.01, respectively). CONCLUSION: AS is a safe but only partially effective
      procedure in patients with oligoarticular JIA. Best results are achieved early in
      the disease course in children with persistent monoarticular involvement and no
      evidence of systemic inflammation.

PMID- 16881094
TI  - Workplace, psychosocial factors, and depressive symptoms among working people
      with arthritis: a longitudinal study.
AB  - OBJECTIVE: To examine the role of demographic, illness-related, workplace
      support, workplace activity limitations, arthritis-related work changes, and
      psychosocial factors in predicting subsequent depressive symptoms among employed
      people with arthritis. METHODS: In a prospective study, 366 employed individuals
      with arthritis were recruited from Toronto, Canada. Respondents completed a
      structured questionnaire assessing demographic, disease-related factors,
      workplace support, and employment-related transitions, as well as psychosocial
      variables at 2 timepoints 18 months apart. Depression was assessed using the
      Center for Epidemiologic Studies Depression Scale. Hierarchical multiple
      regression was used for analyses. RESULTS: Individuals with greater education
      reported significantly less depression. Lower workplace support and greater
      workplace activity limitations were significantly associated with future
      depressive symptoms. No relationship was found between work transitions and later
      depression, but more work changes were strongly associated with concurrent
      depressive symptoms. An association was also found between greater pain
      catastrophizing and future depressive symptoms. CONCLUSION: Our results highlight
      the need to assess the influence of work-related changes, workplace support, and
      psychosocial variables on depressive symptoms among people with arthritis. These
      findings suggest that workplace interventions should address not only ways to
      reduce workplace activity limitations, but also ways to better manage emotional
      distress related to working with arthritis.

PMID- 16881095
TI  - Lateral epicondylitis in general practice: course and prognostic indicators of
      outcome.
AB  - OBJECTIVE: To investigate the course of lateral epicondylitis and identify
      prognostic indicators associated with short- and longterm outcome of pain
      intensity. METHODS: We prospectively followed patients (n = 349) from 2
      randomized controlled trials investigating conservative interventions for lateral
      epicondylitis in primary care. Uni- and multivariate linear regression analyses
      were used to investigate the association between potential prognostic indicators
      and pain intensity (0-100 point scale) measured at 1, 6, and 12 months after
      randomization. Potential prognostic factors were duration of elbow complaints,
      concomitant neck pain, concomitant shoulder pain, previous elbow complaints,
      baseline pain scores, age, gender, involvement of dominant side, social class,
      and work status. The variables "study" and "treatment" were included as
      covariates in all models. RESULTS: Pain scores at 1 month followup were higher in
      patients with severe pain, a long duration of elbow complaints, and concomitant
      shoulder pain. At 12 month followup, the only different prognostic indicator for
      poor outcome was concomitant neck pain, in place of shoulder pain. Patients from
      higher social classes reported lower pain scores at 12 month followup than
      patients from lower social classes. CONCLUSIONS: Lateral epicondylitis seems to
      be a self-limiting condition in most patients. Long duration of elbow complaints,
      concomitant neck pain, and severe pain at presentation are associated with poor
      outcome at 12 months. Our results will help care providers give patients accurate
      information regarding their prognosis and assist in medical decision-making.

PMID- 16881096
TI  - The relationship between prospectively assessed body weight and physical activity
      and prevalence of radiological knee osteoarthritis in postmenopausal women.
AB  - OBJECTIVE: To determine the effect of weight and physical activity on the
      prevalence of radiological knee osteoarthritis (OA) in a cohort of middle-aged
      women. METHODS: The longitudinal phase of the Melbourne Women's Mid-life Health
      Project is a population-based prospective study of 438 Australian-born women who
      have been followed annually over 11 years. Of these women, 257 (59%) remained in
      longitudinal assessment at eleventh year of followup, and 224 of these women
      agreed to undergo radiographs of their knees. Radiographs were scored for
      features of OA [osteophytes and joint space narrowing (JSN)] using a validated
      scale, by 2 investigators who were blinded to questionnaire results. Data were
      obtained by both self-administered and face-to-face interview questionnaires.
      RESULTS: The average weight increase over the study period of 11 years was 4 kg
      (range -14 to 25 kg). Of the 224 women evaluated, 65 (29%) had knee joint
      osteophytes and 95 (42%) had evidence of knee JSN. Current weight and weight at
      baseline were independent factors associated with a higher prevalence of both
      osteophytes and JSN in all compartments of the knee. The average amount of
      physical activity over the 11 years of followup was a significant factor
      independently associated with an increased prevalence of patellofemoral JSN and
      approached significance for tibiofemoral osteophytes and total knee JSN.
      CONCLUSION: Our study supports a longterm detrimental effect of weight on the
      knee joint and suggests the importance of longterm weight maintenance programs in
      preventing knee OA. The average amount of physical activity was associated with
      an increased prevalence of some features of knee OA.

PMID- 16881098
TI  - Magnetic resonance imaging is more sensitive than radiographs in detecting change
      in size of erosions in rheumatoid arthritis.
AB  - OBJECTIVE: To evaluate the technological performance of magnetic resonance
      imaging (MRI) with respect to projection radiography by determining the incidence
      of changes in the size of individual bone lesions in inflammatory arthritis,
      using serial high-resolution in-office MRI over short time intervals (8 months
      average followup), and by comparing the sensitivity of 3-view projection
      radiography with in-office MRI for detecting changes in size and number of
      individual erosions. METHODS: MR examinations of the wrists and second and third
      metacarpophalangeal joints were performed using a portable in-office MR system in
      a total of 405 patients with inflammatory arthritis, from one rheumatologist's
      practice, who were undergoing aggressive disease modifying antirheumatic drug
      therapy. Of the patients, 156 were imaged at least twice, allowing evaluation of
      246 followup examinations (mean followup interval of 8 months over a 2-year
      period). Baseline and followup plain radiographs were obtained in 165 patient
      intervals. Patients refused radiographic examination on 81 followup visits.
      RESULTS: MRI demonstrated no detectable changes in 124 of the 246 (50%) followup
      MRI examinations. An increase in the size or number of erosions was demonstrated
      in 74 (30%) examinations, a decrease in the size or number of erosions in 36
      (15%), and both increases and decreases in erosions were seen in 11 (4%). In the
      165 studies with followup radiographic comparisons, only one examination (0.8%)
      showed an erosion not seen on the prior examination and one (0.8%) showed an
      increase in a previously noted erosion. CONCLUSION: We showed that high
      resolution in-office MRI with an average followup of 8 months detects changes in
      bony disease in 50% of compliant patients during aggressive treatment for
      inflammatory arthritis in a single rheumatologist's office practice. Plain
      radiography is insensitive for detecting changes in bone erosions for this
      patient population in this time frame.

PMID- 16881099
TI  - Mortality in patients with rheumatoid arthritis treated with low-dose oral
      glucocorticoids. A population-based cohort study.
AB  - OBJECTIVE: To evaluate mortality and causes of death in patients with rheumatoid
      arthritis (RA) treated with low-dose oral glucocorticoids. METHODS: Mortality was
      analyzed in population-based data of 604 patients with RA. In the original study
      in 1988, state of general health, severity of RA, and treatment including the use
      of oral glucocorticoids were recorded. In 1999 vital status and causes of death
      were evaluated. Mortality in patients with RA who had not received
      glucocorticoids (Group A, n = 209) was compared to that in patients treated with
      glucocorticoids for less than 10 years (Group B, n = 276) or for more than 10
      years (Group C, n = 119). RESULTS: From onset of RA to 1999, 395 (65%) patients
      had been treated with oral glucocorticoids. In 1999 a total of 160 (26%) patients
      had died, 23% of patients in Group A, 21% in Group B, and 45% in Group C. In
      multivariate Cox regression analysis, male sex (hazard ratio 2.50; 95% CI 1.74
      3.59), impaired functional capacity by Health Assessment Questionnaire (HR 2.11;
      95% CI 1.65-2.96), heart failure (HR 1.96; 95% CI 1.36-2.84), and diabetes (HR
      1.87; 95% CI 1.17-3.01) predicted increased mortality. In the same analysis
      glucocorticoid treatment for 1 year increased the mortality risk by 14% (HR 1.14;
      95% CI 0.98-1.27, p = 0.057) and treatment over 10 years by 69% (HR 1.69; 95% CI
      1.12-2.56, p = 0.011) compared to RA patients without treatment. The major cause
      of death was cardiovascular disease in all groups, but infections and intestinal
      perforations due to amyloidosis were more frequent in patients with long-lasting
      glucocorticoid therapy. Lymphomas were more frequent in all patients treated with
      glucocorticoids (Groups B and C) than in those not receiving glucocorticoids.
      CONCLUSION: Patients with RA treated with low-dose oral glucocorticoids for more
      than 10 years had increased mortality compared to those who did not receive
      glucocorticoids or whose duration of treatment was less than 10 years. The
      increased mortality was related mainly to infections and complications caused by
      systemic amyloidosis.

PMID- 16881100
TI  - Reduction of cardiovascular risk factors with longterm fish oil treatment in
      early rheumatoid arthritis.
AB  - OBJECTIVE: Rheumatoid arthritis (RA) is associated with increased risk for
      cardiovascular (CV) events through multiple factors. Fish oil has been shown to
      reduce symptoms in RA and to reduce CV risk. We assessed the effect of an
      antiinflammatory dose of fish oil on CV risk factors within a program of
      combination chemotherapy for patients with early RA. METHODS: Patients who chose
      not to take fish oil (n = 13) were compared with patients who achieved a
      sustained elevation of eicosapentaenoic acid (EPA) in plasma phospholipid fatty
      acids (> 5% total fatty acids) while taking fish oil over a 3-year period (n =
      18). We examined cellular content of arachidonic acid (AA), synthesis of
      thromboxane A2 and prostaglandin E2, use of nonsteroidal antiinflammatory drugs
      (NSAID), traditional CV lipid risk factors, and disease activity at 3 years.
      RESULTS: At 3 years, AA (as a proportion of AA plus long-chain n-3 fatty acids
      that can compete with AA for cyclooxygenase metabolism) was 30% lower in
      platelets and 40% lower in peripheral blood mononuclear cells in subjects taking
      fish oil. Serum thromboxane B2 was 35% lower and lipopolysaccharide-stimulated
      whole-blood prostaglandin E2 was 41% lower with fish oil ingestion compared to no
      fish oil. NSAID use was reduced by 75% from baseline with fish oil (p < 0.05) and
      by 37% without fish oil (NS). Favorable changes in fasting blood lipids were seen
      with, but not without fish oil. Remission at 3 years was more frequent with fish
      oil use (72%) compared to no fish oil (31%). CONCLUSION: Fish oil reduces
      cardiovascular risk in patients with RA through multiple mechanisms.

PMID- 16881101
TI  - Prevention of glucocorticoid-induced osteoporosis: why are we doing so poorly?

PMID- 16881102
TI  - Early diagnosis and treatment in lupus nephritis: how we can influence the risk
      for terminal renal failure.

PMID- 16881103
TI  - Anemia of chronic disease in patients with rheumatoid arthritis: aspects of
      prevalence, outcome, diagnosis, and the effect of treatment on disease activity.

PMID- 16881104
TI  - Why have rheumatologists been reluctant to vaccinate patients with systemic lupus
      erythematosus?

PMID- 16881105
TI  - Frequency of osteoporosis in 187 men with rheumatoid arthritis followed in a
      university hospital.
AB  - OBJECTIVE: Although there is relevant information on frequency of osteoporosis in
      women with rheumatoid arthritis (RA), data about male patients are limited. We
      evaluated the frequency of osteoporosis in a group of Spanish men with RA
      followed in a university hospital. METHODS: From the database of our bone
      densitometry unit, we searched for men with RA evaluated between January 1991 and
      December 2004 and identified 187 patients, 156 of whom were older than 50 years.
      Previously recorded demographic, disease, and treatment-related variables were
      collected. Bone mineral density (BMD) was measured by dual x-ray absorptiometry
      (DEXA). Osteoporosis was defined according to the criteria of the World Health
      Organization (WHO), recommended for postmenopausal Caucasian women, as a T score
      <or= -2.5 SD, and the International Society for Clinical Densitometry (ISCD),
      which indicates the same diagnostic threshold, but only in men over age 50 years.
      RESULTS: BMD was lower than in the general population in both lumbar spine [Z
      score -0.41 +/- 1.00 (95% CI -0.55 to -0.26)] and femoral neck [Z score -0.46 +/-
      0.95 (95% CI -0.60 to -0.31)]. When the WHO threshold for postmenopausal women
      was applied, frequency of osteoporosis was 13% at lumbar spine, 12% at the
      femoral neck, and 21% in at least one of the evaluated sites. When ISCD criteria
      were applied, the frequency of osteoporosis was 13%, 14%, and 23%, respectively.
      CONCLUSION: Frequency of osteoporosis in men is considerably lower than that
      traditionally established in women with RA, independent of the diagnostic
      criteria applied.

PMID- 16881106
TI  - Anti-cyclic citrullinated peptide versus anti-Sa antibodies in diagnosis of
      rheumatoid arthritis in an outpatient clinic for connective tissue disease and
      spondyloarthritis.
AB  - OBJECTIVE: . To compare the diagnostic value of anti-cyclic citrullinated peptide
      (anti-CCP) and anti-Sa antibodies in serum for prediction of rheumatoid arthritis
      (RA) in an outpatient clinic for connective tissue diseases and
      spondyloarthritides. METHODS: A cross-sectional study was carried out to analyze
      the presence or absence of anti-CCP and anti-Sa antibodies in the sera of 250
      randomly selected patients. The disease distribution in the study was as follows:
      87 patients had RA (34.8%); 90 (36%) had other connective tissue diseases (CTD);
      50 (20%) spondyloarthritis; 19 (7.6%) polymyalgia rheumatica; and 4 (1.6%)
      juvenile idiopathic arthritis. RESULTS: Anti-CCP antibodies were detected in 63
      patients with RA and in 9 patients with other illnesses [sensitivity 72.4%,
      specificity 94.4%, positive predictive value (PPV) 87.5%]. Anti-Sa antibodies
      were detected in 38 patients with RA and in 6 patients with other illnesses
      (sensitivity 43.6%, specificity 96.3%, PPV 86.3%). Anti-CCP and anti-Sa results
      were discordant in up to 47 of 87 RA patients. No relation between the presence
      of anti-Sa and higher or lower titers of anti-CCP antibodies was observed.
      CONCLUSION: The diagnostic value in RA is similar for both antibodies. However,
      the sensitivity of anti-CCP detection is higher than that of anti-Sa. Our results
      suggest that presence of anti-Sa antibodies in serum may be useful as a
      complementary assay when anti-CCP antibodies are negative and RA is suspected.

PMID- 16881107
TI  - Two distinct clinical courses of renal involvement in rheumatoid patients with AA
      amyloidosis.
AB  - OBJECTIVE: We conducted a prospective study to investigate whether a correlation
      exists between the clinical course of renal involvement and the pathological
      findings of renal amyloidosis in patients with rheumatoid arthritis (RA).
      METHODS: Patients with RA of more than 5 years' duration and who did not show
      renal manifestations were selected and received a duodenal biopsy for the
      diagnosis of amyloidosis. After the diagnosis of AA amyloidosis, patients
      received a renal biopsy, and patterns of amyloid deposition were examined. We
      followed the renal functions (serum levels of blood urea nitrogen and creatinine)
      of patients diagnosed with AA amyloidosis for 5 years. RESULTS: We diagnosed 53
      patients with AA amyloidosis and monitored the renal function of 38 of them for >
      5 years. The histological patterns were examined; in the 38 patients there were
      appreciable variations in the patterns of amyloid deposition. In 27 patients,
      amyloid deposits were found exclusively in the glomerulus (type 1). In the other
      11 patients, however, amyloid deposits were found selectively around blood
      vessels and were totally absent in the glomerulus (type 2). In type 1 patients
      with glomerular involvement, renal function deteriorated rapidly regardless of
      disease state; most patients received hemodialysis. In type 2 patients with
      purely vascular involvement, however, renal function did not deteriorate
      significantly. CONCLUSION: In patients with RA and AA amyloidosis, 2 distinct
      clinical courses in terms of renal involvement were identified. It is suggested
      that renal function does not deteriorate when amyloid deposition is totally
      lacking in the glomerulus.

PMID- 16881108
TI  - Anemia and renal function in patients with rheumatoid arthritis.
AB  - OBJECTIVE: Treatments are now available that can improve the anemia of chronic
      illnesses such as rheumatoid arthritis (RA). Despite recognition that anemia is
      common in RA and that renal function may be impaired and affect hemoglobin
      levels, there are almost no quantitative comparative data regarding the
      prevalence of anemia or decreased renal function in RA. METHODS: We studied a
      prospectively acquired clinical database of 2,120 patients with RA who had 26,221
      hemoglobin determinations, and a control population of 7,124 patients with
      noninflammatory rheumatic disorders (NIRD) who had 12,086 determinations.
      RESULTS: Using the World Health Organization definition, anemia occurred in 31.5%
      of patients with RA, and followed a U-shaped distribution that had minimal
      prevalence around 60 years of age. Anemia prevalence in men was 30.4% and in
      women 32.0%. Anemia occurred in 11.1% at hemoglobin < 11 g/dl and 3.4% at
      hemoglobin < 10 g/dl. After erythrocyte sedimentation rate (ESR), C-reactive
      protein (CRP) was the strongest predictor of anemia, followed by estimated
      creatinine clearance. Adjusted for age and sex, estimated creatinine clearance
      was 9.8 (95% CI 7.5 to 12.1) ml/min lower in patients with RA than in those with
      NIRD. CONCLUSION: Anemia occurs in 31.5% of RA patients, 3 times the rate in the
      general population. However, severe chronic anemia (hemoglobin < 10 g/dl) is rare
      (3.4%). In addition, renal function is impaired in patients with RA compared with
      NIRD. Renal function has a small effect on the anemia of RA, and ESR and CRP have
      slightly greater effects.

PMID- 16881109
TI  - Serum matrix metalloproteinases and tissue inhibitors of metalloproteinases in
      patients with early rheumatoid arthritis.
AB  - OBJECTIVE: To analyze serum concentrations of matrix metalloproteinases (MMP) MMP
      1, MMP-3, MMP-9, MMP-13, tissue inhibitors of MMP (TIMP) TIMP-1 and TIMP-2, and
      MMP/TIMP ratios in patients with early rheumatoid arthritis (RA) before and after
      6 months of treatment with methotrexate (MTX). METHODS: The study group consisted
      of 30 patients with RA, not treated with disease modifying antirheumatic drugs or
      corticosteroids, with disease duration < 3 years. Twenty patients with
      osteoarthritis (OA) served as a control group. Analysis of serum concentrations
      of MMP and TIMP was based on a quantitative sandwich ELISA. RESULTS: Serum
      concentrations of MMP-1, MMP-3, MMP-9, and MMP-13 were higher in untreated
      patients with early RA than in OA patients (p < 0.001 in all cases). Serum levels
      of TIMP-1 and TIMP-2 dominated in the serum of RA patients compared with controls
      (p < 0.01 and p < 0.05, respectively). Ratios of MMP to TIMP were significantly
      higher in patients with early RA versus controls. Six months' treatment with MTX
      downregulated serum concentrations of MMP-1 (p < 0.001), MMP-3 (p < 0.001), MMP-9
      (p < 0.001), MMP-13 (p < 0.01), and TIMP-1 (p < 0.05) in patients with RA. These
      changes were accompanied by significantly reduced ratios of MMP to TIMP. MTX
      treatment decreased markers of RA activity such as the number of painful and
      swollen joints, erythrocyte sedimentation rate, Disease Activity Score, and C
      reactive protein. CONCLUSION: Patients with early RA are characterized by high
      serum concentrations of tissue-degrading metalloproteinases. Therapy with MTX
      resulted in clinical improvement and reduced serum MMP levels in patients with
      RA, confirming effectiveness of MTX in patients in early stages of the disease.

PMID- 16881110
TI  - Hypothalamic-pituitary-adrenal hormonal responses to exercise stress test in
      patients with rheumatoid arthritis compared to healthy controls.
AB  - OBJECTIVE: There is controversy about hormonal dysfunction in the hypothalamic
      pituitary-adrenal (HPA) axis that is supposed to contribute to the development or
      persistence of rheumatoid arthritis (RA). We investigated whether there is an
      altered and blunted response of the HPA axis when stimulated by exercise stress
      in patients with RA. METHODS: Twenty women with RA and 15 matched healthy
      controls were included in the study. All subjects took an ergospirometric
      exercise test on the treadmill to determine anaerobic threshold (AT). On another
      day, blood was collected for basal plasma levels of growth hormone (GH), insulin
      like growth factor-I, cortisol, and adrenocorticotrophic hormone (ACTH); and
      subjects exercised on treadmill at an intensity above their AT. Blood was
      collected again to measure hormone levels just after the exercise stopped and 60
      minutes later. RESULTS: Two subjects left the study, so 19 patients and 14
      controls were evaluated. Peak oxygen consumption (VO(2)), VO(2) at AT, exercise
      test duration, and basal hormone levels were similar in groups. In both groups,
      GH slightly increased just after the exercise (0 min), and decreased at 60 min
      compared to baseline, but the change was not different between groups. Cortisol
      levels decreased significantly at 0 and 60 min in both groups, ACTH levels did
      not change in time, and there was no difference between groups. CONCLUSION: There
      was no perturbation in HPA axis stimulated by exercise stress test in patients
      with RA and all the variables measured were similar to those of the control
      group.

PMID- 16881111
TI  - Altered levels of adipocytokines in association with insulin resistance in
      patients with systemic lupus erythematosus.
AB  - OBJECTIVE: The metabolic syndrome, closely associated with cardiovascular
      disease, is characterized by increased insulin resistance (IR). Although
      accelerated atherosclerosis is frequently observed in systemic lupus
      erythematosus (SLE), the prevalence and significance of IR remain to be
      elucidated. We evaluated IR in association with plasma concentrations of
      adipocytokines in patients with SLE. METHODS: Outpatients with SLE (n = 37) and
      healthy controls (n = 80) were studied. A value of the homeostasis model
      assessment index (HOMA-IR) > 2.0 was considered to be IR. Plasma concentrations
      of adiponectin and tumor necrosis factor-a (TNF-a) were measured by ELISA and
      leptin by radioimmunoassay. RESULTS: HOMA-IR indices of the SLE patients were
      significantly higher than those of controls (2.3 +/- 2.3 vs 1.3 +/- 1.0,
      respectively; p < 0.01), although both groups exhibited a similar body mass
      index. The prevalence of hypertension and diabetes mellitus was significantly
      higher in patients with SLE compared with controls (48.6% vs 8.8% and 10.8% vs
      0%). Twelve SLE patients (32%) with IR exhibited significantly higher incidence
      of hypertension and current proteinuria than SLE patients without IR. Plasma
      leptin, TNF-a, and, unexpectedly, adiponectin levels were higher in SLE patients
      than controls (adiponectin, 13.7 +/- 5.0 vs 9.5 +/- 3.9 microg/ml). Among the SLE
      patients, patients with IR showed significantly lower adiponectin levels than
      patients without IR (10.9 +/- 4.6 vs 15.4 +/- 4.4 microg/ml). Serum levels of
      adiponectin were significantly correlated inversely with HOMA-IR in SLE patients.
      CONCLUSIONS: Elevated levels of adiponectin in SLE, despite inverse correlation
      with IR, suggest the possible involvement of adiponectin in IR and alterations in
      its effect on insulin sensitivity.

PMID- 16881112
TI  - Anti-NR2 glutamate receptor antibodies and cognitive function in systemic lupus
      erythematosus.
AB  - OBJECTIVE: To determine the prevalence of circulating anti-NR2 antibodies and
      their association with neuropsychiatric systemic lupus erythematosus (NP-SLE),
      particularly cognitive function, in women with SLE. METHODS: Cognitive function
      was assessed in 65 consecutive women with SLE from a single referral center using
      standardized neuropsychological tests. These were selected subtests of the
      Wechsler Adult Intelligence Scale-Revised, the Wechsler Memory Scale-Revised, and
      the California Verbal Learning Test, which provided information on 8 areas of
      cognitive function. After a mean followup of 64 (range 52-71) months, cognitive
      assessments were repeated. Global and domain-specific cognitive impairment was
      examined using predetermined decision rules, and the change in individual tests
      of cognitive performance over time was also examined. Overt NP-SLE was identified
      by clinical assessment and classified using the American College of Rheumatology
      nomenclature. Circulating IgG anti-NR2 and anti-dsDNA antibodies were determined
      by ELISA on up to 4 occasions over the study period. A positive result was
      defined as at least 3 standard deviations above the mean of healthy controls.
      RESULTS: At enrollment, 15/65 (23%) patients had cognitive impairment. This fell
      to 7/54 (13%) at followup. In addition 15/65 (23%) patients had a history of
      clinically overt NP-SLE. Twenty-three of 65 (35%) patients had anti-NR2
      antibodies and 48/65 (74%) had anti-dsDNA antibodies. Anti-NR2 antibodies were
      present in 18/48 (38%) patients with anti-DNA antibodies, and 18/23 patients
      (78%) with anti-NR2 antibodies also had anti-dsDNA antibodies. There was no
      association between global cognitive impairment, domain-specific cognitive
      impairment, or a history of clinically overt NP-SLE and either the presence or
      amount of anti-NR2 or anti-dsDNA antibodies (p > 0.05). When change in cognitive
      performance or the occurrence of new NP-SLE events over the 5-year followup
      period was examined, there was no significant association with persistent
      elevation of either antibody (p > 0.05). Similarly there was no association
      between a rise in autoantibodies over time and the development of overt NP events
      or cognitive decline (p > 0.05). CONCLUSION: These results indicate that anti-NR2
      antibodies occur in 35% of women with SLE and are infrequent in the absence of
      detectable anti-dsDNA antibodies. Their presence in the circulation is not
      associated with cognitive dysfunction at a single timepoint, and an increase in
      or persistently elevated antibody levels are not associated with a change in
      cognitive performance over time. There was no association with clinically overt
      NP-SLE. However, as our study did not examine cerebrospinal fluid samples, these
      results do not exclude a potential pathogenic role in selected patients for this
      group of autoantibodies should they penetrate the blood-brain barrier and thereby
      gain direct access to neuronal tissues.

PMID- 16881113
TI  - Prognostic factors in lupus nephritis: diagnostic and therapeutic delay increases
      the risk of terminal renal failure.
AB  - OBJECTIVE: To evaluate the prognostic significance of clinical and renal biopsy
      findings in an unselected cohort of patients with systemic lupus erythematosus
      (SLE) and nephritis. METHODS: Ninety-one patients with lupus nephritis were
      included in the study. Renal biopsies were classified according to the WHO
      criteria and examined for the presence of active and chronic histological
      changes. Predictors of endstage renal disease (ESRD) were identified by
      univariate and multivariate analyses. RESULTS: The median followup time was 6.1
      years (0.1-30.0 yrs). In all cases, immunosuppressive treatment was initiated or
      intensified within one month following renal biopsy. The cumulative incidence of
      ESRD after 1, 5, and 10 years was 3.5%, 15%, and 17%, respectively. A variety of
      clinical and biopsy findings including several histological markers of chronic
      renal damage were identified as univariate predictors of ESRD. In multivariate
      regression analyses, duration of nephritis symptoms > 6 months prior to biopsy, s
      creatinine > 140 micromol/l, diffuse proliferative glomerulonephritis, and
      tubular atrophy emerged as the strongest combination of independent risk factors
      (relative hazard ratios: 9.3, 5.6, 8.9, and 3.1, respectively). CONCLUSION: Our
      results confirm the negative prognostic impact of hypercreatininemia, class IV
      histopathology, and tubular atrophy in lupus nephritis. Our data show that delay
      between onset of nephritis and renal biopsy constitutes an important risk factor
      of ESRD. Patients with SLE should have kidney biopsy as soon as clinical signs of
      nephritis are evident in order to accelerate treatment decisions and minimize
      risk of inflammation-induced irreversible kidney damage.

PMID- 16881114
TI  - Inter-hospital transfers of patients with systemic lupus erythematosus:
      characteristics, predictors, and outcomes.
AB  - OBJECTIVE: To describe the reasons for inter-hospital transfers of patients with
      systemic lupus erythematosus (SLE), to identify predictors of transfers, and to
      compare the risk of in-hospital mortality between patients who were transferred
      and those not transferred. METHODS: Data on acute care hospitalizations of
      patients with SLE in New York and Pennsylvania in 2000-2002 were obtained from
      state health planning agencies. We identified inter-hospital transfers from
      discharge and admission codes, and categorized the major reason for transfer
      (rehabilitation, procedure, or continued medical care). Patient and hospital
      characteristics were examined as predictors of transfers. We used a matched
      cohort design with propensity adjustment to compare in-hospital mortality between
      patients transferred for continued medical care and those who were not
      transferred. RESULTS: We identified 533 inter-hospital transfers in 490 patients,
      524 of which involved one transfer per hospitalization episode. Of these 524
      transfers, 122 (23.3%) were for rehabilitation, 158 (30.1%) were for procedures,
      and 244 (46.6%) were for continued medical care. Patient characteristics and
      transfer destinations varied among these groups. Transfers for continued medical
      care were more common among younger patients, those who were more severely ill,
      had an emergency or urgent admission, or were hospitalized in a smaller, rural or
      non-teaching hospital, or in Pennsylvania, and were less common among those at
      proprietary hospitals. In the matched cohort analysis, the risk of in-hospital
      mortality was 2.25 times higher (95% confidence interval 1.31, 3.85; p = 0.004)
      among those transferred compared with those who were not transferred. This risk
      differed with the experience of the attending physician at the receiving
      hospital: among patients of physicians who treated 3 or fewer patients with SLE
      per year, this risk was 2.5 times higher (95% CI 1.42, 4.36; p = 0.002), while
      among patients of physicians who treated more than 3 patients with SLE per year,
      this risk was 0.56 times (95% CI 0.06, 5.12; p = 0.62) that of matched controls.
      CONCLUSION: Patient and transferring hospital characteristics vary with the
      reason for transfer. Transfers for continued medical care are associated with
      higher risks of in-hospital mortality, but these risks may differ with the SLE
      related experience of the attending physician at the receiving hospital.

PMID- 16881115
TI  - The efficacy of self-administered stretching for finger joint motion in Japanese
      patients with systemic sclerosis.
AB  - OBJECTIVE: To determine the efficacy of self-administered stretching of each
      finger in Japanese patients with systemic sclerosis (SSc). METHODS: Forty-five
      patients with SSc (32 with diffuse cutaneous SSc and 13 with limited cutaneous
      SSc) were given instructions on self-administered stretching and were directed to
      perform it every day. Individual fingers were maintained in a stretched position
      using the opposite hand for 10 seconds and this was repeated 3-10 times. To
      evaluate the effect of the stretching program, finger passive range of motion
      (ROM) was assessed using a goniometer on the first visit and after 1 month and 1
      year of the stretching program. The Health Assessment Questionnaire (HAQ) was
      also assessed on the first visit and 1 year afterward. RESULTS: The total passive
      ROM was significantly improved in each finger after 1 month of finger stretching.
      The total passive ROM was further improved or maintained within 1 year after the
      first visit. Although ROM was less in patients with diffuse cutaneous SSc than in
      those with limited cutaneous SSc at the first visit, ROM increased significantly
      irrespective of disease duration or severity of skin sclerosis. Finger stretching
      may improve the finger function, since the HAQ score for hand functions such as
      eating and gripping was significantly decreased. CONCLUSION: Our original self
      administered stretching program may be useful for improving finger joint motion
      in patients with SSc; future studies in various ethnic populations will be needed
      to determine the universal efficacy of this method.

PMID- 16881116
TI  - Characterization and differentiation of autoimmune versus viral liver involvement
      in patients with Sjogren's syndrome.
AB  - OBJECTIVE: To analyze the prevalence and clinical significance of liver
      involvement in patients with Sjogren's syndrome (SS), focusing on the
      characterization and differentiation of autoimmune versus chronic viral liver
      disease. METHODS: We investigated liver involvement (clinical signs, analytical
      data, chronic viral infections, and autoantibodies) in 475 consecutive patients
      with SS. All patients fulfilled 4 or more of the 1993 European Community Study
      Group criteria for SS. RESULTS: Liver involvement was detected in 129 (27%)
      patients. After ruling out chronic illnesses or use of hepatotoxic drugs, the
      main etiologies were chronic viral liver disease in 64 (13%) cases [chronic
      hepatitis C virus (HCV) infection in 63 and HBV infection in one] and autoimmune
      liver diseases in 24 (5%; primary biliary cirrhosis in 16 patients and type-1
      autoimmune hepatitis in 8). The analytical liver profile was not useful in
      differentiating between viral and autoimmune liver disease. In contrast, patients
      with SS and autoimmune liver disease presented higher mean values of erythrocyte
      sedimentation rate (p = 0.044), circulating gammaglobulins (p = 0.007), and a
      higher prevalence of antinuclear antibodies (p < 0.001), antimitochondrial
      antibodies (p < 0.001), anti-smooth muscle antibodies (p = 0.026), anti-Ro/SSA (p
      < 0.001), and anti-La/SSB (p = 0.01), while patients with chronic viral liver
      disease had a higher frequency of cryoglobulinemia (p < 0.001) and
      hypocomplementemia (p < 0.001). CONCLUSION: Chronic viral liver disease
      (associated overwhelmingly with HCV) was the main cause of liver involvement in
      our patients with SS, with a prevalence of 13%, nearly 3-fold greater than that
      observed for autoimmune liver involvement. The immunological pattern played a key
      role in the differentiation of viral (predominance of cryoglobulins and low
      complement levels) and autoimmune (higher frequency of autoantibodies) liver
      involvement.

PMID- 16881117
TI  - Platelet-endothelial cell adhesion molecule-1 and CD146: soluble levels and in
      situ expression of cellular adhesion molecules implicated in the cohesion of
      endothelial cells in idiopathic inflammatory myopathies.
AB  - OBJECTIVE: Idiopathic inflammatory myopathies (IIM) are a heterogeneous group of
      diseases characterized by chronic inflammation of muscles. We investigated the
      role of cellular adhesion molecules implicated in the cohesion of endothelial
      cells in IIM. METHODS: In 22 patients with IIM we investigated plasma
      concentrations of soluble junctional adhesion molecules [platelet-endothelial
      cell adhesion molecule (sPECAM-1) and sCD146] and cellular adhesion molecules [sP
      selectin, sE-selectin, intercellular adhesion molecule (sICAM-1), and vascular
      cell adhesion molecule (sVCAM-1)] implicated in leukocyte/endothelial cell
      interactions. Results were compared to a control group. Muscle biopsy samples
      from 8 out of 22 IIM patients were studied by immunohistochemistry for tissue
      expression of these molecules and compared to normal muscle samples. PECAM-1 and
      CD146 expression was also studied using immunoblots from muscle biopsies from 5
      patients and 2 controls. RESULTS: We observed distinct patterns of soluble levels
      and in situ expression between dermatomyositis (DM), polymyositis (PM), and
      sporadic inclusion body myositis (s-IBM). PM samples showed significantly
      increased levels of sCD146, sPECAM-1, and s-ICAM1 and increased expression of
      CD146, CD31, and ICAM-1 in endothelial cells, whereas CD146 and ICAM-1 were also
      recorded in some muscle fibers. In DM, sE-selectin, sP-selectin, and sPECAM-1
      were significantly increased, with abnormal expression of ICAM-1 in endothelial
      cells and perifascicular muscle fibers. In the small group of s-IBM samples,
      results were similar to PM, but the only significant increase was the level of
      sPECAM-1. Immunoblots confirmed increased expression of PECAM-1 and CD146 in all
      IIM muscles in comparison to controls, with the highest expression in PM and IBM
      samples. CONCLUSION: We observed abnormal increases of soluble levels of adhesion
      molecules implicated in endothelial cell junctions in PM (sCD146, sPECAM-1) and
      to a lesser extent in DM and s-IBM (sPECAM-1). We conclude that the distinctly
      different profiles between PM/s-IBM and DM reflect differences in the
      pathophysiological background of these diseases.

PMID- 16881118
TI  - Etanercept in adult patients with early onset ankylosing spondylitis.
AB  - OBJECTIVE: To determine whether twice-weekly subcutaneous etanercept improves the
      signs and symptoms of adult patients with early onset ankylosing spondylitis
      (AS). METHODS: A retrospective analysis was performed on a subgroup of patients
      with AS with onset < 18 years of age from a multicenter, double-blind, placebo
      controlled, randomized study of etanercept in the treatment of patients with AS.
      Twenty patients met criteria and are presented. RESULTS: As early as week four,
      5/9 (56%) patients who received etanercept achieved an Assessments in Ankylosing
      Spondylitis 20% response (ASAS 20) versus only 1/11 (9%) of those who received
      placebo (p = 0.032). The observed ASAS 20 response continued through week 24,
      with 6/9 (66%) patients receiving etanercept responding, versus 2/11 of patients
      receiving placebo (p = 0.025). CONCLUSION: Etanercept improves signs and symptoms
      of early onset AS in adult patients for at least 24 weeks.

PMID- 16881119
TI  - Femoral bone mineral density is associated with vertebral fractures in patients
      with ankylosing spondylitis: a cross-sectional study.
AB  - OBJECTIVE: To determine the association between vertebral fractures and clinical,
      laboratory, and radiological variables in patients with ankylosing spondylitis
      (AS). METHODS: Sixty-eight men with AS and 91 sex- and age-matched controls were
      consecutively enrolled. Vertebral fractures were assessed according to a visual
      semiquantitative grading system using plain radiographs of the lumbar spine
      obtained from patients with AS. Disease activity variables including C-reactive
      protein, erythrocyte sedimentation rate, finger-to-ground distance score,
      Schober's Index score, Bath Ankylosing Spondylitis Radiology Index for the spine
      (BASRI-s) score, and syndesmophyte score were identified. Assessments of bone
      mineral density (BMD) of the lumbar spine and the femur in patients and controls
      were performed using an anteroposterior dual energy x-ray absorptiometry
      technique. RESULTS: Eleven patients (16.2%) out of the total of 68 patients with
      AS had vertebral fractures; these were identified as wedge deformities (n = 5) or
      biconcave (n = 6) deformities. BMD levels of the lumbar spine and femur in
      patients were significantly reduced compared with those of age-matched controls.
      There were significant differences in the Schober's Index scores, finger-to
      ground distance scores, BASRI scores of the lumbar spine, syndesmophyte scores,
      and intertrochanter values of BMD among AS patients both with and without
      vertebral fractures. Multiple logistic regression analyses revealed that
      intertrochanteric BMD values also were independently associated with vertebral
      fractures in AS (p = 0.041). CONCLUSION: We demonstrated evidence of a
      correlation between low femoral BMD levels and risk of vertebral fractures in
      patients with AS, especially at the intertrochanteric area. Longitudinal studies
      in a large population are required to determine the diagnostic implications of
      femur BMD for increased risk of vertebral fractures in AS.

PMID- 16881120
TI  - Osteopenia is common in adult male patients with active juvenile idiopathic
      arthritis.
AB  - OBJECTIVE: To assess the prevalence of osteopenia in Southeast Asian men with
      active juvenile idiopathic arthritis (JIA) and to identify predictors of reduced
      bone mineral density (BMD). METHODS: BMD of 30 men with active JIA and 23 healthy
      men was assessed by dual energy x-ray absorptiometry scans. Clinical variables
      that influence bone mass were also analyzed. T scores were calculated based on
      Caucasian normative data. RESULTS: Absolute BMD (g/cm(2)) was significantly lower
      in men with active JIA compared to controls at all measured sites, i.e., lumbar
      spine (p = 0.018), hip (p = 0.018), and distal third of forearm (p = 0.044). More
      subjects in the JIA group had low BMD (T score <or= -1.0) than controls at hip
      (22/30 vs 9/23; p < 0.05) and distal third of forearm (27/30 vs 10/23; p <
      0.001), while at lumbar spine region the difference was not statistically
      significant (22/30 vs 13/23). A significant negative correlation of BMD was found
      with joint deformities, limitation of joint movement, Health Assessment
      Questionnaire score, and erythrocyte sedimentation rate. BMD at the hip and
      distal third of forearm was significantly lower in patients having arthritis at
      these sites. A positive correlation of BMD was found with body mass index.
      CONCLUSION: A majority of Southeast Asian men with active JIA have reduced BMD.
      More patients in our cohort had low BMD compared to reports from Western
      countries. This finding may be attributed to use of Caucasian normative data,
      uncontrolled disease activity, severity of disease, poor nutritional status, or
      an ethnic variation.

PMID- 16881121
TI  - Determinants of change in patella cartilage volume in healthy subjects.
AB  - OBJECTIVE: To examine whether the amount of patella cartilage in healthy, middle
      aged subjects is stable or changes over time, and what factors may influence the
      changes. METHODS: Eighty-five subjects (28 men and 57 women, mean age 55.5 yrs)
      had magnetic resonance imaging of their dominant knee at baseline and 2 years
      later. Patella and tibial cartilage volume was measured at baseline and followup.
      Risk factors assessed at baseline were tested for their association with change
      in patella cartilage volume over time. RESULTS: Mean annual percentage loss of
      patella cartilage was 2.1 (95% confidence interval: 1.1-3.2; p < 0.001). Age,
      gender, body mass index, and initial cartilage volume did not affect rate of
      change of patellar cartilage volume. There was a weak association between change
      in patellar cartilage volume and change in lateral tibial cartilage volume (R =
      0.23, p = 0.03) but not medial tibial cartilage volume (R = 0.09, p = 0.43).
      CONCLUSION: In healthy subjects, a significant amount of patella cartilage is
      lost annually. The poor correlation between patella and tibial cartilage loss
      suggests that pathogenetic mechanisms for osteoarthritis in the patellofemoral
      and tibiofemoral joint may differ. Further work will be required to determine
      whether the rate of patella cartilage loss in healthy subjects is steady or
      phasic, and to determine which factors can be modified to reduce cartilage loss.

PMID- 16881122
TI  - Nitrite and nitrotyrosine concentrations in articular cartilage, subchondral
      bone, and trabecular bone of normal juvenile, normal adult, and osteoarthritic
      adult equine metacarpophalangeal joints.
AB  - OBJECTIVE: Osteoarthritis (OA) is a chronic debilitating joint disorder in which
      the importance of inflammation is increasingly recognized. In advanced cases,
      both the articular cartilage and the underlying bony layers are affected, but the
      exact sequence of events and their localization in the initial phase of
      pathogenesis remain uncertain. We measured nitric oxide (NO) end products in
      tissue layers that constitute the bearing surface of the joint, as possible
      indicators of physiological and pathological processes. METHODS: Nitrite as a
      measure for NO and nitrotyrosine was measured in articular cartilage, subchondral
      bone, and the underlying trabecular bone of the proximal articular surface of the
      first phalanx of healthy mature horses (n = 15; age range 5-18 yrs), mature
      horses affected by OA (n = 15; age range 8-22 yrs), and unaffected juvenile
      horses (n = 13; age range 6 months-4 yrs). Data were correlated with cartilage
      damage, as quantified by the Cartilage Degeneration Index. RESULTS: In all 3
      layers the nitrite concentration was higher in OA joints (cartilage, p < 0.001;
      subchondral and trabecular bone, p < 0.05). The concentration of nitrite was
      significantly higher in cartilage and subchondral bone of juvenile horses
      compared with mature horses (p < 0.001). Nitrotyrosine concentrations were
      significantly higher in subchondral bone of OA horses compared with healthy
      controls (p < 0.001), but significantly lower in trabecular bone of juvenile
      horses (p < 0.01). CONCLUSION: The similarities observed over the 3 tissue layers
      support the concept of the bearing surface of the joint as a functional entity.
      Nitrite concentration seems to be a good indicator of tissue metabolic activity,
      but cannot discriminate between physiological (juvenile animals) and pathological
      (OA cases) processes. The increased nitrotyrosine levels in subchondral bone of
      OA-affected animals suggest that this layer is important in early or moderate OA,
      and implies a role of oxidative stress in the development of the disease.

PMID- 16881123
TI  - Possession of assistive devices is related to improved psychological well-being
      in patients with rheumatic conditions.
AB  - OBJECTIVE: To investigate the relationship between the possession of assistive
      devices and psychological well-being in patients with rheumatic conditions.
      METHODS: Patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA)
      were selected from rheumatology outpatient clinics in 2 adjacent regions in The
      Netherlands and Germany. A total of 142 patients completed a questionnaire on the
      possession of assistive devices and psychological well-being. Questions on
      sociodemographics, clinical status, and health status were included. Hierarchical
      multiple linear regression analysis was used to determine the unique association
      between the number of assistive devices per patient and psychological well-being,
      controlling for confounding variables. RESULTS: Univariately, the number of
      assistive devices per patient was negatively associated with psychological well
      being. Multivariately, the number of assistive devices per patient was positively
      associated with psychological well-being. Functional status was a negative
      confounder of the relationship between the possession of assistive devices and
      psychological well-being. CONCLUSIONl The possession of assistive devices was
      positively related to psychological well-being of patients with rheumatic
      diseases, after controlling for differences in functional status.

PMID- 16881124
TI  - Inhibited apoptosis of synovial fluid lymphocytes in children with juvenile
      idiopathic arthritis is associated with increased expression of myeloid cell
      leukemia 1 and XIAP proteins.
AB  - OBJECTIVE: Inhibited apoptosis of lymphocytes present in synovial fluid (SFL) and
      persistently infiltrating synovial tissue may be crucial in the pathogenesis of
      rheumatoid arthritis (RA). Similarly, this may be the case in juvenile idiopathic
      arthritis (JIA). Little is known about lymphocyte apoptosis in this disease.
      Recently, we reported significantly enhanced apoptosis of peripheral blood
      lymphocytes (JIA-PBL) compared to synovial fluid (JIA-SFL) or healthy
      lymphocytes, with downregulation of p53 in JIA-SFL. In this study we assessed
      other possible molecular mechanisms of this phenomenon. METHODS: PBL from 31
      children with JIA and 26 healthy children were examined. SFL obtained from 18
      patients was also studied. Apoptosis was assessed by TdT-mediated dUTP-biotin
      nick-end labeling (TUNEL) method. Expression of several apoptosis-regulating
      proteins was analyzed, including myeloid cell leukemia 1 (Mcl-1), cross-linked
      inhibitor of apoptosis (XIAP), FLICE-inhibitory protein (FLIP), or Bcl-xL
      inhibitors and proapoptotic p53, Bcl-w, Bak, and Bid. RESULTS: We found
      significant overexpression of Mcl-1 and XIAP in JIA-SFL (p < 0.001 and p < 0.02,
      respectively). Expression of Mcl-1 and XIAP in SFL correlated inversely with the
      apoptotic index (p < 0.002 and p < 0.01, respectively). FLIP expression was also
      distinctly higher in SFL than in JIA-PBL; however, the difference was not
      statistically significant (p = 0.061). No statistically significant differences
      were found in the expression of other proteins between SFL and PBL. CONCLUSIONS:
      This is the first study showing that upregulation of anti-apoptotic Mcl-1 and
      XIAP proteins, along with downregulation of p53 protein, is correlated with
      inhibition of JIA-SFL apoptosis.

PMID- 16881125
TI  - Efficacy of probenecid for a patient with juvenile dermatomyositis complicated
      with calcinosis.
AB  - Calcinosis of juvenile dermatomyositis (JDM) is a crucial problem because it is
      refractory to various therapies. An 11-year-old boy who had been treated for JDM
      with interstitial pneumonia developed calcinosis of both legs despite treatment
      with corticosteroid and cyclosporin A. Images of his knees showed massive
      calcinosis with restricted range of motion. Probenecid was used to reduce
      calcinosis, resulting in remarkable improvement of calcinosis accompanied by
      normalization of serum phosphorus level and disability after 17 months of
      administration. We suggest that probenecid is useful for the treatment of
      calcinosis of JDM.

PMID- 16881126
TI  - Ischemic scleroderma wounds successfully treated with hyperbaric oxygen therapy.
AB  - Hyperbaric oxygen therapy (HBOT) has been used to treat refractory wounds for the
      last several decades, with the majority of research focusing on wounds secondary
      to arterial insufficiency. We describe 2 patients with scleroderma with
      intractable bilateral extremity ulcers. Local ischemia was identified using
      transcutaneous oximetry. Each patient then underwent 30 treatments of HBOT at a
      relative depth of 2.4 ATA with resulting wound healing. This is the first
      reported successful use of HBOT to treat scleroderma ulcers, and may represent an
      unrecognized treatment option for these notoriously difficult chronic wounds.

PMID- 16881127
TI  - Cutaneous mastocytosis in a patient with primary Sjogren's syndrome.
AB  - Mast cells have been linked to rheumatoid arthritis (RA) and are essential to the
      pathogenesis of RA-like disease in a mouse model. We describe a 34-year-old woman
      who developed Sjogren's syndrome concurrently with telangiectasia macularis
      eruptiva perstans (TMEP), a rare form of cutaneous mastocytosis. The patient had
      sicca symptoms with an abnormal minor salivary gland biopsy and decreased
      salivary flow, peripheral neuropathy, an 80 pound weight loss, and a macular
      erythematous rash that exhibited superficial perivascular mast cell infiltrates
      on biopsy of lesional skin. This case further underscores the link between mast
      cells and the development of autoimmunity.

PMID- 16881128
TI  - Rapid destruction of the femoral head after a single intraarticular injection of
      corticosteroid into the hip joint.
AB  - We describe a 50-year-old woman who had a 10-year history of left groin pain. She
      experienced rapid collapse of the femoral head during a 3-month period after a
      single injection of corticosteroid into the hip joint, in which osteonecrosis was
      histologically observed.

PMID- 16881129
TI  - Marked pneumatosis cystoides intestinalis in a patient with mixed connective
      tissue disease.

PMID- 16881130
TI  - Concomitant polyarticular septic and gouty arthritis.

PMID- 16881131
TI  - Leukemic infiltration of the knee.

PMID- 16881132
TI  - Is the Jadad score the proper evaluation of trials?

PMID- 16881134
TI  - Prevalence of rheumatoid arthritis.

PMID- 16881136
TI  - Antibodies against alpha-fodrin are associated with dry eyes and mouth in the
      general population.

PMID- 16881137
TI  - WHO-ILAR COPCORD pilot study in Tehran, Iran.

PMID- 16881138
TI  - Certain hope.

PMID- 16881139
TI  - A role for proteinase-activated receptor-1 in inflammatory bowel diseases.

PMID- 16881140
TI  - Gaza crisis continues to worsen as all eyes turn to Lebanon.

PMID- 16881141
TI  - Belgian loophole allows Swiss parents a "saviour" baby.

PMID- 16881142
TI  - Protein nitration increased by simulated weightlessness and decreased by
      melatonin and quercetin in PC12 cells.
AB  - A variety of experiments suggest that space flight is associated with an increase
      in oxidative stress in organism. To explore the effects of oxidative stress on
      neuronal cells during microgravity, we used rat pheochromocytoma (PC12) cells as
      a neuronal cell model, cultured in a clinostat, which could simulate
      microgravity, to investigate the effects of reactive nitrogen species on protein
      nitration in PC12 cells during clinorotation. The effects of melatonin and
      quercetin on protein nitration in PC12 cells were also assayed to evaluate the
      possible protective role of melatonin or quercetin as an antioxidant. The results
      of immunological staining showed that after the 3 days' clinorotation the protein
      expressions of neuronal nitric oxide synthase and inducible nitric oxide
      synthesis were up-regulated. Our data also reflected that the concentrations of
      nitric oxide and nitrotyrosine were significantly increased after clinorotation,
      and they were reduced markedly in cells that were treated with 50 micromol/L
      melatonin or 0.5 micromol/L quercetin during simulated microgravity, when
      compared to those of control cells. These results suggest that clinorotation
      induced weightlessness increases oxidative stress responses in PC12 cells, and
      melatonin or quercetin was shown to protect PC12 cells from oxidative damage
      during simulated weightlessness.

PMID- 16881145
TI  - Naevus sebaceous.

PMID- 16881146
TI  - Three-dimensional laser scanning of cultural heritage: the deer stones of
      Mongolia.

PMID- 16881148
TI  - Treat the tingling. How to handle nerve pain.

PMID- 16881149
TI  - Healthy eating. Need to cool off? Try a summer salad.

PMID- 16881150
TI  - From fat to fit. Arkansas Governor Mike Huckabee tells Diabetes Forecast what
      he's gained (and lost) by getting into shape.

PMID- 16881151
TI  - The next generation: continuous glucose monitors.
AB  - These "real-time" monitors promise to change the way we chart ups and downs, by
      delivering readings every few minutes around the clock. But don't toss your old
      monitors just yet!

PMID- 16881152
TI  - Kid tested, kid approved recipes. Think kids are interested only in junk food?
      Pioneering chef Alice Waters and her team at The Edible Schoolyard say think
      again.

PMID- 16881153
TI  - Diving with diabetes. What you should know before you dive in.

PMID- 16881154
TI  - Research profile. Saving you the trip. Health care by phone. Raymond O. Estacio,
      MD.

PMID- 16881156
TI  - Automation of sentinel event reporting.

PMID- 16881155
TI  - Cancer risk among nuclear workers.

PMID- 16881157
TI  - Interpreting research studies.

PMID- 16881158
TI  - The electronic Statement of Conditions.

PMID- 16881159
TI  - The William Nelson ECG quiz.

PMID- 16881160
TI  - [An Italian pediatrician in India. Interview by Gaia de Bouvigny].

PMID- 16881161
TI  - Ethical and social dilemmas in community-based controlled trials in situations of
      poverty: a view from a South African project.
AB  - All psychological and social research presents ethical dilemmas, many of which
      centre around the difficulties which flow from the power imbalances between those
      conducting the research and the research respondents or participants. Issues of
      power are magnified in research undertaken in contexts of poverty, and there is a
      burgeoning literature on ethical issues in research in developing countries. In
      this article, we augment the existing literature by focusing on the experiences
      of an assessor working in a controlled trial of a mother-infant intervention in a
      poor South African community. We consider issues of community expectations, the
      presentation to our project of physical health problems, the issue of HIV/AIDS,
      cultural beliefs which impact on the research, child protection issues, and the
      tensions between research assessment and ubuntu--a cultural norm which requires
      helpful engagement with others. We suggest that our experiences may assist with
      the development of further research.

PMID- 16881163
TI  - Bibliography. Current world literature. Esophagus.

PMID- 16881162
TI  - A chat on fat in liver.

PMID- 16881164
TI  - [Early administration of vitamin D and maintenance therapy of secondary
      hyperparathyroidism: discussion].

PMID- 16881165
TI  - Hospital peer review standards and due process: moving from tort doctrine toward
      contract principles based on clinical practice guidelines.

PMID- 16881166
TI  - [Surgical treatment of lung cancer complicated by intrathoracic inflammatory
      paracancrous alterations].
AB  - An experience with diagnostics and surgical treatment of 291 patients with
      complicated course of lung cancer is described with special reference to
      specificities of the clinical course, preoperative management and operation
      technique. It was shown that the purposeful preoperative management allowed the
      assessment of the patients, previously thought to be inoperable, to be revised in
      25% of cases, and the frequency of postoperative complications and lethality to
      be reduced to 14 and 3.5% respectively. The 5 year survival of lung cancer
      patients with paracancrous alterations was 20.7%.

PMID- 16881167
TI  - [Causes of nonradical surgical operations for cancer of the proximal part of the
      stomach].
AB  - An analysis of results of treatment of 454 patients operated for cancer of the
      proximal part of the stomach included the main parameters of the tumor process
      and radical operations studied on the basis of morphological investigations of
      the ablated preparations. The vertical and horizontal lines of the gastric
      resection were thoroughly investigated, the results being introduced in the
      protocol of the investigation. In 49 of 454 radically operated patients (10.7%)
      the line of resection passed through the zone of tumor infiltration. It was shown
      that the frequency of the tumor cells left along the resection line was
      substantially influenced not only by the growth character, the histological
      structure of the tumor and involvement of the esophagus, but also by the kind of
      operative access and surgery. We believe that in patients with poorly
      differentiated carcinomas (G3-G4) and endophylic-infiltrative forms of tumor
      growth it is necessary to principally widen the resection zones both in the
      vertical and lateral directions. It will allow avoidance of making the line of
      resection in the tumor infiltration zone. Not only the gastric resection zones
      but also all anatomical structures adjacent to the tumor ablated during the
      combined surgical operations should be thoroughly morphologically examined. The
      intraoperative urgent histological investigation of the gastric resection line
      must be made in all radical operations for gastric cancer.

PMID- 16881168
TI  - [Preventive surgical treatment of ulcer disease].
AB  - The state of gastric secretion in ulcer disease patients was investigated.
      Acidity was estimated by a computed analysis of 24 hour acidogastromonitoring
      with apparatus AG-24 MP "Gastroscan-24". The examination of 739 patients with
      chronic duodenal ulcers included 139 (18.8%) patients with exacerbation, 306
      (41.1%) with bleeding, 185 (25%) after suturing the perforation, 59 (8%) with
      stenosis + 50 healthy subjects. A correlation was found between the efficiency of
      antisecretory drugs and "malignancy" of the course of ulcer disease. An
      aggressive type of the course of ulcer disease was determined in 178 patients
      with indications for operation, but the operations were not performed, in 102 out
      of them long-term results were followed up. The long-term results of operative
      treatment of uncomplicated ulcer were followed up in 181 (59%) patients.

PMID- 16881169
TI  - [Measures of prevention of diffuse peritonitis after operations for colorectal
      cancer].
AB  - An experience with treatment of postoperative complications in patients with
      colorectal cancer in specialized and surgical hospitals and an analysis of
      results of treatment of patients with incompetent intestinal anastomoses
      depending on the surgical strategy have shown that reoperations for exclusion of
      the gut with the incompetent anastomosis with the first symptoms of a developing
      complication allows prevention of possible complication.

PMID- 16881170
TI  - [Operative treatment of Graves' disease: supersubtotal resection of the thyroid
      gland].
AB  - The article is devoted to an actual problem - decision on the volume of resection
      of the thyroid gland in patients with diffuse toxic goiter. On the basis of an
      analysis of long-tern results of surgical treatment of 604 patients preference is
      given to supersubtotal thyroidectomy with 2 g of the thyroid tissue left after
      surgery since it prevents the development of recurrent thyrotoxicosis as well as
      of a severe hypothyrosis even with a not regular taking levothyroxin. It was
      found that in children and adolescents the risk of the development of
      thyrotoxicosis is higher than in adults. The details of surgical operations
      responsible for preservation of the recurrent nerves and parathyroid glands are
      considered.

PMID- 16881171
TI  - [Lymphadenectomy in patients with thyroid cancer: 30 years experience in dealing
      with the problem].
AB  - The article presents an analysis of results of surgical treatment of 2092
      patients with cancer of the thyroid gland (CTG) using different kinds of
      lymphadenectomies. During 30 years 1076 different operations on the lymph nodes
      of the neck and mediastinum have been made by the same collective of surgeons.
      The improved strategy and technique of surgical treatment of patients with
      differentiated CTG, electrophysiological monitoring of the nerves resulted in
      less postoperative lethality (from 0.89% to 0%), less number of unilateral
      damages of the inferior laryngeal nerves (from 4.4% to 0.33%), bilateral pareses
      (from 2.1% to 0%), accessory nerves (from 2.7% to 0.1%). Surgical diagnostics of
      the regional metastases of cancer at the preclinical stage by means of
      intraoperative biopsy of not involved cervical lymph nodes of the 3-4 groups and
      the division of traumatic operations into 2 stages improved the immediate results
      and did not deteriorate the long-term results of treatment of CTG patients.

PMID- 16881172
TI  - [Diagnostic laparoscopy in gunshot wounds of the abdomen in children].
AB  - Diagnostic laparoscopy in gunshot wounds of the abdomen was performed in 14
      children. The diagnostic value of laparoscopic and other methods of diagnostics
      was evaluated. An analysis of the results has shown that laparoscopy for gunshot
      wounds of the abdomen in children is of great diagnostic value. The indications
      and contraindications for diagnostic laparoscopy in such cases have been
      formulated. The surgical strategy used reduced 3 times the number of unnecessary
      laparoscopies for gunshot wounds of the abdomen in children.

PMID- 16881173
TI  - [Method of surgical treatment of gastroesophageal reflux disease].
AB  - A new method of surgical treatment of sliding hiatal hernia is proposed to
      improve the results of treatment of patients with the gastroesophageal reflux
      disease. Successful treatment of 5 operations followed up for more than a year is
      described.

PMID- 16881174
TI  - [Application of a one-row everted suture in operations on the colon].
AB  - A method of a one-row everted intestinal suture for the formation of terminal
      terminal colon-colonic anastomosis was worked out in experiment in 32 dogs. The
      suture gives a good connection of fragments of the gut by wound surfaces by the
      type of sensory adaptation. High mechanical strength of the suture, absence of
      anastomosis stenosis, primary intension healing of the intestine wound were
      proved on the basis of using the method of pneumocompression, investigation of
      the stenosis index and histological investigation of the connection zone. The
      developed suture was used in 27 patients in forming anastomoses after operations
      on the colon. No complications resulting from the developed suture were noted.

PMID- 16881175
TI  - [Modern principles of diagnosis and surgical treatment of cancer of the
      esophagus].
AB  - On the basis of results of treatment of 430 patients with cancer of the esophagus
      a conclusion was made that radical surgery for this disease consisted in
      extirpation of the esophagus with a single stage gastroplasty with a gastric tube
      from the greater curvature. The abdominal-cervical access is thought to be
      justified when the tumor is located on the border between the middle and lower
      third, in the lower third of the thoracic part of the esophagus, in the abdominal
      part of the esophagus. In cases of marked dysphagia, distant metastases, profound
      invasion into the neighboring organs the endoscopic diathermal tunnelization of
      the tumor followed by placing of endoprosthesis is necessary.

PMID- 16881176
TI  - [Experience with using a carbonic implant for plasty of hernia defects].
AB  - Based on 3-year experiences with using "Karbonikus-P" as a transplant in 62
      patients the authors have found that a carbonic implant causes a marked reaction
      of tissues and sequestration of certain fibers. It is necessary to use the
      implant as a method of choice and to continue observations.

PMID- 16881177
TI  - [Complex diagnostics and surgical treatment of acute small bowel adhesive
      obstruction].
AB  - Results of the complex diagnosis and surgical treatment of 85 patients with acute
      commissural obstruction of the small bowel have shown that at the present-day
      stage of the early diagnosis of this disease the method of USI in combination
      with using metallic "contrast marks" (carried out in 14 patients) holds the
      leading place. U-shape anastomoses were preferred when making entero-enteral
      anastomoses and ileoascendoanastomoses which considerably decreased the frequency
      of incompetent sutures. The developed method of antegrade intubation of the
      digestive tract was used for correction of syndrome of enteral insufficiency in
      46 patients that resulted in a quicker restoration of the small bowel functioning
      (4-5 days) and correction of the enteral insufficiency syndrome (5-6 days).

PMID- 16881178
TI  - [The role of laparoscopy in diagnostics and treatment of acute surgical diseases
      and traumas of organs of the abdominal cavity].
AB  - Diagnostic laparoscopy was performed in 588 patients with acute surgical
      pathology and 165 patients with abdominal traumas as a diagnostic procedure in
      order to differentiate and define further strategy of treatment. Acute
      appendicitis was diagnosed in 207 patients, laparoscopic appendectomy being
      fulfilled in 72 of them. In 103 out of 165 patients with abdominal trauma
      injuries of internal organs were diagnosed, in the other 62 patients injuries
      were excluded. Acute pancreatitis was diagnosed in 40 patients, 28 of them
      underwent different laparoscopic procedures. Laparoscopy allowed the diagnosis of
      acute disturbances of mesenteric blood circulation in 16 patients.

PMID- 16881180
TI  - [Experience in treatment of locally disseminated and metastasizing tumors of
      organs of the small pelvis under conditions of surgical department of a city
      multifield hospital].
AB  - Combined, extended and cytoreductive operations for locally disseminated
      malignancies of the small pelvis organs have been widely used in the recent
      decade. The surgical method in this situation consists in a maximally possible
      ablation of all tumor foci, distant metastases included. Good equipment of the
      medical institution and proper qualification of the surgeons give low
      postoperative lethality and satisfactory long-term results.

PMID- 16881179
TI  - [Preventive plasty of the abdominal wall with endoprosthesis "Esfil" in
      operations on organs of the abdominal cavity].
AB  - An analysis of clinical and US investigations of the abdominal wall in 210
      patients with different surgical diseases of the abdominal cavity allowed
      division of the patients into three groups: without clinical and ultrasonic
      alterations, with a mild degree and with a severe degree of the anatomo
      functional weakness of the abdominal wall. Indications for preventive
      endoprosthesis of the abdominal wall were determined using the method of
      quantitative evaluation of risk factors of postoperative hernias developed by the
      authors. Preventive endoprosthesis of the abdominal wall with a polypropylene
      endoprosthesis "Esfil" was fulfilled during operation on organs of the abdominal
      cavity in 11.9% of the patients by absolute indications. The number of
      postoperative hernias was reduced to 0.9%.

PMID- 16881181
TI  - [Method of laser Doppler-flowmetry in the assessment of efficiency of
      sympathectomy in patients with upper extremity ischemia].
AB  - Changes to microcirculation were analyzed in 61 patients after 76 upper-chest
      sympathectomies. Rheovasography, transcutaneous determination of partial oxygen
      pressure in the tissues, laser Doppler-flowmetry were performed to evaluate the
      microcirculation. The data obtained give evidence of a significantly better
      microcirculation after the upper-chest sympathectomy.

PMID- 16881182
TI  - [Syndrome of diabetic foot and atherosclerosis of the lower extremity arteries].
AB  - Obstructive damages of the peripheral arteries in diabetes mellitus patients are
      known to occur 4 times more often than in patients not having diabetes. For the
      recent 10 years 390 patients with serious decompensated diabetes mellitus and
      diabetic foot have been examined and treated. The atherosclerotic process in the
      low extremity arteries in diabetes mellitus patients was found to be more
      distally located, symmetrical and the ischemia signs were quickly progressing and
      badly answered to treatment. As a rule, sympathectomy and restoring operations
      were ineffective, often followed by necrotic alterations of the foot skin and
      gangrene. Our data have shown that even young patients with the main type of
      blood flow having the diabetic foot syndrome have certain signs of
      atherosclerotic affection of the low extremity arteries. It must be taken into
      consideration in their treatment.

PMID- 16881183
TI  - [Hemangiopericytoma of the greater omentum].

PMID- 16881184
TI  - [Intercostal lung hernia resulting from a spontaneous rupture of the costal
      arch].

PMID- 16881185
TI  - [Giant schwannoma of the abdominal cavity].

PMID- 16881186
TI  - [A rare complication of the duodenal diverticulum].

PMID- 16881187
TI  - [Defects in conducting case histories in urgent abdominal surgery and their
      importance].
AB  - Information available in case histories is of great importance, e.g. for court
      examinations on "medical suits". So, we have investigated 472 case histories for
      the period from 2000 through 2004. It was found that the number of errors and
      short-comings in case histories still remains rather great. High professional and
      juridical competence is thought to be the way to avoid the patient's complains
      and improve effectiveness of treatment.

PMID- 16881188
TI  - [Local multilevel monitoring of resistance of pathogens of surgical infection].
AB  - Results of bacteriological investigations of patients with pyo-inflammatory
      surgical diseases and complications, environmental tests have been analyzed. The
      local multilevel monitoring of resistance was used as an instrument of permanent
      control of changes in the resistance of surgical infection pathogens to
      antibodies and for a decision on the schemes empiric antibacterial chemotherapy.

PMID- 16881189
TI  - [Syndrome of infectious-toxic shock in the structure of patients with necrotizing
      fasciitis].
AB  - Among 28 patients with necrotizing fasciitis 18 patients had the syndrome of
      infectious-toxic shock with clinically severe manifestations. Nine of them had
      the disease with most serious (lightening-like) clinical forms of severe sepsis
      that led to lethal outcomes within 1-3 days. This form is referred to as an
      irreversible septic shock and genetically is due to two factors: 1. Type of the
      pathogen (Streptococcus pyogenes) whose toxin is responsible for the septic shock
      syndrome. 2. Spacious zone of the superficial fascia necrosis, a massive source
      of endotoxemia resulting from generalized thrombosis of the microcirculation bed
      of the fascial structures. There is no alternative to the method of treatment of
      patients with necrotizing fasciitis but urgent (immediately after the diagnosis)
      and aggressive in volume and character operation as well as an adequate
      resuscitation management and antibiotic therapy.

PMID- 16881190
TI  - [Influence of the temperature regimen of sanitation of the abdominal cavity on
      the course of the syndrome of post-sanitation intoxication in patients with acute
      diffuse peritonitis].
AB  - The aim of the investigation was to work out and study effectiveness of the
      method of sanitation of the abdominal cavity in patients with acute diffuse
      peritonitis based on a combination of using the properties of hypo- and hyper
      thermal solutions. The complex of experimental investigations has proved the safe
      clinical use of the proposed method to be possible, discovered main pathogenetic
      mechanisms of a positive influence of heterothermy when performing sanitation of
      the abdominal cavity against the background of acute peritonitis. The results of
      clinical approbation of the method in 86 patients have shown sufficiently high
      efficiency of using sanitation of the abdominal cavity in heterothermal regimen
      in a complex of measures for treatment of patients with acute peritonitis that
      allowed getting reliably lower degree of post-sanitation intoxication, less
      number of complications and lethal outcomes.

PMID- 16881191
TI  - [Modern aspects of surgical endocrinology [XIII (XV) Russian Symposium on
      Surgical Endocrinology, City of Ryazan, September 14-16, 2005]].

PMID- 16881192
TI  - [Diagnostics and treatment of injuries to the duodenum].

PMID- 16881193
TI  - Update on symptomatic GERD.

PMID- 16881194
TI  - Endoscopic management of Barrett's esophagus.

PMID- 16881195
TI  - [Helicobacter pylori. Who to treat?].

PMID- 16881196
TI  - [Nonvariceal hemorrhage].

PMID- 16881197
TI  - [Anorexia nervosa and bulimia nervosa. Psychological considerations for its
      treatment].
AB  - It is presented the current perspectives in the study and treatment of the eating
      disorders, in specific: anorexia nervosa and bulimia nervosa, epidemiology, and
      the interface among the different medical specialties, nutrition and sciences of
      the behavior, the diagnostic approaches, instruments and current therapeutic
      models.

PMID- 16881198
TI  - [Gastrointestinal repercussions of obesity].

PMID- 16881199
TI  - [Endoscopic and surgical therapeutic options].

PMID- 16881200
TI  - [New concepts in the diagnosis and classification of the obese patient].

PMID- 16881201
TI  - [Capsule endoscopy: a great advance in the history of endoscopy].

PMID- 16881202
TI  - [Functional heartburn and esophageal reflux].

PMID- 16881203
TI  - [Functional dyspepsia].

PMID- 16881204
TI  - [What to do the the patient with irritable bowel refractory to conventional
      treatment].

PMID- 16881206
TI  - [Chronic diarrhea].

PMID- 16881205
TI  - Treatment of severe and intractable constipation.

PMID- 16881207
TI  - [Hemorrhage of obscure origin].

PMID- 16881209
TI  - [Diverticular colon disease. When to treat and when to operate].

PMID- 16881208
TI  - [Intestinal occlusion in cancer].
AB  - OBJECTIVE: To perform a review of the literature about the management of bowel
      obstruction in advanced cancer. BACKGROUND: Bowel obstruction is a common
      problem, mainly in patients with advanced colorectal or ovarian cancer. The
      management of this group of patients is complex and controversial. METHODS: A
      review of the English and Spanish literature about the clinical picture,
      diagnosis and management of bowel obstruction in advanced cancer was performed.
      RESULTS: Bowel obstruction is a common and distressing outcome in patients with
      abdominal or pelvic cancer. Patients may develop bowel obstruction at any time in
      their clinical history, with a prevalence ranking from 5.5 to 51% in those with
      ovarian cancer and from 10% to 28% in those with colorectal cancer. The causes of
      the obstruction may be benign postoperative adhesions, a focal malignant or
      benign deposit, or relapse or diffuse carcinomatosis. The symptoms, which are
      almost always present, are intestinal colic, continuous abdominal pain, nausea or
      vomiting. Although surgery should be the primary treatment for malignant
      obstruction, it is now recognized that some patients with advanced disease or in
      generally poor condition are unfit for surgery and require alternative management
      to relieve distressing symptoms. A number of treatment options are now available
      for the patient with advanced cancer who develops intestinal obstruction.
      CONCLUSIONS: Bowel obstruction in cancer patients is a common and difficult
      problem. Patients must be selected for surgery or palliative treatment of their
      symptoms based on their clinical status.

PMID- 16881210
TI  - [Biliary lithiasis. Strategies for management in subjects with nonspecific
      symptoms].

PMID- 16881211
TI  - [Exploration of biliary tracts for laparoscopy for treatment of
      choledocholithiasis].
AB  - BACKGROUND: Common bile duct stones are found in approximately 16% of patients
      undergoing laparoscopic cholecystectomy. If the diagnosis of choledocholithiasis
      is made in the preoperative work-up it is a common practice to refer patients to
      endoscopic retrograde cholangiography and endoscopic sphincterotomy. However, if
      the diagnosis is established during the intraoperative cholangiogram the surgeon
      confronts a therapeutic dilemma between laparoscopic common bile exploration,
      conversion to open surgery or post-operative endoscopic sphincterotomy.
      OBJECTIVE: We have opted to resolve the choledocholithiasis in only one session
      during the laparoscopic cholecystectomy, with the transcystic common bile duct
      exploration technique using the choledochoscope, or with laparoscopic
      choledochotomy. We report our early experience in terms of success of stone
      removal, operative time, morbidity, mortality and hospital stay. METHODS: from
      1992 to 2003 we performed 460 laparoscopic cholecystectomies and using selective
      cholangiography in 138 patients (30%) we found 52 patients with common bile duct
      stones, for an incidence of 11.3%. RESULTS: Of this group we performed
      laparoscopic common bile duct exploration in 46 patients, and our success rate
      for stone removal was 95.6% (44 of 46) with only two failures related to multiple
      stones and impactation at the ampulla for a conversion rate of 4%. The mean
      operative time was 120 +/- 40 min. A morbidity of 8.6% was found, with no
      mortality. Hospital stay was 48 hrs. Mean recovery time was 7 days, and time to
      return to work 15 +/- 3 days. CONCLUSIONS: We concluded that must of the patients
      with common bile duct stones found during laparoscopic cholecystectomy can be
      treated with success using the laparoscopic technique with choledochoscopy,
      without increased morbidity or mortality, and with a short hospital stay and
      recovery time similar to patients in whom only laparoscopic cholecystectomy is
      perform. According to our results we encourage that this method should become the
      primary strategy in the great majority of patients with common bile duct stones
      found during intraoperative cholangiography.

PMID- 16881212
TI  - [Endoscopic management of pseudocystic pancreas].

PMID- 16881213
TI  - [Surgical treatment of pancreatic pseudocyst].

PMID- 16881214
TI  - [Is antibiotic prophylaxis useful in acute pancreatitis?].

PMID- 16881215
TI  - [Endoscopic cholangiopancreatography vs. cholangiopancreatography magnetic
      resonance].

PMID- 16881216
TI  - [Biliary magnetic resonance].

PMID- 16881217
TI  - [Evaluation of the seriousness of acute pancreatitis].

PMID- 16881218
TI  - [Hepatitis C. How can we eradicate the definitive virus?].

PMID- 16881219
TI  - [Fatty liver and steatotic non-alcoholic hepatitis].

PMID- 16881220
TI  - [Liver fibrosis and cirrhosis: are they reversible?].

PMID- 16881221
TI  - Refractory ascites and hepatorenal syndrome.

PMID- 16881222
TI  - [Hepatic carcinoma: algorithm for therapeutic conduct].

PMID- 16881223
TI  - Update on liver transplantation.

PMID- 16881224
TI  - [A vision of future treatment of liver diseases].

PMID- 16881225
TI  - [Training of general practitioners in phthisiology].
AB  - The phthisiology teaching program for non-phthisiological physicians provides for
      the extension and strengthening of skills in diagnosis, differential diagnosis,
      intensive care, medical and surgical treatment, anesthesiology and resuscitation
      in patients with tuberculosis and in its prevention and early detection. The
      effective training of physicians is determined by the teacher's professional
      competence and the trainees' needs for the efficiency of an educational process.
      A great role in building up practical skills is played by the physicians'
      independent work that is an integral part of improvement of clinical thought and
      that is most significant in building up knowledge and skills. The efficiency of
      training envisages different forms of control: verbal, written, testing,
      practical, and combined, each being actively used while teaching phthisiology in
      non-phthisiological physicians.

PMID- 16881226
TI  - [Effect of surfactant-BL on ventilation and gas exchange function in patients
      with destructive pulmonary tuberculosis].
AB  - The fact that the treatment of pulmonary tuberculosis is a topical problem is
      beyond question. At present, it is well known that there is dissociation between
      the time of a negative sputum reaction and later cavernous healing, resolution of
      inflammatory changes. Therefore, search for new possibilities of pathogenetic
      action on the course of a tuberculous process, healing of destructive changes,
      and the maximum recovery of functional disorders are one of the ways of enhancing
      the efficiency of treatment in patients with destructive pulmonary tuberculosis.
      Over 70 years' history of the discovery and studies of the pulmonary surfactant
      system has made it possible to formulate a current concept of surfactant as a
      multicomponent system of cellular and non-cellular elements that ensure the
      antiatelectatic, antiedematous, protective, and other functions of the lung. The
      effects of surfactant preparations as an agent of pathogenetic therapy are being
      investigated at the Central Research Institute of Tuberculosis, Russian Academy
      of Medical Sciences. The present paper presents the results of changes in
      external respiratory function and gas exchange before and after surfactant
      therapy in 64 patients with established drug-resistant infiltrative pulmonary
      tuberculosis. Along with the performed antituberculous therapy, the natural agent
      Surfactant-BL made in Russia was used by taking into account individual
      sensitivity. The agent was inhalationally administered in a daily dose of 25 mg
      by the schedule for 8 weeks.

PMID- 16881227
TI  - [The cytokine profile in granulomatous lung diseases].
AB  - Twenty-five patients with new-onset pulmonary tuberculosis, 52 patients with
      active sarcoidosis, and 5 healthy donors were examined. Cytokines (IL-2, IL-4, IL
      6, TNF-alpha, and gamma-1FN were determined by enzyme immunoassay in the serum
      and cultured mononuclear supernatant from peripheral blood. IL-2, TNF-alpha, and
      gamma-IFN) were found in the sera of all the examinees. There were significant
      differences in the presence of IL-4 that was more commonly detected in
      sarcoidosis than in tuberculosis (96.2% versus 68%; p = 0.001) and in healthy
      individuals (40%; p = 0.0001) and in the presence of IL-6 (84.6% in patients with
      sarcoidosis; 20% in healthy individuals; p = 0.0015; 12% in patients with
      tuberculosis; p < 0.0001). Supernatant studies showed that IL-4 was absent in 25%
      of patients with sarcoidosis, nor gamma-IFN in 21.7% of patients with
      tuberculosis and in 12.5% of patients with sarcoidosis. In tuberculosis, the mean
      levels of IL-2, IL-4, IL-6, TNF-alpha, and gamma-IFN were greater than those in
      the control group; but these differences were not statistically significant
      primarily due to the fact that there was a great scatter of readings. In
      sarcoidosis, the serum levels of IL-4 (40.9 +/- 38.5 pg/ml) and IL-6 (19.0 +/-
      2.7 pg/ml) were significantly higher than those in healthy individuals (p = 0.01
      and p = 0.026, respectively) and in patients with tuberculosis (p = 0.0005 and p
      < 0.0001). The supernatant from patients with tuberculosis showed no significant
      differences in the content of cytokines than that from donors. In patients with
      sarcoidosis, the increase in the level of TNF-alpha (757.8 +/- 142.8 pg/ml) was
      statistically significant, as compared with the controls (p = 0.036) and patients
      with tuberculosis (p = 0.018), so as that of gamma-IFN (272.9 +/- 58.0 pg/ml), as
      compared with patients with tuberculosis (p = 0.046). Thus, the serum levels of
      IL-6 and IL-4 and the capacity of monocytes and macrophages for synthesizing TNF
      alpha and gamma-IFN may be used as an auxiliary criterion for the nosological
      diagnosis of sarcoidosis and tuberculosis.

PMID- 16881228
TI  - [Therapeutic plasmapheresis in patients with destructive pulmonary tuberculosis].
AB  - Therapeutic plasmapheresis was performed in 159 patients with pulmonary
      tuberculosis treated in the clinic in 2000 to 2005. Four hundred and seventy
      seven manipulations were made. Among its clinical forms, there was prevalent
      fibrocavernous tuberculosis (in 136 patients); 9 had infiltrative tuberculosis;
      caseous pneumonia was present in 5 patients; 4 had tuberculoma; 3 and 2 patients
      had focal and disseminated tuberculosis, respectively. Out of the 159 patients,
      42 (26.4%) underwent therapeutic plasmapheresis at the stages of surgical
      treatment. Plasmapheresis was made in 61.9% (26/42) before surgery and in 38.1%
      (n = 16). The study defined indications for and contraindications to therapeutic
      plasmapheresis in patients with destructive pulmonary tuberculosis, including
      adolescents and patients at the stages of surgical treatment. A procedure has
      been developed for discrete and membranous plasmapheresis for this category of
      patients. In patients with destructive patients, therapeutic plasmapheresis was
      shown: 1) to level the symptoms of antituberculous chemotherapy intolerance; 2)
      to correct homeostatic disorders; 3) to enhance the efficiency of basic drug
      therapy and to promote timely preparation of patients for surgery; 4) to improve
      the quality of life.

PMID- 16881229
TI  - [Infiltrative pulmonary tuberculosis under the conditions of a large industrial
      center of Siberia].
AB  - Among the patients with infiltrative pulmonary tuberculosis, there was a rise in
      the proportion of patients aged 40 years or older, the unemployed, and
      individuals with aggravating social risk factors in the study period (2000-2001
      and 1990). There was also an increase in the proportion of disseminated
      processes, cavity decay (2 cm or more in diameter), and massive bacterial
      isolation. The clinical manifestations of pulmonary tuberculosis were pronounced.
      Disseminated and destructive processes were more frequently detected among the
      patients having social risk factors, examined in the given period.

PMID- 16881230
TI  - [Clinical efficiency of course and long-term therapy with the angiotensin
      converting enzyme inhibitor perindopril in patients with chronic obstructive lung
      disease and cor pulmonale].
AB  - AIM: to evaluate the clinical efficiency of course and long-term therapy with the
      angiotensin-converting enzyme (ACE) inhibitor perindopril in patients with
      chronic obstructive lung disease (COLD) and chronic cor pulmonale (CCP).
      MATERIALS AND METHODS: Forty patients aged 40 to 56 years (mean 45.0 +/- 2.0
      years) who had COLD and CCP were examined. Hemodynamic parameters were recorded
      by M- and B-mode and Doppler echocardiographies. RESULTS: Addition of perindopil
      to course therapy in patients with COLD and CCP ameliorated pulmonary
      hypertension, positively affected central and peripheral hemodynanic parameters,
      and failed to have a negative impact on external respiratory function and renal
      and hepatic function. The long-term use of perindopril in individually adjusted
      doses in the outpatient setting showed pronounced beneficial clinical effects and
      considerably improved the morphofunctional parameters of the right cardiac
      cavities and patients' life quality. CONCLUSION: It is advisable to include the
      ACE inhibitor perindopril into complex therapy in patients with CCP in order to
      correct pulmonary and central hemodynamic disorders.

PMID- 16881231
TI  - [Electrocardiographic features in a significant commissural process in the upper
      lobe of the right lung].

PMID- 16881232
TI  - [Endoprosthesis of the hip joint in sequels of destructive forms of tuberculosis
      coxitis with cavitary and segmentary defects of the acetabulum].

PMID- 16881233
TI  - [Ultrasound evaluation of intrahepatic hemodynamic disorders in patients with
      renal tuberculosis].
AB  - Seroechography, duplex, color, and energy Doppler studies were used to examine 50
      patients with different forms of renal tuberculosis. The nature of renal blood
      flow was shown to depend on the magnitude of pathomorphological changes in
      tuberculous lesion. Spectral and energy Doppler studies revealed enhanced blood
      flow in the area of tuberculous infiltration. In all forms of nephrotuberculosis,
      there was an increase in peripheral vascular resistance, which was associated
      with vasoconstriction, obliteration, and diminished elasticity of vascular walls.
      Ultrasound angiography used in destructive forms of renal tuberculosis makes it
      possible to define treatment policy. The data of Doppler study were compared in
      relation to the glomerular filtration rate. The study ascertained that there was
      a reduction in glomerular filtration rates as the velocity characteristics of
      blood flow decreased and peripheral vascular resistance increased. The threshold
      values of renal hemodynamic parameters were determined to estimate renal
      filtration function. The reduction in end-diastolic blood flow velocity at
      different levels of the renal artery was of the greatest diagnostic informational
      value for diminished renal filtration function.

PMID- 16881234
TI  - [Effect of nephrophyte on the course of the hepatorenal syndrome caused by a
      complex of antituberculous drugs].
AB  - A complex of antituberculous drugs causes the hepatorenal syndrome in albino
      rats. The course administration of the plant agent nephrophyte in an experimental
      therapeutic dose during tuberculostatic therapy has a positive effect on the
      course of the hepatorenal syndrome.

PMID- 16881235
TI  - [Determination of multidrug resistance of M. tuberculosis by different methods].
AB  - Testing the direct nitrate reductase technique versus the absolute concentration
      test has indicated that the former may be successfully used for rapid
      determination of the sensitivity of Mycobacterium tuberculosis (MBT) to isoniazid
      and rifampicin and it can reduce the time of obtaining a result by 4-5 times in
      the cases that sputum bacterioscopy yielded a positive result that allows the
      modified method to be applied. The advantages of the TB-Biochip technique are the
      time of detection multidrug-resistant MBT (24 hours), a possibility of obtaining
      these data just when analyzing sputum-isolated MBT DNA, and characterization of
      the MBT genomic elements that are responsible for drug sensitivity to
      antituberculous agents, by determining mutations in the examined genes and this
      all by using one chip. The agreement of results of microbiological and molecular
      genetic studies study of drug MBT sensitivity was 98%. There were no differences
      in the results of those using isoniazid. As for rifampicin, there was a
      difference in two samples (3.8%). Analysis of a combination of mutations forming
      multidrug resistance indicated that 74.3% of multidrug-resistant MBT isolates had
      mutations in the codon Ser531 > Lue of the rpoB gene and in the codon Ser315 >
      Thr of the katG gene. 97.4% of strains with signs of multidrug resistance had
      mutations in the codon 315 of the katG gene. 20.5% of isoniazid-resistant strains
      were observed to have mutations in two genes (katG and inhA) and 28.2% of the
      strains exhibited double mutation in the katG gene - Ser315Thr and Ile335 > Val.

PMID- 16881236
TI  - [Public health care of Yakutia in 1920-1930: tuberculosis-control making].

PMID- 16881237
TI  - [Order no. 511 "On approval of health care standard for patients with cirrhotic
      pulmonary tuberculosis" issued by the Ministry of Health and Social Development
      on August 11, 2005].

PMID- 16881238
TI  - With recovery now in our public policy, is recovery in danger?

PMID- 16881239
TI  - Staff presence in job interviews is still suspect.

PMID- 16881240
TI  - What happened to civil rights?

PMID- 16881241
TI  - An ethnographic study of job seeking among people with severe mental illness.
AB  - An ethnographic study employing intensive participant observation methods
      identified critical differences in styles of searching for competitive employment
      among people with severe mental illness and explored the social/cultural
      correlates of these job-seeking styles. Propensity for active job seeking was
      strongly associated with younger age, with participants' involvement in
      interdependent kin networks or households, with ethno-racial minority background,
      and with capacity for coherent discourse. Active job seekers did particularly
      well in a supported employment program, but also were able to find employment
      when assigned to other programs; passive job seekers had little success in any
      vocational program. The authors discuss several implications of these findings
      for vocational services.

PMID- 16881242
TI  - Faculty perceptions of university students with psychiatric disabilities.
AB  - Information sources such as professional training, the media, personal
      relationships, and one's own experience may impact perceptions about people with
      psychiatric disabilities (PDs). The purpose of this study was to assess the
      relationship between information sources and university faculty members'
      perceptions of working with university students who have PDs. Specific types of
      personal experience were then analyzed: having a family member, friend, and
      student with a PD, and having a PD oneself. Faculty who had a friend or a student
      with a PD had more positive perceptions of university students with PDs than
      faculty who had neither of these experiences.

PMID- 16881243
TI  - The development of an observation tool for use with parents with psychiatric
      disability and their preschool children.
AB  - Community-based treatment and care of people with psychiatric disabilities has
      meant that they are now more likely to engage in the parenting role. This has led
      to the development of programs designed to enhance the parenting skills of people
      with psychiatric disabilities. Evaluation of these programs has been hampered by
      a paucity of evaluation tools. This study's aim was to develop and trial a tool
      that examined the parent-child interaction within a group setting, was functional
      and easy to use, required minimum training and equipment, and had acceptable
      levels of reliability and validity. The revised tool yielded a single scale with
      acceptable reliability. It had discriminative validity and concurrent validity
      with non-independent global ratings of parenting. Sensitivity to change was not
      investigated. The findings suggest that this method of evaluating parenting is
      likely to have both clinical and research utility and further investigation of
      the psychometric properties of the tool is warranted.

PMID- 16881245
TI  - Evaluating the effectiveness of a consumer-provided mental health recovery
      education presentation.
AB  - The current study investigated the effectiveness of the In Our Own Voice (IOOV)
      mental health education program in improving knowledge and attitudes about mental
      illnesses. Undergraduate participants (N = 114) completed three pre-test measures
      of knowledge and attitudes, attended either an In Our Own Voice presentation or a
      control presentation about psychology careers, and repeated the three measures
      following the presentation. Results indicated that the IOOV group showed
      significant positive change across time, as well as significantly greater
      improvement than a control group in their knowledge and attitude scores on all
      measures. These findings support the effectiveness of the IOOV program.

PMID- 16881244
TI  - Group treatment approaches to address cognitive deficits.
AB  - Psychiatric rehabilitation services are primarily delivered using group
      modalities. Recent evidence points to the deleterious effects of poor cognitive
      functioning on group involvement, skill development and functional outcomes. This
      paper reviews the impact of individual cognitive deficits on group functioning,
      discusses the rationale for using a cognitive framework for group development,
      and presents multiple examples of group programming with compensatory and
      remediation techniques to improve group functioning. Examples include modifying
      groups to address cognitive limitations, as well as developing groups targeting
      specific cognitive functions. The groups described are suitable for persons with
      serious and persistent mental illness across hospital and community treatment
      settings.

PMID- 16881246
TI  - Understanding help seeking delay in the prodrome to first episode psychosis: a
      secondary analysis of the perspectives of young people.
AB  - First episode psychosis represents a critical period for intervention to prevent
      future impairments and to initiate optimal interventions. Using an interpretive
      interactionist framework, a secondary analysis of interview transcripts was
      conducted based on the narratives of youth experiences of psychosis. Our goal was
      to better understand the factors involved in the decision to seek help (or not)
      from the mental health system. Findings suggest that help seeking is a social
      process involving a wide range of influences; two such influences are highlighted
      in this paper, an individual avoidant strategy of ignoring and hiding early
      symptoms, and the persuasive influence of significant others in the social
      network.

PMID- 16881248
TI  - Why I am not a "mental health consumer".
AB  - "Mental health consumer" is now a widely-accepted term used to identify
      individuals living with mental illness. Though this language may be an
      improvement over the word "patient," it can still be limiting and disempowering.
      The author explains her concern regarding the word "consumer" and explores the
      advantages of using the term "psychiatric disability" to describe the experience
      of those who live with mental illness.

PMID- 16881247
TI  - Comparing the CAAPE, a new assessment tool for co-occurring disorders, with the
      SCID.
AB  - Co-occurring mental health and substance use disorders (COD) are common and
      frequently under-detected, which may lead to less than optimal treatment for
      persons in psychosocial rehabilitation settings. A new, relatively brief
      instrument, the Comprehensive Addictions and Psychological Evaluation (CAAPE) was
      compared with the Structured Clinical Interview for DSM-IV (SCID). The CAAPE
      required less time to administer than the SCID, efficiently explored DSM
      substance use disorder criteria and served as a screen for psychiatric disorders.
      The CAAPE promises to be a useful screening and diagnostic instrument for persons
      with co-occurring disorders, especially suited for use in psychosocial
      rehabilitation.

PMID- 16881249
TI  - Training to increase cultural competence.

PMID- 16881250
TI  - The language faculty, Broca's region, and the mirror system.
AB  - Examples of three types of empirical arguments are given for the modularity of
      language mechanisms in Broca's region, and against a unified account of the
      functional role of this region and of the ventral precentral sulcus (vPCS). These
      are (a) pure syntactic considerations, (b) observations on the comprehension
      performance of Broca's aphasics, (c) recent fMRI results from receptive tasks at
      the sentence level.

PMID- 16881251
TI  - Why is Broca's area involved in syntax?
AB  - It is suggested that, rather than Broca's area playing its role in syntactic
      comprehension because its functions are a specialization those of the
      dorsolateral prefrontal cortex (DLPFC) or derived from sensori-motor functions of
      cortex from which it is evolutionarily descended, this region may be involved in
      this aspect of language because of its intrinsic neural organization.

PMID- 16881252
TI  - Broca's area and the ventral premotor cortex in language: functional
      differentiation and specificity.
AB  - The idea is put forward that Broca's area (BA 44/45) and the left ventral
      premotor cortex (BA 6) together with the frontal operculum support different
      functions during language processing. While BA 44/45 is seen to be increasingly
      activated whenever the internal re-construction of a hierarchical structure from
      a sequential input is necessary, BA 6 is involved in the processing of local
      structural dependencies. This functional differentiation is discussed in the
      context of the neurocytoarchitectonical differentiation between agranular
      structure characterizing BA 6 and a dysgranular cortical structure characterizing
      BA 44/45. This differentiation is exemplified in the domain of language, but is
      possibly applicable to non-language domains.

PMID- 16881253
TI  - Structure mapping and semantic integration in a construction-based
      neurolinguistic model of sentence processing.
AB  - The current research provides a theoretical, computational and neurophysiological
      framework in which particular aspects of sentence comprehension and non
      linguistic sequence transformation processing are implemented by a common neural
      mechanism for structure mapping. The theoretical context is derived from
      construction grammar theory in which language is considered in terms of a
      structured inventory of form to meaning mappings. Computationally, the
      construction grammar concept is implemented in a hybrid neural network model that
      is derived from functional neuroanatomical studies. In particular, based on data
      from Hoen et al. (2006, this issue), the generalized structure mapping capability
      is attributed to a local cortical network that includes Brodmann's area (BA) 44,
      while the integration of semantic structure into this transformation mechanism
      relies on BA 45.

PMID- 16881254
TI  - Is Broca's area part of a basal ganglia thalamocortical circuit?
AB  - The cortex constituting Broca's area does not exist in isolation. Rather, like
      other cortical regions, Broca's area is connected to other brain structures,
      which likely play closely related functional roles. This paper focuses on the
      basal ganglia, a set of subcortical structures that project through
      topographically organized "channels" via the thalamus to different frontal
      regions. It is hypothesized that the basal ganglia project to Broca's area. This
      circuitry is further posited to encompass at least two channels. One channel can
      be characterized as subserving procedural memory, while the other underlies the
      retrieval of knowledge from declarative memory. These hypotheses are supported by
      both anatomical and functional evidence. Implications and issues for further
      investigation are discussed.

PMID- 16881255
TI  - Hand actions and speech representation in Broca's area.
AB  - This paper presents data and theoretical framework supporting a new
      interpretation of the role played by Broca's area. Recent brain imaging studies
      report that, in addition to speech-related activation, Broca's area is also
      significantly involved during tasks devoid of verbal content. In consideration of
      the large variety of experimental paradigms inducing Broca's activation, here we
      present some neurophysiological data from the monkey homologue of Brodmann's
      areas (BA) 44 and 45 aiming to integrate on a common ground these apparently
      different functions. Finally, we will report electrophysiological data on humans
      which connect speech perception to the more general framework of other's action
      understanding.

PMID- 16881256
TI  - Broca's area: a supramodal hierarchical processor?
AB  - Despite the presence of shared characteristics across the different domains
      modulating Broca's area activity (e.g., structural analogies, as between language
      and music, or representational homologies, as between action execution and action
      observation), the question of what exactly the common denominator of such diverse
      brain functions is, with respect to the function of Broca's area, remains largely
      a debated issue. Here, we suggest that an important computational role of Broca's
      area may be to process hierarchical structures in a wide range of functional
      domains.

PMID- 16881257
TI  - Comparable mechanisms for action and language: neural systems behind intentions,
      goals, and means.
AB  - In this position paper we explore correspondence between neural systems for
      language and action starting from recent electrophysiological findings on the
      roles of posterior and frontal areas in goal-directed grasping actions. The paper
      compares the perceptual and motor organization for action and language, and
      discusses similarities between the impairments of apraxic and aphasic patients.
      Furthermore, based on the anatomical connectivity of Brodmann areas (BA) 44 and
      45 separate functional roles are proposed for the two constituent parts of
      Broca's area. The final part of the paper includes a discussion on the role of BA
      44 and neighboring areas in sequential processing for action and language.

PMID- 16881258
TI  - Dynamic anticipatory processing of hierarchical sequential events: a common role
      for Broca's area and ventral premotor cortex across domains?
AB  - This paper proposes a domain-general model for the functional contribution of
      ventral premotor cortex (PMv) and adjacent Broca's area to perceptual, cognitive,
      and motor processing. We propose to understand this frontal region as a highly
      flexible sequence processor, with the PMv mapping sequential events onto stored
      structural templates and Broca's Area involved in more complex, hierarchical or
      hypersequential processing. This proposal is supported by reference to previous
      functional neuroimaging studies investigating abstract sequence processing and
      syntactic processing.

PMID- 16881259
TI  - Beyond a single area: motor control and language within a neural architecture
      encompassing Broca's area.
AB  - In this position paper, we discuss a neural architecture comprising three major
      cortical systems: the inferior frontal cortex (including Broca's area), the
      rostral part of the posterior parietal cortex, and the superior temporal cortex.
      This network of areas is critical to imitation and to language. What are the
      functional properties of the network that make it possible for imitation and
      language to co-exist within the same neural architecture? We propose that this
      network implements cortical forward and inverse modeling for actions and speech
      sounds of self and others.

PMID- 16881260
TI  - A sentence is to speech as what is to action?
AB  - This article offers a conceptual framework for integrated analysis of
      subprocesses in action and language, based on goal-directed action. Anatomical
      substrates are discussed in the companion paper (Arbib and Bota, 2003) which
      approaches "Integrative Models of Broca's Area and the Ventral Premotor Cortex"
      within the context of explaining why the evolution of the human brain yielded
      mechanisms which support language in a multi-modal vocal-manual-facial system
      rather than privileging the vocal mode. Arbib and Bota (2003) examine homologies
      between different cortical areas in macaque and human to revisit the Mirror
      System Hypothesis (MSH) of Rizzolatti and Arbib (1998)--the notion that the
      mirror system for grasping (which has its frontal outpost in premotor area F5 of
      the macaque) provides the substrate for the evolution of the language-ready brain
      which supports parity of communication. They also offer a critique and extension
      based on the work of Aboitiz and Garcia (1997; Aboitiz et al., 2006). Arbib and
      Bota (2003) also discussed the utility of neuroinformatics in relating
      information across diverse cortical atlases and evaluating degrees of homology
      for brain regions of interest in different species (for discussion, see Deacon,
      2004; Arbib and Bota, 2004).

PMID- 16881261
TI  - What re-enactment earns us.
AB  - Evidence from both behavioural and brain studies suggests that perception of
      actions and their outcomes may induce (overt or covert) production of related
      actions in perceivers. Three views of the proper function of such re-enactment
      have been suggested: imitation, identification, and anticipation. Here I propose
      that the proper function of re-enactment is to subserve anticipation of upcoming
      action. Re-enactment exploits the motor system's inbuilt capacity to anticipate
      the consequences of action and extends it from the planning of own action to the
      perception of foreign action.

PMID- 16881262
TI  - Significance of Broca's area and ventral premotor cortex for music-syntactic
      processing.
AB  - This paper suggests that a cortical network comprising inferior frontolateral
      cortex [IFLC, corresponding to Brodmann's area (BA) 44], ventrolateral premotor
      cortex (vlPMC), and anterior superior temporal gyrus (aSTG) is involved in the
      processing of musical structure. This network presumably calculates harmonic
      relations between a chord and a preceding harmonic sequence, is involved in the
      detection of music-structural irregularities, and organizes fast short-term
      predictions of upcoming musical events.

PMID- 16881263
TI  - The ventral premotor cortex, corticospinal region C, and the origin of primates.
AB  - In addition to its projection to the brainstem, the ventral premotor cortex (PMv)
      sends axons directly to the upper cervical spinal cord in primates, with few
      terminations more caudally in either the cervical enlargement or in the
      lumbosacral spinal segments. This finding suggests that PMv plays a role in the
      control of head movements. Furthermore, comparative neuroanatomical studies
      indicate that PMv's corticospinal projection was a primate innovation. If the
      first primates adapted to an arboreal life that involved unimanual feeding, as
      some experts believe, then perhaps PMv's corticospinal projection evolved to
      coordinate head movements with this kind of feeding behavior. The computations
      underlying such control could later be adapted to control head orientation during
      social signaling.

PMID- 16881264
TI  - The anatomical segregation of the frontal cortex: what does it mean for function?
AB  - The frontal cortex consists of numerous areas, each with a special architecture
      (cyto-, myelo-, receptorarchitecture, etc.), connectivity and function.
      Quantitative tools of the analysis may assist in defining these cortical areas,
      and their position in a hierarchy of cortical regions and subregions. They enable
      a reliable definition of areal borders, and the consideration of intersubject
      variability. In our particular case, fMRI studies investigating certain aspects
      of cognitive control indicated to a rather circumscribed area in the posterior
      frontolateral cortex--the so-called IFJ area--which seems to correspond
      anatomically to a previously uncharted cortical area dorsally to area 44 as
      detected in histological sections of post mortem brains.

PMID- 16881265
TI  - Sign language processing and the mirror neuron system.
AB  - In this paper we review evidence for frontal and parietal lobe involvement in
      sign language comprehension and production, and evaluate the extent to which
      these data can be interpreted within the context of a mirror neuron system for
      human action observation and execution. We present data from three literatures-
      aphasia, cortical stimulation, and functional neuroimaging. Generally, we find
      support for the idea that sign language comprehension and production can be
      viewed in the context of a broadly-construed frontal-parietal human action
      observation/execution system. However, sign language data cannot be fully
      accounted for under a strict interpretation of the mirror neuron system.
      Additionally, we raise a number of issues concerning the lack of specificity in
      current accounts of the human action observation/execution system.

PMID- 16881266
TI  - Abstract grammatical processing of nouns and verbs in Broca's area: evidence from
      fMRI.
AB  - The role of Broca's area in grammatical computation is unclear, because syntactic
      processing is often confounded with working memory, articulation, or semantic
      selection. Morphological processing potentially circumvents these problems. Using
      event-related functional magnetic resonance imaging (fMRI), we had 18 subjects
      silently inflect words or read them verbatim. Subtracting the activity pattern
      for reading from that for inflection, which indexes processes involved in
      inflection (holding constant lexical processing and articulatory planning)
      highlighted left Brodmann area (BA) 44/45 (Broca's area), BA 47, anterior insula,
      and medial supplementary motor area. Subtracting activity during zero inflection
      (the hawk; they walk) from that during overt inflection (the hawks; they walked),
      which highlights manipulation of phonological content, implicated subsets of the
      regions engaged by inflection as a whole. Subtracting activity during verbatim
      reading from activity during zero inflection (which highlights the manipulation
      of inflectional features) implicated distinct regions of BA 44, 47, and a
      premotor region (thereby tying these regions to grammatical features), but failed
      to implicate the insula or BA 45 (thereby tying these to articulation). These
      patterns were largely similar in nouns and verbs and in regular and irregular
      forms, suggesting these regions implement inflectional features cutting across
      word classes. Greater activity was observed for irregular than regular verbs in
      the anterior cingulate and supplementary motor area (SMA), possibly reflecting
      the blocking of regular or competing irregular candidates. The results confirm a
      role for Broca's area in abstract grammatical processing, and are interpreted in
      terms of a network of regions in left prefrontal cortex (PFC) that are recruited
      for processing abstract morphosyntactic features and overt morphophonological
      content.

PMID- 16881267
TI  - Broca's area and inflectional morphology: evidence from broca's aphasia and
      computer modeling.
AB  - In a series of articles Ullman (2001, 2004; Ullman et al., 1997) has proposed
      that regular inflection is critically subserved by Broca's area. This suggestion
      is motivated by the finding that English speaking Broca's aphasics show selective
      deficits with regular inflection. Here we argue that this proposal does not hold
      cross-linguistically but is based on a confound between inflectional suffix and
      regularity that is specific to the English language. We present data from two
      experimental studies of participle inflection with 13 German and 12 Dutch Broca's
      aphasics. None of these aphasic speakers are selectively impaired for regular
      inflection but instead most of them show selective deficits with irregular
      inflection. These data suggest that a selective regular deficit is not a
      characteristic of Broca's aphasia across languages, and that Broca's area is not
      critically involved in regular inflection. To investigate the nature and
      localization of the processes underlying inflection we present a connectionist
      neural network model that accounts for the deficits of the German aphasic
      speakers. The model implements the view that the inflection of all verb types is
      based on a single mechanism with multiple representations that emerge from
      experience-dependent brain development. We show that global damage to this model
      results in a selective deficit for irregular inflection that is comparable to
      that of the German aphasic speakers. This finding suggests that a selective
      impairment of irregular participles as observed by German and Dutch aphasic
      speakers does not presuppose two distinctly localized mechanisms or processes
      that can be selectively affected by brain damage.

PMID- 16881269
TI  - Determinants of bold signal correlates of processing object-extracted relative
      clauses.
AB  - Event-related functional magnetic resonance imaging (fMRI) was used to
      investigate the determinants of blood oxygenation level-dependent (BOLD) signal
      correlates of processing relative clauses. Matched pairs of sentences that
      differed in their processing demands were compared. One member of the pair
      consisted of a syntactically simpler object-subject (OS) sentence, containing a
      subject-relativized clause attached to the object noun phrase. The second member
      of the pair consisted of a syntactically more complex subject-object (SO)
      sentence, containing an object-relativized clause attached to the subject noun
      phrase. Participants made plausibility judgments about the sentences in whole
      sentence visual presentation. Voxel-wise statistical activation maps showed
      increased BOLD signal in multiple cortical regions for complex compared to simple
      syntactic structures. This pattern was found for plausible sentences only and,
      within the set of plausible sentences, for SO sentences in which the head noun of
      the relative clause was animate and the subject noun of the relative clause was
      inanimate. These results require a re-interpretation of previous results with the
      same materials using positron emission tomography.

PMID- 16881268
TI  - A functional neuroimaging investigation of the roles of structural complexity and
      task-demand during auditory sentence processing.
AB  - Using functional magnetic resonance imaging (fMRI), this study directly examined
      an issue that bridges the potential language processing and multi-modal views of
      the role of Broca's area: the effects of task-demands in language comprehension
      studies. We presented syntactically simple and complex sentences for auditory
      comprehension under three different (differentially complex) task-demand
      conditions: passive listening, probe verification, and theme judgment. Contrary
      to many language imaging findings, we found that both simple and complex
      syntactic structures activated left inferior frontal cortex (L-IFC). Critically,
      we found activation in these frontal regions increased together with increased
      task-demands. Specifically, tasks that required greater manipulation and
      comparison of linguistic material recruited L-IFC more strongly; independent of
      syntactic structure complexity. We argue that much of the presumed syntactic
      effects previously found in sentence imaging studies of L-IFC may, among other
      things, reflect the tasks employed in these studies and that L-IFC is a region
      underlying mnemonic and other integrative functions, on which much language
      processing may rely.

PMID- 16881270
TI  - When Broca experiences the Janus syndrome: an ER-fMRI study comparing sentence
      comprehension and cognitive sequence processing.
AB  - The determining of brain regions that exhibit specific activity during sentence
      comprehension compared to other non-linguistic cognitive tasks constitutes one of
      the important challenges in the domain of functional neuroimaging of the faculty
      of language. In the current paper we report an event-related functional magnetic
      resonance imaging (ER-fMRI) experiment, in which we directly compared the
      cerebral basis of sentence comprehension on the one hand, and of abstract
      sequence processing on the other hand. Previous experimental work done in our
      group, as well as different observations from recent behavioural,
      neurophysiological and functional neuroimaging experiments led us to propose the
      hypothesis that both of these tasks would share certain computational properties.
      Thus, this experiment was designed to show which brain regions would be
      implicated in both tasks and compare them to brain regions that would be
      specifically engaged in sentence comprehension. Results from this experiment
      suggest that distinct sub-regions in the left prefrontal cortex, potentially
      including Broca's area show distinct activation patterns during both of these
      tasks. Results are discussed in the context of a construction-based model of
      sentence processing (see Dominey and Hoen, 2006, this issue) that is based on a
      dual-path processing mechanism separating function and content information
      processing. We propose and discuss the hypothesis that subparts of Broca's area
      BA 44 and BA 45 would respectively be implicated in two different aspects of
      sentence comprehension: i) a general structure mapping capability and ii) the
      online integration of semantic representations onto structural constraints.

PMID- 16881271
TI  - Specific reading and phonological processing deficits are associated with damage
      to the left frontal operculum.
AB  - Functional neuroimaging studies in normal subjects indicate that a region in the
      left frontal operculum (FO) is more active when subjects read pronounceable
      nonwords as compared to most word types. Here, we report convergent evidence on
      this finding using the lesion method. We tested the prediction that subjects with
      left FO damage would have impaired reading of pronounceable nonwords, but
      relatively intact reading of most word types. Eleven target subjects with
      circumscribed left FO lesions, and two comparison groups of either brain-damaged
      or normal subjects matched to the target subjects for age, sex, handedness, and
      education, were studied using reading tasks derived from previous neuroimaging
      work. As predicted, the FO group was significantly less accurate than the
      comparison groups at reading nonwords. By contrast, the FO subjects showed
      relatively intact word reading, a pattern consistent with the syndrome of
      "phonological dyslexia". The FO subjects, however, did exhibit particular
      difficulty reading low frequency words with inconsistent grapheme-to-phoneme
      correspondences (e.g., PINT), which parallels the finding from functional imaging
      studies that reading such items produces more activation in left FO than reading
      high frequency words and low frequency words with consistent grapheme-to-phoneme
      correspondences (e.g., JADE) (Fiez et al., 1999). In several follow-up
      experiments, we found that the FO subjects were also impaired on other
      phonological tasks that have been associated with left frontal opercular
      activation in functional neuroimaging studies. The findings converge nicely with
      extant functional imaging work, and provide further evidence that regions within
      the left FO are part of a system that makes specific and critical contributions
      to some of the phonological processes that support reading.

PMID- 16881272
TI  - Functional neuroanatomy of segmenting speech and nonspeech.
AB  - This fMRI study investigates the extent to which frontal brain activation
      observed during speech discrimination is due to processes specific to
      articulatory recoding of speech or is due to segmenting and comparing portions of
      any continuous acoustic stimuli. A set of ten participants performed
      same/different judgments on the first speech sound in pairs of consonant-vowel
      consonant (CVC) syllables or the first tone in pairs of sequences of three tones.
      Comparison between speech and tone tasks demonstrated significant bilateral
      temporal activation, which was associated with differences in perceptual analysis
      of complex acoustic stimuli. Both speech and tone tasks also showed significant
      activation in the left inferior frontal gyrus (IFG) compared to baseline. These
      results suggest that portions of the left prefrontal cortex may be important for
      selecting and comparing auditory stimuli for decision, but may not be
      specifically related to speech.

PMID- 16881273
TI  - Left-right asymmetry in volume and number of neurons in adult Broca's area.
AB  - Total neuron number in, and volume of, Brodmann areas (BA) 44 and 45 (Broca's
      area) were studied in Nissl-stained sections from the left and right hemispheres
      of five adult men and five adult women. The volume of BA 44 was greater in the
      left hemisphere than in the right in all ten cases, although asymmetry was only
      significant for the subgroup of male subjects. For six of the ten subjects
      (including all females), the volume of BA 45 was greater in the left hemisphere
      than the right. This asymmetry was significant only for the women. A significant
      left-over-right asymmetry has been found in total neuron number in male BA 44.
      Although the total number of neurons in left BA 45 was larger in all five female
      subjects, this asymmetry did not reach significant difference. In the male
      subjects no significant asymmetry difference in total neuron number was found in
      BA 45 either. There was no significant hemispheric asymmetry or gender
      interaction for neuronal number density, either in BA 44 or 45. This study is the
      first quantitative study of total number of neurons in BA 44 and 45 in adult
      subjects, and demonstrates that both the volume and the total neuron number of BA
      44 and 45 on the left are generally greater than that of the right hemisphere,
      with the possible exception of the male BA 45. In addition, it shows that the
      inter-individual variability was also very large (more than twofold) in the
      numerical values of all variables.

PMID- 16881274
TI  - [Bilirubin injuries among newborn infants can be prevented. New tools keep the
      zero vision alive].

PMID- 16881275
TI  - [Abdominal aortic aneurysm screening starts now. First out with the invitation of
      all 65-year old men is the county of Uppsala].

PMID- 16881276
TI  - [Best working climate in private or investor-owned hospitals. Physicians'
      experiences with different management forms].

PMID- 16881277
TI  - [Long-term treatment with interferon-alpha can induce sarcoidosis. The connection
      can be stronger than earlier believed].

PMID- 16881278
TI  - [Exertional heat stroke caused severe hepatic and renal failure. Liver dialysis
      by means of MARS tested for the first time in this setting].

PMID- 16881279
TI  - [Anterior abdominal wall hernia].

PMID- 16881280
TI  - [A critical question: Therapeutic effect or regression towards the mean?].

PMID- 16881281
TI  - [How to be confident as an executive officer. Good and confident leadership no
      utopia in current Swedish, regulated health care].

PMID- 16881283
TI  - [WHO's annual report is about personnel--but who pays the costs?].

PMID- 16881282
TI  - [Colorectal cancer--a pan-Nordic study about the value of colonoscopy screening
      is required].

PMID- 16881284
TI  - [Why has the physician's labor union nothing more to say about the abortion issue
      than "we support the proposal"?].

PMID- 16881285
TI  - [Regular surveys of elderly persons' medications have positive effects].

PMID- 16881286
TI  - [Fear of responsibility].

PMID- 16881287
TI  - [The way to hell with the help of IT].

PMID- 16881288
TI  - [Physicians who slander each other hurt the patients!].

PMID- 16881289
TI  - [Women's fates in Africa and India--perspectives in the gender debate].

PMID- 16881290
TI  - [Aqua florum omnium, clove drops and other prescription curiosities by Linne].

PMID- 16881291
TI  - [Effects of nitrogen fertilization on carbon balance in the freshwater marshes].
AB  - To understand the influence of nitrogen fertilization on the carbon balance in
      the freshwater marshes, we measured the CO2 and CH4 emissions as well as net
      ecosystem exchange (NEE) of CO2 using the static chamber and gas chromatogram
      technique in situ over Deyeuxia angustifolia wetland in Sanjiang Plain. Results
      from the field observed indicated that fertilization increased the biomass and
      gross primary productivity (GPP) as well as the CO2 and CH4 emissions, while
      decreased the net ecosystem exchange of CO2 but not change the seasonal dynamics
      of CO2 and CH4 emissions as well as the NEE. Seasonal amount of CO2 and CH4
      emission from the fertilization was respectively 34% and 145 % higher than that
      from the control, while the NEE and net carbon exchange decreased 70% and 81.6%
      due to the nitrogen fertilization. During the whole growing season of 2004 the
      ecosystem still showed the net uptake of the carbon not only in the fertilization
      treatment but also control. Thus, it can be assumed that nitrogen fertilization
      decreased the net carbon uptake from the atmosphere but not changed the ecosystem
      from a carbon sink to a source.

PMID- 16881292
TI  - [Effect of organic material incorporation in rice season on N2O emissions from
      following winter wheat growing season].
AB  - In a field experiment, five fertilizer treatments including chemical fertilizer
      (CF), rapeseed cake + chemical fertilizer (RC + CF), wheat straw + chemical
      fertilizer (WS + CF), cow manure + chemical fertilizer (CM + CF), and pig manure
      + chemical fertilizer (PM + CF), were dedicated to examine the effect of organic
      materials incorporation in the rice season on N2O emissions from the following
      winter wheat season and to assess the climatic impacts from CH4 and N2O emissions
      in a rice-wheat rotation. Organic material was incorporated at the same rate (225
      g x m(-2)) for organic treatments at the depth of 10 cm in the soil as the basal
      fertilizer just before rice transplanting. An identical synthetic nitrogen
      fertilizer was adopted for all treatments. Results show that the seasonal amount
      of N20 emissions from the following wheat season differed with organic material
      applied in rice season. No pronounced difference in N20 emissions was found
      between the CF and RC + CF treatments. In contrast with the CF treatment,
      however, N2O emission was decreased by 15% for the WS + CF treatment, but
      increased by 29% and 16% for the CM + CF and PM + CF treatments, respectively.
      Over the entire annual rotation cycle, N2O amount was increased by 17% for the CM
      + CF treatment, 7% for the PM + CF treatment, and 6% for the RC + CF treatment,
      but decreased by 16% for the WS + CF treatment in comparison with the CF
      treatment. Based on total emissions of CH4 in rice season and N2O over the entire
      rotation cycle, the estimation of combined Global Warming Potentials (GWPs) for
      CH4 and N20 shows that over a 20 years horizon or a 500 years horizon, the value
      of annual total GWPs was ranked in the order of RC + CF > WS + CF > CM + CF > PM
      + CF > CF or RC + CF > CM + CF > PM + CF > WS + CF > CF. The highest, middle and
      the lowest value of the GWPs per unit crop grain yield occurred for the crop
      residue, farmyard manure and pure synthetic fertilizer treatments, respectively.
      Compared to the chemical fertilizer treatment, accordingly, organic material
      combined with chemical fertilizer application in rice season increased climatic
      impacts from CH4 and N20 emissions in a rice-winter wheat rotation system.

PMID- 16881293
TI  - [Characteristics of polycyclic aromatic hydrocarbons (PAHS) on airborne
      particulates in Beijing].
AB  - Total suspended particulates (TSP) samples were collected from Sep., 2003 to
      Jul., 2004 in Beijing, and 15 kinds of PAHs, ranging from 3 to 7 rings were
      analyzed. The maximum concentrations sigma PAHs and BaP were 705 ng/m3 and 52
      ng/m3 respectively. Average sigma PAHs concentrations in four seasons were 46
      ng/m3, 16 ng/m3, 52 ng/m3 and 268 ng/m3 respectively; and the average BaP
      concentrations in four seasons were 2.8 ng/m3, 0.23 ng/m3, 3.3 ng/m3, 16 ng/m3
      respectively. Regarding to the meteorological parameters, precipitation
      distinctly lowered the concentration; in heating period, PAHs concentrations fall
      with the temperature goes up, but there is no obvious relation between
      concentration and temperature in non-heating period; the increase of wind speed
      level causes the decrease of PAH concentrations in the heating period, but
      relation between PAH concentrations and wind speed varied with aromatic rings of
      PAHs and levels of wind speed in the non-heating period.

PMID- 16881294
TI  - [Ozone pollution, influence factors and their correlation at urban area in
      summer].
AB  - Based on the observational data of near surface O3, NO, NO2, CO and
      meteorological factors in the urban area of Ji'nan during summer 2003, the 03
      concentrations and their temporal variation characteristics were studied. The
      correlation between O3 and its precursors (NO, NO2, CO) and related
      meteorological factors (solar radiation, temperature) was analyzed. The results
      show that O3 pollution during summer was very serious in Ji'nan, and the levels
      of O3, NO, NO2, NOx and CO were quite high during the observational period. O3
      concentrations were well negatively correlated with NO, NO2, NO, and CO during
      day time. As to the meteorological factors, O3 concentrations correlated well
      with solar radiations, but showed no obvious correlation with the temperatures.
      Consequently, based on the above data and results, a regression equation that
      relates ozone concentrations observed in the day time to its precursors and solar
      radiation was constructed. The results show that the calculated values were in
      good agreement with the observed values.

PMID- 16881295
TI  - [Removal of SO2 from flue gas by water vapor DC corona discharge].
AB  - The influence of several factors on removal rate of SO2 from flue gas in
      unsaturated water vapor DC corona discharge was researched. Furthermore, the
      experiments of the removal rate of SO2 in pulsed discharge increased by water
      vapor DC corona discharge plasma were conducted. The experiment system is
      supplied with multi-nozzle-plate electrodes and the flow of simulated flue gas is
      under 70 m3/h. The results show that removal rate of SO2 can be improved by
      increasing the concentration of water vapor, intensity of electric field or
      decreasing flow of simulated flue gas. In unsaturated water vapor DC corona
      discharge, removal rate of SO2 can be improved by 10%, when NH3 is added as NH3
      and SO2 is in a mole ratio of two to one, it can reach 60%. The removal rate of
      SO2 can be increased by 5% in pulsed corona discharge and reach above 90%.

PMID- 16881296
TI  - [Integrated model of nutrients for the Miyun Reservoir and its watershed].
AB  - In recent years, the Miyun Reservoir faces severe problems of water quality and
      quantity due to continuous drought. In order to simulate and predict the
      eutrophic status of the Miyun Reservoir and its watershed, an integrated model
      was developed based on GIS and RS technology, which was composed of non-point
      source (NPS) simulation model, aquatic ecological-hydrodynamic model, and river
      water quality model. Ecological-hydrodynamic model was developed through coupling
      water quality analysis simulation program (WASP) with environmental fluid
      dynamics Code (EFDC). SWAT was selected as NPS simulation model, which could also
      perform water quality simulation in the river. Then the integrated model was
      calibrated using Markov Chain Monte Carlo method and verified using observed
      data. Results indicated that observed water quality data laid around the mode
      curves of simulation distribution, and which also dropped into the confidence
      interval on 80 percent credibility of water quality simulation distribution. In
      conclusion, the results show that the integrated model can meet the need of
      application.

PMID- 16881297
TI  - [Continuously modeling research on the transfer and transform processes of
      phosphorus in Heihe River watershed].
AB  - Taking supply water source of Xi'an city as an example, by the help of Matlab
      software, using fill and yield model, the Inverse-Gauss flow concentration model,
      runoff-sediment relation model and Viney model, the transfer and transform
      processes of phosphorus from 1981 to 1990 were modeled continuously. Phosphorus
      pollution loads of Heihe River were also estimated. The result shows that the
      continuous modeling result accorded with the generic law of phosphorus loss. The
      relative error between modeling result and monitor interpolation result was not
      more than +/-30%. So the modeling method proposed in this paper could be used to
      model continuously the transfer and transform processes of phosphorus in Heihe
      river watershed. This study was only primary attempt to non-point source
      pollution continous model, therefore, the modeling method needed to be improved
      and perfected further.

PMID- 16881298
TI  - [Three stages of the groundwater chemical properties reacting on the intermittent
      water deliveries in lower Tarim River, China].
AB  - Based on the monitored data of groundwater chemical properties and groundwater
      depth influenced by five intermittent water deliveries in the lower reaches of
      the Tarim River, the regulation of groundwater chemistry varying was analysed,
      the variations in groundwater chemical properties unfolded a clear three-stages
      changing character under the influence of water deliveries: the initial stage-
      concentrations of major ions and total dissolved solids (TDS) increasing; the
      intermediate stage-the concentrations decreasing; the late stage--the chemical
      properties increasing once more. The variation of groundwater chemistry resulted
      from many factors, such as the salinities in soil profile, the quality of
      transported water, the distance from watercourse, the amount and the season of
      the delivery. However, "salts coming with the water flow, and leaving with it" is
      the main reason that led to the increase and decrease of chemical properties at
      first stage and second stage, and with the uprising water level, more and more
      salinities in soil profile dissolved into ground water and the severe evaporation
      resulted the concentrations of major ions and TDS increase at late stage.
      Furthermore, the variations of groundwater chemistry at the intermission of water
      deliveries have close relationship to the three stages. It should be pointed out
      that the mode of water transport in surface scope is infeasible due to the
      climate characteristics of the lower reaches of the Tarim River.

PMID- 16881299
TI  - [Hydrochemical characteristic analysis of melting water flow in Keqikaer Glacier,
      Tianshan (west) Mountains].
AB  - In order to study the melting water chemical characteristics in the Keqikaer
      Glacier, Tianshan(west)Mountains, the samples were collected from June to
      September in 2003. The result is found that: (1) The pH value is between 7.35
      8.52, the order of which is:river water > glacier melting water > lake water on
      glacier > precipitation. (2) The various ionic concentrations of melting water
      are lower than other three kinds of samples, and average is 24% of river water.
      (3) Comparing and analyzing hydrochemical difference among various precipitation
      forms, the author found that inhomogeneous ionic concentration of rainwater is
      higher than the others. (4) Next, the water samples at different altitude have
      been analyzed, which shows that inhomogeneous ionic concentration of altitude
      effect is very remarkable. It is expected that if altitude is lower, the
      eluviation is led by glacier melting can influence the enviro-information record
      of ice layer.

PMID- 16881300
TI  - [Soil carbon and nitrogen sequestration following cropland to forage grassland
      conversion in the marginal land in the middle of Heihe River basin, northwest
      China].
AB  - Changes in soil organic carbon (SOC) and total nitrogen (TN) stocks were studied
      following croplands were converted to forage grasslands (alfalfa) for five years
      on the marginal land at the edge of oasis in the middle reaches of Heihe river
      basin. Soil from 12 paired forage land/adjacent cropland on the two soil types
      (Typic Torripsamments and Typic Calciorthids) was sampled at the three depths of
      0-5, 5-10 and 10-20 cm and analyzed for SOC and TN, particulate organic carbon
      (POC) and nitrogen (PON). The studied soils had very low SOC and N
      concentrations. SOC stock at the 0-20 cm depth increased by 22.1%-27.8% after
      conversion of annually crop to perennial alfalfa for four years, and carbon
      sequestration rate was estimated to be on average 0.47 Mg/(hm2 x a). The greatest
      change in SOC stock occurred at the 0-5 cm surface layer with an increase of 32%
      66%. No significant TN stock was found at the 0-20 cm depth, however, it
      increased at the 0-5 cm surface layer by 12.8% and 48.1% for Typic Torripsamments
      and Typic Calciorthids, respectively. Changes in POC and PON stocks were more
      significant than those in SOC and total N following conversion of crop to forage,
      and the percentage of distributions of POC and PON increased. POC and PON stocks
      at the 0-20 cm depth increased by 22.8%-42.7% and 18.6%-57.6% with the greatest
      increases at the 0-5 cm layer. The increase in soil C pool was mainly attributed
      to the increase of POC formation after the marginal lands converted to perennial
      forage cover. Typic Calciorthids with lower SOC concentration had relatively
      lower C sequestration rate but more significant effects of C and N sequestration
      compared with Typic Torripsamments.

PMID- 16881301
TI  - [Change of farmland soil organic carbon content in typical region in Hunan
      Province].
AB  - Taking Yuanjiang City (112 degrees 16' - 112 degrees 56' E, 28 degrees 42' - 29
      degrees 11' N) in Hunan Province as an example, the changes of soil organic
      carbon content and its distribution in farmland soils in Dongting Lake region
      were investigated, based on the dense sampling in typical plots and the
      investigation of historical materials. The results showed that soil organic
      carbon in different land uses and cropping systems, such as rice/rice, rice,
      paddy-upland rotation, increased stably, but soil organic carbon in dry land
      induced in some extent. Mean soil organic carbon content in farmland soils of the
      typical sampling region in 2004 was (26.66 +/- 4.93)g x kg(-1). Compared with
      that in 1979,soil organic carbon content increased by 22.64%. In 1979,soil
      organic carbon content in paddy soil mainly ranged from 20 g x kg(-1) to 25 g x
      kg(-1) (frequency is 62.5% in all sampling plots), and in 2004 increased to 20-35
      g x kg(-1) (frequency is 88.0%). This indicated that soils under different types
      of land use in Dongting Lake region could all store carbon, and organic carbon
      pool in farmland soils would play "sink" role in the cycle of atmosphere CO2.

PMID- 16881302
TI  - [Dynamics of heavy metals in the holocene aeolian loess-soil profile in the upper
      reaches of the Huaihe River].
AB  - Upon the exploration and research in the field, we determined the content of Pb,
      Zn, Cu, Mn, Cr, Co, Ni, Ti, V, Nb at YPC loess-soil site on the X-ray
      Fluorescence. In the stage of loess accumulation, the content of these heavy
      metals are very low and the variances are very little, which can be served as the
      background value of paleosol formation. In the stage of Holocene Megathermal, the
      content of these heavy metals are increased greatly, because the eluviations and
      transmigrations of freely soluble elements under warm and humidity environment.
      In the stage of modern soil( MS), the content of Pb are increased gradually, and
      there are abruptly increase in the depth of 8cm below the ground, which are the
      records of sedimentation and accumulation of atmospheric pollutant.

PMID- 16881303
TI  - [Preparation and photocatalytic activity of boron doped CeO2/TiO2 mixed oxides].
AB  - Boron doped CeO2/TiO2 mixed oxides photocatalysts were prepared by adding boric
      acid and cerous nitrate during the hydrolyzation of titanium trichloride and
      tetrabutyl titanate. XRD, UV-Vis DRS and XPS techniques were used to characterize
      the crystalline structure, light absorbing ability and the chemical state of
      Boron element in the photocatalyst sample. The photocatalytic activities were
      evaluated by monitoring the degradation of acid red B under UV irradiation. These
      results indicate that the wavelengths at adsorbing edge are affected by the
      content of cerous nitrate and the maximum absorption wavelength is about 481 nm
      when the mole ratio of Ce/Ti is 1.0. For higher dosage of Cerium, the absorbance
      edge shifts to blue slightly. The prepared photocatalyst is composed of anatase
      TiO2 and cubic CeO2 when calcined at 500 degrees C. An increase in the
      calcination temperature transforms the crystalline structure of the titanium
      oxides from anatase to rutile, and has no obvious influence on crystalline
      structure of CeO2 but crystallites growth up. The absorbance edge decreases
      drastically with the increase of calcination temperature. With a view to the
      stability of photocatalyst and utilization of sun energy, 500 degrees C of
      calcination temperature is recommended. The XP spectrum for B1s exhibits that
      only a few boron ions dope into titania and ceria matrix, others exist in B2O3.
      The photocatalytic activity increases with increase of cerous nitrate dosage, and
      decreases drastically due to higher dosage (the mol ratio of Ce/Ti > 0.5). After
      10 min UV irradiation, 96% of acid red B is degraded completely over
      photocatalyst under optimum reaction condition.

PMID- 16881304
TI  - [Experimental study on the treatment of low level radioactive waste water by
      inorganic nanofiltration membrane].
AB  - Soluble sodium poly(acrylic) acid (NaPAA) with molecular weight of 2000-5000 was
      selected as an assistant reagent of inorganic nanofiltration membrane which was
      used to treat low level radioactive waste water mainly containing radionuclides
      90Sr, 137Cs and 60Co. The effect of non-active simulated wastewater pH and NaPAA
      concentration on the retention efficiency of non-active nuclides strontium,
      cesium and cobalt ions and membrane permeation flux were explored, and the effect
      mechanism was also preliminarily discussed. The optimum process parameters were
      decided: pH 7-8, NaPAA volume concentration no lower than 0.1%. Real radioactive
      waste water was treated under optimum experiment condition. The results show that
      the decontamination efficiency of total beta and gamma emitters of low-level
      radioactive wastewater were both up to about 95% by inorganic nanofiltration
      assisted by NaPAA, and the permeation flux was also satisfying.

PMID- 16881305
TI  - [Effect of limited aeration on the thermophilic anaerobic treatment of high
      sulfate refractory wastewater].
AB  - A thermophilic up-flow anaerobic sludge blanket (UASB) reactor was used to treat
      high-sulfate refractory wastewater from a sulfite pulp mill. The microorganisms
      were inhibited significantly as the result of sulfate reduction. Based on the
      consideration that the limited aeration may strip hydrogen sulfide out and
      oxidize part of the sulfide into nontoxic elemental sulfur, limited aeration was
      introduced into the reactor later to reduce the inhibition. The reactor showed
      much better running stability and higher treatment capacity thereafter. COD
      removal increased from 40%-50% to 60%-70% when the organic loading rate (OLR) was
      doubled. This study verified that some methanogens could be aerotolerant while
      some of the fermentation bacteria might be sensitive to the incomplete anaerobic
      surroundings.

PMID- 16881306
TI  - [Determination for optimal ozone dose in O3-BAC].
AB  - The ozonation can increase biodegradability of water and the biofilter after
      ozonation can increase biostability of water. The result shows that with
      different doses of ozone between 2 and 8 mg/L, ozonation can increase AOC-P17,
      AOC-NOX and BDOC by 20.9%-85.5%, 42.1%-158.2% and 21.4%-84.4%, respectively. The
      optimum ozone dose for maximum AOC and BDOC formation is 3 mg/L. In the test, the
      AOC of effluent from BAC is lower than 50 microg/L (acetate-C). The AOC
      concentration is between 35.9 and 46.6 microg/L (acetate-C), and the effluent
      belongs to biostability.

PMID- 16881307
TI  - [Effect of activated sludge properties on short-term membrane fouling in
      submerged membrane bioreactor based on statistical analysis].
AB  - The influence of activated sludge properties on membrane fouling was investigated
      using statistical method. The results show that extracelluler polymeric
      substances (EPS), soluble microbial products (SMP), suspended solids in the
      supernatant (SSs), dynamic viscosity (micro), relative hydrophobicity (RH) and
      Zeta potential all have a significant influence on membrane permeability during
      microfiltration of activated sludge wastewater. The pearson's correlation
      coefficient (r(p)) for linear correlations between membrane fouling resistance
      and these sludge properties are 0.898, 0.712, 0.810, 0.691, 0.837, -0.881,
      respectively. The statistical results also show that SMP, micro, SSs, Zeta
      potential, and RH are mostly determined by EPS, indicating that EPS is the main
      and essential factor affecting membrane fouling in activated sludge properties.
      The pearson's correlation coefficient (r(p)) for linear correlations between
      total EPS and other sludge properties are 0.682, 0.633, 0.783, -0.953, 0.877,
      respectively. EPS should be controlled in the operation of membrane bioreactor to
      achieve a suitable permeation.

PMID- 16881308
TI  - [Main reactions in anaerobic ammonium oxidation reactor under organic carbon
      condition].
AB  - The main reactions occurred was studied in five ASBRs (1-5) which had run at
      steady ANAMMOX. The organic carbon condition was kept up by means of the addition
      of glucose in the wastewater. The results reveal that aerobic nitrifing bacteria,
      denitnifying bacteria and ANAMMOX bacteria could coexist, and the aerobic
      nitrification reaction, the ANAMMOX reaction and the denitrification reaction
      could occur according to certain order in the reactors. The optimal ANAMMOX
      performance was achieved in reactor 1 which C/NH4+ -N was 1.7. On hour 41, COD
      removal, NH4+ -N removal and NO2- -N removal in reactor 1 were 100%, 81.7% and
      74.4%, respectively.

PMID- 16881309
TI  - [Impact of pH on the generation of COD, phosphorous and ammonia-nitrogen during
      the anaerobic fermentation of excess activated sludge].
AB  - There are mainly two kinds of sludge in the municipal wastewater treatment plant,
      i. e. , primary and secondary sludge. This study investigated the effect of pH,
      ranging from 4.0-11.0, on hydrolysis in terms of soluble chemical oxygen demand
      (SCOD) production in the anaerobic solubilization of excess activated sludge at
      20-22 degrees C. It was found that when the value of pH was 8.0-10.0, the
      production quantity of SCOD were higher than pH = 5.0-7.0. Especially when the pH
      was 10.0 or 11.0, the value of SCOD was almost 10 times of pH = 6.0 during the
      whole fermentation of 20 days. And volatile fatty acids (VFA) production on the
      8th day under alkaline condition was higher than that under acidic condition.

PMID- 16881310
TI  - [Experimental study on the mechanism of oilfield wastewater treatment by using
      hydrolysis-acidification with aerobic biological processes].
AB  - Hydrolysis-acidification + aerobic biological processes were conducted
      experimentally to treat oilfield wastewater pretreated with physical and chemical
      treatment in Xinjiang oilfield. The results showed that when the COD
      concentration in influent was 190-220 mg x L(-1), that in effluent reduced to 65
      75 mg x L(-1) under HRT of 10h in both hydrolysis-acidification process and
      aerobic biological process, reaching the strictest requirement of Effluent
      Standards for Wastewater from Petroleum Development Industry (GB3550-83). Using
      GC/MS technology, the relative content of various organic pollutants was analyzed
      to discover the transfer and degradation law in the oilfield wastewater in
      biological treatment process. The system of DNA extraction technique, PCR and
      DGGE reacting systems were practical to analyze the microbial community in the
      hydrolysis-acidification and aerobic biological processes. The predominant
      sequences of several 16S rDNA DGGE fragments were determined and confirmed in
      comparison in GeneBank (NCBI).

PMID- 16881311
TI  - [Study on pretreatment of saponin wastewater by water hyacinthy].
AB  - The pretreatment of the saponin wastewater by water hyacinth (Eichhornia
      crassipe) was studied. With contrast experiments, the results indicate that after
      8 h adsorption by the dry air cells of water hyacinth, the concentration of
      chlorine ion in the saponin wastewater reduce 10%, chroma reduce 97.2%, pH change
      from 1.09 to 1.26, COD removal efficiency is 20%. The results indicate that the
      pretreatment process can improve biodegradability of the saponin wastewater, the
      biogas rate is 1.5 multiple than before , resulting in the benefit to the follow
      up biological treatment. After the adsorption, water hyacinth biogas fermenting
      also improvement which is used for improve the effect of fermentative.

PMID- 16881312
TI  - [Effects of Pb(NO3)2 and cetylpyridinium chloride on sorption of p-nitrophenol by
      sediment].
AB  - Sorption behavior of p-nitrophenol by sediment in the presence of both
      cetylpyridinium chloride (CPC) and Pb(NO3)2 were investigated. The concurrence of
      Pb(NO3)2 inhibited the enhancement of sorption induced by CPC. The removal effect
      of pnitrophenol from sediment by compounding of CPC and Pb(NO3)2 presented
      antagonistic effect. At a given concentration of CPC, the antagonistic effect
      increased with increasing of the initial concentration of Pb(NO3)2. The
      antagonistic effect was also dependent on CPC concentrations. At the initial
      concentration below 3000 mg/L(the equilibrium concentration was below CMC), the
      antagonistic effect was especially significant. With the increase of the
      concentration of CPC, the antagonistic effect decreased gradually. Especially at
      the higher concentration above CMC, the effect went to be an independent effect
      just induced by CPC. In addition, the study also indicate that Pb2+ and CPC may
      not compete for the same adsorption sites.

PMID- 16881313
TI  - [Competitive sorption of mixed organic pollutants by soils].
AB  - Binary sorption equilibria were measured using three different loading methods:
      METHOD (1): Naphthalene loaded before phenanthrene; Method (2): Both Solutes
      loaded simultaneously; Method (3): Naphthalene loaded after phenanthrene. Each
      having 110 reactors and 10 levels of initial concentrations for both tested
      organic solutes. This is very different from previous studies which employed one
      single initial concentration of the primary solute and multiple concentration
      levels of the competitor and loaded both solutes simultaneously. Results indicate
      that the adsorption behavior of the same solute on the same sorbent with
      competing solute is distinctly different from its single adsorption behaviors.
      Naphthalene isotherm becomes more linear as phenanthrene concentration increases
      in the binary systems tested using all three loading methods. In contrast,
      phenanthrene isotherm remains nonlinear when it was loaded after or loaded
      simultaneously with naphthalene. It becomes more linear as a function of
      naphthalene concentration only when phenanthrene was loaded before naphthalene.
      The Koc values decrease as a function of competing solute concentration (c(e)),
      and approach to the lowest value when this c, is about 0.5 Sw. IAST provides
      better predictions for the sorption only when the competing solute is at lower
      c(e)(< 0.01 Sw). Large-size and more hydrophobic phenanthrene competes favorably
      with the small-size and relatively less hydrophobic naphthalene, and the
      heterogeneity of natural organic matter associated with the soil may have strong
      influence on the competitive phenomena between the tested solutes.

PMID- 16881314
TI  - [Environmental behavior in wetland soil of organic chlorine from pulp bleaching
      wastewater].
AB  - The adsorption equilibrium and leaching characteristics of organic chlorine on
      soils were studied by mean of soil column method using bleaching water in
      laboratory condition. Soil samples were also collected from the wetland that
      irrigated with pulp wastewater from one to three years, and analyzed for the
      distributing characteristics of organic chlorine in soils. The results showed
      that measured equilibrium isotherms for absorbable organic chlorine (AOCl) in the
      soils were of Freundlich type with the adsorption constant 7.3410 in the soils
      without irrigated and 4.9501 irrigated for 2 years. The nonlinear constants were
      0.5024 and 0.6108, respectively. The AOCl was detected in the leachate, it was
      found that most of the AOCl was adsorbed by the soils, especially topsoil. The
      average contents of extractable organic chlorine (EOCl) were 4.48 microg/g, 10.35
      microg/g and 10.07 microg/g in the topsoil irrigated for la, 2a and 3a
      respectively, which had increased distinctly compared with the background value.

PMID- 16881315
TI  - [Oxidation of pentachlorophenol by manganese dioxide].
AB  - This study examined the oxidative transformation kinetics of pentachlorophenol
      (PCP) by manganese dioxide (MnO2) at pH 4.12 solution using manganese dioxide as
      an oxidant. This study also discussed the influence of pH on the reaction
      kinetics. Results show that PCP has highly susceptible to oxidation by manganese
      dioxide. The loss of PCP slows as the reaction progresses and deviates from the
      simple pseudo-first-order kinetics but follows complex reaction kinetics when
      experiments were performed at a constant pH and with an enough excess of MnO2.
      Furthermore, the reaction rate of PCP decreases significantly as the pH of the
      reaction mixture increases from 3.5 to 6.6. Using solvent extraction and GC-MS
      analysis, one minor and two major products were detected. The minor product is
      the mixture of tetrachloro-1, 4-hydroquinone and tetrachlorocatechol, and the two
      major products are dimeric products that formed by coupling of pentachlorophenoxy
      radicals. Furthermore, the two major products are structural isomers, resembling
      each other except for the position of nine chloride atoms on the aromatic ring.
      On the basis of the surface reaction kinetics and product identification observed
      in this study, the reaction scheme for PCP oxidation by manganese dioxide is
      tentatively

PMID- 16881316
TI  - [Effect of application of silicon on arsenic uptake by rice seedlings in soil].
AB  - The objective of study was to investigate effect of silicon on arsenic uptake by
      rice seedlings in two soils with different arsenic concentrations. The results
      show that the addition of silicon has little effect on shoot and root dry weights
      of rice seedlings. The addition of silicon did not affect shoot and root P
      concentrations of rice seedlings grown in low arsenic soil, but significantly
      increased shoot P concentrations on rice grown in high arsenic soil. Irrespective
      of the initial pH of K2SiO3 solution, the addition of silicon significantly
      decreased shoot and root As concentrations of rice seedlings compared with the
      control. For seedlings grown in low As-contaminated soil, As concentrations in
      shoot and root were reduced by 36%-59% and 15%-37% with the application of
      silicon, respectively. For seedlings grown in high As-contaminated soil, As
      concentrations in shoot and root were reduced by 42%-58% and 70%-82% with the
      application of silicon, respectively. These results are in agreement with our
      previous reports based on a solution culture experiment. Possible mechanisms of
      the effect of Si on As uptake was also discussed.

PMID- 16881318
TI  - [Concentration limitations of pathogenic microorganisms in reclaimed water].
AB  - Using the technique of microbial risk assessment, concentration limitations of
      pathogenic microorganisms for various reclaimed water uses are studied. The
      concentration limitations are: Escherichia coli 70 MPN/L, Salmonella 0.5 CFU/L,
      Shigella 0.1 CFU/100L, Hepatitis A virus 0.001 PFU/100L, Rotavirus 1.2 x 10(-3)
      PFU/100L, Poliovirus 0.07 PFU/100L, Coxsackie 0.04 PFU/100L, Echovirus 0.05
      PFU/100L, Cryptosporidium 0.1 oocysts/100 L, Giardia lamblia 0.03 cysts/100 L.

PMID- 16881317
TI  - [Effects of Cd2+ on seedling growth and phytohormone contents of Glycine max].
AB  - A laboratory incubation experiment was conducted to study the effects of
      different Cd2+ concentrations on seedling growth and phytohormone contents of
      Glycine max through determining some physiological and biochemical indexes. The
      results showed as follows: (1) Different Cd2+ concentrations inhibited the
      synthesis of indoleacetic acid (IAA) and gibberellins (GA3) in roots and
      stimulated the synthesis of zeatin (Z) and abscisic acid (ABA) not only in roots
      but also in aerial parts of Glycine Max. Cd2+ stimulated the synthesis of IAA and
      GA3 in aerial parts at lower concentrations, but inhibited the synthesis of IAA
      and GA3 at higher concentrations. (2) Cd2+ stress for 84h increased the root
      vitality and the contents of chlorophyll a and b, but no significant difference
      was found in carotinoid contents compared with the control. (3) Cd2+ stress
      decreased POD activities and MAD contents atlower concentrations and increased
      POD activities and MAD contents at higher concentrations. With increasing Cd2+
      concentrations, this increase became significant gradually. (4) Cd2+ stress with
      lower concentrations stimulated the physiological activity of Glycine max
      seedling in a short time. When Cd2+ concentration was 0.50 mg/L, the root
      vitality, IAA and GA3 contents of Glycine max were the highest, and POD activity
      was the lowest.

PMID- 16881319
TI  - [Effect factors for mercury accumulation to natural surface coatings and analysis
      its forms of occurrence].
AB  - In order to probe to the factors for mercury accumulation to natural surface
      coating, we study the concentration of mercury in Huangpu River surface coatings
      developed for different depth, different grown days and different seasons and
      analysis mercury forms of occurrence. The result show the organic matter in
      biofilm is much high (7.5%-14.5%). Growth time, depth and seasons are all
      important factors for mercury accumulation to surface coating. Illumination and
      temperature was stronger and the growth day was longer, The concentration of
      mercury in biofilm was higher. The mercury forms of occurrence in surface coating
      were mainly residual matter bound mercury (41.98%) and organic acids bound
      mercury (27.89%). The percentage of carbonate bound mercury (10.17%) and ion
      exchangeable mercury (5.33%) was little.

PMID- 16881320
TI  - [Comparison between biomimetic sampling technique using semipermeable membrane
      device and bioconcentration in caged fish for polycyclic aromatic hydrocarbons].
AB  - Semipermeable membrane device (SPMD) was recently accepted to estimate the time
      integrated concentrations of bioavailable hydrophobic organic compounds (HOCs) in
      a similar manner as lipophilic bioconcentration. However few field researches
      were carried out to verify the similarities of SPMD and fish in concentrating
      HOCs from water. In present work, SPMD and caged crucian carps (Carassius
      auratus) were deployed side-by-side at five sites in Meiliang Bay, Taihu Lake for
      32 days and concentrations of polycyclic aromatic hydrocarbons (PAHs) in SPMD and
      fish were analyzed. The results showed that the composition of PAHs and relative
      concentration of individual PAH in SPMD and fish were quite similar. There was
      significant correlation between bioconcentration factors (lg BCF) and device
      concentration factors (lg DCF) for concentrations of PAHs (p < 0.0001). However
      in a quantitative analysis, lipid-normalized concentrations of PAHs in SPMD and
      fish were similar, and the ratios of the concentrations of PAHs in fish and SPMD
      were ranged from 0.47 to 4.12. In summary, SPMD could be the surrogate to
      estimate PAHs levels in fish in fresh water lake.

PMID- 16881321
TI  - [Toxic effects of petroleum hydrocarbons and copper on polychaete Nereis
      diversicolor and on its antioxidant enzyme systems].
AB  - Under the condition of the laboratory simulation, the toxic effects of petroleum
      hydrocarbons and various concentrations of copper (Cu2+) on the polychaete Nereis
      diversicolor and on its antioxidant enzyme defense systems were examined. The
      results indicate that both petroleum hydrocarbons and CU2+ have high toxicity to
      the polychaete. After a 3-day exposure to petroleum hydrocarbons and Cu2+, the
      value of LD50 was 117.5 microL x L(-1) and 864.0 microg x L(-1), respectively.
      The activities of peroxidase (POD) and superoxide dismutase (SOD) were influenced
      significantly through a 5-day exposure to single pollution of Cu2+. The activity
      of POD was inhibited at first and then enhanced gradually; on the contrary, the
      activity of SOD showed a tendency of induction firstly and then inhibition. After
      exposed to petroleum hydrocarbons at the concentration of the value of LD50 for 5
      days, POD activity of the polychaete was not significantly induced, and the
      activity of SOD was lower than that of control. A 5-day exposure to the joint
      pollution of petroleum hydrocarbons and Cu2+ could bring out a decrease in the
      activities of POD and SOD firstly and then an increase. The changes in the
      activity of SOD can better reflect the toxic effects of pollutants on the
      polychaete.

PMID- 16881322
TI  - [In situ identification of ANAMMOX bacteria in freshwater sediments].
AB  - In situ identification of ANAMMOX bacteria was conducted using 16S rRNA approach
      for sediment samples from the Xinyi River in Jiangsu Province, China. 16S rRNA
      clone library including 6 clone sequences was constructed. The alignment of these
      sequences and treeing were conducted using ARB package. Results show that the
      sediment samples contained 16S rRNA genes closely related to the known ANAMMOX
      bacterium Candidatus "Brocadia anammoxidans" (similarity of 91%). They also
      contained 16S rRNA gene sequences from a new branch of Planctomycetes distantly
      related to the ANAMMOX sequence cluster. However, the microbiological
      characteristics of these Planctomycetes are to be studied in the future. The
      detection of ANAMMOX bacteria will lead to further research on ANAMMOX process in
      the remediation and restoration of freshwater aquatic ecosystems and new
      understanding of the nitrogen cycle.

PMID- 16881323
TI  - [Community of activated sludge based on different targeted sequence of 16S rDNA
      by denaturing gradient gel electrophoresis].
AB  - In order to realize effect of different sets of universal primers on the analysis
      of microbial community of activated sludge based on targeted sequence of 16S rDNA
      and employ effectively denaturing gradient gel electrophoresis (DGGE), activated
      sludge were obtained from the continuous stirred tank reactor (CSTR), 16S rDNA
      fragments were amplified with there primer sets (341f/534r, 968f/1401r and
      341f/926r), and the diversity and dynamics of microbial communities were
      investigated by DGGE. The results indicated that community diversity and dynamics
      was obviously different based different sets of universal primers by DGGE.
      Separated patterns of the targeted sequence of primer 341f/534r and 968f/1401r
      were better than of 341f/926r. The similarity of communities between S2 and S3
      was high in the DGGE profiles with primer 341f/534r and 341f/926r, the similarity
      of communities between S1 and S2 was high in the DGGE profiles with primer 968f/1
      401r, it demonstrated that the similarity and dynamics of communities was
      different each other based different sets of universal primers. In the DGGE
      profiles, bands and diversity from primer 341f/534r were most, bands and
      diversity from primer 341f/926r were least. Thereby, while activated sludge was
      analyzed by DGGE, primers 341f/534r and 968f/1401r were more effective than
      341f/926r.

PMID- 16881324
TI  - [Microbial community structure in different wastewater treatment processes
      characterized by single-strand-conformation polymorphism (SSCP) technique].
AB  - In order to investigate microbial community structures in different wastewater
      treatment processes and understand the relationship between the structures and
      the status of processes, the microbial community diversity, variety and
      distribution in five wastewater treatment processes were studied by a culture
      independent genetic fingerprinting technique single-strand-conformation
      polymorphism (SSCP). The five processes included a denitrification and phosphorus
      removal bioreactor (N), Chinese traditional medicine wastewater treatment
      bioreactor (P), beer wastewater treatment bioreactor (W), fermentative
      biohydrogen production bioreactor (H) and sulfate-reduction bioreactor (S). The
      results indicate that the microbial community profiles in the same wastewater
      bioreactors are very similar. The diversity of microbial populations is
      correlated with the complexity of organic contaminants in wastewater. Chinese
      traditional medicine wastewater contains more complex organic components, so the
      population diversity is higher than that of simple nutrient bioreactors fed with
      molasses wastewater. Compared with the strain bands in a simulated community, the
      relative proportion of some functional microbial populations in bioreactors was
      not dominant, namely, fermentative biohydrogen producer Ethanologenbacterium sp.
      in the better condition bioreactor had only 5% band density, and the
      Desulfovibrio sp. in the sulfate-reducing bioreactor had less than 1.5% band
      density. SSCP profiles can define the difference in microbial community
      structures in wastewater treatment processes and monitor some of the functional
      microbes in these processes, providing useful guidance for improving its
      efficiency.

PMID- 16881325
TI  - [Enhanced ammonia removal and microbial community structure analysis using
      bacterial quinone profile in ITFB].
AB  - Water quality during the start-up period was changed in order to enhance the
      later nitrifying ability of the internal-circulation three-phase bio-fluidized
      bed (ITFB). The experimental results showed that high N/C ratio and low feeding
      concentration of COD were two key conditions for enhancing the ammonia removal.
      After the enhanced start-up, an efficient removal efficiency of both COD and
      ammonia was achieved with HRT 2h when treating sanitary wastewater, the average
      ammonia removal rate was 74% , the ammonia concentration in effluent was lower
      than 10 mg/L. Bacterial quinone profile of the system was also analyzed. The
      results showed that after the enhanced start-up, the number of nitrifying
      bacteria, such as Nitrosomonas europaea, in the biofilm in ITFB was increased,
      and the number of gamma-Proteobacteria, such as Acinetobacter sp. and Pseudomonas
      sp., was decreased. the equitability of the quinones (EQ) fluctuated around 0.5
      showed that the distribution of the microbial community in the biofilm changed
      little. UQ/MK ratio of all the samples was greater than 1 indicated that Gram
      negative bacteria was the dominant bacteria in the system.

PMID- 16881326
TI  - [Characteristics of atrazine-degrading genetically engineered microorganism (GEM)
      labeled with green fluorescent protein (GFP)].
AB  - The atrazine-degrading genetically engineered microorganism (GEM) was labeled by
      transforming a plasmid containing green fluorescent protein (GFP) gene. GFP gene
      could be expressed well in the cell of GEM after transforming. In the LB medium
      containing antibiotic, the expressing level of GFP was higher than in pure LB
      medium and in the basic medium. In the stable phase containing antibiotic, the
      expressing level of GFP was higher than in pure LB medium and in the basic
      medium. In the stable phase of cell growth, the expressing level of GFP was
      higher than in the lag phase and in the logarithmic phase. The transformation and
      expression of GFP gene wouldn't affect the degrading ability of GEM. The level of
      GFP expression was almost linear with the degrading activity. There exist two
      states of cells after inoculating GEM labeled with GFP into activated sludge:
      suspended state and adhered state to sludge floc, and the amount of suspended
      cells is higher than that adhered to sludge floc.

PMID- 16881327
TI  - [Culture medium and grading culture technics for bioflocculant production by
      Paenibacillus polymyxa GA1].
AB  - A bacterial strain named GA1 which can produce bioflocculant with high
      flocculating activity was isolated from soil. The strain was identified as
      Paenibacillus polymyxa according to its morphological, physiological and
      biochemical characters, as well as 16S rDNA sequence (GenBank Accession number:
      DQ166375) similarity comparison. The results indicated that sucrose and yeast
      extract were the optimal carbon and nitrogen sources for bioflocculant
      production. Furthermore, the mass ratio of sucrose to yeast extract and the
      optimal sucrose concentration were ascertained. The optimum component proportion
      of medium (g/L) is sucrose 40.0, yeast extract 4.0, K2HPO4 5.0, KH2PO4 2.0, NaCl
      0.1, MgSO4 0.2. The culture conditions including initial pH, temperature,
      agitation rate and inoculation quantity of strain GA1 were ascertained. Based on
      the relation of bacterium growth and bioflocculant production, grading culture
      was applied to bioflocculant production of GA1. The experimental result show that
      grading culture can keep high bioflocculant yield as well as shorten time of
      flocculant production.

PMID- 16881329
TI  - [Effect of temperature on bioleaching of Cr from tannery sludge].
AB  - Bioleaching processes are normally sensitive to temperature fluctuations. Shake
      flask experiments were conducted to examine these effects in the temperature
      range of 12-36 degrees C. The results showed that there was an increase in the
      rates of pH reduction and Cr solubilization efficiency with the increase of the
      temperature of bioleaching reaction. After 8 days of bacterial leaching
      treatment, almost 100% of Cr could be leached from tannery sludge at the
      temperature of 28 degrees C and 36 degrees C. The temperature of 28 degrees C is
      recommended to be employed in the future realistic operation.

PMID- 16881328
TI  - [Bioconversion of sewage sludge to biopesticide by Bacillus thuringiensis].
AB  - Feasibility of bioconversion of sewage sludge to biopesticide by Bacillus
      thuringiensis was studied using sewage sludge as a raw material. The fermentation
      was also compared with conventional medium. Results showed that without any
      pretreatment, the nutrients contained in sewage sludge were almost sufficient for
      Bacillus thuringiensis growth, even with a rapid multiplicational rate. Higher
      viable cells and viable spores values were obtained earlier at 24 h, with 9.48 x
      10(8) CFU x mL(-1) and 8.51 x 10(8) CFU x mL(-1) respectively, which was 12 hours
      earlier and nearly 20 percent higher than conventional medium. SEM of 36 h
      samples gave a clear phenomenon that the metabolizability in sludge was much
      faster with spores and crystals spreading around. The crystals in sludge seemed
      rather bigger and more regular. Also a better crystal protein yield of 2.80 mg x
      mL(-1) was observed in sludge medium compared to conventional medium at the end
      of fermentation. Sludge fermentation for Bacillus thuringiensis reduces the
      producing cost, and gives better fermentation capabilities. It's expected to be a
      new method for sludge disposal.

PMID- 16881330
TI  - [Co-digestion of waste activated sludge and kitchen garbage].
AB  - The effects of mixture ratio and hydraulic retention time on mesophilic co
      digestion of waste activated sludge and kitchen garbage were investigated, and
      the mixtures having the ratios of 75%:25%, 50%:50% and 25%:75% on a TS basis,
      operated at the HRTs of 10d, 15d and 20d. In all the digesters, with an OLR 1.53
      5.63 g/(L x d), there were no indication of failure, such as low pH, insufficient
      alkalinity, ammonia inhibition and accumulation of VFAs. The optimum operating
      conditions of all the digesters were found to be a mixture of 50%:50% in terms of
      the stability and performance, buffer capacity was the highest. The volatile
      solid removal efficiency, specific methane production and methane content in this
      condition achieved 51.1%-56.4%, 0.353-0.373 L/g and 61.8%-67.4%.

PMID- 16881331
TI  - [Using compost of agricultural solid waste to produce organic-inorganic compound
      fertilizer].
AB  - Techniques of compound fertilizer production from solid waste compost were
      studied. Different ratio of water moisture, proportion between organic and
      inorganic and infection of different granularity to the effect of granulation is
      separately determined through experiments at the pilot scale in the field. The
      optimal parameters of the techniques are determined. The moisture content is 35%
      40%; the rate of organic matter is 80%-90%; granularity is 20 mu. According the
      data of the organism's concentration, height and weight in crop, the crop was
      fertilized compound fertilizer is batter than chemical fertilizer. And the
      ability of increasing the production of the compound fertilizer was testified.

PMID- 16881332
TI  - [Detection carbamate pesticides residue in cucumber by immobilized
      acetyicholinesterase enzyme].
AB  - A novel method was described for detection carbamate pesticides residue in
      cucumber by immobilizing acetylcholinesterase enzyme in a micro-screen plate with
      96 wells based on GA-BSA-gelatin gels. The concentrations of BSA, GA and gelatin
      in enzyme immobilization solution were optimized and the best concentrations were
      5%, 0.5% and 0.1%, respectively. To analyze the pesticides residue 5g cucumber
      sample was homogenized with 10 mL acetone then an aliquot of 5mL extract was
      collected in a 10 mL test tube with a cap, into which 2g sodium chloride and 2mL
      dichloromethane were added in sequence. After shaking, 1 mL of the supernatant
      aliquot was evaporated by a blower in a small beaker and dissolved by 20%
      methanol-water solution then 50 microL was piped to a sample well. After
      incubation 10 minutes the absorbance was detected. The proposed method offered a
      rapid, simple and inexpensive means to in screen of batch samples. The minimum
      detection limit of this method was in a range of 0.1-0.2 mg/kg for cucumber
      samples.

PMID- 16881333
TI  - Peritoneal dialysis penetration in the United States: march toward the fringes?

PMID- 16881334
TI  - The choice study.

PMID- 16881335
TI  - Worshipping at the altar of St. Cox: who adjusts the adjustments?

PMID- 16881336
TI  - Is peritoneal dialysis associated with increased cardiovascular morbidity and
      mortality?

PMID- 16881337
TI  - Peritoneal dialysis in large dialysis chains.

PMID- 16881338
TI  - T lymphocytes: the "cellular" arm of acquired immunity in the peritoneum.
AB  - T cells are an important part of the acquired immune response and target specific
      antigen with their T cell receptor. The peritoneum is a special milieu within
      which T cells react. We describe briefly the anatomy important for T cell
      function. T cell biology including antigen presentation, T cell activation, and
      the different T cell subpopulations are reviewed. We also define innate and
      acquired immunity and describe the role of polymorphonuclear cells and peritoneal
      mesothelial cells in the regulation of leukocyte population recruitment during
      peritonitis. We focus particularly on peritoneal lymphocytes and compare them to
      the regular lymphocyte populations in the circulation. We illustrate the role of
      PMCs in antigen presentation and discuss the changes of CD4+ helper T cell
      subtypes (Th1 and Th2) during peritoneal dialysis. The role of CD8+ cytotoxic T
      lymphocytes and their possible destructive role for the peritoneal membrane
      modified by advanced glycation end products are discussed. Polymorphonuclear
      cells play an important role in the regulation of inflammation and immunity. We
      describe their possible role in supporting T cells and particularly for
      generating memory CD8+ T cells by secretion of interleukin-15, a potent T cell
      growth factor. Light is shed on gamma8T cells, a special T cell population that
      is able to recognize antigens without the restriction of antigen presentation. We
      end our review with a description of regulatory T cells. This cell population is
      extremely important in preventing autoimmunity and in the regulation of acquired
      immunity.

PMID- 16881339
TI  - Overfill or ultrafiltration? We need to be clear.

PMID- 16881340
TI  - Barriers to utilization of chronic peritoneal dialysis in network #1, New
      England.
AB  - OBJECTIVE: The percentage of prevalent end-stage renal disease (ESRD) patients
      maintained on chronic peritoneal dialysis (CPD) therapy in the United States
      declined from 15% in 1991 to 8.1% in 2002. Previous studies indicate that
      nephrologists in the United States feel 32.6% of prevalent ESRD patients should
      be on CPD therapy. The present study was designed to better understand the
      reasons for the discrepancy in actual versus desired prevalence of CPD
      utilization. METHODS: The medical directors of all dialysis centers in New
      England were mailed a questionnaire about the nephrologists' opinions concerning
      the percentage of patients that should be maintained on CPD therapy, reasons that
      limited patients' selection of CPD as initial therapy, and concerns about the
      current status of CPD therapy. The nephrologists were also invited to free text
      any other comments or concerns. RESULTS: A total of 117 questionnaires were sent;
      59 (50.4%) were returned. These medical directors cared for a median of 10 (range
      1 - 100) patients on CPD therapy, meaning 15% of dialysis patients in New England
      are maintained on CPD therapy. The medical directors felt that 29% (range 10% -
      50%) of prevalent ESRD patients should be maintained on CPD therapy. The most
      common reasons cited by the nephrologists as barriers to CPD therapy included
      patient preference (54%), contraindications to performing CPD therapy (32%), poor
      social support (31%), significant comorbid disease (20%), late referrals and
      acute hospital starts (19%), problems with education re chronic kidney disease
      (12%), and problems with the structure and organization of CPD facilities (12%).
      These same medical directors stated that concerns about technique failure (25%),
      long-term viability of CPD therapy (25%), and mortality rates of CPD patients
      (17%) impacted on their use of CPD therapy as renal replacement therapy for
      patients with ESRD. CONCLUSION: Nephrologists in New England felt that 29% of
      prevalent ESRD patients should be maintained on CPD therapy, yet the actual
      incidence of CPD utilization in New England is 15%. A variety of factors were
      cited by the nephrologists as important reasons limiting CPD utilization. These
      nephrologists were also concerned about technique failure and long-term viability
      of CPD therapy. It is necessary that we look closely at each domain cited by the
      nephrologists if CPD therapy is to remain a viable option for patients with ESRD
      in the United States.

PMID- 16881341
TI  - What is the link between poor ultrafiltration and increased mortality in anuric
      patients on automated peritoneal dialysis? Analysis of data from EAPOS.
AB  - BACKGROUND: Primary analysis of the European Automated Peritoneal Dialysis
      Outcomes Study (EAPOS) found that patients with daily ultrafiltration (UF) below
      a predefined target of 750 mL at baseline experienced increased mortality and
      continuing low UF over 2 years. SETTING: Multicenter, prospective observational
      study of prevalent, functionally anuric patients on automated peritoneal dialysis
      (APD) treated to predefined standards. METHODS: Secondary data analysis to
      determine clinical covariates that might support a link between poor UF and
      outcome, including pattern of comorbidity, prescription, nutrition as determined
      by Subjective Global Assessment (SGA), membrane function, and blood pressure
      (BP). Ultrafiltration was treated as a categorical (comparing patients above and
      below target at baseline) and continuous dependent variable in univariate and
      multivariate regression. The relationship between BP and survival was also
      explored. RESULTS: Of 177 patients recruited from 28 centers across Europe, 43
      were below the UF target at baseline. Compared to those above target, there were
      no differences in the spread of comorbidity, type of APD prescription, SGA, BP,
      hemoglobin, HCO3, or parathyroid hormone, at baseline or at any later time. At
      baseline, plasma calcium and, at 12 months, plasma phosphate were lower in the
      low UF group. There was a weak positive correlation between baseline systolic or
      diastolic BP and UF, which remained on multivariate analysis but accounted for
      just 9% of the variability in BP. There was no clear relationship between
      baseline BP and survival, although, if anything, low BP was associated with
      earlier death. Poor UF was associated with lower mean dialysate glucose
      concentration during the first 4 months and with consistently worse membrane
      function. CONCLUSIONS: The increased mortality associated with poor UF is likely
      multifactorial and not easily explained by clear differences in comorbidity,
      nutritional state, or other indices of treatment at baseline. The lower plasma
      phosphate suggests a subsequent fall in appetite. Poor BP control is unlikely to
      be the explanation, and a link between lower BP, reduced UF, and earlier death is
      suggested. Failure to achieve adequate UF due to worse membrane function remains
      an important and potentially reversible or preventable cause.

PMID- 16881342
TI  - ASPD: A prospective study of adequacy in Asian patients on long term, small
      volume, continuous ambulatory peritoneal dialysis.
AB  - BACKGROUND: The impact of small solute clearance on patient survival in
      continuous ambulatory peritoneal dialysis (CAPD) is not yet solidified.
      Previously, we demonstrated that CAPD using small volume (6 L) daily exchanges
      provides adequate dialysis for most Asian patients. METHODS: We conducted a
      prospective, long-term observational study to determine the optimal dialysis
      adequacy that may provide better patient survival for Asian patients who receive
      small-volume CAPD. We recruited 294 patients. The initial CAPD regime was 3 x 2-L
      exchanges daily. The same regime was maintained unless there was significant loss
      of ultrafiltration or fluid retention despite the use of hypertonic dialysate.
      RESULTS: Median study period was 38.9 (range 5 - 76.5) months, with 81% and 27%
      of patients remaining in the study at 24 and 48 months respectively. The overall
      survival rates at 2 and 4 years were 94.0% and 74.8% respectively. Our long-term
      data revealed that survival rate was related to Kt/V values. Survival rates were
      significantly higher for patients with total Kt/V > 2.0 than for patients with
      Kt/V < 1.7 (p = 0.02). The former group had lower body mass index and higher
      residual renal function and peritoneal Kt/V than the Latter group. On analysis
      using Cox proportional hazards regression models, cardiovascular disease (CVD),
      lower urine volume, and higher body mass index were independent predictors of
      mortality. Patients with higher renal Kt/V had a significantly lower risk of
      mortality (RR = 0.018, p = 0.01) after adjusting for the effects of CVD and
      diabetes mellitus. CONCLUSION: Our data recommend that 1.7 be the minimal target
      for total Kt/V in patients on long-term CAPD. Patients with high body mass index,
      low residual urine volume, and significant CVD need close monitoring.

PMID- 16881343
TI  - Modeling of icodextrin in PD Adequest 2.0.
AB  - OBJECTIVE: To validate the use of a modified three-pore model for predicting
      fluid transport during long dwell exchanges that use a 7.5% icodextrin solution.
      DESIGN: A nonrandomized, single group, repeated measures study. PATIENTS: Ten
      peritoneal dialysis patients underwent a single 8-hour exchange of a 7.5%
      icodextrin solution. All patients were naive to icodextrin. MAIN OUTCOME
      MEASURES: A modified three-pore model was used to model solute and fluid
      transport during each 8-hour exchange. Concordance correlation coefficients were
      used to estimate the level of agreement between modeled and measured values of
      net ultrafiltration (UF) and intraperitoneal volume. METHODS: Each patient
      underwent a modified 8-hour standard peritoneal permeability analysis using a 2-L
      7.5% icodextrin exchange. Dextran 70 was added to the icodextrin solution as
      volume marker to estimate fluid transport kinetics. Transcapillary UF, fluid
      absorption, and intraperitoneal volumes were assessed via the volume marker at 0,
      5, 15, 30, 60, 120, 240, 300, 360, 420, and 480 minutes. RESULTS: There was
      strong agreement (concordance correlation = 0.9856) between net UF as measured by
      the volume marker data and net UF as modeled using the modified three-pore model
      implemented in PD Adequest (Baxter Healthcare, Deerfield, Illinois, USA).
      CONCLUSIONS: Net UF and intraperitoneal volumes for long dwell exchanges using a
      7.5% icodextrin solution can be accurately modeled with a modified three-pore
      model. Steady state icodextrin plasma levels are needed to accurately predict net
      UF for chronic users of icodextrin.

PMID- 16881344
TI  - Physiological properties of the peritoneum in an adult peritoneal dialysis
      population over a three-year period.
AB  - OBJECTIVES: To describe the physiological properties of the peritoneal membrane
      in adult patients treated with peritoneal dialysis (PD) and to analyze the
      effects of patient characteristics and time. DESIGN: Observational study.
      SETTING: Department of Nephrology at the Sahlgrenska University Hospital. METHOD:
      Peritoneal function was analyzed by the Personal Dialysis Capacity (PDC) test,
      based on the three-pore theory of capillary transport. The functional PDC
      variables are absorption, large-pore flow, and the area parameter (A0/deltax),
      which determines the diffusion of small solutes. The ultra-filtration (UF)
      coefficient is determined mainly by A0/deltax. PATIENTS: All patients (n = 280)
      who had at least one PDC test done between September 1990 and August 1999.
      RESULTS: In 249 patients examined soon after start of PD, area was 19000 (SD
      7100) cm2/cm/1.73 m2, large-pore flow 0.112 (SD 0.052) mL/min/1.73 m2, and the UF
      coefficient 0.071 (SD 0.032) mL/minute/mmHg/1.73 m2. Absorption was 1.54 (SD
      +2.64, -0.97) mL/min/1.73 m2. Large-pore flow was greater in patients with severe
      comorbidity than in patients with fewercomorbid conditions. Elderly patients had
      a lower UF coefficient than did younger patients (p < 0.05). Repeated PDC tests
      were performed in 208 patients during a mean observation time of 18.4 months.
      There was a slight increase in the slope of the area-versus-time curve of 54
      cm2/cm/1.73 m2 per month (approximately 10% after 3 years, p < 0.01); all other
      parameters remained constant. CONCLUSION: Patient characteristics have an impact
      on peritoneal performance already at the start of dialysis. Peritoneal function
      can remain essentially stable during medium long-term PD.

PMID- 16881346
TI  - Compatibility of insulin over 24 hours in standard and bicarbonate-based
      peritoneal dialysis solutions contained in bags made of different materials.
AB  - BACKGROUND: The purpose of this study was to evaluate potency changes in insulin
      in different solutions and bag materials used for peritoneal dialysis (PD). One
      of the PD solutions (Physioneal) tested is available in two different solution
      containers, PVC and Clear-Flex. Four insulin concentrations (4 IU/L, 10 IU/L, 20
      IU/L, and 40 IU/L) were evaluated. This range of concentrations was defined in
      accordance with standard medical practice. All PD solutions made by Baxter,
      Castlebar, Ireland. METHODS: Insulin determination was performed by immunoassay
      (ELISA). RESULTS: In Dianeal, more than 90% of the initial dose of insulin
      remained available up to 24 hours for all concentrations tested. In Physioneal,
      for the higher concentrations tested (10 IU/L, 20 IU/L, and 40 IU/L), more than
      90% of the initial dose of insulin remained available up to 6 hours, and more
      than 80% up to 24 hours. For the Lowest concentration of insulin tested in
      Physioneal (4 IU/L), more than 90% of the initial dose of insulin remained
      available up to 3 hours, and more than 70% up to 24 hours. Also for the lowest
      concentration of insulin, recovery correlated with the pH of the tested
      solutions. This effect became apparent over the storage time. CONCLUSIONS: The
      data show that insulin adsorption is less than 10% during the first 3 hours for
      every PD solution tested. Insulin recovery tends to be stable or to decrease
      slightly over time for the lower insulin concentrations tested. The results for
      insulin recovery show a correlation with insulin concentration and with pH for
      the lowest insulin dose tested. From a solution-container interaction
      perspective, Clear-Flex is an equivalent alternative to standard PVC material.

PMID- 16881345
TI  - How to avoid glucose degradation products in peritoneal dialysis fluids.
AB  - OBJECTIVE: The formation of glucose degradation products (GDPs) during
      sterilization of peritoneal dialysis fluids (PDFs) is one of the most important
      aspects of biocompatibility of glucose-containing PDFs. Producers of PDFs are
      thus trying to minimize the level of GDPs in their products. 3,4-Dideoxyglucosone
      3-ene (3,4-DGE) has been identified as the most bioreactive GDP in PDFs. It
      exists in a temperature-dependent equilibrium with a pool of 3-deoxyglucosone (3
      DG) and is a precursor in the irreversible formation of 5-hydroxymethyl
      furaldehyde (5-HMF). The aim of the present study was to investigate how to
      minimize GDPs in PDFs and how different manufacturers have succeeded in doing so.
      DESIGN: Glucose solutions at different pHs and concentrations were heat
      sterilized and 3-DG, 3,4-DGE, 5-HMF, formaldehyde, and acetaldehyde were
      analyzed. Conventional as well as biocompatible fluids from different
      manufacturers were analyzed in parallel for GDP concentrations. RESULTS: The
      concentrations of 3-DG and 3,4-DGE produced during heat sterilization decreased
      when pH was reduced to about 2. Concentration of 5-HMF decreased when pH was
      reduced to 2.6. After further decrease to a pH of 2.0, concentration of 5-HMF
      increased slightly, and below a pH of 2.0 it increased considerably, together
      with formaldehyde; 3-DG continued to drop and 3,4-DGE remained constant.
      Inhibition of cell growth was paralleled by 3,4-DGE concentration at pH 2.0 -
      6.0. A high glucose concentration lowered concentrations of 3,4-DGE and 3-DG at
      pH 5.5 and of 5-HMF at pH 1. At pH 2.2 and 3.2, glucose concentration had a minor
      effect on the formation of GDPs. All conventional PDFs contained high levels of
      3,4-DGE and 3-DG. Concentrations were considerably lower in the biocompatible
      fluids. However, the concentration of 5-H M F was slightly higher in all the
      biocompatible fluids. CONCLUSION: The best way to avoid reactive GDPs is to have
      a pH between 2.0 and 2.6 during sterilization. If pHs outside this range are
      used, it becomes more important to have high glucose concentration during the
      sterilization process. There are large variations in GDPs, both within and
      between biocompatible and conventionally manufactured PDFs.

PMID- 16881347
TI  - Overfill of peritoneal dialysis bags as a cause of underestimation of
      ultrafiltration failure.

PMID- 16881348
TI  - Topical treatment of peritoneal catheter-related exit-site granuloma with
      acetamidohexanoic acid combined with gentamicin.

PMID- 16881349
TI  - Modality choice among Aboriginal incident dialysis patients--influence of
      geographic location.

PMID- 16881350
TI  - Icodextrin with small and short dwell enhances ultrafiltration in peritoneal
      dialysis patients with severe overhydration.

PMID- 16881351
TI  - Successful reinstitution of peritoneal dialysis after gastric resection: a case
      report.

PMID- 16881352
TI  - CAPD peritonitis due to Brevundimonas vesicularis.

PMID- 16881353
TI  - "Broom straw peritonitis" secondary to Cedecea lapagei in a liver transplant
      recipient.

PMID- 16881354
TI  - Actinomyces peritonitis in a patient on continuous cycler peritoneal dialysis.

PMID- 16881355
TI  - [An antidestructive effect of leflunomide in early rheumatoid arthritis].
AB  - AIM: To study effects of leflunomide on inflammatory and destructive processes in
      patients with early rheumatoid arthritis (RA). MATERIAL AND METHODS: The trial
      included 33 patients (27 females and 6 males) with a significant diagnosis of RA
      (A CR criteria) aged 19 to 60 years and duration of the disease from 6 months to
      3 years (15.97 +/- 9.70 months). The activity of the inflammatory process and
      treatment efficacy were assessed by severity of the articular syndrome, duration
      of morning stiffness (DMS), pain and the disease activity (VAS), device
      examination, the disease activity by DAS28 indices, etc. The articular syndrome
      was assessed by the number of painful joints (NPJ), number of swollen joints
      (NSJ), etc. The functional status of the patient was evaluated by Keitel test,
      HAQ and hand grip. Calculations were made of erosive arthritis progression rate
      (EAPR) and joint fissure narrowing progression rate (FNPR). All the patients
      received leflunomide (100 mg/day for 3 days, then 20 mg/day). A 12-month course
      was finished by 14 patients, 4 patients were withdrawn because of side effects,
      the rest--by social causes. RESULTS: To the end of the trial leflunomide reduced
      NPJ by 84%, NSJ--by 95%, DMS--by 88%, articular pain by VAS--by 66%, the disease
      activity by VAS--by 70%. A positive trend in DAS28 criterium was observed (a
      significant suppression of RA activity after 1 month of therapy by 18%, after 4
      months--by 39%, after 6 months--by 43%, by the end of the treatment--by 48%). For
      the initial 6 months EAPR was 0.50 +/- 0.67, for the following 6 months it
      lowered to 0.37 +/- 1.00, while FNPR decreased to 1.14 +/- 1.26 vs. 1.31 +/- 2 58
      for initial 6 months. A positive change of the level of type 3 matrix
      metalloproteinase (a 20% and 16% by month 4 and to the end of the trial,
      respectively) was registered. CONCLUSION: A positive effect of leflunomide on RA
      inflammatory activity and progression rate of joint destruction was confirmed.

PMID- 16881356
TI  - [Pro- and antioxidant blood system in patients with rheumatoid arthritis and
      systemic lupus erythematosus].
AB  - AIM: To estimate the levels of prooxidants (malonic dialdehyde-MDA and nitric
      oxide-NO), Zn, activity of antioxidant enzymes (superoxide dismutase--SOD and
      glutathione peroxidase--GPO) in the blood of patients with rheumatoid arthritis
      (RA) and systemic lupus erythematosus (SLE). MATERIAL AND METHODS: Pro- and
      antioxidant system was assessed in 45 RA patients and 32 SLE patients by content
      of MDA estimated by reaction with thiobarbituric acid, NO (Boehringer Manheim
      kits, Germany), Zn (Unicam SP 190/191, Great Britain), activity of SOD and GPO
      (kits Ransod, Ransel; Randox, Great Britain). RA activity was evaluated by DAS
      index, SLE--by SLEDAI. RESULTS: MDA and NO concentrations were found elevated
      while SOD and GPO activity low in RA and SLE. The level of Zn was subnormal in
      RA. The activity of RA and SLE did not influence the above indices significantly.
      CONCLUSION: RA and SLE patients have high levels of prooxidants (MDA and NO)
      whereas their antioxidant enzymes (SOD and GPO) activity was low. This may
      promote oxidant stress.

PMID- 16881357
TI  - [Activity of genetically programmed cell death of lymphocytes in rheumatoid
      arthritis].
AB  - AIM: To study activity of genetically programmed cell death (PCD) of lymphocytes
      in patients with rheumatoid arthritis (RA). MATERIAL AND METHODS: Lymphocytes
      from 30 RA patients including 14 patients with RA history up to 2 years, and 12
      healthy donors were studied for activity of caspase 4, 6, 8 usingfluorescence and
      caspase substrates 30, 60, 120, 150 and 180 min after start of the reaction and
      number of 1-2-thread serration of DNA with fluorescence of two DNA-tropic stains-
      EtBr and 4,6-DAPY Correlation was also studied between lymphocyte activity and RA
      activity, x-ray stage, duration, level of TNF-alpha. The trend in PCD activity of
      lymphocytes in immunosuppressive therapy was analysed. RESULTS: The activity of
      lymphocytic caspases in RA patients was low compared to healthy donors. A
      negative correlation was found between RA activity and activity of caspase 8 and
      6. In RA therapy with methotrexate, sulphasalasine, glucocorticosteroids the
      activity of caspases and number of 1-thread serrations of DNA were subnormal.
      CONCLUSION: RA is associated with lymphocyte PCD disorders which may be involved
      in RA pathogenesis, in formation of clones of potentially autoaggressive
      lymphocytes, in particular. This process is not normalized by current methods of
      RA treatment causing unsatisfactory outcomes of RA therapy.

PMID- 16881358
TI  - [Soluble receptors of TNF-alpha: association with atherosclerotic vascular
      affection in systemic lupus erythematosus in males].
AB  - AIM: To study association between concentration of soluble receptors of TNF-alpha
      (sTNFa-R1) and atherosclerotic vascular affection in systemic lupus erythematosus
      (SLE) in men. MATERIAL AND METHODS: The examination covered 75 patients (mean age
      34.76 +/- 11.8 years), duration of the disease 126 +/- 110 months. Standard
      cardiovascular risk factors were analysed. SLE activity was estimated by SLEDAI
      and ECLAM scales, SLICC/ACR index was calculated. Atherosclerotic vascular
      affection was studied with ultrasonic scanning of the carotid arteries. sTNFa-RI
      concentration in blood serum was determined with enzyme immunoassay technique in
      73 SLE patients and 20 healthy donors. RESULTS: By sTNFa-R1 concentration, the
      patients were divided into two groups. Group 1 consisted of patients with sTNFa
      R1 < or = 2.87 ng/ml, group 2 > 2.87 ng/ml. Higher concentrations of the
      receptors were associated with higher mean values of the damage index and
      proteinuria occurrence, with older age and higher body mass, with signs of
      vascular atherosclerotic affection (atherosclerotic plaques and intima-media
      thickness > 0.9 mm. CONCLUSION: Concentration of sTNFa-R1 can be considered as a
      laboratory marker of atherosclerotic vascular lesions.

PMID- 16881359
TI  - [The role of hyperhomocysteinemia in systemic lupus erythematosus and
      antiphospholipid syndrome].
AB  - AIM: To assess the role of hyperhomocysteinemia (HHC) in development of vascular
      complications in systemic lupus erythematosus (SLE) and antiphospholipid syndrome
      (APS). MATERIAL AND METHODS: A total of 125 participants (24 males and 101
      females aged 38 +/- 13 years) were divided into three groups: group 1--SLE
      patients (n=51); group 2--SLE+APS patients (n=49); group 3--primary APS patients
      (n=25). The patients had the disease for 14 +/- 11 years. Lupus anticoagulant
      (LA) and anticardiolipin antibodies (aCL) marked APS serologically. Homocystein
      (HC) was assayed by high performance liquid chromatography. HHC (HC > 15 mcg/l)
      was diagnosed in 82 of 125 (66%) patients: in 59% patients of group 1, 67%--of
      group 2 and 76%--of group 3. There was a relationship between HHC and digital
      necrosis (DN): 80% of DN patients had HHC while HHC was diagnosed in 57% patients
      free of DN (chi-square = 4.76, p = 0.03). Development of occlusions in APS was
      associated with HHC. Elevated levels of HC in blood was registered in 43 of 55
      (78%) APS patients with thromboses vs. 9 of 19 (47%) patients with APS free of
      thromboses (p = 0.03). HHC occurred significantly more frequently in patients
      with arterial thromboses (in all 14 patients) than in patients with venous
      thromboses (in 16 of 23--69.6%, p = 0.03) and in the absence of thromboses (in 9
      of 19, 47.4%, p = 0.04). HHC was associated with thromboses of cerebral,
      peripheral arteries (90 vs. 47% in patients without thrombosis, p = 0.005; 84 vs.
      47%, p = 0.04, respectively), coronary vessels (79 vs. 47%, p = 0.04). In APS
      patients having arterial thromboses with duration of postthrombocytic period
      (PTP), estimated as time from thrombosis to entering the trial, less than 2
      months, HC concentration was significantly higher (22.9 +/- 7.0 mcg/l) compared
      to patients with PTP more than 2 years (16.6 +/- 3.7 mcg/l (p = 0.04).
      CONCLUSION: More than 50% patients with SLE and APS, irrespective of APS
      variants, had an elevated HC level in the blood. Correlation between HHC and
      development of thromboses, primarily arterial, in APS gives grounds for the role
      of HHC in development of vascular complications in SLE and APS.

PMID- 16881360
TI  - [Clinical associations of C-reactive protein in systemic sclerosis].
AB  - AIM: To evaluate incidence of C-reactive protein (CRP) rise and CRP associations
      with clinical manifestations in systemic sclerosis (SS). MATERIAL AND METHODS:
      CRP concentrations in blood serum were estimated with solid phase enzyme
      immunoassay in 21 SS patients (8 patients with diffuse SS--dSS and 13 patients
      with limited SS--lSS). Two patients with ISS had documented rheumatoid arthritis
      (RA)--SS/RA. Forty two healthy donors with normal levels of CRP served control.
      RESULTS: CRP was elevated in 10 (48%) of 21 SS patients. Mean CRP content was
      9.87 +/- 7.73 mg/l (about 3 times higher than in the control group, p < 0.0001)
      in 20 eligible patients. A mean CRP level did not differ between ISS and dSS
      patients. RA patients had higher levels of CRP (p = 0.001). CRP was elevated in 4
      of 5 (80%) patients with digital ulcers and only in 5 (27%) of 15 patients
      without ulcers, but the difference was insignificant as well as those in mean CRP
      in these subgroups. Content of von Willebrand factor antigen (Ag:vW) was high in
      7 (33%) patients (mean 1.70 +/- 0.84 IU/ml) this being significantly higher than
      in the control group (p < 0.0001). CPR concentration closely correlated with that
      of Ag:vW (r = 0.52; p = 0.017). Close association was found between CRP level and
      ESR (r = 0.75; p < 0.001) and titer of antinuclear factor (r = 0.52; p = 0.035).
      CONCLUSION: A moderate rise of CRP level in about 50% cases of SS is associated
      with arthritis and cutaneous ulcers. A positive correlation between CRP content
      and Ag:vW in blood suggests that CPB concentrations may reflect severity of
      vascular damage in SS.

PMID- 16881361
TI  - [Soluble CD40 ligand in systemic lupus erythematosus and antiphospholipid
      syndrome].
AB  - AIM: To investigate a clinical role of soluble (s) CD40 ligand in systemic lupus
      erythematosus (SLE) and antiphospholipid syndrome (APS). MATERIAL AND METHODS: A
      serum concentration of sCD40 ligand was measured with enzyme immunoassay (Bender
      Medsystems, Austria) in 21 patients with primary antiphospholipid syndrome
      (PAPS), in 25 patients with secondary APS (SAPS) associated with SLE, in 92 SLE
      patients and in 16 healthy donors. RESULTS: A sCD40 ligand concentration in sera
      of SAPS and SLE patients was significantly higher than in donors. Significant
      differences by the ligand level between the above patients were not seen. In PAPS
      sCD40 ligand concentration was normal. Elevated serum concentration of the ligand
      was observed in 9.5% patients with PAPS, 54.0%--with SAPS, 73.9%--with SLE. This
      rise in SLE and SAPS was not related with the disease activity or renal damage.
      Hyperexpression of the ligand in APS was associated neither with thromboses nor
      with a high concentration of IgG/IgM antibodies to cardiolipin. A direct
      correlation occurred between sCD40 ligand level and platelet count. In SLE and
      SAPS elevation of the ligand level correlated with increased thickness of carotid
      artery intima-media complex, hypercholesterinemia and diastolic dysfunction of
      left ventricular myocardium. CONCLUSION: Hyperexpression of sCD40L in SLE and
      SAPS is associated with developing cardiovascular diseases and atherosclerosis.

PMID- 16881363
TI  - [Functional indices in assessment of gonarthrosis treatment efficacy with
      structum and chondrolon].
AB  - MATERIAL AND METHODS: The trial included 50 patients aged from 40 to 67 years
      with osteoarthrosis (OA) stage I and II by Kellgren-Lawrence. Patients of group 1
      (n=30) received chondrolon, of group 2 (n=20)--structum. Treatment efficacy was
      assessed by WOMAC scale, Leken's functional index, VAS pain at rest, walking,
      goniometry findings, time of 30 m walking. RESULTS: A positive clinical effect
      was achieved in both groups by all the indices. The improvement was significant
      in VAS pain, functional tests, Leken's index, WOMAC scale. A positive trend in
      clinical symptoms and tests developed more quickly in the treatment with
      chondrolon than with structum (in 8 vs. 12 months, respectively). Treatment with
      different chondroitin sulphate drugs raised quality of life in gonarthrosis
      patients assessed by WOMAC scale, the effect being comparable. CONCLUSION:
      Structum and chondrolon can be used for OA stage I-II with moderate dysfunction
      of knee joints. The treatment course should be long, at least 3 months, 3-6
      months for structum.

PMID- 16881362
TI  - [Metabolic syndrome and rheumatic diseases].
AB  - AIM: To characterize prevalence and features of rheumatic diseases in patients
      with metabolic syndrome, metabolic disturbances in patients with rheumatic
      diseases (RD), to ascertain their most frequent variants and characteristics.
      MATERIAL AND METHODS: After examination of 1291 therapeutic patients 19 to 79
      years of age for metabolic syndrome (MS), those with MS were screened for RD. In
      parallel, 1212 RD patients were studied for associated pathology: arterial
      hypertension, coronary heart disease, obesity, dyslipidemia, hyperuricemia and
      other components of MS. A separate electronic matrix was created for each of the
      two groups. Statistics were obtained using standard programs Statistica 6.0 and
      MS Excel 2000 for Windows XP 2000. RESULTS: MS was detected in 317 (24.6%)
      patients seeking medical advice (mean age 54.11 +/- 0.59 years). MS was complete
      in 272 (85.8%) patients, 287 (90.5%) had arthralgia, 131 (41.3%)--episodes of
      painful joints swelling in the presence of family history. RD were detected in
      295 (93.1%) MS patients. Osteoarthrosis, osteochondrosis and systemic
      osteoporosis occurred most often. Various metabolic disorders occurred in all the
      examinees with RD. The disorders were most pronounced in patients with gout and
      osteoarthrosis. CONCLUSION: MS patients comprise a group of a high risk for RD,
      especially gout and osteoarthrosis.

PMID- 16881364
TI  - [Comparison of quality of life and treatment efficacy in patients with chronic
      low back pain syndrome].
AB  - AIM: To test use of quality of life (QL) parameters for assessing treatment
      efficacy in patients with chronic low back pain syndrome (CLBPS). MATERIAL AND
      METHODS: Clinical, device examinations, questionnaire survey were made in 100
      patients, most of them females (77%) with CLBPS due to spinal osteochondrosis.
      Mean age of the patients was 45.69 +/- 7.61 years, mean duration of the disease
      10.20 +/- 6.01 years, duration of the exacerbation 4.04 +/- 1.75 months. Most of
      the examinees had CLBPS x-ray stage II. QL was evaluated by questionning (general
      SF-36, HAQ and special Oswestry low back pain disability (OLBPD) questionnaires).
      RESULTS: The patients were divided into two groups by clinical and device
      findings and responses to the questionnaires. Group I patients had significant
      improvement of all the parameters studied, patients of group 2 had no
      improvement. A strong correlation was found between OLBPD responses and the
      patients' appraisal of the treatment efficacy. The effect value, standardized
      significance rates and factors intensity reflected high informative value of the
      questionnaire by assessment of efficacy of CLBPS treatment. CONCLUSION: SF-36 and
      OLBPD are recommended as adequate general and special questionnaires
      respectively, to estimate QL in patients with CLBPS. The treatment is effective
      if total parameters of physical and mental health by SF-36 rise significantly
      while vital activity disorders by OLBPD reduce more than 2-fold.

PMID- 16881366
TI  - [Markers of inflammation--monocyte chemoattractant protein-1 (MCP-1) and C
      reactive protein--in blood of patients with unstable angina pectoris and stable
      effort angina].
AB  - AIM: To estimate concentrations of C-reactive protein (CRP) and MCP-1 in blood
      plasma of patients with unstable angina (UA) and stable effort angina (SEA).
      MATERIAL AND METHODS: Multiprojection coronaroangiography was performed in 12
      patients with UA and 11 patients with SEA. Hemodynamically significant stenosis
      (50% and more) at least in one major coronary artery was confirmed in all the
      patients. CRP and MCP-1 were measured with latex agglutination and enzyme
      immunoassay (Biosource kits), respectively. RESULTS: UA patients had
      significantly higher plasma levels of MCP-1 and CRP than those with SEA (107.25
      +/- 16.19 vs. 63.0 +/- 16.16 pg/ml and 1.99 +/- 1.64 vs 0.44 +/- 0.28 mcg/ml,
      respectively). CONCLUSION: Estimation of MCP-1, as a marker of vascular wall
      inflammation, can be used, in line with other indices, for verification of UA.

PMID- 16881365
TI  - [Catalytic autoantibodies as a new molecular instrument in rheumatological
      practice].
AB  - AIM: To compare clinicopathogenetic value of DNA-hydrolizing autoantibodies or
      DNA-abzymes in patients with systemic lupus erythematosus (SLE) and rheumatoid
      arthritis (RA). MATERIAL AND METHODS: We studied sera from 180 patients with SLE,
      180 RA patients and 128 healthy donors matched by age and gender; assessed
      catalytic and cytotoxic activity of DNA-abzymes in patients with different
      variants of SLE and RA course. RESULTS: The highest catalytic and cytotoxic
      activities of DNA abzymes were observed in SLE patients. In SLE catalytic and
      cytotoxic activities of DNA abzymes ranged widely and their mean values depended
      on SLE activity in patients with systemic lesions. DNA-abzymes in RA patients
      showed lower catalytic and cytotoxic activities in relation to substrate DNA and
      target cells than in SLE. DNA-abzymes occurred most frequently in patients with
      high activity of RA, slow-progressive and lingering course of RA, especially in
      early development of visceral (extra-articular) pathology. Characteristic for DNA
      abzymes in RA and SLE is the phenomenon of wide-range fluctuations due to factors
      determinating probability of induction of function of Ab-mediated catalysis and,
      therefore, incidence rates of DNA-abzymes, probably catalytic autoAb of the other
      specificity in a population of patients with systemic autoimmune diseases.
      CONCLUSION: The data indicate the validity of DNA abzymes use in clinical
      practice for realization of diagnostic and therapeutic programs in SLE and RA.

PMID- 16881367
TI  - [C677T mutation in methylentetrahydrofolatereductase gene in patients with venous
      thromboses from the central region of Russia correlates with a high risk of
      pulmonary artery thromboembolism].
AB  - AIM: To investigate genetic factors of risk (RF) to develop venous thrombosis and
      pulmonary artery thromboembolism (PATE) in population of central Russia. MATERIAL
      AND METHODS: We studied polymorphism of the genes of coagulation factor II
      (G20210A), factor V (G1691A) and methylentetrahydrofolatereductase (MTHFR) with
      polymerase chain reaction and restriction analysis of DNA amplified sites. We
      estimated prevalence of the mutations in healthy population and in patients with
      flebothrombosis as well as effects of the mutations on a PATE rate in patients
      with thrombosis. We examined 97 patients with documented flebothrombosis. PATE
      was detected in 54 of them. The control group consisted of 56 healthy volunteers
      matched by age and gender. RESULTS: G1691A mutation in the gene of coagulation
      factor V (Leiden mutation of factor V--LMFV) in healthy population occurred in
      3.6%, in patients with flebothromboses--in 19.6% (OR = 6.58; 95% CI from 1.47 to
      29.42; p = 0.006). Heterozygous mutation G20210A in prothrombine gene was
      detected in 8 (8.2%) patients (p = 0.027), while this mutation was registered in
      none controls. Polymorphism of MTHFR gene (C677T) was seen both in the control
      and patients (60.7 and 52.6%, respectively). LMFV occurrence in patients with
      flebothrombosis and PATE is less than in patients with flebothrombosis without
      TEPA (16.7 and 23%, respectively). The PATE risk is significantly higher in
      carriers of mutant allele 677CT and 677TT of MTHFR compared to patients free of
      this mutation (OR = 3.11; CI 95% from 1.35 to 7.15; p = 0.006). Homozygous
      inheritance of this mutation in males combined with PATE in 100% cases. Of 8
      carriers of heterozygous mutation G20210A in prothrombin gene PATE was detected
      in 5 carriers. CONCLUSION: LMFV and mutation G20210A in prothrombin gene are
      genetic risk factors of venous thrombosis. LMFV is not a PATE risk factor.
      Mutation C677T in MTHFR gene has no influence on the risk of venous thromboses
      but makes PATE much more probable. This suggests that it may be a genetic risk
      factor of PATE in this disease.

PMID- 16881369
TI  - [Diet therapy of rheumatoid arthritis].

PMID- 16881368
TI  - [Mechanisms of development of gout-related inflammation].

PMID- 16881370
TI  - [Allopurinol efficacy in patients with tophus gout and chronic renal failure].

PMID- 16881371
TI  - [A difficult way to diagnosis sarcoidosis].

PMID- 16881372
TI  - The threat of patients' desires...a matter of ethics.

PMID- 16881373
TI  - How we got from there to here and back.
AB  - Edward H. Angle dominated orthodontic armamentarium, diagnosis and treatment
      planning for almost a half century until Charles Tweed successfully challenged
      his mentor's nonextraction mantra. The ensuing diagnostic regimen used by Tweed,
      however, proved to have serious limnitations and clearly resulted in the
      extraction of too many teeth. This caused a subsequent deterioration of soft
      tissue appearances of patients that neither they nor their doctors liked. This
      article will describe and illustrate how new expansion techniques differ
      qualitatively from those of Angle, and how these techniques offer patients and
      doctors less invasive and more comfortable therapies which do not jeopardize
      facial appearances.

PMID- 16881374
TI  - Cranial strains and malocclusion: V. side-bend--part I.

PMID- 16881375
TI  - Introduction of a new orthodontic treatment planning software; a fuzzy logic
      expert system.
AB  - General practitioners can learn the mechanical aspects of orthodontics quickly.
      But they are not usually sure about the treament plans they propose. In this
      article, new software is described that proposes treatment plans fornon-surgical
      orthodontic cases. This computer program can receive patients' data in both
      graphical and numerical forms. The concepts of fuzzy logic have been used to
      enable the software to work with nominal parameters. This feature greatly
      simplifies the use of the software because it does not force the user to measure
      several numerical variables. Each patients' data is saved by this software and
      the saved data can be modified or deleted later. The computer program is prepared
      to deal with special cases such as incomplete dentitions appropriately. The
      software is supposed to reduce the number of inappropriate extractions and
      erroneous treatment plans for orthodontic purposes.

PMID- 16881376
TI  - The negative effect of mouth breathing on the body and development of the child.

PMID- 16881377
TI  - Parameters affect orthodontic treatment: part II.

PMID- 16881378
TI  - From orthotics to fixed orthodontics: phase 2 of TMJ therapy.

PMID- 16881379
TI  - Motivate your practice with recognition.

PMID- 16881380
TI  - The single unit transfusion in post partum hemorrhage: A new perspective.
AB  - Every year, about 210 million women become pregnant. Postpartum hemorrhage (PPH)
      is one of the major complications of pregnancy, accounting for 14 million cases
      annually. Of these, it is estimated that around 140,000 women die, resulting in a
      case fatality rate of 1%. PPH is defined by WHO as a blood loss > or = 500 mls.
      Most instances of PPH occur suddenly and without warning even in women without
      any of the known risks for this condition. If women do not receive timely medical
      treatment, as is often the case in many parts of the world, death can occur
      within two hours. The chance of receiving a safe blood transfusion as part of the
      therapy for PPH varies enormously from country to country, depending on whether a
      safe blood transfusion program has been set up as a part of the national health
      policy. The increasing realization of the potential deleterious effects of blood
      transfusion, including exposure to HIV and other viral agents, has changed the
      practices that were previously acceptable for the transfusion of blood, as has
      the recent recognition of specific patients who will benefit from a single unit
      of blood. In countries with limited resources, where a majority of women have
      anemia at the onset of their pregnancies, the slightest deviation from normality
      during labor and/or delivery leading to excessive hemorrhage can put a women's
      life at risk. In these instances, the patient needs urgent resuscitation,
      stabilization and transfer to a nearby center. Available blood, preferably typed
      cross matched and screened for infections, should be given until the patient
      receives specific treatment. This is especially true in bled- out obstetrics
      patients, where one unit may make the difference between a near death state and
      the possibility of slow recovery and survival.

PMID- 16881381
TI  - A comparison of transdermal and oral HRT for menopausal symptom control.
AB  - BACKGROUND: To compare clinical efficacy, side effects and continuation rates
      using oral hormone therapy (HT), percutaneous gel, and transdermal patch.
      METHODS: Eighty-eight symptomatic menopausal women were allocated into 3 groups
      (oral, gel, patch); the patch group was further subdivided to be given either
      reservoir or matrix patch. After one year of follow up, symptomatic improvement,
      side effects and continuation rates were assessed and compared. Statistical
      analysis was performed using multiple analysis of variants and chi-square tests
      wherever appropriate, with p value < or = 0.05 considered significant. RESULTS:
      Percentage of patients showing complete relief from vasomotor symptoms at one
      year were 62%, 95%, and 100% among oral, gel, and patch groups, respectively.
      Similarly, above-mentioned percentages were 30%, 65%, and 68% for psychological
      disturbances; 64%, 100%, and 100% for genital symptoms; 40%, 90%, and 100% for
      urinary symptoms. Incidence of side effects, such as breakthrough bleeding [6
      (60%), 6 (71%), and 5 (66%) among oral, gel, and patch groups at 6 months] and
      mastodynia [5 (14%), 6 (20%), and 5 (18%)] was comparable among three groups.
      Skin intolerance was significantly higher (92% of patients) in the reservoir
      patch group compared to the matrix patch (22% of patients) and gel (10% of
      patients) at first month. Continuation rate for one year was comparable among
      oral, gel, and matrix patch: 81%, 83%, and 88%, respectively. However,
      continuation rate was 50% among reservoir patch group. CONCLUSION: Transdermal HT
      performed significantly better than oral HT in menopausal symptom control.
      Reservoir patch was unsuitable in tropical climate where matrix patch and gel
      performed better.

PMID- 16881382
TI  - Soft tissue composition, axial bone mineral density, and grip strength in
      postmenopausal Turkish women with early rheumatoid arthritis: Is lean body mass a
      predictor of bone mineral density in rheumatoid arthritis?
AB  - OBJECTIVE: To study bone mineral density and body composition in patients with
      early rheumatoid arthritis to determine the relationship of lean mass, fat mass
      and hand grip strength to bone mineral density. METHODS: Fifty-one female
      patients who fulfilled the American College of Rheumatology (ACR) for RA were
      recruited. Fifty-one (51) female RA patients, age matched female control subjects
      and 53 osteoporotic patients (WHO criteria) were included in the study. All
      subjects were at postmenopausal period. Early RA is defined as the disease
      duration <10 years. Whole body composition and BMD were estimated by DEXA
      (Norland XR-46). Hand grip strength was measured by JAMAR hand dynamometer. Body
      mass index (BMI) and anthropometric measures (skinfold thickness and waist-hip
      ratio) were also assessed. RESULTS: The mean age of patients and controls was
      55.4 +/- 9.5, 56.9 +/- 7.4, and 55.2 +/- 7.6, respectively. There was no
      statistically significant difference in age, BMI, and years since menopause
      between RA patients, OP patients, and controls (p < 0.05). Bone mineral density
      of lumbar and femoral neck regions, total bone mineral density, and bone mineral
      content in RA patients were significantly lower than in controls but not in
      osteoporotic patients. Lean body mass was also significantly lower in RA patients
      than controls but not in osteoporotic patients. However, hand grip strength was
      significantly lower in RA patients than in osteoporotic patients and controls (p
      < 0.05). Total lean mass was correlated with body mass index, waist-hip ratio,
      femoral neck BMD, and total bone mineral content, total BMD in RA patients (p <
      0.05). Grip strength was correlated with duration of disease (RA) and age
      negatively, and also correlated with total BMD in RA patients. CONCLUSION: These
      results indicate that lean mass was associated with BMD. To preserve BMD,
      maintaining or increasing lean mass would appear to be an appropriate strategy
      for avoiding hip fracture and its complications.

PMID- 16881383
TI  - Factors related to post-treatment chronic pain in breast cancer survivors: the
      interference of pain with life functions.
AB  - The frequency and the intensity of chronic pain, as well as the related factors,
      were assessed in a cohort of breast cancer patients. The life functions were also
      questioned in patients who have post-treatment chronic pain. The scope of this
      retrospective study was a cohort of surgically-treated breast cancer patients
      with unilateral early stage disease who were under regular follow-up. Patients
      were eligible if they completed their treatments at least 6 months before and
      were free of disease. Patients who had a previous history of chronic pain
      syndrome, chronic debilitating disease, psychiatric diagnosis, and other cancers
      were excluded. All data regarding their demographics and treatments were
      recorded. Chronic pain was defined as the pain at treatment-related regions for a
      duration of at least three months after completion of treatment. Turkish version
      of "Brief Pain Inventory (Short Form)" was given to the patients with chronic
      pain in order to assess their pain intensity and life functions. The factors
      related to chronic pain were compared between patients with and without chronic
      pain. Eighty-five eligible female patients were included in the study. Thirty
      nine (46%) patients declared that they had chronic pain. The mean VAS scale score
      was 4.1 +/- 2.4 cm in these patients. The mean age of patients with chronic pain
      (54.3 +/- 12.6 years) was significantly less than that of the ones without pain
      (60.4 +/- 13.6 years; p = 0.035). Radiotherapy was found to be significantly
      related to chronic pain (p=0.049; OR: 2.60; 95% CI 1.07-6.30). The VAS scores
      were 1.5 +/- 2.7 cm, 1.9 +/- 3.2 cm, 1.3 +/- 2.7 cm, 0.9 +/- 2.5 cm for general
      activity, mood, relations with other people, and sleep, respectively. Although
      almost half of the early stage breast cancer patients experienced post-treatment
      chronic pain, they rated the intensity of their pain as mild to moderate. Younger
      age and receiving radiotherapy were found to be significant contributing factors.
      The interference of post-treatment chronic pain with life functions was small.
      Overall, mood was found to be the most affected life function among all.

PMID- 16881384
TI  - Correlation of Kupperman's index with estrogen and androgen levels, according to
      weight and body fat distribution in postmenopausal women from Mexico City.
AB  - OBJECTIVES: To establish the differences in Kupperman's index (KI) and hormone
      levels according to weight and body fat distribution in postmenopausal women,
      since obesity and fat distribution affect hormone levels. MATERIAL AND METHODS:
      One hundred and twenty-five postmenopausal women were studied and divided
      according to body mass index (BMI) and waist-hip ratio (WHR): normal weight (BMI
      < or = 27), obesity (BMI > 27); lower-level body fat distribution (WHR < or =
      0.85) and upper-level body fat distribution (WHR >0.85). Afterwards four
      subgroups were created: (I) BMI < or = 27 and WHR < or = 0.85, (II) BMI < or = 27
      and WHR > 0.85, (III) BMI > 27 and WHR < or = 0.85, and (IV) BMI >27 and WHR >
      0.85. Climacteric symptoms were analyzed with Kupperman's index. Estrone,
      estradiol, testosterone, androstenedione, and dehydroepiandrosterone sulfate
      determinations were done by radioimmunoassay and verified by chemoluminescence.
      The androstenedione-estrone and testosterone-estradiol ratios were calculated.
      Statistical analysis was by Student's t test for independent samples, plus
      Pearson's correlation analysis. RESULTS: Average age was 53.0 +/- 6.5 years, time
      since menopause 74.2 +/- 64.3 months. When comparing those with lower-level body
      fat distribution and those with upper-level body fat distribution, the A levels
      were significantly lower (P < 0.04) in those with upper-level distribution.
      Kupperman's index was significantly lower in subgroup I when compared with
      subgroups III and IV. The androstenedione level was lower in subgroup IV compared
      with subgroup III. In the whole sample, there was a correlation of the WHR with
      testosterone (0.297, P < .004) and the testosterone-estradiol ratio (0.209, P <
      .04). CONCLUSION: It was shown that the testosterone-estradiol ratio has a better
      correlation with the symptoms, so it can be used to evaluate climacteric patients
      when they complain of menopausal symptoms.

PMID- 16881385
TI  - Retinopathy of prematurity: A refresher for obstetricians.
AB  - Advances in neonatal care improved the survival of many preterm infants, but also
      increased the incidence of retinopathy of prematurity (ROP). Numerous risk
      factors have been associated with the development of ROP, the most important of
      which are: low birth weight, early gestational age at delivery, and duration of
      oxygen therapy. Screening premature infants is a critical factor for any
      prevention and treatment protocol. The Retinopathy of Prematurity Subcommittee of
      the American Academy of Ophthalmology (AAO) and the American Association for
      Pediatric Ophthalmology and Strabismus (AAPOS) have developed guidelines that
      assist practicing physicians in managing children with ROP. A portion of these
      guidelines is particularly applicable to practicing obstetricians who, along with
      the pediatricians, are often the primary physicians for the affected families.
      The aim of this paper is to present a comprehensive overview of the epidemiology,
      etiology, manifestations, prevention, and management of ROP. In the last section,
      the authors present guidelines for practicing obstetricians that incorporate the
      most recent recommendations of ophthalmic and pediatric thought leaders.

PMID- 16881386
TI  - Molecular technologies in parasitology, with an emphasis on genomic approaches
      for investigating parasitic nematodes.
AB  - In the last years, there have been substantial and rapid technological advances
      in the areas of genomics and genetics. These advances provide unique
      opportunities for exploring parasite development and reproduction at the
      molecular level and offer prospects for developing novel methods for the
      diagnosis and control of parasitism. The present keynote address illustrates the
      importance and impact of 'targeted' genomic studies of parasites in the wake of
      this technological revolution.

PMID- 16881388
TI  - Damage due to parasites in Mediterranean teleosts.
AB  - Evaluation of damages by parasites in teleosts, even if underextimated in the
      past, is today one of the most used methods to understand the effective impact of
      a parasite on a certain ichtyc species. The damage caused by a parasite on the
      host could be classified into direct, with tissue changes, or indirect, with a
      decrease of the productive performances. Based on this, a preliminary difference
      could be traced distinguishing parasites that show a coevolution with their host
      species, characterized by a low damage, and those parasites that can occasionally
      infect new host species, showing a high degree of damage. In consideration of the
      damage, parasites can have different actions on the host: subtractive,
      irritative, mechanical, traumatic, toxic, dismetabolic, antigenic and foretic.
      Those parasites able to cause tissue changes must be furtherly classified
      considering the type of inflammation they evoke on tissues: ulcerous, catarral,
      haemorrhagic, necrotic and granulomatous. Some parasites are encysted in tissues
      without any host reaction. The fish response against parasite can be
      inflammatory, the most frequent, but also hyperplastic, metaplastic, neoplastic
      and immunitary. The paper goes through different tissue changes due to the main
      parasites of Mediterranean teleosts.

PMID- 16881387
TI  - Parasitic diseases of marine fish: epidemiological and sanitary considerations.
AB  - Over recent decades, parasitic diseases have been increasingly considered a
      sanitary and economic threat to Mediterranean aquaculture. In order to monitor
      the distribution of parasites in cultured marine fish from Italy and study their
      pathogenic effects on the host, a three-year survey based on parasitological and
      histopathological exams was carried out on 2141 subjects from eleven fish species
      and coming from different farming systems (extensive, intensive inland farms,
      inshore floating cages, offshore floating cages and submersible cages). A number
      of parasitic species was detected, mostly in European sea bass (Dicentrarchus
      labrax), gilthead sea bream (Sparus aurata), mullets (Chelon labrosus, Mugil
      cephalus, Liza ramada) and sharpsnout sea bream (Diplodus puntazzo), with
      distribution patterns and prevalence values varying in relation to the farming
      system, in-season period and size category. The epidemiology and pathological
      effects of the parasites found during the survey are discussed.

PMID- 16881389
TI  - Parasites as biological tags in population studies of demersal and pelagic fish
      species.
AB  - Among the different techniques applied in a holistic approach for fish stock
      identification, the use of parasites as "biological tags" is becoming
      increasingly important. In this presentation, our recent studies on the use of
      some parasite species, identified by genetic markers, and the parasite/fauna
      composition, in stock identification of demersal (Merluccius merluccius), small
      pelagic (Trachurus trachurus), and large pelagic fish species (Xiphias gladius)
      are reviewed. Different species of Anisakis and Hysterothylacium were genetically
      identified by the application of genetic (allozyme) markers. Statistically
      significant differences in the spatial distribution of distinct species of
      Anisakis were found in the fish considered. As to the species of Hysterothylacium
      genetically detected, different relative proportions were detected in several
      Mediterranean and Atlantic samples of swordfish (X. gladius). This study
      demonstrates the potential value of these anisakid nematodes, at both larval and
      adult stages, as "biological tags" for these fish species in European waters.

PMID- 16881390
TI  - Myxozoan infections in Mediterranean mariculture.
AB  - Fish mariculture has dramatically expanded in recent years in Mediterranean
      countries. In this scenario, several pathological problems have logically arisen
      and parasitological etiologies are increasingly being reported, either as primary
      or secondary pathogens. Myxozoa is the most diverse and economically important
      group of fish parasites, and several species are known to cause or contribute to
      losses in mariculture. Species of the genus Enteromyxum currently constitute the
      most serious parasitological threat. Some unusual biological characters, such as
      wide host spectrum and direct fish-to-fish transmission, together with high
      virulence for some host species, combine a dangerous cocktail which is emerging
      in recent years. Closed-system (recirculation) and heated-water locations are
      especially sensitive to chronic infections by these parasites, which can cause
      serious mortality and even discourage culture of some fish species at certain
      locations (i.e, Diplodus puntazzo). The presentation presents an overview of
      recent advances in research of marine myxozoans, focusing mainly in the most
      pathogenic, Enteromyxum spp. The incidence of these and other emerging
      infections, and the design of potential strategies for control will be
      introduced.

PMID- 16881391
TI  - Dynamics of parasite communities and interactions between wild and domestic
      ruminants.
AB  - Dynamics of parasite communities and host-parasite-environment interactions can
      be influenced by different factors. The present note, by discussing some field
      experiences in wild and domestic ruminant populations, approaches eco
      epidemiology of abomasal nematodes in relation with host health and dynamics.
      Factors possibly playing a role in the host-parasite relationship are discussed,
      as well as possible use of macroparasites as ecological and sanitary indicators.
      The above topics are approached in a management perspective, in particular
      regarding interactions between domestic and wild ruminant populations.

PMID- 16881392
TI  - Ecology and epidemiology of Echinococcus multilocularis in Europe.
AB  - Human alveolar echinococcosis (AE), caused by the larval stage of Echinococcus
      multilocularis has a high mortality rate in untreated patients. The life-cycle of
      E. multilocularis in Europe predominantly involves foxes as definitive hosts.
      However, experimental studies demonstrated a comparable biotic potential of E.
      multilocularis in dogs and raccoon dogs but an insignificant potential in cats.
      AE occurs in central and eastern Europe at low incidence rates. Recent studies in
      foxes have shown that E. multilocularis has a wider geographic range (including
      Italy) than previously thought. In recent years, increases in fox populations
      have been observed in many European countries, especially in urban areas. As a
      result, the E. multilocularis cycle is now established in the urban environment.
      This presents an increased risk of infection for a large human population. Based
      on these facts and new epidemiological data, possible intervention strategies are
      presented.

PMID- 16881393
TI  - The ecology of the parasite population in micro-mammals in the Italian peninsula
      and islands.
AB  - The importance of micro mammals from many points of view, mainly with an
      ecological approach was stressed. The study of the spatial-temporal distribution
      of parasites in their hosts may be carried out in several ways. Tests done in
      collaboration with the Parasitology Laboratory in the Faculty of Chemistry at the
      University of Barcelona, the NRCS and the Department of Ecological Studies in
      Cosenza, have contributed to an understanding of the Helminth communities as
      relating to several intrinsic variables of microteriofauna as well as extrinsic
      ones, particularly those concerning environment, climate and season. These
      comparisons were made using statistical means which compared the categorical and
      dichotomic variables which would highlight risk differences and their effects on
      the system. Quantitative dependent variables were also considered in relation to
      the aforementioned qualitative variables. One of the models studied is that of
      logistic regression, which estimates the function of regression, connecting the
      probability of the presence of Helminth as a dependent variable, with biological
      and ecological parameters (independent variables) such as: gender, age, season of
      capture, bioclimate, biotope and trapping section.

PMID- 16881394
TI  - Echinococcus multilocularis in north Italy.
AB  - Alveolar echinococcosis is a zoonotic infection caused by the metacestode of the
      tapeworm Echinococcus multilocularis. Fox populations living in the Alpine
      regions of Italy had been considered free from this parasite until 2002, when two
      infected foxes were detected in Bolzano province (Trentino Alto Adige region)
      near Austrian border. A modified nested PCR analysis was used to detect E.
      multilocularis DNA in faecal samples belonging to red fox populations from five
      Italian regions. A total of 522 faecal samples were analysed from foxes shot in
      Valle d'Aosta (N = 65), Liguria (N = 44), Lombardy (N = 105), Veneto (N = 67),
      and Trentino Alto Adige (N = 241) regions. Among these, 24 samples, all from the
      Trentino Alto Adige region, were found positive. Moreoever, 1406 faecal samples
      of red foxes were analyzed by CA-ELISAs commercial test kit. This paper provides
      an update of the epidemiological knowledge of this parasite in north Italy.

PMID- 16881395
TI  - Models of parasite biocoenosis dynamic: host density and gastrointestinal
      parasites in alpine chamois.
AB  - Host density is an important and widely accepted factor influencing
      microparasites epidemiology. In theory, host density would influence also
      macroparasite dynamic, although it would be achieved indirectly due to the
      presence of free-living infective stages of parasites. On this basis, it is
      expected that macroparasite abundance and prevalence would increase as host
      density increases, due to the higher probability for a new host to acquire
      infections from the environment. Nevertheless, some surveys indicate a negative
      relationship between host density and gastrointestinal helminth abundance in
      alpine chamois. On the basis of data collected from three different chamois
      populations, the Authors discuss the possibility that ecological factors
      different from host density should influence parasite biocoenosis dynamic,
      leading to the pattern observed in natural chamois-parasite systems.

PMID- 16881396
TI  - Human infections due to nematode helminths nowadays: epidemiology and diagnostic
      tools.
AB  - An update on the epidemiology of intestinal and tissue roundworms, in the world
      as well as in Italy, is presented. This analysis indicates that the most
      important changes happened in developed countries, where two main phenomena have
      been registered. The improvements occurred in social, economic, hygienic and
      sanitary conditions resulted in decrease of intestinal geohelminth prevalence
      but, besides, the changes happened at level of other factors, like environment,
      climate and human behaviour, promote more and more the opportunity for infections
      due to animal nematode species, which in people induce tissue syndromes.
      Therefore, the easier circulation of zoonoses among humans constitutes the main
      remark, which has to be strongly taken into account in countries like Italy, in
      that it is an emerging sanitary problem, important both for the number of people
      involved, and for the difficulties induced by their diagnosis. The general trend
      of "traditional" and "new" nematode infections that can affect humans is
      analysed, changes in the distribution patterns are tentatively explained, and
      available diagnostic tools are summarised.

PMID- 16881397
TI  - Updates on cystic echinococcosis (CE) in Italy.
AB  - An update on Cystic Echinococcosis (CE) diffusion in Italy during 2003-2005 is
      reported. CE seems to have a sporadic diffusion in the northern part of the
      country where this disease plays a minor role (prevalence < 1%). Recent
      investigations have shown the occurrence of CE cases in humans from the mountains
      between Reggio Emilia and Modena, with an average year incidence between 9.4 and
      5.6/100,000. In Abruzzo prevalences in sheep and cattle are 20.2% and 15.3%, with
      a fertility of 4.6% and 1.3%, respectively. In the same region, G1 and G3 strains
      were identified and a prevalence of 31% in dogs was found with CaELISA. In
      Campania, CE prevalence was 14.8% in cattle, with no viable cysts recovered, and
      10.5% in water buffaloes, with a fertility of 1.4%. Biotechnologies allowed to
      find G1 and G3 strains in water buffaloes. In Sicily, CE was found in 67.1% of
      cattle, with a fertility of 4%, and in 57.6% of sheep, with 9.2% of viable cysts.
      Biomolecular investigations have found G1 strain in sheep and cattle. In dogs, a
      prevalence of 5.6% for Echinococcus granulosus was reported. In Sardinia CE
      prevalence was 75.3% in sheep and 41.5% in cattle, with a fertility of 10.3% and
      2.6%, respectively. CE was found also in 9.4% of pigs, with fertility of 6.5%.
      The G1 strain was recovered in sheep and cattle while the G7 in pigs.

PMID- 16881398
TI  - Updates on morphobiology, epidemiology and molecular characterization of
      coenurosis in sheep.
AB  - Taenia multiceps (Leske, 1780) is a taeniid cestode that in its adult stage lives
      in the small intestine of dogs and other canids. The metacestode, previously
      known as Coenurus cerebralis, is usually found in the nervous system including
      brain and spinal cord in sheep and other ruminants. The presence of cysts
      typically leads to neurological symptoms that in the majority of cases result in
      the death of the animal from starvation after some weeks. Coenurosis could cause
      high losses in sheep farms because the disease affects young animals that the
      farmers grow up each year as replacements of the older individuals. Coenurosis is
      also a zoonosis with more than 100 human cases described in literature, of which
      the last in Italy and almost 5 reported in Sardinia. In the last years, the
      popularity of coenurosis has increased in sheep breedings because of the
      necessity to operate a differential diagnosis from another neurological disease,
      scrapie, particularly in atypical cases of coenurosis that could occur also in
      adult (2-3 years of age) sheep.

PMID- 16881399
TI  - Cystic echinococcosis: progress and limits in epidemiology and immunodiagnosis.
AB  - This study discusses the epidemiology and immunodiagnosis of cystic
      echinococcosis (caused by Echinococcus granulosus). Despite the development of
      molecular methods to prepare antigens, nowadays there is no standard, highly
      sensitive, and specific test available for antibody detection in cystic
      echinococcosis. Furthermore, because serological tests can give only a limited
      support to clinical findings there is a clear need for new advances in
      immunodiagnosis of E. granulosus infection.

PMID- 16881400
TI  - Downscaling climate information for local disease mapping.
AB  - The study of the impacts of climate on human health requires the
      interdisciplinary efforts of health professionals, climatologists, biologists,
      and social scientists to analyze the relationships among physical, biological,
      ecological, and social systems. As the disease dynamics respond to variations in
      regional and local climate, climate variability affects every region of the world
      and the diseases are not necessarily limited to specific regions, so that vectors
      may become endemic in other regions. Climate data at local level are thus
      essential to evaluate the dynamics of vector-borne disease through health-climate
      models and most of the times the climatological databases are not adequate.
      Climate data at high spatial resolution can be derived by statistical downscaling
      using historical observations but the method is limited by the availability of
      historical data at local level. Since the 90s', the statistical interpolation of
      climate data has been an important priority of the Agrometeorology Group of the
      Food and Agriculture Organization of the United Nations (FAO), as they are
      required for agricultural planning and operational activities at the local level.
      Since 1995, date of the first FAO spatial interpolation software for climate
      data, more advanced applications have been developed such as SEDI (Satellite
      Enhanced Data Interpolation) for the downscaling of climate data, LOCCLIM (Local
      Climate Estimator) and the NEW_LOCCLIM in collaboration with the Deutscher
      Wetterdienst (German Weather Service) to estimate climatic conditions at
      locations for which no observations are available. In parallel, an important
      effort has been made to improve the FAO climate database including at present
      more than 30,000 stations worldwide and expanding the database from developing
      countries coverage to global coverage.

PMID- 16881401
TI  - Statistical methods for geographical surveillance in veterinary epidemiology.
AB  - Spatial clustering and cluster detection are statistical analysis developed to
      address relevant scientific hypothesis. The difficulty stays in the large number
      of alternative hypothesis due to the different mechanisms that could generate the
      anomalous cases aggregation. We review methods for marked point data
      (case/control) aimed to describe spatial intensity of disease risk, to test for
      randomness and to locate significant excesses. Bayesian Gaussian Spatial
      Exponential models are used to illustrate probabilistic aspects and the link with
      simpler non parametric tools are shown. We develop an informal guideline to the
      analysis and used data on faecal contamination and dog parasitic diseases in the
      city of Naples, Italy. Kernel density estimation resulted very sensitive to
      bandwidth choice and overemphasized localized excess, Ripley'K function and
      Cuzick-Edwards test were very consistent each other while the SatScan failed to
      detect excesses. The spatial range was around 600 meters and justifies several
      small clusters. Bayesian models were very powerful in reconstructing the
      phenomenon and allow inference on model parameters in good agreement with the non
      parametric analysis.

PMID- 16881402
TI  - Biology-based mapping of vector-borne parasites by geographic information systems
      and remote sensing.
AB  - Application of growing degree day-water budget analysis and satellite climatology
      to vector-borne parasites will be reviewed to demonstrate the value of using the
      unique thermal-hydrological preferences and limits of tolerance of individual
      parasite-vector systems to define the environmental niche of disease agents in
      the landscape by modern geospatial analysis methods. Applications of geospatial
      modeling will be illustrated by examples on fascioliasis, malaria, leprosy and
      leishmaniasis.

PMID- 16881404
TI  - Disease mapping in veterinary parasitology: an update.
AB  - The development of methods for disease mapping has progressed considerably in
      recent years. Geographical Information Systems (GIS) and Remote Sensing (RS)
      represent new tools for the study of epidemiology, and their application to
      veterinary medicine, and in particular to veterinary parasitology, has become
      more and more advanced to study the spatial and temporal patterns of diseases.
      The present paper reports an update regarding the use of these technologies in
      veterinary parasitology.

PMID- 16881403
TI  - Agrometeorology and models for the parasite cycle forecast.
AB  - Insects are strongly influenced by meteorological variables in their natural
      environment. In agriculture, mathematical models have been developed to
      understand and forecast the cycle of pests based on climate data. By this manner,
      with the goal of reduce and rationalize plant chemical treatments,
      agrometeorological models have been realized to estimate the length and starting
      times of parasites phenological phases. In Sicily a new network of 95 GSM
      meteorological stations and a specific mathematical model for Aonidiella aurantii
      are used by Sicilian Agrometeorological Information System (SIAS) for the
      integrated pest management program of citrus orchards in the Island. As the
      plants parasites, vector borne diseases are influenced by climate in their
      appearance and abundance. In lights of the benefits that could derive from a
      model for the control of Leishmania vectors, SIAS experiences in modelling were
      used to develop a deductive model for Phlebotomus perniciosus which represents
      the major vector of human and canine leishmaniasis in Sicily.

PMID- 16881405
TI  - Waterborne transmission of Giardia and Cryptosporidium.
AB  - Giardia and Cryptosporidium spp. are parasitic protozoa which are frequent
      etiologic agents of waterborne diseases. This lecture will summarize the main
      biological and environmental factors involved in the potential risk for
      waterborne transmission of giardiosis and cryptosporidiosis, which have caused
      many outbreaks in different geographical areas. In particular, the current
      epidemiological situation of these parasitoses in Italy will be analysed, on the
      basis of research carried out on humans and on the environment. Finally, current
      methods for evaluating the presence of Giardia cysts and Cryptosporidium oocysts
      in water and new methods for cyst/oocyst removal from drinking water and
      wastewater will be examined.

PMID- 16881406
TI  - Giardia, Cryptosporidium and the spectre of zoonosis: the Italian experience from
      land to sea.
AB  - In the last decade, a major concern for the scientific community has been whether
      infected animals can serve as reservoirs of Giardia and Cryptosporidium infection
      for humans. Worldwide, prevalence studies and molecular tools have provided
      insights into the taxonomy and epidemiology of these protozoa in order to better
      understand such a relation. This paper presents data on the prevalence and
      molecular genotyping studies from several sample types from land to sea (humans,
      companion animals, sheep, cattle, goats, wastewaters, surface water, and
      shellfish) available in Italy. The contribution of Italian researchers to the
      international debate on the veterinary significance of these infections and their
      impact on public health is highlighted and the main objectives to be pursued in
      the future depicted.

PMID- 16881407
TI  - Zoonotic protozoa--food for thought.
AB  - Outbreaks of water- and foodborne diseases caused by Cryptosporidium, Giardia and
      Toxoplasma are well documented. Three features of these zoonotic protozoa ensure
      a high level of environmental contamination and enhance the likelihood of
      waterborne transmission. Firstly, they are responsible for disease in a broad
      range of hosts including man, have a low infectious dose enhancing the
      possibility of zoonotic transmission, secondly, their transmissive stages are
      small in size and environmentally robust and thirdly are insensitive to the
      disinfectants commonly used in the water industry. In addition, there is growing
      evidence for the role that water and food can play in the transmission of the
      microsporidia, Balantidium and Blastocystis to humans.

PMID- 16881408
TI  - Apicomplexa genes involved in the host cell invasion: the Cpa135 protein family.
AB  - The availability of a bulk of genomic data of Apicomplexa parasites is a unique
      opportunity to identify groups of related proteins that are characteristic of
      this phylum. The Cpa135 protein of Cryptosporidium parvum is expressed and
      secreted through the apical complex at the invasive stage of sporozoite. This
      protein is characterised by an LCCL domain, a common trait of various secreted
      proteins within Apicomplexa. Using the Cpa135 as a "virtual template", we have
      identified Cpa135 orthologous genes in four apicomplexan species (Plasmodium
      falciparum, Theileria parva, Toxoplasma gondii and Eimeria tenella). In addition,
      the architecture of the deduced proteins shows that the Cpa135-related proteins
      are a distinct family among the apicomplexan LCCL proteins.

PMID- 16881409
TI  - Proposal of Health Information System (HIS) as tool for the epidemiological
      surveillance of leishmaniasis in urban areas.
AB  - In recent years leishmaniasis has become a serious Public Health problem in
      Italy. The coexistence of infected dogs, vectors and humans, makes urban areas
      suitable environment for the spread of this zoonotic disease. With the purpose to
      improve the current system for the control of leishmaniasis in urban areas, the
      authors report their experiences carrying out a Health Information System (HIS)
      for the surveillance of the disease in the city of Messina. The HIS project is
      built on a dataset containing geographical data on urban environment, census
      tracts at parish level and data of human and canine leishmaniasis cases reported
      in the last years. The HIS allows the spatial representation of the disease
      occurrence and can be used as a novel epidemiological tool to perform area-based
      surveillance.

PMID- 16881410
TI  - Dogs' parasite and zoonotic risk: from old to new "emergencies" in the North-West
      of Italy.
AB  - Toxocariasis due to soil contamination from dog and cat faeces has been long
      described and represents one of the zoonotic risk linked with pets presence in
      human settlements. Soil samples were collected from private backyards and school
      playgrounds in Turin and tested for the presence of Toxocara spp. eggs. Samples
      from dogs and cats living in the same area were also analysed and our results
      seem to indicate a decrease in soil contamination respect to a survey carried out
      in 1985. Considering that recently new foci of Canine Leishmaniosis and the
      presence of competent sand fly vectors have also been reported in the North-West
      of Italy, a survey was carried out on dogs and humans living in Asti province. To
      assess the risk of local Leishmania infantum transmission between dog and humans,
      samples were also analysed by Restriction Fragment Length Polymorphism (PCR
      RFLP). Our results have shown that more than 10% of autochthonous dogs and human
      being living in this previously non-endemic area have been infected by L.
      infantum. The identity of PCR-RFLP patterns from 3 human clinical cases and from
      the dogs of one of them allows us to confirm the autochthonous origin of these
      cases.

PMID- 16881411
TI  - Urban faecal pollution and parasitic risk: the Italian skill.
AB  - Owing to the recent emergency of urban faecal pollution it is important to point
      out new strategies in order to fight the problem starting with the knowledge of
      past experiences. A punctual chronography of the different approach (telluric,
      coprological--zoonotic and phenomenological) was attempted to furnish a
      scientific base for future, modern approach.

PMID- 16881412
TI  - Mycetes and urban areas.
AB  - Mycetes are ubiquitous organisms that can cause mycoses in human and animals. The
      role of animals in the epidemiology of human mycoses in urban areas is multiform,
      but here will be discuss only two features: A) animals as vectors of mycoses and
      B) animal substrates as growth factor of pathogenic fungi. A) Animals as vectors
      of mycoses: this role is important as zoofilic dermatophytes are very important
      agents of zoonosis; the urban dermatophytozoonoses are prevalent caused by
      Microsporum canis which is prevalent in cats and dogs. Cats are often
      asymptomatic carriers. The pattern of human dermatomycoses has changed in Italy
      during the past century: at the beginning of the century anthropophilic fungi
      were prevalent while at present the zoophilic fungi are the most important
      causes. B) Animal substrata as growth factor of pathogenic fungi: soil
      "animalization" (i.e., the addition of such debris as hair, skin scales, dropping
      and other organic matters) creates an optimal substratum for the growth and the
      multiplication of geophilic or saprophyitic fungi, such as Microsporum gypseum
      and Cryptococcus neoformans. The present human lifestyle, which favours a an
      overpopulation of birds, wild animals, domestic mammals and sinanthropic together
      with man in crowded areas seems to favour the formation of environments adapted
      to the abundant growth of some pathogenic fungi with consequent infection for man
      and animals. Finally, an environment heavily populated by fungi can cause
      allergic pulmonary reactions as well as reactions in other organs and tissues.
      The control of human and animal fungi, and the efficient use of a monitoring
      system require ample knowledge of mycological problems both in human and
      veterinary medicine and of efficient laboratories capable of resolving the needs
      of both disciplines. Close collaboration between veterinarians, doctors and
      mycologists is necessary in order to resolve health problems linked to mycosis.

PMID- 16881413
TI  - Geographical Information Systems and canine faecal contamination: the experience
      in the city of Naples (southern Italy).
AB  - Geographical Information Systems (GIS) can be used to make transect sampling when
      non-moving objects are to be counted, involving choosing a line or series of
      lines along which the counts are to take place. This approach has been used by us
      in order to study canine faecal contamination in the city of Naples (southern
      Italy), and to evaluate the consequent presence of canine parasitic elements. A
      GIS was constructed utilizing the geo-referenced digital photographs and the
      cadastral maps of Naples. In order to uniformly evaluate the canine faecal
      contamination throughout the city, a grid representing sub-areas of 1 km x 700 m
      was overlaid on the city map within the GIS. The territory of Naples was divided
      in 218 equal, rectangular sub-areas. In each sub-area a 1 km transect was drawn,
      and digitalized on-screen in the GIS. Canine faeces (copros in Greek) were
      counted along the transects in 143 sub-areas. In these sub-areas, 415 copros were
      collected and examined. Out of the 143 sub-areas, 141 contained canine copros.
      The results of the negative binomial regression model showed a positive
      association between the number of copros and the human population density. Out of
      the total of 415 copros, 70 (16.9%) were positive for parasitic elements; eggs of
      Toxocara canis, Toxascaris leonina, Ancylostoma caninum and Trichuris vulpis were
      found, as well as oocysts of Isospora canis.

PMID- 16881414
TI  - Epidemiology and clinical features of Mediterranean spotted fever in Italy.
AB  - Mediterranean Spotted Fever is caused by Rickettsia conorii and is transmitted to
      humans by Rhipicephalus sanguineus, the common dog tick. It is characterized by
      the symptomatologic triad: fever, exanthema and "tache noire", the typical eschar
      at the site of the tick bite. In Italy the most affected region is Sicily. The
      seasonal peak of the disease (from June through September) occurs during maximal
      activity of immature stage ticks. Severe forms of the disease have been reported
      in 6% of patients, especially adults with one of the following conditions:
      diabetes, cardiac disease, chronic alcoholism, glucose-6-phosphate dehydrogenase
      deficiency, end stage kidney disease. The mortality rate may reach 2.5%. Oral or
      parenteral administration of tetracyclines or chloramphenicol represent the
      standard treatment. Recent studies indicate that oral clarithromycin and
      azithromycin could constitute an acceptable alternative for the treatment of the
      disease in children; furthermore, they could be recommended during pregnancy.

PMID- 16881415
TI  - Tick-transmitted diseases in dogs: clinicopathological findings.
AB  - In this article we describe the main clinicopathological findings of some tick
      transmitted diseases observed in Italy, due to Ehrlichia canis and Babesia canis,
      and most rarely Anaplasma phagocytophilum and Anaplasma platys. Canine monocytic
      ehrlichiosis (CME) is a multisystemic disorder that is characterized by various
      clinical signs. Acutely-infected dogs show various clinical and haematological
      abnormalities including fever, lymphadenopathy, anorexia, lethargy, depression
      and thrombocytopenia. Many dogs with CME evolve in to an asymptomatic or
      chronically symptomatic carrier states. In Italy there are very few cases of
      Canine Granulocytic Ehrlichiosis (CGE) and all are attributed to A.
      phagocytophilum. The early manifestations of CGE are usually mild and consist in
      acute onset of fever and depression with or without thrombocytopenia. Lameness
      due to polyarthritys is also possible. Other clinical manifestations most rarely
      described are very similar to those reported in chronic form of E. canis
      infections. There are very few studies about clinicopathological findings of
      canine babesiosis in Italy. In our country this infection is caused by Babesia
      canis (large form of parasite) subspecies B. canis canis and B. canis vogeli.
      These two subspecies are morphologically indistinguishable. Clinical signs
      reflect the intravascular and extravascular haemolysis due to the life cycle of
      the parasite. The most common haematological abnormalities found in canine
      babesiosis are anaemia and thrombocytopenia. It is important to point out that co
      infection between two or more agents is possible. In this case it is very
      difficult to attribute the clinical signs and haematological and/or biochemical
      abnormalities to a single specific agent.

PMID- 16881416
TI  - Ecology and epidemiology of tick-borne diseases: which role for the control?

PMID- 16881417
TI  - Acaricidal and repellent properties of permethrin, its role in reducing
      transmission of vector-borne pathogens.
AB  - Vector-borne pathogens causing canine vector-borne diseases (CVBD) are recognized
      as being of increasing importance in small animal clinics. The pathogens and
      their vectors (eg, fleas, ticks, mosquitoes and sand flies) have a global
      distribution. Their prevalence may vary depending on region, climate, hygiene and
      many other factors; however the risk of infection for companion animals in our
      highly developed and supposedly regulated environments will never be zero. Even
      in highly developed markets, with high socioeconomic standards, ectoparasites are
      still a threat to both pets and humans. One has to understand the complexity of
      arthropod biology and esp. the complex mechanisms of host seeking, attachment and
      skin penetration and finally feeding, to differentiate the various acaricides and
      their therapeutic as well as prophylactic properties. Prevention of arthropod
      bites is mainly by prevention of attachment and thus any engorgement if possible.
      To achieve this, acaricides with repellent properties, such as the synthetic
      pyrethroid permethrin are ideal compounds to reach this goal.

PMID- 16881418
TI  - Assessment of the efficacy of parasiticides for the control of tick infection in
      dogs under field conditions: what's new?
AB  - For their biological and ecological characteristics, ticks are vectors of the
      widest variety of pathogens causing tick-borne diseases (TBDs). Little
      information is available about the ways in which time spent by ticks to feed on
      hosts, transmission times and TBD prevention are related and it is exclusively
      limited to laboratory reports on adult stages. In particular, the time required
      by immature stages to transmit pathogens has not been determined for most TBDs.
      Considering their importance for animal and human health, effective control of
      immature ticks is advisable to reduce the damage ticks cause. Recently, the
      efficacy of a combination of imidacloprid 10%/permethrin 50% was compared with
      that of fipronil 10%/S-methoprene 9% against ticks when administered to naturally
      infected dogs. A semi-quantitative method was used to assess the methodological
      parameters to calculate drug efficacy on immature stages. On adult ticks, the
      efficacy of both products was high and overall very similar, whereas for the
      immature stages the combination of imidacloprid 10% and permethrin 50% had a
      higher efficacy than fipronil 10% and methoprene 9% throughout the observation
      period (statistically significant difference on day + 28 only). The semi
      quantitative method proposed for the evaluation of immature stages can be
      considered a useful tool for calculating the efficacy of a drug in the field. Due
      the important role of immatures in the spread of TBDs, the immature tick load
      should be calculated to assess the efficacy of acaricidal products both under
      laboratory and field conditions.

PMID- 16881419
TI  - Dog tick-borne diseases in Sicily.
AB  - In Sicily many tick borne diseases are endemic, in particular way those that see
      like main carrier ticks that prefer, for their vital cycle, climatic conditions
      characterized by high temperatures and a warmth-humid atmosphere. The more
      important pathologies transmitted by ticks causing diseases in dogs are
      babesiosis and ehrlichiosis. Borrelia burgdorferi, Anaplasma phagocytophilum,
      Rickettsia conorii, Coxiella burnetii and tick transmitted encephalitis virus
      assume particular relevance because they are agents of zoonosis. Our centre,
      C.R.A.Ba.R.T, have conducted many researches and carried out many tests for
      diagnostic aim in order to estimate the spread of the main tick borne diseases in
      Sicilians' dogs. A study lead on 342 dogs has evidenced seroprevalence for
      Babesia canis, Ehrlichia canis and Rickettsia respective of 5.17%, 21.70% and
      53.43%. A study on zoonotic agent seroprevalences in dogs gave the following
      percentages: C. burnetii 31.50%, R. conorii 73.60% and A. phagocytophilum 32.80%.
      The data carried out from IZS Sicily diagnostic service on 5,634 tests done in
      2004-2005, confirm the experimental results on the presence of B. canis, E.
      canis, R. conorii, A. phagocytophilum, C. burnetii, Rickettsia spp., Anaplasma
      spp. and Ehrlichia spp. in all the Sicilian areas.

PMID- 16881420
TI  - Nasal bone hypoplasia in trisomy 21 at 15 to 24 weeks' gestation in A high risk
      Thai population.
AB  - OBJECTIVE: To assess the utility of nasal bone hypoplasia in the detection of
      fetuses with trisomy 21 in the second trimester in a high risk Thai population.
      MATERIAL AND METHOD: A prospective study involving pregnant women undergoing
      amniocentesis due to increased risk of aneuploidy from January 2005 to December
      2005. Fetal biometry and nasal bone measurements were obtained at the time of
      amniocentesis. Linear regression model and diagnostic tests were analyzed using
      the SPSS computer program. RESULTS: A total of 407 fetuses were evaluated. In
      euploid fetuses, the Nasal Bone Length (NBL) increased linearly with advancing
      gestational age. Fetuses with Down syndrome had a significantly higher proportion
      of NBL below the 5th centile when compared with normal fetuses (p < 0.05). The
      optimal nasal bone threshold associated with trisomy 21 is a BiParietal
      Diameter/Nasal Bone Length (BPD/NBL) ratio of 10 or greater, yielded a
      sensitivity of 80%, specificity of 86% for detection of trisomy 21. CONCLUSION:
      Nasal bone hypoplasia is associated with an increased risk of Down syndrome in
      the presented population.

PMID- 16881421
TI  - A successful strategy for Preimplantation Genetic Diagnosis of beta-thalassemia
      and simultaneous detection of Down's syndrome using multiplex fluorescent PCR.
AB  - OBJECTIVES: Preimplantation Genetic Diagnosis (PGD) is an alternative to prenatal
      diagnosis providing couples the chance to start a pregnancy with an unaffected
      fetus. The objective of the present study was to develop and apply quick,
      sensitive and accurate single cell PCR protocols for PGD of beta-thalassemia and
      Down's syndrome detection. MATERIAL AND METHOD: Two couples carrying beta
      thalassemia codon41-42 mutation underwent routine IVF procedures. Embryo biopsy
      was performed on Day-3 post-fertilisation and single cell multiplex fluorescent
      PCR was employed for mutation analysis, contamination detection and diagnosis of
      trisomy 21 cases. RESULTS: Seventeen embryos were tested in two clinical PGD
      cycles. This resulted in the first birth following PGD for a single gene disorder
      in Thailand and South East Asia, confirmed by prenatal testing. Two embryos were
      shown to be affected by Down's syndrome. CONCLUSION: Successful strategy for PGD
      of beta-thalassemia and Down's syndrome detection using multiplex fluorescent PCR
      was introduced.

PMID- 16881422
TI  - Effectiveness of 400 or 600 micrograms of vaginal misoprostol for terminations of
      early pregnancies.
AB  - OBJECTIVES: To compare the effectiveness and side effects of transvaginal
      application of 400 or 600 ug of misoprostol for termination of pregnancy. STUDY
      DESIGN: A prospective randomized single-blinded trial. SETTING: Department of
      Obstetrics & Gynecology, Bhumibol Adulyadej Hospital. MATERIAL AND METHOD: One
      hundred-and-twenty-five pregnant women with less than 20 weeks gestational, at
      Bhumibol Adulyadej Hospital from June 1, 2003 to May 31, 2004 were recruited. The
      termination of pregnancy had been suggested by the obstetrician and the decision
      was made by the patient and her husband. The samples were randomized into 2
      groups. Group 1 had 65 patients and 400 ug of misoprostol was applied three times
      in a 6 hour interval. Group 2 had 60 patients and 600 ug of misoprostol was
      applied in the same manner. Both groups were observed and evaluated within 24
      hours. MAIN OUTCOME MEASURES: Rate of complete abortion and side effects of both
      400 and 600 microg misoprostol within 24 hours. RESULTS: No statistical
      significant difference was found in the general characteristics of both sample
      groups. Group 1 had an abortion rate of 38.3% while group 2 had an abortion rate
      of 56.92%. This was statistically significant (p < 0.05). The time interval after
      insertion to complete abortion was 9.15 +/- 6.09 hours in group 1 and 8.85 +/-
      4.68 hours in group 2. Side effects, such as fever, lower abdominal pain, massive
      vaginal bleeding and diarrhea showed no statistical difference (p > 0.05).
      CONCLUSION: Transvaginal application of 600 ug misoprostol (3 times every 6
      hours) caused a higher rate of complete abortion compared with an application of
      400 ug misoprostol. The side effect of both groups showed no statistical
      difference.

PMID- 16881423
TI  - Tumor persistence in high grade squamous intraepithelial lesion patients with
      positive surgical margin post loop electrosurgical excision procedure.
AB  - OBJECTIVE: To determine the rates of persistent and recurrent tumors in patients
      with High Grade Squamous Intraepithelial Lesion (HSIL) who had positive surgical
      margin from Loop Electrosurgical Excision Procedure (LEEP). MATERIAL AND METHOD:
      Clinical and pathological data of all women who underwent LEEP procedures and
      revealed HSIL lesions with positive surgical margin between July 1997 and
      December 2004 were recorded. RESULTS: Histologic diagnoses of HSIL with positive
      surgical margin were found in 95 cases during the study period. Residual diseases
      were identified at ectocervical margins in 46 cases (48.4%), endocervical margin
      in 26 cases (27.4%), and both margins in 23 cases (24.2%). Subsequent
      hysterectomy was performed in 58 cases (61.0%). The remaining 37 cases (38.9%)
      underwent periodic follow-up with the median follow up period of 11 months
      (range, 1-74 months). Persistent diseases were identified in 18 of 58
      hysterectomized cases but none in 37 follow-up cases. Recurrent disease was
      identified in only one case in the follow-up group. Overall the rates of
      persistent and recurrent disease were found in 18.9% and 1.1% respectively.
      CONCLUSION: In HSIL patients with positive surgical margin from LEEP the rate of
      persistent disease was 18.9%, while the rate of recurrence was 1.1%.

PMID- 16881424
TI  - A randomized, prospective study comparing the use of the missile trocar and the
      pyramidal trocar for laparoscopy access.
AB  - BACKGROUND: The missile trocar was developed for smooth abdominal penetration of
      the primary port. It contains a longitudinal tunnel connecting the abdominal
      cavity with the outside. OBJECTIVE: To evaluate the efficacy of the missile
      trocar compared with the traditional method using the Veress needle. MATERIAL AND
      METHOD: The times required to enter the abdominal cavity and the difficulty of
      the procedure were compared with the traditional Veress needle. A blind technique
      was used on 100 consecutive patients in a randomized fashion. RESULTS: The
      missile trocar technique took 2.7 +/- 1.6 minutes to perform compared with 3.9 +/
      1.3 min in the Veress needle group (p = 0.001), and the difficulty of the
      procedure was 2.1 +/- 1.9 cm (p = 0.433) rated from 10-cm scale. No carbon
      dioxide leakage or serious complications occurred in any patient. CONCLUSION: The
      results of the present study indicate that a long-tip missile trocar technique
      may be used safely when the technique is fully understood. This procedure is a
      relatively quick alternative approach for laparoscopy.

PMID- 16881425
TI  - Difference in isokinetic strength of the muscles around dominant and nondominant
      shoulders.
AB  - BACKGROUND: Muscle training usually plays an important role in the treatment of
      shoulder disorders. Clinicians traditionally predict the pre-injury strength of
      an injured shoulder by using the contralateral uninjured side as the baseline
      data. OBJECTIVE: The primary purpose of the present study was to determine the
      difference in isokinetic peak torque of dominant and nondominant shoulders.
      MATERIAL AND METHOD: Both shoulders of 39 healthy subjects (24 men, 15 women)
      were tested isokinetically by using the CON-TREX MJ dynamometer at two angular
      velocities (60 and 180 degrees/sec) during abduction, adduction, flexion,
      extension, internal rotation and external rotation. RESULT: There were
      statistical differences of contralateral peak torque in almost all directions of
      shoulder muscle contractions except in shoulder flexion at both speeds. Peak
      torque of shoulder adduction, extension, and internal rotation were greater in
      the dominant side. Shoulder abduction and external rotation peak torque were
      greater in the nondominant side. CONCLUSION: Therefore, clinicians should not
      directly use the isokinetic strength of the contralateral shoulder as normal
      baseline data for an injured side without consideration.

PMID- 16881426
TI  - Comparison of efficacy of 1% silver sulfadiazine and Acticoat for treatment of
      partial-thickness burn wounds.
AB  - BACKGROUND: Acticoat (Smith & Nephew, Hull, UK) is a silver-coated dressing
      reported to reduce infection and exhibit antimicrobial activity in wounds.
      OBJECTIVE: The purpose of the present study was to compare the efficacy
      ofacticoat and 1% silver sulfadiazine (1% AgSD) for treatment of partial
      thickness burn wounds. MATERIAL AND METHOD: The authors reviewed 50 patients who
      had partial thickness burn wounds less than 25% admitted to Siriraj Burn Unit
      from May 2002 to September 2005. All patients were divided into 2 groups: the
      acticoat treated group (25 patients) and the 1% silver sulfadiazine treated group
      (25 patients). The 2 groups were compared for the etiology of burn wound,
      demographic data including age, sex, % Total Body Surface Area burn (TBSA%),
      cultured organisms, wound infection and outcome of Length Of hospital Stay (LOS)
      and level of pain. RESULTS: The authors found no significant differences in age,
      TBSA (%) between both groups. 7 patients (28%) developed wound infection. There
      were no differences in wound infection and LOS between both groups (p > 0.05).
      All of the patients who developed wound infection responded well to targeted
      topical and systemic antibiotic treatment. The 1% AgSD treated group (6 of 25,
      24%) obtained more split thickness skin graft to close the granulation defects
      compared to patients who were treated with acticoat (4 of 25, 16%) but no
      statistical significance, p = 0.32). Average pain scores in the acticoat treated
      groups were significantly lower than the 1% AgSD treated group (4 +/- 0.6 versus
      5 +/- 0.7, respectively). CONCLUSION: The present study confirms the efficacy of
      acticoat treatment in partial thickness burn wound. The authors conclude that
      acticoat has an advantage of limiting the frequency of replacement of the
      dressing and provides a less painful alternative to wound care with 1% AgSD with
      comparable incidence of burn wound infection. This is due to its long wear time
      and the ease of application and removal.

PMID- 16881428
TI  - Thyrotoxicosis in children: treatment and outcome.
AB  - OBJECTIVES: To study the treatment modalities and the outcome of treatments of
      children with thyrotoxicosis or Graves' disease. MATERIAL AND METHOD: A
      retrospective study of 56 patients diagnosed with thyrotoxicosis from January
      1992 to December 2004 was conducted. There were 44 girls and 12 boys (female to
      male ratio 3.7:1). The average age at diagnosis was 11.9 +/- 3.4 years. RESULTS:
      All patients were initially treated with antithyroid drugs, either
      propylthiouracil (n = 53) or methimazole (n = 3). All patients achieved
      euthyroidism within 8.4 +/- 3.3 weeks. Eleven patients are still on the
      treatment, and 45 patients have completed the treatment. Of these 45 patients, 38
      (84.4%) remitted after antithyroid drug treatment of an average duration of 37.4
      +/- 16.5 months (range 12-90), 4 patients (8.9%) chose radioactive iodine
      treatment and three patients (6.7%) underwent thyroidectomy. Of the 38 patients
      remitted with antithyroid drugs, eleven (28.9%) relapsed within 4-24 months. The
      relapsed patients remitted with a second course of antithyroid drugs in three
      patients, underwent radioactive iodine in seven patients, and thyroidectomy in
      one patient. Therefore, of the total 45 patients who had completed the treatment,
      30 patients (66.7%) remitted with antithyroid drugs, eleven patients (24.4%)
      received radioactive iodine, and four patients (8.9%) underwent thyroidectomy.
      Using stepwise multivariate logistic regression, the authors could not identify
      any factors (including age, gender, family history of thyroid diseases, size of
      goiter, level of free T4, dosage and duration of antithyroid drugs) that would
      predict the remission of thyrotoxicosis with antithyroid drugs. CONCLUSION:
      Antithyroid drugs should remain the first-line therapy for treatment of
      thyrotoxicosis in children with a remission rate of 66.7%. The patients who are
      noncompliant or relapse after treatment with antithyroid drugs should be treated
      with radioactive iodine.

PMID- 16881427
TI  - A comparison of patient pain during cataract surgery with topical anesthesia in
      Prechop Manual Phacofragmentation versus phacoemulsification.
AB  - OBJECTIVE: To compare the pain level and complications during cataract surgery
      with topical anesthesia in Prechop MPF versus phacoemulsification. STUDY DESIGN:
      Prospective randomized comparative study. MATERIAL AND METHOD: One hundred
      patients, undergoing small incision cataract surgery under topical anesthesia,
      were allocated randomly to perform Prechop MPF (n = 50) or phacoemulsification (n
      = 50). Patients were asked to rate their pain level on a 10-point visual analog
      pain scale during the administration of the anesthetic, during the surgery and
      after surgery. The surgeon recorded his subjective assessment of patient
      cooperation and surgical complications. RESULTS: The mean pain score during
      surgery was 1.64 +/- 1.48 (SD) in the prechop MPF group and 0.92 +/- 1.34 (SD) in
      the phacoemulsification group. The difference between groups was statistically
      significant (p = .001). There was no significant difference in pain scores for
      delivery of anesthesia (p = .077), or after surgery (p = .221) and no significant
      difference in patient cooperation (p = .446) and surgical complications in either
      group. CONCLUSION: Patients having cataract surgery under topical anesthesia in
      the prechop MPF group had more intraoperative pain than patients in the
      phacoemulsification group. However there was no significant difference in patient
      cooperation and surgical complications between the groups.

PMID- 16881429
TI  - Use of HIV Postexposure Prophylaxis in healthcare workers after occupational
      exposure: a Thai university hospital setting.
AB  - BACKGROUND: PostExposure Prophylaxis (PEP) is widely used after exposures to
      Human Immunodeficiency Virus (HIV) to reduce the risk of infection in the
      healthcare setting. Few data are available on the safety and tolerability of Anti
      Retro Viral drugs (ARV) among Health Care Workers (HCWs) who are prescribed
      prophylaxis. OBJECTIVE: To collect information about the safety and compliance of
      taking ARV for HIV PEP among HCWs. MATERIAL AND METHOD: Retrospective review on
      registry data regarding occupational HIV exposures, the PEP regimens used, and
      the adverse events associated with PEP was performed. RESULTS: During a five year
      period, 820 episodes with occupational blood or body fluid exposures were
      reported Nurses (27%) were the largest group at risk. The most common type of
      exposure was percutaneous injuries (82%). Only 125 (15%) HCWs had occupational
      exposures to HIV, 64 HCWs were prescribed HIV PEP and 32 (50%) HCWs did not
      complete the PEP regimen as initially prescribed. The commonly prescribed ARV was
      zidovudine (38%), lamivudine (33%), and indinavir (11%). Overall, 18 (28%) HCWs
      reported symptoms while on PEP such as nausea (89%), vomiting (55%), and
      dizziness (39%). None of the HCWs had HIV seroconversion. CONCLUSIONS: Adverse
      effects from HIV PEP were very common. Clinicians prescribing HIV PEP need to
      discuss with HCWs about PEP efficacy and side effects. Education efforts aimed at
      occupational exposure prevention are still important issues.

PMID- 16881430
TI  - Transtympanic gentamicin treatment in Meniere's disease: a preliminary report.
AB  - OBJECTIVE: To evaluate the effectiveness of transtympanic gentamicin treatment in
      Meniere's disease. MATERIAL AND METHOD: The present study is a prospective study
      of 8 patients in Ramathibodi Hospital who had transtympanic gentamicin treatment
      of Meniere's disease by fixed dose regimen of 12 injections during a period of 4
      days. The committee on hearing and equilibrium guidelines for reporting treatment
      results in Meniere's disease of the American Academy of Otolaryngology and Head &
      Neck Surgery (1995) were used. Paired t-test or Wilcoxon Signed Ranks Test was
      used for statistical comparisons. RESULTS: Among 8 patients, there were 2 males
      and 6 females. All patients (100%) had either complete (37.5%) or substantial
      (62.5%) control of vertigo. Disability was also improved in all of the subjects
      (100%). Tinnitus was improved in 62.5%. Their tinnitus score and functional level
      scale were much improved with statistical significance (p = 0.001, p < 0.005,
      respectively). Hearing was unchanged in 87.5% and slightly worse in 12.5%. This
      was not significant. CONCLUSION: Transtympanic gentamicin treatment was found to
      be an effective treatment option for patients with disabling or intractable
      Meniere's disease, with a low incidence of hearing loss. The use of this method
      appears to be practical and may replace the vestibular surgery.

PMID- 16881431
TI  - Clearance of vancomycin during high-efficiency hemodialysis.
AB  - BACKGROUND: Vancomycin is commonly used for the treatment of MRSA infections in
      critically ill patients with renal diseases. Vancomycin is mainly eliminated
      through the kidney. Its excretion is therefore substantially reduced in severe
      renal impaired patients. Although several studies have demonstrated that
      significant amounts of vancomycin are removed during High-Flux/High-Efficiency
      Hemo Dialysis (HF/HEHD), more data are required to optimize clinical
      applications. OBJECTIVE: Predict the appropriate vancomycin intradialytic dosage
      and dosing interval among patients receiving HEHD. MATERIAL AND METHOD: Twenty
      patients who were receiving HEHD with cellulose triacetate dialyzer were included
      to determine the vancomycin intradialytic clearance. Two patients were included
      twice and one patient was included three times due to reinfections. This gave
      rise to 24 patient-times. The study was carried out at Songklanagarind Hospital
      between January 2003 and March 2004. RESULTS: In a prospective opened label
      design, each patient received 1g vancomycin, 1 hour infusion, immediately after
      completion of HEHD. Six scheduled blood samples were drawn as follows: (1) 60
      minutes following completion of vancomycin infusion (Cmax); (2) immediately
      before starting the second HEHD; (3) 2 hours after starting the second HEHD; (4)
      immediately after completion of the second HEHD; (5) immediately before starting
      the third HEHD; and (6) immediately after the third HEHD ended (Cmin). The
      authors measured vancomycin serum levels using HPLC technique. The serum
      concentrations were used to calculate all relevant pharmacokinetic parameters.
      The pharmacokinetic parameters (mean +/- SD) were: intradialytic clearance (CLHD)
      93.4 +/- 37.1 mL/min; intradialytic elimination rate constant (k) 1.1 +/- 0.5 hr(
      1); overall elimination half-life (t(1/2)) 77.1 +/- 37.8 hr; volume of
      distribution (Vd) 82.1 +/- 40.3 L; Cmax 25.8 +/- 8.12 mg/L (range 12.04-48.80);
      Cmin 6.2 +/- 3.1 mg/L; and % removal during the second HEHD 37.9 +/- 12.9.
      Subtherapeutic levels were found in 66.7% (16/24) and 91.6% (22/24) of patients
      after the second and the third HEHD, respectively. CONCLUSION: HEHD with
      cellulose triacetate dialyzer removes significant amount of vancomycin. Based on
      the authors' findings, a loading dose of 1 g, and 500 mg after every subsequent
      HEHD is recommended.

PMID- 16881432
TI  - Assessment of dermographism at different anatomical regions by dermographometer.
AB  - OBJECTIVE: Classic dermographism refers to the ability of the skin to produce a
      linear wheal with a scratch pressure of 4,900 gm/cm2. The authors manufactured a
      dermographometer to have precise and consistent measurement and tested it on
      different body regions to find the best location. MATERIAL AND METHOD: Twenty two
      patients with dermographism were enrolled. The pressure was applied to the volar
      aspect of the left forearm using the dermographometer and to the right forearm by
      the pen head. Then the pressure was applied to the upper back, abdomen, and shin
      using the dermographometer. The time onset and size of wheal, erythema and flare
      were recorded. RESULT: The positive yield at the left forearm by the
      dermographometer was 72.7% and the positive yield at the right forearm by the pen
      head was 68.2%. The positive yield of back, abdomen and shin were 68.2%, 68.2%
      and 13.6%, respectively. CONCLUSION: The dermographometer gave a comparable
      positive yield in diagnosing dermographism with the pen head and the
      dermographometer. The volar forearm, back and abdomen are the sensitive areas to
      produce dermographism while the shin is the least sensitive area. The site of the
      body that is most appropriate in testing is the forearm as it is easy to
      approach.

PMID- 16881433
TI  - Assessment of hormonal and metabolic effects of dietary fiber in young Thai
      women.
AB  - OBJECTIVE: To investigate whether daily dietary fiber intake at the reference
      level has any impact on studied hormones in a population of Thai women. MATERIAL
      AND METHOD: Twenty-eight healthy Thai women (aged 18-20 years, BMI 18.5-25 kg/m2)
      with a history of regular menstrual cycles committed themselves to prepared food
      without changing the usual ratio of three major macronutrients. Dietary fiber
      from natural source at the amount of 8-10 g/day equal to their regular
      consumption was added to their daily diet for one menstrual cycle, then,
      increased to be 25-30 g/day for another 2 successive cycles. A single blood
      sample on midluteal day (day 18-23) was obtained in all three cycles. Plasma
      luteinizing hormone, follicle stimulating hormone, prolactin, estradiol,
      progesterone, cortisol, and insulin together with total cholesterol, high-density
      lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides
      were analyzed. RESULTS: The measured hormones and lipids did not change
      significantly when compared between a control and two experimental cycles (p >
      0.05). CONCLUSION: Short-term consumption of 25-30 g/day fiber diet as
      recommended by the Reference Daily Intake (RDI) in a Thai population did not
      alter the studied hormones and lipids thus did not create any health problems.

PMID- 16881434
TI  - Dental caries and periodontitis associated with betel quid chewing: analysis of
      two data sets.
AB  - BACKGROUND: Not much research evidence concerning the relationship between betel
      quid chewing and oral health has been established although betel quid chewing is
      a common practice among people in many Asian countries including rural areas of
      Thailand. OBJECTIVE: The present study employed two existing data sets to
      evaluate the association between betel quid chewing and oral diseases. MATERIAL
      AND METHOD: The study populations for phase I comprised a total of 796 females,
      aged 30-89 years, residing in five districts of Khon Kaen province, Thailand
      during 1990-91. In phase II, there were 2,253 females, aged 31-86 years, residing
      in Chonnabot district, Khon Kaen province, Thailand during 1992-94, respectively.
      The data were obtained through oral examination and interview. The analyses
      employed descriptive, bivariate, and multivariable logistic regression. RESULTS:
      Findings from final multivariable logistic regression models revealed the inverse
      relationship between betel quid chewing and dental caries adjusting for other
      variables. In addition, results from the final multivariable logistic regression
      models predicting periodontitis showed that betel quid chewing was directly
      associated with periodontitis in the presence of several confounding factors. The
      consistent findings from both data sets suggest that although betel quid chewing
      may reduce dental caries, it was directly related to periodontitis and enhanced
      the possibility of increasing tooth loss. CONCLUSION: Therefore, preventive
      programs aiming at discouraging Thai people from chewing betel quid should be
      established to preserve favorable oral health.

PMID- 16881435
TI  - Factors associated with dual form of malnutrition in school children in Nakhon
      Pathom and Bangkok.
AB  - OBJECTIVE: The present study examined the influence of family characteristics and
      maternal feeding practices on eating behaviors, food consumption and nutritional
      status of children living in 6 districts of Nakhon Pathom province and 3
      surrounding districts of Bangkok. MATERIAL AND METHOD: One hundred and ninety
      nine families were enrolled in the present study. Four specific mother-child pair
      groups were purposively selected: 62 obese child/overweight mother pairs, 49
      obese child/ normal weight mother pairs, 37 wasted child/overweight mother pairs,
      and 51 normal weight child/normal weight mother pairs. Anthropometric
      measurements were performed on all subjects. Biological data, socioeconomic
      status, maternal feeding practices, as well as eating and lifestyle behaviors of
      the children were obtained from mothers and children using structured
      questionnaires and interviews. RESULT: Most mothers from all groups, 40.8%-62.2%,
      had a primary education, were non-manual workers, with families containing 4-6
      persons per household, and a family income of < or = 20,000 baht per month.
      Multivariate logistic regression analysis showed that maternal overweight prior
      to pregnancy (OR11.85, 95%CI 2.16-64.99) child's high birth weight (OR 4.53,
      95%CI 1.09-18.73) as well as maternal control over the consumption of high
      caloric food (OR13.07, 95%CI 4.08-41.86) and large amounts of food consumed by
      the children (OR12.58, 95%CI 4.30-36.80) were significant factors associated with
      childhood obesity. Compared to normal weight children, a higher proportion of
      obese children were not breast-fed and a higher proportion of normal weight
      mothers controlled the consumption of high caloric food in their obese children.
      Overweight mothers with wasted children also controlled their children's food
      intake. Higher proportion of wasted children had a higher snack consumption
      frequency but lower energy food intake than the normal weight children.
      CONCLUSION: Understanding the underlying causes of dual form of malnutrition in
      the households would have implication for policy makers to address and implement
      a nutrition action plan. It is suggested that a malnutrition, (under and over
      nutrition) prevention program must involve strategies within families that focus
      on providing nutrition education and the powerful guidance to help parents foster
      appropriate patterns of food choice and eating in their children. Promotion of
      increased physical activity in children is also essential. These strategies are
      aimed to promote the optimal child's weight and health.

PMID- 16881436
TI  - Communicating hydrocephalus as a complication of eosinophilic
      meningoencephalitis.
AB  - The authors reported an adult patient with communicating hydrocephalus in
      eosinophilic meningoencephalitis. He presented with localized peritonitis and
      then developed eosinophilic meningoencephalitis. Angiostrongylus cantonensis was
      the causative agent. This was confirmed by the positive serology test. His
      consciousness did not recover after supportive treatment. The MRI of the brain
      showed diffuse enlargement of the ventricular system two weeks after the
      diagnosis was made. The parameters for hydrocephalus were measured and were
      compatible with the Gyldensted's criteria.

PMID- 16881437
TI  - Reversible posterior leukoencephalopathy caused by azathioprine in systemic lupus
      erythematosus.
AB  - The authors report a case of systemic lupus erythematosus with posterior
      leukoencephalopathy who presented with headache, tonic-clonic seizure, loss of
      consciousness and bilateral loss of vision, after taking azathioprine for three
      weeks. The patient had hypertension with normal eye grounds. The brain CT showed
      a hypodensity lesion at both bilateral occipital lobes, mainly in the white
      matter The symptoms and follow-up MRI were improved after the control of
      hypertension and discontinuation of azathioprine.

PMID- 16881438
TI  - Spontaneous reseal of ruptured membranes after genetic amniocentesis.
AB  - BACKGROUND: Rupture of membranes is an uncommon complication of genetic
      amniocentesis. The risk of ruptured membranes is reported as 1-1.2%. CASE:
      Genetic amniocentesis complicated by ruptured membranes was diagnosed in a 31
      year-old woman. The membranes resealed after 48 hours with conservative
      management and the pregnancy ended with a favorable outcome. CONCLUSION:
      Spontaneous reseal of ruptured membranes after genetic amniocentesis can occur
      with conservative management and end with a favorable pregnancy outcome.

PMID- 16881439
TI  - Noninvasive diagnosis of fetal anemia and fetal intravascular transfusion
      therapy: experiences at Siriraj Hospital.
AB  - Traditionally, when fetal hydrops are found along with certain markers indicating
      fetal anemia, fetal blood sampling would be performed through cordocentesis to
      confirm the diagnosis. This procedure, however comes with an inherent risk of
      losing the whole pregnancy. When anemia was verified, treatment options were
      limited and the prognosis was grim. In this article, the authors described their
      experiences of using prenatal Doppler studies as a noninvasive venue in the
      diagnosis and treatment of fetal anemia. Once the diagnosis of fetal anemia is
      made, the patient will be asked to undergo an algorithm to investigate the
      definite cause of anemia, along with simultaneous ultrasound-guided intravascular
      fetal transfusion in selected cases. The authors selected two cases of fetal
      anemia of different etiologies and treatment outcomes to demonstrate the
      significance of early diagnosis and intervention. Review of the relevant medical
      literatures and the proposed algorithms were also provided.

PMID- 16881440
TI  - Spontaneous intra-abdominal bleeding during pregnancy.
AB  - Two cases of spontaneous hemoperitoneum caused by ruptured uterine vessels plexus
      during the second and third trimester of pregnancy were reported. All presented
      with acute abdominal pain. Emergency exploratory laparotomy and suture-ligation
      were performed One case had a recurrent intra-abdominal bleeding. The outcomes
      were good. One infant had complications from prematurity and both were discharged
      in good condition.

PMID- 16881441
TI  - Symptomatic Tarlov cyst: report and review.
AB  - Tarlov or perineural cysts are nerve root cysts found most commonly at the sacral
      spine level arising between covering layers of the perineurium and the
      endoneurium near the dorsal root ganglion. The cysts are relatively rare and most
      of them are asymptomatic. Some Tarlov cysts can exert pressure on nerve elements
      resulting in pain, radiculopathy and even multiple radiculopathy of cauda equina.
      There is no consensus on the appropriate therapeutic options of Tarlov cysts. The
      authors present a case of two sacral cysts diagnosed with magnetic resonance
      imaging. The initial symptoms were low back pain and sciatica and progressed to
      cauda equina syndrome. Surgical treatment was performed by sacral laminectomy and
      wide cyst fenestration. The neurological deficits were recovered and had not
      recurred after a follow-up period of nine months. The literature was reviewed and
      discussed. This is the first reported case in Thailand.

PMID- 16881442
TI  - Bilateral leiomyoma of epididymides.
AB  - Leiomyoma is a relatively uncommon neoplasm of the epididymis derived from smooth
      muscle cells. A case of primary leiomyomas simultaneously occurring in both
      epididymides is reported in a 58-year-old man, clinically presenting painless
      intra-scrotal masses. The examination of the epididymis characterizes clinically
      by a firm solid, well-circumscribe mass, and histological spindle cells arranged
      in interlacing bundles with varying admixtures of fibrous and hyalinized
      connective tissue. Clinical, histopathologic and immunohistopathologic features,
      with briefly reviewed relevant literatures describing 7 cases of bilateral
      leiomyoma of epididymides are discussed. The patients with the mean age of 56.6
      years (range 47-62 years) had epididymal mass measuring 5 to 75 millimeters (mean
      21.3 millimeters). This is the first reported description of bilateral leiomyoma
      of epididymides in Thailand.

PMID- 16881443
TI  - Embryonic stem cell bank.
AB  - Embryonic stem cell bank is a cornerstone for stem cell research. It is providing
      essential resources to support advances in research in this challenging field
      that promises broad-ranging cell and tissue therapy. It is important to make good
      quality and well characterized embryonic cell lines that will be available for
      both research and clinical purposes. This article provides a concise summary on
      embryonic stem cell banking processes from cell line characterization, storage,
      quality assurance, safety testing, distribution, and post-distribution
      monitoring. It also states the importance of an international network and
      collaboration for technology and knowledge transfer Moreover, the Bank should
      play a substantial role as a national reference and a training center for stem
      cell research.

PMID- 16881444
TI  - Global HIV cohort studies among injecting drug users and future vaccine trials.
AB  - The author reviewed the most recent data on the global HIV epidemic among
      Injecting Drug Users (IDUs) and summarized potential cohorts of IDUs that could
      participate in future HIV vaccine trials. An additional review of molecular
      epidemiology was described by region for better understanding of the state of the
      epidemic and potential impact on the development of HIV preventive strategies.
      From 1980 to mid-2005, increases in the prevalence rate were observed in many
      countries in Asia, Eastern Europe, Latin America and the Caribbean, and Canada
      among IDU. The HIV epidemics in some of these countries could rapidly expand if
      appropriate preventive measures are not undertaken. From cohort studies, high
      incidence rates were identified in China, Thailand, Canada, and Spain. Several
      studies also showed high participation and retention rates of injecting drug
      users that emphasized their potential to be volunteers in future vaccine trials.

PMID- 16881445
TI  - Risk factors associated with language development problems in childhood--a
      literature review.
AB  - BACKGROUND: Children with language problems are found to have a higher risk for
      future academic difficulties and learning disabilities. Conclusions from related
      literature were in many ways inconsistent. OBJECTIVE: To identify systematically,
      the existing literature, and factors that influence language development in
      children. MATERIAL AND METHOD: Databases of scientific literature were screened
      through the internet for publications that involved factors effecting language
      development in childhood. Hard copies of related scientific journals were also
      sought for relevant topics by the authors, making use of reference lists of
      publications, and citation search. Studies were included if they were published
      since 1984 and investigated factors that affect language development in children.
      They were excluded if they were not original research articles. RESULTS: Fifteen
      studies were included for this review--a case-control study, a cross-sectional
      study, and thirteen longitudinal studies. Most studies demonstrated that the
      following factors affect language development--antenatal care, Apgar scores,
      birth weight, premature delivery, birth order, parental education, environmental
      factors, gender of the children, and family history with specific language
      impairment. CONCLUSION: Perinatal/postnatal and environmental factors influence
      language development. Such factors should be taken into account as confounding
      factors in further language development studies.

PMID- 16881447
TI  - Informed consent and potential bias.

PMID- 16881448
TI  - Pregnancy in biliary atresia after Kasai operation complicated by portal
      hypertension.

PMID- 16881446
TI  - Standard of medical profession.

PMID- 16881450
TI  - [Leukemias].

PMID- 16881451
TI  - [Hodgkin's disease or lymphoma].

PMID- 16881452
TI  - [Willebrand disease].

PMID- 16881453
TI  - [Anemias].

PMID- 16881454
TI  - [For quality of transition between pediatric and adult services. Interview by
      Sylvie Warnet].

PMID- 16881455
TI  - [Hemoculture].

PMID- 16881456
TI  - [Making an extended care facility a real place to live! Interview by Sylvie
      Warnet].

PMID- 16881458
TI  - [How to change a simple dressing].

PMID- 16881457
TI  - [Dressing sets for unique uses].

PMID- 16881459
TI  - [They call them "doulas" or "birth attendants"].

PMID- 16881460
TI  - [Erythropoietin beta].

PMID- 16881461
TI  - [Echography, an efficacious and inoffensive technique].

PMID- 16881462
TI  - Researchers and clinicians: a growing divide or narrowing gap?

PMID- 16881463
TI  - Initial changes in posterior talar glide and dorsiflexion of the ankle after
      mobilization with movement in individuals with recurrent ankle sprain.
AB  - STUDY DESIGN: A double-blind randomized crossover experimental study with
      repeated measures, including a no-treatment control condition. OBJECTIVE: To
      evaluate the initial effect of 2 mobilization with movement (MWM) treatment
      techniques performed in weight bearing and non-weight bearing on posterior talar
      glide and talocrural dorsiflexion in individuals with recurrent lateral ankle
      sprain. BACKGROUND: MWM treatment techniques are commonly used in the treatment
      of musculoskeletal pain, such as lateral ankle sprain. Recent evidence indicates
      that a lack of posterior talar glide and weight-bearing ankle dorsiflexion are
      common physical impairments in individuals with recurrent ankle sprains. MWM of
      the ankle joint involves the application of a combined posterior talar glide
      mobilization and active dorsiflexion movement. The recurrent ankle sprain injury
      and the MWM treatment techniques for the ankle seemingly provide an appropriate
      model to further evaluate the effects and mechanism(s) of action of the MWM
      treatment techniques in a way that they have not been tested to date. METHODS:
      Sixteen subjects (mean +/- SD age, 19.8 +/- 2.3 years) with a history of
      recurrent lateral ankle sprain and deficits in posterior talar glide (71%) and
      weight-bearing dorsiflexion (34%) were studied. A within-subjects study design
      was used to evaluate the effect of 2 independent variables: treatment conditions
      (weight-bearing MWM, non-weight-bearing MWM, and a no-treatment control group)
      and time (pretreatment and posttreatment) on the dependent variables of posterior
      talar glide and weight-bearing dorsiflexion. RESULTS: Both the weight-bearing and
      non-weight-bearing MWM treatment techniques significantly improved posterior
      talar glide by 55% and 50% of the preapplication deficit between affected and
      unaffected sides, respectively, which was significantly greater than that of the
      control group (P<.001). The weight-bearing and non-weight-bearing MWM treatment
      techniques improved weight-bearing dorsiflexion by 26% (P<.017), compared to 9%
      for the control condition. The change in posterior talar glide, expressed as a
      proportion of pretreatment deficit, was correlated to the change in weight
      bearing dorsiflexion (r = .88, P<.001), but only after the weight-bearing MWM
      technique. CONCLUSION: This preliminary study demonstrated an initial
      ameliorative effect of MWM treatment techniques on posterior talar glide and
      dorsiflexion range of motion in individuals with recurrent lateral ankle sprain.
      These results suggest that this technique should be considered in rehabilitation
      programs following lateral ankle sprain. This study provides justification for
      follow-up research of the long-term effects of MWM on lateral ankle sprain and
      proposes further work be conducted on the posterior talar glide test.

PMID- 16881464
TI  - Pilates-based therapeutic exercise: effect on subjects with nonspecific chronic
      low back pain and functional disability: a randomized controlled trial.
AB  - STUDY DESIGN: A randomized controlled trial, prestest-posttest design, with a 3-,
      6-, and 12-month follow-up. OBJECTIVES: To investigate the efficacy of a
      therapeutic exercise approach in a population with chronic low back pain (LBP).
      BACKGROUND: Therapeutic approaches developed from the Pilates method are becoming
      increasingly popular; however, there have been no reports on their efficacy.
      METHODS AND MEASURES: Thirty-nine physically active subjects between 20 and 55
      years old with chronic LBP were randomly assigned to 1 of 2 groups. The specific
      exercise-training group participated in a 4-week program consisting of training
      on specialized (Pilates) exercise equipment, while the control group received the
      usual care, defined as consultation with a physician and other specialists and
      healthcare professionals, as necessary. Treatment sessions were designed to train
      the activation of specific muscles thought to stabilize the lumbar-pelvic region.
      Functional disability outcomes were measured with The Roland Morris Disability
      Questionnaire (RMQ/RMDQ-HK) and average pain intensity using a 101-point
      numerical rating scale. RESULTS: There was a significantly lower level of
      functional disability (P = .023) and average pain intensity (P = .002) in the
      specific-exercise-training group than in the control group following the
      treatment intervention period. The posttest adjusted mean in functional
      disability level in the specific-exercise-training group was 2.0 (95% CI, 1.3 to
      2.7) RMQ/RMDQ-HK points compared to a posttest adjusted mean in the control group
      of 3.2 (95% CI, 2.5 to 4.0) RMQ/RMDQ-HK points. The posttest adjusted mean in
      pain intensity in the specific-exercise-training group was 18.3 (95% CI, 11.8 to
      24.8), as compared to 33.9 (95% CI, 26.9 to 41.0) in the control group. Improved
      disability scores in the specific-exercise-training group were maintained for up
      to 12 months following treatment intervention. CONCLUSIONS: The individuals in
      the specific-exercise-training group reported a significant decrease in LBP and
      disability, which was maintained over a 12-month follow-up period. Treatment with
      a modified Pilates-based approach was more efficacious than usual care in a
      population with chronic, unresolved LBP.

PMID- 16881465
TI  - Scapular dysfunction in throwers with pathologic internal impingement.
AB  - STUDY DESIGN: Case control group study. OBJECTIVES: To compare scapular position
      and orientation between baseball players with and without pathologic internal
      impingement. BACKGROUND: Scapular dysfunction has been implicated as a
      contributor to throwing-related pathologic internal impingement of the shoulder
      due to its role in increasing the contact between the greater tuberosity and
      posterior-superior glenoid, thereby impinging the posterior rotator cuff
      tendon(s) and labrum. However, to date, no definitive data demonstrate this
      scapular dysfunction in throwing athletes. The purpose of this study was to
      assess, in a controlled laboratory environment, whether scapular position and
      orientation would be different in throwing athletes diagnosed with pathologic
      internal impingement than in a control group of throwing athletes. METHODS AND
      MEASURES: Eleven throwing athletes diagnosed with pathologic internal
      impingement, using both clinical examination and a magnetic resonance arthrogram,
      were demographically matched with a control group of 11 throwers with no history
      of upper extremity injury. An electromagnetic tracking device was used to measure
      scapular internal/external rotation, anterior/posterior tilt, upward/downward
      rotation, sternoclavicular protraction/retraction, and elevation/depression
      during humeral elevation within the scapular plane. Comparisons were made between
      groups with analysis of variance models (P<.05). RESULTS: The individuals in the
      pathologic internal impingement group demonstrated statistically significant
      increased sternoclavicular elevation when elevating their humerus from 30 degrees
      to 120 degrees (P = .002) and from 60 degrees to 120 degrees (P = .003), compared
      to the control group. Furthermore, these patients also had increased posterior
      scapular tilt position (P = .016). No statistically significant differences were
      present in any other scapular variables measured. CONCLUSIONS: Based on the
      results of this study, throwing athletes diagnosed with pathologic internal
      impingement present with statistically significant increases in sternoclavicular
      elevation and scapular posterior tilt position during humeral elevation in the
      scapular plane.

PMID- 16881466
TI  - Isometric strength of the cervical flexor, extensor, and rotator muscles in 220
      healthy females aged 20 to 59 years.
AB  - STUDY DESIGN: Cross-sectional descriptive study. OBJECTIVES: To determine the
      maximal isometric strength of the flexor, extensor, and rotator muscles of the
      cervical spine in healthy females of working age to document reference values for
      diagnostic and rehabilitation purposes. BACKGROUND: Reference values for the
      isometric strength of the cervical muscles have often been based on small
      samples. To date, reference values for rotator muscles of the cervical spine have
      not been published. METHODS AND MEASURES: The group consisted of 220 volunteer
      healthy females in 4 age groups (20-29 years, n = 57; 30-39 years, n = 51; 40-49
      years, n = 51; 50-59 years, n = 61) from Jyadskyla, Finland. Isometric cervical
      muscle strength in flexion, extension, and rotation was evaluated with a
      specially designed measurement system. RESULTS: Across all age groups, mean (+/
      SD) maximal isometric neck strength was 73.8 +/- 20.0 N in flexion and 190.8 +/-
      31.3 N in extension. Mean (+/-SD) rotation strength was 8.1 +/- 2.3 Nm to the
      right and 7.9 +/- 2.3 Nm to the left. Absolute strength values did not differ
      among the age groups. A weak but significant correlation between body mass and
      neck flexion (r = 0.31, P<.01) and extension (r = 0.25, P<.01) strength was
      found. Intratester reliability varied from 0.87 to 0.96. CONCLUSIONS: Women aged
      20 to 59 years appear to have similar absolute isometric neck muscle strength
      levels. Thus these values can be used as reference for the working-age female
      population.

PMID- 16881467
TI  - Acetabular labral tears of the hip: examination and diagnostic challenges.
AB  - The purpose of this clinical commentary is to provide an evidence-based review of
      the examination process and diagnostic challenges associated with acetabular
      labral tears of the hip. Once considered an uncommon entity, labral tears have
      recently received wider recognition as a source of symptoms and functional
      limitation. Information regarding acetabular labral tears and their association
      to capsular laxity, femoral acetabular impingement (FAI), dysplasia of the
      acetabulum, and chondral lesions is emerging. Physical therapists should
      understand the anatomical structures of the hip and recognize how the clinical
      presentation of labral tears is difficult to view isolated from other hip
      articular pathologies. Clinical examination should consider lumbopelvic and extra
      articular pathologies in addition to intra-articular pathologies when assessing
      for the source of symptoms and functional limitation. If a labral tear is
      suspected, further diagnostic testing may be indicated. Although up-and-coming
      evidence suggests that information obtained from patient history and clinical
      examination can be useful, continued research is warranted to determine the
      diagnostic accuracy of our examination techniques.

PMID- 16881468
TI  - The hip joint: arthroscopic procedures and postoperative rehabilitation.
AB  - Recent technological improvements have resulted in a greater number of surgical
      options available for individuals with hip joint pathology. These options are
      particularly pertinent to the relatively younger and more active population. The
      diagnosis and treatment of acetabular labral tears have become topics of
      particular interest. Improvements in diagnostic capability and surgical
      technology have resulted in an increased number of arthroscopic procedures being
      performed to address acetabular labral tears and associated pathology. Associated
      conditions include capsular laxity, femoral-acetabular impingement, and chondral
      lesions. Arthroscopic techniques include labral tear resection, labral repair,
      capsular modification, osteoplasty, and microfracture procedures. Postoperative
      rehabilitation following arthroscopic procedures of the hip joint carries
      particular concerns regarding range of motion, weight-bearing precautions, and
      initiation of strength activities. Postoperative rehabilitation protocols that
      have been typically used for surgeries such as total hip arthroplasty are often
      not sufficient for the population of patients undergoing arthroscopic procedures
      of the hip joint. Postoperative rehabilitation should be based upon the
      principles of tissue healing as well as individual patient characteristics. As
      arthroscopic procedures to address acetabular labral tears and associated
      pathology evolve, physical therapists have the opportunity to play a significant
      role through the development of corresponding rehabilitation protocols.

PMID- 16881469
TI  - Diagnosis of medial knee pain: atypical stress fracture about the knee joint.
AB  - STUDY DESIGN: Resident's case problem. BACKGROUND: A 19-year-old female,
      currently enrolled in a military training program, sought medical care for a
      twisting injury to her right knee. The patient reported her symptoms as similar
      to an injury she incurred 1 year previously while enrolled in the same military
      program. The patient's past medical history included a nondepressed fracture of
      the medial tibial plateau and complete tear of the deep fibers of the medial
      collateral ligament. DIAGNOSIS: Physical exam revealed nonlocalized anterior and
      medial knee pain without evidence of internal derangement. Initial knee and tibia
      radiographs were unremarkable. Referral for orthopedic physician evaluation
      resulted in concurrence with the therapist's diagnosis and plan of care, and the
      patient was allowed to continue with limited physical training demands. Despite
      periods of rest, the patient's symptoms progressively worsened upon attempts to
      resume running. The examining therapist referred the patient for magnetic
      resonance imaging (MRI) due to the patient's worsening symptoms, normal
      radiographs, and concern for a proximal tibia stress fracture. MRI revealed a
      severe proximal tibial metaphysis stress fracture. DISCUSSION: Stress fractures
      are commonly encountered injuries in individuals subjected to increased physical
      training demands. Early evaluation may not yield well-localized findings and may
      mimic other conditions. Nonmusculoskeletal conditions should be considered in the
      management of patients with stress fractures. This resident's case problem
      illustrates the importance of serial physical examinations and collaboration with
      other healthcare practitioners in the comprehensive assessment and management of
      a patient with a severe stress fracture.

PMID- 16881471
TI  - Protecting the future: attracting interventional radiology trainees--a medical
      student's perspective.

PMID- 16881470
TI  - Survey of gynecologists' and interventional radiologists' opinions of uterine
      fibroid embolization.
AB  - PURPOSE: To evaluate the opinions of gynecologists and interventional
      radiologists regarding uterine fibroid embolization (UFE). METHODS: We mailed
      surveys to all gynecologists and interventional radiologists practising in
      Toronto, Ontario. Study criteria excluded those physicians who did not assess or
      treat patients with uterine fibroids. We evaluated whether they educated patients
      regarding UFE, together with their opinion of current and future effectiveness of
      UFE, self-rated knowledge of fibroid treatment options, and recommendations for
      treatment in several clinical scenarios. RESULTS: A total of 102 gynecologists
      (46.4% response rate) and 28 interventional radiologists (51.9% response rate)
      completed the survey. After applying the exclusion criteria, the final study
      population was 82 gynecologists and 17 interventional radiologists. Both groups
      reported high rates of patient education regarding UFE (gynecologists 100% and
      interventional radiologist 88.2%, P > 0.05). Interventional radiologists had
      higher self-rated knowledge of UFE (P = 0.05), and gynecologists had higher self
      rated knowledge of all other treatment options (P = 0.00). Interventional
      radiologists had a more favourable opinion of the current effectiveness (P <
      0.05) and future use (P > 0.05) of UFE. In 5 of the 7 clinical scenarios,
      interventional radiologists chose UFE, whereas gynecologists chose other
      treatment options (P < 0.05). CONCLUSIONS: Although most gynecologists and
      intterventional radiologists educate their patients regarding UFE as a treatment
      option for uterine fibroids, interventional radiologists have greater self-rated
      knowledge and a higher opinion of current effectiveness and future use and
      recommend UFE more often for uterine fibroid scenarios.

PMID- 16881472
TI  - Radiation dose in abdominal computed tomography: the role of patient size and the
      selection of tube current.
AB  - OBJECTIVE: To develop an algorithm for selecting tube current for computed
      tomography (CT), based on patient weight, that produces abdominal CT images of
      consistent image quality. METHODS: We recorded body weight and radiation exposure
      parameters for 37 patients undergoing abdominal CT. Two radiologists blind to the
      CT technique independently graded 11 measures of image quality, using a 5-point
      (5 = excellent, 4 = good, 3 = acceptable, 2 = poor, and 1 = unacceptable) scale.
      These scores were averaged to generate an overall image quality score. Using
      linear regression, we found a target image noise level that corresponded to an
      overall image quality score of 4.5. We measured CT image noise in 9 uniformly
      attenuating regions of interest in the liver and abdominal aorta. We used linear
      regression to assess the relation between tube current and image noise. A
      prediction equation was developed to set the tube current in different-sized
      patients to produce images at the target noise level. Finally, we calculated the
      dose savings that would have resulted with this tube-current selection technique.
      RESULTS: Image noise was correlated with patient weight (r2 = 0.81). At an
      overall image quality score of 4.5, the noise was 16 HU. Using this target noise
      value, we determined the required tube current for each patient weight and found
      that the use of this technique would have reduced radiation exposure for all
      patients weighing less than 70 kg. The dose reduction for the smallest patient
      (35.4 kg) was 72%. CONCLUSION: To produce CT scans of similar quality, a simple
      prediction equation can be developed for any scanner to optimize radiation dose
      for patients of all body weights.

PMID- 16881473
TI  - Computed tomography and angiographic interventional features of ruptured
      hepatocellular carcinoma: pictorial essay.
AB  - Spontaneous rupture is an uncommon and potentially fatal complication of
      hepatocellular carcinoma (HCC), occurring in approximately 15% of patients with
      HCC in Asia and 3% in the United Kingdom.3 The prognosis for hemorrhage of HCC is
      poor, particularly in those patients with underlying cirrhosis and severe
      coagulopathy. Computed tomography (CT) rather than angiography is the first-line
      modality for the detection of rupture. CT can confirm the diagnosis of ruptured
      HCC and can also help in assessing other organs if the diagnosis is not clear
      prior to imaging. It allows for an assessment of the entire liver, including the
      portal vein, which aids in determining the feasibility of embolization and
      resection. Since the rate of bleeding must normally exceed 1 mL/min before it can
      be detected on angiography and the extravasation of contrast is present in less
      than 20% of cases, CT is a more helpful modality. The optimal CT protocol for
      this condition is triphasic: the precontrast phase allows for assessment of
      ethiodized oil (lipiodol) uptake, the arterial phase demonstrates enhancement of
      the mass, and the portal venous phase allows for assessment of the portal veins.
      Various treatment options have been proposed: transarterial catheter embolization
      (TACE), emergency liver resection, and delayed resection. Surgical treatment is
      difficult, if not impossible. In most cases, rupture is a result of diffuse
      intrahepatic spread of the tumour and underlying liver cirrhosis. Many authors
      have concluded that a multidisciplinary management that includes TACE as the
      primary procedure followed by a delayed resection is the preferred treatment.
      This pictorial essay reviews the radiologic features of spontaneously ruptured
      HCC on CT imaging and of treatment by angiography.

PMID- 16881475
TI  - Factors leading to radiology career selection: results of the 2004 National
      Physician Survey.
AB  - Data from the 2004 National Physician Survey were used to determine when current
      Canadian radiologists made their decision to pursue a radiology career and to
      determine which factors were most influential in their decision. Most respondents
      reported having made this decision during their clerkship years of medical school
      (32.7%) or after a period of time in practice (25.4%). The most influential
      factors involved in this decision were perceived intellectual stimulation and
      workload flexibility or predictability. These results provide insight into the
      trainee's decision to pursue radiology and may be useful to those recruiting for
      radiology as well to medical students considering the field.

PMID- 16881474
TI  - Tolerance of local anesthetic for transrectal ultrasound-guided prostate biopsy:
      our experience and a literature review.
AB  - PURPOSE: To determine whether local anesthetic injection or gel reduced pain
      during transrectal ultrasound-guided prostate biopsies and whether there was
      significant difference between quadrant and apex-only anesthesia. METHODS:
      Between September 2001 and May 2002, 240 male patients with elevated prostate
      specific antigen and (or) abnormal digital rectal examination were randomized
      into 1 of 4 groups: 1) transrectal lidocaine gel, 2) quadrant lidocaine
      injections, 3) apex-only lidocaine injections, or 4) no local anesthetic.
      Patients scored their pain on a numerical rating scale where 0 indicated no pain
      and 10 indicated worst pain. We analyzed mean and standard deviations of scores,
      using a 1-way analysis of variance (ANOVA) and post hoc multiple comparisons with
      Tukey's honestly significant difference (HSD) studentized range test to determine
      whether there were significant differences across the groups. RESULTS: There was
      no significant difference between local anesthetic gel (mean 3.1, SD 1.9) and no
      anesthetic (mean 3.5, SD 1.9) or between quadrant (mean 1.7, SD 1.7) and apex
      only (mean 2.0, SD 1.8) local anesthetic injections. There was significant
      difference between quadrant injections (mean 1.7, SD 1.7) and no local anesthetic
      (mean 3.5, SD 1.9) and between apex-only injections (mean 2.0, SD 1.8) and no
      local anesthetic (mean 3.5, SD 1.9). CONCLUSION: There was significant pain
      reduction with local anesthetic injections but not with gel, and since there was
      no significant difference in efficacy between quadrant and apex-only injections,
      we recommend apex-only local anesthetic injections for transrectal ultrasound-
      guided prostate biopsies because it simplifies the injection procedure.

PMID- 16881476
TI  - Answer to case of the month #109. Retrorectal cystic hamartoma.

PMID- 16881477
TI  - Answer to case of the month #110. Magnetic resonance imaging and spectroscopy in
      Leigh disease.

PMID- 16881480
TI  - IPA develops own software to improve coding under MA.

PMID- 16881479
TI  - Re: December 2005 issue of Canadian Association of Radiologists Journal on breast
      imaging.

PMID- 16881481
TI  - Are docs really shunning managed care? Study says no.

PMID- 16881482
TI  - Impact of HMO penetration on nurse staffing and quality.

PMID- 16881483
TI  - Medicare-oriented plans post lower MA administrative costs.

PMID- 16881484
TI  - Do capitated organizations provide better care for children with chronic
      illnesses?

PMID- 16881485
TI  - An invisible force.

PMID- 16881486
TI  - Like it or not, you are a role model.

PMID- 16881487
TI  - Disposal of epinephrine.

PMID- 16881488
TI  - In answer to the question "Why?".

PMID- 16881489
TI  - Patient safety first: looking back, looking forward.

PMID- 16881490
TI  - Intra-aortic balloon pump therapy--a primer for perioperative nurses.
AB  - The intra-aortic balloon pump (IABP) is a commonly used circulatory-assist device
      that increases myocardial oxygen supply and reduces myocardial oxygen demand,
      thus improving left ventricular function. The inflation and deflation pattern of
      the IABP is the opposite of the heart's rhythm. As the heart rests, the balloon
      inflates, displacing blood volume into the coronary sinus and systemic
      circulation. The balloon deflates just before ventricular ejection, decreasing
      the pressure that the ventricle must eject against. This article describes
      indications and contraindications for use of the IABP, insertion and timing of
      the device, and troubleshooting measures for common malfunctions.

PMID- 16881491
TI  - The modified Bentall procedure for aortic root replacement.
AB  - The Bentall procedure is a surgical repair of an ascending aortic or aortic root
      aneurysm in combination with aortic valve disease. Less commonly, it is used to
      repair aortic dissection affecting the aortic root and valve. During the
      procedure, a composite aortic valve graft is used to replace the proximal
      ascending aorta and aortic valve. The procedure is performed through a median
      sternotomy during cardiopulmonary bypass. In this modification of the original
      procedure, coronary artery circulation is maintained by removing a full-thickness
      "button" of aorta surrounding the coronary ostia, making it easier to implant the
      proximal end of the coronary arteries into openings made in the aortic vascular
      graft.

PMID- 16881493
TI  - Custom cradle trays: secure instrument storage.

PMID- 16881492
TI  - Prevention and early detection of pressure ulcers in patients undergoing cardiac
      surgery.
AB  - Absence of pressure ulcers is increasingly being used as an indicator of quality
      nursing care, based on the premise that pressure ulcers are preventable. This
      retrospective study examined the occurrence, presentation, and timing of pressure
      ulcer development in 150 patients undergoing cardiac surgery. Pressure ulcer
      incidents were recorded in groups of patients who underwent surgery with use of a
      standard foam OR bed mattress; use of a fluid, pressure-reducing OR bed mattress;
      or use of a fluid, pressuring-reducing mattress after a comprehensive educational
      program on pressure ulcer prevention was presented to RNs. Tcers decreased when
      the fluid, pressure-reducing OR bed mattresses were used in conjunction with the
      comprehensive RN education program.

PMID- 16881495
TI  - Now and then: it's all in the Greek.

PMID- 16881496
TI  - Registered children's nurses in emergency departments in England: an exploratory
      survey.
AB  - Recent reports suggest that emergency departments in England are some way from
      achieving universal provision of specific facilities for children and young
      people staffed by practitioners with appropriate qualifications. In 1998, 74 per
      cent of emergency departments employed children's nurses, but only 8 per cent
      employed them in sufficient numbers to provide 24-hour cover (Smith 1998). AIM:
      To establish whether there has been an increase in the number of children's
      nurses employed within emergency departments and to identify their specific roles
      and responsibilities. METHOD: A postal questionnaire was sent to senior managers
      of 99 general emergency departments in England with annual new attendance figures
      of between 45,000 and 100,000. Specific paediatric emergency departments and
      general departments in the London region were excluded. RESULTS: Analysis of data
      from the 52 valid responses suggest that although children comprise around 25 per
      cent of workload, registered children's nurses make up 10 per cent of the
      workforce in general emergency departments. The number employed in each
      department varied from one to 13 whole time equivalents (WTEs), and three
      departments did not employ any at all. In 11 of the 52 departments children's
      nurses were employed to specifically care for children; in other departments
      their main responsibilities were training other staff and developing and
      implementing policies and protocols. Fifty one of the 52 departments employed
      emergency nurse practitioners (ENPs). Children's nurses were employed as ENPs in
      30 of the departments (total 46), a mean of 1.5 WTE per department. A quarter of
      the ENPs who were not registered children's nurses were reported to have received
      no additional training before being deemed competent to assess and treat
      children. CONCLUSION: There has been an increase in the numbers of children's
      nurses employed in general emergency departments but the numbers are still too
      low to comply with policy requirements. Managers should ensure that the skills of
      children's nurses are used to the full, and ENPs need to consider legal and
      accountability issues if they are asked to assess and treat children without
      having accessed appropriate training.

PMID- 16881497
TI  - Family nursing and the management of pain in children.
AB  - Most of the issues around children and pain have been identified and yet
      children's pain continues to be poorly managed. This review aims to take a fresh
      look at this topic through the use of family nursing theory and children's policy
      and rights perspectives. Family nursing and children's policy have a valuable
      contribution to make to assessment issues; nurse education needs to combine
      family-centred care concepts and children's rights in the teaching of pain
      management.

PMID- 16881498
TI  - The highs and lows of learning to be a children's nurse.
AB  - AIM: This study investigates student nurses' perceptions of the process of
      undergoing a programme of education leading to registration as a children's
      nurse. METHOD: Three groups of students (n = 14, 12 and eight) were invited to
      participate in a focus group using the nominal group technique to address the
      following questions: What has helped you in the process of becoming a children's
      nurse? What has hindered you in the process of becoming a children's nurse?
      RESULTS: The factors which helped students most in their quest to become
      children's nurses included: the delivery of specialist lectures from child branch
      nurse lecturers, having good clinical placements with mentors who want to support
      students, and having the support of friends and family. An important factor was
      the desire to become a good children's nurse and wanting to work with children.
      Factors which hindered students included: having unsupportive mentors who
      misjudge student abilities, lack of academic resources including library reading
      materials, too many students in each clinical area and.

PMID- 16881499
TI  - Facing reality: discharge challenges after neuro-rehabilitation.

PMID- 16881500
TI  - Does amethocaine gel influence blood results obtained from capillary sampling?
AB  - In many children routine blood samples are obtained by capillary sampling, a
      technique that appears to cause high levels of pain and distress in the child.
      Topical anaesthesia might alleviate the pain associated with capillary blood
      sampling but would it affect the blood sample? AIM: a preliminary study to
      determine whether topical local anaesthetic would affect the values of commonly
      performed biochemical tests METHOD: 22 healthy adult volunteers were recruited;
      each volunteer acted as his or her own control. Ametop was applied to a socially
      clean digit and covered with an occlusive dressing. After 30 minutes the dressing
      was taken off and excess gel was removed using a cotton wool ball. Two capillary
      samples were obtained from each volunteer, one from the Ametop treated digit and
      one from a digit on the opposing hand. The samples were analysed for sodium,
      potassium, glucose, urea, alkaline phosphatase (ALP), aspartate aminotransferase
      (AST), alinine aminotransferase (ALT) and bilirubin using a Vitros Chemistry
      analyser. Statistical analysis was performed on the blood results using Student's
      paired t-test. RESULTS: Sodium and potassium levels were significantly higher in
      the samples from digits with Ametop applied, and alkaline phosphatase was
      significantly lower. CONCLUSION: The use of amethocaine gel (Ametop) appears to
      affect the results of both sodium and potassium in capillary blood samples and
      therefore it cannot be recommended as a suitable agent for topical anaesthesia
      prior to this procedure.

PMID- 16881501
TI  - Perioperative fasting.

PMID- 16881502
TI  - Using a health promotion model to promote benchmarking.
AB  - The North East (England) Neonatal Benchmarking Group has been established for
      almost a decade and has researched and developed a substantial number of evidence
      based benchmarks. With no firm evidence that these were being used or that there
      was any standardisation of neonatal care throughout the region, the group
      embarked on a programme to review the benchmarks and determine what evidence
      based guidelines were needed to support standardisation. A health promotion
      planning model was used by one subgroup to structure the programme; it enabled
      all members of the sub group to engage in the review process and provided the
      motivation and supporting documentation for implementation of changes in
      practice. The need for a regional guideline development group to complement the
      activity of the benchmarking group is being addressed.

PMID- 16881503
TI  - Short report: refocusing transition clinics.

PMID- 16881504
TI  - The neonatal energy triangle. Part 1: Metabolic adaptation.
AB  - The first part of this two part series on the neonatal energy triangle gives a
      general overview of the transition period during the first six to ten hours of
      life. Although all elements of the triangle, hypothermia, hypoglycaemia and
      hypoxia, are interlinked this first part of the series describes the normal
      metabolic adaptation at birth and the difficulties involved in recognising and
      treating hypoglycaemia. In the second part of the series the two other elements
      of the triangle, hypoxia and hypothermia, will be addressed.

PMID- 16881505
TI  - Human embryonic stem cells: isolation, maintenance, and differentiation.
AB  - The isolation of pluripotent human embryonic stem (hES) cells having the capacity
      to differentiate in vitro to numerous cell types generated much excitement and
      promise in the field of regenerative medicine. However, along with great
      enthusiasm came hot controversy for stem cell research and researchers alike
      because available hES cell lines were isolated from "excess" embryos from in
      vitro fertilization clinics. Despite ethical and political debates, the methods
      and protocols to study diverse lineages are developing. Furthermore, strategies
      using specific growth factor combinations, cell-cell and cell-extracellular
      matrix induction systems are being explored for directed differentiation along a
      desired lineage. However, there is a great need to characterize the mechanisms
      that control self-renewal and differentiation and a necessity to improve
      methodologies and develop new purification protocols for the potential future
      clinical application of hES cells. After the scientific and political obstacles
      are overcome, it is anticipated that the hES cell field will make a tremendous
      difference in conditions, such as burn traumas and diabetic foot ulcers, as well
      a number of degenerative diseases such as Parkinson's disease, type 1 diabetes,
      rheumatoid arthritis, and myocardial infarction. In this introductory chapter, we
      will summarize and review recent progress in the field of hES cell
      differentiation protocols and discuss some of the current issues surrounding hES
      cell research.

PMID- 16881506
TI  - Blastocyst culture for deriving human embryonic stem cells.
AB  - Success in producing a human embryonic stem cell line depends largely on the
      quality of the 5-d-old embryo (blastocyst) used. Such blastocysts are grown from
      frozen-thawed d 1-3 surplus embryos left over from infertility clinics and
      donated for stem cell research with informed patient consent. Knowledge,
      therefore, of the culture conditions and embryo scoring systems that are used to
      generate high-quality blastocysts are crucial. This chapter describes an extended
      microdroplet culture protocol using two-stage sequential culture media with
      morphological and polarized optical parameters for embryo scoring for each day of
      embryonic growth to help produce high-quality blastocysts.

PMID- 16881507
TI  - Propagation of human embryonic stem cells on human feeder cells.
AB  - Human embryonic stem (hES) cell lines are usually derived and propagated on
      inactivated murine embryonic fibroblast (MEF) feeders. The use of MEFs and
      culture ingredients of animal origin for hES cell support increases the risk of
      cross-contamination of the hES cells with infectious animal agents from the MEFs
      and animal-based culture medium. This thus makes such hES cells lines undesirable
      for clinical application. This chapter describes several protocols used in the
      propagation of hES cells on human fibroblast feeder cells. Two culture methods,
      the bulk enzymatic culture protocol and the microdissection "cut and paste"
      protocol are described. Only certain human fetal and adult fibroblast feeders
      support hES cell growth. Methods for the characterization of pluripotent
      undifferentiated hES cells grown on human feeders including cell surface marker
      staining and real-time polymerase chain reaction are also described.

PMID- 16881508
TI  - Derivation and maintenance of human embryonic stem cells.
AB  - Since their derivation in 1998, human embryonic stem cells (hESCs) have been the
      center of tremendous scientific efforts in improve the existing methodologies for
      their isolation and maintenance to exhaust the potential use of these unique
      cells in cell-based therapy and developmental research. To date, there are more
      than 50 reported well-characterized hESC lines worldwide. hESCs are traditionally
      isolated from the blastocysts on mouse embryonic fibroblasts. The most used
      method for isolating the inner cell mass from the human blastocyst is
      immunosurgery. This chapter focuses on the basic methods for the derivation and
      maintenance of hESC lines.

PMID- 16881509
TI  - Isolation and characterization of human embryonic stem cells.
AB  - The derivation of human embryonic stem (hES) cells is a challenging procedure.
      The isolation and maintenance of hES is visually and manually complicated,
      involving mechanical or enzymatic passaging using either collagenase or trypsin.
      This chapter describes detailed protocols that have been used for the derivation,
      maintenance, and characterization of hES cells in vitro along with protocols to
      test their differentiation potential in vivo. When used as a guideline, these
      protocols will assist researchers in setting up a hES cell laboratory.

PMID- 16881510
TI  - Routine culture and differentiation of human embryonic stem cells.
AB  - Human embryonic stem cells provide both an in vitro model of human development
      and a potential source of cells for treatment of degenerative, metabolic, or
      traumatic disorders. This chapter describes techniques for routine maintenance
      and differentiation of human embryonic stem cells in culture.

PMID- 16881511
TI  - Culture of human embryonic stem cells on human and mouse feeder cells.
AB  - This chapter describes the methods we use to maintain and expand undifferentiated
      human embryonic stem (hES) cells on human and mouse feeder cells. All of the
      available hES cells have been derived and propagated on primary mouse embryonic
      fibroblasts as feeder cells that have been mitotically inactivated. We found that
      hES cells can be successfully cultured on selected human feeder cells, such as
      marrow stromal cells derived from adult bone marrow and breast skin fibroblasts.
      Detailed protocols to use human and mouse feeder cells are described here,
      together with our method to split hES cells by trypsin/ethylenediaminetetraacetic
      acid-mediated dissociation. We also describe methods we use to characterize hES
      cells expanded on either human or mouse feeder cells, including alkaline
      phosphatase staining, immunostaining for cell-surface markers associated with
      undifferentiated hES cells, and teratoma formation in mice.

PMID- 16881512
TI  - Maintenance of human embryonic stem cells in animal serum- and feeder layer-free
      culture conditions.
AB  - The availability of human embryonic stem cells (hESCs) reflects their outstanding
      potential for research areas such as human developmental biology, teratology, and
      cell-based therapies. To allow their continuous growth as undifferentiated cells,
      isolation and culturing were traditionally conducted on mouse embryonic
      fibroblast feeder layers, using medium supplemented with fetal bovine serum.
      However, these conditions allow possible exposure of the cells to animal
      pathogens. Because both research and future clinical application require an
      animal-free and well-defined culture system for hESCs, these conventional
      conditions would prevent the use of hESCs in human therapy. This chapter
      describes optional culture conditions based on either animal-free or feeder-free
      culture methods for hESCs.

PMID- 16881513
TI  - Manipulation of self-renewal in human embryonic stem cells through a novel
      pharmacological GSK-3 inhibitor.
AB  - This chapter introduces a new method of maintaining human embryonic stem cells
      (hESCs) in the undifferentiated state through treatment with a GSK-3 inhibitor,
      BIO, under a feeder-free condition. Additionally, methods are introduced that
      determine multidifferentiation potential of hESCs by differentiating into a
      specific type or random heterogenous cell populations in vitro. These approaches
      will become a fundamental platform to identify molecular networks regulating cell
      fate determination in hESCs and mouse embryonic stem cells.

PMID- 16881514
TI  - Derivation of human feeders for prolonged support of human embryonic stem cells.
AB  - Human embryonic stem (hES) cell lines are derived and propagated using animal
      based feeder cells and xenoproteins. Reliance on a xenosupport system introduces
      many disadvantages with respect to exploiting the therapeutic potential of hES
      cells because of the risk of transmission of pathogens from the animal feeders to
      hES cells. Recently, human feeders (commercial and in-house derived) in the
      presence of human-based culture ingredients have been successfully used to derive
      and propagate xeno-free hES cell lines. In-house-derived human feeders, however,
      have the advantage over commercial feeders of not being previously exposed to
      xeno-proteins. This chapter describes the collection of human tissue biopsies and
      the establishment of human feeder monolayers for the derivation and support of
      hES cell lines in the presence of human-based culture ingredients.

PMID- 16881515
TI  - Transplantation of human embryonic stem cells to the chick embryo.
AB  - The traditional methods of studying the differentiation of human embryonic stem
      cells (hESCs) are to differentiate them in vitro or in immune-deficient mice as
      teratomas. The chick embryo is a well-studied and accessible experimental system
      that has been shown to permit the development of mammalian cells, including
      murine embryonic stem cells. We therefore performed experiments transplanting
      colonies of hESCs into organogenesis-stage chick embryos, hoping this might
      provide a novel system for studying the developmental programs and decisions of
      these important cells. hESCs, constitutively expressing green fluorescent protein
      or labeled with the dye CFDA, were used to allow the following the hESC in living
      embryos. As a first step, we chose to transplant hESCs into the trunk of chick
      embryos, both into and instead of developing somites. Our first results showed
      that hESCs survive, migrate, and integrate into the tissues of the chick embryo.
      Some of the hESCs differentiate and the type of embryonic microenvironment that
      the implanted cells were exposed to modified their differentiation. Therefore,
      this hESC-chick embryo system has potential for complementing studies in rodents
      and in vitro, and uniquely, to shed light on early processes in the development
      of human cells in the embryonic context.

PMID- 16881516
TI  - Derivation and characterization of neuronal precursors and dopaminergic neurons
      from human embryonic stem cells in vitro.
AB  - Dopaminergic neurons of human origin have many potential research applications
      such as in vitro studies on biochemical pathways related to neuronal disorders,
      and potentially direct cell replacement for therapeutic use. Dopaminergic neurons
      with apparently normal properties can be produced from embryonic stem cells from
      mice and sub-human primates by the simple procedure of coculturing with the PA6
      stromal cell line. Recently, we have demonstrated that this coculture system can
      induce dopaminergic differentiation in human embryonic stem cells, and the human
      embryonic stem cell-derived dopaminergic cells exhibit biochemical and functional
      properties of mature dopaminergic neurons.

PMID- 16881517
TI  - In vitro differentiation of neural precursors from human embryonic stem cells.
AB  - We describe a procedure for efficient and reproducible differentiation of
      neuroectodermal cells from human embryonic stem (ES) cells using an adherent
      colony culture. ES cell colonies are detached intact from the fibroblast feeder
      layer using dispase or collagenase. The ES cell aggregates, after 4-6 d in
      suspension culture, are adhered to the culture surface and form colonies of
      monolayer in a chemically defined medium. Under this culture condition, columnar
      neuroectodermal cells appear in the center of each colony and organize into
      neural tube-like rosettes after 14 d of differentiation culture. These
      neuroectodermal cells in the rosettes can be effectively isolated through
      differential enzymatic and adhesion treatment and the neural population accounts
      for at least 70% of the total differentiated progenies. Thus, our system not only
      provides a source of synchronized neuroectodermal cells, but also offers a
      paradigm to dissect mechanisms of neural induction and cell lineage specification
      during early human development.

PMID- 16881518
TI  - Derivation and characterization of hematopoietic cells from human embryonic stem
      cells.
AB  - In vitro, the aggregation of pluripotent human embryonic stem cells (hESC) into
      cell clusters termed embryoid bodies (EB) allows for the spontaneous
      differentiation of hESC into progeny representing endoderm, mesoderm, and
      ectoderm lineages. During human EB (hEB) differentiation, stochastic emergence of
      hematopoietic cells can be enhanced by a combination of hematopoietic cytokines
      and the ventral mesoderm inducer bone morphogenetic protein (BMP)-4. Dependent on
      the presence of hematopoietic cytokines and BMP-4, vascular endothelial growth
      factor (VEGF-A165) selectively promotes erythropoietic development toward the
      primitive lineage. The effects of VEGF-A165 can be augmented by erythropoietin
      (EPO). Hematopoietic cells are derived from a rare subpopulation of hemogenic
      precursors during hEB development. These hemogenic precursors lack CD45, but
      express PECAM-1, Flk-1, and VE-cadherin (hereinafter CD45(neg)PFV) and are solely
      responsible for hematopoietic cell fate. Human ESC-derived hematopoietic cells
      have similar colony and cellular morphologies to those derived from committed
      adult hematopoietic tissues, and also show repopulating capacity in immune
      deficient mice after intrabone marrow transplantation. In this chapter, we
      describe methods that have been successfully applied in our laboratory, including
      (1) generation of hematopoietic cells by EB formation; (2) augmentation of
      hematopoiesis by use of hematopoietic cytokines and BMP-4; (3) promotion of
      erythropoietic development by addition of VEGF-A165 and EPO; (4) isolation of
      CD45(neg)PFV hemogenic precursors and generation of hematopoietic cells from
      these precursors; and (5) characterization of hESC-derived hematopoietic cells in
      vitro and in vivo.

PMID- 16881520
TI  - Genetic manipulation of human embryonic stem cells by transfection.
AB  - One of the great advantages of embryonic stem (ES) cells over other cell types is
      their accessibility to genetic manipulation. They can easily undergo genetic
      modifications while remaining pluripotent, and can be selectively propagated,
      allowing the clonal expansion of genetically altered cells in culture. Since the
      first isolation of ES cells in mice, many effective techniques have been
      developed for gene delivery and manipulation of ES cells. These include
      transfection, electroporation, and infection protocols, as well as different
      approaches for inserting, deleting, or changing the expression of genes. These
      methods proved to be extremely useful in mouse ES cells, for monitoring and
      directing differentiation, discovering unknown genes and studying their function,
      and are now being initiated in human ES (hES) cells. This chapter describes the
      different approaches and methodologies that have been applied for the genetic
      manipulation of hES cells and their applications. Specifically, two detailed
      protocols that can be used to generate clones of genetically modified hES cells
      by transfection will be described, with special emphasis on the important
      technical details that are required for this purpose.

PMID- 16881519
TI  - Retroviral transduction of hematopoietic progenitors derived from human embryonic
      stem cells.
AB  - It has been recently identified that cytokines and BMP-4 promote hematopoiesis
      from human embryonic stem cells (hESC) and that, before hematopoietic commitment,
      a rare subpopulation of cells lacking CD45, but expressing PECAM-1, Flk-1, and VE
      cadherin (hereinafter termed CD45(neg)PFV precursors), are exclusively
      responsible for hematopoietic cell fate on cytokine stimulation. Efficient
      strategies to stably transduce these hematopoietic precursors specifically
      generated from hESCs would provide a novel and desirable tool to study
      hematopoietic development through the introduction and characterization of
      candidate genes suspected to regulate self-renewal processes of hESC-derived
      hematopoietic cells or dynamically track hESC-derived hematopoietic stem cells in
      vivo. To date, only transient transfection and stable transduction using
      lentiviral vectors have been reported in undifferentiated hESC followed by random
      and spontaneous differentiation into different cell types. However, protocols for
      stable transduction of hematopoietic progenitors prospectively derived from hESC
      need to be developed yet. In the present chapter, we described detailed methods
      on the recently characterized and optimized GALV-pseudotyped retroviral gene
      transfer strategy to stably transduce the hematopoietic progenitor cells
      prospectively derived from CD45(neg)PFV hemogenic precursors as a vital tool to
      study hematopoietic development and to characterize candidate genes suspected to
      eventually confer robust and sustained repopulating ability to hESC-derived
      hematopoietic cells.

PMID- 16881521
TI  - Designing, testing, and validating a microarray for stem cell characterization.
AB  - Microarray technology is a powerful tool that allows for simultaneous assessment
      of the expression of thousands of genes and identification of gene expression
      patterns associated with specific cell types. Here we describe a protocol using
      this method to examine stem cells.

PMID- 16881522
TI  - Microarray approach to identify the signaling network responsible for self
      renewal of human embryonic stem cells.
AB  - This chapter introduces the representative method to culture human embryonic stem
      cells (hESCs) under the feeder and feeder-free conditions, the former of which is
      used to maintain or expand undifferentiated hESCs, and the latter can be used for
      preparation of pure hESCs RNA samples, or for screening factors influential on
      self-renewal of hESCs. Also described in this chapter: a protocol and tips for
      conducting gene chip analysis focusing on widely used Affymetrix microarrays.
      These techniques will provide an unprecedented scale of biological information to
      illuminate a key to decipher complex signaling networks controlling pluripotency.

PMID- 16881523
TI  - Massively parallel signature sequencing.
AB  - Massively parallel signature sequencing is an ultra-high throughput sequencing
      technology. It can simultaneously sequence millions of sequence tags, and,
      therefore, is ideal for whole genome analysis. When applied to expression
      profiling, it reveals almost every transcript in the sample and provides its
      accurate expression level. This chapter describes the technology and its
      application in establishing stem cell transcriptome databases.

PMID- 16881524
TI  - Confrontation cultures of embryonic stem cells with multicellular tumor spheroids
      to study tumor-induced angiogenesis.
AB  - Human embryonic stem cells efficiently differentiate blood vessels, which allows
      using this in vitro model to study the interaction of blood vessels with adjacent
      tissues. Herein, we introduce confrontation cultures of human embryonic stem
      cells with multicellular tumor spheroids to investigate molecular mechanisms of
      tumor-induced angiogenesis. Vascularization of tumor tissue by the host is a
      prerequisite for tumor growth, which has led to the development of antiangiogenic
      therapy. This promising anti-cancer therapy intends to reduce, halt, or even
      regress tumor growth by deprivation from blood, oxygen, and nutrient supply.
      Confrontation cultures of human embryonic stem cells with multicellular tumor
      spheroids allow the investigation of the time course of endothelial cell invasion
      into the tumor tissue, the concomitant analysis of changes in angiogenesis
      related gene expression, and analysis of the cellular microenvironment (i.e.,
      pericellular oxygen pressure, tissue pH, and levels of tissue reactive oxygen
      species). The in vitro model of confrontation cultures is suitable for routine
      screening of antiangiogenic agents in pre-clinical trials and may be used to
      replace animal experiments applied in antiangiogenesis research.

PMID- 16881525
TI  - A novel experimental platform for investigating cancer growth and anti-cancer
      therapy in a human tissue microenvironment derived from human embryonic stem
      cells.
AB  - There is no available experimental system wherein human cancer cells can be grown
      in the context of a mixed population of normal differentiated human cells for
      testing biological aspects of cancer cell growth (tumor cell invasion,
      angiogenesis) or response to anti-cancer therapies. Human embryonic stem cells
      when implanted into immunocompromised mice develop teratomas containing complex
      structures, comprising differentiated cell types representing the major germline
      derived lineages. We sought to determine whether human cancer cells would grow
      within such teratomas and display properties associated with malignancy such as
      invasiveness and recruitment of blood vessels. Ovarian cancer cells (HEY), stably
      expressing an H2A-GFP fusion protein, which allows tracking of tumor cells, were
      injected into mature teratomas and developed into tumors. The growth,
      proliferation capacity, invasion, and induction of blood vessel formation were
      examined. We propose using the novel experimental platform we have described,
      consisting of human tumor cells growing within a human cellular microenvironment
      derived from human embryonic stem cells, to develop a preclinical model for
      investigating and manipulating the stromal response in tumor cell growth, as an
      additional tool in cancer research.

PMID- 16881526
TI  - The analysis of mitochondria and mitochondrial DNA in human embryonic stem cells.
AB  - As human embryonic stem cells (hESCs) undergo differentiation, they express genes
      characteristic of the lineage for which they are destined. However, fully
      differentiated individual cell types can be characterized by the number of
      mitochondria they possess and the copies of the mitochondrial genome per
      mitochondrion. These characteristics are indicative of a specific cell's
      requirement for adenosine triphosphate (ATP) and therefore cellular viability and
      function. Consequently, failure for an ESC to possess the full complement of
      mitochondria and mitochondrial DNA (mtDNA) could limit its final commitment to a
      particular fate. We describe a series of protocols that analyze the process of
      cellular mitochondrial and mtDNA differentiation during hESC differentiation. In
      addition, mtDNA transcription and replication are key events in cellular
      differentiation that require interaction between the nucleus and the
      mitochondrion. To this extent, we describe a series of protocols that analyze the
      initiation of these key events as hESCs progress from their undifferentiated
      state to the fully committed cell. Last, we describe real-time polymerase chain
      reaction protocols that allow both the identification of mtDNA copy number and
      determine whether mtDNA copy is uniform (homoplasmy) in its transmission or
      heterogeneous (heteroplasmy).

PMID- 16881527
TI  - [Legal and practical issues regarding collection and disclosure of prognostic
      data in population-based cancer registries].

PMID- 16881528
TI  - [Epidemiology, treatment and prevention of attention deficit/hyperactivity
      disorder: a review].
AB  - Attention deficit/hyperactivity disorder (ADHD) is characterized by
      inattentiveness and/or impulsiveness and hyperactivity, which are unsuited for
      the developmental stage or age. Although mechanisms leading to the onset of the
      disease are unclear, this condition seriously hinders childrens' social or
      learning functions, and recently it was selected as a target disease for a
      special supporting education program by the Minitry of Education, Culture,
      Sports, Science and Technology, together with learning disorders and high
      functioning pervasive developmental disorders in Japan. In spite of the
      increasing social interest in ADHD, the epidemiological evidence including data
      for incidence, prevalence, gender differences, and etiology remain insufficient.
      In Western countries, as represented by the United States, operational diagnostic
      criteria such as DSM-IV are widely used and several diagnostic processes using
      structured interviews have been established. However, the diagnostic criteria
      have not been consistent even within DSM as shown by DSM-IV and DSM-III-R, and
      therefore basic epidemiological evidence was not consistent in the previous
      studies. Regarding the etiology of ADHD, exposure to addictive substances during
      the pregnancy period caused by maternal smoking or drinking, and familial
      socioeconomic status are considered important environmental factors. In addition,
      a family history of mental disorders and polymorphisms of dopamine-related genes
      such as DRD4 or SLC6A3 have been noted as genetic factors concerning the
      development of ADHD. However, in Japan, no studies of these subjects or gene
      environment interactions have so far been performed. Thus, epidemiological
      assessment of other than Western populations is needed. In the clinical
      situation, it is important to grasp the timing of treatment and target problems
      on the basis of changes of children's ability to control their attention or
      behavior, and environmental factors associated with growth processes. Especially,
      comorbidity such as conduct disorder or oppositional defiant disorder is a
      critical problem. Thus, considering that ADHD is a multifactorial disease, a
      comprehensive therapic strategy involving medication, education, judicature, and
      administration should be established for primary and secondary prevention.

PMID- 16881529
TI  - [Active life expectancy for elderly Japanese by chewing ability].
AB  - OBJECTIVE: Panel interview surveys of nationally representative elderly people
      aged 65 years or above in Japan were conducted three times at 2-year intervals
      since 1999 (Nihon University Japanese Longitudinal Study of Aging) to estimate
      health expectancy for males and females separately according to their chewing
      ability. METHOD: Multistate life table methods were applied to estimate health
      expectancy. Three health states, namely, active, inactive and dead, were defined
      according to the ability to perform specified daily activities. Living
      respondents were considered to be in an "inactive state" if they responded "very
      difficult" or "unable" for performance of at least one ADL or IADL. Otherwise
      they were considered to be in an "active state". 4,323 sampled persons who
      responded to the baseline survey were included in the study. Based on estimated
      transition probabilities over the survey period between active and inactive
      states, and active and inactive states to death, both population- and status
      based multistate life tables were constructed according to chewing ability. Those
      who could chew relatively hard foods at the baseline survey were classified as
      Group A and those who could chew only relatively soft foods were classified as
      Group B. RESULTS: The population-based multistate life tables indicated that at
      age 65, total life expectancy was 19.3/23.2 (males/females) years for Group A and
      16.7/21.1 years for Group B. Active life expectancy was 16.8/18.6 years and
      13.6/16.3 years, and inactive life expectancy was 2.4/4.6 years and 3.1/4.8 years
      for Groups A and B respectively. A statistically significant difference was
      observed between the two groups only in terms of active life expectancy. From
      status-based multistate life tables, similar patterns were observed for those
      whose status at the baseline was "active". CONCLUSION: These results suggest that
      maintenance or recovery of sufficient chewing ability for elderly people is
      related to a longer total life expectancy and even more strongly related to a
      longer active life expectancy.

PMID- 16881530
TI  - [The present situation regarding research into a certain electronic support group
      that aims to heal grief].

PMID- 16881531
TI  - [A preventive strategy for hepatitis C infection in Kobe City. Official
      announcement of medical facilities with past fibrinogen administration].

PMID- 16881532
TI  - [Estimates of active life expectancy based on the data of the public nursing-care
      insurance in Mie prefecture].

PMID- 16881533
TI  - [Analysis of an adult measles outbreak in the eastern part of Ehime prefecture in
      Japan].
AB  - PURPOSE: An outbreak of adult measles occurring in the eastern part of Ehime
      prefecture in Japan was analyzed, and the future directions of measures against
      infectious diseases in public health centers was studied. METHOD: An outbreak of
      adult measles (in individuals more than 18 years old) occurred in the eastern
      part of Ehime prefecture between October 2002 and July 2003. During this
      outbreak, provisional surveillance of adult measles as well as pediatric measles
      (less than 18 years old) was performed by all clinics and hospitals in addition
      to that by The Ehime Epidemiological Surveillance of Infectious Diseases
      (sentinel surveillance). Furthermore, identification of viral genes was performed
      from pediatric and adult measles patient samples. RESULTS: 112 cases of measles
      in adults and 200 cases in children were reported in Ehime between October 2002
      and July 2003, and the rates for the eastern part of the prefecture accounted for
      89.7% and 94.1% respectively. The relation between the pediatric measles and
      adult measles could be followed by change in the outbreak number of patients week
      by week. The genotype of the measles viruses isolated was type H1, which is
      prevalent in China and Korea. The results of an epidemiological survey showed
      that 59.3% of adult and 84.1% of pediatric cases had not been vaccinated. The
      measles vaccination rates for adult and pediatric cases were 21.9% and 11.4%,
      respectively. While the number of measles cases detected by sentinel pediatric
      surveillance comprised 32.0% of the measles cases reported by all pediatricians,
      the figure for adult measles cases was only 11.6% of those reported by all
      clinics and hospitals. CONCLUSIONS: It was suggested that improvement in the
      vaccination rates and revaccination rates mainly among school children or young
      people is necessary to prevent measles outbreaks. The surveillance system must be
      strengthened to increase the number of sentinel hospitals because an outbreak may
      not be detected with the current approach, especially for measles among adults.
      Positive information exchange between public health centers and medical
      institutions also appear to be particularly important.

PMID- 16881535
TI  - The physiologic basis for the management of ventricular assist devices.
AB  - Mechanical ventricular assist devices are now approved as destination therapy for
      terminal heart failure. It is the purpose of this review to discuss the
      physiology of this technology that is considered in outpatient care. The
      currently available pulsatile devices are solely dependent of preload volume and,
      when placed in the automatic mode, can maintain physiologic cardiac outputs with
      exercise. However, because of their dependence on preload volume, there are
      unique physiologic consequences; device bradycardia represents volume depletion,
      device tachycardia reflects volume overload. The differential diagnosis of left
      ventricular assist device dysfunction includes native right ventricular failure,
      native left ventricular recovery, or other technical considerations. The
      management of biventricular mechanical support as well as arrhythmia management
      and the role of echocardiographic assessment in this unique patient population
      will be discussed. Expertise in outpatient management of such devices is now a
      requisite for subspecialists in heart failure, In the future, technical
      innovations may simplify management for professionals, patients, and their
      families.

PMID- 16881534
TI  - Pregnancy and prosthetic atrioventricular valve thrombosis.

PMID- 16881536
TI  - Coronary arterial revascularization: past, present, future: part I--historical
      trials.
AB  - Advances in coronary artery revascularization have been accompanied by clinical
      trials evaluating these advances. From the Coronary Artery Surgery Study and
      Bypass Angioplasty Revascularization Investigation to the more recent Arterial
      Revascularization Therapy Study (ARTS1) and the Medicine, Angioplasty, or Surgery
      Study (MASS2), these clinical trials provide us with a rationale for the way we
      conduct clinical practice. This paper reviews the data supporting historical
      revascularization strategies for our patients, including medical therapy,
      angioplasty, and bare metal stents. Several recurrent themes emerge. These
      include a need for increased revascularization in patients who undergo
      percutaneous treatments, the durability of surgical arterial revascularization,
      and the importance of medical therapy as the mainstay of treatment. Part II will
      address newer therapies.

PMID- 16881538
TI  - Association between Pro12Ala polymorphism of peroxisome proliferator-activated
      receptor-gamma 2 and myocardial infarction in the Chinese Han population.
AB  - BACKGROUND: Peroxisome proliferator-activated receptor-gamma 2 (PPAR-gamma 2) is
      a nuclear receptor that plays an important role in adipocyte differentiation,
      energy metabolism, and homeostasis. The Pro12Ala polymorphism of PPAR-gamma 2 is
      associated with decreased risk of diabetes mellitus. Presumably, it may have a
      protective effect on myocardial infarction (MI). HYPOTHESIS: The purpose of the
      study was to explore the association between the Pro12Ala polymorphism and the
      risk of MI in the Chinese population. METHODS: The Pro12Ala polymorphism was
      detected by polymerase chain reaction-restriction fragment length polymorphism
      among 844 subjects, including 218 patients with MI and 626 controls. Clinical
      parameters such as fasting serum total cholesterol, triglycerides, and plasma
      glucose were detected by autoanalyzer assay. Waist circumference, weight, height,
      and blood pressure (BP) were measured and body mass index (BMI) was calculated.
      RESULTS: The frequencies of the Ala allele in the MI and control groups were
      0.053 and 0.032, respectively. There was a significant difference in genotype and
      allele frequency distribution between the two groups (after adjustment for age,
      gender, BP, fasting plasma glucose, total cholesterol, triglycerides, and
      smoking, odds ratio [OR] = 2.51, 95% confidence interval [CI]: 1.26-5.00, p =
      0.009). In the group with MI, the difference in frequency of the Ala allele in
      women (0.241) compared with that of men (0.056) was significant (OR = 4.29, 95%
      CI: 1.96-9.37, p < 0.001). There was no relationship between the Pro12Ala
      polymorphism and waist circumference, weight, BMI, BP, or triglycerides (p >
      0.05). CONCLUSIONS: Our study suggests that Pro12Ala polymorphism is associated
      with increased risk of MI.

PMID- 16881539
TI  - Role of angiographic coronary artery collaterals in transient ischemic left
      ventricular cavity dilatation during stress echocardiography.
AB  - BACKGROUND: The role of coronary artery collaterals in transient ischemic left
      ventricular (LV) dilatation (TID) during stress echocardiography is not well
      defined. HYPOTHESIS: Transient ischemic LV dilatation is a marker for extensive
      and severe coronary artery disease and represents patients without good
      collaterals. METHODS: We evaluated 212 consecutive patients (57 +/- 16 years, 70%
      male) who had coronary angiography and stress echocardiography within a 3-month
      period. This cohort of patients was divided into three groups based on type of
      collaterals: Group A: no collaterals; Group B: collaterals supplied by vessels
      without flow-limiting stenosis (good collaterals); Group C: collaterals supplied
      by vessels with flow-limiting stenosis (bad/jeopardized collaterals). In all
      patients, angiographic jeopardy score (AJS), ejection fraction (EF), and wall
      motion score index (WMSI) at rest and during stress were evaluated. Transient
      ischemic LV dilatation was defined as transient increase in the end-systolic
      dimensions from rest to peak stress. RESULTS: Transient ischemic LV dilatation
      was present in 42 (20%) patients. Patients with TID had a lower EF, higher AJS,
      greater number of ischemic segments, and higher peak WMSI. Patients with TID in
      Group A (no collaterals) and Group C (jeopardized collaterals) had a greater
      percentage of multivessel disease than those in Group B (good collaterals).
      Presence of Group A or Group C collaterals was a predictor of TID even after
      controlling for multivessel disease, rest and peak WMSI, and left anterior
      descending artery disease. CONCLUSIONS: Transient ischemic LV dilatation on
      stress echocardiography is a marker for extensive and severe coronary artery
      disease and represents patients with angiographically absent collaterals or those
      with jeopardized coronary collaterals.

PMID- 16881537
TI  - Prevalence of amiodarone-related hepatotoxicity in 720 Chinese patients with or
      without baseline liver dysfunction.
AB  - BACKGROUND: The prevalence of hepatotoxicity after longterm oral amiodarone
      therapy in Chinese patients with or without elevated liver enzymes at baseline is
      unknown. HYPOTHESIS: Amiodarone may still be safely prescribed for Chinese
      patients who have baseline liver dysfunction. METHODS: This is a retrospective
      cross-sectional study. Significant liver dysfunction (SLD) was defined as alanine
      aminotransferase (ALT) > 2 times upper limit of normal range. RESULTS: Baseline
      liver function was checked in 628 of the 720 Chinese patients identified. The
      mean duration of amiodarone use was 615.9 +/- 703.1 days. Ninety patients (14.3%)
      had elevated baseline ALT. The prevalence of SLD was 3.7% (confidence interval
      [CI] 2.1-5.3%) and 4.4% (CI 0.2-8.6%) in patients with normal (n = 538) and
      elevated (n = 90) baseline ALT, respectively (p = 0.765). Therapy was continued
      in 42 patients with elevated baseline ALT until final follow-up. Eight of these
      (19.0%) had elevated ALT upon final follow-up, but the derangement was mild (mean
      ALT 134.8 +/- 145.9 IU/l, median 76 IU/l). During follow up, 24 patients
      developed SLD and half of these subsequently withdrew from therapy. The ALT
      levels at final follow-up had improved over time in both groups, but the mean
      difference was not significant (255.1 +/- 706.4 vs. 131.0 +/- 207.5 IU/l, p =
      0.312). CONCLUSION: The prevalence of SLD in Chinese patients taking oral
      amiodarone with or without elevated baseline ALT was similar (4.4 vs. 3.7%). It
      seems that amiodarone may be safely prescribed in patients with elevated baseline
      ALT.

PMID- 16881541
TI  - Cardiac event rate in a lifestyle modification program for patients with chronic
      coronary artery disease.
AB  - BACKGROUND: Several clinical trials have shown that intensive lifestyle
      modification programs have a significant impact on cardiovascular risk factors.
      HYPOTHESIS: This paper is a retrospective analysis to determine the effect of
      participation in a 2-year lifestyle management program on long-term clinical
      outcome in patients outside the setting of a clinical trial. METHODS: Patients
      with angiographically confirmed coronary artery disease (CAD) enrolled in a 2
      year program of exercise training, dietary counseling, stress management, and
      therapeutic education. They were accepted into the program from 1991 through
      December 2002. Follow-up after completion of the program ranged from 10 to 2
      years. RESULTS: In all, 134 patients enrolled in the program; of these, 77
      completed the program and 57 failed to do so. Those who completed the program
      improved their effort tolerance and reached recommended goals for serum lipid and
      blood pressure levels. The cumulative event rate (cardiac death, myocardial
      infarction, and stroke) over 10 years in the patients who completed the program
      was 1.5%. The corresponding event rate in patients who dropped out was 18% (p <
      0.02). CONCLUSIONS: It is suggested that patients who complete a 2-year lifestyle
      modification program appear to have a favorable prognosis over an extended period
      of time.

PMID- 16881540
TI  - Effect of cardiopulmonary bypass on cytokine network and myocardial cytokine
      production.
AB  - BACKGROUND: In addition to the well-investigated proinflammatory cytokine
      expression, there is an ever increasing interest in the field of anti
      inflammatory response to cardiopulmonary bypass (CPB). Evidence suggests that
      myocardium serves as an important source of cytokines during reperfusion and
      application of CPB. The effect of coronary artery bypass graft (CABG) without CPB
      on myocardial cytokine production has not as yet been investigated. HYPOTHESIS:
      Cardiopulmonary bypass can cause long-term disturbance in pro- and anti
      inflammatory cytokine balance, which may impede a patient's recovery following
      surgery. Therefore, the effect of CPB on the balance of the pro-/anti
      inflammatory cytokines network and myocardial cytokine outflow was assessed
      throughout a longer period after surgery. METHODS: Twenty patients were scheduled
      for CABG with CPB and 10 had off-pump surgery. Blood samples were taken before,
      during, and over the first week following surgery. Coronary sinus blood samples
      were collected during surgery. The ratio of pro- and anti-inflammatory cytokines
      was calculated and the cytokine concentration of peripheral and coronary sinus
      blood were compared in both groups. RESULTS: Pro-/anti-inflammatory cytokine
      ratio decreased early after CPB followed by a delayed and marked increase. A more
      balanced ratio was present following off-pump surgery. Coronary sinus levels of
      certain cytokines exceeded the concentration of systemic blood in the course of
      CPB but not during off-pump operation. CONCLUSION: Patients show pro-inflammatory
      predominant cytokine balance at a later stage after CPB in contrast to those
      without CPB. The heart produces a remarkable amount of cytokines only in the
      course of surgery with CPB.

PMID- 16881542
TI  - Thrombolysis in ST-segment elevation myocardial infarction: potential role of
      thin-slice computed tomography in the assessment of reperfusion and plaque
      characterization.

PMID- 16881543
TI  - Metastatic infiltration of the myocardium presenting with angina pectoris.

PMID- 16881544
TI  - Supraventricular tachycardia in Wolff-Parkinson-White syndrome: to and fro.

PMID- 16881545
TI  - Elevations of troponin in patients with epileptic seizures? What do they mean?
AB  - Cardiac troponin concentrations are important sensitive and specific markers for
      myocardial injury in clinical medicine. Troponin (TnT) elevations have been noted
      in some series in the setting of acute neurologic disease. We have previously
      reported that solitary seizures do not evoke elevations in TnT. The importance of
      this negative finding is exemplified by a patient who arrived at our clinic
      following a new onset seizure and in whom the cardiac TnT level was observed to
      rise. Triggered by this observation and by the knowledge that seizures alone
      would not do this, a subsequent targeted cardiologic workup documented what was
      believed to be an extension of a previously unrecognized myocardial infarction,
      with a seizure as its clinical presentation. Elevations of troponin should not be
      considered to be due to isolated seizures. This case illustrates the importance
      of having data concerning the response of troponin in various emergency and
      clinical situations.

PMID- 16881546
TI  - Johannes Muller.

PMID- 16881547
TI  - Sudden cardiac death associated with an extremely rare coronary anomaly of the
      left and right coronary arteries arising exclusively from the posterior
      (noncoronary) sinus of Valsalva.

PMID- 16881548
TI  - [Plaut-Vincent's acute necrotizing ulcerative fusospirillum tonsillitis
      associated to infectious mononucleosis].
AB  - We report the case of a 14 years old girl patient with recurrent tonsillitis who
      had been diagnosed and admitted previously with Plaut-Vincent's angina. Six weeks
      after leaving the hospital she was assited in Emergencies by an infectious
      mononucleosis associated to unilateral tonsillar necrotizing ulceration from
      which a sample was taken to microbiological exam finding the fusospirochaetal
      complex Borrelia vincenti and Fusobacterium necrophorum. A literature review at
      the respect of such association and its treatment is performed.

PMID- 16881549
TI  - [Bogorad syndrome or crocodile tears after Ramsay-Hunt].
AB  - Crocodile tears or Bogorad Syndrome describes a complication or sequel after
      facial palsy with incomplete recovery characterized by an excessive
      hyperlacrimation during the food ingestion. We report the case of a 50 years old
      female with that pathology associated to facial syncinesias secondary to suffer a
      right Ramsay-Hunt syndrome. Its pathogenesis and different treatment modalities
      are analysed.

PMID- 16881550
TI  - [Cervical abscess by Streptococcus anginosus-milleri after foreign body ingestion
      and suspicion of esophageal perforation].
AB  - We report a case of cervical abscess after the ingestion of foreign body (chicken
      bone) secondary to probable esophageal perforation that it was sent to us with
      suspicion of mediastinal complication. The girl, 17 years-old, nothing else to
      arrive our hospitalary center required entrance in ICU due to her severe clinical
      process: High fever, intense neck-thoracic pain, laterocervical diffuse and
      progressive left inflammation and bad general state. The CT showed the presence
      of a well defined abscess and abundant aerial component that dissected the
      cervical muscles that made necessary to perform drainage verifying
      intraoperatively no mediastinal involvement. The culture of the purulent
      collection revealed Streptococcus anginosus/milleri resistant to clindamicine but
      sensible to penicilina and derivatives. We exposed a serie of considerations at
      respect of such microorganism and its clinical signification.

PMID- 16881551
TI  - [Unspecific cervical cellulitis of sudden appearance. Report of an atypical
      case].
AB  - We report an atypical case of sudden and unspecific cervical cellulitis in a 74
      yaers old woman with psoriasis as the only remarkable antecedent. After the
      initial exploration and successive ones we did not find any etiological causes
      for her symptoms. CT showed an increase of soft parts on the left side of the
      neck with displacemnet of the upper airway without purulent collection or
      abscess. The patient was admitted in IUC and was treated endovenously with
      cloxaciline and imipenem with good response and satisfactory evolution.

PMID- 16881552
TI  - [Laryngeal chondrosarcoma of low grade of malignancy. Report of a case located on
      thyroid cartilage].
AB  - Cartilaginous tumors of the larynx are rare. Only a 2-5% of all chondrosarcomas
      arise on head and neck area while the laryngeal forms represent less than 1% of
      the malignant neoplasms in that location. Laryngeal chondrosarcoma is three times
      more frequent in men than in women with average age of presentation about the 6th
      - 7th decades. Most of them are originated on cricoid (70-75%) followed by the
      thyroid cartilage (10-20%) as in the case that we are reporting. Its growth often
      is very slow with delayed clinic being hoarseness, dyspnea and dysphagia the most
      common symptoms. Laryngeal chondrosarcomas use to be tumors with low-grade of
      malignancy and their elective treatment is surgery preserving the laryngeal
      function. Local and late recurrences are frequent and the definitive diagnosis is
      the anatomopathological exam.

PMID- 16881553
TI  - [Pronostic value of the immunohistochemical expression of cyclin D1 (DCS6) in
      epidermoid larynx carcinoma].
AB  - In this paper we carried out an immunohistochemical study of cyclin D1 (DCS6 )
      expression in a series of 195 patients with laryngeal carcinoma that were
      diagnosticated, treated and followed at the Department of Otolaryngology at
      "Virgen de la Salud" Hospital (Toledo, Spain) for a time of 5 years. In the cases
      with lymph node metastasis we also studied cyclin D1 expression at this level.
      Furthermore we have analysed the value of cyclin D1 expression as a prognostic
      factor (tumor recurrence, deads due to cancer and survival) and we evaluate the
      relationship between cyclin D1 expression and other clinic and pathologic
      parameters.

PMID- 16881554
TI  - [Amyotrophic lateral sclerosis that begins with voice and deglution alterations].
AB  - Amyotrophic lateral sclerosis is a progressive degenerative neuromuscular disease
      of insidious onset. It involves upper and lower motor neurons and causes both
      spastic and atrophic muscular symptoms. More than one fourth of patients have
      complaints relating to the head and neck (bulbar palsy); thus, the
      otolaryngologist may be the first physician to see them. In bulbar forms of
      Amyotrophic Lateral Sclerosis, voice and/or swallowing difficulties are often the
      initial signs of disturbance. Predominant symptoms are slurred speech,
      hoarseness, dysphagia, and dyspnea. Muscular weakness, atrophy, and fasciculation
      are noted on examination. We show a case and revise bibliography.

PMID- 16881555
TI  - [Eosinophils in nasal polyposis pathogenia. Bibliographic revision].
AB  - The aim of this work is to do a review on relations between the eosinophils and
      nasosinusal polyps. The etiopathogenical action of eosinophils are reviewed, from
      bone narrow to nasal mucosa infiltration. The mechanism of tissue eosinophilic
      mediated inflammation, his regulation and the significance of the balance between
      positive (IL-5) and negative (TGFbeta and IL10) mediators are discussed. We
      conclude that the degree of eosinophilic infiltration and degranulation's
      patterns are important aspects conditioning the severity and prognosis of chronic
      rhinosinusitis and nasosinusal polyps.

PMID- 16881556
TI  - [Topic usage of bismuth subgallate as a hemostatic in tonsillectomy].
AB  - The most feared complication for the ENT specialists in the adenotonsillectomy is
      the immediate or mediate haemorrhage after surgery. We revise the literature and
      contrast experiencies with other colleage. We have found an astringent substance
      (bismuth subgallate), which helps us give an exact intraoperative diagnosis of
      the bleeding spot by the colour contrast it shows, and serves us also as a
      hemostatic, since it activates the XII factor in coagulation. We revise this
      product regarding its origen, prentation, applications and toxic effects.

PMID- 16881557
TI  - [Respiratory stridency by larynx paralysis. Anusual beginning of miastenia].
AB  - A case of severe miastenia beginning with dyspnea, secondary to a bilateral
      larynx paralysis in aduction is presented. During the evolution of the severe
      miastenia the affectation of the larynx musculature does not result infrequent,
      but however, after having realized a bibliographic revision, the infrequency
      resulting in this disease of the beginning through a bilateral larynx paralysis
      in aduction was verified. A wide exposition of the clinic case, methods of
      exploration to obtain the diagnosis of severe miastenia, and the different
      treatment options actually in use to control these disease, are realized.

PMID- 16881558
TI  - [Diagnostic and treatment of necrotizing cervical fascitis. Clinical course after
      a Ludwig angina].
AB  - The Ludwig angina is an infection of the base of the mouth and submandibular
      region, frecuently after a dental extraction or a piece in bad state. When it
      surpassees the milohioid muscle it extends dissecting the superficial aponeurotic
      planes, and can evolve to a necrotisant fascitis. We present the case of a 67
      years old man with a painful tumefaction of the mouth base and submandibular
      region. The CT reflected an heterogenous submaxilar lesion that extended by the
      deep cervical fascia introducing itself in the thorax. Under antibiotic treatment
      the pus was drained by cervicotomy, with daily cures during 3 weeks.

PMID- 16881559
TI  - Emergency preparedness and disability.

PMID- 16881560
TI  - Prevalence of sedative drug use in geriatric in-patients: a multi-centre study.
AB  - OBJECTIVE: This cross-sectional study registered the prevalence of sedative drug
      use and withdrawal strategies in geriatric in-patients from 30 centres in nine
      European countries. METHODS: We conducted a survey among young geriatricians
      using a standardised questionnaire on sedative drug use for more than three
      weeks. The study population consisted of 1972 in-patients aged 75 years or older.
      Acute care (620), intermediate care/rehabilitation (359), long-term care (261),
      terminal care (47) and nursing home (685) settings were represented. The pre
      specified outcomes included the prevalence of sedative drug use; the
      identification of main prescribers and main reasons for prescribing and, the
      assessment of withdrawal policy, including psychological counselling and
      involvement of general practitioners. RESULTS: Prevalence of sedative use was
      highest in long-term care (72%), followed by nursing homes (70%) and terminal
      care (59%). Geriatricians started prescribing sedatives after admission on 52% of
      all occasions. The main reasons for prescribing were continuation of medication
      taken at home (37%), sleep problems emerging after admission (26%) and post
      admission worsening of existing sleep problems (20%). Most prescribers (70%)
      applied an active withdrawal policy. Short-term withdrawal programmes were mostly
      applied (57%). Most patients (60%) were psychologically counselled during
      withdrawal from sedatives. General practitioners were often (60%) involved in
      withdrawal policy. CONCLUSION: The prevalence of prescription of sedative drugs
      in geriatric in-patients is high. Appropriate setting specific guidelines are
      needed to control use of sedatives in geriatric in-patients and to ensure
      withdrawal from these drugs whenever possible.

PMID- 16881561
TI  - Metabolic (glycaemic, lipidic) and blood pressure control in 101 type 2 diabetic
      patients on first admission to diabetes centres.
AB  - The aim of our study was to analyse the quality of metabolic and blood pressure
      control in a cohort of 101 patients with type 2 diabetes (54 males; 47 females),
      previously followed in primary care settings and admitted for the first time to
      the diabetes centres of Saint-Luc (n=66) or Mont-Godinne (n=35) University
      Hospitals. Age and (known) duration of diabetes were 64 +/-12 and 6 +/- 7 years
      (mean +/- SD), respectively. Body mass index was 31 +/- 7 kg/m2. Systolic and
      diastolic blood pressures were 140 +/-12 and 81 +/-11 mmHg. Homeostasis model
      assessment (HOMA) showed insulin sensitivity at 63 +/-32% and P-cell function at
      49 +/- 44% (n=34). Forty-seven percent of patients received either diet alone or
      combined with an oral antidiabetic monotherapy. Seven-teen percent of all
      patients were on insulin monotherapy or associated with oral drugs. HbAlc was 9.0
      +/- 2.3%, with 22% of patients within HbAlc targets of < or = 7%. Only a subset
      of patients reached international targets of care in terms of blood pressure and
      lipidic profile, despite antihypertensive and lipid-lowering agents in 62% and
      36% of patients, respectively. Forty-five percent of individuals had at least one
      diabetes-related long-term complication. In view of this unsatisfactory control,
      our results suggest that "anti-diabetic" treatment should be intensified earlier
      in primary care settings.

PMID- 16881562
TI  - Hypophosphatemia and refeeding: a corrective or a preventive attitude?
AB  - Hypophosphatemia is a rare but potentially lethal complication of the refeeding
      of cachectic patients. Up until now a careful monitoring of the serum phosphor
      level was recommended and the deficit was corrected as needed. Illustrated by two
      case reports we propose the use of a preventive schedule in patients with a
      normal renal function. We show that preventively treated patients do not develop
      hypophosphatemia and thereby avoid serious complications such as sudden death. In
      the presence of normal kidney function we propose to administer phosphor at 2 x
      10 mmol/day orally or between 10 and 30 mmol IV depending on the initial phosphor
      levels. Further treatment is then adapted to measured levels. In the presence of
      kidney malfunction we propose to keep the corrective schedule.

PMID- 16881563
TI  - Diagnostic markers of sepsis in the emergency department.
AB  - Sepsis is defined as the systemic inflammatory response to infection. However,
      changes in body temperature, heart and respiratory rate and white cell count (the
      "SIRS" criteria) are not specific enough to identify infected patients in the
      emergency department. Among many biological parameters, measurement of lactate,
      central venous oxygen saturation (ScvO2), C-reactive protein (CRP) and
      procalcitonin (PCT) are of particular interest. Early (within 6h) and goal
      directed (ScvO2 > 70%) resuscitation increases survival in severe sepsis and
      septic shock, particularly in patients with high lactate clearances. CRP and PCT
      are both useful markers of sepsis but PCT increases earlier, better
      differentiates infective from non-infective causes of inflammation, more closely
      correlates with sepsis severity in terms of shock and organ dysfunction and
      better predicts outcome when followed in time. However, PCT measurement is more
      costly, time-consuming, and not widespread available. New markers for rapid
      diagnosis of sepsis (e.g. TREM-1) are under investigation.

PMID- 16881564
TI  - [Monitoring of adipocyte responsiveness by in situ microdialysis in lipodystrophy
      tissue: adjustment of a glycerol quantification method in small samples].
AB  - In situ microdialysis allows monitoring of metabolic cellular processes at the
      tissue level in vivo. In the assessment of physiopathologic alterations seen in
      lipodystrophy, monitoring of glycerol release is pivotal. Indeed, it allows to
      quantify the pharmacological responsiveness of subcutaneous adipose tissue in
      humans. Until now, the small volume of microdialysate collected (5-15
      microL/sample) restricted the assessment of glycerol level to the use of the
      radio-enzymatic method or the reference spectrophotometric microanalysis
      technique. The aim of this study was to adapt the method of glycerol measurement
      by iminequinone spectrophotometry colorimetric assay (520 nm) using the following
      reagent: 0.5 IU Glycerokinase, 1.23 IU glycerophosphate oxidase, 0.98 IU
      peroxidase, 4.6 mM Mg, 5.4 mM 4-chlorophenol, 0.25 mM 4-aminoantipyrine and 1.4
      mM ATP. The assay was setup to run on Olympus AU 2700 automate (15 pL sample
      volume). The sensitivity of the method was improved by adding a 0.2 mmol
      triglyceride (TG) solution and 1.5 IU lipase to samples, reducing the limit of
      free glycerol quantification to 0.020 mmol/L. The analytical repeatability was
      2.0% and the reproducibility was 7.9%. The present method thus demonstrated the
      feasibility of pharmacodynamic exploration of local cutaneous responsiveness in
      vivo in clinical trials.

PMID- 16881565
TI  - Pulmonary amyloidosis in familial Mediterranean fever.
AB  - Familial Mediterranean Fever (FMF) is a hereditary periodic fever syndrome
      expressed by acute episodes of fever and painful manifestations. The gravest
      consequence of FMF is kidney involvement by secondary amyloidosis of AA type,
      which gradually leads to nephrotic syndrome and uremia. Nephropathic amyloidosis
      of the AA type, which complicates FMF in most untreated patients, may progress to
      effect other organs, including the lungs. This kind of organ involvement rarely
      produces noticeable symptoms and is associated with symptomatic involvement of
      other organs while remaining subclinical in itself. In this report, one case who
      had nephropathic and pulmonary amyloidosis of the secondary amyloidosis of AA
      type, wich complicates the FMF was presented and the pulmonary manifestations of
      FMF were reviewed.

PMID- 16881566
TI  - Coriander anaphylaxis in a spice grinder with undetected occupational allergy.
AB  - BACKGROUND: Anaphylaxis after ingestion of spices as a result from occupational
      sensitization remains anecdotal. We describe a patient, working in a spice
      factory, with anaphylaxis from coriander in a meal. He also demonstrated
      urticaria, angio-edema, rhinoconjunctivitis and bronchospasm during handling
      coriander and fenugreek. OBJECTIVE: To determine the mechanism of the
      anaphylactic reaction and to evaluate cross-reactivity between both botanically
      unrelated spices. METHODS: Investigations comprised quantification of total and
      specific IgE by Immuno-CAP FEIA, skin testing, basophil activation experiments by
      flow-assisted determination of CD63 expression in the patient and 3 healthy
      controls. Immuno-CAP inhibition experiments were applied to investigate cross
      reactivity. RESULTS: Specific IgE, skin tests and basophil activation tests were
      clearly positive in the patient, whereas they remained negative in controls. No
      cross-reactivity between fenugreek and coriander was demonstrable by inhibition
      experiments. CONCLUSIONS: The clinical manifestations in temporal relationship to
      ingestion of coriander and handling of coriander and/or fenugreek, the positive
      specific IgE results, skin tests and basophil activation assays support the
      diagnosis of allergy to both spices. History suggests sensitization by
      occupational exposure.

PMID- 16881567
TI  - A new DRG system for IPPS.

PMID- 16881568
TI  - The code ahead: Key issues shaping clinical terminology and classification.

PMID- 16881569
TI  - Computer-assisted coding: what's here, what's ahead.

PMID- 16881570
TI  - Implementing SNOMED CT in England.

PMID- 16881571
TI  - The perfect time for documentation improvement.

PMID- 16881572
TI  - A look at LOINC.

PMID- 16881573
TI  - Architecture of the FHIE.

PMID- 16881574
TI  - A resource for privacy and security programs.

PMID- 16881575
TI  - The evolution of DRGs.

PMID- 16881577
TI  - Speaking the IT lingo.

PMID- 16881576
TI  - Privacy and security challenges in HIEs.

PMID- 16881578
TI  - Determining surgical complications.

PMID- 16881579
TI  - The pathophysiology of hypovolemia and dehydration.

PMID- 16881580
TI  - Big results at a small facility.

PMID- 16881581
TI  - In good council. Interview by Christian Duffin.

PMID- 16881582
TI  - Will RCN headquarters be sold to wipe out the pensions deficit?

PMID- 16881583
TI  - Women are the answer. Interview by Colin Parish.
AB  - Women are suffering in far greater numbers than men in the HIV/AIDS disaster in
      Africa. Stephen Lewis, the United Nations special envoy for HIV/AIDS in Africa,
      says a global approach is needed to stem the tide of misery. Nurses can play
      their part too.

PMID- 16881584
TI  - Caring for the children.
AB  - KwaZulu Natal has the highest rates of HIV/AIDS in South Africa. Teams of British
      nurses and doctors visit the province regularly to help staff there learn about
      antiretroviral therapy.

PMID- 16881586
TI  - When did I get to be an old man?

PMID- 16881585
TI  - All for one.
AB  - There is a growing body of evidence that transferring a single embryo--rather
      than the current practice of two--during in vitro fertilisation is effective and
      could result in costs savings.

PMID- 16881587
TI  - Against the grain.

PMID- 16881588
TI  - Meeting the nutritional needs of patients with dementia in hospital.
AB  - This is the third article in a series of five focusing on the needs of patients
      with dementia. It emphasises the importance of good nutritional intake for
      patients with dementia in hospital care. On busy wards, nutrition is often
      overlooked in favour of other aspects of care. Nurses' increased knowledge about
      dementia, assessment of nutritional needs, and personal capabilities can improve
      patients' experiences and outcomes. Excess dependency and emotional aspects of
      food refusal are also discussed.

PMID- 16881590
TI  - Communication in palliative care.

PMID- 16881589
TI  - The physiological effects of ageing on the activities of living.
AB  - This article describes different theories of ageing. It examines the impact that
      physiological effects have on aspects of living for older people: eating and
      drinking, eliminating, mobilising, communicating and breathing.

PMID- 16881591
TI  - Assessment and management of patients with surgical cavity wounds.
AB  - This article explores the management of surgical cavity wounds. The effectiveness
      of healing depends on wound assessment and constant re-evaluation of the
      management strategy adopted. Management strategies should be holistic and take
      into account the wound bed and local and systemic barriers to healing, as well as
      patients' thoughts and concerns about their wound. Nurses have a pivotal role in
      wound management and dressing selection, and should aim to keep up to date in
      this dynamic specialty.

PMID- 16881592
TI  - Two-layer compression hosiery for patients with venous leg ulceration.
AB  - Patients may experience a recurrence of leg ulceration if they do not wear
      prescribed compression hosiery when ulcers have healed. This article examines the
      use of compression hosiery kits, which can be used for the treatment of active
      ulceration as well as prevention of recurrence. For some patients, the stockings
      may be easier to apply than traditional compression hosiery, thereby enabling
      them to benefit from continued wear.

PMID- 16881593
TI  - Face up to responsibility.

PMID- 16881594
TI  - Beyond the emergency.

PMID- 16881595
TI  - International Journal of Occupational Medicine and Environmental Health in world
      documentation services: the SCOPUS based analysis of citation.
AB  - A high classification of scientific journals in the ranking of international
      transfer of knowledge is reflected by other researchers' citations. The
      International Journal of Occupational Medicine and Environmental Health (IJOMEH)
      is an international professional quarterly focused on such areas as occupational
      medicine, toxicology and environmental health edited in Poland. IJOMEH, published
      in English, is indexed in numerous world information services (MEDLINE, EMBASE,
      EBSCO, SCOPUS). This paper presents the contribution of IJOMEH publications to
      the world circulation of scientific information based on the citation analysis.
      The analysis, grounded on the SCOPUS database, assessed the frequency of
      citations in the years 1996-2005. Journals in which they have been cited were
      retrieved and their list is also included.

PMID- 16881596
TI  - De minimus non curat lex--virtual thresholds for cancer initiation by tobacco
      specific nitrosamines--prospects for harm reduction by smokeless tobacco.
AB  - Whereas the impact of tobacco specific nitrosamines in smokers is obscured by the
      presence of numerous other carcinogens and promoters, for smokeless tobacco
      virtually all the carcinogenic potential is associated with 4
      (nitrosomethylamino)-1-(3-pyridyl)-1-butanone (NNK) and N'-nitrosonornicotine
      (NNN). In some countries exposure to smokeless tobacco with extremely high
      nitrosamine concentrations have been found to induce cancers in the head-neck
      region, whereas three recent large epidemiological studies failed to detect any
      such risk with respect to Swedish low-nitrosamine snuff. This review deals with
      quantitative aspects of DNA adduct formation from NNN and NNK in relation to the
      background levels ubiquitously found in healthy humans without known exposures to
      either tobacco or alkylating agents. The lack of significant increases of pro
      mutagenic O6-methylations and DNA pyridyloxobutylations seen in smokers, as well
      as the negative outcome of the Swedish epidemiological studies, can be expected
      on basis of extrapolation of the dose response relationships found in rodents to
      actual exposures to NNK and NNN in Swedish snuff or from smoking. Sweden has the
      lowest prevalence of male smokers and smoking related diseases in the Western
      World, which has been ascribed to the fact that more than 20% of the grown up
      male population uses snuff. Smokeless tobacco represents an inexpensive and
      effective alternative to nicotine delivering products like nicotine patch, spray
      or gum. Considering that all other tobacco products are freely marketed, the ban
      on low-nitrosamine snuff in all countries in EU except Sweden is difficult to
      defend on either medical or ethical grounds.

PMID- 16881597
TI  - Hazardous effects of arsine: a short review.
AB  - This review details the known health effects of arsine as well as the existing
      theories on the mechanism by which arsine exerts its toxic effect and conditions
      of occupational exposure to this gas. Exposure to arsine in occupational settings
      occurs mostly in the chemical and metallurgical industries when nascent hydrogen
      reacts with metallic arsenic or arsenic compounds. The available data indicate
      that in these branches of industry arsine is often a cause of unexpected serious
      poisoning. The gas affects primarily blood and kidneys. Acute arsine poisoning is
      known to result in massive damage to red blood cells through the oxidative
      mechanism, probably by the formation of hydrogen peroxide and adducts with
      oxyhemoglobin. According to another hypothesis, arsine acts on sodium-potassium
      pomp mechanism, producing subsequent red blood cell swelling and hemolysis. Rapid
      hemolysis may lead to oliguric renal failure and death. Symptoms of chronic
      poisoning are similar to those observed in acute poisoning. The main difference
      is a longer latency period. Late effects of chronic exposure to low levels of
      arsine have not yet been precisely identified.

PMID- 16881598
TI  - The role of XRCC1 polymorphisms in base excision repair of etheno-DNA adducts in
      French vinyl chloride workers.
AB  - OBJECTIVES: The purpose of this study was to examine whether polymorphisms in the
      XRCC1 DNA-repair protein can affect the base excision repair capacity to remove
      etheno-DNA adducts induced by vinyl chloride exposure that account for the
      occurrence of mutant biomarkers of effect seen in exposed workers. MATERIALS AND
      METHODS: Using polymerase chain reaction-restriction fragment length polymorphism
      and fluorescence polarization techniques, we examined the effect of three x-ray
      cross complementing-1 protein polymorphisms, at codons 194, 280 and 399, on the
      occurrence of mutant biomarkers in ras-p21 and p53 induced by vinyl chloride
      exposure in a cohort of 211 French vinyl chloride workers to correlate
      differences in genotype with differences in the presence of these biomarkers.
      Also, cell cultures of lymphoblast lines from a pair of individuals, one
      homozygous wild-type and one homozygous variant for the codon 399 polymorphism,
      were exposed to the reactive intermediate of vinyl chloride, and, using an enzyme
      linked immunosorbent assay, levels of etheno-DNA adducts generated and repaired
      were measured and compared. RESULTS: After adjusting for age, smoking, alcohol
      drinking and cumulative vinyl chloride exposure, compared to workers who were
      homozygous wild-type for all alleles, the odds ratio for the presence of either
      biomarker increased to 2.0 (95% CI: 1.0-3.9) for workers with any one variant
      allele and to 2.4 (95% CI: 1.1-5.2) for workers with more than one variant
      allele. Data from the cell culture experiments indicating that repair of etheno
      DNA adducts is considerably better in wild-type cells compared to polymorphic
      cells were supportive of the epidemiologic results. CONCLUSIONS: This study
      provides further evidence that polymorphisms in XRCC1 can be an important
      biomarker of susceptibility in populations exposed to agents that produce damage
      removed by base excision repair.

PMID- 16881599
TI  - Neurovegetative disturbances in workers exposed to 50 Hz electromagnetic fields.
AB  - OBJECTIVES: Since the circulatory and nervous systems are composed of
      electrically excitable tissues, it is plausible that they can be stimulated by
      electromagnetic fields (EMF). No clinical studies have as yet been carried out to
      explain whether and how occupational exposure to 50 Hz EMF can influence the
      neurovegetative regulation of the cardiovascular function. The present project
      was undertaken to assess the autonomic function in workers occupationally exposed
      to 50 Hz EMF, by analyzing the heart rate variability. MATERIALS AND METHODS: The
      study group comprised 63 workers of switchyard substations, aged 22-67 years
      (39.2 +/- 10.0 years), and the control group 42 workers of radio link stations,
      aged 20-68 years (40.7 +/- 9.2 years), employed at workposts free from EMF
      exposure. The age range and employment duration in both groups did not differ
      significantly. To assess the neurovegetative regulation of the cardiac function,
      heart rate variability (HRV) analysis was made based on 512 normal heart beats
      recorded at rest. The analysis, performed using fast Fourier transformation,
      concerned the time- and frequency-domain HRV parameters. Power spectrum in the
      very low (VLF), low (LF) and high (HF) frequency bands was determined. RESULTS:
      The relative risk of decreased HRV (STD R-R < 27 ms), calculated with use of a
      logistic regression model, was significantly higher in the exposed group than in
      controls (OR = 2.8). The VLF power spectrum was significantly higher in the
      exposed group and correlated with the exposure level. The percentage of subjects
      with dominant sympathetic function (LF/HF > 1) was significantly higher in the
      study group than in controls (65% vs. 47%). CONCLUSIONS: It was concluded that
      occupational exposure to 50 Hz EMF could influence the neurovegetative regulation
      of the cardiovascular system.

PMID- 16881600
TI  - Physical activity and self-perceived health status.
AB  - OBJECTIVES: Recently more attention has been focused on the impact of physical
      activity on modification of self-perceived heath status in adults. The objective
      of the study was to evaluate the level of occupational and non-occupational
      physical activities and their correlation with self-perceived heath status among
      economically productive individuals. MATERIALS AND METHODS: Physical activity of
      the subjects studied was evaluated by the Seven Day Physical Activity Recall
      (SDPAR) questionnaire among randomly chosen residents of the city of Lodz (n =
      598, including 299 women and 299 men). The examination of the subjective health
      assessment was conducted based on the analogue visual scale. RESULTS: The
      multifactorial logistic regression analysis indicated that weekly energy
      expenditure on occupational physical activity (kcal/week) did not play a
      significant role in self-perception of health status among men or women. Neither
      did the outcome of the study provide evidence for the significant effect of
      housework load on self-perceived health status among the study participants.
      However, a sufficient level of leisure-time physical activity in a beneficial way
      affects health-related self-perception of the examined subjects. In the group of
      men expending 1000 kcal/week or more on leisure-time physical activity, the risk
      for poor health-related self-report was significantly lower than among men
      declaring no energy expenditure on this activity (adjusted odds ratio (OR = 0.29,
      95% CI: 0.13-0.66). Among females not taking up any recreational physical
      activity, the risk of low self-perceived health status was also higher than in
      females reaching a satisfactory level of recreational physical activity (adjusted
      OR = 0.38, 95% CI: 0.17-0.87). CONCLUSIONS: Preventive programs aimed at
      improving subjective health assessment through the increased leisure-time
      physical activity should be addressed to all economically productive individuals
      and particularly to people of older age groups and above all to females.

PMID- 16881601
TI  - The prenatal use of antibiotics and the development of allergic disease in one
      year old infants. A preliminary study.
AB  - OBJECTIVES: Recent research has suggested that the protective effect of natural
      infections may be due to their influence on the development of the immune system
      in early life. The purpose of the study was to determine whether maternal use of
      antibiotics during pregnancy is a risk factor for wheezing and allergy in early
      infancy. MATERIALS AND METHODS: Nonsmoking women, aged 18-35 years, were enrolled
      in 2000/2001 from prenatal clinics during the second or third trimester of
      pregnancy. After delivery, newborns were followed-up every three months over one
      year and trained interviewers conducted a standardized interview with mothers on
      infants' health at each visit held every three-month. In total, 102 infants were
      followed over a one-year period and questionnaires on the use of various
      medications during pregnancy and potential risk factors for allergy and asthma
      were completed. Relative risk for persistent wheezing (9+ days over the follow
      up) adjusted for potential confounders was significantly associated with the
      duration of antibiotic therapy, however, it was significant only if the
      antibiotic treatment took place in the second and the third trimester. RESULTS:
      The adjusted relative risk was increasing by 14% with each day of using
      antibiotics compared with the reference group (RR = 1.14; 95% CI: 1.01-1.27).
      When usage of antibiotics was regarded as a dichotomous variable in the logistic
      model (cut-off point at 5 days), the estimated adjusted risk for persistent
      wheezing was 4.42 (95% CI: 1.05-18.8). The risk for hay fever due to exposure to
      antibiotics was 2.65 (95% CI: 1.03-6.81) and a corresponding estimate for eczema
      was 2.30 (95% CI: 0.91-5.80). CONCLUSIONS: The study suggests that maternal use
      of antibiotics during pregnancy may prove to be a risk factor for persistent
      wheezing and development of allergy in early infancy.

PMID- 16881602
TI  - Occupational allergic contact dermatitis disseminated from multifunctional
      acrylates in ultraviolet-cured lacquers.
AB  - A case of disseminated allergic contact dermatitis in a screen process printer is
      presented. The skin lesions were caused by multifunctional acrylates
      (methylpropane triacrylate and pentaerythritol triacrylate--highly positive patch
      tests (+ + +) after 48 and 96 h) present in ultraviolet cured transparent lacquer
      used in coat printed posters to make them weather-resistant. Patch tests with
      lacquer were also highly positive (+ + +) after 48 and 96 h. According to the
      safety sheet of the product, lacquer contained 85-90% of multifunctional
      acrylates. The patient showed disseminated dermatitis, however, no hypertrophied
      lesions on the hand skin, a characteristic symptom in persons exposed to
      acrylates, were observed.

PMID- 16881603
TI  - Primula allergic dermatitis simulating occupational contact dermatitis induced by
      metals, oils and greases.
AB  - A case of the hands and face dermatitis in a patient employed in a store with
      motor-car spare parts is presented. Both the patient and her doctor were
      convinced that skin lesions were caused by the contact with metals, oils and
      greases. After detecting allergy to primine (after 48 and 96 h, + +), the patient
      recalled that two months earlier she had started to grow primrose (Primula
      obconica) at home. Patch tests with the primrose leaf and flower were also
      positive (+ +). The presented case provides evidence that routine primine testing
      is essential in all patients with suspected contact allergy dermatitis. In Poland
      like in the majority of countries, primina is not included in the standard kit.

PMID- 16881604
TI  - Polyhexamethylenebiguanide hydrochloride exposure and erythema multiforme in a
      physician.
AB  - A 52-year-old woman physician developed recurrent erythema multiforme.
      Occupational and environmental exposure assessment suggested a disinfectant
      containing polyhexamethylenebiguanide hydrochloride (PHMB), Phagosept.
      Elimination of the product was followed by disappearance of symptomatology.
      Literature search revealed cases of sensitization and anaphylaxis due to contact
      with PHMB, but to our knowledge, this is the first report on PHMB-induced
      erythema multiforme.

PMID- 16881605
TI  - Global surveillance of DDT and DDE levels in human tissues.

PMID- 16881606
TI  - Photoinduced charge transfer between CdSe nanocrystal quantum dots and Ru
      polypyridine complexes.
AB  - In this communication, we demonstrate a new approach to sensitization of Ru
      polypyridine complexes by using semiconductor nanocrystal quantum dots (NQDs).
      When mixed in solution, the complexes functionalized by carboxylic groups adsorb
      onto the surface of the NQDs. Excitation of NQDs by 400 nm light leads to fast, 5
      ps hole transfer from the photoexcited NQDs to the surface-adsorbed complexes.
      This result indicates that Ru complexes can be sensitized by CdSe NQDs, which
      opens interesting opportunities for designing new types of photocatalytic
      materials for solar energy conversion applications. These materials will take
      advantage of broad size-controlled absorption spectra and large extinction
      coefficients of NQDs as well as the unique property of NQDs to respond to
      absorption of a single photon by producing multiple electron-hole pairs.

PMID- 16881607
TI  - Hybrid molecular probe for nucleic acid analysis in biological samples.
AB  - The ability to detect changes in gene expression, especially in real-time and
      with sensitivity sufficient enough to monitor small variations in a single-cell,
      will have considerable value in biomedical research and applications. Out of the
      many available molecular probes for intracellular monitoring of nucleic acids,
      molecular beacon (MB) is the most frequently used probe with the advantages of
      high sensitivity and selectivity. However, any processes in which the MB stem
      loop structure is broken will result in a restoration of the fluorescence in MB.
      This brings in a few possibilities for false positive signal such as nuclease
      degradation, protein binding, thermodynamic fluctuation, solution composition
      variations (such as pH, salt concentration) and sticky-end pairing. These
      unwanted processes do exist inside living cells, making nucleic acid monitoring
      inside living cells difficult. We have designed and synthesized a hybrid
      molecular probe (HMP) for intracellular nucleic acid monitoring to overcome these
      problems. HMP has two DNA probes, one labeled with a donor and the other an
      acceptor. The two DNA probes are linked by a poly(ethylene glycol) (PEG) linker,
      with each DNA being complementary to adjacent areas of a target sequence. Target
      binding event brings the donor and acceptor in proximity, resulting in quenching
      of the donor fluorescence and enhancement of the acceptor emission. The newly
      designed HMP has high sensitivity, selectivity, and fast hybridization kinetics.
      The probe is easy to design and synthesize. HMP does not generate any false
      positive signal upon digestion by nuclease, binding by proteins, forming
      complexes by sticky-end pairing, or by other molecular interaction processes. HMP
      is capable of selectively detecting nucleic acid targets from cellular samples.

PMID- 16881608
TI  - Tuning the sensitivity of a foldamer-based mercury sensor by its folding energy.
AB  - A fluorescent sensor for Hg2+ was obtained by incorporation of two methionine
      units into a cholate hexamer and by attaching a Dansyl group at the chain end.
      Folding could be made highly favorable or unfavorable in different solvents.
      Because folding was required to bring the sulfur groups together to chelate the
      mercury ion, binding affinity of the foldamer and, thus, its sensitivity as a
      sensor, could be tuned over broad ranges (at least 5 orders of magnitude) by
      solvent changes.

PMID- 16881609
TI  - Covalent attachment of acetylene and methylacetylene functionality to Si(111)
      surfaces: scaffolds for organic surface functionalization while retaining Si-C
      passivation of Si(111) surface sites.
AB  - Si(111) surfaces have been functionalized with Si-CC-R species, where R = H or 
      CH3, using a two-step reaction sequence involving chlorination of H-Si(111)
      followed by treatment with Na-CC-H or CH3-CC-Na reagents. The resulting surfaces
      showed no detectable oxidation as evidenced by X-ray photoelectron spectroscopic
      (XPS) data in the Si 2p region, electrochemical measurements of Si-H oxidation,
      or infrared spectroscopy. The Si-CC-R-terminated surfaces exhibited a
      characteristic CC stretch in the infrared at 2179 cm-1, which was strongly
      polarized perpendicular to the Si(111) surface plane. XPS measurements in the C
      1s region showed a low binding energy peak indicative of Si-C bonding, with a
      coverage that was, within experimental error, identical to that of the CH3
      terminated Si(111) surface, which has been shown to fully terminate the Si atop
      sites on an unreconstructed Si(111) surface. The Si-CC-H-terminated surfaces were
      further functionalized by exposure to n-C4H9Li followed by exposure to para Br
      C6H5-CF3, allowing for introduction of para -C6H5CF3 groups while maintaining the
      desirable chemical and electrical properties that accompany complete Si-C
      termination of the atop sites on the Si(111) surface.

PMID- 16881610
TI  - Constant-time through-bond 13C correlation spectroscopy for assigning protein
      resonances with solid-state NMR spectroscopy.
AB  - Even as available magnetic fields for NMR continue to increase, resolution
      remains one of the most critical limitations in assigning and solving structures
      of larger biomolecules. Here we present a novel constant-time through-bond
      correlation spectroscopy for solids that offers superior resolution for 13C
      chemical shift assignments in proteins. In this experiment, the indirect
      evolution and transfer periods are combined into a single constant time interval,
      offering increased resolution while not sacrificing sensitivity. In GB1, this
      allows us to resolve peaks that are otherwise unresolved and to make assignments
      in the absence of multibond transfers.

PMID- 16881611
TI  - Redox ionic liquid phases: ferrocenated imidazoliums.
AB  - This communication reports the synthesis of new intrinsically electroactive N
      alkyl imidazolium ionic liquids useful for the investigation of charge transport
      phenomena in undiluted semisolid redox media. The redox site chosen is ferrocene,
      but the overall approach should be general for designing imidazolium-based molten
      salts. The ferrocene is attached to imidazolium with several structural
      variations, and preliminary voltammetry of a melt is presented.

PMID- 16881612
TI  - Efficient non-corrosive electron-transfer mediator mixtures for dye-sensitized
      solar cells.
AB  - The electrochemical and photoelectrochemical study of noncorrosive electron
      transfer mediator mixtures for DSC is reported. These mixtures, characterized by
      the presence of kinetically fast organic or metal-organic redox couples in
      conjunction with a Co(II)/(III) relay, exhibited maximum photon-to-current
      conversion efficiencies (IPCE %) exceeding 80% when employed in the presence of a
      suitably designed MLCT sensitizer, rivaling with the performances of the
      classical I-/I3- electrolyte.

PMID- 16881613
TI  - Highly efficient alkylation to ketones and aldimines with Grignard reagents
      catalyzed by zinc(II) chloride.
AB  - A highly efficient alkylation to ketones and aldimines with Grignard reagents in
      the presence of catalytic trialkylzinc(II) ate complexes derived from ZnCl2 (10
      mol %) in situ was developed. This simple Zn(II)-catalyzed alkylation could
      minimize the well-known but serious problems with the use of only Grignard
      reagents, which leads to reduction and aldol side products, and the yield of
      desired alkylation products could be improved.

PMID- 16881614
TI  - Detection and structural characterization of clusters with ultrashort-lived
      electronically excited states: IR absorption detected by femtosecond multiphoton
      ionization.
AB  - The vibrational fingerprint of the electronically excited short-lived complex of
      1-H-pyrrolo[3,2-h]quinoline:methanol was measured using femtosecond multiphoton
      ionization detected infrared (IR/fsMPI) spectroscopy under supersonic jet
      conditions. A cyclic doubly hydrogen-bonded structure of the cluster has been
      proven from the comparison of the measured vibrational spectrum with that
      calculated with density functional theory. The employed nsIR-fsUV double
      resonance scheme is shown to be an effective tool for structural analysis of
      precursors that undergo fast deactivation and/or photoreactions.

PMID- 16881615
TI  - Synthesis of homoallylic amines via the palladium-catalyzed decarboxylative
      coupling of amino acid derivatives.
AB  - Protected homoallylic amines are synthesized by the decarboxylative coupling of
      alpha-amino acid derivatives. The catalytic C-C bond-forming reaction relies on
      the bioinspired decarboxylative metalation of alpha-amino acids to produce alpha
      amino anion equivalents. The alpha-amino anion equivalents are intercepted by pi
      allyl palladium electrophiles to produce substituted homoallylic amines.

PMID- 16881616
TI  - Inter-helix distances in lysophospholipid micelle-bound alpha-synuclein from
      pulsed ESR measurements.
AB  - We demonstrate the use of pulsed ESR spectroscopy to measure intramolecular
      distances in the Parkinson's disease-associated protein alpha-synuclein bound to
      detergent and lysophospholipid micelles. We show that the inter-helical
      separation between the two helices formed upon binding to micelles is dependent
      on micelle composition, with micelles formed from longer acyl chains leading to
      an increased splaying of the two helices. Our data suggest that the topology of
      alpha-synuclein is not strongly constrained by the linker region between the two
      helices and instead depends on the geometry of the surface to which the protein
      is bound.

PMID- 16881617
TI  - Directed self-assembly of gold-tipped CdSe nanorods.
AB  - Gold-tipped CdSe rods (nanodumbbells) were solubilized in an aqueous phase and
      self-assembled in a head-to-tail manner using biotin disulfide and avidin. The
      disulfide end of the biotin molecule attaches to the gold tip of the
      nanodumbbell, and the biotin end of the molecule is able to conjugate to an
      avidin protein. The avidin can strongly conjugate up to four biotin molecules.
      Changing the ratios of biotin to nanodumbbells leads to the formation of dimers,
      trimers, and flowerlike structures. To further improve the distribution of chain
      lengths, a separation method based upon weight was applied using a concentration
      gradient. The gold tips provide effective anchor points for constructing complex
      nanorod structures by self-assembly.

PMID- 16881618
TI  - Distinct dynamic behaviors of water molecules in hydrated pores.
AB  - Water molecules confined inside narrow pores are of great importance in
      understanding the structure, stability, and function of water channels. Here we
      report that besides the H-bonding water that structures the pore, the permanent
      presence of a significant, fast-moving fraction of incompletely H-bonded water
      molecules inside the pore should control the free entry and exit of water. This
      is achieved by means of complementary DSC and solid-state NMR studies. We also
      present compelling evidence from X-ray diffraction data that the cluster formed
      by six water molecules in the most stable cage-like structure is sufficiently
      hydrophobic to be stably adsorbed in a nonpolar environment.

PMID- 16881619
TI  - Pseudo-CSA restraints for NMR refinement of nucleic acid structure.
AB  - Upon alignment of oligonucleotides in a magnetic field, the downfield TROSY
      component of the 13C-{1H} doublet changes its resonance frequency as a result of
      residual 13C-1H dipolar coupling (RDC) and residual 13C chemical shift anisotropy
      (RCSA), and the sum of these two second rank tensors is referred to as the pseudo
      CSA. The experimentally measured difference in the resonance frequency of the 13C
      TROSY component in the aligned and isotropic samples is referred to as residual
      pseudo-CSA (RPCSA), and it can be used directly as a restraint during structure
      calculation. Because measurement of the RPCSA involves detection of the narrow
      TROSY 13C doublet component, it is applicable to systems with larger rotational
      correlation times than RDC measurement. The method is demonstrated for structure
      refinement of the helical region of a 24-nt stem-loop segment or ribosomal helix
      35, uniformly enriched in 13C and 15N, with RPCSA values measured at 5 and 25
      degrees C. Substantial cross-validated improvements in structural accuracy are
      obtained upon incorporation of RPCSA restraints.

PMID- 16881620
TI  - Iron-based layered superconductor: LaOFeP.
AB  - We report superconductivity in an iron-based layered oxy-pnictide LaOFeP. LaOFeP
      is composed of an alternate stack of lanthanum oxide (La3+O2-) and iron pnictide
      (Fe2+P3-) layers. Magnetic and electrical resistivity measurements verify the
      occurrence of the superconducting transition at approximately 4 K.

PMID- 16881621
TI  - Molecular architecture via coordination: self-assembly of nanoscale hexagonal
      metallodendrimers with designed building blocks.
AB  - The first self-assembly of nanoscale metallodendrimers that have a hexagonal
      cavity as a core via the directional-bonding approach is reported. All
      metallodendrimers were characterized by multinuclear NMR (1H and 31P), mass
      spectrometry (ESI-MS and ESI-FT-ICR), and elemental analysis.

PMID- 16881622
TI  - Two pressure-induced superconducting anion radical salts exhibiting different
      spin states at ambient pressure.
AB  - Pressure-induced superconducting behavior was found in two anion radical salts,
      EtMe3Z[Pd(dmit)2]2 (dmit = 1,3-dithiole-2-thione-4,5-dithiolate, Z = P, As), that
      are Mott insulators and exhibit different magnetic and structural transitions at
      ambient pressure.

PMID- 16881623
TI  - Nanoparticle-based sensing of glycan-lectin interactions.
AB  - Here we present the first report on nanoparticle-based biosensing of glycan
      markers of diseases. The protocol relies on the competition between a nanocrystal
      (CdS)-tagged sugar and the target sugar for the binding sites of surface-confined
      lectin and monitoring the extent of competition through highly sensitive
      electrochemical detection of the captured nanocrystal. This development is
      expected to allow decentralized detection of carbohydrate moieties and lectin
      carbohydrate interactions to be performed more rapidly, sensitively,
      inexpensively, and reliably.

PMID- 16881624
TI  - Thermal reactions of 7-d- and 8-d-bicyclo[4.2.0]oct-2-enes.
AB  - The gas phase thermal reactions exhibited by bicyclo[4.2.0]oct-2-ene and 7-d and
      8-d analogues at 300 degrees C have been followed kinetically through GC and 2H
      NMR spectroscopic analyses. In contrast to the pattern of transformations
      exhibited by bicyclo[3.2.0]hept-2-ene and deuterium-labeled analogues, no
      reactions initiated by C1-C6 bond cleavage are seen, epimerization at C8 is much
      faster than [1,3] shifts leading to bicyclo[2.2.2]oct-2-ene, and the ratio of
      rate constants for [1,3] carbon migration with inversion versus migration with
      retention is approximately 1.4. Homolysis of C1-C8 to give a conformationally
      flexible diradical intermediate having a relatively long lifetime and multiple
      options for further reaction (re-formation of C1-C8 with or without net
      epimerization, fragmentation to 1,3-cyclohexadiene and ethylene, migration to the
      original C3 with inversion or retention) accords well with the observations.
      Clearly, orbital symmetry control does not govern stereochemistry for the [1,3]
      sigmatropic carbon shifts.

PMID- 16881625
TI  - Sensitive and selective detection of nitric oxide using an H-NOX domain.
AB  - Tt Y140F, a mutant of the H-NOX (Heme-Nitric Oxide or OXygen binding domain)
      protein from Thermoanaerobacter tengcongensis, is presented as a novel
      genetically encoded NO sensor. Tt Y140F is easily purified and obtained in high
      yields from standard E. coli expression systems. It is extremely stable as both
      the ferrous unligated and ferrous-nitrosyl complexes in air over a range of
      temperatures (up to 70 degrees C) without oxidizing, denaturing, or binding O2.
      NO binding is quantitative and can be followed using simple absorbance
      spectroscopy. In theory, NO concentrations between 300 nM and 30 muM can be
      accurately and easily detected.

PMID- 16881626
TI  - Nanoscale spherical architectures fabricated by metal coordination of multiple
      dipyrrin moieties.
AB  - Phenylethynyl-bridged dipyrrin "dimers" have performed ZnII complexation to give
      coordination polymers, which provided the fluorescent colloidal spherical objects
      in solution as well as on the substrate according to the spacer units. Using a
      mixture of THF and water, unique morphologies, such as bell-shaped and "golf
      ball"-like architectures, were observed.

PMID- 16881627
TI  - Carbons with extremely large volume of uniform mesopores synthesized by
      carbonization of phenolic resin film formed on colloidal silica template.
AB  - Mesoporous carbons with extremely large pore volume ( approximately 6 cm3/g) and
      narrow bimodal pore size distribution were synthesized by using 24 nm silica
      colloids as template.

PMID- 16881629
TI  - Hydration and dynamic behavior of poly(N-isopropylacrylamide)s in aqueous
      solution: a sharp phase transition at the lower critical solution temperature.
AB  - The number of hydrated water molecules per poly(N-isopropylacrylamide) monomer
      unit in homogeneous aqueous solution was determined to be 11 exactly and anew
      below the lower critical solution temperature of 32 degrees C employing high
      frequency dielectric relaxation techniques.

PMID- 16881628
TI  - Palladium-catalyzed coupling of ammonia and lithium amide with aryl halides.
AB  - A mild, palladium-catalyzed coupling of aryl halides with ammonia or lithium
      amide to form primary arylamines as the major product is described. These
      reactions occurred with excellent selectivity for formation of the primary
      arylamine over formation of the diarylamine (9.5:1 to over 50:1 ratios of
      arylamine to diarylamine). In addition, the first organopalladium complex with a
      terminal -NH2 ligand has been isolated. This complex reductively eliminates to
      form arylamines.

PMID- 16881630
TI  - Dodecamethoxy- and hexaoxotricyclobutabenzene: synthesis and characterization.
AB  - We report herein the syntheses of dodecamethoxytricyclobutabenzene (TCBB) 1 and
      hexaoxo-TCBB 2, a class of molecules with structural and theoretical interest.
      The preparation is based on the 3-fold [2 + 2] cycloadditions of benzyne and
      ketene silyl acetals (KSAs), where the selectively protected 2-iodophloroglucinol
      derivative served as a synthetic equivalent of benztriyne I, allowing rapid and
      regioselective annulation of fully functionalized four-membered rings. Structural
      study on the former compound showed that the C-C bond lengths in the central
      benzene ring were essentially the same.

PMID- 16881631
TI  - Revealing two-state protein-protein interactions of calmodulin by single-molecule
      spectroscopy.
AB  - We report a single-molecule fluorescence resonance energy transfer (FRET) and
      polarization study of conformational dynamics of calmodulin (CaM) interacting
      with a target peptide, C28W of a 28 amino acid oligomer. The C28W peptide
      represents the essential binding sequence domain of the Ca-ATPase protein
      interacting with CaM, which is important in cellular signaling for the regulation
      of energy in metabolism. However, the mechanism of the CaM/C28W recognition
      complex formation is still unclear. The amino-terminal (N-terminal) domain of the
      CaM was labeled with a fluorescein-based arsenical hairpin binder (FlAsH) that
      enables our unambiguous probing of the CaM N-terminal target-binding domain
      motions on a millisecond time scale without convolution of the probe-dye random
      motions. By analyzing the distribution of FRET efficiency between FlAsH labeled
      CaM and Texas Red labeled C28W and the polarization fluctuation dynamics and
      distributions of the CaM N-terminal domain, we reveal binding-unbinding motions
      of the N-terminal domain of the CaM in CaM/C28W complexes, which is strong
      evidence of a two-state binding interaction of CaM-mediated cell signaling.

PMID- 16881632
TI  - Chemical control of electronic structure and superconductivity in layered borides
      and borocarbides: understanding the absence of superconductivity in LixBC.
AB  - The synthetic search for materials related to the 39 K superconductor MgB2 has
      been difficult. The most promising theoretical suggestion, hole doping of LiBC,
      does not lead to a new superconductor. We show here that a combination of density
      functional theory (DFT) calculations, materials synthesis, and structural
      characterization reveals the origin of the puzzling absence of superconductivity
      in Li1/2BC as a subtle change in the electronic structure driven by structural
      response to the introduction of holes. This indicates that the unique aspects of
      the electronic structure of MgB2 will be demanding to replicate in other systems.

PMID- 16881633
TI  - Structural characterization of ultrasmall superparamagnetic iron oxide (USPIO)
      particles in aqueous suspension by energy dispersive X-ray diffraction (EDXD).
AB  - Ultrasmall superparamagnetic iron oxide (USPIO) particles were structurally
      characterized in situ in an aqueous dilute suspension by energy dispersive X-ray
      diffraction (EDXD) and ex situ as powders obtained by lyophilization of the
      suspension by angular dispersive X-ray diffraction (ADXD) at 20 degrees C.
      Structural parameters obtained by the Rietveld method on ADXD data were used as
      starting parameters for modeling the structure of the particles in suspension.
      Although each particle is a single crystal, as evidenced by conventional X-ray
      diffraction, our results indicate that the structural order, specific to a
      crystal, does not extend to the entire volume of the particle. In fact, each
      individual particle, averagely, has a crystalline structural extension ca. 4.0 nm
      smaller than the apparent dimensions obtained by both ADXD and TEM (ca. 8.0 nm).

PMID- 16881634
TI  - Zero-point corrections and temperature dependence of HD spin-spin coupling
      constants of heavy metal hydride and dihydrogen complexes calculated by
      vibrational averaging.
AB  - Vibrational corrections (zero-point and temperature dependent) of the H-D spin
      spin coupling constant J(HD) for six transition metal hydride and dihydrogen
      complexes have been computed from a vibrational average of J(HD) as a function of
      temperature. Effective (vibrationally averaged) H-D distances have also been
      determined. The very strong temperature dependence of J(HD) for one of the
      complexes, [Ir(dmpm)Cp*H2]2 + (dmpm = bis(dimethylphosphino)methane) can be
      modeled simply by the Boltzmann average of the zero-point vibrationally averaged
      JHD of two isomers. For this complex and four others, the vibrational corrections
      to JHD are shown to be highly significant and lead to improved agreement between
      theory and experiment in most cases. The zero-point vibrational correction is
      important for all complexes. Depending on the shape of the potential energy and J
      coupling surfaces, for some of the complexes higher vibrationally excited states
      can also contribute to the vibrational corrections at temperatures above 0 K and
      lead to a temperature dependence. We identify different classes of complexes
      where a significant temperature dependence of J(HD) may or may not occur for
      different reasons. A method is outlined by which the temperature dependence of
      the HD spin-spin coupling constant can be determined with standard quantum
      chemistry software. Comparisons are made with experimental data and previously
      calculated values where applicable. We also discuss an example where a low-order
      expansion around the minimum of a complicated potential energy surface appears
      not to be sufficient for reproducing the experimentally observed temperature
      dependence.

PMID- 16881635
TI  - Layering at an ionic liquid-vapor interface: a molecular dynamics simulation
      study of [bmim][PF6].
AB  - The structure of the planar liquid-vapor interface of a room-temperature ionic
      liquid, 1-n-butyl-3-methylimidazolium hexafluorophosphate ([bmim][PF6]), is
      studied using atomistic molecular dynamics simulations. Layering of the ions at
      the interface is observed as oscillations in the corresponding number density
      profiles. These oscillations, however, are diminished in amplitude in the
      electron density profile, due to a near cancellation in the contributions from
      the anions and the cations. An enhancement by 12% in the electron density at the
      interface over its value in the bulk liquid is observed, in excellent agreement
      with X-ray reflectivity experiments. The anions are found to predominantly
      contribute to this increase in the interfacial electron density. The cations
      present at the interface are oriented anisotropically. Their butyl chains are
      observed to be preferentially oriented along the interface normal and to project
      outside the liquid surface, thus imparting a hydrophobic character. In the
      densest region of the interface, the imidazolium ring plane is found to lie
      parallel to the surface normal, in agreement with direct recoil spectroscopy
      experiments.

PMID- 16881636
TI  - Facile interstrand migration of the hydrocarbon moiety of a dibenzo[a,l]pyrene
      11,12-diol 13,14-epoxide adduct at N2 of deoxyguanosine in a duplex
      oligonucleotide.
AB  - When a synthesized deoxyribonucleotide duplex, 5'-CCATCGCTACC-3'.5'-GGTAGCGATGG
      3', containing a trans 14R dibenzo[a,l]pyrene (DB[a,l]P) adduct, corresponding to
      trans opening of the (+)-(11S,12R)-diol (13R,14S)-epoxide by N (2) of the central
      G residue, was allowed to stand for 2-6 days at ambient temperature in neutral
      aqueous solution, three new products were observed on denaturing HPLC. One of
      these corresponded to loss of the DB[a,l]P moiety from the original adducted
      strand to give an 11-mer with an unmodified central dG. The other two products
      resulted from a highly unexpected migration of the hydrocarbon moiety to either
      dG5 or dG7 of the complementary strand, 5'-GGTAG5CG7ATGG-3'. Enzymatic hydrolysis
      of the two 11-mer migration products followed by CD spectroscopy of the isolated
      adducted nucleosides indicated that, in both cases, the hydrocarbon moiety had
      undergone configurational inversion at C14 to give the cis 14S DB[a,l]P dG
      adduct. MS/MS and partial enzymatic hydrolysis showed that the major 11-mer had
      the hydrocarbon at dG7. Two 11-mer oligonucleotides were synthesized with a
      single cis 14S DB[a,l]P dG adduct either at G7 or at G5 and were found to be
      chromatographically identical to the major and minor migration products,
      respectively. Although HPLC evidence suggested that a small extent of hydrocarbon
      migration from the trans 14S DB[a,l]P dG diastereomer also occurred, the very
      small amount of presumed migration products from this isomer precluded their
      detailed characterization. This interstrand migration appears unique to DB[a,l]P
      adducts and has not been observed for their fjord-region benzo[c]phenanthrene or
      bay-region benzo[a]pyrene analogues.

PMID- 16881638
TI  - A comparative QM/MM simulation study of the reaction mechanisms of human and
      Plasmodium falciparum HG(X)PRTases.
AB  - QM/MM hybrid potential free-energy simulations are performed to compare the
      reaction mechanisms of human hypoxanthine guanine phosphoribosyl transferase
      (HGPRTase) and the corresponding enyzme from Plasmodium falciparum (Pf),
      hypoxanthine guanine xanthine phosphoribosyl transferase (HGXPRTase). These
      enzymes share 44% of sequence identity but display very different affinities for
      xanthine. The calculations show that in both enzymes phosphoribosyl transfer
      proceeds via a dissociative mechanism from an anionic form of the substrate.
      Nevertheless, there are significant differences in the geometries of critical
      structures along the reaction paths which it may be possible to exploit for the
      design of specific inhibitors against the Pf enzyme.

PMID- 16881639
TI  - Wheel-shaped polyoxotungstate [Cu20Cl(OH)24(H2O)12(P8W48O184)]25- macroanions
      form supramolecular "blackberry" structure in aqueous solution.
AB  - The hydrophilic polyoxotungstate [Cu20Cl(OH)24(H2O)12(P8W48O184)]25-
      ({Cu20P8W48}) self-assembles into single-layer, hollow, spherical "blackberry"
      type structures in aqueous solutions, as studied by dynamic light scattering
      (DLS), static light scattering (SLS), zeta potential analysis, and scanning
      electron microscopy (SEM) techniques. This represents the first report of
      blackberry formation for a non-Mo-containing polyoxometalate. There is no obvious
      change in the shape and size of the blackberries during the slow blackberry
      formation process, neither with macroionic concentration nor with temperature.
      Our results suggest that the blackberry-type structure formation is most likely a
      general phenomenon for hydrophilic macroions with suitable size and charge in a
      polar solvent, and not a specific property of polyoxomolybdates and their
      derivatives. The {Cu20P8W48} macroions are thus far the smallest type of
      macroions to date (equivalent radius < 2 nm) showing the unique self-assembly
      behavior, helping us to move one step closer toward identifying the transition
      point from simple ions (can be described by the Debye-Huckel theory) to macroions
      in very dilute solutions. Moreover, by using {Cu20P8W48} blackberry-type
      structures as the model system, the electrophoretic properties of macroionic
      supramolecular structures are studied for the first time via zeta-potential
      analysis. The mobility of blackberry-type structures is determined and used for
      understanding the state of small cations in solution. We notice that the average
      charge density on each {Cu20P8W48} macroanion in a blackberry is much lower than
      that of discrete "free" {Cu20P8W48} macroions. This result suggests that some
      small alkali counterions are closely associated with, or even incorporated into,
      the blackberry-type structures and thus do not contribute to solution
      conductivity. This model is fully consistent with our speculation that monovalent
      counterions play an important role in the self-assembly of macroions, possibly
      providing an attractive force contributing to blackberry formation.

PMID- 16881640
TI  - Self-assembly of peptide scaffolds in biosilica formation: computer simulations
      of a coarse-grained model.
AB  - The self-assembly of model peptides is studied using Brownian dynamics computer
      simulations. A coarse-grained, bead-spring model is designed to mimic silaffins,
      small peptides implicated in the biomineralization of certain silica diatom
      skeletons and observed to promote the formation of amorphous silica nanospheres
      in vitro. The primary characteristics of the silaffin are a 15 amino acid
      hydrophilic backbone and two modified lysine residues near the ends of the
      backbone carrying long polyamine chains. In the simulations, the model peptides
      self-assemble to form spherical clusters, networks of strands, or bicontinuous
      structures, depending on the peptide concentration and effective temperature. The
      results indicate that over a broad range of volume fractions (0.05-25%) the
      characteristic structural lengthscales fall in the range 12-45 nm. On this basis,
      we suggest that self-assembled structures act as either nucleation points or
      scaffolds for the deposition of 10-100 nm silica-peptide building blocks from
      which diatom skeletons and synthetic nanospheres are constructed.

PMID- 16881641
TI  - Two-phase synthesis of shape-controlled colloidal zirconia nanocrystals and their
      characterization.
AB  - We have developed a two-phase approach for the synthesis of shape-controlled
      colloidal zirconia nanocrystals, including spherical-, teardrop-, rod-, and rice
      grain-shaped particles. We found that the key factors for controlling the shape
      were the reaction time, the nature of the capping agent, and the monomer
      concentration. We have analyzed the morphologies, crystallinity, optical
      properties, and structural features of the as-prepared ZrO2 nanoparticles by
      using transmission electron microscopy (TEM), high-resolution TEM, X-ray powder
      diffraction, and UV-vis absorption and fluorescence spectroscopy. The possible
      nucleation and growth process is also discussed.

PMID- 16881637
TI  - Base-displaced intercalated structure of the food mutagen 2-amino-3
      methylimidazo[4,5-f]quinoline in the recognition sequence of the NarI restriction
      enzyme, a hotspot for -2 bp deletions.
AB  - The solution structure of the oligodeoxynucleotide 5'-d(CTCGGCXCCATC)-3'.5'
      d(GATGGCGCCGAG)-3' containing the heterocyclic amine 8-[(3-methyl-3H-imidazo[4,5
      f]quinolin-2-yl)amino]-2'-deoxyguanosine adduct (IQ) at the third guanine in the
      NarI restriction sequence, a hot spot for -2 bp frameshifts, is reported.
      Molecular dynamics calculations restrained by distances derived from 24 (1)H NOEs
      between IQ and DNA, and torsion angles derived from (3)J couplings, yielded
      ensembles of structures in which the adducted guanine was displaced into the
      major groove with its glycosyl torsion angle in the syn conformation. One proton
      of its exocyclic amine was approximately 2.8 A from an oxygen of the 5'
      phosphodiester linkage, suggesting formation of a hydrogen bond. The carcinogen
      guanine linkage was defined by torsion angles alpha' [N9-C8-N(IQ)-C2(IQ)] of 159
      +/- 7 degrees and beta' [C8-N(IQ)-C2(IQ)-N3(IQ)] of -23 +/- 8 degrees . The
      complementary cytosine was also displaced into the major groove. This allowed IQ
      to intercalate between the flanking C.G base pairs. The disruption of Watson
      Crick hydrogen bonding was corroborated by chemical-shift perturbations for base
      aromatic protons in the complementary strand opposite to the modified guanine.
      Chemical-shift perturbations were also observed for (31)P resonances
      corresponding to phosphodiester linkages flanking the adduct. The results
      confirmed that IQ adopted a base-displaced intercalated conformation in this
      sequence context but did not corroborate the formation of a hydrogen bond between
      the IQ quinoline nitrogen and the complementary dC [Elmquist, C. E.; Stover, J.
      S.; Wang, Z.; Rizzo, C. J. J. Am. Chem. Soc. 2004, 126, 11189-11201].

PMID- 16881642
TI  - The mechanism of epoxide carbonylation by [Lewis Acid]+[Co(CO)4]- catalysts.
AB  - A detailed mechanistic investigation of epoxide carbonylation by the catalyst
      [(salph)Al(THF)2]+ [Co(CO)4]- (1, salph = N,N'-o-phenylenebis(3,5-di-tert
      butylsalicylideneimine), THF = tetrahydrofuran) is reported. When the
      carbonylation of 1,2-epoxybutane (EB) to beta-valerolactone is performed in 1,2
      dimethoxyethane solution, the reaction rate is independent of the epoxide
      concentration and the carbon monoxide pressure but first order in 1. The rate of
      lactone formation varies considerably in different solvents and depends primarily
      on the coordinating ability of the solvent. In mixtures of THF and cis/trans-2,5
      dimethyltetrahydrofuran, the reaction is first order in THF. From spectroscopic
      and kinetic data, the catalyst resting state was assigned to be the neutral (beta
      aluminoxy)acylcobalt species (salph)AlOCH(Et)CH2COCo(CO)4 (3a), which was
      successfully trapped with isocyanates. As the formation of 3a from EB, CO, and 1
      is rapid, lactone ring closing is rate-determining. The favorable impact of
      donating solvents was attributed to the necessity of stabilizing the aluminum
      cation formed upon generation of the lactone.

PMID- 16881643
TI  - Exploration of ground and excited electronic states of aromatic and quinoid S,S
      dioxide terthiophenes. Complementary systems for enhanced electronic organic
      materials.
AB  - We analyze the electronic and molecular structures for the ground and excited
      electronic states of aromatic terthiophene (3T), the quinodimethane 3',4'-dibutyl
      5,5' '-bis(dicyanomethylene)-5,5' '-dihydro-2,2':5',2' '-terthiophene (3Q), and
      isologues with the middle ring S-oxidized (3TO2, 3QO2). These represent extremes
      of electron rich and deficient ground states, often exhibiting complementary
      properties. Oxidizing the central sulfur atom affects the molecular structure,
      electron affinity, and photophysical properties of both pi systems. The
      consequences for 3T include de-aromatization of the central thiophene, red
      shifting of the electronic absorption spectrum, and lowering of the reduction
      potential. The electron deficient quinoid 3QO2 shows an enhancement of electron
      affinity from reducing the electron-donor ability of sulfur, and a blue-shifting
      of its electronic absorption spectrum was seen. Fluorescence emission is quenched
      in the sulfonated terthiophene, and the contrary effect again would be expected
      upon sulfonation of a quinoid emitter. Raman vibrational spectroscopy,
      electrochemistry, and UV-vis and fluorescence spectroscopies are analyzed in
      conjunction with theoretical calculations.

PMID- 16881644
TI  - How an enzyme tames reactive intermediates: positioning of the active-site
      components of lysine 2,3-aminomutase during enzymatic turnover as determined by
      ENDOR spectroscopy.
AB  - Lysine 2,3-aminomutase (LAM) utilizes a [4Fe-4S] cluster, S-adenosyl-L-methionine
      (SAM), and pyridoxal 5'-phosphate (PLP) to isomerize L-alpha-lysine to L-beta
      lysine. LAM is a member of the radical-SAM enzyme superfamily in which a [4Fe
      4S]+ cluster reductively cleaves SAM to produce the 5'-deoxyadenosyl radical,
      which abstracts an H-atom from substrate to form 5'-deoxyadenosine (5'-Ado) and
      the alpha-Lys* radical (state 3 (Lys*)). This radical isomerizes to the beta-Lys*
      radical (state 4(Lys*)), which then abstracts an H-atom from 5'-Ado to form beta
      lysine and the 5'-deoxyadenosyl radical; the latter then regenerates SAM. We use
      13C, 1,2H, 31P, and 14N ENDOR to characterize the active site of LAM in
      intermediate states that contain the isomeric substrate radicals or analogues.
      With L-alpha-lysine as substrate, we monitor the state with beta-Lys*. In
      parallel, we use two substrate analogues that generate stable analogues of the
      alpha-Lys* radical: trans-4,5-dehydro-L-lysine (DHLys) and 4-thia-L-lysine
      (SLys). This first glimpse of the motions of active-site components during
      catalytic turnover suggests a possible major movement of PLP during catalysis.
      However, the principal focus of this work is on the relative positions of the
      carbons involved in H-atom transfer. We conclude that the active site facilitates
      hydrogen atom transfer by enforcing van der Waals contact between radicals and
      their reacting partners. This constraint enables the enzyme to minimize and even
      eliminate side reactions of highly reactive species such as the 5'-deoxyadensosyl
      radical.

PMID- 16881645
TI  - Europium(III) macrocyclic complexes with alcohol pendant groups as chemical
      exchange saturation transfer agents.
AB  - Paramagnetic lanthanide(III) complexes that contain hyperfine-shifted
      exchangeable protons offer considerable advantages over diamagnetic molecules as
      chemical exchange saturation transfer (CEST) agents for MRI. As part of a program
      to investigate avenues to improve the sensitivity of such agents, the CEST
      characteristics of europium(III) macrocyclic complexes having appended
      hydroxyethyl groups were investigated. The CEST spectrum of the asymmetrical
      complex, EuCNPHC3+, shows five distinct peaks for each magnetically nonequivalent
      exchangeable proton in the molecule. The CEST spectra of this complex were fitted
      to NMR Bloch theory to yield exchange rates between each of six exchanging proton
      pools (five on the agent plus bulk water). Exchange between the Eu3+-bound
      hydroxyl protons and bulk water protons was slow in dry acetonitrile but
      accelerated incrementally upon stepwise addition of water. In pure water,
      exchange was too fast to observe a CEST effect. The utility of this class of
      europium(III) complex for CEST imaging applications is ultimately limited by the
      small chemical shifts induced by the hydroxyl-appended ligands of this type and
      the resulting small Deltaomega values for the exchangeable hydroxyl protons.

PMID- 16881646
TI  - Electrochemistry, spectroscopy, and electrogenerated chemiluminescence of silole
      based chromophores.
AB  - We studied the electrochemical and spectroscopic properties of a series of
      extended silole-based chromophores to understand the effect of structure on
      behavior. By changing the substituents attached to the chromophore, we observed
      large variations in luminescence quantum efficiency (ca. 0-0.6), lambdamax for
      absorbance and photoluminescence (PL), and radical ion stability. The differences
      are related to the motion in the 2,5-substituents and the steric protection of
      both the chromophore and the reactive parts of the substituents. For several
      compounds the electrogenerated chemiluminescence (ECL) spectrum was also compared
      to the photoluminescence spectrum. In all cases, the ECL lambdamax and the PL
      lambdamax were about the same.

PMID- 16881647
TI  - Manipulation of aqueous growth of CdTe nanocrystals to fabricate colloidally
      stable one-dimensional nanostructures.
AB  - The present article is devoted to systematically exploring the influence of
      various experimental variables, including the precursor concentration, the ligand
      nature, the counterion type, the Cd-to-Te molar ratio, pH, and temperature, on
      the aqueous growth of CdTe nanocrystals. The growth may be divided into two
      stages: the early fast growth stage and the later slow growth stage. The later
      stage is found to be dominated by Ostwald ripening (OR), being strongly dependent
      on all experimental conditions. In contrast, the early stage is dominated by
      adding monomers to nanocrystals, which may be dramatically accelerated by
      lowering precursor concentrations and using ligands with a molecular structure
      similar to that of thioglycolic acid (TGA). This fast growth stage is similar to
      that observed during organometallic growth of nanocrystals in hot organic media.
      On the basis of this finding, one-dimensional wurtzite CdTe nanostructures can be
      directly prepared in aqueous media by storing rather dilute precursor solution
      (2.4 mM with reference to ligand) in the presence of TGA at lower temperature
      (from room temperature to 80 degrees C). A low growth temperature is used to
      suppress OR during crystal growth. In addition, the simultaneous presence of both
      TGA-like ligand and 1-thioglycerol or 2-mercaptoethylamine leads to formation of
      colloidally stable 1D CdTe nanostructures with controlled aspect ratios.

PMID- 16881649
TI  - Ferromagnetic coupling in hexanuclear gadolinium clusters.
AB  - The magnetic susceptibilities of hexanuclear gadolinium clusters in the compounds
      Gd(Gd6ZI12) (Z = Co, Fe, or Mn) and CsGd(Gd6CoI12)2 are reported and subjected to
      theoretical analysis with the help of density functional theory (DFT)
      computations. The single-crystal structure of Gd(Gd6CoI12) is reported here as
      well. We find that the compound with a closed shell of cluster bonding electrons,
      Gd(Gd6CoI12), exhibits the effects of antiferromagnetic coupling over the entire
      range of temperatures measured (4-300 K). Clusters with unpaired, delocalized
      cluster bonding electrons (CBEs) exhibit enhanced susceptibilities consistent
      with strong ferromagnetic coupling, except at lower temperatures (less than 30 K)
      where intercluster antiferromagnetic coupling suppresses the susceptibilities.
      The presence of two unpaired CBEs, as in [Gd6MnI12]3-, yields stronger coupling
      than when just one unpaired CBE is present, as in [Gd6FeI12]3- or [Gd6CoI12]2-.
      DFT calculations on model molecular systems, [Gd6CoI12](OPH3)6 and
      [Gd6CoI12]2(OPH3)10, indicate that the delocalized cluster bonding electrons are
      highly effective at mediating intracluster ferromagnetic exchange coupling
      between the Gd atom 4f7 moments and that intercluster coupling is expected to be
      antiferromagnetic. The DFT calculations were used to calculate the relative
      energies of various 4f7 spin patterns and form the basis for construction of a
      simple spin Hamiltonian describing the coupling within the [Gd6CoI12] cluster.

PMID- 16881648
TI  - Mossbauer and computational study of an N2-bridged diiron diketiminate complex:
      parallel alignment of the iron spins by direct antiferromagnetic exchange with
      activated dinitrogen.
AB  - This work reports Mossbauer and DFT studies of the diiron-N2 complex LMeFeNNFeLMe
      (L = beta-diketiminate), 1a. Complex 1a, formally diiron(I), has a system spin S
      = 3 with an isolated MS = +/-3 quasi-doublet as a ground state; the MS = +/-2
      doublet is >100 cm-1 higher in energy. Complex 1a exhibits at 4.2 K a large,
      positive magnetic hyperfine field, Bint = +68.1 T, and an effective g value of 16
      +/- 2 along the easy magnetization axis of the ground doublet; this value is
      significantly larger than the spin-only value (g = 12). These results have been
      rationalized by DFT calculations, which show that each Fe site donates
      significant electron density into the pi* orbitals of dinitrogen, resulting in a
      configuration best described as two high-spin FeII (Sa = Sb = 2) bridged by
      triplet N22- (Sc = 1). In this description the minority spin electron of each
      iron is accommodated by two nonbonding, closely spaced 3d orbitals, z2 and yz (z
      is perpendicular to the diketiminate planes, x is along the Fe...Fe vector). Spin
      orbit coupling between these orbital states generates a large unquenched orbital
      momentum along the iron-iron vector. The S = 3 ground state of 1a results from
      strong antiferromagnetic direct exchange couplings of the Fe spins (Sa = Sb = 2)
      to the N22- spin (Sc = 1) and can be formulated as ((Sa,Sb)Sab = 4, Sc = 1), S =
      3>; H = J(Sa + Sb).Sc with J approximately 3500 cm-1.

PMID- 16881650
TI  - Evidence for increased exchange interactions with 5d compared to 4d metal ions.
      Experimental and theoretical insights into the ferromagnetic interactions of a
      series of trinuclear [{M(CN)8}3-/NiII] compounds (M = MoV or WV).
AB  - Two main questions are addressed in this study: (i) What increase of exchange
      interaction can be expected when replacing a paramagnetic metal ion with a
      heavier congener located farther down the periodic table (i.e., 3d-4d-5d), and
      (ii) for a molecular unit with higher coordination numbers, eight in the present
      case, how is the magnetic information transferred from the metal ion to its
      ligand set? Qualitative and quantitative investigations on a series of
      trimetallic cyano-bridged {MoV(CN)8-NiII} and {WV(CN)8-NiII} compounds revealed
      ferromagnetic interactions but with a strength modulated by the spin organization
      and their nature. DFT calculations have been used to examine the mechanism and
      strengths of the exchange coupling, as well as the influence of the local
      symmetry of the cyanometalate unit on the spin density distribution. Both the
      experimental and the calculated behaviors underline a noticeable difference
      between the Mo and the W derivatives (JMoNi = 26.9 cm(-1) and JWNi = 37.3 cm(-1))
      that is correlated to the spin density transferred from the metal center to its
      ligand set. It is also shown that the shape of the {M(CN)8} polyhedron may lead
      to nonequivalent CN sites and, consequently, to different strengths of the
      exchange interaction as a result of the position of the bridging ligands.

PMID- 16881651
TI  - Importance of direct spin-spin coupling and spin-flip excitations for the zero
      field splittings of transition metal complexes: a case study.
AB  - This work reports the evaluation of several theoretical approaches to the zero
      field splitting (ZFS) in transition metal complexes. The experimentally well
      known complex [Mn(acac)3] is taken as an example. The direct spin-spin
      contributions to the ZFS have been calculated on the basis of density functional
      theory (DFT) or complete active space self-consistent field (CASSCF) wave
      functions and have been found to be much more important than previously assumed.
      The contributions of the direct term may exceed approximately 1 cm(-1) in
      magnitude and therefore cannot be neglected in any treatment that aims at a
      realistic quantitative modeling of the ZFS. In the DFT framework, two different
      variants to treat the spin-orbit coupling (SOC) term have been evaluated. The
      first approach is based on previous work by Pederson, Khanna, and Kortus, and the
      second is based on a "quasi-restricted" DFT treatment which is rooted in our
      previous work on ZFS. Both approaches provide very similar results and
      underestimate the SOC contribution to the ZFS by a factor of 2 or more. The SOC
      is represented by an accurate multicenter spin-orbit mean-field (SOMF)
      approximation which is compared to the popular effective DFT potential-derived
      SOC operator. In addition to the DFT results, direct "infinite order" ab initio
      calculations of the SOC contribution to the ZFS based on CASSCF wave functions,
      the spectroscopy-oriented configuration interaction (SORCI), and the difference
      dedicated CI (DDCI) approach are reported. In general, the multireference ab
      initio results provide a more realistic description of the ZFS in [Mn(acac)3].
      The conclusions likely carry over to many other systems. This is attributed to
      the explicit treatment of the multiplet effects which are of dominant importance,
      since the calculations demonstrate that, even in the high-spin d4 system MnIII,
      the spin-flip excitations make the largest contribution to the SOC. It is
      demonstrated that the ab initio methods can be used even for somewhat larger
      molecules (the present calculations were done with more than 500 basis functions)
      in a reasonable time frame. Much more economical but still fairly reasonable
      results have been achieved with the INDO/S treatment based on CASSCF and SOC-CI
      wave functions.

PMID- 16881652
TI  - MIL-96, a porous aluminum trimesate 3D structure constructed from a hexagonal
      network of 18-membered rings and mu3-oxo-centered trinuclear units.
AB  - A new aluminum trimesate Al12O(OH)18(H2O)3(Al2(OH)4)[btc]6.24H2O, denominated MIL
      96, was synthesized under mild hydrothermal conditions (210 degrees C, 24 h) in
      the presence of 1,3,5-benzenetricarboxylic acid (trimesic acid or H3btc) in
      water. Hexagonal crystals, allowing a single-crystal XRD analysis, are grown from
      a mixture of trimethyl 1,3,5-benzenetricarboxylate (Me3btc), HF, and TEOS. The
      MIL-96 structure exhibits a three-dimensional (3D) framework containing isolated
      trinuclear mu3-oxo-bridged aluminum clusters and infinite chains of AlO4(OH)2 and
      AlO2(OH)4 octahedra forming a honeycomb lattice based on 18-membered rings. The
      two types of aluminum groups are connected to each other through the trimesate
      species, which induce corrugated chains of aluminum octahedra, linked via mu2
      hydroxo bonds with the specific -cis-cis-trans- sequence. The 3D framework of MIL
      96 reveals three types of cages. Two of them, centered at the special positions 0
      0 0 and 2/3 1/3 1/4, have estimated pore volumes of 417 and 635 A3, respectively,
      and encapsulate free water molecules. The third one has a smaller pore volume and
      contains disordered aluminum octahedral species (Al(OH)6). The solid-state NMR
      characterization is consistent with crystal structure and elemental and thermal
      analyses. The four aluminum crystallographic sites are resolved by means of 27Al
      3QMAS technique. This product is able to sorb both carbon dioxide and methane at
      room temperature (4.4 mmol.g(-1) for CO2 and 1.95 mmol.g(-1) for CH4 at 10 bar)
      and hydrogen at 77 K (1.91 wt % under 3 bar).

PMID- 16881653
TI  - Synthesis and photophysical properties of borondipyrromethene dyes bearing aryl
      substituents at the boron center.
AB  - Several borondipyrromethene (Bodipy) dyes bearing an aryl nucleus linked directly
      to the boron center have been prepared under mild conditions. The choice of
      Grignard or lithio organo-metallic reagents allows the isolation of B(F)(aryl) or
      B(aryl)2 derivatives; where aryl refers to phenyl, anisyl, naphthyl, or pyrenyl
      fragments. A single crystal, X-ray structure determination for the bis-anisyl
      compound shows that the sp3 hybridized boron center remains pseudo-tetrahedral
      and that the B-C bond distances are 1.615 and 1.636 A. All compounds are
      electrode active but replacement of the fluorine atoms by aryl fragments renders
      the Bodipy unit more easily oxidized by 100 mV in the B(F)(aryl) and 180 mV in
      the B(aryl)2 compounds whereas reduction is made more difficult by a comparable
      amount. Strong fluorescence is observed from the Bodipy fluorophore present in
      each of the new dyes, with the radiative rate constant being independent of the
      nature of the aryl substituent. The fluorescence quantum yields are solvent
      dependent and, at least in some cases (aryl = anisyl or pyrenyl), nonradiative
      decay from the first-excited singlet state is strongly activated. There is no
      indication, however, for population of a charge-transfer state, in which the aryl
      substituent acts as donor and the Bodipy fragment functions as acceptor, that is
      strongly coupled to the ground state. Instead, it is conjectured that
      nonradiative decay involves a conformational change driven by the solvophobic
      effect. Thus, the rate of nonradiative decay in any given solvent increases with
      increasing surface accessibility (or molar volume) of the aryl substituent.
      Intramolecular energy transfer from pyrene or naphthalene residues to Bodipy is
      quantitative.

PMID- 16881654
TI  - Supramolecular catalysis of unimolecular rearrangements: substrate scope and
      mechanistic insights.
AB  - A cavity-containing metal-ligand assembly is employed as a catalytic host for the
      3-aza Cope rearrangement of allyl enammonium cations. Upon binding, the rates of
      rearrangement are accelerated for all substrates studied, up to 850-fold.
      Activation parameters were measured for three enammonium cations in order to
      understand the origins of acceleration. Those parameters reveal that the
      supramolecular structure is able to reduce both the entropic and enthalpic
      barriers for rearrangement and is highly sensitive to small structural changes of
      the substrate. The space-restrictive cavity preferentially binds closely packed,
      preorganized substrate conformations, which resemble the conformations of the
      transition states. This hypothesis is also supported by quantitative NOE studies
      of two encapsulated substrates, which place the two reacting carbon atoms in
      close proximity. The capsule can act as a true catalyst, since release and
      hydrolysis facilitate catalytic turnover. The question of product hydrolysis was
      addressed through detailed kinetic studies. We conclude that the iminium product
      must dissociate from the cavity interior and the assembly exterior before
      hydroxide-mediated hydrolysis, and propose the intermediacy of a tight ion pair
      of the polyanionic host with the exiting product.

PMID- 16881655
TI  - Controlling the biological effects of spermine using a synthetic receptor.
AB  - Polyamines play an important role in biology, yet their exact function in many
      processes is poorly understood. Artificial host molecules capable of sequestering
      polyamines could be useful tools for studying their cellular function. However,
      designing synthetic receptors with affinities sufficient to compete with
      biological polyamine receptors remains a huge challenge. Binding affinities of
      synthetic hosts are typically separated by a gap of several orders of magnitude
      from those of biomolecules. We now report that a dynamic combinatorial selection
      approach can deliver a synthetic receptor that bridges this gap. The selected
      receptor binds spermine with a dissociation constant of 22 nM, sufficient to
      remove it from its natural host DNA and reverse some of the biological effects of
      spermine on the nucleic acid. In low concentrations, spermine induces the
      formation of left-handed DNA, but upon addition of our receptor, the DNA reverts
      back to its right-handed form. NMR studies and computer simulations suggest that
      the spermine complex has the form of a pseudo-rotaxane. The spermine receptor is
      a promising lead for the development of therapeutics or molecular probes for
      elucidating spermine's role in cell biology.

PMID- 16881656
TI  - A simple gamma-backbone modification preorganizes peptide nucleic acid into a
      helical structure.
AB  - Peptide nucleic acid (PNA) is a synthetic analogue of DNA and RNA, developed more
      than a decade ago in which the naturally occurring sugar phosphate backbone has
      been replaced by the N-(2-aminoethyl) glycine units. Unlike DNA or RNA in the
      unhybridized state (single strand) which can adopt a helical structure through
      base-stacking, although highly flexible, PNA does not have a well-defined
      conformational folding in solution. Herein, we show that a simple backbone
      modification at the gamma-position of the N-(2-aminoethyl) glycine unit can
      transform a randomly folded PNA into a helical structure. Spectroscopic studies
      showed that helical induction occurs in the C- to N-terminal direction and is
      sterically driven. This finding has important implication not only on the future
      design of nucleic acid mimics but also on the design of novel materials, where
      molecular organization and efficient electronic coupling are desired.

PMID- 16881657
TI  - Theoretical characterization of cyclic thiolated gold clusters.
AB  - The density functional theory is used to explore structural, energetic,
      vibrational, and optical properties of thiolated gold clusters (MeSAu)x with x =
      2-12. Clusters up to (MeSAu)4 adopt Au-S ring conformations, and crownlike
      structures are formed for larger sizes. The clusters are essentially polymeric
      and show convergence in structural and energetic properties at (MeSAu)4. The
      nature of the Au-S bond is polar covalent with a degree of cyclic electron
      delocalization. Vibrational analysis reveals characteristic Au-S stretch
      vibrations at approximately 300 cm(-1). Effects of ligand substitution are
      studied in the case of the tetramer by comparing the results for methylthiolate
      with hexylthiolate, benzenethiolate, and glutathionate (GS). The choice of ligand
      has clear effects on electronic properties. For example, the optical gap is
      approximately 1.5 eV lower for (GSAu)4 than for (MeSAu)4.

PMID- 16881658
TI  - Kinetically controlled catalytic formation of zinc oxide thin films at low
      temperature.
AB  - We developed a unique method to produce ZnO thin films by kinetically controlled
      catalytic hydrolysis of a molecular precursor at low temperature, operating in
      conjunction with the vectorial control of crystal growth. Using a system in which
      the diffusion of a volatile catalyst into a solution of molecular precursor of
      the metal oxide limits the rate of hydrolysis and establishes a gradient of
      catalyst concentration, we investigated the nucleation of textured nanoparticles
      at the gas-liquid interface and characterized their subsequent growth. Use of
      this slow diffusion method combined with prediction of molecular species using a
      partial charge model enables a higher level of organizational control than
      obtained in other low-temperature synthesis methods, without the use of organic
      molecules. Various metal oxides and their morphologies and chemical compositions
      can be tailored for specific applications using this relatively simple approach.

PMID- 16881659
TI  - Shape-specific detection based on fluorescence resonance energy transfer using a
      flexible water-soluble conjugated polymer.
AB  - We present the detection of the shape-specific conformation of DNA based on the
      fluorescence resonance energy transfer (FRET) by using a novel flexible water
      soluble cationic conjugated polymer (CCP). The flexible backbone of CCP has more
      conformational freedom with the potential to be responsive to analyte shape by
      electrostatic interaction between flexible CCP and negatively charged DNA. The
      analyte shape dependent recognition is accomplished by structural changes that
      compressed or extended the flexible CCP. The morphology-dependent spectral
      properties of the novel flexible polymer related to the analyte shapes are
      investigated in detail, where two types of chromophores, referred to as
      "isolated" segment and "packed" segment aggregates, within the flexible polymer
      are identified by means of ensemble and single molecule measurements upon binding
      with different geometric DNA. The change in fluorescence intensity upon binding
      with shape-specific DNA without obvious color shifts makes this novel flexible
      polymer a suitable CCP donor for FRET measurements. The results provide insights
      for understanding the spectral properties of flexible water-soluble CCP and
      CCP/DNA interaction related to the geometry of target analyte.

PMID- 16881660
TI  - Biocatalytic synthesis of a nanostructured and crystalline bimetallic perovskite
      like barium oxofluorotitanate at low temperature.
AB  - Silicatein, an enzymatic biocatalyst from the marine sponge Tethya aurantia, is
      demonstrated to catalyze and template the hydrolysis/condensation of the
      molecular precursor BaTiF6 at low temperature to form nanocrystalline BaTiOF4, an
      orthorhombic oxofluorotitanate. The kinetics of hydrolysis and growth were
      studied in-situ via pH profiling and quartz crystal microbalance (QCM)
      techniques. The composition and structure of the resulting BaTiOF4
      microstructures on the silicatein surface were characterized using FT-IR
      spectroscopy, X-ray photoelectron spectroscopy, energy-dispersive X-ray
      spectroscopy, scanning electron microscopy, transmission electron microscopy, and
      selected area electron diffraction. The silicatein-mediated
      hydrolysis/condensation of BaTiF6 generates nanocrystalline BaTiOF4 (a high
      temperature intermediate to BaTiO3) at 16 degrees C without any added acid or
      base, and the growth is templated along the protein filaments into floret
      microstructures. The unique combination of silicatein and the single-source
      molecular precursor has allowed a multimetallic perovskite-like material to be
      biocatalytically synthesized, in vitro, for the first time.

PMID- 16881661
TI  - Comparison of thermodynamic and kinetic aspects of oxidative addition of PhE-EPh
      (E = S, Se, Te) to Mo(CO)3(PR3)2, W(CO)3(PR3)2, and Mo(N[tBu]Ar)3 complexes. The
      role of oxidation state and ancillary ligands in metal complex induced
      chalcogenyl radical generation.
AB  - Enthalpies of oxidative addition of PhE-EPh (E = S, Se, Te) to the M(0) complexes
      M(PiPr3)2(CO)3 (M = Mo, W) to form stable complexes M(*EPh)(PiPr3)2(CO)3 are
      reported and compared to analogous data for addition to the Mo(III) complexes
      Mo(N[tBu]Ar)3 (Ar = 3,5-C6H3Me2) to form diamagnetic Mo(IV) phenyl chalcogenide
      complexes Mo(N[tBu]Ar)3(EPh). Reactions are increasingly exothermic based on
      metal complex, Mo(PiPr3)2(CO)3 < W(PiPr3)2(CO)3 < Mo(N[tBu]Ar)3, and in terms of
      chalcogenide, PhTe-TePh < PhSe-SePh < PhS-SPh. These data are used to calculate
      LnM-EPh bond strengths, which are used to estimate the energetics of production
      of a free *EPh radical when a dichalcogenide interacts with a specific metal
      complex. To test these data, reactions of Mo(N[tBu]Ar)3 and Mo(PiPr3)2(CO)3 with
      PhSe-SePh were studied by stopped-flow kinetics. First- and second-order
      dependence on metal ion concentration was determined for these two complexes,
      respectively, in keeping with predictions based on thermochemical data. ESR data
      are reported for the full set of bound chalcogenyl radical complexes
      (PhE*)M(PiPr3)2(CO)3; g values increase on going from S to Se, to Te, and from Mo
      to W. Calculations of electron densities of the SOMO show increasing electron
      density on the chalcogen atom on going from S to Se to Te. The crystal structure
      of W(*TePh)(PiPr3)2(CO)3 is reported.

PMID- 16881662
TI  - Ultrastable substrates for surface-enhanced Raman spectroscopy: Al2O3 overlayers
      fabricated by atomic layer deposition yield improved anthrax biomarker detection.
AB  - A new method to stabilize and functionalize surfaces for surface-enhanced Raman
      spectroscopy (SERS) is demonstrated. Atomic layer deposition (ALD) is used to
      deposit a sub-1-nm alumina layer on silver film-over-nanosphere (AgFON)
      substrates. The resulting overlayer maintains and stabilizes the SERS activity of
      the underlying silver while presenting the surface chemistry of the alumina
      overlayer, a commonly used polar adsorbent in chromatographic separations. The
      relative affinity of analytes for alumina-modified AgFON substrates can be
      determined by their polarity. On the basis of SERS measurements, dipicolinic acid
      displays the strongest binding to the ALD alumina-modified AgFON among a set of
      pyridine derivatives with varying polarity. This strong affinity for carboxylate
      groups makes the SERS substrate an ideal candidate for bacillus spores detection
      using the dipicolinate biomarker. The SERS signal from extracted dipicolinate was
      measured over the spore concentration range 10(-14)-10(-12) M to determine the
      saturation binding capacity of the alumina-modified AgFON surface. The adsorption
      constant was determined to be Kspore = 9.0 x 10(13) M(-1). A 10-s data collection
      time is capable of achieving a limit of detection of approximately 1.4 x 10(3)
      spores. The shelf life of prefabricated substrates is at least 9 months prior to
      use. In comparison to the bare AgFON substrates, the ALD-modified AgFON
      substrates demonstrate twice the sensitivity with 6 times shorter data
      acquisition time and 7 times longer temporal stability. ALD expands the palette
      of available chemical methods to functionalize SERS substrates, which will enable
      improved and diverse chemical control over the nature of analyte-surface binding
      for biomedical, homeland security, and environmental applications.

PMID- 16881663
TI  - Formation of nearly monodisperse In2O3 nanodots and oriented-attached
      nanoflowers: hydrolysis and alcoholysis vs pyrolysis.
AB  - Single crystalline and nearly monodisperse In2O3 nanocrystals with both dot and
      flower shapes were synthesized in a simple reaction system. This system used
      indium carboxylates as the precursors with or without alcohol as the activating
      reagents in a hydrocarbon solvent under elevated temperatures. Limited ligand
      protection (LLP) led to three-dimensional (3D) oriented attachment of nanodots,
      resulting in 3D nanoflowers. When the system had sufficient ligand protection for
      the nanocrystals, nanodots were found to be the stable products. The diameters of
      nearly monodisperse nanodots and nanoflowers were varied in a range from
      approximately 5 to approximately 15 nm and approximately 15 to approximately 60
      nm, respectively. The simple reaction system made it possible to have a
      systematic study of the reaction mechanisms along with the growth kinetics of
      nanocrystals. Hydrolysis and alcoholysis were identified as the major paths for
      this system, as opposed to pyrolysis. Both nearly monodispersed nanodots and
      nanoflowers can be made through either of the reaction pathways. Hydrolysis was
      found as a reversible pathway, and alcoholysis was confirmed to be irreversible.
      Consequently, a sufficient amount of alcohol was able to force the yield of
      nanocrystals, both dots and flowers, to unity.

PMID- 16881664
TI  - Spectroscopy and electrochemistry of cytochrome P450 BM3-surfactant film
      assemblies.
AB  - We report analyses of electrochemical and spectroscopic measurements on
      cytochrome P450 BM3 (BM3) in didodecyldimethylammonium bromide (DDAB) surfactant
      films. Electronic absorption spectra of BM3-DDAB films on silica slides reveal
      the characteristic low-spin FeIII heme absorption maximum at 418 nm. A prominent
      peak in the absorption spectrum of BM3 FeII-CO in a DDAB dispersion is at 448 nm;
      in spectra of aged samples, a shoulder at approximately 420 nm is present.
      Infrared absorption spectra of the BM3 FeII-CO complex in DDAB dispersions
      feature a time-dependent shift of the carbonyl stretching frequency from 1950 to
      2080 cm(-1). Voltammetry of BM3-DDAB films on graphite electrodes gave the
      following results: FeIII/II E(1/2) at -260 mV (vs SCE), approximately 300 mV
      positive of the value measured in solution; DeltaS degrees (rc), DeltaS degrees ,
      and DeltaH degrees values for water-ligated BM3 in DDAB are -98 J mol(-1) K(-1), 
      163 J mol(-1) K(-1), and -47 kJ mol(-1), respectively; values for the imidazole
      ligated enzyme are -8 J mol(-1) K(-1), -73 J mol(-1) K(-1), and -21 kJ mol(-1).
      Taken together, the data suggest that BM3 adopts a compact conformation within
      DDAB that in turn strengthens hydrogen bonding interactions with the heme axial
      cysteine, producing a P420-like species with decreased electron density around
      the metal center.

PMID- 16881665
TI  - Lithium diisopropylamide-mediated enolization: catalysis by hemilabile ligands.
AB  - Structural, kinetic, and computational studies reveal the mechanistic
      complexities of a lithium diisopropylamide (LDA)-mediated ester enolization.
      Hemilabile amino ether MeOCH2CH2NMe2, binding as an eta1 (ether-bound) ligand in
      the reactant and as an eta2 (chelating) ligand in the transition structure,
      accelerates the enolization 10,000-fold compared with n-BuOMe. At the onset of
      the reaction, a dimer-based enolization prevails. As the reaction proceeds,
      significantly less reactive LDA-enolate mixed dimers appear and divert the
      reaction through monomer- and mixed dimer-based pathways. The mechanistic and
      computational investigations lead to a proof-of-principle ligand-catalyzed
      enolization in which an ancillary ligand allows the catalytic ligand to re-enter
      the catalytic cycle.

PMID- 16881666
TI  - Size-dependent extinction coefficients of PbS quantum dots.
AB  - We report here on a detailed study on PbS colloidal quantum dots. A
      characterization via X-ray diffraction (XRD) and high-resolution transmission
      electron microscopy (HRTEM) allowed us to reliably determine the diameter and the
      shape of the nanocrystals. These data, together with second-derivative analysis
      of the absorption spectra, allowed us to determine the size dependence of seven
      transitions in the absorption spectrum; some of these transitions were identified
      on the basis of their normalized confinement energy. The size dependence of the
      first excitonic transition was best modeled by a four-band envelope approach
      which considers the anisotropy of the band edges (Andreev, A. D.; Lipovskii, A.
      A. Phys. Rev. B: Condens. Matter Mater. Phys. 1999, 59, 15402-15404). The
      extinction coefficients were calculated using concentrations obtained from
      inductively coupled plasma atomic emission spectrometry (ICP-AES), and their size
      dependence was found to follow a power law with exponent equal to approximately
      2.5. In contrast with what was expected from the effective mass approximation,
      the per particle absorption cross section of the lowest transition was found to
      be strongly dependent on the particle size.

PMID- 16881667
TI  - Glass transition and enthalpy relaxation of amorphous food saccharides: a review.
AB  - Many food materials exist in a disordered amorphous solid state due to
      processing. Therefore, understanding the concept of amorphous state, its
      important phase transition (i.e., glass transition), and the related phenomena
      (e.g., enthalpy relaxation) is important to food scientists. Food saccharides,
      including mono-, di-, oligo-, and polysaccharides, are among the most important
      major components in food. Focusing on the food saccharides, this review covers
      important topics related to amorphous solids, including the concept and molecular
      arrangement of amorphous solid, the formation of amorphous food saccharides, the
      concept of glass transition and enthalpy relaxation, physical property changes
      and molecular mobility around the glass transition, measurement of the glass
      transition and enthalpy relaxation, their mathematical descriptions and models,
      and influences on food stability.

PMID- 16881668
TI  - Development of a chemiluminescent ELISA for determining chloramphenicol in
      chicken muscle.
AB  - An indirect competitive enzyme-linked immunosorbent assay (ELISA) with
      chemiluminescent (CL) detection for chloramphenicol (CAP) in chicken muscle was
      developed. CAP-specific polyclonal antibody was raised in rabbit with a CAP
      succinate derivative conjugated with bovine serum albumin. Luminol solution was
      used as the substrate of horseradish peroxidase. The detection limit was 6 ng/L.
      The CL-ELISA was 10 times more sensitive compared to the colorimetric-ELISA. When
      CAP was spiked in chicken muscle at levels of 0.05-5 microg/kg, recoveries ranged
      from 97 to 118% with coefficients of variation of 6-22%. In an actual residue
      study, the results obtained by CL-ELISA correlated well with those obtained by
      gas chromatography with microcell electron capture detector. The residue levels
      of CAP in treated chicken decreased with time and dropped rapidly after the first
      6 h from around 50 to 10 microg/kg. After 3 days, CAP was not detected in chicken
      muscle. The developed method is therefore suitable for screening of CAP in
      chicken muscle samples.

PMID- 16881669
TI  - Development of a methodology for calcium, iron, potassium, magnesium, manganese,
      and zinc quantification in teas using X-ray spectroscopy and multivariate
      calibration.
AB  - In this study an analytical methodology for food analyses combining X-ray
      spectroscopy (XRS) with partial least-squares (PLS) data treatment was developed.
      Fifteen tea samples were purchased at a local market, and XRS spectra were
      obtained without sample pretreatment. For comparison of the metal concentrations,
      the samples were also mineralized, and six elements were determined using flame
      atomic absorption spectrometry (Ca, Fe, Mg, and Mn), flame atomic emission
      spectrometry (K), and thermospray flame furnace atomic absorption spectrometry
      (Zn). The spectral information obtained from XRS and the metal concentrations
      found using the alternative techniques were employed to generate six PLS models.
      The Ca and Mn models required four latent variables (LV), Fe, five LV, K, two LV,
      and Mg and Zn, three LV. The limits of quantification for these models were 614,
      134, 761, 140, 85, and 1 mg kg(-1) for Ca, Fe, K, Mg, Mn, and Zn, respectively.

PMID- 16881670
TI  - Determination and levels of the biocide ortho-phenylphenol in canned beers from
      different countries.
AB  - A method was developed for the determination of the biocide ortho-phenylphenol
      (biphenyl-2-ol; OPP) in beer, using deuterated OPP as an internal standard. A new
      liquid-liquid extraction procedure, employing acetonitrile, diethyl ether, and n
      pentane, afforded rapid phase separation. The evaporated extract was derivatized
      with pentafluorobenzyl bromide in a water-acetonitrile mixture that was buffered
      with potassium carbonate, followed by extraction of the derivative into
      cyclohexane and analysis by gas chromatography-mass spectrometry in electron
      ionization mode. The method enables the detection of OPP in 50 mL of beer at
      concentrations as low as 0.1 microg/L and provides a linear range of
      quantification of 0.5-40 microg/L. Samples from 61 beers canned over the past 12
      years and sold in 27 countries were analyzed for OPP. In 40 of them, the target
      compound was present at concentrations of 1.2-40 microg/L. Our investigations
      indicate that the ends of the cans, which contain sealing material presumably
      treated with OPP, are responsible for this contamination.

PMID- 16881671
TI  - Simple and sensitive determination of o-phenylphenol in citrus fruits using gas
      chromatography with atomic emission or mass spectrometric detection.
AB  - In this work, a simple and sensitive method for the analysis of the pesticide o
      phenylphenol (OPP) on citrus fruits was developed. OPP is extracted with
      dichloromethane by ultrasonication and derivatized with ferrocenecarboxylic acid
      chloride. Using ferrocene as a label, residues of OPP are determined by gas
      chromatography with atomic emission detection in the iron selective mode or with
      mass spectrometric detection. Sample cleanup is simple and rapid and merely
      involves a removal of excess reagent on an alumina minicolumn. The method
      detection limit is 2 ng of OPP/g of fruit, and recoveries from lemon samples
      fortified at levels of 35 and 140 ng/g are 101 and 106%, respectively. The citrus
      fruits analyzed (oranges, grapefruits, lemons) contained between 60 ng/g and 0.37
      microg/g OPP (RSD = 8-13%), and the results were in good agreement with results
      obtained when OPP was analyzed using an established HPLC-FLD method. Several
      alcohols could also be identified in the fruit peel.

PMID- 16881672
TI  - Isolation and characterization of cellulose obtained from ultrasonic irradiated
      sugarcane bagasse.
AB  - Cell walls of sugarcane bagasse were first delignified with chlorite followed by
      ultrasonic irradiation and then by two-step sequential extractions at 23 degrees
      C with 15 and 18% KOH for 2 h, 15 and 18% NaOH for 2 h, 8 and 10% KOH for 12 h,
      and 8 and 10% NaOH for 12 h and by a single one-stage isolation with 10% KOH for
      16 h and with 10% NaOH for 16 h, which released 79.4, 81.8, 83.6, 85.7, 61.5, and
      65.6% of the original hemicelluloses, and subsequently yielded 50.7, 49.5, 48.6,
      47.8, 57.2, and 55.4% of the cellulose, respectively. The six cellulosic
      preparations were free of bound lignin and had a purity of 77.1-90.1% with the
      intrinsic viscosity (eta), viscosity average degree of polymerization, and
      molecular weight (M(w)) ranging from 534.1 to 631.6 mL g(-1), from 1858.1 to
      2238.2 mL g(-1), and from 301000 to 362600 g mol(-1), respectively. The
      structural features of the isolated six cellulosic samples were comparatively
      examined by Fourier transform infrared and cross-polarization/magic angle
      spinning (13)C NMR spectroscopy and X-ray diffraction, and their thermal
      stability was investigated by using thermogravimetric analysis. It was found that
      all of the cellulosic preparations have the typical cellulose I structure but the
      crystallinity of the SCB cellulose was lower than that of flax, cotton, and
      kenaf.

PMID- 16881673
TI  - Rapid detection and identification of Pseudomonas aeruginosa and Escherichia coli
      as pure and mixed cultures in bottled drinking water using fourier transform
      infrared spectroscopy and multivariate analysis.
AB  - Fourier transform infrared (FT-IR) spectroscopy and multivariate analysis were
      used to identify Pseudomonas aeruginosa and Escherichia coli ATCC 25922
      inoculated into bottled drinking water. Three inoculation treatments were
      examined: (i) E. coli ATCC 25922 (N = 3), (ii) P. aeruginosa (N = 3), and (iii) a
      1:1 (v:v) mixed culture of both P. aeruginosa and E. coli ATCC 25922 (N = 3). The
      control treatment was noninoculated drinking water (N = 3). Second derivative
      transformation and loadings plots over the range of 1800-900 cm(-1) indicate
      variations in the following bacterial constituents: amide I band ca. 1650 cm(-1),
      amide II band ca. 1540 cm(-1), phosphodiester backbone of nucleic acids ca. 1242
      and 1080 cm(-1), and polysaccharide compounds ca. 1050-950 cm(-1). Cells with the
      different treatments were clearly segregated from a mean centered principal
      component analysis. By using soft independent modeling of class analogy analysis,
      spectra from a given treatment could be correctly classified 83-88% of the time.
      These results suggest that FT-IR spectroscopy can determine whether a pure
      culture is present, in addition to confirming that this method can discriminate
      between closely related bacteria based on differences in biochemical and
      phenotypic characteristics that can be detected in this spectral region.

PMID- 16881674
TI  - Development of a stable isotope dilution analysis with liquid chromatography
      tandem mass spectrometry detection for the quantitative analysis of di- and
      trihydroxybenzenes in foods and model systems.
AB  - A straightforward stable isotope dilution analysis (SIDA) for the quantitative
      determination of the di- and trihydroxybenzenes catechol (1), pyrogallol (2), 3
      methylcatechol (3), 4-methylcatechol (4), and 4-ethylcatechol (5) in foods by
      means of liquid chromatography-tandem mass spectrometry was developed. With or
      without sample preparation involving phenylboronyl solid phase extraction, the
      method allowed the quantification of the target compounds in complex matrices
      such as coffee beverages with quantification limits of 9 nmol/L for 4
      ethylcatechol, 24 nmol/L for catechol, 3-methyl-, and 4-methylcatechol, and 31
      nmol/L for pyrogallol. Recovery rates for the analytes ranged from 97 to 103%.
      Application of the developed SIDA to various commercial food samples showed that
      quantitative analysis of the target compounds is possible within 30 min and gave
      first quantitative data on the amounts of di- and trihydroxybenzenes in coffee
      beverage, coffee powder, coffee surrogate, beer, malt, roasted cocoa powder,
      bread crust, potato crisps, fruits, and cigarette smoke and human urine. Model
      precursor studies revealed the carbohydrate/amino acid systems as well as the
      plant polyphenols catechin and epicatechin as precursors of catechol and 5-O
      caffeoylquinic acid, caffeic acid as a precursor of catechol and 4-ethylcatechol,
      and gallocatechin, epigallocatechin, and gallic acid as precursors of pyrogallol.

PMID- 16881675
TI  - Structure-DPPH* scavenging activity relationships: parallel study of catechol and
      guaiacol acid derivatives.
AB  - The scavenging behavior of a series of catechol and guaiacol acid derivatives
      toward DPPH(*) was examined having as a starting point the order of activity
      derived on the basis of theoretically calculated BDE values. The studied
      compounds were protocatechuic, homoprotocatechuic, dihydrocaffeic, and caffeic
      acids and also vanillic, homovanillic, dihydroferulic, and ferulic acids.
      Catechol and guaiacol were used as reference compounds. Observations from the
      parallel study were made with regard to structural features (number and position
      of hydroxyl groups and the side-carbon chain characteristics) that regulated the
      behavior of the compounds experimentally. The exceptional DPPH(*) scavenging
      behavior observed for homoprotocatechuic acid in ethanol and for caffeic acid in
      acetonitrile could not be supported by the respective BDE values. Ferulic was the
      most active among guaiacolic acids, whereas dihydroferulic exhibited the highest
      stoichiometry. Ionizable carboxylic groups seem to affect considerably the
      relative order of activity as was also evidenced using the ORAC assay. Questions
      raised about the validity of widely accepted views on criteria for SARs are
      discussed with regard to literature findings.

PMID- 16881676
TI  - Chromoplast morphology and beta-carotene accumulation during postharvest ripening
      of Mango Cv. 'Tommy Atkins'.
AB  - Accumulation of beta-carotene and trans-cis isomerization of ripening mango
      mesocarp were investigated as to concomitant ultrastructural changes. Proceeding
      postharvest ripening was shown by relevant starch degradation, tissue softening,
      and a rising sugar/acid ratio, resulting in a linear decrease (R (2) = 0.89) of a
      ripening index (RPI(KS)) with increasing ripening time. A modest accumulation of
      all-trans-beta-carotene and its cis isomers resulted in a slight pigmentation of
      the mango chromoplasts, because ambient temperatures of 18.2-19.5 degrees C
      provided suboptimal ripening conditions, affecting color development and beta
      carotene biosynthesis. The ultrastructures of chromoplasts from mango mesocarp
      and carrot roots were comparatively studied by means of light and transmission
      electron microscopy. Irrespective of the ripening stage, mango chromoplasts
      showed numerous plastoglobuli varying in size and electron density. They
      comprised the main part of carotenoids, thus supporting the partial
      solubilization of the pigments in lipid droplets. However, because different
      pigment-carrying tubular membrane structures were also observed, mango
      chromoplasts were assigned to the globular and reticulotubular types, whereas the
      crystalline type was confirmed for carrot chromoplasts. The large portions of
      naturally occurring cis-beta-carotene in mango fruits contrasted with the
      predominance of the all-trans isomer characteristic of carrots, indicating that
      the nature of the structure where carotenoids are deposited and the physical
      state of the pigments are crucial for the stability of the all-trans
      configuration.

PMID- 16881677
TI  - Production of ascorbyl palmitate by surfactant-coated lipase in organic media.
AB  - The surface of a lipase from Burkholderia cepacia was coated with a nonionic
      surfactant, propylene glycol monostearate, and was used as a biocatalyst in the
      production of ascorbic acid in tert-butyl alcohol. The influence of various
      factors such as the type of surfactant, the pH of the buffer used for coating,
      the amount of surfactant in the coating, the organic solvent, and the temperature
      and molar ratio of the substrates used in the reaction on the conversion of
      ascorbyl palmitate were studied. After 24 h of reaction at 50 degrees C, a
      conversion of 47% was obtained using an ascorbic acid to palmitic acid molar
      ratio of 1:6. The native lipase showed only 6% conversion.

PMID- 16881679
TI  - Consumption of juice fortified with oregano extract markedly increases excretion
      of phenolic acids but lacks short- and long-term effects on lipid peroxidation in
      healthy nonsmoking men.
AB  - Oregano has been shown to possess antioxidant capacity in various in vitro models
      and has thus been suggested to be potentially beneficial to human health, but
      studies in humans are lacking. The aim of this study was to investigate the
      bioavailability and the effects of Origanum vulgare extract supplementation on
      serum lipids and lipid peroxidation in healthy nonsmoking men. A four-week double
      blinded supplementation trial was concluded in which volunteers (n = 45) were
      randomized to consume daily mango-orange juice (placebo), mango-orange juice
      enriched with 300 mg/d total phenolic compounds from oregano extract, or mango
      orange juice enriched with 600 mg/d total phenolic compounds from oregano
      extract. The excretion of phenolic compounds was markedly increased in the higher
      phenolic group as compared to the placebo group, but no significant changes were
      observed in the safety parameters, serum lipids, or biomarkers of lipid
      peroxidation.

PMID- 16881678
TI  - Rumex induratus leaves: interesting dietary source of potential bioactive
      compounds.
AB  - The phenolic compounds of Rumex induratus leaves were determined by HPLC-DAD
      MS/MS-ESI. The results revealed a profile composed of 19 compounds: caffeoyl
      hexoside, two p-coumaroyl-hexoside isomers, feruloyl-hexoside, sinapoyl-hexoside,
      6-C-hexosyl-quercetin, 8-C-hexosyl-luteolin, 6-C-hexosyl-luteolin, 6-C-hexosyl
      apigenin, 3-O-hexosyl-quercetin, 3-O-rutinosyl-quercetin, 7-O-hexosyl-diosmetin,
      3-O-rutinosyl-isorhamnetin, 7-O-(acetyl)-pento-hexosyl-diosmetin, 6-C-hexosyl
      genkwanin, and four unidentified O-glycosyl-C-glycosylflavones. The
      quantification of the identified phenolics by HPLC-DAD showed 6-C-hexosyl
      luteolin as the main compound. Organic acid composition was determined by HPLC
      UV, revealing a high content of oxalic acid. R. induratus was also investigated
      for its capacity to act as a scavenger of DPPH and superoxide radicals. Good
      antioxidative results were obtained against both radicals. Unlike other species
      of the genus Rumex, R. induratus did not present any anthraquinone derivative.

PMID- 16881680
TI  - Isoflavone profiles of red clovers and their distribution in different parts
      harvested at different growing stages.
AB  - The isoflavone compositions and concentrations in the leaf, flower, petiole, and
      stem of 13 red clover cultivars were studied using high-performance liquid
      chromatography coupled with a diode array and a mass spectrometric detector with
      negative electrospray ionization. Different cultivars showed significantly
      different concentrations of individual and total isoflavones. The leaf contained
      the highest overall concentration, followed by the stem, petiole, and flower.
      Biochanin A and formononetin were the predominant isoflavones in all cultivars
      and all parts, along with eight other minor aglycones, daidzein, genistein,
      glycitein, irilone, orobol, pratensein, pseudobaptigenin, and prunetin, and four
      minor malonylglycosides, genistein-7-glucoside-6' '-malonate, orobol-7-glucoside
      6' '-malonate, formononetin-7-glucoside-6' '-malonate, and biochanin A-7
      glucoside-6' '-malonate. The isoflavone compositions and concentrations were also
      found to be different between red clover parts harvested at the early bud stage
      and the late flowering stage. Sample storage and handling prior to analysis were
      also found to be important. Samples in this study were kept at -5 degrees C for a
      few days before being freeze-dried and were found to contain mainly the aglycones
      of isoflavones. This may actually be an advantage in that "natural" and more
      bioactive isoflavones can be obtained without using chemical hydrolysis. Findings
      in this study therefore provide important information for developing isoflavone
      rich red clovers and for optimizing harvest timing and choosing the right part of
      the red clover plant.

PMID- 16881681
TI  - Organosolv ethanol lignin from hybrid poplar as a radical scavenger: relationship
      between lignin structure, extraction conditions, and antioxidant activity.
AB  - Twenty-one organosolv ethanol lignin samples were prepared from hybrid poplar
      (Populus nigra xP. maximowiczii) under varied conditions with an experimental
      matrix designed using response surface methodology (RSM). The lignin preparations
      were evaluated as potential antioxidants. Results indicated that the lignins with
      more phenolic hydroxyl groups, less aliphatic hydroxyl groups, low molecular
      weight, and narrow polydispersity showed high antioxidant activity. Processing
      conditions affected the functional groups and molecular weight of the extracted
      organosolv ethanol lignins, and consequently influenced the antioxidant activity
      of the lignins. In general, the lignins prepared at elevated temperature, longer
      reaction time, increased catalyst, and diluted ethanol showed high antioxidant
      activity. Regression models were developed to enable the quantitative prediction
      of lignin characteristics and antioxidant activity based on the processing
      conditions.

PMID- 16881682
TI  - Preparation and characterization of chitosan-based nanocomposite films with
      antimicrobial activity.
AB  - Four different types of chitosan-based nanocomposite films were prepared using a
      solvent-casting method by incorporation with four types of nanoparticles, that
      is, an unmodified montmorillonite (Na-MMT), an organically modified
      montmorillonite (Cloisite 30B), a Nano-silver, and a Ag-zeolite (Ag-Ion). X-ray
      diffraction patterns of the nanocomposite films indicated that a certain degree
      of intercalation was formed in the nanocomposite films, with the highest
      intercalation in the Na-MMT-incorporated films followed by films with Cloisite
      30B and Ag-Ion. Scanning electron micrographs showed that in all of the
      nanocomposite films, except the Nano-silver-incorporated one, nanoparticles were
      dispersed homogeneously throughout the chitosan polymer matrix. Consequently,
      mechanical and barrier properties of chitosan films were affected through
      intercalation of nanoparticles, that is, tensile strength increased by 7-16%,
      whereas water vapor permeability decreased by 25-30% depending on the
      nanoparticle material tested. In addition, chitosan-based nanocomposite films,
      especially silver-containing ones, showed a promising range of antimicrobial
      activity.

PMID- 16881683
TI  - Directed evolution and characterization of a novel D-pantonohydrolase from
      Fusarium moniliforme.
AB  - D-Pantonohydrolase has attracted increasing attention as a biocatalyst for
      stereospecific production of D-pantoic acid. The Fusarium moniliforme D
      pantonohydrolase was selected for directed evolution through error-prone
      Polymerase Chain Reaction (PCR) combined with DNA shuffling for improved activity
      and pH stability using a convenient two-step high-throughput screening method
      based on the product formation and pH indicator. After three sequential error
      prone PCRs and two rounds of DNA shuffling followed by screening, about 60
      positive mutants were produced and a best mutant, Mut H-1287, with improved
      activity and pH stability was obtained. As compared to wild-type D
      pantonohydrolase, Mut H-1287 showed a 10.5-fold higher specific activity;
      moreover, it could retain 85% of its original activity after incubation under low
      pH. Gene analysis indicated that the Mut H-1287 had D63H, K118Q, and V241I
      substitutions. The wild-type and evolved D-pantonohydrolase (Mut H-1287) was
      purified in three steps. The activities and characteristics of purified wild-type
      and evolved D-pantonohydrolase were also studied and compared.

PMID- 16881684
TI  - Efficient production of active recombinant Candida rugosa LIP3 lipase in Pichia
      pastoris and biochemical characterization of the purified enzyme.
AB  - Candida rugosa lipase (CRL), an important industrial enzyme, possesses several
      different isoforms encoded by the high-identity lip gene family (lip1 to lip7).
      In this study, an additional N-terminal peptide in front of the lip3 gene was
      removed by PCR, and the 18 nonuniversal serine codons (CTG) of the lip3 gene were
      converted into universal serine codons (TCT) by means of an overlap extension PCR
      based multiple-site-directed mutagenesis to express an active recombinant LIP3 in
      the yeast Pichia pastoris. The regional synthetic DNA fragment (339 bp) is first
      recombined by primer assembly with 20 overlapping nucleotides, followed by
      specific overlap extension PCR with outside primers containing restriction enzyme
      sites for directional cloning into the pGAPZalphaC vector. The results show that
      the production yield (0.687 unit/mL) of N-fused lip3 (nflip3) has an overall
      improvement of 69-fold relative to that (0.01 unit/mL) of lip3 and of 52-fold
      (0.47 unit/mL) of codon-optimized lip3 (colip3) relative to that (0.01 unit/mL)
      of non-codon-optimized lip3 (lip3), with the cultivation time set at 5 days. This
      finding demonstrates that the reservation of the N terminus and the regional
      codon optimization of the lip3 gene fragment at the 5' end can greatly increase
      the expression level of recombinant LIP3 in the P. pastoris system. The purified
      recombinant LIP3 shows distinct biochemical properties compared with other
      isoforms.

PMID- 16881685
TI  - Sulfur and adenine metabolisms are linked, and both modulate sulfite resistance
      in wine yeast.
AB  - Sulfite treatment is the most common way to prevent grape must spoilage in
      winemaking because the yeast Saccharomyces cerevisiae is particularly resistant
      to this chemical. In this paper we report that sulfite resistance depends on
      sulfur and adenine metabolism. The amount of adenine and methionine in a
      chemically defined growth medium modulates sulfite resistance of wine yeasts.
      Mutations in the adenine biosynthetic pathway or the presence of adenine in a
      synthetic minimal culture medium increase sulfite resistance. The presence of
      methionine has the opposite effect, inducing a higher sensitivity to SO(2). The
      concentration of methionine, adenine, and sulfite in a synthetic grape must
      influences the progress of fermentation and at the transcriptional level the
      expression of genes involved in sulfur (MET16), adenine (ADE4), and acetaldehyde
      (ALD6) metabolism. Sulfite alters the pattern of expression of all these genes.
      This fact indicates that the response to this stress is complex and involves
      several metabolic pathways.

PMID- 16881686
TI  - Glycoalkaloid development during greening of fresh market potatoes (Solanum
      tuberosum L.).
AB  - Chlorophyll and glycoalkaloid synthesis in potato (Solanum tuberosum L.) tubers
      occur in direct response to light. The two processes are concurrent, but
      independent. Color photographic indices to subjectively grade fresh market
      potatoes for the extent of greening were developed under lighting conditions
      consistent with those of retail markets. Total glycoalkaloid (TGA) and
      chlorophyll accumulation for four cultivars were determined over the respective
      greening scales, thus calibrating the scales for TGA content. On average, TGA
      concentrations in complete longitudinal sections of tubers (flesh samples) were
      highest in Dark Red Norland followed by Russet Norkotah, Yukon Gold, and White
      Rose. TGA concentrations of flesh samples of White Rose and Yukon Gold tubers
      were somewhat variable and did not increase in direct proportion to greening
      level and chlorophyll content, particularly at higher levels of greening. TGA
      concentrations in Dark Red Norland and Russet Norkotah tubers were highly
      correlated (P < or = 0.001) with greening level and chlorophyll concentrations.
      When averaged over greening levels, skin samples contained 3.4- to 6.8-fold
      higher concentrations of TGAs than flesh samples, depending on the cultivar. The
      TGA concentration in periderm samples ranged from 37 to 160 mg/100 g of dry wt.
      Regardless of greening level, concentrations of TGAs in the flesh samples
      (including attached periderm) remained within limits presumed safe for human
      consumption. Discrimination of greened tubers on the basis of perceived
      glycoalkaloid toxicity is likely unfounded for the cultivars and greening levels
      studied.

PMID- 16881687
TI  - Lipolysis during ripening of Emmental cheese considering organization of fat and
      preferential localization of bacteria.
AB  - This study followed the progression of lipolysis in Emmental cheese by
      quantifying the concentrations of individual free fatty acids (FFA) released
      during ripening in each of the different rooms: 12 days at 12 degrees C, 28 days
      at 21 degrees C, and 8 days at 4 degrees C. Lipolysis, which corresponded to
      1.56% of fat, mainly occurred in the 21 and 4 degrees C rooms, with 68 and 16.5%
      of total FFA, respectively. The nonselectivity of lipolytic enzymes was
      evidenced: all fatty acids were released with level of > or =1%. Differential
      scanning calorimetry experiments showed that the thermal properties of cheese
      were affected by (i) lipolysis of fat, that is, the monoacylglycerols,
      diacylglycerols, and FFA that may be localized at the fat/whey interface, and/or
      by (ii) hydrolysis of high-melting-point triacylglycerols constituted mainly by
      long-chain saturated fatty acids (e.g., palmitic acid). Analysis of the cheese
      microstructure was performed using confocal laser scanning microscopy. Fat
      globules were mainly disrupted after pressing of curd grains, leading to the
      release of the milk fat globule membrane (MFGM); fat inclusions were surrounded
      by pockets of whey, delimited by casein strands. Moreover, colonies of bacteria
      were preferentially localized in situ at the fat/protein interface. This study
      showed that both the localization of bacteria and the supramolecular organization
      of fat which was not protected by the MFGM can help the accessibility of milk fat
      to lipolytic enzymes and then contribute to the quality of cheese.

PMID- 16881688
TI  - Carotenoid changes of intact watermelons after storage.
AB  - Watermelon contains lycopene, a red carotenoid pigment that has strong
      antioxidant properties. The lycopene content of watermelon is substantial,
      contributing 8-20 mg per 180 g serving. There are no reports on carotenoid
      changes in whole watermelon during storage. Three types of watermelon, open
      pollinated seeded, hybrid seeded, and seedless types, were stored at 5, 13, and
      21 degrees C for 14 days and flesh color, composition, and carotenoid content
      were compared to those of fruit not stored. Watermelons stored at 21 degrees C
      had increased pH, chroma, and carotenoid content compared to fresh fruit.
      Compared to fresh fruit, watermelons stored at 21 degrees C gained 11-40% in
      lycopene and 50-139% in beta-carotene, whereas fruit held at 13 degrees C changed
      little in carotenoid content. These results indicate that carotenoid biosynthesis
      in watermelons can be affected by temperature and storage.

PMID- 16881689
TI  - Involvement of negative feedback regulation in wound-induced ethylene synthesis
      in 'Saijo' persimmon.
AB  - Wounding is one of the most effective stress signals to induce ethylene synthesis
      in persimmon (Diospyros kaki Thunb.). We found that wound-induced ethylene
      biosynthesis is subjected to negative feedback regulation in mature 'Saijo'
      persimmon fruit since ethylene production was enhanced by 1-methylcyclopropene (1
      MCP) (an inhibitor of ethylene perception) pretreatment, which was approximately
      1.8 fold of that in control tissues (without 1-MCP pretreatment). Wound-induced 1
      aminocyclopropane-1-carboxylate (ACC) synthase activity and DK-ACS2 gene
      expression were substantially increased by 1-MCP pretreatment after 12 h, which
      resulted in much higher ACC content in 1-MCP pretreated tissues than that in a
      control after 24 h. These results indicated that wound-induced DK-ACS2 gene
      expression was negatively regulated by ethylene in mature persimmon fruit.
      However, 1-MCP pretreatment had no effect on DK-ACO1 gene expression, suggesting
      the independence of wound-induced DK-ACO1 on ethylene. Out of accord with DK-ACO1
      gene expression, ACC oxidase activity was enhanced 48 h after wounding in 1-MCP
      pretreated tissues, reaching a peak 1.5-fold higher than that in control tissues
      at 60 h.

PMID- 16881690
TI  - Molecular degradation rate of rice and corn starches during acid-methanol
      treatment and its relation to the molecular structure of starch.
AB  - The degradation rates of rice and corn starches with different contents of
      amylose treated in methanol containing 0.36% HCl at 25 degrees C for 1-15 days
      were evaluated by monitoring the weight average degree of polymerization of
      starch. A two-stage degradation pattern during acid-methanol treatment was found
      for the starches studied, which were the slow (first) and the rapid (second)
      degradation stages. Waxy starches showed a shorter time period of the first stage
      than that of nonwaxy starch. Rice starch showed a shorter time period of the
      first stage and a higher degradation rate of the second stage than the
      counterpart corn starch with similar amylose content. Despite the botanic source
      and amylose content of starch, the degradation rate of starch in the second stage
      significantly (p < 0.05) correlated to the S/L ratio (r = -0.886) and
      polydispersity (r = 0.859) of amylopectin branch chains of native starch.

PMID- 16881691
TI  - Phytate degradation in a mixture of ground wheat and ground defatted soybeans
      during feed processing: effects of temperature, moisture level, and retention
      time in small- and medium-scale incubation systems.
AB  - The optimal conditions for degradation of phytate (IP6, myo-inositol
      hexaphosphate) in a mixture of ground wheat and ground defatted soybeans (1:2,
      w/w) with added exogenous E. coli phytase were investigated at different
      temperatures (45, 60, 75, and 95 degrees C), moisture levels (25%, 35%, and 45%),
      and retention times (2-45 min). All treatment combinations were investigated in a
      small-scale mixer conditioner (experiment 1). The combined 45 degrees C and 45%
      moisture treatment was most efficient and reduced the content of IP6 by 86%
      during 45 min of incubation. This treatment combination was applied in a medium
      scale mixer conditioner (experiment 2), and 76% reduction of IP6 at 45 min was
      obtained. During incubation, the content of lower groups of inositol phosphates,
      such as IP4 (myo-inositol tetraphosphate) and IP3 (myo-inositol triphosphate),
      increased significantly as the content of IP6 decreased. The major isomer formed
      was Ins(1,2,5,6)P(4).

PMID- 16881692
TI  - Sonication-assisted extraction of chitin from North Atlantic shrimps (Pandalus
      borealis).
AB  - The influence of sonication during extraction of chitin from North Atlantic
      shrimp (NAS) shells (Pandalus borealis) on chitin yield, purity, and
      crystallinity was investigated. Shells were peeled, washed, lyophilized, ground,
      and suspended for 4 h in 0.25 M HCl (1:40) at 40 degrees C followed by
      ultrasonication at 41 W/cm(2) for 0, 1, and 4 h, respectively. Demineralized
      shells were lyophilized, resuspended in 0.25 M NaOH (1:40), and ultrasonicated at
      41 W/cm(2) for 0, 1, and 4 h to remove proteins. The yield and mineral and
      protein contents were determined after each processing step. The purity of
      extracted chitin was determined from the total amount of glucosamine. The
      crystallinity index and size of crystals were calculated from wide-angle X-ray
      scattering measurements. Scanning electron microscope images were recorded to
      evaluate morphological changes in samples. The yield of chitin from NAS decreased
      from 16.5 to 11.4% for 0 and 1 h sonicated samples, respectively, which was
      attributed to increased concentrations of depolymerized materials in the wash
      water. Sonication did not enhance the removal of minerals. The application of
      ultrasound enhanced the removal of proteins from 39.8 to 10.6, 8.3, and 7.3%
      after 0, 1, and 4 h of sonication treatments. The crystallinity index of chitin
      decreased from 87.6 to 79.1 and 78.5% after 1 and 4 h of sonication, yielding
      chitosans with crystallinity indices of 76.7, 79.5, and 74.8% after
      deacetylation, respectively. Fourier transform infrared spectroscopy scans
      indicated that the degree of acetylation of chitins was unaffected by sonication.
      Comparison of the extraction results of NAS with that from freshwater prawns
      indicated that more impurities were left in NAS chitin, suggesting that
      composition and structural arrangement of chitin in shells influence the
      efficiency of ultrasound-assisted extraction.

PMID- 16881693
TI  - Disruption and reassociation of casein micelles under high pressure: influence of
      milk serum composition and casein micelle concentration.
AB  - In this study, factors influencing the disruption and aggregation of casein
      micelles during high-pressure (HP) treatment at 250 MPa for 40 min were studied
      in situ in serum protein-free casein micelle suspensions. In control milk, light
      transmission increased with treatment time for approximately 15 min, after which
      a progressive partial reversal of the HP-induced increase in light transmission
      occurred, indicating initial HP-induced disruption of casein micelles, followed
      by reformation of casein aggregates from micellar fragments. The extent of HP
      induced micellar disruption was negatively correlated with the concentration of
      casein micelles, milk pH, and levels of added ethanol, calcium chloride, or
      sodium chloride and positively correlated with the level of added sodium
      phosphate. The reformation of casein aggregates during prolonged HP treatment did
      not occur when HP-induced disruption of casein micelles was limited (<60%) or
      very extensive (>95%) and was promoted by a low initial milk pH or added sodium
      phosphate, sodium chloride, or ethanol. On the basis of these findings, a
      mechanism for HP-induced disruption of casein micelles and subsequent aggregation
      of micellar fragments is proposed, in which the main element appears to be HP
      induced solubilization of micellar calcium phosphate.

PMID- 16881694
TI  - Influence of thermal processing conditions on acrylamide generation and browning
      in a potato model system.
AB  - Fried potato products such as French fries and chips may contain substantial
      amounts of acrylamide. Numerous efforts are undertaken to minimize the acrylamide
      content of these products while sensory properties such as color and flavor have
      to be respected as well. An optimization of the frying process can be achieved if
      the basic kinetic data of the browning and acrylamide formation are known.
      Therefore, heating experiments with potato powder were performed under controlled
      conditions (moisture, temperature, and time). Browning and acrylamide content
      both increased with heating time at all temperatures and moisture contents
      tested. The moisture content had a strong influence on the activation energy of
      browning and acrylamide formation. The activation energy strongly increased at
      moisture contents below 20%. At higher moisture contents, it was very similar for
      both parameters. At low moisture contents, the activation energy of acrylamide
      formation was larger as compared to the one for browning. This explains why the
      end of the frying process is very critical. Therefore, a lower temperature toward
      the end of frying reduces the acrylamide content of the product while color
      development is still good.

PMID- 16881696
TI  - Kinetic study of the thermal stability of tea catechins in aqueous systems using
      a microwave reactor.
AB  - Tea catechins may undergo complex reactions such as oxidation, polymerization,
      and epimerization during thermal processing. The thermal stability of tea
      catechins in an aqueous system, including degradation and epimerization
      reactions, was investigated using a microwave reactor. Reactions were controlled
      at high temperatures ranging from 100 to 165 degrees C with various durations up
      to 120 min. Three sources of tea catechins containing different levels of (-)
      epigallocatechin gallate (EGCG), (-)-epicatechin gallate (ECG), and their epimers
      were studied. Kinetic models for the degradation/epimerization of tea catechins
      were developed and validated by the reactions at 145 degrees C. It was shown that
      the epimerization and degradation of tea catechins followed first-order reactions
      and the rate constants of reaction kinetics followed the Arrhenius equation.
      Values of the activation energy (E(a)) for the epimerization of EGCG from epi- to
      nonepi-structures, the epimerization of GCG from nonepi- to epi-structures, and
      the total degradation of EGCG and its epimer GCG were 117.6, 84.2, and 42.8
      kJ/mol, respectively. For ECG and CG, the E(a) values were 119.3, 96.2, and 41.6
      kJ/mol, respectively. The mathematical models may provide a useful prediction for
      the loss of tea catechins during any thermal processing.

PMID- 16881695
TI  - Effect of postharvest storage on the expression of the apple allergen Mal d 1.
AB  - Consumption of fresh apples can cause allergy in susceptible individuals. A
      competitive enzyme-linked immunosorbent assay (ELISA) has been developed to
      determine Mal d 1 levels in apple pulp using a monoclonal antibody (BIP-1). The
      ELISA was able to rank ten cultivars according to their Mal d 1 content (between
      3.8 and 72.5 mug/g pulp). For the first time, it has been demonstrated that
      growing conditions and postharvest storage, using three different treatments over
      a 5 month period in 2 consecutive years, increase Mal d 1 expression at a
      translational and transcriptional level (3.5- and 8.5-fold under controlled
      atmosphere storage). Expression of three major Mal d 1 isoforms was observed by
      real-time polymerase chain reaction over the 5 month storage period, and Mal d
      1.02 was the most highly expressed isoform. In conclusion, Mal d 1 gene
      expression was significantly increased during modified atmosphere storage.
      Individuals suffering from birch pollen-apple allergy syndrome might experience
      fewer problems consuming freshly picked apples.

PMID- 16881697
TI  - Thermally generated 3-aminopropionamide as a transient intermediate in the
      formation of acrylamide.
AB  - On the basis of the recent findings that "biogenic amines" can also be formed
      during thermal food processing from their parent amino acids in a Strecker-type
      reaction, the formation of 3-aminopropionamide, the biogenic amine of asparagine,
      was investigated in model systems as well as in thermally processed Gouda cheese.
      The results of model studies revealed that, besides acrylamide, 3
      aminopropionamide was also formed in amounts of 0.1-0.4 mol % when asparagine was
      reacted in the presence of either glucose or 2-oxopropionic acid. Results of a
      second series of model experiments in which [(13)C(4)(15)N(2)]-asparagine
      ([(13)C(4)(15)N(2)]-Asn) and unlabeled 3-aminopropionamide were reacted together
      in the presence of glucose revealed a >12-fold higher efficacy of 3
      aminopropionamide in acrylamide generation as compared to asparagine. Both
      [(13)C(3)(15)N(2)]-3-aminopropionamide and [(13)C(3)(15)N(1)]-acrylamide were
      formed during [(13)C(4)(15)N(2)]-Asn degradation in a ratio of about 1:4,
      supporting the idea that 3-aminopropionamide is a transient intermediate in
      acrylamide formation. In this study, 3-aminopropionamide was identified and
      quantified for the first time in foods, namely, in Gouda cheese. Although the
      fresh cheese contained low amounts of 3-aminopropionamide, its concentrations
      were much increased to approximately 1300 mug/kg after thermal processing. In
      isotope labeling studies, performed by administering to the cheese
      [(13)C(4)(15)N(2)]-Asn in a ratio of 1:2 as compared to the "natural"
      concentrations of asparagine, similar ratios of unlabeled/labeled 3
      aminopropionamide and unlabeled/labeled acrylamide were determined. Thus, 3
      aminopropionamide could be verified as a transient intermediate of acrylamide
      formation during food processing.

PMID- 16881698
TI  - Toward a better understanding of the lignin isolation process from wood.
AB  - The recently developed protocol for isolating enzymatic mild acidolysis lignins
      (EMAL) coupled with the novel combination of derivatization followed by reductive
      cleavage (DFRC) and quantitative (31)P NMR spectroscopy were used to better
      understand the lignin isolation process from wood. The EMAL protocol is shown to
      offer access at lignin samples that are more representative of the overall lignin
      present in milled wood. The combination of DFRC/(31)P NMR provided a detailed
      picture on the effects of the isolation conditions on the lignin structure. More
      specifically, we have used vibratory and ball milling as the two methods of wood
      pulverization and have compared their effects on the lignin structures and
      molecular weights. Vibratory-milling conditions cause substantial lignin
      depolymerization. Lignin depolymerization occurs via the cleavage of uncondensed
      beta-aryl ether linkages, while condensed beta-aryl ethers and dibenzodioxocins
      were found to be resistant to such mechanical action. Condensation and side chain
      oxidations were induced mechanochemically under vibratory-milling conditions as
      evidenced by the increased amounts of condensed phenolic hydroxyl and carboxylic
      acid groups. Alternatively, the mild mechanical treatment offered by ball milling
      was found not to affect the isolated lignin macromolecular structure. However,
      the overall lignin yields were found to be compromised when the mechanical action
      was less intense, necessitating longer milling times under ball-milling
      conditions. As compared to other lignin preparations isolated from the same batch
      of milled wood, the yield of EMAL was about four times greater than the
      corresponding milled wood lignin (MWL) and about two times greater as compared to
      cellulolytic enzyme lignin (CEL). Molecular weight distribution analyses also
      pointed out that the EMAL protocol allows the isolation of lignin fractions that
      are not accessed by any other lignin isolation procedures.

PMID- 16881699
TI  - Purification and structure determination of glucosides of capsaicin and
      dihydrocapsaicin from various Capsicum fruits.
AB  - Two new glucosides, capsaicin-beta-D-glucopyranoside (1) and dihydrocapsaicin
      beta-D-glucopyranoside (2), were discovered in the fruit of the Capsicum annuum
      cultivar 'High Heat'. They were sequentially purified by acetone extraction, n
      hexane extraction, and acetonitrile extraction, followed by medium-pressure
      liquid chromatography and high-performance liquid chromatography performed on an
      octadecylsilane column. Their chemical structures were elucidated by proton
      nuclear magnetic resonance, carbon nuclear magnetic resonance, and hydrolysis
      with alpha- and beta-glucosidases. The glucosides were also detected in various
      pungent cultivars of C. annuum, Capsicum frutescens, and Capsicum chinense by
      liquid chromatography-mass spectrometry. However, they were not detected in
      nonpungent cultivars of C. annuum. Furthermore, a positive correlation was
      observed between the quantity of the capsaicinoids, capsaicin, and
      dihydrocapsaicin and their glucosides.

PMID- 16881700
TI  - N-(2-bromophenyl)-2-(4,6-dimethoxypyrimidin-2-yloxy)benzylamine, a new selective
      postemergent herbicide for weed control in winter oilseed rape.
AB  - N-(2-Bromophenyl)-2-(4,6-dimethoxypyrimidin-2-yloxy)benzylamine is a highly
      active herbicide, which belongs to a novel class of chemistry. The compound is de
      novo synthesized in good yield, and the structure is confirmed by (1)H NMR, IR,
      MS, microanalysis, and X-ray. Its herbicidal activity is assessed under
      greenhouse conditions. It is effective against many grass weed species, as well
      as broadleaf weeds, under greenhouse conditions. Field trials indicate that it
      controls major weeds with a good tolerance on oilseed rape by postemergence
      application at rates of 15-90 g of active ingredient/ha. This compound possesses
      low mammalian toxicity and favorable environmental profile. These results suggest
      that the compound has potential as a new selective postemergent herbicide in
      winter oilseed rape.

PMID- 16881701
TI  - Photodegradation of penoxsulam.
AB  - This study was carried out to characterize the photodegradation of penoxsulam and
      to evaluate the significance of photolysis for its fate and dissipation.
      Degradation studies of (14)C-labeled isotopes of penoxsulam in a "merry-go-round"
      reactor suggest that aqueous photodegradation proceeds via three possible
      pathways: cleavage of the sulfonamide bridge, stepwise degradation of the
      triazolopyrimidine system and its substituents, and photooxidation of the
      sulfonyl group. Seven major photoproducts were found, and six were identified.
      Two of the identified photodegradation products seem to be either rapidly
      biodegraded when formed or not formed in significant amounts in environmental
      conditions.

PMID- 16881702
TI  - Microbial degradation of penoxsulam in flooded rice field soils.
AB  - The degradation of penoxsulam [2-(2,2-difluoroethoxy)-N-5,8
      dimethoxy[1,2,4]triazolo[1,5-C]pyrimidin-2-yl-6-(trifluoromethyl)benzene
      sulfonamide] was studied in flasks simulating flooded rice field conditions using
      four representative rice field soils from the Sacramento Valley. Degradation half
      lives (t(1/2) values) ranged between 2 and 13 days. Increased degradation rates
      were observed in flask systems with steeper redox gradients between the flooded
      soil layer and the overlaying water. Two transient metabolites were identified
      that were temporarily formed in amounts exceeding 5% of the total initial mass of
      penoxsulam. The results of high-performance liquid chromatography/(14)C
      radiodetection studies indicate that the degradation of the triazolopyrimidine
      system and its substituents is the main pathway of microbial transformation
      processes. Microbial activity, as measured by dehydrogenase activity, was not
      affected by penoxsulam concentrations corresponding to the proposed maximum
      annual use rate of 40 g active ingredient/ha.

PMID- 16881704
TI  - Effect of citric acid and glycine addition on acrylamide and flavor in a potato
      model system.
AB  - Acrylamide levels in cooked/processed food can be reduced by treatment with
      citric acid or glycine. In a potato model system cooked at 180 degrees C for 10
      60 min, these treatments affected the volatile profiles. Strecker aldehydes and
      alkylpyrazines, key flavor compounds of cooked potato, were monitored. Citric
      acid limited the generation of volatiles, particularly the alkylpyrazines.
      Glycine increased the total volatile yield by promoting the formation of certain
      alkylpyrazines, namely, 2,3-dimethylpyrazine, trimethylpyrazine, 2-ethyl-3,5
      dimethylpyrazine, tetramethylpyrazine, and 2,5-diethyl-3-methylpyrazine. However,
      the formation of other pyrazines and Strecker aldehydes was suppressed. It was
      proposed that the opposing effects of these treatments on total volatile yield
      may be used to best advantage by employing a combined treatment at lower
      concentrations, especially as both treatments were found to have an additive
      effect in reducing acrylamide. This would minimize the impact on flavor but still
      achieve the desired reduction in acrylamide levels.

PMID- 16881703
TI  - Layered double hydroxides as supports for the slow release of acid herbicides.
AB  - A Mg/Al layered double hydroxide (LDH) was intercalated with the anionic
      herbicides 2,4-D, MCPA, and picloram by using three different methodologies: (i)
      direct synthesis (DS), (ii) regeneration (RE), and (iii) ion exchange (IE). The
      resulting complexes were characterized and assayed by batch release and column
      leaching tests, aiming at the controlled release of these herbicides. All the
      tested LDH-herbicide complexes displayed similar slow herbicide release
      properties in water, although the IE method seemed to result in complexes with a
      greater fraction of herbicide in a readily available form. Apparently, the LDH
      herbicide complexes released most of the active ingredient present in the
      complexes at the end of the batch release experiment. This was attributed to the
      replacement of the intercalated herbicide by carbonate and hydroxyl anions from
      the aqueous solution. Compared to the free herbicides, the application of the
      three LDH-herbicide complexes (RE) to soil columns resulted in reduction in the
      maximum herbicide concentration in leachates and led to the retardation of
      herbicide leaching through the soil. All LDH-herbicide complexes presented an
      herbicidal efficacy similar to that of the free (technical) herbicides. Our
      results indicated the potential applicability of LDHs as supports for the
      preparation of slow release formulations of acid herbicides such as 2,4-D, MCPA,
      or picloram.

PMID- 16881705
TI  - Odor thresholds of microbially induced off-flavor compounds in apple juice.
AB  - Microbially derived off-flavor is a major problem in apple juice production as it
      diminishes the sensory quality of the juice significantly. Fifteen relevant off
      flavor compounds that are formed in apple juice, for example, by the strains
      Alicyclobacillus acidoterrestris and Actinomycetes (Streptomyces ssp.) were
      investigated with respect to their sensory relevance. The odor threshold values
      (i.e., detection and recognition values) were determined for all compounds in the
      matrix apple juice. Odor threshold values for fenchyl alcohol are reported here
      for the first time. The obtained values were set in relation to the limits of
      detection and quantification of a previously published GC-MS method. Eight
      tainted apple juice samples were analyzed for the presence of the 2 strains and
      the 15 off-flavor compounds. Both strains could be found in the samples; the
      presence of Streptomyces ssp. as spoilage bacteria of apple juice is reported for
      the first time. In samples with distinct off-flavor, 2-isopropyl-3
      methoxypyrazine, 2-isobutyl-3-methoxypyrazine, 2-methylisoborneol, 1-octen-3-ol,
      fenchyl alcohol, geosmin, and guaiacol as well as 2,6-dibromophenol were
      determined in concentrations higher than the detection threshold.

PMID- 16881706
TI  - Flavor improvement in pork from barrows and gilts via inhibition of intestinal
      skatole formation with resistant potato starch.
AB  - Skatole originates from microbial processing of tryptophan in the large intestine
      of pigs and accumulates in adipose tissue. Formation may be inhibited by the anti
      apoptotic function of butyrate formed out of raw potato starch. Two groups of
      pigs (each consisting of gilts and barrows) were fed from 30 to 110 kg life
      weight either a conventional diet (controls; n = 35) or an isocaloric diet
      containing 300 g of raw potato starch/kg of body weight (RS; n = 34). Skatole
      concentrations were measured in colon content, blood, and adipose tissue. Odor of
      cooked meat samples was evaluated by a test panel. RS reduced concentrations in
      colon content and blood plasma (P < 0.001). Back fat concentrations were
      decreased significantly from 25 to 1.40 ng/g (barrows; P < 0.001) and from 40 to
      9 ng/g (gilts; P < 0.001). Odor rating (scale of 1-5 from very unpleasant to very
      pleasant) was 3.07 for low skatole concentrations and 2.66 for both medium and
      high skatole concentrations (P < 0.05).

PMID- 16881707
TI  - Structure-taste relationships for disubstituted phenylsulfamate tastants using
      classification and regression tree (CART) analysis.
AB  - Forty-two new disubstituted phenylsulfamates have been synthesized, and 30 of
      these have been combined with 40 already available from earlier work to create a
      training database of 70 compounds. On the basis of panel taste data these were
      divided into three categories, N (nonsweet), N/S (nonsweet/sweet), and (S) sweet,
      and a "sweetness value" or weighting was also calculated for each compound. Using
      these 70 compounds as a training set and a series of nine predictors derived from
      Corey-Pauling-Koltun (CPK) models, calculated from the PC SPARTAN PRO program and
      Hammett sigma values taken from the literature, a classification and regression
      tree analysis (CART) was carried out leading to a regression tree that correctly
      classified 62 of the 70 compounds (89% overall correct classification). The
      tree's predictive ability varies for the different taste categories, and for
      nonsweet compounds it is virtually 100%; for nonsweet/sweet compounds it is 66%,
      and for sweet compounds it is approximately 75%. This tree correctly predicted
      taste categories for 10 compounds from a test set of 12 randomly selected from
      among the 42 new compounds (83% correct classification). Therefore, it can be
      used with a good degree of confidence to predict the tastes of disubstituted
      phenylsulfamates. For the design of new sweeteners, appropriate values or ranges
      of the descriptors are derived.

PMID- 16881708
TI  - Physicochemical properties of native and recombinant mungbean (Vigna radiata L.
      Wilczek) 8S globulins and the effects of the N-linked glycans.
AB  - We have previously cloned and characterized the cDNAs of three isoforms of the 8S
      globulin of mungbean, expressed the major 8Salpha isoform in Escherichia coli,
      and purified and successfully crystallized it (Bernardo, A. E. N.; Garcia, R. N.;
      Adachi, M.; Angeles, J. G. C.; Kaga, A; Ishimoto, M.; Utsumi, S.; Tecson-Mendoza,
      E. M. J. Agric. Food Chem. 2004, 52, 2552-2560). Herein, we report the
      physicochemical and emulsifying properties of the native 8S and recombinant
      8Salpha globulin or vicilin. The circular dichroism spectra analysis of the
      native 8S and recombinant 8Salpha globulins revealed that the recombinant 8Salpha
      formed a secondary structure close to that of the native 8S. Further, gel
      filtration analysis showed that 8Salpha was able to assemble into trimers. The
      native 8S and recombinant 8Salpha globulins were soluble at pH 3.4 and at pH 7.4
      9.0 at low ionic strength, mu = 0.08. Interestingly, the native 8S was more
      soluble at pH 7.0 and pH 7.4 than the recombinant 8Salpha at mu = 0.08. Both
      forms were very soluble at pH 3.4-9.0 at high ionic strength, mu = 0.50. The
      native form exhibited a higher T(m) (69.2, 79.5, and 83.8 degrees C) than the
      recombinant form (65.6, 71.6, 77.5 degrees C) at mu = 0.1, 0.2, and 0.5,
      respectively. The recombinant form was found to have greater surface
      hydrophobicity than the native form. There was little difference in the
      emulsifying ability between the native 8S and 8Salpha at pH 3.4 and pH 7.6. The
      results indicate that the presence of N-linked glycans is not essential in the
      assembly and stable conformation of the mungbean vicilin. However, the N-linked
      glycans might have contributed to the higher solubility at low ionic strength,
      greater thermal stability, and decreased surface hydrophobicity of the native
      vicilin as compared to the recombinant 8Salpha. On the other hand, the N-linked
      glycans showed little effect on the emulsifying ability of the protein.

PMID- 16881709
TI  - Hydrogenation and interesterification effects on the oxidative stability and
      melting point of soybean oil.
AB  - Soybean oil with an iodine value of 136 was hydrogenated to have iodine values of
      126 and 117. The soybean oils with iodine values of 136, 126, and 117 were
      randomly interesterified using sodium methoxide. The oxidative stabilities of the
      hydrogenated and/or interesterified soybean oils were evaluated by measuring the
      headspace oxygen content by gas chromatography, and the induction time was
      measured using Rancimat. The melting points of the oils were evaluated by
      differential scanning calorimetry. Duncan's multiple range test of the headspace
      oxygen and induction time showed that hydrogenation increased the headspace
      oxygen content and induction time at alpha = 0.05. Interesterification decreased
      the headspace oxygen and the induction time for the soybean oils with iodine
      values of 136, 126, and 117 at alpha = 0.05. Hydrogenation increased the melting
      points as the iodine value decreased from 136 and 126 to 117 at alpha = 0.05. The
      random interesterification increased the melting points of soybean oils with
      iodine values of 136, 126, and 117 at alpha = 0.05. The combined effects of
      hydrogenation and interesterification increased the oxidative stability of
      soybean oil at alpha = 0.05 and the melting point at alpha = 0.01. The optimum
      combination of hydrogenation and random interesterification can improve the
      oxidative stability and increase the melting point to expand the application of
      soybean oil in foods.

PMID- 16881710
TI  - Effects, quenching mechanisms, and kinetics of water soluble compounds in
      riboflavin photosensitized oxidation of milk.
AB  - To protect the nutrient and flavor stability of milk under light, the effects of
      0, 0.01, 0.03, and 0.05 M 1,4-diazabicyclo[2,2,2]octane (DABCO) and 2,5
      dimethylfuran (DMF) on the riboflavin photosensitized oxidation of milk were
      studied. The oxidation of milk was studied by measuring the headspace oxygen in
      sample bottles after 3 h of light exposure at 3000 lux. As the concentration of
      DABCO and DMF, which are water soluble compounds, increased in the sample from 0,
      0.01, and 0.03 to 0.05 M, the depleted headspace oxygen content significantly
      decreased (P < 0.05). Steady state kinetic studies of singlet oxygen oxidation
      showed that the antioxidant activity of DABCO and DMF was due to singlet oxygen
      quenching. The reaction rate constant of singlet oxygen with milk fat was 8.1 x
      10(5) M(-1) s(-1). Total singlet oxygen quenching rates of DABCO and DMF were 1.5
      x 10(7) and 2.6 x 10(7) M(-1) s(-1), respectively. DABCO and DMF could be used to
      slow the reaction between singlet oxygen and milk components to protect
      nutrients, especially riboflavin, and to improve the oxidative stability of milk
      fat during storage or processing under light.

PMID- 16881711
TI  - Semi-mechanistic partial buffer approach to modeling pH, the buffer properties,
      and the distribution of ionic species in complex solutions.
AB  - In many biological science and food processing applications, it is very important
      to control or modify pH. However, the complex, unknown composition of biological
      media and foods often limits the utility of purely theoretical approaches to
      modeling pH and calculating the distributions of ionizable species. This paper
      provides general formulas and efficient algorithms for predicting the pH,
      titration, ionic species concentrations, buffer capacity, and ionic strength of
      buffer solutions containing both defined and undefined components. A flexible,
      semi-mechanistic, partial buffering (SMPB) approach is presented that uses local
      polynomial regression to model the buffering influence of complex or undefined
      components in a solution, while identified components of known concentration are
      modeled using expressions based on extensions of the standard acid-base theory.
      The SMPB method is implemented in a freeware package, (pH)Tools, for use with
      Matlab. We validated the predictive accuracy of these methods by using strong
      acid titrations of cucumber slurries to predict the amount of a weak acid
      required to adjust pH to selected target values.

PMID- 16881712
TI  - Polymorphic transformation in mixtures of high- and low-melting fractions of milk
      fat.
AB  - The kinetics of crystallization of high-melting fraction (HMF) and a mixture of
      40% HMF and 60% low-melting fraction (LMF) of milk fat were studied at 5 degrees
      C by time-resolved in-situ synchrotron X-ray diffraction. HMF crystallized in the
      alpha polymorph, had a longer lifetime than the ones previously reported in pure
      milk fat, and was almost completely solid. The HMF/LMF mixture crystallized
      initially in the alpha form and transformed into the beta' polymorph, with a
      solid fat content much lower than that of HMF. The polymorphic change was
      therefore attributed to a delayed sudden formation of beta' mixed crystals from
      the uncrystallized melt. These findings are important for the food industry and
      as fundamental knowledge to improve our understanding of the origin of the
      macroscopic physical properties of solid milk fat fractions used in many
      manufacturing processes.

PMID- 16881713
TI  - Effects of enzymatic deamidation by protein-glutaminase on structure and
      functional properties of wheat gluten.
AB  - Protein-glutaminase (PG) purified from Chryseobacterium proteolyticum was used to
      investigate its deamidation effects on wheat gluten. Water-insoluble gluten was
      able to be deamidated to the extent of deamidation degree (DD) 72% in 200 mM
      sodium phosphate buffer (pH 7) at 40 degrees C for 30 h. Sodium dodecyl sulfate
      polyacrylamide gel electrophoresis exhibited an upper shift of gluten bands with
      only deamidation for 1.5-2.0 h (DD 35-45%) compared to the bands of nondeamidated
      gluten. Results of Fourier transform infrared analysis revealed alterations in
      secondary structure of gluten by PG deamidation. The assignment within amide I
      region showed decreases in both inter- (around 1695 cm(-1)) and intramolecular
      beta-sheets (around 1680 cm(-1)) by deamidation suggesting the deterioration of
      the aggregation ability of gluten molecules. Solubility and emulsification
      properties of gluten at pH 7 were improved by deamidation, while both properties
      at pH 3 were deteriorated by deamidation. Enzyme-linked immunosorbent assay
      identified that allergenicity of deamidated gluten as compared to the
      nondeamidated cohorts was decreased remarkably as the deamidation time was
      prolonged.

PMID- 16881714
TI  - Supercritical fluid extraction of limonoid glucosides from grapefruit molasses.
AB  - Limonoid glucosides (primarily limonin 17-beta-D-glucopyranoside, LG) were
      extracted from grapefruit molasses by supercritical fluid extraction using a
      supercritical carbon dioxide-ethanol (SC CO(2)-ethanol) system. Extraction
      conditions to maximize the yield of LG were determined by varying pressure,
      temperature, ethanol concentration, and extraction time. The highest yield of LG
      at 0.61 mg/g molasses was obtained at a pressure 48.3 MPa, a temperature of 50
      degrees C, 10% ethanol (X(Eth) = 0.1), and 40 min of extraction time at a flow
      rate of 5.0 L/min. The results demonstrated that SC CO(2) extraction of limonoid
      glucosides from grapefruit molasses has practical significance for commercial
      production.

PMID- 16881715
TI  - Functional and structural properties of 2S soy protein in relation to other
      molecular protein fractions.
AB  - The purpose of this investigation is to develop a better understanding of the
      structure-function relationship of the 2S fraction of soy protein that has not
      been considered in earnest by the research community. Defatted soy flour was used
      to extract the three major fractions of the protein (2S, 7S, and 11S). It was
      found that 2S exhibits better foaming and emulsification properties than the
      other two molecular fractions. Work was extended to structural properties, which
      were monitored using spectrophotometry, atomic force microscopy, scanning
      electron microscopy, small-deformation dynamic oscillation on shear, and large
      deformation compression testing. An experimental protocol utilizing glucono-delta
      lactone (GDL), GDL with N-ethylmaleimide, or GDL with urea was capable of
      identifying the nature of molecular interactions responsible for gelation.
      Surprisingly, it was found that in the initial stages of structure formation, 2S
      fared better than 7S, with 11S exhibiting the highest rates of aggregation. Given
      time, however, 7S produced a firmer network with a better water-holding capacity
      than that of 2S. Non-covalent interactions, as opposed to disulfide bridging,
      were found to be largely responsible for the changing functionality of the
      molecular fractions throughout the experimentation from the formation of a
      vestigial structure to that of a mature gel.

PMID- 16881716
TI  - Quantitation of volatiles and nonvolatile acids in an extract from coffee
      beverages: correlation with antioxidant activity.
AB  - The antioxidant activities of a commercial brewed coffee were investigated by
      measuring malonaldehyde (MA) formation from oxidized cod liver oil using a gas
      chromatographic method (MA-GC assay) and a thiobarbituric acid method (TBA
      assay). The highest antioxidant activity obtained by the MA-GC assay was from
      regular whole brewed coffee (97.8%) at a level of 20%, and the highest
      antioxidant activity obtained by the TBA assay was from decaffeinated whole
      brewed coffee (96.6%) at a level of 5%. Among 31 chemicals identified in a
      dichloromethane extract, guaiacol, ethylguaiacol, and vinylguaiacol exhibited
      antioxidant activities, which were comparable to that of alpha-tocopherol. Among
      nine chlorogenic acids (three caffeoylquinic acids, three feruloylquinic acids,
      and three dicaffeoylquinic acids) identified, 5-caffeoylquinic acid contained the
      greatest amount both in regular (883.5 microg/mL) and in decaffeinated (1032.6
      microg/mL) coffees; it exhibited 24.5% activity by the MA-GC assay and 45.3%
      activity by the TBA assay at a level of 10 microg/mL. Caffeic and ferulic acids
      showed moderate antioxidant activities in both assays.

PMID- 16881717
TI  - Antioxidant activity of zein hydrolysates in a liposome system and the possible
      mode of action.
AB  - Maize zein was hydrolyzed for 0.5-5 h by alcalase or papain. Protein solubility
      increased (P < 0.05) with the degree of hydrolysis (DH) and was higher for
      alcalase-hydrolyzed zein than for papain-hydrolyzed zein. The zein hydrolysates
      with both enzymes consisted mostly of small peptides or amino acids nondetectable
      by 15% acrylamide gel electrophoresis. Alcalase-hydrolyzed zein exhibited a
      stronger (P < 0.05) antioxidant activity than papain-hydrolyzed zein, as
      indicated by peroxide and thiobarbituric acid-reactive substance values in a
      liposome-oxidizing system. Zein hydrolysates possessed strong Cu(2+) chelation
      ability and marked reducing power, both of which were accentuated with hydrolysis
      time. The protein hydrolysates also showed strong radical-scavenging ability,
      which was not influenced by hydrolysis time. The antioxidant activity of alcalase
      hydrolyzed zein at some specific low concentrations was close or comparable to
      those of butylated hydroxyanisole, alpha-tocopherol, and ascorbate. Although
      intact zein displayed an antioxidative effect, it was far less potent than
      hydrolyzed zein. The results demonstrated that enzyme-hydrolyzed zein can act as
      a metal ion chelator or a hydrogen donor, as well as a radical stabilizer to
      inhibit lipid oxidation. The effectiveness of the protein hydrolysates appeared
      to depend on both the concentration and the peptide/amino acid composition of the
      soluble protein fraction.

PMID- 16881718
TI  - Antioxidant mechanism studies on ferulic acid: identification of oxidative
      coupling products from methyl ferulate and linoleate.
AB  - In our studies of the chain-breaking antioxidant mechanism of natural phenols in
      food components, ferulic acid, a phenolic acid widely distributed in edible
      plants, especially grain, was investigated. The radical oxidation reaction of a
      large amount of ethyl linoleate in the presence of the methyl ester of ferulic
      acid produced four types of peroxides as radical termination products. The
      isolation and structure determination of the peroxides revealed that they had
      tricyclic structures which consisted of ethyl linoleate, methyl ferulate, and
      molecular oxygen. Based on the formation pathway of the products, a radical
      scavenging reaction occurred at the 3'-position of the ferulate radical with the
      four types of peroxyl radicals of ethyl linoleate. The produced peroxides
      subsequently underwent intramolecular Diels-Alder reaction to afford stable
      tricyclic peroxides.

PMID- 16881719
TI  - Inhibitory effects of Orostachys japonicus extracts on the formation of N
      nitrosodimethylamine.
AB  - In Korea, Orostachys japonicus has been used traditionally as a drug and health
      food. The aim of this study was to investigate possible inhibitory effects of O.
      japonicus extracts on the formation of N-nitrosodimethylamines (NDMA). Chloroform
      extraction was the most effective method for recovering the highest number of
      phenolic compounds and flavonoids; in these extracts the greatest nitrite
      scavenging activity and inhibition of NDMA formation occurred at pH 2.5. The
      chloroform extract was separated into 10 fractions (J1-J10); fraction J4
      inhibited NDMA formation by 90.1 +/- 0.4%. This fraction was then separated into
      five subfractions (J4-1-J4-5) using a silica gel column. Subfractions J4-2 [(+)
      catechin] and J4-4 (3,4-dihdroxybenzoic acid) inhibited NDMA formation by 89.5 +/
      0.9 and 77.6 +/- 0.8%, respectively.

PMID- 16881720
TI  - Enrichment of refined olive oil with phenolic compounds: evaluation of their
      antioxidant activity and their effect on the bitter index.
AB  - The study of the antioxidant effects of biophenolic compounds is supported by the
      current interest in natural products and the ongoing replacement of synthetic
      antioxidants by natural antioxidants from plant sources. Olives and olive oil,
      especially extra virgin olive oil, contain a variety of bioactive compounds
      (phytochemicals) widely considered to be potentially beneficial for health. This
      research was focused on evaluating the antioxidant activity of the enriched
      refined olive oil to discover a possible functional food application. Different
      concentrations of individual and combined phenolic compounds were added to the
      refined olive oil as lipid matrix, and the antioxidant activity expressed as
      oxidative stability in hours was determined by using the Rancimat method.
      Additionally, the bitter index was evaluated to assess the effect of the
      enrichment in relation to the organoleptic quality. The results showed that the
      antioxidant activity depends on the concentration of the phenol used for the
      assay and the chemical structure. In general, the most positive effects were
      observed in 3,4-dihydroxy and 3,4,5-trihydroxy structures linked to an aromatic
      ring that conferred to the moiety a higher proton dislocation, thus facilitating
      the scavenging activity.

PMID- 16881721
TI  - Seven new aminoacyl sugars in Ipomoea batatas.
AB  - An analysis of the polar extracts from sweet potato Ipomoea batatas
      (Convolvulaceae) led to the isolation of seven unknown aminoacyl sugars. On the
      basis of 1D, 2D NMR, and mass spectrometry data, the structures of the compounds
      were elucidated as: beta-D-fructofuranosyl-(2 --> 1)-alpha-D-[2-O-valyl]
      glucopyranoside (1), beta-D-fructofuranosyl-(2 --> 1)-alpha-D-[2-O-tyrosyl]
      glucopyranoside (2), beta-D-fructofuranosyl-(2 --> 1)-alpha-D-[2-O-threonyl]
      glucopyranoside (3), beta-D-fructofuranosyl-(2 --> 1)-alpha-D-[2-O-hystidyl]
      glucopyranoside (4), 2-beta-D-fructofuranosyl-(2 --> 1)-alpha-D-[2-O-alanyl]
      glucopyranoside (5), beta-D-fructofuranosyl-(2 --> 1)-alpha-D-[2-O-tryptophanyl]
      glucopyranoside (6), and beta-D-fructofuranosyl-(2 --> 1)-alpha-D-[2-O-glycyl]
      glucopyranoside (7).

PMID- 16881722
TI  - Profiling of carotenoids in tomato juice by one- and two-dimensional NMR.
AB  - Epidemiological data have shown a link between dietary intake of tomatoes and
      tomato products (rich in carotenoids) and a decreased risk of chronic diseases.
      The carotenoid profile in tomato products depends on tomato variety as well as
      the thermal conditions used in processing. The final carotenoid profile may
      affect the bioaccessibility and bioavailability of these biomolecules. Therefore,
      nondestructive, reliable methods are needed to characterize the structural and
      stereochemical variation of carotenoids. CDCl(3) rapid extraction was used to
      extract carotenoids from tomato juice as an alternative rapid procedure that
      minimizes solvents and time consumption prior to NMR analysis. The profile of
      these biomolecules was characterized by application of high-resolution
      multidimensional NMR techniques using a cryogenic probe. The combination of
      homonuclear and heteronuclear two-dimensional NMR techniques served to identify
      (all-E)-, (5Z)-, (9Z)-, and (13Z)-lycopene isomers and other carotenoids such as
      (all-E)-beta-carotene and (15Z)-phytoene dissolved in the extracted lipid
      mixture. The use of one-dimensional NMR enabled the rapid identification of
      lycopene isomers, thereby minimizing further isomerization of (all-E)-lycopene as
      compared to HPLC data. On the basis of the assignments accomplished, the
      carotenoid profile of typical tomato juice was successfully determined with
      minimal purification procedures.

PMID- 16881723
TI  - Chemical conversion of alpha-amino acids into alpha-keto acids by 4,5-epoxy-2
      decenal.
AB  - The comparative formation of phenylalanine and phenylpyruvic acid in the reaction
      of 4,5-epoxy-2-decenal with phenylalanine was studied to determine whether
      epoyalkenals may also degrade amino acids without producing their
      decarboxylation. Both compounds were produced in the reaction to an extent that
      depended on the reaction pH, the amount of lipid oxidation product, and the
      reaction time and temperature. The optimum pH was 3 for producing both carbonyl
      derivatives, and the amount of both compounds increased linearly with the amount
      of epoxyalkenal present in the reaction mixture. In addition, phenylpyruvic acid
      was produced to a higher extent than phenylacetaldehyde at 37 degrees C. However,
      at 60 degrees C the degradation of phenylpyruvic acid was observed and
      phenylacetaldehyde was usually found to a higher extent than the alpha-keto acid
      in the overnight-incubated reaction mixtures. The degradation of phenylpyruvic
      acid produced benzaldehyde and phenylacetaldehyde. All these results suggest that
      epoxyalkenals can not only degrade amino acids by a Strecker-type mechanism but
      convert them into their corresponding alpha-keto acids. This new reaction may be
      an alternative chemical route for the formation in foods of alpha-keto acids,
      which can later participate in the generation of important amino acid-derived
      flavor compounds.

PMID- 16881724
TI  - Daily intake of arsenic, cadmium, mercury, and lead by consumption of edible
      marine species.
AB  - The daily intake of arsenic (As), cadmium (Cd), mercury (Hg), and lead (Pb)
      through the consumption of 14 edible marine species by the general population of
      Catalonia, Spain, was estimated. Health risks derived from this intake were also
      assessed. In March-April 2005, samples of sardine, tuna, anchovy, mackerel,
      swordfish, salmon, hake, red mullet, sole, cuttlefish, squid, clam, mussel, and
      shrimp were randomly acquired in six cities of Catalonia. Concentrations of As,
      Cd, Hg, and Pb were determined by ICP-MS. On the basis of recent fish and seafood
      consumption data, the daily intake of these elements was calculated for eight
      age/sex groups of the population. The highest As concentrations were found in red
      mullet, 16.6 microg/g of fresh weight, whereas clam and mussel (0.14 and 0.13
      microg/g of fresh weight, respectively) were the species with the highest Cd
      levels. In turn, swordfish (1.93 microg/g of fresh weight) and mussel and salmon
      (0.15 and 0.10 microg/g of fresh weight) showed the highest concentrations of Hg
      and Pb, respectively. The highest metal intake through fish and seafood
      consumption corresponded to As (217.7 microg/day), Cd (1.34 microg/day), and Pb
      (2.48 microg/day) for male seniors, whereas that of Hg was observed in male
      adults (9.89 microg/day). The daily intake through fish and seafood consumption
      of these elements was compared with the provisional tolerable weekly intakes
      (PTWI). The intakes of As, Cd, Pb, and total Hg by the population of Catalonia
      were below the respective PTWI values. However, the estimated intake of
      methylmercury for boys, 1.96 microg/kg/week, was over the PTWI.

PMID- 16881725
TI  - Maize (Zea mays L.) genetic factors for preventing fumonisin contamination.
AB  - Fusarium moniliforme and Fusarium proliferatum are the most frequently isolated
      fungi from maize (Zea mays L.) in Spain. Both Fusarium species produce toxins
      potentially dangerous for animals and humans, the fumonisins being the most
      significant of those toxins. White maize is preferred for human consumption, and
      extra care should be taken to avoid kernel mycotoxin contamination. The
      objectives of this study were to identify and quantify kernel infection by
      Fusarium spp. and contamination by fumonisin on white maize hybrids, to search
      for white maize sources of resistance to infection by Fusarium spp. and mycotoxin
      contamination, and to preliminarily study the genetics involved in such
      resistances. Ten F(1) single crosses derived from a diallel mating design among
      five white maize inbreds were evaluated in a randomized complete block design
      with three replications in 2002 at two locations. Fusarium verticilloides and F.
      proliferatum were detected on kernels of white maize hybrids cultivated in
      northwestern Spain. No differences in fungal infection were found among maize
      genotypes, but differences in fumonisin contamination were significant and could
      be related, in part, to differences in husk tightness. Among the genotypes
      studied, general combining ability (GCA) effects were the most important for
      resistance to fumonisin contamination. Inbreds EP10 and EC22 showed the most
      favorable GCA effects for husk tightness and fumonisin content, and the cross
      between them, EP10 x EC22, had the most favorable specific combining ability
      (SCA) effect for husk tightness. Inbreds EP10 and EC22 showed favorable GCA
      effects for fumonisin contamination and husk tightness, and the cross EP10 x EC22
      was the only one with an average fumonisin level below 1 mug/g. Although this
      should be confirmed with more extensive studies, white maize inbreds developed
      from white maize landraces could be sources of resistance to fumonisin
      contamination.

PMID- 16881726
TI  - Incidence of Fusarium verticillioides and levels of fumonisins in corn from main
      production areas in Iran.
AB  - A total of 52 corn samples collected in 2000 from four main corn production
      provinces of Iran (Fars, Kermanshah, Khuzestan, and Mazandaran) were analyzed for
      contamination with Fusarium verticillioides and fumonisins (FB(1), FB(2), FB(3),
      and 3-epi-FB(3)). The mean incidence of F. verticillioides (percent of kernels
      infected) for these four areas was 26.7, 21.4, 24.9, and 59.0%, respectively. The
      incidence in Mazandaran was significantly (p < 0.05) above that of the other
      areas. All samples from Mazandaran were contaminated with fumonisins with a mean
      level of total fumonisins of 10674 microg/kg. In contrast, the incidence of
      fumonisin contamination above 10 microg/kg was 53 (8/15), 42 (5/12), and 57%
      (8/14) in the samples from Fars, Kermanshah, and Khuzestan, respectively, and the
      corresponding mean total fumonisin levels were 215, 71, and 174 microg/kg,
      respectively. No statistical differences (p > 0.05) were observed in the
      fumonisin levels of the corn samples from these three provinces, which were
      significantly (p < 0.05) lower than the fumonisin contamination in samples from
      Mazandaran.

PMID- 16881727
TI  - The City Initiative for Newborn Health.

PMID- 16881728
TI  - How do intellectual property law and international trade agreements affect access
      to antiretroviral therapy?

PMID- 16881729
TI  - Reducing the impact of the next influenza pandemic using household-based public
      health interventions.
AB  - BACKGROUND: The outbreak of highly pathogenic H5N1 influenza in domestic poultry
      and wild birds has caused global concern over the possible evolution of a novel
      human strain [1]. If such a strain emerges, and is not controlled at source
      [2,3], a pandemic is likely to result. Health policy in most countries will then
      be focused on reducing morbidity and mortality. METHODS AND FINDINGS: We estimate
      the expected reduction in primary attack rates for different household-based
      interventions using a mathematical model of influenza transmission within and
      between households. We show that, for lower transmissibility strains [2,4], the
      combination of household-based quarantine, isolation of cases outside the
      household, and targeted prophylactic use of anti-virals will be highly effective
      and likely feasible across a range of plausible transmission scenarios. For
      example, for a basic reproductive number (the average number of people infected
      by a typically infectious individual in an otherwise susceptible population) of
      1.8, assuming only 50% compliance, this combination could reduce the infection
      (symptomatic) attack rate from 74% (49%) to 40% (27%), requiring peak quarantine
      and isolation levels of 6.2% and 0.8% of the population, respectively, and an
      overall anti-viral stockpile of 3.9 doses per member of the population. Although
      contact tracing may be additionally effective, the resources required make it
      impractical in most scenarios. CONCLUSIONS: National influenza pandemic
      preparedness plans currently focus on reducing the impact associated with a
      constant attack rate, rather than on reducing transmission. Our findings suggest
      that the additional benefits and resource requirements of household-based
      interventions in reducing average levels of transmission should also be
      considered, even when expected levels of compliance are only moderate.

PMID- 16881730
TI  - Creating and validating an algorithm to measure AIDS mortality in the adult
      population using verbal autopsy.
AB  - BACKGROUND: Vital registration and cause of death reporting is incomplete in the
      countries in which the HIV epidemic is most severe. A reliable tool that is
      independent of HIV status is needed for measuring the frequency of AIDS deaths
      and ultimately the impact of antiretroviral therapy on mortality. METHODS AND
      FINDINGS: A verbal autopsy questionnaire was administered to caregivers of 381
      adults of known HIV status who died between 1998 and 2003 in Manicaland, eastern
      Zimbabwe. Individuals who were HIV positive and did not die in an accident or
      during childbirth (74%; n = 282) were considered to have died of AIDS in the gold
      standard. Verbal autopsies were randomly allocated to a training dataset (n =
      279) to generate classification criteria or a test dataset (n = 102) to verify
      criteria. A rule-based algorithm created to minimise false positives had a
      specificity of 66% and a sensitivity of 76%. Eight predictors (weight loss,
      wasting, jaundice, herpes zoster, presence of abscesses or sores, oral
      candidiasis, acute respiratory tract infections, and vaginal tumours) were
      included in the algorithm. In the test dataset of verbal autopsies, 69% of deaths
      were correctly classified as AIDS/non-AIDS, and it was not necessary to invoke a
      differential diagnosis of tuberculosis. Presence of any one of these criteria
      gave a post-test probability of AIDS death of 0.84. CONCLUSIONS: Analysis of
      verbal autopsy data in this rural Zimbabwean population revealed a distinct
      pattern of signs and symptoms associated with AIDS mortality. Using these signs
      and symptoms, demographic surveillance data on AIDS deaths may allow for the
      estimation of AIDS mortality and even HIV prevalence.

PMID- 16881732
TI  - Interphase chromosome positioning affects the spectrum of radiation-induced
      chromosomal aberrations.
AB  - In interphase, chromosomes occupy defined nuclear volumes known as chromosome
      territories. To probe the biological consequences of the described nonrandom
      spatial positioning of chromosome territories in human lymphocytes, we performed
      an extensive FISH-based analysis of ionizing radiation-induced interchanges
      involving chromosomes 1, 4, 18 and 19. Since the probability of exchange
      formation depends strongly on the spatial distance between the damage sites in
      the genome, a preferential formation of exchanges between proximally positioned
      chromosomes is expected. Here we show that the spectrum of interchanges deviates
      significantly from one expected based on random chromosome positioning. Moreover,
      the observed exchange interactions between specific chromosome pairs as well as
      the interactions between homologous chromosomes are consistent with the proposed
      gene density-related radial distribution of chromosome territories. The
      differences between expected and observed exchange frequencies are more
      pronounced after exposure to densely ionizing neutrons than after exposure to
      sparsely ionizing X rays. These experiments demonstrate that the spatial
      positioning of interphase chromosomes affects the spectrum of chromosome
      rearrangements.

PMID- 16881731
TI  - Conjunctival FOXP3 expression in trachoma: do regulatory T cells have a role in
      human ocular Chlamydia trachomatis infection?
AB  - BACKGROUND: Trachoma, caused by ocular infection with Chlamydia trachomatis,
      remains the leading infectious cause of blindness and in 2002 was responsible for
      3.6% of total global blindness. Although transmission can be successfully
      interrupted using antibiotics and improvements in public and personal hygiene,
      the long-term success of the control programmes advocated by the World Health
      Organization are still uncertain. For the complete control and prevention of
      trachoma, a vaccine would be highly desirable. Currently there are no licensed
      vaccines for trachoma, and no human vaccine trials have been conducted since the
      1960s. A barrier to new attempts to design and introduce a vaccine is the
      identification of immunologic correlates of protective immunity or
      immunopathology. We studied important correlates of the immune response in a
      trachoma-endemic population in order to improve our knowledge of this disease.
      This is essential for the successful development of a vaccine against both ocular
      and genital C. trachomatis infection. METHODS AND FINDINGS: We used quantitative
      real-time PCR for C. trachomatis 16S rRNA to identify conjunctival infection. The
      expression of IFN-gamma, IDO, IL-10, and FOXP3 mRNA transcripts was measured. We
      evaluated the role of immune effector and regulatory responses in the control of
      chlamydial infection and in the resolution of clinical signs of trachoma in
      endemic communities in Gambia. All host transcripts examined were detectable even
      in normal conjunctiva. The levels of these transcripts were increased, compared
      to normal uninfected conjunctiva, when infection was detected, with or without
      clinical disease signs. Interestingly, when clinical disease signs were present
      in the absence of infection, the expression of a regulatory T cell transcription
      factor, FOXP3, remained elevated. CONCLUSIONS: There is evidence of an increase
      in the magnitude of the local anti-chlamydial cytokine immune responses with age.
      This increase is coupled to a decline in the prevalence of infection and active
      trachoma, suggesting that effective adaptive immunity is acquired over a number
      of years. The anti-chlamydial and inflammatory immune response at the
      conjunctival surface, which may control chlamydial replication, is closely
      matched by counter inflammatory or regulatory IL-10 expression. Differences in
      the level of FOXP3 expression in the conjunctiva may indicate a role for
      regulatory T cells in the resolution of the conjunctival immune response, which
      is important in protection from immunopathology. However, the expression of
      cytokines that control chlamydial replication and those that regulate the
      conjunctival immune response is not simply juxtaposed; the interaction between
      the infection and the clinical disease process is therefore more complex.

PMID- 16881733
TI  - Protection against adverse biological effects induced by space radiation by the
      Bowman-Birk inhibitor and antioxidants.
AB  - This study was undertaken to evaluate the protective effects of the soybean
      derived Bowman-Birk inhibitor (BBI), BBI concentrate (BBIC) and/or antioxidants
      against the adverse biological effects induced by space radiation in cultured
      human epithelial cells. The effects of BBI, BBIC and a combination of ascorbic
      acid, co-enzyme Q10, L-selenomethionine (SeM) and vitamin E succinate on proton
      and HZE-particle [high-energy (high E) nuclei of heavier (high atomic number, Z)
      elements] radiation-induced cytotoxicity in MCF10 human breast epithelial cells
      and a phenotypic change associated with transformation in HTori-3 human thyroid
      epithelial cells were assessed with a clonogenic survival assay and a soft agar
      colony formation assay. The results demonstrate that BBIC and antioxidants are
      effective in protecting against space radiation-induced cytotoxicity in MCF10
      cells and BBI, BBIC and antioxidants are effective in protecting against a space
      radiation-induced phenotypic change associated with transformation of HTori-3
      cells.

PMID- 16881734
TI  - Mechanisms underlying production of double-strand breaks in plasmid DNA after
      decay of 125I-Hoechst.
AB  - Previously, the kinetics of strand break production by (125)I-labeled m-iodo-p
      ethoxyHoechst 33342 ((125)IEH) in supercoiled (SC) plasmid DNA had demonstrated
      that approximately 1 DSB is produced per (125)I decay both in the presence and
      absence of the hydroxyl radical scavenger DMSO. In these experiments, an
      (125)IEH:DNA molar ratio of 42:1 was used. We now hypothesize that this DSB yield
      (but not the SSB yield) may be an overestimate due to subsequent decays occurring
      in any of the 41 (125)IEH molecules still bound to nicked (N) DNA. To test our
      hypothesis, (125)IEH was incubated with SC pUC19 plasmids ((125)IEH:DNA ratio of
      approximately 3:1) and the SSB and DSB yields were quantified after the decay of
      (125)I. As predicted, the number of DSBs produced per (125)I decay is one-half
      that reported previously ( approximately 0.5 compared to approximately 1, +/-
      DMSO) whereas the number of SSBs ( approximately 3/(125)I decay) is similar to
      that obtained previously ( approximately 90% are generated by OH radicals).
      Direct visualization by atomic force microscopy confirms formation of L and N DNA
      after (125)IEH decays in SC DNA and supports the strand break yields reported.
      These findings indicate that although SSB production is independent of the number
      of (125)IEH bound to DNA, the DSB yield can be augmented erroneously by (125)I
      decays occurring in N DNA. Further analysis indicates that 17% of SSBs and 100%
      of DSBs take place within the plasmid molecule in which an (125)IEH molecule
      decays, whereas 83% of SSBs are formed in neighboring plasmid DNA molecules.

PMID- 16881735
TI  - Regeneration of megakaryocytopoiesis and thrombopoiesis in vitro from X
      irradiated human hematopoietic stem cells.
AB  - In the present study, we investigated whether X-irradiated hematopoietic stem
      cells can be induced to undergo megakaryocytopoiesis and thrombopoiesis in vitro
      using cytokine combinations that have been demonstrated to be effective for
      conferring increased survival on irradiated human CD34(+) megakaryocytic
      progenitor cells (colony-forming unit megakaryocytes; CFU-Meg), such as
      thrombopoietin (TPO), interleukin 3 (IL3), stem cell factor and FLT3 ligand.
      Culture of nonirradiated CD34(+) cells in serum-free medium supplemented with
      multiple cytokine combinations led to an approximately 200- to 600-fold increase
      in the total cell numbers by day 14 of culture. In contrast, the growth of X
      irradiated cells was observed to be one-sixth to one-tenth that of the
      nonirradiated cultures. Similarly, total megakaryocytes were increased by 50- to
      130-fold, while culture of X-irradiated cells yielded one-fourth to one-eighth of
      the control numbers. At this time, CD41(+) particles, which appeared to be
      platelets, were produced in the medium harvested from nonirradiated and
      irradiated cultures. Although radiation suppressed cell growth and
      megakaryocytopoiesis, there were no significant differences in thrombopoiesis
      between the two types of culture. These results suggest that X-irradiated CD34(+)
      cells can be induced to undergo nearly normal terminal maturation through
      megakaryocytopoiesis and thrombopoiesis by stimulation with appropriate cytokine
      combinations.

PMID- 16881736
TI  - Live attenuated Salmonella carrying platelet factor 4 cDNAs as radioprotectors.
AB  - To determine whether live attenuated Salmonella carrying platelet factor 4 cDNAs
      can protect mice from radiation damage, the attenuated Salmonella SL3261 was used
      as oral vector for targeted gene delivery. The recovery of mice receiving
      sublethal total-body irradiation (TBI) was investigated after the oral
      administration of attenuated Salmonella carrying cDNA for platelet factor 4 (PF4)
      or truncated PF4. This oral gene therapy protected mice from radiation damage
      after TBI. The number of bone marrow cells and high proliferative potential
      colony-forming cells (HPP-CFCs) increased significantly at day 7. Similarly, the
      administration of PF4 or PF4(17-70) protein also improved the survival of mice
      after TBI. Both PF4 gene therapy and protein administration accelerated
      hematopoietic recovery in vivo in mice after irradiation. In vitro, PF4 also
      promoted survival and proliferation of 5-fluorouracil-resistant hematopoietic
      stem/progenitor cells after irradiation. These data demonstrate a novel
      biological function of PF4 as a protector against radiation injury and suggest
      that attenuated Salmonella could be used in vivo as a PF4 DNA delivery vector in
      the management of radiation injury.

PMID- 16881737
TI  - Levels of antibodies to microorganisms implicated in atherosclerosis and of C
      reactive protein among atomic bomb survivors.
AB  - Although it has been suggested that cardiovascular disease incidence is increased
      among atomic bomb survivors, the existence of a causal relationship between
      radiation exposure and atherosclerosis is unclear. Microbial infections,
      including those caused by Chlamydia pneumoniae, Helicobacter pylori and
      cytomegalovirus, have recently been implicated in atherosclerosis. Since immune
      function is somewhat impaired among atomic bomb survivors, their immune defense
      against such infections might be diminished. To investigate this possibility, we
      measured antibody levels to the above microorganisms in the sera of survivors. We
      found that the levels of IgG and IgA antibodies to Chlamydia pneumoniae decreased
      significantly with radiation dose, whereas the levels of IgG antibodies to
      Helicobacter pylori or cytomegalovirus remained unchanged. The inflammation
      marker C-reactive protein was significantly and positively associated with level
      of antibodies to Chlamydia pneumoniae only in heavily exposed (>or=1000 mGy)
      survivors. These results may suggest that among atomic bomb survivors, immune
      response to Chlamydia pneumoniae is diminished and chronic inflammatory reactions
      related to Chlamydia pneumoniae infection are present.

PMID- 16881738
TI  - Childhood thyroid cancer, radiation dose from Chernobyl, and dose uncertainties
      in Bryansk Oblast, Russia: a population-based case-control study.
AB  - A population-based case-control study was conducted to estimate the radiation
      related risk of thyroid cancer in persons who were exposed in childhood to (131)I
      from the Chernobyl accident of April 26, 1986 and to investigate the impact of
      uncertainties in individual dose estimates. Included were all 66 confirmed cases
      of primary thyroid cancer diagnosed from April 26, 1986 through September 1998 in
      residents of Bryansk Oblast, Russia, who were 0-19 years old at the time of the
      accident, along with two individually matched controls for each case. Thyroid
      radiation doses, estimated using a semi-empirical model based on environmental
      contamination data and individual characteristics, ranged from 0.00014 Gy to 2.73
      Gy and had large uncertainties (median geometric standard deviation 2.2). The
      estimated excess relative risk (ERR) associated with radiation exposure, 48.7/Gy,
      was significantly greater than 0 (P = 0.00013) but had an extremely wide 95%
      confidence interval (4.8 to 1151/Gy). Adjusting for dose uncertainty nearly
      tripled the ERR to 138/Gy, although this was likely an overestimate due to
      limitations in the modeling of dose uncertainties. The radiation-related excess
      risk observed in this study is quite large, especially if the uncertainty of dose
      estimation is taken into account, but is not inconsistent with estimates
      previously reported for risk after (131)I exposure or acute irradiation from
      external sources.

PMID- 16881740
TI  - Therapeutic success of boron neutron capture therapy (BNCT) mediated by a
      chemically non-selective boron agent in an experimental model of oral cancer: a
      new paradigm in BNCT radiobiology.
AB  - The hypothesis of boron neutron capture therapy (BNCT) research has been that the
      short-range, high-linear energy transfer radiation produced by the capture of
      thermal neutrons by (10)B will potentially control tumor and spare normal tissue
      only if the boron compound selectively targets tumor tissue within the treatment
      volume. In a previous in vivo study of low-dose BNCT mediated by GB-10
      (Na(2)(10)B(10)H(10)) alone or combined with boronophenylalanine (BPA) in the
      hamster cheek pouch oral cancer model that was primarily designed to evaluate
      safety and feasibility, we showed therapeutic effects but no associated normal
      tissue radiotoxicity. In the present study, we evaluated the response of tumor,
      precancerous and normal tissue to high-dose BNCT mediated by GB-10 alone or
      combined with BPA. Despite the fact that GB-10 does not target hamster cheek
      pouch tumors selectively, GB-10-BNCT induced a 70% overall tumor response with no
      damage to normal tissue. (GB-10+BPA)-BNCT induced a 93% overall tumor response
      with no normal tissue radiotoxicity. Light microscope analysis showed that GB-10
      BNCT selectively damages tumor blood vessels, sparing precancerous and normal
      tissue vessels. In this case, selective tumor lethality would thus result from
      selective blood vessel damage rather than from selective uptake of the boron
      compound.

PMID- 16881739
TI  - Post-Chernobyl thyroid cancers in Ukraine. Report 2: risk analysis.
AB  - On April 26, 1986, the worst nuclear reactor accident to date occurred at the
      Chornobyl (Chernobyl) power plant in Ukraine. Millions of people in Ukraine,
      Belarus and Russia were exposed to radioactive nuclides, especially (131)I. Since
      then, research has been conducted on various subgroups of the exposed population,
      and it has been demonstrated that the large increase in thyroid cancer is related
      to the (131)I exposure. However, because of study limitations, quantified risk
      estimates are limited, and there remains a need for additional information. We
      conducted an ecological study to investigate the relationship between (131)I
      thyroid dose and the diagnosis of thyroid cancer in three highly contaminated
      oblasts in Northern Ukraine. The study population is comprised of 301,907 persons
      who were between the ages of 1 and 18 at the time of the Chornobyl accident and
      were living in 1,293 rural settlements in the three study oblasts. Twenty-four
      percent of the study population had individual thyroid dose estimates and the
      other 76% had "individualized" estimates of thyroid dose based on direct thyroid
      measurements taken from a person of the same age and gender living in the same or
      nearby settlement. Cases include 232 thyroid cancers diagnosed from January 1990
      through December 2001, and all were confirmed histologically. Dose-response
      analyses took into account differences in the rate of ultrasound examinations
      conducted in the three study oblasts. The estimated excess relative risk per gray
      was 8.0 (95% CI = 4.6-15) and the excess absolute risk per 10,000 person-year
      gray was estimated to be 1.5 (95% CI = 1.2-1.9). In broad terms, these estimates
      are compatible with results of other studies from the contaminated areas, as well
      as studies of external radiation exposure.

PMID- 16881741
TI  - No effects of radiofrequency radiation on 3-chloro-4-(dichloromethyl)-5-hydroxy
      2(5H)-furanone-induced tumorigenesis in female Wistar rats.
AB  - This study evaluated possible effects of radiofrequency (RF) radiation on
      tumorigenesis induced by the mutagen 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)
      furanone (MX) given in drinking water. Female Wistar rats aged 7 weeks at the
      beginning of the experiments were randomly divided into four groups of 72
      animals: a cage-control group and three MX-exposed groups (a daily average dose
      of 1.7 mg MX/kg body weight for 104 weeks), of which two were exposed to 900 MHz
      pulsed RF radiation and the third served as a sham-RF-radiation group. The RF
      radiation groups were exposed 2 h per day, 5 days per week for 104 weeks at
      nominal whole-body average SARs of 0.3 W/kg and 0.9 W/kg. Complete histopathology
      was performed on the rats of the three MX-exposed groups. The tumor types and
      incidences observed in the MX-exposed animals were similar to those reported
      earlier in MX-exposed female Wistar rats. RF radiation did not statistically
      significantly affect mortality or organ-specific incidence of any tumor type. The
      only statistically significant difference was an increase in the combined
      frequency of vascular tumors of the mesenteric lymph nodes in the high-RF
      radiation group compared to the sham-RF-radiation group. However, additional
      histopathological analysis of the cage-control animals suggested that this
      difference was due to unusually low frequency of this type of tumor in the sham
      RF-radiation group rather than a high frequency in the high-RF-radiation group.
      With respect to non-neoplastic findings, statistically significant differences
      between the RF-radiation groups and the sham-RF-radiation group were observed
      only for single findings in the lacrimal glands, lungs, liver and skin. Such
      changes are commonly seen in aged rats and were considered to be unrelated to RF
      radiation. The results of the present study do not support co-carcinogenic
      effects of low-level long-term RF-radiation exposure in rats.

PMID- 16881742
TI  - Exposure of cultured astroglial and microglial brain cells to 900 MHz microwave
      radiation.
AB  - The rapid rise in the use of mobile communications has raised concerns about
      health issues related to low-level microwave radiation. The head and brain are
      usually the most exposed targets in mobile phone users. In the brain, two types
      of glial cells, the astroglial and the microglial cells, are interesting in the
      context of biological effects from microwave exposure. These cells are widely
      distributed in the brain and are directly involved in the response to brain
      damage as well as in the development of brain cancer. The aim of the present
      study was to investigate whether 900 MHz radiation could affect these two
      different glial cell types in culture by studying markers for damage-related
      processes in the cells. Primary cultures enriched in astroglial cells were
      exposed to 900 MHz microwave radiation in a temperature-controlled exposure
      system at specific absorption rates (SARs) of 3 W/kg GSM modulated wave (mw) for
      4, 8 and 24 h or 27 W/kg continuous wave (cw) for 24 h, and the release into the
      extracellular medium of the two pro-inflammatory cytokines interleukin 6 (Il6)
      and tumor necrosis factor-alpha (Tnfa) was analyzed. In addition, levels of the
      astroglial cell-specific reactive marker glial fibrillary acidic protein (Gfap),
      whose expression dynamics is different from that of cytokines, were measured in
      astroglial cultures and in astroglial cell-conditioned cell culture medium at
      SARs of 27 and 54 W/kg (cw) for 4 or 24 h. No significant differences could be
      detected for any of the parameters studied at any time and for any of the
      radiation characteristics. Total protein levels remained constant during the
      experiments. Microglial cell cultures were exposed to 900 MHz radiation at an SAR
      of 3 W/kg (mw) for 8 h, and I16, Tnfa, total protein and the microglial
      reactivity marker ED-1 (a macrophage activation antigen) were measured. No
      significant differences were found. The morphology of the cultured astroglial
      cells and microglia was studied and appeared to be unaffected by microwave
      irradiation. Thus this study does not provide evidence for any effect of the
      microwave radiation used on damage-related factors in glial cells in culture.

PMID- 16881744
TI  - Mammalian cell killing by ultrasoft X rays and high-energy radiation: an
      extension of the MK model.
AB  - An alternate formulation of the microdosimetric-kinetic (MK) model is presented
      that applies to irradiation of mammalian cells with ultrasoft X rays as well as
      high-energy radiations of variable linear energy transfer (LET). Survival and DNA
      double-strand break measurements for V79 cells from the literature are examined
      to illustrate application of the model. It is demonstrated that the linear
      component of the linear-quadratic survival relationship (alpha) is enhanced
      because repairable potentially lethal lesions formed from a single ultrasoft X
      ray energy deposition event, when closer on average than for a single high-energy
      radiation event, are more likely to combine to form a lethal lesion. The
      quadratic component (beta) of the linear-quadratic survival relationship is
      increased because the potentially lethal lesions formed by ultrasoft X rays are
      created with greater efficiency than those of high-energy radiation. In addition,
      potentially lethal lesions from very low-energy carbon K-shell X rays may be
      enriched in structural forms that favor combination to form lethal lesions
      instead of repair. These features account for the increased effectiveness of
      killing of V79 cells by ultrasoft X rays compared to cobalt-60 gamma radiation.
      The importance of pairwise combination of potentially lethal lesions to form
      exchange chromosome aberrations that become lethal lesions is discussed. The
      extended MK model explains and reconciles differences between the MK model and
      the theory of dual radiation action on the one hand, and on the other, the view
      that variation in the RBE with radiation quality is explained by differences in
      energy deposition in nanometer- rather than micrometer-size volumes.

PMID- 16881743
TI  - Investigating the formation and growth of alpha-particle radiation-induced foci
      of altered hepatocytes: a model-based approach.
AB  - The effect of alpha-particle radiation on the formation and increase in volume of
      preneoplastic liver lesions was investigated in an animal experiment. Mice were
      divided into four groups; two groups received different doses of the alpha
      particle-labeled antibody (213)Bi-anti CD19 ((213)Bi-CD19), Thorotrast was
      administered to one group, and one group was left untreated. Hematoxylin and
      eosin-stained liver sections were evaluated for preneoplastic foci of altered
      hepatocytes 6, 12 and 17 months after treatment. The density and size
      distribution of focal transections were described by a mechanistic model for the
      formation and growth of foci of altered hepatocytes. The negative control and the
      (213)Bi-CD19 groups were combined to investigate the dose-response relationship
      for model parameters describing the formation and growth of foci of altered
      hepatocytes. Although (213)Bi-CD19 was given by single injection, the effect on
      formation of foci of altered hepatocytes lasted for the entire experiment.
      Likelihood-ratio tests comparing nested models showed that (213)Bi-CD19 increases
      the rates of both the formation and growth of foci of altered hepatocytes.
      Comparing the effects of Thorotrast with those of (213)Bi-CD19 revealed that
      Thorotrast had an effect similar to that of a low dose of (213)Bi-CD19, but the
      effect on focus formation was slightly smaller whereas the effect on focus growth
      was slightly higher for Thorotrast, in contrast to a low dose of (213)Bi-CD19.

PMID- 16881745
TI  - Implicit bicultural identity among Mexican American and Asian American college
      students.
AB  - Contemporary research on ethnic identity, acculturation, and cultural orientation
      suggests that, at least under some circumstances, individuals can successfully
      internalize or identify with more than one culture. Previous research on
      multicultural identity has relied almost exclusively on self-report measures.
      Using the Implicit Association Test (IAT), the present research examined to what
      extent Mexican American and Asian American college students identified with
      American culture and with their culture of origin. Results indicated that Mexican
      American and Asian American participants strongly and equally identified with
      both cultures. The present research provides firm evidence for a bicultural
      identity through assessments of thoughts that cannot be consciously controlled.
      Patterns of bicultural identification obtained on implicit measures were not the
      product of deliberate responses to normative demands or conscious attempts to
      convey a particular self-image.

PMID- 16881746
TI  - Factor structure of the Bulimia Test--Revised in college women from four ethnic
      groups.
AB  - The factor structure of the Bulimia Test--Revised (BULIT-R) was investigated
      using confirmatory factor analysis (CFA) and exploratory factor analysis (EFA).
      The sample consisted of 2,671 female college students (African American, Asian
      American, Caucasian American, and Latino American). Reliability coefficients were
      excellent across groups. African Americans scored significantly lower on the
      BULIT-R than Caucasian Americans. Across groups, CFA and EFA results suggest a
      six-factor solution is most appropriate. Consistent across groups were factors
      representing bingeing, body image, purging, and extreme weight loss behaviors,
      while few differences were observed across groups. These findings suggest that
      the measure is reliable and valid for use with diverse ethnic groups. Future
      research should focus on culturally salient psychological correlates of
      disordered eating in diverse ethnic groups.

PMID- 16881747
TI  - Sociocultural predictors of psychological help-seeking attitudes and behavior
      among Mexican American college students.
AB  - Sociocultural variables of acculturation, enculturation, cultural congruity, and
      perceived social support were used as predictors of psychological help-seeking
      attitudes and behaviors among 162 Mexican American college students. Multivariate
      multiple regression analyses indicated that higher cultural congruity, lower
      perceived social support from family, and higher perceived social support from
      significant others were significant predictors of positive help-seeking
      attitudes. In addition, higher acculturation into the dominant society, lower
      perceived social support from family, and lower perceived social support from
      friends were significantly predictive of greater help-seeking behavior.
      Implications for research and practice are discussed.

PMID- 16881748
TI  - Racism-related stress, Africultural coping, and religious problem-solving among
      African Americans.
AB  - This study explored the extent to which three types of racism-related stress
      (i.e., individual, institutional, and cultural) would predict the use of specific
      Africultural coping strategies (i.e., cognitive/emotional debriefing, spiritual
      centered, collective, and ritual-centered coping) and religious problem-solving
      styles (i.e., self-directing, deferring, and collaborative) in a sample of 284
      African American men and women. The authors found that higher institutional
      racism-related stress was associated with greater use of cognitive/emotional
      debriefing, spiritual-centered, and collective coping in African American women.
      Findings also indicated that higher cultural racism-related stress was predictive
      of lower use of self-directing religious problem-solving in African American
      women. Moreover, higher perceived cultural racism-related stress was related to
      greater use of collective coping strategies in African American men. Individual
      racism-related stress was not predictive of any forms of Africultural coping
      strategies or religious problem-solving. Implications of the findings are
      discussed.

PMID- 16881749
TI  - Challenging racism, sexism, and social injustice: support for urban adolescents'
      critical consciousness development.
AB  - This mixed-model study examined the relationship between urban adolescents'
      perceived support for challenging racism, sexism, and social injustice from
      peers, family, and community members and their critical consciousness
      development. These relationships were examined by relating participants'
      qualitative perceptions of support for challenging racism, sexism, and social
      injustice to quantitative data obtained from Likert-type measures of the
      reflection and action components of critical consciousness. Perceived support for
      challenging racism, sexism, and social injustice had a significant impact upon
      the reflection component of critical consciousness; the significance criterion
      was supported by effect size estimates. Support for challenging racism, sexism,
      and social injustice was not significantly related to the action component of
      critical consciousness. Participants perceived the most support for challenging
      racism, moderate support for challenging social injustice, and the least support
      for challenging sexism. Additionally, female participants perceived more support
      for challenging sexism than male participants. These results suggest that the
      informal interactions of urban adolescents play a role in shaping their critical
      consciousness, and hold implications for psychosocial interventions and research
      with marginalized populations.

PMID- 16881750
TI  - Exploring Asian American racial identity.
AB  - In this study the authors used cluster analysis to create racial identity
      profiles for a sample of Asian Americans using the People of Color Racial
      Identity Attitudes Scale (PCRIAS). A four-cluster solution was chosen: each
      cluster corresponded to one PCRIAS subscale and was named accordingly. Scores on
      the Asian American Racism-Related Stress Inventory and the Color-Blind Racial
      Attitudes Scale were compared across clusters. As expected, the Dissonance and
      Immersion clusters were characterized by relatively high racism-related stress
      and low levels of color-blind attitudes; the Conformity cluster showed roughly
      the opposite pattern. Surprisingly, the Internalization cluster showed a pattern
      similar to that for Conformity and thus may reflect "pseudoindependence" as
      discussed by Helms.

PMID- 16881751
TI  - Asian Americans and racism: when bad things happen to "model minorities.".
AB  - Due to the limited psychological research on Asian Americans' experiences with
      racism, in the current study the authors examined the relationships between
      racial socialization, racial identity, and perceptions of racism, with a college
      aged sample (N = 254) consisting primarily of Chinese Americans and Filipino
      Americans. With the use of multiple regression analyses, the results indicated
      that racial socialization, particularly discussions about race and racism, was
      positively related to one's perceptions of racism. Moreover, the study also
      showed that the relationship between racial socialization and perceptions of
      racism was partially mediated by racial identity schemas. To understand how Asian
      Americans regard racism, it is useful to have an understanding of racial identity
      theory and the manner in which Asian Americans are socialized to perceive racism.

PMID- 16881752
TI  - The psychology of engagement with indigenous identities: a cultural perspective.
AB  - In a questionnaire study among 124 students at Haskell Indian Nations University,
      the authors investigated the hypothesis that engagement with Indigenous identity-
      assessed along three dimensions including degree (identification scale), content
      (panethnic or tribal nation), and context (reservation or nonreservation)--can
      serve as a psychological resource for well-being and liberation from oppression.
      Consistent with this hypothesis, degree of identification was positively
      correlated with community efficacy and perception of racism. Apparently
      inconsistent with this hypothesis, degree of identification among students who
      had resided on a reservation was negatively correlated with the Social Self
      Esteem subscale of the Current Thoughts Scale. Rather than evidence against the
      identity-as-resource hypothesis, this pattern may reflect the cultural grounding
      of self-esteem and tools designed to measure it.

PMID- 16881754
TI  - On the risk of being a cultural chameleon: variations in collective self-esteem
      across social interactions.
AB  - In the present study the authors used an event-contingent daily recording
      strategy, the Rochester Interaction Record, to examine the relation of perceived
      evaluations of a multicultural person's heritage group to the nature and quality
      of his or her social interactions. Hierarchical linear modeling showed that
      having an interaction partner who positively evaluated one's heritage culture was
      associated with significantly enhanced interaction intimacy, disclosure, and
      quality, as well as with feelings of personal acceptance. Moderator analyses
      revealed that individuals who possessed a chameleon-like cultural identity and
      those who had low public collective self-esteem were particularly reactive to how
      their heritage group was being evaluated.

PMID- 16881753
TI  - On the importance of being ethnic: coping with the threat of prostate cancer in
      relation to prostate cancer screening.
AB  - The relation between coping with a possible prostate cancer diagnosis and
      screening behavior was examined in men from seven precise ethnic groups. Five
      coping styles differed in their likelihood of use across ethnic groups and had
      somewhat different associations with frequency of prostate-specific antigen (PSA)
      testing. As expected, PSA test frequency differed among men from different ethnic
      groups and was differentially predicted by coping styles. Analyzing the results
      using typical groups of White, Black, and Hispanic, rather than precise ethnic
      groups, obscured these results. Researchers investigating psychological variables
      in preventive health behaviors must analyze diversity within the framework
      provided by ethnic specificity. Such an approach will guide the development and
      provision of interventions that are more sensitive to the characteristics of
      specific ethnic groups of at risk men.

PMID- 16881755
TI  - Stress versus discrete negative emotions in the prediction of physical
      complaints: does predictive utility vary across ethnic groups?
AB  - Reports of stress and negative emotion are important predictors of health.
      However, whether discrete emotions or stress measures are more useful, whether
      they contribute independently to outcome, and whether they relate to health
      equally across ethnic groups remain unclear. In the current study, 207 US-born
      European American, US-born African American, Black English-speaking Caribbean,
      and Dominican men aged 40 years and older completed measures of somatic symptoms,
      trait emotions, and stress. Sadness and stress independently predicted symptom
      reports, even when examined concurrently, and with demographics controlled; trait
      anger did not predict symptoms. Moreover, the relations between trait emotions
      and symptoms varied across groups. Levels of sadness were associated with greater
      symptoms among US-born European American and Dominican men, but negatively
      associated among Black English-speaking Caribbean men, and the relations for
      anger also differed marginally across groups. The results underscore the
      importance of differentiating among discrete emotions and stress and considering
      ethnic interactions when examining reports of somatic symptomology. We suggest
      that the impact of psychological characteristics on health must be considered
      within cultural and ethnic contexts to be fully understood.

PMID- 16881756
TI  - When family enters the picture: the model of cultural negotiation and gendered
      experiences of Japanese academic sojourners in the United States.
AB  - A grounded-theory study aimed at reconceptualizing cultural adaptation processes
      from gender role and family/couple perspectives while critically drawing from
      acculturation and culture and self literatures. In-depth interviews with 34
      Japanese academic sojourners (international students, scholars) and their spouses
      (a total of 50 interviews with select longitudinal interviews) were conducted.
      The author earlier developed the Model of Cultural Negotiation (2001; 2006)
      capturing uneven and cyclical processes of dealing with multiple cultural
      contexts. The current study further develops more tailored versions of this
      model, Family-Based (Couple-Based) Cultural Negotiation and Individual-Based
      Cultural Negotiation, highlighting the impacts of family/couple and gender roles,
      especially for female spouses. These conceptualizations afford a sophisticated
      understanding of the processes of culture.

PMID- 16881757
TI  - Cognitions and depressive symptoms among ethnic minority adolescents.
AB  - Cognitive models have guided effective intervention strategies in the treatment
      of depression. However, little is known about the cognitive model's relevance in
      different cultural ethnic groups in the United States. This study examines the
      cross-sectional and longitudinal associations among cognitive variables and
      depressive symptoms among African American, Caucasian, and Hispanic adolescents
      in the United States. Community adolescents (N = 450) ages 14-18 years (African
      American n = 79; Caucasian n = 273; Hispanic n = 98) provided information
      regarding their depressive symptoms and cognitions at two surveys, 6 months
      apart. Self-efficacy, cognitive errors, and hopelessness were associated with
      concurrent depressive symptoms at baseline. In addition, cognitive errors at
      baseline, controlling for baseline depressive symptoms and the occurrence of
      stressful events, predicted depressive symptoms at follow-up. Ethnic differences
      disappeared when parent education level was controlled. Our findings demonstrate
      support for the cognitive model of depression across ethnic groups. The
      importance of controlling for social class when examining ethnic differences in
      psychological variables is highlighted by our findings.

PMID- 16881759
TI  - The role of task demands and processing resources in the use of base-rate and
      individuating information.
AB  - This article addresses the process that governs the use of base-rate and
      individuating information. Five experiments demonstrated that, for both,
      informational length and order of presentation (determining processing
      difficulty) interact with the recipients' processing resources to determine use.
      In cases in which the base-rate or the individuating information is brief and/or
      is presented early, the tendency to use it is greater under limited cognitive
      resources (cognitive load) than under ample cognitive resources. In contrast, in
      cases in which the base-rate or the individuating information is lengthy and/or
      is presented late in the informational sequence, the tendency to use it is
      greater under ample versus limited resources. These results suggest the
      appropriateness of conceptually decoupling informational contents (having to do
      with base rates or individuating descriptions) from the task demands (processing
      ease or difficulty) that a given judgmental problem presents and that may require
      different amounts of processing resources.

PMID- 16881760
TI  - Everyday magical powers: the role of apparent mental causation in the
      overestimation of personal influence.
AB  - These studies examined whether having thoughts related to an event before it
      occurs leads people to infer that they caused the event--even when such causation
      might otherwise seem magical. In Study 1, people perceived that they had harmed
      another person via a voodoo hex. These perceptions were more likely among those
      who had first been induced to harbor evil thoughts about their victim. In Study
      2, spectators of a peer's basketball-shooting performance were more likely to
      perceive that they had influenced his success if they had first generated
      positive visualizations consistent with that success. Observers privy to those
      spectators' visualizations made similar attributions about the spectators'
      influence. Finally, additional studies suggested that these results occur even
      when the thought-about outcome is viewed as unwanted by the thinker and even in
      field settings where the relevant outcome is occurring as part of a live athletic
      competition.

PMID- 16881761
TI  - Subgoals as substitutes or complements: the role of goal accessibility.
AB  - The self-regulation process often involves breaking an ongoing goal (e.g.,
      keeping in shape) into many individual, constituent subgoals that monitor actual
      actions (e.g., eating healthy meals, going to the gym). The article examines how
      pursuing each of these subgoals may influence subsequent goal pursuit. The
      authors show that when people consider success on a single subgoal, additional
      actions toward achieving a superordinate goal are seen as substitutes and are
      less likely to be pursued. In contrast, when people consider their commitment to
      a superordinate goal on the basis of initial success on a subgoal, additional
      actions toward achieving that goal may seem to be complementary and more likely
      to be pursued. These predictions were tested in four studies that explored the
      conditions under which subgoals attainment have a counterproductive versus
      favorable effect on further pursuit of similar actions.

PMID- 16881762
TI  - Distinguishing stereotype threat from priming effects: on the role of the social
      self and threat-based concerns.
AB  - It has been argued that priming negative stereotypic traits is sufficient to
      cause stereotype threat. The present research challenges this assumption by
      highlighting the role of the social self and targets' concerns about confirming a
      negative group-based stereotype. Specifically, in 3 experiments the authors
      demonstrate that stereotype threat adversely affects the test performance and
      threat-based concerns of targets (but not nontargets) because only targets'
      social self is linked to the negative group stereotype. Trait priming, however,
      harms the test performance of both targets and nontargets but has no effect on
      their threat-based concerns because trait priming does not require such a link
      between the social self and the group stereotype. Moreover, the authors show that
      merely increasing the accessibility of the social self in nonthreatening
      situations leads to the underperformance of targets but has no meaningful effect
      on nontargets' test performance.

PMID- 16881763
TI  - Does who you marry matter for your health? Influence of patients' and spouses'
      personality on their partners' psychological well-being following coronary artery
      bypass surgery.
AB  - Research suggests that presurgical personality attributes influence postsurgical
      well-being in both patients and their spouses in the context of coronary artery
      bypass grafting (CABG) surgery. The authors hypothesized that a spouse's
      characteristics would influence a partner's psychological well-being, regardless
      of whether he or she was the patient or the caregiver. In this study, 111 male
      patients and their caregiver spouses completed measures of neuroticism, optimism,
      perceived marital satisfaction, and depression prior to elective CABG. Follow-up
      was conducted at 18 months. As expected, higher caregiver presurgical neuroticism
      predicted higher patient depressive symptoms at follow-up, with caregiver's
      concurrent 18-month affect controlled for. Likewise, higher patient presurgical
      neuroticism predicted higher caregiver depressive symptoms at follow-up.
      Additionally, higher patient presurgical depressive symptoms and lower
      presurgical optimism contributed to greater caregiving burden. Relationship
      satisfaction moderated these effects. These results suggest that partners'
      personality traits are important determinants of both patients' and their
      caregiving spouses' well-being.

PMID- 16881764
TI  - From automatic antigay prejudice to behavior: the moderating role of conscious
      beliefs about gender and behavioral control.
AB  - Two experiments tested whether the relation between automatic prejudice and
      discriminatory behavior is moderated by 2 conscious processes: conscious
      egalitarian beliefs and behavioral control. The authors predicted that, when both
      conscious processes are deactivated, automatic prejudice would elicit
      discriminatory behavior. When either of the 2 processes is activated, behavioral
      bias would be eliminated. The authors assessed participants' automatic attitudes
      toward gay men, conscious beliefs about gender, behavioral control, and
      interactions with gay confederates. In Experiment 1, men's beliefs about gender
      were heterogeneous, whereas women's beliefs were mostly egalitarian; men's
      responses supported the predictions, but women's responses did not. In Experiment
      2, the authors recruited a sample with greater diversity in gender-related
      beliefs. Results showed that, for both sexes, automatic prejudice produced biased
      behavior in the absence of conscious egalitarian beliefs and behavioral control.
      The presence of either conscious process eliminated behavioral bias.

PMID- 16881765
TI  - Going along versus going alone: when fundamental motives facilitate strategic
      (non)conformity.
AB  - Three experiments examined how 2 fundamental social motives--self-protection and
      mate attraction--influenced conformity. A self-protective goal increased
      conformity for both men and women. In contrast, the effects of a romantic goal
      depended on sex, causing women to conform more to others' preferences while
      engendering nonconformity in men. Men motivated to attract a mate were
      particularly likely to nonconform when (a) nonconformity made them unique (but
      not merely a member of a small minority) and when (b) the topic was subjective
      versus objective, meaning that nonconformists could not be revealed to be
      incorrect. These findings fit with a functional evolutionary model of motivation
      and behavior, and they indicate that fundamental motives such as self-protection
      and mate attraction can stimulate specific forms of conformity or nonconformity
      for strategic self-presentation.

PMID- 16881766
TI  - Evidence for strong dissociation between emotion and facial displays: the case of
      surprise.
AB  - Eight experiments examined facial expressions of surprise in adults. Surprise was
      induced by disconfirming a previously established schema or expectancy. Self
      reports and behavioral measures indicated the presence of surprise in most
      participants, but surprise expressions were observed only in 4%-25%, and most
      displays consisted of eyebrow raising only; the full, 3-component display was
      never seen. Experimental variations of surprise intensity, sociality, and
      duration/complexity of the surprising event did not change these results.
      Electromyographic measurement failed to detect notably more brow raisings and, in
      one study, revealed a decrease of frontalis muscle activity in the majority of
      the participants. Nonetheless, most participants believed that they had shown a
      strong surprise expression.

PMID- 16881767
TI  - The evolutionary significance of depressive symptoms: different adverse
      situations lead to different depressive symptom patterns.
AB  - Although much depression may be dysfunctional, the capacity to experience normal
      depressive symptoms in response to certain adverse situations appears to have
      been shaped by natural selection. If this is true, then different kinds of
      situations may evoke different patterns of depressive symptoms that are well
      suited to solving the adaptive challenges specific to each situation. The authors
      called this the situation-symptom congruence hypothesis. They tested this
      hypothesis by asking 445 participants to identify depressive symptoms that
      followed a recent adverse situation. Guilt, rumination, fatigue, and pessimism
      were prominent following failed efforts; crying, sadness, and desire for social
      support were prominent following social losses. These significant differences
      were replicated in an experiment in which 113 students were randomly assigned to
      visualize a major failure or the death of a loved one.

PMID- 16881768
TI  - It's not just the amount that counts: balanced need satisfaction also affects
      well-being.
AB  - The basic psychological needs for autonomy, competence, and relatedness have been
      found to have unique additive effects on psychological well-being (see E. L. Deci
      & R. M. Ryan, 2000). In the present study, the authors extended these findings by
      examining whether the balance in the satisfaction of these 3 needs is also
      important. The results of 4 studies showed that people who experienced balanced
      need satisfaction reported higher well-being than those with the same sum score
      who reported greater variability in need satisfaction. This finding emerged for
      multiple measures of needs and adjustment and was independent of neuroticism.
      Moreover, results were obtained consistently across concurrent, prospective,
      daily diary, and observer-report study designs. Discussion focuses on the
      psychological meaning and functional implications of balanced need satisfaction.

PMID- 16881769
TI  - Expect the unexpected: ability, attitude, and responsiveness to hypnosis.
AB  - Participants' expectancies and hypnotic performance throughout the course of a
      standardized, individually administered hypnotic protocol were analyzed with a
      structural equation model that integrated underlying ability, expectancy, and
      hypnotic response. The model examined expectancies and ability as simultaneous
      predictors of hypnotic responses as well as hypnotic responses as an influence on
      subsequent expectancies. Results of the proposed model, which fit very well,
      supported each of the 4 major hypothesized effects: Expectancies showed
      significant stability across the course of the hypnosis protocol; expectancies
      influenced subsequent hypnotic responses, controlling for latent ability;
      hypnotic responses, in turn, affected subsequent expectancies; and a latent trait
      underlay hypnotic responses, controlling for expectancies. Although expectancies
      had a significant effect on hypnotic responsiveness, there was an abundance of
      variance in hypnotic performance unexplained by the direct or indirect influence
      of expectation and compatible with the presence of an underlying cognitive
      ability.

PMID- 16881770
TI  - Conceptual beliefs about human values and their implications: human nature
      beliefs predict value importance, value trade-offs, and responses to value-laden
      rhetoric.
AB  - Beliefs that may underlie the importance of human values were investigated in 4
      studies, drawing on research that distinguishes natural-kind (natural), nominal
      kind (conventional), and artifact (functional) beliefs. Values were best
      characterized by artifact and nominal-kind beliefs, as well as a natural-kind
      belief specific to the social domain, "human nature" (Studies 1 and 2). The
      extent to which values were considered central to human nature was associated
      with value importance in both Australia and Japan (Study 2), and experimentally
      manipulating human nature beliefs influenced value importance (Study 3). Beyond
      their association with importance, human nature beliefs predicted participants'
      reactions to value trade-offs (Study 1) and to value-laden rhetorical statements
      (Study 4). Human nature beliefs therefore play a central role in the psychology
      of values.

PMID- 16881771
TI  - A controlled social skills training for children with fetal alcohol spectrum
      disorders.
AB  - Children with fetal alcohol spectrum disorders (FASD) have significant social
      skills deficits. The efficacy of a child friendship training (CFT) versus a
      delayed treatment control (DTC) was assessed for 100 children ages 6 to 12 years
      with FASD. Children in the CFT showed clear evidence of improvement in their
      knowledge of appropriate social behavior, and according to parent report, CFT
      resulted in improved social skills and fewer problem behaviors compared with DTC.
      Gains were maintained at 3-month follow-up. After receiving treatment, the DTC
      group exhibited similar improvement. Teachers did not report improvement as a
      function of social skills treatment. The findings suggest that children with FASD
      benefit from CFT but that these social skills gains may not be observed in the
      classroom.

PMID- 16881772
TI  - Treatment-related changes in objectively measured parenting behaviors in the
      multimodal treatment study of children with attention-deficit/hyperactivity
      disorder.
AB  - The present study examined treatment outcomes for objectively measured parenting
      behavior in the Multimodal Treatment Study of Children with Attention
      Deficit/Hyperactivity Disorder (ADHD). Five hundred seventy-nine ethnically and
      socioeconomically diverse children with ADHD-combined type (ages 7.0-9.9 years)
      and their parent(s) were recruited at 6 sites in the United States and Canada and
      randomly assigned to 1 of 4 treatment groups for 14 months of active
      intervention: medication management (MedMgt), intensive behavior therapy,
      combination of the 2 (Comb), or a community-treated comparison (CC). Baseline and
      posttreatment laboratory observations of parent-child interactions were coded by
      observers blind to treatment condition. Comb produced significantly greater
      improvements in constructive parenting than did MedMgt or CC, with effect sizes
      approaching medium for these contrasts. Treatment effects on child behaviors were
      not significant. The authors discuss the importance of changes in parenting
      behavior for families of children with ADHD and the need for reliable and
      objective measures in evaluating treatment outcome.

PMID- 16881773
TI  - Randomized trial of behavioral activation, cognitive therapy, and antidepressant
      medication in the acute treatment of adults with major depression.
AB  - Antidepressant medication is considered the current standard for severe
      depression, and cognitive therapy is the most widely investigated psychosocial
      treatment for depression. However, not all patients want to take medication, and
      cognitive therapy has not demonstrated consistent efficacy across trials.
      Moreover, dismantling designs have suggested that behavioral components may
      account for the efficacy of cognitive therapy. The present study tested the
      efficacy of behavioral activation by comparing it with cognitive therapy and
      antidepressant medication in a randomized placebo-controlled design in adults
      with major depressive disorder (N = 241). In addition, it examined the importance
      of initial severity as a moderator of treatment outcome. Among more severely
      depressed patients, behavioral activation was comparable to antidepressant
      medication, and both significantly outperformed cognitive therapy. The
      implications of these findings for the evaluation of current treatment guidelines
      and dissemination are discussed.

PMID- 16881774
TI  - Patients' expectancies, the alliance in pharmacotherapy, and treatment outcomes
      in bipolar disorder.
AB  - Bipolar disorder is characterized by a chronic and fluctuating course of illness.
      Although nonadherence to pharmacotherapy is a frequent problem in the disorder,
      few studies have systematically explored psychosocial factors related to
      treatment discontinuation. Previous research with depressed patients receiving
      psychotherapy has suggested that expectancies for improvement are related to
      treatment outcomes and that the therapeutic alliance may partially mediate this
      relationship. The current study found evidence for a similar relationship between
      patients' initial expectancies for improvement, patient and doctor-rated
      alliance, and long-term outcomes in bipolar patients treated with pharmacotherapy
      for up to 28 months following an acute episode. The results highlight the need
      for the assessment of expectancies and alliance in bipolar treatment and suggest
      possible targets for psychosocial interventions.

PMID- 16881775
TI  - Internet-based self-help with therapist feedback and in vivo group exposure for
      social phobia: a randomized controlled trial.
AB  - Sixty-four individuals with social phobia (social anxiety disorder) were assigned
      to a multimodal cognitive-behavioral treatment package or to a waiting list
      control group. Treatment consisted of a 9-week, Internet-delivered, self-help
      program that was combined with 2 group exposure sessions in real life and minimal
      therapist contact via e-mail. Results were analyzed on an intention-to-treat
      basis, including all randomized participants. From pre- to posttest, treated
      participants in contrast to controls showed significant improvement on most
      measured dimensions (social anxiety scales, general anxiety and depression
      levels, quality of life). The overall within- and between-groups effect sizes
      were Cohen's d = 0.87 and 0.70, respectively. Treatment gains were maintained at
      1-year follow-up. The results from this study support the continued use and
      development of Internet-distributed, self-help programs for people diagnosed with
      social phobia.

PMID- 16881776
TI  - Sudden gains during therapy of social phobia.
AB  - The present study investigated the phenomenon of sudden gains in 107 participants
      with social phobia (social anxiety disorder) who received either cognitive
      behavioral group therapy or exposure group therapy without explicit cognitive
      interventions, which primarily used public speaking situations as exposure tasks.
      Twenty-two out of 967 session-to-session intervals met criteria for sudden gains,
      which most frequently occurred in Session 5. Individuals with sudden gains showed
      similar improvements in the 2 treatment groups. Although cognitive-behavioral
      therapy was associated with more cognitive changes than exposure therapy,
      cognitive changes did not precede sudden gains. In general, the results of this
      study question the clinical significance of sudden gains in social phobia
      treatment.

PMID- 16881777
TI  - Anger, hostility, and posttraumatic stress disorder in trauma-exposed adults: a
      meta-analysis.
AB  - This meta-analysis synthesizes the available data on the strength of association
      between anger and posttraumatic stress disorder (PTSD) and between hostility and
      PTSD, covering 39 studies with trauma-exposed adults. Effect sizes did not differ
      for anger and hostility, which could therefore be combined; effect sizes for
      anger expression variables were analyzed separately. The analyses revealed large
      effects. The weighted mean effect size (r) was .48 for anger-hostility, .29 for
      anger out, .53 for anger in, and -.44 for anger control. Moderator analyses were
      conducted for anger-hostility, showing that effect sizes were substantially
      larger with increasing time since the event and that effect sizes were larger in
      samples with military war experience than in samples that had experienced other
      types of traumatic events.

PMID- 16881778
TI  - Longitudinal analysis of the relationship between symptoms and quality of life in
      veterans treated for posttraumatic stress disorder.
AB  - This study examined how change in posttraumatic stress disorder (PTSD) symptoms
      relates to change in quality of life. The sample consisted of 325 male Vietnam
      veterans with chronic PTSD who participated in a randomized trial of group
      psychotherapy. Latent growth modeling was used to test for synchronous effects of
      PTSD symptom change on psychosocial and physical health-related quality of life
      within the same time period and lagged effects of initial PTSD symptom change on
      later change in quality of life. PTSD symptoms were associated with reduced
      quality of life before treatment. There were synchronous effects of symptom
      change on change in quality of life but no significant lagged effects. Results
      indicate the importance of measuring quality of life in future investigations of
      PTSD treatment.

PMID- 16881779
TI  - Passage meditation reduces perceived stress in health professionals: a
      randomized, controlled trial.
AB  - The authors evaluated an 8-week, 2-hr per week training for physicians, nurses,
      chaplains, and other health professionals using nonsectarian, spiritually based
      self-management tools based on passage meditation (E. Easwaran, 1978/1991).
      Participants were randomized to intervention (n = 27) or waiting list (n = 31).
      Pretest, posttest, and 8- and 19-week follow-up data were gathered on 8 measures,
      including perceived stress, burnout, mental health, and psychological well-being.
      Aggregated across examinations, beneficial treatment effects were observed on
      stress (p = .0013) and mental health (p = .03). Treatment effects on stress were
      mediated by adherence to practices (p = .05). Stress reductions remained large at
      19 weeks (84% of the pretest standard deviation, p = .006). Evidence suggests
      this program reduces stress and may enhance mental health.

PMID- 16881780
TI  - Childhood sexual abuse and sexual risk behavior among men and women attending a
      sexually transmitted disease clinic.
AB  - Childhood sexual abuse (CSA) is associated with a wide range of negative
      outcomes. The authors investigated the relation between CSA and sexual risk
      behavior in 827 patients recruited from a sexually transmitted disease (STD)
      clinic. Overall, CSA was reported by 53% of women and 49% of men and was
      associated with greater sexual risk behavior, including more sexual partners,
      unprotected sex, and sex trading. Alcohol use for men and drug use for women
      mediated the relation between CSA and the number of sexual partners in the past 3
      months; intimate partner violence mediated the relation between CSA and the
      number of episodes of unprotected sex in the past 3 months for women. These
      results document the prevalence of CSA among patients seeking care for an STD and
      can be used to tailor sexual risk reduction programs for individuals who were
      sexually abused.

PMID- 16881782
TI  - Substance use and community violence: a test of the relation at the daily level.
AB  - Prior research has consistently demonstrated an association between substance use
      and involvement in violence among individuals with mental illness. Yet little is
      known about the temporal quality of this relationship, largely because
      longitudinal data required to address this issue are not readily available. This
      study examined the relationship between substance use (alcohol, marijuana, and
      other drug use) and violence at the daily level within a sample of mentally ill
      individuals at high risk for frequent involvement in violence (N = 132). Results
      support the serial nature of substance use and violence, with an increased
      likelihood of violence on days following the use of alcohol or multiple drugs,
      but not the inverse relationship. Implications for the utility of substance use
      as a risk marker for the assessment of future violence are discussed.

PMID- 16881781
TI  - Initiation, desistance, and persistence of men's sexual coercion.
AB  - Patterns of sexually coercive behavior were examined among 266 Asian American and
      299 European American men over 1 year. Noncoercer (n = 358), desister (n = 120),
      initiator (n = 39), and persistent (n = 48) sexually coercive groups were
      identified. The strongest predictor of sexual coercion was past sexual coercion.
      Persistent sexual coercers were higher than the other groups in delinquency and
      hostile masculinity and were nearly twice as likely to engage in laboratory
      sexual harassment. Loss of face attenuated self-reported sexual coercion and
      laboratory sexual harassment risk among Asian Americans and attenuated only
      laboratory sexual harassment risk among European Americans. These findings
      suggest that the heterogeneity of sexually coercive behavior and ethnicity are
      important research and clinical considerations.

PMID- 16881783
TI  - A cross-cultural analysis of the demand-withdraw marital interaction: observing
      couples from a developing country.
AB  - The authors used cross-cultural methodology to examine the demand-withdraw
      pattern of marital communication. In Western countries, women usually make more
      demands, whereas men are more likely to withdraw. But the recently advanced
      marital structure hypothesis suggests that this pattern can be altered by gender
      roles and beliefs, particularly in traditional marriages. To test such
      hypotheses, the authors conducted an observational study of marital communication
      across very different cultures, with varying levels of patriarchy (i.e., 50 White
      American couples, 52 Pakistani couples in Pakistan, and 48 immigrant Pakistani
      couples in America). Across cultures, demand-withdraw communication was related
      to marital distress, extending previous findings to new groups. However, the
      findings challenge the notion that demanding and withdrawing behaviors are
      inherently male or female; rather, the results point to the relevance of
      contextual factors, specifically gender power differences and acculturation, in
      understanding the demand-withdraw marital interaction pattern. Therapists working
      with foreign or immigrant couples must consider the cross-cultural
      generalizability of existing theories of marital communication.

PMID- 16881784
TI  - Altering misperception of sleep in insomnia: behavioral experiment versus verbal
      feedback.
AB  - Forty-eight individuals with insomnia were asked to wear an actigraph and keep a
      sleep diary for 2 nights. On the following day, half were shown the discrepancy
      between the data recorded on the actigraph and their sleep diary via a behavioral
      experiment, whereas the other half were told of the discrepancy verbally.
      Participants were then asked to monitor their sleep for 2 further nights to index
      the effect of these interventions. Although both reduced sleep misperception, the
      behavioral experiment (effect size: 0.79 to 1.25) led to greater reduction in
      self-reported sleep impairment, insomnia symptoms, and sleep-related anxiety and
      distress compared with verbal feedback (effect size: -0.06 to 0.31). Further, the
      patients regarded the behavioral experiment as a more beneficial and acceptable
      intervention strategy than verbal feedback.

PMID- 16881785
TI  - Recruitment and selection of couples for intervention research: achieving
      developmental homogeneity at the cost of demographic diversity.
AB  - Demographic and relationship quality data were collected from 704 individuals
      recruited to participate in a randomized study of relationship enhancing
      interventions. Recruiting at bridal shows produced partners who were more
      satisfied, earlier in their relationships, and less likely to be parents, with a
      marginally higher proportion of Latino couples. Radio and television coverage
      produced more established couples with higher levels of relationship discord.
      Self-selection effects revealed that couples from demographic groups at greater
      risk for divorce (those who had not completed high school, those with children at
      marriage, and African American couples) were more likely to agree to participate.
      In contrast, imposing a set of common selection criteria served to exclude
      couples from demographic risk groups and selected for couples with higher marital
      quality. Implications for recruiting couples to participate in preventive
      interventions are outlined.

PMID- 16881786
TI  - Social ecological model of illness management in high-risk youths with type 1
      diabetes.
AB  - In this study, the authors tested a social ecological model of illness management
      in high-risk, urban adolescents with Type 1 diabetes. It was hypothesized that
      management behaviors would be associated with individual adolescent
      characteristics as well as family, peer, and provider relationships.
      Questionnaires were collected from 96 adolescents in poor metabolic control and
      their primary caregivers. Variables in each system were correlated with illness
      management. Multiple regression demonstrated that higher externalizing symptoms,
      poorer family relationships, lower satisfaction with providers, and greater age
      contributed to the variance in illness management. Internalizing symptoms and
      peer relationships were no longer significant in the model. Results support a
      social ecological model of illness management in high-risk youths. Interventions
      grounded in social ecological theory are discussed.

PMID- 16881787
TI  - Identification of 3D shape from texture and motion across the visual field.
AB  - Little is known about the perception of 3D shape in the visual periphery. Here we
      ask whether identification accuracy in shape-from-texture and shape-from-motion
      tasks can be equated across the visual field with sufficient stimulus
      magnification. Both tasks employed 3D surfaces comprising hills, valleys, and
      plains in three possible locations, yielding a 27 alternative forced-choice task
      (27AFC). Participants performed the task at eccentricities of 0 to 16 deg in the
      right visual field over a 64-fold range of stimulus sizes. Performance reached
      ceiling levels at all eccentricities, indicating that stimulus magnification was
      sufficient to compensate for eccentricity-dependent sensitivity loss. The
      parameter E(2) (in the equation F = 1 + E / E(2)) was used to characterize the
      rate at which stimulus size must increase with eccentricity (E) to achieve foveal
      levels of performance. Three parameter models (mu, sigma, and E(2)) captured most
      of the variability in the psychometric functions relating stimulus size and
      eccentricity to accuracy for all participants' data in the two experiments. For
      the shape-from-texture task, the average E(2) was 1.52, and for the shape-from
      motion task, it was 0.61. The E(2) values indicate that sensitivity to structure
      from motion declines at a faster rate with eccentricity than does sensitivity to
      structure from texture. Although size scaling with F = 1 + E / E(2) eliminated
      most eccentricity variation from the structure-from-motion data, there was some
      evidence that E(2) increases as accuracy decreases in the shape-from-texture
      task, suggesting that there may be more than one eccentricity-dependent
      limitation on performance in this task.

PMID- 16881788
TI  - Vision and touch are automatically integrated for the perception of sequences of
      events.
AB  - The purpose of the present experiment was to investigate the integration of
      sequences of visual and tactile events. Subjects were presented with sequences of
      visual flashes and tactile taps simultaneously and instructed to count either the
      flashes (Session 1) or the taps (Session 2). The number of flashes could differ
      from the number of taps by +/-1. For both sessions, the perceived number of
      events was significantly influenced by the number of events presented in the task
      irrelevant modality. Touch had a stronger influence on vision than vision on
      touch. Interestingly, touch was the more reliable of the two modalities-less
      variable estimates when presented alone. For both sessions, the perceptual
      estimates were less variable when stimuli were presented in both modalities than
      when the task-relevant modality was presented alone. These results indicate that
      even when one signal is explicitly task irrelevant, sensory information tends to
      be automatically integrated across modalities. They also suggest that the
      relative weight of each sensory channel in the integration process depends on its
      relative reliability. The results are described using a Bayesian probabilistic
      model for multimodal integration that accounts for the coupling between the
      sensory estimates.

PMID- 16881789
TI  - High-speed navigators: Using more than what meets the eye.
AB  - This study employed a novel method to dissociate the use of external visual
      information and internal spatial representations in human navigation. Using a
      goal-directed walking task and gaze-contingent displays, 14 participants with
      normal vision navigated within an immersive virtual forest during which each
      participant's field of view (FOV) was restricted to 10, 20, or 40 deg in
      diameter. Participants were classified into two groups, good and poor navigators,
      based on a cluster analysis of their individual mean latencies, walk times, and
      path efficiencies in the 10 deg condition. Changes in performance measures across
      the three FOVs were calculated for the two groups. Significant interactions were
      found, with the overall performance of the poor navigators decreasing at a faster
      rate than the performance of the good navigators. Perceptual spans were also
      calculated for the two groups, and it was determined that the good navigators
      were able to complete the same task as effectively as the poor navigators with a
      smaller FOV. Collectively, these results support recent theories stating that
      good navigators rely on internal spatial representations to a greater extent than
      poor navigators do.

PMID- 16881791
TI  - The role of spatial phase in texture segmentation and contour integration.
AB  - It has been recently argued that the visual system possesses just two phase
      "detector" mechanisms, namely, +cosine and -cosine (P. C. Huang, F. A. Kingdom, &
      R. F. Hess, 2006). This suggests rather limited access to the rich distribution
      of receptive field phase that neurophysiologists tell us are represented in the
      different response profiles of striate simple cells. Whereas that study has
      suggested that striate receptive field phase is not directly available to
      perception for the detection/discrimination of localized stimuli, here we
      investigate whether such information might be used in more integrative striate or
      extrastriate functions such as texture segregation or contour integration.
      Specifically, given that simple cells have different local absolute phase
      response profiles, we ask whether a network of simple cells with similar phase
      preferences interact in such a way as to extract textures, contours, or both
      based on phase alone. Two novel texture segmentation experiments and one contour
      integration experiment were carried out with the intention of providing an answer
      to the question of how useful is local absolute spatial phase for texture
      segmentation and contour integration. The results support the possibility of two
      phase mechanisms (+/-cosine) for global texture segmentation, as well as for
      contour integration, when the elements that make up a given contour are
      orthogonal to contour paths.

PMID- 16881790
TI  - Contrast-response functions for multifocal visual evoked potentials: a test of a
      model relating V1 activity to multifocal visual evoked potentials activity.
AB  - The multifocal visual evoked potential (mfVEP) is largely generated in V1. To
      relate the electrical activity recorded from humans to recordings from single
      cells in nonhuman primate (V1) cortex, contrast-response functions for the human
      mfVEP were compared to predictions from a model of V1 activity (D. J. Heeger, A.
      C. Huk, W. S. Geisler, & D. G. Albrecht, 2000) based upon single-cell recordings
      from monkey V1 (e.g., D. G. Albrecht, 1995; D. G. Albrecht, W. S. Geisler, R. A.
      Frazor, & A. M. Crane, 2002; D. G. Albrecht & D. B. Hamilton, 1982; W. S. Geisler
      & D. G. Albrecht, 1997). A second purpose was to fully articulate the assumptions
      of this model to better understand the implications of this comparison. Finally,
      as the third purpose, one of these assumptions was tested. Monocular mfVEPs were
      obtained from normal subjects with a contrast-reversing dartboard pattern. The
      display contained 16 sectors each with a checkerboard. Both the sectors and the
      checks were scaled approximately for cortical magnification. In Experiment 1,
      there were 64 checks per sector. The contrast-response functions were fitted well
      up to 40% contrast by the theoretical population curve for V1 neurons; there was
      a systematic deviation for higher contrasts. The model, as articulated here,
      predicts that the contrast-response function should be the same and independent
      of the size of the elements in the display. Varying the size of the elements by
      varying the viewing distance in Experiment 2 produced similar results to those in
      Experiment 1. In Experiment 3, the viewing distance and sector size were held
      constant, but the size of the elements (and therefore the number of checks per
      sector) was varied. Changing check size by a factor of 16 had relatively little
      effect on the contrast-response function. In general, the mfVEP results were
      consistent with the model based upon the V1 neuron population. However, two
      aspects of the results require further exploration. First, there was a systematic
      deviation from the model's contrast-response function for higher contrasts. This
      deviation suggests that one or more of the model's assumptions may be violated.
      Second, the latency of the mfVEP changed far less than expected based upon single
      cell data.

PMID- 16881792
TI  - Stability of gold bead tissue markers.
AB  - Significant soft tissue features in the orbit and elsewhere are not resolved by
      MRI or any other imaging method. We describe a new method that uses tiny (
      approximately 0.1 mm diameter) gold beads as markers to visualize movements of
      such tissues with high spatial resolution ( approximately 100 microm) and
      moderate temporal resolution ( approximately 100 ms). We describe bead
      fabrication, implantation, imaging, and image processing to extract three
      dimensional bead coordinates. We then present results of an experiment to
      determine the stability of gold bead tissue markers (GBTMs) over time in normally
      moving orbital tissues. Most beads (76%) implanted in sclera, muscle, tendon, and
      connective tissue were highly stable over the 6-month measurement period. Beads
      that were judged unstable drifted only a few 100 microm. Bead flows with gaze
      suggested that posterior Tenon's capsule moves with the globe, that the lateral
      rectus belly may sideslip, producing "bridle forces," and that the posterior
      medial rectus pulley sling moves freely anteriorly and posteriorly, but hardly
      vertically, as required by the "coordinated active pulley" hypothesis. The GBTM
      method seems applicable to study such short time course phenomena as extraocular
      muscle (EOM) and connective tissue movement as a function of gaze and such long
      time course phenomena as myopic eye growth.

PMID- 16881793
TI  - Illusory spreading of watercolor.
AB  - The watercolor effect (WCE) is a phenomenon of long-range color assimilation
      occurring when a dark chromatic contour delineating a figure is flanked on the
      inside by a brighter chromatic contour; the brighter color spreads into the
      entire enclosed area. Here, we determined the optimal chromatic parameters and
      the cone signals supporting the WCE. To that end, we quantified the effect of
      color assimilation using hue cancellation as a function of hue, colorimetric
      purity, and cone modulation of inducing contours. When the inner and outer
      contours had chromaticities that were in opposite directions in color space, a
      stronger WCE was obtained as compared with other color directions. Additionally,
      equal colorimetric purity between the outer and inner contours was necessary to
      obtain a large effect compared with conditions in which the contours differed in
      colorimetric purity. However, there was no further increase in the magnitude of
      the effect when the colorimetric purity increased beyond a value corresponding to
      an equal vector length between the inner and outer contours. Finally, L-M-cone
      modulated WCE was perceptually stronger than S-cone-modulated WCE for our
      conditions. This last result demonstrates that both L-M-cone and S-cone pathways
      are important for watercolor spreading. Our data suggest that the WCE depends
      critically upon the particular spatiochromatic arrangement in the display, with
      the relative chromatic contrast between the inducing contours being particularly
      important.

PMID- 16881794
TI  - How direction of illumination affects visually perceived surface roughness.
AB  - We examined visual estimation of surface roughness using random, computer
      generated, three-dimensional (3D) surfaces rendered under a mixture of diffuse
      lighting and a punctate source. The angle between the tangent to the plane
      containing the surface texture and the direction to the punctate source was
      varied from 50 to 70 deg across lighting conditions. Observers were presented
      with pairs of surfaces under different lighting conditions and indicated which 3D
      surface appeared rougher. Surfaces were viewed either in isolation or in scenes
      with added objects whose shading, cast shadows, and specular highlights provided
      information about the spatial distribution of illumination. All observers
      perceived surfaces to be markedly rougher with decreasing illuminant angle.
      Performance in scenes with added objects was no closer to constant than that in
      scenes without added objects. We identified four novel cues that are valid cues
      to roughness under any single lighting condition but that are not invariant under
      changes in lighting condition. We modeled observers' deviations from roughness
      constancy as a weighted linear combination of these "pseudocues" and found that
      they account for a substantial amount of observers' systematic deviations from
      roughness constancy with changes in lighting condition.

PMID- 16881795
TI  - Motion from occlusion.
AB  - Vision uses specific image features or cues to infer physical properties of the
      world. Here, we use a novel illusion to show that occlusion, traditionally
      thought of as a cue to depth, is also a powerful cue to motion. A display of
      stacking disks that contains only occlusion as a cue to depth generates a vivid
      sense of movement that is likely computed in early or middle levels of visual
      processing.

PMID- 16881796
TI  - Accommodative microfluctuations and iris contour.
AB  - Mechanical interaction between aqueous humor, iris, and intraocular structures
      can alter the iris profile from its normal curvature. In particular, significant
      changes to the iris profile occur during accommodation as the anterior lens
      movement forces the iris into greater posterior bowing. We extended a previous
      mathematical model of the anterior segment and investigated the response of this
      coupled fluid-solid system due to accommodative microfluctuations. The results
      showed that the system response exhibited the same waveform as the stimulus for
      small-amplitude microfluctuations generally associated with the high-frequency
      component. Low-frequency microfluctuations with relatively larger amplitudes
      elicited a response different from the stimulus, indicating that the forces
      generated by the lens movement significantly affected the aqueous-iris mechanical
      interaction.

PMID- 16881797
TI  - Hastening orientation sensitivity.
AB  - Previous perceptual learning studies have shown that sensitivity to subtle
      orientation differences improves with practice at oblique axes but not with
      practice at cardinal axes. The cause of this anisotropy in angular resolution is
      uncertain, and it is not known whether the same anisotropy pertains to temporal
      resolution-the minimum stimulus duration needed to achieve a specified angular
      resolution. Here, we investigated the hypothesis that cardinal improvements were
      previously absent because long stimulus durations yielded maximal precision, even
      at the start of training. Accordingly, we exploited the relatively imprecise
      responses that occur naturally when masked stimuli are presented for extremely
      brief durations. After 110,000 trials were completed over seven daily sessions,
      temporal resolution improved by 51% at cardinal axes and by 86% at oblique axes.
      This hastening of the visual response was accompanied by significant improvements
      in angular resolution, which were specific to the trained axis. The data
      demonstrate plasticity in the response to cardinal orientations and indicate that
      sufficient initial levels of neural imprecision may be necessary for perceptual
      learning.

PMID- 16881798
TI  - Diabetes mellitus and periodontal diseases.
AB  - BACKGROUND: The purpose of this review is to provide the reader with practical
      knowledge concerning the relationship between diabetes mellitus and periodontal
      diseases. Over 200 articles have been published in the English literature over
      the past 50 years examining the relationship between these two chronic diseases.
      Data interpretation is often confounded by varying definitions of diabetes and
      periodontitis and different clinical criteria applied to prevalence, extent, and
      severity of periodontal diseases, levels of glycemic control, and complications
      associated with diabetes. METHODS: This article provides a broad overview of the
      predominant findings from research published in English over the past 20 years,
      with reference to certain "classic" articles published prior to that time.
      RESULTS: This article describes current diagnostic and classification criteria
      for diabetes and answers the following questions: 1) Does diabetes affect the
      risk of periodontitis, and does the level of metabolic control of diabetes have
      an impact on this relationship? 2) Do periodontal diseases affect the
      pathophysiology of diabetes mellitus or the metabolic control of diabetes? 3)
      What are the mechanisms by which these two diseases interrelate? and 4) How do
      people with diabetes and periodontal disease respond to periodontal treatment?
      CONCLUSIONS: Diabetes increases the risk of periodontal diseases, and
      biologically plausible mechanisms have been demonstrated in abundance. Less clear
      is the impact of periodontal diseases on glycemic control of diabetes and the
      mechanisms through which this occurs. Inflammatory periodontal diseases may
      increase insulin resistance in a way similar to obesity, thereby aggravating
      glycemic control. Further research is needed to clarify this aspect of the
      relationship between periodontal diseases and diabetes.

PMID- 16881799
TI  - Anti-neutrophil cytoplasmic autoantibodies: a renewed paradigm in periodontal
      disease pathogenesis?
AB  - In the past, various models including the autoimmunity model have been proposed
      to explain the pathogenesis of periodontal diseases. The aim of this review is to
      introduce the pathogenic role of anti-neutrophil cytoplasmic autoantibodies
      (ANCAs) in various autoimmune diseases and compare these conditions with
      periodontal disease to elucidate common pathogenic mechanisms. Also, a novel
      model to explain the pathogenesis of periodontal disease based on the concept of
      ANCA-associated autoimmunity is proposed. This encompasses a wide array of
      biochemical mediators that range from direct and indirect initiators of ANCA
      production and eventual release of proinflammatory mediators and free radicals,
      all of which have been implicated in periodontal tissue destruction in the past.
      In addition, specific links between the typical ANCA-associated diseases and
      periodontal disease are discussed. Finally, a new paradigm in the periodontal
      disease-associated destruction is proposed that includes the currently accepted
      mechanism, namely, the genetic-microbial-host interactions.

PMID- 16881800
TI  - New composite endpoints to assess efficacy in periodontal therapy clinical
      trials.
AB  - BACKGROUND: Clinical attachment level (CAL) and bone height (radiographic or
      clinical) are two well-accepted endpoint measures for periodontal clinical
      trials; however, neither one has been shown to be more predictive of long-term
      success than the other. We propose using a composite endpoint analysis combining
      clinical and radiological parameters to assess the beneficial effects on both
      hard and soft tissues following periodontal therapy using a single statistical
      test. To address this need, two composite endpoint alternatives are offered as a
      yardstick for clinical success; each includes the improvement in CAL and either
      improvement in linear bone growth or percent bone fill. METHODS: The data for
      composite endpoint analyses were derived from a clinical trial evaluating two
      concentrations of recombinant human platelet-derived growth factor-BB (rhPDGF-BB)
      with beta-tricalcium phosphate (beta-TCP) compared to beta-TCP plus buffer as
      follows: group I, beta-TCP + 0.3 mg/ml rhPDGF-BB; group II, beta-TCP + 1.0 mg/ml
      rhPDGF-BB; and group III, beta-TCP + buffer. The construction of composite
      endpoints was based on the greatest values for change, accepted by the U.S. Food
      and Drug Administration (FDA), for clinical attachment level (DeltaCAL), mean
      change in radiographic linear bone gain (LBG), and mean radiographic percent bone
      fill (%BF), with the following dual standards defining a successful clinical
      result: CAL gain > or =2.67 mm and radiographic LBG > or =1.1 mm at 6 months and
      CAL gain > or =2.67 mm and radiographic %BF > or =14.1% at 6 months. RESULTS:
      Group I (beta-TCP + 0.3 mg/ml rhPDGF-BB) demonstrated statistically significant
      differences from group III (active control) for both composite endpoints. For the
      CAL/LBG composite endpoint, 61.7% of sites in group I versus 30.4% of sites in
      group III met the composite endpoint benchmarks (P <0.001). For the CAL/%BF
      composite endpoint, 70% of sites in group I versus 44.6% of sites in group III
      met the composite endpoint benchmarks (P = 0.003). A non-significant trend was
      observed for group II versus group III with 37.9% (P = 0.20) and 55.2% (P = 0.13)
      of sites meeting the CAL/LBG and CAL/%BF composite endpoints, respectively. These
      results are further emphasized by findings demonstrating a low correlation
      between the individual efficacy endpoints (DeltaCAL and %BF; DeltaCAL and LBG)
      for each of the three treatment groups. CONCLUSIONS: Composite endpoints are
      advantageous in periodontal clinical trials where no single efficacy endpoint has
      been established as the most important. A composite endpoint, combining outcome
      measures of both hard and soft tissue components of the periodontium, may be
      preferable for assessing efficacy of periodontal regenerative therapies. Two
      composite endpoints are offered to meet this need.

PMID- 16881801
TI  - Sampling strategy for intraoral detection of periodontal pathogens before and
      following periodontal therapy.
AB  - BACKGROUND: The aim of this study was to identify a sampling strategy with high
      probability for detecting oral colonization by Actinobacillus
      actinomycetemcomitans, Porphyromonas gingivalis, Eikenella corrodens, Tannerella
      forsythensis, Prevotella intermedia, Prevotella nigrescens, and Treponema
      denticola before and following mechanical periodontal therapy. METHODS: Samples
      were taken from the following intraoral sites in 35 patients with untreated
      chronic periodontitis before and 1.5, 3, and 6 months after non-surgical
      periodontal therapy: supra- and subgingival plaque from the deepest pockets in
      each sextant; pooled supra- and subgingival plaque from another six randomly
      selected, less affected teeth; mucosal swab samples from the tongue, tonsils,
      throat, and buccal mucosa; and stimulated and unstimulated saliva. Microbial
      species were identified by polymerase chain reaction (PCR). RESULTS: Of the
      sampling of all assessed sites, the highest probability for simultaneously
      detecting the tested pathogens was found in respect to the combination of supra-
      and subgingival plaque samples taken from the most affected tooth in each sextant
      in untreated patients (probability: 83% to 95% for the assessed bacteria). These
      results were consistently observed throughout the study period. CONCLUSIONS: For
      determining the intraoral carrier state of patients with periodontitis, a
      combined sample of supra- and subgingival plaque taken from the deepest
      periodontal pocket in each sextant may yield the most reliable result. This
      sampling strategy may be used in routine microbial testing and clinical research.

PMID- 16881802
TI  - Risk of Porphyromonas gingivalis recolonization during the early period of
      periodontal maintenance in initially severe periodontitis sites.
AB  - BACKGROUND: Porphyromonas gingivalis is considered a critical pathogen of
      periodontal diseases including recurrent periodontitis. The profound effects of
      active periodontal treatment (APT) on P. gingivalis elimination were previously
      demonstrated and revealed that the subsequent P. gingivalis-free or -suppressed
      status seems to be maintained during early periodontal maintenance (PMT). The aim
      of the present study was to show the occurrence of microbial recolonization
      during this early PMT period. METHODS: In total, 128 sites from 11 generalized
      chronic periodontitis patients and one generalized aggressive periodontitis
      patient underwent clinical and microbiologic examination at baseline (Exam-I),
      after APT (Exam-II), and in PMT (Exam-III). Exam-III was carried out an average
      of 4.5 +/- 3.5 months after Exam-II. Detection and quantification of putative
      pathogens were performed using a polymerase chain reaction-based method. RESULTS:
      The PMT used was effective in maintaining the clinical conditions improved by
      APT. However, in microbiological examinations, Exam-III showed higher detection
      frequency and levels of P. gingivalis than Exam-II. This suggests that a P.
      gingivalis recolonization started in the early PMT period. P. gingivalis
      increased sites then showed significantly more severe signs of periodontitis in
      Exam-I than P. gingivalis-stable sites (bleeding on probing frequency: 76.7%
      versus 56.5%; suppuration frequency: 41.9% versus 12.9%). On the other hand, in
      Exam-II, no significant differences of clinical parameters were noted between P.
      gingivalis-increased and -stable sites. CONCLUSION: Severe periodontitis sites
      before APT seemed to place them at risk of P. gingivalis recolonization in the
      early PMT period, and this microbial restoration could be a cause of recurrent
      periodontitis.

PMID- 16881803
TI  - Endothelial nitric oxide synthase Glu298Asp gene polymorphism in periodontal
      diseases.
AB  - BACKGROUND: Endothelial nitric oxide synthase (eNOS) is involved in key steps of
      immune response. The aim of the present study was to evaluate genotype
      distribution and genotype-phenotype association in periodontal disease regarding
      Glu298Asp polymorphism of the eNOS gene. METHODS: A total of 272 subjects were
      included into the study. Genomic DNA was obtained from the peripheral blood of 51
      chronic periodontitis (CP) patients, 48 generalized aggressive periodontitis
      (GAgP), and 173 reference controls. Polymerase chain reaction (PCR) amplification
      and subsequent BanII restriction fragment length polymorphism (RFLP) analysis
      were used to detect eNOS Glu298Asp polymorphism. Probing depth, clinical
      attachment loss, plaque accumulation, and bleeding on probing (BOP) were
      recorded. The data were analyzed by the chi2 test, logistic regression, and Mann
      Whitney U test. RESULTS: The distributions of eNOS Glu298Asp genotypes and
      alleles were similar among study groups. Subjects with the Asp allele (Asp+) were
      statistically higher in the CP group compared to the control group (odds ratio
      [OR] = 1.957; 95% confidence interval [95% CI] = 1.038 to 3.689). In the GAgP
      group, BOP (%) was significantly higher in patients with the 298Asp allele (Asp+)
      compared to patients without the Asp allele (Asp-) (P = 0.015). CONCLUSIONS: The
      present study showed that eNOS Glu298Asp polymorphism is associated with BOP in
      GAgP patients. Moreover, the 298Asp allele of the eNOS gene might be related to
      CP in the Turkish population.

PMID- 16881804
TI  - The induction and possible subsequent effect of human antibodies against porcine
      enamel matrix derivative.
AB  - BACKGROUND: The amino acid sequence of porcine amelogenin, the major component of
      enamel matrix derivative (EMD), is approximately 91% identical to that of its
      human counterpart. Whether porcine EMD (pEMD) can elicit neutralizing antibodies
      after the first surgery, thereby reducing the clinical effect of secondary
      surgery, has not been established. METHODS: The sera of patients receiving
      periodontal surgery with or without pEMD were collected before and after surgery.
      The pEMD product was subjected to electrophoresis and transferred for a Western
      blot using the purified antibodies from patients as the primary antibodies. To
      clarify whether the antibodies in patients could inhibit the production of
      transforming growth factor-beta1 (TGF-beta1), we added different amounts of
      purified antibodies from pEMD patients (before versus after surgery) into the
      cell cultures of periodontal ligament fibroblasts. The conditioned media were
      then collected for an immunoassay of TGF-beta1. RESULTS: The result of the
      Western blot demonstrated that human antibodies against pEMD were elicited 10
      days after surgery. Using mass spectrometry, a non-specific band on the Western
      blot appeared to be porcine immunoglobulin G (IgG). The results of the
      immunoassay showed the antibodies from pEMD-treated patients did not hinder the
      subsequent production of TGF-beta1. CONCLUSIONS: The pEMD product was
      contaminated with porcine IgG. The application of the product could induce
      antibodies against different isoforms of porcine amelogenin in humans. However,
      the increased antibodies did not hinder the production of TGF-beta1, one of the
      established in vitro functions of pEMD on periodontal ligament fibroblasts.

PMID- 16881805
TI  - Prostanoid- and interleukin-1-induced primary genes in cementoblastic cells.
AB  - BACKGROUND: Cementum is a key component of a functional periodontal organ.
      However, regenerating lost cementum is difficult and often incomplete.
      Identifying molecular mediators of cementoblast differentiation and function
      should lead to better targeted treatment for periodontitis. Prostaglandins
      increase mineralization of murine cementoblastic OCCM cells and alveolar bone
      formation, whereas the cytokine interleukin-1 (IL-1) inhibits alveolar bone
      formation. We hypothesized that differentially induced primary genes in OCCM
      cells may mediate anabolic and catabolic responses. Our objective was to identify
      primary genes differentially induced by the synthetic prostanoid fluprostenol and
      IL-1 in cementoblastic cells. METHODS: Confluent OCCM cells were pretreated with
      the protein synthesis inhibitor cycloheximide followed by fluprostenol or IL-1
      for 1.5 hours. cDNA generated from each group was used for cDNA subtraction
      hybridization to identify differentially induced genes. Preferential gene
      induction was verified by Northern blot analysis. RESULTS: Thirteen fluprostenol-
      and seven IL-1-regulated genes were identified. Among the fluprostenol-induced
      genes was mitogen-activated protein (MAP) kinase phosphatase 1 (MKP1), a negative
      regulator of MAP kinase signaling. To verify the cDNA subtraction hybridization
      results, OCCM cells were treated with fluprostenol or prostaglandin F2 (PGF2),
      and MKP1 mRNA levels were determined. The 0.001 to 1 microM fluprostenol and 0.01
      to 1 microM PGF2 significantly induced MKP1 mRNA levels, which peaked at 1 hour
      of treatment and returned to baseline at 2 hours. CONCLUSIONS: Fluprostenol
      enhanced, whereas IL-1 inhibited, OCCM mineralization. Using cDNA subtraction
      hybridization, we identified primary genes that correlate with the observed
      anabolic and catabolic responses. These findings further our understanding of
      cementoblast function and suggest that differentially induced genes may mediate
      cementum formation and resorption.

PMID- 16881807
TI  - Clinical efficacy of flossing versus use of antimicrobial rinses.
AB  - BACKGROUND: Dental floss is only used by a small part of the population on a
      daily basis. Therefore, an easy, applicable alternative is needed. This
      alternative could be a mouthrinse with antimicrobial activity for daily use. The
      aim of the present study was to evaluate the efficacy of two mouthrinses in
      reducing interdental plaque and gingivitis compared to dental floss. METHODS: A
      total of 156 healthy volunteers were randomly assigned to the following groups:
      1) toothbrushing and rinsing (0.06% chlorhexidine and 0.025% fluoride); 2)
      toothbrushing and rinsing (0.1% cetylpyridiniumchloride and 0.025% fluoride); 3)
      toothbrushing and flossing; and 4) toothbrushing only (N = 39 subjects in each
      group). At baseline, the modified proximal plaque index (MPPI) and papillary
      bleeding index (PBI) were recorded. Thereafter, subjects had to brush in the
      usual manner during 8 weeks. Additionally, test groups had to rinse once a day
      (groups 1 and 2: 30 seconds) or to floss (group 3). Eight weeks after baseline,
      indices were recorded again and improvements were calculated. Analysis of
      variance (ANOVA) and the Bonferroni test served for statistical analysis.
      RESULTS: After 8 weeks, reductions for all indices were found in all groups (P
      <0.05). With respect to the MPPI, mouthrinse groups performed better than the
      control and floss groups: 1) 0.73; 2) 0.82; 3) 0.40; and 4) 0.32 (P <0.05). The
      PBI showed no statistically significant difference between groups: 1) 0.46; 2);
      0.50; 3); 0.42; and 4) 0.37. CONCLUSION: The results suggest that, in combination
      with toothbrushing, daily use of the tested mouthrinses may result in a higher
      interproximal plaque reduction than daily flossing.

PMID- 16881806
TI  - Protective effects of grape seed proanthocyanidins against oxidative stress
      induced by lipopolysaccharides of periodontopathogens.
AB  - BACKGROUND: During phagocytosis or stimulation with bacterial components,
      macrophages activate various cell processes, including the production of reactive
      oxygen species (ROS) and reactive nitrogen species (RNS), which are critical for
      successful defense against invading organisms. Increased levels of ROS/RNS create
      oxidative stress that results in tissue and bone destruction. Grape seed
      proanthocyanidins have been reported to possess a wide range of biologic
      properties against oxidative stress. In the present study, we investigated the
      effects of a grape seed proanthocyanidin extract (GSE) and commercial polyphenols
      on the production of ROS and RNS and on the protein expression of inducible
      nitric oxide synthase (iNOS) by murine macrophages stimulated with
      lipopolysaccharides (LPS) of periodontopathogens. METHODS: Macrophages (RAW
      264.7) were treated with non-toxic concentrations of either GSE or commercial
      polyphenols (gallic acid [GA] and [-]-epigallocatechin-3-gallate [EGCG]) and
      stimulated with LPS of Actinobacillus actinomycetemcomitans or Fusobacterium
      nucleatum, and iNOS expression was evaluated by immunoblotting. Nitric oxide (NO)
      production was quantified using the colorimetric Griess assay, whereas ROS
      production was measured with the fluorescent 123-dihydrorhodamine dye. RESULTS:
      GSE strongly decreased NO and ROS production and iNOS expression by LPS
      stimulated macrophages. GA also revealed a strong inhibitory effect on NO
      production without affecting iNOS expression but slightly increasing ROS
      production. EGCG showed an inhibitory effect on NO and ROS production and on iNOS
      expression by macrophages. CONCLUSION: Our findings demonstrate that
      proanthocyanidins have potent antioxidant properties and should be considered a
      potential agent in the prevention of periodontal diseases.

PMID- 16881808
TI  - Aggressive periodontitis among young Israeli army personnel.
AB  - BACKGROUND: The aim of this study was to assess the prevalence of aggressive
      periodontitis among young Israeli army recruits and to evaluate its association
      with smoking habits and ethnic origin. METHODS: The study population consisted of
      642 young army recruits (562 men [87.5%] and 80 women [12.5%]), aged 18 to 30
      years (average: 19.6 +/- 1.6 years), who arrived at a military dental clinic for
      dental examinations between January and December 2004. Subjects filled out a
      questionnaire regarding their ethnic origin and family periodontal history,
      followed by radiographs and a clinical periodontal examination of four first
      molars and eight incisors. RESULTS: Aggressive periodontitis was found in 5.9% of
      the subjects (4.3% localized and 1.6% generalized). At least one site with a
      probing depth > or =5 mm was found in 20.1% of the subjects. A radiographic
      distance between crestal bone height and the cemento-enamel junction >3 mm was
      found in 43 (6.7%) subjects. Current smokers (39.9%) (P = 0.03) and subjects of
      North African origin (P <0.0001) correlated with a high prevalence of aggressive
      periodontitis. CONCLUSION: A relatively high prevalence of aggressive
      periodontitis was found in young Israeli army recruits, which was particularly
      associated with smoking and ethnic origin.

PMID- 16881809
TI  - Microbiological composition associated with interleukin-1 gene polymorphism in
      subjects undergoing supportive periodontal therapy.
AB  - BACKGROUND: Interleukin-1 gene polymorphism (IL-1 gene) has been associated with
      periodontitis. The present study examined the subgingival microbiota by IL-1 gene
      status in subjects undergoing supportive periodontal therapy (SPT). METHODS: A
      total of 151 subjects with known IL-1 gene status (IL-1A +4845/IL-1B -3954) (IL-1
      gene) were included in this study. Clinical data and subgingival plaque samples
      (40 taxa) were collected. These taxa were determined by the checkerboard DNA-DNA
      hybridization method. RESULTS: Gender, smoking habits (n-par tests), age, and
      clinical periodontal conditions did not differ by IL-1 gene status. IL-1 gene
      negative subjects had a higher total bacterial load (mean difference, 480.4 x
      10(5); 95% confidence interval [CI], 77 to 884 x 10(5); P <0.02). The levels of
      Actinobacillus actinomycetemcomitans (mean difference, 30.7 x 10(5); 95% CI, 2.2
      to 59.5 x 10(5); P <0.05), Eubacterium nodatum (mean difference, 4.2 x 10(5); 95%
      CI, 0.6 to 7.8 x 10(5); P <0.02), Porphyromonas gingivalis (mean difference, 17.9
      x 10(5); 95% CI, 1.2 to 34.5 x 10(5); P <0.05), and Streptococcus anginosus (mean
      difference, 4.0 x 10(5); 95% CI, 0.2 to 7.2 x 10(5); P <0.05) were higher in IL-1
      gene-negative subjects, an observation specifically found at sites with probing
      depths <5.0 mm. CONCLUSIONS: Bleeding on probing did not differ by IL gene
      status, reflecting clinical SPT efficacy. IL-1 gene-negative subjects had higher
      levels of periodontal pathogens. This may suggest that among subjects undergoing
      SPT, a lower bacterial load is required in IL-1 gene-positive subjects to develop
      the same level of periodontitis as in IL-1 gene-negative subjects.

PMID- 16881810
TI  - Significance of keratinized mucosa in maintenance of dental implants with
      different surfaces.
AB  - BACKGROUND: The need for keratinized mucosa (KM) or immobile keratinized mucosa
      (i.e., attached mucosa [AM]) for the maintenance of osseointegrated endosseous
      dental implants has been controversial. The purpose of this study was to
      investigate the significance of KM in the maintenance of root-form dental
      implants with different surfaces. METHODS: A total of 339 endosseous dental
      implants in place for at least 3 years in 69 patients were evaluated. The width
      of KM and AM, modified plaque index (mPI), gingival index (GI), modified bleeding
      index (mBI), probing depth (PD), and average annual bone loss (ABL) were measured
      clinically and radiographically by a masked examiner. Based on the amounts of KM
      or AM, implants were categorized as follows: 1) KM <2 mm (KL); 2) KM > or =2 mm
      (KU); 3) AM <1 mm (AL); and 4) AM > or =1 mm (AU). Implants were further
      subdivided into the following four subgroups based on their surface
      configurations: 1) smooth surface implants (SI) with KM <2 mm (SKL); 2) SI with
      KM > or =2 mm (SKM); 3) rough surface implants (RI) with KM <2 mm (RKL); or 4) RI
      with KM > or =2 mm (RKM); or 1) SI with AM <1 mm (SAL); 2) SI with AM > or =1 mm
      (SAM); 3) RI with AM <1 mm (RAL); or 4) RI with AM > or =1 mm (RAM). The effect
      of KM or AM on clinical parameters was evaluated by comparing the different KM/AM
      groups. In addition, the significance of the presence of KM on implant prostheses
      types (i.e., fixed versus removable) and on implant locations (i.e., anterior
      versus posterior) was evaluated. RESULTS: Comparison of ABL among the four
      subgroups in KM or AM failed to reveal statistically significant differences (P
      >0.05); however, statistically significantly higher GI and mPI were present in
      SKL or SAL compared to the other three subgroups (P <0.05). GI and mPI were
      significantly higher in KL (0.94 and 1.51) than KU (0.76 and 1.26) and higher in
      AL (0.95 and 1.50) than AU (0.70 and 1.19) (P <0.05), respectively. The
      difference in GI between posterior implants with or without an adequate amount of
      KM was also significant (P <0.05). CONCLUSIONS: The absence of adequate KM or AM
      in endosseous dental implants, especially in posterior implants, was associated
      with higher plaque accumulation and gingival inflammation but not with more ABL,
      regardless of their surface configurations. Randomized controlled clinical trials
      are needed to confirm the results obtained in this retrospective clinical study.

PMID- 16881811
TI  - Comparison of interdental cleaning methods: a randomized controlled trial.
AB  - BACKGROUND: Although interdental cleaning is an integral component of home plaque
      control for periodontally involved patients, limited data exist on the
      periodontal benefits of commonly used interdental cleaning methods before
      definitive root surface debridement is undertaken. Therefore, the aim of this
      study was to compare the effects of a customized interdental brushing technique
      and a customized flossing technique on clinical periodontal outcomes prior to
      root surface debridement in chronic periodontitis cases. METHODS: This was a
      single-blind, randomized controlled clinical trial. Seventy-seven patients with
      chronic periodontitis were measured for plaque, relative interdental papillae
      level, Eastman interdental bleeding index, probing depths, and bleeding on
      probing at interdental sites and underwent a 10-minute hand scaling to remove
      easily accessible calculus deposits. Before group allocation, patients were
      advised on toothbrushing and instructed in two customized methods of interdental
      cleaning involving dental floss and precurved interdental brushes. Materials were
      supplied after random allocation. Participants were recalled at 6 and 12 weeks
      for clinical measurements, reinforcement of instructions, and fresh materials.
      RESULTS: There were significant reductions from baseline for all indices in both
      groups (P <0.01). At 6 weeks, the interdental brush group improved more than the
      floss group in every parameter (P <0.05). By 12 weeks, the changes in plaque,
      papillae level, and probing depths were significantly greater in the interdental
      brush group than the floss group (P <0.01). CONCLUSION: This trial demonstrated
      that patients were able to improve clinical periodontal outcomes by interdental
      cleaning, particularly with interdental brushes, even before thorough root
      surface debridement was undertaken.

PMID- 16881812
TI  - The influence of current and former smoking on gingival bleeding: the Hisayama
      study.
AB  - BACKGROUND: Previous studies have shown that smoking is a risk factor for
      periodontitis and that it has a suppressive effect on gingival bleeding. This
      study examined the relationship between smoking, including past smoking, and
      periodontal conditions, mainly gingival bleeding, in a community-based health
      investigation. METHODS: Smoking status was examined in 958 subjects, along with
      the quantity of tobacco currently or previously smoked (never, former light,
      former heavy, current light, and current heavy). We analyzed the influence of
      smoking on probing depth (PD), clinical attachment loss (CAL), and gingival
      bleeding on probing (BOP). RESULTS: In multivariate logistic regression analyses,
      current heavy smokers were at a significantly greater risk for having a higher
      proportion of teeth with PD > or =4 mm and a higher proportion of teeth with CAL
      > or =5 mm; however, they had a lower risk for having a high BOP than did those
      who had never smoked. Moreover, both former light and former heavy smokers had
      significantly lower risks for high BOP. When the analysis was limited to subjects
      with PD > or =4 mm, former heavy and current heavy smokers showed a significant
      suppression of high BOP compared to never smokers. CONCLUSION: This study
      suggests that smoking is significantly associated with PD and CAL and that
      current and past smoking has a suppressive effect on BOP.

PMID- 16881813
TI  - Clinical reliability of the "furcation arrow" as a diagnostic marker.
AB  - BACKGROUND: The radiographic entity known as the "furcation arrow" has long been
      used in practice even though little is known about its usefulness as a clinical
      indicator. The definitive study of the furcation arrow suggests that its presence
      on a radiograph reliably predicts furcation invasion, but this has not been
      confirmed in an in vivo investigation. The purpose of this study was to evaluate
      the furcation arrow in a clinical setting, testing the assertion that the
      furcation arrow image is an accurate predictor of furcation invasion.
      Specifically, we sought to determine the following. First, what is the prevalence
      of furcation arrow images in the radiographs of maxillary molars with
      periodontitis? Second, what is the interexaminer agreement on what constitutes a
      furcation arrow? Third, how does the presence or absence of a furcation arrow
      correlate with the true clinical status of the furcation? Fourth, what is the
      sensitivity and specificity of the furcation arrow as a diagnostic indicator?
      METHODS: Eighty-nine patients requiring surgical treatment of periodontitis in
      the maxillary molar regions were included in this study. Before surgery, one of
      five calibrated examiners viewed periapical and bitewing radiographs of the
      surgical site and recorded the presence or absence of a furcation arrow at each
      proximal furcation. Before administering anesthesia, the same examiner recorded a
      Hamp index value of each proximal furcation, with a second Hamp index taken after
      flap reflection and debridement. After surgery, each of the four remaining
      examiners independently reviewed the radiographs for furcation arrows.
      Descriptive statistical analysis was performed to correlate the appearance of the
      furcation arrow image to the actual degree of furcation invasion as determined by
      the intrasurgical Hamp index. RESULTS: A total of 164 maxillary molars were
      examined, providing 328 interproximal furcations; 111 (33.8%) furcations were
      determined at surgical debridement to have a furcation invasion of Hamp degree 1
      or greater. Of the 111 furcation invasions, 43 (38.7%) were predicted by a
      furcation arrow image seen by at least three of the five examiners. When
      comparing the appearance of the radiographic image to the extent of furcation
      invasion, 20 of 64 (31.3%) Hamp 1 furcation invasions and 23 of 47 (48.9%) Hamp 2
      and 3 furcation invasions were predicted by furcation arrows observed by at least
      three of five examiners. The multirater kappa statistic for interexaminer
      agreement on the presence or absence of the image was 0.489. The sensitivity of
      the furcation arrow image as a diagnostic marker was 38.7%, and the specificity
      was 92.2%; the positive predictive value of the image was 71.7%, and the negative
      predictive value was 74.6%. Of the 324 furcations used to compare clinical
      indices, the agreement of preanesthesia and postdebridement Hamp indices was 0%
      for degree 3, 83.7% for degree 2, and 98.4% for degree 1 furcation lesions.
      CONCLUSIONS: These data suggest that the furcation arrow has limited usefulness
      as a diagnostic marker of furcation invasion. The image is difficult to interpret
      and highly subjective and can correctly predict furcation invasions only
      approximately 70% of the time when present on the radiograph. In addition, when
      furcation invasions are truly present, the furcation arrow is seen in <40% of
      sites.

PMID- 16881814
TI  - The effect of periodontitis on biting abilities.
AB  - BACKGROUND: The aim of this study was to compare the biting abilities (bite force
      [BF] and occlusal contact area [OCA]) of chronic periodontitis patients with
      those of control patients with healthy periodontia by using pressure-sensitive
      sheets. METHODS: The study population consisted of 20 patients with chronic
      periodontitis whose initial periodontal therapy was completed and 20 control
      subjects with healthy periodontia. Periodontitis was diagnosed by radiographs and
      measurements of probing depth and clinical attachment level. Pressure-sensitive
      sheets were used for the quantitative analysis of BF and OCA. RESULTS: Both mean
      BF and OCA values were greater in the healthy control group compared to those of
      the study group. The differences between the groups were statistically
      significant at the 95% confidence level. CONCLUSION: Reduced periodontal support
      in the absence of inflammation negatively affected biting abilities.

PMID- 16881815
TI  - Connective tissue grafting on resin ionomer in localized gingival recession.
AB  - BACKGROUND: One of the main objectives of periodontal reconstructive surgery is
      the coverage of exposed roots that occur due to gingival recession. On some
      occasions, where a caries, root resorption, or amalgam restoration exists on the
      exposed root surface, the treatment planning becomes more complex. This case
      report describes the use of a subepithelial connective tissue graft (SCTG) on a
      resin ionomer-restored root surface to treat gingival recession that is
      complicated with the above-mentioned handicaps. METHODS: An amalgam restoration
      and carious lesion were removed following full-thickness flap reflection, and the
      cavity was restored with glass ionomer cement. An SCTG was placed onto the
      restoration, and the flap was coronally positioned. A porcelain crown restoration
      was performed 9 months after surgery. RESULTS: At 3-, 6-, and 9-month follow-ups,
      probing depths were reduced and gain in attachment level was obtained with no
      clinical signs of inflammation in gingiva. Monthly periodontal controls revealed
      that creeping attachment had occurred on the restoration during the follow-up
      periods. CONCLUSION: This single case report serves as a good example to show
      that SCTG can be successfully performed to treat gingival recession associated
      with a glass ionomer-restored root surface.

PMID- 16881816
TI  - Maintaining primary closure after guided bone regeneration procedures:
      introduction of a new flap design and preliminary results.
AB  - BACKGROUND: Various flap designs have been proposed by numerous authors for the
      maintenance of passive primary soft tissue closures following guided bone
      regeneration (GBR) procedures. A previous publication by the present author
      documented the maintenance of passive soft tissue primary closures 96.1% of the
      time at least 6 months after GBR therapy in all areas of the mouth. Although
      seemingly impressive, a 96.1% success rate means that there is premature membrane
      exposure 3.9% of the time. A new flap design is introduced for use in conjunction
      with previously described flap designs to lessen the incidence of premature
      membrane exposure. METHODS: A total of 173 sites treated with GBR therapy were
      examined up to 6 months postoperatively to assess the ability to maintain passive
      soft tissue primary closure. Any membrane exposure during this 6-month
      postoperative period was deemed a failure, even if the site was successfully
      treated with an implant placement and restoration. RESULTS: A total of 171 of 173
      GBR-treated sites demonstrated the maintenance of a soft tissue passive primary
      closure 6 months postoperatively, yielding a success rate of 98.8%. CONCLUSION:
      The introduction of the proposed flap design for use in conjunction with
      previously described flap designs significantly reduced the incidence of
      premature membrane exposure after a variety of GBR procedures.

PMID- 16881818
TI  - Gene regulation by chromatin structure: paradigms established in Drosophila
      melanogaster.
AB  - Studies in Drosophila melanogaster have revealed paradigms for regulating gene
      expression through chromatin structure, including mechanisms of gene activation
      and silencing. Regulation occurs at the level of individual genes, chromosomal
      domains, and entire chromosomes. The chromatin state is dynamic, allowing for
      changes in gene expression in response to cellular signals and/or environmental
      cues. Changes in chromatin result from the action of ATP-dependent chromatin
      remodeling complexes, reversible epigenetic histone modifications, and the
      incorporation of histone variants. Many of the chromatin-based transcriptional
      regulatory mechanisms discovered in D. melanogaster are evolutionarily conserved
      and therefore serve as a foundation for studies in other organisms.

PMID- 16881821
TI  - Additional comments on human rabies vaccination.

PMID- 16881822
TI  - Veterinarians as advocates for animal rights.

PMID- 16881823
TI  - What is your diagnosis?: Oblique fracture of the talus with subluxation of the
      talocalcaneal joint and avulsion fracture of the lateral malleolus.

PMID- 16881824
TI  - What is your diagnosis?: Pneumomediastinum and pneumopericardium.

PMID- 16881825
TI  - Veterinarians' role in the use of veterinary feed directive drugs in aquaculture.

PMID- 16881826
TI  - Laws and regulations concerning the confidentiality of veterinarian-client
      communication.

PMID- 16881827
TI  - Association between various physical factors and acute thoracolumbar
      intervertebral disk extrusion or protrusion in Dachshunds.
AB  - OBJECTIVE: To determine whether body weight, body condition score, or various
      body dimensions were associated with acute thoracolumbar intervertebral disk
      extrusion or protrusion and whether any of these factors were associated with
      severity of clinical signs in Dachshunds. DESIGN: Cross-sectional clinical study.
      ANIMALS: 75 Dachshunds with (n = 39) or without (36) acute thoracolumbar
      intervertebral disk extrusion or protrusion. PROCEDURES: Signalment, various body
      measurements, body weight, body condition score, and spinal cord injury grade
      were recorded at the time of initial examination. RESULTS: Mean T1-S1 distance
      and median tuber calcaneus-to-patellar tendon (TC-PT) distance were significantly
      shorter in affected than in unaffected dogs. A 1-cm decrease in T1-S1 distance
      was associated with a 2.1-times greater odds of being affected, and a 1-cm
      decrease in TC-PT distance was associated with an 11.1-times greater odds of
      being affected. Results of multivariable logistic regression also indicated that
      affected dogs were taller at the withers and had a larger pelvic circumference
      than unaffected dogs, after adjusting for other body measurements. Results of
      ordinal logistic regression indicated that longer T1-S1 distance, taller height
      at the withers, and smaller pelvic circumference were associated with more severe
      spinal cord injury. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that
      certain body dimensions may be associated with acute thoracolumbar intervertebral
      disk extrusion or protrusion in Dachshunds and, in affected dogs, with severity
      of neurologic dysfunction.

PMID- 16881829
TI  - Corneal ulceration associated with naturally occurring canine herpesvirus-1
      infection in two adult dogs.
AB  - CASE DESCRIPTION: An 8-year-old Labrador Retriever with diabetes mellitus in
      which bilateral phacoemulsification had been performed 3 weeks earlier was
      evaluated for acute onset of blepharospasm, and a 7-year-old Miniature Schnauzer
      with chronic immune-mediated thrombocytopenia was reevaluated for
      keratoconjunctivitis sicca that had been diagnosed 4 weeks earlier. CLINICAL
      FINDINGS: Dendritic corneal ulcerations were detected in both dogs. Canine
      herpesvirus-1 (CHV-1) was isolated from corneal swab specimens obtained during
      the initial evaluation of each dog and during recheck examinations performed
      until the ulcerations were healed. Canine herpesvirus-1 serum neutralization
      titers were detected in both dogs. Results of virus isolation from oropharyngeal
      and genital swab specimens were negative for both dogs. The isolated viruses were
      identified as CHV-1 via immunofluorescence, transmission electron microscopy, PCR
      assay, and gene sequencing. Negative controls for PCR assay and virus isolation
      included conjunctival swab specimens from 50 dogs without extraocular disease and
      corneal swab specimens from 50 dogs with corneal ulcers, respectively. TREATMENT
      AND OUTCOME: Lesions resolved in both dogs after topical administration of
      idoxuridine or trifluridine and discontinuation of topically administered
      immunosuppressive medications. CLINICAL RELEVANCE: To the authors' knowledge,
      this is the first report of corneal ulcerations associated with naturally
      occurring CHV-1 infection and may represent local ocular recrudescence of latent
      CHV-1 infection. The viruses isolated were identified as CHV-1, and the
      morphology, antigenicity, and genotype were similar to those for CHV-1 isolates
      obtained from a puppy that died from systemic CHV-1 infection.

PMID- 16881830
TI  - Balloon dilatation of nasopharyngeal stenosis in a dog.
AB  - CASE DESCRIPTION: A dog was examined because of a 6-month history of upper airway
      stridor that began after postoperative regurgitation of gastric contents.
      CLINICAL FINDINGS: Constant stridor was evident during inspiration and
      expiration, although it was worse during inspiration. The stridor was no longer
      evident when the dog's mouth was manually held open. Computed tomography,
      rhinoscopy, and fluoroscopy were used to confirm a diagnosis of nasopharyngeal
      stenosis. TREATMENT AND OUTCOME: The dog was anesthetized, and balloon dilatation
      of the stenosis was performed. Prednisone was prescribed for 4 weeks after the
      procedure to decrease fibrous tissue formation. Although the dog was initially
      improved, signs recurred 3.5 weeks later, and balloon dilatation was repeated.
      This time, however, triamcinolone was injected into the area of stenosis at the
      end of the dilatation procedure. Two months later, although the dog did not have
      clinical signs of stridor, a third dilatation procedure was performed because
      mild stenosis was seen on follow-up computed tomographic images; again,
      triamcinolone was injected into the area of stenosis at the end of the dilatation
      procedure. Three and 6 months after the third dilatation procedure, the dog
      reportedly was clinically normal. CLINICAL RELEVANCE: Findings suggest that
      balloon dilatation may be an effective treatment for nasopharyngeal stenosis in
      dogs.

PMID- 16881831
TI  - Comparison of two surgical techniques for management of intramural ureteral
      ectopia in dogs: 36 cases (1994-2004).
AB  - OBJECTIVE: To determine outcome associated with intramural ureteral ectopia
      treated with 1 of 2 surgical techniques (neoureterostomy with ligation of the
      distal ureteral segment vs neoureterostomy with resection of the distal ureteral
      segment) and compare results of these 2 techniques in dogs. DESIGN: Multicenter
      retrospective case series. ANIMALS: 36 dogs (15 treated with the ligation
      technique and 21 treated with the resection technique). PROCEDURES: Information
      was obtained from medical records. Long-term follow-up information was obtained
      by owner questionnaire. RESULTS: 15 of 21 (71%) dogs in the resection group and 7
      of 14 (50%) dogs in the ligation group still had urinary incontinence after
      surgery. Three of 20 (15%) dogs in the resection group and 4 of 14 (29%) dogs in
      the ligation group reportedly had multiple episodes of urinary tract infection
      following surgery. The outcome of surgery was judged to be excellent by the
      owners of 10 of 18 (56%) dogs in the resection group and 9 of 14 (64%) dogs in
      the ligation group. No significant differences were found between surgery
      treatment groups. CONCLUSIONS AND CLINICAL RELEVANCE: Results of the present
      study suggest that although most owners of dogs that undergo surgery for
      treatment of intramural ureteral ectopia consider the outcome of surgery to be
      excellent, substantial proportions of dogs will continue to have urinary
      incontinence and recurrent urinary tract infections after surgery. Findings do
      not provide any support to the hypothesis that the resection technique is
      superior to the ligation technique for management of dogs with intramural
      ureteral ectopia.

PMID- 16881832
TI  - Evaluation of intracranial meningioma resection with a surgical aspirator in
      dogs: 17 cases (1996-2004).
AB  - OBJECTIVE: To determine results of intracranial meningioma resection by use of a
      surgical aspirator and assess prognostic factors associated with intracranial
      meningiomas in dogs. DESIGN: Retrospective case series. ANIMALS: 17 dogs.
      PROCEDURES: Medical records of dogs that underwent resection of an intracranial
      meningioma by use of a surgical aspirator were reviewed. Information pertaining
      to signalment, imaging findings, clinical signs, duration of clinical signs,
      preoperative treatment, location of the tumor, results of histologic assessment,
      outcome, and necropsy results was obtained from the medical record. Clients and
      referring veterinarians were contacted via telephone for information on
      recurrence of clinical signs and postoperative survival time. RESULTS: 16 dogs
      were > 7 years of age, and all 17 dogs had seizures before surgery. The most
      commonly affected breed was the Golden Retriever, represented by 6 of the 17
      dogs. Median survival time was 1,254 days. Of the data collected, only histologic
      subtype of the tumor was prognostic. Analysis of survival times according to
      histologic tumor subtypes indicated that the order from most brief to longest was
      as follows: anaplastic, 0 days; fibroblastic, 10 days; psammomatous, > 313 days;
      meningothelial, > 523 days; and transitional, 1,254 days. CONCLUSIONS AND
      CLINICAL RELEVANCE: Use of a surgical aspirator to resect intracranial
      meningiomas in dogs was associated with longer survival times than those achieved
      with traditional surgery alone or traditional surgery combined with radiation
      therapy. Dogs with meningothelial, psammomatous, or transitional intracranial
      meningioma subtypes appeared to have a better prognosis than dogs with other
      subtypes of meningioma.

PMID- 16881833
TI  - Evaluation of factors associated with survival in dogs with untreated nasal
      carcinomas: 139 cases (1993-2003).
AB  - OBJECTIVE: To evaluate factors associated with survival in dogs with nasal
      carcinomas that did not receive treatment or received only palliative treatment.
      DESIGN: Retrospective case series. ANIMALS: 139 dogs with histologically
      confirmed nasal carcinomas. PROCEDURES: Medical records, computed tomography
      images, and biopsy specimens of nasal carcinomas were reviewed. Only dogs that
      were not treated with radiation, surgery, chemotherapy, or immunotherapy and that
      survived > or = 7 days from the date of diagnosis were included. The Kaplan-Meier
      method was used to estimate survival time. Factors potentially associated with
      survival were compared by use of log-rank and Wilcoxon rank sum tests.
      Multivariable survival analysis was performed by use of the Cox proportional
      hazards regression model. RESULTS: Overall median survival time was 95 days (95%
      confidence interval [CI], 73 to 113 days; range, 7 to 1,114 days). In dogs with
      epistaxis, the hazard of dying was 2.3 times that of dogs that did not have
      epistaxis. Median survival time of 107 dogs with epistaxis was 88 days (95% CI,
      65 to 106 days) and that of 32 dogs without epistaxis was 224 days (95% CI, 54 to
      467 days). CONCLUSIONS AND CLINICAL RELEVANCE: The prognosis of dogs with
      untreated nasal carcinomas is poor. Treatment strategies to improve outcome
      should be pursued.

PMID- 16881834
TI  - Outcome of desmoplasty and fasciotomy for desmitis involving the origin of the
      suspensory ligament in horses: 27 cases (1995-2004).
AB  - OBJECTIVE: To determine outcome of percutaneous ultrasound-guided desmoplasty
      with simultaneous fasciotomy for proximal suspensory desmitis (ie, desmitis of
      the origin of the suspensory ligament) in horses that have not responded to stall
      rest. DESIGN: Retrospective case series. ANIMALS: 27 horses. PROCEDURES: Medical
      records of horses with proximal suspensory desmitis treated by means of
      desmoplasty with fasciotomy were reviewed. Follow-up information was obtained
      through telephone conversations with owners and trainers of the horses or by
      examination of horses at the hospital. RESULTS: 23 of the 27 (85%) horses,
      including 3 of 4 horses with forelimb lesions and 20 of 23 horses with hind limb
      lesions, were able to return to full work after surgery and rehabilitation. All
      horses had ultrasonographic evidence of healing of suspensory ligament lesions.
      CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that desmoplasty with
      fasciotomy is a viable treatment option in horses with proximal suspensory
      desmitis that have not responded to stall rest.

PMID- 16881835
TI  - Effect of continuous intravenous administration of a 50% dextrose solution on
      phosphorus homeostasis in dairy cows.
AB  - OBJECTIVE: To determine the effect of continuous IV administration of 50%
      dextrose solution on phosphorus homeostasis in lactating dairy cows. DESIGN:
      Clinical trial. ANIMALS: 4 multiparous Jersey cows. PROCEDURES: Cows were
      administered 50% dextrose solution IV (0.3 g/kg/h [0.14 g/lb/h]) for 5 days.
      Plasma concentrations of glucose, immune-reactive insulin (IRI), and phosphorus
      were determined before, during, and for 72 hours after dextrose infusion.
      Phosphorus intake and losses of phosphorus in urine, feces, and milk were
      determined. Each cow received a sham treatment that included instrumentation and
      sampling but not administration of dextrose. RESULTS: Plasma glucose, IRI, and
      phosphorus concentrations were stable during sham treatment. Plasma phosphorus
      concentration decreased rapidly after onset of dextrose infusion, reaching a
      nadir in 24 hours and remaining less than baseline value for 36 hours. Plasma
      phosphorus concentration increased after dextrose infusion was stopped, peaking
      in 6 hours. Urinary phosphorus excretion did not change during dextrose infusion,
      but phosphorus intake decreased because of reduced feed intake, followed by
      decreased fecal phosphorus loss and milk yield. Rapid changes in plasma
      phosphorus concentration at the start and end of dextrose infusion were
      temporally associated with changes in plasma glucose and IRI concentrations and
      most likely caused by compartmental shifts of phosphorus. CONCLUSIONS AND
      CLINICAL RELEVANCE: Hypophosphatemia developed in response to hyperglycemia or
      hyperinsulinemia in dairy cows administered dextrose via continuous IV infusion.
      Veterinarians should monitor plasma phosphorus concentration when administering
      dextrose in this manner, particularly in cows with decreased appetite or
      preexisting hypophosphatemia.

PMID- 16881837
TI  - Comparison of techniques for determination of chondrocyte viability after thermal
      injury.
AB  - OBJECTIVE: To compare 2 methods of quantitating chondrocyte viability and to
      determine chondrocyte response to thermal injury over time. SAMPLE POPULATION:
      108 stifle joints from 54 adult rats. PROCEDURES: Cartilage from the distal
      aspect of the femur was treated ex vivo with radiofrequency energy at a probe
      setting that would result in immediate partial-thickness chondrocyte death;
      untreated sections served as controls. Explants were cultured, and cell viability
      was compared by use of lactate dehydrogenase (LDH) histochemical staining and
      calcein AM and ethidium homodimer-1 confocal laser microscopy (CLM) cell
      viability staining. Terminal deoxynucleotidyl transferase-mediated X-dUTP nick
      end labeling (TUNEL) was used to detect apoptosis. All labeling studies were
      performed 0, 1, 3, 7, 14, and 21 days after treatment. RESULTS: In the treated
      tissues, a greater percentage of viable cells were found with CLM, compared with
      LDH staining. This result contrasted that of control tissues in which LDH
      staining indicated a greater percentage of live cells than CLM. The greatest
      number of TUNEL-positive chondrocytes was present at day 3, declining at later
      time intervals. CONCLUSIONS AND CLINICAL RELEVANCE: CLM and LDH histochemistry
      techniques yield different absolute numbers of live and dead cells, resulting in
      differing percentages of live or dead cells with each technique. These
      differences may be related to the enzymes responsible for activation in each
      technique and the susceptibility of these enzymes to thermal injury. Results of
      TUNEL indicate that apoptosis contributes to chondrocyte death after thermal
      injury, with a peak signal identified 3 days after insult.

PMID- 16881838
TI  - Use of infrared spectroscopy for diagnosis of traumatic arthritis in horses.
AB  - OBJECTIVE: To evaluate use of infrared spectroscopy for diagnosis of traumatic
      arthritis in horses. ANIMALS: 48 horses with traumatic arthritis and 5 clinically
      and radiographically normal horses. PROCEDURES: Synovial fluid samples were
      collected from 77 joints in 48 horses with traumatic arthritis. Paired samples
      (affected and control joints) from 29 horses and independent samples from an
      affected (n = 12) or control (7) joint from 19 horses were collected for model
      calibration. A second set of 20 normal validation samples was collected from 5
      clinically and radiographically normal horses. Fourier transform infrared spectra
      of synovial fluids were acquired and manipulated, and data from affected joints
      were compared with controls to identify spectroscopic features that differed
      significantly between groups. A classification model that used linear
      discriminant analysis was developed. Performance of the model was determined by
      use of the 2 validation datasets. RESULTS: A classification model based on 3
      infrared regions classified spectra from the calibration dataset with overall
      accuracy of 97% (sensitivity, 93%; specificity, 100%). The model, with cost
      adjusted prior probabilities of 0.60:0.40, yielded overall accuracy of 89%
      (sensitivity, 83%; specificity, 100%) for the first validation sample dataset and
      100% correct classification of the second set of independent normal control
      joints. CONCLUSIONS AND CLINICAL RELEVANCE: The infrared spectroscopic patterns
      of fluid from joints with traumatic arthritis differed significantly from the
      corresponding patterns for controls. These alterations in absorption patterns may
      be used via an appropriate classification algorithm to differentiate the spectra
      of affected joints from those of controls.

PMID- 16881839
TI  - Effect of trotting velocity on work patterns of the hind limbs of Greyhounds.
AB  - OBJECTIVE: To quantify the effects of trotting velocity on joint angular
      excursions, net joint moments, and powers across the hind limb joints in
      Greyhounds. ANIMALS: 5 healthy Greyhounds with no history of lameness of the hind
      limbs. PROCEDURES: Small reflective markers were applied to the skin over the
      joints of the hind limbs, and a 4-camera kinematic system was used to record
      positional data at 200 Hz in tandem with force platform data while the dogs
      trotted on a runway at slow, medium, and fast velocities. Breed-specific
      morphometric data were combined with kinematic and force data in an inverse
      dynamics solution for net joint moments and powers at the hip, stifle, tarsal,
      and metatarsophalangeal joints. RESULTS: Angle, moment, and power patterns at the
      various joints were conserved among the 3 velocities. With increasing velocity,
      moments and powers at the tarsal, stifle, and hip joints during the stance phase
      were increased in amplitude, whereas amplitudes during the swing phase were not.
      The main contributors to increased velocity were the hip extensors and stifle
      flexors during the early part of the stance phase and the tarsal extensors during
      the late part of the stance phase. CONCLUSIONS AND CLINICAL RELEVANCE: Increases
      in trotting velocity in Greyhounds do not alter the basic patterns of work and
      power for various joints of the hind limbs, but local burst amplitudes during the
      stance phase increase incrementally.

PMID- 16881840
TI  - Gross, histologic, and gene expression characteristics of osteoarthritic
      articular cartilage of the metacarpal condyle of horses.
AB  - OBJECTIVE: To identify patterns and correlations of gross, histologic, and gene
      expression characteristics of articular cartilage from horses with
      osteoarthritis. ANIMALS: 10 clinically normal horses and 11 horses with
      osteoarthritis of the metacarpal condyles. PROCEDURES: Metacarpophalangeal joints
      were opened and digitally photographed, and gross lesions were scored and
      quantified. Representative cartilage specimens were stained for histologic
      scoring. Total RNA from dorsal and palmar articular surfaces was processed on an
      equine gene expression microarray. RESULTS: Histologic scores were greater in
      both regions of osteoarthritic joints, compared with corresponding regions in
      control joints. Cartilage from the palmar aspect of diseased joints had the
      highest histologic scores of osteoarthritic sites or of either region in control
      joints. A different set of genes for dorsal and palmar osteoarthritis was
      identified for high and low gene expression. Articular cartilage from the dorsal
      region had surface fraying and greater expression of genes coding for collagen
      matrix components and proteins with anti-apoptotic function, compared with
      control specimens. Articular cartilage from the palmar region had greater
      fraying, deep fissures, and less expression of genes coding for glycosaminoglycan
      matrix formation and proteins with anti-apoptotic function, compared with
      cartilage from disease-free joints and the dorsal aspect of affected joints.
      CONCLUSIONS AND CLINICAL RELEVANCE: Metacarpal condyles of horses with naturally
      occurring osteoarthritis had an identifiable and regional gene expression
      signature with typical morphologic features.

PMID- 16881841
TI  - Genomic expression patterns of mitral valve tissues from dogs with degenerative
      mitral valve disease.
AB  - OBJECTIVE: To evaluate global genome expression patterns of mitral valve tissues
      from dogs with degenerative mitral valve disease (DMVD). SAMPLE POPULATION:
      Anterior mitral valve leaflets of 4 dogs with severe DMVD and 4 healthy control
      dogs. PROCEDURES: Transcriptional activities of 23,851 canine DNA sequences were
      determined by use of an oligonucleotide microarray. Genome expression patterns of
      tissue from dogs with DMVD were evaluated by measuring the relative amount of
      complementary RNA hybridization to the microarray probes and by comparing it with
      gene expression from healthy control dogs. RESULTS: 229 transcripts were
      differentially expressed (>or= 2-fold change). In dogs with DMVD, expression of
      159 transcripts was upregulated and expression of 70 transcripts was
      downregulated. Of the 229 transcripts, 152 genes could be specifically
      identified. These genes were grouped into 1 of 9 categories on the basis of their
      primary physiologic function. Grouping revealed that pathways involving cell
      signaling, inflammation, extracellular matrix, immune function, cell defense, and
      metabolism were generally upregulated. Inflammatory cytokines and the serotonin
      transforming growth factor-beta pathway were identified as contributory to the
      pathophysiologic aspects of DMVD. CONCLUSIONS AND CLINICAL RELEVANCE: Evaluation
      of global expression patterns provides a molecular portrait of mitral valve
      disease, yields insight into the pathophysiologic aspects of DMVD, and identifies
      intriguing genes and pathways for further study.

PMID- 16881842
TI  - Neurohormonal, hemodynamic, and electrocardiographic evaluations of healthy dogs
      receiving long-term administration of doxorubicin.
AB  - OBJECTIVE: To evaluate diagnostic testing that could be used to establish an
      early diagnosis of cardiotoxicosis induced by long-term administration of
      doxorubicin. ANIMALS: 13 adult mixed-breed dogs. Procedures-7 dogs were
      administered doxorubicin chloride (30 mg/m(2), IV, q 21 d for 168 days
      [cumulative dose, 240 mg/m(2)]), and 6 dogs received saline (0.9% NaCl) solution
      (5 mL, IV, q 21 d for 168 days; control group). Echocardiography, ECG, arterial
      blood pressure, plasma renin activity (PRA), and plasma concentrations of
      norepinephrine and brain natriuretic peptide (BNP) were assessed before each
      subsequent administration of doxorubicin and saline solution. RESULTS: Dogs that
      received doxorubicin had a significant decrease in R-wave amplitude, compared
      with values for the control group, from 30 to 210 mg/m(2). Doxorubicin-treated
      dogs had decreases in fractional shortening and left ventricular ejection
      fraction evident as early as 30 mg/m(2), but significant differences between
      groups were not detected until 90 mg/m(2)was reached. There was also a
      significant increase in PRA (>or= 120 mg/m(2)) and left ventricular end-systolic
      and end-diastolic dimensions (>or= 60 and >or= 180 mg/m(2), respectively).
      Systemic arterial pressure, remaining echocardiographic variables, and
      concentrations of norepinephrine and BNP had significant variations, but of no
      clinical importance, during doxorubicin administration. CONCLUSIONS AND CLINICAL
      RELEVANCE: Doxorubicininduced cardiotoxicosis developed at 120 mg/m(2), but there
      were no clinical signs of dilated cardiomyopathy or congestive heart failure.
      Echocardiography and determination of PRA were able to detect early cardiac
      alterations during the development of dilated cardiomyopathy, despite apparently
      differing degrees of sensitivity to development of doxorubicin-induced
      cardiotoxicosis.

PMID- 16881843
TI  - Evaluation of the sensitivity and specificity of four laboratory tests for
      detection of occult blood in cockatiel (Nymphicus hollandicus) excrement.
AB  - OBJECTIVE: To compare sensitivity and specificity of cytologic examination and 3
      chromogen tests for detection of occult blood in cockatiel (Nymphicus
      hollandicus) excrement. ANIMALS: 20 adult cockatiels. PROCEDURES: Pooled blood
      from birds was divided into whole blood and lysate aliquots. Excrement was mixed
      with each aliquot in vitro to yield 6 hemoglobin (Hb) concentrations (range,
      0.375 to 12.0 mg of Hb/g of excrement). For the in vivo portion of the study,
      birds were serially gavaged with each aliquot separately at 5 doses of Hb (range,
      2.5 to 40 mg/kg). Three chromogen tests and cytologic examination were used to
      test excrement samples for occult blood. Sensitivity, specificity, and observer
      agreement were calculated. RESULTS: In vitro specificity ranged from 85%to 100%
      for the 3 chromogen tests and was 100% for cytologic examination. Sensitivity was
      0% to 35% for cytologic examination and 100% for the 3 chromogen tests on samples
      containing >or= 1.5 mg of Hb/g of excrement. In vivo specificity was 100%, 90%,
      65%, and 45% for cytologic examination and the 3 chromogen tests, respectively.
      Sensitivity was 0% to 5% for cytologic examination and >or= 75% for all 3
      chromogen tests after birds received doses of Hb >or= 20 mg/kg. Observer
      agreement was lowest for cytologic examination. CONCLUSIONS AND CLINICAL
      RELEVANCE: Chromogen tests were more useful than cytologic examination for
      detection of occult blood in cockatiel excrement. The best combination of
      sensitivity, specificity, and observer agreement was obtained by use of a
      chromogen test.

PMID- 16881844
TI  - Serum concentrations of calcium, phosphorus, magnesium and calciotropic hormones
      in donkeys.
AB  - OBJECTIVE: To provide reference values for serum biochemical variables that are
      used for evaluation of mineral metabolism in donkeys and compare values with
      those in horses. ANIMALS: 18 donkeys and 18 horses. PROCEDURES: Total calcium
      (tCa), total magnesium (tMg), and inorganic phosphorus (P) concentrations were
      measured in serum samples via spectrophotometry. Ionized calcium (iCa) and
      magnesium (iMg) concentrations were quantified with selective electrodes. By use
      of a micropartition system, tCa and tMg were fractionated to separate protein
      bound (pCa, pMg) and ultrafiltrable fractions. Complexed calcium (cCa) and
      magnesium (cMg) concentrations were calculated by substracting ionized fractions
      from ultrafiltrable fractions. Parathyroid hormone (PTH) and calcitriol (CTR)
      concentrations were measured via radioimmunoassay. RESULTS: Serum tCa
      concentration in donkeys (3.37 +/- 0.21 mmol/L) was composed of pCa (1.59 +/-
      0.21 mmol/L [47.0 +/- 4.2%]), iCa (1.69 +/- 0.04 mmol/L [50.4 +/- 3.0%]), and cCa
      (0.09 +/- 0.08 mmol/L [2.6 +/- 2.9%]). Serum tMg concentration (1.00 +/- 0.08
      mmol/L) was fractioned in pMg (0.23 +/- 0.08 mmol/L [23.4 +/- 8.1%]), iMg (0.59
      +/- 0.04 mmol/L [58.8 +/- 5.1%]), and cMg (0.18 +/- 0.08 mmol/L [17.8 +/- 7.2%]).
      Serum concentrations of P (1.14 +/- 0.30 mmol/L), PTH (20.4 +/- 21.2 pg/mL), and
      CTR (13.4 +/- 5.9 pg/mL) were determined. CONCLUSIONS AND CLINICAL RELEVANCE:
      Serum variables of mineral metabolism in donkeys were within reference ranges for
      horses. However, when compared with horses, donkeys had higher iCa, cMg, and CTR
      and lower pMg and PTH concentrations.

PMID- 16881845
TI  - Genotypic relatedness of staphylococcal strains isolated from pustules and
      carriage sites in dogs with superficial bacterial folliculitis.
AB  - OBJECTIVE: To determine whether staphylococcal isolates cultured from pustules
      and carriage sites in dogs with superficial bacterial folliculitis were
      genotypically the same strain by use of pulsed-field gel electrophoresis (PFGE).
      ANIMALS: 40 dogs with superficial bacterial folliculitis. PROCEDURES: Samples
      were obtained from 3 pustules and 3 carriage sites (anus, axillary skin, and
      nasal mucosa). Bacterial culture, morphologic identification, Gram staining,
      catalase and coagulase tests, speciation, and PFGE were performed. RESULTS: Of
      246 isolates, 203 were Staphylococcus intermedius, 5 were Staphylococcus aureus,
      15 were Staphylococcusspp, and 22 were coagulase-negative staphylococcal
      isolates. No dog had an isolate with the same PFGE pattern as an isolate from
      another dog. Coagulase-positive isolates from multiple pustules and multiple
      carriage sites had the same PFGE pattern in 37 of 39 (94.9%) and 22 of 39 (56.4%)
      dogs, respectively. Coagulase-positive staphylococcal isolates from at least 1
      pustule had the same PFGE pattern as an isolate from at least 1 carriage site in
      34 of 36 (94.4%) dogs. Ninety-seven of 116 (83.6%) coagulase-positive
      staphylococcal isolates from pustules had the same PFGE pattern as an isolate
      from at least 1 carriage site. Sixty-nine of 91 (75.8%) coagulase-positive
      staphylococcal isolates from carriage sites had the same PFGE pattern as an
      isolate from at least 1 pustule. CONCLUSIONS AND CLINICAL RELEVANCE:
      Coagulasepositive staphylococcal strains were heterogeneous among dogs with
      superficial bacterial folliculitis. In individual dogs, strains from multiple
      pustules were genotypically the same, and strains from pustules were
      genotypically the same as strains from carriage sites.

PMID- 16881846
TI  - Sectional anatomic and magnetic resonance imaging features of coelomic structures
      of loggerhead sea turtles.
AB  - OBJECTIVE: To compare cross-sectional anatomic specimens with images obtained via
      magnetic resonance imaging (MRI) of the coelomic structures of loggerhead sea
      turtles (Caretta caretta). ANIMALS: 5 clinically normal live turtles and 5 dead
      turtles. PROCEDURES: MRI was used to produce T1- and T2- weighted images of the
      turtles, which were compared with gross anatomic sections of 3 of the 5 dead
      turtles. The other 2 dead turtles received injection with latex and were
      dissected to provide additional cardiovascular anatomic data. RESULTS: The
      general view on the 3 oriented planes provided good understanding of cross
      sectional anatomic features. Likewise, major anatomic structures such as the
      esophagus, stomach, lungs, intestine (duodenum and colon), liver, gallbladder,
      spleen, kidneys, urinary bladder, heart, bronchi, and vessels could be clearly
      imaged. It was not possible to recognize the ureters or reproductive tract.
      CONCLUSIONS AND CLINICAL RELEVANCE: By providing reference information for
      clinical use, MRI may be valuable for detailed assessment of the internal
      anatomic structures of loggerhead sea turtles. Drawbacks exist in association
      with anesthesia and the cost and availability of MRI, but the technique does
      provide excellent images of most internal organs. Information concerning
      structures such as the pancreas, ureters, intestinal segments (jejunum and
      ileum), and the reproductive tract is limited because of inconsistent
      visualization.

PMID- 16881847
TI  - Evaluation of nonunion fractures in dogs by use of B-mode ultrasonography, power
      Doppler ultrasonography, radiography, and histologic examination.
AB  - OBJECTIVE: To investigate the use of ultrasonography to assess nonunion of
      fractures in dogs and to compare results of ultrasonography, radiography, and
      histologic examination. SAMPLE POPULATION: 8 nonunion fractures in 6 dogs (1 each
      in 5 dogs and 3 in 1 dog); dogs ranged from 7 to 94 months of age and weighed 6
      to 30 kg. PROCEDURES: Diagnostic assessment consisted of complete clinical and
      orthopedic examinations, radiography, B-mode (brightness mode) ultrasonography,
      and power Doppler ultrasonography. Biopsy samples were obtained during surgery
      for histologic examination. They were stained with H&E and immunolabeled by use
      of anti-CD31 antibodies. Correlations of power Doppler score, power Doppler
      count, vessel area, and radiographic prediction with the mean number of vessels
      counted per hpf were derived. RESULTS: Radiographically, 7 of 8 nonunion
      fractures were diagnosed as atrophic and were therefore estimated to be
      nonviable. Vascularity of nonunion fractures during power Doppler ultrasonography
      ranged from nonvascularized to highly vascularized. Absolute vessel count during
      histologic examination ranged from 0 to 63 vessels/hpf; 5 nonunion sites had a
      mean count of > 10 vessels/hpf. Vascularity during power Doppler ultrasonography
      was highly correlated with the number of vessels per hpf, whereas the correlation
      between the radiographic assessment and histologic evaluation was low.
      CONCLUSIONS AND CLINICAL RELEVANCE: Radiographic prediction of the viability of
      nonunion fractures underestimated the histologically assessed vascularity of the
      tissue. Power Doppler ultrasonography provided a more accurate estimation of the
      viability of the tissue and therefore the necessity for debridement and
      autografts during revision surgery.

PMID- 16881848
TI  - Effect of four sedative and anesthetic protocols on quantitative thyroid
      scintigraphy in euthyroid cats.
AB  - OBJECTIVES: To determine the effect of sedation and anesthesia on thyroid and
      salivary gland uptake of technetium Tc 99m pertechnetate ((99m)TcO(4)) in
      euthyroid cats. ANIMALS: 6 euthyroid cats. PROCEDURES: Thyroid scintigraphy was
      performed by use of a high-resolution low-energy parallel-hole collimator after
      IV injection of 117 to 133 MBq (3.16 to 3.59 mCi) of (99m)TcO(4)(-). The
      procedure was performed 4 times on each cat during different sedative and
      anesthetic protocols in a rotating schedule as follows: propofol, ketamine
      midazolam-atropine, ketaminemidazolam, and medetomidine. Regions of interest were
      drawn around thyroid and salivary glands and counts corrected for background and
      decay. Percentage of (99m)TcO(4)(-) uptake in salivary and thyroid glands and
      thyroid-to-salivary gland (99m)TcO(4)(-) uptake ratio were calculated at 20 and
      40 minutes. Relative effects of anesthesia and sedation on salivary and thyroid
      gland (99m)TcO(4)(-) uptake were compared. RESULTS: Significant differences among
      sedativeanesthetic protocols were found for thyroid gland (99m)TcO(4)(-) uptake,
      salivary gland (99m)TcO(4)(-) uptake, and thyroid-to-salivary gland (99m)TcO(4)(
      ) uptake ratio. Thyroid gland (99m)TcO(4)(-) uptake for the ketamine-midazolam
      protocol at 20 and 40 minutes after (99m)TcO(4)(-) administration was
      significantly higher than for the propofol protocol. A significant difference in
      salivary gland(99m) TcO(4)(-) uptake was found between ketamine-midazolam and
      ketamine-midazolam-atropine protocols at 40 minutes. The thyroid-to-salivary
      gland (99m)TcO(4)(-) uptake ratio for the ketamine-midazolam protocol was
      significantly higher at 40 minutes than for propofol or ketamine-midazolam
      atropine protocols. CONCLUSIONS AND CLINICAL RELEVANCE: Sedation and anesthesia
      have a significant effect on thyroid and salivary gland (99m)TcO(4) uptake in
      euthyroid cats that may interfere with thyroid scintigraphic image
      interpretation.

PMID- 16881849
TI  - Quantitative mRNA analysis of adrenergic receptor subtypes in the intestines of
      healthy dairy cows and dairy cows with cecal dilatation-dislocation.
AB  - OBJECTIVE: To investigate the distribution of mRNA coding for 9 adrenoceptor
      subtypes in the intestines of healthy dairy cows and cows with cecal
      dilatationdislocation (CDD). SAMPLE POPULATION: Full-thickness specimens of the
      intestinal wall were obtained from the ileum, cecum, proximal loop of the
      ascending colon (PLAC), and external loop of the spiral colon (ELSC) of 15 cows
      with CDD (group 1) and 15 healthy (control) cows (group 2, specimens collected
      during laparotomy; group 3, specimens collected after slaughter). PROCEDURES:
      Concentrations of mRNA for 9 adrenoceptor subtypes (alpha(1A), alpha(1B),
      alpha(1D), alpha(2AD), alpha(2B), alpha(2C), beta(1), beta(2), and beta(3)) were
      measured by quantitative real-time reverse transcriptase-PCR assay. Results were
      expressed relative to mRNA expression of a housekeeping gene. RESULTS: Expression
      of mRNA for alpha(1B)-, alpha(2AD)-, alpha(2B)-, beta(1)-, and beta(2)
      adrenoceptors was significantly lower in cows with CDD than in control cows. In
      the ileum, these receptors all had lower mRNA expression in cows with CDD than in
      control cows. The same effect was detected in the ELSC for mRNA for alpha(2AD)-,
      alpha(2B)-, beta(1)-, and beta(2)-adrenoceptors, and in the cecum and PLAC for
      alpha(2B)- and beta(2)-adrenoceptors. Groups did not differ significantly for
      alpha(1A)-adrenoceptors. The mRNA expression for alpha(1D)-, alpha(2C)-, and
      beta(3)-adrenoceptors was extremely low in all groups. CONCLUSIONS AND CLINICAL
      RELEVANCE: Differences in expression of mRNA coding for adrenoceptors, most
      pronounced in the ileum and spiral colon, between cows with CDD and control cows
      support the hypothesis of an implication of adrenergic mechanisms in the
      pathogenesis of CDD in dairy cows.

PMID- 16881851
TI  - Effect of mitotane on pituitary corticotrophs in clinically normal dogs.
AB  - OBJECTIVE: To evaluate the effects of mitotane administration on the function and
      morphology of pituitary corticotrophs in clinically normal dogs. ANIMALS: 12
      clinically normal adult Beagles. PROCEDURES: Dogs were randomly assigned to the
      control group or the mitotane treatment group. In mitotane treatment group dogs,
      mitotane was administered for 1 month. In both groups, ACTH stimulation testing
      and corticotrophin-releasing hormone (CRH) stimulation testing were performed.
      Magnetic resonance imaging (MRI) of the pituitary gland and brain was performed
      in mitotane treatment group dogs before and after administration of mitotane.
      After CRH stimulation testing and MRI, dogs were euthanatized and the pituitary
      gland and adrenal glands were excised for gross and histologic examination.
      RESULTS: ACTH concentrations in mitotane treatment group dogs were significantly
      higher than in the control group dogs following CRH stimulation. Magnetic
      resonance imaging revealed that pituitary glands were significantly larger in
      treatment group dogs after administration of mitotane, compared with before
      administration. On gross and histologic examinations, the adrenal cortex was
      markedly atrophied. Immunohistochemistry revealed hypertrophy of corticotrophs in
      pituitary glands of mitotane treatment group dogs. CONCLUSIONS AND CLINICAL
      RELEVANCE: These findings indicate that inhibition of the adrenal cortex by
      continuous administration of mitotane leads to functional amplification and
      morphologic enhancement of corticotrophs in clinically normal dogs. In instances
      of corticotroph adenoma, hypertrophy of individual corticotrophs induced by
      mitotane may greatly facilitate enlargement of the pituitary gland and increases
      in ACTH secretion.

PMID- 16881850
TI  - Effect of suckling isotonic or hypertonic solutions of sodium bicarbonate or
      glucose on abomasal emptying rate in calves.
AB  - OBJECTIVE: To determine and compare the abomasal emptying rates in calves
      suckling milk replacer or an isotonic or hypertonic solution of NaHCO(3) or
      glucose. ANIMALS: 5 male Holstein-Friesian calves that were < 30 days of age.
      PROCEDURES: Calves were fed 2 L of milk replacer or isotonic (300 mOsm/L) or
      hypertonic (600 mOsm/L) solutions of NaHCO(3) or glucose containing acetaminophen
      (50 mg/kg). Venous blood samples and transabdominal ultrasonographic abomasal
      dimensions were obtained periodically after feeding, and abomasal luminal pH was
      continuously monitored by placement of a luminal pH electrode through an abomasal
      cannula. Abomasal emptying rate was assessed by the time to maximal plasma
      acetaminophen concentration, ultrasonographic determination of the half-time of
      abomasal emptying, and the time for luminal pH to return to within 1 pH unit of
      the preprandial value. RESULTS: Hypertonic NaHCO(3) solution was emptied slower
      than an isotonic NaHCO(3) solution, isotonic glucose solution was emptied slower
      than an isotonic NaHCO(3) solution, and hypertonic glucose solution emptied
      slower than an isotonic glucose solution. CONCLUSIONS AND CLINICAL RELEVANCE: An
      electrolyte solution for oral administration with a high osmolarity and glucose
      concentration may lead to a slower resuscitation of dehydrated diarrheic calves
      because such solutions decrease the abomasal emptying rate and therefore the rate
      of solution delivery to the small intestine. Whether slowing of the abomasal
      emptying rate in dehydrated diarrheic calves suckling an oral electrolyte
      solution is clinically important remains to be determined.

PMID- 16881852
TI  - Exclusion of linkage of the RYR1, CACNA1S, and ATP2A1 genes to recurrent
      exertional rhabdomyolysis in Thoroughbreds.
AB  - OBJECTIVE: To determine whether there was genetic linkage between the recurrent
      exertional rhabdomyolysis (RER) trait in Thoroughbred horse pedigrees and DNA
      markers in genes (the sarcoplasmic reticulum calcium release channel [RYR1] gene,
      the sarcoplasmic reticulum calcium ATPase [ATP2A1] gene, and the transverse
      tubule dihydropyridine receptor-voltage sensor [CACNA1S] gene) that are important
      in myoplasmic calcium regulation. ANIMALS: 34 horses in the University of
      Minnesota RER resource herd and 62 Thoroughbreds from 3 families of Thoroughbreds
      outside of the university in which RER-affected status was assigned after 2 or
      more episodes of ER had been observed. PROCEDURES: Microsatellite DNA markers
      from the RYR1, ATP2A1, and CACNA1S gene loci on equine chromosomes 10, 13, and 30
      were identified. Genotypes were obtained for all horses in the 4 families
      affected by RER, and data were used to test for linkage of these 3 loci to the
      RER phenotype. RESULTS: Analysis of the RYR1, CACNA1S, and ATP2A1 microsatellites
      excluded a link between those markers and the RER trait. CONCLUSIONS AND CLINICAL
      RELEVANCE: It is likely that the heritable alterations in muscle contractility
      that are characteristic of RER are caused by a gene that is not yet known to
      cause related muscle disease in other species.

PMID- 16881853
TI  - Antemortem detection of latent infection with neuropathogenic strains of equine
      herpesvirus-1 in horses.
AB  - OBJECTIVE: To evaluate a technique for identifying horses latently infected with
      neuropathogenic strains of equine herpesvirus-1 (EHV-1). ANIMALS: 36 adult mares,
      24 of which were experimentally infected as weanlings with neuropathogenic or
      nonneuropathogenic EHV-1. PROCEDURES: Mandibular lymph node (MLN) tissue was
      obtained from each horse via biopsy during general anesthesia. Purified DNA from
      MLNs was tested for EHV-1 DNA by use of a magnetic bead, sequencecapture, nested
      PCR assay. For MLNs that contained EHV-1 DNA, the 256-bp DNA fragments amplified
      via sequence-capture nested PCR were sequenced to determine the nucleotide at the
      polymorphic site that determines pathotype (ie, neuropathotype [G(2254)] or non
      neuropathotype [A(2254)]). RESULTS: Latent viral DNA was detected in 26 of the 36
      (72%) mares tested. Neuropathogenic and nonneuropathogenic EHV-1 genotypes were
      detected in the latently infected horses. In each mare previously infected with
      known EHV-1 pathotypes, the open reading frame 30 genotype of latent EHV-1 was
      identical to that of the strain that had been inoculated 4 to 5 years earlier.
      Latent viral DNA was detected in 10 of the 12 mares that were inoculated as
      weanlings with neuropathogenic strains of EHV-1. The detection rate of the
      sequence-capture PCR method for EHV-1 latency was double that of conventional
      nested or realtime PCR assays performed on the same MLN DNA preparations.
      CONCLUSIONS AND CLINICAL RELEVANCE: The magnetic bead, sequence-capture, nested
      PCR technique enabled low-threshold detection of DNA from latent neuropathogenic
      strains of EHV-1 in MLN specimens from live horses. The technique may be used to
      screen horses for latent neuropathogenic EHV-1 infection.

PMID- 16881854
TI  - Effects of human recombinant alpha-2b interferon and feline recombinant omega
      interferon on in vitro replication of feline herpesvirus-1.
AB  - OBJECTIVE: To evaluate the effects of recombinant human interferon alpha-2b
      (rHuIFN-alpha2b) and recombinant feline interferon omega (rFeIFN-omega) on in
      vitro replication of feline herpesvirus (FHV)-1. SAMPLE POPULATION: Cultures of
      Crandell-Rees feline kidney (CRFK) cells. PROCEDURES: CRFK cells were treated
      with rFeIFN-omega or rHuIFN-alpha2b at concentrations ranging from 100 to 500,000
      U/mL. Cultures were then inoculated with FHV-1. Constant concentrations of
      interferon products were maintained throughout the study. Reductions in the
      number and size of plaques were used as indicators of antiviral activity. Six
      plaque reduction assays were performed in duplicate. A 3-(4, 5-dimethylthiazolyl
      2)-2, 5-diphenyltetrazolium bromide assay was used to detect cytotoxic effects of
      interferon. A 1-way ANOVA and Dunnett test were used to determine significant
      differences. RESULTS: Treatment with rFeIFN-omega at various concentrations
      resulted in significant reductions in the number of plaques (100,000 U/mL, 54.7%;
      and 500,000 U/mL, 59.8%) and in plaque size (100,000 U/mL, 47.5%; 250,000 U/mL,
      81.0%; and 500,000 U/mL; 70.5%). Treatment with various concentrations of rHuIFN
      alpha2b resulted in a significant reduction in plaque size (100,000 U/mL, 56.0%;
      250,000 U/mL, 75.7%; and 500,000 U/mL, 69.0%). None of the tested concentrations
      of interferon caused significant cellular toxicosis. CONCLUSIONS AND CLINICAL
      RELEVANCE: At some of the higher concentrations, the antiviral effect of rFeIFN
      omega was greater than the antiviral effect of rHuIFN-alpha2b. Reduction in
      plaque size appeared to be a good indicator of the antiviral activity of
      interferon against FHV-1.

PMID- 16881855
TI  - Transmission of bovine coronavirus and serologic responses in feedlot calves
      under field conditions.
AB  - OBJECTIVE: To compare shedding patterns and serologic responses to bovine
      coronavirus (BCV) in feedlot calves shipped from a single ranch in New Mexico (NM
      calves) versus calves assembled from local sale barns in Arkansas (AR calves) and
      to evaluate the role of BCV on disease and performance. ANIMALS: 103 feedlot
      calves from New Mexico and 100 from Arkansas. PROCEDURES: Calves were studied
      from before shipping to 35 days after arrival at the feedlot. Nasal swab
      specimens, fecal samples, and serum samples were obtained before shipping, at
      arrival, and periodically thereafter. Bovine coronavirus antigen and antibodies
      were detected by use of an ELISA. RESULTS: NM calves had a high geometric mean
      titer for BCV antibody at arrival (GMT, 1,928); only 2% shed BCV in nasal
      secretions and 1% in feces. In contrast, AR calves had low antibody titers
      against BCV at arrival (GMT, 102) and 64% shed BCV in nasal secretions and 65% in
      feces. Detection of BCV in nasal secretions preceded detection in feces before
      shipping AR calves, but at arrival, 73% of AR calves were shedding BCV in nasal
      secretions and feces. Bovine coronavirus infection was significantly associated
      with respiratory tract disease and decreased growth performance in AR calves.
      CONCLUSIONS AND CLINICAL RELEVANCE: Replication and shedding of BCV may start in
      the upper respiratory tract and spread to the gastrointestinal tract. Vaccination
      of calves against BCV before shipping to feedlots may provide protection against
      BCV infection and its effects with other pathogens in the induction of
      respiratory tract disease.

PMID- 16881856
TI  - Clinical, microbiological, and molecular characterization of methicillin
      resistant Staphylococcus aureus infections of cats.
AB  - OBJECTIVE: To compare clinical information obtained from medical records of cats
      with methicillin-resistant Staphylococcus aureus (MRSA) and methicillin
      susceptible S aureus (MSSA) infections, evaluate antibiograms of MRSA and MSSA
      for multiple-drug resistance (MDR), and characterize the strain type and
      staphylococcal chromosome cassette (SCC)mec type of each MRSA. SAMPLE POPULATION:
      70 S aureus isolates obtained from 46 cats. PROCEDURES: Clinical information
      obtained from medical records, including signalment, clinical signs, histologic
      examination of affected tissues, and outcomes, was compared between the 2 groups.
      Composite antibiograms of MRSA and MSSA were compared statistically. The MRSA
      strains were characterized by use of pulsed-field gel electrophoresis and SCCmec
      typing. RESULTS: No statistical differences in signalment or subjective
      differences in clinical signs or outcomes were detected between groups with MRSA
      or MSSA infection. Significant differences in antimicrobial resistance were
      detected, with MRSA having complete resistance to fluoroquinolone and macrolide
      antimicrobials, whereas MSSA maintained a high frequency of susceptibility. Seven
      pulsed-field patterns were observed in 15 MRSA strains; all but 1 were highly
      related. All MRSA isolates contained a type II SCCmec element. CONCLUSIONS AND
      CLINICAL RELEVANCE: Because MDR cannot be predicted in staphylococcal infections
      in cats on the basis of clinical signalment, culture and susceptibility testing
      are recommended whenever initial empirical treatment is unsuccessful. Molecular
      characterization of MRSA strains suggests that there has been reverse-zoonotic
      transmission from humans. IMPACT FOR HUMAN MEDICINE: The SCCmec type II element
      is typically associated with nosocomial MRSA infections of people. Cats may serve
      as reservoirs for MRSA infections in humans.

PMID- 16881857
TI  - Classification of Actinobacillus spp isolates from horses involved in mare
      reproductive loss syndrome.
AB  - OBJECTIVE: To identify Actinobacillus spp isolates recovered from fetuses and
      pericardial fluid from horses affected with mare reproductive loss syndrome
      (MRLS) and determine whether these bacterial species are the same as those
      isolated from clinically normal horses. SAMPLE POPULATION: Isolates of
      actinobacilli recovered from 18 horses with pericarditis and 109 fetuses aborted
      by mares affected by MRLS. Procedures-Actinobacillus spp isolates were identified
      to the level of species or subspecies by use of conventional phenotypic tests and
      biochemical and enzyme test kits. The 16S rRNA gene from selected isolates was
      amplified, purified, and sequenced. Sequence data were compared with sequence
      data for actinobacilli in GenBank. RESULTS: Of the 109 isolates obtained from
      fetuses, 14 were Actinobacillus equuli subsp equuli, 65 were A equuli subsp
      haemolyticus, 28 were Bisgaard taxon 10-like bacterium, and 2 were Actinobacillus
      genomospecies 1. Of the 18 isolates from horses with pericarditis, 4 were A
      equuli subsp equuli, 13 were A equuli subsp haemolyticus, and 1 was Bisgaard
      taxon 10-like bacterium. Comparisons with published data and GenBank data
      revealed that the isolates recovered from horses with MRLS were the same as those
      isolated from the oral cavity or alimentary tract of healthy horses. CONCLUSIONS
      AND CLINICAL RELEVANCE: Actinobacillus spp isolates recovered from fetuses and
      pericardial fluid samples of horses affected by MRLS in 2001 to 2003 were
      identical to Actinobacillus spp found in the oral cavity and alimentary tracts of
      healthy horses.

PMID- 16881858
TI  - Comparative analysis of cytokine gene expression in cerebrospinal fluid of horses
      without neurologic signs or with selected neurologic disorders.
AB  - OBJECTIVE: To determine gene transcription for cytokines in nucleated cells in
      CSF of horses without neurologic signs or with cervical stenotic myelopathy
      (CSM), West Nile virus (WNV) encephalitis, equine protozoal myeloencephalitis
      (EPM), or spinal cord trauma. ANIMALS: 41 horses (no neurologic signs [n = 12],
      CSM [8], WNV encephalitis [9], EPM [6], and spinal cord trauma [6]). PROCEDURES:
      Total RNA was extracted from nucleated cells and converted into cDNA. Gene
      expression was measured by use of real-time PCR assay and final quantitation via
      the comparative threshold cycle method. RESULTS: Cytokine genes expressed by
      nucleated cells of horses without neurologic signs comprised a balance between
      proinflammatory tumor necrosis factor-alpha (TNF-alpha), anti-inflammatory
      cytokines (interleukin [IL]-10 and transforming growth factor [TGF]-beta), and
      Th1 mediators (interferon [IFN]-gamma). Cells of horses with CSM mainly expressed
      genes for TNF-alpha, TGF-beta, and IL-10. Cells of horses with WNV encephalitis
      mainly expressed genes for IL-6 and TGF-beta. Cells of horses with EPM mainly had
      expression of genes for IL-6, IL-8, IL-10, TNF-alpha, IFN-gamma, and TGF-beta.
      Cells from horses with spinal cord trauma had expression mainly for IL-6; IFN
      gamma; TGF-beta; and less frequently, IL-2, IL-10, and TNF-alpha. Interleukin-8
      gene expression was only detected in CSF of horses with infectious diseases.
      CONCLUSIONS AND CLINICAL RELEVANCE: Despite the small number of CSF samples for
      each group, results suggest distinct gene signatures expressed by nucleated cells
      in the CSF of horses without neurologic signs versus horses with inflammatory or
      traumatic neurologic disorders.

PMID- 16881859
TI  - Assessment of the use of RNA quality metrics for the screening of articular
      cartilage specimens from clinically normal dogs and dogs with osteoarthritis.
AB  - OBJECTIVE: To assess 2 methods of RNA purification by use of different quality
      metrics and identify the most useful metric for quality assessment of RNA
      extracted from articular cartilage from dogs with osteoarthritis. SAMPLE
      POPULATION: 40 articular cartilage specimens from the femoral heads of 3
      clinically normal dogs and 37 dogs with osteoarthritis. PROCEDURES: RNA was
      extracted from articular cartilage by 2 purification methods. Quality metrics of
      each sample were determined and recorded by use of a UV spectrophotometer (Spec
      I; to determine the 260 to 280 nm absorbance ratio [A(260):A(280) ratio]), a
      second UV spectrophotometer (Spec II; to determine A(260):A(280) and
      A(260):A(230) absorbance ratios), and a microfluidic capillary electrophoresis
      analyzer (to determine the ribosomal peak ratio [RR], degradation factor [DF],
      and RNA integrity number [RIN]). The RNA was extracted from affected
      (osteoarthritic) articular cartilage and assessed with the same quality metrics.
      Metric results were compared with visual analysis of the electropherogram to
      determine the most useful RNA quality metric. RESULTS: No differences in methods
      of RNA purification were determined by use of quality metrics. The RNA extracted
      from unaffected (normal) cartilage was of higher quality than that extracted from
      affected (osteoarthritic) cartilage, as determined by the RIN and Spec II
      A(260):A(230) ratio. The RIN and RR were the most sensitive metrics for
      determining RNA quality, whereas the DF was most specific. A significant
      proportion (32%) of RNA extracted from osteoarthritic articular cartilage
      specimens was determined as being of low quality. CONCLUSIONS AND CLINICAL
      RELEVANCE: No single metric provided a completely sensitive and specific
      assessment of the quality of RNA recovered from articular cartilage.

PMID- 16881860
TI  - Vascular distribution of contrast medium during intraosseous regional perfusion
      of the distal portion of the equine forelimb.
AB  - OBJECTIVE: To describe the vascular distribution pattern of contrast medium
      during intraosseous regional perfusion (IORP) of the distal portion of the equine
      forelimb. SAMPLE POPULATION: 13 cadaveric forelimbs from 12 horses without
      forelimb diseases. PROCEDURES: Serial lateromedial radiographic views were taken
      of the distal portion of 10 heparinized cadaveric forelimbs at 0, 1, 2, 6, 15,
      and 30 minutes during IORP of the third metacarpal bone (MCIII) by use of
      iodinated contrast medium and a tourniquet placed over the proximal portion of
      MCIII. Vascular regions of interest (ROI) were created for each radiograph.
      Reviewers identified the presence or absence of contrast medium-induced opacified
      vessels in all ROI on radiographs. This information was summarized to identify
      vessel-filling patterns over time. Vessel identification was verified by use of
      computed tomography angiography and latex perfusion studies on the distal portion
      of separate cadaveric forelimbs. RESULTS: During IORP, contrast medium filled the
      medullary cavity of the MCIII; exited via transcortical vessels; and diffused
      distally to the remaining arteries and veins of the forelimb, distal to the
      tourniquet. Maximum vessel and soft tissue opacification occurred in most
      specimens at 6 and 30 minutes, respectively. Serial radiography vessel patterns
      matched those of computed tomography images and dissected specimens. CONCLUSIONS
      AND CLINICAL RELEVANCE: IORP provides a repeatable pattern of vascular
      distribution in the distal portion of the equine forelimb. To our knowledge, our
      study provides the first documentation of arterial perfusion by use of IORP;
      results of previous reports indicate that IORP delivers medications to only the
      venous vessels of the perfused forelimb.

PMID- 16881861
TI  - Evaluation of manufacturing variability, diffusion of filling solutions, and long
      term maintenance of occlusion in silicone hydraulic occluders.
AB  - OBJECTIVE: To evaluate manufacturing variability, diffusion of filling solutions,
      and maintenance of occlusion over time in 3 sizes of silicone hydraulic occluders
      (HOs). SAMPLE POPULATION: 2-, 5-, and 20-mm HOs (HO2, HO5, and HO20,
      respectively). PROCEDURES: Manufacturing variability was analyzed by comparing
      variation in internal luminal areas and filling volumes within each size group.
      Occluders were filled to 100% occlusion with air (n = 4), saline (0.9% NaCl)
      solution (4), or sodium hyaluronate (4) and submerged in simulated body fluid.
      Changes in luminal area and weight were recorded for 133 days to evaluate
      maintenance of occlusion. RESULTS: Considerable variability in uninflated luminal
      area and fill volumes was observed among the 3 sizes of HOs. Loss of occlusion
      developed in the first 12 hours in all air-filled HOs. Fluid-filled occluders
      were reliable in maintenance of occlusion after 133 days (99.99% for HO20, 99.59%
      for HO5, and 90.40% for HO2), although diffusion of saline solution and
      hyaluronate from all HOs was confirmed by detection of significant decreases in
      weight over time. There was no significant difference in weight loss between HOs
      filled with saline solution and HOs filled with sodium hyaluronate. CONCLUSIONS
      AND CLINICAL RELEVANCE: Saline solution or sodium hyaluronate may be used as a
      filling solution in the HOs tested. Maintenance of occlusion was best in the
      larger sizes. Saline solution or sodium hyaluronate should be used in future
      clinical investigations of HOs. Retrograde filling to remove air should be used
      when filling HOs with fluid.

PMID- 16881862
TI  - Not-so-sweet sixteen: the role of IL-16 in infectious and immune-mediated
      inflammatory diseases.
AB  - Over the past two decades, our understanding of interleukin-16 (IL-16) has
      increased substantially. Initial studies characterizing IL-16 as a chemotactic
      cytokine (but not a chemokine) just scratched the surface of the unique
      properties of this cytokine. Since then, scientists have determined that IL-16
      has a wide range of effects on cells, including upregulation of CD25, induction
      of cells to progress to the G(1) phase, inhibition of antigen- specific
      proliferation yet with retained antigen nonspecific proliferative properties, and
      discovery of a novel neuronal form with unique properties. Recently, a plethora
      of studies have implicated IL-16 in exacerbation of infectious, immune-mediated,
      and autoimmune inflammatory disorders, including atopic dermatitis, irritable
      bowel syndrome, systemic lupus erythematosus, neurodegenerative disorders, and
      viral infections. Herein, we review the body of evidence supporting a role for IL
      16 in infectious and immune-mediated inflammatory disorders and explore the known
      and possible mechanism of actions in the numerous diseases.

PMID- 16881863
TI  - c-Jun N-terminal kinase negatively regulates dsRNA and RSV induction of tumor
      necrosis factor- alpha transcription in human epithelial cells.
AB  - Secretion of inflammatory cytokines is the initial step of the immune response to
      viral infections. This innate immune response is mediated by the expression of a
      variety of cytokines, exemplified by tumor necrosis factor- alpha (TNF-alpha).
      The presence of dsRNA during viral infections is a key step in activation of
      several signaling pathways, including protein kinase R (PKR), toll-like receptor
      3 (TLR3), mitogen-activated protein kinase (MAPK), activator protein-1 (AP-1),
      interferon regulatory factors (IRFs), and NF-kappaB pathways, which are all
      relevant in the expression of inflammatory cytokines. We previously reported that
      PKR and p38 MAPK were required for dsRNA and viral induction of inflammatory
      cytokines in epithelial cells. Here, we report that activation of c-Jun N
      terminal kinase (JNK) during dsRNA treatment or respiratory syncytial viral (RSV)
      infection negatively regulates the induction of TNF-alpha in human epithelial
      cells. Inhibition of JNK by a pharmacologic inhibitor showed that expression of
      TNF-alpha increased following both dsRNA treatment and infection with RSV.
      Importantly, transfection of epithelial cells with a dominant-negative mutant of
      JNK significantly increased dsRNA induction of TNF-alpha. The mechanism by which
      JNK inhibition increases TNF-alpha induction appears to be through p38 MAPK
      activation. Our data show that JNK is a negative regulator of dsRNA and RSV
      induction of TNF-alpha expression and, thus, may act as a counterbalance to
      proinflammatory signals generated during viral infections.

PMID- 16881864
TI  - Functional annotation of IFN-alpha-stimulated gene expression profiles from
      sensitive and resistant renal cell carcinoma cell lines.
AB  - The antiproliferative, antiviral, and immunomodulatory properties of interferons
      (IFNs) have led to its therapeutic implementation. IFNs effects are mediated by a
      complex network of signal transducers, culminating in IFN-stimulated gene (ISG)
      induction. This complexity leads to diverse clinical responses to IFN, from no
      response to complete regression of disease. Elucidation of ISG induction patterns
      is, therefore, essential to understand and maximize its therapeutic potential. To
      correlate ISG expression profiles with IFN responsiveness, two renal cell
      carcinoma (RCC) cell lines differing in antiviral and apoptotic response to IFN
      were treated with IFN-alpha for different times, and expression profiles were
      analyzed using a customized microarray containing 850 unique putative ISGs. Genes
      with similar kinetics of induction in both cell lines were clustered and analyzed
      for gene function. Seven sets of coordinately regulated genes were identified by
      k-means cluster analysis, and significant functional similarities were identified
      for five of the seven sets. Strikingly, expression of genes associated with
      transcription temporally preceded expression of those involved in signal
      transduction. Enhanced antiviral sensitivity to IFN was coincident with sustained
      expression of ISGs involved in transcriptional regulation. However, no difference
      in Stat1 activation was observed between the cell lines. Analysis of ISG
      expression patterns suggests that subtle differences in transcription profiles
      contribute to differences in IFN responsiveness.

PMID- 16881865
TI  - Mycobacterium tuberculosis and Mycobacterium avium inhibit IFN- gamma -induced
      gene expression by TLR2-dependent and independent pathways.
AB  - Mycobacteria-infected macrophages are poor responders to interferon-gamma (IFN
      gamma), resulting in decreased expression of IFN-gamma-induced genes. In the
      present study, we examined the inhibition of IFN-gamma-induced gene expression by
      Mycobacterium tuberculosis and four different Mycobacterium avium strains in
      mouse RAW264.7 macrophages. Gamma-irradiated M. tuberculosis inhibited mRNA
      expression of a panel of six different IFN- gamma-induced genes. All four of the
      M. avium strains completely inhibited IFN-gamma-induced expression of MHC class
      II Aalpha and Ebeta mRNA. However, the Mac101 strain, which is serovar 1,
      inhibited IFN-gamma induction of IFN regulatory factor-1 (IRF-1) and guanylate
      binding protein-1 (GBP-1) mRNA to a greater extent than the other M. avium
      strains, which are serovar 2. In this study, we also show that mycobacteria
      inhibit gene expression by both toll-like receptor 2 (TLR2)-dependent and
      independent pathways. The inhibition of IFN-gamma-induced gene expression by M.
      avium was reduced but not completely blocked in macrophages from TLR2(/) mice.
      IFN-gamma-induced gene expression was also inhibited by mycobacteria in RAW264.7
      cells expressing dominantnegative TLR2 or myeloid differentiation factor 88
      (MyD88), further indicating the existence of a pathway independent of TLR2 and
      MyD88. These data suggest that mycobacteria inhibit IFN-gamma-induced gene
      expression by multiple pathways involving both TLR2 and non-TLR receptors.

PMID- 16881866
TI  - Interleukin-10 and Th2 cytokines differentially regulate osteopontin expression
      in human monocytes and dendritic cells.
AB  - Osteopontin (OPN) is a pleiotrophic phosphoprotein involved in homeostatic and
      pathophysiologic responses. It is known to be a chemotactic cytokine for
      dendritic cells (DCs), a critical cell type in both innate and adaptive immune
      responses. We report herein a contrasting role of interleukin-10 (IL-10) and Th2
      cytokines in the regulation of OPN expression in human monocytes and monocyte
      derived DCs (Mo-DCs). Our results showed first that the expression of OPN in
      monocytes and Mo-DCs was induced in a time-dependent and dose-dependent manner by
      IL-10 but was inhibited by IL-4 or IL-13. Further, the basal level of OPN
      expression was also inhibited by IL-4. This inhibitory effect of IL-4 was
      associated with a faster decay of OPN transcripts and a decreased proximal
      promoter activity of OPN in IL-4-treated cells. These results demonstrate a novel
      role of IL-10 and Th2 cytokines in the regulation of DC function through their
      contrasting regulatory activities on the expression of OPN.

PMID- 16881867
TI  - Influence of IFN- alpha and IFN- gamma on lymphangiogenesis.
AB  - Malignant cancers commonly spread by local invasion followed by metastasis
      through venous or lymphatic passages or both to distant sites. Angiogenesis and
      its relation to tumor growth and metastasis have been extensively researched. To
      date, however, the role played by lymphangiogenesis and metastasis of cancer has
      been overlooked. Inhibition of lymphangiogenesis, compared with inhibition of
      angiogenesis, may provide new insight to the mechanisms of metastasis of cancers.
      The current study was designed to examine the effect of two commonly used
      inhibitors of angiogenesis, interferon-alpha (IFN-alpha ) and IFN-gamma, on the
      growth and proliferation of lymphatic endothelial (LE) cells isolated from pig
      thoracic duct under in vitro condition. The LE cells were isolated and marked
      using specific markers, such as VEGFR-3 and LYVE-1, before experimental studies.
      The results showed that treatment of LE cells derived from the thoracic duct with
      these two inhibitors caused a decrease in the rate of cell proliferation in a
      dose-dependent manner, as assessed by MTT assays (tetrazolium salt colorimetric
      assay). Cell migration rate was assessed by the speed at which the cell migrated
      out from the scrape-wound margin; the speed of migration of LE cells was
      significantly inhibited in a dose-dependent fashion compared with controls.
      Treatment with both IFN-alpha and IFN-gamma caused an increase in apoptosis of LE
      cells, as assessed by Hoechst staining and caspase-3 staining. Our results showed
      that both IFN-alpha and IFN-gamma were able to inhibit LE cell growth in a dose
      dependent manner and that the inhibition may be through induction of apoptosis of
      endothelial cells.

PMID- 16881868
TI  - Anti-inflammatory activity of a pteridine derivative (4AZA2096) alleviates TNBS
      induced colitis in mice.
AB  - Elevated production of tumor necrosis factor (TNF) plays a central role in the
      pathogenesis of many inflammatory diseases, such as rheumatoid arthritis and
      Crohn's disease. Naturally occurring pteridine analogs have been reported to have
      potent immunomodulatory activity, especially on TNF production. The aim of this
      study is to identify small molecule TNF inhibitiors derived from pteridine and to
      prove their in vivo efficacy in an inflammatory model. A focused chemical library
      based on the pteridine scaffold was screened in vitro on lipopolysaccharide (LPS)
      induced TNF production in peripheral blood mononuclear cells (PBMC). One
      synthetic pteridine analog (4AZA2096), shown to have strong inhibitory activity,
      was selected and tested for its efficacy to treat trinitrobenzenesulfonate (TNBS)
      induced colitis in mice, a model of Crohn's disease. Colitis was induced by
      rectal administration of 1 mg TNBS in 50% ethanol after presensitization via the
      skin. The synthetic pteridine analog 4AZA2096 was shown to potently inhibit LPS
      induced TNF production in vitro. Colitic mice treated with 4AZA2096 orally (20
      mg/kg/day) recovered more rapidly and, histologically, had a reduction of
      inflammatory lesions, less edema, a reduction of goblet cell loss, and reduced
      wall thickness. Cell infiltration in the colon, especially infiltration of
      neutrophils, as shown by myeloperoxidase (MPO) activity, was reduced in 4AZA2096
      treated animals. Intralesional TNF production was lower in mice of the treated
      groups, whereas interleukin-18 (IL-18) and interferon-gamma (IFN-gamma) mRNA were
      not affected. Treatment had no effect on anti-TNBS antibody production, arguing
      against generalized immunosuppression. In conclusion, we identified a pteridine
      derivative, 4AZA2096, with strong inhibitory activity on TNF production and a
      remission- inducing effect in TNBS colitis, supporting further preclinical and
      clinical development of this novel TNF inhibitor for treatment of inflammatory
      diseases.

PMID- 16881871
TI  - Pyrrolidine dithiocarbamate protects the small bowel from warm
      ischaemia/reperfusion injury of the intestine: the role of haem oxygenase.
AB  - IR (ischaemia/reperfusion) injury of the intestine occurs commonly during
      abdominal surgery. We have previously shown that PDTC (pyrrolidine
      dithiocarbamate), an HO-1 (haem oxygenase-1) donor, improves intestinal
      microvascular perfusion. In the present study, we have investigated the effects
      of PDTC on the intestinal microcirculation following IR (ischaemia/reperfusion)
      injury of the intestine. Male Sprague-Dawley rats (n=72) were randomly assigned
      to four groups (n=18/group): (i) sham-operated group, who underwent laparotomy
      without induction of IR of the intestine; (ii) IR group, who were subjected to 30
      min of superior mesenteric artery occlusion and 2 h of reperfusion; (iii) PDTC+IR
      group, who received PDTC prior to IR; and (iv) ZnPP group, who received the HO-1
      inhibitor ZnPP (zinc protoporphyrin) followed by procedures as in group (iii).
      The ileum was evaluated for changes in tissue cytochrome c oxidase redox status,
      RBC (red blood cell) dynamics and leucocyte-endothelial interactions. The
      expression of HO-1 in the ileal tissue was examined at the end of the
      reperfusion. PDTC significantly improved the intestinal tissue oxygenation,
      mucosal perfusion index and RBC velocity compared with the IR and ZnPP groups.
      PDTC also decreased the leucocyte-endothelial interactions (P<0.05 compared with
      the IR and ZnPP groups). PDTC induced the expression of HO-1, whereas ZnPP
      abolished this effect.

PMID- 16881870
TI  - Ovine plasma prion protein levels show genotypic variation detected by C-terminal
      epitopes not exposed in cell-surface PrPC.
AB  - Ovine PBMCs (peripheral blood mononuclear cells) express PrP(C) [cellular PrP
      (prion-related protein)] and have the potential to harbour and release disease
      associated forms of PrP during scrapie in sheep. Cell-surface PrP(C) expression
      by PBMCs, together with plasma PrP(C) levels, may contribute to the regulatory
      mechanisms that determine susceptibility and resistance to natural scrapie in
      sheep. Here, we have correlated cell-surface PrP(C) expression on normal ovine
      PBMCs by FACS with the presence of PrP(C) in plasma measured by capture-detector
      immunoassay. FACS showed similar levels of cell-surface PrP(C) on homozygous ARR
      (Ala136-Arg154-Arg171), ARQ (Ala136-Arg154-Gln171) and VRQ (Val136-Arg154-Gln171)
      PBMCs. Cell-surface ovine PrP(C) showed modulation of N-terminal epitopes, which
      was more evident on homozygous ARR cells. Ovine plasma PrP(C) levels showed
      genotypic variation and the protein displayed C-terminal epitopes not available
      in cell-surface PrP(C). Homozygous VRQ sheep showed the highest plasma PrP(C)
      level and homozygous ARR animals the lowest. For comparison, similar analyses
      were performed on normal bovine PBMCs and plasma. PrP(C) levels in bovine plasma
      were approx. 4-fold higher than ovine homozygous ARQ plasma despite similar
      levels of PBMC cell-surface PrP(C) expression. Immunoassays using C-terminal
      specific anti-PrP monoclonal antibodies as capture and detector reagents revealed
      the highest level of PrP(C) in both ovine and bovine plasma, whilst lower levels
      were detected using N-terminal-specific monoclonal antibody FH11 as the capture
      reagent. This suggested that a proportion of plasma PrP(C) was N-terminally
      truncated. Our results indicate that the increased susceptibility to natural
      scrapie displayed by homozygous VRQ sheep correlates with a higher level of
      plasma PrP(C).

PMID- 16881874
TI  - Sociocultural influences on infant feeding decisions among HIV-infected women in
      rural Kwa-Zulu Natal, South Africa.
AB  - The promotion of exclusive breastfeeding for 6 months, followed by rapid
      transition to alternative food sources may be an important public health approach
      to the reduction of mother-to-child transmission of HIV through breastmilk. The
      basic ethical principle of 'informed choice' requires that HIV positive women are
      provided with adequate information about their options. However, information is
      only one factor that affects their decisions. The objective of this ethnographic
      study was to identify sociocultural influences on infant feeding decisions in the
      context of a large cohort study designed to assess the impact of a breastfeeding
      counselling and support strategy to promote exclusive breastfeeding on postnatal
      transmission of HIV in African women. Following an initial period of exploratory
      interviewing, ethnographic techniques were used to interview 22 HIV positive
      women about their views on infant feeding and health. Interviews were tape
      recorded, transcribed and analysed with a text analysis program. Five themes of
      influences on feeding decisions emerged: (1) social stigma of HIV infection; (2)
      maternal age and family influences on feeding practices; (3) economic
      circumstances; (4) beliefs about HIV transmission through breastmilk; and (5)
      beliefs about the quality of breastmilk compared to formula. The study highlights
      the role of cultural, social, economic and psychological factors that affect HIV
      positive women's infant feeding decisions and behaviour.

PMID- 16881872
TI  - Protein 4.1R self-association: identification of the binding domain.
AB  - Erythroid protein 4.1 (4.1R) stabilizes the spectrin-actin network and anchors it
      to the plasma membrane. To contribute to the characterization of non-erythroid
      protein 4.1R, we used sedimentation, pull-down and co-immunoprecipitation assays
      to investigate the ability of protein 4.1R to establish inter-/intra-molecular
      associations. We demonstrated that the small 4.1R isoforms of 60 kDa (4.1R60),
      but not the larger isoforms of 80 and 135 kDa (4.1R80 and 4.1R135), were self
      associated, and that a domain contained in all 4.1R isoforms, the core region,
      was responsible for 4.1R self-association. Results from denaturing-renaturing
      experiments, in which an initially non-self-associated 4.1R80 isoform became self
      associated, suggested that an initially hidden core region was subsequently
      exposed. This hypothesis was supported by results from pull-down assays, which
      showed that the core region interacted with the N-terminal end of the FERM (4.1,
      ezrin, radixin, moesin) domain that is present in 4.1R80 and 4.1R135 isoforms but
      absent from 4.1R60 isoforms. Consistently, 4.1R80 isoforms bound neither to each
      other nor to 4.1R60 isoforms. We propose that 4.1R60 isoforms are constitutively
      self-associated, whereas 4.1R80 and 4.1R135 self-association is prevented by
      intramolecular interactions.

PMID- 16881875
TI  - Infant weight-for-length is positively associated with subsequent linear growth
      across four different populations.
AB  - Several studies have documented that length gain often lags behind weight gain
      during infancy and early childhood, suggesting that linear growth is partly
      regulated by initial body mass or fatness. To investigate this hypothesis, we
      analysed data from four longitudinal studies on growth of infants in the first 12
      months: (1) U.S. breast-fed and formula-fed infants (n = 89); (2) breast-fed
      infants in Ghana (n = 190); (3) normal birthweight, breast-fed infants in
      Honduras (n = 108); and (4) term, low-birthweight breast-fed infants in Honduras
      (n = 119). The dependent variable was length gain during each 3-month interval (1
      4, 2-5, 3-6, 4-7, 5-8, 6-9, 7-10, 8-11 and 9-12 months). Three main independent
      variables were examined: initial weight-for-length z-score (W/L), weight change
      during the prior 3 months, and initial skinfold thickness. Controlling for
      maternal height, infant sex, and initial length-for-age z-score, length gain was
      positively correlated with initial W/L and prior weight change during all age
      intervals and with initial skinfold thickness at 3 and 4 months (r = 0.15-0.36; P
      < 0.01). There was no evidence of a threshold effect. These associations were
      evident in all four populations, in both boys and girls, and in breast-fed and
      formula-fed infants. The consistency of this relationship across studies supports
      the hypothesis that linear growth is partly regulated by initial body mass or
      fatness in infants.

PMID- 16881876
TI  - Government funded breastfeeding peer support projects: implications for practice.
AB  - In 1999, the Government, Department of Health in England, UK established the
      Infant Feeding Initiative. As part of this initiative, 79 1-year infant feeding
      projects were selected for funding. The funded projects specifically centred upon
      practice innovation and evaluation in relation to promoting breastfeeding and
      supporting breastfeeding women in socially excluded communities. The DH recently
      commissioned a comprehensive evaluation of the 79 projects (DH 2003). This paper
      focuses upon the evaluation of the 26 DH funded projects that specifically
      focused upon breastfeeding peer support schemes. The evaluation illuminated many
      of the challenges involved in implementing community based breastfeeding peer
      support schemes. Lessons learnt from the most effective projects in terms of:
      potential to increase breastfeeding initiation and continuation rates; uptake of
      the service; comprehensive evaluation; and sustainability are presented here, as
      a series of steps required for successful operationalization of breastfeeding
      peer support schemes. When these steps are followed, peer support schemes offer
      exciting prospects for supporting breastfeeding women and increasing
      breastfeeding initiation and continuation rates, while respecting diversity,
      ensuring inclusivity and stimulating community empowerment.

PMID- 16881877
TI  - Evaluation of the use of health care assistants to support disadvantaged women
      breastfeeding in the community.
AB  - There is little experience of the use of health care assistants in the community
      to support breastfeeding in the UK. The aim of this project was to evaluate the
      implementation of a small-scale pilot project using health care assistants in the
      community to support disadvantaged women breastfeeding. The evaluation was funded
      as part of the Department of Health's Infant Feeding Initiative. A longitudinal
      observational and quasi-experimental design was used. The project involved women,
      who had recently given birth, living in an area of London identified by the
      government's Sure Start scheme as socio-economically disadvantaged. This paper
      focuses mainly on the findings drawn from the qualitative data focusing on the
      process of implementation, the role of the Support Worker and women's perceptions
      of the support. The findings suggest that the use of health care assistants in
      the community may offer a practical and encouraging approach in supporting
      breastfeeding which is acceptable to both breastfeeding women and health care
      professionals. More research is needed to establish whether the intervention
      significantly increases breastfeeding rates.

PMID- 16881878
TI  - Enterobacter sakazakii and other bacteria in powdered infant milk formula.
AB  - Recently there has been considerable concern related to the presence of bacteria,
      in particular Enterobacter sakazakii, in powdered infant formula milk. This paper
      considers the bacteria in these products at point of sale, with reference to
      current microbiological testing and the need for good hygienic practice in their
      subsequent preparation before feeding. The ingestion of raised numbers of E.
      sakazakii resulting from temperature abuse after reconstitution is highlighted as
      well as the uncertain routes of E. sakazakii product contamination.

PMID- 16881879
TI  - Linking traditional treatments of maternal anaemia to iron supplement use: an
      ethnographic case study from Pemba Island, Zanzibar.
AB  - Iron deficiency anaemia is the most common form of malnutrition in the world.
      Pregnant women are particularly at risk for anaemia. Insufficient attention has
      been paid to the reasons underlying the only moderate success of iron
      supplementation. In this article an additional factor that can affect the use of
      iron supplements is proposed: their relevance to 'traditional' or nonbiomedical
      treatments of anaemia. This paper represents what is to our knowledge the first
      ethnographic description of nonbiomedical treatments for maternal anaemia. The
      research was conducted over several months on Pemba, one of the islands of the
      Zanzibar archipelago. Data were collected using a variety of qualitative methods,
      including in-depth interviews, focus group discussions and participant
      observation. Informants included 25 mothers and 27 traditional and biomedical
      health care workers. The resulting ethnography elucidates Pembans' beliefs about
      the relationship of food, traditional medicine, spirits and biomedical medicine
      in relation to anaemia. In the analysis of the ethnography, both anthropology and
      public health perspectives are incorporated to suggest how the understanding of
      these beliefs is useful for increasing iron supplement use.

PMID- 16881881
TI  - Neonatal nutrition: the long road travelled only partially so.

PMID- 16881882
TI  - Weight monitoring of breastfed babies in the UK - centile charts, scales and
      weighing frequency.
AB  - Weighing infants during their first 6 months is an important focus of growth
      monitoring and a common activity of child health care services worldwide. In
      these same months, health workers provide support for breastfeeding and promote
      continued exclusive breastfeeding. The literature on the practice of weighing
      breastfed babies is reviewed, as it applies to the United Kingdom. The shape of
      the growth curves for breastfed babies differs from that of formula-fed infants
      and also from centile charts previously in use. The World Health Organization
      commitment to the production of a new growth reference has generated discussion
      of the implications of charts in use. The country-specific charts in use in the
      UK are examined and the data used to construct them discussed with reference to
      clinical use for breastfed infants. Recent UK discussions on charts, as well as
      on the frequency of routine weighing for babies in the community are considered,
      and the available evidence on the accuracy of weighing in practice is noted. The
      choices made in constructing different charts; the physical condition of scales
      and their use in practice have implications for plotted growth. This paper aims
      to present a wide range of evidence available in this area in order to encourage
      debate on practice. A companion paper will discuss issues of interpretation,
      conveying information to parents, and interventions.

PMID- 16881883
TI  - A weight gain chart for pregnant women designed in Chile.
AB  - The weight gain chart for pregnant women, developed by Rosso and Mardones (RM
      chart, 1997), is analysed and compared with other charts in terms of its
      usefulness for targeting nutritional interventions aimed at preventing low or
      high birth weights. The RM chart defines categories of maternal nutritional
      status in early gestation based on weight/height, expressed either as percentage
      of standard weight (PSW) or body mass index (BMI), and desirable gestational
      weight gains for each of these categories. Weight gain recommendations of the RM
      chart are proportional to maternal height. For underweight women the weight
      recommendation was derived from actual data, while for overweight and obese women
      it is based on data extrapolations. Since 1987 the Chilean National Health
      Service has used the RM chart as a standard in prenatal care in all its clinics,
      covering approximately 70% of the country's population, mostly middle and low
      income women. During the 1987-2001 period the proportion of underweight pregnant
      women and infants with birth weight < 3000 g decreased significantly and
      proportionally. Nevertheless, the proportion of obese pregnant women and infants
      with birth weight > or = 4000 g increased during this period. Multifactorial
      social changes including a decade of substantial economic growth in the country
      with improved family income, precludes the possibility of determining the
      efficacy of the RM chart in this group. However, the widespread use of the RM
      chart indicates that it is a helpful and easy-to-use instrument in the field.
      Further, by its clear graphical presentation of maternal nutritional status it
      helps draw the attention of health personnel to women who need special
      nutritional advice and support.

PMID- 16881884
TI  - The nutrient intakes of mothers of low birth weight babies - a comparison of
      ethnic groups in East London, UK.
AB  - The objective of this paper was to compare the nutrient intakes of mothers of
      different ethnic origins after they had given birth to a low birth weight (LBW)
      baby (< 2.5 kg). A total of 165 participants from East London, UK completed a
      prospective 7-day diet diary using household measures, between 8 and 12 weeks
      post-partum. The data were originally collected as baseline data prior to two
      separate nutrition intervention studies and were combined and re-interrogated for
      the purpose of this paper. Folate and iron intakes were low in all ethnic groups
      compared to the Reference Nutrient Intakes (RNI). Half did not meet the RNI for
      folate and 88% did not meet the RNI for iron. Nearly a quarter of the group did
      not achieve the Lower Reference Nutrient Intake (LRNI) for iron. The mean vitamin
      D and calcium intakes were significantly different between the ethnic groups (P =
      0.007, P = 0.001, respectively). African women had the highest vitamin D intakes
      (4.72 microg d(-1)) and Caucasians and Asians the lowest (2.4 microg d(-1)).
      Caucasians had the highest calcium intakes (780 mg d(-1)) and Africans the lowest
      (565 mg d(-1)). Over two-thirds of African, Asian and African-Caribbean women did
      not meet the RNI for calcium. Thirty-one per cent of Africans did not meet the
      LRNI for calcium. Our data show a high prevalence of inadequate nutrition among
      women who deliver LBW babies with differences in nutrient intake between ethnic
      groups. This information can be used to target specific appropriate dietary
      advice to ethnic minorities for the prevention or repetition of LBW.

PMID- 16881885
TI  - Maternal nutritional knowledge and child nutritional status in the Volta region
      of Ghana.
AB  - The relationship between mother's nutritional knowledge, maternal education, and
      child nutritional status (weight-for-age) was the subject of investigation in
      this study. The data were collected in Ghana on 55 well nourished and 55
      malnourished mother-child pairs. A questionnaire designed to collect data on
      mother's knowledge and practices related to child care and nutrition was
      administered to the mothers. Data on mother's demographic and socio-economic
      characteristics as well as child anthropometric data were also collected. A
      nutrition knowledge score was calculated based on mother's responses to the
      nutrition related items. Bivariate analysis gave significant associations between
      child nutritional status and the following variables: time of initiating of
      breastfeeding, mother's knowledge of importance of colostrum and whether
      colostrum was given to child, age of introduction of supplementary food, and
      mother's knowledge about causes of kwashiorkor. The two groups also showed
      significant differences in their nutrition knowledge scores. Maternal formal
      education, and marital status were also found to be associated with child
      nutritional status in bivariate analyses. Further analysis with logistic
      regression revealed that maternal nutrition knowledge was independently
      associated with nutritional status after the effects of other significant
      variables were controlled for. Maternal education on the other hand was not found
      to be independently associated with nutritional status. These results imply that
      mother's practical knowledge about nutrition may be more important than formal
      maternal education for child nutrition outcome.

PMID- 16881886
TI  - Breastfeeding peer supporters and a community support group: evaluating their
      effectiveness.
AB  - Peer support for breastfeeding mothers has often been promoted as a way of
      increasing rates in communities with low breastfeeding prevalence, where there
      are few breastfeeding role models and a bottle-feeding culture predominates. This
      study evaluated the effectiveness of a peer support initiative, which trained
      peer supporters who then set up a support group, in an area of social and
      economic deprivation in South Bristol, UK. The effects of training on 6 local
      women were explored; the combined effect of peer support and the group on
      breastfeeding prevalence assessed; and mothers' views on what they had gained
      from the breastfeeding support group reported. Focus groups were held with the
      peer supporters, who also completed questionnaires before and after their
      training. Questionnaires were sent to all mothers (35) who attended the support
      group over the first 5 months to ascertain their views. Breastfeeding rates were
      extracted from routinely collected sources for both the local area and the wider
      Bristol population (excluding the peer support area). The initial training
      increased the peer supporters' knowledge about breastfeeding and their confidence
      in talking to and supporting mothers. The number of mothers attending the
      breastfeeding support group increased from 3 per week in May to 10 per week by
      September 2001. Mothers who attended the group particularly appreciated being
      able to talk about breastfeeding and getting consistent breastfeeding advice.
      Breastfeeding rates in the area for 12-months before and after the start of the
      peer support initiative showed a significant increase at 8 weeks (7%), which was
      higher than the overall increase in the wider Bristol area (3%). This evaluation
      suggests that peer supporters combined with a breastfeeding support group are an
      effective way of increasing breastfeeding prevalence in areas of low
      continuation.

PMID- 16881887
TI  - National collaborating centres for maternal and child nutrition.

PMID- 16881888
TI  - The pan European approach to breastfeeding.

PMID- 16881890
TI  - Early nutritional influences on obesity, diabetes and cardiovascular disease
      risk. Proceedings of an international workshop, Montreal, Canada, June 6-9, 2004.

PMID- 16881891
TI  - Early nutritional influences on obesity, diabetes and cardiovascular disease
      risk. International Workshop, Universite de Montreal, June 6-9, 2004.

PMID- 16881892
TI  - The developmental origins of adult disease.
AB  - Epidemiological and clinical observations have led to the hypothesis that the
      risk of developing some chronic diseases in adulthood is influenced not only by
      genetic and adult lifestyle factors, but also by environmental factors acting in
      early life. These factors act through the processes of developmental plasticity
      and possibly epigenetic modification, and can be distinguished from developmental
      disruption. The concept of predictive adaptation has been developed to explain
      the relationship between early life events and the risk of later disease. At its
      base, the model suggests that a mismatch between fetal expectation of its
      postnatal environment and actual postnatal environment contribute to later adult
      disease risk. This mismatch is exacerbated, in part, by the phenomenon of
      "maternal constraint" on fetal growth, which implicitly provides an upper limit
      of postnatal nutritional environment that humans have adapted for and is now
      frequently exceeded. These experimental, clinical and conceptual considerations
      have important implications for prevention and intervention in the current
      epidemic of childhood obesity and adult metabolic and cardiovascular disorders.

PMID- 16881893
TI  - Animal models of programming: early life influences on appetite and feeding
      behaviour.
AB  - Epidemiological observations of associations between early life nutrition and
      long-term disease risk have prompted detailed experimental investigation of the
      biological basis of programming. Studies using rodent or large animal models have
      clearly established the biological plausibility of nutritional programming and
      are now yielding important information on underlying mechanisms. Nutritional
      interventions in pregnancy, including global food restriction, protein
      restriction, micronutrient restriction and excess fat feeding, determine a
      consistent cluster of disorders in the resulting offspring. The common
      association of such diverse nutritional disturbances with hypertension, glucose
      intolerance and adiposity suggests that a small number of simple common
      mechanisms are active in response to fetal nutrient imbalance. Studies of rodent
      models indicate that fetal undernutrition determines adult adiposity. It is
      unclear whether the increase in central adiposity is related to increased food
      intake or reduced energy expenditure, although evidence exists to suggest that
      both may act together. Rats subject to intrauterine protein restriction exhibit
      increased preference for high fat foods. Feeding of energy dense foods to rats
      that were undernourished in utero promotes a greater degree of obesity than is
      noted in animals subject to adequate nutrition in fetal life. There is evidence
      to suggest that programming of appetite may stem from remodelling of hypothalamic
      structures that control feeding and programming of the expression of genes
      involved in responses to orexogenic hormones. The early life programming of
      appetite and obesity is a complex phenomenon and our understanding of how
      maternal nutrition determines later energy balance is at a very early stage.

PMID- 16881894
TI  - Early growth and adult health outcomes--lessons learned from the Helsinki Birth
      Cohort Study.
AB  - Slow growth during fetal life and infancy is often followed by accelerated weight
      gain in childhood. These patterns of growth seem to precede the development of
      coronary heart disease (CHD) and type 2 diabetes in adult life. Patterns of
      growth associated with CHD and type 2 diabetes in adult life are described based
      upon findings from the Helsinki Birth Cohort Study. We are beginning to
      understand that adult degenerative diseases are associated with different
      patterns of early growth. Yet it is not clear what optimal growth is and how it
      can be achieved. Most data suggest that the development of many non-communicable
      diseases involve a number of interactions including genetic ones. Therefore these
      diseases can best be focused upon from a life cycle perspective.

PMID- 16881895
TI  - Association between chronic undernutrition and hypertension.
AB  - In developing countries nutritional deficit during prenatal and continuing in
      post-natal life is very common. This condition leads to stunting and important
      metabolic changes. Over 30% of children in the world are stunted. The metabolic
      resultants of nutritional deficit during growth are classically known to aim at
      energy conservation. This review summarizes data from Brazil, a developing
      country undergoing the double burden of obesity and undernutrition, especially
      among the poor, and suggests that stunting or chronic undernutrition increases
      the risk of obesity and hypertension later in life. Around 60 million people are
      under the poverty line in Brazil. In Sao Paulo, the richest city of the country,
      20% of the population live in slums and in Maceio, the capital of one of the
      poorest states, this percentage reaches 50%. Undernutrition in this population is
      around 20% among children, with high frequency of infections, anemia, and
      parasitic infestations, associated with poor sanitation. Among stunted
      adolescents, we found a high prevalence of hypertension (21%) that is a
      considerably higher estimate compared to non-stunted adolescents (less than 10%).
      The prevalence of hypertension in undernourished pre-school children, or in those
      who recovered from undernutrition, was higher than that in controls (29%, 20% and
      2%, respectively, P < 0.001). Among stunted adults eating no more than 66% of the
      requirements (adjusted for stature), overweight/obesity was 35% in women and 25%
      in men. The prevalence of hypertension was 44% among stunted women and 18% among
      stunted men. Fifty per cent of stunted and obese women had hypertension. These
      data reinforce the important association between undernutrition and hypertension
      from childhood through adulthood. Health policies for preventing and combating
      childhood undernutrition should have an impact on the morbidity and mortality
      related to hypertension during adulthood.

PMID- 16881896
TI  - Infant and child feeding practices and childhood overweight: the role of
      restriction.
AB  - This review addresses the association between restrictive feeding practices by
      parents and the development of overweight in children. To date, only one parent
      feeding domain--feeding restriction--has been consistently linked to variations
      in child eating patterns or weight status. Despite challenges to unravelling
      causal pathways, the most current data suggest that restrictive feeding practices
      are elicited by child characteristics (e.g. weight status or obesity risk) and
      depend on parent characteristics as well. Restriction, in turn, may maintain or
      exacerbate child overweight. There remain important questions to be addressed in
      this literature, pertinent both to the development of childhood overweight and
      clinically to overweight prevention. Two areas of importance are the roles of
      cultural differences, as well as genes that confer risk for overweight, on the
      relationship between restriction and child weight status.

PMID- 16881897
TI  - Early growth and chronic disease: a public health overview.
AB  - Infant and childhood growth result from and reflect a range of influences in pre-
      and postnatal life. These include nutrition, burden of infection and the psycho
      social environment. Nutrition in young children is dependent on individual level
      factors such as fetal experience, infant feeding and weaning practices, and on
      societal factors such as education of women and economic conditions. The
      relationship of early postnatal growth to adult disease may be indicative or
      causal, and may reveal both biological and sociological processes. Although non
      insulin-dependent diabetes mellitus (NIDDM) and obesity are risk factors for
      ischaemic heart disease, the relationships of these three conditions to infant
      growth differ. Poor infant growth has been associated with higher levels of NIDDM
      and ischaemic heart disease, but lower levels of adult obesity. Most research has
      been of populations living in developed countries at different stages of
      nutritional transition. However, differences in context are not simply limited to
      the stage of the nutritional transition. They also need to consider the nature of
      that transition and its social correlates, which may result in the clustering of
      aetiological influences such as increased body mass and poverty. The size of
      effect of the relationship of infant growth to adult disease is important not
      only to determine its relative aetiological importance but also for its potential
      for public health policy. Such policy also needs to consider the relationships of
      infant growth to a range of outcomes, both health and human capital, which are
      not the subject of this workshop.

PMID- 16881899
TI  - The coexistence of child undernutrition and maternal overweight: prevalence,
      hypotheses, and programme and policy implications.
AB  - The purpose of this paper is to document the prevalence of the phenomenon of the
      coexistence of a stunted child and an overweight mother (SCOWT) in the same
      household in low- and middle-income countries. We also explore whether this
      phenomenon is associated with a country's level of economic development and
      urbanization and highlight policy directions for public nutrition. Data from 36
      Demographic and Health Surveys (DHS) were used (23 in Africa, 8 in Latin America,
      and 5 in Asia). Stunting was defined as height-for-age < -2 SD of the reference
      population and maternal overweight as a body mass index (BMI) of > 25 kg m(-2).
      World Bank and United Nations figures were used for gross national product per
      capita (an indicator of economic development) and for level of urbanization
      respectively. Descriptive statistics were derived, and multivariate linear
      regression analysis was used to model the association between economic
      development, urbanization and the prevalence of SCOWT. The prevalence of SCOWT is
      generally below 10%, except in four countries, of which three are in Latin
      America. Among our sample of countries, SCOWT is generally more prevalent in
      Latin America than in Africa, and is near or below 5% in all five countries of
      Asia. Contrary to our expectations, SCOWT is not necessarily more prevalent in
      urban than rural areas. We also find that when economic development is controlled
      for, SCOWT is associated with urbanization only in Latin America. In Africa and
      Asia, SCOWT is associated with economic development, but not urbanization. The
      concrete recognition of the SCOWT phenomenon is an important step to delineating
      more effective and integrated strategies to address problems of over- and
      undernutrition and dietary quality within countries, regions and households. This
      gives special importance to designing programmes and policies that will address
      the food and nutrition needs of each individual, rather than assuming that those
      needs are addressed by targeting programmes or policies to the household as a
      whole.

PMID- 16881898
TI  - Childhood growth and chronic disease: evidence from countries undergoing the
      nutrition transition.
AB  - Evidence is accumulating that the pattern of growth in childhood is associated
      with development of cardiovascular disease in adulthood, but such evidence comes
      mostly from developed countries. We conducted a review of studies from countries
      undergoing the nutrition transition. Five birth cohorts with measures of child
      growth and outcomes through adolescence were identified, from China, India,
      Guatemala, Brazil and the Philippines. Across studies there are major differences
      in data availability and in statistical approaches to modelling child growth and
      its effects. Nevertheless, generally consistent associations of growth failure in
      early childhood and development of overweight in later childhood with the risk of
      elevated blood pressure, glucose, and serum lipids in adulthood were observed. As
      these cohorts mature they will provide a wealth of critical information on the
      relation between early life factors and later disease risk, and efforts should be
      made to ensure ongoing follow-up using standardized approaches and more
      comprehensive assessments.

PMID- 16881901
TI  - Programme and policy issues related to promoting positive early nutritional
      influences to prevent obesity, diabetes and cardiovascular disease in later life:
      a developing countries view.
AB  - Public health policy differs from programme insofar as the former is the
      expression of goals at a higher decision-making level (international, regional,
      national or provincial) and the latter involves the execution of intervention
      measures at the community or individual level. It has recently become fashionable
      to speak of "evidence-based" policy. There is now ample evidence to suggest that
      early nutritional influences on chronic disease risk in later life are
      contributing to the acceleration of the overall worldwide epidemic of obesity and
      non-transmissible diseases. In developing countries, in which 80% of the world's
      population resides, the opportunities for preventive policy must be balanced
      against needs, cost and effectiveness considerations and the intrinsic
      limitations of policy execution. Not everyone in the population is at risk of
      suffering from any given negative condition of interest, nor will everyone at
      risk benefit from any given intervention. Hence, decisions must be made between
      universal or targeted policies, seeking maximal cost-efficiency, but without
      sowing the seeds of either discrimination or stigmatization with a non-universal
      application of benefits. Moreover, although large segments of the covered
      population may benefit from a public health measure, it may produce adverse and
      harmful effects on another segment. It is ethically incumbent on policy makers to
      minimize unintended consequences of public health measures. With respect to the
      particular case of mothers, fetuses and infants and long-term health, only a
      limited number of processes are amenable to intervention measures that could be
      codified in policy and executed as programmes.

PMID- 16881900
TI  - The policy challenge of coexisting undernutrition and nutrition-related chronic
      diseases.
AB  - The original focus on energy and protein needs for combating malnutrition gave
      way to UNICEF promoted concerns for maternal care and complementary feeding in
      association with longer-term breast feeding. Nevertheless the World Food Summit's
      drive to halve malnutrition rates by 2015 was not accelerating the fall in
      malnutrition prevalences. The UN's Standing Committee on Nutrition's commission
      highlighted the crucial role of maternal nutrition and low birthweights, the need
      for a life cycle approach to prevention and the current global effects of
      maternal/fetal and childhood malnutrition in amplifying the impact of the new
      epidemic of obesity and chronic diseases. The emphasis on poverty reduction and
      free market solutions is too crude and national interventions geared to
      protecting the vulnerable, promoting equity with major community involvement in
      integrated multifaceted programmes are needed. The same principles apply to
      overnutrition and specifically to the avoidance of the current pandemic of the
      metabolic syndrome. An intergenerational amplification of diabesity is now
      emerging as overweight but poorly fed micronutrient deficient girls enter
      pregnancy and produce ever more susceptible children. So new strategies are now
      needed as recognized by economists but not by doctors and nutritionists! Economy,
      agriculture, food processing and marketing policy changes are crucial in
      determining patterns of food consumption because the costs of foods and their
      availability, rather than policies centred on individual responsibility for
      consumer choice, are the keys to making coherent public health advances.

PMID- 16881903
TI  - Better European food labelling laws to help people with food intolerances.

PMID- 16881902
TI  - Evidence and implications for research and action--a summary.

PMID- 16881904
TI  - Protection, promotion and support of breastfeeding is now a major public health
      priority.

PMID- 16881905
TI  - Low-income mothers, nutrition and health: a systematic review of qualitative
      evidence.
AB  - Diet is a key issue for UK health policies, particularly in relation to poorer
      socio-economic groups. From a public health perspective, the government's role is
      to help low-income families to make healthy food choices, and to create the
      conditions to enable them to make healthy decisions. Arguably, however, current
      policy on nutrition and health is influenced by individualist and behavioural
      perspectives, which fail to take into account the full impact of structural
      factors on food choices. This paper draws on a systematic review of qualitative
      studies that prioritize low-income mothers' accounts of 'managing' in poverty,
      synthesizing a subset of studies that focus on diet, nutrition and health in poor
      families. Synthesis findings are explored in the context of dominant discourses
      concerning individual responsibility for health and gendered societal values
      concerning 'good' mothering. The paper concludes that a shift in emphasis in
      health policies, affording a higher priority to enabling measures that tackle the
      underlying determinants of health, would be advantageous in reducing nutritional
      inequities for low-income mothers and their children.

PMID- 16881906
TI  - An evaluation of the breastfeeding support skills of midwives and voluntary
      breastfeeding supporters using the Breastfeeding Support Skills Tool (BeSST).
AB  - The promotion of breastfeeding has been established as a global public health
      issue. Despite this global agenda, breastfeeding initiation and duration rates
      remain low in many countries. The lack of provision of adequate support to the
      breastfeeding mother is an important contributory factor to shorter duration of
      breastfeeding. Health professionals and voluntary breastfeeding supporters are in
      a prime position to work collaboratively to provide comprehensive support to the
      breastfeeding mother. However, a comparative evaluation of the breastfeeding
      support skills of voluntary breastfeeding supporters and health professionals has
      never been conducted. This study aimed to assess the breastfeeding support skills
      of midwives and Breastfeeding Network (BfN) supporters. Breastfeeding support
      skills were assessed using a between-subjects design conducted with 15 midwives
      and 15 BfN supporters in the north-west of England. Support skills were measured
      using the prevalidated Breastfeeding Support Skills Tool (BeSST), a questionnaire
      and video tool. Total scores on the BeSST were significantly higher in the BfN
      group (mean = 42.5 +/- 6.4 SD) than in the midwife group (mean = 30.7 +/- 8.2 SD)
      [t (26.5) = 4.4, P < 0.0001]. The BfN group has the breastfeeding support skills
      necessary to provide adequate assistance for breastfeeding mothers. An
      interagency and interdisciplinary collaborative model is crucial to developing a
      coherent and cohesive approach to the support infrastructure for breastfeeding
      women.

PMID- 16881907
TI  - Views of breastfeeding difficulties among drop-in-clinic attendees.
AB  - Breast-milk is the optimum form of nutrition for the first 6 months of life.
      However, breastfeeding rates in the UK are low and static compared to other
      European countries and those in the North-west of England in the UK are even
      lower. Of the women who initiate breastfeeding, many cease in the first month
      following the birth for reasons that might be avoided. To try and prevent this,
      UNICEF Baby Friendly Hospital Initiative (BFHI) 'Ten Steps to Successful
      Breastfeeding' state that maternity facilities should foster the development of
      support groups for breastfeeding women. The aim of the present study was to
      describe breastfeeding difficulties reported by women who attended the infant
      feeding clinic at a Women's Hospital in the North-west of England. During the
      study period, the clinic was attended mainly by primiparous mothers who were
      educated beyond 18 years of age and of higher socio-economic status. They
      presented with a variety of problems including baby not latching on, concerns
      about baby's weight gain/loss, sore nipples and advice about expressing milk in
      preparation for return to work. The women highlighted the importance of meeting
      other mothers and having someone to talk to who understood what they were going
      through. Inconsistent information/lack of detailed knowledge from health
      professionals was cited as contributing to breastfeeding difficulties. A number
      of women reported that expert hands-on, one-to-one support, was invaluable and
      many felt they were able to continue breastfeeding but without the support, they
      may have given up.

PMID- 16881908
TI  - Household dietary strategies to enhance the content and bioavailability of iron,
      zinc and calcium of selected rice- and maize-based Philippine complementary
      foods.
AB  - Philippine complementary foods are predominantly plant-based, with a low content
      of readily available iron, zinc, and calcium, and a relatively high amount of
      phytate, a potent inhibitor of mineral absorption. Some of the phytate is water
      soluble, and hence can be removed by soaking. In this study we have compared the
      iron, zinc, and calcium content, and estimated iron and zinc bioavailability of
      rice- and maize-based Filipino complementary foods prepared with and without
      soaking and/or enrichment with chicken liver, egg yolk, small soft-boned fish,
      and mung bean grits. Analysis of iron, zinc, and calcium were performed by atomic
      absorption spectrometry, and phytate (based on hexa-(IP6) and penta-inositol
      phosphate (IP5) by HPLC; corresponding [Phy]/[Fe] and [Phy]/[Zn] molar ratios
      were calculated as predictors of iron and zinc bioavailability. Addition of
      chicken liver, followed by egg yolk, resulted in the greatest increases in iron
      and zinc content for both the rice- and maize-based complementary foods, whereas
      addition of small dried fish with bones had the greatest effect on calcium. The
      IP5 + IP6 content and [Phy]/[Zn] molar ratios were higher in the maize- than rice
      based complementary foods, and were reduced by soaking, although only the maize
      plus mung bean grits, with and without soaking, had [Phy]/[Zn] molar ratios above
      15. Enrichment with animal protein or soaking has the potential to enhance the
      content of absorbable iron, zinc, and probably calcium to varying degrees in rice
      and maize-based Philippine complementary foods.

PMID- 16881910
TI  - Weight monitoring of breastfed babies in the United Kingdom--interpreting,
      explaining and intervening.
AB  - Weighing infants in their first 6 months is an important aspect of growth
      monitoring and a common activity of child health care services worldwide. During
      the same 6 months, support for establishing breastfeeding and the promotion of
      continued exclusive breastfeeding are important activities of health
      professionals. Parents and health professionals may perceive conflicts between
      achieving both robust growth and continuing breastfeeding. In this narrative
      review, the literature on weighing breastfed babies in the United Kingdom is
      examined. A companion paper examined issues of growth charts, scales and weighing
      frequency and accuracy. This paper considers issues of interpretation of the
      plotted weight values for individual breastfed babies, noting the complexities of
      growth patterns, which may lead to difficulties of accurate identification of
      those individuals whose growth merits further investigation. Little attention has
      been given to issues of explaining the interpreted growth curves to parents and
      this issue is explored and noted as of importance for further study. Research
      evidence on choosing appropriate interventions to improve the growth of breastfed
      babies is reviewed. The paucity of such evidence leads to suggestions for future
      study. This review gathers together a wide range of literature from many
      different perspectives, with the hope of informing weight monitoring practice so
      that this can both identify infants whose weight may be of concern, and who may
      need appropriate intervention, and support continued breastfeeding.

PMID- 16881911
TI  - Risk of stillbirth in relation to maternal haemoglobin concentration during
      pregnancy.
AB  - The authors determined the association between maternal haemoglobin concentration
      measured at <28 weeks' gestation and late fetal death at >or=28 weeks' gestation
      (stillbirth). Data were derived from the National Maternal and Infant Health
      Survey--a nationally representative survey of US deliveries in 1988. Analysis was
      restricted to women with a singleton live birth (n = 4,199) or a stillbirth (n =
      1,375) for whom maternal prenatal care, haemoglobin, smoking status and
      gestational age data were available. Haemoglobin concentrations during first and
      second trimesters, respectively, were classified as mild (10.0 to <11.0 and 9.5
      to <10.5 g dL(-1)) or moderate (9.0 to <10.0 and 8.5 to <9.5 g dL(-1)) anaemia,
      or high haemoglobin (>or=14.6 g dL(-1) in either trimester). Hazard ratios (HR)
      and 95% confidence intervals (CI) for stillbirth were derived from discrete
      proportional hazards regression models after adjusting for confounders.
      Stillbirth was not associated with mild anaemia or high haemoglobin in either the
      first or second trimester of pregnancy. Moderate anaemia measured before 28
      weeks' gestation was significantly associated with an increased risk of
      stillbirth among non-black women (adjusted HR: 4.4; 95% CI: 1.02, 19.01).
      Moderate anaemia was not associated with stillbirths among black women. Further
      investigation regarding causal mechanisms for this association is warranted.

PMID- 16881913
TI  - Mother's reactions to a skills-based breastfeeding promotion intervention.
AB  - We interviewed women who participated in a breast-feeding promotion intervention
      study about whether and how participation affected their infant feeding choices,
      and if they would recommend such an intervention to others. The larger study, a
      randomized controlled trial (RCT) of an individualized, pre- and post-natal
      lactation consultant (LC) intervention, enrolled 382 low-income primarily Black
      and Hispanic women in New York City. Twenty-one women completed qualitative exit
      interviews for this study (11 from the Intervention group and 10 Controls).
      Several of the Controls stated that the post-partum study interviews were a
      source of support, and made them more conscious of how they fed their infant. The
      Intervention Group was asked about contacts with the study 'Mother-Baby
      specialist' (i.e. LC), including what was and wasn't helpful. The Intervention
      Group participants described the Mother-Baby Specialist as key in their decision
      to initiate and maintain breastfeeding. They credit her direct skills and
      positive reinforcement with their confidence and perseverance to breastfeed. The
      success of the intervention is attributed to technical assistance from a trained
      lactation consultant within the context of a relationship built on encouragement,
      guidance and support.

PMID- 16881912
TI  - The composition of polyunsaturated fatty acids in erythrocytes of lactating
      mothers and their infants.
AB  - Long-chain polyunsaturated fatty acids (LCPUFA) in breastmilk, specifically
      docosahexaenoic acid (DHA), are important for infant brain development. Accretion
      of DHA in the infant brain is dependent on DHA-status, intake and metabolism. The
      aim of this study was to describe changes in maternal and infant erythrocyte
      (RBC) DHA-status during the first four months of lactation. We examined 17
      mothers and their term infants at 1, 2 and 4 months of age. Milk samples and RBC
      from the mothers and infants were obtained and analysed for fatty acid
      composition. Comparative analysis of the results showed that the content of DHA
      in maternal RBC-phosphatidylcholine (PE) decreased over the four month period and
      this was not accompanied by a decrease in DHA in infant RBC-PE (P = 0.005). The
      ratio of n-6 PUFA to n-3 PUFA increased over time in maternal RBC-PE, but not in
      infant RBC-PE (P < 0.001). The level of 22:5n-6 and the ratio of LCPUFA to
      precursor PUFAs in infant RBC was higher than in maternal RBC phospholipids. (P =
      and P < 0.001 respectively). We found a decrease in the level of LCPUFA in milk,
      specifically AA. However, we did not observe a significant decrease in milk DHA,
      which may have been due to two outliers. These results indicate better DHA-status
      and a higher n-3/n-6 PUFA in RBC of infants than in mothers. Whether these
      differences reflect preferential n-3 PUFA transfer via breastmilk or differences
      in PUFA-metabolism and utilization remains to be shown.

PMID- 16881914
TI  - Wheezing and eczema in relation to infant anthropometry: evidence of
      developmental programming of disease in childhood.
AB  - Early life factors and, in particular, the fetal environment have been suggested
      to programme risk of allergic disease in later life. Diversion of nutrients away
      from immune organs towards the brain, a process termed brain sparing, has been
      proposed as a mechanism underpinning this association. The study population was a
      group of 256 seven-year old children from the UK recruited from two general
      practitioner surgeries. Historical anthropometric data from birth to age three
      and current anthropometry were assessed as predictors of parent-reported wheeze
      and eczema. Eczema at seven years was not related to any anthropometric indices
      at birth or during infancy. A smaller head circumference at 10-15 days of age was
      noted in children with current wheeze at age 7 years (P = 0.018) and this
      relationship persisted after adjustment for current anthropometry and
      confounders. Comparison of children with head circumference over 36.5 cm at 10-15
      days with those with head circumference under 35.5 cm, showed reduced odds for
      wheeze at 7 years (OR 0.12, 95% CI 0.03-0.44, P(trend) = 0.009). These data
      suggest that factors that determine fetal growth may be associated with wheeze in
      childhood and support the developmental origins of health and disease hypothesis.
      Brain sparing does not appear to play a role in this early life programming.

PMID- 16881916
TI  - Evidence based nutrition and health claims on foods: a renaissance?

PMID- 16881917
TI  - A critical analysis of UK public health policies in relation to diet and
      nutrition in low-income households.
AB  - Diet and nutrition, particularly among low-income groups, is a key public health
      concern in the UK. Low levels of fruit and vegetable consumption, and obesity,
      especially among children, have potentially severe consequences for the future
      health of the nation. From a public health perspective, the UK government's role
      is to help poorer families make informed choices within healthy frameworks for
      living. However, the question is - to what extent are such policies in accordance
      with lay experiences of managing diet and nutrition on a low-income? This paper
      critically examines contemporary public health policies aimed at improving diet
      and nutrition, identifying the underlying theories about the influences on
      healthy eating in poor families, and exploring the extent to which these
      assumptions are based on experiential accounts. It draws on two qualitative
      systematic reviews - one prioritizing low-income mothers' accounts of 'managing'
      in poverty; and the other focusing on children's perspectives. The paper finds
      some common ground between policies and lay experiences, but also key
      divergencies. Arguably, the emphasis of public health policy on individual
      behaviour, coupled with an ethos of empowered consumerism, underplays material
      limitations on 'healthy eating' for low-income mothers and children. Health
      policies fail to take into account the full impact of structural influences on
      food choices, or recognize the social and emotional factors that influence diet
      and nutrition. In conclusion, it is argued that while health promotion campaigns
      to improve low-income families' diets do have advantages, these are insufficient
      to outweigh the negative effects of poverty on nutrition.

PMID- 16881918
TI  - Relationships of psychosocial factors to dietary intakes of preadolescent girls
      from diverse backgrounds.
AB  - Family and personal factors that might be related to the development of food
      selection and eating patterns have not been well studied in children. The aim of
      this study was to examine whether such psychosocial factors differ in girls from
      four culturally diverse Girl Scout troops and how these factors are associated
      with dietary intakes. The social measures and dietary assessments were all
      obtained at baseline on subjects who were participating in a small nutrition
      education programme. The programme enrolled girls and one parent for each girl
      from four Girl Scout troops in Detroit, Michigan. The social factors assessed
      included girls' emotionality and use of food to regulate emotions, their general
      attitudes about health, eating and body image, and self-perceptions of their
      competence. Dietary intakes also were assessed in both the girls and their
      parents. There were large differences between troops in ethnicity and parent
      education level, and there were differences in dietary intakes as well. The
      psychosocial factors assessed in this study, however, did not differ
      significantly by troop. When the psychosocial factors were examined for their
      relationships to dietary factors, there was an indication that families which
      reported higher self-competence and academic competence in their daughters also
      had healthier eating patterns in their daughters. This was a small study, but the
      data suggest that simple comparisons between ethnic groups may not adequately
      capture the complexity of family and psychosocial factors contributing to good
      dietary practices.

PMID- 16881919
TI  - The development and delivery of a practice-based breastfeeding education package
      for general practitioners in the UK.
AB  - Growing acceptance that measurable improvements in public health, particularly in
      lower-income groups, could be achieved by increasing the incidence of
      breastfeeding has focused attention on the current lack of educational provision
      in breastfeeding issues for many health professionals. An audit of general
      practitioners in one area of northern England revealed an interest in receiving
      breastfeeding training. Department of Health funding was obtained by the
      breastfeeding subgroup of the local Maternity Services Liaison Committee to
      develop, deliver and evaluate a practice-based educational session supplemented
      by a resource pack. Over a 12-month period, 22 practices received the session and
      the project was evaluated using an illuminative evaluation model. Response rates
      to two evaluation questionnaires of 81% (133/164) and 62.5% (65/104) were
      achieved and findings indicated high levels of satisfaction with the session and
      its accompanying resource pack. Qualitative data related to perceived influence
      on future practice were subjected to thematic network analysis and revealed four
      main (organizing) themes: the acquisition of greater knowledge, improved access
      to resources, a proactive approach to breastfeeding support and the creation of a
      breastfeeding-friendly environment. The illuminative evaluation also identified
      recurring issues that could impact on any attempt to replicate or adapt this
      project; these were the influence of personal breastfeeding experiences, the
      desire for greater interaction during the training session and the wider
      implications for practice education of multidisciplinary attendance.

PMID- 16881920
TI  - Turning policy into practice: more difficult than it seems. The case of
      breastfeeding education.
AB  - Breastfeeding is increasingly recognized as a health policy priority. To achieve
      real change in breastfeeding rates, those who advise and support childbearing
      women need to be appropriately educated and trained so that they do not disrupt
      breastfeeding. The aim of this study was to conduct a needs analysis about
      breastfeeding training among a range of people who advise and support
      breastfeeding women, including breastfeeding women themselves, to contribute to
      future provision of education. A qualitative, interview-based study was conducted
      in one northern UK city with practitioners who support breastfeeding, and
      breastfeeding women, selected using purposive sampling. Individual (n = 73) and
      group (n = 9) interviews were conducted. Detailed notes were returned to each
      respondent for checking. Information was organized into themes. Coding was
      charted to enable comparison by theme and case. Four main themes emerged:
      perspectives of breastfeeding women; feeling (un)prepared to support
      breastfeeding; fragmentation of knowledge; and provision of education about
      breastfeeding. A deficit in education and training for all professional groups
      was identified. There was little evidence of informal shared learning among
      professional groups, and no evidence of usual mechanisms to ensure education and
      practice standards. Doctors received very little formal education; most relied on
      other health professionals to provide this expertise. Students encountered a
      chaotic learning environment where it was not possible to observe sound,
      consistent practice. Voluntary breastfeeding supporters felt well-prepared. The
      results call into question the potential for health services to respond to policy
      recommendations that support increased rates of breastfeeding.

PMID- 16881921
TI  - The quality of the diet in Malawian children with kwashiorkor and marasmus.
AB  - Nutritionists have suggested that kwashiorkor is related to low dietary protein
      and/or antioxidant intake. This study explored the hypothesis that among Malawian
      children with severe malnutrition, those with kwashiorkor consume a diet with
      less micronutrient- and antioxidant-rich foods, such as fish, eggs, tomatoes and
      orange fruits (mango, pumpkin and papaya), than those with marasmus. A case
      control method with a food frequency questionnaire was used to assess the
      habitual diet. Children with severe childhood malnutrition presenting to the
      central hospital in Blantyre, Malawi during a 3-month period in 2001 were
      eligible to participate. The food frequency questionnaire collected data about
      foods consumed by siblings <60 months of age in the home. It was assumed that the
      habitual diet of all siblings 1-5 years old in the same home was similar. Dietary
      diversity was assessed using a validated method, with scores that ranged from 0
      to 7. Regression modelling was used to control for demographic and disease
      covariates. A total of 145 children with kwashiorkor and 46 with marasmus were
      enrolled. Children with kwashiorkor consumed less egg and tomato than those with
      marasmus: 17 (15) vs. 24 (31) servings per month for egg, mean (SD), P < 0.01 and
      27 (17) vs. 32 (19) servings per month for tomato, P < 0.05. Children with
      kwashiorkor had a similar dietary diversity score as those with marasmus, 5.06
      (0.99) vs. 5.02 (1.10), mean (SD). Further research is needed to determine what
      role consumption of egg and tomato may play in the development of kwashiorkor.

PMID- 16881925
TI  - Diet, physical inactivity and the prevalence of constipation throughout and after
      pregnancy.
AB  - Few studies appear to have investigated the prevalence of constipation for all
      three trimesters of the gestative period, or indeed after birth. Using a
      prospective 4- to 7-day weighed food diary, International Physical Activity
      Questionnaire and 7-day bowel habit diary, dietary factors, physical activity
      levels and bowel habit parameters were assessed and examined concurrently at
      weeks 13, 25, 35 of pregnancy and 6 weeks post-partum. Ninety-four primiparous
      pregnant women were initially recruited, and 72, 59, 62 and 55 completed the
      first, second, third trimester and post-partum study stages, respectively. Key
      dietary factors and physical activity levels were compared between the
      constipated and non-constipated groups from each of the three trimesters and
      after parturition. Compared with non-constipated mothers-to-be, constipated
      participants consumed statistically significantly less water in the first
      trimester (P = 0.04), more food in the second trimester (P = 0.04), and less iron
      (P = 0.02) and food (P = 0.04) in the third trimester and after birth,
      respectively. No statistically significant differences were identified between
      light, moderate and vigorous physical activity levels when groups were compared.
      This study demonstrates that dietary factors may play a role in terms of
      preventing, or alleviating, bowel habit perturbations both throughout and after
      pregnancy. Further research is required to investigate the interrelationship
      between physical activity and constipation during and after pregnancy.

PMID- 16881926
TI  - Acceptability, feasibility and affordability of infant feeding options for HIV
      infected women: a qualitative study in south-west Nigeria.
AB  - The objective of this study was to explore the acceptability, feasibility,
      affordability, safety and sustainability of replacement feeding options for HIV
      infected mothers in Ile-Ife, in south-west Nigeria. Six focus group discussions
      were conducted with a purposive sample of mothers, fathers and grandmothers. The
      HIV status of all participants was unknown to investigators. All text data were
      analysed using the Text-based Beta Software program. With regard to the
      acceptability of replacement feeds, respondents perceived the stigma associated
      with not breastfeeding to be an important consideration. In this community,
      breastfeeding is the norm--even though it is not necessarily exclusive. For
      infected mothers who choose to breastfeed exclusively and then to wean their
      infants before 6 months of age, respondents did not anticipate early cessation of
      breastfeeding to be problematic. Respondents noted that acceptable replacement
      foods included infant formula, soy milk and cow's milk. Barriers to replacement
      feeding that were mentioned included: the high costs of replacement foods and
      fuel for cooking; an unreliable supply of electrical power; poor access to safe
      water; and poor access to storage facilities. The research confirms the
      difficulty of replacement feeding for HIV-infected mothers in sub-Saharan Africa.
      The results also provide the basis for new issues and hypothesis for future
      research in other communities with similar socio-cultural and economic
      characteristics.

PMID- 16881927
TI  - Breastfeeding and family life.
AB  - The problems faced by breastfeeding mothers are well documented. However, the
      influence of social networks has mainly received attention solely through the
      eyes of the women. Therefore, we explored the views of the family as a whole.
      This exploratory study utilizes semi-structured interviews, diaries and
      questionnaires. A purposive sample of 24 women and their families, from a
      hospital in the north-west of England were invited to participate. Questionnaire
      data were analysed descriptively. Diaries and interviews were analysed using an
      open coding mechanism to identify emergent themes. Twenty-three women and 27 of
      their family members participated. Questionnaire data showed that the majority of
      women (n = 17) expected to breastfeed for more than 3 months; 12 actually did
      this. Women anticipated that family members would provide the main source of
      breastfeeding support. Three main themes emerged from the interviews and diaries:
      "moving with the times", "marketable commodity" and "disparate communications".
      The authors conclude that multi-layered approach to breastfeeding promotion and
      support should be considered. Society needs to proactively encourage a positive
      breastfeeding culture, family members need direction on how to support a woman to
      breastfeed and women need to be able to articulate their individual requirements.
      Midwives could be instrumental in supporting such needs and facilitating change.

PMID- 16881928
TI  - Exploring women's views of breastfeeding: a focus group study within an area with
      high levels of socio-economic deprivation.
AB  - There is ample evidence of the short- and long-term health benefits of
      breastfeeding for mothers and infants, yet breastfeeding rates remain low in the
      UK, particularly in areas of high social deprivation. It is imperative that
      appropriate strategies are utilized to support more women to initiate and
      continue breastfeeding. This study used focus group methodology to explore
      women's views in relation to breastfeeding. The study was conducted within an
      area with high levels of socio-economic deprivation in the north-east of England
      and aimed to identify local barriers to breastfeeding, influences on choice of
      infant-feeding method and strategies which might improve breastfeeding rates.
      Focus group discussions were conducted with low-income women, adolescent women
      and women from a minority ethnic group. The five key themes that emerged from the
      data were: society's negative attitudes towards breastfeeding; the influence of
      family and friends and the experience on choice of method of infant feeding; lack
      of knowledge of some aspects of infant feeding; perceptions of professional
      support; and women's positive and negative experiences of breastfeeding.
      Recommendations for promoting and supporting breastfeeding include improving
      facilities to breastfeed in public, enhancing the provision of information,
      addressing conflicting advice and poor professional practice and implementing
      support mechanisms. The findings and recommendations have been used to develop a
      breastfeeding strategy to meet local needs. This project was funded by the
      English Department of Health Infant Feeding Initiative.

PMID- 16881929
TI  - Multi-micronutrient Sprinkles including a low dose of iron provided as
      microencapsulated ferrous fumarate improves haematologic indices in anaemic
      children: a randomized clinical trial.
AB  - Home-fortification of complementary foods with micronutrients (including iron) as
      Sprinkles is a new strategy to control iron deficiency and anaemia in developing
      countries. However, the most effective dose and form of iron is not known. The
      purpose of this study was to compare the efficacy of various doses (12.5, 20 or
      30 mg) and treatment methods (multi-micronutrient Sprinkles vs. ferrous sulphate
      drops) on haemoglobin (Hb) concentration after 8 weeks of treatment in anaemic
      children. In total, 133 anaemic Ghanaian children (Hb 70-99 g L(-1)) aged 6-18
      months were randomly assigned to one of five daily interventions for 8 weeks. Out
      of the five interventions, four used Sprinkles, and one used iron drops. Of the
      four Sprinkles groups, three included 12.5, 20 or 30 mg of iron as ferrous
      fumarate, and one included 20 mg of iron as ferric pyrophosphate. The iron drops
      group included 12.5 mg of iron as liquid ferrous sulphate. Hb concentrations were
      measured at baseline, week 3 and week 8. The primary outcome measure was Hb
      concentration at 8 weeks after treatment. We compared differences in Hb and
      ferritin concentrations and prevalence of iron deficiency anaemia (Hb < 100 g L(
      1) and soluble transferrin receptor concentrations >8.5 mg L(-1)) from baseline
      to 8 weeks within and between groups. Adherence and reporting of side effects
      (staining of the teeth, ease of use, diarrhoea and darkening of stools) were
      compared between groups. Mean change in Hb was 1.4 g L(-1) (SD = 1.8) (P =
      0.0001). Change in Hb concentrations from baseline to 8 weeks was significant in
      all groups (P = 0.0001-0.0007), with no differences across groups. Geometric
      means of serum ferritin varied from 18.6 to 44.0 microg L(-1) at baseline. At
      week 8, these means were in the interval of 48.0-78.3 microg L(-1), with no group
      differences. Prevalence of iron deficiency anaemia decreased significantly from
      baseline to 8 weeks in all groups with the exception of the iron drops group,
      with no group differences. Adherence was lower in the drops group (64%) as
      compared with Sprinkles groups (84%). Greater staining of the teeth and less ease
      of use were reported in the drops group as compared with Sprinkles groups. A dose
      as low as 12.5 mg of iron as ferrous fumarate when provided as Sprinkles may be
      effective in anaemic children.

PMID- 16881930
TI  - Relative validity of a dietary interview for assessing infant diet and compliance
      in a dietary intervention trial.
AB  - The objective of this study was to assess the relative validity of a dietary
      interview method for use in an infant population. A dietary interview covering a
      1-month period was completed during a study visit at 3 or 6 months of age. It
      included structured questions and a short food frequency questionnaire (FFQ). The
      information was compared with data from two 48-h recall interviews conducted
      during the month previous to the study visit. The agreement between the FFQ and
      48-h recalls was analysed as proportion of subjects classified into the same
      categories of consumption frequency and by the kappa analysis. A total of 100
      subjects, at the age of 2-3 months (n = 50) and 5-6 months (n = 50), were
      included. The kappa values for breastmilk and study formula ranged from 0.82 to
      0.95, indicating very good agreement. The agreement for other foods and vitamin D
      supplementation ranged from fair to very good. We also found a strong correlation
      for the reported amount of study formula consumed per feeding at 3 months (r(s) =
      0.87, n = 24) and 6 months of age (r(s) = 0.73, n = 35) between the questionnaire
      and 48-h recall data. However, the average amount of study formula per feeding
      was significantly higher when estimated for a 1-month period, compared with a
      mean calculated from the two 48-h recalls. As a conclusion, the interview was
      found to be a useful tool for assessing diet and compliance in a dietary
      intervention for infants.

PMID- 16881933
TI  - Incidence and risk of venous thromboembolism in patients with verified arterial
      thrombosis: a population study based on 23,796 consecutive autopsies.
AB  - BACKGROUND: The relationship between atherothrombotic disease and venous
      thromboembolism (VTE) remains unclear. PATIENTS AND METHODS: In a cohort of
      23,796 consecutive autopsies, performed using a standardized procedure and
      representing 84% of all in-hospital deaths between 1970 and 1982 in an urban
      Swedish population, we investigated the relationship between verified arterial
      thrombosis and VTE, with the hypothesis that patients with thrombosis in major
      artery segments have increased odds of VTE. RESULTS: We found an increased risk
      of VTE in patients with arterial thrombosis (Odds ratio; OR adjusted for gender
      and age 1.4, 95% confidence interval; CI 1.3-1.5) (P < 0.001). Patients with
      cervico-cranial and peripheral artery thrombosis had an excess risk even when
      controlling for age and major concomitant diseases. A negative association
      between coronary thrombosis and VTE in the univariate analysis (OR 0.7; 95% CI
      0.6-0.8) (P < 0.001), was less pronounced in the multivariate analysis (OR 0.8;
      95% CI 0.7-1.0) (P = 0.016). CONCLUSIONS: A positive association between
      atherothrombosis and VTE was confirmed, except in patients with coronary
      thrombosis, where IHD as competing death cause is a possible confounder. Our
      findings indicate a potential for directed prevention, but may also imply
      similarities in etiology.

PMID- 16881934
TI  - Prolonged prophylaxis with dalteparin to prevent late thromboembolic
      complications in patients undergoing major abdominal surgery: a multicenter
      randomized open-label study.
AB  - BACKGROUND: Patients undergoing major abdominal surgery carry a high risk of
      venous thromboembolism (VTE), but the optimal duration of postoperative
      thromboprophylaxis is unknown. OBJECTIVES: To evaluate the efficacy and safety of
      thromboprophylaxis with the low molecular weight heparin (dalteparin),
      administered for 28 days after major abdominal surgery compared to 7 days'
      treatment. PATIENTS/METHODS: A multicenter, prospective, assessor-blinded, open
      label, randomized trial was performed in order to evaluate prolonged
      thromboprophylaxis after major abdominal surgery. In total, 590 patients were
      recruited, of whom 427 were randomized and received at least 1 day of study
      medication, and 343 reached an evaluable endpoint. The primary efficacy endpoint
      was objectively verified VTE occurring between 7 and 28 days after surgery. All
      patients underwent bilateral venography at day 28. RESULTS: The cumulative
      incidence of VTE was reduced from 16.3% with short-term thromboprophylaxis
      (29/178 patients) to 7.3% after prolonged thromboprophylaxis (12/165) (relative
      risk reduction 55%; 95% confidence interval 15-76; P=0.012). The number that
      needed to be treated to prevent one case of VTE was 12 (95% confidence interval 7
      44). Bleeding events were not increased with prolonged compared with short-term
      thromboprophylaxis. CONCLUSIONS: Four-week administration of dalteparin, 5000 IU
      once daily, after major abdominal surgery significantly reduces the rate of VTE,
      without increasing the risk of bleeding, compared with 1 week of
      thromboprophylaxis.

PMID- 16881935
TI  - Fibrinogen plasma levels modify the association between the factor XIII Val34Leu
      variant and risk of coronary artery disease: the EPIC-Norfolk prospective
      population study.
AB  - BACKGROUND: The factor (F) XIII Val34Leu variant has been implicated in coronary
      artery disease (CAD). In vitro evidence suggests an interaction between this
      variant and fibrinogen concentrations in determining thrombus structure.
      OBJECTIVES: To test whether this interaction is relevant in influencing coronary
      risk in apparently healthy individuals. METHODS: In an 8-year prospective
      population study of 25 663 men and women, we compared 898 apparently healthy men
      and women developing incident CAD with 1580 matched controls. RESULTS: Overall,
      the FXIII Val34Leu variant was not associated with the risk of future CAD.
      However, a significant interaction existed between the Val34Leu variant and
      fibrinogen levels for the risk of future CAD (P = 0.004). Among people in the
      lowest tertile of fibrinogen concentrations, LeuLeu carriers had an odds ratio
      (OR) of 2.88 (95% confidence interval; CI 1.24-6.74) compared to wild-type
      individuals (P for linearity = 0.003). By contrast, among those in the highest
      fibrinogen tertile, LeuLeu carriers were had a lower risk than wild-type
      individuals (OR 0.47, 95% CI 0.18-1.17, P for linearity = 0.1). CONCLUSIONS: Our
      results suggest that a significant gene-covariate interaction exists between the
      FXIII Val34Leu variant and fibrinogen levels. Relationships between genotype and
      disease risk may be altered by biological covariates. Simplistic paradigms of
      gene or biomarker associations are unlikely to fully characterize disease risk in
      populations.

PMID- 16881939
TI  - Impact of health literacy on longitudinal asthma outcomes.
AB  - BACKGROUND: The impact of health literacy on longitudinal asthma outcomes is not
      known. OBJECTIVES: To measure the association between health literacy and asthma
      outcomes and to assess how health literacy affects outcomes through covariates.
      DESIGN: Longitudinal cohort. PATIENTS: One hundred and seventy-five adult asthma
      patients. MEASUREMENTS: Independent variables measured at enrollment included
      demographic and asthma characteristics, depressive symptoms, self-efficacy, and
      asthma knowledge. Health literacy was measured with the Test of Functional Health
      Literacy in Adults. Outcomes were Asthma Quality of Life Questionnaire and SF-36
      scores and emergency department utilization for asthma measured every 3 to 6
      months for 2 years. The effects of health literacy on outcomes and interactions
      between health literacy and covariates were measured with multivariable models.
      RESULTS: The mean age of study participants was 42 years, and 83% were women.
      Less health literacy was associated with worse quality of life, worse physical
      function, and more emergency department utilization for asthma over 2 years (P<
      or = .05 for all comparisons). In multivariable analysis, health literacy did not
      remain statistically significant with any of the outcomes. Although the magnitude
      of its effect on emergency department utilization remained relatively intact, its
      effects on quality of life and functional status became attenuated with the
      sequential addition of covariates, particularly asthma knowledge. CONCLUSIONS:
      Less health literacy was associated with poor longitudinal asthma outcomes. This
      relationship was both direct and indirect through effects on other independent
      variables, particularly patients' knowledge of asthma and self-management.
      Efforts to improve asthma outcomes should focus on improving literacy skills that
      are required to learn, understand, and implement effective self-management.

PMID- 16881938
TI  - Limited literacy and mortality in the elderly: the health, aging, and body
      composition study.
AB  - BACKGROUND: While limited literacy is common and its prevalence increases with
      age, no prospective study has assessed whether limited literacy is associated
      with mortality in older adults. OBJECTIVE: To assess the association of limited
      literacy with mortality. DESIGN AND SETTING: Five-year prospective study from
      1999 to 2004 of community-dwelling elders from Memphis, TN, and Pittsburgh, PA,
      who were from the Health, Aging, and Body Composition study. Subjects' literacy
      was assessed with the Rapid Estimate of Adult Literacy in Medicine. Scores were
      categorized into limited (0 to 8th grade reading level) or adequate literacy (>
      or = 9th grade reading level). PARTICIPANTS: Two thousand five hundred and twelve
      black and white elders without baseline functional difficulties or dementia.
      MEASUREMENTS: Time to death. RESULTS: Participants' mean age was 75.6 years, 48%
      were male, 38% were black, and 24% had limited literacy; the median follow-up
      time was 4.2 years. Compared with those with adequate literacy, those with
      limited literacy had a higher risk of death (19.7% vs 10.6%) with a hazard ratio
      (HR) of 2.03 (95% confidence intervals [CI], 1.62 to 2.55). After adjusting for
      demographics and socioeconomic status, co-morbid conditions, self-rated health
      status, health-related behaviors, health care access measures, and psychosocial
      status, limited literacy remained independently associated with mortality (HR
      1.75; 95% CI, 1.27 to 2.41). CONCLUSIONS: Limited literacy is independently
      associated with a nearly 2-fold increase in mortality in the elderly. Given the
      growth of the aging population and the prevalence of chronic diseases, the
      mechanisms by which limited literacy is associated with mortality in the elderly
      warrant further investigation.

PMID- 16881940
TI  - Impact of health literacy on depressive symptoms and mental health-related:
      quality of life among adults with addiction.
AB  - BACKGROUND: Health literacy has been linked to health status in a variety of
      chronic diseases. However, evidence for a relationship between health literacy
      and mental health outcomes is sparse. OBJECTIVE: We hypothesized that low
      literacy would be associated with higher addiction severity, higher levels of
      depressive symptoms, and worse mental health functioning compared with those with
      higher literacy in adults with alcohol and drug dependence. METHODS: The
      association of literacy with multiple mental health outcomes was assessed using
      multivariable analyses. Measurement instruments included the Rapid Estimate of
      Adult Literacy in Medicine (REALM), the Center for Epidemiologic Studies
      Depression (CES-D) scale, the Mental Component Summary scale of the Short Form
      Health Survey, and the Addiction Severity Index for drug and alcohol addiction.
      Subjects included 380 adults recruited during detoxification treatment and
      followed prospectively at 6-month intervals for 2 years. Based on the REALM,
      subjects were classified as having either low (< or = 8th grade) or higher (> or
      = 9th grade) literacy levels. RESULTS: In longitudinal analyses, low literacy was
      associated with more depressive symptoms. The adjusted mean difference in CES-D
      scores between low and high literacy levels was 4 (P<.01). Literacy was not
      significantly associated with mental health-related quality of life or addiction
      severity. CONCLUSIONS: In people with alcohol and drug dependence, low literacy
      is associated with worse depressive symptoms. The mechanisms underlying the
      relationship between literacy and mental health outcomes should be explored to
      inform future intervention efforts.

PMID- 16881941
TI  - Literacy education as treatment for depression in patients with limited literacy
      and depression: a randomized controlled trial.
AB  - BACKGROUND: Individuals with limited literacy and those with depression share
      many characteristics, including low self-esteem, feelings of worthlessness, and
      shame. OBJECTIVE: To determine whether literacy education, provided along with
      standard depression treatment to adults with depression and limited literacy,
      would result in greater improvement in depression than would standard depression
      treatment alone. DESIGN: Randomized clinical trial with patients assigned either
      to an intervention group that received standard depression treatment plus
      literacy education, or a control group that received only standard depression
      treatment. PARTICIPANTS: Seventy adult patients of a community health center who
      tested positive for depression using the 9-question Patient Health Questionnaire
      (PHQ-9) and had limited literacy based on the Rapid Estimate of Adult Literacy in
      Medicine (REALM). MEASUREMENTS: Depression severity was assessed with PHQ-9
      scores at baseline and at 3 follow-up evaluations that took place up to 1 year
      after study enrollment. Changes in PHQ-9 scores between baseline and follow-up
      evaluations were compared between the intervention and control groups. RESULTS:
      The median PHQ-9 scores were similar in both the intervention and control groups
      at baseline (12.5 and 14, respectively). Nine-question Patient Health
      Questionnaire scores improved in both groups, but the improvement was
      significantly larger in the intervention group. The final follow-up PHQ-9 scores
      declined to 6 in the intervention group but only to 10 in the control group.
      CONCLUSIONS: There may be benefit to assessing the literacy skills of patients
      who are depressed, and recommending that patients with both depression and
      limited literacy consider enrolling in adult education classes as an adjuvant
      treatment for depression.

PMID- 16881942
TI  - Health literacy as a predictor of follow-up after an abnormal Pap smear: a
      prospective study.
AB  - BACKGROUND: Low literacy influences cervical cancer screening knowledge, and is a
      possible contributor to racial disparities in cervical cancer. OBJECTIVE: To
      examine the hypothesis that literacy predicts patient adherence to follow-up
      recommendations after an abnormal Pap smear. DESIGN: A prospective, continuity
      clinic-based study. PARTICIPANTS: From a sample of 538 women undergoing literacy
      testing at the time of Pap smear screening, we studied 68 women with abnormal Pap
      smear diagnoses. MEASUREMENTS: Literacy was assessed using the Rapid Evaluation
      of Adult Literacy in Medicine (REALM). We also measured other proxies for
      literacy, including educational attainment and physician estimates of patients'
      literacy level. Outcome measures included on-time and 1-year follow-up and
      duration of time to follow-up after an abnormal Pap smear. RESULTS: Only one
      third of the cohort adhered to follow-up recommendations. At 1 year, 25% of the
      women had not returned at all. Patients with inadequate literacy (as assessed by
      the REALM) were less likely to follow up within 1 year, although this result was
      not statistically significant (adjusted odds ratio [OR]=3.8, 95% confidence
      interval [CI]: 0.8 to 17.4). Patients subjectively assessed by their physician to
      have low literacy skills were significantly less likely to follow up within 1
      year (adjusted OR=14, 95% CI: 3 to 65). Less than high school education (hazard
      ratio (HR)= 2.3; 95% CI: 1.2, 4.6) and low physician-estimated literacy level
      (HR=3.4, 95% CI: 1.4, 8.2), but not objective literacy level, were significant
      predictors of duration of time to follow-up, adjusting for recommended days to
      follow-up and other factors. CONCLUSIONS: Among women with an abnormal Pap smear,
      those perceived by their physician to have low literacy were significantly more
      likely to fail to present for follow-up.

PMID- 16881943
TI  - Health literacy, antiretroviral adherence, and HIV-RNA suppression: a
      longitudinal perspective.
AB  - BACKGROUND: Low health literacy has been associated with worse adherence to
      antiretroviral therapy (ART) and higher HIV-RNA levels, but these relationships
      have not been evaluated in longitudinal analyses. METHODS: We evaluated literacy
      using the Rapid Estimate of Adult Literacy in Medicine (REALM) (< or = 6th grade,
      7th to 8th grade, > or = 9th grade) in the HIV-Alcohol Longitudinal Cohort study
      of HIV-infected persons with a history of alcohol problems, conducted from 1997
      to 2001. We tested HIV-RNA levels and administered a standardized questionnaire
      regarding demographics, substance use, receipt of ART, and adherence with ART,
      every 6 months for up to 7 occasions. Among the 235 subjects on ART, we
      investigated the relationship between literacy and 2 outcomes: 100% 3-day self
      reported adherence and HIV-RNA suppression (<500 copies). RESULTS: Subjects'
      literacy levels were the following: 14% < or = 6th grade, 29% 7th to 8th grade,
      and 57% > or = 9th grade. In 66% of the observations (478/725), subjects reported
      100% 3-day adherence with ART. Of the 685 HIV-RNA assays from these subjects, 62%
      had <500 copies. In unadjusted analyses, subjects with the lowest literacy level
      (< or = 6th grade) had a higher odds of adherence (odds ratio [OR] 2.23, 95%
      confidence interval 1.15 to 4.30) and HIV-RNA suppression (OR 2.01, 95%
      confidence interval 1.03 to 3.90) compared with those with > or = 9th grade
      literacy. This trend persisted but was no longer statistically significant in
      adjusted models of adherence (AOR 1.93, 95% confidence interval 0.86 to 4.31) and
      HIV-RNA suppression (AOR 1.70, 95% confidence interval 0.79 to 3.65). CONCLUSION:
      Contrary to our hypothesis, low literacy was not associated with a lower odds of
      adherence or virologic suppression in this longitudinal analysis of HIV-infected
      patients with a history of alcohol problems. Indeed, trends in these data suggest
      the possibility that low literacy may be associated with a higher odds of
      adherence and virologic suppression. These counterintuitive findings underscore
      the need to pursue a fuller understanding of the mechanisms by which literacy
      affects health outcomes.

PMID- 16881944
TI  - Health literacy and anticoagulation-related outcomes among patients taking
      warfarin.
AB  - BACKGROUND: Little is known about whether health literacy affects anticoagulation
      related outcomes. OBJECTIVE: To assess how health literacy is associated with
      warfarin knowledge, adherence, and warfarin control (measured by the
      international normalized ratio [INR]). DESIGN: Survey. PARTICIPANTS: Patients
      taking warfarin through an anticoagulation clinic. MEASUREMENTS: Health literacy
      was measured using the short-form Test of Functional Health Literacy in Adults (s
      TOFHLA), dichotomized as "limited" (score 0 to 22) and "adequate" (score 23 to
      36). We asked patients to answer questions relating to their warfarin therapy and
      used multivariable logistic regression to assess whether health literacy was
      associated with incorrect answers. We also assessed whether health literacy was
      associated with nonadherence to warfarin as well as time in therapeutic INR
      range. RESULTS: Bilingual research assistants administered the survey and s
      TOFHLA to 179 anticoagulated English- or Spanish-speaking patients. Limited
      health literacy was associated with incorrect answers to questions on warfarin's
      mechanism (adjusted odds ratio [OR] 4.8 [1.3 to 17.6]), side-effects (OR 6.4 [2.3
      to 18.0]), medication interactions (OR 2.5 [1.1 to 5.5]), and frequency of
      monitoring (OR 2.7 [1.1 to 6.7]), after adjusting for age, sex, race/ethnicity,
      education, cognitive impairment, and years on warfarin. However, limited health
      literacy was not significantly associated with missing warfarin doses in 3 months
      (OR 0.9 [0.4 to 2.0]) nor with the proportion of person-time in therapeutic INR
      range (OR 1.0 [0.7 to 1.4]). CONCLUSIONS: Limited health literacy is associated
      with deficits in warfarin-related knowledge but not with self-reported adherence
      to warfarin or INR control. Efforts should concentrate on investigating
      alternative means of educating patients on the management and potential risks of
      anticoagulation.

PMID- 16881945
TI  - Low literacy impairs comprehension of prescription drug warning labels.
AB  - BACKGROUND: Adverse events resulting from medication error are a serious concern.
      Patients' literacy and their ability to understand medication information are
      increasingly seen as a safety issue. OBJECTIVE: To examine whether adult patients
      receiving primary care services at a public hospital clinic were able to
      correctly interpret commonly used prescription medication warning labels. DESIGN:
      In-person structured interviews with literacy assessment. SETTING: Public
      hospital, primary care clinic. PARTICIPANTS: A total of 251 adult patients
      waiting for an appointment at the Louisiana State University Health Sciences
      Center in Shreveport (LSUHSC-S) Primary Care Clinic. MEASUREMENTS: Correct
      interpretation, as determined by expert panel review of patients' verbatim
      responses, for each of 8 commonly used prescription medication warning labels.
      RESULTS: Approximately one-third of patients (n=74) were reading at or below the
      6th-grade level (low literacy). Patient comprehension of warning labels was
      associated with one's literacy level. Multistep instructions proved difficult for
      patients across all literacy levels. After controlling for relevant potential
      confounding variables, patients with low literacy were 3.4 times less likely to
      interpret prescription medication warning labels correctly (95% confidence
      interval: 2.3 to 4.9). CONCLUSIONS: Patients with low literacy had difficulty
      understanding prescription medication warning labels. Patients of all literacy
      levels had better understanding of warning labels that contained single-step
      versus multiple-step instructions. Warning labels should be developed with
      consumer participation, especially with lower literate populations, to ensure
      comprehension of short, concise messages created with familiar words and
      recognizable icons.

PMID- 16881946
TI  - Predictors of medication self-management skill in a low-literacy population.
AB  - BACKGROUND: Patients' ability to manage medications is critical to chronic
      disease control. Also known as medication management capacity (MMC), it includes
      the ability to correctly identify medications and describe how they should be
      taken. OBJECTIVE: To evaluate the effects of low literacy, medication regimen
      complexity, and sociodemographic characteristics on MMC. DESIGN: Cross-sectional
      analysis of enrollment data from participants in a randomized trial.
      PARTICIPANTS: Patients with coronary heart disease in an inner-city clinic.
      MEASUREMENTS: Medication management capacity was measured with the Drug Regimen
      Unassisted Grading Scale (DRUGS), which scores subjects' ability to identify,
      open, describe the dose, and describe the timing of their medications. DRUGS
      overall and component scores were compared by literacy, Mini Mental State Exam
      score, regimen complexity (number of prescription medications), and
      sociodemographic characteristics. RESULTS: Most of the 152 participants were
      elderly (mean age 65.4 years), women (54.6%), and African American (94.1%).
      Approximately half (50.7%) had inadequate literacy skills, and 28.9% had marginal
      skills. In univariate analysis, MMC was significantly associated with literacy
      (P<.001), and this effect was driven by the ability to identify medications. In
      multivariable models, patients with inadequate literacy skills had 10 to 18 times
      the odds of being unable to identify all of their medications, compared with
      those with adequate literacy skills (P<.05). CONCLUSIONS: Adults with inadequate
      literacy skills have less ability to identify their medications. Techniques are
      needed to better educate low-literacy patients about their medications, as a
      potential strategy to enhance adherence.

PMID- 16881947
TI  - Impact of health literacy on socioeconomic and racial differences in health in an
      elderly population.
AB  - BACKGROUND: Differences in health literacy levels by race and education are
      widely hypothesized to contribute to health disparities, but there is little
      direct evidence. OBJECTIVE: To examine the extent to which low health literacy
      exacerbates differences between racial and socioeconomic groups in terms of
      health status and receipt of vaccinations. DESIGN: Retrospective cohort study.
      PARTICIPANTS (OR PATIENTS OR SUBJECTS): Three thousand two hundred and sixty
      noninstitutionalized elderly persons enrolling in a Medicare managed care plan in
      1997 in Cleveland, OH; Houston, TX; South Florida; and Tampa, FL. MEASUREMENTS:
      Dependent variables were physical health SF-12 score, mental health SF-12 score,
      self-reported health status, receipt of influenza vaccine, and receipt of
      pneumococcal vaccine. Independent variables included health literacy, educational
      attainment, race, income, age, sex, chronic health conditions, and smoking
      status. RESULTS: After adjusting for demographic and health-related variables,
      individuals without a high school education had worse physical and mental health
      and worse self-reported health status than those with a high school degree.
      Accounting for health literacy reduced these differences by 22% to 41%. Black
      individuals had worse self-reported health status and lower influenza and
      pneumococcal vaccination rates. Accounting for health literacy reduced the
      observed difference in self-reported health by 25% but did not affect differences
      in vaccination rates. CONCLUSIONS: We found that health literacy explained a
      small to moderate fraction of the differences in health status and, to a lesser
      degree, receipt of vaccinations that would normally be attributed to educational
      attainment and/or race if literacy was not considered.

PMID- 16881948
TI  - Importance of adult literacy in understanding health disparities.
AB  - BACKGROUND: In several recent studies, the importance of education and race in
      explaining health-related disparities has diminished when literacy was
      considered. This relationship has not been tested in a nationally representative
      sample of U.S. adults. OBJECTIVE: To understand the effect of adult literacy on
      the explanatory power of education and race in predicting health status among
      U.S. adults. DESIGN: Using the 1992 National Adult Literacy Survey, logistic
      regression models predicting health status were estimated with and without
      literacy to test the effect of literacy inclusion on race and education.
      SUBJECTS: A nationally representative sample of 23,889 noninstitutionalized U.S.
      adults. MEASURES: Poor health status was measured by having a work-impairing
      condition or a long-term illness. Literacy was measured by an extensive
      functional skills test. RESULTS: When literacy was not considered, African
      Americans were 1.54 (95% confidence interval, 1.29 to 1.84) times more likely to
      have a work-impairing condition than whites, and completion of an additional
      level of education made one 0.75 (0.69 to 0.82) times as likely to have a work
      impairing condition. When literacy was considered, the effect estimates of both
      African-American race and education diminished 32% to the point that they were no
      longer significantly associated with having a work-impairing condition. Similar
      results were seen with long-term illness. CONCLUSIONS: The inclusion of adult
      literacy reduces the explanatory power of crucial variables in health disparities
      research. Literacy inequity may be an important factor in health disparities, and
      a powerful avenue for alleviation efforts, which has been mistakenly attributed
      to other factors.

PMID- 16881949
TI  - Use of a modified informed consent process among vulnerable patients: a
      descriptive study.
AB  - BACKGROUND: Little is known about patient characteristics associated with
      comprehension of consent information, and whether modifications to the consent
      process can promote understanding. OBJECTIVE: To describe a modified research
      consent process, and determine whether literacy and demographic characteristics
      are associated with understanding consent information. DESIGN: Descriptive study
      of a modified consent process: consent form (written at a sixth-grade level) read
      to participants, combined with 7 comprehension questions and targeted education,
      repeated until comprehension achieved (teach-to-goal). PARTICIPANTS: Two hundred
      and four ethnically diverse subjects, aged > or = 50, consenting for a trial to
      improve the forms used for advance directives. MEASUREMENTS: Number of passes
      through the consent process required to achieve complete comprehension. Literacy
      assessed in English and Spanish with the Short Form Test of Functional Health
      Literacy in Adults (scores 0 to 36). RESULTS: Participants had a mean age of 61
      years and 40% had limited literacy (s-TOHFLA<23). Only 28% of subjects answered
      all comprehension questions correctly on the first pass. After adjustment, lower
      literacy (P=.04) and being black (P=.03) were associated with requiring more
      passes through the consent process. Not speaking English as a primary language
      was associated with requiring more passes through the consent process in
      bivariate analyses (P<.01), but not in multivariable analyses (P>.05). After the
      second pass, most subjects (80%) answered all questions correctly. With a teach
      to-goal strategy, 98% of participants who engaged in the consent process achieved
      complete comprehension. CONCLUSIONS: Lower literacy and minority status are
      important determinants of understanding consent information. Using a modified
      consent process, little additional education was required to achieve complete
      comprehension, regardless of literacy or language barriers.

PMID- 16881950
TI  - Brief report: screening items to identify patients with limited health literacy
      skills.
AB  - BACKGROUND: Patients with limited literacy skills are routinely encountered in
      clinical practice, but they are not always identified by clinicians. OBJECTIVE:
      To evaluate 3 candidate questions to determine their accuracy in identifying
      patients with limited or marginal health literacy skills. METHODS: We studied 305
      English-speaking adults attending a university-based primary care clinic.
      Demographic items, health literacy screening questions, and the Rapid Estimate of
      Adult Literacy in Medicine (REALM) were administered to patients. To determine
      the accuracy of the candidate questions for identifying limited or marginal
      health literacy skills, we plotted area under the receiver operating
      characteristic (AUROC) curves for each item, using REALM scores as a reference
      standard. RESULTS: The mean age of subjects was 49.5; 67.5% were female, 85.2%
      Caucasian, and 81.3% insured by TennCare and/or Medicare. Fifty-four (17.7%) had
      limited and 52 (17.0%) had marginal health literacy skills. One screening
      question, "How confident are you filling out medical forms by yourself?" was
      accurate in detecting limited (AUROC of 0.82; 95% confidence interval [CI]=0.77
      to 0.86) and limited/marginal (AUROC of 0.79; 95% CI=0.74 to 0.83) health
      literacy skills. This question had significantly greater AUROC than either of the
      other questions (P<.01) and also a greater AUROC than questions based on
      demographic characteristics. CONCLUSIONS: One screening question may be
      sufficient for detecting limited and marginal health literacy skills in clinic
      populations.

PMID- 16881951
TI  - The meaning and the measure of health literacy.

PMID- 16881952
TI  - How health care systems can begin to address the challenge of limited literacy.

PMID- 16881954
TI  - Beyond the Institute of Medicine health literacy report: are the recommendations
      being taken seriously?

PMID- 16881953
TI  - Teaching about health literacy and clear communication.

PMID- 16881955
TI  - Improving literacy as a means to reducing health disparities.

PMID- 16881956
TI  - Literacy and health outcomes: is adherence the missing link?

PMID- 16881957
TI  - Confirming comprehension of informed consent as a protection of human subjects.

PMID- 16881959
TI  - Thrombin is bad, accepted; but is smoking good to prevent restenosis?

PMID- 16881960
TI  - Family secrets to be disclosed.

PMID- 16881962
TI  - Cancer-associated genodermatoses: a personal history.
AB  - Cancer-associated genodermatoses are a group of genetic disorders inherited in an
      autosomal-dominant fashion in which unique cutaneous findings are a reliable
      marker for the risk of developing internal malignancies. The historical, clinical
      and dermatopathological aspects of basal cell nevus syndrome, Muir-Torre
      syndrome, Cowden syndrome, Carney complex and Birt-Hogg-Dube syndrome are
      reviewed in a personal and informal fashion. The latest advances in the molecular
      genetics of the disorders are also summarized.

PMID- 16881963
TI  - Hedgehog signalling in skin development and cancer.
AB  - Basal cell carcinoma (BCC) is the most common human malignancy, affecting 750,000
      Americans each year. The understanding of mutations that are known to activate
      hedgehog (Hh) signalling pathway genes, including PATCHED (PTCH), sonic hedgehog
      (Shh) and smoothened (Smo), has substantially expanded our current understanding
      of the genetic basis of BCC development. The Hh signalling pathway is one of the
      most fundamental signal transduction pathways in embryonic development. In skin,
      the Shh pathway is crucial for maintaining stem cell population, and for
      regulating hair follicle and sebaceous gland development. This pathway plays a
      minimal role in adult tissues, but is known to be activated in many neoplasms,
      including those arising in the skin. In this review, we attempt to summarize the
      results of published studies on some important aspects of the Shh pathway and its
      involvement in skin development and carcinogenesis. We also provide a description
      of various animal models that have been developed, based on our knowledge of the
      Shh pathway in human skin cancers. Additionally, we include a brief description
      of studies conducted in our laboratory and by others on the chemoprevention of
      BCCs. This review therefore provides a current understanding of the role of the
      Shh pathway in skin development and neoplasia. It also provides a basis for the
      molecular target-based chemoprevention and therapeutic management of skin cancer.

PMID- 16881964
TI  - Botanical antioxidants in the prevention of photocarcinogenesis and photoaging.
AB  - Exposure of the skin to ultraviolet (UV) radiation, particularly its UV-B
      component (280-320 nm), from the sun results in erythema, edema, hyperplasia,
      hyperpigmentation, sunburn cells, immunosuppression, photoaging, and skin cancer.
      Amongst these various adverse effects of UV-B radiation, skin cancer and
      photoaging are of great concern. More recent changes in lifestyle have led to a
      significant increase in the amount of UV-B radiation people receive leading to a
      surge in the incidence of skin cancer and photoaging. As these trends are likely
      to continue in the foreseeable future, the adverse effect of UV-B has become a
      major human health concern. Therefore, development of novel strategies to reduce
      the occurrence of skin cancer and delay the process of photoaging are highly
      desirable goals. One approach to reduce their occurrence is through
      photochemoprevention, which we define as the use of agents capable of
      ameliorating the adverse effects of UV-B on the skin. Photochemoprevention via
      use of botanical antioxidants, present in the common diet of human have gained
      considerable attention as photochemopreventive agents for human use. Many such
      agents have also found a place in skin care products. This review will focus on
      the effects of selected botanical antioxidants in the prevention of
      photocarcinogenesis and photoaging.

PMID- 16881965
TI  - Dual porphyrias revisited.
AB  - The porphyrias are clinically and genetically heterogeneous metabolic diseases,
      which predominantly result from a hereditary dysfunction in the pathway of haeme
      biosynthesis. Currently, at least eight different forms of porphyrias can be
      differentiated, all of them characterized by a specific enzyme deficiency that is
      either inherited in an autosomal-dominant fashion, autosomal recessively or, in
      the case of porphyria cutanea tarda, might also be acquired. All genes encoding
      these enzymes have been cloned and several mutations underlying the different
      types of porphyrias have been reported. Traditionally, the diagnosis of porphyria
      is made on the basis of clinical symptoms, characteristic biochemical findings
      and enzyme assays. In some porphyria patients and families, however, these
      diagnostic tools can reveal simultaneous findings compatible with two different
      forms of porphyria, a phenomenon referred to as dual porphyria. Here, we give an
      overview on what is currently known about these peculiar variants of porphyria
      and suggest that, whenever feasible, molecular genetic analysis should complement
      the analytical techniques used to characterize patients and families in which a
      double enzymatic deficiency within the haeme biosynthetic pathway is assumed.

PMID- 16881966
TI  - Concepts in molecular dermatotoxicology.
AB  - In the recent years, molecular research has successfully elucidated some of the
      major mechanisms through which environmental noxae damage human skin. From this
      knowledge, novel concepts for skin protection have been developed. Here, we
      provide a brief overview of some of the most exciting and intriguing concepts in
      molecular dermatotoxicology.

PMID- 16881967
TI  - Dioxin-induced chloracne--reconstructing the cellular and molecular mechanisms of
      a classic environmental disease.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is among the most toxic pollutants
      known to date that serves as a prototype for a group of halogenated hydrocarbon
      compounds characterized by extraordinary environmental persistence and unique
      ability to concentrate in animal and human tissues. TCDD can elicit a complex
      array of pleiotropic adverse effects in humans, although chloracne, a specific
      type of acne-like skin disease, is the only consistent manifestation of dioxin
      intoxication, thus representing a 'hallmark' of TCDD exposure. Chloracne is
      considered to be one of the most specific and sensitive biomarkers of TCDD
      intoxication that allows clinical and epidemiological evaluation of exposure
      level at threshold doses. The specific cellular and molecular mechanisms involved
      in pathogenesis of chloracne are still unknown. In this review, we summarize the
      available clinical data on chloracne and recent progress in understanding the
      role of the dioxin-dependent pathway in the control of gene transcription and
      discuss molecular and cellular events potentially involved in chloracne
      pathogenesis. We propose that the dioxin-induced activation of skin stem cells
      and a shift in differentiation commitment of their progeny may represent a major
      mechanism of chloracne development.

PMID- 16881968
TI  - Recurring HRAS mutation G12S in Dutch patients with Costello syndrome.
AB  - Costello syndrome (CS) is a rare multiple congenital anomaly/mental retardation
      syndrome characterized by coarse face, loose skin and cardiomyopathy. It is often
      associated with benign and malignant tumors. Several groups have now demonstrated
      that CS is caused by recurring mutations in the HRAS gene in different ethnic
      groups. Here, we describe three unrelated Dutch patients and show that they all
      have the same mutation, G12S, in HRAS. To our knowledge, our patients are the
      first Dutch to be analysed. The syndrome seems to be genetically homogeneous. We
      discuss the pertinent nosology of the syndrome.

PMID- 16881969
TI  - Diffuse and segmental variants of cutaneous leiomyomatosis: novel mutations in
      the fumarate hydratase gene and review of the literature.
AB  - Multiple cutaneous and uterine leiomyomatosis (MCUL; OMIM 150800) is an autosomal
      dominantly inherited disease characterized by leiomyomas of the skin and uterine
      leiomyomas. Recently, association of MCUL with different forms of renal cancer
      has been described. This syndrome is referred to as hereditary leiomyomatosis and
      renal cell cancer (OMIM 605839). Both disorders result from heterozygous germline
      mutations in the fumarate hydratase (FH) gene that may function as a tumor
      suppressor. Interestingly, cutaneous leiomyomas do not only manifest in a diffuse
      and symmetric fashion. Rather frequently, a segmental or band-like manifestation
      pattern can be observed, usually following the lines of Blaschko. Here, we sought
      to elucidate the molecular basis of diffuse and segmental cutaneous
      leiomyomatosis in six unrelated Dutch and Spanish patients and their families. We
      identified six novel FH mutations, including one missense and one nonsense
      mutation, two deletions and two splice-site mutations. The segmental phenotype
      that was observed in various patients with FH mutations most likely reflects a
      type 2 segmental manifestation of cutaneous leiomyomatosis as previously also
      described for other autosomal dominantly inherited skin diseases. The results
      presented here extend the current data on the molecular basis of familial
      cutaneous leiomyomatosis and comprise, to the best of our knowledge, the first
      genetic study in Dutch and Spanish patients with this disorder. In addition, we
      review the clinical and molecular aspects of the disease.

PMID- 16881970
TI  - Long-term establishment, characterization and manipulation of cell lines from
      mouse basal cell carcinoma tumors.
AB  - There have been few reports of successful long-term culture of cells established
      from cutaneous basal cell carcinoma (BCC) tumors. Here, we describe techniques
      that have enabled us to establish three long-term cultures of BCC cells isolated
      from BCC tumors that arose in irradiated Patched 1 (Ptch1)(+/-) mice. All three
      cell lines showed cellular morphology similar to that of BCC tumors and could be
      propagated for at least 20 passages. In addition, similar to BCC tumors, all cell
      lines had lost the wildtype Ptch1 allele, expressed BCC molecular markers, and
      responded similarly to cyclopamine, a small molecule inhibitor of Hedgehog
      signaling. Finally, we describe an efficient electroporation technique for DNA
      transfection into the BCC cell lines and show that they have activated Hedgehog
      signaling activity, albeit at a level lower than that of murine BCCs in vivo.
      These data indicate that the cell lines are bona fide long-term cultures of BCC
      cells and that DNA plasmids can be introduced into the BCC cell lines with
      relatively high transfection efficiency using a modified electroporation
      technique.

PMID- 16881971
TI  - Does proximal location of culprit lesion confer worse prognosis in patients
      undergoing primary percutaneous coronary intervention for ST elevation myocardial
      infarction?
AB  - ST segment elevation myocardial infarction (STEMI) from proximally located
      culprit lesion is associated with greater myocardium at jeopardy. In STEMI
      patients treated with thrombolytics, proximal culprit lesions are known to have
      worse prognosis. This relation has not been studied in patients undergoing
      primary percutaneous coronary intervention (PCI). In 3,535 STEMI patients with
      native coronary artery occlusion pooled from the primary angioplasty in
      myocardial infarction database, we compared in-hospital and 1-year outcomes
      between those with proximal (n = 1,606) versus non-proximal (n = 1,929) culprit
      lesions. Patients with proximal culprits were more likely to die and suffer major
      adverse cardiovascular events (MACE) during the index hospital stay (3.8% vs
      2.2%, P = 0.006; 8.2% vs 5.8%, P = 0.0066, respectively) as well as during 1-year
      follow-up (6.9% vs 4.5%, P = 0.0013; 22% vs 17%, P = 0.003, respectively)
      compared to those with non-proximal culprits. After adjustment for baseline
      differences, proximal culprit was independently predictive of in-hospital death
      (adjusted odds ratio% 1.58, 95% confidence intervals, CI 1.05-2.40) and MACE (OR
      1.41, CI 1.06-1.86), but not 1-year death or MACE. In addition, proximal culprit
      was independently associated with higher incidence of ventricular arrhythmias and
      sustained hypotension during the index hospitalization. The univariate impact of
      proximal culprit lesion on in-hospital death and MACE was comparable to other
      adverse angiographic characteristics, such as multivessel disease and poor
      initial thrombolysis in myocardial infarction flow, and greater than that of
      anterior wall STEMI. In conclusion, proximal location of the culprit lesion is a
      strong independent predictor of worse in-hospital outcomes in patients with STEMI
      undergoing primary PCI.

PMID- 16881973
TI  - Stem cells show mixed results in MI patients.

PMID- 16881974
TI  - Myoblast cell therapy shows promise, but safety issues linger.

PMID- 16881975
TI  - Hybrid cell technologies show promise in treating ischemia.

PMID- 16881976
TI  - Sirolimus-eluting stent in chronic total occlusion: the SICTO study.
AB  - Coronary stenting can significantly reduce the restenosis and reocclusion rates
      after successful balloon angioplasty for chronic total occlusions (CTO).
      Nevertheless, recanalization of CTO remains among the worst predictors for in
      stent restenosis and reocclusion. This multicenter, nonrandomized study assessed
      the safety and effectiveness of the CYPHER sirolimus-eluting stent in reducing
      angiographic in-stent late loss in totally occluded native coronary arteries. A
      total of 25 eligible patients were treated with the CYPHER sirolimus-eluting
      stent. Baseline clinical and angiographic data were collected and 6-month follow
      up angiography and intravascular ultrasound (IVUS) were performed. Clinical
      follow-up was required at 30 days, 6, 12, 18, and 24 months. Study stent
      implantation was successful in all patients, with a mean stent length of 28.4 +/-
      11 mm. Six-month angiographic outcomes showed that mean lumen diameter stenosis
      did not change (2.22 +/- 0.56 mm postprocedure; 2.26 +/- 0.60 mm at 6 months
      follow-up; P = NS). Similarly, mean percent diameter stenosis did not change
      significantly (15.7 +/- 8.6% postprocedure, 19.3 +/- 11% at follow-up; P = NS).
      The absolute late lumen loss was -0.03 +/- 0.28 mm with a 6-month in-stent
      restenosis rate of 0%. IVUS follow-up revealed in-stent obstruction volume of
      only 4.9 +/- 6.8%. Long-term clinical follow-up showed target lesion
      revascularization at 12 months was only 4%, with target vessel revascularization
      of only 12%. The CYPHER sirolimus-eluting stent was safe and effective in the
      treatment of CTO compared to historical data with bare metal stents.

PMID- 16881977
TI  - "Do least harm" philosophy may suffice for percutaneous coronary intervention in
      octogenarians.
AB  - BACKGROUND: Octogenarians represent one of the most rapidly expanding segments of
      the population and an ever growing number are undergoing percutaneous coronary
      intervention (PCI). A simplified approach with incomplete or "culprit-lesion"
      only PCI may be an option even in multivessel disease, to minimize periprocedural
      complications while still allowing a meaningful clinical recovery in patients
      with inherent functional limitations related to age itself. We tried to determine
      the effects of either complete or partial PCI on procedural and long-term outcome
      in a consecutive series of octogenarians. METHODS: In-hospital and 1-year
      clinical outcomes were collected in elderly patients treated with PCI between
      January 1998 and March 2004 in our institution. RESULTS: In a total of 165
      octogenarians, 73 elderly patients (44%) underwent complete (COM) and 92 (56%)
      incomplete (INC) revascularization. Major in-hospital cardiac events were similar
      in the two subgroups. At 1-year follow-up 65% of patients in the COM and 68% in
      the INC group (P = ns) referred improvement in angina status and quality of life.
      Clinically driven repeat PCI was necessary in 16% of COM and 15% of INC patients.
      Recurrent PCI was mostly required to treat a restenotic index lesion in both
      groups, while only five patients in the INC group (5.4%) required PCI of a
      different lesion. CONCLUSIONS: Current PCI coronary techniques are safe and
      effective in octogenarians. Restenosis remains the main cause for recurrent
      events after bare metal stents. Percutaneous revascularization limited to the
      culprit lesion may suffice in most patients, with favorable clinical outcome at 1
      year.

PMID- 16881978
TI  - Alcohol septal ablation for hypertrophic obstructive cardiomyopathy: a systematic
      review of published studies.
AB  - OBJECTIVE: Alcohol septal ablation (ASA) for hypertrophic obstructive
      cardiomyopathy (HOCM) has emerged as a lesser invasive alternative to surgical
      myectomy over the past decade. The purpose of this study is to analyze all the
      published literature on outcomes and complications after ASA. METHODS: MEDLINE
      and PubMed were searched for all available published literature on ASA (June 1996
      June 2005) using the terms hypertrophic obstructive cardiomyopathy (HOCM),
      alcohol septal ablation for hypertrophic obstructive cardiomyopathy, alcohol
      septal ablation for HOCM, alcohol septal ablation (ASA), transcoronary alcohol
      septal ablation for hypertrophic obstructive cardiomyopathy (TASH), transcoronary
      alcohol septal ablation for HOCM, nonsurgical septal reduction therapy (NSRT),
      and percutaneous transcoronary septal myocardial ablation (PTSMA). RESULTS: A
      total of 42 published studies (2,959 patients) were analyzed. Mean age was 53.5
      (35.4-72) years with a mean male to female ratio of 1.17. Mean follow-up was 12.7
      +/- 0.3 months (1.5-43.2). Absolute ethanol (3 mL) was injected in 1.2 septal
      perforator arteries. On average, serum CK peaked at 964 units. At 12 months,
      there was a sustained decrease in resting and provoked LVOT gradient (65.3-15.8
      and 125.4-31.5 mmHg, respectively) accompanied by reduction in basal septal
      diameter (20.9-13.9 mm), improvement in NYHA Class (2.9-1.2), and increase in
      exercise capacity (325.3-437.5 seconds). Early mortality (within 30 days) was
      1.5% (0.0-5.0%) and late mortality (beyond 30 days) was 0.5% (0.0-9.3%). Other
      complications include ventricular fibrillation (2.2%), LAD dissection (1.8%),
      complete heart block requiring permanent pacemaker (10.5%), and pericardial
      effusion (0.6%). A repeat ASA was performed on 6.6% of patients and 1.9% of
      patients underwent surgical myomectomy with resolution of symptoms. CONCLUSIONS:
      Literature to date suggests that ASA results in acute and intermediate-term
      favorable clinical and echocardiographic outcomes. A randomized controlled trial
      is needed to compare ASA and myomectomy in order to determine which technique
      provides maximal benefit.

PMID- 16881979
TI  - Patent foramen ovale using the Premere device: the results of the CLOSEUP trial.
AB  - OBJECTIVES: The CLOSEUP trial was conducted to determine the safety and
      effectiveness of the Premere closure device in closure of patent foramen ovale
      (PFO). BACKGROUND: PFO is a relatively common congenital condition, associated
      with cryptogenic stroke and migraine with aura. The Premere device is
      specifically designed to close PFO of variable size and length, with right and
      left anchor arms connected by a flexible tether. The device has an open
      architecture, a low profile, and a small surface area on the left atrial side
      which may discourage thrombus formation. METHODS: Patients between 18 and 65
      years of age who had a cryptogenic ischemic stroke or a transient ischemic attack
      and a PFO underwent percutaneous PFO closure using the Premere device. RESULTS:
      Of the 73 enrolled patients, six patients had atrial anatomy not appropriate for
      the Premere; 27 patients received the 15 mm and 40 patients received the 20 mm
      device. Implantation was successful in all patients. At 6 months of follow-up,
      86% of patients had no shunt that could be provoked with Valsalva as assessed
      during contrast echocardiography. Closure rates were better with the 20 mm versus
      the 15 mm device, and three patients with residual shunt had atrial septal
      aneurysms at baseline. One patient had transient atrial fibrillation which
      resolved by 3 months. There were no instances of thrombus, death, or stroke.
      CONCLUSIONS: These data demonstrate that the Premere device can safely and
      effectively close PFO. Additional studies should be undertaken to demonstrate the
      effectiveness of PFO closure in reducing thrombo-embolic events such as stroke.

PMID- 16881980
TI  - New technique for fenestration of the interatrial septum.
AB  - Achieving controlled flow between the systemic and pulmonary venous circulations
      is desirable in many complex congenital heart diseases. This includes the Fontan
      circulation, primary pulmonary hypertension, double inlet ventricles, or
      hypoplastic left heart with obstruction to the atrioventricular valve. As no
      specific device is available for this purpose, we developed a balloon-mounted
      stent technique to achieve a predetermined-sized fenestration of an atrial baffle
      in a patient with Fontan circulation. The details of the technique are described.

PMID- 16881981
TI  - IVUS makes important strides in 2005.
AB  - Researchers utilized intravascular ultrasound in unique ways in 2005, from
      assessing transplant vasculopathy to evaluating long-term drug-eluting stent
      outcomes to identifying predictors of stent thrombosis. These and other
      applications signify key developments in the field of intravascular imaging.

PMID- 16881982
TI  - The impact of gender on vessel size in patients with angiographically normal
      coronary arteries.
AB  - INTRODUCTION: Female gender has been associated with worse clinical outcomes
      following coronary revascularization. Whether a gender-specific difference in
      vessel size is contributing to this finding remains controversial. We sought to
      better define the relationship between gender and coronary artery size. METHODS:
      Baseline characteristics were obtained and quantitative coronary angiography was
      performed on 145 consecutive patients with angiographically normal (smooth
      luminal surface with no evidence of any irregularity in the coronary tree)
      coronary arteries. Two separate orthogonal measurements each were taken of the
      left main, proximal left anterior descending, proximal circumflex, proximal right
      coronary artery, and ostial posterior descending arteries. An average coronary
      size, derived from five separate coronary artery measurements, was tabulated for
      each patient. RESULTS: After correcting for confounding variables, including BSA,
      height, diabetes, and left ventricular hypertrophy using multivariate linear
      regression, female gender remained a strong independent predictor of coronary
      vessel size (Beta =-0.30, P = 0.004). Female gender was associated with a 0.30 mm
      decrease in average coronary size. CONCLUSION: Gender is a strong, independent
      predictor of coronary artery size even when taking into account differences in
      body size. This difference may contribute to worse outcomes of women undergoing
      coronary revascularization.

PMID- 16881983
TI  - Studying coronary plaque regression with IVUS.

PMID- 16881984
TI  - Does diagnostic coronary angiography induce significant coronary
      microembolization in stable, ischemic patients? A prospective study.
AB  - BACKGROUND: Although microembolization during percutaneous coronary interventions
      is a frequent event, the extent of possible microembolization during diagnostic
      coronary angiography is unknown. The aim of the study was to investigate whether
      diagnostic coronary angiography results in coronary microembolization and
      consequent subtle, subclinical myocardial necrosis with enzyme elevations.
      METHODS: Fifty-three consecutive patients underwent diagnostic coronary
      angiography due to inducible ischemia. Creatine kinase MB isoenzyme (CK MB) and
      cardiac troponin I (cTnI) were used as sensitive surrogate markers of myocardial
      necrosis. Serial measurements, before, and 6 and 24 hours following a diagnostic
      procedure, were performed. RESULTS: Baseline cTnI was below the limits of
      detection in all patients (<0.20 ng/mL), except for one patient with 1.31 ng/mL.
      Baseline median CK-MB was 1.05 ng/mL (interquartile range, 0.80-1.56 ng/mL) (Fig.
      1). Both at 6 and 24 hours, no patients had any increase in cTnI, with the
      exception of a minor increase to 0.22 ng/mL at 24 hours in one patient. At 6
      hours, 25 patients had decreases in CK MB, while 22 had increases (exact P =
      0.77). At 24 hours, 26 patients had decreases in CK MB and 19 patients had
      increases. CONCLUSIONS: Detectable embolization with subsequent subclinical
      myonecrosis is an unlikely event.

PMID- 16881985
TI  - When size matters: lessons learned from left main stent embolization and
      retrieval.
AB  - While the advantages of drug-eluting stents (DES) have been demonstrated in
      moderate and small-sized vessels, the benefits of DES use in selected larger
      vessels are increasingly recognized. In the following case presentation, the use
      of a DES outside the approved vessel diameter to treat left main coronary artery
      disease led to retrograde migration of the stent over the guiding catheter.
      Solutions to capturing and retrieving a stent in this position are discussed and
      our approach to resolving the situation is presented.

PMID- 16881986
TI  - Alveolar hemorrhage: an underdiagnosed complication of treatment with
      glycoprotein IIb/IIIa inhibitors.
AB  - OBJECTIVE: Alveolar hemorrhage (AH) is a rare complication of treatment with GP
      IIb/IIIa inhibitors. Hemoptysis, a constant sign, lacks in specificity, and may
      occur in confounding syndromes such as pulmonary edema, pulmonary infarction, and
      pneumonia. Nonspecific symptoms and signs often delay the diagnosis, thereby
      allowing serious or even fatal disease progression. Here, we performed a large
      scale retrospective analysis to define the incidence and risk factors of AH in
      the setting of GP IIb/IIIa inhibitors therapy. BACKGROUND: Randomized controlled
      trials demonstrate that treatment with glycoprotein IIb/IIIa (GP IIb/IIIa)
      inhibitors may improve the outcome of acute myocardial infarction (AMI) and
      angioplastic procedures. However, this treatment may rarely lead to severe
      hemorrhagic complications, in particular AH. Unfortunately, the incidence and
      risk factors of AH remain poorly defined. METHODS: We reviewed for the period
      extending from August 1998 to January 2005 consecutive histories of AMI patients
      receiving coronary arteriography and treatment with either eptifibatide or
      abciximab. Concomitantly admitted AMI patients not treated with GP IIb/IIIa
      inhibitors were reviewed and served as a control group. The diagnosis of AH
      required the demonstration of typical symptoms and signs including dyspnea,
      hemoptysis, arterial hypoxemia, pulmonary radiographic changes, and, when
      available, bronchoscopic signs for AH. Potential covariates including pulmonary
      disease, pulmonary hypertension, smoking, and use of other anticoagulant or
      antiplatelet agents were evaluated. RESULTS: Six of 1,810 patients (0.33%)
      receiving eptifibatide and five of 3,648 patients (0.14%) receiving abciximab
      exhibited typical symptoms and signs of AH. Contrarily, only one of 4,136
      patients (0.025%) receiving no GP IIb/IIIa inhibitors presented with similar
      symptoms and signs. There was no fatal outcome, though two patients required
      blood transfusions. Statistically significant differences were found between
      control patients and patients receiving eptifibatide alone (P = 0.004). There was
      also a significant difference between untreated patients and those receiving
      eptifibatide and abciximab (P = 0.017). No differences were found between
      eptifibatide and abciximab-treated patients (P = 0.19) or between abciximab and
      untreated control patients (P = 0.105). CONCLUSIONS: AH is a rare complication of
      treatment with GP IIb/IIIa inhibitors. Its incidence ranged from 0.14% in
      patients treated with abciximab to 0.33% in those receiving eptifibatide.
      Compared to a control group, patients treated with GP IIb/IIIa inhibitors had a
      statistically increased risk for AH.

PMID- 16881987
TI  - Skilled peer review: a road map to stronger scholarship.

PMID- 16881989
TI  - A randomized control trial of continuous support in labor by a lay doula.
AB  - OBJECTIVE: To compare labor outcomes in women accompanied by an additional
      support person (doula group) with outcomes in women who did not have this
      additional support person (control group). DESIGN: Randomized controlled trial.
      SETTING: A women's ambulatory care center at a tertiary perinatal care hospital
      in New Jersey. PATIENTS/PARTICIPANTS: Six hundred nulliparous women carrying a
      singleton pregnancy who had a low-risk pregnancy at the time of enrollment and
      were able to identify a female friend or family member willing to act as their
      lay doula. INTERVENTIONS: The doula group was taught traditional doula supportive
      techniques in two 2-hour sessions. MAIN OUTCOME MEASURES: Length of labor, type
      of delivery, type and timing of analgesia/anesthesia, and Apgar scores. RESULTS:
      Significantly shorter length of labor in the doula group, greater cervical
      dilation at the time of epidural anesthesia, and higher Apgar scores at both 1
      and 5 minutes. Differences did not reach statistical significance in type of
      analgesia/anesthesia or cesarean delivery despite a trend toward lower cesarean
      delivery rates in the doula group. CONCLUSION: Providing low-income pregnant
      women with the option to choose a female friend who has received lay doula
      training and will act as doula during labor, along with other family members,
      shortens the labor process.

PMID- 16881988
TI  - A systems approach for neonatal hyperbilirubinemia in term and near-term
      newborns.
AB  - OBJECTIVE: To propose and implement a family-centered systems approach to manage
      newborn jaundice for safer outcomes. DESIGN: Observational study for known
      adverse outcomes. SETTING: Semiprivate urban birthing hospital.
      PATIENTS/PARTICIPANTS: 31,059 well babies discharged as healthy from a cohort of
      41,961 live births (1990-2000). INTERVENTIONS: Incremental implementation of a
      systems approach that incorporated a hospital policy to (a) authorize nurses to
      obtain a bilirubin (total serum/transcutaneous) measurement for clinical
      jaundice, (b) universal predischarge total serum bilirubin (at routine metabolic
      screening), and (c) targeted follow-up, using the bilirubin nomogram (hour
      specific, percentile-based total serum bilirubin/transcutaneous bilirubin). MAIN
      OUTCOME MEASURES: Known adverse outcomes assessed for early- and late-onset
      severe hyperbilirubinemia before, during, and after systems approach
      implementation. RESULTS: Adverse outcomes decreased for well babies: exchange
      transfusion, intensive phototherapy, and readmission. During the study period,
      there were no "never events" (total serum bilirubin greater than or equal to 30
      mg/dl), while "close calls" (total serum bilirubin greater than or equal to 25
      mg/dl) were 1 in 15,000 as compared to a reported incidence of 1 in 625.
      CONCLUSIONS: Reduced adverse events, significant reduction in close calls, and no
      never events met family expectations for safer experiences with this approach.

PMID- 16881990
TI  - Water aerobics reduces sick leave due to low back pain during pregnancy.
AB  - OBJECTIVE: To compare the effect of a land-based, physical exercise program
      versus water aerobics on low back or pelvic pain and sick leave during pregnancy.
      DESIGN: Randomized controlled clinical trial. SETTING: Three antenatal care
      centers. PARTICIPANTS: 390 healthy pregnant women. INTERVENTIONS: A land-based
      physical exercise program or water aerobic once a week during pregnancy. MAIN
      OUTCOME MEASURES: Sick leave, pregnancy-related low back pain or pregnancy
      related pelvic girdle pain, or both. RESULTS: Water aerobics diminished pregnancy
      related low back pain (p=.04) and sick leave due to pregnancy-related low back
      pain (p=.03) more than a land-based physical exercise program. CONCLUSIONS: Water
      aerobics can be recommended for the treatment of low back pain during pregnancy.
      The benefits of a land-based physical exercise program are questionable and
      further evaluation is needed.

PMID- 16881992
TI  - Cardiovascular risk factors among Native American women Inter-Tribal Heart
      Project participants.
AB  - OBJECTIVE: To examine cardiovascular disease risk factors among adult Native
      American women Inter-Tribal Heart Project participants. DESIGN: A secondary
      analysis used controllable risk factors identified by the American Heart
      Association as the framework to examine cardiovascular disease risk factors in
      this population. SETTING: Three Native American Reservations in Minnesota and
      Wisconsin. PARTICIPANTS: 866 adult Native American women who participated in the
      Inter-Tribal Heart Project cardiovascular health research study. MAIN OUTCOME
      MEASURES: Descriptive, correlational, bivariate, and multivariate analysis
      provided findings on cardiovascular disease risk factors in this population.
      RESULTS: Cardiovascular disease risk factors are high among this population. For
      every additional risk factor, the odds of self-reported cardiovascular disease
      increases 1.2 times (95% confidence interval: 1.1-1.3). Participants who self
      reported cardiovascular disease were older, less educated, employed less, and
      reported more Indian ancestry (higher blood quantum) and had higher prevalence
      rates of diabetes, higher systolic blood pressure, and body mass index in
      comparison to women who self-reported an absence of cardiovascular disease.
      CONCLUSIONS: A key to decreasing cardiovascular disease lies in preventing and
      controlling cardiovascular disease risk factors with concerted efforts specific
      to the culture and life ways of the Native American woman.

PMID- 16881991
TI  - Trajectory of weight changes in the first 6 weeks postpartum.
AB  - OBJECTIVE: To determine the trajectory of postpartum weight changes and to
      examine associations between weight change in the first 6 weeks postpartum and
      demographic, clinical, psychosocial, and behavioral variables. DESIGN:
      Prospective, longitudinal design. SETTING: Community hospital and university
      research setting. PARTICIPANTS: 26 low-income women (9 White, 8 Black, and 9
      Hispanic) with uncomplicated term pregnancies. MAIN OUTCOME MEASURE: Body mass
      index measured weekly. RESULTS: Among White women, body mass index decreased
      significantly for the first 3 weeks of the postpartum period. Black women
      experienced a significant reduction in body mass index for only the first 2
      postpartum weeks. Similarly, the postpartum body mass index decreased for the
      first 2 weeks for Hispanic women. Prepregnancy body mass index and gestational
      weight gain each had a significant positive effect on postpartum body mass index.
      Perception of social support at 4 weeks had a significant positive effect on
      postpartum body mass index in Black women. CONCLUSIONS: The trajectory of weight
      change was nonlinear with large initial weight losses during the first 2 to 3
      weeks postpartum followed by weight plateaus for the remainder of the first 6
      weeks postpartum.

PMID- 16881993
TI  - Prevalence of antenatal depression in women enrolled in an outreach program in
      Canada.
AB  - OBJECTIVE: To determine the prevalence of depression and its correlates in
      pregnancy and to establish the appropriateness of using the Edinburgh Postnatal
      Depression Scale with inner-city, high-risk pregnant women. DESIGN: Convenience
      sample of women enrolled in a prenatal outreach program. Women were recruited and
      the Edinburgh Postnatal Depression Scale was administered during home visits.
      PARTICIPANTS: 39 women, most of whom were Aboriginal, participating in a prenatal
      outreach program. MAIN OUTCOME MEASURE: Edinburgh Postnatal Depression Scale
      score of >or=10 suggests minor depressive symptoms and >or=13 suggests probable
      major depression. RESULTS: 27% of women reported symptoms consistent with major
      depression. The Aboriginal women had higher levels of depressive symptoms than
      the non-Aboriginal women. Women who had stopped using tobacco or alcohol during
      pregnancy had more depressive symptoms than those who had quit before pregnancy.
      Acceptability of the Edinburgh Postnatal Depression Scale for use with high-risk,
      Aboriginal, and non-Aboriginal pregnant women was supported. CONCLUSIONS: The
      prevalence of depressive symptoms and concurrent substance use within this
      population is a major public health problem. Nurses can incorporate the Edinburgh
      Postnatal Depression Scale into routine prenatal visits to identify women at risk
      for depression.

PMID- 16881994
TI  - Severity of drug use, initiation of prenatal care, and maternal-fetal attachment
      in pregnant marijuana and cocaine/heroin users.
AB  - OBJECTIVE: To compare the severity of drug use, initiation of prenatal care, and
      maternal-fetal attachment between pregnant marijuana and cocaine/heroin users.
      DESIGN: A cross-sectional design. SETTING: A prenatal clinic of a medical center
      in the northeast of the United States. PARTICIPANTS: 19 marijuana, 17 cocaine,
      and 4 heroin users. Cocaine and heroin users were combined in one group. MAIN
      OUTCOME MEASURES: The Severity of Drug Use Questionnaire containing 11 questions
      of withdrawal, dependence, and medical, legal, and interpersonal issues was used
      to assess the severity of drug use. Initiation of prenatal care was obtained from
      the chart and was calculated by weeks of gestation when care began. Cranley's
      Maternal-Fetal Attachment Scale measured maternal-fetal attachment. RESULTS:
      Pregnant cocaine/heroin users were 6 years older, had experienced more
      pregnancies, had higher drug severity scores, and initiated prenatal care later
      than marijuana users. No significant difference in maternal-fetal attachment was
      found. CONCLUSION: Interventions to help especially cocaine/heroin users initiate
      early prenatal care and reduce severity of drug use are indicated.

PMID- 16881995
TI  - Deciding when it's labor: the experience of women who have received antepartum
      care at home for preterm labor.
AB  - OBJECTIVE: To describe how women who had received antepartum care at home for
      preterm labor managed subsequent episodes of preterm labor symptoms. DESIGN:
      Grounded theory method. SETTING: 2 Canadian antepartum home care programs.
      PARTICIPANTS: 12 women who received antepartum care at home for preterm labor
      that had been diagnosed in hospital prior to 34 weeks gestation. RESULTS: The
      core psychosocial process was reconciling body knowledge and professional
      knowledge. Study participants reported knowing something's not right and followed
      decision guides to seek help. If, when they returned to the hospital to see
      what's going on, they felt dissonance between what their bodies were telling them
      (body knowledge) and what their health care providers were telling them
      (professional knowledge) an overriding tension developed between not wanting to
      take a risk for the baby versus not wanting to overreact. These women
      reestablished their baselines of nonthreatening symptoms at a higher level by
      setting a new normal to avoid the humiliation associated with appearing to
      overreact. Attempting to ignore recurring symptoms of preterm labor delayed help
      seeking and caused anxiety. CONCLUSIONS: To avoid delayed help seeking, nursing
      interventions should be geared to reducing anxiety and validating the experiences
      of women with recurring preterm labor symptoms.

PMID- 16881996
TI  - Evaluation of the accuracy of height assessment of premenopausal and menopausal
      women.
AB  - OBJECTIVE: To assess the accuracy of linear measurement of premenopausal and
      menopausal women. DESIGN: Observational. SETTING: OB/GYN practice in a university
      setting. PARTICIPANTS: OB/GYN staff responsible for obtaining linear
      measurements. MAIN OUTCOME MEASURES: Equipment utilized, technique for obtaining
      linear measurement, accuracy of linear measurement. RESULTS: A research assistant
      observed six measurers measuring 64 women. Ninety four percent of measurements
      were inaccurate (p<.001) when compared to those of the research assistant.
      Measurements differed by as much as 18 cm from the research assistant (M=6.4 cm).
      Measurements obtained by measurers with more than 10 years of experience were
      significantly closer to the research assistant measurements than those obtained
      by less experienced measurers. CONCLUSIONS: Inaccurate equipment, incorrect
      technique, and staff inexperience all contributed significantly to inaccuracy of
      linear measurement in a GYN practice. Correct equipment and staff education are
      needed. Accurate linear measurements must be obtained to allow for valid clinical
      decisions regarding the need for hormone replacement therapy based on loss of
      stature of menopausal women.

PMID- 16881997
TI  - Web-based resources for health care providers and women following pregnancy loss.
AB  - Experiencing perinatal loss can leave women and families feeling distressed,
      overwhelmed, and with many questions, while health care providers often lack time
      and may not be prepared to provide all the answers. This paper highlights the
      rationale for use and benefits of the Internet with this population and outlines
      an effort to review and select reliable Internet resources containing valid and
      substantial content specific to pregnancy loss. A summary table is included for
      distribution to women and providers.

PMID- 16882000
TI  - Communication and teamwork in patient care: how much can we learn from aviation?
AB  - OBJECTIVE: To identify evidence on the role of assertiveness and teamwork and the
      application of aviation industry techniques to improve patient safety for
      inpatient obstetric care. DATA SOURCES: Studies limited to research with humans
      in English language retrieved from CINAHL, PubMed, Social Science Abstracts, and
      Social Sciences Citation Index, and references from reviewed articles. STUDY
      SELECTION: A total of 13 studies were reviewed, including 5 studies of teamwork,
      communication, and safety attitudes in aviation; 2 studies comparing these
      factors in aviation and health care; and 6 studies of assertive behavior and
      decision making by nurses. Studies lacking methodological rigor or focusing on
      medication errors and deviant behavior were excluded. DATA SYNTHESIS: Pilot
      attitudes regarding interpersonal interaction on the flight deck predicted
      effective performance and were amenable to behavior-based training to improve
      team performance. Nursing knowledge was inconsistently accessed in decision
      making. Findings regarding nurse assertiveness were mixed. CONCLUSIONS:
      Adaptation of training concepts and safety methods from other fields will have
      limited impact on perinatal safety without an examination of the contextual
      experiences of nurses and other health care providers in working to prevent
      patient harm.

PMID- 16882001
TI  - Nurse-physician communication during labor and birth: implications for patient
      safety.
AB  - OBJECTIVE: To describe communication between nurses and physicians during labor
      within the context of the nurse-managed labor model in community hospitals and
      its relationship to teamwork and patient safety. DESIGN: Multicenter qualitative
      study involving focus groups and in-depth interviews. SETTING: Labor and birth
      units in 4 Midwestern community hospitals. PARTICIPANTS: 54 labor nurses and 38
      obstetricians. METHODS: Focus groups and in-depth interviews were conducted using
      open-ended questions. Data were analyzed using inductive coding methods to gain
      understanding from the perspective of those directly involved. MAIN OUTCOME
      MEASURES: Description of interdisciplinary interactions during labor. RESULTS:
      Nurses and physicians shared the common goal of a healthy mother and baby but did
      not always agree on methods to achieve that goal. Two clinical situations
      critical to patient safety (fetal assessment and oxytocin administration) were
      frequent areas of disagreement and sources of mutual frustration, often leading
      to less than optimal teamwork. Minimal communication occurred when the mother and
      fetus are doing well, and this seemed to be purposeful and considered normal.
      Physicians and nurses had distinct opinions concerning desirable traits of
      members of the other discipline. CONCLUSIONS: Interdisciplinary communication and
      teamwork could be improved to promote a safer care environment during labor and
      birth.

PMID- 16882002
TI  - Improving patient safety with team coordination: challenges and strategies of
      implementation.
AB  - The health care environment presents significant risk of errors leading to
      patient injury and harm. One method to promote patient safety involves improving
      team coordination. The MedTeams training program, a nationally funded research
      project, provided the framework for team training in several labor and delivery
      units in the United States. Many challenges were confronted when team training
      was implemented. Based on these experiences, specific strategies to ensure the
      success of team training are discussed.

PMID- 16882003
TI  - Evidence for the involvement of purinergic P2X receptors in outer retinal
      processing.
AB  - Extracellular ATP mediates fast excitatory neurotransmission in many regions of
      the central nervous system through activation of P2X receptors. Although several
      P2X receptor subunits have been identified in the mammalian retina, little is
      known about the functional role of these receptors in retinal signalling. The
      purpose of the present study was to investigate whether purinergic P2X(7)
      receptors are involved in outer retinal processing by assessing receptor
      localization, degradation of extracellular ATP and the effect of functional
      activation of P2X(7) receptors on the electroretinogram (ERG). Using light and
      electron microscopy, we demonstrated that P2X(7) receptors are expressed
      postsynaptically on horizontal cell processes as well as presynaptically on
      photoreceptor synaptic terminals in both the rat and marmoset retina. Using an
      enzyme cytochemical method, we showed that ecto-ATPases are active in the outer
      plexiform layer of the rat retina, providing a mechanism by which purinergic
      synaptic transmission can be rapidly terminated. Finally, we evaluated the role
      of P2X(7) receptors in retinal function by assessing changes to the ERG response
      of rats after intravitreal delivery of the P2X(7) receptor agonist benzoyl
      benzoyl ATP (BzATP). Intravitreal injection of BzATP resulted in a sustained
      increase (up to 58%) in the amplitude of the photoreceptor-derived a-wave of the
      ERG. In contrast, BzATP caused a transient reduction in the rod- and cone-derived
      postreceptoral responses. These results provide three lines of evidence for the
      involvement of extracellular purines in outer retinal processing.

PMID- 16882004
TI  - The cytoplasmic domain of NrCAM binds to PDZ domains of synapse-associated
      proteins SAP90/PSD95 and SAP97.
AB  - NrCAM, a member of the L1 family of cell adhesion molecules, serves important
      functions during the development of the nervous system, e.g. in adhesion
      dependent processes such as neurite outgrowth and axonal pathfinding. Complex
      homo- and heterophilic binding and several extracellular ligands of NrCAM have
      been described, but less is known about intracellular interaction partners. The
      cytoplasmic carboxy-terminus of NrCAM contains a typical sequence motif for
      binding to PDZ domains, making interactions with PDZ domain-containing
      scaffolding proteins quite conceivable. In this study, we identified specific
      interactions of the intracellular domain of NrCAM with class I PDZ domains of the
      membrane-associated guanylate kinases SAP90/PSD95 and SAP97. In contrast to
      NrCAM, the intracellular domains of the other mammalian L1 family molecules, e.g.
      L1, CHL1 and Neurofascin, did not interact with these PDZ domains. In transfected
      COS-7 cells, NrCAM-mediated recruitment of SAP97 to the plasma membrane was
      dependent on the PDZ binding motif. We show that NrCAM and SAP97 are colocalized,
      e.g. within photoreceptor terminals of the mammalian retina. In summary, our
      results confirm a functional PDZ domain binding motif at the carboxy-terminus of
      NrCAM and support potential functions of NrCAM during the assembly of highly
      organized protein complexes at the cell membrane.

PMID- 16882005
TI  - Uncoupling protein-2 promotes nigrostriatal dopamine neuronal function.
AB  - Uncoupling protein 2 (UCP2) is known to promote neuroprotection in many forms of
      neurological pathologies including Parkinson's disease. Here, we examined the
      hypothesis that UCP2 also mediates aspects of normal nigrostriatal dopamine (DA)
      function. Mice lacking UCP2 exhibited reduced dopamine turnover in the striatum
      as measured by the 3,4-dihydoxyphenylacetic acid/dopamine (DOPAC/DA) ratio,
      reduced tyrosine hydroxylase immunoreactivity (TH IR) in the substantia nigra
      pars compacta (SNc) and reticulata, striatum and nucleus accumbens. UCP2-knockout
      (KO) mice also had reduced dopamine transporter immunoreactivity (DAT IR) in the
      SNc but not other brain regions examined. In order to determine if these
      biochemical deficits are transcribed into behavioural deficits, we examined
      locomotor function in UCP2-KO mice compared to wild-type (WT) controls. UCP2-KO
      mice exhibited significantly reduced total movement distance, movement velocity
      and increased rest time compared to wild-type controls. These results suggest
      that UCP2 is an important mitochondrial protein that helps to maintain normal
      nigrostriatal dopamine neuronal function and a reduction in UCP2 levels may
      predispose individuals to environmental causes of Parkinson's disease.

PMID- 16882006
TI  - Expression of Drosophila BarH1-H2 homeoproteins in developing dopaminergic cells
      and segmental nerve a (SNa) motoneurons.
AB  - Barh1/h2 genes encode two related homeobox transcription factors (B-H1 and B-H2)
      previously shown to play essential roles in the formation and specification of
      the distal leg segments and in retinal neurogenesis. Here we describe the
      restricted expression pattern of the B-H1/-H2 homeoprotein within the embryonic
      ventral nerve cord of Drosophila. We show that B-H1/-H2 are specifically
      expressed in a subset of dopaminergic neurons, namely the unpaired ventral
      midline dopaminergic neuron, and in a subpopulation of laterally projecting
      motoneurons, i.e. the five motoneurons forming the segmental nerve a (SNa)
      branch. Using the GAL4-UAS system we show that B-H1/-H2(Gal4) in combination with
      a membrane-targeted enhanced green fluorescent protein reporter line provides a
      powerful genetic tool reproducibly to label SNa motoneuron projections and
      terminals at the periphery, and their dendritic tree in the ventral nerve cord.
      Thus, the highly restricted expression pattern of the B-H1/-H2 homeoproteins and
      notably the related Gal4 driver represent powerful genetic tools to identify and
      study genes that control axon guidance, synaptogenesis or dendritic arborization
      within a small subpopulation of motoneurons identifiable from embryogenesis to
      late larval stages.

PMID- 16882007
TI  - Insulin-like growth factor-1 is an endogenous mediator of focal ischemia-induced
      neural progenitor proliferation.
AB  - The adult mammalian brain contains resident neural progenitors in the subgranular
      zone of the dentate gyrus (DG) and the subventricular zone (SVZ) of the lateral
      ventricles. The proliferation of neural progenitors increases after focal
      cerebral ischemia in both of these regions, but the mechanisms that promote
      ischemia-induced neural progenitor proliferation are not yet understood. We
      hypothesize that diffusible factors from the ischemic area play a role in this
      process as the DG is remote from the area of infarction. In this study, we
      observed that the peak of neural progenitor proliferation in the ipsilateral DG
      was between day 2 and day 4 of reperfusion after transient middle cerebral artery
      occlusion in adult spontaneously hypertensive rats. GeneChip and real-time PCR
      analysis showed a three- to 102-fold increase in the expression of 15 diffusible,
      mitogenic factors in the ischemic cortex at 3 days of reperfusion. Of these,
      insulin-like growth factor-1 (IGF-1) showed increased protein expression in the
      activated astrocytes in the ischemic penumbra. In addition, the progenitors in
      both the SVZ and DG showed IGF-1 receptor expression. Inhibiting IGF-1 activity
      by introcerebroventricular infusion of IGF-1 antibody significantly prevented the
      ischemia-induced neural progenitor proliferation. These results indicate that IGF
      1 formed in the ischemic penumbra might be one of the diffusible factors that
      mediate post-ischemic neural progenitor proliferation.

PMID- 16882008
TI  - Modulation of the trafficking of the human serotonin transporter by human alpha
      synuclein.
AB  - alpha-Synuclein (alpha-Syn), a protein primarily localized in the presynaptic
      compartment of neurons, is known to regulate dopaminergic neurotransmission by
      negatively modulating dopamine transporter activity and regulating its
      trafficking to or away from the cell surface. Given the considerable homology
      between dopamine transporters and the serotonin (5-HT) transporter (SERT), we
      examined whether alpha-Syn could similarly regulate SERT function. Increasing
      expression levels of human alpha-Syn gradually decreased [(3)H]5-HT uptake by
      human SERT in cotransfected Ltk(-) cells, by diminishing its V(max) without
      changing its K(m), as compared to cells expressing only SERT. Biotinylation
      studies to label cell-surface proteins showed that alpha-Syn decreased the levels
      of SERT present at the plasma membrane. alpha-Syn and SERT were able to
      coimmunoprecipitate (co-IP), suggesting heteromeric complexes between these two
      proteins through direct protein-protein interactions. The negative modulation of
      SERT activity by alpha-Syn occurred through the non-Abeta-amyloid component (NAC)
      domain of alpha-Syn (aa58-107); DNA constructs encoding this region mimicked the
      full-length alpha-Syn protein by decreasing [(3)H]5-HT uptake by the transporter.
      Furthermore, only the constructs encoding the NAC domain of alpha-Syn prevented
      the co-IPs between full-length alpha-Syn and SERT, in both transfected cells and
      in rat solubilized lysates isolated from the prefrontal cortex. These studies
      suggest a novel physiological role for alpha-Syn in regulating SERT activity and
      may be of relevance in certain mental illnesses and in depression, in which SERT
      function is believed to be dysregulated.

PMID- 16882009
TI  - Brain cytokine synthesis induced by an intraparenchymal injection of LPS is
      reduced in MCP-1-deficient mice prior to leucocyte recruitment.
AB  - We have previously shown that ischaemic lesions are smaller in monocyte
      chemoattractant protein-1-deficient (MCP-1(-/-)) mice than in wild-type (wt)
      controls. In addition to its role as a monocyte chemoattractant, monocyte
      chemoattractant protein-1 (MCP-1) has been proposed to contribute to lesion
      progression after focal ischaemia by driving local cytokine synthesis by resident
      glia. To investigate this hypothesis we injected lipopolysaccharide (LPS) into
      the brain parenchyma of MCP-1(-/-) mice and compared the resulting inflammatory
      response and production of proinflammatory cytokines to those in wt mice.
      Microglial and astrocyte morphological activation was the same in the two
      strains, but MCP-1(-/-) mice showed significantly lower levels of proinflammatory
      cytokine synthesis; interleukin-1beta (IL-1beta) and tumour necrosis factor-alpha
      (TNF-alpha) levels were up to 50% lower than in wt controls after 6 h. This
      reduced synthesis of proinflammatory cytokines occurred well before leucocyte
      recruitment to the central nervous system (CNS) is observed in this model of
      acute inflammation and thus cannot be attributed to lower numbers of recruited
      monocytes at the site of injury. We propose that MCP-1 contributes to acute CNS
      inflammation by pleiotropic mechanisms. In addition to being a potent
      chemoattractant for monocytes, we provide evidence here that MCP-1 can modify the
      responsiveness of CNS glia to acute inflammatory stimuli prior to leucocyte
      recruitment, thereby acting as a priming stimulus for cytokine synthesis in cells
      such as microglia.

PMID- 16882010
TI  - Regulation of the glutamate transporter EAAC1 by expression and activation of
      delta-opioid receptor.
AB  - Glutamate transporters play an essential role in regulating temporal and spatial
      glutamate concentration in the synaptic cleft. The excitatory amino acid carrier
      1 (EAAC1) is a neuronal-specific transporter. Opioid receptors are found to
      modulate the glutamatergic system in brain, but the regulatory mechanism remains
      to be investigated. Here we report that the delta-opioid receptor (DOR) co
      expressed with EAAC1 in Xenopus oocytes, but not the micro-opioid receptor, down
      regulates EAAC1 function, and that [d-Pen(2,5)]-enkephalin stimulation of DOR can
      counteract the down-regulation of the EAAC1-mediated uptake. Results from co
      immunoprecipitation and immunofluorescence microscopy in both oocytes and rat
      hippocampal neurons indicate co-localization and suggest direct interaction
      between DOR and EAAC1. The results suggest that DOR can reduce EAAC1 function by
      direct protein-protein interaction and that activation of DOR releases the
      inhibitory interaction. We suggest that this mechanism may be important for
      modulation of the glutamatergic system following opioid stimulation.

PMID- 16882012
TI  - Neurotensin afferents of the ventral tegmental area in the rat: [1] re
      examination of their origins and [2] responses to acute psychostimulant and
      antipsychotic drug administration.
AB  - The ventral tegmental area (VTA) is involved in reward-related behaviours and the
      actions of psychostimulant drugs. It is influenced by afferents expressing a
      variety of neurotransmitters and neuromodulators; the innervation containing
      neurotensin is among the densest of these. Intra-VTA neurotensin activates
      dopaminergic neurons and plays an important role in the development of
      behavioural sensitization to psychostimulant drugs and possibly in schizophrenia.
      Using gold-coupled wheatgerm agglutinin as retrograde tracer in combination with
      nonisotopic in situ hybridization for neurotensin mRNA or neurotensin antibodies
      after colchicine treatment, the present study was undertaken to demonstrate the
      neurotensinergic neurons projecting to the VTA and determine whether (and in
      which subpopulations) neurotensin expression is regulated in VTA-projecting
      neurons after administrations of the psychostimulant drug methamphetamine or the
      antipsychotic haloperidol. This study reveals the lateral preoptico-rostral
      lateral hypothalamic continuum and the medial preoptic area as main sources for
      the neurotensin afferents of the VTA. Fewer neurotensinergic, VTA-projecting
      neurons are situated in the dorsal raphe, pedunculopontine and laterodorsal
      tegmental nuclei, lateral hypothalamic area, ventral endopiriform area, lateral
      septum, accumbens shell, parabrachial nucleus and different parts of the extended
      amygdala. The number of neurotensinergic VTA-projecting neurons increased
      significantly only after methamphetamine administration and exclusively in the
      accumbens shell. It is concluded that the widespread neurotensinergic VTA
      projecting neurons, situated in areas involved in different reward-related
      behaviours, are well suited to convey distinct reward information to the VTA. The
      up-regulation of neurotensin expression selectively in VTA-projecting neurons in
      the accumbens shell following methamphetamine administration may be an important
      factor in the development of behavioural sensitization.

PMID- 16882013
TI  - The septal EEG suggests a distributed organization of the pacemaker of
      hippocampal theta in the rat.
AB  - Individual neurons in the medial septum and diagonal band fire in phase with, and
      appear to act as a 'pacemaker' of, the hippocampal theta rhythm. We investigated
      the relationships of periodic EEG both among various parts of the septum and with
      dorsal hippocampal theta recorded concurrently in freely moving rats. Most septal
      sites showed theta rhythm concurrent with hippocampal theta during locomotion.
      However, periods with theta at hippocampal but not septal sites were more
      frequent than the reverse. Theta waves in different parts of the septum were
      synchronized with each other but medial septal sites showed less frequent theta
      than other sites. The phase delays between medial and lateral septal sites were <
      10 ms, suggesting that the hippocampus does not act as a simple relay between the
      two. Spectral analysis revealed periods (> 5 s) of theta at hippocampal sites co
      occurring with rhythms at multiple septal sites that were slower than theta. Even
      slower were the 'slow septal waves' (mean 2.7 Hz), which were present in the
      absence of locomotion and did not 'drive' the hippocampus. Our data suggest that
      the pacemaker of hippocampal theta may best be thought of as a set of
      functionally differentiated components rather than as a single homogenous unit.

PMID- 16882011
TI  - Regulated expression of HCN channels and cAMP levels shape the properties of the
      h current in developing rat hippocampus.
AB  - The hyperpolarization-activated current (I(h)) contributes to intrinsic
      properties and network responses of neurons. Its biophysical properties depend on
      the expression profiles of the underlying hyperpolarization-activated, cyclic
      nucleotide-gated (HCN) channels and the presence of cyclic AMP (cAMP) that
      potently and differentially modulates I(h) conducted by HCN1, HCN2 and/or HCN4.
      Here, we studied the properties of I(h) in hippocampal CA1 pyramidal cells, the
      developmental evolution of the HCN-subunit isoforms that contribute to this
      current, and their interplay with age-dependent free cAMP concentrations, using
      electrophysiological, molecular and biochemical methods. I(h) amplitude increased
      progressively during the first four postnatal weeks, consistent with the observed
      overall increased expression of HCN channels. Activation kinetics of the current
      accelerated during this period, consonant with the quantitative reduction of mRNA
      and protein expression of the slow-kinetics HCN4 isoform and increased levels of
      HCN1. The sensitivity of I(h) to cAMP, and the contribution of the slow component
      to the overall I(h), decreased with age. These are likely a result of the
      developmentally regulated transition of the complement of HCN channel isoforms
      from cAMP sensitive to relatively cAMP insensitive. Thus, although hippocampal
      cAMP concentrations increased over twofold during the developmental period
      studied, the coordinated changes in expression of three HCN channel isoforms
      resulted in reduced effects of this signalling molecule on neuronal h currents.

PMID- 16882014
TI  - The role of GABAbeta2 subunit-containing receptors in mediating the
      anticonvulsant and sedative effects of loreclezole.
AB  - The majority of inhibitory neurotransmission in the brain is mediated by the
      gamma-aminobutyric acid (GABA) type A (GABA(A)) receptor. The anticonvulsant
      loreclezole largely acts by potentiating GABA(A) receptors containing beta2 and
      beta3 subunits. We used a genetically modified mouse containing a loreclezole
      insensitive beta2 subunit (beta2N265S) to determine the role of this subunit in
      mediating the sedative and anticonvulsive effects of loreclezole. Sedation was
      assessed by measuring spontaneous locomotor activity and beam walking
      performance, and anticonvulsant efficacy was determined by pentylenetetrazole
      (PTZ) and amygdala kindling-induced seizures. The beta2N265S mice did not exhibit
      loreclezole-mediated sedation as shown by normal locomotor activity and beam
      walking performance. However, loreclezole also failed to provide significant
      protection against PTZ-induced seizures in the beta2N265S mice. Reduced efficacy
      against amygdala-kindled seizures, both acutely and over a 13-day chronic dosing
      study, was also observed in beta2N265S mice. These results suggest that the
      majority of the sedative effects and a significant proportion of the
      anticonvulsant efficacy of loreclezole are mediated via beta2-containing GABA(A)
      receptors.

PMID- 16882015
TI  - Altered emotional behavioral responses in mice lacking brain-type fatty acid
      binding protein gene.
AB  - Brain-type fatty acid-binding protein (B-FABP) belongs to a family of
      intracellular lipid-binding proteins. B-FABP exhibits a binding affinity to long
      chain fatty acids (FAs) whose effects on brain functions including development,
      emotion, learning and memory have been proposed. B-FABP is localized in the
      ventricular germinal cells in embryonic brain and astrocytes in developing and
      mature brain of rodents. In the present study we generated the mouse harboring a
      null mutation in the B-FABP gene and studied its phenotype. B-FABP mutant mice
      exhibited the enhanced anxiety and increased fear memory as well as the decreased
      content of docosahexaenoic acid (DHA) in their brain during the neonatal period
      without detection of any histological changes in the brain. In the adult brain, B
      FABP was localized more numerously to the astrocytes in the amygdala and septal
      area than to those in the hippocampal area. Analysis of FA content in the
      amygdala of adult brain revealed that arachidonic and palmitic acids increased
      significantly in the mutant mice compared with wild-type. Furthermore, the
      response of N-methyl-d-aspartate receptor-mediated current to DHA in isolated
      neurons from B-FABP mutant brain was significantly decreased compared with that
      of wild-type, while no significant differences were detected in behavioral
      responses related to the spatial learning/memory or in the hippocampal long-term
      potentiation. These data indicate that B-FABP is crucially involved in the fear
      memory and anxiety through its binding with FAs and/or its own direct effects on
      pertinent metabolism/signaling of FAs.

PMID- 16882016
TI  - Neurotensin antagonist acutely and robustly attenuates locomotion that
      accompanies stimulation of a neurotensin-containing pathway from rostrobasal
      forebrain to the ventral tegmental area.
AB  - Neurotensin exerts complex effects on the mesolimbic dopamine system that alter
      motivation and contribute to neuroadaptations associated with psychostimulant
      drug administration. Activation of abundant neurotensin receptors in the ventral
      tegmental area (VTA) enhances dopamine neuron activity and associated release of
      dopamine in the nucleus accumbens (Acb) and cortex. In view of recent anatomical
      studies demonstrating that 70% of all neurotensin-containing neurons projecting
      to the VTA occupy the lateral preoptic area-rostral lateral hypothalamus (LPH)
      and lateral part of the medial preoptic area (MPOA), the present study examined
      functionality in the LPH-MPOA neurotensinergic pathway in the rat. Disinhibition
      (resulting ultimately in stimulation-like effects) of LPH-MPOA neurons with
      microinjected bicuculline (50 or 100 ng in 0.25 microL) produced locomotor
      activation that was considerably attenuated by systemic administration of the
      neurotensin antagonist SR 142948 A (0.03 and 0.1 mg/kg). In contrast, locomotion
      elicited in this manner was completely blocked by SR 142948 A infused directly
      into the VTA (5.0 and 15.0 ng in 0.25 microL). Baseline locomotion was unaffected
      by systemic or intra-VTA administration of SR 142948 A and LPH-MPOA-elicited
      locomotion was unaffected by infusion of SR 142948 A into the substantia nigra
      pars compacta and sites rostral and dorsal to the VTA. Locomotion was not
      elicited by infusions of bicuculline into the lateral hypothalamus at sites
      caudal to the LPH-MPOA, where neurotensin neurons projecting to the VTA are
      fewer. The results demonstrate the capacity of a neurotensin-containing pathway
      from LPH-MPOA to VTA to modulate locomotion. This pathway may be important in
      linking hippocampal and mesolimbic mechanisms in normal behaviour and drug
      addiction.

PMID- 16882017
TI  - Repeated withdrawal from ethanol spares contextual fear conditioning and spatial
      learning but impairs negative patterning and induces over-responding: evidence
      for effect on frontal cortical but not hippocampal function?
AB  - Repeated exposure of rats to withdrawal from chronic ethanol reduces hippocampal
      long-term potentiation and gives rise to epileptiform-like activity in
      hippocampus. We investigated whether such withdrawal experience also affects
      learning in tasks thought to be sensitive to hippocampal damage. Rats fed an
      ethanol-containing diet for 24 days with two intermediate 3-day withdrawal
      episodes, resulting in intakes of 13-14 g/kg ethanol per day, showed impaired
      negative patterning discrimination compared with controls and animals that had
      continuous 24-day ethanol treatment, but did not differ from these animals in the
      degree of contextual freezing 24 h after training or in spatial learning in the
      Barnes maze. Repeatedly withdrawn animals also showed increased numbers of
      responses in the period immediately before reinforcement became available in an
      operant task employing a fixed-interval schedule although overall temporal
      organization of responding was unimpaired. Thus, in our model of repeated
      withdrawal from ethanol, previously observed changes in hippocampal function did
      not manifest at the behavioural level in the tests employed. The deficit seen
      after repeated withdrawal in the negative patterning discrimination and over
      responding in the fixed-interval paradigm might be related to the changes in the
      functioning of the cortex after withdrawal.

PMID- 16882018
TI  - Context-dependent behavioural and neuronal sensitization in striatum to MDMA
      (ecstasy) administration in rats.
AB  - To investigate the neuronal mechanisms underlying the behavioural alterations
      that accompany repeated exposure to MDMA (ecstasy), we recorded the activity of >
      200 striatal units in response to multiple, intermittent, locomotor-activating
      doses (5.0 mg/kg) of MDMA. Rats were treated with once-daily injections of either
      saline or MDMA for 5 days when housed in their home cage, followed by a challenge
      injection 3-5 days later when housed in a recording chamber. Because contextual
      drug associations might be particularly important to the expression of
      behavioural sensitization to chronic MDMA, a separate group of rats received
      repeated injections of MDMA alternately in the recording chamber or home cage,
      according to the above timeline. A sensitized locomotor response was observed
      only in rats that had previously experienced MDMA in the context of the recording
      chamber, and only on the challenge day. These sensitized animals also showed a
      decreased basal firing rate in neurons that were subsequently excited by MDMA
      when compared with the same category of neurons earlier in the treatment regimen.
      This resulted in a greater percentage increase from the baseline firing rate on
      the challenge day compared with the first and fifth days of treatment, even
      though this trend was not evident with an analysis of absolute firing rate. These
      results strongly support a role for context in the expression of MDMA-induced
      locomotor sensitization, and implicate striatal involvement in the
      neurobehavioural changes associated with the repeated use of MDMA.

PMID- 16882019
TI  - Progesterone reverses the spatial memory enhancements initiated by tonic and
      cyclic oestrogen therapy in middle-aged ovariectomized female rats.
AB  - While some research has indicated that ovarian hormone therapy (HT) benefits
      memory and decreases risk of Alzheimer's disease in menopausal women, several
      newer studies have shown null or detrimental effects. Despite the null and
      negative cognitive findings, the numerous studies showing positive effects beg
      the question of what factors determine whether HT acts as a neuroprotectant or a
      risk factor for brain functioning. Using middle-aged female rats, we directly
      compared six HTs. We evaluated the effects of ovariectomy, tonic low-dose, tonic
      high-dose and biweekly cyclic estradiol treatment, as well as whether
      progesterone altered the effectiveness of any one of these oestrogen regimens.
      Animals were tested on spatial and complex cued (intramaze patterns) reference
      memory using variants of the Morris maze. The tonic low-dose and cyclic estradiol
      treatments improved spatial performance, while the addition of progesterone
      reversed these beneficial cognitive effects of estradiol. Additionally, all
      groups learned to locate the platform on the cued task; however, an egocentric
      circling strategy was used with sham ovary-intact and hormone-replacement groups
      showing the most efficient search strategy. Although the question of memory
      retention 8 weeks after the first cognitive assessment was addressed, a large
      number of animals died between the first and second test, rendering the retest
      uninterpretable for many group comparisons. Specifically, both doses of tonic
      estradiol dramatically increased the number of deaths during the 17-week
      experiment, while the cyclic estradiol treatment did not. Progesterone decreased
      the number of deaths due to tonic estradiol treatment. Our findings suggest that
      the dose of estradiol replacement as well as the presence of progesterone
      influences the cognitive outcome of estradiol treatment. Further, there appears
      to be a dissociation between HT effects on cognition and mortality rates.

PMID- 16882020
TI  - Selective rapid eye movement sleep deprivation impairs the maintenance of long
      term potentiation in the rat hippocampus.
AB  - Rapid eye movement (REM) sleep deprivation (RSD) is known to impair learning and
      memory. Previous studies have demonstrated that RSD induces an impairment of
      hippocampal long-term potentiation (LTP). In most of these studies, RSD was set
      up prior to LTP induction. In this work, we focused on RSD after LTP induction.
      We investigated the effect of RSD for 24-48 h after induction of LTP in the
      dentate gyrus on LTP maintenance and whether a REM rebound after 48 h RSD
      affected LTP. RSD rats were deprived of REM sleep by stroking their backs using a
      brush, whereas control rats were allowed to sleep freely. Another control group
      of rats was awoken during non-REM sleep (NRS) under the same conditions (NRS
      group). REM-deprived rats displayed a faster decay of population spike amplitudes
      compared with the control and NRS groups over a 24-h recording time. After 48 h
      RSD, there was no difference in the population spike amplitudes before or after 4
      h of release from RSD. These results suggest that REM sleep after LTP induction
      in the dentate gyrus plays an essential role in LTP maintenance, whereas a REM
      rebound does not restore the RSD-induced impairment of LTP.

PMID- 16882021
TI  - Extinction is not a sufficient condition to prevent fear memories from undergoing
      reconsolidation in the basolateral amygdala.
AB  - Consolidated memories when reactivated may return to a state that requires
      protein synthesis in order to be restabilized (reconsolidation). It has been
      shown in a variety of systems that if reactivation induces significant extinction
      then extinction is the protein synthesis dependent memory state, rather than
      reconsolidation. Thus, extinction consolidation may prevent the memory from
      undergoing reconsolidation. We investigated whether such an interaction also
      exists between extinction and reconsolidation of fear memories within the
      amygdala, by using a within subjects experimental design. We found that
      inhibition of protein synthesis in the basolateral amygdala (BLA) impaired
      reconsolidation for both the briefly reactivated and extinguished fear memories
      suggesting that extinction is not a sufficient condition to prevent induction of
      reconsolidation in the amygdala. These findings demonstrate that extinction
      consolidation does not always interact with reconsolidation. Therefore, under
      these conditions, extinction is not a boundary condition on reconsolidation of
      fear memories in the basolateral amygdala.

PMID- 16882022
TI  - Extinction of auditory fear conditioning requires MAPK/ERK activation in the
      basolateral amygdala.
AB  - Whereas the neuronal substrates underlying the acquisition of auditory fear
      conditioning have been widely studied, the substrates and mechanisms mediating
      the acquisition of fear extinction remain largely elusive. Previous reports
      indicate that consolidation of fear extinction depends on the mitogen-activated
      protein kinase/extracellular-signal regulated kinase (MAPK/ERK) signalling
      pathway and on protein synthesis in the medial prefrontal cortex (mPFC). Based on
      experiments using the fear-potentiated startle paradigm suggesting a role for
      neuronal plasticity in the basolateral amygdala (BLA) during fear extinction, we
      directly addressed whether MAPK/ERK signalling in the basolateral amygdala is
      necessary for the acquisition of fear extinction using conditioned freezing as a
      read-out. First, we investigated the regional and temporal pattern of MAPK/ERK
      activation in the BLA following extinction learning in C57Bl/6J mice. Our results
      indicate that acquisition of extinction is associated with an increase of
      phosphorylated MAPK/ERK in the BLA. Moreover, we found that inhibition of the
      MAPK/ERK signalling pathway by intrabasolateral amygdala infusion of the MEK
      inhibitor, U0126, completely blocks acquisition of extinction. Thus, our results
      indicate that the MAPK/ERK signalling pathway is required for extinction of
      auditory fear conditioning in the BLA, and support a role for neuronal plasticity
      in the BLA during the acquisition of fear extinction.

PMID- 16882023
TI  - Substantia nigra pars compacta is critical to both the acquisition and expression
      of learned orienting of rats.
AB  - Novel events produce characteristic orienting responses (ORs), which typically
      habituate rapidly with repeated stimulus presentation. However, they may re
      emerge if those stimuli become predictors of biologically significant events.
      This acquisition of conditioned ORs may reflect a broader range of enhancements
      in top-down attentional processing of cues that predict important consequences.
      Previous research from this laboratory showed that a neural circuit that includes
      the amygdala central nucleus (CeA), substantia nigra pars compacta (SNc) and
      dorsolateral striatum (DLS) is essential for the learning and expression of one
      example of conditioned orienting, the rearing of rats to visual stimuli paired
      with food. Other studies showed that the CeA is critical to the acquisition of
      these conditioned ORs, but not their expression, and that normal DLS function is
      required for the expression of previously acquired conditioned ORs, but not for
      learning itself. The experiments reported here considered the roles of the SNc in
      conditioned orienting by examining the effects of transient inactivation of the
      SNc during the acquisition of new associations and during the expression of
      previous learning. SNc function was critical to both the acquisition and
      expression of conditioned ORs but not to the display of unconditioned ORs or the
      learning and expression of conditioned responses directed to the food source.
      Together with our previous findings, these results suggest that the SNc is
      trained by the CeA during learning and maintains acquired information so that it
      may modulate DLS sensory-motor function at the time of action.

PMID- 16882024
TI  - Dopamine neuronal responses in monkeys performing visually cued reward schedules.
AB  - Dopamine neurons are important for reward-related behaviours. They have been
      recorded during classical conditioning and operant tasks with stochastic reward
      delivery. However, daily behaviour, although frequently complex in the number of
      steps, is often very predictable. We studied the responses of 75 dopamine neurons
      during schedules of trials in which the events and related reward contingencies
      could be well-predicted, within and across trials. In this visually cued reward
      schedule task, a visual cue tells the monkeys exactly how many trials, 1, 2, 3,
      or 4, must be performed to obtain a reward. The number of errors became larger as
      the number of trials remaining before the reward increased. Dopamine neurons
      frequently responded to the cues at the beginning and end of the schedules.
      Approximately 75% of the first-cue responsive neurons did not distinguish among
      the schedules that were beginning even though the cues were different.
      Approximately half of the last-cue responsive neurons depended on which schedule
      was ending, even though the cue signalling the last trial was the same in all
      schedules. Thus, the responses were related to what the monkey knew about the
      relation between the cues and the schedules, not the identity of the cues. These
      neurons also frequently responded to the go signal and/or to the OK signal
      indicating the end of a correctly performed trial whether a reward was
      forthcoming or not, and to the reward itself. Thus, dopamine neurons seem to
      respond to behaviourally important, i.e. salient, events even when the events
      have been well-predicted.

PMID- 16882025
TI  - Dynamics of narrow-band EEG phase effects in the passive auditory oddball task.
AB  - Evidence suggests that the component frequencies of the electroencephalogram
      (EEG) are dynamically adjusted to provide particular brain states at stimulus
      occurrence, and that these facilitate cortical processing of the stimulus. We
      examined relationships between stimulus intensity, the phase of narrow-band EEG
      activity at stimulus onset, and the resultant event-related potentials (ERPs) in
      a passive auditory oddball task, using a novel conceptualization of orthogonal
      phase effects (cortical negativity vs. positivity, negative driving vs. positive
      driving, waxing vs. waning). EEG responses to the standard stimuli (50 vs. 80 dB,
      varied between subjects) were analysed. Prestimulus narrow-band EEG activity (in
      1-Hz bands from 1 to 13 Hz) at Cz was assessed for each trial by digital
      filtering. For each frequency, the cycle at stimulus onset was used to sort
      trials into four phases, for which ERPs were derived from both the filtered and
      unfiltered EEG activity at Fz, Cz and Pz. Preferred brain states at various
      frequencies were indicated by 16-34% differential occurrence within the
      orthogonal phase dimensions explored. The preferred states were associated with
      smaller N1, N2 and N3, larger P2 and P3, shorter N1, P2, N2 and P3 latencies, and
      some intensity effects. These effects reflected the operation of three separate
      phase-influenced mechanisms, involving anticipatory potentials and
      prestimulus/poststimulus amplitudes in various EEG frequencies. Results indicate
      that, even in paradigms with a slightly varying interstimulus interval, brain
      dynamics provide preferred brain states at the moment of stimulus presentation,
      which differentially affect the EEG correlates of stimulus processing.

PMID- 16882026
TI  - Net influx of plasma 6-[18F]fluoro-L-DOPA (FDOPA) to the ventral striatum
      correlates with prefrontal processing of affective stimuli.
AB  - Dopaminergic neurotransmission in the ventral and dorsal striatum interact with
      central processing of rewarding and reward-indicating stimuli, and may affect
      frontocortical-striatal-thalamic circuits regulating goal-directed behaviour.
      Thirteen healthy male volunteers were investigated with multimodal imaging, using
      the radioligand 6-[(18)F]fluoro-l-DOPA (FDOPA) for positron emission tomography
      (PET) measurements of dopamine synthesis capacity, and also functional magnetic
      resonance imaging (fMRI) in a cognitive activation paradigm. We calculated the
      correlation between FDOPA net blood-brain influx (; ml/g/min) in the ventral and
      associative dorsal striatum and BOLD signal changes elicited by standardized
      affectively positive, negative and neutral visual stimuli. The magnitude of in
      the ventral striatum was positively correlated with BOLD signal increases in the
      left anterior cingulate cortex and right insular operculum elicited by positive
      vs. neutral stimuli, but not negative vs. neutral stimuli. In the dorsal
      striatum, the magnitude of was positively correlated with processing of positive
      and negative stimuli in the left dorsolateral prefrontal cortex. These findings
      suggest that dopamine synthesis capacity in the ventral striatum correlates with
      the attentional processing of rewarding positive stimuli in the anterior
      cingulate cortex of healthy subjects. Dopaminergic neurotransmission in the
      associative dorsal striatum has been associated previously with habit learning.
      The observed correlation between dopamine synthesis capacity in the dorsal
      striatum and BOLD signal changes in the dorsolateral prefrontal cortex suggests
      dopaminergic modulation of processing of emotional stimuli in brain areas
      associated with motor planning and executive behaviour control.

PMID- 16882028
TI  - Virulence strategies for infecting phagocytes deduced from the in vivo
      transcriptional program of Legionella pneumophila.
AB  - Adaptation to the host environment and exploitation of host cell functions are
      critical to the success of intracellular pathogens. Here, insight to these
      virulence mechanisms was obtained for the first time from the transcriptional
      program of the human pathogen Legionella pneumophila during infection of its
      natural host, Acanthamoeba castellanii. The biphasic life cycle of L. pneumophila
      was reflected by a major shift in gene expression from replicative to
      transmissive phase, concerning nearly half of the genes predicted in the genome.
      However, three different L. pneumophila strains showed similar in vivo gene
      expression patterns, indicating that common regulatory mechanisms govern the
      Legionella life cycle, despite the plasticity of its genome. During the
      replicative phase, in addition to components of aerobic metabolism and amino acid
      catabolism, the Entner-Doudoroff pathway, a NADPH producing mechanism used for
      sugar and/or gluconate assimilation, was expressed, suggesting for the first time
      that intracellular L. pneumophila may also scavenge host carbohydrates as
      nutrients and not only proteins. Identification of genes only upregulated in vivo
      but not in vitro, may explain higher virulence of in vivo grown L. pneumophila.
      Late in the life cycle, L. pneumophila upregulates genes predicted to promote
      transmission and manipulation of a new host cell, therewith priming it for the
      next attack. These including substrates of the Dot/Icm secretion system, other
      factors associated previously with invasion and virulence, the motility and the
      type IV pilus machineries, and > 90 proteins not characterized so far. Analysis
      of a fliA (sigma28) deletion mutant identified genes coregulated with the
      flagellar regulon, including GGDEF/EAL regulators and factors that promote host
      cell entry and survival.

PMID- 16882030
TI  - Neisseria gonorrhoeae PLD directly interacts with Akt kinase upon infection of
      primary, human, cervical epithelial cells.
AB  - Neisseria gonorrhoeae secrets a phospholipase D (NgPLD), which augments
      complement receptor 3 (CR3)-mediated invasion of cervical epithelial cells. To
      elucidate the signalling pathways triggered with gonococcus CR3-engagement and
      the putative function of NgPLD in these events, we analysed the contribution of
      the phosphoinositide-Akt pathway to cervical infection. Our data indicated that
      Akt plays a critical role in cervical infection. Inhibition of myosin light chain
      kinase, PtdIns(4,5)P2, and Akt functions resulted in decreased gonococcus
      invasion of primary, human, cervical epithelial cells as well as Akt kinase
      activity. Akt activity was similarly impaired when cervical cells were challenged
      with NgPLD-mutant gonococci. Conversely, the PI3-kinase inhibitor, LY294002,
      enhanced gonococcal invasion of, and Akt activity within, primary cervical cells.
      We demonstrated that NgPLD directly binds to the Akt PH domain and can compete
      with a natural Akt ligand, PtdIns(3,4,5)P3, for Akt binding. Collectively, our
      data suggested that NgPLD augments gonococcus invasion of cervical epithelia by
      interacting with Akt kinase in a PI3-kinase-independent manner, which results in
      subversion of normal cervical cell signalling.

PMID- 16882027
TI  - Cholinergic modulation of response properties and orientation tuning of neurons
      in primary visual cortex of anaesthetized Marmoset monkeys.
AB  - Cortical processing is strongly influenced by the actions of neuromodulators such
      as acetylcholine (ACh). Early studies in anaesthetized cats argued that
      acetylcholine can cause a sharpening of orientation tuning functions and an
      improvement of the signal-to-noise ratio (SNR) of neuronal responses in primary
      visual cortex (V1). Recent in vitro studies have demonstrated that acetylcholine
      reduces the efficacy of feedback and intracortical connections via the activation
      of muscarinic receptors, and increases the efficacy of feed-forward connections
      via the activation of nicotinic receptors. If orientation tuning is mediated or
      enhanced by intracortical connections, high levels of acetylcholine should
      diminish orientation tuning. Here we investigate the effects of acetylcholine on
      orientation tuning and neuronal responsiveness in anaesthetized marmoset monkeys.
      We found that acetylcholine caused a broadening of the orientation tuning in the
      majority of cells, while tuning functions became sharper in only a minority of
      cells. Moreover, acetylcholine generally facilitated neuronal responses, but
      neither improved signal-to-noise ratio, nor reduced trial-to-trial firing rate
      variance systematically. Acetylcholine did however, reduce variability of spike
      occurrences within spike trains. We discuss these findings in the context of
      dynamic control of feed-forward and lateral/feedback connectivity by
      acetylcholine.

PMID- 16882029
TI  - Intra-leukocyte expression of two-component systems in Ehrlichia chaffeensis and
      Anaplasma phagocytophilum and effects of the histidine kinase inhibitor
      closantel.
AB  - The two-component system (TCS) composed of a pair of a sensor histidine kinase
      and a response regulator, allows bacteria to sense signals and respond to changes
      in their environment through specific gene activation or repression. The present
      study examined TCS in the obligatory intracellular bacteria Ehrlichia chaffeensis
      and Anaplasma phagocytophilum, that cause human monocytic ehrlichiosis (HME) and
      human granulocytic anaplasmosis (HGA) respectively. The genomes of E. chaffeensis
      and A. phagocytophilum were each predicted to encode three pairs of TCSs. All six
      genes encoding three histidine kinases and three response regulators were
      expressed in both E. chaffeensis and A. phagocytophilum cultured in human
      leukocytes. Pretreatment of host cell-free E. chaffeensis or A. phagocytophilum
      with closantel, an inhibitor of histidine kinases, completely blocked the
      infection of host cells. Treatment of infected cells 1 day post infection with
      closantel cleared infection in dose-dependent manner. All six genes in E.
      chaffeensis were cloned, recombinant proteins were expressed, and polyclonal
      antibodies were produced. Double immunofluorescence labelling and Western blot
      analysis revealed that all six proteins were expressed in cell culture.
      Autokinase activities of the three recombinant histidine kinases from E.
      chaffeensis were inhibited by closantel in vitro. A number of E. chaffeensis
      genes, including the six TCS genes, were downregulated within 5-60 min post
      closantel treatment. These results suggest that these TCSs play an essential role
      in infection and survival of E. chaffeensis and A. phagocytophilum in human
      leukocytes.

PMID- 16882032
TI  - Early expression of SCIN and CHIPS drives instant immune evasion by
      Staphylococcus aureus.
AB  - Chemotaxis inhibitory protein of staphylococci (CHIPS) and Staphylococcal
      complement inhibitor (SCIN) are small, excreted molecules that play a crucial
      role in the staphylococcal defence against the human innate immune system. Here
      we show that they both counteract crucial acute responses of our immune system
      such as complement activation, neutrophil chemotaxis and neutrophil activation.
      By studying gene expression via promoter-green fluorescent protein fusions,
      Northern blots and protein expression analyses, we show that SCIN and CHIPS are
      produced during the early (exponential) growth stages. Although the SCIN and
      CHIPS genes are expressed simultaneously, they are differently regulated by
      various Staphylococcus aureus regulatory loci. However, the sae locus is crucial
      for upregulation of both SCIN and CHIPS. This is the first study that presents
      the expression of two extracellular S. aureus proteins early during growth.
      Because SCIN and CHIPS are both efficient modulators of neutrophil chemotaxis,
      phagocytosis and killing, their early expression is necessary for efficient
      modulation of the early immune response.

PMID- 16882031
TI  - Cytotoxic activity of Bacillus anthracis protective antigen observed in a
      macrophage cell line overexpressing ANTXR1.
AB  - Anthrax toxin protective antigen (PA) binds cell surface receptors (e.g.
      ANTXR1,2), forms heptameric pores, and translocates lethal factor (LF) or oedema
      factor (OF) into the cytoplasm of mammalian cells. In the current study, we
      sought to determine how receptor levels influence these events, by examining PA
      heptamer stability and related processes in macrophages that overexpress ANTXR1
      (RAW 264.7ANTXR1). In these experiments, PA-oligomers demonstrated an extended
      half-life in RAW 264.7ANTXR1 macrophages, with SDS-resistant heptamers detected
      up to 10 h following treatment, while levels of PA-oligomers declined within 3 h
      in control cells. RAW 264.7ANTXR1 macrophages were also more sensitive to lethal
      toxin, a combination of PA and LF. Surprisingly, we found that PA alone was
      cytotoxic to RAW 264.7ANTXR1 cells. Further analysis found that PA cytotoxicity
      required direct interaction with ANTXR1, oligomerization, channel formation,
      endosomal acidification, and was independent of the ANTXR1 cytoplasmic tail. PA
      intoxication of RAW 264.7ANTXR1 macrophages resulted in caspase-3 activation,
      with corresponding DNA fragmentation and proteolytic cleavage of poly-ADP-ribose
      polymerase, as well as activation of Bid, suggesting cell death occurred via
      apoptosis. Overall, results from the current study suggest that receptor levels
      dictate the extent of PA oligomer stability, and shifts in this normal process
      can lead to cell death via apoptosis in the absence of toxin catalytic subunits.

PMID- 16882034
TI  - Botrytis cinerea virulence is drastically reduced after disruption of chitin
      synthase class III gene (Bcchs3a).
AB  - Botrytis cinerea is an important phytopathogenic fungus requiring new methods of
      control. Chitin biosynthesis, which involves seven classes of chitin synthases,
      could be an attractive target. A fragment encoding one of the class III enzymes
      was used to disrupt the corresponding Bcchs3a gene in the B. cinerea genome. The
      resulting mutant exhibited a 39% reduction in its chitin content and an 89%
      reduction in its in vitro chitin synthase activity, compared with the wild-type
      strain. Bcchs3a mutant was not affected in its growth in liquid medium, neither
      in its production of sclerotia, micro- and macroconidia. In contrast, the mutant
      Bcchs3a was severely impaired in its growth on solid medium. Counterbalancing
      this defect in radial growth, Bcchs3a mutant presented a large increase in hyphal
      ramification, resulting in an enhanced aerial growth. Observations by different
      techniques of microscopy revealed a thick extracellular matrix around the hyphal
      tips. Moreover, Bcchs3a mutant had a largely reduced virulence on Vitis vinifera
      and Arabidopsis thaliana leaves.

PMID- 16882033
TI  - Eukaryotic localization, activation and ubiquitinylation of a bacterial type III
      secreted toxin.
AB  - Type III secretion is a widespread method whereby Gram-negative bacteria
      introduce toxins into eukaryotic cells. These toxins mimic or subvert a normal
      cellular process by interacting with a specific target, although how toxins reach
      their site of action is unclear. We set out to investigate the intracellular
      localization of a type III toxin of Pseudomonas aeruginosa called ExoU, which has
      phospholipase activity and requires a eukaryotic factor for activity. We found
      that ExoU is localized to the plasma membrane and undergoes modification within
      the cell by addition of two ubiquitin molecules at lysine-178. A region of five
      amino acids at position 679-683 near the C-terminus of the ExoU protein controls
      both membrane localization and ubiquitinylation. Site-directed mutagenesis
      identified a tryptophan at position 681 as crucial for these effects. We found
      that the same region at position 679-683 was also required for cell toxicity
      produced by ExoU as well as in vitro phospholipase activity. Localization of the
      phospholipase ExoU to the plasma membrane is thus required for activation and
      allows efficient utilization of adjacent substrate phospholipids.

PMID- 16882035
TI  - Synthesis of phosphatidylcholine, a typical eukaryotic phospholipid, is necessary
      for full virulence of the intracellular bacterial parasite Brucella abortus.
AB  - Phosphatidylcholine (PC) is a typical eukaryotic phospholipid absent from most
      prokaryotes. Thus, its presence in some intracellular bacteria is intriguing as
      it may constitute host mimicry. The role of PC in Brucella abortus was examined
      by generating mutants in pcs (BApcs) and pmtA (BApmtA), which encode key enzymes
      of the two bacterial PC biosynthetic routes, the choline and methyl-transferase
      pathways. In rich medium, BApcs and the double mutant BApcspmtA but not BApmtA
      displayed reduced growth, increased phosphatidylethanolamine and no PC, showing
      that Pcs is essential for PC synthesis under these conditions. In minimal medium,
      the parental strain, BApcs and BApmtA showed reduced but significant amounts of
      PC suggesting that PmtA may also be functional. Probing with phage Tb,
      antibiotics, polycations and serum demonstrated that all mutants had altered
      envelopes. In macrophages, BApcs and BApcspmtA showed reduced ability to evade
      fusion with lysosomes and establish a replication niche. In mice, BApcs showed
      attenuation only at early times after infection, BApmtA at later stages and
      BApcspmtA throughout. The results suggest that Pcs and PmtA have complementary
      roles in vivo related to nutrient availability and that PC and the membrane
      properties that depend on this typical eukaryotic phospholipid are essential for
      Brucella virulence.

PMID- 16882036
TI  - Bivalent role of the phosphatidylinositol-3-kinase (PI3K) during influenza virus
      infection and host cell defence.
AB  - Infections with influenza A viruses result in the activation of a variety of
      intracellular signalling pathways. Recent findings suggest that in response to
      double-stranded RNA (dsRNA), which is commonly used as a mimic for accumulating
      viral RNA, the phosphatidylinositol-3-kinase (PI3K) is activated and mediates
      activation of the transcription factor interferon regulatory factor 3 (IRF-3).
      Thus, we investigated the function of PI3K during influenza virus infection. The
      pathway was activated upon infection and consistent with earlier findings using
      dsRNA, inhibition of PI3K itself or block of signalling by the PI3K product, the
      second messenger phosphatidylinositol-3,4,5-trisphosphate (PIP3), results in
      misphosphorylation and impaired dimerization of IRF-3 as well as reduced IRF-3
      dependent promoter activity. This would imply an antiviral function of the kinase
      in influenza virus-infected cells. However, upon inhibition of PI3K, titers of
      progeny virus were reduced rather than enhanced. This was coincident with a
      strong decrease of viral protein accumulation that was not due to a block of
      protein synthesis or inhibition of the viral polymerase complex.
      Immunofluorescence studies revealed that PI3K rather appears to regulate a very
      early step during viral entry. Thus PI3K is a perfect example of a seemingly
      antiviral signalling component that is misused by the virus to support effective
      replication.

PMID- 16882037
TI  - Reciprocal upregulation of urokinase plasminogen activator and its inhibitor, PAI
      2, by Borrelia burgdorferi affects bacterial penetration and host-inflammatory
      response.
AB  - The mammalian plasminogen activation system (PAS) is a complex system involved in
      multiple physiological and pathological processes. Borrelia burgdorferi interacts
      with certain components of the PAS. Here we further investigate this interaction
      to determine its effect on bacterial dissemination and host cell migration in
      vitro. We show that stimulation of monocytic cells with B. burgdorferi induces
      the transient production and secretion of urokinase plasminogen activator (uPA),
      shortly followed by its physiological inhibitor, plasminogen activator inhibitor
      2 (PAI-2). Mono Mac 6 (MM6) cells as well as peripheral blood monocytes enhanced
      transmigration of B. burgdorferi across a barrier coated with fibronectin
      mediated by uPA. Moreover, the induction of PAI-2 or the addition of recombinant
      PAI-2 did not have a significant effect on the uPA-potentiated transmigration of
      B. burgdorferi. In contrast, the induction of PAI-2 by B. burgdorferi resulted in
      significantly diminished invasion by monocytic cells across a reconstituted
      basement membrane (matrigel), which could be partially restored by treatment with
      purified uPA. These results show that the PAS plays a twofold role in the
      pathogenesis of B. burgdorferi infection, both by enhancing bacterial
      dissemination and by diminishing host-cell inflammatory migration.

PMID- 16882038
TI  - Uptake of serum-opsonized Francisella tularensis by macrophages can be mediated
      by class A scavenger receptors.
AB  - The bacterium Francisella tularensis is highly infective, and this is one of the
      chief attributes that has led to its development as a bioweapon. Establishment of
      infection requires efficient uptake of F. tularensis by host macrophages, which
      provide a safe in vivo environment for F. tularensis replication. Little is
      known, however, about the cellular entry mechanisms employed by this organism.
      This report shows that efficient uptake of F. tularensis live vaccine strain
      (LVS) by macrophages is dependent on a heat-sensitive serum component and is
      mediated in part by types I and II class A scavenger receptors (SRA),
      demonstrating for the first time that SRA can act as a receptor for opsonized
      pathogens. Specifically, uptake of serum-opsonized LVS was partially blocked by
      general scavenger receptor inhibitors [fucoidan and poly(I)] and was largely
      inhibited by a specific function-blocking antibody against SRA. A role for SRA in
      LVS binding was confirmed by showing that ectopic expression of SRA in human
      embryonic kidney cells conferred the capacity for robust serum-dependent LVS
      binding. Finally, SRA-/- macrophages ingested significantly fewer LVS than did
      macrophages from wild-type mice. These findings support a novel role for SRA in
      innate immunity and suggest a potential therapeutic approach for modulating F.
      tularensis infection, namely, blocking SRA as a means of hindering F. tularensis
      access to its intracellular niche.

PMID- 16882039
TI  - Chlamydia trachomatis causes centrosomal defects resulting in chromosomal
      segregation abnormalities.
AB  - Chlamydiae traffic along microtubules to the microtubule organizing center (MTOC)
      to establish an intracellular niche within the host cell. Trafficking to the MTOC
      is dynein dependent although the activating and cargo-linking function of the
      dynactin complex is supplanted by unknown chlamydial protein(s). We demonstrate
      that once localized to the MTOC, the chlamydial inclusion maintains a tight
      association with cellular centrosomes. This association is sustained through
      mitosis and leads to a significant increase in supernumerary centrosomes,
      abnormal spindle poles, and chromosomal segregation defects. Chlamydial infection
      thus can lead to chromosome instability in cells that recover from infection.

PMID- 16882041
TI  - A mutation in Epstein-Barr virus LMP2A reveals a role for phospholipase D in B
      Cell antigen receptor trafficking.
AB  - Epstein-Barr virus (EBV) latent infection of B cells blocks the interrelated
      signaling and antigen-trafficking functions of the BCR through the activity of
      its latent membrane protein 2A (LMP2A). At present, the molecular mechanisms by
      which LMP2A exerts its control of BCR functions are only poorly understood.
      Earlier studies showed that in B cells expressing LMP2A containing a tyrosine
      mutation at position 112 in its cytoplasmic domain (Y112-LMP2A), the BCR could
      initiate signaling but could not properly traffic antigen for processing. Here,
      we show that BCR signaling in Y112-LMP2A-expressing cells is attenuated with a
      reduction in both the degree and duration of phosphorylation of key components of
      the BCR signaling cascade including Syk, BLNK, PI3K, and Btk. Notably, Y112-LMP2A
      expression completely blocked the BCR-induced activation of phospholipase D
      (PLD), a lipase implicated in the intracellular trafficking of a variety of
      surface receptors. We show that blocking PLD activity, by expressing Y112-LMP2A,
      treating cells with the PLD inhibitor 1-butanol or reducing PLD expression by
      siRNA, blocked BCR trafficking to class II-containing compartments. Moreover,
      Y112-LMP2A expression blocked the recruitment of phosphorylated forms of the
      downstream BCR signaling components, Erk and JNK, through both PLD-dependent and
      PLD-independent mechanisms. Thus, the investigation of the mechanism by which
      Y112-LMP2A blocks BCR function revealed an essential role for PLD in BCR
      trafficking for antigen processing.

PMID- 16882042
TI  - Extracting sequence motifs and the phylogenetic features of SNARE-dependent
      membrane traffic.
AB  - The SNARE proteins are required for membrane fusion during intracellular
      vesicular transport and for its specificity. Only the unique combination of SNARE
      proteins (cognates) can be bound and can lead to membrane fusion, although the
      characteristics of the possible specificity of the binding combinations encoded
      in the SNARE sequences have not yet been determined. We discovered by whole
      genome sequence analysis that sequence motifs (conserved sequences) in the SNARE
      motif domains for each protein group correspond to localization sites or
      transport pathways. We claim that these motifs reflect the specificity of the
      binding combinations of SNARE motif domains. Using these motifs, we could
      classify SNARE proteins from 48 organisms into their localization sites or
      transport pathways. The classification result shows that more than 10 SNARE
      subgroups are kingdom specific and that the SNARE paralogs involved in the plasma
      membrane-related transport pathways have developed greater variations in higher
      animals and higher plants than those involved in the endoplasmic reticulum
      related transport pathways throughout eukaryotic evolution.

PMID- 16882043
TI  - Robotics in urologic surgery: an evolving new technology.
AB  - Rapid technological developments in the past two decades have produced new
      inventions such as robots and incorporated them into our daily lives. Today,
      robots perform vital functions in homes, outer space, hospitals and on military
      instillations. The development of robotic surgery has given hospitals and health
      care providers a valuable tool that is making a profound impact on highly
      technical surgical procedures. The field of urology is one area of medicine that
      has adopted and incorporated robotic surgery into its armamentarium. Innovative
      robotic urologic surgical applications and techniques are being developed and
      reported everyday. Increased utilization and development will ultimately fuel the
      discovery of newer applications of robotic systems in urologic surgery. Herein we
      provide an overview of the history, development, and applications of robotics in
      surgery with a focus on urologic surgery.

PMID- 16882040
TI  - A phenotypic recessive, post-entry block in rabbit cells that results in aberrant
      trafficking of HIV-1.
AB  - Rabbit cells are poorly permissive to HIV-1 infection, but little is known about
      the nature of this block. Here, we show that the block to infection is mainly at
      the level of reverse transcription (RT), is independent of the cell receptor used
      by the virus for entry, cannot be effectively saturated with high doses of virus
      or virus-like particles, and has a recessive phenotype in human-rabbit
      heterokaryons. RT complexes (RTCs) extracted from human and rabbit cells have
      different densities but are both competent for RT in an in vitro endogenous
      assay. Cell fractionation showed that HIV-1 is trafficked in a different way in
      human and rabbit cells and that correct intracellular trafficking is linked to
      efficient RT and high infectivity in vivo. Viral DNA accumulated in rabbit cell
      nuclei only at a later stage and failed to associate with chromatin, suggesting a
      further block prior to integration. Our data point to the existence of cellular
      factors regulating the early stages of intracytoplasmic and possibly intranuclear
      HIV-1 trafficking.

PMID- 16882044
TI  - High incidence of and risk factors for metachronous bilateral upper tract
      urothelial carcinoma in Taiwan.
AB  - AIM: Urothelial carcinoma (UC) can occur multifocally in the whole urothelium. A
      higher rate of bilateral metachronous upper tract (UT) UC was noted in Taiwan.
      The incidence and risk factors were largely unknown and hence were explored in
      the study. METHODS: From January 1977 through June 2003, 462 patients with
      unilateral UT-UC were studied retrospectively. The cumulative incidence of
      contralateral recurrence was analysed with the Kaplan-Meier analysis. Potential
      risk factors for contralateral recurrence including age, smoking, bladder cancer,
      renal function, diagnostic year etc. were evaluated with the log-rank test.
      Independent risk factors were identified by using the Cox regression analysis.
      RESULTS: The median follow-up time was 34 months (6-337). Among the 462 patients,
      52 (11.3%) developed metachronous contralateral UC. The 2, 5, and 10-year
      contralateral disease-free survivals were 93.5%, 84.0%, and 75.7%, respectively.
      The median time to contralateral recurrence was 31.0 months. With the univariate
      analysis, only poor renal function (serum creatinine < or > OR =2.0 mg/dL, P <
      0.001) and late diagnostic year (before or after 1990, P < 0.001) were risk
      factors for contralateral recurrence. In the multivariate analysis, poor renal
      function (hazard ratio: 2.98; 95% confidence interval: 1.67-5.33; P < 0.001) and
      late diagnostic year (hazard ratio: 4.27; 95% confidence interval: 1.71-10.65; P
      = 0.002) remained independent risk factors. CONCLUSIONS: The incidence of
      metachronous UT-UC is high in Taiwan. Patients who had either chronic renal
      insufficiency or a disease diagnosed after 1990 had a higher risk of
      contralateral recurrence.

PMID- 16882045
TI  - Nutcracker phenomenon: a new diagnostic method of multislice computed tomography
      angiography.
AB  - OBJECTIVE: We evaluated 3-D computed tomography angiography (3-D CTA) in the
      diagnosis of the nutcracker phenomenon, and its significance in postoperative
      follow up. PATIENTS AND METHODS: Three-dimensional CTA was used to compare the
      anatomical relations of the left renal vein with the aorta and the superior
      mesenteric artery in patients with the nutcracker phenomenon and in a control
      group. Four patients with the nutcracker phenomenon received a surgical procedure
      of the transposition of the left renal vein. The 3-D CTA was used for all
      patients during postoperation follow-up testing. RESULTS: The 3-D CTA showed a
      compression of the left renal vein between the aorta and the superior mesenteric
      artery (SMA) and the abnormal acute angle between them. The angles and distances
      between the SMA and the aorta were 39.3 +/- 4.3 degrees and 3.1 +/- 0.2 mm in the
      patient groups and 90 +/- 10 degrees and 12 +/- 1.8 mm in the control groups,
      respectively. Differences in angles and distances were statistically significant
      between the two groups (P < 0.05). Surgical transposition of the left renal vein
      was performed successfully. Postoperative 3-D CTA revealed the distance between
      the SMA and the aorta was nearly normal. CONCLUSION: The reconstruction imaging
      of the renal vein by means of 3-D CTA revealed that unusual hematuria was due to
      compression of the left renal vein; therefore it may be a useful alternative
      imaging technique instead of conventional examinations. The non-invasive 3-D CTA
      may be a useful tool in the diagnosis of the nutcracker phenomenon and follow-up
      testing.

PMID- 16882046
TI  - Challenge of percutaneous nephrolithotomy in patients with spinal neuropathy.
AB  - OBJECTIVE: To assess the technical difficulties, associated complications and
      stone clearance rates in patients with spinal neuropathy undergoing percutaneous
      nephrolithotomy. METHODS: Twenty-nine patients with spinal neuropathy underwent
      percutaneous nephrolithotomy in the two centers studied between October 1995 and
      January 2002. They were nine patients with traumatic spinal cord injury, 10
      patients with spina bifida and 10 with other heterogeneous causes for their
      spinal neuropathy. The group included 12 men and 17 women, with an average age of
      44 years (14-80). Patients' medical records were reviewed retrospectively for
      data relating to their renal lithiasis. RESULTS: A total of 39 percutaneous
      nephrolithotomy procedures were undertaken on 32 kidneys. Thirteen procedures
      were for staghorn calculi. Preoperatively, eight kidneys required nephrostomy and
      5 J stent decompression. The average American Society of Anesthesiologists (ASA)
      score was 3, and one patient had percutaneous nephrolithotomy performed under
      local anaesthetic as the risk of general anaesthetic was felt to be too high. The
      associated morbidity and mortality in this group is significant. There were two
      postoperative deaths. Major complications were associated with three procedures,
      and consisted of seizures, aspiration pneumonia and pressure necrosis. Nine
      patients experienced minor complications including fever, hypotension and
      nephrostomy site leakage. Nine patients required intensive therapy unit care
      postoperatively and the average hospital stay for the group was 13.32 days. Only
      18 (62%) patients were rendered stone-free from their initial percutaneous
      nephrolithotomy. Seven patients required a further procedure for stone clearance:
      four underwent extracorporeal shock-wave lithotripsy, two ureteroscopy and one
      nephrectomy. CONCLUSIONS: Patients with spinal neuropathy and renal lithiasis
      pose a significant operative challenge. Technical difficulties and potential
      complications should be considered carefully before undertaking percutaneous
      nephrolithotomy in these patients.

PMID- 16882047
TI  - Percutaneous cryoablation of renal cell carcinoma guided by horizontal open
      magnetic resonance imaging.
AB  - BACKGROUND: Cryoablation is a treatment option for some patients with small
      exophytic lesions of the kidney. The purpose of this study is to determine the
      feasibility, safety, and intermediate-term treatment outcome of percutaneous
      cryoablation of renal cell carcinoma guided by horizontal open magnetic resonance
      imaging (MRI). METHODS: We prospectively used cryoablation to treat 13 patients
      with radiographically confirmed enhancing small, solid renal tumors (< or =4.8
      cm). An argon gas-based cryoablation system was used. One to four cryoprobes with
      2 or 3-mm diameters were placed percutaneously into the tumor under local
      anaesthesia and MRI guidance. Ice ball dimensions were monitored by 2-D MR
      images. Double freeze-thaw cycles were conducted throughout the procedure. After
      successful cryoablation, patients were followed on a regular basis to evaluate
      the treatment's clinical outcome. RESULTS: Median follow up from time of
      procedure is 35 months (range, 28-42). In all cases the entire procedure was
      accomplished without significant morbidity or complications. A mild
      retroperitoneal hematoma, which subsided spontaneously, was noted in one patient.
      Follow-up dynamic computed tomography (CT) at 3 months after operation confirmed
      the absence of enhancement in resolved tumor masses for 11 of 13 cases. None of
      these 11 patients had clinical evidence of recurrent disease at last follow up.
      The remaining two patients had lesions with some enhanced areas. Subsequent
      partial nephrectomy histologically confirmed the presence of vital tumor in,
      respectively, the center and the periphery of the residual masses. One of these
      patients developed multiple lung and ipsilateral adrenal metastases 13 months
      after surgical resection. CONCLUSIONS: Percutaneous cryoablation of small renal
      cell carcinomas under horizontal open MRI guidance appears to be safe and
      feasible. An intermediate-term follow up continues to demonstrate efficacy in
      most patients; however, a few patients experience incomplete ablation with risk
      of treatment failure. The ideal candidates for this procedure still need to be
      determined in longer follow up with diligent observation.

PMID- 16882048
TI  - Renal cryoablation: still experimental?

PMID- 16882049
TI  - Stenting versus non-stenting after non-complicated ureteroscopic manipulation of
      stones in bilharzial ureters.
AB  - BACKGROUND: Stents were used routinely after ureteroscopy to prevent
      postoperative ureteral obstruction. However, because of the recognized
      complications of stents, non-stenting is the new trend after uncomplicated
      ureteroscopy. The wall of the bilharzial ureter is characteristically thick and
      may be calcified. The aim of this study is to see if the non-stenting trend could
      be applied to ureteroscopic manipulation of stones in bilharzial ureters.
      PATIENTS AND METHODS: In this prospective study, 56 patients, with evidence of
      bilharzial lesions in the urinary tract, undergoing ureteroscopy for distal
      ureteral stones were included. After successful uncomplicated stone fragmentation
      and extraction, patients were randomized into two groups. Group A includes 28
      patients in whom double J 6-Fr polyurethane stents were placed for 3 weeks. Group
      B includes 28 non-stented patients. Postoperative fever, loin pain, lower urinary
      tract symptoms and change in the degree of hydronephrosis were reported. RESULTS:
      There was no significant difference in the mean age of patients and stone size in
      both groups. The mean operative time was 43 +/- 14 min in group A and 38 +/- 11
      in group B. There was no significant difference in the mean loin pain score, in
      the first postoperative 48 h, in both groups (4.4 +/- 0.8 in group A and 4.9 +/-
      0.5 in group B). Patients in group A had, significantly, more flank pain with
      voiding (P < 0.01), voiding pain (P = 0.04), frequency (P = 0.01) and urgency (P
      = 0.04). Radiologic follow-up was available for 24 patients in group A and 23
      patients in group B at the 3-month visit. Hydronephrosis had improved in all
      patients, in both groups, with no evidence of ureteral stricture. CONCLUSION:
      Routine placement of stents after uncomplicated ureteroscopy for distal ureteral
      stones is unnecessary in bilharzial ureters. Moreover, it might be unadvisable
      because lower urinary tract symptoms and voiding loin pain are more in patients
      with ureteral stents and hydronephrosis is equally improved in stented and non
      stented patients.

PMID- 16882050
TI  - Clinical outcome of tubeless cutaneous ureterostomy by the Toyoda method.
AB  - AIM: Cutaneous ureterostomy is the least invasive method of urinary diversion,
      but it carries a risk of stomal stenosis. We retrospectively examined the long
      term outcome of tubeless cutaneous ureterostomy by the Toyoda method. METHODS:
      Since 1983, the Toyoda cutaneous ureterostomy has been performed in 97 patients
      (169 renal units) with a minimum follow up of 3 months. The ureteral patency rate
      was reviewed according to whether the stomal type was single (one ureter, one
      stoma) or double-barrel (two ureters, one stoma). RESULTS: After a median follow
      up of 23 months (range 3 to 169), a tubeless condition was achieved in 102 (82%)
      of 124 renal units associated with double-barrel stoma and in 35 (78%) of 45
      renal units associated with single stoma. Although mild to moderate
      hydronephrosis was observed in 19% of patients, serum creatinine levels did not
      change after a minimum of 12 months after surgery (median 35). CONCLUSIONS: A
      high ureteral patency rate was achieved with cutaneous ureterostomy using the
      Toyoda method. This procedure, especially double-barrel stomal creation, is a
      reasonable alternative to other forms of urinary diversion in patients at high
      risk.

PMID- 16882051
TI  - Virtual reality ureteroscopy simulator as a valid tool for assessing
      endourological skills.
AB  - AIM: Virtual reality (VR) simulators are now commercially available for various
      surgical skills training. The Uro Mentor VR Ureteroscopy Simulator by Symbionix
      is one system that may revolutionize the way we assess and teach surgical
      residents. Surgical educators may no longer have to depend on the operating room
      as the sole venue for teaching residents technical skills. We validated
      performance on this new system with previously developed assessment tools and
      compared it to performance on a high fidelity ureteroscopy bench model. METHODS:
      Urology residents (n = 16) were assessed on their ability to perform cystoscopy,
      guidewire insertion, semirigid ureteroscopy and basket extraction of a distal
      ureteric stone on the VR simulator. A blinded examiner assessed subject
      performance using a checklist, global rating scale and a pass/fail rating. In
      addition, computer-generated parameters including time to complete task, scope
      and instrument trauma and the number of attempts to insert a guidewire were
      analysed. Performance on the VR simulator was compared to performance on a high
      fidelity ureteroscopy bench model. RESULTS: Senior residents (n = 8) scored
      significantly higher on their global rating scale (29.4 +/- 2.5 vs 20.8 +/- 0.9,
      P = 0.005), checklist (19.1 +/- 1.1 vs 15.2 +/- 0.9, P = 0.02), pass/fail rating
      (chi(2) = 7.3, P = 0.007) and required less time to complete the task (352.9 +/-
      55.7 s vs 576.8 +/- 67.4 s., P = 0.02) than the junior residents (n = 8) on the
      VR simulator. Junior residents also had a significantly higher incidence of scope
      trauma (4 vs 0.6, P = 0.02). No significant differences were noted in instrument
      trauma and the number of attempts to insert the guidewire. Global rating scale
      performance on the VR simulator correlated well to performance on the high
      fidelity ureteroscopy bench model (r = 0.7, P = 0.002) as did time to complete
      task (r = 0.7, P = 0.004). CONCLUSIONS: The Uro Mentor VR Ureteroscopy Simulator
      is a useful tool in assessing resident endourological skills. Performance on the
      VR simulator is comparable to a validated high fidelity ureteroscopy bench model.
      Future studies will assess the utility of VR simulators in surgical skills
      training.

PMID- 16882052
TI  - Endometriosis of the urinary tract in women of reproductive age.
AB  - AIM: We present our experience with diagnosing and treating 22 cases of urinary
      tract endometriosis in women of reproductive age. PATIENTS AND METHODS: From
      January 2001 to January 2003, 22 women of reproductive age (mean age 34.8 years)
      were diagnosed suffering from endometriosis of the urinary tract. We used the
      Endoscopic Endometriosis Classification (EEC) for assessing the stage of
      endometriosis. RESULTS: Endometriosis was present in the bladder, the lower third
      of the ureter, and in a postnephrectomy ureteral stump in 15 (68.1%), six (27.2%)
      and one (4.5%) cases, respectively. The EEC classification revealed stages I, II,
      III and IV in four (18.1%), one (4.5%), one (4.5%), and 16 (72.7%) patients,
      respectively. Urinary symptoms were present in 14 (63.6%) patients. For the
      treatment of bladder endometriosis, 10 patients underwent partial cystectomy,
      while the remaining five patients were treated with transurethral resection. In
      four patients ureterolysis was performed, by laparoscopy in two cases and by open
      surgery in the other two cases. Ureterectomy and re-implantation with bladder
      psoas hitching took place in six patients. In the case of endometriosis of the
      ureteral stump, open surgical excision took place. During the mean follow-up
      period of 20 months (range 16-40) no long-term complication or relapse was
      diagnosed. CONCLUSIONS: Bladder and ureteral endometriosis should be considered
      in women of reproductive age with non-specific urinary tract or abdominal
      symptoms, and surgical treatment is recommended.

PMID- 16882053
TI  - Effect of a 'centralized intensive education system' for clean intermittent self
      catheterization in patients with voiding dysfunction who start catheterization
      for the first time.
AB  - BACKGROUND: This study evaluated the effects of a 'centralized intensive
      education system' (CIES) in terms of acquiring a proper clean intermittent self
      catheterization (CISC) technique by patients with voiding dysfunction. METHODS:
      Between March 2002 and March 2003, we prospectively and consecutively enrolled
      132 hospitalized patients who learnt and started CISC for the first time due to
      voiding dysfunction. Patients were enrolled either of two groups (the CIES group
      vs the 'individualized ward education system'[IWES] group) at the time of the
      urologic consultation for voiding dysfunction. Out of 132 patients who enrolled
      in the study, 112 (45 males and 67 females, mean age 57.3 with a range of 18-81)
      were included in the primary analyses. The questionnaire was applied immediately
      before discharge. RESULTS: There were similar patient demographics and clinical
      parameters for the CIES (n = 62) and the IWES groups (n = 50). Of 10 items
      including the methodology of CISC, six items discriminated significantly in favor
      of the CIES (P < 0.05). The patient satisfaction with CISC education was
      significantly different for the two groups in terms of response to the
      questionnaire. The CIES group was found to be more satisfied with the education
      received than the IWES group (P < 0.05). Moreover, the number of trials to gain
      confidence to perform CISC in CIES group was significantly fewer than that of
      IWES group (P < 0.001). CONCLUSION: Our results demonstrate that CIES might be a
      superior training program for the patients with voiding dysfunction to acquire a
      proper CISC technique to the conventional IWES.

PMID- 16882054
TI  - Prostate-specific antigen adjusted for the transition zone volume as a second
      screening test: a prospective study of 248 cases.
AB  - AIM: This study was conducted to verify the effectiveness of prostate-specific
      antigen adjusted for the transition zone volume (PSATZ), and its availability as
      a second screening test for prostate cancer detection. MATERIALS AND METHODS:
      Total prostate-specific antigen (PSA) and free PSA was measured in male patients
      who visited our outpatient department for voiding difficulty or screening for
      prostate cancer. Patients who had an intermediate PSA level between 4.0 and 10.0
      ng/mL, with an apparently normal prostate on a digital rectal examination, were
      enrolled. PSATZ, free-to-total PSA ratio (F/T ratio) and PSA density (PSAD) were
      calculated and statistical comparisons between biopsy-positive (cancer) and
      biopsy-negative patients (benign) were conducted. RESULTS: Of 248 patients, 51
      (20.6%) had prostate cancer and 197 (79.4%) had benign prostatic hyperplasia
      (BPH) on pathologic examination. Mean PSA, PSAD, F/T ratio and PSATZ were 7.48 +/
      1.77 ng/mL, 0.23 +/- 0.09 ng/mL per mL, 0.14 +/- 0.08 and 0.71 +/- 0.44 ng/mL
      per mL in patients with prostate cancer and 6.59 +/- 1.60 ng/mL, 0.16 +/- 0.07
      ng/mL per mL, 0.21 +/- 0.11 and 0.36 +/- 0.30 ng/mL per mL in patients with
      benign, respectively. Receiver operating characteristics (ROC) curve analysis
      demonstrated that PSATZ predicted the biopsy outcome better than F/T ratio. With
      a cut-off value of 0.37 ng/mL per mL, PSATZ had a sensitivity of 74.5% and a
      specificity of 72.6% for predicting prostate cancer. The maximal cut-off value
      that preserves 100% of sensitivity was 0.2, and at this cut-off value, 16.1% of
      unnecessary biopsies could be reduced. CONCLUSIONS: Prostate-specific antigen
      adjusted for the transition zone volume may be more useful than other strategies
      in detecting prostate cancer in patients with intermediate PSA levels of 4.0-10.0
      ng/mL. It can be used as a second screening test to reduce unnecessary biopsy.

PMID- 16882055
TI  - Clinical significance of urinary white blood cell count and serum C-reactive
      protein level for detection of non-palpable prostate cancer.
AB  - AIM: The clinical significance of the urinary white blood cell (U-WBC) count and
      serum C-reactive protein (CRP) level was evaluated in an effort to improve the
      efficiency of prostate biopsies. METHODS: We enrolled 228 consecutive patients
      with serum prostate-specific antigen (PSA) ranging from 3.0 to 20.0 ng/mL, normal
      digital rectal examination findings, and who underwent prostate biopsies between
      January 2001 and August 2004. Of these, 157 patients had histologically confirmed
      benign prostatic disease and the remaining 71 patients had prostate cancer.
      Patients with a pretreatment U-WBC count < or =3 or >3/high power field were
      defined as non-pyuria and pyuria, respectively. The patients were also separated
      into two groups based on the serum CRP level prior to biopsy. Several clinical
      factors were compared among these subgroups. RESULTS: Inflammation was
      histologically detected at rates of 58.1% and 34.1% in the pyuria and non-pyuria
      groups, respectively (P = 0.0014). The rates of cancer detection were
      significantly lower in the pyuria, than in the non-pyuria group (P = 0.0384). The
      cancer detection rates did not significantly differ according to serum CRP levels
      prior to biopsy. CONCLUSION: The U-WBC count appears to be a reliable indicator
      of minute prostatic inflammation. The serum PSA level was elevated in patients
      with asymptomatic prostatitis. Counting U-WBC is a simple, convenient and non
      invasive method that should be valuable part of routine urological examinations.

PMID- 16882056
TI  - Baseline health-related quality of life in the management of prostate cancer.
AB  - OBJECTIVE: The purpose of this study was to clarify characteristics of baseline
      health-related quality of life (HRQOL) during the diagnostic process of prostate
      cancer. METHODS: A prospective study was conducted to measure HRQOL in a cohort
      of 141 patients in whom prostate cancer was suspected and prostate biopsy was
      scheduled, using both generic and disease-specific HRQOL measures (SF-36, UCLA
      Prostate Cancer Index) at two points: before prostate biopsy (prediagnosis) and
      after giving biopsy results (postdiagnosis). Seventy-three patients were
      diagnosed with prostate cancer and 68 were not. RESULTS: Compared to age-gender
      adjusted population norms, patients demonstrated better physical function (PF)
      and worse mental health (MH). Characteristic age-related changes were found in PF
      and sexual function (SXF); however, disease stage exhibited no relevant effects
      in HRQOL. No significant difference was detected between pre- and postdiagnosis
      SF-36 and UCLA-PCI scores. CONCLUSION: The present study discovered no relevant
      impact of the diagnostic process of prostate cancer on baseline HRQOL using SF-36
      and UCLA-PCI. Combined with results of previous studies, it is supportive of
      regarding pretreatment levels of HRQOL as the baseline.

PMID- 16882057
TI  - Significance of electrostimulation in detecting neurovascular bundle during
      radical prostatectomy.
AB  - OBJECTIVE: The reported rate of erectile dysfunction after nerve-sparing
      prostatectomy varies according to physicians. Because exact preservation of the
      neurovascular bundle (NVB) solely depends on the judgment of the physician, he or
      she should try to correctly identify the NVB and also avoid neurophysiologic
      injury of the NVB during the procedure. The purpose of the present study is to
      assess the status of the NVB preservation by physician's judgment at the
      operation, the changes in intracavernous pressure related to intraoperative
      electrical stimulation and postoperative histopathological examination. PATIENTS
      AND METHODS: Thirty-eight patients who underwent nerve-sparing radical
      prostatectomy judged by intraoperative electrical stimulation of the NVB were
      included in this study. Bilateral, unilateral and non-nerve-sparing procedures
      were performed in 18, 17, and 3 cases, respectively. The NVB preservation
      evaluated by intraoperative physician's judgment was compared to that evaluated
      by postoperative histopathological examination. Furthermore, the NVB preservation
      evaluated by intraoperative electrical stimulation was compared to that by
      physician's judgment and postoperative histopathological examination. RESULTS:
      For 68 of 76 NVB (89.5%), intraoperative subjective judgment and
      histopathological assessment were identical. For 66 of 76 NVB (86.8%), electrical
      stimulation findings and the physician's judgments were identical, and for 70 of
      76 NVB (92.1%), electrical stimulation findings and histopathological findings
      were identical. CONCLUSION: Even if physicians are convinced of a successful
      nerve-sparing procedure, there are some cases in which the NVB is not preserved
      accurately or neurophysiological damage is suffered. Therefore, intraoperative
      electrical stimulation of the NVB as well as the cavernosal nerve is very useful
      in evaluation of NVB preservation.

PMID- 16882058
TI  - Comparison of 25 and 75 mg/day naftopidil for lower urinary tract symptoms
      associated with benign prostatic hyperplasia: a prospective, randomized
      controlled study.
AB  - BACKGROUND: The present study investigated the efficacy, safety, and utility of
      starting an alpha(1d)-selective antagonist, naftopidil, at 75 or 25 mg/day in
      patients with lower urinary tract symptoms (LUTS) associated with benign
      prostatic hyperplasia (BPH). METHODS: In this prospective comparative study, the
      subjects comprised 153 patients with LUTS associated with BPH. Patients were
      randomized to receive either 25 mg/day (Group LD) or 75 mg/day (Group HD) of
      naftopidil for 4 weeks. The lower urinary tract disease symptom score (LUTDSS),
      the International Prostate Symptom Score (IPSS), the Quality of life assessment
      index, the maximum flow rate (Q(max)), and the residual urine volume were
      compared between the groups. RESULTS: In both groups, the LUTDSS and the IPSS
      were significantly improved at the endpoint and no significant intergroup
      differences were identified. However, the improvement in the Q(max) was
      significantly better for Group HD than for Group LD. The overall efficacy did not
      differ significantly between the groups. The degree of improvement in voiding
      symptoms and LUTDSS among patients with moderate symptoms was significantly
      greater for Group HD than for Group LD. The frequency of adverse reactions did
      not differ significantly between the groups. CONCLUSIONS: Starting administration
      at 75 mg/day rather than 25mg/day is helpful for LUTS associated with BPH for
      patients with moderate symptoms, particularly in improving voiding symptoms. The
      75 mg/day administration was considered to be a recommendable therapeutic dose in
      some patients.

PMID- 16882059
TI  - A proposal of subcategorization of bacterial prostatitis: NIH category I and II
      diseases can be further subcategorized on analysis by therapeutic and
      immunological procedures.
AB  - AIM: We propose preliminarily that acute (category I of the NIH consensus
      definition) and chronic prostatitis (category II) can be subcategorized into
      primary and recurrent diseases based on the precise analysis of the clinical
      course and the immunological parameters in prostatic secretions of our cases.
      METHODS: Five patients with stone-free, acute febrile prostatitis and nine
      patients with acute episodes of afebrile urinary infection were included. The
      expressed prostatic secretions (EPS) were collected soon after the acute
      illnesses subsided after medication administration and they were examined
      microscopically, bacteriologically, and serologically. First-line medications
      were cefem antibiotics with conventional doses for febrile cases and low doses
      for afebrile cases. They were administered for at least 2 weeks. Second-line
      conventional medication with sulfamethoxazole-trimethoprim or levofloxacin was
      given only to the patients in whom remaining prostatic infections were revealed.
      RESULTS: The first-line medications were successful in all patients and they
      promptly became asymptomatic in 1 week. All the EPS were infected except for two
      afebrile cases. Prostatic infections were eradicated by second-line conventional
      medications. In a patient with afebrile prostatitis whose EPS were free of
      macrophages and immunoglobulin (Ig)M, the eradication of prostatic pathogens was
      achieved without second-line antibacterial medication. CONCLUSIONS: Bacterial
      prostatitis could be classified into primary and recurrent chronic infections in
      each of the febrile (category I) and afebrile (category II) illnesses. A cefem
      regimen in varying doses was a clue for differential diagnosis as it did not
      affect the pathogens in the prostatic ducts or acini unless heavy urine reflux
      occurred in the ductal draining systems. Macrophages and immunoglobulins,
      especially IgM, in the EPS were useful immunological parameters to differentiate
      primary and recurrent infections of the prostate. Fluoroquinolones or
      sulfamethoxazole-trimethoprim should not be employed in acute urinary infections
      in male patients until the confirmation of prostatic infection to avoid
      injudicious use of them, which might cause an increasing prevalence of resistant
      uropathogens in the community. The evacuation of the prostate by repetitive
      massage seemed to be effective to enhance the prompt eradication of pathogens
      from the prostatic tissue and to keep patients asymptomatic throughout the course
      of the disease by preventing tissue pressure elevation.

PMID- 16882060
TI  - Effect of prostate manipulation on the serum levels of complexed prostate
      specific antigen and total prostate-specific antigen.
AB  - BACKGROUND: Recently there has been considerable interest in complexed prostate
      specific antigen (cPSA) as an alternative to total PSA (tPSA). Data regarding the
      variations of cPSA are limited. We performed a prospective study using different
      forms of prostate manipulation to demonstrate and compare variations between cPSA
      and tPSA. METHODS: The study included 113 men, 34 of whom had a digital rectal
      examination, 28 had a flexible cystoscopy, 17 had a rigid cystoscopy, 21 had a
      prostate biopsy, and 13 underwent a transurethral resection of the prostate
      (TURP). Blood samples were taken before and after manipulation for measurement of
      tPSA and cPSA. RESULTS: There was a statistically significant difference in the
      cPSA and tPSA before and after manipulation, with the exception of cystoscopy. On
      review of the data, it was clear that not all changes were clinically
      significant. The mean differences were greater for tPSA than for cPSA for all
      procedures. This was most apparent following prostate biopsy and TURP. Regression
      analysis also showed that cPSA and tPSA were affected differently by prostate
      manipulation. CONCLUSION: Our results demonstrate that cPSA is less prone to
      variations when compared to tPSA.

PMID- 16882061
TI  - Maximum tumor diameter is a simple and valuable index associated with the local
      extent of disease in clinically localized prostate cancer.
AB  - BACKGROUND: The present study was undertaken to investigate the association of
      pathological features, including the total tumor volume (TTV), maximum tumor area
      (MTA), and maximum tumor diameter (MTD), with the local extent of disease in
      clinically localized prostate cancer. METHODS: Serial whole sections of the
      prostate from 164 patients who underwent radical prostatectomy for localized
      prostate cancer were investigated. The correlations between the indicators of
      tumor size, including the TTV, MTA, and MTD, and other pathological parameters
      were evaluated. RESULTS: The MTD, MTA, and TTV were significantly correlated with
      each other. Multivariate stepwise logistic regression analysis indicated that the
      Gleason score, perineural invasion, microvascular invasion, and MTD were
      significant independent parameters associated with extraprostatic disease.
      CONCLUSION: The histological tumor grade, perineural invasion, microvascular
      invasion, and tumor size were correlated with the local extent of disease. The
      MTD, a simple, easy, and inexpensive parameter, is a more significant
      pathological feature associated with the local extent of disease than the MTA or
      TTV.

PMID- 16882062
TI  - Effect of sildenafil on arterial stiffness, as assessed by pulse wave velocity,
      in patients with erectile dysfunction.
AB  - BACKGROUND: The problems of patients with erectile dysfunction have been
      recognized, leading to the emergence of sildenafil, which has led to successful
      treatment in many cases. The purpose of this study is to examine the effect of
      sildenafil on the pulse wave velocity of patients with erectile dysfunction.
      METHODS: Fifteen patients with erectile dysfunction were enrolled for this study.
      The brachial/ankle pulse wave velocity was determined before dosing and at 30,
      60, 120, and 180 min after dosing with 25 or 50 mg of sildenafil citrate.
      Concurrently, the changes in blood pressure, heart rate, and brachial/ankle pulse
      wave velocity were measured. For the consideration of revised brachial/ankle
      pulse wave velocity by blood pressure, the systolic blood pressure-derived
      brachial/ankle pulse wave was also investigated, and we classified and examined
      those results with and without risk factors for arteriosclerosis. RESULTS: The
      systolic blood pressure decreased significantly at 60 min after dosing compared
      with the placebo control. The heart rate decreased at 120 min after dosing
      compared with the placebo control but that decrease was not significant. The
      brachial/ankle pulse wave velocity transiently decreased at 30 or 60 min after
      dosing compared with the placebo control, but the decrease was not significant;
      however, the systolic blood pressure-derived brachial/ankle pulse wave velocity
      decreased significantly. In those patients with risk factors for
      arteriosclerosis, the pulse wave velocity decreased significantly. CONCLUSION: In
      patients with erectile dysfunction who were administered sildenafil, the pulse
      wave velocity, along with blood pressure, tended to decrease transiently after
      dosing. There is a possibility that sildenafil affects the improvement of
      erectile dysfunction via the decrease of pulse wave velocity, especially in
      patients with risk factors for arteriosclerosis.

PMID- 16882063
TI  - Fournier's gangrene: report of thirty-three cases and a review of the literature.
AB  - BACKGROUND: Fournier's gangrene (FG) is an extensive fulminant infection of the
      genitals, perineum or the abdominal wall. The aim of this study is to share our
      experience with the management of this difficult infectious disease. METHODS:
      Thirty-three male patients were admitted to our clinic with the diagnosis of FG
      between February 1988 and December 2003. The patient's age, etiology and
      predisposing factors, microbiological findings, duration of hospital stay,
      treatment, and outcome were analyzed. The patients were divided into two groups.
      The first 21 patients (Group I) were treated with broad-spectrum triple
      antimicrobial therapy, broad debridement, exhaustive cleaning, and then they
      underwent split-thickness skin grafts or delayed closure as needed. The other 12
      patients (Group II) were treated with unprocessed honey (20-50 mL daily) and
      broad-spectrum triple antimicrobial therapy without debridement. Their wounds
      were cleaned with saline and then dressed with topical unprocessed honey. The
      wounds were inspected daily and the honey was reapplied after cleaning with
      normal saline. Then, the patients' scrotum and penis were covered with their own
      new scrotal skin. The mean age of the patients was 53.9 +/- 9.56 years (range =
      23-71). RESULTS: The source of the gangrene was urinary in 23 patients, cutaneous
      in seven patients, and perirectal in three patients. The predisposing factors
      included diabetes mellitus for 11 patients, alcoholism for 10 patients,
      malnutrition for nine patients, and medical immunosuppression (chemotherapy,
      steroids, malignancy) for three patients. The mean duration of hospital stay was
      41 +/- 10.459 (range = 14-54) days. Two patients in Group I died from severe
      sepsis. The clinical and cosmetic results were better in Group II than Group I.
      CONCLUSION: Necrotizing fasciitis of the perineum and genitalia is a severe
      condition with a high morbidity and mortality. Traditionally, good management is
      based on aggressive debridement, broad-spectrum antibiotics, and intensive
      supportive care but unprocessed honey might revolutionize the treatment of this
      dreadful disease by reducing its cost, morbidity, and mortality.

PMID- 16882064
TI  - Foreskin development before adolescence in 2149 schoolboys.
AB  - BACKGROUND: We examined the external genitalia of 2149 elementary schoolboys in
      the suburban area of Taichung in Taiwan for an understanding of foreskin
      development before adolescence. METHODS: The study's subjects comprised 692 first
      grade boys, 725 fourth-grade boys, and 732 seventh-grade boys. The foreskin's
      condition was classified as: type I (normal prepuce), type II (adhesion of
      prepuce), type III (partial phimosis), type IV (phimosis) and type V (circumcised
      foreskin). Other abnormalities of the genitalia also were recorded. All of the
      examinations were performed by the same urologist. RESULTS: The incidence of type
      I foreskin was 8.2% in first-grade boys, 21.0% in fourth-grade boys, and 58.1% in
      seventh-grade boys. The incidence of type IV foreskin was 17.1% in first-grade
      boys, 9.7% in fourth-grade boys, and 1.2% in seventh-grade boys. Only one boy had
      balanoposthitis. Other abnormalities included inguinal hernia (n = 2), hydrocele
      (n = 12), cryptorchitism (n = 8), varicocele (n = 22), and subcoronal-type
      hypospadia (n = 1). CONCLUSIONS: Physiological phimosis declines with age. Most
      boys with phimosis in this study did not require treatment.

PMID- 16882065
TI  - Possible correlation between polymorphism in the tumor necrosis factor-beta gene
      and the clinicopathological features of bladder cancer in Japanese patients.
AB  - OBJECTIVES: In a variety of cancers, several polymorphisms of the tumor necrosis
      factor (TNF) genes have been reported to result in different clinical outcomes.
      We investigated whether a polymorphism of the TNF gene is associated with a
      susceptibility to bladder cancer and its disease status. METHODS: Polymorphisms
      in the TNF-alpha gene promoter (-308 bp) and the NcoI site in the first intron of
      the TNF-beta gene were analyzed in 141 Japanese patients with bladder cancer and
      173 Japanese controls by polymerase chain reaction-restriction fragment length
      polymorphism. The correlations between the polymorphisms of the TNF genes and the
      clinicopathological features were analyzed. RESULTS: The number of cases and
      controls with TNF-alpha2 was too small to be assessable. In contrast, the TNF
      beta1/2 genotype at the NcoI site in the first intron conferred a 1.71-fold
      increased risk of bladder cancer compared to the TNF-beta2/2 genotype. In the
      bladder cancer group, patients with the TNF-beta1 allele had a significantly
      higher risk for a high-grade tumor (grade 3) or carcinoma in situ (CIS) than
      those without the TNF-beta1 allele. Moreover, in the superficial bladder cancers,
      patients with the TNF-beta1 allele showed a significantly higher intravesical
      recurrence rate than those without the TNF-beta1 allele. CONCLUSION: This
      polymorphism in the TNF-beta gene appears to be associated with tumor occurrence
      and disease status, such as the tumor grade and the presence of CIS. Further
      study with an increased sample size is warranted.

PMID- 16882067
TI  - Renal cell carcinoma with non-islet cell tumor hypoglycemia.
AB  - We report a case of an elderly gentleman with renal cell carcinoma presenting
      with the rare entity of non-islet cell tumor hypoglycemia (NICTH). Non-islet cell
      tumor hypoglycemia syndrome is caused by the tumor producing insulin-like growth
      factor II, causing hypoglycemia. The syndrome is most commonly associated with
      very large fibromas or fibrosarcomas.

PMID- 16882066
TI  - Comparison of the effects of percutaneous and intraduodenal administration of
      oxybutynin on bladder contraction and salivation in rabbits.
AB  - AIM: As only a few basic animal experiments have assessed the usefulness of
      percutaneous application of oxybutynin, we compared the effects of percutaneous
      application and intraduodenal injection of oxybutynin on urinary bladder
      contraction accompanied by micturition in conscious rabbits and salivation in
      anesthetized rabbits. METHODS: Bladder contractions were induced by continuous
      infusion of saline (2 mL/min) into the bladder. Salivary secretion was induced by
      pilocarpine (0.1 mg/kg, i.v.). Oxybutynin was administered at 15 mg/animal, and
      the plasma concentrations of oxybutynin and N-desethyloxybutynin were measured by
      high-performance liquid chromatography to clarify the effective concentration.
      RESULTS: The intercontraction interval (ICI) was prolonged from 0.5 h after
      intraduodenal injection of oxybutynin, and this effect continued for 2 h. The ICI
      prolongation after percutaneous application of oxybutynin appeared at 2 h and
      continued throughout the 6-h experimental period. The saliva secretion induced by
      pilocarpine was inhibited to almost the same level by oxybutynin 3 h after
      intraduodenal injection and 6 h after percutaneous application. However, the sum
      of the plasma concentrations of oxybutynin and N-desethyloxybutynin rose steeply
      to a very high level within 20 min after oral administration instead of
      intraduodenal injection and decreased within 3 h to about half of the level
      evident 6 h after percutaneous application. CONCLUSION: We confirmed that
      percutaneous application of oxybutynin caused long-lasting ICI prolongation in
      our rabbit model, as compared with that after intraduodenal injection, and
      produced weaker inhibitory effects on saliva secretion because it did not cause
      steep elevation of the plasma concentration.

PMID- 16882068
TI  - Myxoma of the kidney.
AB  - A 62-year-old man had a right renal mass incidentally diagnosed by
      ultrasonography. Magnetic resonance imaging revealed a well-defined right renal
      mass with homogenous low-signal intensity on the T(1)-weighted pulse sequence and
      heterogeneous high-signal intensity on the T(2)-weighted pulse sequence. A right
      nephrectomy was performed. The histological examination showed a myxoma, which is
      a very uncommon neoplasm in the kidney. Eight cases have been reported
      previously.

PMID- 16882069
TI  - Spironolactone with ACE inhibitor is effective in gross hematuria caused by
      nephroptosis.
AB  - Gross hematuria caused by nephroptosis is difficult to treat and sometimes
      requires surgical treatment. We experienced a case of a 64-year-old woman with
      gross hematuria due to nephroptosis and glomerular thin basement membrane that
      showed remission of hematuria with the blockade of the renin-angiotensin
      aldosterone system with an angiotensin-converting enzyme inhibitor and
      spironolactone.

PMID- 16882070
TI  - Large renal aneurysm successfully treated by percutaneous embolization using
      detachable steel coils.
AB  - A 71-year-old man was referred to our hospital because of hematuria. A computed
      tomography scan showed a huge aneurysm (43 x 32 x 30 mm) in the right kidney. The
      patient was treated successfully with transcatheter arterial embolization (TAE)
      using detachable steel coils. At present, 1 year after TAE, the patient has no
      hematuria and hypertension. To our knowledge, this case is the second largest
      aneurysm treated successfully by TAE.

PMID- 16882071
TI  - Laparoscopic excision of a ureteral diverticulum.
AB  - Ureteral diverticula are a rare anomaly of the ureteral structure and were
      reported as case reports in the literature. We report an acquired ureteral
      diverticulum that was managed with laparoscopic resection. The clinical
      presentation is demonstrated and the follow-up image is illustrated. The
      laparoscopic application could be expanded to this area.

PMID- 16882072
TI  - Possibility of spontaneous seeding of transitional cell carcinoma of the ureter
      in renal tubules: another mechanism of transitional cell carcinoma dissemination.
AB  - Cancer cell seeding inside the urinary tract always has been considered one
      possible mechanism of the multicentric origin of transitional cell carcinoma
      (TCC). However, there is still no direct clinical evidence to prove that the
      natural seeding of TCC is a real event. To our knowledge, we report the first
      case of spontaneous seeding of TCC of the ureter in the renal tubules of a
      hydronephrotic kidney. The TCC nature of the intratubular tumor cells has been
      confirmed by the morphological appearance of them after hematoxylin and eosin
      staining and positive p53 immunohistochemical staining.

PMID- 16882073
TI  - Primary renal inflammatory malignant fibrous histiocytoma: a diagnostic
      challenge.
AB  - Renal inflammatory malignant fibrous histiocytoma (MFH) is an extremely rare
      lesion and is a great masquerader of common benign renal inflammatory lesions,
      especially xanthogranulomatous pyelonephritis (XGPN). The clinical presentation
      of mass with fever and peripheral leucocytosis (marked at times), and marked
      inflammatory, predominantly neutrophilic, infiltrate obscuring the malignant
      cells on histopathology, can lead to delay in the diagnosis of this poor
      prognostic malignant tumor. We present the case of a patient who underwent
      radical nephrectomy with a clinical diagnosis of renal malignancy, but
      histopathology showing XGPN. The patient showed an initial clinical response,
      only to recur two times, ultimately leading to a histological and
      immunohistochemical diagnosis of inflammatory MFH. The diagnosis, histology,
      therapeutic options and prognosis of this rare lesion are discussed.

PMID- 16882074
TI  - Bladder wall injury consequent to total hip replacement: delayed presentation.
AB  - Bladder injury, although rare, may be traumatic or iatrogenic. We report a
      patient with greatly delayed presentation of bladder injury after a total hip
      replacement.

PMID- 16882075
TI  - An unusual complication after a cystectomy: a case of iliac artery-neobladder
      fistula.
AB  - Iliac artery-neobladder fistula is very rare and only a few cases have been
      reported. The authors report a case of a 62-year-old man, diagnosed with a CT
      scan and an angiographic procedure and treated with a vascular endoprothesis
      placed through a percutaneous femoral access. The important role of early
      recognition is focussed on.

PMID- 16882076
TI  - Rupture of ectopic pregnancy implanted in the bladder.
AB  - A 34-year-old woman was diagnosed by ultrasound with a six-week ectopic pregnancy
      with implantation of the gestational sac in the bladder wall. She was initially
      treated with methotrexate 50 mg/m(2) i.m. Although a 22% reduction in the levels
      of beta-hCG was observed at first, there was a rupture of gestational sac. The
      patient underwent an emergency laparotomy with a resulting partial cystectomy,
      and made an uneventful recovery.

PMID- 16882077
TI  - Laparoscopic radical cystectomy and bilateral ureteric ligation for muscle
      invasive bladder cancer in a patient on hemodialysis.
AB  - Laparoscopic cystectomy and bilateral ureteric ligation were performed on a 52
      year-old woman with end-stage renal disease on hemodialysis (HD) for muscle
      invasive bladder cancer. Her volume of urine production was approximately 100
      mL/day. Excisions of the bladder and uterus with ligation of the bilateral ureter
      were conducted completely laparoscopically. Total operative time was 280 min and
      the amount of blood loss was 60 mL. No complications were seen perioperatively
      and no adverse events regarding ureteric ligation arose. HD was performed on the
      second postoperative day. At a 12-month follow-up, the patient showed no evidence
      of disease.

PMID- 16882078
TI  - Rare case of aggressive angiomyxoma presenting as a retrovesical tumor.
AB  - Aggressive angiomyxoma (AAM) is a rare mesenchymal benign tumor that
      preferentially involves the pelvic and perineal regions in relatively young
      females. We report here a rare case of AAM presenting as a retrovesical tumor in
      a male patient. A 59-year-old man undergoing abdominal ultrasound examination
      because of benign prostatic hyperplasia was found to have a retrovesical mass.
      Computed tomography and magnetic resonance imaging of the pelvis showed the
      retrovesical tumor to be 7.4 x 6.7 cm. The tumor was resected, and diagnosed
      histopathologically as AAM. The patient showed no recurrence 26 months after
      resection. Although the majority of retrovesical tumors are considered to be
      sarcoma or neurogenic tumor, AAM should also be recognized as a differential
      diagnosis.

PMID- 16882079
TI  - Invasive micropapillary carcinoma of the urinary bladder: an immunohistochemical
      study of neoplastic and stromal cells.
AB  - A 66-year-old man complained of hematuria. A cystoscopy revealed a non-papillary
      tumor and radical cystectomy was performed. Macroscopically, an ulcerative lesion
      was observed. Microscopically, the neoplasm showed a mixture of urothelial
      carcinoma, squamous cell carcinoma and micropapillary carcinoma.
      Immunohistochemically, micropapillary carcinoma cells were positive for
      cytokeratins 7 and 20, carcinoembryonic antigen and CA125. Additionally,
      myofibroblasts were distributed in a chicken-wire pattern in the stroma of
      micropapillary carcinoma. Subsequently, the patient died of carcinoma 1 year
      after the onset of symptoms. Our results support the previous hypothesis that
      bladder micropapillary carcinoma runs an aggressive clinical course and suggest
      that micropapillary carcinoma may show the glandular differentiation of
      urothelial carcinoma and show the stromal reaction by myofibroblasts resembling
      that of carcinoma in other anatomic sites.

PMID- 16882080
TI  - Dramatic decline in prostate-specific antigen by withdrawal of estramustine
      phosphate in hormone refractory prostate cancer.
AB  - Prostate-specific antigen (PSA) decline after discontinuation of estramustine
      phosphate (EMP) is extremely rare. We report a case with dramatic PSA decline
      after withdrawal of EMP. A patient with prostate cancer had been treated with
      luteinizing hormone-releasing hormone and EMP. After refractory, EMP was
      withdrawn. After withdrawal of EMP, PSA dramatically decreased from 214 ng/mL to
      3.71 ng/mL (98.5% decline) and remained low for more than 17 months. In
      association with PSA decline, lumbago and metastatic lesions improved. We should
      be aware of this phenomenon and the discontinuation of EMP is recommended in
      patients with rising PSA after an initial response to EMP.

PMID- 16882081
TI  - Occipital condyle syndrome guiding diagnosis to metastatic prostate cancer.
AB  - Occipital condyle syndrome (OCS) results from a unilateral occipital pain
      associated with an ipsilateral paresis of the 12th cranial nerve (hypoglossal),
      and is typically caused by metastasis of the skull base. OCS diagnosis occurred,
      in all cases described in the published literature, when metastatic prostate
      cancer (MPC) was previously known. We present a case of a patient whose initial
      manifestation of MPC was OCS. The patient was treated with complete hormonal
      blockade and non-steroidal anti-inflammatory drugs as opposed to locoregional
      radiotherapy applied in other cases. After 18 month follow-up, the patient had a
      complete neurological and biochemical response.

PMID- 16882083
TI  - Asthenospermia in hay fever patients improved by stopping treatment with
      histamine H1 receptor antagonists.
AB  - We report two cases of asthenospermia, which appeared to be associated with
      exposure to histamine H1 receptor antagonists. A 44-year-old man and a 35-year
      old man had continued the treatment with fexofenadine hydrochloride and
      cetirizine hydrochloride, respectively, under the diagnosis of hay fever. They
      and their wives had been examined as infertile couples. Infertility evaluations
      revealed no problems with their wives; the patients, however, were found to have
      a low sperm motility (<10%). On suspicion of adverse effects of the histamine H1
      receptor antagonists, they stopped treatment with these drugs, which resulted in
      a complete reversal of spermatic dysfunction. Current information identifies the
      potential fertility hazards of histamine H1 receptor antagonists.

PMID- 16882082
TI  - Advanced prostate cancer with extremely low prostate-specific antigen value at
      diagnosis: an example of high dose hook effect.
AB  - A 67-year-old man presented with a lower abdominal mass. Radiographic examination
      revealed a huge mass filling the entire pelvis. Although prostate-specific
      antigen (PSA) was 1.4 ng/ml, percutaneous needle biopsy revealed adenocarcinoma
      compatible with prostate cancer, which stained positive for PSA. Hormone therapy
      was initiated and 1 month later his PSA was as high as 2713 ng/ml, although the
      mass had decreased in size. High dose hook effect was suspected and hormone
      therapy was continued. PSA is presently under control and below 0.1 ng/ml. When
      prostate cancer with very high PSA is suspected and the PSA value is unexpectedly
      low hook effect should be considered and PSA should be re-analyzed.

PMID- 16882084
TI  - Pseudo-clitoromegaly associated with congenital prepubic sinus.
AB  - We operated on a 12-year-old girl who had clitoromegaly and a sinus on the
      midline prepubic area congenitally. The prepubic sinus appeared to point to the
      clitoris on the preoperative magnetic resonance image, but the relation between
      the sinus and clitoromegaly was unclear. Gray-brown discharge was emitted at the
      site of dissection between the prepuce and clitoris and the size of the clitoris
      became normal. The sinus was excised, revealing a tract 1.5 cm long that extended
      to the retropubic sinus, and ended in a fibrous tract that was linked to the
      clitoris. This suggested pseudo-hypertrophy because of the discharge collected in
      the end of the prepubic sinus.

PMID- 16882085
TI  - Testicular metastasis from hepatocellular carcinoma.
AB  - We document a case of testicular metastasis from hepatocellular carcinoma. The
      patient suffered from bilateral testicular painful swelling for 6 months. Scrotal
      ultrasonography showed bilateral testicular tumors and the whole abdominal
      computed tomography revealed a huge tumor in the left lobe of the liver.
      Bilateral orchiectomy and postoperative ultrasound-guided liver biopsy were done.
      Pathological examination revealed metastatic hepatocellular carcinoma.
      Hepatocellular carcinoma with testicular metastases is a very rare disease.

PMID- 16882086
TI  - Long-term survival under maintenance gemcitabine chemotherapy for metastatic
      transitional cell carcinoma.
AB  - We report a case of a 74-year-old patient who received 41 courses of maintenance
      therapy with gemcitabine over a length of 28 months for metastatic transitional
      cell carcinoma. One year earlier the patient had received three cycles of
      adjuvant cisplatin-based combination chemotherapy after nephro-ureterectomy for a
      locally advanced urothelial cancer of the right renal pelvis. This case
      demonstrates a paradigm shift in the palliative treatment of advanced urothelial
      cancer, with the implementation of more tolerable agents such as gemcitabine.
      Even elderly patients with impaired renal function may benefit in terms of tumor
      reduction and survival from systemic chemotherapy, which may be applied over a
      prolonged period of time.

PMID- 16882087
TI  - Seeing the genomic value of markers.

PMID- 16882089
TI  - Genetic evaluation of somatic cell score in dairy cattle considering first and
      later lactations as two different but correlated traits.
AB  - A test-day (TD) random regression model (RRM) was described for the genetic
      evaluation of somatic cell score (SCS) where first and later lactations were
      considered as two different but correlated traits. A two-step covariance function
      procedure was used to estimate variance-covariances and associated genetic
      parameters. Analysis of estimated breeding values (EBV), ranking of top bulls and
      cows and some computational aspects were used to compare RRM with TD
      repeatability model (RPM) and lactation average model (LAM). Residuals were
      analysed to assess the relative fit of TD models. Comparison between RRM and RPM
      showed that RRM has lower mean squared error and gave better fit to the data. For
      young bulls and cows, the standard deviation (SD) of EBVs was highest for RRM and
      lowest for LAM implying efficient utilization of information on SCS, in terms of
      revealing more genetic variation. A much lower correlation of EBVs ranging from
      0.80 to 0.92 and significant re-ranking of top bulls and cows were observed
      between RRM and LAM. The lower across-lactation correlation between RRM and LAM
      indicated that LAM is directed to give more weight to first lactation breeding
      values. The RRM, where SCS in the first and later lactations was considered as
      two different but correlated traits was able to make effective use of available
      information on young bulls and cows, and could offer an opportunity to breeders
      to utilize EBVs for first and later lactations.

PMID- 16882088
TI  - Strategy for applying genome-wide selection in dairy cattle.
AB  - Animals can be genotyped for thousands of single nucleotide polymorphisms (SNPs)
      at one time, where the SNPs are located at roughly 1-cM intervals throughout the
      genome. For each contiguous pair of SNPs there are four possible haplotypes that
      could be inherited from the sire. The effects of each interval on a trait can be
      estimated for all intervals simultaneously in a model where interval effects are
      random factors. Given the estimated effects of each haplotype for every interval
      in the genome, and given an animal's genotype, a 'genomic' estimated breeding
      value is obtained by summing the estimated effects for that genotype. The
      accuracy of that estimator of breeding values is around 80%. Because the genomic
      estimated breeding values can be calculated at birth, and because it has a high
      accuracy, a strategy that utilizes these advantages was compared with a
      traditional progeny testing strategy under a typical Canadian-like dairy cattle
      situation. Costs of proving bulls were reduced by 92% and genetic change was
      increased by a factor of 2. Genome-wide selection may become a popular tool for
      genetic improvement in livestock.

PMID- 16882090
TI  - The use of a random regression model to account for change in racing speed of
      German trotters with increasing age.
AB  - In a genetic analysis of German trotters, the performance trait racing time per
      km was analysed by using a random regression model on six different age classes
      (2-, 3-, 4-, 5- and 6-year-old and older trotters; the age class of 3-year-old
      trotters was additionally divided by birth months of horses into two seasons).
      The best-fitting random regression model for the trait racing time per km on six
      age classes included as fixed effects sex, race track, condition of race track
      (fitted as second-order polynomial on age), distance of race and each driver
      (fitted as first-order polynomial on age) as well as the year-season (fitted
      independent of age). The random additive genetic and permanent environmental
      effects were fitted as second-order polynomials on age. Data consisted of 138,620
      performance observations from 2,373 trotters and the pedigree data contained
      9,952 horses from a four-generation pedigree. Heritabilities for racing time per
      km increased from 0.01 to 0.18 at age classes from 2- to 4-year-old trotters,
      then slightly decreased for 5 year and substantially decreased for 6-year-old
      horses. Genetic correlations of racing time per km among the six age classes were
      very high (rg = 0.82-0.99). Heritability was h2 = 0.13 when using a repeatability
      animal model for racing time per km considering the six age classes as fixed
      effect. Breeding values using repeatability analysis over all and within age
      classes resulted in slightly different ranking of trotters than those using
      random regression analysis. When using random regression analysis almost no
      reranking of trotters over time took place. Generally, the analyses showed that
      using a random regression model improved the accuracy of selection of trotters
      over age classes.

PMID- 16882091
TI  - Evaluation of the efficiency of alternative two-tier nucleus breeding systems
      designed to improve meat sheep in Kenya.
AB  - A deterministic approach was used to genetically and economically evaluate the
      efficiency of five two-tier nucleus breeding systems for meat sheep in Kenya. The
      nucleus breeding systems differed in terms of whether the system was closed or
      open, in the type of animals that were involved in the movement of genetic
      superiority and in the number of selection pathways in each system. These systems
      were compared under four alternative breeding objectives based on monetary
      genetic gain and profit per ewe. The first objective simulated a situation where
      the flock size cannot be increased due to non-feed related constraints (FLOCK).
      The second specifically assumed that the flock size is restricted due to limited
      amount of feed resources (FEED). The third and fourth objectives assumed that
      sheep performed only tangible roles (TR) and both tangible and intangible roles
      (IR) in the production system respectively. Monetary genetic gains were highest
      for all objectives in an open nucleus system with a certain proportion of
      commercial-born ewes being introduced in the nucleus while at the same time
      utilizing young rams from the nucleus to breed sires and dams for the nucleus and
      commercial sector (ONyre). Utilizing young rams in a closed nucleus system for
      the dissemination of superior genes resulted in higher annual monetary genetic
      gain than utilization of old rams. Profit per ewe was significantly higher for
      FLOCK and IR in ONyre. In a closed system that allowed for downward movement of
      dams from the nucleus to the commercial sector to breed sires and dams, profit
      per ewe was highest for FEED and TR. The success of a nucleus breeding system
      should also focus on the profitability and logistics of establishing it. The
      implication of these results on the choice of two-tier nucleus breeding systems
      for the improvement of meat sheep is discussed.

PMID- 16882092
TI  - Microsatellite-based diversity analysis and genetic relationships of three Indian
      sheep breeds.
AB  - The genetic structure of three Indian sheep breeds from two different
      geographical locations (Nali, Chokla from north-western arid and semi-arid
      region; Garole from eastern saline marshy region) of India was investigated by
      means of 11 ovine-specific microsatellite markers as proposed in FAOs MoDAD
      programme. Microsatellite analysis revealed high allelic and gene diversity in
      all the three breeds. Nali sheep showed higher mean number of alleles and gene
      diversity (6.27 and 0.65) than Chokla (5.63 and 0.64) and Garole (5.63 and 0.59).
      High within population inbreeding estimates observed in the three breeds (FIS,
      Chokla = 0.286, Nali = 0.284, Garole = 0.227) reflected deficit of heterozygotes.
      The overall estimates for F-statistics were significantly (p < 0.05) different
      from zero. High values of FST (0.183) across all the loci revealed substantial
      degree of breed differentiation. Based on pair wise FST and Nm between different
      breeds, Nali and Chokla (FST = 6.62% and Nm = 4.80) were observed to be the
      closest followed by Garole and Nali (FST = 20.9% and Nm = 1.80), and Garole and
      Chokla (FST = 21.4% and Nm = 1.71). In addition, genetic distance estimates,
      phylogeny analysis and individual assignment test used to evaluate interbreed
      genetic proximity and population structure also revealed substantial genetic
      differentiation between Garole and the other two Rajasthani (Nali and Chokla)
      sheep. This divergent status of Garole sheep indicated genetic uniqueness of this
      breed suggesting higher priority for its conservation.

PMID- 16882093
TI  - Genetic characterisation and breed assignment in Austrian sheep breeds using
      microsatellite marker information.
AB  - Samples from 717 sheep of 11 Austrian sheep breeds were genotyped for 25
      microsatellite loci. Twenty-one loci showing no deviation from Hardy-Weinberg
      equilibrium were used to calculate pairwise genetic distances (Nei's minimum
      distance and Reynolds' distance). All breeds could be clearly distinguished
      through these genetic distances. The shortest genetic distance was found between
      Alpines Steinschaf (AS) and Waldschaf (WS). Within the so-called 'Steinschaf'
      group [AS, Montafoner Steinschaf (MS), Krainer Steinschaf (KS) and Tiroler
      Steinschaf (TS)] the MS adopted an extreme status with the largest distance to
      the other breeds in the group. This finding resulted in the decision to consider
      the MS no longer as subpopulation of Alpines Steinschaf but as an independent
      breed. A correct breed assignment using a Bayesian approach was possible for only
      66% of all individuals belonging to Alpines Steinschaf, but for at least 90% of
      individuals for all other breeds investigated.

PMID- 16882094
TI  - Response to intensity of reproduction in mouse lines resistant or susceptible to
      fescue toxicosis.
AB  - Our objective was to examine whether mouse lines divergently selected for
      response to fescue toxicosis differed in the impact of increasing reproductive
      intensity on growth, final weight or first and second parity reproduction.
      Resistant (R) and susceptible (S) females were never mated (NR), mated only once
      (low reproduction, LR), mated after their first litter was weaned (moderate
      reproduction, MR) or paired continuously with a male (high reproduction, HR),
      allowing concurrent pregnancy and lactation. Final weight was significantly
      higher in mated than in not mated females (31.6 +/- 0.6, 35.9 +/- 0.6, 36.8 +/-
      0.6 and 37.2 +/- 0.5 g for NR, LR, MR and HR females respectively), but the
      effect of increasing reproductive intensity was similar in both lines. Neither
      genetic line, reproductive treatment (LR and MR versus HR) nor their interaction
      affected first parity traits of dams or pups. In second parity, S dams produced
      larger litters at birth and weaning and heavier litters at birth than R dams, and
      MR dams produced more pups and heavier litters than HR dams. As with first
      litters, however, line by reproductive treatment interactions were not
      significant or important. Concurrent pregnancy and lactation (the HR treatment)
      had a similar dampening impact on the expected increase in litter size between
      first and second parity of both lines. Thus, lines divergently selected for
      toxicosis response did not differ significantly in the impact of increasing
      reproductive intensity on dam or pup growth, reproductive output through two
      parities or mature size. This conclusion should not be generalized. Selection
      responses in livestock should be monitored to ensure that improvement in one
      trait does not lead to deterioration in others.

PMID- 16882095
TI  - SNP identification, linkage and radiation hybrid mapping of the porcine lamin A/C
      (LMNA) gene to chromosome 4q.
AB  - The lamins are components of nuclear lamina and they have a profound influence on
      nuclear structure and functions. They are encoded by three genes, LMNA, LMNB1 and
      LMNB2. A genomic fragment of the porcine LMNA gene (822 bp; from exons 7 to 9)
      was amplified by polymerase chain reaction and comparatively sequenced. Four
      single nucleotide polymorphisms (SNPs) were identified in intronic sequences:
      G162A, G208A, T367G and C618T. The SNPs are within the restriction sites for
      enzymes Bsh1236I, HpaII, AluI and Bsh1236I respectively. Allele frequencies at
      SNPs G208A, T367G and C618T were determined by using eight pig breeds. Linkage
      analysis in the Hohenheim Meishan x Pietrain family placed the LMNA gene in the
      chromosome 4q linkage group, between MEF2D and GBA (MEF2D - 3.0 cM - LMNA - 0.2
      cM - GBA). In radiation hybrid mapping LMNA was most significantly linked to
      SW270 on chromosome 4 (39 cR; LOD = 7.86). The LMNA gene is located in the
      quantitative trait loci region for some carcass traits on chromosome 4q.

PMID- 16882096
TI  - Polymorphism and chromosomal localization of the porcine signal transducer and
      activator of transcription 5B gene (STAT5B).
AB  - Signal transducers and activators of transcription (STATs) are a family of
      transcription factors. STAT5A and 5B are two highly related proteins encoded by
      two distinct genes. Transgenic knockout mice studies have indicated the
      importance of STAT5 proteins for the regulation of both lactation and growth
      performance. Moreover, different studies determine the role of STAT5 proteins in
      the modulation of adipocyte function. In this study, we sequenced one fragment of
      STAT5B gene from animals of six breeds (Duroc, Iberian, Landrace, Large White,
      Pietrain and Meishan) to identify genetic variants. A G/A single nucleotide
      polymorphism in intron 14 creates a polymorphic PstI restriction site and was
      genotyped by polymerase chain reaction restriction fragment length polymorphism
      in the six breeds. Allele G was only present in Large White, Pietrain and Meishan
      populations, detecting only G allele in this last pig breed. The STAT5B gene was
      located by radiation hybrid mapping to porcine chromosome 12, within the
      confidence interval for the fatty acid composition quantitative trait loci,
      previously identified in an Iberian x Landrace cross.

PMID- 16882098
TI  - The Anglo-Scandinavian Cardiac Outcomes Trial-- blood pressure lowering arm.

PMID- 16882099
TI  - Efficacy and safety of over-the-counter analgesics in the treatment of common
      cold and flu.
AB  - RATIONALE: Common cold and flu are the most common human illnesses, and over-the
      counter (OTC) analgesics are widely used to treat the pain and fever symptoms.
      Despite the every day use of these analgesic there is little information
      available in the literature on the efficacy and safety of these medicines in
      treating colds and flu symptoms. The aim of this review was to determine the
      safety and efficacy of the analgesics, aspirin, paracetamol and aspirin for the
      treatment of colds and flu. METHODS: Electronic databases and a personal database
      were searched and the information retrieved together with information from
      relevant textbooks has been integrated in the review. RESULTS: The literature
      search established that there is relatively little information on the use of
      analgesics in treating colds and flu and that much of the safety and efficacy
      data must be related to other pain and fever models. The review establishes that
      aspirin, paracetamol and ibuprofen are safe in OTC doses and that there is no
      evidence for any difference between the medicines as regards efficacy and safety
      for treatment of colds and flu (except in certain cases such as the use of
      aspirin in feverish children). There is also no evidence that these medicines
      prolong the course of colds and flu by any effect on the immune system or by
      reducing fever. CONCLUSION: Despite the lack of clinical data on the safety and
      efficacy of analgesics for the treatment of colds and flu symptoms a case can be
      made that these medicines are safe and effective for treatment of these common
      illnesses.

PMID- 16882100
TI  - Effect of delayed and/or missed enteric-coated divalproex doses on valproic acid
      concentrations: simulation and dose replacement recommendations for the
      clinician.
AB  - BACKGROUND AND OBJECTIVE: Enteric-coated, delayed-release divalproex sodium
      requires multiple daily administrations and high adherence rate to prevent
      breakthrough seizures and control adverse effects. We evaluated the effect of
      missing one or two doses of divalproex for up to 24 h, followed by replacement
      and resumption of scheduled therapy, on plasma valproic acid (VPA)
      concentrations. METHODS: Comprehensive simulations using well-established VPA
      pharmacokinetic parameters were performed for two distinct populations on every
      12-h divalproex therapy: monotherapy patients and polytherapy patients on hepatic
      enzyme-inducing antiepileptics. RESULTS: In polytherapy patients on c. 32.1
      mg/kg/day, steady-state (no missed doses) mean VPA minimum (C(min)) and maximum
      (C(max)) concentrations were 67 and 98 mg/L, respectively. When dose(s) were
      missed for 12, 18 and 24 h, mean C(min) fell to 37, 28 and 20 mg/L, respectively,
      below the threshold 50 mg/L VPA concentration generally required to maintain
      efficacy. Replacing, then resuming the next regularly scheduled divalproex dose
      increased mean C(max) to 113, 117 and 129 mg/L upon replacement at 12, 18 and 24
      h, respectively; a mean increment of 31 mg/L for replacement at 24 h. Less
      pronounced changes in VPA concentrations occurred in monotherapy patients (enzyme
      uninduced) on approximately 16.1 mg/kg/day. CONCLUSIONS: These simulations
      predict that the risk of high VPA concentrations which may lead to clinical
      toxicity is low for patients not concurrently taking enzyme-inducing
      antiepileptic drugs (uninduced), even when divalproex doses are replaced at 24
      h(effectively tripling the dose at that time). However, the same action in
      induced patients may result in drug levels leading to transient clinical
      toxicity; the optimal regimen for replacing a missed enteric-coated divalproex
      dose beyond 12 h remains to be determined.

PMID- 16882101
TI  - Effects of sun ginseng on subjective quality of life in cancer patients: a double
      blind, placebo-controlled pilot trial.
AB  - OBJECTIVE: Ginseng has been reported to increase mental and physical abilities,
      improve mood and promote general health and well-being. The purpose of this study
      was to examine the effects of sun ginseng (SG) on quality of life in cancer
      patients. METHODS: A randomized, double-blind, placebo-controlled pilot trial was
      performed for 12 weeks. Fifty-three patients were randomly assigned to SG 3000 mg
      a day (n = 32) or placebo (n = 21) in a 3 : 2 ratio. Patients' diagnoses were
      gynecologic cancer (n = 28), hepatobiliary cancer (n = 13) and other cancers (n =
      12). Quality of life was assessed using the World Health Organization Quality of
      Life Assessment-Bref (WHOQOL-BREF) and the General Health Questionnaire-12 (GHQ
      12). RESULTS: After 12 weeks of therapy, the 'psychological domain' score of the
      WHOQOL-BREF was significantly improved in patients randomized to SG, compared
      with those randomized to placebo (P = 0.02). There was a tendency for SG to
      improve the 'physical health' (P = 0.06) and 'environment' (P = 0.07) domain
      scores of the WHOQOL-BREF, compared with placebo. The GHQ-12 total score was
      significantly improved in patients treated with SG than in those with placebo (P
      < 0.01). No significant adverse events were observed in both groups of patients.
      CONCLUSIONS: Sun ginseng was found to be beneficial in improving some aspects of
      mental and physical functioning after 12 weeks of therapy in cancer patients, who
      were mainly diagnosed with gynaecologic cancer or hepatobiliary cancer. Further
      studies are required to evaluate the long-term effects of SG on multiple facets
      of quality of life in various cancer patients.

PMID- 16882102
TI  - Adverse drug reactions in hospital in-patients: a pilot study.
AB  - BACKGROUND: About 6.5% of admissions to hospital are related to an adverse drug
      reaction (ADR). There are no recent large studies, which explore the burden of
      ADRs on hospital in-patients. The aim of this pilot study was to assess the
      feasibility of, and establish the methodology for, conducting a large prospective
      study to fully assess the impact of ADRs on in-patients and the National Health
      Service (NHS). METHODS: Patients admitted to five wards in a university hospital
      over a 2-week period were assessed for ADRs through a daily ward visit by a
      pharmacist. Suspected ADRs were analysed for causality, severity and avoidability
      using appropriate scales. RESULTS: Twenty-four of 125 patients (19.2%, 95% CI 12
      26%) were categorized as having suffered one or more ADRs. A total of 27 ADRs
      were identified. Patients with ADRs spent longer in hospital than those without
      ADRs. Causality assessment showed that 17 (63%) ADRs were possibly drug-related,
      whereas 10 (37%) were classified as probably or definitely related to the drug.
      Almost two-thirds of reactions were potentially avoidable. Intervention was
      required in all ADRs and reactions indirectly contributed to the death of two
      patients. CONCLUSIONS: Almost one-fifth of patients suffered an ADR as an
      inpatient. Methodology tested using this pilot will enable the design of a larger
      study, involving over 3000 patients, which will allow the ADR burden and
      vulnerable patient groups, to be more accurately characterized. This study will
      aid the development of interventions to reduce the impact of ADRs in hospital in
      patients.

PMID- 16882103
TI  - The effect of various methods of psoriasis treatment on somatotrophin axis
      hormones in serum.
AB  - OBJECTIVE: To investigate the effect of pharmacotherapy and phototherapy on the
      concentration of hormones of the somatotrophin axis [growth hormone (GH), insulin
      like growth factor-I (IGF-I) and insulin-like growth factor binding protein-3
      (IGFBP-3)] in the serum of patients with psoriasis in exacerbation and remission.
      METHODS: GH and IGFBP-3 in serum were determined by immunoradiometric assay
      (IRMA), and IGF-I concentrations - by radioimmunological assay (RIA). The
      dermatological state was assessed by the psoriasis area and severity index
      (PASI). RESULTS: There was no significant difference in the GH concentrations in
      patients both in exacerbation and remission, irrespective of therapy applied.
      However, in the group treated by phototherapy a significant increase in IGFBP-3
      secretion was observed, whereas in the group treated with cyclosporin A - a
      significant increase in IGF-I secretion was observed in remission. CONCLUSION:
      Different methods of treatment have different effects on the secretion of
      somatotrophin axis hormones, but generally the hormone concentrations do not
      return to the values observed in healthy people. The therapeutic actions of the
      drugs concerned are not fully known and require further investigations.

PMID- 16882105
TI  - Benchmarking the current dispensing rate of Welsh hospital pharmacies.
AB  - BACKGROUND: There is a need to develop capacity measures for pharmacy services
      for strategic purposes, to provide guidance on safe working limits and to
      contribute to the target 40% reduction in serious medication errors by 2005.
      Attempts have been made to quantify workloads in the form of items/person/hour
      (i/p/h). However, much of these data are anecdotal, small scale or associated
      with vague methodology. OBJECTIVE: We estimate national average dispensing rates
      by collecting accurate data from secondary care dispensaries across Wales.
      METHOD: Seventeen sites collected hourly data relating to staff time and items
      dispensed over a 3-day period. The result showed a Welsh national average for non
      specialist hospital pharmacy dispensing rates of 9.9 items/person/h (95% CI =
      0.9, n = 17). There was a significant positive association between hospital size
      and telephone interruptions (r(s) = 0.83, P < 0.001) but no correlation between
      hospital size and dispensing rates (r(s) = 0.06, P = 0.822).

PMID- 16882104
TI  - Calcitonin gene-related peptide and somatostatin releases correlated with the
      area under the lafutidine concentration-time curve in human plasma.
AB  - OBJECTIVE: To examine the effects of the histamine H(2)-receptor antagonist,
      lafutidine, at clinical dosage (10 mg tablet after a standardized meal) on plasma
      levels of the gastrointestinal peptides, calcitonin gene-related peptide (CGRP),
      somatostatin and gastrin. METHODS: Six healthy male volunteers ate a standardized
      meal, and received either lafutidine orally at a dose of 10 mg or water only
      (control). Blood samples were taken before and up to 4 h after the drug
      administration. Plasma lafutidine concentrations were determined by high pressure
      liquid chromatography. Pharmacokinetic analysis of lafutidine was performed using
      one-compartmental model. The levels of immunoreactive substances of plasma CGRP,
      somatostatin and gastrin were measured by enzyme immunoassay, and the amount of
      peptide release was calculated by the trapezoidal method. Lafutidine
      significantly increased plasma CGRP levels at 1, 1.5, 2.5 and 4 h and the total
      amount of CGRP release (192 +/- 14.0 pg.h/mL) compared with the control group
      (128 +/- 21.5 pg.h/mL). RESULTS: Lafutidine significantly increased the plasma
      somatostatin levels at 1 and 1.5 h, and the total amount of somatostatin released
      (107 +/- 18.2 pg.h/mL) compared with the control (78.4 +/- 7.70 pg.h/mL). The
      area under the drug concentration-time curve (AUC) from 0 to 4 h after
      administration correlated well with the Delta-CGRP and Delta-somatostatin release
      but not with total amount of gastrin released. However, plasma gastrin levels
      were significantly elevated at 1.5 h after drug administration. CONCLUSION:
      Lafutidine at clinical dosage increases plasma CGRP and the somatostatin. The
      amounts released correlated with the AUC of lafutidine in humans. These results
      suggest that the increased release of CGRP and somatostatin may contribute to its
      gastroprotective and anti-acid secretory effect.

PMID- 16882106
TI  - Alveolar-capillary membrane permeability for early prediction of response of
      inhaled steroid on patients with chronic obstructive pulmonary disease.
AB  - BACKGROUND AND OBJECTIVE: Glucocorticosteroid reversibility-testing is undertaken
      over a period of 3 months to identify whether patients with chronic obstructive
      pulmonary disease (COPD) would benefit from long-term inhaled corticosteroids.
      This study assessed whether alveolar-capillary membrane (a/c) permeability
      testing can be used as an early alternative test method for the same purpose.
      METHODS: Fourteen patients with severe and symptomatic moderate COPD (group S)
      were prescribed inhaled steroid 800 microg/day for 3 months. Before inhalation
      and 4 weeks after inhalation therapy, forced expiratory volume in 1 s (FEV(1))
      and a/c permeability using (99m)Tc-DTPA were performed. FEV(1) was recorded again
      at the end of the third month. Another 10 patients with COPD of comparable
      severity (group B) prescribed with inhaled bronchodilators were examined and
      studied as controls. RESULTS: In group S, the permeability decreased in eight
      patients (group D) and increased in six patients (group I). No significant change
      was noted in FEV(1) at the end of the first month. However, seven patients in
      group D showed significant improvement in FEV(1) at the end of the third month,
      whereas in patients in group I no significant changes were observed. In group B,
      no significant change in a/c permeability was observed, although the FEV(1)
      increased by 12-17%. CONCLUSION: With steroid inhalation, the a/c permeability at
      4 weeks predicts future changes in lung functions. Long-term inhaled
      corticosteroids are likely to be useful if permeability decreases. This test,
      which needs further validation, appears to provide much earlier prediction of
      response than glucocorticoid reversibility testing.

PMID- 16882107
TI  - Pharmacotherapeutic management of COPD patients in Greece--adherence to
      international guidelines.
AB  - BACKGROUND: International guidelines for Chronic Obstructive Pulmonary Disease
      (COPD) propose the most cost-effective management of the disease. However, the
      management of COPD differs between countries and between clinics within the same
      country. OBJECTIVE: To examine prescription trends for COPD by Lung Specialists
      (LS) and Primary Care Physicians (PCP) in Greece and to study prescription
      adherence to international guidelines. METHODS: A retrospective analysis of COPD
      prescriptions, obtained from pharmacies located all over the country, was
      performed between 1997 and the beginning of 2003. The data collected were
      compared with those of other European countries. A subgroup analysis was carried
      out for prescriptions issued by PCP and LS. RESULTS: Between 1997 and 2003, LS
      and PCP used different pharmacological interventions for the management of COPD.
      Only the LS prescriptions showed a tendency to guideline adherence. Differences
      in preferences for different pharmacological drug classes were noted. Thus, LSs
      were found to generally prefer inhaled corticosteroids (ICSs), followed by
      anticholinergic drug + a beta(2)-short-acting agonist combinations, long-acting
      beta(2)-agonists, xanthines, short-acting beta(2)-agonists and expectorants. In
      contrast, PCPs used mostly short-acting beta(2)-agonists followed by xanthines,
      ICSs, expectorants, anticholinergic drug + beta(2)-short-acting agonist
      combinations and long-acting beta(2)-agonists. CONCLUSIONS: It appears that
      compliance to international COPD management-guidelines in force at the time of
      the study increased between 1997 and 2003 only for LSs but not for PCPs.

PMID- 16882109
TI  - Allergic contact angioedema to benzoyl peroxide.
AB  - Benzoyl peroxide (BP) is commonly used for topical acne treatment and has long
      been known to be a weak allergen and a strong irritant. We report a case of a 26
      year-old woman, who presented with an itchy erythematous reaction and strong
      oedema localized to the face. Two weeks before angioedema, the patient had
      started a new topical treatment with a gel containing 10% BP for acne. She was
      patch tested to European Standard Series, including BP 1% in white petrolatum,
      and to the 10% BP-containing gel previously used by herself, showing positivity
      on day 2 to BP 1% and to the 10% BP-containing gel. Factors that suggested an
      association between the severe angioedematous reaction and BP topical application
      include the strong reaction to BP in the patch-test, the temporal relationship,
      the complete resolution of symptoms after the drug was withdrawn and the absence
      of other identified explanations.

PMID- 16882108
TI  - Metformin-pioglitazone and metformin-rosiglitazone effects on non-conventional
      cardiovascular risk factors plasma level in type 2 diabetic patients with
      metabolic syndrome.
AB  - BACKGROUND AND OBJECTIVE: Metformin is considered the gold standard for type 2
      diabetes treatment as monotherapy and in combination with sulphonylureas and
      insulin. The combination of metformin with thiazolidinediones is less well
      studied. The aim of the present study was to assess the differential effect, and
      tolerability, of metformin combined with pioglitazone or rosiglitazone on
      glucose, coagulation and fibrinolysis parameters in patients with type 2 diabetes
      mellitus and metabolic syndrome. METHODS: This 12-month, multicentre, double
      blind, randomized, controlled, parallel-group trial was conducted at three study
      sites in Italy. We assessed patients with type 2 diabetes mellitus (duration
      >or=6 months) and with metabolic syndrome. All patients were required to have
      poor glycaemic control with diet, or experienced adverse effects with diet and
      metformin, administered up to the maximum tolerated dose. Patients were
      randomized to receive either pioglitazone or rosiglitazone self-administered for
      12 months. We assessed body mass index (BMI), glycaemic control [glycosylated
      haemoglobin (HbA(1c)), fasting and postprandial plasma glucose and insulin levels
      (FPG, PPG, FPI, and PPI respectively), homeostasis model assessment (HOMA)
      index], lipid profile [total cholesterol (TC), low-density lipoprotein
      cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C) and
      triglycerides (TG)], lipoprotein (a) [Lp(a)] and homocysteine (HCT) at baseline
      and at 3, 6, 9 and 12 months of treatment. RESULTS AND DISCUSSION: No BMI change
      was observed at 3, 6, 9 and 12 months in either group. Significant HbA(1c)
      decreases were observed at 9 and 12 months in both groups. After 9 and 12 months,
      mean FPG and PPG levels decreased in both groups. Decreases in FPI and PPI were
      observed at 9 and 12 months compared with the baseline in both groups.
      Furthermore, in both groups, the HOMA index improved but only at 12 months.
      Significant TC, LDL-C, HDL-C, TG improvement was present in the pioglitazone
      group at 12 months compared with the baseline values, and these variations were
      significantly different between groups. No TC, LDL-C, TG improvement was present
      in the rosiglitazone group after 12 months. Significant Lp(a) and HCT improvement
      was present in the pioglitazone group at 12 months compared with the baseline
      values, and Lp(a) change was significant compared with the rosiglitazone group.
      Significant HCT decrease was observed in the rosiglitazone group at the end of
      the study. In our type 2 diabetic patients, both drugs were safe and effective
      for glycaemic control and improving HCT plasma levels. However, long-term
      treatment with metformin plus pioglitazone significantly reduced Lp(a) plasma
      levels, whereas metformin + rosiglitazone did not. CONCLUSION: For patients with
      type 2 diabetes mellitus and metabolic syndrome, combined treatment with
      metformin and rosiglitazone or pioglitazone is safe and effective, However, the
      pioglitazone combination also reduced the plasma Lp(a) levels whereas the
      rosiglitazone combination did not.

PMID- 16882110
TI  - Gemtuzumab ozogamicin-induced sinusoidal obstructive syndrome treated with
      defibrotide: a case report.
AB  - New treatments for relapse of acute myeloid leukaemia (AML), include gemtuzumab
      ozogamicin (GO), an anti-CD33 monoclonal antibody. We describe a second case of
      GO-induced sinusoidal obstructive syndrome (SOS) effectively treated with
      defibrotide (DF). No stem-cell transplantation was involved. On day 23 after the
      first GO dose, a patient presented with ascites, weight gain, liver enlargement
      and pain in the right upper quadrant. Sudden hepatic cytolysis (transaminases at
      six times the normal range: grade 3) and cholestasis [alkaline phosphatase ALP
      and gamma-glutamyltransferase (GGT) respectively at four and eight times the
      normal range: grade 2] were observed but there was no evidence of increase serum
      bilirubin. Treatment with DF (Prociclide), Crinos; 10 mg/kg/day, or 200 mg,
      q.i.d.) improved the hepatic abnormality within a few days (serum transaminases
      decreased from 312 to 103 IU/L for aspartate aminotransferase (AST) and from 141
      to 80 IU/L for alanine aminotransferase (ALT) within 3 days ALP increased from
      253 to 383 IU/L and gamma-GT from 238 to 417 IU/L 4 days after administration of
      DF. The clinical and biological features of our case suggest a direct involvement
      of GO in causing SOS, even when used as monotherapy, without allogenic stem-cell
      transplantation. Low dose DF (10 mg/kg/day) given early during the development of
      SOS associated with GO was effective. Unfortunately, in our case the patient
      eventually died of multi-organ failure probably because of failure of GO.

PMID- 16882111
TI  - Epileptic seizures caused by low valproic acid levels from an interaction with
      meropenem.
AB  - A 55-year-old woman was diagnosed with pneumonia and was treated with meropenem;
      5 days later she developed epileptic seizures. She had been treated with valproic
      acid for 16 years to control her epileptic seizures. Her serum valproic acid
      concentration was low during treatment with meropenem than previously recorded
      despite an increase of valproic dose. As soon as administration of meropenem was
      withdrawn, valproic acid concentration increased to previous levels and her
      seizures stopped. Meropenem decreases valproic acid concentration, and may
      promote the development of epileptic seizures in previously controlled epileptic
      patients. The acute lowering of serum valproate produced by meropenem probably
      precludes their concomitant use.

PMID- 16882112
TI  - Lithium and venlafaxine interaction: a case of serotonin syndrome.
AB  - Serotonin syndrome, which occurs as a result of enhanced serotonin concentration
      in the central nervous system, is a well-known adverse effect of serotonin-active
      medications. The concomitant use of antidepressant drugs associated with lithium
      as a co-adjuvant seems to increase the risk of this adverse reaction. We report a
      case of the serotonin syndrome during treatment with lithium and venlafaxine, an
      antidepressant with a dual selective re-uptake inhibition mechanism, and review
      the literature for similar cases. A 71-year-old woman developed serotonin
      syndrome while receiving treatment with moderate doses of lithium and venlafaxine
      for refractory depression. She had been taking higher doses of venlafaxine during
      the previous months with no significant secondary effects. Use of the Naranjo
      adverse drug reaction probability algorithm indicated a probable relationship
      between serotonin syndrome and treatment with lithium and venlafaxine.

PMID- 16882113
TI  - Chronic myelomonocytic leukaemia after platinum-based therapy for non-small cell
      lung cancer: case report and review of the literature.
AB  - Chronic myelomonocytic leukaemia (CMML) is a preleukaemic condition with
      myeloproliferative features, and classified as a part of myelodysplastic syndrome
      (MDS). Other than alkylating agents and topoisomerase II inhibitors, there is
      less evidence that chemotherapeutic drugs are associated with therapy-related
      CMML, acute leukaemia or MDS. We present a patient who developed CMML within 2
      years of platinum-based chemotherapy for a metastatic non-small cell lung cancer.
      He received a cumulative dose of 240 mg/m(2) of cisplatin, and 1123 mg/m(2) of
      carboplatin before developing CMML. The cytogenetic study revealed trisomy 8.
      This is the first reported case that links platinum-based therapy with
      development of CMML with trisomy 8. Although the relationship between platinum
      therapy and the development of CMML is difficult to assess due to combinational
      nature of therapy in most cases, physicians should consider the possibility of
      CMML in patients with symptoms or signs suggestive of haematologic malignancy
      after platinum therapy.

PMID- 16882114
TI  - Correspondence to 'dose evaluation for long-term magnesium treatment in
      aneurysmal subarachnoid haemorrhage'.

PMID- 16882116
TI  - Patients with head and neck cancer prefer individualized cognitive behavioural
      therapy.
AB  - Cognitive behaviour therapy (CBT) is a widely practiced and approved form of
      psychotherapy for many psychosocial difficulties. As the efficacy of CBT is
      recognized, its demand has increased and today exceeds the availability of
      qualified practitioners. Therefore, the effectiveness of delivering CBT using
      less labour-intensive modes than individualised therapy has been explored. These
      include group therapy, bibliotherapy and computer assisted therapy. Given the UK
      Government's impetus towards patient choice and involvement in the planning of
      healthcare, it was thought essential to ascertain the preferred delivery mode of
      patients with head and neck cancer for a CBT based intervention. Therefore, a
      small retrospective cohort (n= 28) of patients following treatment for head and
      neck cancer were sent postal questionnaires to ascertain their preferences on
      mode of CBT delivery. Simultaneously, the views of accredited cognitive behaviour
      therapists (n= 14) were determined on the optimal mode of CBT delivery to these
      patients. Findings indicated that patients preferred the more individualized mode
      of CBT delivery, namely one-to-one therapy, followed closely by bibliotherapy,
      with group format being the least preferred option. Professionals concurred with
      patients, in that one-to-one interaction was considered an optimal mode of CBT
      delivery, but professionals considered it equal to group therapy.

PMID- 16882117
TI  - A scoring system for the assessment of oral mucositis in daily nursing practice.
AB  - Nurses take care of patients around the clock, so they are in an ideal position
      to observe and record the signs and symptoms of oral mucositis. This requires a
      valid, reliable scoring instrument that is easy to use. The objectives of this
      study were to summarize the scoring instruments that are available, to develop a
      new Nijmegen Nursing Mucositis Scoring System (NNMSS) and to evaluate this new
      instrument. A systematic review was undertaken in which 21 scoring instruments
      were reviewed and compared. None of the instruments studied satisfied the
      criteria that were established beforehand. The six most common items from the
      systematic review were selected for the new instrument. To test the NNMSS, pairs
      of experienced nurses assessed the oral cavity of 26 patients independently.
      Inter-observer reliability (Kappa), correlation between items (Spearman's rank
      order correlations) and internal consistency of the instrument (Cronbach's alpha)
      were calculated. The usability was evaluated with a questionnaire. Cohen's
      weighted Kappa was within an acceptable range. Almost all correlations were
      statistically significant and in the predicted direction. The Cronbach's alpha
      coefficient indicated sufficient internal consistency. All nurses found the NNMSS
      user-friendly and suitable for day-to-day care. The NNMSS can be used as a valid,
      reliable and usable instrument in daily nursing practice.

PMID- 16882118
TI  - Refill adherence to repeat prescriptions of cancer drugs to ambulatory patients.
AB  - The objective was to study the refill adherence among ambulatory patients with
      prescribed cancer drugs. The study was based on copies of repeat prescriptions,
      which were collected at three large Swedish pharmacies during the last 3 months
      of 2004. Copies of 141 repeat prescriptions were analysed. There was no
      statistical significant difference between the number of patients with
      undersupply of cancer drugs (i.e. <80% of prescribed cancer drugs) and that of
      patients with undersupply of all other drugs, or between the number of patients
      with oversupply of cancer drugs (>120% of prescribed cancer drugs) and that of
      patients with oversupply of all other drugs. Undersupply of drugs was found among
      14% of the patients. The median treatment gap for these patients was 39 (range 29
      49 days) per 98-100 days of prescribed treatment time, meaning that the
      undersupply leads to treatment gaps that may jeopardize their therapeutic
      outcome. It is reasonable to expect that more seriously ill patients would be
      adherent to prescribed medication, and consequently that cancer patients would
      have high adherence. However, our data show that cancer patients on oral long
      term treatment have a non-adherence similar to that of patients in general.

PMID- 16882119
TI  - A clinical interview assessing cancer patients' spiritual needs and preferences.
AB  - We conducted a phase-I study to test the practicability and usefulness of a short
      (15-30 min) clinical interview for the assessment of cancer patients' spiritual
      needs and preferences. Physicians assessed the spirituality of their patients
      using the semi-structured interview SPIR. The interview focuses on the meaning
      and effect of spirituality in the patient's life and coping system. Visual
      Analogue Scales (VAS) and Questionnaires were completed following the interview
      for rating whether SPIR had been helpful or distressing, and to what extent
      spirituality seemed important in the patient's life and in coping with cancer
      disease. Thirty oncological outpatients who all agreed to participate were
      included. The majority wanted their doctor to be interested in their spiritual
      orientation. Patients and interviewing physicians evaluated the SPIR interview as
      helpful (patients mean 6.76 +/- 2.5, physicians 7.31 +/- 1.9, scale from 0 to 10)
      and non-distressing (patients 1.29 +/- 2.5, physicians 1.15 +/- 1.3, scale from 0
      to 10). Following the interview, doctors were able to correctly gauge the
      importance of spirituality for their patients. Patients who considered the
      interview as very helpful (VAS > 7) were more often female (P = 0.002). There
      were no differences between patients who evaluated the SPIR as very helpful and
      those who did not, as far as diagnosis, educational level or belonging to a
      religious community were concerned. The present study shows that a short clinical
      assessment of cancer patients' spirituality is well received by both patients and
      physicians. The SPIR interview may be a helpful tool for addressing the spiritual
      domain, planning referrals and ultimately strengthening the patient-physician
      relationship.

PMID- 16882120
TI  - A qualitative study of anterior resection syndrome: the experiences of cancer
      survivors who have undergone resection surgery.
AB  - This study aimed to explore how individuals recovered and adapted following
      surgical resection of their rectal cancer and the syndrome that occurs as a
      consequence of this operation. This syndrome, 'anterior resection syndrome',
      consists of frequency, urgency, fragmentation and incontinence of faeces, and is
      thought to occur in 90% of patients who have received this type of surgery.
      Little qualitative research has been undertaken in this area, and this study adds
      to current quality of life data and explores supportive care strategies that
      nurses could use to assist patients. This study uses a grounded theory approach
      and in-depth interviews to explore patient's experiences. Participants were
      recruited from a cancer unit within the UK. Participants were recruited from a
      total population sample of 27 patients who had received surgery from 2001 to
      2002. Following eligibility criteria to exclude those who had disease
      progression, seven patients were identified 1 year following surgery. Interviews
      were used to explore the experience of the syndrome. Three categories were
      identified: adapting to the physical changes, psychological adaptation and
      stigma. A secondary theme, running throughout all these categories, was the
      feeling of confidence and normality. Although the physical changes were expected
      as a consequence of surgery, most participants described the difficulty in
      controlling and managing symptoms in their period of recovery. Developing a
      philosophical stance was important in managing the lack of control and returning
      to perceived normality, despite the social stigma of bowel problems. Information
      on a range of strategies to manage physical symptoms is helpful in providing
      supportive care. Understanding that patients often rely on inappropriate
      strategies for management and are reluctant to discuss symptoms is important. The
      specialist nurse has a role in providing supportive care in managing chronic
      symptoms following cancer treatment.

PMID- 16882122
TI  - When legal worlds collide: from research to treatment in hereditary cancer
      prevention.
AB  - This paper critically examines the legal and ethical dilemma in the
      institutionalization of a prevention and treatment technology on hereditary non
      polyposis colorectal cancer (HNPCC) in Finland. Current medical practice and
      legislation support the notion of non-directiveness in genetic counselling,
      patient autonomy and personal privacy. Clinical doctors in Finland, however,
      proposed that a research register of HNPCC carriers should be nationalized
      through a legal mandate, which would require all carriers to be identified on the
      basis of the mutation, but also provide a national healthcare and counselling
      infrastructure for preventive treatment. This paper argues that although such a
      register would undermine personal autonomy and privacy, there should be a strong
      incentive by the state to intervene from a preventive health perspective. Such a
      position would be contrary to current medical ethics and legal practice, but it
      would ensure that all patients receive equal access to information, screening and
      treatment, as well as help to reduce mortality rates.

PMID- 16882121
TI  - Influence of cardiopulmonary resuscitation on levels of tumour markers.
AB  - Tumour markers (TM), including alpha-fetoprotein (AFP), carcinoembryonic antigen
      (CEA), cancer antigen (CA) 15-3 and prostate-specific antigen (PSA), are serum
      markers for malignant diseases. Previous studies investigating the effect of
      acute and chronic inflammation, cardiopulmonary bypass surgery and
      cardiopulmonary resuscitation (CPR) on levels of TM showed conflicting results.
      Cardiopulmonary resuscitation (CPR) may result in a profound inflammatory
      response, and is frequently associated with severe tissue hypoperfusion. The
      present study investigated whether AFP, CEA, CA 15-3 and PSA are influenced by
      CPR. Alpha-fetoprotein (AFP), CEA, CA 15-3 and PSA (only in male patients) were
      assessed immediately after hospital admission, 6 h, 12 h and 2 days after
      prolonged CPR in eight male and 12 female patients. Serum levels of AFP, CEA, CA
      15-3 did not change significantly after CPR. Prostate-specific antigen (PSA)
      levels increased significantly with a highest level in the study period 48 h
      after CPR (3.3 +/- 3.1 and 28.3 +/- 30.5 ng/mL for baseline and 48 h levels,
      respectively; P < 0.001). Alpha-fetoprotein (AFP), CEA, CA 15-3 and PSA (in men)
      values above the normal range were observed in 0%, 13.8%, 3.8% and 46.9% of all
      measurements respectively. At least one value above the normal range were
      observed in 0%, 20%, 5% and 75% of all patients for AFP, CEA, CA 15-3 and PSA (in
      men) respectively. Baseline values of AFP, CEA, CA 15-3 and PSA (in men) were
      above the normal range in 0%, 15%, 5% and 10% of all patients respectively.
      Levels for all markers did not differ significantly between survivors and non
      survivors. In conclusion, prolonged CPR does not influence AFP, CEA, CA 15-3
      serum levels, but is frequently associated with increases of PSA. Thus, in
      contrast to PSA, interpretation of AFP, CEA, CA 15-3 serum levels is not
      influenced by recent CPR.

PMID- 16882123
TI  - Risk of colorectal cancer in general practice patients presenting with rectal
      bleeding, change in bowel habit or anaemia.
AB  - The aim was to use data routinely collected in general practice to assess the
      absolute risk of colorectal cancer in patients newly presenting to their general
      practitioner (GP) with relevant symptoms. Three cohorts were identified from
      patients attending a sample of UK general practices. Patients with new symptoms
      of rectal bleeding, changes in bowel habit or anaemia were identified, and their
      incident rate for colorectal cancer and the positive predictive value (PPV) of
      each symptom in the following 12 months were calculated by age and gender. The
      total population over the age of 40 years was 2.8 million, and 9143 incident
      cases of colorectal cancer were identified. A total of 67,164 patients (28% men)
      were identified with anaemia, 27,524 (40% men) with changes in bowel habit and
      44,741 (48% men) with rectal bleeding. For each cohort, the absolute risk rose
      with increasing age, and men were twice as likely to develop colorectal cancer.
      The PPV for developing colorectal cancer in the subsequent 12 months in those
      aged 60-69 years with anaemia was 3.02% for men, 1.38% for women; with changes in
      bowel habit 6.89% for men, 2.42% for women; and with rectal bleeding was 5.99%
      for men, 3.50% for women. A combination of any two signs and symptoms doubled the
      risk of an underlying cancer. In UK general practice, men are less likely to
      present with symptoms and signs of colorectal cancer compared with women, but
      after investigation are much more likely to have a colorectal cancer diagnosed.
      This should be taken into account in guidelines for referral.

PMID- 16882124
TI  - Lymphoma: variations in time to diagnosis and treatment.
AB  - This study examines illness trajectories of patients with lymphoma and assesses
      whether UK government targets to reduce waiting time for diagnosis and treatment
      are achievable and appropriate. One hundred and ninety-four patients, residents
      in West Yorkshire, aged more than 25 years and newly diagnosed with lymphoma
      during 2000 were included. Data collected from interviews, primary care and
      hospital records were used to examine time between critical events on the illness
      trajectory and characteristics of patients not meeting proposed targets. Forty
      two per cent of patients did not receive a hospital appointment within 2 weeks of
      general practitioner referral, 26% were not treated within 1 month of diagnosis
      and 64% were not treated within 2 months of referral. Target achievement differed
      by diagnostic group, and trends were seen by age and deprivation. The interval
      from onset of symptoms to treatment averaged more than 1 year and approximately
      half of this occurred before first medical contact. Results suggest that
      significant improvements are needed to achieve targets. Although existing targets
      particularly address referral and treatment intervals, these were the shortest
      intervals on the trajectory. Generalized targets may be inappropriate and
      unachievable for lymphoma as they do not consider individual disease
      characteristics or allow for variations in the urgency with which treatment is
      needed.

PMID- 16882125
TI  - What non-prescription treatments do UK women with breast cancer use?
AB  - Understanding the self-prescribing behaviours of patients as well as their
      attitudes towards prescribed medication regimens is essential if healthcare
      professionals are to support treatment adherence and avoid unwanted
      pharmacological interactions and compromises in treatment efficacy. Evidence
      shows that women with breast cancer are particularly likely to use complementary
      and alternative therapies. This paper describes the reported treatment profile of
      a sample of 208 women with breast cancer in the UK. The information was gathered
      as part of a study exploring the preferences for injection or tablets in the
      administration of breast cancer treatment. Almost two-thirds of the sample were
      currently taking prescribed breast cancer treatment, mostly a single hormone
      therapy. Prescribed medications for co-morbid diseases were also common, and 53%
      of the women were self-medicating mainly with supplements, principally vitamins,
      various oils and minerals. In line with other studies, higher levels of
      education, socio-economic status and internal locus of control were associated
      with non-prescription use as well as a body mass index <30.

PMID- 16882126
TI  - Analysis of clinical outcomes and prognostic factors of neoadjuvant
      chemoradiotherapy combined with surgery: intraperitoneal versus extraperitoneal
      rectal cancer.
AB  - Neoadjuvant chemoradiotherapy (CRT) is a widely purposed and performed treatment
      for rectal cancer. Downstaging effects possibly enhance the rate of curative
      surgery and may enable sphincter preservation in low-lying tumours. The current
      study examines the clinical outcomes in patients enrolled in a neoadjuvant CRT
      surgery protocol for rectal cancer, distinguishing between intraperitoneal and
      extraperitoneal cancer. From 1994 to 2003, 58 patients with a primary diagnosis
      of rectal cancer were enrolled in a single-centre, not randomized study based on
      5-week sessions of radiotherapy associated with a 30-day protracted venous 5-FU
      infusion followed by surgical resection. The study population was divided into
      two groups according to the localization of the tumour: 18 intraperitoneal and 40
      extraperitoneal (EPt). Fifty-eight patients were treated with neoadjuvant CRT and
      surgery. Overall mortality rate was 25.9%, no deaths were recorded during
      hospitalization; 10 patients (all EPt) died because of recurrence. Significant
      differences in disease-free survival and overall survival rates were found
      between intraperitoneal vs. extraperitoneal tumours (P = 0.006), both
      intraperitoneal vs. extraperitoneal tumours N(0) (P = 0.04 and P < 0.05) and
      intraperitoneal vs. extraperitoneal tumours N(+) (P < 0.05). We diagnosed all
      local recurrence and liver metastasis in extraperitoneal tumours (t = 0.02 and t
      = 0.04), and only one case of lung metastasis arose from intraperitoneal cancer.
      Extraperitoneal tumours could be more aggressive than intraperitoneal ones,
      spreading more precociously, and/or less responsive to the neoadjuvant CRT
      because of their localization rather than biological differences. Aside from
      lymph node status, the location of the tumour with respect to the peritoneum
      border, is also a prognostic factor of survival in rectal cancer treated by
      neoadjuvant CRT and surgery.

PMID- 16882127
TI  - Quality of life in newly diagnosed patients with lung cancer in a developing
      country: is it important?
AB  - There are no data regarding quality of life (QoL) assessments in lung cancer in
      developing countries like India. Quality of life was evaluated in 76 newly
      diagnosed lung cancer patients by using the World Health Organization Quality of
      Life questionnaire in Hindi (WHOQoL-Bref) (men 87%). The mean age was 55 years
      (SD = 10). Cough, dyspnoea, chest pain and haemoptysis were present in 83%, 72%,
      66% and 43% of patients respectively. The median duration of symptoms was 5.9
      months (range 1-13). Eighty-nine per cent had non-small cell lung cancer. The
      median pack-years smoked was 23 (range 0.5-88). Most patients (53%) had a
      Karnofsky's Performance Status (KPS) of 70 and 83% had stage III or IV disease.
      Quality of life did not correlate with age, gender, presence or duration of
      symptoms, histological type, stage of disease or degree of smoking. The physical
      and psychological domains of QoL correlated significantly with the KPS (P = 0.001
      and P = 0.01 respectively). Patients with a KPS of 80 had better physical (P <
      0.001), psychological (P < 0.01) and social (P < 0.05) QoL than those with a KPS
      of 70. In conclusion, patients with lung cancer in a developing country like
      India have an unsatisfactory QoL. The Karnofsky's Performance Scale is a simple
      and reliable surrogate marker for assessing QoL in these patients. Larger multi
      centric studies may help in providing a more comprehensive evaluation of the
      effect of various demographic and clinical variables on QoL in this setting.

PMID- 16882128
TI  - Intravenous ibandronate does not affect time to renal function deterioration in
      patients with skeletal metastases from breast cancer: phase III trial results.
AB  - As patients with metastatic bone disease typically receive long-term treatment
      with bisphosphonates, and often antineoplastic compounds, drug-related safety is
      of considerable importance. Clinical trial data for intravenous (i.v.)
      ibandronate suggest that its nephrotoxic potential is comparable with placebo. We
      conducted a post hoc Kaplan-Meier analysis of time to serum creatinine increase
      with i.v. ibandronate throughout 2 years of treatment. After 96 weeks, 12% of
      patients in the placebo group and 6% in the ibandronate 6 mg group (ns, P = 0.22)
      had defined serum creatinine increases. After 12 treatment months (48 weeks), 4%
      of patients receiving placebo and 2% of patients receiving ibandronate 6 mg
      showed increased serum creatinine. These results suggest that there is no
      clinically relevant change in serum creatinine levels with i.v. ibandronate 6 mg
      infused every 3-4 weeks for 2 years. Comparative trials to examine the renal
      safety of ibandronate and other i.v. bisphosphonates are warranted.

PMID- 16882130
TI  - Primary cardiac non-Hodgkin lymphoma presenting with atrial flutter and
      pericardial effusion.

PMID- 16882132
TI  - Acquired resistance to activated protein C (aAPCR) in multiple myeloma is a
      transitory abnormality associated with an increased risk of venous
      thromboembolism.
AB  - Acquired activated protein C resistance (aAPCR), not associated with factor V
      Leiden, has been described in cancer patients with an increased risk of venous
      thromboembolism (VTE). APCR was determined in 1178 myeloma patients using an
      activated partial thromboplastin time-based resistance assay in the presence of
      excess of factor V-deficient plasma; polymerase chain reaction amplification of
      genomic DNA was used to detect factor V Leiden mutation. A total of 109 patients
      were found to have abnormal APCR and one-third of them were carriers for the
      mutation. With a median follow-up of 40 months, the presence of aAPCR was
      associated with a significantly increased risk of thrombosis (P < or = 0.001).
      APCR was measured again after treatment in 31 patients with abnormal baseline
      values and had normalised in 30 of them. This study indicates that aAPCR is the
      most common single transitory baseline coagulation abnormality associated with
      VTE in myeloma patients.

PMID- 16882131
TI  - Drug-induced cutaneous vasculitis in patients with non-Hodgkin lymphoma treated
      with the novel proteasome inhibitor bortezomib: a possible surrogate marker of
      response?
AB  - Bortezomib is the first proteasome inhibitor to be approved for use in
      haematological malignancies. Although a rash has been described as a common
      adverse event associated with the drug, it has not been well characterised. Based
      on three phase II studies of bortezomib in patients with non-Hodgkin lymphoma
      (140 assessable patients), we identified 26 patients who developed a unique
      erythematous maculopapular rash during treatment, six of whom underwent cutaneous
      biopsy. Punch biopsy in six patients revealed a perivascular lymphocytic
      infiltrate without evidence of lymphoma, consistent with a non-necrotising
      cutaneous vasculitis. The combined overall response rate was 41%. The response in
      the 26 patients who developed a rash was 73%, compared with 33% in patients who
      did not. The odds ratio for response given the development of a rash was 4.6 (95%
      CI, 1.7-12.4, P = 0.001). This is the first report to characterise a vasculitic
      rash associated with bortezomib, and to show a relationship between development
      of the rash and response to treatment. Unlike classic hypersensitivity type
      reactions, this vasculitic rash may not necessarily prompt cessation of drug. In
      fact, the development of an isolated cutaneous vasculitis may portend a better
      clinical response to bortezomib in some patients.

PMID- 16882133
TI  - The infectivity of transmissible spongiform encephalopathy agent at low doses:
      the importance of phospholipid.
AB  - The issue of whether the mechanism of infection is independent or co-operative
      for low doses of transmissible spongiform encephalopathy (TSE) agent is critical
      for risk assessment. The susceptibility (and hence ID(50)) of individuals with
      the same prion protein (PrP) genotype may vary considerably with a small
      proportion being very susceptible. Assuming independent action, the incubation
      period (IP) would continue to increase until the dose is below the ID(50) of the
      most susceptible individuals in the experiment, at which point it would become
      constant. This may explain the observed increase in IP with decreasing dose below
      the apparent ID(50) in experiments with untreated TSE agent. In contrast, IPs for
      autoclaved or NaOH-treated TSE agent increase greatly at doses <ID(50) suggesting
      strong co-operative action, or even a threshold. It is proposed here that the
      unit of infectivity for prion disease is a nucleation seed comprised of PrP and
      host phospholipid (PL). PL would play a structural role through mediating
      protein/lipid interactions with PrP. Heating or alkali treatment destroys the PL
      breaking up the nucleation seeds, which require long IPs to reform at low doses.
      Replenishing those inactivated PLs with host PL would explain how the phenotypic
      effect of long IP at low dose is lost on subpassage. It is proposed here that
      strain thermostability is controlled by the nature and strength of the PrP/PL
      interactions, which are independent of the host PrP genotype. Although repeated
      oral exposure to low doses of scrapie is less harmful than a single large
      exposure, this effect may reflect interference by competition rather than
      diminished risks due to a co-operative effect, and is of little importance for
      'one-off' low-dose environmental exposures.

PMID- 16882134
TI  - Mycelium cultivation, chemical composition and antitumour activity of a
      Tolypocladium sp. fungus isolated from wild Cordyceps sinensis.
AB  - AIMS: To examine and illustrate the morphological characteristics and growth
      kinetics of Cs-HK1, a Tolypocladium fungus, isolated from wild Cordyceps sinensis
      in solid and liquid cultures, and the major chemical constituents and antitumour
      effects of Cs-HK1 mycelium. METHODS AND RESULTS: The Cs-HK1 fungus was isolated
      from the fruiting body of a wild C. sinensis and identified as a Tolypocladium
      sp. fungus. It grew rapidly at 22-25 degrees C on a liquid medium containing
      glucose, yeast extract, peptone and major inorganic salts, with a specific growth
      rate of 1.1 day(-1), reaching a cell density of 23.0 g dw l(-1) in 7-9 days.
      Exopolysaccharides accumulated in the liquid culture to about 0.3 g l(-1) glucose
      equivalent. In comparison with natural C. sinensis, the fungal mycelium had
      similar contents of protein (11.7-microg) and carbohydrate (654.6-microg) but
      much higher contents of polysaccharide (244.2 mg vs 129.5 mg), adenosine (1116.8
      microg vs 264.6 microg) and cordycepin (65.7 microg vs 20.8 microg) (per gram dry
      weight). Cyclosporin A, an antibiotic commonly produced by Tolypocladium sp., was
      also detected from the mycelium extract. The hot water extract of mycelium showed
      low cytotoxic effect on B16 melanoma cells in culture (about 25% inhibition) but
      significant antitumour effect in animal tests, causing 50% inhibition of B16 cell
      induced tumour growth in mice. CONCLUSIONS: The Tolypocladium sp. fungus, Cs-HK1,
      can be easily cultivated by liquid fermentation. The mycelium biomass contained
      the major bioactive compounds of C. sinensis, and the mycelium extract had
      significant antitumour activity. SIGNIFICANCE AND IMPACT OF THE STUDY: The Cs-HK1
      fungus may be a new and promising medicinal fungus and an effective and
      economical substitute of the wild C. sinensis for health care.

PMID- 16882135
TI  - Isolation of Salmonella from environmental samples collected in the reptile
      department of Antwerp Zoo using different selective methods.
AB  - AIMS: To evaluate the environmental spread of Salmonella strains in the reptile
      department of Antwerp Zoo and to compare different isolation methods for
      Salmonella. METHODS AND RESULTS: One hundred environmental samples were collected
      in the service sections and public spaces of the reptile department. After pre
      enrichment in buffered peptone water (BPW), selective enrichment was performed in
      Rappaport Vassiliadis Single Component Enrichment Broth (RVS), Selenite Cystine
      Broth (SEL) and Mueller Kauffman Tetrathionate Broth (MKTTn). Subculturing on
      Modified Semisolid Rappaport-Vassiliadis (MSRV) Medium, and the combined use of
      immunomagnetic separation (IMS) and RVS was evaluated. The isolation media used
      were Hektoen Enteric Agar (HE), Phenol Red Brilliant Green Agar (BG) and Xylose
      Lysine Decarboxylase Agar (XLD). Salmonella strains were found in 47 samples
      (47.0%). Most isolations were made on HE after combined IMS/RVS enrichment. Sixty
      six Salmonella strains were serotyped, 29 belonged to Salmonella enterica ssp.
      enterica (I), 3 to ssp. salamae (II), 29 to ssp. arizonae or diarizonae (IIIa/b),
      4 to ssp. houtenae (IV) and 1 strain showed autoagglutination. In addition, a 10
      year survey (1995-2004) of Salmonella serovars isolated from reptiles at Antwerp
      Zoo is presented. CONCLUSIONS: A high prevalence of Salmonella strains was noted
      in the service sections of the reptile department. Only a few isolations were
      made in the public spaces. Selective enrichment in RVS was the most efficient. In
      combination with IMS, this method gave an even higher isolation rate than the
      International Standard method (ISO 6579:2002). SIGNIFICANCE AND IMPACT OF THE
      STUDY: This study confirms the importance of reptiles as spreaders of Salmonella
      in their surroundings. The possible infectious risks for zoo personnel and
      visitors are evaluated. Improved laboratory protocols for the isolation of
      Salmonella from the environment are suggested.

PMID- 16882137
TI  - Modification of a virulence-associated phenotype after growth of Listeria
      monocytogenes on food.
AB  - AIM: To assess the effect of different foods, which have been implicated or not
      in cases of listeriosis, on the in vitro virulence-associated phenotype level of
      different Listeria monocytogenes strains. METHODS AND RESULTS: The virulence
      associated phenotype level of L. monocytogenes was studied with the in vitro cell
      test based on a plaque-forming assay with a human adenocarcinoma cell line (HT
      29) monolayer. Three strains of L. monocytogenes were grown in preparations
      (homogenate, 1-mum filtrate or 0.2-mum filtrate) of different food extracts
      ['rillettes' (potted minced pork), milk, raw salmon and cold-smoked salmon] or in
      a control medium, brain heart infusion (BHI). The bacterial suspensions grown in
      food extracts or in BHI at 37 degrees C were diluted with their growth medium
      (food extract or BHI) or with minimum essential medium before seeding on
      confluent HT-29 cell monolayers. Filtration of food extracts had no significant
      effect on the plaque numbers formed by the bacteria. A significant decrease in
      the plaque numbers was noted for the three strains when they grew in the
      rillettes extracts, compared with the other food extracts and BHI. The levels of
      in vitro virulence-associated phenotype of the strains after growth in the
      rillettes extract were similar to or lower than that of the hypovirulent internal
      reference strain L. monocytogenes 442. After growth in milk and cold-smoked
      salmon, the impact on virulence-associated phenotype depended on the strain. In
      contrast, plaque-forming assay indicated increased virulence-associated phenotype
      when the strains were switched from a nutrient-rich medium (food extract or BHI)
      to a minimum essential medium. CONCLUSIONS: In vitro virulence-associated
      phenotype level of the studied strains grown in BHI or cold-smoked salmon was the
      same as the control virulent strain EGD. In contrast, the nutrients present in
      rillettes may therefore substantially reduce the number of plaques but not the
      growth of L. monocytogenes. The utilization of minimum essential medium as
      diluent attenuates changes the effect of the food extract on virulence-associated
      phenotype in vitro. SIGNIFICANCE AND IMPACT OF THE STUDY: In the experimental
      design of this study, we showed that the nature of the food could affect the in
      vitro virulence-associated phenotype level of L. monocytogenes.

PMID- 16882136
TI  - Acidophilic microbial communities associated with a natural, biodegraded
      hydrocarbon seepage.
AB  - Characterization of microbial communities present in a surface petroleum seep in
      which hydrocarbons have been biodegraded for thousands of years in order to
      improve the understanding on natural petroleum biodegradation. DNA was extracted
      from a natural, surface petroleum seep and subjected to culture independent
      analysis (rRNA gene-based denaturing gradient gel electrophoresis and
      phylogenetic analysis of clone libraries). Molecular analysis suggested dominance
      by acidophilic bacteria, especially Alphaproteobacteria (mainly bacteria related
      to Acidiphilium and Acidocella). Archaea were not detected, but fungi were
      present. pH of the samples was around 3.5. Acidophilic microbial communities are
      associated with an acidic petroleum seep. Microbial community structure analysis
      gives information on the environmental conditions under which petroleum
      biodegradation occurs. This knowledge could be applied to define conditions for
      specific cultivation or activity measurements. The activity of acidophilic micro
      organisms deserves more attention with respect to their involvement in natural
      petroleum degradation. This knowledge will contribute to the design of oil
      bioremediation strategies for polluted acidic settings.

PMID- 16882138
TI  - Semiquantitative assessment of the distribution of Salmonella in the environment
      of caged layer flocks.
AB  - AIMS: To evaluate a semiquantitative technique for the enumeration of Salmonella
      in the environment of layer flocks and to compare findings with those of a
      standard qualitative technique. METHODS AND RESULTS: Samples were taken from
      faeces, floor dust, dust on cages, feeders and egg belts. After mixing with
      buffered peptone water, serial dilutions were prepared and culture was performed
      using pre-enrichment, then plating on semisolid selective and solid isolation
      media. Comparison with a qualitative pre-enrichment technique indicated a similar
      sensitivity for both methods despite smaller sample sizes. The numbers of
      Salmonella detected for a site or sample type did not correlate closely with the
      prevalence of positive samples. CONCLUSIONS: The sensitive detection and
      quantification of Salmonella in the flock environment is practicable with the
      technique described. Quantitative data in many cases do not correlate with
      qualitative findings. SIGNIFICANCE AND IMPACT OF THE STUDY: The significance of
      certain environmental factors and interventions in the maintenance and
      dissemination of Salmonella in poultry houses may be over- or under-represented
      by prevalence data alone. The technique described allows the issue of poultry
      house contamination to be examined from a new perspective.

PMID- 16882139
TI  - Influence of starvation, surface attachment and biofilm growth on the biocide
      susceptibility of the biodeteriogenic yeast Aureobasidium pullulans.
AB  - AIM: To investigate the effect of starvation, surface attachment and growth in a
      biofilm on the susceptibility of Aureobasidium pullulans to the biocides 2-n
      octyl-4-isothiazolin-3-one (OIT) and sodium hypochlorite (NaOCl). METHODS AND
      RESULTS: Fluorescence loss from a green fluorescent protein (GFP)-transformed
      strain was used to monitor real-time loss in viability as previously described in
      situ in 96-well plates. Exponential phase, yeast-like (YL) cells were settled in
      the bottom of the wells as a low-density monolayer (LDM) and were susceptible to
      all biocide concentrations (25-100 mug ml(-1)). The exponential phase YL cells
      were either starved for 48 h in suspension or starved for 48 h as LDMs in the
      wells. Starvation in both cases led to a small reduction in susceptibility to the
      biocides. In contrast, 48-h biofilms grown in malt extract broth showed an
      apparent lack of susceptibility to 25 and 50 mug ml(-1) OIT and to 25-100 mug ml(
      1) NaOCl. However, when the OIT concentration was increased to compensate for the
      higher cell density in the biofilm, the biofilms were found to be equally
      susceptible to the LDM. CONCLUSIONS: Starvation of A. pullulans YL cells either
      in suspension or as attached LDM resulted in a decrease in susceptibility to low
      concentrations of both OIT and NaOCl while the apparent reduced susceptibility of
      mature biofilms was due to the increase in biofilm cell density rather than true
      biofilm resistance per se. SIGNIFICANCE AND IMPACT OF THE STUDY: Monitoring
      fluorescence loss from the GFP-transformed strain of A. pullulans can be used as
      a fast and reliable method for monitoring cell death in real time as a response
      to biocide and antimicrobial challenge.

PMID- 16882140
TI  - Changes in bacterial community during fermentative hydrogen and acid production
      from organic waste by thermophilic anaerobic microflora.
AB  - AIMS: Changes in fermentation pattern during the treatment of organic wastes
      containing solid materials by thermophilic anaerobic microflora were investigated
      with respect to product formation and bacterial community structure during
      hydrogen production. METHODS AND RESULTS: Anaerobic microflora enriched from
      sludge compost was cultivated using artificial garbage slurry in a continuous
      flow-stirred tank reactor. Product formation varied depending on pH and hydraulic
      retention time (HRT) applied. Community analysis by terminal restriction fragment
      length polymorphism and clone library analysis of polymerase chain reaction
      amplified bacterial 16S rDNA indicated that difference in the fermentative
      product distribution could be caused by different populations of micro-organisms
      in the microflora. CONCLUSION: Hydrogen fermentation with acetate/butyrate
      formation was optimized at <1.0 d HRT at pH 5.0 and 6.0. Thermoanaerobacterium
      thermosaccharolyticum was the dominant hydrogen-producing micro-organism.
      Conversely, unidentified organisms became dominant after 4.0 d HRT at pH 7.0 and
      8.0, where relatively high-solubilization efficiency of solid materials was
      observed with no production of hydrogen. SIGNIFICANCE AND IMPACT OF THE STUDY:
      This is the first report describing product formation in the fermentation of
      solid organic wastes by a mixed population of micro-organisms. Various
      fermentation patterns including hydrogen fermentation were characterized and
      evaluated from engineering and microbial aspects.

PMID- 16882141
TI  - A marked enhancement in phytase production by a thermophilic mould Sporotrichum
      thermophile using statistical designs in a cost-effective cane molasses medium.
AB  - AIMS: Statistical optimization of phytase production by a thermophilic mould
      Sporotrichum thermophile in a cost-effective cane molasses medium. METHODS AND
      RESULTS: Sporotrichum thermophile secreted phytase in cane molasses medium at 45
      degrees C and 250 rev min(-1) after 5 days. The important factors identified by
      Plackett-Burman design (magnesium sulfate, Tween 80, ammonium sulfate and
      incubation period) were further optimized by response surface methodology (RSM).
      An overall 107% improvement in phytase production was achieved due to
      optimization. Supplementation of the medium with inorganic phosphate repressed
      the enzyme synthesis. When inorganic phosphate was reduced from the cane molasses
      medium by treatment with calcium chloride, the enzyme production increased. The
      phytase activity was not affected by the enzyme treatment with trypsin and
      pepsin. CONCLUSIONS: A twofold increase in phytase production was achieved due to
      optimization using statistical designs in a cost-effective cane molasses medium.
      SIGNIFICANCE AND IMPACT OF THE STUDY: Phytase production was doubled due to
      optimization. The enzyme, being resistant to trypsin and pepsin, thermostable and
      acid stable, can find application in animal feed industry for improving
      nutritional status of the feed and combating environmental phosphorus pollution.

PMID- 16882142
TI  - Characterization of the Enterobacteriaceae isolated from an artisanal Italian
      ewe's cheese (Pecorino Abruzzese).
AB  - AIMS: To evaluate some physiological characteristics of the Enterobacteriaceae
      isolated from Pecorino cheese. METHODS AND RESULTS: The production of organic
      acids, secondary volatile compounds, biogenic amines (BA) and the lipolytic and
      proteolytic activities of Citrobacter braakii, Enterobacter sakazakii,
      Escherichia coli, Kluyvera spp., Salmonella enterica ssp. arizonae and Serratia
      odorifera strains were determined in skim milk after 48 h of fermentation at 30
      degrees C. The proteolytic activity observed only in Ser. odorifera and Kluyvera
      spp. was confirmed by the peptide profiles of the pH 4.6-insoluble fraction using
      RP-HPLC; however, the lipase activity was evidenced in all the isolates of E.
      coli, Kluyvera spp. and Salm. enterica ssp. arizonae. During fermentation, all
      the strains utilized citric acid and produced significant quantities of
      putrescine followed by histamine, spermine and spermidine as well as acetic and
      lactic acid. Moreover, the major volatile compounds produced were ethanol, 2,3
      butanedione, 3-hydroxy-2-butanone, 2-heptanone and acetone. CONCLUSIONS: The
      Enterobacteriaceae of dairy origin possess many metabolic activities that could
      affect the sensory quality of the cheese in which they grow during ripening.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The important physiological characteristics
      possessed by Enterobacteriaceae confirm the complexity of the microbiota of
      Pecorino Abruzzese cheese, which influences the typical sensory properties of
      this product.

PMID- 16882143
TI  - Prevalence of enterohaemorrhagic Escherichia coli from serotype O157 and other
      attaching and effacing Escherichia coli on bovine carcasses in Algeria.
AB  - AIMS: Bovine meat is the principal source of human contamination of attaching and
      effacing Escherichia coli, including enterohaemorrhagic E. coli O157. The aim was
      to study the prevalence of these strains on bovine carcasses in Algeria. METHODS
      AND RESULTS: Two-hundred and thirty carcasses were swabbed and analysed by
      classical microbiological methods for total E. coli counts and for the presence
      of pathogenic E. coli. The E. coli counts were high, with a 75th percentile of
      444.75 CFUs cm(-2). For pathogenic E. coli, more than 7% of the tested carcasses
      were positive for E. coli O157. Eighteen E. coli O157 strains were isolated and
      typed by multiplex PCR. The main isolated pathotype (78%) was eae+ stx2+ ehxA+.
      In addition to E. coli O157, other attaching and effacing E. coli (AEEC) were
      also detected from carcasses by colony hybridization after pre-enrichment and
      plating on sorbitol MacConkey agar using eae, stx1 and stx2 probes. Thirty
      carcasses (13%) on the 230 analysed harboured at least one colony positive for
      one of the tested probes. These positive carcasses were different from those
      positive for E. coli O157. Sixty-six colonies (2.9%) positive by colony
      hybridization were isolated. The majority (60.6%) of the positive strains
      harboured an enteropathogenic E. coli-like pathotype (eae+ stx-). Only three
      enterohaemorrhagic E. coli (EHEC)-like (eae+ stx1+) colonies were isolated from
      the same carcass. These strains did not belong to classical EHEC serotypes.
      CONCLUSIONS: In this study, the global hygiene of the slaughterhouse was low, as
      indicated by the high level of E. coli count. The prevalence of both E. coli O157
      and other AEEC was also high, representing a real hazard for consumers.
      SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first study of this type in
      Algeria, which indicates that the general hygiene of the slaughterhouse must be
      improved.

PMID- 16882144
TI  - Specific detection of prion antigenic determinants retained in bovine meat and
      bone meal by flow microbead immunoassay.
AB  - AIMS: The purpose of this study was to develop an effective method for detecting
      prion (PrP) antigenic determinants remaining in bovine meat and bone meal (MBM)
      using pressurized fluid extraction (PSE) equipment and flow microbead immunoassay
      (FMI). METHODS AND RESULTS: Using the FMI, bovine recombinant PrP could be
      determined quantitatively in the 7 pmol-7 nmol range using anti-PrP peptide
      polyclonal antibody-coupled microbeads and anti-PrP monoclonal antibody (SAF61)
      as a detection antibody. PSE extraction at 120 degrees C for 5 min under high
      pressure was most effective for eluting PrP determinants from bovine MBMs. The
      FMI was capable of detecting PrP determinants in bovine MBM extracts with high
      specificity and indicated that the MBMs contained high levels of PrP
      determinants. This assay was also applied to the detection of PrP(Sc)
      determinants in bovine MBM spiked with a scrapie-infected brain at a weight ratio
      of 50 : 1. CONCLUSIONS: These data indicate that this assay was effective for the
      specific detection of PrP determinants contained in bovine MBM extracts.
      SIGNIFICANCE AND IMPACT OF THE STUDY: To our knowledge, this is the first report
      detailing the detection of PrP determinants in bovine MBM. The assay could be
      applied to securing the safety of bovine MBM.

PMID- 16882145
TI  - Bovine whey proteins inhibit the interaction of Staphylococcus aureus and
      bacteriophage K.
AB  - AIMS: To understand the potential use of bacteriophage K to treat bovine
      Staphylococcus aureus mastitis, we studied the role of whey proteins in the
      inhibition of the phage-pathogen interaction in vitro. METHODS AND RESULTS: The
      interaction of bacteriophage K and S. aureus strain Newbould 305 was studied in
      raw bovine whey and serum. Incubation of S. aureus with phage in whey showed that
      the bacteria are more resistant to phage lysis when grown in whey and also bovine
      serum. Whey collected from 23 animals showed a wide variation in the level of
      phage-binding inhibition. The role of the protein component of milk whey in this
      inhibition was established; treatment of the whey by heat, proteases and
      ultrafiltration removed the inhibitory activity. Brief exposure of S. aureus
      cells to whey, followed by resuspension in broth, also reduced phage binding.
      Microscopy showed the adhesion of extracellular material to the S. aureus cell
      surface following exposure to whey. Chromatographic fractionation of the whey
      demonstrated that the inhibitory proteins were present in the high molecular
      weight fraction. CONCLUSIONS: The adsorption of whey proteins to the S. aureus
      cell surface appeared to inhibit phage attachment and thereby hindered lysis. The
      inhibitory whey proteins are of high molecular weight in their native form and
      may sterically block phage attachment sites on the cell surface. SIGNIFICANCE AND
      IMPACT OF THE STUDY: These findings have implications for any future use of phage
      therapy in the treatment of mastitis, and other diseases, caused by S. aureus.
      This pathogen is predicted to be much more resistant to phage treatment in vivo
      than would be expected from in vitro broth culture experiments.

PMID- 16882146
TI  - Characterizing a stable methane-utilizing mixed culture used in the synthesis of
      a high-quality biopolymer in an open system.
AB  - AIMS: To characterize a methane-utilizing poly-beta-hydroxybutyrate (PHB)
      producing microbial community. METHODS AND RESULTS: Three different approaches
      based on microbiology, analytical chemistry and molecular biology were used to
      determine the composition of the mixed culture. The dominant species,
      Methylocystis sp. GB25, represents more than 86% of the total biomass. Seven
      accompanying bacterial species are present in the mixed culture of which two are
      methylotrophic bacteria and five are utilizers of complex carbon sources. Both
      these groups were found to be present at the same ratio with respect to each
      other. Results of fatty acid analysis and PCR-DGGE fingerprints reflect the
      stability of the mixed-culture composition in the open system during multiple
      continuous growth and polymer formation processes throughout a period of 29
      months. The consistently high quality of the accumulated polymer further
      corroborates this finding. CONCLUSION: The methane-utilizing mixed culture has
      the potential of self-regulation resulting in a stable composition even under non
      aseptic conditions. SIGNIFICANCE AND IMPACT OF THE STUDY: Avoiding the necessity
      of sterile conditions, as demonstrated in this paper, is an important step
      towards the development of a viable large-scale process for the production of PHB
      using cheap substrates like methane from natural or renewable sources. This is
      the first report characterizing a bacterial mixed culture being used for the
      biotechnological production of a high-value product in an open system.

PMID- 16882147
TI  - Phenotypic and molecular characterization of Lactococcus lactis from milk and
      plants.
AB  - AIMS: The aim of this study was to obtain new Lactococcus lactis strains from
      nondairy materials for use as milk fermentation starters. The genetic and
      phenotypic traits of the obtained strains were characterized and compared with
      those of L. lactis strains derived from milk. It was confirmed that the plant
      derived bacteria could be used as milk fermentation starters. METHODS AND
      RESULTS: About 2600 lactic acid bacteria were subjected to screening for L.
      lactis with species-specific PCR. Specific DNA amplification was observed in 106
      isolates. Forty-one strains were selected, including 30 strains of milk-derived
      and 11 of plant-derived, and their phenotypic traits and genetic profiles were
      determined. The plant-derived strains showed tolerance for high salt
      concentration and high pH value, and fermented many more kinds of carbohydrates
      than the milk-derived strains. There were no remarkable differences in the
      profiles of enzymes, such as lipases, peptidases and phosphatases. Isolates were
      investigated by cluster analysis based on randomly amplified polymorphic DNA
      profiles. There were no significant differences between isolates from milk and
      those from plant. The L. lactis subsp. cremoris strains were clustered into two
      distinct groups, one composed of the strains having the typical cremoris
      phenotype and the other composed of strains having a phenotype similar to subsp.
      lactis. Fermented milk manufactured using the plant-derived strains were not
      inferior in flavour to that manufactured using the milk-derived strains.
      CONCLUSIONS: Plant-derived L. lactis strains are genetically close to milk
      derived strains but have various additional capabilities, such as the ability to
      ferment many additional kinds of carbohydrates and greater stress-tolerance
      compared with the milk-derived strains. SIGNIFICANCE AND IMPACT OF THE STUDY: The
      lactic acid bacteria obtained from plants in this study may be applicable for use
      in the dairy product industry.

PMID- 16882148
TI  - Impact of winemaking practices on arginine and citrulline metabolism during and
      after malolactic fermentation.
AB  - AIMS: To study arginine degradation and carcinogenic ethyl carbamate precursor
      citrulline formation during and after malolactic fermentation (MLF). METHODS AND
      RESULTS: MLF was induced in white wine with two commercial Oenococcus oeni
      strains under different winemaking conditions regarding the type of alcoholic
      fermentation (spontaneous, induced) and the lees management (racked, on lees).
      Arginine degradation and citrulline formation did not occur during malic acid
      degradation in any treatment. In five of the six treatments in which arginine
      degradation took place, it occurred 3 weeks after malic acid depletion and
      significant amounts of citrulline were formed. Presence of yeast lees in wines
      led to increased citrulline formation. CONCLUSIONS: This study suggests that
      arginine metabolism is inhibited in oenococci at low pH values (< 3.5) and that
      in the postalcoholic fermentation phase, citrulline formation from arginine
      degradation can be avoided if MLF is induced by pure cultures of O. oeni with
      inhibition of the bacterial biomass after malic acid depletion. Residual yeast
      lees in the wine have been identified as a significant risk factor for increased
      citrulline formation. SIGNIFICANCE AND IMPACT OF THE STUDY: Conclusions drawn
      from this study allow reducing the risk of carcinogenic ethyl carbamate formation
      from citrulline excretion by wine lactic acid bacteria.

PMID- 16882150
TI  - Inhibition of Bacillus licheniformis LMG 19409 from ropy cider by enterocin AS
      48.
AB  - AIMS: To determine the activity of enterocin AS-48 against ropy-forming Bacillus
      licheniformis from cider. METHODS AND RESULTS: Enterocin AS-48 was tested on B.
      licheniformis LMG 19409 from ropy cider in MRS-G broth, fresh-made apple juice
      and in two commercial apple ciders (A and B). Bacillus licheniformis was rapidly
      inactivated in MRS-G by 0.5 microg ml(-1)AS-48 and in fresh-made apple juice by 3
      microg ml(-1). Concentration-dependent inactivation of this bacterium in two
      commercial apple ciders (A and B) stored at 4, 15 and 30 degrees C for 15 days
      was also demonstrated. Counts from heat-activated endospores in cider A plus AS
      48 decreased very slowly. Application of combined treatments of heat (95 degrees
      C) and enterocin AS-48 reduced the time required to achieved complete
      inactivation of intact spores in cider A to 4 min for 6 microg ml(-1) and to 1
      min for 12 microg ml(-1). D and z values also decreased as the bacteriocin
      concentration increased. CONCLUSION: Enterocin AS-48 can inhibit ropy-forming B.
      licheniformis in apple cider and increase the heat sensitivity of spores.
      SIGNIFICANCE AND IMPACT OF THE STUDY: Results from this study support the
      potential use of enterocin AS-48 to control B. licheniformis in apple cider.

PMID- 16882149
TI  - Systemic movement of Agrobacterium tumefaciens in several plant species.
AB  - AIMS: The systemic movement of Agrobacterium spp. inside plants of different
      species was studied to determine the most valuable diagnostic methodology for
      their detection. METHODS AND RESULTS: Pathogenic agrobacteria were detected by
      isolation and PCR in tissue away from primary tumours in tomato plants grown in
      the presence of Agrobacterium spp. Moreover, this bacterium was also able to
      induce secondary tumours beyond the inoculation site. In addition, the capacity
      of agrobacteria to translocate and induce secondary tumours was analysed in rose,
      grapevine, chrysanthemum, cherry and peach x almond hybrid GF677. No differences
      among strains of Agrobacterium spp. were detected in secondary tumour
      development, although some of them induced a significantly higher number of
      primary tumours in some species. Movement of inoculated pathogenic cells of four
      strains was also demonstrated in symptomless portions of the plant stems by
      isolation and PCR. Finally, pathogenic agrobacteria were detected in root, crown
      and stem portions of naturally infected walnuts. In all assays, PCR was the most
      efficient technique for detecting the movement of Agrobacterium spp. within the
      plants. CONCLUSIONS: Migration of agrobacteria inside plants is a complex
      phenomenon and more extensive than previously reported. Therefore, efficient and
      sensitive detection methods such as PCR must be used to select clean plants to
      avoid latent infections of Agrobacterium spp. SIGNIFICANCE AND IMPACT OF THE
      STUDY: The results show that migration of Agrobacterium spp. could be relatively
      frequent in several cultivated fruit trees, and systemic infections should be
      taken into account when designing strategies for controlling crown gall disease.

PMID- 16882151
TI  - Soil survival of Escherichia coli O157:H7 acquired by a child from garden soil
      recently fertilized with cattle manure.
AB  - AIMS: This investigation was conducted to determine the survival of a naturally
      occurring Escherichia coli O157:H7 in garden soil linked to a sporadic case of E.
      coli O157 infection in Minnesota. METHODS AND RESULTS: The presence and viability
      of E. coli O157:H7 was monitored in manure-contaminated garden soil for several
      weeks. Bacterial isolates were characterized using PCR and pulsed-field gel
      electrophoresis (PFGE). Isolates obtained from the patient and the garden plots
      during this investigation had indistinguishable PFGE patterns and had the same
      virulence factors (stx1, stx2, eaeA, ehxA). The E. coli O157:H7 levels obtained
      from the garden plots declined gradually for a period of 2 months, and on day 69
      only one garden plot of four had detectable levels of pathogen. All plots were
      negative on day 92. The rate of decline in the soil samples stored at 4 degrees C
      was faster compared with soil samples that remained in ambient conditions, and in
      refrigerated storage E. coli O157:H7 could not be detected after 10 days.
      CONCLUSIONS: E. coli O157:H7 strains can survive on manure-amended soil for more
      than 2 months, and this survival could be reduced by low temperature.
      SIGNIFICANCE AND IMPACT OF THE STUDY: This is one of the few reports that have
      investigated the survival of a proven virulent strain in naturally contaminated
      soil samples. This case stresses the importance of avoiding the use of raw cattle
      manure to amend soil for cultivation of foods, including soils in residential
      garden plots.

PMID- 16882152
TI  - Effect of flow regimes on the presence of Legionella within the biofilm of a
      model plumbing system.
AB  - AIMS: Stagnation is widely believed to predispose water systems to colonization
      by Legionella. A model plumbing system was constructed to determine the effect of
      flow regimes on the presence of Legionella within microbial biofilms. METHODS AND
      RESULTS: The plumbing model contained three parallel pipes where turbulent,
      laminar and stagnant flow regimes were established. Four sets of experiments were
      carried out with Reynolds number from 10,000 to 40,000 and from 355 to 2,000 in
      turbulent and laminar pipes, respectively. Legionella counts recovered from
      biofilm and planktonic water samples of the three sampling pipes were compared
      with to determine the effect of flow regime on the presence of Legionella.
      Significantly higher colony counts of Legionella were recovered from the biofilm
      of the pipe with turbulent flow compared with the pipe with laminar flow. The
      lowest counts were in the pipe with stagnant flow. CONCLUSIONS: We were unable to
      demonstrate that stagnant conditions promoted Legionella colonization.
      SIGNIFICANCE AND IMPACT OF THE STUDY: Plumbing modifications to remove areas of
      stagnation including deadlegs are widely recommended, but these modifications are
      tedious and expensive to perform. Controlled studies in large buildings are
      needed to validate this unproved hypothesis.

PMID- 16882153
TI  - The microbial degradation of azimsulfuron and its effect on the soil bacterial
      community.
AB  - AIMS: Azimsulfuron is a recently introduced sulfonylurea herbicide useful in
      controlling weeds in paddy fields. To date very little information is available
      on the biodegradation of this pesticide and on its effect on the soil microbial
      community. The aim of this work was to study its biodegradation both in slurry
      soil microcosms and in batch tests with mixed and pure cultures. METHODS AND
      RESULTS: Azimsulfuron was applied to forest bulk soil in order to study its
      effect on the structure of the bacterial soil community, as detectable by
      denaturant gradient gel electrophoresis (DGGE) analyses. Biodegradation and
      abiotic processes were investigated by HPLC analyses. In addition, a microbial
      consortium was selected, that was able to use azimsulfuron as the sole energy and
      carbon source. One of the metabolites produced by the consortium was isolated and
      identified through LC-MS analyses. Cultivable bacteria of the consortium were
      isolated and identified by 16S rDNA sequencing (1400 bp). CONCLUSIONS:
      Azimsulfuron treatment seems to have the ability to cause changes in the
      bacterial community structure that are detectable by DGGE analyses. It is easily
      biodegraded both in microcosms and in batch tests, with the formation of an
      intermediate that was identified as 2-methyl-4-(2-methyl-2H-tetrazol-5-yl)-2H
      pyrazole-3-sulfonamide. SIGNIFICANCE AND IMPACT OF THE STUDY: The study increases
      the knowledge on the biodegradation of azimsulfuron and its effects on the soil
      microbiota.

PMID- 16882154
TI  - Batch solar disinfection inactivates oocysts of Cryptosporidium parvum and cysts
      of Giardia muris in drinking water.
AB  - AIM: To determine whether batch solar disinfection (SODIS) can be used to
      inactivate oocysts of Cryptosporidium parvum and cysts of Giardia muris in
      experimentally contaminated water. METHODS AND RESULTS: Suspensions of oocysts
      and cysts were exposed to simulated global solar irradiation of 830 W m(-2) for
      different exposure times at a constant temperature of 40 degrees C. Infectivity
      tests were carried out using CD-1 suckling mice in the Cryptosporidium
      experiments and newly weaned CD-1 mice in the Giardia experiments. Exposure times
      of > or =10 h (total optical dose c. 30 kJ) rendered C. parvum oocysts
      noninfective. Giardia muris cysts were rendered completely noninfective within 4
      h (total optical dose >12 kJ). Scanning electron microscopy and viability (4',6
      diamidino-2-phenylindole/propidium iodide fluorogenic dyes and excystation)
      studies on oocysts of C. parvum suggest that inactivation is caused by damage to
      the oocyst wall. CONCLUSIONS: Results show that cysts of G. muris and oocysts of
      C. parvum are rendered completely noninfective after batch SODIS exposures of 4
      and 10 h (respectively) and is also likely to be effective against waterborne
      cysts of Giardia lamblia. SIGNIFICANCE AND IMPACT OF THE STUDY: These results
      demonstrate that SODIS is an appropriate household water treatment technology for
      use as an emergency intervention in aftermath of natural or man-made disasters
      against not only bacterial but also protozoan pathogens.

PMID- 16882155
TI  - Prevention of Salmonella cross-contamination in an oilmeal manufacturing plant.
AB  - AIMS: The mechanisms of Salmonella contamination in an oilmeal plant were
      investigated and the basic data were collected in order to achieve control of
      Salmonella in oilmeal. METHODS AND RESULTS: Salmonella was detected in all
      contamination vectors and environmental factors investigated, namely: operators,
      processing floor, dust in the air and rodents. In particular, high concentrations
      of Salmonella were detected on the processing floor of the manufacturing area,
      which has high oil content. Steam was the most effective disinfection method used
      for the processing floor, as the effects of heat sterilization and disinfection
      may work in tandem. In addition, restricting the movement of operators of the
      production chain remarkably reduced Salmonella contamination, even in areas of
      otherwise high contamination. CONCLUSIONS: Within the oilmeal plant, high
      Salmonella contamination rates for the processing floor represent the greatest
      risk of contamination of oilmeal via operators, dust in the air and rodents.
      Therefore, control of the processing floor is the most important means for
      reducing the oilmeal contamination rate. SIGNIFICANCE AND IMPACT OF THE STUDY:
      Specific Salmonella control methods for oilmeal plants have been established.

PMID- 16882156
TI  - Degradation of free and sulfur-dioxide-bound acetaldehyde by malolactic lactic
      acid bacteria in white wine.
AB  - AIMS: Acetaldehyde is the major carbonyl compound formed during winemaking and
      has implications for sensory and colour qualities of wines as well as for the use
      of the wine preservative SO(2). The current work investigated the degradation of
      acetaldehyde and SO(2)-bound acetaldehyde by two commercial Oenococcus oeni
      starters in white wine. METHODS AND RESULTS: Wines were produced by alcoholic
      fermentation with commercial yeast and adjusted to pH 3.3 and 3.6. While
      acetaldehyde was degraded rapidly and concurrently with malic acid at both pH
      values, SO(2)-bound acetaldehyde caused sluggish bacterial growth. Strain
      differences were small. CONCLUSIONS: Efficient degradation of acetaldehyde can be
      achieved by commercial starters of O. oeni. According to the results, the
      degradation of acetaldehyde could not be separated from malolactic conversion by
      oenococci. While this may be desirable in white winemaking, it may be necessary
      to delay malolactic fermentation (MLF) in order to allow for colour development
      in red wines. SO(2)-bound acetaldehyde itself maybe responsible for the sluggish
      or stuck MLF, and thus bound SO(2) should be considered next to free SO(2) in
      order to evaluate malolactic fermentability. SIGNIFICANCE AND IMPACT OF THE
      STUDY: The current study provides new results regarding the metabolism of
      acetaldehyde and SO(2)-bound acetaldehyde during the MLF in white wine. The
      information is of significance to the wine industry and may contribute to
      reducing the concentration of wine preservative SO(2).

PMID- 16882157
TI  - Enzymatic properties of two beta-glucosidases from Ceriporiopsis subvermispora
      produced in biopulping conditions.
AB  - AIMS: Ceriporiopsis subvermispora produces endoglucanase and beta-glucosidase
      when cultivated on cellulose or wood, but biodegradation of cellulose during
      biopulping by C. subvermispora is low even after long periods. To resolve this
      discrepancy, we grew C. subvermispora on Pinus taeda wood chips and purified the
      major beta-glucosidases it produced. Kinetic parameters were determined to clear
      if this fungus produces enzymes capable of yielding assimilable glucose from
      wood. METHODS AND RESULTS: Ceriporiopsis subvermispora was grown on P. taeda wood
      chips under solid-state fermentation. After 30 days, the crude extract obtained
      from enzyme extraction with sodium acetate buffer 50 mmol l(-1), pH 5.4, was
      filtrated in membranes with a molecular mass exclusion limit of 100 kDa. Enzyme
      purification was carried out using successively Sephacryl S-300 gel filtration.
      The retained fraction attained 76% of beta-glucosidase activity with 3.7-fold
      purification. Two beta-glucosidases were detected with molecular mass of 110 and
      53 kDa. We have performed a characterization of the enzymatic properties of the
      beta-glucosidase of 110 kDa. The optimum pH and temperature were 3.5 and 60
      degrees C, respectively. The K(m) and V(max) values were respectively 3.29 mmol
      l(-1) and 0.113 micromol min(-1) for the hydrolysis of p-nitrophenyl-beta
      glucopyranoside (pNPG) and 2.63 mmol l(-1) and 0.103 micromol min(-1), towards
      cellobiose. beta-Glucosidase activity was strongly increased by Mn(2+) and
      Fe(3+), while Cu(2+) severely inhibited it. CONCLUSIONS: Ceriporiopsis
      subvermispora produces small amounts of beta-glucosidase when grown on wood. The
      gel filtration and polyacrylamide gel electrophoresis data revealed the existence
      of two beta-glucosidases with 110 and 53 kDa. The 110 kDa beta-glucosidase from
      C. subvermispora can be efficiently purified in a single step by gel filtration
      chromatography. The enzyme has an acid pH optimum with similar activity on pNPG
      and cellobiose and is thus typical beta-glucosidase. SIGNIFICANCE AND IMPACT OF
      THE STUDY: Ceriporiopsis subvermispora produces beta-glucosidase with limited
      action during wood decay making able its use for the production of biomechanical
      and biochemical pulps. The results presented in this paper show the importance of
      studying the behaviour of beta-glucosidases during biopulping.

PMID- 16882158
TI  - Guaijaverin -- a plant flavonoid as potential antiplaque agent against
      Streptococcus mutans.
AB  - AIMS: The aim of the present study was to investigate the anti-Streptococcus
      mutans activity and the in vitro effects of subminimal inhibitory concentrations
      of guaijaverin isolated from Psidium guajava Linn. on cariogenic properties of
      Strep. mutans. METHODS AND RESULTS: Bioautography-directed chromatographic
      fractionation, yield biologically active compound, quercetin-3-O-alpha-l
      arabinopyranoside (guaijaverin), from crude methanol extract of P. guajava.
      Growth-inhibitory activity of the compound against Strep. mutans of both clinical
      and type strain cultures was evaluated. The anti-Strep. mutans activity of the
      guaijaverin was found to be bacteriostatic, both heat and acid stable and alkali
      labile with the minimum inhibitory concentration (MIC) of 4 mg ml(-1) for MTCC
      1943 and 2 mg ml(-1) for CLSM 001. The sub-MIC concentrations (0.0078-2 mg ml(
      1)) of the guaijaverin were evaluated for its cariogenic properties such as acid
      production, cell-surface hydrophobicity, sucrose-dependent adherence to glass
      surface and sucrose-induced aggregation of Strep. mutans. CONCLUSIONS: The active
      flavonoid compound, quercetin-3-O-alpha-l-arabinopyranoside (guaijaverin)
      demonstrated high potential antiplaque agent by inhibiting the growth of the
      Strep. mutans. SIGNIFICANCE AND IMPACT OF THE STUDY: This study demonstrated the
      new growth-inhibitory compound guaijaverin against Strep. mutans and led to the
      acceptance of traditional medicine and natural products as an alternative form of
      health care.

PMID- 16882159
TI  - Differences between Lactococcus garvieae isolated from the genus Seriola in Japan
      and those isolated from other animals (trout, terrestrial animals from Europe)
      with regard to pathogenicity, phage susceptibility and genetic characterization.
AB  - AIMS: To clarify the epidemiological relationship between Lactococcus garvieae
      isolates from the Seriola in Japan and isolates from other animals. METHODS AND
      RESULTS: A total of 32 isolates obtained from aquatic (the genus Seriola and
      trout) and terrestrial animals (cow, pig, cat, dog and horse) was used to
      evaluate its pathogenicity to yellowtail and mouse, phenotype (KG+ and KG-), its
      susceptibility to three bacteriophages and the pattern of pulsed field gel
      electrophoresis (PFGE). Lactococcus garvieae isolated from Seriola showed strong
      pathogenicity to yellowtail, while isolates from trout showed weak pathogenicity
      and those obtained from terrestrial animals showed no distinct pathogenicity.
      Only, the isolates from the genus Seriola in Japan showed susceptibility to the
      bacteriophages. The results of PFGE pattern indicate that the isolates obtained
      from the Seriola predict homogeneity, while there is no similarity among the
      isolates obtained from different animals. CONCLUSION: This experiment indicates
      that L. garvieae isolated from Seriola in Japan appears to be very different from
      the isolates obtained from other animals, and the isolates prevalent among the
      genus Seriola in Japan might be homogeneous. SIGNIFICANCE AND IMPACT OF THE
      STUDY: This study suggests that a particular genetic group that has specially
      adapted and acquired virulence toward yellowtail were prevalent among the genus
      Seriola in Japan.

PMID- 16882161
TI  - Minimizing adverse side-effects of oral bexarotene in cutaneous T-cell lymphoma:
      an expert opinion.
AB  - Bexarotene is an oral retinoid therapy that is effective for the treatment of
      early and advanced-stage cutaneous T-cell lymphoma (CTCL) in patients who have
      failed on other therapies. However, bexarotene treatment is associated with
      unavoidable side-effects, in particular hypertriglyceridaemia and hypothyroidism,
      which are manageable with adequate concomitant medications and are reversible on
      cessation of treatment. A pragmatic strategy for minimizing bexarotene-associated
      hypertriglyceridaemia and hypothyroidism is suggested, based on data from the
      studies with bexarotene in CTCL and on day-to-day experience with this agent in
      the clinical setting. The strategy anticipates that these common adverse events
      are likely to occur and recommends the early use of preventive therapy to lower
      triglycerides and elevate thyroid hormone levels in the blood, followed by
      subsequent monitoring, dose adjustment during bexarotene treatment, and titration
      of the daily bexarotene dose from 150 to 300 mg m(-2), which is optimal for most
      patients. When further information becomes available on how bexarotene interacts
      with lipid metabolism and thyroid function, the management approach suggested
      here may need to be changed.

PMID- 16882162
TI  - Autologous full-thickness skin substitute for healing chronic wounds.
AB  - BACKGROUND: Chronic wounds represent a major problem to our society. Therefore,
      advanced wound-healing strategies for the treatment of these wounds are expanding
      into the field of tissue engineering. OBJECTIVES: To develop a novel tissue
      engineered, autologous, full-thickness skin substitute of entirely human origin
      and to determine its ability to heal chronic wounds. METHODS: Skin substitutes
      (fully differentiated epidermis on fibroblast-populated human dermis) were
      constructed from 3-mm punch biopsies isolated from patients to be treated.
      Acellular allodermis was used as a dermal matrix. After a prior 5-day vacuum
      assisted closure therapy to prepare the wound bed, skin substitutes were applied
      in a simple one-step surgical procedure to 19 long-standing recalcitrant leg
      ulcers (14 patients; ulcer duration 0.5-50 years). RESULTS: The success rate in
      culturing biopsies was 97%. The skin substitute visibly resembled an autograft.
      Eleven of the 19 ulcers (size 1-10 cm2) healed within 8 weeks after a single
      application of the skin substitute. The other eight larger (60-150 cm2) and/or
      complicated ulcers healed completely (n = 5) or continued to decrease
      substantially in size (n = 3) after the 8-week follow-up period. Wound healing
      occurred by direct take of the skin substitute (n = 12) and/or stimulation of
      granulation tissue/epithelialization (n = 7). Skin substitutes were very well
      tolerated and pain relief was immediate after application. CONCLUSIONS:
      Application of this novel skin substitute provides a promising new therapy for
      healing chronic wounds resistant to conventional therapies.

PMID- 16882164
TI  - Differentiation potential of human embryonic mesenchymal stem cells for skin
      related tissue.
AB  - BACKGROUND: Mesenchymal stem cells (MSC) have the capacity to differentiate into
      cells of connective tissue lineages, including bone, fat, cartilage and muscle,
      but the differentiation of embryonic MSC into epidermal cells by mesenchymal
      epithelial transition has not been confirmed. OBJECTIVES: To determine the
      biological characteristics of human embryonic MSC (hMSC) and their potential for
      differentiation into epithelial cells. METHODS: hMSC were derived from 4-7-week
      old embryos; they were localized and isolated, then primary culture was done. The
      biological characteristics of hMSC were detected by immunohistochemical methods
      and flow cytometry. Their differentiation potential was determined by coculture
      with conditioning medium and in vivo injection. RESULTS: hMSC express the
      relative specific antigens of MSC, such as SH2, alpha-smooth actin, CD29, CD44,
      CD90 and S100. After stimulation and in vivo transplantation, hMSC possess the
      potential to differentiate into epidermal cells with the production of keratin 19
      and E-cadherin. CONCLUSIONS: hMSC derived from the early human embryo have the
      ability to transform into epidermal cells in vivo and in vitro.

PMID- 16882165
TI  - Ultraviolet (UV)A- and UVB-induced redox alterations and activation of nuclear
      factor-kappaB in human melanocytes-protective effects of alpha-tocopherol.
AB  - BACKGROUND: Despite compelling evidence that ultraviolet (UV) irradiation causes
      melanoma the knowledge concerning reaction pathways and signalling transduction
      in melanocytes is still limited. OBJECTIVES: To evaluate the protective capacity
      of alpha-tocopherol and beta-carotene during UVA and UVB irradiation of human
      melanocytes in vitro. METHODS: Primary cultures of normal human melanocytes were
      irradiated by different wavelengths within the UV spectrum (UVA 6 J cm(-2), UVB
      60 mJ cm(-2)). Redox alterations and apoptosis were studied and the protective
      potential of alpha-tocopherol and beta-carotene was evaluated. RESULTS: UVA and
      UVB irradiation decreased the intracellular concentration of reduced glutathione
      and activated the transcription factor nuclear factor (NF)-kappaB, detected as
      the increased level of the p65 subunit and translocation to the nucleus. This
      coincided with a rise in the level of gamma-glutamyl-cysteine-synthetase, the
      rate-limiting enzyme of the glutathione synthesis. UVA and UVB caused apoptotic
      cell death as detected by nuclear fragmentation and caspase activation 24 h
      postirradiation. Pretreatment with alpha-tocopherol prevented UVA- and UVB
      induced glutathione loss, NF-kappaB translocation and diminished apoptosis, but
      beta-carotene did not show a similar protective capacity. Further, exposure to
      alpha-tocopherol by itself reduced cell proliferation rate. CONCLUSIONS: UVA and
      UVB irradiation affected the intracellular redox state and increased the
      frequency of apoptosis in human melanocytes in vitro. alpha-Tocopherol might be a
      useful substance in protecting melanocytes from UV-induced damage.

PMID- 16882163
TI  - Regulation of cutaneous drug-metabolizing enzymes and cytoprotective gene
      expression by topical drugs in human skin in vivo.
AB  - BACKGROUND: Individuality in the expression and regulation of hepatic drug
      metabolizing enzymes (DMEs) and cytoprotective (CP) genes is an important
      determinant of treatment response. There is increasing evidence that many DMEs
      and CP genes are also expressed in human skin. Responses to topical drugs used to
      treat common skin diseases, such as psoriasis, are unpredictable and may
      potentially be rationalized, at least in part, by interindividual differences in
      cutaneous DME and CP gene expression. OBJECTIVES: We investigated whether three
      topical drugs [coal tar, all-trans retinoic acid (atRA) and clobetasol 17
      propionate] used in routine clinical practice modulated the expression of a
      variety of DME and CP genes [cytochrome P450s, glutathione S-transferases (GSTs)
      and drug transporters] in healthy human skin in vivo. METHODS: Healthy adult
      volunteers (n = 30) were invited to participate in the study. Each subject was
      randomly allocated to receive two of the three study chemicals and one control
      site application. Crude coal tar (n = 13), atRA (n = 14) or clobetasol 17
      propionate (n = 10) was applied under occlusion to photoprotected buttock skin
      for 96 h. A vehicle control (white soft paraffin) was also applied under the same
      conditions at an adjacent site in all subjects. Full-thickness punch biopsies (4
      mm diameter) were then taken from treated and control sites. Total RNA was
      extracted and reverse transcribed into cDNA, which was used as a template in
      subsequent real-time polymerase chain reaction analysis, where fluorescent output
      was directly proportional to input cDNA concentration. Triplicate measurements of
      skin mRNA expression were made from each sample, and the arithmetic mean values
      taken. After logarithmic transformation, the paired t-test was used to compare
      values between treated and control skin. RESULTS: Cytochrome P450s CYP1A1,
      CYP1A2, CYP1B1, CYP2C18, quinone reductase (NQO-1), GSTP1, gamma-glutamyl
      cysteine synthetase (gamma-GCS), glutathione peroxidase-1 (GPx-1), cyclooxygenase
      2 (COX-2) and haem oxygenase-1 (HO-1) were induced by coal tar; CYP26, NADPH P450
      reductase (CPR), GSTP1 and HO-1 by atRA; and CYP3A5 by clobetasol 17-propionate.
      In contrast, CYP1A1 and CYP1A2 expression was suppressed by atRA, and gamma-GCS
      and MRP1 by clobetasol 17-propionate. Marked interindividual variation in gene
      regulation by topical drugs was seen for the majority of genes examined.
      CONCLUSIONS: These data demonstrate that topical drugs can modulate DME gene
      expression in human skin in vivo and indicate that variation in the expression
      and regulation of these genes may be a determinant of individuality in response
      to topical therapies for common skin diseases.

PMID- 16882166
TI  - Several herpesviruses can reactivate in a severe drug-induced multiorgan reaction
      in the same sequential order as in graft-versus-host disease.
AB  - BACKGROUND: Drug-induced hypersensitivity syndrome (DIHS) is a severe multiorgan
      systemic reaction. Numerous studies have linked reactivation of human herpesvirus
      (HHV)-6 with the development of DIHS. Recent articles have suggested that
      reactivation of other herpesviruses besides HHV-6 might also be involved in the
      development of DIHS. On the other hand, recent studies have provided evidence for
      a role of reactivation of various herpesviruses in the development of graft
      versus-host disease (GVHD). OBJECTIVES: We attempted to determine whether
      sequential herpesvirus reactivation could be detected in four patients with
      severe DIHS, as observed in patients with GVHD, and be coincident with various
      clinical manifestations that developed after discontinuation of the causative
      drugs. METHODS: Detection and quantification of viral DNA [cytomegalovirus (CMV),
      Epstein-Barr virus (EBV), HHV-6 and HHV-7] in sequential blood samples were
      performed using real-time polymerase chain reaction assays, based on TaqMan
      technology. RESULTS: In these patients, the cascade of virus reactivation
      initiated by HHV-6 or EBV extended to EBV or HHV-7, and eventually to CMV.
      Clinical manifestations of this syndrome followed by failure of various organs
      occurring despite discontinuation of the drug were coincident with these
      herpesvirus reactivations. CONCLUSIONS: These results suggest that various
      herpesviruses can reactivate in the setting of severe drug reactions in a similar
      sequential order to that described in GVHD. The sequential reactivation of these
      herpesviruses is responsible for the development of multiorgan failure occurring
      after discontinuation of the causative drug.

PMID- 16882167
TI  - Sociodemographic factors in chronic leg ulceration.
AB  - BACKGROUND: While there is a commonly held belief that leg ulceration is
      associated with social factors, the evidence to support this is mainly anecdotal.
      OBJECTIVES: To determine deficits in sociodemographic status in patients with
      chronic leg ulceration. In a matched case-control study carried out in community
      leg ulcer clinics and participants' homes within Wandsworth Primary Care Trust,
      patients with chronic leg ulceration were compared with age- and sex-matched
      community controls drawn from general practitioner registers. Main outcome
      measures were the prevalence of social class, ethnicity, marital status, living
      status and social support. Data were analysed by conditional logistic regression.
      RESULTS: In all, 113 patients were identified and matched to controls. Patients
      had a mean age of 75 years (range 31-94), with 72 (64%) being women. The ulcer
      had been present for a median of 8 months (range 0.8-144), and 29% of patients
      had an area of ulceration >10 cm(2) (range 0.5-171.5). Being Afro-Caribbean
      increased the risk of leg ulceration eightfold (95% confidence interval, CI 1.83
      34.75; P < 0.001) compared with the white population. There was a gradient with
      social class, with patients with leg ulcers being more likely to come from social
      class IV and V (odds ratio, OR 2.82, 95% CI 1.19-6.74; P = 0.015). Never having
      married (OR 2.98, 95% CI 1.15-7.74; P = 0.025), living in rented housing (P <
      0.001) and having a mobility deficit (P < 0.001) more often occurred in the ulcer
      patients, while living with a spouse was protective (OR 0.46, 95% CI 0.21-0.99; P
      = 0.048). Patients with ulceration experienced significantly poorer social
      support than their controls for most subscales of the medical outcomes study
      social support questionnaire (all P < 0.05). CONCLUSIONS: Chronic leg ulceration
      is associated with poorer socioeconomic status, and factors which relate to
      social isolation. At present it is not possible to determine whether these
      associations are causative or are a consequence of the ulceration.

PMID- 16882168
TI  - Epidermolysis bullosa simplex in Japanese and Korean patients: genetic studies in
      19 cases.
AB  - BACKGROUND: Epidermolysis bullosa simplex (EBS) comprises a group of hereditary
      bullous diseases characterized by intraepidermal blistering caused by mutations
      in either keratin gene, KRT5 or KRT14. Significant correlation between the
      position of mutations within these proteins and the clinical severity of EBS has
      been noted. A recent report showed EBS cases in Israel had unique genetic
      features compared with European or U.S.A. associated families, which suggests
      that the ethnic and geographical features of EBS patients may be different.
      OBJECTIVES: To assess the possibility that EBS may present with certain specific
      features in Japanese and Koreans and to identify additional EBS mutations for
      genotype/phenotype correlation. METHODS: EBS was clinically diagnosed and
      confirmed by transmission electron microscopic examination of a skin biopsy.
      Mutation analysis of KRT5 and KRT14 was performed by direct sequencing in 17
      Japanese and two Korean EBS patients. RESULTS: We have identified six novel KRT5
      missense mutations (V143D, D158V, V186M, Q191P, R352S, G517D). R352S is the first
      mutation in the 2A domain. Most of these novel mutations changed amino acids that
      were evolutionarily conserved. Eight including all five mutations in EBS-Dowling
      Meara patients have been previously reported. We were unable to detect mutations
      in five sporadic EBS-Koebner patients. The proportion of mutations in KRT5 (11 of
      14; 78%) is higher than that for KRT14 mutations (3 of 14; 21%) in these Japanese
      and Korean EBS patients. CONCLUSIONS: Japanese and Korean patients with EBS
      showed very similar phenotype and genotype correlations with patients from
      Western countries. Whether the higher proportion of KRT5 mutations is a definite
      characteristic of Japanese and Korean patients with EBS or not, requires further
      research into mutations in Japanese and Korean people.

PMID- 16882169
TI  - Increased expression of the natural killer cell inhibitory receptor CD94/NKG2A
      and CD158b on circulating and lesional T cells in patients with chronic plaque
      psoriasis.
AB  - BACKGROUND: Psoriasis is a common inflammatory cutaneous disorder characterized
      by activated T-cell infiltration. T lymphocytes bearing natural killer cell
      receptors (NKRs) have been suggested to play an important role in the
      pathogenesis of psoriasis. However, the expression pattern of activating and
      inhibitory NKRs on T lymphocytes from psoriatic patients and its significance in
      psoriasis needs further study. OBJECTIVES: To investigate the pathogenesis of NKR
      expressing T cells in psoriasis. MATERIALS AND METHODS: Thirty patients with
      chronic plaque psoriasis and 20 healthy controls were enrolled in this study. The
      immunophenotypic profiles of NKRs, including CD56, CD16 (activating NKRs),
      CD158a, CD158b, CD94 and NKG2A (inhibitory NKRs), were analysed in peripheral
      blood T lymphocytes, as well as psoriatic lesional infiltrating T cells, by
      triple-fluorescence flow cytometry. RESULTS: A significant increase of inhibitory
      CD8+ CD158b+, CD4 CD8 CD158b+ and CD8+ CD94/NKG2A+ T cells was found in the
      peripheral blood of patients with psoriasis when compared with controls. Tissue
      infiltrating T lymphocytes expressing inhibitory receptors CD158b, CD94 and NKG2A
      were found in psoriatic lesions. There was a significant positive correlation
      between the increased percentage of circulating CD8+ CD94/NKG2A+ T cells and the
      Psoriasis Area and Severity Index. CONCLUSIONS: In the present study, we
      demonstrated increased proportions of particular subsets of inhibitory CD158b+
      and/or CD94/NKG2A+ T cells in patients with psoriasis. The elevation of these
      inhibitory NKR-expressing T cells was correlated with disease severity, which may
      signify the possibility of chronic antigen-driven stimulation and dysregulated
      cytokine production in the pathogenesis of psoriasis.

PMID- 16882170
TI  - Genital porokeratosis: a series of 10 patients and review of the literature.
AB  - BACKGROUND: Porokeratosis (PK) is an uncommon disorder of epidermal
      keratinization with a unique clinical appearance, unknown aetiology, and an
      unpredictable outcome. Genital PK (defined as localized PK confined to the
      genital area in this study) is extremely rare and is not well documented.
      OBJECTIVES: To evaluate the clinical manifestations, histopathology, clinical
      course and treatment response for genital PK. METHODS: We reviewed the
      clinicohistological data from 10 patients with genital PK seen at Chang Gung
      Memorial Hospital from 1990 to 2005. RESULTS: Seven patients had lesions only in
      the genital area, and three patients had genital and adjacent areas involved. All
      patients were male and the mean age at initial diagnosis was 46.0 years (range 36
      59). All but one patient presented with pruritic lesions. Three patients (30%)
      had diabetes mellitus. No malignant transformation was observed. Surgical
      excision was the most effective treatment if it could be performed. CONCLUSIONS:
      Genital PK appeared more frequently in the Asian population than in reports from
      western countries. Genital PK presented mostly as pruritic lesions in Taiwan,
      with a wide age distribution. Long-term follow-up might be needed.

PMID- 16882171
TI  - Serum levels of BAFF are increased in bullous pemphigoid but not in pemphigus
      vulgaris.
AB  - BACKGROUND: BAFF [B-cell activating factor belonging to the tumour necrosis
      factor (TNF) family] is a member of the TNF superfamily that regulates B
      lymphocyte proliferation and survival. It has been demonstrated that increased
      levels of soluble BAFF are associated with systemic autoimmunity in patients with
      systemic lupus erythematosus, rheumatoid arthritis and Sjogren's syndrome, and in
      animal models of spontaneous autoimmune diseases. However, the significance of
      circulating BAFF in autoimmune bullous diseases is unknown. OBJECTIVES: To
      examine whether BAFF levels are elevated in the autoimmune blistering diseases
      pemphigus vulgaris (PV) and bullous pemphigoid (BP). METHODS: We examined sera
      obtained from 21 patients with PV, 39 patients with BP and 22 healthy donors. We
      performed enzyme-linked immunosorbent assays for soluble BAFF and each disease
      specific antibody: antidesmoglein-3 antibody for PV and anti-BP180 antibody for
      BP. RESULTS: Significant elevations of serum BAFF levels were found in the
      patients with BP, but not with PV. There was apparently no significant
      association between the serum BAFF levels and titres of anti-BP180 antibodies in
      the patients with BP. However, serum BAFF levels tended to be more elevated in
      patients with a shorter disease duration. There was a tendency that BAFF levels
      increased before the anti-BP180 antibody levels increased at the onset of BP and
      quickly decreased in response to treatment. CONCLUSIONS: BAFF may be a useful
      marker for early activation of an autoimmune diathesis and may play a critical
      role in triggering activation of self-antigen-driven autoreactive B cells in BP.

PMID- 16882172
TI  - Sera from patients with toxic epidermal necrolysis contain autoantibodies to
      periplakin.
AB  - BACKGROUND: The pathophysiological mechanism of toxic epidermal necrolysis (TEN)
      with extensive bullae that is induced suddenly by drugs is not well understood.
      The individual patterns and distribution of the widespread mucocutaneous
      reactions of TEN often show striking similarities with those of paraneoplastic
      pemphigus (PNP), which is known to involve autoantibodies (aAbs) to members of
      the plakin family. OBJECTIVES: To investigate the existence of circulating aAbs
      to periplakin in the sera of patients with TEN. METHODS: The presence of
      circulating aAbs to periplakin was examined using immunoblotting,
      immunoabsorption and indirect immunofluorescence (IF) analyses. Recombinant
      protein expression was used to determine the interaction between periplakin and
      aAbs in the sera of patients with TEN. RESULTS: Indirect IF studies revealed
      circulating aAbs in the intercellular area in the epidermis. Interestingly, on
      rat bladder the staining pattern of the IgG deposits was similar to that observed
      in patients with PNP. Immunoblotting analysis of the epidermal extracts was used
      to identify the aAbs in the sera of patients with TEN. These contained
      circulating aAbs to a 190-kDa protein corresponding to periplakin. Recombinant
      periplakin and domains of periplakin were prepared in order to confirm the
      existence of aAbs to periplakin. Immunoblotting with these proteins demonstrated
      that the sera from patients with TEN reacted with each domain as well as with the
      full-length periplakin. CONCLUSIONS: We found that circulating aAbs in the sera
      of patients with TEN target periplakin. These aAbs might play a role in the
      pathogenesis of TEN as a humoral autoimmune mechanism.

PMID- 16882174
TI  - TNF-alpha gene 1031 T/C polymorphism in Turkish patients with Behcet's disease.
AB  - BACKGROUND: Genetic factors that predispose individuals to Behcet's disease (BD)
      are considered to play an important role in development of the disease. The
      tumour necrosis factor (TNF)-alpha gene, which is closely linked to the HLA-B51
      gene, is involved in susceptibility for BD. Recently, a polymorphism at position 
      1031 within the TNF-alpha promoter region was demonstrated to be responsible for
      susceptibility to BD in a British population. However, the functional effects of
      this polymorphism have not yet been determined. OBJECTIVES: To investigate the
      possible relation of the TNF-alpha-1031 T/C polymorphism with susceptibility to
      BD in a Turkish population and to determine the functional importance of this
      polymorphism. METHODS: Ninety-nine unrelated patients (47 women, 52 men; mean +/-
      SD age, 34.10 +/- 10.53 years) with BD and 103 ethnically matched healthy
      controls (52 males, 51 females; mean +/- SD age, 40.25 +/- 14.15) were enrolled
      in the study. For genotyping, polymerase chain reaction - restriction fragment
      length polymorphism (PCR-RFLP) analysis was employed. The functional importance
      of TNF-alpha-1031 T/C polymorphism was determined with an enzyme-linked
      immunospot (ELISPOT) assay. For this purpose, mononuclear cells obtained from BD
      patients and controls were analysed for TNF-alpha and interferon (IFN)-gamma
      production. RESULTS: A significant difference was observed between BD patients
      and controls with respect to the allele frequency of TNF-alpha-1031C [P = 0.018,
      OR = 1.83, 95% confidence interval (CI) = 1.07-3.13]. When the allele frequencies
      were analysed according to the clinical features, the T allele in patients with
      positive skin pathergy test (SPT) was significantly increased when compared with
      those of patients without these findings (P = 0.004, OR = 2.75, 95% CI = 1.3
      5.86). To demonstrate the frequency of TNF-alpha and IFN-gamma producing cells,
      mononuclear cells from four representative individuals of each genotype were used
      and the spontaneous and stimulated TNF-alpha and IFN-gamma values (spot numbers)
      were analysed. Compared with the control groups, a significant increase was
      observed in the number of cells producing TNF-alpha obtained from BD patients (P
      < 0.001). Moreover, the stimulation index for TNF-alpha [bacterial
      lipopolysaccharide (LPS) stimulated/unstimulated] was higher for the CC genotype
      (9 +/- 9.5) with respect to the other genotypes (TT; 1.3 +/- 0.3 and TC; 1.2 +/-
      0.2). While the difference in the spontaneous IFN-gamma values between groups
      were not statistically significant, the stimulated IFN-gamma values were found to
      be significantly increased in the BD group when compared with the healthy control
      group (P = 0.004). CONCLUSIONS: Our results showed that, in the Turkish
      population the TNF-alpha-1031C allele is associated with susceptibility to BD. On
      the other hand, carrying the T allele may render patients more prone to
      developing a positive skin pathergy test. In addition, ELISPOT assays revealed
      that BD patients exhibited a significantly higher number of mononuclear cells
      producing TNF-alpha, and cells obtained from patients with a CC genotype had a
      stronger response to LPS stimulation. The strong IFN-gamma response upon LPS
      stimulation in BD patients supports the previous findings that BD is a Th1 driven
      disease. These findings suggest that the TNF-alpha-1031 polymorphism may have a
      functional effect and could explain the reason for high levels of TNF-alpha
      production observed in BD patients.

PMID- 16882173
TI  - Reactivation of human herpesvirus (HHV) family members other than HHV-6 in drug
      induced hypersensitivity syndrome.
AB  - BACKGROUND: Drug-induced hypersensitivity syndrome (DIHS) is characterized by a
      severe multiorgan hypersensitivity reaction that usually appears after a 3-6-week
      exposure to certain drugs, including anticonvulsants. There are some reports
      showing that serum IgG levels often decrease at the early stage of DIHS.
      Reactivation of human herpesvirus (HHV)-6 has been reported in patients with
      DIHS, and some other DIHS patients showed reactivation of cytomegalovirus (CMV)
      or Epstein-Barr virus (EBV). OBJECTIVES: To determine whether reactivation of HHV
      6, HHV-7, CMV and/or EBV occurs in patients with DIHS. METHODS: Titres of IgG and
      IgM antibodies to HHV-6 and HHV-7 were determined using an indirect
      immunofluorescence antibody assay on admission and at various times after
      admission. Anti-CMV IgG and IgM antibody titres and anti-EBV capsid antigen IgG,
      IgA, IgM, and EBV nuclear antigen and EBV early antigen IgG titres were
      determined by enzyme immunoassay. Polymerase chain reaction (PCR) procedures for
      HHV-6, HHV-7, CMV and EBV DNAs were performed using serum samples. IgG antibody
      titres to HHV-6, HHV-7, CMV and EBV were increased after the onset in seven, six,
      seven and two of seven patients, respectively. IgG antibody titres to HHV-6 and
      HHV-7 were elevated simultaneously 21-38 days after the onset. RESULTS: IgG
      antibody titres to CMV and EBV were elevated 10-21 days after the elevation of
      HHV-6 and HHV-7 antibody titres. PCR showed that HHV-6, HHV-7, CMV and EBV DNAs
      became positive in six, five, seven and two of seven patients, respectively. HHV
      6 and HHV-7 DNAs were detected 21-35 days after the onset, and CMV DNA was
      detected 10-21 days after detection of HHV-6 and HHV-7 DNAs. CONCLUSION: The
      present study suggests that in addition to HHV-6 reactivation, reactivation of
      HHV-7, CMV and/or EBV may also occur following drug eruption in some patients
      with DIHS.

PMID- 16882175
TI  - 18F-fluorodeoxyglucose-positron emission tomography in evaluation of primary
      cutaneous lymphoma.
AB  - BACKGROUND: The diagnosis of primary cutaneous lymphoma (PCL) is currently based
      on clinical and histological findings and/or relatively invasive procedures such
      as bone marrow and fine-needle lymph node biopsies. Although computed tomography
      (CT) is a noninvasive imaging modality that is widely used for staging in
      patients with lymphoma, it cannot provide information about malignant cutaneous
      lesions. OBJECTIVES: To investigate the usefulness of (18)F-fluorodeoxyglucose
      (FDG)-positron emission tomography (PET) in the management of PCL. METHODS: We
      retrospectively analysed 31 FDG-PET studies in 19 patients with PCL [15 T-cell
      non-Hodgkin lymphoma (NHL) and four B-cell NHL]. There were 10 men and nine women
      (age range 23-84 years, mean +/- SD 54 +/- 16). Eleven FDG-PET studies were
      performed for initial staging and 20 FDG-PET studies were performed for restaging
      following therapy. Results of FDG-PET were compared with those of CT. Clinical
      parameters and/or biopsy results of lesions served as reference for the accuracy
      of PET and CT in evaluating local and metastatic lesions. RESULTS: For the
      initial staging, FDG-PET had a sensitivity of 82% for the evaluation of local
      disease and 80% for the detection of distant metastasis. The corresponding values
      for CT were 55% and 100%, respectively. For restaging of cutaneous lymphoma, FDG
      PET had a sensitivity of 86% and specificity of 92% for local recurrence/residual
      disease and a sensitivity of 100% and specificity of 100% for distant metastasis.
      The corresponding values for CT were 50% and 83% for local recurrence/residual
      disease and 100% and 67% for distant metastasis. CONCLUSIONS: FDG-PET has a
      potential value for initial staging and restaging following therapy in patients
      with PCL. FDG-PET has higher diagnostic value than CT in the detection both of
      local disease and distant metastasis.

PMID- 16882176
TI  - Optimal parameters for the treatment of leg veins using Nd:YAG lasers at 1064 nm.
AB  - BACKGROUND: The treatment of large vessels such as leg veins is successfully
      performed in clinical practice using pulsed Nd:YAG lasers. However, it is still
      unclear how laser parameters such as wavelength, fluence and pulse duration
      influence vessel destruction in leg veins. OBJECTIVES: To elucidate the governing
      parameters in selective photothermolysis of large vessels. METHODS: A recently
      developed mathematical model for photothermolysis has been adapted for the
      treatment of leg veins. The model was used to analyse the effectiveness of the
      selective photothermolysis process in laser treatment of leg veins by Nd:YAG at
      1064 nm. The efficiency of laser-induced vessel heating was defined as a ratio
      between the absorbed and delivered energy. RESULTS: The efficiency improved with
      increasing vessel diameter, in agreement with clinical findings in various
      studies. The pulse duration made a minor contribution for laser fluences of 100
      400 J cm(-2), whereas the efficiency was better for a small spot. The use of
      moderate fluences of 100-200 J cm(-2) reduced excess dermis heating and pain.
      CONCLUSIONS: We provide reference parameters for optimal treatment of leg veins
      using Nd:YAG lasers at 1064 nm. Our model predicts a maximal efficiency of a
      range of fluences (100-200 J cm(-2)) and pulse durations (10-100 ms).

PMID- 16882177
TI  - Human T-cell lymphotropic virus type 1 provirus and phylogenetic analysis in
      patients with mycosis fungoides and their family relatives.
AB  - BACKGROUND: Mycosis fungoides (MF) is a cutaneous T-cell lymphoma of unknown
      aetiology. A pathogenic role of human T-cell lymphotropic virus type 1 (HTLV-1)
      has been suggested but remains controversial. To determine whether MF is linked
      to HTLV-1. METHODS: Blood samples were collected from 60 patients, 15 family
      relatives of patients with MF (MFRs), 20 healthy controls and 10 patients with
      HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The presence
      of HTLV-1 antibodies in serum was tested by the Western blot rp21e-enhanced test.
      DNA was extracted from the blood with the Qiagen blood kit. We used 500 ng of DNA
      either in conventional HTLV-1-specific polymerase chain reaction (PCR) or in real
      time PCR using primers sk43 and sk44 together with a tax-specific fluorescent
      probe. RESULTS: In Western blot, antibodies against three to four HTLV-1 antigens
      were detected in 52% of patients with MF. All of the patients with HAM/TSP were
      positive, while only 7% of the MFRs and none of the 20 healthy controls reacted
      with HTLV-1 antigens in Western blot. One of 60 patients with MF and one of 15
      MFRs were positive in HTLV-1 PCR. These two PCR-positive samples which were
      quantified in real-time PCR showed that fewer than five in 10(6) cells were HTLV
      1 infected. We succeeded in amplifying and sequencing the 5' end of the provirus
      from the blood of the PCR-positive MFR by seminested PCR. A positive result was
      also obtained in this test. Phylogenetic tree analyses revealed a high homology
      of this sequence with other HTLV-1 sequences from the Middle East. The above PCR
      positive MFR was the brother of a PCR-negative patient with MF. CONCLUSIONS:
      These findings demonstrate that HTLV-1 is probably not the aetiological agent of
      MF. However, it may play a role in immunosuppression and in the spreading of the
      disease.

PMID- 16882178
TI  - Mycosis fungoides associated with B-cell malignancies.
AB  - BACKGROUND: The coexistence of mycosis fungoides, a peripheral T-cell lymphoma,
      and B-cell malignancies or Hodgkin's lymphoma in the same patient is unusual.
      Most descriptions are isolated case reports and case series are strikingly
      sparse. OBJECTIVES: To detect cases of mycosis fungoides associated with B-cell
      malignancies or Hodgkin's lymphoma and to analyse the characteristics of and the
      interplay between the lymphoproliferative neoplasms. METHODS: Patients with
      mycosis fungoides who had B-cell malignancies or Hodgkin's lymphoma were selected
      from among 398 patients either treated or followed up in two tertiary medical
      centres during a 7-year period. RESULTS: Eleven patients with mycosis fungoides
      and B-cell malignancy were detected (seven of non-Hodgkin's lymphoma, three of
      chronic lymphocytic leukaemia, one of multiple myeloma). No case of Hodgkin's
      lymphoma was found. In seven patients the mycosis fungoides preceded the B-cell
      malignancy whereas in four it was the B-cell malignancy which occurred first. The
      time elapsed between onset of the two malignancies ranged from 4 to 22 years
      (average: 12 years). Patients who had mycosis fungoides as the first neoplasm
      presented with earlier stages of mycosis fungoides (four of seven: IA, three of
      seven: IB) than those who had mycosis fungoides as their second neoplasm (of
      four, one: IB, one: folliculotropic, two: IIB). Among the four patients in whom
      the appearance of mycosis fungoides followed the B-cell malignancy, three had
      been treated with multiagent chemotherapy. Two patients who presented with early
      stage mycosis fungoides (IA) as the first lymphoma developed mycosis fungoides
      tumours after becoming immunosuppressed. In two patients infiltrates composed of
      both malignant T- and B-cell populations were found in a single biopsy. One
      showed two distinct populations of the malignant cells in the skin tumour, thus
      constituting a classical composite lymphoma of mycosis fungoides and chronic
      lymphocytic leukaemia, while in the other patient the two malignant populations
      of marginal B-cell lymphoma and mycosis fungoides (as evidenced by both
      phenotypic and genotypic findings) were intermingled. CONCLUSIONS: This case
      series indicates that while the coexistence of Hodgkin's lymphoma and mycosis
      fungoides is extremely rare, the association of mycosis fungoides and B-cell
      malignancies is not as rare as reflected in the literature, with non-Hodgkin's
      lymphoma constituting the most common associated B-cell malignancy. In this
      series as well as in the cases reported in the literature mycosis fungoides
      usually preceded the development of B-cell malignancies, which may be in
      accordance with previous reports of an increased risk of developing a second
      haematological neoplasm. The importance of a competent immune system for patients
      with mycosis fungoides is well demonstrated in these cases. It is suggested that
      for greater precision the criteria for diagnosis of composite lymphoma of the
      skin should include both phenotypic and genotypic features.

PMID- 16882179
TI  - Preferences for aspects of a dermatology consultation.
AB  - BACKGROUND: General practitioners with special interests (GPSIs) are increasingly
      being used to provide dermatology services in the U.K. Little is known about U.K.
      dermatology patient attitudes to proposed variations in secondary care service
      delivery or the values they attach to aspects of the care they receive.
      OBJECTIVES: To quantify preferences for different attributes of care within
      dermatology secondary care services. METHODS: Attributes of care that are
      important to dermatology patients were derived using in-depth qualitative
      interviews with 19 patients at different points in the care pathway. A discrete
      choice experiment using 'best-worst scaling' was sent by post to 119 patients
      referred to secondary care dermatology services and suitable for GPSI care who
      had agreed to participate in research. RESULTS: Four attributes were derived from
      the qualitative work: waiting, expertise, thorough care and convenience. For the
      discrete choice experiment, 99 patients returned questionnaires, 93 of which
      contained sufficient data for analysis. All attributes were found to be
      quantitatively important. The attribute of greatest importance was expertise of
      the doctor, while waiting time was of least importance. Respondents were willing
      to wait longer than the current 3 months maximum to receive care that was
      thorough, 2.1 months to see a team led by an expert and 1.3 months to attend a
      consultation that is easy to get to. CONCLUSIONS: Although the need to reduce
      outpatient waiting times is a key policy driver behind the expansion of GPSI
      services, this does not appear to be the most important issue for patients. The
      thoroughness with which the consultation is provided and the expertise of the
      clinician seen are higher priorities.

PMID- 16882181
TI  - Basal cell carcinoma: histological classification and body-site distribution.
AB  - BACKGROUND: Basal cell carcinoma (BCC) is the most common cancer worldwide in
      white-skinned populations. Recent studies suggest that BCC is not a single entity
      and that different histological subtypes show different clinical behaviour and
      might have different aetiology. OBJECTIVES: To provide information on the
      incidence of BCC by histopathological subtype and body site. METHODS: A case
      series of BCC from a prospective population-based register study collecting
      information on all excised and histologically confirmed skin cancers in
      Townsville, north Australia between 1997 and 1999. RESULTS: Age-standardized
      incidence rates for nodular BCC were 727.1 per 100 000 inhabitants per year for
      males and 411.8 for females, while rates for superficial BCC were 336.5 for males
      and 251.4 for females. Incidence rates for 'high risk' BCC were 261.3 for males,
      146.5 for females with infiltrative, and 156.7 for males and 100.2 for females
      with micronodular types. Superficial BCC occurred at a younger age, particularly
      in female patients. For all histological subtypes and both genders relative
      tumour density was highest for the face, followed by the neck. An exception was
      superficial BCC in males, where the posterior trunk was second, followed by the
      neck. CONCLUSIONS: The study found a higher rate of superficial BCC than previous
      studies from less sun-exposed countries, and a more equal distribution of
      superficial BCC on face, trunk and limbs. These results seem to blur the
      difference between intermittent and continuous sun exposure as the causative
      environmental agents. The clinical implications of 'high risk' BCC rates are
      discussed.

PMID- 16882180
TI  - The impact of psoriasis guidelines on appropriateness of referral from primary to
      secondary care: a randomized controlled trial.
AB  - BACKGROUND: Most patients with psoriasis have limited disease which can be
      managed effectively in primary care. There is a marked variation in the frequency
      of referrals between practices reflecting, in part, inadequate training of
      general practitioners (GPs) in the management of psoriasis. OBJECTIVES: To assess
      the effectiveness of guidelines and training sessions on the management of
      psoriasis in reducing inappropriate referrals from primary care. METHODS:
      Patients aged 18 years or over with psoriasis were eligible for the cluster
      randomized, randomized controlled trial if they were referred by their GP between
      9 September 2002 and 31 December 2003 to one of four hospital dermatology
      departments in Greater Manchester, North-West England. All GPs from 165 health
      centres were invited to a lecture by a local dermatologist on the diagnosis and
      management of psoriasis. Health centres in the intervention arm received
      guidelines on the management of psoriasis in primary care, developed by local
      dermatologists, supplemented by the offer of a practice-based nurse-led training
      session; those in the control arm received neither guidelines nor training
      sessions. RESULTS: Eighty-two health centres were randomized to the intervention
      arm and 83 to the control arm. Outcome data were available for 188 of the 196
      eligible patients referred during the study period. Patients in the intervention
      arm were significantly more likely to be appropriately referred in comparison
      with patients in the control arm [difference = 19.1%; odds ratio (OR) 2.47; 95%
      confidence interval (CI) 1.31-4.68; intracluster correlation coefficient (ICC) =
      0]. Only 25 (30%) health centres in the intervention arm took up the offer of
      training sessions. There was no significant difference in outcome between health
      centres in the intervention arm that received a training session and those that
      did not (OR 1.28, 95% CI 0.50-3.29, ICC = 0). CONCLUSIONS: Dissemination of
      guidelines on the management of psoriasis in primary care can significantly
      enhance the appropriateness of referral of patients to secondary care.

PMID- 16882182
TI  - Inhibition of nitric oxide and reactive oxygen species production improves the
      ability of a sunscreen to protect from sunburn, immunosuppression and
      photocarcinogenesis.
AB  - BACKGROUND: More effective strategies are required for the prevention of skin
      cancer, which is caused by ultraviolet (UV) radiation in sunlight. Sunscreens
      containing UV filters or reflectors offer some protection from sunlight.
      Pharmacologically active compounds that reduce UV damage offer considerable
      potential for improving sunscreen formulations. However, few studies have
      investigated whether the addition of such biological modifiers are an
      improvement. OBJECTIVES: In this study we supplemented a 2-ethyl hexyl
      methoxycinnamate-based sunscreen with the nitric oxide (NO) inhibitor NG
      monomethyl-L-arginine acetate, the iron chelator 2,2'-dipyridyl, which reduces
      reactive oxygen species (ROS) production, or both. This was to determine whether
      inhibition of NO, ROS, or both could improve photoprotection by a sunscreen.
      METHODS: These sunscreens were compared for photoprotection from sunburn,
      immunosuppression and skin carcinogenesis in mice. To observe additional
      photoprotection by the NO and ROS inhibitors, UV doses were used that exceeded
      the protective capacity of the sunscreen. RESULTS: The combined inhibition of
      both NO and ROS production, but neither alone, increased sunscreen protection
      from sunburn and immunosuppression. Similarly, inhibition of both NO and ROS but
      neither alone reduced tumour multiplicity and incidence, therefore improving
      sunscreen protection from photocarcinogenesis. CONCLUSIONS: Whether NO and ROS
      inhibition were independently improving sunscreen photoprotection, with both
      being required for an observable effect, or whether inhibition of an interaction
      between NO and ROS was responsible for improved photoprotection by the sunscreen
      is unknown. These studies show that supplementation of a sunscreen with
      inhibitors of NO and ROS production improves the ability of the sunscreen to
      protect from sunburn, immunosuppression and photocarcinogenesis. Such an approach
      may be useful for reducing skin cancer incidence in humans.

PMID- 16882183
TI  - Validation of a semiautomated method of minimal erythema dose testing for
      narrowband ultraviolet B phototherapy.
AB  - BACKGROUND: The most widely used method for establishing the minimal erythema
      dose (MED) before narrowband ultraviolet (UV) B phototherapy is time-consuming,
      inconvenient and may yield inconsistent results. OBJECTIVES: To assess the
      equivalence of MED assessment using a filtered xenon arc lamp UV source, a
      semiautomated MED tester, and a UV-opaque template method of MED determination
      with a panel of TL-01 311-nm UVB fluorescent tubes. Secondly, to gauge the
      current usage of MED testing, and the method used, in a large sample of U.K.
      phototherapy units. Thirdly, to assess variation in UV output of the
      semiautomated skin tester immediately after switching on to identify optimum warm
      up time. Finally, to assess reproducibility of MED testing by assessing within
      patient variability and interobserver variability of MED test results. METHODS:
      Sixty-five patients about to undergo UVB phototherapy had their MED determined
      using three different methods. Within each patient we compared the values of MED
      determined by a semiautomated Durham MED tester, a panel of narrowband UVB lamps
      with a UV-opaque template constructed by a phototherapist, and a 310-nm filtered
      xenon arc lamp with a liquid light guide. MED test results were assessed by
      clinical evaluation using a 6500 K colour temperature examination lamp. The
      output of the semiautomated MED tester was measured by spectroradiometer over a
      period of 20 min in order to identify the time to steady output. Reproducibility
      of MED testing with the semiautomated MED tester was carried out in 25 normal
      volunteers. All MEDs were assessed by at least two independent observers. A
      postal questionnaire was sent to 78 U.K. phototherapy units to assess routine
      practice concerning MED testing prior to narrowband UVB phototherapy. RESULTS:
      The semiautomated MED tester showed consistency with the panel method (r = 0.92,
      panel MED = -0.57 + 1.14 x Durham MED). The semiautomated MED tester produced a
      slightly lower MED result than the panel MED. Reproducibility tests showed high
      interobserver agreement (kappa value = 0.79), and high consistency for successive
      day testing (kappa value = 0.79). Questionnaires were returned from 67 of 78
      phototherapy units (85%) and revealed that 19 units (28%) were routinely using
      MED testing prior to UVB therapy. CONCLUSIONS: This study has shown the Durham
      MED tester to be a convenient, valid and reproducible method for determining
      patient MED values prior to narrowband UVB phototherapy when used under carefully
      controlled lighting, by experienced observers.

PMID- 16882184
TI  - Variability in the clinical pattern of cutaneous side-effects of drugs with
      systemic symptoms: does a DRESS syndrome really exist?
AB  - OBJECTIVE: To improve the definition of the various clinical patterns of patients
      with drug-induced cutaneous side-effects with systemic symptoms, and their
      possible relationships with the triggering medication, with the ultimate goal of
      helping in the identification of the causal drug in difficult situations when the
      patient is taking several drugs. METHODS: Cases of drug-induced cutaneous side
      effects associated with various systemic syndromes related to anticonvulsants
      (carbamazepine, phenytoin and phenobarbitone), minocycline, allopurinol, abacavir
      and nevirapine were collected retrospectively from the French Pharmacovigilance
      database (FPD) over a period of 15 years (1985-2000). The clinical patterns
      typical of the causative drugs were described and compared with data from the
      literature. RESULTS: Two hundred and sixteen patients with symptoms and signs
      consistent with cutaneous drug reactions with systemic symptoms were reported to
      the FPD during this period of time. Their pattern was similar to published data
      for these drugs, with fever, cutaneous eruption, hepatic abnormalities and
      eosinophilia being the most prominent but inconstant symptoms. There are clues
      suggesting that some particular lesional patterns may exist for some drugs.
      CONCLUSIONS: Although some trends emerge from these retrospective data, they
      suggest that no clear, unified outline can currently be defined for these multi
      organ drug-induced reactions. Instead, a constellation of various symptoms and
      signs were recorded, that might be sorted in different patterns according to the
      causal drug, a finding that might indeed improve accurate identification of the
      causative drug in patients receiving several principal medications at a time. A
      national prospective study systematically collecting standardized data is
      required better to define the outlines of these severe adverse drug reactions and
      to evaluate prognostic data.

PMID- 16882185
TI  - A placebo-controlled randomized study on the clinical effectiveness,
      immunohistochemical changes and protoporphyrin IX accumulation in fractionated 5
      aminolaevulinic acid-photodynamic therapy in patients with psoriasis.
AB  - BACKGROUND: Topical 5-aminolaevulinic acid (ALA)-photodynamic therapy (PDT) for
      the treatment of psoriasis has been evaluated in a few studies. In these studies
      different treatment parameters were used, there was a variable clinical response,
      and a nonhomogeneous fluorescence was seen after irradiation with Wood's light.
      OBJECTIVES: To study the clinical effectiveness, immunohistochemical changes and
      protoporphyrin IX accumulation in ALA-PDT in patients with psoriasis. Eight
      patients with stable plaque psoriasis with symmetrical involvement were included
      in the study. Two symmetrical plaques were randomly allocated to PDT either with
      10% ALA or with placebo. Irradiation consisted of 2 and 8 J cm(-2) with a dark
      interval of 2 h (Waldmann PDT 1200 L, 600-750 nm, 40 mW cm(-2)) once weekly for 4
      weeks. Before, during and after irradiation, fluorescence diagnosis was
      performed. Biopsies were taken at baseline, week 1 and week 6 for
      immunohistochemical assessment. Psoriatic plaques were clinically assessed using
      the plaque severity (sum) score. Fluorescence diagnosis was performed and
      expression of immunohistochemical markers for proliferation, differentiation and
      T-cell infiltration [Ki67, keratin 10 (K10), CD4, CD8 and CD45RO] was assessed.
      RESULTS: From week 1 up to week 6, ALA-PDT gave a significant reduction in the
      number of Ki67+ nuclei, while the K10 expression increased. After 6 weeks
      significant improvement was observed for CD8 and CD45RO. These changes were
      absent in the placebo-treated lesions. The sum scores were also significantly
      lower in the ALA-treated plaques. Heterogeneity of macroscopic fluorescence was
      observed during treatment despite keratolytic treatment. CONCLUSIONS: The present
      study shows that clinical improvement during fractionated ALA-PDT in psoriasis
      parallels histological improvement as seen in normalization of epidermal
      proliferation, differentiation and infiltration of relevant T-cell subsets.
      Optimizing the current treatment protocol may increase clinical efficacy further.

PMID- 16882186
TI  - Male New Zealand Black/KN mice: a novel model for autoimmune-induced permanent
      alopecia?
AB  - BACKGROUND: Irreversible, permanent and scarring alopecia is associated with
      several autoimmune diseases, including all autoimmune connective tissue
      disorders. The pathogenesis of autoimmune-induced permanent alopecia (APA) is
      still poorly understood, and instructive, simple mouse models for the study of
      APA are needed urgently. During the course of our studies in a well-established
      mouse model for chronic rheumatoid arthritis, the New Zealand Black/KN (NZB/KN)
      mouse, we noticed that ageing male NZB/KN mice developed spontaneous APA.
      OBJECTIVES: To study whether alopecia seen in ageing male NZB/KN mice displays
      key features of human APA and may, thus, be a useful new mouse model for
      clinically relevant APA research. METHODS: NZB/KN, the F1 hybrid of NZW/N Slc x
      NZB/KN (W/BKN F1), the F1 hybrid of NZB/KN x NZW/N Slc (BKN/W F1), and the F2
      hybrid of W/BKN F1 x W/BKN F1 mice were employed in this study, in order to check
      which strain carries the highest risk of alopecia development. Besides routine
      histology, CD3, CD4 and CD8 expression as well as immunoglobulin (Ig) G and IgM
      deposition in hair follicles were investigated by
      immunohistology/immunofluorescence. Mast cell distribution/degranulation and Ki
      67 (proliferation)/TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP
      biotin nick end labelling) (apoptosis) positive cells were also analysed.
      RESULTS: Only F2 male NZB/KN mice were prone to develop alopecia, suggesting that
      Y chromosome-associated gene(s) are involved in the pathogenesis of APA, which
      incidence rises with increasing age. The lesional alopecia skin in 12-month-old
      male NZB/KN mice showed a sharp decline in hair follicle density, thus meeting a
      key criterion of permanent alopecia. Both macroscopically and histologically, the
      alopecia seen in these mice resembled in many respects different stages of
      clinical APA, such as alopecia associated with chronic discoid lupus
      erythematosus (DLE) in humans. Lesional APA hair follicles in mice displayed
      intrafollicular and perifollicular mononuclear cell infiltrates, as well as an
      increased number of activated (degranulated) perifollicular mast cells. In the
      fully developed lesion, many CD4+ cells were seen in perifollicular locations,
      including the epithelial stem cell region (bulge), and also contained a few CD8+
      T cells. IgM deposits were found in the follicular basement membrane zone (BMZ).
      Both in the bulge and the hair matrix region of the affected anagen hair
      follicles, there were signs of massive keratinocyte apoptosis. CONCLUSIONS: Our
      currently available data suggest that male but not female NZB/KN mice may indeed
      represent a suitable mouse model for APA, with some similarities to the permanent
      alopecia seen in human DLE patients, although additional and confirmatory
      investigations are needed before this mouse strain can be accepted as a murine
      equivalent of APA in humans.

PMID- 16882187
TI  - Clinical and serological follow-up studies of endemic pemphigus foliaceus (fogo
      selvagem) in Western Parana, Brazil (2001-2002).
AB  - BACKGROUND: Fogo selvagem (FS) has been described in several regions of Brazil,
      including the Western regions of the state of Parana. In 1990, Empinotti et al.
      reported case studies of 213 patients with FS that were collected from 1976 to
      1988. The same author (J.C.E.) has observed that the frequency of cases in these
      regions of Parana has decreased. OBJECTIVES: The purpose of this study was to
      clinically and serologically evaluate a small group of the patients originally
      reported in 1990 and compare data with a group of control individuals. These
      patients were treated at the onset of the disease with systemic steroids.
      PATIENTS AND METHODS: Patients with FS, their unaffected relatives (n = 80) and
      genetically unrelated controls (n = 15) were identified during a field study from
      1 May 2001 to 30 June 2002. Sera from nine patients with FS and six normal
      controls that were collected in the 1976-1988 evaluation were available for this
      study. The sera were tested by indirect immunofluorescence, enzyme-linked
      immunosorbent assay (ELISA) and immunoprecipitation using recombinant human
      desmoglein 1 (Dsg1). RESULTS: Only 16 of the originally identified 213 patients
      with FS were found during the field studies. Thirteen of the 16 patients were in
      clinical and serological remission; 20% of normal controls (19 of 95) were
      positive in the Dsg1 ELISA. The majority of these subjects (17 of 19) were
      genetically related to FS patients. Six normal controls that were positive in the
      Dsg1 ELISA in the original survey were found to be negative or weakly positive in
      this evaluation. CONCLUSION: The reduced frequency of positive serological
      markers of disease in patients and normal controls from Western Parana, as well
      as the absence of recurrent disease in previously identified patients, suggest
      that environmental antigenic stimulation of the population at risk may have
      decreased in recent years.

PMID- 16882188
TI  - Successful treatment of multiple actinic keratoses in organ transplant patients
      with topical 5% imiquimod: a report of six cases.
AB  - BACKGROUND: Nonmelanoma skin cancer represents a significant cause of morbidity
      in organ transplant recipients (OTRs). Cutaneous malignancies, mainly invasive
      squamous cell carcinoma and its precursor actinic keratosis (AK), appear
      approximately 5-10 years after organ transplantation. Impaired wound healing and
      high recurrence rates in immunocompromised patients treated with destructive
      therapies such as cryosurgery or topical 5-fluorouracil represent frequently
      known complications. OBJECTIVES: To evaluate the safety and efficacy of imiqimod
      5% in the treatment of AKs in OTRs. METHODS: Six OTRs (two kidney, two heart, one
      lung and one liver) with extensive AKs were treated with imiquimod 5% cream two
      to three times weekly in an open-label uncontrolled, nonrandomized pilot study.
      RESULTS: In five of six patients treated with imiquimod 5% cream all AK lesions
      were cleared after 12-16 weeks. One patient showed partial response. Local
      adverse events at the site of application included erythema, oedema and mild
      erosion. No wound infection or scarring was observed in any of these patients.
      All graft-related laboratory parameters were stable during and after treatment.
      Immunosuppressive therapy remained unchanged throughout the treatment.
      CONCLUSIONS: These results suggest that imiquimod 5% cream may be useful for the
      local treatment of precancerous AK lesions in OTRs.

PMID- 16882189
TI  - Dramatic improvement of psoriatic erythroderma after acute hepatitis: analysis of
      cytokine synthesis capability in peripheral blood T cells.
AB  - We report a patient with psoriasis and hepatitis C virus infection who initially
      presented with psoriatic erythroderma and eventually showed complete clearance of
      psoriatic lesions following acute hepatitis induced by etretinate treatment.
      Cytokine synthesis capabilities in peripheral blood T cells obtained at different
      stages were evaluated in this patient. A dramatic increase in the frequency of
      interferon-gamma-producing CD8+ T cells in peripheral blood was observed during
      the erythrodermic stage. In contrast, the frequencies of interleukin (IL)-4- and
      IL-13-producing CD4+ T and CD8+ T cells were remarkably high at the resolution
      stage. These results clearly indicate that a shift towards type 2 cytokine
      predominance contributes to the resolution of severe psoriasis.

PMID- 16882190
TI  - Eosinophilic ulcer of the oral mucosa: another histological simulator of CD30+
      lymphoproliferative disorders.
AB  - Eosinophilic ulcer of the oral mucosa (EUOM), also known as traumatic ulcerative
      granuloma with stromal eosinophilia or Riga-Fede disease, is an uncommon benign
      self-limited lesion poorly described in the dermatological literature. It
      probably includes a spectrum of related disorders presenting as an ulcer with
      elevated indurated borders affecting the tongue, oral mucosa or lip.
      Histopathological findings are characteristic and consist of eosinophil-rich
      mixed infiltrates accompanied by a population of large mononuclear cells whose
      origins have been a matter of debate. Immunohistochemical studies of these cells
      have suggested a myofibroblastic or histiocytic origin. We present a 93-year-old
      woman with two episodes of self-healing ulcers on the upper lip and on the
      lingual mucosa, respectively. Histopathological findings on both biopsies were
      consistent with EUOM and showed the presence of large atypical CD30+ lymphocytes.
      Some recent reports have also shown positivity for the CD30 antigen, raising the
      possibility that a subset of EUOM could be included within the spectrum of CD30+
      lymphoproliferative disorders. This finding most likely suggests that EUOM can
      represent another histological simulator of CD30+ lymphoproliferative disorders.

PMID- 16882191
TI  - Acquired erythropoietic protoporphyria as a result of myelodysplasia causing loss
      of chromosome 18.
AB  - We report a patient aged 73 years, who developed erythropoietic protoporphyria
      with typical photosensitivity, at the same time as she was diagnosed as having
      myelodysplastic syndrome. The myelodysplastic clone in her bone marrow completely
      lacked one of the two copies of chromosome 18. As chromosome 18 is the locus of
      the ferrochelatase gene, we postulate that this chromosomal deletion led to
      reduced synthesis of the enzyme in the bone marrow clone, so causing the
      porphyria. The nature of the remaining ferrochelatase allele was examined by
      polymorphism analysis and we discuss the insights that this patient's genotype
      may reveal about the pathogenesis of porphyria in myelodysplasia.

PMID- 16882192
TI  - A novel mutation in the ARS (component B) gene encoding SLURP-1 in a Turkish
      family with mal de Meleda.

PMID- 16882193
TI  - New compound heterozygous mutations in a Chinese family with lipoid proteinosis.

PMID- 16882194
TI  - Two frameshift mutations of the double-stranded RNA-specific adenosine deaminase
      gene in Chinese pedigrees with dyschromatosis symmetrica hereditaria.

PMID- 16882195
TI  - Erlotinib associated with rosacea-like folliculitis and Malassezia sympodialis.

PMID- 16882196
TI  - Linear IgA disease presenting as prurigo nodularis.

PMID- 16882197
TI  - Musculoskeletal and myotoxic side-effects in a patient treated for psoriasis.

PMID- 16882198
TI  - Validation of the 'polymorphic light eruption severity index'.

PMID- 16882199
TI  - Small cell variant of CD30+ primary cutaneous T-cell lymphoma with
      epidermotropism that completely regressed after incisional skin biopsy.

PMID- 16882200
TI  - Topical glycopyrrolate should not be overlooked in treatment of focal
      hyperhidrosis.

PMID- 16882201
TI  - No evidence for therapeutic effect of topical ciclosporin in oral lichen planus.

PMID- 16882203
TI  - Complete remission of multiple satellite and in-transit melanoma metastases after
      sequential treatment with isolated limb perfusion and topical imiquimod.

PMID- 16882204
TI  - Systemic illness with skin eruption, fever and positive lymphocyte transformation
      test in a patient on irbesartan.

PMID- 16882205
TI  - Imatinib mesilate inhibits melanogenesis in vitro.

PMID- 16882206
TI  - Cutaneous, perivulvar and perianal ulcerations induced by nicorandil.

PMID- 16882207
TI  - Generalized pustular psoriasis complicated by acute respiratory distress
      syndrome.

PMID- 16882211
TI  - Proper assessment of the JFK assassination bullet lead evidence from
      metallurgical and statistical perspectives.
AB  - The bullet evidence in the JFK assassination investigation was reexamined from
      metallurgical and statistical standpoints. The questioned specimens are comprised
      of soft lead, possibly from full-metal-jacketed Mannlicher-Carcano (MC), 6.5-mm
      ammunition. During lead refining, contaminant elements are removed to specified
      levels for a desired alloy or composition. Microsegregation of trace and minor
      elements during lead casting and processing can account for the experimental
      variabilities measured in various evidentiary and comparison samples by
      laboratory analysts. Thus, elevated concentrations of antimony and copper at
      crystallographic grain boundaries, the widely varying sizes of grains in MC
      bullet lead, and the 5-60 mg bullet samples analyzed for assassination
      intelligence effectively resulted in operational sampling error for the analyses.
      This deficiency was not considered in the original data interpretation and
      resulted in an invalid conclusion in favor of the single-bullet theory of the
      assassination. Alternate statistical calculations, based on the historic
      analytical data, incorporating weighted averaging and propagation of experimental
      uncertainties also considerably weaken support for the single-bullet theory. In
      effect, this assessment of the material composition of the lead specimens from
      the assassination concludes that the extant evidence is consistent with any
      number between two and five rounds fired in Dealey Plaza during the shooting.

PMID- 16882212
TI  - Evaluating the accuracy and precision of cranial morphological traits for sex
      determination.
AB  - Sex determination is a key analysis that forensic anthropologists perform in
      order to construct a biological profile of human remains. The techniques used in
      forensic investigations must meet the Mohan or Daubert criteria, for
      admissibility in a court of law. In this study, the precision and accuracy of 21
      morphological characteristics of the skull were tested on a modern sample of 50
      adult crania of European White ancestry. The following craniofacial features are
      identified as high-quality traits, defined by intraobserver error <or=10% and
      accuracy >or=80%: mastoid size, supraorbital ridge size, general size and
      architecture, rugosity of the zygomatic extension, size and shape of the nasal
      aperture, and gonial angle. Ninety-six percent accuracy and 92% precision were
      achieved using 20 traits in combination. Fisher's exact probability tests
      revealed no significant differences (p=0.05) in the levels of precision or
      accuracy between age categories. Sex-related bias in accuracy was found for the
      following cranial features: ramus symphysis (p=0.009), zygomatic extension
      (p=0.0016), and occipital markings (p=0.0013). These traits demonstrated a
      greater tendency to be scored male than female.

PMID- 16882213
TI  - Beyond the sphere of the English facial approximation literature: ramifications
      of German papers on western method concepts.
AB  - In the English literature, facial approximation methods have been commonly
      classified into three types: "Russian,""American," or "Combination." These
      categorizations are based on the protocols used, for example, whether methods use
      average soft-tissue depths (American methods) or require face muscle construction
      (Russian methods). However, literature searches outside the usual realm of
      English publications reveal key papers that demonstrate that the Russian category
      above has been founded on distorted views. In reality, Russian methods are based
      on limited face muscle construction, with heavy reliance on modified average soft
      tissue depths. A closer inspection of the American method also reveals
      inconsistencies with the recognized classification scheme. This investigation
      thus demonstrates that all major methods of facial approximation depend on both
      face anatomy and average soft-tissue depths, rendering common method
      classification schemes redundant. The best way forward appears to be for
      practitioners to describe the methods they use (including the weight each one
      gives to average soft-tissue depths and deep face tissue construction) without
      placing them in any categorical classificatory group or giving them an ambiguous
      name. The state of this situation may need to be reviewed in the future in light
      of new research results and paradigms.

PMID- 16882214
TI  - Rapid and high-throughput forensic short tandem repeat typing using a 96-lane
      microfabricated capillary array electrophoresis microdevice.
AB  - A 96-channel microfabricated capillary array electrophoresis (muCAE) device was
      evaluated for forensic short tandem repeat (STR) typing using PowerPlex 16 and
      AmpFlSTR Profiler Plus multiplex PCR systems. The high-throughput muCAE system
      produced high-speed <30-min parallel sample separations with single-base
      resolution. Forty-eight previously analyzed single-source samples were accurately
      typed, as confirmed on an ABI Prism 310 and/or the Hitachi FMBIO II. Minor
      alleles in 3:1 mixture samples containing female and male DNA were reliably typed
      as well. The instrument produced full profiles from sample DNA down to 0.17 ng, a
      threshold similar to that found for the ABI 310. Seventeen nonprobative samples
      from various evidentiary biological stains were also correctly typed. The
      successful application of the muCAE device to actual forensic STR typing samples
      is a significant step toward the development of a completely integrated STR
      analysis microdevice.

PMID- 16882216
TI  - Development of a human-specific real-time PCR assay for the simultaneous
      quantitation of total genomic and male DNA.
AB  - A duplex real-time quantitative PCR assay was developed for forensic DNA
      analysis, which provides simultaneous quantitation of total genomic human DNA and
      human male DNA. The assay utilizes two spectrally resolved fluorogenic probes in
      a 5' nuclease (TaqMantrade mark) assay. Within the range of organisms empirically
      tested and based upon theoretical specificity using National Center for
      Biotechnology Information GenBank sequences, primer and probe sequences were
      shown to be human specific, and the Y-chromosome probe, male-specific. A mixture
      challenge study resulted in accurate quantitation of 25 pg male DNA in a mixture
      of up to 1:5000 (male:female DNA). Additional experimental results include
      comparisons with the slot blot method and commercial real-time PCR kits. The
      assay developed addresses the shortcomings of the traditional slot blot method as
      well as the commercial real-time PCR kits. This method is shown to be specific,
      relatively simple, rapid, has low limits of detection, and consumes limited
      sample in addition to reporting both the male and total genomic DNA
      concentrations present.

PMID- 16882215
TI  - Laser microdissection separation of pure spermatozoa from epithelial cells for
      short tandem repeat analysis.
AB  - Short tandem repeat (STR) analysis is a valuable tool in identifying the source
      of biological stains, particularly from the investigation of sexual assault
      crimes. Difficulties in analysis arise primarily in the interpretation of mixed
      genotypes when cell separation of the sexual assailant's sperm from the victim's
      cells is incomplete. The forensic community continues to seek improvements in
      cell separation methods from mixtures for DNA typing. The feasibility of applying
      laser microdissection (LMD) technology to precisely separate sexual assault cell
      mixtures by visual inspection coupled with laser dissection was assessed through
      three experiments. First, various histological stains were evaluated for use with
      LMD and DNA analysis. Second, different DNA isolation methods were evaluated on
      LMD-collected cells. Finally, STR analysis was performed on LMD-separated sperm
      cells from mixtures of semen and female buccal epithelial cells. The results
      indicated (a) hematoxylin/eosin staining performed best in its ability to
      differentiate sperm and epithelial cells while exhibiting the least negative
      effect on further downstream analysis; (b) both QIAamp and Lyse-N-Go methods were
      useful for recovery of DNA from LMD-collected sperm cells; and (c) LMD separation
      provided clear STR profiles of the male donor with the absence of any additional
      alleles from the female donor. This report describes an efficient, low
      manipulation LMD method for the efficient separation of spermatozoa from two
      donor sperm/epithelial cell mixtures.

PMID- 16882217
TI  - Relative degradation of nuclear and mitochondrial DNA: an experimental approach.
AB  - Single copy nuclear loci often cannot be amplified from degraded remains,
      necessitating the analysis of mitochondrial DNA (mtDNA). The success in analyzing
      mtDNA is generally thought to result from its higher copy number in the cell;
      however, other factors, such as cellular location or molecular features, may be
      equally or more important in the superior preservation of mtDNA. To explore and
      compare mtDNA and nuclear DNA degradation, mouse tissues (muscle, liver, and
      brain) were allowed to degrade at different temperatures, and the relative
      degradation of a mitochondrial gene, a single copy nuclear gene, and a multi-copy
      nuclear gene was assayed using real-time polymerase chain reaction. The tissues
      were also homogenized, allowing the three loci to degrade in the same cellular
      environment. Gene copy number and cellular location both influence DNA recovery.
      In some instances, multi-copy loci could be recovered when the single copy locus
      could not; however, the pattern of relative DNA degradation changed between whole
      and homogenized tissues. The overall results indicate that DNA degradation is
      influenced by multiple factors-including cellular location, chromatin structure,
      and transcriptional activity-factors that could be used to exploit loci for more
      robust forensic analysis from degraded biological material.

PMID- 16882218
TI  - High-performance liquid chromatography-ultraviolet-visible spectroscopy
      electrospray ionization mass spectrometry method for acrylic and polyester
      forensic fiber dye analysis.
AB  - A critical point of comparison between a fiber collected from a crime scene and a
      fiber from a known source is the color. Fiber dye analysis using thin-layer
      chromatography or ultraviolet (UV)-visible (Vis) microspectrophotometry provides
      useful, although limited, data for comparison. High-performance liquid
      chromatography-electrospray ionization mass spectrometry (LC/MS) overcomes these
      limitations by integrating chromatography, ultraviolet-visible spectroscopy, and
      mass spectrometry into a single instrument. In order to evaluate the
      applicability of the LC/MS to forensic fiber dye analysis, a multi-stage
      chromatographic method using acidified water and acidified acetonitrile was
      developed that separated and identified a mixture of 15 basic and 13 disperse dye
      standards. The LC/MS also detected and analyzed dyes extracted from individual
      0.5 cm acrylic and polyester fibers, demonstrating its applicability to this type
      of analysis. With regard to the analysis of disperse dyes in polyester fibers,
      the replacement of pyridine with acetonitrile in the extraction system allowed
      direct injection of the extracts into the LC/MS. The advantage of the LC/MS over
      other instrumental methods of textile dye analysis is demonstrated by the
      analysis and differentiation of three black acrylic fibers: two fibers had
      similar UV-Vis spectra but were differentiated with chromatography and two had
      similar UV-Vis spectra and chromatograms but were differentiated using the mass
      spectrometer.

PMID- 16882219
TI  - Performance evaluation of the Scent Transfer Unit (STU-100) for organic compound
      collection and release.
AB  - The Scent Transfer Unit (STU-100) is a portable vacuum that uses airflow through
      a sterile gauze pad to capture a volatiles profile over evidentiary items for
      subsequent canine presentation to assist law enforcement personnel. This device
      was evaluated to determine its ability to trap and release organic compounds at
      ambient temperature under controlled laboratory conditions. Gas chromatography
      mass spectrometry (GC-MS) analyses using a five-component volatiles mixture in
      methanol injected directly into a capture pad indicated that compound release
      could be detected initially and 3 days after the time of collection.
      Additionally, 15 compounds of a 39-component toxic organic gaseous mixture (10
      1000 parts per billion by volume [p.p.b.(v)]) were trapped, released, and
      detected in the headspace of a volatiles capture pad after being exposed to this
      mixture using the STU-100 with analysis via GC-MS. Component release efficiencies
      at ambient temperature varied with the analyte; however, typical values of c. 10%
      were obtained. Desorption at elevated temperatures of reported human odor/scent
      chemicals and colognes trapped by the STU-100 pads was measured and indicated
      that the STU-100 has a significant trapping efficiency at ambient temperature.
      Multivariate statistical analysis of subsequent mass spectral patterns was also
      performed.

PMID- 16882220
TI  - The application of ultraviolet irradiation to exogenous sources of DNA in
      plasticware and water for the amplification of low copy number DNA.
AB  - Using high sensitivity forensic STR polymerase chain reaction (PCR) typing
      procedures, we have found low concentrations of DNA contamination in plasticware
      and water assumed to be sterile, which is not detected by standard DNA
      procedures. One technique commonly used to eliminate the presence of DNA is
      ultraviolet (UV) irradiation; we optimized such a protocol used in the treatment
      of water, tubes, plates, and tips for low copy number DNA (LCN) amplification. UV
      light from a Stratalinker((R)) 2400 was administered to 0.2, 1.5 mL tubes, and
      PCR plates contaminated with up to 500 pg of DNA. They were subsequently
      quantified with an ALU-based real-time PCR method using the Rotorgene 3000.
      Overall, there was a decrease in concentration of DNA recovered as the duration
      of treatment increased. Nonetheless, following 45 min of irradiating a PCR plate
      with 500 pg of DNA, nearly 6 pg were still detected. However, when the plate was
      raised within an inch of the UV source, less than 0.2 pg of DNA was detected.
      Additionally, lining the area around the samples with aluminum foil further
      reduced the amount of time necessary for irradiation, as only 30 min eliminated
      the presence DNA in the raised PCR plate. Similar experiments were conducted
      using tubes filled with a solution of DNA and water in equivalent concentrations
      for 50, 15, and 1.5 mL tubes with comparative results. It is plausible that the
      aluminum foil increased the amount of reflection in the area thereby enhancing
      penetration of UV rays through the walls of the plasticware. This protocol was
      tested for the possibility of inhibitors produced from irradiation of plastic
      tubes. As our protocols require less irradiation time than previous studies, PCR
      sensitivity was not affected. Moreover, the lifespan of the UV lamps was
      extended. Our findings demonstrate that this method is useful as an additional
      precautionary measure to prevent amplification of extraneous DNA from plasticware
      and water without compromising the sensitivity of LCN DNA amplifications.

PMID- 16882221
TI  - Evaluation of real-time PCR amplification efficiencies to detect PCR inhibitors.
AB  - Real-time PCR analysis is a sensitive template DNA quantitation strategy that has
      recently gained considerable attention in the forensic community. However, the
      utility of real-time PCR methods extends beyond quantitation and allows for
      simultaneous evaluation of template DNA extraction quality. This study presents a
      computational method that allows analysts to identify problematic samples with
      statistical reliability by comparing the amplification efficiencies of unknown
      template DNA samples with clean standards. In this study, assays with varying
      concentrations of tannic acid are used to evaluate and adjust sample-specific
      amplification efficiency calculation methods in order to optimize their inhibitor
      detection capabilities. Kinetic outlier detection and prediction boundaries are
      calculated to identify amplification efficiency outliers. Sample-specific
      amplification efficiencies calculated over a four-cycle interval starting at the
      threshold cycle can be used to detect reliably the presence of 0.4 ng of tannic
      acid in a 25 microL PCR reaction. This approach provides analysts with a precise
      measure of inhibition severity when template samples are compromised. Early
      detection of problematic samples allows analysts the opportunity to consider
      inhibitor mitigation strategies prior to genotype or DNA sequence analysis,
      thereby facilitating sample processing in high-throughput forensic operations.

PMID- 16882222
TI  - A simple and inexpensive molecular method for sexing and identification of the
      forensic samples of elephant origin.
AB  - The population of the Asian elephant is being dramatically reduced due to
      poaching of the ivory from the male. As poaching occurs in remote forests, it
      often takes weeks or longer for it to be discovered and it is therefore often
      very difficult to determine the sex of the decomposed body. Data suggest that in
      the recent past, over 2000 male elephants have been poached in South India. We
      have developed a technique based on molecular markers to determine that the
      carcass is an elephant and that it is a male. Using DNA sequence information from
      Genbank, we have developed two primer pairs: one for the mitochondrial DNA
      (mtDNA) and the other for the sex-determining region of Y chromosome (SRY) gene
      of the Indian elephant. After PCR amplification of known elephant DNA, we found
      that the mtDNA was common in both males and females, whereas the SRY-specific
      amplicon was observed only in the male.

PMID- 16882223
TI  - Chemical composition and structure of the microcrystals formed between silver(I)
      and gamma-hydroxybutyric acid and gamma-hydroxyvaleric acid.
AB  - This study examined microcrystals formed by silver with gamma-hydroxybutyric acid
      (GHB) and gamma-hydroxyvaleric acid (GHV), the five-carbon analog of GHB, in the
      presence of silver, copper, and lanthanide nitrates. Distinct microcrystals
      formed with silver (+1) and lanthanum (+3) ions but not with the copper (+2)
      ions. The crystals formed with GHB were distinctly different than those formed
      with GHV and in all cases, the drug microcrystals were easily distinguishable
      from reagent crystals. X-ray diffraction analysis provided definitive structure
      for the microcrystals. The morphological differences between the silver-GHB and
      silver-GHV crystals were characterized using simple measurements such as size and
      angles provided by image recognition software. The utility of the test for
      casework was demonstrated using spiked beverage samples.

PMID- 16882224
TI  - A method for enhancing gunshot residue patterns on dark and multicolored fabrics
      compared with the modified Griess test.
AB  - In using infrared or infrared-enhanced photography to examine gunshot residue
      (GSR) on dark-colored clothing, the GSR particles are microscopically examined
      directly on the fabric followed by the modified Griess test (MGT) for nitrites.
      In conducting the MGT, the GSR is transferred to treated photographic paper for
      visualization. A positive reaction yields an orange color on specially treated
      photographic paper. The examiner also evaluates the size of the powder pattern
      based on the distribution of nitrite reaction sites or density. A false-positive
      reaction can occur using the MGT due to contaminants or dyes that produce an
      orange cloud reaction as well. A method for enhancing visualization of the
      pattern produced by burned and partially unburned powder is by treatment of the
      fabric with a solution of sodium hypochlorite. In order to evaluate the results
      of sodium hypochlorite treatment for GSR visualization, the MGT was used as a
      reference pattern. Enhancing GSR patterns on dark or multicolored clothing was
      performed by treating the fabric with an application of 5.25% solution of sodium
      hypochlorite. Bleaching the dyes in the fabric enhances visualization of the GSR
      pattern by eliminating the background color. Some dyes are not affected by sodium
      hypochlorite; therefore, bleaching may not enhance the GSR patterns in some
      fabrics. Sodium hypochlorite provides the investigator with a method for
      enhancing GSR patterns directly on the fabric. However, this study is not
      intended to act as a substitute for the MGT or Sodium Rhodizonate test.

PMID- 16882225
TI  - Fast gas chromatography of explosive compounds using a pulsed-discharge electron
      capture detector.
AB  - The detection of a mixture of nine explosive compounds, including nitrate esters,
      nitroaromatics, and a nitramine in less than 140 sec is described. The new method
      employs a commercially available pulsed-discharge electron capture detector
      (PDECD) coupled with a microbore capillary gas chromatography (GC) column in a
      standard GC oven to achieve on-column detection limits between 5 and 72 fg for
      the nine explosives studied. The PDECD has the benefit that it uses a pulsed
      plasma to generate the standing electron current instead of a radioactive source.
      The fast separation time limits on-column degradation of the thermally labile
      compounds and decreases the peak widths, which results in larger peak intensities
      and a concomitant improvement in detection limits. The combination of short
      analysis time and low detection limits make this method a potential candidate for
      screening large numbers of samples that have been prepared using techniques such
      as liquid-liquid extraction or solid-phase microextraction.

PMID- 16882226
TI  - Evaluation and comparison of the electrostatic dust print lifter and the
      electrostatic detection apparatus on the development of footwear impressions on
      paper.
AB  - The Electrostatic Dust Print Lifter (EDPL) and the Electrostatic Detection
      Apparatus(2) (ESDA(2)) were compared to determine if both processes could be used
      to develop footwear impressions of the same or similar quality and in what order
      they should be used to develop the highest quality footwear impression. The
      sensitivity of each technique was also evaluated. The quality of the footwear
      impressions developed was determined by comparing 25 individual characteristics
      present on the known shoe to the footwear impressions developed using each
      technique. The footwear impressions were made by stepping on paper placed over
      several different surfaces, which included: linoleum, industrial Berber carpet,
      nylon carpet placed over a (3/8)-in. pad, ceramic tile, cardboard, 1-in. foam, 4
      in. foam, cement, asphalt, grass, and mulch. Each of the papers placed on these
      surfaces was developed using the EDPL before the ESDA(2) and vice versa. The
      sensitivity test for the ESDA(2) was conducted by processing 10 sheets of stacked
      paper that were stepped on with the known shoe, beginning with the top sheet. The
      sensitivity test for the EDPL was conducted by processing 10 sheets of paper
      stepped on with the known shoe in succession. This study determined the footwear
      impressions developed using the EDPL were of better comparative value than
      impressions developed with the ESDA(2). On average, 72.4% of the individual
      characteristics from the known impression were identified on images developed
      when the EDPL was used first compared with an average of 38.9% when the ESDA(2)
      was used first. Therefore, if only one technique is used, the EDPL should be
      chosen. The sensitivity test determined the ESDA(2) develops high-quality
      footwear impressions on only the top sheet of paper. No footwear impressions were
      developed on any sheets under the top sheet of paper. The sensitivity test also
      determined the EDPL results increase in quality as the amount of dust residue
      decreases on the surface.

PMID- 16882227
TI  - The indirect detection of bleach (sodium hypochlorite) in beverages as evidence
      of product tampering.
AB  - Bleach (sodium hypochlorite) has been identified as the adulterant in a
      relatively large number of product tamperings that have been investigated by the
      Forensic Chemistry Center (FCC) of the U.S. Food and Drug Administration. In this
      work, household bleach was added to 23 different beverages at each of three
      levels. The impact of sodium hypochlorite on these beverages over a 13-day study
      period was evaluated using the following techniques: diphenylamine spot test for
      oxidizing agents, potassium iodide-starch test paper for oxidizing agents, pH,
      iodometric titration for quantitating hypochlorite, ion chromatography for
      chloride and chlorate quantitation, automated headspace sampling with gas
      chromatography-flame ionization detection (GC-FID) for determination of
      chloroform, and visual and organoleptic observations. This study has shown that
      hypochlorite is fragile when added to most common beverages and typically breaks
      down either partially or completely over time. In cases where a beverage is
      suspected of being adulterated with bleach but tests for hypochlorite are
      negative, it is still possible to characterize the product to demonstrate that
      the results are consistent with the addition of bleach. An adulterated product
      will give a positive test for oxidizing agents using the diphenylamine spot test.
      It is likely that the pH of the adulterated product will be higher than a control
      of that product. Ion chromatographic analysis shows elevated chloride and
      chlorate as compared with a control. And, chloroform may also be detected by GC
      FID especially if the beverage that was adulterated contains citric acid.

PMID- 16882228
TI  - Potential and pitfalls in establishing the provenance of Earth-related samples in
      forensic investigations.
AB  - Earth scientists are often asked to establish or constrain the likely provenance
      of very small quantities of earth-related material as part of a forensic
      investigation. We tested the independent and collective interpretations of four
      experts with differing analytical skills in the prediction of sample provenance
      for three samples from different environmental settings. The methods used were X
      ray diffraction, scanning electron microscopy, the assessment of pollen
      assemblages, and structural characterization of organic matter at the molecular
      level. Independent interpretations were less accurate than those where multiple
      techniques were combined. Collective interpretation was very effective in the
      assessment of provenance for two of the three sites where the mineralogy and
      plant communities were distinctive. At the other site, although the mineralogical
      analysis correctly identified the Triassic mudstone soil parent material,
      Carboniferous spores from domestic coal were initially interpreted as deriving
      directly from bedrock. Such an interpretation could be a common pitfall owing to
      anthropogenic redistribution of material such as coal.

PMID- 16882229
TI  - A comparison of animal jaws and bite mark patterns.
AB  - The purpose of this study was to compare the jaw shapes and bite mark patterns of
      wild and domestic animals to assist investigators in their analysis of animal
      bite marks. The analyses were made on 12 species in the Order Carnivora housed in
      the Mammalian Collection at the Field Museum of Natural History in Chicago,
      Illinois. In addition to metric analysis, one skull from each species was
      photographed as a representative sample with an ABFO No. 2 scale in place. Bite
      patterns of the maxillary and mandibular dentition were documented using foamed
      polystyrene exemplars, which were also photographed. A total of 486 specimens
      were examined to analyze the jaw and bite mark patterns. A modified technique for
      measuring intercanine distances was developed to more accurately reflect the
      characteristics seen in animal bite marks. In it, three separate areas were
      measured on the canines, rather than just the cusp tip. This was to maximize the
      amount of information acquired from each skull, specifically to accommodate
      variances in the depth of bite injuries.

PMID- 16882230
TI  - Reliability in age determination by pulp/tooth ratio in upper canines in skeletal
      remains.
AB  - Estimation of age of skeletal remains is one of the most complex questions for
      anthropologists. The most common macroscopic methods are based on dental wear and
      histological evaluation of bone remodeling. These methods are often qualitative,
      require great technical expertise, and have proved inexact in the estimation of
      ages over 50 years. Certain dental methods investigate the apposition of
      secondary dentine, in the study of tooth cross-sections, and X-rays to study
      width, height, and pulp area. The primary author previously proposed a method of
      estimating the age of a living person based on the pulp/tooth ratio (PTR) method
      in the upper canines. The aim of the present study is to verify whether the PTR
      method can also be used to estimate the age at death of skeletal remains. This
      paper investigates the study of historical samples of known age as a means to
      validate the proposed method.

PMID- 16882231
TI  - Detection and quantification of the age-related point mutation A189G in the human
      mitochondrial DNA.
AB  - Mutation analysis in the mitochondrial DNA (mtDNA) control region is widely used
      in population genetic studies as well as in forensic medicine. Among the
      difficulties linked to the mtDNA analysis, one can find the detection of
      heteroplasmy, which can be inherited or somatic. Recently, age-related point
      mutation A189G was described in mtDNA and shown to accumulate with age in
      muscles. We carried out the detection of this 189 heteroplasmic point mutation
      using three technologies: automated DNA sequencing, Southern blot hybridization
      using a digoxigenin-labeled oligonucleotide probe, and peptide nucleic acid
      (PNA)/real-time PCR combined method on different biological samples. Our results
      give additional information on the increase in mutation frequency with age in
      muscle tissue and revealed that the PNA/real-time PCR is a largely more sensitive
      method than DNA sequencing for heteroplasmy detection. These investigations could
      be of interest in the detection and interpretation of mtDNA heteroplasmy in
      anthropological and forensic studies.

PMID- 16882232
TI  - Adolescent and young adult suicide: a 10-year retrospective review of Kentucky
      Medical Examiner cases.
AB  - The compilation of all suicidal causes of death attained the third highest
      ranking of mortality between the ages of 15 and 24 following unintentional deaths
      and homicide in the United States, accounting for approximately 4000 deaths in
      2002. A variety of biopsychosocial factors may contribute to adolescent suicidal
      behavior, including psychiatric disorders, risk-taking behaviors, and lack of a
      cohesive family unit. The authors conducted a 10-year (1993-2002) retrospective
      review of 108 Medical Examiner cases of suicide ages 11-17 and 358 cases ages 18
      24 in Kentucky, which represents two thirds of the Coroner cases in the state.
      The majority of victims were male and Caucasian. The major causes of death were
      the same for the two age groups, specifically, firearm injury (72.2% and 70.7%),
      hanging (22.2% and 18.7%), and drug intoxication (2.8% and 5.3%). An integrated
      Coroner-Medical Examiner system profits in the public health arena by providing
      collaborative research data for policy decisions. The prevalence of youth suicide
      by firearm should prompt further discussion regarding ways to better identify
      high-risk adolescents and young adults and restrict pediatric access to unsecured
      household firearms.

PMID- 16882233
TI  - Cerebral hypoxia and ischemia: the forensic point of view: a review.
AB  - In cases with suspected brain anoxia/ischemia and hypoxia/hypoxemia a
      neuropathological investigation should give additional information to elucidate
      the cause of death and its pathophysiological mechanisms. Primary ischemic brain
      damage is associated with morphological and biochemical alterations. While acute
      ischemic neuronal injury reveals axon sparing and selective neuronal lesions due
      to the release of large quantities of glutamate, late neuronal death is
      associated with antiapoptotic growth factors, and decreased expression of
      microtubule-associated proteins and tubulin. On the morphological level ischemia
      can be detected by necrosis of neurons, proliferation of microglia, and
      astrocytes in vulnerable regions of the brain. In cases of permanent ischemia the
      so-called pale nervous cell injury is observed, in cases of partial perfusion the
      so-called dark nerve cell injury and apoptosis are detectable. In spite of the
      considerable advantages of recent research, presently there is no reliable
      qualitative marker to ascertain death due to acute hypoxic or ischemic events.

PMID- 16882235
TI  - Suicide with associated acts of arson: two cases from Colorado.
AB  - We report on two cases of suicide in which the victims started fires before their
      deaths. In one case the victim died of a single self-inflicted gunshot wound to
      the head after setting several fires in his residence. In the second case the
      victim hung himself after setting several fires in his residence and an adjoining
      building. In both cases, the victim's position was not near the origin of the
      fires suggesting that the arson was not a failsafe device to the primary
      mechanism of suicide. Neither victim showed a significant percentage of
      carboxyhemoglobin, or thermal damage from the fires. Both cases are remarkable in
      that, had the fire caused more damage to the remains and dwellings, a finding of
      suicide may not have been reached. We discuss similar aspects between the two
      reported cases and discuss differences observed with similar events such as
      complex suicide, suicide by self-immolation, and concealed homicide by burning.
      Similar cases should be reported to broaden our understanding of these complex
      events.

PMID- 16882234
TI  - Usefulness of dura mater in providing DNA samples for identifying cadavers.
AB  - We examined the usefulness of the dura mater in identifying human remains. Dura
      mater was collected from 50 cadavers, including drowned, charred, and mummified
      remains. The STR genotype using the AmpFlSTR Identifiler Kit could be typed at 15
      STR and amelogenin loci in 30 samples of 33 cases. Furthermore, the ABO genotype
      and amelogenin using gel-based methods could be typed in 44 samples of 50 cases.
      In cases with successful typing of STR, ABO-DNA, and amelogenin, the longest time
      after death was from 12 to 26 days in a drowned body. The minimum quantity of
      dura mater required for DNA extraction was about 2.5 mg, dried and fixed by
      ethanol, in a cadaver 15 h after death. The state of the DNA from the dura mater
      from the calvaria may be better than that from the basis cranii interna. We found
      that DNA from dura mater is one of the most useful samples for forensic
      identification.

PMID- 16882236
TI  - The association of alcohol-induced blackouts and grayouts to blood alcohol
      concentrations.
AB  - The primary aim of this study was to investigate the association between measured
      blood alcohol concentration (BAC) and the presence and degree of amnesia (no
      amnesia, grayout, or blackout) in actively drinking subjects. A secondary aim was
      to determine potential factors other than BAC that contribute to the alcohol
      induced memory loss. An interview questionnaire was administered to subjects
      regarding a recent alcohol associated arrest with a documented BAC greater than
      0.08 g/dL for either public intoxication, driving under the influence, or under
      age drinking was administered. Demographic variables collected included drinking
      history, family history of alcoholism, presence of previous alcohol-related
      memory loss during a drinking episode, and drinking behavior during the episode.
      Memory of the drinking episode was evaluated to determine if either an alcohol
      induced grayout (partial anterograde amnesia) or blackout (complete anterograde
      amnesia) occurred. Differences in (1) mean total number of drinks ingested before
      arrest, (2) gulping of drinks, and (3) BAC at arrest were found for those having
      blackouts compared with no amnesia; while differences in drinking more than
      planned were found between the no amnesia and grayout groups. A strong linear
      relationship between BAC and predicted probability of memory loss, particularly
      for blackouts was obvious. This finding clinically concludes that subjects with
      BAC of 310 g/dL or greater have a 0.50 or greater probability of having an
      alcoholic blackout.

PMID- 16882237
TI  - The motivation behind serial sexual homicide: is it sex, power, and control, or
      anger?
AB  - Controversy exists in the literature and society regarding what motivates serial
      sexual killers to commit their crimes. Hypotheses range from the seeking of
      sexual gratification to the achievement of power and control to the expression of
      anger. The authors provide theoretical, empirical, evolutionary, and
      physiological support for the argument that serial sexual murderers above all
      commit their crimes in pursuit of sadistic pleasure. The seeking of power and
      control over victims is believed to serve the two secondary purposes of
      heightening sexual arousal and ensuring victim presence for the crime. Anger is
      not considered a key component of these offenders' motivation due to its
      inhibitory physiological effect on sexual functioning. On the contrary, criminal
      investigations into serial sexual killings consistently reveal erotically charged
      crimes, with sexual motivation expressed either overtly or symbolically. Although
      anger may be correlated with serial sexual homicide offenders, as it is with
      criminal offenders in general, it is not causative. The authors further believe
      serial sexual murderers should be considered sex offenders. A significant
      proportion of them appear to have paraphilic disorders within the spectrum of
      sexual sadism. "sexual sadism, homicidal type" is proposed as a diagnostic
      subtype of sexual sadism applicable to many of these offenders, and a suggested
      modification of DSM criteria is presented.

PMID- 16882238
TI  - Gelatine lifting, a novel technique for the examination of indented writing.
AB  - The limitations of the examination of indented writing impressions using
      electrostatic detection are often paper related. Paper types such as glossy
      paper, paper of high basis weight, and lithography or gravure-printed papers
      often give rise to problems resulting in a decrease in sensitivity or a lack of
      detection altogether. In this paper, a novel technique for the examination of
      indented writing is presented, which is in a sense complimentary to the technique
      of electrostatic detection as it is especially suitable for glossy-coated and
      printed paper types and can in some instances also deal with paper types of
      higher basis weight. Indented writing grooves will normally contain more
      particles than the surrounding nonindented areas due to damage of the surface
      layer resulting in a build-up of filler powder. The method presented uses black
      gelatine lifter slabs to lift the paper dust image off the surface of the paper.
      This image can quite easily be photographed using near-to-coaxial lighting. The
      gelatine lifting method outperforms oblique lighting for the detection of
      indented writing and is almost as sensitive as electrostatic detection if
      compared on the types of paper where both perform well. The main advantage of
      this new technique is, however, that it is especially suitable for those types of
      paper where electrostatic detection fails and is therefore a welcome addition to
      the range of methods available to a forensic document examiner for the
      examination of indented writing.

PMID- 16882239
TI  - Differentiating writing inks using direct analysis in real time mass
      spectrometry.
AB  - Writing ink analysis is used in establishing document authenticity and the
      sources and relative ages of written entries. Most analytical methods require
      removing samples or visibly altering the document. Nondestructive, in situ
      analysis of writing inks on paper without visible alteration is possible using
      mass spectrometry with a new ion source called Direct Analysis in Real Time.
      Forty-three different black and blue ballpoint, black fluid, and black gel inks
      were examined. Both dyes and persistent but thermally labile components of the
      inks contribute to the mass spectra, principally as protonated molecules
      [M+H](+). Numerous ink components were identified from the spectra. The spectra
      were placed in a searchable library, which was then challenged with two spectra
      from each of the 43 inks. The best match for each of the challenge spectra was
      correct for all but one ink, which matched with a very similar ink by the same
      manufacturer.

PMID- 16882240
TI  - Classification of black powder toners on the basis of integrated analytical
      information provided by Fourier transform infrared spectrometry and X-ray
      fluorescence spectrometry.
AB  - Differentiating between black powder toners used in laser printers and copiers
      can be challenging for forensic examiners. One hundred and sixty-two samples from
      82 different types of cartridges produced by 21 manufacturers that are currently
      available on the Polish market were studied using Fourier transform infrared
      spectrometry (FT-IR) and energy-dispersive X-ray fluorescence spectrometry (XRF).
      The spectra obtained by these two methods were classified into 14 groups and 28
      groups using FT-IR and XRF, respectively. These classifications served as a basis
      for the development of an analytical scheme for differentiating black powder
      toners. This scheme can be used with any two methods that supply different
      information about an examined sample. The research will show that if two samples
      are similar in polymer composition (e.g., FT-IR spectra), additional quantitative
      elemental composition from XRF analyses may provide more discrimination. It was
      possible to differentiate 82.5% pairs of examined samples using only FT-IR, 90.8%
      pairs of examined samples using only XRF, and 95.8% pairs of examined samples
      using these two methods. Obtained spectra and all the available information could
      be used to create/build a database. The results obtained confirm the multiplicity
      and compatibility of toners. Additionally, it was stated that not all the samples
      were original (OEM).

PMID- 16882241
TI  - A simple microthermal desorption device.
AB  - A new method for thermal desorption of small samples is presented. The method
      uses a solid phase microextraction (SPME) holder with the fiber removed. The
      sample-for example, an ink sample on paper-is simply placed inside the needle of
      the holder, where normally an SPME fiber is positioned. The thermal desorption is
      then performed on any kind of gas chromatograph in a manner similar to that for
      SPME analysis. The needle of the SPME holder penetrates the injector septum; the
      temperature of the thermal desorption is simply the temperature of the injector.
      No solvents or liquid nitrogen cooling are used. The paper sample is kept inside
      the holder needle during the analysis. After the analysis is completed, the
      sample is removed from the needle by pushing forward the steel wire inside the
      needle in the way normally used to perform sampling with the SPME fiber. The
      desorbed compounds were analyzed by gas chromatography with a flame ionization
      detector or by gas chromatography-mass spectrometry. The optimum temperature for
      desorption of ink samples on paper was 200 degrees C. The influence of the paper
      matrix is negligible at that temperature. Laboratories lacking the commercial
      device for thermal desorption can use this cheap device for the analysis of, for
      example, writing ink, printing ink, and inkjet ink samples on paper. Other types
      of samples can be investigated but the size of samples suitable for analysis is
      limited.

PMID- 16882242
TI  - Examination of a "velasco" signature on an oil painting.
AB  - In September 2003, an investor bought an oil painting at auction in Denmark. The
      painting was signed "Jose Maria Velasco." The investor attempted to sell the
      painting in the United States, but found that he needed confirmation that this
      was an authentic Velasco painting. The provenance of the painting was
      questionable because it came to Europe from Cuba without appropriate
      documentation including the date of its entry into the European market. If the
      signature was determined to be authentic, the painting would have an approximate
      value of 1 million dollars. Initial research on the life and works of the artist
      and a literature review resulted in the preparation of an "Art Worksheet." Known
      signature specimens were obtained from reputable sources. A comparison of the
      known signatures with the questioned signature concluded the questioned signature
      was very probably not executed by Jose Maria Velasco.

PMID- 16882243
TI  - Commentary on: Divne A-M, Nilsson M, Calloway C, Reynolds R, Erlich H, Allen M.
      Forensic casework analysis using the HVI/HVII mtDNA linear array assay. J
      Forensic Sci 2005;50:548-54.

PMID- 16882245
TI  - Comparison of fentanyl extraction from two different transdermal patches.

PMID- 16882246
TI  - Fire setting in a patient with hyperglycaemic delirium.

PMID- 16882247
TI  - Allele frequencies and haplotypes of the 12 Y-STR loci using the PowerPlex Y
      system in Japanese population.

PMID- 16882248
TI  - Allele frequencies for three STR loci in Chinese Han populations.

PMID- 16882249
TI  - Allelic variation at ACTBP2 microsatellite for two Indian tribal groups.

PMID- 16882250
TI  - Allele frequencies for two STR loci D4S3251 and D8S2321 in Chinese population.

PMID- 16882251
TI  - Distribution of GATA86C08, GATA158G03, D11S2001 alleles in Chinese population
      sample.

PMID- 16882252
TI  - Allele frequencies for three STR loci D3S4551, D11S4465, and D18S973 in Chinese
      population.

PMID- 16882260
TI  - Auto-transplantation of the uterus in the domestic pig (Sus scrofa): Surgical
      technique and early reperfusion events.
AB  - AIM: To develop a method for auto-transplantation of the uterus in the pig and to
      evaluate the early reperfusion events after short-term cold ischemia. METHODS:
      The bicornate uterus, with the cervix but without ovaries, was dissected and
      isolated with its bilateral feeding and draining vessels. The uterine arteries
      were cannulated in situ and the uterus was flushed with heparinized Ringer
      Acetate. It was stored at 4 degrees C for 1-2 h during continuous flushing. The
      uterus was then placed in its original pelvic position and the uterine arteries
      and veins were anastomosed end-to-end to their origin. During approximately 100
      min of reperfusion, blood samples and tissue biopsies were taken for monitoring
      of reperfusion events and detection of ischemia-reperfusion injuries. RESULTS:
      Out of 19 auto-transplanted pigs, seven were considered well flushed and were
      kept for cold ischemia. Of these seven, four showed satisfactory reperfusion
      judged by change in gross appearance and presence of appropriate venous blood
      flow. Analysis of blood-gas and metabolite parameters and histology indicated
      that at least two of these transplants were well reperfused, with no severe
      ischemia-reperfusion injuries. CONCLUSION: In this first report ever on auto
      transplantation of the pig uterus it is demonstrated that an acceptable
      reperfusion can be achieved. Furthermore, it is suggested that because of the
      large total size of the pig uterus with long uterine horns and the small size of
      the vessels available for re-anastomosis, the pig is a fairly difficult model for
      further studies on transplantation of the uterus.

PMID- 16882261
TI  - Rapid detection of trisomy 21 by gene dosage analysis using quantitative real
      time polymerase chain reaction.
AB  - AIM: Rapid detection of fetal aneuploidy helps inform a mother's choice about the
      course of her pregnancy. Obtaining results by fluorescent in situ hybridization
      (FISH) requires more than 24 h, and thus a more rapid method is needed. METHODS:
      Conventional G-banding and FISH for chromosome 21 were performed for cultured
      amniocytes. Genomic DNA was extracted from uncultured amniocytes obtained from 23
      patients. TaqMan polymerase chain reaction (PCR) primers were designed to amplify
      the potassium voltage gated channel gene on chromosome 21q22.12 and the ribosomal
      phosphoprotein gene on 18q21.1. Quantitative real-time PCR was performed for
      these two gene fragments and the differences of the threshold cycle (Ct) of the
      two genes (Ct 18-Ct 21) were calculated for each sample. RESULTS: G-banding
      revealed that 19 patients had a normal karyotype and four had trisomy 21. FISH
      resulted in one case of a false positive. The Delta Ct values (Ct 18-Ct 21) of
      trisomy 21 patients were significantly higher than the values of individuals with
      normal karyotypes (P < 0.001) and there was no overlapping. CONCLUSIONS: Fetal
      trisomy 21 is rapidly detectable by gene dosage analysis from amniocytes using
      quantitative real-time PCR.

PMID- 16882262
TI  - Reduction of aquaporin-8 on fetal membranes under oligohydramnios in mice lacking
      prostaglandin F2 alpha receptor.
AB  - AIM: To investigate the association between aquaporin-8 (AQP-8: a water channel
      protein) expression in fetal membranes and oligohydramnios during near-term and
      postdate pregnancy, we set up an oligohydramnios model using prostaglandin F2
      alpha receptor (FP)-deficient mice. METHODS: Pregnant FP-deficient mice from 14
      to 21 gestational days (GD) were killed to measure the amniotic fluid volume
      (AFV), and fetal membranes were collected for the analysis of aquaporin-8
      expression. RESULTS: The AFV was highest at 14 GD, and was significantly
      decreased to 28% and 0% at 20 GD and 21 GD, respectively, compared with the
      volume at 14 GD. Immunohistochemistry and immunoblot analysis showed that
      aquaporin-8 was expressed in the basal component of fetal membranes, and that the
      protein level was significantly decreased to 60% at 20 GD compared with that at
      14 GD. CONCLUSIONS: We demonstrated that AQP-8 expression in the fetal membrane
      was decreased at post term in FP-deficient mice. Our findings suggest that
      aquaporin-8 in fetal membranes may be involved in the regulation of AFV,
      especially when oligohydramnios occurs.

PMID- 16882263
TI  - Significance of CD44v6 expression in gynecologic malignancies.
AB  - AIM: Variants of CD44 have been proposed to be important in cancer invasion and
      metastasis. The purpose of this study was to evaluate the diagnostic and
      prognostic value of CD44v6 expression in gynecologic malignancies. METHODS:
      Immunohistochemistry was used to determine the expression of CD44v6 in samples
      from a series of 65 cases of early cervical cancer, 76 cases of endometrial
      samples and 57 cases of serous epithelial ovarian tumors. We analyzed the
      expression of CD44v6 and correlated the findings with clinicopathological
      factors. RESULTS: In the cervical series, CD44v6 was detected in 60 cases of
      cervical cancer (92.3%). The immunoreactivity was decreased when stromal invasion
      reached a depth of more than 5 mm (P < 0.05). However, it was not correlated with
      other clinicopathological factors. In the endometrial series, CD44v6 was detected
      in one endometrial hyperplasia (6.7%) and in 24 endometrial cancers (100%), while
      it was not detected in the proliferative endometrium (P < 0.05). Immunoreactivity
      was decreased in grade 2 and 3 endometrial cancers compared with grade 1 (P <
      0.05). In the ovarian series, CD44v6 was not detected in the benign tumors, but
      it was detected in four borderline malignancies (27%) and 12 carcinomas (40%).
      Immunoreactivity was not correlated with clinicopathological factors of ovarian
      cancer. CONCLUSION: CD44v6 may be involved in stromal invasion of early squamous
      cervical carcinomas and in the cellular differentiation of endometrial cancer. In
      addition, it may be useful for early diagnosis of endometrial cancer.

PMID- 16882264
TI  - Ovarian carcinomas with neuroendocrine differentiation: Review of five cases
      referring to immunohistochemical characterization.
AB  - AIM: To review five ovarian carcinomas with varying degrees of neuroendocrine
      differentiation (ND) using an immunohistochemical study focused on the
      relationship with morphological features. METHODS: ND was immunohistochemically
      analyzed using 21 antibodies by an indirect immunoperoxidase method, and ploidy
      pattern was analyzed using paraffin sections. RESULTS: The tumors were divided
      according to tumor cell size into 'small-sized' for case 1, 'intermediate-sized'
      for cases 2 and 3, and 'large-sized' for cases 4 and 5. Expressions of
      neuroendocrine markers and argyrophil reaction tended to be strengthened as tumor
      cell size increased. Cases 1, 2 and 3 showed diploid pattern and cases 4 and 5
      showed aneuploid pattern. CONCLUSION: ND of ovarian carcinomas is closely related
      to morphological features represented by the cell size. Therefore, ovarian
      carcinomas with ND should be defined because the disease entity is not
      successfully integrated irrespective of the highly malignant potential.

PMID- 16882265
TI  - Prospective study of non-closure or closure of the peritoneum at cesarean
      delivery in 124 women: Impact of prior peritoneal closure at primary cesarean on
      the interval time between first cesarean section and the next pregnancy and
      significant adhesion at second cesarean.
AB  - AIM: The aim of this study was to evaluate the effect of non-closure of the
      peritoneum at cesarean delivery on postoperative complications and the interval
      time to the next pregnancy, and to investigate the incidence of adhesion
      following cesarean and the association between adhesion formation and peritoneal
      closure. METHODS: One hundred and twenty four women scheduled for cesarean
      section were randomized to either closure of both the visceral and parietal
      peritoneum (C-group, n = 70) or non-closure (NC-group, n = 54). At repeated
      cesarean, the levels and extent of adhesion, operating time, and any
      complications were examined. RESULTS: There was no difference in the incidence of
      postoperative complications at the first cesarean section. The operating time of
      the C-group was significantly longer than that of the NC-group. The frequency of
      analgesic use was significantly higher in the C-group. The time interval from
      cesarean section to the next pregnancy in the NC-group was significantly shorter
      than that in the C-group. There are no significant differences between the rates
      of complications in the C-group and the NC-group at repeated cesarean. The
      incidence of adhesion in the C-group was significantly higher than that in the NC
      group (P < 0.05). The mean total operating time and the mean interval time for
      skin incision to delivery in the C-group were significantly longer than those in
      the NC-group (P < 0.05 and P < 0.001, respectively) at repeated cesarean section.
      CONCLUSIONS: Non-closure of the peritoneum at cesarean delivery appears to have
      no adverse effect on postoperative recovery, it also decreases the number of
      analgesic doses and shortens the operating time and may be more desirable in
      achieving a next pregnancy. The present study demonstrated that surgical
      peritoneal closure resulted in more advanced adhesion formation. The practice of
      non-closure of the peritoneum should be performed at cesarean.

PMID- 16882266
TI  - Mid-second trimester measurement of fetal nasal bone length in the Japanese
      population.
AB  - AIM: We carried out a preliminary study to compare the nasal bone length (NBL)
      and biparietal diameter/NBL (BPD/NBL) ratio between the Japanese and white
      populations. METHODS: Three hundred and fifty nine (359) singleton fetuses of
      healthy Japanese couples were examined from June 2004 to October 2005. NBL was
      measured by the strict midsagittal section. The reference range of NBL was
      established from cross-sectional data between 15 and 25 weeks' gestation.
      RESULTS: The success rate of obtaining reliable NBL was 93% (333/356). There were
      330 fetuses (93%) available for constructing a reference range from the
      population. The median NBL increased from 3.2 mm at 15 weeks' to 7.6 mm at 25
      weeks' gestation. The median of BPD/NBL ratio was 9.01. CONCLUSIONS: We
      demonstrated that NBL was significantly shorter and BPD/NBL was significantly
      greater in the Japanese population than those in the white and black populations.

PMID- 16882267
TI  - Metabolic disorders in patients with recent gestational diabetes mellitus.
AB  - AIM: To determine metabolic disorders in patients with recent gestational
      diabetes mellitus (GDM) compared with controls. METHODS: Thirty-six patients with
      recent GDM and treated with a diabetic diet only, and 33 controls with normal
      pregnancies, were included in the study. An oral glucose tolerance test, with
      corresponding insulin and hormone levels, was performed; the homeostatic model
      assessment scores were calculated to estimate insulin resistance; prevalence of
      polycystic ovarian morphology on ultrasound scan was assessed; and results were
      recorded 10-15 months after delivery. RESULTS: Waist : hip ratio and fasting
      cholesterol and triglyceride levels were significantly higher in women with
      recent GDM; high-density lipoprotein cholesterol did not differ between groups.
      Fasting, 1-h and 2-h plasma glucose levels were significantly higher in the GDM
      group; no statistically significant difference was found between groups regarding
      fasting insulin levels, 1-h and 2-h insulin response, and homeostatic model
      assessment scores. Serum hormone levels did not differ between groups. The
      prevalence of polycystic ovarian morphology was greater in women with GDM. There
      was no difference in any metabolic parameter between women in the GDM group with
      polycystic ovaries and those with normal ovaries. CONCLUSIONS: We found a higher
      prevalence of polycystic ovarian morphology in women with GDM than in controls.
      Among women with recent GDM, higher waist : hip ratios and fasting plasma glucose
      and triglyceride levels may indicate metabolic syndrome. In women with recent GDM
      managed by diet only, insulin resistance may not be detected in the short term.

PMID- 16882268
TI  - Fertility-preserving treatment for patients with malignant germ cell tumors of
      the ovary.
AB  - AIM: The aim of this study was to investigate whether fertility preservation
      influences the clinical outcome in patients with malignant germ cell tumors of
      the ovary (MGCTO). METHODS: A case study analysis was performed on patients with
      MGCTO treated at Kurume University Hospital between 1986 and 2004. Thirty-five
      patients were included in the study, 14 with immature teratoma, 11 with
      dysgerminoma, eight with endodermal sinus tumor, and two with mixed germ cell
      tumor. Twenty-three patients had International Federation of Gynecology and
      Obstetrics stage I (Ia, 11; Ib, 2; Ic, 10), one had stage II, seven had stage
      III, and four had stage IV disease. RESULTS: Five patients with stage III or IV
      disease received radical surgery. Thirty patients underwent conservative surgery.
      As the adjuvant treatment, 30 patients received chemotherapy, while five patients
      did not receive any chemotherapy. The overall survival rate was 97.1%. One
      patient died of the disease. She was 13 years old with a stage IV endodermal
      sinus tumor. Twelve have attempted conception, and eight have achieved at least
      one pregnancy (66.7%). CONCLUSIONS: Irrespective of the stage of the disease,
      conservative surgery and adjuvant chemotherapy for MGCTO can achieve a favorable
      outcome in terms of survival and fertility.

PMID- 16882269
TI  - CA-125 levels in ruptured and unruptured tubal ectopic pregnancies.
AB  - AIM: This prospective, single-blind and controlled clinical study aimed to
      research if CA-125 levels could be a useful test in the differential diagnosis of
      intact and ruptured tubal ectopic pregnancy. METHODS: Sixty-five women with tubal
      ectopic pregnancy of 5-10 weeks' duration (27 women with ruptured tubal ectopic
      pregnancy [REP] and 38 women with unruptured tubal ectopic pregnancy [UREP]) and
      65 women with normal intrauterine pregnancy (NIUP) of the same gestational age
      were studied prospectively. Serum CA-125 levels were measured in all women and
      these levels were compared among the REP, UREP, and NIUP groups. RESULTS: The
      mean CA-125 levels didn't show any significant difference between the REP and
      NIUP groups (P > 0.05). The mean CA-125 levels of these two groups were higher
      than that in the UREP group (P < 0.01, P < 0.001, respectively). The dispersion
      ratios of the CA-125 levels had a statistically significant difference between
      the REP and UREP groups (chi(2): 42.44, P < 0.0001). CA-125 levels weren't
      correlated with gestational weeks in the REP and UREP groups (r: 0.005, P > 0.05;
      r: 0.008, P > 0.05, respectively). CONCLUSION: In intact tubal ectopic
      pregnancies, expectant or managed with medical treatment, the increase of CA-125
      levels in the serial measurements could be a supplementary test for an early
      diagnosis of tubal rupture.

PMID- 16882270
TI  - Effect of thread pitch on pull-out strength of laparoscopic myoma screws.
AB  - AIM: The purpose of this study was to evaluate the effect of thread-pitch on pull
      out strength and bending strength of buttress-thread screws designed for
      laparoscopic myoma extraction. METHODS: The ultimate failure load of four 5-mm
      diameter buttress-thread screws with 3-, 4-, 5-, and 6-mm thread pitch, 40 mm in
      thread-length were examined on fresh myoma specimens. The myoma tissue at each
      traction site was evaluated histologically to determine its density. The critical
      minimal pull-out strength based on moderate-density myoma group was estimated.
      The bending strength was also determined for each screw. RESULTS: A wide range of
      ultimate failure loads with a mean +/- SE of 129.3 +/- 5.5 N (range, 30.4-255.7
      N) for all screws and tissue densities was recorded. In moderate-density myomas,
      the mean ultimate failure loads decreased linearly with increasing thread-pitch
      from 3 mm (148.0 +/- 9.5 N) to 6 mm (119.8 +/- 9.4 N) (test for trend: P < 0.05).
      Based on the criterion of a minimum pull-out strength of at least 50 N in not
      less than 95% of tractions in medium-density myomas, the 3-mm and 5-mm pitch
      screws were found to have acceptable properties. The 5-mm pitch screw had less
      thread-turn than the 3-mm pitch for the same thread-length and would need less
      application time. The bending strength also decreased with increasing thread
      pitch from 3 to 5 mm, then became stable at around 15 N. CONCLUSIONS: The pull
      out strength of soft tissue buttress-thread screws decreased linearly with
      increasing thread-pitch. Thread-pitch should be considered when designing
      laparoscopic myoma-screws.

PMID- 16882271
TI  - Small bowel perforation from a thermal burn caused by contact with the end of a
      laparoscope during ovarian cystectomy.
AB  - Although laparoscopic surgery now replaces many gynecologic laparotomy
      procedures, serious complications unique to laparoscopy may occur, including
      vascular or bowel injury. In most cases of bowel injury during laparoscopy, the
      laparoscopic instruments that cause injury are the trocar, Veress needle,
      grasping forceps or scissors, electrocoagulator, or laser. We report a rare case
      of small bowel perforation after a thermal burn caused by contact with the end of
      the scope during laparoscopic ovarian cystectomy. Burns and perforations of the
      small bowel during laparoscopy are rare complications preventable by familiarity
      with the physical properties of the laparoscopic instruments.

PMID- 16882272
TI  - Evolution and management of a hepatocellular carcinoma during pregnancy.
AB  - Coexistence of a hepatocellular carcinoma with pregnancy is extremely rare. The
      authors present the case of an African woman positive for hepatitis B surface
      antigen and referred to our hospital for suspected cervical incompetence in which
      a surgically unapproachable hepatocellular carcinoma was diagnosed. The patient
      refused termination of pregnancy or liver transplantation because of religious
      beliefs. In this case, the authors had the opportunity to follow the growth of
      the mass throughout the pregnancy and puerperium.

PMID- 16882274
TI  - Interpreting trends in cancer patient survival.
AB  - Data on cancer patient survival are an invaluable tool in the evaluation of
      therapeutic progress against cancer as well as other lethal diseases. As with all
      quantitative information routinely used in evidence-based clinical management-
      including diagnostic tests, prognostic markers and comparisons of therapeutic
      interventions--data on patient survival require evaluation based on an
      understanding of the underlying statistical methodology, methods of data
      collection and classification, and, most notably, clinical and biologic insight.
      This article contains an introduction to the methods used for estimating cancer
      patient survival, including cause-specific survival, relative survival and period
      analysis. The methods, and their interpretation, are illustrated through
      presentation of trends in incidence, mortality and patient survival for a range
      of different cancers. Our aim was to lay out the strengths and limitations of
      survival analysis as a tool in the evaluation of progress in the diagnosis and
      treatment of cancer.

PMID- 16882275
TI  - Clinical and angiographic follow-up after coronary drug-eluting and bare metal
      stent implantation. Do drug-eluting stents hold the promise?
AB  - OBJECTIVES: To investigate the influence of drug-eluting stent (DES) implantation
      on clinical and angiographic restenosis. DESIGN: Registry study of data from the
      Swedish Coronary Angiography and Angioplasty Registry with a coronary
      angiographic substudy. SETTING: Multi-centre study. SUBJECTS: During October 2002
      to May 2004 a total of 23 590 percutaneous coronary intervention (PCI) procedures
      were performed at 25 hospitals. After selection, to achieve comparable groups, a
      total of 5068 patients of whom 4111 had a bare metal stent (BMS) implanted and
      957 had a DES implanted, remained. End-point in the registry follow-up was >50%
      diameter restenosis at clinically driven reangiography within 12 months after
      index PCI. The primary end-point in the angiographic substudy was late loss in
      patients' DES at 6-month angiographic follow-up. RESULTS: The rate of clinically
      driven restenosis, within 12 months, in patients receiving DES was less (3.9%)
      compared with those who received BMS (7.0%). In multivariate analysis the risk of
      clinical restenosis was one-third for DES compared with BMS (HR 0.36, 95% CI 0.25
      0.52). In the angiographic substudy late loss was 0.07+/-0.53 mm (range -0.88 to
      1.62). The amount of late loss was related to the presence of diabetes mellitus
      or not (0.19+/-0.45 mm vs. -0.12+/-0.58 mm), and lack of postdilatation of the
      stent or not (0.23+/-0.51 mm vs. -0.09+/-0.50 mm). CONCLUSIONS: The use of DES in
      the Swedish 'real world' is effective in reducing the clinically driven
      restenosis rate, when compared with patients with BMS treatment. In the
      angiographic follow-up the average late loss was as low as observed in recent
      randomized multi-centre trials.

PMID- 16882277
TI  - Population-attributable risk of coronary heart disease risk factors during long
      term follow-up: the Malmo Preventive Project.
AB  - AIMS: To calculate the population-attributable risk (PAR) of coronary events (CE)
      from 10 risk factors, during long-term follow-up. METHODS: We used both case
      cohort and case-control analyses for calculation of PAR in relation to 10
      baseline risk factors. First CE (fatal or nonfatal, n=3072) in 22,444 males and
      10,902 females was recorded during a mean follow-up of 20 years by use of
      national registers. RESULTS: Using a Cox regression analysis in a case-cohort
      design, smoking (prevalence in men 49%, women 37%) was the strongest risk factor,
      RR 2.29 (95% CI 2.09-2.52; PAR 39%), followed by hypercholesterolaemia, RR 1.70
      (95% CI 1.56-1.86; PAR 18%), and diabetes, RR 1.67 (95% CI 1.41-1.99; PAR 3%).
      For women the strongest risk factors were smoking, RR 3.16 (95% CI 2.50-3.98; PAR
      44%), diabetes, RR 2.59 (95% CI 1.78-3.76; PAR 6%), and hypertension, RR 2.47
      (95% CI 1.94-3.14; PAR 23%). In men, smoking was the strongest predictor both
      after 10 years [RR 2.69 (95% CI 2.23-3.24)] and 20 years [RR 2.45 (95% CI 2.15
      2.79)], followed by hypercholesterolaemia (RR 2.16-1.63), hypertension (RR 2.04
      1.51), and diabetes (RR 1.85 -1.47). The case-control design gave very similar
      results. Total PAR varied from 74% (fully adjusted Cox regression, case-control,
      in men) to 116% in women (case-cohort). CONCLUSION: Smoking is the most important
      long-term risk factor for CE in both genders, based on data from a population
      with a high proportion of smokers. Ten measured variables explained almost all
      variation in risk and could be used as a basis for intervention programmes.

PMID- 16882276
TI  - Glycaemic and nonglycaemic effects of pioglitazone in triple oral therapy of
      patients with type 2 diabetes.
AB  - OBJECTIVES: To examine pioglitazone as add-on to metformin and insulin
      secretagogues in patients with type 2 diabetes and inadequate glycaemic control
      and its effect on glycaemic control, surrogate measures of insulin sensitivity
      (adiponectin) and beta-cell function (proinsulin/insulin) and fluid retention.
      DESIGN AND SETTING: Prospective open-label study of 54 patients with type 2
      diabetes and HbA1c>or=6.5% admitted to outpatient unit at Malmo University
      Hospital. The patients received 30-45 mg pioglitazone daily during 26 weeks in
      addition to their existing antidiabetic medication. After 26 weeks, one-third of
      patients were followed for 3 months without pioglitazone. RESULTS: HbA1c
      decreased (7.8+/-0.9-6.3+/-0.9%, P<0.001) with 61% of patients achieving
      levels<6.5%. However, in the group followed for another 3 months HbA1c increased
      (6.1+/-0.73-7.1+/-0.9, n=18, P<0.001) after pioglitazone withdrawal. Adiponectin
      increased (6.1+/-2.8-13.2+/-5.8 microg mL-1, P<0.001) and the proinsulin to
      insulin ratio decreased (0.89+/-0.66-0.66+/-0.53, P<0.001). Nt-proBNP increased
      from 487.3+/-252.2 to 657.8+/-392.1 pmol L-1 (P<0.001). CONCLUSIONS: Pioglitazone
      is effective in achieving glycaemic targets and reducing risk factors involved in
      atherosclerosis and improving beta-cell function when used as part of triple oral
      therapy in patients with type 2 diabetes and secondary drug failure. Nt-proBNP
      increase with concomitant decrease in haemoglobin suggests a subclinical sign of
      fluid retention.

PMID- 16882278
TI  - Noninvasive ratio indexes to evaluate fibrosis staging in chronic hepatitis C:
      role of platelet count/spleen diameter ratio index.
AB  - OBJECTIVES: Noninvasive evaluation of fibrosis is an on-going effort in the
      management of chronic hepatitis C. This study was planned to noninvasively
      evaluate fibrosis staging. DESIGN: We evaluated the biochemical, functional
      [aminopyrine breath test (ABT)] and ultrasonographic variables of 75 chronic
      hepatitis C patients. RESULTS: Clinical [body mass index (BMI)], biochemical
      [aspartate aminotransferase (AST), alanine aminotransferase (ALT) and platelets
      (PLT)] and ratio indexes, together with the ABT, showed a higher relationship
      with fibrosis: initial (score<or=2) versus evident (score>2) fibrosis: BMI (24+/
      2 vs. 26+/-2, P=0.0007), AST (56+/-36 vs. 88+/-65, P=0.0159), ALT (92+/-54 vs.
      139+/-108, P=0.0290), PLT (220+/-64 vs. 173+/-61, P=0.0007), PLT/spleen diameter
      ratio (PLT/SPD) (2133+/-786 vs. 1540+/-681, P=0.0003), AST/platelet count ratio
      index (APRI) (0.80+/-0.87 vs. 1.51+/-1.47, P=0.0010), ABT%d/h30 min (10.8+/-4.5
      vs. 7.6+/-3.8, P=0.0007), ABT%d/cum120 min (8.9+/-3.3 vs. 6.5+/-3.1, P=0.0007).
      Considering the differences between fibrosis score 2 and 3 patients, BMI, ABT and
      PLT/SPD ratio proved to be statistically significant. Multivariate stepwise
      analysis (with and without BMI) identified two models for distinguishing between
      initial and evident fibrosis: Model 1: -0.569+(BMIx0.107)+(APRIx0.169)
      (PLT/SPDx0.304), and Model 2: 2.376+( APRIx0.152)-(ABTd/h30x0.043)
      (PLT/SPDx0.249). These models showed concordance in identifying or ruling out
      evident fibrosis in 76% and 78.7% of the patients respectively. The PLT/SPD ratio
      also showed 78.7% concordance with the histological score. CONCLUSION: These
      results suggest that noninvasive evaluation of fibrosis in chronic hepatitis C
      may be considered an effective tool thanks to the use of an inexpensive,
      reproducible ratio index.

PMID- 16882279
TI  - Plasma cholesteryl ester transfer protein concentrations predict cardiovascular
      events in patients with coronary artery disease treated with pravastatin.
AB  - OBJECTIVE: The B1B1 variant of the cholesteryl ester transfer protein (CETP)
      TaqIB polymorphism and high plasma CETP concentrations are associated with
      favourable angiographic outcomes in pravastatin-treated patients suffering from
      coronary artery disease (CAD). The purpose of the present study was to test
      whether CETP TaqIB genotypes and/or plasma CETP concentrations at baseline also
      predict clinical end-points in patients with CAD. DESIGN: Prospective
      longitudinal observational study. SETTING: Primary care doctors (n=88) and
      hospitals (n=7) in Austria. SUBJECTS: A total of 1620 men and women with
      preexisting CAD were recruited and plasma lipids were determined at study entry.
      1389 hypercholesterolaemic patients were included and 1002 patients completed the
      follow-up. INTERVENTIONS: In all patients treatment with pravastatin was started
      and patients were followed up for 2 years. MAIN OUTCOME MEASURES: Cardiovascular
      events. RESULTS: One hundred patients suffered at least one cardiovascular event.
      We observed significantly more events in patients within the lowest compared with
      the highest quartile of plasma CETP concentrations (odds ratio 3.20, CI95 1.65
      6.23; P=0.001, adjusted for known risk factors of CAD). No significantly
      different numbers of cardiovascular events were found between CETP TaqIB
      genotypes. CONCLUSIONS: Plasma CETP concentrations, but not CETP TaqIB genotypes,
      predict cardiovascular events in patients with CAD treated with pravastatin.
      Despite higher LDL cholesterol concentrations, high plasma CETP concentrations at
      baseline are associated with fewer cardiovascular events compared with low plasma
      CETP concentrations in CAD patients treated with pravastatin.

PMID- 16882280
TI  - Spinal tuberculosis: overlooked?
AB  - OBJECTIVE: The aim of the present study was to ascertain the degree of occurrence
      of tuberculous infection in patients presenting with low back pain (LBP).
      METHODS: Forty consecutive patients seeking primary medical attention for the
      main symptom of LBP and presenting to the Rheumatology Outpatient Clinic of our
      institution from January 2004 to June 2005, were recruited in this cohort study.
      All patients were thoroughly interrogated (occupational, trauma, infection,
      diabetes mellitus and medication history), subjected to a rigorous clinical
      examination and a battery of investigations RESULTS: Twelve of the 40 patients
      (33%) proved to have spinal TB as the cause of backache. Eight of these patients
      were above the age of 65. Five of the 12 patients with spinal TB also had
      concomitant osteoarthritic changes of the spine and two patients had concomitant
      disc prolapse. Eleven of the 12 patients with spinal TB had a completely normal
      chest X-ray and in 10 of these patients the plain X-ray of the lumbosacral region
      failed to show any significant lesion. In all 12 patients, sputum analysis failed
      to reveal acid-fast bacilli. CONCLUSIONS: The findings of this study indicate
      that TB is a common cause of LBP that is liable to be overlooked in the
      differential diagnosis of LBP. Furthermore, evidence of concurrent active
      intrathoracic TB may be lacking and consequently a high level of suspicion is
      required. The need for prompt diagnosis and treatment of skeletal TB is of utmost
      importance to prevent serious bone and joint destruction and severe neurological
      sequelae. A reliable imaging modality for diagnosing spinal TB seems to be
      magnetic resonance imaging.

PMID- 16882281
TI  - Intravenous immunoglobulin-associated cranial pachymeningitis.
AB  - To date, intravenous immunoglobulin (IvIg) has more often been considered as a
      safe medication. However, with the wider use of IvIg, severe side effects have
      also been reported to occur in IvIg-treated patients, notably aseptic meningitis.
      Other neurological complications have more rarely been described in patients
      receiving IvIg therapy, e.g. stroke or acute encephalopathy. We recently observed
      a case which is of particular interest, as the patient with steroid-refractory
      polyarteritis nodosa developed cranial pachymeningitis related to IvIg therapy.
      To our knowledge, this is the first reported case of cranial pachymeningitis
      complicating IvIg therapy. Our findings emphasize the importance of recognizing
      IvIg-related neurological complications in IvIg-treated patients. As cranial
      pachymeningitis is a fibrosing process, both recognition and management at an
      early stage are required to prevent definite neurological impairment in patients.

PMID- 16882282
TI  - A prospective observational study of a cohort of outpatients with an acute
      medical event and reduced mobility: incidence of symptomatic thromboembolism and
      description of thromboprophylaxis practices.
AB  - OBJECTIVES: The study was performed to determine the incidence of symptomatic
      venous thromboembolism in outpatients with an acute medical event causing
      temporary reduced mobility. Risk factors for venous thromboembolism and
      thromboprophylaxis practices were also studied. DESIGN: This was a prospective,
      observational, multicentre, cohort study. SETTING: General practitioners randomly
      selected from a registry of 25,000 active representative doctors in France
      including eligible outpatients. SUBJECTS: Outpatients aged at least 40 years
      anticipated to have reduced mobility for at least 48 h due to an acute medical
      event were eligible. INTERVENTIONS: None required. MAIN OUTCOME MEASURES:
      Symptomatic deep-vein thrombosis and pulmonary embolism at 3 weeks were the main
      study end-points. RESULTS: Overall, 16,532 evaluable patients of mean age 71
      years were recruited between October 2002 and June 2003 by 2895 doctors. The main
      acute medical events leading to reduced mobility were infection, acute rheumatism
      and falls without fracture. The incidence rates (95% confidence interval) of
      symptomatic deep-vein thrombosis and pulmonary embolism were 1% (0.84-1.14) and
      0.20% (0.13-0.27) respectively. Venous insufficiency in legs, cancer, and a
      personal or family history of venous thromboembolism were independent risk
      factors for venous thromboembolism. Pharmacological thromboprophylaxis was
      initiated in 35.0% (n=5782) of the patients. The principal driver of prescription
      was a personal history of venous thromboembolism. CONCLUSIONS: The risk of
      symptomatic venous thromboembolism in outpatients with reduced mobility for
      medical reasons is close to that reported in medical and surgical inpatients.
      This risk and the potential need for thromboprophylaxis should be taken into
      account by primary care doctors.

PMID- 16882283
TI  - Normalization of serum calcium by cinacalcet in a patient with hypercalcaemia due
      to a de novo inactivating mutation of the calcium-sensing receptor.
AB  - Familial benign hypocalciuric hypercalcaemia (FHH) results from a heterozygous
      inactivating mutation of the calcium-sensing receptor (CaR) and is characterized
      by hypercalcaemia, hypocalciuria and inappropriately normal plasma levels of
      parathyroid hormone. In a minority of patients, a loss of function mutation of
      the CaR results in severe hypercalcaemia associated with complications for which
      no effective surgical or medical treatment is available. We investigated the
      effects of the calcimimetic agent cinacalcet, an allosteric modulator of the CaR,
      in a 26-year-old man presenting with hypercalcaemia due to a de novo inactivating
      mutation of the CaR. Complicating features were recurrent psychosis and
      progressive severe osteoporosis. A single dose of either 30 or 60 mg of
      cinacalcet resulted in a 63-88% decline in plasma parathyroid hormone levels
      within 2 h of administration of the agent, reverting to baseline levels after 12
      h. Normalization of serum calcium was more gradual but sustained for up to 12
      months of treatment with a maintenance twice-daily oral dose of 60+30 mg
      cinacalcet. In addition to its beneficial effects in primary and secondary
      hyperparathyroidism, cinacalcet may open new therapeutic avenues in the
      management of a subset of patients with severe hypercalcaemia due to inactivating
      mutations of the CaR.

PMID- 16882284
TI  - Lipoprotein (a) and risk of cardiovascular disease in patients with metabolic
      syndrome in a population of familial hypercholesterolaemia.

PMID- 16882286
TI  - Quinolones for brucellosis: treating old diseases with new drugs.
AB  - Although quinolones are theoretically interesting candidates for the treatment of
      brucellosis, the existing data concerning their efficacy are limited and
      conflicting. A number of small clinical studies with combination regimens that
      include quinolones have shown adequacy, but not superiority, although cost
      effectiveness, excluding certain disease complications, is an important issue.
      The emergence of quinolone resistance and its implications is another drawback.
      Experimental data have yielded contradictory results, although most studies do
      not indicate a bactericidal effect for quinolones. However, in-vitro studies
      contrast repeatedly with the clinical response, both in terms of clinical
      failure, despite in-vitro success, and vice versa.

PMID- 16882287
TI  - Carbapenem resistance in Acinetobacter baumannii: mechanisms and epidemiology.
AB  - The increasing trend of carbapenem resistance in Acinetobacter baumannii
      worldwide is a concern since it limits drastically the range of therapeutic
      alternatives. Metallo-beta-lactamases (VIM, IMP, SIM) have been reported
      worldwide, especially in Asia and western Europe, and confer resistance to all
      beta-lactams except aztreonam. The most widespread beta-lactamases with
      carbapenemase activity in A. baumannii are carbapenem-hydrolysing class D beta
      lactamases (CHDLs) that are mostly specific for this species. These enzymes
      belong to three unrelated groups of clavulanic acid-resistant beta-lactamases,
      represented by OXA-23, OXA-24 and OXA-58, that can be either plasmid- or
      chromosomally-encoded. A. baumannii also possesses an intrinsic carbapenem
      hydrolysing oxacillinase, the expression of which may vary, that may play a role
      in carbapenem resistance. In addition to beta-lactamases, carbapenem resistance
      in A. baumannii may also result from porin or penicillin-binding protein
      modifications. Several porins, including the 33-kDa CarO protein, that constitute
      a pore channel for influx of carbapenems, might be involved in carbapenem
      resistance.

PMID- 16882288
TI  - Epidemiology of multiple Acinetobacter outbreaks in The Netherlands during the
      period 1999-2001.
AB  - An increase in the number of outbreaks of Acinetobacter infection was notified in
      The Netherlands during 1999-2001. The present study compared the outbreaks at the
      species and strain levels, and analysed the epidemiology and control measures at
      the different locations. For each institute, three representative isolates from
      three patients were identified to the species and strain levels by genotyping
      methods. A questionnaire investigated the impact of the outbreak, the control
      measures that were taken, and the possible effects of the measures. Seven
      outbreaks were associated with Acinetobacter baumannii (three outbreaks with a
      strain designated strain A, two outbreaks with a strain designated strain B, and
      one outbreak each with strains designated C and D). An additional outbreak was
      caused by genomic species 13TU, which is related closely to A. baumannii. Strains
      B and D were identified as European clones III and II, respectively. Except for
      two hospitals with outbreaks caused by strain A, there was no known
      epidemiological link between the participating hospitals. In all hospitals the
      outbreak occurred on one or several intensive care units, and spread to other
      departments was noted in two hospitals. The number of patients affected ranged
      from six to 66 over a period of 2-22 months. In most outbreaks, patients were the
      likely reservoir from which spread occurred. In all hospitals, a large panel of
      measures was required to bring the outbreak to an end. Extensive environmental
      sampling yielded numerous positive samples in most but not all hospitals.

PMID- 16882289
TI  - Antimicrobial susceptibility of gram-positive bacteria isolated from European
      medical centres: results of the Daptomycin Surveillance Programme (2002-2004).
AB  - The antimicrobial susceptibility patterns of 9322 contemporary (2002-2004) gram
      positive bacterial isolates collected from 31 medical centres in 14 countries in
      Europe were evaluated by broth microdilution methods according to CLSI
      guidelines. The isolates collected comprised Staphylococcus aureus (4842
      isolates), coagulase-negative staphylococci (CoNS; 1942 isolates), Enterococcus
      faecalis (1147 isolates), Enterococcus faecium (391 isolates), beta-haemolytic
      streptococci (660 isolates) and viridans group streptococci (340 isolates). The
      organisms were tested against daptomycin and more than 20 comparator agents in
      Mueller-Hinton broth, supplemented with calcium to 50 mg/L when testing
      daptomycin. Overall, methicillin (oxacillin) resistance rates were 26.7% and
      77.0% for S. aureus (MRSA) and CoNS, respectively, and the vancomycin resistance
      rate among enterococci was 6.1%. MRSA rates varied from 0.6% in Sweden to 40.2
      43.0% in Belgium, Greece, Ireland, the UK and Israel, and VRE rates varied from
      0% in Switzerland to 21.2% in Ireland. More than 99.9% of isolates tested were
      considered susceptible to daptomycin according to breakpoints established by the
      United States Food and Drug Administration and the CLSI. Daptomycin was active
      against all gram-positive species, with the highest MIC being 2, 8, 0.5 and 2
      mg/L for staphylococci, enterococci, beta-haemolytic streptococci and viridans
      group streptococci, respectively. Daptomycin activity was not influenced
      adversely by resistance to other agents among staphylococci or enterococci. This
      novel lipopeptide (daptomycin) appears to be an excellent alternative therapeutic
      option for serious infections caused by multidrug-resistant gram-positive
      organisms isolated in Europe.

PMID- 16882290
TI  - Antimicrobial resistance of nasopharyngeal pneumococci from children from day
      care centres and orphanages in Russia: results of a unique prospective
      multicentre study.
AB  - This study assessed the antimicrobial resistance of nasopharyngeal pneumococci
      isolated from children aged < 5 years in day-care centres and orphanages
      throughout Russia during 2001-2002. Swabs were collected from 2484 children in 43
      day-care centres and eight orphanages in 11 cities of European Russia, and from
      1669 children in 37 day-care centres and three orphanages in eight cities of
      Asian Russia, with a total of 1144 and 912 Streptococcus pneumoniae isolates
      being recovered in European and Asian Russia, respectively. All macrolide-non
      susceptible (MICs 0.5-128 mg/L) and fluoroquinolone-non-susceptible
      (ciprofloxacin MICs > or = 4 mg/L) isolates were tested for resistance mechanisms
      and clonal relatedness. Non-susceptibility rates, by CLSI criteria, were 19.3%,
      0.9% and 0.4% for penicillin G, cefotaxime and amoxycillin-clavulanate,
      respectively. Resistance to macrolides and lincosamides was also relatively low,
      i.e., < 7% for clindamycin and 14- and 15-membered macrolides. The highest rates
      of non-susceptibility were for tetracycline and co-trimoxazole (52.0% and 64.5%,
      respectively). No clones resistant to ciprofloxacin (MICs > or = 8 mg/L) were
      found, but 1.7% of isolates were non-susceptible (MIC 4 mg/L). No resistance was
      found to levofloxacin, gemifloxacin, telithromycin or vancomycin. Pulsed-field
      gel electrophoresis analysis showed no relationship between ciprofloxacin- and
      macrolide-non-susceptible isolates in European and Asian Russia. Resistance among
      macrolide-resistant isolates resulted mostly from the presence of erm(B) and
      mef(A), and from changes in L4; additionally, L22 mutations were common in
      isolates from Asian Russia. Non-susceptibility to quinolones was associated with
      mutations in parC and parE among European isolates. Asian Russian isolates had
      mutations in parC and gyrA, and alterations in parE were more common. There were
      substantial differences in non-susceptibility and mechanisms of resistance
      between pneumococci from Asian and European Russia, with orphanages appearing to
      be 'hot-spots' of resistance.

PMID- 16882291
TI  - Invasive pneumococcal disease among children in a health district of Barcelona:
      early impact of pneumococcal conjugate vaccine.
AB  - This study evaluated the impact of heptavalent pneumococcal conjugate vaccine
      (HPCV) on invasive pneumococcal disease (IPD) in children aged < or = 5 years in
      Barcelona, Spain. The incidence of IPD, vaccine uptake and prevalence of
      nasopharyngeal colonisation were analysed in two different periods: 1999-2001
      (pre-licence period), and 2002-2004 (post-licence period). In total, 121 cases of
      IPD were identified. The overall incidence of IPD decreased from 96.9
      cases/100,000 to 90.6 cases/100,000 (OR 0.93, 95% CI 0.69-1.26, p 0.71) between
      the two periods. The proportion of cases caused by non-vaccine-related serotypes
      (NVS) increased from 21% to 43.7% (OR 2.9, 95% CI 1.2-7, p 0.01). IPD was
      diagnosed in seven vaccinated children, six of whom were infected by NVS. There
      was a trend of diminishing prevalence of resistance to penicillin and macrolides
      in 2002-2004. The incidence of empyema increased from 1.7 to 8.5/100,000 (OR 4.5,
      95% CI 0.91-18, p 0.06). The rate of vaccination ranged from 4.8% to 34%. It was
      concluded that the rates of IPD in this area did not decrease following the
      introduction of HPCV. The low uptake of vaccine and the greater proportion of
      colonisation/infection by NVS probably explain these findings. A trend of
      increasing empyema was also apparent. A decrease in the prevalence of penicillin
      and macrolide resistance paralleled the progressive uptake of vaccine.

PMID- 16882292
TI  - The prevalence of penicillin-non-susceptible Streptococcus pneumoniae among
      children aged < 5 years correlates with the biannual epidemic activity of
      respiratory syncytial virus.
AB  - This study investigated whether the epidemiology of penicillin-non-susceptible
      pneumococci (PNSP) colonising small children correlated with the biannual
      epidemic activity of respiratory syncytial virus (RSV). Colonisation rates and
      the prevalence of PNSP among paediatric outpatients aged < 5 years was analysed
      between January 1998 and September 2003 using an established national
      surveillance network. Resistance trends were investigated using time-series
      analysis to assess the correlation with the biannual pattern of RSV infections
      and national sales of oral paediatric formulations of antibiotics and antibiotic
      prescriptions to children aged < 5 years for acute respiratory tract infections.
      PNSP rates exhibited a biannual cycle in phase with the biannual seasonal RSV
      epidemics (p < 0.05). Resistance rates were higher during the winter seasons of
      1998-1999 (20.1%), 2000-2001 (16.0%) and 2002-2003 (19.1%), compared with the
      winter seasons of 1997-1998 (8.2%), 1999-2000 (11.6%) and 2001-2002 (9.5%).
      Antibiotic sales and prescriptions showed regular peaks during each winter, with
      no significant correlation with the biannual pattern of RSV activity and seasonal
      trends of PNSP. RSV is an important determinant of the spread of PNSP and must be
      considered in strategies aimed at antimicrobial resistance control.

PMID- 16882293
TI  - Pathogenicity island markers in commensal and uropathogenic Escherichia coli
      isolates.
AB  - Uropathogenic isolates of Escherichia coli (UPEC) contain blocks of DNA, termed
      pathogenicity islands (PAIs), that contribute to their virulence. Two multiplex
      PCR assays were developed to detect eight PAI markers among 50 commensal E. coli
      and 100 UPEC isolates. In total, 40% of commensal isolates and 93% of UPEC
      carried PAIs. Despite this difference, the distribution of various PAIs showed
      the same pattern in both groups, with the most prevalent being PAI IV(536) (38%
      commensal vs. 89% UPEC), followed by PAI I(CFT073) (26% vs. 73%), PAI II(CFT073)
      (14% vs. 46%), PAI II(J96) (8% vs. 34%), PAI I(536) (8% vs. 33%) and PAI II(536)
      (4% vs. 20%). PAI III(536) was detected only in UPEC (2%), while PAI I(J96) was
      not detected in any isolate. Although the mean number of PAIs per isolate was
      higher among UPEC (2.97) than in commensal (0.98) isolates, there were no
      statistical differences among group B2 E. coli from the two origins; however,
      commensal isolates from groups D and B1 appeared to be less virulent than
      pathogenic isolates. Regardless of their phylogenetic group, nearly all the
      commensal and UPEC isolates with the same number of PAIs had the same PAI
      combinations. Although group B2 E. coli are uncommon among commensal intestinal
      flora, they are highly virulent when present, suggesting that the intestinal
      flora may act as a reservoir for bacteria that can cause urinary tract infection.

PMID- 16882294
TI  - Genetic relatedness between group B streptococci originating from bovine mastitis
      and a human group B Streptococcus type V cluster displaying an identical pulsed
      field gel electrophoresis pattern.
AB  - Twenty isolates of group B streptococcus (GBS) were recovered from the milk of
      cows with bovine mastitis on three farms located in the south and south-east of
      Brazil between 1987 and 1988. These isolates were characterised by molecular
      methods and compared with a collection of 103 human GBS isolates from colonised
      and infected patients in the same region between 1980 and 2003. Some of the
      bovine isolates shared identical or similar pulsed-field gel electrophoresis
      (PFGE) patterns with a PFGE clone of human GBS type V. In addition, these bovine
      and human isolates also possessed the same ribotype. Multilocus sequence typing
      (MLST) of representative isolates confirmed the genetic relationship between the
      human and bovine GBS isolates with identical PFGE patterns, which clustered in
      the same ST-26 clonal complex. These data support the hypothesis that some bovine
      GBS strains are related closely to human isolates and may infect humans, or vice
      versa. Further comparative genomic analyses of GBS isolates from bovine and human
      origins are required to investigate this hypothesis further.

PMID- 16882295
TI  - Evaluation of an internally controlled real-time PCR targeting the ospA gene for
      detection of Borrelia burgdorferi sensu lato DNA in cerebrospinal fluid.
AB  - This study reports the development and evaluation of an internally controlled
      real-time PCR targeting the ospA gene for detection of Borrelia burgdorferi sensu
      stricto, Borrelia garinii, Borrelia afzelii and Borrelia valaisiana. DNA was
      extracted using QIAamp DNA Blood Mini kit columns. DNA from 33 B. burgdorferi
      sensu lato strains reacted in the assay, whereas no reactivity was observed with
      DNA from four relapsing fever Borrelia spp., 11 unrelated spirochaetes, and 31
      unrelated microorganisms. The quantitative sensitivity of the assay was 1-10 fg
      of Borrelia DNA and one to five cultured Borrelia spirochaetes. Cerebrospinal
      fluid (CSF) specimens from 70 patients sent for routine testing for
      neuroborreliosis, and three CSF specimens containing B. garinii were also tested.
      Positive PCR results were obtained with all three culture-confirmed
      neuroborreliosis specimens, five of ten neuroborreliosis specimens with specific
      antibodies in CSF and pleocytosis, none of nine specimens from possible cases of
      early neuroborreliosis (antibodies in serum, CSF pleocytosis, no antibodies in
      CSF), one of 15 specimens from patients with active or past Lyme disease with
      neurological signs (antibodies in serum, no pleocytosis or antibodies in CSF),
      and none of 36 specimens from patients without Lyme borreliosis (no antibodies in
      serum or CSF). Overall, the real-time PCR assay enabled sensitive and specific
      detection of all B. burgdorferi sensu lato species tested. The PCR had a
      sensitivity of 50% in patients with neuroborreliosis. The main diagnostic role of
      the assay could be to confirm neuroborreliosis in patients for whom the diagnosis
      is doubtful.

PMID- 16882296
TI  - Comparison of the EUCAST-AFST broth dilution method with the CLSI reference broth
      dilution method (M38-A) for susceptibility testing of posaconazole and
      voriconazole against Aspergillus spp.
AB  - The susceptibilities of 40 clinical isolates of Aspergillus spp. (Aspergillus
      fumigatus, Aspergillus flavus, Aspergillus niger, Aspergillus terreus) were
      determined for posaconazole and voriconazole by the CLSI M38-A and EUCAST-AFST
      broth dilution methods. Where a discrepancy was observed between the methods, the
      EUCAST method tended to give higher MIC values. Overall, the level of agreement
      was 92.5% and the intra-class correlation coefficient was > 0.90.

PMID- 16882297
TI  - Determination of antimicrobial susceptibility patterns of Nocardia spp. from
      clinical specimens by Etest.
AB  - Susceptibilities to 11 antimicrobial agents were determined by Etest for 93
      Nocardia isolates from clinical specimens and 15 type strains belonging to
      different Nocardia spp. All isolates were susceptible to trimethoprim
      sulphamethoxazole, amikacin and linezolid, but susceptibilities of the various
      Nocardia spp. to beta-lactams, aminoglycosides, ciprofloxacin and clarithromycin
      varied markedly. Overall, there was a good correlation between the drug
      resistance patterns and the species identification established by conventional
      phenotypic tests and 16S rDNA sequencing. Among the different species
      encountered, Nocardia farcinica and Nocardia brasiliensis displayed the most
      multiresistant profiles, with resistance to imipenem occurring mainly among
      isolates of N. brasiliensis and Nocardia abscessus. The species variability in
      susceptibility profiles and the numerous recent taxonomic changes means that in
      vitro susceptibility tests may be a complementary tool for the identification of
      Nocardia isolates from human clinical specimens. Further studies on a larger
      number of species from more diverse geographical sources, including species that
      are found less commonly among clinical isolates, are required to validate and
      extend the results.

PMID- 16882298
TI  - Prevalence and estimated incidence of Toxoplasma infection among pregnant women
      in Poland: a decreasing trend in the younger population.
AB  - This study investigated the prevalence of specific Toxoplasma gondii IgG in
      pregnancy, the incidence of congenital toxoplasmosis and the prevalence trend of
      T. gondii infection among pregnant Polish women between 1998 and 2003. The study
      population comprised 4916 women who were admitted to the Polish Mother's Memorial
      Hospital Research Institute in Lodz. Their sera were tested for specific IgG and
      IgM antibodies to T. gondii, and the incidence of T. gondii infection was
      calculated from the increase in prevalence rates of IgG antibodies in various age
      groups. Specific IgG antibody was found in 41.3% (95% CI 39.9-42.7) of pregnant
      women, and the prevalence of IgG increased with age. The linear trend was
      significant (p <0.001), with an annual seroconversion rate of 0.7% (95% CI 0.004
      0.010). The risk of primary infection was estimated to be 0.5% for 9 months,
      i.e., an incidence of 5/1000 pregnancies. Assuming a 30% maternofetal
      transmission rate, 1.5/1000 neonates were infected in utero. Seroprevalence
      during the 6-year study period decreased from 45.4% in 1998 to 39.4% in 2003,
      with a yearly decline in prevalence of 1.0% (p 0.02). The most important
      contributory factor to this decline was the group of women aged 19-29 years,
      among whom seroprevalence decreased significantly (p 0.007). Specific IgM was
      found in 244 (4.9%) women.

PMID- 16882299
TI  - Molecular characterisation of Cryptosporidium isolates from humans in Slovenia.
AB  - Twenty-nine faecal specimens from Slovenian patients in which Cryptosporidium
      oocysts had been identified were studied. A fragment of the Cryptosporidium 18S
      rRNA gene and a fragment of the Cryptosporidium COWP gene were amplified by PCR
      and sequenced. Cryptosporidium parvum was identified in 26 of the 29 specimens,
      Cryptosporidium hominis in two, and Cryptosporidium cervine genotype in one. The
      fact that C. parvum, which is associated traditionally with animals, was
      identified in the majority of human faecal specimens suggests that
      cryptosporidiosis may have primarily a zoonotic origin in Slovenia.

PMID- 16882300
TI  - Epidemiological and clinical features of travel-associated cryptosporidiosis.
AB  - Data concerning the clinical and epidemiological features of travel-associated
      cryptosporidiosis are lacking. In order to investigate the impact of this disease
      on travellers' health, a retrospective study was conducted at the Institute of
      Tropical Medicine, Berlin. In total, 57 cryptosporidial infections were
      identified between 2000 and 2004, resulting in a prevalence of 2.9% in patients
      with travel-associated diarrhoea. Travel to south-central Asia, especially India,
      was associated with a higher prevalence of infection than was travel to other
      destinations. Clinically, the disease resembled giardiasis, but fever and
      arthralgias seemed to occur more frequently.

PMID- 16882301
TI  - Seroprevalence of human granulocytic anaplasmosis in Berlin/Brandenburg, Germany:
      an 8-year survey.
AB  - This study investigated the seroprevalence of antibodies against Anaplasma
      phagocytophilum in Berlin/Brandenburg, north-eastern Germany. During 1994-2001,
      422 sera from patients with proven tick-exposure (specimens with antibodies
      against Borrelia burgdorferi) were compared with 249 control sera. Using indirect
      fluorescent antibody testing, significantly more positive samples were detected
      among Borrelia antibody-positive specimens (4.5%, 95% CI 2.5-6.5%) than among
      controls (1.2%, 95% CI 0.5-1.9%; p < 0.05). While six (2.2%, 95% CI 1.3-3.1%)
      samples were positive among Borrelia antibody-positive sera between 1994 and
      1997, 13 (8.7%, 95% CI 6.9-10.5%) were positive between 1998 and 2001 (p < 0.01),
      indicating an uneven annual seroprevalence.

PMID- 16882303
TI  - Treatment of acute post-surgical infection of joint arthroplasty.
AB  - The best antibiotic regimen for acute prosthetic joint infection, treated without
      removal of the implant, has not been well-defined. This study describes the use
      of a protocol based on oral rifampicin combinations to treat 47 cases that were
      followed prospectively for a 2-year period. The regimen used most commonly was
      levofloxacin 500 mg/24 h plus rifampicin 600 mg/24 h for a mean duration of 2.7
      +/- 1 months. The cure rate was 76.9%, and the only independent risk-factor
      associated with treatment failure was infection caused by methicillin-resistant
      Staphylococcus aureus or Enterococcus spp. (OR 17.6, p 0.003). Overall, the
      results suggested that use of oral antibiotics, including rifampicin, for 2-3
      months was a good treatment option.

PMID- 16882302
TI  - Detection of Chlamydia trachomatis and herpes simplex virus type 1 or 2 in
      cervical samples in human papilloma virus (HPV)-positive and HPV-negative women.
AB  - This study investigated whether the prevalence of human papilloma virus (HPV) in
      association with Chlamydia trachomatis, herpes simplex virus (HSV)-1 and/or HSV-2
      was greater in high-grade than in low-grade or control cervical biopsy specimens.
      HPV-positive (n = 86) and HPV-negative (n = 213) women were screened for HPV, HSV
      and C. trachomatis by PCR. The most common HPV genotypes were HPV-16, HPV-6 and
      HPV-33; mixed HPV infection (n = 12) was also seen. A higher prevalence of C.
      trachomatis, HSV-1 and HSV-2 was found in HPV-positive samples. High-risk HPV
      genotypes and combined HPV + C. trachomatis or HPV + HSV-1, but not HSV-2,
      infections were associated with a greater risk of developing cervical carcinoma.

PMID- 16882304
TI  - Clinical significance of isolated Staphylococcus aureus central venous catheter
      tip cultures.
AB  - This retrospective cohort study examined the clinical significance of isolated
      Staphylococcus aureus central venous catheter (CVC) tip cultures (i.e., positive
      tip cultures without concomitant positive blood cultures). Subsequent S. aureus
      bacteraemia was found in nine (12%) of 77 patients at a median time of 4 days
      after CVC removal. A high co-morbidity score and no effective antibiotic
      treatment within 48 h of CVC removal were independent risk-factors for septic
      complications following multivariate analysis. A matched case-control study that
      compared the above cohort with patients with CVC tip cultures negative for S.
      aureus supported the significance of these findings.

PMID- 16882305
TI  - Evaluation of differential gene expression in susceptible and resistant clinical
      isolates of Klebsiella pneumoniae by DNA microarray analysis.
AB  - DNA microarray technology was used to evaluate differential gene expression in a
      susceptible Klebsiella pneumoniae isolate and a resistant clinical derivative.
      Nineteen genes were up-regulated in the resistant isolate when compared with the
      susceptible isolate. An ABC transporter-related gene, ycjV, was strongly over
      expressed, suggesting the existence of a novel active efflux mechanism.
      Approximately half of the up-regulated genes coded for ribosomal proteins, or
      proteins involved in tRNA metabolism. Among 33 downregulated genes, almost one
      third were related to nitrogen metabolism. A possible role of fitness in the
      development of antimicrobial resistance is suggested.

PMID- 16882306
TI  - Emergence of carbapenem-hydrolysing metallo-beta-lactamase VIM-1 in Pseudomonas
      aeruginosa isolates in France.

PMID- 16882308
TI  - Invasive pneumococcal disease in adults in North-Rhine Westphalia, Germany.

PMID- 16882309
TI  - Use of molecular techniques for epidemiological typing of rapidly growing
      mycobacteria.

PMID- 16882311
TI  - Chronic oral nicotine treatment protects against striatal degeneration in MPTP
      treated primates.
AB  - The present studies were done to investigate the effect of long-term nicotine
      treatment against nigrostriatal damage in non-human primates. Monkeys were
      administered nicotine in drinking water for 6 months to provide chronic but
      intermittent delivery as with smoking. Plasma nicotine levels ranged from 10 to
      15 ng/mL, which were within the range in cigarette smokers. Animals were then
      lesioned with low doses of the dopaminergic neurotoxin MPTP for several months
      while nicotine was continued. The results showed that levels of striatal tyrosine
      hydroxylase, dopamine transporter, vesicular monoamine transporter, dopamine and
      nicotinic receptors were greater in nicotine-treated MPTP-lesioned primates than
      in lesioned animals not receiving nicotine. Nicotine had no effect in unlesioned
      animals. Monoamine oxidase activity was similar in unlesioned and lesioned
      animals treated with or without nicotine, suggesting that nicotine did not exert
      its effects through changes in MPTP or dopamine metabolism. MPTP-induced cell
      loss in the substantia nigra was unaffected by nicotine treatment, indicating
      that nicotine acts at the striatal level to restore/maintain dopaminergic
      function. These data further support the possibility that nicotine contributes to
      the lower incidence of Parkinson's disease in smokers.

PMID- 16882313
TI  - A kinase-focused compound collection: compilation and screening strategy.
AB  - Lead identification by high-throughput screening of large compound libraries has
      been supplemented with virtual screening and focused compound libraries. To
      complement existing approaches for lead identification at Biogen Idec, a kinase
      focused compound collection was designed, developed and validated. Two strategies
      were adopted to populate the compound collection: a ligand shape-based virtual
      screening and a receptor-based approach (structural interaction fingerprint).
      Compounds selected with the two approaches were cherry-picked from an existing
      high-throughput screening compound library, ordered from suppliers and
      supplemented with specific medicinal compounds from internal programs. Promising
      hits and leads have been generated from the kinase-focused compound collection
      against multiple kinase targets. The principle of the collection design and
      screening strategy was validated and the use of the kinase-focused compound
      collection for lead identification has been added to existing strategies.

PMID- 16882314
TI  - Hierarchical strategy for identifying active chemotype classes in compound
      databases.
AB  - A general methodology is presented for analyzing patterns of activity in compound
      databases, which is based on the use of structural chemotypes and provides a
      focused, hierarchical classification of active compounds. Each node in the
      hierarchical tree corresponds to a specific chemotype and is labeled by a unique
      code or identifier. All chemotypes at a given level of the hierarchy define
      equivalence classes, and those of higher structural resolution have a strict
      parent-child (i.e. subset) relationship to those of lower resolution. Active
      chemotypes contain a relatively high proportion of actives and are characterized
      through the use of enrichment plots. These plots show the relationship of
      occupancy to activity enrichment for a set of chemotypes at a given level of
      structural resolution. Paths through the hierarchy from chemotypes of lower to
      those of higher structural resolution (e.g. reduced cyclic system skeletons -->
      cyclic system skeletons --> cyclic systems --> complete molecules) are unique.
      Unique paths in the hierarchy that only pass through active chemotypes are called
      chains or paths of actives. These chains provide links for identifying
      structurally related active compounds at increasing levels of structural
      resolution. Analysis of actives can also be carried out at any specific level of
      structural resolution deemed appropriate by the investigator. Chemotype codes can
      be used to search compound databases for new molecules possessing these codes or
      sets of hierarchically related codes. An example, based on the NCI AIDS database,
      is presented that illustrates the general approach and provides a more detailed
      description of several interesting classes of active chemotypes and their inter
      relationships.

PMID- 16882315
TI  - Searching for new antimalarial therapeutics amongst known drugs.
AB  - The need to discover and develop new antimalarial therapeutics is overwhelming.
      The annual mortality attributed to malaria, currently approximately 2.5 million,
      is increasing due primarily to widespread resistance to currently used drugs. One
      strategy to identify new treatment alternatives for malaria is to examine
      libraries of diverse compounds for the possible identification of novel
      scaffolds. Beginning with libraries of drug or drug-like compounds is an ideal
      starting point because, in the case of approved drugs, substantial
      pharmacokinetic and toxicologic data should be available for each compound
      series. We have employed a high-throughput screen of the MicroSource Spectrum and
      Killer Collections, a library of known drugs, bioactive compounds, and natural
      products. Our screening assay identifies compounds that inhibit growth of
      Plasmodium falciparum cultured in human erythrocytes. We have identified 36 novel
      inhibitors of P. falciparum, of which 19 are therapeutics, and five of these
      drugs exhibit effective 50% inhibitory concentrations within similar ranges to
      therapeutic serum concentrations for their recently indicated uses: propafenone,
      thioridazine, chlorprothixene, perhexiline, and azlocillin. The findings we
      report here indicate that this is an effective strategy to identify novel
      scaffolds and therefore aid in antimalarial drug discovery efforts.

PMID- 16882317
TI  - Design of a peptibody consisting of the antimicrobial peptide dhvar5 and a llama
      variable heavy-chain antibody fragment.
AB  - Immunoconjugates have been widely studied as potential therapeutics for
      infectious diseases to direct unspecific antimicrobials to pathogens. In this
      study, the recombinant approach was used for expression of the immunoconjugate
      composed of the variable domain of a llama heavy-chain antibody (VHH) against
      Streptococcus mutans and dhvar5, a synthetic antimicrobial peptide. Before
      cloning, the impact of the elongation of the peptide termini on its biological
      activity was evaluated by chemical synthesis of the N- or C-termini extended
      dhvar5 peptides. As the elongation of the C-terminus had a greater influence on
      decline of the antimicrobial activity, the N-terminal fusion was designed. To
      promote in vivo release of the active peptide, a factor Xa cleavage site was
      inserted between VHH and dhvar5. Propagation of transformed Escherichia coli with
      the constructed plasmid was only possible in the absence of isopropyl beta-D
      thiogalactoside (IPTG). Although these data demonstrate that the diminished
      antimicrobial activity of dhvar5 by the N-terminal fusion to VHH was not
      sufficient for the protection of the bacterial host cells against the peptide
      lethal effect, an insight into propeptides biological activities may be
      beneficial not only for new and more successful rearrangement of the VHH-dhvar5
      immunoconjugate construct, but also design of the other recombinant molecules
      composed of peptides toxic to host cells.

PMID- 16882316
TI  - Structural evaluation of a novel pro-apoptotic peptide coupled to CNGRC tumor
      homing sequence by NMR.
AB  - Hunter-killer peptides (HKPs) are synthetic peptides that target specific cell
      types for apoptosis. These studies report functional and structural
      characteristics of HKP9, an hunter-killer peptide that specifically targets tumor
      vasculature with a new apoptotic sequence. Vesicle leakage experiments were
      performed as a model for membrane perturbing activity. Placement of the homing
      sequence reduces both cell toxicity and vesicle leakage activity. NMR studies
      elucidate the conformation and orientation of HKP9 in micelles. The positively
      charged end of the HKP9 killing sequence is solvent exposed; however, the central
      portion of the peptide is helical and buried in dodecylphosphorylcholine
      micelles. The homing sequence is less solvent exposed than in a previously
      reported tumor-homing peptide. The results suggest that solvent accessibility of
      the homing sequence should be considered in design of future peptides.

PMID- 16882318
TI  - Synthesis and pharmacological activity of 2-(substituted)-3-{2-[(4-phenyl-4
      cyano)piperidino]ethyl}-1,3-thiazolidin-4-ones.
AB  - Loperamide is a well-known peripherally acting opiate used for the treatment of
      diarrhoea. To gain more knowledge on the structure-activity relationships of
      antidiarrhoeal drugs and to develop new active molecules, a series of aryl-cyano
      piperidinoalkyl-thiazolidinones related to Loperamide was synthesized and
      screened for antidiarrhoeal activity in mice by castor oil test. To characterize
      the potency and toxicity of the synthesized compounds ED50 and LD50 values were
      also determined. The thiazolidinones 2-6 displayed antidiarrhoeal activity at
      doses ranging between 15 and 82 mg/kg. Although the results show that the
      synthesized compounds are 15- to 80-fold less active respect to the reference
      compound, Loperamide, they are much less toxic (> or = 1000 mg/kg and 108.9
      mg/kg, respectively). Besides, to evaluate the involvement of opioid receptors in
      antidiarrhoeal activity, Naloxone was administered prior to test the 2-phenyl-3
      {2-[(4-phenyl-4-cyano)piperidino]ethyl}-1,3-thiazolidin-4-one (2), the more
      active compound of this series. The results obtained by this study, suggest that
      the antidiarrhoeal activity of this series of thiazolidinone derivatives could
      involve the opioid receptors.

PMID- 16882319
TI  - Design and synthesis of an alpha1a-adrenergic receptor subtype-selective
      antagonist from BE2254.
AB  - An alpha1a-adrenoceptor-selective antagonist has the potential to be a new benign
      prostatic hyperplasia drug with reduced side-effects. Modification of the non
      selective antagonist BE2254 led to the development of a series of tetralin
      analogs. Evaluation of these compounds in cloned human alpha1-adrenoceptors
      resulted in the discovery of an analog that showed selectivity toward the human
      alpha1a-adrenergic receptor subtype. The compound also showed moderate potency to
      block human prostate muscle contraction.

PMID- 16882320
TI  - Dissecting the functions of proteins and pathways using chemically induced
      dimerization.

PMID- 16882324
TI  - Antimicrobial susceptibility of Helicobacter pylori strains in a random adult
      Swedish population.
AB  - BACKGROUND AND AIM: Antimicrobial resistance in Helicobacter pylori is a growing
      problem and has become an important factor leading to eradication failure.
      Information on antimicrobial susceptibility is important for selection of an
      optimum treatment regimen. The resistance rate in a random population has not
      been studied previously. METHODS: A random Swedish population sample (n = 3000,
      age 20-1 years) was surveyed using a mailed validated questionnaire assessing
      gastrointestinal symptoms (response rate of 74%). One-third of the responders was
      invited, in random order, and accepted an esophagogastroduodenoscopy with
      biopsies for H. pylori culture and histology. Subjects were not treated for their
      H. pylori infection but a minimum inhibitory concentration of metronidazole,
      clarithromycin, amoxicillin, and tetracycline for the H. pylori isolates (n =
      333) was determined by agar dilution. Prescribed antibiotic in the area was
      recorded. RESULTS: Irrespective of symptomatology, 16.2% of the isolated H.
      pylori strains were resistant to metronidazole, 1.5% to clarithromycin, 0% to
      amoxicillin, and 0.3% to tetracycline. The antibiotic consumption was low from an
      international perspective. CONCLUSION: The resistance to the antibiotics was
      lower than expected from patient sample studies, especially for clarithromycin,
      most probably due to a restrictive prescription policy in the area. Introduction
      of a test-and-treat strategy in Sweden would only marginally affect the usage of
      clarithromycin.

PMID- 16882323
TI  - Helicobacter pylori eradication therapy on histologic change in the distal
      esophagus.
AB  - BACKGROUND: Although cases of reflux esophagitis (RE) developing after treatment
      to eradicate Helicobacter pylori have been discussed in some detail, no reports
      are available concerning the histologic examination of RE both before and after
      eradication therapy. MATERIALS AND METHODS: Sixty-one patients and 111 specimens
      were investigated using endoscopic and histologic techniques. The histologic
      findings including basal zone height, papillar height, Ki-67 labeling index, and
      COX-2 expression before and after treatment for H. pylori infection were compared
      with those in normal controls and patients with endoscopic RE. RESULTS: Twelve
      months after eradication therapy, the incidence of newly developed endoscopic RE
      was 20% (5/25). Basal zone height and papillar height had increased at 1 month,
      but had returned to pretreatment levels after 12 months of eradication therapy.
      The Ki-67 labeling index was significantly increased 1 and 12 months after
      eradication therapy compared to values before treatment. COX-2 expression
      gradually increased after the treatment. The phenomena linked to esophagitis
      appeared after eradication therapy. However, the severity and extent of these
      signs were not so high after the treatment of H. pylori than those in patients
      with overt reflux esophagitis. Focusing on the patients with hiatal hernia,
      papillar height and Ki-67 labeling index increased significantly after
      eradication therapy, values being almost the same as those in the patients with
      endoscopic RE. CONCLUSIONS: Hiatal hernia plays an important role in the possible
      occurrence of hidden RE after treatment for a H. pylori infection.

PMID- 16882325
TI  - Efficacy and safety of rabeprazole, amoxicillin, and gatifloxacin after treatment
      failure of initial Helicobacter pylori eradication.
AB  - OBJECTIVES: To evaluate the efficacy of a 7-day regimen of gatifloxacin (400 mg
      daily), amoxicillin (1 g twice a day), and rabeprazole (20 mg twice a day) in the
      secondary eradication of Helicobacter pylori infection. METHODS: Eligible
      patients with persistent infection following one or more conventional
      clarithromycin-containing triple therapies were enrolled in this open-label
      trial. Eradication of infection was documented by (14)C-urea breath test a
      minimum of 4 weeks after therapy and 2 weeks off any acid suppressive therapy.
      Culture of H. pylori and in vitro susceptibility testing to amoxicillin,
      clarithromycin, and gatifloxacin was done in cases of failed eradication.
      RESULTS: A total of 45 patients (22 females:23 males; mean age 44.5 +/- 13 years)
      were enrolled. Eradication occurred in 38 patients [both per-protocol (PP) and
      intention-to-treat analysis: 84.4%; 95% CI: 74-95%]. No significant adverse
      effects were reported. In vitro susceptibility testing showed no secondary
      resistance to gatifloxacin or amoxicillin in any of the seven nonresponders.
      Smoking, age, and sex were not predictors of potential eradication failure.
      CONCLUSIONS: A 7-day regimen of gatifloxacin, rabeprazole, and amoxicillin is
      effective after failed eradication therapy for H. pylori and does not appear to
      result in secondary resistance. This combination is simple, well tolerated, and
      may lead to higher compliance and lower costs.

PMID- 16882326
TI  - Role of the preliminary susceptibility testing for initial and after failed
      therapy of Helicobacter pylori infection with levofloxacin, amoxicillin, and
      esomeprazole.
AB  - BACKGROUND: Levofloxacin has been proposed as an alternative to classic therapy
      in secondary resistance to Helicobacter pylori. AIM: To evaluate primary and
      secondary resistance of H. pylori to levofloxacin, and to test the role of
      susceptibility test on the efficacy of levofloxacin-based triple therapy.
      METHODS: Eighty consecutive dyspeptic patients with positive (13)C-urea breath
      test never treated were randomly allocated into group A(1) (40 patients) and
      group B(1) (39 patients). Eighty-three patients already treated unsuccessfully
      with positive (13)C-urea breath test were divided into group A(2) (51 patients)
      and group B(2) (32 patients). Patients in group A(1) and group A(2) underwent
      upper gastrointestinal endoscopy for H. pylori susceptibility test to
      amoxicillin, clarithromycin, tinidazole, rifabutin, and levofloxacin. These
      patients were treated with levofloxacin (500 mg b.i.d.), amoxicillin (1 g b.i.d.)
      and esomeprazole (20 mg b.i.d.) for 10 days if sensitive to these two
      antibiotics. If H. pylori was found resistant to amoxicillin and/or levofloxacin
      the treatment was based on the indications of the susceptibility test. Patients
      in group B(1) and group B(2) were treated empirically with levofloxacin,
      amoxicillin, and esomeprazole at the same dose and duration as group A. All
      patients underwent (13)C-urea breath test 2 months after the end of therapy.
      RESULTS: The antibiotic resistance of H. pylori strains in group A(1) and group
      A(2) was (%): amoxicillin: 2.4, 10; clarithromycin: 21.9, 43.1; tinidazole: 31.7,
      70; rifabutin: 2.4, 4; and levofloxacin: 9.7, 12.2, respectively. In group A(1)
      with susceptibility test-driven therapy, eradication was 97.2%, and in group B(1)
      with empirical treatment, 94.1% (n.s.). In group A(2) with susceptibility test,
      eradication was 97.5%, whereas in group B(2) with empirical treatment 81.2% (p <
      .01). CONCLUSION: Primary and secondary resistance of H. pylori to levofloxacin
      is approximately 10% of the tested strains. The susceptibility test does not
      influence therapeutic outcome of triple therapy with amoxicillin and levofloxacin
      in patients never treated, while it is determinant for patients who were
      previously treated without success.

PMID- 16882327
TI  - Primary levofloxacin resistance and gyrA/B mutations among Helicobacter pylori in
      Japan.
AB  - BACKGROUND: Recent years have witnessed a decrease in the rate of Helicobacter
      pylori eradication due to antimicrobial resistance, clarithromycin or
      metronidazole resistance in particular. As one of the alternatives to the
      standard regimens, levofloxacin-containing therapy has been considered a
      promising regimen. Nevertheless, there is a little information concerning the
      prevalence of levofloxacin resistance and this resistance mechanism. MATERIALS
      AND METHODS: Levofloxacin susceptibility was examined using E-test in 507 H.
      pylori strains clinically isolated in Japan from 2001 to 2004. Mutation patterns
      in the quinolone resistance-determining regions of the gyrA and gyrB genes were
      evaluated, performing direct sequencing of 68 levofloxacin-resistant and 50
      susceptible strains. RESULTS: Primary levofloxacin resistance was found in 76
      (15.0%) strains. Fifty-seven (83.8%) of 68 levofloxacin-resistant strains
      analyzed had point mutations in gyrA at Asn-87 or Asp-91, while seven (14.0%) of
      50 susceptible strains had gyrA mutations. There was a significant difference in
      the occurrence of gyrA mutations between levofloxacin-resistant and -susceptible
      strains (p < .001). In levofloxacin-resistant strains, the occurrence of gyrA
      mutations at Asn-87 was most common regardless of minimal inhibitory
      concentration levels, and that of gyrA mutations at Asp-91 tended to be
      associated with low-level resistance. A double gyrA mutation at Asn-87 and Asp-91
      might have an additional impact. As for gyrB, three (4.4%) of 68 levofloxacin
      resistant strains with no susceptible strains had mutations. CONCLUSIONS: Primary
      levofloxacin resistance was common in Japan and primarily related to gyrA
      mutations at Asn-87 and Asp-91.

PMID- 16882328
TI  - A prospective study for the association of Helicobacter pylori infection to a
      multidimensional measure for recurrent abdominal pain in children.
AB  - BACKGROUND: There is a controversial association between Helicobacter pylori
      infection and recurrent abdominal pain (RAP) in childhood and inconsistent
      information on specific symptomatology of the infection. AIMS: To examine the
      prevalence of H. pylori infection among children with RAP compared to
      asymptomatic children. METHODS: Two prospective studies were conducted. The first
      study enrolled 223 children diagnosed with RAP from two pediatric
      gastroenterology clinics in Houston, Texas. Children were qualified if they were
      identified by their physician as having RAP. A new multidimensional measure for
      RAP (MM-RAP) consisting of four scales (pain intensity scale, symptoms scale,
      disability scale, and satisfaction scale) was administered to each child/parent.
      The second study enrolled 330 asymptomatic children from the same community who
      did not have any upper gastrointestinal symptoms. Symptomatic and asymptomatic
      children underwent (13)C-urea breath testing. RESULTS: In the first study, the
      prevalence of H. pylori in children with RAP was 11% and fell with age from 20%
      at age < or = 5 years to 7% for children > 10 years (OR = 2.7, 95% CI = 0.7
      11.2). There was no association between the mother's educational level and H.
      pylori prevalence; (12% among children whose mothers completed college versus 11%
      among those who had elementary school, p = .8). No relationship was found between
      H. pylori and mean scores of the RAP scales. In the second study, the prevalence
      of H. pylori in asymptomatic children was 17% and increased with age from 11% for
      children < or = 5 years to 40% for children > 10 years (OR = 5.4, 95% CI = 2.0
      13.8). The mother's educational level was inversely correlated with H. pylori (OR
      = 3.0, 95% CI = 2.2-6.1, p < .01). CONCLUSIONS: The epidemiologic patterns of H.
      pylori infection differed significantly between symptomatic and asymptomatic
      children. Younger children suffering from RAP are more likely to be infected with
      H. pylori than older children with the same complaint, suggesting that early
      acquisition may manifest in symptoms that lead to clinic visits.

PMID- 16882329
TI  - Gastric epithelial expression of macrophage migration inhibitory factor is not
      altered by Helicobacter pylori infection in humans.
AB  - BACKGROUND: Recent reports have shown an upregulation of macrophage migration
      inhibitory factor (MIF) during gastric ulcer development in a rat model and
      elevated counts of MIF-positive cells in biopsies from Helicobacter pylori
      infected patients. H. pylori infection is a proven cofactor in humans causing
      gastritis and gastric ulcers. The aim of this study was to characterize MIF
      expression in human gastric epithelial cells in response to H. pylori. METHODS:
      MIF mRNA and MIF protein expression was detected in human gastric epithelial cell
      lines after stimulation with proinflammatory cytokines or infection with H.
      pylori (cagA+/vacA+) using real-time reverse transcriptase-polymerase and enzyme
      linked immunosorbent assay. Interleukin-8 secretion was measured as positive
      control. MIF mRNA and MIF protein expression was assessed in H. pylori-positive
      and -negative human gastric biopsy samples. RESULTS: While interleukin-8 mRNA
      expression and interleukin-8 secretion were upregulated in gastric epithelial
      cells in vitro after H. pylori infection, no changes in MIF mRNA expression and
      MIF secretion could be detected. We found no significant differences in MIF
      expression in total RNA extracted from gastric biopsy tissue when comparing H.
      pylori-positive to control patients. Likewise, MIF protein expression in gastric
      epithelium was unaffected by H. pylori infection as compared to uninfected
      tissue. CONCLUSIONS: While an increased MIF expression and positive effects of
      MIF blockade in ulcer healing have been shown in a rodent model and elevated
      numbers of MIF-positive cells have been found in H. pylori-infected human tissue,
      we herein could not confirm any differences in human gastric epithelial MIF
      expression and secretion after H. pylori infection in vitro and in vivo.

PMID- 16882330
TI  - Production of reactive oxygen species in peripheral blood is increased in
      individuals with Helicobacter pylori infection and decreased after its
      eradication.
AB  - BACKGROUND: Helicobacter pylori infection has been reported to cause
      gastroduodenal ulcer, mucosa-associated lymphoid tissue lymphoma, and gastric
      cancer. Recent studies have suggested that H. pylori infection may also associate
      with other diseases, including hematologic and dermatologic disorders, and
      cardiovascular injury, by unknown mechanisms. METHODS: Production of reactive
      oxygen species (ROS) was determined in peripheral blood samples from 86 patients
      (34 H. pylori-negative and 52 H. pylori-positive subjects) using a highly
      sensitive chemiluminescence probe, L-012 (8-amino-5-chloro-7-phenylpyrido(3,4-d)
      pyridazine-1 and 4 (2H, 3H) dione). Eleven H. pylori-positive individuals were
      also analyzed their ROS production in peripheral blood after H. pylori
      eradication. RESULTS: ROS production was significantly higher in individuals with
      H. pylori infection than in those without infection. Enhanced production of ROS
      was decreased significantly after eradication of H. pylori. No correlation was
      found between the extent of ROS production and sex, age, smoking status, alcohol
      ingestion, use of medications, or serum level of C-reactive protein. CONCLUSION:
      These findings suggest that ROS production was enhanced in peripheral blood by H.
      pylori infection. Chemiluminescence analysis of blood samples using L-012 permits
      evaluation of systemic oxidative stress in patients with H. pylori infection.

PMID- 16882331
TI  - Demonstration and characterization of mutations induced by Helicobacter pylori
      organisms in gastric epithelial cells.
AB  - BACKGROUND: Helicobacter pylori gastritis increases gastric cancer risk.
      Microsatellite instability-type mutations are secondary to deficient DNA mismatch
      repair. H. pylori gastritis is more frequent in patients with microsatellite
      instability-positive gastric cancers, and H. pylori organisms independently of
      inflammation can reduce DNA mismatch repair protein levels, raising the
      hypothesis that H. pylori organisms might lead to mutagenesis during infection.
      MATERIALS AND METHODS: Mutations were detected using a green fluorescent protein
      reporter vector (pEGFP-CA13). Gastric cancer AGS cells transfected with pEGFP
      CA13 were cocultured with H. pylori or Escherichia coli. The numbers of green
      fluorescent protein (GFP)-positive cells were determined, and GFP, hMSH2, and
      hMLH1 protein levels were measured by Western blot. The effect of H. pylori on
      CpG methylation status of hMLH1 was determined by methylation-specific polymerase
      chain reaction. RESULTS: GFP levels and GFP-positive cell numbers in AGS cells
      cocultured with H. pylori significantly increased, as the levels of hMLH1 and
      hMSH2 dropped. H. pylori cocultures induced low-level CpG methylation of the
      hMLH1 promoter. Sequence analysis of cells cocultured with H. pylori showed an
      increased number of frameshift mutations and point mutations as compared to cells
      not cocultured with H. pylori (p = .03 and p = .001, respectively). CONCLUSIONS:
      This is the first report showing that H. pylori bacteria may lead to accumulation
      of genomic mutations, independently of underlying inflammation. This is
      associated with reduced DNA mismatch repair, and is at least in part associated
      with CpG methylation of the hMLH1 promoter. These data support the notion that H.
      pylori-induced mutations and epigenetic alterations in gastric epithelial cells
      during chronic gastritis may contribute to an increased risk of gastric cancer
      associated with H. pylori infection.

PMID- 16882332
TI  - Bioinformatic analysis of Helicobacter pylori XGPRTase: a potential therapeutic
      target.
AB  - BACKGROUND: Xanthine-guanine phosphoribosyltransferase (XGPRTase) is an enzyme of
      purine nucleotide salvage synthesis. The gpt gene of Helicobacter pylori has been
      annotated as encoding an XGPRTase and proposed as essential for survival of the
      bacterium in vitro. The aims of this work were to investigate the structure of H.
      pylori XGPRTase and to compare the key features of the enzyme to other
      phosphoribosyltransferases employing computational, modelling, and bioinformatic
      tools. MATERIALS AND METHODS: XGPRTase activity was measured in the cytosolic
      fraction of H. pylori by (31)P-nuclear magnetic resonance spectroscopy, and also
      in recombinant XGPRTase produced by a cell-free expression system. Bioinformatics
      was employed to analyze the phylogeny of XGPRTase, and a structural model of the
      XGPRTase was built using threading techniques. The observed interactions of
      purine phosphoribosyltransferases with immucillin-GP were used to study the
      theoretical interactions of H. pylori XGPRTase with this transition-state analog.
      RESULTS: It was demonstrated that the gpt gene of H. pylori encodes a functional
      XGPRTase enzyme. Analyses of the XGPRTase sequence showed that the enzyme is
      significantly divergent from equivalent mammalian enzymes. Modelling served to
      identify specific features of the enzyme and key residues involved in catalysis.
      CONCLUSIONS: The H. pylori XGPRTase is structurally similar to other
      phosphoribosyltransferase enzymes, but there were significant differences between
      the hood domain of H. pylori XGPRTase and other purine salvage
      phosphoribosyltransferases. Significant differences were found between the
      interactions of the H. pylori and human enzymes with a purine
      phosphoribosyltransferase inhibitor.

PMID- 16882333
TI  - Is Helicobacter pylori a true microaerophile?
AB  - BACKGROUND: There is no general consensus about the specific oxygen and carbon
      dioxide requirements of the human pathogen Helicobacter pylori. This bacterium is
      considered a microaerophile and consequently, it is grown under atmospheres at
      oxygen tensions 5-19% and carbon dioxide tensions 5-10%, both for clinical and
      basic and applied research purposes. The current study compared the growth of H.
      pylori in vitro, under various gas atmospheres, and determined some specific
      changes in the physiology of bacteria grown under different oxygen partial
      pressures. METHODS: Measurements of bacterial growth under various conditions
      were carried out employing classical solid and liquid culture techniques.
      Enzymatic activities were measured using spectrophotometric assays. RESULTS: H.
      pylori and all the other Helicobacter spp. tested had an absolute requirement for
      elevated carbon dioxide concentrations in the growth atmosphere. In contrast with
      other Helicobacter spp., H. pylori can tolerate elevated oxygen tensions when
      grown at high bacterial concentrations. Under 5% CO(2), the bacterium showed
      similar growth in liquid cultures under oxygen tensions from microaerobic (< 5%)
      to fully aerobic (21%) at cell densities higher than 5 x 10(5) cfu/ml for media
      supplemented with horse serum and 5 x 10(7) cfu/ml for media supplemented with
      beta-cyclodextrin. Evidence that changes occurred in the physiology of H. pylori
      was obtained by comparing the activities of ferredoxin:NADH (nicotinamide adenine
      dinucleotide) oxidoreductases of bacteria grown under microaerobic and aerobic
      atmospheres. CONCLUSIONS: H. pylori is a capnophile able to grow equally well in
      vitro under microaerobic or aerobic conditions at high bacterial concentrations,
      and behaved like oxygen-sensitive microaerophiles at low cell densities. Some
      characteristics of H. pylori cells grown in vitro under microaerobic conditions
      appeared to mimic better the physiology of organisms grown in their natural niche
      in the human stomach.

PMID- 16882334
TI  - Hypermutation and treatment of Helicobacter pylori.

PMID- 16882337
TI  - Reappraisal of Pseudomonas aeruginosa hospital-acquired pneumonia mortality in
      the era of metallo-beta-lactamase-mediated multidrug resistance: a prospective
      observational study.
AB  - INTRODUCTION: Hospital-acquired pneumonia (HAP) due to Pseudomonas aeruginosa is
      associated with high mortality rates. The metallo-beta-lactamases (MBLs) are
      emerging enzymes that hydrolyze virtually all beta-lactams. We aimed to assess P.
      aeruginosa HAP mortality in a setting of high-rate MBL production METHODS: A
      prospective cohort study was performed at two tertiary-care teaching hospitals. A
      logistic regression model was constructed to identify risk factors for 30-day
      mortality. RESULTS: One-hundred and fifty patients with P. aeruginosa HAP were
      evaluated. The 30-day mortality was 37.3% (56 of 150): 57.1% (24 of 42) and 29.6%
      (32 of 108) for patients with HAP by MBL-producing P. aeruginosa and by non-MBL
      producing P. aeruginosa, respectively (relative risk, 1.93; 95% confidence
      interval (CI), 1.30-2.85). The logistic regression model identified a higher
      Charlson comorbidity score (odds ratio, 1.21; 95% CI, 1.04-1.41), presentation
      with severe sepsis or septic shock (odds ratio, 3.17; 95% CI, 1.30-7.72),
      ventilator-associated pneumonia (odds ratio, 2.92; 95% CI, 1.18-7.21), and
      appropriate therapy (odds ratio, 0.24; 95% CI, 0.10-0.61) as independent factors
      for 30-day mortality. MBL production was not statistically significant in the
      final model. CONCLUSION: MBL-producing P. aeruginosa HAP resulted in higher
      mortality rates, particularly in patients with ventilator-associated pneumonia,
      most probably related to the less frequent institution of appropriate
      antimicrobial therapy. Therapeutic approaches should be reviewed at institutions
      with a high prevalence of MBL.

PMID- 16882338
TI  - Rapid detection of pneumothorax by ultrasonography in patients with multiple
      trauma.
AB  - INTRODUCTION: Early detection of pneumothorax in multiple trauma patients is
      critically important. It can be argued that the efficacy of ultrasonography (US)
      for detection of pneumothorax is enhanced if it is performed and interpreted
      directly by the clinician in charge of the patients. The aim of this study was to
      assess the ability of emergency department clinicians to perform bedside US to
      detect and assess the size of the pneumothorax in patients with multiple trauma.
      METHODS: Over a 14 month period, patients with multiple trauma treated in the
      emergency department were enrolled in this prospective study. Bedside US was
      performed by emergency department clinicians in charge of the patients. Portable
      supine chest radiography (CXR) and computed tomography (CT) were obtained within
      an interval of three hours. Using CT and chest drain as the gold standard, the
      diagnostic efficacy of US and CXR for the detection of pneumothorax, defined as
      rapidity and accuracy (sensitivity, specificity, positive predictive value,
      negative predictive value), were compared. The size of the pneumothorax (small,
      medium and large) determined by US was also compared to that determined by CT.
      RESULTS: Of 135 patients (injury severity score = 29.1 +/- 12.4) included in the
      study, 83 received mechanical ventilation. The time needed for diagnosis of
      pneumothorax was significantly shorter with US compared to CXR (2.3 +/- 2.9
      versus 19.9 +/- 10.3 minutes, p < 0.001). CT and chest drain confirmed 29 cases
      of pneumothorax (21.5%). The diagnostic sensitivity, specificity, positive and
      negative predictive values and accuracy for US and radiography were 86.2% versus
      27.6% (p < 0.001), 97.2% versus 100% (not significant), 89.3% versus 100% (not
      significant), 96.3% versus 83.5% (p = 0.002), and 94.8% versus 84.4% (p = 0.005),
      respectively. US was highly consistent with CT in determining the size of
      pneumothorax (Kappa = 0.669, p < 0.001). CONCLUSION: Bedside clinician-performed
      US provides a reliable tool and has the advantages of being simple and rapid and
      having higher sensitivity and accuracy compared to chest radiography for the
      detection of pneumothorax in patients with multiple trauma.

PMID- 16882339
TI  - Pediatric defibrillation after cardiac arrest: initial response and outcome.
AB  - INTRODUCTION: Shockable rhythms are rare in pediatric cardiac arrest and the
      results of defibrillation are uncertain. The objective of this study was to
      analyze the results of cardiopulmonary resuscitation that included defibrillation
      in children. METHODS: Forty-four out of 241 children (18.2%) who were
      resuscitated from inhospital or out-of-hospital cardiac arrest had been treated
      with manual defibrillation. Data were recorded according to the Utstein style.
      Outcome variables were a sustained return of spontaneous circulation (ROSC) and 1
      year survival. Characteristics of patients and of resuscitation were evaluated.
      RESULTS: Cardiac disease was the major cause of arrest in this group. Ventricular
      fibrillation (VF) or pulseless ventricular tachycardia (PVT) was the first
      documented electrocardiogram rhythm in 19 patients (43.2%). A shockable rhythm
      developed during resuscitation in 25 patients (56.8%). The first shock (dose, 2
      J/kg) terminated VF or PVT in eight patients (18.1%). Seventeen children (38.6%)
      needed more than three shocks to solve VF or PVT. ROSC was achieved in 28 cases
      (63.6%) and it was sustained in 19 patients (43.2%). Only three patients (6.8%),
      however, survived at 1-year follow-up. Children with VF or PVT as the first
      documented rhythm had better ROSC, better initial survival and better final
      survival than children with subsequent VF or PVT. Children who survived were
      older than the finally dead patients. No significant differences in response rate
      were observed when first and second shocks were compared. The survival rate was
      higher in patients treated with a second shock dose of 2 J/kg than in those who
      received higher doses. Outcome was not related to the cause or the location of
      arrest. The survival rate was inversely related to the duration of
      cardiopulmonary resuscitation. CONCLUSION: Defibrillation is necessary in 18% of
      children who suffer cardiac arrest. Termination of VF or PVT after the first
      defibrillation dose is achieved in a low percentage of cases. Despite a sustained
      ROSC being obtained in more than one-third of cases, the final survival remains
      low. The outcome is very poor when a shockable rhythm develops during
      resuscitation efforts. New studies are needed to ascertain whether the new
      international guidelines will contribute to improve the outcome of pediatric
      cardiac arrest.

PMID- 16882340
TI  - Optimization of immunomagnetic separation for cord blood-derived hematopoietic
      stem cells.
AB  - BACKGROUND: There is a growing interest in cord blood as a source of primitive
      stem cells with the capacity for multilineage differentiation. Pure cell
      fractions are needed for the characterization and in vitro expansion of stem
      cells as well as for their use in preclinical research. However, enrichment of
      stem cells is challenging due to the lack of stem cell-specific markers and
      gentle protocols for the isolation of highly pure stem cell fractions. Protocols
      developed for the enrichment of peripheral blood-derived stem cells have been
      found to be suboptimal for cord blood. RESULTS: In this study, immunomagnetic
      cell sorting protocols to purify CD34+, CD133+ and Lin- cells from fresh and
      cryopreserved cord blood were optimized. Reproducible purities of up to 97% were
      reached. The selected cells were highly viable having substantial colony-forming
      potential. CONCLUSION: The optimized protocols enable rapid enrichment of highly
      pure hematopoietic stem cells from both fresh and cryopreserved cord blood.

PMID- 16882341
TI  - Rho-kinase regulates tissue morphogenesis via non-muscle myosin and LIM-kinase
      during Drosophila development.
AB  - BACKGROUND: The Rho-kinases (ROCKs) are major effector targets of the activated
      Rho GTPase that have been implicated in many of the Rho-mediated effects on cell
      shape and movement via their ability to affect acto-myosin contractility. The
      role of ROCKs in cell shape change and motility suggests a potentially important
      role for Rho-ROCK signaling in tissue morphogenesis during development. Indeed,
      in Drosophila, a single ROCK ortholog, DRok, has been identified and has been
      found to be required for establishing planar cell polarity. RESULTS: We have
      examined a potential role for DRok in additional aspects of tissue morphogenesis
      using an activated form of the protein in transgenic flies. Our findings
      demonstrate that DRok activity can influence multiple morphogenetic processes,
      including eye and wing development. Furthermore, genetic studies reveal that Drok
      interacts with multiple downstream effectors of the Rho GTPase signaling pathway,
      including non-muscle myosin heavy chain, adducin, and Diaphanous in those
      developmental processes. Finally, in overexpression studies, we determined that
      Drok and Drosophila Lim-kinase interact in the developing nervous system.
      CONCLUSION: These findings indicate widespread diverse roles for DRok in tissue
      morphogenesis during Drosophila development, in which multiple DRok substrates
      appear to be required.

PMID- 16882342
TI  - High-resolution comparative mapping among man, cattle and mouse suggests a role
      for repeat sequences in mammalian genome evolution.
AB  - BACKGROUND: Comparative mapping provides new insights into the evolutionary
      history of genomes. In particular, recent studies in mammals have suggested a
      role for segmental duplication in genome evolution. In some species such as
      Drosophila or maize, transposable elements (TEs) have been shown to be involved
      in chromosomal rearrangements. In this work, we have explored the presence of
      interspersed repeats in regions of chromosomal rearrangements, using an updated
      high-resolution integrated comparative map among cattle, man and mouse. RESULTS:
      The bovine, human and mouse comparative autosomal map has been constructed using
      data from bovine genetic and physical maps and from FISH-mapping studies. We
      confirm most previous results but also reveal some discrepancies. A total of 211
      conserved segments have been identified between cattle and man, of which 33 are
      new segments and 72 correspond to extended, previously known segments. The
      resulting map covers 91% and 90% of the human and bovine genomes, respectively.
      Analysis of breakpoint regions revealed a high density of species-specific
      interspersed repeats in the human and mouse genomes. CONCLUSION: Analysis of the
      breakpoint regions has revealed specific repeat density patterns, suggesting that
      TEs may have played a significant role in chromosome evolution and genome
      plasticity. However, we cannot rule out that repeats and breakpoints accumulate
      independently in the few same regions where modifications are better tolerated.
      Likewise, we cannot ascertain whether increased TE density is the cause or the
      consequence of chromosome rearrangements. Nevertheless, the identification of
      high density repeat clusters combined with a well-documented repeat phylogeny
      should highlight probable breakpoints, and permit their precise dating. Combining
      new statistical models taking the present information into account should help
      reconstruct ancestral karyotypes.

PMID- 16882343
TI  - UVB phototherapy in an outpatient setting or at home: a pragmatic randomised
      single-blind trial designed to settle the discussion. The PLUTO study.
AB  - BACKGROUND: Home ultraviolet B (UVB) treatment is a much-debated treatment,
      especially with regard to effectiveness, safety and side effects. However, it is
      increasingly being prescribed, especially in the Netherlands. Despite ongoing
      discussions, no randomised research has been performed, and only two studies
      actually compare two groups of patients. Thus, firm evidence to support or
      discourage the use of home UVB phototherapy has not yet been obtained. This is
      the goal of the present study, the PLUTO study (Dutch acronym for "national trial
      on home UVB phototherapy for psoriasis"). METHODS: We designed a pragmatic
      randomised single-blind multi-centre trial. This trial is designed to evaluate
      the impact of home UVB treatment versus UVB phototherapy in a hospital outpatient
      clinic as to effectiveness, quality of life and cost-effectiveness. In total 196
      patients with psoriasis who were clinically eligible for UVB phototherapy were
      included. Normally 85% of the patients treated with UVB show a relevant clinical
      response. With a power of 80% and a 0.05 significance level it will be possible
      to detect a reduction in effectiveness of 15%. Effectiveness will be determined
      by calculating differences in the Psoriasis Area and Severity Index (PASI) and
      the Self Administered PASI (SAPASI) scores. Quality of life is measured using
      several validated generic questionnaires and a disease-specific questionnaire.
      Other outcome measures include costs, side effects, dosimetry, concomitant use of
      medication and patient satisfaction. Patients are followed throughout the therapy
      and for 12 months thereafter. The study is no longer recruiting patients, and is
      expected to report in 2006. DISCUSSION: In the field of home UVB phototherapy
      this trial is the first randomised parallel group study. As such, this trial
      addresses the weaknesses encountered in previous studies. The pragmatic design
      ensures that the results can be well generalised to the target population.
      Because, in addition to effectiveness, aspects such as quality of life and cost
      effectiveness are also taken into consideration, this study will produce valuable
      evidence to either support or discourage prescription of home UVB phototherapy.
      TRIAL REGISTRATION: Current controlled trials/Nederlands Trial register:
      ISRCTN83025173. Clinicaltrials.gov: NCT00150930.

PMID- 16882344
TI  - Safety of a 3-weekly schedule of carboplatin plus pegylated liposomal doxorubicin
      as first line chemotherapy in patients with ovarian cancer: preliminary results
      of the MITO-2 randomized trial.
AB  - BACKGROUND: The MITO-2 (Multicentre Italian Trials in Ovarian cancer) study is a
      randomized phase III trial comparing carboplatin plus paclitaxel to carboplatin
      plus pegylated liposomal doxorubicin in first-line chemotherapy of patients with
      ovarian cancer. Due to the paucity of published phase I data on the 3-weekly
      experimental schedule used, an early safety analysis was planned. METHODS:
      Patients with ovarian cancer (stage Ic-IV), aged < 75 years, ECOG performance
      status <or= 2, were randomized to carboplatin AUC 5 plus paclitaxel 175 mg/m2,
      every 3 weeks or to carboplatin AUC 5 plus pegylated liposomal doxorubicin 30
      mg/m2, every 3 weeks. Treatment was planned for 6 cycles. Toxicity was coded
      according to the NCI-CTC version 2.0. RESULTS: The pre-planned safety analysis
      was performed in July 2004. Data from the first 50 patients treated with
      carboplatin plus pegylated liposomal doxorubicin were evaluated. Median age was
      60 years (range 34-75). Forty-three patients (86%) completed 6 cycles. Two thirds
      of the patients had at least one cycle delayed due to toxicity, but 63% of the
      cycles were administered on time. In most cases the reason for chemotherapy delay
      was neutropenia or other hematological toxicity. No delay due to palmar-plantar
      erythrodysesthesia (PPE) was recorded. No toxic death was recorded. Reported
      hematological toxicities were: grade (G) 3 anemia 16%, G3/G4 neutropenia 36% and
      10% respectively, G3/4 thrombocytopenia 22% and 4% respectively. Non
      haematological toxicity was infrequent: pulmonary G1 6%, heart rhythm G1 4%,
      liver toxicity G1 6%, G2 4% and G3 2%. Complete hair loss was reported in 6% of
      patients, and G1 neuropathy in 2%. PPE was recorded in 14% of the cases (G1 10%,
      G2 2%, G3 2%). CONCLUSION: This safety analysis shows that the adopted schedule
      of carboplatin plus pegylated liposomal doxorubicin given every 3 weeks is
      feasible as first line treatment in ovarian cancer patients, although 37% of the
      cycles were delayed due to haematological toxicity. Toxicities that are common
      with standard combination of carboplatin plus paclitaxel (neurotoxicity and hair
      loss) are infrequent with this experimental schedule, and skin toxicity appears
      manageable.

PMID- 16882345
TI  - Prognostic significance of MCM2, Ki-67 and gelsolin in non-small cell lung
      cancer.
AB  - BACKGROUND: Uncontrolled proliferation and increased motility are hallmarks of
      neoplastic cells, therefore markers of proliferation and motility may be valuable
      in assessing tumor progression and prognosis. MCM2 is a member of the
      minichromosome maintenance (MCM) protein family. It plays critical roles in the
      initiation of DNA replication and in replication fork movement, and is intimately
      related to cell proliferation. Ki-67 is a proliferation antigen that is expressed
      during all but G0 phases of the cell cycle. Gelsolin is an actin-binding protein
      that regulates the integrity of the actin cytoskeletal structure and facilitates
      cell motility. In this study, we assessed the prognostic significance of MCM2 and
      Ki-67, two markers of proliferation, and gelsolin, a marker of motility, in non
      small cell lung cancer (NSCLC). METHODS: 128 patients with pathologically
      confirmed, resectable NSCLC (stage I-IIIA) were included. Immunohistochemistry
      was utilized to measure the expressions of these markers in formalin-fixed,
      paraffin-embedded tumor tissues. Staining and scoring of MCM2, Ki-67 and gelsolin
      was independently performed. Analyses were performed to evaluate the prognostic
      significance of single expression of each marker, as well as the prognostic
      significance of composite expressions of MCM2 and gelsolin. Cox regression and
      Kaplan-Meier survival analysis were used for statistical analysis. RESULTS: Of
      the three markers, higher levels of gelsolin were significantly associated with
      an increased risk of death (adjusted RR = 1.89, 95% CI = 1.17-3.05, p = 0.01),
      and higher levels of MCM2 were associated with a non-significant increased risk
      of death (adjusted RR = 1.36, 95% CI = 0.84-2.20, p = 0.22). Combined, adjusted
      analyses revealed a significantly poor prognostic effect for higher expression of
      MCM2 and gelsolin compared to low expression of both biomarkers (RR = 2.32, 95%
      CI = 1.21-4.45, p = 0.01). Ki-67 did not display apparent prognostic effect in
      this study sample. CONCLUSION: The results suggest that higher tumor
      proliferation and motility may be important in the prognosis of NSCLC, and
      composite application of biomarkers might be of greater value than single marker
      application in assessing tumor prognosis.

PMID- 16882346
TI  - Candidate polyanion microbicides inhibit HIV-1 infection and dissemination
      pathways in human cervical explants.
AB  - BACKGROUND: Heterosexual intercourse remains the major route of HIV-1
      transmission worldwide, with almost 5 million new infections occurring each year.
      Women increasingly bear a disproportionate burden of the pandemic, thus there is
      an urgent need to develop new strategies to reduce HIV-1 transmission that could
      be controlled by women themselves. The potential of topical microbicides to
      reduce HIV transmission across mucosal surfaces has been clearly identified, and
      some agents are currently under evaluation in clinical trials. Many of these
      "first generation" microbicides consist of polyanionic compounds designed to
      interfere with viral attachment. Here we have evaluated two candidate polyanion
      compounds in clinical trials, PRO 2000 and dextrin sulphate (DxS) to determine
      their safety and efficacy against in vitro HIV-1 and HSV-2 infection using
      cellular and tissue explant models. RESULTS: PRO 2000 and DxS potently inhibited
      infection by HIV-1 X4 and R5 isolates when present during viral exposure. However
      PRO 2000 required 10-fold and DxS 2000-fold more compound to block infection with
      R5 virus than X4. While both compounds were virucidal for X4 HIV-1, neither was
      virucidal for R5 virus. PRO 2000 efficiently inhibited infection of cervical
      explants and dissemination of virus by migratory DC. DxS was less active, able to
      completely inhibit cervical explant infection, but providing only partial
      reduction of virus dissemination by DC. PRO 2000, but not DxS, also inhibited HIV
      1 binding to DC-SIGN+ cells and trans infection of co-cultured target cells. The
      inflammatory potential of both compounds was screened by measurement of cytokine
      production from cervical explants, and statistically significant increases were
      only observed for IL-1beta and RANTES following treatment with PRO 2000. Both
      compounds also demonstrated potent activity against HSV-2 infection of cervical
      epithelial cells. CONCLUSION: Our results demonstrate that PRO 2000 is a potent
      inhibitor of R5 HIV-1 infection and dissemination pathways in human cervical
      explants. DxS, while demonstrating significant inhibition of R5 infection, was
      less active against DC mediated dissemination pathways. PRO 2000 has now entered
      human phase III efficacy trials.

PMID- 16882347
TI  - Estrogen receptor-alpha and progesterone receptor are expressed in label
      retaining mammary epithelial cells that divide asymmetrically and retain their
      template DNA strands.
AB  - INTRODUCTION: Stem cells of somatic tissues are hypothesized to protect
      themselves from mutation and cancer risk through a process of selective
      segregation of their template DNA strands during asymmetric division. Mouse
      mammary epithelium contains label-retaining epithelial cells that divide
      asymmetrically and retain their template DNA. METHOD: Immunohistochemistry was
      used in murine mammary glands that had been labeled with [3H]thymidine during
      allometric growth to investigate the co-expression of DNA label retention and
      estrogen receptor (ER)-alpha or progesterone receptor (PR). Using the same
      methods, we investigated the co-localization of [3H]thymidine and ER-alpha or PR
      in mammary tissue from mice that had received treatment with estrogen,
      progesterone, and prolactin subsequent to a long chase period to identify label
      retaining cells. RESULTS: Label-retaining epithelial cells (LRECs) comprised
      approximately 2.0% of the entire mammary epithelium. ER-alpha-positive and PR
      positive cells represented about 30-40% of the LREC subpopulation. Administration
      of estrogen, progesterone, and prolactin altered the percentage of LRECs
      expressing ER-alpha. CONCLUSION: The results presented here support the premise
      that there is a subpopulation of LRECs in the murine mammary gland that is
      positive for ER-alpha and/or PR. This suggests that certain mammary LRECs
      (potentially stem cells) remain stably positive for these receptors, raising the
      possibility that LRECs comprise a hierarchy of asymmetrically cycling mammary
      stem/progenitor cells that are distinguished by the presence or absence of
      nuclear steroid receptor expression.

PMID- 16882348
TI  - SOFA is superior to MOD score for the determination of non-neurologic organ
      dysfunction in patients with severe traumatic brain injury: a cohort study.
AB  - OBJECTIVE: To compare the discriminative ability of the SOFA and MOD scoring
      systems with respect to hospital mortality and unfavorable neurologic outcome in
      patients with severe traumatic brain injury admitted to intensive care. METHODS:
      We performed a prospective cohort study at Foothills Medical Centre, the sole
      adult tertiary care trauma center servicing southern Alberta (population
      approximately 1.3 million) All patients >or=16 years of age and older with severe
      traumatic brain injury (sTBI) and intensive care unit length of stay > 48 hours
      between May 1, 2000 and April 31, 2003 were included. Non-neurologic organ
      dysfunction was measured by the SOFA and MODS scoring systems. Comparison of the
      SOFA and MOD score determination of organ dysfunction for each non-neurological
      organ system was examined by calculating the proportion of patients with SOFA and
      MOD component score defined organ failure. Consistent with previous literature,
      organ system failure was defined as a component score >or=3. RESULTS: The odds of
      death and unfavorable neurologic outcome in patients with SOFA defined
      cardiovascular failure were 14.7 times (95% CI: 5.9-36.3) and 7.6 times (95% CI
      3.5-16.3) respectively, that of those without cardiovascular failure. The
      development of SOFA defined cardiovascular failure was a reasonable discriminator
      of hospital mortality and unfavorable neurologic outcome (AuROC=0.75 and 0.73,
      respectively). The odds of death and unfavorable neurologic outcome in patients
      with MOD defined cardiovascular failure were 2.6 times (95% CI: 1.24-5.26) and
      4.1 times (95% CI 1.3-12.4) respectively, that of those without cardiovascular
      failure. The development of MOD defined cardiovascular failure was a poor
      discriminator of hospital mortality and unfavorable neurologic outcome
      (AuROC=0.57 and 0.59 respectively). Both SOFA and MOD defined respiratory failure
      were not statistically associated with hospital mortality. CONCLUSIONS: In
      patients with brain injury, the SOFA scoring system has superior discriminative
      ability and stronger association with outcome compared to the MOD scoring system
      with respect to hospital mortality and unfavorable neurologic outcome.

PMID- 16882349
TI  - Modelling entomological-climatic interactions of Plasmodium falciparum malaria
      transmission in two Colombian endemic-regions: contributions to a National
      Malaria Early Warning System.
AB  - BACKGROUND: Malaria has recently re-emerged as a public health burden in
      Colombia. Although the problem seems to be climate-driven, there remain
      significant gaps of knowledge in the understanding of the complexity of malaria
      transmission, which have motivated attempts to develop a comprehensive model.
      METHODS: The mathematical tool was applied to represent Plasmodium falciparum
      malaria transmission in two endemic-areas. Entomological exogenous variables were
      estimated through field campaigns and laboratory experiments. Availability of
      breeding places was included towards representing fluctuations in vector
      densities. Diverse scenarios, sensitivity analyses and instabilities cases were
      considered during experimentation-validation process. RESULTS: Correlation
      coefficients and mean square errors between observed and modelled incidences
      reached 0.897-0.668 (P > 0.95) and 0.0002-0.0005, respectively. Temperature
      became the most relevant climatic parameter driving the final incidence.
      Accordingly, malaria outbreaks are possible during the favourable epochs
      following the onset of El Nino warm events. Sporogonic and gonotrophic cycles
      showed to be the entomological key-variables controlling the transmission
      potential of mosquitoes' population. Simulation results also showed that
      seasonality of vector density becomes an important factor towards understanding
      disease transmission. CONCLUSION: The model constitutes a promising tool to
      deepen the understanding of the multiple interactions related to malaria
      transmission conducive to outbreaks. In the foreseeable future it could be
      implemented as a tool to diagnose possible dynamical patterns of malaria
      incidence under several scenarios, as well as a decision-making tool for the
      early detection and control of outbreaks. The model will be also able to be
      merged with forecasts of El Nino events to provide a National Malaria Early
      Warning System.

PMID- 16882355
TI  - The role of dopamine in Toxoplasma-induced behavioural alterations in mice: an
      ethological and ethopharmacological study.
AB  - Toxoplasma gondii, a cosmopolitan protozoan parasite, is known to induce
      behavioural alterations in rodents and may exert an effect on human personality
      and behaviour. The mechanism of parasite-induced alterations in host behaviour
      has not been described, but it was hypothesized that development of Toxoplasma
      tissue cysts in the brain could affect the dopaminergic neuromodulatory system.
      In this study, we tested the effect of latent Toxoplasma infection on mouse
      behaviour associated with activity of the dopaminergic system, i.e. locomotion in
      a novel environment and exploration test. Additionally, we examined the
      behavioural response of Toxoplasma-infected mice to a selective dopamine uptake
      inhibitor, GBR 12909. In both genders, Toxoplasma infection decreased locomotion
      in the open field. Infected females displayed an increased level of exploration
      in the holeboard test. GBR 12909 induced suppression in holeboard-exploration in
      the infected males, but had an opposite effect on the controls. These results
      suggest an association between Toxoplasma gondii infection and changes in the
      dopaminergic neuromodulatory system.

PMID- 16882356
TI  - The structure of common DSM-IV and ICD-10 mental disorders in the Australian
      general population.
AB  - BACKGROUND: Patterns of co-occurrence among the common mental disorders may
      provide information about underlying dimensions of psychopathology. The aim of
      the current study was to determine which of four models best fits the pattern of
      co-occurrence between 10 common DSM-IV and 11 common ICD-10 mental disorders.
      METHOD: Data were from the Australian National Survey of Mental Health and Well
      Being (NSMHWB), a large-scale community epidemiological survey of mental
      disorders. Participants consisted of a random population-based sample of 10641
      community volunteers, representing a response rate of 78%. DSM-IV and ICD-10
      mental disorder diagnoses were obtained using the Composite International
      Diagnostic Interview (CIDI), version 2.0. Confirmatory factor analysis (CFA) was
      used to assess the relative fit of competing models. RESULTS: A hierarchical
      three-factor variation of a two-factor model demonstrated the best fit to the
      correlations among the mental disorders. This model included a distress factor
      with high loadings on major depression, dysthymia, generalized anxiety disorder
      (GAD), post-traumatic stress disorder (PTSD) and neurasthenia (ICD-10 only); a
      fear factor with high loadings on social phobia, panic disorder, agoraphobia and
      obsessive-compulsive disorder (OCD); and an externalizing factor with high
      loadings on alcohol and drug dependence. The distress and fear factors were best
      conceptualized as subfactors of a higher order internalizing factor. CONCLUSIONS:
      A greater focus on underlying dimensions of distress, fear and externalization is
      warranted.

PMID- 16882357
TI  - Reaction time, inhibition, working memory and 'delay aversion' performance:
      genetic influences and their interpretation.
AB  - BACKGROUND: For candidate endophenotypes to be useful for psychiatric genetic
      research, they first of all need to show significant genetic influences. To
      address the relative lack of previous data, we set to investigate the extent of
      genetic and environmental influences on performance in a set of theoretically
      driven cognitive-experimental tasks in a large twin sample. We further aimed to
      illustrate how test-retest reliability of the measures affects the estimates.
      METHOD: Four-hundred 7- to 9-year-old twin pairs were assessed individually on
      tasks measuring reaction time, inhibition, working memory and 'delay aversion'
      performance. Test-retest reliability data on some of the key measures were
      available from a previous study. RESULTS: Several key measures of reaction time,
      inhibition and working-memory performance indicated a moderate degree of genetic
      influence. Combining data across theoretically related tasks increased the
      heritability estimates, as illustrated by the heritability estimates of 60% for
      mean reaction time and 50% for reaction-time variability. Psychometric properties
      (reliability or ceiling effects) had a substantial influence on the estimates for
      some measures. CONCLUSIONS: The data support the usefulness of several of the
      variables for endophenotype studies that aim to link genes to cognitive and
      motivational processes. Importantly, the data also illustrate specific conditions
      under which the true extent of genetic influences may be underestimated and hence
      the usefulness for genetic mapping studies compromised, and suggest ways to
      address this.

PMID- 16882359
TI  - Evaluation of epidermal growth factor receptor gene and chromosome 7 alterations
      in squamous cell carcinoma of the larynx, using chromogenic in situ hybridization
      on tissue microarrays.
AB  - AIMS: To identify subgroups of patients with squamous cell carcinoma (SCC) of the
      larynx, characterized by the specific deregulation mechanism of the epidermal
      growth factor receptor (EGFR) gene, and to evaluate EGFR protein expression
      levels and correlate these with biological and clinicopathological parameters.
      MATERIALS AND METHODS: Using tissue microarray technology, 50 formalin-fixed,
      paraffin-embedded primary laryngeal SCCs were cored and re-embedded into one
      block. Immunohistochemistry and chromogenic in situ hybridization were performed.
      RESULTS: Epidermal growth factor receptor protein over-expression was observed in
      27/50 (54 per cent) cases and was statistically associated with tumour grade
      (p=0.028). Epidermal growth factor receptor gene alterations were identified in
      5/50 (10 per cent) cases, which demonstrated amplification (n=4) and deletion
      (n=1). Chromosome 7 instability was detected in 8/50 (16 per cent) cases.
      CONCLUSIONS: Epidermal growth factor receptor over-expression is a frequent event
      in SCCs, but it does not predict a specific molecular mechanism of gene
      deregulation for targeted therapeutic strategies via monoclonal antibodies.

PMID- 16882358
TI  - Calpain- and caspase-mediated alphaII-spectrin and tau proteolysis in rat
      cerebrocortical neuronal cultures after ecstasy or methamphetamine exposure.
AB  - Abuse of 3,4-methylenedioxymethamphetamine (MDMA or Ecstasy) and methamphetamine
      (Meth or Speed) is a growing international problem with an estimated 250 million
      users of psychoactive drugs worldwide. It is important to demonstrate and
      understand the mechanism of neurotoxicity so potential prevention and treatment
      therapies can be designed. In this study rat primary cerebrocortical neuron
      cultures were challenged with MDMA and Meth (1 or 2 mM) for 24 and 48 h and
      compared to the excitotoxin N-methyl-D-aspartate (NMDA). The neurotoxicity of
      these drugs, as assessed by microscopy, lactate dehydrogenase release and
      immunoblot, was shown to be both dose- and time-dependent. Immunoblot analysis
      using biomarkers of cell death showed significant proteolysis of both alphaII
      spectrin and tau proteins. Breakdown products of alphaII-spectrin (SBDPs) of 150,
      145, and 120 kDa and tau breakdown products (TBDPs) of 45, 32, 26, and 14 kDa
      were observed. The use of the protease inhibitors calpain inhibitor SJA6017 and
      caspase inhibitors z-VAD-fmk and Z-D-DCB, attenuated drug-induced alphaII
      spectrin and tau proteolysis. The calpain inhibitor reduced the calpain-induced
      breakdown products SBDP145 and TBDP14, but there was an offset increase in the
      caspase-mediated breakdown products SBDP120 and TBDP45. The caspase inhibitors,
      on the other hand, decreased SBDP120 and TBDP45. These data suggest that both
      MDMA and Meth trigger concerted proteolytic attacks of the structural proteins by
      both calpain and caspase family of proteases. The ability of the protease
      inhibitors to reduce the damage caused by these drugs suggests that the treatment
      arsenal could include similar drugs as possible tools to combat the drug-induced
      neurotoxicity in vivo.

PMID- 16882361
TI  - Locating the scala media in the fixed human temporal bone for therapeutic access:
      a preliminary study.
AB  - OBJECTIVE: To investigate the location of the scala media in relation to the
      round window niche in human temporal bones. DESIGN: Ten human temporal bones were
      investigated by radical mastoidectomy and promontory drill-out. SETTING: Temporal
      bone laboratory. OUTCOME MEASURES: The distance from the scala media to the
      anterior edge of the round window niche, measured by Fisch's stapedectomy
      measuring cylinders. RESULTS: The scala media was identified at the transection
      point of a vertical line 1.6 to 2.2 mm (mean=1.8 mm; standard deviation=0.2)
      anterior to the anterior edge of the round window niche and a horizontal line 0.2
      mm inferior to the lower border of the oval window. CONCLUSION: This report
      demonstrates the point of entry into the scala media via the promontory in fixed
      temporal bone models, which may provide a site of entry for stem cells and gene
      therapy insertion.

PMID- 16882360
TI  - Thyroid pathology and the globus symptom: are they related? A two year
      prospective trial.
AB  - INTRODUCTION: The globus sensation is a constant feeling of a lump in the throat
      and may be associated with thyroid enlargement. A two year prospective study was
      set up to ascertain the relationship between thyroid pathology and globus
      symptoms. MATERIALS AND METHODS: All patients undergoing thyroid surgery over a
      two year period were included. Patients were questioned pre- and post
      operatively. Globus symptom scores were recorded using a visual analogue scale.
      The size, weight and histological features of the removed specimens were
      correlated and statistical analysis performed. RESULTS: Two hundred patients were
      included in the study; 58 were symptomatic for globus pharyngeus pre-operatively,
      and 80 per cent of these patients' symptoms resolved post-operatively (p < or =
      0.0001). Patients with histological features of inflammation showed the greatest
      improvement (p < or = 0.0001). CONCLUSION: As many as one-third of patients with
      a thyroid mass will complain of a globus-like symptom. Patients undergoing
      thyroid surgery, who are symptomatic for globus pharyngeus, can expect that their
      symptoms will improve following surgery.

PMID- 16882363
TI  - Bone morphogenetic proteins in orthopaedic trauma: recent clinical findings with
      human bone morphogenetic protein-2 (rhBMP-2).
AB  - This article introduces papers based on presentations from a symposium entitled
      "Bone Morphogenic Protein Advisory Meeting in Orthopaedic Trauma", where recent
      clinical findings with human bone morphogenetic protein-2 (rhBMP-2) were
      reviewed. It also presents two case studies which illustrate the clinical
      problems with the potential morbidity of tibial fractures and the potential
      benefits of the use of rhBMP-2 at surgery. The article concludes with a summary
      of the symposium. Tibial shaft fracture repair is associated with a significant
      financial burden on the patient, the health care providers and the medical
      insurance companies. It is anticipated that the clinical advantages of rhBMP-2
      could lead to cost savings both inside and outside the hospital setting.

PMID- 16882362
TI  - Rosen mobilization of the stapes: does it have a place in modern otology?
AB  - We describe two patients with stapes fixation, in both of whom Rosen mobilization
      seemed to be the most prudent surgical choice. In both cases, a useful hearing
      gain was achieved initially. In the patient with otosclerosis, the conductive
      hearing loss recurred and a stapedectomy was subsequently carried out. In the
      patient with congenital stapes fixation, the hearing gain was maintained for two
      years eight months. We believe that this technique still has a place in stapes
      surgery in rare instances.

PMID- 16882364
TI  - Bone morphogenetic protein signal transduction in bone.
AB  - Bone morphogenetic proteins (BMPs) promote bone formation by stimulating the
      proliferation and differentiation of osteoblasts. It has been suggested that non
      union of the bone, and delayed healing, may be the result of decreased levels of
      BMP activity. Activation of BMP receptors initiates phosphorylation of the
      downstream effector proteins, known as receptor-regulated Smads, leading to
      signal transduction. Receptor-regulated Smads form a hetero-oligomeric complex
      with a common mediator Smad, which translocates into the nucleus and regulates
      target gene transcription. The BMP signalling cascade is closely regulated, with
      the inhibitory Smads blocking the intracellular signal cascade. Extracellular
      antagonists, such as noggin, inhibit binding to BMP receptors. BMP-2 and BMP-7
      have demonstrated clinical utility for bone regeneration, and are commercially
      available through the use of recombinant DNA technology.

PMID- 16882365
TI  - Recent developments in the use of bone morphogenetic protein in orthopaedic
      trauma surgery.
AB  - Delayed healing and non-union remain common problems in the treatment of open
      tibial shaft fractures. Additional surgical treatments may be required to
      facilitate healing. The efficacy of recombinant human bone morphogenetic protein
      2 (rhBMP-2), as an adjunct to the standard of care, has been investigated in the
      BMP-2 Evaluation in Surgery for Tibial Trauma (BESTT) study. This prospective,
      randomised, multicentre, controlled study included 450 patients with acute,
      diaphyseal, open tibial fractures. A significant reduction in the risk of
      secondary intervention was observed in the 1.50 mg/mL rhBMP-2 group compared with
      the standard of care alone group (p = 0.0005). In a subgroup analysis of 131
      patients with Gustilo-Anderson grade IIIA or IIIB open tibial fractures, using
      data combined from the BESTT study and a study conducted at 10 level I US trauma
      centres, a significant reduction in the incidence of secondary autologous bone
      graft procedures was observed with 1.50 mg/mL rhBMP-2 compared with the standard
      of care (p = 0.0005). The influence of fracture gap on the re-operation rate has
      also been examined in the BESTT study. In the 1.50 mg/mL rhBMP-2 group, patients
      with a 0 mm fracture gap had significantly less re-operations compared with those
      patients with a greater than 2 mm gap (p = 0.048).

PMID- 16882366
TI  - Economic considerations for the use of recombinant human bone morphogenetic
      protein-2 in open tibial fractures in Europe: the German model.
AB  - The addition of recombinant human bone morphogenetic protein (rhBMP-2) to the
      standard of care, consisting of soft tissue management and intramedullary
      nailing, in the BMP-2 Evaluation in Surgery for Tibial Trauma (BESTT) study led
      to a significantly better outcome for the patient. Reductions in fracture healing
      time, secondary interventions for delayed fracture healing and infection rates
      were observed with 1.50 mg/mL rhBMP-2 compared with the standard of care alone.
      In Germany the approximate cost of applying one dose of recombinant human bone
      morphogenetic protein-2 (rhBMP-2) to an open tibial fracture is euro2970. The
      current German-Diagnosis-Related Group reimbursement system provides one flat
      rate per hospital stay or treatment case, and does not take into account the
      costs of rhBMP-2 application. Therefore there is no reimbursement for the price
      of rhBMP-2 for hospitals by health insurance companies. However, the above
      mentioned improvements in medical outcome could lead to important savings for
      health care systems, particularly for health insurance companies. A sound
      economic model to assess the cost-effectiveness and budget impact of rhBMP-2 is
      required. Using medical data from the BESTT study the differences in fracture
      healing time, in reduction of secondary interventions for fracture healing and
      infection treatment can be transferred into economic savings. It is anticipated
      that the overall savings that can be achieved by rhBMP-2 treatment in open tibia
      fractures, offset the upfront price of rhBMP-2 and lead to net savings for health
      insurance companies.

PMID- 16882370
TI  - Imaging in primary care.

PMID- 16882371
TI  - Privatising primary care.

PMID- 16882372
TI  - Poor access to care: rural health deprivation?

PMID- 16882373
TI  - Negative chest X-rays in primary care patients with lung cancer.
AB  - BACKGROUND: The main investigation for suspected lung cancer in primary care is a
      chest X-ray. Reports from secondary care show that some patients with normal
      chest X-rays transpire to have lung cancer. The assumption is that this occurs
      rarely in primary care. AIM: The aim of this study was to examine the frequency
      of misleading chest X-rays in primary care, and whether there were any particular
      symptoms associated with them. DESIGN OF STUDY: Retrospective cohort study of the
      primary care records of 247 lung cancer patients diagnosed between 1998-2002.
      SETTING: All general practices in Exeter Primary Care Trust, Devon, UK. METHOD:
      All chest X-rays and all common symptoms of lung cancer reported to primary care
      were identified from the medical records. X-ray results were categorised into
      three groups by the radiologist's report: normal; abnormal but no malignancy
      suspected (together classified as negative X-rays); or abnormal with possible
      malignancy. RESULTS: Of the 247 patients, 164 (66%) had a chest X-ray taken in
      primary care during the year before diagnosis: 126 of these (77%) were abnormal
      with possible malignancy; 21 (13%) were abnormal but with no malignancy
      suspected; in 17 (10%) the X-ray was reported as normal. Thus, 38 of 164 patients
      (23%; 95% confidence interval = 16 to 32%) had a negative X-ray. Negative X-rays
      were less common in the 90 days before diagnosis. No particular symptoms were
      significantly associated with negative X-rays. CONCLUSION: Nearly a quarter of
      chest X-rays requested from primary care in lung cancer patients are negative.
      Further investigation is warranted with continuing or changing symptoms, even if
      the X-ray is not suggestive of malignancy.

PMID- 16882374
TI  - Chest radiography in general practice: indications, diagnostic yield and
      consequences for patient management.
AB  - BACKGROUND: Chest radiography (CXR) is frequently performed in Western societies.
      There is insufficient knowledge of its diagnostic value in terms of changes in
      patient management decisions in primary care. AIM: To assess the influence of CXR
      on patient management in general practice. DESIGN OF STUDY: Prospective cohort
      study. SETTING: Seventy-eight GPs and three general hospitals in the Netherlands.
      METHOD: Patients (n = 792) aged > or =18 years referred by their GPs for CXR were
      included. The main outcome was change in patient management assessed by means of
      questionnaires filled in by GPs before and after CXR. RESULTS: Mean age of the
      patients was 57.3+/-16.2 years and 53% were male. Clinically relevant
      abnormalities were found in 24% of the CXRs. Patient management changed in 60% of
      the patients following CXR. Main changes included: fewer referrals to a medical
      specialist (from 26 to 12%); reduction in initiation or change in therapy (from
      24 to 15%); and more frequent reassurance (from 25 to 46%). However, this
      reassurance was not perceived as such in a quarter of these patients. A change in
      patient management occurred significantly more frequently in patients with
      complaints of cough (67%), those who exhibited abnormalities during physical
      examination (69%), or those with a suspected diagnosis of pneumonia (68%).
      CONCLUSION: Patient management by the GP changed in 60% of patients following
      CXR. CXR substantially reduced the number of referrals and initiation or change
      in therapy, and more patients were reassured by their GP. Thus, CXR is an
      important diagnostic tool for GPs and seems a cost-effective diagnostic test.

PMID- 16882375
TI  - Effective improvement of doctor-patient communication: a randomised controlled
      trial.
AB  - BACKGROUND: Doctor-patient communication is an essential component of general
      practice. Improvement of GPs' communication patterns is an important target of
      training programmes. Available studies have so far failed to provide conclusive
      evidence of the effectiveness of educational interventions to improve doctor
      patient communication. AIM: To examine the effectiveness of a learner-centred
      approach that focuses on actual needs, to improve GPs' communication with
      patients. DESIGN OF STUDY: Randomised controlled trial. SETTING: One hundred
      volunteer GPs in the Netherlands. METHOD: The intervention identified individual
      GPs' deficiencies in communication skills by observing authentic consultations in
      their own surgery. This performance assessment was followed by structured
      activities in small group meetings, aimed at remedying the identified
      shortcomings. Outcomes were measured using videotaped consultations in the GPs'
      own surgery before and after the intervention. Communication skills were rated
      using the MAAS-Global, a validated checklist. RESULTS: The scores in the
      intervention group demonstrated a significant improvement compared with those of
      the control group (95% confidence interval = 0.04 to 0.75). The effect size was
      moderate to large (d-value = 0.66). The level of participation significantly
      contributed to the effectiveness. Largest improvement was found on patient
      centred communication skills. CONCLUSION: The approach of structured individual
      improvement activities based on performance assessment is more effective in
      improving communication skills than current educational activities.

PMID- 16882376
TI  - Psychosocial impact of Chlamydia trachomatis testing in general practice.
AB  - BACKGROUND: Urogenital Chlamydia trachomatis infections are widespread, and each
      year many tests are performed in general practice. AIM: First, to quantify the
      magnitude of stigmatization, problems related to partner, and anxiety of
      infertility among men and women tested for C. trachomatis in general practice.
      Second, to investigate the effect of a C. trachomatis test result on planned
      future condom use. DESIGN OF STUDY: Comparative cross-sectional study. SETTING:
      General practices in Aarhus County, Denmark. METHOD: Men and women tested for C.
      trachomatis in general practice were given a questionnaire about feelings of
      stigmatization, fear of partner's reaction, fear of future infertility and other
      psychosocial side effects related to being infected or not infected with C.
      trachomatis. RESULTS: A total of 277 participated in the study. The response
      rates were 61% (82/135) and 54% (195/365) among infected and non-infected
      individuals, respectively. Among the infected individuals 32% (9/28) of the men's
      partners and 35% (19/54) of the women's partners were upset about the test
      result, 9% (5/54) of the women and 11% (3/28) of the men split with their
      partner, 59% (32/54) of the women and 54% (15/28) of the men expressed
      nervousness about infertility, and 91% (19/21) of the women but only 56% (5/9) of
      the men said that they would use a condom more often in the future. All these
      figures were significantly lower for both men and women having C. trachomatis
      negative test results. CONCLUSION: A chlamydia test affects the individual in
      terms of sexuality, relation to partner, reproduction, and future contraceptive
      strategy. The influence is highest among women and individuals with a positive
      test result. These findings should be taken into account in screening programmes
      targeting young women and men.

PMID- 16882377
TI  - Factors that influence the detection of psychological problems in adolescents
      attending general practices.
AB  - BACKGROUND: Epidemiological studies indicate that the prevalence of psychological
      problems in patients attending primary care services may be as high as 25%. AIM:
      To identify factors that influence the detection of psychological difficulties in
      adolescent patients receiving primary care in the UK. DESIGN OF STUDY: A
      prospective study of 13-16 year olds consecutively attending general practices.
      SETTING: General practices, Norfolk, UK. METHOD: Information was obtained from
      adolescents and parents using the validated Strengths and Difficulties
      Questionnaire (SDQ) and from GPs using the consultation assessment form. RESULTS:
      Ninety-eight adolescents were recruited by 13 GPs in Norfolk (mean age = 14.4
      years, SD = 1.08; 38 males, 60 females). The study identified psychological
      difficulties in almost one-third of adolescents (31/98, 31.6%). Three factors
      significant to the detection of psychological disorders in adolescents were
      identified: adolescents' perceptions of difficulties according to the self-report
      SDQ, the severity of their problems as indicated by the self-report SDQ, and
      whether psychological issues were discussed in the consultation. GPs did not
      always explore psychological problems with adolescents, even if GPs perceived
      these to be present. Nineteen of 31 adolescents with psychological difficulties
      were identified by GPs (sensitivity = 61.2%, specificity = 85.1%). A management
      plan or follow-up was made for only seven of 19 adolescents identified,
      suggesting that ongoing psychological difficulties in many patients are not being
      addressed. CONCLUSIONS: GPs are in a good position to identify psychological
      issues in adolescents, but GPs and adolescents seem reluctant to explore these
      openly. Open discussion of psychological issues in GP consultations was found to
      be the most important factor in determining whether psychological difficulties in
      adolescents are detected by GPs.

PMID- 16882378
TI  - The use of cardiovascular risk factor information in practice databases: making
      the best of patient data.
AB  - BACKGROUND: Primary care teams record cardiovascular risk factor data on their
      patients to help them identify and treat patients eligible for prevention.
      However, it is not known to what extent this information is already available to
      clinicians, or the extent to which it is used. AIM: To assess the extent to which
      risk factor is recorded, and to determine the cost-effectiveness of using
      recorded risk factor information in order to identify and treat eligible
      patients. DESIGN OF STUDY: An Excel-based model of the incremental costs and
      benefits of assessment and treatment. SETTING: Two general practices in the West
      Midlands. METHOD: Untreated, non-diabetic patients, aged 35-74 years, were
      identified from each practice, and risk factor data was uploaded into an Excel
      spreadsheet. The completeness of risk factor data was assessed. The costs and
      benefits of assessing and treating patients, in descending order of estimated
      cardiovascular risk, were then modelled. RESULTS: In each practice, 72.9% and
      77.7% of patients had a record of their blood pressure, 26.9% and 25.7% were
      eligible for at least one treatment: aspirin was the most common treatment
      followed by antihypertensives. With patients systematically assessed in
      descending order of cardiovascular risk, 78% of eligible patients and 87% of
      preventable cardiovascular events are found in the first two deciles of the
      target population. CONCLUSIONS: Lack of risk factor information is not the
      principal constraint on cardiovascular prevention. Practices have sufficient risk
      factor data to inform an efficient, targeted prevention strategy.

PMID- 16882379
TI  - Developing clinical rules to predict urinary tract infection in primary care
      settings: sensitivity and specificity of near patient tests (dipsticks) and
      clinical scores.
AB  - BACKGROUND: Suspected urinary tract infection (UTI) is one of the most common
      presentations in primary care. Systematic reviews have not documented any
      adequately powered studies in primary care that assess independent predictors of
      laboratory diagnosis. AIM: To estimate independent clinical and dipstick
      predictors of infection and to develop clinical decision rules. DESIGN OF STUDY:
      Validation study of clinical and dipstick findings compared with laboratory
      testing. SETTING: General practices in the south of England. METHOD: Laboratory
      diagnosis of 427 women with suspected UTI was assessed using European urinalysis
      guidelines. Independent clinical and dipstick predictors of diagnosis were
      estimated. RESULTS: UTI was confirmed in 62.5% of women with suspected UTI. Only
      nitrite, leucocyte esterase (+ or greater), and blood (haemolysed trace or
      greater) independently predicted diagnosis (adjusted odds ratios 6.36, 4.52, 2.23
      respectively). A dipstick decision rule, based on having nitrite, or both
      leucocytes and blood, was moderately sensitive (77%) and specific (70%); positive
      predictive value (PPV) was 81% and negative predictive value (NPV) was 65%.
      Predictive values were improved by varying the cut-off point: NPV was 73% for all
      three dipstick results being negative, and PPV was 92% for having nitrite and
      either blood or leucocyte esterase. A clinical decision rule, based on having two
      of the following: urine cloudiness, offensive smell, and dysuria and/or nocturia
      of moderate severity, was less sensitive (65%) (specificity 69%; PPV 77%, NPV
      54%). NPV was 71% for none of the four clinical features, and the PPV was 84% for
      three or more features. CONCLUSIONS: Simple decision rules could improve
      targeting of investigation and treatment. Strategies to use such rules need to
      take into account limited negative predictive value, which is lower than expected
      from previous research.

PMID- 16882380
TI  - The relationship between prescribing expenditure and quality in primary care: an
      observational study.
AB  - BACKGROUND: If all GPs target their prescribing appropriately, then a positive
      relationship may be expected between targeting quality indicators and associated
      prescribing expenditure. Little is known about this relationship. AIM: To explore
      the relationship between prescribing quality indicators and associated
      prescribing expenditures. DESIGN: Observational study of prescribing expenditure
      and quality indicators. SETTING: Seventy-one of the 121 practices in the Norfolk
      and Waveney area of East Anglia in England. METHOD: Data were collected on
      quality indicators for 2002-2003 in seven areas likely to produce the greatest
      number of lives saved over a period of 1 year. This was linked to routine data on
      associated pharmaceutical expenditure. RESULTS: There was considerable variation
      in quality in all areas apart from influenza immunisation. Significant
      correlations between prescribing quality and expenditure were found in only two
      of the seven areas. When quality scores were combined into a composite quality
      index weighted by health gain, a small positive association was found, but this
      association is lost if all indicators are weighted equally. CONCLUSIONS: There
      appeared to be no relationship between quality indicators and prescribing
      expenditure at the practice level for most of the therapeutic areas studied. This
      suggests the possibility that there may be scope for some GPs to target
      prescribing more appropriately towards high risk patients -- and thus save more
      lives -- without increasing prescribing expenditure.

PMID- 16882381
TI  - General practice characteristics associated with rates of testing and detection
      of hepatitis C: cross-sectional study in Nottingham and Derbyshire.
AB  - The aim of this study was to determine general practice characteristics
      associated with testing rates for hepatitis C virus (HCV) and the proportion of
      tests with a positive result. The study included all patients tested for HCV from
      all general practices in the primary care trusts in Nottingham and Southern
      Derbyshire, UK over 2 years. There was a large variation between practices in HCV
      testing rates and the proportion of positive tests. Single-handed practices had
      higher testing rates and rates of positive results. Practices where at least half
      of the GPs were female had higher testing rates but lower positivity rates. The
      variation observed was not explained by deprivation or rurality of the practice.

PMID- 16882382
TI  - Changing pattern of referral to a diabetes clinic following implementation of the
      new UK GP contract.
AB  - BACKGROUND: The aim of this study was to determine the impact of the new GMS
      contract on referral patterns to a secondary care diabetes clinic. All new
      patient referrals received from primary care to a hospital diabetes service were
      surveyed. No significant change in referrals was seen 6 months after
      implementation of the GMS contract. There was, however, an increase in referrals
      for poor glycaemic control after implementation of the new GMS contract, and the
      glycaemic threshold for referral with poor glycaemic control has reduced (9.7%
      versus 10.6%, P = 0.006, mean difference = 0.9% [95% confidence interval = 0.4 to
      1.3%]).

PMID- 16882383
TI  - Improving consultations in general practice for non English-speaking patients.

PMID- 16882384
TI  - Under pressure.

PMID- 16882385
TI  - Sex inequalities.

PMID- 16882386
TI  - Written on the body.

PMID- 16882387
TI  - Ensuring confidentiality.

PMID- 16882389
TI  - Using patient records for medical research.

PMID- 16882392
TI  - Regime change.

PMID- 16882391
TI  - Nurse-led general practice: the changing face of general practice?

PMID- 16882394
TI  - Deprivation and primary care: a time to revisit.

PMID- 16882398
TI  - Causes and treatment of vitreous hemorrhage.
AB  - Vitreous hemorrhage is common, with varied clinical manifestations and causes.
      The most common causes include proliferative diabetic retinopathy, vitreous
      detachment with or without retinal breaks, and trauma. Less common causes include
      vascular occlusive disease, retinal arterial macroaneurysm, hemoglobinopathies,
      age-related macular degeneration, intraocular tumors, and others. The natural
      history depends on the underlying cause, and is generally more favorable in eyes
      without underlying disease. Treatment is directed at the underlying cause, such
      as laser photo-coagulation for proliferative diabetic retinopathy or for retinal
      breaks. Occasionally, hemorrhage does not resolve spontaneously and vitrectomy
      surgery is necessary and beneficial. New strategies for the treatment of vitreous
      hemorrhage, such as pharmacologic vitreous liquefaction, may be important in the
      future.

PMID- 16882399
TI  - Avoiding and managing the dislocated crystalline lens.
AB  - A major complication of cataract surgery is the posterior dislocation of
      crystalline lens material, which may lead to poor visual outcomes. Knowledge of
      preoperative high-risk situations, causes of lens dislocation, and intraoperative
      warning signs should lead to reduced complications. This update reviews
      techniques to avoid the dislocated lens, and management options if this
      complication does occur.

PMID- 16882400
TI  - Comments on: Avoiding and managing the dislocated crystalline lens.

PMID- 16882401
TI  - Current concepts in the pathogenesis and management of exfoliation syndrome and
      exfoliative glaucoma.
AB  - Exfoliative glaucoma is a common, sight-threatening disease that develops as a
      consequence of exfoliation syndrome. There are important differences in the
      clinical appearance, course, and prognosis of exfoliative glaucoma versus primary
      open-angle glaucoma. At the clinical, biochemical, and cellular levels,
      exfoliative glaucoma is a distinct entity, with an intriguing mechanism of
      development and numerous systemic manifestations that require further
      elucidation. The subtlety of clinical signs results in the diagnosis of
      exfoliative glaucoma often being overlooked and resulting in less-than-ideal
      management. We provide an overview of recent studies investigating the medical,
      laser, and surgical therapy of exfoliative glaucoma, with a focus on innovative
      approaches that may slow the progression of, or even prevent, the development of
      exfoliation syndrome and exfoliative glaucoma.

PMID- 16882402
TI  - Comments on: Current concepts in the pathogenesis and management of exfoliation
      syndrome and exfoliative glaucoma.

PMID- 16882403
TI  - Emmetropization in accommodative esotropia: an update and review.
AB  - Many children with accommodative esotropia are able to successfully discontinue
      spectacle wear, while others require spectacle correction into adulthood. Parents
      often ask about the likelihood of glasses being required on a long-term basis and
      whether use of spectacles will cause dependency. Most infants are hyperopic and
      gradually become emmetropic. The extent to which accommodation and spectacle use
      affect this process is still debated. However, certain characteristics, such as
      degree of hyperopia, can help predict long-term spectacle requirement.

PMID- 16882404
TI  - Comments on: Emmetropization in accommodative esotropia: an update and review.

PMID- 16882406
TI  - Recurrent subconjunctival hemorrhage.

PMID- 16882407
TI  - The development of a laparoscopic donor nephrectomy program in a de novo renal
      transplant program: Evolution of technique and results in over 200 cases.
AB  - BACKGROUND AND OBJECTIVES: In 1999, our institution began a kidney transplant
      program with collaboration between the departments of General
      Surgery/Transplantation and Urology. From the onset, donor nephrectomies were
      performed laparoscopically and are currently the domain of Urology, which had no
      prior laparoscopic experience before this undertaking. We reviewed our
      experience. METHODS: A database of our experience was kept prospectively from
      June 1999 to November 2004. Records of both donors and recipients were reviewed.
      Special attention was directed toward our changes in technique and their
      relationship to outcomes, with emphasis on graft extraction and overall
      complication rates. RESULTS: We reviewed the records of 205 consecutive
      procedures. We report excellent donor outcomes, including mean operative time
      (112 minutes), estimated blood loss (120 mL), and length of stay (2.3 days).
      Complication (14.1%) and open conversion (1.5%) rates were low. For the
      recipients, early (98.0%) and 1-year (94.7%) graft survival, and ureteral
      ischemia (2.4%) rates were also appropriate with contemporary experience.
      CONCLUSIONS: We report our results on laparoscopic donor nephrectomy in a de novo
      renal transplant program. Because of this experience, we have ventured into other
      horizons of urologic laparoscopy and currently produce enough volume to support a
      laparoscopic fellowship. We feel that a productive donor nephrectomy program can
      enhance urologic laparoscopic programs and should be taken advantage of when
      available.

PMID- 16882409
TI  - Comparative analysis of early perioperative outcomes following radical cystectomy
      by either the robotic or open method.
AB  - OBJECTIVE: We analyzed early perioperative outcomes following radical cystectomy
      by the robotic method compared with the conventional open method. METHODS: All
      relevant clinical information was entered in a Microsoft Access Database and
      queried. P < 0.05 were considered statistically significant. RESULTS: The study
      cohort comprised 37 consecutive patients undergoing radical cystectomy; 24
      (64.9%) cases were performed by the conventional open method and 13 (29.7%) by
      the robotic method. Body mass index, age, sex, blood transfusion rate, and median
      decrease in hemoglobin were comparable between the 2 groups. The robotic method
      resulted in significantly lower median estimated blood loss, shorter hospital
      stay, and longer operating time compared with the open group (P < 0.05). Four
      (16.7%) perioperative complications occurred in the open group compared with 2
      (15.4%) in the robotic group (P = 1.0). The incidence of organ-confined (< or
      =T2N0Mx) disease was 9 (37.5%) and 7 (53.8%) in the open and robotic groups,
      respectively (P = 0.49). CONCLUSIONS: Radical cystectomy by the robotic method
      produces early perioperative results comparable to those of the open method.
      Although intraoperative estimated blood loss and hospital stay were significantly
      lower in the robotic group, operative time was longer which likely reflects our
      early operative experience with radical cystectomy by the robotic method.

PMID- 16882408
TI  - Laparoscopic vascular control techniques in donor nephrectomy: Effects on vessel
      length.
AB  - BACKGROUND: Various techniques for vascular control have been used during
      urologic laparoscopic procedures. The importance of optimizing the vessel length
      and securing reliable vascular control are critical for procedures like
      laparoscopic donor nephrectomy. We aimed to determine the length of vessel lost
      by using 4 common techniques of vascular control in a fresh human cadaveric
      vascular model. METHODS: The techniques include application of 2 non-absorbable
      polymer-ligating clips (10-mm Hem-o-Lok MLX Weck Closure Systems, Research
      Triangle Park, NC), Endo-GIA II stapler (30-mm length, 2.5-mm staples, Auto
      Suture, US Surgical, Norwalk, CT), Endopath ETS35 stapler (35 mm length, 2.5mm
      staples, Ethicon Endo-Surgery), and the Endo Ta-30 stapler (30-mm length, 2.5-mm
      staples, Auto Suture, US Surgical, Norwalk, CT). RESULTS: The Endo-TA-30 stapler
      and the polymer clips resulted in significantly less compromise of the vessel
      length, when compared with the other methods of vascular control. CONCLUSIONS:
      The Endo-TA-30 stapler and the polymer clips can be applied during laparoscopic
      procedures where optimizing vascular length is important.

PMID- 16882410
TI  - Two trocar laparoscopic varicocelectomy: approach and outcomes.
AB  - BACKGROUND AND OBJECTIVES: The surgical indications and proper management of
      varicoceles in the pediatric population continue to be controversial.
      Historically, open surgical approaches have had recurrence rates between 2% to 6%
      and a low rate of complications. We present a modified laparoscopic technique for
      the treatment of clinically significant varicoceles. METHODS: Consecutive
      pediatric patients presenting with clinically significant varicoceles between May
      2000 and July 2003 were considered for laparoscopic varicocelectomy. A 5-mm 2
      port laparoscopic varicocelectomy was performed, with supraumbilical and
      contralateral lower quadrant placement of the trocars. The Harmonic scalpel was
      used to fulgurate the spermatic vessels in a nonartery sparing technique.
      RESULTS: Ten clinically significant varicoceles were identified in 9 patients,
      all of which were ligated with this technique. One patient was treated for
      bilateral varicoceles. Average operating room time was 53 minutes (range, 45 to
      65). All patients were discharged from the ambulatory surgery unit and returned
      to their regular physical activity within 2 weeks after surgery. Upon clinical
      reevaluation 6 weeks post surgery, there was no evidence of varicocele recurrence
      or hydrocele formation, and all patients were asymptomatic. CONCLUSIONS: Our 2
      port laparoscopic varicocelectomy is comparable to traditional open surgical
      approaches in recurrence and complication rates. This laparoscopic repair may be
      superior to open techniques in operating time, convalescence, and cosmesis. The
      procedure is easily mastered and does not require microsurgical skills.

PMID- 16882411
TI  - Bedside diagnostic laparoscopy in the intensive care unit: a 13-year experience.
AB  - BACKGROUND: Frequently, critically ill patients suffer from intraabdominal
      pathology, such as sepsis or ischemia, either as a cause of a critical illness or
      as a complication from another illness requiring an intensive care unit (ICU)
      admission. These complications are associated with high rates of morbidity and
      mortality (between 50% to 100%). The diagnosis of these problems can be difficult
      in these very ill patients because it may require transport of unstable patients
      to additional departments outside the ICU setting. One option in the diagnosis of
      these difficult patients is bedside laparoscopy, as it avoids patient transport,
      is very accurate, and maintains ICU monitoring. METHODS: From 1991 to 2003, 13
      patients underwent bedside diagnostic laparoscopy in the ICU to diagnose
      intraabdominal pathology in critically ill patients. All the procedures were done
      at the bedside in the ICU with the patient under local anesthesia and intravenous
      sedation. RESULTS: Mean procedure time was 36 minutes (range, 17 to 55). Mean
      patient age was 75.5 years (range, 56 to 86). There were 8 males and 5 females.
      Forty-six percent of the patients were diagnosed with mesenteric necrosis and
      died within 48 hours with no further testing or procedures. One patient with
      massive fecal contamination died the same day. Thirty percent of patients had a
      normal intraabdominal examination; of these, 2 died of unrelated illnesses and 2
      survived their nonabdominal illness. Fifteen percent were diagnosed with acute
      acalculous cholecystitis as a complication of their ICU illness, which resolved
      satisfactorily. No intraoperative complications occurred with the ICU procedure.
      CONCLUSION: Bedside diagnostic laparoscopy in the ICU is feasible, safe, and
      accurate in the assessment of possible intraabdominal problems in properly
      selected, critically ill patients.

PMID- 16882412
TI  - Topical treatment with oxaliplatin for the prevention of port-site metastases in
      laparoscopic surgery for colorectal cancer.
AB  - BACKGROUND: The development of port-site metastases following laparoscopic
      resection of various malignancies continues to be a disturbing issue for
      laparoscopic surgeons. Previous studies revealed promising results with
      oxaliplatin, a third-generation platinum compound, as a first-line treatment in
      advanced colorectal cancer. This study evaluates the effect of topical
      application of oxaliplatin on the development of port-site metastases in an
      experimental murine model. METHODS: Nineteen female BDIX rats (immunocompetent, 6
      weeks old) underwent a sham laparoscopic operation after 1 x 10(7) viable rat
      colon carcinoma viable cells (LMCR) had been injected into their peritoneal
      cavities. Three trocars (1 central camera port and 2 additional lateral ports)
      were introduced into the abdomen, and a pneumoperitoneum was created with carbon
      dioxide. Ten minutes after LMCR, cells were injected into the peritoneal cavity,
      the 2 lateral trocars were removed and carbon dioxide insufflation was maintained
      for an additional 5 minutes to allow for tumor cell seeding. Oxaliplatin (0.198
      mg/kg) was then topically applied to 1 trocar site intramuscularly, while the
      other site was left untreated. One week later, the animals were euthanized, and
      the port sites were histologically examined for evidence of metastases. RESULTS:
      The rate of tumor implantation at the muscle layer in control sites was 68%
      (13/19) compared with 37% (7/19) at oxaliplatin-treated sites (P = 0.1). Also, no
      significant differences were detected in port-site metastasis rates in other
      untreated layers of the abdominal wall. CONCLUSION: Intramuscular topical
      application of oxaliplatin may not decrease the incidence of port-site metastasis
      in a syngeneic animal model of colon cancer. Nevertheless, we can see the
      tendency of declination. Further studies are needed to better determine its
      possible therapeutic role in high-risk humans undergoing laparoscopic resection
      of colorectal malignancies.

PMID- 16882413
TI  - Laparoscopic surgery for diverticular disease complicated by fistulae.
AB  - OBJECTIVES: Elective laparoscopic surgery for recurrent, uncomplicated
      diverticular disease is considered safe and effective; however, little data exist
      on complicated cases. We investigated laparoscopic sigmoid resection for
      diverticulitis complicated by fistulae. METHODS: We conducted a retrospective
      review of patients who underwent laparoscopic treatment of enteric fistulae
      complicating diverticular disease performed by 4 surgeons at the Mount Sinai
      Medical Center. RESULTS: From 1994 to 2004, 14 patients underwent elective
      laparoscopic sigmoid resections for diverticular disease complicated by enteric
      fistulae. Patients' mean age was 62 and 4 were female. Multiple fistulae were
      present in 21%. Types of fistulae included 8 colovesical, 5 enterocolic, 2
      colovaginal, 1 colosalpingal, and 1 colocutaneous. All patients successfully
      underwent sigmoidectomy, and 14% required additional bowel resections. No cases
      were proximally diverted. Conversion to open was necessary in 36% of cases, all
      due to dense adhesions and severe inflammation. The mean operative time was 209
      minutes, and the mean blood loss was 326 mL. Two (14%) postoperative
      complications occurred, including one anastomotic bleed and one prolonged ileus.
      No anastomotic leaks or mortalities occurred. The mean postoperative stay was 6
      days. CONCLUSION: Laparoscopic management of diverticular disease complicated by
      fistulae can be performed effectively and safely. The conversion rate is higher
      than traditionally accepted rates of uncomplicated cases of diverticulitis and is
      associated with severe adhesions and inflammation.

PMID- 16882414
TI  - The influence of prior abdominal operations on conversion and complication rates
      in laparoscopic colorectal surgery.
AB  - BACKGROUND AND OBJECTIVES: A history of a prior abdominal operation is common
      among patients presenting for laparoscopic colorectal surgery, and its impact on
      conversion and complication rates has been insufficiently studied. This study
      compares the conversion rates of patients with and without a prior abdominal
      operation (PAO). METHODS: We analyzed 1000 consecutive laparoscopic colorectal
      resection cases. RESULTS: Complete data on past surgical history were available
      on 820 of 1000 patients. The overall conversion rate was 14.8% (122/820). A
      history of PAO was present in 347 patients (42.3%). These patients experienced a
      higher conversion rate compared with non-PAO patients (68/347, 19.6% versus
      54/473, 11.4%; P < 0.001; OR 1.9). Patients with PAO had a significantly higher
      rate of inadvertent enterotomy (5/347, 1.4% vs. 1/473, 0.2%; P = 0.04; OR 6.9), a
      higher incidence of postoperative ileus (23/347, 6.6% vs 14/473% 3.0; P = 0.012;
      OR 2.3), and higher reoperative rates (8/347, 2.3% vs 1/473, 0.2%; P = 0.006; OR
      11.1). The incidence of other complications and mortality (total 6/820, 0.7%) was
      similar regardless of PAO status. CONCLUSION: Having a prior abdominal operation
      represents a risk factor for conversion in laparoscopic colon and rectal surgery.
      The incidence of a successfully completed laparoscopic operation, however,
      remains high in previously operated on patients.

PMID- 16882416
TI  - Preservation of an aberrant left hepatic artery during laparoscopic nissen
      fundoplication.
AB  - OBJECTIVE: Laparoscopic Nissen fundoplication is performed in neonates and
      children for significant gastroesophageal reflux. An aberrant left hepatic artery
      encountered during laparoscopic Nissen fundoplication makes dissection around the
      esophageal hiatus more difficult if the artery is not transected. Although some
      suggest division of the aberrant left hepatic artery, this is associated with
      risk of significant hepatic injury from ischemia. We routinely preserve the
      aberrant left hepatic artery and sought to determine (1) the incidence of
      aberrant left hepatic artery and (2) the results following preservation of the
      aberrant left hepatic artery. METHODS: Between January 2000 and October 2002, 195
      laparoscopic Nissen fundoplications were performed. We documented intraoperative
      findings of each procedure, and reviewed postoperative radiographic studies and
      clinic visits. RESULTS: In 30 patients (15%), an aberrant left hepatic artery was
      identified. All dissections were performed laparoscopically with the Nissen
      fundoplication positioned cephalad to the aberrant left hepatic artery.
      Postoperatively, 2 patients (6%) have had evidence of wrap failure. The remainder
      of the patients has had normal radiographic studies or no clinical evidence of
      reflux during clinic visits. CONCLUSION: During laparoscopic Nissen
      fundoplication in neonates and children, an aberrant left hepatic artery may be
      encountered in approximately 15% of patients. When an aberrant left hepatic
      artery is identified, it should be preserved to avoid the potential risk of
      hepatic ischemic injury.

PMID- 16882415
TI  - Laparoscopic Roux-en-Y Gastric bypass utilizing the triple stapling technique.
AB  - OBJECTIVE: To evaluate the outcomes of a single surgeon's experience with
      laparoscopic Roux-en-Y gastric bypass (LRYGB) utilizing the triple stapling
      technique for creation of the jejunojejunostomy. METHODS: A retrospective review
      of patients who underwent LRYGB utilizing the triple stapling technique for
      creation of the jejunojejunostomy (JJ) between 10/01 and 12/04 was performed.
      RESULTS: LRYGB was performed in 435 consecutive patients. The mean age was 41
      years (range, 14 to 68), and 82% were female. Mean initial body mass index was 50
      (range, 35 to 91). One conversion to open (0.2%) was necessary. Mean operating
      time was 144+/-26 minutes. Mean length of stay was 2.3+/-1.5 days. There were 3
      leaks at the gastrojejunostomy anastomosis (0.7%). No leaks occurred at the JJ
      anastomosis. One patient underwent revision of the JJ (0.2%) secondary to
      obstruction of the JJ on upper gastrointestinal study. Intraluminal bleeding
      occurred in 21 patients (4.8%). Patients required blood transfusion of 2.2+/-1.1
      units (range, 0 to 5), but none required surgical or endoscopic intervention.
      Mortality occurred in 2 patients (0.5%). Mean excess body weight loss was 72% at
      1 year. CONCLUSION: Construction of the jejunojejunostomy utilizing the triple
      stapling technique is expeditious, safe, and associated with minimal
      complication.

PMID- 16882417
TI  - Early results of the use of acellular dermal allograft in type III paraesophageal
      hernia repair.
AB  - BACKGROUND: Type III paraesophageal hernias are diaphragmatic defects with the
      risk of serious complications. High recurrence rates associated with primary
      suture repair are significantly improved with the use of a tension-free repair
      with prosthetic mesh. However, mesh in the hiatus is associated with multiple
      complications. A bio-engineered material from donated human tissue offers an
      attractive alternative material for hernia repair. This report is on the first
      series of laparoscopic type III paraesophageal hernia repairs with acellular
      dermal allografts (Allo-Derm, Lifecell Corporation, Branchburg, NJ) in 11
      patients with follow-up evaluation. METHODS: From August 2003 to June 2004, 11
      patients underwent laparoscopic repair of type III paraesophageal hernias with
      acellular dermal allografts. Patients were evaluated postoperatively with a
      symptoms questionnaire and barium esophagram. RESULTS: All patients were
      available for follow-up; however, 2 refused a barium esophagram. Average length
      of hospital stay was 3 days. Follow-up evaluation was at a mean interval of 1
      year. Postoperatively, 9 of 11 patients reported no symptoms. Barium esophagram
      revealed one recurrence in an asymptomatic patient. CONCLUSION: Type III
      paraesophageal hernia can be laparoscopically repaired successfully with
      acellular dermal allografts.

PMID- 16882418
TI  - A comparative study of routine laparoscopic versus open appendectomy.
AB  - OBJECTIVE: We evaluated the outcomes of routine laparoscopy and laparoscopic
      appendectomy (LA) in patients with suspected appendicitis. This is a
      retrospective study of the outcomes of patients undergoing laparoscopic
      appendectomy compared with outcomes for patients undergoing open appendectomy
      (OA) during the time that LA came into use. METHOD: Results of patients managed
      with routine laparoscopy and LA for suspected acute appendicitis were reviewed
      and analyzed. The preoperative and intraoperative findings were recorded. The
      clinical outcomes were compared with those of patients undergoing OA in the
      preceding 10 months. RESULTS: During the LA study period, 97 patients (47 men)
      with the median age of 34 years (range, 18 to 79) presented with clinical
      features of acute appendicitis. With the exclusion of 5 patients with open
      operations and 10 patients with other pathologies, 82 patients underwent
      laparoscopic appendectomy (Group A) for appendicitis. Thirty-one (37.8%) patients
      had complicated appendicitis (perforated or gangrenous appendicitis). Conversions
      were required in 6 patients (7.3%). During the OA period, 125 patients (57 men)
      with the median age of 42 (range, 19 to 79) years were operated on. With the
      exclusion of 6 patients with other pathologies, 119 underwent OA for acute
      appendicitis (Group B). Fifty-one (42.9%) had either perforated or gangrenous
      appendicitis. The median durations of surgery in Group A and Group B were 80
      minutes (range, 40 to 195) and 60 minutes (range, 25 to 260), respectively (P <
      0.005). Postoperative complication rates were comparable between the 2 groups
      (13.4% in Group A versus 15.8% in Group B). The median hospital stay for patients
      in Group A and Group B were 3.0 days (range, 1 to 47) and 4.0 days (range, 1 to
      47), respectively (P = 0.037). CONCLUSIONS: We conclude that routine laparoscopy
      and LA for suspected acute appendicitis is safe and is associated with a
      significantly shorter hospital stay. Other intra-abdominal pathologies can also
      be diagnosed more accurately with the laparoscopic approach.

PMID- 16882419
TI  - Laparoscopic transabdominal preperitoneal repair of spigelian hernia.
AB  - BACKGROUND: A Spigelian hernia is a congenital defect in the transversus
      aponeurosis fascia. Traditionally, an anterior hernioplasty was used to repair
      these defects. This study aimed to document our experience with laparoscopic
      transabdominal preperitoneal repair for Spigelian hernia. METHODS: Eight patients
      underwent laparoscopic transabdominal Spigelian hernia repair. All patients
      underwent creation of a peritoneal flap, sac dissection, identification and
      approximation of the fascial defect, mesh reinforcement, and reperitonealization.
      RESULTS: All patients presented with pain. An intermittent palpable mass was
      noticed in 4 patients. One third of the patients had undergone prior surgery and
      none had an incisional hernia. Only 1 patient presented with severe pain for 1
      day; however, there was no bowel strangulation intraoperatively. All patients
      underwent laparoscopic transabdominal preperitoneal repair. No postoperative
      complications occurred. There have been no recurrences at a mean follow-up of 41
      months (range, 8 to 96). CONCLUSION: Laparoscopic transabdominal preperitoneal
      repair of Spigelian hernia is safe, easy, and feasible for experienced
      laparoscopic surgeons.

PMID- 16882421
TI  - Endoscopic transaxillary near total thyroidectomy.
AB  - BACKGROUND: Since first reported in 1996, endoscopic minimally invasive surgery
      of the cervical region has been shown to be safe and effective in the treatment
      of benign thyroid and parathyroid disease. The endoscopic transaxillary technique
      uses a remote lateral approach to the thyroid gland. Because of the perceived
      difficulty in accessing the contralateral anatomy of the thyroid gland, this
      technique has typically been reserved for patients with unilateral disease.
      OBJECTIVES: The present study examines the safety and feasibility of the
      transaxillary technique in dissecting and assessment of both thyroid lobes in
      performing near total thyroidectomy. METHODS: Prior to this study we successfully
      performed endoscopic transaxillary thyroid lobectomy in 32 patients between
      August 2003 and August 2005. Technical feasibility in performing total
      thyroidectomy using this approach was accomplished first utilizing a porcine
      model followed by three human cadaver models prior to proceeding to human
      surgery. After IRB approval three female patients with histories of enlarging
      multinodular goiter were selected to undergo endoscopic near total thyroidectomy.
      RESULTS: The average operative time for all models was 142 minutes (range 57-327
      min). The three patients in this study had clinically enlarging multinodular
      goiters with an average size of 4 cm. The contralateral recurrent laryngeal nerve
      and parathyroid glands were identified in all cases. There was no post-operative
      bleeding, hoarseness or subcutaneous emphysema. CONCLUSION: Endoscopic
      transaxillary near total thyroidectomy is feasible and can be performed safely in
      human patients with bilateral thyroid disease.

PMID- 16882420
TI  - Laparoscopic splenectomy in the management of benign and malignant hematologic
      diseases.
AB  - OBJECTIVES: The use of laparoscopy to treat malignant hematological diseases is
      not completely accepted. Our aim was to analyze operative and postoperative
      results of laparoscopic splenectomy performed for benign versus malignant
      hematological disorders. METHODS: Between 1994 and 2003, 76 consecutive patients
      underwent laparoscopic splenectomy. The first 38 cases were performed by using an
      anterior approach, whereas in the remaining 38 cases a semilateral position was
      used. RESULTS: Baseline characteristics showed that patients with malignant
      diseases were significantly older (56.9 vs 32.6 years, P < 0.001). Seventy-two
      (94.7%) procedures were completed laparoscopically. Conversion was required in 4
      cases (5.2%). Mean operative time was 138.5 minutes for benign and 151.0 minutes
      for malignant diseases, (P > 0.05, ns). The hand-assisted technique was used in 3
      patients with massive splenomegaly. Pathologic features showed that spleen volume
      was higher in patients with malignant diseases (mean interpole diameter 18.1 cm
      vs 13.7 cm, P < 0.001). Massive splenomegaly (interpole diameter over 20 cm,
      weight over 1000 g) was present in 13 patients (17.1%); 9 had malignant diseases.
      Overall perioperative mortality was 1.3% and major postoperative complications
      occurred in 6 patients (7.8%). Postoperative splenoportal partial thrombosis was
      identified in 9.7% of patients. CONCLUSIONS: Laparoscopic splenectomy is a well
      accepted, less-invasive procedure for hematological disorders. Neoplastic
      diseases or splenomegaly, or both, do not seem to limit the indications for a
      minimally invasive approach after the learning curve.

PMID- 16882422
TI  - Hernias as a cause of chronic pelvic pain in women.
AB  - BACKGROUND: Chronic pelvic pain in women due to hernias may be misdiagnosed by
      practicing clinicians. These fascial defects, their symptoms, physical findings,
      and proper treatment must be known in order to help women experiencing this form
      of chronic pelvic pain. METHODS: All procedures were performed by the primary
      author using standard laparoscopic tension-free mesh techniques. RESULTS: The
      study included 264 patients referred to a chronic pelvic pain clinic, who
      underwent 386 laparoscopic surgical repairs of hernial defects. Ninety percent of
      the patients underwent concomitant procedures appropriate for their multiple pain
      generators. Length of follow-up is 1.53 years (range, 2 months to 5.5 years).
      Evaluation of patients' pain component from the repaired hernia was recorded.
      There have been no recurrences. One persistent ilioinguinal neuropathy from an
      inguinal hernia repair (.4%) has occurred. All other patients received relief of
      their hernia pain (99.6%). Four complications from concomitant surgeries (1.5%)
      are reported. CONCLUSIONS: Laparoscopic treatment of hernia pain in women is
      effective in relieving chronic pain and has a low recurrence and complication
      rate in the hands of experienced laparoscopists.

PMID- 16882423
TI  - Predictive value of magnetic resonance imaging in differentiating between
      leiomyoma and adenomyosis.
AB  - OBJECTIVE: We evaluated the role of MRI as a preoperative diagnostic tool for
      leiomyoma and adenomyosis. METHOD: This is a retrospective chart review at a
      university-based hospital. The study included 1517 women who underwent
      hysterectomy or myomectomy over a 5-year period, and 153 women with a
      preoperative pelvic MRI were included. Comparisons were made between the results
      of the MRI and postoperative pathology reports. RESULTS: The MRI and pathology
      report were the same for 136 of 144 women with leiomyoma and 12 of 31 women with
      adenomyosis. The MRI had 94% sensitivity and 33% specificity for leiomyoma and
      38% sensitivity and 91% specificity for adenomyosis. Positive and negative
      predictive values of MRI for leiomyoma were 95% and 27% with 90% accuracy.
      Positive and negative predictive values of MRI for adenomyosis were 52% and 85%,
      respectively, with 80% accuracy. CONCLUSION: MRI has a high sensitivity and a low
      specificity for diagnosing leiomyoma and a high specificity and a low sensitivity
      for diagnosing adenomyosis. Due to the high cost and technical variations, we
      suggest using MRI only as an adjunctive diagnostic tool when ultrasound is not
      conclusive and differentiation between the 2 pathologies ultimately affects
      patient management.

PMID- 16882424
TI  - Laparoscopic removal of pubovaginal polypropylene tension-free tape slings.
AB  - OBJECTIVES: Complications of polypropylene pubovaginal tension-free tape slings
      (TVT, SPARC, and others), such as erosion into the bladder or chronic pain
      attributed to the mesh sling are rare events; however, when they occur, it may
      necessitate removal of the sling. To date, removal through a laparotomy incision
      or by operative cystoscopy has been the most common approach. We present 5 cases
      of a laparoscopic approach for removal of polypropylene pubovaginal tension-free
      tape slings. METHODS: We report 5 cases of laparoscopic removal of TVT mesh.
      Three were removed for mesh erosion into the bladder, and 2 were removed
      secondary to the patients having persistent pain and discomfort attributed to the
      sling. An intraperitoneal approach was used to enter the retropubic space to
      remove the sling. Dissection was completed with a Harmonic scalpel blade as well
      as blunt dissection to identify the mesh sling retropubically. Average operating
      time was 104 minutes. Average blood loss was 70 mL. Average hospital stay was <23
      hours. Postoperative courses were uneventful; however, 4 of the 5 patients
      continue to have urgency and frequency symptoms following sling removal.
      CONCLUSION: These cases illustrate the use of laparoscopy in the removal of
      polypropylene pubovaginal tension-free tape slings for bladder erosion or
      persistent pain, or both, attributed to the sling. Erosion and pain are known
      complications of polypropylene pubovaginal slings and may cause significant
      morbidity like persistent detrusor instability or urge incontinence, or both.
      Patients must be informed of these risks and possible complications before making
      their decision to undergo surgery.

PMID- 16882425
TI  - Comparison of cervical detachment using monopolar lap loop ligature and
      conventional methods in laparoscopic supracervical hysterectomy.
AB  - OBJECTIVES: Our aim was to evaluate a new electrosurgical instrument (Lap Loop
      device) that amputates the uterine corpus from the cervix during a laparoscopic
      supracervical hysterectomy (LSH) and to compare the time required for cervical
      amputation with traditional methods. METHODS: This comparative trial was
      conducted at the University of Louisville and Norton Healthcare Hospitals,
      Louisville, KY. The patients comprised 29 women scheduled for hysterectomy for
      benign conditions. All patients underwent laparoscopic supracervical
      hysterectomy. The Lap Loop device was used in 17 patients to section the cervix.
      Conventional methods with either laparoscopic monopolar scissors or Harmonic
      scalpel were used in 12 patients. RESULTS: In the control group, the mean
      cervical cutting time with laparoscopic scissors or Harmonic scalpel was 14.4
      minutes. The mean time for the application of the loop electrode and cutting time
      was 6.6 minutes and was significantly shorter than the cutting time of
      conventional methods. Two minor complications (7.4% of cases) and one relatively
      major complication (3.7%), an incisional hernia, occurred in the study patients.
      None of the complications were related to the new device. CONCLUSION: An
      electrosurgical loop decreased the time required for resection of the uterine
      cervix during LSH for benign uterine conditions. This device facilitates and
      increases the safety of this procedure.

PMID- 16882426
TI  - Diagnostic hysteroscopy as a primary tool in a basic infertility workup.
AB  - OBJECTIVE: To assess the value of diagnostic hysteroscopy in a primary workup of
      infertility. METHODS: We performed a retrospective analysis (Canadian Task Force
      Classification II-2) of 221 infertile patients referred to the Outpatient Center
      for Uterine Cavity Evaluation and the Tel-Aviv University affiliated Assaf Harofe
      Medical Center for evaluation of the uterine cavity. Patients underwent a
      diagnostic office hysteroscopy. RESULTS: Hysteroscopy revealed an abnormal
      uterine cavity in 30% of women evaluated for either primary or secondary
      infertility. No significance was found regarding the total number of intrauterine
      pathologies when comparing the groups of primary versus secondary infertility.
      CONCLUSION: Routine diagnostic hysteroscopy should be part of an infertility
      workup in primary and secondary infertility.

PMID- 16882427
TI  - Intestinal ischemia after laparoscopic cholecystectomy.
AB  - OBJECTIVES: Intestinal ischemia is a rarely reported complication following
      laparoscopic cholecystectomy. We describe a case of massive small intestinal
      necrosis 3 days following this procedure. An autopsy determined the cause to be
      splanchnic hypoperfusion, likely due to the physiologic changes induced by the
      pneumoperitoneum necessary to conduct the surgery. We sought to determine whether
      all reported cases of intestinal ischemia following laparoscopic cholecystectomy
      (LC) shared the same etiology, and if faulty operative technique could be
      invoked. METHODS: A review of all known published cases of intestinal ischemia
      following LC was conducted to determine the underlying etiology of ischemia, and
      whether adequate operative technique had been observed. RESULTS: Multiple causes
      of intestinal ischemia following LC have been described: splanchnic
      hypoperfusion, thrombosis of the superior mesenteric artery, and thrombosis of
      the inferior mesenteric vein. All occurred despite correct operative technique.
      CONCLUSIONS: Intestinal ischemia following LC has diverse causes. Patient factors
      rather than faulty operative technique would appear to underlie the development
      of this rare complication.

PMID- 16882428
TI  - Management options of colonoscopic splenic injury.
AB  - Injury to the spleen during routine colonoscopy is an extremely rare injury.
      Diagnosis and management of the injury has evolved with technological advances
      and experience gained in the management of splenic injuries sustained in trauma.
      Of the 37 reported cases of colonoscopic splenic injury, 12 had a history of
      prior surgery or a disease process suggesting the presence of adhesions. Only 6
      had noted difficulty during the procedure, and 31 patients experienced pain,
      shock, or hemoglobin drop as the indication of splenic injury. Since 1989, 21/24
      (87.5%) patients have been diagnosed initially using computed tomography or
      ultrasonography. Overall, only 27.8% have retained their spleens. None have
      experienced as long a delay as our patient, nor have any had an attempt at
      percutaneous control of the injury. This report presents an unusual case of a
      rare complication of colonoscopy and the unsuccessful use of one nonoperative
      technique, and reviews the experience reported in the world literature, including
      current day management options.

PMID- 16882429
TI  - Laparoscopic gastric wedge resection for Dieulafoy's disease following
      preoperative endoscopic localization with India ink and endoscopic clips.
AB  - BACKGROUND: Dieulafoy's lesion is a vascular malformation, usually of the stomach
      but occasionally of the small or large bowel. It is an uncommon, but clinically
      significant, source of upper gastrointestinal hemorrhage. Three cases have been
      reported in the literature of laparoscopic gastric wedge resection of these
      lesions by using intraoperative endoscopic localization. We present the only
      reported case of preoperative endoscopic localization of a Dieulafoy's lesion
      with India ink and an endoscopic clip before laparoscopic resection. CASE REPORT:
      We present an 82-year-old female patient who presented to the emergency
      department with 3 episodes of hematemesis. Esophagogastroduodenoscopy revealed an
      actively bleeding Dieulafoy's lesion in the fundus of the stomach along the
      greater curvature, which was controlled endoscopically. However, the patient had
      a recurrent episode of bleeding. Repeat endoscopy was performed and the lesion
      was tagged with 2 endoscopic clips and marked with India ink. A laparoscopic
      wedge resection was performed after the India ink was identified in the fundus.
      The patient did well postoperatively. CONCLUSION: Preoperative localization of a
      Dieulafoy's lesion with India ink and endoscopic clips before laparoscopic wedge
      resection is a feasible procedure. Therefore, no need exists for intraoperative
      endoscopy to aid in the localization, as previously reported.

PMID- 16882430
TI  - A spiral tack as a lead point for volvulus.
AB  - BACKGROUND AND OBJECTIVES: We present a case of small bowel volvulus around an
      endotack applied during total extraperitoneal laparoscopic hernia repair (TEP).
      This complication prompts reconsideration of the role of tacks during
      extraperitoneal laparoscopic hernia repairs. METHODS: We undertook a chart review
      and provide a case presentation with review of the literature. RESULT: A 66-year
      old male with bilateral inguinal hernias underwent elective, bilateral, total
      extraperitoneal laparoscopic hernia repair. During dissection, a small peritoneal
      tear occurred. The tear was closed with a spiral tack. On postoperative day 22,
      the patient developed an acute abdomen. Exploratory laparotomy revealed a
      volvulus rotated around an adhesion to the spiral tack. DISCUSSION: Volvulus can
      cause vascular compromise leading to bowel ischemia and necrosis. A tack
      resulting in adhesion and volvulus is an unusual, but serious, complication.
      Repair of a peritoneal tear during preperitoneal hernia repair is advocated to
      improve visualization obstructed by a pneumoperitonuem and decrease adhesions to
      the abdominal wall. CONCLUSION: The use of blunt Endoloops or crimps may prove
      safer than tacks for repairing the peritoneum and placement in proximity to
      delicate or thin tissues. Additionally, careful placement of foreign bodies to
      ensure their stability and to minimize protrusion may decrease the risk of
      erosion of the hardware.

PMID- 16882431
TI  - Ileocecal intussusception in an adult: the laparoscopic approach.
AB  - Adult intussusception is uncommon and requires a surgical approach. Malignancy is
      associated with 31% (43/137) of small bowel intussusception and 70% (74/106) of
      large bowel intussusception. Computerized tomography (CT) findings are
      pathognomonic for this condition. Often, the patient presents with long-standing,
      nonspecific complaints. A 63-year-old man presented with sudden onset of
      abdominal pain. CT demonstrated colonic inflammation. A laparoscopic right
      hemicolectomy for ileocecal intussusception was performed. The pathology report
      revealed a lipoma of the cecum. The postoperative course was uneventful, and he
      was discharged the fifth postoperative day. Despite a high incidence of
      malignancy, colonic or ileocecal intussusception can be successfully treated by
      laparoscopic resection. Review of the literature and treatment options are
      discussed.

PMID- 16882432
TI  - Laparoscopic management of giant ovarian cyst.
AB  - INTRODUCTION: Giant intraabdominal cysts are very rare, and conventional
      treatment is full midline laparotomy. We present a case of complete laparoscopic
      extirpation of a giant ovarian cyst. CASE REPORT: A 16-year-old female presented
      with progressive abdominal distension for 1-year along with early satiety,
      constipation, and significant weight loss. A CT scan showed a giant multiseptated
      cystic mass in the abdomen measuring 22.5 x 30 x 40.5 cm with significant mass
      effect causing intrahepatic ductal dilatation and right hydronephrosis. The mass
      was decompressed via a mini-laparotomy in a controlled fashion, removing 15
      liters of fluid. A laparoscopic left oophorectomy was then performed. The
      postoperative course was uneventful, and the patient was discharged home on
      postoperative day 1 with minimal pain and tolerating a regular diet. Pathology
      examination revealed a mature cystic teratoma. CONCLUSION: Giant ovarian cysts
      can be managed laparoscopically when a normal tumor marker profile and benign
      imaging appearance exclude the possibility of malignancy.

PMID- 16882433
TI  - Laparoscopic removal of a rudimentary uterine horn in a previously
      hysterectomized patient.
AB  - BACKGROUND: The unicornuate uterine anomaly is often difficult to diagnose and
      usually low on the list of differential diagnoses for pelvic pain and
      dysmenorrhea. The authors present a case of a rudimentary uterine horn as a cause
      for continued pelvic pain and dysmenorrhea in a previously hysterectomized woman.
      CASE REPORT: A 43-year-old woman, gravida 1, para 1, presented for evaluation of
      right lower quadrant pain of several years' duration. Her past surgical history
      was significant for multiple prior laparoscopies and a vaginal hysterectomy.
      Radiographic studies revealed a mass in the right lower quadrant. Laparoscopy
      revealed a solid mass in the right pelvis that was diagnosed as a rudimentary
      uterine horn. CONCLUSION: Uterine anomalies, although uncommon, should be thought
      of as part of the differential diagnosis for pelvic pain and dysmenorrhea. A
      thorough inspection of the pelvis should be performed at the time of any
      operative procedure for abdominal pain.

PMID- 16882434
TI  - Laparoscopic enucleation of a nonfunctioning neuroendocrine tumor at the head of
      the pancreas.
AB  - OBJECTIVE: Laparoscopy is a safe, feasible technique for benign pancreatic
      pathologies and has been increasingly reported for neuroendocrine tumors located
      at the body and tail of the pancreas. We report a case of successful enucleation
      of a nonfunctioning neuroendocrine tumor located at the head of the pancreas, in
      a patient with multiple endocrine neoplasia type I. METHODS: A 5-cm
      nonfunctioning neuroendocrine tumor at the pancreatic head was identified by
      computerized tomography scan. Laparoscopic ultrasound did not reveal additional
      tumors on any other part of the pancreas. RESULTS: Enucleation was successfully
      performed for this solitary tumor because of its favorable position. Histology
      revealed an islet cell tumor. No postoperative complications occurred and
      recovery was rapid. CONCLUSION: Laparoscopic enucleation of neuroendocrine tumor
      at the pancreatic head is safe and feasible for select patients.

PMID- 16882435
TI  - Laparoscopic treatment of hypertension after micturition: Bladder
      pheochromocytoma.
AB  - Bladder pheochromocytomas are extremely rare and constitute less than 5% of
      bladder tumors. The initial symptoms of the patient are mostly nonspecific caused
      by hypertension. The postmicturition hypertensive crisis is the typical warning
      sign of this disease. In this article, we present a 29-year-old female having
      hypertensive attacks following micturition. Radiological imaging techniques
      revealed a 3 x 3 x 4-cm bladder tumor that was hormonally active. This is the
      first case reported of bladder pheochromocytoma that was laparoscopically treated
      without using the adjunct transurethral resection. The postoperative follow-up of
      the patient confirms the success of the surgical procedure.

PMID- 16882436
TI  - Microlaparoscopic-assisted lumboperitoneal shunt in the lateral position for
      pseudotumor cerebri in a morbidly obese adolescent.
AB  - BACKGROUND: Pseudotumor cerebri or idiopathic intracranial hypertension is a
      known complication of morbid obesity that often requires neurosurgical
      intervention for worsening symptoms. Placement of a lumboperitoneal shunt (LPS)
      is one of the treatment options, but in a morbidly obese patient it can be
      technically challenging. We describe the use of 3-mm instrumentation for
      assistance in placing the peritoneal end of the shunt. CASE REPORT: A 16-year-old
      morbidly obese girl with a diagnosis of pseudotumor cerebri and decreasing visual
      acuity and contraction of her visual fields underwent lumboperitoneal shunt
      placement. Due to her body habitus secondary to her morbid obesity a
      microlaparoscopic-assisted approach was utilized for placement of the peritoneal
      end of the lumboperitoneal shunt. RESULTS: No operative or postoperative problems
      occurred, and she was discharged home with resolution of symptoms. Her visual
      acuity and fields had normalized at 3-month follow-up. CONCLUSION:
      Microlaparoscopic-assisted lumboperitoneal shunt placement in the lateral
      position is an efficient and safe method for the treatment of pseudotumor
      cerebri. It is a minimally invasive, simple, effective tool for placing the
      peritoneal catheter for LPS.

PMID- 16882437
TI  - Laparoscopy in afferent loop obstruction presenting as acute pancreatitis.
AB  - BACKGROUND: We describe an afferent loop obstruction caused by an adhesion band
      in a case of distal gastrectomy with Roux-en-Y end-to-side jejunal anastomosis
      for cancer. METHODS: An initial clinical presentation of acute pancreatitis was
      ruled out by a computed tomography scan, which revealed intestinal obstruction;
      it was then confirmed on laparoscopy. Definitive treatment was laparoscopic
      adhesiolysis. A complete review of the literature concerning afferent loop
      obstructions is presented. RESULTS: The treatment was successful, with minimal
      postoperative pain, and the 5-day hospital stay was uncomplicated. The patient
      remains asymptomatic at 1-year follow-up. CONCLUSIONS: The authors advocate
      minimally invasive surgery as a complete diagnostic and therapeutic alternative
      to emergency laparotomy in cases where afferent loop syndrome is suspected, and
      acknowledge that prompt surgery has a higher rate of success and reduces
      operative morbidity and mortality.

PMID- 16882438
TI  - Biography of Camran Nezhat, MD, FACOG, FACS.

PMID- 16882439
TI  - Knee osteoarthritis: should your patient opt for hyaluronic acid injection?

PMID- 16882440
TI  - Itching and rash in a boy and his grandmother.

PMID- 16882441
TI  - Dealing with school refusal behavior: a primer for family physicians.

PMID- 16882442
TI  - "Hot tub" lung: Is it on your list of respiratory ailments?

PMID- 16882443
TI  - Patients with needle phobia? Try stress-reducing medical devices.

PMID- 16882445
TI  - Clinical inquiries. Which medications can be split without compromising efficacy
      and safety?
AB  - Split tablets of lisinopril are as effective as whole tablets of the same dose
      for hypertension (strength of recommendation [SOR]: B, based on small randomized
      crossover study). Similarly, split tablets of atorvastatin, lovastatin, and
      simvastatin are no less effective for lowering cholesterol (SOR: B, based on
      retrospective cohort studies). Extended-release, enteric-coated, or tablets that
      cannot be split accurately are not appropriate for splitting (SOR: C, based on
      observational studies); the accuracy of splitting also depends on device used and
      user skill (SOR: C, based on observational study).

PMID- 16882444
TI  - Malpractice crisis: causes of escalating insurance premiums, and implications for
      you.

PMID- 16882446
TI  - Clinical inquiries. Which vaccinations are indicated after splenectomy?
AB  - Immunization against encapsulated bacterial pathogens decreases the incidence of
      post-splenectomy sepsis. Pneumococcal, meningococcal, and Haemophilus influenzae
      (Hib) vaccinations are indicated for patients after splenectomy. These
      immunizations should be given at least 14 days before a scheduled splenectomy, or
      given after the fourteenth postoperative day (strength of recommendation [SOR]:
      A, based on systematic review of RCTs for the pneumococcal vaccine; SOR: B, based
      on systematic review of clinical trials for meningococcal and Hib vaccines).

PMID- 16882447
TI  - Clinical inquiries. What is the most effective management of acute fractures of
      the base of the fifth metatarsal?
AB  - For acute Jones' fractures in recreationally active patients, early
      intramedullary screw fixation results in lower failure rates and shorter times to
      both clinical union and return to sports than non-weightbearing short leg casting
      (strength of recommendation [SOR]: A, based on 2 randomized controlled trials
      [RCT]). Non-weightbearing short leg casting achieves union in 56% to 100% of
      patients but can require prolonged casting (SOR: B, based on 2 prospective
      cohorts and multiple retrospective, follow-up studies). Stress fractures were not
      included in this review. For avulsion fractures of the fifth metatarsal
      tuberosity, a soft Jones' dressing allows earlier return to pre-injury levels of
      activity than rigid short leg casting (SOR: B, based on a lower-quality RCT).

PMID- 16882448
TI  - Clinical inquiries. How should we manage a patient with a positive PPD and prior
      BCG vaccination?
AB  - Prior bacille Calmette-Guerin (BCG) vaccination increases the likelihood of a
      positive tuberculosis (TB) 5TU purified protein derivative (PPD) skin test. The
      PPD response following BCG vaccine varies with age at vaccination, number of
      years since the BCG vaccination, number of times vaccinated, and number of PPDs
      performed. An induration of greater than 14 mm is unlikely to be due to prior BCG
      vaccination (strength of recommendation [SOR]: A, based on meta-analysis of
      validation cohort studies). The variable reaction after BCG vaccination, along
      with the desire to detect all cases of TB, has led to recommendations that all
      patients with a positive PPD test be treated as true positives. These patients
      should undergo chest radiography and appropriate treatment, regardless of history
      of BCG vaccine (SOR: B, extrapolation from level 1 study). A recently developed
      alternative is the interferon-gamma assay (QuantiFERON-TB Gold test), which may
      be used in place of, or in addition to, the PPD skin test for patients who are
      known to have received a BCG vaccine (SOR: B, extrapolation from a validation
      cohort study).

PMID- 16882449
TI  - Clinical inquiries. When should we screen children for hyperlipidemia?
AB  - Children should be screened for hyperlipidemia when there is a history of
      familial hypercholesterolemia (strength of recommendation [SOR]: C). No clear
      evidence supports screening all children or just those with family history of
      cardiovascular disease (CVD) or hyperlipidemia (SOR: C).

PMID- 16882450
TI  - Clinical inquiries. What are contraindications to IUDs?
AB  - Based on limited evidence, use of intrauterine devices (IUDs) is not
      contraindicated for women with HIV/AIDS (strength of recommendation [SOR]: C),
      multiple sexual partners (SOR: C), previous actinomyces colonization (SOR: C),
      most types of fibroids (SOR: C), or previous ectopic pregnancy (SOR: C). The risk
      to IUD users of pelvic inflammatory disease (PID) is similar to women using no
      contraception (SOR: B). Nulliparous women may experience increased insertion
      discomfort and higher rates of expulsion (SOR: B). IUD use of <3.5 years is not
      associated with decreased fertility (SOR: B).

PMID- 16882451
TI  - Arsenic trioxide induces not only apoptosis but also autophagic cell death in
      leukemia cell lines via up-regulation of Beclin-1.
AB  - Although recent data shows that arsenic trioxide (As2O3) is capable of inducing
      cell death via cell cycle arrest and apoptosis both in acute promyelocytic
      leukemia (APL) and in non-APL cells, the mechanisms of As2O3-mediated cell death
      are not fully understood. In this study, we investigated the in vitro effects of
      As2O3 on cell growth inhibition and cell death in human T-lymphocytic leukemia
      and myelodysplastic syndrome (MDS) cell lines. As2O3 significantly inhibited the
      proliferation of Molt-4 and Mutz-1 cells in dose- and time-dependent manner.
      Autophagic cell death (programmed cell death type II) and apoptosis (programmed
      cell death type I) were activated together in leukemia cell lines after exposed
      to As2O3. Numerous large cytoplasmic inclusions and vacuoles were observed in
      As2O3-treated cells using electron microscope. Furthermore, 3-methyladenine (an
      autophagy inhibitor) significantly reduced autophagic cell death and sequentially
      induced apoptosis. Finally, leukemia cells treated with 4 microM As2O3 showed a
      considerable up-regulation of Beclin-1 (a Bcl-2-interacting protein) expression,
      which was independent of transcription of mRNA and required protein synthesis. In
      addition, Molt-4 cells treated with As2O3 exhibited the down-regulation of Bax
      protein expression, suggesting that Bax may be involved in accumulating of Beclin
      1 and triggering autophagic cell death in As2O3-treated leukemia cells. These
      results may lead to a better understanding of the mechanism of action of As2O3,
      and provide a suggestion that As2O3 may be of therapeutic value for the treatment
      of patients with human T-lymphocytic leukemia and myelodysplastic syndrome.

PMID- 16882452
TI  - Implications of the initial mutations in membrane cofactor protein (MCP; CD46)
      leading to atypical hemolytic uremic syndrome.
AB  - The hemolytic uremic syndrome is characterized by the triad of microangiopathic
      hemolytic anemia, thrombocytopenia and acute renal failure. There are two general
      types. One occurs in epidemic form and is diarrheal associated (D+HUS). It has a
      good prognosis. The second is a rare form known as atypical (aHUS), which may be
      familial or sporadic, and has a poor prognosis. aHUS is increasingly recognized
      to be a disease of defective complement regulation, particularly cofactor
      activity. Mutations in membrane cofactor protein (MCP; CD46) that predispose to
      the development of aHUS were first identified in 2003. MCP is a membrane-bound
      complement regulator that acts as a cofactor for the factor I-mediated cleavage
      of C3b and C4b deposited on host cells. More than 20 different mutations in MCP
      have now been identified in patients with aHUS. Many of these mutants have been
      functionally characterized and have helped to define the pathogenic mechanisms
      leading to aHUS development. Over 75% of the reported mutations cause a reduction
      in MCP expression, due to homozygous, compound heterozygous or heterozygous
      mutations. This deficiency of MCP leads to inadequate control of complement
      activation on endothelial cells after an initiating injury. The remaining MCP
      mutants are expressed, but demonstrate reduced ligand (C3b/C4b) binding capacity
      and cofactor activity of MCP. MCP mutations in aHUS demonstrate incomplete
      penetrance, indicating that additional genetic and environmental factors are
      required to manifest disease. MCP mutants as a cause of aHUS have a favorable
      clinical outcome in comparison to patients with factor H (CFH) or factor I (IF)
      mutations. In 90% of the renal transplants performed in patients with MCP-HUS,
      there has been no recurrence of the primary disease, whilst >50% of factor I or
      factor H deficient patients have had a prompt recurrence. This highlights the
      importance of defining and characterizing the underlying genetic defects in
      patients with aHUS.

PMID- 16882453
TI  - Innate immune response of bovine mammary gland to pathogenic bacteria responsible
      for mastitis.
AB  - Mastitis (mammary gland inflammation) is one of the most important bovine
      diseases causing economic losses to dairy producers. Mammary gland inflammation
      is a consequence of the activity of a number of cell and soluble factors that
      function together to eliminate invading microorganisms. The factors involved in
      this inflammatory response differ depending on the infectious agent. This review
      analyzes the factors involved in the immunologic mechanisms against the main
      pathogenic bacteria causing mastitis, and emphasizes the innate immune response
      of the mammary gland. Knowledge, at the molecular level, of the mammary gland
      immune response during infection by pathogenic bacteria is fundamental to the
      design of effective therapies to control and eradicate bovine mastitis.

PMID- 16882454
TI  - Capnocytophaga ochracea causing severe sepsis and purpura fulminans in an
      immunocompetent patient.
AB  - Capnocytophaga ochracea (C. ochracea), a known human microflora, has been
      reported to cause sepsis in immunocompromised patients and less severe infections
      such as intrauterine infections, endocarditis, peritonitis and septic arthritis
      in the immunocompetent patient. We present the first described case of C.
      ochracea causing severe sepsis and purpura fulminans in an immunocompetent host.

PMID- 16882455
TI  - Regulation of self-incompatibility by acetylcholine and cAMP in Lilium
      longiflorum.
AB  - Elongation of pollen tubes in pistils of Lilium longiflorum cv. Hinomoto after
      self-incompatible pollination was here found to be promoted by acetylcholine
      (ACh) and other choline derivatives, such as acetylthiocholine, l-alpha
      phosphatidylcholine and chlorocholinechloride [CCC; (2-chloroethyl) trimethyl
      ammonium chloride]. Moreover, the elongation was promoted by neostigmine, a
      potent inhibitor of acetylcholinesterase (AChE; acetylcholine-decomposing enzyme)
      (EC 3.1.1.7.) and activities of this and choline acetyltransferase (ChAT;
      acetylcholine-forming enzyme) (EC 2.3.1.6.) in pistils were associated with self
      incompatibility. The activity of ChAT was lower after self-incompatible as
      compared with cross-compatible pollination. Application of cAMP promoted ChAT
      activities in both cases, whereas activity of AChE in pistils after self
      pollination was higher than that after cross-compatible pollination and was
      suppressed by cAMP in both cases. Furthermore, AChE activity was inhibited by
      treatment with neostigmine or heating. Our results indicate that the self
      incompatibility with self-pollination is due to decrease of ACh and cAMP, causing
      reduction of ChAT and AC (adenylate cyclase) and concise elevation of AChE and
      PDE (cAMP phosphodiesterase), and therefore suppressed growth of pollen tubes.

PMID- 16882456
TI  - Identification of a novel Cys2/His2-type zinc-finger protein as a component of a
      spermine-signaling pathway in tobacco.
AB  - In a previous work, we identified a Cys(2)/His(2)-type zinc-finger transcription
      repressor, (ZFT1), that functions in a spermine-mediated signal transduction
      pathway in tobacco plants. Database search disclosed the presence of another
      Cys(2)/His(2)-type zinc-finger protein ZFP1 (accession number AAC06243) in
      tobacco plants. In this work, we characterized ZFP1 and investigated whether this
      protein is also involved in a Spm-signaling pathway. This factor showed the
      highest identity to petunia ZPT2-2 and higher similarity to petunia ZPT2-3,
      Arabidopsis STZ/ZAT10, soybean SCOF-1, red pepper CAZFP1/CaPIF1 as well as to
      tobacco ZFT1. ZFP1 localized to the nucleus and had a specific DNA-binding
      activity, supportive to be a transcription factor. Furthermore, the protein had a
      mild repression activity on transcription in plant cells. The expression of ZFP1,
      encoding ZFP1, was upregulated during tobacco mosaic virus-induced hypersensitive
      response. ZFP1 expression was also induced by exogenously applied spermine and
      its induction was repressed by inhibitors of amine oxidase/polyamine oxidase.
      Collectively, our data indicate that ZFP1 is a new transcription factor which
      functions in a spermine-signaling pathway in tobacco.

PMID- 16882457
TI  - Bioactive analogs of neurotensin: focus on CNS effects.
AB  - Neurotensin (NT) is a 13-amino acid neuropeptide found in the central nervous
      system and in the gastrointestinal tract. It is closely associated anatomically
      with dopaminergic and other neurotransmitter systems, and evidence supports a
      role for NT agonists in the treatment of various neuropsychiatric disorders.
      However, NT is readily degraded by peptidases, so there is much interest in the
      development of stable NT agonists, that can be injected systemically, cross the
      blood-brain barrier (BBB), yet retains the pharmacological characteristics of
      native NT for therapeutic use in the treatment of diseases such as schizophrenia,
      Parkinson's disease and addiction.

PMID- 16882458
TI  - Hyphenation of Raman spectroscopy with gravimetric analysis to interrogate water
      solid interactions in pharmaceutical systems.
AB  - A moisture sorption gravimetric analyzer has been combined with a Raman
      spectrometer to better understand the various modes of water-solid interactions
      relevant to pharmaceutical systems. A commercial automated moisture sorption
      balance was modified to allow non-contact monitoring of the sample properties by
      interfacing a Raman probe with the sample holder. This hybrid instrument allows
      for gravimetric and spectroscopic changes to be monitored simultaneously. The
      utility of this instrument was demonstrated by investigating different types of
      water-solid interactions including stoichiometric and non-stoichiometric hydrate
      formation, deliquescence, amorphous-crystalline transformation, and capillary
      condensation. In each of the model systems, sulfaguanidine, cromolyn sodium,
      ranitidine HCl, amorphous sucrose and silica gel, spectroscopic changes were
      observed during the time course of the moisture sorption profile. Analysis of
      spectroscopic data provided information about the origin of the observed changes
      in moisture content as a function of relative humidity. Furthermore, multivariate
      data analysis techniques were employed as a means of processing the spectroscopic
      data. Principle components analysis was found to be useful to aid in data
      processing, handling and interpretation of the spectral changes that occurred
      during the time course of the moisture sorption profile.

PMID- 16882460
TI  - Epidemiology--the leading health discipline.

PMID- 16882459
TI  - Potency assays for therapeutic live whole cell cancer vaccines.
AB  - Therapeutic cancer vaccines are under development with the goal of enhancing the
      body's immune response to cancer cells sufficient to arrest cancer cell growth.
      Among the various approaches being used are those based on whole tumor cells.
      Developing a suitable measure of the potency of such vaccines presents a
      significant challenge because neither cellular associated markers nor in vivo
      biological responses that are correlated with efficacy have been identified;
      nevertheless, manufacturers and regulatory agencies will need to develop methods
      to evaluate these products. At this moment, the challenge for manufacturers who
      are developing whole cell vaccines is to demonstrate batch-to-batch consistency
      for the vaccine used in clinical studies and to show that comparable vaccine
      batches have the same capacity to achieve an acceptable level of biological
      activity that may be related to efficacy. This is particularly challenging in
      that animal models to test that activity do not exist and direct serological or
      immunological correlates of clinical protection are not available because
      protection has not yet been established in clinical trials. In the absence of
      well-defined biological markers and tests for manufacturing consistency,
      manufacturers and regulators will need to rely heavily on a highly reproducible
      manufacturing process--the consistency of the process therefore becomes critical.
      In developing regulatory approaches to whole cell cancer vaccines, the experience
      from the field of infectious disease vaccines should be examined for general
      guidance. A framework that draws heavily on the field of infectious disease
      vaccines is presented and suggests that at this point in the development of this
      new class of products, it is reasonable to develop data on quantitative antigen
      expression as a measure of potency with the expectation that when clinical
      efficacy has been established it will confirm the appropriateness of this
      approach. But because this will not be known until the end of a pivotal trial, a
      bioassay should be considered and run in parallel. Several examples of bioassays
      are presented along with their advantages and disadvantages. The final selection
      of a potency assay for use in lot release of a commercializable therapeutic whole
      cell vaccine ultimately will depend on the totality of the data available at the
      time of approval by regulatory agencies. Based on information currently
      available, it is likely that quantitative antigen expression or a bioassay could
      be used to measure potency. If both are determined to be acceptable, the use of
      quantitative antigen expression could be considered for routine lot release,
      while the bioassay could be reserved for use as one of the elements in
      establishing comparability when manufacturing changes are being considered after
      approval.

PMID- 16882461
TI  - Relative weight and mobility: a longitudinal study in a biracial population of
      older adults.
AB  - PURPOSE: We examined the association of relative weight with mobility and changes
      in mobility over time and whether these associations differed by race. METHODS:
      Data come from a prospective, population-based, observational study of adults
      aged 65 years or older. Mobility outcomes were assessed at baseline and two
      follow-up interviews at 3-year intervals. The study included 4195 participants
      with a mean age of 73.8 +/- 6.3 (SD) years; 61.4% were women, and 60.9% were
      black. Assessment of mobility included a brief self-report instrument and a
      performance-based walk test. Body mass index (BMI, kilograms per square meter)
      was used as a measure of relative weight. We used generalized estimating equation
      models to examine change in mobility outcomes over time as a function of BMI.
      RESULTS: Average BMI was 26.6 +/- 5.7 kg/m(2), with 34.0% overweight and 23.4%
      obese. BMI showed a significant curvilinear association with mobility outcomes at
      baseline (p < 0.001), but was not associated with change in mobility during
      follow-up. Maximum mobility levels occurred at a significantly higher level of
      BMI among blacks than whites. CONCLUSIONS: Higher levels of BMI may lead to
      mobility impairments earlier in life, but there is little evidence that they
      increase the rate of decline in mobility in older age itself.

PMID- 16882462
TI  - Apolipoprotein E genotype and gallbladder disease risk in a large population
      based cohort.
AB  - PURPOSE: The aim of the study is to describe the association between
      apolipoprotein E (apoE) genotype and gallbladder disease incidence. METHODS:
      Cases of incident hospitalized gallbladder disease were ascertained in nearly
      13,000 middle-aged men and women participating in the Atherosclerosis Risk in
      Communities (ARIC) Study, a prospective cohort study in four US communities.
      RESULTS: Between the ARIC baseline examination (1987 to 1989) and December 31,
      2001, a total of 639 participants were hospitalized for gallbladder disease.
      After adjustment for age, sex, race, obesity, plasma lipid level, and diabetes,
      the relative risk for hospitalized gallbladder disease associated with the
      presence of an epsilon4 allele (i.e., genotypes E4/4, E3/4, and E2/4 versus other
      genotypes) was 0.72 (95% confidence interval [CI], 0.60-0.87). Stratification by
      race showed that the inverse association with epsilon4 was stronger in whites
      (relative risk, 0.69; 95% CI, 0.56-0.85) than African Americans (relative risk,
      0.86; 95% CI, 0.58-1.30). The presence of the other rare isoform, epsilon2 (i.e.,
      genotypes E2/2, E2/3, and E2/4 versus others) was associated with a modest
      increased risk for gallbladder disease (relative risk, 1.28; 95% CI, 1.05-1.57).
      CONCLUSIONS: These results suggest that independent of traditional risk factors,
      apoE genotype may influence gallbladder disease risk, particularly in whites. The
      exact biologic mechanism for such an association remains unclear and requires
      further investigation.

PMID- 16882464
TI  - Agreement between contemporaneously recorded and subsequently recalled time spent
      outdoors: implications for environmental exposure studies.
AB  - PURPOSE: The aim of the study is to evaluate the agreement between
      contemporaneously recorded and subsequently recalled time spent outdoors during 1
      week among members of an occupational cohort. METHODS: One hundred twenty-five
      radiologic technologists from northern and southern geographic areas in the
      United States recorded time spent outdoors for 7 consecutive days in a daily
      diary. Six months later, study participants completed a mailed self-administered
      questionnaire of the number of outdoor hours during the same 7-day period. We
      tested the agreement between questionnaire responses and diary entries. Logistic
      regression models were used to identify variables significantly affecting
      agreement. RESULTS: Time spent outdoors comprised one fifth of the total time
      recorded in the diaries. Agreement (weighted kappa [kappa(w)]) between reported
      outdoor time during weekdays (kappa(w) = 0.49; 95% confidence interval [CI], 0.39
      0.59) was significantly (p < 0.05) higher than for weekends (kappa(w) = 0.23; 95%
      CI, 0.12-0.34). Similarly, agreement was lower for weekends compared with
      weekdays in multivariate analyses, reaching statistical significance (p = 0.05)
      in only the southern regions. CONCLUSIONS: Although our investigation was carried
      out among volunteers from the US radiologic technologist cohort, we believe
      retrospective questionnaires may be more accurate in reporting time spent
      outdoors for weekdays compared with weekends in any group of indoor workers.
      These differences have implications for the wording in future questionnaires
      about time spent outdoors and level and sources of uncertainty characterizing
      estimated time spent outdoors on weekdays versus weekend days.

PMID- 16882463
TI  - Maternal hormone levels and perinatal characteristics: implications for
      testicular cancer.
AB  - PURPOSE: It was hypothesized that the risk for testicular germ cell tumors
      (TGCTs) is associated with maternal hormone levels. To examine the hypothesis,
      some studies used perinatal factors as surrogates for hormone levels. To
      determine the validity of this assumption, hormone-perinatal factor relationships
      were examined in the Collaborative Perinatal Project. METHODS: Maternal
      estradiol, estriol, and testosterone levels in first- and third-trimester serum
      samples were correlated with perinatal factors in 300 mothers representative of
      populations at high (white Americans) or low (black Americans) risk for TGCT.
      RESULTS: For white participants, testosterone levels were associated negatively
      with maternal height (p < 0.01) and age (p = 0.02) and positively with maternal
      weight (p = 0.02) and body mass index (BMI; p < 0.01), whereas estradiol levels
      were associated negatively with height (p = 0.03) and positively with son's birth
      weight (p = 0.04). For black participants, estriol levels were associated
      negatively with maternal weight (p = 0.01), BMI (p = 0.02), and gestational age p
      < 0.01) and positively with son's birth weight (p < 0.01), length (p = 0.04), and
      head circumference (p = 0.03). CONCLUSIONS: These findings indicate that use of
      perinatal characteristics as surrogates for hormone levels should be limited to a
      specific ethnic group. For white men, previously reported associations of TGCT
      with maternal weight and age may be caused by lower maternal testosterone levels.

PMID- 16882465
TI  - Body mass index and coronary heart disease risk score: the Tromso study, 1979 to
      2001.
AB  - PURPOSE: The purpose of the study is to examine the association between
      longitudinal change in body mass index (BMI) and change in coronary heart disease
      (CHD) risk score by using the Framingham risk score equation. METHODS: A general
      adult population in the municipality of Tromso, Norway, was invited to four
      consecutive examinations in 1979 to 1980, 1986 to 1987, 1994 to 1995, and 2001. A
      total of 10,214 men and women aged 20 to 61 years at baseline attended at least
      three times. Associations were examined by using fixed-effects regression methods
      for longitudinal data. RESULTS: We observed a significant association between BMI
      change and risk score change in all baseline age groups. The association was
      significantly strengthened by age in women, but not men. A BMI increase of 3
      kg/m(2) in subjects aged 40 to 49 years was associated with risk score increases
      of 0.45 points (95% confidence interval [CI], 0.29-0.62) in men and 0.66 points
      (95% CI, 0.52-0.80) in women. CONCLUSIONS: The well-known increase in body weight
      is associated with adverse CHD risk in both men and women.

PMID- 16882466
TI  - Modeling a syphilis outbreak through space and time using the Bayesian maximum
      entropy approach.
AB  - PURPOSE: The aim of the study is to describe changes in the spatial distribution
      of syphilis before, during, and after an outbreak in Baltimore, MD, by using
      Bayesian maximum entropy (BME), a modern geostatistical technique for space-time
      analysis and mapping. METHODS: BME was used to conduct simple and composite space
      time analyses of the density of syphilis infection based on primary, secondary
      and early latent syphilis cases reported to the Baltimore City Health Department
      between January 1, 1994, and December 31, 2002. RESULTS: Spatiotemporal
      covariance plots indicated that the distribution of the density of syphilis cases
      showed both spatial and temporal dependence. Temporally dependent disease maps
      suggested that syphilis increased within two geographic core areas of infection
      and spread outward. A new core area of infection was established to the
      northwest. As the outbreak waned, density diminished and receded in all core
      areas. Morbidity remained elevated in the two original central and new
      northwestern core areas after the outbreak. CONCLUSIONS: Density of syphilis
      infection was a simple informative measure easily compared across years. The BME
      approach was useful for quantitatively and qualitatively describing the spatial
      development and spread of syphilis. Our results are specific to Baltimore;
      however, the BME approach is generalizable to other settings and diseases.

PMID- 16882467
TI  - What are the costs of suspected but not reported tuberculosis?
AB  - PURPOSE: Little is known regarding patients suspected, but not proven, to have
      tuberculosis before meeting reporting requirements. These patients generate
      unmeasured tuberculosis costs to the health care system. Elimination efforts are
      undervalued without fully quantifying the burden of tuberculosis. This may lead
      to decreased support and resurgence of this disease. This report provides a
      preliminary quantification of these costs. METHODS: We used acid-fast bacillus
      (AFB) cultures completed as a proxy to estimate the number of patients with
      suspected tuberculosis who are never reported. We collected data on the number of
      AFB tests conducted in Tarrant County, TX, for calendar year 2002. We excluded
      all tests positive for Mycobacterium tuberculosis or secondary to growth of
      mycobacteria not M tuberculosis. We considered all AFBs conducted on an
      individual within 90 days to be single diagnostic episodes. We measured the
      number of diagnostic episodes, number of AFBs, number of AFBs meeting inclusion
      criteria, estimated cost incurred by testing, and individuals affected. RESULTS:
      The Tarrant County hospitals sampled completed 6935 AFB cultures on an inpatient
      volume of 142,356 patients. One hundred ninety-three cultures confirmed
      tuberculosis or other mycobacteria, and 6742 AFBs were collected on persons
      suspected, but not proved, to have tuberculosis at an estimated $114.06 per
      culture. The total cost of eliminating tuberculosis as a cause of illness was
      $768,993. Laboratory costs for each patient with suspected, but not confirmed,
      tuberculosis averaged $364.11. One hundred forty-eight AFB cultures costing
      $16,830 were needed to confirm one case of tuberculosis. CONCLUSIONS: The
      suspicion of tuberculosis incurs significant burdens and cost in the US health
      care system. More fully valuing tuberculosis elimination is important for
      tuberculosis management and will help maintain support for tuberculosis
      elimination.

PMID- 16882468
TI  - The importance of estimating selection bias on prevalence estimates shortly after
      a disaster.
AB  - PURPOSE: The aim was to study selective participation and its effect on
      prevalence estimates in a health survey of affected residents 3 weeks after a man
      made disaster in The Netherlands (May 13, 2000). METHODS: All affected adult
      residents were invited to participate. Survey (questionnaire) data were combined
      with electronic medical records of residents' general practitioners (GPs). Data
      for demographics, relocation, utilization, and morbidity 1 year predisaster and 1
      year postdisaster were used. RESULTS: The survey participation rate was 26% (N =
      1171). Women (odds ratio [OR], 1.46; 95% confidence interval [CI], 1.28-1.67),
      those living with a partner (OR, 2.00; 95% CI, 1.72-2.33), those aged 45 to 64
      years (OR, 2.00; 95% CI, 1.59-2.52), and immigrants (OR, 1.50; 95% CI, 1.30-1.74)
      were more likely to participate. Participation rate was not affected by
      relocation because of the disaster. Participants in the survey consulted their
      GPs for health problems in the year before and after the disaster more often than
      nonparticipants. Although there was selective participation, multiple imputation
      barely affected prevalence estimates of health problems in the survey 3 weeks
      postdisaster. CONCLUSIONS: Estimating actual selection bias in disaster studies
      gives better information about the study representativeness. This is important
      for policy making and providing effective health care.

PMID- 16882470
TI  - Specificity in dietary population research.

PMID- 16882471
TI  - Validity of self-reported menstrual cycle length.
AB  - PURPOSE: Self-reported menstrual cycle length has been associated with host and
      environmental factors and chronic disease risk. The purpose of this study is to
      evaluate the validity of self-reported cycle length. METHODS: The authors
      assessed the agreement between a woman's self-reported "usual" cycle length at
      study onset with the mean of her observed cycle lengths from prospective daily
      diaries for 398 women aged 19 to 41 years in the Mount Sinai Study of Women
      Office Workers (1990 to 1994). RESULTS: Forty-three percent of women self
      reported usual cycle lengths more than 2 days different from their mean length.
      When self-reported cycle length was categorized (<26, 26 to 35, and >35 days) and
      compared with mean cycle length, 21% of women were misclassified. Women who were
      older, married, and with higher income were more likely to have accurately
      reported their menstrual cycle length. Women who had short or long mean cycle
      lengths (lowest and highest quintile of length) were less likely to self-report
      accurately, and accuracy decreased monotonically with increasing cycle
      variability. CONCLUSIONS: These findings show considerable measurement error in
      self-reported cycle length, as well as describe population subgroups that report
      menstrual cycle length with the greatest accuracy.

PMID- 16882472
TI  - Regarding "Associations between socioeconomic status and cancer survival".

PMID- 16882473
TI  - Bowel movement, state of stool, and subsequent risk for colorectal cancer: the
      Japan public health center-based prospective study.
AB  - PURPOSE: Evidence about whether irregular bowel movements or unusual stool
      conditions are associated with colorectal cancer is still inconsistent. METHODS:
      We identified 479 newly diagnosed cases of colorectal cancer (303 men and 176
      women) during a 7.9-year follow-up of a cohort consisting of 57,940 subjects
      (27,529 men and 30,411 women) aged 40 to 69 years at baseline. Bowel movements
      and stool conditions were asked through a self-administered questionnaire.
      RESULTS: Neither high nor low frequency of bowel movements was associated with
      colorectal cancer incidence compared with one bowel movement per day.
      Multivariate hazard ratios (HRs) and 95% confidence intervals (CIs) for two bowel
      movements or more per day were 1.03 (95% CI, 0.76-1.41) in men and 1.16 (95% CI,
      0.68-2.00) in women. HRs for two to three bowel movements per week were 0.97 (95%
      CI, 0.61-1.55) in men and 0.75 (95% CI, 0.49-1.13) in women. There was no clear
      association between an unusual stool state, such as diarrhea or hard stools, and
      colorectal cancer. CONCLUSION: Our results suggest that neither bowel movement
      frequency nor any specific state of stool causes colorectal cancer.

PMID- 16882474
TI  - Regarding "prevalence of the metabolic syndrome in relation to self-reported
      cancer history".

PMID- 16882476
TI  - Principles of antimicrobial therapy: what should we be using?
AB  - Although the use of antimicrobials has had an insurmountable impact on preventing
      patient morbidity and mortality, problems with antimicrobial resistance and
      antimicrobial-induced diarrhea are becoming more apparent in human and veterinary
      medicine. The mortality associated with nosocomial infection with antimicrobial
      resistant bacteria in human patients is alarming. Similarly, in veterinary
      medicine, the morbidity and high cost of treatment of patients with postoperative
      infection, for example, are concerns. Specifically in equine medicine, the high
      morbidity and mortality associated with antimicrobial-induced diarrhea have been
      devastating in many equine practices. Misuse of antimicrobials is extremely
      common in human and veterinary medicine. All clinicians have the responsibility
      to consider the appropriateness of their antimicrobial use carefully and,
      whenever possible, to minimize antimicrobial administration to patients.

PMID- 16882477
TI  - New antimicrobials, systemic distribution, and local methods of antimicrobial
      delivery in horses.
AB  - The local delivery of antimicrobials is a valuable therapeutic tool with a low
      morbidity, is practical to use, and is well tolerated by horses. Clinically, its
      use has allowed equine practitioners to achieve better results when treating
      musculoskeletal infections, and it represents an extremely useful tool in the
      practitioner's armamentarium against these types of infections. The technique is
      indicated to combat orthopedic infections involving bones, joints, physes, tendon
      sheaths, and foot tissues. Optimal treatment must include other approaches, such
      as systemic antimicrobial therapy and surgical debridement and lavage, and
      monitoring of the clinical progression of the patient can help to determine the
      ideal protocol for each patient.

PMID- 16882478
TI  - Prevention of postoperative infections in horses.
AB  - The best defense against postoperative infection is to use multiple strategies to
      minimize wound contamination, maintain wound tissue health, and provide rational
      antimicrobial strategies that do not promote the development of resistant
      bacteria and superinfections.

PMID- 16882479
TI  - Surgical and traumatic wound infections, cellulitis, and myositis in horses.
AB  - Surgical site infections (SSIs) and traumatic wound management remain challenging
      clinical scenarios. The prevention of SSIs involves meticulous surgical technique
      and aftercare. Traumatic wounds require thorough evaluation to assess the
      involvement of synovial structures and radiographs to check for fractures.
      Chronic wounds can require a biopsy and histologic evaluation to obtain a
      diagnosis, because many underlying pathologic processes grossly appear similar
      but different treatment regimens are required. Early recognition and diagnosis of
      cellulitis and myositis enable the rapid aggressive intervention necessary for a
      positive outcome. Any delay in diagnosis and treatment increases the complication
      and mortality rates and makes these conditions difficult to treat successfully.

PMID- 16882480
TI  - Septic arthritis, tenosynovitis, and infections of hoof structures.
AB  - Infectious diseases of synovial and hoof structures in horses can be devastating
      to soundness and can result in life-threatening complications. Timely diagnosis
      and early aggressive treatment can result in successful outcomes and resumption
      of athletic careers; however, delays in recognition and therapy can be the most
      costly reasons for failure. Sterilization of affected compartments and tissues
      requires removal of microorganisms and compromised tissue. Debridement, lavage,
      and appropriate antimicrobial drug use are the most reliable avenues of
      treatment. Antimicrobial drugs can be administered by local, regional, and
      systemic routes. Lavage techniques and debridement typically require surgical
      manipulations.

PMID- 16882481
TI  - Osteomyelitis in horses.
AB  - Much has been learned in the past decade about osteomyelitis. The inhibitory
      mechanisms of the "biofilm slime" layer that is formed by bacterial extracapsular
      exopolysaccharides and binds to bone, joints, and implants are now better
      understood than in the past. The surface colonization of bacteria that occurs
      within these biofilms is a biologic phenomenon that is somewhat unique to
      orthopedic infections. This survival strategy of bacteria is effective, and it is
      important for veterinarians who treat osteomyelitis to be aware of current
      diagnostic and therapeutic treatment modalities. The practitioner should be aware
      of the most common bacteria associated with osteomyelitis and the traditional
      treatments that are still used. Current therapeutic treatment modalities, such as
      antibiotic- impregnated polymethylmethacrylate, antibiotic-impregnated plaster of
      Paris, and regional perfusion, have become routine, however, and have been
      responsible for improving the prevention and outcome of osteomyelitis in the
      horse. It is the intent of this article to make equine veterinarians aware of
      current information as well as the future treatments of osteomyelitis.

PMID- 16882482
TI  - Infections in the equine abdomen and pelvis: perirectal abscesses, umbilical
      infections, and peritonitis.
AB  - This article addresses the pathophysiology, diagnosis, management, and prognosis
      of several different infections within the equine abdomen and pelvic region. The
      latest advances in the diagnosis and treatment of perirectal abscesses, umbilical
      infections, and local and diffuse peritonitis are discussed. Emphasis is placed
      on recent advances in diagnostics and therapeutics with reference to human
      literature that may be useful in equine practice.

PMID- 16882483
TI  - Enteritis and colitis in horses.
AB  - Enteritis and colitis remain challenging and life-threatening diseases despite
      many recent advances. Successful treatment is largely dependent on early
      recognition and directed therapy, which is facilitated by obtaining a complete
      history and physical examination. A number of new therapies and methods of
      monitoring critically ill patients have become integral components of treatment
      success. The critical monitoring of equine foals and adults continues to be an
      exciting and emerging field.

PMID- 16882484
TI  - Septicemia and cardiovascular infections in horses.
AB  - This article first reviews cardiovascular infections, including endocarditis,
      myocarditis, vasculitis, and pericarditis. It then addresses what is known at
      this stage about the effects of sepsis on the cardiovascular system. Some
      information is provided from current human literature to familiarize the reader
      with the diagnostics and therapeutics that may eventually be used in equine
      practice as well.

PMID- 16882485
TI  - Pathophysiology, diagnosis, and management of urinary tract infection in horses.
AB  - Equine urinary tract infection (UTI) most commonly occurs as a sequela to
      structural or functional inhibition of normal urine flow. Although it is an
      infrequent diagnosis in equids, the incidence of UTI in human beings is high and
      has inspired great investigative effort. The resultant findings with potentially
      broad application as well as current equine studies are reviewed here. Recent
      developments in the understanding of host-agent interactions and renal defense
      mechanisms, emerging antimicrobial resistance, and novel therapeutic alternatives
      to prophylactic antibiotic use are emphasized.

PMID- 16882487
TI  - Meningitis and encephalomyelitis in horses.
AB  - This article provides an overview of meningitis and encephalomyelitis in horses,
      including diagnostic tests, treatment developments, and preventative measures
      reported in the equine and human medical literature of the past few years.

PMID- 16882486
TI  - Reproductive tract infections in horses.
AB  - Diagnosis, treatment, and, ultimately, prevention of reproductive disease are
      vital components of equine veterinary medicine. A thorough understanding of
      anatomy and physiology is necessary to reconcile the pathologic findings of
      disease. Only then can a rational treatment plan be formulated. Many recent
      advances in knowledge about the reproductive system of multiple species have
      application to the mare and stallion.

PMID- 16882488
TI  - Infections of the head and ocular structures in the horse.
AB  - Infectious conditions of the equine head are commonly encountered in clinical
      practice. Pathogenic bacterial, viral, and fungal organisms may localize in the
      extensive nasal passages, paranasal sinuses, and guttural pouches, creating a
      range of clinical signs and conditions that can be severe enough to lead to
      unexpected fatality. Renewed interest in equine dentistry has led to a greater
      recognition of dental disease that is associated with infection. This article
      focuses on bacterial and fungal infections of the main anatomic regions of the
      equine head, where advances in diagnosis and management have been made or
      consolidated in recent years. It also addresses recent advances made in the area
      of infectious equine corneal disease, including bacterial, viral, and fungal
      etiologies. Recent developments in equine recurrent uveitis as it relates to
      infectious diseases and ocular manifestations of systemic disease are also
      discussed.

PMID- 16882489
TI  - Advanced techniques in the diagnosis and management of infectious pulmonary
      diseases in horses.
AB  - Techniques for novel approaches to the diagnosis and management of equine
      pulmonary disease continue to be developed and used in clinical practice.
      Diagnostic techniques involving immunoassays and nucleic acid-based tests not
      only decrease the time in which results become available but increase the
      sensitivity and specificity of test results. These assays do not substitute for
      careful clinical evaluation but can shorten the time to a confirmed accurate
      diagnosis, and thus allow for early initiation of therapeutic strategies and
      prevention protocols. With further understanding of the molecular biology and
      immunology of equine pulmonary disease, diagnostic and management techniques
      should become further refined.

PMID- 16882492
TI  - Carcinoid tumors.
AB  - Carcinoid tumors can present a difficult diagnostic and therapeutic dilemma.
      Despite their reputation as indolent tumors, they frequently metastasize and can
      cause significant symptomatology. The only curative therapy remains surgical
      resection. The prognosis and treatment of carcinoids vary based on location and
      histology, and therapy must be tailored to each patient.

PMID- 16882493
TI  - Gastrinoma: sporadic and familial disease.
AB  - The physiologic sequelae of a gastrinoma can be well controlled with medical
      therapy. The role of surgery has shifted from managing acid hyper-secretion and
      ulcer complications to preventing metastatic disease and managing symptomatic
      metastases. With improved methods of imaging for the detection of occult
      gastrinomas, the prospective evaluation of the role for surgery in altering the
      natural history of these tumors is now possible.

PMID- 16882494
TI  - Neuroendocrine tumors of the pancreas, excluding gastrinoma.
AB  - In summary, neuroendocrine tumors of the pancreas comprise a unique and
      relatively rare group of tumors, of which gastrinoma and insulinoma are the most
      common types. Insulinomas tend to be small, solitary and benign, with surgical
      resection curable in most cases. The remainder of the neuroendocrine tumors are
      usually large, and unlikely to be cured with surgery; their slow-growing nature,
      however, mandates aggressive surgical therapy; even in cases where metastatic
      disease is present. Somatostatin analogs such as octreotide, are used to control
      the symptoms of hormone secretion; they are generally less effective in patients
      with insulinoma than in those with the other neuroendocrine tumors. Streptozocin,
      5-fluorouracil, and doxorubicin are the most widely used chemotherapeutic agents
      in metastatic neuroendocrine tumors; their efficacy is limited, and significant
      side effects limit their use. Finally, liver transplantation in very select
      patients may prolong survival and alleviate debilitating symptoms.

PMID- 16882495
TI  - Treatment of metastatic disease in patients with neuroendocrine tumors.
AB  - Gastroenteropancreatic neuroendocrine tumors (GENTs) compromise a heterogeneous
      group of relatively uncommon neoplasms with a yearly incidence rate of 1.2 to 3.0
      per 100,000 population. These tumors share numerous histologic and biologic
      features, allowing their consideration as a common entity. They are postulated to
      arise from neuroendocrine cells, but most are not from neural crest origin. Their
      predominant site of origin is the gastrointestinal tract, where most involve the
      small intestine and appendix, but are also found in the adrenal medulla,
      bronchopulmonary system, pancreas, thyroid, parathyroid, and paraganglia cells. A
      common feature is their often indolent course, but some tumors are poorly
      differentiated and behave aggressively. This article addresses the surgical
      management of endocrine malignancies and the treatment of metastatic disease in
      patients with neuroendocrine tumors.

PMID- 16882496
TI  - Adrenocortical carcinoma.
AB  - ACC is a rare clinical entity that carries a poor prognosis; early diagnosis and
      complete surgical resection are associated with the improvement in patient
      survival. Even with appropriated diagnosis and treatment, most patients will
      develop recurrence and succumb to ACC because of the underlying tumor biology,
      the difficulty of achieving a complete resection, and the lack of effective
      systemic therapies. Despite its many drawbacks, mitotane continues to be a
      mainstay in the treatment of high-risk patients with ACC, especially those with
      recurrent or metastatic disease. Recent findings suggest that mitotane, combined
      with conventional chemotherapeutic agents, may improve survival for such
      patients.

PMID- 16882497
TI  - Malignant pheochromocytoma.
AB  - Malignant pheochromocytoma is a rare disease with a high mortality. Surgical
      resection is the only effective treatment if extensive metastatic disease is not
      present. However, differentiating between benign and malignant pheochromocytoma
      is impossible in the absence of locoregional invasion or distant metastasis. This
      diagnostic dilemma has several drawbacks, including later detection and treatment
      of recurrence than if malignancy is determined at the original operation. With
      emerging molecular markers of malignant disease, optimal extent and approach for
      surgical treatment and appropriate extent of follow up could be established based
      on specific tumor behavior and the need for additional systemic therapy.

PMID- 16882498
TI  - Parathyroid cancer.
AB  - Parathyroid cancer is a rare endocrine tumor and an uncommon cause of HPT.
      Advances have been made to identify a promising molecular diagnostic marker for
      the disease. The use of accurate preoperative imaging modalities would
      undoubtedly facilitate its management by making an accurate preoperative
      diagnosis by assessing its invasiveness, and by searching for nodal or distant
      metastases. The effectiveness of the application of intraoperative PTH assay in
      the management of this rare condition remains to be seen. Radical surgical
      treatment offers the best chance of cure, but for patients who have refractory
      unresectable disease or metastases, the availability of more effective targeted
      medical therapy may palliate the debilitating symptoms of hypercalcemia, reduce
      its metabolic complications, and potentially improve survival.

PMID- 16882499
TI  - Papillary thyroid cancer.
AB  - In summary, PTC is common, although it rarely results in disease-specific
      mortality. It is being diagnosed increasingly in the subclinical phase as a
      result of enhanced ultrasound imaging and more aggressive surveillance of smaller
      thyroid nodules. US-guided FNA is the "gold-standard" for diagnosis. Although
      controversy continues about the appropriate surgical management of PTC, total
      thyroidectomy is usually indicated given the frequent multicentricity and
      metastases of the disease, which in turn, necessitates adjuvant RAI and careful
      surveillance. An enhanced prognostic classification could better guide initial
      surgical therapy, standardize surveillance, and reduce the risk of recurrent and
      persistent disease. Research efforts should focus on the genetic and molecular
      underpinnings of PTC, as these would facilitate the identification of additional
      prognostic factors and potential targets for novel therapies.

PMID- 16882500
TI  - Follicular and Hurthle cell carcinoma of the thyroid gland.
AB  - Follicular and Hurthle cell carcinoma of the thyroid gland are uncommon tumors
      that are genotypically similar. Current and future diagnostic adjuncts,
      treatment, and postoperative follow-up for patients with follicular and Hurthle
      cell cancer are outlined. Risk factors for recurrence and mortality and the
      reported outcomes of treatment of follicular and Hurthle cell carcinoma are
      reviewed.

PMID- 16882501
TI  - The role of radioactive iodine in the treatment of well-differentiated thyroid
      cancer.
AB  - The prognosis in differentiated thyroid cancer is excellent. The completeness of
      thyroidectomy and removal of involved regional metastases are the most important
      elements of management. Iodine 131 has a role in ablating residual thyroid and
      treating regional and distant metastases. The effectiveness of the treatment is
      confirmed by negative follow-up scans and low or undetectable Tg. This therapy is
      relatively specific, but other tissues can receive meaningful doses of radiation
      and acute and long-term complications can occur. Therefore, whether the patient
      will have a better prognosis after treatment with 131I and whether the benefits
      of treatment are greater than the side effects must be determined for every
      patient.

PMID- 16882502
TI  - Medullary thyroid cancer.
AB  - The goal in managing patients who have MTC is to detect and surgically remove
      disease at an early stage. Tumor marker-based biochemical screening and DNA-based
      genetic screening have created the opportunity for effective prophylactic surgery
      in patients at risk for hereditary MTC. Complete surgical resection is critical
      for cure because cervical reoperation for persistent or recurrent disease
      benefits only select patients. With the advent of therapies that target the RET
      activated pathways, new hope may be emerging for patients who have locally
      advanced or metastatic disease.

PMID- 16882504
TI  - The ICMCC second conference on "Medical and Care Compunetics".

PMID- 16882503
TI  - Anaplastic thyroid carcinoma, thyroid lymphoma, and metastasis to thyroid.
AB  - Anaplastic thyroid carcinoma, thyroid lymphoma, and secondary metastasis to the
      thyroid gland are uncommon thyroid malignancies. They represent significant
      challenges for the surgeon owing to difficulties in diagnosis, aggressive
      biology, and the infrequency of their presentation. An awareness and appreciation
      of multimodality treatment strategies is essential for their management.

PMID- 16882505
TI  - Global perspective on environmental health.

PMID- 16882507
TI  - Dietary nitrate: where is the risk?

PMID- 16882510
TI  - Crisis not over for hurricane victims.

PMID- 16882508
TI  - Manganese as a potential confounder of serum prolactin.

PMID- 16882511
TI  - The apple bites back: claiming old orchards for residential development.

PMID- 16882512
TI  - A risky environment for investment.

PMID- 16882513
TI  - Shiny science: a new substitute for hexavalent chromium.

PMID- 16882515
TI  - Evoecotoxicology: environmental changes and life features development during the
      evolutionary process-the record of the past at developmental stages of living
      organisms.
AB  - For most of evolutionary history, scientific understanding of the environment and
      life forms is extremely limited. In this commentary I discuss the hypothesis that
      ontogenetic features of living organisms can be considered biomarkers of
      coevolution between organisms and physicochemical agents during Earth's history.
      I provide a new vision of evolution based on correlations between metabolic
      features and stage-dependent susceptibility of organisms to physicochemical
      agents with well-known environmental signatures. Thus, developmental features
      potentially reflect environmental changes during evolution. From this
      perspective, early multicellular life forms would have flourished in the anoxic
      Earth more than 2 billion years ago, which is at least 1.2 billion years in
      advance of available fossil evidence. The remarkable transition to aerobic
      metabolism in gastrula-stage embryos potentially reflects evolution toward
      tridermic organisms by 2 billion years ago. Noteworthy changes in embryonic
      resistance to physicochemical agents at different developmental stages that can
      be observed in living organisms potentially reflect the influence of
      environmental stress conditions during different periods of evolutionary history.
      Evoecotoxicology, as a multidisciplinary and transdisciplinary approach, can
      enhance our understanding of evolution, including the phylogenetic significance
      of differences in susceptibility/resistance to physicochemical agents in
      different organisms.

PMID- 16882516
TI  - Biomonitoring and biomarkers: exposure assessment will never be the same.
AB  - Using modern analytical technology, it is now possible to measure almost any
      chemical present in our bodies. The future role of classical exposure assessment
      will perhaps be marginalized because biomonitoring programs can directly measure
      the concentration of chemicals that are present in biologic matrices. Although
      the concentration of chemicals in the environment will continue to be measured
      and related to exposure parameters, the prioritization of the national
      environmental agenda will be dictated by biomonitoring. Recent biomonitoring
      studies have examined the levels of >200 chemicals. Biomonitoring data, by
      themselves, are not informative in helping consumers understand their individual
      health risk. A major challenge facing those who conduct biomonitoring programs is
      how to best communicate the information to the public. In this article, we review
      benefits and challenges, along with select results from the Centers for Disease
      Control and Prevention's 2005 National Report on Human Exposure to Environmental
      Chemicals. We recommend that these data be carefully interpreted, with the goal
      of establishing baseline exposure information, rather than creating surrogates
      for conclusions about human health risk.

PMID- 16882517
TI  - The environmental "riskscape" and social inequality: implications for explaining
      maternal and child health disparities.
AB  - BACKGROUND: Research indicates that the double jeopardy of exposure to
      environmental hazards combined with place-based stressors is associated with
      maternal and child health (MCH) disparities. OBJECTIVE AND DISCUSSION: Our aim is
      to present evidence that individual-level and place-based psychosocial stressors
      may compromise host resistance such that environmental pollutants would have
      adverse health effects at relatively lower doses, thus partially explaining MCH
      disparities, particularly poor birth outcomes. Allostatic load may be a
      physiologic mechanism behind the moderation of the toxic effect of environmental
      pollutants by social stressors. We propose a conceptual framework for holistic
      approaches to future MCH research that elucidates the interplay of psychosocial
      stressors and environmental hazards in order to better explain drivers of MCH
      disparities. CONCLUSION: Given the complexity of the link between environmental
      factors and MCH disparities, a holistic approach to future MCH research that
      seeks to untangle the double jeopardy of chronic stressors and environmental
      hazard exposures could help elucidate how the interplay of these factors shapes
      persistent racial and economic disparities in MCH.

PMID- 16882519
TI  - Oxidative metabolites of diisononyl phthalate as biomarkers for human exposure
      assessment.
AB  - Diisononyl phthalate (DINP) is a complex mixture of predominantly nine-carbon
      branched-chain dialkyl phthalate isomers. Similar to di(2-ethylhexyl) phthalate,
      a widely used phthalate, DINP causes antiandrogenic effects on developing rodent
      male fetuses. Traditionally, assessment of human exposure to DINP has been done
      using monoisononyl phthalate (MINP) , the hydrolytic metabolite of DINP, as a
      biomarker. However, MINP is only a minor urinary metabolite of DINP. Oxidative
      metabolites, including mono(carboxyisooctyl) phthalate (MCIOP) ,
      mono(oxoisononyl) phthalate (MOINP) , and mono(hydroxyisononyl) phthalate (MHINP)
      are the major urinary metabolites in DINP-dosed rats. The urinary concentrations
      of MINP, MCIOP, MOINP, and MHINP were measured in 129 adult anonymous human
      volunteers with no known exposure to DINP. Although MINP was not present at
      detectable levels in any of the samples analyzed, MCIOP, MHINP, and MOINP were
      detected in 97, 100, and 87% of the urine samples at geometric mean levels equal
      to 8.6, 11.4, and 1.2 ng/mL, respectively. The concentrations of all three
      oxidative metabolites were highly correlated with each other (p<0.0001), which
      confirms a common precursor. MCIOP was excreted predominantly as a free species,
      whereas MOINP was excreted mostly in its glucuronidated form. The percentage of
      MHINP excreted either glucuronidated or in its free form was similar. The
      significantly higher frequency of detection and urinary concentrations of
      oxidative metabolites than of MINP suggest that these oxidative metabolites are
      better biomarkers of exposure assessment of DINP than is MINP. Therefore, we
      concluded that the prevalence of human exposure to DINP is underestimated by
      using MINP as the sole DINP urinary biomarker.

PMID- 16882518
TI  - Digestion assays in allergenicity assessment of transgenic proteins.
AB  - The food-allergy risk assessment for transgenic proteins expressed in crops is
      currently based on a weight-of-evidence approach that holistically considers
      multiple lines of evidence. This approach recognizes that no single test or
      property is known to distinguish allergens from nonallergens. The stability of a
      protein to digestion, as predicted by an in vitro simulated gastric fluid assay,
      currently is used as one element in the risk assessment process. A review of the
      literature on the use of the simulated gastric fluid assay to predict the
      allergenic status of proteins suggests that more extensive kinetic studies with
      well-characterized reference proteins are required before the predictive value of
      this assay can be adequately judged.

PMID- 16882520
TI  - Estimation of relative bioavailability of lead in soil and soil-like materials
      using young Swine.
AB  - In this article we summarize the results of a series of studies that measured the
      relative bioavailability (RBA) of lead in a variety of soil and soil-like test
      materials. Reference material (Pb acetate) or Pb-contaminated soils were
      administered orally to juvenile swine twice a day for 15 days. Blood samples were
      collected from each animal at multiple times during the course of the study, and
      samples of liver, kidney, and bone were collected at sacrifice. All samples were
      analyzed for Pb. We estimated the RBA of a test material by fitting mathematical
      models to the dose-response curves for each measurement end point and finding the
      ratio of doses that gave equal responses. The final RBA for a test material is
      the simple average of the four end point-specific RBA values. Results from 19
      different test materials reveal a wide range of RBA values across different
      exposure materials, ranging from 6 to 105%. This variability in RBA between
      different samples highlights the importance of reliable RBA data to help improve
      risk assessments for Pb in soil. Although the RBA value for a sample depends on
      the relative amounts of the different chemical and physical forms of Pb present,
      data are not yet adequate to allow reliable quantitative predictions of RBA from
      chemical speciation data alone.

PMID- 16882521
TI  - Translocation of inhaled ultrafine manganese oxide particles to the central
      nervous system.
AB  - BACKGROUND: Studies in monkeys with intranasally instilled gold ultrafine
      particles (UFPs; <100 nm) and in rats with inhaled carbon UFPs suggested that
      solid UFPs deposited in the nose travel along the olfactory nerve to the
      olfactory bulb. METHODS: To determine if olfactory translocation occurs for other
      solid metal UFPs and assess potential health effects, we exposed groups of rats
      to manganese (Mn) oxide UFPs (30 nm; approximately 500
      microg/m(superscript)3(/superscript)) with either both nostrils patent or the
      right nostril occluded. We analyzed Mn in lung, liver, olfactory bulb, and other
      brain regions, and we performed gene and protein analyses. RESULTS: After 12 days
      of exposure with both nostrils patent, Mn concentrations in the olfactory bulb
      increased 3.5-fold, whereas lung Mn concentrations doubled; there were also
      increases in striatum, frontal cortex, and cerebellum. Lung lavage analysis
      showed no indications of lung inflammation, whereas increases in olfactory bulb
      tumor necrosis factor-alpha mRNA (approximately 8-fold) and protein
      (approximately 30-fold) were found after 11 days of exposure and, to a lesser
      degree, in other brain regions with increased Mn levels. Macrophage inflammatory
      protein-2, glial fibrillary acidic protein, and neuronal cell adhesion molecule
      mRNA were also increased in olfactory bulb. With the right nostril occluded for a
      2-day exposure, Mn accumulated only in the left olfactory bulb. Solubilization of
      the Mn oxide UFPs was <1.5% per day. CONCLUSIONS: We conclude that the olfactory
      neuronal pathway is efficient for translocating inhaled Mn oxide as solid UFPs to
      the central nervous system and that this can result in inflammatory changes. We
      suggest that despite differences between human and rodent olfactory systems, this
      pathway is relevant in humans.

PMID- 16882522
TI  - Levels and concentration ratios of polychlorinated biphenyls and polybrominated
      diphenyl ethers in serum and breast milk in Japanese mothers.
AB  - Blood and/or breast milk have been used to assess human exposure to various
      environmental contaminants. Few studies have been available to compare the
      concentrations in one matrix with those in another. The goals of this study were
      to determine the current levels of polybrominated diphenyl ethers (PBDEs) and
      polychlorinated biphenyls (PCBs) in Japanese women, with analysis of the effects
      of lifestyle and dietary habits on these levels, and to develop a quantitative
      structure-activity relationship (QSAR) with which to predict the ratio of serum
      concentration to breast milk concentration. We measured PBDEs and PCBs in 89
      paired samples of serum and breast milk collected in four regions of Japan in
      2005. The geometric means of the total concentrations of PBDE (13 congeners) in
      milk and serum were 1.56 and 2.89 ng/g lipid, respectively, whereas those of
      total PCBs (15 congeners) were 63.9 and 37.5 ng/g lipid, respectively. The major
      determinant of total PBDE concentration in serum and milk was the geographic area
      within Japan, whereas nursing duration was the major determinant of PCB
      concentration. BDE-209 was the most predominant PBDE congener in serum but not in
      milk. The excretion of BDE 209 in milk was lower than that of BDE 47 and BDE 153.
      QSAR analysis revealed that two parameters, calculated octanol/water partition
      and number of hydrogen-bond acceptors, were significant descriptors. During the
      first weeks of lactation, the predicted partitioning of PBDE and PCB congeners
      from serum to milk agreed with the observed values. However, the prediction
      became weaker after 10 weeks of nursing.

PMID- 16882524
TI  - Arsenic exposure is associated with decreased DNA repair in vitro and in
      individuals exposed to drinking water arsenic.
AB  - The mechanism(s) by which arsenic exposure contributes to human cancer risk is
      unknown ; however, several indirect cocarcinogenesis mechanisms have been
      proposed. Many studies support the role of As in altering one or more DNA repair
      processes. In the present study we used individual-level exposure data and
      biologic samples to investigate the effects of As exposure on nucleotide excision
      repair in two study populations, focusing on the excision repair cross-complement
      1 (ERCC1) component. We measured drinking water, urinary, or toenail As levels
      and obtained cryopreserved lymphocytes of a subset of individuals enrolled in
      epidemiologic studies in New Hampshire (USA) and Sonora (Mexico). Additionally,
      in corroborative laboratory studies, we examined the effects of As on DNA repair
      in a cultured human cell model. Arsenic exposure was associated with decreased
      expression of ERCC1 in isolated lymphocytes at the mRNA and protein levels. In
      addition, lymphocytes from As-exposed individuals showed higher levels of DNA
      damage, as measured by a comet assay, both at baseline and after a 2
      acetoxyacetylaminofluorene (2-AAAF) challenge. In support of the in vivo data, As
      exposure decreased ERCC1 mRNA expression and enhanced levels of DNA damage after
      a 2-AAAF challenge in cell culture. These data provide further evidence to
      support the ability of As to inhibit the DNA repair machinery, which is likely to
      enhance the genotoxicity and mutagenicity of other directly genotoxic compounds,
      as part of a cocarcinogenic mechanism of action.

PMID- 16882525
TI  - Inferences drawn from a risk assessment compared directly with a randomized trial
      of a home drinking water intervention.
AB  - Risk assessments and intervention trials have been used by the U.S. Environmental
      Protection Agency to estimate drinking water health risks. Seldom are both
      methods used concurrently. Between 2001 and 2003, illness data from a trial were
      collected simultaneously with exposure data, providing a unique opportunity to
      compare direct risk estimates of waterborne disease from the intervention trial
      with indirect estimates from a risk assessment. Comparing the group with water
      treatment (active) with that without water treatment (sham), the estimated annual
      attributable disease rate (cases per 10,000 persons per year) from the trial
      provided no evidence of a significantly elevated drinking water risk
      [attributable risk=-365 cases/year, sham minus active; 95% confidence interval
      (CI) , -2,555 to 1,825]. The predicted mean rate of disease per 10,000 persons
      per person-year from the risk assessment was 13.9 (2.5, 97.5 percentiles: 1.6,
      37.7) assuming 4 log removal due to viral disinfection and 5.5 (2.5, 97.5
      percentiles: 1.4, 19.2) assuming 6 log removal. Risk assessments are important
      under conditions of low risk when estimates are difficult to attain from trials.
      In particular, this assessment pointed toward the importance of attaining site
      specific treatment data and the clear need for a better understanding of viral
      removal by disinfection. Trials provide direct risk estimates, and the upper
      confidence limit estimates, even if not statistically significant, are
      informative about possible upper estimates of likely risk. These differences
      suggest that conclusions about waterborne disease risk may be strengthened by the
      joint use of these two approaches. Key words: drinking water, gastrointestinal,
      intervention trial, microbial risk assessment, waterborne pathogens.

PMID- 16882523
TI  - Low blood lead levels do not appear to be further reduced by dietary supplements.
AB  - OBJECTIVE: Our objective was to evaluate the association of dietary intakes of
      selected micronutrients and blood lead (PbB) concentrations in female adults and
      in children. DESIGN: With longitudinal monitoring, we measured daily intakes of
      the micronutrients calcium, magnesium, sodium, potassium, barium, strontium,
      phosphorus, zinc, iron (limited data), and copper from 6-day duplicate diets (2
      13 collections per individual) and PbB concentrations. Participants were three
      groups of females of child-bearing age (one cohort consisting of 21 pregnant
      subjects and 15 nonpregnant controls, a second cohort of nine pregnant migrants),
      and one group of 10 children 6-11 years of age. RESULTS: Mean PbB concentrations
      were <5 microg/dL. A mixed linear model that included only group and time
      accounted for 5.9% of the variance of the PbB measurements; neither the effect of
      time nor the effect of group was significant. The model containing all of the
      micronutrients (except iron, for which there was a great deal of missing data),
      along with time and group, accounted for approximately 9.2% of the variance of
      PbB; this increase was not statistically significant. There was, however, a
      significant association of PbB with phosphorus, magnesium, and copper when all
      micronutrients were included in the statistical analysis, perhaps reflecting a
      synergistic effect. CONCLUSIONS: In contrast to most previous studies, we found
      no statistically significant relationships between the PbB concentrations and
      micronutrient intake. In adults and older children with low PbB concentrations
      and minimal exposure to Pb, micronutrient supplementation is probably
      unnecessary.

PMID- 16882526
TI  - Phorate exposure and incidence of cancer in the agricultural health study.
AB  - BACKGROUND: We recently reported a link between use of the organophosphate
      pesticide phorate and risk of prostate cancer among applicators with a family
      history of prostate cancer in the Agricultural Health Study (AHS). OBJECTIVE:
      This finding, together with findings of associations between other
      organophosphate pesticides and cancer more broadly, prompted us to examine
      phorate exposure and overall cancer incidence in the AHS. Adding 3 years of
      follow-up and using more detailed exposure information allowed us to see whether
      the prostate cancer finding held. METHODS: The AHS is a prospective study of
      licensed restricted-use pesticide applicators from North Carolina and Iowa. To
      our knowledge, this is the largest examination of workers occupationally exposed
      to phorate. Pesticide exposure and other information was collected using two self
      administered questionnaires completed from 1993 to 1997. Poisson regression was
      used to calculate rate ratios (RR) and 95% confidence intervals (CI), adjusting
      for potential confounders. RESULTS: Phorate use was not related to the incidence
      of all cancers combined or to any individual cancer, although we had insufficient
      numbers to study non-Hodgkin lymphoma or leukemia, which have been linked to
      organophosphates in other studies. Although prostate cancer risk was not
      significantly related to phorate use overall or among those without a family
      history, the risk tended to increase among applicators with a family history of
      prostate cancer. The interaction RR was 1.53 (95% CI, 0.99-2.37). CONCLUSION: The
      observed statistical interaction suggests a gene-environment interaction between
      family history and phorate exposure in the incidence of prostate cancer, but
      other explanations are also possible.

PMID- 16882527
TI  - Volatile organic compounds and pulmonary function in the Third National Health
      and Nutrition Examination Survey, 1988-1994.
AB  - BACKGROUND: Volatile organic compounds (VOCs) are present in much higher
      concentrations indoors, where people spend most of their time, than outdoors and
      may have adverse health effects. VOCs have been associated with respiratory
      symptoms, but few studies address objective respiratory end points such as
      pulmonary function. Blood levels of VOCs may be more indicative of personal
      exposures than are air concentrations; no studies have addressed their
      relationship with respiratory outcomes. OBJECTIVE: We examined whether
      concentrations of 11 VOCs that were commonly identified in blood from a sample of
      the U.S. population were associated with pulmonary function. METHODS: We used
      data from 953 adult participants (20-59 years of age) in the Third National
      Health and Nutrition Examination Survey (1988-1994) who had VOC blood measures as
      well as pulmonary function measures. Linear regression models were used to
      evaluate the relationship between 11 VOCs and measures of pulmonary function.
      RESULTS: After adjustment for smoking, only 1,4-dichlorobenzene (1,4-DCB) was
      associated with reduced pulmonary function. Participants in the highest decile of
      1,4-DCB concentration had decrements of -153 mL [95% confidence interval (CI) , 
      297 to -8] in forced expiratory volume in 1 sec and -346 mL/sec (95% CI, -667 to 
      24) in maximum mid-expiratory flow rate, compared with participants in the lowest
      decile. CONCLUSIONS: Exposure to 1,4-DCB, a VOC related to the use of air
      fresheners, toilet bowl deodorants, and mothballs, at levels found in the U.S.
      general population, may result in reduced pulmonary function. This common
      exposure may have long-term adverse effects on respiratory health.

PMID- 16882528
TI  - Coarse particles and heart rate variability among older adults with coronary
      artery disease in the Coachella Valley, California.
AB  - Alterations in cardiac autonomic control, assessed by changes in heart rate
      variability (HRV), provide one plausible mechanistic explanation for consistent
      associations between exposure to airborne particulate matter (PM) and increased
      risks of cardiovascular mortality. Decreased HRV has been linked with exposures
      to PM10 (PM with aerodynamic diameter<or=10 microm) and with fine particles (PM
      with aerodynamic diameter<or=2.5 microm) originating primarily from combustion
      sources. However, little is known about the relationship between HRV and coarse
      particles [PM with aerodynamic diameter 10-2.5 microm (PM10-2.5)], which
      typically result from entrainment of dust and soil or from mechanical abrasive
      processes in industry and transportation. We measured several HRV variables in 19
      nonsmoking older adults with coronary artery disease residing in the Coachella
      Valley, California, a desert resort and retirement area in which ambient PM10
      consists predominantly of PM10-2.5. Study subjects wore Holter monitors for 24 hr
      once per week for up to 12 weeks during spring 2000. Pollutant concentrations
      were assessed at nearby fixed-site monitors. We used mixed models that controlled
      for individual-specific effects to examine relationships between air pollutants
      and several HRV metrics. Decrements in several measures of HRV were consistently
      associated with both PM10 and PM10-2.5; however, there was little relationship of
      HRV variables with PM2.5 concentrations. The magnitude of the associations
      (approximately 1-4% decrease in HRV per 10-microg/m3 increase in PM10 or PM10
      2.5) was comparable with those observed in several other studies of PM. Elevated
      levels of ambient PM10-2.5 may adversely affect HRV in older subjects with
      coronary artery disease.

PMID- 16882529
TI  - Mycotoxin adducts on human serum albumin: biomarkers of exposure to Stachybotrys
      chartarum.
AB  - OBJECTIVE: Despite the growing body of evidence showing adverse health effects
      from inhalation exposure to the trichothecene-producing mold Stachybotrys
      chartarum, controversy remains. Currently, there are no reliable assays suitable
      for clinical diagnosis of exposure. We hypothesized that satratoxin G (SG) 
      albumin adducts may serve as biomarkers of exposure to this fungus. DESIGN: We
      studied the formation of adducts of SG with serum albumin in vitro using Western
      blots and mass spectrometry (MS) and searched for similar adducts formed in vivo
      using human and animal serum. RESULTS: Samples of purified human serum albumin
      that had been incubated with increasing concentrations of SG showed concentration
      dependent albumin bands in Western blots developed with anti-SG antibodies. MS
      analysis found that as many as 10 toxin molecules can be bound in vitro to one
      albumin molecule. The sequencing of albumin-adduct tryptic peptides and the
      analysis of pronase/aminopeptidase digests demonstrated that lysyl, cysteinyl,
      and histidyl residues are involved in the formation of these adducts. Serum
      samples from three patients with documented exposure to S. chartarum similarly
      revealed lysine-, cysteine-, and histidine-SG adducts after exhaustive digestion,
      affinity column enrichment, and MS analysis. These adducts were also found in the
      sera from rats exposed to the spores of S. chartarum in contrast to control human
      subjects and control animals. CONCLUSIONS: These data document the occurrence of
      SG-albumin adducts in both in vitro experiments and in vivo human and animal
      exposures to S. chartarum. RELEVANCE TO CLINICAL PRACTICE: SG-amino acid adducts
      may serve as reliable dosimeter biomarkers for detection of exposure to S.
      chartarum.

PMID- 16882530
TI  - Ozone and daily mortality in Shanghai, China.
AB  - BACKGROUND: Controversy remains regarding the relationship between ambient ozone
      and mortality worldwide. In mainland China, the largest developing country, there
      has been no prior study investigating the acute effect of O3 on death risk. Given
      the changes in types of air pollution from conventional coal combustion to the
      mixed coal combustion/motor vehicle emissions in China's large cities, it is
      worthwhile to investigate the acute effect of O3 on mortality outcomes in the
      country. OBJECTIVES: We conducted a time-series study to investigate the relation
      between O3 and daily mortality in Shanghai using 4 years of daily data (2001
      2004). METHODS: We used the generalized additive model with penalized splines to
      analyze mortality, O3 pollution, and covariate data in warm and cold seasons. We
      considered daily counts of all-cause mortality and several cause-specific
      subcategories (respiratory and cardiovascular). We also examined these
      associations among several subpopulations based on age and sex. RESULTS: O3 was
      significantly associated with total and cardiovascular mortality in the cold
      season but not in the warm season. In the whole-year analysis, an increase of 10
      microg/m3 of 2-day average (lag01) O3 corresponds to 0.45% [95% confidence
      interval (CI) , 0.16-0.73%], 0.53% (95% CI, 0.10-0.96%), and 0.35% (95% CI, -0.40
      to 1.09%) increase of total nonaccidental, cardiovascular, and respiratory
      mortality, respectively. In the cold season, the estimates increased to 1.38%
      (95% CI, 0.68-2.07%), 1.53% (95% CI, 0.54-2.52%), and 0.95% (95% CI, -0.71 to
      2.60%), respectively. In the warm season, we did not observe significant
      associations for both total and cause-specific mortality. The results were
      generally insensitive to model specifications such as lag structure of O3
      concentrations and degree of freedom for time trend. Multipollutant models
      indicate that the effect of O3 was not confounded by particulate matter<or=10
      microm in diameter (PM10) or by sulfur dioxide; however, after adding nitrogen
      dioxide into the model, the association of O3 with total and cardiovascular
      mortality became statistically insignificant. CONCLUSIONS: O3 pollution has
      stronger health effects in the cold than in the warm season in Shanghai. Our
      analyses also strengthen the rationale for further limiting levels of O3
      pollution in outdoor air in the city.

PMID- 16882531
TI  - Lead exposure is associated with decreased serum paraoxonase 1 (PON1) activity
      and genotypes.
AB  - Lead exposure causes cardiac and vascular damage in experimental animals.
      However, there is considerable debate regarding the causal relationship between
      lead exposure and cardiovascular dysfunction in humans. Paraoxonase 1 (PON1), a
      high-density lipoprotein-associated antioxidant enzyme, is capable of hydrolyzing
      oxidized lipids and thus protects against atherosclerosis. Previous studies have
      shown that lead and several other metal ions are able to inhibit PON1 activity in
      vitro. To investigate whether lead exposure has influence on serum PON1 activity,
      we conducted a cross-sectional study of workers from a lead battery manufactory
      and lead recycling plant. Blood samples were analyzed for whole-blood lead
      levels, serum PON1 activity, and three common PON1 polymorphisms (Q192R, L55M, 
      108C/T). The mean blood lead level (+/-SD) of this cohort was 27.1+/-15
      microg/dL. Multiple linear regression analysis showed that blood lead levels were
      significantly associated with decreased serum PON1 activity (p<0.001) in lead
      workers. This negative correlation was more evident for workers who carry the
      R192 allele, which has been suggested to be a risk factor for coronary heart
      disease. Taken together, our results suggest that the decrease in serum PON1
      activity due to lead exposure may render individuals more susceptible to
      atherosclerosis, particularly subjects who are homozygous for the R192 allele.

PMID- 16882532
TI  - Application of cryopreserved human hepatocytes in trichloroethylene risk
      assessment: relative disposition of chloral hydrate to trichloroacetate and
      trichloroethanol.
AB  - BACKGROUND: Trichloroethylene (TCE) is a suspected human carcinogen and a common
      groundwater contaminant. Chloral hydrate (CH) is the major metabolite of TCE
      formed in the liver by cytochrome P450 2E1. CH is metabolized to the
      hepatocarcinogen trichloroacetate (TCA) by aldehyde dehydrogenase (ALDH) and to
      the noncarcinogenic metabolite trichloroethanol (TCOH) by alcohol dehydrogenase
      (ADH). ALDH and ADH are polymorphic in humans, and these polymorphisms are known
      to affect the elimination of ethanol. It is therefore possible that polymorphisms
      in CH metabolism will yield subpopulations with greater than expected TCA
      formation with associated enhanced risk of liver tumors after TCE exposure.
      METHODS: The present studies were undertaken to determine the feasibility of
      using commercially available, cryogenically preserved human hepatocytes to
      determine simultaneously the kinetics of CH metabolism and ALDH/ADH genotype.
      Thirteen human hepatocyte samples were examined. Linear reciprocal plots were
      obtained for 11 ADH and 12 ALDH determinations. RESULTS: There was large
      interindividual variation in the Vmax values for both TCOH and TCA formation.
      Within this limited sample size, no correlation with ADH/ALDH genotype was
      apparent. Despite the large variation in Vmax values among individuals,
      disposition of CH into the two competing pathways was relatively constant.
      CONCLUSIONS: These data support the use of cryopreserved human hepatocytes as an
      experimental system to generate metabolic and genomic information for
      incorporation into TCE cancer risk assessment models. The data are discussed with
      regard to cellular factors, other than genotype, that may contribute to the
      observed variability in metabolism of CH in human liver.

PMID- 16882533
TI  - Nested case-control study of autoimmune disease in an asbestos-exposed
      population.
AB  - OBJECTIVE: To explore the potential association between asbestos exposure and
      risk of autoimmune disease, we conducted a case-control study among a cohort of
      7,307 current and former residents of Libby, Montana, a community with historical
      occupational and environmental exposure to asbestos-contaminated vermiculite.
      METHODS: Cases were defined as those who reported having one of three systemic
      autoimmune diseases (SAIDs): systemic lupus erythematosus, scleroderma, or
      rheumatoid arthritis (RA). Controls were randomly selected at a 3:1 ratio from
      among the remaining 6,813 screening participants using frequency-matched age and
      sex groupings. RESULTS: The odds ratios (ORs) and 95% confidence intervals (CIs)
      for SAIDs among those >or=65 years of age who had worked for the vermiculite
      mining company were 2.14 (95% CI, 0.90-5.10) for all SAIDs and 3.23 (95% CI, 1.31
      7.96) for RA. In this age group, exposure to asbestos while in the military was
      also an independent risk factor, resulting in a tripling in risk. Other measures
      of occupational exposure to vermiculite indicated 54% and 65% increased risk for
      SAIDs and RA, respectively. Those who had reported frequent contact with
      vermiculite through various exposure pathways also demonstrated elevated risk for
      SAIDs and RA. We found increasing risk estimates for SAIDs with increasing
      numbers of reported vermiculite exposure pathways (p<0.001). CONCLUSION: These
      preliminary findings support the hypothesis that asbestos exposure is associated
      with autoimmune disease. Refined measurements of asbestos exposure and SAID
      status among this cohort will help to further clarify the relationship between
      these variables.

PMID- 16882534
TI  - Cancer incidence among pesticide applicators exposed to cyanazine in the
      agricultural health study.
AB  - BACKGROUND: Cyanazine is a common pesticide used frequently in the United States
      during the 1980s and 1990s. Animal and human studies have suggested that
      triazines may be carcinogenic, but results have been mixed. We evaluated cancer
      incidence in cyanazine-exposed pesticide applicators among the 57,311 licensed
      pesticide applicators in the Agricultural Health Study (AHS). METHODS: We
      obtained detailed pesticide exposure information from a self-administered
      questionnaire completed at enrollment (1993-1997). Cancer incidence was followed
      through January 2002. Over half of cyanazine-exposed applicators had >or=6 years
      of exposure at enrollment, and approximately 85% had begun using cyanazine before
      the 1990s. We used adjusted Poisson regression to calculate rate ratios (RRs) and
      95% confidence intervals (CIs) of multiple cancer sites among cyanazine-exposed
      applicators. We calculated ptrend values, and all statistical tests were two
      sided. Two exposure metrics were used: tertiles of lifetime days of exposure (LD)
      and intensity-weighted LD. RESULTS: A total of 20,824 cancer-free AHS applicators
      reported ever using cyanazine at enrollment. Cancer incidence comparisons between
      applicators with the lowest cyanazine exposure and those with the highest
      exposure yielded the following for the LD metric: all cancers, RR=0.99 (95% CI,
      0.80-1.24); prostate cancer, RR=1.23 (95% CI, 0.87-1.70); all lymphohematopoietic
      cancers, RR=0.92 (95% CI, 0.50-1.72); non-Hodgkin lymphoma, RR=1.25 (95% CI, 0.47
      3.35); lung cancer, RR=0.52 (95% CI, 0.22-1.25). CONCLUSIONS: We did not find any
      clear, consistent associations between cyanazine exposure and any cancer
      analyzed. The number of sites was small for certain cancers, limiting any
      conclusion with regard to ovarian, breast, and some other cancers.

PMID- 16882535
TI  - Cooperation of the inducible nitric oxide synthase and cytochrome P450 1A1 in
      mediating lung inflammation and mutagenicity induced by diesel exhaust particles.
AB  - Diesel exhaust particles (DEPs) have been shown to activate oxidant generation by
      alveolar macrophages (AMs), alter xenobiotic metabolic pathways, and modify the
      balance of pro-antiinflammatory cytokines. In this study we investigated the role
      of nitric oxide (NO) in DEP-mediated and DEP organic extract (DEPE) -mediated
      inflammatory responses and evaluated the interaction of inducible NO synthase
      (iNOS) and cytochrome P450 1A1 (CYP1A1). Male Sprague-Dawley rats were
      intratracheally (IT) instilled with saline, DEPs (35 mg/kg), or DEPEs (equivalent
      to 35 mg DEP/kg), with or without further treatment with an iNOS inhibitor,
      aminoguanidine (AG; 100 mg/kg), by intraperitoneal injection 30 min before and 3,
      6, and 9 hr after IT exposure. At 1 day postexposure, both DEPs and DEPEs induced
      iNOS expression and NO production by AMs. AG significantly lowered DEP- and DEPE
      induced iNOS activity but not the protein level while attenuating DEPE- but not
      DEP-mediated pulmonary inflammation, airway damage, and oxidant generation by
      AMs. DEP or DEPE exposure resulted in elevated secretion of both interleukin (IL)
      -12 and IL-10 by AMs. AG significantly reduced DEP- and DEPE-activated AMs in IL
      12 production. In comparison, AG inhibited IL-10 production by DEPE-exposed AMs
      but markedly increased its production by DEP-exposed AMs, suggesting that NO
      differentially regulates the pro- and antiinflammatory cytokine balance in the
      lung. Both DEPs and DEPEs induced CYP1A1 expression. AG strongly inhibited CYP1A1
      activity and lung S9 activity-dependent 2-aminoanthracene mutagenicity. These
      studies show that NO plays a major role in DEPE-induced lung inflammation and CYP
      dependent mutagen activation but a lesser role in particulate-induced
      inflammatory damage.

PMID- 16882536
TI  - The OECD program to validate the rat Hershberger bioassay to screen compounds for
      in vivo androgen and antiandrogen responses. Phase 1: use of a potent agonist and
      a potent antagonist to test the standardized protocol.
AB  - The Organisation for Economic Cooperation and Development (OECD) has completed
      phase 1 of the Hershberger validation intended to identify in vivo activity of
      suspected androgens and antiandrogens. Seventeen laboratories from 7 countries
      participated in phase 1, and results were collated and evaluated by the OECD with
      the support of an international committee of experts. Five androgen-responsive
      tissues (ventral prostate, paired seminal vesicles and coagulating glands,
      levator ani and bulbocavernosus muscles, glans penis, and paired Cowper's or
      bulbourethral glands) were evaluated. The standardized protocols used selected
      doses of a reference androgen, testosterone propionate (TP), and an antiandrogen,
      flutamide (FLU). All laboratories successfully detected TP-stimulated increases
      in androgen-responsive tissue weight and decreases in TP-stimulated tissue
      weights when FLU was co-administered. The standardized protocols performed well
      under a variety of conditions (e.g., strain, diet, housing protocol, bedding).
      There was good agreement among laboratories with regard to the TP doses inducing
      significant increases in tissue weights and the FLU doses decreasing TP
      stimulated tissue weights. Several additional procedures (e.g., weighing of the
      dorsolateral prostate and fixation of tissues before weighing) and serum
      component measurements (e.g., luteinizing hormone) were also included by some
      laboratories to assess their potential utility. The results indicated that the
      OECD Hershberger protocol was robust, reproducible, and transferable across
      laboratories. Based on this phase 1 validation study, the protocols have been
      refined, and the next phase of the OECD validation program will test the protocol
      with selected doses of weak androgen agonists, androgen antagonists, a 5alpha
      reductase inhibitor, and chemicals having no androgenic activity.

PMID- 16882537
TI  - Di-(2-ethylhexyl) phthalate enhances atopic dermatitis-like skin lesions in mice.
AB  - Di-(2-ethylhexyl) phthalate (DEHP) has been widely used in polyvinyl chloride
      products and has become ubiquitous in the developed countries. DEHP reportedly
      displays an adjuvant effect on immunoglobulin production. However, it has not
      been elucidated whether DEHP is associated with the aggravation of atopic
      dermatitis. We investigated the effects of DEHP on atopic dermatitis-like skin
      lesions induced by mite allergen in NC/Nga mice. NC/Nga male mice were injected
      intradermally with mite allergen on their right ears. In the presence of
      allergen, DEHP (0, 0.8, 4, 20, or 100 microg) was administered by intraperitoneal
      injection. We evaluated clinical scores, ear thickening, histologic findings, and
      the protein expression of chemokines. Exposure to DEHP at a dose of 0.8-20 microg
      caused deterioration of atopic dermatitis-like skin lesions related to mite
      allergen; this was evident from macroscopic and microscopic examinations.
      Furthermore, these changes were consistent with the protein expression of
      proinflammatory molecules such as macrophage inflammatory protein-1alpha (MIP
      1alpha) and eotaxin in the ear tissue in overall trend. In contrast, 100 microg
      DEHP did not show the enhancing effects. These results indicate that DEHP
      enhances atopic dermatitis-like skin lesions at hundred-fold lower levels than
      the no observed adverse effect level determined on histologic changes in the
      liver of rodents. DEHP could be at least partly responsible for the recent
      increase in atopic dermatitis.

PMID- 16882538
TI  - UMTS base station-like exposure, well-being, and cognitive performance.
AB  - BACKGROUND: Radio-frequency electromagnetic fields (RF EMF) of mobile
      communication systems are widespread in the living environment, yet their effects
      on humans are uncertain despite a growing body of literature. OBJECTIVES: We
      investigated the influence of a Universal Mobile Telecommunications System (UMTS)
      base station-like signal on well-being and cognitive performance in subjects with
      and without self-reported sensitivity to RF EMF. METHODS: We performed a
      controlled exposure experiment (45 min at an electric field strength of 0, 1, or
      10 V/m, incident with a polarization of 45 degrees from the left back side of the
      subject, weekly intervals) in a randomized, double-blind crossover design. A
      total of 117 healthy subjects (33 self-reported sensitive, 84 nonsensitive
      subjects) participated in the study. We assessed well-being, perceived field
      strength, and cognitive performance with questionnaires and cognitive tasks and
      conducted statistical analyses using linear mixed models. Organ-specific and
      brain tissue-specific dosimetry including uncertainty and variation analysis was
      performed. RESULTS: In both groups, well-being and perceived field strength were
      not associated with actual exposure levels. We observed no consistent condition
      induced changes in cognitive performance except for two marginal effects. At 10
      V/m we observed a slight effect on speed in one of six tasks in the sensitive
      subjects and an effect on accuracy in another task in nonsensitive subjects. Both
      effects disappeared after multiple end point adjustment. CONCLUSIONS: In contrast
      to a recent Dutch study, we could not confirm a short-term effect of UMTS base
      station-like exposure on well-being. The reported effects on brain functioning
      were marginal and may have occurred by chance. Peak spatial absorption in brain
      tissue was considerably smaller than during use of a mobile phone. No conclusions
      can be drawn regarding short-term effects of cell phone exposure or the effects
      of long-term base station-like exposure on human health.

PMID- 16882539
TI  - Endocrine disrupting chemicals research program of the U.S. Environmental
      Protection Agency: summary of a peer-review report.
AB  - At the request of the U.S. Environmental Protection Agency (EPA) Office of
      Research and Development, a subcommittee of the Board of Scientific Counselors
      Executive Committee conducted an independent and open peer review of the
      Endocrine Disrupting Chemicals Research Program (EDC Research Program) of the
      U.S. EPA. The subcommittee was charged with reviewing the design, relevance,
      progress, scientific leadership, and resources of the program. The subcommittee
      found that the long-term goals and science questions in the EDC Program are
      appropriate and represent an understandable and solid framework for setting
      research priorities, representing a combination of problem-driven and core
      research. Long-term goal (LTG) 1, dealing with the underlying science surrounding
      endocrine disruptors, provides a solid scientific foundation for conducting risk
      assessments and making risk management decisions. LTG 2, dealing with defining
      the extent of the impact of endocrine-disrupting chemicals (EDCs), has shown
      greater progress on ecologic effects of EDCs compared with that on human health
      effects. LTG 3, which involves support of the Endocrine Disruptor Screening and
      Testing Program of the U.S. EPA, has two mammalian tests already through a
      validation program and soon available for use. Despite good progress, we
      recommend that the U.S. EPA a) strengthen their expertise in wildlife toxicology,
      b) expedite validation of the Endocrine Disruptors Screening and Testing Advisory
      Committee tests, c) continue dependable funding for the EDC Research Program, d)
      take a leadership role in the application of "omics" technologies to address many
      of the science questions critical for evaluating environmental and human health
      effects of EDCs, and e) continue to sponsor multidisciplinary intramural research
      and interagency collaborations.

PMID- 16882540
TI  - Hearing loss in workers exposed to toluene and noise.
AB  - In this study we investigated the risk of hearing loss among workers exposed to
      both toluene and noise. We recruited 58 workers at an adhesive materials
      manufacturing plant who were exposured to both toluene and noise [78.6-87.1 A
      weighted decibels; dB(A)], 58 workers exposed to noise only [83.5-90.1 dB(A)],
      and 58 administrative clerks [67.9-72.6 dB(A)] at the same company. We
      interviewed participants to obtain sociodemographic and employment information
      and performed physical examinations, including pure-tone audiometry tests between
      0.5 and 6 kHz. A contracted laboratory certified by the Council of Labor in
      Taiwan conducted on-site toluene and noise exposure measurements. The prevalence
      of hearing loss of >or=25 dB in the toluene plus noise group (86.2%) was much
      greater than that in the noise-only group (44.8%) and the administrative clerks
      (5.0%) (p<0.001). The prevalence rates were 67.2, 32.8, and 8.3% (p<0.001),
      respectively, when 0.5 kHz was excluded from the estimation. Multivariate
      logistic regression analysis showed that the toluene plus noise group had an
      estimated risk for hearing loss>or=25 dB, 10.9 times higher than that of the
      noise-only group. The risk ratio dropped to 5.8 when 0.5 kHz was excluded from
      the risk estimation. Hearing impairment was greater for the pure-tone frequency
      of 1 kHz than for that of 2 kHz. However, the mean hearing threshold was the
      poorest for 6 kHz, and the least effect was observed for 2 kHz. Our results
      suggest that toluene exacerbates hearing loss in a noisy environment, with the
      main impact on the lower frequencies.

PMID- 16882541
TI  - Effect of prenatal exposure to airborne polycyclic aromatic hydrocarbons on
      neurodevelopment in the first 3 years of life among inner-city children.
AB  - Our prospective cohort study of nonsmoking African-American and Dominican mothers
      and children in New York City is evaluating the role of prenatal exposure to
      urban pollutants, including polycyclic aromatic hydrocarbons (PAHs) ,
      environmental tobacco smoke (ETS) , and pesticides, in the pathogenesis of
      neurobehavioral disorders. We used the Bayley Scales of Infant Development to
      evaluate the effects on child mental and psychomotor development of prenatal
      exposure to airborne PAHs monitored during pregnancy by personal air sampling.
      Behavioral development was assessed by the Child Behavior Checklist. We adjusted
      for potential confounders including sociodemographic factors and prenatal
      exposure to ETS and chlorpyrifos. Prenatal exposure to PAHs was not associated
      with psychomotor development index or behavioral problems. However, high prenatal
      exposure to PAHs (upper quartile) was associated with lower mental development
      index at age 3 [beta=-5.69; 95% confidence interval (CI), -9.05 to -2.33;
      p<0.01]. The odds of cognitive developmental delay were also significantly
      greater for children with high prenatal exposure (odds ratio=2.89; 95% CI, 1.33
      to 6.25; p=0.01). General estimated equation analysis showed a significant age
      times PAH effect on mental development (p=0.01), confirming the age-specific
      regression findings. Further adjustment for lead did not alter the relationships.
      There were no differences in effect sizes by ethnicity. The results require
      confirmation but suggest that environmental PAHs at levels recently encountered
      in New York City air may adversely affect children's cognitive development at 3
      years of age, with implications for school performance.

PMID- 16882542
TI  - Increased mortality from lung cancer and bronchiectasis in young adults after
      exposure to arsenic in utero and in early childhood.
AB  - Arsenic in drinking water is an established cause of lung cancer, and preliminary
      evidence suggests that ingested arsenic may also cause nonmalignant lung disease.
      Antofagasta is the second largest city in Chile and had a distinct period of very
      high arsenic exposure that began in 1958 and lasted until 1971, when an arsenic
      removal plant was installed. This unique exposure scenario provides a rare
      opportunity to investigate the long-term mortality impact of early-life arsenic
      exposure. In this study, we compared mortality rates in Antofagasta in the period
      1989-2000 with those of the rest of Chile, focusing on subjects who were born
      during or just before the peak exposure period and who were 30-49 years of age at
      the time of death. For the birth cohort born just before the high-exposure period
      (1950-1957) and exposed in early childhood, the standardized mortality ratio
      (SMR) for lung cancer was 7.0 [95% confidence interval (CI), 5.4-8.9; p<0.001]
      and the SMR for bronchiectasis was 12.4 (95% CI, 3.3-31.7; p<0.001). For those
      born during the high-exposure period (1958-1970) with probable exposure in utero
      and early childhood, the corresponding SMRs were 6.1 (95% CI, 3.5-9.9; p<0.001)
      for lung cancer and 46.2 (95% CI, 21.1-87.7; p<0.001) for bronchiectasis. These
      findings suggest that exposure to arsenic in drinking water during early
      childhood or in utero has pronounced pulmonary effects, greatly increasing
      subsequent mortality in young adults from both malignant and nonmalignant lung
      disease.

PMID- 16882543
TI  - PAH-DNA adducts in cord blood and fetal and child development in a Chinese
      cohort.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are an important class of toxic
      pollutants released by fossil fuel combustion. Other pollutants include metals
      and particulate matter. PAH-DNA adducts, or benzo[a]pyrene (BaP) adducts as their
      proxy, provide a chemical-specific measure of individual biologically effective
      doses that have been associated with increased risk of cancer and adverse birth
      outcomes. In the present study we examined the relationship between prenatal PAH
      exposure and fetal and child growth and development in Tongliang, China, where a
      seasonally operated coal-fired power plant was the major pollution source. In a
      cohort of 150 nonsmoking women and their newborns enrolled between 4 March 2002
      and 19 June 2002, BaP-DNA adducts were measured in maternal and umbilical cord
      blood obtained at delivery. The number of gestational months occurring during the
      period of power plant operation provided a second, more general measure of
      exposure to plant emissions, in terms of duration. High PAH-DNA adduct levels
      (above the median of detectable adduct level) were associated with decreased
      birth head circumference (p=0.057) and reduced children's weight at 18 months, 24
      months, and 30 months of age (p<0.05), after controlling for potential
      confounders. In addition, in separate models, longer duration of prenatal
      exposure was associated with reduced birth length (p=0.033) and reduced
      children's height at 18 (p=0.001), 24 (p<0.001), and 30 months of age (p<0.001).
      The findings suggest that exposure to elevated levels of PAHs, with the Tongliang
      power plant being a significant source, is associated with reduced fetal and
      child growth in this population.

PMID- 16882544
TI  - Effect of prenatal exposure to polychlorinated biphenyls on incidence of acute
      respiratory infections in preschool Inuit children.
AB  - OBJECTIVE: We set out to assess whether environmental prenatal exposure to
      polychlorinated biphenyls (PCBs) is associated with incidence of acute
      respiratory infections in preschool Inuit children. STUDY DESIGN: We reviewed the
      medical charts of 343 children from 0 to 5 years of age and evaluated the
      associations between PCB-153 concentration in umbilical cord plasma and the
      incidence rates of acute otitis media (AOM) and of upper and lower respiratory
      tract infections (URTIs and LRTIs, respectively). RESULTS: The incidence rates of
      AOM and LRTIs were positively associated with prenatal exposure to PCBs. Compared
      with children in the first quartile of exposure (least exposed), children in
      fourth quartile (most exposed) had rate ratios of 1.25 (p<0.001) and 1.40
      (p<0.001) for AOM and LRTIs, respectively. There was no association between
      prenatal PCB exposure and incidence rate of URTIs or hospitalization. CONCLUSION:
      Prenatal exposure to PCBs could be responsible for a significant portion of
      respiratory infections in children of this population.

PMID- 16882545
TI  - Self-dissolving microneedles for the percutaneous absorption of EPO in mice.
AB  - Erythropoietin (EPO) loaded microneedles were prepared using thread-forming
      polymer as a base for the percutaneous administration of EPO. The used polymers
      were dextrin, chondroitin sulfate and albumin. Under room temperature, EPO
      solution was added to high concentration of polymer solution and microneedles
      were prepared by forming thread with polypropylene tips. The mean weight of
      microneedle was 0.59 +/- 0.01 mg and length and basal diameter were 3.24 +/- 0.16
      and 0.55 +/- 0.03 mm, respectively. Four microneedles were percutaneously (pc)
      administered to mice at the EPO dose levels of 100 IU/kg. After administration,
      blood samples were collected for 24 h and serum EPO levels were measured. Dextrin
      EPO microneedles were administered both pc and subcutaneously (sc) to mice. Serum
      EPO levels vs. time profiles showed Cmax of 138.6 +/- 16.1 and 146.5 +/- 8.0
      mIU/ml, respectively. Tmax were 7.5 h. The values of bioavailability (BA) of EPO
      were 82.1 and 99.4%, respectively. By decreasing the dose from 100 to 50 and 25
      IU/kg, dose-dependent serum EPO levels vs. time profiles were not clearly
      obtained. When chondroitin sulfate and albumin were used as the microneedle base,
      the serum EPO levels vs. time profiles showed almost the same pattern. Cmax of
      chondroitin sulfate and albumin microneedles were 96.3 +/- 8.8 and 132.2 +/- 18.9
      mIU/ml, respectively. AUCs were 835.1 and 1098.7 mIU h/ml. Tmax were 8 and 6.8 h.
      These results suggest the usefulness of microneedles for the percutaneous
      administration of EPO.

PMID- 16882546
TI  - Neuronal affinity of a C7C loop peptide identified through phage display.
AB  - Phage display is a promising tool for the screening of peptides with high
      affinity for specific cells. Here we describe a novel peptide with neuronal
      affinity isolated from a C7C library. We designed a two-tiered biopanning
      strategy initially selecting for ganglioside binding and subsequently selecting
      for binding to PC12 cells. At the completion of biopanning, 54.8% of phage clones
      bore the identical peptide (Tet.C7C.1). Immunofluorescence confirmed selective
      binding of this clone to differentiated PC12 cells. Tet.C7C.1 was synthesized and
      fluorescein conjugated. The synthetic peptide binds neuronal cell lines (SH-SY5Y,
      NSC-34 and PC12 cells) and tissue (DRG and spinal cord). The C7C structure
      creates a loop that minimizes the impact of peptide insertion on the confirmation
      of the recipient protein. Small loop peptides have the ideal characteristics for
      modification of viral vector capsids without undermining genome packaging. The
      neuronal binding properties of this peptide may be applied in the development of
      neurotropic viral vectors.

PMID- 16882547
TI  - ATP-loaded immunoliposomes specific for cardiac myosin provide improved
      protection of the mechanical functions of myocardium from global ischemia in an
      isolated rat heart model.
AB  - Earlier demonstrated cardio-protection by ATP-loaded liposomes (ATP-L) was
      further improved by attachment of cardiac myosin-specific monoclonal 2G4 antibody
      onto the surface of ATP-L. ATP-IL were infused for 1 min duration before starting
      the global ischemia for 25 min followed by reperfusion for 30 min in an isolated
      rat heart. The left ventricular developed pressure at the end of reperfusion in
      ATP-IL group significantly recovered to above 80% of the baseline compared to ca
      25% in the Kreb's-Henseleit (KH) buffer, ca 60% in the IL, and ca 70% in the ATP
      L treated groups. At the end of the reperfusion, left ventricular end diastolic
      pressure significantly reduced to 15 +/- 2 mmHg in ATP-IL group compared to 59 +/
      6 mmHg in the KH buffer, 31 +/- 4 mmHg in the IL and 23 +/- 3 mmHg in the ATP-L
      controls. The extent of preservation depended on the amount of the antibody
      present on the surface of the ATP-IL.

PMID- 16882548
TI  - The brain targeting efficiency following nasally applied MPEG-PLA nanoparticles
      in rats.
AB  - The aim of this study was to encapsulate nimodipine (NM) within methoxy
      poly(ethylene glycol)-poly(lactic acid) (MPEG-PLA) nanoparticles and to
      investigate its brain targeting efficiency following intranasal administration.
      NM-loaded nanoparticles, prepared through an emulsion/solvent evaporation
      technique, were characterized in terms of size, zeta potential, NM loading and in
      vitro release. The nanoparticles were administered intranasally to rats, and the
      concentrations of NM in blood, cerebrospinal fluid (CSF) and brain tissues were
      monitored. The contribution of the olfactory pathway to the uptake of NM in the
      brain was determined by calculating the brain/plasma concentration ratios and
      "brain drug direct transport percentage (DTP)" following intranasal
      administration of the nanoparticles and the solution formulation. The results
      showed that MPEG-PLA nanoparticles had a mean particle size of 76.5 +/- 7.4 nm, a
      negative surface charge and a 5.2% NM loading. In vitro release was moderate
      under sink conditions. The intranasal administration of nanoparticles resulted in
      a low but constant NM level in plasma. The ratio of AUC values of the
      nanoparticles to the solution was 1.56 in CSF. The olfactory bulb/plasma and
      CSF/plasma concentration ratios were significantly higher (P < 0.05) after
      application of nanoparticles than those of the nasal solution, except the ratio
      in olfactory bulb at 5 min. Furthermore, nasally administered nanoparticles
      yielded 1.6-3.3-fold greater DTP values in CSF, olfactory bulb and other brain
      tissues compared to nasal solution. Thus, MPEG-PLA nanoparticles demonstrated its
      potential on improving the efficacy of the direct nose-brain transport for drugs.

PMID- 16882549
TI  - Limited P-glycoprotein mediated efflux for anti-epileptic drugs.
AB  - A variety of anti-epileptic drugs (AEDs) were tested for their ability to be
      transported by P-glycoprotein (P-gp) through Caco-2 monolayers using bi
      directional (apical (Ap) to basolateral (Bas), and Bas to Ap) studies. Transport
      rates were equivalent in both directions for vigabatrin, gabapentin,
      phenobarbitone, lamotrigine and carbamazepine, being 0.7 x 10- 6, 0.1 x 10- 6, 34
      x 10- 6, 36 x 10- 6 and 55 x 10- 6 cm/s, respectively. Phenytoin displayed a 20%
      increase in Ap to Bas transport, while topiramate and ethosuximide each had
      greater transport in the uptake direction, with both drugs showing no efflux.
      None of the transport rates for these drugs were affected by P-gp inhibitors.
      However, the efflux rate for acetazolamide was 3-fold higher than its uptake and
      this was significantly reduced by P-gp inhibitors. Thus, only one anti-epileptic,
      acetazolamide, was shown to be weak P-gp substrate, suggesting that P-gp efflux
      may not be a factor in relation to the development of resistance of epilepsy
      therapy.

PMID- 16882550
TI  - Liposomes as targeted drug delivery systems in the treatment of breast cancer.
AB  - Solid tumors such as breast cancer have historically provided many challenges to
      anti-cancer therapy. Therapeutic hurdles to drug penetration in solid tumors
      include heterogeneous vascular supply and high interstitial pressures within
      tumor tissue, particularly in necrotic zones, lower pH and presence of leaky
      vasculature leading to reduced therapeutic response. Liposome based drug delivery
      systems offer the potential to enhance the therapeutic index of anti-cancer
      agents, either by increasing the drug concentration in tumor cells and/or by
      decreasing the exposure in normal tissues exploiting enhanced permeability and
      retention effect phenomenon and by utilizing targeting strategies. This review
      discusses recent trends in liposome-based drug delivery system both for diagnosis
      and treatment of breast cancer.

PMID- 16882551
TI  - Oral gene delivery: Strategies to improve stability of pDNA towards intestinal
      digestion.
AB  - PURPOSE: Gastrointestinal (GI) nucleases are responsible for a rapid presystemic
      degradation of orally administered transgenes. Within the current study, the
      activity of these degrading enzymes as well as the effect of various nuclease
      inhibitors on the degradation process were evaluated in order to assess their
      potential as auxiliary agents in oral gene delivery. METHODS: Digestion assays of
      pDNA with DNaseI and in GI juices were performed in absence and presence of
      inhibitors. Consequently, a chitosan conjugate with covalently bound
      ethylendiaminetetraacetic acid disodium salt dihydrat (EDTA) was synthesized and
      its nuclease inhibitory properties were evaluated. RESULTS: Small intestinal
      juice was shown to possess a nuclease activity per millilitre corresponding to
      0.02 Kunitz units of DNaseI. Inhibition studies revealed that inhibitory activity
      followed the ranking: EDTA > sodium dodecyl sulfate (SDS) > aurintricarboxylic
      acid (ATA) > poly (acrylic acid) > cysteine. The chitosan-EDTA conjugate offered
      good nuclease inhibiting properties. CONCLUSION: This study determined the
      nuclease activity of native porcine small intestinal juice as well as enterocytes
      homogenate. Moreover, several promising strategies to overcome this enzymatic
      barrier were identified.

PMID- 16882553
TI  - Laterality and accident proneness: a study of locomotive drivers.
AB  - This study attempted to find the association between four measures of laterality
      (handedness, footedness, eyedness, and earedness) and accident proneness in
      locomotive drivers. The Sidedness Bias Schedule was administered to a sample of
      80 locomotive drivers to ascertain their preferential bias. Their accident
      records were also available. Positive correlations were mostly found between the
      measures of hand, foot, ear, and eye dominance. Analyses suggested that there was
      a higher accident rate among left-handers and left-footers, with multiple
      regression unable to determine whether handedness or footedness was related more
      strongly to accident proneness. However, it was clear that accident rate was
      primarily associated with direction of lateralisation, and not with degree of
      lateralisation. Drivers with left-handedness were more likely to be involved in
      accidents, and it is possible that that may be related to the design of the
      locomotive cabs.

PMID- 16882552
TI  - Zonula occludens toxin synthetic peptide derivative AT1002 enhances in vitro and
      in vivo intestinal absorption of low molecular weight heparin.
AB  - Zonula occludens toxin (Zot) is an enterotoxin obtained from the bacterium vibrio
      cholerae that has been shown to reversibly and safely open the tight junctions
      and enhance paracellular transport. AT1002 is a novel synthetic hexapeptide
      derived from Zot. The hypothesis to be tested in this study is that AT1002
      enhances the oral absorption of ardeparin, a low molecular weight heparin (LMWH).
      To test this hypothesis, drug transport through Caco-2 cell monolayers was
      monitored in the presence and absence of AT1002. Regional permeability studies
      using rat intestine were performed. Cell viability in the presence of various
      concentrations of enhancer was determined. The absorption of ardeparin after oral
      administration in rats was measured by anti-factor Xa assay. Furthermore, the
      eventual mucosal and epithelial damage was histologically evaluated. Higher
      ardeparin permeability (approximately 2-fold) compared to control was observed in
      the presence of 0.025% of AT1002. Regional permeability studies revealed that the
      permeability of ardeparin across the duodenal membrane was improved by the
      AT1002. Cell viability studies showed no significant cytotoxicity below 0.0028%
      of AT1002. In the presence of 100 microg/kg of AT1002, ardeparin oral
      bioavailability was significantly increased (F(relative/s.c) approximately
      20.5%). Furthermore, AT1002 at a dose of 100 microg/kg did not induce any
      observable morphological damage on gastrointestinal (GI) tissues in vivo. These
      in vivo and in vitro results suggest that the co-administration of LMWH with
      AT1002 may be a useful delivery strategy to increase its permeability and hence
      oral absorption.

PMID- 16882554
TI  - The relationship between hand preference consistency, health, and accidents in a
      sample of adults over the age of 65 years.
AB  - As a result of the Coren and Halpern (1991) hypothesis that left hand preference
      may be associated with decreased survival fitness, there has been interest in
      exploring the relationship between hand preference and indices of health status.
      In a series of studies of university-aged adults, Hicks and his colleagues found
      a higher prevalence of accidental injuries, falls, and sleep problems among
      individuals with mixed, rather than left, hand preference. They argued that hand
      preference consistency, not side, may be a marker for possible reduction in
      health and well-being. We looked at the relationship between hand preference
      consistency and the prevalence of sleep problems, accidental injuries, falls,
      injuries from falls, and the prevalence of autoimmune and other illnesses in a
      sample of 1277 adults between the ages of 65 and 100 years. Of those participants
      who reported a recent fall, mixed-handers were more likely to report a higher
      number of injuries from these falls when compared to the reports of consistent
      handers. In contrast to the previous findings of Hicks et al., and highlighting
      the value of including broader age ranges, all other comparisons showed no
      differences between the two hand preference types.

PMID- 16882555
TI  - Hand skill and hand-eye preference in relation to verbal ability in healthy adult
      male and female right-handers.
AB  - Verbal as well as non-verbal performances were investigated in relation to both
      hand skill assessed by finger-tapping performances and hand-eye preference in 83
      healthy adult right-handers, most of them students. The primary objective of this
      study was to show better finger-tapping performances in right-handed participants
      with best verbal IQ values. We found that it was not the non-verbal but the
      verbal abilities that were related to finger-tapping performances. This was
      proven, especially as to the left-hand taps. Faster left-hand taps in
      participants with higher verbal IQ values may be due to a closer cooperation of
      right-hemispheric regions in information processing and an intimate relationship
      between language and finger-motor functions. Secondary objectives assessed by
      explorative data analyses included gender differences and hand-eye preference.
      While in the females left-hand taps correlated somewhat more with verbal IQ
      values, in the males this effect was seen in selected variables of the right-hand
      taps. Moreover, laterality assessed in finger-tapping performances may not be in
      accordance with laterality found in the handedness questionnaire. In addition to
      this, congruent hand-eye dominance was found to be slightly more prevalent in
      participants with best verbal IQ values. However, these findings will have to be
      confirmed in further experiments.

PMID- 16882556
TI  - Laterality and language experience.
AB  - A meta-analysis was conducted on studies that examined hemispheric functional
      asymmetry for language in brain-intact monolingual and bilingual adults. Data
      from 23 laterality studies that directly compared bilingual and monolingual
      speakers on the same language were analysed (n = 1234). Variables examined were
      language experience (monolingual, bilingual), experimental paradigm (dichotic
      listening, visual hemifield presentation, and dual task) and, among bilinguals,
      the influence of second language proficiency (proficient vs nonproficient) and
      onset of bilingualism (early, or before age 6; and late, or after age 6).
      Overall, monolinguals and late bilinguals showed reliable left hemisphere
      dominance, while early bilinguals showed reliable bilateral hemispheric
      involvement. Within bilinguals, there was no reliable effect of language
      proficiency when age of L2 acquisition was controlled. The findings indicate that
      early learning of one vs. two languages predicts divergent patterns of cerebral
      language lateralisation in adulthood.

PMID- 16882557
TI  - Reaching patterns across working space: the effects of handedness, task demands,
      and comfort levels.
AB  - Two experiments are reported which examine skill demands, location, and perceived
      comfort levels for a preferential reaching test with left- and right-handed
      participants. In Experiment 1, the effect of task demands was examined by having
      participants perform tasks of varying difficulty with tools (Lift, Pantomime, and
      Use) that were placed in an array in working space. Preferred hand reaches
      predominated at the midline and ipsilateral positions, and decreased
      significantly for contralateral positions, where the frequency of preferred hand
      reaches increased with task difficulty. In Experiment 2 we developed a new
      measure (the Comfort Rating Scale) to rate the subjective feeling of comfort for
      reaching movements. Using the same array of tools and tasks, participants were
      instructed which hand to use to perform reaching movements, and then rated how
      the movement felt. The preferred hand was always rated as being comfortable,
      whereas the non-preferred hand was sensitive to the effects of task demands and
      tool position. The ratings showed that it was the level of comfort with the non
      preferred hand, rather than with the preferred hand, that contributed to the
      patterns seen on the first study. The Comfort Rating Scale provides new insight
      into the distribution of reaching movements within working space.

PMID- 16882558
TI  - G.B. Elion (1918-1999) and G.H. Hitchings (1905-1998): breakthrough in the
      treatment of childhood leukaemia.

PMID- 16882559
TI  - Psychiatric and psychosomatic symptoms are increasing problems among Swedish
      schoolchildren.
AB  - Paediatricians and other professionals in Sweden note that the amount of children
      with psychiatric and psychosomatic symptoms is growing in number. Suicide
      attempts among the young (15-24 y) increased by more than 30% from 1998-2003. The
      Swedish National Board for Health and Welfare's 2004 guidelines for school
      healthcare shed light on this increasing problem among schoolchildren. An article
      in this issue of Acta Paediatrica, "Living conditions and psychosomatic
      complaints in Swedish schoolchildren", analyses economic stress as a causative
      factor leading to psychosomatic symptoms such as headache, abdominal pain and
      difficulty in falling asleep. Living conditions, however, most likely include
      other factors related to our modern and ever-changing society that also have an
      impact on the growing child. CONCLUSION: Psychiatric health is changing for the
      worse among Swedish schoolchildren. The cause is multifactorial. Economic stress
      is one factor, but there are also other possible causes related to modern society
      that correlate to the increase of psychosomatic problems among schoolchildren.
      Three major problems are among those suspected: impaired education and deficient
      working environment in Swedish schools, a general lack of adult contact and
      guidance, and excessive computer and TV use.

PMID- 16882560
TI  - Rapid infancy weight gain and subsequent obesity: systematic reviews and hopeful
      suggestions.
AB  - In a systematic review, we identified 21 separate studies with data on the
      association between rapid infancy weight gain, up to age 2 y, and subsequent
      obesity risk. Uniformly all studies reported significant positive associations.
      We transformed the reported effect sizes to a standard infancy weight gain
      exposure, and found that further differences in study design accounted for much
      of the variation in risk. An accompanying paper by Melinda Yeung reminds us that
      there are benefits of postnatal catch-up growth in certain populations, and
      suggests that genetic and nutritional factors could moderate the unhealthy
      translation of rapid infancy weight gain to visceral fat and insulin resistance.
      Further evidence is needed, and we will need to rigorously test the benefits and
      risks of any interventions. However, the concept of "healthy" rapid catch-up
      infancy growth is an attractive prospect. CONCLUSION: Rapid infancy weight gain
      is consistently associated with increased subsequent obesity risk, but the
      predictive ability of different weight gain cut-offs needs to be tested.

PMID- 16882561
TI  - Postnatal growth, neurodevelopment and altered adiposity after preterm birth-
      from a clinical nutrition perspective.
AB  - Evidence reveals a dilemma that under-nutrition and growth retardation during
      brain growth are associated with neurodevelopmental deficits, and nutritional
      supplement resulting in catch-up growth and relative visceral adiposity leads to
      metabolic/cardiovascular morbidities. Hyperinsulinaemia secondary to insulin
      resistance appears to play a central role in the development of visceral
      adiposity through its action on adipocyte beta3-adrenoceptor. CONCLUSION: Optimal
      nutritional management to minimize hyperinsulinaemia and insulin resistance may
      potentially improve neurodevelopment and facilitate catch-up growth with normal
      body composition.

PMID- 16882562
TI  - Glutamate in current paediatric amino acid solutions is not toxic.
AB  - AIM: To discuss the viewpoint article "How much glutamate is toxic in paediatric
      parenteral nutrition?" Acta Paediatr 2005;94;16-9. CONCLUSION: There is no doubt
      that glutamate used at high bolus doses in animal experiments would permanently
      damage brain cells. However, these effects should not be extrapolated to the
      condition of parenteral nutrition of newborn infants when much smaller amounts of
      glutamate are infused constantly during 24 h. Clinical studies proving the
      maintenance of plasma glutamate concentrations within the reference range during
      parenteral nutrition were not considered. The authors have alarmed neonatologists
      with arguments without substance.

PMID- 16882563
TI  - Medical follow-up visits in adults 5-25 years after treatment for childhood acute
      leukaemia, lymphoma or Wilms' tumour.
AB  - AIM: One aspect of organizing medical follow-up for adult survivors of childhood
      cancer is to determine to what extent the former patient experiences a need for
      health services. In the present paper, we studied how the healthcare needs, both
      subjectively and objectively, were fulfilled for our former patients. METHODS:
      335 survivors over 18 y of age, with a follow-up time of more than 5 y after
      completion of therapy, were sent a questionnaire probing their present use of
      health services. RESULTS: The response rate was 73%. A majority (60%) of the
      survivors had no regular follow-up visits, and 42% of these reported that they
      missed not having one. More than one third were thus far dissatisfied with the
      follow-up programme. Only 3% of those who had regular follow-ups found them
      "unnecessary". Complaints subjectively related to their diseases or treatments
      were reported by 47%. Out of all responders, 34% did not miss having regular
      follow-up visits. Neither perceived disease-related complaints nor radiation
      therapy was a predictor for having a scheduled follow-up visit. CONCLUSION: In
      the absence of a long-term follow-up programme, many survivors were not receiving
      proper medical healthcare, whether from their perspective or from a professional
      one.

PMID- 16882564
TI  - Living conditions and psychosomatic complaints in Swedish schoolchildren.
AB  - BACKGROUND: The proportion of Swedish schoolchildren that reports psychosomatic
      complaints has increased during recent decades, parallel to major structural
      changes in Swedish society. AIM: To investigate the association of psychosomatic
      complaints in relation to household socio-economic conditions. METHODS: Cross
      sectional study based on data from child supplements linked to nationally
      representative household surveys in Sweden during 2000-2003, covering a sample of
      5390 children aged 10-18 y. Symptom variables were based on child interviews,
      while data from parental interviews were used to create socio-economic variables.
      RESULTS: Girls more often reported headache and recurrent abdominal pain (RAP)
      than boys, and these differences became more pronounced with age. Economic stress
      in the household was associated with headache (OR 1.21, p<0.05), RAP (OR 1.46,
      p<0.001) as well as difficulties falling asleep (OR 1.35, p<0.01), while there
      were no consistent associations between symptoms and social class or unemployed
      parents. Children in single-parent families consistently reported somewhat more
      symptoms than children in two-parent families (OR 1.26 for at least two of the
      three symptoms, p<0.05). CONCLUSION: Economic stress, but not social class, was a
      significant but moderate risk factor for all three psychosomatic symptoms. It is
      possible that a growing proportion of families in economic stress has contributed
      to the parallel increase in reported psychosomatic complaints among Swedish
      schoolchildren. Further studies are needed to clarify the relation between lack
      of money, relational strain/support and psychosomatic complaints.

PMID- 16882565
TI  - Evaluation of psychosomatic stress in children by measuring salivary chromogranin
      A.
AB  - AIM: To investigate the usefulness of salivary chromogranin A (CgA) and cortisol
      as stress markers, and the effects of distraction on the suppression of stress in
      children. METHODS: We examined salivary CgA and cortisol responses before and
      after venipuncture in hospitalized children with and without distraction using a
      kaleidoscope. RESULTS: Salivary CgA levels immediately after venipuncture were
      significantly higher than those immediately before it, and at 60 min after
      venipuncture they were significantly lower than those immediately after it.
      However, salivary cortisol showed no significant differences at any of the three
      time points. In contrast, distracted by the kaleidoscope, there were no
      significant differences in salivary CgA and cortisol levels at all three time
      points. CONCLUSION: In children, salivary CgA level is a useful marker of stress.
      As an index of the effect of distraction, the measurement of salivary CgA is
      useful.

PMID- 16882566
TI  - Self-reported headache in schoolchildren: parents underestimate their children's
      headaches.
AB  - BACKGROUND: Most previous studies of childhood headache have used indirect
      parental/physician reports to estimate the prevalence of headache in children.
      AIM: To use direct information from children and to compare the results with data
      collected from parents. STUDY DESIGN/METHODS: A cross-sectional questionnaire was
      sent to parents of 7-12-y-olds in Oslo, Norway. The questionnaire included
      retrospective reports by the parents of the presence of headache among their
      children during the past 6 mo. A panel study was subsequently done with daily
      diaries completed by the children over 6 wk. This was done at school. RESULTS:
      For 2126 children, both diary reports and parental reports were available. We
      found a 1-mo prevalence of self-reported headache of 57.6%. Parents, particularly
      fathers, reported lower headache prevalence than the children. The difference
      between parental reports and those of the children was larger when the child was
      a girl. There was a clear difference for the youngest children and parental
      underreporting for children with the most frequent headaches. CONCLUSION: Since
      indirect parental reports of child headache underestimated headache frequency
      compared to direct diary-based self-reports, we suggest more widespread use of
      diary registration of headaches in studies of child headache.

PMID- 16882567
TI  - Prevalence of recurrent complaints of pain among Greek schoolchildren and
      associated factors: a population-based study.
AB  - AIM: To determine the prevalence of recurrent complaints of pain (RCP) in Greek
      children, and to examine associations with socio-demographic characteristics and
      psychosocial factors. METHODS: Cross-sectional study comprising a nationally
      representative population of 8130 7-y-old Greek schoolchildren. Data were
      collected by mailed questionnaires (response rate 89%). RCP was defined as
      present if at least one of the complaints of headache, abdominal pain or limb
      pain occurred at least once a week. RESULTS: The RCP prevalence rate was 7.2%,
      with significant gender differences (8.8% of girls, 5.7% of boys; p<0.001). RCP
      was significantly positively associated with a chronic health problem among the
      children, frequent change of residence, poor school performance, often watching
      TV and rarely playing with other children. There were no statistically
      significant associations of RCP with family structure and socio-economic status.
      CONCLUSION: The results are indicative of the prevalence of RCP in Greek
      schoolchildren. This study enlightens the psychosocial component of RCP and
      emphasizes the importance of gathering information on children's social
      background in medical settings.

PMID- 16882568
TI  - The adult sense of coherence scale is applicable to 12-year-old schoolchildren-
      an additional tool in health promotion.
AB  - BACKGROUND: Two principal operations of sense of coherence (SOC) for the study of
      adults have been developed, one consisting of 29 and another consisting of 13
      items. According to these studies, SOC is associated with various aspects of
      perceived health. Also, a 16-item scale for determining SOC in young children
      (<or=10 y) is available. It is unclear from which age on SOC can be studied by
      using any of the scales for adults. AIM: To determine whether the 13-item SOC
      scale for adults is applicable to children 12 y of age. METHODS: Comparable data
      of SOC had been collected by a mail survey directed to adults (mean age 36 y,
      n=706) in 1985. Twelve-year-old children filled in questionnaires in school class
      in 1997 (n=994). RESULTS: SOC score range, mean, median and standard deviation
      (SD), and Cronbach alpha coefficients of the total SOC scale were almost
      identical in children and adults. CONCLUSION: The 13-item SOC scale aimed at
      adults is applicable to children of 12 y of age or older. The SOC scale could be
      a useful additional tool for identifying children with perceived health deficits
      potentially in need of supportive interventions.

PMID- 16882569
TI  - Sleep duration and overweight among Australian children and adolescents.
AB  - AIM: To examine the association between sleep and overweight and waist
      circumference (WC) in children and adolescents. METHODS: Data were from a
      nationally representative sample of 6324 7-15-y-old males and females from the
      Australian Health and Fitness Survey. Associations between sleep duration and
      body mass index (BMI) and WC were examined by analysis of covariance, linear
      regression, and logistic regression. RESULTS: In the total sample, there was a
      significant main effect across sleep-duration categories (<or=8 h, 8-9 h, 9-10 h,
      and >or=10 h) for BMI. Linear regression showed significant age, sex, age-sleep,
      and age-sex-sleep interactions in the total sample. There was an inverse graded
      relationship between sleep and BMI and WC in boys. In boys, there was a 1.6-1.8
      times greater odds of overweight for those who reported 8-9 h or 9-10 h of sleep
      compared to those reporting>or=10 h of sleep. For boys reporting<or=8 h of sleep,
      there was about 3.1 times greater odds of overweight compared to those
      reporting>or=10 h of sleep. In contrast, no significant associations between
      sleep and overweight were found in girls. CONCLUSION: Sleep duration was
      inversely related with overweight in young males but not females.

PMID- 16882570
TI  - Plasma long-chain fatty acids and the degree of obesity in Italian children.
AB  - AIM: To examine whether the plasma levels of long-chain polyunsaturated fatty
      acids (LC-PUFAs) are associated with the degree of obesity in children. METHODS:
      Sixty-seven normolipidaemic obese children, aged 8-12 y, and 67 age- and sex
      matched normal-weight children were included in the study. Obesity was defined in
      accordance with the International Obesity Task Force. BMI z-scores were
      calculated. Fasting blood samples were analysed for insulin, glucose, lipid
      profile and fatty acid (FA) levels (expressed as % total FA). Insulin resistance
      was estimated by homeostatic model assessment (HOMA). RESULTS: Compared with
      normal-weight children, obese children exhibited lower mean plasma total PUFA
      (37.8% vs 39.7%), omega-6 PUFAs (35.0% vs 36.8%) and C22:6omega-3-to-C18:3omega-3
      ratio (5.52 vs 7.61), and higher total monounsaturated FA (26.6% vs 25.0%),
      C18:3omega-3 (0.28% vs 0.25%) and C20:5omega-3 (0.45% vs 0.39%). In obese
      children, the BMI z-score was negatively related to plasma PUFA, omega-3 PUFAs,
      C22:6omega-3, and the C22:6omega-3-to-C20:6omega-6 and C22:6omega-3-to-C18:3omega
      3 ratios, and positively with total saturated FA and C20:3omega-9. CONCLUSION: In
      obese children, plasma LC-PUFA profile may be associated with the degree of
      obesity.

PMID- 16882571
TI  - Assessment of obesity status in outpatients from three disease states.
AB  - AIM: To assess obesity status in patients with cystic fibrosis (CF), human
      immunodeficiency virus (HIV) and various metabolic disorders (MD), through
      comparison against a) UK reference data and b) contemporary healthy children.
      METHODS: Weight, height, waist circumference (WC), and triceps (TRI) and sub
      scapular (SUBS) skinfold thickness were measured in a total of 57 healthy, 49
      HIV, 68 MD and 49 CF children. Using published reference data, standard deviation
      scores (SDS) were calculated. RESULTS: CF patients had weight, height and BMI SDS
      significantly below zero. MD patients had height SDS significantly below, and BMI
      SDS significantly above, zero. Healthy children had BMI SDS significantly above
      zero. In all three patient groups and healthy children, TRI and WC SDS were
      significantly above zero. SUBS SDS was also significantly above zero in patients
      with MD and HIV. WC SDS was greater in patients than in healthy children, but
      only significantly so for the MD children. CONCLUSION: In all three patient
      groups, even those associated with reduced stature or reduced weight, indices of
      fatness were significantly increased relative to reference data. The tendency to
      central fatness was evident in healthy children, but was more extreme in
      patients, especially those with MD.

PMID- 16882572
TI  - Leptin is closely related to body fat in prepubertal children aged 8-11 years.
AB  - BACKGROUND: In adults and obese children, serum leptin concentrations are closely
      related to body fat. AIM: To investigate whether such a relationship between
      leptin concentrations and body fat is also evident in children with a relatively
      normal body composition. METHODS: The study was a cross-sectional population
      study in 170 Caucasian children (91 boys and 79 girls), with a mean age of 9.9+/
      0.6 y (range 8.5-10.9 y) and a mean BMI of 17.4+/-2.6 (range 12.8-28.1). Serum
      leptin was measured and compared to total body fat as determined by dual-energy X
      ray absorptiometry. RESULTS: In the whole population, serum leptin concentrations
      were highly correlated with total body fat (r=0.83, p<0.001). A stepwise forward
      multi-regression analysis revealed that the inclusion of other anthropometrical
      data did not add any significance to the model. Leptin concentrations were
      significantly higher in girls (5.2 ng/ml) than in boys (3.2 mg/ml; p=0.003).
      Gender differences still prevailed (p=0.007) after adjusting for number of
      kilograms of fat tissue. CONCLUSION: This study shows that, already at the young
      age of 9-11 y, an adult-like pattern of regulation of leptin exists. This
      indicates similar risk factor dependency of leptin across all age groups.

PMID- 16882573
TI  - Duration of breastfeeding among first-time mothers in the United States: results
      of a national survey.
AB  - AIM: To determine the characteristics of primiparous women who breastfeed for
      only short periods of time. METHODS: The 2002 National Survey of Family Growth
      was used to analyze the characteristics of a national probability sample of 3229
      first-time US mothers aged 15 to 44 y with children ages 1 to 18 y old, 1960 of
      whom breastfed. Main outcome measures in the cross-sectional study included
      breastfeeding at birth and at 3 mo as determined by in-person, computer-assisted
      interviews conducted by trained female interviewers. RESULTS: Sixty-two percent
      of first-time mothers with singleton live births initiated any breastfeeding and
      36% were still breastfeeding at 3 mo. Those who were older, married, and at
      higher educational levels were significantly more likely to continue
      breastfeeding beyond 3 mo. These same demographic factors were associated with
      differences in breastfeeding rates both early (within the first week of life) and
      consistently over the first 3 mo. In multivariate analyses, only educational
      level remained as a predictor of breastfeeding. CONCLUSION: Targeted
      breastfeeding interventions for young, single, less-educated women are warranted
      in a culturally sensitive context, both prenatally and immediately postpartum, to
      improve the duration of breastfeeding among first-time mothers in the US.

PMID- 16882574
TI  - Total glutamine content in human milk is not influenced by gestational age.
AB  - BACKGROUND: Glutamine may be a conditionally indispensable amino acid in neonates
      and should be given in adequate amounts. Reliable information concerning the
      glutamine content of human milk is lacking. AIM: To assess total glutamine
      content in human milk using a novel analytical procedure, and to evaluate the
      potential influence of time of delivery and lactational stage. METHODS: The
      content of free and protein-bound glutamine was assessed in transitional (days 4
      7 of lactation) and mature (days 29-34) human milk, after preterm (<35 wk of
      gestation, n=20) or term (>37 wk, n=20) delivery. Milk samples were obtained by
      manual expression and stored at <or=70 degrees C. Measurement of protein-bound
      glutamine was performed after stabilization by bis(1,1
      trifluoroacetoxy)iodobenzene (BTI). Free glutamine was detected by HPLC. RESULTS:
      There was no difference concerning glutamine content in human milk after term or
      preterm delivery (median of 5000 vs 4960 micromol/l milk). The protein-bound
      glutamine content decreased with the duration of lactation (6230 vs 4540
      micromol/l milk). Free glutamine accounted for only 3-10% of the protein-bound
      glutamine content. The free glutamine content showed a high variability after
      preterm and term delivery. CONCLUSION: This study presents for the first time
      data on glutamine intake in preterm and term neonates fed human milk. With these
      data, it is possible to formulate adequately composed nutritional therapy for
      infants at risk of glutamine imbalance.

PMID- 16882575
TI  - Ghrelin and cholecystokinin in term and preterm human breast milk.
AB  - AIM: To determine whether ghrelin and cholecystokinin (CCK) are present in
      significant quantities in term and preterm human breast milk, and to identify
      their source. METHODS: Samples were collected from 10 mothers who delivered term
      infants and 10 mothers who delivered preterm infants. Estimated fat content was
      measured. Ghrelin and CCK levels were measured in whole and skim breast milk
      samples using radioimmunoassays (RIA). Reverse transcriptase-polymerase chain
      reaction (RT-PCR) was performed using RNA from human mammary epithelial cells
      (hMECs) and mammary gland with primers specific to ghrelin. RESULTS: The median
      ghrelin level in whole breast milk was 2125 pg/ml, which is significantly higher
      than normal plasma levels. There was a direct correlation between whole milk
      ghrelin levels and estimated milk fat content (r=0.84, p<0.001). Both the mammary
      gland and hMECs produced ghrelin. While CCK was detected in some samples, levels
      were insignificant. Infant gestational age, birthweight, maternal age, and
      maternal pre-pregnancy body mass index did not significantly affect the results.
      CONCLUSION: Ghrelin, but not CCK, is present in breast milk. Since the mammary
      gland produces ghrelin message, and ghrelin levels in breast milk are higher than
      those found in plasma, we conclude that ghrelin is produced and secreted by the
      breast.

PMID- 16882576
TI  - Comparison of the phospholipid classes in human milk in Japanese mothers of term
      and preterm infants.
AB  - BACKGROUND: Phospholipids (PLs) play an essential role in the growth and brain
      development of infants. AIM: To investigate PL composition in human milk (HM),
      including lysophosphatidylcholine, phosphatidylethanolamine,
      phosphatidylinositol, phosphatidylserine, phosphatidylcholine (PC) and
      sphingomyelin (SM), from healthy Japanese mothers. Analyses were performed on
      colostrum, transitional milk and mature milk from mothers of preterm and term
      infants. METHODS: HM samples were collected from mothers of 15 term infants (term
      group) and of 19 preterm infants (preterm group). PL composition was determined
      by two-dimensional thin-layer chromatography in conjunction with phosphorus
      analysis. RESULTS: In both groups, the PL content (% of total lipid) of mature
      milk was significantly lower than in colostrum. SM and PC were the main PLs in
      HM, but in the preterm group, the percentage of SM in mature milk was
      significantly higher and PC in mature milk was significantly lower than in the
      term group. CONCLUSION: The transition from colostrum to mature milk leads to an
      increase in SM and a decrease in PC in the HM of preterm infants, along with a
      decrease in PL content. This is the first report to demonstrate the differences
      in PL composition in HM between mothers of preterm and term infants.

PMID- 16882577
TI  - Fetal and perinatal risk factors for inflammatory bowel disease.
AB  - AIM: To study the influence of specific factors and events during pregnancy and
      the perinatal period on the risk of children developing inflammatory bowel
      disease. METHODS: Population-based national register study. Linkage between the
      Swedish Medical Birth Register and the Swedish Hospital Discharge Register during
      the period 1987 to 2000 identified 455 singleton infants who later developed
      inflammatory bowel disease. Data for these children were compared with data for
      all children born in Sweden during the same period. RESULTS: Smoking during early
      pregnancy reduced the risk of inflammatory bowel disease (odds ratio (OR) 0.71,
      95% CI 0.55-0.91). For ulcerative colitis the odds ratio was 0.70 (95% CI 0.56
      0.86), and for Crohn's disease 0.73 (95% CI 0.58-0.94). Infections during the
      neonatal period seemed to increase the risk of inflammatory bowel disease (OR
      17.6, 95% CI 3.6-51.6), but the number of observed events was small. The other
      factors examined did not influence the risk of inflammatory bowel disease.
      CONCLUSION: Maternal smoking during early pregnancy reduces the risk for the
      child to be hospitalized with a diagnosis of inflammatory bowel disease. Severe
      neonatal infections may increase the risk. Thus, some exposures during the fetal
      and neonatal period seem to affect the risk of inflammatory bowel disease later
      in life.

PMID- 16882578
TI  - Prevalence of the metabolic syndrome in elementary school children.
AB  - AIM: To determine the prevalence of the metabolic syndrome (MS) and its related
      components in elementary-aged school children. METHODS: Three hundred and seventy
      five 7-9-y-old boys (n=182) and girls (n=193) in the eastern Kansas area served
      as participants. Criteria for the MS were the presence of three or more of the
      following components: 1) central obesity (waist circumference>or=90th percentile
      in males and females); 2) elevated triglyceride concentrations (>or=1.13 mmol/l);
      3) low HDL-C concentrations (<or=1.04 mmol/l in males and females); 4) elevated
      blood pressure (systolic and/or diastolic>or=90th percentile, age and gender
      specific); or 5) elevated fasting glucose levels (>or=6.10 mmol/l). RESULTS: The
      prevalence of the MS in this sample was 5%, and was similar across gender and
      race. Fifty percent of the children had no components and 15% had at least two
      components, with elevated blood pressure the most common component (37%).
      CONCLUSION: The MS is prevalent even in young children at rates similarly
      reported in adolescents.

PMID- 16882579
TI  - Home-based therapy for oedematous malnutrition with ready-to-use therapeutic
      food.
AB  - BACKGROUND: Standard recommendations are that children with oedematous
      malnutrition receive inpatient therapy with a graduated feeding regimen. AIM: To
      investigate exclusive home-based therapy for children with oedematous
      malnutrition. METHODS: Children with oedematous malnutrition, good appetite and
      no complications were treated at home with ready-to-use therapeutic food (RUTF)
      and followed up fortnightly for up to 8 wk. SETTING AND PARTICIPANTS: 219
      children aged 1-5 y with oedema enrolled in one of two therapeutic nutritional
      studies in Malawi in 2003-2004. RESULTS: The overall recovery rate was 83%
      (182/219), and the case-fatality rate was 5% (11/219). For children with wasting
      and oedematous malnutrition, 65% (55/85) recovered and 7% (6/85) died. The
      average weight gain was 2.8+/-3.2 g/kg/d (mean+/-SD). CONCLUSION: This
      preliminary observation suggests that children with oedematous malnutrition and
      good appetite may be successfully treated with home-based therapy; a randomized,
      controlled trial to evaluate this is warranted.

PMID- 16882580
TI  - A rare cause of thyroid goitre in a UK adolescent.

PMID- 16882581
TI  - Regarding Luecke T, Pfister S, Duerken M. Neurodevelopmental outcome and
      haematological course of a long-time survivor with homozygous alpha-thalassaemia:
      case report and review of the literature. Acta Paediatr 2005;94:1330-3.

PMID- 16882582
TI  - Waist circumference percentiles for 7-15-year-old Australian children.

PMID- 16882584
TI  - Iron supplements do not always reduce erythrocyte copper-zinc superoxide
      dismutase activity in term, breastfed infants.

PMID- 16882587
TI  - Advances in the management of gout and hyperuricaemia.
AB  - An acute attack of gouty arthritis is one of the most painful experiences
      reported throughout medical history. Therefore it is paramount to initiate
      appropriate therapy quickly in order to terminate the acute phase. This goal can
      be achieved with non-steroidal anti-inflammatory agents, colchicine, or
      corticosteroid-based therapies. Rarely, because of contraindications to these
      agents, only symptomatic treatment can be given until the attack subsides. The
      next step is to lower the serum urate level below the limit of solubility (i.e.,
      below 40.8 mmol/L, or 6.8mg/dL) which reduces recurrences and begins to return
      the total body urate pool to normal. This equally important goal can be achieved
      by uricosuric agents or xanthine oxidase inhibitors, although the latter is
      generally favored. Allopurinol is the agent most commonly preferred because of
      its safety profile and ease of use, but there are known serious allergic
      reactions and untoward side effects that occasionally require discontinuation.
      Febuxostat, a xanthine oxidase inhibitor, and pegylated uricase are new agents
      under development and may be beneficial in these situations or when other
      comorbid conditions prevent the use of conventional treatments. Alcohol and
      dietary consumption are also related to hyperuricemia and acute gout. Recently
      beer, wine, and liquor were studied and the risk of gout varied according to the
      alcohol ingested. Furthermore, recent data sheds light on important dietary
      modifications that may help in the treatment of gout, and dispels certain beliefs
      about protein ingestion and the occurrence of acute gout. As we learn more about
      the associated conditions of hypertriglyceridemia, hypertension, and the
      metabolic syndrome, it may allow the tailoring of medical regimens that directly
      prevent or reduce recurrent attacks of gouty arthritis. There are specific
      approved treatments for these common comorbidities that have parallel effects of
      lowering serum urate levels. These recent findings may be especially important
      for treating refractory cases. While patient education remains a cornerstone to
      ensure compliance, other quality indicators for the management of this disease
      have been reported and should guide the clinician in the treatment of gout and
      result in improved care.

PMID- 16882588
TI  - Increased serum uric acid--a marker of non-gouty widespread pain? A study of
      female patients with inflammatory and non-inflammatory pain.
AB  - OBJECTIVE: To study the relationship between reported chronic pain and the level
      of serum urate (SU) among women with various diagnoses of the musculoskeletal
      system. METHODS: Consecutive female patients (aged 20-70 years, n = 124), at
      rheumatology and rehabilitation practices, with chronic musculoskeletal pain of
      different origins were followed for 1 year after an initial survey of pain,
      lifestyle, quality of life, and disability. Repeated blood samples (including
      urate, creatinine, cholesterol, and glucose) were analysed. Multiple regression
      analysis was performed to explain initial variations in SU level in relation to
      pain and confounding factors. RESULTS: The level of SU was increased among
      individuals with widespread pain (>5 locations) independent of underlying
      diagnoses compared to those with fewer pain sites (270.5 vs. 241.2 micromol/L).
      Serum creatinine, body mass index (BMI), the number of pain locations, and sleep
      disturbances independently contributed to the SU level and explained 43% of the
      variation in SU. Individual variation in SU during 4 months was low. CONCLUSIONS:
      Epidemiological data on the relationship between the extent of body pain and SU
      were confirmed in a clinical setting. Besides known factors such as impaired
      renal function and obesity, widespread pain and sleep disturbances were related
      to an increase in SU. Medication and alcohol intake could not explain the
      findings. Longitudinal studies are necessary to elucidate whether the level of SU
      has any implications for the prognosis of chronic pain.

PMID- 16882590
TI  - Infectious causes of death in patients with rheumatoid arthritis: an autopsy
      study.
AB  - OBJECTIVE: To study mortality from infections and accuracy of pre-mortem
      diagnoses in patients with rheumatoid arthritis (RA) autopsied during a 40-year
      period. METHODS: We investigated infectious causes of death, findings at autopsy,
      and clinicians' estimation of cause of death in 369 consecutively autopsied RA
      and 371 autopsied non-RA patients with same sex, age at death, and year of
      autopsy. We also compiled clinical features of RA patients from medical records
      available and examined the association between these and infectious causes of
      death. RESULTS: Deaths from any infection were more frequent in RA (36%) than in
      non-RA (26%) patients. In both groups, respiratory and urinary tract infections
      were the most common infectious causes of death. More RA patients died from
      urinary tract infections than non-RA patients. In approximately half of the
      patients in both groups, infection as a cause of death was unrecognized before
      death, with no major change occurring over the 40-year study period. CONCLUSIONS:
      Infections, especially respiratory and urinary tract infections, are frequent
      causes of death in RA patients. The high proportion of undiscovered infections as
      a cause of death highlights the diagnostic difficulty. With a decreasing number
      of autopsies being performed at present, greater numbers of infections may be
      under-reported.

PMID- 16882589
TI  - The effect of methotrexate (MTX) on expression of signalling lymphocytic
      activation molecule (SLAM) in patients with rheumatoid arthritis (RA) and its
      role in the regulation of cytokine production.
AB  - OBJECTIVE: To investigate the effect of methotrexate (MTX) on cytokine production
      by activated CD4+ T-cells in patients with rheumatoid arthritis (RA). METHODS:
      The effect of MTX on intracellular expression of interferon-gamma (IFN-gamma) and
      interleukin-4 (IL-4), and cell surface expression of signalling lymphocytic
      activation molecule (SLAM) from freshly isolated peripheral blood mononuclear
      cells (PBMCs), and after in vitro culture with or without MTX, was analysed with
      flow cytometry in 18 patients with RA and 20 healthy controls. RESULTS:
      Intracellular expression of IFN-gamma and IL-4 on freshly isolated CD4+ T-cells
      was significantly higher in patients with RA than in the controls (p<0.05).
      Intracellular expression of both IFN-gamma and IL-4 after culture with MTX was
      significantly lower than those after culture without MTX in patients with RA.
      Although no significant difference was observed in SLAM expression on freshly
      isolated CD4+ T-cells between patients with RA and the controls, MTX
      significantly decreased SLAM expression on both activated IFN-gamma+ and IL
      4+CD4+ T-cells in patients with RA. CONCLUSION: In vitro modulation of the
      cytokine network by MTX, IFN-gamma, and IL-4 is one of the major targets for MTX,
      and production of IFN-gamma and IL-4 by PBMCs may be suppressed by SLAM on
      activated CD4+ T-cell in patients with RA.

PMID- 16882591
TI  - Low-field MRI for assessing synovitis in patients with rheumatoid arthritis.
      Impact of Gd-DTPA dose on synovitis scoring.
AB  - OBJECTIVE: To investigate the impact of a double dose compared to a single dose
      of contrast material in low-field magnetic resonance imaging (MRI) on semi
      quantitative scoring of synovitis in patients with rheumatoid arthritis (RA).
      METHODS: This prospective study included 38 RA patients (23 women and 15 men,
      mean age 51 years). All patients underwent low-field MRI of the hand before
      administration of contrast medium, after intravenous injection of 0.1 mmol/kg
      gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA), and after another dose
      of 0.1 mmol/kg Gd-DTPA. Two readers (A and B) blinded to dosage independently
      scored the single dose and double dose image sets for synovitis according to
      outcome measures in rheumatology (OMERACT) recommendations. Contrast-to-noise
      ratio (CNR) and signal-to-noise ratio (SNR) were also calculated for each set.
      RESULTS: 149 metacarpophalangeal (MCP) joints were evaluated. There was good
      inter-reader agreement for each of the two sets (intra-class correlation
      coefficient of 0.75 for the single dose set and 0.83 for the double dose). Median
      CNR and SNR values were 5.4 and 15.9, respectively, for the single dose set and
      8.5 and 16.6, respectively, for the double dose set (p<0.0001). Single dose set
      mean synovitis scores were 1.7 and 1.6 for readers A and B, respectively. Double
      dose set scores were 1.9 and 2.0, respectively. Thus, higher synovitis scores
      were recorded for the double dose sets than the single dose sets (p<0.005).
      CONCLUSION: In low-field MRI, when evaluating RA, the dose of the contrast
      material influences synovitis scoring. Therefore, dosage of contrast material
      should be taken into consideration when using extremity dedicated low-field MRI.

PMID- 16882592
TI  - The effect of balneotherapy on patients with ankylosing spondylitis.
AB  - OBJECTIVE: To compare the effect of balneotherapy on physical activity and
      quality of life as well as the symptoms of pain and stiffness with exercise alone
      in ankylosing spondylitis (AS) patients. METHODS: A total of 60 patients who had
      a diagnosis of AS according to the modified New York criteria were included in
      the study. The patients were randomly assigned to two groups. In Group I (n = 30)
      the patients received balneotherapy in a therapeutic pool for 30 min once a day
      for 3 weeks. All patients received instructions on the exercise programme, which
      they were requested to repeat once a day for 30 min during the study. The
      patients in this group continued the same exercise programme after the end of the
      balneotherapy protocol to complete a course of 6 months. In Group II the patients
      were given the same exercise protocol but did not receive balneotherapy. Patients
      were evaluated before the start of the study and at 3 weeks and 24 weeks.
      Evaluation parameters were daily and night pain, morning stiffness, the patient's
      global evaluation and the physician's global evaluation (according to a scoring
      system of 1 to 5), the Bath Ankylosing Spondilitis Disease Activity Index
      (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Dougados
      Functional Index (DFI), tragus-wall distance, chest expansion, modified Shober
      test (MST), fingertip-fibula head distance, and Nottingham Health Profile (NHP).
      RESULTS: Evaluations were completed in 54 patients in the two groups. Comparison
      of the groups showed significantly superior results for Group I for parameters of
      BASDAI, NHP total, pain, physical activity, tiredness and sleep score, patient's
      global evaluation and the physician's global evaluation at 3 weeks, but only for
      the parameters of patient's global evaluation and MST at 24 weeks. CONCLUSION:
      Balneotherapy has a supplementary effect on improvement in disease activity and
      functional parameters in AS patients immediately after the treatment period.
      However, in the light of our medium-term evaluation results, we suggest that
      further research is needed to assess the role of balneotherapy applied for longer
      durations in AS patients.

PMID- 16882593
TI  - Anti-centromere antibodies in patients with systemic lupus erythematosus.
AB  - BACKGROUND: Anti-centromere autoantibodies (ACA) are frequently detected in
      systemic sclerosis (SScl), especially in the calcinosis, Raynaud phenomenon,
      esophageal dysmotility, sclerodactyly, telangiectasia (CREST) syndrome, in which
      a prevalence of 55% has been reported. The presence of ACA in systemic lupus
      erythematosus (SLE) is so rare that its detection can raise serious doubts about
      the validity of the diagnosis. OBJECTIVE: To determine the frequency of ACA
      positive subjects from a wide monocentric cohort of SLE patients and analyse the
      clinical and biological characteristics of this group. METHODS: Five hundred and
      sixty consecutive SLE patients were systematically analysed for the presence of
      ACA and other autoantibodies using indirect immunofluorescence, counter
      immunoelectrophoresis, double immunodiffusion, enzyme-linked immunosorbent assay
      (ELISA), and Western-blot. RESULTS: ACA were detected in 11 SLE patients (1.9%);
      all of them were women. The CENP-B-specific ELISA was positive in all patients.
      The main clinical features of scleroderma (cutaneous sclerosis, sclerodactylia,
      digital ulcers, or pulmonary fibrosis) were not present in these patients, who
      did not differ clinically from the whole SLE group. CONCLUSIONS: ACA can be
      detected in patients with genuine SLE without concurrent scleroderma. Therefore,
      the presence of this antibody does not preclude the possibility of the diagnosis
      of SLE. In addition, SLE patients with ACA do not represent a different clinical
      subgroup.

PMID- 16882594
TI  - Random number generation evaluation in patients with systemic lupus erythematosus
      indicates a heterogeneous nature of central nervous system vulnerability.
AB  - OBJECTIVE: To evaluate the vulnerability of the central nervous system (CNS) in
      patients with systemic lupus erythematosus (SLE). METHODS: Forty-eight patients
      with SLE, 58 with schizophrenia in remission and 39 healthy controls were
      enrolled in the study. Patients vocally generated 100 numbers in a random
      fashion, using numbers 0 to 9, and were evaluated with seriality scores. Patients
      with SLE were subgrouped according to differences in the presence of Raynaud's
      phenomenon, anti-phospholipid antibody, lupus activity, and a history of
      neuropsychiatric (NP) lupus, and these patients were also evaluated by comparison
      with their counterparts. RESULTS: In general, patients with SLE showed lower
      seriality scores than patients with schizophrenia, and higher seriality scores
      than normal controls. The scores of the patients with a history of NP lupus
      matched those with schizophrenia, and the scores of never having NP lupus matched
      those of the healthy controls. CONCLUSIONS: CNS vulnerability may be prolonged in
      patients who have a history of NP lupus even when they appear to be in normal NP
      status. The damage in random number generation (RNG) observed in patients with a
      history of NP lupus seemed equal to that found in those with schizophrenia,
      whereas those patients never having NP lupus appeared to be equal to the
      controls. The current study suggests a heterogeneous nature of SLE and prolonged
      damage, especially in CNS vulnerability, when evaluating with RNG.

PMID- 16882595
TI  - Regulatory T cells in peripheral blood of patients with mixed connective tissue
      disease.
AB  - OBJECTIVE: To determine the percentage and absolute number of CD4+ regulatory T
      cells (Treg) in 48 patients with mixed connective tissue disease (MCTD). METHODS:
      Data were classified on the basis of the stage of the disease: 17 patients were
      in the active stage and 31 in the inactive stage. The absolute number of
      CD4+/intracellular interleukin-10+ (IL-10+) and CD4+CD25+high Treg cells was
      determined by flow cytometry. The percentage of CD4+CD25+high suppressor T-cells
      was determined on the basis of Foxp3 expression. RESULTS: The percentage and the
      absolute number of CD4+CD25+high Treg cells were lower in patients than in
      healthy controls (p<0.04), and were further decreased in patients with active
      MCTD and were lower than in the inactive stage (p<0.01). There was an increase in
      the percentage and absolute number of CD4+IL-10+ Treg cells in patients with MCTD
      compared to the healthy controls (p<0.02). The percentage of CD4+IL-10+ Treg
      cells was higher in the active stage of MCTD than in the inactive stage of the
      disease (p<0.005). However, we did not find any significant difference in the
      absolute number of CD4+IL-10+ Treg cells between the patients in the active and
      inactive stages of MCTD. CONCLUSION: Our results suggest that the decrease in the
      number of CD4+CD25+high Treg cells in an important factor in the immunoregulatory
      disturbance in patients with MCTD. We suggest that the increase in the number of
      CD4+IL-10+ Treg cells is a compensatory mechanism aiming to restore the balance
      between type 1 and type 2 cytokines in MCTD.

PMID- 16882596
TI  - Effects of low-intensity ultrasound (LIUS) stimulation on human cartilage
      explants.
AB  - OBJECTIVE: To evaluate the effects of low-intensity ultrasound (LIUS) stimulation
      on the anabolic state of human cartilage from patients with osteoarthritis (OA).
      METHODS: Explant cultures of human OA cartilage were stimulated for 10 min every
      day for 7 consecutive days using continuous-wave sonication at a frequency of 1
      MHz with spatial and temporal average intensities of 0 (control), 40, 200, 500,
      or 700 mW/cm2. The effects of LIUS on cell proliferation were evaluated by 3H
      thymidine incorporation. Proteoglycan synthesis was evaluated by the
      incorporation of 35S-sulfate and by Safaranin O staining. Collagen synthesis was
      evaluated by 3H-proline incorporation and immunohistochemistry. RESULTS: At an
      intensity of 200 mW/cm2, LIUS treatment induced the expression of collagen type
      II and proteoglycan measured by the incorporation of radioactivity and specific
      staining of the cartilage explants. However, the expression decreased again at
      the higher intensities of 500 or 700 mW/cm2. Ultrasound had no stimulatory effect
      on cell proliferation at any intensity. CONCLUSION: LIUS has anabolic effects on
      human cartilage in explant cultures, indicating a potentially important method
      for the repair of osteoarthritic cartilage.

PMID- 16882597
TI  - Determination of markers for collagen type I turnover in peritendinous human
      tissue by microdialysis: effect of catheter types and insertion trauma.
AB  - OBJECTIVES: Previous results from our group have shown that loading of human
      tendon elevates tendinous type I collagen production measured by microdialysis.
      However, exclusion of the observed elevation as a response to trauma from
      inserting the microdialysis catheters or a possible influence from the collagen
      production in skin was not determined. METHODS: Using the microdialysis method we
      measured the tissue levels of type I collagen metabolism markers [procollagen I
      COOH-terminal propeptide (PICP) and COOH-terminal telopeptide of type I collagen
      (ICTP)] in peritendinous tissue of the Achilles tendon in volunteers at two time
      points, 0 and 72 h. Using two different catheter types, an investigation of the
      contribution from the skin in the collagen results obtained was also examined.
      RESULTS: The data showed no significant changes in the dialysate levels for PICP
      or ICTP (p>0.05) in either of the catheters. CONCLUSION: Inserting microdialysis
      fibres around the Achilles tendon twice does not increase the collagen type I
      metabolism determined 3 days after the initial trauma, and when using
      microdialysis for measuring peritendinous collagen turnover the skin contribution
      can be regarded as negligible. These findings support microdialysis as a valid
      method for the determination of collagen metabolism in peritendinous tissue.

PMID- 16882598
TI  - The effect of TNFalpha blockade in complicated, refractory Kawasaki disease.
AB  - In Kawasaki disease (KD), a systemic vasculitis of childhood, serum levels of
      proinflammatory cytokines such as tumour necrosis factor alpha (TNFalpha) are
      elevated during the acute phase of the disease. Although the majority of children
      recover completely from a single dose of intravenous immunoglobulin (IVIG), the
      treatment is not always effective. In refractory cases of KD there are no
      documented treatment guidelines. A future role of biological agents directed
      against proinflammatory cytokines has recently been suggested by the American
      Heart Association (AHA). We describe two infants with severe KD, complicated by
      coronary as well as extracoronary aneurysms, who responded neither to repeated
      treatment with IVIG plus aspirin nor to corticosteroids. The children were
      subsequently treated with infliximab. In both cases, the effect was prompt and
      long-lasting. Clinical improvement was seen within a few days after the first
      dose, and regression of the aneurysms occurred within weeks.

PMID- 16882599
TI  - Demyelinating disease and cutaneous lymphocitic vasculitis after etanercept
      therapy in a patient with rheumatoid arthritis.

PMID- 16882600
TI  - Successful treatment of Sjogren's syndrome with rituximab.

PMID- 16882601
TI  - Pulmonary involvement starts in early stage ankylosing spondylitis.

PMID- 16882602
TI  - No additional steroid-sparing effect of cyclosporine A in giant cell arteritis.

PMID- 16882603
TI  - Myocarditis in adult-onset Still's disease despite significant immunosuppressive
      therapy.

PMID- 16882605
TI  - Ultra-rapid preparation of total genomic DNA from isolates of yeast and mould
      using Whatman FTA filter paper technology - a reusable DNA archiving system.
AB  - Conventional methods for purifying PCR-grade fungal genomic DNA typically require
      cell disruption (either physical or enzymatic) coupled with laborious organic
      extraction and precipitation stages, or expensive column-based technologies. Here
      we present an easy and extremely rapid method of preparing yeast and mould
      genomic DNAs from living cultures using Whatman FTA filter matrix technology.
      Aqueous suspensions of yeast cells or hyphal fragments and conidia (in the case
      of moulds) are applied directly (or after freeze-thawing) to dry FTA filters.
      Inoculated filters are then subjected to brief microwave treatment, to dry the
      filters and inactivate the organisms. Filter punches are removed, washed rapidly,
      dried and placed directly into PCR reactions. We show that this procedure
      inactivated all of the 38 yeast and 75 mould species tested, and generated PCR
      grade DNA preparations in around 15 minutes. A total of 218 out of 226 fungal
      isolates tested liberated amplifiable DNA after application to FTA filters.
      Detection limits with yeast cultures were approximately 10 colony-forming units
      per punch. Moreover, we demonstrate that filter punches can be recovered after
      PCR, washed and used in fresh PCR reactions without detectable cross
      contamination. Whatman FTA technology thus represents a cheap, ultra-rapid method
      of fungal genomic DNA preparation, and also potentially represents a powerful
      fungal DNA archiving and storage system.

PMID- 16882606
TI  - Cytokeratin expression in pseudoepitheliomatous hyperplasia of oral
      paracoccidioidomycosis.
AB  - Paracoccidioidomycosis (Pmycosis) is one the most prevalent deep systemic mycoses
      in Latin America. It is characterized by granulomatous inflammation and
      pseudoepitheliomatous hyperplasia. Cytokeratins (CKs) are a group of intermediate
      filaments of epithelial cells and their expression varies according to the
      epithelium type, differentiation and pathological processes. This study describes
      cytokeratin expression as examined by immunohistochemistry, in 28 cases of oral
      Pmycosis involving the buccal mucosa, lip, gingiva and hard palate. Expression of
      CKs in the basal layer of the epithelium in pseudoepitheliomatous hyperplasia of
      Pmycosis was similar to that in normal oral mucosa (NOM), but in Pmycosis CK1 and
      CK10 were not expressed in the spinous and superficial layers of the lip, gingiva
      or hard palate, and, in the spinous and superficial layers of the lip and buccal
      mucosa, CK14 was positive in contrast to NOM where it was negative. In Pmycosis,
      CK6 was more frequently expressed in the spinous layer of the lip, gingiva and
      hard palate, but nevertheless CK16 expression was decreased in the spinous and
      superficial layers of the gingiva and hard palate. We conclude that
      pseudoepitheliomatous hyperplasia in oral Pmycosis shows a different pattern of
      CK expression, particularly CKs 1, 10 and 14, compared with NOM.

PMID- 16882607
TI  - Comparison of multilocus sequence typing and Ca3 fingerprinting for molecular
      subtyping epidemiologically-related clinical isolates of Candida albicans.
AB  - Southern hybridization with the complex probe Ca3 is a well established tool for
      molecular subtyping of Candida albicans. Multilocus sequence typing (MLST) is a
      DNA sequence-based subtyping method recently applied to C. albicans and shown to
      have a high degree of intraspecies discriminatory power. However, its utility for
      studying the molecular epidemiology of sequential isolates from recurrent disease
      has not been established. We compared Ca3 Southern hybridization and MLST using
      seven housekeeping genes (CaAAT1a, CaACC1, CaADP1, CaPMI, CaSYA1, CaVPS13,
      CaZWF1b) for their ability to discriminate among 37 C. albicans isolates from
      recurrent cases of oropharyngeal candidiasis (OPC) in ten HIV-positive patients
      from India and the US. Among the 37 isolates, MLST identified 23 distinct
      genotypes (index of diversity = 97%); Ca3 Southern hybridization identified 21
      distinct genotypes (index of diversity = 95%). Both methods clustered isolates
      into seven genetically-related groups and, with one exception, isolates that were
      indistinguishable by MLST were indistinguishable or highly related by Ca3
      Southern hybridization. These results demonstrate that MLST performs equally well
      or better compared to Ca3 Southern hybridization for defining genetic-relatedness
      of sequential C. albicans isolates from recurrent cases of OPC in HIV-positive
      patients.

PMID- 16882608
TI  - Patch test responses to Malassezia pachydermatis in healthy basset hounds and in
      basset hounds with Malassezia dermatitis.
AB  - The effects of the patch test application of Malassezia pachydermatis extracts
      were evaluated in seven healthy basset hounds and in seven basset hounds with
      Malassezia dermatitis. Antigens (4 and 0.4 mg/ml) and saline controls were
      applied for 48 h using filter paper discs in Finn chambers. One healthy basset
      hound and five affected hounds showed positive patch test reactivity to the yeast
      antigens. Positive patch test reactions were characterized histologically by mild
      epidermal hyperplasia and mild to moderate perivascular, periadnexal and
      interstitial infiltrates of neutrophils and CD3+ lymphocytes. Immediate
      intradermal test reactivity to M. pachydermatis antigens was seen in one healthy
      and one affected hound, whereas delayed intradermal test reactivity was seen in
      six healthy hounds and five affected hounds. This study indicates that patch test
      reactivity to M. pachydermatis antigen may occur in healthy basset hounds, and in
      contrast to delayed intradermal test reactivity, is more frequent in basset
      hounds with Malassezia dermatitis.

PMID- 16882609
TI  - Relationship between metabolism and biomass of medically important zygomycetes.
AB  - Little is known about the relationships between metabolic activity and fungal
      biomass or time of incubation for medically important fungal pathogens.
      Understanding these relationships may be especially relevant for rapidly growing
      organisms, such as zygomycetes. A range of inocula of five clinical isolates of
      zygomycetes (one each of Rhizopus oryzae,Rhizopus microsporus, Cunninghamella
      bertholletiae, Mucor circinelloides and Absidia corymbifera) were incubated for
      6, 8, 12, 24 and 48 h, after which hyphal mass was assessed
      spectrophotometrically and metabolic activity was measured using various
      concentrations of XTT and menadione. Both linear regression and the Boltzmann
      sigmoid model were used and compared for description of relationships between
      metabolic activity, biomass and time of incubation. Modeling was further applied
      to eleven additional zygomycete isolates. The relationships of biomass or
      metabolic activity as a function of time of incubation were well described with
      the Boltzmann sigmoid model. The latter was superior to linear regression in
      describing the relationship between metabolic activity and fungal biomass. For
      all isolates of zygomycetes, increases in metabolic activity preceded increases
      in biomass. Inter-species differences in growth patterns were observed, with
      Rhizopus microsporus and Mucor spp. reaching the plateau of growth earlier
      compared to other species. These findings on the temporal relationship and inter
      species differences of hyphal growth and metabolic activity for zygomycetes may
      be useful in the design and interpretation of in vitro studies of these emerging
      pathogens.

PMID- 16882610
TI  - Susceptibility pattern among pathogenic species of Aspergillus to physical and
      chemical treatments.
AB  - Physical treatments, like heating or irradiation, may reduce the viability or
      eradicate Aspergillus conidia, which in turn might help to prevent infections by
      members of this genus. Chemical treatments can also prevent infection resulting
      from contaminated hospital fabrics or surfaces. Our objectives were to study the
      kinetics of survival of the conidia of pathogenic Aspergillus species, like A.
      fumigatus, A. flavus and A. niger, during exposure to heating at 60 degrees C and
      microwave irradiation. In addition, we evaluated the susceptibility patterns of
      Aspergillus conidia to such chemical agents as cupric sulphate and sodium
      hypochlorite. Heating the conidia of A. flavus and A. niger at 60 degrees C for
      45 min was found to be fungicidal (reduction > 104 conidia/ml), but was not with
      A. fumigatus conidia. Short periods of microwave irradiation (40 s) resulted in a
      significant reduction of the viability of the conidia of these three Aspergillus
      species as a result of lethal membrane lesions. All Aspergillus species were
      similarly susceptible to cupric sulphate and sodium hypochlorite. Therefore,
      heating, microwave and the chemical treatments tested impaired significantly the
      viability of Aspergillus conidia, supporting the use of these methods as
      preventive measures among patients at risk.

PMID- 16882611
TI  - Late-onset invasive aspergillosis in organ transplant recipients in the current
      era.
AB  - We assessed predictive factors and characteristics of patients with late-onset
      invasive aspergillosis in the current era of novel immunosuppressive agents.
      Forty transplant recipients with invasive aspergillosis were included in this
      prospective, observational study initiated in 2003 at our institutions. In 50%
      (20/40) of these patients, the infections were late-occurring. Receipt of
      sirolimus in conjunction with tacrolimus for refractory rejection or cardiac
      allograft vasculopathy (P=0.047) was significantly associated with late-onset
      infection. The use of depleting or non-depleting T or B-cell antibodies, either
      as induction or as antirejection therapy did not correlate with time to onset of
      invasive aspergillosis. Mortality at 90 days was 20% (4/20) for the patients with
      early-onset infection and 45% (9/20) for those with late-onset infection
      (P=0.17). Thus, nearly one-half of the Aspergillus infections in transplant
      recipients in the current era are late-occurring. These data have implications
      relevant for prophylactic strategies and guiding clinical management of
      transplant recipients presenting with pulmonary infiltrates.

PMID- 16882612
TI  - Arthroderma olidum, sp. nov. A new addition to the Trichophyton terrestre
      complex.
AB  - In 1981, four fungal isolates from hair of the European badger (Meles meles) were
      examined by Dr Phyllis Stockdale at the Commonwealth Mycological Institute, Kew,
      and deposited in the UK National Collection of Pathogenic Fungi as an undescribed
      member of the Trichophyton terrestre complex. The present paper formalizes the
      complete description of a new ascomycete taxon, Arthroderma olidum following
      successful recent attempts to re-isolate the same fungus from the soil of Badger
      holes in South West England. Furthermore, using ribosomal RNA gene sequencing, we
      show that the asexual form of A. olidum is conspecific with the recently
      described Trichophyton eboreum1 isolated from a human skin specimen in Germany.

PMID- 16882613
TI  - Primary renal zygomycosis due to Rhizopus oryzae.
AB  - Primary renal zygomycosis is a rare fungal infection, and only 45 cases have been
      reported in the literature. The major etiologic agents of the disease were Mucor
      spp., Rhizomucor spp., Rhizopus spp. and Absidia spp. Here we report a case of
      primary renal zygomycosis due to Rhizopus oryzae infection. The patient had
      systemic lupus erythematosus and was treated with corticosteroids. He had
      frequent micturition, urodynia and passed amorphous and membranous-looking masses
      through the urethra several times prior to admission. Histopathological
      examination of the mass showed numerous broad and nonseptate hyphae. Rhizopus
      oryzae was isolated from the mass. We also reviewed the clinical features of
      primary renal zygomycosis in the literature.

PMID- 16882614
TI  - Chromoblastomycosis in children and adolescents in the endemic area of the Falcon
      State, Venezuela.
AB  - The present paper describes 22 cases of chromoblastomycosis (CBM) caused by
      Cladophialophora carrionii in children and adolescents (2-19 years old). The
      patients were seen between 1992 and 2004 and all resided in a CBM endemic area in
      the semi-arid zone of the Falcon state, Venezuela. Twelve of the 22 patients
      (54.55%) had close relatives who also had CBM and 19 (86.36%) were male. Lesions
      consisted of erythematous papules with desquamation or squamous plaques (0.12
      14.19 cm in diameter), located primarily on the upper limbs (77.27% of patients).
      Thirteen of the patients were treated with topical 5-fluorouracil (5-FU; 1%
      cream), seven with topical ajoene (0.5% gel) and two had electrodesiccation
      and/or fulguration. Two patients who did not respond to 5-FU were treated with
      oral itraconazole (100 mg/day for 1 month). Complete clinical and mycological
      remission was achieved in 17/20 (85%) of the patients treated with 5-FC, ajoene
      and electrodesiccation and/or fulguration. In addition, similar results were
      obtained with the two patients who received itraconazole therapy. These cases
      emphasize the importance of early diagnosis in difficult-to-treat mycotic
      diseases such as CBM. By early intervention we were able to employ topical
      treatment with a minimum of adverse effects to achieve a high percentage of
      favorable therapeutic responses. The patients were thus able to avoid the
      evolution of the chronic, deforming and incapacitation clinical manifestations
      associated with CBM.

PMID- 16882615
TI  - Lethal brain abscess due to the fungus Scedosporium apiospermum (teleomorph
      Pseudallescheria boydii) after a near-drowning incident: case report and review
      of the literature.
AB  - A 39-year-old healthy man developed a brain abscess weeks after a near-drowning
      incident. Scedosporium apiospermum, the anamorph of Pseudallescheria boydii, was
      isolated from the abscess. The patient died 153 days after the accident despite
      antifungal therapy. We discuss the role of antifungals and review the literature
      for comparable cases.

PMID- 16882617
TI  - Organ culture studies on the development of mouse embryo limb buds under EMF
      influence.
AB  - PURPOSE: To investigate the effects of an electromagnetic field (EMF) on limb bud
      development in vitro, an organ culture system was applied. MATERIALS AND METHODS:
      Three test groups of amputated mouse limb buds included the experimental (E)
      group which received EMF (50 Hz/13.1 mT, for 2 h), a sham (Sh) group exposed to
      no EMF treatment and the control (C) group. The limb buds of E and Sh groups (n =
      20 per group) were amputated from mouse embryos on day 11.5 of development and
      cultured in minimum essential medium Eagle (MEM Eagle), supplemented with 15%
      human embryo cord serum, for 2 days, while those of group C (n = 20) were removed
      on day 13.5 of development. All samples were fixed in Bouin's fluid, embedded in
      paraffin, serially sectioned (5 microm thick) and stained with Hematoxylin and
      Eosin. Limb bud measurements were performed using a scaled graticule. RESULTS:
      Morphological and histological examinations showed significant changes in the
      experimental limb bud group as compared with the sham and control groups. The
      growth rate in both fore and hindlimb buds in proximal-distal (P-D) and anterior
      posterior (A-P) axes were significantly increased. Chondrocyte counts and mitotic
      figures of mesenchymal and red blood cells were significantly increased as
      compared with those of sham and control groups. There was also a significant
      reduction of mesenchymal cell counts, while no significant difference was
      observed in the degenerated cell counts among the three groups. CONCLUSIONS:
      These findings suggest that EMF, under the conditions applied, has progressive
      effects on the limb bud development and that both proliferation and
      differentiation can be stimulated in vitro.

PMID- 16882616
TI  - Nosocomial infection in newborns by Pichia anomala in a Brazilian intensive care
      unit.
AB  - Disseminated candidiasis is the most common nosocomial fungal infection, and
      Candida albicans has been reported to account for 50% to more than 70% of cases
      of invasive candidiasis. However, recent reports have also suggested the
      emergence of infections caused by non-albicans species. In addition, less-common
      pathogenic yeasts (Malassezia, Trichosporon, Rhodotorula, Debaryomyces and
      Pichia) have recently been reported, with increased frequency, as causes of
      nosocomial infections with high mortality. This article describes two cases of
      fungemia caused by Pichia anomala in newborns that occurred in an intensive care
      unit (ICU), in November 2004 at the Instituto da Crianca (Pediatric Institute) of
      the Hospital das Clinicas of the School of Medicine, Sao Paulo University,
      Brazil. The principal factors related to virulence (proteinase and phospholipase)
      and the susceptibility of the isolated strains to antifungal agents were also
      evaluated, and the biotype of each strain was determined through the use of an
      epidemiological marker (killer biotype).

PMID- 16882618
TI  - Scalp localization of human auditory cortical activity modified by GSM
      electromagnetic fields.
AB  - PURPOSE: This study attempted to determine whether there is a localized effect of
      GSM (Global System for Mobile communications) microwaves by studying the Auditory
      Evoked Potentials (AEP) recorded at the scalp of nine healthy subjects and six
      epileptic patients. MATERIALS AND METHODS: We determined the influence of GSM
      RadioFrequency (RF) on parameters characterizing the AEP in time or/and frequency
      domains. A parameter selection method using SVM (Support Vector Machines)-based
      criteria allowed us to estimate those most altered by the radiofrequencies. The
      topography of the parameter modifications was computed to determine the
      localization of the radiofrequency influence. A statistical test was conducted
      for selected scalp areas, in order to determine whether there were significant
      localized alterations due to the RF. RESULTS: The epileptic patients showed a
      lengthening of the scalp component N100 (100 ms latency) in the frontal area
      contralateral to the radiation, which may be due to an afferent tract alteration.
      For the healthy subjects, an amplitude increase of the P200 wave (200 ms latency)
      was identified in the frontal area. CONCLUSIONS: The present study suggests that
      radiofrequency fields emitted by mobile phones modify the AEP. Nevertheless, no
      direct link between these findings and RF-induced damages in brain function was
      established.

PMID- 16882619
TI  - Linear energy transfer dependence of the effects of carbon ion beams on
      adventitious shoot regeneration from in vitro leaf explants of Saintpaulia
      ionahta.
AB  - PURPOSE: To determine the effects of carbon ion beams with five different linear
      energy transfer (LET) values on adventitious shoots from in vitro leaf explants
      of Saintpaulia ionahta Mauve cultivar with regard to tissue increase, shoots
      differentiation and morphology changes in the shoots. MATERIALS AND METHODS: In
      vitro leaf explant samples were irradiated with carbon ion beams with LET values
      in the range of 31 approximately 151 keV/microm or 8 MeV of X-rays (LET = 0.2
      keV/microm) at different doses. Fresh weight increase, surviving fraction and
      percentage of the explants with regenerated malformed shoots in all the
      irradiated leaf explants were statistically analysed. RESULTS: The fresh weight
      increase (FWI) and surviving fraction (SF) decreased dramatically with increasing
      LET at the same doses. In addition, malformed shoots, including curliness,
      carnification, nicks and chlorophyll deficiency, occurred in both carbon ion beam
      and X-ray irradiations. The induction frequency with the former, however, was far
      more than that with the X-rays. CONCLUSIONS: This work demonstrated the LET
      dependence of the relative biological effectiveness (RBE) of tissue culture of
      Saintpaulia ionahta according to 50% FWI and 50% SF. After irradiating leaf
      explants with 5 Gy of a 221 MeV carbon ion beam having a LET value of 96
      keV/microm throughout the sample, a chlorophyll-deficient (CD) mutant, which
      could transmit the character of chlorophyll deficiency to its progeny through
      three continuous tissue culture cycles, and plantlets with other malformations
      were obtained.

PMID- 16882620
TI  - Investigation of new cytogenetic biomarkers specific to high-LET radiation using
      in vivo and in vitro exposed human lymphocytes.
AB  - PURPOSE: To find detectable cytogenetic biomarkers that can offer information
      about the radiation quality of in vivo exposure retrospectively. MATERIALS AND
      METHODS: Chromosome-type aberrations of peripheral lymphocytes of uterine cancer
      patients that received internal gamma- and external X-ray therapy or carbon beam
      therapy and of victims severely exposed to neutrons and gamma-rays in a
      criticality accident that occurred in Tokai-mura, Japan were analysed. Data
      obtained from in vitro irradiation experiments using 60Co gamma-rays and 10 MeV
      neutrons were compared with the in vivo exposure data. RESULTS: The ratio of
      acentric rings to dicentric chromosomes (termed RaD ratio) and that of excess
      fragments to dicentrics (termed EfD ratio) showed significant (p < 0.05)
      differences between the two groups of cancer patients, and these ratios for
      accidental victims were in between the values of the two groups of cancer
      patients. The in vitro studies using doses equivalent to 1 - 3 Gy of gamma-rays
      have confirmed that the EfD ratios were increased with the high LET (linear
      energy transfer) and RaD ratios decreased. CONCLUSION: The present data show that
      the RaD and EfD ratios can be used as cytogenetic biomarkers of exposure to high
      LET radiation at least within a few years of exposure.

PMID- 16882621
TI  - Follow-up of stable chromosomal aberrations in gamma-ray irradiated non-human
      primates.
AB  - PURPOSE: The purpose of this study was to examine a new approach to retrospective
      biological dosimetry, by using a long-term animal model to determine the
      stability of translocation frequency after in vivo irradiation. While the
      frequency of dicentrics is known to decrease over time, the persistence of more
      stable chromosomal aberrations such as translocations could be useful if their
      stability were definitively proved. MATERIALS AND METHODS: Four monkeys (Macaca
      fascicularis) were exposed to two different doses of ionizing radiation: 2 Gy
      whole body irradiation for two and 4 Gy for two others. Blood samples were
      obtained at various times after irradiation. Both total and two-way
      translocations were detected by fluorescence in situ hybridization.
      Translocations were scored in stable cells, that is, those without dicentrics,
      rings or fragments. The course of translocation frequency was analysed at four
      time-points: one hour (H1), 2 months (M2), 10 months (M10) and 31 months (M31)
      after irradiation. RESULTS: We observed two separate trends in translocation
      frequency: Total translocation frequency decreased slightly in animals irradiated
      with a dose of 2 Gy, while two-way translocation frequency was relatively stable
      in all irradiated animals. CONCLUSIONS: We confirmed the long-term stability of
      translocations and found that it seems to depend on the type of the translocation
      recorded. Overall translocations were stable for up to 31 months regardless of
      dose, but two-way translocations were more stable than those that were non
      reciprocal, especially in stable cells.

PMID- 16882622
TI  - Increased excretion of collagen crosslinks in irradiated patients indicates
      destruction of collagen.
AB  - PURPOSE: In a recent study we showed an instant radiogenic destruction of
      collagen in dental tissues. The hypothesis of this analysis was that there is a
      destruction of collagen directly in bone during irradiation. Our intention was to
      prove this assumption by the analysis of the intraindividual progression of
      urinary excretion of bone specific collagen crosslinks before, during and after
      radiotherapy (RT) of secondary malignant bone tumors. MATERIAL AND METHODS: Forty
      six patients were irradiated with a mean dose of 32 Gy (range 30 - 46 Gy). Four
      urine probes were collected from each patient before, during, at the end and 6 -
      8 weeks after RT. Measurement of the mature collagen crosslinks
      hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP) was performed by high
      performance liquid chromatography (HPLC). RESULTS: In 43 patients we found
      increasing HP and LP concentrations by comparing the different chosen time
      points. As regards to HP the urine excretion was significantly increased at the
      end (p = 0.02) and six weeks after RT (p = 0.01) and for LP six weeks after RT (p
      = 0.01). We observed significantly higher urinary HP levels in patients treated
      with doses of 35 - 46 Gy as compared to patients treated with 30 Gy (p = 0.05).
      CONCLUSIONS: The urinary excretion of HP and LP was increased directly after a
      course of RT. This finding may reflect either destruction of collagen or
      increased bone remodeling/resorption after radiotherapy. Either way these
      findings suggest a relation to the mechanical instability of bone directly after
      radiotherapy. Future investigations of irradiated patients without osseous
      metastases will further clarify this matter.

PMID- 16882623
TI  - Microarray analysis of differentially expressed genes in mouse bone marrow
      tissues after ionizing radiation.
AB  - PURPOSE: To identify differentially expressed genes in mouse bone marrow involved
      in radiation-induced injury. MATERIALS AND METHODS: Microarray analysis was used
      to identify the differentially expressed genes and other techniques, e.g.,
      polymerase chain reaction (PCR), western-blotting and antisense were also used to
      validate the results. RESULTS: DNA microarray analysis demonstrated that the mRNA
      of 34 genes increased and 69 genes decreased in mouse bone marrow cells (BMC)
      from C57BL mice 6 h after a whole body dose of 6.5 Gy. These differentially
      expressed genes were involved in a number of processes including DNA
      replication/repair, proliferation/apoptosis, cell cycle control and RNA
      processing. In these experiments, a decline of the mammalian homolog Sir2a (an
      acronym for the silent mating type information regulation 2 homolog [SIRT1]) mRNA
      accompanied by an increase of P53 protein acetylation was observed in irradiated
      BMC. To determine whether the reduced SIRT1 is related to the higher acetylation
      status of P53 after irradiation, we designed and synthesized antisense
      oligonucleotides (AS) targeting human SIRT1 mRNA. Notably, AS transfection
      increased tumor protein 53 (P53) protein acetylation and bax-luciferase activity
      in human bone marrow stromal cell line (HS-5) after radiation. Furthermore, the
      AS transfer stimulated cell apoptosis in post-irradiation HS-5 cells. CONCLUSION:
      Ionizing radiation (IR) affects the expression of a series of genes including
      genes involved in G1/S transition and the P53 pathway. Among those, reduction of
      SIRT1 was seen to be involved in transactivation of P53.

PMID- 16882625
TI  - Physical activity for health.

PMID- 16882626
TI  - Agility literature review: classifications, training and testing.
AB  - At present, no agreement on a precise definition of agility within the sports
      science community exists. The term is applied to a broad range of sport contexts,
      but with such great inconsistency, it further complicates our understanding of
      what trainable components may enhance agility. A new definition of agility is
      proposed: "a rapid whole-body movement with change of velocity or direction in
      response to a stimulus". Agility has relationships with trainable physical
      qualities such as strength, power and technique, as well as cognitive components
      such as visual-scanning techniques, visual-scanning speed and anticipation.
      Agility testing is generally confined to tests of physical components such as
      change of direction speed, or cognitive components such as anticipation and
      pattern recognition. New tests of agility that combine physical and cognitive
      measures are encouraged.

PMID- 16882627
TI  - Late information pick-up is preferred in basketball jump shooting.
AB  - In this study we examined the timing of optical information pick-up in basketball
      jump shooting using an intermittent viewing technique. We expected shooters to
      prefer to look at the basket as late as possible under the shooting style used.
      Seven experts with a high shooting style and five experts with a low shooting
      style took 50 jump shots while wearing liquid-crystal glasses that opened and
      closed at pre-set intervals. In principle, under this constraint, the
      participants could control when they saw the basket by actively modulating the
      timing of their movements. Analyses of the phasing of the movements relative to
      the events defined on the glasses revealed that low-style shooters preferred to
      see the basket just before the ball passed their line of sight, whereas high
      style shooters tended to view the basket from underneath the ball after it passed
      their line of sight. Thus, most shooters preferred to pick up optical information
      as late as possible given the adopted shooting style. We conclude that, in
      dynamic far aiming tasks such as basketball jump shooting, late pick-up of
      optical information is critical for the successful guidance of movements.

PMID- 16882628
TI  - Effects of sensory-level high-volt pulsed electrical current ondelayed-onset
      muscle soreness.
AB  - Ten healthy males and ten healthy females aged 21.5 +/- 3.2 years (mean +/- s)
      participated in the study, which was designed to evaluate the effectiveness of
      sensory level-high volt pulsed electrical current (HVPC) on delayed-onset muscle
      soreness (DOMS). Arm discomfort, elbow extension range of motion and isometric
      elbow flexion strength were obtained as baseline measurements. Delayed-onset
      muscle soreness was induced in the participants' dominant or non-dominant arm
      using two sets of 20 maximal eccentric elbow flexion contractions. After the
      induction of DOMS, the participants were randomly divided into an experimental
      condition (HVPC) or a placebo condition. The experimental condition consisted of
      20 min of HVPC immediately after the induction of DOMS, and 20 min every 24 h for
      three consecutive days thereafter. The participants in the placebo condition
      received an intervention similar in design; however, no electrical current was
      administered. Baseline measurements were reevaluated at 24, 48, 72 and 96 h after
      the induction of DOMS. Three weeks later, the participants returned and the
      protocol was repeated on the contralateral limb, using the opposite intervention
      (HVPC or placebo). Repeated-measures analysis of variance revealed a significant
      increase in overall arm discomfort, decrease in elbow extension and decrease in
      isometric strength for both conditions over time. No significant main effect of
      treatment, or time-by-treatment interaction, was found for the HVPC condition
      when compared with the placebo condition for any variable. Sensory-level HVPC, as
      utilized in our application, was ineffective in reducing the measured variables
      associated with DOMS.

PMID- 16882629
TI  - The effect of muscle fatigue on instep kicking kinetics and kinematics in
      association football.
AB  - The aim of this study was to examine the effect of leg muscle fatigue on the
      kinetics and kinematics of the instep football kick. Fatigue was induced by
      repeated, loaded knee extension (40% body weight) and flexion (50% body weight)
      motions on a weight-training machine until exhaustion. The kicking motions of
      seven male players were captured three-dimensionally at 500 Hz before and
      immediately after the fatigue protocol. The significantly slower ball velocity
      observed in the fatigue condition was due to both reduced lower leg swing speed
      and poorer ball contact. The reduced leg swing speed, represented by a slower toe
      linear velocity immediately before ball impact and slower peak lower leg angular
      velocity, was most likely due to a significantly reduced resultant joint moment
      and motion-dependent interactive moment during kicking. These results suggest
      that the specific muscle fatigue induced in the present study not only diminished
      the ability to generate force, but also disturbed the effective action of the
      interactive moment leading to poorer inter-segmental coordination during kicking.
      Moreover, fatigue obscured the eccentric action of the knee flexors immediately
      before ball impact. This might increase the susceptibility to injury.

PMID- 16882630
TI  - Measurement of motivational imagery abilities in sport.
AB  - Athletes report using imagery most often to successfully cope with and master
      challenging situations. This function of imagery is termed "motivational general
      mastery" and includes imagining being focused, confident and in control in
      difficult circumstances. Also, athletes often use imagery to regulate their
      arousal levels (e.g. relaxing, psyching up) and this function of imagery is
      termed "motivational-general arousal". While most athletes report employing these
      two motivational functions of imagery, their ability to do so has not been
      examined. The aim of the present study was to develop a measure of motivational
      general sport imagery ability, the Motivational Imagery Ability Measure for Sport
      (MIAMS). This was accomplished through three phases. Across these phases,
      evidence was generated showing that the psychometric properties of the instrument
      are adequate. In addition, the relationship of scores on the MIAMS to demographic
      variables, including sex, sport type and competitive standard, were examined. It
      was found that athletes participating at a competitive level scored higher on the
      MIAMS than athletes participating at a recreational level.

PMID- 16882631
TI  - Effects of training on spleen and peritoneal exudate reactive oxygen species and
      lymphocyte proliferation by splenocytes at rest and after an acute bout of
      exercise.
AB  - The purpose of this study was to analyse the effect of regular exercise on spleen
      and peritoneal exudate reactive oxygen species (ROS) and lymphocyte proliferation
      by splenocytes. Twenty-four female BALB/c mice were randomly divided into trained
      (n = 12) and untrained (n = 12) groups. These two groups were further divided
      into mice that were studied at rest (trained/rest, n = 5; untrained/rest, n = 6)
      and immediately after a 2 h acute bout of exercise (trained/exercise, n = 6;
      untrained/exercise, n = 6). The animals were bred in the animal facility of the
      Yonsei University College of Medicine, where they were housed in a temperature-
      (22 - 24 degrees Celsius) and humidity- (50 - 60%) controlled environment, with a
      12 h photoperiod, and provided with food and water ad libitum. The trained mice
      underwent 10 weeks of endurance swimming training (5 days per week) in water at
      26 - 29 degrees Celsius for 60 min. Changes in body mass, proliferative activity
      and the production of reactive oxygen species from spleen lymphocytes and
      peritoneal exudate cells were determined. The splenic lymphocytes of the trained
      mice had much greater proliferative activity than those of the untrained mice (P
      < 0.05). Trained mice had lower ROS production in splenic lymphocytes and
      peritoneal exudate cells than untrained mice. In both groups, there was
      substantial inhibition of proliferative activity stimulated with medium,
      concanavalin A and lipopolysaccharide following the acute bout of exercise. This
      may have been caused by excessive ROS production following the acute exercise
      session.

PMID- 16882632
TI  - Food attitudes in female athletes: association with menstrual cycle length.
AB  - The aim of this study was to examine the relationship between indicators of risk
      of disordered eating, body image and varied menstrual cycle lengths. Altogether,
      151 female athletes were invited from 16 sports and 70 female non-athletic
      controls were recruited from a university lecture class. The participants
      completed several surveys, including demographics, menstrual cycle history,
      physical activity, Eating Disorder Inventory (EDI) and the Three Factor Eating
      Questionnaire (TFEQ). Selected EDI subscales were summed to reflect eating
      disorder risk and body image. Menstrual cyclicity was based on self-reported
      cycle length for the last 6 months (normal cycles = 26-32 days, irregular cycles
      < or =26 or >32 days). Athletes overall had more irregular cycles (29.1%) than
      the non-athletes (15.7%) (P < 0.05). There were significant differences in scores
      for eating disorder risk, body dissatisfaction, drive for thinness, cognitive
      restraint (TFEQ) and disinhibition (TFEQ), only when athletes were divided based
      on menstrual cyclicity (i.e. irregularly cycling athletes had higher scores than
      athletes with normal menstrual cycle lengths). No differences in these scores
      were found between non-athletes with normal or irregular menstrual cycle lengths.
      In conclusion, irregularly short or long menstrual cycle length is associated
      with subtle indications of higher risk of disordered eating in female athletes.

PMID- 16882633
TI  - The effect of a complex training and detraining programme on selected strength
      and power variables in early pubertal boys.
AB  - Complex training, a combination of resistance training and plyometrics is growing
      in popularity, despite limited support for its efficacy. In pre- and early
      pubertal children, the study of complex training has been limited, and to our
      knowledge an examination of its effect on anaerobic performance characteristics
      of the upper and lower body has not been undertaken. Furthermore, the effect of
      detraining after complex training requires clarification. The physical
      characteristics (mean+/-s) of the 54 male participants in the present study were
      as follows: age 12.3 +/- 0.3 years, height 1.57 +/- 0.07 m, body mass 50.3 +/-
      11.0 kg. Participants were randomly assigned to an experimental (n = 33) or
      control group (n = 21). The training, which was performed three times a week for
      12 weeks, included a combination of dynamic constant external resistance and
      plyometrics. After training, participants completed 12 weeks of detraining. At
      baseline, after training and after detraining, peak and mean anaerobic power,
      dynamic strength and athletic performance were assessed. Twenty-six participants
      completed the training and none reported any training-related injury. Complex
      training was associated with small increases (< or =5.5%) in peak and mean power
      during training, followed by decreases of a similar magnitude (< or = -5.9%)
      during detraining (P < 0.05). No changes or minor, progressive increases (< or
      =1.5%) were evident in the control group (P > 0.05). In the experimental group,
      dynamic strength was increased by 24.3 - 71.4% (dependent on muscle group; P <
      0.01), whereas growth-related changes in the control group varied from 0 to 4.4%
      (P > 0.05). For 40-m sprint running, basketball chest pass and vertical jump test
      performance, the experimental group saw a small improvement (< or =4.0%) after
      training followed by a decline (< or = -4.4%) towards baseline during detraining
      (P < 0.05), whereas the control group experienced no change (P > 0.05). In
      conclusion, in pre- and early pubertal boys, upper and lower body complex
      training is a time-effective and safe training modality that confers small
      improvements in anaerobic power and jumping, throwing and sprinting performance,
      and marked improvements in dynamic strength. However, after detraining, the
      benefits of complex training are lost at similar rates to other training
      modalities.

PMID- 16882634
TI  - Heat transfer variations of bicycle helmets.
AB  - Bicycle helmets exhibit complex structures so as to combine impact protection
      with ventilation. A quantitative experimental measure of the state of the art and
      variations therein is a first step towards establishing principles of bicycle
      helmet ventilation. A thermal headform mounted in a climate-regulated wind tunnel
      was used to study the ventilation efficiency of 24 bicycle helmets at two wind
      speeds. Flow visualization in a water tunnel with a second headform demonstrated
      the flow patterns involved. The influence of design details such as channel
      length and vent placement was studied, as well as the impact of hair. Differences
      in heat transfer among the helmets of up to 30% (scalp) and 10% (face) were
      observed, with the nude headform showing the highest values. On occasion, a
      negative role of some vents for forced convection was demonstrated. A weak
      correlation was found between the projected vent cross-section and heat transfer
      variations when changing the head tilt angle. A simple analytical model is
      introduced that facilitates the understanding of forced convection phenomena. A
      weak correlation between exposed scalp area and heat transfer was deduced. Adding
      a wig reduces the heat transfer by approximately a factor of 8 in the scalp
      region and up to one-third for the rest of the head for a selection of the best
      ventilated helmets. The results suggest that there is significant optimization
      potential within the basic helmet structure represented in modern bicycle
      helmets.

PMID- 16882635
TI  - Moderate-domain pulmonary oxygen uptake kinetics and endurance running
      performance.
AB  - The aims of this study were to determine if the primary time constant (tau) for
      oxygen uptake (VO2) at the onset of moderate-intensity treadmill exercise is
      related to endurance running performance, and to establish if tau could be
      considered a determinant of endurance running performance. Thirty-six endurance
      trained male runners performed a series of laboratory tests, on separate days, to
      determine maximal oxygen uptake (VO2max), the ventilatory threshold (VT) and
      running economy. In addition, runners completed six transitions from walking (4
      km x h-1) to moderate-intensity running (80% VT) for the determination of the VO2
      primary time constant and mean response time. During all tests, pulmonary gas
      exchange was measured breath-by-breath. Endurance running performance was
      determined using a treadmill 5-km time-trial, after which runners were considered
      as combined performers (n=36) and, using a ranking system, high performers (n=10)
      and low performers (n=10). Relationships between tau and endurance running
      performance were quantified using correlation coefficients (r). Stepwise multiple
      regression was used to determine the primary predictor variables of endurance
      running performance in combined performers. Moderate correlations were observed
      between tau, mean response time and endurance running performance, but only for
      the combined performers (r=-0.55, P=0.001 and r=-0.50, P=0.002, respectively).
      The regression model for predicting 5-km performance did not include tau or mean
      response time. The velocity at VO2max was strongly correlated to endurance
      running performance in all groups (r=0.72 - 0.84, P < 0.01) and contributed
      substantially to the prediction of performance. In conclusion, the results
      suggest that despite their role in determining the oxygen deficit and having a
      moderate relationship with endurance running performance, neither tau nor mean
      response time is a primary determinant of endurance running performance.

PMID- 16882636
TI  - Satisfaction with sexual life among persons with traumatic spinal cord injury and
      meningomyelocele.
AB  - PURPOSE: To study satisfaction with sexual life and self-assessed sufficiency of
      sexual counselling in persons with traumatic spinal cord injury (SCI) and
      meningomyelocele (MMC). METHOD: A postal questionnaire on aspects of health and
      functioning was answered by 190 persons with traumatic SCI who had been treated
      in the Spinal Injuries Unit in Sahlgrenska University Hospital, Goteborg, Sweden
      and 41 persons with MMC who were admitted to the Young Adult Teams in Goteborg,
      Boras and Skovde, Sweden. RESULTS: On a numerical scale from 0 (dissatisfied) to
      10 (satisfied) the median of satisfaction with sexual life was 3 for the men and
      4 for the women among the persons with traumatic SCI. In the MMC group the median
      of satisfaction with sexual life was 5 for the men and 8 for the women. Sexual
      dissatisfaction increased with increasing age in both groups. Inconvenience
      caused by urinary and faecal incontinence, as well as neuropathic pain increased
      sexual dissatisfaction in the men with traumatic SCI. A total of 69% of the men
      with traumatic SCI and 56-59% of the participants in other subgroups reported
      that the sexual counselling they had received was sufficient. CONCLUSIONS: The
      results corroborate findings from earlier studies that satisfaction with sexual
      life is rather low among persons with SCI. Especially ageing men with traumatic
      SCI who have sustained injury at an older age are a challenge for rehabilitation.
      The high satisfaction with sexual life in the women in comparison with the men
      with MMC is a finding not reported earlier. Our results suggest that adequate
      treatment of incontinence and pain might improve even sexual satisfaction. Sexual
      counselling should be given to all individuals with SCI and to their partners.
      Sexual counselling for young adults with MMC is an important part of the
      rehabilitation process.

PMID- 16882637
TI  - Location and size of infarct on functional outcome of noncardioembolic ischemic
      stroke.
AB  - PURPOSE: Studies regarding the effects of location and size of infarct on the
      functional outcome after stroke have yielded inconsistent results. This study
      aimed to investigate the relationships of neuroimage findings and longitudinal
      Barthel index (BI) scores in patients with first-ever ischemic stroke. METHOD:
      The neuroimage findings of enrolled subjects were grouped by anatomical location.
      The size of infarct was determined by the largest diameter of the lesion.
      Patients were followed up prospectively at onset, 2 weeks, 1, 2, 4, and 6 months
      after stroke. Linear mixed model was employed for the repeated measurement
      analysis of BI at these six time points in each patient. RESULTS: A total of 111
      patients were enrolled. The BI increased rapidly during the first two months, and
      reached plateau after four months. The location and size of the lesion had
      significant effects on serial measurements of BI. After adjustment for age, sex,
      treatment mode, and baseline BI score, the posterior cerebral artery infarct
      group showed the largest improvement in BI. There was a trend that the smaller
      the lesion size, the more favourable the functional outcome. CONCLUSIONS: Both
      location and size of lesion in noncardioembolic stroke were significant
      prognostic factors for functional outcome.

PMID- 16882638
TI  - Experiences of a primary health care rehabilitation programme. A focus group
      study of persons with chronic pain.
AB  - PURPOSE: The objective of the study was to describe participants' experiences of
      a rehabilitation programme for persons with chronic pain. METHOD: A qualitative
      design with focus group methodology was used. The sample consisted of 24
      individuals with chronic pain who were divided into six focus groups. The
      rehabilitation programme, which was led by an occupational therapist and a
      physiotherapist, took place at a healthcare centre and comprised 12 group
      sessions. RESULTS: The qualitative themes described the programme as a meaningful
      place to which to belong and as an encouraging environment. They also included a
      criticism of the format and content of the programme. The participants had,
      however, not reflected over their possibility of influencing parts of the
      programme, as they took for granted that it was predetermined. The themes
      furthermore described the participants' expectations of being regarded as sick,
      but also their valuing of their own contribution in taking responsibility for
      carrying out the programme and for having integrated the content and becoming
      aware of their limitations. CONCLUSIONS: The participants' experiences of the
      design, content and format of the programme were positioned between two extremes:
      A passive and an active role; their own responsibility and that of the leaders;
      weakness and ego-strength; and commitment and lack of commitment.

PMID- 16882639
TI  - A comparative study of organized class-based exercise programs versus individual
      home-based exercise programs for elderly patients following hip surgery.
AB  - PURPOSE: To evaluate and compare the effectiveness of supervised and non
      supervised exercise programs for improving health and rehabilitation outcomes for
      elderly persons following hip surgery. METHOD: Prospective, descriptive and
      quantitative study involving two groups: The class-based program (group A, n =
      34: 21 females, 13 males, mean age 79.2 years +/- 5.23) was directed and
      administered in the outpatient clinic, and a home-based program (group B, n = 29,
      17 females, 12 males, mean age 80.3 years +/- 5.74) which administered in the
      patient's home. Sixty three elderly patients began at a period of 2 weeks post
      hip surgery for open reduction with internal fixation. The training period took
      place for 14 consecutive weeks. The main outcome measures include results from
      physical performance test, functional reach test and short form-36 health survey
      questionnaire. RESULTS: Fifty five patients completed the exercise program. No
      significant difference according to gender or Body Mass Index was found between
      the groups. At the conclusion of 14 weeks of exercise training both groups
      demonstrated improvement in physical function. However, only 4 of 6 total tasks
      of a physical performance test were improved in the home-based group compared to
      improvement in all 6 tasks for the class-based group. The SF-36 scores and the
      functional reach test indicated that the class-based subjects also presented
      significant gains in contrast to no significant changes in the home exercise
      group. CONCLUSIONS: Both groups demonstrated improvement in a number of issues.
      However, there appears to be more positive health outcomes presented by the
      participants in the supervised/class-based group when compared to the non
      supervised/home-based group. And therefore, patients may select to participate to
      either a home-based or class-based regime. The clinical relevance is the
      significant of the necessity for close supervision by a professional therapist.
      In addition, the results could have some political and economical implications on
      the healthcare system.

PMID- 16882640
TI  - Dimensionality and scalability of the Motor Assessment Scale (MAS).
AB  - PURPOSE: The Motor Assessment Scale (MAS) has shown to be a reliable and valid
      instrument for measuring motor functioning for stroke patients. The purpose of
      this paper was to study dimensionality and scalability of the instrument. METHOD:
      A total number of 137 patients were evaluated at admission and on discharge. To
      study dimensionality and scalability, Partial Credit Models (PCM) were applied
      for the eight items in the instrument and also for the upper limb and lower limb
      activities separately. Studies were performed to compare subgroups such as
      young/old, men/women and diagnosis to examine if the items had the same meaning
      for the subgroups. RESULTS: The items showed the same ordering for admission and
      discharge. Infit and outfit values varied between 0.5 and 1.9 at admission and
      0.5 and 1.7 on discharge. CONCLUSIONS: We conclude that the scalability of the
      different items is not optimal. For some items, the top and/or bottom levels are
      overrepresented and for other items the middle levels tend to cluster. There
      seems to be a single construct except for one of the items. The instrument also
      showed the same meaning for the different subgroups.

PMID- 16882641
TI  - The level and time course of disability: trajectories of disability in adults and
      young elderly.
AB  - OBJECTIVES: The objectives of this study were: (i) to identify trajectories in
      the level and time course of disability, (ii) to determine the relative frequency
      of each trajectory, and (iii) to assess the relationship of these trajectories
      with age, sex and the presence of four chronic diseases (asthma/chronic
      obstructive pulmonary disease (COPD), heart disease, severe low back complaints
      and diabetes mellitus). METHODS: We used six measurements of disability and
      information on mortality from a longitudinal study in Dutch persons aged 15-74.
      We used cluster analyses to group persons with similar levels and time courses of
      disability into disability trajectories. Deaths were classified into a separate
      trajectory. Multinomial regression was used to assess the relationship of the
      trajectories with age, sex and the four chronic diseases. Information on
      disability in the last year(s) prior to death was used to examine disability
      prior to death. RESULTS: Nine trajectories of disability were identified, while
      all deaths were classified into a separate trajectory; 74% was entirely non
      disabled. The size of the other trajectories varied from 10% (permanently mildly
      disabled) to 0.5% (severely disabled with large increase in disability).
      Significant associations were found with age and, correcting for age and sex,
      with asthma/COPD, heart disease and low back complaints, but not with diabetes.
      The ORs were generally highest for trajectories characterized by severe
      disability, although disease-specific associations were also found. Among the
      deaths, 41% of the trajectories were associated with disability prior to death.
      Disability prior to death was more prevalent among persons with heart disease,
      back complaints, and asthma/COPD. CONCLUSIONS: These findings suggest that
      disability is a dynamic process, and that important differences exist within the
      'disabled' population. This is important for assessing the need for care and
      shows the limitations of modeling disability change based on two measurements
      only.

PMID- 16882642
TI  - Developing empirical models to enhance stroke rehabilitation.
AB  - PURPOSE: Models identifying functional indicators most strongly associated with
      favourable and unfavourable outcomes may bolster evidence to improve stroke
      rehabilitation assessment and intervention. This study examined the feasibility
      of decision analysis methods for developing data-driven models that examined
      associations between specific functional indicators and global disability.
      METHOD: Data were derived from functional assessment of 67 participants 3 months
      following stroke. Decision analysis methods were used to examine specific
      activity and body function indicators associated with global disability, and the
      degree of limitation or impairment that contributed to favourable and
      unfavourable outcomes, in 2 models. The feasibility of decision analysis methods
      was evaluated. RESULTS: Of the 26 activity indicators, dressing was most strongly
      associated with global disability, followed by bill mailing, shopping and
      sweeping. Of 15 body function indicators, facial weakness and mental functions
      were most strongly associated with global disability. The misclassification risk
      estimates were fair for the two models. CONCLUSIONS: Findings suggest that
      decision analysis methods show promise for developing models examining
      associations between specific functional indicators and disability. Further study
      with these methods may identify specific priorities for functional assessment and
      intervention in stroke rehabilitation.

PMID- 16882643
TI  - Temporal and spatial pattern of embolism induced by pressure collar techniques in
      twigs of Picea abies.
AB  - The pressure collar technique enables the induction of embolism in plant xylem.
      This artificial cavitation is based on air seeding processes which occur when
      specific pressure gradients between the air and water phase of the xylem are
      exceeded. Standard pressure collars and a new point injection technique, which
      builds up a local potential gradient, were used to study the time and spatial
      pattern of this process. On twigs of Norway spruce (Picea abies), the cross
      sectional and axial pattern, and the time-course of embolism formation were
      analysed via conductivity and ultrasonic measurements as well as staining
      experiments. Furthermore, the release of air from the twig surface was studied by
      immersing twig sections in water. In cross-sections, embolized areas induced by
      the point injection technique were smaller compared with the standard collar and
      restricted to a circle sector. Embolism propagated from the pressure collar
      towards the nearest distal and proximal nodes but not further. A release of air
      was also observed predominantly at the internode attached to the pressure collar.
      Embolism rates increased within minutes and reached approximately 80% loss of
      conductivity after 10 min treatment with the standard collar. The size of air
      entry points and embolism rates correlated significantly. Embolism formation in
      wood therefore depends not only on vulnerability thresholds but also on the
      extent of air-water interfaces within the xylem and on the time of exposure to
      pressure gradients. These aspects and the propagation of pressure within samples
      are crucial for pressure collar experiments. In addition, wood architecture
      influences the extent and pattern of embolism caused by air seeding processes.

PMID- 16882644
TI  - The geometry of the forisome-sieve element-sieve plate complex in the phloem of
      Vicia faba L. leaflets.
AB  - Forisomes are contractile protein bodies that appear to control flux rates in the
      phloem of faboid legumes by reversibly plugging the sieve tubes. Plugging is
      triggered by Ca(2+) which induces an anisotropic deformation of forisomes,
      consisting of a longitudinal contraction and a radial expansion. By conventional
      light microscopy and confocal laser-scanning microscopy, the three-dimensional
      geometry of the forisome-sieve element-sieve plate complex in intact sieve tubes
      of leaflets of Vicia faba L. was reconstructed. Forisomes were mostly located
      close to sieve plates, and occasionally were observed drifting unrestrainedly
      along the sieve element, suggesting that they might be utilized as internal
      markers of flow direction. The diameter of forisomes in the resting state
      correlated with the diameter of their sieve elements, supporting the idea that
      radial expansion of forisomes is the geometric basis of reversible sieve tube
      plugging. Comparison of the present results regarding forisome geometry in situ
      with previously published data on forisome reactivity in vitro makes it
      questionable, however, whether forisomes are capable of completely sealing sieve
      tubes in V. faba leaves.

PMID- 16882645
TI  - Temperature response of photosynthesis and internal conductance to CO2: results
      from two independent approaches.
AB  - The internal conductance to CO(2) transfer from intercellular spaces to
      chloroplasts poses a major limitation to photosynthesis, but few studies have
      investigated its temperature response. The aim of this study was to determine the
      temperature response of photosynthesis and internal conductance between 10
      degrees C and 35 degrees C in seedlings of a deciduous forest tree species,
      Quercus canariensis. Internal conductance was estimated via simultaneous
      measurements of gas exchange and chlorophyll fluorescence ("variable J method").
      Two of the required parameters, the intercellular photocompensation point (C(i)*)
      and rate of mitochondrial respiration in the light (R(d)), were estimated by the
      Laisk method. These were used to calculate the chloroplastic photocompensation
      point (Gamma*) in a simultaneous equation with g(i). An independent estimate of
      internal conductance was obtained by a novel curve-fitting method based on the
      curvature of the initial Rubisco-limited portion of an A/C(i) curve. The
      temperature responses of the rate of Rubisco carboxylation (V(cmax)) and the RuBP
      limited rate of electron transport (J(max)) were determined from chloroplastic
      CO(2) concentrations. The rate of net photosynthesis peaked at 24 degrees C.
      C(i)* was similar to reports for other species with a C(i)* of 39 micromol mol(
      1) at 25 degrees C and an activation energy of 34 kJ mol(-1). Gamma* was very
      similar to the published temperature response for Spinacia oleracea from 20
      degrees C to 35 degrees C, but was slightly greater at 10 degrees C and 15
      degrees C. J(max) peaked at 30 degrees C, whereas V(cmax) did not reach a maximum
      between 10 degrees C and 35 degrees C. Activation energies were 49 kJ mol(-1) for
      V(cmax) and 100 kJ mol(-1) for J(max). Both methods showed that internal
      conductance doubled from 10 degrees C to 20 degrees C, and then was nearly
      temperature-independent from 20 degrees C to 35 degrees C. Hence, the temperature
      response of internal conductance could not be fitted to an Arrhenius function.
      The best fit to estimated g(i) was obtained with a three-parameter log normal
      function (R(2)=0.98), with a maximum g(i) of 0.19 mol m(-2) s(-1) at 29 degrees
      C.

PMID- 16882646
TI  - Review of sorption and diffusion of lipophilic molecules in cuticular waxes and
      the effects of accelerators on solute mobilities.
AB  - Many agrochemicals are applied to the leaf surfaces of crop plants. Systemic
      chemicals have to penetrate through the cuticle, which forms an effective
      transport barrier. The barrier properties of cuticles are mainly due to the
      cuticular waxes deposited as partially crystalline aggregates on the outer
      surfaces of leaves. Substances increasing the mobilities of agrochemicals in
      cuticular waxes are called accelerators and it is shown that they act as
      plasticizers when absorbed by cuticular waxes. They decrease the barrier
      properties of the waxes and thus increase the mobilities of the agrochemicals
      through them. In order to analyse the efficiency of different accelerators, the
      sorption and mobility of both agrochemicals and accelerators within cuticular
      waxes was measured. Such information was used to establish correlations between
      the internal concentrations of accelerators and their mobility-enhancing effects
      on agrochemicals in the cuticle. This, in turn, allowed the determination and
      comparison of the intrinsic effects of different accelerators and to rationalize
      the effect of accelerators on the cuticular permeability of agrochemicals.
      Results describing the sorption (partition coefficients) and mobility (diffusion
      coefficients) of lipophilic organic molecules in reconstituted cuticular waxes
      from different plant species, and the effect of two different classes of
      accelerators (alcohol ethoxylates and n-alkyl esters), on the mobility of organic
      molecules are presented and discussed.

PMID- 16882647
TI  - Reliable gene signatures for microarray classification: assessment of stability
      and performance.
AB  - MOTIVATION: Two important questions for the analysis of gene expression
      measurements from different sample classes are (1) how to classify samples and
      (2) how to identify meaningful gene signatures (ranked gene lists) exhibiting the
      differences between classes and sample subsets. Solutions to both questions have
      immediate biological and biomedical applications. To achieve optimal
      classification performance, a suitable combination of classifier and gene
      selection method needs to be specifically selected for a given dataset. The
      selected gene signatures can be unstable and the resulting classification
      accuracy unreliable, particularly when considering different subsets of samples.
      Both unstable gene signatures and overestimated classification accuracy can
      impair biological conclusions. METHODS: We address these two issues by repeatedly
      evaluating the classification performance of all models, i.e. pairwise
      combinations of various gene selection and classification methods, for random
      subsets of arrays (sampling). A model score is used to select the most
      appropriate model for the given dataset. Consensus gene signatures are
      constructed by extracting those genes frequently selected over many samplings.
      Sampling additionally permits measurement of the stability of the classification
      performance for each model, which serves as a measure of model reliability.
      RESULTS: We analyzed a large gene expression dataset with 78 measurements of four
      different cartilage sample classes. Classifiers trained on subsets of
      measurements frequently produce models with highly variable performance. Our
      approach provides reliable classification performance estimates via sampling. In
      addition to reliable classification performance, we determined stable consensus
      signatures (i.e. gene lists) for sample classes. Manual literature screening
      showed that these genes are highly relevant to our gene expression experiment
      with osteoarthritic cartilage. We compared our approach to others based on a
      publicly available dataset on breast cancer. AVAILABILITY: R package at
      http://www.bio.ifi.lmu.de/~davis/edaprakt

PMID- 16882648
TI  - PYCHEM: a multivariate analysis package for python.
AB  - We have implemented a multivariate statistical analysis toolbox, with an optional
      standalone graphical user interface (GUI), using the Python scripting language.
      This is a free and open source project that addresses the need for a multivariate
      analysis toolbox in Python. Although the functionality provided does not cover
      the full range of multivariate tools that are available, it has a broad
      complement of methods that are widely used in the biological sciences. In
      contrast to tools like MATLAB, PyChem 2.0.0 is easily accessible and free, allows
      for rapid extension using a range of Python modules and is part of the growing
      amount of complementary and interoperable scientific software in Python based
      upon SciPy. One of the attractions of PyChem is that it is an open source project
      and so there is an opportunity, through collaboration, to increase the scope of
      the software and to continually evolve a user-friendly platform that has
      applicability across a wide range of analytical and post-genomic disciplines.
      AVAILABILITY: http://sourceforge.net/projects/pychem

PMID- 16882649
TI  - Nemo: an evolutionary and population genetics programming framework.
AB  - Nemo is an individual-based, genetically explicit and stochastic population
      computer program for the simulation of population genetics and life-history trait
      evolution in a metapopulation context. It comes as both a C++ programming
      framework and an executable program file. Its object-oriented programming design
      gives it the flexibility and extensibility needed to implement a large variety of
      forward-time evolutionary models. It provides developers with abstract models
      allowing them to implement their own life-history traits and life-cycle events.
      Nemo offers a large panel of population models, from the Island model to lattice
      models with demographic or environmental stochasticity and a variety of already
      implemented traits (deleterious mutations, neutral markers and more), life-cycle
      events (mating, dispersal, aging, selection, etc.) and output operators for
      saving data and statistics. It runs on all major computer platforms including
      parallel computing environments. AVAILABILITY: The source code, binaries and
      documentation are available under the GNU General Public License at
      http://nemo2.sourceforge.net.

PMID- 16882650
TI  - Partial correlation coefficient between distance matrices as a new indicator of
      protein-protein interactions.
AB  - MOTIVATION: The computational prediction of protein-protein interactions is
      currently a major issue in bioinformatics. Recently, a variety of co-evolution
      based methods have been investigated toward this goal. In this study, we
      introduced a partial correlation coefficient as a new measure for the degree of
      co-evolution between proteins, and proposed its use to predict protein-protein
      interactions. RESULTS: The accuracy of the prediction by the proposed method was
      compared with those of the original mirror tree method and the projection method
      previously developed by our group. We found that the partial correlation
      coefficient effectively reduces the number of false positives, as compared with
      other methods, although the number of false negatives increased in the prediction
      by the partial correlation coefficient. AVAILABILITY: The R script for the
      prediction of protein-protein interactions reported in this manuscript is
      available at http://timpani.genome.ad.jp/~parco/

PMID- 16882651
TI  - OSIRIS: a tool for retrieving literature about sequence variants.
AB  - Sequence variants, in particular single nucleotide polymorphisms (SNPs), are key
      elements for the identification of genes associated with complex diseases and
      with particular drug responses. The search for literature about sequence
      variation is hampered by the large number of allelic variants reported for many
      genes and by the variability in both gene and sequence variants nomenclatures. We
      describe OSIRIS, a search tool that integrates different sources of information
      with the aim to retrieve literature about sequence variation of a gene. In
      addition, it provides a method to link a dbSNP entry with the articles referring
      to it. AVAILABILITY: OSIRIS is available for public use at http://ibi.imim.es/

PMID- 16882652
TI  - Sebida: a database for the functional and evolutionary analysis of genes with sex
      biased expression.
AB  - We describe Sebida, a database of genes with sex-biased expression. The database
      integrates results from multiple, independent microarray studies comparing male
      and female gene expression in Drosophila melanogaster, Drosophila simulans and
      Anopheles gambiae. Sebida uses standard nomenclature, which allows individual
      genes to be compared across different microarray platforms and to be queried by
      gene name, symbol, or annotation number. In addition to ratios of male/female
      expression for each gene, Sebida also contains information useful for
      evolutionary studies, such as local recombination rate, degree of codon bias and
      interspecific divergence at synonymous and non-synonymous sites. AVAILABILITY:
      Sebida can be accessed at http://www.sebida.de

PMID- 16882653
TI  - Evaluation and comparison of gene clustering methods in microarray analysis.
AB  - MOTIVATION: Microarray technology has been widely applied in biological and
      clinical studies for simultaneous monitoring of gene expression in thousands of
      genes. Gene clustering analysis is found useful for discovering groups of
      correlated genes potentially co-regulated or associated to the disease or
      conditions under investigation. Many clustering methods including hierarchical
      clustering, K-means, PAM, SOM, mixture model-based clustering and tight
      clustering have been widely used in the literature. Yet no comprehensive
      comparative study has been performed to evaluate the effectiveness of these
      methods. RESULTS: In this paper, six gene clustering methods are evaluated by
      simulated data from a hierarchical log-normal model with various degrees of
      perturbation as well as four real datasets. A weighted Rand index is proposed for
      measuring similarity of two clustering results with possible scattered genes
      (i.e. a set of noise genes not being clustered). Performance of the methods in
      the real data is assessed by a predictive accuracy analysis through verified gene
      annotations. Our results show that tight clustering and model-based clustering
      consistently outperform other clustering methods both in simulated and real data
      while hierarchical clustering and SOM perform among the worst. Our analysis
      provides deep insight to the complicated gene clustering problem of expression
      profile and serves as a practical guideline for routine microarray cluster
      analysis.

PMID- 16882654
TI  - Local similarity analysis reveals unique associations among marine
      bacterioplankton species and environmental factors.
AB  - MOTIVATION: Characterizing the diversity of microbial communities and
      understanding the environmental factors that influence community diversity are
      central tenets of microbial ecology. The development and application of
      cultivation independent molecular tools has allowed for rapid surveying of
      microbial community composition at unprecedented resolutions and frequencies.
      There is a growing need to discern robust patterns and relationships within these
      datasets which provide insight into microbial ecology. Pearson correlation
      coefficient (PCC) analysis is commonly used for identifying the linear
      relationship between two species, or species and environmental factors. However,
      this approach may not be able to capture more complex interactions which occur in
      situ; thus, alternative analyses were explored. RESULTS: In this paper we
      introduced local similarity analysis (LSA), which is a technique that can
      identify more complex dependence associations among species as well as
      associations between species and environmental factors without requiring
      significant data reduction. To illustrate its capability of identifying
      relationships that may not otherwise be identified by PCC, we first applied LSA
      to simulated data. We then applied LSA to a marine microbial observatory dataset
      and identified unique, significant associations that were not detected by PCC
      analysis. LSA results, combined with results from PCC analysis were used to
      construct a theoretical ecological network which allows for easy visualization of
      the most significant associations. Biological implications of the significant
      associations detected by LSA were discussed. We also identified additional
      applications where LSA would be beneficial. AVAILABILITY: The algorithms are
      implemented in Splus/R and they are available upon request from the corresponding
      author.

PMID- 16882655
TI  - P2Y1 receptor-evoked glutamate exocytosis from astrocytes: control by tumor
      necrosis factor-alpha and prostaglandins.
AB  - ATP, released by both neurons and glia, is an important mediator of brain
      intercellular communication. We find that selective activation of purinergic P2Y1
      receptors (P2Y1R) in cultured astrocytes triggers glutamate release. By total
      internal fluorescence reflection imaging of fluorescence-labeled glutamatergic
      vesicles, we document that such release occurs by regulated exocytosis. The
      stimulus-secretion coupling mechanism involves Ca2+ release from internal stores
      and is controlled by additional transductive events mediated by tumor necrosis
      factor-alpha (TNFalpha) and prostaglandins (PG). P2Y1R activation induces release
      of both TNFalpha and PGE2 and blocking either one significantly reduces glutamate
      release. Accordingly, astrocytes from TNFalpha-deficient (TNF(-/-)) or TNF type 1
      receptor-deficient (TNFR1(-/-)) mice display altered P2Y1R-dependent Ca2+
      signaling and deficient glutamate release. In mixed hippocampal cultures, the
      P2Y1R-evoked process occurs in astrocytes but not in neurons or microglia. P2Y1R
      stimulation induces Ca2+ -dependent glutamate release also from acute hippocampal
      slices. The process in situ displays characteristics resembling those in cultured
      astrocytes and is distinctly different from synaptic glutamate release evoked by
      high K+ stimulation as follows: (a) it is sensitive to cyclooxygenase inhibitors;
      (b) it is deficient in preparations from TNF(-/-) and TNFR1(-/-) mice; and (c) it
      is inhibited by the exocytosis blocker bafilomycin A1 with a different time
      course. No glutamate release is evoked by P2Y1R-dependent stimulation of
      hippocampal synaptosomes. Taken together, our data identify the coupling of
      purinergic P2Y1R to glutamate exocytosis and its peculiar TNFalpha- and PG
      dependent control, and we strongly suggest that this cascade operates selectively
      in astrocytes. The identified pathway may play physiological roles in glial-glial
      and glial-neuronal communication.

PMID- 16882656
TI  - Perlecan proteolysis induces an alpha2beta1 integrin- and Src family kinase
      dependent anti-apoptotic pathway in fibroblasts in the absence of focal adhesion
      kinase activation.
AB  - Dysregulation of apoptosis in endothelial cells (EC) and fibroblasts contributes
      to fibrosis. We have shown previously that apoptosis of EC triggers the
      proteolysis of extracellular matrix components and the release of a C-terminal
      fragment of perlecan, which in turn inhibits apoptosis of fibroblasts. Here we
      have defined the receptors and pathways implicated in this anti-apoptotic
      response in fibroblasts. Neutralizing alpha2beta1 integrin activity in
      fibroblasts exposed to either medium conditioned by apoptotic EC (SSC) or a
      recombinant perlecan C-terminal fragment (LG3) prevented resistance to apoptosis
      and is associated with decreased levels of Akt phosphorylation. Co-incubation of
      fibroblasts for 24 h with SSC or LG3 in the presence of PP2 (AG1879), a
      biochemical inhibitor of Src family kinases (SFKs) and focal adhesion kinase,
      showed a significantly decreased anti-apoptotic response. However, focal adhesion
      kinase gene silencing with RNA interference did not inhibit the anti-apoptotic
      response in fibroblasts. Src phosphorylation was increased in fibroblasts exposed
      to SSC, and transfection of fibroblasts with constitutively active Src mutants
      induced an anti-apoptotic response that was not further increased by SSC. Also,
      Src(-/-)Fyn(-/-) fibroblasts failed to mount an anti-apoptotic response in
      presence of SSC for 24 h but developed a complete anti-apoptotic response when
      exposed to SSC for 7 days. These results suggest that extracellular matrix
      fragments produced by apoptotic EC initiate a state of resistance to apoptosis in
      fibroblasts via an alpha2beta1 integrin/SFK (Src and Fyn)/phosphatidylinositol 3
      kinase (PI3K)-dependent pathway. In the long term, additional SFK members are
      recruited for sustaining the anti-apoptotic response, which could play crucial
      roles in abnormal fibrogenic healing.

PMID- 16882657
TI  - The phylogenetically conserved molluscan chitinase-like protein 1 (Cg-Clp1),
      homologue of human HC-gp39, stimulates proliferation and regulates synthesis of
      extracellular matrix components of mammalian chondrocytes.
AB  - Members of chitinase-like proteins (CLPs) have attracted much attention because
      of their ability to promote cell proliferation in insects (imaginal disc growth
      factors) and mammals (YKL-40). To gain insights into the molecular processes
      underlying the physiological control of growth and development in Lophotrochozoa,
      we report here the cloning and biochemical characterization of the first
      Lophotrochozoan CLP from the oyster Crassostrea gigas (Cg-Clp1). Gene expression
      profiles monitored by real time quantitative reverse transcription-PCR in
      different adult tissues and during development support the involvement of this
      protein in the control of growth and development in C. gigas. Recombinant Cg-Clp1
      demonstrates a strong affinity for chitin but no chitinolytic activity, as was
      described for the HC-gp39 mammalian homolog. Furthermore, transient expression of
      Cg-Clp1 in primary cultures of rabbit articular chondrocytes as well as the use
      of both purified recombinant protein and conditioned medium from Cg-Clp1
      expressing rabbit articular chondrocytes established that Cg-Clp1 stimulates cell
      proliferation and regulates extracellular matrix component synthesis, showing for
      the first time a possible involvement of a CLP on type II collagen synthesis
      regulation. These observations together with the fact that Cg-Clp1 gene
      organization strongly resembles that of its mammalian homologues argue for an
      early evolutionary origin and a high conservation of this class of proteins at
      both the structural and functional levels.

PMID- 16882659
TI  - Signal peptide peptidase cleavage of GB virus B core protein is required for
      productive infection in vivo.
AB  - Chronic infection by hepatitis C virus (HCV) is a leading cause of liver disease
      for which better therapies are urgently needed. Because a clearer understanding
      of the viral life cycle may suggest novel anti-viral approaches, we studied the
      role of host signal peptide peptidase (SPP) in viral infection. This
      intramembrane protease cleaves within a C-terminal signal sequence in the viral
      core protein, but the molecular determinants of cleavage and whether it is
      required for infection in vivo are unknown. To answer these questions, we studied
      SPP processing in GB virus B (GBV-B) infection. GBV-B is the closest phylogenetic
      relative of HCV and offers an accurate surrogate model for HCV infection. We
      demonstrate that SPP also processes GBV-B core protein and that a serine residue
      in the hydrophobic region of the signal sequence (present also in HCV) is
      critical for efficient SPP cleavage. The small size of the serine side chain
      combined with its ability to form intra- and interhelical hydrogen bonds likely
      contributes to recognition of the signal sequence as a substrate for SPP. By
      introducing mutations with differing effects on SPP processing into an infectious
      GBV-B molecular clone, we demonstrate that SPP processing of the core protein is
      required for productive infection in primates. These results broaden our
      understanding of the mechanism and requirements for SPP cleavage and reveal a
      functional role in vivo for intramembrane proteolysis in host-pathogen
      interactions. Moreover, they identify SPP as a potential therapeutic target for
      reducing the impact of HCV infection.

PMID- 16882658
TI  - A subfamily of Dr adhesins of Escherichia coli bind independently to decay
      accelerating factor and the N-domain of carcinoembryonic antigen.
AB  - Escherichia coli expressing the Dr family of adhesins adheres to epithelial cells
      by binding to decay-accelerating factor (DAF) and carcinoembryonic antigen (CEA)
      related cell surface proteins. The attachment of bacteria expressing Dr adhesins
      to DAF induces clustering of DAF around bacterial cells and also recruitment of
      CEA-related cell adhesion molecules. CEA, CEACAM1, and CEACAM6 have been shown to
      serve as receptors for some Dr adhesins (AfaE-I, AfaE-III, DraE, and DaaE). We
      demonstrate that AfaE-I, AfaE-V, DraE, and DaaE adhesins bind to the N-domain of
      CEA. To identify the residues involved in the N-CEA/DraE interaction, we
      performed SPR binding analyses of naturally occurring variants and a number of
      randomly generated mutants in DraE and N-CEA. Additionally, we used chemical
      shift mapping by NMR to determine the surface of DraE involved in N-CEA binding.
      These results show a distinct CEA binding site located primarily in the A, B, E,
      and D strands of the Dr adhesin. Interestingly, this site is located opposite to
      the beta-sheet encompassing the previously determined binding site for DAF, which
      implies that the adhesin can bind simultaneously to both receptors on the
      epithelial cell surface. The recognition of CEACAMs from a highly diverse DrCEA
      subfamily of Dr adhesins indicates that interaction with these receptors plays an
      important role in niche adaptation of E. coli strains expressing Dr adhesins.

PMID- 16882660
TI  - Modulation of acid-sensing ion channel currents, acid-induced increase of
      intracellular Ca2+, and acidosis-mediated neuronal injury by intracellular pH.
AB  - Acid-sensing ion channels (ASICs), activated by lowering extracellular pH
      (pH(o)), play an important role in normal synaptic transmission in brain and in
      the pathology of brain ischemia. Like pH(o), intracellular pH (pH(i)) changes
      dramatically in both physiological and pathological conditions. Although it is
      known that a drop in pH(o) activates the ASICs, it is not clear whether
      alterations of pH(i) have an effect on these channels. Here we demonstrate that
      the overall activities of ASICs, including channel activation, inactivation, and
      recovery from desensitization, are tightly regulated by pH(i). In cultured mouse
      cortical neurons, bath perfusion of the intracellular alkalizing agent quinine
      increased the amplitude of the ASIC current by approximately 50%. In contrast,
      intracellular acidification by withdrawal of NH(4)Cl or perfusion of propionate
      inhibited the current. Increasing pH buffering capacity in the pipette solution
      with 40 mm HEPES attenuated the effects of quinine and NH(4)Cl. The effects of
      intracellular alkalizing/acidifying agents were mimicked by using intracellular
      solutions with pH directly buffered at high/low values. Increasing pH(i) induced
      a shift in H(+) dose-response curve toward less acidic pH but a shift in the
      steady state inactivation curve toward more acidic pH. In addition, alkalizing
      pH(i) induced an increase in the recovery rate of ASICs from desensitization.
      Consistent with its effect on the ASIC current, changing pH(i) has a significant
      influence on the acid-induced increase of intracellular Ca(2+), membrane
      depolarization, and acidosis-mediated neuronal injury. Our findings suggest that
      changes in pH(i) may play an important role in determining the overall function
      of ASICs in both physiological and pathological conditions.

PMID- 16882661
TI  - Crystallographic analysis of calcium-dependent heparin binding to annexin A2.
AB  - Annexin A2 and heparin bind to one another with high affinity and in a calcium
      dependent manner, an interaction that may play a role in mediating fibrinolysis.
      In this study, three heparin-derived oligosaccharides of different lengths were
      co-crystallized with annexin A2 to elucidate the structural basis of the
      interaction. Crystal structures were obtained at high resolution for uncomplexed
      annexin A2 and three complexes of heparin oligosaccharides bound to annexin A2.
      The common heparin-binding site is situated at the convex face of domain IV of
      annexin A2. At this site, annexin A2 binds up to five sugar residues from the
      nonreducing end of the oligosaccharide. Unlike most heparin-binding consensus
      patterns, heparin binding at this site does not rely on arrays of basic residues;
      instead, main-chain and side-chain nitrogen atoms and two calcium ions play
      important roles in the binding. Especially significant is a novel calcium-binding
      site that forms upon heparin binding. Two sugar residues of the heparin
      derivatives provide oxygen ligands for this calcium ion. Comparison of all four
      structures shows that heparin binding does not elicit a significant
      conformational change in annexin A2. Finally, surface plasmon resonance
      measurements were made for binding interactions between annexin A2 and heparin
      polysaccharide in solution at pH 7.4 or 5.0. The combined data provide a clear
      basis for the calcium dependence of heparin binding to annexin A2.

PMID- 16882662
TI  - Fibronectin increases matrix metalloproteinase 9 expression through activation of
      c-Fos via extracellular-regulated kinase and phosphatidylinositol 3-kinase
      pathways in human lung carcinoma cells.
AB  - Enhanced expression of matrix metalloproteinase-9 (MMP-9) is associated with
      human lung tumor invasion and/or metastasis. We have demonstrated that
      fibronectin (FN), a matrix glycoprotein, stimulates human non-small cell lung
      carcinoma (NSCLC) cell proliferation. The current study examines the effect of FN
      on MMP-9 expression in NSCLC cells. We show that FN increases MMP-9 protein, mRNA
      expression, and gelatinolytic activity in NSCLC cells. The integrin alpha5beta1
      mediated the effects of FN because alpha5 small interfering RNA blocked FN
      stimulated MMP-9 protein expression, and also abrogated FN-induced
      phosphorylation of ERK and phosphatidylinositol 3-kinase (PI3K) signals. The
      inhibitor of ERK, PD98095, and of PI3K, wortmannin, but not that of protein
      kinase A, H89, of Rho kinase, Y-27632, of mTOR, rapamycin, or of JNK, SP600125,
      prevented FN-induced MMP-9 gelatinolytic activity and gene expression. FN
      enhanced MMP-9 gene promoter activity; however, there was no response to FN in
      DNA constructs with an AP-1 site mutation. FN increased AP-1 DNA binding
      activity, and this was abrogated by cyclic AMP response element decoy
      oligonucleotides, which also diminished FN-induced MMP-9 promoter activity. FN
      increased the expression of the AP-1 subunit c-Fos protein, but not in the
      presence of PD98095 and wortmannin. The AP-1 inhibitor, nordihydroguaiaretic
      acid, and a c-Fos small interfering RNA eliminated the effect of FN on MMP-9
      expression. This study indicates that FN, by binding to the integrin alpha5beta1
      receptor, stimulates the expression of MMP-9 through increased AP-1/DNA binding
      and c-Fos protein expression via ERK and PI3K signaling pathways. The data
      unveils a novel mechanism by which FN could promote NSCLC cell invasion and
      metastasis.

PMID- 16882663
TI  - Inhibition of HIV-1 replication by amphotericin B methyl ester: selection for
      resistant variants.
AB  - Membrane cholesterol plays an important role in human immunodeficiency virus type
      1 (HIV-1) particle production and infectivity. Here, we have investigated the
      target and mechanism of action of a cholesterol-binding compound, the polyene
      antifungal antibiotic amphotericin B methyl ester (AME). We found that AME
      potently inhibited the replication of a highly divergent panel of HIV-1 isolates
      in various T-cell lines and primary cells irrespective of clade or target cell
      tropism. The defects in HIV-1 replication caused by AME were due to profoundly
      impaired viral infectivity as well as a defect in viral particle production. To
      elucidate further the mechanism of action of AME, we selected for and
      characterized AME-resistant HIV-1 variants. Mutations responsible for AME
      resistance mapped to a highly conserved and functionally important endocytosis
      motif in the cytoplasmic tail of the transmembrane glycoprotein gp41.
      Interestingly, truncation of the gp41 cytoplasmic tail in the context of either
      HIV-1 or rhesus macaque simian immunodeficiency virus also conferred resistance
      to AME. The infectivity of HIV-1 virions bearing murine leukemia virus or
      vesicular stomatitis virus glycoproteins was unaffected by AME. Our data define
      the target and mechanism of action of AME and provide support for the concept
      that cholesterol-binding compounds should be pursued as antiretroviral drugs to
      disrupt HIV-1 replication.

PMID- 16882664
TI  - Jab1 mediates cytoplasmic localization and degradation of West Nile virus capsid
      protein.
AB  - The clinical manifestations of West Nile virus (WNV), a member of the Flavivirus
      family, include febrile illness, sporadic encephalitis, and paralysis. The capsid
      (Cp) of WNV is thought to participate in these processes by inducing apoptosis
      through mitochondrial dysfunction and activation of caspase-9 and caspase-3. To
      further identify the molecular mechanism of the WNV capsid protein (WNVCp), yeast
      two-hybrid assays were employed using WNV-Cp as bait. Jab1, the fifth subunit of
      the COP9 signalosome, was subsequently identified as a molecule that interacts
      with WNVCp. Immunoprecipitation and glutathione S-transferase pulldown assays
      confirmed that direct interaction could occur between WNVCp and Jab1.
      Immunofluorescence microscopy demonstrated that the overexpressed WNVCp, which
      localized to the nucleolus, was translocated to the cytoplasm upon its co
      expression with Jab1. When treated with leptomycin B, Jab1-facilitated nuclear
      exclusion of WNVCp was prevented, which indicated that the CRM1 complex is
      required for Jab1-facilitated nuclear export of WNVCp. Moreover, Jab1 promoted
      the degradation of WNVCp in a proteasome-dependent way. Consistent with this,
      WNVCp-mediated cell cycle arrest at the G(2) phase in H1299 was prevented by
      exogenous Jab1. Finally, an analysis of WNVCp deletion mutants indicated that the
      first 15 amino acids were required for interaction with Jab1. Furthermore, the
      double-point mutant of the WNVCp, P5A/P8A, was incapable of binding to Jab1.
      These results indicate that Jab1 has a potential protective effect against
      pathogenic WNVCp and might provide a novel target site for the treatment of
      disease caused by WNV.

PMID- 16882665
TI  - Regulation of gephyrin assembly and glycine receptor synaptic stability.
AB  - Gephyrin is required for the formation of clusters of the glycine receptor (GlyR)
      in the neuronal postsynaptic membrane. It can make trimers and dimers through its
      N- and C-terminal G and E domains, respectively. Gephyrin oligomerization could
      thus create a submembrane lattice providing GlyR-binding sites. We investigated
      the relationships between the stability of cell surface GlyR and the ability of
      gephyrin splice variants to form oligomers. Using truncated and full-length
      gephyrins we found that the 13-amino acid sequence (cassette 5) prevents G domain
      trimerization. Moreover, E domain dimerization is inhibited by the gephyrin
      central L domain. All of the gephyrin variants bind GlyR beta subunit cytoplasmic
      loop with high affinity regardless of their cassette composition. Coexpression
      experiments in COS-7 cells demonstrated that GlyR bound to gephyrin harboring
      cassette 5 cannot be stabilized at the cell surface. This gephyrin variant was
      found to deplete synapses from both GlyR and gephyrin in transfected neurons.
      These data suggest that the relative expression level of cellular variants
      influence the overall oligomerization pattern of gephyrin and thus the turnover
      of synaptic GlyR.

PMID- 16882666
TI  - Cytoplasmic CstF-77 protein belongs to a masking complex with cytoplasmic
      polyadenylation element-binding protein in Xenopus oocytes.
AB  - Regulated mRNA translation is a hallmark of oocytes and early embryos, of which
      cytoplasmic polyadenylation is a major mechanism. This process involves multiple
      protein components, including the CPSF (cleavage and polyadenylation specificity
      factor), which is also required for nuclear polyadenylation. The CstF (cleavage
      stimulatory factor), with CPSF, is required for the pre-mRNA cleavage before
      nuclear polyadenylation. However, some evidence suggests that the CstF-77 subunit
      might have a function independent of nuclear polyadenylation, which could be
      related to the cell cycle. As such, we addressed the question whether CstF-77
      might have a role in cytoplasmic polyadenylation. We investigated the function of
      the CstF-77 protein in Xenopus oocytes, and show that CstF-77 has indeed a role
      in the cytoplasm. The Xenopus CstF-77 protein (X77K) localizes mainly to the
      nucleus, but also in punctuate cytoplasmic foci. We show that X77K resides in a
      cytoplasmic complex with eIF4E, CPEB (cytoplasmic polyadenylation element-binding
      protein), CPSF-100 and XGLD2, but is not required for cytoplasmic polyadenylation
      per se. Impairment of X77K function in ovo leads to an acceleration of the G(2)/M
      transition, with a premature synthesis of Mos and AuroraA proteins. However, the
      kinetic of Mos mRNA polyadenylation is not modified. Furthermore, X77K represses
      mRNA translation in vitro. These results suggest that X77K could be involved in
      masking of mRNA prior to polyadenylation.

PMID- 16882667
TI  - Knock-downs of iron-sulfur cluster assembly proteins IscS and IscU down-regulate
      the active mitochondrion of procyclic Trypanosoma brucei.
AB  - Transformation of the metabolically down-regulated mitochondrion of the mammalian
      bloodstream stage of Trypanosoma brucei to the ATP-producing mitochondrion of the
      insect procyclic stage is accompanied by the de novo synthesis of citric acid
      cycle enzymes and components of the respiratory chain. Because these metabolic
      pathways contain multiple iron-sulfur (FeS) proteins, their synthesis, including
      the formation of FeS clusters, is required. However, nothing is known about FeS
      cluster biogenesis in trypanosomes, organisms that are evolutionarily distant
      from yeast and humans. Here we demonstrate that two mitochondrial proteins, the
      cysteine desulfurase TbiscS and the metallochaperone TbiscU, are functionally
      conserved in trypanosomes and essential for this parasite. Knock-downs of TbiscS
      and TbiscU in the procyclic stage by means of RNA interference resulted in
      reduced activity of the marker FeS enzyme aconitase in both the mitochondrion and
      cytosol because of the lack of FeS clusters. Moreover, down-regulation of TbiscS
      and TbiscU affected the metabolism of procyclic T. brucei so that their
      mitochondria resembled the organelle of the bloodstream stage; mitochondrial ATP
      production was impaired, the activity of the respiratory chain protein complex
      ubiquinol-cytochrome-c reductase was reduced, and the production of pyruvate as
      an end product of glucose metabolism was enhanced. These results indicate that
      mitochondrial FeS cluster assembly is indispensable for completion of the T.
      brucei life cycle.

PMID- 16882668
TI  - Caspase-3-dependent activation of calcium-independent phospholipase A2 enhances
      cell migration in non-apoptotic ovarian cancer cells.
AB  - Calcium-independent phospholipase A(2) (iPLA(2)) plays a pivotal role in
      phospholipid remodeling and many other biological processes, including
      inflammation and cancer development. iPLA(2) can be activated by caspase-3 via a
      proteolytic process in apoptotic cells. In this study we identify novel signaling
      and functional loops of iPLA(2) activation leading to migration of non-apoptotic
      human ovarian cancer cells. The extracellular matrix protein, laminin-10/11, but
      not collagen I, induces integrin- and caspase-3-dependent cleavage and activation
      of overexpressed and endogenous iPLA(2). The truncated iPLA(2) (amino acids 514
      806) generates lysophosphatidic acid and arachidonic acid. Arachidonic acid is
      important for enhancing cell migration toward laminin-10/11. Lysophosphatidic
      acid activates Akt that in turn acts in a feedback loop to block the cleavage of
      poly-(ADP-ribose) polymerase and DNA fragmentation factor as well as prevent
      apoptosis. By using pharmacological inhibitors, blocking antibodies, and genetic
      approaches (such as point mutations, dominant negative forms of genes, and siRNAs
      against specific targets), we show that beta(1), but not beta(4), integrin is
      involved in iPLA(2) activation and cell migration to laminin-10/11. The role of
      caspase-3 in iPLA(2) activation and cell migration are supported by several lines
      of evidence. 1) Point mutation of Asp(513) (a cleavage site of caspase-3 in
      iPLA(2)) to Ala blocks laminin-10/11-induced cleavage and activation of
      overexpressed iPLA(2), whereas mutation of Asp(733) to Ala has no such effect, 2)
      treatment of inhibitors or a small interfering RNA against caspase-3 results in
      decreased cell migration toward laminin-10/11, and 3) selective caspase-3
      inhibitor blocks cleavage of endogenous iPLA(2) induced by laminin-10/11.
      Importantly, small interfering RNA-mediated down-regulation of endogenous iPLA(2)
      expression in ovarian carcinoma HEY cells results in decreased migration toward
      laminin, suggesting that our findings are pathophysiologically important.

PMID- 16882669
TI  - Enhancing macroautophagy protects against ischemia/reperfusion injury in cardiac
      myocytes.
AB  - Cardiac myocytes undergo programmed cell death as a result of
      ischemia/reperfusion (I/R). One feature of I/R injury is the increased presence
      of autophagosomes. However, to date it is not known whether macroautophagy
      functions as a protective pathway, contributes to programmed cell death, or is an
      irrelevant event during cardiac I/R injury. We employed simulated I/R of cardiac
      HL-1 cells as an in vitro model of I/R injury to the heart. To assess
      macroautophagy, we quantified autophagosome generation and degradation
      (autophagic flux), as determined by steady-state levels of autophagosomes in
      relation to lysosomal inhibitor-mediated accumulation of autophagosomes. We found
      that I/R impaired both formation and downstream lysosomal degradation of
      autophagosomes. Overexpression of Beclin1 enhanced autophagic flux following I/R
      and significantly reduced activation of pro-apoptotic Bax, whereas RNA
      interference knockdown of Beclin1 increased Bax activation. Bcl-2 and Bcl-x(L)
      were protective against I/R injury, and expression of a Beclin1 Bcl-2/-x(L)
      binding domain mutant resulted in decreased autophagic flux and did not protect
      against I/R injury. Overexpression of Atg5, a component of the autophagosomal
      machinery downstream of Beclin1, did not affect cellular injury, whereas
      expression of a dominant negative mutant of Atg5 increased cellular injury. These
      results demonstrate that autophagic flux is impaired at the level of both
      induction and degradation and that enhancing autophagy constitutes a powerful and
      previously uncharacterized protective mechanism against I/R injury to the heart
      cell.

PMID- 16882670
TI  - Effect of the substitution of muscle actin-specific subdomain 1 and 2 residues in
      yeast actin on actin function.
AB  - Muscle and yeast actins display distinct behavioral characteristics. To better
      understand the allosteric interactions that regulate actin function, we created a
      muscle/yeast hybrid actin containing a muscle-specific outer domain (subdomains 1
      and 2) and a yeast inner domain (subdomains 3 and 4). Actin with muscle subdomain
      1 and the two yeast N-terminal negative charges supported viability. The four
      negative charge muscle N terminus in a muscle subdomain 1 background caused
      death, but in the same background actin with three N-terminal acidic residues
      (3Ac/Sub1) led to sick but viable cells. Addition of three muscle subdomain 2
      residues (3Ac/Sub12) produced no further deleterious effects. These hybrid actins
      caused depolarized cytoskeletons, abnormal vacuoles, and mitochondrial and
      endocytosis defects. 3Ac/Sub1 G-actin exchanged bound epsilonATP more slowly than
      wild type actin, and the exchange rate for 3Ac/Sub12 was even slower, similar to
      that for muscle actin. The mutant actins polymerized faster and produced less
      stable and shorter filaments than yeast actin, the opposite of that expected for
      muscle actin. Unlike wild type actin, in the absence of unbound ATP,
      polymerization led to ADP-F-actin, which rapidly depolymerized. Like yeast actin,
      the hybrid actins activated muscle myosin S1 ATPase activity only about one
      eighth as well as muscle actin, despite having essentially a muscle actin
      specific myosin-binding site. Finally, the hybrid actins behaved abnormally in a
      yeast Arp2/3-dependent polymerization assay. Our results demonstrate a unique
      sensitivity of yeast to actin N-terminal negative charge density. They also
      provide insight into the role of each domain in the control of the various
      functions of actin.

PMID- 16882671
TI  - Alterations of tension-dependent ATP utilization in a transgenic rat model of
      hypertrophic cardiomyopathy.
AB  - Although it is established that familial hypertrophic cardiomyopathy (FHC) is
      caused by mutations in several sarcomeric proteins, including cardiac troponin T
      (TnT), its pathogenesis is still not completely understood. Previously, we
      established a transgenic rat model of FHC expressing a human TnT molecule with a
      truncation mutation (DEL-TnT). This study investigated whether contractile
      dysfunction and electrical vulnerability observed in DEL-TnT rats might be due to
      alterations of intracellular Ca(2+) homeostasis, myofibrillar Ca(2+) sensitivity,
      and/or myofibrillar ATP utilization. Simultaneous measurements of the force of
      contraction and intracellular Ca(2+) transients were performed in right
      ventricular trabeculae of DEL-TnT hearts at 0.25 and 1.0 Hz. Rats expressing wild
      type human TnT as well as nontransgenic rats served as controls. In addition,
      calcium-dependent ATPase activity and tension development were investigated in
      skinned cardiac muscle fibers. Force of contraction was significantly decreased
      in DEL-TnT compared with nontransgenic rats and TnT. Time parameters of Ca(2+)
      transients were unchanged at 0.25 Hz but prolonged at 1.0 Hz in DEL-TnT. The
      amplitude of the fura-2 transient was similar in all groups investigated, whereas
      diastolic and systolic fura-2 ratios were found elevated in rats expressing
      nontruncated human troponin T. In DEL-TnT rats, myofibrillar Ca(2+)-dependent
      tension development as well as Ca(2+) sensitivity of tension were significantly
      decreased, whereas tension-dependent ATP consumption ("tension cost") was
      markedly increased. Thus, a C-terminal truncation of the cardiac TnT molecule
      impairs the force-generating capacity of the cycling cross-bridges resulting in
      increased tension-dependent ATP utilization. Taken together, our data support the
      hypothesis of energy compromise as a contributing factor in the pathogenesis of
      FHC.

PMID- 16882672
TI  - ATP regulation in adult rat cardiomyocytes: time-resolved decoding of rapid
      mitochondrial calcium spiking imaged with targeted photoproteins.
AB  - The mechanisms that enable the heart to rapidly increase ATP supply in line with
      increased demand have not been fully elucidated. Here we used an adenoviral
      system to express the photoproteins luciferase and aequorin, targeted to the
      mitochondria or cytosol of adult cardiomyocytes, to investigate the
      interrelationship between ATP and Ca(2+) in these compartments. In neither
      compartment were changes in free [ATP] observed upon increased workload (addition
      of isoproterenol) in myocytes that were already beating. However, when myocytes
      were stimulated to beat rapidly from rest, in the presence of isoproterenol, a
      significant but transient drop in mitochondrial [ATP] ([ATP](m)) occurred (on
      average to 10% of the initial signal). Corresponding changes in cytosolic [ATP]
      ([ATP](c)) were much smaller (<5%), indicating that [ATP](c) was effectively
      buffered in this compartment. Although mitochondrial [Ca(2+)] ([Ca(2+)](m)) is an
      important regulator of respiratory chain activity and ATP production in other
      cells, the kinetics of mitochondrial Ca(2+) transport are controversial. Parallel
      experiments in cells expressing mitochondrial aequorin showed that the drop in
      [ATP](m) occurred over the same time scale as average [Ca(2+)](m) was increasing.
      Conversely, in the absence or presence of isoproterenol, clear beat-to-beat peaks
      in [Ca(2+)](m) were observed at 0.9 or 1.3 mum, respectively, concentrations
      similar to those observed in the cytosol. These results suggest that
      mitochondrial Ca(2+) transients occur during the contractile cycle and are
      translated into a time-averaged increase in mitochondrial ATP production that
      keeps pace with increased cytosolic demand.

PMID- 16882673
TI  - Maternal and biochemical predictors of spontaneous preterm birth among
      nulliparous women: a systematic analysis in relation to the degree of
      prematurity.
AB  - BACKGROUND: Nulliparous women are at increased risk of spontaneous preterm birth.
      Other maternal and biochemical risk factors have also been described. However, it
      is unclear whether these associations are strong enough to offer clinically
      useful prediction. It is also unclear whether the predictive power of these
      factors varies in relation to the degree of prematurity. METHODS: The risk of
      spontaneous preterm birth associated with maternal characteristics and second
      trimester serum screening data was analysed in a dataset of 84 391 first births
      in Scotland between 1992 and 2001 using Cox and logistic regression. Variation in
      the relative risk of preterm birth over the period 24-36 weeks was assessed using
      a test of the proportional hazards assumption. RESULTS: The risk of spontaneous
      preterm birth was positively associated with maternal serum levels of alpha
      fetoprotein, socioeconomic deprivation, number of previous therapeutic abortions,
      smoking, and being unmarried and was negatively associated with height and body
      mass index. The risk of preterm birth at 24-28 weeks, but not later gestations,
      was increased in association with maternal levels of human chorionic
      gonadotrophin >95th percentile, maternal age <20, and two or more previous
      miscarriages. The area under the receiver operating characterise curve (95% CI)
      for models based on these factors was 0.67 (0.63-0.71) for 24-28 weeks, 0.65
      (0.62-0.68) for 29-32 weeks, and 0.62 (0.61-0.63) for 33-36 weeks. CONCLUSIONS:
      Time to event analytic methods can identify factors that are differentially
      associated with spontaneous preterm birth according to the degree of prematurity.
      However, models based on maternal and biochemical data perform poorly as a
      screening test for any degree of spontaneous preterm birth.

PMID- 16882674
TI  - Bifunctional antibody-Renilla luciferase fusion protein for in vivo optical
      detection of tumors.
AB  - An anti-carcinoembryonic antigen (CEA) antibody fragment, the anti-CEA diabody,
      was fused to the bioluminescence enzyme Renilla luciferase (RLuc) to generate a
      novel optical imaging probe. Native RLuc or one of two stabilized variants
      (RLucC124A, RLuc8) was used as the bioluminescent moiety. A bioluminescence ELISA
      showed that diabody-luciferase could simultaneously bind to CEA and emit light.
      In vivo optical imaging of tumor-bearing mice demonstrated specific targeting of
      diabody-RLuc8 to CEA-positive xenografts, with a tumor:background ratio of 6.0 +/
      0.8 at 6 h after intravenous injection, compared with antigen-negative tumors at
      1.0 +/- 0.1 (P = 0.05). Targeting and distribution was also evaluated by microPET
      imaging using (124)I-diabody-RLuc8 and confirmed that the optical signal was due
      to antibody-mediated localization of luciferase. Renilla luciferase, fused to
      biospecific sequences such as engineered antibodies, can be administered
      systemically to provide a novel, sensitive method for optical imaging based on
      expression of cell surface receptors in living organisms.

PMID- 16882675
TI  - Multiple processing of Ig-Hepta/GPR116, a G protein-coupled receptor with
      immunoglobulin (Ig)-like repeats, and generation of EGF2-like fragment.
AB  - Ig-Hepta/GPR116 is a member of the LNB-TM7 subfamily of G protein-coupled
      receptors (GPCRs), also termed the adhesion GPCRs, whose members have EGF,
      cadherin, lectin, thrombospondin, or Ig repeats in their long N-terminus. In this
      study, we established that Ig-Hepta is processed at multiple sites yielding the
      following four fragments: (i) presequence (amino acid residues 1-24), (ii)
      proEGF2 (25-223, alpha-fragment), (iii) Ig repeats (224-993, beta-chain), and
      (iv) TM7 (994-1349, gamma-chain). The proEGF2 region is converted to EGF2 (52
      223) by the processing enzyme furin and remains attached to the beta- and gamma
      chains. Expression of some mRNA species was affected by the presence of alpha
      fragment. These results suggest that the furin-processed alpha-fragment is
      involved in cellular signaling.

PMID- 16882676
TI  - Comparison of segmental and global markers of dyssynchrony in predicting clinical
      response to cardiac resynchronization.
AB  - AIMS: Cardiac resynchronization therapy (CRT) reduces inter- and intraventricular
      dyssynchrony and shortens total isovolumic time (t-IVT). We compared the extent
      to which the values of ventricular dyssynchrony and t-IVT predict clinical
      benefits of CRT. METHODS AND RESULTS: Ventricular dyssynchrony was assessed in 39
      patients with heart failure before and 6 months after CRT. Segmental dyssynchrony
      was identified from time to onset and peak systolic velocity of wall motion. T
      IVT (s/min) was derived as [60-(total ejection time+total filling time)]. The
      difference between ventricular pre-ejection periods (D-PEP) was calculated.
      Outcome measures were fall in New York Heart Association (NYHA) class and
      increase in cardiac output (CO). Following CRT, NYHA class fell in 29/39
      patients, CO increased (by 1.0 L/min, P < 0.001), and intraventricular delay
      (Intra-VD), interventricular delay (Inter-VD), t-IVT, and D-PEP shortened (by 25
      ms, 72 ms, 6 s/min, and 38 ms, P < 0.01). NYHA class and CO were unchanged with
      CRT in 10/39, and Intra-VD, Inter-VD, t-IVT, and D-PEP lengthened (by 43 ms, 52
      ms, 7 s/min, and 35 ms, P < 0.05). Though univariate predictors of CO increment
      with CRT were Intra-VD, Inter-VD, t-IVT, and D-PEP, only pre-CRT values of CO (P
      < 0.001), t-IVT (P < 0.001), and D-PEP (P = 0.025) were independent. CONCLUSION:
      Global, rather than segmental, measures of ventricular dyssynchrony are powerful,
      independent predictors of clinical response to CRT.

PMID- 16882677
TI  - Sex-based short- and long-term survival in patients following complicated
      myocardial infarction.
AB  - AIMS: Mortality in women following an acute myocardial infarction (AMI) is higher
      than in men, in that women are older and have more co-morbidity at the time of
      AMI. We evaluated short- and long-term sex-related differences in management and
      prognosis among high-risk patients following AMI. METHODS AND RESULTS: A total of
      1575 women and 3902 men with AMI and heart failure, left ventricular dysfunction,
      or anterior Q waves, were recruited for participation in the OPTIMAAL trial and
      followed for 2.7+/-0.9 years in seven European countries. Symptomatic heart
      failure was more common in women when compared with men. Women were older, with
      more hypertension and diabetes mellitus. Fewer women were treated with
      thrombolytics (P<0.001 in all cases). Women had a 1.37-fold higher risks of death
      (P<0.001) during follow-up, but no differences were observed after adjusting for
      age. However, in-hospital mortality was significantly higher in women (4.89 vs.
      2.54%; P<0.001) and a 1.57-fold higher risk of in-hospital death (P=0.006)
      persisted after adjusting for age and co-morbidities. CONCLUSION: Among high-risk
      patients with AMI, age-adjusted long-term survival was similar between sexes.
      However, adjusted in-hospital mortality was significantly higher in women. Higher
      short-term risk may warrant more rapid and appropriate management of women with
      AMI.

PMID- 16882678
TI  - Coenzyme Q10 and exercise training in chronic heart failure.
AB  - AIMS: There is evidence that plasma coenzyme Q(10) (CoQ(10)) levels decrease in
      patients with advanced chronic heart failure (CHF). However, it is not known
      whether oral CoQ(10) supplementation may improve cardiocirculatory efficiency and
      endothelial function in patients with CHF. METHODS AND RESULTS: We studied 23
      patients in NYHA class II and III (20 men, three women, mean age 59+/-9 years)
      with stable CHF secondary to ischaemic heart disease [ejection fraction 37+/-7%],
      using a double-blind, placebo-controlled cross-over design. Patients were
      assigned to each of the following treatments: oral CoQ(10) (100 mg tid), CoQ(10)
      plus supervised exercise training (ET) (60% of peak VO(2), five times a week),
      placebo, and placebo plus ET. Each phase lasted 4 weeks. Both peak VO(2) and
      endothelium-dependent dilation of the brachial artery (EDDBA) improved
      significantly after CoQ(10) and after ET as compared with placebo. CoQ(10) main
      effect was: peak VO(2)+9%, EDDBA +38%, systolic wall thickening score index
      (SWTI) -12%; ET produced comparable effects. CoQ(10) supplementation resulted in
      a four-fold increase in plasma CoQ(10) level, whereas the combination with ET
      further increased it. No side effects were reported with CoQ(10). CONCLUSIONS:
      Oral CoQ(10) improves functional capacity, endothelial function, and LV
      contractility in CHF without any side effects. The combination of CoQ(10) and ET
      resulted in higher plasma CoQ(10) levels and more pronounced effects on all the
      abovementioned parameters. However, significant synergistic effect of CoQ(10)
      with ET was observed only for peak SWTI suggesting that ET amplifies the already
      described effect of CoQ(10) on contractility of dysfunctional myocardium.

PMID- 16882679
TI  - Electrocardiographic risk stratification in families with congenital long QT
      syndrome.
AB  - AIMS: The QT interval in the surface ECG is one of the most often used risk
      stratifiers in families with congenital long QT syndrome (LQTS). The best ECG
      lead for clinical management of LQTS families remains unclear. METHODS AND
      RESULTS: The predictive power of the QTc interval in all ECG leads was studied in
      200 consecutive genotyped LQTS family members to identify mutation carriers (n =
      103; age: 35+/-19 years) and high-risk LQTS patients (n = 16 with survived sudden
      cardiac arrest) using receiver operating curve (ROC) analysis (ROC = area under
      curve). Additionally, the risk for events (syncope and sudden cardiac arrest) was
      calculated for QTc decile in all individuals. The predictive power was highest in
      lead II and lead V5 for identifying carriers in LQTS families. These ECG leads
      were optimal for risk stratification (ROC range 0.83-0.87). In these leads,
      positive predictive value (PPV) and negative predictive value (NPV) were highest
      for suggested QTc cut-offs (440 and 500 ms) for identification of LQTS mutation
      carriers and high-risk patients (PPV between 78-81 and 73-80%, respectively). The
      risk for events in QTc deciles increased exponentially from 10 to 80% and was 40%
      for QTc > 500 ms. CONCLUSION: On the basis of these data, QTc is the best
      diagnostic and prognostic ECG parameter in LQTS families. A single measurement
      should be obtained in lead II if measurable and then in left precordial leads
      (preferably V5) as a second choice.

PMID- 16882680
TI  - Effect of physical training on ventricular repolarization in type 1 long QT
      syndrome: a pilot study in asymptomatic carriers of the G589D KCNQ1 mutation.
AB  - AIMS: High-intensity physical exercise and competitive sports have been
      traditionally avoided in long QT syndrome. However, endurance training increases
      vagal activity and thus may improve cardiac electrical stability in healthy
      subjects. We hypothesized that controlled submaximal endurance training would not
      adversely affect ventricular repolarization in asymptomatic carriers of a KCNQ1
      gene mutation of type 1 long QT syndrome (LQT1). METHODS AND RESULTS: Previously,
      sedentary carriers of a missense mutation of KCNQ1 gene (LQT1, n=7) and healthy
      controls (n=8) exercised on a bicycle ergometer 3-4 times a week, 30 min a day at
      60-75% of maximal heart rate (HR) for a maximum of 3 months. Body surface
      potential mapping (BSPM) was recorded and QT intervals were determined
      automatically from 14 channels over the left chest area. Maximal work capacity
      increased by 4+/-1% in LQT1 and by 14+/-2% in controls (both P<0.05), and left
      ventricular (LV) mass by 8+/-1% and 9+/-1%, respectively (P<0.05). Resting
      corrected QT interval shortened by 10+/-1% (P<0.05) and QT interval dispersion by
      25+/-9% (P<0.05) in LQT1, but not significantly in controls. QT intervals at
      specified HRs during workload and recovery phases were not changed in either
      group. CONCLUSION: In this pilot study of asymptomatic carriers of a KNCQ1 gene
      mutation, submaximal endurance training did not harmfully affect arrhythmia risk
      markers. Confirmatory studies in a broader spectrum of LQT1 genotypes are needed
      before any generalization can be made.

PMID- 16882681
TI  - A reappraisal of the role of abscisic acid and its interaction with auxin in
      apical dominance.
AB  - BACKGROUND AND AIMS: Evidence from pea rms1, Arabidopsis max4 and petunia dad1
      mutant studies suggest an unidentified carotenoid-derived/plastid-produced
      branching inhibitor which moves acropetally from the roots to the shoots and
      interacts with auxin in the control of apical dominance. Since the plant hormone,
      abscisic acid (ABA), known to inhibit some growth processes, is also carotenoid
      derived/plastid produced, and because there has been indirect evidence for its
      involvement with branching, a re-examination of the role of ABA in apical
      dominance is timely. Even though it has been determined that ABA probably is not
      the second messenger for auxin in apical dominance and is not the above-mentioned
      unidentified branching inhibitor, the similarity of their derivation suggests
      possible relationships and/or interactions. METHODS: The classic Thimann-Skoog
      auxin replacement test for apical dominance with auxin [0.5 % naphthalene acetic
      acid (NAA)] applied both apically and basally was combined in similar treatments
      with 1 % ABA in Ipomoea nil (Japanese Morning Glory), Solanum lycopersicum
      (Better Boy tomato) and Helianthus annuus (Mammoth Grey-striped Sunflower). KEY
      RESULTS: Auxin, apically applied to the cut stem surface of decapitated shoots,
      strongly restored apical dominance in all three species, whereas the similar
      treatment with ABA did not. However, when ABA was applied basally, i.e. below the
      lateral bud of interest, there was a significant moderate repression of its
      outgrowth in Ipomoea and Solanum. There was also some additive repression when
      apical auxin and basal ABA treatments were combined in Ipomoea. CONCLUSION: The
      finding that basally applied ABA is able partially to restore apical dominance
      via acropetal transport up the shoot suggests possible interactions between ABA,
      auxin and the unidentified carotenoid-derived branching inhibitor that justify
      further investigation.

PMID- 16882682
TI  - Associative encoding in posterior piriform cortex during odor discrimination and
      reversal learning.
AB  - Recent proposals have conceptualized piriform cortex as an association cortex,
      capable of integrating incoming olfactory information with descending input from
      higher order associative regions such as orbitofrontal cortex and basolateral
      amygdala (ABL). If true, encoding in piriform cortex should reflect associative
      features prominent in these areas during associative learning involving olfactory
      cues. We recently reported that neurons in anterior piriform cortex (APC) in rats
      exhibited significant plasticity in their responses to odor cues during
      associative learning. Here, we have repeated this study, recording from neurons
      in posterior piriform cortex (PPC), a region of piriform cortex that receives
      much stronger input from ABL. If associative encoding in piriform cortex is
      driven by inputs from ABL, then we should see more plasticity in PPC neurons than
      we observed in APC. Consistent with this hypothesis, we found that PPC neurons
      were highly associative and appeared to be somewhat more likely than neurons
      recorded in APC to alter their responses to the odor cues after reversal of the
      odor-outcome associations in the task. Further, odor-selective PPC populations
      exhibited markedly different firing patterns based on the valence of the odor
      cue. These results suggest associative encoding in piriform cortex is represented
      in a topographical fashion, reflecting the stronger and more specific input from
      olfactory bulb concerning the sensory features of odors in anterior regions and
      stronger input from ABL concerning the meaning of odors in posterior regions.

PMID- 16882683
TI  - A meta-analysis of the diagnostic performance of the direct agglutination test
      and rK39 dipstick for visceral leishmaniasis.
AB  - OBJECTIVE: To compare the performance of the direct agglutination test and rK39
      dipstick for the diagnosis of visceral leishmaniasis. DATA SOURCES: Medline,
      citation tracking, January 1986 to December 2004. Selection criteria Original
      studies evaluating the direct agglutination test or the rK39 dipstick with
      clinical visceral leishmaniasis as target condition; adequate reference
      classification; and absolute numbers of true positive, true negative, false
      positive, and false negative observations available or derivable from the data
      presented. RESULTS: 30 studies evaluating the direct agglutination test and 13
      studies evaluating the rK39 dipstick met the inclusion criteria. The combined
      sensitivity estimates of the direct agglutination test and the rK39 dipstick were
      94.8% (95% confidence interval 92.7% to 96.4%) and 93.9% (87.7% to 97.1%),
      respectively. Sensitivity seemed higher and more homogenous in the studies
      carried out in South Asia. Specificity estimates were influenced by the type of
      controls. In phase III studies carried out on patients with clinically suspected
      disease, the estimated specificity of the direct agglutination test was 85.9%
      (72.3% to 93.4%) and of the rK39 dipstick was 90.6% (66.8% to 97.9%). CONCLUSION:
      The diagnostic performance of the direct agglutination test and the rK39 dipstick
      for visceral leishmaniasis is good to excellent and seem comparable.

PMID- 16882684
TI  - Intranasal lidocaine 8% spray for second-division trigeminal neuralgia.
AB  - BACKGROUND: Trigeminal nerve block has been widely used for trigeminal neuralgia.
      This may induce paraesthesia. The second division of the trigeminal nerve passes
      through the sphenopalatine ganglion, which is located posterior to the middle
      turbinate and is covered by a mucous membrane. We examined the effectiveness of
      intranasal lidocaine 8% spray on paroxysmal pain in second-division trigeminal
      neuralgia. METHODS: Twenty-five patients with second-division trigeminal
      neuralgia were randomized to receive two sprays (0.2 ml) of either lidocaine 8%
      or saline placebo in the affected nostril using a metered-dose spray. After a 7
      day period, patients were crossed over to receive the alternative treatment. The
      paroxysmal pain triggered by touching or moving face was assessed with a 10 cm
      visual analogue scale (VAS) before and 15 min after treatment. Patients used a
      descriptive scale to grade pain outcome, and were asked to note whether the pain
      returned and how long after therapy it recurred. RESULTS: Intranasal lidocaine 8%
      spray significantly decreased VAS [baseline: 8.0 (2.0) cm, 15 min postspray: 1.5
      (1.9) cm, mean (SD)], whereas the placebo spray did not [7.9 (2.0) cm, 7.6 (2.0)
      cm]. Moreover, pain was described as moderate or better by 23 patients of the
      lidocaine spray and 1 of the placebo group. The effect of treatment persisted for
      4.3 h (range 0.5-24 h). CONCLUSIONS: Intranasal lidocaine 8% administered by a
      metered-dose spray produced prompt but temporary analgesia without serious
      adverse reactions in patients with second-division trigeminal neuralgia.

PMID- 16882685
TI  - Water equivalent plastic scintillation detectors in radiation therapy.
AB  - A review of the dosimetric characteristics and properties of plastic
      scintillation detectors for use in radiation therapy is presented. The detectors
      show many desirable qualities when exposed to megavoltage photon and electron
      beams, including water equivalence, energy independence, reproducibility, dose
      linearity, resistance to radiation damage and near temperature independence.
      These detectors do not require the usual conversion and/or correction factors
      used to convert the readings from common dosemeters to absorbed dose. Due to
      their small detecting volume, plastic scintillation detectors exhibit excellent
      spatial resolution. Detector performance, in certain specific cases, can be
      affected by radiation-induced light arising in the optical fibres that carry the
      scintillator signal to a photodetector. While this effect is negligible for
      photon beams, it may not be ignored for electron beams and needs to be accounted
      for.

PMID- 16882686
TI  - Who failed to enroll in Medicare Part D, and why? Early results.
AB  - Early results on the Medicare Part D prescription drug program, from a survey of
      people age sixty-five and older who were interviewed just before enrollment
      started and just after it ended, indicate that Medicare has met its target of 90
      percent coverage. Enrollment rates in vulnerable subpopulations-poor health, low
      income, or cognitive impairment-are almost high enough to offset lower rates of
      other coverage. However, sizable numbers of elderly people remain uncovered,
      contrary to their self-interest. Seniors give Part D mixed reviews, and
      majorities are less satisfied with Medicare and with the government as a result
      of their experience with this program.

PMID- 16882687
TI  - Analysis of Connexin43 phosphorylated at S325, S328 and S330 in normoxic and
      ischemic heart.
AB  - The functional consequences of Connexin43 (Cx43) phosphorylation remain largely
      unexplored. Using an antibody that specifically recognizes Cx43 phosphorylated at
      serine residues 325, 328 and/or 330 (pS325/328/330-Cx43), we show that labeling
      of this form of Cx43 as well as of total Cx43 is restricted to the intercalated
      disk region of normal ventricular tissue. In ischemic heart, significant
      relocalization of total Cx43 to the lateral edges of myocytes was evident;
      however pS325/328/330-Cx43 remained predominately at the intercalated disk.
      Western blots indicated a eightfold decrease in pS325/328/330-Cx43 in ischemic
      tissue. Peptide-binding- and competition-experiments indicated that our antibody
      mainly detected Cx43 phosphorylated at S328 and/or S330 in heart tissue. To
      evaluate how this change in Cx43 phosphorylation contributes to ischemia-induced
      downregulation of intercellular communication, we stably transfected Cx43(-/-)
      cells with a Cx43 construct in which serine residues 325, 328 and 330 had been
      mutated to alanine (Cx43-TM). Cx43-TM was not efficiently processed to isoforms
      that have been correlated with gap junction assembly. Nevertheless, Cx43-TM cells
      were electrically coupled, although development of coupling was delayed. Fully
      opened channels were only rarely observed in Cx43-TM cells, and Lucifer-Yellow
      dye-coupling was significantly reduced compared with wild-type cells. These data
      suggest that phosphorylation of Cx43 at serine residues 325, 328 and/or 330
      influences channel permselectivity and regulates the efficiency of gap junction
      assembly.

PMID- 16882688
TI  - centrosomin's beautiful sister (cbs) encodes a GRIP-domain protein that marks
      Golgi inheritance and functions in the centrosome cycle in Drosophila.
AB  - The mechanism of inheritance of the Golgi complex is an important problem in cell
      biology. In this study, we examine the localization and function of a Golgi
      protein encoded by centrosomin's beautiful sister (cbs) during cleavage in
      Drosophila melanogaster. Cbs contains a GRIP domain that is 57% identical to
      vertebrate Golgin-97. Cbs undergoes a dramatic relocalization during mitosis from
      the cytoplasm to an association with chromosomes from late prometaphase to early
      telophase, by a transport mechanism that requires the GRIP domain and Arl1, the
      product of the Arf72A locus. Additionally, Cbs remains independent of the
      endoplasmic reticulum throughout cleavage. The use of RNAi, Arf72A mutant
      analysis and ectopic expression of the GRIP domain, shows that cycling of Cbs
      during mitosis is required for the centrosome cycle. The effects on the
      centrosome cycle depend on Cbs concentration and Cbs transport from the cytoplasm
      to DNA. When Cbs levels are reduced centrosomes fail to mature, and when Cbs
      transport is impeded by ectopic expression of the GRIP domain, centrosomes
      undergo hypertrophy. We propose that, Cbs is a trans-Golgi protein that links
      Golgi inheritance to the cell cycle and the Drosophila Golgi is more vertebrate
      like than previously recognized.

PMID- 16882689
TI  - Cell and fibronectin dynamics during branching morphogenesis.
AB  - Branching morphogenesis is a dynamic developmental process shared by many organs,
      but the mechanisms that reorganize cells during branching morphogenesis are not
      well understood. We hypothesized that extensive cell rearrangements are involved,
      and investigated cell migration using two-color confocal time-lapse microscopy to
      image cell and extracellular-matrix dynamics in developing salivary glands. We
      labeled submandibular salivary gland (SMG) epithelial cells with green
      fluorescent protein and matrix with fluorescent fibronectin. Surprisingly, we
      observed substantial, rapid and relatively random migration of individual
      epithelial cells during branching morphogenesis. We predicted that cell migration
      would decrease after formation of acini and, indeed, found that rapid cell
      movements do not occur in SMG from newborn mice. However, in embryonic SMG
      epithelial cells, we observed an absence of choreographed cell migration,
      indicating that patterned cell migration alone cannot explain the highly ordered
      process of branching morphogenesis. We therefore hypothesized a role for
      directional fibronection assembly in branching. Washout and pulse-chase
      experiments revealed that older fibronectin accumulates at the base of the clefts
      and translocates inwards as a wedge, with newer fibronectin assembling behind it.
      These findings identify a new mechanism for branching morphogenesis involving
      directional fibronectin translocation superimposed on individual cell dynamics.

PMID- 16882690
TI  - Conserved and specific functions of axoneme components in trypanosome motility.
AB  - The Trypanosoma brucei flagellum is unusual as it is attached along the cell body
      and contains, in addition to an apparently conventional axoneme, a structure
      called the paraflagellar rod, which is essential for cell motility. Here, we
      investigated flagellum behaviour in normal and mutant trypanosome cell lines
      where expression of genes encoding various axoneme proteins (PF16, PF20, DNAI1,
      LC2) had been silenced by RNAi. First, we show that the propulsive wave (normally
      used for forward motility) is abolished in the absence of outer dynein arms,
      whereas the reverse wave (normally used for changing direction) still occurs.
      Second, in contrast to Chlamydomonas--but like metazoa, the central pair adopts a
      fixed orientation during flagellum beating. This orientation becomes highly
      variable in central-pair- and outer-dynein-arm-mutants. Third, the paraflagellar
      rod contributes to motility by facilitating three-dimensional wave propagation
      and controlling cell shape. Fourth, motility is required to complete the last
      stage of cell division in both insect and bloodstream stages of the parasite.
      Finally, our study also reveals the conservation of molecular components of the
      trypanosome flagellum. Coupled to the ease of reverse genetics, it raises the
      interest of trypanosomes as model organisms to study cilia and flagella.

PMID- 16882691
TI  - Inositol 1,4,5-trisphosphate supports the arrhythmogenic action of endothelin-1
      on ventricular cardiac myocytes.
AB  - Although ventricular cardiomyocytes express inositol 1,4,5-trisphosphate
      [Ins(1,4,5)P3] receptors, it is unclear how these Ca2+ channels contribute to the
      effects of Gq-coupled agonists. Endothelin-1 augmented the amplitude of pacing
      evoked Ca2+ signals (positive inotropy), and caused an increasing frequency of
      spontaneous diastolic Ca2+-release transients. Both effects of endothelin-1 were
      blocked by an antagonist of phospholipase C, suggesting that Ins(1,4,5)P3 and/or
      diacylglycerol production was necessary. The endothelin-1-mediated spontaneous
      Ca2+ transients were abolished by application of 2-aminoethoxydiphenyl borate (2
      APB), an antagonist of Ins(1,4,5)P3 receptors. Incubation of electrically-paced
      ventricular myocytes with a membrane-permeant Ins(1,4,5)P3 ester provoked the
      occurrence of spontaneous diastolic Ca2+ transients with the same characteristics
      and sensitivity to 2-APB as the events stimulated by endothelin-1. In addition to
      evoking spontaneous Ca2+ transients, stimulation of ventricular myocytes with the
      Ins(1,4,5)P3 ester caused a positive inotropic effect. The effects of endothelin
      1 were compared with two other stimuli, isoproterenol and digoxin, which are
      known to induce inotropy and spontaneous Ca2+ transients by overloading
      intracellular Ca2+ stores. The events evoked by isoproterenol and digoxin were
      dissimilar from those triggered by endothelin-1 in several ways. We propose that
      Ins(1,4,5)P3 receptors support the development of both inotropy and spontaneous
      pro-arrhythmic Ca2+ signals in ventricular myocytes stimulated with a Gq-coupled
      agonist.

PMID- 16882692
TI  - Casein kinase 2 inhibition decreases hypoxia-inducible factor-1 activity under
      hypoxia through elevated p53 protein level.
AB  - HIF-1 (hypoxia-inducible factor-1) is the main transcription factor involved in
      the adaptation of cells to hypoxia. In addition to regulation of HIF-1alpha
      protein level, HIF-1 activity is also enhanced by several pathways involving
      asparagine hydroxylation and phosphorylation. Here, we investigated the
      relationship between casein kinase 2 (CK2), p53 and HIF-1. An increase in p53
      protein level and transcriptional activity was observed when CK2 was inhibited by
      different inhibitors under normoxia and hypoxia. This increase was in parallel
      with a decrease in HIF-1 activity without changes in HIF-1alpha protein level,
      indicating a regulation of its transcriptional activity. Similar results were
      obtained using CK2alpha siRNA. Ectopic overexpression of p53 also led to an
      inhibition of HIF-1 activity. Conversely, CK2 inhibition had no effect in p53
      null cells indicating that the inhibitory effect of CK2 inhibitors requires the
      presence of p53. p53 activity was not required because overexpression of a p53
      mutated in its DNA-binding domain exerted the same effect as wild-type p53 and
      because the effect of CK2 inhibitors was still observed when p53 activity was
      inhibited by pifithrin-alpha. Since CK2 activity is increased in hypoxic
      conditions, this process provides one more mechanism to ensure enhanced HIF-1
      activity under such conditions.

PMID- 16882693
TI  - Activation of urokinase receptor by a novel interaction between the connecting
      peptide region of urokinase and alpha v beta 5 integrin.
AB  - The serine protease urokinase (uPA) binds to the urokinase receptor (uPAR)
      through its growth-factor domain (GFD, residues 1-49), affecting cell migration,
      adhesion and growth. Here, we show that uPA can promote cytoskeletal
      rearrangements and directional cell migration in a GFD-independent manner,
      through a new and specific interaction between an internal uPA domain coined
      ;connecting peptide' (residues 132-158) and cell-surface integrin alpha v beta 5.
      Remarkably, a peptide corresponding to this region (CPp, residues 135-158)
      retains the ability to bind to alpha v beta 5, eliciting cytoskeletal
      rearrangements and directing cell migration at a concentration as low as 1-10 pM.
      These effects are lost in cells not expressing uPAR, indicating that the uPAR is
      required for CPp-dependent signaling. Furthermore, the CPp-alpha v beta 5
      integrin interaction enhances F-actin-enriched protrusions and cell migration
      induced by the well-established interaction between the uPAR-binding peptide
      (GFDp, residues 12-32) of uPA and uPAR. These results provide new insight into
      the function of uPA, which--through individual domains--can engage two different
      surface receptors (uPAR and alpha v beta 5 integrin), thus initiating and
      potentiating intracellular signaling and migration.

PMID- 16882694
TI  - Regulation of epithelial wound closure and intercellular adhesion by interaction
      of AF6 with actin cytoskeleton.
AB  - AF6 is a human multi-domain protein involved in signaling and organization of
      cell junctions during embryogenesis. Its homologue in rat is called afadin. Three
      different AF6 transcripts are known, but only isoform 1 (AF6i1) has been
      characterized as protein. We focused on the AF6 isoform 3 (AF6i3), which differs
      from the AF6i1 by an additional C-terminal F-actin-binding site. Knockdown of
      AF6i3 in epithelial cells, which express only this isoform, resulted in impaired
      E-cadherin-dependent intercellular adhesion due to concomitantly reduced
      association of E-cadherin with F-actin and p120-catenin. Impaired intercellular
      adhesion also accelerated wound closure due to increased directionality of cell
      migration and delayed de novo formation of cell junctions. In contrast to AF6i3,
      the AF6i1 displayed a reduced association with the actin cytoskeleton and did not
      stabilize intercellular adhesion. Therefore, we propose that the AF6i3 protein
      stabilizes E-cadherin-dependent adhesion during dynamic processes, such as wound
      closure and formation of cell junctions, by linking the E-cadherin-catenin
      complex to the actin cytoskeleton via its F-actin-binding site.

PMID- 16882695
TI  - Skin adnexal neoplasms--part 2: an approach to tumours of cutaneous sweat glands.
AB  - Tumours of cutaneous sweat glands are uncommon, with a wide histological
      spectrum, complex classification and many different terms often used to describe
      the same tumour. Furthermore, many eccrine/apocrine lesions coexist within
      hamartomas or within lesions with composite/mixed differentiation. In addition to
      the eccrine and apocrine glands, two other skin sweat glands have recently been
      described: the apoeccrine and the mammary-like glands of the anogenital area. In
      this review (the second of two articles on skin adnexal neoplasms), common as
      well as important benign and malignant lesions of cutaneous sweat glands are
      described, and a summary for differentiating primary adnexal neoplasms from
      metastatic carcinoma is outlined, striving to maintain a common and acceptable
      terminology in this complex subject. Composite/mixed adnexal tumours are also
      discussed briefly.

PMID- 16882696
TI  - Skin adnexal neoplasms--part 1: an approach to tumours of the pilosebaceous unit.
AB  - Skin adnexal neoplasms comprise a wide spectrum of benign and malignant tumours
      that exhibit morphological differentiation towards one or more types of adnexal
      structures found in normal skin. Most adnexal neoplasms are relatively uncommonly
      encountered in routine practice, and pathologists can recognise a limited number
      of frequently encountered tumours. In this review, the first of two, the normal
      histology of the skin adnexal structures is reviewed, and the histological
      features of selected but important benign and malignant tumours and tumour-like
      lesions of pilosebaceous origin discussed, with emphasis on the diagnostic
      approach and pitfalls in histological diagnosis.

PMID- 16882699
TI  - HER2, TOP2A, CCND1, EGFR and C-MYC oncogene amplification in colorectal cancer.
AB  - AIM: Recent studies had suggested substantial molecular differences between
      tumours from different ethnic groups. In this study, the molecular differences
      between the incidences of colorectal carcinoma in Saudi and Swiss populations are
      investigated. METHOD: 518 cases of colon cancer tumours (114 from Saudi Arabia
      and 404 from Switzerland) were analysed in a tissue microarray format.
      Fluorescence in situ hybridisation (FISH) was used to estimate frequencies of
      copy number changes of known oncogenes, including HER2, TOPO2A, CCND1, EGFR and C
      MYC. RESULTS: Using FISH, amplifications were mostly low level (gene-to
      centromere ratio 2 to 4), which is in contrast with other tumour types with more
      frequent gene amplifications. The amplifications were particularly frequent for
      MYC (Saudi 9% and Swiss 14.2%) but unrelated to clinical outcome and pathological
      information. Remarkably, there were four tumours exhibiting classic high-level
      gene amplification for HER2 (Swiss 1.3%), a pattern often accompanied by response
      to trastuzumab (Herceptin) in breast cancer. Occasional high-level amplifications
      were also observed for CCND1 (Saudi 1/106, 0.9%; Swiss 2/373, 0.5%) and EGFR
      (Swiss 2/355; 0.6%). CONCLUSIONS: Rare high-level amplifications of therapeutic
      target genes were found in patients with colon cancer. Although no molecular
      differences were found between incidences of colon cancer cases in Swiss and
      Saudi populations, these observations emphasise the urgent need for clinical
      studies investigating the effect of targeted therapies.

PMID- 16882698
TI  - Squamous differentiation in primary urothelial carcinoma of the urinary tract as
      seen by MAC387 immunohistochemistry.
AB  - Squamous differentiation (SqD) is variably present in urinary tract tumours, but
      its significance remains unclear. In this study, SqD was assessed by
      immunohistochemistry using the monoclonal antibody Mac387 in 145 urothelial
      tumours (bladder, n = 115; renal pelvis, n = 30). Mac387 detects the
      myelomonocytic L1 antigen; a member of the calgranulin family shared by
      epithelial cells and keratinocytes. L1 antigen was shown in SqD in urothelial
      carcinomas of the bladder or the renal pelvis, including 11 cases with focal SqD
      unrecognised by conventional analysis. SqD is more frequent in renal pelvic
      tumours (p = 0.027) and increases with grade/stage mainly in bladder carcinoma
      (grade, p = 0.05; stage, p = 0.005). Stage Ta/T1 bladder carcinomas with SqD
      recurred more (p = 0.021). In conclusion, Mac387 efficiently shows SqD in
      urothelial tumours.

PMID- 16882697
TI  - Expression of nuclear insulin receptor substrate 1 in breast cancer.
AB  - BACKGROUND: Insulin receptor substrate 1 (IRS-1), a cytoplasmic protein
      transmitting signals from the insulin and insulin-like growth factor 1 receptors,
      has been implicated in breast cancer. Previously, it was reported that IRS-1 can
      be translocated to the nucleus and modulate oestrogen receptor alpha (ERalpha)
      activity in vitro. However, the expression of nuclear IRS-1 in breast cancer
      biopsy specimens has never been examined. AIMS: To assess whether nuclear IRS-1
      is present in breast cancer and non-cancer mammary epithelium, and whether it
      correlates with other markers, especially ERalpha. Parallel studies were carried
      out for the expression of cytoplasmatic IRS-1. METHODS: IRS-1 and ERalpha
      expression was assessed by immunohistochemical analysis. Data were evaluated
      using Pearson's correlation, linear regression and receiver operating
      characteristic analysis. RESULTS: Median nuclear IRS-1 expression was found to be
      low in normal mammary epithelial cells (1.6%) and high in benign tumours (20.5%),
      ductal grade 2 carcinoma (11.0%) and lobular carcinoma (approximately 30%).
      Median ERalpha expression in normal epithelium, benign tumours, ductal cancer
      grade 2 and 3, and lobular cancer grade 2 and 3 were 10.5, 20.5, 65.0, 0.0, 80
      and 15%, respectively. Nuclear IRS-1 and ERalpha positively correlated in ductal
      cancer (p<0.001) and benign tumours (p<0.01), but were not associated in lobular
      cancer and normal mammary epithelium. In ductal carcinoma, both nuclear IRS-1 and
      ERalpha negatively correlated with tumour grade, size, mitotic index and lymph
      node involvement. Cytoplasmic IRS-1 was expressed in all specimens and positively
      correlated with ERalpha in ductal cancer. CONCLUSIONS: A positive association
      between nuclear IRS-1 and ERalpha is a characteristic for ductal breast cancer
      and marks a more differentiated, non-metastatic phenotype.

PMID- 16882700
TI  - Examination of breast needle core biopsy specimens performed for screen-detected
      microcalcification.
AB  - AIMS: To establish the number of histological levels necessary for the evaluation
      of breast needle core biopsy (NCB) specimens taken from areas of mammographic
      calcification in patients presenting via the UK National Health Service Breast
      Screening Programme. METHODS: Retrospective review of a series of breast NCB
      specimens initially examined routinely at nine levels. The presence of
      calcification within the histological sections in each of three sets of levels
      (levels 1-3, 4-6 and 7-9) and the (cumulative) diagnostic B category that would
      have pertained after each were assessed. RESULTS: Accurate diagnostic
      classification was possible after examination of three levels in 89% cases.
      Examination of a further three levels permitted accurate diagnosis in a further
      eight cases (total 97% cases). In only three cases were nine levels necessary for
      accurate classification. In only a single case (1%) was it likely that routine
      examination of six levels could have led to significant misclassification. In a
      significant group of patients (18%), nine levels were considered to provide
      additional useful information, although this information did not alter the
      diagnosis. CONCLUSIONS: NCBs for screen-detected mammographic calcification
      should be routinely examined at six levels. Further levels may be needed in
      occasional cases to identify more conclusively the associated pathological
      abnormality. Further levels may be of particular value when assessing atypical
      intraductal proliferative epithelial lesions.

PMID- 16882701
TI  - The evolutionary origin of Xanthomonadales genomes and the nature of the
      horizontal gene transfer process.
AB  - Determining the influence of horizontal gene transfer (HGT) on phylogenomic
      analyses and the retrieval of a tree of life is relevant for our understanding of
      microbial genome evolution. It is particularly difficult to differentiate between
      phylogenetic incongruence due to noise and that resulting from HGT. We have
      performed a large-scale, detailed evolutionary analysis of the different
      phylogenetic signals present in the genomes of Xanthomonadales, a group of
      Proteobacteria. We show that the presence of phylogenetic noise is not an
      obstacle to infer past and present HGTs during their evolution. The scenario
      derived from this analysis and other recently published reports reflect the
      confounding effects on bacterial phylogenomics of past and present HGT. Although
      transfers between closely related species are difficult to detect in genome-scale
      phylogenetic analyses, past transfers to the ancestor of extant groups appear as
      conflicting signals that occasionally might make impossible to determine the
      evolutionary origin of the whole genome.

PMID- 16882702
TI  - Towards a better understanding of RNA carriage by ejaculate spermatozoa.
AB  - Research on spermatozoal RNA has made considerable progress since the original
      reports on its presence appeared in the late 1950s and early 1960s. Through the
      use of stringent procedures aimed at eliminating contamination artefacts, we now
      appreciate that a complex cohort of mRNAs persists in the ejaculate cell but that
      80S (cytoplasmic) ribosomal complexes are not present in sufficient quantities to
      support cytoplasmic mRNA translation. Despite this, under certain conditions, at
      least some cytoplasmic mRNAs can apparently be translated de novo, possibly on
      mitochondrial polysomes. The detection of mRNA translation by mature spermatozoa
      essentially supports the earliest research reports on spermatozoal gene
      expression although the suggested relationship with protein turnover and
      capacitation is wholly unexpected. We also examine some alternative explanations
      and roles for RNA carriage, including the RNAs passive retention as a consequence
      of nuclear shutdown and a more active role in chromatin repackaging, genomic
      imprinting, gene silencing and post-fertilization requirements of essential
      paternal RNAs. The recent report of an RNA-mediated epigenetic alteration to
      phenotype that is likely to be sperm derived is of particular interest in this
      regard. We finally show that regardless of the biological role(s) of spermatozoal
      RNA, its utility in infertility studies, particularly when coupled with modern
      techniques in gene-expression analysis (e.g. microarrays), is obvious. As a
      wholly non-invasive proxy for the testis, this RNA offers considerable potential
      as a marker for fertility status and the genetic and environmental influences
      that could make all the difference between a fertile and an infertile phenotype.

PMID- 16882703
TI  - Occupational paraffin-induced pulmonary fibrosis: a 25-year follow-up.
AB  - Exogenous lipid pneumonia can exceptionally be caused by occupational exposure to
      paraffin. The authors report a case of severe interstitial pulmonary disease
      induced by occupational exposure to paraffin, leading to delayed fibrosis over a
      25-year follow-up, despite cessation of exposure.

PMID- 16882704
TI  - CTLA-4 dysregulation of self/tumor-reactive CD8+ T-cell function is CD4+ T-cell
      dependent.
AB  - Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) maintains peripheral
      tolerance by suppressing T-cell activation and proliferation but its precise role
      in vivo remains unclear. We sought to elucidate the impact of CTLA-4 expression
      on self/tumor-reactive CD8(+) T cells by using the glycoprotein (gp) 100-specific
      T-cell receptor (TCR) transgenic mouse, pmel-1. pmel-1 CLTA-4(-/-) mice developed
      profound, accelerated autoimmune vitiligo. This enhanced autoimmunity was
      associated with a small but highly activated CD8(+) T-cell population and large
      numbers of CD4(+) T cells not expressing the transgenic TCR. Adoptive transfer of
      pmel-1 CLTA-4(-/-) CD8(+) T cells did not mediate superior antitumor immunity in
      the settings of either large established tumors or tumor challenge, suggesting
      that the mere absence of CTLA-4-mediated inhibition on CD8(+) T cells did not
      directly promote enhancement of their effector functions. Removal of CD4(+) T
      cells by crossing the pmel-1 CLTA-4(-/-) mouse onto a Rag-1(-/-) background
      resulted in the complete abrogation of CD8(+) T-cell activation and autoimmune
      manifestations. The effects of CD4(+) CLTA-4(-/-) T cells were dependent on the
      absence of CTLA-4 on CD8(+) T cells. These results indicated that CD8(+) CLTA-4(
      /-) T-cell-mediated autoimmunity and tumor immunity required CD4(+) T cells in
      which the function was dysregulated by the absence of CTLA-4-mediated negative
      costimulation.

PMID- 16882705
TI  - Nef interference with HIV-1-specific CTL antiviral activity is epitope specific.
AB  - HIV-1 Nef and HIV-1-specific cytotoxic T lymphocytes (CTLs) have important and
      opposing roles in the immunopathogenesis of HIV-1 infection. Nef-mediated down
      modulation of HLA class I on infected cells can confer resistance to CTL
      clearance, but the factors determining the efficiency of this process are
      unknown. This study examines the impact of Nef on the antiviral activity of
      several CTL clones recognizing epitopes from early and late HIV-1 proteins,
      restricted by HLA-A, -B, and -C molecules. CTL-targeting epitopes in early
      proteins remained susceptible to the effects of Nef, although possibly to a
      lesser degree than CTL-targeting late protein epitopes, indicating that
      significant Nef-mediated HLA down-regulation can precede even the presentation of
      early protein-derived epitopes. However, HLA-C-restricted CTLs were unaffected by
      Nef, consistent with down-regulation of cell-surface HLA-A and -B but not HLA-C
      molecules. Thus, CTLs vary dramatically in their susceptibility to Nef
      interference, suggesting differences in the relative importance of HLA-A- and HLA
      B- versus HLA-C-restricted CTLs in vivo. The data thus indicate that HLA-C
      restricted CTLs may have an under-appreciated antiviral role in the setting of
      Nef in vivo and suggest a benefit of promoting HLA-C-restricted CTLs for
      immunotherapy or vaccine development.

PMID- 16882706
TI  - Suppression of hepcidin during anemia requires erythropoietic activity.
AB  - Hepcidin, the principal iron regulatory hormone, regulates the absorption of iron
      from the diet and the mobilization of iron from stores. Previous studies
      indicated that hepcidin is suppressed during anemia, a response that would
      appropriately increase the absorption of iron and its release from stores.
      Indeed, in the mouse model, hepcidin-1 was suppressed after phlebotomy or
      erythropoietin administration but the suppression was reversed by inhibitors of
      erythropoiesis. The suppression of hepcidin necessary to match iron supply to
      erythropoietic demand thus requires increased erythropoiesis and is not directly
      mediated by anemia, tissue hypoxia, or erythropoietin.

PMID- 16882707
TI  - Epstein-Barr virus nuclear antigen 2 inhibits AID expression during EBV-driven B
      cell growth.
AB  - Somatic hypermutation and class-switch recombination in germinal centers
      critically depend on activation-induced cytidine deaminase (AID). Deregulation of
      AID may lead to the aberrant activation or persistence of both genetic processes,
      thus contributing to the pathogenesis of B-cell lymphomas by mistargeted
      mutagenesis or recombination. The Epstein-Barr virus (EBV) establishes an
      asymptomatic latent infection in more than 90% of the human population, but it
      has also been linked to lymphomagenesis. A cooperative relationship of EBV and
      the germinal center reaction during the establishment of viral persistence has
      been postulated, but the contribution of EBV latent genes to the respective
      genetic events remains to be investigated in detail. In the present study, we
      show that activation of the EBV growth program has a clear inhibitory effect on
      AID expression, due to a negative effect of the master transcription factor of
      this program, EBNA2. This mechanism may counterbalance AID induction by the LMP1
      protein, in order to prevent deleterious genetic changes during EBV-induced B
      cell growth. EBNA2-mediated AID inhibition also provides a molecular explanation
      for the previously observed differences in somatic hypermutation activity in EBV
      associated lymphoproliferative diseases, thus pointing to a crucial mechanism of
      EBV-mediated regulation of genomic integrity.

PMID- 16882708
TI  - Results of a randomized study of 3 schedules of low-dose decitabine in higher
      risk myelodysplastic syndrome and chronic myelomonocytic leukemia.
AB  - Epigenetic therapy with hypomethylating drugs is now the standard of care in
      myelodysplastic syndrome (MDS). Response rates remain low, and mechanism-based
      dose optimization has not been reported. We investigated the clinical and
      pharmacodynamic results of different dose schedules of decitabine. Adults with
      advanced MDS or chronic myelomonocytic leukemia (CMML) were randomized to 1 of 3
      decitabine schedules: (1) 20 mg/m2 intravenously daily for 5 days; (2) 20 mg/m2
      subcutaneously daily for 5 days; and (3) 10 mg/m2 intravenously daily for 10
      days. Randomization followed a Bayesian adaptive design. Ninety-five patients
      were treated (77 with MDS, and 18 with CMML). Overall, 32 patients (34%) achieved
      a complete response (CR), and 69 (73%) had an objective response by the new
      modified International Working Group criteria. The 5-day intravenous schedule,
      which had the highest dose-intensity, was selected as optimal; the CR rate in
      that arm was 39%, compared with 21% in the 5-day subcutaneous arm and 24% in the
      10-day intravenous arm (P < .05). The high dose-intensity arm was also superior
      at inducing hypomethylation at day 5 and at activating P15 expression at days 12
      or 28 after therapy. We conclude that a low-dose, dose-intensity schedule of
      decitabine optimizes epigenetic modulation and clinical responses in MDS.

PMID- 16882709
TI  - Expression of interleukin-3 receptor subunits on defined subpopulations of acute
      myeloid leukemia blasts predicts the cytotoxicity of diphtheria toxin interleukin
      3 fusion protein against malignant progenitors that engraft in immunodeficient
      mice.
AB  - The interleukin-3 receptor (IL-3R) subunits are overexpressed on acute myeloid
      leukemia (AML) blasts compared with normal hematopoietic cells and are thus
      potential targets for novel therapeutic agents. Both fluorescence-activated cell
      sorter (FACS) analysis and quantitative real-time reverse transcription
      polymerase chain reaction (QRT-PCR) were used to quantify expression of the IL
      3Ralpha and beta(c) subunits on AML cells. QRT-PCR for both subunits was most
      predictive of killing of AML colony-forming cells (AML-CFCs) by diphtheria toxin
      IL-3 fusion protein (DT(388)IL3). Among 19 patient samples, the relative level of
      the IL-3Ralpha was higher than the IL-3Rbeta(c) and highest in CD34(+)CD38(
      )CD71(-) cells, enriched for candidate leukemia stem cells, compared with cell
      fractions depleted of such progenitors. Overall, the amount of IL-3Rbeta(c)
      subunit did not vary among sorted subpopulations. However, expression of both
      subunits varied by more than 10-fold among different AML samples for all
      subpopulations studied. The level of IL-3Rbeta(c) expression versus
      glyceraldehyde-3-phosphate dehydrogenase (GAPDH) (set at 1000) ranged from 0.14
      to 13.56 in CD34(+)CD38(-)CD71(-) cells from different samples; this value was
      correlated (r = .76, P = .05) with the ability of DT(388)IL3 to kill AML
      progenitors that engraft in beta(2)-microglobin-deficient nonobese
      diabetic/severe combined immunodeficient (NOD/SCID) mice (n = 7). Thus,
      quantification of IL-3R subunit expression on AML blasts predicts the
      effectiveness IL-3R-targeted therapy in killing primitive leukemic progenitors.

PMID- 16882710
TI  - Apoptotic cell thrombospondin-1 and heparin-binding domain lead to dendritic-cell
      phagocytic and tolerizing states.
AB  - Apoptotic cells were shown to induce dendritic cell immune tolerance. We applied
      a proteomic approach to identify molecules that are secreted from apoptotic
      monocytes, and thus may mediate engulfment and immune suppression. Supernatants
      of monocytes undergoing apoptosis were collected and compared using sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and differentially
      expressed proteins were identified using tandem mass spectrometry. Thrombospondin
      1 (TSP-1) and its cleaved 26-kDa heparin-binding domain (HBD) were identified. We
      show that TSP-1 is expressed upon induction of monocyte apoptosis in a caspase
      dependent pattern and the HBD is cleaved by chymotrypsin-like serine protease. We
      further show that CD29, CD36, CD47, CD51, and CD91 simultaneously participate in
      engulfment induction and generation of an immature dendritic cell (iDC)
      tolerogenic and phagocytic state. We conclude that apoptotic cell TSP-1, and
      notably its HBD, creates a signalosome in iDCs to improve engulfment and to
      tolerate engulfed material prior to the interaction with apoptotic cells.

PMID- 16882711
TI  - Phase 1/2 study of the combination of 5-aza-2'-deoxycytidine with valproic acid
      in patients with leukemia.
AB  - We conducted a phase 1/2 study of the combination of 5-aza-2'-deoxycytidine
      (decitabine) and the histone deacetylase inhibitor valproic acid (VPA) in
      patients with advanced leukemia, including older untreated patients. A group of
      54 patients were treated with a fixed dose of decitabine (15 mg/m(2) by IV daily
      for 10 days) administered concomitantly with escalating doses of VPA orally for
      10 days. A 50 mg/kg daily dose of VPA was found to be safe. Twelve (22%) patients
      had objective response, including 10 (19%) complete remissions (CRs), and 2 (3%)
      CRs with incomplete platelet recovery (CRp). Among 10 elderly patients with acute
      myelogenous leukemia or myelodysplastic syndrome, 5 (50%) had a response (4CRs,
      1CRp's). Induction mortality was observed in 1 (2%) patient. Major cytogenetic
      response was documented in 6 of 8 responders. Remission duration was 7.2 months
      (range, 1.3-12.6+ months). Overall survival was 15.3 months (range, 4.6-20.2+
      months) in responders. Transient DNA hypomethylation and global histone H3 and H4
      acetylation were induced, and were associated with p15 reactivation. Patients
      with lower pretreatment levels of p15 methylation had a significantly higher
      response rate. In summary, this combination of epigenetic therapy in leukemia was
      safe and active, and was associated with transient reversal of aberrant
      epigenetic marks.

PMID- 16882712
TI  - Rac GTPases regulate the morphology and deformability of the erythrocyte
      cytoskeleton.
AB  - Actin oligomers are a significant structural component of the erythrocyte
      cytoskeleton. Rac1 and Rac2 GTPases regulate actin structures and have multiple
      overlapping as well as distinct roles in hematopoietic cells; therefore, we
      studied their role in red blood cells (RBCs). Conditional gene targeting with a
      loxP-flanked Rac1 gene allowed Crerecombinase-induced deletion of Rac1 on a Rac2
      null genetic background. The Rac1(-/-);Rac2(-/-) mice developed microcytic anemia
      with a hemoglobin drop of about 20% and significant anisocytosis and
      poikilocytosis. Reticulocytes increased more than 2-fold. Rac1(-/-);Rac2(-/-)
      RBCs stained with rhodamine-phalloidin demonstrated F-actin meshwork gaps and
      aggregates under confocal microscopy. Transmission electron microscopy of the
      cytoskeleton demonstrated junctional aggregates and pronounced irregularity of
      the hexagonal spectrin scaffold. Ektacytometry confirmed that these cytoskeletal
      changes in Rac1(-/-);Rac2(-/-) erythrocytes were associated with significantly
      decreased cellular deformability. The composition of the cytoskeletal proteins
      was altered with an increased actin-to-spectrin ratio and increased
      phosphorylation (Ser724) of adducin, an F-actin capping protein. Actin and
      phosphorylated adducin of Rac1(-/-);Rac2(-/-) erythrocytes were more easily
      extractable by Triton X-100, indicating weaker association to the cytoskeleton.
      Thus, deficiency of Rac1 and Rac2 GTPases in mice alters actin assembly in RBCs
      and causes microcytic anemia with reticulocytosis, implicating Rac GTPases as
      dynamic regulators of the erythrocyte cytoskeleton organization.

PMID- 16882713
TI  - MicroRNAs: regulators of gene expression and cell differentiation.
AB  - The existence and roles of a class of abundant regulatory RNA molecules have
      recently come into sharp focus. Micro-RNAs (miRNAs) are small (approximately 22
      bases), non-protein-coding RNAs that recognize target sequences of imperfect
      complementarity in cognate mRNAs and either destabilize them or inhibit protein
      translation. Although mechanisms of miRNA biogenesis have been elucidated in some
      detail, there is limited appreciation of their biological functions. Reported
      examples typically focus on miRNA regulation of a single tissue-restricted
      transcript, often one encoding a transcription factor, that controls a specific
      aspect of development, cell differentiation, or physiology. However,
      computational algorithms predict up to hundreds of putative targets for
      individual miRNAs, single transcripts may be regulated by multiple miRNAs, and
      miRNAs may either eliminate target gene expression or serve to finetune
      transcript and protein levels. Theoretical considerations and early experimental
      results hence suggest diverse roles for miRNAs as a class. One appealing
      possibility, that miRNAs eliminate low-level expression of unwanted genes and
      hence refine unilineage gene expression, may be especially amenable to evaluation
      in models of hematopoiesis. This review summarizes current understanding of miRNA
      mechanisms, outlines some of the important outstanding questions, and describes
      studies that attempt to define miRNA functions in hematopoiesis.

PMID- 16882714
TI  - The Vav binding site of the non-receptor tyrosine kinase Syk at Tyr 348 is
      critical for beta2 integrin (CD11/CD18)-mediated neutrophil migration.
AB  - Leukocyte adhesion via beta(2) integrins (CD11/CD18) activates the tyrosine
      kinase Syk. We found that Syk was enriched at the lamellipodium during N-formyl
      Met-Leu-Phe-induced migration of neutrophil-like differentiated HL-60 cells.
      Here, Syk colocalized with Vav, a guanine nucleotide exchange factor for Rac and
      Cdc42. The enrichment of Syk at the lamellipodium and its colocalization with Vav
      were absent upon expression of a Syk kinase-dead mutant (Syk K402R) or a Syk
      mutant lacking the binding site of Vav (Syk Y348F). Live cell imaging revealed
      that both mutations resulted in excessive lamellipodium formation and severely
      compromised migration compared with control cells. Similar results were obtained
      upon down-regulation of Syk by RNA interference (RNAi) technique as well as in
      Syk(-/-) neutrophils from wild-type mice reconstituted with Syk(-/-) bone marrow.
      A pivotal role of Syk in vivo was demonstrated in the Arthus reaction, where
      neutrophil extravasation, edema formation, and hemorrhage were profoundly
      diminished in Syk(-/-) bone marrow chimeras compared with those in control
      animals. In the inflamed cremaster muscle, Syk(-/-) neutrophils revealed a defect
      in adhesion and migration. These findings indicate that Syk is critical for
      beta(2) integrin-mediated neutrophil migration in vitro and plays a fundamental
      role in neutrophil recruitment during the inflammatory response in vivo.

PMID- 16882715
TI  - Importance of dosage standardization for interpreting transcriptomal signature
      profiles: evidence from studies of xenoestrogens.
AB  - To obtain insights into similarities and differences in the biological actions of
      related drugs or toxic agents, their transcriptomal signature profiles (TSPs)
      have been examined in a large number of studies. However, many such reports did
      not provide proper justification for the dosage criteria of each agent. Using a
      well characterized cell culture model of estrogen-dependent proliferation of MCF7
      human breast cancer cells, we demonstrate how different approaches to dosage
      standardization exert critical influences on TSPs, leading to different and even
      conflicting conclusions. Using quantitative cellular response (QCR)-based dosage
      criteria, TSPs were determined by Affymetrix microarray when cells were
      proliferating at comparable rates in the presence of various estrogens. We
      observed that TSPs of the xenoestrogens (e.g., genistein or bisphenol A) were
      clearly different from the TSP of 17beta-estradiol; namely, the former strongly
      enhanced expression of genes involved in mitochondrial oxidative phosphorylation,
      whereas the latter showed minimal effects. In contrast, TSPs for genistein and
      17beta-estradiol were indistinguishable by using the marker gene expression-based
      dosage criteria, conditions in which there was comparable expression of the mRNA
      transcripts for the estrogen-inducible WISP2 gene. Our findings indicate that
      determination and interpretation of TSPs in pharmacogenomic and toxicogenomic
      studies that examine the transcriptomal actions of related agents by microarray
      require a clear rationale for the dosage standardization method to be used. We
      suggest that future studies involving TSP analyses use quantitative and objective
      dosage standardization methods, such as those with quantitative cellular response
      or marker gene expression-based dosage criteria.

PMID- 16882716
TI  - A genomewide screen for components of the RNAi pathway in Drosophila cultured
      cells.
AB  - Posttranscriptional silencing by RNAi is initiated by dsRNAs that are processed
      into siRNAs that ultimately target homologous mRNAs for degradation. We used
      luciferase reporter constructs and a cultured cell-based assay to perform a
      genomewide screen for components of the RNAi pathway in Drosophila melanogaster.
      The screen identified seven genes that affect the RNAi response, five with
      previously described function (AGO2, Tis11, Hsc70-3, Hsc70-4, and hdc) and two
      annotated genes (CG17265 and CG10883).

PMID- 16882717
TI  - Unique players in the BMP pathway: small C-terminal domain phosphatases
      dephosphorylate Smad1 to attenuate BMP signaling.
AB  - Smad transcription factors are key signal transducers for the TGF-beta/bone
      morphogenetic protein (BMP) family of cytokines and morphogens. C-terminal serine
      phosphorylation by TGF-beta and BMP membrane receptors drives Smads into the
      nucleus as transcriptional regulators. Dephosphorylation and recycling of
      activated Smads is an integral part of this process, which is critical for
      agonist sensing by the cell. However, the nuclear phosphatases involved have
      remained unknown. Here we provide functional, biochemical, and embryological
      evidence identifying the SCP (small C-terminal domain phosphatase) family of
      nuclear phosphatases as mediators of Smad1 dephosphorylation in the BMP signaling
      pathway in vertebrates. Xenopus SCP2/Os4 inhibits BMP activity in the presumptive
      ectoderm and leads to neuralization. In Xenopus embryos, SCP2/Os4 and human SCP1,
      2, and 3 cause selective dephosphorylation of Smad1 compared with Smad2,
      inhibiting BMP- and Smad1-dependent transcription and leading to the induction of
      the secondary dorsal axis. In human cells, RNAi-mediated depletion of SCP1 and
      SCP2 increases the extent and duration of Smad1 phosphorylation in response to
      BMP, the transcriptional action of Smad1, and the strength of endogenous BMP gene
      responses. The present identification of the SCP family as Smad C-terminal
      phosphatases sheds light on the events that attenuate Smad signaling and reveals
      unexpected links to the essential phosphatases that control RNA polymerase II in
      eukaryotes.

PMID- 16882718
TI  - Age-dependent accumulation of recombinant cells in the mouse pancreas revealed by
      in situ fluorescence imaging.
AB  - Mitotic homologous recombination (HR) is critical for the repair of double-strand
      breaks, and conditions that stimulate HR are associated with an increased risk of
      deleterious sequence rearrangements that can promote cancer. Because of the
      difficulty of assessing HR in mammals, little is known about HR activity in
      mammalian tissues or about the effects of cancer risk factors on HR in vivo. To
      study HR in vivo, we have used fluorescent yellow direct repeat mice, in which an
      HR event at a transgene yields a fluorescent phenotype. Results show that HR is
      an active pathway in the pancreas throughout life, that HR is induced in vivo by
      exposure to a cancer chemotherapeutic agent, and that recombinant cells
      accumulate with age in pancreatic tissue. Furthermore, we developed an in situ
      imaging approach that reveals an increase in both the frequency and the sizes of
      isolated recombinant cell clusters with age, indicating that both de novo
      recombination events and clonal expansion contribute to the accumulation of
      recombinant cells with age. This work demonstrates that aging and exposure to a
      cancer chemotherapeutic agent increase the frequency of recombinant cells in the
      pancreas, and it also provides a rapid method for revealing additional factors
      that modulate HR and clonal expansion in vivo.

PMID- 16882719
TI  - Structure of the nuclear exosome component Rrp6p reveals an interplay between the
      active site and the HRDC domain.
AB  - The multisubunit eukaryotic exosome is an essential RNA processing and
      degradation machine. In its nuclear form, the exosome associates with the
      auxiliary factor Rrp6p, which participates in both RNA processing and degradation
      reactions. The crystal structure of Saccharomyces cerevisiae Rrp6p displays a
      conserved RNase D core with a flanking HRDC (helicase and RNase D C-terminal)
      domain in an unusual conformation shown to be important for the processing
      function of the enzyme. Complexes with AMP and UMP, the products of the RNA
      degradation process, reveal how the protein specifically recognizes
      ribonucleotides and their bases. Finally, in vivo mutational studies show the
      importance of the domain contacts for the processing function of Rrp6p and
      highlight fundamental differences between the protein and its prokaryotic RNase D
      counterparts.

PMID- 16882721
TI  - Drosophila Rtf1 functions in histone methylation, gene expression, and Notch
      signaling.
AB  - The Rtf1 subunit of the Paf1 complex is required for proper monoubiquitination of
      histone H2B and methylation of histone H3 on lysines 4 (H3K4) and 79 in yeast
      Saccharomyces cerevisiae. Using RNAi, we examined the role of Rtf1 in histone
      methylation and gene expression in Drosophila melanogaster. We show that
      Drosophila Rtf1 (dRtf1) is required for proper gene expression and development.
      Furthermore, we show that RNAi-mediated reduction of dRtf1 results in a reduction
      in histone H3K4 trimethylation levels on bulk histones and chromosomes in vivo,
      indicating that the histone modification pathway via Rtf1 is conserved among
      yeast, Drosophila, and human. Recently, it was demonstrated that histone H3K4
      methylation mediated via the E3 ligase Bre1 is critical for transcription of
      Notch target genes in Drosophila. Here we demonstrate that the dRtf1 component of
      the Paf1 complex functions in Notch signaling.

PMID- 16882720
TI  - Reconstitution of paired T cell receptor alpha- and beta-chains from
      microdissected single cells of human inflammatory tissues.
AB  - We describe a strategy to "revive" putatively pathogenic T cells from frozen
      specimens of human inflammatory target organs. To distinguish pathogenic from
      irrelevant bystander T cells, we focused on cells that were (i) clonally expanded
      and (ii) in direct morphological contact with a target cell. Using CDR3
      spectratyping, we identified clonally expanded T cell receptor (TCR) beta-chains
      in muscle sections of patients with inflammatory muscle diseases. By
      immunohistochemistry, we identified those Vbeta-positive T cells that fulfilled
      the morphological criteria of myocytotoxicity and isolated them by laser
      microdissection. Next, we identified coexpressed pairs of TCR alpha- and beta
      chains by a multiplex PCR protocol, which allows the concomitant amplification of
      both chains from single cells. This concomitant amplification had not been
      achieved previously in histological sections, mainly because of the paucity of
      available anti-alpha-chain antibodies and the great heterogeneity of the alpha
      chain genes. From muscle tissue of a patient with polymyositis, we isolated 64 T
      cells that expressed an expanded Vbeta1 chain. In 23 of these cells, we
      identified the corresponding alpha-chain. Twenty of these 23 alpha-chains were
      identical, suggesting antigen-driven selection. After functional reconstitution
      of the alphabeta-pairs, their antigen-recognition properties could be studied.
      Our results open avenues for combined analysis of the full TCR alpha- and beta
      chain repertoire in human inflammatory tissues.

PMID- 16882722
TI  - The ATP-sensitive potassium (KATP) channel-encoded dSUR gene is required for
      Drosophila heart function and is regulated by tinman.
AB  - The homeobox transcription factor Tinman plays an important role in the
      initiation of heart development. Later functions of Tinman, including the target
      genes involved in cardiac physiology, are less well studied. We focused on the
      dSUR gene, which encodes an ATP-binding cassette transmembrane protein that is
      expressed in the heart. Mammalian SUR genes are associated with K(ATP) (ATP
      sensitive potassium) channels, which are involved in metabolic homeostasis. We
      provide experimental evidence that Tinman directly regulates dSUR expression in
      the developing heart. We identified a cis-regulatory element in the first intron
      of dSUR, which contains Tinman consensus binding sites and is sufficient for
      faithful dSUR expression in the fly's myocardium. Site-directed mutagenesis of
      this element shows that these Tinman sites are critical to dSUR expression, and
      further genetic manipulations suggest that the GATA transcription factor Pannier
      is synergistically involved in cardiac-restricted dSUR expression in vivo.
      Physiological analysis of dSUR knock-down flies supports the idea that dSUR plays
      a protective role against hypoxic stress and pacing-induced heart failure.
      Because dSUR expression dramatically decreases with age, it is likely to be a
      factor involved in the cardiac aging phenotype of Drosophila. dSUR provides a
      model for addressing how embryonic regulators of myocardial cell commitment can
      contribute to the establishment and maintenance of cardiac performance.

PMID- 16882723
TI  - A KaiC-associating SasA-RpaA two-component regulatory system as a major circadian
      timing mediator in cyanobacteria.
AB  - KaiA, KaiB, and KaiC clock proteins from cyanobacteria and ATP are sufficient to
      reconstitute the KaiC phosphorylation rhythm in vitro, whereas almost all gene
      promoters are under the control of the circadian clock. The mechanism by which
      the KaiC phosphorylation cycle drives global transcription rhythms is unknown.
      Here, we report that RpaA, a potential DNA-binding protein that acts as a cognate
      response regulator of the KaiC-interacting kinase SasA, mediates between KaiC
      phosphorylation and global transcription rhythms. Circadian transcription was
      severely attenuated in sasA (Synechococcus adaptive sensor A)- and rpaA
      (regulator of phycobilisome-associated)-mutant cells, and the phosphotransfer
      activity from SasA to RpaA changed dramatically depending on the circadian state
      of a coexisting Kai protein complex in vitro. We propose a model in which the
      SasA-RpaA two-component system mediates time signals from the enzymatic
      oscillator to drive genome-wide transcription rhythms in cyanobacteria. Moreover,
      our results indicate the presence of secondary output pathways from the clock to
      transcription control, suggesting that multiple pathways ensure a genome-wide
      circadian system.

PMID- 16882724
TI  - Structure of FliM provides insight into assembly of the switch complex in the
      bacterial flagella motor.
AB  - Bacteria switch the direction their flagella rotate to control movement. FliM,
      along with FliN and FliG, compose a complex in the motor that, upon binding
      phosphorylated CheY, reverses the sense of flagellar rotation. The 2.0-A
      resolution structure of the FliM middle domain (FliM(M)) from Thermotoga maritima
      reveals a pseudo-2-fold symmetric topology similar to the CheY phosphatases CheC
      and CheX. A variable structural element, which, in CheC, mediates binding to CheD
      (alpha2') and, in CheX, mediates dimerization (beta'(x)), has a truncated
      structure unique to FliM (alpha2'). An exposed helix of FliM(M) (alpha1) does not
      contain the catalytic residues of CheC and CheX but does include positions
      conserved in FliM sequences. Cross-linking experiments with site-directed
      cysteine mutants show that FliM self-associates through residues on alpha1 and
      alpha2'. CheY activated by BeF(3)(-) binds to FliM with approximately 40-fold
      higher affinity than CheY (K(d) = 0.04 microM vs. 2 microM). Mapping residue
      conservation, suppressor mutation sites, binding data, and deletion analysis onto
      the FliM(M) surface defines regions important for contacts with the stator
      interacting protein FliG and for either counterclockwise or clockwise rotation.
      Association of 33-35 FliM subunits would generate a 44- to 45-nm-diameter disk,
      consistent with the known dimensions of the C-ring. The localization of
      counterclockwise- and clockwise-biasing mutations to distinct surfaces suggests
      that the binding of phosphorylated CheY cooperatively realigns FliM around the
      ring.

PMID- 16882725
TI  - AMPA receptors regulate experience-dependent dendritic arbor growth in vivo.
AB  - The size and shape of neuronal dendritic arbors affect the number and type of
      synaptic inputs, as well as the complexity and function of brain circuits. In the
      intact brain, dendritic arbor growth and the development of excitatory
      glutamatergic synapse are concurrent. Consequently, it has been difficult to
      resolve whether synaptic inputs drive dendritic arbor development. Here, we test
      the role of AMPA receptor (AMPAR)-mediated glutamatergic transmission in dendrite
      growth by expressing peptides corresponding to the intracellular C-terminal
      domains of AMPAR subunits GluR1 (GluR1Ct) and GluR2 (GluR2Ct) in optic tectal
      neurons of the Xenopus retinotectal system. These peptides significantly reduce
      AMPAR synaptic transmission in transfected neurons while leaving visual system
      circuitry intact. Daily in vivo imaging over 5 days revealed that GluR1Ct or
      GluR2Ct expression dramatically impaired dendrite growth, resulting in less
      complex arbors than controls. Time-lapse images collected at 2-h intervals over 6
      h show that both GluR1Ct and GluR2Ct decrease branch lifetimes. Ultrastructural
      analysis indicates that synapses formed onto neurons expressing the GluRCt are
      less mature than synapses onto control neurons. These data suggest that the
      failure to form complex arbors is due to reduced stabilization of new synapses
      and dendritic branches. Although visual stimulation increases dendritic arbor
      growth rates in control tectal neurons, a weak postsynaptic response to visual
      experience in GluRCt-expressing cells leads to retraction of branches. These
      results indicate that AMPAR-mediated transmission underlies experience-dependent
      dendritic arbor growth by stabilizing branches, and support a competition-based
      model for dendrite growth.

PMID- 16882726
TI  - Nitric oxide activation of guanylyl cyclase in cells revisited.
AB  - Nitric oxide (NO) elicits physiological effects in cells largely by activating
      guanylyl cyclase (GC)-coupled receptors, leading to cGMP accumulation. Like other
      receptor-coupled effector mechanisms, NO stimulation of GC activity was
      previously considered to be a graded, concentration-dependent response, with
      deactivation following swiftly once the agonist disappeared. Recently, a new and
      unconventional mechanism has been proposed from experiments on purified protein
      [Cary, S. P. L., Winger, J. A. & Marletta, M. A. (2005) Proc. Natl. Acad. Sci.
      USA 102, 13064-13069]. It was concluded that GC in vivo will display a dual
      regulation by NO: a long-lasting tonic activity (10-20% of maximum) due to
      persistent occupation by NO of the heme binding site and phasic activity due to
      engagement of another unidentified, lower affinity site. The hypothesis was first
      tested by monitoring GC activity in rat platelets maintained in vitro and exposed
      to calibrated NO transients. The kinetics was as expected for a single binding
      site for NO (EC(50) = 10 nM), with activation and deactivation of enzyme activity
      conforming to the predictions of a simple receptor model. No tonic GC activity
      attributable to long-term NO binding was detected after exposure to the full
      range of active NO concentrations (peaking at 2-500 nM). Comparable results were
      obtained by using neural cells isolated from the cerebellum. After exposure to
      high NO concentrations, persistent GC activity could be recorded, but this
      activity was caused artifactually by secondary NO sources being formed in the
      medium. The new scheme for regulation of GC activity by NO is of doubtful
      relevance to cells.

PMID- 16882727
TI  - The putatively functional Mkrn1-p1 pseudogene is neither expressed nor imprinted,
      nor does it regulate its source gene in trans.
AB  - A recently promoted genome evolution model posits that mammalian pseudogenes can
      regulate their founding source genes, and it thereby ascribes an important
      function to "junk DNA." This model arose from analysis of a serendipitous mouse
      mutant in which a transgene insertion/deletion caused severe polycystic kidney
      disease and osteogenesis imperfecta with approximately 80% perinatal lethality,
      when inherited paternally [Hirotsune, S., et al. (2003) Nature 423, 91-96]. The
      authors concluded that the transgene reduced the expression of a nearby
      transcribed and imprinted pseudogene, Mkrn1-p1. This reduction in chromosome 5
      imprinted Mkrn1-p1 transcripts was proposed to destabilize the cognate chromosome
      6 Mkrn1 source gene mRNA, with a partial reduction in one Mkrn1 isoform leading
      to the imprinted phenotype. Here, we show that 5' Mkrn1-p1 is fully methylated on
      both alleles, a pattern indicative of silenced chromatin, and that Mkrn1-p1 is
      not transcribed and therefore cannot stabilize Mkrn1 transcripts in trans. A
      small, truncated, rodent-specific Mkrn1 transcript explains the product
      erroneously attributed to Mkrn1-p1. Additionally, Mkrn1 expression is not
      imprinted, and 5' Mkrn1 is fully unmethylated. Finally, mice in which Mkrn1 has
      been directly disrupted show none of the phenotypes attributed to a partial
      reduction of Mkrn1. These data contradict the previous suggestions that Mkrn1-p1
      is imprinted, and that either it or its source Mkrn1 gene relates to the original
      imprinted transgene phenotype. This study invalidates the data upon which the
      pseudogene trans-regulation model is based and therefore strongly supports the
      view that mammalian pseudogenes are evolutionary relics.

PMID- 16882728
TI  - Phonological typicality influences on-line sentence comprehension.
AB  - Since Saussure, the relationship between the sound and the meaning of words has
      been regarded as largely arbitrary. Here, however, we show that a probabilistic
      relationship exists between the sound of a word and its lexical category. Corpus
      analyses of nouns and verbs indicate that the phonological properties of the
      individual words in these two lexical categories form relatively separate and
      coherent clusters, with some nouns sounding more typical of the noun category
      than others and likewise for verbs. Additional analyses reveal that the
      phonological properties of nouns and verbs affect lexical access, and we also
      demonstrate the influence of such properties during the on-line processing of
      both simple unambiguous and syntactically ambiguous sentences. Thus, although the
      sound of a word may not provide cues to its specific meaning, phonological
      typicality, the degree to which the sound properties of an individual word are
      typical of other words in its lexical category, affects both word- and sentence
      level language processing. The findings are consistent with a perspective on
      language comprehension in which sensitivity to multiple syntactic constraints in
      adulthood emerges as a product of language-development processes that are driven
      by the integration of multiple cues to linguistic structure, including
      phonological typicality.

PMID- 16882729
TI  - Caenorhabditis elegans ortholog of a diabetes susceptibility locus: oga-1 (O
      GlcNAcase) knockout impacts O-GlcNAc cycling, metabolism, and dauer.
AB  - A dynamic cycle of O-linked N-acetylglucosamine (O-GlcNAc) addition and removal
      acts on nuclear pore proteins, transcription factors, and kinases to modulate
      cellular signaling cascades. Two highly conserved enzymes (O-GlcNAc transferase
      and O-GlcNAcase) catalyze the final steps in this nutrient-driven "hexosamine
      signaling pathway." A single nucleotide polymorphism in the human O-GlcNAcase
      gene is linked to type 2 diabetes. Here, we show that Caenorhabditis elegans oga
      1 encodes an active O-GlcNAcase. We also describe a knockout allele, oga
      1(ok1207), that is viable and fertile yet accumulates O-GlcNAc on nuclear pores
      and other cellular proteins. Interfering with O-GlcNAc cycling with either oga
      1(ok1207) or the O-GlcNAc transferase-null ogt-1(ok430) altered Ser- and Thr
      phosphoprotein profiles and increased glycogen synthase kinase 3beta (GSK-3beta)
      levels. Both the oga-1(ok1207) and ogt-1(ok430) strains showed elevated stores of
      glycogen and trehalose, and decreased lipid storage. These striking metabolic
      changes prompted us to examine the insulin-like signaling pathway controlling
      nutrient storage, longevity, and dauer formation in the C. elegans O-GlcNAc
      cycling mutants. Indeed, we found that the oga-1(ok1207) knockout augmented dauer
      formation induced by a temperature sensitive insulin-like receptor (daf-2) mutant
      under conditions in which the ogt-1(ok430)-null diminished dauer formation. Our
      findings suggest that the enzymes of O-GlcNAc cycling "fine-tune" insulin-like
      signaling in response to nutrient flux. The knockout of O-GlcNAcase (oga-1) in C.
      elegans mimics many of the metabolic and signaling changes associated with human
      insulin resistance and provides a genetically amenable model of non-insulin
      dependent diabetes.

PMID- 16882730
TI  - Crystal structure and mechanistic determinants of SARS coronavirus nonstructural
      protein 15 define an endoribonuclease family.
AB  - The approximately 30-kb coronavirus (+)RNA genome is replicated and transcribed
      by a membrane-bound replicase complex made up of 16 viral nonstructural proteins
      (nsp) with multiple enzymatic activities. The complex includes an RNA
      endonuclease, NendoU, that is conserved among nidoviruses but no other RNA virus,
      making it a genetic marker of this virus order. NendoU (nsp15) is a Mn(2+)
      dependent, uridylate-specific enzyme, which leaves 2'-3'-cyclic phosphates 5' to
      the cleaved bond. Neither biochemical nor sequence homology criteria allow a
      classification of nsp15 into existing endonuclease families. Here, we report the
      crystal structure of the severe acute respiratory syndrome coronavirus nsp15 at
      2.6-A resolution. Nsp15 exhibits a unique fold and assembles into a toric hexamer
      with six potentially active, peripheric catalytic sites. The structure and the
      spatial arrangement of the catalytic residues into an RNase A-like active site
      define a separate endonuclease family, endoU, and represent another spectacular
      example of convergent evolution toward an enzymatic function that is critically
      involved in the coronavirus replication cycle.

PMID- 16882732
TI  - Nuclear targeting of Akt antagonizes aspects of cardiomyocyte hypertrophy.
AB  - The serine/threonine kinase Akt regulates cellular survival, proliferation, gene
      transcription, protein translation, metabolism, and differentiation. Although Akt
      substrates are found throughout the cell, activated Akt normally accumulates in
      the nucleus, suggesting that biologically relevant targets are located there.
      Consequences of nuclear Akt signaling in cardiomyocytes were explored by using
      nuclear-targeted Akt (Akt-nuc). Accumulation of Akt-nuc did not provoke
      hypertrophy, unlike constitutively activated Akt. Instead, Akt-nuc inhibited
      hypertrophy concurrent with increased atrial natriuretic peptide (ANP) expression
      that depended upon phosphatidylinositol-3 kinase activity. Akt-nuc
      antihypertrophic effects were blocked by inhibition of either guanylyl cyclase A
      receptor or cyclic guanosine monophosphate-dependent protein kinase in cultured
      cardiomyocytes. Corroborating evidence showed blunted acute hypertrophic
      remodeling in Akt-nuc transgenic mice after transverse aortic constriction
      coincident with higher ANP expression and smaller myocyte volume. In addition,
      Akt-nuc expression improved systolic function and survival in the chronic phase
      of transverse aortic constriction-induced hypertrophy. Thus, Akt-nuc antagonizes
      certain aspects of hypertrophy through autocrine/paracrine stimulation of a
      phosphatidylinositol-3 kinase-dependent signaling cascade that promotes ANP
      expression, resulting in a unique combination of prosurvival coupled with
      antihypertrophic signaling.

PMID- 16882731
TI  - Rabs and their effectors: achieving specificity in membrane traffic.
AB  - Rab proteins constitute the largest branch of the Ras GTPase superfamily. Rabs
      use the guanine nucleotide-dependent switch mechanism common to the superfamily
      to regulate each of the four major steps in membrane traffic: vesicle budding,
      vesicle delivery, vesicle tethering, and fusion of the vesicle membrane with that
      of the target compartment. These different tasks are carried out by a diverse
      collection of effector molecules that bind to specific Rabs in their GTP-bound
      state. Recent advances have not only greatly extended the number of known Rab
      effectors, but have also begun to define the mechanisms underlying their distinct
      functions. By binding to the guanine nucleotide exchange proteins that activate
      the Rabs certain effectors act to establish positive feedback loops that help to
      define and maintain tightly localized domains of activated Rab proteins, which
      then serve to recruit other effector molecules. Additionally, Rab cascades and
      Rab conversions appear to confer directionality to membrane traffic and couple
      each stage of traffic with the next along the pathway.

PMID- 16882733
TI  - Molecular and genomic characterisation of cryptic chromosomal alterations leading
      to paternal duplication of the 11p15.5 Beckwith-Wiedemann region.
AB  - BACKGROUND: Beckwith-Wiedemann syndrome (BWS) is an overgrowth disorder with
      increased risk of paediatric tumours. The aetiology involves epigenetic and
      genetic alterations affecting the 11p15 region, methylation of the differentially
      methylated DMR2 region being the most common defect, while less frequent
      aetiologies include mosaic paternal 11p uniparental disomy (11patUPD), maternally
      inherited mutations of the CDKN1C gene, and hypermethylation of DMR1. A few
      patients have cytogenetic abnormalities involving 11p15.5. METHODS: Screening of
      70 trios of BWS probands for 11p mosaic paternal UPD and for cryptic cytogenetic
      rearrangements using microsatellite segregation analysis identified a profile
      compatible with paternal 11p15 duplication in two patients. RESULTS: Fluorescence
      in situ hybridisation analysis revealed in one case the unbalanced translocation
      der(21)t(11;21)(p15.4;q22.3) originated from missegregation of a cryptic paternal
      balanced translocation. The second patient, trisomic for D11S1318, carried a
      small de novo dup(11)(p15.5p15.5), resulting from unequal recombination at
      paternal meiosis I. The duplicated region involves only IC1 and spares IC2/LIT1,
      as shown by fluorescent in situ hybridisation (FISH) mapping of the proximal
      duplication breakpoint within the amino-terminal part of KvLQT1. CONCLUSIONS: An
      additional patient with Wolf-Hirschorn syndrome was shown by FISH studies to
      carry a der(4)t(4;11)(p16.3;p15.4), contributed by a balanced translocation
      father. Interestingly, refined breakpoint mapping on 11p and the critical regions
      on the partner 21q and 4p chromosomal regions suggested that both translocations
      affecting 11p15.4 are mediated by segmental duplications. These findings of
      chromosomal rearrangements affecting 11p15.5-15.4 provide a tool to further
      dissect the genomics of the BWS region and the pathogenesis of this imprinting
      disorder.

PMID- 16882734
TI  - Genetic predictors for acute experimental cold and heat pain sensitivity in
      humans.
AB  - BACKGROUND: The genetic contribution to pain sensitivity underlies a complex
      composite of parallel pain pathways, multiple mechanisms, and diverse inter
      individual pain experiences and expectations. METHODS: Variations for genes
      encoding receptors related to cold and heat sensation, such as transient receptor
      potential A subtype 1 (TRPA1), M subtype 8 (TRPM8), V subtype 1 (TRPV1), delta
      opioid receptor subtype 1 (OPRD1), catechol O-methyltransferase (COMT), and fatty
      acid amide hydrolyase (FAAH), were investigated in four major ethnic populations.
      RESULTS: We defined 13 haplotype blocks in European Americans, seven blocks in
      African Americans, seven blocks in Hispanic subjects, and 11 blocks in Asian
      Americans. Further study in European American subjects found significant
      associations between short duration cold pain sensitivity and variations in
      TRPA1, COMT, and FAAH in a gender dependent manner. Our observations demonstrate
      that genetic variations in TRPA1, COMT, and FAAH contribute gender specifically
      to individual variations in short duration cold pain sensitivity in a European
      American cohort. CONCLUSIONS: The effects of TRPA1 variations on experimental
      short duration heat pain sensitivity may contribute to inter-individual variation
      in pain sensitivity in humans.

PMID- 16882735
TI  - STK11 status and intussusception risk in Peutz-Jeghers syndrome.
AB  - BACKGROUND: Peutz-Jeghers syndrome (PJS) is caused by germline STK11 mutations
      and characterised by gastrointestinal polyposis. Although small bowel
      intussusception is a recognised complication of PJS, risk varies between
      patients. OBJECTIVE: To analyse the time to onset of intussusception in a large
      series of PJS probands. METHODS: STK11 mutation status was evaluated in 225 PJS
      probands and medical histories of the patients reviewed. RESULTS: 135 (60%) of
      the probands possessed a germline STK11 mutation; 109 (48%) probands had a
      history of intussusception at a median age of 15.0 years but with wide
      variability (range 3.7 to 45.4 years). Median time to onset of intussusception
      was not significantly different between those with identified mutations and those
      with no mutation detected, at 14.7 years and 16.4 years, respectively (log-rank
      test of difference, chi(2) = 0.58, with 1df; p = 0.45). Similarly no differences
      were observed between patient groups on the basis of the type or site of STK11
      mutation. CONCLUSIONS: The risk of intussusception in PJS is not influenced by
      STK11 mutation status.

PMID- 16882736
TI  - CYP19 haplotypes increase risk for Alzheimer's disease.
AB  - Cytochrome P450 aromatase, an enzyme that catalyses the conversion of androgens
      to oestrogen, is expressed at high levels in the gonads and in the brain.
      Aromatase activity is increased in the nucleus basalis of Meynert during aging
      and in Alzheimer's disease (AD), making the gene (CYP19), at 15q21.1, a potential
      candidate risk factor. We examined 18 single nucleotide polymorphisms spanning
      the 5'-untranslated region and the entire coding region of CYP19 in 227 patients
      with AD and 131 control spouses. We found that the gene region could be divided
      into two haplotype blocks; a haplotype in block 1 and a haplotype in block 2
      increased the risk of developing the disease by twofold in APOE 4 carriers. The
      implication of two haplotypes conferring increased risk for AD warrants further
      investigation of the regulation of aromatase activity in brain.

PMID- 16882738
TI  - Reply to Dr Raux et al.: Molecular diagnosis of autosomal dominant early onset
      Alzheimer's disease: an update (J Med Genet 2005;42:793-5).

PMID- 16882737
TI  - Association of lung function decline with the heme oxygenase-1 gene promoter
      microsatellite polymorphism in a general population sample. Results from the
      European Community Respiratory Health Survey (ECRHS), France.
AB  - Inducible heme oxygenase (HO-1) acts against oxidants that are thought to play a
      major role in the pathogenesis of chronic obstructive pulmonary disease (COPD),
      characterised by impaired lung function. A (GT)(n) repeat polymorphism in the HO
      1 gene promoter can modulate the gene transcription in response to oxidative
      stress. We hypothesised that this polymorphism could be associated with the level
      of lung function and decline in subjects exposed to oxidative aggression
      (smokers). We genotyped 749 French subjects (20-44 years, 50% men, 40% never
      smokers) examined in both 1992 and 2000 as part of the ECRHS. Lung function was
      assessed by forced expiratory volume in 1 second (FEV1) and FEV1/forced
      ventilatory capacity (FVC) ratio. We compared long (L) allele carriers ((GT)(n) >
      or =33 repeats for one or two alleles) to non-carriers. Cross sectionally, in
      2000, L allele carriers showed lower FEV1/FVC than non-carriers. During the 8
      year period, the mean annual FEV1 and FEV1/FVC declines were -30.9 (31.1) ml/year
      and -1.8 (6.1) U/year, respectively. FEV1/FVC decline was steeper in L allele
      carriers than in non-carriers (-2.6 (5.5) v -1.5 (6.4), p = 0.07). There was a
      strong interaction between the L allele and smoking. In 2000, the L allele was
      associated with lower FEV(1) and FEV(1)/FVC in heavy smokers (> or =20
      cigarettes/day) only (p for interaction = 0.07 and 0.002 respectively). Baseline
      heavy smokers carrying the L allele showed the steepest FEV1 decline (-62.0 (29.5
      ml/year) and the steepest FEV1/FVC decline (-8.8 (5.4 U/year) (p for interaction
      = 0.009 and 0.0006). These results suggest that a long (L) HO-1 gene promoter in
      heavy smokers is associated with susceptibility to develop airway obstruction.

PMID- 16882739
TI  - Somatic mutations in cardiac malformations.

PMID- 16882740
TI  - Redefining the risks of prenatally ascertained supernumerary marker chromosomes:
      a collaborative study.
AB  - BACKGROUND: A marker chromosome is defined as a structurally abnormal chromosome
      that cannot be identified by routine cytogenetics. The risk for phenotypic
      abnormalities associated with a marker chromosome depends on several factors,
      including inheritance, mode of ascertainment, chromosomal origin, and the
      morphology, content, and structure of the marker. METHODS: to understand the
      karyotype-phenotype relationship of prenatally ascertained supernumerary de novo
      marker chromosomes, we combined data from prenatal cases obtained from 12
      laboratories with those from studies in the literature. We were able to obtain
      cytogenetic and phenotypic data from 108 prenatally ascertained supernumerary de
      novo marker chromosomes to refine the phenotypic risk associated with these
      markers. Because of the growing number of cases and because more techniques are
      available to delineate marker morphology, we have been able to group risk
      estimates into subcategories, such as by marker type and whether there are
      ultrasound abnormalities. RESULTS: If a de novo supernumerary marker chromosome
      is found prenatally, our data suggest there is a 26% risk for phenotypic
      abnormality when there is no other information defining the marker (such as
      chromosomal origin or information about the existing phenotype). However, if high
      resolution ultrasound studies are normal, this risk reduces to 18%. CONCLUSIONS:
      Our findings strongly support the value of additional genetic studies for more
      precisely defining the risk in individual cases involving marker chromosomes.

PMID- 16882741
TI  - Biochemical screening of type I collagen in osteogenesis imperfecta: detection of
      glycine substitutions in the amino end of the alpha chains requires
      supplementation by molecular analysis.
AB  - BACKGROUND: The biochemical test for osteogenesis imperfecta (OI) detects
      structural abnormalities in the helical region of type I collagen as delayed
      electrophoretic migration of alpha chains on SDS-urea-PAGE. Sensitivity of this
      test is based on overmodification of alpha chains in helices with a glycine
      substitution or other structural defect. The limits of detectability have not
      been reported. METHODS: We compared the collagen electrophoretic migration of 30
      probands (types III or IV OI) with known mutations in the amino half of the
      alpha1(I) and alpha2(I) chains. Differences in sensitivity were examined by 5%
      and 6% SDS-urea-PAGE, and with respect to alpha chain, location along the chain,
      and substituting amino acid. RESULTS: Sensitivity was enhanced on 5% gels, and by
      examination of intracellular and secreted collagen. In alpha1(I), substitutions
      in the first 100 residues were not detectable; 7% of cases in the current
      Mutation Consortium database are in this region. alpha1(I) substitutions between
      residues 100 and 230 were variably detectable, while those after residue 232 were
      all detected. In alpha2(I), variability of electrophoretic detection extended
      through residue 436. About a third of cases in the Consortium database are
      located in the combined variable detection region. Biochemical sensitivity did
      not correlate with substituting residue. CONCLUSIONS: Complete testing of
      probands with normal type I collagen biochemical results requires supplementation
      by molecular analysis of cDNA or gDNA in the amino third of alpha1(I) and amino
      half of alpha2(I). Mutation detection in OI is important for counselling,
      reproductive decisions, exclusion of child abuse, and genotype-phenotype
      correlations.

PMID- 16882742
TI  - The Knudson's two-hit model and timing of somatic mutation may account for the
      phenotypic diversity of focal congenital hyperinsulinism.
AB  - BACKGROUND: Congenital hyperinsulinism (CHI) is associated with focal hyperplasia
      of endocrine tissue in 40-65% of patients. Focal CHI is sporadic and is caused by
      a germline, paternally inherited, mutation of the SUR1 (ABCC8) or KIR6.2 (KCNJ11)
      genes (encoding subunits of the pancreatic ATP-dependent potassium channel)
      together with somatic maternal haploinsufficiency for 11p15.5. Plurifocal or
      large forms of focal CHI are a cause of apparent failure of surgery, and their
      underlying mechanism has not been thoroughly investigated. PATIENTS: We here
      report two patients with bifocal CHI as evidenced by relapsing hypoglycemia after
      removal of the first focal lesion and the detection of a second, distinct, focal
      adenomatous hyperplasia during later surgery (patients 1 and 2) and a patient
      with a giant focal lesion involving the major part of the pancreas (patient 3).
      RESULTS: In the three patients, a germline, paternally inherited, mutation of
      SUR1 was found. In patients 1 and 2, haploinsufficiency for the maternal 11p15.5
      region resulted from a somatic deletion specific for each of the focal lesions,
      as shown by the diversity of deletion break points. In patient 3, an identical
      somatic maternal 11p15 deletion demonstrated by similar break points was shown in
      two independent lesion samples, suggesting a very early event during pancreas
      embryogenesis. CONCLUSION: Individual patients with focal hyperinsulinism may
      have more than one focal pancreatic lesion due to separate somatic maternal
      deletion of the 11p15 region. These patients and those with solitary focal
      lesions may follow the two-hit model described by Knudson. The stage of
      embryogenesis at which the somatic event occurs may account for the observed
      histological diversity (early event giant lesion, later event small lesion).

PMID- 16882743
TI  - Decreased total and high molecular weight adiponectin are independent risk
      factors for the development of type 2 diabetes in Japanese-Americans.
AB  - CONTEXT: Adiponectin is a hormone secreted by adipocytes that acts as an
      antidiabetic adipokine. Adiponectin exists as multimers in plasma, and high
      molecular weight (HMW) adiponectin is particularly thought to be the active form
      of the protein. OBJECTIVE: The aim of the study was to assess whether decreased
      total and HMW adiponectin are independent risk factors for the development of
      type 2 diabetes. DESIGN: Study subjects were Japanese-Americans enrolled in the
      Hawaii-Los Angeles-Hiroshima study between 1992 and 2002. Duration of follow-up
      was an average of 5.4 yr. PARTICIPANTS: We investigated 321 men and 445 women who
      were nondiabetic Japanese-Americans. Glucose tolerance was evaluated according to
      1997 American Diabetes Association criteria, and 112 subjects developed type 2
      diabetes during the follow-up period. MAIN OUTCOME MEASURE: The influence of
      baseline total and HMW adiponectin on the development of type 2 diabetes was the
      main outcome measure. RESULTS: Subjects who developed type 2 diabetes had
      significantly decreased plasma total and HMW adiponectin compared with those who
      did not develop the disease (P < 0.001, respectively). In a Cox proportional
      hazards model, both decreased total and HMW adiponectin levels were independent
      risk factors for the progression to type 2 diabetes after adjusting for sex, age,
      body mass index, waist-to-hip ratio, homeostasis model assessment, and
      classification of 75-g glucose tolerance test (hazards ratio: total, 0.600, P =
      0.018; HMW, 0.614, P = 0.001, respectively). Dividing tertiles of adiponectin,
      hazards ratios in the lowest vs. highest tertile were total, 1.787 (95%
      confidence interval, 1.006-3.173); and HMW, 2.493 (95% confidence interval, 1.342
      4.632), after similar adjustments. CONCLUSIONS: Decreased total adiponectin is an
      independent risk factor for the progression to type 2 diabetes in Japanese
      Americans. Moreover, HMW adiponectin more closely associates with the progression
      to type 2 diabetes when compared with total adiponectin.

PMID- 16882744
TI  - Long-term mortality and incidence of renal dialysis and transplantation in type 1
      diabetes mellitus.
AB  - AIMS: We investigated long-term mortality and requirement of renal replacement
      therapy (RRT) in type 1 diabetes mellitus (T1DM) to study risk factors and late
      complication incidence of T1DM in a prospective cohort study at Lainz Hospital,
      Vienna, Austria. METHODS: In 1983-1984, T1DM patients [n = 648; 47% females, 53%
      males; age, 30 +/- 11 yr; T1DM duration, 15 +/- 9 yr; body mass index, 24 +/- 4
      kg/m(2); glycated hemoglobin (HbA1c), 7.6 +/- 1.6%] were stratified into HbA1c
      quartiles [1st, 5.9 +/- 0.5% (range, 4.2-6.5%); 2nd, 6.9 +/- 0.3% (6.6-7.4%);
      3rd, 7.9 +/- 0.3% (7.5-8.4%); and 4th, 9.6 +/- 1.3% (8.5-14.8%)]. Twenty years
      later, both endpoints (death and RRT) were investigated by record linkage with
      national registries. RESULTS: At baseline, creatinine clearance, blood pressure,
      and body mass index were comparable among the HbA1c quartiles, whereas
      albuminuria was more frequent in the 4th quartile (+15%; P < 0.03). After the 20
      yr follow-up, 13.0% of the patients had died [rate, 708 per 100,000 person-years
      (95% confidence interval, 557-859)], and 5.6% had received RRT [311 per 100,000
      person-years (95% confidence interval, 210-412)]. Patients with the highest HbA1c
      values (4th quartile) had a higher mortality rate and a greater incidence of RRT
      (P < 0.04). In the Cox proportional hazards analysis, age, male gender, increased
      HbA1c, albuminuria, and reduced creatinine clearance were predictors of mortality
      (P < 0.05). Predictors of RRT were albuminuria (P < 0.001), reduced creatinine
      clearance (P < 0.001), and belonging to the 4th HbA1c quartile (P = 0.06). In
      Kaplan-Meier analysis, mortality was linearly associated with poor glycemia,
      whereas RRT incidence appeared to rise at a HbA1c threshold of approximately
      8.5%. CONCLUSION/INTERPRETATION: In the Lainz T1DM cohort, 13.0% mortality and
      5.6% RRT were directly associated with and more frequently found in poor
      glycemia, showing that good glycemic control is essential for the longevity and
      quality of life in T1DM.

PMID- 16882745
TI  - Persistent intraprostatic androgen concentrations after medical castration in
      healthy men.
AB  - CONTEXT: The impact of serum androgen manipulation on prostate tissue hormone
      levels in normal men is unknown. Studies of men with prostate cancer have
      suggested that prostatic androgens are preserved in the setting of castration.
      Tissue androgens might stimulate prostate growth, producing adverse clinical
      consequences. OBJECTIVE: The objective of the study was to determine the effect
      of serum androgen manipulation on intraprostatic androgens in normal men. DESIGN:
      Thirteen male volunteers ages 35-55 yr (prostate-specific antigen < 2.0 ng/ml;
      normal transrectal ultrasound) were randomly assigned to: 1) a long-acting GnRH
      antagonist, acyline, every 2 wk; 2) acyline plus testosterone (T) gel (10 mg/d);
      or 3) placebo for 28 d. Serum hormones were assessed weekly. Prostate biopsies
      were obtained on d 28. Extracted androgens were measured by RIA, and
      immunohistochemistry for androgen-regulated proteins was performed. RESULTS: The
      mean decrease in serum T was 94%, whereas prostatic T and dihydrotestosterone
      levels were 70 and 80% lower, respectively, in subjects receiving acyline alone
      compared with controls (P < 0.05). Despite this decrease in prostate androgens,
      there were no detectable differences in prostate epithelial proliferation,
      apoptosis, prostate-specific antigen, and androgen receptor expression.
      CONCLUSION: In this small study of healthy subjects, despite a 94% decrease in
      serum T with medical castration, intraprostatic T and dihydrotestosterone levels
      remained 20-30% of control values, and prostate cell proliferation, apoptosis,
      and androgen-regulated protein expression were unaffected. Our data highlight the
      importance of assessing tissue hormone levels. The source of persistent prostate
      androgens associated with medical castration and their potential role in
      supporting prostate metabolism deserves further study.

PMID- 16882747
TI  - A novel missense mutation in human TTF-2 (FKHL15) gene associated with congenital
      hypothyroidism but not athyreosis.
AB  - BACKGROUND: Thyroid dysgenesis is the most frequent cause of congenital
      hypothyroidism (CH), and its genetic basis is largely unknown. Hitherto, two
      mutations in the human thyroid transcription factor 2 (TTF-2) gene have been
      described in unrelated cases of CH with cleft palate, spiky hair, variable
      choanal atresia, and complete thyroid agenesis. Here, we describe a novel TTF-2
      mutation in a female child resulting in syndromic CH in the absence of thyroid
      agenesis. RESULTS: The index case is homozygous for an arginine to cysteine
      mutation (R102C) of a highly conserved residue within the forkhead, DNA binding
      domain of TTF-2. Her consanguineous, heterozygous parents are unaffected, and the
      mutation was not detected in 100 control chromosomes. Consonant with its
      location, the R102C mutant TTF-2 protein showed loss of DNA binding and was
      transcriptionally inactive. CH in the proposita was associated with cleft palate,
      spiky hair, and bilateral choanal atresia. However, radiological studies showed
      the presence of thyroid tissue in a eutopic location. CONCLUSION: Our findings
      indicate that human thyroid development can occur despite loss of TTF-2 function
      and suggest that TTF-2 gene defects should also be considered in cases of
      syndromic CH without total athyreosis.

PMID- 16882746
TI  - Hypothalamic pituitary adrenal function during critical illness: limitations of
      current assessment methods.
AB  - CONTEXT: Activation of the hypothalamic-pituitary-adrenal (HPA) axis represents
      one of several important responses to stressful events and critical illnesses.
      Despite a large volume of published data, several controversies continue to be
      debated, such as the definition of normal adrenal response, the concept of
      relative adrenal insufficiency, and the use of glucocorticoids in the setting of
      critical illness. OBJECTIVES: The primary objective was to review some of the
      modulating factors and limitations of currently used methods of assessing HPA
      function during critical illness and provide alternative approaches in that
      setting. DESIGN: This was a critical review of relevant data from the literature
      with inclusion of previously published as well as unpublished observations by the
      author. Data on HPA function during three different forms of critical illnesses
      were reviewed: experimental endotoxemia in healthy volunteers, the response to
      major surgical procedures in patients with normal HPA, and the spontaneous acute
      to subacute critical illnesses observed in patients treated in intensive care
      units. SETTING: The study was conducted at an academic medical center.
      PATIENTS/PARTICIPANTS: Participants were critically ill subjects. INTERVENTION:
      There was no intervention. MAIN OUTCOME MEASURE: The main measure was to provide
      data on the superiority of measuring serum free cortisol during critical illness
      as contrasted to those of total cortisol measurements. RESULTS: Serum free
      cortisol measurement is the most reliable method to assess adrenal function in
      critically ill, hypoproteinemic patients. A random serum free cortisol is
      expected to be 1.8 microg/dl or more in most critically ill patients,
      irrespective of their serum binding proteins. Because the free cortisol assay is
      not currently available for routine clinical use, alternative approaches to
      estimate serum free cortisol can be used. These include calculated free cortisol
      (Coolens' method) and determining the free cortisol index (ratio of serum
      cortisol to transcortin concentrations). Preliminary data suggest that salivary
      cortisol measurements might be another alternative approach to estimating the
      free cortisol in the circulation. When serum binding proteins (albumin,
      transcortin) are near normal, measurements of total serum cortisol continue to
      provide reliable assessment of adrenal function in critically ill patients, in
      whom a random serum total cortisol would be expected to be 15 microg/dl or more
      in most patients. In hypoproteinemic critically ill subjects, a random serum
      total cortisol level is expected to be 9.5 microg/dl or more in most patients.
      Data on Cosyntropin-stimulated serum total and free cortisol levels should be
      interpreted with the understanding that the responses in critically ill subjects
      are higher than those of healthy ambulatory volunteers. The Cosyntropin-induced
      increment in serum total cortisol should not be used as a criterion for defining
      adrenal function, especially in critically ill patients. CONCLUSIONS: The routine
      use of glucocorticoids during critical illness is not justified except in
      patients in whom adrenal insufficiency was properly diagnosed or others who are
      hypotensive, septic, and unresponsive to standard therapy. When glucocorticoids
      are used, hydrocortisone should be the drug of choice and should be given at the
      lowest dose and for the shortest duration possible. The hydrocortisone dose (50
      mg every 6 h) that is mistakenly labeled as low-dose hydrocortisone leads to
      excessive elevation in serum cortisol to values severalfold greater than those
      achieved in patients with documented normal adrenal function. The latter data
      should call into question the current practice of using such doses of
      hydrocortisone even in the adrenally insufficient subjects.

PMID- 16882748
TI  - Predictors of postabsorptive ghrelin secretion after intake of different
      macronutrients.
AB  - CONTEXT: Release of ghrelin, a gastrointestinal hormone regulating feeding and
      energy balance, is blunted in obesity, a condition associated with insulin
      resistance. OBJECTIVE: The objective was to identify anthropometric and metabolic
      predictors of postabsorptive ghrelin secretion. DESIGN: We evaluated ghrelin,
      insulin, glucose, and leptin secretion overnight and after intake of different
      macronutrients. SUBJECTS: Ten obese subjects (age, 31.8 +/- 2.5 yr; body mass
      index, 43.4 +/- 0.8 kg/m(2)) and six lean subjects (age, 33.5 +/- 2.4 yr; body
      mass index, 21.8 +/- 1.4 kg/m(2)) participated in the study. MAIN OUTCOME
      MEASURES: The main outcome measures were resting energy expenditure (REE); fat
      mass; nighttime approximate entropy (ApEn) and synchronicity (cross-ApEn) of
      ghrelin, insulin, and leptin; insulin sensitivity by homeostatic model approach
      insulin-sensitivity (HOMA-S%); postabsorptive area under the curve (AUC); and
      Delta of ghrelin, insulin, glucose, and leptin after carbohydrate-, lipid-, and
      protein-rich test meals. RESULTS: Nighttime ApEn scores were higher in obese than
      lean subjects (P < 0.01). Cross-ApEn revealed a synchronicity between ghrelin
      insulin, ghrelin-leptin, and insulin-leptin in both groups. Compared with
      baseline, ghrelin decreased significantly (P < 0.01) in lean and obese subjects
      after carbohydrates (42.2 vs. 28.5%; P < 0.05), lipids (40.2 vs. 26.2%; P <
      0.01), and proteins (42.2 vs. 26.3%; P < 0.01) devoid of between-meal ghrelin
      differences. Significant associations occurred between nocturnal ghrelin ApEn and
      insulin (r = 0.53; P < 0.05), postmeal ghrelin AUCs and REE (r = -0.57; P <
      0.05), and HOMA-S% (r = 0.52; P < 0.05), postmeal ghrelin Delta and HOMA-S% (r =
      0.60; P < 0.05). REE (beta = -0.57; P = 0.02) and ghrelin ApEn (beta = -0.62; P =
      0.01) were predictors of postmeal ghrelin AUC and Delta, respectively.
      CONCLUSIONS: Obesity determined a decreased orderliness of ghrelin secretion and
      a relative loss of ghrelin-insulin synchrony. Postabsorptive ghrelin secretion
      decreased significantly both in obese and lean subjects, was related to insulin
      sensitivity, and was predicted by energy expenditure and hormone pulsatility.

PMID- 16882749
TI  - Comparison of methods to measure low serum estradiol levels in postmenopausal
      women.
AB  - CONTEXT: Accurate measurement of low serum estradiol (E(2) < 30 pg/ml or < 110
      pmol/liter) is needed to study relationships between endogenous E(2) and risks of
      diseases in older women. OBJECTIVE: The objective of this study was to determine
      whether an extraction-based (indirect) assay or a non-extraction-based (direct)
      assay correlates better with mass spectrometry and body mass index (BMI).
      DESIGN/SETTING: In a pilot study of 40 postmenopausal women, endogenous E(2)
      measurements from three indirect and four direct assay methods and gas
      chromatography-tandem mass spectrometry (GC-MS/MS) were compared. A confirmatory
      study compared an indirect and a direct assay, selected among those in the pilot
      study, to GC-MS/MS; this study was conducted in 374 postmenopausal women not
      taking hormone therapy from the Ultra Low-dose TRansdermal estrogen Assessment
      (ULTRA) trial. MAIN OUTCOMES: Pearson correlation coefficients among E(2)
      measurements by assay methods and BMI, and their confidence intervals, by bias
      corrected bootstrap method, were used. RESULTS: In the pilot study, E(2) by three
      indirect assays correlated better (P < 0.03) with GC-MS/MS and with BMI than
      measurements by four direct assays. In the confirmatory study, the indirect assay
      correlated better (P < 0.01) with GC-MS/MS and BMI than the direct assay.
      Measurements by the indirect and direct assays were overestimated, but deviations
      in direct assay measurements were less precise. Mean E(2) by the indirect and
      direct assays were higher (by 14 and 68%, respectively) and less reproducible
      than by GC-MS/MS. CONCLUSION: Until mass spectrometry is practical for wide use,
      extraction-based indirect assays may be preferable for measuring low
      postmenopausal serum E(2).

PMID- 16882750
TI  - Polycystic ovarian morphology in normal women does not predict the development of
      polycystic ovary syndrome.
AB  - CONTEXT: Polycystic ovarian morphology (PCOM) is present in 25% of normal women
      in the absence of polycystic ovary syndrome (PCOS); however, the natural history
      of PCOM is unknown. OBJECTIVE: We hypothesized that the presence of PCOM
      predisposes the development of PCOS. DESIGN: The study was a longitudinal follow
      up study over 8.2 +/- 5.2 yr (mean +/- sd; range 1.7-17.5 yr). SETTING: The study
      took place in an outpatient setting. SUBJECTS: Women who took part in a previous
      study as a normal control and had an ultrasound examination (n = 40)
      participated. INTERVENTION: Subjects underwent an interval menstrual history,
      physical exam, blood sampling, and repeat ultrasound in the follicular phase.
      MAIN OUTCOME MEASURE: Development of PCOS was diagnosed by irregular menses and
      hyperandrogenism, in the absence of other disorders. Changes in ovarian
      morphology over time were evaluated. RESULTS: At the baseline visit, 23 women
      (57.5%) had PCOM and 17 (42.5%) had normal ovarian morphology. One subject with
      PCOM developed irregular menses and presumptive PCOS. Eleven subjects with PCOM
      no longer met the criteria for PCOM at follow-up. There was no factor that
      predicted the change to normal ovarian morphology at the follow-up visit.
      CONCLUSIONS: These data suggest that PCOM in women with regular ovulatory cycles
      does not commonly predispose the development of PCOS. Although it is unusual to
      develop PCOM if the ovaries are normal on first assessment, ovaries in women with
      PCOM no longer meet the criteria for PCOM in approximately half of cases over
      time.

PMID- 16882751
TI  - Predictive value of circulating insulin-like growth factor I levels in ischemic
      stroke outcome.
AB  - CONTEXT: Cerebrovascular disease is highly prevalent in the general population,
      frequently leading to permanent invalidity and reduced quality of life. IGF-I is
      recognized as an important neuroprotective factor against cerebral hypoxic
      insult. OBJECTIVE: The objective of the study was to evaluate pituitary function,
      in particular GH-IGF-I axis, in adult patients receiving rehabilitation after an
      ischemic stroke. SUBJECTS AND METHODS: We studied 42 patients (12 females; age
      range, 50-88 yr) during rehabilitation after stroke, evaluating the relationship
      between the GH-IGF-I axis and the severity (National Institutes of Health stroke
      scale) and outcome [Rancho Los Amigos Scale of Cognitive Functioning (LCFS);
      Functional Independence Measure (FIM); modified Ranking Scale] from stroke.
      RESULTS: GH deficiency was demonstrated in five patients (11.9%). Peak GH after
      GHRH + arginine test and IGF-I levels did not correlate with severity of stroke.
      IGF-I was positively correlated with LCFS (r = 0.305, P < 0.05) and the
      difference between FIM on admission and at discharge from rehabilitation
      (DeltaFIM; r = 0.361, P < 0.02). Outcome indexes (LCFS, FIM at discharge,
      DeltaFIM) and occurrence of favorable outcome (modified Ranking Scale 0-1) were
      significantly (P < 0.05) higher in patients with IGF-I levels 161.8 mug/dl or
      greater (50th percentile of the patient distribution). LH-FSH deficiency (three
      cases), ACTH deficiency (one case), and hyperprolactinemia (two cases) were
      detected. One patient had primary hypogonadism, and six males had low
      testosterone with normal LH and FSH levels. By multivariate analysis, IGF-I level
      was the main significant predictor of DeltaFIM and LCFS. CONCLUSIONS: Ischemic
      stroke may be associated with pituitary dysfunction, particularly GH and
      gonadotropin deficiencies. The higher IGF-I levels observed in patients with
      better outcome suggest a possible neuroprotective role of IGF-I. Circulating IGF
      I may predict functional performance during rehabilitation and ischemic stroke
      outcome.

PMID- 16882752
TI  - Letrozole reduces estrogen and gonadotropin exposure in women with breast cancer
      undergoing ovarian stimulation before chemotherapy.
AB  - CONTEXT: Women with breast cancer are not typically offered embryo or oocyte
      cryopreservation to preserve their fertility before chemotherapy because of the
      potential risks associated with high estrogen levels arising from ovarian
      stimulation. OBJECTIVE: We aimed to determine whether the combination of an
      aromatase inhibitor with gonadotropin treatment in breast cancer patients
      produces comparable results to standard in vitro fertilization (IVF), without a
      significant increase in estradiol levels and delay in the initiation of
      chemotherapy. PATIENTS AND METHODS: Stages I-IIIA breast cancer patients (n = 47)
      received 5 mg/d letrozole and 150-300 IU FSH to cryopreserve embryos or oocytes.
      Age-matched retrospective controls (n = 56) were selected from women who
      underwent IVF for tubal disease. RESULTS: Whereas letrozole and FSH stimulation
      resulted in significantly lower peak estradiol levels (mean +/- sd 483.4 +/-
      278.9 vs. 1464.6 +/- 644.9 pg/ml; P < 0.001) and 44% reduction in gonadotropin
      requirement, compared with controls, the length of stimulation, number of embryos
      obtained, and fertilization rates were similar. The human chorionic gonadotropin
      administration criteria had to be adjusted to 20 mm after letrozole stimulation,
      compared with 17-18 mm in the controls. The mean delay from surgery to
      cryopreservation was 38.6 d, with 81% of all patients completing their IVF cycles
      within 8 wk of surgery. CONCLUSION: Ovarian stimulation with letrozole and FSH
      appears to be a cost-effective alternative for fertility preservation in breast
      cancer patients with reduced estrogen exposure, compared with standard IVF. If
      patients are referred promptly, they may undergo embryo or oocyte
      cryopreservation without a delay in chemotherapy.

PMID- 16882753
TI  - Novel fibroblast growth factor receptor 1 mutations in patients with congenital
      hypogonadotropic hypogonadism with and without anosmia.
AB  - CONTEXT: Kallmann syndrome is a clinically and genetically heterogeneous
      disorder. To date, loss-of-function mutations in the genes encoding anosmin-1
      (KAL1) and fibroblast growth factor receptor 1 (FGFR1) have been described in the
      X-linked and autosomal dominant forms of this syndrome, respectively. OBJECTIVE:
      The objective was to investigate genetic defects in the KAL1 and FGFR1 genes in
      patients with congenital isolated hypogonadotropic hypogonadism (IHH). PATIENTS:
      Eighty patients (71 males and nine females) with IHH were studied, of which 30
      were familial. Forty-six of them had olfactory abnormalities. METHODS: The coding
      regions of both KAL1 and FGFR1 genes were amplified and automatically sequenced.
      The KAL1 mutations were investigated only in patients with olfactory
      abnormalities, whereas FGFR1 was studied in the entire group. RESULTS: Two novel
      KAL1 mutations, an intragenic deletion of exons 3-6 and a splicing mutation IVS7
      + 1G>A, were identified in two of 46 patients with Kallmann syndrome. Eight novel
      heterozygous FGFR1 mutations (G48S, L245P, R250W, A343V, P366L, K618fsX654,
      P722S, and V795I) were identified in nine of 80 patients with IHH. Eight of them
      had olfactory abnormalities. Interestingly, the G48S mutation was identified in a
      normosmic IHH patient. Two unrelated females, who carried FGFR1 mutations, had
      anosmia and normal reproductive function. CONCLUSION: We identified novel
      mutations in KAL1 and FGFR1 genes in IHH patients. FGFR1 mutations were
      identified in 17% of the patients with olfactory abnormalities and in one of 34
      normosmic IHH patients. In addition, isolated anosmia was identified in two
      unrelated females as a partial phenotypic manifestation of FGFR1 defects.

PMID- 16882754
TI  - Low social support and poor emotional regulation are associated with increased
      stress hormone reactivity to mental stress in systemic hypertension.
AB  - CONTEXT: There is strong evidence for a physiological hyperreactivity to stress
      in systemic hypertension, but data on associated or potentially moderating
      psychological factors are scarce. OBJECTIVE: The objective of the study was to
      identify psychological correlates of physiological stress reactivity in systemic
      hypertension. DESIGN: This was a cross-sectional, quasi-experimentally controlled
      study. Study participants underwent an acute standardized psychosocial stress
      task combining public speaking and mental arithmetic in front of an audience.
      SETTING: The study was conducted in the population in the state of Zurich,
      Switzerland. SUBJECTS: Subjects included 22 hypertensive and 26 normotensive men
      (mean +/- sem 44 +/- 2 yr). MAIN OUTCOME MEASURES: We assessed the psychological
      measures social support, emotional regulation, and cognitive appraisal of the
      stressful situation. Moreover, we measured salivary cortisol and plasma
      epinephrine and norepinephrine before and after stress and several times up to 60
      min thereafter as well as blood pressure and heart rate. RESULTS: We found poorer
      hedonistic emotional regulation (HER) and lower perceived social support in
      hypertensives, compared with normotensives (P < 0.01). Compared with
      normotensives, hypertensives showed higher cortisol, epinephrine, and
      norepinephrine secretions after stress (P < 0.038) as well as higher systolic and
      diastolic blood pressure (P < 0.001). Cortisol reactivity and norepinephrine
      secretion were highest in hypertensive men with low HER (P < 0.05). In contrast,
      hypertensives with high HER did not significantly differ from normotensives in
      both cortisol and norepinephrine secretion after stress. Epinephrine secretion
      was highest in hypertensives with low social support but was not different
      between hypertensives with high social support and normotensives. CONCLUSIONS:
      The findings suggest that both low social support and low HER are associated with
      elevated stress hormone reactivity in systemic hypertension.

PMID- 16882755
TI  - In brief: fecal overflow incontinence.

PMID- 16882757
TI  - Medication potpourri.

PMID- 16882756
TI  - In brief: hirschsprung disease.

PMID- 16882758
TI  - Media and child health: pediatric care and anticipatory guidance for the
      information age.

PMID- 16882759
TI  - Consultation with the specialist: adolescent idiopathic scoliosis.

PMID- 16882760
TI  - Index of suspicion.

PMID- 16882761
TI  - Hallucinogens.

PMID- 16882762
TI  - Drug interactions.

PMID- 16882763
TI  - Disposition of flavonoids via enteric recycling: structural effects and lack of
      correlations between in vitro and in situ metabolic properties.
AB  - The purpose of this study is to determine the importance of coupling of efflux
      transporters and metabolic enzymes in the intestinal disposition of six
      isoflavones (genistein, daidzein, formononetin, glycitein, biochanin A, and
      prunetin), and to determine how isoflavone structural differences affect the
      intestinal disposition. A rat intestinal perfusion model was used, together with
      rat intestinal and liver microsomes. In the intestinal perfusion model,
      significant absorption and excretion differences were found between isoflavones
      and their respective glucuronides (p <0.05), with prunetin being the most rapidly
      absorbed and formononetin glucuronides being the most excreted in the small
      intestine. In contrast, glucuronides were excreted very little in the colon. In
      an attempt to account for the differences, we measured the glucuronidation rates
      of six isoflavones in microsomes prepared from rat intestine and liver. Using
      multiple regression analysis, intrinsic clearance (CL(int)) and other enzyme
      kinetic parameters (V(max) and K(m)) were determined using appropriate kinetic
      models based on Akaike's information criterion. The kinetic parameters were
      dependent on the isoflavone used and the types of microsomes. To determine how
      metabolite excretion rates are controlled, we plotted excretion rates versus
      calculated microsomal rates (at 10 microM), CL(int) values, K(m) values, or
      V(max) values, and the results indicated that excretion rates were not controlled
      by any of the kinetic parameters. In conclusion, coupling of intestinal metabolic
      enzymes and efflux transporters affects the intestinal disposition of
      isoflavones, and structural differences of isoflavones, such as having methoxyl
      groups, significantly influenced their intestinal disposition.

PMID- 16882764
TI  - Elucidation of the effects of the CYP1A2 deficiency polymorphism in the
      metabolism of 4-cyclohexyl-1-ethyl-7-methylpyrido[2,3-d]pyrimidine-2-(1h)-one (YM
      64227), a phosphodiesterase type 4 inhibitor, and its metabolites in dogs.
AB  - The canine CYP1A2 1117 C>T single nucleotide polymorphism is responsible for a
      substantial portion of the interindividual variability seen in the
      pharmacokinetics of 4-cyclohexyl-1-ethyl-7-methylpyrido[2,3-d]pyrimidine-2-(1H)
      one (YM-64227). The purpose of this study is to investigate the contribution of
      CYP1A2 to the metabolism of YM-64227 and its five metabolites (MM-1 to MM-5), as
      well as to determine the interindividual variability between the pharmacokinetic
      profiles of the compounds with respect to the CYP1A2 deficiency polymorphism.
      alpha-Naphthoflavone and anti-CYP1A1/2 antibody inhibited the metabolic
      activities at which MM-2 and MM-3 were formed from YM-64227 in C/C- and C/T-type
      microsomes. In T/T type, the rate of MM-2 and MM-3 formation was lower, and alpha
      naphthoflavone and anti-CYP1A1/2 antibody were shown to have no effect. A
      positive correlation between the overall metabolism of YM-64227 and phenacetin O
      deethylation, a CYP1A2 activity marker, was observed in all the genotypes. The in
      vitro metabolic clearances in the T/T type of MM-1, MM-3, MM-4, and MM-5 were
      less than 50% lower than those in the C/C type. The anti-CYP1A1/2 antibody
      inhibited the metabolism of MM-1, MM-3, MM-4, and MM-5 in the C/C and C/T types.
      These results suggest that the formation of MM-2 and MM-3 from YM-64227 is
      catalyzed by CYP1A2, and that CYP1A2 contributes mainly to the subsequent
      metabolism of the primary metabolites of YM-64227, with the exception of MM-2. It
      is possible that the interindividual variability of YM-64227 with respect to the
      CYP1A2 deficiency polymorphism is caused by a decrease in the metabolic
      activities of both the unchanged drug and its metabolites.

PMID- 16882765
TI  - Uptake and intracellular binding of lipophilic amine drugs by isolated rat
      hepatocytes and implications for prediction of in vivo metabolic clearance.
AB  - The hepatic uptake of imipramine and propranolol was investigated after
      incubation with isolated rat hepatocytes over a wide concentration range (0.04
      400 microM). The cell-to-medium concentration ratio (K(p)) was concentration
      dependent and could be described using a two-site binding model incorporating a
      high affinity/low capacity site and a linear component for a site which was
      apparently not saturated. Maximum (at 0.04 microM) and minimum K(p) values (at
      400 microM) were 360 and 280, and 110 and 70 for imipramine and propranolol,
      respectively. During these incubations, metabolism was inhibited using
      aminobenzotriazole (an irreversible inhibitor of cytochrome P450). Pretreatment
      of cells either by freeze-thawing or with saponin (which permeabilizes the plasma
      membrane) eliminated the saturable process. The saturable uptake process of
      imipramine was also inhibited by 18 other lipophilic amine drugs (including
      propranolol). This uptake component may involve membrane transporter(s), whereas
      the nonsaturable component probably represents partition into the phospholipid
      component of membranes. Propranolol was further investigated to determine the
      impact of high K(p) values on hepatocellular clearance. The area under the curve
      for propranolol concentrations in the total incubate (medium including the cells)
      from the depletiontime profile was substantially greater than the corresponding
      area under the curve for the drug concentration in the extracellular medium, and
      this difference approximated the nonsaturable uptake component. It is concluded
      that the clearance of propranolol in isolated hepatocytes is not rate-limited by
      hepatic uptake and is directly proportional to unbound drug concentration, being
      independent of the higher K(p) value.

PMID- 16882766
TI  - Synthesis of substituted phenyl diaziridines and characterization as mechanism
      based inactivators of human cytochrome P450 2B6.
AB  - The metabolism of arylhydrazines by cytochromes P450 (P450s) has previously been
      shown to yield aryl-iron complexes that inhibit P450 enzymes as a result of heme
      modification. These modifications of the heme have been used to probe the
      topology of the active site of several P450s. Therefore, diaziridines containing
      one or more substitutions on the phenyl ring were synthesized and evaluated as
      potential mechanism-based inactivators of P450 2B enzymes that could be used to
      elucidate the active site topology. Five of the six trifluoroaryldiaziridines
      tested selectively inactivated P450 2B6 in the reconstituted system in a time-,
      concentration-, and NADPH-dependent manner as measured using the 7-ethoxy-4
      (trifluoromethyl)coumarin O-deethylation assay. The kinetic parameters for P450
      2B6 inactivation by the five compounds were calculated. Analysis of the P450 heme
      from P450s inactivated by the five substituted diaziridines suggested that the
      activity loss was not due to heme destruction as measured by the reduced-CO
      spectrum or high-performance liquid chromatography of the P450 heme. Dialysis
      experiments indicated the irreversible nature of the inactivation and the
      reaction between the diaziridine compounds and the P450 enzyme. Interestingly, a
      thiomethyl-substituted phenyl diaziridine had no effect on the activity of P450
      2B6 in the reconstituted system, but competitively inhibited the O-debenzylation
      activity of P450 3A4 with 7-benzyloxy-4-(trifluoromethyl)coumarin as substrate.
      Binding spectra suggest that this compound bound reversibly to P450 2B6, and
      preliminary results indicate that 3-(4-methylthiophenyl)-3
      (trifluoromethyl)diaziridine is metabolized by P450 2B6.

PMID- 16882767
TI  - Metabolism and disposition of vatalanib (PTK787/ZK-222584) in cancer patients.
AB  - Vatalanib (PTK787/ZK-222584) is a new oral antiangiogenic molecule that inhibits
      all known vascular endothelial growth factor receptors. Vatalanib is under
      investigation for the treatment of solid tumors. Disposition and
      biotransformation of vatalanib were studied in an open-label, single-center study
      in patients with advanced cancer. Seven patients were given a single oral (14)C
      radiolabeled dose of 1,000 mg of vatalanib administered at steady state, obtained
      after 14 consecutive daily oral doses of 1,000 mg of nonradiolabeled vatalanib.
      Plasma, urine, and feces were analyzed for radioactivity, vatalanib, and its
      metabolites. Metabolite patterns were determined by high-performance liquid
      chromatography coupled to radioactivity detection with off-line microplate solid
      scintillation counting and characterized by LC-MS. Vatalanib was well tolerated.
      The majority of adverse effects corresponded to common toxicity criteria grade 1
      or 2. Two patients had stable disease for at least 7 months. Plasma C(max) values
      of (14)C radioactivity (38.3 +/- 26.0 microM; mean +/- S.D., n = 7) and vatalanib
      (15.8 +/- 9.5 microM) were reached after 2 and 1.5 h (median), respectively,
      indicating rapid onset of absorption. Terminal elimination half-lives in plasma
      were 23.4 +/- 5.5 h for (14)C radioactivity and 4.6 +/- 1.1 h for vatalanib.
      Vatalanib cleared mainly through oxidative metabolism. Two pharmacologically
      inactive metabolites, CGP-84368/ZK-260120 [(4-chlorophenyl)-[4-(1-oxy-pyridin-4
      yl-methyl)-phthalazin-1-yl]-amine] and NVP-AAW378/ZK-261557 [rac-4-[(4-chloro
      phenyl)amino]-alpha-(1-oxido-4-pyridyl)phthalazine-1-methanol], having systemic
      exposure comparable to that of vatalanib, contributed mainly to the total
      systemic exposure. Vatalanib and its metabolites were excreted rapidly and mainly
      via the biliary-fecal route. Excretion of radioactivity was largely complete,
      with a radiocarbon recovery between 67% and 96% of dose within 7 days (42-74% in
      feces, 13-29% in urine).

PMID- 16882768
TI  - Childhood bullying involvement and exposure to intimate partner violence.
AB  - OBJECTIVE: Our objectives with this study were to describe the prevalence of
      bullying involvement (ie, bullying and victimization) among children from a
      multigenerational study and to examine the relationship of these childhood
      behaviors and exposure to intimate partner violence. METHODS: A community-based
      cohort of 112 children (aged 6 to 13 years) was asked to self-report on physical,
      verbal, and relational types of bullying and victimization experienced in the
      past year. Parents reported on their child's externalizing and internalizing
      behaviors during the previous 6 months using items from Achenbach's Child
      Behavior Checklist. The frequency of parental experiences of intimate partner
      violence perpetration and victimization at 2 time points during the preceding 5
      years was measured using Conflict Tactics Scale items. The association of
      intimate partner violence and parent-reported child behavioral problems was
      examined, followed by exposure to intimate partner violence and child-reported
      bullying or victimization. Parental risk factors (eg, race/ethnicity, education,
      problem drinking) that predispose to intimate partner violence were controlled
      for using propensity score statistical modeling. RESULTS: Eighty-two (73.2%)
      children reported being victimized by peers, and 38 (33.9%) children reported
      bullying behaviors in the past year. More reports came from girls than from boys
      (55% for victimization and 61% for bullying). Almost all (97%) child bullies were
      also victims themselves. Intimate partner violence was reported by parent
      respondents in 53 (50.5%) households at any or both of the 2 time points.
      Exposure to intimate partner violence was not associated with child-reported
      relational bullying behaviors or victimization by peers, However, intimate
      partner violence-exposed children were at increased risk for problematic levels
      of externalizing behavior/physical aggression and internalizing behaviors.
      CONCLUSIONS: In our sample, children who were 6 to 13 years of age reported a
      substantial amount of bullying and victimization; a large majority were bully
      victims and female. Regression analyses did not show that children who were
      exposed to intimate partner violence were more likely to engage in relational
      bullying. However, children who are exposed to intimate partner violence have a
      higher likelihood of internalizing behaviors and physical aggression.

PMID- 16882769
TI  - Barriers to following the supine sleep recommendation among mothers at four
      centers for the Women, Infants, and Children Program.
AB  - OBJECTIVES: The risk for sudden infant death syndrome in black infants is twice
      that of white infants, and their parents are less likely to place them in the
      supine position for sleep. We previously identified barriers for parents to
      follow recommendations for sleep position. Our objective with this study was to
      quantify these barriers, particularly among low-income, primarily black mothers.
      DESIGN/METHODS: We conducted face-to-face interviews with 671 mothers, 64% of
      whom were black, who attended Women, Infants, and Children Program centers in
      Boston, Massachusetts, Dallas, Texas, Los Angeles, California, and New Haven,
      Connecticut. We used univariate analyses to quantify factors that were associated
      with choice of sleeping position and multivariate logistic regression to
      calculate adjusted odds ratios for the 2 outcome variables: "ever" (meaning
      usually, sometimes, or last night) put infant in the prone position for sleep and
      "usually" put infant in the supine position to sleep. RESULTS: Fifty-nine percent
      of mothers reported supine, 25% side, 15% prone, and 1% other as the usual
      position. Thirty-four percent reported that they ever placed infants in the prone
      position. Seventy-two percent said that a nurse, 53% a doctor, and 38% a female
      friend or relative provided source of advice. Only 42% reported that a nurse,
      only 36% a doctor, and only 15% a female friend or relative recommended the
      supine position for sleep. When a female friend or relative recommended the prone
      position, mothers were more likely ever to place their infants in the prone
      position and less likely usually to choose supine compared with those who
      received no advice from friends or relatives. When a doctor or a nurse
      recommended a nonsupine position, the mothers were less likely to choose supine
      compared with those who received no advice from a doctor or a nurse. Mothers who
      trusted the opinion of a doctor or a nurse about infant sleeping position were
      more likely to place their infants in the supine position. Half of the mothers
      believed that infants were more likely to choke when supine, and they were less
      likely to place their infants supine. Mothers who believed that infants are more
      comfortable in the prone position (36%) were more likely to place their infants
      prone. Twenty-nine percent believed that having their infants sleep with an adult
      helps prevent sudden infant death syndrome, and only 43% believed that sudden
      infant death syndrome is related to sleeping position. CONCLUSIONS: We identified
      specific barriers to placing infants in the supine position for sleep (lack of or
      wrong advice, lack of trust in providers, knowledge and concerns about safety and
      comfort) in low-income, primarily black mothers that should be considered when
      designing interventions to get more infants onto their back for sleep.

PMID- 16882770
TI  - Rotavirus vaccination and intussusception: can we decrease temporally associated
      background cases of intussusception by restricting the vaccination schedule?
AB  - OBJECTIVE: The first rotavirus vaccine that was licensed in the United States,
      RotaShield, could have prevented the enormous burden of rotavirus diarrhea in
      American children but left instead the unfortunate legacy that live oral
      rotavirus vaccines may be associated with a serious but rare adverse event:
      intussusception. Although large trials indicate that the next generation of
      rotavirus vaccines is not associated with this complication, many children likely
      will develop intussusception by chance alone in the 2-week window after
      immunization, raising concerns about whether these cases might be "caused" by the
      vaccine. Our objective for this study was to model and compare the number of
      temporally associated intussusception events that are expected by chance alone
      under 2 rotavirus vaccination strategies. METHODS: We used national vaccine
      coverage rates and age-specific incidence of intussusception by months to model
      the number of temporally associated cases of intussusception that are expected by
      chance alone for 2 potential vaccination strategies: a strict schedule, limiting
      immunization to children within 1 month of the designated age for each dose (ie,
      60-89, 120-149, and 180-209 days for doses 1, 2, and 3, respectively) versus a
      free schedule whereby infants are immunized whenever they appear for their
      routine vaccines up to 1 year of age. RESULTS: The number of intussusception
      events during the 2-week postvaccination window was 24% lower for the strict
      versus the free schedule (138 vs 182, respectively). This reduction was
      attributable largely to the smaller number of infants who were immunized fully
      under the strict schedule (vaccine coverage for 3 doses, 67% vs 89%). The
      cumulative risk for intussusception's occurring by chance in the 2-week
      postvaccination window essentially was the same between schedules (4.59 vs 4.76
      per 100000 doses). Most cases occurred after the second or third dose.
      CONCLUSIONS: Although an age-restricted vaccination schedule substantially
      reduced the number of intussusception events that were observed in the 2-week
      postvaccination window when compared with a schedule with fewer restrictions,
      this decrease was attributable to a lower rate of vaccine coverage rather than a
      safer schedule of vaccination. The risk for intussusception did not differ
      significantly between vaccination strategies. Public health policy and education
      messages for physicians and parents should be developed to anticipate
      intussusception events that will occur by chance alone but are temporally related
      to rotavirus vaccination.

PMID- 16882771
TI  - The relationship between watching professional wrestling on television and
      engaging in date fighting among high school students.
AB  - CONTEXT: Previous research has found that exposure to violence in the home,
      community, and electronic media are associated with children's and adolescents'
      normative expectations concerning the use of violence and with other indicators
      of the violent behaviors by youth. OBJECTIVE: Our purpose with this study was to
      examine the relationships between the frequency that high school students
      reported watching wrestling on television and engaging in date fighting, weapon
      carrying, and other fighting behaviors. DESIGN: The initial analysis consisted of
      a cross-sectional study of a simple random sample of high school students, which
      was followed by a longitudinal analysis of these students over a 6- to 7-month
      period. SETTING: The setting was all public high schools in 1 city/county system.
      PARTICIPANTS: We used a simple random sample (N = 2228) of students. MAIN OUTCOME
      MEASURES: The primary outcome variables included the frequency of date fighting
      during the previous 12 months and alcohol or other drug involvement associated
      with the last date fight. RESULTS: There were significant correlations between
      frequency of watching wrestling on television during the previous 2 weeks and
      engaging in date fighting, fighting in general, and weapon carrying for both
      males and females, although the relationships were stronger among females than
      among males. The frequency of watching wrestling was highest among students
      reporting date fighting when either the victim or perpetrator had been drinking
      alcohol or using illegal drugs. When analyzed using logistic regression, the
      strongest relationships were observed between the frequency of watching wrestling
      and date-fight perpetration among females in cross-sectional and longitudinal
      analyses. These findings persisted after adjusting for multiple other factors.
      CONCLUSIONS: For males and females, the frequency of watching wrestling was
      highest among students who fought with their dates when alcohol or other drugs
      were involved. The association between watching wrestling and date fighting was
      stronger among females than males. The relationship between watching wrestling on
      television and being the perpetrator of dating violence was also stronger among
      females and remained consistent over a 6- to 7-month time period.

PMID- 16882772
TI  - Epidemiology of lawn-mower-related injuries to children in the United States,
      1990-2004.
AB  - OBJECTIVE: Our objective for this study was to describe the epidemiology of lawn
      mower-related injuries among children in the United States. METHODS: A
      retrospective analysis was conducted of data from children who were 20 years and
      younger in the National Electronic Injury Surveillance System of the United
      States Consumer Product Safety Commission for 1990-2004. RESULTS: There were an
      estimated 140700 lawn mower-related injuries to children who were 20 years and
      younger and treated in hospital emergency departments in the United States during
      the 15-year period of 1990-2004. This yielded an average of 9400 injuries
      annually, or 11.1 injuries per 100000 US children per year. The mean age was 10.7
      (SD: 6.0) years, and 78% were boys. The leading type of lawn mower-related injury
      sustained by patients was a laceration (41.2%), followed by soft tissue injury
      (21.4%), burn (15.5%), and fracture (10.3%). The most common body region injured
      was the hand/finger (34.6%), followed by lower extremity (18.9%) and foot/toe
      (17.7%). The eyeball/face and upper extremity accounted for 10.6% and 7.4% of
      injuries, respectively. Burns accounted for 34.5% of injuries to the hand/finger
      compared with 5.5% to other body regions. Ninety-seven percent of amputation
      injuries occurred to the foot/toe (49.5%) and hand/finger (47.5%) compared with
      3% of amputations to other body regions. Burns accounted for 41.8% of injuries
      among children who were < or = 5 years of age compared with 6.5% of injuries to
      children who were older than 5 years. Foreign body injuries accounted for 4.8% of
      injuries among children who were > or = 12 years of age compared with 1.6% of
      injuries to children who were younger than 12 years. Amputations (31.9%),
      lacerations (28.8%), and fractures (26.0%) accounted for almost 87% of injuries
      among children who were admitted or transferred to another hospital. In contrast,
      lacerations (42.3%), soft tissue injuries (23.3%), and burns (16.9%) predominated
      among children who were treated and released to home from the emergency
      department. Children with amputations were more likely to be admitted than
      children with other types of injury. CONCLUSIONS: Injuries related to lawn mowers
      are an important cause of pediatric morbidity. The relative consistency of the
      number of lawn mower-related injuries to children during the 15-year study period
      is evidence that current prevention strategies are inadequate. Passive protection
      that is provided by safer product design is the strategy with the highest
      likelihood of success in preventing these ongoing injuries. The lawn mower
      voluntary safety standard American National Standards Institute/Outdoor Power
      Equipment Institute B71.1-2003 should be revised to include more rigorous
      performance provisions regarding prevention of penetration of feet and toes under
      the mower and into the path of the blades, shielding of hot mower parts from
      access by young children, and equipping all ride-on lawn mowers with a no-mow-in
      reverse default feature with location of its override switch behind the seating
      position of the ride-on mower operator. By locating the no-mow-in-reverse
      override switch behind the ride-on mower operator, the operator would be required
      to look behind the mower before mowing in reverse.

PMID- 16882773
TI  - Escalator-related injuries among children in the United States, 1990-2002.
AB  - OBJECTIVE: We describe the epidemiology of escalator-related injuries among
      children 0 to 19 years of age in the United States, with a focus on the pediatric
      population that is younger than 5 years. METHODS: We conducted a retrospective
      analysis of data from the National Electronic Injury Surveillance System of the
      US Consumer Product Safety Commission. Reported cases were used to project
      national estimates and rates of escalator-related injuries in the United States.
      The analysis included all patients who were 0 to 19 years of age in the National
      Electronic Injury Surveillance System database and were seen in an emergency
      department for an escalator-related injury during the 13-year period 1990-2002.
      RESULTS: There were an estimated 26000 escalator-related injuries among children
      who were 0 to 19 years of age in the United States during 1990-2002, yielding an
      average of 2000 of these injuries annually (rate = 2.6 per 100,000 population per
      year). The mean age was 6.5 years at the time of injury, and 53.4% of the
      patients were male. When comparing cases by 5-year age groups, children who were
      younger than 5 years had the highest estimated number of injuries (12000), as
      well as the highest annual escalator-related injury rate (4.8 per 100000). The
      most common mechanism of injury for all age groups was a fall, accounting for
      13000 (51.0%) injuries. Entrapment accounted for 29.3% of all injuries and 36.5%
      of injuries among children who were younger than 5 years. Six percent (723) of
      injuries to children who were younger than 5 years involved a stroller, with most
      injuries occurring when a child fell out of the stroller while on the escalator.
      The most common body part injured for all ages was the leg, accounting for 27.7%
      of all injuries. Among children who were younger than 5 years, the hand was the
      most common injury site (40.6%), with hand injuries frequently occurring as a
      result of entrapment (72.4%). A laceration was the most common type of injury,
      accounting for 47.4% of escalator-related injuries. Amputations and avulsions
      were uncommon; however, 71.4% (595 of 833) occurred among children who were
      younger than 5 years. CONCLUSIONS: There was a disproportionate number of
      escalator-related injuries among children who were younger than 5 years.
      Entrapment occurred more frequently among children who were younger than 5 years
      than in any other age group, which may explain the increased number of hand
      injuries in this age group. Escalator designs that reduce the gap between the
      steps and sidewall or shield against access to the gap may decrease entrapment
      risk. Young children should be supervised properly and should not be transported
      in a stroller while riding on an escalator. All passengers should use caution and
      remain alert when riding an escalator to avoid injuries related to falls or
      entrapment. Additional research is needed to determine the relationship among
      passenger behavior, escalator design, and escalator-related injury.

PMID- 16882774
TI  - Does maternal control during feeding moderate early infant weight gain?
AB  - OBJECTIVE: Our objective with this study was to examine whether observed maternal
      control during feeding at 6 months of age moderates the development of early
      infant weight gain during the first year of life. METHODS: Sixty-nine women were
      observed feeding their 6-month-old infants during a standard meal. Mealtimes were
      coded for maternal use of controlling feeding behavior. All infants were weighed
      at birth and at 6 and 12 months of age, and weight gain was calculated from birth
      to 6 months and from 6 to 12 months. Weight scores and weight gain scores were
      standardized for prematurity, age, and gender. RESULTS: Infant weight gain
      between 6 and 12 months of age was predicted by an interaction between early
      infant weight gain (birth to 6 months) and observed maternal control during
      feeding at 6 months. When maternal control was moderate or low, there was a
      significant interaction with weight gain from birth to 6 months in the prediction
      of later infant weight gain from 6 to 12 months, such that infants who showed
      slow early weight gain accelerated in their subsequent weight gain, and those
      with greater early weight gain decelerated. Conversely, when maternal control was
      high, infant weight gain followed the opposite pattern. CONCLUSION: Maternal
      control of solid feeding can moderate infant weight gain.

PMID- 16882775
TI  - A mother's feelings for her infant are strengthened by excellent breastfeeding
      counseling and continuity of care.
AB  - OBJECTIVE: Continuous support during the childbirth process ultimately may
      strengthen the mother's self-esteem and her capacity to interact with and nurture
      her infant and also may improve paternal involvement in general. In the present
      study, we investigated whether mothers, who were attended by midwives and nurses
      who had had a process-oriented training program in breastfeeding counseling,
      perceived stronger maternal feelings for their infant than mothers who had
      received only routine care. METHODS: In a previous study, an intervention that
      included a process-oriented program on breastfeeding counseling for health
      professionals and continuity in family classes through childbirth was conducted.
      The 10 largest municipalities were classified in pairs that were similar in size
      and had similar figures of breastfeeding duration. The municipalities were
      randomized pairwise to either an intervention or a control group. The present
      study is a follow-up study on women's feelings for their infants in relation to
      the kind of care that they had had and was undertaken between April 2000 and
      January 2003. The sampling frame was based on women who were cared for at either
      the intervention clinic or control clinics. The mothers at the control clinics
      had received standard routine care and had attended family classes through the
      point of birth. Data collection for control group A started before effects of the
      intervention could be studied. Data for control group B were collected
      simultaneously with data collection for the intervention group (n = 540). The
      mothers responded to 3 questionnaires at 3 days and at 3 and 9 months postpartum.
      Background data of the mothers were collected. The perception of support that was
      provided by the health professionals and the perception of mother-infant
      relationship and feelings for the infant were rated on Likert scales. RESULTS: At
      3 days postpartum, both the intervention group and control group B versus the
      control group A thought that their understanding of the infant was better, they
      perceived more strongly that the infant as their own, and they enjoyed more
      breastfeeding and resting with the infant. Although there was no significant
      difference between the intervention group and control group B at 3 days and 3
      months observation, mothers in the intervention group talked more to their
      infant, perceived their infant to be more beautiful than other infants, and
      perceived more strongly that the infant was their own than did the mothers in
      control group B at 9 months observation. In addition, the mothers in the
      intervention group felt significantly more confident with the infant and felt the
      infant to be closer than did the mothers in control group B. CONCLUSION: A
      process-oriented breastfeeding training program for antenatal midwives and
      postnatal nurses that included an intervention that guaranteed continuity of care
      strengthened the maternal relationship with the infant and the feelings for the
      infant.

PMID- 16882776
TI  - Longitudinal associations between blood lead concentrations lower than 10
      microg/dL and neurobehavioral development in environmentally exposed children in
      Mexico City.
AB  - OBJECTIVE: Increasing evidence suggests that 10 microg/dL, the current Centers
      for Disease Control and Prevention screening guideline for children's blood lead
      level, should not be interpreted as a level at which adverse effects do not
      occur. Using data from a prospective study conducted in Mexico City, Mexico, we
      evaluated the dose-effect relationship between blood lead levels and
      neurodevelopment at 12 and 24 months of age. METHODS: The study population
      consisted of 294 children whose blood lead levels at both 12 and 24 months of age
      were < 10 microg/dL; blood lead levels were measured by graphite furnace atomic
      absorption spectroscopy; Bayley Scales of Infant Development II were administered
      at these ages. The outcomes of interest were the Mental Development Index and the
      Psychomotor Development Index. RESULTS: Adjusting for covariates, children's
      blood lead levels at 24 months were significantly associated, in an inverse
      direction, with both Mental Development Index and Psychomotor Development Index
      scores at 24 months. Blood lead level at 12 months of age was not associated with
      concurrent Mental Development Index or Psychomotor Development Index scores or
      with Mental Development Index at 24 months of age but was significantly
      associated with Psychomotor Development Index score at 24 months. The
      relationships were not altered by adjustment for cord blood lead level or, in the
      analyses of 24-month Mental Development Index and Psychomotor Development Index
      scores, for the 12-month Mental Development Index and Psychomotor Development
      Index scores. For both Mental Development Index and Psychomotor Development Index
      at 24 months of age, the coefficients that were associated with concurrent blood
      lead level were significantly larger among children with blood lead levels < 10
      microg/dL than it was among children with levels > 10 microg/dL. CONCLUSIONS:
      These analyses indicate that children's neurodevelopment is inversely related to
      their blood lead levels even in the range of < 10 microg/dL. Our findings were
      consistent with a supralinear relationship between blood lead levels and
      neurobehavioral outcomes.

PMID- 16882777
TI  - Socioeconomic impact of modern multidisciplinary management of retinoblastoma.
AB  - OBJECTIVE: Our objective for this study was to examine the impact of the modern
      management of intraocular retinoblastoma on the patient and the family. METHODS:
      This study comprises a retrospective, noncomparative case series of 25
      consecutive patients with multifocal, intraocular retinoblastoma that was treated
      with primary systemic chemotherapy. Medical charts were reviewed, and the
      following data were extracted: patients' age and gender, laterality of disease,
      and Reese-Ellsworth classification of each eye as well as the number of central
      venous lines placed, cycles of chemotherapy received, outpatient appointments,
      examinations under anesthesia, focal therapies administered, computed
      tomography/MRI, radiation treatments, anesthetic procedures administered, and
      miles traveled. RESULTS: Twenty patients with bilateral and 5 with unilateral
      intraocular retinoblastoma (median age: 9.3 months) had 895 outpatient
      appointments and underwent 698 examinations under anesthesia with 230 focal
      therapies, 347 days of radiotherapy, 226 computed tomography scans/MRIs, and 38
      central venous line placements. A total of 1272 anesthetic procedures (median:
      50) were performed with no major complication. In all, patients traveled 822312
      miles (median: 22214 miles) to receive their care. The median follow-up was 82
      months. CONCLUSIONS: Successful retinoblastoma management requires close
      surveillance, aggressive consolidation, and numerous anesthetic procedures, all
      of which the patients and the families must endure. There is a significant impact
      on the patient, the family, and hospital resources.

PMID- 16882778
TI  - Family and physician influence on asthma research participation decisions for
      adolescents: the effects of adolescent gender and research risk.
AB  - OBJECTIVE: There is considerable ethical and legal ambiguity surrounding the role
      of adolescents in the decision-making process for research participation.
      Depending on the nature of the study and the regulations involved, adolescents
      may have independent responsibility for providing informed consent, they may be
      asked to provide their assent, or they may be completely excluded from the
      decision-making process. This study examined parent and adolescent perceptions of
      decision-making authority and sources of influence on adolescent research
      participation decisions, and examined whether perceptions of influence differed
      based on adolescent gender and level of research risk. STUDY DESIGN: Adolescents
      (n = 36) with asthma and their parents reviewed 9 pediatric research protocols,
      decided whether they would choose to participate, rated the extent they would be
      responsible for the actual decision, and indicated the ability of family and
      physician to influence their decisions. Multivariate analyses of variance were
      used to evaluate differences in perceptions of decision-making authority and
      sources of influence on the decisions. RESULTS: Adolescents were less willing to
      cede decision making authority to parents than parents anticipated. Parents and
      adolescents acknowledged a greater openness to influence from physicians than
      from family for above minimal risk studies. Parents were more willing to consider
      opinions from male adolescents. CONCLUSIONS: Adolescents desire responsibility
      for research participation decisions, though parents may not share these views.
      Physicians' views on research participation are important to families, especially
      for above minimal risk studies. Parents may grant more decision-making autonomy
      to adolescent males than to females. Researchers, physicians, and institutions
      play a key role in facilitating the ethical enrollment of adolescents into
      biomedical research. Educational, policy, and oversight processes that support
      both adolescent autonomy and parental responsibility for research participation
      decision-making in biomedical research are discussed.

PMID- 16882779
TI  - Asthma prevalence in Hispanic and Asian American ethnic subgroups: results from
      the California Healthy Kids Survey.
AB  - OBJECTIVES: Asthma prevalence for different ethnic groups in the United States,
      beyond white, black and Hispanic, is seldom reported. We compared the prevalence
      of asthma diagnosis among various Hispanic and Asian American ethnic subgroups
      using data collected from the school-based California Healthy Kids Survey.
      METHODS: The California Healthy Kids Survey was administered to 462 147 public
      school students in the seventh, ninth, and 11th grades throughout California
      during the 2001-2002 and 2002-2003 school years. Prevalence of lifetime asthma
      diagnosis was calculated for 11 Asian American Pacific Islander subgroups and 8
      Hispanic subgroups. RESULTS: Asthma prevalence among Hispanic subgroups ranged
      from 13.2% for Mexican American students to 22.8% for Puerto Rican students and
      23.0% among Cuban American students. Lifetime asthma diagnosis among the 11 Asian
      American Pacific Islander subgroups ranged from 10.9% among Korean American
      students to 23.8% among Filipino American students. CONCLUSIONS: The survey
      revealed substantial variation in asthma prevalence between the different
      Hispanic and Asian American Pacific Islander subgroups and that Pacific
      Islanders, Filipinos, Cubans, and Puerto Ricans are at elevated risk for asthma.
      Differences in the distributions of characteristics related to country of birth,
      residential history, generational status, and/or degree of acculturation might
      account for much of the observed differences in asthma prevalence between ethnic
      subgroups. Previous asthma prevalence estimates for Asians or Hispanics are in
      part a function of the particular ethnic composition of the population under
      investigation. We suggest that asthma studies that include a substantial number
      of Asian Pacific Islander and Hispanic persons use a more detailed categorization
      of race/ethnicity.

PMID- 16882780
TI  - Increased risk of precocious puberty in internationally adopted children in
      Denmark.
AB  - BACKGROUND: Studies have indicated that internationally adopted children have an
      increased risk of developing precocious puberty, but no epidemiologic risk
      estimates have previously been calculated. We aimed to assess the risk of
      developing precocious puberty in intercountry adoptees, children immigrating with
      their family, and descendants of immigrants living in Denmark. METHODS: Patients
      who were registered with the diagnosis of precocious puberty during the period
      1993-2001 were identified through the national patient registry. The background
      population of children born from 1983 to 2001 were identified through the unique
      Danish Civil Registration System and subsequently categorized as being Danish (N
      = 1,062,333), adopted (N = 10,997), immigrating with their family (N = 72,181),
      or being descendants of immigrants (N = 128,152). The incidence rate ratio of
      precocious puberty was estimated by log-linear Poisson regression. All rate
      ratios were adjusted for age and its interaction with gender and calendar year. P
      values were based on likelihood ratio tests, and 95% confidence intervals were
      calculated by Wald's test. RESULTS: In the study period, 655 children developed
      precocious puberty during 5,627,763 person-years at risk. Adopted children were
      followed during 39,978 person-years at risk, during which 45 girls and 6 boys
      developed precocious puberty. The risk of developing precocious puberty was
      significantly increased 10 to 20 times in adopted girls compared with girls with
      Danish background. The risk of developing precocious puberty depended on the
      country of origin. In children immigrating with their family, the risk of
      developing precocious puberty was only marginally increased. Older age at
      adoption significantly increased the risk of precocious puberty in adoptees
      independent of region of origin. The incidence rate ratio was significantly
      higher in children adopted after the age of 2. In children immigrating with their
      family, we found no effect of age at migration. DISCUSSION: In this large,
      nationwide, register-based study including 655 cases of precocious puberty, we
      found that intercountry boys and girls were 10 to 20 times more likely to develop
      precocious puberty compared with the Danish reference group. Older age at
      adoption significantly increased the risk of precocious puberty. Uncertainty of
      the exact age is a well-known problem in adopted children, and systematic
      underestimation of age might bias the result. However, using the worst-case
      scenario that all children who according to the Danish Civil Registration System
      were adopted after 2 years of age were in fact 1 year older, we still observed a
      highly increased risk of precocious puberty associated with adoption and
      especially with adoption after 2 years of age. Surprisingly, the risk of
      precocious puberty was not increased in the large group of children adopted from
      Korea. One case of precocious puberty was identified among Korean children,
      whereas > 20 cases of precocious puberty would have been expected if the risk for
      a Korean child was at the same level as observed among adopted children from
      India and South America. In the study population, 99% of Korean children were
      adopted before 2 years of age, which may contribute to explaining our finding. In
      Korea, children appointed for adoption are often living in foster care settings
      from birth to adoption, whereas most other countries are reported to take care of
      the children in orphanages before adoption. It can only be speculated whether a
      relation between preadoption living conditions and later risk of precocious
      puberty exists. Genetic factors play a key role in the timing of puberty, and
      large variations in age at menarche are observed worldwide. Age at menarche is
      reported to be in the same age range in South Korea as in well-off populations in
      other parts of the world, indicating that the different risk of precocious
      puberty observed between Korean and other adoptees probably cannot be explained
      by genetic factors alone. The finding that the risk of precocious puberty was
      significantly increased among adoptees in contrast to what was seen in children
      immigrating with their families contradicts a direct effect of migration. An
      increasing number of studies have shown long-term effects of certain prenatal and
      postnatal growth patterns, including advancement in pubertal maturation after
      poor intrauterine growth and catch-up growth during childhood. Different growth
      patterns and dietary habits between adoptees and children immigrating with their
      families might contribute to explain our findings. It has been hypothesized that
      stressful psychosocial factors in infancy and childhood may lead to earlier
      pubertal maturation. In general, adoptees have experienced several traumatic life
      events, and it may be speculated that these events alter the susceptibility for
      developing precocious puberty. CONCLUSIONS: Foreign-adopted children originating
      from regions other than Korea had a 15- to 20-fold increased risk of precocious
      puberty compared with Danish-born children, whereas adoptees originating from
      Korea had no increased risk of precocious puberty. In addition, children
      immigrating with their families had no increased risk of precocious puberty. The
      effect of country of origin might be explained by genetic factors or by different
      environmental exposures and living conditions in the different countries. Older
      age at adoption increased the risk for premature onset of puberty, which may
      suggest that environmental factors influence the risk of precocious pubertal
      development in adopted children.

PMID- 16882781
TI  - Characterization of dermatoglyphics in PHOX2B-confirmed congenital central
      hypoventilation syndrome.
AB  - OBJECTIVE: Individuals with congenital central hypoventilation syndrome have
      characteristic variants in the PHOX2B gene (primarily polyalanine expansion
      mutations). The PHOX2B gene acts as a transcriptional activator in the promotion
      of pan-neuronal differentiation in the autonomic nervous system during early
      embryologic development, with a primary role in the sympathetic noradrenergic
      phenotype in vertebrates. Because sympathetic innervation has been hypothesized
      to affect the development of dermatoglyphic pattern types, we hypothesized that
      individuals with PHOX2B-confirmed congenital central hypoventilation syndrome
      would have characteristic dermatoglyphic patterning and that the dermatoglyphic
      phenotype would be related to the disease-defining PHOX2B genotype. METHODS:
      Dermatoglyphic pattern type frequency, left/right symmetry, and
      genotype/phenotype correlation were assessed for 33 individuals with PHOX2B
      confirmed congenital central hypoventilation syndrome and compared with published
      control data. RESULTS: Dermatoglyphic pattern type frequencies were altered in
      congenital central hypoventilation syndrome cases versus controls. In particular,
      there was an increase of arches in females and ulnar loops in males, with the
      largest differences for the left hand and for individuals with both congenital
      central hypoventilation syndrome and Hirschsprung disease. Dissimilarity scores
      between the congenital central hypoventilation syndrome and congenital central
      hypoventilation syndrome + Hirschsprung disease cases were not significantly
      different, nor were dissimilarity scores between all of the female and all of the
      male cases. No significant association was found between the number of
      polyalanine repeats in the PHOX2B genotypic category and dermatoglyphic pattern
      frequencies in the congenital central hypoventilation syndrome study groups.
      CONCLUSIONS: These results represent the first report describing specific
      dermatoglyphic patterning in congenital central hypoventilation syndrome and
      suggest a relationship between PHOX2B and the expression of dermatoglyphic
      pattern types. An expanded congenital central hypoventilation syndrome data set
      to include the full spectrum of PHOX2B mutations is necessary to further
      delineate the role of PHOX2B in dermatoglyphic patterning.

PMID- 16882782
TI  - Fetal tricuspid valve size and growth as predictors of outcome in pulmonary
      atresia with intact ventricular septum.
AB  - OBJECTIVE: Pulmonary atresia with intact ventricular septum is a complex
      congenital cardiovascular anomaly that frequently requires single ventricle
      palliation. Fetal diagnosis of pulmonary atresia with intact ventricular septum
      is common, but the natural history of pulmonary atresia with intact ventricular
      septum diagnosed in midgestation, predictors of neonatal anatomy, and predictors
      of biventricular repair have not been determined. The objective of this study was
      to determine whether the size and rate of growth of the fetal tricuspid valve
      predict neonatal anatomy and biventricular repair. DESIGN AND RESULTS: Twenty
      three fetuses diagnosed with pulmonary atresia with intact ventricular septum
      between 1990 and 2004 were studied. Of 13 fetuses with a midgestation fetal
      tricuspid valve z score < or = -3, 1 achieved biventricular repair, compared with
      5 of 5 with a tricuspid valve z score > -3. Of 13 fetuses with a midgestation
      fetal tricuspid valve z score < or = -3, 8 were diagnosed postnatally with a
      right ventricular dependent coronary circulation, compared with none with a
      tricuspid valve z score > -3. Midgestation and late gestation fetal tricuspid
      valve z scores correlated with neonatal tricuspid valve z score. The average rate
      of tricuspid valve growth between mid- and late fetal echocardiograms was
      significantly lower in patients who did not achieve biventricular repair than in
      those who did (0.012 +/- 0.008 cm per week vs 0.028 +/- 0.014 cm per week).
      CONCLUSIONS: Fetal tricuspid valve z score and rate of growth predict postnatal
      outcome in pulmonary atresia with intact ventricular septum. These findings may
      have important implications for prenatal counseling and selection of patients for
      fetal pulmonary valve dilation.

PMID- 16882783
TI  - The Alaska Haemophilus influenzae type b experience: lessons in controlling a
      vaccine-preventable disease.
AB  - OBJECTIVE: Before 1991, Alaska Native children experienced one of the highest
      rates of invasive Haemophilus influenzae type b disease. H influenzae type b
      vaccine has led to a near-elimination of invasive H influenzae type b disease in
      the United States. We describe challenges encountered in controlling H influenzae
      type b disease in Alaska and update the current status of H influenzae disease
      and carriage in Alaska as lessons to other populations. PATIENTS AND METHODS: We
      reviewed data from statewide H influenzae disease surveillance conducted during
      1980-2004. Vaccine coverage data were based on audits from tribal facilities and
      the National Immunization Survey. H influenzae type b colonization data were
      based on 6 carriage studies. RESULTS: After universal infant vaccination in 1991,
      H influenzae type b disease among Alaska Native and non-Native children < 5 years
      of age decreased by 94% and 96%, respectively. After a 1996 change in H
      influenzae type b vaccine from polyribosylribitol phosphate-outer membrane
      protein conjugate vaccine to H influenzae type b oligosaccharide-CRM197 vaccine,
      the incidence of H influenzae type b disease increased in rural Alaska Natives
      from 19.8 to 91.1 cases per 100000 per year < 5 years of age. During 2001-2004,
      with use of polyribosylribitol phosphate-outer membrane protein conjugate
      vaccine, the rate of H influenzae type b disease in Alaska Native and non-Native
      children aged < 5 years decreased to 5.4 and 0 per 100000 per year, respectively.
      In postvaccine studies, H influenzae type b carriage has decreased in Alaska
      Native children < 5 years of age. CONCLUSIONS: H influenzae type b vaccination
      has resulted in a dramatic decrease in invasive H influenzae type b disease in
      Alaska; however, despite high rates of H influenzae type b vaccine coverage, H
      influenzae type b disease rates among rural Alaska Native children < 5 years of
      age remain higher than the rates among non-Native Alaska and other US children.
      Equity in disease rates may not be achieved in indigenous populations with the
      current vaccines unless other environmental and household factors contributing to
      disease transmission are addressed.

PMID- 16882784
TI  - Exposure to degrading versus nondegrading music lyrics and sexual behavior among
      youth.
AB  - BACKGROUND: Early sexual activity is a significant problem in the United States.
      A recent survey suggested that most sexually experienced teens wish they had
      waited longer to have intercourse; other data indicate that unplanned pregnancy
      and sexually transmitted diseases are more common among those who begin sexual
      activity earlier. Popular music may contribute to early sex. Music is an integral
      part of teens' lives. The average youth listens to music 1.5 to 2.5 hours per
      day. Sexual themes are common in much of this music and range from romantic and
      playful to degrading and hostile. Although a previous longitudinal study has
      linked music video consumption and sexual risk behavior, no previous study has
      tested longitudinal associations between the content of music lyrics and
      subsequent changes in sexual experience, such as intercourse initiation, nor has
      any study explored whether exposure to different kinds of portrayals of sex has
      different effects. DESIGN AND PARTICIPANTS: We conducted a national longitudinal
      telephone survey of 1461 adolescents. Participants were interviewed at baseline
      (T1), when they were 12 to 17 years old, and again 1 and 3 years later (T2 and
      T3). At all of the interviews, participants reported their sexual experience and
      responded to measures of more than a dozen factors known to be associated with
      adolescent sexual initiation. A total of 1242 participants reported on their
      sexual behavior at all 3 time points; a subsample of 938 were identified as
      virgins before music exposure for certain analyses. Participants also indicated
      how frequently they listened to each of more than a dozen musical artists
      representing a variety of musical genres. Data on listening habits were combined
      with results of an analysis of the sexual content of each artist's songs to
      create measures of exposure to 2 kinds of sexual content: degrading and
      nondegrading. OUTCOME MEASURES: We measured initiation of intercourse and
      advancement in noncoital sexual activity level over a 2-year period. RESULTS:
      Multivariate regression analyses indicated that youth who listened to more
      degrading sexual content at T2 were more likely to subsequently initiate
      intercourse and to progress to more advanced levels of noncoital sexual activity,
      even after controlling for 18 respondent characteristics that might otherwise
      explain these relationships. In contrast, exposure to nondegrading sexual content
      was unrelated to changes in participants' sexual behavior. CONCLUSION: Listening
      to music with degrading sexual lyrics is related to advances in a range of sexual
      activities among adolescents, whereas this does not seem to be true of other
      sexual lyrics. This result is consistent with sexual-script theory and suggests
      that cultural messages about expected sexual behavior among males and females may
      underlie the effect. Reducing the amount of degrading sexual content in popular
      music or reducing young people's exposure to music with this type of content
      could help delay the onset of sexual behavior.

PMID- 16882785
TI  - Brain developmental abnormalities in Prader-Willi syndrome detected by diffusion
      tensor imaging.
AB  - OBJECTIVE: The purpose of this work was to detect brain developmental
      abnormalities in Prader-Willi syndrome by using diffusion tensor imaging based on
      a high-field MRI system. METHODS: Eight patients with Prader-Willi syndrome and 8
      age- and gender-matched normal control subjects were examined using a high-field
      (3.0 T) MRI system. Trace value and fractional anisotropy were assessed
      simultaneously in multiple representative brain regions: the deep gray matter
      (putamen, caudate head, and dorsomedial thalamus) and the white matter structures
      (frontal and parietal white matter, posterior limb of internal capsule, and
      corpus callosum). RESULTS: In Prader-Willi syndrome patients, trace value was
      found to be significantly higher in the left frontal white matter and the left
      dorsomedial thalamus, whereas fractional anisotropy was significantly reduced in
      the posterior limb of the internal capsule bilaterally, the right frontal white
      matter, and the splenium of the corpus callosum. The observed diffusivity
      characteristics indicate developmental abnormalities in these areas, which are
      highly consistent with the clinical features of Prader-Willi syndrome.
      CONCLUSIONS: The study provides the first objective evidence that Prader-Willi
      syndrome patients indeed have developmental abnormalities in specific areas of
      the brain, providing a new window toward understanding the pathophysiology of
      Prader-Willi syndrome.

PMID- 16882786
TI  - Emotional, behavioral, social, and academic outcomes in adolescents born with
      very low birth weight.
AB  - BACKGROUND: Very low birth weight survivors are at increased risk of developing
      emotional and behavioral problems and low social and academic competencies.
      Information on such problems in very low birth weight adolescents is still
      sparse. OBJECTIVES: Our purpose for this work was to study gender-specific
      emotional and behavioral problems and social and academic competencies in a
      cohort of very low birth weight adolescents in north Norway. METHODS: Families
      with very low birth weight adolescents aged 13 to 18 years, born between 1978 and
      1989 (n = 162) were addressed by mail and asked to complete the Child Behavior
      Check List and the Youth Self-Report. Data were compared with 2 normative
      adolescent populations (Child Behavior Check List, n = 540; Youth Self-Report, n
      = 2522). Scores given by very low birth weight adolescents and their parents on
      identical items in Child Behavior Check List and Youth Self-Report (cross
      informant syndrome constructs) were compared in pairs. To explore predictive
      effects, demographic and early medical characteristics were entered into a
      hierarchical multiple regression analysis. RESULTS: There were 156 eligible
      families, and 99 (63.5%) responded. All completed the Child Behavior Check List,
      and 82 (52.6%) completed the Youth Self-Report. Very low birth weight boys
      reported less externalizing and internalizing behaviors and thought and attention
      problems and higher activity score, whereas very low birth weight girls reported
      less externalizing behavior and less social, thought, and attention problems and
      higher activity score compared with normative adolescents. Very low birth weight
      parents, however, reported more social and attention problems and less social and
      school competence in boys and more internalizing behavior and social and
      attention problems and less school competence in girls compared with normative
      parents. They scored high proportions of both genders within the
      borderline/clinical range on all of the scales, except for externalizing behavior
      and social problems in girls. Female very low birth weight adolescents, in
      contrast to males, reported more problems than parents when compared in pairs,
      and externalizing problems in particular were not recognized by parents.
      CONCLUSIONS: From parents' point of view, significant proportions of very low
      birth weight adolescents experience more emotional and behavioral problems and
      less competence than normative adolescents. In contrast, very low birth weight
      adolescents state less problems and similar or higher competence than normative
      adolescents. Very low birth weight adolescent girls report more emotional and
      behavioral problems compared with their parents than very low birth weight
      adolescent boys do. Externalizing problems in very low birth weight adolescent
      girls are often not recognized by parents. To better understand these seemingly
      paradoxical findings and to develop adequate intervention programs, there is a
      need for prospective longitudinal studies.

PMID- 16882787
TI  - Smoking rates and the state of smoking interventions for children and adolescents
      with chronic illness.
AB  - Engaging in smoking is particularly risky for children and adolescents with
      chronic illness whose health status is already compromised because of disease-
      and treatment-related complications. Yet, some of these youngsters smoke at rates
      at least comparable to those of their healthy peers. To date, few randomized
      smoking-prevention and cessation trials have been conducted in children with
      chronic medical problems. In this review we report on the smoking rates among
      youngsters with chronic illness, identify specific disease- and treatment-related
      complications that can be exacerbated by smoking, examine risk factors associated
      with tobacco use among medically compromised youngsters, and review smoking
      interventions that have been conducted to date with pediatric populations in the
      health care setting. The following chronic illnesses are included in this review:
      asthma, cystic fibrosis, cancer, sickle cell disease, juvenile-onset diabetes,
      and juvenile rheumatoid arthritis. Objectives for a tobacco-control agenda and
      recommendations for future tobacco studies in chronically ill pediatric
      populations are provided. Finally, tobacco counseling strategies are suggested
      for clinicians who treat these youngsters in their practices.

PMID- 16882788
TI  - Consensus statement on management of intersex disorders. International Consensus
      Conference on Intersex.

PMID- 16882789
TI  - Deaths resulting from hypocalcemia after administration of edetate disodium: 2003
      2005.
AB  - From 2003 to 2005, deaths of 3 individuals as a result of cardiac arrest caused
      by hypocalcemia during chelation therapy were reported to the Centers for Disease
      Control and Prevention. Two were children, both of whom were treated with edetate
      disodium. At the time of this writing, the adult case was still under
      investigation. No previous cases of death resulting from hypocalcemia during
      chelation have been reported. From our experience and review of the literature,
      we suggest that health care providers who are unfamiliar with chelation consult
      an expert before undertaking treatment and that hospital formularies evaluate
      whether stocking edetate disodium is necessary, given the risk for hypocalcemia
      and the availability of less toxic alternatives.

PMID- 16882791
TI  - Shopping-cart-related injuries to children.
AB  - An estimated 24,200 children younger than 15 years, 20,700 (85%) of whom were
      younger than 5 years, were treated in US hospital emergency departments in 2005
      for shopping cart-related injuries. Approximately 4% of shopping cart-related
      injuries to children younger than 15 years require admission to the hospital.
      Injuries to the head and neck represent three fourths of all injuries. Fractures
      account for 45% of all hospitalizations. Deaths have occurred from falls from
      shopping carts and cart tip-overs. Falls are the most common mechanism of injury
      and account for more than half of injuries associated with shopping carts. Cart
      tip-overs are the second most common mechanism, responsible for up to one fourth
      of injuries and almost 40% of shopping cart-related injuries among children
      younger than 2 years. Public-awareness initiatives, education programs, and
      parental supervision, although important, are not enough to prevent these
      injuries effectively. European Standard EN 1929-1:1998 and joint Australian/New
      Zealand Standard AS/NZS 3847.1:1999 specify requirements for the construction,
      performance, testing, and safety of shopping carts and have been implemented as
      national standards in 21 countries. A US performance standard for shopping carts
      (ASTM [American Society for Testing and Materials] F2372-04) was established in
      July 2004; however, it does not adequately address falls and cart tip-overs,
      which are the leading mechanisms of shopping cart-related injuries to children.
      The current US standard for shopping carts should be revised to include clear and
      effective performance criteria for shopping cart child-restraint systems and cart
      stability to prevent falls from carts and cart tip-overs. This is imperative to
      decrease the number and severity of shopping cart-related injuries to children.
      Recommendations from the American Academy of Pediatrics regarding prevention of
      shopping cart-related injuries are included in the accompanying policy statement.

PMID- 16882790
TI  - Primary hyperparathyroidism mimicking vaso-occlusive crises in sickle cell
      disease.
AB  - We report a case of bone pain associated with primary hyperparathyroidism in a
      patient with sickle cell disease. A 17-year-old girl with sickle cell disease (SS
      phenotype) was seen for bilateral knee and back pain. She had had recurrent
      severe vaso-occlusive crises and acute chest syndrome in the course of her
      disease. In the last 2 years, she had frequent visits to the emergency department
      for severe bone pain. She complained of long-standing fatigue and lethargy. Her
      physical examination was normal. Hydroxyurea treatment, as well as and long- and
      short-acting narcotics were given, with little improvement in symptoms. Poor
      compliance with medication, family dysfunction, and potential narcotic addiction
      were felt to be significant contributors to the patient's symptoms. She was
      incidentally found to have an extremely elevated total calcium level of 3.19
      mmol/L (range: 2.25-2.76) with an ionized calcium level of 1.9 mmol/L (range:
      1.15-1.35). Phosphorus level was 0.82 mmol/L (range: 0.90-1.50), alkaline
      phosphatase level was elevated at 519 U/L (range: 10-170), and parathyroid
      hormone level was extremely high at 1645 pg/mL (range: 10-60). Her renal function
      was normal. Ultrasonography of the neck and a Sestamibi scan revealed a single
      left inferior parathyroid adenoma adjacent to the thyroid lobe. There was no
      evidence of an underlying multiple endocrine neoplasia. The patient was diagnosed
      with primary hyperparathyroidism. Fluid hydration, hydrocortisone, calcitonin,
      and bisphosphonates were initiated for acute hypercalcemia management before
      surgical excision of the left parathyroid adenoma. On review of previous blood
      work, a borderline calcium level of 2.72 was present 18 months before this
      admission. Two years postsurgery, she has normal renal function, calcium, and
      parathyroid hormone levels. The weekly visits to the emergency department for
      pain episodes decreased to 1 every 2 months within the first few months after her
      surgery. The decrease in pain episodes, even if it coincided with the treatment
      of primary hyperparathyroidism, may still reflect the natural evolution of sickle
      cell disease in this patient. However, the high morbidity associated with primary
      hyperparathyroidism was successfully prevented in this patient. Primary
      hyperparathyroidism is rare in childhood. In a recent study, it occurred more
      commonly in female adolescents and was because of a single adenoma, as in our
      patient. Significant morbidity, mainly secondary to renal dysfunction, was
      because of the delay in diagnosis after the onset of symptoms (2.0-4.2 years),
      emphasizing the need for a rapid diagnosis. Sickle cell disease affects
      approximately 1 of every 600 blacks in North America. Acute episodes of severe
      vaso-occlusive crisis account for > 90% of sickle cell-related hospitalizations
      and are a significant cause of morbidity in patients. There is no known
      association between sickle cell disease and primary hyperparathyroidism, and this
      case is most probably a random occurrence. However, as emphasized by this case
      report, pain may also be a harbinger of other disease processes in sickle cell
      disease. Because management may vary, we suggest that care providers consider the
      diagnosis of vaso-occlusive crisis as the diagnosis of exclusion and that other
      etiologies for pain be envisaged in this patient population, especially in the
      presence of prolonged pain or unusual clinical, radiologic, or biological
      findings.

PMID- 16882792
TI  - AAP parent page. Shopping-cart safety.

PMID- 16882794
TI  - State newborn screening in the tandem mass spectrometry era: more tests, more
      false-positive results.
AB  - BACKGROUND: The advent of tandem mass spectrometry has made it possible to test
      newborns for multiple conditions efficiently. It is not known how state newborn
      screening programs have changed screening practices in response to this
      technology and how it affects the number of false-positive test results. METHODS:
      We obtained data from the National Newborn Screening and Genetics Resource Center
      regarding the screening practices for each of the 50 states, to determine the
      number of mandated disorders added to state newborn screening panels between 1995
      and 2005. Combining these data with reported specificities from the literature
      and the number of births in each state, we estimated the number of infants who
      would have received false-positive results through screening with tandem mass
      spectrometry in 2005. RESULTS: The average state mandated screening for 5
      disorders in 1995 (range: 0-8 disorders). Wyoming was the only state that
      decreased its panel size over the next decade. Kansas and Texas were the only
      states that did not add disorders to their panels between 1995 and 2005; the
      average state added 19. Iowa, Minnesota, Mississippi, South Dakota, and Tennessee
      each added > or = 40 disorders. Assuming that an individual test for a disorder
      had a specificity of 99.995%, we estimated that approximately 2575 infants would
      have received false-positive results through screening with tandem mass
      spectrometry in 2005. If specificity was assumed to be 99.9%, then the number
      increased to > 51000. CONCLUSIONS: State newborn screening programs have expanded
      dramatically in the past decade. Because the benefit of such testing may be
      unclear in some cases and because the number of infants who may receive false
      positive results and may be labeled falsely as having disease is potentially
      sizeable, a more cautious approach is needed.

PMID- 16882793
TI  - Variations in management of common inpatient pediatric illnesses: hospitalists
      and community pediatricians.
AB  - OBJECTIVE: The goal was to test the hypothesis that pediatric hospitalists use
      evidence-based therapies and tests more consistently in the care of inpatients
      and use therapies and tests of unproven benefit less often, compared with
      community pediatricians. METHODS: A national survey was administered to
      hospitalists and a random sample of community pediatricians. Hospitalists and
      community pediatricians reported their frequency of use of diagnostic tests and
      therapies, on 5-point Likert scales (ranging from never to almost always), for
      common inpatient pediatric illnesses. Responses were compared in univariate and
      multivariable logistic regression analyses controlling for gender, race, years
      out of residency, days spent attending per year, hospital practice type, and
      completion of fellowship/postgraduate training. RESULTS: Two hundred thirteen
      pediatric hospitalists and 352 community pediatricians responded. In
      multivariable regression analyses, hospitalists were significantly more likely to
      report often or almost always using the following evidence-based therapies for
      asthma: albuterol and ipratropium in the first 24 hours of hospitalization. After
      the first urinary tract infection, hospitalists were more likely to report
      obtaining the recommended renal ultrasound and voiding cystourethrogram.
      Hospitalists were significantly more likely than community pediatricians to
      report rarely or never using the following therapies of unproven benefit:
      levalbuterol, inhaled steroid therapy, and oral steroid therapy for
      bronchiolitis; stool culture and rotavirus testing for gastroenteritis; and
      ipratropium after 24 hours of hospitalization for asthma. CONCLUSION: Overall, in
      comparison with community pediatricians, hospitalists reported greater adherence
      to evidence-based therapies and tests in the care of hospitalized patients and
      less use of therapies and tests of unproven benefit.

PMID- 16882795
TI  - How safe is triage by an after-hours telephone call center?
AB  - OBJECTIVES: Our goals were to assess (1) compliance with nurse disposition
      recommendations, (2) frequency of death or potential underreferral associated
      with hospitalization within 24 hours after a call, and (3) factors associated
      with potential underreferral, for children receiving care within an integrated
      health care delivery organization who were triaged by a pediatric after-hours
      call center. METHODS: The study population included all pediatric patients
      enrolled in Kaiser Permanente Colorado whose families called the Children's
      Hospital after-hours call center in Denver, Colorado, during the period between
      October 1, 1999, and March 31, 2003. Postcall disposition recommendations were
      categorized as urgent (visit within 4 hours), next day (visit in > 4 hours but
      within 24 hours), later visit (visit in > 24 hours), or home care (care at home
      without a visit). Compliance with the nurses' triage disposition recommendations
      was calculated as the proportion of cases for which utilization data matched the
      disposition recommendations. RESULTS: Of the 32,968 eligible calls during the
      study period, 21% received urgent, 27% next day, 4% later visit, and 48% home
      care disposition recommendations. Rates of compliance with both urgent and home
      care disposition recommendations were 74%, and the rate of compliance with next
      day recommendations was 44%. No deaths occurred within < 1 week after the after
      hours calls. The rate of potential underreferral with subsequent hospitalization
      was 0.2%, or 1 case per 599 triaged calls. In multivariate modeling, age of < 6
      weeks or > 12 years and being triaged after 11 pm were associated with higher
      rates of potential under-referral. CONCLUSIONS: Approximately three fourths of
      families complied with recommendations for their child to be evaluated urgently
      or to be treated at home, with much lower rates of compliance with intermediate
      dispositions. The rate of potential underreferral with hospitalization was low,
      and age and time of call triage were associated with this outcome.

PMID- 16882796
TI  - What pediatricians should know about child-related malpractice payments in the
      United States.
AB  - OBJECTIVE: The purpose of this study was to examine child-related National
      Practitioner Data Bank data. METHODS: Data were obtained from the National
      Practitioner Data Bank. RESULTS: the period from February 1, 2004, through
      December 31, 2005, a total of 30195 malpractice payments were made on behalf of
      practitioners in the United States; 14% of those payments (4107 of 30,195
      payments) were child related. During the period analyzed, $1.73 billion were paid
      for malpractice cases involving children. More than 95% of all payments were the
      result of settlements and only approximately 5% the result of judgments. The
      average child-related malpractice payment was significantly greater than an adult
      related malpractice payment ($422,000 vs $247,000); however, child-related
      malpractice payments were only one half as likely to occur, compared with adult
      related malpractice payments. Significant geographic variability was found in the
      numbers and sizes of child-related malpractice payments. Failure to diagnose was
      the leading reason for child-related payments (18%), followed by improper
      performance (9%), delay in diagnosis (9%), and improper management (6%). Finally,
      we found that approximately 40% of all malpractice awards were the result of
      surgical or obstetrical issues. CONCLUSIONS: Practicing pediatricians should be
      aware of the existence of a mandatory electronic depository that documents all
      malpractice settlements and judgments involving practitioners.

PMID- 16882797
TI  - Methicillin-resistant Staphylococcus aureus colonization and its association with
      infection among infants hospitalized in neonatal intensive care units.
AB  - OBJECTIVES: We conducted this study to assess the rate of methicillin-resistant
      Staphylococcus aureus colonization and its association with infection among
      infants hospitalized in methicillin-resistant S aureus-endemic NICUs. METHODS:
      Between March 2003 and February 2004, surveillance culture specimens from the
      nares, postauricular areas, axillae, and umbilicus of infants admitted to the
      NICUs at a children's hospital in Taiwan were obtained weekly for the detection
      of methicillin-resistant S aureus. All colonized and clinical isolates from each
      study infant with methicillin-resistant S aureus infection were genotyped with
      pulsed-field gel electrophoresis, with Sma1 digestion, and compared. RESULTS: A
      total of 783 infants were included in this study. Methicillin-resistant S aureus
      colonization was detected for 323 infants during their NICU stays, with detection
      with the first 2 samples for 89%. Nares and umbilicus were the 2 most common
      sites of initial colonization. Methicillin-resistant S aureus colonization was
      associated significantly with premature birth (< or = 28 weeks) and low birth
      weight (< or = 1500 g), and infants with colonization had a significantly higher
      rate of methicillin-resistant S aureus infection, compared with those without
      colonization (26% vs 2%). Methicillin-resistant S aureus colonization was noted
      for 84 of 92 infants with methicillin-resistant S aureus infections. Of the 68
      episodes with previous colonization and isolates available for genotyping
      analysis, colonized and clinical isolates were indistinguishable in 63 episodes,
      highly related in 2 episodes, and distinct in 3 episodes. CONCLUSIONS: More than
      40% of the hospitalized infants were colonized with methicillin-resistant S
      aureus during their stay in methicillin-resistant S aureus-endemic NICUs; this
      was associated significantly with methicillin-resistant S aureus infection. Most
      infants with methicillin-resistant S aureus infections had previous colonization
      with an indistinguishable strain.

PMID- 16882798
TI  - Cerebral palsy among children born after in vitro fertilization: the role of
      preterm delivery--a population-based, cohort study.
AB  - OBJECTIVE: Our aim was to assess the incidence of cerebral palsy among children
      conceived with in vitro fertilization and children conceived without in vitro
      fertilization. METHODS: A population-based, cohort study, including all live-born
      singletons and twins born in Denmark between January 1, 1995, and December 31,
      2000, was performed. Children conceived with in vitro fertilization (9255
      children) were identified through the In Vitro Fertilization Register; children
      conceived without in vitro fertilization (394,713) were identified through the
      Danish Medical Birth Register. Cerebral palsy diagnoses were obtained from the
      National Register of Hospital Discharges. The main outcome measure was the
      incidence of cerebral palsy in the in vitro fertilization and non-in vitro
      fertilization groups. RESULTS: Children born after in vitro fertilization had an
      increased risk of cerebral palsy; these results were largely unchanged after
      adjustment for maternal age, gender, parity, small-for-gestational age status,
      and educational level. The independent effect of in vitro fertilization vanished
      after additional adjustment for multiplicity or preterm delivery. When both
      multiplicity and preterm delivery were included in the multivariate models,
      preterm delivery remained associated strongly with the risk of cerebral palsy.
      CONCLUSIONS: The large proportions of preterm deliveries with in vitro
      fertilization, primarily for twins but also for singletons, pose an increased
      risk of cerebral palsy.

PMID- 16882799
TI  - Incidence of pediatric traumatic brain injury and associated hospital resource
      utilization in the United States.
AB  - OBJECTIVE: The goal was to examine the influence of sociodemographic
      characteristics and health care system factors on the utilization of hospital
      resources by US children < or = 17 years of age with a diagnosis of traumatic
      brain injury. METHODS: A retrospective analysis of data from the Healthcare Cost
      and Utilization Project Kids' Inpatient Database, from January 1, 2000, to
      December 31, 2000, was performed. National estimates of traumatic brain injury
      associated hospitalization rates and resource use were calculated with Kids'
      Inpatient Database sample weighting methods. RESULTS: Of 2,516,833 encounters
      between January 1, 2000, and December 31, 2000, 25,783 cases involved patients <
      or = 17 years of age with a recorded diagnosis of traumatic brain injury. On the
      basis of these data, there were an estimated 50,658 traumatic brain injury
      associated hospitalizations among children < or = 17 years of age in the United
      States in 2000. The traumatic brain injury-associated hospitalization rate was 70
      cases per 100,000 children < or = 17 years of age per year; 15- to 17-year-old
      patients had the highest hospitalization rate (125 cases per 100,000 children per
      year). Pediatric inpatients accrued more than $1 billion in total charges for
      traumatic brain injury-associated hospitalizations in this study. In the
      multivariate regression models, older age, Medicaid insurance status, and
      admission to any type of children's hospital were associated with a longer length
      of stay for pediatric traumatic brain injury-associated hospitalizations. Older
      age, longer length of stay, and in-hospital death predicted higher total charges
      for traumatic brain injury-associated hospitalizations. CONCLUSION: Pediatric
      traumatic brain injury is a substantial contributor to the health resource burden
      in the United States, accounting for more than $1 billion in total hospital
      charges annually.

PMID- 16882800
TI  - Air pollution and infant death in southern California, 1989-2000.
AB  - OBJECTIVE: We evaluated the influence of outdoor air pollution on infant death in
      the South Coast Air Basin of California, an area characterized by some of the
      worst air quality in the United States. METHODS: Linking birth and death
      certificates for infants who died between 1989 and 2000, we identified all infant
      deaths, matched 10 living control subjects to each case subject, and assigned the
      nearest air monitoring station to each birth address. For all subjects, we
      calculated average carbon monoxide, nitrogen dioxide, ozone, and particulate
      matter < 10 microm in aerodynamic diameter exposures experienced during the 2
      week, 1-month, 2-month, and 6-month periods before a case subject's death.
      RESULTS: The risk of respiratory death increased from 20% to 36% per 1-ppm
      increase in average carbon monoxide levels 2 weeks before death in early infancy
      (age: 28 days to 3 months). We also estimated 7% to 12% risk increases for
      respiratory deaths per 10-microg/m3 increase in particulate matter < 10 microm in
      aerodynamic diameter exposure experienced 2 weeks before death for infants 4 to
      12 months of age. Risk of respiratory death more than doubled for infants 7 to 12
      months of age who were exposed to high average levels of particulates in the
      previous 6 months. Furthermore, the risk of dying as a result of sudden infant
      death syndrome increased 15% to 19% per 1-part per hundred million increase in
      average nitrogen dioxide levels 2 months before death. Low birth weight and
      preterm infants seemed to be more susceptible to air pollution-related death
      resulting from these causes; however, we lacked statistical power to confirm this
      heterogeneity with formal testing. CONCLUSIONS: Our results add to the growing
      body of literature implicating air pollution in infant death from respiratory
      causes and sudden infant death syndrome and provide additional information for
      future risk assessment.

PMID- 16882801
TI  - Concepts of the advantages and disadvantages of teenage childbearing among
      pregnant adolescents: a qualitative analysis.
AB  - OBJECTIVE: We sought to enhance our understanding of pregnant adolescents'
      concepts of the advantages and disadvantages of teen pregnancy and childbearing.
      METHODOLOGY: This is a qualitative study of 247 pregnant adolescents recruited
      during their first prenatal health care visit to a women's primary care clinic in
      Providence, Rhode Island. Participants responded in writing to open-ended
      questions assessing their ideas about what was advantageous and disadvantageous
      about having an infant during their teen years rather than waiting until they
      were older. Themes and patterns in responding were coded, and subgroup
      differences based on age, ethnicity, intendedness of current pregnancy, and
      pregnancy/parenting history were assessed. RESULTS: Themes related to advantages
      of teen pregnancy included enhancing connections, positive changes/benefits, and
      practical considerations. Themes related to disadvantages included lack of
      preparedness, changes/interference, and others' perceptions. Differences among
      groups based on age, ethnicity, intendedness of the current pregnancy, and
      pregnancy/parenting history were examined and noted. CONCLUSIONS: Pregnant
      adolescents do not represent a homogeneous group. Considering differences in how
      pregnancy and childbearing are conceptualized along developmental, cultural,
      attitudinal, and experiential lines will strengthen our ability to tailor
      pregnancy-prevention messages.

PMID- 16882802
TI  - Factors influencing the composition of the intestinal microbiota in early
      infancy.
AB  - OBJECTIVE: The aim of this study was to examine the contribution of a broad range
      of external influences to the gut microbiotic composition in early infancy.
      METHODS: Fecal samples from 1032 infants at 1 month of age, who were recruited
      from the KOALA Birth Cohort Study in the Netherlands, were subjected to
      quantitative real-time polymerase chain reaction assays for the enumeration of
      bifidobacteria, Escherichia coli, Clostridium difficile, Bacteroides fragilis
      group, lactobacilli, and total bacterial counts. Information on potential
      determinants of the gut microbiotic composition was collected with repeated
      questionnaires. The associations between these factors and the selected gut
      bacteria were analyzed with univariate and multivariate analyses. RESULTS:
      Infants born through cesarean section had lower numbers of bifidobacteria and
      Bacteroides, whereas they were more often colonized with C difficile, compared
      with vaginally born infants. Exclusively formula-fed infants were more often
      colonized with E coli, C difficile, Bacteroides, and lactobacilli, compared with
      breastfed infants. Hospitalization and prematurity were associated with higher
      prevalence and counts of C difficile. Antibiotic use by the infant was associated
      with decreased numbers of bifidobacteria and Bacteroides. Infants with older
      siblings had slightly higher numbers of bifidobacteria, compared with infants
      without siblings. CONCLUSIONS: The most important determinants of the gut
      microbiotic composition in infants were the mode of delivery, type of infant
      feeding, gestational age, infant hospitalization, and antibiotic use by the
      infant. Term infants who were born vaginally at home and were breastfed
      exclusively seemed to have the most "beneficial" gut microbiota (highest numbers
      of bifidobacteria and lowest numbers of C difficile and E coli).

PMID- 16882803
TI  - Comparison of respiratory physiologic features when infants are placed in car
      safety seats or car beds.
AB  - OBJECTIVE: The objective of this study was to compare the respiratory physiologic
      features of healthy term infants placed in either a car bed or a car safety seat.
      METHODS: Within the first 1 week of life, 67 healthy term infants were recruited
      and assigned randomly to be monitored in either a car bed (33 infants) or a car
      safety seat (34 infants). Physiologic data, including oxygen saturation and
      frequency and type of apnea, were obtained and analyzed in a blinded manner.
      RESULTS: The groups spent similar amounts of time in the devices (car bed: 71.6
      minutes; car seat: 74.2 minutes). The mean oxygen saturation values were not
      different between the groups (car bed: 97.1%; car seat: 97.3%). The percentages
      of time with oxygen saturation of < 95% were also similar for the 2 groups (car
      bed: 11.8[corrected]%; car seat: 18.3[corrected]%). In both groups, a number of
      infants spent high percentages of study time with oxygen saturation of < 95%. The
      6 infants with the most time at this level were all in the car safety seat group
      (54%-63% of study time). Values for the 6 infants in the car bed group with the
      most time at this level were lower (20%-42%). This difference in the duration of
      oxygen saturation of < 95% was not statistically significant. The mean end-tidal
      carbon dioxide levels and the numbers of episodes of apnea were similar for the 2
      groups. CONCLUSIONS: The respiratory physiologic features of infants in the 2 car
      safety devices were observed to be similar. Of note, substantial periods of time
      with oxygen saturation of < 95% were surprisingly common in both groups.

PMID- 16882804
TI  - A randomized, prospective, comparison study of polyethylene glycol 3350 without
      electrolytes and milk of magnesia for children with constipation and fecal
      incontinence.
AB  - OBJECTIVE: Our aim was to compare 2 laxatives, namely, polyethylene glycol 3350
      without electrolytes and milk of magnesia, evaluating the efficacy, safety,
      acceptance, and 1-year outcomes. METHODS: Seventy-nine children with chronic
      constipation and fecal incontinence were assigned randomly to receive
      polyethylene glycol or milk of magnesia and were treated for 12 months in
      tertiary care pediatric clinics. Children were counted as improved or recovered
      depending on resolution of constipation, fecal incontinence, and abdominal pain
      after 1, 3, 6, and 12 months. An intent-to-treat analysis was used. Safety was
      assessed with evaluation of clinical adverse effects and blood tests. RESULTS:
      Thirty-nine children were assigned randomly to receive polyethylene glycol and 40
      to receive milk of magnesia. At each follow-up visit, significant improvement was
      seen in both groups, with significant increases in the frequency of bowel
      movements, decreases in the frequency of incontinence episodes, and resolution of
      abdominal pain. Compliance rates were 95% for polyethylene glycol and 65% for
      milk of magnesia. After 12 months, 62% of polyethylene glycol-treated children
      and 43% of milk of magnesia-treated children exhibited improvement, and 33% of
      polyethylene glycol-treated children and 23% of milk of magnesia-treated children
      had recovered. Polyethylene glycol and milk of magnesia did not cause clinically
      significant side effects or blood abnormalities, except that 1 child was allergic
      to polyethylene glycol. CONCLUSIONS: In this randomized study, polyethylene
      glycol and milk of magnesia were equally effective in the long-term treatment of
      children with constipation and fecal incontinence. Polyethylene glycol was safe
      for the long-term treatment of these children and was better accepted by the
      children than milk of magnesia.

PMID- 16882805
TI  - Natural history of brain lesions in extremely preterm infants studied with serial
      magnetic resonance imaging from birth and neurodevelopmental assessment.
AB  - OBJECTIVES: The aim was to survey the range of cerebral injury and abnormalities
      of cerebral development in infants born between 23 and 30 weeks' gestation using
      serial MRI scans of the brain from birth, and to correlate those findings with
      neurodevelopmental outcome after 18 months corrected age. METHODS: Between
      January 1997 and November 2000, consecutive infants born at < 30 weeks'
      gestational age underwent serial MRI brain scans from birth until term-equivalent
      age. Infants were monitored after 18 months of age, corrected for prematurity,
      with the Griffiths Mental Development Scales and neurologic assessment. RESULTS:
      A total of 327 MRI scans were obtained from 119 surviving infants born at 23 to
      30 weeks of gestation. Four infants had major destructive brain lesions, and
      tissue loss was seen at term for the 2 survivors. Fifty-one infants had early
      hemorrhage; 50% of infants with term scans after intraventricular hemorrhage had
      ventricular dilation. Twenty-six infants had punctate white matter lesions on
      early scans; these persisted for 33% of infants assessed at term. Early scans
      showed cerebellar hemorrhagic lesions for 8 infants and basal ganglia
      abnormalities for 17. At term, 53% of infants without previous hemorrhage had
      ventricular dilation and 80% of infants had diffuse excessive high signal
      intensity within the white matter on T2-weighted scans. Complete follow-up data
      were available for 66% of infants. Adverse outcomes were associated with major
      destructive lesions, diffuse excessive high signal intensity within the white
      matter, cerebellar hemorrhage, and ventricular dilation after intraventricular
      hemorrhage but not with punctate white matter lesions, hemorrhage, or ventricular
      dilation without intraventricular hemorrhage. CONCLUSIONS: Diffuse white matter
      abnormalities and post-hemorrhagic ventricular dilation are common at term and
      seem to correlate with reduced developmental quotients. Early lesions, except for
      cerebellar hemorrhage and major destructive lesions, do not show clear
      relationships with outcomes.

PMID- 16882806
TI  - Differences in the risk associated with head injury for pediatric ice skaters,
      roller skaters, and in-line skaters.
AB  - OBJECTIVE: The goals were to describe the epidemiologic features of pediatric
      skating-related injuries sustained from 1993 to 2003 and to compare ice skating
      related injuries with roller skating--and in-line skating-related injuries.
      METHODS: An analysis of pediatric skating-related injury data from the National
      Electronic Injury Surveillance System of the US Consumer Product Safety
      Commission was performed. RESULTS: An estimated 1 235 467 pediatric skating
      participants presented to hospital emergency departments with injuries between
      1993 and 2003. These children had a mean age of 10.9 years (SD: 3.2 years; range:
      1-18 years), and 50.0% were male. The most common mechanism of injury was a fall
      (83.1%). Ice skaters sustained a greater proportion of head injuries (13.3%),
      compared with roller skaters (4.4%) and in-line skaters (5.0%). Ice skaters also
      experienced a greater proportion of concussions (4.3%), compared with roller
      skaters (0.6%) and in-line skaters (0.8%). The proportion of facial injuries
      among ice skaters was greater than the proportions among roller skaters and in
      line skaters. The majority of roller skating-and in-line skating-related injuries
      were upper-extremity fractures (53.9% and 59.7%, respectively). Children < or = 6
      years of age experienced a greater proportion of head and facial injuries than
      did older children in each skating activity. CONCLUSIONS: The epidemiologic
      features of pediatric ice skating-related injuries differ from those of roller
      skating--and in-line skating-related injuries. Children should wear helmets
      during all recreational skating activities, especially ice skating, because of
      the risk of serious head injuries. Wrist guards should be worn to protect against
      the common upper-extremity fractures sustained during skating.

PMID- 16882807
TI  - Adverse drug reactions among children over a 10-year period.
AB  - OBJECTIVES: This study was designed to evaluate (1) the incidence and common
      types of adverse drug reactions among hospitalized children, (2) the frequency of
      adverse drug reaction reporting by health care providers, and (3) the follow-up
      processes resulting from adverse drug reactions. METHODS: A retrospective cohort
      study of pediatric patients who experienced an adverse drug reaction between
      January 1, 1995, and December 31, 2004, was conducted at a community-based,
      tertiary care, children's teaching hospital. RESULTS: A total of 1087 adverse
      drug reactions were reported; the overall incidence was 1.6%. The severity of
      most adverse drug reactions was low (levels 1-3: 89%; high levels 4-6: 11%).
      Adverse drug reactions with low severity were significantly more common in both
      the general pediatric unit and the NICU. Adverse reactions resulting from use of
      antibiotics (particularly penicillins, cephalosporins, and vancomycin) were
      usually mild. In contrast, adverse drug reactions rated high in severity were
      significantly more common among reactions that led to hospital admission or
      occurred during surgery and among certain drug classes, including anticonvulsants
      and antineoplastic agents. Adverse drug reactions were reported by pharmacists
      (89%), nurses (10%), and physicians (< 1%). Although documentation of physician
      notification occurred for 93% of adverse drug reactions, only 29% of cases were
      documented in the patient's medical chart, 13% included follow-up education for
      individuals involved, and 10% were updated in the allergy profile of the hospital
      computer system. CONCLUSION: Measures to improve detection and reporting of
      adverse drug reactions by all health care professionals should be undertaken, to
      enhance our understanding of the nature and impact of these reactions in
      children.

PMID- 16882808
TI  - Restriction of ongoing intensive care in neonates: a prospective study.
AB  - OBJECTIVE: The purpose of this work was to record the current practice of
      restricting ongoing intensive care in severely ill newborns. METHODS: This was a
      prospective observational study over a 30-month period of consecutive newborns
      for whom restriction of ongoing intensive care was taken into consideration,
      discussed, or decided on. A standardized form recorded patients' medical
      condition, the type of restriction decided on, parents' wishes, and their
      information level. The research was conducted in a neonatal unit of a level III
      university children's hospital, with no interventions. RESULTS: Forty patients
      were enrolled, 25 were preterm, 21 had either a genetic defect or an inborn
      malformation. Restriction of ongoing intensive care was decided on for 32
      patients with a great variety of specified recommendations. Thirty-six patients
      died during the observation period. In general, parents were well informed;
      however, their wishes concerning restriction of ongoing intensive care were
      unknown in approximately 25% of cases. CONCLUSIONS: The decision-making process
      for restriction of ongoing intensive care is well established, but the role of
      parents needs to be defined.

PMID- 16882809
TI  - Risk factors for invasive, early-onset Escherichia coli infections in the era of
      widespread intrapartum antibiotic use.
AB  - OBJECTIVE: The goal was to evaluate risk factors for invasive Escherichia coli
      infections in the first week of life (early onset), focusing on the role of
      intrapartum antibiotic use. METHODS: We conducted a retrospective case-control
      study. Between 1997 and 2001, case infants, defined as infants < 7 days of age
      with E coli isolated from blood or cerebrospinal fluid, were identified in
      selected counties of California, Georgia, and Connecticut by the Active Bacterial
      Core Surveillance/Emerging Infections Program Network. Control infants (N = 1212)
      were identified from a labor and delivery record review of a stratified random
      sample of live births at the same hospitals in 1998 and 1999. RESULTS:
      Surveillance identified 132 E coli cases, including 68 ampicillin-resistant
      cases. The case fatality rate was 16% (21 of 132 cases). Two thirds of case
      infants were preterm, and 49% (64 of 132 infants) were born at < or = 33 weeks of
      gestation. Fifty-three percent of case mothers (70 of 132 mothers) received
      intrapartum antibiotic therapy; 70% of those received ampicillin or penicillin.
      Low gestational age (< or = 33 weeks), intrapartum fever, and membrane rupture of
      > or = 18 hours were associated with increased odds of early-onset E coli
      infection. Results were similar when case subjects were limited to those infected
      with ampicillin-resistant strains. Exposure to any intrapartum antibiotic
      treatment, beta-lactam antibiotic treatment, or > or = 4 hours of intrapartum
      antibiotic therapy was associated with increased odds of E coli infection and
      ampicillin-resistant infection in univariate analyses. Among preterm infants,
      intrapartum antibiotic exposure did not remain associated with either outcome in
      multivariable models. Among term infants, exposure to > or = 4 hours of
      intrapartum antibiotic therapy was associated with decreased odds of early-onset
      E coli infection. CONCLUSIONS: Exposure to intrapartum antibiotic therapy did not
      increase the odds of invasive, early-onset E coli infection. Intrapartum
      antibiotic therapy was effective in preventing E coli infection only among term
      infants.

PMID- 16882810
TI  - Increased rates of morbidity, mortality, and charges for hospitalized children
      with public or no health insurance as compared with children with private
      insurance in Colorado and the United States.
AB  - BACKGROUND: There has been a gradual decrease in the proportion of children
      covered by private health insurance in Colorado and the United States with a
      commensurate increase in those with public insurance or having no insurance which
      may impact access to care and outcomes. OBJECTIVE: The purpose of this work was
      to determine whether children with public or no health insurance have differences
      in hospital admission rates, morbidity, mortality, and/or charges that might be
      improved if standards of primary care comparable to those of children with
      private insurance could be achieved. METHODS: We conducted a retrospective
      comparison of hospitalization-related outcomes for children < 18 years of age in
      Colorado from 1995-2003 and in the United States in 2000. Population-based rates
      for hospital admission were determined stratified by age, race/ethnicity, disease
      grouping, and health insurance status. RESULTS: Compared with those with private
      insurance, children in Colorado and the United States with public or no insurance
      have significantly higher rates of total hospital admission, as well as admission
      for chronic illness, asthma, diabetes, vaccine-preventable disease, psychiatric
      disease, and ruptured appendix. These children have higher mortality rates,
      higher severity of illness, are more likely to be admitted through the emergency
      department and have significantly higher hospital charges per insured child.
      Higher hospitalization rates occur in children who are nonwhite and/or Hispanic
      and those who are younger. If children with public or no health insurance in the
      United States in 2000 had the same hospitalization outcomes as children with
      private insurance, $5.3 billion in hospital charges could have been saved.
      CONCLUSIONS: There is an opportunity to achieve improved health outcomes and
      decreased hospitalization costs for children with public or no health insurance
      if private insurance standards of health care could be achieved for all US
      children.

PMID- 16882811
TI  - Antenatal hydronephrosis as a predictor of postnatal outcome: a meta-analysis.
AB  - OBJECTIVE: Antenatal hydronephrosis is diagnosed in 1% to 5% of all pregnancies;
      however, the antenatal and postnatal management of hydronephrosis varies widely.
      No previous studies define the risk of postnatal pathology in infants with
      antenatal hydronephrosis. Our objective was to review the current literature to
      determine whether the degree of antenatal hydronephrosis and related antenatal
      ultrasound findings are associated with postnatal outcome. METHODS: We searched
      Medline (1966-2005), Embase (1991-2004), and the Cochrane Library databases for
      articles on antenatal hydronephrosis. We required studies to have subjects
      selected on the basis of documented measurements of antenatal hydronephrosis and
      followed to a postnatal diagnosis. We excluded case reports, review articles, and
      editorials. Two independent investigators extracted data. RESULTS: We screened
      1645 citations, of which 17 studies met inclusion criteria. We created a data set
      of 1308 subjects. The risk of any postnatal pathology per degree of antenatal
      hydronephrosis was 11.9% for mild, 45.1% for moderate, and 88.3% for severe.
      There was a significant increase in risk per increasing degree of hydronephrosis.
      The risk of vesicoureteral reflux was similar for all degrees of antenatal
      hydronephrosis. CONCLUSIONS: The findings of this meta-analysis can potentially
      be used for prenatal counseling and may alter current postnatal management of
      children with antenatal hydronephrosis. Overall, children with any degree of
      antenatal hydronephrosis are at greater risk of postnatal pathology as compared
      with the normal population. Moderate and severe antenatal hydronephrosis have a
      significant risk of postnatal pathology, indicating that comprehensive postnatal
      diagnostic management should be performed. Mild antenatal hydronephrosis may
      carry a risk for postnatal pathology, but additional prospective studies are
      needed to determine the optimal management of these children. A well-defined
      prospective analysis is needed to further define the risk of pathology and the
      appropriate management protocols.

PMID- 16882812
TI  - Screening for celiac disease in asymptomatic children with Down syndrome: cost
      effectiveness of preventing lymphoma.
AB  - BACKGROUND: Studies demonstrate an increased prevalence of celiac disease in
      persons with Down syndrome, leading some organizations and authors to recommend
      universal screening of children with Down syndrome. However, many children with
      Down syndrome are asymptomatic, and the long-term implications of screening are
      unknown. The complication of celiac disease that leads to mortality in the
      general population is non-Hodgkin's lymphomas. OBJECTIVES: The purpose of this
      research in asymptomatic children with Down syndrome was to (1) calculate the
      number needed to screen to prevent a single case of lymphoma and (2) present a
      cost-effectiveness study of screening. METHODS: We constructed a decision tree
      using probabilities derived from the published literature for Down syndrome or
      from the general population where Down syndrome-specific data were not available.
      Celiac disease was determined by serologic screening and confirmation with
      intestinal biopsy. Sensitivity analysis was used to alter probability estimates
      affecting the cost of preventing lymphoma. RESULTS: Using our baseline values,
      the no-screen strategy is dominant; that is, screening not only costs more but
      also results in fewer quality-adjusted life-years. A screening strategy costs
      more than $500,000 per life-year gained. Screening all asymptomatic children with
      Down syndrome for celiac disease costs almost $5 million to prevent a single case
      of lymphoma. CONCLUSION: These analyses do not support the cost-effectiveness of
      screening, and more data are needed before recommendations to screen asymptomatic
      children with Down syndrome for celiac disease can be made.

PMID- 16882813
TI  - Vitamin D deficiency in breastfed infants in Iowa.
AB  - OBJECTIVE: The purpose of this work was to assess the vitamin D status of
      breastfed infants living in Iowa (latitude: 41 degrees N). METHODS: Blood samples
      and dietary records from 84 breastfed infants participating in another study were
      used for a survey of vitamin D status at 280 days of age. The vitamin D status of
      those (35 infants) who did not receive preformed vitamin D at 280 days of age
      (unsupplemented infants) was assessed longitudinally between 112 days and 15
      months of age. Plasma 25-hydroxyvitamin D and, in most cases, parathyroid hormone
      and alkaline phosphatase were determined. RESULTS: At 280 days of age, 10% of
      breastfed infants were vitamin D deficient (25-hydroxyvitamin D < 11 ng/mL).
      Deficiency was significantly more prevalent among dark-skinned infants and during
      winter and occurred exclusively in unsupplemented infants. During winter, 78% of
      unsupplemented infants were vitamin D deficient. During summer, only 1 infant who
      had dark skin pigmentation was vitamin D deficient. Longitudinal assessment of
      unsupplemented infants similarly showed that the majority of breastfed infants
      were vitamin D deficient during winter. Severe deficiency (25-hydroxyvitamin D <
      5 ng/mL) was common and was accompanied by elevation of parathyroid hormone and
      alkaline phosphatase. The prevalence of vitamin D deficiency decreased with age
      but was still 12% at 15 months of age if no preformed vitamin D was received.
      CONCLUSIONS: Vitamin D deficiency, including severe deficiency, was common among
      breastfed infants in Iowa who did not receive preformed vitamin D. Deficiency
      occurred mostly during winter but was not completely absent during summer. It
      affected infants with light as well as dark skin pigmentation. Consumption of
      preformed vitamin D from vitamin supplements or formula is effective in
      preventing vitamin D deficiency. Vitamin D supplementation should be provided to
      all breastfed infants.

PMID- 16882814
TI  - Decision analysis in planning for a polio outbreak in the United States.
AB  - OBJECTIVE: Global eradication of poliomyelitis may soon be achieved, but
      circulating polioviruses could reemerge years after eradication by reversion of
      live attenuated oral vaccine virus to a virulent form, laboratory stock
      mishandling, or bioterrorism. If a poliomyelitis outbreak occurs in the United
      States, access to a vaccine stockpile to interrupt viral spread will be
      necessary. Options for the stockpile include the inactivated polio vaccine and
      the live-attenuated trivalent and monovalent oral poliovirus vaccines. With
      differences in immunogenicity, adverse effects, availability, and other issues,
      the optimal vaccine choice for the stockpile is not clear. We sought to compare
      vaccine interventions for poliomyelitis outbreak control. DESIGN: We applied
      decision analysis to 8 strategies for outbreak control: no intervention, 1 or 2
      inactivated polio vaccine doses, 1 or 2 trivalent oral poliovirus vaccine doses,
      1 or 2 monovalent oral poliovirus vaccine doses, and sequential inactivated polio
      vaccine-monovalent oral poliovirus vaccine. Historical data from outbreaks in
      developed countries were used to estimate the risk of paralytic disease after a
      hypothetical reintroduction of circulating polioviruses. The outcome measure was
      cases of paralytic poliomyelitis. RESULTS: Monovalent oral poliovirus vaccine
      provided optimal outbreak control in most scenarios because of high
      seroconversion rates with 1 dose. Control provided by trivalent oral poliovirus
      vaccine and inactivated polio vaccine was equivalent at high vaccine coverage
      rates. At low intervention rates, trivalent oral poliovirus vaccine produced
      fewer paralytic cases than inactivated polio vaccine in highly immune populations
      but more cases than inactivated polio vaccine in poorly immunized groups because
      of secondary transmission of oral poliovirus vaccine virus and vaccine-derived
      viruses. CONCLUSIONS: This model suggests that monovalent oral poliovirus vaccine
      would be the most advantageous vaccine for outbreak control. If a monovalent oral
      poliovirus vaccine stockpile is impractical, the optimal vaccine choice depends
      on the previous immunity and the anticipated intervention rates.

PMID- 16882815
TI  - The influence of variation in type and pattern of symptoms on assessment in
      pediatric asthma.
AB  - OBJECTIVE: We conducted a national, population-based survey to examine the asthma
      related health burden of US children. METHODS: A telephone-based survey was
      conducted in 2004 of children 4 to 18 years of age with current asthma in the
      United States. In 41,433 households screened, 1089 children reported current
      asthma; 801 interviews were completed by parents of children aged 4 to 15 years
      and by children themselves aged 16 to 18 years. The survey included questions
      about symptoms, perceived level of control, activity limitations, health care
      use, medicines, disease management, and knowledge. Global asthma symptom burden,
      derived from the National Asthma Education and Prevention Program guidelines, was
      composed of 3 components: short-term symptom burden (4-week recall), long-term
      symptom burden (past year), and functional impact (activity limitation). RESULTS:
      The majority of children were classified with mild intermittent disease on the
      basis of recent daytime symptoms alone (80%); yet, when report of nighttime
      symptoms was included, the proportion of children classified as having mild
      intermittent symptoms decreased (74%). When asthma burden was assessed on the
      basis of the global symptom burden construct, only a minority (13%) of
      individuals was classified as having an asthma symptom burden consistent with
      mild intermittent disease; the majority (62%) was classified as having
      moderate/severe disease. In addition, the impact of asthma on the daily
      activities is substantial; avoiding exertion (47%) and staying inside (34%) are
      common approaches to improve control of asthma symptoms. CONCLUSIONS: The goals
      of therapy for asthma, based on the National Asthma Education and Prevention
      Program guidelines, have not been achieved for the majority of children. In
      addition, parents and children overestimate the child's asthma control and
      commonly restrict activities to control asthma symptoms. Deficiencies in the
      control of asthma may be related to the underestimation of the burden of disease.

PMID- 16882816
TI  - Comparison of accidental and nonaccidental traumatic head injury in children on
      noncontrast computed tomography.
AB  - OBJECTIVE: Mixed-density convexity subdural hematoma and interhemispheric
      subdural hematoma suggest nonaccidental head injury. The purpose of this
      retrospective observational study is to investigate subdural hematoma on
      noncontrast computed tomography in infants with nonaccidental head injury and to
      compare these findings in infants with accidental head trauma for whom the date
      of injury was known. PATIENTS AND METHODS: Two blinded, independent observers
      retrospectively reviewed computed tomography scans with subdural hematoma
      performed on the day of presentation on 9 infant victims of nonaccidental head
      injury (mean age: 6.8 months; range: 1-25 months) and on 38 infants (mean age:
      4.8 months; range: newborn to 34 months) with accidental head trauma (birth
      related: 19; short fall: 17; motor vehicle accident: 2). RESULTS: Homogeneous
      hyperdense subdural hematoma was significantly more common in children with
      accidental head trauma (28 of 38 [74%]; nonaccidental head trauma: 3 of 9 [33%]),
      whereas mixed-density subdural hematoma was significantly more common in cases of
      nonaccidental head injury (6 of 9 [67%]; accidental head trauma: 7 of 38 [18%]).
      Twenty-two (79%) subdural hematomas were homogeneously hyperdense on noncontrast
      computed tomography performed within two days of accidental head trauma, one (4%)
      was homogeneous and isodense compared to brain tissue, one (4%) was homogeneous
      and hypodense, and four (14%) were mixed-density. There was no statistically
      significant difference in the proportion of interhemispheric subdural hematoma,
      epidural hematoma, calvarial fracture, brain contusion, or subarachnoid
      hemorrhage. CONCLUSIONS: Homogeneous hyperdense subdural hematoma is more
      frequent in cases of accidental head trauma; mixed-density subdural hematoma is
      more frequent in cases of nonaccidental head injury but may be observed within 48
      hours of accidental head trauma. Interhemispheric subdural hematoma is not
      specific for inflicted head injury.

PMID- 16882817
TI  - Prevalence of flat foot in preschool-aged children.
AB  - OBJECTIVES: Our aim with this study was to establish the prevalence of flat foot
      in a population of 3- to 6-year-old children to evaluate cofactors such as age,
      weight, and gender and to estimate the number of unnecessary treatments
      performed. METHODS: A total of 835 children (411 girls and 424 boys) were
      included in this study. The clinical diagnosis of flat foot was based on a valgus
      position of the heel and a poor formation of the arch. Feet of the children were
      scanned (while they were in a standing position) by using a laser surface
      scanner, and rearfoot angle was measured. Rearfoot angle was defined as the angle
      of the upper Achilles tendon and the distal extension of the rearfoot. RESULTS:
      Prevalence of flexible flat foot in the group of 3- to 6-year-old children was
      44%. Prevalence of pathological flat foot was < 1%. Ten percent of the children
      were wearing arch supports. The prevalence of flat foot decreases significantly
      with age: in the group of 3-year-old children 54% showed a flat foot, whereas in
      the group of 6-year-old children only 24% had a flat foot. Average rearfoot angle
      was 5.5 degrees of valgus. Boys had a significant greater tendency for flat foot
      than girls: the prevalence of flat foot in boys was 52% and 36% in girls.
      Thirteen percent of the children were overweight or obese. Significant
      differences in prevalence of flat foot between overweight, obese, and normal
      weight children were observed. CONCLUSIONS: This study is the first to use a
      three-dimensional laser surface scanner to measure the rearfoot valgus in
      preschool-aged children. The data demonstrate that the prevalence of flat foot is
      influenced by 3 factors: age, gender, and weight. In overweight children and in
      boys, a highly significant prevalence of flat foot was observed; in addition, a
      retarded development of the medial arch in the boys was discovered. At the time
      of the study, > 90% of the treatments were unnecessary.

PMID- 16882818
TI  - Long-term height gain of prematurely born children with neonatal growth
      restraint: parallellism with the growth pattern of short children born small for
      gestational age.
AB  - BACKGROUND: It is unknown whether children born very preterm (< 32 weeks'
      gestation) with appropriate size for gestational age, who grow poorly in the
      first postnatal months (ie, preterm growth restraint), show a similar growth
      pattern as children born small for gestational age. OBJECTIVE: Childhood growth
      and adult height of children with preterm growth restraint were compared to those
      of very preterm small-for-gestational-age and non-preterm-growth-restraint
      children. METHODS: Data were drawn from the Project on Preterm and Small-for
      Gestational-Age Infants cohort. Preterm growth restraint was considered to have
      occurred after appropriate-size-for-gestational-age birth and if length and/or
      weight was below -2 SD score at 3 months postterm. RESULTS: Among 380 very
      preterm children, 274 experienced no preterm growth restraint and showed near
      normal growth, whereas 79 (21%) experienced preterm growth restraint and
      subsequently displayed a growth pattern similar to that of very preterm small-for
      gestational-age children (n = 27). Adult height of these children was -1.1 to 
      1.2 SD score. Very preterm small-for-gestational-age and preterm-growth-restraint
      children with a height below -2 SD score at 5 years had an adult height of
      approximately -2.5 SD score. CONCLUSIONS: Childhood growth and adult height were
      similar in very preterm small-for-gestational-age and preterm-growth-restraint
      children. These long-term findings further strengthen the plausibility of
      extending the small-for-gestational-age indication for growth hormone therapy in
      such a way that preterm-growth-restraint children are no longer excluded if they
      have a short stature persisting beyond the age of approximately 5 years.

PMID- 16882819
TI  - High-dose inhaled fluticasone does not replace oral prednisolone in children with
      mild to moderate acute asthma.
AB  - BACKGROUND: Inhaled corticosteroids are not as effective as oral corticosteroids
      in school-aged children with severe acute asthma. It is uncertain how inhaled
      corticosteroids compare with oral corticosteroids in mild to moderate
      exacerbations. PRIMARY OBJECTIVE: The purpose of this work was to determine
      whether there is a significant difference in the percentage of predicted forced
      expiratory volume in 1 second in children with mild to moderate acute asthma
      treated with either inhaled fluticasone or oral prednisolone. METHODS: This was a
      randomized, double-blind controlled trial conducted between 2001 and 2004 in a
      tertiary care pediatric emergency department. We studied a convenience sample of
      69 previously healthy children 5 to 17 years of age with acute asthma and forced
      expiratory volume in 1 second at 50% to 79% predicted value; 41 families refused
      participation. Albuterol was given in the emergency department and salmeterol was
      given after discharge to all patients, as well as either 2 mg of fluticasone via
      metered dose inhaler and valved holding chamber in the emergency department plus
      500 microg twice daily via Diskus for 10 doses after discharge (fluticasone
      group, N = 35) or 2 mg/kg of oral prednisolone in the emergency department plus 5
      daily doses of 1 mg/kg of prednisolone after discharge (prednisolone group, N =
      34). We measured a priori defined absolute change in percent predicted forced
      expiratory volume in 1 second from baseline to 4 and 48 hours in the 2 groups.
      RESULTS. At 240 minutes, the forced expiratory volume in 1 second increased by
      19.1% +/- 12.7% in the fluticasone group and 29.8% +/- 15.5% in the prednisolone
      group. At 48 hours, this difference was no longer significant (estimated
      difference: 4.0 +/- 3.4; P = .14). The relapse rates by 48 hours were 12.5% and
      0% in the fluticasone group and prednisolone group, respectively. CONCLUSION:
      Airway obstruction in children with mild to moderate acute asthma in the
      emergency department improves faster on oral than inhaled corticosteroids.

PMID- 16882821
TI  - Individual and combined effects of postpartum depression in mothers and fathers
      on parenting behavior.
AB  - BACKGROUND: Pediatric anticipatory guidance has been associated with parenting
      behaviors that promote positive infant development. Maternal postpartum
      depression is known to negatively affect parenting and may prevent mothers from
      following anticipatory guidance. The effects of postpartum depression in fathers
      on parenting is understudied. OBJECTIVE: Our purpose with this work was to
      examine the effects of maternal and paternal depression on parenting behaviors
      consistent with anticipatory guidance recommendations. METHODS: The 9-month-old
      wave of data from a national study of children and their families, the Early
      Childhood Longitudinal Study, provided data on 5089 2-parent families. Depressive
      symptoms were measured with a short form of the Center for Epidemiologic Studies
      Depression Scale. Interviews with both parents provided data on parent health
      behaviors and parent-infant interactions. Logistic and linear regression models
      were used to estimate the association between depression in each parent and the
      parenting behaviors of interest. These models were adjusted for demographic and
      socioeconomic status indicators. RESULTS: In this national sample, 14% of mothers
      and 10% of fathers exhibited levels of depressive symptoms on the Center for
      Epidemiologic Studies Depression Scale that have been associated with clinical
      diagnoses, confirming other findings of a high prevalence of postpartum maternal
      depression but highlighting that postpartum depression is a significant issue for
      fathers as well. Mothers who were depressed were approximately 1.5 times more
      likely to engage in less healthy feeding and sleep practices with their infant.
      In both mothers and fathers, depressive symptoms were negatively associated with
      positive enrichment activity with the child (reading, singing songs, and telling
      stories). CONCLUSIONS: Postpartum depression is a significant problem in both
      mothers and fathers in the United States. It is associated with undesirable
      parent health behaviors and fewer positive parent-infant interactions.

PMID- 16882820
TI  - Preoperative anxiety, postoperative pain, and behavioral recovery in young
      children undergoing surgery.
AB  - OBJECTIVE: Findings from published studies suggest that the postoperative
      recovery process is more painful, slower, and more complicated in adult patients
      who had high levels of preoperative anxiety. To date, no similar investigation
      has ever been conducted in young children. METHODS: We recruited 241 children
      aged 5 to 12 years scheduled to undergo elective outpatient tonsillectomy and
      adenoidectomy. Before surgery, we assessed child and parental situational anxiety
      and temperament. After surgery, all subjects were admitted to a research unit in
      which postoperative pain and analgesic consumption were assessed every 3 hours.
      After 24 hours in the hospital, children were discharged and followed up at home
      for the next 14 days. Pain management at home was standardized. RESULTS: Parental
      assessment of pain in their child showed that anxious children experienced
      significantly more pain both during the hospital stay and over the first 3 days
      at home. During home recovery, anxious children also consumed, on average,
      significantly more codeine and acetaminophen compared with the children who were
      not anxious. Anxious children also had a higher incidence of emergence delirium
      compared with the children who were not anxious (9.7% vs 1.5%) and had a higher
      incidence of postoperative anxiety and sleep problems. CONCLUSIONS: Preoperative
      anxiety in young children undergoing surgery is associated with a more painful
      postoperative recovery and a higher incidence of sleep and other problems.

PMID- 16882822
TI  - Interventions for adolescent depression in primary care.
AB  - BACKGROUND: Depression in adolescents is underrecognized and undertreated despite
      its poor long-term outcomes, including risk for suicide. Primary care settings
      may be critical venues for the identification of depression, but there is little
      information about the usefulness of primary care interventions. OBJECTIVE: We
      sought to examine the evidence for the treatment of depression in primary care
      settings, focusing on evidence concerning psychosocial, educational, and/or
      supportive intervention strategies. METHODS: Available data on brief psychosocial
      treatments for adolescent depression in primary settings were reviewed. Given the
      paucity of direct studies, we also drew on related literature to summarize
      available evidence whether brief, psychosocial support from a member of the
      primary care team, with or without medication, might improve depression outcomes.
      RESULTS: We identified 37 studies relevant to treating adolescent depression in
      primary care settings. Only 4 studies directly examined the impact of primary
      care-delivered psychosocial interventions for adolescent depression, but they
      suggest that such interventions can be effective. Indirect evidence from other
      psychosocial/behavioral interventions, including anticipatory guidance and
      efforts to enhance treatment adherence, and adult depression studies also show
      benefits of primary care-delivered interventions as well as the impact of
      provider training to enhance psychosocial skills. CONCLUSIONS: There is potential
      for successful treatment of adolescent depression in primary care, in view of
      evidence that brief, psychosocial support, with or without medication, has been
      shown to improve a range of outcomes, including adolescent depression itself.
      Given the great public health problem posed by adolescent depression, the
      likelihood that most depressed adolescents will not receive specialty services,
      and new guidelines for managing adolescent depression in primary care, clinicians
      may usefully consider initiation of supportive interventions in their primary
      care practices.

PMID- 16882823
TI  - Genetic polymorphisms of hemostasis genes and primary outcome of very low birth
      weight infants.
AB  - BACKGROUND: Recent investigations have reported an influence of thrombophilic
      mutations and antithrombotic risk factors with development of intraventricular
      hemorrhage. It was our objective for this study to investigate the impact of
      genetic polymorphisms of hemostasis genes on the primary outcome measures of
      sepsis, bronchopulmonary dysplasia, intraventricular hemorrhage, and
      periventricular leukomalacia in a large cohort of very low birth weight infants.
      METHODS: There were 586 very low birth weight infants enrolled prospectively in a
      multicenter trial between September 2003 and July 2005, and an additional 595
      very low birth weight infants, who had been recruited in a previous prospective
      trial, were studied. DNA samples were taken by buccal swab, and genotypes of
      factor V Leiden mutation, prothrombin G20210A mutation, the factor VII-323
      del/ins polymorphism, and the factor XIII-Val34Leu polymorphisms were determined
      by polymerase chain reaction and restriction enzyme digestion. RESULTS: In
      contrast to data published previously, the frequency of intraventricular
      hemorrhage or periventricular leukomalacia was not significantly influenced by
      any of the genetic variants tested. Carriers of the factor XIII-Val34Leu
      polymorphism, however, had a higher sepsis rate and a longer period of hospital
      care compared with noncarriers. The factor VII-323 del/ins polymorphism was found
      to be a potential protective factor against bronchopulmonary dysplasia.
      CONCLUSIONS: We could not confirm previously reported associations of hemostasis
      gene variants and development of intraventricular hemorrhage in very low birth
      weight infants. To better understand gene-disease associations in very low birth
      weight infants, the prospective development of large-scale cohorts with well
      defined phenotypes and corresponding DNA samples is essential.

PMID- 16882824
TI  - Cerebral palsy in a term population: risk factors and neuroimaging findings.
AB  - OBJECTIVE: The purpose of this work was to study risk factors and neuroimaging
      characteristics of cerebral palsy in term and near-term infants. PATIENTS AND
      METHODS: Among a cohort of 334,339 infants > or = 36 weeks' gestation born at
      Kaiser Permanente Medical Care Program in northern California in 1991-2003, we
      identified infants with cerebral palsy and obtained clinical data from electronic
      and medical charts. Risk factors for cerebral palsy among infants with different
      brain abnormalities were compared using polytomous logistic regression. RESULTS:
      Of 377 infants with cerebral palsy (prevalence: 1.1 per 1000), 273 (72%) received
      a head computed tomography or MRI. Abnormalities included focal arterial
      infarction (22%), brain malformation (14%), and periventricular white matter
      abnormalities (12%). Independent risk factors for cerebral palsy were maternal
      age > 35, black race, and intrauterine growth restriction. Intrauterine growth
      restriction was more strongly associated with periventricular white matter injury
      than with other neuroimaging findings. Nighttime delivery was associated with
      cerebral palsy accompanied by generalized brain atrophy but not with cerebral
      palsy accompanied by other brain lesions. CONCLUSIONS: Cerebral palsy is a
      heterogeneous syndrome with focal arterial infarction and brain malformation
      representing the most common neuroimaging abnormalities in term and near-term
      infants. Risk factors for cerebral palsy differ depending on the type of
      underlying brain abnormality.

PMID- 16882825
TI  - Treatment of vesicoureteral reflux using endoscopic injection of nonanimal
      stabilized hyaluronic acid/dextranomer gel: initial experience in pediatric
      patients by a single surgeon.
AB  - OBJECTIVE: Endoscopic injection of nonanimal stabilized hyaluronic
      acid/dextranomer gel is an increasingly recognized treatment option for
      vesicoureteral reflux. The procedure is minor compared with open surgery and,
      when successful, avoids the need for long-term antibiotic prophylaxis. We present
      data from our first 18 months using nonanimal stabilized hyaluronic
      acid/dextranomer gel to treat children with vesicoureteral reflux. PATIENTS AND
      METHODS: Pediatric patients aged < or = 15 years with uncomplicated primary
      vesicoureteral reflux were recruited for endoscopic treatment with nonanimal
      stabilized hyaluronic acid/dextranomer gel. A follow-up voiding cystourethrogram
      was scheduled at > or = 2 weeks after treatment, and vesicoureteral reflux
      resolution was defined as grade 0. Repeat nonanimal stabilized hyaluronic
      acid/dextranomer gel treatment was offered to patients with persistent
      vesicoureteral reflux. RESULTS: Of 120 patients treated, 6 were lost to follow
      up, and 7 were yet to undergo posttreatment voiding cystourethrogram. The 107
      remaining patients (efficacy population) had a mean age of 4.1 years (range: 0.5
      15.0), and the median reflux grade was 2 (range: 1-5). The mean time to follow-up
      voiding cystourethrogram was 9.7 weeks (range: 2-26). Vesicoureteral reflux was
      resolved in 82.2% of patients and 86.9% of ureters after initial endoscopic
      treatment with nonanimal stabilized hyaluronic acid/dextranomer gel. The overall
      reflux resolution rate for patients increased to 90.7% after a second treatment
      in 14 patients. Two patients reported postoperative flank pain, although this was
      mild and transient in nature. No other adverse events were reported. No patients
      underwent open surgery for vesicoureteral reflux. CONCLUSIONS: Endoscopic
      treatment with nonanimal stabilized hyaluronic acid/dextranomer gel is effective
      in a high proportion of children with vesicoureteral reflux and, in our opinion,
      may be considered as a first-line treatment option.

PMID- 16882826
TI  - Mimics of childhood stroke: characteristics of a prospective cohort.
AB  - BACKGROUND: Little is known about the clinical features and spectrum of diagnoses
      in children with "stroke mimics," those with acute neurologic deficits but
      without cerebrovascular diseases. OBJECTIVES: Our goal was to describe patients
      with stroke mimics and to determine if clinical features predict benign
      diagnoses. METHODS: Our stroke consult team registered a prospective consecutive
      cohort of 143 patients with acute presentations suspicious for cerebrovascular
      disease from November 2003 to November 2004. Cases in which stroke was ruled out
      (stroke mimics) were reviewed for clinical features and diagnostic test results
      and were classified "benign" if there was no structural brain lesion and there
      was an expectation of complete recovery. RESULTS: Of the 143 cases evaluated for
      suspected stroke, 30 (21%) had stroke mimics. Presenting signs included seizure
      (n = 11), headache (n = 9), mental status change (n = 6), focal weakness (n =
      14), and focal sensory change (n = 7). Eleven patients had "benign" diagnoses (3
      migraine, 3 psychogenic diagnoses, 3 musculoskeletal abnormalities, 1 delirium,
      and 1 episodic vital sign changes). Nineteen patients had "not-benign" diagnoses
      (3 reversible posterior leukoencephalopathy syndrome, 3 neonatal seizures, 2
      vascular anomalies, 2 inflammatory disease, 2 intracranial infection, 2 epilepsy,
      2 metabolic stroke, 1 tumor, 1 drug toxicity, and 1 idiopathic intracranial
      hypertension). Except for the presence of seizures, there were no significant
      differences in presentation or risk factors between benign and not-benign cases.
      CONCLUSIONS: Many disorders mimic childhood stroke. History and clinical
      presentation often do not distinguish the one third of patients with benign
      disorders from the two thirds with more serious problems, necessitating timely
      comprehensive investigations, especially brain MRI.

PMID- 16882827
TI  - Glutathione S-transferase M1 and P1 genotype, passive smoking, and peak
      expiratory flow in asthma.
AB  - OBJECTIVES: Our purpose with this work was to assess the contribution of
      glutathione S-transferase gene variants to asthma susceptibility and pulmonary
      function in relation to tobacco smoke exposure in the home. METHODS: Young
      individuals with asthma (age: 3-21 years; n = 504) were recruited through primary
      and secondary care throughout Tayside, Scotland (BREATHE Study). Spirometry was
      obtained on 407 individuals. Binary logistic regression and general linear
      modeling were used to explore phenotypic characteristics by genotype and tobacco
      smoke exposure status in younger children (3-12 years; n = 384) and teenagers and
      young adults (13-21 years; n = 120). RESULTS: Three- to 12-year-olds with asthma,
      null for the GSTM1 gene or homozygous for the GSTP1Val105 allele, were
      overrepresented in the group exposed to environmental tobacco smoke. No
      differences in lung function values could be detected in this group. In contrast,
      13- to 21-year-olds with the GSTM1-null genotype or homozygous for the
      GSTP1Val105 allele from smoking households were more likely to have a
      substantially lower percentage of predicted peak expiratory flow rates than those
      from nonsmoking households (83% vs 98%). CONCLUSIONS: Three- to 12-year-olds who
      are null for GSTM1 or homozygous for the GSTP1Val105 allele are more susceptible
      to asthma associated with environmental tobacco smoke exposure than those with
      more intact glutathione S-transferase status. In the 13- to 21-year-olds, GSTM1
      null status interacts with environmental tobacco smoke exposure to substantially
      reduce peak expiratory flow rate. The environmental tobacco smoke effect in GSTM1
      null children with asthma could be cumulative over time, resulting in detrimental
      effects on peak expiratory flow rate in 13- to 21-year-olds with asthma.

PMID- 16882828
TI  - The association of third-generation cephalosporin use and invasive candidiasis in
      extremely low birth-weight infants.
AB  - OBJECTIVES: Previous studies have shown that incidence of invasive candidiasis
      varies substantially among centers, and previous use of broad-spectrum
      antibiotics is a risk factor for candidiasis in extremely low birth-weight
      infants. Differences in center practices, such as antibiotic strategies and the
      effects of these strategies on center incidence of candidiasis, are not reflected
      in assessments of an individual's risk of candidiasis. We evaluated the
      relationship between empirical antibiotic practices for extremely low birth
      weight infants and center incidence of candidiasis. METHODS: We studied a cohort
      of extremely low birth-weight infants who survived > or = 72 hours and were
      admitted to 1 of 12 tertiary centers between 1998 and 2001. Multivariable
      logistic regression was used to validate previous broad-spectrum antibiotics use
      as a risk factor for subsequent candidiasis in individual infants. We calculated
      correlation coefficients to assess the relationship between center incidence of
      candidiasis with antibiotic practice patterns. RESULTS: There were 3702 infants
      from 12 centers included, and 284 (7.7%) developed invasive candidiasis. Broad
      spectrum antibiotics use was associated with candidiasis for individual infants.
      Center candidiasis incidence ranged from 2.4% to 20.4%. Center incidence of
      candidiasis was correlated with average broad-spectrum antibiotics use per infant
      and average use of broad-spectrum antibiotics with negative cultures per infant.
      CONCLUSIONS: Center incidences of invasive candidiasis differ substantially, and
      antibiotic practice differences are possible contributors to center variation in
      candidiasis risk.

PMID- 16882829
TI  - Assent for treatment: clinician knowledge, attitudes, and practice.
AB  - OBJECTIVES: Our purpose for this work was to explore clinician knowledge,
      attitudes, and practice regarding assent for medical treatment and to compare
      current practice with existing American Academy of Pediatrics guidelines.
      METHODS: One of the investigators administered a questionnaire to clinicians who
      perform procedures on children at an academic tertiary care pediatric hospital to
      assess knowledge of assent for medical treatment and familiarity with the
      American Academy of Pediatrics policy statement on assent and to measure
      clinician attitudes and approaches to consent/assent in pediatrics. RESULTS: Of
      35 clinicians enrolled, 23 (66%) had heard of the term "assent," and 9 (26%) of
      35 were aware of the American Academy of Pediatrics policy statement on assent.
      Twenty five (74%) of 34 thought 1 of the main goals of assent was to educate the
      child. Only 12 (35%) of 34 included the element of seeking the child's agreement
      as a goal of assent. In practice, the element of explaining the proposed
      treatment was "always" included by 26 (74%) of 35. The element of seeking the
      child's agreement was "always" included by 9 (26%) of 35. CONCLUSIONS: The
      clinicians in this study had limited explicit knowledge of the concept of assent
      for medical treatment and were largely unaware of the recommendations from the
      American Academy of Pediatrics. Their attitudes and practice reflected implicit
      acceptance of the importance of including children in discussions about their
      medical care and reluctance to give children decision-making authority. A model
      of medical decision-making for children that includes education but does not
      allow children to share decision-making authority may be more applicable to
      clinical practice than the current American Academy of Pediatrics-supported model
      of assent.

PMID- 16882830
TI  - The adverse effect of negative comments about weight and shape from family and
      siblings on women at high risk for eating disorders.
AB  - OBJECTIVE: Our purpose with this work was to examine the relationship between
      negative comments about weight, shape, and eating and social adjustment, social
      support, self-esteem, and perceived childhood abuse and neglect. METHODS: A
      retrospective study was conducted with 455 college women with high weight and
      shape concerns, who participated in an Internet-based eating disorder prevention
      program. Baseline assessments included: perceived family negative comments about
      weight, shape, and eating; social adjustment; social support; self-esteem; and
      childhood abuse and neglect. Participants identified 1 of 7 figures representing
      their maximum body size before age 18 and parental maximum body size. RESULTS:
      More than 80% of the sample reported some parental or sibling negative comments
      about their weight and shape or eating. Parental and sibling negative comments
      were positively associated with maximum childhood body size, larger reported
      paternal body size, and minority status. On subscales of emotional abuse and
      neglect, most participants scored above the median, and nearly one third scored
      above the 90th percentile. In a multivariate analysis, greater parental negative
      comments were directly related to higher reported emotional abuse and neglect.
      Maximum body size was also related to emotional neglect. Parental negative
      comments were associated with lower reported social support by family and lower
      self-esteem. CONCLUSIONS: In college women with high weight and shape concerns,
      retrospective reports of negative comments about weight, shape, and eating were
      associated with higher scores on subscales of emotional abuse and neglect. This
      study provides additional evidence that family criticism results in long-lasting,
      negative effects.

PMID- 16882831
TI  - Improving safety-restraint use by children in shopping carts: evaluation of a
      store-based safety intervention.
AB  - OBJECTIVE: Approximately 20,700 children who are < 5 years old are treated in US
      hospital emergency departments annually for shopping cart-related injuries. The
      objective of this study was to evaluate the effectiveness of an in-store
      intervention to increase the use of restraints in shopping carts by children who
      are < 5 years old. METHODS. The study intervention consisted of greeters at the
      store entrance who encouraged the use of appropriate shopping cart restraints
      plus the use of a small cash coupon incentive. The study used a preintervention
      and postintervention design with an untreated "control" group. Three stores
      served as intervention stores, and 4 stores served as nonintervention stores.
      Trained study personnel conducted the observations unobtrusively in all 7 stores
      simultaneously, recording the status of children's restraint use in the shopping
      cart as caregivers approached store checkout areas. The main outcome measure of
      the study was the change in the proportion of children who were < 5 years old,
      riding in a shopping cart, and restrained correctly. RESULTS: There were a total
      of 967 observations, 57% of which were in the 4 nonintervention stores and 43% of
      which were in the 3 intervention stores. There were 442 observations on the
      baseline day and 525 on the follow-up day. Interrater reliability was good.
      Overall, among the 761 cases in which a shopping cart was used, 38% of children
      were transported in the shopping cart seat with the restraint off or used
      improperly, and 24% were seated with the restraint used correctly. In the 4
      nonintervention stores, the percentage of children who were in shopping carts and
      restrained correctly increased from 19% at baseline to 31% during the follow-up
      observation period 1 week later. In the 3 intervention stores, the percentage of
      correct restraint use among children in shopping carts went from 15% at baseline
      to 49% after the intervention during the second observation period. The change in
      correct restraint use among children in shopping carts in intervention stores was
      significantly greater than that in nonintervention stores. CONCLUSIONS: A safety
      intervention, consisting of a $2 incentive coupon plus greeters at the store
      entrance who encouraged the use of appropriate shopping cart restraints,
      significantly increased the correct use of restraints among young children who
      rode in shopping carts. The correct use rate increased to 49% in stores with this
      modest intervention. However, half of the young children in shopping carts
      remained unrestrained or restrained incorrectly. Higher rates of correct
      restraint use may occur with a more comprehensive and sustained shopping cart
      safety intervention. Shopping cart designs that seat children close to the floor
      and that do not rely on caregiver behavior change and vigilance for injury
      protection also should be implemented and evaluated as a passive strategy to
      prevent shopping cart-related injuries to young children.

PMID- 16882832
TI  - Metoclopramide for the treatment of gastroesophageal reflux disease in infants: a
      systematic review.
AB  - OBJECTIVES: Metoclopramide is a commonly used drug to treat gastroesophageal
      reflux disease in infants. Given its widespread use and growing concern about
      toxicity in this population, we conducted a systematic review of metoclopramide
      for the treatment of gastroesophageal reflux disease in infants. METHODS: We
      performed a systematic search of PubMed and bibliographies of relevant review
      articles. We included cohort, case-control, and intervention studies of the
      efficacy, effectiveness, or toxicity of metoclopramide therapy for
      gastroesophageal reflux disease in infants. We excluded case reports, case
      series, review articles, and abstracts. RESULTS: Twelve articles met our
      inclusion criteria. Of these, 11 were prospective trials, and 5 were randomized,
      blinded clinical trials. Study size ranged from 6 to 77 patients. Eight studies
      showed patient improvement with metoclopramide in at least 1 measured outcome; 1
      study showed worsening symptoms with metoclopramide. Of the 5 randomized, blinded
      trials, 2 showed no effect of metoclopramide on any outcome, and 2 showed a
      significant placebo effect. Four studies commented on adverse effects of therapy,
      with irritability being the most frequently reported potential adverse effect of
      therapy. Other reported adverse effects included dystonic reactions, drowsiness,
      oculogyric crisis, emesis, and apnea. Among studies, there was marked
      heterogeneity in the patient populations, dosing, and outcomes studied.
      Therefore, a meta-analysis was not performed. We both agreed on a US Preventive
      Service Task Force rating of "poor" for the level of evidence, leading to an
      "inconclusive" recommendation for the safety and efficacy of metoclopramide in
      infants. CONCLUSIONS: The current literature is insufficient to either support or
      oppose the use of metoclopramide for gastroesophageal reflux disease in infants.
      In the future, large blinded randomized clinical trials are needed to determine
      the efficacy and toxicity of metoclopramide in this population.

PMID- 16882833
TI  - Summary of consensus statement on intersex disorders and their management.
      International Intersex Consensus Conference.

PMID- 16882835
TI  - Oxygen for newborn resuscitation: how much is enough?

PMID- 16882836
TI  - Diagnosing gastroesophageal reflux in preterm infants.

PMID- 16882834
TI  - Extremely growth-retarded infants: is there a viability centile?
AB  - BACKGROUND: It is known that extremely premature infants do less well than more
      mature infants, and this fact has led some countries to adopt a "cutoff for
      viability" using birth weight or gestation. Infants affected by intrauterine
      growth retardation are at additional risk of poor outcome. There are few data to
      inform decisions about viability and (dis)continuation of intensive care when
      both extreme prematurity and severe growth retardation are present. OBJECTIVE: We
      focused on (1) premature infants affected by marked intrauterine growth
      retardation to determine if there was a cutoff weight centile below which the
      mortality sharply increased and (2) the short-term outcome of extremely premature
      and growth-retarded infants to determine a cutoff for viability. METHODS: We
      evaluated preterm infants of 22-32 weeks' gestation if they were alive at the
      onset of labor and born to European mothers resident in the Trent (United
      Kingdom) health region between 1994 and 2003. Infants were categorized into 6
      weight centiles, and infants in each category were assessed for survival to
      discharge from the neonatal unit, duration of respiratory support, length of stay
      in the neonatal unit, and the age at death in nonsurvivors. RESULTS: We
      identified a total of 8228 infants who met the study criteria. Of these, 4448
      infants were male, 6194 were from singleton pregnancies, and 2887 were born at <
      or = 28 completed weeks of gestation. Survival to discharge was markedly reduced
      in the infants born at < or = 28 weeks of gestation with a birth weight less than
      the 2nd centile. Stillbirth was inversely related to birth weight centile in
      infants born before 29 weeks of gestation. CONCLUSIONS: The survival for infants
      born at < or = 28 weeks' gestation and having a birth weight in less than the 2nd
      centile is poor, and consideration should be given to modifying their management.

PMID- 16882837
TI  - Is the high rate of preterm birth in the United States linked to previous induced
      abortions?

PMID- 16882838
TI  - Lessons from "Unexpected increased mortality after implementation of a
      commercially sold computerized physician order entry system".

PMID- 16882839
TI  - Preventing pediatric sudden cardiac death: where do we start?

PMID- 16882840
TI  - What's in a name? Physiologic and pathologic jaundice: the conundrum of defining
      normal bilirubin levels in the newborn.

PMID- 16882841
TI  - Medicaid and physician reimbursement.

PMID- 16882842
TI  - Immunization recommendations for children with metabolic disorders: more data
      would help.

PMID- 16882843
TI  - Early genital surgery to remain controversial.

PMID- 16882844
TI  - Screening for celiac disease in asymptomatic children with Down syndrome: cost
      effectiveness of preventing lymphoma.

PMID- 16882845
TI  - Is there a viability centile for extremely growth-retarded infants?

PMID- 16882846
TI  - Risk of vitamin A toxicity from candy-like chewable vitamin supplements for
      children.
AB  - Numerous vitamin supplements are available over-the-counter to the general
      public. Some such supplements are available as candy-like chewable preparations
      to encourage consumption by children. We report 3 cases of overdose of such
      preparations. Each patient had taken an estimated 200,000 to 300,000 IU of
      vitamin A. Their circulating vitamin A (retinol and retinyl palmitate)
      concentrations were monitored over a 6-month period. There were no clinical or
      biochemical complications noted. However, there were marked increases in both
      retinol and retinyl palmitate concentrations above age-related reference ranges.
      In particular, it took 1 to 3 weeks for the serum retinol concentrations to peak
      and many months for them to normalize. Parents should be warned about the dangers
      of excessive vitamin consumption. Clinicians should be aware of the late peak in
      serum retinol concentrations, which may lead to late complications of vitamin A
      overdose.

PMID- 16882847
TI  - Shopping-cart-related injuries to children. Committee on Injury, Violence, and
      Poison Prevention, American Academy of Pediatrics.
AB  - Shopping cart-related injuries to children are common and can result in severe
      injury or even death. Most injuries result from falls from carts or cart tip
      overs, and injuries to the head and neck represent three fourths of cases. The
      current US standard for shopping carts should be revised to include clear and
      effective performance criteria to prevent falls from carts and cart tip-overs.
      Pediatricians have an important role as educators, researchers, and advocates to
      promote the prevention of these injuries.

PMID- 16882848
TI  - Guiding principles for managed care arrangements for the health care of newborns,
      infants, children, adolescents, and young adults. Committee on Child Health
      Financing, American Academy of Pediatrics.
AB  - By including the precepts of primary care and the medical home in the delivery of
      services, managed care can be instrumental in increasing access to a full range
      of health care services and clinicians. If not designed and administered
      carefully, managed care plans result in underutilization of appropriate services
      and reduced quality of care. Therefore, the American Academy of Pediatrics urges
      the use of the key principles outlined in this statement in designing and
      implementing managed care for newborns, infants, children, adolescents, and young
      adults. This policy statement replaces the 2000 policy statement "Guiding
      Principles for Managed Care Arrangements for the Health Care of Infants,
      Children, Adolescents, and Young Adults."

PMID- 16882849
TI  - Financing of pediatric home health care. Committee on Child Health Financing,
      Section on Home Care, American Academy of Pediatrics.
AB  - In certain situations, home health care has been shown to be a cost-effective
      alternative to inpatient hospital care. National health expenditures reveal that
      pediatric home health costs totaled $5.3 billion in 2000. Medicaid is the major
      payer for pediatric home health care (77%), followed by other public sources
      (22%). Private health insurance and families each paid less than 1% of pediatric
      home health expenses. The most important factors affecting access to home health
      care are the inadequate supply of clinicians and ancillary personnel, shortages
      of home health nurses with pediatric expertise, inadequate payment, and
      restrictive insurance and managed care policies. Many children must stay in the
      NICU, PICU, and other pediatric wards and intermediate care areas at a much
      higher cost because of inadequate pediatric home health care services. The main
      financing problem pertaining to Medicaid is low payment to home health agencies
      at rates that are insufficient to provide beneficiaries access to home health
      services. Although home care services may be a covered benefit under private
      health plans, most do not cover private-duty nursing (83%), home health aides
      (45%), or home physical, occupational, or speech therapy (33%) and/or impose
      visit or monetary limits or caps. To advocate for improvements in financing of
      pediatric home health care, the American Academy of Pediatrics has developed
      several recommendations for public policy makers, federal and state Medicaid
      offices, private insurers, managed care plans, Title V officials, and home health
      care professionals. These recommendations will improve licensing, payment,
      coverage, and research related to pediatric home health services.

PMID- 16882850
TI  - Trauma video review: a valuable resource.

PMID- 16882851
TI  - Influenza vaccine for school-aged children.

PMID- 16882852
TI  - Factors associated with lumbar puncture success.

PMID- 16882853
TI  - Cost savings from universal newborn hearing screening.

PMID- 16882854
TI  - A different view on bilirubin binding.

PMID- 16882855
TI  - Neonatal cardiopulmonary arrest in the delivery room.

PMID- 16882856
TI  - Fabuloso: a cleaning product that tastes and smells good enough to drink.

PMID- 16882857
TI  - Watchful waiting for acute otitis media: are parents and physicians ready?

PMID- 16882858
TI  - Neural representations of location outside the hippocampus.
AB  - Place cells of the rat hippocampus are a dominant model system for understanding
      the role of the hippocampus in learning and memory at the level of single-unit
      and neural ensemble responses. A complete understanding of the information
      processing and computations performed by the hippocampus requires detailed
      knowledge about the properties of the representations that are present in
      hippocampal afferents and efferents in order to decipher the transformations that
      occur to these representations in the hippocampal circuitry. Neural recordings in
      behaving rats have revealed a number of brain areas that contain place-related
      firing properties in the parahippocampal regions and in other brain regions that
      are thought to interact with the hippocampus in certain behavioral tasks.
      Although investigators have just begun to scratch the surface in terms of
      understanding these properties, differences in the precise nature of the spatial
      firing between the hippocampus and these other regions promise to reveal
      important clues regarding the exact role of the hippocampus in learning and
      memory and the nature of its interactions with other brain systems to support
      adaptive behavior.

PMID- 16882859
TI  - Aversive memory reactivation engages in the amygdala only some neurotransmitters
      involved in consolidation.
AB  - Consolidation refers to item stabilization in long-term memory. Retrieval renders
      a consolidated memory sensitive, and a "reconsolidation" process has been
      hypothesized to keep the original memory persistent. Some authors could not
      detect this phenomenon. Here we show that retrieved contextual fear memory is
      vulnerable to amnesic treatments and that the amygdala is critically involved.
      Cholinergic and histaminergic systems seem to modulate only consolidation,
      whereas cannabinoids are involved in both consolidation and reactivation. The
      lability of retrieved memory affords opportunities to treat disorders such as
      phobias, post-traumatic stress, or chronic pain, and these results help searching
      for appropriate therapeutic targets.

PMID- 16882860
TI  - Retrieval induces hippocampal-dependent reconsolidation of spatial memory.
AB  - Nonreinforced retrieval can cause extinction and/or reconsolidation, two
      processes that affect subsequent retrieval in opposite ways. Using the Morris
      water maze task we show that, in the rat, repeated nonreinforced expression of
      spatial memory causes extinction, which is unaffected by inhibition of protein
      synthesis within the CA1 region of the dorsal hippocampus. However, if the number
      of nonreinforced retrieval trials is insufficient to induce long-lasting
      extinction, then a hippocampal protein synthesis-dependent reconsolidation
      process recovers the original memory. Inhibition of hippocampal protein synthesis
      after reversal learning sessions impairs retention of the reversed preference and
      blocks persistence of the original one, suggesting that reversal learning
      involves reconsolidation rather than extinction of the original memory. Our
      results suggest the existence of a hippocampal protein synthesis-dependent
      reconsolidation process that operates to recover or update retrieval-weakened
      memories from incomplete extinction.

PMID- 16882861
TI  - Stability of recent and remote contextual fear memory.
AB  - Following initial encoding, memories undergo a prolonged period of
      reorganization. While such reorganization may occur in many different memory
      systems, its purpose is not clear. Previously, we have shown that recall of
      recent contextual fear memories engages the dorsal hippocampus (dHPC). In
      contrast, recall of remote contextual fear memories engages a number of different
      cortical regions, including the anterior cingulate cortex (ACC). To examine
      whether this reorganization leads to greater memory stability, we examined
      reconsolidation of 1 d-old (recent) and 36 d-old (remote) contextual fear memory
      in mice. We infused the protein synthesis inhibitor, anisomycin (ANI), into
      either the dHPC or ACC immediately following retrieval of either a recent or
      remote contextual fear memory. In the dHPC, ANI infusions disrupted subsequent
      expression of recent, but not remote, contextual fear memory. Similar infusions
      into the ACC had no effect on either recent or remote contextual fear memories,
      whereas systemically applied ANI blocked subsequent remote memory expression when
      long re-exposure durations were used. Together, these data suggest that as
      memories mature they become increasingly stable. Furthermore, the dissociation
      between the effects of systemically and centrally administered ANI on remote
      memory suggests that stability is due, in part, to the distributed nature of
      remote contextual fear memories.

PMID- 16882862
TI  - Disconnection analysis of CA3 and DG in mediating encoding but not retrieval in a
      spatial maze learning task.
AB  - The dentate gyrus (DG) subregion of the hippocampus has been shown to be involved
      in encoding but not retrieval in a spatial maze task (modified Hebb-Williams
      maze). The first experiment in this study examined whether a lesion to the CA3
      would contribute to a similar encoding deficit. A DG group was included in order
      to replicate previous results. Relative to controls, animals receiving CA3
      lesions were impaired in encoding, not retrieval, on the modified Hebb-Williams
      maze--similar to a group that received DG lesions. This suggests the possibility
      that CA3 and DG are working together to mediate encoding processes. The second
      experiment in this study was designed to test the interaction between CA3 and DG
      using a disconnection paradigm. Animals with contralateral lesions (CA3 lesioned
      in one hemisphere, DG lesioned in the other hemisphere) showed a significant
      disruption effect on encoding, but not retrieval, when compared with animals with
      ipsilateral lesions (CA3 and DG lesioned in the same hemisphere, leaving the
      other hemisphere intact). This suggests an interaction between CA3 and DG in
      supporting encoding but not retrieval processes in a spatial maze learning task.

PMID- 16882864
TI  - Identification of programmed translational -1 frameshifting sites in the genome
      of Saccharomyces cerevisiae.

PMID- 16882863
TI  - CREB antisense oligodeoxynucleotide administration into the dorsal hippocampal
      CA3 region impairs long- but not short-term spatial memory in mice.
AB  - The transcription factor cAMP response-element binding protein (CREB) has a
      pivotal role in hippocampal synaptic plasticity and hippocampus-dependent long
      term memory. We recently demonstrated that the dorsal hippocampal CA3 region is
      involved in memory consolidation of spatial information tested on a Morris water
      maze in mice. To test whether activation of CREB in the CA3 region is required
      for memory consolidation of spatial information, bilaterally cannulated mice were
      infused 18 h before the beginning of the behavioral training with antisense or
      control sense CREB oligodeoxynucleotides (ODNs) or buffer. Mice were then
      subjected to massed training in a spatial version of the water maze and tested
      for retention 0 or 24 h after the last training session. We showed that CREB
      antisense ODN-infusion in the CA3 region impaired long-term memory when tested 24
      h later but had no effect on spatial acquisition or short-term memory tested
      immediately after behavioral training. These findings provide evidence that the
      regionally restricted activation of CREB in the dorsal hippocampal CA3 region is
      critical for the long-term memory consolidation phase of spatial learning but not
      for short-term memory.

PMID- 16882865
TI  - Immunotoxicogenomics: the potential of genomics technology in the immunotoxicity
      risk assessment process.
AB  - Evaluation of xenobiotic-induced changes in gene expression as a method to
      identify and classify potential toxicants is being pursued by industry and
      regulatory agencies worldwide. A workshop was held at the Research Triangle Park
      campus of the Environmental Protection Agency to discuss the current state-of-the
      science of "immunotoxicogenomics" and to explore the potential role of genomics
      techniques for immunotoxicity testing. The genesis of the workshop was the
      current lack of widely accepted triggering criteria for Tier 1 immunotoxicity
      testing in the context of routine toxicity testing data, the realization that
      traditional screening methods would require an inordinate number of animals and
      are inadequate to handle the number of chemicals that may need to be screened
      (e.g., high production volume compounds) and the absence of an organized effort
      to address the state-of-the-science of toxicogenomics in the identification of
      immunotoxic compounds. The major focus of the meeting was on the theoretical and
      practical utility of genomics techniques to (1) replace or supplement current
      immunotoxicity screening procedures, (2) provide insight into potential modes or
      mechanisms of action, and (3) provide data suitable for immunotoxicity hazard
      identification or risk assessment. The latter goal is of considerable interest to
      a variety of stakeholders as a means to reduce animal use and to decrease the
      cost of conducting and interpreting standard toxicity tests. A number of data
      gaps were identified that included a lack of dose response and kinetic data for
      known immunotoxic compounds and a general lack of data correlating genomic
      alterations to functional changes observed in vivo. Participants concluded that a
      genomics approach to screen chemicals for immunotoxic potential or to generate
      data useful to risk assessors holds promise but that routine use of these methods
      is years in the future. However, recent progress in molecular immunology has made
      mode and mechanism of action studies much more practical. Furthermore, a variety
      of published immunotoxicity studies suggest that microarray analysis is already a
      practical means to explore pathway-level changes that lead to altered immune
      function. To help move the science of immunotoxicogenomics forward, a partnership
      of industry, academia, and government was suggested to address data gaps,
      validation, quality assurance, and protocol development.

PMID- 16882867
TI  - Adefovir dipivoxyl for the treatment of delta-related liver cirrhosis.
AB  - OBJECTIVE: To report a case suggesting the beneficial effect of adefovir
      dipivoxyl in patients with delta-related decompensated liver cirrhosis
      ineffectively treated with lamivudine. CASE SUMMARY: A 55-year-old woman with
      chronic hepatitis B virus (HBV), antihepatitis Be positive, and hepatitis delta
      virus (HDV)-related decompensated liver cirrhosis (Child-Pugh score B9) was
      awaiting liver transplantation. During this time, she was treated with lamivudine
      100 mg/day; however, the drug was stopped after 8 months because it did not
      produce viral clearance or return serum aminotransferase levels to within normal
      limits. The patient was not a candidate for interferon alfa therapy but was
      prescribed adefovir dipivoxyl 10 mg/day. Five months later, serum
      aminotransferase levels had normalized and, after 7 months of treatment with
      adefovir, the patient became negative for serum HBV-DNA and immunoglobulin M
      (IgM) antidelta. At the time of writing (20 mo of therapy), the HBV-DNA and IgM
      antidelta remained negative, whereas hepatitis B surface antigen and circulating
      HDV-RNA were positive. No adverse effects associated with adefovir were reported,
      and the Child-Pugh score (A6) had improved. DISCUSSION: This is the first
      reported case of some beneficial biochemical and serologic effects of adefovir
      dipivoxyl in the treatment of delta cirrhosis. The virologic pattern of the
      patient after adefovir is indicative of poor liver disease activity and
      prospectively enhances liver transplantation outcome, indicating that adefovir
      might also be useful in the phase prior to liver transplantation. CONCLUSIONS:
      Although we have no plausible explanation for our patient's favorable response to
      adefovir treatment, this case contributes to the knowledge regarding treatment of
      this very difficult condition as well as adefovir efficacy. Given the positive
      outcome, this report suggests that adefovir might be beneficial in patients with
      delta-related liver cirrhosis not responsive to previous lamivudine therapy.
      Based on the high tolerability of this therapy, this case encourages clinical
      trials.

PMID- 16882868
TI  - Rare case of metformin-induced leukocytoclastic vasculitis.
AB  - OBJECTIVE: To report a case of leukocytoclastic vasculitis (LV) related to
      metformin. CASE SUMMARY: A 33-year-old woman developed palpable purpura on her
      lower limbs after starting self-medication with metformin 850 mg/day for weight
      loss. Drug-induced vasculitis was suspected, metformin was stopped, and the rash
      improved significantly. One month later, the woman again took metformin. Similar
      cutaneous lesions recurred, and skin biopsy showed LV, which was managed by
      discontinuing metformin and applying topical antiseptics. The patient had no
      further episodes of skin rash over a follow-up period of 3 months. DISCUSSION:
      Metformin has widespread use throughout the world. It has a variety of metabolic
      and vascular effects. Our patient developed a rash within a few days of metformin
      administration. Resolution of skin manifestations within several days after
      withdrawal of the drug and their recurrence when the drug was reintroduced were
      consistent with a pathogenic role of metformin. Other known causes of vasculitis
      were excluded in a reasonable way. According to the Naranjo probability scale,
      the vasculitis experienced by our patient was probably due to metformin.
      CONCLUSIONS: Clinicians should be aware of the ability of metformin to induce
      cutaneous LV.

PMID- 16882869
TI  - Evaluation of clinical pharmacy services in a hematology/oncology outpatient
      setting.
AB  - BACKGROUND: The Veterans Affairs North Texas Health Care System in Dallas, TX,
      provides a unique opportunity for clinical pharmacists to work as providers. Even
      though clinical pharmacists are actively involved in patient care, many of their
      efforts remain undocumented, resulting in an underestimation of the importance of
      their services and missed opportunities for improvements and new directions.
      OBJECTIVE: To document and evaluate the services of a hematology/oncology
      clinical pharmacy in the outpatient setting. METHODS: Pendragon Forms 3.2
      software was used to design the documentation template. The template was designed
      to collect diagnoses, supportive care issues, drug-specific interventions, and
      prescriptions written. This template was uploaded to the personal digital
      assistant (PDA) for documentation. Patient-specific information was documented in
      a password-protected PDA. Data collected from November 1, 2002, to October 31,
      2003, were retrospectively analyzed. RESULTS: Clinical pharmacists were involved
      in 423 patient visits for chemotherapy follow-up or disease management. Cancer
      diagnoses included colorectal (n = 99), multiple myeloma (59), non-small cell
      lung (56), chronic lymphocytic leukemia (44), myelodysplastic syndromes (22), and
      chronic myelogenous leukemia (19). During the 423 patient visits, 342 supportive
      care issues were addressed including anemia (34%), pain management (22%),
      constipation/diarrhea (15%), and nausea/vomiting (8%). Major drug-specific
      interventions included drug addition (41%), discontinuation (23%), and adjustment
      (21%). Four hundred forty-five prescriptions were filled, of which 181 were new
      and 150 were refilled. CONCLUSIONS: This is the first study, as of July 25, 2006,
      to document considerable contribution of an outpatient clinical pharmacist in
      direct cancer patient care. Although the disease management and supportive care
      issues addressed here may differ based on institution and patient population, the
      results of our study show that clinical pharmacists have ever-growing roles in
      the management of these patients.

PMID- 16882870
TI  - Pharmacokinetics of mycophenolic acid and its glucuronidated metabolites in
      stable lung transplant recipients.
AB  - BACKGROUND: Mycophenolic acid (MPA) is the active metabolite of mycophenolate
      mofetil, an immunosuppressive agent commonly used in solid organ transplantation.
      MPA is metabolized to the inactive metabolite 7-O-mycophenolic acid glucuronide
      (MPAG) and the active metabolite acyl glucuronide (AcMPAG). Pharmacokinetic
      profiling of MPA by determining AUC is a tool for determining drug exposure. Many
      studies, conducted primarily in kidney and some heart and liver transplant
      recipients, have shown wide interpatient variability in MPA's pharmacokinetic
      parameters. There have been few studies in the lung transplant group and, even
      though the lung is not involved in drug elimination, these patients may have
      different MPA pharmacokinetic characteristics. OBJECTIVE: To characterize the
      pharmacokinetic parameters and metabolic ratios of MPA in stable adult lung
      transplant recipients. METHODS: In an open-label manner, lung transplant
      recipients were recruited. Blood samples were obtained at 0, 0.3, 0.6, 1, 1.5, 2,
      4, 6, 8, 10, and 12 hours postdose. Plasma was separated and acidified for drug
      concentration analysis (MPA, MPAG, AcMPAG) by an HPLC-ultraviolet detection
      method. Conventional pharmacokinetic parameters were determined via
      noncompartmental methods. RESULTS: There was large interpatient variability in
      all pharmacokinetic parameters of MPA, MPAG, and AcMPAG. Similar variability was
      observed after stratifying patients into concomitant medication groups:
      cyclosporine and tacrolimus. There was a trend for the tacrolimus group to have a
      higher dose-normalized AUC, higher AUC, lower apparent clearance, and lower AUC
      ratio of AcMPAG/MPA compared with the cyclosporine group. In addition, the
      cyclosporine group had a lower minimum concentration and higher AUC ratio of
      MPAG/MPA than did the tacrolimus group (p < 0.05). CONCLUSIONS: Because of the
      large interpatient variability in the pharmacokinetic parameters of MPA, MPAG,
      and AcMPAG, therapeutic drug monitoring of MPA and its metabolites in lung
      transplant recipients may be beneficial.

PMID- 16882871
TI  - Evaluating the impact of clinical interventions by PharmD students on internal
      medicine clerkships: the results of a 3 year study.
AB  - BACKGROUND: As the practice of pharmacy evolves, requiring more clinically
      oriented healthcare providers, PharmD programs expand their training to more
      hospital sites to expose students to management of a variety of disease states.
      These hospital sites often require proof of the impact of PharmD students on
      patient care over an extended period. This is the first long-term (3 year) study
      reported. OBJECTIVE: To evaluate the impact of clinical interventions by PharmD
      students on internal medicine clerkships over a 3 year period at a 627 bed county
      hospital with 165 general medical/surgical beds and 10 internal medicine teams.
      METHODS: Between January 1, 2003, and December 31, 2005, all pharmacy
      interventions at Kings County Hospital Center in Brooklyn, NY, were recorded and
      analyzed for percentage of contribution, acceptance rate, type, frequency, and
      impact level. RESULTS: PharmD students contributed to 28.8% of all pharmacy
      interventions made, with an acceptance rate for interventions of 92%. The most
      frequent types of interventions performed by PharmD students involved providing
      drug information (46.8%), recommending alternative agents (10.8%), and providing
      drug indications (10.6%). Overall, 49.5% of PharmD student interventions were
      categorized as having moderate to high level impact. CONCLUSIONS: This study
      demonstrates that the impact of PharmD students on clinical interventions is
      significant and improves overall patient care over a long-term period.

PMID- 16882872
TI  - Pharmacotherapy interventions undertaken by pharmacists in the Fleetwood phase
      III study: the role of process control.
AB  - BACKGROUND: The Fleetwood Model incorporates prospective review, direct
      communication with the prescriber, and formalized pharmacotherapy planning in
      patients at highest risk for medication-related problems. OBJECTIVES: To describe
      the intervention activities performed by consultant pharmacists and dispensing
      pharmacists in the context of the Fleetwood Phase III Study. METHODS: We report
      on a total of 4272 residents living in 12 nursing homes included in the
      intervention arm of the demonstration project. The intervention period was
      January through December 2004. Using pharmacotherapy planning software with a Web
      based interface, daily interchange of information from the commercial pharmacy
      software, as well as laptop-based software for use in the nursing homes,
      pharmacists documented the reason for the intervention, the level of service, and
      the extent to which the recommendations were accepted. RESULTS: There were 2118
      Fleetwood interventions performed on 4272 residents (intervention rate: 9.48/100
      resident months), with 81% of interventions performed by consultant pharmacists.
      The top 5 reasons for Fleetwood interventions by dispensing pharmacists were:
      missing information/clarification needed (19.8%), drug-age precautions (14.4%),
      excessive duration alert (9.5%), suboptimal regimen (8.7%), and laboratory test
      needed (7.3%). The top 5 reasons for involvement of the consultant pharmacists
      were: laboratory test needed (13.1%), missing information/clarification needed
      (13%), unnecessary drug (10.3%), product selection opportunity (10.3%), and
      excessive duration alert (9.1%). CONCLUSIONS: Extending the federally mandated
      medication review process in nursing homes to incorporate elements of the
      Fleetwood Model is possible. The recommendation acceptance rates for pharmacist
      interventions are high.

PMID- 16882873
TI  - A man's creation is a living memorial. 1986.

PMID- 16882874
TI  - Role of scavenger receptor MARCO in macrophage responses to CpG
      oligodeoxynucleotides.
AB  - The macrophage Class A scavenger receptor MARCO (macrophage receptor with a
      collagenous structure) functions as a pattern-recognition receptor for bacterial
      components, but its role in responses to CpG oligonucleotide sequences (CpG-ODN)
      in microbial DNA has not been characterized. Phosphorothioate (PS)-linked CpG-ODN
      stimulated IL-12 and NO production in wild-type but not in MARCO-deficient,
      thioglycollate-elicited peritoneal macrophages. MARCO and the related class A
      receptor SR-A belong to a redundant system of receptors for PS ODNs. The ability
      of MARCO to bind CpG-ODNs and conversely, to costimulate IL-12 and NO production
      upon specific ligation with immobilized mAb is consistent with MARCO being a
      signaling receptor for CpG-ODNs, costimulating TLR9-mediated NO and IL-12
      production in macrophages. In contrast to MARCO, SR-A is likely to mediate
      negative regulation of macrophage responses to CpG-ODNs. In particular, increased
      affinity toward SR-A may contribute to decreased potency of oligo G-modified CpG
      ODNs in stimulating IL-12 production. The results suggest that differential
      involvement of activating and inhibitory membrane receptors, such as SR-A and
      MARCO, may underlie profound differences observed in biological activities of
      different ODN sequences.

PMID- 16882875
TI  - Z39Ig is expressed on macrophages and may mediate inflammatory reactions in
      arthritis and atherosclerosis.
AB  - Z39Ig is a transmembrane protein containing two Ig homology domains with unknown
      functions. Immunohistochemical analyses of human carotid atherosclerotic plaques
      detected Z39Ig staining in areas rich in foamy macrophages. Z39Ig staining was
      also observed in macrophages in the lining layers and sublining areas of
      rheumatoid arthritis synovium. Z39Ig staining in the osteoarthritis synovium was
      restricted to macrophages in the lining layers. To identify the role(s) of Z39Ig
      in the function of macrophages, we used human monocytic cell lines TF-1A (Z39Ig
      negative) and THP-1 (Z39Ig-positive). The expression of Z39Ig was induced in TF
      1A cells ,when they were differentiated into macrophages by treatment with PMA.
      The stimulation of PMA-treated TF-1A or THP-1 cells with immobilized anti-Z39Ig
      mAb induced the secretion of IL-8 and matrix metalloproteinase (MMP)-9, which was
      dependent on NF-kappaB activation. These data indicate that the macrophage Z39Ig
      is involved in the pathogenesis of inflammatory diseases through chemokine
      induction, which will promote the migration of inflammatory cells into the lesion
      area, and MMP-9 induction, which will contribute to cartilage destruction or
      extracellular matrix degradation.

PMID- 16882876
TI  - Ligands regulate cell surface level of the human kappa opioid receptor by
      activation-induced down-regulation and pharmacological chaperone-mediated
      enhancement: differential effects of nonpeptide and peptide agonists.
AB  - Two peptide agonists, eight nonpeptide agonists, and five nonpeptide antagonists
      were evaluated for their capacity to regulate FLAG (DYKDDDDK)-tagged human kappa
      opioid receptors (hKORs) stably expressed in Chinese hamster ovary cells after
      incubation for 4 h with a ligand at a concentration approximately 1000-fold of
      its EC(50) (agonist) or K(i) (antagonist) value. Dynorphins A and B decreased the
      fully glycosylated mature form (55-kDa) of FLAG-hKOR by 70%, whereas nonpeptide
      full agonists [2-(3,4-dichlorophenyl)-N-methyl-N-[(2R)-2-pyrrolidin-1
      ylcyclohexyl-]acetamide (U50,488H), 17-cyclopropylmethyl-3,14-dihydroxy-4,5-epoxy
      6-[N-methyl-trans-3-(3-furyl) acrylamido] morphinan hydrochloride (TRK-820),
      ethylketocyclazocine, bremazocine, asimadoline, and (RS)-[3-[1-[[(3,4
      dichlorophenyl)acetyl]-methylamino]-2-(1-pyrrolidinyl)ethyl]phenoxy] acetic acid
      hydrochloride (ICI 204,448) caused 10-30% decreases. In contrast, pentazocine
      (partial agonist) and etorphine (full agonist) up-regulated by approximately 15
      and 25%, respectively. The antagonists naloxone and norbinaltorphimine also
      significantly increased the 55-kDa receptor, whereas selective mu, delta, and
      D(1) receptor antagonists had no effect. Naloxone up-regulated the receptor
      concentration- and time-dependently and enhanced the receptor maturation extent,
      without affecting its turnover. Treatment with brefeldin A (BFA), which disrupts
      Golgi, resulted in generation of a 51-kDa form that resided intracellularly.
      Naloxone up-regulated the new species, indicating that its action site is in the
      endoplasmic reticulum as a pharmacological chaperone. After treatment with BFA,
      all nonpeptide agonists up-regulated the 51-kDa form, whereas dynorphins A and B
      did not, indicating that nonpeptide agonists act as pharmacological chaperones,
      but peptide agonists do not. BFA treatment enhanced down-regulation of the cell
      surface receptor induced by nonpeptide agonists, but not that by peptide
      agonists, and unmasked etorphine- and pentazocine-mediated receptor down
      regulation. These results demonstrate that ligands have dual effects on receptor
      levels: enhancement by chaperone-like effects and agonist-promoted down
      regulation, and the net effect reflects the algebraic sum of the two.

PMID- 16882877
TI  - Busulfan selectively induces cellular senescence but not apoptosis in WI38
      fibroblasts via a p53-independent but extracellular signal-regulated kinase-p38
      mitogen-activated protein kinase-dependent mechanism.
AB  - Busulfan (BU) is a unique alkylating agent that primarily targets slowly
      proliferating or nonproliferating cells in the body, leading to various normal
      tissue damage while killing leukemia cells. However, the mechanism(s) of action
      whereby BU injures normal cells has not been well defined and, therefore, was
      investigated in the present study by using the normal human diploid WI38
      fibroblasts as a model system. We found that WI38 fibroblasts incubated with BU
      (from 7.5-120 microM) for 24 h underwent senescence but not apoptosis in a dose
      independent manner, whereas cells incubated with 80 and 20 microM etoposide
      (Etop) were committed to apoptosis and senescence, respectively. The induction of
      WI38 cell senescence by Etop was associated with p53 activation and could be
      attenuated by down-regulation of p53 using alpha-pifithrin (alpha-PFT) or p53
      small interference RNA (siRNA). In contrast, WI38 cell senescence induced by BU
      was associated with prolonged activation of extracellular signal-regulated kinase
      (Erk), p38 mitogen-activated protein kinase (p38), and c-Jun NH(2)-terminal
      kinase (JNK) and could be suppressed by the inhibition of Erk and/or p38 with
      PD98059 (2'-amino-3'-methoxyflavone) and/or SB203580 [4-(4-fluorophenyl)-2-(4
      methylsulfinylphenyl)-5-(4-pyridyl)1H-imidazole], respectively. However,
      inhibition of p53 with alpha-PFT or p53 siRNA or JNK with SP600125 (1,9
      pyrazoloanthrone) failed to protect WI38 cells from BU-induced senescence. These
      findings suggest that BU is a distinctive chemotherapeutic agent that can
      selectively induce normal human fibroblast senescence through the Erk and p38
      pathways.

PMID- 16882878
TI  - Electron spin resonance and chemiluminescence analyses to elucidate the
      vasodilating mechanism of sodium nitroprusside.
AB  - The aim of this study was to elucidate the vasodilating mechanism of sodium
      nitroprusside (SNP). To do this, SNP was intravenously infused in pigs (1.67
      micromol/kg), and the following paramagnetic metabolites were identified by
      electron spin resonance: 1) nitrosylhemoglobin [HbFe(II)NO] as an index of the
      bioconservative pathway; 2) transferrin; 3) [Fe((II))(CN)(5) NO](3-) and
      [Fe((II))(CN)(4) NO](2-), the reduced penta- and tetracoordinated intermediates
      of SNP, respectively; and 4) methemoglobin (met-Hb). The results indicate the
      following: 1) approximately 17% of the dose is converted to HbFe(II)NO at the end
      of infusion; 2) NO administered as SNP does not undergo bioinactivation
      (oxidative metabolism), because no significant increase of met-Hb was observed;
      3) the equilibrium involving the paramagnetic species of SNP is shifted toward
      HbFe(II)NO, because a significant increase of transferrin but no detection of the
      reduced paramagnetic intermediates of SNP was observed. The results obtained
      indicate that the hemodynamic effect induced by SNP is not mediated by
      HbFe(II)NO, at least under physiological conditions; hence, a direct release of
      NO from SNP in the vascular target should be considered. To demonstrate this
      mechanism, endothelial cells were incubated with SNP, and the release of NO was
      determined by a novel chemiluminescence method. The results indicate that the
      endothelium is able to metabolize SNP, with the formation of stoichiometric
      amounts of NO. In conclusion, SNP is rapidly metabolized to HbFe(II)NO, but the
      pharmacological response is mediated by a direct mechanism of NO release of the
      parent compound at the cellular target.

PMID- 16882879
TI  - Heterogeneity of nicotinic cholinergic receptors in rat superior cervical and
      nodose Ganglia.
AB  - Nicotinic cholinergic receptors (nAChRs) are present in ganglia in the peripheral
      nervous system. In autonomic ganglia, they are responsible for fast synaptic
      transmission, whereas in the sensory ganglia and sensory neurons, they may be
      involved in modulation of neurotransmission. The present study measured nAChRs in
      several rat autonomic ganglia: the superior cervical ganglia (SCG), sensory
      nodose ganglia, stellate ganglia, and pelvic ganglia. The densities of the
      heteromeric nAChRs determined by receptor binding assay in those four ganglia are
      481, 45, 9, and 11 fmol/mg protein, respectively. Immunoprecipitation studies
      with subunit-specific antibodies showed that a majority of the nAChRs in the SCG
      and nodose ganglia contain the alpha3 and beta4 subunits, but a significant
      percentage of the nAChRs in these ganglia also contain alpha5 and beta2 subunits.
      A small percentage of the nAChRs in nodose ganglia also contain alpha2 and alpha4
      subunits. Sequential immunoprecipitation assays indicated that in the SCG, all
      alpha5 subunits are associated with alpha3 and beta4 subunits, forming the mixed
      heteromeric alpha3beta4alpha5 subtype. A receptor composed of alpha3, beta2, and
      beta4 subunits in the SCG was also detected. In rat SCG, we found the following
      distribution of nAChRs subtypes: 55 to 60% simple alpha3beta4 subtype, 25 to 30%
      alpha3beta4alpha5 subtype, and 10 to 15% alpha3beta4beta2 subtype. These findings
      indicate that the nAChRs in SCG and nodose ganglia are heterogeneous, which
      suggests that different receptor subtypes may play different roles in these
      ganglia or may be activated under different conditions.

PMID- 16882880
TI  - Transcriptional activation of CYP2C9, CYP1A1, and CYP1A2 by hepatocyte nuclear
      factor 4alpha requires coactivators peroxisomal proliferator activated receptor
      gamma coactivator 1alpha and steroid receptor coactivator 1.
AB  - Hepatocyte nuclear factor 4alpha (HNF4alpha) is a key transcription factor for
      the constitutive expression of cytochromes P450 (P450s) in the liver. However,
      human hepatoma HepG2 cells show a high level of HNF4alpha but express only
      marginal P450 levels. We found that the HNF4alpha-mediated P450 transcription in
      HepG2 is impaired by the low level of coactivators peroxisomal proliferator
      activated receptor-gamma coactivator 1alpha (PGC1alpha) and steroid receptor
      coactivator 1 (SRC1). Reporter assays with a chimeric CYP2C9-LUC construct
      demonstrated that the sole transfection of coactivators induced luciferase
      activity in HepG2 cells. In HeLa cells however, CYP2C9-LUC activity only
      significantly increased when coactivators were cotransfected with HNF4alpha. A
      deletion mutant lacking the two proximal HNF4alpha binding sites in the CYP2C9
      promoter did not respond to PGC1alpha or SRC1, demonstrating that coactivators
      were acting through HNF4alpha response elements. Adenovirus-mediated transfection
      of PGC1alpha in human hepatoma cells caused a significant dose-dependent increase
      in CYP2C9, CYP1A1, and CYP1A2 and in the positive control CYP7A1. PGC1alpha also
      showed a moderate activating effect on CYP3A4, CYP3A5, and CYP2D6. Adenoviral
      transfection of SRC1 had a lessened effect on P450 genes. Chromatin
      immunoprecipitation assay demonstrated in vivo binding of HNF4alpha and PGC1alpha
      to HNF4alpha response sequences in the CYP2C9 promoter and to three new
      regulatory regions in the common 23.3 kilobase spacer sequence of the CYP1A1/2
      cluster. Insulin treatment of HepG2 and human hepatocytes caused repression of
      PGC1alpha and a concomitant down-regulation of P450s. Our results establish the
      importance of coactivators PGC1alpha and SRC1 for the hepatic expression of human
      P450s and uncover a new HNF4alpha-dependent regulatory mechanism to
      constitutively control the CYP1A1/2 cluster.

PMID- 16882881
TI  - Transcriptional alterations in the left ventricle of three hypertensive rat
      models.
AB  - Left ventricular hypertrophy (LVH) is commonly associated with hypertension and
      represents an independent cardiovascular risk factor. The aim of this study was
      to test the hypothesis that the cardiac overload related to hypertension is
      associated to a specific gene expression pattern independently of genetic
      background. Gene expression levels were obtained with microarrays for 15,866
      transcripts from RNA of left ventricles from 12-wk-old rats of three hypertensive
      models [spontaneously hypertensive rat (SHR), Lyon hypertensive rat (LH), and
      heterozygous TGR(mRen2)27 rat] and their respective controls. More than 60% of
      the detected transcripts displayed significant changes between the three groups
      of normotensive rats, showing large interstrain variability. Expression data were
      analyzed with respect to hypertension, LVH, and chromosomal distribution. Only
      four genes had significantly modified expression in the three hypertensive models
      among which a single gene, coding for sialyltransferase 7A, was consistently
      overexpressed. Correlation analysis between expression data and left ventricular
      mass index (LVMI) over all rats identified a larger set of genes whose expression
      was continuously related with LVMI, including known genes associated with cardiac
      remodeling. Positioning the detected transcripts along the chromosomes pointed
      out high-density regions mostly located within blood pressure and cardiac mass
      quantitative trait loci. Although our study could not detect a unique
      reprogramming of cardiac cells involving specific genes at early stage of LVH, it
      allowed the identification of some genes associated with LVH regardless of
      genetic background. This study thus provides a set of potentially important genes
      contained within restricted chromosomal regions involved in cardiovascular
      diseases.

PMID- 16882882
TI  - Temporal gene expression profiles of target-ablated olfactory epithelium in mice
      with disrupted expression of scavenger receptor A: impact on macrophages.
AB  - Target ablation [removal of the olfactory bulb (OBX)] induces apoptotic death of
      olfactory sensory neurons (OSNs) and an immune response in which activation and
      recruitment of macrophages (ms) into the olfactory epithelium (OE) occupy a
      central role. Ms phagocytose apoptotic neurons and secrete cytokines/growth
      factors that regulate subsequent progenitor cell proliferation and neurogenesis.
      Scavenger receptor A (SR-A) is a pattern recognition receptor that mediates
      binding of ms to apoptotic cells and other relevant immune response functions.
      The aim of this study was to determine the impact of the absence of SR-A on the
      immune response to OBX. The immune response to OBX was evaluated in mice in which
      functional expression of the m scavenger receptor (MSR) was eliminated by gene
      disruption (MSR-/-) and wild-type (wt) mice of the same genetic background. OBX
      induced significant apoptotic death of mature OSNs in the two strains. However,
      subsequent m infiltration and activation and progenitor cell proliferation were
      significantly reduced in MSR-/- vs. wt mice. Gene expression profiling at short
      intervals after OBX demonstrated significant differences in temporal patterns of
      expression of several gene categories, including immune response genes. Many
      immune response genes that showed different temporal patterns of expression are
      related to m function, including cytokine and chemokine secretion, phagocytosis,
      and m maturation and activation. These studies suggest that impairment of the
      immune response to OBX in the OE of MSR-/- mice most likely resulted from
      decreased m adhesion and subsequent reduced infiltration and activation, with a
      resultant decrease in neurogenesis.

PMID- 16882883
TI  - Microarray analysis of Akt1 activation in transgenic mouse hearts reveals
      transcript expression profiles associated with compensatory hypertrophy and
      failure.
AB  - To investigate molecular mechanisms involved in the development of cardiac
      hypertrophy and heart failure, we developed a tetracycline-regulated transgenic
      system to conditionally switch a constitutively active form of the Akt1 protein
      kinase on or off in the adult heart. Short-term activation (2 wk) of Akt1
      resulted in completely reversible hypertrophy with maintained contractility. In
      contrast, chronic Akt1 activation (6 wk) induced extensive cardiac hypertrophy,
      severe contractile dysfunction, and massive interstitial fibrosis. The focus of
      this study was to create a transcript expression profile of the heart as it
      undergoes reversible Akt1-mediated hypertrophy and during the transition from
      compensated hypertrophy to heart failure. Heart tissue was analyzed before
      transgene induction, 2 wk after transgene induction, 2 wk of transgene induction
      followed by 2 days of repression, 6 wk after transgene induction, and 6 wk of
      transgene induction followed by 2 wk of repression. Acute overexpression of Akt1
      (2 wk) leads to changes in the expression of 826 transcripts relative to
      noninduced hearts, whereas chronic induction (6 wk) led to changes in the
      expression of 1,611, of which 65% represented transcripts that were regulated
      during the pathological phase of heart growth. Another set of genes identified
      was uniquely regulated during heart regression but not growth, indicating that
      nonoverlapping transcription programs participate in the processes of cardiac
      hypertrophy and atrophy. These data define the gene regulatory programs
      downstream of Akt that control heart size and contribute to the transition from
      compensatory hypertrophy to heart failure.

PMID- 16882884
TI  - Transcriptome kinetics of arsenic-induced adaptive response in zebrafish liver.
AB  - Arsenic is a prominent environmental toxicant and carcinogen; however, its
      molecular mechanism of toxicity and carcinogenicity remains poorly understood. In
      this study, we performed microarray-based expression profiling on liver of
      zebrafish exposed to 15 parts/million (ppm) arsenic [As(V)] for 8-96 h to
      identify global transcriptional changes and biological networks involved in
      arsenic-induced adaptive responses in vivo. We found that there was an increase
      of transcriptional activity associated with metabolism, especially for
      biosyntheses, membrane transporter activities, cytoplasm, and endoplasmic
      reticulum in the 96 h of arsenic treatment, while transcriptional programs for
      proteins in catabolism, energy derivation, and stress response remained active
      throughout the arsenic treatment. Many differentially expressed genes encoding
      proteins involved in heat shock proteins, DNA damage/repair, antioxidant
      activity, hypoxia induction, iron homeostasis, arsenic metabolism, and ubiquitin
      dependent protein degradation were identified, suggesting strongly that DNA and
      protein damage as a result of arsenic metabolism and oxidative stress caused
      major cellular injury. These findings were comparable with those reported in
      mammalian systems, suggesting that the zebrafish liver coupled with the available
      microarray technology present an excellent in vivo toxicogenomic model for
      investigating arsenic toxicity. We proposed an in vivo, acute arsenic-induced
      adaptive response model of the zebrafish liver illustrating the relevance of many
      transcriptional activities that provide both global and specific information of a
      coordinated adaptive response to arsenic in the liver.

PMID- 16882885
TI  - Questioning INS VNTR role in obesity and diabetes: subclasses tag IGF2-INS-TH
      haplotypes; and -23HphI as a STEP (splicing and translational efficiency
      polymorphism).

PMID- 16882886
TI  - Microarray gene expression analysis in atrophying rainbow trout muscle: a unique
      nonmammalian muscle degradation model.
AB  - Muscle atrophy is a physiological response to diverse physiological and
      pathological conditions that trigger muscle deterioration through specific
      cellular mechanisms. Despite different signals, the biochemical changes in
      atrophying muscle share many common cascades. Muscle deterioration as a
      physiological response to the energetic demands of fish vitellogenesis represents
      a unique model for studying the mechanisms of muscle degradation in non-mammalian
      animals. A salmonid microarray, containing 16,006 cDNAs, was used to study the
      transcriptome response to atrophy of fast-switch muscles from gravid rainbow
      trout compared with sterile fish. Eighty-two unique transcripts were upregulated
      and 120 transcripts were downregulated in atrophying muscles. Transcripts having
      gene ontology identifiers were grouped according to their functions. Muscle
      deterioration was associated with elevated expression of genes involved in the
      catheptic and collagenase proteolytic pathways; the aerobic production,
      buffering, and utilization of ATP; and growth arrest; whereas atrophying muscle
      showed downregulation of genes encoding a serine proteinase inhibitor, enzymes of
      anaerobic respiration, muscle proteins as well as genes required for RNA and
      protein biosynthesis/processing. Therefore, gene transcription of the trout
      muscle atrophy changed in a manner similar to mammalian muscle atrophy. These
      changes result in an arrest of normal cell growth, protein degradation, and
      decreased glycolytic cellular respiration that is characteristic of the fast
      switch muscle. For the first time, other changes/mechanisms unique to fish were
      discussed including genes associated with muscle atrophy.

PMID- 16882887
TI  - Coordinated multitissue transcriptional and plasma metabonomic profiles following
      acute caloric restriction in mice.
AB  - Caloric restriction (CR) increases healthy life span in a range of organisms. The
      underlying mechanisms are not understood but appear to include changes in gene
      expression, protein function, and metabolism. Recent studies demonstrate that
      acute CR alters mortality rates within days in flies. Multitissue transcriptional
      changes and concomitant metabolic responses to acute CR have not been described.
      We generated whole genome RNA transcript profiles in liver, skeletal muscle,
      colon, and hypothalamus and simultaneously measured plasma metabolites using
      proton nuclear magnetic resonance in mice subjected to acute CR. Liver and muscle
      showed increased gene expressions associated with fatty acid metabolism and a
      reduction in those involved in hepatic lipid biosynthesis. Glucogenic amino acids
      increased in plasma, and gene expression for hepatic gluconeogenesis was
      enhanced. Increased expression of genes for hormone-mediated signaling and
      decreased expression of genes involved in protein binding and development
      occurred in hypothalamus. Cell proliferation genes were decreased and cellular
      transport genes increased in colon. Acute CR captured many, but not all, hepatic
      transcriptional changes of long-term CR. Our findings demonstrate a clear
      transcriptional response across multiple tissues during acute CR, with congruent
      plasma metabolite changes. Liver and muscle switched gene expression away from
      energetically expensive biosynthetic processes toward energy conservation and
      utilization processes, including fatty acid metabolism and gluconeogenesis. Both
      muscle and colon switched gene expression away from cellular proliferation. Mice
      undergoing acute CR rapidly adopt many transcriptional and metabolic changes of
      long-term CR, suggesting that the beneficial effects of CR may require only a
      short-term reduction in caloric intake.

PMID- 16882888
TI  - Microarray analysis of gene expression during early stages of mild and severe
      cardiac hypertrophy.
AB  - Familial hypertrophic cardiomyopathy (FHC) is a disease characterized by
      ventricular hypertrophy, fibrosis, and aberrant systolic and/or diastolic
      function. We previously developed two transgenic mouse models that carry FHC
      associated mutations in alpha-tropomyosin (TM): FHC alpha-TM175 mice show patchy
      areas of mild ventricular disorganization and limited hypertrophy, whereas FHC
      alpha-TM180 mice exhibit severe hypertrophy and fibrosis and die within 6 mo. To
      obtain a better understanding of the molecular mechanisms associated with the
      early onset of cardiac hypertrophy, we conducted a detailed comparative analysis
      of gene expression in 2.5-mo-old control, FHC alpha-TM175, and alpha-TM180
      ventricular tissue. Results show that 754 genes (from a total of 22,600) were
      differentially expressed between the nontransgenic (NTG) and the FHC hearts.
      There are 178 differentially regulated genes between NTG and the FHC alpha-TM175
      hearts, 388 genes are differentially expressed between NTG and FHC alpha-TM180
      hearts, and 266 genes are differentially expressed between FHC alpha-TM175 and
      FHC alpha-TM180 hearts. Genes that exhibit the largest increase in expression
      belong to the "secreted/extracellular matrix" category, and those with the most
      significant decrease in expression are associated with "metabolic enzymes."
      Confirmation of the microarray analysis was conducted by quantitative real-time
      PCR on gene transcripts commonly associated with cardiac hypertrophy.

PMID- 16882889
TI  - Surgical treatment compared with eccentric training for patellar tendinopathy
      (Jumper's Knee). A randomized, controlled trial.
AB  - BACKGROUND: Although the surgical treatment of patellar tendinopathy (jumper's
      knee) is a common procedure, there have been no randomized, controlled trials
      comparing this treatment with forms of nonoperative treatment. The purpose of the
      present study was to compare the outcome of open patellar tenotomy with that of
      eccentric strength training in patients with patellar tendinopathy. METHODS:
      Thirty-five patients (forty knees) who had been referred for the treatment of
      grade-IIIB patellar tendinopathy were randomized to surgical treatment (twenty
      knees) or eccentric strength training (twenty knees). The eccentric training
      group performed squats on a 25 degrees decline board as a home exercise program
      (with three sets of fifteen repetitions being performed twice daily) for a twelve
      week intervention period. In the surgical treatment group, the abnormal tissue
      was removed by means of a wedge-shaped full-thickness excision, followed by a
      structured rehabilitation program with gradual progression to eccentric training.
      The primary outcome measure was the VISA (Victorian Institute of Sport
      Assessment) score (possible range, 0 to 100), which was calculated on the basis
      of answers to a symptom-based questionnaire that was developed specifically for
      patellar tendinopathy. The patients were evaluated after three, six, and twelve
      months of follow-up. RESULTS: There was no difference between the groups with
      regard to the VISA score during the twelve-month follow-up period, but both
      groups had improvement (p < 0.001). The mean combined VISA score for the two
      groups increased from 30 (95% confidence interval, 25 to 35) before the start of
      treatment to 49 (95% confidence interval, 42 to 55) at three months, 58 (95%
      confidence interval, 51 to 65) at six months, and 70 (95% confidence interval, 62
      to 78) at twelve months. In the surgical treatment group, five knees had no
      symptoms, twelve had improvement but were still symptomatic, two were unchanged,
      and one was worse after twelve months (p = 0.49 compared with the eccentric
      training group). In the eccentric training group, five knees did not respond to
      treatment and underwent secondary surgery after three to six months. Of the
      remaining fifteen knees in the eccentric training group, seven had no symptoms
      and eight had improvement but were still symptomatic after twelve months.
      CONCLUSIONS: No advantage was demonstrated for surgical treatment compared with
      eccentric strength training. Eccentric training should be tried for twelve weeks
      before open tenotomy is considered for the treatment of patellar tendinopathy.

PMID- 16882890
TI  - The demographic and morphological features of rotator cuff disease. A comparison
      of asymptomatic and symptomatic shoulders.
AB  - BACKGROUND: Very little comparative information is available regarding the
      demographic and morphological characteristics of asymptomatic and symptomatic
      rotator cuff tears. This information is important to provide insight into the
      natural history of rotator cuff disease and to identify which factors may be
      important in the development of pain. The purpose of the present study was to
      compare the morphological characteristics and prevalences of asymptomatic and
      symptomatic rotator cuff disease in patients who presented with unilateral
      shoulder pain. METHODS: Five hundred and eighty-eight consecutive patients in
      whom a standardized ultrasonographic study had been performed by an experienced
      radiologist for the assessment of unilateral shoulder pain were evaluated with
      regard to the presence and size of rotator cuff tears in each shoulder. The
      demographic factors that were analyzed included age, gender, side, and cuff
      thickness. All of these factors were evaluated with regard to their correlation
      with the presence of pain. RESULTS: Of the 588 consecutive patients who met the
      inclusion criteria, 212 had an intact rotator cuff bilaterally, 199 had a
      unilateral rotator cuff tear (either partial or full thickness), and 177 had a
      bilateral tear (either partial or full thickness). The presence of rotator cuff
      disease was highly correlated with age. The average age was 48.7 years for
      patients with no rotator cuff tear, 58.7 years for those with a unilateral tear,
      and 67.8 years for those with a bilateral tear. Logistic regression analysis
      indicated a 50% likelihood of a bilateral tear after the age of sixty-six years
      (p < 0.01). In patients with a bilateral rotator cuff tear in whom one tear was
      symptomatic and the other tear was asymptomatic, the symptomatic tear was
      significantly larger (p < 0.01). The average size of a symptomatic tear was 30%
      greater than that of an asymptomatic tear. Overall, patients who presented with a
      full-thickness symptomatic tear had a 35.5% prevalence of a full-thickness tear
      on the contralateral side. CONCLUSIONS: There is a high correlation between the
      onset of rotator cuff tears (either partial or full thickness) and increasing
      age. Bilateral rotator cuff disease, either symptomatic or asymptomatic, is
      common in patients who present with unilateral symptomatic disease. As the size
      of a tear appears to be an important factor in the development of symptoms, we
      recommend surveillance at yearly intervals for patients with known rotator cuff
      tears that are treated nonoperatively.

PMID- 16882891
TI  - Surgical site infection in the elderly following orthopaedic surgery. Risk
      factors and outcomes.
AB  - BACKGROUND: Risk factor and outcomes data pertaining to surgical site infection
      in the elderly following orthopaedic operations are lacking. The aim of this
      study was to identify risk factors for surgical site infections and to quantify
      the impact of these infections on health outcomes in elderly patients following
      orthopaedic surgery. METHODS: A risk factor and outcomes study was performed at
      Duke University Medical Center, a tertiary care center, and seven community
      hospitals in North Carolina and Virginia between 1991 and 2002. The study
      included elderly patients in whom a surgical site infection had developed
      following orthopaedic surgery and elderly patients in whom a surgical site
      infection had not developed following orthopaedic surgery (controls). Outcome
      measures included mortality during the one-year postoperative period and the
      total length of the hospital stay (including readmissions during the ninety-day
      postoperative period). RESULTS: One hundred and sixty-nine patients with a
      surgical site infection were identified, and 171 controls were selected. The mean
      age of the patients was 74.7 years. The most frequent procedures were hip
      arthroplasty (n = 74, 22%) and open reduction of fractures (n = 55, 16%). The
      most common pathogen was Staphylococcus aureus (n = 95, 56%). A risk factor for
      surgical site infection, identified in the multivariate analysis, was admission
      from a health-care facility (odds ratio = 4.35; 95% confidence interval = 1.64,
      11.11). Multivariate analysis also indicated that surgical site infection was a
      strong predictor of mortality (odds ratio = 3.80; 95% confidence interval = 1.49,
      9.70) and an increased length of stay in the hospital (multiplicative effect =
      2.49; 95% confidence interval = 2.10, 2.94; 9.31 mean attributable days per
      infection, 95% confidence interval = 6.88, 12.13). CONCLUSIONS: Measures for
      prevention of surgical site infection in elderly patients should target
      individuals who reside in health-care facilities prior to surgery. Future studies
      should be done to examine the effectiveness of such interventions in preventing
      infection and improving outcomes in elderly patients who undergo orthopaedic
      surgery.

PMID- 16882892
TI  - Functional outcomes of severe bicondylar tibial plateau fractures treated with
      dual incisions and medial and lateral plates.
AB  - BACKGROUND: Plate fixation of comminuted bicondylar tibial plateau fractures
      remains controversial. This retrospective study was performed to evaluate the
      perioperative results and functional outcomes of medial and lateral plate
      stabilization, through anterolateral and posteromedial surgical approaches, of
      comminuted bicondylar tibial plateau fractures. METHODS: Over a seventy-seven
      month period, eighty-three AO/OTA type-41-C3 bicondylar tibial plateau fractures
      were treated with medial and lateral plate fixation through two exposures. Injury
      radiographs were rank-ordered according to fracture severity. Immediate biplanar
      postoperative radiographs were evaluated to assess the quality of the reduction.
      The Musculoskeletal Function Assessment (MFA) questionnaire was used to evaluate
      functional outcome. RESULTS: Twenty-three male and eighteen female patients
      (average age, forty-six years) who completed the MFA questionnaire were included
      in the study group. The mean duration of follow-up was fifty-nine months. Two
      patients had a deep wound infection. Complete radiographic information was
      available for thirty-one patients. Seventeen (55%) of those patients had a
      satisfactory articular reduction (< or =2-mm step or gap), twenty-eight patients
      (90%) had satisfactory coronal plane alignment (medial proximal tibial angle of
      87 degrees +/- 5 degrees ), twenty-one patients (68%) demonstrated satisfactory
      sagittal plane alignment (posterior proximal tibial angle of 9 degrees +/- 5
      degrees ), and all thirty-one patients demonstrated satisfactory tibial plateau
      width (0 to 5 mm). Patient age and polytrauma were associated with a higher
      (worse) MFA score (p = 0.034 and p = 0.039, respectively). When these variables
      were accounted for, regression analysis demonstrated that a satisfactory
      articular reduction was significantly associated with a better MFA score (p =
      0.029). Rank-order fracture severity was also predictive of MFA outcome (p <
      0.001). No association was identified between rank-order severity and a
      satisfactory articular reduction (p = 0.21). The patients in this series
      demonstrated significant residual dysfunction (p < 0.0001), compared with
      normative data, with the leisure, employment, and movement MFA domains displaying
      the worst scores. CONCLUSIONS: Medial and lateral plate stabilization of
      comminuted bicondylar tibial plateau fractures through medial and lateral
      surgical approaches is a useful treatment method; however, residual dysfunction
      is common. Accurate articular reduction was possible in about half of our
      patients and was associated with better outcomes within the confines of the
      injury severity.

PMID- 16882893
TI  - Nerve root blocks in the treatment of lumbar radicular pain. A minimum five-year
      follow-up.
AB  - BACKGROUND: In a previous prospective, randomized, controlled, double-blinded
      study on the effect of nerve root blocks on the need for operative treatment of
      lumbar radicular pain, we found that injections of corticosteroids were more
      effective than bupivacaine for up to thirteen to twenty-eight months. We
      performed a minimum five-year followup of those patients who had avoided surgery.
      METHODS: All of the patients were considered to be operative candidates by the
      treating surgeon, and all had initially requested operative intervention. They
      had then been randomized to be treated with a selective nerve-root block with
      either bupivacaine or bupivacaine and betamethasone. Both the treating physician
      and the patient were blinded to the type of medication. Of fifty-five randomized
      patients, twenty-nine avoided an operation in the original study. Twenty-one of
      those twenty-nine patients were reevaluated with a follow-up questionnaire at a
      minimum of five years after the initial block. RESULTS: Seventeen of the twenty
      one patients still had not had operative intervention. There was no difference
      between the group treated with bupivacaine alone and the group treated with
      bupivacaine and betamethasone with regard to the avoidance of surgery for five
      years. At the five-year follow-up evaluation, all of the patients who had avoided
      operative treatment had significant decreases in neurological symptoms and back
      pain compared with the baseline values. CONCLUSIONS: The majority of patients
      with lumbar radicular pain who avoid an operation for at least one year after
      receiving a nerve root injection with bupivacaine alone or in combination with
      betamethasone will continue to avoid operative intervention for a minimum of five
      years.

PMID- 16882894
TI  - Correction of moderate and severe acquired flexible flatfoot with medializing
      calcaneal osteotomy and flexor digitorum longus transfer.
AB  - BACKGROUND: Acquired flexible flatfoot encompasses a wide spectrum of disease,
      and there is no validated treatment protocol. We hypothesized that a medializing
      calcaneal osteotomy with a flexor digitorum longus transfer is adequate to
      correct a less severe acquired flexible flatfoot but not a more severe flatfoot.
      We also hypothesized that use of an additional procedure would further correct
      the flatfoot. METHODS: The study included seven pairs of cadaver specimens, with
      one side randomly selected for the creation of a mild flatfoot deformity and the
      other, for the creation of a severe flatfoot deformity. Cyclic axial load was
      applied to the intact foot, to the flatfoot, after correction with a medializing
      calcaneal osteotomy and a flexor digitorum longus transfer, and after the
      addition of a subtalar arthroereisis. Radiographic and pedobarographic data were
      obtained at each stage. A repeated-measures analysis of variance with post hoc
      analysis was used to compare all parameters in the intact foot with those in the
      flatfoot and corrected specimens. A Student t test was used to compare flatfoot
      severity between the mild and severe models. RESULTS: Compared with the intact
      foot, the mild and severe flatfoot models showed a significant change in the
      talar-first metatarsal angle (p = 0.01 and 0.03, respectively), talonavicular
      angle (p = 0.04 and 0.04), and medial cuneiform height (p = 0.03 and 0.05). The
      mild and severe models were significantly different from each other with regard
      to the talar-first metatarsal angle (p = 0.003) and talonavicular angle (p =
      0.002). After the osteotomy and tendon transfer in the mild-flatfoot model, the
      talar-first metatarsal angle and talonavicular angle were not significantly
      different from those in the intact state. In the severe-flatfoot model, the talar
      first metatarsal angle, talonavicular angle, and medial cuneiform height remained
      significantly undercorrected after the osteotomy and tendon transfer. After the
      arthroereisis, the talonavicular angle and medial cuneiform height were not
      significantly different from the values for the intact foot. CONCLUSIONS: In a
      cadaver model, the effectiveness of different procedures on radiographic and
      pedobarographic parameters varies with the severity of an acquired flatfoot
      deformity.

PMID- 16882895
TI  - Treatment of femoro-acetabular impingement with surgical dislocation and
      debridement in young adults.
AB  - BACKGROUND: Femoro-acetabular impingement has been associated with acetabular
      labral and/or articular cartilage damage that may ultimately result in
      osteoarthritis of the hip. Surgical treatment of femoro-acetabular impingement is
      directed at restoring a more normal femoral head-neck offset to alleviate femoral
      abutment against the acetabular rim and treating associated labral and articular
      cartilage damage. METHODS: Thirty hips with femoro-acetabular impingement (in
      twenty-nine patients) underwent debridement through a greater trochanteric flip
      osteotomy and anterior dislocation of the femoral head. There were sixteen male
      patients and thirteen female patients with a mean age of thirty-one years. Cam
      (femoral based) impingement was noted in fourteen hips; pincer (acetabular based)
      impingement, in one hip; and combined cam and pincer impingement, in fifteen
      hips. The mean duration of clinical and radiographic follow-up was thirty-two
      months. All patients were followed according to a prospective protocol, with
      Harris hip scores and plain radiographs obtained preoperatively and at six
      months, one year, and annually for a minimum of two years. RESULTS: The mean
      Harris hip score improved from 70 points preoperatively to 87 points at the time
      of final follow-up (p < 0.0001). Osteonecrosis did not develop in any hip, and
      there were no trochanteric nonunions. In eighteen hips, severe damage of the
      acetabular articular cartilage that had not been appreciated on preoperative
      plain radiographs or magnetic resonance arthrography was noted on arthrotomy.
      Eight of these eighteen hips subsequently had radiographic evidence of
      progression of the osteoarthritis, and four of the eight hips required or were
      expected to soon require conversion to a total hip arthroplasty to treat
      progressive pain. CONCLUSIONS: At the time of early follow-up, we found that
      surgical dislocation and debridement of the hip for the treatment of femoro
      acetabular impingement in hips without substantial damage to the articular
      cartilage can reduce pain and improve function. This procedure has a low rate of
      complications. Radiographic signs of progression of osteoarthritis and clinical
      failure requiring conversion to a total hip arthroplasty were seen only in
      patients with severe damage to the acetabular articular cartilage, a finding that
      emphasizes the need for better imaging methods to assess the extent of damage to
      the acetabular articular cartilage in patients with this disorder.

PMID- 16882896
TI  - Reverse total shoulder arthroplasty. Survivorship analysis of eighty replacements
      followed for five to ten years.
AB  - BACKGROUND: Reverse total shoulder arthroplasty is currently being used to treat
      selected patients with disabling shoulder arthropathy. The purposes of this study
      were to investigate the medium-term results of reverse total shoulder
      arthroplasty and to analyze the influence of etiology on the result. METHODS: We
      carried out a multicenter study with a minimum follow-up of five years and
      determined the survival rate of the prosthesis according to the initial etiology
      of the shoulder arthropathy. Eighty prostheses were implanted in seventy-seven
      patients between 1992 and 1998. Sixty-six shoulders had an arthropathy with a
      massive rotator cuff tear, and fourteen shoulders had a disorder with another
      etiology (rheumatoid arthritis, trauma, or revision arthropathy). At the time of
      review, eighteen patients had died and two were lost to follow-up. The remaining
      fifty-seven patients (sixty shoulders) were examined or interviewed by telephone
      at a mean follow-up of 69.6 months. Cumulative survival curves were generated
      with replacement of the prosthesis, glenoid loosening, and a functional Constant
      score of <30 as the end points. RESULTS: The survival rate with replacement of
      the prosthesis and glenoid loosening as the end points were 91% and 84%,
      respectively, at 120 months, with shoulders that had arthropathy with a massive
      rotator cuff tear demonstrating a significantly better result than those that had
      a disorder with another etiology (p < 0.05). On the other hand, the survival rate
      with an absolute Constant score of <30 as an end point was 58% at 120 months,
      with no significant difference with respect to etiology. Two breaks were observed
      in the survival curves. The first concerned survival until replacement of the
      prosthesis and occurred at around three years, reflecting early loosening of the
      prosthesis. The curve then became stable. A second break started at around six
      years and reflected progressive deterioration of the functional result.
      CONCLUSIONS: Our findings indicate that the reverse total prosthesis should be
      reserved for the treatment of very disabling shoulder arthropathy with a massive
      rotator cuff rupture, and it should be used exclusively in patients over seventy
      years old with low functional demands.

PMID- 16882897
TI  - Computerized navigation for the internal fixation of femoral neck fractures.
AB  - BACKGROUND: Accurate placement of cannulated screws is essential to ensure secure
      fixation of femoral neck fractures. We compared computerized navigation and
      conventional fluoroscopy with regard to the accuracy of screw placement for the
      fixation of femoral neck fractures. METHODS: We retrospectively compared two
      groups of twenty consecutive patients with a femoral neck fracture who underwent
      internal fixation with three cannulated screws. Computer-based navigation was
      used to guide screw placement in one group, and conventional fluoroscopy was used
      in the other group. Radiographic evaluation included the measurement of screw
      parallelism and spread, the calibrated distance from the lesser trochanter, and
      joint penetration. The follow-up period was two years. The rates of complications
      in both groups were evaluated. RESULTS: The navigation-assisted group had better
      screw parallelism and greater spread of the screws. There was a tendency for
      fewer reoperations and significantly fewer overall complications in the patients
      in whom computerized navigation was used (p < 0.018). CONCLUSIONS: Computerized
      navigation improves the accuracy of cannulated screw placement in the internal
      fixation of femoral neck fractures. It may provide better mechanical stability
      and improved fracture outcome.

PMID- 16882898
TI  - Risk factors for recurrence of shoulder instability after arthroscopic Bankart
      repair.
AB  - BACKGROUND: The higher failure rates reported with arthroscopic stabilization of
      traumatic, recurrent anterior shoulder instability compared with open
      stabilization remain a concern. The purpose of this study was to evaluate the
      outcomes of arthroscopic Bankart repairs with the use of suture anchors and to
      identify risk factors related to postoperative recurrence of shoulder
      instability. METHODS: Ninety-one consecutive patients underwent arthroscopic
      stabilization for recurrent anterior traumatic shoulder instability. The mean age
      (and standard deviation) at the time of surgery was 26.4 +/- 5.4 years. Seventy
      one patients were male. Seventy-nine patients were involved in sports (forty, in
      high-risk sports). Capsulolabral reattachment and capsule retensioning was
      performed with use of absorbable suture anchors (mean, 4.3 anchors; range, two to
      seven anchors). All patients were prospectively followed, and, at the time of the
      last review, the patients were examined and assessed functionally by independent
      observers. RESULTS: At a mean follow-up of thirty-six months, fourteen patients
      (15.3%) experienced recurrent instability: six sustained a frank dislocation and
      eight reported a subluxation. The mean delay to recurrence was 17.6 months. The
      risk of postoperative recurrence was significantly related to the presence of a
      bone defect, either on the glenoid side (a glenoid compression-fracture; p =
      0.01) or on the humeral side (a large Hill-Sachs lesion; p = 0.05). By contrast,
      a glenoid separation-fracture was not associated with postoperative recurrent
      dislocation or subluxation. Recurrence of instability was significantly higher in
      patients with inferior shoulder hyperlaxity (p = 0.03) and/or anterior shoulder
      hyperlaxity (p = 0.01). On multivariate analysis, the presence of glenoid bone
      loss and inferior hyperlaxity led to a 75% recurrence rate (p < 0.001). Lastly,
      the number of suture-anchors was critical: patients who had three anchors or
      fewer were at higher risk for recurrent instability (p = 0.03). CONCLUSIONS: In
      the treatment of traumatic recurrent anterior shoulder instability, patients with
      bone loss or with shoulder hyperlaxity are at risk for recurrent instability
      after arthroscopic Bankart repair. At least four anchor points should be used to
      obtain secure shoulder stabilization.

PMID- 16882899
TI  - The contributions of anterior and posterior tibialis dysfunction to varus foot
      deformity in patients with cerebral palsy.
AB  - BACKGROUND: According to traditional teaching, the posterior tibialis is the main
      cause of varus foot deformity in patients with cerebral palsy. However, the
      relative frequency of anterior and posterior tibialis dysfunction has only been
      reported with use of dynamic electromyography in relatively small series of
      patients, with contrasting results. The purpose of the current study was to
      determine the relative prevalence of posterior and anterior tibialis dysfunction
      with use of gait analysis in a large group of patients with cerebral palsy and
      varus foot deformity. METHODS: The muscular contributors to varus foot deformity
      in seventy-eight patients (eighty-eight feet) who had cerebral palsy were
      evaluated with use of computerized motion analysis and dynamic electromyography.
      Data also were examined to identify any relationships between the timing of varus
      during gait and the contributing muscle. RESULTS: The muscular contributor to
      varus deformity was the anterior tibialis in thirty feet, the posterior tibialis
      in twenty-nine feet, both the anterior tibialis and the posterior tibialis in
      twenty-seven feet, and another contributor in two feet. Seventy feet had varus
      deformity during both stance phase and swing phase. Of these seventy feet, twenty
      five exhibited dysfunction of the anterior tibialis, twenty exhibited dysfunction
      of the posterior tibialis, and twenty-three exhibited dysfunction of both
      muscles. Therefore, the timing of varus was not predictive of the contributing
      muscle or muscles. CONCLUSIONS: The current study demonstrated a higher
      prevalence of anterior tibialis dysfunction, both alone and in combination with
      posterior tibialis dysfunction, as a contributor to pes varus in patients with
      pes varus and cerebral palsy than had been reported previously. Dynamic
      electromyography provides clinically useful information for the assessment of
      such patients.

PMID- 16882900
TI  - Lack of effect of a knee ligament injury prevention program on the incidence of
      noncontact anterior cruciate ligament injury.
AB  - BACKGROUND: Studies have suggested that exercise programs can reduce the
      incidence of noncontact injuries of the anterior cruciate ligament in female
      athletes. We conducted a two-year prospective study to assess the effects of a
      knee ligament injury prevention exercise program on the incidence of noncontact
      anterior cruciate ligament injuries in high-school female athletes. METHODS: A
      prospective cohort design was used to study high-school female athletes (playing
      soccer, basketball, and volleyball) from fifteen schools (112 teams) for two
      consecutive seasons. The schools were divided into treatment and control groups.
      The treatment group participated in a plyometric-based exercise program twice a
      week throughout the season. Practice and game exposures and compliance with the
      exercise program were recorded on a weekly basis. Suspected noncontact anterior
      cruciate ligament injuries were confirmed on the basis of the history as well as
      at the time of surgery and/or with magnetic resonance imaging. RESULTS: A total
      of 1439 athletes (862 in the control group and 577 in the treatment group) were
      monitored. There were six confirmed noncontact anterior cruciate ligament
      injuries: three in the treatment group, and three in the control group. The
      incidence of noncontact anterior cruciate ligament injuries per 1000 exposures
      was 0.167 in the treatment group and 0.078 in the control group, yielding an odds
      ratio of 2.05, which was not significant (p > 0.05). CONCLUSIONS: Our results
      suggest that a twenty-minute plyometric-based exercise program that focuses on
      the mechanics of landing from a jump and deceleration when running performed
      twice a week throughout the season will not reduce the rate of noncontact
      anterior cruciate ligament injuries in high-school female athletes.

PMID- 16882901
TI  - Plantar fascia-specific stretching exercise improves outcomes in patients with
      chronic plantar fasciitis. A prospective clinical trial with two-year follow-up.
AB  - BACKGROUND: In a previous investigation, eighty-two patients with chronic
      proximal plantar fasciitis for a duration of more than ten months completed a
      randomized, prospective clinical trial. The patients received instructions for
      either a plantar fascia-stretching protocol or an Achilles tendon-stretching
      protocol and were evaluated after eight weeks. Substantial differences were noted
      in favor of the group managed with the plantar fascia-stretching program. The
      goal of this two-year follow-up study was to evaluate the long-term outcomes of
      the plantar fascia-stretching protocol in patients with chronic plantar
      fasciitis. METHODS: Phase one of the clinical trial concluded at eight weeks. At
      the eight-week follow-up evaluation, all patients were instructed in the plantar
      fascia-stretching protocol. At the two-year follow-up evaluation, a questionnaire
      consisting of the pain subscale of the Foot Function Index and an outcome survey
      related to pain, function, and satisfaction with treatment was mailed to the
      eighty-two subjects who had completed the initial clinical trial. Data were
      analyzed with use of a mixed-model analysis of covariance for each outcome of
      interest. RESULTS: Complete data sets were obtained from sixty-six patients. The
      two-year follow-up results showed marked improvement for all patients after
      implementation of the plantar fascia-stretching exercises, with an especially
      high rate of improvement for those in the original group treated with the
      Achilles tendon-stretching program. In contrast to the eight-week results, the
      two-year results showed no significant differences between the groups with regard
      to the worst pain or pain with first steps in the morning. Descriptive analysis
      of the data showed that 92% (sixty-one) of the sixty-six patients reported total
      satisfaction or satisfaction with minor reservations. Fifty-one patients (77%)
      reported no limitation in recreational activities, and sixty-two (94%) reported a
      decrease in pain. Only sixteen of the sixty-six patients reported the need to
      seek treatment by a clinician. CONCLUSIONS: This study supports the use of the
      tissue-specific plantar fascia-stretching protocol as the key component of
      treatment for chronic plantar fasciitis. Long-term benefits of the stretch
      include a marked decrease in pain and functional limitations and a high rate of
      satisfaction. This approach can provide the health-care practitioner with an
      effective, inexpensive, and straightforward treatment protocol.

PMID- 16882902
TI  - Reliability of a visual analog version of the QuickDASH.
AB  - BACKGROUND: The QuickDASH, an abbreviated form of the Disabilities of the Arm,
      Shoulder and Hand Questionnaire, uses a graded-adjectives ordinal measurement
      response scale. In order to improve the sensitivity of the measure and to make it
      compatible with widely used measures of pain and disability, a visual analog
      scale version was developed. The present study investigated the reliability of
      the new version over time when used for the evaluation of patients undergoing
      treatment. METHODS: A test-retest model with a two-day interval was used to
      evaluate a sample of thirty-eight consecutive patients in an interdisciplinary
      tertiary rehabilitation setting who were identified as having an upper extremity
      disorder. RESULTS: The intraclass correlation coefficient indicating test-retest
      reliability was 0.90 for the eleven-item QuickDASH visual analog scale
      questionnaire (without the work component) and 0.94 for the fifteen-item
      questionnaire (with the work component), neither of which was significantly
      different from the results reported for the original questionnaire. CONCLUSIONS:
      The QuickDASH visual analog scale questionnaire has acceptable reliability over
      time, and it can be used as an alternative to the original QuickDASH.

PMID- 16882903
TI  - Biomechanical studies of double-bundle posterior cruciate ligament
      reconstructions.
AB  - BACKGROUND: Double-bundle reconstruction of the posterior cruciate ligament has
      been advocated to better replicate the anatomy of the native ligament and restore
      normal knee biomechanics. The goal of this study was to measure knee laxities and
      graft forces following single and double-bundle reconstructions and to compare
      these values with those for the intact knee in a cadaver model. METHODS: Forces
      in the posterior cruciate ligament were measured as the knee was passively
      extended from 120 degrees to 0 degrees with applied tibial loading. Anterior
      posterior laxities were measured as well. An anterolateral tunnel was located at
      the anterolateral margin of the native ligament footprint, and a posteromedial
      tunnel was placed at one of two locations within the footprint; one location
      resulted in a wide bridge separating the tunnels and the other, a narrow bridge.
      Testing was repeated with a single anterolateral graft tensioned to match, within
      +/-1 mm, the laxity in the intact knee at 90 degrees of flexion. Double-bundle
      reconstructions were tested with the addition of a posteromedial graft tensioned
      at 30 degrees of flexion. Two levels of posteromedial graft tension (10 and 30 N)
      were studied in both the narrow and the wide-bridge posteromedial tunnels.
      RESULTS: Mean laxities with a single anterolateral graft were 1.1 to 2.0 mm
      greater than normal between 0 degrees and 30 degrees of flexion. With the
      posteromedial graft tensioned to 10 N in the wide-bridge tunnel, the mean laxity
      of the double grafts was not significantly different from that in the intact knee
      at any flexion angle. With the posteromedial graft tensioned to 10 N in the
      narrow-bridge tunnel, the mean laxity at 0 degrees was 0.9 mm greater than that
      in the intact knee. With the posteromedial graft tensioned to 30 N, the mean
      laxity at 10 degrees was 1.7 mm less than the intact-knee value in the wide
      bridge tunnel and 1.3 mm less than the intact-knee value in the narrow bridge
      tunnel. Increasing posteromedial graft tension from 10 to 30 N decreased the mean
      laxities by 0.5 to 1.1 mm between 0 degrees and 30 degrees . Mean graft forces
      following a single anterolateral reconstruction were not significantly different
      from the native posterior cruciate ligament forces under any mode of loading
      except valgus moment. With the wide-bridge tunnel, the mean forces with the
      posteromedial graft tensioned to 10 N were somewhat higher than the native
      posterior cruciate ligament forces at full extension; when the graft was
      tensioned to 30 N, the mean forces were substantially higher. CONCLUSIONS: A
      single anterolateral graft best reproduced the normal posterior cruciate ligament
      force profiles, but laxities were greater than normal between 0 degrees and 30
      degrees of knee flexion. The addition of a second, posteromedial graft reduced
      laxity in this flexion range but did so at the expense of higher-than-normal
      forces in the posteromedial graft.

PMID- 16882904
TI  - Two and three-dimensional computed tomography for the classification and
      management of distal humeral fractures. Evaluation of reliability and diagnostic
      accuracy.
AB  - BACKGROUND: Complex fractures of the distal part of the humerus can be difficult
      to characterize on plain radiographs and two-dimensional computed tomography
      scans. We tested the hypothesis that three-dimensional reconstructions of
      computed tomography scans improve the reliability and accuracy of fracture
      characterization, classification, and treatment decisions. METHODS: Five
      independent observers evaluated thirty consecutive intra-articular fractures of
      the distal part of the humerus for the presence of five fracture characteristics:
      a fracture line in the coronal plane; articular comminution; metaphyseal
      comminution; the presence of separate, entirely articular fragments; and
      impaction of the articular surface. Fractures were also classified according to
      the AO/ASIF Comprehensive Classification of Fractures and the classification
      system of Mehne and Matta. Two rounds of evaluation were performed and then
      compared. Initially, a combination of plain radiographs and two-dimensional
      computed tomography scans (2D) were evaluated, and then, two weeks later, a
      combination of radiographs, two-dimensional computed tomography scans, and three
      dimensional reconstructions of computed tomography scans (3D) were assessed.
      RESULTS: Three-dimensional computed tomography improved both the intraobserver
      and the interobserver reliability of the AO classification system and the Mehne
      and Matta classification system. Three-dimensional computed tomography
      reconstructions also improved the intraobserver agreement for all fracture
      characteristics, from moderate (average kappa [kappa2D] = 0.554) to substantial
      agreement (kappa3D = 0.793). The addition of three-dimensional images had limited
      influence on the interobserver reliability and diagnostic characteristics
      (sensitivity, specificity, and accuracy) for the recognition of specific fracture
      characteristics. Three-dimensional computed tomography images improved
      intraobserver agreement (kappa2D = 0.62 compared with kappa3D = 0.75) but not
      interobserver agreement (kappa2D = 0.24 compared with kappa3D = 0.28) for
      treatment decisions. CONCLUSIONS: Three-dimensional reconstructions improve the
      reliability, but not the accuracy, of fracture classification and
      characterization. The influence of three-dimensional computed tomography was much
      more notable for intraobserver comparisons than for interobserver comparisons,
      suggesting that different observers see different things in the scans-most likely
      a reflection of the training, knowledge, and experience of the observer with
      regard to these relatively uncommon and complex injuries.

PMID- 16882905
TI  - Arthroscopic management of septic arthritis of the shoulder joint.
AB  - BACKGROUND: Nineteen patients with septic arthritis of the glenohumeral joint
      were treated with a combination of arthroscopic irrigation and debridement and
      systemic antibiotics according to bacterial sensitivity. We retrospectively
      reviewed the series to determine the efficacy and safety of this treatment.
      METHODS: There were seventeen men and two women, with a mean age of fifty-nine
      years. Underlying medical disease was present in thirteen patients, with six of
      them having diabetes. The average duration of symptoms prior to the arthroscopic
      lavage was three weeks. Fifteen patients had had local injections into the
      shoulder joint. The arthroscopic staging of the infection was based on the
      modified criteria of Gachter. The functional outcome was evaluated with use of
      the UCLA scoring system. RESULTS: As determined at arthroscopy, one infection was
      classified as stage I; seven, as stage II; nine, as stage III; and two, as stage
      IV. Staphylococcus was the most common organism identified. The infection was
      eradicated completely with a single arthroscopic procedure in fourteen patients.
      The mean UCLA score at the time of the last follow-up was 26 points, with a mean
      score of 23.7 points for the eleven patients with a rotator cuff tear and 29
      points for the eight with an intact rotator cuff. Patients who had had symptoms
      for no more than two weeks prior to the arthroscopic lavage had better results
      than those who had had symptoms for longer than two weeks. CONCLUSIONS:
      Arthroscopic debridement for the treatment of septic arthritis of the shoulder is
      safe and efficient, particularly in the early stages of the disease. Underlying
      medical diseases such as diabetes, prior injections, or a preexisting rotator
      cuff tear were seen in a high proportion of these patients.

PMID- 16882906
TI  - Distribution of A-delta and C-fiber receptors in the cervical facet joint capsule
      and their response to stretch.
AB  - BACKGROUND: It has been proposed that cervical facet joint capsules are a major
      source of whiplash pain. However, there is a paucity of neurophysiologic data to
      support this hypothesis. The purposes of this study were to determine the
      distribution of A-delta and C-fiber sensory receptors in the facet joint capsule
      and to test their patterns of response to stretch and related sensory function.
      METHODS: Laminectomy from C4 to C7 was performed in seventeen goats, while they
      were under general anesthesia, to expose the C6 nerve roots. Customized dual
      bipolar electrodes were used to record neural activity from one of the C6
      branches. An 8 or 15-V electrical stimulus was used to provoke receptor activity
      in nine designated areas on the dorsal part of the C5-C6 facet joint capsule.
      Receptors were classified on the basis of conduction velocities. The waveform of
      an identified receptor was set up as a template to determine its neural activity
      in response to capsular stretch. The characteristics of each single receptor's
      response to capsular stretch were analyzed to determine its sensory function as a
      mechanoreceptor or nociceptor. RESULTS: Two hundred and forty-eight receptors on
      the dorsal part of the C5-C6 facet joint capsule were evoked by electrical
      stimulation in the seventeen goats. More C-fiber receptors were found on the
      dorsolateral aspect of the facet joint capsule, where tendons and muscles were
      attached. The response to stretch of 120 receptors, from twelve goats, were
      analyzed to classify them into one of four categories (high-threshold
      mechanoreceptors, non-saturated low-threshold mechanoreceptors, saturated low
      threshold mechanoreceptors, and silent receptors) or as unclassified receptors.
      CONCLUSIONS: The existence of receptors in the facet joint capsule indicates that
      the capsule has pain and proprioceptive sensory functions.

PMID- 16882907
TI  - Minimum ten-year results of primary bipolar hip arthroplasty for degenerative
      arthritis of the hip.
AB  - BACKGROUND: Bipolar hip arthroplasty has been advocated by some as an alternative
      to total hip arthroplasty for the treatment of degenerative arthritis of the hip.
      We sought to assess the results of this procedure at our institution after a
      minimum duration of follow-up of ten years. METHODS: We retrospectively reviewed
      a consecutive series of 152 patients (173 hips) who underwent primary bipolar
      hemiarthroplasty for the treatment of symptomatic degenerative arthritis of the
      hip with a cementless femoral component between 1983 and 1987. Of the original
      cohort of 152 patients, ninety-two patients (104 hips) were available for
      clinical and radiographic review at a mean of 12.2 years postoperatively. At the
      time of the latest follow-up, self-administered Harris hip questionnaires were
      used to assess pain, mobility, activity level, and overall satisfaction with the
      procedure. Biplanar hip radiographs were made to evaluate bipolar shell
      migration, osteolysis, and femoral stem fixation. RESULTS: At the time of the
      latest follow-up, nineteen patients (nineteen hips) had undergone revision to
      total hip arthroplasty because of mechanical failure, and three patients (three
      hips) were awaiting revision because of symptomatic radiographic mechanical
      failure. Twelve acetabular revisions were performed or scheduled for the
      treatment of pelvic osteolysis or protrusio acetabuli secondary to component
      migration. Acetabular reconstruction required bone-grafting, an oversized shell,
      and/or a pelvic reconstruction ring. The overall rate of mechanical failure was
      21.2% (twenty-two of 104 hips), with 91% (twenty) of the twenty-two failures
      involving the acetabular component. Reaming of the acetabulum at the time of the
      index arthroplasty was associated with a 6.4-fold greater risk of revision. The
      rate of implant survival, with revision because of mechanical failure as the end
      point, was 94.2% for femoral components and 80.8% for acetabular components at a
      mean of 12.2 years. Of the remaining sixty-nine patients (eighty-one hips) in
      whom the original prosthesis was retained, seventeen patients (24.6%) rated the
      pain as moderate to severe. Nearly 30% of patients with an intact prosthesis
      required analgesics on a regular basis. Radiographs were available for fifty
      eight hips (including all of the hips with moderate to severe pain) after a
      minimum duration of follow-up of ten years; twenty-eight of these fifty-eight
      hips had radiographic evidence of acetabular component migration. CONCLUSIONS:
      This bipolar cup, when used for hemiarthroplasty in patients with symptomatic
      arthritis of the hip, was associated with unacceptably high rates of pain,
      migration, osteolysis, and the need for revision to total hip arthroplasty,
      especially when the acetabulum had been reamed. To the extent that these findings
      can be generalized to similar implant designs with conventional polyethylene, we
      do not recommend bipolar hemiarthroplasty as the primary operative treatment for
      degenerative arthritis of the hip.

PMID- 16882909
TI  - Osteonecrosis of the glenoid. A case report.

PMID- 16882910
TI  - Osteolysis and arthropathy of the shoulder after use of bioabsorbable knotless
      suture anchors. A report of four cases.

PMID- 16882908
TI  - Anterior cruciate ligament deficiency alters the in vivo motion of the
      tibiofemoral cartilage contact points in both the anteroposterior and
      mediolateral directions.
AB  - BACKGROUND: Quantifying the effects of anterior cruciate ligament deficiency on
      joint biomechanics is critical in order to better understand the mechanisms of
      joint degeneration in anterior cruciate ligament-deficient knees and to improve
      the surgical treatment of anterior cruciate ligament injuries. We investigated
      the changes in position of the in vivo tibiofemoral articular cartilage contact
      points in anterior cruciate ligament-deficient and intact contralateral knees
      with use of a newly developed dual orthogonal fluoroscopic and magnetic resonance
      imaging technique. METHODS: Nine patients with an anterior cruciate ligament
      rupture in one knee and a normal contralateral knee were recruited. Magnetic
      resonance images were acquired for both the intact and anterior cruciate ligament
      deficient knees to construct computer knee models of the surfaces of the bone and
      cartilage. Each patient performed a single-leg weight-bearing lunge as images
      were recorded with use of a dual fluoroscopic system at full extension and at 15
      degrees , 30 degrees , 60 degrees , and 90 degrees of flexion. The in vivo knee
      position at each flexion angle was then reproduced with use of the knee models
      and fluoroscopic images. The contact points were defined as the centroids of the
      areas of intersection of the tibial and femoral articular cartilage surfaces.
      RESULTS: The contact points moved not only in the anteroposterior direction but
      also in the mediolateral direction in both the anterior cruciate ligament
      deficient and intact knees. In the anteroposterior direction, the contact points
      in the medial compartment of the tibia were more posterior in the anterior
      cruciate ligament-deficient knees than in the intact knees at full extension and
      15 degrees of flexion (p < 0.05). No significant differences were observed with
      regard to the anteroposterior motion of the contact points in the lateral
      compartment of the tibia. In the mediolateral direction, there was a significant
      lateral shift of the contact points in the medial compartment of the tibia toward
      the medial tibial spine between full extension and 60 degrees of flexion (p <
      0.05). The contact points in the lateral compartment of the tibia shifted
      laterally, away from the lateral tibial spine, at 15 degrees and 30 degrees of
      flexion (p < 0.05). CONCLUSIONS: In the presence of anterior cruciate ligament
      injury, the contact points shift both posteriorly and laterally on the surface of
      the tibial plateau. In the medial compartment, the contact points shift toward
      the medial tibial spine, a region where degeneration is observed in patients with
      chronic anterior cruciate ligament injuries.

PMID- 16882911
TI  - Bilateral charnley low-friction arthroplasty with cement in a patient with
      pyknodysostosis. A case report.

PMID- 16882912
TI  - Patellofemoral arthritis.

PMID- 16882913
TI  - An AOA critical issue; how to read the literature to change your practice: an
      evidence-based medicine approach.

PMID- 16882914
TI  - Gainsharing: a primer for orthopaedic surgeons.

PMID- 16882916
TI  - Comparison of short and long arm plaster casts for displaced fractures in the
      distal third of the forearm in children.

PMID- 16882918
TI  - Association of a large lateral extension of the acromion with rotator cuff tears.

PMID- 16882919
TI  - Surgical treatment of femoral fractures in obese children.

PMID- 16882921
TI  - Osteoporotic pertrochanteric fractures can be successfully treated with external
      fixation.

PMID- 16882925
TI  - Simple decompression did not differ from simple decompression plus anterior
      transposition of the nerve for cubital tunnel syndrome.

PMID- 16882924
TI  - A family's request for deception.

PMID- 16882926
TI  - Immediate full weight-bearing mobilization was better than immobilization after
      operative repair of a ruptured achilles tendon.

PMID- 16882927
TI  - 2-octylcyanoacrylate, staples, and sutures had similar wound closure outcomes
      after total hip or knee replacement.

PMID- 16882928
TI  - What's new in spine surgery.

PMID- 16882929
TI  - Metabolically active portion of fat-free mass: a cellular body composition level
      modeling analysis.
AB  - The proportion of fat-free mass (FFM) as body cell mass (BCM) is highly related
      to whole body resting energy expenditure. However, the magnitude of BCM/FFM may
      have been underestimated in previous studies. This is because Moore's equation
      [BCM (kg) = 0.00833 x total body potassium (in mmol)], which was used to predict
      BCM, underestimates BCM by approximately 11%. The aims of the present study were
      to develop a theoretical BCM/FFM model at the cellular level and to explore the
      influences of sex, age, and adiposity on the BCM/FFM. Subjects were 112 adults
      who had the following measurements: total body water by (2)H(2)O or (3)H(2)O
      dilution; extracellular water by NaBr dilution; total body nitrogen by in vivo
      neutron activation analysis; and bone mineral by dual-energy X-ray
      absorptiometry. FFM was calculated using a multicomponent model and BCM as the
      difference between FFM and the sum of extracellular fluid and solids. The
      developed theoretical model revealed that the proportion of BCM to FFM is mainly
      determined by water distribution (i.e., E/I, the ratio of extracellular to
      intracellular water). A significant correlation (r = 0.90, P < 0.001) was present
      between measured and model-predicted BCM/FFM for all subjects pooled. Measured
      BCM/FFM [mean (SD)] was 0.584 +/- 0.041 and 0.529 +/- 0.041 for adult men and
      women (P < 0.001), respectively. A multiple linear regression model showed that
      there are independent significant associations of sex, age, and fat mass with
      BCM/FFM.

PMID- 16882930
TI  - StAR expression and the long-term aldosterone response to high-potassium diet in
      Wistar-Kyoto and spontaneously hypertensive rats.
AB  - ANG II and potassium are known to increase steroidogenic acute regulatory protein
      (StAR) levels. However, a corresponding increase in StAR mRNA levels has so far
      been observed only in response to ANG II. We therefore studied the regulation of
      adrenal StAR mRNA expression in the context of dietary potassium-stimulated
      aldosterone production. Wistar-Kyoto rats (WKY) and spontaneously hypertensive
      rats (SHR) were fed a diet containing either 1 or 4% KCl for 5 days. The high
      potassium diet increased StAR mRNA levels within the zona glomerulosa in both
      strains, as demonstrated by in situ hybridization. However, aldosterone
      production increased in WKY but not in SHR (WKY: from 22.8 +/- 4.8 to 137 +/- 25
      ng/100 ml, P < 0.001, vs. SHR: from 29 +/- 3.8 to 51 +/- 10.2 ng/100 ml, not
      significant). This increase was associated with an increase in Cyp11b2 mRNA
      levels in WKY (3-fold; P < 0.001) but not in SHR. In both strains, the 4% KCl
      diet was associated with increased plasma renin-independent aldosterone
      production, as indicated by the marked increase of the aldosterone-to-renin
      ratios (from 1.4 +/- 0.3 to 9 +/- 3 in WKY and from 3 +/- 1 to 14 +/- 5 in SHR; P
      < 0.002). We conclude that an increase of StAR mRNA levels within the outer
      cortex is involved in the long-term adrenal response to potassium. This increase
      alone is not sufficient to increase aldosterone production in the presence of
      normal Cyp11b2 mRNA levels.

PMID- 16882931
TI  - Prenatal betamethasone exposure results in pituitary-adrenal hyporesponsiveness
      in adult sheep.
AB  - Fetal exposure to synthetic glucocorticoids in sheep results in increased fetal
      hypothalamic-pituitary-adrenal (HPA) activity persisting to one year of age. We
      aimed to determine the effects of single or repeated maternal or fetal
      betamethasone injections on offspring HPA activity at 2 and 3 yr of age and
      whether changes in adrenal mediators of steroidogenesis contribute to changes in
      pituitary-adrenal function. Pregnant ewes or their fetuses received either
      repeated intramuscular saline or betamethasone injections (0.5 mg/kg) at 104,
      111, 118, and 124 days of gestation (dG) or a single betamethasone injection at
      104 dG followed by saline at 111, 118, and 124 dG. Offspring were catheterized at
      2 and 3 yr of age and given corticotrophin-releasing hormone + arginine
      vasopressin challenges. Adrenal tissue was collected for quantitative RT-PCR mRNA
      determination at 3.5 yr of age. In 2-yr-old offspring, maternal betamethasone
      injections did not alter basal ACTH or cortisol levels, but repeated injections
      elevated ACTH responses. At 3 yr of age, basal ACTH was elevated, and both basal
      and stimulated cortisol levels were suppressed by repeated maternal injections.
      Basal and stimulated cortisol-to-ACTH ratios and basal cortisol-to-cytochrome P
      450 17alpha-hydroxylase (P450c17) mRNA ratios were suppressed by repeated
      injections. Repeated fetal betamethasone injections attenuated basal ACTH and
      cortisol levels in offspring at 2 but not 3 yr of age. Plasma changes were not
      associated with altered adrenal P450c17, ACTH receptor, beta-hydroxysteroid
      dehydrogenase, or glucocorticoid receptor mRNA levels. These data suggest that
      maternal, but not fetal, betamethasone administration results in adrenal
      suppression in adulthood.

PMID- 16882932
TI  - Effects of transgenic expression of HIV-1 Vpr on lipid and energy metabolism in
      mice.
AB  - HIV infection is associated with abnormal lipid metabolism, body fat
      redistribution, and altered energy expenditure. The pathogenesis of these complex
      abnormalities is unclear. Viral protein R (Vpr), an HIV-1 accessory protein, can
      regulate gene transcription mediated by the glucocorticoid receptor and
      peroxisome proliferator-activated receptor-gamma and affect mitochondrial
      function in vitro. To test the hypothesis that expression of Vpr in liver and
      adipocytes can alter lipid metabolism in vivo, we engineered mice to express Vpr
      under control of the phosphoenolpyruvate carboxykinase promoter in a tissue
      specific and inducible manner and investigated the effects of dietary fat,
      indinavir, and dexamethasone on energy metabolism and body composition. The
      transgenic mice expressed Vpr mRNA in white and brown adipose tissues and liver
      and immunoaffinity capillary electrophoresis revealed that they had free Vpr
      protein in the plasma. Compared with wild-type (WT) animals, Vpr mice had lower
      plasma triglyceride levels after 6 wk (P < 0.05) but not after 10 wk of a high
      fat diet and lower plasma cholesterol levels after 10 wk of high-fat diet (P <
      0.05). Treatment with dexamethasone obviated group differences, whereas indinavir
      had no significant independent effect on lipids. In the fasted state, Vpr mice
      had a higher respiratory quotient than WT mice (P < 0.05). These data provide the
      first in vivo evidence that HIV-1 Vpr expressed at low levels in adipose tissues
      and liver can 1) circulate in the blood, 2) regulate lipid and fatty acid
      metabolism, and 3) alter fuel selection for oxidation in the fasted state.

PMID- 16882934
TI  - The tango and tangle of human papillomavirus and the human genome.

PMID- 16882933
TI  - Is it time for some new approaches for treating advanced ovarian cancer?

PMID- 16882936
TI  - U.S. girls to receive HPV vaccine but picture unclear on potential worldwide use,
      acceptance.

PMID- 16882935
TI  - Ariad Pharmaceuticals wins first round over Eli Lilly, patents on methods can be
      far-reaching.

PMID- 16882937
TI  - Stat bite: worldwide cervical and uterine cancer incidence and mortality, 2002.

PMID- 16882938
TI  - Senate health plan legislation opposed by ACS.

PMID- 16882939
TI  - State by state comparison of insurance regulations.

PMID- 16882940
TI  - Randomized phase III trial of topotecan following carboplatin and paclitaxel in
      first-line treatment of advanced ovarian cancer: a gynecologic cancer intergroup
      trial of the AGO-OVAR and GINECO.
AB  - BACKGROUND: The combination of carboplatin and paclitaxel is the standard of care
      for the treatment of ovarian cancer, yet rates of recurrence and death remain
      high. We performed a prospective randomized phase III study to examine whether
      sequential administration of topotecan can improve the efficacy of carboplatin
      and paclitaxel in first-line treatment of advanced epithelial ovarian cancer.
      METHODS: A total of 1308 patients with previously untreated ovarian cancer
      (International Federation of Gynecology and Obstetrics stages IIB-IV) were
      randomly assigned to receive six cycles of paclitaxel and carboplatin followed by
      either four cycles of topotecan (TC-Top; 658 patients) or surveillance (TC; 650
      patients) on a 3-week per cycle schedule. The primary endpoint was overall
      survival, and secondary endpoints were progression-free survival, response rate,
      toxicity, and quality of life. Time-to-event data were analyzed using the Kaplan
      Meier method, and a stratified log-rank test was used to compare distributions
      between treatment groups. Hazard ratios (HRs) with 95% confidence intervals (CIs)
      were estimated using a Cox proportional hazards model. Categorical data were
      compared using a stratified Cochran-Mantel-Haenszel test. All statistical tests
      were two-sided. RESULTS: Median progression-free survival was 18.2 months in the
      TC-Top arm versus 18.5 months in the TC arm (stratum-adjusted HR = 0.97 [95% CI =
      0.85 to 1.10]; P = .688). Median overall survival was 43.1 months for the TC-Top
      arm versus 44.5 months for the TC arm (stratum-adjusted HR = 1.01 [95% CI = 0.86
      to 1.18]; P = .885). At 3 years, overall survival in both arms was 57% (58.5% in
      the TC arm and 55.7% in the TC-Top arm). Compared with patients in the TC arm,
      patients in the TC-Top arm had more grade 3-4 hematologic toxic effects
      (requiring more supportive care) and more grade 3-4 infections (5.1% versus 2.7%;
      P = .034) but did not have a statistically significant increase in febrile
      neutropenia (3.3% versus 3.1%; P = .80). Among patients who had measurable
      disease (TC, n = 147; TC-Top, n = 145), overall (i.e., complete or partial)
      response was 69.0% (95% CI = 61.4% to 76.5%) in the TC-Top arm and 76.2% (95% CI
      = 69.3% to 83.1%) in the TC arm (P = .166). CONCLUSIONS: The sequential addition
      of topotecan to carboplatin-paclitaxel did not result in superior overall
      response or progression-free or overall survival. Therefore, this regimen is not
      recommended as standard of care treatment for ovarian cancer.

PMID- 16882941
TI  - Human papillomavirus type 16 and 18 variants: race-related distribution and
      persistence.
AB  - BACKGROUND: Analogous to the geographic distribution of variants of human
      papillomavirus (HPV) types, the distribution and persistence of these variants
      among infected individuals may be related to the racial composition of a
      population living in one geographic region. METHODS: We studied 1114 women in the
      United States participating in the Atypical Squamous Cells of Undetermined
      Significance/Low-Grade Squamous Intraepithelial Lesion Triage Study who were
      positive for HPV16 and/or HPV18 at enrollment. Race was self-reported. HPV
      samples were characterized by sequencing the E6 gene and part of the long control
      region and classified as variants according to established lineages. Subjects
      were examined for HPV every 6 months for 2 years. All statistical tests were two
      sided. RESULTS: HPV18 African variants were predominant in the 97 HPV18-infected
      African American women (i.e., 62 women or 63.9%, 95% confidence interval [CI] =
      53.5% to 73.4%), and European variants were common in the 168 HPV18-infected
      white women (i.e., 91 women or 54.2%, 95% CI = 46.3% to 61.9%). HPV16 African
      variants accounted for 43 (26.5%, 95% CI = 19.9% to 34.0%) of the infections in
      the 162 HPV16-infected African American women but for only 25 (4.3%, 95% CI =
      2.8% to 6.3%) in the 584 HPV16-infected white women. The likelihood of remaining
      HPV18 positive was statistically significantly higher in white women infected
      with European than in white women infected with African variants (P = .04); the
      reverse was observed in African American women (P = .03). A similar pattern was
      observed for persistence of HPV16 variants, with the likelihood of remaining
      positive being higher for white women, but lower for African American women,
      infected with an European variant than with an African variant (P = .03 and P =
      .16, respectively). CONCLUSIONS: Variants of HPV16 and HPV18 appear to persist
      longer in a host whose race indicates an ancestral geographic distribution that
      was once shared with that of the variant-i.e., European variants persist longer
      in white women, and African variants persist longer in African American women.

PMID- 16882942
TI  - Variations in hospice use among cancer patients.
AB  - BACKGROUND: Previous studies have documented that hospice enrollment by
      terminally ill cancer patients varies substantially by patient characteristics
      and across broad geographic regions, but little is known about how local practice
      patterns and individual physicians contribute to these variations. We examined
      hospice use within a regional integrated health care delivery system that
      provides consistent insurance coverage and hospice availability for its members
      to evaluate the relative importance of patient characteristics, physician
      characteristics, individual physicians, and local health centers in explaining
      variations in hospice enrollment. METHODS: We examined data for 3805 Kaiser
      Permanente of Northern California health plan enrollees who were diagnosed with
      and died of lung, colorectal, breast, or prostate cancer from January 1, 1996,
      through June 30, 2001. We used a random-effects linear probability hierarchical
      model to estimate adjusted hospice enrollment rates and identify factors
      associated with hospice enrollment. All P values are two-sided. RESULTS: Overall,
      65.4% of patients enrolled in hospice care before death. In adjusted analyses,
      hospice enrollment did not vary by patients' race/ethnicity or marital status
      (all P>.2) but varied substantially among the 11 health centers where patients
      were treated (standard deviation [SD] of random effect = 10.0 percentage points,
      corresponding to an estimated adjusted hospice enrollment rate for two-thirds of
      centers (2 SDs) ranging from 55% to 75%, P = .02). Hospice enrollment varied less
      among the 675 individual physicians (SD = 4.6 percentage points; P = .09).
      CONCLUSIONS: Health care within a large integrated delivery system has the
      potential to eliminate racial and ethnic disparities in hospice use, but
      substantial variation in hospice use persists among local health centers. Focused
      efforts to understand how patients, physicians, and hospices interact at the
      local level are important to ensure equal access to hospice care for all
      terminally ill cancer patients.

PMID- 16882943
TI  - Effect of disrupted SOX18 transcription factor function on tumor growth,
      vascularization, and endothelial development.
AB  - BACKGROUND: The growth of solid tumors depends on establishing blood supply;
      thus, inhibiting tumor angiogenesis has been a long-term goal in cancer therapy.
      The SOX18 transcription factor is a key regulator of murine and human blood
      vessel formation. METHODS: We established allograft melanoma tumors in wild-type
      mice, Sox18-null mice, and mice expressing a dominant-negative form of Sox18
      (Sox18RaOp) (n = 4 per group) and measured tumor growth and microvessel density
      by immunohistochemical analysis with antibodies to the endothelial marker CD31
      and the pericyte marker NG2. We also assessed the affects of disrupted SOX18
      function on MCF-7 human breast cancer and human umbilical vein endothelial cell
      (HUVEC) proliferation by measuring BrdU incorporation and by MTS assay, cell
      migration using Boyden chamber assay, and capillary tube formation in vitro. All
      statistical tests were two-sided. RESULTS: Allograft tumors in Sox18-null and
      Sox18RaOp mice grew more slowly than those in wild-type mice (tumor volume at day
      14, Sox18 null, mean = 486 mm3, 95% confidence interval [CI] = 345 mm3 to 627
      mm3, P = .004; Sox18RaOp, mean = 233 mm3, 95% CI = 73 mm3 to 119 mm3, P<.001;
      versus wild-type, mean = 817 mm3, 95% CI = 643 mm3 to 1001 mm3) and had fewer
      CD31- and NG2-expressing vessels. Expression of dominant-negative Sox18 reduced
      the proliferation of MCF-7 cells (BrdU incorporation: MCF-7(Ra) = 20%, 95% CI =
      15% to 25% versus MCF-7 = 41%, 95% CI = 35% to 45%; P = .013) and HUVECs (optical
      density at 490 nm, empty vector, mean = 0.46 versus SOX18 mean = 0.29; difference
      = 0.17, 95% CI = 0.14 to 0.19; P = .001) compared with control subjects.
      Overexpression of wild-type SOX18 promoted capillary tube formation of HUVECs in
      vitro, whereas expression of dominant-negative SOX18 impaired tube formation of
      HUVECs and the migration of MCF-7 cells via the disruption of the actin
      cytoskeleton. CONCLUSIONS: SOX18 is a potential target for antiangiogenic therapy
      of human cancers.

PMID- 16882945
TI  - Processed meat consumption and stomach cancer risk: a meta-analysis.
AB  - BACKGROUND: The relationship between processed meat consumption and the risk of
      stomach cancer is controversial. We conducted a meta-analysis to summarize
      available evidence from cohort and case-control studies on this issue. METHODS:
      We searched Medline for studies of processed meat consumption and stomach cancer
      published from January 1966 through March 2006. Random-effects models were used
      to pool the relative risks from individual studies. All statistical tests were
      two-sided. RESULTS: Six prospective cohort studies (involving 2209 stomach cancer
      patients) and nine case-control studies (2495 case patients) were eligible for
      inclusion in the dose-response meta-analysis of processed meat consumption. The
      estimated summary relative risks of stomach cancer for an increase in processed
      meat consumption of 30 g/day, approximately half of an average serving, were 1.15
      (95% confidence interval [CI] = 1.04 to 1.27) for the cohort studies and 1.38
      (95% CI = 1.19 to 1.60) for the case-control studies. There was no statistically
      significant heterogeneity among the cohort studies (P = .42) or among the case
      control studies (P = .19). In three cohort and four case-control studies that
      examined the association between bacon consumption and stomach cancer, the
      summary relative risk was 1.37 (95% CI = 1.17 to 1.61) for the highest versus
      lowest intake categories of bacon, without heterogeneity among these studies (P =
      .66). CONCLUSION: Increased consumption of processed meat is associated with an
      increased risk of stomach cancer. However, the possibility that the association
      may be confounded or modified by other factors cannot be ruled out.

PMID- 16882944
TI  - Antileukemic activity of shepherdin and molecular diversity of hsp90 inhibitors.
AB  - BACKGROUND: Heat shock protein 90 (Hsp90) is a molecular chaperone that is
      involved in signaling pathways for cell proliferation, survival, and cellular
      adaptation. Inhibitors of Hsp90 are being examined as cancer therapeutic agents,
      but the molecular mechanism of their anticancer activity is still unclear. We
      investigated Hsp90 as a therapeutic target for acute myeloid leukemia (AML) by
      use of the Hsp90 inhibitor shepherdin (a novel peptidyl antagonist of the
      interaction between Hsp90 and survivin, which is a regulator of cell
      proliferation and cell viability in cancer). METHODS: We studied protein
      interactions by molecular dynamics simulations and conducted competition
      experiments by use of enzyme-linked immunosorbent assay (ELISA). Shepherdin[79
      83], a novel variant carrying the survivin sequence from Lys-79 through Gly-83,
      or its scrambled peptide was made permeable to cells by adding the antennapedia
      helix III carrier sequence. Apoptosis, Hsp90 client protein expression, and
      mitochondrial dysfunction were evaluated in AML types (myeloblastic, monocytic,
      and chronic myelogenous leukemia in blast crisis), patient-derived blasts, and
      normal mononuclear cells. Effects of shepherdin on tumor growth were evaluated in
      AML xenograft tumors in mice (n = 6). Organ tissues were examined histologically.
      RESULTS: Shepherdin[79-83] bound to Hsp90, inhibited formation of the survivin
      Hsp90 complex, and competed with ATP binding to Hsp90. Cell-permeable
      shepherdin[79-83] induced rapid (within 30 minutes) and complete (with
      concentrations inducing 50% cell death of 24-35 microM) killing of AML types and
      blasts, but it did not affect normal mononuclear cells. Shepherdin[79-83] made
      contact with unique residues in the ATP pocket of Hsp90 (Ile-96, Asp-102, and Phe
      138), did not increase Hsp70 levels in AML cells, disrupted mitochondrial
      function within 2 minutes of treatment, and eliminated the expression of Hsp90
      client proteins. Shepherdin[79-83] abolished growth of AML xenograft tumors (mean
      of control group = 1698 mm3 and mean of treated group = 232 mm3; difference =
      1466 mm3, 95% confidence interval = 505.8 to 2426; P = .008) without systemic or
      organ toxicity and inhibited Hsp90 function in vivo. CONCLUSIONS: Shepherdin is a
      novel Hsp90 inhibitor with a unique mechanism of anticancer activity.

PMID- 16882946
TI  - Highly active antiretroviral therapy and human immunodeficiency virus-associated
      primary cerebral lymphoma.
AB  - From a cohort of 9621 human immunodeficiency virus type 1-infected individuals,
      we identified 61 patients with primary central nervous system lymphoma (PCL) who
      had a median survival of 1.3 months. We compared clinicopathologic variables of
      patients who were treated in the pre-highly active antiretroviral therapy (HAART)
      and HAART eras and investigated whether exposure to antiretroviral agents with
      differing cerebrospinal fluid penetrations was associated with risk for PCL. All
      statistical tests were two-sided. Incidence of PCL was lower in the HAART era
      (1.2 cases per 1000 patient-years, 95% confidence interval [CI] = 0.8 to 1.9)
      than in the pre-HAART era (three cases per 1000 years, 95% CI = 2.1 to 4.0;
      P<.001), and overall survival was longer (median survival = 32 days, range = 5
      315 days, versus 48 days, range = 15-1136 days; log rank P = .03). In the HAART
      era, fewer patients had prior acquired immunodeficiency syndrome-defining
      illnesses than in the pre-HAART era (64% versus 90%; P = .013), and patients were
      more likely to have the diagnosis of PCL confirmed histologically or by
      polymerase chain reaction (77% versus 26%; P<.001). Exposure to specific
      antiretroviral agents was not associated with risk for PCL.

PMID- 16882947
TI  - Identifying the variables impacting post-burn psychological adjustment: a meta
      analysis.
AB  - OBJECTIVE: The purpose of this study was to identify and evaluate variables that
      have the greatest impact on psychological adjustment after burn injury among
      children, adolescents, and young adults. METHODS: Meta-analytical procedures were
      utilized to determine the strength of association indices of identified impact
      variables. Only 13 articles were utilized due to the scarcity of and statistical
      limitations of the research. RESULTS: The body location variable (.26) had the
      greatest mean strength of association in relation to psychological adjustment.
      The burn injury variable (.21) had the second greatest mean strength of
      association. Finally, both the parental adjustment variable and the child
      premorbid psychological functioning variable (.15) had the third greatest mean
      strength of association. CONCLUSIONS: A major implication of this research is
      that the impact variables identified will be useful in targeting burn patients
      who are at risk for psychological adjustment problems.

PMID- 16882948
TI  - The cover. Mad Dog.

PMID- 16882949
TI  - A piece of my mind. Heart opening.

PMID- 16882950
TI  - Katrina survivors strive to reclaim their lives.

PMID- 16882951
TI  - Experts work to prevent college suicides.

PMID- 16882952
TI  - Rape at US colleges often fueled by alcohol.

PMID- 16882953
TI  - Radiation exposure and thyroid disease in Hiroshima and Nagasaki atomic bomb
      survivors.

PMID- 16882954
TI  - Radiation exposure and thyroid cancer.

PMID- 16882955
TI  - Mental health after deployment to Iraq or Afghanistan.

PMID- 16882956
TI  - Mental health after deployment to Iraq or Afghanistan.

PMID- 16882957
TI  - Epidemiology of injuries and deaths from landmines and unexploded ordnance in
      Chechnya, 1994 through 2005.

PMID- 16882958
TI  - Neuropsychological outcomes of army personnel following deployment to the Iraq
      war.
AB  - CONTEXT: The effects of war-zone deployment on neuropsychological health remain
      poorly understood. Neuropsychological performance deficits serve as sensitive
      measures of neural dysfunction and are often associated with psychosocial and
      occupational problems. Previous studies have not conducted objective
      neuropsychological assessments both before and after a major war-zone deployment.
      OBJECTIVE: To examine objective neuropsychological outcomes of Iraq War
      deployment in a large military cohort. DESIGN, SETTING, AND PARTICIPANTS: The
      Neurocognition Deployment Health Study, a prospective, cohort-controlled study
      conducted at military installations. This report centers on 961 male and female
      active-duty Army soldiers drawn from the larger cohort. Deploying Army soldiers
      (n = 654) were examined prior to deployment to Iraq (April-December 2003) and
      shortly after return (within a mean of 73 days [median, 75 days]; January-May
      2005) from Iraq deployment. A comparison group of soldiers (n = 307) similar in
      military characteristics but not deploying overseas during the study was assessed
      in sessions timed to be as close as possible to the assessment of deployers.
      Military unit sampling procedures facilitated representation of combat, combat
      support, and combat service support functions among both deployers and
      nondeployers. MAIN OUTCOME MEASURES: Individually administered, performance-based
      neuropsychological tasks. Estimates (beta; the unstandardized parameter estimate)
      for the absolute differences in adjusted mean outcome scores between deployed and
      nondeployed groups were determined using generalized estimating equations.
      RESULTS: Multiple linear regression analyses adjusted for battalion membership
      revealed that Iraq deployment, compared with nondeployment, was associated with
      neuropsychological compromise on tasks of sustained attention (beta = 0.11;
      P<.001), verbal learning (beta = -1.51; P = .003), and visual-spatial memory
      (beta = -3.82; P<.001). Iraq deployment was also associated with increased
      negative state affect on measures of confusion (beta = 1.40; P<.001) and tension
      (beta = 1.24; P<.001). In contrast, deployment was associated with improved
      simple reaction time (beta = 4.30; P = .003). Deployment effects remained
      statistically significant after taking into account deployment-related head
      injury and stress and depression symptoms. CONCLUSIONS: Deployment to Iraq is
      associated with increased risk of neuropsychological compromise. Findings point
      to the need to investigate further the impact of deployment on neural
      functioning. Public health implications include consideration of
      neuropsychological compromise in health prevention and postdeployment clinical
      and occupational management.

PMID- 16882959
TI  - Approaches to screening for intimate partner violence in health care settings: a
      randomized trial.
AB  - CONTEXT: Screening for intimate partner violence (IPV) in health care settings
      has been recommended by some professional organizations, although there is
      limited information regarding the accuracy, acceptability, and completeness of
      different screening methods and instruments. OBJECTIVE: To determine the optimal
      method for IPV screening in health care settings. DESIGN AND SETTING: Cluster
      randomized trial conducted from May 2004 to January 2005 at 2 each of emergency
      departments, family practices, and women's health clinics in Ontario, Canada.
      PARTICIPANTS: English-speaking women aged 18 to 64 years who were well enough to
      participate and could be seen individually were eligible. Of 2602 eligible women,
      141 (5%) refused participation. INTERVENTION: Participants were randomized by
      clinic day or shift to 1 of 3 screening approaches: a face-to-face interview with
      a health care provider (physician or nurse), written self-completed
      questionnaire, and computer-based self-completed questionnaire. Two screening
      instruments-the Partner Violence Screen (PVS) and the Woman Abuse Screening Tool
      (WAST)-were administered and compared with the Composite Abuse Scale (CAS) as the
      criterion standard. MAIN OUTCOME MEASURES: The approaches were evaluated on
      prevalence, extent of missing data, and participant preference. Agreement between
      the screening instruments and the CAS was examined. RESULTS: The 12-month
      prevalence of IPV ranged from 4.1% to 17.7%, depending on screening method,
      instrument, and health care setting. Although no statistically significant main
      effects on prevalence were found for method or screening instrument, a
      significant interaction between method and instrument was found: prevalence was
      lower on the written WAST vs other combinations. The face-to-face approach was
      least preferred by participants. The WAST and the written format yielded
      significantly less missing data than the PVS and other methods. The PVS and WAST
      had similar sensitivities (49.2% and 47.0%, respectively) and specificities
      (93.7% and 95.6%, respectively). CONCLUSIONS: In screening for IPV, women
      preferred self-completed approaches over face-to-face questioning; computer-based
      screening did not increase prevalence; and written screens had fewest missing
      data. These are important considerations for both clinical and research efforts
      in IPV screening. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00336297.

PMID- 16882960
TI  - Mental health problems among adults in tsunami-affected areas in southern
      Thailand.
AB  - CONTEXT: On December 26, 2004, an undersea earthquake occurred off the
      northwestern coast of Sumatra, Indonesia. The tsunami that followed severely
      affected all 6 southwestern provinces of Thailand, where 5395 individuals died,
      2991 were unaccounted for, and 8457 were injured. OBJECTIVE: To assess the
      prevalence of symptoms of posttraumatic stress disorder (PTSD), anxiety, and
      depression among individuals residing in areas affected by the tsunami in
      southern Thailand as part of a public health emergency response and rapid
      assessment. DESIGN, SETTING, AND PARTICIPANTS: A multistage, cluster, population
      based mental health survey was conducted from February 15 to 22, 2005, of random
      samples of displaced (n = 371) and nondisplaced persons in Phang Nga province (n
      = 322) and nondisplaced persons in the provinces of Krabi and Phuket (n = 368).
      Data were collected using an interviewer-administered questionnaire on handheld
      computers. A surveillance follow-up survey of the displaced persons (n = 371) and
      nondisplaced persons (n = 322) in Phang Na was conducted in September 2005. MAIN
      OUTCOMES MEASURES: Medical Outcomes Study-36 Short-Form Health Survey SF-36 to
      assess self-perceived general health, bodily pain, and social and emotional
      functioning; the Harvard Trauma Questionnaire to assess tsunami-specific
      traumatic events; and the Hopkins Checklist-25 to detect symptoms of anxiety and
      depression. RESULTS: Participation rates for displaced and nondisplaced persons
      in the rapid assessment survey were 69% and 58%, respectively. Symptoms of PTSD
      were reported by 12% of displaced and 7% of nondisplaced persons in Phang Nga and
      3% of nondisplaced persons in Krabi and Phuket. Anxiety symptoms were reported by
      37% of displaced and 30% of nondisplaced persons in Phang Nga and 22% of
      nondisplaced persons in Krabi and Phuket. Symptoms of depression were reported by
      30% of displaced and 21% of nondisplaced persons in Phang Nga and 10% of
      nondisplaced persons in Krabi and Phuket. In multivariate analysis, loss of
      livelihood was independently and significantly associated with symptoms of all 3
      mental health outcomes (PTSD, anxiety, and depression). In the 9-month follow-up
      surveillance survey of 270 (73%) displaced and 250 (80%) nondisplaced
      participants in Phang Nga, prevalence rates of symptoms of PTSD, anxiety, and
      depression among displaced persons decreased to 7%, 24.8%, and 16.7%,
      respectively, and among nondisplaced persons, prevalence rates decreased to 2.3%,
      25.9%, and 14.3%, respectively. CONCLUSIONS: Among survivors of the tsunami in
      southern Thailand, elevated rates of symptoms of PTSD, anxiety, and depression
      were reported 8 weeks after the disaster, with higher rates for anxiety and
      depression than PTSD symptoms. Nine months after the disaster, the rates of those
      reporting these symptoms decreased but were still elevated. This information is
      important for directing, strengthening, and evaluating posttsunami mental health
      needs and interventions.

PMID- 16882961
TI  - Symptoms of posttraumatic stress disorder and depression among children in
      tsunami-affected areas in southern Thailand.
AB  - CONTEXT: On December 26, 2004, an undersea earthquake occurred off the
      northwestern coast of Sumatra, Indonesia. The tsunami that followed severely
      impacted all 6 southwestern provinces of Thailand, where approximately 20,000
      children were directly affected. OBJECTIVE: To assess trauma experiences and the
      prevalence of symptoms of posttraumatic stress disorder (PTSD) and depression
      among children in tsunami-affected provinces in southern Thailand. DESIGN,
      SETTING, AND PARTICIPANTS: Population-based mental health surveys were conducted
      among children aged 7 to 14 years in Phang Nga, Phuket, and Krabi provinces from
      February 15-22, 2005 (2 months posttsunami), and September 7-12, 2005 (9 months
      posttsunami). MAIN OUTCOME MEASURES: Trauma experiences and symptoms of PTSD and
      depression as measured by a tsunami-modified version of the PsySTART Rapid Triage
      System, the UCLA PTSD Reaction Index, and the Birleson Depression Self-Rating
      Scale. RESULTS: A total of 371 children (167 displaced and living in camps, 99
      not displaced from villages affected by the tsunami, and 105 not displaced from
      unaffected villages) participated in the first survey. The prevalence rates of
      PTSD symptoms were 13% among children living in camps, 11% among children from
      affected villages, and 6% among children from unaffected villages (camps vs
      unaffected villages, P = .25); for depression symptoms, the prevalence rates were
      11%, 5%, and 8%, respectively (P = .39). In multivariate analysis of the first
      assessment, having had a delayed evacuation, having felt one's own or a family
      member's life to have been in danger, and having felt extreme panic or fear were
      significantly associated with PTSD symptoms. Older age and having felt that their
      own or a family member's life had been in danger were significantly associated
      with depression symptoms. In the follow-up survey, 72% (151/210) of children from
      Phang Nga participated. Prevalence rates of symptoms of PTSD and depression among
      these children did not decrease significantly over time. CONCLUSIONS: This
      assessment documents the prevalence of mental health problems among children in
      tsunami-affected provinces in southern Thailand at 2 and 9 months posttsunami.
      Traumatic events experienced during the tsunami were significantly associated
      with symptoms of PTSD and depression. These data may be useful to target mental
      health services for children and may inform the design of these interventions.

PMID- 16882962
TI  - Anxiety, depression, and posttraumatic stress in Iranian survivors of chemical
      warfare.
AB  - CONTEXT: In the 1980-1988 Iran-Iraq War, extensive use of chemical weapons
      resulted in high rates of morbidity and mortality. While much is known about the
      physical consequences of chemical warfare, there is a paucity of information
      about the long-term effects of chemical attacks on mental health. OBJECTIVE: To
      assess the long-term psychological impact of chemical warfare on a civilian
      population. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional randomized survey
      conducted in July 2004 of 153 civilians in 3 towns exposed to warfare in
      northwestern Iran: Oshnaviyeh (low-intensity conventional warfare), Rabat (high
      intensity conventional warfare), and Sardasht (both high-intensity conventional
      warfare and chemical weapons). MAIN OUTCOME MEASURES: Full or partial
      posttraumatic stress disorder (PTSD) diagnosis, anxiety symptoms, and depressive
      symptoms were assessed using Farsi versions of the Clinician-Administered PTSD
      Scale, Hamilton Scale for Anxiety, and Beck Depression Inventory, respectively.
      RESULTS: Overall participation rate was 93%. Respondents had a mean age of 45
      years and were all of Kurdish ethnicity. Among individuals exposed to both high
      intensity warfare and chemical weapons, prevalence rates for lifetime PTSD,
      current PTSD, major anxiety symptoms, and severe depressive symptoms were 59%,
      33%, 65%, and 41%, respectively. Among the low-intensity warfare group, the
      corresponding rates were 8%, 2%, 18%, and 6%, respectively, while intermediate
      rates were found among those exposed to high-intensity warfare but not to
      chemical weapons (31%, 8%, 26%, and 12%, respectively). Compared with individuals
      exposed to low-intensity warfare, those exposed to both high-intensity warfare
      and chemical weapons were at higher risk for lifetime PTSD (odds ratio [OR],
      18.6; 95% confidence interval [CI], 5.8-59.4), current PTSD (OR, 27.4; 95% CI,
      3.4-218.2), increased anxiety symptoms (OR, 14.6; 95% CI, 6.0-35.6), and
      increased depressive symptoms (OR, 7.2; 95% CI, 3.3-15.9). Exposure to high
      intensity warfare but not to chemical weapons was also significantly associated
      with lifetime PTSD (OR, 5.4; 95% CI, 1.7-17.6), compared with those in the low
      intensity warfare group. Further, compared with individuals exposed to high
      intensity warfare alone, those exposed to both high-intensity warfare and
      chemical weapons were at higher risk for lifetime PTSD (OR, 3.4; 95% CI, 1.5
      7.4), current PTSD (OR, 6.2; 95% CI, 2.0-20.1), increased anxiety symptoms (OR,
      5.6; 95% CI, 2.5-12.6), and increased depressive symptoms (OR, 3.7; 95% CI, 1.8
      7.2). CONCLUSION: Exposure to chemical warfare is an extreme traumatic event that
      has long-lasting adverse consequences on mental health.

PMID- 16882963
TI  - Symptomatic hyponatremia during treatment of dehydrating diarrheal disease with
      reduced osmolarity oral rehydration solution.
AB  - CONTEXT: In May 2002, the World Health Organization and the United Nations
      Children's Fund recommended that the formulation of oral rehydration solution
      (ORS) for treatment of patients with diarrhea be changed to one with a reduced
      osmolarity and that safety of the new formulation, particularly development of
      symptomatic hyponatremia, be monitored. OBJECTIVE: To measure the rates of
      symptomatic hyponatremia during treatment of patients with diarrhea with reduced
      osmolarity ORS. DESIGN, SETTINGS, AND PATIENTS: A phase 4 trial conducted at the
      Dhaka hospital (December 1, 2002-November 30, 2003) and Matlab hospital (February
      2, 2003-January 31, 2004) of the International Centre for Diarrhoeal Disease
      Research Bangladesh: Centre for Health and Population Research, Dhaka,
      Bangladesh. All patients admitted with uncomplicated watery diarrhea were treated
      with the newly recommended ORS and monitored. Patients developing neurological
      symptoms (seizure or altered consciousness) were transferred to the special care
      ward for treatment and investigated to identify the cause of the symptoms.
      Patient records of the Dhaka hospital were reviewed during the previous year when
      the old ORS formulation was used. INTERVENTION: Reduced osmolarity ORS. MAIN
      OUTCOME MEASURE: Incidence rate of symptomatic hyponatremia in a 1-year period.
      RESULTS: A total of 53,280 patients, including 22,536 children younger than 60
      months, were monitored at the Dhaka and Matlab hospitals. Twenty-four patients,
      none older than 36 months, developed seizures or altered consciousness associated
      with hyponatremia, with an overall incidence rate of 0.05% (95% confidence
      interval [CI], 0.03%-0.07%) at the Dhaka hospital and 0.03% (95% CI, 0.01%-0.09%)
      at the Matlab hospital. During the previous year, 47 patients at the Dhaka
      hospital had symptoms associated with hyponatremia, for an estimated incidence
      rate of 0.10% (95% CI, 0.07%-0.13%). The reduction in the rates was statistically
      significant (odds ratio, 0.50; 95% CI, 0.29-0.85; P = .009). CONCLUSION: The risk
      of symptoms associated with hyponatremia in patients treated with the reduced
      osmolarity ORS is minimal and did not increase with the change in formulation.

PMID- 16882964
TI  - Neuropsychological changes following military service in Iraq: case proven, but
      what is the significance?

PMID- 16882965
TI  - Rapid assessments of mental health needs after disasters.

PMID- 16882966
TI  - War and children.

PMID- 16882967
TI  - Maternal famine, de novo mutations, and schizophrenia.

PMID- 16882968
TI  - Mental health and recovery in the Gulf Coast after Hurricanes Katrina and Rita.

PMID- 16882969
TI  - JAMA patient page. Posttraumatic stress disorder.

PMID- 16882970
TI  - A 5' RNA element promotes dengue virus RNA synthesis on a circular genome.
AB  - The mechanisms of RNA replication of plus-strand RNA viruses are still unclear.
      Here, we identified the first promoter element for RNA synthesis described in a
      flavivirus. Using dengue virus as a model, we found that the viral RdRp
      discriminates the viral RNA by specific recognition of a 5' element named SLA. We
      demonstrated that RNA-RNA interactions between 5' and 3' end sequences of the
      viral genome enhance dengue virus RNA synthesis only in the presence of an intact
      SLA. We propose a novel mechanism for minus-strand RNA synthesis in which the
      viral polymerase binds SLA at the 5' end of the genome and reaches the site of
      initiation at the 3' end via long-range RNA-RNA interactions. These findings
      provide an explanation for the strict requirement of dengue virus genome
      cyclization during viral replication.

PMID- 16882971
TI  - Extensive post-transcriptional regulation of microRNAs and its implications for
      cancer.
AB  - MicroRNAs (miRNAs) are short, noncoding RNAs that post-transcriptionally regulate
      gene expression. While hundreds of mammalian miRNA genes have been identified,
      little is known about the pathways that regulate the production of active miRNA
      species. Here we show that a large fraction of miRNA genes are regulated post
      transcriptionally. During early mouse development, many miRNA primary
      transcripts, including the Let-7 family, are present at high levels but are not
      processed by the enzyme Drosha. An analysis of gene expression in primary tumors
      indicates that the widespread down-regulation of miRNAs observed in cancer is due
      to a failure at the Drosha processing step. These data uncover a novel regulatory
      step in miRNA function and provide a mechanism for miRNA down-regulation in
      cancer.

PMID- 16882973
TI  - TXR1-mediated thrombospondin repression: a novel mechanism of resistance to
      taxanes?

PMID- 16882972
TI  - Specific association of Piwi with rasiRNAs derived from retrotransposon and
      heterochromatic regions in the Drosophila genome.
AB  - In Drosophila, Piwi (P-element-induced wimpy testis), which encodes a protein of
      the Argonaute family, is essential for germ stem cell self-renewal. Piwi has
      recently been shown to be a nuclear protein involved in gene silencing of
      retrotransposons and controlling their mobilization in the male germline.
      However, little is known about the molecular mechanisms of Piwi-dependent gene
      silencing. Here we show that endogenous Piwi immunopurified from ovary
      specifically associates with small RNAs of 25-29 nucleotides in length. Piwi
      associated small RNAs were identified by cloning and sequencing as repeat
      associated small interfering RNAs (rasiRNAs) derived from repetitive regions,
      such as retrotransposon and heterochromatic regions, in the Drosophila genome.
      Northern blot analyses revealed that in vivo Piwi does not associate with
      microRNAs (miRNAs) and that guide siRNA was not loaded onto Piwi when siRNA
      duplex was added to ovary lysate. In vitro, recombinant Piwi exhibits target RNA
      cleavage activity. These data together imply that Piwi functions in nuclear RNA
      silencing as Slicer by associating specifically with rasiRNAs originating from
      repetitive targets.

PMID- 16882974
TI  - Does Pol I talk to Pol II? Coordination of RNA polymerases in ribosome
      biogenesis.

PMID- 16882975
TI  - SUMO-mediated regulation of synaptonemal complex formation during meiosis.

PMID- 16882976
TI  - Small RNAs just got bigger: Piwi-interacting RNAs (piRNAs) in mammalian testes.
AB  - Small RNAs constitute a large family of regulatory molecules with diverse
      functions in eukaryotes. Hallmarks of small RNAs are their dependence on double
      stranded RNAs (dsRNA)-specific RNase III-type enzymes for biogenesis and their
      association with Argonaute family proteins for the silencing process. At least
      two classes of small RNAs have previously been described: microRNAs (miRNAs)
      derived from hairpin-shaped precursors and small interfering RNAs (siRNAs)
      generated from long dsRNAs. Recent articles reported a novel class of small RNAs
      that are expressed specifically and abundantly in the spermatogenic cells of
      mice. These RNAs are bigger (26-31 nucleotides [nt]) than most previously
      described small RNAs (21-23 nt) and are associated with Piwi-subclade members of
      the Argonaute protein family. Although the biogenesis and function of these RNAs
      are yet to be determined, these findings may add new dimensions in small RNA
      biology and germline cell biology.

PMID- 16882977
TI  - Plant hormone receptors: perception is everything.
AB  - Despite the bewildering ability of higher plants to change their development with
      respect to the environment, there appear to be only a few hormones that function
      to organize growth and development. With the recent identification of three plant
      hormone receptors, the molecular identities of all the major plant receptors are
      now known. Some plant hormones such as cytokinins, ethylene, and brassinosteroids
      (BR) use well-characterized signaling modules such as those involving receptor
      kinases, but in the case of the ethylene and BR receptors, there appear to be
      additional functions aside from the hormone they perceive. Auxin and gibberellin
      perception require unique mechanisms where the receptors are components involved
      in ubiquitination-dependent proteolysis. With plant hormone receptors in hand,
      comparisons can now be made between plants and other kingdoms as to how hormones
      control growth and development.

PMID- 16882978
TI  - Nucleosome displacement in transcription.
AB  - Recent reports reinforce the notion that nucleosomes are highly dynamic in
      response to the process of transcription. Nucleosomes are displaced at promoters
      during gene activation in a process that involves histone modification, ATP
      dependent nucleosome remodeling complexes, histone chaperones and perhaps histone
      variants. During transcription elongation nucleosomes are acetylated and
      transferred behind RNA polymerase II where they are required to suppress spurious
      transcription initiation within the body of the gene. It is becoming increasingly
      clear that the eukaryotic transcriptional machinery is adapted to exploit the
      presence of nucleosomes in very sophisticated ways.

PMID- 16882979
TI  - Cytokines regulate postnatal hematopoietic stem cell expansion: opposing roles of
      thrombopoietin and LNK.
AB  - The role of cytokines as regulators of hematopoietic stem cell (HSC) expansion
      remains elusive. Herein, we identify thrombopoietin (THPO) and the cytokine
      signaling inhibitor LNK, as opposing physiological regulators of HSC expansion.
      Lnk(-/-) HSCs continue to expand postnatally, up to 24-fold above normal by 6 mo
      of age. Within the stem cell compartment, this expansion is highly selective for
      self-renewing long-term HSCs (LT-HSCs), which show enhanced THPO responsiveness.
      Lnk(-/-) HSC expansion is dependent on THPO, and 12-wk-old Lnk(-/-)Thpo(-/-) mice
      have 65-fold fewer LT-HSCs than Lnk(-/-) mice. Expansions of multiple myeloid,
      but not lymphoid, progenitors in Lnk(-/-) mice also proved THPO-dependent.

PMID- 16882980
TI  - Skin epidermis lacking the c-Myc gene is resistant to Ras-driven tumorigenesis
      but can reacquire sensitivity upon additional loss of the p21Cip1 gene.
AB  - The target gene(s) required for Myc-mediated tumorigenesis are still elusive.
      Here we show that while endogenous c-Myc is surprisingly dispensable for skin
      homeostasis and TPA-induced hyperplasia, c-Myc-deficient epidermis is resistant
      to Ras-mediated DMBA/TPAinduced tumorigenesis. This is mechanistically linked to
      p21(Cip1), which is induced in tumors by the activated Ras-ERK pathway but
      repressed by c-Myc. Acute elimination of c-Myc in established tumors leads to the
      up-regulation of p21(Cip1), and epidermis lacking both p21(Cip1) and c-Myc
      reacquires normal sensitivity to DMBA/TPA-induced tumorigenesis. This identifies
      c-Myc-mediated repression of p21(Cip1) as a key step for Ras-driven epidermal
      tumorigenesis.

PMID- 16882981
TI  - The transcriptional activity of RNA polymerase I is a key determinant for the
      level of all ribosome components.
AB  - Regulation of ribosome biogenesis is a key element of cell biology, not only
      because ribosomes are directly required for growth, but also because ribosome
      production monopolizes nearly 80% of the global transcriptional activity in
      rapidly growing yeast cells. These observations underscore the need for a tight
      regulation of ribosome synthesis in response to environmental conditions. In
      eukaryotic cells, ribosome synthesis involves the activities of the three nuclear
      RNA polymerases (Pol). Although postulated, there is no clear evidence indicating
      whether the maintenance of an equimolar supply of ribosomal components reflects
      communication between the nuclear transcriptional machineries. Here, by
      constructing a yeast strain expressing a Pol I that remains constitutively
      competent for the initiation of transcription under stress conditions, we
      demonstrate that derepression of Pol I transcription leads to a derepression of
      Pol II transcription that is restricted to the genes encoding ribosomal proteins.
      Furthermore, we show that the level of 5S rRNA, synthesized by Pol III, is
      deregulated concomitantly with Pol I transcription. Altogether, these results
      indicate that a partial derepression of Pol I activity drives an abnormal
      accumulation of all ribosomal components, highlighting the critical role of the
      regulation of Pol I activity within the control of ribosome biogenesis.

PMID- 16882983
TI  - In vivo commitment to yeast cotranscriptional splicing is sensitive to
      transcription elongation mutants.
AB  - Spliceosome assembly in the budding yeast Saccharomyces cerevisiae was recently
      shown to occur at the site of transcription. However, evidence for
      cotranscriptional splicing as well as for coupling between transcription and
      splicing is still lacking. Using modifications of a previously published
      chromatin immunoprecipitation (ChIP) assay, we show that cotranscriptional
      splicing occurs approximately 1 kb after transcription of the 3' splice site
      (3'SS). This pathway furthermore protects most intron-containing nascent
      transcripts from the effects of cleavage by an intronic hammerhead ribozyme. This
      suggests that a high percentage of introns are recognized cotranscriptionally.
      This observation led us to screen a small deletion library for strains that
      sensitize a splicing reporter to ribozyme cleavage. Characterization of the
      Deltamud2 strain indicates that the early splicing factor Mud2p functions with U1
      snRNP to form a cross-intron bridging complex on nascent pre-mRNA. The complex
      helps protect the transcript from ribozyme-mediated destruction and suggests an
      intron-definition event early in the spliceosome assembly process. The
      transcription elongation mutant strains Deltadst1 and Deltapaf1 show different
      cotranscriptional splicing phenotypes, suggesting that different transcription
      pathways differentially impact the efficiency of nascent intron definition.

PMID- 16882984
TI  - E4F1: a novel candidate factor for mediating BMI1 function in primitive
      hematopoietic cells.
AB  - The Polycomb group gene Bmi1 is essential for the proliferation of neural and
      hematopoietic stem cells. Much remains to be learned about the pathways involved
      in the severe hematopoietic phenotype observed in Bmi1 homozygous mutant mice
      except for the fact that loss of p53 or concomitant loss of p16(Ink4a) and
      p19(Arf) functions achieves only a partial rescue. Here we report the
      identification of E4F1, an inhibitor of cellular proliferation, as a novel BMI1
      interacting partner in hematopoietic cells. We provide evidence that Bmi1 and
      E4f1 genetically interact in the hematopoietic compartment to regulate cellular
      proliferation. Most importantly, we demonstrate that reduction of E4f1 levels
      through RNA interference mediated knockdown is sufficient to rescue the
      clonogenic and repopulating ability of Bmi1(-/-) hematopoietic cells up to 3 mo
      post-transplantation. Using cell lines and MEF, we also demonstrate that
      INK4A/ARF and p53 are not essential for functional interaction between Bmi1 and
      E4f1. Together, these findings identify E4F1 as a key modulator of BMI1 activity
      in primitive hematopoietic cells.

PMID- 16882982
TI  - Histone trimethylation and the maintenance of transcriptional ON and OFF states
      by trxG and PcG proteins.
AB  - Polycomb group (PcG) and trithorax group (trxG) proteins act as antagonistic
      regulators to maintain transcriptional OFF and ON states of HOX and other target
      genes. To study the molecular basis of PcG/trxG control, we analyzed the
      chromatin of the HOX gene Ultrabithorax (Ubx) in Ubx(OFF)and Ubx(ON)cells
      purified from developing Drosophila. We find that PcG protein complexes PhoRC,
      PRC1, and PRC2 and the Trx protein are all constitutively bound to Polycomb
      response elements (PREs) in the OFF and ON state. In contrast, the trxG protein
      Ash1 is only bound in the ON state; not at PREs but downstream of the
      transcription start site. In the OFF state, we find extensive trimethylation at
      H3-K27, H3-K9, and H4-K20 across the entire Ubx gene; i.e., throughout the
      upstream control, promoter, and coding region. In the ON state, the upstream
      control region is also trimethylated at H3-K27, H3-K9, and H4-K20, but all three
      modifications are absent in the promoter and 5' coding region. Our analyses of
      mutants that lack the PcG histone methyltransferase (HMTase) E(z) or the trxG
      HMTase Ash1 provide strong evidence that differential histone lysine
      trimethylation at the promoter and in the coding region confers transcriptional
      ON and OFF states of Ubx. In particular, our results suggest that PRE-tethered
      PcG protein complexes act over long distances to generate Pc-repressed chromatin
      that is trimethylated at H3-K27, H3-K9, and H4-K20, but that the trxG HMTase Ash1
      selectively prevents this trimethylation in the promoter and coding region in the
      ON state.

PMID- 16882985
TI  - Hda-mediated inactivation of the DnaA protein and dnaA gene autoregulation act in
      concert to ensure homeostatic maintenance of the Escherichia coli chromosome.
AB  - Initiation of DNA replication in Eschericia coli requires the ATP-bound form of
      the DnaA protein. The conversion of DnaA-ATP to DnaA-ADP is facilitated by a
      complex of DnaA, Hda (homologous to DnaA), and DNA-loaded beta-clamp proteins in
      a process termed RIDA (regulatory inactivation of DnaA). Hda-deficient cells
      initiate replication at each origin mainly once per cell cycle, and the rare
      reinitiation events never coincide with the end of the origin sequestration
      period. Therefore, RIDA is not the predominant mechanism to prevent immediate
      reinitiation from oriC. The cellular level of Hda correlated directly with dnaA
      gene expression such that Hda deficiency led to reduced dnaA gene expression, and
      overproduction of Hda led to DnaA overproduction. Hda-deficient cells were very
      sensitive to variations in the cellular level of DnaA, and DnaA overproduction
      led to uncontrolled initiation of replication from oriC, causing severe growth
      retardation or cell death. Based on these observations, we propose that both RIDA
      and dnaA gene autoregulation are required as homeostatic mechanisms to ensure
      that initiation of replication occurs at the same time relative to cell mass in
      each cell cycle.

PMID- 16882986
TI  - Rep and PriA helicase activities prevent RecA from provoking unnecessary
      recombination during replication fork repair.
AB  - The rescue of replication forks stalled on the template DNA was investigated
      using an assay for synthetic lethality that provides a visual readout of cell
      viability and permits investigation of why certain mutations are lethal when
      combined. The results presented show that RecA and other recombination proteins
      are often engaged during replication because RecA is present and provokes
      recombination rather than because recombination is necessary. This occurs
      particularly frequently in cells lacking the helicase activities of Rep and PriA.
      We propose that these two proteins normally limit the loading of RecA on ssDNA
      regions exposed on the leading strand template of damaged forks, and do so by
      unwinding the nascent lagging strand, thus facilitating reannealing of the
      parental strands. Gap closure followed by loading of the DnaB replicative
      helicase enables synthesis of the leading strand to continue. Without either
      activity, RecA loads more frequently on the DNA and drives fork reversal, which
      creates a chickenfoot structure and a requirement for other recombination
      proteins to re-establish a viable fork. The assay also reveals that stalled
      transcription complexes are common impediments to fork progression, and that
      damaged forks often reverse independently of RecA.

PMID- 16882987
TI  - Expression of endometrial glycogen synthase kinase-3beta protein throughout the
      menstrual cycle and its regulation by progesterone.
AB  - Glycogen synthase kinase-3beta (GSK-3beta) is a serine/threonine kinase that
      plays a role in glycogen synthesis by inhibiting glycogen synthase (GS) through
      phosphorylation. We hypothesized that GSK-3beta by virtue of its role in glycogen
      synthesis through the inhibition of GS will play a role in the preparation of the
      endometrium for blastocyst implantation. Immunohistochemical (IHC) analysis and
      Western blot analysis (WBA) detected GSK-3beta in the endometrium, myometrium,
      Fallopian tube and ovary. WBA showed more than 5-fold higher endometrial
      expression of the phosphorylated GSK-3beta (pGSK-3beta) isoform (inactive) in the
      secretory phase as compared with the proliferative phase (P < 0.001), whereas no
      differences in total GSK-3beta expression were detected. IHC analysis confirmed
      the WBA and showed marked expression of pGSK-3beta predominantly in glandular
      epithelial cells in early and mid secretory endometrium with scant expression
      during the proliferative phase. In in vitro experiments using human endometrial
      derived epithelial cell line (HES), progesterone did not alter total GSK mRNA or
      protein expression. However, progesterone induced a dose-dependent increase in
      the expression of pGSK-3beta, which could be blocked by RU486. Cyclic expression
      of GSK-3beta's active and inactive forms in the endometrium suggests that sex
      hormones regulate the expression of this enzyme. In vitro experiments demonstrate
      that progesterone through receptor-mediated mechanisms induces phosphorylation of
      endometrial GSK-3beta.

PMID- 16882990
TI  - Effects of mutation at the D-JH junction on affinity, specificity, and idiotypy
      of anti-progesterone antibody DB3.
AB  - The crystal structures of the Fab' fragment of the anti-progesterone monoclonal
      antibody DB3 and its complexes with steroid haptens have shown that the D-JH
      junctional residue TrpH100 is a key contributor to binding site interactions with
      ligands. The indole group of TrpH100 also undergoes a significant conformational
      change between the bound and unliganded states, effectively opening and closing
      the combining site pocket. In order to explore the effect of substitutions at
      this position on steroid recognition, we have carried out mutagenesis on a
      construct encoding a three-domain single-chain fragment (VH/K) of DB3 expressed
      in Escherichia coli. TrpH100 was replaced by 13 different amino acids or deleted,
      and the functional and antigenic properties of the mutated fragments were
      analyzed. Most substitutions, including small, hydrophobic, hydrophilic, neutral,
      and negatively charged side chains, were reduced or abolished binding to free
      progesterone, although binding to progesterone-BSA was partially retained. The
      reduction in antigen binding was paralleled by alteration of the idiotype
      associated with the DB3 combining site. In contrast, the replacement of TrpH100
      by Arg produced a mutant that retained wild-type antibody affinity and idiotype,
      but with altered specificity. Significant changes in this mutant included
      increased relative affinities of 10(4)-fold for progesterone-3-carboxymethyloxime
      and 10-fold for aetiocholanolone. Our results demonstrate an essential role for
      the junctional residue H100 in determining steroid-binding specificity and
      combining site idiotype and show that these properties can be changed by a single
      amino acid substitution at this position.

PMID- 16882989
TI  - A structural rationale for SV40 Vp1 temperature-sensitive mutants and their
      complementation.
AB  - Two groups of temperature-sensitive (ts) mutants, termed ts B and ts C, have
      mutations in the major capsid protein of SV40, Vp1. These mutants have virion
      assembly defects at the nonpermissive temperature, but can complement one another
      when two mutants, one from each group, coinfect a cell. A third group of mutants,
      termed ts BC, have related phenotypes, but do not complement other mutants. We
      found that the mutations fall into two structural and functional classes. All ts
      C and one ts BC mutations map to the region close to the Ca2+ binding sites, and
      are predicted to disrupt the insertion of the distal part of the C-terminal
      invading arm (C-arm) into the receiving clamp. They share a severe defect in
      assembly at the nonpermissive temperature, with few capsid proteins attached to
      the viral minichromosome. By contrast, all ts B and most ts BC mutations map to a
      contiguous region including acceptor sites for the proximal part of the C-arm and
      intrapentamer contacts. These mutants form assembly intermediates that carry
      substantial capsid proteins on the minichromosome. Thus, accurate virion assembly
      is prevented by mutations that disrupt interactions between the receiving
      pentamer and both the proximal and distal parts of the C-arms, with the latter
      having a greater effect. The distinct spatial localization and assembly defects
      of the two classes of mutants provide a rationale for their intracistronic
      complementation and suggest models of capsid assembly.

PMID- 16882988
TI  - Solution structure of GOPC PDZ domain and its interaction with the C-terminal
      motif of neuroligin.
AB  - GOPC (Golgi-associated PDZ and coiled-coil motif-containing protein) represents a
      PDZ domain-containing protein associated with the Golgi apparatus, which plays
      important roles in vesicular trafficking in secretory and endocytic pathways.
      GOPC interacts with many other proteins, such as the Wnt receptors Frizzled 8 and
      neuroligin via its PDZ domain. Neuroligin is a neural cell-adhesion molecule of
      the post-synapse, which binds to the presynapse molecule neurexin to form a
      heterotypic intercellular junction. Here we report the solution structure of the
      GOPC PDZ domain by NMR. Our results show that it is a canonical class I PDZ
      domain, which contains two alpha-helices and six beta-strands. Using chemical
      shift perturbation experiments, we further studied the binding properties of the
      GOPC PDZ domain with the C-terminal motif of neuroligin. The observations showed
      that the ensemble of the interaction belongs to fast exchange with low affinity.
      The 3D model of the GOPC PDZ domain/neuroligin C-terminal peptide complex was
      constructed with the aid of the molecular dynamics simulation method. Our
      discoveries provide insight into the specific interaction of the GOPC PDZ domain
      with the C-terminal peptide of Nlg and also provide a general insight about the
      possible binding mode of the interaction of Nlg with other PDZ domain-containing
      proteins.

PMID- 16882991
TI  - Peptide deformylase is a potential target for anti-Helicobacter pylori drugs:
      reverse docking, enzymatic assay, and X-ray crystallography validation.
AB  - Colonization of human stomach by the bacterium Helicobacter pylori is a major
      causative factor for gastrointestinal illnesses and gastric cancer. However, the
      discovery of anti-H. pylori agents is a difficult task due to lack of mature
      protein targets. Therefore, identifying new molecular targets for developing new
      drugs against H. pylori is obviously necessary. In this study, the in-house
      potential drug target database (PDTD, http://www.dddc.ac.cn/tarfisdock/) was
      searched by the reverse docking approach using an active natural product
      (compound 1) discovered by anti-H. pylori screening as a probe. Homology search
      revealed that, among the 15 candidates discovered by reverse docking, only
      diaminopimelate decarboxylase (DC) and peptide deformylase (PDF) have homologous
      proteins in the genome of H. pylori. Enzymatic assay demonstrated compound 1 and
      its derivative compound 2 are the potent inhibitors against H. pylori PDF (HpPDF)
      with IC50 values of 10.8 and 1.25 microM, respectively. X-ray crystal structures
      of HpPDF and the complexes of HpPDF with 1 and 2 were determined for the first
      time, indicating that these two inhibitors bind well with HpPDF binding pocket.
      All these results indicate that HpPDF is a potential target for screening new
      anti-H. pylori agents. In addition, compounds 1 and 2 were predicted to bind to
      HpPDF with relatively high selectivity, suggesting they can be used as leads for
      developing new anti-H. pylori agents. The results demonstrated that our strategy,
      reverse docking in conjunction with bioassay and structural biology, is effective
      and can be used as a complementary approach of functional genomics and chemical
      biology in target identification.

PMID- 16882992
TI  - Residue centrality, functionally important residues, and active site shape:
      analysis of enzyme and non-enzyme families.
AB  - The representation of protein structures as small-world networks facilitates the
      search for topological determinants, which may relate to functionally important
      residues. Here, we aimed to investigate the performance of residue centrality,
      viewed as a family fold characteristic, in identifying functionally important
      residues in protein families. Our study is based on 46 families, including 29
      enzyme and 17 non-enzyme families. A total of 80% of these central positions
      corresponded to active site residues or residues in direct contact with these
      sites. For enzyme families, this percentage increased to 91%, while for non
      enzyme families the percentage decreased substantially to 48%. A total of 70% of
      these central positions are located in catalytic sites in the enzyme families,
      64% are in hetero-atom binding sites in those families binding hetero-atoms, and
      only 16% belong to protein-protein interfaces in families with protein-protein
      interaction data. These differences reflect the active site shape: enzyme active
      sites locate in surface clefts, hetero-atom binding residues are in deep
      cavities, while protein-protein interactions involve a more planar configuration.
      On the other hand, not all surface cavities or clefts are comprised of central
      residues. Thus, closeness centrality identifies functionally important residues
      in enzymes. While here we focus on binding sites, we expect to identify key
      residues for the integration and transmission of the information to the rest of
      the protein, reflecting the relationship between fold and function. Residue
      centrality is more conserved than the protein sequence, emphasizing the
      robustness of protein structures.

PMID- 16882993
TI  - The refolding of different alpha-fetoprotein variants.
AB  - The effect of glycosylation on AFP foldability was investigated by parallel
      quantitative and qualitative analyses of the refolding of glycosylated and
      nonglycosylated AFP variants. Both variants were successfully refolded by
      dialysis from the denatured-reduced state, attaining comparable "refolded peak"
      profiles and refolding yields as determined by reversed-phase HPLC analysis. Both
      refolded variants also showed comparable spectroscopic fingerprints to each other
      and to their native counterparts, as determined by circular dichroism
      spectroscopy. Inclusion body-derived AFP was also readily refolded via dilution
      under the same redox conditions as dialysis refolding, showing comparable
      circular dichroism fingerprints as native nonglycosylated AFP. Quantitative
      analyses of inclusion body-derived AFP showed sensitivity of AFP aggregation to
      proteinaceous and nonproteinaceous inclusion body contaminants, where refolding
      yields increased with increasing AFP purity. All of the refolded AFP variants
      showed positive responses in ELISA that corresponded with the attainment of a
      bioactive conformation. Contrary to previous reports that the denaturation of
      cord serum AFP is an irreversible process, these results clearly show the
      reversibility of AFP denaturation when refolded under a redox-controlled
      environment, which promotes correct oxidative disulfide shuffling. The successful
      refolding of inclusion body-derived AFP suggests that fatty acid binding may not
      be required for the attainment of a rigid AFP tertiary structure, contrary to
      earlier studies. The overall results from this work demonstrate that foldability
      of the AFP molecule from its denatured-reduced state is independent of its
      starting source, the presence or absence of glycosylation and fatty acids, and
      the refolding method used (dialysis or dilution).

PMID- 16882994
TI  - A model for the coupling of alpha-helix and tertiary contact formation.
AB  - Peptides corresponding to excised alpha-helical segments of natural proteins can
      spontaneously form helices in solution. However, peptide helices are usually
      substantially less stable in solution than in the structural context of a folded
      protein, because of the additional interactions possible between helices in a
      protein. Such interactions can be thought of as coupling helix formation and
      tertiary contact formation. The relative energetic contributions of the two
      processes to the total energy of the folded state of a protein is a matter of
      current debate. To investigate this balance, an extended helix-coil model (XHC)
      that incorporates both effects has been constructed. The model treats helix
      formation with the Lifson-Roig formalism, which describes helix initiation and
      propagation through cooperative local interactions. The model postulates an
      additional parameter representing participation of a site in a tertiary contact.
      In the model, greater helix stability can be achieved through combinations of
      these short-range and long-range interactions. For instance, stronger tertiary
      contacts can compensate for helices with little intrinsic stability. By varying
      the strength of the nonlocal interactions, the model can exhibit behavior
      consistent with a variety of qualitative models describing the relative
      importance of secondary and tertiary structure. Moreover, the model is explicit
      in that it can be used to fit experimental data to individual peptide sequences,
      providing a means to quantify the two contributions on a common energetic basis.

PMID- 16882995
TI  - Fundamental processes of protein folding: measuring the energetic balance between
      helix formation and hydrophobic interactions.
AB  - Theories of protein folding often consider contributions from three fundamental
      elements: loops, hydrophobic interactions, and secondary structures. The pathway
      of protein folding, the rate of folding, and the final folded structure should be
      predictable if the energetic contributions to folding of these fundamental
      factors were properly understood. alphatalpha is a helix-turn-helix peptide that
      was developed by de novo design to provide a model system for the study of these
      important elements of protein folding. Hydrogen exchange experiments were
      performed on selectively 15N-labeled alphatalpha and used to calculate the
      stability of hydrogen bonds within the peptide. The resulting pattern of hydrogen
      bond stability was analyzed using a version of Lifson-Roig model that was
      extended to include a statistical parameter for tertiary interactions. This
      parameter, x, represents the additional statistical weight conferred upon a
      helical state by a tertiary contact. The hydrogen exchange data is most closely
      fit by the XHC model with an x parameter of 9.25. Thus the statistical weight of
      a hydrophobic tertiary contact is approximately 5.8x the statistical weight for
      helix formation by alanine. The value for the x parameter derived from this study
      should provide a basis for the understanding of the relationship between
      hydrophobic cluster formation and secondary structure formation during the early
      stages of protein folding.

PMID- 16882996
TI  - Two crystal structures of Trichoderma reesei hydrophobin HFBI--the structure of a
      protein amphiphile with and without detergent interaction.
AB  - Hydrophobins are small fungal proteins that are highly surface active and possess
      a unique ability to form amphiphilic membranes through spontaneous self-assembly.
      The first crystal structure of a hydrophobin, Trichoderma reesei HFBII, revealed
      the structural basis for the function of this amphiphilic protein--a patch
      consisting of hydrophobic side chains on the protein surface. Here, the crystal
      structures of a native and a variant T. reesei hydrophobin HFBI are presented,
      revealing the same overall structure and functional hydrophobic patch as in the
      HFBII structure. However, some structural flexibility was found in the native
      HFBI structure: The asymmetric unit contained four molecules, and, in two of
      these, an area of seven residues was displaced as compared to the two other HFBI
      molecules and the previously determined HFBII structure. This structural change
      is most probably induced by multimer formation. Both the native and the N-Cys
      variant of HFBI were crystallized in the presence of detergents, but an
      association between the protein and a detergent was only detected in the variant
      structure. There, the molecules were arranged into an extraordinary detergent
      associated octamer and the solvent content of the crystals was 75%. This study
      highlights the conservation of the fold of class II hydrophobins in spite of the
      low sequence identity and supports our previous suggestion that concealment of
      the hydrophobic surface areas of the protein is the driving force in the
      formation of multimers and monolayers in the self-assembly process.

PMID- 16882997
TI  - Crystal structure of the human TRPV2 channel ankyrin repeat domain.
AB  - TRPV channels are important polymodal integrators of noxious stimuli mediating
      thermosensation and nociception. An ankyrin repeat domain (ARD), which is a
      common protein-protein recognition domain, is conserved in the N-terminal
      intracellular domain of all TRPV channels and predicted to contain three to four
      ankyrin repeats. Here we report the first structure from the TRPV channel
      subfamily, a 1.7 A resolution crystal structure of the human TRPV2 ARD. Our
      crystal structure reveals a six ankyrin repeat stack with multiple insertions in
      each repeat generating several unique features compared with a canonical ARD. The
      surface typically used for ligand recognition, the ankyrin groove, contains
      extended loops with an exposed hydrophobic patch and a prominent kink resulting
      from a large rotational shift of the last two repeats. The TRPV2 ARD provides the
      first structural insight into a domain that coordinates nociceptive sensory
      transduction and is likely to be a prototype for other TRPV channel ARDs.

PMID- 16882998
TI  - 18F-FDG PET after radiofrequency ablation: Is timing everything?

PMID- 16882999
TI  - Targeted alpha-particle therapy of microscopic disease: Providing a further
      rationale for clinical investigation.

PMID- 16883000
TI  - 18F-FDG PET is an early predictor of pathologic tumor response to preoperative
      radiochemotherapy in locally advanced rectal cancer.
AB  - 18F-FDG PET is a useful tool for assessing the effects of chemo- or radiotherapy.
      The aim of this study was to correlate the change in tumor 18F-FDG standardized
      uptake value (SUV) during and after preoperative radiochemotherapy, with the
      pathologic response achieved in locally advanced rectal cancer (LARC) patients.
      METHODS: Thirty-three patients with LARC underwent total mesorectal excision
      after preoperative treatment, including 3 cycles of oxaliplatin, raltitrexed, 5
      fluorouracil, and folinic acid during pelvic radiotherapy (45 Gy). Staging
      procedures included endoscopic ultrasound, MRI, and CT. 18F-FDG PET scans were
      performed at baseline and 12 d after starting radiochemotherapy (intermediate) in
      all patients. Seventeen patients also had a presurgical scan. For each scan, mean
      and maximum SUVs were measured. The percentages of SUV decrease from baseline to
      intermediate (early change) and to presurgical scan (overall change) were
      assessed and correlated with pathologic response classified as tumor regression
      grade (TRG). RESULTS: Eighteen tumors (55%) showed complete (TRG1) or subtotal
      regression (TRG2) and were classified as responders, whereas 15 cases (45%; TRG3
      or TRG4) were considered nonresponders. The early median decrease of tumor SUV
      significantly differed between responders (-62%; range, -44% to -100%) and
      nonresponders (-22%; range, -2% to -48%). A significant correlation was also
      found between TRGs and early SUV changes (P < 0.0001). Responders were identified
      correctly by an early decrease of the mean SUV of > or =52%. CONCLUSION: This
      study shows that early 18F-FDG PET can predict pathologic response to
      preoperative treatment. These findings support the usefulness of (18)F-FDG PET
      during the management with radiochemotherapy of LARC patients.

PMID- 16883001
TI  - Imaging prostate cancer with 11C-choline PET/CT.
AB  - The ability of 11C-choline and multimodality fusion imaging with integrated PET
      and contrast-enhanced CT (PET/CT) was investigated to delineate prostate
      carcinoma (PCa) within the prostate and to differentiate cancer tissue from
      normal prostate, benign prostate hyperplasia, and focal chronic prostatitis.
      METHODS: All patients with PCa gave written informed consent. Twenty-six patients
      with clinical stage T1, T2, or T3 and biopsy-proven PCa underwent 11C-choline
      PET/CT after intravenous injection of 1,112 +/- 131 MBq 11C-choline, radical
      retropubic prostatovesiculectomy, and standardized prostate tissue sampling.
      Maximal standardized uptake values (SUVs) of 11C-choline within 36 segments of
      the prostate were determined. PET/CT results were correlated with histopathologic
      results, prostate-specific antigen (PSA), Gleason score, and pT stage. RESULTS:
      The SUV of 11C-choline in PCa tissue was 3.5 +/- 1.3 (mean +/- SD) and
      significantly higher than that in prostate tissue with benign histopathologic
      lesions (2.0 +/- 0.6; P < 0.001 benign histopathology vs. cancer). Visual and
      quantitative analyses of segmental 11C-choline uptake of each patient
      unambiguously located PCa in 26 of 26 patients and 25 of 26 patients,
      respectively. A threshold SUV of 2.65 yielded an area under the receiver
      operating-characteristic (ROC) curve of 0.89 +/- 0.01 for correctly locating PCa.
      The maximal 11C-choline SUV did not correlate significantly with PSA or Gleason
      score but did correlate with T stage (P = 0.01; Spearman r = 0.49). CONCLUSION:
      11C-Choline PET/CT can accurately detect and locate major areas with PCa and
      differentiate segments with PCa from those with benign hyperplasia, chronic
      prostatitis, or normal prostate tissue. The maximal tumoral 11C-choline uptake is
      related to pT stage.

PMID- 16883002
TI  - Additional value of PET/CT over PET in assessment of locoregional lymph nodes in
      thoracic esophageal squamous cell cancer.
AB  - The aim of this study was to compare the value of reviewing combined 18F-FDG
      PET/CT images with that of reviewing side-by-side PET and CT images in the
      diagnosis of locoregional lymph node metastases in patients with esophageal
      squamous cell cancer. METHODS: From November 2003 to December 2005, 45 patients
      with thoracic esophageal squamous cell cancer underwent 18F-FDG PET/CT before
      surgery. The results of reviewing combined PET/CT images and side-by-side PET and
      CT images for the diagnosis of locoregional lymph node metastases were compared
      prospectively in relation to pathologic findings. RESULTS: All patients underwent
      successful surgery, and pathologic examination confirmed nodes positive for
      metastasis in 32 patients and 82 of 397 excised nodal groups. The sensitivity,
      specificity, accuracy, positive predictive value, and negative predictive value
      of PET/CT were 93.90% (77/82 nodal groups), 92.06% (290/315), 92.44% (367/397),
      75.49% (77/102), and 98.31% (290/295), respectively, whereas those of PET were
      81.71% (67/82), 87.30% (275/315), 86.15% (342/397), 62.62% (67/107), and 94.83%
      (275/290), respectively. P values were 0.032, 0.067, 0.006, 0.063, and 0.037,
      respectively. The differences in sensitivity, accuracy, and negative predictive
      value between PET and PET/CT were statistically significant. CONCLUSION: PET/CT
      improves the sensitivity, accuracy, and negative predictive value of 18F-FDG
      imaging in the assessment of locoregional lymph nodes in thoracic esophageal
      squamous cell cancer and provides data of diagnostic significance.

PMID- 16883003
TI  - Diagnostic accuracy and prognostic value of 18F-FDG PET in Hurthle cell thyroid
      cancer patients.
AB  - Hurthle cell carcinoma is an uncommon and occasionally aggressive differentiated
      thyroid cancer associated with increased mortality compared with other
      differentiated thyroid malignancies. Because it generally has lower iodine
      avidity, 18F-FDG PET has been suggested as a more accurate imaging modality.
      However, there is limited information with regard to the true diagnostic accuracy
      and prognostic value of 18F-FDG PET in this disease. METHODS: All patients with
      Hurthle cell thyroid cancer who underwent their first 18F-FDG PET scan between
      May 1996 and February 2003 were identified retrospectively. 18F-FDG PET scans
      were reviewed and compared with all available imaging studies, including CT,
      ultrasound, and radioiodine scintigraphy (RIS). Abnormal 18F-FDG uptake was
      assessed visually and by measuring the maximum standardized uptake value (SUVmax)
      of the most intense lesion. Clinical follow-up for at least 1 y or until death
      was required for inclusion. RESULTS: Forty-four patients met inclusion criteria.
      The median follow-up was 2.9 y. There were 24 positive and 20 negative 18F-FDG
      PET scans with 1 false-positive and 1 false-negative study, resulting in a
      diagnostic sensitivity of 95.8% and a specificity of 95%. In 5 of 11 patients who
      had both positive CT and 18F-FDG PET findings, 18F-FDG PET revealed additional
      sites of disease. Furthermore, 18F-FDG PET correctly classified as negative 3
      patients with false-positive CT findings. In 3 of 6 patients with positive RIS,
      18F-FDG PET revealed additional sites of metastatic disease. Ten patients with
      positive 18F-FDG PET had negative RIS. Only 1 patient with negative 18F-FDG PET
      had positive RIS. The SUVmax also provided prognostic information: In a stepwise
      fashion, each increase in intensity by SUVmax unit was associated with a 6%
      increase in mortality (P < 0.001). The 5-y overall survival in patients with
      SUVmax < 10 was 92%; it declined to 64% in those with SUVmax > 10 (P < 0.01).
      CONCLUSION: 18F-FDG PET has excellent diagnostic accuracy in Hurthle cell thyroid
      cancer patients, improving on CT and RIS. Intense 18F-FDG uptake in lesions is an
      indicator of a poor prognosis. Our data suggest that all patients with Hurthle
      cell thyroid cancer should undergo 18F-FDG PET as part of their initial
      postoperative staging and periodically to screen for occult recurrence,
      particularly in patients with elevated serum thyroglobulin.

PMID- 16883004
TI  - Detection of Richter's transformation of chronic lymphocytic leukemia by PET/CT.
AB  - Our objective was to evaluate the accuracy of PET/CT for the diagnosis of
      Richter's transformation of chronic lymphocytic leukemia (CLL) to diffuse large
      cell lymphoma. METHODS: A retrospective study was performed of 37 patients with
      CLL who underwent 18F-FDG PET/CT at our institution between March 2003 and July
      2005. All PET/CT scans were reviewed in consensus by 2 diagnostic radiologists.
      Sites of abnormal 18F-FDG uptake with a maximum standardized uptake value
      (SUVmax) of greater than 5 were considered highly suggestive of Richter's
      transformation. The PET/CT findings were correlated with histologic findings from
      bone marrow or lymph node biopsy performed within 6 wk of PET/CT and with
      clinical follow-up. RESULTS: The 37 patients (26 men and 11 women; mean age, 61
      y, range, 40-82 y) underwent 57 PET/CT scans. In 10 (91%) of 11 patients with
      Richter's transformation, PET/CT detected sites of abnormal 18F-FDG uptake having
      an SUVmax of greater than 5. Richter's transformation was missed in 1 patient who
      had only low-grade 18F-FDG uptake (SUVmax < 5). Nine patients had false-positive
      PET/CT findings; in 3 of these patients, alternative malignancies were diagnosed
      (Hodgkin's disease; metastatic neuroendocrine carcinoma; non-small cell lung
      cancer). In all remaining patients, PET/CT correctly excluded Richter's
      transformation. For the specific diagnosis of Richter's transformation of CLL to
      diffuse large B-cell lymphoma, PET/CT had overall sensitivity, specificity, and
      positive and negative predictive values of 91%, 80%, and 53% and 97%,
      respectively. CONCLUSION: PET/CT can detect Richter's transformation of CLL to
      diffuse large B-cell lymphoma with a high sensitivity and a high negative
      predictive value.

PMID- 16883005
TI  - Increased 18F-FDG uptake in degenerative disease of the spine: Characterization
      with 18F-FDG PET/CT.
AB  - We determined the prevalence of abnormal spinal 18F-FDG uptake and assessed the
      relationship between the severity of findings on 18F-FDG PET and the severity of
      degenerative spinal disease (DSD) on CT. METHODS: PET/CT scans of 150 patients
      >18 y old, referred for whole-body 18F-FDG PET/CT for evaluation of known or
      suspected malignancy from June to July 2002, were analyzed retrospectively for
      the presence of increased 18F-FDG uptake in the spine and for anatomic
      correlates. Initially, PET images were examined and foci of 18F-FDG uptake in the
      spine were graded on a 0-4 scale based on intensity of 18F-FDG uptake (0 =
      definitely normal, 1 = probably normal, 2 = equivocal, 3 = probably abnormal, 4 =
      definitely abnormal). From PET alone, an impression as to whether lesions were
      most likely metastases or degenerative, as well the level of the spine involved,
      was also recorded. CT images of all 150 patients were reviewed independently by a
      musculoskeletal radiologist, who was unaware of patient identification, history,
      and findings of other imaging modalities, with the location recorded and severity
      graded on a 4-point-scale (0 = normal, 1 = mild, 2 = moderate, 3 = severe for
      both degenerative disk and facet disease). The relationship between PET and CT
      findings was then determined. RESULTS: Of the 150 patients, 63 (42.0%) had no
      abnormal findings in the spine on PET (grade 0), 27 (18.0%) had grade 1, 25
      (16.7%) had grade 2, 17 (11.3%) had grade 3, and 16 patients (10.7%) had grade 4
      18F-FDG uptake for DSD. Two additional patients had apparent spinal metastases
      with no degenerative changes. Five patients had metastases and DSD (included
      above). Of the patients who had abnormal spinal findings graded as probable or
      definite for DSD on CT (grades 3-4), 11 had abnormal findings in the cervical
      spine, 16 in the thoracic spine, and 23 patients in the lumbosacral spine. Seven
      patients (4.7%) had PET findings suggestive of spinal metastases. For patients
      with a maximum regional DSD score of 3, the mean 18F-FDG uptake for that spinal
      level was 1.4 +/- 1.5, whereas for patients with a maximum regional DSD score of
      0, the mean PET grade was significantly lower at 0.4 +/- 0.9 (P = 0.0001).
      CONCLUSION: Incidental findings on PET suggestive of DSD are common (22% of
      patients), most common in the lumbosacral spine, and can be recognized on CT. The
      severity of PET findings correlates with the severity of degenerative disk and
      facet disease as graded by CT, likely due to the fact that the inflammatory
      process that accompanies DSD is evident on PET. Increased 18F-FDG uptake in DSD
      should not be confused with metastatic disease.

PMID- 16883006
TI  - Increased uptake of 111In-octreotide in idiopathic pulmonary fibrosis.
AB  - Idiopathic pulmonary fibrosis (IPF) is characterized by an uncontrolled
      accumulation and activation of lung fibroblasts. A modulation of fibroblast
      activation has been observed in various systems with octreotide, a synthetic
      somatostatin analog with strong affinity for the somatostatin receptor subtype 2
      (sst2). One aim of our study was to evaluate the expression of somatostatin
      receptors in the lungs of patients with IPF. A second aim was to evaluate the
      relationship between 111In-octreotide uptake and the effect of pulmonary fibrosis
      as assessed by lung function tests and parameters and by radiologic findings.
      METHODS: We investigated 11 patients with IPF, 6 patients with pulmonary fibrosis
      associated with systemic sclerosis (SSc), and 19 patients with disease not of the
      lung (control patients). The expression of somatostatin receptors was evaluated
      in vivo using 111In-octreotide scintigraphy. We evaluated the relationship
      between 111In-octreotide uptake and the activity of pulmonary fibrosis as
      assessed by lung function tests, bronchoalveolar lavage (BAL) cellularity, and
      high-resolution CT (HRCT) of the chest. Planar images and thoracic SPECT (24 h)
      were performed after injection of 222 MBq of 111In-octreotide. Lung uptake was
      quantified using the lung-to-background ratio (L/B). In addition, the expression
      of sst2 was evaluated in vitro, in frozen lung-tissue samples using
      autoradiography, and in human cultures of lung fibroblasts using a ligand-binding
      assay. RESULTS: Compared with lung uptake in control patients (median L/B, 1.25;
      range, 1.14-1.49), lung uptake was increased in all 11 IPF patients (median L/B,
      2.63; range, 1.59-3.13; P < 0.001) and in 4 of 6 SSc patients (median L/B, 1.68;
      range, 1.42-2.16). The L/B was lower in SSc patients than in IPF patients (P =
      0.011). Increased uptake correlated with the alteration of lung function (carbon
      monoxide diffusing capacity [rho = -0.655; P = 0.038], diffusing capacity for
      carbon monoxide and alveolar volume ratio [rho = -0.627; P = 0.047], vital
      capacity [rho = -0.609; P = 0.054], and total lung capacity [rho = -0.598; P =
      0.058]) and with the intensity of alveolitis (total BAL cellularity [rho = 0.756;
      P = 0.045], neutrophil counts [rho = 0.738; P = 0.05]), and HRCT fibrosis score
      (rho = 0.673; P = 0.007). Autoradiography suggested that vascular structures were
      a prominent binding site. Lung fibroblasts expressed somatostatin receptors in
      vitro as measured by binding assay. CONCLUSION: Our preliminary results
      identified an increased expression of sst2 in (mainly idiopathic) pulmonary
      fibrosis. Lung uptake correlates with the alteration of lung function and with
      the intensity of alveolitis.

PMID- 16883007
TI  - Comparison of 64-slice CT with gated SPECT for evaluation of left ventricular
      function.
AB  - Precise and reliable assessment of left ventricular (LV) function and dimensions
      is prognostically important in cardiac patients. As the integration of SPECT and
      multislice CT into hybrid scanners will promote the combined use of both
      techniques in the same patient, a comparison of the 2 methods is pertinent. We
      aimed at comparing LV dimensions, muscle mass, and function obtained by
      electrocardiographically gated 64-slice CT versus gated-SPECT. METHODS: Sixty
      patients (mean age, 64 +/- 8 y) referred for evaluation of coronary artery
      disease underwent 99mTc-tetrofosmin gated SPECT and 64-slice CT within 4 +/- 2 d.
      LV ejection fraction (LVEF), end-systolic volume (ESV), and end-diastolic volume
      (EDV) from CT were compared with SPECT. Additionally, LV muscle mass and
      quantitative regional wall motion were assessed in 20 patients with both methods.
      RESULTS: CT was in good agreement with SPECT for quantification of LVEF (r =
      0.825), EDV (r = 0.898), and ESV (r = 0.956; all P < 0.0001). LVEF was 59% +/-
      13% measured by SPECT and slightly higher but not significantly different by CT
      (60% +/- 12%; mean difference compared with SPECT, 1.1% +/- 1.7%; P = not
      significant). A systematic overestimation using CT for EDV (147 +/- 60 mL vs. 113
      +/- 52 mL; mean difference, 33.5 +/- 23.1 mL) and ESV (63 +/- 55 mL vs. 53 +/- 49
      mL; mean difference, 9.3 +/- 15.9 mL; P < 0.0001) was found compared with SPECT.
      A good correlation for muscle mass was found between the 2 methods (r = 0.868; P
      < 0.005). However, muscle mass calculated by SPECT was significantly lower
      compared with CT (127 +/- 24 g vs. 148 +/- 37 g; mean difference, 23.0 +/- 12.2
      g; P < 0.001). The correlation for regional wall motion between the 2 methods was
      moderate (r = 0.648; P < 0.0001). CONCLUSION: LVEF and LV functional parameters
      as determined by 64-slice CT agree over a wide range of clinically relevant
      values with gated SPECT. However, interchangeable use of the 2 techniques should
      be avoided for LV volumes, muscle mass, and regional wall motion because of
      variances inherent to the different techniques.

PMID- 16883008
TI  - Tissue distribution of 18F-FDG-labeled peripheral hematopoietic stem cells after
      intracoronary administration in patients with myocardial infarction.
AB  - Adult stem cell therapy is expected to improve left ventricular function in
      patients with myocardial infarction. Because of the low risk of arrhythmia and
      the maximal concentration at the target tissue, intracoronary infusion of stem
      cells is preferred. The aim of this study was to investigate the homing and
      tissue distribution of intracoronary injected peripheral hematopoietic stem cells
      labeled with 18F-FDG. METHODS: Seventeen patients with myocardial infarction were
      included as the intracoronary injection group (14 males, 3 females; age, 58 +/-
      12 y). Three patients underwent intravenous stem cell injection as the
      intravenous injection group (3 males, 0 females; age, 50 +/- 20 y). After
      mobilization with granulocyte colony-stimulating factor (G-CSF), peripheral stem
      cells were collected by means of apheresis. 18F-FDG labeling of stem cells was
      performed for 40 min with gentle intermittent mixing at 37 degrees C. The mean
      labeling efficiency was 72% (range, 46%-95%), and 44.4-175 MBq (1.2-5 mCi) of 18F
      FDG-labeled stem cells were injected via an intracoronary catheter after stenting
      in infarct-related arteries. PET/CT images were obtained with a 3-dimensional
      acquisition mode 2 h after intracoronary infusion. RESULTS: Two hours after
      intracoronary infusion, 1.5% (range, 0.2%-3.3%) of injected stem cells
      accumulated at the infarcted myocardium. Outside of the myocardium, spleen,
      liver, bladder, and bone marrow showed a high stem cell accumulation. The delayed
      image of a patient up to 20 h showed a prolonged residence of stem cells at the
      myocardium. Intravenous injection of stem cells showed a high initial lung uptake
      with no myocardial activity. CONCLUSION: We have shown that 18F-FDG-labeled stem
      cell PET could be used to assess the tissue distribution and to measure the
      amount of stem cells at a target tissue. 18F-FDG-labeled stem cell PET can be
      used to measure and optimize the amount of stem cells injected.

PMID- 16883009
TI  - Prognostic stratification of obese patients by stress 99mTc-tetrofosmin
      myocardial perfusion imaging.
AB  - Obesity is a major heath problem associated with increased cardiovascular
      mortality. There are currently no data to support a role for stress imaging
      techniques in the risk stratification of obese patients. The aim of this study
      was to assess the independent value of stress 99mTc-tetrofosmin SPECT in
      predicting mortality and hard cardiac events in obese patients. METHODS: We
      studied 265 patients with a body mass index greater than 30 kg/m2 by exercise or
      dobutamine stress 99mTc-tetrofosmin myocardial perfusion tomography. Endpoints
      during follow-up were cardiac death and death of any cause. RESULTS: The mean
      patient age (+/-SD) was 59 +/- 10 y, and 110 of the patients were men (42%). The
      mean body mass index was 37 +/- 7 kg/m2. Scan findings were normal in 113
      patients (43%). Myocardial perfusion abnormalities were fixed in 62 patients
      (23%) and reversible in 90 patients (34%). During a mean follow-up period of 5.5
      +/- 2 y, 41 patients (15%) died. Death was considered cardiac in 22 patients
      (8%). Nonfatal myocardial infarction occurred in 20 patients (7.5%). The annual
      cardiac death rate was 0.6% in patients with normal perfusion and 3.3% in
      patients with abnormal perfusion. Patients with a multiple-vessel distribution of
      abnormalities had a higher cardiac death rate than did patients with a single
      vessel distribution (4.1% vs. 2.5%, P < 0.05). The annual mortality rate was 1.3%
      in patients with normal perfusion and 4.2% in patients with abnormal perfusion.
      In a multivariate analysis, perfusion abnormalities were independently predictive
      of cardiac mortality (risk ratio, 3.2; 95% confidence interval, 1.5-6.7) and
      overall mortality (risk ratio, 2.7; 95% confidence interval, 1.4-4.3).
      CONCLUSION: Stress 99mTc-tetrofosmin myocardial perfusion imaging is a useful
      tool for predicting cardiac and overall mortality in obese patients.

PMID- 16883010
TI  - Nitrate administration increases blood flow in dysfunctional but viable
      myocardium, leading to improved assessment of myocardial viability: A PET study.
AB  - SPECT with 99mTc-labeled agents is better able to detect viability after nitrate
      administration. Nitrates induce vasodilation and may increase blood flow to
      severely hypoperfused but viable myocardium, thereby enhancing tracer delivery
      and improving the detection of viability. Quantitative data on the changes in
      blood flow are lacking in SPECT but can be provided by PET. The aim of the
      present study was to use PET to evaluate whether nitrate administration increases
      blood flow to chronically dysfunctional but viable myocardium. METHODS: 13N
      Ammonia PET was used to quantitatively assess blood flow, and 18F-FDG PET was
      used as the gold standard to detect viable myocardium. Twenty-five patients with
      chronic ischemic left ventricular dysfunction underwent 13N-ammonia PET at rest
      and after nitrate administration. RESULTS: A significant increase in nitrate
      enhanced blood flow was observed in viable segments (from 0.55 +/- 0.15 to 0.68
      +/- 0.24 mL/min/g, P < 0.05). No statistically significant change in blood flow
      was observed in nonviable segments (0.60 +/- 0.20 vs. 0.55 +/- 0.18 mL/min/g). A
      ratio of at least 1.1 for nitrate-enhanced flow to resting flow allowed optimal
      detection of viable myocardium, yielding a sensitivity of 82% with a specificity
      of 100%. CONCLUSION: 13N-Ammonia PET showed a significant increase in nitrate
      enhanced blood flow in viable myocardium, whereas blood flow remained unchanged
      after nitrate administration in nonviable myocardium. Nitrate use during
      myocardial perfusion imaging will lead to improved assessment of myocardial
      viability.

PMID- 16883011
TI  - Clinically significant abnormal findings on the "nondiagnostic" CT portion of low
      amperage-CT attenuation-corrected myocardial perfusion SPECT/CT studies.
AB  - Attenuation correction is recommended to optimize the performance of cardiac
      SPECT. The 2.5-mA CT commonly used for this purpose in myocardial perfusion SPECT
      is generally considered "nondiagnostic" in quality. In other areas of cardiac and
      hybrid imaging, diagnostically relevant abnormal findings on higher-quality CT
      studies have been described. The purpose of this study was to establish the
      frequency and significance of abnormal findings on low-amperage-CT cardiac
      SPECT/CT scans and to assess whether a systematic review of the nondiagnostic CT
      findings should be recommended. METHODS: Two hundred consecutive patients who
      underwent clinical low-amperage-CT attenuation-corrected myocardial perfusion
      studies acquired on a SPECT/CT system were included in the study. The cardiac CT
      images were reviewed in consensus by both an experienced CT reader and a nuclear
      medicine resident less experienced in CT. Abnormal CT findings of varying
      significance were recorded. RESULTS: Eighty-one patients had no abnormal CT
      findings. In the remaining 119 patients, 234 abnormalities were detected. Twenty
      five major findings (in 21 patients) were seen, and 16 of these had been
      previously unrecognized. Sixty-four minor and 131 minimal findings were noted.
      Fourteen findings were labeled as equivocal (i.e., the CT findings were not
      definite). CONCLUSION: Potentially significant abnormal findings on the
      nondiagnostic-CT portion of the cardiac SPECT/CT examination were detected in
      10.5% of our patients. These data suggest that, in addition to the review of the
      emission image dataset, low-amperage-CT findings should routinely be assessed for
      major diagnostic abnormalities.

PMID- 16883012
TI  - Response-dependent differences in regional cerebral blood flow changes with
      citalopram in treatment of major depression.
AB  - Major depression (MD) is the most frequent psychiatric disorder with a predicted
      increase within the next decade. The understanding of the neurobiologic basis of
      its cause, antidepressive treatment effects, and identification of treatment
      outcome predictors is of crucial importance to warrant efficient medical care.
      The aim of our study was to investigate differences of regional cerebral blood
      flow (rCBF) in MD between responders and nonresponders in the beginning and
      differences during the course of treatment. METHODS: 99mTc-Labeled d,l
      hexamethylpropyleneamine oxime brain scans under resting conditions were
      performed on 65 patients with MD. All patients were treated with citalopram as an
      antidepressive monotherapy. SPECT scans were performed 2 times, at the beginning
      (t1) and after 4 wk of medication (t2). Voxel-by-voxel analyses were performed
      using SPM. Unpaired t test, paired t test, and multigroup analysis were used on a
      significance threshold of P < 0.005 (uncorrected) to identify significant
      differences in rCBF between responders and nonresponders at t1, within both
      groups over time of treatment (t2-t1), as well as a group x time interactions.
      RESULTS: Thirty-five patients responded after 4 wk of treatment. Distinct
      differences between responders and nonresponders were found at the beginning of
      treatment and also relating to changes in rCBF during treatment. Responders
      showed a higher posterior cingulate activity at t1. Furthermore, an opposite
      direction of rCBF changes during treatment could be observed in this area.
      CONCLUSION: The differences in rCBF in responders and nonresponders in the
      posterior cingulate at t1 and the opposite directed changes in rCBF in both
      groups during treatment in this region suggest that the posterior cingulate
      function plays a key role in the pathophysiology of depression and may have a
      predictive value for antidepressive treatment outcome.

PMID- 16883013
TI  - The role of PET in lymphoma.
AB  - Malignant lymphomas are a heterogeneous group of diseases whose treatment and
      prognosis depend on accurate staging and evaluation of histologic features. The
      conventional imaging procedure is CT; however, nuclear medicine imaging has also
      had a prominent role. Single-photon imaging with 67Ga-citrate has been widely
      used for lymphomas. PET with 18F-FDG has gained a role in the staging and follow
      up of lymphomas, largely replacing gallium as the nuclear medicine study of
      choice. 18F-FDG PET has proved useful in the staging and follow-up of Hodgkin's
      disease and non-Hodgkin's lymphoma (especially more aggressive types), and the
      widespread use of PET/CT has also increased the sensitivity and specificity. Its
      usefulness for the staging of slow-growing lymphomas has not been established.
      After the basics of staging and classification of lymphomas have been outlined,
      this article will review the role of 18F-FDG PET in the management of patients
      with lymphoma. PET tracers other than (18)F-FDG, such as positron-emitting
      isotopes of gallium and the cellular proliferation marker 18F-3'-deoxy-3'
      fluorothymidine, will be discussed and future directions for PET in lymphoma
      proposed.

PMID- 16883014
TI  - Anti-CD45 monoclonal antibody YAML568: A promising radioimmunoconjugate for
      targeted therapy of acute leukemia.
AB  - The outcome of hematopoietic cell transplantation for hematologic malignancies
      may be improved by delivering targeted radiation to hematopoietic organs while
      relatively sparing nontarget organs. We evaluated the biodistribution of 111In
      labeled anti-CD45 antibody in humans using the rat IgG2a monoclonal antibody
      YAML568 that recognizes a common CD45 epitope present on all human leukocytes.
      METHODS: Eight patients undergoing bone marrow transplantation received YAML568
      labeled with 122 +/- 16 MBq of 111In intravenously followed by serial blood
      sampling, urine collection, and conjugated view planar gamma-camera imaging up to
      144 h after injection. Time-activity curves were obtained using region-of
      interest analysis in the accumulating organs and residence times were calculated.
      An estimate for the radiation-absorbed doses for each organ per unit of
      administered activity of 90Y was calculated using software for internal dose
      assessment. The first patient received no unlabeled antibody preloading. The
      second 2 patients received a preloading dose of 10 mg (0.15 mg/kg). The last 5
      patients received a preloading dose of 30-47 mg (0.5 mg/kg). RESULTS: No
      significant administration-related side effects were seen. The 3 patients
      receiving no antibody or low antibody preloading had an unfavorable
      biodistribution with a high initial accumulation of activity in the liver (37%)
      and the spleen (34%). For the patients receiving 0.5-mg/kg antibody preloading,
      the estimated radiation-absorbed doses for red bone marrow, spleen, liver,
      kidney, and total body were 6.4 +/- 1.2, 19 +/- 5, 3.9 +/- 1.4, 1.1 +/- 0.4, and
      0.6 +/- 0.1 mGy/MBq, respectively, demonstrating preferential red marrow
      targeting. A linear regression model showed that the amount of unlabeled antibody
      preloading per body weight has a strong influence on the estimated red marrow
      absorbed dose (P = 0.003, R2 = 0.80). CONCLUSION: This study shows that the anti
      CD45 monoclonal antibody YAML568 is suitable for delivering selectively radiation
      to hematopoietic tissues when labeled with 90Y provided that a preloading dose of
      about 0.5 mg/kg unlabeled antibody is given.

PMID- 16883015
TI  - Alpha-radioimmunotherapy of intraperitoneally growing OVCAR-3 tumors of variable
      dimensions: Outcome related to measured tumor size and mean absorbed dose.
AB  - The purpose of this work was to (a) investigate the efficacy of
      radioimmunotherapy using 211At-MX35 F(ab')2 or 211At-Rituximab F(ab')2
      (nonspecific antibody) against differently advanced ovarian cancer in mice; (b)
      image the tumor growth on the peritoneum; and (c) calculate the specific energy
      and mean absorbed dose to tumors and critical organs. METHODS: Two experiments
      with 5-wk-old nude mice (n = 100 + 93), intraperitoneally inoculated with
      approximately 1 x 10(7) NIH:OVCAR-3 cells, were done. At either 1, 3, 4, 5, or 7
      wk after inoculation animals were intraperitoneally treated with approximately
      400 kBq 211At-MX35 F(ab')2 (n = 50 + 45), approximately 400 kBq 211At-Rituximab
      F(ab')2 (n = 25 + 24), or unlabeled Rituximab F(ab')2 (n = 25 + 24). At the time
      of treatment 29 animals were sacrificed and biopsies were taken for determination
      of tumor sizes using scanning electron microscopy (SEM). Eight weeks after each
      treatment the animals were sacrificed and the presence of macro- and microscopic
      tumors and ascites was determined. The specific energy and mean absorbed dose to
      tumors were calculated. The activity concentration was measured in critical
      organs and abdominal fluid. RESULTS: When given treatment 1, 3, 4, 5, or 7 wk
      after cell inoculation the tumor-free fraction (TFF) was 95%, 68%, 58%, 47%, 26%,
      and 100%, 80%, 20%, 20%, and 0% when treated with 211At-MX35 F(ab')2 or 211At
      Rituximab F(ab')2, respectively. The SEM images revealed maximum tumor radius of
      approximately 30 mum 1 wk after cell inoculation, increasing to approximately 340
      mum at 7 wk. Specific energy to cell nuclei varied between 0 and approximately
      540 Gy, depending on assumptions regarding activity distribution and tumor size.
      The mean absorbed dose to thyroid, kidneys, and bone marrow was approximately 35,
      approximately 4, and approximately 0.3 Gy, respectively. CONCLUSION: Treatment
      with 211At-MX35 F(ab')2 or 211At-Rituximab F(ab')2 resulted in a TFF of 95%-100%
      when the tumor radius was < or =30 microm. The TFF was decreased (TFF < or = 20%)
      for 211At-Rituximab F(ab')2 when the tumor radius exceeded the range of the alpha
      particles. The specific antibody gave for these tumor sizes a significantly
      better TFF, explained by a high mean absorbed dose (>22 Gy) from the activity
      bound to the tumor surface and probably some contribution from penetrating
      activity.

PMID- 16883016
TI  - 18F-FDG small-animal PET for monitoring the therapeutic effect of CT-guided
      radiofrequency ablation on implanted VX2 lung tumors in rabbits.
AB  - The primary goals of this study were to investigate the behavior of normal lung
      tissues after radiofrequency ablation (RFA) and to determine the suitability of
      18F-FDG PET, using a dedicated small-animal scanner, for monitoring the early
      therapeutic effects of RFA on VX2 lung tumors (VX2s) in rabbits. METHODS:
      Fourteen Japanese white rabbits with normal lungs underwent RFA, followed by 18F
      FDG PET at 1 d and at 1, 2, 4, and 8 wk. In addition, 7 rabbits with untreated
      VX2s underwent 18F-FDG PET, and 13 rabbits with RFA-treated VX2s underwent 18F
      FDG PET at 1 d (n = 7) or 1 wk (n = 6) after the treatment. RESULTS: After RFA of
      normal lungs, ring-shaped accumulations of 18F-FDG, which coincided with
      inflammation caused by ablation, were observed. The mean early- (40-60 min after
      injection) and delayed (100-120 min)-phase ablated lesion-to-muscle ratios were,
      respectively, 2.9 +/- 1.0 and 3.3 +/- 0.8 (1 d), 4.1 +/- 0.6 and 5.2 +/- 0.9 (1
      wk), 4.1 +/- 1.0 and 5.3 +/- 1.5 (2 wk), 3.1 +/- 0.5 and 3.6 +/- 1.1 (4 wk), and
      1.8 +/- 0.1 and 2.3 +/- 0.1 (8 wk). At 4 and 8 wk, the uptake was less than that
      at 1 and 2 wk (P < 0.05). VX2s showed mean tumor-to-muscle ratios of 6.6 +/- 2.1
      and 8.6 +/- 3.3 at the early and delayed phases, respectively. For ablated
      tumors, the respective ratios were 0.8 +/- 0.4 and 1.1 +/- 0.7 (1 d) and 1.2 +/-
      0.5 and 1.5 +/- 0.7 (1 wk). These values were significantly lower than those for
      nonablated tumors (P < 0.001). Histopathologic examination confirmed the absence
      of viable tumors. 18F-FDG accumulation around ablated tumors reflected thermally
      damaged normal tissues and was significantly lower than that of control VX2s (P <
      0.01). CONCLUSION: Our data suggest that 18F-FDG PET is promising for evaluating
      the therapeutic response of lung malignancies to RFA: Accumulation of 18F-FDG in
      surrounding normal tissues appears to be time dependent, and the data suggest
      that, clinically, 18F-FDG PET should be performed 4 wk or more after RFA. Delayed
      phase images seem to better distinguish tumor from inflammation than do early
      phase images.

PMID- 16883017
TI  - Characterization of uptake of the new PET imaging compound 18F-fluorobenzyl
      triphenyl phosphonium in dog myocardium.
AB  - 18F-Labeled p-fluorobenzyl triphenyl phosphonium cation (18F-FBnTP) is a member
      of a new class of positron-emitting lipophilic cations that may act as myocardial
      perfusion PET tracers. Here, we characterize the 18F-FBnTP uptake and retention
      kinetics, in vitro and in vivo, as well as the myocardial and whole-body
      biodistribution in healthy dogs, using PET. METHODS: Time-dependent accumulation
      and retention of 18F-FBnTP in myocytes in vitro was studied. Seven anesthetized,
      mongrel dogs underwent dynamic PET scans of the heart after intravenous
      administration of 126-240 MBq 18F-FBnTP. In 4 of the 7 dogs, at the completion of
      a 60-min dynamic scan, whole-body scans (4 bed positions, 5-min emission and 3
      min transmission per bed) were acquired. Arterial blood samples were collected at
      0, 5, 10, 20, 30, and 60 min after administration, plasma activity was counted,
      and high-performance liquid chromatographic analyses for metabolites were
      performed. The extent of defluorination was assessed by measuring 18F-FBnTP bone
      uptake in mice, compared with 18F-fluoride. RESULTS: The metabolite fraction
      comprised <5% of total activity in blood at 5 min and gradually increased to 25%
      at 30 min after injection. In vivo, 18F-FBnTP myocardial concentration reached a
      plateau level within a few minutes, which was retained throughout the scanning
      time. In contrast, activity in the blood pool and lungs cleared rapidly (half
      life = 19.5 +/- 4.4 and 30.7 +/- 11.6 s, respectively). Liver uptake did not
      exceed the activity measured in the myocardium. At 60 min, the uptake ratios of
      left ventricular wall to blood, lung, and liver (mean of 7 dogs) were 16.6, 12.2,
      and 1.2, respectively. Summation of activity from 5 to 15 min and from 30 to 60
      min after injection produced high-quality cardiac images of similar contrast.
      Circumferential sampling and a polar plot revealed a uniform distribution, near
      unitary value, throughout the entire myocardium. The mean coefficient of
      variance, on 30- to 60-min images along the septum-to-anterior wall and the apex
      to-base axes was 7.58% +/- 1.04% and 6.11% +/- 0.89% (mean +/- SD; n = 7),
      respectively, and on 5- to 15-min images was 7.25% +/- 1.43% and 6.12% +/- 1.88%,
      respectively. 18F-FBnTP whole-body distribution was highly organ specific with
      the kidney cortex being the major target organ, followed by the heart and the
      liver. CONCLUSION: 18F-FBnTP is a promising new radionuclide for cardiac imaging
      using PET with rapid kinetics, uniform myocardial distribution, and favorable
      organ biodistribution.

PMID- 16883018
TI  - 99mTc-labeled C2A domain of synaptotagmin I as a target-specific molecular probe
      for noninvasive imaging of acute myocardial infarction.
AB  - The exposure of phosphatidylserine (PtdS) is a common molecular marker for both
      apoptosis and necrosis and enables the simultaneous detection of these distinct
      modes of cell death. Our aim was to develop a radiotracer based on the PtdS
      binding activity of the C2A domain of synaptotagmin I and assess 99mTc-C2A-GST
      (GST is glutathione S-transferase) using a reperfused acute myocardial infarction
      (AMI) rat model. METHODS: The binding of C2A-GST toward apoptosis and necrosis
      was validated in vitro. After labeling with 99mTc via 2-iminothiolane thiolation,
      radiochemical purity and radiostability were tested. Pharmacokinetics and
      biodistribution were studied in healthy rats. The uptake of 99mTc-C2A-GST within
      the area at risk was quantified by direct gamma-counting, whereas nonspecific
      accumulation was estimated using inactivated 99mTc-C2A-GST. In vivo planar
      imaging of AMI in rats was performed on a gamma-camera using a parallel-hole
      collimator. Radioactivity uptake was investigated by region-of-interest analysis,
      and postmortem tetrazolium staining versus autoradiography. RESULTS:
      Fluorescently labeled and radiolabeled C2A-GST bound both apoptotic and necrotic
      cells. 99mTc-C2A-GST had a radiochemical purity of >98% and remained stable.
      After intravenous injection, the uptake in the liver and kidneys was significant.
      For 99mTc-C2A-GST, radioactivity uptake in the area at risk reached between 2.40
      and 2.63 %ID/g (%ID/g is percentage injected dose per gram) within 30 min and
      remained plateaued for at least 3 h. In comparison, with the inactivated tracer
      the radioactivity reached 1.06 +/- 0.49 %ID/g at 30 min, followed by washout to
      0.52 +/- 0.23 %ID/g. In 7 of 7 rats, the infarct was clearly identifiable as
      focal uptake in planar images. At 3 h after injection, the infarct-to-lung ratios
      were 2.48 +/- 0.27, 1.29 +/- 0.09, and 1.46 +/- 0.04 for acute-infarct rats with
      (99m)Tc-C2A-GST, sham-operated rats with (99m)Tc-C2A-GST, and acute-infarct rats
      with 99mTc-C2A-GST-NHS (NHS is N-hydroxy succinimide), respectively. The
      distribution of radioactivity was confirmed by autoradiography and histology.
      CONCLUSION: The C2A domain of synaptotagmin I labeled with fluorochromes or a
      radioisotope binds to both apoptotic and necrotic cells. Ex vivo and in vivo data
      indicate that, because of elevated vascular permeability, both specific binding
      and passive leakage contribute to the accumulation of the radiotracer in the area
      at risk. However, the latter component alone is insufficient to achieve
      detectable target-to-background ratios with in vivo planar imaging.

PMID- 16883019
TI  - Acquisition settings for PET of 124I administered simultaneously with therapeutic
      amounts of 131I.
AB  - Radiation dosimetry of thyroid cancer therapy with 131I can be performed by
      coadministration of 124I followed by longitudinal PET scans over several days.
      The photons emitted by 131I may affect PET image quality. The aim of this study
      was to assess the influence of large amounts of 131I on PET image quality and
      accuracy with various acquisition settings. METHODS: Noise equivalent count (NEC)
      rates of 124I only were measured with a standard clinical PET scanner. Apart from
      the standard 350- to 650-keV energy window, 425- to 650-keV and 460- to 562-keV
      windows were used and data were acquired both with (2-dimensional) and without (3
      dimensional [3D]) septa. A phantom containing 6 hot spheres, filled with a
      combination of 131I and 124I and with a sphere-to-background ratio of 18:1, was
      scanned repeatedly with energy window settings as indicated and emission and
      transmission scan durations of 7 and 3 min, respectively. NEC rates were
      calculated and compared with those measured with the phantom filled with only
      124I. Sphere-to-background ratios in the reconstructed images were determined.
      One patient with known metastatic thyroid cancer was scanned using energy window
      settings and scan times as indicated 3 and 6 d after administration of 5.5 GBq of
      131I and 75 MBq of 124I. RESULTS: The highest 124I-only NEC rates were obtained
      using a 425- to 650-keV energy window in 3D mode. In the presence of (131)I, the
      settings giving the highest NEC rate and contrast were 425-650 keV and 460-562
      keV in 3D mode, with the clinical scans giving the highest quality images with
      the same settings. CONCLUSION: Acquisition in 3D mode with a 425- to 650-keV or
      460- to 562-keV window leads to the highest image quality and contrast when
      imaging 124I in the presence of large amounts of 131I using a standard clinical
      PET scanner.

PMID- 16883020
TI  - In vitro studies on the signal transduction of thyroidal uptake of 18F-FDG and
      131I-Iodide.
AB  - Glucose metabolism in radioiodine-negative metastases of differentiated thyroid
      carcinomas (DTC) may still be increased by thyroid-stimulating hormone (TSH) as
      demonstrated by PET with 18F-FDG. The mechanisms of signal transduction involved
      in that process are as yet not completely understood. Therefore, the aim of this
      study was to investigate the effects of TSH, of an analog of cyclic adenosine
      monophosphate (dibutyryl cyclic AMP (Bu)2cAMP), and of inhibitors of the
      phosphatidylinositol 3-kinase (PI3-kinase) and of the protein kinase A (PKA) on
      18F-FDG and radioiodide uptake in the thyroid cell line FRTL-5. METHODS: FRTL-5
      cells were cultured in the presence of hormones with or without 1 mU/ mL TSH.
      Glucose carrier (GLUT-1) was determined by Western blot analysis. Cells were
      incubated with 0.5-1.0 MBq/mL 18F-FDG for 1 h or 18-37 kBq/mL 131I for 45 min,
      respectively, and tracer uptake was related to protein concentration. (Bu)2cAMP
      (1 mmol/L) was used as cAMP enhancer, H89 (0.25-25 micromol/L) as selective PKA
      inhibitor, and wortmannin (1 micromol/L) as inhibitor of PI3-kinase. RESULTS: TSH
      induced a 2.6-fold +/- 0.5 increase of radioiodide uptake in FRTL-5 cells (P <
      0.001, n = 8). The use of wortmannin inhibited TSH-induced uptake of 131I only
      moderately by 21.1% +/- 3.5% (P < 0.05, n = 8), whereas H89 markedly blocked the
      effect of TSH by 53.8% +/- 16.7% (P < 0.001, n = 8). TSH enhanced GLUT-1
      concentration of FRTL-5 cell membrane preparations by a factor of 1.6 (n = 3).
      TSH-treated cells showed a 2.6-fold increased uptake of 18F-FDG (P < 0.001, n =
      20). Stimulation by (Bu)2cAMP analogously increased 18F-FDG uptake (P < 0.001, n
      = 20). Wortmannin, but not H89, significantly inhibited TSH- and (Bu)2cAMP
      stimulation of 18F-FDG uptake by 42% +/- 25% (P < 0.001, n = 20) and 42% +/- 31%
      (P < 0.001, n = 20), respectively. CONCLUSION: The effect of TSH and cAMP on 18F
      FDG uptake by FRTL-5 cells is mediated by PI3-kinase and not by PKA, thus
      differing from the mechanism of radioiodide accumulation of this cell line. This
      observation is one possible explanation for the persistence of TSH-dependent 18F
      FDG uptake in radioiodine-negative metastases of DTC.

PMID- 16883021
TI  - An expert system for the detection of renal obstruction.

PMID- 16883024
TI  - Rheolytic thrombectomy in patients with ST-elevation myocardial infarction and
      large thrombus burden: the Thoraxcenter experience.
AB  - OBJECTIVES: To determine the impact of Rheolytic thrombectomy (RT) on the
      clinical and angiographic outcome of patients with ST-elevation myocardial
      infarction (STEMI) and large thrombus burden (LTB). METHODS: Two hundred sixty
      six consecutive patients who presented from April 2002 until December 2004 with
      STEMI and LTB were retrospectively analyzed. LTB was defined as definite presence
      of thrombus with the greatest dimension greater > or = 2 vessel diameters by
      visual assessment. RT, as well as the interventional procedure and the peri
      procedural pharmacological therapy, was at the discretion of the operator. All
      patients were followed for major adverse cardiac events (MACE) defined as death,
      non-fatal myocardial infarction (MI) and infarct-related artery
      revascularization. Pre- and post-procedural thrombolysis in myocardial infarction
      (TIMI) flow and thrombus burden as well as myocardial blush, distal embolization
      and no reflow were also determined. RESULTS: Complete follow-up was available in
      all patients; mean duration was 17 +/- 8.7 months. RT was used in 75 patients
      (28.2%). Stents were implanted in 251 (94.4%) patients; drug-eluting stents in
      210 (84.6%) patients (15.5% sirolimus-eluting stents and 69.1% paclitaxel-eluting
      stents). The 2-year cumulative survival and MACE-free survival were higher in the
      RT compared to the non-RT group (92% vs. 82.7%, p = 0.051 and 87.7% vs. 69.9%, p
      = 0.004, respectively). Post-procedure indices (TIMI 3 flow, absence of thrombus
      and myocardial blush grade 3) of angiographic outcome were significantly better
      in the RT group. RT was an independent predictor of MACE (HR: 0.45, 95% CI: 0.22
      0.93, p = 0.03). CONCLUSIONS: RT significantly improves the clinical and
      angiographic outcome of patients with STEMI and large thrombus burden.

PMID- 16883025
TI  - Improved outcome with AngioJet thrombectomy during primary stenting in acute
      myocardial infarction patients with high-grade thrombus.
AB  - BACKGROUND: Primary stenting during acute myocardial infarction (MI) is often
      complicated by slow-flow/no-reflow due to distal embolization of intracoronary
      thrombus. The AngioJet thrombectomy catheter has been utilized in this setting in
      order to limit distal embolization and improve flow. The effect of AngioJet
      during primary stenting in acute MI with high-grade thrombus (greater than or
      equal to grade 3, as per thrombolysis in MI [TIMI] classification) is not known.
      METHODS: We analyzed 95 consecutive acute MI patients with thrombus grade > or =
      3 who underwent primary stenting with AngioJet (n = 52) and without AngioJet (n =
      43) for epicardial and microvascular flow, and followed for 30-day major adverse
      cardiac events (MACE) and 1-year survival. Baseline characteristics and in
      hospital events were obtained from the interventional database. Two independent
      operators analyzed pre- and post-procedure TIMI flow rates, corrected TIMI frame
      count (CTFC) and TIMI myocardial perfusion grade (TMPG). RESULTS: Baseline
      clinical and angiographic characteristics were comparable between the two groups.
      AngioJet use was associated with better TIMI flow, TMP grade, CTFC and a trend
      towards lower 30-day and 1-year MACE. Use of AngioJet thrombectomy prior to
      stenting of acute MI patients with high-grade thrombus improves epicardial and
      microvascular flow, with a trend toward better short- and long-term outcome.

PMID- 16883026
TI  - AngioJet Rheolytic thrombectomy during rescue PCI for failed thrombolysis: a
      single-center experience.
AB  - BACKGROUND: Previous studies have shown the efficacy of AngioJet Rheolytic
      Thrombectomy (RT) in reducing thrombus burden and improving coronary flow in
      acute myocardial infarction (MI). No study has specifically evaluated the use of
      AngioJet RT in patients undergoing rescue percutaneous coronary intervention
      (PCI) for failed thrombolysis, a setting that may be particularly beneficial
      given the extensive thrombus burden. The objective of this study was to evaluate
      the efficacy and safety of AngioJet RT during rescue PCI for failed thrombolysis.
      METHODS: 214 consecutive patients were transferred to Good Samaritan Hospital to
      undergo rescue PCI for failed thrombolysis from January 2000 to October 2004.
      From this cohort, 32 patients (age 57 +/- 9, 30% male) undergoing AngioJet RT for
      rescue PCI (RT group) were identified and matched by initial thrombolysis in MI
      (TIMI) flow and infarct related artery (IRA) location to 32 patients (age 60 +/-
      12, 24% male) undergoing rescue PCI without AngioJet RT (Control group). TIMI
      frame count and TIMI thrombus grade were assessed at initial and final
      angiography. Angiographic success (TIMI 3 flow, < 50% residual stenosis) and in
      hospital clinical events, including bleeding complications and major adverse
      cardiac events (MACE) such as death, recurrent MI, target vessel
      revascularization and emergent bypass surgery were evaluated. Clinical success
      was defined as angiographic success in the absence of MACE. RESULTS: Baseline
      clinical characteristics were similar in both groups, except patients undergoing
      AngioJet RT were more likely to be males and less likely to be intubated on
      transfer. 30/32 (94%) patients achieved a TIMI thrombus grade of 0 in the RT
      group, compared to 22/32 (69%) in the Control group. Final IRA TIMI frame count
      was similar in the RT compared to the Control group (33 +/- 21 vs. 38 +/- 23, p
      NS, respectively). The occurrence of no reflow was significantly lower in the RT
      compared to the Control group (13% vs. 56%, p < 0.001, respectively). There was a
      trend for higher angiographic success in the RT compared to the control group
      (93% vs. 78%, p = 0.07, respectively). Clinical success was higher in the RT
      compared to the Control group (91% vs. 71%, p = 0.05, respectively). There were
      no differences in bleeding complications or MACE between the groups. CONCLUSION:
      AngioJet RT in high-risk patients undergoing rescue PCI for failed thrombolysis
      is safe and more effective in decreasing thrombus burden and preventing no reflow
      than conventional PCI.

PMID- 16883027
TI  - Safety of AngioJet thrombectomy in acute ST-segment elevation myocardial
      infarction: a large, single-center experience.
AB  - OBJECTIVES: To determine the clinical outcomes associated with use of AngioJet
      thrombectomy (AT) during percutaneous coronary intervention (PCI) for acute ST
      segment elevation myocardial infarction (STEMI). BACKGROUND: Embolization of
      thrombus and atherosclerotic plaque is thought to contribute to sub-optimal
      myocardial reperfusion and worse clinical outcomes in STEMI. However, in a recent
      randomized trial, a higher mortality and infarct size was observed in patients
      treated with AT. METHODS: We performed a retrospective analysis of all patients
      who underwent primary or rescue PCI for STEMI between January 2000 and December
      2005. Angiographic, procedural and in-hospital outcomes were compared between
      patients treated with or without AT. RESULTS: 1,260 STEMI patients underwent
      primary or rescue PCI at our hospital during the study period. Of these, 239
      (19%) underwent adjunctive treatment with AT. Patients treated with AT were more
      likely to be female, smokers and have a right coronary artery culprit. A slightly
      lower incidence of thrombolysis in myocardial infarction (TIMI) 3 grade flow was
      observed in the AT group after PCI (86% vs. 90%, p = 0.04). There was no
      significant difference in the incidence of in-lab ventricular
      tachycardia/ventricular fibrillation, vascular complications or transfusion
      between the study groups. The peak creatine kinase was higher in patients treated
      with AT. The incidence of in-hospital major adverse cardiac events was 7.5% in
      the AT group and 9.0% in the control group (p = NS). CONCLUSIONS: In this large,
      single-center experience, use of AT during mechanical reperfusion for STEMI was
      not associated with an increased risk of adverse outcomes. Our data suggest that
      AT may be performed safely in selected patients with STEMI.

PMID- 16883028
TI  - AngioJet experience from the multi-center STENT Registry.
AB  - OBJECTIVE: To explore the utilization and clinical outcomes of AngioJet Rheolytic
      thrombectomy from the Strategic Transcatheter Evaluation of New Therapies (STENT)
      multi-center prospective registry from May 2003 through December 2005. METHODS:
      Prospective consent was sought for all consecutive percutaneous coronary
      intervention (PCI) patients at all institutions and achieved in 84% of all
      patients. Of these, clinical follow-up at 9 months was achieved in 94% of
      eligible patients at all institutions. RESULTS: Of a total of 9,707 patients,
      AngioJet was utilized in 3-4% of all procedures, including 12-14% of all
      procedures with thrombolysis in myocardial infarction (TIMI) grade 3 thrombus or
      greater and 10-12% of acute evolving MI patients. Nine-month clinical outcomes
      showed similar mortality rates for patients treated with AngioJet (5.0%) versus
      those with no thrombectomy (6.5%) for patients with thrombus grade 3 or greater,
      despite the higher clinical risk profile of the AngioJet patient population due
      to a higher percentage of cardiogenic shock and larger thrombus. CONCLUSION: The
      results of this larger, multi-center registry indicate that AngioJet
      thrombectomy, when selected in general clinical practice for high risk patients
      with thrombus, results in non-significant numerically lower rate of mortality
      with no indication of safety issues.

PMID- 16883029
TI  - Adjunctive thrombectomy with primary percutaneous coronary intervention for ST
      elevation myocardial infarction: summary of randomized trials.
AB  - Primary percutaneous coronary intervention (PCI) for ST-segment elevation
      myocardial infarction (STEMI) achieves brisk coronary flow in > 90% of patients,
      but myocardial reperfusion (reperfusion at the tissue level) is often suboptimal,
      as evidenced by persistent ST-segment elevation and abnormal myocardial blush.
      Patients with suboptimal myocardial reperfusion have limited myocardial salvage
      and increased mortality. Distal micro-embolization may contribute to poor
      myocardial reperfusion, and this has stimulated great interest in the use of
      adjunctive thrombectomy with primary PCI in an attempt to prevent distal micro
      embolization and improve outcomes. In this paper, we review the randomized trials
      that have evaluated the use of adjunctive thrombectomy with primary PCI using
      three types of devices (X-sizer, aspiration thrombectomy and rheolytic
      thrombectomy). The results of these trials have been conflicting and the totality
      of evidence does not support the routine use of thrombectomy for removal of
      thrombus in patients with STEMI treated with primary PCI. In patients with large
      thrombus burden, distal macroembolization is common and is associated with poor
      outcomes. Adjunctive thrombectomy can effectively remove thrombus, and it seems
      appropriate to perform adjunctive thrombectomy prior to primary PCI in patients
      with large thrombus burden.

PMID- 16883030
TI  - Approaches to mechanical coronary thrombectomy.
AB  - Coronary thrombi are an integral part of acute coronary syndromes. Since the
      introduction of the AngioJet Rheolytic thrombectomy device in 1999, mechanical
      thrombectomy has replaced intracoronary thrombolysis during catheter-based
      procedures. Other approaches include simple suction aspiration, cut and aspirate
      devices and clot disruption by ultrasound or laser-induced cavitation. These
      device classes differ in the completeness of thrombus removal, ease of use,
      complication profile, as well as clinical evidence of benefit. The current
      approaches to mechanical thrombectomy are reviewed from these perspectives.

PMID- 16883031
TI  - Rheolytic thrombectomy in acute myocardial infarction: the Florence experience
      and objectives of the multicenter randomized JETSTENT trial.
AB  - The Florence-AngioJet randomized trial was the first study that assessed the
      efficacy of Rheolytic thrombectomy before direct infarct artery stent
      implantation in patients who underwent percutaneous coronary intervention (PCI)
      for acute myocardial infarction (MI). This study was based on a sample of 100
      patients with a first acute MI and the endpoints of the study were early ST
      segment resolution, corrected thrombolysis in myocardial infarction (TIMI) frame
      count, and infarct size as assessed by technetium-99m sestamibi scintigraphy at 1
      month. All 3 endpoints were reached. Patients randomized to thrombectomy before
      direct stenting had a higher incidence of early ST-segment elevation resolution
      (90% vs. 72%, p = 0.022), lower corrected TIMI frame counts (18.2 +/- 7.7 vs.
      22.5 +/- 11.0, p = 0.032), and smaller infarcts (13.0 +/- 11.6% vs. 21.2 +/-
      18.0%, p = 0.010) as compared to patients randomized to direct stenting alone.
      The AngioJET Thrombectomy and STENTing for Treatment of Acute Myocardial
      Infarction (JETSTENT) trial is a multi-center international randomized trial
      based on a sample of 500 patients with acute MI, the aim of which is the
      confirmation of the results of the Florence trial. Patients with a history of
      previous MI will be enrolled. No restriction based on clinical status on
      presentation or high-risk coronary anatomy will be used. Thus, patients with
      cardiogenic shock will be included. To be eligible, patients must have visible
      thrombus or a persisting total occlusion, and all use of AngioJet must follow the
      specific technique used in the Florence experience. The primary hypothesis of the
      study is that rheolytic thrombectomy before infarct artery stenting provides a
      better reperfusion as revealed by electrocardiogram and scintigraphy. The
      subsequent increase in myocardial salvage could result in a decreased incidence
      of death and heart congestive failure due to left ventricle remodeling at a mid
      term follow up.

PMID- 16883034
TI  - [Calcium homeostasis and diabetes mellitus].
AB  - Diabetes mellitus is associated with various organ dysfunctions through
      hyperglycemia, insulin deficiency, or advanced glycation end products, which can
      also cause impaired calcium homeostasis such as the reductions of parathyroid
      hormone secretion, vitamin D receptor (VDR) number, and 25- (OH) vitamin D-1
      alpha-hydroxylase activity in the parathyroid gland, intestine, and kidney,
      respectively. On the contrary, abnormal calcium homeostasis such as vitamin D
      deficiency/insensitivity and hyperparathyroidism can cause glucose intolerance or
      diabetes. Vitamin D deficiency/insensitivity induces type 2 diabetes through
      impaired insulin secretion involving VDR on pancreatic beta cells, as well as
      type 1 diabetes through the reduction in immuno-modulatory action of 1,25 (OH)(2)
      vitamin D. Primary hyperparathyroidism induces glucose intolerance via insulin
      resistance due to elevated intracellular calcium in the targeted organ of
      insulin.

PMID- 16883035
TI  - [Bone metabolic abnormality in diabetes: especially about osteoblast
      dysfunction].
AB  - As for the factor in the diabetes in which it takes part in a bone abnormal
      metabolism, this is given the insulin lack state, a high blood glucose state, and
      the complications accompanying diabetes, such as arteriosclerosis, neuropathy,
      and a renal dysfunction. The absolute, and/or relative insulin lack state
      deteriorate the function and reduce the number of osteoblast, in addition, the
      osteoblast dysfunction is also caused by the sorbitol accumulation brought in the
      osteoblast as the result of the continuation of high blood glucose state. It also
      prompts the osteoclastic bone absorption, and suppresses the expression of
      transcription factor gene that regulates the osteoblast differentiation, and
      resultantly, the apoptosis of the osteoblast is promoted. By these mechanisms
      intertwining, the differentiation and the maturity of the osteoblast is thought
      to be decrease and the bone formation process is obstructed.

PMID- 16883036
TI  - [Poor bone quality in diabetes: detrimental collagen cross-link pattern reduces
      bone strength without change in bone mineral density].
AB  - Although type 2 diabetes is often characterized by normal or high bone mineral
      density (BMD), diabetes is associated with increased risk of fracture. This
      paradoxical phenomenon in type 2 diabetes may be explained by poorer "bone
      quality" by detrimental collagen cross-links in bone. Recently, we showed that
      the alteration of enzymatic and nonenzymatic crosslinking in bone could be
      important for explaining the variation of fracture susceptibility in diabetes
      (Osteoporos Int, 2006. Epub ahead of print). In this review, we describe that low
      turnover bone, hyperglycemia, mildly hyperhomocysteinemia, and vitamin B(6)
      insufficiency are crucial determinants of detrimental crosslinking of bone
      collagen in diabetes.

PMID- 16883037
TI  - [Therapeutic approaches for diabetic osteopahty].
AB  - Although the clinical manifestations of diabetic osteopahty are not fully
      elucidated, diabetes may affect bone remodeling by various mechanisms, including
      deficiency of insulin actions, increased accumulation of advanced glycation end
      products and microangiopahty. The combination of subsequent poor bone quality of
      micro- or nano-architecture and frequent injurious falls would be related to an
      increase of fracture incidence. Several recent reports have revealed that older
      women with diabetes had a particularly increased risk of fractures. Bone mineral
      density (BMD) is the best predictor for fractures of primary osteoporosis, and
      increased risk for fractures of the type 1 diabetes is associated with the
      decrease of BMD, but not on the type 2 diabetes. The patients frequently show an
      increase of BMD, but suffer from fractures. At present, there is mostly no data
      what kind of intervention or pharmaceutical therapy is the best to avoid the
      incidence. Some in vivo studies support that vitamin K(2) (menatetrenone) may
      ameliorate bone quality damage in diabetics.

PMID- 16883038
TI  - [Increased fracture rate in patients with type 2 diabetes mellitus is independent
      of its bone mineral density].
AB  - Several large-scale clinical studies have recently revealed that both type 1 and
      type 2 diabetic patients are at higher risk for some fractures than those without
      diabetes. The fracture rate of type 1 diabetic patients has been reported to
      increase due to decreased bone mineral density. Type 2 diabetic patients also
      suffer from increased fracture rate, but bone mineral density is almost the same
      as those without diabetes, or even increase. Thus, the etiologies of fractures
      seem to be different between type 1 and type 2 diabetic patients. Increased
      fracture rate in type 2 diabetic patients may be partly explained by poor bone
      quality as well as the extra-skeletal factors like falling. Further studies are
      needed to clarify bone quality and the etiology of fractures in type 2 diabetes.

PMID- 16883039
TI  - [Diabetic vascular calcification and abnormal bone metabolism: the relation
      between bone and vascular].
AB  - High-frequency severe atherosclerosis/calcinosis is observed in diabetes mellitus
      and chronic dialysis, which leads to cardiovascular events. However, the
      effective treatment for suppressing the progression of vascular calcification has
      not been established. Here we review the mechanism of vascular calcification and
      present our findings that a first generation of bisphosphonate is useful in
      prevention of vascular calcification in diabetes and chronic renal failure.

PMID- 16883040
TI  - [The role of AGEs for the pathogenesis of osteopenia in diabetes mellitus].
AB  - Osteopenia was reported in patients with type I diabetes mellitus (DM). Also,
      serum levels of advanced glycation endproducts (AGEs) were reported to be
      elevated in DM. In this review, we showed the effect of AGEs on primary human
      osteoblasts, the precursor of human osteoclast like cells and parathyroid cells
      in culture. AGEs were made from incubating bovine serum albumin with glucose 6
      phosphate for 8 weeks (AGEs-BSA). AGEs-BSA (1,000 microg/mL) showed inhibitory
      effect for human osteoblasts in terms of the productions of procolagen c
      propeptide and osteocalcin, which were regarded as bone forming parameters. On
      the other hand, the same concentration of AGEs-BSA inhibited the increase in the
      parathyroid hormone secretion from the cultured human parathyroid cells induced
      by low calcium medium concentration. AGEs-BSA increased time dependently
      intracellular calcium levels of HEK 293 cells, which expressed the wild type
      human calcium-sensing receptor. Also, AGEs-BSA increased IL-6 synthesis by
      primary human osteoblast. Our preliminary data also showed that AGEs-BSA
      increased osteoclast-like cells formation in number from the osteoclast precursor
      rich bone marrow cells. These data suggested the important role of AGEs for the
      pathogenesis of osteopenia in patients with DM through decreased bone formation
      and increased bone resorption.

PMID- 16883041
TI  - [Negative correlation between BMD and HbA1C in patients with type 2 diabetes].
AB  - This study included 145 patients with type 2 diabetes, and 95 non-diabetic
      control. We measured bone mineral density (BMD) at the sites with different
      cortical/cancellous bone ratio (lumbar spine, femoral neck, and distal radius).
      BMD and Z score at the distal radius were significantly lower in type 2 diabetic
      patients than those in control subjects. In type 2 diabetic patients, negative
      correlation between BMD and the mean HbA(1C) during the last 2 years was found
      significantly at the distal radius in both sexes. These results indicate the
      selective cortical bone loss in type 2 diabetes, and suggest the importance of
      evaluating BMD at the radius as well and keeping good metabolic control to
      prevent bone loss in type 2 diabetic patients.

PMID- 16883042
TI  - [The effects of visceral fat accumulation by diabetes mellitus on bone
      metabolism].
AB  - The number of obesity and diabetes mellitus in the world has been rapidly
      increasing in population. Current lifestyle initiates obesity, especially
      visceral fat accumulation, and leads to the onset of metabolic syndrome, such as
      cardiovascular events, hyperlipidemia and diabetes mellitus, based on insulin
      resistance. Several studies of adipocyte function have revealed that adipose
      tissue is not merely an energy-storing organ but it secretes a variety of
      biologically active molecules, conceptualized as "adipocytokines", including
      tumor necrosis factor-alpha, estrogen, leptin and adiponectin and that abnormal
      secretion of these adipocytokines causes metabolic syndrome. Adipocytes exist not
      only in the visceral and subcutaneous tissue but also in the bone marrow.
      Therefore, it is important to know their effects not only on glucose and lipid
      metabolism but also on bone metabolism. This report aims to review some of the
      effects of visceral fat accumulation by diabetes mellitus on bone metabolism.

PMID- 16883043
TI  - [Bone abnormalities in diabetic hemodialysis patients].
AB  - In patients with end stage renal disease, metabolic bone abnormalities are
      frequently seen. Diabetes may affect bone metabolism through various mechanisms,
      including hyperglycemia, insulin deficiency, and accumulation of advanced
      glycation end-products. Bone disease in hemodialysis patients with diabetes
      mellitus is characterized by low bone turnover, resulting from either impaired
      secretion of parathyroid hormone or osteoblast dysfunction. The prevalence rate
      of vertebral fractures in diabetic hemodialysis patients was 32%, which was
      greater than that of non-diabetic hemodialysis patients (13%). In non-diabetic
      hemodialysis patients, those with vertebral fracture showed significantly lower
      bone mineral density in either lumbar spine or distal one third of radius than
      the respective value in those without fracture. However, in diabetic hemodialysis
      patients, neither bone mineral density in lumbar spine nor distal one third of
      radius was significantly lower in those with vertebral fracture than in those
      without.

PMID- 16883044
TI  - [Diabetic osteopahty and vitamin K].
AB  - Diabetes mellitus is considered as a risk factor for fractures, and there are
      some reports showing that metabolic effects of poor glycemic control resulted in
      lower bone turnover. Previous studies have revealed that this reduction of bone
      turnover increases bone fragility, independently of bone mineral density, so that
      the mechanisms of diabetic osteopahty seem to be more closely related to bone
      quality than bone quantity. The mechanisms of the preventive effect on fractures
      by vitamin K treatment should be related to amelioration of bone quality via
      increasing amounts of carboxylated osteocalcin. Therefore, administration of
      vitamin K(2) (menatetrenone) to the patients with diabetic osteopathy will be
      beneficial in order to improve the impaired bone quality and to reduce fracture
      risk.

PMID- 16883045
TI  - [Effect of aldose reductase on the abnormality of calcium metabolism in diabetic
      patients].
AB  - Bone disease in patients with type 2 diabetes mellitus (DM) is characterized by
      low bone turnover, resulting from either impaired secretion of parathyroid
      hormone or osteoblasts dysfunction. We have reported that intracellular sorbitol
      accumulation via. sorbitol pathway might be involved in the development of
      osteoblast dysfunction and osteoclast formation, as evidenced by either in vitro
      or in vivo study. The importance of metabolic pathway is further supported by the
      protective effect of aldose reductase inhibitor against the development of
      galactose-induced bone diseases in vivo and of functional impairments of human
      osteoblasts-like MG-63 cells. In conclusion, sorbotol pathway might be important
      in the development of low bone turnover disease in DM patients, and thus aldose
      reductase inhibitor might be clinically useful in the protection against the
      development of bone diseases in DM patients.

PMID- 16883046
TI  - [Diabetes mellitus and exercise].
AB  - Diabetes mellitus is one of the most important life-style related diseases. As
      for the type 2 diabetes mellitus in particular, lack of exercise has a large
      influence on the onset and disease progress. We can improve glucose tolerance by
      exercising. Exercise is the most important fundamental treatment in diabetes
      mellitus. Continuation and safety become important to let exercise therapy
      succeed. It is important with a diabetic that a lot of patients without exercise
      habit should start to gain exercise habit. When we expect an exercise effect, we
      should take consideration of intensity and volume in exercise for performing. We
      should consider each contraindication matter even if we put it to have many
      complications with a diabetic when we perform exercise therapy. A case-by-case
      exercise treatment in diabetic patient is required.

PMID- 16883047
TI  - [Notch signaling in chondrogenesis].
AB  - Notch is a signaling molecule which plays a critical role in the determination of
      multiple cellular differentiation pathways and morphogenesis in various
      biological systems, such as neurogenesis, immune system, and hematopoiesis.
      However, roles of Notch signaling in osteo/chondrogenesis have not been well
      studied. We will present our recent progress in investigating roles of Notch
      signaling in chondrogenesis using in vitro chondrogenic system. We will also
      discuss about the recent reports which used conditional knockout mice to
      investigate roles of Notch signaling molecules in vivo .

PMID- 16883048
TI  - [Mechanisms of synovial joint formation].
AB  - Synovial joints are comprised of relatively simple biomechanical structures
      including articular cartilage, synovial membrane, synovial fluid, ligaments and a
      fibrous capsule; they are fundamentally important for function and quality of
      life. Recent studies described the spatio-temporal expression patterns of
      signaling molecules and transcription factors in the developing synovial joints.
      Though few in number, the gain and/or loss of function-experiments demonstrated
      direct involvement of these molecules in joint formation. This review focuses on
      recent advances in understanding the mechanisms of synovial joint formation in
      the limbs.

PMID- 16883050
TI  - The mutational consequences of plant transformation.
AB  - Plant transformation is a genetic engineering tool for introducing transgenes
      into plant genomes. It is now being used for the breeding of commercial crops. A
      central feature of transformation is insertion of the transgene into plant
      chromosomal DNA. Transgene insertion is infrequently, if ever, a precise event.
      Mutations found at transgene insertion sites include deletions and rearrangements
      of host chromosomal DNA and introduction of superfluous DNA. Insertion sites
      introduced using Agrobacterium tumefaciens tend to have simpler structures but
      can be associated with extensive chromosomal rearrangements, while those of
      particle bombardment appear invariably to be associated with deletion and
      extensive scrambling of inserted and chromosomal DNA. Ancillary procedures
      associated with plant transformation, including tissue culture and infection with
      A tumefaciens, can also introduce mutations. These genome-wide mutations can
      number from hundreds to many thousands per diploid genome. Despite the fact that
      confidence in the safety and dependability of crop species rests significantly on
      their genetic integrity, the frequency of transformation-induced mutations and
      their importance as potential biosafety hazards are poorly understood.

PMID- 16883049
TI  - Histone deacetylase enzymes as potential drug targets in cancer and parasitic
      diseases.
AB  - The elucidation of the mechanisms of transcriptional activation and repression in
      eukaryotic cells has shed light on the important role of acetylation
      deacetylation of histones mediated by histone acetyltransferases (HATs) and
      histone deacetylases (HDACs), respectively. Another group belonging to the large
      family of sirtuins (silent information regulators (SIRs)) has an (nicotinamide
      adenine dinucleotide) NAD(+)-dependent HDAC activity. Several inhibitors of HDACs
      (HDIs) have been shown to exert antitumor effects. Interestingly, some of the
      HDIs exerted a broad spectrum of antiprotozoal activity. The purpose of this
      review is to analyze some of the current data related to the deacetylase enzymes
      as a possible target for drug development in cancer and parasitic diseases with
      special reference to protozoan infections. Given the structural differences among
      members of this family of enzymes, development of specific inhibitors will not
      only allow selective therapeutic intervention, but may also provide a powerful
      tool for functional study of these enzymes.

PMID- 16883051
TI  - Evidence of a genomic biomarker in normal human epithelial mammary cell line, MCF
      10A, that is absent in the human breast cancer cell line, MCF-7.
AB  - This study investigated the use of DNA amplification fingerprinting (DAF) to
      identify biomarkers useful in the elucidating genetic factors that lead to
      carcinogenesis. The DNA amplification fingerprinting (DAF) technique was used to
      generate fingerprint profiles of a normal human mammary epithelial cell line (MCF
      10A) and a human breast cancer cell line (MCF-7). When compared with one another,
      a polymorphic biomarker gene (262 base pairs (bps)) was identified in MCF-10A but
      was not present in MCF-7. This gene was cloned from the genomic DNA of the MCF
      10A cell line, and subjected to Genbank database analysis. The analysis of the
      nucleotide sequence polymorphic marker (Genbank account: AC079630) shows that
      this biomarker has 100% homology with the nucleotide sequence of human chromosome
      12 BAC RP11-476D10 (bps 19612-19353). The nucleotide sequence was used for
      possible protein translation product and the result obtained indicated that the
      gene codes for hypothetical protein XF2620. In order to evaluate the effects that
      the 262 bps biomarker would have on the morphology of MCF-7 cells, it was
      transfected into MCF-7 cells. There were observable changes in the morphology of
      the transfected cells. These changes included an increase in cell elongation and
      a decrease in cell aggregation.

PMID- 16883052
TI  - Reduced atherosclerotic lesion size in P-selectin deficient apolipoprotein E
      knockout mice fed a chow but not a fat diet.
AB  - P-selectin. We investigated the role of P-selectin on the development of vascular
      lesions in an ApoE(-/-) male mice. Double-knockout (ApoE(-/-), P-selectin(-/-);
      DKO) were compared to single-knockout (ApoE(-/-); SKO) mice. They were fed a chow
      or fat diet for 3, 6, 15, and 20 weeks, without any differences in cholesterol
      levels. DKO mice fed a chow diet exhibited a ratio of lesion area over media
      lower than SKO mice, for 3 (P < .03) , 6 (P < .001), and 15 (P < .02) weeks. DKO
      mice fed a fat diet showed a lower ratio only at 3 weeks. P-selectin deficiency
      in ApoE(-/-) mice has a protective effect in atherosclerotic lesions development.
      Reduction of lesion size depends on diet type and duration. A fat diet could
      neutralize the beneficial effects of P-selectin deficiency, inducing
      atherosclerotic lesions via probably other adhesion molecules.

PMID- 16883053
TI  - Biosynthesis of antitumoral and bactericidal sanguinarine.
AB  - A simple, rapid, and reliable TLC method for the separation and determination of
      sanguinarine has been established. This intensively studied biologically active
      alkaloid has a wide range of potentially useful medicinal properties, such as
      antimicrobial, antiinflammatory, and antitumoral activities. Sanguinarine has
      also been incorporated into expectorant mixtures and has a strong bactericidal
      effect upon gram-positive bacteria, particularly Bacillus anthracis and
      staphylococci. These medicinal properties are due to the interaction of
      sanguinarine with DNA. A fibre-optic-based fluorescence instrument for in situ
      scanning was used for quantitative measurements. The sanguinarine was determined
      over the range 5-40 ng and a detection limit of 1.60 ng. The method was applied
      to the quantification of sanguinarine in tissue culture extracts of Chelidonium
      majus L.

PMID- 16883054
TI  - Cloning and expression of human membrane-bound and soluble engineered T cell
      receptors for immunotherapy.
AB  - We report here the design and construction of several gene vectors for expression
      in mammalian cells of membrane-bound and soluble human T cell receptors (TR). We
      designed a vector (TR-ALPHA-IRES-TR-BETA pEF4) that encodes high-level expression
      of the full-length TR on the surface of T cells. Furthermore, we engineered TR
      that does not require the presence of endogenous CD3 molecules for surface
      expression and thus expression is not limited to T cells. We also constructed a
      vector encoding a single-chain TR (scTR) as a fusion protein of V-ALPHA-V-BETA-C
      BETA with CD3Z. Since it is encoded and expressed as a single molecule, this scTR
      is well suited for gene therapy. Lastly, we successfully used a mammalian
      expression vector for generation of soluble human TR. The approaches we used here
      for manipulation of a human tumor-specific TR can be useful for other
      investigators interested in TR-based immunotherapy.

PMID- 16883055
TI  - Site-directed mutagenesis to assess the binding capacity of class s protein of
      Staphylococcus aureus leucotoxins to the surface of polymorphonuclear cells.
AB  - Staphylococcal leucotoxins result from the association of class S components and
      class F component inducing the activation and the permeabilization of the target
      cells. Like alpha-toxin, the leucotoxins are pore-forming toxins with more than
      70% beta-sheet. This was confirmed by attenuated total reflectance Fourier
      transform infrared (ATR-FTIR) spectroscopy. In addition, threonine 28 of a
      predicted and conserved beta-sheet at the N-terminal extremity of class S
      proteins composing leucotoxins aligns with histidine 35 of alpha-toxin, which has
      a key role in oligomerization of the final pore. Flow cytometry was used to study
      different aminoacid substitutions of the threonine 28 in order to evaluate its
      role in the biological activity of these class S proteins. Finally, results show
      that threonine 28 of the leucotoxin probably plays a role similar to that of
      histidine 35 of alpha-toxin. Mutations on this threonin largely influenced the
      secondary interaction of the class F component and led to inactive toxin.

PMID- 16883056
TI  - Apocynin derivatives interrupt intracellular signaling resulting in decreased
      migration in breast cancer cells.
AB  - Cancer cells are defined by their ability to divide uncontrollably and
      metastasize to secondary sites in the body. Consequently, tumor cell migration
      represents a promising target for anticancer drug development. Using our high
      throughput cell migration assay, we have screened several classes of compounds
      for noncytotoxic tumor cell migration inhibiting activity. One such compound,
      apocynin (4-acetovanillone), is oxidized by peroxidases to yield a variety of
      oligophenolic and quinone-type compounds that are recognized inhibitors of NADPH
      oxidase and may be inhibitors of the small G protein Rac1 that controls cell
      migration. We report here that while apocynin itself is not effective, apocynin
      derivatives inhibit migration of the breast cancer cell line MDA-MB-435 at
      subtoxic concentrations; the migration of nonmalignant MCF10A breast cells is
      unaffected. These compounds also cause a significant rearrangement of the actin
      cytoskeleton, cell rounding, and decreased levels of active Rac1 and its related
      G protein Cdc42. These results may suggest a promising new route to the
      development of novel anticancer therapeutics.

PMID- 16883057
TI  - Fuzzy logic in medicine and bioinformatics.
AB  - The purpose of this paper is to present a general view of the current
      applications of fuzzy logic in medicine and bioinformatics. We particularly
      review the medical literature using fuzzy logic. We then recall the geometrical
      interpretation of fuzzy sets as points in a fuzzy hypercube and present two
      concrete illustrations in medicine (drug addictions) and in bioinformatics
      (comparison of genomes).

PMID- 16883058
TI  - Neutrophil secretion induced by an intracellular Ca2+ rise and followed by whole
      cell patch-clamp recordings occurs without any selective mobilization of
      different granule populations.
AB  - We have investigated calcium-induced secretion in human neutrophils, using a
      whole-cell patch-clamp technique. Mobilization of subcellular granules to the
      cell membrane was followed as the change in membrane capacitance (deltaC(m)).
      Both the magnitude and the kinetics of the response differed between low and high
      concentrations of Ca(2+). A sustained secretion following a short lag phase was
      induced by high concentrations of Ca(2+) (100 microM and higher). A stable
      plateau was reached after 5-7 minutes at deltaC(m) values corresponding to values
      expected after all specific as well as azurophil granules have been mobilized.
      Capacitance values of the same magnitude could be obtained also at lower Ca(2+)
      concentrations, but typically no stable plateau was reached within the measuring
      time. In contrast to previous studies, we were unable to detect any pattern of
      secretion corresponding to a distinct submaximal response or selective
      mobilization of granule subsets specified by their Ca(2+)-sensitivity.

PMID- 16883059
TI  - Determination of DNA damage in floriculturists exposed to mixtures of pesticides.
AB  - The aim of the study was to determine possible DNA damage in floriculturists
      chronically exposed to pesticides. Leukocytes from 52 workers, 46 environmentally
      exposed, and 38 control individuals were evaluated with the comet assay. Serum
      from all individuals was also analyzed for pesticides using gas chromatography
      coupled to mass spectrometry. A statistically significant difference in DNA
      fragmentation in the pesticide exposed group compared to the other two groups (P
      < .001) was found. No differences between environmentally exposed and control
      individuals were detected. The statistical analysis showed no significant
      correlation between DNA damage and sex, age, drinking or smoking habits, as well
      as years of exposure. One or more pesticides were detected in 50% of the
      floriculturists, while in the rest of the individuals, a chemical related with
      the preparation of pesticides, such as additives, plasticizers, or solvents, was
      found. Our study shows that chronic exposure to pesticides produces DNA damage in
      floriculturists. It also suggests that this type of monitoring could be valuable
      in recommending preventive measures.

PMID- 16883060
TI  - Tubulointerstitial macrophage accumulation is regulated by sequentially expressed
      osteopontin and macrophage colony-stimulating factor: implication for the role of
      atorvastatin.
AB  - Infiltration and local proliferation are known factors that contribute to
      tubulointerstitial macrophage accumulation. This study explored the time course
      of these two contributors' roles as tubulointerstitial inflammation and fibrosis
      progressing, and evaluated the mechanisms of the protective effect of
      atorvastatin. Unilateral ureteral obstructive (UUO) rats were treated with
      atorvastatin (10 mg/Kg) or vehicle. Expression of osteopontin (OPN) and
      macrophage colony-stimulating factor (M-CSF) was evaluated by RT-PCR and
      immunohistochemistry. Immunohistochemistry staining of ED1 was used to assess
      macrophage accumulation in interstitium. Histological evaluation was performed to
      semiquantify tubulointerstitial fibrosis. The results showed that on day 3 after
      UUO operation, OPN expression significantly increased and positively correlated
      with the number of the interstitial ED1(+) cells, while on day 10, M-CSF
      expression upregulated and correlated with interstitial ED1(+) cells. In
      atorvastatin treatment group, the increments of these two factors were attenuated
      significantly at the two time points, respectively. ED1(+) cell accumulation and
      fibrosis also ameliorated in the treatment group. For all the samples of UUO and
      treatment group on day 10, ED1(+) cells also correlated with interstitial
      fibrosis scores. The results suggest that OPN may induce the early
      macrophage/monocyte infiltration and M-CSF may play an important role in
      regulating macrophage accumulation in later stage of UUO nephropathy. Statin
      treatment decreases interstitial inflammation and fibrosis, and this
      renoprotective effect may be mediated by downregulating the expression of OPN and
      M-CSF.

PMID- 16883061
TI  - JAK inhibitors AG-490 and WHI-P154 decrease IFN-gamma-induced iNOS expression and
      NO production in macrophages.
AB  - In inflammation, inducible nitric oxide synthase (iNOS) produces nitric oxide
      (NO), which modulates inflammatory processes. We investigated the effects of
      Janus kinase (JAK) inhibitors, AG-490 and WHI-P154, on iNOS expression and NO
      production in J774 murine macrophages stimulated with interferon-gamma (IFN
      gamma). JAK inhibitors AG-490 and WHI-P154 decreased IFN-gamma-induced nuclear
      levels of signal transducer and activator of transcription 1alpha (STAT1alpha).
      JAK inhibitors AG-490 and WHI-P154 decreased also iNOS protein and mRNA
      expression and NO production in a concentration-dependent manner. Neither of the
      JAK inhibitors affected the decay of iNOS mRNA when determined by actinomycin D
      assay. Our results suggest that the inhibition of JAK-STAT1-pathway by AG-490 or
      WHI-P154 leads to the attenuation of iNOS expression and NO production in IFN
      gamma-stimulated macrophages.

PMID- 16883062
TI  - Serum IL-18 is increased at early postburn period in moderately burned patients.
AB  - A severe systemic inflammatory response is usually seen after burn injury. IL-18
      enhances the Th1 immune responses in bacterial andviral infections. In order to
      evaluate the IL-18 serum levels as well as IL-6 and TNF-alpha at the 48th hour
      postburn, serial serum samples of 8 burned patients were analyzed. 8 moderately
      burned patients were included into the study. Serum samples were taken at
      admission at the 48th hour of postburn. IL-6, IL-18, and TNF-alpha serum levels
      were analyzed. Total mean burned surface area (TBSA) was 24.6 +/- 5.7% and mean
      BMI (body mass index) was 24.5 +/- 3.4. The patients' age ranged from 17 to 38
      (mean 26.3 +/- 7.4) years. An increase in sera IL-6, IL-18, and TNF-alpha was
      detected at the 48th hour postburn (P < .0001). All patients survived. A marked
      increase in serum levels of IL-18 as well as the other cytokines evaluated was
      observed in the moderately burned patients. These three parameters were highly
      correlated with each other (r > 0.9 and P < .001). This is the first study that
      shows an increase in serum IL-18 levels at the early postburn period.

PMID- 16883063
TI  - Myeloperoxidase promoter polymorphism -463G is associated with more severe
      clinical expression of cystic fibrosis pulmonary disease.
AB  - The severity of cystic fibrosis (CF) pulmonary disease is not directly related to
      CFTR genotype but depends upon several parameters, including neutrophil-dominated
      inflammation. Identification of agents modulating inflammation constitutes a
      relevant goal. Myeloperoxidase (MPO) is involved in both microbicidal and
      proinflammatory neutrophil activities. The aim of this study was to evaluate
      whether the -463GA MPO promoter polymorphism is linked to clinical severity of CF
      associated pulmonary inflammation. This polymorphism significantly affects the
      level of MPO gene expression in leukocytes and the G allele is more expressing
      than the A allele. We show that MPO genotype significantly influences the
      severity of pulmonary disease in early stages, prior to the development of
      chronic lung infections, with GG genotype being associated with more severe CF
      disease. Our findings indicate that the level of MPO gene expression influences
      the CF pathogenesis, presumably reflecting cellular damage by MPO-generated
      oxidants or other activity of MPO in airway inflammation.

PMID- 16883064
TI  - Serum leptin is not a diagnostic marker for familial Mediterranean fever attacks.
AB  - The aim of our study is to determine whether there is a relationship between
      familial Mediterranean fever (FMF) attacks and serum leptin levels. We enrolled
      25 patients (22 males and 3 females) and 25 healthy controls (21 males and 4
      females) with a mean age of 24.42 +/- 1.22 (Mean +/- SEM) years and 24.30 +/-
      1.19 years (Mean +/- SEM), respectively. We investigated serum levels of leptin,
      interleukin-6 (IL-6) erythrocyte sedimentation rate (ESR), C-reactive protein
      (CRP),fibrinogen, and leukocyte counts before the attack and 8-12 hours after the
      attack started. The same parameters have been investigated in the control
      subjects. The mean serum leptin levels before the attacks were 6.45 +/- 1.05
      (Mean +/- SEM) and during the attacks were 7.59 +/- 1.3 (Mean +/- SEM) in FMF
      group,respectively. There was a slight increase in serum leptin levels during the
      attacks but it was not statistically significant (P > .05). The mean serum leptin
      levels were 16.12 +/- 2.81 in the control group which were not different from the
      mean serum leptin levels before and during the attack periods in the study group
      (P > .05). However, there were statistical differences in the serum levels of IL
      6, ESR, CRP, fibrinogen, and leukocyte counts before and during the attack
      periods (P > .05). No correlation was found between serum leptin levels and IL-6,
      ESR, CRP, fibrinogen, and leukocyte counts (P > .05). Serum leptin levels do not
      increase during FMF attacks and therefore it is not useful for diagnostic
      purposes and follow-up during treatment.

PMID- 16883065
TI  - NKT cells in the induced sputum of severe asthmatics.
AB  - To determine whether there was a specific inflammatory process in severe
      asthmatics, the phenotypic characteristics of induced sputum immune cells were
      analysed among patients with severe asthma. Twenty-two induced sputa (10 severe
      asthmatics) were studied. Flow cytometric analysis was performed using immune
      cells of the sputum and monoclonal antibodies to CD3, CD4, CD8, CD56, CD25, and
      TCRgammadelta. The number of NKT (CD3(+) CD56(+)) cells was significantly higher
      in the sputum of severe asthmatics compared with mild asthmatic and healthy
      control groups (P < .05). CD8(+)CD56(+) cells were the predominant subtype of the
      increased NKT cells in severe asthmatics. CD3(+)CD56(+)Valpha24(+),
      TCRgammadelta(+) CD56(+), and CD4(+)CD25(+) T cells were significantly increased
      in severe asthmatic patients. These results suggest that the immunopathogenesis
      of severe asthmatics vary between severe and mild asthmatics, and that
      CD8(+)CD56(+) NKT cells may play an important role in the immunopathogenesis of
      severe asthma.

PMID- 16883067
TI  - A subgroup of first-degree relatives of Crohn's disease patients shows a profile
      of inflammatory markers in the blood which is more typical of Crohn's disease
      patients than of normal individuals.
AB  - INTRODUCTION: Family member with IBD is the greatest risk factor for developing
      the disease. The hematological profileof first-degree relatives (FDRs) of Crohn's
      disease (CD) patients was studied in order to identify healthy FDRs at risk to
      develop disease. MATERIALS AND METHODS: Thirty CD patients, 90 FDRs, and 28 non
      related individuals (controls) were enrolled. Hematological profile and C
      reactive protein were determined. RESULTS: All hematological parameters were
      significantly different in CD patients compared to controls, with significantly
      higher levels of CRP, WBC, PMN, MONO, and PLT and lower Hb and lymphocyte count.
      The hematological profile of FDRs showed values between the controls and CD
      patients with ten FDRs that their parameters matched those of CD patients and
      significantly different from other FDRs. This group was defined as high-risk
      relatives (HRRs). CONCLUSIONS: Analysis of the hematological profile and CRP
      level might be proven as a fast, reliable, and less money-consuming tool to
      identify FDRs with a probable increased risk to develop the disease.

PMID- 16883066
TI  - Regulation of annexin I in rheumatoid synovial cells by glucocorticoids and
      interleukin-1.
AB  - The glucocorticoid (GC)-induced antiinflammatory molecule annexin I is expressed
      in leukocytes and has antiinflammatory effects in animal models of arthritis, but
      the expression of annexin I in rheumatoid arthritis (RA) fibroblast-like
      synoviocytes (FLS) is unknown. We report the constitutive and dexamethasone (DEX)
      inducible expression of annexin I in RA FLS. DEX increased FLS annexin I protein
      translocation and mRNA expression. Interleukin (IL)-1beta also induced annexin I
      translocation and mRNA but also increased intracellular protein. DEX and IL-1 had
      additive effects on annexin I mRNA, but DEX inhibited the inducing effect of IL
      1beta on cell surface annexin I. These results indicate that glucocorticoids and
      IL-1beta upregulate the synthesis and translocation of annexin I in RA FLS, but
      interdependent signalling pathways are involved.

PMID- 16883068
TI  - Interleukin-1 modulation of human placental trophoblast proliferation.
AB  - During early pregnancy, interleukin-1 (IL-1) is mainly produced and secreted by
      maternal decidua. Yet, its biological function on placental cells is not well
      defined. In this study, we employed JAR choriocarcinoma cell line as a model of
      human placental trophoblast to study the effect of IL-1. Treatment with
      recombinant human IL-1beta resulted in significant inhibition of JAR
      proliferation (P < .05) paralleled with increased cytotoxicity. The inhibitory
      effect was blocked by both IL-1 receptor antagonist (IL-1Ra) and antihuman IL
      1beta monoclonal antibody. Analyzing the mode of action, IL-1beta was found to
      induce cell cycle arrest in the G0/G1 phase and triggered apoptotic cell death.
      These findings demonstrated that IL-1 regulates human trophoblast growth by
      induction of cell cycle delay and cell death.

PMID- 16883069
TI  - Lymphocyte subpopulations in pulmonary tuberculosis patients.
AB  - Protection against Mycobacterium tuberculosis is based on cell-mediated immunity,
      most importantly involving CD4(+) and CD8(+) T-cell subsets. The aim of this
      study was to evaluate CD4(+) and CD8(+) T-cell profiles and CD19(+) and
      CD3(+)CD(16 + 56)(+) populations in patients with pulmonary tuberculosis. CD4(+)
      and CD8(+) T cells, B-lymphocytes, and natural killer (NK) cells were evaluated
      in 75 active (APTB) and 25 inactive (IPTB) pulmonary tuberculosis cases and 20
      healthy subjects (HCs). The results were compared at different stages of
      antituberculosis treatment in the APTB patients and also according to X-ray
      findings in the newly diagnosed APTB patients. The percentages of CD4(+) T cells
      were significantly lower (P < .01) and those of CD3(+)CD(16+56)(+) cells were
      significantly higher (P < .01) in APTB patients than in HCs. CD8(+) T cells were
      significantly decreased (P < .05), and CD3(-)CD(16+56)(+) cells were
      significantly increased (P < .01), in IPTB patients compared to HCs. The
      percentages of CD4(+), CD8(+), CD3(-)CD19(+), and CD3(-)CD(16+56)(+) cells showed
      no differences at different times of the antituberculosis regimen, and different
      stages of newly diagnosed APTB patients. APTB patients have a reduced percentage
      of circulating CD4(+) T cells and an increased percentage of NK cells compared
      with healthy individuals. These cells could play important roles in the immune
      response to M tuberculosis infection.

PMID- 16883071
TI  - Chronic hepatitis C and Crohn's disease: nosocomial infection treatment with PEG
      interferon plus ribavirin.
AB  - We describe the case of a patient with a diagnosis of Crohn's disease and
      accidental infection during abdominal surgery by hepatitis C virus (HCV) who
      received combination therapy with pegylated interferon-alpha2b (1.5 microg/kg
      weekly) plus ribavirin (10.6 mg/kg daily) for histologically demonstrated chronic
      hepatitis C. After 48 weeks treatment, serum transaminase levels were normal and
      viremia (HCV RNA) was negative (end-of-treatment response); 24 weeks later
      (follow-up period), a sustained virological response was demonstrated. The
      tolerance to combination antiviral therapy was good, without intestinal symptoms
      of inflammatory bowel disease recurrence. We conclude that current antiviral
      therapies with immunomodulatory effects may be helpful and safe for patients with
      inflammatory bowel disease infected by hepatitis C virus.

PMID- 16883072
TI  - Proton pump inhibitor failure: why does it occur and how can it be managed?

PMID- 16883070
TI  - Glutamate receptors in neuroinflammatory demyelinating disease.
AB  - Multiple sclerosis (MS) is a chronic demyelinating disease of the human central
      nervous system (CNS). The condition predominantly affects young adults and is
      characterised by immunological and inflammatory changes in the periphery and CNS
      that contribute to neurovascular disruption, haemopoietic cell invasion of target
      tissues, and demyelination of nerve fibres which culminate in neurological
      deficits that relapse and remit or are progressive. The main features of MS can
      be reproduced in the inducible animal counterpart, experimental autoimmune
      encephalomyelitis (EAE). The search for new MS treatments invariably employs EAE
      to determine drug activity and provide a rationale for exploring clinical
      efficacy. The preclinical development of compounds for MS has generally followed
      a conventional, immunotherapeutic route. However, over the past decade, a group
      of compounds that suppress EAE but have no apparent immunomodulatory activity
      have emerged. These drugs interact with the N-methyl-D-aspartate (NMDA) and alpha
      amino-3-hydroxy-5-isoxazolepropionic acid (AMPA)/kainate family of glutamate
      receptors reported to control neurovascular permeability, inflammatory mediator
      synthesis, and resident glial cell functions including CNS myelination. The
      review considers the importance of the glutamate receptors in EAE and MS
      pathogenesis. The use of receptor antagonists to control EAE is also discussed
      together with the possibility of therapeutic application in demyelinating
      disease.

PMID- 16883074
TI  - [Effective or not? The decision is yours! - the PEK HTA reports].

PMID- 16883073
TI  - Refractory heartburn to proton pump inhibitors: epidemiology, etiology and
      management.
AB  - Patients with refractory heartburn to proton pump inhibitors (PPIs) represent a
      distinctive group which is difficult to manage. In a systematic review of the
      relative literature we found that approximately 20% of patients with erosive
      esophagitis and 15-25% of patients with normal endoscopy and abnormal 24-hour
      esophageal pH monitoring continue to report heartburn despite treatment with
      standard dose PPIs. Furthermore, approximately 30-40% of patients with normal
      endoscopy and 24-hour pH studies and 15-20% of patients with Barrett's esophagus
      have refractory heartburn to double dose PPIs. In such cases, compliance to
      therapy, duodeno-gastroesophageal reflux, gastro-esophageal motility disorders
      and eradication of Helicobacter pylori infection may contribute to symptoms.
      Based on the available evidence, we suggested an algorithm for the evaluation and
      management of these patients.

PMID- 16883075
TI  - Use of complementary medicine in Switzerland.
AB  - OBJECTIVE: Within the framework of the Swiss governmental Program of Evaluation
      of Complementary Medicine (PEK) we assessed the prevalence, use, perceived
      effectiveness and appreciation of complementary medicine (CAM) in Switzerland,
      according to published surveys. MATERIALS AND METHODS: Search was performed
      through electronic databases, by hand-searching and by contacting experts at
      universities, hospitals, health insurances, patient organizations and
      pharmaceutical companies. RESULTS: Surveys were carried out among the general
      population (40%), physicians (20%), hospitalized patients (30%) and obstetric
      institutions (5%). The number of publications increased strongly between 1981 and
      2004. The mean +/- SD prevalence (use) of CAM is 49 +/- 22% and varies depending
      on the survey's topic and the population group interviewed. The acceptance,
      appreciation or demand for CAM among individuals specifically interviewed on CAM
      is 91 +/- 6%. When asked about favored general improvements in healthcare, 6.5%
      of the individuals spontaneously mentioned CAM. CAM therapies are considered to
      be effective by the majority of CAM users and by about 40% of cancer patients
      using CAM. Approximately 50% of the population stated a preference for hospitals
      that also provide CAM. 85% of the population wishes the costs for CAM to be
      covered by the basic health insurance. CONCLUSION: Approximately half of the
      Swiss population has used CAM. CAM treatment is considered to be effective by the
      majority of CAM users. About 50% of the population would prefer hospitals that
      also provide CAM therapies and the majority of the population wishes the cost for
      CAM therapies to be covered by basic health insurance.

PMID- 16883076
TI  - [Anthroposophic medicine: health technology assessment report - short version].
AB  - BACKGROUND AND OBJECTIVE: The aim of this Health Technology Assessment Report was
      to analyse the current situation, efficacy, effectiveness, safety, utilization,
      and costs of Anthroposophic Medicine (AM) with special emphasis on everyday
      practice. DESIGN: Systematic review. MATERIAL AND METHODS: Search of 20
      databases, reference lists and expert consultations. Criteriabased analysis was
      performed to assess methodological quality and external validity of the studies.
      RESULTS: AM is a complementary medical system that extends conventional medicine
      and provides specific pharmacological and non-pharmacological treatments. It
      covers all areas of medicine. 178 clinical trials on efficacy and effectiveness
      were identified: 17 RCTs, 21 prospective and 43 retrospective NRCTs, 50
      prospective and 47 retrospective cohort studies/case-series without control
      groups. They investigated a wide range of AM-treatments in a variety of diseases,
      90 x mistletoe in cancer. 170 trials had a positive result for AM. Methodological
      quality differed substantially; some studies showed major limitations, others
      were reasonably well conducted. Trials of better quality still showed a positive
      result. External validity was usually high. Side effects or other risks are rare.
      AM-patients are well educated, often female, aged 30-50 years, or children. The
      few economic investigations found less or equal costs in AM because of reduced
      hospital admissions and less prescriptions of medications. CONCLUSION: Trials of
      varying design and quality in a variety of diseases predominantly describe good
      clinical outcome for AM, little side effects, high satisfaction of patients and
      presumably slightly less costs. More research and more methodological expertise
      and infrastructure are desirable.

PMID- 16883077
TI  - Effectiveness, safety and cost-effectiveness of homeopathy in general practice -
      summarized health technology assessment.
AB  - INTRODUCTION: The Health Technology Assessment report on effectiveness, cost
      effectiveness and appropriateness of homeopathy was compiled on behalf of the
      Swiss Federal Office for Public Health (BAG) within the framework of the 'Program
      of Evaluation of Complementary Medicine (PEK)'. MATERIALS AND METHODS: Databases
      accessible by Internet were systematically searched, complemented by manual
      search and contacts with experts, and evaluated according to internal and
      external validity criteria. RESULTS: Many high-quality investigations of pre
      clinical basic research proved homeopathic high-potencies inducing regulative and
      specific changes in cells or living organisms. 20 of 22 systematic reviews
      detected at least a trend in favor of homeopathy. In our estimation 5 studies
      yielded results indicating clear evidence for homeopathic therapy. The evaluation
      of 29 studies in the domain 'Upper Respiratory Tract Infections/Allergic
      Reactions' showed a positive overall result in favor of homeopathy. 6 out of 7
      controlled studies were at least equivalent to conventional medical
      interventions. 8 out of 16 placebo-controlled studies were significant in favor
      of homeopathy. Swiss regulations grant a high degree of safety due to product and
      training requirements for homeopathic physicians. Applied properly, classical
      homeopathy has few side-effects and the use of high-potencies is free of toxic
      effects. A general health-economic statement about homeopathy cannot be made from
      the available data. CONCLUSION: Taking internal and external validity criteria
      into account, effectiveness of homeopathy can be supported by clinical evidence
      and professional and adequate application be regarded as safe. Reliable
      statements of cost-effectiveness are not available at the moment. External and
      model validity will have to be taken more strongly into consideration in future
      studies.

PMID- 16883078
TI  - Traditional Chinese medicine (phytotherapy): Health Technology Assessment report 
      selected aspects.
AB  - OBJECTIVE: A summary of main aspects from a Health Technology Assessment report
      on Traditional Chinese Medicine (TCM) in Switzerland concerning effectiveness and
      safety is given. MATERIALS AND METHODS: Literature search was performed through
      13 databases, by scanning reference lists of articles and by contacting experts.
      Assessed were quality of documentation, internal and external validity. RESULTS:
      Effectiveness: 43 articles concerning 'gastrointestinal tract and liver' were
      assessed. The studies covering 7,436 patients were undertaken in China (35),
      Japan (3), USA (2) and Australia (3); 33/43 being controlled studies. 34/40 show
      significantly better results in the TCM-treated group. A comparison of studies on
      results of treatment based on a diagnosis according to TCM criteria and studies
      on results of treatment according to Western diagnosis shows that treatment based
      on TCM diagnosis improves the result. The comparison of treatment by individual
      medication and standard medication showed a trend in favor of individual
      medication. SAFETY: TCM training and practice for physicians in Switzerland are
      officially regulated. Side effects occur, but no severe effects have been
      registered up to now in Switzerland. TCM medicinals are imported; admission
      regulations are being installed. Problems due to production abroad, Internet
      trade, self-medication or admixtures are possible. CONCLUSION: The evaluation of
      the literature search provides evidence for a basic clinical effectiveness of TCM
      therapy. Severe side effects were not observed in Switzerland. Regulations for
      trading and use of medicinals prevent treatment risks. Further clinical studies
      in a Western context are required.

PMID- 16883079
TI  - Complementary and alternative medicine costs - a systematic literature review.
AB  - OBJECTIVE: The aim of this literature review, performed within the framework of
      the Swiss governmental Program of Evaluation of Complementary Medicine (PEK), was
      to investigate costs of complementary and alternative medicine (CAM). MATERIALS
      AND METHODS: A systematic literature search was conducted in 11 electronic
      databases. All retrieved titles and reference lists were also hand-searched.
      RESULTS: 38 publications were found: 23 on CAM of various definitions (medical
      and non-medical practitioners, over-the-counter products), 13 on homeopathy, 2 on
      phytotherapy. Studies investigated different kinds of costs (direct or indirect)
      and used different methods (prospective or retrospective questionnaires, data
      analyses, cost-effectiveness models). Most studies report 'out of pocket' costs,
      because CAM is usually not covered by health insurance. Costs per CAM-treatment /
      patient / month were AUD 7-66, CAD 250 and GBP 13.62 +/- 1.61. Costs per
      treatment were EUR 205 (range: 15-1,278), USD 414 +/- 269 and USD 1,127. In two
      analyses phytotherapy proved to be cost-effective. One study revealed a reduction
      of 1.5 days of absenteeism from work in the CAM group compared to conventionally
      treated patients. Another study, performed by a health insurance company reported
      a slight increase in direct costs for CAM. Costs for CAM covered by insurance
      companies amounted to approximately 0.2-0.5% of the total healthcare budget
      (Switzerland, 2003). Publications had several limitations, e.g. efficacy of
      therapies was rarely reported. As compared to conventional patients, CAM patients
      tend to cause lower costs. CONCLUSION: Results suggest lower costs for CAM than
      for conventional patients, but the limited methodological quality lowers the
      significance of the available data. Further well-designed studies and models are
      required.

PMID- 16883080
TI  - Emerging global epidemic of obesity: the renal perspective.
AB  - Obesity, as a core component of the metabolic syndrome, is among the top ten
      global health risks classified by the World Health Organization (WHO) as being
      strongly associated with the development and progression of chronic renal disease
      -a widely prevalent but often silent condition. Obesity carries elevated risks of
      cardiovascular morbidity and mortality besides having an array of metabolic
      complications. Maladaptive glomerular hemodynamics with increased intraglomerular
      pressure in association with vasoactive, fibrogenic substances released from
      adipocytes, in addition to cytokines and hormones, are the key factors in the
      causation of renal injury and the progression of nephron loss among obese
      subjects.

PMID- 16883081
TI  - Spontaneous singleton and twin pregnancy in two patients with polycystic ovary
      syndrome and type 2 diabetes following treatment with metformin combined with
      rosiglitazone.
AB  - Two women, a Saudi Arab and a Caucasian, aged 28 and 41 years, had a long history
      of polycystic ovary syndrome (PCOS) and primary infertility, which was refractory
      to various treatment modalities. Both later developed type 2 diabetes, managed
      initially with metformin; rosiglitazone was added later to improve glycaemic
      control. Both conceived spontaneously, resulting in singleton and twin
      pregnancies giving birth to healthy babies. The combination of rosiglitazone with
      metformin may result in improved fertility with ovulation and spontaneous
      conception in women with PCOS and type 2 diabetes. Randomized controlled trials
      are needed to assess the feasibility of this combination to improve fertility in
      women with PCOS. However, in the absence of any safety data, those women,
      following counselling, should be warned against the possibility of spontaneous
      pregnancy and contraceptive measures should be discussed and offered where
      appropriate.

PMID- 16883082
TI  - Knowledge of breast cancer and its risk and protective factors among women in
      Riyadh.
AB  - BACKGROUND: We conducted this study to assess knowledge of breast cancer and
      sources of information about breast cancer among women in Riyadh. We also
      analyzed whether associations existed between demographic variables, knowledge of
      breast cancer, and the practice of breast self-examination and use of mammography
      screening. METHODS: Women interested in participating in this community-based
      descriptive study provided data by completing a pre-tested structured RESULTS: Of
      864 participating women, 84% were Saudi, 45% were married and 67.8% had a
      university level education. Eighty percent were between the ages of 20 to 50
      years. Knowledge of breast self examination (BSE) was high; 82% (95% confidence
      intervals [CI], 79.2%-84.4%) knew about BSE, while 61% (95% CI: 57.9%-64.5%) knew
      about mammography, but only 41.2% (95% CI, 37.9%-44.5%) had performed BSE and
      18.2% (95%CI, 15.5%-20.8%) had had mammography screening. Knowledge of breast
      cancer, risk factors and protective factors for breast cancer was moderate. There
      was a statistically significant association between the demographic
      characteristics (marital status, educational status and family history of breast
      cancer) and knowledge and practice of BSE and CONCLUSION: Though it has
      limitations, this study revealed an imbalance between the knowledge and practice
      of BSE among women. It also showed that there is only moderate knowledge of risk
      and protective factors for breast cancer and that knowledge and practice of BSE
      and mammograms vary according to marital and educational status. Hence, frequent
      community-based awareness programs are needed so that all women can know and
      practice BSE, which in turn helps to prevent breast cancer.

PMID- 16883083
TI  - Complications of bronchoscopy for foreign body removal: experience in 1,035
      cases.
AB  - BACKGROUND: Tracheobronchial foreign body aspirations, which threaten lives in
      childhood, also carry potential risks during and after bronchoscopy. The aim of
      this study is to review complications and precautions that need to be taken
      against possible risks. METHODS: From 1987 to 2005, bronchoscopy was done in
      1,035 children in our department on suspicion of foreign body aspiration. The
      average age of these patients, mostly male (55%), was 4.1 years. Medical history,
      physical examination, radiological methods and bronchoscopy were used in the
      diagnosis. Bronchoscopy was applied under general anaesthesia, and the
      respiratory and cardiac systems were closely observed for 4 hours after the
      process. RESULTS: Nine hundred eleven of 1,035 patients (88%) had a foreign body
      in the tracheobronchial system. In 42 of the patients, infection required
      aggressive medication; in 30, hypoxia and bradycardia occurred as a result of
      obstruction during bronchoscopy; in 37, laryngeal edema, laryngeal spasm and/or
      bronchospasm required ventilation support; in 6 patients, tracheobronchial system
      bleeding occurred; in 2 patients pneumothorax occurred, in 1 patient
      pneumomediastinum was observed and 6 patients needed thoracotomies because of
      foreign body aspiration. In this series there were 8 deaths. CONCLUSION:
      Bronchoscopy, performed for tracheobronchial foreign body aspiration, carries a
      potential life-threatening risk during and after the process. The clinician needs
      to be aware of these risks, take proper precautions, and perform bronchoscopy by
      taking the medical condition of the patient and characteristics of the inspired
      foreign body into consideration.

PMID- 16883084
TI  - Hypertension control and co-morbidities in primary health care centers in Riyadh.
AB  - BACKGROUND: The prevalence of hypertension in Saudi Arabia has been assessed only
      in preliminary reports. The aim of this study was to determine the degree of
      control of blood pressure and the prevalence of common hypertension co
      morbidities among hypertensive patients at-tending primary healthcare (PHC)
      centers in Riyadh. METHODS: A cross-sectional study was conducted by reviewing
      medi-cal records of hypertensive patients during May and June 2001. Two hundred
      fifty-five medical records were selected by a stratified randomization process
      according to the distribution of 73 PHC centers in the city and the total number
      of hypertensive patients registered in the mini-clinic of each PHC center.
      Trained mini-clinic nurses collected data using a data collection form developed
      for this purpose. RESULTS: Of 255 patients, 121 (47.5%) were males and 134
      (52.5%) were females; the mean age was 57.2+/-11.1 years and 8.3% were smokers.
      The majority, 204 (85.7%), had greater than normal body weight. Only 101 (40.4%)
      had controlled systolic BP and 129 (51.6%) had controlled diastolic BP. The most
      common co-morbidity was diabetes mellitus, found in 98 (38.4%), followed by
      dyslipidemia in 50 (19.6%), bronchial asthma in 28 (11.0%) and renal diseases in
      12 (4.7%). Except for osteoporosis, which was reported by females only (P=0.003),
      the occurrence of hypertensive co-morbidities did not vary from other demographic
      characteristics. CONCLUSION: This study demonstrated poor blood pressure control
      in the mini-clinics in PHC centers. To improve the quality of care for
      hypertensive patients, we recommend an improvement in PHC physician knowledge of
      and attitudes toward the importance of achieving targeted blood pressure levels.

PMID- 16883085
TI  - Safety of percutaneous renal biopsy as an outpatient procedure in pediatric
      patients.

PMID- 16883086
TI  - Cerebrospinal fluid nerve growth factor levels in patients with Alzheimer's
      disease.
AB  - BACKGROUND: Alzheimer's disease (AD) is the most common cause of dementia in
      Western countries and in Japan. Numerous blood and cerebrospinal fluid (CSF)
      tests based on the disease pathology have been proposed for early detection of
      AD. By comparing the CSF proteome of AD patients and controls it might be
      possible to identify proteins that play a role in the disease process and thus
      study the pathogenesis of AD. PATIENTS AND METHODS: Samples of CSF from normal
      (n=20) and AD patients (n=20) were collected by lumbar puncture. The total
      concentration of proteins in the CSF of normal subjects and AD patients was
      determined by Bio-Rad protein assay based on the Bradford dye binding procedure.
      The presence and level of NGF in the CSF of normal and AD patients was measured
      by enzyme-linked immunosorbent assay (ELISA), SDS-PAGE and western blot. RESULTS:
      The total protein concentration of all samples was within the normal range (0.10
      0.44 g/L). A western blot analysis using anti-NGF antibody showed the presence of
      NGF in human CSF. By ELISA, the level of NGF in the CSF of AD patients was higher
      than in the CSF of normal subjects (81.5A+/-15.03 pg/mL vs. 4.2A+/-1.92 pg/mL,
      P<0.0001). CONCLUSION: We suggest that the NGF level in the CSF may provide
      additional information in the differential diagnosis of AD. We also conclude that
      NGF could be significantly involved in the pathophysiology of AD.

PMID- 16883087
TI  - Surgical anatomy of the inguinal canal in children.

PMID- 16883088
TI  - [Management of bronchial asthma].

PMID- 16883089
TI  - [Molecular mechanisms of IgE synthesis].

PMID- 16883091
TI  - [Feature of food allergy developed during infancy (2)--acquisition of tolerance
      against hen's egg, cow's milk, wheat, and soybean up to 3 years old].
AB  - BACKGROUND: Once food elimination is introduced, it is important to know for
      doctors when patients generally develop oral tolerance against eliminated food.
      To clarify the point, following study was conducted. METHODS: We analyzed 304
      patient profiles with food allergy in our division between 1994 and 2001. The
      diagnosis of oral tolerance was determined by the results of food challenges or
      the accidental episodes of ingestion. RESULTS: By the age of 3 years old, 78% of
      food allergy patients with soybean, 63% of those with wheat, 60% of those with
      cow's milk, 51% of those with egg yolk, and 31% of those with egg white developed
      oral tolerance, respectively. IgE CAP RAST scores against cow's milk, egg yolk,
      and egg white in the patients without tolerance were significantly higher than
      those in the patients with tolerance. CONCLUSION: Patients developed oral
      tolerance firstly against soybean followed by wheat, cow's milk, egg yolk and egg
      white during the first 3 years of life. The specific IgE antibody levels against
      egg and cow's milk are important for the diagnosis of tolerance.

PMID- 16883090
TI  - [A genetic study of an allergic disease--the present conditions and future
      prospects].

PMID- 16883092
TI  - [Cost-effectiveness of fluticasone propionate for asthma episodes in Japanese
      patients with asthma--Fluticasone Investigation of Asthma Episode (FINE) study].
AB  - BACKGROUND: To discuss and estimate the economic benefits gained by fluticasone
      propionate (FP) for patients with asthma over hospitalization, emergency room
      visit, unscheduled visit, and absence (representative by asthma-related episode).
      METHOD: Asthma-related episodes in pre and post 6 months of FP use were derived
      from a survey of FP on asthma-related episodes (FINE study). Medical cost was
      evaluated by macro-cost estimate and productivity loss by human capital approach.
      RESULTS: Discussion of asthma-related episodes in-between before and after the
      use of FP in eight hundred ninety-eight valuable subjects revealed that FP use
      significantly reduced asthma-related episodic costs of approximately 120,000 yen
      (p<0.001), whereas total drug acquisition costs for being newly consumed FP,
      leukotriene receptor antagonists, inhaled short-acting beta2 agonists, etc were
      significantly increased by approximately 16,000 yen. Moreover, while
      significantly avoiding productivity loss of approximately about 35,000 yen it
      totally provided cost-savings of about 70,000 yen at the patients' viewpoint.
      When sensitivity analyses were performed by adjusting the confounding factors
      using analysis of covariance, the aforementioned base case results might be
      persistent. For safety of FP, some adverse events related to the use of FP were
      identified of about 2.0%, and there were not any serious ones at all. CONCLUSION:
      The economic evaluation of FP demonstrated that it is sufficient, whereas an
      acquisition cost was increased. Use of FP economically impacts on Japanese
      society and patients.

PMID- 16883093
TI  - [Comparison of clinical efficacy and cost-quality of antihistamines in early
      treatment for Japanese cedar pollinosis].
AB  - BACKGROUND: Japanese cedar pollinosis (JCP) affects more than 16% of the Japanese
      population. The estimated direct and indirect costs for this disease totaled 286
      billion yen in 1998. In JCP therapy, antihistamines are first line agents. It is
      well known that starting treatment for JCP with antihistamines before initial day
      of the pollen scattering can relieve nasal symptom severity during pollen season.
      The aim of this study is to assess the clinical efficacy and cost-quality of 7
      major second-generation antihistamines in early treatment for Japanese cedar
      pollinosis (JCP). METHODS: Patients were randomly selected from 16 ENT clinical
      sites in Osaka and Wakayama between February 24 and March 8, 2003 (peak pollen
      season). Effectiveness was assessed using patient'ratings of nasal and ocular
      symptoms and overall assessment in their condition compared to previous season
      ones. Costs include direct costs of the drugs used for treatment to JCP from
      January to March. RESULTS: One hundred seventy-five patients who were treated
      with antihistamine monotherapy (azelastine: n=15, cetirizine: n=15, ebastine:
      n=36, epinastine: n=16, fexofenadine: n=16, loratadine: n=60, oxatomide: n=17)
      and 510 non-treatment patients were evaluated. Among 8 groups, there were
      significant differences in sneezing, rhinorrhea, ocular itching and overall
      health condition. However, among 7 monotherapy groups, there were no differences
      in each symptom or the overall assessment. In cost-quality analysis, there were
      significant differences in a cost for each effective patient (defined as those
      with improvement in their overall condition) among 7 drugs. The top three cost
      efficacious drugs resulted in azelastine, loratadine and fexofenadine.
      CONCLUSION: These results show that there were no significant differences in
      clinical efficacy in early treatment for JCP among 7 antihistamines. But Japanese
      National Health Insurance drug price scheme led to significant differences in
      cost-quality.

PMID- 16883094
TI  - [A questionnaire survey of asthma in children with co-morbid allergic rhinitis].
AB  - BACKGROUND: Bronchial asthma is often complicated with allergic rhinitis (AR).
      OBJECTIVE: To investigate the relationship between the upper and lower airway
      diseases in children with asthma, we performed a questionnaire survey at 6
      centers in Kinki area in Japan. METHODS: A questionnaire was filled out by
      parents of 333 asthmatic children (0-16 years, median age 7). It included
      questions concerning nasal symptoms, onset ages of rhinitis and asthma,
      correlation between nasal symptoms and asthma symptoms, and family history of
      allergic diseases. RESULTS: One hundred and fifty five (46.5%) subjects answered
      to have any nasal diseases; 20 with sinusitis, 46 with seasonal AR, and 119
      (35.7%) with perennial AR. To further clarify the relationship of asthma and
      concomitant AR, we focused on patients with perennial AR and compared the
      clinical characteristics with patients with no nasal diseases. Percentage of non
      atopic asthma was significantly lower in patients with comorbid AR than those
      without. Severity of asthma tended to be milder and family history of perennial
      AR was more often in the former than the latter group. Interestingly, asthmatic
      children with comorbid AR were more likely to have cold air-induced asthma
      exacerbations. In the subjects with comorbid AR, concomitant exacerbation of the
      upper and lower airways occurred in 38.7%. The median age of onset of asthma and
      nasal symptoms was 2 and 4 years, respectively. In 43.9% of them, upper airway
      symptoms started either before or simultaneously with asthma. CONCLUSION: The
      attention should be paid to the nasal symptoms in children with asthma,
      especially they have atopic asthma and positive family history of perennial
      allergic rhinitis. It is important that an appropriate diagnosis and treatment of
      nasal symptoms to better control asthma in children.

PMID- 16883096
TI  - [Management of acute exacerbation in adult asthmatics: current strategy and
      perspective].

PMID- 16883095
TI  - [A case of anaphlaxis caused by mite-contaminated Okonomi-yaki].
AB  - A 21-year-old man, who had suddenly developed dyspnea with sneeze, cough and
      nasal congestion following supper, was admitted to our hospital because of
      hypoxemia and hypercapnia. Physical examination revealed wheezing in all lung
      fields and skin flushing. He took home-made Okonomi-yaki made from flour, which
      had been opened few months ago, and then had been remained uncooked at room
      temperature. Skin prick tests showed positive for problem flour and mite, but
      negative for just opened control flour. Collectively, we gave his diagnosis of
      anaphylaxis caused by mite-contaminated Okonomi-yaki.

PMID- 16883097
TI  - [Immunological aspects of the pathogenesis of asthma].

PMID- 16883098
TI  - [Diagnosis, treatment and management of hypersensitive reactions to food and food
      additives].

PMID- 16883099
TI  - [An epidemiologic study on prevalence of allergen-specific IgE antibodies in
      school children living in rural area of Saitama Prefecture, Japan].
AB  - BACKGROUND: In order to estimate the sensitization to inhalant allergen in
      childhood, prevalence of allergen-specific IgE antibodies was retrospectively
      surveyed on sera from school children aged from 9 to 15 living in rural area of
      Saitama prefecture, Japan, in 2001 and five years ago from 2001 (1996). METHODS:
      Allergen-specific IgE antibodies against Japanese cedar pollen (JCP), ragweed,
      sweet vernal grass, Dermatophagoides pteronyssinus (Dp), house dust (HD) and cat
      dander were examined on sera from 79 school children aged from 9 to 11 (group A)
      and 119 school children aged from 12 to 15 (group B) collected in 2001, and sera
      from 117 school children aged from 9 to 11 and 56 school children aged from 12 to
      15 collected in 1996. Furthermore, a questionnaire survey about diagnosis of any
      allergic diseases and symptoms associated with the diseases was conducted on the
      same subjects in 2001. RESULTS: On the survey from school children, group A and
      B, collected in 2001, percentage of positive cases for allergen-specific IgE
      antibodies against any of 6 allergens were 49 in both of the groups for JCP, 10
      and 12 for ragweed, 18 and 19 for sweet vernal grass, 39 in both of the groups
      for Dp, 42 in both of the groups for HD, 23 and 14 for cat dander, respectively.
      On the survey from school children collected in 1996, there is no significant
      difference from the percentage of positive cases for allergen-specific IgE
      antibodies against each allergen in 2001. Among the subjects followed-up on the
      survey in both of the years, the percentage of positive cases for allergen
      specific IgE antibodies against each of six allergens on the survey in 2001
      increased as compared with those in 1996. As a result of questionnaire survey in
      2001, percentage (70: group A, 89: group B) of positive cases for allergen
      specific IgE antibodies against any 6 allergens in the subjects with any symptoms
      associated with allergic diseases, but not diagnosed, was significantly higher
      than the percentage (34: group A, 48: group B) of that in the subjects without
      any symptoms associated with the diseases. CONCLUSION: Further prospective study
      is required to clarify a cause of allergic diseases in childhood, and it should
      be taken precautionary measures during childhood against sensitization with
      inhalant allergen to prevent allergic diseases in surveyed area.

PMID- 16883100
TI  - [Effects of proton pump inhibitor on airway hyperresponsiveness in asthmatics
      with gastroesophageal reflux].
AB  - BACKGROUND: Previous data suggest the high incidence of gastroesophageal reflux
      (GER) in asthmatics, although the relationship between GER and the respiratory
      condition in asthmatics remain unclear. We investigated the incidence of GER in
      asthmatics and the association between the effects of proton-pump inhibitor (PPI)
      on respiratory functions and esophageal pH in asthmatics with GER. METHODS: Two
      hundreds ninety outpatients who attended our unit with asthma received GER
      symptoms questionnaire used at Mayo Clinic. Twenty three of them who answered to
      have any GER symptom were treated with PPI (lansoprazole 30 mg/day) for eight
      weeks, and investigated changes in the GER symptoms and peak expiratory flow
      rates (PEFR) before and after treatment. Furthermore, in six of twenty three,
      airway hyperresponsiveness to methacholine and esophageal pH monitor for 24 hours
      were measured in order to evaluate the association between esophageal pH and the
      effect of PPI on GER during the test. Furthermore, the serum level of
      theophylline was analyzed for assessment of the PPI effect on theophylline
      metabolism. RESULTS: 150 of 290 asthmatics had answered to have any GER symptom
      including cough. Most of GER symptoms had improved except for cough after
      treatment with PPI. The airway hyperresponsiveness significantly improved after
      treatment with PPI (n=6, p<0.03), although PEF and FEV1 were not significantly
      changed. CONCLUSION: These results suggest that PPI may be an effective drug for
      asthmatics with GER through suppression of airway hyperresponsiveness.

PMID- 16883101
TI  - [Total serum IgE levels in eosinophilic lung diseases].
AB  - BACKGROUND: We previously reported elevated levels of total serum IgE in patients
      with asthma, regardless of their atopic status. We hypothesized that certain
      factors inherent to asthma may contribute to this non-specific elevation of total
      serum IgE. In the current study, to evaluate the role of eosinophils in the
      regulation of total serum IgE, we examined whether peripheral blood eosinophil
      count is associated with total serum IgE level in patients with eosinophilic lung
      diseases. METHODS: Ninety-nine healthy controls, 277 patients with asthma, 15
      patients with acute eosinophilic pneumonia, 21 patients with chronic eosinophilic
      pneumonia were studied for total serum IgE levels and peripheral blood eosinophil
      counts. RESULTS: Patients with acute or chronic eosinophilic pneumonia had
      significantly increased total serum IgE levels compared with healthy controls
      regardless as atopic status (p<0.001). In non-atopic subjects with eosinophilic
      lung diseases, total serum IgE level was significantly correlated with peripheral
      blood eosinophil count (r=0.42, p<0.001, n=57). CONCLUSION: Our findings suggest
      that, in addition to antigen-specific IgE production, non-specific IgE production
      may contribute to elevated levels of total serum IgE in patients with asthma or
      eosinophilic pneumonia. An increased number of activated eosinophils may underlie
      an increased total serum IgE level in these conditions.

PMID- 16883102
TI  - [A long-term follow-up study after discontinuation of immunotherapy for Japanese
      cedar pollinosis].
AB  - BACKGROUND: To elucidate how long the effect of immunotherapy (IT) persist after
      discontinuation in patients with Japanese cedar pollinosis (JCP). METHODS: After
      discontinuation of IT 485 patients with JCP who completed one course of IT for
      3.6 years in average were followed repeatedly up by means of author's original
      evaluation system of symptom-medication system from 1996 to 2005 using the method
      of questionnaire. Since the variations of terms after discontinuation and times
      of examination existed, the outcomes were averaged in every one year and follow
      up seasons after discontinuation. Comparison of score and type in the year of
      discontinuation (base-line level) with those of follow-up was made for evaluation
      of outcomes. In addition, of these, 100 JCP patients, who had both intervals of 3
      years or more from the discontinuation and examination times of 3 or more during
      the follow-up period, were examined as the evidence of reliability. RESULTS:
      Although the scores and types in each year were affected slightly by yearly
      changes in air borne pollen count, the effect persisted for 10 years with a
      slight change, keeping score 3 to 4. Forty two% of patients had no symptom and
      medication even in 2005, a year of large pollen count. Conclusively effect of the
      JCP IT persists satisfactorily for at least 10 years. This is the first study of
      long term follow-up in JCP against cross sectional study.

PMID- 16883103
TI  - [Hypersensitivity reactions to multiple drugs during the course of hairy cell
      leukemia treated with 2-chlorodeoxyadenosine].
AB  - A 38-year-man developed diffuse erythema 3 days after the administration of 2
      chlorodeoxyadenosine (cladribine or 2-CdA) and many other drugs for hairy cell
      leukemia (HCL). Patch-testing and scratch patch-testing showed positive reactions
      for clindamycin (10%, 30%) at 24 hours and 48 hours. Furthermore, provocation
      testing showed positive reactions for sulfamethoxazole.trimethoprim, allopurinol,
      fluconazole, so our diagnosis was erythroderma-type drug eruption due to
      clindamycin, sulfamethoxazole-trimethoprim, allopurinol, fluconazole. Cutaneous
      side-effects associated with cladribine have seldom been described in cases of
      HCL. Our case suggests that there is a relationship between the drug
      hypersensitivity and the prolonged suppressed CD4 cell levels caused by
      cladribine.

PMID- 16883104
TI  - [The pathomechanisms and treatment of atopic dermatitis].

PMID- 16883105
TI  - [New Japanese pediatric guideline for the treatment and management of asthma
      2005].

PMID- 16883106
TI  - [Diagnosis and treatment of allergic conjunctival disease].

PMID- 16883107
TI  - [Right and wrong of salmeterol/fluticasone propionate combination].
AB  - Although salmeterol (SLM)/fluticasone propionate (FP) combination has been widely
      used in the world, this is not yet available in Japan. The combination risk was
      concerned based on overseas reports about adrenal suppression with high dose FP
      or asthma exacerbation from undesirable administration of SLM without ICS.
      Therefore, in this article, it was reviewed the evidence of both efficacy profile
      and safety profile of the SLM/FP for the combination with FP and SLM, and it was
      concluded that safety concerns of SLM and FP are low and the benefits of SLM/FP
      combination exceed the risks, at least they are used properly. Since SLM/FP
      combination has synergic effect clinically, this will reduce high dose used FP
      and they also reduce using SLM without ICS. The compliance will be improved by
      the combination. To improve asthma control, Japanese clinicians expect to be
      available this combination soon.

PMID- 16883108
TI  - [Local differences of oral allergy syndrome with pollinosis--a comparison between
      Hanshinkan and Higashiharima in south Hyogo].
AB  - BACKGROUND: A number of cases of oral allergy syndrome (OAS) to fruits with birch
      pollinosis have been described. The antigen of Alnus sieboldiana (alder) trees
      which are massively planted on Rokko Mountain appeared to be highly similar to
      birch pollen. METHODS: We took the medical history of pollinosis and OAS,
      measured pollen-specific IgE (CAP-RAST) and performed prick tests of causative
      fruits to the outpatients of the two hospitals in different areas. RESULT: In
      Hanshinkan district, at the foot of Rokko Mountain, we experienced 9 cases of OAS
      among 377 outpatients. All 9 cases had alder specific-IgE. The prevalence rate of
      OAS was 11.0% in the alder specific-IgE-positive patients and 0% in the alder
      specific-IgE-negative patients in the area. On the other hand, in Higashiharima
      district where less alder trees exist and further from Rokko Mountain, 19 OAS
      patients were documented among 2000 outpatients. Six of the 19 patients with OAS
      did not have alder specific-IgE. The prevalence rate of OAS was 6.8% in the alder
      specific-IgE-positive patients and 11.8% in the mugwort specific-IgE-positive
      patients in the area. CONCLUSION: In Hanshinkan, alder pollinosis seems to be
      most important for the cross reactivity to the OAS. In Higashiharima, mugwort
      pollinosis may be more important than alder pollinosis for the cross reactivity
      to the OAS.

PMID- 16883109
TI  - [Cytoprotective effects of heat shock protein-70 in bronchial epithelium against
      neutrophil elastase-induced cell injury].
AB  - BACKGROUND: Neutrophil releases several mediators during inflammation, including
      neutrophil elastase (NE) that impairs bronchial epithelial function. The stress
      response and stress proteins protect cells against a variety of cytotoxic
      conditions. Accordingly, we tested the hypothesis that bronchial epithelial heat
      shock protein (Hsp-70) would protect a NE-induced cell injury. METHODS: Bronchial
      epithelial cells (BECs) obtained by bronchial brushing under bronchoscopy were
      cultured and used for experiments. Expression of Hsp-70 in BECs was confirmed by
      Western blot and flowcytometric analysis. To test Hsp-70 in BECs, induction of
      Hsp-70 protein into BECs was carried out by liposome-based delivery system.
      Introduction of Hsp-70 into BECs were examined by direct fluorescence microscope
      examination and flowcytometric analysis. NE-induced cytotoxicity was evaluated by
      cell culture supernatant LDH assay and cell detachment assay. RESULTS: Higher
      expressions of Hsp-70 were observed in BECs, which were induced by sodium
      arsenite. Over expression of Hsp-70 in BECs reduced NE-induced cell injury.
      Introduction of Hsp-70 protein into BECs by liposomal delivery decreased LDH
      release, and inhibited necrosis and apoptosis of the cells by NE as compared to
      untreated control. CONCLUSION: These data suggested that Hsp-70 in BECs may
      inhibit NE-induced airway epithelial damage. Liposomal delivery of Hsp-70 into
      BECs may be a possible means of protecting bronchial epithelium against
      inflammatory airway diseases including acute and chronic bronchitis.

PMID- 16883110
TI  - [A case of systemic sclerosis and Sjogren's syndrome with cardiac tamponade due
      to steroid-responsive pericarditis].
AB  - A 75-year-old woman was admitted to our hospital because of abnormal lung shadow
      and necrosis of the left feet. She had a history of Raynaud's phenomenon from her
      twenties. On admission, she was diagnosed as having diffuse systemic sclerosis
      (SSc) and Sjogren's syndrome (SjS) because of scleroderma, interstitial pneumonia
      (IP), positive result of anti-Scl-70 and SS-A antibody, sicca, decreased tear
      excretion, and dysfunction of salivary glands. Seventy days after amputation of
      her left leg, she presented with edema, hypoxemia, chest discomfort, and fever.
      Blood test revealed inflammation and cardiac echography revealed pericardial
      effusion with a collapse sign of right atrium, thereby leading to the diagnosis
      of cardiac tamponade. After starting the daily dose of 20 mg of prednisolone, the
      pericardial effusion and cardiac tamponade sign disappeared. Pericarditis is seen
      in half of patients with SSc and rarely with SjS, and is usually asymptomatic.
      Pericarditis due to SSc has been reported unresponsive to steroid therapy, but
      several cases of steroid responsive pericarditis due to SSc or SjS have been
      reported. Clinically, they shared inflammatory responses and the presence of IP
      in the cases of SSc, which will be important when considering the pathogenesis
      and treatment of pericarditis due to SSc or SjS.

PMID- 16883111
TI  - [A case of "late-onset" anaphylaxis caused by fermented soybeans; Natto].
AB  - Natto is a Japanese traditional food made from fermented soybeans. We report a
      case of anaphylaxis caused by natto and review the literature. The patient was a
      22-year-old man who showed systemic eruption with itching and pectoralgia about
      10 hours after eating a meal containing natto. Results of skin tests for soybean
      allergen were negative, and the allergen remained unidentified. We then used a
      food elimination trial to confirm the allergy. However the patient did not
      refrain from eating natto, and he had three anaphylactic reactions might have
      been caused by natto. Each event occurred 10 to 14 hours after he ate a meal
      containing natto. We performed detailed examinations to determine the allergen.
      First, the prick-by-prick tests with natto and its characteristic viscous yarn
      like surface were done and yielded positive results. Next, a provocation test
      with commercial natto (50 g) was performed and caused systemic eruption and
      pectoralgia about 9 hours after ingestion of the natto. The patients'plasma
      histamine level was elevated during the anaphylactic event. Anaphylaxis caused by
      natto was diagnosed. Recent studies have shown that the anaphylaxis caused by
      natto is of late-onset. Late-onset anaphylaxis can be considered one of IgE
      mediated allergic reactions. The viscous surface of natto contains poly-gamma
      glutamic acid (PGA). The hypothesized mechanism of late-onset anaphylaxis is
      delayed absorption or release of PGA into the bowel. In our case, the patient ate
      heated natto, we therefore speculate that suspect allergens were heat resistant.
      Patients with natto allergy must not eat natto, whether or not it is cooked or
      heated. Natto may induce allergic reactions up to a half-day after ingestion;
      thus, the clinical course and patient's diet must be considered during medical
      examination. Natto has recently gained popularity as a health food in foreign
      countries. The existence or natto allergy should be more widely recognized.

PMID- 16883112
TI  - An evaluation of the benefits of pulsatile versus nonpulsatile perfusion during
      cardiopulmonary bypass procedures in pediatric and adult cardiac patients.
AB  - The controversy over the benefits of pulsatile and nonpulsatile flow during
      cardiopulmonary bypass procedures continues. The objective of this investigation
      was to review the literature in order to clarify the truths and dispel the myths
      regarding the mode of perfusion used during open-heart surgery in pediatric and
      adult patients. The Google and Medline databases were used to search all of the
      literature on pulsatile vs. nonpulsatile perfusion published between 1952 and
      2006. We found 194 articles related to this topic in the literature. Based on our
      literature search, we determined that pulsatile flow significantly improved blood
      flow of the vital organs including brain, heart, liver, and pancreas; reduced the
      systemic inflammatory response syndrome; and decreased the incidence of
      postoperative deaths in pediatric and adult patients. We also found evidence that
      pulsatile flow significantly improved vital organ recovery in several types of
      animal models when compared with nonpulsatile perfusion. Several investigators
      have also shown that pulsatile flow generates more hemodynamic energy, which
      maintains better microcirculation compared with nonpulsatile flow. These results
      clearly suggest that pulsatile flow is superior to nonpulsatile flow during and
      after open-heart surgery in pediatric and adult patients.

PMID- 16883113
TI  - Development and early testing of a simple subcutaneous counterpulsation device.
AB  - The intra-aortic balloon pump has been widely and successfully used as a
      treatment for cardiac dysfunction, but it only has short-term applications. To
      overcome this limitation, a superficial counterpulsation device (CPD) is being
      developed to provide extended counterpulsation support to promote myocardial
      recovery. The CPD is a valveless, monoport, pneumatically driven, 40-ml sac that
      is intended to be implanted in a pacemaker-type pocket in the subclavian fossa.
      The sac is designed to fill in systole and empty during diastole through an
      outflow graft anastomosed to the subclavian artery. A feasibility study was
      conducted to investigate acute hemodynamic responses to the CPD in eight calves
      with diminished cardiac function. The CPD augmented aortic diastolic pressure,
      reduced left ventricular peak systolic and aortic ejection pressures by up to
      18%, and increased diastolic coronary flow by up to 21% and stroke volume by up
      to 12%. A cadaver fit study demonstrated that the human subclavian artery is a
      reasonable anastomosis site to consider and that the 40-ml CPD needs to be
      reduced in size to provide a better anatomical fit. The clinical attractiveness
      of this approach is that it may provide extended support through a subcutaneous
      surgical procedure.

PMID- 16883114
TI  - Replacement of the left-side valves of an implanted total artificial heart.
AB  - The MagScrew total artificial heart (TAH) is under development. Despite its
      anticipated durability and reliability, the possibility of a bioprosthetic valve
      malfunction exists. As a result, the potential for valve replacement surgery,
      instead of device replacement, would be desirable after a TAH implant. In two of
      our 90-day animal experiments, we successfully replaced the left-side valves
      through a left thoracotomy opposite to the right-sided incision site for the
      initial TAH implant. The results of these cases suggest that the left-side valves
      could also be replaced through a left thoracotomy approach in humans. To confirm
      the ability to access the left-side valves in humans, four human cadaver studies
      were performed with the use of a mock pump designed for human application. This
      report describes the operative techniques for left-side valve replacement in
      animals and discusses the advantages of a left thoracotomy in clinical
      situations, based on results from the human cadaver studies.

PMID- 16883115
TI  - Hemodynamic characteristics of a mixed flow pump prototype: progress report of in
      vitro and acute animal experiments.
AB  - A new dual-inlet mixed-flow blood pump was designed and tested in our laboratory.
      The objective of the present study was to analyze hemodynamic characteristics of
      the pump prototype in vitro and during acute in vivo experiments. The mixed-flow
      pump was first tested in vitro and then implanted in 11 pigs and 3 calves. The
      left ventricular apex was cannulated with the pump and an outflow graft was
      anastomosed to the descending thoracic aorta. Flow and pressure probes were also
      implanted. Animals were killed 3 to 12 hours after surgery. In 11 pigs, pump
      outflow averaged 3.8 +/- 0.4, 4.5 +/- 0.4, 5.2 +/- 0.8, 5.9 +/- 0.3, and 6.5
      l/min at 8,000, 9,000, 10,000, 11,000, and 12,000 pump speed in rpm. Differential
      pressure at the pump averaged 45 +/- 6, 54 +/- 8, 68 +/- 16, 70 +/- 12, and 85 +/
      7 mm Hg at 8,000, 9,000, 10,000, 11,000 and 12,000 rpm. Mean aortic pressure
      averaged 64 +/- 15 mm Hg throughout the procedures. In 3 calves, mean aortic
      pressure and left ventricular pressure remained stable during 4, 6, and 9 hours
      of support at 9,500, 10,000, 10,500, 11,000, and 11,500 rpm. The hemodynamic
      performance of our mixed-flow pump appears satisfactory during short-term support
      in animals. It supports similarly to axial-flow blood pumps in clinical trials.
      Based on these findings, an ameliorated design of this mixed-flow pump running at
      smaller rotational speed against a similar pressure head is under way.

PMID- 16883116
TI  - Ten-year NEDO BVAD development program: moving forward to the clinical arena.
AB  - Since 1995, the Baylor Group has been developing a totally implantable NEDO BVAD
      system. This 10-year program was completed in March 2005, and preparation for
      clinical trials is underway. This article summarizes the entire 10-year NEDO
      program and describes the strategy for clinical trials. The project aimed to
      achieve: (1) dual centrifugal pumps with the ability of full biventricular
      support, (2) a compact system implantable into small adults, (3) a totally
      implantable system with transcutaneous energy transmission system (TETS), (4) a
      durable system with a lifetime of over 5 years, and (5) a system free of thrombus
      and with minimal hemolysis. The final goals are to complete preclinical system
      evaluations and commence the clinical trials in the near future. In vitro studies
      have demonstrated a pump capacity of over 8.5 l/min and an Index of Hemolysis of
      <0.004 g/100 l. The pump-bearing life expectancy was over 5 years. To date, eight
      pumps endured in vivo studies of over 3 months without complications, including
      thromboembolic events. The in vitro endurance studies of eight pumps are longer
      than 1 year. There were no mechanical malfunctions or pump failure. A stepwise
      clinical trial is being planned: Step1, a wearable BVAD/VAD will be clinically
      studied; Step 2, the BVAD/VAD will be implanted intracorporeally without TETS;
      and, Step 3, a totally implantable system will be clinically evaluated. The NEDO
      BVAD system has completed preclinical testing. Clinical trial preparation is
      underway.

PMID- 16883117
TI  - Ventricular assist device implantation using a right thoracotomy.
AB  - Most patients needing implantation of a ventricular assist device (VAD) require
      repeated sternotomy; some after cardiac surgery, and others later for heart
      transplantation. The purpose of this study was to establish the right thoracotomy
      technique as an alternative for VAD implantation to reduce repeated sternotomy
      related morbidity and mortality. We performed a right thoracotomy in animals,
      preclinical cadaver fitting tests, and a clinical case. A total of 20 various
      animals underwent right thoracotomy for implantation of bi-VAD (BVAD, n = 17) and
      left VAD (LVAD, n = 3). The right chest cavity was entered through the fourth
      intercostal space with partial resection of the fifth rib. There was no procedure
      related morbidity or mortality, except for one calf with right anterior leg
      paralysis. Preclinical fitting tests were performed on 7 human cadavers to
      observe the anatomical feasibility of BVAD cannulation from the right side of the
      heart. In humans, the ascending aorta, interatrial groove, right atrium, and main
      pulmonary artery were identified as optimal cannula insertion sites for BVAD
      implantation. A patient with cardiogenic shock underwent a right thoracotomy for
      implantation of an external LVAD. Cardiac function recovered after 3 weeks, and
      the device was successfully explanted through a repeat right thoracotomy. In
      conclusion, a right thoracotomy can be an alternative method to the standard
      median sternotomy for patients who need repeated sternotomy because of previous
      cardiac surgery, transplantation at a later date, or those with mediastinal
      infections.

PMID- 16883118
TI  - Development of squeeze flow in mechanical heart valve: a particle image
      velocimetry investigation.
AB  - Fluid between the reducing flow channel of the valve occluder and the orifice
      wall tends to be squeezed out of the flow channel, causing a high-speed flow. The
      squeeze flow is accompanied by a sharp local pressure drop, which may result in
      potential cavitation phenomenon in a mechanical heart valve (MHV). Limited
      experimental investigation has been conducted into the flow physics of this
      squeeze flow phenomenon, which is likely to be the origin of MHV cavitation. We
      used a pulsatile test loop simulating physiologic flow conditions and an actual
      size transparent MHV model for flow visualization. A digital particle image
      velocimetry (DPIV) system incorporated with a microscope was applied to observe
      flow within a narrowing channel. A triggering mechanism was designed so that the
      DPIV system could be timed to capture images when the valve occluder was near its
      closing position. A series of images within the channel from 1.4 to 0.1 mm were
      captured. As the gap between the tip of the valve occluder and orifice wall
      becomes narrower, evidence of high-speed jet flow becomes more apparent. When the
      flow channel is reduced to around 0.1 mm, flow velocity of up to 2 m/s was noted.
      A sudden increase in high-speed jet flow causes a corresponding reduction in
      local pressure, and is a likely source for potential cavitation.

PMID- 16883119
TI  - Pharmacokinetics and the most suitable regimen of panipenem/beta mipron in
      critically ill patients receiving continuous renal replacement therapy: a pilot
      study.
AB  - Critically ill patients often have complications of acute renal failure induced
      by severe infection or sepsis. The patients need administration of broad-spectrum
      antibiotics as well as continuous renal replacement therapy (CRRT). However,
      there is no uniform pharmacokinetics of antibiotics during the CRRT because CRRT
      is performed with the various combinations of dialysate flows (QD) and
      ultrafiltrate flows (QF). The aims of this study were to estimate the
      pharmacokinetics of panipenem/beta Mipron (PAPM/BP) and to determine the
      appropriate treatment regimens for PAPM/BP in critically ill patients undergoing
      CRRT. In patients with CRRT, the PAPM total clearance (PAPM CLtot) was calculated
      as the sum of PAPM clearance dependent on the living body and CRRT and shown as
      follows:PAPM CLtot (ml/min) = (1.2 CLcre + 66.5) + 0.86 (QD + QF) where CLcre is
      creatinine clearance. Pharmacokinetic values of PAPM were measured in 4 patients
      with CRRT. According to these results, the most appropriate treatment regimen
      regarding PAPM CLtot (ml/min) showed as follows:PAPM CLtot < 80 0.5 g every 12
      hours or 1 g every 15 hoursPAPM CLtot 80 to 120 0.5 g every 8 hours or 1 g every
      12 hoursPAPM CLtot 120 to 160 0.5 g every 6 hours or 1 g every 8 hours.

PMID- 16883120
TI  - Dialyzer clearances and mass transfer-area coefficients for small solutes at low
      dialysate flow rates.
AB  - New daily hemodialysis therapies operate at low dialysate flow rates to minimize
      dialysate volume requirements; however, the dependence of dialyzer clearances and
      mass transfer-area coefficients for small solutes on dialysate flow rate under
      these conditions have not been studied extensively. We evaluated in vitro
      dialyzer clearances for urea and creatinine at dialysate flow rates of 40, 80,
      120, 160, and 200 ml/min and ultrafiltration flow rates of 0, 1, and 2 l/h, using
      a dialyzer containing PUREMA membranes (NxStage Medical, Lawrence, MA).
      Clearances were measured directly across the dialyzer by perfusing bovine blood
      with added urea and creatinine single pass through the dialyzer at a nominal
      blood flow rate of 400 ml/min. Limited, additional studies were performed with
      the use of dialyzers containing PUREMA membranes at a blood flow rate of 200
      ml/min and also with the use of other dialyzers containing polysulfone membranes
      (Optiflux 160NR, FMC-NA, Ogden, UT) and dialyzers containing Synphan membranes
      (NxStage Medical). For dialyzers containing PUREMA membranes, urea and creatinine
      clearances increased (p < 0.001) with increasing dialysate and ultrafiltration
      flow rates but were not different at blood flow rates of 200 and 400 ml/min.
      Dialysate saturation, defined as dialysate outlet concentration divided by blood
      water inlet concentration, for urea and creatinine was independent of blood and
      ultrafiltration flow rate but varied inversely (p < 0.001) with dialysate flow
      rate. Mass transfer-area coefficients for urea and creatinine were independent of
      blood and ultrafiltration flow rate but decreased (p < 0.001) with decreasing
      dialysate flow rate. Calculated mass transfer-area coefficients at low dialysate
      flow rates for all dialyzers tested were substantially lower than those reported
      by the manufacturers under conventional conditions. We conclude that dialyzers
      require specific characterization under relevant conditions if they are used in
      novel daily hemodialysis therapies at low dialysate flow rate.

PMID- 16883121
TI  - Comparison between two on-line reversed line position hemodialysis vascular
      access flow measurement techniques: saline dilution and thermodilution.
AB  - Periodical access flow measurements can predict the development and presence of
      vascular access flow-limiting stenosis and subsequent thrombosis. Access flow
      measurement has become a standard in vascular access care. Different techniques
      to measure access flow are available. The aim of this study was to compare an
      integrated access flow measurement device, based on thermodilution (Blood
      Temperature Monitor, BTM, Fresenius Medical Care, Bad Homburg, Germany), with the
      gold standard, the HD01 (Transonic Systems Inc., Ithaca, NY), whose technique is
      based on saline dilution. In 40 patients with end-stage renal disease, 40
      vascular accesses were studied to determine the correlation between access flow
      measurements by both techniques. Reproducibility of access flow measurements by
      both techniques was assessed in 20 patients on a weekly interval.A total of 40
      measurement series were performed. Average access flow measured with the saline
      technique and the thermodilution technique was 1053 (+/-495) ml/min and 1034 (+/
      527) ml/min, respectively (p = ns) (n = 40). Correlation between access flow
      measurements by both techniques expressed in R was 0.79 (r = 0.89).
      Reproducibility of saline and thermodilution subsequent measurements with a
      weekly interval, expressed in relative difference (Delta xrel) was 13 (+/-11)%
      and 24 (+/-14)%, respectively (p < 0.01) (n = 20).BTM access flow measurements
      correlated well with the HD01 access flow measurements. However, the better
      reproducibility of HD01 and shorter measurement time compared with BTM access
      flow measurements should be considered when implementing access flow measurement
      to prevent vascular access failure.

PMID- 16883122
TI  - Predilution versus postdilution during continuous venovenous hemofiltration: a
      comparison of circuit thrombogenesis.
AB  - During continuous venovenous hemofiltration, predilution can prolong circuit
      survival time, but the underlying mechanism has not been elucidated. The aim of
      the present study was to compare predilution with postdilution, with respect to
      circuit thrombogenesis. Eight critically ill patients were treated with both
      predilutional and postdilutional continuous venovenous hemofiltration in a
      crossover fashion. A filtration flow of 60 ml/min was used in both modes. We
      chose blood flows of 140 and 200 ml/min during predilution and postdilution,
      respectively, to keep the total flow through the hemofilter constant.
      Extracorporeal circuit pressures were measured hourly, and samples of blood and
      ultrafiltrate were collected at five different time points. Thrombin-antithrombin
      complexes and prothrombin fragments F1 + 2 were measured by ELISA, and platelet
      activation was assessed by flow cytometry. No signs of thrombin generation or
      platelet activation were found during either mode. During postdilution, baseline
      platelet count and maximal prefilter pressure had a linear relation, whereas both
      parameters were inversely related with circuit survival time. In summary,
      predilution and postdilution did not differ with respect to extracorporeal
      circuit thrombogenesis. During postdilution, baseline platelet count and maximal
      prefilter pressure were inversely related with circuit survival time.

PMID- 16883123
TI  - Extravascular lung water and peripheral volume status in hemodialysis patients
      with and without a history of heart failure.
AB  - Determining volume status in hemodialysis patients with a history of congestive
      heart failure (CHF) is difficult. Extravascular lung water (EVLW) may be derived
      from blood ultrasound velocity changes following injections of 0.9% and 5%
      saline. Bioimpedance spectroscopy can measure total body water (TBW) and its
      intracellular fluid (ICF) and extracellular fluid (ECF) compartments. We studied
      29 clinically euvolemic hemodialysis patients, 12 of whom had a history of CHF.
      The ECF and ICF were measured before dialysis, and EVLW was measured during
      dialysis. Values of EVLW were similar between patients without CHF and those with
      CHF (3.55 ml/kg +/- 0.94 SD versus 3.88 ml/kg +/- 0.82 SD, respectively; p = NS).
      The ECF/ICF ratio was higher among patients with a history of CHF (1.27 +/- 0.29)
      than among those without such a history (1.04 +/- 0.04; p < 0.05), indicating
      that ECF volume overload was present in both groups, but was higher in those with
      a CHF history. There was a positive correlation between EVLW and ECF/ICF ratios
      (r = 0.54, p < 0.01). Measurements of EVLW were higher in two pulmonary edema
      patients ((7.95 ml/kg and 5.95 ml/kg; p < 0.05). The results of this study
      suggest that 1) hemodialysis patients with a history of CHF have more ECF volume
      overloaded than those without such a history; 2) the degree of ECF expansion is
      associated with increasing EVLW volume, even in patients without pulmonary edema;
      and 3) ECF volume expansion eventually exceeds limits and pulmonary edema occurs.
      These developing technologies of volume measurement may be of value in this
      challenging clinical area.

PMID- 16883124
TI  - Determining lung water volume in stable hemodialysis patients.
AB  - Lung water (LW) reflects the water content of the lung interstitium. Because
      hemodialysis patients have expanded total body water (TBW) they may also have
      increased LW. Hypertonic saline promotes a flux of water from lung to blood,
      which is measured by ultrasound flow probes on hemodialysis tubing. The volume of
      flux is an indirect measure of LW. Our purpose was to determine the feasibility
      and reproducibility of LW derived with ultrasound velocity dilution, to determine
      the effect of ultrafiltration on LW in stable hemodialysis patients, and to
      compare changes in LW with fluid compartment shifts using bioimpedance. Lung
      water, cardiac output, total body water, and extracellular and intracellular
      fluid volumes were measured in 24 stable hemodialysis patients at the beginning
      of hemodialysis and after ultrafiltration. The LW values at the beginning of
      hemodialysis (298.8 +/- 90.2 ml or 3.67 +/- 1.47 ml/kg) fell during hemodialysis
      (250.8 +/- 55.8 ml or 3.12 +/- 0.96 ml/kg; p < 0.05), as did TBW and
      extracellular fluid volumes (p < 0.001). Cardiac output, cardiac index, and
      central blood volume also decreased significantly with ultrafiltration (p <
      0.005, p < 0.005, and p < 0.01, respectively). Results showed that stable
      hemodialysis patients have higher specific LW values (3.67 ml/kg) than the normal
      population (2 ml/kg) and ultrafiltration produces a significant decline in LW
      values.

PMID- 16883125
TI  - Leukocytes-depleting filters preferentially remove activated leukocytes and
      reduce the expression of surface adhesion molecules during the simulated
      extracorporeal circulation of human blood.
AB  - The effect of leukocyte-depleting filters on the total and activated leukocyte
      counts and the expression of surface adhesion molecules CD11b, CD18, and CD62L
      during the in vitro extracorporeal circulation of human blood was studied. A 200
      ml blood sample was taken from 10 patients undergoing CABG surgery. The blood was
      circulated for 60 minutes within an experimental extracorporeal circuit. A
      leukocyte-depleting filter was attached in five circuits (filtered group). In
      five other circuits, no filter was used (controls). Total leukocyte counts were
      determined manually. Activated leukocytes were identified using nitroblue
      tetrazolium staining. The expression of CD11b, CD18, and CD62L was measured with
      flow cytometry. At 60 minutes, total leukocyte counts were reduced by 49% from
      the baseline values in the filtered group and 10% in the control group (p <
      0.0001). Activated leukocyte counts decreased by 86% in the filtered group and
      increased by 116% in the control group (p < 0.0001). In the filtered group, the
      expression of CD11b, CD18, and CD612L decreased by 60%, 21%, and 79%,
      respectively, and in the control group it increased by 24%, 6%, and 28% (p <
      0.0001). Leukocyte-depleting filters preferentially remove activated leukocytes
      and reduce the expression of CD11b, CD18, and CD62L during the in vitro
      extracorporeal circulation of human blood.

PMID- 16883126
TI  - Regional referral system for patients with acute mechanical support: experience
      at the Cleveland Clinic Foundation.
AB  - Regional referral networks ("hub and spoke") have been created to facilitate the
      transfer of patients on mechanical circulatory support. Although individual
      centers report good success, overall outcomes have remained poor. We investigated
      whether preoperative variables influenced survival and could be used to help
      select patients best served by referral. A retrospective chart review was
      conducted on all patients transferred to our institution supported on cardiac
      assist devices. Between January 1995 and September 2003, 39 patients were
      received in transfer for continued care after the implantation of a cardiac
      assist device. Eighty-five percent of patients had the ABIOMED BVS 5000
      implanted. The most common indication was postcardiotomy shock. Sixty-four
      percent of patients were not candidates for heart transplantation due to medical
      or social contraindications. The 30-day mortality of this group was 62%.
      Survivors had less comorbidity and were less likely to have complex surgeries,
      neurologic impairment, and multisystem organ failure when presenting to our
      center. Devices were weaned in 30% of cases. Only six patients (15%) were
      successfully transplanted, and five of these patients have done well at follow
      up. Based on our experience, we believe that cardiogenic shock patients benefit
      from a regional referral system if they have not had complex cardiac surgical
      procedures or developed multisystem organ failure. Furthermore, there is a
      survival advantage when using long-term devices because this allows possible
      recovery or transplantation.

PMID- 16883127
TI  - Evaluation of compliance and stiffness of decellularized tissues as scaffolds for
      tissue-engineered small caliber vascular grafts using intravascular ultrasound.
AB  - This study evaluated the compliance and stiffness of decellularized canine common
      carotid artery as well as decellularized canine ureter and compared it with that
      of polytetrafluoroethylene, elastin gel combined with polylactic acid tube, and
      canine common carotid artery. To calculate the compliance and stiffness, internal
      diameters and cross-sectional areas were measured according to changes in the
      intraluminal pressures using intravascular ultrasound in a closed circuit system
      equipped with a syringe pump. The pressure-area curve, stiffness parameter beta,
      and diameter compliance were evaluated. Canine common carotid artery and
      decellularized canine common carotid artery, as well as decellularized canine
      ureter, showed a compliant response, a J-shaped curve. However, the latter
      evidenced different characteristics in the low pressure range. Although the cross
      sectional area of the elastin gel combined with polylactic acid tube showed some
      changes, it did not present a J-shape curve. Polytetrafluoroethylene exhibited a
      noncompliant response.The results in this study have shown that the compliance in
      the decellularized matrices was maintained after cell extraction, which
      demonstrated the importance of the remaining matrix structure in the mechanical
      properties of decellularized tissue. A clear difference between the
      decellularized matrices and synthetic materials was noted in terms of the
      compliance, even in materials composed of relatively elastic materials.

PMID- 16883128
TI  - Photolytically driven generation of dissolved oxygen and increased oxyhemoglobin
      in whole blood.
AB  - The severely debilitating nature of chronic lung disease has long provided the
      impetus for the development of technologies to supplement the respiratory
      capacity of the human lung. Although conventional artificial lung technologies
      function by delivering pressurized oxygen to the blood through a system of hollow
      fibers or tubes, our approach uses photolytic energy to generate dissolved oxygen
      (DO) from the water already present in blood, thus eliminating the need for gas
      delivery. We have previously demonstrated that it is feasible to generate
      dissolved oxygen from water based on UVA illumination of a highly absorbent TiO2
      thin film. In the current study, we extend this work by using photolytic energy
      to generate DO from whole blood, thus resulting in an increase of oxyhemoglobin
      as a function of back side TiO2 surface film illumination. Initial experiments,
      performed with Locke's Ringer solution, demonstrated effective film thickness and
      material selection for the conductive layer. The application of a small bias
      voltage was used to conduct photogenerated electrons from the aqueous phase to
      minimize electron recombination with the DO.Mixed arterial-venous bovine blood
      was flowed in a recirculating loop over TiO2 nanocrystalline films illuminated on
      the side opposite the blood (or "back side") to eliminate the possibility of any
      direct exposure of blood to light. After light exposure of the TiO2 film, the
      fraction of oxyhemoglobin in the blood rapidly increased to near saturation and
      remained stable throughout the trial period. Last, we evaluated potential
      biofouling of the DO generating surface by scanning electron microscopy, after
      photolytically energized DO generation in whole blood, and observed no white or
      red blood cell surface deposition, nor the accumulation of any other material at
      this magnification. We conclude that it is feasible to photolytically oxygenate
      the hemoglobin contained in whole blood with oxygen derived from the blood's own
      water content without involving a gaseous phase.

PMID- 16883129
TI  - Percutaneous venovenous CO2 removal with regional anticoagulation in an ovine
      model.
AB  - Extracorporeal CO2 removal may reduce minute ventilation requirements and allow
      for better tolerance of low tidal volume ventilating strategies in patients with
      severe respiratory insufficiency. Conventional extracorporeal gas exchange is
      labor-intensive, expensive, and usually requires systemic anticoagulation. In
      this study, a simplified venovenous circuit was developed by using regional
      citrate anticoagulation to avoid potential complications associated with systemic
      heparin. Five healthy adult sheep underwent percutaneous placement of a double
      lumen 18F catheter into the internal jugular vein. The extracorporeal circuit
      consisted of a hollow fiber oxygenator and a variable speed roller pump. Regional
      anticoagulation consisted of a continuous citrate infusion to the inflow limb of
      the circuit. Systemic calcium levels were maintained by calcium chloride infusion
      through a central line. CO2 transfer was measured at varying levels of blood and
      gas flow. CO2 transfer ranged from 31 ml/min (500 ml/min blood flow; 2 l/min gas
      flow) to 150 ml/min (1000 ml/min blood flow; 15 l/min gas flow) and was directly
      proportional to blood flow and gas flow (p < 0.05). Normocapnia was maintained
      despite a 75% reduction in minute ventilation. At 24 hours, there was no
      significant clot formation in the circuit.

PMID- 16883130
TI  - Hemodynamic guidelines for design and control of a turbodynamic pediatric
      ventricular assist device.
AB  - The design of mechanical circulatory support devices typically requires a priori
      knowledge of the hemodynamic requirements of their intended use. These
      requirements are difficult to determine because of limited clinical experience.
      This is especially true for the pediatric population, for whom there is a dearth
      of longitudinal data. This report aims to provide both engineers and physicians
      with benchmarks for determining the optimal flow requirements and settings for
      pediatric ventricular assist devices that are currently being developed. Criteria
      were developed on the basis of estimates derived from various sources. The
      potential patient population was estimated by using the prevalence of children on
      the heart transplant waiting list and those placed on extracorporeal membrane
      oxygenation. Cardiac outputs were determined for individual weights and body
      surface areas, using published values for healthy and sick pediatric patients.
      The recommended pump range was optimized to include the most patients, while
      considering the design constraints. This study identifies a significant
      population of patients who would benefit from a device providing 0.52 to 1.92
      l/min.

PMID- 16883131
TI  - Dialysis for thiocyanate intoxication: a case report and review of the
      literature.
AB  - Limited data are available on the use of dialysis to treat cyanide or thiocyanate
      intoxication. This report describes the case of a 65-year-old woman with renal
      insufficiency who had development of thiocyanate toxicity secondary to a
      nitroprusside infusion. A rapid decline in her blood thiocyanate level was
      observed in response to initiation of continuous venovenous hemodiafiltration.

PMID- 16883132
TI  - Abstracts of the 5th European Symposium on Perfluorocarbon (PFC) Application and
      Liquid Ventilation, March 17-18, 2006, Milano, Italy.

PMID- 16883145
TI  - Exercise as an augmentation strategy for treatment of major depression.
AB  - The use of augmentation strategies among patients with major depression is
      increasing because rates of complete remission with standard antidepressant
      monotherapy are quite low. Clinical and neurobiological data suggest that
      exercise may be a good candidate for use as an augmentation treatment for
      depression. This pilot study examined the use of exercise to augment
      antidepressant medication in patients with major depression. Seventeen patients
      with incomplete remission of depressive symptoms began a 12-week exercise program
      while continuing their antidepressant medication (unchanged in type or dose).
      Individual exercise prescriptions were calculated based on an exercise dose
      consistent with currently recommended public health guidelines. The exercise
      consisted of both supervised and home-based sessions. The 17-item Hamilton Rating
      Scale for Depression (HRSD17) and the Inventory of Depressive Symptomatology-Self
      Report (IDS-SR30) were used to assess symptoms of depression on a weekly basis.
      Intent-to-treat analyses yielded significant decreases on both the HRSD17 (5.8
      points, p < 0.008) and IDS-SR30 (13.9 points, p < 0.002). For patients who
      completed the study (n = 8), HRSD17 scores decreased by 10.4 points and IDS-SR30
      scores decreased by 18.8 points. This study provides preliminary evidence for
      exercise as an effective augmentation treatment for antidepressant medication.
      This is a lower-cost augmentation strategy that has numerous health benefits and
      may further reduce depressive symptoms in partial responders to antidepressant
      treatment. Practical tips on how practitioners can use exercise to enhance
      antidepressant treatment are discussed. Longer-term use of exercise is also
      likely to confer additional health benefits for this population.

PMID- 16883146
TI  - A comparison of divalproex and oxcarbazepine in aggressive youth with bipolar
      disorder.
AB  - BACKGROUND: Divalproex (DVP) and oxcarbazepine (OXC) are used to treat pediatric
      bipolar disorder (PBPD) with severe aggression but these agents have not been
      compared in head to head trials. METHODS: Electronic medical records were
      reviewed for those (age < 18) who received DVP (n = 20) or OXC (n = 11) for the
      treatment of PBPD with severe aggression. Change in prospectively rated Clinical
      Global Impressions-Severity (CGI-S) scores that measured global improvement of
      mental illness from baseline and rates of discontinuation due to adverse effects
      at approximately 4 months were the primary outcomes. CGI-S specific to aggression
      (CGI-Ag-S), which was rated retrospectively and blinded to treatment, was a
      secondary outcome. RESULTS: Greater reduction in CGI-S scores occurred with DVP
      compared with OXC at 4 months (p = 0.007). Both CGI-S and CGI-Ag-S scores
      improved significantly from baseline to the 4-month timepoint with DVP but not
      OXC. There were no significant differences in weight changes between the groups.
      Rates of discontinuation due to adverse events were similar. However, more
      discontinuations due to worsening aggression occurred with OXC (DVP 0%, OXC
      27.3%, p = 0.037). More patients receiving DVP had a decrease of 1 point or more
      on the CGI-S and had not discontinued due to adverse events as of the patient's
      last recorded visit on the index medication (DVP 13 (65%), OXC 2 (18%), p =
      0.023). CONCLUSIONS: OXC appeared less effective than DVP for PBPD with
      aggression in this study. Limitations included the small sample size and the
      open, nonrandomized, retrospective study design. Future prospective, double-blind
      studies are warranted to determine the place of OXC in the treatment of PBPD.

PMID- 16883147
TI  - A pilot, open-label safety study of quetiapine for treatment of moderate
      psychotic agitation in the emergency setting.
AB  - OBJECTIVE: The goal of this pilot study was primarily to explore the safety and,
      secondarily, the efficacy of the use of "prn" quetiapine for treatment of
      moderate agitation accompanied by psychosis in an emergency department setting.
      METHODS: This was an open-label study in which 20 patients with psychotic
      agitation were treated in the emergency department with 100, 150, or 200 mg of
      quetiapine. Physicians who were unaffiliated with the study established the
      diagnoses and selected the doses to be used for each patient. A rater who was
      blinded to the dose performed the assessments. The primary safety measure was the
      onset of orthostatic hypotension. The primary efficacy measure was a 40%
      reduction in scores on the Positive and Negative Syndrome Scale-Excited Component
      (PANSS-EC) over 120 minutes. The secondary efficacy measure was a reduction of 2
      points or more on the Behavioral Activity Rating Scale (BARS) at 120 minutes post
      dose. All subjects provided written informed consent. RESULTS: With regard to
      safety outcomes, 40% of subjects exhibited orthostasis by 120 minutes, although
      only 25% of these patients described clinically significant symptoms. In terms of
      efficacy, 50% of subjects experienced at least a 40% reduction in PANSS-EC scores
      at 2 hours, while 68.8% showed reductions of 2 points or more in scores on the
      BARS over the same time period. CONCLUSION: Quetiapine demonstrated some efficacy
      as a sedative agent in the emergency setting, although no clear dose-response
      pattern emerged over the narrow dose range tested. Orthostasis was common and did
      not correlate with dosing. This small study did not support the use of quetiapine
      to treat acute agitation in potentially volume-depleted patients.

PMID- 16883148
TI  - Searching for new options for treating insomnia: are melatonin and ramelteon
      beneficial?
AB  - Insomnia is one of the most common complaints faced in clinical practice. The
      limited pharmacological options available make the treatment of this complaint a
      challenge. All of the available benzodiazepines and non-benzodiazepine hypnotics
      have the potential to induce addiction, cause withdrawal symptoms, or trigger
      rebound insomnia. Further, the evidence supporting the utility of commonly
      prescribed options such as antidepressants and antipsychotics is limited.
      Melatonin is a hormone that has been associated with soporific effects. Based on
      this premise, a melatonin receptor agonist was created. Ramelteon was approved by
      the Food and Drug Administration in 2005 and is the only medication indicated for
      the long-term treatment of insomnia. A critical review with a clinical
      perspective of randomized, placebo-controlled clinical trials was conducted to
      determine the efficacy of melatonin and ramelteon for the treatment of insomnia.
      Based on this review, it appears that more placebo-controlled trials are
      indicated before valid judgments concerning the efficacy of both melatonin and
      ramelteon can be made. In the meantime, there is some support for the use of
      melatonin for the treatment of insomnia, and findings concerning ramelteon also
      appear promising. Nevertheless, clinicians who prescribe melatonin or ramelteon
      should be cautious and carefully monitor both potential benefits and adverse
      effects, since data on melatonin are based on studies with multiple limitations
      and only three controlled trials have been done with ramelteon.

PMID- 16883149
TI  - Clinically relevant pharmacology of neuropsychiatric drugs approved over the last
      three years: part I.

PMID- 16883150
TI  - Putting your medical record on the line.

PMID- 16883151
TI  - Atypical antipsychotics: a case study in new era risk management.

PMID- 16883152
TI  - Neuroleptic malignant syndrome: a case report.

PMID- 16883153
TI  - Chronic recurrent subarachnoid hemorrhage from a trigeminal nerve malignant
      peripheral nerve sheath tumor: case report.
AB  - OBJECTIVE: Clinically significant intratumoral or peritumoral bleeding from
      trigeminal nerve tumors is very rare. CLINICAL PRESENTATION: We report the case
      of a 59-year-old man who presented with recurrent subarachnoid hemorrhage from a
      left trigeminal nerve malignant peripheral nerve sheath tumor. He presented with
      decreased consciousness, left facial hypesthesia, and left facial weakness.
      Trigeminal neuralgia was present for 18 months. Cranial computed tomographic and
      magnetic resonance imaging scans revealed a left parapontine mass with cystic
      changes and intratumoral bleeding. Furthermore, signs of hemosiderosis of the
      subarachnoid space were noted. Lumbar puncture revealed fresh bleeding.
      Angiography detected no aneurysm or other causes of bleeding. The patient became
      fully alert within hours, the facial weakness improved within a few days. There
      was no evidence of vasospasm or persisting hydrocephalus. He underwent left-sided
      suboccipital craniotomy for macroscopically total tumor removal. INTERVENTION:
      The patient underwent total tumor removal via a left suboccipital approach.
      Intraoperatively, evidence of recurrent intratumoral bleeding was noted.
      Histological examination revealed a malignant peripheral nerve sheath tumor
      (World Health Organization Grade III). Postoperatively, the hypesthesia improved
      significantly. The patient was transferred to radiotherapy for external beam
      radiation. CONCLUSIONS: This is the first report regarding a malignant peripheral
      nerve sheath tumor of the trigeminal nerve that caused clinically significant
      subarachnoid hemorrhage caused by intratumoral bleeding.

PMID- 16883154
TI  - Adamantinoma of the spine: case report.
AB  - OBJECTIVE: We report a patient with a cervicothoracic spinal and a mandibular
      adamantinoma. Adamantinoma is a rare malignant neoplasm of bone and, to our
      knowledge, there have been only five cases of spinal adamantinoma reported. The
      pathogenesis of the adamantinoma, as well as the management of this extremely
      rare spinal tumor, is reviewed. CLINICAL PRESENTATION: A 55-year-old man was
      admitted to our service with cervical pain and signs of C8 and T1 radiculopathy.
      On physical examination, cervical spine deformity, swelling in the left mandible
      region, and signs of C8 and T1 radiculopathy were observed. Neuroradiology
      examinations showed an osteolytic mass of the C6, C7, and T1 vertebral bodies,
      extending into the lateral masses and transverse processes. After surgical
      procedures, the patient had clinical improvement. INTERVENTION: Corpectomy of C6,
      C7, and T1 was performed through a cervicothoracic anterior approach. Anterior
      stabilization of the spine was obtained using an autologous iliac crest graft and
      osteosynthesis with an anterior plate. On a second procedure, posterior tumor
      resection and spinal stabilization were performed. After the 1-year follow-up
      examination, a new anterior procedure was performed because of tumor recidivity
      and spine instability. CONCLUSION: Adamantinoma, an extremely rare lesion, is a
      locally aggressive tumor with slow growth and the potential to metastasize.
      Although it is an extremely rare occurrence in the spine, adamantinoma should be
      considered on the diagnosis of tumors of the vertebrae. Neuroradiological
      examinations are not specific in the differentiation of this tumor from other
      conditions. This fact, coupled with the limited experience that most physicians
      in general have in dealing with this tumor, makes the diagnosis and treatment of
      adamantinoma challenging.

PMID- 16883156
TI  - Estimating the hemodynamic impact of interventional treatments of aneurysms:
      numerical simulation with experimental validation: technical case report.
AB  - OBJECTIVE: The goal of this study was to use phase-contrast magnetic resonance
      imaging and computational fluid dynamics to estimate the hemodynamic outcome that
      might result from different interventional options for treating a patient with a
      giant fusiform aneurysm. METHODS: We followed a group of patients with giant
      intracranial aneurysms who have no clear surgical options. One patient
      demonstrated dramatic aneurysm growth and was selected for further analysis. The
      aneurysm geometry and input and output flow conditions were measured with
      contrast-enhanced magnetic resonance angiography and phase-contrast magnetic
      resonance imaging. The data was imported into a computational fluid dynamics
      program and the velocity fields and wall shear stress distributions were
      calculated for the presenting physiological condition and for cases in which the
      opposing vertebral arteries were either occluded or opened. These models were
      validated with in vitro flow experiments using a geometrically exact silicone
      flow phantom. RESULTS: Simulation indicated that altering the flow ratio in the
      two vertebrals would deflect the main blood jet into the aneurysm belly, and that
      this would likely reduce the extent of the region of low wall shear stress in the
      growth zone. CONCLUSIONS: Computational fluid dynamics flow simulations in a
      complex patient-specific aneurysm geometry were validated by in vivo and in vitro
      phase-contrast magnetic resonance imaging, and were shown to be useful in
      modeling the likely hemodynamic impact of interventional treatment of the
      aneurysm.

PMID- 16883155
TI  - Intramedullary endometriosis of the conus medullaris: case report.
AB  - OBJECTIVE: Intraspinal endometriosis is an extremely rare condition with
      characteristic symptoms, including lower back pain that increases in severity
      during each menstrual cycle. METHODS: Here, we report a case of endometriosis
      involving the conus cauda region. This patient presented with acute deterioration
      secondary to hemorrhage. We also review the relevant literature. RESULTS:
      Magnetic resonance imaging scans of the dorsolumbar region showed a mass lesion
      within the spinal canal at the L1-L2 level with evidence of acute hemorrhage. The
      patient underwent an emergency D12-L2 laminectomy and microdecompression of the
      lesion. The histological and immunohistochemical features were characteristic of
      intraspinal endometriosis. CONCLUSION: Intraspinal endometriosis must be
      recognized as a potential cause of periodic neurological signs and symptoms in
      young and middle-aged women.

PMID- 16883157
TI  - Preoperative embolization of hypervascular spinal metastases using percutaneous
      direct injection with n-butyl cyanoacrylate: technical case report.
AB  - OBJECTIVE: Intraoperative blood loss constitutes a major cause of perioperative
      morbidity in surgical decompression and reconstruction of highly vascular spinal
      metastatic tumors. We propose a technique for embolization of highly vascular
      vertebral metastases using percutaneous direct injection using n-butyl
      cyanoacrylate (NBCA) instead of polymethylmethacrylate to complement preoperative
      transarterial embolization and to minimize operative blood loss. METHODS: Five
      patients with renal cell carcinoma metastases to the spine (one cervical, one
      thoracic, and three lumbar) underwent embolization by percutaneous direct
      injection of the affected vertebrae with a mixture of NBCA and iodized oil to
      supplement transarterial embolization with polyvinyl alcohol particles and
      fibered platinum coils. This was achieved via a transpedicular approach in four
      cases and by direct vertebral body puncture in one case. RESULTS: The
      percutaneous NBCA direct injection procedure was technically successful in all
      cases and was not associated with neurological or medical complications. All
      patients underwent subsequent vertebrectomy and spinal instrumentation. Surgical
      resection was performed with lower than expected blood loss and with a subjective
      improvement in tumor tissue handling and dissection. CONCLUSION: The extent of
      tumor devascularization can be improved by supplementing transarterial
      embolization with NBCA direct injection to decrease operative blood loss and
      increase the safety of surgical resection and stabilization of highly vascular
      spinal metastases.

PMID- 16883158
TI  - Surgifoam and mitoxantrone in the glioblastoma multiforme postresection cavity:
      the first step of locoregional chemotherapy through an ad hoc-placed catheter:
      technical note.
AB  - OBJECTIVE: To investigate the safety and feasibility of a novel form of treatment
      offered by the direct intraoperative application of a Surgifoam-mitoxantrone mix
      into a glioblastoma multiforme postresection cavity. A technique for the
      placement of an intracavity catheter connected with a subcutaneous reservoir for
      further locoregional mitoxantrone administration is also described. METHODS:
      Between January and December 2004, 22 consecutive recurrent glioblastoma
      multiforme patients (14 men, 8 women; age, 56-72 yr; average, 64 yr; median, 65
      yr) were enrolled in this study. All patients underwent image-assisted gross
      total resection of the pathological tissue. A Surgifoam-mitoxantrone mix (1 g
      Surgifoam powder, 3 ml physiological solution, and 12 mg mitoxantrone in 6 ml)
      was used to fill the surgical cavity. A ventricular catheter, connected to a
      Rickham subcutaneous reservoir, was then positioned in the surgical cavity for
      future mitoxantrone administration. RESULTS: Toxic effects caused by mitoxantrone
      administration were not observed in any patients during the first postoperative
      month. On postoperative Days 1, 7, and 30, computed tomographic scans excluded
      surgical complications. In three patients, residual tumor was disclosed.
      CONCLUSION: A mix of Surgifoam and mitoxantrone could be safely applied
      intraoperatively into the post-glioblastoma multiforme resection cavity without
      any observable side effects. This technique may benefit both the surgeon and the
      patient by taking advantage of the drug's hemostatic and cytostatic properties.

PMID- 16883162
TI  - Hyponatremia in the neurosurgical patient: epidemiology, pathophysiology,
      diagnosis, and management.
AB  - OBJECTIVE: Hyponatremia is an important and common electrolyte disorder in
      critically ill neurosurgical patients that has been reported in association with
      a number of different primary diagnoses. The correct diagnosis of the
      pathophysiological cause is vital because it dramatically alters the treatment
      approach. METHODS: We review the epidemiology and presentation of patients with
      hyponatremia, the pathophysiology of the disorder with respect to sodium and
      fluid balance, and the diagnostic procedures for determining the correct cause.
      RESULTS: We then present the various treatment options, including discussion of
      one of the newest groups of agents, the arginine vasopressin receptor
      antagonists, currently under study for the treatment of hyponatremia in
      neurosurgical patients. CONCLUSION: Hyponatremia is a serious comorbidity in
      neurosurgical patients that requires particular attention as its treatment varies
      by cause and its consequences can affect neurological outcome.

PMID- 16883163
TI  - Patient outcome at long-term follow-up after aggressive microsurgical resection
      of cranial base chordomas.
AB  - OBJECTIVE: In this study, we evaluated patients' clinical outcome and recurrence
      rates at long-term follow-up after aggressive microsurgical resection of cranial
      base chordomas. METHODS: Seventy-four patients with chordomas underwent
      operations during a 16-year period from 1988 to 2004. The philosophy was to
      perform complete resection whenever possible and to provide adjuvant radiotherapy
      for remnants. Staged operations were performed for extensive tumors or if a
      sizable tumor remnant was noted after the first resection. Patients included
      primary (previously untreated) and previously operated or irradiated cases.
      Information was prospectively gathered concerning the patients' neurological
      condition, Karnofsky Performance Scale score, and tumor status on magnetic
      resonance imaging scans. RESULTS: There were 47 primarily operated patients
      (63.5%) and 27 patients (36.5%) who had previously undergone surgery or
      radiotherapy. A total of 121 procedures were performed in 74 patients. The mean
      follow-up period was 96 months, with a range of 1 to 198 months. A single stage
      removal was performed in 41 (55.4%) of the patients and multiple stage removal
      was performed in 33 (44.5%) of the patients. Gross total removal was accomplished
      in 53 (71.6%) of the patients, and subtotal resection was accomplished in 21
      (28.4%) of the patients. During the follow-up period, 24 (32%) of the patients
      had no evidence of disease, 37 (50%) of the patients were alive with evidence of
      disease, 11 (14.8%) of the patients died of disease, and two (2.7%) of the
      patients died of complications. Recurrence-free survival at 10 years was 31% for
      the whole group, 42% for the primarily operated patients, and 26% for the
      reoperation cases (P = 0.0001). The average Karnofsky Performance Scale score was
      80 +/- 11.7 preoperatively, 84 +/- 8.9 at the 1-year follow-up, and 86 +/- 12.8
      at the last follow-up in surviving patients. No conclusion could be drawn
      regarding the value of radiotherapy because of the treatment philosophy and the
      small number of patients. CONCLUSION: Aggressive microsurgical resection of
      chordomas can be followed by long-term, tumor-free survival with good functional
      outcome. A more conservative strategy is recommended in reoperation cases,
      especially after previous radiotherapy, to reduce postoperative complications.

PMID- 16883164
TI  - Surgically treated tuberculum sellae and diaphragm sellae meningiomas: the
      importance of short-term visual outcome.
AB  - OBJECTIVE: The visual outcome in patients with tuberculum and diaphragm sellae
      meningiomas treated with microsurgery was evaluated. Prognostic and diagnostic
      values of short- and long-term postoperative visual outcome and etiology for
      postoperative visual deterioration are discussed with special attention. METHODS:
      Clinical data for 30 surgically treated patients with tuberculum and diaphragm
      sellae meningiomas were reviewed retrospectively. The mean duration of the follow
      up period was 75.9 months (range, 12-151 mo). Mean tumor diameter and volume was
      25.9 mm (range, 16.3-63.3 mm) and 12.4 cm (range, 2.3-125.6 cm). A visual
      impairment score was used to assess the short-term (< or =2 wk after surgery) and
      the long-term (>6 mo after surgery) postoperative visual outcome. Various
      predictive factors for visual outcome were tested statistically. RESULTS:
      Complete resection was achieved in 23 out of 30 (76.7%) patients. Average
      preoperative, short- and long-term visual impairment scores were 48.2, 43.4, and
      40.9, respectively. Favorable visual outcome was achieved in 80% of patients in
      the short term and 70% in the long term. Short-term postoperative aggravation of
      visual function was an ominous sign of further aggravation or at least of little
      hope for recovery, whereas there was a tendency to improve in the long term if
      short-term postoperative visual function showed favorable outcome. Recurrence or
      regrowth of tumor fully was responsible for late deterioration of visual
      function. No significant prognostic factor for visual outcome could be found.
      CONCLUSION: Short-term postoperative visual outcome was a strong indicator of
      permanent visual outcome after surgery for tuberculum sellae and diaphragm sellae
      meningiomas.

PMID- 16883165
TI  - Visual field preservation after multisession cyberknife radiosurgery for
      perioptic lesions.
AB  - OBJECTIVE: The restricted radiation tolerance of the anterior visual pathways
      represents a unique challenge for ablating adjacent lesions with single-session
      radiosurgery. Although preliminary studies have recently demonstrated that
      multisession radiosurgery for selected perioptic tumors is both safe and
      effective, the number of patients in these clinical series was modest and the
      length of follow-up limited. The current retrospective study is intended to help
      address these shortcomings. METHODS: Forty-nine consecutive patients with
      meningioma (n = 27), pituitary adenoma (n = 19), craniopharyngioma (n = 2), or
      mixed germ cell tumor (n = 1) situated within 2 mm of a "short segment" of the
      optic apparatus underwent multisession image-guided radiosurgery at Stanford
      University Medical Center. Thirty-nine of these patients had previous subtotal
      surgical resection, and six had previously been treated with conventional
      fractionated radiotherapy (6). CyberKnife radiosurgery was delivered in two to
      five sessions to an average tumor volume of 7.7 cm3 and a cumulative average
      marginal dose of 20.3 Gy. Formal visual testing and clinical examinations were
      performed before treatment and at follow-up intervals beginning at 6 months.
      RESULTS: After a mean visual field follow-up of 49 months (range, 6-96 mo),
      vision was unchanged postradiosurgery in 38 patients, improved in eight (16%),
      and worse in three (6%). In each instance, visual deterioration was accompanied
      by tumor progression that ultimately resulted in patient death. However, one of
      these patients, who had a multiply recurrent adrenocorticotropic hormone
      secreting pituitary adenoma, initially experienced early visual loss without
      significant tumor progression after both a previous course of radiotherapy and
      three separate sessions of radiosurgery. After a mean magnetic resonance imaging
      follow-up period of 46 months, tumor volume was stable or smaller in all other
      cases. Two patients died of unrelated nonbrain causes. CONCLUSION: Multisession
      radiosurgery resulted in high rates of tumor control and preservation of visual
      function in this group of perioptic tumors. Ninety-four percent of patients
      retained or improved preradiosurgical vision. This intermediate-term experience
      reinforces the findings from earlier studies that suggested that multisession
      radiosurgery can be a safe and effective alternative to either surgery or
      fractionated radiotherapy for selected lesions immediately adjacent to short
      segments of the optic apparatus.

PMID- 16883166
TI  - Gamma knife radiosurgery for medically and surgically refractory prolactinomas.
AB  - OBJECTIVE: Experience with gamma knife radiosurgery (GKRS) for prolactinomas is
      limited because of the efficacy of medical and surgical intervention. Patients
      who are refractory to medical and/or surgical therapy may be treated with GKRS.
      We characterize the efficacy of GKRS for medically and surgically refractory
      prolactinomas. METHODS: We reviewed our series of patients with prolactinomas who
      were treated with GKRS after failing medical and surgical intervention who had at
      least 1 year of follow-up. RESULTS: Twenty-three patients were included in
      analysis of endocrine outcomes (median and average follow-up of 55 and 58 mo,
      respectively) and 28 patients were included in analysis of imaging outcomes
      (median and average follow-up of 48 and 52 mo, respectively). Twenty-six percent
      of patients achieved a normal serum prolactin (remission) with an average time of
      24.5 months. Remission was significantly associated with being off of a dopamine
      agonist at the time of GKRS and a tumor volume less than 3.0 cm3 (P < 0.05 for
      both). Long-term image-based volumetric control was achieved in 89% of patients.
      Complications included new pituitary hormone deficiencies in 28% of patients and
      cranial nerve palsy in two patients (7%). CONCLUSION: Clinical remission in 26%
      of treated patients is a modest result. However, because the GKRS treated tumors
      were refractory to other therapies and because complication rates were low, GKRS
      should be part of the armamentarium for treating refractory prolactinomas.
      Patients with tumors smaller than 3.0 cm3 and who are not receiving dopamine
      agonist at the time of treatment will likely benefit most.

PMID- 16883167
TI  - Neurofiberscopic biopsy of tumors of the pineal region and posterior third
      ventricle: indications, technique, complications, and results.
AB  - OBJECTIVE: Evaluation of results of the neurofiberscopic biopsy of tumors of the
      pineal region and posterior third ventricle. METHODS: From 2001 to 2004, 23
      patients (mean age, 30.6 yr) with tumors located in the pineal region or
      posterior third ventricle underwent neurofiberscopic biopsy with simultaneous
      third ventriculostomy. The procedure was indicated for verification of the
      histological diagnosis of the neoplasm, which was planned to be treated by
      radiotherapy and/or chemotherapy without open surgery (eight patients),
      establishment of the pathological diagnosis for further choice of the most
      appropriate treatment strategy (11 patients), differentiation of the recurrent
      neoplasm and radiation necrosis (two patients), and decompression of the large
      tumor-associated cyst (two patients). In six previously shunted patients,
      substitution of the ventriculoperitoneal shunt on the third ventricle stoma was
      performed. RESULTS: There was no postoperative mortality or permanent morbidity.
      In all cases, the obtained tissue sample was sufficient for pathological
      diagnosis. Transient postoperative complications included fever (15 patients),
      nausea and vomiting (three patients), and diplopia (one patient). On the long
      term follow-up, delayed third ventricular stoma failure caused by tumor regrowth
      and scar formation was found in one patient, and dissemination of the malignant
      glioma through the subarachnoid space was found in another patient. CONCLUSION:
      Neurofiberscopic biopsy represents a useful method for sampling of tumors of the
      pineal region and posterior third ventricle, which can be effectively used in
      both previously shunted and shunt-free patients.

PMID- 16883168
TI  - Neuroendoscopic management of symptomatic septum pellucidum cysts.
AB  - OBJECTIVE: Ten rare cases of symptomatic septum pellucidum cysts in patients who
      underwent endoscopic fenestration are described. The approaches and techniques
      used in the management of these cysts and the endoscopic surgical indications are
      discussed. CLINICAL PRESENTATION: In the past 5 years, 10 patients (age range, 3
      60 yr) with symptomatic septum pellucidum cysts underwent neuroendoscopic
      fenestration. The most common symptom was intermittent headache (seven patients)
      accompanied by dizziness, vomiting, and epileptic seizures. Two patients
      presented with epileptic seizures. One patient presented with abnormally
      increased head circumference. Magnetic resonance imaging scans of 10 patients
      showed septum pellucidum cysts, two with hydrocephalus, and two with pituitary
      microadenoma. INTERVENTION: All 10 patients underwent endoscopic fenestration
      with a rigid endoscope via a frontal approach. Eight cases were performed
      freehand. Two cases were assisted by a frameless neuronavigation system.
      Postoperatively, the mass effect of the cysts and the symptoms resolved
      immediately, and computed tomographic or magnetic resonance imaging scans showed
      significant decrease in the cyst size and no recurrence during follow-up.
      Ventricular sizes in the two patients with hydrocephalus were normal. CONCLUSION:
      Neuroendoscopic pellucidotomy could be an effective, safe, and convenient
      therapeutic method for symptomatic septum pellucidum cysts. This approach might
      provide communication between the cyst and the ventricular system, thus avoiding
      shunting or craniotomy. We consider that it is appropriate to use the rigid
      endoscope via the frontal approach. It is helpful to fill the ventricles with
      lactated Ringer's solution and leave an external drain after surgery.

PMID- 16883169
TI  - Critical postcraniotomy cerebrospinal fluid hypovolemia: risk factors and outcome
      analysis.
AB  - OBJECTIVE: Critical cerebrospinal fluid (CSF) hypovolemia may cause acute
      postoperative clinical deterioration in aneurysmal subarachnoid hemorrhage
      patients after craniotomy for microsurgical aneurysm clipping. We sought to
      identify risk factors for critical CSF hypovolemia and determine this syndrome's
      effect on clinical outcome. METHODS: Between April 2001 and June 2004 at Columbia
      University Medical Center, 16 aneurysmal subarachnoid hemorrhage patients were
      diagnosed with postoperative critical CSF hypovolemia, whereas 151 patients who
      underwent craniotomy for clipping were not. The demographics, as well as the
      presenting radiographic and clinical characteristics, of these groups were
      evaluated. In addition, a 2:1 matched case-control comparison of patients with
      and without critical CSF hypovolemia was completed using clinical data, operative
      variables, and outcome data. Outcome analysis was performed with a battery of
      tests designed to assess global outcome, cognitive function, independence, and
      quality of life. RESULTS: There was no difference in clinical grade, Fisher
      score, age, and sex distribution between patients diagnosed with critical CSF
      hypovolemia and the general aneurysmal subarachnoid hemorrhage population at
      Columbia University Medical Center. Subsequent 2:1 matched case-control
      comparison demonstrated a higher incidence of global cerebral edema on admission
      computed tomographic scans (75 versus 31%; P < 0.01) and a significantly longer
      operative time for patients with critical CSF hypovolemia (5 h 18 min versus 4 h
      22 min; P < 0.03). No significant differences were observed between groups in
      outcome assessments at the time of hospital discharge or the 3-month follow-up
      examination. CONCLUSION: Risk factors associated with an increased incidence of
      critical CSF hypovolemia after aneurysm surgery include the presence of global
      cerebral edema on admission head computed tomographic scans and prolonged
      operative time. In such patients, heightened suspicion of CSF hypovolemia is
      crucial because rapid and appropriate management obviates excess morbidity and
      mortality.

PMID- 16883170
TI  - Endovascular treatment for pseudo-occlusion of the internal carotid artery.
AB  - OBJECTIVE: The surgical benefit to pseudo-occlusion of the internal carotid
      artery (ICA) is controversial. Because the benefit of carotid endarterectomy for
      pseudo-occlusion of the ICA remains uncertain, we examined the use of carotid
      stenting as a possible alternative treatment for this condition. METHODS: Twenty
      cases of carotid pseudo-occlusion (17 symptomatic, three asymptomatic) were
      treated with carotid artery stenting. Nineteen patients were treated with various
      embolic protection techniques. Our clinical results, including angiographic
      follow-up data, perioperative complications, and data on the effectiveness of the
      embolic protection methods were studied for ICA pseudo-occlusion. RESULTS: All
      pseudo-occlusions were successfully dilated, and the stenotic ratio was reduced
      from 95 to 6.7% on average. No neurological deterioration was encountered in any
      of the cases, although one patient died of cardiac event 1 day after treatment.
      None of the patients experienced stroke during the mean 24.8 month follow-up
      period, although one patient died from myocardial infarction. Among the 17 cases
      in which follow-up angiography was performed at 6 months after stenting, only one
      patient demonstrated restenosis. This patient was successfully treated with
      repeated percutaneous transluminal angioplasty. The rate of restenosis in our
      series was 5.9%, and the morbidity/mortality rate within 30 days was 5%.
      CONCLUSION: The clinical results of carotid stenting for ICA pseudo-occlusion
      under embolic protection were fairly good from the viewpoints of periprocedural
      neurological morbidity, angiographic follow-up results, and stroke prevention.
      Carotid stenting can be considered an alternative to carotid endarterectomy in
      patients with ICA pseudo-occlusion.

PMID- 16883171
TI  - Dynamic perfusion computed tomography in the diagnosis of cerebral vasospasm.
AB  - OBJECTIVE: The aim of the study was to correlate absolute cerebral blood flow
      (CBF) and mean transient time (MTT) measured by dynamic perfusion computed
      tomographic (PCT) scanning with the clinical course, vasospasm severity, and
      perfusion abnormality in patients with cerebral vasospasm after aneurysmal
      subarachnoid hemorrhage. METHODS: Forty-six patients with vasospasm after
      aneurysmal subarachnoid hemorrhage had 63 PCT images obtained during the course
      of vasospasm. All patients had transcranial Doppler measurements, 28 had an
      angiography study, and 38 had 99mTc single-photon emission computed tomographic
      imaging performed in conjunction with the PCT scan. RESULTS: The average minimal
      regional CBF (rCBF) and maximal regional MTT in patients with delayed ischemic
      deficit were significantly different in comparison with patients without delayed
      ischemic deficit (22.6 +/- 11.2 cm3/100 g/min versus 45.2 +/- 21.3 cm3/100 g/min,
      P < 0.001; 7.3 +/- 2.5 s versus 3.3 +/- 1.7 s, P < 0.05). The average minimal
      rCBF and maximal regional MTT in middle cerebral vascular territories in which
      severe middle cerebral artery vasospasm was measured by transcranial Doppler were
      significantly different in comparison with middle cerebral vascular territories
      in which no vasospasm was measured by transcranial Doppler (29.3 +/- 1.7 cm3/100
      g/min versus 54.1 +/- 25.4 cm3/100 g/min, P < 0.01; 4.5 +/- 2.4 s versus 2.8 +/-
      1.1 P < 0.001). The average minimal rCBF and maximal rMTT in vascular territories
      with estimated severe hypoperfusion on single-photon emission computed
      tomographic imaging were significantly different in comparison with values in
      vascular territories with unimpaired perfusion as estimated by single-photon
      emission computed tomographic imaging (18.9 +/- 6.9 cm3/100 g/min versus 54.2 +/-
      23.4 cm3/100 g/min, P < 0.001, 0.001; 8.1 +/- 1.9 s versus 2.5 +/- 0.39 s, P <
      0.001). CONCLUSION: The present study suggests that, in general, quantitative
      measurements of rCBF and regional MTT by PCT show high concordance rates with the
      clinical course, vasospasm severity, and hemodynamic impairments in patients with
      cerebral vasospasm aneurysmal subarachnoid hemorrhage.

PMID- 16883172
TI  - Intracranial pressure during wakefulness and sleep in 55 adult patients with
      chronic hydrocephalus.
AB  - OBJECTIVE: To record the levels of intracranial pressure (ICP) during wakefulness
      and sleep in hydrocephalic adults and to correlate the ICP levels with symptoms
      and degree of improvement after surgical treatment. METHODS: ICP and patient
      behavior were registered overnight (17-26 h) in 29 patients with noncommunicating
      and 26 with communicating hydrocephalus. Mean ICP was calculated during
      wakefulness (sitting or lying supine) and during sleep. Clinical symptoms and
      changes after surgery were scored on a continuous scale. RESULTS: Mean ICP during
      sleep was 13.4 mmHg (11.1-15.7 mmHg) in noncommunicating hydrocephalus versus
      10.1 mmHg (8.8-11.4 mmHg) in communicating hydrocephalus (P < 0.001). Patients
      with idiopathic communicating hydrocephalus had higher ICP, 11.4 mmHg (9.9-12.9
      mmHg), than patients with secondary communicating hydrocephalus, 8.6 mmHg (6.5
      10.6 mmHg). ICP was higher during sleep than when the patients were awake lying
      supine, 10.9 mmHg (8.7-13.1 mmHg) in noncommunicating versus 6.8 mmHg (5.3-8.3
      mmHg) in communicating hydrocephalus (P < 0.0001). The mean ICP in the sitting
      position was 2.4 mmHg (0.5-4.3 mmHg) in noncommunicating versus 0.5 mmHg (-0.7
      1.8 mmHg) in communicating hydrocephalus. All but one patient with communicating
      hydrocephalus had a normal ICP (< or = 15 mmHg) versus 20 of the 29 patients with
      noncommunicating hydrocephalus. ICP levels showed no correlation with either
      symptoms or improvement after surgery. CONCLUSION: ICP is higher during sleep
      than during periods of awake lying supine (P < 0.001) and is not correlated with
      either symptoms or the rate of improvement after surgery. ICP is normal in most
      adults with hydrocephalus.

PMID- 16883173
TI  - Dual-portal endoscopic release of the transverse ligament in carpal tunnel
      syndrome: results of 411 procedures with special reference to technique,
      efficacy, and complications.
AB  - OBJECTIVE: Endoscopic release of carpal tunnel syndrome is still under debate.
      The main advantages of the technique are considered to be minor postoperative
      pain and a more rapid postoperative recovery. Disadvantages are thought to be the
      impossibility of a direct median nerve neurolysis and a higher surgical
      complication rate, including injury to the median nerve. METHODS: The results of
      411 consecutive endoscopic carpal tunnel procedures performed between March 1995
      and September 2004 are presented. All patients were prospectively followed.
      RESULTS: In the present series, a success rate of 98.05% was observed. There was
      no permanent morbidity and, in particular, there was no injury of the median
      nerve. In four (0.97%) patients, the preoperative symptoms did not improve. In
      two (0.49%) of these patients, an incomplete release of the carpal ligament
      occurred. In another four patients (0.97%), a switch to open surgery was
      required. CONCLUSION: The present data prove that the endoscopic technique is a
      safe and reliable technique for carpal tunnel surgery. The data do not support
      the current discussion of a higher risk of median nerve injury with endoscopic
      carpal tunnel surgery. Thus, for our group, the endoscopic technique represents
      the therapy of choice for the primary idiopathic carpal tunnel syndrome.

PMID- 16883174
TI  - Pathobiology of pituitary adenomas and carcinomas.
AB  - OBJECTIVE: To examine relationships between pituitary tumors and lesion size,
      invasiveness, resectability, deoxyribonucleic acid ploidy, cell cycle profile,
      mitotic activity, and immunoreactivity for MIB-1, proliferating cell nuclear
      antigen (PCNA), p27Kip1, and p53. PATIENTS AND METHODS: One hundred fifty-three
      adenomas of most pathological subtypes, including 20 medically treated and
      prolactin and growth hormone-containing tumors, as well as 10 premetastatic
      tumors and 13 pituitary carcinomas, were studied. RESULTS: Significant (P < 0.05)
      differences were noted between functional versus nonfunctional adenomas (percent
      aneuploidy, percent S phase, p27Kip1 labeling indices [LI], male sex, tumor size,
      and frequency of visual disturbance); Cushing's versus silent adrenocorticotropin
      adenomas (percent hypertetraploidy, p53 LI, tumor size, visual disturbance, and
      resectability); untreated versus medically treated prolactin cell adenomas (MIB-1
      LI, p53 LI, and resectability); untreated versus medically treated growth hormone
      containing adenomas (percent diploidy, percent S phase, MIB-1 LI, p53 LI, and p27
      LI); untreated prolactin cell adenomas versus premetastatic tumors (percent
      hypertetraploidy, PCNA LI, p53 LI, invasiveness, and resectability); untreated
      growth hormone-containing adenomas versus premetastatic tumors (percent diploidy,
      percent S phase, PCNA LI, p53 LI, invasiveness, and resectability); Cushing's
      adenomas versus premetastatic tumors (percent diploidy, percent hypertetraploidy,
      percent S phase, MIB-1 LI, p53 LI, tumor size, invasiveness, visual disturbance,
      and resectability); Nelson's adenomas versus premetastatic tumors (p53 LI, tumor
      size, invasiveness, and resectability); silent adenomas as a whole versus
      nonfunctional adenomas (percent nondiploid, percent S phase, invasiveness, and
      respectability); silent adrenocorticotropin adenomas I and II versus silent
      adenoma Subtype III (invasiveness); silent adrenocorticotropin adenoma Subtypes I
      and II versus premetastatic tumors (MIB-1 LI and invasiveness); silent adenoma
      Subtype III versus premetastatic tumors (PCNA and p53 LI); and premetastatic
      tumors versus metastatic pituitary carcinomas (MIB-1 LI). CONCLUSION: Only trends
      toward differences were noted between Cushing's versus Nelson's adenomas and
      between prolactinomas of reproductive female patients versus those of menopausal
      female patients and male patients. Too few "atypical adenomas" were encountered
      to permit their comparison with premetastatic tumors, but our results suggest
      that most pituitary carcinomas arise by malignant transformation from adenomas.

PMID- 16883175
TI  - Microanatomy of the central myelin-peripheral myelin transition zone of the
      trigeminal nerve.
AB  - OBJECTIVE: The aim of this study was to evaluate the microanatomy of the central
      myelin-peripheral myelin transitional zone (TZ) in trigeminal nerves from
      cadavers. METHODS: One hundred trigeminal nerves from 50 cadaver heads were
      examined. The cisternal portion of the nerve (from the pons to Meckel's cave) was
      measured. Horizontal sections were stained and photographed. The photomicrographs
      were used to measure the extent of central myelin on the medial and lateral
      aspects of the nerve and to classify TZ shapes. RESULTS: The cisternal portions
      of the specimens ranged from 8 to 15 mm long (mean, 12.3 mm; median, 11.9 mm).
      The data from the photomicrographs revealed that the extent of central myelin
      (distance from pons to TZ) on the medial aspect of the nerve (range, 0.1-2.5 mm;
      mean, 1.13 mm; median, 1 mm) was shorter than that on the lateral aspect (range,
      0.17-6.75 mm; mean, 2.47 mm; median, 2.12 mm). CONCLUSION: The data definitively
      prove that the root entry zone (REZ, nerve-pons junction) and TZ of the
      trigeminal nerve are distinct sites and that these terms should never be used
      interchangeably. The measurements showed that the central myelin occupies only
      the initial one-fourth of the trigeminal nerve length. If trigeminal neuralgia is
      caused exclusively by vascular compression of the central myelin, the problem
      vessel would always have to be located in this region. However, it is well known
      that pain from trigeminal neuralgia can resolve after vascular decompression at
      more distal sites. This suggests that the effects of surgical decompression are
      caused by another mechanism.

PMID- 16883176
TI  - Transcranial Doppler grading criteria for basilar artery vasospasm.
AB  - OBJECTIVE: Transcranial Doppler (TCD) criteria for basilar artery (BA) vasospasm
      are poorly defined, and grading criteria for vertebrobasilar vasospasm are
      unavailable. The purpose of the present study was to define TCD grading criteria
      for BA vasospasm on the basis of the absolute flow velocities and the
      intracranial to extracranial flow velocity ratios for the posterior circulation,
      and to improve the sensitivity and specificity of TCD for diagnosis of BA
      vasospasm. METHODS: One hundred twenty-three patients with aneurysmal
      subarachnoid hemorrhage underwent 144 cerebral arteriograms with views of the BA
      during the acute phase of vasospasm (Days 3-14 after hemorrhage). BA diameters
      were measured and compared with diameters obtained from baseline arteriograms.
      Both BA and extracranial vertebral artery flow velocities were measured by TCD
      within 4 hours before the arteriogram. RESULTS: The velocity ratio between the BA
      and the extracranial vertebral arteries (VA) strongly correlated with the degree
      of BA narrowing (r2 = 0.648; P < 0.0001). A ratio higher than 2.0 was associated
      with 73% sensitivity and 80% specificity for BA vasospasm. A ratio higher than
      2.5 with BA velocity greater than 85 cm/s was associated with 86% sensitivity and
      97% specificity for BA narrowing of more than 25%. A BA/VA ratio higher than 3.0
      with BA velocities higher than 85 cm/s was associated with 92% sensitivity and
      97% specificity for BA narrowing of more than 50%. CONCLUSION: The BA/VA ratio
      improves the sensitivity and specificity of TCD detection of BA vasospasm. On the
      basis of the BA/VA ratio and BA mean velocities, we suggest new TCD grading
      criteria for BA vasospasm.

PMID- 16883177
TI  - Low intracranial compliance increases the impact of intracranial volume insults
      to the traumatized brain: a microdialysis study in a traumatic brain injury
      rodent model.
AB  - OBJECTIVE: The vulnerability of the brain is considered to be increased after
      trauma. The present study was undertaken to determine whether intracranial volume
      insults in the posttraumatic period led to increased metabolic disturbances if
      intracranial compliance was decreased. METHODS: A weight drop technique with a
      brain compression of 1.5 mm was used for injury. Intracranial compensatory volume
      was decreased 60 microl by placing rubber film between the dura mater and the
      bone. Intracranial volume insults were induced using the Bolus injection
      technique. Microdialysis was used to measure interstitial lactate, pyruvate,
      hypoxanthine, and glycerol. Fifty-two rats were allocated to trauma and sham
      groups with 0 to 3 layers of rubber film with and without intracranial volume
      insults. RESULTS: In the groups with reduced intracranial volume exposed to
      intracranial volume insults, the time course of metabolic markers showed higher
      increases and slower recovery rates than for the other groups. Reduced
      intracranial volume or intracranial volume insults alone did not cause any
      changes compared with controls. CONCLUSION: These results support the hypothesis
      that decreased intracranial compliance increases the vulnerability of the brain
      for secondary volume insults even with intracranial pressure at low levels
      between the insults. This finding has important clinical implications in that it
      stresses the need to identify patients with low intracranial compliance so that
      their treatment can be optimized.

PMID- 16883178
TI  - Incorporation of bone marrow-derived Flk-1-expressing CD34+ cells in the
      endothelium of tumor vessels in the mouse brain.
AB  - OBJECTIVE: Neoangiogenesis is a prerequisite for the full phenotypic expression
      and growth of a malignant tumor mass. It is believed to be triggered by tissue
      hypoxia and involves proliferation and sprouting of the preexisting vessels and
      the recruitment of endothelial progenitor cells from bone marrow. METHODS: A
      chimeric mouse model was used to examine the contribution of these progenitor
      cells to the neovasculature of brain tumor. T-cell knockout (RAG/KO5.2) mice were
      irradiated lethally, and their bone marrow was repopulated with T-cell depleted
      green fluorescent protein (GFP)-expressing bone marrow cells. RAG/RT-2 glioma
      cells were implanted into the striatum of the animals. Neovascular formation at
      various times of tumor growth was monitored together with the extent of
      incorporation of GFP+ bone marrow-derived cells within the vascular tree, in
      particular, cells carrying the endothelial progenitor markers CD34 and Flk-1.
      RESULTS: The recruitment of GFP+ cells to the growing tumor and their
      incorporation into the vascular network occurred during the period of increasing
      vascular density and preceded the expansion of the tumor. The number of marrow
      derived cells with endothelial morphology and phenotype was small but significant
      (4% of all endothelial cells at Day 12); 54% of all tumor vessels contained at
      least one GFP+ cell. CONCLUSION: Our results suggest that bone marrow cells are
      recruited to newly formed and remodeled tumor vessels. Their recruitment may
      occur in response to signals from a highly proliferating milieu, and their role
      is to support the neovascular complex and to promote tumor growth.

PMID- 16883180
TI  - Francesco Durante: the history of intracranial meningiomas and beyond.
AB  - FRANCESCO DURANTE FROM Letojanni, Sicily, was the first surgeon in the history of
      neurosurgery to successfully remove a cranial base meningioma. Durante was
      Chairman of Clinical Surgery at the Royal University of Rome (now University "La
      Sapienza") for 45 years, participating in the birth of the "Policlinic Umberto
      I," and was one of the most famous surgeons in the country. He was also a Master
      in general surgery, a Senator of the Kingdom of Italy, and a personal friend of
      the King of Italy and the Emperor of Austria-Hungary. His contributions are still
      applicable to medicine today, not only to the neurosurgical community, but also
      other surgical disciplines, because he developed innovative practices in the
      fields of oncology, general surgery, and orthopedics in addition to designing
      special surgical instruments. In commemoration of his legacy, the International
      Francesco Durante Award is bestowed upon world-renowned surgeons.

PMID- 16883179
TI  - A cerebroprotective dose of intravenous citrate/sorbitol-stabilized
      dehydroascorbic acid is correlated with increased cerebral ascorbic acid and
      inhibited lipid peroxidation after murine reperfused stroke.
AB  - OBJECTIVE: Oxidative damage has been implicated in the pathogenesis of cerebral
      ischemia. We previously demonstrated that exogenously supplied dehydroascorbic
      acid (DHA), an oxidized, blood-brain barrier transportable form of the
      antioxidant ascorbic acid (AA), improves outcome after experimental stroke.
      METHODS: To investigate the neuroprotective effect of DHA therapy, we measured
      cerebral AA levels using a novel assay, quantified markers of lipid peroxidation,
      and evaluated infarct volume after reperfused stroke in a murine model. All
      experiments were performed using a new citrate/sorbitol-stabilized DHA
      formulation to improve the stability of the compound. RESULTS: Intraparenchymal
      AA levels declined after cerebral ischemia/reperfusion and were repleted in a
      dose-dependent fashion by postischemic administration of intravenous DHA (P <
      0.01). Repletion of these levels was associated with reductions in cerebral
      malondialdehyde levels (P < 0.05), which were also elevated after reperfused
      stroke. DHA repletion of interstitial AA levels and reduction in cerebral lipid
      peroxidation was associated with dose-dependent reductions in infarct volume (P <
      0.05). CONCLUSION: Together, these results indicate that an intravenous
      cerebroprotective dose of citrate/sorbitol-stabilized DHA is correlated with
      increased brain ascorbate levels and a suppression of excessive oxidative
      metabolism.

PMID- 16883181
TI  - Management of spinal disorders and trauma in Avicenna's Canon of medicine.
AB  - WE STUDY HISTORY in an attempt to achieve a wide perspective of life and reality.
      Spinal disorders, particularly spine traumas and their complications, have been
      one of the most challenging problems throughout the history of medicine and,
      indeed, throughout the history of humanity. The pioneers and founders of
      scientific medicine committed much of their lives to understanding these
      disorders. There is a paucity of historical documentation. From the extraordinary
      efforts of early practitioners, we may glean insight relevant to the more
      effective treatment of such debilitating disorders. Ibn Sina (Avicenna), who
      lived in the medieval period, was one such physician. His principal book of
      medicine, The Canon, played a fundamental role in the practice of medicine in the
      Eastern and Western worlds between the 11th and 17th centuries. In this book,
      published in the 11th century, he provided detailed accounts of spinal disorders
      and strategies for their management. Here, we provide a brief review of
      Avicenna's most significant points concerning spinal diseases and their treatment
      from the chapters of the Canon. Although, there are not basic differences from
      Hippocratic knowledge, this book contains some original contributions.

PMID- 16883182
TI  - Suleymaniye Kulliyesi: a historically important medical, scientific, and cultural
      center.
AB  - SCIENCE HAS MANY Western and Eastern historical roots. All of these contributed
      to the body of academic literature. One of the most important aspects of
      scientific progress is educational institutions, including hospitals, schools,
      and libraries. Some of these institutions may offer an identity for a city, as
      well as contribute to its development. Suleymaniye Kulliyesi is one such
      institution. Suleymaniye Kulliyesi, established in the 16th century, contains
      many centers, including a mosque, surrounded by a hospital, school of medicine,
      central pharmacy, and library. It once served both the Ottoman Empire and the
      Turkish Republic. The school of medicine of this complex was the first school of
      medicine in the Ottoman period that functioned in coordination with the hospital
      and central pharmacy. The library contains many rare books and manuscripts.
      Currently, it is one of the richest centers in the field of oriental studies. We
      conclude that Suleymaniye Kulliyesi, with its health-related elements and
      library, contributed to the development and progress of science and deserves to
      be cited in the literature of the Western world.

PMID- 16883183
TI  - The Portrait of Gertrude Stein at 100.
AB  - ONE HUNDRED YEARS ago, the 24-year-old Pablo Picasso painted the masterpiece
      Portrait of Gertrude Stein. The portrait was a landmark and a turning point for
      both artist and model. The painting, completed in 1906 in Paris, marked a radical
      stylistic change for Picasso and was a transitional work signaling the beginnings
      of Cubism. Gertrude Stein, along with her brothers, was a collector of modern art
      at the turn of the century. Her weekly "salons" in Paris became legendary and
      provided a place for intellectuals of the day--writers, painters, critics, and
      poets--to congregate and exchange ideas. Gertrude Stein's collecting was
      paralleled by her writing of avant-garde prose. Her style was radical and
      influential, and the construction and syntax of her works was a literary analog
      of the Cubist artwork she was collecting in the early 1900s. Gertrude Stein
      became an enduring cultural icon and her portrait stayed with her in France from
      the time of its creation in 1906, through both World Wars, and until her death in
      1946. The portrait remained with her companion, Alice B. Toklas, until its
      bequest to the Metropolitan Museum of Art in New York. Universally recognized as
      one of the classic and pivotal works of Picasso's late Rose period, Portrait of
      Gertrude Stein brilliantly captures the psychological character of one of the
      great American writers and cultural figures of the last century.

PMID- 16883184
TI  - Ulysses and the Sirens by Herbert James Draper (1863-1920).

PMID- 16883187
TI  - Cardiogenic shock--Beyond the large infarction.

PMID- 16883188
TI  - Improving access to intensive care: Is insurance the problem?

PMID- 16883189
TI  - Strengthening community consultation in critical care and emergency research.

PMID- 16883190
TI  - Alone at life's end: Trying to protect the autonomy of patients without
      surrogates or decision-making capacity.

PMID- 16883191
TI  - Making the wrong choice: Consequences for patients with infections due to
      methicillin-resistant Staphylococcus aureus.

PMID- 16883192
TI  - Breathing patterns as integrative weaning predictors: Variations on a theme.

PMID- 16883193
TI  - Evidence that prevention makes cents: Costs of catheter-associated bloodstream
      infections in the intensive care unit.

PMID- 16883194
TI  - Hemofiltration: The case for removal of sepsis mediators from where they do harm.

PMID- 16883195
TI  - Care of the critically ill elderly: Time to move to the next generation of care
      delivery.

PMID- 16883196
TI  - Thrombotic thrombocytopenic purpura: Going with the evidence.

PMID- 16883197
TI  - B-type natriuretic peptide as a marker of heart failure: Not so specific after
      all?

PMID- 16883198
TI  - Percutaneous versus surgical tracheostomy: The continuing saga.

PMID- 16883199
TI  - Estimated versus measured height and weight in the intensive care unit: How do
      ICU clinicians measure up?

PMID- 16883200
TI  - We have the black box recorder--We don't have the key.

PMID- 16883201
TI  - Factor V Leiden and sepsis: Proof positive or phenomenology?

PMID- 16883202
TI  - Natural anticoagulants in sepsis--Too much of a good thing?

PMID- 16883203
TI  - Apnea testing: An effective and safer means.

PMID- 16883204
TI  - Cerebral edema in pediatric diabetic ketoacidosis: Can six patients make a
      difference?

PMID- 16883205
TI  - Should the transbrachial route be used for intra-aortic balloon pumps? Almost
      never!

PMID- 16883207
TI  - The evolving management of traumatic brain injury: Don't shoot the messenger.

PMID- 16883208
TI  - Comparing apples and oranges ...

PMID- 16883209
TI  - Monitoring delirium and sedation.

PMID- 16883213
TI  - Intrathoracic blood volume and global end-diastolic volume should be included
      among indexes used in intensive care for assessment of fluid responsiveness in
      spontaneously breathing patients.

PMID- 16883212
TI  - Oximes in acute organophosphate poisoning.

PMID- 16883216
TI  - [Assessment of clinical course, prognosis and effectiveness of drug and nondrug
      treatment of patients with ischemic heart disease and occlusive coronary artery
      atherosclerosis (data of 5-year prospective follow-up)].
AB  - Data of 5-year prospective follow-up were used for assessment of clinical course,
      prognosis and effectiveness of drug and nondrug treatment of 202 patients with
      ischemic heart disease, occlusive coronary artery atherosclerosis and preserved
      left ventricular function. It was found that 5-year cardiovascular mortality and
      rate of nonfatal myocardial infarction did not differ significantly between
      groups of patients subjected to drug treatment only, transluminal balloon
      angioplasty, and coronary artery bypass grafting.

PMID- 16883217
TI  - [Controlled administration of simvastatin and common therapy of hyperlipidemia in
      patients with ischemic heart disease in outpatient conditions: comparative
      investigation of two strategies (SIGNAL-CONTROL)].

PMID- 16883218
TI  - [Ischemic cardiomyopathy: remote complications and their prognostication after
      isolated myocardial revascularization].
AB  - Aim of investigation was to study rate of remote cardiovascular complications
      after aorto-coronary grafting (ACG) in patients with ischemic cardiomyopathy and
      revelation of informative pre- and early postoperative markers of left
      ventricular (LV) function for determination of prognosis of cardiovascular
      complications and functional state of patients in remote postoperative period.
      Doppler echocardiographical parameters of left ventricular function were assessed
      in pre- and early postoperative period in 107 patients in whom cardiovascular
      events did not recur in late postoperative period (during 1 year) and in 63
      patients who had recurrent cardiovascular events. Influence of a sign (x) on
      probability p(x) of cardiovascular events in postoperative period was estimated
      on the basis of logistic model. Rate of cardiovascular complications during 1
      year after ACG in patients with ischemic cardiomyopathy was 40%. Most significant
      prognostic markers of cardiovascular complications in remote postoperative period
      were LV ejection fraction and deceleration time of early filling before surgery
      and in early postoperative period, as well as LV end systolic diameter in early
      postoperative period (p<0.05).

PMID- 16883219
TI  - [Prestarium in patients with arterial hypertension and ischemic heart disease (or
      risk factors) -- safe achievement of target blood pressure level (the PREMIERA
      study)].

PMID- 16883220
TI  - [Cerebral and myocardial perfusion in patients with arterial hypertension and
      metabolic syndrome after monotherapy with combined drug noliprel].

PMID- 16883221
TI  - [Early use of gemfibrozil in patients with non ST Elevation acute coronary
      syndrome. Changes of markers of inflammation and von Willebrand factor].
AB  - It is not known whether PPAR-alpha agonist gemfibrozil is able to exert rapidly
      its lipid modulating, potential antiinflammatory and antithrombotic effects in
      patients with non-ST elevation acute coronary syndrome (NSTEACS), as some other
      lipid lowering drugs e.g. statins do. METHODS: We randomized 44 patients with
      NSTEACS to open gemfibrozil (n=22, 600 mg b.i.d for 90 days) or no gemfibrozil
      (controls, n=22) within 24 hours after pain onset. Semiquantitative C-reactive
      protein (CRP) latex test was used at baseline for exclusion of patients with
      overt inflammation. All patients received dalteparin or enoxaparin for >48 hours
      and oral aspirin (125 mg/day) and were treated noninvasively. Lipids, high
      sensitive CRP, soluble CD40 ligand (CD40L) and von Willebrand factor (vWF)
      activity were assessed on days 1 (baseline), 4, 7, 14, 30 and (except CD40L) 90.
      RESULTS: Gemfibrozil use was associated with significant lowering of
      triglycerides by day 30, however it did not prevent acute significant decline of
      high density lipoprotein cholesterol (HDL-C), which was similar in both groups.
      CD40L level significantly increased while CRP levels decreased by day 30 in both
      groups. Moreover, selection of a subgroup with baseline HDL-C <1.0 mmol/l did not
      reveal any difference in changes of CRP or CD40L between gemfibrosil treated and
      control patients. vWF activity did not change in controls and significantly
      increased in gemfibrozil group by days 7, 14, but from lower baseline level.
      CONCLUSION: In patients with NSTEACS early administration of gemfibrozil was not
      associated with positive changes of CRP and CD40L levels or vWF activity compared
      with control group.

PMID- 16883222
TI  - [Possible role of hyperinsulinemia in pathogenesis of acute and chronic cardiac
      failure in patients with ischemic heart disease (data of clinical studies)].
AB  - Changes of blood insulin content were studied in patients with ischemic heart
      disease with various functional classes of acute and chronic heart failure and at
      different disease stages. It was established that latent hyperinsulinemia which
      became evident at induced myocardial ischemia was present on all stages of
      development of ischemic heart disease. In acute heart failure due to developed
      myocardial infarction hyperinsulinemia manifested in 58.3% of patients. Amount of
      insulin in blood increased almost 3 times. During progression of chronic heart
      failure insulin content significantly decreased, probably because of exhaustion
      of insulin producing function and development of its relative or absolute
      deficit. At terminal stage of congestive heart failure insulin level was < or = 1
      microU/ml. The authors believe that severity of clinical signs of acute and
      chronic heart failure are determined by sensitivity of myocardium to insulin,
      content of insulin in blood, and also depends on compensatory possibilities of
      insulin producing function at each stage of development of the disease.

PMID- 16883223
TI  - [Preclinical assessment of disturbances of vascular and vegetative reactivity of
      peripheral blood circulation in young men (students) with risk factors of
      atherosclerosis].
AB  - Hemodynamics of forearm and neurovegetative status were studied in 142 clinically
      healthy male students with risk factors of atherosclerosis and in 54 male
      students without risk factors of atherosclerosis at rest and during test with
      reactive hyperemia. Rheovasography of forearm, cardiointervalography, Doppler
      examination of brachial artery, and test with reactive hyperemia were undertaken
      in all subjects. The results testify to the fact that endothelial dysfunction
      leads to spastic state of regional hemodynamics and hyperactivity of sympathetic
      nervous system at rest as well as during reactive hyperemia which has a "delayed"
      character.

PMID- 16883224
TI  - [Adipose tissue stromal cells -- multipotent cells with therapeutic potential for
      stimulation of angiogenesis in tissue ischemia].
AB  - Results of studies of properties of adipose tissue stromal cells are summarized
      in this review. It contains data on separation and cultivation of these cells as
      well as description of their antigenic characteristics, ability to differentiate
      into cells of mesenchymal and nonmesenchymal origin, angiogenic potential, and
      potential for transfection and transfer of therapeutic genes. Analysis of
      perspectives of clinical use of adipose tissue stromal cells in therapy of
      cardiovascular and other diseases is also presented.

PMID- 16883225
TI  - [Factors affecting development of sudden death and risk stratification of
      patients after myocardial infarction].

PMID- 16883226
TI  - [Effect of selective destruction of epicardial nervous plexuses on the function
      of atrio-ventricular node].

PMID- 16883227
TI  - [Pulmonary hypertension and right ventricular failure. Part V. Therapy in the
      patients with chronic obstructive pulmonary disease].
AB  - In a series of articles the authors discuss literature data concerning
      epidemiology of pulmonary hypertension, its modern classification; peculiarities
      of its pathogenesis and treatment in various diseases and conditions. In the
      fifth lecture they present literature data on nondrug interventions and drug
      therapy of patients with chronic obstructive pulmonary disease (COPD),
      complicated with development of chronic cor pulmonale. Contemporary views of the
      role of oxygen therapy and bronchodilators of various type in treatment of COPD
      are discussed in detail. Beneficial effect of dihydropyridine calcium antagonists
      on pulmonary circulation in patients with COPD, possibilities and limitations of
      their long term use in treatment of pulmonary arterial hypertension including
      that in patients with COPD are considered. The authors also consider in detail
      beneficial and harmful properties of drugs, which may be used in treatment of
      patients with COPD, in particular of digoxin, diuretics, spironolactone,
      angiotensin converting enzyme inhibitors. Discussion of indications to phlebotomy
      in patients with COPD and chronic cor pulmonale is presented as well.

PMID- 16883228
TI  - [Value of T-wave alternation for diagnostics of viable arrhythmias].

PMID- 16883230
TI  - [Diagnosis and treatment of complicated postnecrotic cysts of pancreas].
AB  - Experience of complex treatment of 137 patients with complicated postnecrotic
      pancreatic cysts (PPC) is analyzed. Indications to different surgical methods are
      formulated differentially depending on complications of cysts, localization,
      sizes, "maturity" of cyst walls, communication with main pancreatic duct.
      Treatment of festered PPC should be started with minimally-invasive methods; at
      negative result the omentobursocystostomy with staged endoscopic sanations should
      be done that permits to decrease the number of postoperative complications and to
      reduce lethality from 14.3 to 4.5%. Resection of pancreas along with cyst is the
      operation of choice at pancreatic cysts complicated with bleeding; lethality has
      been reduced from 28.6 to 5.6%. Perforation of cysts into abdominal cavity is the
      indication to omentobursocystostomy with staged sanations of omental bursa,
      perforation into pleural cavity -- to distal resection of pancreas.

PMID- 16883229
TI  - [Significance of nitrates in contemporary pharmacotherapy of cardiovascular
      diseases].
AB  - Results of the use of nitrates in various forms of cardiovascular pathology are
      presented and problems related to correctness of application of preparations of
      this group, development of tolerance to them are considered. Results of their use
      in extracardiac pathology are also outlined.

PMID- 16883231
TI  - [Primary diagnosis of infected pancreonecrosis].
AB  - Three hundred and fourteen patients were analyzed including 47 with
      pancreatogenic infiltration, 58 with pancreatogenic abscess, and 209 patients
      with pancreatogenic phlegmon. Clinical and special examinations were used for
      diagnosis. Clinical examination permits to suspect of the one or other form of
      infected pancreanecrosis. Results of clinical and biochemical blood analyses
      don't differ significantly. Data of USE and CT permit to precise the clinical
      form of the disease. The most changes have been revealed in the patients with
      pancreatogenic phlegmon.

PMID- 16883232
TI  - [The effect of organ dysfunction on the outcomes of acute destructive
      pancreatitis].
AB  - The relationships between outcomes of severe acute pancreatitis (SAP) and organ
      dysfunction in 72 patients were studied. A total of 39 (54.2%) patients had organ
      dysfunction, 20 (27.8%) patients -- multiple organ dysfunction (MOD), 19 (26.4%)
      patients -- dysfunction of single organ or system. Died patients had higher
      incidence of MOD compared with those who alive (88.2 vs 9.1%, p<0.01). In
      multiple logistic regression analysis the main predicting factors of death were
      pulmonary failure and neurological dysfunction. Pulmonary failure was the most
      common organ dysfunction among both single organ dysfunction (57.9%) and MOD
      (95.0%), with a total morbidity of 41.7%. Mortality rate was lower at isolated
      pulmonary dysfunction, and was higher at MOD (18.2 vs 78.9%, p<0,01). Irregular
      specialized intensive treatment protocol led to groundless surgical interventions
      at 10 from 46 patients with sterile pancreonecrosis. Organ dysfunction makes
      worse the prognosis in patients with SAP. Choice of the optimal treatment
      strategy at SAP with MOD is determinative.

PMID- 16883233
TI  - [Clinical finding and treatment of festered hepatic echinococcosis].
AB  - Results of treatment of 72 patients with festered hepatic echinococcosis were
      analyzed. Ultrasonic examination was the main method of examination. Method of
      residual cavity liquidation was determined by localization of cyst. Original
      method of liquidation of residual cavity using omentum and oxygen insufflations
      has been successfully applied in 21 patients. Open methods of residual cavity
      liquidation are often accompanied by complications (bile-purulent fistulas,
      residual purulent cavities, long period of treatment).

PMID- 16883234
TI  - [Clinical and laboratory symptoms of space-occupying hepatic lesions and their
      prognostic value].
AB  - Rational complex diagnostic approach has a critical importance in diagnosis of
      space-occupying hepatic lesions. Results of clinical and special examinations
      permit to assess the state of hemostasis and functional reserve of liver, to
      predict the surgical risk and correct treatment tactics.

PMID- 16883235
TI  - [Transplantation of kidney with multiple arteries].
AB  - One hundred and nine kidney transplantations have been performed. All the
      patients have been divided into 2 groups: 1st group consisted of 91 patients
      whose transplant had 1 artery, 2nd group -- 18 patients whose transplant had 2 to
      5 arteries. In 2.5 years after transplantation the function of transplant and
      degree of arterial hypertension were identical in both groups. It is concluded
      that the short- and long-term results of transplantation of kidneys with multiple
      arteries don't differ from ones with single artery.

PMID- 16883236
TI  - [Acute inflammation of greater omentum].
AB  - Results of treatment of 9 patients (3 male, 6 female) with acute omentitis are
      analyzed. Omentitis was primary in 8 patients, and secondary -- in 1 patient.
      Right-sided abdominal localization of pains was the cause of incorrect entrance
      diagnosis (acute appendicitis and acute cholecystitis). All the patients were
      operated, the resection of affected parts of great omentum was performed; in 3
      cases it was supplemented with appendectomy. Problems of pre-operative diagnosis
      of acute omentitis and the choice of optimal variant of surgery are discussed.

PMID- 16883237
TI  - [Aorto-femoral bypass through mini-laparotomy compared with traditional surgery].
AB  - Results of 115 aorto-femoral bypasses through mini-laparotomy (ML-group) are
      compared with the results of 117 similar operations through standard laparotomy
      (SL-group). The patients of both group were similar by main characteristics, but
      the concomitant diseases (coronary heart disease, cerebrovascular disorders,
      chronic obstructive pulmonary diseases) were seen more often in ML-group. It is
      demonstrated that there were no significance differences between two groups in
      number and structure of postoperative complications. Less surgical trauma, short
      rehabilitation period, small risk of postoperative complications and lethality
      are the advantages of mini-laparotomic surgery.

PMID- 16883238
TI  - [Immunological disorders and correction of them in surgical patients with
      atherosclerosis obliterance].
AB  - Atherosclerosis obliterance and critical lower limb ischemia lead to
      immunodeficiency and disbalance of T- and B- components of immune system.
      Surgical treatment doesn't eliminate but in a number of cases aggravates immune
      disorders. Immunocorrection stimulates anti-infectious protection. Indications to
      different variants of immunocorrection are formulated.

PMID- 16883239
TI  - [Deep vein thrombosis as the manifestation of congenital anomaly of inferior vena
      cava].
AB  - Results of examination of 5 male patients aged 20 to 43 years with congenital
      anomaly of inferior vena cava are analyzed. Complex special examination (CT, MRI,
      duplex scanning, pelvic phlebography, retrograde cavagraphy) was used for correct
      diagnosis. Primary treatment of agenesis of inferior vena cava should consist of
      elastic compression and phlebotonics; in cases of deep vein thrombosis
      anticoagulants must be used.

PMID- 16883240
TI  - [Upper-thoracic sympathectomy in the treatment of upper limb ischemia at distal
      form of arterial lesion].
AB  - Efficacy of upper-thoracic sympathectomies performed in 61 patients with chronic
      upper limb ischemia is analyzed. Thoracotomy was used in 20 cases,
      videothoracoscopic approach -- in 56 (including 15 cases of two-sided
      procedures). Efficacy was evaluated with clinical examination, rheovasography,
      laser Doppler-flowmetry, percutaneous detection of tissue oxygen tension.
      Advantages of videothoracoscopy compared with thoracotomy are demonstrated.

PMID- 16883242
TI  - [Criteria of diagnosis of small pelvis varicose veins in women at age-specific
      and biological periods of life].
AB  - Phlebography, ultrasonic, and Doppler examinations of pelvic venous system in
      women at age-specific and biological periods of life were used for diagnosis of
      varicose disease. Increase of the diameter of the main venous collectors and
      decrease of systolic velocity of venous blood flow into uterine veins are the
      main diagnostic criteria.

PMID- 16883241
TI  - [Radiothermometry in diagnosis of thyroid diseases].
AB  - Primary experience (177 patients) of diagnosis of thyroid gland diseases with
      radiothermography using microwave radiothermometer RTM-01-RES is analyzed. In
      unaffected thyroid gland there were no temperature differences between symmetric
      points of right and left lobe. Cancer of thyroid gland and toxic adenoma are
      characterized by higher internal temperature. High sensitivity of method and its
      simplicity are the reasons for use of radiothermography as screening method.

PMID- 16883243
TI  - [Major injury of ileum and great mesenteric vessels at closed abdominal trauma].

PMID- 16883244
TI  - [Multiple combined echinococcosis].

PMID- 16883245
TI  - [Early cancer of stomach].
AB  - Results of surgical treatment of 170 patients with early cancer of the stomach
      are analyzed. There were 113 patients with tumor invasion within the bounds of
      the mucous membrane (m -- 113), the others had invasion within the bounds of the
      submucous membrane (sm -- 57 patients). Impressed and ulcered macroscopic types
      of early cancer (IIc + III) were diagnosed most often: 57% m+sm (97 of 170),
      58.4% m+sm (97 of 170), 54.4% sm (31 of 57), respectively. Poorly differentiated
      tumors prevailed over moderate- and well-differentiated tumors - 68.8% (117 of
      170) and 31.2 (53 of 170) patients, respectively. Subtotal distal resection of
      the stomach has been performed in 118 (69,4%) patients, subtotal proximal
      resection -- in 13 (7.7%), gastrectomy -- in 22 (12.9%), resection of 2/3 stomach
      -- in 14 (8.2%), resection of the cardia - in 3 (1,8%). Lymphadenectomy has been
      performed in 156 patients including 1 (0.6%) patient with D0-lymphadenectomy, 88
      (56.4%) - D1, 62 (39.7%) -- D2, and 5 (3.2%) -- D3. Metastases to the regional
      lymph nodes have been revealed in 8 (5%) cases -- 2 m and 6 sm. Extended
      lymphodissections (D2 and D3) have improved significantly long-term results. Five
      year survival among the patients who had undergone extended operations with D2
      and D3 lymphadenectomies was higher compared with patients after limited and
      standard operations (D0 and D1) -- 96.0+/-2.5 and 87.0+/-3.5%, respectively.

PMID- 16883246
TI  - [Bilroth-I subtotal resection and its efficacy in the treatment of distal gastric
      cancer].
AB  - The experience with 260 Bilrot-I resections for cancer of a distal part of the
      stomach is analyzed. Postoperative lethality was 2.69%, rate of dumping-syndrome 
      - 12.3%. Among 215 followed-up patients treated surgically 5- and 10-year
      survival was 65.1 and 24.7%, respectively. Original surgical methods for
      improvement of immediate and long-term functional results have been developed and
      applied in clinical practice.

PMID- 16883247
TI  - [Fistulography in destructive pancreatitis in postoperative period].
AB  - Results of different x-ray methods applied in 151 patients early after operations
      for destructive pancreatitis were analyzed. The technique of fistulography is
      described. Plain roentgenography of the chest demonstrated changes in 77.4%
      cases, most often occurred disk-shaped atelectases and pleural effusion.
      Examination of the abdominal cavity revealed functional disorders in 69.8% cases,
      direct symptoms of purulent process -- in 52.9%, radiographic signs of aseptic
      sequestration -- in 47.1% patients. X-ray signs of purulent process in the
      retroperitoneal fat and aseptic sequestration of the infiltrate or fat are
      outlined. The value of fistulography for localization and determination of the
      shape of drained cavities, position of the drainage tubes in the cavity,
      condition of the adjacent tissue, progression of purulent process, adequacy of
      drain of the purulent cavities is shown. Based on the results of complex x-ray
      examination with ultrasound investigation and CT data, the indications to
      repeated procedure (surgery or additional drainage) were formulated in 82 (54.3%)
      of 151 patients.

PMID- 16883248
TI  - [Treatment policy for postoperative complications in patients with hepatic
      echinococcosis and bile duct affection].
AB  - Results of surgical treatment of 277 patients with hepatic echinococcosis and
      bile duct affection demonstrated that the rate of specific postoperative
      complications depends on duration of the disease, location and size of the
      parasitic cyst, changes in the cyst (suppuration, calcification), and also on the
      level of the lesion in the bile ducts. They were seen in the lesion of the
      segmental ducts 1.5 times less (18%) often than in the lesion of the hepatic
      ducts (25.7%). Early diagnosis, adequate surgical treatment, characteristics of
      pathological alterations in the cyst and bile ducts influence treatment outcomes.
      Postoperative complications arose in 25.9% cases with lethality 1.4%. These
      complications were diagnosed 6 times less often after elimination of the residual
      cavity, suturing of bile fistulas or other methods (resection, pericyctectomy)
      application than after drainage of the residual cavity.

PMID- 16883249
TI  - [Optimization of prognosis and surgical prophylaxis of bleedings from esophageal
      varicose veins].
AB  - New methods of prediction of bleeding from the esophageal varicose veins improve
      treatment outcomes. These methods consist of endoscopic assessment of varicose
      vein and mucous membrane with determination of thickness of the vein wall and
      mucosa, and also assessment of reflux-esophagitis with endoscopic
      ultrasonography. Original operation of azigoportal disconnection was performed in
      13 patients followed-up after surgery from 1 to 4 years. The results obtained
      demonstrate high efficacy of this surgery for prophylaxis of repeated bleedings
      from esophageal varicose veins.

PMID- 16883250
TI  - [A mini-approach to the abdominal aorta].
AB  - Results of experimental development of mini-approaches to the abdominal aorta for
      bypass surgeries are analyzed. Based on 40 experimental aorto-femoral bypasses
      via transabdominal and extraperitoneal mini-approaches, the main parameters of
      these parameters were compared. It is demonstrated that transabdominal approach
      guarantees adequate exposition of all infrarenal part of aorta, extraperitoneal
      approach -- only a terminal part of the aorta below inferior mesenteric artery.
      The better quality of transabdominal approach according to all Sozon-Yaroshevich
      criteria was also demonstrated.

PMID- 16883251
TI  - [Laser energy in abdominal surgery].
AB  - The results of 210 operations on the gastrointestinal tract with application of
      YAG-Nd laser have been analyzed. The role of laser in the improvement of surgical
      outcomes is demonstrated.

PMID- 16883252
TI  - [Videoendosurgical diagnosis and treatment of abdominal injuries in combined
      trauma].
AB  - Experience with videolaparoscopy in 1332 patients with combined abdominal trauma
      is analyzed. The original method of diagnosis of traumatic abdominal multitraumas
      in shock patients was proposed and patented. Diagnostic and treatment algorithm
      for hemoperitoneum in patients with abdominal multitrauma based on USE or CT data
      on liquid in the abdominal cavity has been developed. Videolaparoscopy helped to
      avoid open surgery in 73.3% patients with dominating abdominal trauma.

PMID- 16883253
TI  - [Surgical policy in reconstructive surgery on the colon].
AB  - Thirty-year experience with 1685 reconstructive operations on the colon is
      analyzed. Novel surgical policy has increased the rate of primary-reconstructive
      operations for the last 5 years from 78.8 to 87.9%, decreased the number of
      postoperative complications from 33 to 21.8%, intestinal anastomosis-dependent
      complications -- from 22.6 to 8.4%, postoperative lethality -- from 6.9 to 2.4%,
      raised the rate of good functional results from 64 to 88.2%.

PMID- 16883254
TI  - [Long-term results of surgical treatment of commissural intestinal obstruction].
AB  - Long-term results of operations for acute commissural intestinal obstruction
      (ACIO) were studied in 128 patients 2 to 10 years after surgery. Only patients
      with uncomplicated forms of ACIO (without intestinal necrosis and generalized
      peritonitis) have been included into the analysis. The results of the treatment
      were assessed both in the group and individually after 87 operations of total
      adheolysis and 39 cases of partial comissurotomies. Clinical symptoms of
      abdominal commissures after elimination of ACIO were seen in 44.2% patients,
      including recurrence of ileus in 20.3% patients. Interintestinal commissures and
      conglomerations were the causes of ACIO in 44.5% cases that should be taken into
      account at adheolysis made laparoscopically. It is demonstrated that long-term
      results of ACIO treatment depend on surgical trauma and associated recurrence of
      adhesive process.

PMID- 16883255
TI  - [Systems of objective assessment of the condition of patients with
      pancreonecrosis].

PMID- 16883256
TI  - [Reconstruction of colon transplants after retrosternal esophagoplasty].

PMID- 16883257
TI  - [Gastric torsion].

PMID- 16883258
TI  - [Laparoscopic cholecystectomy in a patient with visceral inversion].

PMID- 16883259
TI  - [Hormonal regulation of lipoprotein metabolism: the role in pathogenesis of
      coronary heart disease].
AB  - The character and role of hormonal dysregulation of lipoprotein metabolism during
      postprandial hyperlipemia were studied in patients with coronary heart disease
      (CHD) and hyperthyroidism as compared with healthy subjects. Pronounced
      hypertriglyceridemia alongside with the decreased high density lipoprotein
      cholesterol (HDL C) after standard fat load were associated with increased level
      of insulin and decreased level of cortisol. Moreover, in CHD patients fasting
      hyperinsulinemia becoming even stronger postprandially resulted in prevalence of
      antilipolytic action of insulin over lipid-mobilizing effect of cortisol; and an
      extended postprandial hypertriglyceridemia took place. Patients with
      hyperthyroidism and low cholesterol level both in atherogenic LDL and
      antiatherogenic HDL, demonstrated decreased level of apo AI (as in CHD patients)
      and apo B (three times lower than in CHD patients). Very low ratio of apo B/AI in
      patients with hyperthyroidism both in fasting and postprandial state was a clear
      indication of their lipoprotein profile antiatherogeneity. Thus, in patients with
      hyperthyroidism despite of low HDL C and apo AI levels, antiatherogenic
      properties of lipoprotein profile are probably determined by very low apo B/AI
      ratio induced by thyroid hormones, and might be explained by the influence of
      thyroid hormones on the expression of genes coding these apoproteins.

PMID- 16883260
TI  - [Clinical experience of the use of autologous mononuclear bone marrow cells in
      patients with ischemic heart disease and dilated cardiomyopathy].
AB  - Between March 2003 and February 2005 cell therapy with mononuclear bone marrow
      cells (MBMC) was used in 38 and 4 patients with ischemic heart disease and
      dilated cardiomyopathy, respectively. Intracardiac administration of MBMC (87+/
      12 millions) was carried out during coronary artery bypass surgery and/or left
      ventricular aneurysm resection (n=25) or in cardiac catheterization laboratory
      (n=17). For verification of cells fixation they were labeled with "Ceretec" 99mTc
      HMPAO. Accumulation of labeled cells after 24 hours was 1.6+/-0.001%. After 6
      months parameters of intracardiac hemodynamics and transitory myocardial
      perfusion defects improved significantly in all patients with ischemic heart
      disease.

PMID- 16883261
TI  - [Value of various criteria of assessment of a test in stress echocardiography in
      diagnosis of ischemic heart disease].
AB  - Aim of investigation was to study significance of electrocardiographical and
      echocardiographical criteria of development of angina attack, and their
      combination in assessment of results of stress echocardiographical tests (stress
      echo) with various stress-agents. Stress echocardiography, coronary angiography
      and left ventriculography were carried out in 928 patients (805 men and 123
      women) aged 31 - 72 years with suspected ischemic heart disease (IHD). Attack of
      angina (AA) was registered in 324 cases, 1.5 mm ST-segment depression (Scapital
      TE, Cyrillic) -- in 448 tests, disturbances of local myocardial contractility
      (DLC) at piece exercise -- in 625 patients. Coronaro-ventriculography did not
      reveal hemodynamically significant coronary artery lesions in 235 patients.
      Accuracy, sensitivity, and specificity of assessment of stress-echo result were
      for criterion "ST" 62.1, 56.9, 77.4%, respectively, for criterion "AA" - 50.0,
      40.7, 87.0%, respectively, for criterion DLC - 90.7%, 88.9%, 96.2%, respectively,
      for combinations of criteria "ST+DLC" - 46.1, 30.6, 91.9%, "ST+AA" -- 66.7, 56.1,
      97.8, respectively, for "DLC+AA" -- 54.9, 40.5, 97.4%, respectively.
      Echocardiographic criterion DLC appears to be determinant in assessment of
      results of stress-echo tests.

PMID- 16883262
TI  - [Temporary cardiac pacing in patients with acute myocardial infarction in the
      conditions of air medical service].
AB  - Temporary electrical cardiac pacing in the conditions of air medical service was
      used in 183 patients with myocardial infarction complicated with life threatening
      disturbances of cardiac rhythm and conduction. Immediate results of treatment,
      complications, and causes of lethal outcomes are presented. Two groups of
      patients were distinguished: in which traditional and improved by authors methods
      of temporary electrical pacing were employed. It was established that the use in
      urgent situations of improved techniques of control of endocardial electrode
      position, transesophageal, cutaneous, and atrial dependent endocardial
      ventricular electrical pacing allowed to decrease number of complications 2.6
      times, and to lower mortality in acute period of myocardial infarction by 12.8%.

PMID- 16883263
TI  - [Effectiveness and safety of clopidogrel bisulfate in complex therapy of patients
      with acute coronary syndrome with ST segment elevation].
AB  - Efficacy of clopidogrel in acute myocardial infarction (AMI) was studied only in
      two trials. However efficacy and safety of loading dose of this drug and its long
      term effectiveness were not studied in these trials. AIM: To assess effects of
      clopidogrel loading dose and long term therapy in addition to standard treatment
      on death, re-infarction, recurrence of angina and bleedings rate in patients with
      ST segment elevation acute coronary syndrome. METHODS: Patients (n=107) with AMI
      who met the criteria for thrombolytic therapy (TLT) were assigned randomly into
      either clopidogrel group A (n=51) or conventional therapy group B (n=56). Group A
      received loading dose of clopidogrel (300 mg) in addition to conventional therapy
      (TLT, aspirin, statin, ACE inhibitor and beta-blocker). Group B received only
      conventional therapy. The follow-up was 6 months after inclusion during which
      patients in group A continued to receive clopidogrel (75 mg/day after Day 2 of
      the study). Primary endpoint included death, re-infarction, recurrence of angina
      and bleedings. In addition, changes of ST segment after TLT and local
      contractility were assessed. RESULTS: During 30 days of follow-up rates of
      primary endpoint were 2.0 and 41.1% in groups A and B, respectively (p=0.003).
      Subgroup analyses showed that this difference depended on the rate of angina
      recurrence (2.4 and 36.1% in groups A and B, respectively, p=0.002). These
      differences were maintained during all follow-up period. Odds ratios for
      clopidogrel were 0.235 for primary endpoint (95% CI 0.104-0.528, p=0.0003), 0.078
      for angina recurrence (95% CI 0.022-0.279, p=0,0001). No significant differences
      were obtained for mortality, re-infarction and bleeding rate. TLT in group A was
      more effective. ST depression 90 min after TLT was 86.23+/-4.38 and 61.00+/-6.97%
      (p=0.010), reperfusion arrhythmia rate - 72.6+/-3.27 and 33.9+/-2.78% (p=0.005)
      in groups A and B, respectively. CONCLUSION: The use of clopidogrel in addition
      to standard therapy for AMI is safe and effective. Long-term clopidogrel
      treatment decreases angina recurrence rate.

PMID- 16883264
TI  - [Effects of long term therapy with angiotensin converting enzyme inhibitor
      quinapril, antagonist of receptors to angiotensin II valsartan, and combination
      of quinapril and valsartan in patients with moderate chronic heart failure. Main
      results of the SADKO-CHF study].
AB  - AIM: To compare effects of therapy with angiotensin converting enzyme inhibitor
      quinapril (Q), angiotensin II receptor antagonist valsartan (V), and their
      combination in patients with stable moderate chronic heart failure (CHF).
      MATERIAL AND METHODS: Patients (n=80) with NYHA class II-III CHF due to ischemic
      heart disease, dilated cardiomyopathy or decompensated hypertensive heart and
      ejection fraction <40% were randomized into 3 groups. Patients of group Q, V and
      Q+V received Q (average dose 13 mg/day, n=28), V (121 mg/day, n=26), and
      combination of Q and V (12 and 78 mg/day, n=26), respectively. Methods included
      assessment of clinical state and quality of life, echocardiography, 6 min walk
      test, Holter ECG monitoring with measurements of parameters of heart rate
      variability (HRV), and determination of neurohormones in peripheral blood.
      Examinations and measurements were made at baseline, in 3 and 6 months. RESULTS
      AND CONCLUSIONS: Six months therapy with Q, V and their combination resulted in
      improvement of clinical and functional state of patients. More pronounced
      augmentation of exercise tolerance and lowering of CHF functional class were
      observed in group Q. Combined use of Q and V had no significant advantages over
      monotherapy with Q and V when effect on parameters of left ventricular remodeling
      were concerned. Therapy with Q was associated with "escape" of blockade of
      aldosterone synthesis and "reactivation" of angiotensin II formation after 6
      months. The use of V and combination of V+Q allowed to achieve more stable but
      incomplete control of aldosterone activity. The use of Q appears to be the
      preferential regimen to influence activity of sympathoadrenal system and
      parameters of 24 hour HRV compared with V and Q+V. Long term therapy with V does
      not improve main parameters of 24 hour HRV.

PMID- 16883266
TI  - [C-reactive protein level and rate of detection of autoantibodies to beta(1)
      adrenoreceptors in patients with supraventricular tachyarrhythmias].
AB  - In order to assess concentration of C-reactive protein (CRP) and prevalence of
      autoantibodies against beta(1)-adrenoreceptors (abeta(1)-AR) in patients with
      cardiac supraventricular arrhythmias we studied 53 patients with arrhythmias and
      20 healthy control subjects. Patients with idiopathic arrhythmias (atrial
      fibrillation or flutter and atrial tachycardia, n=35) comprised group I. Group II
      was formed of 15 patients with supraventricular arrhythmias and dilated
      cardiomyopathy (DCM) or chronic myocarditis. Patients of group III (n=23) had
      supraventricular arrhythmias and arterial hypertension (AH). CRP concentration
      was determined by recently developed well standardized high sensitivity method.
      abeta(1)-AR were detected in blood serum by direct immunoassay. Synthetic
      fragment containing 26 amino acids of abeta(1)-AR second loop was used as
      antigen. Patients with supraventricular arrhythmias and DCM or chronic
      myocarditis had higher median CRP (8.0 mg/1) than patients with idiopathic
      arrhythmias (0.78 mg/l), with supraventricular arrhythmias and AH (1.57 mg/l), or
      control group (0.6 mg/l). Groups I, II and III showed similar prevalence of ab1
      AR (51.4, 40.0, 52.2%, respectively), that was significantly higher than in
      control subjects (10%) (p<0.005). These results provide evidence of the possible
      presence of autoimmune and/or inflammatory processes that may be involved in the
      genesis of supraventricular arrhythmias.

PMID- 16883265
TI  - [Quadropril (spirapril) in the treatment of isolated systolic hypertension in
      patients with type 2 diabetes mellitus].

PMID- 16883267
TI  - [Comparative study of the antiarrhythmic activity of magnesium aspartate L-, D-
      and DL-aspartate stereoisomers].
AB  - It seems an established fact that magnesium (Mg) aspartate is effective in
      prophylaxis and adjuvant therapy of cardiac arrhythmia (e.g. prevention of toxic
      symptoms during therapy with digoxin). There are claims that L-aspartate salts
      are better delivery forms for cations such as Mg than D-aspartate salts, and Mg L
      aspartate can be more beneficial in the treatment of several forms of primary Mg
      deficiency than Mg DL- and D-aspartate. Therefore, the purposes of the present
      work were to compare of antiarrhythmic action of Mg L-, D- and DL-aspartate
      stereoisomers using CaCl(2)- and aconitine-induced arrhythmia models in rats. It
      was found that intravenously administered Mg L-aspartate exhibited higher
      activity compared to Mg D- and DL-aspartate in calcium chloride and aconitine
      induced arrhythmias. In rats with arrhythmias induced by calcium chloride Mg L
      aspartate compared with Mg D-aspartate and Mg DL-aspartate produced greater
      decrease of incidence of arrhythmias, increase of time first arrhythmia onset,
      decrease of percentage of rats that died and increase of duration of life after
      onset of first arrhythmia. In rats with aconitine-induced arrhythmia Mg L
      aspartate surpassed Mg D-aspartate and Mg DL-aspartate in parameters of acute
      toxicity (LD(50)), effective dose (ED(50)) and antiarrhythmic (therapeutic) ratio
      (LD(50)/ED(50)).

PMID- 16883268
TI  - [Innervation of adrenal glands in some types of cardiovascular pathology].
AB  - We examined adrenal glands obtained at early autopsy of 56 men aged 21-70 years.
      According to the age five groups of cases were distinguished. The study was
      performed with the use of methods of silver impregnation of nerve plexuses and
      planimetric pointcounting. Density of nerve plexuses in adrenal medulla was
      significantly increased by 30 years of age due to the development of nervous
      relations in this organ. After age of 30 years density of nerve plexuses in
      adrenal medulla remained relatively stable providing high morphofunctional
      activity of adrenal glands. Morphological and morphometrical changes in nervous
      plexuses of adrenal medulla of patients were associated with cardiovascular
      diseases.

PMID- 16883269
TI  - [Calcification of the aortic valve and bone metabolism in the elderly].

PMID- 16883270
TI  - [Pharmacogenetics of indirect anticoagulants: value of genotype for improvement
      of efficacy and safety of therapy].
AB  - The review is devoted to the contemporary state of the problem of
      pharmacogenetics of indirect anticoagulants. At present there are data about
      effects of allele variants of CYP2C9, VKORC1, APOE genes on efficacy and safety
      of therapy with indirect anticoagulants. Detection of these variants is a
      perspective way to individualization of therapy with indirect anticoagulants.

PMID- 16883271
TI  - [Moexipril and cardiovascular diseases in women: is there a reason for
      optimism?].
AB  - Angiotensin converting enzyme (ACE) inhibitors are first line preparations in the
      treatment of chronic heart failure irrespective of etiology. However there are
      numerous proofs that in women drugs of this group exert less pronounced favorable
      prognostic influence compared with men. Moexipril is an ACE inhibitor which in
      women demonstrated its doubtless antihypertensive efficacy with additional
      favorable properties. The study of efficacy of moexipril in chronic heart failure
      in women is able to broaden indications to the use of this drug.

PMID- 16883273
TI  - Contribution of cattle farms towards river contamination with Giardia cysts and
      Cryptosporidium oocysts in Sungai Langat Basin.
AB  - A study to determine the contribution of Giardia cysts and Cryptosporidium
      oocysts from cattle farms was carried out at the Langat Basin. This study
      investigated the contribution of cattle farms, located near Sungai Langat and
      Sungai Semenyih, towards river contamination with these cysts and oocysts. The
      findings showed that out of 24 samples of water taken from Sungai Semenyih, 4.2%
      was positive for Giardia cysts with a concentration of 1.3 cysts/L and 20.8% were
      positive with Cryptosporidium oocysts with a range of 0.7 - 2.7 oocysts/L. At
      Sungai Langat, from the 43 samples taken, 23.3% were positive for Giardia cysts
      with a range of 1.5 - 9 cysts/L whereas 11.6% were positive with Cryptosporidium
      oocysts with a range of 2.5 - 240 oocysts/L. Isolation of cysts and oocysts in
      bovine faecal materials revealed that 14.6% of faecal samples were positive for
      Giardia cysts which had a range of 75 - 1.3x104 cysts/g and 25% were positive for
      Cryptosporidium oocysts with a range of 50 - 3.9x105 oocysts/g. From the cattle
      wastewater, 98% were positive with oocysts and 6.7% with cysts. The
      concentrations were between 20 - 3.1x103 oocysts/mL for Cryptosporidium and 4 -
      75 cysts/mL for Giardia. Given that the prevalence of Cryptosporidium and Giardia
      are high amongst the cattle and the positive findings of the (oo)cysts in the
      river samples, it could be deduced that there is a very high possibility of the
      cattle farms contaminating the river with Giardia cysts and Cryptosporidium
      oocysts. Viability study of Cryptosporidium oocysts in the surrounding soil and
      pond within the cattle farm showed that the viability of Cryptosporidium oocysts
      decreased with time. It was estimated that it will take 52 days for all the
      oocysts from both environment to be non-viable. With a viability rate of
      approximately 2 months in a cattle farm setup, river water contaminated with
      Cryptosporidium oocysts has a high chance of acting as an agent of transmission.
      As cattle farms are also inhabited by the owners and their families, this problem
      may pose a threat to humans (e.g. children) especially if they are dependent on
      the river water as their source of water for their daily activities.

PMID- 16883274
TI  - Cytotoxic activities of chemical constituents from Mesua daphnifolia.
AB  - Detail chemical investigations on the stem bark of Mesua daphnifolia gave three
      triterpenoids and four xanthones. They are friedelin (1), friedelan-1,3-dione
      (2), lup-20(29)- en-3ss-ol (3), cudraxanthone G (4), ananixanthone (5), 1,3,5
      trihydroxy-4-methoxyxanthone (6) and euxanthone (7). These chemical constituents
      were tested in vitro for their cytotoxic activities against four cell lines, MDA
      MB-231 (human estrogen receptor negative breast cancer), HeLa (cervical
      carcinoma), CEM-SS (T-lymphoblastic leukemia) and CaOV3 (human ovarian cancer).
      Compound 4 showed a broad spectrum of activity against the MDA-MB-231, HeLa and
      CEM-SS cell lines with IC5 0 values of 1.3, 4.0 and 6.7 microg/ml respectively.
      Meanwhile, the other compounds 1, 2, 3, 5, 6 and 7 gave only selective activities
      against the cell lines.

PMID- 16883275
TI  - Resistance development and insecticide susceptibility in Culex quinquefasciatus
      against selection pressure of malathion and permethrin and its relationship to
      cross-resistance towards propoxur.
AB  - To determine resistance level and characterize malathion and permethrin
      resistance in Culex quinquefasciatus, two methods were used namely: WHO
      procedures of larval bioassay to determine the susceptibility of lethal
      concentration (LC) and adult bioassay to determine the lethal time (LT) which are
      resistant to malathion and permethrin. These mosquito strains were bred in the
      Insectarium, Division of Medical Entomology, IMR. Thousands of late fourth instar
      larvae which survived the selection pressure to yield 50% mortality of malathion
      and permethrin were reared and colonies were established from adults that
      emerged. Larvae from these colonies were then subjected to the subsequent 10
      generations in the test undertaken for malathion resistant strain (F61 - F70) and
      permethrin resistant strain (F54 - F63). Selection pressure at 50% - 70%
      mortality level was applied to the larvae of each successive generation. The rate
      of resistance development and resistance ratio (RR) were calculated by LC5 0 for
      larval bioassay and LT50 value for adult bioassay. The lab bred Cx.
      quinquefasciatus was used as a susceptible strain for comparison purpose. The
      adult bioassay test was carried out by using diagnostic dosages of malathion
      5.0%, permethrin 0.75% and with propoxur 0.1%. All bioassay results were
      subjected to probit analysis. The results showed that LC5 0 for both malathion
      (F61 - F70) and permethrin (F54 - F63) resistant Cx. quinquefasciatus increased
      steadily to the subsequent 10 generations indicating a marked development of
      resistance. The adult female malathion resistant strain have developed high
      resistance level to malathion diagnostic dosage with resistance ratio 9.3 to 9.6
      folds of resistance. Permethrin resistance ratio remained as 1.0 folds of
      resistance at every generation. It was obvious that malathion resistance
      developing at a higher rate in adult females compared to permethrin. Female
      adults exposed to 2 hours of exposure period for propoxur 0.1% showed presence of
      cross-resistance among the both strains of mosquitoes towards propoxur and it was
      indicated by 70%-100% mortality at 24 hours post-recovery period.

PMID- 16883276
TI  - Partial characterization of genes encoding the ATP-binding cassette proteins of
      Cryptosporidium parvum.
AB  - The present study aims to explore the possible mechanisms underlying the
      multidrug resistance characteristic of Cryptosporidium parvum by detecting the
      presence of ATP-binding cassette (ABC) protein encoding genes, especially one
      that shows high similarity to members belonging to the multidrug resistance
      protein (MDR) and multidrug resistance associated protein (MRP) subfamilies. PCR
      using ABC-specific degenerate primers successfully amplified two unique
      fragments, designated Cpnbd1 and Cpnbd2, from C. parvum genomic DNA. Cpnbd1
      exhibited high degree of homology (99-100%) with the nucleotide- binding domains
      (NBDs) at the NH2 -terminal halves of two previously reported ABC proteins (CpABC
      and CpABC1) of human and bovine origin C. parvum isolates. It is likely that
      CpABC, CpABC1 and Cpnbd1 were encoded by homologous genes of a type of ABC
      transporter protein found in different C. parvum isolates. However, Cpnbd2 showed
      moderate levels of similarities (28-49%) to the NBDs of four ABC proteins
      characterised in C. parvum to date. Therefore, Cpnbd2 could be a novel member of
      an ABC superfamily of proteins in C. parvum. Phylogenetic analyses on a list of
      ABC transporters known to associate with MDR phenotype has significantly linked
      Cpnbd1 and Cpnbd2 to these transporters, thus suggesting that Cpnbd1 and Cpnbd2
      proteins may contribute to the intrinsic multidrug resistance phenotype of C.
      parvum.

PMID- 16883277
TI  - Polymorphic and sex-limited phosphoglucomutase in Parastrongylus cantonensis
      (Nematoda: Angiostrongylidae).
AB  - Phosphoglucomutase was studied by polyacrylamide gel electrophoresis in the
      Thailand and Hawaii isolates of Parastrongylus cantonensis (also known as
      Angiostrongylus cantonensis). Two loci were present. The faster-moving locus (PGM
      1) was polymorphic in the Hawaii isolate, represented by two alleles - the faster
      moving, less common Pgm-1A and the slower-moving, more common Pgm-1B . It was
      monomorphic for the faster-moving allele Pgm-1A in the Thailand isolate. The
      slower-moving locus (PGM-2) was invariant, with a single band of enzyme activity,
      in the female worms of both the Thailand and Hawaii isolates. There was no
      detectable enzyme activity at this PGM-2 locus in the male worms of both
      isolates. The non-expression or 'null' PGM-2 phenotype in the male worms was
      presumed to be sex- limited. The present findings differ significantly in several
      aspects (polymorphic locus, proportion of polymorphic loci, heterozygosity,
      deviations from Hardy-Weinberg expectations, sex-limited expression) from the
      Japan isolate of P. cantonensis reported in the literature.

PMID- 16883278
TI  - Haemonchus contortus: parasite problem No. 1 from tropics - Polar Circle.
      Problems and prospects for control based on epidemiology.
AB  - There is no doubt that on a global basis, Haemonchus contortus is by far the most
      important parasite of small ruminants (sheep and goats). This is particularly
      more so now, with the development of high levels of resistance to both the broad
      and narrow spectrum anthelmintic drugs in H. contortus throughout the world.
      Epidemiological studies describe the lower environmental limits for haemonchosis
      to occur in sheep, as being a mean monthly temperature of 18C and approximately
      50mm rainfall. Thus it has been generally recognised that H. contortus is a
      problem parasite restricted to the warm, wet countries where sheep and goats are
      raised. However, recent evidence shows that this parasite is apparently common
      even in northern Europe. Thus the need for sustainable control strategies for H.
      contortus is becoming much more pressing. This report highlights two examples of
      sustainable and highly efficient control programmes for H. contortus, that can be
      implemented in regions at the extremes of its geographic range (Malaysia and
      Sweden), where the authors have had direct involvement.

PMID- 16883279
TI  - Repellency of volatile oils from Moschosma polystachyum and Solanum xanthocarpum
      against filarial vector Culex quinquefasciatus say.
AB  - Volatile oils extracted by steam distillation from leaves of two plant species
      Moschosma polystachyum and Solanum xanthocarpum were evaluated in mosquito cages
      for their topical repellency effects against filarial vector Culex
      quinquefasciatus. The oil from M. polystachyum was tested at four different
      concentrations ranging from 1 to 4%. The 4% concentration gave 332.2 minutes
      protection whereas control gave only 4.4 minutes protection against mosquito
      bites. However, the volatile oil of S.xanthocarpum was tested from 2 to 8%
      concentration. The 8% concentration gave 311.4 minutes protection whereas control
      gave only 4.4 minutes protection against mosquito bites. The results suggest that
      the volatile oils of these two plant species were effective as repellents and
      gave more than 300 minutes of (>5 hour) protection against the bite of Cx.
      quinquefasciatus bite. Both volatile oils did not cause dermal irritation when
      applied to human skin. No adverse effects on human volunteers were observed after
      application. Therefore, both volatile oils can be applied as an effective
      personal protection measure against mosquito bites.

PMID- 16883281
TI  - Rapid detection of chikungunya virus in laboratory infected Aedes aegypti by
      Reverse-Transcriptase- Polymerase Chain Reaction (RT-PCR).
AB  - A study of chikungunya virus was carried out to establish Reverse Transcriptase-
      Polymerase Chain Reaction (RT-PCR) as a rapid detection technique of the virus.
      The susceptibility of lab-colonized Aedes aegypti to chikungunya virus was also
      determined. Artificial membrane feeding technique was used to orally feed the
      mosquitoes with a human isolate of chikungunya virus. A total of 100 fully
      engorged female Ae. aegypti were obtained and maintained for 7 days. Seventy of
      them survived and then pooled at 10 individuals per pool. Total RNA was extracted
      from the samples and RT-PCR amplifications were carried out. Five out of 7 pools
      showed positive PCR band at 350-bp, indicating Ae. aegypti is a potential vector
      of chikungunya virus. The minimum infection rate (MIR) was 71% within these
      laboratory colonies. RT-PCR is a sensitive technique that is useful in detecting
      infected mosquitoes in epidemic areas. This technique can de used as a rapid
      detection method and provide an early virologic surveillance systems of
      chikungunya virus infected mosquitoes.

PMID- 16883280
TI  - Field bioefficacy of deltamethrin residual spraying against dengue vectors.
AB  - Field bioefficacy of residual-sprayed deltamethrin against Aedes vectors was
      evaluated in an urban residential area in Kuala Lumpur. The trial area consisted
      of single storey wood-brick houses and a block of flat. The houses were treated
      with outdoor residual spraying while the flat was used as an untreated control.
      Initial pre-survey using ovitrap surveillance indicated high Aedes population in
      the area. Deltamethrin WG was sprayed at a dosage of 25mg/m2 using a compression
      sprayer. The effectiveness of deltamethrin was determined by wall bioassay and
      ovitrap surveillance. The residual activity of 25mg/m2 deltamethrin was still
      effective for 6 weeks after treatment, based on biweekly bioassay results.
      Bioassay also indicated that both Aedes aegypti and Aedes albopictus were more
      susceptible on the wooden surfaces than on brick. Aedes aegypti was more
      susceptible than Ae. albopictus against deltamethrin. Residual spraying of
      deltamethrin was not very effective against Aedes in this study since the Aedes
      population in the study area did not reduce as indicated by the total number of
      larvae collected using the ovitrap (Wilcoxon Sign Test, p> 0.05). Further studies
      are required to improve the effectiveness of residual spraying against Aedes
      vectors.

PMID- 16883282
TI  - Effect of Eurycoma longifolia extract on the Glutathione level in Plasmodium
      falciparum infected erythrocytes in vitro.
AB  - In the present study we examined the effect of E. longifolia methanol extract
      (TA164) on the GSH levels of P. falciparum infected erythrocytes and uninfected
      erythrocytes. Our study on parasite growth shows the IC50 and IC75 values of
      TA164 to be 0.17 g/ml and 6 g/ml respectively while for BSO was 25.5 g/ml and
      46.5 g/ml respectively. About 95% to 100% growth inhibition of P. falciparum
      infected erythrocyte was observed when treated with TA164 and BSO at 16 g/ml and
      64 g/ml respectively. The study on GSH contents indicated that non-infected
      erythrocytes treated with 6 g/ml (IC75 values) of TA164 at 24 hours incubation
      showed less GSH content as compared to non-treated erythrocytes. A similar
      observation was seen on treated trophozoite infected erythrocyte (10%
      parasitemia) when treated with 6 g/ml at 3 hours incubation. Analysis of the GSH
      contents of parasite compartments treated with TA164 at the same concentration (6
      g/ml) for 3 hours incubation indicated a reduction of GSH contents. At the same
      concentration, TA164 did not affect the GSH contents of enriched trophozoite
      infected erythrocytes (60-70% parasitemia). TA164 did affect the GSH content of
      non-infected erythrocyte at 24 hours (accept IC50 value) as well as the parasite
      compartments (trophozoite infected erythrocyte and parasite itself) but fails to
      affect the GSH content of enriched trophozoite infected erythrocyte.

PMID- 16883284
TI  - Identification of major allergens of two species of local snappers: Lutjanus
      argentimaculatus (merah/ red snapper) and Lutjanus johnii (jenahak/ golden
      snapper).
AB  - Fish has been recognized as a source of potent allergens both in food and
      occupational allergy. Lutjanus argentimaculatus (red snapper) and Lutjanus johnii
      (golden snapper) locally known as merah and jenahak, respectively, are among the
      most commonly consumed fish in Malaysia. The objective of this study is to
      identify the IgE-binding proteins and major allergens of these species of fishes.
      Extracts of both fish species were prepared and fractionated by sodium dodecyl
      polyacrylamide gel electrophoresis (SDS-PAGE). IgE binding patterns were then
      demonstrated by immunoblotting using sera from patients allergic to the fishes.
      The raw extracts of both fish produced 26 protein bands. Both species of fishes
      had similar protein profiles. In cooked extracts, several protein bands in the
      range of about 40 to 90 kD which were present in the uncooked extracts appeared
      to be denatured and formed high molecular weight complexes. The immunoblotting of
      golden snapper and red snapper revealed 16 and 15 various IgE-binding bands, in
      the range of 151 to 12-11 kD, respectively. A 51 kD protein was identified as a
      major allergen for both fishes. A 46 kD protein was also demonstrated as a major
      allergen in golden snapper and a 42 kD protein was also seen as a major allergen
      in red snapper. A heat-resistant protein of ~12 kD which is equivalent in size
      with fish parvalbumin was demonstrated only as minor allergen for both fishes.

PMID- 16883283
TI  - In vitro screening of five local medicinal plants for antibacterial activity
      using disc diffusion method.
AB  - Medicinal plants have many traditional claims including the treatment of ailments
      of infectious origin. In the evaluation of traditional claims, scientific
      research is important. The objective of the study was to determine the presence
      of antibacterial activity in the crude extracts of some of the commonly used
      medicinal plants in Malaysia, Andrographis paniculata, Vitex negundo, Morinda
      citrifolia, Piper sarmentosum, and Centella asiatica. In this preliminary
      investigation, the leaves were used and the crude extracts were subjected to
      screening against five strains of bacteria species, Methicillin Resistant
      Staphylococcus aureus (MRSA), Staphylococcus aureus, Klebsiella pneumoniae,
      Pseudomonas aeruginosa and Escherichia coli, using standard protocol of Disc
      Diffusion Method (DDM). The antibacterial activities were assessed by the
      presence or absence of inhibition zones and MIC values. M. citrifolia, P.
      sarmentosum and C. asiatica methanol extract and A. paniculata (water extract)
      have potential antibacterial activities to both gram positive S. aureus and
      Methicillin Resistant S. aureus (MRSA). None of the five plant extracts tested
      showed antibacterial activities to gram negative E. coli and K. pneumoniae,
      except for A. paniculata and P. sarmentosum which showed activity towards P.
      aeruginosa. A. paniculata being the most potent at MIC of 2 g/disc. This finding
      forms a basis for further studies on screening of local medicinal plant extracts
      for antibacteria properties.

PMID- 16883285
TI  - IgE-mediated hypersensitivity reaction to lignocaine - a case report.
AB  - We report a 7 year old girl who developed ipsilateral left facial swelling
      immediately after lignocaine injection. Skin prick test showed positive reaction
      to pure 2% lignocaine hydrochloride and to lignocaine oral dental gel. Specific
      Immunoglobulin E (Ig E) to lignocaine was detected. Lignocaine is a commonly used
      anaesthetic agent mainly as local anaesthesia. However type I hypersensitivity to
      lignocaine is rare and there have been very few cases reported in the literature.

PMID- 16883286
TI  - Sterilisation of Lucilia cuprina Wiedemann maggots used in therapy of intractable
      wounds.
AB  - Three new techniques of sterilising maggots of Lucilia cuprina for the purpose of
      debriding intractable wounds were studied. These techniques were utilisation of
      ultra-violet C (UVC) and maggot sterilisation with disinfectants. The status of
      sterility was checked on nutrient agar and blood agar and confirmed with
      staining. The indicators for the effectiveness of the methods were sterility and
      survival rate of the eggs or larvae. Egg sterilisation with UVC had the lowest
      hatching rate (16+/-0.00%) while egg sterilisation with disinfectants showed high
      hatching rate (36.67+/-4.41%) but low maggot survival rate (31.67+/-1.67%).
      Sterilisation of the maggots was the most suitable, since the survival rate was
      the highest (88.67+/-0.88%). Complete sterility was achieved in all cases, except
      that Proteus mirabilis was consistently found. However, the presence of this
      microorganism was considered beneficial.

PMID- 16883287
TI  - Helminth infections in small mammals from Ulu Gombak Forest Reserve and the risk
      to human health.
AB  - A survey for small mammal parasites carried out in a secondary forest of Ulu
      Gombak, Selangor, Peninsula Malaysia yielded the following animals: Rattus
      bowersi (7), Rattus tiomanicus jalorensis (2), Maxomys rajah (12), Maxoyms
      whiteheadi (3), Leopoldamys sabanus(13), Sundamys muelleri(10), Lariscus insignis
      (1), Sundasciurus tenuis (1) and Tupaia glis (2). The following nematodes:
      Capillaria hepatica, Hepatojarakus malayae, Trichostrongylus sp. and
      Streptopharagus sp., the following cestodes: Hymenolepis sp., Raillietina sp. and
      Taenia taeniaformis; and trematode, Zonorchis sp. from Tupaia glis were
      recovered. No parasites were observed during blood examination. No endoparasite
      was seen in Maxomys whiteheadi, Lariscus insignis and Sundasciurus tenuis. The
      following parasites, Capillaria hepatica, Hymenolepis sp., Raillietina sp. and
      Taenia taeniaformis are considered of medical importance.

PMID- 16883288
TI  - Weekly variation on susceptibility status of Aedes mosquitoes against temephos in
      Selangor, Malaysia.
AB  - Larvae of Aedes aegypti and Aedes albopictus obtained from 6 consecutive ovitrap
      surveillance (OS) in Taman Samudera and Kg. Banjar were evaluated for their
      susceptibility to temephos. Larval bioassays were carried out in accordance with
      WHO standard methods, with diagnostic dosage (0.012 mg/L) and operational dosage
      (1 mg/L) of temephos respectively. Aedes aegypti and Ae. albopictus obtained from
      six OS in Taman Samudera showed resistance to diagnostic dosage of temephos with
      percentage mortality between 5.3 to 72.0 and 9.3 to 56.0, respectively, while Ae.
      aegypti and Ae. albopictus obtained from Kg. Banjar showed resistance to temephos
      with percentage mortality between 16.0 to 72.0 and 0 to 50.6, respectively. Only
      two strains of Ae. aegypti from Kg. Banjar were susceptible to temephos with
      93.3% (OS 2) and 100% (OS 3) mortality. The 50% mortality at lethal time (LT50)
      for all strains of Ae. aegypti and Ae. albopictus tested against operational
      dosage of temephos showed range between 36.07 to 75.69 minutes and 58.65 to
      112.50 minutes, respectively, and complete mortality was achieved after 24 hours.
      Our results indicated that there is weekly variations of the resistance status
      for Ae. aegypti and Ae. albopictus. Aedes susceptibility to temephos is changing
      from time to time in these two study sites. It is essential to continue
      monitoring the resistance of this vector to insecticides in order to ensure the
      efficiency of program aimed at vector control and protection of human health.

PMID- 16883289
TI  - Susceptibility of Aedes aegypti and Aedes albopictus to temephos in four study
      sites in Kuala Lumpur City Center and Selangor State, Malaysia.
AB  - Larvae obtained from Taman Samudera (Gombak, Selangor), Kampung Banjar (Gombak,
      Selangor), Taman Lembah Maju (Cheras, Kuala Lumpur) and Kampung Baru (City
      centre, Kuala Lumpur) were bioassayed with diagnostic dosage (0.012 mg/L) and
      operational dosage (1 mg/L) of temephos. All strains of Aedes aegypti and Aedes
      albopictus showed percentage mortality in the range of 16.00 to 59.05 and 6.4 to
      59.50 respectively, after 24 hours. LT50 values for the 6 strains of Ae. aegypti
      and Ae. albopictus were between 41.25 to 54.42 minutes and 52.67 to 141.76
      minutes respectively, and the resistance ratio for both Aedes species were in the
      range of 0.68 to 1.82 when tested with operational dosage, 1 mg/L temephos. These
      results indicate that Aedes mosquitoes have developed some degree of resistance.
      However, complete mortality for all strains were achieved after 24 hours when
      tested against 1 mg/L temephos.

PMID- 16883290
TI  - Sensitivity of Aedes albopictus C6/36 cells line for the detection and
      infectivity titration of dengue virus.
AB  - Plaque assay procedure was carried out to determine the infectivity titration of
      dengue virus using Aedes albopictus C6/36 mosquito cell line. Cells were seeded
      in 6 wells plates and incubated until monolayer C6/36 cell lines were formed.
      Each well was exposed to a different dilution of dengue infected culture fluid,
      followed by addition of first and second overlay medium. Cells were observed
      under an inverted microscope and plaque staining was carried out. The results
      showed that countable plaques were not achieved and plaques formed were
      restricted to the central section due to the significant partial lysis of the
      C6/36 cells in the plates. However, the plaque assay technique using C6/36 cell
      line reported here appears to be promising and merits further detailed studies.

PMID- 16883291
TI  - Rhinocort vs Eltair: a comparative review of a patented and generic drug.
AB  - Rhinocort and Eltair are both the patented and generic equivalent of the topical
      nasal steroid budesonide. A study consisting of 42 patients was conducted at the
      ENT department of Hospital Ipoh to compare the response of patients who were
      using Rhinocort prior to Eltair. The results show statistically significant
      symptomatic response and lower complications with Rhinocort compared to Eltair.

PMID- 16883292
TI  - Bacteria fauna from the house fly, Musca domestica (L.).
AB  - The house fly, Musca domestica has long been considered a potential agent for
      disease transmission ever since its existence. The general truth of this
      assertion remains undisputed till the present day in spite of increasing
      awareness toward an improved sanitation and better hygiene. The habitual movement
      of house fly from filthy substrata such as human faeces, animal excreta,
      carcasses, garbage, etc. makes them ideal candidates for disease transmission
      such as cholera, shigellosis, salmonellosis and others when settling on food. Fly
      as a potential mechanical vector of pathogenic bacteria was elucidated in this
      study by examining flies from various breeding sites such as food courts, dumping
      ground, food processing areas and poultry farm in Peninsular Malaysia. The flies
      were baited with 10% sugar solution on a glass slide in the field. All materials
      used for collection of samples were sterile. Bacteria from fly sample were
      isolated using the normal isolation technique. Bacillus sp., Coccobacillus sp.,
      Staphylococcus sp., Microccus sp., Streptococcus sp., Acinetobacter sp.,
      Enterobacter sp., Proteus sp., Escherichia sp., Klebsiella sp. and yeast cells
      were isolated from feaces, vomitus, external surfaces and internal organs of
      house fly. Newly emerged house fly did not harbour any bacteria.

PMID- 16883293
TI  - Protein synthesized by dengue infected Aedes aegypti and Aedes albopictus.
AB  - The main objective of this study was to compare protein profiles of whole
      mosquitoes of Malaysian Aedes aegypti and Aedes albopictus after infection with
      virus and to investigate whether dengue virus would induce protein secretion in
      Ae. aegypti and Ae. albopictus. Using SDS -PAGE, it was shown that in uninfected
      Ae. aegypti and Ae. albopictus, the protein bands were within the range of 14 -
      80 kDa with most of the bands overlapping for the two species. Comparison of the
      protein profile of infected and uninfected Ae. aegypti and Ae. albopictus showed
      five distinct molecular weight grouping at 73 - 76 kDa (Group 1), 44 - 50 kDa
      (Group 2), 28 - 31 kDa (Group 3), 20 - 25 kDa (Group 4) and 14 - 17 kDa (Group
      5). Predominant bands for both species (infected and uninfected) were between 21 
      25 kDa and 44 - 50 kDa. Protein bands having a molecular weight of 70 kDa were
      only present in infected Ae. albopictus and those bands having molecular weight
      of 21 kDa were observed only in infected Ae. aegypti. The rate of digestion of
      blood meals was more rapid in Ae. albopictus than Ae. aegypti. Uninfected Ae.
      albopictus completed the blood digestion 2 days after ingestion of a blood meal
      whereas Ae. aegypti needed 3 days to complete the digestion. The rate of
      digestion for blood meals was slower for both mosquito species when fed with
      dengue virus infected blood. The digestion processes were completed 3 and 4 days
      after blood ingestion for Ae. albopictus and Ae. aegypti, respectively. This
      could be due to the presence of dengue virus in the blood, which slow down the
      digestion process. Appearance and disappearance of new protein bands was also
      observed even after the digestion has completed for both infected mosquito
      species. In conclusion, dengue virus was shown to induce specific proteins in
      both Ae. aegypti and Ae. albopictus.

PMID- 16883294
TI  - A preliminary survey of ectoparasites of small mammals in Kuala Selangor Nature
      Park.
AB  - Trapping of small mammals was conducted at 5 study sites in Kuala Selangor Nature
      Park (KSNP) from 20-24 June 2005. A total of 11 animals comprising 2 species of
      rodents, Maxomys whiteheadi and Rattus exulans were caught from 3 sites, i.e from
      an area of mixed secondary forest and mangrove swamp; an area of mangrove swamp,
      and from an area of lalang fringing mangrove swamp. From these animals, the
      following 7 species of ectoparasites were found: Laelaps echidninus, Laelaps
      nuttalli, Ascoschoengastia indica, Leptotrombidium deliense, Hoplopleura
      pectinata, Hoplopleura pacifica and Polyplax spinulosa. One of the ectoparasites
      found, L. deliense is a known vector of scrub typhus and thus may pose potential
      health risks to visitors to KSNP.

PMID- 16883295
TI  - A comparative study of adult mosquito trapping using dry ice and yeast generated
      carbon dioxide.
AB  - Adult mosquito collections were conducted for 12 weeks in two residential areas
      in Kuala Lumpur. The CDC light traps were compared using dry ice and yeast as
      sources of carbon dioxide attractants for mosquitoes. The efficacy of the dry ice
      baited trap was significant over yeast generated CO2 trap. The predominant
      species obtained were Culex quinquefasciatus, Stegomyia albopicta and Armigeres
      subalbatus.

PMID- 16883296
TI  - In utero exposure to diesel exhaust increased accessory reproductive gland weight
      and serum testosterone concentration in male mice.
AB  - The effects of in utero exposure to diesel exhaust (DE) on the male mouse
      reproductive system were examined. Pregnant ICR mice inhaled DE at soot
      concentrations of 0.3, 1.0, or 3.0 mg DEP/m3 or clean air as the control, for 2
      16 days postcoitum. On postnatal day (PND) 28, the weights of the testes and
      accessory glands and testosterone concentration in serum were significantly
      higher in the DE-exposed male pups. Testosterone concentration correlated
      significantly (P<0.01) with the expression levels of steroidogenic enzyme mRNAs,
      weights of the testes and male reproductive accessory glands, and daily sperm
      production. These findings indicate that very early stage mouse embryo exposure
      to DE leads to endocrine disruption after birth and acceleration of male puberty.

PMID- 16883297
TI  - Toenail arsenic levels among residents in Amami-Oshima Island, Japan.
AB  - In order to evaluate the current arsenic exposure status and its determinants in
      Japan, we collected toenail samples from 212 subjects residing in a town with a
      population of 6,900 in Amami-Oshima Island in August 1999. We measured arsenic
      concentrations of the toenails using inductively coupled plasma mass
      spectrometry. In addition, we examined the association of arsenic levels with
      lifestyles and dietary habits, including the consumption of fish, seaweed, and
      rice. The mean toenail arsenic level was 0.41 ppm (95% confidence interval, 0.36
      0.47), which was about 3-fold higher than those observed in other populations of
      mainland Kagoshima. Arsenic levels were elevated among current smokers (mean =
      0.65; 95% confidence interval, 0.32-1.29) when compared with non-smokers (mean =
      0.40; 95% confidence interval, 0.34-0.46), and among the residents consuming 4
      bowls or more, of rice every day (mean = 1.97; 95% confidence interval, 0.25
      15.75) when compared to residents consuming 3 bowls or less (mean = 0.39; 95%
      confidence interval, 0.34-0.45). Sex, age, alcohol intake, fish consumption, or
      seaweed consumption was not associated with toenail arsenic concentration.
      Further studies seem warranted to examine the cause of relatively high arsenic
      levels in our study area.

PMID- 16883298
TI  - Availability of in vitro vitellogenin assay for screening of estrogenic and anti
      estrogenic activities of environmental chemicals.
AB  - Vitellogenin (VTG) protein, VTG mRNA, other egg yolk proteins, vitelline envelope
      proteins and their mRNAs are produced in the liver of oviparous species by
      stimulation of endogenous estrogen and exogenous estrogenic chemicals. The VTG
      assay based on enzyme-linked immunosorbent assay (ELISA) has been widely used for
      many fish species to screen estrogenic and anti-estrogenic activities of
      chemicals and sewage effluents using immature fish and/or male fish. In order to
      reduce the number of fish for screening of estrogenicity and anti-estrogenicity
      of chemicals, primary cultured fish hepatocytes can be used. In fact, primary
      cultured hepatocytes have been successfully used for the detection of estrogenic
      and anti-estrogenic activities of environmental chemicals in selected OECD fish
      species, e.g., medaka (Oryzias latipes) and rainbow trout (Oncorhynchys mykiss)
      together with other fish species such as Atlantic salmon (Salmo salar L.),
      Siberian sturgeon (Acipenser baeri), tilapia (Oreochromis mossambicus), carp
      (Cyprinus carpio), bream (Abramis brama), Carassius auratus, silver eel (Anguilla
      anguilla L.), and channel catfish (Ictalurus punctanus). In terms of hepatocyte
      assays relating to other taxa, these include frogs such as Xenopus laevis and the
      common green frog (Rana esculenta), chickens (Gallus domesticus) and herring
      gulls (Larus argentatus). VTG mRNA measurement by quantitative reverse
      transcription-polymerase chain reaction has also been successfully applied in the
      primary cultured hepatocytes of various species.

PMID- 16883299
TI  - International spinal research trust research strategy. III: A discussion
      document.
AB  - STUDY DESIGN: Discussion document. OBJECTIVES/METHODS: To review the Research
      Strategy of the International Spinal Research Trust (ISRT), which identifies key
      areas of basic and clinical research that are likely to be beneficial in
      developing potential treatments for spinal cord injury for funding. This strategy
      is intended to both guide the programme of research towards areas of priority and
      stimulate discussion of the different avenues of research. This latest document
      has been developed to take into account the scientific progress in the 6 years
      since publication of the previous Research Strategy. RESULTS/DISCUSSION: The
      latest scientific developments in research designed to repair the spinal cord and
      restore function following injury and how they might impact on spinal cord injury
      research are highlighted.

PMID- 16883300
TI  - Pine-site myiasis: a rare complication of halo orthosis.

PMID- 16883301
TI  - Case histories, magic bullets and the state of drug discovery.
AB  - The case histories of five modern drugs are taken as a basis for reflection on
      the state of drug discovery. Two issues intimately associated with drug research
      are highlighted: the nature of the intellectual process leading to new
      discoveries; and the possibility that the principle of selective efficacy, which
      has guided drug research from its beginnings, might need modification, at least
      in some areas of pharmacotherapy.

PMID- 16883302
TI  - Applying the concepts of financial options to stimulate vaccine development.
AB  - Stimulating research and development for neglected diseases (such as
      tuberculosis, malaria and AIDS) has proven difficult. We offer an alternative
      approach to stimulating research into neglected diseases based on the concept of
      a financial call option. Our Call Options for Vaccines (COV) model allows the
      purchaser to make payments during the early stages of development in exchange for
      reduced future prices. We conclude with a discussion of possible risks and
      benefits.

PMID- 16883303
TI  - Strategies for optimizing combinations of molecularly targeted anticancer agents.
AB  - The rapid emergence of hundreds of new agents that modulate an ever-growing list
      of cancer-specific molecular targets offers tremendous hope for cancer patients.
      However, evaluating targeted agents individually, in combination with standard
      treatments, and in combination with other targeted agents presents significant
      development challenges. Because the number of possible drug combinations is
      essentially limitless, a strategy for determining the most promising combinations
      and prioritizing their evaluation is crucial. Here, we consider the crucial
      elements of a development strategy for targeted-agent combinations. Issues that
      pose challenges to the rational preclinical and clinical evaluation of such
      combinations will be described, and possible approaches to overcoming these
      challenges will be discussed.

PMID- 16883304
TI  - Phosphodiesterases in the CNS: targets for drug development.
AB  - The therapeutic and commercial success of phosphodiesterase 5 inhibitors such as
      Viagra, Levitra and Cialis has sparked renewed interest in the phosphodiesterases
      as drug discovery targets. Virtually all the phosphodiesterases are expressed in
      the CNS, making this gene family a particularly attractive source of new targets
      for the treatment of psychiatric and neurodegenerative disorders. Significantly,
      all neurons express multiple phosphodiesterases, which differ in cyclic
      nucleotide specificity, affinity, regulatory control and subcellular
      compartmentalization. Therefore, phosphodiesterase inhibition represents a
      mechanism through which it could be possible to precisely modulate neuronal
      activity. In this article, we review the current state of the art in the
      burgeoning field of phosphodiesterase pharmacology in the CNS.

PMID- 16883305
TI  - Current development of mTOR inhibitors as anticancer agents.
AB  - Mammalian target of rapamycin (mTOR) is a kinase that functions as a master
      switch between catabolic and anabolic metabolism and as such is a target for the
      design of anticancer agents. The most established mTOR inhibitors--rapamycin and
      its derivatives--showed long-lasting objective tumour responses in clinical
      trials, with CCI-779 being a first-in-class mTOR inhibitor that improved the
      survival of patients with advanced renal cell carcinoma. This heralded the
      beginning of extensive clinical programmes to further evaluate mTOR inhibitors in
      several tumour types. Here we review the clinical development of this drug class
      and look at future prospects for incorporating these agents into multitarget or
      multimodality strategies against cancer.

PMID- 16883306
TI  - Sildenafil: from angina to erectile dysfunction to pulmonary hypertension and
      beyond.
AB  - In less than 20 years, the first selective type 5 phosphodiesterase inhibitor,
      sildenafil, has evolved from a potential anti-angina drug to an on-demand oral
      treatment for erectile dysfunction (Viagra), and more recently to a new orally
      active treatment for pulmonary hypertension (Revatio). Here we describe the key
      milestones in the development of sildenafil for these diverse medical conditions,
      discuss the advances in science and clinical medicine that have accompanied this
      journey and consider possible future indications for this versatile drug.

PMID- 16883307
TI  - An utter refutation of the "Fundamental Theorem of the HapMap" by Terwilliger and
      Hiekkalinna.

PMID- 16883309
TI  - The origin and specification of cortical interneurons.
AB  - GABA-containing interneurons are crucial to both the development and function of
      the cerebral cortex. Unlike cortical projection neurons, which have a relatively
      conserved set of characteristics, interneurons include multiple phenotypes that
      vary on morphological, physiological and neurochemical axes. This diversity, and
      the relatively late, context-dependent maturation of defining features, has
      challenged efforts to uncover the transcriptional control of cortical interneuron
      development. Here, we discuss recent data that are beginning to illuminate the
      origins and specification of distinct subgroups of cortical interneurons.

PMID- 16883308
TI  - The challenges of Proteus syndrome: diagnosis and management.
AB  - Proteus syndrome (PS) is a disorder of patchy or mosaic postnatal overgrowth of
      unknown etiology. The onset of overgrowth typically occurs in infancy and can
      involve any tissue of the body. Commonly involved tissues include connective
      tissue and bone, skin, central nervous system, the eye, but it apparently can
      affect any tissue. Diagnosing of PS is difficult and the diagnostic criteria are
      controversial. Our group advocates stringent diagnostic criteria to facilitate
      research and appropriate clinical care. The benefit of strict criteria is that
      they define a clinical group that is reasonably homogenous with respect to
      manifestations and prognosis. The overgrowth of PS is progressive and can be
      difficult to manage. The progressive overgrowth most commonly causes severe
      orthopaedic complications, but it can cause many other complications. One of the
      most common complications in patients with PS is deep venous thrombosis and
      pulmonary embolism, which can cause premature death. Effective management
      requires knowledge of the wide array of manifestations and complications of the
      disorder and a team approach that includes the geneticist, surgeons, and other
      specialists.

PMID- 16883310
TI  - Assessing the potential role of photopheresis in hematopoietic stem cell
      transplant.
AB  - The First International Symposium on Photopheresis in Hematopoietic Stem Cell
      Transplantation was held in Vienna, Austria with an educational grant from
      Therakos Inc. from 25 May to 27 May 2005. Three general issues were addressed:
      (1) pathophysiology of graft-versus-host disease (GvHD), (2) induction of immune
      tolerance and the immunology of phototherapy and (3) current standard treatment
      and prevention strategies of acute and chronic GvHD and the use of extracorporeal
      photopheresis (ECP). The objectives of the meeting were to open a dialogue among
      leading researchers in photobiology, immunology, and hematopoietic stem cell
      transplantation; foster discussions and suggestions for future studies of the
      mechanism of action of ECP in acute and chronic GvHD; and promote collaboration
      between basic scientists and clinicians. As can be seen from the summaries of the
      individual presentations, important advances have been made in our understanding
      of GvHD, including the use of photoimmunology interventions and the development
      of robust model systems. It is our expectation that data from photoimmunology
      studies can be used to generate hypotheses in animal models that can further
      define the mechanism of action of ECP and help translate the findings to clinical
      trials of ECP for the prophylaxis and treatment of both chronic and acute GvHD.

PMID- 16883312
TI  - Haploidentical hematopoietic stem cell transplantation without in vitro T-cell
      depletion for the treatment of hematological malignancies.
AB  - Many patients who require allogeneic hematopoietic stem cell transplantation
      (allo-HSCT) lack a human leukocyte antigen (HLA)-matched donor. Here, we report a
      protocol for haploidentical allo-HSCT that combines granulocyte-colony
      stimulating factor primed bone marrow (G-BM) and peripheral blood stem cells
      (PBSC) without in vitro T-cell depletion (TCD). In this study, 171 patients,
      including 86 in high-risk group, underwent transplantation from haploidentical
      family donors. All patients achieved sustained, full donor chimerism. One hundred
      and eleven patients were alive in remission at a median of 682 (253-1502) days.
      The cumulative incidence of grade III-IV acute graft-versus-host disease (GVHD)
      was 23% and that of extensive chronic GVHD, 47%; these were not influenced by HLA
      disparity. Patients younger than 15 years had less grade III-IV acute GVHD than
      older patients (P=0.044). The 2-year probability of relapse was 12% for standard
      risk disease and 39% for high-risk disease. The 2-year probability of leukemia
      free survival (LFS) was 68% for standard-risk patients and 42% for high-risk
      patients (P=0.0009). Grade III-IV acute GVHD was associated with better LFS
      (P=0.0017). The results require confirmation and show that G-BM combined with
      PBSC from haploidentical family donors, without in vitro TCD, may be used as a
      good source of stem cells for allo-HSCT.

PMID- 16883313
TI  - A prompt graft-versus-thalassemia effect upon withdrawal of cyclosporine A in a
      child who received allogeneic peripheral blood stem cell transplantation.

PMID- 16883311
TI  - Low doses of GM-CSF (molgramostim) and G-CSF (filgrastim) after cyclophosphamide
      (4 g/m2) enhance the peripheral blood progenitor cell harvest: results of two
      randomized studies including 120 patients.
AB  - The use of a combination of G-CSF and GM-CSF versus G-CSF alone, after
      cyclophosphamide (4 g/m2) was compared in two randomized phase III studies,
      including 120 patients. In study A, 60 patients received 5 x 2 microg/kg/day of G
      CSF and GM-CSF compared to 5 mug/kg/day of G-CSF. In study B, 60 patients
      received 2.5 x 2 microg/kg/day G-CSF and GM-CSF compared to G-CSF alone (5
      microg/kg/day). With the aim to collect at least 5 x 10(6)/kg CD34 cells in a
      maximum of three large volume leukapherises (LK), 123 LK were performed in study
      A, showing a significantly higher number of patients reaching 10 x 10(6)/kg CD34
      cells (21/29 in G+GM-CSF arm vs 11/27 in G-CSF arm, P=0.00006). In study B, 109
      LK were performed, with similar results (10/27 vs 15/26, P=0.003). In both the
      study, the total harvest of CD34 cells/kg was twofold higher in G-CSF plus GM-CSF
      group (18.3 x 10(6) in study A and 15.85 x 10(6) in study B) than in G-CSF group
      (9 x 10(6) in study A and 8.1 x 10(6) in study B), a significant difference only
      seen in multiple myeloma, with no significant difference in terms of mobilized
      myeloma cells between G-CSF and GM-CSF groups.

PMID- 16883314
TI  - Idiopathic thrombocytopenic purpura after influenza vaccination in a bone marrow
      transplantation recipient.

PMID- 16883316
TI  - The dangers of rationing dialysis treatment: the dilemma facing a developing
      country.
AB  - The increasing burden of chronic kidney disease places enormous strains on
      resources of all countries, but especially of those with emerging economies. Few
      developing countries are able to afford dialysis programs and those that do
      ration this scarce resource. In South Africa, rationing has been practiced since
      the introduction of dialysis. Our renal unit carefully screened patients with end
      stage kidney disease (ESKD) based on certain medical and socioeconomic criteria.
      The outcome of these decisions taken by the Assessment Committee is reviewed in
      this study. Details of the 2442 patients with ESKD assessed between 1988 and 2003
      for the renal replacement program were captured. Using univariate and
      multivariate analysis, the odds of being accepted for treatment based on several
      variables were determined. The majority (52.7%) of patients with ESKD were not
      offered renal replacement therapy in the period of study. The number of kidney
      transplants progressively decreased, as did the number of patients accepted. The
      patients mostly likely to be accepted for renal replacement therapy were aged 20
      40 years, white, employed, married, non-diabetic, and lived in proximity to a
      dialysis center. Almost 60% of patients were denied renal replacement treatment
      because of social factors related to poverty. In a developing country, where
      rationing of treatment is unavoidable, it is difficult to ensure equity of
      treatment and certain groups are advantaged over others. In our experience,
      socioeconomic factors influenced decision to accept patients more profoundly than
      medical ones.

PMID- 16883317
TI  - Why don't fistulas mature?
AB  - Fistula maturation requires a compliant and responsive vasculature capable of
      dilating in response to the increased velocity of blood flowing into the newly
      created low-resistance circuit. Successful maturation to a high volume flow
      circuit capable of sustaining hemodialysis typically occurs within the first few
      weeks after creation. Failure to achieve maturation within 4-8 weeks should
      prompt a search for reversible etiologies; however, an accepted definition of
      maturation, particularly for patients not yet on dialysis remains elusive. The
      most commonly identified etiology is neointimal hyperplasia typically occurring
      in the juxta-anastomotic vein. However, failed maturation has also been reported
      secondary to impaired arterial and venous dilation and accessory veins. The exact
      frequency of each of these etiologies is unclear. Understanding the etiologies of
      impaired fistula maturation will focus future studies of targeted interventions
      to improve the rate of fistula maturation and increase the number of dialysis
      patients with a functioning autogenous fistula.

PMID- 16883318
TI  - Impaired basal NO activity in patients with glomerular disease and the influence
      of oxidative stress.
AB  - Endothelial dysfunction has been found to be linked to and predictive of
      cardiovascular events. Whether endothelial function of the renal vasculature is
      impaired in patients with chronic glomerular disease and whether oxidative stress
      is of importance in this setting has not yet been determined. In this study,
      endothelial function of the renal vasculature was investigated in 25 patients
      with chronic glomerular disease and 50 control subjects matched for age and blood
      pressure. Renal plasma flow (RPF) and glomerular filtration rate were measured by
      constant infusion input clearance technique at baseline and following infusions
      of the nitric oxide synthase (NOS) inhibitor N(G)-monomethyl-L-arginine (L-NMMA,
      4.25 mg/kg), the substrate of NOS L-arginine (100 mg/kg) and the antioxidant
      vitamin C (3 g co-infused with L-arginine 100 mg/kg). At baseline, RPF was
      similar in the two groups. The reduction in RPF in response to L-NMMA was less
      pronounced in patients with chronic glomerular disease compared to control
      subjects (-4.6+/-12 vs -9.8+/-9%; P=0.040), indicating reduced basal nitric oxide
      (NO) activity in chronic glomerular disease. Co-infusion of the antioxidant
      vitamin C on top of L-arginine induced a more pronounced increase in RPF in
      patients with chronic glomerular disease than in control subjects (21.7+/-17 vs
      10.9+/-22%; P=0.036). Our findings suggest that basal NO activity of the renal
      vasculature is reduced in patients with chronic glomerular disease compared to
      age- and blood pressure-matched control subjects. This might be in part related
      to increased oxidative stress.

PMID- 16883319
TI  - Essential roles of CFEX-mediated Cl(-)-oxalate exchange in proximal tubule NaCl
      transport and prevention of urolithiasis.
AB  - The majority of the Na(+) and Cl(-) filtered by the kidney is reabsorbed in the
      proximal tubule. In this nephron segment, a significant fraction of Cl(-) is
      transported via apical membrane Cl(-)-base exchange: Cl(-)-formate exchange, Cl(
      )-oxalate exchange, Cl(-)-OH(-) exchange, and Cl(-)-HCO(3)(-) exchange. A search
      for the transporter responsible for apical membrane Cl(-)-formate exchange in the
      proximal tubule led to the identification of CFEX (SLC26A6). Functional
      expression studies in Xenopus oocytes demonstrated that CFEX is capable of
      mediating not only Cl(-)-formate exchange but also Cl(-)-oxalate exchange, Cl(-)
      OH(-) exchange, and Cl(-)-HCO(3)(-) exchange. Studies in CFEX-null mice have
      begun to elucidate which of the anion exchange activities mediated by CFEX is
      important for renal physiology and pathophysiology in vivo. Measurements of
      transport in renal brush border vesicles isolated from CFEX-null mice
      demonstrated that CFEX primarily mediates Cl(-)-oxalate exchange rather than Cl(
      )-formate exchange. Microperfusion studies in CFEX-null mice revealed that CFEX
      plays an essential role in mediating oxalate-dependent NaCl absorption in the
      proximal tubule. CFEX-null mice were found to have hyperoxaluria and a high
      incidence of calcium oxalate urolithiasis. The etiology of hyperoxaluria in CFEX
      null mice was observed to be a defect in oxalate secretion in the intestine,
      leading to enhanced net absorption of ingested oxalate and elevation of plasma
      oxalate. Thus, by virtue of its function as a Cl(-)-oxalate exchanger, CFEX plays
      essential roles both in proximal tubule NaCl transport and in the prevention of
      hyperoxaluria and calcium oxalate nephrolithiasis.

PMID- 16883320
TI  - Osmotic nephrosis in a renal transplant recipient.

PMID- 16883321
TI  - Diagnostic relevance of pyuria in dialysis patients.

PMID- 16883322
TI  - Mesangial hypercellularity predicts antiproteinuric response to dual blockade of
      RAS in primary glomerulonephritis.
AB  - The greater antiproteinuric efficacy of converting enzyme inhibitor and
      angiotensin II receptor blocker combination (CEI+ARB), versus monotherapy with
      either drug, is not a consistent finding. We evaluated the clinicopathologic
      predictors of response to CEI+ARB in 43 patients with primary glomerulonephritis
      (GN), never treated with immunosuppressive drugs, and with persistent proteinuria
      after CEI alone. Main histological lesions were analyzed by obtaining on 557
      glomeruli and 165 arteries formal score of mesangial cellularity,
      glomerulosclerosis, tubulointerstitial damage, mononuclear cell infiltration,
      arteriosclerosis, and arteriolar hyalinosis. Duration of CEI and CEI+ARB therapy
      was similar (4.7+/-2.4 and 5.0+/-1.5 months). Proteinuria (g/day) decreased from
      3.5+/-2.9 to 2.4+/-2.3 after CEI, and to 1.5+/-1.3 after CEI+ARB (P<0.0001).
      Reduction of proteinuria after CEI+ARB was greater in proliferative versus non
      proliferative GN (-63.3+/-23.4 versus 42.4+/-23.7%, respectively; P=0.006). When
      patients were categorized in responders and non-responders to CEI+ARB, no
      difference between the two groups was detected in any demographic or clinical
      variable, whereas histology showed in responders a greater prevalence of
      proliferative GN (71.4 versus 31.8%, P=0.009) and higher score of mesangial
      cellularity (1.76+/-0.53 versus 1.20+/-0.22, P<0.0001). At multiple regression
      analysis (r(2)=0.476, P=0.001), response to CEI+ARB resulted independently
      related only to mesangial cellularity (P<0.0001). In conclusion, the best
      independent predictor of antiproteinuric efficacy of CEI+ARB in patients with
      primary GN is the degree of mesangial cellularity. This finding supports the
      experimental evidence that high angiotensin II contributes to proliferation of
      mesangial cells.

PMID- 16883323
TI  - Alterations of uromodulin biology: a common denominator of the genetically
      heterogeneous FJHN/MCKD syndrome.
AB  - Autosomal dominant hyperuricemia, gout, renal cysts, and progressive renal
      insufficiency are hallmarks of a disease complex comprising familial juvenile
      hyperuricemic nephropathy and medullary cystic kidney diseases type 1 and type 2.
      In some families the disease is associated with mutations of the gene coding for
      uromodulin, but the link between the genetic heterogeneity and mechanism(s)
      leading to the common phenotype symptoms is not clear. In 19 families, we
      investigated relevant biochemical parameters, performed linkage analysis to known
      disease loci, sequenced uromodulin gene, expressed and characterized mutant
      uromodulin proteins, and performed immunohistochemical and electronoptical
      investigation in kidney tissues. We proved genetic heterogeneity of the disease.
      Uromodulin mutations were identified in six families. Expressed, mutant proteins
      showed distinct glycosylation patterns, impaired intracellular trafficking, and
      decreased ability to be exposed on the plasma membrane, which corresponded with
      the observations in the patient's kidney tissue. We found a reduction in urinary
      uromodulin excretion as a common feature shared by almost all of the families.
      This was associated with case-specific differences in the uromodulin
      immunohistochemical staining patterns in kidney. Our results suggest that various
      genetic defects interfere with uromodulin biology, which could lead to the
      development of the common disease phenotype. 'Uromodulin-associated kidney
      diseases' may be thus a more appropriate term for this syndrome.

PMID- 16883324
TI  - Evidence of angiogenesis and microvascular regression in autosomal-dominant
      polycystic kidney disease kidneys: a corrosion cast study.
AB  - Autosomal-dominant polycystic kidney disease (ADPKD) accounts for about 10% of
      all cases of chronic renal failure requiring dialysis. The disease is
      characterized by proliferation of renal epithelial cells and formation of cysts
      that expand over years and replace the normal parenchyma of the kidney. As the
      cysts grow, the volume of the kidney can increase by more than 10-fold, implying
      that remodeling and expansion of the vasculature must occur to provide
      oxygenation and nutrition to the cyst cells. Our previous studies support the
      notion that there is angiogenesis in ADPKD. We report here results from resin
      casting of ADPKD kidneys vasculature. In this study, the corrosion-casting method
      was used in conjunction with scanning electron microscopy to study the vascular
      architecture and the evidence for angiogenesis in ADPKD kidneys. We found a well
      defined vascular network around the cysts forming a 'vascular capsule' somewhat
      similar to that described in avascular leiomyomata. We also found that the normal
      vascular architecture is lost and replaced by an assortment of capillaries of
      larger size than those in the normal kidney, mixed with flattened and spiral
      arterioles, damaged glomeruli, and atresic venules, indicative of regression of
      the microvasculature. In the same areas, there was capillary sprouting,
      considered the hallmark of angiogenesis. The present study documents regression
      changes of the vasculature and confirms the existence of angiogenesis in ADPKD
      kidneys, and suggests the use of inhibitors of angiogenesis as a possible avenue
      for the treatment of the disease.

PMID- 16883325
TI  - Protection of the kidney by thiazolidinediones: an assessment from bench to
      bedside.
AB  - The global epidemic of diabetes mellitus has led to a continuous increase in the
      prevalence of diabetic nephropathy over the past years. Thus, diabetic
      nephropathy is currently the number one cause of end-stage renal disease in the
      Western world. It represents a major public health problem for which more
      effective prevention and treatment strategies are needed. Thiazolidinediones
      (TZDs) are a class of agents that lower blood glucose through reduction of
      insulin resistance in patients with type 2 diabetes. Growing evidence support the
      concept that TZDs have several beneficial effects on the cardiovascular system
      beyond their effects on glycemic control. These benefits include: blood pressure
      lowering, triglyceride reduction, high-density lipoprotein-cholesterol elevation,
      and reduction in subclinical vascular inflammation. Moreover, data from several
      animal and human studies support the notion that TZDs reduce urine albumin
      excretion and may prevent development of renal injury. The relative lack of
      evidence, however, demonstrating the effects of TZDs on hard renal outcomes
      mandates the need for well-designed trials with this particular objective. This
      paper summarizes all the data from clinical and experimental studies relevant to
      a possible renoprotective effect of TZDs and discusses actions of these compounds
      that may contribute toward this effect.

PMID- 16883326
TI  - Safety first: messages from Digestive Disease Week 2006.

PMID- 16883327
TI  - Should we incorporate psychological care into the management of IBD?

PMID- 16883342
TI  - Is it safe to raise the age threshold for urgent endoscopy in patients with
      uncomplicated dyspepsia?

PMID- 16883343
TI  - Serum hepatitis B virus DNA level as a risk predictor for liver disease
      complications.

PMID- 16883344
TI  - Should PPIs be given to patients on antiplatelet drugs?

PMID- 16883345
TI  - How effective are 3-month and 12-month predictive models of mortality after first
      liver transplantation?

PMID- 16883346
TI  - How useful is methylglucamine diatrizoate solution in patients with small-bowel
      obstruction?

PMID- 16883347
TI  - What is the clinical benefit of portal vein embolization before extended
      hepatectomy for biliary cancer?

PMID- 16883348
TI  - Treatment options for the eradication of intestinal protozoa.
AB  - Pathogenic intestinal protozoa are responsible for clinically important
      infections in both the developed and the developing world. These organisms are
      responsible for both acute and chronic diarrhea, and Entamoeba histolytica, which
      affects the colon, can spread to involve the liver. Many of these pathogens,
      particularly the intracellular protozoa that predominantly affect the small
      intestine, produce their most devastating effects in patients with HIV/AIDS and
      other forms of immune deficiency. There are also various intestinal protozoa that
      do not seem to have any adverse effects on humans and can, therefore, be regarded
      as harmless commensal organisms. Although treatment has been available for
      several decades for giardiasis, isosporiasis and amoebiasis, until recently there
      have been no effective remedies for infection with intestinal coccidia-
      Cryptosporidium, Microsporidium and Cyclospora species. Cyclospora respond well
      to co-trimoxazole, microsporidia respond variably to albendazole, and
      cryptosporidia can often be eradicated by nitazoxanide. In chronically infected
      HIV-positive patients, treatment with multidrug regimens usually results in rapid
      resolution of the diarrhea and, in many instances, eradication of the parasite.

PMID- 16883349
TI  - Treatment of chronic hepatitis B.
AB  - Treatment of chronic hepatitis B has improved substantially over the past five
      years. Pegylated interferon alpha2a and entecavir have been approved by the FDA
      and joined the armamentarium of therapies that includes inteferon alpha (IFN
      alpha), lamivudine, and adefovir dipivoxil. Several key questions come to mind
      regarding treatment. Who should receive treatment? Which agent should they be
      given? How long should treatment last? Treatment is indicated for patients with a
      high pretreatment alanine aminotransferase level, detectable HBV DNA, and active
      inflammation on liver biopsy. When selecting an agent, the likelihood of
      achieving a sustained response should be weighed against long-term risks. IFN
      alpha, lamivudine, and adefovir dipivoxil are equally efficacious; however, even
      though IFN-alpha and pegylated IFN-alpha have a durable response, both are
      associated with unpleasant side effects. Long-term lamivudine therapy has a high
      rate of drug resistance compared with adefovir dipivoxil, which has a low rate of
      drug resistance and a small risk of reversible nephrotoxicity. Entecavir reduces
      HBV load more effectively than the other therapies, but it is associated with
      increased drug resistance in patients with lamivudine-resistant HBV. The key to
      therapy seems to be some combination of therapies--both existing and those in
      development--that has yet to be determined.

PMID- 16883350
TI  - Technology insight: Photodynamic therapy for cholangiocarcinoma.
AB  - Cholangiocarcinoma is, in most cases, rapidly fatal. Curative resection can only
      be offered to approximately 10% of patients. Even after seemingly curative
      resection, recurrence frequently occurs. Adjuvant chemotherapy and/or
      radiotherapy do not reduce the recurrence rate after resection. In the palliative
      setting, endoscopic or percutaneous biliary drainage is performed to relieve
      jaundice; however, poor results have been obtained in patients with tumors
      involving the intrahepatic bile ducts. Biliary drainage alleviates jaundice, but
      there is no evidence that it prolongs life. Palliative chemotherapy and/or
      radiotherapy have not been proven to prolong life and relieve jaundice.
      Photodynamic therapy (PDT) is a relatively new local, minimally invasive
      procedure that can be used to treat cholangiocarcinoma. PDT uses the physical
      properties of light-absorbing molecules, so-called photosensitizers, which
      accumulate within proliferating cells. Activation of the photosensitizer by a non
      thermal laser leads to selective photochemical destruction of tumors. In a
      randomized trial of patients with nonresectable cholangiocarcinoma, PDT prolonged
      survival time, improved cholestasis and quality of life considerably, and had a
      favorable side-effect profile. A second randomized trial confirmed the beneficial
      effect of PDT. For the time being, PDT is recommended for patients with
      nonresectable disease. The role of PDT before and after surgical resection needs
      to be assessed.

PMID- 16883351
TI  - A patient with abdominal pain and markedly elevated transaminase levels after
      cholecystectomy.
AB  - BACKGROUND: A 33-year-old white female with a history of cholecystectomy
      presented to the emergency department with intermittent severe abdominal pain
      radiating from the left upper quadrant to the right upper quadrant, associated
      with nausea and emesis. Three weeks previously the patient had presented to the
      emergency department with similar pain in the abdomen. Laboratory investigations
      had revealed elevated bilirubin, transaminase, and alkaline phosphatase levels.
      At that time, pain and liver chemistry test results improved and the patient was
      discharged on hospital day 3. She denied a history of alcohol use, new
      medications, or the ingestion of other toxins. INVESTIGATIONS: History and
      physical examination, liver chemistry tests, viral hepatitis serology tests,
      autoimmune serology tests, abdominal ultrasound, liver biopsy, and an endoscopic
      retrograde cholangiopancreatogram. DIAGNOSIS: Choledocholithiasis. MANAGEMENT:
      Endoscopic retrograde cholangiopancreatogram with sphincterotomy, removal of an 8
      mm distal common bile duct stone, and pancreatic stent placement.

PMID- 16883352
TI  - Stroke-evoked angiogenesis results in a transient population of microvessels.
AB  - The role of angiogenesis after stroke is unclear; if angiogenesis supports long
      term recovery of blood flow, then microvessel hyperdensity consequent to
      angiogenesis should persist in infarcted cortex. Here, we assess the long-term
      stability of ischemia-induced microvessels after 2-h transient rat middle
      cerebral artery occlusion (tMCAo) followed by 30, 90, or 165 days of reperfusion.
      Stereological measures of microvessel density were taken adjacent to and within
      cortical cysts. Vascular permeability was documented by extravasation of
      immunoglobulin (IgG) and of fluorescein-dextran. After 30 days reperfusion, a
      significantly increased microvessel volume density (V(V)) was restricted to the
      inner margin of cystic infarcts as compared with the region external to the
      infarct or contralateral control cortex (F=42.675, P<0.001). The hyperdense
      ischemic vasculature was abnormally leaky to IgG and fluorescein-dextran. Between
      30 and 90 days of reperfusion, this vessel hyperdensity regressed significantly
      and then regressed further but less drastically between 90 and 165 days.
      Phagocytic macrophages were restricted to the infarct and dynamic changes in
      their number correlated with microvessel regression. Additional ED-1 labeled
      inflammatory cells were widely distributed inside and external to the infarct,
      even after 165 days of reperfusion. These data show that ischemia evoked
      angiogenesis results, at least in part, in transient populations of leaky
      microvessels and phagocytic macrophages. This suggests that a major role of this
      angiogenesis is for the removal of necrotic brain tissue.

PMID- 16883353
TI  - Functional uncoupling of hemodynamic from neuronal response by inhibition of
      neuronal nitric oxide synthase.
AB  - The cerebrovascular coupling under neuronal nitric oxide synthase (nNOS)
      inhibition was investigated in alpha-chloralose anesthetized rats. Cerebral blood
      flow (CBF), cerebral blood volume (CBV), and blood oxygenation level dependent
      (BOLD) responses to electrical stimulation of the forepaw were measured before
      and after an intraperitoneal bolus of 7-nitroindazole (7-NI), an in vivo
      inhibitor of the neuronal isoform of nitric oxide synthase. Neuronal activity was
      measured by recording somatosensory-evoked potentials (SEPs) via intracranial
      electrodes. 7-Nitroindazole produced a significant attenuation of the activation
      elicited CBF (P<10(-6)), CBV (P<10(-6)), and BOLD responses (P<10(-6)), without
      affecting the baseline perfusion level. The average DeltaCBF was nulled, while
      DeltaBOLD and DeltaCBV decreased to approximately 30% of their respective
      amplitudes before 7-NI administration. The average SEP amplitude decreased (P<10(
      5)) to approximately 60% of its pretreatment value. These data describe a
      pharmacologically induced uncoupling between neuronal and hemodynamic responses
      to functional activation, and provide further support for the critical role of
      neuronally produced NO in the cerebrovascular coupling.

PMID- 16883355
TI  - Form follows function: the architecture of complex networks.

PMID- 16883354
TI  - Noise in transcription negative feedback loops: simulation and experimental
      analysis.
AB  - Negative feedback loops have been invoked as a way to control and decrease
      transcriptional noise. Here, we have built three circuits to test the effect of
      negative feedback loops on transcriptional noise of an autoregulated gene
      encoding a transcription factor (TF) and a downstream gene (DG), regulated by
      this TF. Experimental analysis shows that self-repression decreases noise
      compared to expression from a non-regulated promoter. Interestingly enough, we
      find that noise minimization by negative feedback loop is optimal within a range
      of repression strength. Repression values outside this range result in noise
      increase producing a U-shaped behaviour. This behaviour is the result of external
      noise probably arising from plasmid fluctuations as shown by simulation of the
      network. Regarding the target gene of a self-repressed TF (sTF), we find a strong
      decrease of noise when repression by the sTF is strong and a higher degree of
      noise anti-correlation between sTF and its target. Simulations of the circuits
      indicate that the main source of noise in these circuits could come from plasmid
      variation and therefore that negative feedback loops play an important role in
      suppressing both external and internal noise. An important observation is that DG
      expression without negative feedback exhibits bimodality at intermediate TF
      repression values. This bimodal behaviour seems to be the result of external
      noise as it can only be found in those simulations that include plasmid
      variation.

PMID- 16883356
TI  - Economics of selective laser trabeculoplasty as primary therapy for glaucoma.

PMID- 16883357
TI  - Integrated vision care in Nova Scotia: a Canadian model?

PMID- 16883358
TI  - How can we strengthen ophthalmic research in Africa?

PMID- 16883360
TI  - Projected cost comparison of selective laser trabeculoplasty versus glaucoma
      medication in the Ontario Health Insurance Plan.
AB  - BACKGROUND: The projected 6-year cost comparison of primary selective laser
      trabeculoplasty (SLT) versus primary medical therapy in the treatment of open
      angle glaucoma for Ontario patients aged 65 years or more is presented. Costs are
      taken from the perspective of the Ontario Health Insurance Plan at a per-patient
      level. METHODS: The cost of each medication was obtained from the 2003 Ontario
      Drug Benefits formulary. The average annual cost of medications was determined by
      estimating the provincial prescription rate of glaucoma medications, with
      reference to both a volume-per-bottle study of these drugs and a study of
      pharmacy claims reports. A representative provincial prescription rate was
      calculated by reviewing 707 patient charts selected randomly from 5
      ophthalmologic practices across Ontario. Medication therapies were categorized
      into mono-, bi-, and tri-drug therapy groups. The cost of SLT was analyzed under
      the following 2 scenarios. SLT rep 2y assumed a duration of 2 years before repeat
      SLT was necessary. SLT rep 3y assumed a duration of 3 years before repeat SLT was
      necessary. Bilateral 180 degrees SLT treatment and repeatability of SLT was
      assumed. The cost of surgery for patients who fail SLT or medical therapy was not
      accounted for in this study nor was the cost of patients who required medical
      therapy in conjunction with SLT. RESULTS: In the SLT rep 2y scenario, the use of
      primary SLT over mono-, bi-, and tri-drug therapy produced a 6-year cumulative
      cost savings of 206.54 dollars, 1668.64 dollars, and 2992.67 dollars per patient,
      respectively. In the SLT rep 3y scenario, the use of primary SLT over mono-, bi-,
      and tri-drug therapy produced a 6-year cumulative cost savings of 580.52 dollars,
      2042.82 dollars, and 3366.65 dollars per patient, respectively. INTERPRETATION:
      Our findings suggest that SLT as primary therapy, at a per-patient level, offers
      a modest potential cost saving over primary medical therapy in the management of
      open-angle glaucoma for Ontario patients aged 65 years or more.

PMID- 16883361
TI  - Review of consecutive phacotrabeculectomies supplemented with early needle
      revision and antimetabolites.
AB  - BACKGROUND: To describe the results of a novel postoperative management approach
      for patients undergoing combined cataract and glaucoma surgery supplemented with
      early needle revision and antimetabolites. METHODS: Consecutive retrospective
      chart review identified 66 patients who had undergone combined cataract and
      glaucoma surgery with early needling and antimetabolite injections between
      January 2002 and May 2003; 8 patients were excluded from analysis because of
      missing data or inadequate follow-up time. Single-site phacotrabeculectomy was
      performed followed by subconjunctival antimetabolite injections of 5-fluorouracil
      (5-FU). Needling was performed as an office procedure if early evidence of
      subconjunctival scarring was observed 2-6 weeks after surgery. Additional
      subconjunctival 5-FU injections were administered after needling, and repeat
      needling was performed with 5-FU or mitomycin-C if subconjunctival scarring
      recurred. A complete success was defined as a reduction in intraocular pressure
      (IOP) to <18 mm Hg without the use of antiglaucoma medications or further
      surgical procedures to control IOP. The outcome was considered a qualified
      success when antiglaucoma medications were required to achieve the same result.
      RESULTS: The mean preoperative IOP was 21.9 (SD 6.3) mm Hg, and the mean
      postoperative IOP at 6 months was 13.0 (SD 6.7) mm Hg. The mean number of
      medications was reduced from 2.9 (SD 1.3) preoperatively to 0.5 (SD 0.9)
      postoperatively at 6 months. Needling was performed because of early evidence of
      subconjunctival scarring in 34 patients. The 6-month outcomes of 37 patients
      (64%) were a complete success and of 47 patients (81%) were a complete or
      qualified success. A longer follow-up of 10-23 months was attained in 25 of the
      58 patients. At latest visit, the mean postoperative IOP of this group was 13.0
      (SD 5.5) mm Hg, the mean number of postoperative medications was 0.7 (SD 1), and
      21 of the 25 (84%) had achieved a complete or qualified success. The most common
      complication for all 58 patients was an early, self-limited postoperative wound
      leak that was unrelated to the needling intervention and was observed in 26
      patients (45%). INTERPRETATION: Phacotrabeculectomy supplemented with early
      needle revision and antimetabolites may improve outcomes of combined cataract and
      glaucoma surgery.

PMID- 16883362
TI  - Long-term refractive change after intraocular lens implantation in childhood.
AB  - BACKGROUND: To determine refractive change occurring with age in children who had
      cataract removal with intraocular lens implantation and in whom the immediate
      postoperative refraction was targeted either to match the refractive error of the
      opposite eye in unilateral cases, or for only a small refractive error when
      surgery was bilateral. METHODS: Retrospective review of the refractive error over
      time in 36 eyes of 25 children who underwent cataract removal (11 bilateral) with
      insertion of an intraocular lens from 1987 to 1998 and who had at least 4 years
      follow-up, but no glaucoma. RESULTS: Mean age at surgery was 5.5 years (median
      5.7 y, range 1.3-12 y), with a mean follow-up of 8 years (median 6 y, range 4-16
      y). The average refraction followed a logarithmic decline with age. Although eyes
      with unilateral surgery had a slightly faster rate of change and lower final
      refraction than did eyes with bilateral surgery, this difference was not
      statistically significant. Variation from this trend was also observed in 3
      patients. When the hyperopic refractive error created immediately after surgery
      was small, children usually became significantly myopic when older, often
      creating anisometropic myopia in unilateral cases. INTERPRETATION: When
      implanting intraocular lenses bilaterally one should aim for a significant but
      balanced hyperopic correction immediately postoperatively in young patients,
      anticipating that there will be emmetropization with aging. Parents should be
      warned that variations can occur.

PMID- 16883363
TI  - Pupillography of relative afferent pupillary defect contralateral to monocular
      mature cataract.
AB  - CASE REPORT: Few previous reports have documented a relative afferent pupillary
      defect (RAPD) in the eye contralateral to a dense unilateral cataract. We report
      pupillographic findings of a 55-year-old man with a mature cataract in the left
      eye and an RAPD in the right eye, whose RAPD disappeared after cataract surgery
      in his left eye. Using binocular infrared video pupillography, we recorded the
      pupillary responses of the two eyes simultaneously during an automated swinging
      flashlight test before and after the cataract surgery. The average contraction
      amplitude in both eyes was significantly larger when the unaffected left eye was
      stimulated before the cataract surgery, but this difference in contraction
      amplitude disappeared after surgery on the left eye. COMMENTS: An RAPD was shown
      quantitatively with a pupillographic technique in the eye contralateral to a
      mature cataract, confirming previous studies that indicate a dense cataract may
      produce a small but definite RAPD in the contralateral eye. Such an RAPD
      associated with a dense cataract must be taken into consideration when evaluating
      patients with unilateral visual loss.

PMID- 16883364
TI  - Apoptosis in perforated cornea of a patient with graft-versus-host disease.
AB  - CASE REPORT: Although ocular complications associated with graft-versus-host
      disease (GVHD) can include corneal dysfunction, corneal perforation is not
      common. We report the presence of apoptotic cells in a perforated cornea of a
      patient with GVHD. A 72-year-old man with the angioimmunoblastic type of
      malignant lymphoma developed chronic GVHD after allogeneic peripheral blood stem
      cell transplantation. Despite systemic and topical treatment, both corneas
      perforated, and penetrating keratoplasty with cataract extraction and intraocular
      lens implantation was performed on both eyes. COMMENTS: The corneal button
      excised from the right eye was examined histologically and stained for apoptotic
      cells by TdT-mediated dUTP nick end labeling (TUNEL). This revealed thinning of
      the epithelial cell layer and stroma, with cells, including lymphocytes,
      infiltrating to the site of the perforation. Some of the epithelial cells and
      keratocytes were TUNEL positive. The presence of apoptotic cells in our case
      suggests that apoptosis may be involved in the perforation of the cornea in
      patients with GVHD.

PMID- 16883365
TI  - Intraoperative eye position after sub-Tenon's anesthesia for cataract surgery.
AB  - BACKGROUND: To evaluate the incidence and extent of ocular deviation associated
      with sub-Tenon's anesthesia. METHODS: Seventy-five consecutive patients
      undergoing routine phacoemulsification with sub-Tenon's anesthesia at the Eye
      Unit, Royal Gwent Hospital, were prospectively enrolled in this observational
      case series. The exclusion criteria were patients taking warfarin, or patients
      with preexisting ocular motility disorders, allergy to local anesthetics, or
      previous surgery for squint or retinal detachment. Eleven patients were
      subsequently excluded from the study group as they required additional anesthesia
      blocks before measurements were taken for ocular deviation. We injected 5 mL of a
      local anesthetic mixture of 2% lignocaine and 7.5 mg/mL levobupivacaine in the
      sub-Tenon's space in the inferonasal quadrant. Ocular deviation was assessed
      objectively by means of the Krimsky test. Forced duction tests were performed
      before and after anesthesia. RESULTS: Hyperdeviation was documented in 49 (77%)
      eyes, exodeviation in 62 (97%), and hypodeviation in 6 (9.4%). No esodeviations
      were documented. Only 2 patients were orthophoric after anesthesia. Mean vertical
      deviation was 4.4 prism dioptres (PD) (SD 4.7 PD, 95% CI 3.2-5.5 PD, range 0-14
      PD). Mean horizontal deviation was 19.5 (SD 9.6, 95% CI 17-22, range 0-50) PD.
      Forced duction test revealed no mechanical restriction before or after
      anesthesia. INTERPRETATION: This study suggests that there is an appreciable
      ocular deviation with sub-Tenon's anesthesia. Intraoperative ocular deviation may
      make certain procedures more difficult; therefore, we recommend a low threshold
      for an additional corrective block administered before surgery to rectify the
      deviation.

PMID- 16883366
TI  - The evidence for efficacy of omega-3 fatty acids in preventing or slowing the
      progression of retinitis pigmentosa: a systematic review.
AB  - BACKGROUND: Studies in preterm and term human infants have suggested that a
      dietary supply of omega-3 fatty acids is essential for optimal visual
      development. Several basic science studies support the hypothesis that omega-3
      fatty acids may be useful therapeutic agents for pathologies of the retina and
      lens. As part of a systematic review of the effect of omega-3 fatty acids on eye
      health, the purpose of this study was to conduct a systematic review of the
      scientific-medical literature to appraise and synthesize the evidence for the
      effects of omega-3 fatty acids in preventing the development or progression of
      retinitis pigmentosa. METHODS: A comprehensive search was undertaken in MEDLINE,
      PREMEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Global
      Health, and Dissertation Abstracts. Unpublished literature was sought through
      manual searches of reference lists of included studies and key review articles
      and from the files of content experts. Searches were not restricted by language
      of publication, publication type, or study design. Eligibility criteria were
      applied to screen eligible studies on two levels. Data extraction and quality
      assessment were performed. RESULTS: Six studies published between 1995 and 2004
      met eligibility criteria in investigating the question of the possible value of
      omega-3 fatty acids in slowing the progression of retinitis pigmentosa. Meta
      analysis was not performed because there was not enough available information for
      formal quantitative analysis. INTERPRETATION: There are trends in improvement of
      some retinitis pigmentosa outcomes with omega-3 fatty acids in the higher quality
      studies. Clinical research is preliminary in this field, however. Accordingly,
      definitive answers will require significantly more observational and
      interventional clinical research.

PMID- 16883367
TI  - Valsalva retinopathy associated with fiberoptic gastroenteroscopy.
AB  - CASE REPORT: A 45-year-old woman presented with a sudden loss of vision in her
      left eye, which occurred while she was having a routine upper fiberoptic
      gastroenteroscopy. According to the gastrointestinal specialist, the patient had
      performed multiple sustained Valsalva maneuvers during the procedure. Funduscopy
      showed a preretinal hemorrhage with a half disc diameter in the fovea of the left
      eye. COMMENTS: A diagnosis of Valsalva retinopathy was made on the basis of
      history and fundus finding. The hemorrhage resolved within 2 months without any
      sequelae. To our knowledge, this is the first report of the occurrence of
      Valsalva retinopathy following a routine upper fiberoptic gastroenteroscopy.

PMID- 16883368
TI  - Bilateral exudative retinal detachments as initial presentation of sympathetic
      ophthalmia in Turner syndrome.
AB  - CASE REPORT: Sympathetic ophthalmia typically presents as bilateral granulomatous
      panuveitis that occurs after penetrating ocular injury. We describe a case of
      bilateral exudative retinal detachments in a patient with Turner syndrome and
      sympathetic ophthalmia. COMMENTS: To our knowledge, this is the first report of
      sympathetic ophthalmia in Turner syndrome.

PMID- 16883369
TI  - Intermittent reversal of complete ptosis associated with sphenoid wing
      meningiomas.
AB  - CASE REPORT: Ptosis secondary to dense oculomotor pareses generally improves over
      several months, but intermittent elevation of the eyelid has not been reported.
      The authors describe two patients who demonstrated intermittent involuntary
      monocular eyelid elevation in an eye with complete ptosis caused by partial
      resection of sphenoid wing meningioma. Both patients had complete ophthalmoplegia
      and decreased corneal sensation. The involved eye was ipsilateral to a meningioma
      that had been debulked 11 to 12 months previously. Although the lids were devoid
      of volitional movement, each patient could elevate the lid for 10 to 20 seconds
      by either tickling the eyelashes or rubbing the eyelids. The lids occasionally
      rose spontaneously and there was no clinical evidence of aberrant regeneration or
      cyclic spasm. COMMENTS: Although the mechanism of action of this involuntary
      eyelid elevation is unknown, it is possible that some process of aberrant
      regeneration activated by sensory stimuli is responsible.

PMID- 16883370
TI  - Quantitative analysis of temporal artery contraction after biopsy for evaluation
      of giant cell arteritis.
AB  - BACKGROUND: Although the degree of contraction of temporal artery biopsy
      specimens after formalin fixation has been previously reported to range from 6%
      to 13%, the degree of contraction before fixation has not been previously
      studied. The aim of this study was to quantify the postexcision (prefixation)
      contraction of temporal artery biopsy specimens and to determine the relationship
      between contraction and the result of the biopsy. METHODS: All patients
      undergoing temporal artery biopsies from February 2003 through May 2004 were
      retrospectively reviewed. Contraction was determined by subtracting the in vivo
      and ex vivo lengths, then dividing the difference by the in vivo length to obtain
      a percentage of contraction. Statistical analysis was performed with the unpaired
      t test and Fisher exact test. RESULTS: We reviewed 37 negative and 7 positive
      biopsies for giant cell arteritis (GCA). For specimens positive for GCA, the mean
      contraction was 12%, whereas for negative specimens, mean contraction was 22%.
      There was a significant difference in the contraction between the specimens
      positive and negative for GCA (p = 0.009). The Fisher exact test revealed that
      GCA was positively associated with arterial contraction of less than 15% (p =
      0.002). INTERPRETATION: The temporal artery can contract substantially after
      excision and before tissue fixation. GCA-positive specimens exhibit statistically
      less contractility than negative specimens.

PMID- 16883371
TI  - Intracranial foreign body in a globe-perforating injury.
AB  - CASE REPORT: To report a case with an intracranial foreign body in the setting of
      a globe-perforating injury. A 53-year-old man experienced a sudden pain in his
      right eye while he was breaking a stone with a sledgehammer. Upon examination, a
      1.5 mm superomedial corneoscleral perforation site was noted. Cranial sections of
      axial orbital computed tomography (CT) revealed a foreign body at the middle
      cranial fossa. COMMENTS: A high index of suspicion is required to detect an
      intracranial foreign body in ocular injuries. Orbital CT must be included in
      preoperative evaluation of these patients and cranial sections must also be
      examined carefully.

PMID- 16883373
TI  - Are diagnostic lumbar medial branch blocks valid? Results of 2-year follow-up.
AB  - The precise cause of low back pain based on clinical history, physical
      examination, radiological imaging, and electrophysiological testing can be
      identified in only 15% of patients in the absence of disc herniation and
      neurological deficit. The prevalence of chronic lumbar zygapophysial (facet)
      joint pain ranges from 15% to 45% utilizing comparative local anesthetic blocks
      in controlled settings in accordance with the criteria established by the
      International Association for the Study of Pain. Currently, facet joint injection
      procedures are considered as the gold standard in the diagnosis of facet joint
      pain. Facet blocks have been criticized as lacking diagnostic validity, along
      with other tests, including discography, neurophysiologic tests, stress
      radiographs, x-ray studies, bone scintigraphy, thermography and diagnostic
      ultrasound. However, these assumptions have been based on biased evaluations
      without consideration of the criteria of the International Association for the
      Study of Pain, as well as the nature of controlled diagnostic blocks. Utilizing
      the criteria established by the Agency for Healthcare Research and Quality (AHRQ)
      for Systems to Rate the Strength of Scientific Evidence, it was shown that the
      validity, specificity, and sensitivity of facet joint nerve blocks are considered
      strong in the diagnosis of facet joint pain. The accuracy of a diagnostic test is
      best determined by comparing it to an appropriate reference standard, such as
      biopsy, surgery, autopsy or long-term follow-up. Since we are unable to apply
      reference standards of biopsy, surgery, or autopsy, and pain relief has been
      argued as an inconsistent feature, long-term follow-up has been considered as the
      best indicator. This study was undertaken to evaluate stability of the diagnosis
      of lumbar facet joint pain following comparative local anesthetic blocks at a
      follow-up after 2 years. The results showed that 85% of the patients available
      for follow-up withstood the diagnosis of facet joint pain at the end of 2 years,
      whereas this proportion decreased to 75%, if all the patients in the study were
      included in the analysis.

PMID- 16883374
TI  - Is fluoroscopy necessary for sacroiliac joint injections?
AB  - The use of sacroiliac joint injection has been a steadily increasing for
      therapeutic and diagnostic purposes in the United States. Because of the
      conceivably easy accessibility of sacroiliac joint and reported low incidence of
      morbidity, the sacroiliac joint injection is felt to be a procedure that maybe
      performed easily in the office based setting. While this procedure may be common,
      the sacroiliac joint injection is not performed accurately without the aide of
      imaging. Further complicating the issue of sacroiliac joint injections is the
      lack of specific and reliable diagnostic testing. Clinical evaluation and imaging
      studies are often unreliable and practitioners often mistakenly assume that pain
      over the posterior superior iliac spine is pathognomonic for sacral joint pain.
      In addition, referral patterns are unreliable and bedside testing is often non
      diagnostic. Sixty patients undergoing sacroiliac joint injections were studied.
      Sacroiliac joint injections were placed blindly then examined under fluoroscopy
      for accurate needle placement. The needle was placed by a single this experienced
      spinal injectionist. Results of blind needle placement revealed that only 5 of 60
      patients were felt to have needle placement approximating a therapeutic point of
      contact with the sacroiliac joint. Furthermore, the posterior superior iliac
      spine, was found to be a poor indicator of sacroiliac joint anatomic access. The
      results of this study show that accurate placement of sacroiliac joint injections
      is successful without fluoroscopy in only 12% of the patients, even in
      experienced hands.

PMID- 16883375
TI  - Correlates of non-physiological behavior in patients with chronic low back pain.
AB  - It is widely believed that the extent of a patient's subjective complaints are
      often based on developmental, psychological, social, and cultural factors rather
      than structural or physical pathology. In patients presenting with chronic low
      back pain, underlying behavioral problems may not be immediately apparent. These
      behavioral or non-physiological issues may be secondary to a deliberate deception
      or may be associated with psychological distress. Waddell et al developed a
      standardized assessment of behavioral or non-organic signs and symptoms in hopes
      that such an evaluation of the patient could lead to better utilization of
      surgical and diagnostic procedures. Multiple authors have described varying
      results correlating excessive pain behavior with psychological disorders. This
      study was designed to evaluate psychological correlates of pain behavior in 120
      chronic low back pain patients in an interventional pain management setting with
      60 men and 60 women. Patients were evaluated with completion of a physical
      examination, which included Waddell's non-physiological symptoms and signs, and
      psychological evaluation by Pain Patient Profile (P-3). Results showed that 27
      patients (22%) presented with non-physiological symptoms, 34 patients (28%) with
      non-physiological signs, and 19 patients (16%) with combined presence of non
      physiological signs and symptoms. Overall there was significant correlation of
      non-physiological signs with depression, anxiety, and somatization, both by
      diagnosis of depression, diagnosis of anxiety and elevated scores. However,
      correlation was present for non-physiological symptoms only with elevated scores
      of anxiety and somatization.

PMID- 16883376
TI  - Are fluoroscopic caudal epidural steroid injections effective for managing
      chronic low back pain?
AB  - OBJECTIVE: This study sought to determine the efficacy of fluoroscopic caudal
      epidural steroid injections as a conservative treatment in patients with
      presumably chronic lumbar discogenic pain. SUMMARY OF BACKGROUND DATA: Epidural
      steroid injections have been used in the treatment of lumbar radicular pain with
      success. However, despite their widespread use, there are few, if any, reports of
      the efficacy of Epidural steroid injections in patients with predominantly axial
      lumbar pain. Prior studies have been limited by the use of non-fluoroscopically
      guided injections and failing to apply a specific injection approach (i.e.
      transforaminal, interlaminar, or caudal) to a specific patient population.
      METHODS: Ninety-seven patients with chronic axial low back pain and Magnetic
      Resonance Imaging evidence of disc pathology without stenosis were selected from
      chart review. All patients received at least one fluoroscopically guided caudal
      epidural injection with 12 mg of betamethasone and 8 cc of 0.5% lidocaine.
      Collected follow-up information included Roland-Morris Disability, Visual Numeric
      Pain Scale, and patient satisfaction scores. RESULTS: Only nineteen patients
      (23%) were determined to have a successful long- term (> 1 year) outcome and 65
      (77%) were deemed failures. Average follow-up was 28.6 +/- 15.6 months. Successes
      were found to differ significantly from failures in pre-injection pain scores and
      patient satisfaction. Overall patient satisfaction was 45%. CONCLUSION: At
      greater than two year follow-up, the efficacy of fluoroscopically guided caudal
      epidural steroid injections in patients with chronic lumbar discogenic pain is
      poor. Patient satisfaction exceeds the reported rate of efficacy. Patients
      responding to injection have significantly lower pre-injection pain scores.

PMID- 16883377
TI  - Prevalence of illicit drug use in patients without controlled substance abuse in
      interventional pain management.
AB  - Drug abuse with illicit drugs and licit drugs has been increasing steadily over
      the past decade. A recent National Household Survey on Drug Abuse found
      statistically significant increases between 2000 and 2001 in the use of multiple
      drugs, including marijuana, cocaine, and non-medical use of pain relievers and
      tranquilizers. Prescription controlled substance abuse is a major issue in
      chronic pain management. Various means suggested to avoid or monitor abuse in
      patients in treatment include urine/serum drug screening whenever requested,
      along with other precautions including one prescribing physician and one
      designated pharmacy, etc. Based on the present evidence, physicians assume that
      patients adhering to controlled substance agreements and without obvious
      dependency behavior do not abuse either illicit or licit drugs. Thus, it is
      accepted that there is no necessity to perform routine urine/drug testing in this
      specific group of the patient population. One hundred patients undergoing
      interventional pain management and receiving controlled substances were randomly
      selected for evaluation of illicit drug abuse by urine drug testing. They were
      selected from a total of 250 patients who were identified as non-abusers of
      prescription drugs. Results showed that illicit drug abuse in patients without
      history of controlled substance abuse was seen in 16 patients. Thirteen of the 16
      patients tested positive for marijuana and 3 patients tested positive for
      cocaine. Only one patient tested positive for a combined use of both marijuana
      and cocaine. This study showed that, in an interventional pain management
      setting, there is significant use of illicit drugs (16%) with 13% use of
      marijuana and 3% use of cocaine in patients who are considered as non-abusers of
      prescription controlled substances and those who are adherent to controlled
      substance agreements. However, if cocaine is considered as a hardcore drug in
      contrast to marijuana, abuse of hardcore illicit drugs is only 3%.

PMID- 16883378
TI  - Sacroiliac joint pain and dysfunction.
AB  - The purpose of this current opinion on sacroiliac joint pain and dysfunction is
      to assist interventional pain physicians to apply appropriate treatment decisions
      and rationale to their patients in pain. Discussion of relevant scientific data
      and controversial positions will be provided. This review is intended to help
      characterize the sacroiliac joint as a pain generator, and explore its
      contribution to the differential diagnosis of low back pain. Historical,
      technical, and current treatment practice will be characterized against current
      evidence. Discussion will provoke support or criticism of the relevant scientific
      data, and general recommendations for interventional pain management physicians
      should be considered within the context of the individual practitioners skill and
      practice patterns. Current Opinion is not intended to provide a standard of care.

PMID- 16883379
TI  - Supraclavicular approach to brachial plexus block using fluoroscopic anatomic
      landmarks and nerve stimulation.
AB  - Irritation of neural structures, specifically the brachial plexus outside of the
      cervical spine is capable of producing pain in the upper extremity. These pain
      patterns may be similar to pain originating from the cervical spine, presenting a
      diagnostic challenge. Brachial plexus block is performed at multiple levels,
      including interscalene, supraclavicular, infraclavicular, and axillary.
      Interscalene block is frequently utilized by interventional pain management
      physicians for diagnostic and therapeutic purposes to isolate and manage the
      brachial plexus as a pain generator. The traditional methods employed in
      performing interscalene or supraclavicular brachial plexus blocks are associated
      with multiple disadvantages. A new technique is described to meet five essential
      requirements encompassing safety, specificity, consistency, reproducibility and a
      high success rate. Relevant anatomy and proposed technique of brachial plexus
      block is described. The procedure is performed under fluoroscopy with contrast
      injection. It is concluded that the proposed technique of brachial plexus block
      is useful for brachial plexus blockade providing precision and specificity with
      minimal complications.

PMID- 16883380
TI  - A historical review and current perspective on the intervertebral disc
      prosthesis.
AB  - Spinal fusion for degenerative disc disease has been associated with a variety of
      side effects, including increased morbidity, infection, failed back syndrome,
      pseudoarthrosis, and acceleration of degenerative changes in adjacent
      intervertebral discs and facet joints. Based on the experience of arthroplasty of
      hip and other joints, there has been an escalating in research emphasizing the
      design and development of an artificial disc prosthesis. However, these
      artificial discs have not been very successful when compared with hip or knee
      replacements. Based on clinical and anatomical data, multiple authors have
      postulated that the degenerative process of intervertebral disc evolves through
      three stages; dysfunction, instability and stabilization, with relatively
      distinct clinical and radiological findings. Even though magnetic resonance
      imaging is considered as the primary diagnostic tool for degenerative disease, it
      is unable to reliably ascertain which disc level is responsible for generating
      axial pain symptoms. Consequently, discography is the most precise test to
      localize the level of pathology. Multiple design criteria have been proposed for
      an ideal intervertebral prosthesis which included endurance, materials behavior,
      geometry, kinematics, dynamics, motion constraints, fixation to bones and safety.
      The development of artificial disc technology has culminated into two types of
      disc replacements, namely total disc replacement and a nucleus pulposus
      replacement. In addition, four prosthetic models have been proposed which include
      hydraulic, elastic, composite, and mechanical. Clinical outcomes of total disc
      replacement and nucleus replacement have been variable. This review describes
      natural history of disc disease and the diagnostic process, anatomical and
      biomechanical considerations, design criteria for an ideal intervertebral
      prosthesis, evolution of artificial disc prosthesis, clinical outcomes of the
      total disc and nucleus replacement, and prospects and meridians for future
      research.

PMID- 16883381
TI  - Provocative tests in cervical spine examination: historical basis and scientific
      analyses.
AB  - The majority of the provocative tests described for physical examination of the
      neck and cervical spine relate to identification of radiculopathy, spinal cord,
      or brachial plexus pathology. These tests are often performed routinely by many
      providers with variable methods and interpreted in a variety of ways. Several
      commonly performed provocative tests include Spurling's Neck Compression Test,
      Shoulder Abduction (Relief) Test, Neck Distraction Test, L'hermitte's Sign,
      Hoffmann's Sign and Adson's Test. This review describes some specialized
      provocative tests with comprehensive literature review. The goal of this review
      is to develop standardization in the performance and clinical use of these tests.
      Each of the tests described in this manuscript apparently originated from the
      anecdotal observations of experienced, well respected clinicians. However, only
      few studies have been performed addressing the interexaminer reliability or
      validity of these tests. The existing literature appears to indicate high
      specificity, low sensitivity, and good to fair interexaminer reliability for
      Spurling's Neck Compression Test, the Neck Distraction Test, and The Shoulder
      Abduction (Relief) Test when performed as described. For Hoffman's Sign, the
      existing literature does not address interexaminer reliability but appears to
      indicate fair sensitivity and fair to good specificity. For L'hermitte's Sign and
      Adson's Test, not even tentative statements can be made with regard to
      interexaminer reliability, sensitivity, and specificity, based on the existing
      literature. It is concluded that more research is indicated to understand the
      clinical utility of all the provocative tests employed in the physical
      examination of the neck and cervical spine.

PMID- 16883382
TI  - Pseudo-Kummel's disease: a unique application for vertebroplasty.
AB  - Compression fractures of the vertebrae are a major public health concern. There
      are approximately 700,000 compression fractures of the vertebrae diagnosed on an
      annual basis in the thoracolumbar spine. The etiology of senile osteoporosis is
      multifactorial with the most significant reason being age-related bone loss.
      Multiple effects of compression fractures include acute and chronic pain
      syndromes, inability to perform activities of daily living, insomnia and
      depression. Conventional treatment concepts relate to immobilization of the
      spine, medical pain control, bracing of the back and physical therapy.
      Vertebroplasty was developed in the 1980s as a treatment for painful cervical
      hemangiomas in France. Vertebroplasty has been utilized since 1993 to treat
      painful, osteoporotic compression fractures. In 1891, Kummell described the
      disease with a posttraumatic osteitis in which patients developed a painful
      kyphosis after a period of being symptom free. Inferential evidence includes that
      vertebrae in this disease are being subjected to a form of avascular necrosis
      with intraosseous vacuum phenomenon. Patients with Kummell's disease, treated
      with vertebroplasty, have been reported to do very well. In a patient with an
      advanced case of vertebrae plana, without so intending, authors placed air into
      the vertebral body and created so-called pseudo-Kummell's disease. This case
      report describes with high risk or extreme vertebroplasty to alleviate
      symptomatology. It is concluded that as the clinical experience with percutaneous
      vertebroplasty continues to expand, the approaches to treatment can become more
      focused on the specific disease state and specific treatment paradigms.

PMID- 16883383
TI  - Pedicle lesion in the toddler: a radiologic review.

PMID- 16883384
TI  - Model policy guidelines for opioid addiction treatment in the medical office.

PMID- 16883385
TI  - Multidisciplinary collaboration between pain physicians and psychologists:
      ageless wisdom for the new millennium.

PMID- 16883388
TI  - Theory for non-equilibrium statistical mechanics.
AB  - This paper reviews a new theory for non-equilibrium statistical mechanics. This
      gives the non-equilibrium analogue of the Boltzmann probability distribution, and
      the generalization of entropy to dynamic states. It is shown that this so-called
      second entropy is maximized in the steady state, in contrast to the rate of
      production of the conventional entropy, which is not an extremum. The
      relationships of the new theory to Onsager's regression hypothesis, Prigogine's
      minimal entropy production theorem, the Langevin equation, the formula of Green
      and Kubo, the Kawasaki distribution, and the non-equilibrium fluctuation and work
      theorems, are discussed. The theory is worked through in full detail for the case
      of steady heat flow down an imposed temperature gradient. A Monte Carlo algorithm
      based upon the steady state probability density is summarized, and results for
      the thermal conductivity of a Lennard-Jones fluid are shown to be in agreement
      with known values. Also discussed is the generalization to non-equilibrium
      mechanical work, and to non-equilibrium quantum statistical mechanics. As
      examples of the new theory two general applications are briefly explored: a non
      equilibrium version of the second law of thermodynamics, and the origin and
      evolution of life.

PMID- 16883389
TI  - Self-association of block copoly(oxyalkylene)s in aqueous solution. Effects of
      composition, block length and block architecture.
AB  - The article deals with the association behaviour in dilute aqueous solution of
      block copoly(oxyalkylene)s in which hydrophilic poly(ethylene oxide) is combined
      with hydrophobic poly(propylene oxide), poly(1,2-butylene oxide) or poly(styrene
      oxide). Polymers with three simple architectures are considered, i.e. copolymers
      of type EmAn, EmAnEm and AnEmAn, where E denotes an oxyethylene unit, A denotes a
      hydrophobic oxyalkylene unit, and the subscripts m and n denote number-average
      block lengths in repeat units. The aim is to examine how composition, block
      length and block architecture govern two fundamental properties, critical micelle
      concentration (cmc) and micelle association number (N), for systems which are in
      dynamic equilibrium. Copolymers with properties known to be greatly affected by
      heterogeneity in composition are excluded from consideration. A uniform pattern
      of behaviour emerges when log(cmc) is plotted against reduced hydrophobic block
      length (x), consistent with the micellisation equilibrium changing from one
      between unimers and multimolecular micelles at low values of x, to one between
      unimolecular micelles and multimolecular micelles at high values of x. Support
      for this model is provided by the enthalpy of micellisation, values of which fall
      effectively to zero as x is increased. Values of the micelle association number
      are used to define a critical hydrophobic block length for micellisation (n(cr))
      for each class of diblock copolymers, values of which apply equally well to the
      half-length of the central block of corresponding EmAnEm triblock copolymers.
      Given these values, and irrespective of block architecture, the overall scaling
      law for the weight-average association number of the micelles is shown to be Nw =
      n'(1.07)m(-0.63) where m is the length (or half-length) of the hydrophilic block,
      and n' is the effective length of the hydrophobic block, equal to its length (or
      half-length) minus the critical length, i.e. n' = n-n(cr).

PMID- 16883390
TI  - A new structure of water layer on Cu(111) electrode surface during hydrogen
      evolution.
AB  - A layered structure of water molecules formed on a Cu(111) electrode surface
      during hydrogen evolution in sulfuric acid solution was studied by surface X-ray
      diffraction and infrared reflection absorption methods. Water molecules in the
      surface layers take a closest pack-like stacking structure with nearest-neighbor
      oxygen-oxygen distances in intra-(0.322(5) nm) and inter-(0.275(15) nm) layers of
      multi-domains; the infrared spectra of the layered water on the Cu electrode
      surface showed the existence of free OH(OD) and hydrogen-bonded OH(OD) of water
      molecule.

PMID- 16883391
TI  - Propagation with distributed Gaussians as a sparse, adaptive basis for higher
      dimensional quantum dynamics.
AB  - A simple quantum wavepacket propagation algorithm is presented, designed to
      produce a very compact, non-direct product representation in higher-dimensional
      cases. Instead of moving basis functions around, localized basis functions at pre
      defined centers are added to and deleted from the representation, generating an
      active basis function set strictly localized to the region where the moving
      wavepacket has significantly non-zero values. Simple one-dimensional examples
      prove this property, as well as the ability of the algorithm to accommodate
      splitting and rejoining of an arbitrary number of wavefunction pieces, and
      tunnelling through potential energy barriers. It is argued that future
      applications to higher-dimensional examples will be less expensive than with
      traditional direct-product bases, since making the basis adaptive has a lower
      scaling than the elementary steps necessary for any propagation algorithm itself.

PMID- 16883393
TI  - Threshold photoelectron photoion coincidence spectroscopy and selected ion flow
      tube cation-molecule reaction studies of cyclic-C4F8.
AB  - Using tunable vacuum-UV radiation from a synchrotron, the threshold photoelectron
      and threshold photoelectron photoion coincidence (TPEPICO) spectra of cyclic-C4F8
      in the range 11-25 eV have been recorded. The parent ion is observed very weakly
      at threshold, 11.60 eV, and is most likely to have cyclic geometry. Ion yield
      curves and branching ratios have been determined for five fragments. Above
      threshold, the first ion observed is C3F5+, at slightly higher energy C2F4+, then
      successively CF+, CF2+ and CF3+ are formed. The dominant ions are C3F5+ and
      C2F4+, with the data suggesting the presence of a barrier in the exit channel to
      production of C3F5+ whilst no barrier to production of C2F4+. In complementary
      experiments, the product branching ratios and rate coefficients have been
      measured in a selected ion flow tube (SIFT) at 298 K for the bimolecular
      reactions of cyclic-C4F8 with a large number of atomic and small molecular
      cations. Below the energy where charge transfer becomes energetically allowed,
      only one of the ions, CF2+, reacts. Above this energy, all but one of the
      remaining ions react. Experimental rate coefficients are consistently greater
      than the collisional values calculated from modified average dipole orientation
      theory. The inclusion of an additional ion-quadrupole interaction has allowed
      better agreement to be achieved. With the exception of N+, a comparison of the
      fragment ion branching ratios from the TPEPICO and SIFT data suggest that long
      range charge transfer is the dominate mechanism for reactions of ions with
      recombination energy between 12.9 and 15.8 eV. For all other ions, either short
      range charge transfer or a chemical reaction, involving cleavage and making of
      new bond(s), is the dominant mechanism.

PMID- 16883392
TI  - Absorption cross sections for the A 2A'' (0,9(0),0) <-- X 2A' (0,0(1),0) band of
      the HCO radical.
AB  - Absorption cross sections for the A 2A'' (0,9(0),0) <-- X 2A' (0,0(1),0) band of
      HCO were determined at 295 K using pulsed laser photolysis combined with cavity
      ring-down spectroscopy. Formyl radicals (HCO) were produced from the reaction of
      atomic chlorine, generated by photolysis of Cl2 at 335 nm, with formaldehyde. The
      concentration of HCO was calibrated using two independent photochemical methods.
      The peak cross section of the P8 line was determined to be (1.98 +/- 0.36) x 10(
      18) cm2, and the intensity of the entire band was normalized to this line. The
      quoted 2 sigma uncertainty includes estimated systematic errors. Comparisons to
      previously reported values of HCO cross sections in this band are discussed.

PMID- 16883394
TI  - Dielectric scaling in polyelectrolyte solutions with different solvent quality in
      the dilute concentration regime.
AB  - In this note, we present a set of radiowave dielectric spectroscopy measurements
      of two dilute, differently-charged polyelectrolyte solutions, under different
      solvent conditions. We have found that both the dielectric strength, Delta
      epsilon, and the relaxation time, tau(ion), of the dielectric relaxation process
      associated with the counterion polarization along a length scale of the order of
      the correlation length obey the scaling laws with the polyion concentration,
      according to the Ito model. This is verified with good accuracy independently of
      the quality of the solvent, which has been varied from poor to good solvent
      conditions. This finding supports evidence to the fact that, in dilute solutions,
      the counterion polarization is independent of the polyion concentration, in spite
      of what occurs at the semi-dilute concentrations.

PMID- 16883395
TI  - Two-dimensional electrochemical turbulence during the electrodissolution of metal
      disk electrodes: Model calculations.
AB  - We present numerical studies of the spatio-temporal dynamics of disk electrodes
      with local limit cycle oscillations. The simulations are done with a realistic 3
      D geometry of the electrochemical cell and disk-shaped working electrodes (WE).
      Spatio-temporal chaos is shown to exist from a critical electrode size onwards.
      It is analyzed by Karhunen-Loeve decomposition and Hilbert transform. The former
      shows that the chaos becomes more complex with increasing system size, the latter
      allows features that generate the spatio-temporal complexity to be identified,
      namely, spatially extended 1-D phase defects and topological defects.

PMID- 16883396
TI  - In-situ UV-visible study of Pd nanocluster formation in solution.
AB  - The formation of Pd nanoclusters in solution is studied. This system has two
      types of light-absorbing species: Pd ions which absorb light via electronic
      transitions and Pd clusters and aggregates which absorb light via valence
      conduction transitions and also scatter light due to their nanometric dimensions.
      Here we monitor these dynamic changes using UV-visible spectroscopy. The
      reduction and clustering concentration profiles are extracted from the raw data
      using a combination of net analyte signal (NAS) and principal component analysis
      (PCA) methods. PdCl2, Pd(OAc)2 and Pd(NO3)2 are used as Pd2+ precursors and
      various tetra-n-octylammonium carboxylates are applied as reducing and
      stabilising agents. This in situ approach enables the quantification of both the
      reduction of the Pd2+ ions and the growth of the Pd clusters. Kinetic models that
      account for ion reduction, cluster growth and aggregation are presented and the
      influence of the counteranions and the reducing agents on these processes is
      discussed.

PMID- 16883398
TI  - The first complexes and cyclodimerisations of methylphosphaalkyne (P[triple
      bond]CMe).
AB  - The first complexes and cyclodimerisations of methylphosphaalkyne, P[triple
      bond]CMe, are reported to arise from its reactions with a range of platinum(0)
      complexes and [W(CO)5(THF)]. A number of differences between the chemistry of
      this phosphaalkyne and that of its bulkier analogues have been highlighted and
      explained on steric grounds.

PMID- 16883397
TI  - Direct IR observation of vibrational properties of carbonyl species formed on Pd
      nano-particles supported on amorphous carbon: comparison with Pd/SiO2-Al2O3.
AB  - By diluting optically opaque carbon-supported Pd particles in silica Aerosil we
      succeeded in observing the IR bands of adsorbed carbonyls and extracting
      information on the particle dispersion. Comparison with literature single crystal
      data and with silica-alumina supported Pd allowed us to make an assignment in
      terms of linear and 2-fold bridged carbonyls formed on Pd(111) and Pd(100) faces.
      Two Pd/C samples have been investigated. The relative intensities of the two
      carbonyl families observed on the two samples are consistent with the Pd
      dispersion independently measured with CO chemisorption, TEM and EXAFS analysis.

PMID- 16883399
TI  - Synthesis and structure of heterometallic complexes (RhFe, CoFe) containing
      bridging 1,2-dicarba-closo-dodecarborane-1,2-dichalcogenolato ligands.
AB  - The prototype hetero-binuclear complexes containing metal-metal bonds,
      {CpRh[E2C2(B10H10)]}[Fe(CO)3] (Cp = Cp* = eta 5-Me5C5, E = S(5a), Se(5b); Cp = Cp
      = eta 5-1,3-tBu2C5H3, E = S(6a), Se(6b)) and {CpCo[E2C2(B10H10)]}[Fe(CO)3] (Cp =
      Cp* = eta 5-Me5C5, E = S(7a), Se(7b); Cp = Cp = eta 5-C5H5, E = S(8a), Se(8b))
      were obtained from the reactions of 16-electron complexes CpRh[E2C2(B10H10)] (Cp
      = Cp*, E = S(1a), Se(1b); Cp = Cp, E = S(2a), Se(2b)), CpCo[E2C2(B10H10)] (Cp =
      Cp*, E = S(3a), Se(3b); Cp = Cp, E = S(4a), Se(4b)) with Fe(CO)5 in the presence
      of Me3NO. The molecular structures of {Cp*Rh[E2C2(B10H10)]}[Fe(CO)3] (E = S(5a),
      Se(5b)), {CpRh[S2C2(B10H10)]}[Fe(CO)3] (6a) {Cp*Co[S2C2(B10H10)]}[Fe(CO)3] (7a)
      and {CpCo[S2C2(B10H10)]}[Fe(CO)3] (8a) have been determined by X-ray
      crystallography. All these complexes were characterized by elemental analysis and
      IR and NMR spectra.

PMID- 16883400
TI  - Amine mediated proton transfer reaction and C-Cl bond activation of solvent
      chloroform by a trinuclear copper(II) complex of a glucopyranosylamine derived
      ligand.
AB  - An amine mediated C-Cl bond activation process of the solvent chloroform has been
      explored by a coordinatively labile trinuclear Cu(II) complex,
      [Cu3(L1)2(MeOH)(H2O)] (1), derived from N-(3-tert-butyl-2-hydroxybenzylidene)-4,6
      O-ethylidene--D-glucopyranosylamine (H3L1). The effect of activation is extremely
      high with methylamine, resulting in the formation of [Cu(MeNH2)5]Cl2 (2) and
      [Cu(L2)2] (3; HL2 = 2-tert-butyl-6-[(methylimino)methyl]phenol), however, under
      identical conditions it is moderate with ethylamine resulting in the isolation of
      crystals of the intermediate amine bound trinuclear copper(II) complex,
      [Cu3(L1)2(EtNH2)2(MeOH)2] (5), which was further converted into the mononuclear
      complex, [Cu(HL1)(EtNH2)] (6), in a novel crystal-to-crystal transformation. The
      successive isolation of the ethylamine-bound tri- and mononuclear complexes, 5
      and 6, supported the occurrence of proton transfer reactions, which might be a
      key step in C-Cl bond activation. The primary and secondary amines, 2
      aminomethylpyridine, N,N-dimethylethylenediamine, and 1,4,7-triazacyclononane,
      also having chelating features further enhance the rate of activation. No
      activation has been noted in the case of triethylamine and N,N,N,N
      tetramethylethylenediamine. Formation of a carbene-trapped compound, 2,6-xylyl
      isocyanide, was confirmed in the reaction of complex 1 with 1,4,7
      triazacyclononane and 2,6-xylidine in CHCl3, suggesting that the C-Cl bond
      cleavage led to the generation of dichlorocarbene. In addition, the mononuclear
      complex 6 has been transformed into a homotrinuclear complex [Cu3(L1)2(MeOH)2] by
      treatment with Cu(II) ions in MeOH/CHCl3, suggesting the possibility that the
      former could be regarded as a suitable metalloligand for heterotrimetallic
      complex synthesis.

PMID- 16883401
TI  - Macropolyhedral boron-containing cluster chemistry. A synthetic approach via the
      auto-fusion of [6,9-(SMe2)2-arachno-B10H12].
AB  - In an attempt to build up borane-based multicluster assemblies, thermolysis of
      [6,9-(SMe2)2-arachno-B10H12] 1 in inert hydrocarbon solution, followed by
      chromatographic separation, has resulted in the isolation not only of the
      previously established single-cluster product from this reaction, [5-(SMe2)-nido
      B10H12] 2 (30%), but also the two two-cluster species [6,9-(SMe2)2-arachno-B10H11
      1-(6-nido-B10H13)] 3 (20%) and [1,6-(nido-B10H13)2] 6 (ca. 0.5%) and the two
      three-cluster species [6,9-(SMe2)2-arachno-B10H10-1,5-(6-nido-B10H13)2] 4 (5%),
      characterized crystallographically, and [6,9-(SMe2)2-arachno-B10H10-1,3-(6-nido
      B10H13)2] 5 (<1%), identified by NMR spectroscopy. An improved crystallographic
      investigation of [5-(SMe2)-nido-B10H12] 2 is also presented. The feasibility of
      the stability of species resulting from multiple adjacent substitution of nido
      decaboranyl units on the [6,9-(SMe2)2-arachno-B10H12] skeleton is tested by DFT
      calculations. In an extension, to attempt the use of pre--linked two-cluster
      compounds as starting substrates, two-cluster [5-(SMe2)-4-(2-nido-B10H13)-nido
      B10H11] 7 (0.6%) has been isolated from the reaction of SMe2 with [1,5-(nido
      B10H13)2], other identified products being compound 1 (39%) and compound 3
      (10.5%).

PMID- 16883402
TI  - Colorimetric recognition of Cu(II) by (2-dimethylaminoethyl)amino appended
      anthracene-9,10-diones in aqueous solutions: deprotonation of aryl amine NH
      responsible for colour changes.
AB  - Chromogenic receptors 2 and 3 undergo distinct colour changes from magenta to
      blue on gradual addition of Cu(II) and can be used as colorimetric probes for
      spectrophotometric and visual analysis of Cu(II) in the presence of biological
      metal ions Na(I), K(I), Mg(II), Ca(II), Fe(II), Zn(II) etc. in aqueous solution
      (methanol-water 1 : 1 v/v). On addition of Cu(II), both 2 and 3 exhibit a
      bathochromic shift of Delta lambda(max) = 114 nm for 2 and Delta lambda(max)= 150
      and 265 nm for receptor 3. The protonation constants and formation constants of
      Cu(II) complexes of receptors 2 and 3 (at pH 7) and the effect of pH on formation
      of these complexes has been determined by the combination of UV-vis-pH titrations
      of receptors 2 and 3 and their Cu(II) complexes. These results and the emergence
      of only one peak at 610 nm for 2 and two distinct absorption peaks at 715 and 800
      nm for 3 on addition of Cu(II) unambiguously point to mono- and di-deprotonation
      for 2 and 3, respectively.

PMID- 16883403
TI  - Metal-organic frameworks incorporating Cu3(mu3-OH) clusters.
AB  - Interaction of 4,4-bi(1,2,4-triazole) (btr) with copper(II) chloride (bromide) in
      aqueous or aqueous alcohol media led to a series of coordination polymers
      featuring the formation of mu 3-hydroxotricopper(II) clusters and their
      integration into 3D frameworks. These unprecedented structures originate in the
      propagation of trigonal hydroxotricopper(II) clusters bridged by tri- or
      tetradentate organic ligands. Complex [{Cu3(mu3-OH)}{Cu3(mu3-O)}(mu4
      btr)3(H2O)4(OH)2Cl6]Cl.0.5H2O adopts a structure of SrSi2 topology, with eight
      fold interpenetration of the coordination frameworks. The structure of [{Cu3(mu3
      OH)}2(mu3-btr)6(mu4-btr)(mu-X)X4]X5.nH2O (X = Br, n = 6; X = Cl, n = 8) involves
      2D coordination layers [{Cu3(mu3-OH)}(mu3-btr)3]n with an exceptional (3,6)-net
      topology, which are cross-linked by tetradentate btr ligands and bridging
      chloride (bromide) ions.

PMID- 16883404
TI  - 1,3,2-Diazaborolyl-functionalized thiophenes and dithiophenes: synthesis,
      structure, electrochemistry and luminescence.
AB  - Reaction of 2-bromo-1,3-diethyl-1,3,2-benzodiazaborole (1) with equimolar amounts
      of thienyl lithium or 2,2-dithienyl lithium led to the generation of
      benzodiazaboroles 2 and 3 which are functionalized at the boron atom by a 2
      thienyl or a 5-(2,2-dithienyl) unit. Similarly 2-bromo-1,3-diethyl-1,3,2
      naphthodiazaborole (4) and thienyl lithium or 2,2-dithienyl lithium afforded the
      naphthoborolyl-substituted thiophene 5 or dithiophene 6. Treatment of 2,5
      bis(dibromoboryl)-thiophene 7 with 2 eq. of tBuN=CH-CH=NtBu in n-hexane followed
      by sodium amalgam reduction of the obtained bis(diazaborolium) salt 8 gave the
      2,5-bis(diazaborolyl)thiophene 9. The 2,5-bis(diazaborolidinyl)-thiophene 10
      resulted from the cyclocondensation of 7 with 2 eq. of N,N-di-tert
      butylethylenediamine in the presence of NEt3. Analogously, cyclocondensation of 7
      with N,N-diethylphenylenediamine gave the bis(benzodiazaborolyl) functionalized
      thiophene 11. The novel compounds were characterized by elemental analysis and
      spectroscopy (1H-, 11B-, 13C-NMR, MS and UV-VIS). The molecular structure of 3
      was elucidated by X-ray diffraction. Cyclovoltammograms show an irreversible
      oxidation wave at 298-598 vs. Fc/Fc+. The borolylated thiophenes and dithienyls
      show intense blue luminescence with Stokes shifts of 30-107 nm.

PMID- 16883405
TI  - Rhodium, palladium and platinum complexes of tris(pyridylalkyl)amine and
      tris(benzimidazolylmethyl)amine N4-tripodal ligands.
AB  - To investigate the influence of a potentially N4-tripodal amine ligand on the
      structure and internal exchange processes of its complexes with late transition
      metals, five rhodium, six palladium and two platinum complexes have been prepared
      from seven alkyl-bridged N-heterocyclic amine tripodal ligands: tris(2
      pyridylmethyl)amine, (2-(2-pyridylethyl))bis(2-pyridylmethyl)amine, bis(2-(2
      pyridylethyl))-2-pyridylmethylamine, bis(2-(2-pyridylethyl))amine, ((6
      (hydroxymethyl)-2-pyridyl)methyl)bis(2-pyridylmethyl)amine, tris(2
      benzimidazolylmethyl)amine (tbima) and tris(3-ethyl-2-benzimidazolylmethyl)amine.
      Single-crystal X-ray diffraction studies were completed for ten complexes: the d6
      rhodium(III) complexes are octahedral with kappa 4 N-bound ligands, whereas the
      d8-palladium(II) and d8-platinum(II) complexes are square planar, kappa 3 N-bound
      by the tripodal ligand with a dangling N-donor leg, except for the unusual
      [Pd2(tbima)2Cl2]Cl2 dimer in which each palladium(II) ion is square planar and
      bound by two benzimidazole legs from one tbima ligand, one leg from the other
      tbima ligand and a chloride ancillary ligand. Cation bilayers are a common
      structural motif in the crystal structures. Variable-temperature 1H NMR studies
      reveal exchange occurs between the coordinated and dangling N-donor legs in the
      palladium and platinum complexes. Exchange free energy (Delta G++ c) values have
      been calculated and some general rules governing the favoured complex structures
      and exchange pathways elucidated. The palladium(II) and platinum(II) complexes of
      a ligand with an pyridylethyl leg are unstable with respect to elimination of
      vinylpyridine.

PMID- 16883406
TI  - A new family of luminescent compounds: platinum(II) imidoylamidinates exhibiting
      pH-dependent room temperature luminescence.
AB  - The imidoylamidinate platinum(II) compounds [Pt{NH=C(R)NC(Ph)NPh}2] (R = CH2Ph 2,
      p-ClC6H43, Ph 4) were prepared by the reaction of the appropriate trans
      [PtCl2(RCN)2] with 4 equiv of the amidine PhC(NH)NHPh giving 2-4 and 2 equivs of
      the salt PhC(=NH)NHPh.HCl. We also synthesized, by the double alkylation of 4
      with MeOSO2CF3, complex [Pt{NH=C(Ph)N(Me)C(Ph)=NPh}2][CF3SO3]2 (5) which models
      the bis-protonated form of 4. The complexes were characterized by 1H, 13C NMR,
      and IR spectroscopies, FAB-MS and by C, H, N elemental analysis. The X-ray
      crystallography of 4.2CH2Cl2 enables the confirmation of the square planar
      coordination geometry of the metal center with almost planar imidoylamidine
      ligands, while in 5.2CHCl3 the planarity of the metallacycles is lost and and the
      central N atom is sp3-hybridized. The imidoylamidinate complexes represent a new
      family of Pt(II)-based luminescent complexes and they are emissive at room
      temperature both in solution and in the solid state, with an emission quantum
      yield ranging from 3.7 x 10(-4) to 6.2 x 10(-2) in methanol solution; the
      emission intensity is pH-dependent, being quenched at low pH. UV-visible and
      luminescence spectroscopies indicate that the lowest excited state of these
      compounds is 3MLCT or 3IL with significant MLCT character, with emission
      lifetimes of a few micros. A blue shift of both the absorption and emission with
      increasing solvent polarity and with decreasing pi-electron withdrawing
      properties of the ligand substituent was observed.

PMID- 16883407
TI  - Synthesis and characterization of zinc AP-MOCVD precursors and their utility in
      the growth of ZnO.
AB  - A novel beta-ketoimine, 4-N-(n-butylamino)-3-penten-2-one (1), and beta
      enaminoester, Ethyl 3-N-(isopropylamino)-2-butenoate (2), were synthesized by the
      reaction of the 2,4-pentanedione or ethyl 3-oxo butanoate with the n-butyl and
      isopropyl amine, respectively. The isolated free ligands 1 and 2 were reacted
      with diethylzinc to afford Zn(CH3C(NCH2CH2CH2CH3)CHCOCH3)2 (3) and
      Zn(CH3C(NCH(CH3)2)CHC(O)OCH2CH3)2 (4) respectively. The isolated zinc complexes,
      3 and 4, were characterized by elemental analysis, NMR, and MALDI-TOFMS. The
      molecular structure of 3 and 4 were determined via single crystal X-ray
      diffraction which revealed both compounds to be four coordinate, monomeric and
      homoleptic in the solid state. TG analysis showed the air stable compounds to be
      thermally robust as they both sublimed in a one-step process at atmospheric
      pressure. The compounds were utilized in the growth of ZnO via AP-MOCVD in the
      absence of additional oxidant. The carbon content of the film grown from 3 as
      determined by XPS was 26.2% while that of the film grown by 4 was 8.71%.

PMID- 16883408
TI  - Preparation and characterization of mononuclear Co, Ni, and Zn complexes of
      dinucleating macrocyclic hexaaza-dithiophenolate ligands and their open-chain
      derivatives.
AB  - The preparation and characterization of mononuclear complexes of the dinucleating
      24-membered hexazadithiophenolate macrocycles H2L2 and H2L3 and their open-chain
      N3S2 analogues H2L4 and H2L5 are reported. The highly crystalline compounds
      [Ni(L4)] (4), [Ni(L5)] (5), [Co(L5)] (6), [NiH2(L2)]2+ (7), [ZnH2(L2)]2+ (8), and
      [NiH2(L3)]2+ (9) could be readily prepared by stoichiometric complexation
      reactions of the hydrochlorides of the free ligands with the corresponding
      metal(II) dichlorides and NEt3 in methanolic solution. All complexes were
      characterized by X-ray crystallography. Monometallic complexes 4-6 of the
      pentadentate ligands H2L4 and H2L5 feature distorted square pyramidal MN3S2
      structures (tau = 0.01 to 0.44). Similar coordination geometries are observed for
      the macrocyclic complexes 7-9 of the octadentate ligands H2L2 and H2L3. The two
      hydrogen atoms in 7-9 are attached to the noncoordinating benzylic amine
      functions and are hydrogen bonded to the metal-bound thiophenolate functions. A
      comparison of the structures of 4-9 reveals that the macrocycles L2 and L3 have a
      rather flexible ligand backbone that do not confer unusual coordination
      geometries on the metal ions. We also report on the ability of the monometallic
      complexes 7 and 8 to serve as starting materials for the preparation of dinuclear
      complexes.

PMID- 16883409
TI  - Oxidation-state and metal-ion dependent stereoisomerization in oxo molybdenum and
      tungsten complexes of a bulky alkoxy heteroscorpionate ligand.
AB  - Monooxo Mo(V) complexes of a N2O heteroscorpionate ligand designated (L10O) are
      found to exist as isolable cis and trans isomers. We have been able to trap the
      kinetically labile cis isomer and follow its isomerization to the
      thermodynamically more stable trans form. We have also followed the kinetics of
      isomerization between the cis and trans isomers of the corresponding dioxo Mo(VI)
      and W(VI) species. Here the trans is the labile isomer that spontaneously
      converts to the thermodynamically more stable cis. It is observed that at 60
      degrees C in DMSO the Mo(VI) complex isomerizes approximately 6.5 times faster
      than the Mo(V) and nearly 5 times faster than the corresponding W(VI) analogs.
      The temperature dependence to the kinetics of the Mo(V) and Mo(VI) isomerizations
      give activation parameters that are similar for both oxidation states and
      consistent with those previously observed in [(L1O)MoOCl2] suggesting a similar
      twist mechanism is operating in all cases. Thus there are oxidation state, metal
      ion and donor atom dependent differences in isomeric stability that could have
      significant implications for understanding the mechanisms of both enzymatic and
      nonenzymatic oxo atom transfer reactions catalyzed by complexes of Mo, W and Re.

PMID- 16883411
TI  - Single-site photocatalytic solids for the decomposition of undesirable molecules.
AB  - Photocatalytic solids, in which the absorption occurs at isolated, spatially well
      separated centres, are particularly useful catalysts for effecting reactions that
      are of prime importance in both remedial and preparative contexts. These are
      qualities that they share with single-site (thermally-activated) heterogeneous
      catalysts; but they have the added advantage of being more readily probed during
      the actual processes of catalytic turnover, since they generally function under
      ambient conditions, unlike most conventional solid catalysts which usually
      operate at elevated pressures and temperatures. Thus, they are amenable to
      investigation by (in situ) X-ray absorption (XAFS), FT-IR, UV-Vis, and EPR
      spectroscopic studies as well as to photoluminescence measurement. This affords
      greater insight into the mechanisms of the photocatalytic reactions as we
      illustrate in this short review. Open-structure solids such as mesoporous silica
      and zeolitic aluminosilicates offer a generally applicable strategy to design new
      single-site photocatalysts such as those described here for the decomposition of
      NO to N2 and O2 and for the selective oxidation of CO in the presence of H2.

PMID- 16883412
TI  - Photochemical energy conversion: from molecular dyads to solar cells.
AB  - Photochemical approaches to solar energy conversion are currently making rapid
      progress, increasing not only academic but also commercial interest in molecular
      based photovoltaic solar cells. This progress has been achieved not only by
      increased understanding of the physics and physical chemistry of device function
      but also through advances in chemical and materials synthesis and processing,
      which now allows the design and fabrication of increasingly sophisticated device
      structures organised on the nanometer length scale. In this feature article, we
      review some progress in this field, focusing in particular upon the electron
      transfer dynamics which underlie the function of dye-sensitised, nanocrystalline
      solar cells. The article starts by building upon the parallels between the
      function of such devices and the function of simple donor/acceptor molecular
      systems in solution. We then go on to discuss the optimisation of device
      function, and in particular the use of self-assembly-based strategies to control
      interfacial electron-transfer kinetics.

PMID- 16883413
TI  - Fluorinated liquid crystals formed by halogen bonding.
AB  - New, halogen-bonded fluorinated mesogens are reported; the expected microphase
      separation associated with perfluoroalkyl chains is surprisingly absent in the
      mesophase.

PMID- 16883414
TI  - Cooking cellulose in hot and compressed water.
AB  - Crystalline-to-amorphous transformation of cellulose in water, just like that for
      starch upon cooking called gelatinisation, is revealed at 320 degrees C and 25
      MPa.

PMID- 16883415
TI  - Skeletal diversity construction via a branching synthetic strategy.
AB  - A branching synthetic strategy was used to efficiently generate structurally
      diverse scaffolds, which span a broad area of chemical descriptor space, and
      their biological activity against MRSA was demonstrated.

PMID- 16883416
TI  - Unusually high stability of a poly(alkylquaterthiophene-alt-oxadiazole)
      conjugated copolymer in its n and p-doped states.
AB  - Incorporation of electron accepting units (oxadiazole) into the 2,5-thienylene
      conjugated chain leads to a significant improvement in the n-doping-undoping
      redox stability of the resulting polymer.

PMID- 16883417
TI  - An azido-bridged disc-like heptanuclear cobalt(II) cluster: towards a single
      molecule magnet.
AB  - A disc-like heptanuclear Co(II)-cluster, [Co7(bzp)6(N3)9(CH3O)3].2ClO4.2H2O (1)
      (bzp = 2-benzoyl pyridine), mixed-bridged by 3/4 azides (mu1,1 and mu1,1,1) and
      1/4 mu1,1,1-methanol, shows slow relaxation at static zero and non-zero fields
      below 6 K, towards single molecule magnet behavior.

PMID- 16883419
TI  - Guest-induced formation of an icosahedral coordination cage.
AB  - A coordination cage with an elusive icosahedral geometry was obtained by K+
      induced rearrangement of a hexanuclear [(cymene)Ru(pyridine-3,5-dicarboxylate)]6
      complex.

PMID- 16883418
TI  - The first route to large pore metal phosphonates.
AB  - The first large pore (free diameter > 7 A) metal phosphonates have been prepared
      as divalent metal N,N'-piperazinebis(methylenephosphonate)s that possess pores
      greater than ca. 10 A in free diameter, are stable up to 400 degrees C and offer
      a route to chiral adsorbents and catalysts.

PMID- 16883420
TI  - Electrochemical synthesis and characterization of transparent nanocrystalline
      Cu2O films and their conversion to CuO films.
AB  - Transparent nanocrystalline Cu2O films (Eg = 2.6 eV) were electrodeposited from a
      dimethyl sulfoxide medium; these films exhibit interesting optical and
      photoelectrochemical properties, and can be converted to transparent CuO films.

PMID- 16883421
TI  - Selective recognition and electrochemical sensing of dicarboxylates with a
      ferrocene-based bis(o-trifluoroacetylcarboxanilide) receptor.
AB  - A ferrocene-based bis(o-trifluoroacetylcarboxanilide) receptor selectively
      recognizes m-phenylene diacetate through cooperative binding; the receptor also
      displays a significant negative shift in the oxidation potential of ferrocene
      upon the guest binding.

PMID- 16883423
TI  - The 6-amino-6-methyl-1,4-diazepine group as an ancillary ligand framework for
      neutral and cationic scandium and yttrium alkyls.
AB  - The 6-amino-6-methyl-1,4-diazepine framework is a readily available neutral 6
      electron ligand moiety, suitable to support cationic group 3 metal alkyl
      catalysts; it also provides convenient access to tri- and tetradentate
      monoanionic ligand derivatives.

PMID- 16883422
TI  - Gelation of La(III) cations promoted by 5-(2-pyridyl)tetrazolate and water.
AB  - Addition of water to the product formed when LaCl3 and 1H-5-(2-pyridyl)tetrazole
      (LH) were treated with an excess of triethylamine in ethanol, resulted in the
      reversible formation of a hydrogel, which when further treated with EtOH-iPrOH
      produced crystals of [LaL3(H2O)3].(H2O)4, as determined by X-ray crystallography.

PMID- 16883424
TI  - An alkynylboronic ester cycloaddition route to functionalised aromatic boronic
      esters.
AB  - A series of functionalised aromatic boronic esters have been prepared via the
      regioselective cycloaddition of 2-pyrones with alkynylboronates.

PMID- 16883425
TI  - Racemic iron(III) and cobalt(III) complexes containing a new pentadentate
      "helmet" phthalocyaninato ligand.
AB  - Solvothermal reactions of iron(II) acetate tetrahydrate and cobalt(II) acetate
      tetrahydrate with 1,2-dicyanobenzene in methanol solution result in the formation
      of racemic six-coordinate iron(III) and cobalt(III) complexes, respectively, with
      a new bicyclic pentadentate 14,28-[1,3-diiminoisoindolinato]phthalocyaninato
      ligand.

PMID- 16883427
TI  - Anionic ring-opening polymerization of a strained phosphirene: a route to
      polyvinylenephosphines.
AB  - A strained 1-phenyl-2,3-dimethylphosphirene undergoes anionic ring-opening
      polymerization upon initiation with n-butyl lithium at ambient temperature to
      yield polyvinylenephosphine, an unsaturated organophosphorus polymer.

PMID- 16883426
TI  - Vanadyl C and N-capped tris(phenolate) complexes: influence of pro-catalyst
      geometry on catalytic activity.
AB  - Vanadyl complexes of C or N-capped tripodal ligands, possessing distorted
      tetrahedral geometry at vanadium, serve as extremely active, thermally robust pro
      catalysts for ethylene homo- and ethylene/propylene copolymerisation, whereas
      pseudo-octahedral pro-catalysts produce far lower activities.

PMID- 16883428
TI  - Regio-controlled ring-opening polymerization of perfluoroalkyl-substituted
      epoxides.
AB  - Highly fluorinated epoxides were polymerized under mild conditions
      regioregularly, which gave easy access to isotactic polymers by using optically
      pure epoxides.

PMID- 16883429
TI  - Novel aziridination of olefins: direct synthesis from sulfonamides using t-BuOI.
AB  - tert-Butyl hypoiodite (t-BuOI) was found to be a powerful reagent for synthesis
      of aziridines from olefins and sulfonamides. The aziridination of olefins was
      achieved by using sulfonamides with t-BuOI. Our preliminary findings represent
      the example of metal-free aziridination of olefins with readily accessible
      sulfonamides as a nitrogen source.

PMID- 16883430
TI  - Eu(III) dithiocarbamate complex and N-p-tolylsulfonylphenylalanine as a novel
      chiral catalyst for the asymmetric synthesis of cyanohydrins.
AB  - The use of a new chiral lanthanide complex derived from a europium
      dithiocarbamate complex and a N-tosylated amino acid for the asymmetric synthesis
      of cyanohydrins is described. In some cases, high enantioselectivities were
      observed.

PMID- 16883431
TI  - Ultrathin molecularly imprinted polymer sensors employing enhanced transmission
      surface plasmon resonance spectroscopy.
AB  - An ultrathin novel nanosensor (31.5 +/- 4.1 nm thick in the absence of analytes),
      employing a molecularly imprinted polymer as a recognition element for
      cholesterol and gold nanoparticle enhanced transmission surface plasmon resonance
      spectroscopy for detection, was constructed.

PMID- 16883432
TI  - Dithiaethyneazuliporphyrin--a contracted heterocarbaporphyrin.
AB  - Dithiaethyneazuliporphyrin, the first contracted carbaporphyrinoid, has been
      synthesized; the molecule contains an azulene moiety embedded in the
      [18]dithiacarbatriphyrin(4.1.1) macrocyclic framework.

PMID- 16883433
TI  - Synthesis of small palladium nanoparticles stabilized by bisphosphine BINAP
      bearing an alkyl chain and their palladium nanoparticle-catalyzed carbon-carbon
      coupling reactions under room-temperature.
AB  - A new bisphosphine ligand, C8-BINAP, and C8-BINAP-stabilized palladium
      nanoparticles have been prepared; C8-BINAP was found to be an effective
      protecting ligand for preparing and stabilizing palladium nanoparticles with very
      small core size and narrow size distribution and the C8-BINAP-Pd nanoparticles
      behave as an efficient catalyst for carbon-carbon coupling reactions at room
      temperature.

PMID- 16883434
TI  - BiCl3-catalyzed propargylic substitution reaction of propargylic alcohols with C
      , O-, S- and N-centered nucleophiles.
AB  - A general and efficient BiCl3-catalyzed substitution reaction of propargylic
      alcohols with carbon and heteroatom-centered nucleophiles such as allyl
      trimethylsilane, alcohols, aromatic compounds, thiols and amides, leading to the
      construction of C-C, C-O, C-S and C-N bonds, has been developed.

PMID- 16883435
TI  - Immunological diagnosis of vasculitis.
AB  - Inflammation of blood vessels, or vasculitis, is caused by a heterogenous group
      of autoimmune conditions with wide spectrum of systemic, and often overlapping,
      clinical manifestations. Some of these conditions present acutely and result in
      major organ's damage and, therefore, require prompt diagnosis and treatment in
      order to avoid the high morbidity and mortality that otherwise occur. The
      clinical immunology laboratory plays a vital role in the diagnosis of vasculitis.
      Moreover, due to the availability of simple tests, with quick turn around time,
      immunological findings can provide an early picture of the type of vasculitis
      involved thereby allowing initiation of prompt treatment in life threatening
      situations. In the present review, we will outline the various tests available in
      the immunology laboratory for the investigation of vasculitides, discuss the
      assays used to carry out these tests and, finally, comment on the significance of
      the results produced in relation to the diagnosis, or exclusion, of vasculitis.
      We hope that such information would prove of great importance to physicians and
      immunologists alike and lead to more efficient diagnosis of these important and,
      often, life threatening conditions.

PMID- 16883436
TI  - Motor vehicle collisions with large animals.
AB  - Motor vehicle collisions MVC with large animals are a worldwide problem. In this
      review, we aim to analyze the mechanisms and patterns of human injuries caused by
      MVC with large animals and various ways to prevent them. Reported studies on
      large animals that can cause such accidents include the moose, camels, deer, and
      kangaroos. The moose causes a typical rear-and downward deformity of the roof of
      the car. The camel falls on the roof of the car causing cervical and head injury
      to the occupants. Injuries caused by kangaroos and deer are usually mild.
      Injuries may be caused by direct collision with the animal or hitting another
      object when trying to avoid it. Alarming signs, underpasses or overpasses for
      animals, and reflectors that frighten the animals were all used to prevent the
      collisions. Roo-bars are used in Australia to reduce the car damage when hit by a
      kangaroo. Fencing has proven useful in United Arab Emirates. The mechanism of
      injury varies with the size and height of the animal and can be serious.
      Increased awareness of the effects of collision with large animals and ways to
      reduce it has to be promoted.

PMID- 16883437
TI  - Comparison of antigenic sites of the envelope glycoprotein of the Iranian isolate
      of human T-cell leukemia virus type 1 with different subtypes of the virus.
AB  - OBJECTIVE: Human T-cell leukemia virus type 1 (HTLV-1) is an enveloped
      retrovirus, which is associated with a T-cell malignancy known as adult T-cell
      leukemia (ATL). Variation in the HTLV-1 envelope nucleotide sequence has been
      extensively documented and has been used to classify HTLV-1 isolates into
      different subtypes. The virus occurs in at least 3 subtypes, which have been
      named A, B, and C. We conducted this study to compare the antigenic proprieties
      of the Iranian isolate of HTLV-1 with the homologous region of different subtypes
      of the virus. METHODS: This study took place in the Department of Biology,
      College of Sciences, Shiraz University, Iran in 2005. The predicted antigenic
      sites and secondary structure of the envelope glycoprotein of HTLV-1, present in
      Iran, have been compared with the antigenic sites and secondary structure of the
      homologous domains in subtypes A, B, C of the virus. To predict the epitopes of
      glycoproteins, 21 different scales were used. RESULTS: The number of helices in
      the Iranian isolate was equal to the number of these regions in all 3 subtypes,
      but the number of beta-sheets was more than other viruses. One potential
      glycosylation site, on all these studied envelope glycoproteins, was predicted.
      Antigenic sites in the Iranian isolate were almost similar to subtype A of the
      virus and the Iranian isolate of HTLV-1 may be belongs to subtype A. CONCLUSION:
      Our results indicate the similarities and differences between the Iranian and
      other subtypes of HTLV-1. Antigenic sites represent potential candidates for use
      in a peptide vaccine against HTLV-1 glycoproteins and since most of the
      properties of a particular protein depend on its structural properties, this type
      of study can help in better understanding of HTLV-1 isolates present in Iran.

PMID- 16883438
TI  - Lack of evidence of Epstein-Barr virus infection in patients with Castleman's
      disease. Molecular genetic analysis.
AB  - OBJECTIVE: Epstein-Barr virus (EBV) infection is associated with a diverse group
      of malignancies and many lymphoproliferative disorders. Castleman's disease (CD)
      is atypical lymphoproliferative disorder. The role of EBV in the pathogenesis of
      CD is not clear yet. The objective of this study is to investigate the EBV status
      in CD. METHODS: We searched medical records for cases of CD at the Toronto
      General Hospital, Toronto, Canada and King Abdulaziz University Hospital, Jeddah,
      Saudi Arabia. Twenty cases were found. The presence of EBV was analyzed using
      polymerase chain reaction. Polymerase chain reaction were performed at the
      Department of Pathology and Laboratory Medicine, Toronto General Hospital. The
      study started in 2001 and completed in 2005. RESULTS: The age range was 16-90
      years. Seventeen patients manifested the localized form of CD. There were 11
      males 9 females. Epstein-Barr virus genome was detected only in 2 cases; both
      were males and have plasma cell type. One is a localized type and the other is of
      a multicentric type. One patient revealed clonal rearrangement of the
      immunoglobulin H. CONCLUSION: The number of cases is small; however it appears
      that EBV is less likely to play a significant role in the pathogenesis of CD;
      however, it seems to be associated with clonal progression.

PMID- 16883439
TI  - Indeterminate human immunodeficiency virus western blot results in Iranian
      patients with discordant screening assay results.
AB  - OBJECTIVE: The Western blot (WB) assay is the most widely accepted confirmatory
      assay for the detection and confirmation of antibodies to human immunodeficiency
      virus type 1 (HIV-1) and 2 (HIV-2). However, indeterminate WB reactivity to HIV-1
      and HIV-2 proteins may occur in individuals who do not appear to be infected with
      HIV. METHODS: In this study, we describe the results of indeterminate WB
      reactivity in Iranian patients with discordant screening assays. The samples were
      obtained from the Iranian Blood Transfusion Center, Tehran, Iran and evaluated in
      the Biotechnology Process Development Center, Pasteur Institute of Iran, Tehran,
      Iran between 2003 and 2004. A total of 4707 were tested for the presence of HIV-1
      antibodies. RESULTS: Six hundred and four (12.8%) patients tested for HIV were
      positive for HIV-1 antibody. Nine (1.49%) have discordant results among screening
      assays and indeterminate WB results as interpreted by Centers for Disease Control
      and Prevention (CDC) criteria. Most (66.7%) of these indeterminate WB results
      were due to p24 reactivity. However, 2 (22.2%) display reactivity to both gp41
      and gp120 proteins [Positive by World Health Organization (WHO) criteria]. Of 9
      WB assays initially indeterminate by the CDC criteria and with follow-up samples,
      8 (88.8%) became negative when retested subsequently while one (11.1%) remained
      indeterminate for more than a year and were thus considered negative. In
      addition, all the indeterminate samples were negative when assessed by polymerase
      chain reaction assay. CONCLUSION: In general, there was an 88.8% concordance
      between the CDC and WHO criteria for an indeterminate WB result. The CDC II
      criteria best met the specified objectives for diagnosis in our setting.

PMID- 16883440
TI  - Development of an ultra rapid and simple multiplex polymerase chain reaction
      technique for detection of Salmonella typhi.
AB  - OBJECTIVE: To make a rapid and definite diagnosis of Salmonella enteritis, using
      an ultra rapid multiplex polymerase chain reaction (PCR) detection method for
      major Salmonella serotypes, such as Salmonella typhi, Salmonella Typhimurium and
      Salmonella Havana. METHODS: We performed this study at the Research Center of
      Molecular Biology, Institute of Military Medicine, Bagyatallah University of
      Medical Sciences, Iran from June 2004 to July 2005. The PCR primers for tyv
      (rfbE), prt (rfbS) and invA genes were designed and used for the rapid
      identification of Salmonella enterica serovars Typhi and Paratyphi A with
      multiplex PCR. By using simple DNA extraction method in 10 minutes, rapid PCR
      cycles with total cycle times of 35 minutes and rapid electrophoresis procedure
      with simple and very cheap buffer used in 200 to 300 volts for 15 minutes to
      separate the PCR products. RESULTS: The results showed that all reference and
      clinical isolates of Salmonella serovars Typhi and Paratyphi were accurately
      identified by this assay. Specificity analysis revealed no cross-reaction with
      other Enterobacterial strains. The sensitivity of the PCR and the multiplex PCR
      was 1-10 cells. The total time of Multiplex PCR from sample preparation to final
      result is 45-50 minutes. CONCLUSION: These data indicate that the specificity and
      sensitivity of the PCR and the multiplex PCR make them potentially valuable tools
      for diagnosis of Salmonella typhi bacteria and that they may be used for the
      identification of Salmonella enteritidis responsible for sporadic enteritis
      cases.

PMID- 16883441
TI  - Seroprevalence of herpes simplex virus types 1 and 2, Epstein-Barr virus, and
      cytomegalovirus in children with acute lymphoblastic leukemia in Egypt.
AB  - OBJECTIVE: Viral infection, especially caused by herpes viruses, is now
      recognized as an important cause of morbidity and mortality in immunocompromised
      cancer patients. This study aimed at studying seroprevalence of 3 herpes viruses
      Herpes simplex virus types 1 and 2 (HSV 1 and 2), Epstein-Barr virus (EBV), and
      cytomegalovirus (CMV) in children with acute lymphoblastic leukemia (ALL).
      METHODS: We conducted this study on 68 newly diagnosed pediatric patients with
      ALL presented to the Pediatric Oncology Service of National Cancer Institute,
      Cairo University, Egypt from November 2001 to June 2003. We used enzyme-linked
      immunosorbent assay in detecting HSV 1 and 2, CMV, EBV antibodies of both types
      immunoglobulin (Ig) M and IgG detection of DNA for both CMV and EBV by polymerase
      chain reaction was carried out. RESULTS: High seroprevalence of HSV-1 and 2, CMV
      and EBV IgG antibodies in both leukemic children and their control was observed
      (69%, 100%, 83%) and (80%, 100%, 95%). Significantly higher percentage of HSV-1
      and 2 IgM or reactivated infection was found among leukemic children 17/68 (25%)
      compared with normal control 0%. Analysis showed that prevalence of HSV 1 and 2
      IgG increased from 18/33 (54%) in children <5 years to 11/13 (77%) in children
      >10 years, and reactivation of HSV-1 and 2 increased with increasing age from
      1/33 (3%) in children <5 years to 4/13 (30%) in children >10 year. This was in
      contrast to seroprevalence of CMV and EBV IgG which were 100% and 83% in children
      <5 years. No difference in seroprevalence was found among both gender, and no
      difference was found in leukemic patients with granulocytopenia. CONCLUSION: The
      data show a higher exposure to HSV-1 and 2 both primary infections and
      reactivation among ALL children. Therefore, acyclovir prophylaxis could be highly
      effective for seropositive leukemic patients who are undergoing induction
      chemotherapy.

PMID- 16883442
TI  - Determination of fungal frequency and comparison of allergic symptoms related
      with buildings and fungi in Afyon, Turkey.
AB  - OBJECTIVE: To investigate the respiratory symptoms and atopic sensitization to
      fungi and its relation with the building type where school children were
      attending. We also compared the prevalence of sensitization to different fungi
      and respiratory symptoms in 2 different school buildings in a particular area of
      Turkey. METHODS: Using simple random sampling, 301 school children aged 16-19
      years attending a high school in 2 different school buildings (old and new
      buildings) were recruited and agreed to participate in the study. The study was
      conducted in Afyonkarahisar, Turkey from August 2003 to August 2004. Information
      on allergic diseases, building related symptoms and respiratory symptoms of the
      students was collected by questionnaire. Skin prick test (SPT) was performed to
      all students. Fungal concentrations and genera were determined by using Petri
      Plate Gravitational Settling Method. RESULTS: In both buildings, throughout all
      seasons, the most common fungi species seen were Penicillium and Cladosporium.
      When SPT was performed, the most allergen fungi seen in new building was
      Epidermophyton and Penicillium in the old building. The SPT results were also
      related with building related symptoms, except Alternaria. CONCLUSION: When the 2
      groups were compared, it was observed that there were no statistically
      significant differences between them in regards with asthma, allergic diseases,
      building related symptoms, and respiratory symptoms. No significant difference
      was determined between these 2 buildings in accordance to fungus concentration,
      although the humidity rate was higher in new buildings.

PMID- 16883443
TI  - Seroprevalence of fasciolosis and the difference of fasciolosis between rural
      area and city center in Isparta, Turkey.
AB  - OBJECTIVE: To investigate the seroprevalence of fasciolosis and the possible
      causes of differences between rural and city center. METHODS: We undertook a
      multi-stage sampling analysis of data from Isparta, Turkey, between March and
      June 2004. Four hundred and fifteen individuals participants from Isparta center
      and 171 from Asagi Gokdere village were included in the study. Fasciola hepatica
      (F. hepatica) specific antibodies were analyzed using excretory-secretory (ES)
      enzyme-linked immunosorbent assay (ELISA) method. RESULTS: Fasciola hepatica
      antibodies were detected as positive in 10 (2.4%) of 415 people whose sera were
      collected from the city center and 16 (9.3%) of 171 people from Asagi Gokdere
      village. The positivity rates between village and city center were found
      statistically significant. A statistical difference was noted for fasciolosis
      positivity between individuals who have ingested water cress and who have not.
      Fasciolosis was not detected in the individuals who used to wash vegetables with
      water containing vinegar. CONCLUSION: Most of the patients in this region
      reported consumption of uncooked or unwashed water cress. Watering channel is one
      of the major risk factors of fasciolosis. Therefore, it is essential to determine
      the watering systems in this region. Moreover, ES-ELISA would be useful in
      investigating the laboratory diagnosis of fasciolosis.

PMID- 16883444
TI  - Increasing single and multi-antibiotic resistance in Shigella species isolated
      from shigellosis patients in Sana'a, Yemen.
AB  - OBJECTIVE: The epidemiology and antibiotic susceptibility of Shigella species
      changes over time. Updated susceptibility knowledge is necessary for appropriate
      empirical antibiotic treatment. Thus, this research aimed to study these changes
      in 2 time periods with an interval of 10 years. METHODS: Two hundreds and three
      Shigella strains, isolated from stool samples of diarrheic patients at the
      Central Health Laboratory in Sana'a, Yemen in 2 time periods (1993 and 2003) with
      a 10-year interval, were examined for serotyping and drug resistance pattern.
      Resistance patterns of the strains to 12 commonly used antimicrobial agents and
      minimum inhibitory concentrations of the antibiotics were tested. RESULTS:
      Shigella flexneri (60%) was found to be the most common isolate of the total
      Shigella species, followed by Shigella dysenteriae (28.6%) and Shigella boydii
      (11.3%). In Shigella flexneri strains, Shigella flexneri 3 (30.5%) was the most
      prevalent serotype, followed by Shigella flexneri 6 (17.2%), and Shigella
      flexneri 1 (12.3%). All strains were found equally susceptible to cefotaxime,
      ceftriaxone, ciprofloxacin, and gentamicin, but more than 80% of the strains of
      2003 were resistant to tetracycline, co-trimoxazole, and 52% of the same strains
      were resistant to ampicillin. Resistance to chloramphenicol was found in 61%,
      cefuroxime in 56.2%, and cephradine, 52% of the strains. Overall, Shigella
      species showed statistically significant increase in resistance against
      tetracycline, cephradine, trimethoprim/sulfamethoxazole, nalidixic acid, and
      aztreonam (p<0.05) over the 10 years period. This indicates decreased efficacy of
      co-trimoxazole and nalidixic acid for the empirical treatment of shigellosis in
      Sana'a, Yemen. Almost 55.2% of the strains were resistant to 4 drugs. CONCLUSION:
      This is one of the first studies reporting epidemiological pattern of Shigella
      species in Sana'a, Yemen with regard to serotypes and antibiotic resistance
      patterns. Based on these antibiotic resistance pattern findings, it is suggested
      that the commonly in use antibiotics including ampicillin,
      trimethoprim/sulfamethoxazole, tetracycline, and chloramphenicol should not be
      used for empirical treatment of shigellosis in Yemen.

PMID- 16883445
TI  - The relationship between pregnancy induced hypertension and congenital
      thrombophilia.
AB  - OBJECTIVE: To investigate the relationship between some thrombophilic parameters
      and pregnancy induced hypertension (PIH). METHODS: The study took place at the
      Department of Obstetrics and Gynecology, Perinatology Unit, Faculty of Medicine,
      Cukurova University, Turkey, between January 2002 and December 2002. We evaluated
      202 patients. Patients were divided into 2 groups: control group comprised 102
      normotensive patients >20 weeks of pregnancy without any medical or pregnancy
      related pathologies and the study group comprised 100 patients over 20 weeks of
      pregnancy with PIH. These hypertensive patients were divided into 6 sub-groups as
      follows: eclampsia, severe preeclampsia, preeclampsia, chronic hypertension plus
      superimposed preeclampsia, eclampsia, and hemolysis elevated liver enzymes and
      thrombocytopenia (HELLP) syndrome. RESULTS: In all cases, complete blood count,
      antithrombin III, protein S levels, factor V Leiden mutation, prothrombin 20210
      mutation, methylenetetrahydrofolate reductase (MTHFR) 677 mutation and
      homocysteine levels were studied. Statistical analysis of the data was carried
      out using SPSS version 11.0 program. In comparing the 2 groups we used Mann
      Whitney U tests. In comparing the PIH subgroups we used Kruskal-Wallis tests. The
      levels of p<0.05 were accepted as statistically significant. CONCLUSION:
      Antithrombin III deficiency, protein C deficiency, hyperhomocysteinanemia were
      found to be associated with PIH groups. But protein S deficiency, and homozygote
      factor V Leiden mutation, prothrombin 20210, MTHFR 677 mutation were not found to
      be related with PIH.

PMID- 16883447
TI  - Misoprostol for termination of second trimester pregnancy in a scarred uterus.
AB  - OBJECTIVE: To investigate whether Misoprostol for mid-trimester pregnancy
      interruption in women with a scarred uterus has any adverse effects compared with
      those without a scar. METHODS: During 5-year period from 2000-2004 at Queen Alia
      Military Hospital, Royal Medical Services, Amman, Jordan, a consecutive series of
      520 women of 15-28 weeks of gestation who underwent termination of pregnancy were
      studied. Sixty-three patients had undergone at least previous one cesarean
      section and 457 served as control. Termination was undertaken using Misoprostol
      400 ug vaginally as a starting dose followed by 200 ug vaginally every 6 hours,
      complications for each group were recorded. RESULTS: The induction to abortion
      time was not significantly different in both groups (p=0.16); the median dosage
      was almost the same (p=0.31). The rate of incomplete abortion was significantly
      higher in the study group than control 82% versus 60% and 11.5% versus 6.1% for
      bleeding of more than 500 cc, while the rate of other complications was almost
      the same. CONCLUSION: In the second trimester termination of pregnancy, the use
      of Misoprostol in women with previous single or multiple cesarean sections was
      not associated with excess complications.

PMID- 16883446
TI  - Predictors of cesarean section following elective post-dates induction of labor
      in nullipara with uncomplicated singleton vertex pregnancies.
AB  - OBJECTIVE: Although post-dates is among the most common indications for induction
      of labor, no studies have identified the predictors of cesarean section (C/S) in
      that population. The high cesarean rate in our institution for this group of
      women triggered us to assess different induction practices to elicit potential
      causes. METHODS: We conducted a hospital-based retrospective cohort analysis
      using chart reviews of all nullipara women with induced labor at the Children's
      and Women's Health Centre of British Columbia, Vancouver, Canada, during the 2
      year period, April 1998 to March 2000. The C/S rate was compared among 3 groups
      of women who were divided according to their induction method. RESULTS: Three
      hundred and thirty-nine women meeting the inclusion criteria were induced. Of the
      25 women who received oxytocin ideally and the 111 women who did not, 7 (28%) and
      53 (48%) were delivered by C/S, (x2=3.228 p=0.07; relative risks 0.59 [95%
      confidence interval 0.30, 1.13]). A significantly lower C/S rate (x2=21.9,
      p<0.0005) was found among women induced with prostaglandin (PG) alone (19.4%)
      compared with those induced with PG and oxytocin, whether oxytocin was given
      ideally (38.3%) or not ideally (45.4%). Of women who received oxytocin, there was
      no difference in chorioamnionitis (x2=0.485, p=0.49) between those who had an
      early membrane rupture (with or pre-oxytocin, 22.4%) and those who had membrane
      rupture following a period of oxytocin infusion (18.5%). CONCLUSION: The need for
      oxytocin or less than 2 doses of PG is associated with increased risk of C/S.
      Whether oxytocin was given according to protocol (ideally) or not, made no
      difference to the C/S risk in this population.

PMID- 16883448
TI  - Adolescent pregnancy in West Turkey. Cross sectional survey of married
      adolescents.
AB  - OBJECTIVE: The purpose of this research was to determine both the fertility
      characteristics of married adolescent women in Denizli province center and the
      adolescent pregnancy rate and also some factors that could occur with adolescent
      pregnancy. METHODS: This cross-sectional study was conducted in the Denizli
      province center in the year 2001. According to the Turkish Demographic Health
      Survey 1998 statistics, the percentage of married adolescents between 15-19 years
      of age who have begun to give birth is 9.3-10.2%. The sample size of 3471 was
      determined using Epi Info software. To reach this sample size, 5 of the 25 health
      clinics in Denizli province center were chosen by simple random sampling method.
      RESULTS: Approximately 6.4% of the adolescents were married, 4.9% had been
      pregnant as an adolescent, 4.8% had delivered a baby, 23.3% of the married
      adolescents had never been pregnant, 23.3% were pregnant with their first child,
      and 51.2% were mothers; 76.7% had been pregnant one or more times. The majority
      of the married adolescent women in the research group (57.2%) do not use any
      method of family planning, followed by 15.7% who use an intrauterine device. Age,
      lower degree of education (less than 8 years) and unemployment were identified as
      risk factors for adolescent pregnancy. CONCLUSION: The results of this study
      suggest that although the frequency of adolescent pregnancy in the region is
      lower than the mean value in Turkey, it is higher compared with other countries.
      Age, education <8 years and unemployment are risk factors for adolescent
      pregnancy.

PMID- 16883449
TI  - Comparison of underlying lesions in pediatric and adult ovarian torsion.
AB  - OBJECTIVE: To compare the pediatric and adult ovarian torsion and explore a
      quantitative value to predict a possible underlying tumor. METHODS: This study
      included 32 pediatric and 33 adult female cases diagnosed with ovarian torsion
      and underwent surgical treatment in Dr. Behcet Uz Children's Research Hospital
      and Ataturk Education and Research Hospital, Izmir, Turkey between 1989 and 2005.
      We evaluated the properties of the cases statistically. RESULTS: The mean age of
      pediatric was 8 years and 3 months and adult cases was 39 years and 8 months. Six
      cases had an underlying tumor in both pediatric and adult group. The mean
      diameter and volume difference were 6.84 cm, 91 cc in pediatric and 12.69 cm and
      1087 cc in the adult group. In statistical analysis, the diameter and volume
      increase were significantly higher in cases with underlying tumor in pediatric
      group. The cut-off value was 7 cm in diameter and 104 cc in volume increase. In
      the adult group, the diameter and volume increase were not significant in tumor
      positive and negative group. CONCLUSION: Torsion of the ovary requiring surgery,
      is rare and is the mot common reason of abdominal/pelvic mass. These cases are
      often difficult to decide for surgical procedure especially in pediatric cases.
      We conclude that an underlying lesion more commonly occurs in children with an
      increase in ovarian volume of more than 104 cc and a diameter more than 7 cm.
      Great care should be taken for laparoscopic conservative management especially in
      these cases. The quantitative analysis is not predictive for the underlying solid
      lesion in adult cases.

PMID- 16883450
TI  - Recurrence in breast cancer. Analysis with frailty model.
AB  - OBJECTIVE: To determine the value of known prognostic factors for metastasis in
      breast cancer by accounting for patient-specific effect of patients who received
      surgical treatment followed by adjuvant treatment using the frailty model.
      METHODS: One hundred seventeen women with breast cancer who underwent surgery
      followed by adjuvant therapy at 3 hospitals in Tehran, Iran between 1995 and 2003
      were enrolled in this study. Women with defined breast cancer with no distant
      metastases at time of diagnosis that have undergone modified radical mastectomy
      or breast-conserving surgery were enrolled. Tumors were classified according to
      the Tumor, Node, Metastasis (TNM) system of the American Joint Committee on
      cancer. Grading was performed according to Scarff-Bloom-Richardson method.
      Estrogen receptor (ER) was measured by immunohistochemistry method. The patients
      have been followed regularly by routine clinical laboratory profile, serologic
      markers (CEA, CA15-3) and para-clinical examinations; furthermore, we have
      followed missing materials by other access ways such as calling. RESULTS: Median
      follow up time for patients was 26 months after surgery. During the follow up
      time 44 (38%) patients developed metastasis and 20 (45%) of these 44 patients
      experienced the second metastasis. The median disease-free survival for patients
      in the study was 49.6 month. The median time to experience second metastasis
      after the first one was 22.5 months. Risk of occurrence of a metastasis in the
      first year after surgery was 12%. Risk of experience a metastasis up to the
      second year was 32% and up to fifth years was 69%. Result of fitting a frailty
      model to data showed that size of tumor, number of positive lymph nodes and
      histologic grade had a significant effect on the risk of metastasis (p<0.05).
      Patients with tumor size larger than 5 cm were in higher risk of metastasis
      compared with others. Increase in the number of positive lymph nodes to more than
      10, increased risk of metastasis. Patients with moderate or undifferentiated
      histologic grade were in higher risk of metastasis to well differentiated
      patients. Age, family history, lymph node stage, and ER had no significant
      effect. It was found that there was heterogeneity between patients after
      adjusting for other covariates because variance of frailty was 0.315. It means
      that based on the variance of the distribution of frailty, the relative risk of
      high-risk patients to low-risk patients was 7.2, wherein high-risk group is
      defined as a cluster at the 95th percentile and low-risk to a cluster of 5th
      percentile of the frailty distribution. CONCLUSION: Known risk factors describe
      the risk of metastasis partly and other unknown or unmeasured factors, such as
      genetics or environmental factors are important to describe the risk of
      metastasis in breast cancer.

PMID- 16883451
TI  - The effects of dopexamine in bupivacaine and ropivacaine induced cardiotoxicity
      in isolated rat heart.
AB  - OBJECTIVE: To compare the inotropic and chronotropic effects of ropivacaine and
      bupivacaine in an isolated, spontaneously beating rat heart, and to determine the
      reversal effects of dopexamine on these effects. METHODS: The study was conducted
      at the Department of Physiology, Medical Faculty, Osmangazi University,
      Eskisehir, Turkey in November 2001. Fifty animals were randomly assigned to 5
      groups. Hearts were perfused with a modified Krebs Henseleit solution. In group I
      (n=10) hearts were exposed to bupivacaine 5 x 10-6 M and in group II (n=10)
      hearts were exposed to ropivacaine 5 x 10-6 M for 15 minutes. Group III (n=10)
      was the dopexamine control group and hearts were exposed to dopexamine 1 x 10-6 M
      for 5 minutes. In group IV (n=10) and in group V (n=10) hearts were exposed to
      dopexamine in 1 x 10-6 M doses immediately after the bupivacaine and ropivacaine
      infusions. Heart rates and contractile forces were recorded continuously during
      the study. RESULTS: Both of the local anesthetics had cardiac depressant effect
      on isolated hearts. Bupivacaine created more significant effect on heart rate and
      contractility than ropivacaine. Hearts receiving dopexamine after the infusion of
      local anesthetic, recovered more quickly. CONCLUSION: Bupivacaine had more
      depressant effects on cardiac contractility and chronotropy than ropivacaine.
      Dopexamine may provide an alternative to presently recommended pharmacological
      therapy in cases of bupivacaine and ropivacaine induced cardiotoxicity. But, the
      clinical impact of the use of dopexamine in this situation deserves further
      evaluation.

PMID- 16883452
TI  - Comparison of analgesic activity of the addition to neostigmine and fentanyl to
      bupivacaine in postoperative epidural analgesia.
AB  - OBJECTIVE: To compare the analgesic and side effects of bupivacaine in
      combinations with neostigmine and fentanyl using patient-controlled-epidural
      analgesia (PCEA) methods in the postoperative period after abdominal
      hysterectomy. METHODS: Seventy-five adult American Society of Anesthesiologists
      physical status I-II patients, aged 18-65 years were included in the study. The
      study took place in Celal Bayar University Hospital, Turkey between 2003-2004
      years. After preoperative epidural catheterization, the patients were operated
      under general anesthesia. After surgery, the patients were randomly allocated in
      a double-blinded manner to receive PCEA and divided into 3 groups: Group B:
      0.125% bupivacaine, Group N: 0.125% bupivacaine plus neostigmine 4 ug kg-1 and
      Group F: 0.125% bupivacaine plus 1 ug kg-1 fentanyl solutions (10 mL loading
      dose, 5 mL bolus dose, 10 min lockout time, 30 mL in 4 hour limit). During the
      following 24 hours, hemodynamic parameters, pain score using visual analog scale,
      total analgesic consumption, additional analgesic requirements, sedation,
      satisfaction, nausea scores and probable side-effects were evaluated. RESULTS:
      Total analgesic consumption was 143.7 +/- 7.2 mL in Group B, 123.4 +/- 6.2 mL in
      Group N and 106 +/- 8.3 mL in Groups F. The mean value in Group F was
      significantly lower than Group N and Group B (p<0.05), and was lower in Group N
      than Group B. Visual analog scale scores were lower in Group F than other groups
      (p<0.05). There were no differences in side effects between all groups.
      CONCLUSION: Fentanyl and neostigmine by the PCEA method can be used safely for
      postoperative analgesia after gynecologic surgery. They increase analgesia
      quality and satisfaction without an increase in side effects.

PMID- 16883453
TI  - Reliability of vascularized fibula in maintaining arthrodesis following extra
      articular wide excisions of malignant musculoskeletal tumors.
AB  - OBJECTIVE: To evaluate the reliability of vascularized fibula transfer in
      maintaining arthrodesis following wide excision of malignant tumors located at
      the metaphyseal ends of long bones. METHODS: Fourteen patients underwent wide
      extra-articular excisions followed by arthrodesis with vascularized fibula and
      its variants at the Department of Orthopedic Surgery and Traumatology, University
      of Hacettepe Medical School, Ankara, Turkey, in the period from 1996 to 2003.
      There were 9 males and 5 females. Their mean age was 28 years (ranging 12-52
      years). The mean follow-up time was 68 months (range 28-110 months). The most
      common diagnosis was malignant giant cell tumor (6), followed by Ewing's sarcoma
      (3), hemangioendothelioma (2), osteosarcoma (2) and chondrosarcoma (1). Three
      tumors were located at the distal end of the radius, 4 at the proximal humerus, 3
      at the distal femur, one at the proximal tibia, one in distal tibia, one in
      distal humerus and one in proximal ulna. We used fibula as a vascularized graft
      in 4 patients; fibula osteoseptocutaneous flap in 4 cases; bilateral vascularized
      fibulae in 3; fibula with autoclaved autograft in 4 and free osteoseptocutaneous
      fibula in conjunction with a structural allograft and a circular external fixator
      in one patient. RESULTS: In 4 cases, implant failure developed and revision was
      required in 3. One case had local infection around the distal interlocking screw.
      In one case, clawing of first and second toes were developed at the donor side.
      Two patients with metastatic Ewing's sarcoma had metastatic disease. We achieved
      union within 9 months in 12 cases. In 2 cases with implant failure, bony
      consolidations were maintained at 11th and 13th months. CONCLUSION: Vascularized
      fibula transfer is reliable to achieve arthrodesis following extra-articular
      excision of malignant tumors from the metaphyseal ends.

PMID- 16883454
TI  - Assessment of quality of life in children after successful treatment of hip
      dysplasia as compared with normal controls.
AB  - OBJECTIVE: To document the quality of life of children who have been treated for
      developmental dysplasia of the hip (DDH) within the first 3 years of life
      successfully after a minimum follow-up period of 2 years, and compare their
      results with healthy age-matched children. METHODS: Thirty patients with DDH
      treated between 1998 and 2002 in Ankara Numune Education and Research Hospital,
      Ankara, Turkey and 19 age-matched healthy controls were included in this study
      with the approval of the ethical committee. The mean follow up period was 56.1
      months. Each child's parents answered the Child Health Questionnaire-Parent Form
      50 (CHQ-PF50) after giving informed consent. The answers were evaluated, and
      scores were calculated and results were analyzed. RESULTS: There were no
      significant differences in 14 health-related quality of life concepts, according
      to the CHQ instrument's outcomes, between the healthy controls and the patients
      with DDH who were successfully treated within the first 3 years of life. Only the
      physical functioning concept was found to be lower for the DDH patients (Mann
      Whitney U test, p=0.036). CONCLUSION: Although children who were successfully
      treated for DDH may have impairment in physical functioning after a certain
      period of follow-up, there was no significant impairment in physical and
      psychosocial summary scores, in comparison with their age-matched controls.

PMID- 16883455
TI  - A retrospective study of peritonsillar abscess in Riyadh Medical Complex
      [corrected].
AB  - OBJECTIVE: To investigate and study the management pattern of peritonsillar
      abscess, the male to female ratio and incidence. Also, to evaluate the causative
      organism isolated from abscess and reported by culture/sensitivity (C/S).
      METHODS: This study has been designed as a single centered retrospective hospital
      based study. We carried out this study in the Department of ENT, Riyadh Medical
      Complex, Saudi Arabia from 2000 to 2004. We gathered the data via survey (5
      years). There were 81 patients admitted for the management of peritonsillar
      abscess. RESULTS: Mean age of patients was 22 years (range 10 to 60 years; 44
      male, 37 female). The hospital stay varies from 1-8 days with a mean of 4 days.
      The left side is more involved. Treatment consisted mainly incision/drainage
      under local anesthetic in 47 patients (58%), while 5 cases (6%) were carried out
      under general anesthetic. Aspiration and conservative treatment was noted in 25
      (31%) cases, abscess tonsillectomy was carried out in 3 (4%) cases. The most
      common microorganisms isolated from C/S is Group A beta hemolytic streptococcus
      (17/81 [21%]). Penicillin G + Flagyl (49/81 [60%]) were the most common
      antibiotics used. No case of bilateral peritonsillar abscess was found and there
      is no consensus regarding the best technique. Options include needle aspiration,
      incision and drainage and immediate tonsillectomy. CONCLUSION: Peritonsillar
      abscess remain one of the acute admission in the Department of Otolaryngology at
      Riyadh Medical Complex, Riyadh. Incision/drainage remains the gold standard
      treatment, Penicillin G + Flagyl combinations are the cornerstones.

PMID- 16883456
TI  - Intentional sun exposure in infancy in Sakarya, Turkey.
AB  - OBJECTIVE: To determine the extent of intentional sun exposure in infancy, and
      the prevalence of maternal belief that potentially increases the children's harm
      risk from ultraviolet radiation. The major determinants of mothers' beliefs and
      behaviors regarding sunning were also assessed. METHODS: Three hundred and ninety
      six Caucasian women mothering 0-12 month old infants, attending to Sakarya State
      Hospital Healthy Infant outpatient clinic in November 2003, filled in the
      questionnaire after giving their informed consent. Each mother was asked 11
      structured questions regarding maternal education, beliefs regarding benefits or
      harms of sun exposure, use of sunlight for therapeutic purposes, use of sun
      protection, and source of knowledge. RESULTS: The mean age of the mothers was
      27.37 +/- 5.36 years and the children was 5.71 +/- 3.53 months. Two hundred and
      thirty-five mothers (64.1%) believed that sunlight is harmful, but 296 (79.7%)
      named one benefit of intentional baby sunning. Sun causes cutaneous diseases was
      the most frequently (n=83/126) mentioned harm and sun strengthens bones and teeth
      was the number one (n=250/296) benefit according to the mothers. The leading
      source of knowledge for the beneficial effects of the sun was health care
      professionals (physician, midwife, nurse) 45.7% (130/284). There was no
      significant correlation between mothers' sunning behavior and age, education
      level, being advised so by a health care professional or believing that the sun
      was harmful. CONCLUSION: As these results display being the leading source of
      knowledge and initiative of healthy/risky behaviors, primary health care
      physicians/workers have to be informed regarding the vitamin D supplementation
      and risks of sun exposure.

PMID- 16883458
TI  - Granuloma of the appendiceal stump. An unusual cause of right hemicolectomy.
AB  - Granuloma of the appendiceal stump is not a common surgical entity. However,
      hemorrhage which may lead to right hemicolectomy is rare in fact. We report this
      case, in order to avoid this kind of overtherapy.

PMID- 16883457
TI  - Hyperfunctioning intrathyroidal parathyroid carcinoma.
AB  - Intrathyroidal parathyroid carcinoma is an exceedingly rare cause of primary
      hyperparathyroidism with difficulties in the diagnosis and management. We report
      a case of hypercalcemia from intrathyroidal parathyroid carcinoma in a 63-year
      old Saudi female. She was diagnosed 2 years earlier with osteoporosis in a
      primary care clinic and was on alendronate since then. This year she was noted to
      have hypercalcemia, but in retrospect she had more than 10 years history of
      multiple medical problems related to hypercalcemia. Parathyroid 99mTc-SestaMIBI
      scintigraphy revealed parathyroid adenoma in the left inferior parathyroid gland.
      She had successful video-assisted parathyroidectomy that relieved most of her
      symptoms. The extreme rarity of such a case, the interesting clinical
      presentation and review of the literature are discussed.

PMID- 16883459
TI  - Numerical variation of the celiac trunk and anatomical variation in origin and
      course of the dorsal pancreatic artery.
AB  - A numerical anomaly of the celiac trunk and anatomical variation in origin, and
      course of the dorsal pancreatic artery were encountered during a routine upper
      abdomen dissection of a 62-year-old male cadaver. The aim of this study was to
      describe a rare celiac trunk and dorsal pancreatic artery variation in detail,
      which can be a guide and precaution during operative procedures in this region.
      The abdominal aorta, its branches and the pancreas were cut and removed just
      above the celiac trunk and below the superior mesenteric artery to investigate
      the vascular distribution of the pancreas in detail. The celiac trunk divided
      into the left gastric, hepatic, splenic, and dorsal pancreatic arteries. The
      anatomical variation of the celiac trunk and splenic artery makes it vulnerable
      to iatrogenic surgery. Knowledge of the existing aberrations is important in
      planning and conducting surgical procedures.

PMID- 16883461
TI  - Twisted mixed germ cell tumor of the ovary in a child.
AB  - We report an 8-year-old female patient with a mixed germ cell stromal tumor MGCT
      of the left ovary. Exploration revealed that the tumor had been twisted around
      its pedicle. These ovarian tumors are classified among interesting type of tumors
      due to the variability of neoplastic tissues in the same tumor mass, in the
      twisted ovarian tumor. Four histological types of tumor tissues were found: well
      differentiated adenocarcinoma, dysgerminoma, immature teratoma, and focus of
      papillary serous cyst adenoma as well. During our review of the literature, this
      reported case of MGCT of the ovary was among the extremely rare cases, which had
      been reported. Mixed germ cell tumor is well documented in the literature since
      1950.

PMID- 16883460
TI  - Could imatinib replace surgery in esophageal gastrointestinal stromal tumor.
AB  - Gastrointestinal stromal tumors GISTs are cellular spindle, or epithelioid tumors
      that occur in the stomach, intestine, and rarely in the esophagus. A 61-year-old
      man was complaining of resistant dry cough with dysphagia for one month duration.
      Upper gastrointestinal tract endoscopic examination showed a polypoid mass 30 cm
      from the incisors obstructing 50% of the lumen, where multiple biopsies were
      taken. Magnetic resonance imaging MRI showed a mass in the wall of the esophagus
      extending into the thoracic cavity. Histologically, the stained sections with the
      routine hematoxylin and eosin as well as the immunohistochemical stains for
      CD117, CD34, S100, vimentin, and smooth muscle actin confirmed the diagnosis of
      esophageal GIST. The patient was treated with imatinib, 400 mg/day. There was a
      dramatic reduction in the size of the tumor with successful improvement of his
      symptoms after 2 months of treatment, which was confirmed by repeated upper GIT
      endoscopy, and MRI.

PMID- 16883462
TI  - Successful use of non-invasive positive pressure ventilation in a complicated
      flail chest.
AB  - The current advanced trauma life support manual states that patients with
      significant hypoxia namely, SaO2 <90% on room air as a result of pulmonary
      contusion should be intubated and ventilated within the first hour of injury.
      Recently, several researchers have shown improved outcomes when patients with
      acute respiratory failure are managed with non-invasive positive pressure
      ventilation NIPPV. Trauma patients may also benefit from this therapy. We report
      a case of 15-year-old boy with isolated flail chest and pulmonary contusion, who
      was intubated in the emergency room, and was managed successfully with the NIPPV
      in the intensive care unit ICU despite, having had aspiration pneumonia early in
      the course of his stay. After initial stabilization, he failed a spontaneous
      breathing trial. Due to absence of contraindications to the use of NIPPV, the
      patient was extubated on day 7 from pressure support ventilation of 15 cmH2O and
      positive end expiratory pressure of 8 cmH2O to immediate NIPPV use. Three days
      later after a total of 50 hours of NIPPV use in the ICU the patient was
      successfully discharged home.

PMID- 16883463
TI  - Giant cell tumor of the rib.

PMID- 16883464
TI  - Intranodal palisaded myofibroblastoma with metaplastic bone formation.

PMID- 16883465
TI  - Successful coronary artery bypass grafting in a patient with aplastic anemia and
      Sjogren syndrome.

PMID- 16883466
TI  - Ensuring the quality of peer-review process.

PMID- 16883467
TI  - Comparison of SPO2, hearth rate and body temperature values in abdominal
      compartment syndrome in a rat model with intraabdominal sepsis and intraabdominal
      hypertension.

PMID- 16883468
TI  - Effects of different bolus doses of remifentanil on laryngeal mask airway
      insertion during day-case surgery.

PMID- 16883469
TI  - Can incision barrier decrease the risk of surgical site infection after
      appendectomy?

PMID- 16883470
TI  - Diagnostic value of bilirubin concentrations compared with novel and traditional
      biomarkers in atherosclerosis with coronary artery disease.

PMID- 16883471
TI  - Congenital factor X deficiency of coagulation revealed by epistaxis.

PMID- 16883472
TI  - Effects of erythropoietin on fracture healing in rats.

PMID- 16883473
TI  - Effects of moderate alcohol consumption on serum marker enzymes of rabbits.

PMID- 16883474
TI  - A study on children and adolescents with disabilities in Kahramanmaras, Turkey.

PMID- 16883475
TI  - Brucella seropositivity in South and Southeast Turkey.

PMID- 16883476
TI  - Epidemiology of travel-related malaria in a non-malarious area of Saudi Arabia.

PMID- 16883477
TI  - Correlated expression of gfp and Bt cry1Ac gene facilitates quantification of
      transgenic hybridization between Brassicas.
AB  - Gene flow from transgenic oilseed rape (BRASSICA NAPUS) might not be avoidable,
      thus, it is important to detect and quantify hybridization events with its
      relatives in real time. Data are presented showing the correlation between
      genetically linked green fluorescent protein (GFP) with BACILLUS THURINGIENSIS
      (Bt) CRY1AC gene expression in hybrids formed between transgenic B. NAPUS
      "Westar" and a wild Chinese accession of wild mustard (B. JUNCEA) and
      hybridization between transgenic B. NAPUS and a conspecific Chinese landrace
      oilseed rape. Hybrids were obtained either by spontaneous hybridization in the
      field or by hand-crossing in a greenhouse. In all cases, transgenic hybrids were
      selected by GFP fluorescence among seedlings originating from seeds harvested
      from B. JUNCEA and the Chinese oilseed rape plants. Transgenicity was confirmed
      by PCR detection of transgenes. GFP fluorescence was easily and rapidly detected
      in the hybrids under greenhouse and field conditions. Results showed that both
      GFP fluorescence and Bt protein synthesis decreased as either plant or leaf aged,
      and GFP fluorescence intensity was closely correlated with Bt protein
      concentration during the entire vegetative lifetime in hybrids. These findings
      allow the use of GFP fluorescence as an accurate tool to detect gene-flow in time
      in the field and to conveniently estimate BT CRY1AC expression in hybrids on-the
      plant.

PMID- 16883478
TI  - Evidence for inbreeding depression in the food-deceptive colour-dimorphic orchid
      Dactylorhiza sambucina (L.) Soo.
AB  - About one third of all orchid species are deceptive, i.e., not providing any
      reward to their pollinator. Such species often have lower visitation rates
      compared to rewarding relatives. This could result in lower levels of
      geitonogamous selfing and thus would provide an advantage in term of progeny
      fitness through inbreeding avoidance. This hypothesis could be tested by
      comparing the level of inbreeding depression between deceptive and rewarding
      orchids. However, due to the difficulty to raise orchids from seeds, few studies
      of inbreeding depression are available, and most are focused on very early life
      stages, such as seed mass or embryo viability. Here, we present the results from
      an experimental investigation of inbreeding depression in the deceptive flower
      colour dimorphic Dactylorhiza sambucina, from in vitro cultivation to greenhouse
      soil transplantation. We found strong inbreeding depression at all recorded
      stages (i.e., germination and survival), with estimates ranging from 0.47 to
      0.75. Our study finally proposes a simple and suitable experimental protocol to
      raise orchids from seeds with high germination rates.

PMID- 16883479
TI  - Redox regulation and flower development: a novel function for glutaredoxins.
AB  - Glutaredoxins (GRXs) are small, ubiquitous oxidoreductases that have been
      intensively studied in E. COLI, yeast and humans. They are involved in a large
      variety of cellular processes and exert a crucial function in the response to
      oxidative stress. GRXs can reduce disulfides by way of conserved cysteines,
      located in conserved active site motifs. As in E. COLI, yeast, and humans, GRXs
      with active sites of the CPYC and CGFS type are also found in lower and higher
      plants, however, little has been known about their function. Surprisingly, 21
      GRXs from ARABIDOPSIS THALIANA contain a novel, plant-specific CC type motif.
      Lately, information on the function of CC type GRXs and redox regulation, in
      general, is accumulating. This review focuses on recent findings indicating that
      GRXs, glutathione and redox regulation, in general, seem to be involved in
      different processes of development, so far, namely in the formation of the
      flower. Recent advances in EST and genome sequencing projects allowed searching
      for the presence of the three different types of the GRX subclasses in other
      evolutionary informative plant species. A comparison of the GRX subclass
      composition from PHYSCOMITRELLA, PINUS, ORYZA, POPULUS, and ARABIDOPSIS is
      presented. This analysis revealed that only two CC type GRXs exist in the
      bryophyte PHYSCOMITRELLA and that the CC type GRXs group expanded during the
      evolution of land plants. The existence of a large CC type subclass in
      angiosperms supports the assumption that their capability to modify target
      protein activity posttranslationally has been integrated into crucial plant
      specific processes involved in higher plant development.

PMID- 16883480
TI  - Effects of cytokinin production under two SAG promoters on senescence and
      development of tomato plants.
AB  - Two promoters of senescence-associated ARABIDOPSIS genes, SAG12 and SAG13, were
      used in tomato plants to express IPT that catalyzes the rate-limiting step in
      cytokinin biosynthesis. Expression of these heterologous promoters in tomato
      plants was analyzed using the reporter gene beta-glucuronidase. Both promoters
      are expressed in tomato leaves in a manner similar to their expression in
      ARABIDOPSIS plants. The SAG12 promoter is very specific to senescing leaves,
      whereas the SAG13 promoter is expressed in mature leaves prior to the onset of
      visible senescence and its expression increases in senescing leaves. Expression
      of both promoters in tomato tissues other than leaves was very low . IPT
      expressed under the control of SAG12 and SAG13 promoters ( PSAG12::IPT and
      PSAG13::IPT, respectively) resulted in suppression of leaf senescence and
      advanced flowering, as well as in a slight increase in fruit weight and fruit
      total soluble solids (TSS). However, expression of PSAG13::IPT also led to stem
      thickening, short internodal distances and loss of apical dominance. In contrast
      to the autoregulation of PSAG12::IPT, PSAG13::IPT is expressed at higher levels
      in mature leaves. This difference is likely due to PSAG13::IPT exhibiting two
      phases of expression - a senescence-independent expression prior to the onset of
      senescence that is not subjected to autoregulation by cytokinin, and enhanced
      expression throughout senescence which is autoregualted by cytokinin. This
      moderate different autoregulated behavior of PSAG12::IPT and PSAG13::IPT markedly
      influenced plant development, emphasizing the biological effects of cytokinin in
      addition to senescence inhibition.

PMID- 16883481
TI  - Cadmium induces changes in sucrose partitioning, invertase activities, and
      membrane functionality in roots of Rangpur lime (Citrus limonia L. Osbeck).
AB  - Cadmium (Cd) uptake effects on sucrose content, invertase activities, and plasma
      membrane functionality were investigated in Rangpur lime roots ( CITRUS LIMONIA
      L. Osbeck). Cadmium accumulation was significant in roots but not in shoots and
      leaves. Cadmium produced significant reduction in roots DW and increment in WC.
      Leaves and shoots did not show significant differences on both parameters.
      Sucrose content was higher in control roots than in Cd-exposed ones. Apoplastic
      sucrose content was much higher in Cd-exposed roots than in control ones. Cd
      exposed roots showed a significant decrease in both cell wall-bound and
      cytoplasmic (neutral) invertase activities; while the vacuolar isoform did not
      show any change. Alterations in lipid composition and membrane fluidity of Cd
      exposed roots were also observed. In Cd-exposed roots phospholipid and glycolipid
      contents decreased about 50 %, while sterols content was reduced about 22 %.
      Proton extrusion was inhibited by Cd. Lipid peroxidation and proton extrusion
      inhibition were also detected by histochemical analysis. This work's findings
      demonstrate that Cd affects sucrose partitioning and invertase activities in
      apoplastic and symplastic regions in Rangpur lime roots as well as the plasma
      membrane functionality and H (+)-ATPase activity.

PMID- 16883482
TI  - Non-structural carbohydrates and nitrogen dynamics in mediterranean sub-shrubs:
      an analysis of the functional role of overwintering leaves.
AB  - Previous studies have led to contrasting results about the role of overwintering
      leaves as storage sites, which is related to leaf longevity and life-form. The
      aim of this study was to evaluate the functional role of the leaves of four
      species of Mediterranean sub-shrubs, with different leaf phenology, as sources of
      nitrogen (N) and non-structural carbohydrates (NSC) for shoot growth. The
      seasonal dynamics of the concentrations and pools of N and NSC were assessed
      monthly in the leaves and woody organs of each species. Overwintering and spring
      leaves served as N and NSC sources for shoot growth in the evergreen species
      analyzed, providing up to 73 % and 324 % of the N demand for spring and autumn
      growth, respectively. Excess autumn N was stored in woody structures which
      contributed to the N and NSC requirements of spring growth. In the winter
      deciduous species, woody organs were the main N source for spring growth, while
      current photosynthesis from immature brachyblasts seemed to be the main carbon
      (C) source. Due to their short lifespan, overwintering and spring leaves did not
      show several translocation processes throughout their life time, their
      contribution to new growth being made during senescence. The successive exchange
      of leaf cohorts displayed by Mediterranean sub-shrubs might serve as a mechanism
      to recycle N and C between consecutive cohorts as plants perform the pheno
      morphological changes needed to adapt their morphology to the seasonality of
      their environment.

PMID- 16883483
TI  - Nectar resorption and translocation in Cucurbita pepo L. and Platanthera
      chlorantha Custer (Rchb.).
AB  - Nectar resorption and sugar translocation were studied in Cucurbita pepo
      (Cucurbitaceae) and Platanthera chlorantha (Orchidaceae) by micro
      autoradiography. In both species, nectar was resorbed in pollinated and
      unpollinated flowers and ovules developing into seeds were found to be the main
      sugar sink. In C. pepo, the mobility of resorbed sugars in pollinated female
      flowers was higher than in unpollinated ones; male flowers showed lower mobility
      of resorbed sugar. In P. chlorantha, radioactivity was detected in pollinated
      flowers below and above labelled unpollinated ones: the nearer the flower, the
      stronger the accumulation of label in developing fruits.

PMID- 16883484
TI  - Diversification of CYCLOIDEA-like TCP genes in the basal eudicot families
      Fumariaceae and Papaveraceae s.str.
AB  - CYCLOIDEA-like genes belong to the TCP family of transcriptional regulators and
      have been shown to control different aspects of shoot development in various
      angiosperm lineages, including flower monosymmetry in asterids and axillary
      meristem growth in monocots. Genes related to the CYC gene from ANTIRRHINUM show
      independent duplications in both asterids and rosids. However, it remains unclear
      to what extent this affected the evolution of flower symmetry and shoot branching
      in these and other eudicot lineages. Here, we show that CYC-like genes have also
      undergone duplications in two related Ranunculales families, Fumariaceae and
      Papaveraceae s.str. These families exhibit morphological diversity in flower
      symmetry and inflorescence architecture that is potentially related to functions
      of CYC-like genes. We present sequences of 14 CYC-related genes covering 9
      genera. Phylogenetic analyses indicate the presence of three clades of CYC-like
      genes. Shared motifs in the region between the TCP and R domains of CYC-like
      genes between Fumariaceae, Papaveraceae s.str., and AQUILEGIA (Ranunculaceae)
      indicate that the observed duplications originated from a single CYC gene present
      in all Ranunculales. RT-PCR expression data suggest that gene duplication and
      diversification in Fumariaceae and Papaveraceae s.str. was accompanied by
      divergence in expression patterns.

PMID- 16883485
TI  - Circumvention of over-excitation of PSII by maintaining electron transport rate
      in leaves of four cotton genotypes developed under long-term drought.
AB  - We investigated the patterns of response to a long-term drought in the field in
      cotton cultivars (genotypes) with known differences in their drought tolerance.
      Four cotton genotypes with varying physiological and morphological traits, suited
      to different cropping conditions, were grown in the field and subjected to a long
      term moderate drought. In general, cotton leaves developed under drought had
      significantly higher area-based leaf nitrogen content (N (area)) than those under
      well irrigation. Droughted plants showed a lower light-saturated net
      photosynthetic rate (A (sat)) with lower stomatal conductance (g (s)) and
      intercellular CO (2) concentration (C (i)) than irrigated ones. Based on the
      responses of A (sat) to g (s) and C (i), there was no decreasing trend in A (sat)
      at a given g (s) and C (i) in droughted leaves, suggesting that the decline in A
      (sat) in field-grown cotton plants under a long-term drought can be attributed
      mainly to stomatal closure, but not to nonstomatal limitations. There was little
      evidence of an increase in thermal energy dissipation as indicated by the lack of
      a decrease in the photochemical efficiency of open PSII (F (v)'/F (m)') in
      droughted plants. On the basis of electron transport (ETR) and photochemical
      quenching (q (P)), however, we found evidence indicating that droughted cotton
      plants can circumvent the risk of excessive excitation energy in photosystem (PS)
      II by maintaining higher electron transport rates associated with higher N
      (area), even while photosynthetic rates were reduced by stomatal closure.

PMID- 16883487
TI  - Construction of a primary RH panel of Italian ryegrass genome via UV-induced
      protoplast fusion.
AB  - Symmetric and asymmetric somatic hybrids were produced via protoplast fusion
      between common wheat ( TRITICUM AESTIVUM L.) cv. "Jinan 177" and Italian ryegrass
      ( LOLIUM MULTIFLORUM Lam.). The ryegrass without or with UV irradiation was used
      as a donor, providing a small amount of chromatin. In these somatic hybrids, most
      ryegrass chromosomes have been confirmed preferential elimination and the somatic
      hybrid calli and plants showed wheat-like morphology. Some of the hybrid lines
      were used for the analysis of distribution and heredity of donor DNA in the
      hybrid genome and the possibility of establishing a radiation hybrid (RH) panel
      of the ryegrass in the present experiment. These hybrids, subcultured for two and
      three years, retained the ryegrass DNA examined by RFLP and GISH analysis,
      respectively. Distribution of the ryegrass DNA in the wheat genomes of 20 single
      cell individuals, randomly selected from hybrid cell lines produced, were
      analyzed by 21 ryegrass genome specific SSR markers. The average frequencies of
      molecular marker retention in symmetric hybrid lines (UV 0), as well as
      asymmetric hybrid lines from UV 30 s and 1 min were 10.88, 15.48 and 33.86,
      respectively. It was suggested that the UV dose increased the introgression of
      donor DNA into wheat genome. The ryegrass SSR fragments in most asymmetric hybrid
      cell lines remained stable over a period of 2 approximately 3 years. This
      revealed that those asymmetric somatic hybrids are suitable for the introgression
      of ryegrass DNA into wheat, and for RH panel and RH mapping.

PMID- 16883486
TI  - 13C labelling reveals different contributions of photoassimilates from
      infructescences for fruiting in two temperate forest tree species.
AB  - The pathways of currently fixed carbon in fruit bearing branchlets were
      investigated in two temperate forest tree species (CARPINUS BETULUS and FAGUS
      SYLVATICA), which differ in texture of their vegetative infructescence tissues
      (leaf-like in CARPINUS vs. woody in FAGUS). During late spring, (13)C pulse
      labelling was conducted on girdled, defoliated, girdled plus defoliated and
      untreated fruiting branchlets of mature trees IN SITU, to assess changes in C
      relations in response to the introduced C source-sink imbalances. At harvest in
      early August, 75 - 100 % of the recovered (13)C label was bound to
      infructescences (either fruits or vegetative infructescence tissue), revealing
      them as the prime C sinks for current photoassimilates. Leaves on girdled
      branchlets were not stronger labelled than on ungirdled ones in both species,
      indicating no upregulation of the leaves' photosynthetic capacity in response to
      the prevention of phloemic transport, which was also supported by measurements of
      light saturated photosynthesis. In contrast, (13)C labels tended to be higher
      after complete defoliation in the vegetative infructescence tissues of CARPINUS,
      suggesting enhanced net photosynthesis of green infructescence parts as
      compensation for the loss of regular leaves. The total labelling-derived (13)C
      content of whole infructescences was very similar between foliated and defoliated
      CARPINUS branchlets. Cupulae of FAGUS, on the other hand, remained almost
      unlabelled on defoliated branchlets, indicating the photosynthetic inactivity of
      this woody infructescence tissue. Consequently, CARPINUS still produced
      relatively high fruit masses on girdled plus defoliated branchlets, while in
      FAGUS fruit development ceased almost completely at this most severe treatment.
      Our results highlight that green vegetative infructescence tissue assimilates
      substantial amounts of C and can partly substitute regular leaves as C sources
      for successful fruit development.

PMID- 16883490
TI  - [Collagen injection for augmentation of periprosthetic leakage after tracheo
      esophageal voice restoration].
AB  - After laryngectomy the majority of patients receive a vocal rehabilitation by
      tracheo-esophageal puncture and insertion of voice prosthesis. Periprosthetic
      leakage causing aspiration represents a well known complication and is frequently
      treated by temporary removal of the prosthesis with shrinkage of the shunt. Here
      we describe 10 patients with such a leakage treated by collagen injection for
      periprosthetic tissue augmentation. A mean of 1,6 injections were necessary for
      complete control of the leakage. The injection was well tolerated and was found
      effective for median period of 9,3 months. In our hands the periprosthetic
      collagen injection represents an effective and well tolerated procedure for
      temporary augmentation of tracheo-esophageal leakage in post-laryngectomy
      patients. However, alternative fillers without pre-testing necessity and longer
      augmentation intervals should be considered.

PMID- 16883492
TI  - [Joint statement on the need for preoperative coagulation tests before adenotomy
      and tonsillectomy in children].

PMID- 16883495
TI  - [Diagnosis and therapy of epistaxis].
AB  - Epistaxis is one of the most frequent emergencies in Otorhinolaryngology and
      occurs in other disciplines, esp. in Oncology, Traumatology and Pediatrics as
      well. Even the young otorhinolaryngologist should be basically informed about the
      diagnostic concepts and therapies available for nosebleeding patients. The
      specialist should be capable to choose between modern and traditional
      therapeutical options in order to realise a definitive closure of the bleeding
      source with maximal comfort for the patient and with preservation of functionally
      important structures. However, even for the specialized rhinologist it can be
      difficult to overview the tremendous variety of the different therapies and
      diagnostical procedures. This article is a compressed review of both the
      traditional guidelines and the more innovative methods concerning epistaxis.
      Additionally it deals with the vascular anatomy of the nose and the
      pathophysiology of epistaxis.

PMID- 16883494
TI  - [Distant metastases on acinic cell carcinoma of the parotid gland after 12 years
      symptom-free interval].
AB  - Acinic cell carcinoma of parotid gland as cause of distant metastases are rare.
      The patient was a 60-year-old woman who had in 1993 a acinic cell carcinoma of
      right parotid gland. Tumour can be resected through total parotidectomy with
      facial nerve anastomosis and modified radical neck dissection (T (3) N (2b) M
      (0)). Since the operation the patient has remained symptom-free without any sign
      of tumour recurrence. After 12 years the patient noted swelling in the region of
      sternum and biopsy was necessary. Histologically and immunohistochemically the
      diagnosis of distant metastase on acinic carcinoma of the parotid gland was
      confirmed.

PMID- 16883493
TI  - [Neurilemmoma of the head and neck--report of 3 cases].
AB  - BACKGROUND: Neurilemmoma are benign tumors of the nerve-sheath, also known as
      schwannoma. Beside intracranial manifestation, neurilemmoma are found at other
      peripheral nerves of the head and neck. CASE REPORT: We present three cases of
      patients with seldom manifestation of neurilemmoma of the supraglottis, the
      retropharyngeal space and a neurilemmoma of the hypoglossal nerve. The
      histological examination showed two types of Antoni-A-neurilemmoma, whereas one
      tumor was found with mixed type A and B-neurilemmoma. CONCLUSION: Although
      extracranial neurilemmoma of retropharygeal space, neck or supraglottic larynx
      are rare tumors, neurilemmoma should be involved in differential diagnosis of
      tumors in these areas. The therapy of choice consists of complete surgical
      removal and histological examination.

PMID- 16883497
TI  - [Herbert Hohler--a pioneer of aesthetic surgery in Germany].

PMID- 16883498
TI  - [The application of endoscopy in aesthetic breast surgery].
AB  - During the last decades, numerous surgical techniques have been described for
      breast augmentation. In addition to the very popular inframammary and the
      periareolar approaches, the transaxillary technique provides an elegant means of
      conducting a safe and accurate implant placement without producing visible scars
      on the breast mound. Due to a questionable lack of intraoperative visualisation
      with resultant higher complication rates,we conducted a retrospective analysis
      comparing the endoscopy-assisted transaxillary approach with the inframammary
      technique. A retrospective analysis was conducted comparing the endoscopy
      assisted transaxillary approach with the more commonly chosen inframammary
      aditus. Patients undergoing breast augmentation from 1997 to 2005 were analysed
      retrospectively. The analysis was conducted in patients undergoing this procedure
      for aesthetic reasons only. Underlying breast pathology as well as previously
      performed breast surgery were among the exclusion criteria. The Client
      Satisfaction Questionnaire (CSQ-8) was applied for assessment of patient
      satisfaction. From 1997 to 2005, 96 patients underwent breast augmentation at our
      institution. Implant volumes ranged from 150 to 400 ml.62.5% preferred the
      transaxillary technique vs. 37.5% who chose the inframammary route. Complication
      rates were low in both patient subsets, the statistics revealing no differences.
      Assessment of patient satisfaction displayed high levels of satisfaction in both
      groups without any significant differences. The endoscopy-assisted transaxillary
      breast augmentation is a safe technique which generates high levels of patient
      satisfaction. Predictable results can be achieved by this approach which is
      preferred by the majority of patients when offered.

PMID- 16883499
TI  - [Chiparray-based identification of gene expression in HUVECs treated with low
      frequency electric fields].
AB  - PURPOSE: After high-voltage electric injury, patients often show progressive
      tissue necrosis and thrombosis of blood vessels even remote from the entry and
      exit sites of electrical current. Recently, we were able to demonstrate IN VIVO
      and VITRO the release of several prothrombotic factors. In this study, we report
      on IN VITRO studies performed to characterize gene expression profiles using a
      DNA-microarray in HUVECs (human umbilical vein endothelial cells) exposed to low
      frequency electrical current. METHODS: HUVECs were plated and grown to confluence
      in a culture chamber. They were exposed to 25 periods of 50 Hz sinusoidal waves.
      The periods had field strength of 60 V/cm and duration of 100 ms. Periods were
      interrupted by 10-second intervals to prevent significant joule heating. Control
      HUVECs were treated identically except that no electric field was applied.
      Samples from control and treated cells were taken after six and 24 hours. A PIQOR
      Immunology Array (Milteny Biotech) containing 1076 cDNAs was used for gene
      expression analysis. Hybridization of Cy3- and Cy5-labelled samples, image
      capture, and signal quantification of hybridized arrays were performed. Local
      background was subtracted from the signal to obtain the net signal intensity and
      the ratio of Cy5/Cy3. The ratios were normalized to the median of all ratios and
      the mean of the ratios of four corresponding spots was computed. More than two
      fold increases or decreases of the gene expression were regarded as relevant.
      RESULTS: A total of 413 genes (1s + s) respectively 345 genes (2s + s) could be
      detected. The results obtained display a distinct expression pattern of up
      regulated genes known to be important for hemostasis (e.g. UPA, UPAR, ECE1,
      PAFAH1B1, PGT, INOS, ENOS, TPA, ICAM1, VCAM1, PAI1, PAI2, VWF, PTGDR, F3, THBD),
      which was most evident after 24 hours. This expression profile might lead to a
      hypercoagulated state. Furthermore, the expression of genes involved in
      angiogenesis was reduced whereas the expression of those involved in platelet
      formation was increased. CONCLUSION: Our results indicate that low frequency
      electrical fields induce a distinct signature of differential gene expression in
      exposed HUVECs. This might explain the clinical observation of thrombosis and
      progressive tissue necrosis after electrical injury.

PMID- 16883500
TI  - [Current treatment strategies for paediatric burns].
AB  - Paediatric burns occupy the third place in the severe accident statistics in
      Germany after traffic injuries and drowning. The paper reviews current treatment
      concepts of pre-hospital management, fluid resuscitation and surgical therapy in
      paediatric burned patients. Specific features in the approximation of the total
      body surface area burn and indications for transfer of paediatric burn victims to
      specialized units are discussed. The therapy of severe paediatric burns requires
      an interdisciplinary team consisting of especially skilled plastic or paediatric
      surgeons,anaesthetists, psychiatrists or psychologists, specifically trained
      nurses, physiotherapists and social workers. The rehabilitation process starts
      basically with admission to the burn unit. A tight cooperation between therapists
      and the relatives of the paediatric burn victim is needed for psychological
      recovery and reintegration into society.'The adaptation to the suffered trauma
      resulting in life-long disability and disfigurement is the main task of
      psychotherapy.

PMID- 16883501
TI  - [Memantine and Complex Regional Pain Syndrome (CRPS): effects of treatment and
      cortical reorganisation].
AB  - BACKGROUND: In recent studies a central nervous system involvement in the
      pathogenesis of Complex Regional Pain Syndrome (CRPS) was suggested, stimulating
      the introduction of central acting drugs. Animal studies have demonstrated an
      increased expression of the N-methyl-D-aspartate (NMDA) receptors in experimental
      neuropathic pain. PURPOSE: The aim of this study was to investigate the
      relationship between NMDA receptor blockers and CRPS. METHOD: Three patients
      suffering from CRPS of one upper extremity where treated with oral NMDA
      antagonist Memantine for eight weeks. Patients expressed their pain levels with a
      visual analog scale ranging from zero to ten at rest and after fist clenching.
      Furthermore, the range of movement of the fingers and the wrist were documented.
      To assess force, a pinchmeter and a dynamometer were used. Cortical
      reorganisation was studied with functional Magnetic Resonance Imaging (fMRI) and
      Magnetoencephalography (MEG). RESULTS: Six months after treatment with Memantine
      no rest pain was present in any of the patients. Furthermore, an increase in
      finger movement was observed after six-month follow-up with no deficits and free
      movement ranges. Additionally, wrist movement was improved and an increase of
      force was measured after six months with the dynamometer and the pinchmeter.
      Moreover the functional impairment, cortical reorganisation was observed in all
      patients before treatment. These changes returned to a normal pattern after eight
      weeks of treatment with Memantine. CONCLUSION: These first results demonstrate
      central nervous system involvement in the development and maintenance of CRPS.
      The results (functional, pain, fMRI, MEG) after treatment with Memantine indicate
      the importance of the NMDA receptor system in neuropathic pain syndromes and
      provide a promising approach for the treatment of CRPS.

PMID- 16883502
TI  - [Is a differentiated treatment depending on the degree of severity justified in
      cubital tunnel syndrome?].
AB  - BACKGROUND: Cubital tunnel syndrome is the second most common chronic nerve
      entrapment of the upper extremity, yet both diagnosis and staging of the severity
      of the progression of the disease rely mostly on the keen observation and
      interpretation of clinical signs and symptoms. To be valid, a staging system must
      correlate well with the known pathophysiological mechanisms of chronic nerve
      compression, have objective parameters available to quantify differing degrees of
      sensory and motor dysfunction, and finally must allow different therapeutic
      consequences. PATIENTS AND METHODS: In this study we have prospectively evaluated
      44 patients who presented with the clinical diagnosis of cubital tunnel syndrome.
      Quantitative Sensory Testing was performed using a computer-assisted testing
      system (Sensory-Management Services L. L. C., Baltimore). Classic two-point
      discrimination, one point pressure threshold, pinch and grip strength were
      measured. Progression of disease was staged according to the gradual loss of
      sensory and motor function. After an average of 15 months postoperatively, ulnar
      nerve function was re-evaluated using the same parameters and outcome measured
      with the modified Bishop rating scale. RESULTS: The results of this study
      indicate that 100 % of patients in the moderate group had a good and excellent
      outcome, whereas only 74 % of the severe group were rated as good and excellent
      with 17 % moderate and 9 % poor outcome.

PMID- 16883503
TI  - [Reduction of the amputation rate in bone and soft tissue sarcoma by
      interdisciplinary cooperation].
AB  - On the basis of three patients with bone and soft tissue sarcoma,we would like to
      illustrate the necessity of a well working inter-disciplinary cooperation of
      radiologists, internal oncologists, radiation therapists, orthopaedic surgeons
      and plastic surgeons. Functional extremity preservation in sarcoma patients can
      be achieved by a good interdisciplinary management without im-pairing the total
      prognosis of the patients. Patients with sarcoma should be treated in centres in
      which all specialised divisions are experienced and well trained in the treatment
      of tumour patients. Only then can a promising approach be achieved.

PMID- 16883504
TI  - [Malignant eccrine poroma].
AB  - INTRODUCTION: Malignant eccrine poroma is a very rare tumour of the sweat glands
      with high malignancy and presenting with a polymorph clinical and histological
      picture. CASE REPORT: We describe the case of a 99-year-old patient with a
      malignant poroma on the buttock. Despite the large size of the tumour, no
      metastasis was found with standard examination techniques. Radical excision and
      defect closure with a Limberg flap was performed. RESULT: The healing course was
      uneventful and without complications. CONCLUSION: The malignant poroma is a
      tumour of high malignancy which can easily be misdiagnosed because of its
      different forms of presentation. Radical surgical therapy is the only known
      effective treatment.

PMID- 16883505
TI  - [Secondary malignant transformation of an enchondroma of the hand].
AB  - The discussion in literature about chondrosarcoma of the hand arising from
      solitary preexistent enchondroma is very controversial. Well-documented, proved
      cases are rare. Treatment of choice a 77-year-old woman with chondrosarcoma
      (Grade 2) of proximal phalanx of the right index finger was ray resection. The 43
      year-old X-ray film showed typical enchondroma in diaphysis of this finger. We
      concluded a long-time period for malignant transformation of a benign enchondroma
      on hand skeleton localisation.

PMID- 16883507
TI  - [Intracranial and intramedullary peripheral nerve sheath tumours. Case reports
      from 20 autopsies].
AB  - INTRODUCTION: Tumors arising from the sheath of peripheral nerves, both
      intracranial and intraspinal, are uncommon and are sometimes of difficult
      clinical diagnosis, especially when they occur in unusual sites. Schwannomas,
      neurofibromas and perineuromas are depicted in this descending order of
      frequency. Most are sporadic and some can be part of hereditary syndromes.
      Histological malignancy of this neoplasm is rare. MATERIALS AND METHODS: The
      clinical and pathological findings of 20 autopsy cases of intracranial and
      intraspinal peripheral nerve tumors are analyzed. The average age at presentation
      was 35 years and the male/female ratio was 1:1. RESULTS: 19 were schwannomas, 13
      of the 8th cranial nerve (two associated with neurofibromatosis type 2), two
      originated in the trigeminal and one in the 12th nerves. Three were intraspinal,
      one of this underwent malignant changes and was part of neurofibromatosis type 1
      (NF-1), another was an intraspinal lumbar mass with schwannomatosis and the third
      was a case of multiple intraspinal neurofibromas as a part of NF-1. 14 cases were
      surgically treated and the causes of death were ischemic lesions due to the large
      size of the tumors. The correct clinical diagnosis was made in 14 patients. In 11
      instances there was corroboration by biopsy. Three were misdiagnosed and three
      were autopsy findings. CONCLUSIONS: In this series more cases were sporadic. No
      sex predominance was encountered. The importance of early detection on
      intracranial and intraspinal peripheral tumors is paramount, since the large size
      of these histologically benign neoplasms makes them biologically malignant.

PMID- 16883506
TI  - [Topiramate in comorbid disorders: epilepsy and migraine].
AB  - INTRODUCTION: With relative frequency epilepsy and migraine are associated in a
      same patient. Some times it is difficult to distinguish an attack of others.
      Reason why it would be of utility to have a treatment effective in both
      pathologies. It is tried to study in patients with this comorbidity, how of
      effective it is a drug indicated in the two pathologies, as it is topiramate.
      PATIENTS AND METHODS: An observational, longitudinal and prospective study is
      made, where 15 patients are recruited with this association, and which they were
      treated with topiramate. They are revaluated at three and six months of
      treatment. RESULTS: Significant differences are obtained (p < 0.05) in all the
      studied variables (severity and duration of the migraine attacks and frequency of
      the migraine and epileptic attacks), with a medium dose of 100 mg/day of
      topiramate, at the end of the study. Not serious adverse effects were observed.
      CONCLUSIONS: Topiramate in monotherapy seems to be a suitable treatment in
      patients who undergo epileptic and migrainous attacks jointly.

PMID- 16883508
TI  - [Neuropathic pain in Fabry's disease: heterogeneous remission in three years of
      enzyme replacement therapy].
AB  - INTRODUCTION: Fabry's disease is associated with acute neuropathic pain (NP).
      When six males with classic Fabry's disease ended three years of enzyme
      replacement therapy (ERT), studies were conducted to analyse the progression of
      the NP. PATIENTS AND METHODS: All of them received 1 mg/kg of agalsidase beta
      every 14 days. NP in hands and feet was evaluated at 0, 6, 12, 24 and 36 months,
      two modalities being considered: a) very intense pain or Fabry crises (FC), which
      forced the patient to rest, take analgesics and apply cold locally; b)
      acroparesthesias (AP), lower intensity itching, tingling and burning sensations
      that did not prevent them from continuing with their activities of daily living.
      The intensity of the FC (IFC) and the AP (IAP) were recorded using the Visual
      Analogue Scale, and the frequency with which both (FrFC and FrAP, respectively)
      appeared was measured in days. The one-tailed Wilcoxon test, binomial
      distribution and bootstrap method were used to carry out the analysis. RESULTS:
      After six months of ERT the IFC, IAP and FrCF remained the same, although the
      FrAP had become worse. As shown by the NP indexes that relate IFC/FrFC and
      IAP/FrAP, progress was therefore favourable. At one year, IFC continued, but FrFC
      and IAP were lower. At two years, the four NP measurements improved in five
      patients, although the FC and AP indexes did not vary in one patient. At three
      years, all the NP variables improved in the six patients. The slope representing
      NP as a function of time in all the bootstrap analyses was found to be p < 0.001.
      CONCLUSIONS: NP responded in a favourable, significant and heterogeneous manner
      and therefore justifies the early indication of ERT.

PMID- 16883509
TI  - [Tumour of the corpus callosum: the association between interhemispheric
      disconnection and an anterograde amnesia syndrome].
AB  - INTRODUCTION: Sperry, or interhemispheric disconnection, syndrome was reported in
      patients who had undergone surgical section of the corpus callosum carried out in
      an attempt to control medication-resistant epilepsy. It has occasionally been
      linked to tumours of the corpus callosum and, although even more rarely, it has
      also been associated to an amnesic syndrome. In this paper we report the
      anatomical and neuropsychological findings in a patient with interhemispheric
      disconnection syndrome associated to a hippocampal-type amnesic syndrome, caused
      by a tumour in the splenius of the corpus callosum that extended into the fornix.
      CASE REPORT: A 52-year-old white male who visited because of loss of memory; on
      admission to hospital the physical examination revealed a certain degree of
      asomatognosia with regard to the left-hand side of the body. An axial tomography
      brain scan showed a dense central lesion in the brain that extended laterally and
      occluded the body of both lateral ventricles. A biopsy study revealed an
      undifferentiated astrocytoma that affected the corpus callosum and the fornix.
      CONCLUSIONS: Sperry, or interhemispheric disconnection, syndrome produced by a
      tumour in the splenius of the corpus callosum is very likely to course with an
      amnesic syndrome due to disconnection caused by destruction of the fornix. This
      association, which characterised our patient's clinical picture, has only
      previously been described in three cases.

PMID- 16883510
TI  - [The medulloblastoma].
AB  - INTRODUCTION AND DEVELOPMENT: Medulloblastoma is a cerebellar small cell tumor,
      whose ancestor cell has not been yet identified in the human normal embriology:
      its exact origin is, in fact, still unknown. Nevertheless, one of the most
      acceptable possibilities facing the origin of the tumor is the remaining rests of
      cerebellar outer granular sheet. It is a predominantly infantile tumor, less
      frequent in young adults, and World Health Organization (WHO) classification has
      assignated grade IV of malignancy. In this publication of the WHO,
      medulloblastomas have been subclassified into: classic, desmoplastic,
      medulloblastomas with extensive nodularity and advanced neuronal differentiation
      and large cell medulloblastomas. Real differences dealing with survival and
      prognosis amidst these subvarieties have been noted in extensive series.
      CONCLUSION: The most frequently genetic alteration is the presence of
      isochromosome 17q in most of 50% of the cases.

PMID- 16883512
TI  - [Acalculia: its classification, aetiology and clinical management].
AB  - AIM: To carry out a review of the literature on the different neurological
      mechanisms involved in processing calculations, the injuries to brain structure
      that can result in acalculia and the clinical management of these patients.
      Development and conclusions. Acalculia is defined as the disorder affecting the
      ability to calculate that is acquired as the result of a brain injury. Despite
      being a frequent symptom and its association to numerous systemic and
      neurological diseases, no clear study protocol exists due to the fact that,
      first, it is usually accompanied by other, more important neurological symptoms
      and, second, it occurs in a very heterogeneous population, where clear
      differences can be seen according to the sociocultural level of the patient.
      Acalculia has been associated both to general alterations of the central nervous
      system and to others affecting local structures. Perhaps the most striking
      example of the former is the case of dementias, where it has even been suggested
      that it could be an early sign of Alzheimer's disease. With respect to the
      latter, the most notable are those affecting the left parietal lobe. In this
      article the following are discussed: 1) the different classifications that have
      been developed for the loss of the ability to calculate; 2) the involvement of
      the different structures of the nervous system in numeric processing, based on
      the associated structural lesions and on studies that have been conducted using
      functional tests and brain imaging; and 3) the different neuropsychological
      instruments that are available to study this capacity.

PMID- 16883511
TI  - [Psychiatric and cognitive complications arising from subthalamic stimulation in
      Parkinson's disease].
AB  - INTRODUCTION AND DEVELOPMENT: Subthalamic stimulation is a therapeutic option
      that can be used to treat advanced cases of Parkinson's disease. However,
      psychiatric or cognitive disorders have been reported in some patients treated
      using this technique. Age and a long disease history are two important risk
      factors for the appearance of these problems. The complications that have been
      reported include cases of depression, apathy, manias and psychosis. Surgery can
      also exacerbate the syndrome of addiction to levodopa that is sometimes observed.
      In contrast, sleep disorders usually improve with this technique. As far as the
      cognitive sphere is concerned, verbal fluency has been seen to deteriorate and
      the executive functions become impaired in patients over 69 years of age. These
      disorders are usually due to a number of different causes and have been
      attributed to the action of stimulating areas close to the subthalamic nucleus,
      to the presence of previously existing cognitive or psychiatric problems, to
      unrealistic expectations about this technique or to the individual's inability to
      adapt to the functional situation after surgery. CONCLUSIONS: Although generally
      speaking these disorders are not usually serious, they must be borne in mind so
      that adequate treatment can be indicated.

PMID- 16883513
TI  - [The impact of migraine and other primary headaches on the health system and in
      social and economic terms].
AB  - INTRODUCTION: Primary headaches are characterised by their high rates of
      prevalence and incidence among the general population. DEVELOPMENT: The main
      types of primary headaches that produce a significant social and economic impact
      as well as an important effect on the health system are migraine and tension-type
      headaches. Migraine is a condition that gives rise to a high percentage of visits
      to different health professionals and leads to a large number of prescriptions
      for medication, which in turn produces an increase in costs. Moreover, general
      practitioners and other specialists -even from the field of neurology- very often
      have scant knowledge about primary headaches, especially as regards topics
      concerning new therapies, the use of the International Headache Society's
      diagnostic criteria, epidemiology and comorbidities. Furthermore, many of these
      professionals seldom attend accredited courses in education in headaches and this
      means that the follow-up of the patients is often inadequate. CONCLUSIONS: The
      appearance of new pharmaceuticals for the abortive and preventive treatment of
      headaches, together with the creation of specialised headache centres, has
      allowed improvements to be made in the treatment of patients with lower overall
      costs for the health system. At the same time, occupational and personal
      productivity and quality of life have also been enhanced. Nevertheless, because
      the number of specialised headache centres is low and their implementation is
      more complex, there is a need for the creation and dissemination of programmes to
      educate general practitioners and other health care specialists in matters
      concerning headaches. Some of these programmes currently being run have obtained
      statistically significant positive results (p < 0.0001).

PMID- 16883514
TI  - [Neonatal Gorlin syndrome associated to hemimegalencephaly confirmed by genetic
      study].

PMID- 16883515
TI  - [Hyperlexia and pseudotetanus in Hashimoto's encephalopathy].

PMID- 16883516
TI  - [Myoclonic seizures induced by tramadol in patients with juvenile myoclonic
      epilepsy].

PMID- 16883518
TI  - [Attending and treating patients who have suffered a transient ischemic attack].

PMID- 16883519
TI  - [The effect of CACNA1H gene G773D mutation on calcium channel function].
AB  - OBJECTIVE: To study the effect of CACNA1H gene mutation G773D on calcium channel
      function. METHODS: By the overlap extension PCR we introduced G773D mutation into
      a human Cav3.2acDNA for constructing the mutant. And then using whole cell clamp
      technique, we studied the alterations of channel behavior in transfected HEK-293
      cells. RESULTS: There were no difference in kinetics of activation and
      inactivation of calcium channel between wild type and mutant. However comparing
      with the wild-type Cav3.2 channel, G773D mutant could increase the calcium
      current density significantly. CONCLUSION: CACNA1H gene G773D mutation is able to
      increase calcium current and neuronal excitability.

PMID- 16883520
TI  - [Clinical and mutational analysis of KCNQ3 gene in a Chinese family with benign
      familial neonatal convulsions].
AB  - OBJECTIVE: To study the clinical and genetic characteristics of a Chinese family
      with benign familial convulsions (BFNC). METHODS: The clinical data of this
      family was analyzed. The blood samples were collected from 13 members of this
      family. By four microsatellite markers which are located in the gene loci of both
      K+ channel KCNQ2 and KCNQ3, the linkage analysis was performed in the family.
      With DNA direct sequencing and restriction endonuclease cutting analysis, the
      mutation analysis of KCNQ3 gene was made for the proband, other 12 family members
      and 76 unrelated normal individuals. RESULTS: There were 7 patients with BFNC
      observed in the three generation of family. The BFNC seizures of all patients
      disappeared during one month and no recurrence of seizures was found. The linkage
      analysis suggested the disease gene linked to KCNQ3 gene locus in the family. The
      mutation 988(C to T) of KCNQ3 gene was found in the proband by DNA-direct
      sequencing. Cosegregation of this mutation with BFNC was confirmed by restriction
      endonuclease cutting analysis. CONCLUSION: Chinese patients with BFNC can be
      caused by KCNQ3 gene mutation.

PMID- 16883521
TI  - [Analysis of ARSA mutations in a Chinese family with metachromatic
      leukodystrophy].
AB  - OBJECTIVE: To identify arylsulftase A gene (ARSA) mutations in a Chinese family
      with MLD. METHODS: There were two MLD patients in the investigated family. The
      proband, an 11-year-old girl, was well until the age of 5 years, when she began
      to experience difficult walking and mental regression. Magnetic resonance imaging
      (MRI) of her brain showed widespread demyelination, nerve conduction velocity
      reduced, and ASA activity measured in white blood cells was zero. So, the child
      was diagnosed having MLD. The proband's young brother also got the same phenotype
      except clinical symptom being milder than hers. Their parents and elder sister
      all had normal phenotypes. Genomic DNA samples were extracted from peripheral
      bloods of the proband and all her family members. All 8 exons and exon-intron
      boundaries of ARSA gene were amplified by polymerase chain reaction (PCR) and
      followed by direct DNA sequencing. RESULTS: Two heterozygous mutations of ARSA,
      which were named as, G251A (R84Q) and G296T (G99V) were identified in the
      proband. The two mutations were located in exon 2. The same genotype was found in
      the proband's young brother, but these mutations were not detected in proband's
      elder sister. The proband's mother had the heterozygous mutations G296T (G99V),
      and her father had the heterozygous mutation G251A (R84Q). CONCLUSION: These two
      MLD patients are with both compound heterozygous mutations, which mean one allele
      with the G296T (G99V) mutation was from their mother, and the other allele with
      the G251A (R84Q) mutation got from their father. The parents are both carrier
      with normal phenotype.

PMID- 16883522
TI  - [Study on genetic polymorphisms of CYP2F1 gene in Guangdong population of China].
AB  - OBJECTIVE: To investigate the genetic polymorphism of CYP2F1 gene, a member of
      CYP450 gene family in the healthy population and the patients with nasopharyngeal
      carcinoma (NPC) of Guangdong province, and furthermore analyze the relationship
      between CYP2F1 genetic polymorphism and the risk of developing NPC. METHODS: By
      direct gene sequencing, all of 10 exons of CYP2F1 gene were detected in 40
      peripheral blood specimens of patients with primary NPC. For the genetic
      polymorphism with high allelic frequency, mismatch PCR-RFLP technique was
      developed to identify the different frequency between 368 NPC cases and 344
      cancer-free controls. RESULTS: There were totally 35 SNPs identified in all of 10
      exons and exon-intron junctions of CYP2F1 gene from 40 NPC patients, which
      included 10 missense mutations and 1 frame shift mutation. The most important
      mutation was C insertion located in 15-16 bp, which caused the frame shift. The
      allelic frequency of C insertion was 25%. However, there was no significant
      difference found between 368 NPC cases and 344 controls in allelic frequency of
      15-16 bp C insertion mutation (P>0.05). CONCLUSION: A lot of genetic polymorphism
      of CYP2F1 gene is found in Guangdong population of China. However, no single
      genetic polymorphism associated with the individual susceptibility to NPC can be
      identified. The cooperated operations with multiple genetic polymorphisms of one
      or more genes may be critical factors contributing to the development and
      progression of NPC.

PMID- 16883523
TI  - [A novel APC gene germline mutation in a familial adenomatous polyposis
      pedigree].
AB  - OBJECTIVE: To detect the adenomatous polyposis coli (APC) gene germline mutation
      in the proband and her family members with familial adenomatous polyposis (FAP).
      METHODS: The diagnosis of a patient with FAP was validated by colonoscopy,
      pathology and the family history. The systematic screening with multiplex
      ligation-dependent probe amplification (MLPA), denaturing high-performance liquid
      chromatography (DHPLC) and DNA sequencing were carried out to detect APC gene
      germline mutations. RESULTS: A novel mutation c.1999 C >T (Q667X) of APC, which
      leads to premature termination of the protein, was identified in this family.
      This mutation manifested an aggressive form of FAP with early onset of colorectal
      adenocarcinoma and colonic adenoma. CONCLUSION: The mutation of APC Q667X is the
      cause of clinical phenotype of this family with FAP, and the prophylactic
      colectomy for the affected family members should be considered.

PMID- 16883524
TI  - [Identification of disease-causing point mutations in DMD patients' dystrophin
      gene without large deletions/duplications].
AB  - OBJECTIVE: To detect the disease-causing point mutations in the dystrophin gene
      of Duchenne muscular dystrophy (DMD) patients. METHODS: The approach of
      denaturing high performance liquid chromatography (DHPLC) coupling with
      sequencing was used to screen the point mutations of 79 exons and the
      untranslated regions of dystrophin gene without large deletions/duplications,
      which was in 6 unrelated DMD probands from 6 DMD families. RESULTS: Five disease
      causing mutations, 697-698insGT, C616T, G1255T, C4279T, and C2302T, were ides
      created the new stop codons in downstream sites of mutations, respectively. In
      addition to the disease-causing point mutations, a point mutation T5586+61A in
      intron 39 was also found at patient 3, and a missense mutation A694T in exon 8
      was detected at patient 5. Four point mutations, C2168+13T, 5740-13dupG, G5234A
      and C5280T, were also detected at patient 6 whose causative point mutation was
      unavailable. Seven point mutations have not been reported previously. Bi
      directional PCR amplification of specific alleles (Bi-PASA) method was
      established to distinguish the haplotypes of heterozygote or homozygote in a
      single PCR reaction. CONCLUSION: Via automated DHPLC screening or detecting the
      subexonic mutations in dystrophin gene is feasible to clinical laboratories, and
      also is a superior method in terms of sensitivity and efficiency.

PMID- 16883525
TI  - [Relationship between the polymorphism of start codon and CDX2 site in vitamin D
      receptor gene and the effect of calcium supplementation on bone mineral density
      of postmenopausal women].
AB  - OBJECTIVE: To investigate the association of polymorphisms of start codon (Fok I
      site) and CDX2 binding site in vitamin D receptor gene (VDR) concerned with the
      effect of calcium supplementation on bone mineral density (BMD) and bone turnover
      markers of postmenopausal women. METHODS: Two hundreds unrelated postmenopausal
      women of Han ethnicity in Shanghai were randomly divided into 2 groups of 100
      women: high calcium group (1000 mg element calcium and 400 units of vitamin D
      were given daily for 12 months) and low calcium group (300 mg element calcium and
      300 units of vitamin D were given daily for 12 months). BMD and bone turnover
      markers were measured at baseline and 12 months after calcium supplementation.
      VDR gene Fok I and CDX2 polymorphisms were analyzed using polymerase chain
      reaction-restriction fragment length polymorphism (PCR-RFLP) and allele-specific
      multiplex PCR, respectively. RESULTS: One hundred and seventy-one women completed
      12-month study period. The frequency of VDR Fok I genotypes was 48.0 % for Ff,
      31.0 % for FF, and 21.0 % for ff, and the frequency of CDX2 genotypes was 56.7 %
      for AG, 25.7% for GG, and 17.6% for AA. The frequencies distribution of Fok I and
      CDX2 alleles in the entire population or in two subgroups all followed the Hardy
      Weinberg equilibrium. No significant difference of baseline BMD and bone turnover
      markers in Fok I genotypes or CDX2 genotypes was observed in the entire
      population or in two subgroups. Moreover, regardless of calcium supplementation
      given for 12 months, no significant association was found between Fok I or CDX2
      polymorphisms and the endpoint values or percentage changes of any BMD and bone
      turnover markers in either high calcium group or low calcium group. CONCLUSION:
      There is no significant relationship between VDR gene Fok I or CDX2 polymorphisms
      and the effect of high or low doses calcium supplementation on BMD and bone
      turnover markers in Shanghai postmenopausal women of Han ethnicity.

PMID- 16883526
TI  - [Study on association between vitamin D receptor gene polymorphisms and the
      outcomes of HBV infection].
AB  - OBJECTIVE: To explore whether the vitamin D receptor gene (VDR) polymorphisms are
      associated with the outcomes of hepatitis B virus (HBV) infection in Chinese Han
      population. METHODS: Polymerase chain reaction-restriction fragment length
      polymorphism (PCR-RFLP) was used to detect the polymorphisms of Fok I locus in
      exon 2 and Taq I locus in exon 9 of VDR gene. One hundred and eighty-four chronic
      hepatitis B patients and 205 asymptomatic HBV carriers were recruited to make the
      comparison of frequencies of genotype and haplotype of the VDR gene between the
      patients and the carriers. RESULTS: The univariate analysis showed a significant
      difference in Fok I polymorphism between chronic hepatitis B patients group and
      asymptomatic HBV carriers group. The FF genotype frequency in chronic hepatitis B
      patients group was 44.6%,higher than 31.7% in asymptomatic HBV carriers group
      (P<0.05). After adjusting the confounders by multiple logistic regression
      analysis, the result still showed a significant difference in Fok I site
      polymorphism between chronic hepatitis B patients group and asymptomatic HBV
      carriers group (OR=1.95, P<0.05). The FT haplotype frequency in chronic hepatitis
      B patients group was higher than that in asymptomatic HBV carriers group
      (OR=1.45, P<0.05). The fT haplotype frequency in chronic hepatitis B patients
      group was lower than that in asymptomatic HBV carriers group (OR=0.72, P<0.05).
      CONCLUSION: VDR gene polymorphism may be an influence factor of genetic
      susceptibility to HBV infection.

PMID- 16883527
TI  - [Scanning the HNF4A gene mutation from Chinese pedigrees with early- and/or
      multiple-onset diabetes].
AB  - OBJECTIVE: To screen the mutation of hepatocyte nuclear factor 4 alpha gene
      (HNF4A) in Chinese pedigrees with early and/or multiplex-onset diabetes in
      Shanghai and nearby area. METHODS: By PCR-single strand conformation polymorphism
      (PCR-SSCP) and direct sequencing, the mutation screen of HNF4A gene was performed
      in 93 normal controls and 154 unrelated probands from early- and/or multiplex
      onset diabetes. The PCR-RFLP was used to analyze the frequencies of the
      discovered mutations and variants. RESULTS: Two synonymous mutations (N153N,
      A158A) were found in two families, of which the N153N was co-segregated with
      early-onset diabetes. These two synonymous mutations were not detected in the 93
      normal controls. Three variants, IVS1+308(A to G)(rs2071197), IVS1+357(A to
      T)(rs2071198), IVS1-5(C to T)(rs745975), were also identified in this study. The
      genotype and allele frequencies of the three variants had no difference between
      the probands and normal controls. CONCLUSION: HNF4A gene mutation is rare in
      Chinese pedigrees with early and/or multiplex-onset diabetes.

PMID- 16883528
TI  - [Associated study on interleukin 10 gene promoter polymorphisms related to
      hepatitis B virus infection in Chinese Han population].
AB  - OBJECTIVE: To investigate the association that the polymorphisms of interleukin
      10 gene (IL10) promoter region are related to the susceptibility and clinical
      phenotypes of hepatitis B virus (HBV) in Chinese Han population. METHODS: With
      polymerase chain reaction with restriction fragment length polymorphism (PCR
      RFLP) method, the single nucleotide polymorphisms (SNP) of the promoter region of
      IL10 gene at position -1082G/A, -819T/C, -592A/C were detected in 231 patients
      with chronic hepatitis B, 165 individuals spontaneously recovered from HBV
      infection and 135 normal controls. RESULTS: No significant difference was found
      in frequencies of genotypes and alleles of IL10 gene promoter region at position 
      1082G/A, -819T/C, -592A/C among normal controls, individuals spontaneously
      recovering from HBV infection and patients with chronic hepatitis B (P>0.05),
      also between patients with HBV infection with HBV-DNA<1x10(3)copies/mL and those
      with HBV-DNA> or =1 x 10(3)copies/mL (P>0.05). However, frequencies of TT
      genotype at position -819T/C and AA genotype at position -592A/C in chronic
      hepatitis B were significantly higher than that in asymptomatic HBV carriers
      (P<0.05). CONCLUSION: It is possible that genetic polymorphisms of IL10 promoter
      region are not associated with both susceptibility of HBV infection and HBV-DNA
      replication after infected HBV in Chinese Han population. However, the
      polymorphisms of the promoter region IL10 at position -819T/C and -592A/C are
      related to inflammatory reaction to liver of the patients with HBV infection.

PMID- 16883530
TI  - [Lecithin-cholesterol acyltransferase gene 608C/T polymorphism associated with
      atherosclerotic cerebral infarction].
AB  - OBJECTIVE: To explore the distribution of lecithin-cholesterol acyltransferase
      gene (LCAT) 608C/T polymorphism in Chinese Han population and the relationship of
      the polymorphism association with the occurrence of atherosclerotic cerebral
      infarction. METHODS: The lecithin:cholesterol acyltransferase gene 608C/T
      polymorphism is identified by polymerase chain reaction (PCR), single-strand
      conformation polymorphism (SSCP)and restriction fragment length polymorphism
      (RFLP) in 150 patients with ACI and 122 healthy controls matching age and sex.
      RESULTS: The distribution of LCAT 608C/T gene polymorphism was in accordance with
      Hardy-Weinberg equilibrium. The CT genotype frequency (14.0%) and T allele
      frequency (7.0%) in ACI group were significantly higher than those in control
      group (P<0.05). The concentration of high density lipoprotein cholesterol (HDL-C)
      in 608CC subgroups were significantly higher than those in 608CT subgroups both
      in ACI group and in control group (P<0.05). CONCLUSION: The LCAT 608C/T
      polymorphism is possibly a predisposing factor in ACI happening of Chinese Han
      population. T allele frequency is possibly concerned with the metabolism of HDL
      C.

PMID- 16883529
TI  - [Mitochondrial 12S rRNA gene A827G in two pedigrees with nonsyndromic deafness].
AB  - OBJECTIVE: To investigate the relationship of associating mitochondrial DNA 12S
      rRNA gene mutations with non-syndromic and aminoglycoside-induced hearing loss
      happening to Chinese families. METHODS: The diagnosis was validated by hearing
      tests. Blood samples were collected from 20 family members (13 subjects from
      pedigree A and 7 from pedigree B) and 32 sporadic deafness cases. DNA was
      extracted from the leukocytes in blood samples. The gene fragments of
      mitochondrial DNA 12S rRNA, tRNA(Ser(UCN)) and GJB(2) were amplified by
      polymerase chain reaction (PCR). PCR products were analyzed by sequencing.
      RESULTS: The target gene fragments of all individuals were successfully amplified
      by PCR. The mitochondrial DNA 12S rRNA 827 A to G transition was detected from
      all maternal members including 12 patients with hearing loss, which was the
      homoplasmic mutation. Non-maternal members in two pedigrees did not carry this
      mutation. However, the tRNA(Ser(UCN)) A7445G, 12SrRNA A1555G and GJB2 gene
      mutations were not found from both the family members of two pedigrees and
      sporadic patients. One sporadic individual (1/32) who was diagnosed as
      aminoglycoside-induced hearing impairment carried A827G mutation too. CONCLUSION:
      It is confirmed that the mitochondrial DNA 12S rRNA gene is a hot spot for
      mutations associated with non-syndromic inherited hearing loss. The 12S rRNA
      nt827 A to G mutation may play a pivotal role in the pathogenesis of hearing
      impairment in two Chinese pedigrees.

PMID- 16883531
TI  - [Study on TR beta gene mutation in a thyroid hormone resistance syndrome family].
AB  - OBJECTIVE: To detect the gene mutation of thyroid hormone receptor beta (TR beta)
      in a family with thyroid hormone resistance syndrome. METHODS: The genomic DNA
      was extracted from peripheral blood leukocytes of the patient, 14 family members
      and 7 healthy subjects. The exons 7-10 of TR beta gene were amplified by PCR. The
      products of PCR were purified and sequenced directly to detect the gene mutation.
      RESULTS: Five members of this family were confirmed to have the C to G transition
      mutation at nucleotide 1642 site within exon 10 of TR beta gene, which was a
      missense mutation causing the substitution of Proline to Alanine (P453A); and
      also to have the C to T transition mutation at nucleotide 1020 within exon 7 of
      TR beta gene, which was a synonymous mutation that didn't cause the change of
      amino acid at this position (F245F). The two mutations were heterozygote. No
      mutation in the exons 7-10 of TR beta gene were identified in other family
      members. CONCLUSION: A family with thyroid hormone resistance syndrome caused by
      TR beta gene mutation is first founded in Chinese people.

PMID- 16883532
TI  - [Association of haplotype formed on HLA-DRB1 and HLA-DQA1 alleles with outcomes
      of hepatitis B virus infection].
AB  - OBJECTIVE: To assess the association of haplotype of HLA-DRB1 and HLA-DQA1
      alleles with outcomes of hepatitis B virus infection in Han population of north
      China. METHODS: Two hundred and seven chronic hepatitis B (HB) patients, two
      hundred and twelve chronic asymptomatic hepatitis B virus (HBV) carriers (HBV
      carrier) and one hundred and forty-eight self-limited HBV infection were
      investigated for HLA-DRB1 and HLA-DQA1 alleles by sequence specific-polymerase
      chain reaction (PCR-SSP). RESULTS: The frequency of DRB1*04-DQA1*0301 haplotype
      was 10.03% in self-limited HBV infection subjects, significantly higher than that
      in chronic HB patients (3.66%) (P=0.0005)uthe frequency of DRB1*15/*16-DQA1*0102
      haplotype was 6.80% in self-limited HBV infection subjects, significantly higher
      than 1.94% in chronic HB patients (P=0.0012) and 1.65% in asymptomatic HBV
      carriers (P=0.0004)uwhile the frequency of DRB1*04-DQA1*0302 haplotype was 3.10%
      in chronic HB patients, higher than that in self-limited HBV infection subjects
      (0.39%) (P=0.0077). CONCLUSION: Individuals with different haplotypes composed of
      HLA-DRB1 and HLA-DQA1 might have different outcomes of HBV infection.

PMID- 16883533
TI  - [Sperm sex chromosome analysis and preimplantation genetic diagnosis of patients
      with sex chromosome anomalies].
AB  - OBJECTIVE: To investigate the constitution of abnormal spermatozoa from patients
      with sex chromosome anomalies. METHODS: Triple color fluorescence in situ
      hybridization (FISH) was used to determine the sex chromosome constitution of
      spermatozoa from three patients with sex chromosome anomalies (case
      1:46,XY/47,XXY, case 2:45,XO/46,X,Yqh-, case 3:47,XXY). The preimplantation
      genetic diagnosis (PGD) was performed to case 2. RESULTS: An increased ratio
      (2.05 vs 1) of X-bearing to Y-bearing spermatozoa was only observed in case 2,
      who also had an increased incidence of total abnormal spermatozoa (29.71%). An
      increased incidence of total abnormal spermatozoa (4.91%) was also observed in
      case 3. Among the constitution of abnormal spermatozoa, case 2 had the increased
      proportions of XY18 disomy, O18 monosomy and XO monosomy, while case 3 had an
      increase proportion of XY18 disomy (1.87%). PGD was performed to case 2 and one
      embryo with XX1818 was selected for implanting. CONCLUSION: Using FISH to detect
      the sperm sex chromosomes in patients with sex chromosome anomalies can provide
      the useful information to evaluate the risk of sex chromosome anomalies in
      preimplantation embryos.

PMID- 16883534
TI  - [An associated analysis of estrogen receptor 2 gene polymorphism linked with
      intrahepatic cholestasis of pregnancy].
AB  - OBJECTIVE: To investigate the relation ship of estrogen receptor 2 gene (ESR2)
      polymorphism associated with intrahepatic cholestasis of pregnancy (ICP) in
      Chengdu of China. METHODS: By polymerase chain reaction-restriction fragment
      length polymorphism (PCR-RFLP) method, the Rsa I polymorphism in exon 5 and the
      Alu I polymorphism in exon 8 of ESR2 were detected in 100 pregnant women with ICP
      (ICP group) and 100 normal pregnant women (control group) in Chengdu. RESULTS:
      (1) The frequency of the allele A of Alu I polymorphism in exon 8 was
      significantly higher in ICP group than in control group (P=0.031, OR=1.975), so
      did the frequency of the Aa+AA genotypes (P=0.028, OR=2.144). (2) The genotype
      distributions (rr, Rr and RR) and allele frequencies (r and R) of Rsa I
      polymorphism in exon 5 were not significantly different between the two groups
      (P>0.05). CONCLUSION: The Alu I polymorphism in exon 8 of ESR2 may be associated
      with the susceptibility of ICP in Chengdu. The Aa+AA genotype significantly
      elevated the risk suffering from the ICP. The Rsa I polymorphism in exon 5 of
      ESR2 is not associated with the risk getting the ICP in Chengdu.

PMID- 16883535
TI  - [HLA-DQB1 allele polymorphism and clinical characteristics of 15 familial
      myasthenia gravis cases in north China].
AB  - OBJECTIVE: To investigate the relationship between the HLA-DQB1 allele
      polymorphisms and the clinical features of 15 familial myasthenia gravis (MG)
      cases in north China. METHODS: By polymerase chain reaction-sequence specific
      primers (PCR-SSP), the HLA-DQB1 gene polymorphisms were determined in 64 MG
      patients (15 familial and 49 sporadic) and 52 healthy individuals as control
      group. The clinical characteristics of 15 familial MG patients and 49 sporadic
      were analyzed. The measurement data was analyzed by t test and enumeration data
      by chi-square test. RESULTS: The frequency of DQB1*0501 was significantly
      increased in familial MG, especially in the ocular type, compared with sporadic
      MG (P<0.05, OR=3.08) and healthy controls (P<0.01, OR=4.439). Comparing with
      healthy controls, the frequency of DQB1*0301/4 was increased (P<0.05, OR=2.56),
      while the frequency of DQB1*0601 was significantly decreased (P<0.05, OR=0.33) in
      sporadic MG. The familial patients had an early age of disease onset, but less
      severity and good prognosis. CONCLUSION: The familial MG has distinctive clinical
      features. DQB1*0501 allele is positively related to the genetic susceptibility to
      familial MG patients in north China, especially to the ocular type. DQB1*0301/4
      allele is positively related to the pathogenesis of sporadic MG. DQB1*0601 may be
      a protecting allele for sporadic MG. The phenotype of MG may be the result of
      interaction of hereditary defects and environmental factors. The familial MG may
      be different from sporadic patients in genetic immune mechanism.

PMID- 16883536
TI  - [A study on HLA-DQB1 allele associated with genetic susceptibility to duodenal
      ulcer in Guangdong Hans].
AB  - OBJECTIVE: To study the genetic susceptibility of HLA-DQB1 alleles to duodenal
      ulcer in Chinese Hans from Guangdong area around. METHODS: Hundred and five
      patients with duodenal ulcer and hundred and five healthy controls were examined
      for HLA-DQB1 genotypes. HLA-DQB1 allele typing was carried out by polymerase
      chain reaction with sequence specific primers (PCR-SSP). RESULTS: The allele
      frequency of HLA-DQB1*0602 in patients with duodenal ulcer (64.8%) was
      significantly higher than that in healthy controls (14.3%). CONCLUSION: These
      findings suggest that HLA-DQB1*0602 is a susceptible gene to duodenal ulcer in
      Guangdong Hans of China. And at HLA-DQB1 site, there are immunogenetic
      differences between duodenal ulcer patients and healthy controls.

PMID- 16883538
TI  - [Disequilibrium linkage between the polymorphism in exons 2, 3 and 4 of the MICA
      gene and HLA-B antigen of patient with ankylosing spondylitis].
AB  - OBJECTIVE: To investigate the association between the exons 2 to 4 of the MICA
      gene and ankylosing spondylitis (AS). METHODS: By PCR-SSOP, DNA samples from 56
      AS patients and 112 random healthy individuals, as normal control were genotyped
      to analyse the polymorphism in exons 2, 3, 4 of the MICA alleles. RESULTS:
      MICA*008 was dominant in MICA allele,accounted for 32.14% and 30.36% in AS
      patients and normal controls respectively. The frequency of MICA*007 was
      significantly increased in AS patients, when compared with normal controls (chi
      square=10.18, P<0.05, RR=2.50). No difference was found in the other MICA
      alleles. The haplotype analysis revealed that there were the strong linkage
      disequilibrium between MICA and HLA-B of AS patients, and normal controls. There
      was a difference in MICA*007-B27 between two groups (chi-square=18.46, P<0.05,
      RR=7.47). Both HLA-B27 and MICA*007 were strongly associated with AS. Stratified
      analysis showed that HLA-B27 was significantly relative to AS,while it was not
      found between MICA*007 and AS. CONCLUSION: The increased frequency of MICA
      alleles may be due to its strong linkage disequilibrium with HLA-B27.

PMID- 16883537
TI  - [CHEK2 c.1100delC may not contribute to genetic background of hereditary breast
      cancer from Shanghai of China].
AB  - OBJECTIVE: To investigate the prevalence of CHEK2 c.1100delC mutation among non
      BRCA1/BRCA2 familial/early-onset breast cancer patients in Shanghai. METHODS: One
      hundred and fourteen non-BRCA1/BRCA2 hereditary breast cancer patients were
      analyzed, among whom 76 cases had at least one first-degree relative affected
      with breast cancer and 38 cases were diagnosed as breast cancer below the age of
      40 years without family history. The mutation genotyping of CHEK2 c.1100delC were
      carried out through long-range PCR amplifying of exons 10-14, and followed by
      amplification of exon 10 and then DNA direct sequencing. RESULTS: No c.1100delC
      frame-shift mutation was identified in our studied population. One novel missense
      mutation 1111C>T (p.His371Tyr), located in kinase catalytic domain, was found in
      3 familial breast cancer cases but no one in control group. CONCLUSION: CHEK2
      c.1100delC is rare variant for Chinese population and may not contribute to
      predisposition for hereditary breast cancer in Shanghai. Novel variant -1111C>T
      could be in association with genetic susceptibility to breast cancer. A further
      study is needed to confirm the results.

PMID- 16883539
TI  - [Relationship between PAI-1 gene 4G/5G polymorphism and clinical profile of IgA
      nephropathy].
AB  - OBJECTIVE: It is clear that PAI-1 is a very important factor inhibiting
      extracellular matrix (ECM) degradation in the pathology process of IgA
      nephropathy (IgAN), so we design to investigate the relationship between PAI-1
      promoter 4G/5G polymorphism and IgAN pathogenesis and progression. METHODS:
      Clinical baseline data such as blood pressure, urinary protein excretion, serum
      profile, and extent of renal tissue damage at the time of renal biopsy were
      collected. The genotypes of PAI-1 were profiled by PCR-RFLP. RESULTS: (1) The
      distributions of genotype 4G 4G, 4G5G, 5G5G in PAI-1 gene promoter showed no
      significant difference between the IgAN group (0.33, 0.19, 0.48) and control
      group (0.3, 0.23, 0.47; chi-square =1.63, P>0.05); (2) There is an increasing
      frequency of 4G4G homozygote in the IgAN group who had severe pathology change
      proved by biopsy (0.39 vs 0.28; chi-square =7.86, P<0.05); in the patients
      group,the ones who carried 4G4G genotype got lower Ccr than 4G5G genotype cases
      did (P<0.05). CONCLUSION: The data here suggest that the 4G/5G polymorphism of
      PAI-1 is not a risk factor in IgAN etiology, but may facilitate the process of
      IgAN to end stage renal disease.

PMID- 16883540
TI  - [Correlation between hepatic immunological markers and virus genotype in patients
      with chronic hepatitis C].
AB  - OBJECTIVE: To investigate the hepatic expression of immunological markers
      relevant to a cytotoxic response in relation to viral genotype. METHODS: The
      frozen liver biopsies were obtained from 28 HF genotyped patients and made the
      sections stained. The morphometry was used to analyze the major
      histocompatibility complex class I (MHC-I), CD8, beta(2)-microglobulin (beta(2) 
      mG), HFE and CD68 in the stained sections. Biopsy data of response to therapy
      with interferon were available in 18 cases. RESULTS: CD8+ was usually clustered
      together and localized in portal tracts and sinusoids, and seen to interact with
      MHC I positive lining cells. MHC-I and beta(2) -mG were expressed mainly in
      endothelial and Kupffer cells. HFE was expressed in most round and dendritic
      CD68+ cells. Patients with virus genotype 3a had higher hepatic MHC-I and HFE
      expression, and a better sustained response to interferon (IFN) therapy than
      patients without. CONCLUSION: The MHC-I expression in the liver of patient with
      chronic hepatitis C virus infection seems to relate to viral-genotype. The
      hepatic MHC-I and HFE expression are higher in patients with virus genotype 3a
      than that in patients with non-3a genotype.

PMID- 16883541
TI  - [The genetic relation of four ethnic populations in China's Guizhou is revealed
      by sequence variations of mtDNA D-loop].
AB  - OBJECTIVE: Through maternal inheritance, to explore the genetic structures and
      relationships of Dong, Gelao, Tujia and Yi ethnic population in Guizhou of China.
      METHODS: The mtDNA D-loop hypervariable segment I (HVS I ) in 108 samples of four
      ethnic populations were sequenced. Then, the nucleotide diversity was estimated
      and a phylogenetic tree was constructed by Neighbor-Joining method. RESULTS: In
      the detected 497 bp fragments, 86 polymorphic sites were found, and 82 different
      haplotypes were identified. The phylogenetic tree of four ethnic populations
      showed: Yi, Tujia and Gelao clustered more closely than Dong did. CONCLUSION: Yi
      and Tujia population are very closely related, the reason may be that they either
      originate from a common ancestry or frequently undergo the gene exchanges and
      admixtures. The genetic relationship between Tujia and Gelao population is
      nearer, perhaps because they have settled in the adjacent regions. Dong and Yi
      population show the farthest genetic relationship, this is probably due to their
      different historical origins and geographic segregation.

PMID- 16883542
TI  - [Distribution of HLA-B allele polymorphism of 8962 Han population in Liaoning of
      China].
AB  - OBJECTIVE: To investigate the distribution of genetic polymorphism of HLA-B locus
      in Liaoning Han population. METHODS: The technique of polymerase chain reaction
      sequence specific primers (PCR-SSP) was adopted in genotyping a sample of 8962
      unrelated healthy individuals collected from a Chinese Han population in Liaoning
      area. The allele frequency of HLA-B was calculated and was compared with the
      results from other population. RESULTS: Thirty-four HLA-B alleles were detected.
      The more common HLA-B allele included B*15(14.42%), B*40(14.33%) and
      B*13(11.99%). The B*82 and B*83 were absent. Forty-nine HLA-B antigens were
      detected. CONCLUSION: The HLA-B allele polymorphism distribution of Liaoning Han
      population exhibits its own characteristic and the difference from old south and
      north Han population in China.

PMID- 16883544
TI  - [Analysis of DC-SIGN and DC-SIGNR genetic polymorphism in Chinese Han
      population].
AB  - OBJECTIVE: To understand the genetic polymorphism of DC-SIGN's and DC-SIGNR's
      neck regions in normal Chinese Han population, and to obtain the genetic data of
      the two loci in Chinese Han population. METHODS: The genotypes and alleles of
      repeat sequences of DC-SIGN and DC-SIGNR neck region were typed by PCR, agarose
      gel electrophoresis and sequencing. Polymorphism information content (PIC) of DC
      SIGNR was calculated. RESULTS: DC-SIGN genetic polymorphism was rare. Allele 7
      was most and its frequency was 0.9808. 4-, 5-, 6- and 8- alleles were also found,
      although their frequencies were very low. Caucasians had only 6- and 8- allele
      mutants; DC-SIGNR genetic polymorphism was high, its PIC was 0.5312, 4-,5-,6-,7
      ,8-,9- alleles and 16 genotypes were found in normal Chinese Han population. The
      differences of 6/5,7/4,7/5,7/6,7/7,9/5,9/7,9/9 genotypes distribution and 5-,6-,7
      ,9- alleles frequency between normal Chinese Han population and Caucasian
      population were all extremely distinct (P<0.01). The inserted mutation seemed
      more in Chinese Hans than Caucasian population. CONCLUSION: DC-SIGN and DC-SIGNR
      genotypes and alleles distribution in Chinese Han population are significantly
      different from Caucasian population and with Chinese own population genetic
      characteristics, compared with Caucasians.

PMID- 16883543
TI  - [The genetic polymorphism of HLA-DQA1 and HLA-DQB1 genes of Chinese Han
      population in Jiangsu area is studied by PCR-sequence-based typing].
AB  - OBJECTIVE: To investigate the polymorphism of HLA-DQA1 and DQB1 genes of Han
      population in Jiangsu of China. METHODS: The alleles and haplotypes frequencies
      of HLA-DQA1 and DQB1 genes in 100 unrelated healthy individuals were analyzed by
      using polymerase chain reaction-sequence-based typing (PCR-SBT). RESULTS: Among
      the 7 DQA1 alleles detected, the most common allele was DQA1*0301/02/03 with a
      frequency of 29.5%, which was followed by DQA1*0501, DQA1*0102 and DQA1*0201 with
      frequencies of 18.5%, 17.0% and 12.5%, respectively. Of the 13 DQB1 alleles
      detected, DQB1*0201/02 allele (21.5%) was the most frequent allele, followed by
      DQB1*0301/09 (14.5%), DQB1*0303 (13.5%) and DQB1*0603 (11.5%). The most common
      DQA1 vs DQB1 haplotype was DQA1*0301/02/03 vs DQB1*0303 with a frequency of
      12.5%, which was followed by the DQA1*0201-DQB1*0201/02 (10.5%),DQA1*0501
      DQB1*0201/02 (9.5%) and DQA1*0501-DQB1*0301/09 (7.0%). CONCLUSION: The
      distribution of HLA-DQ alleles and haplotypes in Jiangsu Han population shares
      some genetic characteristics with other population in northern of China, but has
      its own characteristics. The data will provide useful information for
      anthropology, organ transplantation and disease association studies.

PMID- 16883545
TI  - [The genetic polymorphisms of nine Y-STR loci with short fragment size alleles in
      southern Chinese Han population and its application in forensic science].
AB  - OBJECTIVE: To study the genetic polymorphisms of 9 Y-chromosome specific STR loci
      that the allele size is less than 180 bp in length in the southern Chinese Han
      population, and to utilize the studied result to forensic science. METHODS: Nine
      Y-STR loci were amplified by single multiplex PCR, and the PCR products were
      sequenced by using ABI Prism 3100 DNA Sequencer. The allele and haplotype
      frequencies at 9 Y-STR loci were determined in a total of 213 unrelated males
      from southern Chinese Han population. Eighty-four father/son pairs with
      demonstrated paternity and thirty-six non-paternity father/son pairs were
      detected by using our Y-STR multiplex system. RESULTS: Three Y-STR alleles for
      DYS426, five alleles for DYS393, DYS460, DYS391 and DYS389 I respectively, six
      alleles for DYS456, seven alleles for both H4 and DYS388, and eight alleles for
      DYS458 loci were detected in 213 unrelated male individuals. Except for the
      DYS426 locus with a low GD value of 0.1489, the GD values for other 8 Y-STR loci
      ranged from 0.5064 to 0.9133. A total of 178 haplotypes were found at 9 Y-STR
      loci, of which 154 haplotypes were observed only once, and the haplotype
      diversity was 0.9983. None of Y-STR allele mutation was observed in the 84
      father/son pairs with demonstrated paternity. Among the 36 non-paternity
      father/son pairs, two cases could get the paternity exclusions at 2 Y-STR loci;
      and the paternity of 33 cases could be ruled out by 3 or more Y-STR loci; only
      one case was found no exclusion of paternity regardless of detecting 9 Y-STR
      loci. CONCLUSION: This result indicates that the 9 Y-STR loci with short fragment
      size alleles are highly polymorphic. The fluorescent multiplex amplification
      system that we developed is suitable for personal identification and paternity
      testing.

PMID- 16883546
TI  - Determination of piceid in rat plasma and tissues by high-performance liquid
      chromatographic method with UV detection.
AB  - A rapid, sensitive and selective HPLC method was developed and validated for
      determination of piceid in rat plasma and tissues. The drug was isolated from
      plasma and tissues by a simple protein precipitation procedure. Chromatographic
      separation was performed on a C(18) column with acetonitrile-water (26:74, v/v)
      as mobile phase. The method was successfully applied to the pharmacokinetics and
      tissue distribution research after oral administration of a 50 mg/kg dose of
      piceid to healthy male Wistar rats. The pharmacokinetic parameters showed that
      piceid was quickly absorbed, distributed and eliminated within 4 h after oral
      administration. The tissue distribution results showed that, at 10 min, the
      concentrations of piceid in most tissues reached peak level except in heart and
      testis. The highest level of piceid was found in stomach, then in small
      intestine, spleen, lung, brain, testis, liver, kidney and heart. The amount of
      piceid in testis and heart reached the peak level at 30 min. At 120 min, the
      amount of piceid in all tissues decreased to a low percentage of the initial
      concentration. Piceid was absorbed throughout the gastrointestinal tract with
      considerable absorption taking place in the stomach and small intestine. There
      was no long-term accumulation of piceid in rat tissues.

PMID- 16883547
TI  - Determination and pharmacokinetic study of syringin and chlorogenic acid in rat
      plasma after administration of Aidi lyophilizer.
AB  - A high-performance liquid chromatographic (HPLC) method was developed for the
      first time to simultaneously quantify syringin and chlorogenic acid in rat plasma
      using wavelength-transfer technology. The analysis was performed on a Diamonsil
      C(18) column (200 x 4.6 mm i.d., 5 microm particle size) with isocratic mobile
      phase consisting of acetonitrile-0.05% phosphoric acid (12:88, v/v). The linear
      ranges were 0.20-10 and 0.25-30 microg/mL, respectively. The lower limits of
      quantification were 0.20 and 0.25 microg/mL, respectively. The method was shown
      to be reproducible and reliable with intraday precision below 8.5 and 6.1%,
      interday precision below 7.1 and 5.5%, accuracy within +/-7.1 and +/-8.6%, and
      mean extraction recovery excess of 92.1 and 80.9%, respectively, which were all
      calculated from the blank plasma sample spiked with syringin and chlorogenic acid
      at three concentrations of 0.20, 1.0 and 6.0 microg/mL for syringin and 0.25, 2.0
      and 20 microg/mL for chlorogenic acid. This method was validated for specificity,
      accuracy and precision and was successfully applied to the pharmacokinetic study
      of syringin and chlorogenic acid in rat plasma after intravenous administration
      of Aidi lyophilizer.

PMID- 16883548
TI  - Identification of volatile components in Angelica species using supercritical-CO2
      fluid extraction and solid phase microextraction coupled to gas chromatography
      mass spectrometry.
AB  - As a part of our search for environmentally friendly solvents to extract the
      active components of medicinal plants, two sampling techniques, supercritical
      fluid extraction (SFE) using CO(2) and solid-phase microextraction (SPME) were
      compared for their efficacy in the analysis of volatiles rhizome components
      emitted from the medicinal herbs Angelica gigas NAKAI (Korean danggui), Angelica
      sinensis (Chinese danggui), and Angelica acutiloba (Japanese danggui). A total of
      54 compounds released from all of these varieties of Angelica rhizomes were
      separated and identified by gas chromatography-mass spectrometry (GC-MS). The
      composition of supercritical extracts from these plants was very different from
      the solid-phase microextraction products. More compounds were detected by SPME-GC
      MS (41) than by SFE-GC-MS (17). The results of these analyses suggest that SFE
      may be useful for detecting the main components, decursinol angelate and decursin
      in Korean danggui, and butylidene dihydro-phthalide in both Chinese and Japanese
      danggui, whereas the results for SPME did not. The SFE method required
      specialized instrumentation, required little time to prepare the sample, and had
      a small sample size and no organic solvent. In sum, these results suggest that
      SFE is useful for extracting the volatile main components of danggui cultivars.
      Its simplicity, low cost and speed may allow SPME to increase the recovery of
      volatile components in general without disturbing the main components of the
      plant.

PMID- 16883549
TI  - Determination of coenzyme Q10 in human breast milk by high-performance liquid
      chromatography.
AB  - An isocratic HPLC method was developed for the determination of coenzyme Q(10)
      (CoQ(10)) in human breast milk. After a single-step liquid-liquid extraction, the
      milk extract was injected directly into the HPLC system. The analytical method is
      based on pre-column inline treatment of CoQ(10). Chromatographic separation of
      CoQ(10) and coenzyme Q(9) (CoQ(9)) internal standard was achieved using a
      reversed-phase Microsorb-MV C(18) analytical column. CoQ(10) and CoQ(9) were
      monitored by an electrochemical detector (ECD). An excellent linearity (r =
      0.999) was observed for CoQ(10) in the concentration range 0.06-2.5 micromol L(
      1) in breast milk. The limit of quantitation (LOQ) was 60 nmol L(-1).
      Coefficients of variations (CVs) for intra-day and inter-day assay precisions
      were less than 5%. A total of 194 breast milk samples were analyzed for the
      CoQ(10) concentration; the mean value was 0.32 +/- 0.21 micromol L(-1).

PMID- 16883550
TI  - MDR1 haplotypes significantly minimize intracellular uptake and transcellular P
      gp substrate transport in recombinant LLC-PK1 cells.
AB  - To date, research on the effect of single nucleotide polymorphisms (SNPs) on P
      glycoprotein (P-gp) expression and functionality has rendered inconsistent
      results. This study systematically evaluates the impact of MDR1 haplotypes
      (1236/2677, 1236/3435, 2677/3435, 1236/2677/3435) on P-gp functionality compared
      to individual SNPs (1236, 2677, and 3435) in validated stable recombinant
      epithelial cells. Recombinant LLC-PK1 cells expressing MDR1wt or its variants
      were developed and validated for this purpose. Intracellular accumulation and
      time-dependant efflux of a P-gp substrate, Rhodamine 123 (R123, 5 microM) were
      evaluated in control and recombinant cells. Additionally, the transepithelial
      transport of R123 (1 microM) and Vinca alkaloids (5 microM) was evaluated. Except
      for MDR1(2677T) and MDR1(1236T/2677T/3435T), cells expressing MDR1 variants
      displayed intermediate R123 intracellular accumulation (1.5-2-fold higher) and
      lower effluxed R123 (10-20% vs. 52%) compared to those expressing MDR1wt. Efflux
      ratios across MDR1wt expressing cells were significantly larger for R123 (3.95+/
      1.1), Vinblastine (3.75+/-0.26), and Vincristine (2.8+/-0.29). Recombinant cells
      expressing MDR1 variants displayed 0%-22.7% P-gp activity (approximately 80%-100%
      efflux loss). Results suggest that MDR1 polymorphisms at the 1236, 2677, and/or
      3435 positions significantly minimize P-gp functionality in vitro, the extent of
      which appears to be substrate dependant.

PMID- 16883551
TI  - Preparation of budesonide/gamma-cyclodextrin complexes in supercritical fluids
      with a novel SEDS method.
AB  - The aim was to investigate if solid drug/cyclodextrin complexes could be produced
      in a single-step process with a solution enhanced dispersion by supercritical
      fluids (SEDS) method. Budesonide and gamma-cyclodextrin (CD) solutions (50% or
      99.5% ethanol) were pumped from the same (conventional method) or separate
      (modified method) containers together with supercritical carbon dioxide through a
      coaxial nozzle into a particle formation chamber. The pressure was maintained at
      100, 150 or 200 bar with a temperature of 40, 60 or 80 degrees C. SEDS-processed
      powders were characterised with HPLC, DSC and XRPD for budesonide content,
      complexation and crystallinity. The budesonide dissolution rate was determined in
      1% gamma-CD aqueous solution. Solid, white budesonide/gamma-CD complex particles
      were formed using the conventional and modified SEDS processes. The complexation
      efficiency was dependent on the processing conditions. For example, with the
      conventional method (100 bar, 60 degrees C) the yield of the powder was 65+/-12%
      with 0.14+/-0.02 mg budesonide/mg powder, corresponding to 1:2 drug:CD molar
      ratio. The dissolution rate of this complexed budesonide (93+/-2% after 15 min)
      was markedly higher compared to unprocessed micronised budesonide (41+/-10%) and
      SEDS-processed budesonide without CD (61+/-3%). As a conclusion, SEDS is a novel
      method to produce solid drug/CD complexes in a single-step process.

PMID- 16883552
TI  - Biophysical characterization of polymeric and liposomal gene delivery systems
      using empirical phase diagrams.
AB  - A major problem with the pharmaceutical use of nonviral gene delivery systems
      arises from their limited characterization due to their size and heterogeneity.
      In this study, we provide a more intuitive view of their structure and behavior
      employing an empirically based phase diagram approach. Complexes formed between
      plasmid DNA and four cationic carriers (a monovalent lipid, the same monovalent
      lipid combined with a helper lipid, polylysine, and a branched form of
      polyethyleneimine), at both positive and negative nitrogen/phosphorous ratios,
      are characterized employing dynamic light scattering, circular dichroism, and
      extrinsic dye fluorescence as methods sensitive to various aspects of the
      structure of the complexes. These measurements were performed as a function of pH
      and ionic strength to perturb the electrostatic contacts that are key to complex
      formation. Using a multidimensional eigenvalue approach, the data are presented
      in the form of a colored, five dimensional diagram. The resultant eight empirical
      phase diagrams display three to five variably resolved phases. In contrast, the
      phase diagram of the plasmid alone showed only two to three such phases. Each
      state is assigned to a particular form of the complex in terms of their size,
      extent of collapse and conformation of the associated DNA component. The utility
      of this approach is then briefly discussed.

PMID- 16883554
TI  - New DEFT sequences for the acquisition of one-dimensional carbon NMR spectra of
      small unlabelled molecules.
AB  - The acquisition time and quality of 1D 13C{1H} spectra can be improved
      substantially by using a modified driven equilibrium Fourier transform (DEFT)
      sequence, which is specifically designed to compensate for the effects of B1
      inhomogeneity, pulse miscalibration and frequency offsets. The new sequence,
      called uniform driven equilibrium Fourier transform (UDEFT), returns the carbon
      magnetization with a high accuracy along its equilibrium position after each
      transient is complete. Thus, the sequence allows the use of relaxation delays
      (RD), which are much shorter than the carbon T1 of the molecule, thereby speeding
      up the acquisition process of 1D 13C{1H} spectra. To achieve this level of
      performance, UDEFT employs a refocusing element constituted by a composite
      adiabatic carbon pulse surrounded by two 90 degrees carbon pulses whose phases
      are designed to compensate for 90 degrees pulse miscalibrations in an MLEV manner
      (90 degrees+x-tau(FID)-180+y(Adia)-tau-90 degrees+x-180 degrees+x(Adia)). A
      version of the UDEFT sequence allows recording 1D 13C{1H} spectra devoid of
      heteronuclear NOE by using a matched adiabatic 1H decoupling scheme where an even
      number of 180 degrees adiabatic pulses is applied during the UDEFT module.
      Spectra of a solution of 300 mM camphor that contains some carbon nuclei with
      very long T1 relaxation times (90 s and 78 s) were acquired with 128 scans in 10
      min using a 5 s relaxation delay.

PMID- 16883553
TI  - Study of retinoic acid polymorphism.
AB  - Some authors recently hypothesized the existence of a new retinoic acid (RA)
      phase in addition to the two already known polymorphs. We investigated RA
      polymorphism and our results exclude the presence of new modifications and refine
      the properties of the known forms. By comparison of simulated and acquired X-Ray
      Powder Diffraction (XRPD) it was possible to identify only the known monoclinic
      (I) and the triclinic (II) modifications; the same were also characterized by
      DSC, IR, and Raman spectroscopy. A solubility study associated to DSC allowed
      establishing an enantiotropic relationship between the two forms, with form II
      being less stable (DeltaGII/I=0.71 kJ/mol at 37 degrees C) below the transition
      temperature (136.6 degrees C; DeltaH=3.2 kJ/mol). The intrinsic dissolution rate
      (IDR) (I=61 microg/cm2xmin-1; II=125 microg/cm2xmin-1) confirmed this energetic
      relationship. The kinetics of solid transition I-->II was examined and its
      activation energy estimated (356 kJ/mol). The attempts to produce new phases
      allowed the development of methods to obtain the two polymorphs with high
      chemical and polymorphic purity. A validated DSC method is presented that enables
      detection of the presence of form I at a level of 1% (w/w) when in mixture with
      form II.

PMID- 16883555
TI  - Differential role of Presenilin-1 and -2 on mitochondrial membrane potential and
      oxygen consumption in mouse embryonic fibroblasts.
AB  - Increasing evidence indicates that mitochondrial alterations contribute to the
      neuronal death in Alzheimer's disease (AD). Presenilin 1 (PS1) and Presenilin 2
      (PS2) mutations have been shown to sensitize cells to apoptosis by mechanisms
      suggested to involve impaired mitochondrial function. We have previously detected
      active gamma-secretase complexes in mitochondria. We investigated the impact of
      PS/gamma-secretase on mitochondrial function using mouse embryonal fibroblasts
      derived from wild-type, PS1-/-, PS2-/- and PS double knock-out (PSKO) embryos.
      Measurements of mitochondrial membrane potential (DeltaPsim) showed a higher
      percentage of fully functional mitochondria in PS1-/- and PSwt as compared to PS2
      /- and PSKO cells. This result was evident both in whole cell preparations and in
      isolated mitochondria. Interestingly, pre-treatment of isolated mitochondria with
      the gamma-secretase inhibitor L-685,458 resulted in a decreased population of
      mitochondria with high DeltaPsim in PSwt and PS1-/- cells, indicating that
      PS2/gamma-secretase activity can modify DeltaPsim. PS2-/- cells showed a
      significantly lower basal respiratory rate as compared to other cell lines.
      However, all cell lines demonstrated competent bioenergetic function. These data
      point toward a specific role of PS2/gamma-secretase activity for proper
      mitochondrial function and indicate interplay between PS1 and PS2 in
      mitochondrial functionality.

PMID- 16883556
TI  - Towards an understanding of the molecular mechanism of solvation of drug
      molecules: a thermodynamic approach by crystal lattice energy, sublimation, and
      solubility exemplified by paracetamol, acetanilide, and phenacetin.
AB  - Temperature dependencies of saturated vapor pressure for the monoclinic
      modification of paracetamol (acetaminophen), acetanilide, and phenacetin
      (acetophenetidin) were measured and thermodynamic functions of sublimation
      calculated (paracetamol: DeltaGsub298=60.0 kJ/mol; DeltaHsub298=117.9+/-0.7
      kJ/mol; DeltaSsub298=190+/-2 J/mol.K; acetanilide: DeltaGsub298=40.5 kJ/mol;
      DeltaHsub298=99.8+/-0.8 kJ/mol; DeltaSsub298=197+/-2 J/mol.K; phenacetin:
      DeltaGsub298=52.3 kJ/mol; DeltaHsub298=121.8+/-0.7 kJ/mol; DeltaSsub298=226+/-2
      J/mol.K). Analysis of packing energies based on geometry optimization of
      molecules in the crystal lattices using diffraction data and the program Dmol3
      was carried out. Parameters analyzed were: (a) energetic contribution of van der
      Waals forces and hydrogen bonding to the total packing energy; (b) contributions
      of fragments of the molecules to the packing energy. The fraction of hydrogen
      bond energy in the packing energy increases as: phenacetin (17.5%)<acetanilide
      (20.4%)<paracetamol (34.0%). Enthalpies of evaporation were estimated from
      enthalpies of sublimation and fusion. Activity coefficients of the drugs in n
      octanol were calculated from cryoscopic data and by estimation of dilution
      enthalpy obtained from solubility and calorimetric experiments (for infinite
      dissolution). Solubility temperature dependencies in n-octanol and n-hexane were
      measured. The thermodynamic functions of solubility and solvation processes were
      deduced. Specific and nonspecific solvation terms were distinguished using the
      transfer from the "inert" n-hexane to the other solvents. The transfer of the
      molecules from water to n-octanol is enthalpy driven for paracetamol; for
      acetanilide and phenacetin, entropy driven.

PMID- 16883557
TI  - Permeability assessment of poorly water-soluble compounds under solubilizing
      conditions: the reciprocal permeability approach.
AB  - The objective of this study was to develop a general method to assess the
      intestinal permeability of poorly water-soluble drugs where low-aqueous drug
      solubility requires conduct of experiments under solubilizing experimental
      conditions. The permeability (Papp) of diazepam (DIA) was assessed across excised
      rat jejunum in the absence (Pappcontrol) and presence (Pappuncorr) of polysorbate
      80 (PS-80). The micellar association constant (Ka) of DIA, estimated via
      equilibrium solubility studies, was used to correct Pappuncorr data and obtain an
      estimate of the true permeability coefficient (Pappcorr). An alternate approach
      was also developed (the reciprocal permeability approach) to allow direct
      estimation of Pappcorr without the need for independent estimation of Ka. The
      approach was further examined experimentally using a range of model drugs. DIA
      Pappcorr values obtained using the Ka from equilibrium solubility studies
      deviated from Papp(control) values, especially at PS-80 concentrations above 0.1%
      w/v. In contrast, data obtained using the reciprocal permeability method were
      consistent with Pappcontrol across the PS-80 concentration range. Similar trends
      were observed with propranolol (PRO), antipyrine (ANT), naproxen (NAP), and
      cinnarizine (CIN). The reciprocal permeability approach therefore provides a
      simple and accurate method by which the permeability of poorly water-soluble
      compounds may be estimated under solubilizing conditions.

PMID- 16883558
TI  - Hippocampal place cells: parallel input streams, subregional processing, and
      implications for episodic memory.
AB  - The hippocampus is thought to be involved in episodic memory in humans. Place
      cells of the rat hippocampus offer a potentially important model system to
      understand episodic memory. However, the difficulties in determining whether rats
      have episodic memory are profound. Progress can be made by considering the
      hippocampus as a computational device that presumably performs similar
      transformations on its inputs in both rats and in humans. Understanding the
      input/output transformations of rat place cells can thus inform research on the
      computational basis of human episodic memory. Two examples of different
      transformations in the CA3 and CA1 regions are presented. In one example, CA3
      place fields are shown to maintain a greater degree of population coherence than
      CA1 place fields after a rearrangement of the salient landmarks in an
      environment, in agreement with computational models of CA3 as an autoassociative
      network. In the second example, CA3 place field appears to store information
      about the spatiotemporal sequences of place fields, starting with the first
      exposure to a cue-altered environment, whereas CA1 place fields store this
      information only on a temporary basis. Finally, recordings of hippocampal
      afferents from the lateral and medial entorhinal cortex (EC) suggest that these
      two regions convey fundamentally different representations to the hippocampus,
      with spatial information conveyed by the medial EC and nonspatial information
      conveyed by the lateral EC. The dentate gyrus and CA3 regions may create
      configural object+place (or item+context) representations that provide the
      spatiotemporal context of an episodic memory.

PMID- 16883559
TI  - Increase of doxorubicin sensitivity for folate receptor positive cells when given
      as the prodrug N-(phenylacetyl) doxorubicin in combination with folate-conjugated
      PGA.
AB  - Folate receptor (FR) has been proposed as a promising target for tumor drug
      targeting. The aim of this study was to increase the chemo-sensitivity of FR
      positive cells to doxorubicin by folate-directed enzyme prodrug therapy (FDEPT).
      Folate conjugated penicillin-G amidase was prepared and its ability to hydrolyze
      N-(phenylacetyl) doxorubicin was measured by HPLC. Fluorescence and confocal
      image analysis revealed that Folate-PGA can be specifically delivered into FR
      positive HeLa and SKOV3 tumor cells. In vitro cytotoxity assays, IC50 was reduced
      with N-(phenylacetyl) doxorubicin versus doxorubicin for HeLa (3.1-fold
      reduction; p<0.001) and SKOV3 (3.3-fold reduction; p<0.001) when Folate-PGA was
      specifically bound to the cells. Complete activation was confirmed in HeLa and
      SKOV3 cells pretreated with free folic acid (1 mM), where the combination of N
      (phenylacetyl) doxorubicin with Folate-PGA did not show any significant cell
      toxicity to the IC50 of doxorubicin. Pharmacokinetic clearance and
      biodistribution studies in vivo showed that 125I-Folate-PGA was cleared from
      blood within 24 h and had significantly higher tumor uptake compared to 125I-PGA
      (p<0.05). These results demonstrate that the FDEPT approach may be a potential
      promising strategy to improve chemotherapy-resistant cancers therapeutic ratio
      and warranted future studies.

PMID- 16883560
TI  - Transcellular route of diffusion through stratum corneum: results from finite
      element models.
AB  - Insight into the stratum corneum (SC) permeation pathway for hydrophilic
      compounds is gained by comparing experimental measurements of permeability and
      lag time (tlag) with the predictions of a finite element (FE) model. A database
      of permeability and lag time measurements (n=27) of hydrophilic compounds was
      compiled from the literature. Transcellular and lateral lipid diffusion pathways
      were modeled within a brick-and-mortar geometry representing fully hydrated human
      SC. Modeled tlag's for the lipid pathway are too brief to account for the
      experimental quantities, whereas the transcellular pathway with preferential
      corneocyte partitioning does account for them. Measured tlag's are highly
      correlated (p<0.0001) with the compound's octanol-water partition coefficient,
      supporting the hypothesis of an aqueous-lipid partition mechanism in the
      permeation of hydrophilic compounds. The importance of the lag time for
      identifying the diffusion pathway is demonstrated.

PMID- 16883561
TI  - Synthesis and chemical stability of a disulfide bond in a model cyclic
      pentapeptide: cyclo(1,4)-Cys-Gly-Phe-Cys-Gly-OH.
AB  - Many cyclic peptides are formed using a disulfide bond to increase their
      conformational rigidity; this provides receptor selectivity and increased
      potency. However, degradation of the disulfide bond in formulation can lead to a
      loss of structural stability and biological activity of the peptide. Therefore,
      the objective of this study was to study the stability of peptide 1 (cyclo(1,4)
      Cys-Gly-Phe-Cys-Gly-OH). This cyclic peptide was synthesized using Boc strategy
      via solution-phase peptide synthesis and purified using semi-preparative HPLC.
      The accelerated stability studies of the cyclic peptide were conducted in buffer
      solutions at pH 1.0-11.0 with controlled ionic strengths at 70 degrees C. The pH
      rate profile shows that the peptide has an optimal stability around pH 3.0 with a
      V-shape between pH 1.0 and 5.0. Two small plateaus are observed at pH 5.0-7.0 and
      pH 8.0-10.0, indicating hydrolysis on different ionized forms of the cyclic
      peptide. One product was observed at acidic pH due to peptide bond hydrolysis at
      Gly2-Phe3. The number of degradation products increases as the pH increases from
      neutral to basic, and most of the degradation products at neutral and basic pH
      are derived from the degradation at the disulfide bond.

PMID- 16883562
TI  - A process analytical technology approach based on near infrared spectroscopy:
      tablet hardness, content uniformity, and dissolution test measurements of intact
      tablets.
AB  - Near infrared spectroscopy (NIRS) is a nondestructive analytical technique that
      enables simultaneous measurements of chemical composition (viz. the content in
      active pharmaceutical ingredient, API) and various physical properties (viz.
      tablet hardness and dissolution profile) in pharmaceutical tablets. In this work,
      partial least squares (PLS) calibration models and discriminant partial least
      squares (DPLS) classification models were constructed by using calibration sets
      consisting of laboratory samples alone. The laboratory samples were mixtures of
      the API and excipients that were pressed into tablets. API content, tablet
      hardness, and dissolution measurements of intact tablets were made by using three
      different calibration models that are fast--results can be obtained within a few
      seconds--, simple and robust--they involve minimal analyst intervention--, and
      clean--they use no toxic reagent and produce no toxic waste. Based on the
      results, the proposed NIR method is an effective alternative to current reference
      methods for the intended purpose. The advantages provided by NIR spectroscopy in
      this context confirm its potential for inclusion in process analytical
      technologies in the pharmaceutical industry.

PMID- 16883563
TI  - Modulating beta-lapachone release from polymer millirods through cyclodextrin
      complexation.
AB  - Beta-lapachone (beta-lap) is a novel anticancer agent that kills tumors
      overexpressing the NADPH: quinone oxidoreductase enzyme. However, poor aqueous
      solubility and low bioavailability hinder its therapeutic applications. Herein we
      describe the development of poly(D,L-lactide-co-glycolide) (PLGA) polymer
      millirods for local delivery of beta-lap. The objective was to investigate the
      use of beta-lap inclusion complexes with cyclodextrins (CDs) to control beta-lap
      release kinetics from PLGA millirods. Differential scanning calorimetry was
      performed to measure drug/polymer interactions, complexation efficiency with
      different CDs, and complex/polymer interactions. beta-Lap was found to have a
      solid-state solubility of 13% in PLGA. beta-Lap dissolution in PLGA matrix
      lowered the glass transition temperature of PLGA from 44 to 31 degrees C, and led
      to a slow release of beta-lap (8.8+/-1.2% release after 22 days). For beta-lap
      and CD interactions, increasing complexation efficiency was observed in the order
      of alpha-CD, gamma-CD, and beta-CD. beta-Lap complexation with hydroxypropyl-beta
      cyclodextrin (HPbeta-CD) prevented drug dissolution in PLGA, and led to fast
      release (79.6+/-2.1% after 2 days). Sustained drug release was achieved when beta
      lap was complexed with alpha-CD or gamma-CD. These data demonstrate the ability
      to tailor beta-lap release kinetics via CD complexation, providing exciting
      opportunities for the use of beta-lap-millirods for intratumoral drug delivery.

PMID- 16883564
TI  - In situ studies of regional absorption of lobucavir and ganciclovir from rabbit
      intestine and predictions of dose-limited absorption and associated variability
      in humans.
AB  - The regional absorption of lobucavir (LBV), an experimental antiviral agent, and
      ganciclovir (DHPG) was investigated in rabbit intestine using an in situ single
      pass perfusion technique. Duodenal, jejunal, and colonic segments in anesthetized
      rabbits were perfused with drug solutions in a hypotonic buffer at 0.2 mL/min.
      Effluent perfusate samples for drug analysis were collected every 10 min for 180
      min. To account for water absorption during perfusion, an intestinal absorption
      model was developed to estimate the absorptive clearance (PeA):
      PeA=Qavexln((QinxCin)/(QoutxCout)), where Qave is a logarithmic average of the
      inflow (Qin) and outflow perfusion rate (Qout); Cin and C(out) are drug inflow
      and outflow concentrations. The PeA of LBV in the duodenum and jejunum was 2.1+/
      0.77 and 1.7+/-0.46 microL/min/cm (n=3), respectively, 4.8- and 3.0-fold higher
      than that of DHPG in the same animals. However, LBV PeA decreased significantly
      in the colon (0.47+/-0.11 microL/min/cm) and was similar to that of DHPG which
      exhibited no regional differences in absorption. The interplay between PeA and
      solubility was studied using a compartmental absorption and transit model, and
      simulations were performed to investigate dose-limited absorption and the sources
      of variability in absorption where two compounds differ significantly. The dose
      range where absorption started to decrease was predicted using the model, with
      LBV exhibiting the phenomenon at a lower dose than DHPG (450 vs. 750 mg).
      Furthermore, the intersubject variability in human absorption of both compounds
      was reproduced when the variability in both PeA and the small intestinal transit
      time was considered in the model. The variability in the ascending colonic
      transit time also contributed to the intersubject variability observed for DHPG.
      The results demonstrate value of integrating in situ studies and modeling in
      predicting these absorption characteristics.

PMID- 16883565
TI  - Genetic link between Chaoshan and other Chinese Han populations: Evidence from
      HLA-A and HLA-B allele frequency distribution.
AB  - The genetic polymorphism of HLA-A and HLA-B loci was investigated in 505
      Chaoshanese using PCR-SSP method. Among the HLA-A alleles detected, A*11 (35.64%)
      was most frequent, followed by A*02 (31.78%). Of 34 HLA-B alleles tested, 30 were
      observed, in which B*60 (21.68%), B*46 (14.46%), and B*58 (10.69%) were highly
      predominant. Comparison was made with other nine Chinese Han ethnic groups
      covering the Mainland China, Taiwan, Hong Kong, and Singapore. The high frequent
      alleles found in Chaoshanese were also common in other Chinese groups compared
      though the frequency levels varied from group to group. The phylogenic tree
      analysis based on the HLA-A and -B allele frequencies of all the 10 Chinese
      ethnic groups revealed that Chaoshanese, while clustering in general with the
      southern China-related Han Chinese, had the highest affinity to the Mainland
      Minnanese, but separated distinctively from the northern Han Chinese. The study,
      however, was yet to confirm the hypothesis of the Central Plains Han origin of
      Chaoshanese. Interestingly, the alleles (B*46, B*38, and B*58) and the related
      haplotypes (A*02-B*46 and A*33-B*58) that are positively associated with
      nasopharyngeal carcinoma (NPC), a disease prevailing predominantly among southern
      Chinese, were always at much higher frequencies among southern Chinese than among
      northern Chinese, whereas A*31 and B*13, the two alleles with highly protective
      effects for NPC, and the associated haplotype A*30-B*13 were predominantly high
      in northern Chinese. The different genetic background between northern and
      southern China may explain, at least partially, the prevalence of NPC among
      southern Chinese.

PMID- 16883566
TI  - Cranial trauma in iron age Samnite agriculturists, Alfedena, Italy: implications
      for biocultural and economic stress.
AB  - The Samnites are an Iron Age protohistoric people from the central region of
      Italy. The skeletal remains are from the Alfedena necropolis, 6th through 5th
      centuries B.C. Macchiarelli et al. (Antropologia Contemporanea 4 (1981) 239-243)
      were the first to report on cranial trauma for this population, presenting four
      cases with extreme injuries. We re-examined this well documented skeletal
      population for additional examples of trauma. Previously unexamined remains from
      Alfedena, excavated at the turn of the 20th century, are also included in our
      analysis (Mariani. 1901. "Aufidena", ricerche archeologiche e storiche del Sannio
      settentrionale. Roma: Acc Naz Dei Lincei). Of the 209 adult crania examined,
      12.9% of them exhibited trauma. Analysis of location and frequency of cranial
      trauma revealed that cranial injuries to the head appear to originate from all
      directions. The high rate of cranial trauma underscores the violent circumstances
      experienced during the Iron Age protohistoric period of central Italy. Males are
      much more likely to exhibit cranial injury than females (P = 0.009). We conclude
      that the injuries received by Samnite male farmer-warriors occurred while
      defending pastoral-agricultural resources. Trauma rates are similar for some Iron
      Age populations and not for others. Behavior associated with violence during the
      Iron Age period can not be generalized for all populations found in Italy.

PMID- 16883567
TI  - How important are affiliation and cooperation? A reply to Sussman et al.

PMID- 16883568
TI  - Polyamines, PI(4,5)P2, and actin polymerization.
AB  - Spermine (SPM) and spermidine (SPD) activate isolated phosphatidylinositol-4
      phosphate 5-kinases (PI(4)P5K), enzymes that convert phosphatidylinositol-4
      phosphate to phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2). PI(4,5)P2
      formation is known to be involved in cellular actin reorganization and motility,
      functions that are also influenced by polyamines. It has not been proven that
      endogenous polyamines can control inositol phospholipid metabolism. We evoked
      large decreases in SPD and putrescine (PUT) contents in HL60 cells, using the
      ornithine decarboxylase inhibitor, alpha-difluoromethylornithine (DFMO), which
      resulted in decreases in PI(4,5)P2 content per cell and inositol phosphate
      formation to 76.9 +/- 3.5% and 81.5 +/- 4.0% of control, respectively. Accurately
      reversing DFMO-evoked decreases in SPD content by incubating cells with exogenous
      SPD for 20 min rescued these decreases. DFMO treatment and SPD rescues also
      changed the ratio of total cellular PI(4,5)P2 to PIP suggesting involvement of a
      SPD-sensitive PI(4)P5K. PUT and SPM were not involved in DFMO-evoked changes in
      cellular PI(4,5)P2 contents. In DFMO-treated HL60 cells, the percent of total
      actin content that was filamentous was decreased to 59.1 +/- 5.8% of that
      measured in paired control HL60 cells, a finding that was rescued following
      reversal of DFMO-evoked decreases in SPD and PI(4,5)P2 contents. In slowly
      proliferating DMSO-differentiated HL60 cells, inositol phospholipid metabolism
      was uncoupled from SPD control. We conclude: in rapidly proliferating HL60 cells,
      but not in slowly proliferating differentiated HL60 cells, there are endogenous
      SPD-sensitive PI(4,5)P2 pools, probably formed via SPD-sensitive PI(4)P5K, that
      likely control actin polymerization.

PMID- 16883569
TI  - Formation of elongated giant mitochondria in DFO-induced cellular senescence:
      involvement of enhanced fusion process through modulation of Fis1.
AB  - Enlarged or giant mitochondria have often been documented in aged tissues
      although their role and underlying mechanism remain unclear. We report here how
      highly elongated giant mitochondria are formed in and related to the senescent
      arrest. The mitochondrial morphology was progressively changed to a highly
      elongated form during deferoxamine (DFO)-induced senescent arrest of Chang cells,
      accompanied by increase of intracellular ROS level and decrease of mtDNA content.
      Interestingly, under exposure to subcytotoxic doses of H2O2 (200 microM), about
      65% of Chang cells harbored elongated mitochondria with senescent phenotypes
      whereas ethidium bromide (EtBr) (50 ng/ml) only reformed the cristae structure.
      Elongated giant mitochondria were also observed in TGF beta1- or H2O2-induced
      senescent Mv1Lu cells and in old human diploid fibroblasts (HDFs). In all
      senescent progresses employed in this study Fis1 protein, a mitochondrial fission
      modulator, was commonly downexpressed. Overexpression of YFP-Fis1 reversed both
      mitochondrial elongation and appearance of senescent phenotypes induced by DFO,
      implying its critical involvement in the arrest. Finally, we found that direct
      induction of mitochondrial elongation by blocking mitochondrial fission process
      with Fis1-DeltaTM or Drp1-K38A was sufficient to develop senescent phenotypes
      with increased ROS production. These data suggest that mitochondrial elongation
      may play an important role as a mediator in stress-induced premature senescence.

PMID- 16883570
TI  - Functional characterization of PKDREJ, a male germ cell-restricted polycystin.
AB  - Polycystin-1 regulates a number of cellular processes through the formation of
      complexes with the polycystin-2 ion channel or with other signal transduction
      proteins. Polycystin-1 is expressed in many tissues but other members of this
      gene family are distributed in a more restricted fashion. PKDREJ expression has
      been detected only in the mammalian testis, where it is restricted to the
      spermatogenic lineage and retained in mature sperm. However, the functional
      characteristics of this protein and its role in sperm biology are not well
      understood. In this study it is shown that PKDREJ can modulate G protein
      signaling and associates with several members of the polycystin-2 family. These
      interactions, as well as polycystin-2 association with TRPC channels, are
      consistent with a role of this protein in the regulation of the acrosome reaction
      and in other aspects of sperm physiology.

PMID- 16883571
TI  - Raf-1 signaling is required for the later stages of 1,25-dihydroxyvitamin D3
      induced differentiation of HL60 cells but is not mediated by the MEK/ERK module.
AB  - We are interested in determining the signaling pathways for 1,25-dihydroxyvitamin
      D3 (1,25D)-induced differentiation of HL60 leukemic cells. One possible candidate
      is Raf-1, which is known to signal cell proliferation and neoplastic
      transformation through MEK, ERK, and downstream targets. It can also participate
      in the regulation of cell survival and various forms of cell differentiation,
      though the precise pathways are less well delineated. Here we report that Raf-1
      has a role in monocytic differentiation of human myeloid leukemia HL60, which is
      not mediated by MEK and ERK, but likely by direct interaction with p90RSK.
      Specifically, we show that Raf-1 and p90RSK are increasingly activated in the
      later stages of differentiation of HL60 cells, at the same time as activation of
      MEK and ERK is decreasing. Transfection of a wild-type Raf-1 construct enhances
      1,25D-induced differentiation, while antisense Raf-1 or short interfering (si)
      Raf-1 reduces 1,25D-induced differentiation. In contrast, antisense
      oligodeoxynucleotides (ODN) and siRNAs to MEK or ERK have no detectable effect on
      differentiation. In late stage differentiating cells Raf-1 and p90RSK are found
      as a complex, and inhibition of Raf-1, but not MEK or ERK expression reduces the
      levels of phosphorylated p90 RSK. These findings support the thesis that Raf-1
      signals cell proliferation and cell differentiation through different
      intermediary proteins.

PMID- 16883572
TI  - The macrophage heterogeneity: difference between mouse peritoneal exudate and
      splenic F4/80+ macrophages.
AB  - Macrophages isolated from various tissues manifest differences in cell shape, the
      expression of surface markers, as well as metabolic and functional activities.
      However, the heterogeneity of macrophages expressing the same marker in different
      tissues has not been fully addressed. In the present study, mouse F4/80+
      peritoneal exudate macrophages (PEMs) and splenic macrophages (SPMs) appeared
      similar in most respects. But the percentages of cells expressing CD80, CD40, MHC
      II, TLR2, or TLR4, but not CD11c, CD54, or CD23, in freshly isolated F4/80+ SPMs
      were significantly higher than those in PEMs, whereas the levels of CD86+ cells
      in F4/80+ SPMs were markedly lower than those in PEMs. After lipopolysaccharide
      (LPS) stimulation, F4/80+ SPMs expressed significantly higher levels of CD86,
      CD40, or MHC-II than F4/80+ PEMs, but not CD11c, CD80, CD54, or CD23. F4/80+ SPMs
      had remarkably lower non-opsonic phagocytotic capacity against chicken RBCs or
      allo-T cells than PEMs as determined by two-photon microscopes and flow
      cytometry. SPMs produced markedly more NO than PEMs when cultured with LPS or
      allo-T cells. Furthermore, SPMs exhibited stronger immunogenicity than PEMs, as
      determined by the ability to stimulate T cell proliferation, delayed type
      hypersensitivity, and IFN-gamma production. The data showed the differences
      between SPMs and PEMs with regard to the phenotypes, phagocytosis, and
      immunogenicity, which may offer important information for us to better understand
      the distinguished immune responses of macrophages in spleens and the peritoneal
      cavity.

PMID- 16883573
TI  - Roles of two types of anion channels in glutamate release from mouse astrocytes
      under ischemic or osmotic stress.
AB  - Astrocytes release glutamate upon hyperexcitation in the normal brain, and in
      response to pathologic insults such as ischemia and trauma. In our experiments,
      both hypotonic and ischemic stimuli caused the release of glutamate from cultured
      mouse astrocytes, which occurred with little or no contribution of gap junction
      hemichannels, vesicle-mediated exocytosis, or reversed operation of the Na
      dependent glutamate transporter. Cell swelling and chemical ischemia activated,
      in cell-attached membrane patches, anionic channels with large unitary
      conductance (approximately 400 pS) and inactivation kinetics at potentials more
      positive than +20 mV or more negative than -20 mV. These properties are different
      from those of volume-sensitive outwardly rectifying (VSOR) Cl- channels, which
      were also expressed in these cells and exhibited intermediate unitary conductance
      (approximately 80 pS) and inactivation kinetics at large positive potentials of
      more than +40 mV. Both maxi-anion channels and VSOR Cl- channels were permeable
      to glutamate with permeability ratios of glutamate to chloride of 0.21 +/- 0.07
      and 0.15 +/- 0.01, respectively. However, the release of glutamate was
      significantly more sensitive to Gd3+, a blocker of maxi-anion channels, than to
      phloretin, a blocker of VSOR Cl- channels. We conclude that these two channels
      jointly represent a major conductive pathway for the release of glutamate from
      swollen and ischemia-challenged astrocytes, with the contribution of maxi-anion
      channels being predominant.

PMID- 16883574
TI  - Altered promoter usage characterizes monoallelic transcription arising with ERBB2
      amplification in human breast cancers.
AB  - Analysis of a collection of human breast cancers (n = 150), enriched in ERBB2
      positive cases (n = 57) and involving tumor genotyping relative to population
      matched blood genotyping (n = 749) for a common ERBB2 single nucleotide
      polymorphism Ala(G)1170Pro(C), revealed that ERBB2 amplification in breast cancer
      is invariably monoallelic. Analysis of paired breast cancer and blood samples
      from informative (G1170C heterozygotic) ERBB2-positive (n = 12) and ERBB2
      negative (n = 17) cases not only confirmed monoallelic amplification and ERBB2
      transcriptional overexpression but also revealed that most low ERBB2 expressing
      breast cancers (12/17) exhibit unbalanced allelic transcription, showing 3-fold
      to nearly 5,000-fold preferential expression from one of two inherited alleles.
      To explore cis-acting transcriptional mechanisms potentially selected during
      ERBB2 amplification, levels of four different ERBB2 transcript variants (5.2,
      4.7, 2.1, and 1.4 kb) were correlated with total (4.6 kb) ERBB2 mRNA levels in
      ERBB2-positive (n = 14) versus ERBB2-negative (n = 43) primary breast cancers.
      Relative expression of only the 2.1 kb extracellular domain-encoding splice
      variant and a 4.7 kb mRNA variant that uses an alternative start site were
      significantly increased in association with ERBB2-positivity, implicating altered
      promoter usage and selective transcript regulation within the ERBB2 amplicon.
      Altogether, these findings provide new mechanistic insights into the development
      of ERBB2-positive breast cancer and strong rationale for delineating candidate
      cis-acting regulatory elements that may link allele-specific ERBB2 transcription
      in premalignant breast epithelia with subsequent development of breast cancers
      bearing monoallelic ERBB2 amplicons.

PMID- 16883575
TI  - hERG1 channels in human esophagus: evidence for their aberrant expression in the
      malignant progression of Barrett's esophagus.
AB  - Ion channels regulate a broad range of cellular activities. Alteration in ion
      channel function has been reported in different human pathologies, such as
      cardiac, neuromuscular, autoimmune diseases, and cancer. We investigated the
      expression of hERG1 K+ channels in the human upper gastrointestinal tract,
      focusing our attention on the lower esophagus. In particular, we analyzed by both
      Reverse transcription and polymerase chain reaction (RT-PCR) and
      immunohistochemistry (IHC) endoscopic samples obtained from normal subjects, from
      patients suffering from gastroesophageal reflux, associated or not with
      esophagitis, and from patients affected by Barrett's esophagus (BE), that is,
      intestinal metaplasia. None of the normal samples, nor those from patients with
      gastro-esophageal reflux symptoms and reflux esophagitis expressed the hERG1
      protein. On the other hand, 69% of patients with BE expressed hERG1. Since BE is
      a preneoplastic lesion, dysplasias (Ds) and adenocarcinomas (ADKs) arising on a
      previously diagnosed BE were also analyzed, and all the samples showed a high
      expression of the hERG1 protein. The surveillance of patients with BE showed that
      89% of those who later developed ADKs displayed hERG1 expression. Data here
      reported, support the hypothesis that hERG1 expression marks an early step of the
      progression of normality to cancer in the human esophagus through a metaplastic
      and dysplastic stage.

PMID- 16883576
TI  - A downstream kinase of the mammalian target of rapamycin, p70S6K1, regulates
      human double minute 2 protein phosphorylation and stability.
AB  - Human double minute 2 (HDM2) is an oncoprotein overexpressed in many human
      cancers. HDM2 expression is regulated at multiple levels in cells.
      Phosphorylation of HDM2 plays an important role in its post-translational
      regulation. In this study, we have shown that the phosphatidylinositol 3-kinase
      (PI3K) inhibitor, LY294002, and the mammalian target of rapamycin (mTOR)
      inhibitor, rapamycin, have similar effects on the inhibition of HDM2
      phosphorylation and protein turnover. Rapamycin inhibited p70S6K1, but not AKT
      activation, indicating that rapamycin affects HDM2 phosphorylation via an AKT
      independent mechanism. Rapamycin also decreased HDM2 protein stability. Knockdown
      of p70S6K1 by a p70S6K1 siRNA resulted in the inhibition of HDM2 phosphorylation
      and a decrease in HDM2 protein turnover. Overexpression of p70S6K1 enhanced HDM2
      phosphorylation and led to an increase in HDM2 protein turnover. Our results
      suggest that p70S6K1 regulates turnover of HDM2 protein for cancer development.

PMID- 16883577
TI  - Myostatin induces cachexia by activating the ubiquitin proteolytic system through
      an NF-kappaB-independent, FoxO1-dependent mechanism.
AB  - Myostatin, a transforming growth factor-beta (TGF-beta) super-family member, has
      been well characterized as a negative regulator of muscle growth and development.
      Myostatin has been implicated in several forms of muscle wasting including the
      severe cachexia observed as a result of conditions such as AIDS and liver
      cirrhosis. Here we show that Myostatin induces cachexia by a mechanism
      independent of NF-kappaB. Myostatin treatment resulted in a reduction in both
      myotube number and size in vitro, as well as a loss in body mass in vivo.
      Furthermore, the expression of the myogenic genes myoD and pax3 was reduced,
      while NF-kappaB (the p65 subunit) localization and expression remained unchanged.
      In addition, promoter analysis has confirmed Myostatin inhibition of myoD and
      pax3. An increase in the expression of genes involved in ubiquitin-mediated
      proteolysis is observed during many forms of muscle wasting. Hence we analyzed
      the effect of Myostatin treatment on proteolytic gene expression. The ubiquitin
      associated genes atrogin-1, MuRF-1, and E214k were upregulated following
      Myostatin treatment. We analyzed how Myostatin may be signaling to induce
      cachexia. Myostatin signaling reversed the IGF-1/PI3K/AKT hypertrophy pathway by
      inhibiting AKT phosphorylation thereby increasing the levels of active FoxO1,
      allowing for increased expression of atrophy-related genes. Therefore, our
      results suggest that Myostatin induces cachexia through an NF-kappaB-independent
      mechanism. Furthermore, increased Myostatin levels appear to antagonize
      hypertrophy signaling through regulation of the AKT-FoxO1 pathway.

PMID- 16883579
TI  - An unusual extended DNA loop attachment region is located in the human dystrophin
      gene.
AB  - We have found and characterized an unusual extended area of DNA association with
      the nuclear matrix in the human dystrophin gene. This extended DNA loop anchorage
      region (LAR) has been mapped and characterized using a variety of biochemical and
      microscopy techniques. It spans approximately 200 kbp at chromosomal locations
      950-1,150 Kb downstream to the beginning of the first exon of the dystrophin gene
      Dp427m and covers a part of the intron 43, exon 44, and most of intron 44. The
      extended LAR harbors the major recombination hot spot of the dystrophin gene and
      a replication origin. We propose a model where DNA topoisomerase II-mediated
      cleavage at the nuclear matrix may enhance recombination events within this
      extended LAR.

PMID- 16883578
TI  - Loss of Kv and MaxiK currents associated with increased MRP1 expression in small
      cell lung carcinoma.
AB  - Regulatory volume decrease and exocrine secretion studies suggest a functional
      relationship between K+ and organic anion efflux. To test the hypothesis that the
      expression of K+ channels and MRP1 is reciprocally related, we employed the patch
      clamp and RT-PCR techniques on weakly (H69) and strongly MRP1-expressing (H69AR)
      small cell lung cancer cells. H69AR cells do not express the time- and voltage
      dependent delayed rectifying K+ current (Kv) reported earlier in H69 cells and
      confirmed here. About 80% of the Kv current in H69 cells inactivated at 0 mV,
      allowing us to identify other K+ currents present in these cells. Whole-cell
      currents from cells dialyzed and bathed in K-gluconate as the major ions
      exhibited inward rectification in both cell types. Inwardly rectifying (Kir)
      currents in both H69 and H69AR cells showed time-dependent activation and slow
      inactivation at large negative potentials. H69 cells also express a threefold
      larger Ca2+ -stimulated K+ -selective and iberiotoxin-sensitive current relative
      to H69AR cells. In excised inside-out patches exposed to 145 mM symmetrical K+
      solutions, H69 cells expressed a voltage- and Ca2+ -sensitive large conductance
      (128 +/- 5 pS) K+ channel (MaxiK). MaxiK-like currents were not observed at the
      whole-cell or single-channel level in H69AR cells. RT-PCR identified MaxiKalpha
      transcripts in H69 but not H69AR cells. These results indicate that two K+
      currents (MaxiK and Kv) and the organic anion transporter MRP1 are reciprocally
      expressed in H69 and H69AR cells.

PMID- 16883580
TI  - Stat5 in the mammary gland: controlling normal development and cancer.
AB  - The signal transducer and activator of transcription (Stat5) funnels
      extracellular signals of cytokines, hormones, and growth factors into
      transcriptional activity in the mammary gland. Postnatal development and
      functionality of this tissue is synchronized with the reproductive cycle.
      Consequently, Stat5 involvement in lobuloalveolar development, milk-protein
      synthesis, or tissue remodeling is dictated by the particular reproductive stage.
      Latent deregulation of Stat5 activity during the reproductive cycle predisposes
      the tissue to tumorigenesis at a later stage, when the female is no longer
      fertile. Accumulating data from studies with mouse models and breast-cancer
      specimens demonstrate a dual role for Stat5 in this context. It causes
      tumorigenesis, but delays metastasis progression. Consequently, Stat5 activity in
      breast-cancer specimens marks a better prognosis for survival.

PMID- 16883581
TI  - Activated hepatic stellate cells induce tumor progression of neoplastic
      hepatocytes in a TGF-beta dependent fashion.
AB  - The development of hepatocellular carcinomas from malignant hepatocytes is
      frequently associated with intra- and peritumoral accumulation of connective
      tissue arising from activated hepatic stellate cells. For both tumorigenesis and
      hepatic fibrogenesis, transforming growth factor (TGF)-beta signaling executes
      key roles and therefore is considered as a hallmark of these pathological events.
      By employing cellular transplantation we show that the interaction of neoplastic
      MIM-R hepatocytes with the tumor microenvironment, containing either activated
      hepatic stellate cells (M1-4HSCs) or myofibroblasts derived thereof (M-HTs),
      induces progression in malignancy. Cotransplantation of MIM-R hepatocytes with M
      HTs yielded strongest MIM-R generated tumor formation accompanied by nuclear
      localization of Smad2/3 as well as of beta-catenin. Genetic interference with TGF
      beta signaling by gain of antagonistic Smad7 in MIM-R hepatocytes diminished
      epithelial dedifferentiation and tumor progression upon interaction with M1-4HSCs
      or M-HTs. Further analysis showed that tumors harboring disrupted Smad signaling
      are devoid of nuclear beta-catenin accumulation, indicating a crosstalk between
      TGF-beta and beta-catenin signaling. Together, these data demonstrate that
      activated HSCs and myofibroblasts directly govern hepatocarcinogenesis in a TGF
      beta dependent fashion by inducing autocrine TGF-beta signaling and nuclear beta
      catenin accumulation in neoplastic hepatocytes. These results indicate that
      intervention with TGF-beta signaling is highly promising in liver cancer therapy.

PMID- 16883582
TI  - Immortalized cell lines from mouse xiphisternum preserve chondrocyte phenotype.
AB  - Chondrocytes are unique to cartilage and the study of these cells in vitro is
      important for advancing our understanding of the role of these cells in normal
      homeostasis and disease including osteoarthritis (OA). As there are limitations
      to the culture of primary chondrocytes, cell lines have been developed to
      overcome some of these obstacles. In this study, we developed a procedure to
      immortalize and characterize chondrocyte cell lines from mouse xiphisternum. The
      cells displayed a polygonal to fibroblastic morphology in monolayer culture. Gene
      expression studies using quantitative PCR showed that the cell lines responded to
      bone morphogenetic protein 2 (BMP-2) by increased expression of matrix molecules,
      aggrecan, and type II collagen together with transcriptional factor, Sox9.
      Stimulation by IL-1 results in the increased expression of catabolic effectors
      including MMP-13, nitric oxide synthase, ADAMTS4, and ADAMTS5. Cells cultured in
      alginate responded to BMP-2 by increased synthesis of proteoglycan (PG), a major
      matrix molecule of cartilage. IL-1 treatment of cells in alginate results in
      increased release of PG into the conditioned media. Further analysis of the media
      showed the presence of Aggrecanase-cleaved aggrecan fragments, a signature of
      matrix degradation. These results show that the xiphisternum chondrocyte cell
      lines preserve their chondrocyte phenotype cultured in either monolayer or 3
      dimensional alginate bead culture systems. In summary, this study describes the
      establishment of chondrocyte cell lines from the mouse xiphisternum that may be
      useful as a surrogate model system to understand chondrocyte biology and to shed
      light on the underlying mechanism of pathogenesis in OA.

PMID- 16883583
TI  - Glow discharge plasma treatment of polyethylene tubing with tetraglyme results in
      ultralow fibrinogen adsorption and greatly reduced platelet adhesion.
AB  - Previous studies from our lab have shown that fibrinogen adsorption (Gamma(Fg))
      must be reduced below 10 ng/cm(2) to significantly reduce platelet adhesion, and
      that radio frequency glow discharge (RFGD) treatment of polymeric films in the
      presence of tetraethylene glycol dimethyl ether (tetraglyme) can reduce Gamma(Fg)
      to the desired ultralow value. In this report, the effects of RFGD coatings of
      tetraglyme on the lumenal surface of PE tubing on Gamma(Fg) and on blood
      interactions both in vitro and ex vivo are described. Gamma(Fg) on the tetraglyme
      coated PE tubing was reduced to the desired ultralow level (<10 ng/cm(2)), and we
      also observed a significant decrease in adsorption of von Willebrand's factor. In
      vitro platelet adhesion from washed platelet suspensions, platelet rich plasma,
      or whole blood to tetraglyme-coated PE tubing was decreased compared to PE,
      polyurethane, or silicone rubber tubes. In addition, thrombin generation by
      platelets adherent to tetraglyme-coated PE was also much less than by platelets
      adherent to PE. When inserted in an ex vivo carotid artery-carotid artery shunt
      in sheep, the RFGD tetraglyme-coated PE exhibited a very low number of adherent
      platelets compared to heparin-coated, chromic acid-etched, or plain PE. The RFGD
      tetraglyme-coated PE tubes exhibited high protein and platelet resistance in
      vitro, and high platelet resistance ex vivo. The improved hemocompatibility is
      attributed to the unique chemical structure of RFGD tetraglyme that makes it
      highly protein resistant.

PMID- 16883584
TI  - Novel bioresorbabale composite fiber structures loaded with proteins for tissue
      regeneration applications: microstructure and protein release.
AB  - Novel bioresorbable core/shell composite fiber structures loaded with proteins
      were developed and studied. These unique polymeric structures are designed to
      combine good mechanical properties with a desired controlled protein-release
      profile, to serve as scaffolds for tissue regeneration applications. Core/shell
      fiber structures were formed by "coating" poly(L-lactic acid) fibers with protein
      containing poly(DL-lactic-co-glycolic acid) porous structures. Shell preparation
      (coating) was performed by the freeze-drying of water in oil emulsions. The
      present study focused on the effect of the emulsion's formulation on the porous
      shell structure and on the resulting cumulative protein release from the
      composite fibers for 90 days. Horseradish peroxidase (HRP) was used as the
      protein source. The release profiles usually exhibited an initial burst effect,
      accompanied by a decrease in release rate with time, as is typical for diffusion
      controlled systems. The HRP content and the emulsion's organic:aqueous phase
      ratio exhibited significant effects on both the shell microstructure and the HRP
      release profile from the composite fibers, whereas the polymer content of the
      emulsion's organic phase only affected these fiber characteristics in certain
      cases. Proper selection of the emulsion's parameters can yield core/shell fiber
      structures with the desired protein release behavior and other useful physical
      properties.

PMID- 16883585
TI  - Microsphere-based bioresorbable structures loaded with proteins for tissue
      regeneration applications.
AB  - Novel bioresorbable fiber/microsphere composite structures loaded with proteins
      were developed and studied. These unique polymeric structures are designed to
      combine good mechanical properties with a desired controlled protein-release
      profile, in order to serve as scaffolds for tissue regeneration applications. The
      composite fiber structures were formed by "coating" poly(L-lactic acid) fibers
      with protein-containing poly(DL-lactic-co-glycolic acid) microspheres. The
      microspheres were prepared by a double emulsion technique and were loaded with
      the model enzyme horseradish peroxidase (HRP). The present study focused on the
      effect of the double emulsion's composition and processing conditions on the
      microsphere structure and on the resulting cumulative protein release for 90
      days. The release profiles generally exhibited an initial burst effect, a lag
      period and an increased release rate after 2 months. HRP release from these
      structures was governed by diffusion, rather than by degradation. A decrease in
      the emulsion's mixing rate significantly improved the release profile through
      unique matrix-like structures. The initial burst effect can be reduced by
      decreasing the internal phase quantity and its protein content, or by adding a
      surfactant to the internal emulsion. Proper selection of the double emulsion
      formulation and processing conditions can yield fiber microsphere structures with
      the desired protein release behavior.

PMID- 16883586
TI  - Temperature-induced cell detachment on immobilized pluronic surface.
AB  - The Pluronic F68 and F127, a triblock copolymer of ethylene oxide and propylene
      oxide, was activated using carbonyldiimidazole (CDI), and CDI-activated Pluronic
      F68 and F127 was subsequently immobilized on the surface of a poly-L-lysine
      coated polystyrene tissue culture flask. Cell culture was performed on the
      Pluronic-immobilized flask. The morphology of fibroblasts (L929 cells) on the
      Pluronic F127-immobilized flask was mainly spherical, and showed less spreading
      behavior than that on the Pluronic F68-immobilized flask and conventional tissue
      culture flask. This observation indicates that L929 cells on Pluronic F127
      immobilized flasks were cultured in a bio-inert environment. L929 cells were
      successively detached from both Pluronic F127-immobilized flask and Pluronic F68
      immobilized flask by cooling the flask to 4-15 degrees C. This detachment is due
      to the hydration and dehydration properties of Pluronic, depending on the
      temperature. Umbilical cord blood was cultured in the Pluronic F127-immobilized
      and conventional polystyrene tissue culture flasks at 37 degrees C. The
      expression ratio of surface markers on hematopoietic stem cells (CD34 and CD133)
      cultured in the Pluronic F127-immobilized flask was significantly higher than
      that of the cells in polystyrene tissue culture flask.

PMID- 16883587
TI  - Decellularized placental matrices for adipose tissue engineering.
AB  - A tissue-engineered adipose substitute would be invaluable to plastic surgeons
      for reconstructive, corrective, and cosmetic procedures. This work involves the
      design of a scaffold for soft tissue augmentation incorporating the
      decellularized extracellular matrix (ECM) of human placenta. We have developed a
      protocol to decellularize an intact, large segment (8 cm by 8 cm) of the human
      placenta. To facilitate the complete decellularization of the dense matrix, a
      system was designed to perfuse the required chemicals into the placenta via the
      existing vasculature. Following processing, the original architecture of the
      placental ECM was preserved, including an intact vascular network. Histological,
      immunohistochemical, and scanning electron microscopic analyses confirmed the
      removal of the cells and cellular debris and characterized the composition and
      structure of the matrix. In vitro cell culture experimentation showed that the
      placental decellular matrix (PDM) could facilitate the adhesion of primary human
      adipose precursor cells at early time points. The PDM has great potential for use
      as a scaffold for adipose tissue engineering, as the placenta is a rich source of
      human ECM components that can be readily harvested without harm to the donor.

PMID- 16883589
TI  - Net expansion of dried demineralized dentin matrix produced by monomer/alcohol
      saturation and solvent evaporation.
AB  - The purpose of this work was to determine if nonaqueous methacrylate
      monomer/alcohol mixtures could expand dried collapsed demineralized dentin
      matrix. Thin disks (ca. 200 microm) of human dentin were demineralized and placed
      in wells beneath contact probes of linear variable differential transformers. The
      probes were placed on water-saturated expanded matrices to record the shrinkage
      associated with drying. Monomer mixtures containing hydroxyethyl methacrylate,
      2,2-bis[4-(2-hydroxy-3 methacryloyloxy)propoxyphenyl] propane, or
      triethyleneglycol dimethacrylate were mixed with methanol or ethanol at
      alcohol/monomer mass fraction % of 90/10, 70/30, 50/50, or 30/70. They were
      randomly applied to the dried matrices to determine the rate and magnitude of
      expansion; then shrinkage was recorded during evaporation of the alcohols. The
      results indicated that matrix expansion was positively correlated with the Hoy's
      solubility parameters for hydrogen bonding forces (delta(h)) of the
      monomer/solvent mixtures (p < 0.001). Expansions were more rapid with methanol
      containing than with ethanol-containing monomer mixtures. For the test solutions,
      triethyleneglycol dimethacrylate-containing mixtures produced the slowest rate of
      matrix expansion and hydroxyethyl methacrylate-containing mixtures the most rapid
      expansion. When the solvents were evaporated, the matrix shrank in proportion to
      the solvent content and the delta(h) of the monomer-solvent mixtures. The results
      indicate that expansion of dried, collapsed dentin matrices requires that the
      delta(h) of the mixtures be larger than 17 (J/cm(3))(1/2). The greater the
      delta(h) of the monomer solutions, the greater the rate and extent of expansion.

PMID- 16883590
TI  - Severe acute hypertriglyceridemia during acute lymphoblastic leukemia induction
      successfully treated with plasmapheresis.
AB  - Children suffering from Acute Lymphoblastic Leukaemia (ALL) treated with
      asparaginase and corticosteroids are at risk of developing severe lipid
      abnormalities. The authors report the case of a 10-year-old male with extremely
      high plasma triglyceride concentrations (4,000 mg/dl) during the induction phase
      of ALL associated with mild pancreatitis. Hypertriglyceridemia was successfully
      managed with plasmapheresis with a decrease in triglyceride levels to 590 mg/dl.
      Apheresis appears to be safe and effective in reducing hypertriglyceridemia and
      preventing related complications.

PMID- 16883593
TI  - Juvenile papillomatosis of the breast associated with neurofibromatosis 1.

PMID- 16883592
TI  - Prognostic significance of WT1 gene expression in pediatric acute myeloid
      leukemia.
AB  - BACKGROUND: The Wilms Tumor gene (WT1) encodes a transcription factor involved in
      kidney development and malignancy. WT1 expression in a subpopulation of early
      CD34+ cells has suggested its involvement in hematopoiesis. WT1 is aberrantly
      expressed in leukemias. High expression of WT1 at diagnosis has been associated
      with unfavorable prognosis in adult acute myeloid leukemia (AML). The prognostic
      relevance of WT1 expression in pediatric AML was evaluated in only one study,
      including 47 patients, which showed that very low levels of WT1 at presentation
      were associated with an excellent outcome. To test the validity of these findings
      we measured levels of WT1 in 41 newly diagnosed pediatric AML of the non-M3 FAB
      subtype. PROCEDURE: Patients were treated according to an AML-BFM 83-based
      protocol in a single institution. Mononucleated cells obtained from presentation
      BM aspirates were cryopreserved and later thawed and used for total RNA
      extraction and cDNA synthesis. The quantitative assessment of WT1 transcripts was
      made by real-time PCR (RQ-PCR). WT1 transcripts values were normalized with
      respect to the number of ABL transcripts. RESULTS: WT1 levels were significantly
      higher in patients bearing favorable chromosome abnormalities, t(8;21) and
      inv(16) (P = 0.002). Higher levels of WT1 expression were unexpectedly associated
      with a higher probability of overall survival by Cox regression analysis (P =
      0.002). Multivariate regression analysis could not discriminate between the
      effects of WT1 and cytogenetics on survival. CONCLUSIONS: Higher WT1 expression
      was associated with favorable cytogenetics subtypes and accordingly with better
      outcome in children with AML in this study.

PMID- 16883595
TI  - Identification and characterization of a sperm motility promoting glycoprotein
      from buffalo blood serum.
AB  - Early investigators reported the occurrence of unidentified protein factors in
      biological fluids that may regulate sperm motility essential for fertility
      potential. This study reports for the first time purification of a forward
      motility stimulating protein (FMSF-I), to apparent homogeneity, from a biological
      fluid (buffalo blood serum) and its characterization. FMSF-I is the major
      motility protein of buffalo serum: a rich source of the factor. FMSF showed high
      protein specificity and affinity for activating forward motility of goat cauda
      epididymal spermatozoa. The motility promoter at 0.5 microM level showed maximal
      activity when nearly 60%-70% of spermatozoa expressed forward motility. It is a
      66 kDa monomeric acidic protein rich in aspartate, glutamate, and leucine with
      isoelectric point of 3.7. FMSF: a Mg2+ -dependent protein binds to concanavalin A
      agarose and the glycoprotein nature of FMSF has been confirmed by PAS staining.
      The factor lost activity completely when treated with alpha-mannosidase showing
      that the sugar part of the protein is essential for its biological activity. FMSF
      has no species specificity for its motility-activating potential. Sperm surface
      has specific receptors of FMSF, which is strongly immunogenic. The factor is
      present in testis and epididymis although liver is its richest source. Motility
      promoting efficacy of FMSF is markedly higher than the well-known non-protein
      motility activators: theophylline and bicarbonate or their combination. FMSF is a
      physiological activator of sperm motility and as a slaughterhouse byproduct it
      has potentiality for solving some of the problems of animal breeding,
      conservation of endangered species, and human infertility: a global social
      problem.

PMID- 16883594
TI  - 2-Oxoglutarate downregulates expression of vascular endothelial growth factor and
      erythropoietin through decreasing hypoxia-inducible factor-1alpha and inhibits
      angiogenesis.
AB  - In oxygenated cells, hypoxia-inducible factor-1 (HIF-1) alpha subunits are
      rapidly degraded by a mechanism that involves ubiquitination by the von Hippel
      Lindau tumor suppressor E3 ligase complex using 2-oxoglutarate as a substrate. We
      examined the effect of 2-oxoglutarate on the production of erythropoietin and
      vascular endothelial growth factor (VEGF). The expression of erythropoietin and
      VEGF protein were dose-dependently downregulated in Hep3B cells by the addition
      of 2-oxoglutarate. The promoter activity of VEGF-luciferase was dose-dependently
      downregulated by the addition of 2-oxoglutarate. Gel mobility shift assays
      revealed that the addition of 2-oxoglutarate dose-dependently inhibited HIF-1
      binding activity, but did not affect GATA binding activity. Western blot analysis
      revealed that 2-oxoglutarate dose-dependently inhibited the HIF-1alpha protein
      level in Hep3B cells in hypoxic conditions. However, MG132 (the proteasome
      inhibitor) rescued the inhibition of HIF-1alpha protein expression by 2
      oxoglutarate. Furthermore, under hypoxic conditions, 2-oxoglutarate dose
      dependently inhibited tube formation in in vitro angiogenesis assays. These
      results indicate that 2-oxoglutarate treatment may be useful for the inhibition
      of angiogenesis.

PMID- 16883596
TI  - Constitutive expression of thrombospondin 1 in MC3T3-E1 osteoblastic cells
      inhibits mineralization.
AB  - Thrombospondin 1 (TSP1) is a multifunctional extracellular glycoprotein present
      mainly in the fetal and adult skeleton. Although an inhibitory effect of TSP1
      against pathological mineralization in cultured vascular pericytes has been
      shown, its involvement in physiological mineralization by osteoblasts is still
      unknown. To determine the role of TSP1 in biomineralization, mouse osteoblastic
      MC3T3-E1 cells were cultured in the presence of antisense phosphorothioate
      oligodeoxynucleotides complementary to the TSP1 sequence. The 18- and 24-mer
      antisense oligonucleotides caused concentration-dependent increases in the number
      of mineralized nodules, acid-soluble calcium deposition in the cell/matrix layer,
      and alkaline phosphatase activity within 9 days, without affecting cell
      proliferation. The corresponding sense or scrambled oligonucleotides did not
      affect these parameters. In the antisense oligonucleotide-treated MC3T3-E1 cells,
      thickened extracellular matrix, well-developed cell processes, increased
      intracellular organelles, and collagen fibril bundles were observed. On the other
      hand, the addition of TSP1 to the culture decreased the production of a
      mineralized matrix by MC3T3-E1 cells. Furthermore, MC3T3-E1 clones overexpressing
      mouse TSP1 were established and assayed for TSP1 protein and their capacity to
      mineralize. TSP1 dose-dependently inhibited mineralization by these cells both in
      vitro and in vivo. These results indicate that TSP1 functions as an inhibitory
      regulator of bone mineralization and matrix production by osteoblasts to sustain
      bone homeostasis.

PMID- 16883597
TI  - Ultrasound guided site specific gene delivery system using adenoviral vectors and
      commercial ultrasound contrast agents.
AB  - We have evaluated if ultrasound imaging (US) and various commercially available
      contrast microbubbles can serve as a non-invasive systemically administered
      delivery vehicle for site-specific adenoviral-mediated gene transfer in vitro and
      in vivo. The contrast agents were tested for their ability to enclose and to
      protect an adenoviral vector carrying the GFP marker gene (Ad-GFP) into the
      microbubbles. We have also evaluated the ability of the innate immune system to
      inactivate free adenoviruses as well as unenclosed viruses adsorbed on the
      surface of the contrast agents and in turn the ability of the microbubbles to
      enclose and to protect the viral vectors from such agents. In vitro as well as in
      vivo, innate components of the immune system were able to serve as inactivating
      agents to clear free viral particles and unenclosed adenoviruses adsorbed on the
      microbubbles' surface. Systemic delivery of Ad-GFP enclosed into microbubbles in
      the tail vein of nude mice resulted in specific targeting of the GFP transgene.
      Both fluorescence microscopy and GFP immunohistochemistry demonstrated US guided
      specific transduction in the targeted cells only, with no uptake in either heart,
      lungs or liver using complement-pretreated Ad-GFP microbubbles. This approach
      enhances target specificity of US microbubble destruction as a delivery vehicle
      for viral-mediated gene transfer.

PMID- 16883598
TI  - Apoptosis induced by troglitazone is both peroxisome proliferator-activated
      receptor-gamma- and ERK-dependent in human non-small lung cancer cells.
AB  - The role of the peroxisome proliferator-activated receptor-gamma (PPARgamma) in
      cell differentiation, cell-cycle arrest, and apoptosis has attracted increasing
      attention. We have recently demonstrated that PPARgamma ligands-troglitazone
      (TGZ) induced apoptosis in lung cancer cells. In this report, we further studied
      the role of ERK1/2 in lung cancer cells treated by TGZ. The result demonstrated
      that TGZ induced PPARgamma and ERK1/2 accumulation in the nucleus, in which the
      co-localization of both proteins was found. The activation of ERK1/2 resulted in
      apoptosis via a mitochondrial pathway. Both PPARgamma siRNA and U0126, a specific
      inhibitor of ERK1/2, were able to block these effects of TGZ, suggesting that
      apoptosis induced by TGZ was PPARgamma and ERK1/2 dependent. Inhibition of ERK1/2
      by U0126 also led to a significant decrease in the level of PPARgamma, indicating
      a positive cross-talk between PPARgamma and ERK1/2 or an auto-regulatory feedback
      mechanism to amplify the effect of ERK1/2 on cell growth arrest and apoptosis. In
      addition to ERK1/2, TGZ also activated Akt. Interestingly, inhibition of ERK1/2
      prevented the activation of Akt whereas the suppression of Akt had no effect on
      ERK1/2, suggesting that Akt was not necessary for TGZ-PPARgamma-ERK pathway.
      However, the inhibition of Akt promoted the release of cytochrome c, suggesting
      the activation of Akt may have a negative effect on apoptosis induced by TGZ. In
      conclusion, our study has demonstrated that TGZ, a synthetic PPARgamma ligand,
      induced apoptosis in NCI-H23 lung cancer cells via a mitochondrial pathway and
      this pathway was PPARgamma and ERK1/2 dependent.

PMID- 16883599
TI  - Treatment for children with severe aplastic anemia and sickle cell disease in low
      income countries in Latin America: a report on the recent meetings of the Monza
      International School of Pediatric Hematology/Oncology (MISPHO): Part III.
AB  - Treatment of hematologic disorders in low-income countries (LIC) is difficult.
      This report summarizes treatment of sickle cell disease and aplastic anemia by
      pediatric hematologists from 15 LIC who participate in the Monza International
      School of Pediatric Hematology/Oncology (MISPHO). Patients with severe sickle
      cell disease were treated with low dose hydroxyurea, which safely reduced vaso
      occlusive crises. Patients with severe aplastic anemia fared poorly due to lack
      of availability and high cost of anti-thymocyte globulin and cyclosporine and
      lack of access to stem cell transplantation. Appropriate therapy was most likely
      to occur in MISPHO centers with an active twinning program with a center in a
      high-income country.

PMID- 16883600
TI  - Protocol-based treatment for children with cancer in low income countries in
      Latin America: a report on the recent meetings of the Monza International School
      of Pediatric Hematology/Oncology (MISPHO)--part II.
AB  - Pediatric cancer programs in low-income countries (LIC) can improve outcomes.
      However, treatment must be tailored to the patient's living conditions and the
      availability of supportive care. In some cases, a more intense regimen will
      decrease survival since the increase in death from toxicity may exceed any
      decrease in relapse. Attempts to practice evidence-based pediatric oncology are
      thwarted by the lack of evidence derived from local experience in LIC to
      determine optimal therapy. This report summarizes treatment regimens used by
      pediatric oncologists from 15 countries of the Caribbean, Central and South
      America who participate in the Monza International School of Pediatric
      Hematology/Oncology (MISPHO). Patients with hepatoblastoma, Wilms tumor, and
      histiocytosis treated on unmodified published protocols had outcomes comparable
      to those in high-income countries (HIC). Those with rhabdomyosarcoma,
      osteosarcoma, Hodgkin lymphoma, and acute myeloid leukemia treated with
      unmodified regimens had event-free survival estimates 10%-20% lower than those
      reported in HIC due to higher rates of toxic death, abandonment of therapy, and
      relapse. Treatment of retinoblastoma is complicated by advanced stages and
      extraocular disease at diagnosis; improved outcomes depend on education of
      pediatricians and the public to recognize early signs of this disease. Use of
      unmodified protocols for Burkitt lymphoma and acute lymphoblastic leukemia have
      been associated with unacceptable toxicity in LIC, so MISPHO centers have
      modified published regimens by giving lower doses of methotrexate and reducing
      use of anthracyclines. Despite the use of all-trans-retinoic acid during
      induction for acute promyelocytic leukemia, the incidence of fatal hemorrhage
      remains unacceptably high.

PMID- 16883601
TI  - Improving outcomes for children with cancer in low-income countries in Latin
      America: a report on the recent meetings of the Monza International School of
      Pediatric Hematology/Oncology (MISPHO)-Part I.
AB  - The difference in survival for children diagnosed with cancer between high- and
      low-income countries (LIC) continues to widen as curative therapies are developed
      in the former but not implemented in the latter. In 1996, the Monza International
      School of Pediatric Hematology/Oncology (MISPHO) was founded in an attempt to
      narrow this survival gap. During its sixth and seventh meetings, members
      recognized the problem of lack of affordability of essential drugs to treat
      childhood cancer in many LIC, and initiated an advocacy program. In 1998, MISPHO
      spawned a collaboration of Central American pediatric oncology centers: the
      Asociacion de Hemato-Oncologia Pediatrica Centroamericana (AHOPCA). AHOPCA
      members reported preliminary findings from several of the 10 cooperative
      protocols that are currently in progress. In 2003, a second regional
      collaborative group was formed that includes seven centers in South America.
      Twinning programs between MISPHO centers and centers in high-income countries
      (HIC) have proven invaluable to harness the resources of these centers to improve
      pediatric oncology care in LIC. MISPHO educational efforts include oncology
      nursing, supportive care, cancer-specific updates, epidemiology, and clinical
      research methods. Educational efforts are facilitated by educational content and
      online conferencing via www.cure4kids.org. Identifying preventable causes of
      abandonment of therapy and documenting the nutritional status of patients treated
      at MISPHO centers are areas of active research.

PMID- 16883603
TI  - 1,25-dihydroxyvitamin D3 transcriptionally represses p45Skp2 expression via the
      Sp1 sites in human prostate cancer cells.
AB  - Upregulation of p27Kip1 protein in 1,25-dihydroxyvitamin D3-treated cancer cells
      is mediated via enhancement of gene transcription and reduction of protein
      degradation. 1,25-dihydroxyvitamin D3 inhibits the expression of p45Skp2, the F
      box protein which is implicated in p27Kip1 degradation, to reduce turnover of
      p27Kip1 protein. In this study, we elucidate the underlying mechanism by which
      1,25-dihydroxyvitamin D3 inhibits p45Skp2 in human LNCaP prostate cancer cells.
      Western blot and RT-PCR analysis suggest that 1,25-dihydroxyvitamin D3 suppresses
      p45Skp2 via transcriptional repression. Promoter activity assays indicate that
      1,25-dihydroxyvitamin D3 directly inhibits p45Skp2 promoter activity. Deletion
      analysis shows that 1,25-dihydroxyvitamin D3 response element is localized at 
      447/-291 bp region from the translational start site of the p45Skp2 promoter.
      Mutation analysis suggests that two Sp1 sites localized at -386/-380 and -309/
      294 bp region are required for transcriptional repression. Chromatin
      immunoprecipitation (CHIP) assay demonstrates that VDR indirectly binds to these
      Sp1 sites in vivo and this binding is increased after 1,25-dihydroxyvitamin D3
      treatment. Re-CHIP assay suggests that VDR and Sp1 form a complex to bind to the
      Sp1 sites. DNA affinity precipitation assay (DAPA) shows that histone deacetylase
      1 (HDAC1) is recruited to the Sp1 sites after 1,25-dihydroxyvitamin D3
      stimulation. Re-CHIP assay verifies that binding of Sp1 and HDAC1 to p45Skp2
      promoter is enhanced after 1,25-dihydroxyvitamin D3 treatment. HDAC inhibitor
      trichostatin A (TSA) reverses the inhibition of p45Skp2 promoter activity by 1,25
      dihydroxyvitamin D3. Collectively, our results suggest that 1,25-dihydroxyvitamin
      D3 induces the formation of VDR/Sp1 complex and acts via a Sp1- and HDAC1
      depedent pathway to inhibit p45Skp2 transcription.

PMID- 16883602
TI  - Biglycan binds to alpha- and gamma-sarcoglycan and regulates their expression
      during development.
AB  - The dystrophin-associated protein complex (DAPC), which links the cytoskeleton to
      the extracellular matrix, is essential for muscle cell survival, and is defective
      in a wide range of muscular dystrophies. The DAPC contains two transmembrane
      subcomplexes-the dystroglycans and the sarcoglycans. Although several
      extracellular binding partners have been identified for the dystroglycans, none
      have been described for the sarcoglycan subcomplex. Here we show that the small
      leucine-rich repeat (LRR) proteoglycan biglycan binds to alpha- and gamma
      sarcoglycan as judged by ligand blot overlay and co-immunoprecipitation assays.
      Our studies with biglycan-decorin chimeras show that alpha- and gamma-sarcoglycan
      bind to distinct sites on the polypeptide core of biglycan. Both biglycan
      proteoglycan as well as biglycan polypeptide lacking glycosaminoglycan (GAG) side
      chains are components of the dystrophin glycoprotein complex isolated from adult
      skeletal muscle membranes. Finally, our immunohistochemical and biochemical
      studies with biglycan null mice show that the expression of alpha- and gamma
      sarcoglycan is selectively reduced in muscle from young (P14-P21) animals, while
      levels in adult muscle (> or = P35) are unchanged. We conclude that biglycan is a
      ligand for two members of the sarcoglycan complex and regulates their expression
      at discrete developmental ages.

PMID- 16883604
TI  - Transforming growth factor-beta1 and bone morphogenetic protein-2 downregulate
      CaV3.1 channel expression in mouse C2C12 myoblasts.
AB  - In the developing skeletal muscle, fusion of myoblasts and myotube formation is a
      process that involves Ca2+ influx through T-type (CaV3) channels. Treatment of
      myoblasts with transforming growth factor-beta1 (TGF-beta1) and bone
      morphogenetic protein-2 (BMP-2) decreases the number of CaV3 channels in the
      plasma membrane and reduces myotube formation. In the current report, we examined
      whether the inhibitory actions of TGF-beta1 and BMP-2 involve alterations in CaV3
      mRNA expression in the myoblast C2C12 cell line. Using RT-PCR, we found that
      CaV3.1 but not CaV3.2 and CaV3.3 transcripts are present in either
      undifferentiated or fusion competent C2C12 myoblasts. Semi-quantitative analysis
      revealed a significant decrease of CaV3.1 mRNA expression in cells treated with
      TGF-beta1 and BMP-2. In contrast, patch-clamp recordings on HEK-293 cells stably
      expressing recombinant CaV3.1 channels showed that T-type currents were not
      affected by chronic exposure to the growth factors. These results suggest that
      muscle T-channel downregulation by TGF-beta1 and BMP-2 may be mediated by reduced
      transcription rather than through post-transcriptional modifications of CaV3.1
      channels.

PMID- 16883606
TI  - Being an effective chairman.

PMID- 16883605
TI  - Cyclic compression of chondrocytes modulates a purinergic calcium signalling
      pathway in a strain rate- and frequency-dependent manner.
AB  - Mechanical loading modulates cartilage homeostasis through the control of matrix
      synthesis and catabolism. However, the mechanotransduction pathways through which
      chondrocytes detect different loading conditions remain unclear. The present
      study investigated the influence of cyclic compression on intracellular Ca2+
      signalling using the well-characterised chondrocyte-agarose model. Cells labelled
      with Fluo4 were visualised using confocal microscopy following a period of 10
      cycles of compression between 0% and 10% strain. In unstrained agarose
      constructs, not subjected to cyclic compression, a subpopulation of approximately
      45% of chondrocytes exhibited spontaneous global Ca2+ transients with mean
      transient rise and fall times of 19.4 and 29.4 sec, respectively. Cyclic
      compression modulated global Ca2+ signalling by increasing the percentage of
      cells exhibiting Ca2+ transients (population modulation) and/or reducing the rise
      and fall times of these transients (transient shape modulation). The frequency
      and strain rate of compression differentially modulated these Ca2+ signalling
      characteristics providing a potential mechanism through which chondrocytes may
      distinguish between different loading conditions. Treatment with apyrase,
      gadolinium and the P2 receptor blockers, suramin and basilen blue, significantly
      reduced the percentage of cells exhibiting Ca2+ transients following cyclic
      compression, such that the mechanically induced upregulation of Ca2+ signalling
      was completely abolished. Thus cyclic compression appears to activate a
      purinergic pathway involving the release of ATP followed by the activation of P2
      receptors causing a combination of extracellular Ca2+ influx and intracellular
      Ca2+ release. Knowledge of this fundamental cartilage mechanotransduction pathway
      may lead to improved therapeutic strategies for the treatment of cartilage damage
      and disease.

PMID- 16883607
TI  - Internal mammary artery and vein: recipient vessels for free tissue transfer to
      the head and neck in the vessel-depleted neck.
AB  - BACKGROUND: Microvascular free tissue transfer is a standard reconstructive
      option for postablative defects of the head and neck. However, the success of
      this surgery requires suitable recipient vessels in the cervical region. This
      form of reconstruction can be particularly challenging in the vessel-depleted
      neck. While the internal mammary artery and vein (IMA/V) have been used
      extensively in breast reconstruction, there are few reports describing their use
      in head and neck reconstruction. We report the first case series of the use of
      the internal mammary vessels for head and neck microvascular reconstruction.
      METHODS: We reviewed 5 cases of free tissue transfers to the head and neck in
      which extensive prior treatment precluded the use of more traditional recipient
      vessels in the neck or upper chest. RESULTS: A variety of free flaps were
      transferred for different reconstructive problems which included: chin/lower lip
      (n = 2), closure of widely patent tracheoesophageal puncture sites (n = 2), and
      pharyngoesophageal reconstruction following staged repair of a severe stenosis (n
      = 1). The radial forearm free flap was transferred in 4 patients and the rectus
      abdominus free flap in 1 patient. The IMA/V on the right side was prepared in all
      cases. All free flaps were successfully revascularized without the need for vein
      grafts and without the need for any microvascular revision procedures.
      CONCLUSION: The internal mammary artery and vein provide reliable, easily
      accessible recipient vessels for microvascular reconstruction in the vessel
      depleted neck. The selection of free flap donor sites with long donor vessels
      facilitates the microvascular repair.

PMID- 16883608
TI  - Capacity to consent to research in schizophrenia: the expanding evidence base.
AB  - Capacity to consent to research, fundamental to informed consent and thus vital
      to the ethical conduct of research, may be impaired among a variety of research
      populations. Until recently, relatively little empirical evidence has been
      available to inform discussion and policy-making regarding whose capacity should
      be assessed, what should be measured, and how it should be measured. Capacity to
      consent to research has emerged as a central topic in the field of "empirical
      ethics," an important area of biomedical research devoted to bringing evidence
      based methods to the study of ethically salient issues in biomedical and
      biopsychosocial research. In this paper, empirical studies of capacity to consent
      to research are reviewed, with a particular focus on studies involving people
      with schizophrenia. These studies provide intriguing data regarding the nature,
      correlates, and modifiability of decisional abilities among potentially
      vulnerable research populations, including individuals with serious
      neuropsychiatric illnesses. Areas in need of further empirical ethics research
      are highlighted.

PMID- 16883609
TI  - Capacity to consent to or refuse treatment and/or research: theoretical
      considerations.
AB  - This article discusses theoretical dimensions of competency to consent to or
      refuse treatment and/or research. We will consider a number of issues. Our first
      subject is the nature of assessments of competency-their empirical, normative,
      and conceptual aspects. We then discuss how we should divide up the components of
      capacity-understanding, appreciation, reasoning, and evidencing a choice; how we
      should understand these different components; and whether all are indeed
      necessary. We discuss where to draw the line between capacity and incapacity on
      each of the four elements of capacity. We ask whether we should have a variable
      competency standard, either in general or in different contexts (e.g. treatment
      versus research). Finally we consider the role of mental illness in competency
      assessments.

PMID- 16883610
TI  - Capacity to consent: a snapshot of contemporary legal and clinical issues.
      Proceedings from a symposium, 2004.

PMID- 16883611
TI  - Decisional capacity in mental illness and substance use disorders: empirical
      database and policy implications.
AB  - Debates on decisional capacity in people with mental illnesses or substance use
      disorders have tended to be heated. Yet, they are often based not on empirical
      data but on personal opinions and experiences. The empirical database in this
      area is quite limited, but has been growing in recent years. The following
      discussion focuses on relevant clinical investigations. We consider variations
      across and within different diagnoses, barriers to decision-making, methods for
      assessing capacity-interview versus instruments, choosing from among different
      capacity instruments, decisional capacity-is it a state or a trait?, triggers for
      assessment of decisional capacity, methods for enhancing capacity, and decisional
      capacity in people with substance use disorders. Finally, we discuss some
      relevant health policy recommendations.

PMID- 16883612
TI  - Rotting with their rights on: why the criteria for ending commitment or restraint
      of liberty need not be the same as the criteria for initiating commitment or
      restraint of liberty, and how the restraint may sometimes justifiably continue
      after its prerequisites are no longer satisfied.
AB  - That coerced treatment must end when the criteria for initiating coerced
      treatment cease to apply appears to be universally accepted by courts and
      commentators.2 Moreover, the consensus appears to be justified by a steel-trap
      argument. If coercion is justified only when the patient is mentally ill and
      incapable, because then the patient lacks autonomous capacities, or lacks
      practical reasoning abilities that undercut autonomous capacities, then these
      justifications have no force when the patient either is not mentally ill or is
      capable. A parallel claim holds for civil commitment. This received wisdom, or in
      = out thesis, rests upon a conceptual confusion: a failure to distinguish the
      criteria for initiation of intervention, those for cessation of intervention, and
      the purpose of the commitment or coerced treatment. If the criteria for
      commitment were mental illness and dangerousness, and the criteria for release
      were the same, then the purpose of commitment would be to restore persons to the
      point where they are either just barely not mentally ill, or just barely not
      dangerous. That is a silly and self-defeating purpose for that large class of
      patients who, because of lack of insight, or otherwise, do not become treatment
      compliant until they are substantially healthier than being barely not mentally
      ill or barely not dangerous. It sets them up to become revolving-door patients.
      The purpose of commitment is rather to maximize the patient's mental health, and
      minimize her dangerousness without unduly burdening her liberty. If society is
      going to violate a patient's liberty, it should do so in a way that will resolve
      the problem that justified the restriction on liberty in the first place, so long
      as the restriction of liberty is not too great in relation to the expected gains
      from the intervention. The criteria for releasing a patient from commitment are
      in this way responsive to the purpose of the commitment. For some revolving-door
      patients, this entails that the criteria for their release from commitment should
      be stricter than the criteria for initiating commitment in the first place. The
      criteria for release from commitment for revolving-door patients should be that
      the criteria for initiation for commitment is not met plus it being more likely
      than not that the patient will be treatment compliant after release, assuming the
      additional restriction on liberty is less than the gains from the additional
      restraint, and the restriction is not unduly burdensome. Spelling this out, the
      criteria for release should be either not mentally ill, or else not dangerous, or
      capable, and more likely than not to be treatment compliant after release. For
      those patients for whom such a test is overly optimistic, we might substitute
      that there is a reasonable probability of treatment compliance after release, or
      that the probability of treatment compliance has been enhanced. These criteria
      are to be thought of as rough and ready rules of thumb, and not as analytically
      precise tests.

PMID- 16883613
TI  - Competency in the criminal context: an analysis of Robert Schopp's views.

PMID- 16883614
TI  - Steel traps and unattainable aspirations: a comment on Kress.

PMID- 16883615
TI  - Commentary on "TM and our models of informed consent" by Charles W. Lidz.

PMID- 16883616
TI  - Cognitive capacities of older adults who are asked to consent to medical
      treatment or to clinical research.
AB  - Knowledge about cognitive changes characteristically found in older adults
      provides necessary context for administering consent procedures. It should
      neither be assumed that most adults over a certain age are too demented to
      consent nor that decision-making is approached the same way by younger and older
      adults.

PMID- 16883617
TI  - The capacity to appoint a proxy and the possibility of concurrent proxy
      directives.
AB  - With the projected increase in the number of persons with dementia (who
      eventually lose their capacity to give informed consent to treatment and
      research), third-party decision-making will become even more common than it is
      today. We argue that, because there are situations in which an appointed proxy is
      preferred over a de facto surrogate, it is ethically important to understand the
      capacity of persons with dementia to delegate their decision-making authority
      regarding treatment and research decisions. In this paper, focusing mainly on the
      research consent context, we examine the idea that persons suffering from
      neurodegenerative disorders may retain significant abilities-including sufficient
      capacity for delegating one's authority for giving consent to research-even if
      they are not capable of giving independent consent themselves. We first propose a
      rationale for assessing the capacity to appoint a proxy and then describe a novel
      interview instrument for assessing the capacity to appoint a proxy for research
      consent.

PMID- 16883619
TI  - A therapeutic jurisprudence perspective on participation in research by subjects
      with reduced capacity to consent: a comment on Kim and Appelbaum.

PMID- 16883618
TI  - Can or should CAP be applied to child research subjects?: A comment on Kim and
      Appelbaum.

PMID- 16883620
TI  - Informed consent for schizophrenia research: what is an investigator (or IRB) to
      do?

PMID- 16883621
TI  - The therapeutic misconception and our models of competency and informed consent.
AB  - The doctrine of informed consent rests on empirical claims. This is true
      particularly of what commentators have characterized as the "strong" model of
      informed consent. This model assumes that if adequate information is given to a
      competent individual, understanding will result and, permitted to make a
      voluntary decision, the individual will make a rational decision. However, the
      "therapeutic misconception" posits that individuals may confuse the goals of
      research with those of treatment and may make decisions that do not rest on
      adequate understanding. This article reviews research suggesting that this may in
      fact be true, and concludes that, as a result, traditional notions of informed
      consent may not yield results consistent with the assumptions on which the
      doctrine of informed consent rests.

PMID- 16883622
TI  - Involuntary treatment and competence to proceed in the criminal process: capital
      and noncapital cases.
AB  - Recent cases raise a series of questions regarding the involuntary administration
      of treatment intended to restore or maintain competence to proceed in the
      criminal process. As is often the case, these matters take on a special urgency
      in the context of capital punishment. The analysis presented in this paper
      suggests that the relevant interests that courts should consider in deciding
      whether to order the involuntary administration of treatment to restore or
      maintain competence converge to a greater degree than one might initially expect.
      When the applicable conception of medical interests is appropriately defined and
      the state's interest in protecting the integrity of the process is given
      appropriate weight, the legally protected state and individual interests converge
      to a substantial degree. Protecting both sets of interests may require a variety
      of procedures designed to avoid misguided interventions with the potential to
      undermine both sets of interests. Finally, this analysis provides an approach
      that allows the courts to grant appropriate weight to the professional ethics of
      those who perform evaluations and deliver treatment in these contexts.

PMID- 16883623
TI  - Declining medical decision-making capacity in mild AD: a two-year longitudinal
      study.
AB  - This is a report of a two-year longitudinal study comparing healthy older adult
      subjects (n = 15) and mild Alzheimer's disease (AD) patients (n = 20) using an
      objective performance measure of medical decision-making capacity (MDC). Capacity
      to consent to medical treatment was measured using the Capacity to Consent to
      Treatment Instrument (CCTI). The CCTI is a psychometric measure that tests MDC
      using a series of four core capacity standards: S1 (evidencing/communicating
      choice), S3 (appreciating consequences), S4 (providing rational reasons), and S5
      (understanding treatment situation), and one experimental standard [S2] (making
      the reasonable treatment choice). For each standard, mild AD patients were
      assigned one of three capacity outcomes (capable, marginally capable, or
      incapable) based on cut-off scores derived from control group performance. At
      baseline, mild AD patients performed equivalently with controls on simple
      standards of evidencing a choice (S1) and making the reasonable choice ([S2]),
      but significantly below controls on complex standards of appreciation, reasoning,
      and understanding (S3, S4, and S5) (p < 0.02). Control performance was stable
      over time on all capacity standards. At one-year follow-up, the mild AD group did
      not show significant decline from baseline on any capacity standard. However, at
      two-year follow-up the mild AD group showed significant declines from baseline on
      the three complex standards (S3, S4, and S5) (p < 0.02), and a trend on one of
      the simple standards (S1). Over the two-year period, the proportion of marginally
      capable and incapable outcomes in the AD group increased substantially for four
      of the five standards (S1, S3, S4, and S5). Performance on [S2] remained stable
      over time in the AD group.We conclude that mild AD patients have impaired MDC at
      baseline, and demonstrate significant additional decline on complex consent
      abilities of appreciation, reasoning, and understanding over a two-year period.
      AD patients also show emerging impairment on the simple consent ability of
      evidencing choice at two-year follow-up. Capacity outcome data reflect similar
      declines over time for these four consent standards. The findings suggest the
      value of early assessment and regular monitoring at two-year intervals of MDC in
      patients with mild AD.

PMID- 16883624
TI  - Protective effect of L-carnitine on testicular ischaemia-reperfusion injury in
      rats.
AB  - Testicular torsion is a urological emergency referred to as 'acute scrotum',
      because inappropriate treatment can lead to male subfertility and infertility. A
      possible cause of testicular damage is the ischaemia-reperfusion (I/R) injury
      attributed to oxygen free radicals. L-carnitine, a vitamin-like antioxidant,
      plays a pivotal role in the maturation of spermatozoa within the reproductive
      tract. The aim of the present paper was to determine the protective effect of L
      carnitine on testicular I/R-induced injury. Thirty-two male rats were divided
      into 4 groups (n = 8). Testicular torsion was created by rotating the right
      testis 720 degrees in a clockwise direction. Group 1: sham-operated control;
      group 2: ischaemia; group 3: I/R; group 4: ischaemia-L-carnitine treatment
      reperfusion group. L-carnitine (500 mg kg(-1), intraperitoneally) was
      administered before 30 min of detorsion in Group 4. After torsion (5 h) and
      detorsion (5 h), bilateral orchidectomy was performed. The malondialdehyde (MDA)
      level was evaluated in testes. Histopathologically, Johnsen's spermatogenesis
      criteria and mean seminiferous tubule diameter (MSTD) measurements were used.
      Testicular MDA levels were higher in the torsion group compared to the sham
      control group (p < 0.05). Detorsion (reperfusion) caused a further increase in
      MDA levels (p < 0.05). Pretreatment with L-carnitine prevented a further increase
      in MDA levels (p < 0.05). Histologically, torsion caused some separation among
      germinal cells in the seminiferous tubules, which became much more prominent in
      the I/R group but was attenuated with L-carnitine pretreatment. In conclusion, L
      carnitine pretreatment may have a protective effect in experimental testicular
      torsion-detorsion model in rats by its well-known antioxidant potential.

PMID- 16883625
TI  - Vitreous Chemokines and Sho (Zheng in Chinese) of Chinese-Korean-Japanese
      medicine in patients with diabetic vitreoretinopathy.
AB  - We examined the levels of vitreous chemokines and Sho (Zheng in Chinese) of
      Chinese-Korean-Japanese medicine in diabetic patients. Patients undergoing
      vitrectomy were classified into Group 1 (no diabetic retinopathy), Group 2
      (diabetic retinopathy with no or a few new vessels), and Group 3 (diabetic
      retinopathy with many new vessels). The levels of IL-8, MCP-1, MIP-1alpha, MIP
      1beta, and RANTES in the vitreous fluid were measured using cytometric bead array
      method. Sho was determined by the standard diagnostic method of Chinese-Korean
      Japanese medicine. Vitreous levels of IL-8 and MCP-1 in Groups 2 and 3 were
      higher than those in Group 1. MIP-1alpha, MIP-1beta, and RANTES levels in Groups
      2 and 3 were almost the same as those in Group 1. The percentage of patients with
      Keishibukuryo-gan (Guizhifuling-wan in Chinese) sho in Group 3 was higher than
      that in Group 1. In conclusion, vitreous levels of IL-8 and MCP-1 were high in
      patients with diabetic vitreoretinopathy. Keishibukuryo-gan sho may be associated
      with diabetic vitreoretinopathy.

PMID- 16883626
TI  - Synergistic effect of ginger and nifedipine on human platelet aggregation: a
      study in hypertensive patients and normal volunteers.
AB  - In this study, we evaluated the synergistic effect of ginger and nifedipine on
      anti-platelet aggregation in normal human volunteers and hypertensive patients.
      The results showed that the percentage of platelet aggregation induced by
      collagen, ADP and epinephrine in hypertensive patients was larger than that in
      normal volunteers. Either aspirin or ginger could potentiate the anti-platelet
      aggregation effect of nifedipine in normal volunteer and hypertensive patients.
      These results suggested that ginger and nifedipine possessed synergistic effect
      on anti-platelet aggregation. A combination of 1 g ginger with 10 mg nifedipine
      per day could be valuable for cardiovascular and cerebrovascular complication due
      to platelet aggregation.

PMID- 16883627
TI  - Chunghyul-dan (Qingxie-dan) improves arterial stiffness in patients with
      increased baPWV.
AB  - Arterial stiffness is an important, independent determinant of cardiovascular
      risk. Pulse wave velocity (PWV) has been used as a valuable index of arterial
      stiffness and as a surrogate marker for atherosclerosis. Chunghyul-dan (CHD) has
      anti-hyperlipidemic activity, anti-inflammatory activity and anti-atherogenic
      effects. To determine its clinical effect on increased arterial stiffness, we
      examined whether CHD improves arterial stiffness in patients with increased
      brachial-ankle PWV (baPWV). Thirty-five subjects with increased baPWV (> 1400
      cm/sec) were recruited and randomized to a treatment group (20 subjects) or a
      control group (15 subjects). The treatment group was administered CHD at a dose
      of 600 mg three times a day for 8 weeks, and the control group received no
      medication (observation only). baPWV was assessed using a pulse pressure analyzer
      at baseline and after 8 weeks. Blood pressure and serum lipid profile were
      monitored in the treatment group. Our results indicate that baPWV was lowered
      significantly in the treatment group after 8 weeks of medication (p < 0.05), but
      not in the control group. Moreover, there were no significant changes in blood
      pressure and serum lipids profile except triglyceride level suggesting that the
      effect is largely independent of CHD's lipid-lowering effect or a blood pressure
      change. In conclusion, CHD appears to improve arterial stiffness in patients with
      increased PWV.

PMID- 16883628
TI  - Antinociceptive effects of heterotopic electroacupuncture in formalin-induced
      pain.
AB  - This study examined the antinociceptive effect of electroacupuncture (EA) to
      heterotopic acupoints on formalin-induced pain in rats. EA (2 ms, 10 Hz, and 3
      mA) was delivered to heterotopic acupoints HE(7) and PE(7), or non-acupoints at
      the right fore limb, for 30 min and was immediately followed by subcutaneous
      formalin injection into the left hind paw, respectively. The quantified pain
      score, electromyogram (EMG) response of the C-fiber reflex, and cFos
      immunoreactivity were assessed, respectively. EA to heterotopic acupoints
      significantly reduced both early- and late-phase pain-like behaviors and
      significantly decreased the EMG responses of the C-fiber reflex after formalin
      injection. By contrast, EA to non-acupoints had no significant effects on pain
      like behavior or the EMG response. In addition, EA to heterotopic acupoints
      decreased cFos immunoreactivity in the lumbar spinal dorsal horn. Therefore, EA
      induced pre-emptive antinociception via the extra-segmental inhibition of the
      formalin-induced pain, suggesting that EA to heterotopic acupoints is a useful
      treatment for inflammatory pain.

PMID- 16883629
TI  - Different patterns of pulse spectrum between survivors and non-survivors during
      progressive hemorrhage in rats.
AB  - Previous work from our laboratory has demonstrated that the percentage
      differences of 2nd (C2) and 3rd (C3) pulse harmonics related to Kidney and Spleen
      were both increased toward another steady state in rats after acute hemorrhage.
      Therefore, it is suggested that changes in pulse spectra might represent the
      ability of animals to survive a model of progressive hemorrhage. In this study,
      the difference of the pulse spectra patterns between survivors and non-survivors
      after progressive hemorrhage (by loss of 5%, 10% or 20% of the estimated blood
      volume) in anesthetized rats is determined. Seven rats, dead within 2 hours after
      a loss of 20% of the estimated blood volume hemorrhage, were defined as 'non
      survivors'. The other eleven rats, more than 2 hours after hemorrhage, were
      defined as 'survivors'. Pulse waves of arterial blood pressure before and after
      the hemorrhage were measured in parallel to the pulse spectrum analysis. Data
      among different phases were analyzed using one-way analysis of variance (ANOVA)
      with Duncan's test for pairwise comparisons. Differences between survivor and non
      survivor groups at each phase were analyzed using Student's t-test. A mixed
      effects linear regression model was applied to evaluate the relationship in
      harmonics, which significantly differed between the two groups. The study results
      showed that in rats, during progressive hemorrhage, the percentage differences of
      2nd harmonic proportion increased significantly; however, the result failed to
      show any significant difference between survivors and non-survivors. After the
      third blood withdrawal process, the percentage differences of 3rd harmonic
      proportion increased more significantly in the survivors. In addition, the
      percentage differences of 1st harmonic proportion related to the Liver for the
      survivor group was significantly lower than that of the non-survivors. After
      analysis with the mixed linear regression model, C3 and C1 demonstrated a linear
      regression relationship, and there existed significant differences between
      survivors and non-survivors. These results suggest that C3 might play an
      important role in physiology regarding surviving capability after progressive
      hemorrhage.

PMID- 16883630
TI  - Prevention of cerebral oxidative injury by post-ischemic intravenous
      administration of Shengmai San.
AB  - Shengmai San (SMS) is a traditional Chinese medicine (TCM) comprising three
      different herbal components, Panax ginseng, Ohiopogon japonicus and Fructus
      schisandrae and has been used for treating coronary heart diseases (Bensky and
      Barolet, 1990). It was shown that SMS effectively prevented cerebral oxidative
      injury in rats when it administered into the duodenum before cerebral ischemia
      reperfusion. In the present study, we examined whether post-ischemic
      administration of SMS can ameliorate cerebral ischemia-reperfusion injury in rats
      as well. Results showed that SMS injected immediately after ischemia also
      prevented the ischemia-reperfusion injury, when the effect was evaluated by the
      formation of protein carbonyl and thiobarbituric acid reactive substance (TBARS),
      and the loss of glutathione peroxidase (GPX). The preventative potential of SMS
      was decreased rapidly dependent on the time lag until SMS was injected after
      ischemia. However, it was noted that intravenously administered SMS protected the
      oxidative injury approximately 30% even after 60 min of reperfusion in terms of
      protein carbonyl formation. It is thus suggested that SMS injection might be
      useful for preventing the progression of injury in cerebral infarction after
      stroke.

PMID- 16883631
TI  - Effects of Safflower seed oil in osteoporosis induced-ovariectomized rats.
AB  - The effects of Korean Safflower (Carthamus tinctorius L) seed oil (SSO) on
      osteoporosis induced-ovariectomized rats were investigated. A total of 90 female
      Sprague-Dawley rats, 4-month-old, weighing 200-230 g were randomly assigned into
      3 groups (30 animals/group). The animals in group I were sham operated and those
      of group II and III were ovariectomized (Ovx). After eight weeks, the animals of
      group I and II received solvent vehicle daily, whereas those of group III were
      administered SSO orally (1 ml/kg) daily for 30 days. The changes in the serum
      levels of insulin-like growth factor-I (IGF-I), IGF-II, insulin-like growth
      factor binding protein-3 (IGBP-3), estrogen, total alkaline phosphatase (TALP),
      bone-specific alkaline phosphatase (BALP), calcium and phosphorous in serum, and
      also the histomorphology of the proximal tibia metaphysis and femur/body weight
      (F/B) ratio were examined in all the groups at every 10 days interval. Thirty
      days later, IGF-I, IGF-II, IGBP-3 and BALP levels were significantly increased (p
      < 0.05) in group III as compared to groups I and II. There were no significant
      differences in serum levels of estrogen, TALP and F/B ratio between groups II and
      III, but estrogen levels were higher in group I. These results suggest that the
      safflower seeds have possible roles in the improvement of osteoporosis induced
      ovariectomized rats.

PMID- 16883632
TI  - Shen-Fu attenuates endotoxin-induced acute lung injury in rats.
AB  - Sepsis is associated with the highest risk of progression to acute lung injury or
      acute respiratory distress syndrome. Shen-Fu has been advocated to treat many
      severely ill patients. Our study was designed to investigate the effect of Shen
      Fu on endotoxin-induced acute lung injury in vivo. Adult male Wistar rats were
      randomly divided into 6 groups: controls; those challenged with endotoxin (5
      mg/kg) and treated with saline; those challenged with endotoxin (5 mg/kg) and
      treated with Shen-Fu (1 mg/kg); those challenged with endotoxin (5 mg/kg) and
      treated with Shen-Fu (10 mg/kg); increase challenged with endotoxin (5 mg/kg) and
      treated with Shen-Fu (100 mg/kg); saline injected and treated with Shen-Fu (100
      mg/kg). TNF-alpha, IL-6, and NF-kappa B were investigated in the lung two hours
      later. Myeloperoxidase (MPO) activity and wet/dry weight ratio were investigated
      six hours later. Intravenous administration of endotoxin provoked significant
      lung injury, which was characterized by increment increase of MPO activity and
      wet/dry lung weight ratio, and TNF-alpha and IL-6 expression and NF-kappa B
      activation. Shen-Fu (10,100 mg/kg) decreased MPO activity and wet/dry weight
      ratio and inhibited TNF-alpha and IL-6 production, endotoxin-induced NF-kappa B
      activation. Our results indicated that Shen-Fu at a dose of higher than 10 mg/kg
      inhibited endotoxin-induced pulmonary inflammation in vivo.

PMID- 16883633
TI  - Effect of resveratrol on NF-kappaB activity in rat peritoneal macrophages.
AB  - This study was to investigate the inhibitive effect of resveratrol (RESV) on
      nuclear factor kappa B (NF-kappaB) expression and activity induced by
      lipopolysaccharide (LPS) in rat peritoneal macrophages (PMA). Male Sprague-Dawley
      (SD) rats were randomly divided into 7 groups, including control group, LPS group
      and RESV I-V group. In the LPS group, PMA were incubated in DMEM containing LPS
      (10 microg/ml), whereas in control group, PMA were incubated in DMEM only. In the
      RESV I-V groups, PMA were incubated in DMEM containing LPS (10 microg/ml) and
      different concentrations of RESV. After 24 hours of incubation, NF-kappaB
      activity in PMA, and the levels of tumor necrosis factor alpha (TNF-alpha),
      interleukin-1 (IL-1) and nitric oxide (NO) in the culture medium were measured.
      In the concentrations of 1.25-5 microg/ml, RESV had a dose- dependent inhibitive
      effect on NF-kappaB activity in PMA as well as the expressions of TNF-alpha, IL-1
      and NO in the culture medium contrasted with the LPS group. There was no
      significant difference in the levels of these pro-inflammatory factors between
      the groups of 5 microg/ml and 10 microg/ml RESV. In conclusion, RESV has the
      potential for the future application of preventing inflammatory diseases
      involving PMA.

PMID- 16883634
TI  - Immunomodulating effects of fractioned polysaccharides isolated from Yu-Ping-Feng
      Powder in cyclophosphamide-treated mice.
AB  - Yu-Ping-Feng-Powder (YP), a traditional Chinese medicine prescription, is widely
      applied in China for the cure and prevention of diseases related to
      immunodeficiency. To test whether the fractioned polysaccharides (YPF-P) isolated
      from YP have immunomodulating activities, the effects of YPF-P on
      cyclophosphamide (Cy)-treated mice were studied in relation to phagocytosis of
      macrophage, splenocyte proliferation, and humoral, and cellular immunity
      parameters. It was found that YPF-P enhances phagocytic activity, augments ConA-
      or LPS-stimulated T cell proliferation, increases the quantitative haemolysis of
      SRBC (QHS) and delayed-type hypersensitivity reaction (DTH) to
      dinitrofluorobenzene. Hence, YPF-P restored the immuno-competence suppressed by
      Cy. YPF-P also augmented IL-2 and IFN-gamma production, but failed to increase IL
      4 production, which indicates that there is high probability that it enhance Th1
      function. These results suggested that YPF-P has immunomodulating effects and
      that the polysaccharides constitute one of the active components of YP.

PMID- 16883635
TI  - Rubus coreanus Miq. extract promotes osteoblast differentiation and inhibits bone
      resorbing mediators in MC3T3-E1 cells.
AB  - To prevent bone loss that occurs with increasing age, certain nutritional and
      pharmacological factors are needed. In the present study, the ethanol extract
      from the fruit of Rubus coreanus Miq. (RCE) was investigated for its effect on
      the function of osteoblastic MC3T3-E1 cells. RCE (10approximately50 microg/ml)
      caused a significant elevation in cell viability, alkaline phosphatase (ALP)
      activity, collagen content, and osteocalcin secretion in the cells. The effect of
      RCE (50 microg/ml) in increasing cell viability, ALP activity, and collagen
      content was prevented by the presence of 10(-6) M cycloheximide and 10(-6) M
      tamoxifen, suggesting that RCE's effect results from a newly synthesized protein
      component and might be partly involved in estrogen action. We then examined the
      effect of RCE on the H(2)O(2)-induced apoptosis and production of local factors
      in osteoblasts. Treatment with RCE (10approximately50 microg/ml) decreased the
      0.2 mM H(2)O(2)-induced apoptosis and production of tumor necrosis factor (TNF)
      alpha, interleukin (IL)-6 and nitric oxide (NO) in osteoblasts. Our data indicate
      that the enhancement of osteoblast function by Rubus coreanus Miq. may result in
      the prevention of osteoporosis and inflammatory bone diseases.

PMID- 16883636
TI  - Endothelium-dependent induction of vasorelaxation by the butanol extract of
      Phellinus igniarius in isolated rat aorta.
AB  - The butanol extract of Phellinus igniarius (BPI) induced relaxation of the
      phenylephrin e-precontracted rat aorta in a dose-dependent manner, and its effect
      was abolished by the removal of functional endothelium. Pretreatment of the
      aortic tissues with N(G)-nitro-L-arginine methyl ester (L-NAME), methylene blue,
      or 1H-[1,2,4]-oxadiazole-[4,3-alpha]-quinoxalin1-one (ODQ) inhibited the vascular
      relaxation induced by BPI. BPI-induced vascular relaxations were also markedly
      attenuated by the addition of verapamil or diltiazem, while the relaxant effect
      of BPI was not blocked by pretreatment with indomethacine, glibenclamide,
      tetraethylammonium (TEA), atropine, or propranolol. Incubation of endothelium
      intact rat aorta with BPI increased the production of cGMP in a dose-dependent
      manner. These results suggest that BPI dilates vascular smooth muscle via
      endothelium-dependent nitric oxide-cGMP signaling pathway, with the possible
      involvement of L-type Ca(2+) channels.

PMID- 16883637
TI  - Morin promotes the production of Th2 cytokine by modulating bone marrow-derived
      dendritic cells.
AB  - Our previous studies had reported that morin decreased the interleukin-12 (IL-12)
      and tumor necrosis factor-alpha (TNF-alpha) production in lipopolysaccharide
      (LPS)-activated macrophages, suggesting that morin may promote helper T type 2
      (Th2) response in vivo. Dendritic cells (DCs) are the most potent antigen
      presenting cells and known to play a major role in the differentiation of helper
      T type 1 (Th1) and Th2 responses. This study aimed to reveal whether morin is
      able to control the Th differentiation through modulating the maturation and
      functions of DCs. Bone marrow-derived dendritic cells (BM-DCs) were incubated
      with various concentrations of morin and their characteristics were studied. The
      results indicated that morin significantly affects the phenotype and cytokine
      expression of BM-DCs. Morin reduced the production of IL-12 and TNF-alpha in BM
      DCs, in response to LPS stimulation. In addition, the proliferative response of
      stimulated alloreactive T cells was significantly decreased by morin in BM-DCs.
      Furthermore, allogeneic T cells secreted higher IL-4 and lower IFN-gamma in
      response to morin in BM-DCs. In conclusion, these results suggested that morin
      favors Th2 cell differentiation through modulating the maturation and function of
      BM-DCs.

PMID- 16883638
TI  - Effect of 3-Phenyl-2-Propene-1-ol on PGE2 release from rat cerebral microvascular
      endothelial cells stimulated by IL-1beta.
AB  - Fever, an elevation in body temperature, is thought to be terminally mediated by
      prostaglandin E(2) (PGE(2)). Both Guizhi Tang (GZT) and its active fraction A
      (Fr.A) showed an antipyretic effect in rats. 3-Phenyl-2-propene-1-ol was one of
      the active compounds isolated from Fr.A. In the present study, we examined the
      influence of interleukin-1beta (IL-1beta) on prostaglandin E(2) (PGE(2)) release,
      and the effect of 3-phenyl-2-propene-1-ol on IL-1beta-induced PGE(2) release from
      rat cerebral endothelial cells (rCMEC). Cultured rCMEC were used in the study. In
      vitro, cells express typical phenotypic markers of brain endothelium. Using a
      monoclonal antibody against von Willebrand factor, immunocytochemical analysis
      revealed positive immunoreactivity in the cytoplasm of cultured cells. rCMEC were
      incubated in M199 medium containing IL-1beta in the presence or absence of 3
      phenyl-2-propene-1-ol. After incubation, the conditioned media were collected and
      the amount of PGE(2) was measured by enzyme-linked immunosorbent assay (ELISA).
      IL-1beta increased the production of PGE(2) in a dose- and time-dependent manner.
      3-Phenyl-2-propene-1-ol significantly decreased IL-1beta-induced PGE(2) release
      in a dose-dependent manner. Our results indicate that 3-phenyl-2-propene-1-ol
      inhibits the PGE(2) release from rCMEC stimulated by IL-1beta, and may have an
      antipyretic effect.

PMID- 16883641
TI  - Keeping sight of the goal.

PMID- 16883639
TI  - Samul extract protects against the H2O2-induced apoptosis of H9c2 cardiomyoblasts
      via activation of extracellular regulated kinases (Erk) 1/2.
AB  - Samul extract, containing Radix Rehmanniae, Radix Angelicae Gigantis, Radix
      Paeoniae, and Rhizoma Cnidii, has been traditionally used for treatment of
      ischemic heart and brain damages in Oriental medicine. However, little is known
      about the mechanism by which Samul rescues cells from cytotoxic damage. This
      study was designed to investigate the protective mechanisms of Samul on H(2)O(2)
      induced death of H9c2 cells. Treatment with H(2)O(2) markedly decreased the
      viability of H9c2 cells in a dose- and time-dependent manner, which was
      significantly prevented by pre-treatment with Samul. The nature of death of H9c2
      cells by H(2)O(2) was demonstrated by apoptotic features, including ladder
      pattern fragmentation of genomic DNA and chromatin condensation, which were
      markedly abolished by pretreatment of Samul in H(2)O(2)-treated cells. We further
      demonstrated that MEK inhibitor, PD98059, dose-dependently attenuated the
      protective effects of Samul against H(2)O(2), whereas inhibitors of Jnk and p38
      did not. Consistently, Samul induced the early phosphorylation of Erk, p44, in
      H(2)O(2)-treated cells. In addition, treatment with Samul also resulted in an
      increase of expression of anti-apotogenic Bcl2 protein, which was decreased by
      H(2)O(2). However, it inhibited the expression of apotogenic Bax protein in
      H(2)O(2)-treated cells. Taken together, these results suggest that the protective
      effects of Samul against oxidative damage may be achieved via activation of MAP
      kinase, Erk as well as Bcl2 family proteins.

PMID- 16883640
TI  - Antioxidant properties of Glossogyne tenuifolia.
AB  - Glossogyne tenuifolia (Labill) Cass. (Compositae) is a special medicinal plant in
      the Pescadores Islands. Ethanolic, cold and hot water extracts were prepared from
      the dried herb and their antioxidant properties and components were studied.
      Ascorbic acid, alpha-tocopherol, butylated hydroxyanisole, citric and
      ethylenediaminetetraacetic acids were used in assays for comparison. With regard
      to EC(50) values in antioxidant activity, ethanolic and hot water extracts (0.08
      and 0.09 mg/ml) were much more effective than the cold water extract (0.76
      mg/ml). At 1.0 mg/ml, reducing capacities were 1.57, 0.31 and 1.04 for ethanolic,
      cold water and hot water extracts, respectively. Scavenging abilities on 1,1
      diphenyl-2-picrylhydrazyl radicals were in descending order: ethanolic > cold
      water > hot water extracts. At 20 mg/ml, the hot water extract chelated all
      hydroxyl ions (100%) whereas the scavenging ability of the cold water extract was
      68.86%. Chelating abilities on ferrous ions were in descending order: cold water
      > hot water > ethanolic extracts. Phenols were found to be the major antioxidant
      components. All EC(50) values were below 20 mg/ml, and some even below 0.1 mg/ml,
      indicating that all three extracts from G. tenuifolia were rich in antioxidant
      properties.

PMID- 16883642
TI  - Industry anger over stringent trial disclosure requirements.

PMID- 16883643
TI  - Safety concerns raised over RNA interference.

PMID- 16883644
TI  - Vaccines give written description guidance.

PMID- 16883645
TI  - Ubiquitin-proteasome system modulation.

PMID- 16883646
TI  - John A. Fraser.

PMID- 16883647
TI  - Biosimilars: initial excitement gives way to reality.

PMID- 16883648
TI  - Varenicline.

PMID- 16883649
TI  - Viewpoint: the way forward in cardiac imaging.

PMID- 16883650
TI  - Publishing cardiac surgeons' outcome data.

PMID- 16883651
TI  - Spotlight on a young cardiologist.

PMID- 16883652
TI  - Putting the fun into functional toxicogenomics.

PMID- 16883653
TI  - Sudden cardiac death associated with an extremely rare coronary anomaly of the
      left and right coronary arteries arising exclusively from the posterior
      (noncoronary) sinus of Valsalva.

PMID- 16883654
TI  - Turning Medicaid beneficiaries into purchasers of health care: critical success
      factors for Medicaid consumer-directed health purchasing.

PMID- 16883655
TI  - Neuroendocrine immune system involvement in rheumatology.

PMID- 16883656
TI  - [Family doctors and semFYC faced with tobacco dependency].

PMID- 16883657
TI  - Treatment options for refractory angina in patients who are not candidates for
      revascularization.
AB  - Patients with refractory angina are those for whom medical therapy has failed to
      eradicate the angina completely and who have persistent symptoms that are stable
      but limit their activities of daily living. Approach to management must include
      the elimination of the secondary causes of this condition and maximum medical
      therapy, and if angina persists, the consideration of other strategies.
      Controversy exists regarding the value of transmural myocardial laser
      revascularization. Enhanced external counterpulsation is clinically effective in
      approximately 70% of patients. Spinal cord stimulation is not being used
      clinically in the United States. In the United States, it is still an
      investigational procedure that is currently being evaluated prospectively in a
      randomized trial. Ranolazine, an inhibitor of sodium-dependent calcium overload,
      may prove to be useful in patients with refractory angina.

PMID- 16883658
TI  - [Rochus, patron saint of physicians and hospitals--a teledermatologic quiz].
AB  - The painting "St. Rochus with an angel" by Quinten Massys in the Alte Pinakothek
      in Munich was utilized for a teledermatological quiz. First, only a detail of the
      plague bubo on the thigh was sent electronically to all physicians in our
      department. The answers were correct descriptions, but the interpretations quite
      heterogeneous. In a second set, the full painting together with the hint-
      Pinakothek - was given. Now the number of descriptively correct diagnoses was
      high; one resident knew the name of the featured individual and his diagnosis.
      This example demonstrates one problem with teledermatology - when viewing a
      clinical picture, relevant additional information is frequently essential in
      order to make a correct diagnosis. In addition, this presentation of saint
      physicians and hospitals, the holy Rochus, better known to those who are under
      his protection.

PMID- 16883660
TI  - [On the 70th birthday of Professor Dr.med. Detlef Petzoldt].

PMID- 16883659
TI  - [Prof. Dr. med. Eva B. Brocker on her 60th birthday].

PMID- 16883661
TI  - [It's going well, readers!].

PMID- 16883662
TI  - [Anal carcinoma and anal intraepithelial neoplasia in HIV-infections].

PMID- 16883663
TI  - The most personal information of all: an appraisal of genetic privacy in the
      shadow of the Human Genome Project.
AB  - The advent of genetics and genetic testing has given rise to unique problems for
      the family. The discovery of a predisposition to a genetic condition in one
      individual also reveals information about the genetic make-up and potential risks
      of family members. There is, therefore, potential for conflict over access to and
      control of such information. Traditionally the duty of confidentiality owed by a
      health care professional to a patient has provided an appropriate means by which
      personal health information has been kept secured. It is not clear, however, that
      the problems which surrounds genetic information in the familial milieu can be
      adequately dealt with using confidentiality. This article examines these problems
      and argues for the value of an appeal to the concept of privacy in seeking to
      resolve some of the more intractable issues.

PMID- 16883665
TI  - [Multiple chemical sensitivity in sick-building syndrome].
AB  - The sick building syndrome includes irritation of the eyes and the respiratory
      tract neurotoxicity affectation and skin problems, which can occur in individuals
      under improperly ventilated buildings. Poor air quality, as shown in CO2
      atmospheric levels of more than 1,000 ppm, results in a pathological exposure to
      biological and chemical products. We present a work-related case of multiple
      chemical hypersensitivity from a dialysis unit that had no air renewal. This
      person, who was summitted to continuous exposure despite having taken corrective
      measures in the ventilation, developed chronic fatigue syndrome. An acoustic
      voice observation alerted of the case which led to the analysis of the
      environmental conditions which confirmed the relationship between multiple
      chemical hypersensitivity and chronic fatigue syndrome. This case stresses the
      neglected fact that all health service centres pose a high risk of chemical
      exposure and that there exists a lack of rigoroursness in putting in practice
      scientific medical knowledge.

PMID- 16883666
TI  - Advances in antithrombotic therapy in acute myocardial infarction: the ExTRACT
      TIMI 25 and OASIS-6 Trials.

PMID- 16883667
TI  - Adapting the JCAHO Protocol for perioperative quality care.

PMID- 16883668
TI  - Preparing for natural and man-made disasters.

PMID- 16883664
TI  - Economically important non-oncogenic immunosuppressive viral diseases of chicken-
      current status.
AB  - Immunosuppressive viral diseases threaten the poultry industry by causing heavy
      mortality and economic loss of production, often as a result of the chickens'
      increased susceptibility to secondary infections and sub-optimal response to
      vaccinations. This paper aimed to present an up-to-date review of three specific
      economically important non-oncogenic immunosuppressive viral diseases of
      chickens, viz. chicken infectious anaemia (CIA), infectious bursal disease (IBD)
      and hydropericardium syndrome (HPS), with emphasis on their immunosuppressive
      effects. CIA and IBD causes immunosuppression in chickens and the socio-economic
      significance of these diseases is considerable worldwide. CIA occurs following
      transovarian transmission of chicken anaemia virus and has potential for inducing
      immunosuppression alone or in combination with other infectious agents, and is
      characterized by generalized lymphoid atrophy, increased mortality and severe
      anemia. The virus replicates in erythroid and lymphoid progenitor cells, causing
      inapparent, sub-clinical infections that lead to depletion of these cells with
      consequent immunosuppressive effects. The IBD virus replicates extensively in
      IgM(+) cells of the bursa and chickens may die during the acute phase of the
      disease, although IBD virus-induced mortality is highly variable and depends,
      among other factors, upon the virulence of the virus strain. The sub-clinical
      form is more common than clinical IBD because of regular vaccination on breeding
      farms. Infection at an early age significantly compromises the humoral and local
      immune responses of chickens because of the direct effect of B cells or their
      precursors. HPS is a recently emerged immunosuppressive disease of 3-6-weeked
      broilers, characterized by sudden onset, high mortality, typical hydropericardium
      and enlarged mottled and friable livers, with intranuclear inclusion bodies in
      the hepatocytes. The agent, fowl adenovirus-4, causes immunosuppression by
      damaging lymphoid tissues; the presence of IBD and CIA viruses may predispose for
      HPS or HPS may predispose for other viral infections. Synergism with CIA or other
      virus infections or prior immunosuppression is necessary to produce IBH-HPS in
      chickens and the susceptibility of chickens infected with fowl adenovirus varies
      throughout the course of CIA infection. The mechanism of immunosuppression has
      been studied in detail for certain chicken viruses at molecular levels, which
      will provides new opportunities to control these diseases by vaccination.

PMID- 16883669
TI  - Intimate partner violence: continuing education for registered nurses.
AB  - Intimate partner violence, also known as domestic violence, is a leading health
      problem affecting approximately 50% of women during the course of their lifetime.
      A large percentage of the abusers also abuse their children and older adults.
      Nurses are in a key position to identify and intervene with victims of abuse.
      However, a major barrier to screening and referral is lack of education. Nurses
      indicate a lack of education in their formal undergraduate and graduate programs.
      Therefore, nurses should be introduced to this topic through a 2-hour continuing
      education program.

PMID- 16883670
TI  - Influence of registered nurses' attitudes toward bariatric patients on
      educational programming effectiveness.
AB  - BACKGROUND AND OBJECTIVE: This study describes registered nurses' (RNs')
      attitudes toward obese adult patients using the Attitudes Toward Obese Adult
      Patients Instrument. METHODS: Full-time RNs (N = 119) employed in a medical
      center, acute rehabilitation institution, and skilled nursing facility
      participated in the study. RESULTS: Findings revealed that RNs have positive
      attitudes toward obese adults. RNs were concerned about personal and patient
      safety. Respondents recognized the complex care needs of bariatric patients and
      the increased workload associated with meeting these demands. There were
      differences in attitudes between medical center RNs and acute rehabilitation RNs,
      possibly related to differences in workload and length of stay. CONCLUSIONS: The
      effectiveness of bariatric educational programming may be improved if RN
      attitudes and concerns are measured and addressed.

PMID- 16883671
TI  - A continuing education program for hospital and public health nurses to guide
      families of very low birth-weight infants in caregiving.
AB  - Nurses have a critical role in family development of competencies for giving care
      to very low birth-weight infants, However, current information-based methods of
      preparation may be inadequate for competency development. This article describes
      a continuing education program designed to strengthen nurses' support of families
      in developing caregiving competencies through processes of guided participation.
      Program effectiveness was explored with: (1) a survey of participant and non
      participant nurse satisfaction with family work and with organizational resources
      and practices; (2) a description of relationship and caregiving competencies for
      mothers who had and had not received guided participation; and (3) a review of
      mothers' reports of their experience either with or without guided participation.
      Organizational arrangements and mechanisms for establishing guided participation
      practice within an agency, including ongoing reflective supervision sessions,
      peer collaboration, and documentation of competency development, are discussed.

PMID- 16883672
TI  - Becoming a registered nurse: the nurse extern experience.
AB  - Little is known about the perceptions of nursing students externing in newly
      developed hospital-based programs that focus on socialization and transition to
      the registered nurse (RN) role rather than on institutional recruitment and
      retention goals. This qualitative study explored student nurse externs'
      expectations, experiences, and benefits of participation in a student-focused
      externship program. Externs wanted to gain experience with skills and learn what
      it was like to be an RN. Goals were met or exceeded by becoming comfortable in
      the externship role, growing in skill performance and confidence, and becoming
      members of the healthcare team. The experience fostered growth from the novice to
      advanced beginner level of nursing practice. Externs saw the program
      participation as a valuable way to gain experience and learn what it was like to
      be an RN.

PMID- 16883673
TI  - Immunoblot analysis and comparative IgE responses of atopic patients to extracts
      of the domestic mite Blomia tropicalis.
AB  - BACKGROUND: The domestic mite Blomia tropicalis is found in subtropical and
      tropical environments, and its clinical importance as a sensitizing agent in
      allergic disease is widely accepted. OBJECTIVE: To investigate the IgE reactivity
      to allergens present in extracts of the domestic mite B. tropicalis, and compare
      the IgE responses to these allergens by asthmatics, patients with atopic
      dermatitis and allergic rhinitis, as well as nonatopic controls. METHODS:
      Extracts from B. tropicalis were used for skin tests. The B. tropicalis specific
      IgE in the serum were measured using the FAST Plus Test and immunoblot analysis.
      RESULTS: A total of 199 volunteers participated in the study. The data show that
      18 out of 29 polypeptide bands present in extracts of this mite species were
      recognized by the allergic and control sera. Of these allergens, four showed a
      high IgE binding frequency and had relative molecular weights of 104, 80, 68 and
      14 kDa. The 14 kDa allergen demonstrated the highest IgE binding frequency.
      CONCLUSION: Sera from atopic patients reacted to more allergens than sera from
      patients controls. Extracts from pure bodies of B. tropicalis contain one
      immunodominant and three important allergens. A common characteristic between all
      of the sera tested was the high degree of serum IgE reactivity observed to the 14
      kDa allergen.

PMID- 16883675
TI  - Supraphysiological cyclic dosing of sustained release T3 in order to reset low
      basal body temperature.
AB  - The use of sustained release tri-iodothyronine (SR-T3) in clinical practice, has
      gained popularity in the complementary and alternative medical community in the
      treatment of chronic fatigue with a protocol (WT3) pioneered by Dr. Denis Wilson.
      The WT3 protocol involves the use of SR-T3 taken orally by the patient every 12
      hours according to a cyclic dose schedule determined by patient response. The
      patient is then weaned once a body temperature of 98.6 degrees F has been
      maintained for 3 consecutive weeks. The symptoms associated with this protocol
      have been given the name Wilson's Temperature Syndrome (WTS). There have been
      clinical studies using T3 in patients who are euthyroid based on normal TSH
      values. However, this treatment has created a controversy in the conventional
      medical community, especially with the American Thyroid Association, because it
      is not based on a measured deficiency of thyroid hormone. However, just as
      estrogen and progesterone are prescribed to regulate menstrual cycles in patients
      who have normal serum hormone levels, the WT3 therapy can be used to regulate
      metabolism despite normal serum thyroid hormone levels. SR-T3 prescription is
      based exclusively on low body temperature and presentation of symptoms. Decreased
      T3 function exerts widespread effects throughout the body. It can decrease
      serotonin and growth hormone levels and increase the number of adrenal hormone
      receptor sites. These effects may explain some of the symptoms observed in WTS.
      The dysregulation of neuroendocrine function may begin to explain such symptoms
      as alpha intrusion into slow wave sleep, decrease in blood flow to the brain,
      alterations in carbohydrate metabolism, fatigue, myalgia and arthralgia,
      depression and cognitive dysfunction. Despite all thermoregulatory control
      mechanisms of the body and the complex metabolic processes involved, WT3 therapy
      seems a valuable tool to re-establish normal body functions. We report the
      results of 11 patients who underwent the WT3 protocol for the treatment of CFS.
      All the patients improved in the five symptoms measured. All patients increased
      their basal temperature. The recovery time varied from 3 weeks to 12 months.

PMID- 16883674
TI  - Identification and management of Abdominal Compartment Syndrome in the Pediatric
      Intensive Care Unit.
AB  - OBJECTIVE: Asses if Abdominal Compartment Syndrome (ACS) increases the morbidity
      and mortality of the Pediatric Intensive Care Unit patients and if early
      recognition and intervention with decompressive therapy will alter outcome and
      decrease mortality. SETTING: Pediatric Intensive Care Unit of the University
      Pediatric Hospital-UPR. PATIENTS: All patients admitted to the PICU from July 1,
      1999 to June 30, 2002 were enrolled in the study. Those having a distended and/or
      tense abdomen on physical examination were identified at risk for intra-abdominal
      hypertension (IAH). IAH was diagnosed if the intra-abdominal pressure (IAP) was
      above 10 mmHg and with ACS if the IAH was accompanied by: hemodynamic
      instability, oliguria or anuria, metabolic acidosis and respiratory
      deterioration. MEASUREMENTS AND MAIN RESULTS: 1052 patients were admitted to
      PICU. Ten patients with evidence of ACS were identified with an incidence of
      0.9%. Ages ranged from 6 weeks to 12.3 years. Peak intravesical pressure
      measurements ranged from 17 to 39 mmHg. Inspiratory pressure was raised from a
      mean of 21.2 to 32.0 cmH2O. The PCO2 increased from a mean of 35.1 to 63 torr and
      the pH decreased from a mean of 7.40 to 7.12. Overall mortality was 40% for this
      patient population. CONCLUSIONS: The outcome of pediatric critical care patients
      depends on multiple variables. Now there is evidence that in a select group of
      patients IAH and ACS play a significant role in their morbidity and mortality.
      This makes it mandatory for clinicians taking care of this population to be
      increasingly aware of this condition.

PMID- 16883676
TI  - Associations between a history of breast feeding, malocclusion and parafunctional
      habits in Puerto Rican children.
AB  - Studies relating breast-feeding, malocclusion and parafunctional habits in young
      children are scarce. PURPOSE: The purpose of this study is to evaluate the
      associations of a history of breast-feeding, incidence of malocclusion and
      parafunctional habits. METHODS: The dental records of a sample of 540 children
      aged 6 to 72 months screened for oral conditions and behavioral risk factors were
      evaluated for variables such as a history of breastfeeding, malocclusion and
      parafunctional habits. Descriptive statistics using the EPI-INFO Program and Chi
      square test at the 0.05 level of probability were performed. RESULTS: The results
      showed that the mean age of the children was 28 months +/- 14. The mothers' mean
      age was 26.4 years +/- 6. The prevalence of breast-feeding was 34% with a mean
      breast-feeding time period of 3 m +/- 3.7. About 95% of the children had a
      history of bottle-feeding and 90% showed some evidence of malocclusion at the
      time of dental examination. The main malocclusion problems were space deficiency
      (closed contacts among incisors) (31%), open bites (6%) and crossbites (5%). A
      habit of thumb sucking was reported in 32% of the cases and pacifier use in 21%.
      there were significant differences for the following variables: mother's age and
      breast-feeding time period; number of children in family and breast-feeding time
      period; breast-feeding history and breast-feeding time with bottle use,
      malocclusion and thumb sucking habit; and gender and thumb-sucking habit.
      CONCLUSION: It is concluded that breast-feeding practices and time period are
      behavioral factors that contribute in the prevention of malocclusion in addition
      to decreasing the practice of parafunctional habits in preschool children.

PMID- 16883677
TI  - [Immunization program against influenza for adults 65 years or older at a
      community pharmacy in Puerto Rico].
AB  - Evaluate the educational needs of adults over 65 years or more with regards to
      the vaccine, vaccination and immunization against the influenza, design
      strategies to assist the educational needs and implant and evaluate an
      immunization program at an independent community pharmacy. A study divided into
      three phases: Phase I--evaluation of the educational needs related to the
      vaccine, vaccination and immunization. Phase II--designing of strategies to
      assist the needs. Phase III--a random longitudinal controlled study to evaluate
      an immunization program against the influenza implanted at an independent
      community pharmacy. One hundred (100) patients participated, randomly assigned to
      a controlled and experimental group. Three months into the study's Phase III, a
      68% of the experimental group had been vaccinated and showed a tendency to
      improvement in knowledge; in the controlled group, a 32% had been vaccinated and
      did not show a tendency in improvement of knowledge. A year into the study's
      Phase III, a 76% of the experimental group had been vaccinated and 24% of the
      controlled group was vaccinated. The satisfaction average of the experimental
      group towards the pharmacist was 3.94 +/- 0.18 and, in the controlled group was
      3.98 +/- 0.20, whiting a scale of 0-04. People who participated in an educational
      activity offered by a pharmacist showed: more knowledge, remembered what they
      learned and an increase in influenza vaccination.

PMID- 16883678
TI  - Neuroprotection of adult human neurons against ischemia by hypothermia and
      alkalinization.
AB  - Ischemia of intact dorsal root ganglia (DRG) in situ leads to massive neuron
      death due to ischemia-triggered secondary events, such as massive release of
      excitatory amino acids from the neurons, their excessive accumulation and
      activation of neuron NMDA and other receptors, acidification, and loss of calcium
      homeostasis. The present experiments tested whether hypothermia and
      alkalinization, separately or combined, provide neuroprotection against 1-4 hours
      of ischemia to the neurons within intact DRG acutely removed from organ donors.
      DRG under hypothermic (20-15 degrees C) or alkaline (pH 8.0-9.3) conditions
      yielded more viable neurons than DRG maintained under physiological conditions
      (37 degrees C/pH 7.4), 4.1-fold vs. 7.8-fold respectively, but, hypothermia and
      alkalinization combined (20 degrees C/pH 9.3) increased the yield of viable
      neurons 26-fold compared to DRG maintained under physiological conditions. These
      results show that combined hypothermia and alkalinization provide adult human DRG
      neurons significant neuroprotection against ischemia, and ischemia-induced causes
      of neuron death.

PMID- 16883679
TI  - Are there causal relationships between the development of the inflammatory
      diseases amyotrophic lateral sclerosis and asthma?
AB  - Amyotrophic lateral sclerosis (ALS) and asthma are inflammatory diseases. ALS is
      a fatal progressive, neurodegenerative disease with inflammation around the upper
      and lower motor neurons leading to their degeneration, muscle atrophy, paralysis,
      and death. Asthma is a chronic inflammatory disease with reversible airway
      obstruction and nonspecific airway hyper-reactivity. The local release of sensory
      neuropeptides from capsaicin-sensitive primary afferents causes motor neuron
      pathophysiology and airway inflammation and hyper-reactivity. While there is no
      cure for ALS, asthma is managed according to its symptoms and severity, to
      decrease the symptoms, improve pulmonary function, and reduce morbidity. To
      determine whether understanding asthma may provide insights into how to
      clinically deal with ALS, the authors examined the etiologies of ALS and asthma,
      and the factors that exacerbate the symptoms. Although no direct correlations
      were found, the similar multifactorial triggers, and the critical roles of
      neuronal inflammation, suggest that one or more exists.

PMID- 16883680
TI  - Medical examiner samples: a source for dengue surveillance.
AB  - Post-mortem medical examiner samples may be useful for sentinel surveillance of
      disorders usually detected by antibody determinations on specimens from ill
      patients or from surveys. We found anti-dengue IgM positivity in 3% (23/780) and
      anti-dengue IgG positivity in 77% (597/777) of sera obtained at the Puerto Rico
      medical examiner (Institute of Forensic Sciences) in December 2000, April 2001,
      and October 2001. This approach may be a useful alternative for estimating the
      population prevalence of serologic markers for dengue and other infectious
      diseases.

PMID- 16883681
TI  - Tumor growth parameters of in-vivo human breast carcinoma: a proposed
      mathematical model for tumor growth kinetics.
AB  - Many mathematical models have been proposed to study tumor growth parameters in
      vivo. Nevertheless most of the medical models have given variable results even
      when experimental conditions are exactly the same. There are multiple factors
      that are capable of affecting tumor growth that should be taken into account when
      proposing a mathematical model for tumor growth in vivo. We discuss here own
      proposed model for tumor growth kinetics utilizing a modified Gompertz function
      that better responds to the growth characteristic of in "vivo" tumors.

PMID- 16883683
TI  - Free jejunal intrathoracic graft after esophageal replacement failure.
AB  - We present the case of a 24 year old man who suffered from severe chronic
      esophagitis and an esophageal stricture. He was managed by gastric pull-up but
      complicated by leakage of the anastomosis. Subsequent sophageasurgical treatment
      with free jejunal graft was performed and the rationale for the technique
      selected is discussed.

PMID- 16883682
TI  - Effect of hydrodynamic environment on tablet dissolution using flow-through
      dissolution apparatus.
AB  - The main objective of this research is to investigate the principles underlying
      the dissolution process, study the phenomena of drug release in laminar flow, and
      better understand the effect of hydrodynamic condition on drug dissolution, in
      order to predict drug dissolution from a solid dosage form. Two drug models were
      selected, theophylline (Class I) and naproxen (Class II), and were formulated
      into conventional tablets containing 105 mg theophylline or 300 mg naproxen using
      wet granulation method. Additionally theophylline (105 mg) and naproxen (300 mg)
      matrices containing 30% hydroxypropylmethylcellulose (HPMC) polymer were prepared
      by direct compression and tested for dissolution using both USP II and IV
      dissolution apparatus. Tablets were tested for dissolution (USP IV) using
      different cell diameter, flow rate, and different position of the tablet inside
      the cell. In general, the drug dissolution at a given time is a direct function
      of the flow rate, increasing the flow rate increases drug release. The use of a
      small cell resulted in faster drug dissolution and higher Reynold's Number than
      using a large cell. Tablet position in the cell, also has an effect on drug
      dissolution, inserting the tablet in a horizontal position inside the cell gave
      faster dissolution than a vertical position. The hydrodynamic conditions did not
      affect the drug dissolution from HPMC controlled release tablets indicating that
      the drug dissolution is controlled by the matrix. An equation to predict drug
      dissolution from conventional tablets was established: Sh=-21.36+10.58Re(1/2)
      where R2=0.98. This study demonstrated that hydrodynamic conditions, and type of
      dissolution testing apparatus used have an effect on dissolution rate, mass
      transfer rate, and film thickness underlying dissolution process.

PMID- 16883684
TI  - [Usability of PCR-based techniques for diagnosis of parasitic infections in
      ruminants].
AB  - Sensitivity and specificity are the two most important criteria that define the
      quality of a diagnostic technique. DNA probes and PCR-based techniques may
      simplify the diagnosis of parasitic infections. PCR is a powerful diagnostics
      tool. The method enables detection of even a very small amount of DNA. An extreme
      sensitivity of the PCR, being a major advantage of the method is also a cause of
      potentially false positive results. To achieve reliable diagnostic results
      several modifications have been introduced to the classic PCR procedure. PCR and
      PCR-based techniques are currently increasingly used for detection of parasitic
      infections, to differentiate closely related species which are difficult to be
      recognised with traditional methods, for estimation of parasite burdens, and for
      the detection of drug resistant strains.

PMID- 16883685
TI  - [Toxicoses of ticks (Acari: Ixodida)].
AB  - Toxins have been shown to present in the salivary glands, whole body extracts,
      and eggs of ticks. They cause histological lesions in the skin, and in various
      organs of tick hosts. Among toxicoses, tick paralysis is of the greatest medical
      and veterinary importance. Toxins are secreted by cells "b" of acinus II in
      salivary glands during tick feeding.

PMID- 16883686
TI  - [Immune response and diagnostic aspects during Toxoplasma gondii infection].
AB  - Toxoplasmosis is a common and generally benign disease in immunocompetent persons
      caused by Toxoplasma gondii, which is an intestinal coccidian parasite of
      felines. Diagnosis of toxoplasmosis is mainly based on the results of serological
      tests detecting anti-T. gondii specific antibodies, but T lymphocytes and
      cytokines they produce play a crucial role in determining the outcome of
      parasitic infection in terms of both protective immunity and immunopathology.

PMID- 16883687
TI  - [Antigens of Toxoplasma gondii].
AB  - The paper presents antigenic structure of T. gondii tachyzoites and bradyzoites
      in respect of potential use of some chosen antigens for diagnostic and
      immunoprophylactic purposes.

PMID- 16883688
TI  - [Parasitoses in immune deficiences].
AB  - The congenital or acquired cause the state of immune deficiency. To acquired
      factors belong immunosuppressive therapy after grafting and in systemic diseases
      as infections with HIV. There is a number of parasitic organisms, mainly
      protozoa, which preferentially settle in immunocompromised persons. The
      opportunistic parasites are present in the nearest environment. Some of them were
      newly recognized as human invaders. The state of immune deficiency may reactivate
      latent infections, that occurs with Toxoplasma gondii infection. Some parasitic
      infections which are benign and self- resolving, when affecting immunocompetent
      hosts, become fulminant or disseminated and very often life - threatening in
      immunosuppressed individuals.

PMID- 16883689
TI  - [Strongyloidosis. Part VII. Epidemiology and prevention (2)].
AB  - The formation of Strongyloides stercoralis infections in the tropical countries
      and in the temperate climatic zone, with special attention to the factors and the
      high risk groups, were described. The concurrent infections, prevention and
      control of strongyloidosis was also presented.

PMID- 16883690
TI  - [Travassosius rufus (Trichostrongylidae)--new for Poland nematode of beavers and
      comments about helminthfauna of these animals].
AB  - Two females of beaver from north-east Poland were necropsied. Moreover, 15
      samples of feaces were examinated. Both necropsied beavers were infected with 46
      and 362 specimens of trematode Stichorchis subtriquetrus (RUDOLPHI 1814). In
      stomach of one beaver were found 2800 specimens of nematode Travassosius rufus
      Khalil, 1922. It was the first registration of this species in Poland.
      Coproscopical examination showed eggs of S. subtriquetrus in all 15 fecal samples
      and eggs T. rufus in 5 samples.

PMID- 16883691
TI  - Disturbances of mouse pregnancy after injection of Ascaris homogenate during
      early organogenesis.
AB  - Administration of the Ascaris tegumental homogenate (0.6-1.2 g of Ascaris
      proteins/kg/day) at a early stage of organogenesis (5-9 days of pregnancy) had a
      harmful effect upon the developing mouse fetuses. It has been found that
      injection of the homogenate did not delay or prevent implantation, but causes a
      high rate of intrauterine deaths. The Ascaris homogenate significantly decreased
      the number of live fetuses per litter, increased the frequency of litter
      resorption, produced a delay in bone formation and induced pathological changes
      of fetal organs and tissues. The congenital malformations were noted in fetuses
      after injection of higher doses of Ascaris homogenate (exencephaly,
      craniomeningocele and internal hydrocephalus). No malformations were noted in
      control groups and after injection of minimum dose of the homogenate. The
      symptoms that occurred after administration of the tegumental homogenate to
      pregnant mice included: decreased body weight gain (p<0.001) as compared to
      controls, vaginal hemorrhage, intrauterine resorption of litter and mortality.
      These signs suggest that the Ascaris homogenate causes maternal toxicity.

PMID- 16883692
TI  - New larval mites (Acari: Prostigmata: Erythraeidae, Microtrombidiidae,
      Trombidiidae) from Turkey, Peru and Poland.
AB  - The following species are described as new: Erythraeus (E.) sifi n. sp., E. (Z.)
      didonae n. sp., Bursaustium gaspari n. sp. from Turkey, Charletonia alvedae n.
      sp., Balaustium medardii n. sp., Yucothrombium ilzae n. sp. from Peru and
      Allothrombium wolmari n. sp. from Poland. Three new genera are created:
      Rudaemannia n. gen., Bursaustium n. gen. and Yucothrombium n. gen. Erythraeus
      kresnensis, Charletonia cardinalis, Podothrombium proti, Allothrombium
      fuliginosum and A. triticium are new to the fauna of Turkey; Hauptmannia
      wratislaviensis is new to the fauna of Scotland. New localities in Poland are
      given for H. stanislavae and H. silesiacus and in Turkey for Rudaemannia
      rudeansis. Charletonia tamarae is synonymous to C. bucephalia; Hauptmannia
      victicola is synonymons to R. rudaensis.

PMID- 16883693
TI  - The occurrence of the nematodes anisakis simplex pathogenic to man in pike-perch
      from the Vistula Lagoon, Poland.
AB  - Of the 400 pike-perches examined, 12% were infected with L3 Anisakis simplex. The
      infected fish were over 45 cm long. The hypothesis submitted was that the pike
      perches may constitute the source of infection in accidental hosts, i.e. in man.

PMID- 16883694
TI  - Variability of the reproductive system of Piscicola fasciata (Kollar, 1842
      (Hirudinea, Piscicolidae).
AB  - The studies on the reproductive system of P. fasciata were based on 43 specimens.
      Two main types of the reproductive system can be distinguished in the studied
      population. Two types of reproductive system were the most frequent (20.93%
      each): with symmetrical ejaculatory ducts without a loop and symmetrical seminal
      vesicles reaching the end of the first pair of testes, situated next to the
      testes (adult individuals) (fig. 23) and with symmetrical ejaculatory ducts
      without a loop (fig. 21) and symmetrical poorly developed seminal vesicles
      situated asymmetrically anterior to the first pair of testes (juvenile
      individuals). The structure of the reproductive system corresponding with the
      description of the type specimen (BRUMPT, 1900) was not observed in the studied
      population.

PMID- 16883696
TI  - [Contracaecum rudolphii Hartwich, 1964 (Nematoda: Anisakidae) in the great
      cormorants in Poland].
AB  - It is the first report on Nematoda Contracaecum rudolphii in the great cormorants
      Phalacrocorax carbo (Linneus, 1758) in Poland.

PMID- 16883695
TI  - [Co-occurrence of parasites sensu lato in alimentary tract of patients
      hospitalised in lower Silesia].
AB  - Up to now, the co-occurrence of parasites sensu stricto and fungi were confirmed
      mostly in the oral cavity. The aim of the present parallel parasitological and
      mycological investigations was to determine co-occurrence of protozoa, helminths
      and fungi (parasites sensu lato) both in smears from cavity and in stool samples
      of 93 patients undergoing the non-parasitological treatment in two hospitals of
      Lower Silesia (Poland). Among the examined patients parasites sensu lato (13
      species) were found in 62 cases (63%). Trofozoites of Trichomonas tenax and/or
      Entamoeba gingivalis as well as fungi (Candida albicans, C. krusei, C. tropicalis
      and C. pseudotropicalis) occurred in 10% of the examined patients. Almost all
      infected cases (90%) were joined with infection of common invasion of protozoa
      and fungi. In stool common invasion of parasites sensu lato (Giardia
      intestinalis, Entamoeba coli, Ascaris lumbricoides, Taenia sp., Enterobius
      vermicularis as well as Candida albicans, C. krusei, C. pseudotropicalis, C.
      guilliermondii and Rhodotorula sp.) were found in 12% of the patiens. The co
      occurrence of parasites and fungi was stated in the half of invasions. C.
      albicans was the most often co-occurring species in alimentary tract.

PMID- 16883698
TI  - [The data from the first investigations of a new antioxidants family-
      peroxidoxins--in parasites].
AB  - The properties and mechanism of action of a new family of antioxidants
      peroxidoxins-have been described. The properties of parasitic peroxidoxins in
      some helminths and protozoans discovered as a result of genom sequencing and
      expressed sequence tag (EST) project have been presented. The data described
      untill now from a number of studies with parasites indicate that the family of
      peroxidoxins, very important for the host-parasite interactions may be in future
      a potential candidate vaccine molecules in some systems.

PMID- 16883699
TI  - [The immune response of various species to Fasciola hepatica infection].
AB  - The trematode F. hepatica is an internal parasite of many species of animals
      including men. In ruminants, fasciolosis is an economically important disease
      often resulting in a chronic and sub-clinical infection. The mechanisms of immune
      responses of final hosts to this infection are still poorly understood.
      Experimental and clinical studies reported so far suggest that both humoral and
      cellular effectors of the immune response are important to control the duration
      of F. hepatica infection. However, there are considerable variation both inter
      species and between various strains of the same species in regulation of the
      response as well as abilities to develop resistance to subsequent infections.

PMID- 16883700
TI  - [Toxoplasma gondii--intracellular parasite].
AB  - The article presents selected data concerning invasion and intracellular life of
      obligate intracellular parasite Toxoplasma gondii in susceptible hosts.

PMID- 16883701
TI  - [Impacts of climate change on infectious diseases].
AB  - Climate warming may have significant impacts on human health, including changes
      in the distribution and seasonality of vector-borne diseases. We discuss the
      consequences of climate change on infectious diseases. Effects of transmission of
      the imported tropical diseases in Europe are discussed.

PMID- 16883702
TI  - [Studies upon behaviour of snails in anthropogenically changed water environment.
      1. Locomotor activity of Lymnaea stagnalis (L.), with regard to subpopulations
      infected with developmental stages of digeneans].
AB  - The aim of the paper was to analyse the locomotor activity of snails, Lymnaea
      stagnalis, with regard to physico-chemical properties of water in an inhabited
      reservoir and parasitic infection. The material was collected in selected
      anthropogenic water environments situated in the Upper Silesian Industrial Region
      (sinkhole ponds, sand- and clay-excavations). The locomotor activity of each
      snail was analysed in laboratory conditions by designation of number of
      penetrated segments, marked in tanks filled with water originating from a given
      reservoir, during 15', with intervals of 1'. It was observed the significant
      relationship between locomotor activity of examined snails and the water
      carbonaceous hardness (r = -0,812, at range of the independent variable 173.0
      863.5 mg CaCO3/dm3). Correlation coefficients with other physico-chemical
      parameters of water were close to zero. Locomotion of snails infected with
      developmental stages of digenetic trematodes was significantly lower comparing to
      non-infected individuals. Locomotor activity of these former ones was dependend
      more on degree of the digestive gland damage by the parasite than on the
      infection agent.

PMID- 16883703
TI  - Developmental abnormalities in chicken embryos after injection proteolysis
      inhibitors from Ascaris suum.
AB  - It has been found that trypsin and alpha-chymotrypsin inhibitors isolated from
      Ascaris suum act embryotoxically and teratogenically on White Leghorn chicken
      embryos. Mortality rate for the chicken embryos on day 15 of incubation was 45.0
      +/- 3.5% after injection of trypsin inhibitor and 44.0 +/- 3.5% after
      adminstration alpha-chymotrypsin inhibitor. Gross examination of surviving
      embryos and their dissection revealed pathological changes (abdominal dropsy,
      umbilical hernia, subcutaneous oedema, hemoperitoneum, hemopericardium), symptoms
      indicating retardation in growth (lack of down, retarded ossification of long
      bones, decreased mean body weight) as well as malformations (schistocelia,
      micrognathia, cyclopia, crossed beak, cranial deformities) after injection of
      inhibitors from Ascaris. The highest incidence of embryos with pathological
      changes and malformations was found after administration of alpha-chymotrypsin
      inhibitor. The most commonly occurring abnormality was schistocelia (21.4 +/-
      3.88%). Growth malformations were not found in the control groups. The trypsin
      and alpha-chymotrypsin inhibitors present in Ascaris homogenate have a
      significant disturbing effect on the development of the chicken embryo.

PMID- 16883704
TI  - Raccoon dog (Nyctereutes procyonoides)--the new host of Echinococcus
      multilocularis in Poland.
AB  - The alimentary canals of 9 species of domesticated or wild animals were examined
      for the presence of E. multilocularis. The tapeworm was found in 9 red foxes
      (Vulpes vulpes) out of 155 examined (5.8%) and in 2 raccoon dogs (Nyctereutes
      procyonoides) of 25 examined (8.0%). Our studies proved that in Poland the
      raccoon dog can also be infected with E. multilocularis.

PMID- 16883705
TI  - Deformations of the attachment organ in Diplozoidae (Palombi, 1949) (Monogenea).
AB  - This work consisted in studying the frequency of deformations of the attachment
      organ in specimens representing the family Diplozoidae, occurring in roach,
      common bream, and white bream from five different water bodies. These water
      bodies differed in morphometric parameters, levels of eutrophication, and
      character of their pollution. The presence of three types of deformation was
      stated. The most common were deformations of type II (morphological changes of
      clamps, such as sclerite deformation, incomplete sclerite separation or sclerites
      missing altogether in a clamp), while less frequent were those of types I
      (changes in the size of clamps not associated with the structural changes) and
      III (missing clamps in a set). Most frequently anomalies of the attachment organ
      were stated in polluted Lyna River, polluted Wulpinskie Lake, and in dystrophic
      Warniak Lake. Less frequent were anomalies in less eutrophied lakes Dgal Wielki
      and Ukiel. Also the prevalence values of those parasites were the highest in the
      polluted water bodies. The present study supports believes of other authors, that
      both infection parameters of Diplozoidae affecting fishes and deformations of
      monogeneans' attachment apparatus can be treated as indicators of environmental
      pollution.

PMID- 16883706
TI  - [Influence of the selection of maternal Hymenolepis diminuta WMS il1 on the
      variability of descended tapeworms].
AB  - A continuation of a single-individual culture of Hymenolepis diminuta WMS ill
      from generations 37 to 66 revealed a very high infective ability of cysticercoids
      which is reflected in the percentage of tapeworms detected in relation to the
      number of cysticercoids given to rats (94.4%). The tapeworms investigated
      revealed a significant increase in the abundance of type 0p3a proglottids (those
      with no testes on the poral side and 3 on the aporal) in tapeworms of successive
      generation groups. Each group of tapeworms analysed statistically belonged to
      three successive generations and numbered 31-34 individuals. The mean abundances
      of 0p3a type proglottids in tapeworms of the first groups studied in experiment,
      including generations 37-39 and 40-42 were 9.2% and 9.5%, respectively. The last
      studied groups, including generations 61-63 and 64-66 had higher mean numbers of
      type 0p3a proglottids, at 11.1% and 11.5%, respectively. The quantitative figures
      of 1p3a type proglottids amounted to 1.6% and 1.3% in first generation groups and
      in the last two groups 0.8% and 1.0%, respectively. The probable cause of this
      significant (P < 0.01) relative increase in the numbers of 0p3a type proglottids
      and decrease (P < 0.01) in the numbers of 1p3a type proglottids was the
      deliberate selection of maternal tapeworms characterized by numbers of 0p3a type
      proglottids greater and 1p3a type proglottids smaller than the average for their
      generation.

PMID- 16883707
TI  - [A rapid method for preparing semipermanent glycerol-jelly parasite mounts].
AB  - A rapid method for preparing semipermanent glycerol-jelly mounts of monogeneans,
      digeneans, nematodes, acanthocephalans, and crustaceans is presented.

PMID- 16883708
TI  - [1st Workshop on Bird Schistosomes and Cercarial Dermatitis].

PMID- 16883709
TI  - [Professor Feliks Piotrowski, Ph.D. (1921-2000) (Obituary notice)].

PMID- 16883710
TI  - [Statement Report of the Polish Parasitology Society from September 1998 till
      September 2001].

PMID- 16883711
TI  - [More about 8th European Multi-colloquium of Parasitologists].

PMID- 16883712
TI  - [Host location by ticks (Acari: Ixodida)].
AB  - Ticks respond to host stimuli, such as higher CO2 concentrations,vibrations,
      odour, touch, radiant heat ad kairomones. The behaviour al reactions to these
      host stimuli vary among tick species. Among these arthropods hunter (actively
      running in the direction of host) or ambusher ticks (passively waiting for host
      on the vegetation) occur. Hallers organ, palpal organ, cheliceral organ and
      receptors on scutum and alloscutum are involved in tick feeding behaviour.

PMID- 16883713
TI  - [Strongyloides stercoralis (Bavay, 1876) Stiles et Hassall, 1902 (Nematoa). Part
      IV. Life cyclec].
AB  - The life cycle of parasitic and free-living generation of Strongyloides
      stercomlis were described. Factors influencing development of parasitic and free
      living generations of S. stercoralis were also described.

PMID- 16883714
TI  - Glossiphoniidae Vaillant, 1850 (Hirudinea) of Poland--systematics and
      perspectives of studies.
AB  - Taxonomic and biological-ecological information as well as literature pertaining
      to the eleven Polish representatives of glossiphoniid leeches are summarized.
      Taxonomic status of many species is unclear, and data on their life histories are
      often fragmentary. The existence of several different conflicting systems of
      glossiphoniid classification indicates that the taxonomical value of characters
      is unclear. The family requires a thorough modern revision. A new generic-level
      classification of the family is needed. Data on behaviour and life cycles of
      mostspecies should be supplemented; anatomical variation and differences between
      the purported forms of glossiphoniid species should be re-examined. A detailed
      study on the life cycles and variation of the Polish members of the
      Glossiphoniidae would provide new and valuable data and would allow at least for
      proposing a good, modern standard of species description without which a world
      wide revision is hardly possible.

PMID- 16883715
TI  - Histochemical study of the nitric oxide synthase activity in experimental
      trichinellosis.
AB  - Nitric oxide plays a critical role in a variety of biological activities. It has
      been nicknamed a "killer" and "mediator" due to its toxic and signalling
      properties. Apart from its regular physiological function, nitric oxide
      indirectly participates in infectious diseases. Our report seems to be the first
      presentation of the nitric oxide synthase participation in the host biochemical
      defence mechanisms and in morphological transformation of muscle cells in
      trichinellosis.

PMID- 16883716
TI  - [Epidemiological studies on giardiosis in inhabitants of Szczecin].
AB  - The aim of the studies was to establish the prevalence of Giardia intestinalis in
      Szczecin population. The studies were carried out in 1991 - 1996. In this period
      46,584 persons--22,371 adults and 24,213 children were examined. Faecal samples
      were examined with two methods--coprological and immunoenzymatic (ELISA) test. A
      total of 356 persons (0.78%) were found to be infected with G. intestinalis. No
      statistically significant differences between the infection rate of adults and
      children were observed. The adults were infected in 0.73% and the children in
      0.80%. The analysis of the annual dynamics of G. intestinalis infection shows
      twice as large infection rate in September - October (1.18%) as in the remaining
      months (0.66%).

PMID- 16883717
TI  - [Intestinal parasites in inhabitants of Wroclaw and Walbrzych].
AB  - In the period 1990-1997 several thousand patients from Wroclaw and Walbrzych
      hospitals as well as inhabitants of Wroclaw city were examined for intestinal
      parasites. The presence of parasites was noted in 12.3% of 2173 patients from the
      District Hospital of Infectious Diseases in Wroclaw, 3.2% of 599 from Walbrzych
      Hospital and 39.3% (mostly Enterobius vermicularis) of 746 ambulatory examined
      persons in the Private Analytical Laboratory in Wroclaw. Among the intestinal
      protozoa the most frequent was Giardia intestinalis (from 5.7 to 18.1%) and
      Entamoeba coli (0.5-0.6%); the remaining amoebas (E. histolytica, E. hartmanni,
      E. polecki and Endolimax nana) as well as Chilomonas mesnili was present only in
      single cases. Enterobiosis was observed in nearly half of the total number of
      examined children (1808); the most rarely found helminths were Opisorchis
      felineus (! Adult patient), Strongyloides stercoralis (2) and Trichuris trichiura
      (8); Taenia saginata was found in 56 patients, which constituted 1.6% of the
      total number of examined cases and Ascaris lumbricoides in 40 (1.2%).

PMID- 16883718
TI  - Extracerebral infections of Acanthamoeba spp. in mice. pathomorphological changes
      in tissues of infected animals.
AB  - A variety of Acanthamoeba spp. pathogenic strains were isolated from water pools
      in the area of Poznan. In many cases amoebae invaded lungs, kidney heart, liver
      and diaphragm causing significant changes in these Organs. The presence of amoeba
      outside of CNS was found mainly in the early periods of infection. Amoeba
      isolated from different organs of dead animals did not exhibit any specificity in
      relation to the organs in following infections. Infection with both low-and high
      virulent strains resulted in pathomorphological changes of similar character.
      However, changes induced by low-virulent parasites developed later and were less
      extensive.

PMID- 16883719
TI  - [Biological infection of soil on the flooded areas of Wroclaw City].
AB  - The distribution of geohelminth eggs on the appartment backyards of Wroclaw city
      after flood disaster was studied. Out of 100 soil samples examined 17% were
      positive. Toxocara spp.eggs were present in 6% samples examined, Ascaris spp. in
      2% and other eggs (Capilaria sp. and Trichuris vulpis) in 9% samples examined.
      Soil contamination of Wroclaw area was much less than in other cities of Poland
      and Europe. The prevalence of geohelminth eggs on flooded areas was very similar
      to that on the not-flooded areas although the number of eggs recovered was twice
      as high on flooded areas.

PMID- 16883720
TI  - Coverage crisis continues; local advocates take action.

PMID- 16883721
TI  - Community benefit guidelines born of shared experience.

PMID- 16883722
TI  - Globalization and Christian love.
AB  - Globalization is having a very negative impact on the world's poorest people.
      Decisions made in the First World-decisions often based on a profit-oriented
      ethic-are degrading the quality of life of people in the Third World and taking
      away their voice. The church is called to act in solidarity to respond to people
      in need worldwide. It must take a radical stance to promote love, justice,
      development, and peace. Acting in solidarity with others expresses a commitment
      to the common good and recognizes that all people are interconnected-that "our"
      well-being depends on the well-being of others. It acknowledges that people exist
      within a community. The concept of solidarity-with its emphasis on relationships
      among people-runs counter to many of the structures that drive globalization.
      People of the church must undertake a personal assessment, examining their
      thoughts and feelings about acting in solidarity with people in need. Through
      change and personal action, these individuals can promote justice around the
      world.

PMID- 16883723
TI  - Embracing global solidarity.
AB  - For more than 60 years, Catholic Relief Services (CRS) has provided emergency
      relief overseas. But the guiding principles underlying the organization's work
      have evolved over time-particularly over the last decade-as staff members have
      adopted a new view of their role in supporting people in need worldwide. In CRS'
      early years, its focus was on corporal works of mercy: providing food, drink,
      clothing, and other material goods. Although the organization's breadth of
      services and geographic presence expanded throughout the latter part of the 20th
      century, it wasn't until the mid-1990s that the agency questioned its
      foundational principles and made an organization-wide move toward change. The
      impetus for change was the 1994 Rwandan genocide crisis. CRS staff members were
      deeply affected: not only were their aid programs destroyed; they also lost
      friends, colleagues, and family members. CRS staff realized that unless they
      addressed the justice issues underlying their beneficiaries' concerns, their aid
      would have minimal impact. Changing the way the organization approaches relief
      has been an extensive process. Staff members developed a strategic plan, held
      retreats and workshops to define the concept of justice, educated colleagues
      worldwide on the new approach, facilitated "Justice Reflections" to explore the
      basics of Catholic social teaching, and developed guiding principles and a
      vision. Despite challenges, CRS is successfully transforming itself into an
      agency that not only provides physical relief but also strives to help build a
      culture of justice, peace, and reconciliation.

PMID- 16883724
TI  - An uncommon international venture.
AB  - A collaboration involving Franciscan religious communities in the United States
      and Cameroon, Africa, demonstrates that a spirit of mutuality and cross-cultural
      understanding can develop among partners in aid projects. Three United States
      based communities of Franciscan women religious developed the "Common Venture"
      project as a way to celebrate their common history while undertaking systemic
      change. Wanting to have an international impact, they developed a relationship
      almost a decade ago with the Tertiary Sisters of St. Francis in Cameroon. The
      result was a collaborative project through which the sisters sought to discover
      the deeper meaning of their vocation and their community membership; seek
      resources to further the Cameroon ministry; and identify organizations to support
      their work. Much has been accomplished in the ensuing nine years. This Common
      Venture effort has inspired a "minor revolution" in aid efforts in Cameroon and
      beyond. It has brought education and training programs, improved health care
      access, supplies and medicine, medical volunteers, and other improvements to this
      African community. And the U.S. partners also have benefited, gaining great
      satisfaction from helping people in need develop long-term solutions to problems.

PMID- 16883725
TI  - Carrying our founders' mission overseas.
AB  - Catholic' health care providers have a calling to care for people in need, and
      that mission does not stop at geographical boundaries. In fact, U.S. health
      facilities in many cases were founded by overseas religious communities with a
      mission. Providing aid internationally enables U.S. sites to carry on that
      legacy. Although Americans traveling overseas to provide aid usually expect to be
      "teachers", they often find themselves becoming "students" instead. They learn to
      provide care without the advanced technology that is available in developed
      countries. They often experience cultures in which people can only hope for care
      access and in which patients are deeply appreciative of the services they
      receive. This type of education can change U.S. health care providers'
      perspective of their role and of the services they deliver. While gaining this
      wisdom-and imparting their own knowledge-providers also affect the quality of
      life of people in developing countries. In the end, global aid can create a
      better world for everyone, benefiting not only the recipients but also the
      worldwide community. When developing countries become more stable, develop
      stronger infrastructures, and have healthier citizens, other countries benefit
      from this progress.

PMID- 16883726
TI  - Health care and the global community.
AB  - Catholic health systems and facilities, to fulfill their commitment to the
      healing ministry of Jesus Christ, are called to serve society's most poor and
      vulnerable people. This calling applies to people in need not only locally but
      also internationally. Individuals and organizations providing aid in foreign
      lands will face many challenges. Yet if they believe that they can use their
      expertise to benefit people in need, they can accomplish their goals. Some
      guiding principles are instructive for those undertaking international outreach
      efforts: Partners must commit themselves to a common mission; the effort must
      focus on empowering aid recipients; participants in the effort-donors and
      recipients alike-can experience transformation; and health and well-being must be
      central to the work. The Catholic Consortium for International Health Services
      (CCIHS) has experience in following these principles to bring about change. The
      consortium can help ministry organizations achieve their international outreach
      goals.

PMID- 16883727
TI  - Building Upendo Village: a global effort.
AB  - What began as a conversation in 2000 between two women religious on how to help
      Kenyans affected by HIV/AIDS has evolved into a far-reaching ministry supported
      by the Wheaton Franciscan sisters. Inspired by the parable of the Good Samaritan,
      Sr. Florence Muia, ASN, a native of Kenya, explored with Sr. Marge Zulaski, OSF,
      a Wheaton Franciscan sister, how to offer assistance and support to Kenyans with
      HIV/AIDS. The two began by establishing a partnership involving the Wheaton, IL,
      congregation; the Assumption Sisters of Nairobi; and community members in Kenya.
      These partners have worked together closely to secure local community members'
      buy-in for a care program, study models for success, build a program
      infrastructure, secure funds, staff up, and interact with government agencies.
      The result? Upendo Village, a program that helps ensure the physical, economic,
      and emotional safety of people suffering from HIV/AIDS. This partnership has
      enabled the Wheaton Franciscans, the Assumption Sisters, and the Kenyan community
      to live out a simple principle: We are called to help each other.

PMID- 16883728
TI  - Making global solidarity local.
AB  - In an effort to strengthen services for local immigrants, Catholic organizations
      throughout Ohio are turning to the newcomers' home countries to learn more about
      their culture and needs. The outreach has helped these ministries to address the
      challenges immigrants face and to provide services in a culturally appropriate
      way. This intensified focus on the newcomers' plight began in earnest in 2001,
      when three northeastern Ohio dioceses created a collaborative to address the
      social, pastoral, and legal needs of their "new neighbors". The dioceses
      established a centrally located site to provide a wide range of services; but,
      early on, the collaborative recognized that access to health care was a
      particular challenge for the immigrants. Wanting to fully understand the
      newcomers' origins before developing health care solutions for them,
      representatives from the collaborative visited countries from which many
      immigrants migrate to Ohio. The trips were instructive: The visitors not only
      learned about the cultural idiosyncrasies of each area they visited; they also
      discovered how church organizations there developed solutions to their own health
      care access problems. The Ohio collaborative has used this wisdom to tailor its
      health care offerings to meet the unique needs of area immigrants. The ongoing
      relationship between Catholic organizations in the United States and those abroad
      continues to yield valuable insights that benefit the immigrant community.

PMID- 16883729
TI  - 2006 CHA Mission leaders Survey 1.

PMID- 16883730
TI  - End-of-life care revisited. Recent debates have raised some important
      foundational questions.

PMID- 16883731
TI  - Thirsting for solidarity.

PMID- 16883733
TI  - [In the dark].

PMID- 16883732
TI  - The role of the diocesan bishop in relation to Catholic health care.

PMID- 16883734
TI  - [Obstetrics and its outcomes--"maternal health" in Germany: supporting pregnant
      women].

PMID- 16883735
TI  - [Comment on the contribution, "Intervention and promotion of ethical competence
      in geriatric nursing. Basic principles of quality assured professional nursing"
      by Ulf Dettman, issue 2/2006].

PMID- 16883736
TI  - [Children as visitors in adult intensive care units--literature review: guided
      interventions support adaptation work].

PMID- 16883737
TI  - [Effectiveness of massage of premature and newborn infants: what gets below the
      skin].

PMID- 16883738
TI  - ["Giraffe OmniBed--a bed for all? Warm heat therapy device has multiple
      applications].

PMID- 16883739
TI  - [Study of virtual self help groups after prenatal loss: not being alone in the
      grief process].

PMID- 16883740
TI  - [Management of premature infants and their parents: "premature infants are
      special patients"].

PMID- 16883741
TI  - [Hygiene series--13: Pregnancy, labor and puerperium: preventing infections].

PMID- 16883742
TI  - [Febrile convulsion as pediatric emergency: panic is the wrong way].

PMID- 16883743
TI  - [Palliative management in pediatrics: responding to needs at the child
      appropriate level].

PMID- 16883744
TI  - [Oral mucositis in patients with tumor therapy--2: Experiencing and understanding
      oral hygiene].

PMID- 16883745
TI  - [Health promotion in nursing between claims and reality--1: From patient nurse to
      public health nurse].

PMID- 16883746
TI  - [Work-life balance in routine nursing practice: living in harmony].

PMID- 16883747
TI  - [Effects of strike on surgical management at the Cologne Uniclinic: breaking away
      from old structures, following new paths].

PMID- 16883748
TI  - [Family members in intensive care units--possibilities and boundaries of
      integration of family networks into the nursing care process].
AB  - Patients' family members are often regarded rather as a burden in intensive care,
      but they need personalised contact, information and support as much as the
      patients themselves. The concept of "family nursing" tries to integrate positive
      social mechanisms of support family members try to provide. For a short term
      nursing staff has to do some extra work, but seen from a wider angle this can
      become an important contribution to successful care. This approach can only be
      realised by an interdisciplinary collaboration of the professional team.

PMID- 16883749
TI  - Optic neuritis dueto multiple sclerosis.

PMID- 16883750
TI  - Mediastinal lymphangiohemangioma associated with superior vena cava ectasia.

PMID- 16883751
TI  - Angiosarcoma of right cardiac atrium.

PMID- 16883752
TI  - Endolymphatic sac tumor of temporal bone.

PMID- 16883754
TI  - Chondroectodermal dysplasia.

PMID- 16883753
TI  - Catheter perforation of the superior vena cava.

PMID- 16883755
TI  - Symptomatic right coronary artery disease.

PMID- 16883757
TI  - Femur- fibula- ulna complex.

PMID- 16883756
TI  - Creutzfeldt-Jacob disease.

PMID- 16883758
TI  - Treacher-Collins syndrome.

PMID- 16883759
TI  - Eosinophilic granuloma of the skull.

PMID- 16883761
TI  - Dissection of the left internal carotid artery.

PMID- 16883760
TI  - Globular hemangioma of the calvaria.

PMID- 16883763
TI  - Pelvic gossypiboma and endometriosis.

PMID- 16883762
TI  - Hepatic amebic abscess complicated by Budd-Chiari syndrome.

PMID- 16883765
TI  - Breast implant rupture.

PMID- 16883764
TI  - High-grade non-Hodgkin lymphoma of shoulder.

PMID- 16883766
TI  - Peritoneal calcification as a complication of abdominal peritoneal dialysis.

PMID- 16883767
TI  - Thoracic spinal cord herniation and arachnoid cyst.

PMID- 16883769
TI  - Arteriovenous malformation of the left parietal lobe.

PMID- 16883768
TI  - Recurrent gastrointestinal stromal tumor (GIST).

PMID- 16883771
TI  - Rhabdomyolysis of the left upper leg after cocaine abuse.

PMID- 16883770
TI  - Schwannoma of left ulnar nerve.

PMID- 16883772
TI  - Spinal chordoma of the dorslumbar junction.

PMID- 16883773
TI  - Subperiosteal osteoid osteoma of the right acetabulum.

PMID- 16883775
TI  - MR imaging of spontaneous epiphyseal lesions of the knee: diagnosis and
      prognosis.

PMID- 16883774
TI  - Tracheobronchomegaly with bullous emphysema.

PMID- 16883776
TI  - Structure determination of neoefrapeptins A to N: peptides with insecticidal
      activity produced by the fungus Geotrichum candidum.
AB  - The structures of neoefrapeptins A to N, peptides with insecticidal activity,
      were elucidated. They showed a close similarity to efrapeptin. However, all
      neoefrapeptins contained the very rare amino acid 1-amino-cyclopropane-carboxylic
      acid and some of them also contained (2S,3S)-3-methylproline. The neoefrapeptins
      are the first case, in which these amino acids are found as building blocks for
      linear peptides. They were identified by comparison of the silylated hydrolyzate
      to reference material by GC/MS (EI-mode). The sequence was elucidated using mass
      spectrometry (ESI+ mode). Full scan spectra showed two fragments in high yield,
      even under mild ionization conditions. MS/MS spectra of these two fragments
      yielded fragment rich spectra from which the sequence of the compounds was
      determined almost completely. The proteolytic cleavage with the proteinase papain
      yielded products that allowed to prove the rest of the sequence and the identity
      of the C-terminus to efrapeptin. The proteolytic cleavage products allowed
      furthermore to determine the position of the isobaric amino acids, pipecolic acid
      and 3-methylproline in neoefrapeptin F, as well as the location of R-isovaline
      and S-isovaline. Papain digestion was such established as a tool for structure
      elucidation of peptides rich in alpha,alpha-dialkylated amino acids. CD spectra
      suggested a 3(10) helical structure for neoefrapeptins A and F.

PMID- 16883777
TI  - Relationship between cell morphology and intracellular potassium concentration in
      Candida albicans.
AB  - Previously we reported that valinomycin inhibited hyphal growth and induced
      growth as a chain of yeast cells under hyphal growth induction conditions in
      Candida albicans. To elucidate the hyphal growth inhibition by valinomycin, we
      examined the effect of various chemicals on the morphology and found that
      miconazole inhibited hyphal growth as well as valinomycin: both compounds
      promoted the leakage of potassium from cells. Analysis of intracellular potassium
      suggested that hyphal cells contain potassium at high concentrations in
      comparison with yeast cells. Hyphal growth inhibition by valinomycin was
      obstructed by the addition of serum. Potassium measurement showed that the
      addition of serum causes an increase in intracellular potassium, suggesting that
      the obstruction by serum might be due to an increase in intracellular potassium.
      The above-mentioned results strongly suggest that the addition of valinomycin and
      miconazole decreased interacellular potassium and this decrease inhibited hyphal
      transition.

PMID- 16883778
TI  - Isolation and insecticidal/anthelmintic activity of xanthonol, a novel bis
      xanthone, from a non-sporulating fungal species.
AB  - Xanthonol, a novel dimeric xanthone, was isolated from a fermentation broth of a
      non-sporulating fungal species using Sephadex LH20 followed by HPLC and the
      structure elucidated by spectral analysis. Xanthonol exhibited insecticidal and
      anthelmintic activities against larvae of Lucilia sericata, Aedes aegypti, and
      Haemonchus contortus with LD90 of 33, 8, and 50 microg/ml, respectively.

PMID- 16883779
TI  - Fluostatins C-E, novel members of the fluostatin family produced by Streptomyces
      strain Acta 1383.
AB  - Three new members of the fluostatin family, fluostatins C-E, were discovered in a
      culture filtrate extract of strain Acta 1383 during an HPLC screening program.
      The producing strain belongs to the genus Streptomyces and is closely related to
      type strains classified in the Streptomyces lavendulae 16S rRNA subclade.
      Fluostatins are named by their characteristic fluorenone chromophore. Fluostatin
      C shows moderate activity against selected human tumor cell lines.

PMID- 16883780
TI  - Biosynthesis of sespendole.
AB  - Sespendole is the first reported fungal metabolite having an indolosesquiterpene
      core structure. The biosynthesis of sespendole was studied here by feeding
      experiments with [13C]acetate, [15N]anthranilic acid and [13C]tryptophan. The
      data suggested that a farnesyl residue derived from the mevalonate pathway and an
      anthranilate-derived indole-3-glycerol phosphate residue are condensed, and then
      cyclization occurs along with rearrangement to form the indolosesquiterpene core.

PMID- 16883781
TI  - Enhanced activity of rifalazil in combination with levofloxacin, linezolid, or
      mupirocin against Staphylococcus aureus in vitro.
AB  - Rifalazil is a potent second-generation ansamycin that kills bacterial cells by
      inhibiting the beta subunit of RNA polymerase. Rifalazil has several improved
      properties compared with rifampicin, but retains rifampicin's propensity to
      develop resistant mutants at high frequency. To explore strategies to overcome
      resistance development, we studied the effects of rifalazil in combination with
      several different antibiotics in an in vitro time-kill model, against both log
      phase and stationary phase Staphylococcus aureus cells. Experiments were carried
      out at high initial cell density so that the frequency and proliferation of
      resistant mutants could be monitored. We found that each combination was
      advantageous in terms of enhanced killing and the suppression of mutants,
      compared with each drug used alone. None of the three combinations was effective
      against stationary phase cells.

PMID- 16883782
TI  - Kettapeptin: isolation, structure elucidation and activity of a new
      hexadepsipeptide antibiotic from a terrestrial Streptomyces sp.
AB  - The ethyl acetate extract of the Streptomyces sp. isolate GW99/1572 exhibited
      significant biological activity against Gram-positive bacteria and delivered
      kettapeptin (1), a new hexadepsipeptide antibiotic of the azinothricin type. The
      structure was elucidated by various 1D and 2D NMR techniques, mass spectrometry
      and by comparison of the NMR data with those of closely related antibiotics. The
      absolute configuration of the compound was derived by crystal structure analysis
      and by comparison with the optical rotation data of related compounds.

PMID- 16883783
TI  - Fogacin, a novel cyclic octaketide produced by Streptomyces strain Tu 6319.
AB  - A new octaketide named fogacin (1) was isolated from Streptomyces sp. (strain Tu
      6319). Furthermore two shunt metabolites, SEK4b (2) and anhydroSEK4b (3), were
      detected and identified as non-enzymatically cyclized products of polyketide
      intermediates built during the biosynthesis of actinorhodin. SEK4b (2) as well as
      anhydroSEK4b (3) were previously described as metabolites of genetically
      engineered strains.

PMID- 16883784
TI  - [Significance of some otologic function tests in diagnosis of Meniere's disease].
AB  - OBJECTIVE: To investigate the significance of vestibular function battery and
      electrocochleogram on diagnosis of Meniere's disease. METHOD: Patients with
      Meniere's disease were given pure tone hearing threshold test, auditory brainstem
      responses (ABR), electrocochleogram (ECoG), vestibular bithermal caloric test and
      vestibular evoked myogenic potentials (VEMP) test. RESULT: (1) As for the
      bithermal caloric test, the percentage of the abnormal canal paresis (CP) at
      three durations, i.e. , 0 to approximately 5 years, 6 to approximately 10 years
      and over 11 years were 56.9%, 75.9% and 61.6% respectively. The total positive
      rate was 50.0%. CP and duration of Meniere's disease had low correlation (P <
      0.05). (2) The percentage of the abnormal VEMP at three durations, i.e., 0-5
      years,6-10 years and over 11 years were 57.4%, 60% and 57.1% respectively. The
      total positive rate was 58.0%. The duration of Meniere 's disease with normal and
      abnormal VEMP had no significant difference( P >0.05). (3) The percentage of the
      abnormal ECoG at three durations, i.e., 0-5 years, 6-10 years and over 11 years
      were 72.1%, 73.3% and 81.3% (49/68,22/30 and 13/16) respectively. The total
      positive rate was 76.9%. The duration of Meniere's disease with normal and
      abnormal ECoG had no significant difference (P >0.05). CONCLUSION: Diagnosis of
      Meniere's disease is mainly based on the medical history. If it could combine
      with ECoG, bithermal caloric test and VEMP, the diagnosis would be earlier and
      more accurate.

PMID- 16883785
TI  - [Facial nerve monitoring in parotid gland surgery].
AB  - OBJECTIVE: To investigate the use and effect of facial nerve monitoring in
      parotid gland surgery. METHOD: Twenty-two patients with benign parotid tumor who
      received parotidectomy with continuous monitoring of the facial nerve were
      selected to analyse. RESULT: Each patient had a total resection of tumor without
      facial nerve paresis or sialocele formation. No recurrence was found during
      follow-up. CONCLUSION: Facial nerve monitoring is a useful tool in parotid gland
      surgery.

PMID- 16883786
TI  - [The artifacts and test-retest reliability of multiple auditory steady-state
      response].
AB  - OBJECTIVE: To investigate the characteristics and clinical application of
      artifacts and the test-retest reliability of multiple auditory steady-state
      response (MASSR). METHOD: The authors tested a group of healthy young volunteers
      and a group of patients with sensory hearing loss with the MASSR by analysing the
      rate of false negative artifacts (FNA) and their distribution. The healthy young
      volunteers were retested with MASSR several days after the first test to
      investigated the test retest reliability of MASSR. Furthermore, three cases of
      healthy young volunteers were retested in the sleeping status to explore the
      stability of MASSR threshold and the influence of sleep. RESULT: (1) The FNA
      mainly distributed in low frequencies districts and the intensities were near
      threshold, no remarkable differences could be seen between the normal ears and
      the ear with sensory hearing loss. The FNA disappeared when the volunteers were
      asleep. (2) The test-retest variability was much higher in 0.5 kHz than in other
      frequencies. The variable range was 0 - 30 dB in 0.5 kHz, and there was test
      retest reliability in 1.0-4.0 kHz. (3) The artificial response was present when
      using strong stimulus for the patients with profound hearing loss. When MASSR was
      recorded in awake condition, the FNA appeared. When using strong stimulus for the
      cases with profound hearing loss, the artificial response existed and the test
      retest variabilities were large. The whole test duration was often much longer
      than the auditory brainstem response (ABR) and 40 Hz auditory evoked potential
      (40 Hz AEP). CONCLUSION: As an objective auditory evaluation method, MASSR
      scarcely has superior characteristics to ABR and 40 Hz AEP.

PMID- 16883787
TI  - [The measurement of pneumatized mastoid and facial recess in cochlear implant
      recipients younger than three years old].
AB  - OBJECTIVE: To evaluate the postnatal growth of mastoid air cells and facial
      recess and the implications for cochlear implantation in very young children.
      METHOD: Thirty-two pediatric cochlear implant recipients younger than three years
      were enrolled in this study. Before implantation, pneumatized mastoid and facial
      recess were measured by high resolution computed tomography (HRCT) and compared
      with direct anatomical measurement in implantation. RESULT: We found the similar
      result in two measurements. All recipients had facial recess and there was no
      significant difference of the volume between the recipients in this study and the
      children in another group who were older than seven years old (P >0.05). The size
      of pneumatized mastoid was significantly different between recipients younger
      than 16 months and those older (P <0.05). CONCLUSION: (1) HRCT is very clinically
      valuable in making accurate diagnosis and surgical plan. (2) The facial recess is
      already adult size in children younger than three years old. (3) The size of
      pneumatized mastoid may affect mastoidectomy in cochlear implantation in very
      young children.

PMID- 16883788
TI  - [Evaluation of tympanoplasty with reconstruction of the external canal after
      mastoidectomy for cholesteatoma].
AB  - OBJECTIVE: To investigate the method to repair the deletion of external canal and
      opened mastoid space after mastoidectomy. METHOD: One stage tympanoplasty with
      reconstruction of the external canal with temporal cortex was completed in 58
      cases (58 ears) with cholesteatoma. RESULT: During the follow-up ranging from one
      to three years, there was only one relapse. The configuration of external canal
      was almost normal and pneumatic mastoid space was maintained. Hearing was
      improved over 30dB in five ears, 20 to 29 dB in 11 ears, 10 to 19 dB in 30 ears,
      less 10 dB in eight ears and hearing wasn't improved in four ears. CONCLUSION:
      One stage tympanoplasty with reconstruction of the external canal after
      mastoidectomy for cholesteatoma is a practical way to improve hearing and
      decrease recurrence.

PMID- 16883789
TI  - [Follow-up examination for newborns and infants who failed hearing screening].
AB  - OBJECTIVE: To investigate the hearing change and the characteristic of hearing
      thresholds of the infants failing in the hearing screening. METHOD: ABR,DPOAE and
      acoustic immittance were used to test infants failing in the screening in their
      third month and the sixth month, whose results were compared. RESULT: In the
      third month the false positive rate of DPOAE test was 9.6%. Comparing with the
      results tested in the third month, the degree of severe hearing loss retested in
      the sixth month did not change much. But the percentage of the slight-moderate
      hearing loss improvement to normal or better was higher. Comparing ABR threshold
      result in the third month and that in the sixth month, t = 3.496, P <0.01 in the
      left ear, and t = 5.572, P <0.01 in the right ear, respectively. There was
      significant difference between these results. CONCLUSION: The new-borns failing
      DPOAE can not be just considered to identifying hearing loss,and it must be with
      the ABR to make the diagnosis. It is feasible to diagnose severe-profound hearing
      loss in the third month and interfere before the sixth month, but the infants
      with mild-moderate hearing loss must undertake the auditory tests more than twice
      and be followed up in more than half a year, then we can make diagnosis according
      to the audiologic evaluations results and the daily behaviors.

PMID- 16883790
TI  - [The measuring of ECP and IgE in middle ear effusion of patients with otitis
      media of effusion].
AB  - OBJECTIVE: To study the relationship between otitis media of effusion (OME) and
      allergy by investigating eosinophil cationic protein in middle ear effusion (
      MECP), middle ear effusion IgE (MIgE) and serum eosinophil cationic protein
      (SECP). METHOD: The specimens drawn from 31 patients of OME were tested with Uni
      CAP-100 allergic antigen testing system for the MECP, IgE and SECP. The results
      then were analyzed by statistical methods. RESULT: MECP were found in all the
      effusion specimens of 31 patients, the average concentration of which was 56.88
      microg/L. The MECP concentration level in nine specimens (28.1%) was
      significantly elevated. The average concentration of MIgE was 27.2 ku/L. The MIgE
      concentration level in three specimens (9.7%) was remarkably increased. There was
      a positive correlation between the MECP level and the MIgE level( P <0.05). The
      average concentration of SECP was 5.6 microg/L. CONCLUSION: ECP exists in the
      middle ear effusion of OME. OME is an allergic inflammatory process more
      localized in middle ear itself in some patients. There may be a complicated
      allergic mechanism in OME.

PMID- 16883791
TI  - [Evidence-based treatment of secretory otitis media in patients with
      nasopharyngeal carcinoma after radiotherapy].
AB  - OBJECTIVE: According to the principle of Evidence-Based Medicine (EBM), to
      analyse the cause of SOM in patients with nasopharyngeal carcinoma (NPC) after
      radiotherapy and to explore the effective treatment methods of SOM in patients
      with NPC after radiotherapy. METHOD: One hundred and six cases (112 ears) of SOM
      in patients with NPC after radiotherapy were treated with comprehensive
      management,e. g application of general and local antibiotics,nerves nutrition
      medicine, blood vessel dilating drugs and hormone, reinforced clearance of nasal
      cavities and nasopharynx and treatment of the disease of nasal cavities and
      sinuses, in addition to inserting catheter into the tympanum and intratympanic
      application of medicine through the eustachian tube. RESULT: Before the
      comprehensive treatment, all patients had hearing impairment, tinnitus and/or the
      feeling of ear blocked. Acoustic immittance test showed 112 ears(100%) had Type B
      tympanogram. After the treatment, tinnitus (ears) disappeared in 81 ears
      (72.32%), relieved in 25 ears (22.32%) and no effect was seen in 6 ears (5.36%).
      The total efficiency was 94.64. The feeling of ear blocked disappeared in 92 ears
      (82.14%), relieved in 18 ears (16.07%) and no effect was found in 2 ears (1.79%).
      The total efficiency was 98.21%. Acoustic immittance test showed 56 ears (50%)
      had Type A tympanogram, 42 ears had Type As (37.50%), 2 ears had Type B (1.79%)
      and, 12 ear had Type Cs (10.71%). The mean hearing threshold of 0.5,1,2 kHz of
      pure-tone was (28.5 +/- 3.0) dBHL after the treatment, which was (47.0 +/- 5.0)
      dBHL prior to it. No otorrhea, or permanent scar obstruction in the eustachian
      tube was found after the treatment. CONCLUSION: It is very effective and
      practicable to treat SOM in patients with NPC after radiotherapy according to the
      principle of EBM and to aim directly at the cause of SOM in patients with NPC
      after radiotherapy. It is very significant to improve the life quality of
      patients with NPC after radiotherapy.

PMID- 16883792
TI  - [Expression of tumor suppressor gene PTEN in laryngeal carcinoma and its clinical
      significance].
AB  - OBJECTIVE: To investigate the expression of tumor suppressor gene PTEN in
      laryngeal carcinoma and study its clinical-pathological implication and its
      clinical significance. METHOD: The expression of PTEN was detected by
      immunohistochemistry SP(Streptavidin peroxidase) method in 68 cases of laryngeal
      carcinoma, 33 cases of adjacent normal laryngeal mucosa. RESULT: (1) There was
      61.8% (42 of 68) of cases with expression of PTEN in the tumor tissues, and
      100.0% of cases (33 of 33) with the expression of PTEN in the normal mucosa. The
      positive expression of PTEN in the laryngeal carcinoma gorp was remarkably lower
      than that in the control group. ( P <0.01). (2) The positive expression of PTEN
      in high and middle degree of differentiation group was significantly higher than
      that in low degree of differentiation(79.3% vs 48.7%). Tumors with lymph node
      metastases(55.0%) had less PTEN protein expression than those without
      metastasis(71.4%) (P <0.05). As for the PTEN expression between I + II stage and
      III + IV stage, the difference was significant (76.0% vs 53.5%)(P <0.05). The
      positive rates of PTEN decreased with clinical stage, the poor differentiation,
      deep invasion and lymph nodes metastasis ( P <0.05). PTEN protein expression had
      no relation to the patients' age, sex, tumor size and location (P >0.05).
      CONCLUSION: PTEN gene plays an important role in the occurrence and development
      of laryngeal carcinoma. It is suggested that PTEN can be a useful marker for
      predicting invasion and metastasis ability of laryngeal carcinoma.

PMID- 16883793
TI  - [Application of portable esophageal dilator in treatment of esophageal stenosis
      at home].
AB  - OBJECTIVE: To explore an economical protocol for esophageal stenosis treatment at
      home and evaluate the effects of portable esophageal dilator. METHOD: Sixty-seven
      patients with esophageal stenosis were treated at home by themselves with
      portable esophageal dilator, which was designed by Prof Wang HT, one of the
      authors. Twenty-nine cases of esophageal stenosis were caused by chemical damage,
      23 cases by esophageal tumor, 13 postoperation cases with hypopharyngeal and
      upper esophageal tumor and two cases by laryngeal thyroid gland recurrent tumor.
      Stricture happened at esophageal entrance and upper segment in 15 cases, at
      middle in 32 cases, both at middle and upper in 17 cases and at whole length of
      esophagus in three cases. Stricture was not complete atresia and dilators could
      insert into esophagus in all patients. RESULT: Significant effects were found in
      43 patients and good effects in 24 patients. Seven deaths were caused by remote
      metastasis of recurrent cancer resulting in multiple organ failure or large blood
      vessels bleeding resulting of tumor erosion. Follow-up visit ranged from the
      shortest period of four months to the longest period of five years and 1 month,
      9.8 months on average. CONCLUSION: Family portable dilator and self-catering
      dilation is an effective and safe method for treating esophageal stenosis. It is
      so simple, convenient, painless with low expense that it is especially useful in
      countryside hospitals and undeveloped rural areas.

PMID- 16883794
TI  - [Establishment of conditionally immortalized rat cochlear greater epithelial
      ridge and lesser epithelial ridge cell lines using a retrovirus-mediated gene
      transfer technique].
AB  - OBJECTIVE: To facilitate further investigation of the function of greater
      epithelial ridge (GER) and lesser epithelial ridge (LER) cells, a greater a
      lesser epithelial ridge cell immortal line originated from postnatal rat cochleae
      were established. METHOD: The GER and LER cells were dissected from P1 rats
      cochleae and infected with SV40-LT antigen using a retrovirus-mediated method.
      The established cell lines were purified by monoclone technique and identified
      following morphology observation and immunocytochemical staining. RESULT: The
      established cell lines had been stably maintained continuously for more than 20
      passages and displayed many features similar to epithelial cells. They grew in
      patches and assumed a polygonal morphology. Immunocytochemical characterization
      revealed that these cells could be labeled by GER/LER marker (Isletl) and SV40-LT
      antigen. CONCLUSION: In the present experiment, the GER and LER cell line from
      postnatal rat cochleae has been successfully established and this cell line may
      potentially provide an invaluable system for studying hair cell differentiation
      and regeneration as well as the therapy of sensory deafness caused by auditory
      hair cells loss.

PMID- 16883796
TI  - [Soil carbon cycle of Pinus tabulaeformis forest in Huoditang forest region of
      Qinling Mountains].
AB  - With soil carbon cycle compartment model,this paper studied the carbon storage
      and flux of each carbon compartment of soil under Pinus tabulaeformis, a main
      forest type in the Huoditang forest region of Qinling Mountain. The results
      showed that the storage of soil organic carbon was 146.071 t x hm(-2), with
      130.366 t x hm(-2) in mineral soil layer and 12.626 t x hm(-2) in litter layer.
      The storage was lower than the average value of forest soils in China and of oak
      Sharptooth forest soil in Huoditang, but higher than that of the soils under
      temperate coniferous forest and tropical forest. The annual carbon input into
      litter layer was 5.939 t x hm(-2), with 56.9% from above-ground litter and 43.1%
      from underground dead roots, while that into mineral soil layer via humic acid
      was 2. 034 t x hm(-2). The annual amount of carbon released from the respiration
      of P. zabulaeformis forest-soil system was 14. 012 t x hm(-2), with litter layer,
      mineral soil layer, dead root system, and live root system occupied 15.7%, 14.5%,
      11.7% and 58.1%, respectively.

PMID- 16883795
TI  - [Application of rat tail collagen in the primary culture of rats marginal cells
      of stria vascularis].
AB  - OBJECTIVE: To study the feasibility of application of rat-tail collagen in the
      primary culture of rats marginal cells of stria vascularis. METHOD: The effect of
      self-made rat-tail collagen on the primary culture of rats marginal cells of
      stria vascularis was observed and estimated. RESULT: When cochlear stria
      vascularis fragment was isolated and cultured for 24 h, a few culture cells
      appeared around the fragments. About 48 to approximately 72 h later, clusters of
      culture cells could be seen,these cells showed the cobblestone shape under the
      microscope. The immunohistochemistry and the transmission electron microscopy
      showed the epithelial origination of these cells. CONCLUSION: It is feasible to
      the primarily culture the rats marginal cells of stria vascularis with self-made
      rat-tail collagen.

PMID- 16883797
TI  - [Effects of Robinia pseudoacacia roots on deep soil moisture status].
AB  - The study on the root distribution characters of Robinia pseudoacacia and soil
      moisture status in the Loess Plateau showed that on shady slope, there was no
      obvious difference in the horizontal distribution of R. pseudoacacia fine roots
      within 2.0 m from the stem, and the maximal distribution depth of the roots could
      reach 2.0 m. In sunny slope, the vertical distribution of the roots within 0.5 m
      from the stem could also reach that depth. The root amount in shady slope was
      larger than that in sunny slope, and the affected depth of R. pseudoacacia roots
      on soil moisture status reached 3.3 m in shady slope, while 2.7 m in sunny slope.

PMID- 16883798
TI  - [Impact of soil cadmium contamination on chlorophyll fluorescence characters and
      biomass accumulation of four broad-leaved tree species seedlings].
AB  - In a greenhouse pot experiment,a gradient of soil Cd concentration was
      established by adding 0,50,100 and 200 mg CdCl2 x kg(-1) air-dried soil, and the
      seedlings of one-year-old Rosa davurica, Philadelphus schrenkii, Acer mandshurica
      and Lonicera maackii were transplanted. The measurement of the seedlings'
      chlorophyll fluorescence parameters and biomass accumulation after 70 days of
      transplanting showed that with increasing soil Cd content, all the test tree
      species had a decrease of Fv/Fm, phi(PSII), qP and biomass, but an increase of
      qN. A. mandshurica had the greatest responses, followed by P. schrenkii and L.
      maackii, and R. davurica. The tolerance of these tree species to soil Cd
      contamination followed the order of R. davurica > P. schrenkii and L. maackii >
      A. mandshurica.

PMID- 16883799
TI  - [Responses of microbes in rhizospheric soil of Abies faxoniana to elevated
      atmospheric CO2 concentration and temperature].
AB  - With independent and top-enclosed chamber system, this paper studied the
      responses of culturable bacteria, fungi, and actinomycetes in rhizospheric soil
      of Abies faxoniana sapling to elevated atmospheric CO2 concentration (ambient
      +350( +/- 25) [micromol x mol(-1), EC), temperature (ambient + 2. 2 (+/- 0.5)
      degrees C; ET), and their combination (ECT) under high-frigid conditions of West
      Sichuan Province. The results showed that in comparing with the control,
      treatments EC and ET increased the number of rhizospheric bacteria by 35%, 164%
      and 312%, and 30%, 115% and 209% in June, August and October, respectively, but
      had little effects on the numbers of rhizospheric actinomycetes and fungi. In
      treatment ECT, the numbers of rhizospheric actinomycetes and fungi increased by
      49%, 50% and 96% ,and 151%, 57% and 48% in June, August and October,
      respectively, while that of rhizospheric bacteria had little variation. EC, ET
      and ECT had significant effects on the total number of rhizospheric microbes,
      with the R/S being 1.93,1.27 and 1.46, respectively,but had little effects on non
      rhizospheric microbes.

PMID- 16883800
TI  - [Effects of mulching and intercropping on temporal-spatial variation of soil
      temperature in tea plantation in subtropical hilly region].
AB  - The study of four years straw mulching and white clover intercropping in a tea
      plantation in subtropical hilly region showed that the soil temperature in the
      plantation presented a distinct dynamic temporal-spatial variation and
      hysteresis, which was greatly accorded with the fittest temperature of tea
      growth. Straw mulching and white clover intercropping altered the nature of soil
      thermal exchanging layer (soil surface), decreased daily temperature difference,
      enhanced the temperature stability in the same soil layer, and had duplex effects
      of lowering temperature when it went up and increasing and keeping temperature
      when it went down. The effectiveness was in the order of white clover
      intercropping > straw mulching > control, 13:00 > 19:00 >7:00,and lowering
      temperature > increasing and keeping temperature, and decreased with soil depth.
      Straw mulching and white clover intercropping adjusted the switching point of the
      temporal-spatial variation of soil temperature, and evidently decreased the
      emergence of harmful high temperature. During the period of continual high
      temperature, these measures markedly lowered soil temperature, and effectively
      shortened the duration of this period.

PMID- 16883801
TI  - [Responses of changium smyrnioides seedlings survival and growth to light
      intensity].
AB  - Changium smyrnioides, a monotypic species in Umbellaceae, can only be found in
      Yangtze Rive basin in China, and its seedlings are rare in natural habitats. The
      study on the effects of light intensity on C. smyrnioides seedlings survival and
      growth showed that the seedlings had the highest survival rate under higher light
      intensity (65% of direct sun light) but the lowest one under 25% of direct sun
      light, indicating that medium light intensity was propitious to seedlings
      establishment. The seedlings growth of C. smyrnioides was also the best under 65%
      of direct sun light, showing the maximum values of growth rate, total leaf area,
      leaf biomass, root biomass, and total biomass. Low temperature pregermination
      gave five times higher seedlings biomass than normal germination, and helped the
      seedlings enduring disadvantageous environment, which provided a new approach to
      planting and protecting C. Smyrnioides.

PMID- 16883802
TI  - [Spatial heterogeneity of soil moisture in Shapotou sand-fixing artificial
      vegetation area].
AB  - To explore the characteristics of soil moisture heterogeneity in sand-fixing
      artificial vegetation area is of significance in vegetation recovery and
      environment control in arid regions. With the methods of traditional statistics
      and geo-statistics, this paper studied the heterogeneity of soil moisture in the
      layers from 0 to 200 cm in depth in Shapotou sand-fixing vegetation area. The
      results showed that the variation of soil moisture in layers of 160 to
      approximately 180 and 180 to approximately 200 cm was relatively larger, with the
      variation coefficient being 0.72 and 0.73, respectively, and the next was in top
      layer (0 to approximately 5 cm ), with a variation coefficient of 0.66. Semi
      variance analysis showed that the autocorrelation of soil moisture spatial
      heterogeneity in total spatial heterogeneity was high, ranging from 87.7% to
      99.9%. The scale of spatial heterogeneity in different soil layers was different,
      with the minimum in 60 to approximately 80 cm layer and the maximum in 20 to
      approximately 40 cm layer, but no regular changes being observed from surface to
      deep layers. The colorful contour maps of Kriging interpolation indicated that
      the variation of soil moisture was larger in 0 to approximately 140 cm layer than
      in 140 to approximately 200 cm layer. The correlation between semi-variance and
      distance in four directions of 0 degrees, 45 degrees ,90 degrees and 135 degrees
      was weak, suggesting that the variation of soil moisture was independent, random,
      and homogeneous.

PMID- 16883803
TI  - [Protective effects and their mechanisms of cobalt on soybean seedling's leaf
      under drought stress].
AB  - This paper studied the effects of cobalt on the polyamine content, reactive
      oxygen level, anti-oxidative enzyme activity, and cell membrane permeability of
      soybean seedling's leaf under drought stress, and discussed the mechanisms of
      these effects. The results showed that under drought stress, cobalt at its
      concentration of 30 micromol x L(-1) could significantly inhibit the production
      of ethylene. This concentration of cobalt had no significant effects on the
      contents of MDA and chlorophyll when the drought stress lasted 0 to approximately
      12 days, but significantly restrained the increase of reactive oxygen level,
      hampered the decline of putrescine, spermidine and spermine contents and anti
      oxidative enzyme activities,and thus,inhibited the accumulation of MDA and
      alleviated the reduction of chlorophyll content when the stress lasted 15 to
      approximately 21 days. It could be concluded that when soybean seedling's leaf
      was deeply stressed and damaged under drought stress, cobalt could alleviate the
      decline of polyamine content and anti-oxidative enzyme activity,and hence,
      alleviate the increment of reactive oxygen level and cell membrane's damage
      degree through inhibiting the production of ethylene, and exerted its protective
      effects on the soybean seedling's leaf under drought stress.

PMID- 16883804
TI  - [Effects of irradiance on boron requirement of phaseolus aureus cutting for its
      adventitious root development].
AB  - This paper studied the boron requirement of Phaseolus aureus cutting for its
      adventitious root development under different photosynthetic active radiation
      (PAR). The results showed that exogenous boron supply was necessary for the
      adventitious root development of the cutting under 10 days of PAR at 50 or 100
      micromol x m(-2) x s(-1), but unnecessary under 6 days of this irradiance and
      followed by 4 days of darkness. Exogenous boron supply was also necessary for the
      rooting under 6 days of PAR at 180 micromol x m(-2) x s(-1) and followed by 4
      days of darkness. When the PAR at 100 micromol x m(-2) x s(-1) was employed for
      10 days, the amount of soluble boron in each hypocotyl of the cutting was only
      half of that under 6 days of this irradiance and followed by 4 days of darkness,
      which might be the reason of the necessity of exogenous boron supply for the
      rooting under 10 days of PAR at 100 micromol x m(-2) x s(-1).

PMID- 16883805
TI  - [Effects of different furrow irrigation modes on grape growth and water use in
      oasis region].
AB  - In this paper, a field experiment was conducted in the oasis region of Hexi
      Corridor, Gansu Province to study the effects of alternate partial root zone
      furrow irrigation (AFI) and conventional furrow irrigation (CFI) on grape growth
      and water use under mulching and no mulching. The results indicated that AFI,
      either mulching or no mulching, could alternately keep a part of root zone drying
      and another part of it wetting, which induced the compensative growth of grape.
      Under AFI, more leaf stomas closed. The photosynthesis rate was less affected,
      but the transpiration rate decreased obviously, and the water use efficiency
      increased. It was suggested that AFI, especially combined with film mulching,
      could regulate the behaviors of leaf stoma, and promote grape growth and water
      use, being an effective approach in cultivating grape in the field.

PMID- 16883806
TI  - [Simulation of greenhouse tomato dry matter partitioning and yield prediction].
AB  - Based on the relationships between dry matter partitioning index, harvest index,
      and product of thermal effectiveness and PAR, a simulation model for greenhouse
      tomato dry matter partitioning and yield prediction was built, and validated by
      independent experimental data of different cultivars, substrates and locations.
      The coefficient of determination (R2) between simulated and measured shoot, root,
      stem, leaf and fruit dry matter weight based on 1:1 line was 0.95, 0.57, 0.82,
      0.79 and 0.93, the root mean squared error (RMSE) between them was 647.0, 78.1,
      279.0, 496.9 and 381.8 kg x hm(-2), and the R2 and RMSE between predicted and
      measured yield based on 1:1 line were 0.88 and 5 828.5 kg x hm(-2), respectively.
      Compared to 'source-sink' theory, the model developed in this study could give
      satisfactory prediction of the dry weight of leaf, stem, fruit and yield, with
      fewer parameters that could be easily obtained in practice.

PMID- 16883807
TI  - [Changes of crop yield and soil fertility under long-term fertilization and
      nutrients-recycling and reutilization on a black soil: IV. Soil organic carbon
      and its fractions].
AB  - A long-term experiment was conducted on a black soil of Northeast China to study
      the effects of applying chemical fertilizers and recycled organic manure (ROM) on
      the changes of soil organic carbon and its fractions. The results showed that
      from 1985 to 2004, soil total organic carbon (TOC) decreased by 7.83% in
      control,4.56% in N application, 1.61% in N + P application, and 5.56% in ROM
      application, but increased by 0.33% in N + P + K application. Comparing with
      single application of ROM, its application with chemical fertilizers, i. e., N +
      ROM, N + P + ROM, and N + P + K + ROM, increased the TOC concentration by 0.35%,
      1.05% and 0.64%, respectively. The readily oxidized carbon (ROC) in fertilization
      treatments was increased by 8.64% to approximately 28.4%, and the increment was
      higher in treatments of chemical fertilizers plus ROM than in treatments of
      chemical fertilizers. The ROC was significantly correlated with soil TOC (Y =
      14.192X + 23.9, R2 = 0.802) and stalk yields (Y = 19032X - 7950.6, R2 = 0.759).
      Light fraction organic carbon (LF-C) had the same trends with ROC. After 20 years
      fertilization, the organic carbon in soil humic acid and fulvic acid was
      decreased by 1.64% to approximately 26.23% and 2.33% to approximately 28.68%,
      respectively, but in treatments of chemical fertilizers plus ROM, the decreasing
      trend was slowed down.

PMID- 16883808
TI  - [Effects of abscisic acid on photosynthetic characteristics and antioxidant
      enzyme activities of wheat seedlings].
AB  - This paper studied the effects of short- and long term abscisic acid (ABA)
      treatments on the CO2 assimilation (Pn), carboxylation efficiency (CE), response
      of Pn to CO2, and antioxidant enzyme activities of wheat seedlings exposed to UV
      C. The results showed that under no UV-C, short- and long term ABA treatments
      increased Pn by 14.69% and 20.46%, and decreased stomatal conductance (Gs) by
      14.74% and 17.31%, respectively, compared to the control, while no effects were
      observed on intercellular CO2 concentration (Ci) and CE. Under UV-C, the Pn, CE,
      Gs and Ci decreased, with the least decrease in long term ABA treatment, less in
      short term ABA treatment, and the most in control. ABA could increase the
      response of Pn to CO2, while UV-C inhibited it. In ABA treatments, antioxidant
      enzyme activities were enhanced, while MDA content was decreased. Under UV-C, CAT
      activity increased first, reached its maximum after 1 h, and decreased then. The
      activities of SOD and POD in ABA treatments increased first and decreased then,
      with the greater increase in long term ABA treatment than in short term ABA
      treatment, while those in the control decreased. It was suggested that through
      enhancing Pn and antioxidant enzyme activities, ABA could enhance the resistance
      of wheat to UV-C, and long term ABA treatment had better effects than short term
      ABA treatment.

PMID- 16883809
TI  - [Effects of specific microbial biocides on N transformation in soil with glucose
      amendment].
AB  - In an incubation test of soil with glucose amendment, two kinds of nitrogenous
      fertilizer and three kinds of specific microbial biocides were applied, and the
      contents of soil NH(4+)-N, NO3(-)-N, glucosamine and muramic acid were measured
      to differentiate the relative contribution and timing characteristics of soil
      microbes in nitrogen immobilization. The results showed that penicillin and
      streptomycin decreased the transformation rate of NH(4+)-N markedly, with more
      significant effects than actidione. The amount ratio of glucosamine to muramic
      acid after applying penicillin and streptomycin rapidly increased first, and
      tended to equilibrium then. With the application of actidione, the transformation
      rate of NO3(-)-N decreased continuously, and the synthesis of glucosamine was
      inhibited, while penicillin and streptomycin had no significant effects on them.
      At the early stage of incubation, bacteria could rapidly immobilize both NH(4+)-N
      and NO3(-)-N, with NH(4+)-N preferred, while at the later stage of incubation,
      fungi were the dominant contributor to nitrogen transformation, and had much
      stronger ability of utilizing NO3(-)-N than bacteria.

PMID- 16883810
TI  - [Effects of long-term localized fertilization on soil humus combining form in
      sheltered vegetable field].
AB  - The study showed that on a sheltered vegetable field, a long-term application of
      organic plus chemical fertilizers induced a higher content of loosely combined
      soil humus than applying chemical fertilizers alone, while there was no
      significant difference in firmly combined humus content among different
      fertilization treatments. More tightly combined humus was observed in organic
      fertilizer treatments than in chemical fertilizer treatments, and the highest
      content (11.53 g x kg(-1)) was in the treatment of organic fertilizer plus
      chemical NPK. The ratio of loosely/tightly combined humus tended to decrease
      after a long-term application of organic fertilizer, being the lowest (1.10) in
      the treatment of organic fertilizer plus chemical NPK.

PMID- 16883811
TI  - [Photosynthetic characters and fluorescence parameters of different grape stocks
      under water stress].
AB  - The study showed that water stress decreased the net photosynthetic rate (Pn),
      stomatal conductance (Gs), Tr transpiration rate (Tr), maximum fluorescence (Fm),
      ratio of variable to maximum fluorescence (Fv/Fm), and actual activities of PS II
      (phiPS II), but increased the minimal fluorescence (Fo). The alterations of test
      parameters differed with grape stocks. Under adequate water supply and mild water
      stress, the Pn of 3309C was higher than that of 1103P and 420A, while the
      chlorophyll fluorescence parameters of these three stocks changed a little. Under
      moderate water stress,the Pn of 1103P was higher than that of 420A and 3309C,the
      Fo of 3309C increased by 17.1% while Fv/Fm decreased by 8.5%, and the Fo of 1103P
      increased by 6.8% while Fv/Fm decreased by 5.8%. Under severe water stress,the Pn
      of 1103P was the highest (5.6 micromol x m(-2) x s(-1)), which was 24% higher
      than that of 3309C, and the water use efficiency of 1103P was about 1.95 times as
      high as that of 3309C. The Fo of 3309C increased by 36.2% while Fv/Fm decreased
      by 20.1%, and the Fo of 1103P increased by 9. 9% while Fv/Fm decreased by 10.2%.
      It was implied that there was a close correlation between drought-resistance and
      the alteration of photosynthetic characters and chlorophyll fluorescence
      parameters, of which, the correlation index of Fv/Fm and Pn was the highest (r =
      0.9883).

PMID- 16883812
TI  - [Relationships between row crop evapotranspiration and two sources- energy
      partition and exchange under non-water stress condition].
AB  - With the maize harvested for green fodder and grown at the Hunshandake sand area
      as test row crop,and by combining two sources- energy balance model with dual
      crop coefficient approach presented in FAO-56,this paper estimated the available
      energy partitioned into two sources, canopy and soil surface (Ac and As), and the
      latent and sensible heat fluxes, lambdaEc, lambdaEs, Hc and Hs. The results
      showed that under non-water stress condition, the interaction between Hc and
      lambdaEc made canopy absorbed a micro-advection to enhance transpiration
      expressed by latent heat flux,with the value of (lambdaE(i)c-A(i)c). The greatest
      enhancement of transpiration occurred at the crop development stage with leaf
      area index between 0.6 and 2.4, and the average of the enhancement was 4.32 MJ x
      m(-2) x d(-1). Soil evaporation was in progress with a rate below the available
      energy of soil, due to the interaction between Hc and lambdaEc under non-water
      stress condition, except a few days immediately after heavy rain. The evaporation
      rate depended on the percentage of soil available energy dissipated as latent
      heat flux. The average value of minimum percentage, 11.5%, occurred at mid-season
      stage,while that of maximum percentages,51.9%, occurred at initial stage. Latent
      heat fluxes were the important components of energy exchange during the process
      of evapotranspiration. The available energy dissipated as latent heat fluxes of
      the two sources during crop development, mid-season, and late season stages
      accounted for over 83% of the total energy.

PMID- 16883814
TI  - [Effects of light intensity on resveratrol and polydatin production in Rumex
      gmelini root].
AB  - The study under controlled conditions showed that short-term shading resulted in
      the increase of resveratrol and polydatin contents in Rumex gmelini root, while
      long-term shading led to the decrease of them. The increase and decrease were
      more obvious with increasing shading degree and time. The production of
      resveratrol reached the maximum in August, while that of polydatin was in
      September. Shading had a negative effect on the resveratrol and polydatin
      accumulation in R. gmelini root, but severe shading at the late growth period of
      R. gmelini increased the production of resveratrol and polydatin.

PMID- 16883813
TI  - [Allelopathy of aqueous extract from Ligularia virgaurea, a dominant weed in
      psychro-grassland, on pasture plants].
AB  - Ligularia virgaurea is a noxious weed widely distributed in the alpine grassland
      of east Qinghai-Tibet Plateau of China. This paper studied the allelopathy of its
      aqueous extract on the pasture plants Festuca sinensis, Bromus magnus, Elymus
      nutans, Poa annua, and F. ovina in the region. The mean response index (RI)
      values of the pasture plants were calculated, and used to quantitatively assess
      the allelopathic sensitivity of the receptors at three levels, i. e., growth
      items, development stages, and species. Corresponding values of the weed were
      also treated in similar way to assess the allelopathic potential of the donor.
      The results showed that the allelopathic sensitivity was in the order of P. annua
      > B. magnus > F. sinensis > F. ovina > E. nutans. Both the seed germination and
      the seedling growth of test pasture plants were inhibited at species level,
      suggesting that rain eluviation was one of the means by which the weed released
      allelochemicals. The aqueous extracts from L. virgaurea root and leaf had a
      significant inhibitory effect at species level, and the effect of root extract
      was stronger than that of leaf extract, suggesting the competition among species
      on the underground resources in natural grassland. Allelopathy played an
      important role in L. virgaurea invasion, and might be responsible to the
      formation of mono-dominant community and the degeneration of grassland.

PMID- 16883815
TI  - [Long-term effects of different planting proportion on forest landscape in Great
      Hing' anling Mountains after the catastrophic fire in 1987].
AB  - With LANDIS model, this paper simulated the long-term dynamics of 100% larch (P1)
      70% larch and 30% Mongolian Scotch pine (P2), 50% larch and 50% Mongolian Scotch
      pine (P3), 30% larch and 70% Mongolian Scotch pine (P4), and 100% Mongolian
      Scotch pine (P5) in the Tuqiang Forest Bureau at the northern slope of Great
      Hing' anling Mountains after the catastrophic fire in 1987, taking the forest
      under natural regeneration as the reference. The results showed that at the
      early, medium, and late stages of succession, different planting proportion all
      had significant effects on the abundance of larch, Mongolian Scotch pine, and
      white birch. The abundance of larch increased with time,while that of Mongolian
      Scotch pine was in a converse way. Larch and Mongolian Scotch pine had an
      increased abundance with their increasing planting proportion, but the abundance
      of white birch was higher under natural regeneration than under different
      proportions of planting. The abundance of white birch was positively affected by
      the planting proportions of larch and Mongolian Scotch pine. As for the total
      abundance of larch and Mongolian Scotch pine, it had no significant difference
      under P2, P3 and P4, but was higher than that under P1 and P5, indicating that
      individual-species planting should not be used in the forest landscape.

PMID- 16883816
TI  - [Land use and land cover changes and driving forces in the upper reach of
      Minjiang River].
AB  - The upper reach of Minjiang River is the representative of mountainous area in
      Southwest China in the aspects of natural environment, ecosystem structure,
      economic development, and social culture. The characteristics of the dynamic
      changes of its land use and land cover stood for the common questions occurred in
      the land resources and usage of this area. Woodland and grassland are the main
      types of land use and land cover, and many changes in land use/cover types
      happened from 1974 to 2000. Among forestland, shrub land, economic forestland,
      grassland, cropland and resident land,changes mainly happened between woodland
      and grassland, and all occurred bilaterally. The area of forestland changed
      mostly and kept decreasing from 1974 to 2000, while that of other land types
      increased. The changes of land use and land cover happened between 1974 and 1986
      were larger than those happened between 1986 and 2000. Population and economy
      were the main driving factors for the changes of land use and land cover in the
      upper reach of Minjiang River. Since the programs of Natural Forest Protection
      and Withdrawing Cropland to Woodland and Grassland carried into execution, the
      land use and land cover have changed rationally.

PMID- 16883817
TI  - [Theoretical analysis of ecological diversity models and their application in
      Fukang of Xinjiang Uygur Autonomous Region].
AB  - Ecological diversity refers to a combination of the richness and evenness of an
      investigation object. Based on this, the widely used model, Shannon model, and a
      recently developed model, Scaling ecological diversity model, were theoretically
      analyzed in this paper. It was indicated that Shannon model had many limitations,
      e. g., it could be available only when the number of each type of investigation
      object was more than 100, did not include any information of scale, and could not
      express the richness of diversity. In other words, Shannon model could only
      express the evenness of diversity. A case-study in Fukang of Xinjiang Uygur
      Autonomous Region showed that the richness and Shannon evenness were always
      resolution-dependent, while the ecotope diversity calculated by Scaling
      ecological diversity model was resolution-independent when the spatial resolution
      ranged from 30 m x 30 m to 150 m x 150 m, and strictly increased when the spatial
      resolution ranged from 150 m x 150 m to 480 m x 480 m.

PMID- 16883818
TI  - [Temporal-spatial characteristics of land use in Xinjian County, Jiangxi
      Province].
AB  - With the support of RS and GIS, and using a series of indices in characterizing
      the dynamics of land use, this paper studied the temporal-spatial characteristics
      of land use in Xinjian County, Jiangxi Province, between 1991 and 2000. The
      results indicated that among single land use types, the area for construction
      changed mostly. The annual change speed of comprehensive land dynamic index
      between 1991 and 1995 was 0.5 times higher than that between 1996 and 2000, and
      the utilization grade in 1991, 1996 and 2000 was 243.7, 44.1 and 244.9,
      respectively, being a little higher than the national average grade. The land
      inflow and outflow in 1996 to approximately 2000 was lower than that in 1991 to
      approximately 1995, and the land use change was from bilateral dynamics to
      unilateral unbalanced dynamics.

PMID- 16883819
TI  - [Ecosystem services value of coastal tidal zone in Dongtai City of Jiangsu
      Province].
AB  - The study with satellite remote sensing technique and Costanza method showed that
      from 1984 to 2003, the total area of various ecosystems in the coastal tidal zone
      of Dongtai City, Jiangsu Province increased from 108.54 to 171.31 km2 or by
      57.83% due to natural siltation, of which,the area of natural ecosystem decreased
      from 60. 82 to 21.64 km2 or by 64.42%, while that of artificial ecosystem
      increased from 47.72 to 195.23 km2 or by 309.12%. During the same period, the
      total value of ecosystem services in this zone increased by 76.96%, with natural
      ecosystem services value dropped from 56.26 x 10(4) to 17.19 x 10(4) US dollar or
      by 69.45%, while artificial ecosystem services value raised from 40.55 x 10(4) to
      154.13 x 10(4) US dollar or by 280.10%. The decrease of natural ecosystem area
      and the increase of artificial ecosystem area illustrated clearly that the costal
      tidal ecosystem of this city was being degenerated seriously, and the decline of
      natural ecosystem services value was resulted from this degradation and the
      decrease of natural ecosystem area.

PMID- 16883820
TI  - [Temporal and spatial distribution characteristics and indicator effects of
      Corbicula fluminea in coastal flat of Changjiang estuary].
AB  - Corbicula fluminea is a kind of macrobenthos commonly seen in the coastal wetland
      ecosystem of Changjiang estuary. This paper studied the temporal and spatial
      distribution characteristics of its population density and biomass, and analyzed
      the heavy metals concentrations in its body and in suspended particles and
      sediments. The results showed that the distribution of C. fluminea was discrepant
      in different seasons, sampling sites, and even, sampling sections of same
      sampling site. The population density and biomass of C. fluminea were higher in
      spring and autumn but lower in summer, and higher in mid-tidal flat than in low
      and high flats of Chongming. Its annual average population density and biomass
      was the maximal in Xupu. C. fluminea had definite accumulation ability to copper
      and zinc, but not to lead and chromium. There was a significant negative
      correlation between the lead concentrations in C. fluminea and sediments.

PMID- 16883821
TI  - [Phytoplankton biomass and high frequency of Prorocentrum donghaiense harmful
      algal bloom in Zhoushan sea area in spring].
AB  - Based on the two cruises comprehensive survey on Prorocentrum donghaiense harmful
      algal bloom (HAB) in Zhoushan sea area in spring 2002 and 2003, this paper
      studied the distribution pattern of phytoplankton biomass and its relationships
      with environmental factors. As to the grid station, the mean Chla concentration
      in surface water layer in spring 2002 was 1.09 +/- 1.63 mg x m(-3), ranged from
      0.25 to 9.08 mg x m(-3). While in spring 2003, the survey was conducted in the
      sea area with an isobath of 50 m, where the topography changed suddenly and HAB
      happened frequently, the mean Chla of surface water layer was 4.21 +/- 5.33 mg x
      m(-3), ranged from 0.44 to 24.32 mg x m(-1). The maximum phytoplankton biomass
      appeared at the Changjiang Diluted Water frontal zone between 122.5 degrees E and
      123 degrees E, where had ample nutrients and good conditions for light
      penetration in the water column. During the tracking investigation, the Chla
      concentration in surface water layer in spring 2002 and 2003 was 18.45 +/- 11.04
      mg x m(-3) and 12.47 +/- 8.15 mg x m(-3), respectively. By the tracking
      investigation of P. donghaiense HAB, four results were found: a) the optimum
      salinity was between 26 and 30, b) the large scale and long lasted HAB algae was
      limited by P, c) suitable light condition, nutrients enrichment and water column
      stabilization were the three important conditions for HAB, and d) the convergent
      zone in plume front enhanced the gathering of P. donghaiense.

PMID- 16883822
TI  - [Environmental quality of Guangzhou sea area].
AB  - Based on the water quality investigation data from August 2003 to August 2004,
      and by using single water quality parameter model, integrated water quality index
      model and eutrophication assessment model, this paper assessed the environmental
      quality of Guangzhou sea area. The results showed that the key pollutants were
      dissolved inorganic nitrogen (DIN), dissolved inorganic phosphorus, oil, Cu and
      Pb, with their annual average concentrations of 1.87 mg x L(-1), 0.049 mg x L(
      1), 0.107 mg x L(-1), 6.07 microg x L(-1) and 1.43 microg x L(-1), respectively.
      Among the pollutants, DIN was the most important one. Its concentration exceeded
      the fourth standard of sea water quality, and decreased gradually from inner bay
      to outer bay. Under the effects of Pearl River water flow and land-based
      pollutants, most part of Guangzhou sea area was seriously polluted, and the
      annual averages of single parameter pollution index, integrated water quality
      index, and eutrophication index were 2.22, 6.80 and 48.44, respectively, which
      also decreased gradually from inner bay to outer bay, and from nearshore to
      offshore.

PMID- 16883823
TI  - [Consanguinity of sixteen olethreutid moth species in northeast China based on
      RAPD-PCR analysis].
AB  - With RAPD-PCR technique, the phylogenetic tree of 16 olethreutid moth species in
      northeast China was constructed, and their consanguinity was analyzed. The
      results showed that the clustering of 3 Pandemis species,2 Argyrotaenia species
      and 4 Archips species on this phylogenetic tree was coincident with their
      morphological taxology, but that of some other species was not. For example,
      Clepsis rurinana and C. pallidana were not on the same clade, but on the clade
      with Pandemis cinnamomeana and Ptycholoma imitartor, respectively. Genetic
      distance could be an index for genus, and 0.7 was the boundary. The species
      genetic distance from the same genus was less than 0.7, while that from different
      genus was more than 0.7.

PMID- 16883824
TI  - [Effects of transgenic Bt cry1Ab rice on collembolan population in paddy field].
AB  - To assess the potential ecological risk of transgenic Bt rice to non-target soil
      organisms in paddy field, transgenic crylAb rice KMD1 and KMD2 and their parental
      control rice line XS11 were planted in experimental fields, and collembolan
      species and their densities were investigated during grain-filling and post
      harvest stages in 2003 to approximately 2004. By using an arthropod-sucking
      machine, two collembolan species, Entomobrya griseoolivata and Bourletiella
      christianseni, were collected from the leaf litter at soil surface during grain
      filling stage (September,2003), and the population densities of E. griseoolivata
      in KMD1 and KMD2 paddy fields were significantly higher than those in XS11 paddy
      field. With bags contained rice stem-leaf litter and initially placed in the
      paddy field at harvest time (November,2003), four collembolan species, E.
      griseoolivata, B. christianseni, Hypogastrura matura and Isotoma monochaeta, were
      collected during post-harvest stages (April, 2004), and the densities of E.
      griseoolivata and H. matura in KMD1 and KMD2 paddy fields were also significantly
      higher than those in XS11 paddy field. The biomass loss of KMD1 and KMD2 stem
      leaf litter was significantly greater than that of XS11's.

PMID- 16883825
TI  - [Chemical components of Artemisia scoparia volatile oil and its poison activity
      to mosquito].
AB  - The study showed that Artemisia scoparia contained 0.38% of volatile oil, in
      which, a total of 38 chemical components were identified, accounting for 87.53%
      of the substances detected,and 12 kinds of terpenoids compounds were the main
      components, accounting for 45.04% of the total. The oil had a high and rapid
      poison activity on Culex pipiens pallens larva and adult. The LC50 value for the
      larva was 12.5 mg x L(-1) within 2 days, and the mortality of the adult in 24
      hours was 70% and 100% when the dosage was 1 and 10 microg x cm(-2).

PMID- 16883826
TI  - [Effects of insecticides on insect pest-natural enemy community in early rice
      fields].
AB  - This paper studied the effects of triazophos, shachongshuang, abamectin, and Bt +
      imidacloprid on the insect pest-natural enemy community in early rice fields in
      the Yangtze-Huaihe region of Anhui Province. The results showed that all of the
      test insecticides had significant effects in controlling the growth of major
      insect pest populations. The average value of insect pest-natural enemy community
      diversity under effects of triazophos, shachongshuang, abamectin, and Bt +
      imidacloprid was 1.545, 1.562, 1.691 and 1.915, respectively, while that in
      control plot was 1.897. After two weeks of applying insecticides, the plots
      applied with shachongshuang and abamectin had a similar composition of insect
      pest-natural enemy community, but the community composition was significantly
      different between the plots applied with triazophos and Bt + imidacloprid. From
      the viewpoints of community stability and pest control, Bt + imidacloprid had the
      best effect, and shachongshuang and abamectin were better than triazophos.

PMID- 16883827
TI  - [Insect community structure and its dynamics in Chinese prickly ash plantations
      at different altitudes in Yunnan Province].
AB  - With community character indices and principal component analysis, this paper
      studied the variation of insect community composition and structure in Chinese
      prickly ash plantations at four altitudes in Yunnan Province, and analyzed the
      temporal patterns of the variation and its affecting factors. The results showed
      that with the increase of altitude, the species diversity, abundance and evenness
      of the community decreased gradually, while the population number had a certain
      increase. Such a variation was more obvious with time. The factor dominating the
      variation was the gradual change of the species and individuals numbers of
      natural enemy sub-community to those of pest sub-community.

PMID- 16883828
TI  - [Isolation and identification of Bacillus cereus strain Jp-A and its capability
      in phenol degradation].
AB  - In this study, a bacterial strain named as Jp-A was isolated from the activated
      sludge of a steel factory. Through morphological observation,physiological and
      biochemical test, and 16srRNA sequence analysis, the strain was identified as
      Bacillus cereus. Under laboratory condition, the phenol at its initial
      concentration of 5,10 and 15 mmol x L(-1) could be completely degraded by the
      strain within 16,24 and 32 h, respectively, but the growth of the strain was
      inhibited when the phenol concentration was 30 mmol x L(-1). The strain could
      also utilize and degrade other aromatic hydrocarbons, e. g. , benzene, toluene,
      chlorophenol and nitrophenol, as its sole source of carbon and energy.
      Dioxygenase test indicated that the strain degraded phenol via meta-pathways. The
      key enzyme catechol 2,3-dioxygenase was an induced enzyme, which was mainly
      located on the cell membrane, and adding glucose could inhibit its generation.

PMID- 16883829
TI  - [Effects of metolachlor on biological activities in celery rhizophere and non
      rhizosphere soil].
AB  - The study with rhizobag showed that in celery rhizophere and non-rhizosphere
      soil, metolachlor had a certain inhibitory effect on catalase activity, but
      stimulated dehydrogenase activity. Generally, the enzyme activities in
      rhizosphere soil were higher than those in non-rhizosphere soil. After 45 days of
      metolachlor treatment, the numbers of bacteria and fungi in rhizosphere soil were
      higher than those in non-rhizosphere soil, and the R/S was 1.76 to approximately
      2. 51. The numbers of actinomycetes were relatively stable, and the rhizosphere
      effect was not significant. The degradation rate of metolachlor in rhizosphere
      and nonrhizosphere soil was 0. 0217 and 0.0176, and the corresponding half-live
      was 31.9 and 39.4 days, respectively. The degradation of metolachlor was enhanced
      greatly in rhizosphere soil.

PMID- 16883830
TI  - [Farmland ecosystem service and its formation mechanism].
AB  - Farmland ecosystem service has a real and far-reaching effect on the sustainable
      development of human society, and its study is one of the hotspots in ecology.
      This paper introduced the connotations of farmland ecosystem service and its
      valuation methodology, and summarized the present status in researching the
      formation mechanism of farmland ecosystem service from the aspects of the
      characteristics of abiotic environment, biota, ecosystem process, and human
      activity. It's considered that besides its importance in supplying human society
      a great number of products, farmland ecosystem is of significance in providing
      environmental service and maintaining regional ecological safety. Abiotic
      environment, biota, ecosystem process, and their interactions are the bases of
      the formation of farmland ecosystem service, and human activity is the primary
      driving force. It's imperative to build up an indices system to valuate farmland
      ecosystem service, and to strengthen the research of the effects of human
      activity on the farmland ecosystem service formation.

PMID- 16883831
TI  - [Research advances in depth of edge influence of landscape boundary].
AB  - Depth of edge influence of landscape boundary is an important component of
      landscape boundary research, and also, the hotspot of ecological research at home
      and abroad. This paper summarized the recent decades' research advances abroad in
      depth of edge influence, including quantitative methods, depth of edge influence
      on abiotic and biotic factors, and affecting factors on depth of edge influence.
      The studies on depth of edge influence in our country were also discussed,with
      the development trend prospected.

PMID- 16883832
TI  - [Responses of enzymes in terrestrial plants to enhanced UV-B radiation].
AB  - With the destruction of ozone layer, ultraviolet-B (UV-B, 280 to approximately
      320nm) radiation has being enhanced at the earth's surface. The energy of UV-B
      irradiation is far higher than that of visible light, which could be absorbed by
      biomacromolecules such as protein and nuclei acid. Enzyme is a sort of protein
      catalyzing the biochemical processes, and its content and activity in plant have
      strong responses to enhanced UV-B radiation. This paper summarized the research
      advances in the effects of enhanced UV-B radiation on the key enzymes, mainly
      including antioxidant enzymes, ribulose-1, 5-diphosphoscarboxylase, nitrate
      reductase and glutamine synthetase in terrestrial plants. Some suggestions for
      future research in this field were put forward.

PMID- 16883833
TI  - [Changes of nutrients in soil of transgenic Bt crops].
AB  - Pot experiment showed that after 30 days of transgenic Bt rice planting and by
      the end of the growth season of transgenic Bt cotton, the contents of soil total
      C, total N, alkali-hydrolyzable N, and available P and S had no significant
      difference with the control, which suggested that there was a little disturbance
      in the cycle and balance of soil nutrients after a short period of transgenic Bt
      crops planting.

PMID- 16883834
TI  - [Changes of species diversity in gap gradient of mid-subtropical evergreen broad
      leaved forest in Wanmulin Forest].
AB  - Based on the investigation of gap and non-gap stands in the mid-subtropical
      evergreen broad-leaved forest in Wanmulin Nature Reserve of Fujian Province, this
      paper studied the changes of species diversity in gap gradient and in gaps with
      different sizes. The results showed that the species richness and diversity
      decreased gradually from gap center to non-gap, ecological dominance was higher
      in center and lower in edges, and species evenness was in adverse to ecological
      dominance. The species diversity in all areas of gap was the maximum when the gap
      size was 200 to approximately 300 m2.

PMID- 16883835
TI  - [Effects of habitat patch on Lophura nycthemera population].
AB  - To understand the relationships between the distribution of Lophura nycthemera
      population and the attributes of habitat patch,this paper investigated the
      population of L. nycthemera in the National Gutian Mountain Natural Reserve and
      its periphery area in Zhejiang Province from September 1998 to August 1999. The
      relative population density of L. nycthemera in each patch was determined by
      transect census with collecting molted feathers, and the effects of vegetation
      and landscape characteristics on the relative population density and patch
      occupancy were analyzed by statistic methods. The results showed that the
      occurrence of L. nycthemera was significantly affected by patch area,total
      cover,arbor cover,and shrub height. High frequency occurrence of L. nycthemera
      was observed in the patches with large area, dense total cover, dense arbor cover
      and high shrub height, and high relative population density was found in large
      size patches. There was a significant positive linear correlation between
      relative population density and patch area.

PMID- 16883836
TI  - [A measurement of optical emission from the rear surface with solid targets
      irradiated by ultrashort pulse laser].
AB  - The integrated image spectrum and scattering light spectrum of optical emission
      at normal direction from rear-side of a metallic foil were measured, employing
      optical CCD camera and OMA optical multi-channel spectrometer. The integrated
      image spectrum shows that it presents a ring-shape, and in the near margin of the
      ring-shape a bright localized signal is shown, which is optical transition
      radiation (OTR) generated by hot electrons transport through solid targets. The
      scattering spectrum shows that it presents a series of nonperiodic sharp spikes
      between 300-500 nm, and the sharp spike is ascribed to the coherent transition
      radiation (CTR) generated by bunches of hot electron beams generated in v x B
      acceleration mechanism near 400 nm (2 omega). The intensity of transition
      radiation decreases with the increase of the target thickness.

PMID- 16883837
TI  - [Optical and morphological investigation on the interaction of dual dopants in
      poly (N-vinylcarzole)].
AB  - The effect of optical and electrical properties of poly(N-vinylcarzole) (PVK)
      doped with two dyes, i. e. 8-tris-hydroxyquinoline (Alq3) and 4
      (dicyanomethylene)-2-tert-butyl-6 (1, 1, 7, 7-tetramethyljulolidyl-9-enyl)-4H
      pyran (DCJTB), on the energy transfer and charge trapping processes was
      investigated. The phase separation in blends film at different doping
      concentration was also studied. More homogeneous dispersion of dyes in PVK with
      increasing doping concentration was showed. The results indicate that there is a
      certain interaction of Alq3 and DCJTB in this dual-doped system. It is the
      incorporation of DCJTB that untangled the aggregation of Alq3 owing to the
      interaction of DCJTB and Alq3. But for higher doping concentration, DCJTB results
      in an isolated charge transport channel that decreases the electroluminescence
      (EL) operating voltage.

PMID- 16883838
TI  - [Study on the nonlinear Raman lidar monitoring the CO2 gas].
AB  - It is a new skill to use SRS rays as emitting waves for the lidar monitoring CO2
      gas, and the nonlinear Raman lidar based on the SRS process was devised. The
      third harmonic Nd: YAG laser wave (354.7 nm) was injected into the Raman cells
      filled with higher pressure gases, CO2 and N2. The first Stokes (S1) line 371.66
      nm (CO2) and 386.7 nm (N2) were generated by stimulated Raman scattering. The
      variable S1 energy was measured by changing the gas pressure in the Raman cell
      andthe Nd:YAG laser system output energy. The optimum pressures of the CO2 and N2
      in the Raman cell were achieved. Moreover, the principles of this physical
      process were put forward. This skill has been applied to the lidar for monitoring
      the CO2 gas.

PMID- 16883839
TI  - [Enhancement effect of argon atmosphere at high pressure on radiation intensity
      of laser-induced soil plasmas].
AB  - In the present paper, the effects of argon atmosphere at high pressure (0. 2-1.1
      MPa) on the radiation intensity of the plasma induced by a high energy neodymium
      glass laser (energy -30 J, pulse width 0.7 ms) were studied by recording the
      photograph and spectra of the plasma as well as measuring the ablated mass. The
      experimental results show that the volume of the plasma was compressed, the
      temperature increased, and the lightness enhanced significantly when pressure was
      raised. Under our experimental condition, the radiation intensities of the
      plasmas were enhanced with the increase in the gas pressure; but the ablated mass
      of the sample decreased. The measured results are discussed, combined with the
      process of the experiment.

PMID- 16883840
TI  - [Measurement of molecular vibrational temperature in dielectric barrier discharge
      in argon/air at atmospheric pressure].
AB  - Vibrational temperature of N2 (C 3IIu) molecules in dielectric barrier discharge
      (DBD) in argon/air at atmospheric pressure, in which the water electrodes were
      employed, was measured by using a method of spectrum diagnosis. Emission spectral
      lines of the N2 second positive band system(C 3IIu --> B 3IIg) and the sequences
      of vibrational bands with deltav = -1, deltav = -2 and deltav = -3 were used in
      the calculation. The experiment results show that the molecular vibrational
      temperature of N2 is in the range from 1 938 K to 2 720 K, and it increases
      almost linearly with increasing the air content in gas mixture. These results are
      of great importance to the study of plasma dynamics of DBD.

PMID- 16883841
TI  - [Structure and luminescence properties of Eu3+ complexes with benzoic acid and
      1,10-phenanthroline incorporated in SiO2, SiO2-B2O3 and SiO2-B2O3-Na2O matrices].
AB  - Eu3+ Complexes with benzoic acid and 1,10-phenanthroline incorporated in SiO2,
      SiO2-B2O3 and SiO2-B2O3-Na2O matrices were prepared via the sol-gel method. Eu
      doped SiO2, SiO2-B2O3 and SiO2-B2O3-Na2O luminescence materials were synthesized.
      The luminescence of Eu3+ was studied with excitation spectra and emission
      spectra. Different forms of dopants could influence the luminescence properties.
      The structure of Eu-doped glass was studied by comparing IR, TEM and XRD. The
      results showed that after the materials were annealed at 1 000 degrees C the
      structure was very stable because ingredient was already removed totally. The
      emission spectrum showed that the typical optical spectrum of Eu3+ is 5D0 --> 7Fj
      (j = 1, 2) at 588 nm and 614 nm. Comparing EuCl3 with Eu3+ complexes with benzoic
      acid and 1,10-phenanthroline as dopant, the latter has strong luminescence
      property though it has small mass fraction. The luminescence intensity of Eu(3+)
      doped SiO2-B2O3 glass material was weaker than that of Eu(3+)-doped SiO2 glass
      material, and the former's spectrum showed that there were Si-O-B bonds. The
      luminescence intensity of Eu3+ was quenched by this kind of structure. The
      luminescence intensity of Eu(3+)-doped SiO2-B2O3-Na2O glass material was greatly
      increased, and the infrared spectrum illustrated that there was not vibration
      absorption of Si-O-B bonds. Probably Na replaced B, and Si-O-Na bonds formed.
      This kind of structure could enhance luminescence intensity of Eu3+ to some
      extend.

PMID- 16883842
TI  - [Luminescence properties of Ba2MgSi2O7 : RE].
AB  - In the present paper, alkaline earth silicates Ba2MgSi2O7 : RE were prepared
      under a reducing atmosphere by solid-state reaction. Under UV light excitation,
      Ce3+ doped pyrosilicates phosphors emit efficient bluish violet light. The
      emission spectra of Eu2+ doped pyrosilicates phosphors showed that Eu2+ ions
      could occupy two types of sites in Ba2MgSi2O7 host. The energy transfer from Ce2+
      to Eu2+ in Ba2MgSi2O7 is efficient, as there is a large overlap between Ce3+
      emission bands and Eu2+ excitation bands. Analysis of the spectra of Ce3+ and
      Tb3+ co-doped phosphor indicated the existence of energy transfer from Ce3+ to
      Tb3+ in Ba2MgSi2O7 under UV excitation.

PMID- 16883843
TI  - [The emission mechanisms of two kinds of Tb complexes doped in PVK system].
AB  - Two kinds of new rare earth complexes Tb(p-MBA)3phen (sample I) and Tb(p-ClBA)3
      phen (sample II) were synthesized, and photoluminescence (PL) and
      electroluminescence (EL) characteristics of the terbium complex and PVK blended
      system were investigated. As to the sample I , the emission of PVK was completely
      restrained in the EL spectra of the blended film; while in the PL spectra,
      obvious emission of PVK appeared besides the emission of Tb3+. But as to the
      sample II, only the green emission from Tb3+ can be observed in both PL and EL
      spectra of the doping system. So there are two processes that occur in sample I,
      one is the incomplete Forster energy transfer process from PVK to the Tb complex,
      and the other is the car rier charge trapping process. The main mechanism of
      sample II is the energy transfer process.

PMID- 16883844
TI  - [Recent progress in flow-injection chemiluminescence for pharmaceutical
      analysis].
AB  - Flow-injection chemiluminescence(FI-CL) analysis has made great progress in
      analytical chemistry for its high sensitivity with a wide linear range, simple
      instruments, rapidity and reproducibility in signal detection, and being
      appropriate for on-line analysis. A review with 74 references dating from 2002
      early 2004 is given of the application of FI-CL method in the determination of
      drugs.

PMID- 16883845
TI  - [Depth profiles of high-density polyethylenes filled with different inorganic
      fillers during natural photo-oxidation by infrared microscopy].
AB  - The natural photo-oxidation degradation of HDPE filled with different inorganic
      fillers was carried out, and the depth profiles of the standard samples were
      characterized by infrared microscopy (IM) and scanning electron spectroscopy
      (SEM). The results show that HDPE filled with different inorganic fillers show
      different depth profiles. For HDPE and CaCO3-filled HDPE, there are no cracks on
      the cross sections, and the carbonyl indexes remain nearly zero from the surface
      to the interior. For HDPE filled with black mica, mica, kaolin and diatomite,
      there are more or less parallel, comb-like cracks on the cross sections, and the
      carbonyl indexes show decreasing trends from the surface to the interior.
      Furthermore, the transition points in CI curves are basically consistent with the
      formation of cracks in these samples. The UV absorbances of these inorganic
      fillers demonstrate the relationship between the photo-oxidation of HDPE and the
      relative absorbances of inorganic fillers. This implies that the UV absorbance of
      the inorganic filler may be responsible for the occurrence of cracks and
      oxidation in the standard samples.

PMID- 16883846
TI  - [FTIR investigation of organic phase containing rare earth ion in naphthenic acid
      phosphonate ester-heptane system].
AB  - Naphthenic acid (NA) was mixed with PC88A in heptane, and 10 moL x L(-1) KOH
      aqueous solution was used to saponify the solution subsequently. The transparent
      and clear appearance of the obtained solution indicated the formation of w/o
      micell and microemusion. In the present study, micell with high saponification
      percentage (80%) was used to extract neodymium. The organic phase structure was
      characterized using FTIR spectroscopy in the extraction process. IR spectra
      indicate that the characteristic peaks of nu(COOH), nu(s)(COO-) and nu(P=O) shift
      to lower wavenumbers as the loading of Nd in organic phase increases. The results
      demonstrated that Nd(III) are coordinated to P=O and COO- groups simultaneously,
      and the supramolecules with self-assembly structure was formed containing PC88A
      and NA, which were binding with Nd(III) in the extracted organic phase.

PMID- 16883847
TI  - [Monitoring cerebral oxygenation using near infrared spectroscopy during
      cardiopulmonary bypass surgery].
AB  - To avoid cerebral hypoxia caused by the imbalance between cerebral oxygen supply
      and consumption, regional cerebral oxygenation of patients need to be monitored
      at real time during cardiopulmonary bypass (CPB) surgery, and the physiological
      parameters can be regulated and emergent treatment can be used according to it.
      Using the near infrared (NIR) instrument developed by our group, cerebral
      oxygenation of the patients under cardiac surgery was monitored. The instrument
      consists of a two-wavelength near infrared light source and two near infrared
      detectors. Hemoglobin concentration changes of regional cerebral tissue were
      calculated, and by steady-state spatially resolved spectroscopy (SRS) algorithm,
      regional cerebral oxygen saturation (rSO2) was also calculated. Physiological
      parameters of patients, such as mixed venous oxygen saturation (SvO2), were
      measured by another monitor during CPB. Hemoglobin concentration changes were
      easily disturbed, but the anti-disturbance ability of rSO2 was good. The value of
      rSO2 could be detected all over the surgeries, but SvO2 could be detected only
      during CPB. There were positive correlations between rSO2 and SvO2 in most of the
      patients, but the correlation coefficients were not very high. This was because
      SvO2 reflects the saturation of the main venous, but rSO2 reflects regional
      cerebral oxygenation. So the physiological meaning of rSO2 and SvO2 is different.
      The results indicate that cerebral oxygenation of patients can be reflected by
      rSO2 during CPB, while only monitoring SvO2 is not enough.

PMID- 16883848
TI  - [The PLS calibration model optimization and determination of rice protein content
      by near-infrared reflectance spectroscopy].
AB  - A hundred and ninety one representative brown rice samples from the Chinese Rice
      Genebank and the DH population derived from the cross of japonica upland rice
      IRAT109 with paddy rice Yuefu were selected for this study. Their protein content
      range was 5.90%-14.50%. Near-infrared diffusive spectroscopy (NIDRS) and partial
      least square (PLS) were used to determine protein content with different
      wavelength ranges and data preprocessing methods for regression and information
      extraction. The object function [R/(1+RMSECV)] of quantitative model was defined,
      and the samples of calibration and validation tests were classified by projective
      distribution of PLS loadings. These methods were applied to the optimization of
      the calibration model. It is demonstrated that the calibration model developed by
      the spectral data pretreatment of the first derivative + standard vector
      normalization with the same spectral region (5 000-9 000 cm(-1) resulted in the
      best determination of protein content in brown rice when the maximum values of
      the object function were reached. The maximum values of the object functions of
      calibration and validation sets were 0.701 and 0.687, respectively. Projective
      distributions of PLS loadings were used to validate the models, and the result
      was the same as that of validating model by object function [R/(1+RMSECV)].

PMID- 16883849
TI  - [Temperature effect on the noninvasive measurement of human blood glucose by
      NIR].
AB  - During the noninvasive measurements of body blood glucose, the result will be
      effected by many factors, such as the measuring conditions including temperature,
      contact pressure and so on, and in addition the change of body's state also will
      induce some error. However, among so many factors the temperature is very
      important and should be discussed. To find the quantitative value of the result
      bias caused by temperature in the wavelength range from 1 100 to 1 700 nm, the
      aqueous glucose with the concentration ranging from 10 mg x dL(-1) to 200 mg x
      dL(-1) and 10 mg x dL(-1) interval was detected at temperature of 15, 20, 25, 30,
      35 and 40 degrees C. Then six different models at different temperature were
      founded and predicted one another. The maximum RMSEP result of models is 11. 227
      9 mg x dL(-1) and the minimum is 3. 298 8 mg x dL(-1). The correlation is about
      0.98. The authors have also found that 1 degrees C change of temperature will
      induce deltac = 2.662 (mg x dL(-1) x degrees C(-1)) change of the prediction
      result, so these show that the detect error will be minimal when the temperature
      of measuring is the same as that of modeling. Moreover, the authors put forward
      two approaches to decreasing or compensating the error induced by the
      temperature.

PMID- 16883850
TI  - [The effects of noise on NIR analysis and related mathematic pretreatments and
      models].
AB  - The feasibility of using a relatively high noise NIR spectrometer for analysis
      was examined by using maize powder samples. The results showed that with four
      time averaged NIR spectrum data without more pretreatments, PLS mathematic models
      and CAU-NIR software, the relative high noise scan NIR spectrometer could be used
      to get satisfied prediction results compared with other low noise NIR
      spectrometers. The prediction coefficient could reach 98% and the CV (variation
      coefficient) was 6.2%. It was proved that when the S/N of NIR spectrometer was
      lower than 10(5), it still could be used for quantity analysis with the help of
      some mathematic pretreatments and models.

PMID- 16883851
TI  - [A study of preparation and infrared absorbency of La2O3 nanocrystals].
AB  - Nanocrystals were prepared by stearic acid gel method. The structure and
      morphology of nanocrystals were characterized by X-ray powder diffraction (XRD),
      transmission electron microscope (TEM) and infrared spectra. Experimental results
      show that the absorption peaks of La2O3 extendwith their blue shift or red shift.
      The absorption of La2O3 nanocrystals is good in the wavelength range of 1 000 to
      1 700 nm, where La2O3 nanocrystals may serve as a kind of absorbent of laser
      camouflage material.

PMID- 16883852
TI  - [Discrimination of varieties of apple using near infrared spectra based on
      principal component analysis and artificial neural network model].
AB  - A new method for the discrimination of varieties of apple by means of near
      infrared spectroscopy (NIRS) was developed. First, principal component analysis
      (PCA) was used to compress thousands of spectral data into several variables and
      describe the body of spectra, the analysis suggested that the cumulate
      reliabilities of PC1 and PC2 (the first two principle components) were more than
      98%, and the 2-dimentional plot was drawn with the scores of PC1 and PC2. It
      appeared to provide the best clustering of the varieties of apple. The loading
      plot was drawn with PC1 and PC2 through the whole wavelength region. The
      fingerprint spectra, which were sensitive to the variety of apple, were obtained
      from the loading plot. The fingerprint spectra were applied as ANN-BP inputs.
      Seventy five samples from three varieties were selected randomly, then they were
      used to build discrimination model. This model was used to predict the varieties
      of 15 unknown samples; the distinguishing rate of 100% was achieved. This model
      is reliable and practicable. So the present paper could offer a new approach to
      the fast discrimination of varieties of apple.

PMID- 16883853
TI  - [Study on vibrational spectra and structure of 4-mercaptopyridine monomer and
      dimer using density functional theory].
AB  - The optimized molecular structure and vibrational frequencies of 4
      mercaptopyridine monomer and dimer were studied by density functional theory
      using B3LYP method with the 6-311++G(d, p) basis set. On the basis of the
      calculations, the assignments of vibrational spectra were performed on monomer
      and dimer, and the change in structure and vibrational spectrum of dimer as well
      as the intermolecular force of forming dimer were investigated. It was found that
      the two pyridine ring planes are vertical to each other, and the dimer was formed
      through H-bonding, which is between the nitrogen on one ring and the hydrogen of
      SH moieties on another. Furthermore, the structure and vibrational spectrum of
      the dimer have some changes with respect to those of the monomer.

PMID- 16883854
TI  - [Surface enhanced Raman scattering spectra of phytic acid in the sol silver
      oxide].
AB  - Surface enhanced Raman scattering spectra of phytic acid were recorded in the sol
      oxide silver. Based on ab-initio/ STO-3 quantum calculations results, assignments
      to the vibrational modes of phytic acid were carried out. On the basis of the
      mechanism of SERS, the adsorption modes were suggested that phytic acid
      chemically adsorbed on the oxide silver surface through four phosphate bonds.

PMID- 16883855
TI  - [Raman scattering spectra of Ca3NbGa3Si2O14 (CNGS) crystals].
AB  - The CNGS crystal belongs to the trigonal system, the 32 point group and the P321
      space group, which is the same as the LGS crystal. Its lattice constants are a =
      0.808 73 nm and c = 0.497 98 nm. The primitive cell of the CNGS crystal contains
      only one formula unit (23 atoms). The vibration modes were measured with Raman
      spectroscopy technique, assigned with ab initio molecular orbit calculation
      method. In order to model the crystal, two clusters Ca3NbGa2SiO12 and
      Ca3NbGaSi2O12 were designed, and calculations were carried out on them. Their
      configurations were optimized, and the vibration frequencies were calculated with
      UHF method. By investigating the force constants and activities of the assigned
      Raman spectra, the structure of CNGS crystal was analyzed, and its layer
      structure and piezoelectric properties were confirmed. It is concluded that CNGS
      crystals have more excellent anisotropy and piezoelectric properties than LGS
      crystals.

PMID- 16883856
TI  - [Influence of different light source on the laser Raman spectra in determination
      of sodium glutamic acid].
AB  - The influences of different laser source and different light power on laser Raman
      spectra were studied for the sodium glutamic acid. The results show that some
      influences existed using different wavelength and power of light source the peak
      shifting 6 cm(-1). As UV laser has great light power, the samples were destroyed,
      making the Raman spectra- reduce or disappear. The attenuation of light was
      needed. The linear relation existed between the Raman intensity and the power of
      laser light source, and the correlation coefficient was more then 0.999. The
      Raman intensity per light power unit was related to the wavelength, and was not
      related to the power of laser source.

PMID- 16883857
TI  - [Confocal Raman microspectroscopic study of human breast morphological elements].
AB  - Breast tissue sections were examined by means of confocal Raman spectroscopy with
      an excitation wavelength of 633 nm. Acquired using a microscopic mapping approach
      with the sample volume of -2 microm3, these spectra were compared with the ones
      of the commercially available actin, DNA, collagen (type I), triolein etc. Some
      spectra were distinguished and identified and characterize the morphological
      elements like cell cytoplasm, extracellular matrix etc. The cell nucleus spectrum
      was also obtained by K-means cluster analysis. The correlation analysis showed
      that the spectrum from a morphological element is highly correlated with that
      from the corresponding purified chemical. The spectroscopic characterization of
      these morphological elements was then investigated. This study is helpful to
      understanding the chemical/morphological basis of the Raman spectrum and
      designing the Raman microspectroscopic model of human breast tissue.

PMID- 16883858
TI  - [SEM, XRD and FTIR investigation on crystal growth of calcium oxalate modulated
      by sodium tartrate].
AB  - Crystallization of calcium oxalate (CaOxa) was investigated in the presence of
      sodium tartrate (Na2 tart) of different concentration in a gel system by scanning
      electron microscopy (SEM), X-ray diffraction (XRD) and Fourier transform infrared
      (FTIR) spectroscopy. It was found that in the presence of a low concentration of
      Na2tart (0.01 mol x L(-1)), calcium oxalate monohydrate (COM) is the dominant
      crystal phase. The percentage of calcium oxalate dihydrate (COD) is less than 5%.
      In the XRD pattern the main diffraction peaks are (101), (020), and (202) planes
      of COM crystals. In the FTIR spectrum, the main asymmetric carbonyl stretching
      band nu(as) (COO-) and the metal-carboxylate stretch nu(s) (COO-) of COM occur at
      1 618 and 1 317 cm(-1), respectively. With the concentration of Na2 tart
      increasing to 0. 10 and 0. 50 mol x L(-1), the percentage of COD crystals
      increases to 10% and 50%, respectively, and the surface area of COM crystals
      decreases. The diffraction peaks that assigned to the (200), (211), (411), and
      (213) planes of COD crystals become stronger and stronger. The temperature can
      influence the modulation of Na2 tart in terms of the phase composition and
      morphology of CaOxa crystals. As the temperature decreases, the percentage of COD
      increases. At a higher temperature beyond 47 degrees C, COM is the dominant
      phase; but COM is dominant when the temperature is lower than 27 degrees C. The
      nu(as) (COO-) and nu(s), (COO-) of COD crystals occur at 1 647.6 and 1 327.7 cm(
      1), respectively.

PMID- 16883859
TI  - [Study on structures of blattela germanica allergen, Bla g 2 expressed by
      eukaryotic and prokaryotic vectors using fluorescence and CD spectra].
AB  - The recombinant allergen, Bla g 2, was expressed by prokaryotic vector E. coli
      and eukaryotic vector P. Pastoris. The different structures and configurations of
      the Bla g 2 from E. coli and P. Pastoris were studied by fluorescence and
      circular dichroism. The secondary structures of Bla g 2 in solution, and the
      composition besides the type of its tertiary structure were proposed. These
      studies help understand the differences between prokaryotic and eukaryotic
      expression systems, reveal the relationship between the structure and the
      function of Bla g 2, and improve the production of this significant allergen.

PMID- 16883860
TI  - [Study of red tide spectral characteristics and its mechanism].
AB  - In situ spectral data of different red tide, whose dominant species are
      leptocylindrus danicus, chattonella marina, skeletonema costatum, and mesodinium
      rubrum, were acquired by above water method utilizing spectrometer manufactured
      by FieldSpec Dual VNIR (USA). It is emphasized that the characteristic
      reflectance peak lying between 687 and 728 nm can be used to distinguish between
      red tide and normal sea water. Also the spectral discrepancy between different
      dominant species of red tide is pointed out, which could be utilized to identify
      certain red tide species by remote sensing technique. Mechanisms of phytoplankton
      red tide spectra peaks and vales are given. Spectral characteristics of
      mesodinium rubrum, a kind of protozoan, may be related to its symbiotic alga in
      its body and phytoplankton pigment crumb. So, research on ingestion preference,
      symbiotic property with algae, and fluorescence emission character of such
      symbiotic algae under normal temperature may be helpful for the deep
      understanding of mechanism of mesodinium rubrum spectra.

PMID- 16883861
TI  - [New method and instrument to diagnose crop growth status in greenhouse based on
      spectroscopy].
AB  - Spectral reflectance of cucumber leaves in greenhouse was measured using an ASD
      FieldSpec Pro VNIR spectrometer with natural illumination. Two sensitive
      wavelengths, 527 nm and 762 nm, were selected to evaluate the nitrogen content of
      the cucumber leaves. A model was established and validated using normal
      difference color index(NDCI) with the correlation coefficient of 0.881. Based on
      the above efforts, a handheld spectral instrument was developed to diagnose the
      growth status of the crop in greenhouse using fiber optics. The instrument was
      mainly composed of four parts: reflected light acquisition system, light
      intensity measurement unit, signal conditioning unit, and data acquisition
      system. The sunlight reflected by the crop was transmitted by the fiber, and
      passed through the light filter to obtain light at the sensitive wavelengths.
      Finally it was transformed into electronic signal by the photoelectric
      transistor, and was used to diagnose the growth status of the crop according to
      the evaluation model. The result showed that the developed instrument was
      practical.

PMID- 16883862
TI  - [Preparation of adsorbent made from sewage sludge and its spectrum properties].
AB  - Biochemical sludges of sewage and petrochemistry and surplus sludge were taken as
      raw materials to prepare adsorbents for flue gas desulfurization by pyrolysis. To
      compare with active carbon, the abilities of adsorbents made from different
      sludges were studied by SEM, X-ray diffraction diagram, TG and DTA, pore
      characteristics and elements analysis, and the adsorption mechanisms of systems
      of SO2 -O2-N2 and SO2-O2-H2O(g)-N2 were studied by FTIR. Results indicated that
      the desulfurization performance of adsorbent made from surplus sludge was better,
      subsequent was petrochemical sludge, and the adsorbent made from biochemical
      sludge of sewage was worse. The desulfurization efficiency of adsorbent made from
      surplus sludge was slightly lower than active carbon. In the system of SO2-O2-N2,
      physical adsorption was primary, but in the condition of water, chemical
      adsorption was primary, where catalysis and oxidation of SO2 took place in sludge
      derived adsorbent. In adsorption process, the adsorption depends on micropore
      structure.

PMID- 16883864
TI  - [Nonlinear Kalman filter simultaneous determination of mixture of phenol and 2
      chlorophenol].
AB  - An analysis method of nonlinear absorbance for binary composition mixture was
      proposed. The nonlinear absorbance was composed of the contributions from both
      themselves and the change in their contributions due to mixing, as well as the
      contribution from their interaction. The mixture of phenol and 2-chlorophenol was
      simultaneously determined using nonlinear Kalman filter UV spectrophotometry. UV
      absorption spectra were obtained with 32 standard solutions (range 1-15 mg x L(
      1)) and 71 wavelengths(250-290 nm). Standard work matrix of extended Kalman
      filter was performed from partial least-squares method. The vectors function
      Jacobi matrix was obtained by linearization of Taylor series for nonlinear
      absorbance formula. The recovery experiment showed that the extended Kalman
      filter simultaneous determination of mixture of phenol and 2-chlorophenol that is
      not only exact, but also stable.

PMID- 16883863
TI  - [Spectroscopy study of the immobilized cellulase of magnetic nanoparticles
      Fe3O4].
AB  - Fe3O4 magnetic nanoparticles were synthesized by chemical coprecipitation method
      using ammonia as the precipitator in the present paper. And then cellulase was
      immobilized on Fe3O4 magnetic nanoparticles via carbodiimide activation, which
      was testified by FTIR and lots of repeating catalysis experiments. The morphology
      of nanoparticles immobilized by cellulase was characterized by TEM, and the
      activity of cellulase was measured by DNS spectrophotometry. The optimum
      temperature (60 degrees C) and pH value (3.94-5.50) for the catalysis ablility of
      immobilized cellulose were studied. The result showed that compared with the
      native enzyme the cellulase immobilized on Fe3O4 magnetic nanoparticles has the
      advantages of thermal stability, storage stability, and more extensive optimum pH
      value.

PMID- 16883865
TI  - [Study on the method of rapid quality control of aqueous solution of flos
      lonicerae japonicae extraction in the preparation of qingkailing injection].
AB  - To establish a rapid and accurate on-line quality control method for aqueous
      solution of Flos Lonicerae Japonicae extraction (ASFLJE) in the preparation of
      Qingkailing injection, the wavelength of UV original spectrum and its first
      derivative spectrum of ASFLJE were scanned. The most suitable spectrum type and
      wavelength correlated with the chlorogenic acid content in ASFLJE determined by
      RP-HPLC were chosen to build a regress model. The UV equation for predicting
      chlorogenic acid content in ASFLJE was established. Other 10 batches of ASFLJE
      were used for testing the on-line prediction results by comparison of the values
      of chlorogenic acid content determined by HPLC and predicting equation
      respectively. The most suitable wavelengths correlated with chlorogenic acid
      content were 294 nm (r = 0.991 9, n = 28) in the original UV spectrum and 316 nm
      (r = 0.995 9, n = 28) in the first derivative spectrum respectively. The
      predicting equation of chlorogenic acid content was: c(mg x mL(-1)) = 506. 254 3
      x A316 nm + 0.177 1 (r = 0.995 9, n = 28). This predicting equation is credible
      and accurate, as tested by HPLC method (r = 0.991 5, n = 10). The prediction
      results of chlorogenic acid content were: the chlorogenic acid content in
      probable 90 percent ASFLJE was: 0.4-4.0(mg x mL(-1)). This method is rapid,
      simple and accurate, and can be used for the on-line quality control of ASFLJE in
      Qingkailing injection preparation.

PMID- 16883866
TI  - [Library search of UV spectra of organic environmental pollutants based on neural
      network].
AB  - The effects of optimization of network parameters, noise, and impurity on the
      network were investigated detailedly. To speed up the convergence of the network
      and enhance the resolution of the library search of UV spectra, the derivative
      spectra for BP-ANN library search was proposed. The method has a higher tolerance
      to noise and impurity levels than using ordinary UV spectra, especially to slop
      background levels. Finally, the resolutions of library search of UV spectra with
      ANN with optimized parameters were compared with conventional correlation
      coefficient method. Results showed that the ANN is superior to conventional
      correlation coefficient method and is an effective method for library search of
      UV spectra.

PMID- 16883867
TI  - [Spectrophotometric determination of azithromycin by charge transfer reaction].
AB  - The charge transfer interactions of Azithromycin and 7,7,8,8
      tetracyanoquinodimethane (TCNQ) or chloranilic acid (CL) were investigated by
      spectrophotometry. The apparent molar absorptivity of TCNQ complex is 2.7 x 10(4)
      L x mol(-1) x cm(-1) at 743 nm, and 5.0 x 10(4) L x mol(-1) x cm(-1) at 842 nm;
      and that of CL complex is 2.4 x 10(3) L x mol(-1) x cm(-1). Beers law is obeyed
      in the concentration range of 0-30 mg x L(-1) for TCNQ method, and 5-225 mg x L(
      1) for CL method. The relative standard deviations of the two methods are 1.0%
      and 1.4% (n = 6), respectively. The composition of complex of Azithromycin with
      7,7,8,8-tetracyanoquinodimethane or chloranilic acid is 1 : 2. This proposed
      method has been applied to the determination of Azithromycin in tablets with
      satisfactory results.

PMID- 16883868
TI  - [ICCD-based fast fluorescence micro-imaging technique and preliminary application
      in living cells].
AB  - A fast fluorescence micro-imaging system using mainly intensified charge couple
      device (ICCD), argon-ion laser, and xenon lamp was set up, and its preliminary
      application in living cells was presented. Real-time observation and imaging of
      fast concentration and distribution changing of intracellular Ca2+ labeled by
      Fluo-3, a fluorescent Ca2+ indicator, in the proliferation process of rat
      cerebral micro-vessels endothelial cells (rCMECs) were carried out, and curves of
      artificial intensity versus imaging sequence of four typical points were
      obtained. It is shown that the ICCD-based fast fluorescence micro-imaging system
      is a powerful tool for recording the real-time fast processes in living cells.

PMID- 16883870
TI  - [Self-absorption of NO fluorescence induced by two-photon].
AB  - The two-photon LIDFS of NO excited with 452.4 nm output of an optical parameter
      generator and optical parameter amplifier pumped by a Nd: YAG laser was obtained.
      The vibration frequency and the inharmonic coefficients of the ground electronic
      state of NO were calculated from the results of the spectral ascription. They are
      omega"e = (1 904. 7 +/- 7. 3) cm(-1), omega"e chi"e = (14.2 +/- 1.2) cm(-1), and
      omega"e y"e = -(0.021 8 +/- 0.009 1) cm(-1) respectively. It was found for the
      first time that the intensity of the spectral lines departs from the Frank-Condon
      principle due to the self-absorption of NO molecules. The spectral line of A
      2sigma (v' = 0) --> X 2 II (v" = 0) transition disappears in the fluorescence
      spectra. But it appears gradually with decreasing the sample pressure and the
      distance from the laser-gas interaction volume to the receiving window. All of
      these provide an important reference for monitoring NO by the technique of laser
      induced fluorescence.

PMID- 16883869
TI  - [Analysis of the characters of organic matter in water using spectral
      fluorescence signature and fitting Gaussian].
AB  - A sort of analytical method of fast diagnosis of organic matter in water is
      discussed. The total luminescence spectra (TLS) of water samples in combination
      with laser induced fluorescence (LIF) measurements using 532 nm wavelength
      excitation source were measured in the laboratory. The spectra of dissolved
      organic matter (DOM) and chlorophyll a (Chl a) were pointed out and obtained with
      spectral fluorescence signature (SFS) technique. The spectrum of water Raman
      scattering and fluorescence of DOM and Chl a were separated from TLS with fiting
      Gaussian of the least squares method, and a high correlation coefficient
      excelling 0.996 4 was obtained. The results indicated the possibilities of water
      quality monitoring in real time and on line based upon SFS technique and fitting
      Gaussian of the least squares method.

PMID- 16883871
TI  - [Synthesis, characterization and luminescence properties of coordination
      compounds of rare earth with p-tert-butyl-calix[8] arene].
AB  - Fourteen solid coordination compounds of rare earth(Sm3+, Eu3+, Tb3+ and Dy3+ and
      Ln3+ (La3+, Gd3+ and Y3+)-doped Tb3+ with p-tert-butyl-calix[8] arene (LH8) have
      been synthesized and characterized. Elemental analysis, rare erth complexometry,
      1H NMR spectra and TG-DTA have been studied. The results suggest that the
      complexes have the composition of [RE2 (LH2)(DMSO)5]DMSO, [RE2 (LH2) (DMF)5]
      2DMF, [LnTb (LH2) (DMSO)5] DMSO and [LnTb (LH2) (DMF)5] 2DMF respectively.
      Fluorescence spectrum suggests that the Tb3+ complexes have characteristic
      luminescence, and its fluorescence intensity is enhanced after doping with La3+,
      Gd3+ and Y3+. The influence of the doping ions and two neutral ligands (DMSO and
      DMF) has also been discussed. In addition, the fluorescence lifetime of some
      complexes has been investigated.

PMID- 16883872
TI  - [Synthesis and spectral characterization of rare-earth-ortho-amino phenylbenzoate
      2,2'-bipyridine complexes].
AB  - The solid rare-earth complexes were synthesized using rare-earth ions (RE=Tb, Nd,
      Sm, La) reacting with ortho-amino phenylbenzoic acid (L) and 2,2'-bipyridine
      (bipy). Their compositions were confirmed and the spectral properties were
      characterized by element analysis, infrared and ultraviolet absorption spectra,
      and DTA-TGA. The fluorescent properties of complexes TbL3 and TbL3 x bipy x 3H2O
      were also measured and discussed. The result shows that the fluorescence
      intensity of TbL3 x bipy 3H2O is stronger than that of TbL3.

PMID- 16883874
TI  - [Studies on the interaction of the metal complex of hydrazide of podophyllic acid
      with DNA].
AB  - The interaction between the metal complex of hydrazide of podophyllic acid and
      calf thymus (CT) DNA was studied by using absorption spectra, fluorescence
      spectra and DNA heat denaturation. It was found that the intensity of the maximal
      absorption peaks from absorption spectra is weakened in the presence of the metal
      complex of hydrazide of podophyllic acid compared with that in the absence of the
      metal complex. All the experimental results show that the intercalation mode was
      proved to exist between HDPP-Ni complexes and CT DNA.

PMID- 16883873
TI  - [Plasma glutathione of patients with coronary heart disease measured by
      fluorospectrophotometer].
AB  - The standard samples of reduction form glutathione (GSH) and oxidization form
      glutathione (GSSG) were scanned with full-wavelength range to determine the
      excitation wavelength lambda(ex) 334.4 nm, the emission wavelength lambda(em) 424
      nm, and the spectral bandwidth 5 nm respectively. Phosphate buffer saline (PBS)
      of pH 8. 3 served as buffer solution. GSH was incubated for 30 min with 100
      microL o-phthaldehyde (OPA) of 10 mmol x L(-1) methyl alcohol solution for
      derivatization, and then fluorescence intensities were measured. With standard
      glutathione concentration being independent variable and fluorescence intensity
      being dependent variable, the linear equations for GSH and GSSG were deduced:
      Y(GSH) = 6.9 + 8.6X (r2 = 0.994) and Y(GSSG) = 6.2 + 17.2X (r2 = 0.999). Standard
      curves were done hereby. The plasma glutathione of three groups was then
      measured, and GSH/ GSSG redox potential was calculated according to Nernst
      equation. The results indicated that, from normal control group to prophase
      coronary heart disease group, then to coronary heart disease group, the GSH and
      GSH/GSSG ratio gradually reduced, GSSG and GSH/GSSG redox potential gradually
      increased (more positive) (all P < 0.05), and the redox potential shifted to
      oxidization direction along with the development of coronary heart disease. This
      fluorospectrophotometry method showed simple operation, and fine precision and
      accuracy.

PMID- 16883875
TI  - [Determination of calcium concentration in water solution by laser-induced plasma
      spectroscopy].
AB  - With the experiment setup the calcium concentration in water solution was
      measured, based on a Nd: YAG Q-switched solid laser as the exciting light. The
      experiment results show that the concentration of calcium has a good linear
      relationship with its spectral intensity, the maximum relative errors of
      measurement are 3.79%, and the linear regression coefficients are 0. 992 87. In
      addition, laser induced plasma spectroscopy (LIPS) demonstrated convenient
      operation, and reliable and higher precision measurement of calcium concentration
      in water solution.

PMID- 16883876
TI  - [Determination of trace elements in sika bone powder by inductively coupled
      plasma mass spectrometry with microwave digestion].
AB  - Contents of trace elements in sika bone powder were determined with microwave
      digestion and inductively coupled plasma mass spectrometry. Under the optimum
      conditions, the detection limits (3sigma, n = 11) are in the range of 0. 000 6-1.
      498 ng x mL(-1) with relative standard deviations of 1.7%-6.8%. The recoveries
      are between 91% and 109%. The analytical results of national certified reference
      demonstrated the applicability of the proposed method.

PMID- 16883877
TI  - [Direct determination of lead and cadmium in soil by slurry-sampling graphite
      furnace atomic absorption spectrometry using matrix modification technique].
AB  - A method for the direct determination of lead and cadmium in soil by slurry
      sampling graphite furnace-atomic absorption spectrometry using NH4 H2 PO4 as
      matrix modifier was developed. The effects of slurry stability, particle size of
      sample, matrix modifiers, ashing temperature, atomization temperature and common
      coexistent components on the signal intensities of lead and cadmium were
      investigated. The apparent activation energies of lead and cadmium were measured
      based on the linear relationship between the logarithm value of atomization peak
      time and atomization temperature. The mechanism of matrix modification was
      discussed. Under optimized conditions, the detection limit was 9.05 x 10(-10) g x
      mL(-1) for Pb and 1.76 x 10(-11) g x mL(-1) for Cd. The recoveries were in the
      range of 91%-97% for Pb and 93%-109% for Cd. The relative standard deviations
      were in the range of 4.2%-7.8%.

PMID- 16883878
TI  - [Determination of lead in water samples by graphite furnace atomic absorption
      spectrometry after cloud point extraction with dithizone].
AB  - Cloud point extraction was used for the preconcentration of lead after the
      formation of a complex with dithizone in the presence of surfactant Triton X-114,
      and then the lead was determined by graphite furnace atomic absorption
      spectrometry. The conditions affecting the separation and detection process were
      optimized. Separation of the two phases was accomplished by centrifugation for 15
      min at 4 000 rpm. Upon cooling in an ice-bath, the surfactant-rich phase became
      viscous. The aqueous phase could then be separated by inverting the tubes. Later,
      a solution of methanol containing 0.1 mol x L(-1) of HNO3 was added to the
      surfactant-rich phase up to 0.5 mL. The samples were determined by graphite
      furnace atomic absorption spectrometry with NH4H2PO4 and Mg(NO3)2 as a chemical
      modifier. At pH 8.0, the preconcentration of only 10 mL sample in the presence of
      0.05% Triton X-114 and 20 micromol x L(-1) dithizone permitted the detection of
      0.089 microg x L(-1) lead. The enhancement factors were 19.1 times for lead. The
      calibration graph using the preconcentration system for lead was linear with a
      correlation coefficient of 0.998 from levels near the detection limits up to at
      least 30 microg x L(-1). The regression equation was A = 0.026 1c (microg x L(
      1)) + 0.010 6. The proposed method has been applied to the determination of lead
      in water samples.

PMID- 16883879
TI  - [Determination of trace copper and cadmium in water by flame atomic absorption
      spectrometry coupled with flow injection on-line preconcentration using air
      segmentation].
AB  - The flow injection on-line preconcentration with a knotted reactor (KR) system
      for the determination of copper and cadmium in water by flame atomic absorption
      spectrometry (FAAS) was described in the present paper. The precipitation
      preconcentration of trace copper and cadmium was achieved by on-line merging of
      the sample and ammonia solutions. The resultant precipitates were on-line
      collected by a knotted reactor (KR) without filtration, and then the authors used
      a process of air segmentation. A solution of 1 mol x L(-1) HNO3 was employed to
      dissolve the collected precipitates and to deliver the analyte into the FAAS
      system for on-line detection. With a sample loading flow rate of 4.4 mL x min(-1)
      and a preconcentration time of 90 s, the enhancement factor was 34 (for Cu) and
      36 (for Cd) as compared with the conventional FAAS method. The detection limits
      (3sigma) are found to be 1.9 and 0.3 microg x L(-1) for copper and cadmium
      respectively. The precision (RSD, n = 11) was found to be 2.3% at the level of
      30.0 microg x L(-1) of Cu (II), and 2.6% at the level of 20.0 microg x L(-1) of
      Cd (II). The proposed method has been successfully applied to the determination
      of Cu (II) and Cd (II) in water samples.

PMID- 16883880
TI  - [Determination of nine trace elements in Dioscorea opposita thumb by flame atomic
      absorption spectrophotometry].
AB  - The contents of the potassium, calcium, sodium, magnesium, copper, zinc, iron,
      manganese, strontium and nickel in Dioscorea opposita thumb were determined. The
      relative standard deviation(RSD) of the first eight contents is 0.43%, 1.10%,
      4.41%, 0.68%, 1.44%, 1.88%, 1.29% and 0.03% respectively, and the percentage
      recovery is 90.0%-111.0%. The method is convenient and accurate. It can be used
      to determine the trace elements simultaneousy in Dioscorea opposita thumb.

PMID- 16883882
TI  - [The reflection spectrometer and quantitative analysis design].
AB  - The reflection spectrometer with optical fibre transmission was designed and used
      in quantitative analysis. The reflection spectrometry was applied to the
      determination of reducing sugar in samples based on the reduction reaction of the
      reducing sugar with Fehling's reagent. The reduction reaction was carried out in
      a micro-reaction cell, and the reddish colored Cu2O produced was settled at the
      bottom of the reaction cell. The reflectance R(infinity), which is directly
      proportional to the amount of Cu2O produced, was measured by the reflection
      spectrometer. The fundamental principle, effect factors, and experimental
      conditions of the method were discussed. Linear relationship was obtained in the
      range of 20-120 microg of reducing sugar. The special features of this method
      were its simplicity in operation, relatively high sensitivity of determination,
      and the use of small amount of reagent. Satisfactory results were obtained in its
      application to the analysis of wine and honey samples.

PMID- 16883881
TI  - [Adsorption and coprecipitation of dissolved metals with jarosite under
      conditions simulating sewage sludge bioleaching].
AB  - The inoculation of Acidithiobacillus ferrooxidans and the addition of Fe2+ as
      their substrates accelerated the solubilization of Zn, Cu and Cr from sewage
      sludge. However, a decrease in Cu removal from 91% to 60% with time elapse could
      be observed in the late process, which appeared simultaneously with the formation
      of jarosite resulting from hydrolysis of Fe3+. The tested jarosite was
      synthesized by using bacterial oxidation of Fe2+ by resting A. ferrooxidans in
      acid solution (pH 2.5) under conditions stimulating sludge bioleaching.
      Adsorption edge measurement showed that only less than 9% of Cu2+ was adsorbed
      onto jarosite in the pH range of 2.0-2.5, indicating that adsorption mechanism
      could not explain fully re-sorption of Cu2+ (about 31%) in the anaphase of
      bioleaching process. In the coprecipitation studies, when jarosite was
      precipitated in the presence of Cu2+ (10 mg x L(-1)), a significant amount of Cu
      (44.6%) was incorporated into the precipitate. Coprecipitation of jarosite with
      Cu2+ was the predominant process by which soluble Cu was partially re-sorpted by
      jarosite in the anaphase of bioleaching process.

PMID- 16883883
TI  - [Suppositional sutural construction and application in the three-dimensional
      finite element model of craniofacial complex].
AB  - OBJECTIVE: The purpose of this study was to explore suppositional sutural
      construction and protraction in the three-dimensional finite element model of
      craniofacial complex. METHODS: Combining spiral CT scanning technology with the
      three-dimensional finite element method, three-dimensional FEM model of
      craniofacial complex was developed for analysis. In the model, craniofacial
      sutures were constructed through the MSC. Patran program and different mechanical
      properties of sutures were applied. Under the same loading condition, bone
      displacements of the maxilla were calculated. RESULTS: A three-dimensional FE
      model of craniofacial complex, comprising teeth and craniofacial sutures, was
      developed. The displacement of the skeletal structures with sutures was
      significantly larger than that without sutures. CONCLUSIONS: The construction of
      craniofacial sutures in the three-dimensional finite element model of
      craniofacial complex could improve the accuracy of finite element model, which
      set up good foundation for biomechanical studies of craniofacial complex.

PMID- 16883884
TI  - [The application of three-dimensional skull model in the treatment of
      craniofacial malformation].
AB  - OBJECTIVE: This study was to construct a geometric skull model with 3-dimension
      scanning and rapid-prototyping (RP) technology and also to evaluate the
      significance and further application of surgery simulation in the treatment of
      complex craniomaxillofacial malformation. METHODS: Twelve patients with complex
      craniomaxillofacial malformation were involved. The data obtained with CT
      scanning were transferred to a personal computer for surface rendering 3
      dimension reconstruction. A geometric model was manufactured by selective laser
      sintering using rapid-prototyping device. Surgery simulation was performed both
      on the model and in the computer. Accordingly, a custom implant and an implant
      template, when needed, were constructed with the computer-aided design (CAD) and
      prefabricated with computer-aided manufacture (CAM) process. RESULTS: Surgery
      simulation made the operation shorter, the complications lower and the outcome
      better. CONCLUSIONS: Skull model provides great convenience in the treatment of
      cranio-maxillofacial malformation.

PMID- 16883885
TI  - [Total calvarial reconstruction for sagittal synostosis].
AB  - OBJECTIVE: To study the technique of total calvaria reconstruction for sagittal
      synostosis. METHODS: 11 children with sagittal synostosis were treated. The David
      II procedure was used to reconstruct the calvarial gap in 6 cases; Osteotomies
      with reversal change was performed on 2 cases; Plum-plasty of the calvaria was
      performed on 3 cases. RESULTS: The 11 cases were cured with satisfactory head
      shape. CONCLUSIONS: The David II procedure is applicable for patient of 1
      approximately 3 months. The technique of floating skull flap plasty and plum
      plasty of the calvaria can be performed on patients older than 3 months.

PMID- 16883886
TI  - [Evaluation of temporomandibular joint function after condylectomy for condylar
      hyperplasia].
AB  - OBJECTIVE: To investigate the temporomandibular joint (TMJ) function of the
      condylar hyperplasia patients after condylectomy. METHODS: Twelve patients with
      condylar hyperplasia were included in this study. Before and after condylectomy,
      they were examined and the Fricton' s Craniomandibular Index (CMI) was calculated
      to assess the functional disorder of TMJ. RESULTS: (1) The facial asymmetry was
      improved after condylectomy. The morphological symmetry of the bilateral condyle
      and ramus was displayed by X-ray examinations. There was new cortex formed on the
      surface of the operated condyle. (2) The TMJ function was improved in terms of
      Fricton's DI and CMI, which decreased from 0.131 and 0.066 to 0.042 and 0.021
      respectively (P < 0.05). CONCLUSIONS: Condylectomy is an effective method to
      remedy facial asymmetry and, at the same time, improve the TMJ function of the
      condylar hyperplasia patients.

PMID- 16883887
TI  - [Lower capsular contracture of miniprostheses as compared with the conventional
      silicone implant].
AB  - OBJECTIVE: To determine if miniprostheses would form a capsule of significantly
      different biophysical, biochemical and histologic properties than the
      conventional silicone implant. METHODS: Four miniprostheses (experimental group)
      and one big silicone implants (control 1 group) were separately implanted beneath
      the panniculus carnosus muscle of 30 rabbits. After 3 months, measures related to
      contracture and capsular histology were performed on anesthetized animals.
      RESULTS: Baker ranking, capsular incision width and capsular thickness of the
      control groups were evidently higher than that of experimental groups (P < 0.01).
      Implant compression of the control groups was evidently lower than that of the
      experimental group. Histology revealed a thinner, more flexed capsule around the
      miniprostheses as compared with big silicone implants. CONCLUSIONS: The
      miniprostheses form a looser and thinner capsule than the conventional silicone
      implant.

PMID- 16883888
TI  - [Removing breast foreign body resulted from augmentation with polyacrylamide
      hydrogel injection and silicone prosthesis implantation at one stage].
AB  - OBJECTIVE: This study was to investigate an operation, in which removing breast
      cysts of foreign body resulted from augmentation with polyacrylamide hydrogel
      injection was performed simultaneously with silicone prosthesis implantation
      under SEPS endoscope in order to relieve tissue injury and increase the accuracy
      of clearance. METHODS: Eight patients were included in this study. Preoperative
      type B ultrasound examination was performed to mark the mass. Through an axillary
      approach, the cysts of foreign body that were distributed in the subcutaneous
      tissue, breast or muscle were separated and ablated under SEPS endoscope. After
      removal of the foreign body, a silicone implant was located submuscularly for
      breast augmentation. RESULTS: The operations were completed without hematoma and
      infection. Follow-up of the eight patients for 3 to 12 months showed that
      preoperative symptoms relating to the injected material, such as breast pain,
      lump and asymmetry, have no longer existed. The shapes of the breasts were
      satisfactory. CONCLUSIONS: We believe that endoscope-assisted mammoplasty offers
      more satisfactory clinical results with less injury, less morbidity, less scars,
      more accuracy and greater patient acceptance.

PMID- 16883889
TI  - [Clinic applications of primary breast reconstruction with a subpectoral silicone
      tissue expander].
AB  - OBJECTIVE: To investigate the application of breast reconstruction that permits
      the surgeon to expand and recruit sufficient tissue for modified radical
      mastectomy, skin-sparing mastectomy and asymmetry deformity. METHODS: Placement
      of round tissue expander in subpectoral position below. Overexpansion of tissue
      expander to match over 30% approximately 50% opposite breast. After 3 months,
      removal of tissue expander and replacement with permanent implant. RESULTS:
      Postoperative follow-up for 3 months to 2 years demonstrated satisfactory results
      in all the cases. CONCLUSIONS: The breast reconstruction with a subpectoral
      silicone tissue expander is an ideal treatment to modified radical mastectomy,
      skin-sparing mastectomy and asymmetry deformity. The women can obtain a restored
      breast to approximate a full opposite breast and avoids a major distant surgical
      intervention and additional scars. Tissue expansion should be cautiously used in
      cases of patients with irradiated chest skin.

PMID- 16883890
TI  - [One-stage repair of unilateral cleft lip and nasal deformity].
AB  - OBJECTIVE: To investigate the method for simultaneous correction of nasal
      deformity and unilateral cleft lip so as to decrease the secondary operation for
      the deformity. METHODS: The Millard procedure (or Millard plus triangle flap
      insertion) was used to repair the unilateral cleft lip. Through the incisions,
      the greater alar and nasalis were repositioned to the normal anatomical
      positions. The deviated septum and columella were corrected by cutting the
      abnormal attachment of the orbicular muscle of mouth to the anterior nasal spine.
      The mattress sutures through the tip of the columella and ala nasi helped to
      recover the shape of the nostril. RESULTS: 108 patients were treated with this
      method. They aged from one month to 19 years, included 30 with second degree
      cleft lip and 78 with third degree cleft lip. The follow-up for as long as 3
      years showed satisfactory results. CONCLUSIONS: This technique can eliminate the
      severe cleft nasal deformity and elevate the displaced alar cartilage at the time
      of lip repair without interference with nasal growth. It is recommended for the
      treatment of unilateral cleft lip with severe nasal deformity.

PMID- 16883892
TI  - [Individual repair technique of microform cleft lip: state of art].
AB  - OBJECTIVE: To explore an technique to repair the microform cleft lip (MCL).
      METHODS: The individual method was used to repair the MCL, a contrastive research
      was carried to analyzed the result. RESULTS: It was found that the form of the
      cupid's bow was good, and the configure of the upper lip was reconstructed. The
      deficit of the orbicularis muscle was overcame and the function was satisfying by
      this procedure. Symmetry was recovered. CONCLUSIONS: Individual technique is an
      available method to repair the microform cleft lip. Furthermore, this technique
      is also promising to repair the other kinds of cleft lip.

PMID- 16883891
TI  - [Analysis of Millard II technique for correcting secondary deformities of
      unilateral cleft lip].
AB  - OBJECTIVE: To analyze the Millard II technique for correcting secondary
      deformities of unilateral cleft lip. METHODS: The Millard II technique was used
      to correct secondary deformities of unilateral cleft lip in 42 patients from
      March of 2003 to September of 2004. Dissection was made between the alar
      cartilage and skin, and the alar cartilage was suspended. RESULTS: The
      postoperative follow-ups with 3 approximately 6 months revealed good results of
      the symmetrical nostrils and philtrums, prolonged columella nasi, good-shaped
      cupid's bow, and invisible scar. CONCLUSIONS: The Millard II technique could be
      an ideal method to correct secondary deformities of unilateral cleft lip.
      Releasing and suspending alar cartilage spontaneously at the same time can
      correct nasal deformity adequately.

PMID- 16883893
TI  - [Experimental study on the survival of venous flap with different pedicle
      styles].
AB  - OBJECTIVE: To study a new method of venous flap that is improved on its
      persistence and quality. METHODS: New Zealand white rabbits were subdivided
      randomly into 4 groups. All rabbits were operated by harvesting a flap from the
      latero-abdominal wall and then sutured it in the original position. Group A: the
      superficial epigastric vein in the pedicle was left open (only one inflow vein
      remained). Group B: the pedicle vein of the proximal and distant end were left
      open (keeping an inflow vein and a principal out). Group C: the pedicle vein and
      a tributary vein were left open (keeping an inflow vein and a tributary outflow
      vein). Group D: the pedicle vein and two tributary veins were left open (keeping
      an inflow vein and two tributary outflow veins). Survival rate, MDA of the
      tissue, histology and ultra-microstructure were examined. RESULTS: Survival rate
      of A, B, C, D were improved in order. Statistic difference is significant (P <
      0.05) between group and group other than C and D. The content of MDA was
      heightened with statistically significant differences (A > B > C > D) among the
      four groups 8 hours postoperatively, but fell back to the normal level in group D
      and C and kept a high level in group A and B at 72 hour postoperatively.
      Histology and ultra-microstructure exam showed that degeneration of collagen
      fiber and karyopyknosis of cell is more obvious in Group A and Group B than Group
      C and Group D. CONCLUSIONS: The higher survival rate of venous flap is possible
      by designing the more reasonable venous flap outputs pedicles which can alleviate
      the high tension dropsy and maintain the valid equilibrium of pour with flow in
      the venous flap.

PMID- 16883894
TI  - [An animal model of venous congested flap for long-term microcirculation study].
AB  - OBJECTIVE: To set up a venous congested flap model to study the mechanism of
      necrosis through long-term microcirculation observation. METHODS: A specially
      deviced chamber was assembled to one side of the ears in an adult white rabbit,
      about 7 approximately 10 days after the operation the congested flap model was
      made and the microcirculatory status of the flap was dynamically observed under a
      vivo-microscope for a long time. RESULTS: The venous crisis phenomenon of flap
      was well studied and the microcirculation of the flap was observed carefully,
      finally the variational rule of the congestion flap microcirculation was made
      clear. CONCLUSIONS: The model could well simulate the venous crisis flap in
      clinic, and the microcirculation could also be observed for a long time.

PMID- 16883895
TI  - [A hemifacial transplantation model in hares].
AB  - OBJECTIVE: To design an animal model to study the facial transplantation of
      allografts in rabbits. METHODS: Livid blue rabbits and New Zealand white rabbits
      was applied as experiment animal, to harvest hemifacial composite-tissue flap
      based in the common external carotid artery with the branch of the external
      mandibular artery and auricularis magna artery, then allotransplantation was
      performed with the livid blue rabbits as recipient while new Zealand rabbits as
      donor, the immunosuppressive agent comprised ciclosporin, azamun and prednisone.
      25 couples of rabbits were divided three groups. Group A, 5 couples of rabbits,
      no administered immunosuppressive agent and the artery anastomosis with end-to
      end. Group B, 10 couples of rabbits, administered immunosuppressive agent and the
      artery anastomosis with end-to-end. Group C, 10 couples of rabbits, administered
      immunosuppressive agent and the artery anastomosis with end-to-side.
      Postoperative, to observe the survive ratio of animal and composite-tissue flap,
      verified the practicability of model further. RESULTS: The blood supply of
      hemifacial composite-tissue flap is rich after allotransplantation. The survive
      ratio wasn't different with different procedure of the external carotid artery
      anastomosis. CONCLUSIONS: This is a successful model of composite face flap
      transplantation in the rabbits.

PMID- 16883896
TI  - [Drug resistance analysis of staphylococcus infection in our hospital from 2003
      to 2005].
AB  - OBJECTIVE: To explore the change in mobility of staphylococcus and its drug
      resistance etiology investigation and clinical treatment. METHODS: The routine
      biochemical identification was used for staphylococcus differentiation. Minimal
      inhibitory concentrations was used for drug-resistance determination. Some drug
      resistance determination were detected by K-B method. The inducible resistance of
      erythromycin to clindamycin was checked by D-test. RESULTS: Staphylococcus was in
      the first place in the hospital infection. The rates of methicillin-resistant
      staphylococcus were 54.1%. The drug-resistance rates of staphylococcus to
      penicillin, oxacillin, erythromycin, tetracycline, ciprofloxacin, gentamicin,
      clindamycin, SMZCO, chloramphenicol, vancomycin, teicoplanin antibacterials were
      93.2%, 54.1%, 85.1%, 56.7%, 45.9%, 48.6%, 58.1%. 45.9%, 31.1%, 0%, 0%. D-test
      positive rate was 37.9%. CONCLUSIONS: The results are helpful in study of
      pathogenic bacteria and drug resistance characteristics in staphylococcus
      infection.

PMID- 16883898
TI  - [A basic study and clinical trial of 585 nm pulsed dye laser in the treatment of
      congestive scars].
AB  - OBJECTIVE: To study the biological effects of 585 nm pulsed dye laser (FLPDL) in
      the treatment of congestive scar. METHODS: By histological study, collagen VG
      staining and microvascular staining, we investigated the changes of collagen
      fibers and the density of microvessels in the congestive scars after FLPDL
      treatment. RESULTS: Histological and immunohistochemistry examinations showed
      that FLPDL achieved normal vascularity in the scar after over 3 times of
      treatment. CONCLUSIONS: PDL treatment can change fundamentally the physiology of
      wound healing if applied in the early phases.

PMID- 16883897
TI  - [Application of integra for reconstruction of burn scar contracture].
AB  - OBJECTIVE: Introducing a comprehensive technique to reconstruct burn scar
      contracture or deformities using integra (artificial dermis) with large epidermal
      skin grafting or ulth-thin split-skin. METHODS: The wounds following contracture
      scar or deformities excised or loose were covered with the integra which was
      flattened and fixed perfectly, after a 2 approximately 4-week period, the out
      layer was removed then covered with large sheets of epidermal grafts, which was
      of thickness from 0.0028 inc to 0.0048inc (0.07 approximately 0.12 mm), or ulth
      thin split-skin of about 0.006inc (0.15 mm) thickness, harvested using the
      electric or air power dermatome, the edge of the graft sheet attached together
      with the borders of wound using nanoparticles-Ag-gauze stripe adding sutures of
      the 5-0 threads or the skin stapler, dressed with vaseline gauzes in the inner
      layer and the nano-particles Ag gauze on the outer surfaces. RESULTS: Nineteen
      sites of 15 cases including 5 sites in trunk and 14 sites in extremities from
      1999.8 to 2003.6 were treated using this technique in this study, the wound areas
      following scar excised was about 10 cm x 25 cm approximately 30 cm x 75 cm, of
      them 12 cases covered with a large sheet of ultr-thin split-skin (in early time)
      and 7 cases with a large sheet of epidermal grafting and all of them was
      survival. The colour and texture of the reconstruction sites were very good and
      can be compared favorably with normal skin after a half year-four year following
      up period, because all donor sites healing without scarring, the appearance in
      the epidermal graft donor is better than that in split-thickness skin donor.
      CONCLUSIONS: Integra with large sheets of epidermal grafts applied for scar
      contracture disformities is an effective and useful method, especially the
      epidermal grafts offered a satisfying result in the donor healing.

PMID- 16883899
TI  - [Experimental study of acellular xenogenic dermal matrix and allogeneic sclera as
      wrapping materials for hydroxy apatite implantation].
AB  - OBJECTIVE: To observe the experimental results and histopathological changes of
      acellular xenogenic dermal matrix (X-ADM) and allogeneic sclera used as wrapping
      materials of hydroxy apatite (HA) ocular implants in New Zealand white rabbits.
      METHODS: Twenty-four rabbits received unilateral eye enucleating and the sockets
      were implanted with HA spherical implants wrapped with either acellular xenogenic
      dermal matrix or allogeneic sclera at random. The rabbits were examined for
      inflammation and implant exposure and sacrificed at 1, 2, 4, 6, 8 and 12 weeks
      after implantation. The sockets with the grafts were exenterated and the
      specimens were assessed histopathologically and ultrastructurally with light or
      transmission electron microscopy for the changes in inflammation reaction and
      vascularization. RESULTS: Compared to allogeneic sclera at the same stage of
      implantation, acellular xenogenic dermal matrix demonstrated more active and
      earlier growth of fibroblasts and new vessels with abundant collagen deposition.
      There were few inflammatory cells and no rejection was found. CONCLUSION: This
      experiment showed that the acellular xenogenic dermal matrix, with fast
      neovascularization and low immunity, can be an ideal material of ocular implant
      and a good substitute for allogeneic sclera.

PMID- 16883900
TI  - [The experiment of porcine keratinocytes cultured on porcine small intestinal
      submucosa in vitro].
AB  - OBJECTIVE: To investigate the feasibility of acellular porcine small intestinal
      submucosa (SIS as bioscaffold of tissue engineering skin. METHODS: The second
      passage keratinocytes were seeded on SIS, after seeded for 11, 13, 15, 17 days,
      the keratinocytes/SIS composites were observed by dye directly, histopathology,
      immunohistochemical studies with monoclonal antibodies against laminin and
      transmission electron microscope (TEM). RESULTS: At eleventh day, keratinocytes
      were growth very well on the surface of SIS, there are 2-3 cell layers on partial
      of the SIS surface, the continued expression of laminin can be detected between
      the keratinocytes and the surface of SIS. After 13, 15, 17 days this stratified
      structure increased, cells contact more closely, the tonofibrils in cells,
      desmosome between cells and the basal membrane between the keratinocytes and the
      surface of SIS can be seen with TEM. CONCLUSIONS: SIS is a kind of good
      bioscaffold in the culture of porcine keratinocytes in vitro.

PMID- 16883901
TI  - [Effect of traditional Chinese medicine in improving quality of life of patients
      with non-small cell lung cancer in late stage].
AB  - OBJECTIVE: To observe the effect of traditional Chinese medicine (TCM) in
      improving quality of life of patients with non-small cell lung cancer (NSCLC) in
      III or IV stage, for establishing TCM therapeutic regimen on late NSCLC. METHODS:
      A total of 294 patients in 6 hospitals were randomly assigned into three groups,
      99 in the TCM group treated with TCM according to disease and syndrome
      differentiation, 92 treated with chemotherapy in the western group and 103
      treated with combined therapy of TCM and chemotherapy in the integrative group.
      Six items, including physical status, social/family status, intercourse with
      physicians, emotional status, functional status and additional concerning status,
      were investigated and analyzed by using Functional Assessment of Cancer Therapy
      lung (FACT-L). RESULTS: The scores of social/family status and intercourse with
      physicians were insignificantly different in all three groups before and after
      treatment (P > 0.05). The improvement of physical status in the TCM group, and
      that of emotional status, functional status and additional concerned status in
      the integrative medicine group were superior to those in the other groups (P<
      0.05). CONCLUSION: TCM has certain antagonistic effect on the adverse reaction of
      chemotherapy, and it can improve the quality of life of patients to certain
      extent.

PMID- 16883902
TI  - [Clinical study on effects of tiepi fengdou granule/capsule combined with
      chemotherapy and/or radiotherapy in treating lung cancer with Qi-Yin asthenia
      syndrome].
AB  - OBJECTIVE: To study the clinical efficaly and safety of Tiepi Fengdou Granule
      (TFG) and Capsule (TFC) combined with chemotherapy and/or radiotherapy in
      treating lung cancer patients with Qi-Yin asthenia syndrome (QYAS). METHODS:
      Eighty patients were randomly assigned into 3 groups: the TFG group (32 cases),
      the TFC group (32 cases) and the Shengmai Capsule control group (16 cases).
      Changes of symptoms of QYAS, main symptoms of lung cancer, Karnofsky scoring as
      well as the blood routine test were observed. RESULTS: The total effective rate
      of symptom improving in the TFG group and the TFC group was 81.2% and 93.3%
      respectively, showing insignificant difference between the 2 groups (P > 0.05),
      but both were higher than that in the Shengmai Capsule control group (50.0%, P <
      0.05 and P < 0.01). Additionally, as compared with those before treatment, the
      neutrophil count increased and the lymphocytes count obviously decreased in the
      TFC group after treatment (all P < 0.05). CONCLUSION: Both dose-forms of the
      remedies, TFC and TFG, have significant effects in treating lung cancer with
      QYAS, but with insignificant difference between them.

PMID- 16883903
TI  - [Effect of modified xiaoyao powder on electrogastrographic picture and
      pharmacokinetic characteristics of ferulic acid in patients with functional
      dyspepsia of gan-qi stagnation with pi-deficiency syndrome type].
AB  - OBJECTIVE: To investigate the mechanism of Modified Xiaoyao Powder (MXP) on
      electrogastrogram (EGG) and pharmacokinetic characteristics of ferulic acid (FA)
      in patients with functional dyspepsia (FD) of Gan-qi stagnation with Pi
      deficiency syndrome type (FD-GP). METHODS: The study was conducted following
      method of pharmacodynamics and pharmacokinetics synchronous determination. The 20
      patients with FD-GP and 21 healthy volunteers enrolled were orally administrated
      with MXP to observe the changes in symptom scores, EGG and pharmacokinetic
      characteristics of FA in patients using gastrointestinal analyzer and high
      performance liquid chromatography (HPLC) before and after treatment. RESULTS:
      After treatment, the symptom scores of patients significantly decreased (P <
      0.01). EGG showed that the average amplitude of peak and dominant frequency, etc.
      at the monitoring points, including gastric body, lesser curvature and the near
      gastric antrum part of greater curvature, etc. were lower than the normal range,
      the changes were especially obvious and would be worsened after meals (P < 0.01).
      After treatment by MXP, all the above indexes were improved either before or
      after meals. The pharmacokinetic parameters of FA in patients of FD-GP before
      treatment were lower than those in the healthy control group (P < 0.05) and they
      were insignificant different by MXP comparing with those in the healthy control
      group. CONCLUSION: MXP is effective not only in improving clinical symptoms and
      EGG, but also on pharmacokinetic parameters of FD-GP patients.

PMID- 16883904
TI  - [Clinical study on effect and safety of bushen qiangji granule in treating
      ankylosing spondylitis patients].
AB  - OBJECTIVE: To evaluate the efficacy and safety of Bushen Qiangji Granule (BQG) in
      treating ankylosing spondylitis (AS) patients with Shen-deficiency and blood
      stasis syndrome. METHODS: A randomized controlled and single-blinded prospective
      clinical trial was carried out on 68 patients, who were randomly assigned into
      the BQG group treated with BQG alone and the combined treated (CT) group treated
      with BQG and sulfasalazine, six-month medication was successively applied to both
      groups. The therapeutic effects were evaluated before treatment and at the end of
      the 1st, 3rd and 6th month of the treatment. RESULTS: The total effective rate
      was 81.82% in the BQG group and 86.82% in the CT group after 6 months of
      treatment, showing no significant difference between the two groups, but that
      after 1 months of treatment in the BQG group was lower than that in the combined
      group (15.15% vs. 27.59%, P < 0.01). Bath AS disease activity index (BASDAI),
      Bath AS function index (BASFI), and clinical symptoms such as ache and morning
      stiffness, as well as indexes of Schober test, activity of thoracic cage, finger
      ground distance, erythrocyte sedimentation rate (ESR) and Creactive protein (CRP)
      in both groups were improved remarkably. BQG showed a time-dependant' effect, the
      therapeutic effect intensified as the time went by (P < 0.05 or P < 0.01).
      Moreover, the effect initiating time was earlier in the CT group than that in the
      BQG group. CONCLUSION: BQG has satisfactory efficacy, good safety and compliance,
      and is convenient for administering, therefore, it has broad applying prospect
      with high exploiting value.

PMID- 16883905
TI  - [Analysis of the function of vascular endothelial cells in coronary heart disease
      patients of blood-stasis syndrome].
AB  - OBJECTIVE: To explore the function of vascular endothelial cell (VEC) in patients
      with coronary heart disease (CHD) of Xin-blood-stasis syndrome. METHODS: Some
      vasoactive substances produced by VEC were detected and analyzed in patients with
      CHD of or without Xin blood stasis syndrome in group A (n=112) and group B
      (n=108) respectively, also in patients with non-CHD but of Xin-blood-stasis
      syndrome in group C (n=110), and healthy persons in group D (n=100), including
      nitric oxide (NO), endothelin (ET), angiotensin H (Ag II), soluble intercellular
      adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule -1
      (sVCAM-1). RESULTS: The abnormality degree of ET, Ag II , sICAM-1 and sVCAM-1 in
      various groups showed such a tendency as group A> group B> group D (P < 0.01 or P
      < 0.05), while no significant difference in these criteria between group A and
      group C was shown (P > 0.05). CONCLUSION: The vasoactive substances secreted by
      VEC are closely related to the formation and progression of CHD, and are likely
      to be important pathological markers of blood-stasis syndrome in CHD.

PMID- 16883906
TI  - [Effects of syndrome dependent umbilical sticking with shizhang cataplasm and
      xuzhang cataplasm in treating Cirrhosis caused ascites].
AB  - To investigate the effects of Shizhang Cataplasm (SC) and Xuzhang Cataplasm (XC)
      in treating liver cirrhosis caused ascites of excessive syndrome (ES) type and
      deficient syndrome (DS) type respectively. METHODS: All the 77 patients (37 of ES
      type and 40 of DS type) enrolled were treated by conventional treatment but with
      restrictive use of diuretics. SC and XC were given respectively to 26 patients of
      ES type and 26 of DS type additionally by umbilical sticking, they were regarded
      as the treated group, and those (11 of ES type and 14 of DS type) not received
      the cataplasm treatment were regarded as the control group. The changes of
      symptoms, body weight, abdominal perimeter and amount of urine before and after
      treatment were observed, and amount of ascites was examined with B-ultrasound to
      evaluate the efficacy according to comprehensive grading criteria. Also, the
      toxicity was observed. RESULTS: Sixty-two cases completed the full course, 15
      were withdrawn. As compared with the corresponding control group, body weight,
      abdominal perimeter and amount of ascites decreased, while amount of urine and
      flatus discharging increased remarkably in the treated group (P < 0.05). The
      comprehensive efficacy in patients of ES type was better than that in DS type (P
      < 0.05). The effective rate of grade I/II was 7.1% and 9.1% for patients in the
      control group of DS type and ES type respectively, while it was 57.2% and 69.2%
      in the treated group of DS and ES type respectively. Better therapeutic effect
      was shown in patients of ES type treated with SC. CONCLUSION: SC and XC showed
      good assistant effects in treating patients with liver cirrhosis caused ascites
      of ES and DS type respectively.

PMID- 16883908
TI  - [Effect of acupuncture combined behavior intervention on children with autism].
AB  - OBJECTIVE: To investigate the effect of acupuncture combined behavior
      intervention on children with autism. METHODS: Patients were treated by "Jin's
      three-needling" as the main measure with the assistance of behavior intervention,
      and the changes were compared among the three groups (29 cases in combination
      group, 15 cases in acupuncture group and 10 cases in intervention group) before
      and after treatment of various factors and scores estimated by the autism
      behavior checklist (ABC) and autism development checklist (ADC). RESULTS: In the
      combination group, the total scores of ABC and most factors of ABC including body
      movement, social communication and language factor were improved significantly
      after treatment (P < 0.01), but there was no significant changes in sense factor
      and daily life self-caring factor (P > 0.05). Comparison of most items of ADC
      before and after treatment also showed significant difference (P < 0.01).
      CONCLUSION: Acupuncture combined behavior intervention has better therapeutic
      efficacy in the treatment of children with autism.

PMID- 16883907
TI  - [Clinical study on treatment of early diabetic nephropathy by tangshenling
      combined with telmisartan].
AB  - OBJECTIVE: To study the effects and the possible mechanism of Tangshenling (TSL)
      combined with telmisartan on early diabetic nephropathy (DN). Methods Eighty-one
      patients with early DN were randomly assigned into the control group (n=40)
      treated by telmisartan alone and the treated group (n=41) treated by TSL combined
      with telmisartan, and the conventional western therapy was given to all patients
      in both groups. Changes before and after treatment in symptoms and levels of
      urine albumin excretion rate (UAER), urine transforming growth factor beta1 (TGF
      beta1), retinol binding protein (RBP) and beta2-microglobulin (beta2-MG), fasting
      blood glucose (FBG), serum creatinine (SCr), blood lipids, plasma atrial
      natriuretic peptide (ANP), serum collagen type IV (Col-IV) and TGF-beta1 were
      observed. RESULTS: Before treatment, no significant difference was shown in all
      these indexes between the treated group and the control group. After 8 weeks of
      treatment, the effective rates in symptoms improvement were higher in the treated
      group than those in the control group (P < 0.05 or P < 0.01); UAER, urine RBP,
      beta2-MG and TGF-beta1, serum TC, TG, Col-IV and TGF-beta1, and blood pressure
      were significantly lowered in both groups after treatment (P < 0.05 or P < 0.01);
      and the treated group showed a better effect than the control group in improving
      all the above-mentioned indexes except the blood pressure (P < 0.05); but there
      was no significant difference in the changes of FBG, SCr and blood pressure
      between the 2 groups (P > 0.05); after treatment, plasma ANP significantly
      lowered in the treated group (P < 0.01), while there was no significant change of
      that in the control group (P > 0.05). Conclusion Combination of TSL and
      telmisartan has a better effect than telmisartan on DN in early stage. Its
      mechanism might be related to the decrease of ANP and TGF-beta1 and improvement
      of lipids metabolism and renal tubular interstitial pathological changes.

PMID- 16883909
TI  - [Exploration on molecular mechanism of Epimediun flavonoids in regulating
      adrenocortical regeneration in rats with inhibited hypothalamic-pituitary-adrenal
      axis using oligonucleotide microarrays].
AB  - To investigate the regulatory effects of epimedium flavonoids (EF) on
      adrenocortical regeneration in rats with inhibited hypothalamic-pituitary-adrenal
      (HPA) axis. METHODS: Cell distribution in cell cycle and cell apoptotic rate were
      measured with PI stain and flow-cytometry; apoptosis cells were showed by in situ
      terminal-deoxynucleotidyl transferase-mediated deoxy-uridine triphosphate
      fluorescene nick end labeling assay (TUNEL), and the genome-wide gene mRNA
      expression was detected by oligonucleotide microarrays. RESULTS: Compared to the
      normal control, adrenal cells isolated from the HPA axis inhibited model group
      were arrested in Go/GI phase, and showed a higher apoptotic rate (P < 0.05).
      After treated with EF, cells in G0/G1 phase decreased and those in G2/M phase
      increased (P < 0.01), and the elevated apoptotic rate reduced significantly (P <
      0.05). TUNEL assay showed the number of apoptotic cells per section was 4.67 1.53
      in the normal control group, 70.67 +/- 9.29 in the model group, and 18.67 +/-
      7.64 in the EF-treated group respectively (n=3). Gene expressions in adrenal were
      mostly restrained in the model group, including 7 cytocycle promoting genes,
      including V-ras, V-jun, etc., while after treatment with EF, 6 cytocycle
      promoting genes, 1 anti-apoptotic gene, and genes that closely related with
      adrenocortical regeneration as IGF-II and FGF7 and their receptors, as well as 7
      steroid biosynthesis participated genes were all up-regulated. Conclusion EF can
      accelerate adrenocortical cell proliferation, inhibit its apoptosis, and promote
      steroid biosynthesis so as to enhance adrenocortical regeneration in HPA axis
      inhibited rats, which may contribute to the beneficial effects of EF in
      protecting adrenocortical function during glucocorticoid withdrawal.

PMID- 16883910
TI  - [Effect of maixinkang capsule on Ca2+ and mitochondrial membrane potential in
      liver cells of ApoE(-/-) mice].
AB  - OBJECTIVE: To observe the effect of Maixinkang Capsule (MXK) on Ca2t
      concentration and mitochondrial membrane potential in liver cells of ApoE(-/-)
      mice. METHODS: Liver cells from ApoE(-/-) mice were separated using collagenase
      digestive method. After the primary cells were cultured for 8 days in vitro, the
      concentration of 10% MXK contained rat's serum was added into the culture fluid.
      The Ca2+ concentration and mitochondrial membrane potential in liver cells after
      48-hr culture were measured by confocal laser scanning microscopy with Flou-3 and
      Jc-1 as probes. RESULTS: MXK could decrease Ca2+ concentration in liver cells,
      which was significantly different to that in the control group (P < 0.01).
      Meanwhile, MXK could significantly improve mitochondrial membrane potential in
      liver cells (P < 0.01). There was no obvious dose-effect relationship shown in
      both effects of MXK. CONCLUSION: MXK can decrease Ca2+ concentration and improve
      the mitochondrial membrane potential in liver cells of ApoE(-/-) mice so as to
      regulate the lipids and prevent the occurrence and development of hyperlipemia
      and atherosclerosis.

PMID- 16883912
TI  - [Effect of jiangu granule on levels of urinary deoxypyridinoline and osseous
      intigrin beta1 mRNA expression in Ovariectomized osteoporosis model rats].
AB  - OBJECTIVE: To investigate the regulatory effect of Jiangu Granule (JGG) on
      osteoblast and its effect on bone absorption on the molecular level and from
      aspect of bone metabolism. METHODS: Osteoporosis model SD rats established by
      ovariectomy were interfered by drug. Levels of urinary deoxypyridinoline (D-Pyr)
      and osseous integrin beta1 (Itgbeta1) mRNA expression were detected by ELISA and
      in situ hybridization, respectively. RESULTS: Level of urinary D-Pyr increased (P
      < 0.01) and osseous Itgbeta1 mRNA expression decreased significantly in the model
      rats. After treatment with JGG for 12 weeks, the D-Pyr levels in them decreased
      significantly (P < 0.05), while the quantity of osteoblasts and the expression of
      Itgbeta1 mRNA in bone tissue increased obviously. Conclusion JGG can not only
      decrease the catabolism of collagen fiber type I in bone matrix, but also promote
      the osteogenic activity of osteoblast. So, it can improve or reverse the
      pathological tendency of osteogenesis shortage caused by E2 reduction to play its
      action in strengthening bone.

PMID- 16883913
TI  - [Effects of salvianolic acid B on signal transduction induced by transforming
      growth factor-beta1 and platelet-derived growth factor- BB in hepatic stellate
      cells of rats].
AB  - OBJECTIVE: To explore the anti-hepatic fibrosis mechanisms of salvianolic acid B
      (SA-B). METHODS: Hepatic stellate cells (HSCs) isolated from rats were primarily
      cultured in uncoated plastic culture dish for 7 days, then were incubated with
      10(-6) mmol/L SA-B and stimulated with 10 ng/ml transforming growth factor-beta1
      (TGF-beta1) or platelet-derived growth factor-BB (PDGF-BB). Expressions of
      extracellular-regulated kinase (ERK) and its phosphorylation in HSC, and
      expressions of TGF beta1, receptor I (TbetaR I) and II (TbetaR II) and PDGF
      receptor beta (PDGFR-beta) on the surface of HSC induced by TGF-beta1 or PDGF-BB
      were detected with Western blot assay. RESULTS: SA-B inhibited the
      phosphorylation of ERK1/2 in HSC primary normally cultivated for 9 days
      stimulated or un-stimulated by TGF-beta1, but could not affect the expressions of
      TbetaR I and TbetaR II on the HSC surface; it down-regulated the expression of
      PDGFR-beta, but had no obvious effect on the phosphorylation of ERK1/2 in those
      HSC stimulated or un-stimulated by PDGF-BB. CONCLUSION: SA-B inhibits the ERK
      signal transduction induced by TGF-beta1 in HSC, which is independent of the
      expressions of TbetaR on HSC surface and also free from the ERK signal
      transduction stimulated by PDGF-BB. And its inhibition on PDGF-BB signal
      transduction in HSC is by way of restraining the expression of PDGFR in HSC.

PMID- 16883911
TI  - [Experimental study on effect of er'zhi tiangui granule in improving quality of
      oocyte and its correlation with level of insulin-like growth factor-1R mRNA
      expression in ovary of mice].
AB  - OBJECTIVE: To explore the mechanism of Er'zhi Tiangui Granule (ETG) in improving
      the quality of oocyte. METHODS: Ninety mice were randomly divided into 6 groups.
      The number of high-quality oocytes was comparatively observed in the 1st
      experimental group and the 1st control group; the embryonic cleavage rate was
      observed in the 2nd experimental group and the 2nd control group and the quantity
      of insulin-like growth factor-1R mRNA (IGF-1R mRNA) expression in ovarian
      granular cells was determined by using in situ hybridization in the 3rd
      experimental group and the 3rd control group. RESULTS: The high-quality oocytes
      rate, the embryonic cleavage rate and the quantity of IGF-1R mRNA expression in
      the three paired groups was (78 +/- 8)% vs (71 +/- 5)%, (88 +/- 3)% vs (83 +/-
      5)%, 0.4890 +/- 0.0454 vs 0.4439 +/- 0.0283, respectively. The difference between
      the experimental groups to the respective control groups was significant (all P <
      0.05), and positive correlation was shown between the high-quality oocytes rate
      and the quantity of IGF-1R mRNA expression. CONCLUSION: The mechanism of ETG in
      improving the quality of oocyte may be related with the elevation of IGF-1R mRNA
      level in ovarian granular cells.

PMID- 16883914
TI  - [Effects of radix Astragali injection on apoptosis of lymphocytes and immune
      function in patients with systemic lupus erythematosus].
AB  - OBJECTIVE: To investigate the effect of Radix Astragali Injection on apoptosis of
      lymphocytes and immune function in treating patients with systemic lupus
      erythematosus (SLE). METHODS: Eighty SLE patients were randomly assigned into the
      routine treatment group (RT) treated with conventional therapy and the Radix
      Astragali treated group (RA) treated with Radix Astragali Injection besides
      routine treatment. The expressions of Fas and Bcl-2 antigen on lymphocytes and
      the changes of T lymphocyte subsets in peripheral blood before and after
      treatment were observed. RESULTS: After treatment, the expression of Fas antigen
      on lymphocytes significantly lowered (P < 0.01), and that of Bcl-2 antigen, CD4+
      lymphocyte subset and CD4+ / CD8+ ratio significantly increased in both groups
      (all P < 0.01). However, the changes of Fas antigen expression, CD4+ and CD4+ /
      CD8+ ratio were more significant in the RA group than those in the RT group (P <
      0.05). CONCLUSION: Radix Astragli Injection can enhance the inhibitory function
      of corticosteroid/immunosuppressant on apoptosis, and regulate the ratio and
      function of T lymphocyte subsets to normal range, which may be a useful approach
      for enhancing the efficacy of treatment to SLE.

PMID- 16883915
TI  - [Clinical observation on effect and safety of combined use of wenxin granule and
      amiodarone for conversion of auricular fibrillation].
AB  - OBJECTIVE: To observe the clinical effect of the combined use of amiodarone and
      Wenxin Granule (WXG) in auricular fibrillation (AF) conversion and its safety.
      METHODS: Two hundred and twenty-four patients, in whom AF lasted for less than 1
      year, were enrolled and randomly assigned into two groups, 112 in each group.
      Patients in the treated group were treated with WXG and amiodorane and the others
      in the control group were orally administered with amiodarone alone. The
      accumulative conversion rate of AF and adverse reaction were monitored during the
      6-month observation period. RESULTS: Six-month observation was completed in 109
      cases in the treated group and 107 in the control group, while 3 cases and 5
      cases in the two groups were dropped out respectively. The difference of
      accumulative AF conversion rates between the two groups become significant early
      after one month medication (P < 0.05), and was 65.1% and 47.7% respectively after
      6-month of treatment (P < 0.05). Inter-group significant difference was also
      shown in the aspects of average conversion time, dosage of amiodarone required
      and the occurrence of adverse reaction (P < 0.05). CONCLUSION: Combined use of
      WXG and amiodarone has a better effect in improving conversion rate of AF,
      shortening conversion time and decreasing the required dosage of amiodarone in
      treating AF as compared with the treatment with amiodarone alone, and by which
      the adverse reaction of long-term using amiodarone could be avoided.

PMID- 16883916
TI  - [Clinical observation on treatment of active systemic lupus erythematosus with
      haoqin qingdan decoction].
AB  - OBJECTIVE: To observe the therapeutic efficacy and safety of Haoqin Qingdan
      Decoction (HQD) in treating active stage of systemic lupus erythematosus (SLE).
      METHODS: One hundred and twenty patients with SLE were randomly assigned into two
      groups, the treated group receiving HQD and prednisone, and the control group
      receiving prednisone and cyclophosphamide (CTX), both were treated for 3 months.
      SLE disease activity index (SLEDAI), various immunological indexes, blood and
      urine routine, hepatic and renal function, as well as the other adverse reaction
      of the treatment were observed. RESULTS: The total effective rate in the treated
      group was 81.67% (49/60), while 76.67% (46/60) in the control group, showing
      insignificant difference between the two groups. SLEDAI, erythrocyte
      sedimentation rate (ESR), complement 3 (C3), 24-hr urinary protein excretion and
      anti-double strain deoxyribonucleic acid (dsDNA) antibody were improved in the
      treated group, and no obvious adverse reaction was shown. CONCLUSION: HQD is
      obviously more effective in treating active stage of SLE with high safety.

PMID- 16883917
TI  - [On establishing comparative reference system for syndrome classification study
      from the thinking characteristics of syndrome differentiation dependent therapy].
AB  - To create a comparative referential system for syndrome classification study by
      viewing from the thinking characteristics of TCM on syndrome differentiation
      dependent therapy (SDDT), through analyzing the thinking process of SDDT, and the
      basic features of disease, syndrome and prescription, combining the basic
      principles of modern evidence-based medicine and feasibility of establishing
      integrative disease-syndrome animal model. The practice of creating a comparative
      referential system based on clinical efficacy of prescription was discussed
      around syndrome pathogenesis and its relationship with disease and prescription,
      which was one of the important scientific problems in TCM syndrome study. The
      authors hold that, it may be one of the available approaches for the present
      study on integration of disease with syndrome by way of insisting on the thinking
      pathway of stressing the characteristics of TCM and intermerging with modern
      scientific design; on taking the efficacy of prescription as the comparative
      reference system to accumulate and improve unceasingly according to the TCM
      method of syndrome diagnosis inferred from effect of prescription with reverse
      thought (i.e., to differentiate syndrome from the effect of prescription), and
      thus build up the syndrome diagnostic standard on the solid clinical and
      scientific base.

PMID- 16883918
TI  - [Some suggestions on clinical study of traditional Chinese medicine].
AB  - According to the international accepted criteria, some suggestions were provided
      in this paper on the clinical study of traditional Chinese medicine. Firstly,
      allocate the participants randomly, rather than deliberately perform that to
      balance the baseline characteristics in groups. Secondly, use the international
      standard to evaluate the clinical effectiveness, rather than just use the simple
      criteria as cure rate, markedly effective rate, and effective rate. Thirdly,
      record and manage the missing data with proper statistical methods. Fourthly,
      objectively report the results of study, especially avoiding selective bias. In
      addition, the low limit effects should be avoided when assessing the effects of
      TCM in treating difficult and uncertain diseases; furthermore, the ethical
      problems should also be considered.

PMID- 16883919
TI  - [Analysis of citations referenced in articles published in Chinese Journal of
      Integrated Traditional and Western Medicine from 2001 to 2004].
AB  - OBJECTIVE: To investigate the referential rule and the informative absorbing
      capacity of the Chinese Journal of Integrated Traditional and Western Medicine
      (CJITWM), and analyze the characteristics of literature requirement of scientists
      working in integrated Chinese and Western medicine (ICWM) field offering
      suggestions on literary utilization. METHODS: Citation analysis was used to
      analyze the references cited in 1825 articles published in CJIM from 2001 to 2004
      according to their time sequence of publishing. RESULTS: The citation rate was
      53.64%, and 9.51% citations per article. Most of the citations were mainly cited
      from journals (85.38%) and books (13.4%). The Price Index was 49.22%, and the
      self-citation rate for author and periodical were 3.63% and 7.77% respectively.
      CONCLUSION: CJITWM is a highly authorized and representative professional
      academic periodical in the field of ICWM. The citations are mainly cited from
      periodicals written in Chinese or English, they are of good novelty and quality,
      but the citation rate should be further improved.

PMID- 16883920
TI  - [Review on treatment of unstable atherosclerotic plaque with traditional Chinese
      medicine].
AB  - Rupture of unstable atherosclerotic plaque is an essential pathogenetic mechanism
      of acute coronary syndrome (ACS), thereby, to stabilize the vulnerable plaque is
      of great importance for prevention and treatment of ACS. Recent study has shown
      the multi-target effects of traditional Chiese medicine intervention in
      stabilizing unstable atherosclerotic plaque is promising. The literatures
      involving this topic in recent years were reviewed in this paper.

PMID- 16883921
TI  - Consider the public health implications of tuberculosis.

PMID- 16883922
TI  - Beta2 agonists in the treatment of asthma.

PMID- 16883923
TI  - Interventions to facilitate smoking cessation.
AB  - Tobacco use, primarily cigarette smoking, is the leading cause of preventable
      morbidity and mortality in the United States, and nearly one third of those who
      try a cigarette become addicted to nicotine. Family physicians, who see most of
      these patients in their offices every year, have an important opportunity to
      decrease smoking rates with office-based interventions. The U.S. Public Health
      Service recommends that primary care physicians use the five A's (Ask, Advise,
      Assess, Assist, and Arrange) model when treating patients with nicotine
      addiction. Physicians can improve screening and increase cessation rates by
      asking patients about tobacco use at every office visit. Behavior modification
      can improve long-term smoking cessation success; even brief (five minutes or
      less) advice on smoking cessation during an office visit can increase cessation
      rates. The effectiveness of nonpharmacologic treatments generally is lower;
      therefore, pharmacotherapy is recommended for smokers who are willing to attempt
      cessation, unless medical contraindications exist. The pharmacologic agents
      approved by the U.S. Food and Drug Administration for treatment of tobacco
      dependence include bupropion (a non-nicotine therapy) and nicotine replacement
      therapies in the form of a gum, patch, nasal spray, inhaler, and lozenge. These
      agents have similar long-term success rates.

PMID- 16883924
TI  - Information from your family doctor. Tips to help you quit smoking.

PMID- 16883925
TI  - Primary care for lesbians and bisexual women.
AB  - For the most part, lesbians and bisexual women face the same health issues as
      heterosexual women, but they often have difficulty accessing appropriate care.
      Physicians can improve care for lesbians and bisexual women by acknowledging the
      potential barriers to care (e.g., hesitancy of physicians to inquire about sexual
      orientation and of patients to disclose their sexual behavior) and working to
      create a therapeutic physician-patient relationship. Taking an inclusive and
      nonjudgmental history and being aware of the range of health-related behaviors
      and medicolegal issues pertinent to these patients enables physicians to perform
      relevant screening tests and make appropriate referrals. Some recommendations,
      such as those for screening for cervical cancer and intimate partner violence,
      should not be altered for lesbians and bisexual women. Considerations unique to
      lesbians and bisexual women concern fertility and medico-legal issues to protect
      familial relationships during life changes and illness. The risks of suicidal
      ideation, self-harm, and depression may be higher in lesbians and bisexual women,
      especially those who are not open about their sexual orientation, are not in
      satisfying relationships, or lack social support. Because of increased rates of
      nulliparity, the risks of conditions such as breast and ovarian cancers also may
      be higher. The comparative rates of alcohol and drug use are controversial.
      Smoking and obesity rates are higher in lesbians and bisexual women, but there is
      no evidence of an increased risk of cardiovascular disease.

PMID- 16883926
TI  - Information from your family doctor. Health care for lesbians and bisexual women.

PMID- 16883927
TI  - Chronic musculoskeletal pain in children: part II. Rheumatic causes.
AB  - Primary care physicians should have a working knowledge of rheumatic diseases of
      childhood that manifest primarily as musculoskeletal pain. Children with juvenile
      rheumatoid arthritis can present with painless joint inflammation and may have
      normal results on rheumatologic tests. Significant morbidity may result from
      associated painless uveitis, and children with juvenile rheumatoid arthritis
      should be screened by an ophthalmologist. The spondyloarthropathies (including
      juvenile ankylosing spondylitis and reactive arthritis) often cause enthesitis,
      and patients typically have positive results on a human leukocyte antigen B27
      test and negative results on an antinuclear antibody test. Patients with acute
      rheumatic fever present with migratory arthritis two to three weeks after having
      untreated group A beta-hemolytic streptococcal pharyngitis. Henoch-Schbnlein
      purpura may manifest as arthritis before the classic purpuric rash appears.
      Systemic lupus erythematosus is rare in childhood but may cause significant
      morbidity and mortality if not treated early. Nonsteroidal anti-inflammatory
      drugs and physical therapy may be useful early interventions if a rheumatic
      illness is suspected. Family physicians should refer children when the diagnosis
      is in question or subspecialty treatment is required. Part I of this series
      discusses an approach to diagnosis with judicious use of laboratory and
      radiologic testing.

PMID- 16883928
TI  - Opportunities to improve outcomes in sickle cell disease.
AB  - Sickle cell disease represents a spectrum of inherited hemoglobin disorders. The
      pathophysiology involves abnormalities not just in red blood cells but also
      vascular endothelium, white blood cell function, coagulation, and inflammatory
      response. Known sequelae of sickle cell disease include invasive infections,
      painful episodes, acute chest syndrome, strokes, and chronic pulmonary
      hypertension. Preventive strategies that decrease the risk of infection are the
      routine use of daily antibiotics until five years of age, immunization of
      children with the 7-valent pneumococcal conjugate vaccine in addition to the 23
      valent polysaccharide pneumococcal vaccine, annual influenza vaccination after
      six months of age, and meningococcal vaccination after two years of age. A
      significant advance in stroke prevention is the use of transcranial Doppler
      ultrasonography to identify asymptomatic, at-risk children who should be
      considered for chronic blood transfusions. Chronic transfusion therapy for
      primary or secondary stroke prevention requires careful surveillance for iron
      overload and chelation therapy. Patients with chest pain, fever, or respiratory
      symptoms and new pulmonary infiltrates require aggressive medical management for
      acute chest syndrome. Pain management still represents an important area for
      aggressive treatment using sickle cell disease-specific guidelines. Newer
      treatments include hydroxyurea therapy to decrease the frequency of painful
      episodes and associated comorbidities, and hematopoietic cell transplantation for
      a limited subset of patients. Family physicians play a crucial role in
      instituting evidence-based preventive care strategies, initiating timely
      treatment of acute illness, recognizing life-threatening episodes, and providing
      a medical home for multidisciplinary management.

PMID- 16883929
TI  - Information from your family doctor. When your child has sickle cell disease.

PMID- 16883930
TI  - Soft tissue mass over right brow. Dermoid cyst.

PMID- 16883931
TI  - [Three-dimensional ultrasound tomography--preliminairy report].
AB  - Three-dimensional ultrasound tomography of the eye is a new advanced technique of
      ocular ultrasonography. The aim of this work was to present a new interesting
      ultrasound unit with possibility of three-dimensional ultrasound tomography,
      after half year experience with this system. The article describes scanning
      techniques using acommercial 3-D ultrasound system (OTI-Scan 1000) and presents
      how to assess the dimensions of intraocular structures anddocument them
      volumetrically.

PMID- 16883933
TI  - [Results of bimanual phacoemulsification with intraocular lens implantation
      through the micro incision].
AB  - PURPOSE: To evaluate the postoperative results of bimanual, cold
      phacoemulsification with foldable lens implantation through 1.7 mm incision.
      MATERIAL AND METHODS: Thirty four bimanual cold phacoemulsifications with Acri.
      Smart (AcriTec) IOL implantation through 1.7 mm incision were performed in the
      Department of Ophthalmology, Medical University of Lodz, between March and May
      2004. In the group of 34 patients, 24 were women and 10 were men. The mean age of
      patients was 67 years (range between 42 and 77). Preoperative visual acuity
      ranged from 0.5/50 to 5/10. Mean visual acuity was 0.3. Preoperative astigmatism
      ranged from 0.15 to 2.3 diopters (mean 0.7). Preoperatively, nuclear density was
      estimated according to LOCS III classification. Twenty patients (59%) had 1 to 3
      nuclear density, and 14 (41%) had 4 to 6 nuclear density. All surgeries were
      performed with Oertli machine using the burst mode with a sleeveless phaco tip.
      Postoperative examinations were conducted on the 1st and the 7th day, and I month
      after the surgery. Visual acuity, astigmatism, status of the cornea and IOL
      centration were evaluated. RESULTS: No intraoperative complications were
      observed. All 34 patients maintained corneal transparency with no signs of
      thermal damage around the wound. Visual acuity improved in all cases. Mean visual
      acuity in 33 patients who had no coexisting ocular diseases I month after surgery
      was 0.98 and the mean induced astigmatism was 0.2 diopters. In all cases IOLs
      were very well centred. CONCLUSIONS: Bimanual phacoemulsification is a very safe
      method allowing to minimise corneal incision. Using Acri. Smart IOLs, the induced
      astigmatism is very small, almost imperceptible to patients.

PMID- 16883932
TI  - Cool phaco in combined phacoemulsification and vitrectomy surgery.
AB  - PURPOSE: The aim of this paper is to present the use of bimanual
      phacoemulsification technique in combined phacoemulsification and vitrectomy
      surgery. MATERIAL AND METHODS: Combined phacoemulsification and vitrectomy
      procedure was performed in 20 eyes. Phacoemulsification was performed through two
      paracenteses. Soft acrylic intraocular lenses were implanted into the capsular
      bag through a paracentesis 1.8 mm wide. Standard three-port pars plana vitrectomy
      followed. Indications for vitrectomy were diabetic retinopathy, retina
      detachment, uveitis, macula hole. All surgeries were performed as one-day
      surgeries. Follow-up lasted six months. RESULTS: Visual acuity improved in 19/20
      eyes (95%). The achieved functional results were similar to that achieved in
      standard phacoemulsification combined with vitreoretinal surgery. Surgery time
      did not differ significantly from time needed to perform a standard procedure.
      The bimanual technique allowed the stablization of the anterior chamber during
      vitreoretinal surgery. No serious postoperative complications occurred.
      CONCLUSIONS: The presented method improves the quality of combined surgery,
      ensures stability of the anterior chamber, reduces postoperative astigmatism,
      lowers the risk of inflammation.

PMID- 16883934
TI  - [Efficacy of intravitreal triamcinolone acetonide in the visualization of the
      vitreous during pars plana vitrectomy].
AB  - PURPOSE: To retrospectively evaluate the efficacy of triamcinolone acetonide (TA)
      injection during pars plana vitrectomy, to facilitate the visualization of the
      internal limiting membrane (ILM), residual vitreous cortex (RVC) and preretinal
      membranes. MATERIAL AND METHODS: Pars plana vitrectomy was performed in 164
      patients due to rhematogenous retinal detachment, vitreous hemorrhage, macular
      hole, lens luxation, endophthalmitis, intraocular foreign body, malignant
      glaucoma, preretinal membrane and proliferative diabetic retinopathy. After
      surgical separation of the posterior vitreous and removal of any visible
      epiretinal membrane, TA suspension was injected over the posterior pole into the
      vitreous cavity. Then, visualized RVC was removed and ILM peeling was performed.
      RESULTS: Upon intravitreal injection of TA, vitreous and ILM could be visualized
      by numerous particles of TA dispersed as white specks. RVC and ILM were
      completely removed in all patients. No complications related to the use of TA
      were encountered, even after complex procedures such as, vitrectomy combined with
      scleral buckling or phakoemulsification surgery in a long term follow up.
      CONCLUSIONS: Intraoperative visualization of RVC and ILM with intravitreal TA was
      found to be a useful adjunct to pars plana vitrectomy. This technique may
      facilitate both removal of epiretinal membrane and separation of vitreous,
      especially in patients with undetached vitreous.

PMID- 16883935
TI  - [Pathomorphology of membranes appearing in proliferative vitreoretinopathies].
AB  - Immunohistochemical techniques were used to investigate the cell content of
      epiretinal membranes occuring in proliferative vitreoretinopathy (PVR) and
      proliferative diabetic retinopathy (PDR). Ten epiretinal membranes were obtained
      during surgery from eyes with PVR and five from eyes with PDR. This material was
      studied histopathologically and immunohistochemically. Retinal pigment epithelial
      cells, glial cells, macrophages, T lymphocytes and type IV collagen were
      identified in these membranes. The findings indicate that the cells mentioned
      possess a potential role in creating vitreoretinal membranes in PVR and PDR.

PMID- 16883936
TI  - Evaluation of blood flow in the ophthalmic artery and central retinal artery in
      children with retinopathy of prematurity.
AB  - PURPOSE: To evaluate blood flow parameters in the ophthalmic artery and central
      retinal artery in children with retinopathy of prematurity (ROP). MATERIAL AND
      METHODS: The study comprised 57 premature children born between 24 and 33 weeks
      of gestation, with birth weight from 600 g to 1660 g, including 42 preterm
      children with retinopathy in stage 1, 2, 3 and 3 "plus" and 15 preterm children
      without retinopathy. Color Doppler ultrasonography (USG-CD) was used to measure
      in the studied vessels maximal systolic velocity (Vmax), end-diastolic velocity
      (Vmin) and resistance index (RI). RESULTS: Statistically significantly (p < 0.05)
      higher values of Vmax were seen in the ophthalmic artery and central retinal
      artery in preterm children with retinopathy in stage 2 and 3, as compared with
      other children. In preterms with dilation and tortuosity of posterior blood
      vessels in stage 3 "plus" ROP Vmax in both studied vessels was lower and was
      comparable to that in stage 1 ROP and in children without retinopathy. RI in the
      ophthalmic artery in children with ROP in stage 2 and 3 was statistically
      significantly higher (p < 0.05) from its values seen in other groups, and for the
      central retinal artery RI did not differ statistically significantly.
      CONCLUSIONS: The conducted USG-CD measurements revealed that in children with
      retinopathy of prematurity haemodynamic parameters of blood flow in the
      ophthalmic artery and central retinal artery differ in relation to disease stage
      of advancement, and in relation to the status of blood vessels in the eye fundus.
      The clinical implications of these results, however, need to be confirmed in long
      term studies, in order to determine the sensitivity, specificity and
      repeatability of this method, as well as to establish the diagnostic standards.

PMID- 16883937
TI  - [Diode laser photocoagulation for retinopathy of prematurity--outcomes in one
      year observation].
AB  - PURPOSE: To evaluate structural and functional outcomes in one-year old patients,
      treated for retinopathy of prematurity (ROP) with transpupillary diode laser
      photocoagulation. MATERIALS AND METHODS: 58 children (116 eyes) 12 months old,
      after treatment for ROP with diode laser photocoagulation, were examined. Both,
      functional outcome (visual acuity--basing on the examination with Teller Acuity
      Card Procedure), and structural outcome were evaluated. The cycloplegic
      refraction was examined in all cases. RESULTS: We have found good functional
      outcome in 81.9%, and good structural outcomes in 96.5% of examined eyes. 64.6%
      of eyes had hyperopic refractive error, and 31% were myopic. CONCLUSIONS: Diode
      laser photocoagulation is an effective method of treatment for ROP.

PMID- 16883938
TI  - [The analysis of failure diode laser treatment of active phase of retinopathy of
      prematurity].
AB  - PURPOSE: The aim of this study was to analyze risk factors influencing diode
      laser treatment of active phase of retinopathy of prematurity. MATERIALS AND
      METHODS: 106 premature infants were treated with the use of diode laser at
      Department of Neonatology since 1.01.2003-30.11.2004. The mean gestational age
      was 27.3, mean birth weight 1022 g. The earliest age of laser therapy was 37th
      day of life and the latest one 104th day (mean 64.3 days). 18 neonates were
      excluded from the study because they were from other departments, and 2 because
      they died. The results of treatment of the rest 86 children were evaluated. The
      occurence of retinal detachment or macular ectopy was classified as unfavorable
      outcome. RESULTS: The complete remission was obtained in 143 eyes (83.2%),the
      macular ectopy was diagnosed in 10 eyes (5.8%), the retinal detachment in 19 eyes
      (11%). Children with unfavorable outcomes were divided in two groups. The first
      one included 6 extremely immature infants, born between 24 to 25th week of
      gestation. The ROP in this group was diagnosed in I zone with plus disease. The
      second group included children with gestation age from 28 to 32 Hbd. 9 of them
      had severe infection (sepsis, congenital pneumonia, urinary tract infection), 1
      serious maternal history (R type of diabetes). The procedure of laser therapy was
      performed on average at 72th day of life at the first group, and at 50th day at
      the second one. CONCLUSIONS: (1) Important risk factors of treatment failure of
      active phase of retinopathy of prematurity, is low gestational age and infections
      which take place in perinatal period. (2) In the second group of infants
      (gestational age from 28-32 Hbd), with treatment failure the retinopathy of
      prematurity occured much more earlier then in the group with successful
      treatment. (3) When making decision of the patient treatment besides estimation
      of the eye fundus and the progress of changes, we should also consider risk
      factors which have influence on retinopathy of prematurity, after treatment.

PMID- 16883939
TI  - [Results of 10 years observation of organ of sight in prematurity].
AB  - PURPOSE: (1) To compare the incidence of refractive errors and the orthoptic
      condition in ten-year-old children, born prematurely and treated with cryotherapy
      versus children, whom did not apply such a procedure. (2) To estimate condition
      of the extraocular muscles. MATERIAL AND METHODS: A group of 60 prematurely born
      children was divided into 2 subgroups: I--30 children treated with cryotherapy,
      II--30 no treatment was applied. All the children had anterior segment, fundus
      and visual acuity examined. Refraction following cycloplegia was evaluated.
      Visual acuity and orthoptic status was assessed. RESULTS: In the group of
      prematurely born children who had retinopathy in the infantile age and were
      treated with cryotherapy, refractive errors were frequently observed. In over
      half of those children squint or impaired eye movement were found. In the group
      of children who required no cryotherapy the percentage of those with refractive
      errors was similar. CONCLUSIONS: In prematurely born children with retinopathy
      refractive errors and squint occur quite often. Prematurely born children should
      be subject to ophthalmologic follow-up throughout their childhood.

PMID- 16883940
TI  - [Visual acuity and binocular vision in children with pseudophakia].
AB  - PURPOSE: To evaluate the results of cataract surgery in children with IOL
      implantation. MATERIALS AND METHODS: Our research involved 106 children (156
      eyes) with congenital and traumatic cataract, in age from 18 months to 18 years,
      who underwent cataract surgery with intraocular lens implantation. We evaluated
      visual acuity for far vision and binocular vision after surgery. RESULTS: Visual
      acuity over 0.5 in unilateral congenital cataract was found in 27.25%, in
      traumatic cataract in 73%, whereas in bilateral congenital cataract visual acuity
      over 0.5 we received in 75% of operated children. Full binocular vision was
      obtained in children with good visual acuity (0.5 and more), with appropriate
      alignment of the eyes: 13.1% in unilateral congenital cataract, 45.4% in
      traumatic cataract and 55% in congenital bilateral cataract. CONCLUSIONS:
      Cataract surgery with intraocular lens implantation results in increase of visual
      acuity and in achievement binocular vision, if surgery is carried out in the
      early period, after it had been diagnosed.

PMID- 16883941
TI  - [Problems in surgical management of persistent hyperplastic primary vitreous in
      children].
AB  - PURPOSE: To evaluate the surgical techniques that allows safe, effective removal
      of lens and retrolenticular fibrotic membranes in eyes with PHPV in children.
      MATERIAL AND METHODS: A total of 31 children (18 boys and 13 girls) with PHPV and
      cataract in one eye were divided into 2 groups, according to treatment modality.
      High frequency ultrasonography were used to identify anatomic correlates in the
      eyes--before operation. Limbal cataract extraction combined with vitrectomy and
      removalof embryonic remnants was carried out in 17 eyes, and a posterior pars
      plana approach in 14 eyes. RESULTS: In group with anterior approach, the most
      serious complication was corneal decompensation, in the next group--retinal
      detachement. CONCLUSIONS: The anterior and the posterior surgical technique to
      remove cataract and tenacious retrolenticular membranes was effective but
      associated with high risk of intraoperative and postoperative complications.
      Although the surgical intervention is necessary to prevent progressive pathologic
      changes and to obtain the best possible visualresults in some cases.

PMID- 16883943
TI  - [Outcomes of surgical management in adults with unilateral superior oblique
      muscle palsy].
AB  - PURPOSE: The purpose of this study was to determine the outcomes of surgical
      management in adult patients with unilateral superior oblique muscle palsy.
      MATERIAL AND METHODS: A retrospective review of 82 patients who underwent
      surgical correction at the Department of Strabismology, Cracow Eye Hospital over
      a 20 years period (1982-2003) was done. The patients were divided into 2 groups:
      congenital (group I) and acquired (group II) of superior oblique muscle palsy.
      Group I consisted of 43, group II of 39 patients. The mean age at surgery was 34
      years in the congenital and 38 years in the acquired group. Preoperative and
      postoperative vertical deviation and excycloduction was measured in diagnostic
      positions of gaze using a major synoptoscope. RESULTS: There were a total of 97
      operations: inferior oblique muscle recession was performed in 61 patients,
      superior oblique muscle tuck in 33, contralateral inferior rectus muscle
      recession in 1 patient, superior rectus muscle recession in 1 patient and
      inferior rectus muscle resection in 1 patient. 83% of patients underwent muscle
      surgery once, 16% were operated twice and 1 patient was operated three times. An
      average of 1.1 surgeries were performed per patient in the congenital group and
      1.2 in the acquired group. In both groups, in all diagnostic positions of gaze,
      the mean preoperative vertical deviation in patients operated twice was found to
      be significantly greater than in patients operated once. There was no such
      relationship found for excyclotorsion. In both groups high and statistically
      significant correlation was found between the amount of vertical deviation and
      excyclotorsion before treatment and their reduction in the inferior oblique
      muscle recession group. For the superior oblique muscle tuck, such a relationship
      was found only in the acquired group. For both groups (congenital and acquired)
      recession of the inferior oblique muscle was found to be more effective than
      superior oblique muscle tuck in the reduction of vertical deviation and
      excyclotorsion for primary position, downward gaze and downward gaze in
      adduction. Only in upward gaze in adduction the superior oblique muscle tuck,
      proved to be more effective than inferior oblique muscle recession.
      Hypercorrection (vertical and torsional) was found only in the upper field of
      binocular gaze. Postoperative Brown's syndrome was found to be more frequent
      after a superior oblique muscle tuck than after recession of the inferior oblique
      muscle. The risk of postoperative Brown's syndrome after the superior oblique
      muscle tuck was particularly high in the congenital group. CONCLUSIONS: Recession
      of the inferior oblique muscle was found to be not only more effective but also
      safer than superior oblique muscle tuck.

PMID- 16883942
TI  - [Results of combined chemoreduction and local treatment for intraocular
      retinoblastoma].
AB  - PURPOSE: Of this study was to evaluate the results of combined treatment for
      intraocular retinoblastoma. MATERIALS AND METHODS: We examined 23 children (32
      eyes), 14 with unilateral and 9 with bilateral disease. 53% of eyes had the stage
      V of the disease, according to Reese-Ellsworth. RESULTS: In I-III group according
      to R-E, it was possible to save more than 90% of eyes. In group IV-V we saved 20%
      of eyes. CONCLUSIONS: Chemoreduction combined with local treatment is an optimal
      method of treatment for retinoblastoma, especially in I-III group.

PMID- 16883944
TI  - [Results of laser photocoagulation in patients with diabetic retinopathy
      developed as a complication of diabetes type 2].
AB  - PURPOSE: Laser photocoagulation is a widely used method of treatment of diabetic
      retinopathy. The purpose of the work was to analyze the results of laser
      photocoagulation of the retina in patients with diabetic retinopathy, as a result
      of diabetes type 2. MATERIAL AND METHODS: The examined group consisted of 129
      patients with diabetes type 2, treated in the Regional Centre of Diabetology and
      Metabolic Diseases in Lodz, who underwent laser photocoagulations as a treatment
      of diabetic retinopathy. Patients age were 30 to 82 years old (mean age 61), had
      been treated for diabetes from 1 year to 47 years (mean 17 years). Laser
      photocoagulations were performed in 258 eyes. The evaluation of results was based
      on 6 months follow-up examinations after laser treatment and comprised functional
      results and condition of the eye fundus. RESULTS: In the examined groups simple
      non proliferative diabetic retinopathy was recognized in 36 eyes (13.95%),
      preproliferative retinopathy in 158 eyes (61.24%) and proliferative retinopathy
      in 64 eyes (24.8%). Focal photocoagulations were performed in 103 eyes.
      Improvement in visual acuity was noted in 82 eyes (79.61%) and stabilization or
      improvement in the state of the eye fundus in 92 eyes (89.32%). "Grid"
      photocoagulation was carried out in 73 eyes, improvement in visual acuity was
      noted in 53 eyes (72.60%) and stabilization or improvement in the state of the
      eye fundus in 58 eyes (79.45%). Panretinal photocoagulation was performed in 82
      eyes. Improvement or stabilization of visual acuity was observed in 46 eyes
      (46.10%) and stabilization of state of the eye fundus in 54 eyes (65.85%). In
      cases of patients with non proliferative diabetic retinopathy stabilization of
      visual acuity was observed in 86.11% of eyes and stabilization of the eye fundus
      in 94.44% of eyes. In patients with preproliferative diabetic retinopathy
      stabilization of visual acuity was found in 71.52% of eyes and stabilization of
      state of the eye fundus in 80.38% of eyes. In cases of patients with
      proliferative retinopathy the percentages amounted to 57.81% and 67.19%,
      respectively. CONCLUSIONS: The best functional results of laser
      photocoagulations, as well as stabilization of state of the eye fundus were
      achieved in patients with non proliferative retinopathy and after focal laser
      photocoagulations. The least favourable results were achieved in patients with
      proliferative diabetic retinopathy and in patients after panretinal
      photocoagulations. It probably results from the intensity of retinal lesions,
      which were an indication for these types of photocoagulations. The achieved
      improvement was greater regarding anatomical results, when compared to functional
      results. In order, to prevent the development of diabetic lesions in the eye
      fundus, it is necessary to carry out regular ophthalmologic check-ups, to qualify
      patients for laser photocoagulations, as early as possible.

PMID- 16883945
TI  - [Retinal changes in patients with familial adenomatous polyposis].
AB  - PURPOSE: The aim of study was to evaluate retinal changes in patients diagnosed
      with familial adenomatous polyposis (FAP) and in patients with family history of
      FAP. MATERIAL AND METHODS: The study was conducted on 51 patients diagnosed with
      FAP and 35 subjects with family history of FAP. RESULTS: In 44 patients diagnosed
      with FAP (86.2%), typical pigmentation of fundus lesions were observed, in 1
      patient atypical fundus changes were evident. However, in the group of patients
      with family history of FAP, the presence of typical fundus lesions was observed
      in 9 patients (25.7%). In the period of at least 6 month observation, no changes
      in fundus lesions were present in both groups. CONCLUSIONS: The occurrence of
      retinal changes typical for FAP, especially in patients with family history of
      the disease, should imply the higher risk of FAP.

PMID- 16883946
TI  - [Assessment of tears secretion after refractive surgery].
AB  - PURPOSE: One of the complications of the corneal refractive surgery is a
      transient disturbance in tears secretion, which can lead to the dry eye syndrome.
      The aim of the study was to evaluate the tears secretion in patients after PRK,
      LASEK and LASIK surgery for myopia. MATERIAL AND METHODS: We examined 115 eyes of
      69 patients (46 woman and 23 men), mean age 30.82, with myopia and myopic
      astigmatism, treated with three different refractive procedures. The patients
      included in this study were divided into three groups: Group I: 35 eyes of 22
      patients (15 woman and 7 men) treated with PRK. The mean spherical equivalent of
      the refractive error was -4.18 dioptres (from -8.75 to -2.0). Group II: 41 eyes
      of 23 patients (13 woman and 10 men) treated with LASEK. The mean spherical
      equivalent of the refractive error was -5.73 dioptres (from -12.0 to -2.75).
      Group III: 39 eyes of 24 patients (18 woman and 6 men) treated with LASIK. The
      mean spherical equivalent of the refractive error was -7.49 dioptres (from -10.75
      to -3.75). In this study the amount of tears secreted was analyzed on the base of
      Schirmer I test, performed before and after surgery. Test was always performed in
      the same room, in the morning hours (before noon), with constant temperature and
      air humidity values. RESULTS: In the PRK group the mean value of Schirmer I test
      was 20.91 mm before surgery. 14 days after surgery the mean value decreased to
      14.09 mm, 1 month after surgery to 11.66 mm. Then increase in tears secretion was
      observed: 2 months after surgery the mean value of Schirmer I test was 13.94 mm,
      3 months after surgery 15.23 mm, and 6 months after surgery 17.4 mm. In the LASEK
      group the mean value of Schirmer I test was 20.39 mm before surgery. 14 days
      after surgery the mean value decreased to 15.78 mm, 1 month after surgery to
      13.05 mm. Two months after surgery the mean value of Schirmer I test was 15.24
      mm, 3 months after surgery 16.17 mm, and 6 months after surgery 18.15 mm. In the
      LASIK group the mean value of Schirmer I test was 20.72 mm before surgery. 14
      days after surgery the mean value decreased to 12.97 mm, 1 month after surgery to
      5 mm. 2 months after surgery mean value of Schirmer I test was 12.79 mm, 3 months
      after surgery 15.05 mm, and 6 months after surgery 17.82 mm. CONCLUSIONS: Corneal
      refractive surgery causes transient reduction of tears secretion, especially
      during the first three postoperative months. The tears secretion was reduced most
      significantly in the LASIK group. In patients treated with PRK and LASEK tears
      secretion during the postoperative period was comparable with slightly better
      secretion in the LASEK patients.

PMID- 16883947
TI  - [Early intubation of lacrimal duct in traumatic and operative lower eyelid loss
      and medial canthal region defects, with simultaneous reconstruction dressed by
      application of self constructed battlefield ophthalmic dressing].
AB  - The treatment of acquired, imperfect drainage of tears through the lacrimal duct
      system in the situation of medial canthal region defect (operative or traumatic),
      is an important part of clinical ophthalmology and reconstructive surgery. The
      multidisciplinary approach to the reconstruction of all soft tissues with use of
      early prosthetic reconstruction and lower canalicular intubation by use of
      silicone tube or simple nylon thread, is the theme of the paper. The lacrimal
      duct repair should be performed on primarily, as well as coverage or
      reconstruction of skin defect. The authors compared the efficiency of simple
      lower canalicular intubation with use of normal surgical thread or silicone tube,
      with immediate medial canthal region defect plastic reconstruction.
      Simultaneously, the original self-constructed special battlefield ocular dressing
      was tested in the analyzed cases, to determine whether it is the suitable or not,
      in the procedure. The results were estimated on the base of clinical criteria:
      degree of epiphora after 6/12 weeks (subjective and evaluated accordingly to Munk
      score), early lacrimal obstruction/stenosis, comfort/discomfort of patient, and
      utility of the military dressing (bad/good/very good). The proposed own method of
      simple use of nylon thread seems to be useful, particularly in traumatic damage
      of lower canaliculus associated with multilayer medial canthus soft tissues
      defects and facial bone structures impairment. In analyzed material, it was more
      comfortable for patients than silicone intubation and may be utilize in
      definitive reconstruction, as well as in temporary splinting of lacrimal system
      and creation of artificial lacrimal drainage through the lower canaliculus. It is
      useful at the battlefield conditions. The battlefield ocular dressing tested on
      was very high evaluated in traumatic cases and considered as good in neoplastic
      patients.

PMID- 16883948
TI  - [Pseudoexfoliation syndrome--etiopatogenesis and clinical course].
AB  - Pseudoexfoliation syndrome is an ocular manifestation of a systemic elastosis.
      Exact etiology of this condition remains unknown. The basic pathogenetic concept
      of PEX is a pathological process of the extracellular matrix, characterized by
      the excessive production of an abnormal extracellular material which aggregates
      and accumulates and is not degraded in vivo. This material is produced primarily
      by the non pigmented epithelium of the ciliary body, the posterior iris pigment
      epithelium, and the preequatorial lens epithelium, while the corneal endothelium,
      trabecular cells, and vascular endothelia and smooth muscle cells of the iris
      have also been implicated. PEX material has a complex glycoprotein/proteoglycan,
      composition containing glycosaminoglycans (heparan sulfate, chondroitin sulfate,
      dermatan sulfate, hyaluronic acid). The prevailing presence of elastic fiber
      epitopes, mainly elastic microfibrillar components (elastin, vitronectin, amyloid
      P, fibrillin-1, LTBP-1), has led to the current theory explaining PEX as a type
      of elastosis, affecting especially elastic microfibrils. Ocular deposition of
      pseudoexfoliation material can lead to many complications in intraocular surgery
      like increased risk of zonular dehiscence, capsular rupture, vitreous loss during
      cataract extraction. Special attention is required before, during and after
      surgery.

PMID- 16883949
TI  - [Proliferative vitreoretinopathy--selected issues concerning morphology and
      pathophysiology].
AB  - Based on the literature review the article presents state of the art knowledge on
      creation, structure and pathophysiology of membranes occurring in PVR.
      Additionally selected clinical risk factors are discussed.

PMID- 16883950
TI  - [Lens dislocation in children].
AB  - Ectopia lentis in children continues to be a diagnostic and therapeutic challenge
      for ophthalmologists. It can occur in isolation, in association with other ocular
      disorders or as part of systemic disorder. Marfan's syndrom and homocystinuria
      are the most frequent cause of heritable ectopia lentis. The authors describe
      ocular findings and clinical symptoms diseases with ectopia lentis. Differential
      diagnostic and treatment methods are discussed.

PMID- 16883951
TI  - [Electrophysiological tests in early and differential diagnosis of some
      hereditary retinal and optic nerve diseases].
AB  - PURPOSE: The goal of our study was to determine the value of electrophysiological
      tests in early and differential diagnosis of some hereditary retinal and optic
      nerve diseases. MATERIAL AND METHODS: Review article on the basis of own
      experiences and results of another authors concerning to EOG, ERG, PERG, MfERG
      and VEP tests in evaluation of hereditary, stationary and progressive retinal
      diseases, as well as optic nerve diseases. RESULTS: Electrophysiological tests
      can be abnormal even in patients without fundus changes seen in routine
      ophthalmological examination. CONCLUSIONS: Electrophysiological tests are useful
      in early and differential diagnosis of some hereditary retinal and optic nerve
      diseases. General ophthalmologists should remember about its application,
      especially in difficult diagnostic cases.

PMID- 16883952
TI  - [Biosynthesis of nitric oxide and its function in organism].
AB  - Nitric oxide (NO) is a gas with diverse biological activities produced from L
      arginine by nitric oxide synthetase (NOS). This article provides a short overview
      of the basic function of NO which takes part in smooth muscle relaxation,
      neurotransmission, modulation of inflammation in a number of tissues and
      pathological conditions. The discovery of these new physiological and
      pathological pathways allows for better understanding of many complex processes.
      It opens a new field for better treatment of many diseases.

PMID- 16883953
TI  - [The role of nitric oxide in physiology and pathogenesis of ocular diseases].
AB  - Nitric oxide (NO) is a gas with diverse biological activities produced from
      arginine by nitric oxide synthetase (NOS). The loss of retinal ganglion cells is
      a hallmark of many ophthalmic diseases including glaucoma, retinal ischemia due
      to central artery occlusion and anterior ischemic optic neuropathy. It may well
      be significant in optic neuritis, optic nerve, trauma and AIDS. NO appears to be
      involved in the regulation of intraocular pressure, in the modulation of ocular
      blood flow and in apoptosis. This article gives a short and simplified overview
      of the biochemistry of NO and its role in physiology and pathogenesis of ocular
      diseases.

PMID- 16883954
TI  - [Dissociated vertical deviation (DVD)-- etiology, symptoms, treatment].
AB  - The authors present etiology, diagnostic difficulties, clinical features and
      treatment of dissociated vertical deviation.

PMID- 16883955
TI  - [Role of the organ of vision in the course of developmental dyslexia].
AB  - PURPOSE: To present and describe the role of the organ of vision in the course of
      developmental dyslexia. MATERIAL AND METHODS: A comprehensive review of
      contemporary literature about the etiopathogenesis and the clinical symptoms of
      dyslexia was conducted. RESULTS: Developmental dyslexia in other words is the
      specific difficulty of a person with reading and writing caused by a deficit in
      the development of perceptive and motoric functions as well as the coordination
      of these functions. The etiopathogenesis of dyslexia is not definitely
      determined. Currently developmental dyslexia is thought to be determined by
      environmental and genetic factors. In accessible literature it is noted that a
      total of 5-17.5% of all people is effected by dyslexia. It is widely regarded
      that 63% of all sufferers of dyslexia develop the auditory type of dyslexia with
      an additional 9% having the visual type of dyslexia, while the rest develop a
      mixed type. The basis of visual dyslexia lies in the disorder of visual
      perception linked to the disorders of visual and motoric coordination as well as
      visual and spatial integration. People with developmental dyslexia tend to evolve
      numerous changes in the magnocellular pathway, eyeball movements, accommodation
      as well as binocular vision.

PMID- 16883956
TI  - [Spectral optical coherence tomography (SOCT) in diagnosis of diseases of macula-
      own results].
AB  - In this paper general information about spectral optical coherent tomography
      (SOCT) is presented. SOCT was used in diagnosis of choroidal neovascularization
      (16 eyes), central serous chorioretinopathy (4 eyes), macular hole (8 eyes),
      epiretinal membrane (3 eyes) and familial dominant drusen (2 eyes). In all cases
      SOCT examination revealed new data useful in detailed diagnosis. SOCT is a
      valuable complementary examination to fluorescein and indocianine green
      angiography in diagnosis of macula diseases.

PMID- 16883957
TI  - [The application of the confocal microscopy for the diagnosis of corneal
      inflammation].
AB  - In the course of keratitis, the early diagnosis is very important to start with
      the effective treatment. Clinical state and slit lamp biomicroscopic examination
      not always allows to establish etiologic factor. In this paper, usefulness of the
      confocal microscopy in vivo examination to diagnose cases of not clear etiology
      in corneal inflammation, was presented. Authors presented the correlation between
      the clinical signs and the confocal images basis in five examined patients.

PMID- 16883958
TI  - [Anterior ischemic optic neuropathy associated with giant cell arteritis. Case
      report].
AB  - Giant cell arteritis is a systemic vasculitis that affects large- and medium
      sized arteries. The most common ophthalmic manifestation of this disease is
      anterior ischemic optic neuropathy, leading to acute, painless visual loss in one
      or both eyes. It is caused by ischemia of the optic nerve head, which is mainly
      supplied by the short posterior ciliary arteries. Early diagnosis is the key to
      correct management and prevention of visual loss in the second eye. The treatment
      of choice for arteritic ischemic optic neuropathy is high dose of systemic
      corticosteroids. Only such treatment may prevent blindness. The authors presented
      a case of a 62 years man with anterior ischemic neuropathy in one eye, which was
      diagnosed as arteritic form caused by giant cell arteritis. The correct diagnosis
      was based on typical clinical signs of ischemic changes in the optic nerve head
      and diagnostic criteria for giant cell arteritis, advocated by American College
      of Rheumatologists.

PMID- 16883959
TI  - [Adult-onset vitelliform macular dystrophy (AVMD)--case report].
AB  - PURPOSE: Adult onset vitelliform macular dystrophy (AVMD) was first reported by
      Gass in 1974. This paper presents rare case of AVMD, in 3 years course of
      observation. MATERIAL AND METHODS: Visual acuity of R.E. was 0.1 with
      metamorphopsias in Amsler-test., of L.E. was 1.0 sc. The metamorphopsias in LE
      were first noticed 3 years later. In ophthalmoscopy in LE typical a vitelliform
      like macular lesion was seen, in RE faded vitelliform changes and the RPE atrophy
      around it. FA of RE showed typical hypofluorescent spot in the center of the
      macula with small hyperfluorescent spots around it, called corona sign. The same
      changes in FA of the LE were first noticed 3 years later. The OCT showed central
      thickening in the reflective band representing RPE in both eyes. The ERG and EOG
      results were normal. CONCLUSIONS: The ophthalmoscopic appearance of the AVMD is
      very similar to that in Best's disease. In our case the correlation between
      appearance of metamorphoses and changes in AF was presented.

PMID- 16883960
TI  - Visual symptoms in McCune-Albright syndrome--case report.
AB  - McCune-Albright syndrome is a rare complex genetic disorder. It is diagnosed on
      the basis of bone lesions--fibrous dysplasia, accompanied by at least one
      additional symptom: hyperactivity of endocrine glands or cafe au lait skin spots.
      We present symptoms, clinical picture and diagnostic procedure in a 15-year-old
      patient with visual disorders in the course of McCune-Albright syndrome. The
      ophthalmic disturbances were the part of described syndrome. The active behaviour
      of the ophthalmologist in multidisciplinary diagnostic procedure led to the
      establishment of a proper diagnosis and optimal treatment.

PMID- 16883961
TI  - [Idiopathic myositis--a case report].
AB  - We present a case of idiopathic myositis of medial rectus muscle in 13-year old
      boy. Patient was admitted to pediatric ward due to severe headache and
      periorbital edema. In opthalmological examination serious limitation of adduction
      together with pain on the eye movements, was found. MRI of the orbit revealed
      significant enlargement of medial rectus muscle of the RE. Laboratory tests
      excluded thyroid dysfunction. Systemic steroid therapy was induced. Symptoms
      regressed 10 days after beginning of treatment.

PMID- 16883962
TI  - Test for stem cells--and for Senator Talent.

PMID- 16883963
TI  - Rebuilding the foundations--constantly.

PMID- 16883964
TI  - Hygiene behaviour of adolescents in the Pacific: associations with socio
      demographic, health behaviour and school environment.
AB  - This study presents findings on health-related hygiene behaviours of 9,013
      adolescents from Vanuatu, Tonga and Pohnpei in the Federal States of Micronesia
      as part of the Health Behaviour of Pacific Youth Life surveys. We examined the
      prevalence of and relationship between tooth brushing, hand washing before
      eating, hand washing after toileting and a range of psychosocial factors such as
      sociodemographic charac-teristics, health behaviour and school affiliation. The
      results showed that patterns of prevalence and relationships were consistent for
      all countries, with weaker associations observed in Pohnpei. In general,
      adolescents reported moderate levels of optimal hygiene practice. Girls reported
      significantly more frequent optimal hygiene practice than boys. Logistic
      regression analysis confirmed that frequent hygiene behaviours were significantly
      associated with gender, parental occupations and high levels of school
      affiliation. These findings suggest the need to consider psycho-social and
      economic factors when examining potential influences on hygiene behaviour to
      ensure effective interventions.

PMID- 16883965
TI  - Nutritional status of adults among Munda and Pod populations in a peri urban area
      of Kolkata City, India.
AB  - A cross sectional study on 387 Munda and 317 Pod adult males and females was
      conducted in the peri urban region of Kolkata city, India, to assess their health
      status. Chronic Energy Deficiency (CED) was calculated from the Body Mass Index
      (BMI) and seven anthropometric measurements were considered for this study.
      Significantly higher CED was observed among the Munda males and females. Higher
      percentage of CED was noticed among the females than the male Munda. Linear
      regression coefficient (b +/- standard error) of BMI on age and anthropometric
      measurements revealed significant decrease in BMI with increase in age among
      Munda males and females as well as Pod females. All other measurements more or
      less increased with increase in BMI. Thus, both intra- and inter-ethnic health
      differences were observed between and among the two socioeconomically backward
      populations. Higher gender differentials were found among the Munda and this
      needs an immediate attention of the government to overcome the health inequality
      at regional level.

PMID- 16883966
TI  - Effect of B vitamins-fortified foods on primary school children in Beijing.
AB  - The objective of this study is to investigate the effect of B vitamins-fortified
      foods on primary school children. A controlled trial was conducted in 101 normal
      primary school children aged 9-11 years. They were randomly assigned to
      supplemental control group (S-control, n=36), riboflavin supplementation group
      (+riboflavin 0.625 mg/day, n=32), and B vitamin compound supplementation group
      (+riboflavin 0.625 mg/day, +thiamin 0.512 mg/day, +nicotinic acid 0.365 mg/day,
      +folic acid 0.13 mg/day, n=33) based on school classes. Urinary riboflavin
      excretion and erythrocyte glutathione reductase activity coefficient (EGRAC)
      along with erythrocyte transketolase activity (ETKA) were used to evaluate B
      vitamin levels in the children. AYP index, an index reflecting the brain
      performance ability, was chosen to assess the children's study abilities. Health
      education was carried out to help children and their parents adopt scientific
      dietary concepts. The urinary riboflavin excretion was higher in two
      supplementation groups (435.24 +/- 153.3 microg/g creatinine, 374.6 +/- 144.6
      microg/g creatinine) than in S-control group (235.1 +/- 86.2 microg/g
      creatinine). Average values of EGRAC were lower in two supplementation groups
      (0.90 +/- 0.11, 0.80 +/- 0.10) than in S-control group (1.08 +/- 0.25). At the
      same time, the percentage of thiamine pyrophosphate (TPP%) decreased from 63.69
      +/- 28.04 to 42.16 +/- 16.31 in B vitamin compound supplementation group.
      Meanwhile, AYP index increased at the end of the supplementation in two
      supplementation groups. B vitamins supplementation can significantly increase B
      vitamin level in children. Biochemical activities of riboflavin and thiamin can
      improve with the intake of fortified foods. The effect of B vitamin compound
      supplementation is better than that of single riboflavin supplementation when the
      effect of riboflavin's biofunction is considered. In addition, micronutrient
      supplementation appears to assist children's study abilities.

PMID- 16883967
TI  - Childhood diarrhoea in a district in northeast Thailand: incidence and treatment
      choices.
AB  - Diarrhoeal disease is a major public health problem in Thailand. We collected
      information on childhood diarrhoea from a district in northeast Thailand, using
      various approaches which focus on both consumers and providers. The overall
      incidence of diarrhoea in the study area was 2.1 episodes per child per 12
      months, with children under two years of age having a higher rate at 3.0 episodes
      per child per 12 months. Many episodes were not recognized as diarrhoeal episodes
      by caregivers, and treatment was sought in just over half of all episodes.
      Although children received an average of 2.4 items of medicine per episode, there
      was relatively low use of oral rehydration solutions. This study highlights the
      importance of assessing local beliefs when collecting data on diarrhoeal diseases
      in children, and the importance of continuing efforts to improve public health
      education on the management of diarrhoeal diseases.

PMID- 16883968
TI  - Clinical pathways in primary dental care in Malaysia: clinicians' knowledge,
      perceptions and barriers faced.
AB  - The Oral Health Division, Ministry of Health in Malaysia piloted clinical
      pathways (cpath) in primary care in early 2003. This study investigated the
      knowledge, perception of cpaths and barriers faced by the clinicians involved in
      the pilot project. Self-administered questionnaires were sent to the clinicians
      (n=191). Dentists (67.9%) and dental nurses (70.6%) had good overall knowledge of
      cpaths. The majority of the clinicians (67.9% to 95.6%) perceived cpath
      positively in all areas. Only 9.2% of dentists encountered difficulties in using
      cpath forms compared to 28.4% of dental nurses. A higher proportion of dental
      nurses (73.5%) compared to dentists (64.8%) were willing to continue using cpath.
      The majority of dentists (76.7%) and dental nurses (73.1%) were willing to
      participate in future development of cpaths. Overall, there was evidence of
      managerial support for the pilot project. A follow-up of the pilot project was
      somewhat lacking as less than half (43.3%) of the clinicians reported that the
      state coordinator obtained feedback from them. The findings auger well for the
      future implementation of cpath should the Oral Health Division decide to adopt
      cpath routinely in the public oral health care service.

PMID- 16883969
TI  - Evaluation of growth monitoring and promotion (GMP) surveillance system Thailand
      2002.
AB  - This study aims to describe the current practice on growth monitoring and
      promotion (GMP) system in Thailand, identify its constraints and recommend
      appropriate solutions. In the four provinces studied, 80 health centres were
      systematically selected. A total of 80 health officers, 183 health volunteers and
      1,200 caretakers were interviewed and tested for GMP knowledge and practices. One
      fourth of the health officers and half of the volunteers did not understand the
      objectives of the GMP. More than half of the health officers and volunteers did
      not have the skill to weigh properly. About half of the volunteers could not plot
      and explain the growth chart correctly. Only 40% of the caretakers understand the
      growth chart. Documentation of weight on child health card is lacking. We
      recommend adequate trainings and supervisions for health officers and volunteers,
      revised GMP guidelines to enhance integration with other programmes, and a study
      to identify the effectiveness of the GMP.

PMID- 16883970
TI  - The discovery of an unusual cause of indoor radiation pollution.
AB  - The objective of our study is to investigate the reasons why 21 persons suffered
      erythema and other skin changes, and conjunctivae infection after staying in a
      closed room for three hours. A multi-disciplinary case study including
      interviews, building and ventilation inspections, was performed by a
      multidisciplinary team comprising a medical epidemiologist, and an industrial
      hygienist. A self-administered questionnaire was designed to determine the
      magnitude of the health problem of the affected students. By a process of
      investigative elimination, we deduced that the symptoms were caused by accidental
      exposure to ultraviolet C radiation where it was radiated from the germicidal
      ultraviolet lamps. The most common symptoms and signed presented were erythema of
      skin and conjunctivae infection. The erythema of skin and conjunctivae infection
      arose from exposure to ultraviolet C radiation and that safeguards are needed to
      ensure ultraviolet germicidal lamps are not accidentally switched on while a room
      is occupied.

PMID- 16883971
TI  - Establishment of primary care centre for University Malaysia Sabah.
AB  - University Malaysia Sabah campus moved to its present site in Kota Kinabalu,
      Sabah, Malaysia in 1999. A health centre was included in the development plans
      and a two-storey building was constructed to provide the facility for in-patient
      and out-patient care. Clinical catchments include 10,000 students, 1000 academic
      and support staff. The medical faculty was inaugurated in 2003, and it was given
      the responsibility to establish and run the facility for students and staff of
      the University. This paper describes the development of the facility from merely
      a physical structure to what is now a comprehensive, functional outpatient
      service catering for student healthcare, screening, preventive medicine and
      health promotional activities. Currently, these services are provided by the
      faculty members of the Medical School. The incorporation of the medical student
      teaching and collaborative research adds intangible value to the facility. Future
      plans for expansion include specialist medical services.

PMID- 16883973
TI  - [Occupational politics? But of course!].

PMID- 16883972
TI  - [Parent and patient counseling combined with complementary treatment offers in
      gynecology and obstetrics].

PMID- 16883974
TI  - ["I and my fantasy prince, we will improve everything"].

PMID- 16883975
TI  - [Nursing personnel and family--a tense relationship].

PMID- 16883976
TI  - [Possibilities and limits of inpatient pediatric hospice care].

PMID- 16883977
TI  - [DGL (German Society of Pediatric Nursing) e.V. wants to promote parent and
      patient satisfaction and parent integration in pediatric and gynecologic
      clinics].

PMID- 16883978
TI  - [GkinD (Society of Pediatric Clinics and Pediatric Departments in Germany)
      Working Circle--hygiene].

PMID- 16883979
TI  - [Approval of the first vaccine against rotavirus infections in Germany].

PMID- 16883980
TI  - [Parent-child group concept in the first year of life with BISS (meeting-
      information--play--fun)].

PMID- 16883981
TI  - [A good start in life. German Prevention Prize].

PMID- 16883982
TI  - [When is a time limit allowed in work contracts?].

PMID- 16883983
TI  - Ultrastructure and lectin characterization of granular salivary cells from Ixodes
      ricinus females.
AB  - A site-specific glycosylation of salivary glands (SGs) isolated from unfed and
      partially fed Ixodes ricinus females was identified with the use of lectin
      affinity labeling on sections and western blots of SDS-PAGE gels. The results
      revealed that secretory granules of a, b, and c cells of the type II acinus and e
      and f cells of the type III acinus are glycosylated. In partially engorged tick
      SGs, 2 subtypes of c cells were distinguished. The granules of c1 cells contained
      mannose, N-acetyl-D-glucosamine, and sialic acid residues. The granules of b, c2,
      and e cells exhibited complex glycoconjugates rich in mannose, N-acetyl-D
      glucosamine, galactose, N-acetyl-D-galactosamine, and a moderate amount of sialic
      acid. The granules of f cells contained N-acetyl-D-glucosamine and mannose
      moieties. Type III acini surfaces were covered with mannose-specific ConA binding
      sites. Except the granules of salivary cells, sialic acid-specific lectins MAA II
      and SNA strongly bound cuticular structures of alveolar ducts, and weakly with
      the cuticular spiral thread of excretory salivary ducts. The total sialic acid
      level in SG homogenates isolated from partially fed females was determined by the
      thiobarbituric acid method. Sialic acid, which has been found during the
      development of a few insect species, has not been reported in ticks as yet.

PMID- 16883984
TI  - Spermiogenesis and spermatozoon ultrastructure of the cranial digenean
      Troglotrema acutum (Leuckart, 1842).
AB  - Ultrastructure of spermiogenesis and the main characters of the mature
      spermatozoon of Troglotrema acutum are described by means of transmission
      electron microscopy. Specimens were obtained from the nasolacrimal sinuses of an
      American mink (Mustela vison). Spermiogenesis in T. acutum follows the general
      pattern of digeneans. The zone of differentiation is a conical-shaped area
      bordered by cortical microtubules and delimited at its base by a ring of arched
      membranes. This area contains 2 centrioles associated with striated rootlets and
      an intercentriolar body between them. The centrioles develop 2 free flagella that
      grow ortogonally to the median cytoplasmic process. The posterior flagellar
      rotation and proximodistal fusion of the free flagella with the median
      cytoplasmic process originate the spermatozoon. The mature spermatozoon of T.
      acutum is characterized by the presence of 2 axonemes of different lengths
      presenting the 9+'1' trepaxonematan pattern, 2 bundles of parallel cortical
      microtubules, 2 mitochondria, a nucleus, and granules of glycogen. These
      ultrastructural characters are compared with other digenean species previously
      studied and the importance of different spermatological features is discussed.

PMID- 16883985
TI  - Influence of host age and sex on the helminth fauna of the yellow-legged gull
      (Larus michahellis) in Galicia (northwestern Spain).
AB  - We studied the influence of host age and sex on the helminth fauna of 324 Larus
      michahellis captured in different locations in the region of Galicia
      (northwestern Spain). Gulls were grouped into prefledglings, first-year immature
      birds, second- and third-year immature birds, and adults. Second-year, third
      year, and adult birds were grouped by sex. Thirty-six helminth species were
      recorded. Total species richness and mean infracommunity species richness were
      both significantly lower for pre-fledglings than for the other age groups.
      Prevalence increased significantly with age for Brachylecithum microtesticulatum,
      probably reflecting changing feeding habits. Likewise, 8 species
      (Cardiocephaloides longicollis, Microphallus similis, Maritrema gratiosum,
      Gynaecotyla longiintestinata, Brachylecithum microtesticulatum, Himasthla
      elongata, Parorchis acanthus, and Renicola sp.) were absent or had very low
      prevalence in prefledglings. At least 5 of these 8 species are transmitted to
      gulls through ingestion of molluscs or crustaceans, which suggests that these
      types of prey are seldom fed to prefledglings. In Gymnophallus deliciosus, G.
      longiintestinata, and Cosmocephalus obvelatus, mean intensity, and in the latter
      case prevalence, declined with age, suggesting that protective immunity against
      these species increase with age. Only G. deliciosus, Microphallus similis, and G.
      longiintestinata presented significant differences between the sexes.

PMID- 16883986
TI  - Density-dependent topographical specialization in Gyrodactylus anisopharynx
      (Monogenoidea, Gyrodactylidae): boosting transmission or evading competition?
AB  - Viviparous gyrodactylids are remarkable monogenoid ectoparasites, not only
      because of their speciousness, but also due to their unusually wide range of
      hosts. Although many factors have been proposed to determine the location where
      gyrodactylids attach to their hosts, little is known about how their preference
      for specific host body regions changes over the course of infection. In this
      study, we investigate the dynamics of topographical specialization of the
      parasite Gyrodactylus anisopharynx on 2 of its natural freshwater fish hosts
      (Corydoras paleatus and C. ehrhardti), as well as a naive host (C. schwartzi). We
      recorded the spatial location of this parasite from the foundation of the
      infrapopulation to its extinction to assess how topographical specialization is
      affected by host species, the size and the age of the infrapopulation, and the
      possibility of transmission among hosts. Our results indicate that topographical
      specialization is negatively correlated with infrapopulation size and only
      marginally affected by infrapopulation age. Also, the degree of specialization
      was different among host species, but seemed unaffected by the possibility of
      transmission among hosts. Therefore, observed changes in spatial specialization
      of G. anisopharynx do not appear to represent adaptive responses to maximize
      their transmission. Rather, mechanisms such as increased competition and/ or
      local immune responses might cause parasites to occupy less favorable regions of
      the body of their hosts with increasing density.

PMID- 16883987
TI  - Geographic analysis of host use, development, and habitat use of an
      acanthocephalan species, Leptorhynchoides thecatus.
AB  - Leptorhynchoides thecatus (Linton, 1891), an acanthocephalan parasite of
      freshwater fishes, varies in host use, development, and habitat use throughout
      North America. Spatial structure of these characteristics was examined from data
      extracted from the literature. Geographic patterns were inferred from point
      comparisons using correllograms and then tested with Moran's I statistic for
      global and local significance, and visually from regional means within major
      river drainages. Species of Micropterus Lacepede, 1802 (black basses) were common
      hosts in most regions, except the Lower Mississippi and South Atlantic regions
      where species of Lepomis Rafinesque, 1819 (sunfishes) were common hosts.
      Development, described as the proportions of adults relative to cystacanths
      (extraintestinal juveniles), decreased with latitude. Habitat use of L. thecatus
      showed marked geographic patterns. Leptorhynchoides thecatus occurred in the
      intestine of sunfishes in the South Atlantic and Lower Mississippi regions, in
      the ceca in fish of all species included in the study in the Missouri and Texas
      Gulf regions, and both in ceca and intestines in fish of all species in northern
      regions. Leptorhynchoides thecatus showed geographic patterning within the
      variable traits across the range of the species. These patterns may be the result
      of ecological factors or of genetic differences that might indicate L. thecatus
      comprises multiple cryptic species.

PMID- 16883989
TI  - A new diplectanid (Monogenea) genus and species from the gills of the black
      snook, Centropomus nigrescens (Perciformes: Centropomidae) of the Pacific coast
      of Mexico.
AB  - Cornutohaptor nigrescensi n. sp. (Diplectanidae) is described from the gills of
      the black snook, Centropomus nigrescens (Perciformes: Centropomidae) from the
      Pacific coast of Mexico. Cornutohaptor n. gen. is proposed for this new species
      and is characterized by possessing 2 intestinal ceca terminating blindly; a
      germarium looping right intestinal cecum; bilobed testis; 2 seminal vesicles; 7
      pairs of hooks, each with protruding thumb; a grooved ventral bar and coiled male
      copulatory organ (MCO); an accessory piece comprising a "baglike structure" with
      an appendage; dorsal bars associated parallelly to body midline; and no adhesive
      accessory organs on the haptor. Cornutohaptor differs from all confamilial genera
      by including species with anchors with straight and deep root longest, hook pair
      1 reduced in size, MCO with counterclockwise rings, and by the morphology of the
      accessory piece. Cornutohaptor nigrescensi most closely resembles species of
      Murraytrema Price, 1937, Lobotrema Tripathi, 1937, and Murraytrematoides
      Yamaguti, 1958, because of the absence of squamodiscs or lamellodiscs on the
      haptor and tegumental scales on the posterior portion of the body. Cornutohaptor
      differs from these genera in the position and number of haptoral bars (2 bars in
      Lobotrema spp., dorsal bars transversally associated in Murraytrema and
      Murraytrematoides spp.) and in having a coiled MCO (copulatory organ is a
      comparatively straight, poorly sclerotized tube in Murraytrematoides spp.). This
      is the first diplectanid described from a centropomid along the Pacific coast of
      Mexico.

PMID- 16883988
TI  - The occurrence of Lepeophtheirus salmonis and Caligus clemensi (Copepoda:
      Caligidae) on three-spine stickleback Gasterosteus aculeatus in coastal British
      Columbia.
AB  - Infections with sea lice species belonging to Lepeophtheirus and Caligus are
      reported from examinations of 1,309 three-spine sticklebacks collected in coastal
      British Columbia. Over 97% of the 19,960 Lepeophtheirus specimens and nearly 96%
      of the 2,340 Caligus specimens were in the copepodid and chalimus developmental
      stages. The parasites were identified as Lepeophtheirus salmonis and Caligus
      clemensi based on morphology of adult stages. Between 1,763 and 1,766 base pairs
      (bp) of 18S rDNA from adult specimens collected from sticklebacks and salmon
      differed from the GenBank L. salmonis reference sequence by a single bp and were
      distinct from those of 2 other Lepeophtheirus species. A 530-bp region of 18S
      rDNA from chalimus stages of Lepeophtheirus obtained from sticklebacks and salmon
      was identical to that of the L. salmonis reference sequence. The three-spine
      stickleback is a new host record for L. salmonis. The prevalence of L. salmonis
      was 83.6% and that of C. clemensi was 42.8%. The intensities of these infections
      were 18.3 and 4.2, respectively. There was no significant relationship between
      sea lice abundance and stickleback condition factor. Significant spatial and
      temporal variations both in abundance of sea lice and surface seawater salinities
      were measured. The abundance of both sea lice species was lowest in zones in
      which surface seawater salinity was also lowest. Sticklebacks appear to serve as
      temporary hosts, suggesting a role of this host in the epizootiology of L.
      salmonis. The stickleback may be a useful sentinel species with which to monitor
      spatial and temporal changes in the abundance of L. salmonis and C. clemensi.

PMID- 16883991
TI  - Hermaphrodites and supernumerary testicular lobes in Schistosoma mansoni
      (Trematoda: Schistosomatidae) analyzed by brightfield and confocal microscopy.
AB  - Schistosoma mansoni belongs to the dioecious Schistosomatidae. The occasional
      observation of males with rudimentary female characteristics is thought to attest
      the hermaphroditic roots of this parasite. Supernumerary testicular lobes also
      are recurrently seen in this helminth, but their morphology and origin are
      elusive. Here, we investigated the morphology of the supernumerary lobes from 15
      S. mansoni males and similar structures of 2 females in whole mounts by
      brightfield and confocal laser scanning microscopy. The follicles in the females
      were not regarded as testicular lobes, but 1 male had a rudimentary ovary with a
      residual oviduct posterior to the normal set of testicular lobes and was
      considered hermaphroditic. In addition, 6 other males contained supernumerary
      lobes that enclosed fully matured oocytes in variable amounts. In the remaining 8
      males, no female characteristics could be seen, and the lobes showed
      morphologically a more testicular aspect, although this morphology was only
      confirmed in 1 male where spermatozoids were detected. The process underlying the
      expression of supernumerary testes or lobes with oocytes is similar and is, at
      least in part, induced by the host.

PMID- 16883990
TI  - Description and morphometrical variability of a new species of Ligophorus and of
      Ligophorus chabaudi (Monogenea: Dactylogyridae) on Mugil cephalus (Teleostei)
      from the Mediterranean basin.
AB  - A comparative morphological study of specimens of Ligophorus spp. from Mugil
      cephalus in western Mediterranean and the Black Sea localities has been carried
      out, indicating the presence of 2 distinct forms, i.e., Ligophorus chabaudi and
      Ligophorus cephali n. sp. A detailed description of the latter and an up-to-date
      redescription of L. chabaudi are provided. The existence of these 2 morphological
      species was additionally supported by principal component analysis based on 19
      metric characters of 87 specimens arranged in samples defined by parasite species
      and geographical locality. The analysis indicated consistent differences between
      species but not between localities; this pattern was well supported by jackknife
      procedures. Linear discriminant analyses showed that the main metric differences
      between the 2 species were attributable to the lengths of the dorsal and ventral
      bars and to the uncinulus length; use of the first 2 variables was enough to
      allocate all specimens studied to either form. The erection of L. cephali n. sp.
      raises the number of sympatric Mediterranean species of Ligophorus on M. cephalus
      to 3. The known geographical ranges of these species are compared.

PMID- 16883992
TI  - Taxonomic status, redescription, and surface ultrastructure of Ascocotyle
      (Phagicola) pindoramensis n. comb. (Digenea: Heterophyidae).
AB  - Pygidiopsis pindoramensis Travassos, 1928, is redescribed from the holotype and
      specimens obtained from experimental infections of hamsters with metacercariae of
      the naturally infected poeciliids Poecilia vivipara and Phalloptychus januarius
      from Rio de Janeiro, Brazil. Ascocotyle (Phagicola) pindoramensis (Travassos,
      1928) n. comb. is proposed, based on the presence of a solid, tapering muscular
      posterior prolongation of the oral sucker and Ascocotyle (Phagicola)
      mollienisicola (Sogandares-Bernal and Bridgman, 1960) is synonymized with A. (P.)
      pindoramensis because of the identical morphology and measurements of adults and
      metacercariae, similar spectrum of fish intermediate hosts (poeciliids), and the
      same site of infection of the metacercariae. Trematodes designated as Pygidiopsis
      pindoramensis, previously reported from Argentina and Mexico, represent another
      species of Pygidiopsis Looss, 1907, because they possess circumoral spines and
      their oral sucker is devoid of the posterior muscular prolongation. Data on the
      surface morphology of metacercariae and adults of A. (P.) pindoramensis are
      inferred from scanning electron microscopy observations.

PMID- 16883993
TI  - Genetic variation and relationships between isolates and species of the
      entomopathogenic nematode genus Heterorhabditis deciphered through isozyme
      profiles.
AB  - We studied variation in isozyme patterns of 8 metabolic enzymes in 5 species of
      Heterorhabditis (H. bacteriophora, H. indica, H. marelata, H. megidis, and H.
      zealandica) comprising 18 isolates. Isozyme banding patterns of all the 8 enzymes
      were species specific; however, 3 enzymes, i.e., arginine kinase, fumarate
      hydratase, and malate dehydrogenase, displayed distinct patterns among all the 18
      isolates. Phylogenetic analysis of the isozyme patterns produced dendrograms
      depicting a high degree of genetic variation among Heterorhabditis species, with
      the average pairwise distance of 0.2000. Trees constructed using different
      phylogenetic methods showed a relatively close genetic relationship between H.
      megidis and H. zealandica and between H. bacteriophora and H. indica. Also, H.
      bacteriophora HP88 was the most distant species from H. megidis (UK isolate), H.
      marelatus (Oregon isolate), and H. zealandica (X1 isolate) with pairwise distance
      of 0.1957, 0.2228, and 0.2120, respectively. Phylogenetic analysis also revealed
      genetic variation among H. bacteriophora isolates with the average pairwise
      distance of 0.1507. GPS2 and GPS3 were the most closely related isolates with the
      average distance of only 0.0870, followed by GPS1 and GPS2 with average distance
      of 0.1087. In contrast, KMD19 and HP88, OH25, and HP88, and OH25 and Acows
      isolates were the most divergent populations with a pairwise distance of 0.2011
      and 37 character differences. Pairwise distance analysis also revealed that
      genetic divergence among populations of H. bacteriophora is relatively
      independent of geographic distance. Overall, these results demonstrate strong
      subspecies structuring in H. bacteriophora.

PMID- 16883994
TI  - Multilocus microsatellite analysis reveals extensive genetic diversity in
      Neospora caninum.
AB  - Neospora caninum is a world-wide parasite that causes neuromuscular disorders in
      dogs and bovine abortion. Biological diversity among isolates has been proved in
      both in vivo and in vitro studies. In contrast, little is known about the genetic
      diversity of this parasite. Microsatellite sequence analysis constitutes a
      suitable tool that has been used for the genetic analysis of other apicomplexan
      parasites. In this report, we describe the identification and analysis of 13
      microsatellite loci from N. caninum DNA sequences deposited in public databases,
      which were evaluated with the use of 9 isolates grown in vitro. One
      microsatellite was monomorphic, and the remaining 12 loci exhibited 3 to 9
      separate alleles. Multilocus analysis showed that each of the 9 isolates
      investigated here displayed a unique profile and revealed no association between
      the genetic similarity and host or geographic origin. The multilocus analysis
      approach described here might nevertheless provide the powerful tool needed to
      study the genetic complexity of N. caninum and the molecular epidemiology of
      neosporosis.

PMID- 16883995
TI  - Genetic differentiation in eastern European and western Asian populations of the
      liver fluke, Fasciola hepatica, as revealed by mitochondrial nad1 and cox1 genes.
AB  - Partial sequences of mitochondrial genes nad1 (316 bp) and cox1 (429 bp) were
      analyzed to estimate the variability of the liver fluke samples collected in 20
      localities in Russia, Belarus, Ukraine, Bulgaria, Armenia, Azerbaijan, Georgia,
      Turkey, Turkmenistan, and China. The sequences had 4.1% (nad1) and 2.3% (cox1) of
      variable sites, and 13 and 10 haplotypes were identified among nad1 and cox1
      genes, respectively. Spatial analysis of genetic and nucleotide diversity
      indicated little or no structuring of genetic variation between hosts or regions.
      The analysis of distribution of both separate and combined (nad1 + cox1)
      haplotypes revealed the existence of 2 well-defined lineages with 2 main
      haplotypes and a number of shared divergent haplotypes. Our study showed that the
      first lineage included the main N1-C1 haplotype, which was found in Australia,
      China, Georgia, Turkey, Armenia, Azerbaijan, and in all European populations
      (from Russia, Belarus, Ukraine, Bulgaria). The second lineage was found in all
      European populations and in populations from Armenia and Azerbaijan. It was
      suggested that one of the lineages (I) has an Asian origin. The possible source
      of mtDNA variability and associations between lineage divergence of parasite and
      its definitive hosts (cattle and sheep) are discussed.

PMID- 16883996
TI  - Protection against malaria due to innate immunity enhanced by low-protein diet.
AB  - Mice were fed ad libitum with a normal diet (25% protein) or low-protein diets (0
      12.5% protein) for a wk and then infected with a nonlethal or lethal strain of
      Plasmodium yoelii, that is, blood stage infection. The same diet was continued
      until recovery. Mice fed with a normal diet showed severe parasitemia during
      nonlethal infection, but survived the infection. They died within 2 wk in the
      case of lethal infection. However, all mice fed with low-protein diets survived
      without apparent parasitemia (there were small peaks of parasitemia) in cases of
      both nonlethal and lethal strains. These surviving mice were found to have
      acquired potent innate immunity, showing the expansion of NK1.1 -TCRint cells and
      the production of autoantibodies during malarial infection. Severe combined
      immunodeficiency (scid) mice, which lack TCRint cells as well as TCRhigh cells,
      did not survive after malarial infection of lethal strain of P. yoelii, even when
      low-protein diets were given. These results suggest that low-protein diets
      enhanced innate immunity and inversely decreased conventional immunity, and that
      these immunological deviations rendered mice resistant against malaria. The
      present outcome also reminds us of our experience in the field study of malaria,
      in which some inhabitants eventually avoided contracting malaria even after
      apparent malarial infection.

PMID- 16883997
TI  - Cystacanths of Oncicola venezuelensis (Acanthocephala: Oligacanthorhynchidae) in
      Caribbean termites and various paratenic hosts in the U.S. Virgin Islands.
AB  - Cystacanths of Oncicola venezuelensis (Acanthocephala: Oligacanthorhynchidae)
      were discovered in the hemocoel of Caribbean termites (Nasutitermes acajutlae) on
      St. Thomas and St. John islands in the U.S. Virgin Islands. In addition to
      occurring in the insect intermediate host, cystacanths were present in
      subcutaneous nodules of lizards (Anolis cristatellus and Anolis stratulus), in
      the greater omentum of small Indian mongooses (Herpestes auropunctatus), and
      embedded in mesenteries of pearly-eyed thrashers (Margarops fuscatus). These
      vertebrates likely are paratenic hosts, although a definitive host in the Virgin
      Islands is yet to be discovered. Cystacanths from intermediate and paratenic
      hosts agree fully with the original description of proboscis armature, including
      size and shape of hooks and their roots, of the species. Qualitative features of
      developing and growing structures agree with the original description of the
      species, but the sizes are smaller.

PMID- 16883998
TI  - Rearing density and susceptibility of Rana pipiens metamorphs to cercariae of a
      digenetic trematode.
AB  - Cercariae of many digenean trematodes target particular developmental stages of
      their hosts. For some digeneans that are parasites of amphibians, infection
      appears timed to host metamorphosis. The success and timing of metamorphosis is
      itself affected by a number of factors, including host density. We investigated
      the degree to which rearing density of Rana pipiens larvae influenced time to
      metamorphosis and snout-to-vent length and mass at metamorphosis, as well as
      establishment of cercariae of the trematode Manodistomum syntomentera Stafford,
      1905. As expected, individuals metamorphosed later, were smaller, and weighed
      less at metamorphosis if they were reared under intermediate to high densities
      compared with low densities, in experimental outdoor mesocosms. Cercariae
      establishment was higher in smaller metamorphs that took longer to metamorphose
      within the low-density treatment. Additionally, cercariae establishment was lower
      in larvae from the low-density tanks compared with larvae from the intermediate-
      to high-density tanks. However, more tadpoles had failed to metamorphose in the
      intermediate to high rearing densities by the time cercariae were no longer
      available from natural collections of first intermediate hosts, Physa spp. Larval
      amphibians under crowded conditions should experience increased susceptibility to
      trematode establishment in nature, but only if they metamorphose within the time
      period when cercariae are still available.

PMID- 16883999
TI  - Status of Corynosoma (Acanthocephala: Polymorphidae) based on anatomical,
      ecological, and phylogenetic evidence, with the erection of Pseudocorynosoma n.
      gen.
AB  - The possession of genital spines has been considered as a key taxonomic trait to
      differentiate Corynosoma from other genera of the Polymorphidae. However,
      Corynosoma currently consists of 2 groups of species with clear ecological and
      morphological divergences: the "marine" group (with ca. 30 species) infects
      mammals and piscivorous birds in the marine realm, whereas the "freshwater" group
      (with ca. 7 species) infects waterfowl in continental waters. Species from these
      groups differ in shape of body and neck, trunk spination, lemnisci length and
      shape, testes arrangement, and number and shape of cement glands. We tested
      whether species from these 2 groups formed a monophyletic assemblage based on a
      phylogenetic analysis by using 15 morphological characters. We also included
      species of Andracantha, Polymorphus, and Hexaglandula with which potential
      taxonomic conflicts could most likely arise. We obtained 108 equally most
      parsimonious trees of 32 steps, with a consistency index (CI) = 0.59, and a
      retention index (RI) = 0.82. The strict consensus tree indicated that the
      "freshwater" species of Corynosoma form a monophyletic assemblage closely related
      to some species of Polymorphus, whereas the "marine" species of Corynosoma are
      grouped together with Andracantha. Accordingly, Corynosoma is not a monophyletic
      assemblage, and Pseudocorynosoma n. gen. is proposed for the "freshwater" species
      of Corynosoma. This decision was strongly supported by (1) a functional
      comparison of foretrunk muscles between species of Polymophus, Andracantha, and
      Corynosoma; (2) a multivariate morphometric study of proboscis characters and egg
      size; and (3) an analysis of ecological patterns of host-parasite relationships.

PMID- 16884000
TI  - Paracreptotrema blancoi n. gen., n. sp. (Digenea: Plagiorchiformes:
      Allocreadiidae) in the Olomina, Priapichthys annectens (Osteichthyes:
      poeciliidae), from the Area de Conservacion Guanacaste, Costa Rica.
AB  - A new species of allocreadiid digenean is described from Priapichthys annectens
      (Regan) (Osteichthyes: Poeciliidae) in the Area de Conservacion Guanacaste, Costa
      Rica. A new genus, Paracreptotrema, is proposed to accommodate this species as
      well as Fellodistomum mendezi Songandares-Bernal, 1955, which was previously
      described from another poeciliid, Brachyrhaphis episcopi, in Panama.
      Paracreptotrema differs from all other nominal genera of Allocreadiidae by a
      combination of its symmetrical testes, restricted vitellaria, and the lack of
      oral lappets (muscular 'papillae') or other such appendages. Paracreptotrema
      blancoi n. sp. resembles Creptotrema creptotrema Travassos, Artigas and Pereira,
      1928, but differs in lacking ventral oral lappets and in having vitellaria
      extending posteriorly only to the level of the testes. It can be distinguished
      from P. mendezi n. comb. in having a relatively larger and more posteriorly
      placed acetabulum, vitellaria that are more restricted anteriorly, smaller
      testes, and a uterus that does not extend to the posterior end of the body. The
      genus seems to be restricted to poeciliids in Central America.

PMID- 16884001
TI  - Two new species of Xiphocephalus in Eleodes tricostata and Eleodes fusiformis
      (Coleoptera: Tenebrionidae: Eleodini) from the sandhills of western Nebraska.
AB  - Xiphocephalus triplogemmatus n. sp. and Xiphocephalus quadratogemmatus n. sp.
      (Apicomplexa: Eugregarinida) are described from Eleodes tricostata and Eleodes
      fusiformis (Coleoptera: Tenebrionidae), respectively, collected from Keith County
      in the sandhills of western Nebraska. Gamonts can be diagnosed with some
      confidence based on relative size and shape of the deutomerite, but these taxa
      are distinguished by differences in oocyst size, shape, and residuua number.
      Together with Xiphocephalus ellisi from Eleodes opacus in the same region, X.
      triplogemmatus and X. quadratogemmatus form a distinct Nearctic xiphocephalid
      group that is morphologically distinct from groups that occur in the Palearctic,
      Ethiopian, and Oriental regions.

PMID- 16884002
TI  - First record and description of metacercariae of Curtuteria arguinae n. sp.
      (Digenea: Echinostomatidae), parasite of cockles Cerastoderma edule (Mollusca:
      Bivalvia) in Arcachon Bay, France.
AB  - A new Himasthlinae species, Curtuteria arguinae, is described as metacercariae
      from the cockle Cerastoderma edule (L.), collected at Banc d'Arguin (southwestern
      France). These metacercariae encysted preferentially in the mantle and also in
      the foot of cockles. Encysted and chemically excysted metacercariae were studied
      by light microscopy and scanning electron microscopy, respectively. Excysted
      metacercariae were elongated and curved ventrally. They bore a 33-spine
      circumoral collar. Sensory papillae were arranged around the oral sucker and also
      symmetrically along the ventral surface body, from the collar to the acetabulum.
      The dorsal and ventral tegument surfaces were densely packed with similar pointed
      spines. The posterior end of the body was without any spines. Among the
      Curtuteria species described previously, only Curtuteria haematopodis
      Smogorjewskaja and Iskova, 1966 had the same number of circumoral collar spines.
      A 6-yr field survey showed that the cockle population at Banc d'Arguin was
      subjected to a summer infection of C. arguinae. Curtuteria arguinae phenology of
      infection is characterized by interannual variability and seasonality (beginning
      in July-August and maximum in autumn). The first intermediate and final hosts
      remain unknown.

PMID- 16884003
TI  - Restoration of Parafilaroides (Dougherty, 1946) (Nematoda: Metastrongyloidea)
      with description of two new species from pinnipeds of eastern central Pacific.
AB  - The lungs of a northern elephant seal, Mirounga angustirostris (Gill, 1866), and
      Pacific harbor seal, Phoca vitulina richardii (Gray, 1864), from the eastern
      central Pacific, central California coast, were examined for parasites. This
      represents the first thorough description and identification of Parafilaroides
      species from northern elephant seals and Pacific harbor seals on the west coast
      of North America. From this study, 2 new species of Filaroides (Parafilaroides)
      are described, illustrated, and differentiated by shape of vaginal sphincter,
      body morphometrics, and spicule shape from the 4 existing, recognized species in
      the subgenus. In addition, the subgenus Parafilaroides is proposed to be
      reestablished to full generic status in the Filaroididae based on the presence of
      caudal papillae and DNA.

PMID- 16884004
TI  - A new species of Vexillata (Nematoda: Ornithostrongylidae) in Attwater's pocket
      gopher from Texas.
AB  - Vexillata geomyos n. sp. is described as a parasite of Attwater's pocket gopher,
      Geomys attwateri (Geomyidae), from Welder Wildlife Refuge, Texas. The new species
      possesses 12 cuticular ridges; based on this character, it can be distinguished
      from 7 of the 13 species in the genus. From the 6 remaining species, V. geomyos
      can be differentiated because the dorsal ray in 3 of them (V. armandae, V.
      dessetae, and V. vexillata) has 2 short branches arising from main trunk, whereas
      dorsal ray of the new species lacks these branches. In addition, V. geomyos can
      be distinguished from V. brooksi because its spicules are divided at the tip
      (whereas in the new species, spicules are whole). The new species differs from V.
      legallae and V. convoluta in the number and arrangement of cuticular ridges at
      the posterior region of the body.

PMID- 16884005
TI  - A new species of Sciurodendrium (Nematoda: Heligmonellidae) in Sciurus
      aureogaster (Rodentia: Sciuridae) from Morelos, Mexico.
AB  - Sciurodendrium bravohollisae n. sp. (Heligmonellidae) is described as an
      intestinal parasite of 2 squirrels, Sciurus aureogaster Cuvier, 1829, collected
      from Los Robles, Municipio de Tlalnepantla, Morelos State, Mexico. The new
      species differs from all other congeners in possessing a very well-developed and
      sacciform genital cone. This is the seventh species described for the genus and
      the first one recorded in Mexico.

PMID- 16884006
TI  - Molecular characterization of Trichinella genotypes by inter-simple sequence
      repeat polymerase chain reaction (ISSR-PCR).
AB  - A bulk analysis of inter-simple sequence repeat-polymerase chain reaction (ISSR
      PCR) provides a quick, reliable, and highly informative system for DNA banding
      patterns that permit species identification. The present study evaluates the
      applicability of this system to Trichinella species identification. After a
      single amplification carried out on a single larva with the primer 816([CA]nRY)
      under high stringency conditions, which provide high reproducibility, we were
      able to identify by consistent banding patterns 5 sibling species: Trichinella
      spiralis (ISS48), 2 Trichinella britovi isolates (ISS11 and ISS86), Trichinella
      murrelli (ISS35), Trichinella nativa (ISS71), Trichinella nelsoni (ISS29); 3
      additional Trichinella genotypes: T8 (ISS149), T9 (ISS408 and ISS409), and T6
      (ISS34); and the nonencapsulated species Trichinella pseudospiralis (ISS13).
      Moreover, 33 new Trichinella isolates from 2 zoogeographical regions were
      unequivocally identified. All Trichinella isolates have shown an identical
      pattern with those produced by the reference strain. According to these data, we
      have demonstrated that ISSR-PCR is a robust technique that emerges as a useful
      new application for the molecular identification of Trichinella isolates in
      epidemiological studies.

PMID- 16884007
TI  - A new species of Myxidium (Myxosporea: Myxidiidae), from the western chorus frog,
      Pseudacris triseriata triseriata, and Blanchard's cricket frog, Acris crepitans
      blanchardi (Hylidae), from eastern Nebraska: morphology, phylogeny, and critical
      comments on amphibian Myxidium taxonomy.
AB  - During March 2001-April 2004, 164 adult anurans of 6 species (47 Rana blairi, 35
      Rana catesbeiana, 31 Hyla chrysoscelis, 31 Pseudacris triseriata triseriata, 11
      Bufo woodhousii, and 9 Acris crepitans blanchardi) from Pawnee Lake, Lancaster
      County, Nebraska, were surveyed for myxozoan parasites. Of these, 20 of 31 (65%)
      P. triseriata triseriata and 1 of 9 (11%) A. crepitans blanchardi were infected
      with a new species of Myxidium. Myxidium melleni n. sp. (Myxosporea) is described
      from the gallbladder of the western chorus frog, P. triseriata triseriata
      (Hylidae). This is the second species of Myxidium described from North American
      amphibians. Mature plasmodia are disc-shaped or elliptical 691 (400-1,375) x 499
      (230-1,200) x 23 (16-35) microm, polysporic, producing many disporic
      pansporoblasts. The mature spores, 12.3 (12.0-13.5) x 7.6 (7.0-9.0) x 6.6 (6.0
      8.0) microm, containing a single binucleated sporoplasm, are broadly elliptical,
      with 2-5 transverse grooves on each valve, and contain 2 equal polar capsules 5.2
      (4.8-5.5) x 4.2 (3.8-4.5) microm positioned at opposite ends of the spore.
      Myxidium melleni n. sp. is morphologically consistent with other members of
      Myxidium. However, M. melleni n. sp. was phylogenetically distinct from other
      Myxidium species for which DNA sequences are available. Only with improved
      morphological analyses, accompanied by molecular data, and the deposit of type
      specimens, can the ambiguous nature of Myxidium be resolved. Guidelines for
      descriptions of new species of Myxidium are provided.

PMID- 16884008
TI  - A new species of haploporid (Digenea) from the South China Sea.
AB  - Megasolena dongzhaiensis n. sp. was collected from the intestine of Scatophagus
      argus (Linnaeus) (Perciformes: Scatophagidae) from the Dongzhai Bay (110 degrees
      32'-37'E, 19 degrees 51'-20 degrees 1'N), Hainan Province, China. It resembles
      Megasolena acanthuri Machida and Uchida, 1991 in having larger body size, but it
      differs from the latter species in having an oral sucker that is larger, instead
      of smaller, than the acetabulum (sucker length ratio 1:0.456-0.494, and width
      ratio 1:0.61-0.65 in M. dongzhaiensis n. sp., as opposed to 1:1.3-1.7 in M.
      acanthuri). Moreover, the cuticle is spinose rather than aspinose; there is a
      band of circular muscle in the pharynx, and its eggs are smaller instead of
      larger (0.062-0.068 x 0.036-0.039 in M. dongzhaiensis n. sp., compared with 0.087
      0.103 x 0.058-0.072 in M. acanthuri). Finally, the intestinal bifurcation is
      anterior, instead of dorsal, to the acetabulum. It resembles other species of
      Megasolena Linton, 1910 in having oral sucker larger than the acetabulum, and in
      having a circular muscle band in the oral sucker and pharynx, but it differs in
      having a larger body and smaller eggs. This is the first record of a Megasolena
      species from ray-finned fishes as well as in China.

PMID- 16884009
TI  - Biological studies and molecular characterization of a Cryptosporidium isolate
      from ostriches (Struthio camelus).
AB  - There are many reports of cryptosporidial infection in ostriches, but none with
      molecular characterization of the isolates. A study was undertaken for the
      characterization of a Brazilian Cryptosporidium sp. ostrich isolate by using
      molecular phylogenetic analysis of fragments of the 18S ribosomal DNA, heat-shock
      protein (hsp) 70 coding gene, and actin coding gene. Biological studies were
      accomplished by the experimental inoculation of chickens via oral or
      intratracheal routes with fresh ostrich Cryptosporidium sp. oocysts. Molecular
      analysis of nucleotide sequences of the 3 genes by using neighbor-joining and
      parsimony methods grouped the ostrich isolate as a sister taxon of
      Cryptosporidium baileyi and showed that the ostrich isolate is genetically
      distinct from all other known Cryptosporidium species or genotypes. None of the
      inoculated chickens developed infection as determined by mucosal smears,
      histology, and fecal screening for oocysts. Although biological and molecular
      studies indicate that the ostrich Cryptosporidium is a new species, further
      studies regarding morphological, biological, and molecular characteristics of
      other ostrich isolates are required to confirm the species status of the ostrich
      Cryptosporidium.

PMID- 16884010
TI  - A new species of Capillaria (Nematoda: Capillariidae) parasitizing Conger
      orbignianus (Pisces: Congridae) from Argentina.
AB  - Capillaria (Procapillaria) navoneae n. sp. is described from the congrid fish
      Conger orbignianus from waters off Mar del Plata, Argentina (38 degrees 08'S, 57
      degrees 32'W) (prevalence 29.17%, mean intensity +/- SD 6.07 +/- 6.59). The new
      species is assigned to the subgenus Procapillaria Moravec, 1987, despite the
      absence of vulvar appendages in gravid females. Of the 3 species so far known in
      the subgenus, the new one most closely resembles C. (P.) margolisi, from which it
      is distinguished by lacking a medial expansion in the spicule and a slightly
      elevated anterior lip of vulva, and by having a shorter esophagus, a larger
      number of stichocytes, and a shorter tail.

PMID- 16884011
TI  - A new species of Rhabdias from lungs of the wood frog, Rana sylvatica, in North
      America: the last sibling of Rhabdias ranae?
AB  - Rhabdias bakeri n. sp. is described from specimens found in lungs of the wood
      frog, Rana sylvatica, from North Dakota. The new species has previously been
      mistakenly identified as Rhabdias ranae Walton, 1929, a common parasite of the
      leopard frog, Rana pipiens. The new species differs from R. ranae and Rhabdias
      joaquinensis Ingles, 1935 by the shape and size of pseudolabia, shape and size of
      buccal capsule, and wider esophageal bulb. Molecular analysis based on the
      partial sequences of nuclear 18S rDNA gene, complete sequences of internal
      transcribed spacer region, and partial sequences of 28S gene demonstrates clear
      differences between Rhabdias from Ra. sylvatica and Ra. pipiens, and supports the
      status of R. bakeri as a new species.

PMID- 16884012
TI  - Prophylactic administration of ponazuril reduces clinical signs and delays
      seroconversion in horses challenged with Sarcocystis neurona.
AB  - The ability of ponazuril to prevent or limit clinical signs of equine protozoal
      myeloencephalitis (EPM) after infection with Sarcocystis neurona was evaluated.
      Eighteen horses were assigned to 1 of 3 groups: no treatment, 2.5 mg/kg
      ponazuril, or 5.0 mg/kg ponazuril. Horses were administered ponazuril, once per
      day, beginning 7 days before infection (study day 0) and continuing for 28 days
      postinfection. On day 0, horses were stressed by transport and challenged with 1
      million S. neurona sporocysts per horse. Sequential neurologic examinations were
      performed, and serum and cerebrospinal fluid were collected and assayed for
      antibodies to S. neurona. All horses in the control group developed neurologic
      signs, whereas only 71 and 40% of horses in the 2.5 and 5.0 mg/kg ponazuril
      groups, respectively, developed neurologic abnormalities. This was significant at
      P = 0.034 by using Fisher exact test. In addition, seroconversion was decreased
      in the 5.0 mg/kg group compared with the control horses (100 vs. 40%; P = 0.028).
      Horses with neurologic signs were killed, and a post-mortem examination was
      performed. Mild-to-moderate, multifocal signs of neuroinflammation were observed.
      These results confirm that treatment with ponazuril at 5.0 mg/kg minimizes, but
      does not eliminate, infection and clinical signs of EPM in horses.

PMID- 16884013
TI  - Seroprevalence of Toxoplasma gondii in pregnant women and cats in Grenada, West
      Indies.
AB  - Prevalence of antibodies against Toxoplasma gondii was studied in 534 pregnant
      women and 40 domestic cats in Grenada, West Indies. Antibodies (IgG) for T.
      gondii were sought in human sera by an enzyme-linked immunosorbent assay and in
      cat sera by using the modified agglutination test (MAT). Antibodies were found in
      57 % of pregnant women. Seroprevalence increased with age; 51% of 15- to 19-yr
      old women (100 total) had antibodies versus 60% of 20- to 24-yr-old women (127
      total). Antibodies to T. gondii (MAT, 1:25 serum dilution) were found in 35% of
      cats; titers were 1:25 in 7 cats, 1:50 in 4 cats, and 1:500 in 3 cats.
      Epidemiological data suggested that the ingestion of food or water contaminated
      with oocysts was an important mode of transmission of T. gondii to women.

PMID- 16884014
TI  - Evolutionary loss of parasitism by nematodes? Discovery of a free-living filaroid
      nematode.
AB  - A cattle-drinking pool in nature reserve "Zwin" on the Belgian coast contained
      free-living third-stage infective filaroid juveniles. These juveniles clearly
      differ morphologically from all known nematodes. Morphological and molecular
      analyses indicate a position within the Filaroidea. The aberrant biology of this
      nematode, namely, a free-living stage in an aquatic environment, is unknown
      within this superfamily, and the evolution of the parasitic phenotype to a free
      living state is generally thought to be unlikely. However, the obtained placement
      in the small subunit molecular phylogenetic tree suggests that this free-living
      stage is most likely a secondary adaptation. It is reasonable to assert that
      nematodes with complex life cycles still have the genetic potential for a
      reversion from parasitism to a (partial) free-living stage.

PMID- 16884015
TI  - Seroprevalence of Toxoplasma gondii antibodies in humans from rural Western
      Amazon, Brazil.
AB  - Antibodies to Toxoplasma gondii were assayed in sera of 266 humans from 71 farms
      located at Rondonia State, Western Amazon, Brazil, by the modified agglutination
      test (MAT) and the indirect immunofluorescent antibody test (IFAT). Antibodies
      were found in 195 humans (73.3%), with MAT titers of 1:25 in 11, 1:50 in 11,
      1:100 in 16, 1:200 in 27, 1:400 in 38, 1:800 in 37, 1:1,600 in 22, and 1:3,200 or
      higher in 33. From the 71 farms visited, 69 had seropositive humans. Prevalence
      of anti-T. gondii antibodies increased with age of the people (P < 0.05), and no
      difference was observed in the occurrence by gender (P > 0.05). A sanitary
      questionnaire was applied in each farm, and statistical association between the
      serologic status and several variables were analyzed. Home-grown vegetable
      consumption and origin of drinking water (well or river) were the independent
      variables that displayed significant association (P = 0.002 and 0.02,
      respectively). Higher values of occurrence were found in people with consumption
      of home-grown vegetables (76.1%) and people that drink well water (75.4%)
      compared with people that did not consume this type of food (61.9%) and drink
      river water (55.2%). By IFAT (> or = 1:16), 194 of 266 (73%) humans were
      seropositive and there was a good correlation between MAT and IFAT.

PMID- 16884016
TI  - Exposure to Fasciola hepatica miracidia increases the sensitivity of Lymnaea
      (Fossaria) humilis to high and low pH.
AB  - Humidity and temperature have been considered important factors affecting the
      infectivity of Fasciola hepatica to its molluscan host. One hundred and thirty
      laboratory-reared Lymnaea humilis were exposed for 4 hr to the miracidia of F.
      hepatica over a pH range from 4.0 to 10.0, and their rates of survival were
      compared with 130 similarly treated but unexposed control snails. All control
      snails died within 24 hr at pH 4.0, but they showed better survival at pH 5.0
      10.0. Their sensitivity to solutions with high and low pH, however, was increased
      if kept in the presence of F. hepatica miracidia. Snails exposed at pH 5.0 died
      within 24 hr, whereas most other pHs also affected survival such that by day 18
      only those snails exposed at pH 7.2 remained alive. The increased sensitivity of
      the snails to pH could be explained by a damage-mediated release of parasite
      enzymes, because infectivity was highest at pHs associated with the lowest host
      mortality.

PMID- 16884017
TI  - Lack of Sarcocystis neurona antibody response in Virginia opossums (Didelphis
      virginiana) fed Sarcocystis neurona-infected muscle tissue.
AB  - Serum was collected from laboratory-reared Virginia opossums (Didelphis
      virginiana) to determine whether experimentally infected opossums shedding
      Sarcocystis neurona sporocysts develop serum antibodies to S. neurona merozoite
      antigens. Three opossums were fed muscles from nine-banded armadillos (Dasypus
      novemcinctus), and 5 were fed muscles from striped skunks (Mephitis mephitis).
      Serum was also collected from 26 automobile-killed opossums to determine whether
      antibodies to S. neurona were present in these opossums. Serum was analyzed using
      the S. neurona direct agglutination test (SAT). The SAT was modified for use with
      a filter paper collection system. Antibodies to S. neurona were not detected in
      any of the serum samples from opossums, indicating that infection in the opossum
      is localized in the small intestine. Antibodies to S. neurona were detected in
      filter-paper-processed serum samples from 2 armadillos naturally infected with S.
      neurona.

PMID- 16884019
TI  - Acute fatal toxoplasmosis in squirrels (Sciurus carolensis) with bradyzoites in
      visceral tissues.
AB  - Acute toxoplasmosis was diagnosed in 3 gray squirrels (Sciurus carolensis) from
      Louisiana and Pennsylvania. The predominant lesion was multifocal necrosis in
      several organs, especially of the lymph nodes. Numerous Toxoplasma gondii
      tachyzoites were seen in lesions, and the diagnosis was confirmed
      immunohistochemically by reaction with polyclonal T. gondii-specific antibodies.
      Tissue cysts were seen in several organs, including lung alveoli. The presence of
      tissue cysts in alveoli of pet squirrels maybe of public health concern if tissue
      cysts excreted in nasal secretions are swallowed by children.

PMID- 16884018
TI  - Intrahepatic DNA vaccination: unexpected increased resistance against murine
      cysticercosis induced by non-specific enhanced immunity.
AB  - Experimental murine cysticercosis caused by Taenia crassiceps has proved to be a
      useful model with which to test the efficacy of new vaccine candidates and
      delivery systems against pig cysticercosis. A high level of protection against
      murine cysticercosis was previously observed by intramuscular or intradermal DNA
      immunization with the use of the sequence of the recombinant KETc7 antigen cloned
      in pcDNA3 (pTc-sp7). To determine the effect of KETc7 differential expression in
      DNA vaccination, KETc7 was cloned in pGEM 11Zf(+) under the control of the tissue
      specific regulatory promoter phosphoenolpyruvate carboxykinase (pPc-sp7). A high
      level of protection was induced by intrahepatic immunization with pPc-sp7, pTc
      sp7 and the empty vector in the absence of any specific immunity. The empty
      vector pGEM 11Zf(+), the plasmid with the highest content of CpG sequences,
      provided to the most efficient protection. This protection was related to an
      increased number of splenocytes, enhanced nonspecific splenocyte proliferation,
      and intensified intrahepatic INF-gamma production. Overall, intrahepatic plasmid
      CpG-DNA immunization provokes an exacerbated nonspecific immune response that can
      effectively control Taenia crassiceps cysticercosis.

PMID- 16884020
TI  - Hormone levels and infection of Haemoproteus danilewskyi in free-ranging blue
      jays (Cyanocitta cristata).
AB  - Annual spring relapse of blood parasite infections in birds is believed to be the
      result of hormonal changes associated with breeding. As part of a larger study on
      the epizootiology of Haemoproteus danilewskyi in blue jays in south-central
      Florida, we studied the relationship between H. danilewskyi infections and levels
      of luteinizing hormone, prolactin, progesterone, testosterone, estradiol, and
      corticosterone. We found a positive association between intensity of H.
      danilewskyi infection and corticosterone levels in females but not in males. We
      also found no association between infection and levels of prolactin, luteinizing
      hormone, progesterone, testosterone, or estradiol in males or females. In
      addition, we found a positive relationship between levels of corticosterone and
      handling time and between corticosterone and testosterone levels. We suggest a
      possible influence of corticosterone on spring relapse of Haemoproteus spp.
      infections in birds but provide no support for the influence of breeding hormones
      on relapse of these parasites.

PMID- 16884021
TI  - Prevalence of Sarcocystis spp. in two subspecies of caribou (Rangifer tarandus)
      in Newfoundland and Labrador, and foxes (Vulpes vulpes), wolves (Canis lupus),
      and husky dogs (Canis familiaris) as potential definitive hosts.
AB  - A study was conducted to determine the prevalence and geographical distribution
      of Sarcocystis spp. infecting 2 subspecies of caribou (Rangifer tarandus)
      inhabiting Newfoundland and Labrador and its potential definitive hosts. Muscle
      samples of caribou were obtained, primarily from hunters, and feces of red foxes
      (Vulpes vulpes) and wolves (Canis lupus), from trappers, and Husky dogs (Canis
      familiaris), from owners. Histological sections of muscle and flotation methods
      for feces were used for parasitic detection. Sarcocystis sp. infected more than
      50% of barren-ground caribou (R. t. tarandus) from 4 locations in Newfoundland,
      but it was significantly greater in the north, where 99% of woodland caribou (R.
      t. caribou) from Labrador harbored the infection. Sporocysts were observed in 27
      of 32 red foxes from eastern and northern Newfoundland, whereas 15 of 15 wolves
      and 22 of the 38 Husky dogs were infected. Wolves and red foxes probably acquired
      the infection through scavenging, and Husky dogs, from meat they were fed.

PMID- 16884022
TI  - Prevalence of agglutinating antibodies to Toxoplasma gondii in striped skunks
      (Mephitis mephitis), opossums (Didelphis virginiana), and raccoons (Procyon
      lotor) from Connecticut.
AB  - The prevalence of agglutinating antibodies to Toxoplasma gondii was examined in
      striped skunks (Mephitis mephitis), opossums (Didelphis virginiana), and raccoons
      (Procyon lotor) from 8 cities in Connecticut. Ten (42%) of the 24 striped skunks,
      2 of 7 (29%) opossums, and 12 of 12 (100%) raccoons were positive at dilutions of
      1:50 or greater. These results suggest that T. gondii is prevalent in the
      environment, or prey items, or both, of these omnivores in Connecticut.

PMID- 16884023
TI  - A simple molecular technique for identifying marine host fish by sequencing blood
      feeding parasites.
AB  - Gnathiid isopods are common ectoparasites of fish on the Great Barrier Reef,
      Australia. While screening for appropriate markers for phylogenetic studies of
      gnathiids, we found that primers for 12S and 16S rDNA preferentially amplified
      the host fish DNA instead of gnathiid DNA. This amplification occurred even when
      using gnathiids that were not engorged with host blood and adult gnathiids that
      do not feed on fish blood. This method could be used in host-parasite studies to
      identify hosts without having to sample parasites directly from the host (which
      can be costly and requires considerable skill in a marine environment). Target
      ribosomal DNA sequences can be amplified from total DNA extracted from parasites
      that are captured in funnel traps or plankton tows. Sequence data from these can
      be used to identify the hosts that gnathiids were feeding on before capture.

PMID- 16884025
TI  - Urotocus rossittensis (Trematoda: Digenea: Leucochloriidae) in the scarlet-rumped
      tanager, Ramphocelus passerinii, and common bush tanager, Chlorospingus
      ophthalmicus (Passeriformes: Thraupidae), from the Area de Conservacion
      Guanacaste, Costa Rica, with taxonomic revision of the genus and revised key to
      the leuchochloridiid-like Brachylaimoidea.
AB  - Urotocus rossittensis occurs in the bursa Fabricii of the scarlet-rumped tanager,
      Ramphocelus passerinii, and the common bush tanager, Chlorospingus ophthalmicus,
      from the Area de Conservacion Guanacaste, Costa Rica. Morphological examination
      of type material of U. fusiformis and U. kenyensis and Costa Rican specimens
      suggests that U. fusiformis and U. kenyensis are indistinguishable from U.
      rossittensis. Confirmed accounts of Urotocus spp. refer to a single adult
      morphotype whose geographic distribution includes the Palearctic, Africa,
      Nearctic, and northern Neotropics.

PMID- 16884024
TI  - Nourseothricin acetyltransferease: a positive selectable marker for Toxoplasma
      gondii.
AB  - Molecular analysis of parasite genomes will require new molecular genetic tools.
      The nat1 gene of Streptomyces noursei encodes nourseothricin acetyltransferase,
      conferring resistance to the aminoglycoside antibiotic nourseothricin.
      Electroporation of nat1 cassettes into RH or Prugniaud strains of Toxoplasma
      gondii allows for selection of stable nourseothricin-resistant clones.

PMID- 16884026
TI  - Defining parasite communities is a challenge for neutral theory.
AB  - The neutral theory of biodiversity and biogeography is a null model of community
      structure that suggests that it may be possible to explain the richness and
      relative abundance of species through neutral processes of immigration,
      extinction, and speciation, without resort to interactive processes such as
      competition. There have been no attempts to fit neutral models to parasite
      communities to date. The nature of parasite communities, however, challenges the
      basic assumptions of neutral theory. In particular, the spatially dynamic
      relationships between hosts as habitat patches result in immigration rates that
      are in a constant state of flux. In addition, the partial compositional overlap
      of many component communities means that they can affect each other's process
      rates, which violates the zero-sum assumptions of neutral theory. Despite these
      obstacles, many of the patterns that neutral theory seeks to explain are still
      present in parasite communities. Far from being an esoteric special case,
      parasite communities are ubiquitous in nature and, therefore, any attempts to
      produce unified theoretical frameworks should accommodate the characteristics of
      parasite communities, or risk obsolescence.

PMID- 16884027
TI  - [Safety of immunotherapy and skin tests with allergens in children younger than
      five years].
AB  - BACKGROUND: It has been demonstrated that specific immunotherapy, in addition to
      its preventive properties, is an effective and safe therapeutic resource for
      allergic asthma, allergic rhinitis and allergy to insect's venom; however, its
      use in patients younger than five years has been limited due to the risk of
      systemic reactions. OBJECTIVES: To know the frequency and severity of systemic
      reactions in children younger than five years and to know if a greater risk of
      systemic reactions in this group of age is real. PATIENTS AND METHODS: We
      included 239 patients from one to five years of age with diagnosis of allergic
      disease and verified its specific sensitivity with skin tests or RAST and were
      treated with specific immunotherapy. A detailed registry of the application of
      specific immunotherapy was kept from every patient, with special attention to any
      symptom present during the first 30 minutes post application of specific
      immunotherapy or skin test. RESULTS: From January 1996 to June 2005, 6,689
      injections were applied to 239 patients. Only one patient of 36 months of age
      presented with a delayed systemic reactions characterized by generalized hives,
      itching, runny nose, water eyes, 90 minutes post injection. The patient was under
      treatment with Dermatophagoides farinae and pteronissinus (house dust mites) with
      a dose of 1AU for allergic rhinitis. The systemic reactions were treated easily
      and without complications with a single dose of intramuscular epinephrine
      (0.15cc, 1:1000) and oral antihistamine. CONCLUSION: Patients younger than five
      years are not in greater risk of systemic reactions from specific immunotherapy
      or skin tests than the older children or adults and the treatment of those
      systemic reactions does not imply greater difficulty. Because of its preventive
      properties, safety and effectiveness in lowering the severity of symptoms of
      allergic diseases, we concluded that specific immunotherapy should be considered
      at early age, prescribed and administered only by specialist in pediatric allergy
      and in optimal conditions of safety.

PMID- 16884028
TI  - [Impact of the integral allergological treatment on quality of life of patients
      with allergic rhinitis at the University Hospital of Puebla].
AB  - BACKGROUND: In order to determine the impact of allergic rhinitis on the quality
      of life of the patients, standardized and validated questionnaires have been
      developed. The quality of life is the perception of the patient of the functional
      effects of his illness and its therapeutics consequences. OBJECTIVE: To determine
      the modification of index the quality of life on the patients with allergic
      rhinitis attended at the external consultation of the service of allergy and
      clinical immunology of the Hospital Universitario de Puebla when they were
      submitted to integral allergologic treatment. PATIENTS AND METHODS: It was
      carried out a longitudinal, prospective, experimental and prolective study in
      patients of both sexes, older than 18 years with diagnosis of allergic rhinitis,
      a validated and standardized questionnaire was applied to assess the quality of
      life index every 14 days during 6 months. It was measured severity degree at the
      beginning and the end of the study. It was assessed the sample size considering a
      reasonable size of the effect 1 and a variability of 0.8 for usual techniques.
      The severity degree was compared with RIDIT analysis and the mean with variance,
      a value of p smaller than 0.05 was considered significant. RESULTS: Sixteen
      patients were included, 75% were women. The average age was 34.2 years old. When
      the severity degrees were compared it was an average RIDIT of 0.014 with a "z" of
      -5.0 that implicated a value of p < 0.001. The comparison among the initial
      quality of life and the subsequently visits mean was significantly different
      since third visit. CONCLUSION: The integral allergologic treatment modifies the
      quality of life and the severity degree in the patients with allergic rhinitis.

PMID- 16884029
TI  - [Prevalence of chronic urticaria of autoimmune origin at the Regional Hospital
      Adolfo Lopez Mateos].
AB  - BACKGROUND: Chronic urticaria is a common skin disorder characterized by
      recurrent, transitory, itchy wheals with individual lesions lasting less than 24
      hours and affecting patients for six weeks or longer. In adults it has been shown
      that approximately 40% of the patients with chronic urticaria have autoimmune
      urticaria. OBJECTIVE: To determine the prevalence of autoimmune urticaria in
      adults with chronic urticaria. PATIENTS AND METHOD: We studied adult patients
      with chronic urticaria by means of autologous serum skin test (ASST), and by
      antinuclear and antithyroid (antityroglobulin, antiperoxidase) antibodies. We
      compared them with a group matched by sex and age. RESULTS: We included 68
      patients: 34 cases (patients with chronic urticaria) and 34 controls (healthy
      individuals). In the cases we found high levels of TSH (p = 0.003) and positive
      autologous serum skin test (p = 0.04), while in the controls we observed a
      statistically significant difference of the levels of antithyroid antibodies (p =
      0.002). The prevalence of autoantibodies (antithyroid or by autologous serum) was
      present in 55 and 44% of the patients with chronic urticaria. CONCLUSION:
      Autoimmunity is one of the most common causes of chronic urticaria; it may
      explain the pathogenesis in half of the studied cases.

PMID- 16884031
TI  - [Prevalence of seropositividad to antibodies IgG and IgM against Helicobacter
      pylori in the medical residents of the University Hospital of Puebla].
AB  - BACKGROUND: Helicobacter pylori is a gram-negative, curved, microaerophilic,
      oxidase, catalase and urease positive bacillus. It lives in the gastric mucosa,
      and is the main etiological agent of peptic ulcer, and of atrophic and multifocal
      gastritis. It is associated with extraintestinal, vascular, autoimmune and
      cutaneous diseases. The infection by this bacteria causes a chronic inflammatory
      process related with the sensibilization of mast cells, which increases the
      incidence of allergic diseases. OBJECTIVE: To estimate the seropositivity
      prevalence of IgG and IgM antibodies against Helicobacter pylori in medical
      resident personnel. PATIENTS AND METHOD: A transversal, descriptive and
      observational study was carried out in medical residents of the Hospital
      Universitario de Puebla. Serum levels of IgG and IgM antibodies against
      Helicobacter pylori were determined by chemiluminescence. Data were analyzed
      applying descriptive statistics, such as: frequency, central tendency and
      dispersion measures. RESULTS: 57 residents were included, 54.4% were men. The
      mean age was 28.4 (SD 2.9). Seropositivity prevalence of IgG and IgM antibodies
      was 24.6 and 33.3%, respectively. Combined seropositivity prevalence of IgG and
      IgM was of 43.9%. CONCLUSION: Seropositivity prevalence of IgG and IgM antibodies
      against Helicobacter pylori in the medical resident personnel of the Hospital
      Universitario de Puebla was similar to the reported in the general population.
      This estimation might be considered a reference to other epidemiological and
      clinical studies such as those pretending to evaluate and demonstrate the
      relationship between infection by Helicobacter pylori and other entities, even
      allergies.

PMID- 16884030
TI  - [Acute asthma and its costs of care at an emergency service].
AB  - BACKGROUND: The request in the urgency service for attention in acute asthma is
      determined by multiple factors as the medical handling, the constancy and the
      pursuance of the patient in the adequate follow up of the treatment, the climate,
      the food hygienic habits and the allergies. OBJECTIVE: To determine in one year
      period, the frequency, recurrence of medical attention for acute asthma and the
      cost in the hospital urgency service of second level in medical attention.
      MATERIAL AND METHODS: We made an analysis of a secondary study done in 1999 in
      pediatric patients younger than 16 years with diagnosis of acute asthma. RESULTS:
      From 6,912 consultations given in the pediatric emergency area, 2,586 were from
      acute asthma, the half was 5.2 years old patients, the minimal average time a
      patient had to stay in the hospital per month was of 7.36 hours in January and
      the maximum average time was of 22.10 hours in the month of September. Regarding
      the frequency of attendance in the service for a new event, the following
      distribution was found: from two to three 25.72%, from 4 to 6 10.1% and from 7 to
      15 0.96%. The cost of the attention had a total cost of 5'787,494.82 pesos.
      CONCLUSIONS: The frequency of acute asthma was 41.58% and this figure was
      considered high in comparison to similar studies. The clinic evolution and the
      treatment response are related to the age, and, in the study results, the
      patients younger than 3 years had a longer stay in the hospital, also, there was
      an increase of patients in the rainy months. The frequency of patients who
      assisted between 2 or 3 times and the cost was 387,123.00 pesos. That frequency
      may be due to patients did not receive a long-term treatment provision, or
      because of ignorance in the initial rescue treatment, ignorance in the factors
      that raise the sickness, as well as patients not taking their treatment the way
      it was asked by the doctors. These factors increase the cost, which is feasible
      to be modifyied, if the patients and their families get acknowledge on the
      importance of respecting the instructions on the proper way of treating the acute
      asthma, and all the triggering factors of it.

PMID- 16884032
TI  - [Reactions to drugs. A review of literature].
AB  - Adverse drug reactions are originated by immunological and non-immunological
      mechanisms. Estimated incidence is of 6.7%, and the incidence of mortal reactions
      is of 0.32%. In women, skin reaction incidence is 35% higher than in men, and it
      is 20 times higher than presenting contrast medium-related reactions. Allergic
      reaction is classified accordingly to Gell and Coombs criteria. It is unknown the
      pathogenic mechanism of the drug-induced fever. Predictable reaction depends on
      the dose and it is frequently related to the drug. Unpredictable reaction depends
      on the individual and pseudoallergic features of each patient; no immunological
      mechanism is involved. For diagnosis, lymphocyte transformation test measures the
      T cell proliferation to an in vitro drug; furthermore, it is the most sensitive.
      There are just a few options to evaluate and manage those patients. When it is
      impossible to make the exposition test the alternative is to withdraw the drug
      and try another treatment option. If there is no other available drug,
      desensitization must be considered.

PMID- 16884034
TI  - DoH aims to empower patient with three-way partnerships.

PMID- 16884033
TI  - [Reactivation of the scar of BCG vaccination in Kawasaki's disease: clinical case
      and literature review].
AB  - Kawasaki disease is an acute febrile multisystemic vasculitis affecting children
      that can affect the coronary arteries. Routine BCG vaccination in Mexico leads to
      a 99% coverage in infants younger than 1 year. We present a case of Kawasaki
      disease with skin lesions at the site of BCG. Clinicians should be aware of this
      clinical manifestation that could help diagnose atypical or incomplete cases of
      the disease.

PMID- 16884035
TI  - Social enterprise. Good intentions could be disguising a big, bad threat.

PMID- 16884036
TI  - On the case for independence.

PMID- 16884037
TI  - Partnership working. Buddies or barricades?

PMID- 16884039
TI  - Performance. 'We are not looking for blame but improvement'.
AB  - Mersey Regional Ambulance Service was the worst-performing in the country. A
      strategic review recommended a robust approach to performance measurement and
      management. An impressive turnaround was achieved by simplifying management
      systems, rethinking responses to emergency patients and introducing a new
      performance framework.

PMID- 16884038
TI  - Barometer. Public health June 2006.

PMID- 16884041
TI  - Change management. Unlocked potential.

PMID- 16884040
TI  - Clinical management. On living with cancer.

PMID- 16884042
TI  - Law. A matter of life and death.

PMID- 16884043
TI  - Stepping onto raised, laterally compliant structures: a biomechanical study of
      age and gender effects in healthy adults.
AB  - OBJECTIVE: To investigate the effects of gender and age on the kinematics and
      kinetics associated with stepping onto, and balancing on, a raised structure with
      lateral compliance. BACKGROUND: Falls from a stepladder tipping sideways are
      associated with considerable socioeconomic costs. METHOD: Ten young women (YF)
      and 10 young men (YM), aged 23 to 29 years, and 10 older men (OM) aged 66 to 75
      years were asked to step up onto one of two raised structures with increasing
      lateral compliance (C1 and C2), presented in sets of six trials separated by up
      to 12 rigid (C0) structure trials. RESULTS: Structural compliance (C1 or C2)
      significantly affected step duration (p < .05) and lateral weight transfer
      velocity (p < .01). Significant age (p < .001) and gender (p < .05) differences
      were found in step duration and center of mass adjustments: With increasing
      structural compliance, participants required more time (YM: 15%; YF ranged from
      33% to 45%; OM 35%-37%) to complete the step-up movement. CONCLUSION: Increasing
      age and structural compliance were both associated with larger and longer-lasting
      structural oscillations that increase the risk for a lateral fall. APPLICATION:
      Older adults, in particular, should not hurry their movements on raised
      structures. Actual or potential applications of this research include additional
      safety instructions for ladder users and considerations of structural compliance
      for designers and authors of national or international standards for raised
      structures.

PMID- 16884044
TI  - A tactile cockpit instrument supports the control of self-motion during spatial
      disorientation.
AB  - OBJECTIVE: We investigated the effectiveness of a tactile torso display as a
      countermeasure to spatial disorientation (SD) and compared inside-out and outside
      in codings. BACKGROUND: SD is a serious threat to military as well as civilian
      pilots and aircraft. Considerable effort has been put into SD countermeasures
      such as training programs and advanced cockpit displays. Tactile displays have
      been considered a promising technology. METHOD: Twenty-four participants were
      assigned to the two coding groups (12 per group and matched for age and gender).
      We used a rotating chair to build up a state of SD by rotating participants
      around their yaw axis followed by a sudden stop. During the following recovery
      phase a random disturbance signal was added to the chair's orientation.
      Participants actively controlled their orientation and were instructed to
      maintain a stable orientation. RESULTS: Statistical analyses revealed that
      recovery from SD was improved with support of the tactile instrument, but
      tracking performance was reduced. The effects were the same whether the
      instrument was available full time or during the recovery phase only. There were
      no differences between outside-in and inside-out coding. CONCLUSION: The present
      study demonstrates the potential of tactile cockpit instruments in controlling
      SD, even in the presence of strong but misleading self-motion information from
      the vestibular sense. APPLICATION: Actual or potential applications of this
      research include spatial disorientation countermeasures for pilots, divers, and
      astronauts.

PMID- 16884045
TI  - Reading in the dark: effects of age and contrast on reading speed and
      comprehension.
AB  - OBJECTIVE: To explore the effects of contrast reduction on younger and older
      adults' reading behavior and to examine whether readers rely on word
      predictability to compensate for poor contrast. BACKGROUND: Poor contrast can
      degrade text and may influence reading behavior. Readers may compensate for
      visual degradation of text by taking advantage of word predictability. METHOD: In
      Experiment 1, 5 younger and 5 older adults read sentences presented with 10
      levels of contrast. In Experiment 2, 40 younger and 40 older adults read high-,
      medium-, and low-contrast sentences that varied in target word predictability
      (high vs. low). RESULTS: Relative to those of younger adults, older adults'
      reading rates were more slowed by low contrast; comprehension was less influenced
      by contrast (i.e., not significantly). Older adults read high-predictability
      words faster and comprehended them better than low-predictability words,
      significantly so for high- and medium-contrast sentences. Younger adults
      comprehended high-predictability words significantly better than low
      predictability words for high- and low-contrast sentences. CONCLUSION: Low
      contrast was more detrimental for older adults. High-predictability words
      benefited older adults by significantly reducing their reading times and
      benefited all readers by significantly increasing their comprehension.
      APPLICATION: The current findings demonstrate the benefit of adequate contrast
      and word predictability for optimal text design to facilitate both reading times
      and reading comprehension.

PMID- 16884046
TI  - Automation failures on tasks easily performed by operators undermine trust in
      automated aids.
AB  - OBJECTIVE: We tested the hypothesis that automation errors on tasks easily
      performed by humans undermine trust in automation. BACKGROUND: Research has
      revealed that the reliability of imperfect automation is frequently misperceived.
      We examined the manner in which the easiness and type of imperfect automation
      errors affect trust and dependence. METHOD: Participants performed a target
      detection task utilizing an automated aid. In Study 1, the aid missed targets
      either on easy trials (easy miss group) or on difficult trials (difficult miss
      group). In Study 2, we manipulated both easiness and type of error (miss vs.
      false alarm). The aid erred on either difficult trials alone (difficult errors
      group) or on difficult and easy trials (easy miss group; easy false alarm group).
      RESULTS: In both experiments, easy errors led to participants mistrusting and
      disagreeing more with the aid on difficult trials, as compared with those using
      aids that generated only difficult errors. This resulted in a downward shift in
      decision criterion for the former, leading to poorer overall performance. Misses
      and false alarms led to similar effects. CONCLUSION: Automation errors on tasks
      that appear "easy" to the operator severely degrade trust and reliance.
      APPLICATION: Potential applications include the implementation of system design
      solutions that circumvent the negative effects of easy automation errors.

PMID- 16884047
TI  - Learning from technical documents: the role of intermodal referring expressions.
AB  - OBJECTIVE: We investigated the impact of two types of intermodal referring
      expressions on efficiency of instructions for use. BACKGROUND: User manuals for
      software or technical devices such as a video recording system frequently combine
      verbal instructions and illustrations. Much research has shown that the presence
      of an illustration has a beneficial effect on learning. The present study focuses
      on a factor that modulates this beneficial effect. The combination of text and an
      illustration can be effective only if the user integrates the information coming
      from these two media. This integration depends largely on the intermodal
      referential expressions, the function of which is to mark explicitly the
      relations between the text and the illustration. METHOD: In an experiment (N =
      104), we compared the effectiveness of two intermodal referring expressions often
      used in procedural texts: indexes (numbers introduced in the illustrations and in
      the instructions to establish cross-references) and icons (visual representations
      of the components of the device, which are inserted in the verbal instructions).
      RESULTS: The icons condition led to the most efficient use of the device.
      CONCLUSION: This experiment shows that learning from multimedia documents depends
      on the possibility of effectively connecting the verbal instructions to the
      illustration. APPLICATION: Taking into account the ergonomic properties of the
      cross-media referring expressions should allow text designers to improve the
      effectiveness of technical documents.

PMID- 16884048
TI  - Navigation performance with a virtual auditory display: effects of beacon sound,
      capture radius, and practice.
AB  - OBJECTIVE: We examined whether spatialized nonspeech beacons could guide
      navigation and how sound timbre, waypoint capture radius, and practice affect
      performance. BACKGROUND: Auditory displays may assist mobility and wayfinding for
      those with temporary or permanent visual impairment, but they remain
      understudied. Previous systems have used speech-based interfaces. METHOD:
      Participants (108 undergraduates) navigated three maps, guided by one of three
      beacons (pink noise, sonar ping, or 1000-Hz pure tone) spatialized by a virtual
      reality engine. Dependent measures were efficiency of time and path length.
      RESULTS: Overall navigation was very successful, with significant effects of
      practice and capture radius, and interactions with beacon sound. Overshooting and
      subsequent hunting for waypoints was exacerbated for small radius conditions. A
      human-scale capture radius (1.5 m) and sonar-like beacon yielded the optimal
      combination for safety and efficiency. CONCLUSION: The selection of beacon sound
      and capture radius depend on the specific application, including whether speed of
      travel or adherence to path are of primary concern. Extended use affects sound
      preferences and quickly leads to improvements in both speed and accuracy.
      APPLICATION: These findings should lead to improved wayfinding systems for the
      visually impaired as well as for first responders (e.g., firefighters) and
      soldiers.

PMID- 16884049
TI  - Building and testing optimized keyboards for specific text entry.
AB  - OBJECTIVE: We explore how to optimally design systems for information input.
      BACKGROUND: As computers are introduced into ever more devices with new methods
      of inputting information, there is a need for specialized systems that are
      optimally designed for their particular use. METHOD: The study demonstrates how
      to use a model of text entry times to build optimized keyboards for specific sets
      of text. The technique is demonstrated by using Fitts' law to model text entry
      times. Alphabet letters are assigned to keys in a way that minimizes predicted
      entry time for the specified set of text. The predicted entry times are validated
      by an experiment in which two keyboards are optimized for different sets of text.
      RESULTS: Text entry is faster for the keyboard optimized for that text compared
      with the keyboard optimized for the other text. Learning to use the keyboards is
      fairly quick, with significant learning being observed after only one half-hour
      session. CONCLUSION: There is a need and an ability to design specialized
      keyboards for some situations. The study demonstrates that optimization of
      keyboards can decrease text entry times. APPLICATION: This research shows how to
      design optimized keyboards for many different situations. The approach should be
      useful for aviation, medical, industrial, and other specialized situations in
      which normal keyboard designs cannot be used.

PMID- 16884050
TI  - Learning and retention of associations between auditory icons and denotative
      referents: implications for the design of auditory warnings.
AB  - OBJECTIVE: This study examined the way in which the type and preexisting strength
      of association between an auditory icon and a warning event affects the ease with
      which the icon/event pairing can be learned and retained. BACKGROUND: To be
      effective, an auditory warning must be audible, identifiable, interpretable, and
      heeded. Warnings consisting of familiar environmental sounds, or auditory icons,
      have potential to facilitate identification and interpretation. The ease with
      which pairings between auditory icons and warning events can be learned and
      retained is likely to depend on the type and strength of the preexisting
      icon/event association. METHOD: Sixty-three participants each learned eight
      auditory-icon/denotative-referent pairings and attempted to recall them 4 weeks
      later. Three icon/denotative-referent association types (direct, related, and
      unrelated) were employed. Participants rated the strength of the association for
      each pairing on a 7-point scale. RESULTS: The number of errors made while
      learning pairings was greater for unrelated than for either related or direct
      associations, whereas the number of errors made while attempting to recall
      pairings 4 weeks later was greater for unrelated than for related associations
      and for related than for direct associations. Irrespective of association type,
      both learning and retention performance remained at very high levels, provided
      the strength of the association was rated greater than 5. CONCLUSION: This
      suggests that strong preexisting associations are used to facilitate learning and
      retention of icon/denotative-referent pairings. APPLICATION: The practical
      implication of this study is that auditory icons having either direct or strong,
      indirect associations with warning events should be preferred.

PMID- 16884052
TI  - Large displays enhance optical flow cues and narrow the gender gap in 3-D virtual
      navigation.
AB  - OBJECTIVE: Existing reports suggest that males significantly outperform females
      in navigating 3-D virtual environments. Although researchers have recognized that
      this may be attributable to males and females possessing different spatial
      abilities, most work has attempted to reduce the gender gap by providing more
      training for females. In this paper, we explore using large displays to narrow
      the gender gap within these tasks. BACKGROUND: While evaluating various
      interaction techniques, we found that large displays affording wider fields of
      view seemed to improve virtual navigation performance in general and,
      additionally, to narrow the gender gap that existed on standard desktop displays.
      METHOD: We conducted two experiments (32 and 22 participants) exploring the
      individual contributions of display and geometric fields of view to the observed
      effects as well as isolating factors explaining performance increases seen on the
      large displays. RESULTS: We show that wider fields of view on large displays not
      only increase performance of all users on average but also benefit females to
      such a degree as to allow them to perform as well as males do. We further
      demonstrate that these benefits can be attributed to better optical flow cues
      offered by the large displays. CONCLUSION: These findings provide a significant
      contribution, including recommendations for the improved presentation of 3-D
      environments, backed by empirical data demonstrating performance benefits during
      navigation tasks. APPLICATION. Results can be used to design systems that narrow
      the gender gap in domains such as teleoperation and virtual environments for
      entertainment, virtual training, or information visualization.

PMID- 16884051
TI  - Car backlight position and fog density bias observer-car distance estimates and
      time-to-collision judgments.
AB  - OBJECTIVE: A series of experiments assessed biases in perceived distance that
      occur while driving as a function of the backlight position of the car ahead and
      fog density. BACKGROUND: V. Cavallo, M. Colomb, and J. Dore (2001) have shown
      that smaller horizontal backlight separation and fog may result in increased
      estimates of the distance between an observer and a car of which only the
      backlights are visible. They also predicted that raising the height of the car
      backlights would lead to increasing distance estimates. METHOD: Distance
      perception was assessed in both static and dynamic computer-simulated scenarios
      in which the distance estimates were performed using a familiarized analog scale
      or using time-to-collision judgments for both pairs of backlights and single
      backlights. RESULTS: In a series of five experiments, the horizontal separation
      and fog density effects were replicated. In addition, distance estimates were
      consistently larger with higher than with lower vertical backlight positions.
      CONCLUSION: There is reason to believe that biases in distance perception may be
      augmented by car backlight positions and by low-visibility weather conditions.
      APPLICATION: Car designers should take backlight placement seriously. Speed
      dependent car-to-car distance control systems seem desirable to counteract biases
      in distance perception.

PMID- 16884053
TI  - Time-to-collision judgments under realistic driving conditions.
AB  - OBJECTIVE: This study examined perceived time to collision (TTC) with automobile
      drivers under realistic approach, rear-end crash scenario conditions. BACKGROUND:
      TTC refers to the time before impact if prevailing conditions continue. METHOD:
      In this test track study involving 51 drivers ranging from 20 to 70 years old,
      the driver's vision was occluded at either 3.6 or 5.6 s TTC during an in-lane
      approach to a lead vehicle. Drivers provided TTC estimates by pressing a button
      the instant they felt that they would have collided with the vehicle ahead.
      RESULTS: Results indicated that TTC was consistently underestimated. The TTC
      ratio (perceived TTC/actual TTC) increased as driver speed decreased and as
      relative speed increased. These ratios were largely unaffected by age, gender,
      actual TTC, viewing time (1 s vs. continuous), and the presence of an eyes
      forward, mental addition distraction task. CONCLUSION: Overall, these results
      suggest that under these low TTC conditions drivers estimate TTC in a relatively
      uniform fashion and that they are capable of providing this estimate based on a
      brief glimpse to the vehicle ahead. APPLICATION: These results are being used to
      develop an alert timing approach for a forward collision warning system intended
      to assist drivers in avoiding rear-end crashes with the vehicle ahead.

PMID- 16884054
TI  - Presence and quality of navigational landmarks: effect on driver performance and
      implications for design.
AB  - OBJECTIVE: The objective of this study was to investigate the impact of landmark
      information of varying quality within drivers' navigation instructions on driving
      and navigation performance when navigating an unfamiliar route. BACKGROUND:
      Current vehicle navigation systems predominantly use distance-to-turn information
      to enable a driver to locate a forthcoming maneuver. Although it has been
      proposed that the design of driver navigation aids can be improved through the
      incorporation of landmarks as key navigation cues, little research has
      investigated how the quality of the landmark affects driver behavior. METHOD: An
      empirical field trial in a real traffic environment was undertaken with 48
      participants in order to assess the effect of landmark quality on driver behavior
      when navigating an unfamiliar, complex, urban route. RESULTS: The use of good
      landmarks (as opposed to poor landmarks or distance information) as key verbal
      navigation cues resulted in significant improvements in navigation performance,
      driving performance, and driver confidence immediately preceding a turn. The use
      of distance information to locate a turn resulted in significantly more glances
      to the in-vehicle display. CONCLUSIONS: Good landmarks offer significant safety
      and performance benefits to a driver navigating an unfamiliar route. Poor
      landmarks can result in driver performance worse than that obtained using
      distance to turn to locate forthcoming maneuvers. APPLICATION: The design of
      future vehicle navigation systems should not rely on distance-to turn information
      alone to enable a driver to locate forthcoming maneuvers but, rather, should
      incorporate good landmarks within the navigation instructions they present to
      drivers.

PMID- 16884055
TI  - Modeling driver behavior in a cognitive architecture.
AB  - OBJECTIVE: This paper explores the development of a rigorous computational model
      of driver behavior in a cognitive architecture--a computational framework with
      underlying psychological theories that incorporate basic properties and
      limitations of the human system. BACKGROUND: Computational modeling has emerged
      as a powerful tool for studying the complex task of driving, allowing researchers
      to simulate driver behavior and explore the parameters and constraints of this
      behavior. METHOD: An integrated driver model developed in the ACT-R (Adaptive
      Control of Thought-Rational) cognitive architecture is described that focuses on
      the component processes of control, monitoring, and decision making in a
      multilane highway environment. RESULTS: This model accounts for the steering
      profiles, lateral position profiles, and gaze distributions of human drivers
      during lane keeping, curve negotiation, and lane changing. CONCLUSION: The model
      demonstrates how cognitive architectures facilitate understanding of driver
      behavior in the context of general human abilities and constraints and how the
      driving domain benefits cognitive architectures by pushing model development
      toward more complex, realistic tasks. APPLICATION: The model can also serve as a
      core computational engine for practical applications that predict and recognize
      driver behavior and distraction.

PMID- 16884056
TI  - A comparison of the cell phone driver and the drunk driver.
AB  - OBJECTIVE: The objective of this research was to determine the relative
      impairment associated with conversing on a cellular telephone while driving.
      BACKGROUND: Epidemiological evidence suggests that the relative risk of being in
      a traffic accident while using a cell phone is similar to the hazard associated
      with driving with a blood alcohol level at the legal limit. The purpose of this
      research was to provide a direct comparison of the driving performance of a cell
      phone driver and a drunk driver in a controlled laboratory setting. METHOD: We
      used a high-fidelity driving simulator to compare the performance of cell phone
      drivers with drivers who were intoxicated from ethanol (i.e., blood alcohol
      concentration at 0.08% weight/volume). RESULTS: When drivers were conversing on
      either a handheld or hands-free cell phone, their braking reactions were delayed
      and they were involved in more traffic accidents than when they were not
      conversing on a cell phone. By contrast, when drivers were intoxicated from
      ethanol they exhibited a more aggressive driving style, following closer to the
      vehicle immediately in front of them and applying more force while braking.
      CONCLUSION: When driving conditions and time on task were controlled for, the
      impairments associated with using a cell phone while driving can be as profound
      as those associated with driving while drunk. APPLICATION: This research may help
      to provide guidance for regulation addressing driver distraction caused by cell
      phone conversations.

PMID- 16884057
TI  - Does crew resource management training work? An update, an extension, and some
      critical needs.
AB  - OBJECTIVE: This review provides the state of crew resource management (CRM)
      training evaluations since the E. Salas, C. S. Burke, C. A. Bowers, and K. A.
      Wilson (2001) review and extends it to areas beyond aviation cockpits. Some
      critical evaluation needs in CRM training are also covered. BACKGROUND: Because
      of the purported success of CRM training in aviation, other high-consequence
      domains have begun to implement CRM training for their workforces. However, the
      true impact of CRM training in aviation and these other domains has yet to be
      determined. METHOD: Using D. L. Kirkpatrick's (1976) framework for evaluating
      training (i.e., reactions, learning, behavior, and organizational impact), we
      reviewed 28 published accounts of CRM training to determine its effectiveness
      within aviation, medicine, offshore oil production and maintenance,
      shipping/maritime, and nuclear power domains. RESULTS: Findings indicate that CRM
      training generally produced positive reactions from trainees; however, the impact
      of training on learning and behavioral changes suggest mixed results across and
      within domains. Furthermore, and as was found by Salas, Burke, et al. in 2001, we
      cannot ascertain whether CRM has had an impact on the organization's bottom line
      (i.e., safety). CONCLUSION: Based on the results, there are several critical
      needs that the CRM training community must address before CRM training can have
      the desired impact on safety: a mandate, access to data, and resources.
      APPLICATION: As CRM training expands to organizations beyond aviation, it is
      critical that its impact be understood such that it can be improved and achieve
      the intended results.

PMID- 16884058
TI  - [Prevention of second hand smoke: a public health example of collaboration
      between the medical community and government].

PMID- 16884059
TI  - [Prevention of air pollution by indoor tobacco smoke in France].
AB  - A majority of smokers and non-smokers mind tobacco smoke. Passive smoking causes
      death by sudden infant death, lung cancer and coronary heart disease. 3000 to
      6000 persons are killed every year in France. The lack of implementation of the
      Evin's law published in 1991 explains why non-smokers are not given the
      protection they can expect. The trend of scientific knowledge and of French and
      international public opinions support a growing demand for a complete protection
      of non-smokers with a total ban of smoking in all public or working places.

PMID- 16884060
TI  - [Smoking cessation intervention: 2006 update].
AB  - Recent Swiss reports confirmed that several chemical products added to cigarettes
      may increase the level of dependence and therefore the consumption of cigarettes.
      Observational studies demonstrated the association between smoking and type II
      diabetes, that smoking one to four cigarettes daily increases significantly the
      risk of disease and that the relative risk of breast cancer among non smoking
      women exposed to passive smoking is increased by 30%. The safety of nicotine
      replacement therapy for patients with cardiovascular disorders has been
      confirmed. Among new pharmacological approaches, varenicline, rimonabant,
      topiramate and nicotine vaccine all appear promising.

PMID- 16884061
TI  - [Women and tobacco: epidemiological and clinical specificities].
AB  - Cigarette smoking amongst women is a major issue in daily clinical practice and
      in public health. Tobacco is the cause of gender specific diseases. From a
      psychosocial point of view, female smokers tend to be emotionally vulnerable and
      relationship sensitive. The risk of weight gain and depression must be
      anticipated and assessed throughout the smoking cessation process. Professionals
      involved in smoking cessation must be aware of these somatic and psychosocial
      specificities in order to be able to offer efficient smoking cessation
      treatments. Public health strategies must also be developed worldwide to control
      the expected dramatic impact of the female tobacco epidemic.

PMID- 16884062
TI  - [The health consequences of smoking for women at different stages of their life].
AB  - Women who smoke underestimate the risks of smoking on their health, especially
      the impact of the anti-estrogenic and toxic effects of tobacco at the different
      stages of their life. The risk of female infertility related to tobacco is now
      well-proven, as is the risk of arterial and venous thrombotic event when tobacco
      is associated with oral contraception. Many foetal and maternal pathologies are
      linked to maternal smoking. Regarding post-menopausal women, smoking is
      associated with an increased osteoporotic and cardio-vascular risk. Doctors are
      at the first line to advise women and propose them help and assistance in their
      quit smoking process in a way adapted to their situation.

PMID- 16884063
TI  - [Reduction of cigarette consumption: an intermediate stage before a total stop?].
AB  - Reduction of cigarette consumption is a natural tendency of many undecided
      smokers and can be an intermediate stage before a total stop. It does not offer
      proven benefits regarding smoking-associated morbidity or mortality but seems to
      increase the motivation of smokers without intention to quit and the long-term
      chance of cessation. Smoking reduction can be offered to some smokers with
      smoking-related diseases as a transition before complete cessation. It can be
      obtained more easily with the use of nicotine replacement therapy.

PMID- 16884065
TI  - [Health promotion and prevention at school].

PMID- 16884064
TI  - [Smoking risk perception: facts and questions].
AB  - Based on general concepts relating to risk perception, the authors summarize in
      this article today's knowledge of smoking risk perception. A pluridisciplinary
      approach (general internal medicine, public health and anthropology) allows an
      improved understanding of its complexity, its utility in every day clinical
      practice and of the questions still pending around its use and evaluation in
      research projects.

PMID- 16884066
TI  - [Homosexuality and blood donation].

PMID- 16884067
TI  - [Human embryonic stem cells and the European Union].

PMID- 16884068
TI  - [The effects of contact lens wear on the physiology of the cornea].

PMID- 16884070
TI  - [The effect of preoperative topical antibiotics in cataract surgery].
AB  - PURPOSE: We studied whether topical antibiotics prevent endophthalmitis after
      cataract surgery. METHODS: Cefmenoxime hydrochloride (CMX) or artificial tears
      (AT) were randomly instilled 72 hours before surgery. Conjunctival swab samples
      were taken before the instillation of eye drops (1) and after the instillation of
      eye drops (2). Aqueous humor (3) was cultured intraoperatively. RESULTS: Positive
      cultures were found in the CMX group of eyes in 76.3% of (1) samples, 58.1% of
      (2) samples, and 6.0% of (3) samples. In the AT group of eyes, positive cultures
      were found in 78.6% of (1) samples, 63.8% of (2) samples, and 2.9% of (3)
      samples. CMX was not effective. In the CMX group of eyes, Staphylococcus
      epidermidis was found in 59 eyes of group (1), 5 eyes of group (2), and 0 eyes of
      group (3). In the AT group of eyes, S. epidermidis was found in 70 eyes of group
      (1), 26 eyes of group (2), and 1 eye of group (3). In the cases where S.
      epidermidis was decreased by CMX topical use Propionibacterium acnes was
      increased. CONCLUSIONS: There is a possibility that preoperative topical use of
      CMX can reduce S. epidermidis. On the other hand, it might increase P. acnes.
      Considering these results and the fact that there was no difference in
      effectiveness in the aqueous humor cultures, preoperative CMX topical use may not
      prevent postoperative endophthalmitis except for endophthalmitis due to S.
      epidermidis.

PMID- 16884069
TI  - [Relationship between compliance and background factors of glaucoma patients].
AB  - PURPOSE: To obtain useful information for the improvement of patient compliance
      in the medical treatment of glaucoma. SUBJECTS AND METHODS: An unsigned attitude
      survey on glaucoma and eye drops was conducted with 431 glaucoma patients.
      Correlation between compliance and individual(objective and subjective) factors
      was investigated. Objective factors were age, sex, number of eye drop products,
      duration of disease, and degree of visual field defects. Subjective factors were
      "stinging sensation with application of eye drops" and "worry about blindness".
      RESULTS: Thirty-eight percent of the glaucoma patients were compliant, instilling
      eye drops at the right time and with good technique. For the factor "duration of
      disease", patients who had glaucoma for 6-10 years had the best compliance.
      Compliance became poorer with an increasing number of eye drop products. In the
      subjective factors, less pain and worry led patients to better compliance.
      CONCLUSION: To improve compliance with medical treatment, we should categorize
      patients based on objective factors, eliminating their pain and worry, and
      instructing them not only in the frequency of instillation but also in the
      technique of administration.

PMID- 16884071
TI  - [The effect of disposable contact lenses on the corneal endothelium].
AB  - PURPOSE: The effect on the corneal endothelium of wearing long-term disposable
      contact lenses has not been described. We analyzed longitudinal data on long-term
      endothelial morphological changes in each eye of new wearers. SUBJECTS AND
      METHODS: We performed specular microscopy on the corneal endothelium of 78
      disposable contact lens users (145 eyes) who had not previously worn contact
      lenses at baseline and after 5 +/- 0.5 years. We analyzed the video images using
      computer-aided design (CAD) software. RESULTS: Although the mean cell area
      increased by only 3%, the coefficient of variation of cell area increased by 28%
      during 5 years of use. The range of the ratio of the coefficient of variation of
      cell area at 5 years to the baseline coefficient in young wearers was wider than
      that in adult wearers. The 9 eyes with a z-score for mean cell area exceeding
      1.64 to cut off 5% of the distribution from the right-hand tail at 5 years were
      derived from eyes that were above the average mean cell area for 145 eyes at
      baseline. With one exception, the 11 eyes with a z-score for the coefficient of
      variation of cell area over 1.64 at 5 years were eyes that had a medium mean cell
      area at baseline. In more than 70% of the 145 eyes, the data on cell area at 5
      years differed from baseline. CONCLUSIONS: The effect of wearing contact lenses
      on the corneal endothelium varies. Further studies of larger numbers of users are
      required.

PMID- 16884072
TI  - [Three cases of abducens nerve palsy accompanied by Horner syndrome].
AB  - PURPOSE: To report three cases of nasopharyngeal carcinoma, exhibiting abducens
      nerve palsy and Horner syndrome during the medical treatment of the tumor, whose
      invasive cavernous sinus lesions could be detected. SUBJECTS: The patients were
      two men and one woman who were referred to our department with complaints of
      diplopia during the clinical course of nasopharyngeal carcinoma. RESULTS: Right
      abducens nerve palsy, Horner syndrome, and impairment of the 1st division of the
      trigeminal nerve were recognized in all patients. Magnetic resonance imaging
      (MRI) revealed invasive lesions in the right cavernous sinus in all three
      patients, with iso-intensity on T1-weighted images, which were enhanced by
      gadolinium. CONCLUSIONS: The abducens and sympathetic nerves run closely together
      in the cavernous sinus. Nasopharyngeal carcinoma is apt to invade the cavernous
      sinus and often impairs the abducens nerve. Therefore the presence of Horner
      syndrome and trigeminal palsy in combination with abducens nerve palsy should be
      cautiously investigated to confirm the existence of the cavernous sinus lesions.

PMID- 16884073
TI  - [Two cases of retinal hemangioma treated by transpupillary thermotherapy].
AB  - PURPOSE: To evaluate transpupillary thermotherapy(TTT), the treatment was
      reviewed in two cases of retinal hemangioma which resisted photocoagulation. CASE
      1: A 25-year-old man was referred to us for visual impairment in his right eye
      caused by retinal hemangioma. Although photocoagulation had been performed once
      in a previous hospital, the treatment was unsuccessful. His visual acuity was 0.1
      OD. Ophthalmoscopic examination revealed a hemangioma located in the
      superotemporal peripheral retina with serous retinal detachment. We performed
      photocoagulation of the afferent artery and TTT of the hemangioma two times each.
      The hemangioma regressed and the serous retinal detachment resolved. The
      patient's visual acuity OD improved to 0.2. CASE 2: A 13-year-old girl was
      referred to us for visual impairment in her right eye caused by retinal
      hemangioma. Photocoagulation had been performed five times in a previous
      hospital, but the treatment was unsuccessful. Her visual acuity was 0.05 OD.
      Opthalmoscopic examination revealed a hemangioma located in the inferonasal
      peripheral retina with serous retinal detachment. We performed photocoagulation
      of the afferent artery two times and TTT of the hemangioma four times. The
      hemangioma regressed and the serous retinal detachment resolved. CONCLUSION: TTT
      is performed with a larger spot size, a longer wavelength, and a longer duration
      than photocoagulation. TTT could be an effective treatment for retinal
      hemangioma.

PMID- 16884074
TI  - Endodontic standard of care.

PMID- 16884075
TI  - The male dental assistant.

PMID- 16884076
TI  - Reflection in the glass.

PMID- 16884077
TI  - Oral candidiasis infections with limited clinical findings.

PMID- 16884078
TI  - Evaluation and treatment by general dentists of oral soft-tissue lesions.

PMID- 16884079
TI  - Effective laboratory communication...it's a two-way street.
AB  - Working as part of your team, your dental laboratory can increase your
      predictable success and decrease the stress of daily practice. This partnership
      should begin during the treatment planning phase and continue through to the
      insertion appointment. Many dentists are beginning to view their laboratory
      technician as a bonafide member of their patient care team. Thorough
      communication on both sides is crucial to reaching this predictable success. A
      trusting relationship will enable the dentist and the laboratory technician to
      communicate effectively. The laboratory must take the responsibility to
      communicate its concerns to the dentist, just as the dentist must take the
      responsibility to communicate effectively with the laboratory his or her needs
      and desires for each case. When effective communication techniques are followed,
      everyone is a winner. The dentist is more productive per hour and has reduced
      stress. The dental laboratory does not have to bear the burden of remakes, and
      spends less time on the phone or sending e-mail for routine cases. And most
      importantly, the patient receives an exceptional restoration that meets his or
      her expectations. In the end, the true measure of a great relationship between
      the dentist and the laboratory is happy patients who refer friends and family to
      your practice for years to come.

PMID- 16884080
TI  - Live longer, live better: lifestyle diseases and their prevention, part 2.

PMID- 16884081
TI  - Strategies for management of the apical third.

PMID- 16884082
TI  - Rules of engagement: mastering the endodontic game, part 2.
AB  - The rules of engagement are an overview of the essential elements needed to
      reconstruct endodontically volved teeth back to successful, healthy members of
      the dental arch that function and are biologically healthy, structurally strong,
      aesthetic, and valuable. Endodontics just keeps getting better and better, and
      the future of endodontic success is bright. Now more than ever patients value and
      appreciate dental aesthetics. Everyone wants to look good, smell good, and appear
      successful. Teeth will always play a major role in these human desires. The
      endodontic tooth can either be the "weakest link" or it can be as strong a link
      as any other healthy tooth. The choice is ours...if we play by the rules.

PMID- 16884083
TI  - Enhancing gingival harmony and smile line symmetry with conservative contouring
      and direct composite placement.

PMID- 16884084
TI  - A conservative and painless approach to anterior and posterior aesthetic
      restorative dentistry.

PMID- 16884085
TI  - Restoring aesthetics and function with a metal-free crown: case report.

PMID- 16884086
TI  - Survey reveals dentists' top worries.

PMID- 16884087
TI  - Information is king!

PMID- 16884088
TI  - [Training tutorial in laparoscopy].

PMID- 16884089
TI  - [Laparoscopy in urologic oncology].

PMID- 16884090
TI  - [Unresolved matter].

PMID- 16884091
TI  - [The Fosburi style, imagination, laparoscopy ... and Actas Urologicas Espanolas].

PMID- 16884092
TI  - [Animal models in urological laparoscopic training].
AB  - We present the experience of the Minimally Invasive Surgery Centre (MISC) in the
      development of a modular training model in laparoscopic surgery. The experience
      analysis includes the description of the training objectives, the learning
      process of simple and advance laparoscopic urologic techniques, as well as some
      current and future considerations before applying the laparoscopic techniques.
      This learning program pretends to optimize the knowledge of the surgeon and the
      clinical practice of these surgical techniques. The phases of the learning
      process have been classified in four levels, which include different modules and
      models and whose application will depend on the experience and surgical skills.
      This pyramidal training system permits the student to advance step by step
      through each level depending on her surgical skills. We have presented our
      experience in twelve courses about laparoscopic urology and four courses of
      laparoscopic radical prostatectomy, in which more than 300 urologists have
      assisted. Furthermore, some Spanish Urology Units have been developing special
      experimental training programs on laparoscopic radical prostatectomy, partial
      nephrectomy or laparoscopic dismembered pyeloplasty with Anderson-Hynes
      technique. It has been previously described that laparoscopic modular learning
      constitutes a very useful concept to avoid problems related to an incomplete and
      incorrect learning process. Also it seems clear that the laparoscopic training
      reduces the learning curve in laparoscopic urologic techniques.

PMID- 16884093
TI  - [Laparoscopic surgery training in pelvitrainer and virtual simulators].
AB  - Over the last few decades, there has been a rise in the number of minimally
      invasive techniques, such as arthroscopy, vascular radiology and our speciality,
      laparoscopy. Laparoscopy has resulted in a reduction in the damage caused during
      intervention, with the subsequent reduction in hospital stay, postoperative pain
      and infections. However, one disadvantage of these techniques is that they
      require a large investment in instruments and a long and costly training period.
      In the following chapter, we describe the laparoscopic training process of the
      medical residents from our Urology Service in the pelvitrainer and virtual
      simulator.

PMID- 16884094
TI  - [Traditional training devices for laparoscopy].
AB  - Laparoscopy is a new approach to urological surgery with a number of advantages.
      The learning of this technique is very important. In order to establish this
      technique as routine practice a considerable amount of training is needed. The
      learning curve is still very long and training methods are scarce. At the present
      time there are simple, low-cost simulators available that may be used in any
      place, thus facilitating training. We have reviewed recent literature on these
      models, which can be of great help in initial laparoscopic training.

PMID- 16884095
TI  - [Purpose of the practical training courses].
AB  - Laparoscopy surgery started in the 90's decade and it is rapidly developing in
      the first years of this century; it is therefore a very recent surgical
      alternative. This has made that each teams formation has gone along very
      different ways, today that we have already expert services it is essential to
      systematize the training and to shorten the learning curve. For that purpose we
      have the practical training courses that combine surgery in patients with surgery
      in experimental operating theatres, which are absolutely indispensable.

PMID- 16884096
TI  - [Teaching laparoscopic urologic oncology. The Memorial Sloan-Kettering Cancer
      Center experience].
AB  - OBJECTIVE: We outline the structure of the clinical and training program of
      laparoscopic urologic oncology at Memorial Sloan-Kettering Cancer Center. We
      discuss the steps and key elements necessary in acquiring lapa roscopic
      proficiency. MATERIAL AND METHOD: The program lasts 2 years and trains fellows
      and faculty. For fellows, the program consists of a 6 months high volume
      laparoscopic oncology rotation, during which dry lab, animal lab, vide review and
      operating room experience are required. For faculty, the program consists of 1
      accredited continuin medical education course, 20 hours of dry lab, 1 session
      animal lab, observation of laparoscopic cases, first assistant in a minimum of 15
      laparoscopic cases, performing laparoscopic cases under mentoring. RESULTS: 8
      fellows have completed the training, 4 of whom have completed their fellowship
      and are in academic centers, performing advanced laparoscopy. The laparoscopic
      approach represents on average 80% of their urologic practice. Three attendings
      are performing laparoscopic surgery with mentoring. CONCLUSION: The goals of a
      surgical education program should be the standardization of the acquisition o
      surgical skills and assessment of the performance in a uniform setting to ensure
      the maintenance of the acquisition of skills and to develop programs to teach new
      skills.

PMID- 16884097
TI  - [Development of a laparoscopic radical prostatectomy program in an university
      center].
AB  - The aim of this article is to report our experience in setting up a laparoscopic
      radical prostatectomy programme. We believe that knowledge of the difficulties we
      faced at the start will be useful for those who wish to implement a programme
      like ours. We hope that by explaining the steps we took as well as our
      conclusions and recommendations this difficult task can be made easier.

PMID- 16884098
TI  - [Ethics and training in laparoscopic surgery].
AB  - Teaching operative skills are of paramount importance to urology training,
      specially in the period of time of the residency. Because of that, the
      introduction of laparoscopy in our surgical activity must be followed by a
      careful planning of progressive training as an answer to this new need that would
      be well designed trying not to damage in whatever possible way to the patients
      operated with this new modality of surgical intervention. In this sense, each
      case and each indication of laparoscopy must be clarified individually, taking
      into account the basic principles of medical ethics (beneficency, no maleficency,
      justice and autonomy). So, it will be neccesary to decide about possible risks
      due to the experience of the surgeon or due to the modality of surgery. In this
      article, different options of training plannings in laparoscopy are mentioned
      taking as a reference the experience in laparoscopic prostatectomy, reasons of
      "prepared reconversion" are exposed and, finally, the authors explain the
      discussion about the subject and the extent of information offered to the
      patients looking for the best possibilities of decision making by the patients.

PMID- 16884099
TI  - [Radical laparoscopic nephrectomy].
AB  - In this article, we review the different surgical approaches to carry out radical
      laparoscopic nephrectomy: transperitoneal approach, retroperitoneal approach and
      hand-assisted approach. We describe the advantages and drawbacks of each
      alternative and summarize the most important references in the medical
      literature. In spite of this being a relatively new surgical approach, less than
      15 years old, it has become a standard treatment and, today, is considered as the
      elective surgical treatment for T1 and T2 renal tumours in many centres.

PMID- 16884100
TI  - [Transperitoneal laparoscopic partial nephrectomy in the renal tumor treatment].
AB  - Laparoscopic surgery is a surgical technique the urologist should add to his
      surgical armamentarium. Its performance tries to mimic the surgical phases of
      open surgery, and also its indications. Laparoscopic partial nephrectomy is a
      sophisticated technique that requires wide experience in the performance of
      endoscopic strategies. We are submitting our experience with 35 laparoscopic
      partial transperitoneal nephrectomies with a mean follow-up of 25 months. The
      mean surgical time was 200 minutes, the mean bleeding 190 cc, and the mean
      hospitalisation five days. Two postoperative bleedings were identified, there
      were no conversions, and positive margins were notified in two cases, where upon
      a conservative attitude was adopted.

PMID- 16884101
TI  - [Laparoscopic partial nephrectomy: technique and outcomes].
AB  - The indication of laparoscopic partial nephrectomy (LPN) has evolved
      considerably, and the technique is approaching established status at our
      institution. Over the past 5 years, the senior author has performed more than 450
      laparoscopic partial nephrectomies at the Cleveland Clinic. Herein we present our
      current technique, review contemporary data and oncological outcomes of LPN.

PMID- 16884102
TI  - [Radical laparoscopic nephroureterectomy].
AB  - As with the increasingly common presence of laparoscopic surgery in renal
      adenocarcinoma, the same situation is also occurring with radical management of
      tumours of the upper urothelium. In this type of clinical condition, it is
      important to emphasize the different ways to mobilise the distal ureter (with
      transuretral resection or unroofing, pure laparoscopy, or open), and to take into
      account that this tumour has the highest risk of implantation at the ports of
      entry. Here, we conduct a literature review and up-date of the different
      approaches to the distal urethra.

PMID- 16884103
TI  - [Laparoscopic adrenalectomy].
AB  - Laparoscopic extirpation of the suprarenal gland is considered the 'gold
      standard' of surgery for benign conditions, but its indication in suprarenal
      cancer is still controversial. In this article, we review the pros and cons of
      the laparoscopic approach in the different disorders that affect the adrenal
      gland, pheochromocytoma, cancer, partial and bilateral adrenalectomy, etc.

PMID- 16884104
TI  - [Current status of radical laparoscopic prostatectomy].
AB  - Laparoscopic surgery can be said to have come of age when it was first indicated
      for cancer conditions. Advances in this field are largely due to the French
      school, which has made it a standard practise in prostate cancer. It complies
      with the principles required for cancer as well as conventional surgery, but it
      remains to be verified whether its long-term results, both from tumoral and
      functional perspectives, are not only similar to those of classical surgery, but
      even better. In fact, increasing numbers of clinical groups are incorporating
      this technique in their daily work.

PMID- 16884105
TI  - [Analysis of a laparoscopic radical prostatectomy program with 544 cases].
AB  - INTRODUCTION: This article reviews the latest publications that refer to
      Laparoscopic Radical Prostatectomy (LRP) up to 2005, and describes our series of
      patients for this type of surgery. MATERIALS AND METHODS: After a search of the
      Internet and consulting journals of renowned prestige, we selected articles that
      refer to this technique and we summarise the latest developments in LRP. We also
      present our series of patients. RESULTS: In view of the good oncologic and
      functional results obtained with LRP, and the possibility of performing
      hernioplasty as in open surgery, this technique provides a high quality service
      for patients. CONCLUSIONS: Due to the advances in the safety and quality of this
      technique, such as the use of robots, 3 CCD cameras, and the surgeon's
      experience, LRP should be offered to our patients, if it is within our means.

PMID- 16884106
TI  - [Radical laparoscopic cystectomy].
AB  - Radical laparoscopic cystectomy is being adopted by most groups with proven
      experience in laparoscopic surgery, especially by those who have already
      completed the learning curves in radical laparoscopic prostatectomy. It is still
      considered a highly complex technique, which has not yet been mastered in many
      Urology Units. In this article, we review the surgical technique and available
      literature on this approach, with special emphasis on its indications, advantages
      and most frequent morbidity.

PMID- 16884107
TI  - [Complications of laparoscopic urological procedures].
AB  - Laparoscopic urology has evolved considerably during last decade as well as
      number and spectrum of surgical related complications. Experiences reported by
      laparoscopic trained groups allow preventing, promptly recognizing, and safe and
      efficient management of the laparoscopic related complications. We present our
      complications in all patients undergoing urological laparoscopic procedures from
      November 1992 to June 2005. A literature search was conduced to evaluate
      complications of every laparoscopic procedure.

PMID- 16884112
TI  - [Migrant children].

PMID- 16884113
TI  - [Discovering Gypsies].

PMID- 16884114
TI  - [Care of migrants].

PMID- 16884115
TI  - [How to help migrant children surmount their difficulties at school?].

PMID- 16884116
TI  - [Nursing care for Gypsies in the Saintonge country. Interview by Genevieve
      Binel].

PMID- 16884117
TI  - [With Gypsy children].

PMID- 16884118
TI  - [National Federation of Health Associations for Gypsies and Migrants].

PMID- 16884119
TI  - [The child and life change events].

PMID- 16884120
TI  - [Living after an acute lymphoblastic leukemia].

PMID- 16884121
TI  - Introduction to the rapid response systems series.

PMID- 16884122
TI  - Using an MET service to manage an acute thromboembolic stroke.
AB  - The hospital's medical emergency team expedited involvement of all required
      services when it was called in twice for episodes of bleeding.

PMID- 16884123
TI  - Improving the safety of intravenous admixtures: lessons learned from a Pentostam
      overdose.
AB  - CASE STUDY: Weaknesses in the multistep process of admixture preparation and
      administration resulted in a patient with cutaneous leishmaniasis (CL) receiving
      a 10-fold intravenous (IV) overdose of Pentostam (sodium stibogluconalte), a
      rarely used drug. LESSONS LEARNED: A review of this adverse event resulted in
      five recommendations: (1) Provide staffing continuity among pharmacists and
      pharmacy technicians preparing and nurses administering the admixture; (2) Take
      time to ensure thorough and deliberative consideration ofquestions or concerns
      about admixture preparation; (3) Use due diligence in performing double checks of
      admixture calculations; (4) Know the drug and seek clarification when
      appropriate; and (5) Examine label information carefully. PROGRESS UPDATE: Two
      changes were made to improve patientsafety. First, a form was developed to
      accompany the preparation of complex IV drugs, including chemoltherapy solutions
      and nonformulary IV admixtures; the form is consistently used. Second, the
      pharmacy service developed information sheets for 12 high-risk drugs frequently
      used in IV admixtures. DISCUSSION: The medical center had processes in place to
      prevent medication errors, yet an error occurred nonetheless. Weaknesses were
      identified in staff communication, quality assurance checks, and product
      labeling. Also, nurses and pharmacists had less than adequate information about
      new or unusually dosed medications.

PMID- 16884124
TI  - Using HFMEA to assess potential for patient harm from tubing misconnections.
AB  - BACKGROUND: Reported cases of tubing misconnections and other tubing errors
      prompted Columbus Children's Hospital to study their potential for harm in its
      patient population. A Health Failure Mode and Effects Analysis (HFMEA) was
      conducted in October 2004 to determine the risks inherent in the use and labeling
      of various enteral, parenteral, and other tubing types in patient care and the
      potential for patient harm. METHODS: An assessment of the practice culture
      revealed considerable variability among nurses and respiratory therapists within
      and between units. Work on an HFMEA culminated in recommendations of risk
      reduction strategies. These included standardizing the process of labeling of
      tubing throughout the organization, developing an online pictorial catalog to
      list available tubing supplies with all aliases used by staff, and conducting an
      inventory of all supplies to identify products that need to be purchased or
      discontinued. Three groups are working on implementing each of the
      recommendations. RESULTS: Most of the results already realized occurred in
      labeling of tubing. The pediatric intensive care unit labels all tubing with
      infused medications 85% of the time; tubings inserted during surgery or in
      interventional radiology are labeled 53% and 93% of the time. Pocket-size cards
      with printed labels were tested in three units. DISCUSSION: This proactive risk
      assessment project has identified failure modes and possible causes and
      solutions; several recommendations have been implemented. No tubing
      misconnections have been reported.

PMID- 16884125
TI  - Getting doctors to report medical errors: project DISCLOSE.
AB  - BACKGROUND: Despite the number of patient safety incidents that occur in
      hospitals, physicians currently may not have the ideal incident reporting tools
      for easy disclosure. A study was undertaken to assess the effectiveness of a
      simplified paper incident reporting process for internal medicine physicians on
      uncovering patient safety incidents. DESIGN: Thirty-nine internal medicine
      attending physicians were instructed to incorporate the use of a simplified paper
      incident reporting tool (DISCLOSE) into daily patient rounds during a three-month
      period. All physicians were surveyed at the conclusion of the three months.
      RESULTS: Compared with physician reporting via the hospital's traditional
      incident reports from the same time period, a higher number (98 incidents versus
      37; a 2.6-fold increase) of incidents were uncovered using the DISCLOSE reporting
      tool in a larger number of error categories (58 versus 14, a 4.1-fold increase).
      When reviewed and classified with a five-point harm scale, 41% of events were
      judged to have reached patients but not caused harm, 33% to have resulted in
      temporary harm, and 9% of reports, though not considered events, were to indicate
      a "risky situation." Surveyed physicians were more satisfied with the process of
      submitting incident reports using the new DISCLOSE tool. DISCUSSION: A simplified
      incident reporting process at the point of care generated a larger number and
      breadth of physician disclosed error categories, and increased physician
      satisfaction with the process.

PMID- 16884126
TI  - Implementing Six Sigma in The Netherlands.
AB  - BACKGROUND: Six Sigma, a process-focused strategy and methodology for business
      improvement, can be used to improve care processes, eliminate waste, reduce
      costs, and enhance patient satisfaction. EXPERIENCE WITH SIX SIGMA IN THE
      NETHERLANDS: Six Sigma was introduced in 2001 at the 384-bed Red Cross Hospital
      (Beverwijk). During the Green Belt training, every participant was required to
      participate in at least one Six Sigma project. The hospital's total savings in
      2004 amounted to 1.4 million dollars, for an average savings of 67,000 dollars
      for each of the completed 21 projects. THREE EXAMPLES OF SUCCESSFUL PROJECTS: In
      one project, the team designed a new admission process for the operating rooms,
      resulting in an average starting time nine minutes earlier. This relatively minor
      improvement made it possible to operate on an additional 400 patients a year and
      to achieve a net savings of >273,000 dollars. A second project reduced the number
      of patients receiving intravenous (IV) antibiotics by switching to oral
      administration, yielding annual savings, based on medication costs alone, of
      >75,000 dollars. A third project reduced the length of stay in the delivery room
      from 11.9 to 3.4 hours, yielding an annual savings of 68,000 dollars. The
      "Ultimate Cure?": Six Sigma, which entails involvement of health care workers;
      use of improvement tools (from industry); creation of trained project teams to
      tackle complex, often cross-departmental processes; data analyses; and investment
      in quality improvement may prove the "ultimate cure" to the current cost,
      quality, and safety issues that challenge health care.

PMID- 16884127
TI  - Improving health care quality and safety for people with disabilities: an
      interview with Lisa Iezzoni. Interview by Steven Berman.
AB  - Dr. Iezzoni addresses issues in the quality and safety of health care for people
      with disabilities, who may be especially likely to experience problems in care.

PMID- 16884128
TI  - Operating room debriefings.
AB  - This tool helps assess factors that positively and negatively contributed to an
      adverse event, near miss, or inefficiency during an operation-or any procedure.

PMID- 16884129
TI  - Tubing misconnections--a persistent and potentially deadly occurrence.

PMID- 16884131
TI  - The birth of advanced trauma life support.

PMID- 16884132
TI  - The use of retrievable inferior vena cava filters in trauma: implications for the
      trauma team.
AB  - Prevention of venothromboembolic complications remains a challenge in trauma
      care. Guidelines for prophylaxis published by the Eastern Association for the
      Surgery of Trauma stratify patients by risk and recommend therapies based on
      scientific evidence. New innovations such as retrievable inferior vena cava
      filters are being used by trauma surgeons for patients at risk for pulmonary
      embolism but in whom anticoagulation is contraindicated. Some available devices
      offer a limited timeframe for retrieval beyond which the device becomes
      permanent. The increased utilization of this technology presents case management
      challenges to trauma teams. Patients who are unreliable or may be difficult to
      track posthospitalization (homeless, migrant workers, prison system, etc.) run
      the risk of not having their filters removed as initially intended. Nurses can
      play a critical role in helping to manage and direct the discharge plan and case
      management of trauma patients with retrievable inferior vena cava filters.

PMID- 16884133
TI  - Leadership editorial: The Self-Empowerment Pledge.
AB  - The Self-Empowerment Pledge includes 7 simple promises that can help caregivers
      be more effective in both their personal and professional lives. When shared with
      trauma patients and their families, these promises can help fortify them mentally
      and emotionally for the challenges of recovery.

PMID- 16884134
TI  - Mild traumatic brain injury in children: just another bump on the head?
AB  - Mild traumatic brain injury (MTBI) is frequently encountered in pediatrics and
      challenges healthcare practitioners to provide safe, consistent, cost-effective
      care. Clinical management of children who sustain MTBI poses dilemmas for
      healthcare practitioners. This article will provide an overview of pediatric MTBI
      including definition, issues impacting diagnosis and management, risk factors for
      intracranial injury, indications for diagnostic imaging, disposition, and return
      to sports/activity. Knowledge and understanding of MTBI in children aid
      healthcare practitioners to make informed competent recommendations for care.
      Clinicians must have a thorough understanding and working knowledge of pediatric
      MTBI to aid clinical decisions and optimize patient outcomes.

PMID- 16884135
TI  - Pediatric trauma nurse practitioners increase bedside nurses' satisfaction with
      pediatric trauma patient care.
AB  - PURPOSE: Our Level I Pediatric Trauma Center employs pediatric nurse
      practitioners (PNP) to manage inpatients. We hypothesized that the involvement of
      a PNP would lead to increased nursing staff satisfaction with patient care.
      METHODS: Children admitted to the trauma service were randomized to PNP or
      resident care groups. Nurses caring for these children were asked to fill out a
      satisfaction survey regarding the care that the child received. FINDINGS: Sixty
      five nurses participated. Nurses scored the PNP group significantly higher in
      human qualities, information given about the tests, management of the child's
      pain, and response time to pages/questions. CONCLUSIONS: Involvement of the PNP
      leads to higher nursing satisfaction scores compared with residents while
      providing equivalent care for injured children.

PMID- 16884136
TI  - Trauma case management: a role for the advanced practice nurse.
AB  - The care of a critically ill trauma patient is complex and requires the expertise
      and skill of many healthcare providers. Delays in injury identification and the
      development of a treatment plan without considering comorbid conditions impede
      the patient's resuscitation and recovery from the acute injury, delay the
      rehabilitative phase, and increase the costs. This article will discuss a
      strategy using an advanced practice nurse as a case manager to assist in prompt
      identification of the patients' pathologic and physiologic changes and
      psychosocial and rehabilitative needs and to orchestrate a comprehensive and
      consistent plan through the continuum of care.

PMID- 16884137
TI  - Are you ready to execute your facility's emergency management plans?
AB  - Within the context of emergency management, the difference between preparedness
      and readiness is discussed. A 5-step approach is presented to help identify the
      readiness of individuals to execute their facility's emergency management plans.
      Step 1 is a 10-question self-evaluation. Suggestions for identifying individual
      and plan deficiencies are also presented. A short discussion regarding emergency
      management exercises/drills and their importance is provided. In addition,
      information regarding Hospital Emergency Incident Command System III and the new
      Hospital Emergency Incident Command System IV compliance with the National
      Incident Management System is also presented. The argument can be made that no
      one is ever fully prepared or is 100% ready because readiness is an ongoing
      development process. Although that may be true, one can reasonably prepare for
      identified potential events. Readiness certainly falls within the scope of
      continuous quality improvement.

PMID- 16884138
TI  - Look beneath the skin: an unlikely source of median nerve injury.
AB  - A 4 1-year-old man presented with an occult median nerve injury. This report
      highlights the importance of adequate wound exploration and reinforces the
      significance of adequate history and examination in patients with signs of nerve
      injury.

PMID- 16884139
TI  - Cervical spine clearance in the blunt trauma patient: a review of current
      management strategies.
AB  - The risks of overlooking a cervical spine injury in a polytrauma patient still
      remain substantial even with the development of recent advanced radiologic
      imaging and practice management guidelines. Cervical spine clearance continues to
      pose a diagnostic dilemma to the trauma team providing care for these patients.
      There are several issues with legal, medical, and economic implications: which
      patient populations require cervical spine radiographs; which views should be
      obtained; is there efficacy in flexion/extension radiographs, CT scan, or MRI
      scans; in the obtunded patient can the absence of significant ligamentous injury
      be demonstrated; who should perform clearance methods and be ultimately
      responsible for valid clearance. The purpose of this article is to revisit
      current management strategies for clearance of the cervical spine and explore new
      findings if any, which have been accepted as standard of care by providers, faced
      with this challenging responsibility.

PMID- 16884140
TI  - A new moral consensus is needed for medical decision making.

PMID- 16884141
TI  - Realizing the research potential of the NHS.

PMID- 16884143
TI  - Manometry and 24-hour pH monitoring in diagnosis and management of GORD.

PMID- 16884142
TI  - Irritable bowel syndrome: anxiety in gastroenterology.

PMID- 16884144
TI  - Surveillance and screening of Barrett's oesophagus.

PMID- 16884145
TI  - Treatment of rare cancers: gastrointestinal stromal tumours.

PMID- 16884146
TI  - Conducting a mental state examination.

PMID- 16884147
TI  - Medical students' attitudes to modernising medical careers: will it affect
      training or career choice?

PMID- 16884148
TI  - Metatarsal fractures.

PMID- 16884149
TI  - Interpretation of paediatric trauma.

PMID- 16884150
TI  - So you want to be... a geriatrician.

PMID- 16884151
TI  - Cancer vaccines: a clinical perspective.

PMID- 16884152
TI  - Chronic obstructive pulmonary disease, inflammation and PDE4 inhibitors.

PMID- 16884153
TI  - What makes a good doctor in the 21st century? A qualitative study.

PMID- 16884154
TI  - Painful swollen legs in a diabetic patient.

PMID- 16884155
TI  - Arterial dissection and cerebral venous thrombosis in sickle cell trait.

PMID- 16884156
TI  - Subependymal nodular heterotopia.

PMID- 16884157
TI  - The patient who threatens to self-discharge.

PMID- 16884158
TI  - Paediatric endotracheal tubes: cuffed or uncuffed?

PMID- 16884159
TI  - [Violence against Mexican women].

PMID- 16884160
TI  - [Violence scale and severity index: a methodological proposal for measuring
      violence by the partner in Mexican women].
AB  - OBJECTIVE: To construct and validate a scale to assess violence by the male
      partner against women. An index of severity of the emotional and physical damage
      was also designed to assess the intensity of the violent actions against women.
      MATERIAL AND METHODS: The sample consisted of a total of 26 042 women who
      participated as respondents in the National Survey on Violence against Women
      (ENVIM per its abbreviation in Spanish) conducted in Mexico during 2003.
      Respondents were all users of health services provided by the Mexican government.
      The questionnaire was organized into 17 sections, one of which was a 27-item
      scale to assess partner violence. The purpose of this scale was to measure the
      type (physical, emotional, sexual and financial) and degree of violence based on
      severity. A severity index was constructed based on two procedures: 1) the
      validity, reliability, and factor analyses of the scale and 2) the assessment of
      severity by expert judges who assigned a value to each item of the scale.
      RESULTS: The validity and reliability results indicated this scale has adequate
      internal validity (Cronbach's Alpha = 0.99). The factor analysis with Varimax
      rotation yielded a four-factor solution. The factors were: 1) Psychological
      violence; 2) Physical violence; 3) Severe physical violence; and 4) Sexual
      violence. The combination of the four factors accounted for 62.2% of the variance
      in the scale. Using the ratings from the judges a table of values for each of the
      violent actions described was obtained. The scores assigned by the judges ranged
      from 0 to 354. Results revealed a prevalence of 21% partner violence in the last
      twelve months. The prevalence of psychological violence was 18.5%; of physical
      violence 10.1%; severe physical violence 6.7% and sexual violence 7.0%.
      CONCLUSION: The scale of violence described in this article is a very useful and
      reliable instrument to assess marital violence against women. It is suggested
      that this instrument be used in other settings to compare results with different
      samples.

PMID- 16884161
TI  - [Gender violence prevalence in female users of health services in Mexico].
AB  - OBJECTIVE: To identify the prevalence of violence against females among those who
      are health service beneficiaries in Mexico. MATERIAL AND METHODS: The National
      Survey on Violence against Women (ENVIM, per its Spanish abbreviation) was
      applied in 2003 to female users of public primary and secondary health care
      services. The sampling framework was based on a stratified, probabilistic sample
      in two stages. First the health care units were selected with probability
      proportional to the number of physicians' offices in the unit, from a list of
      possible care units. Second, women 15 years and older who sought care at the
      health care unit were selected for participation in the study through systematic
      sampling. Univariate analysis and then bivariate analysis were carried out on the
      data collected with a questionnaire. RESULTS: The sample included 26 042 women
      between 15 and 92 years of age, with a mean age of 35.8 years. Physical violence
      during childhood was reported by 42% of the women. Only 7.8% answered yes to a
      general question about whether they experienced domestic partner violence, but
      21.5% reported experiencing violence of any type during the last 12 months as
      measured by a scale including specific acts of psychological, economic, physical
      and sexual violence. The most frequently reported type of violence was
      psychological (19.6%). Of the women who had been pregnant, 14.1% reported having
      experienced violence during pregnancy, and 4.4% reported being hit in the
      abdomen. The prevalence of sexual violence was 17.3% and close to half reported
      being victims of this type of violence before age 15. Higher prevalence of
      violence was found among women with lower levels of formal education, living in a
      rented home, in areas with higher overcrowding indices, and users of Ministry of
      Health care services. CONCLUSIONS: Identifying and measuring violence is complex,
      given the diverse types of violence and how they are perceived and therefore
      reported by women themselves. This is an important public health problem, in view
      of the high frequency observed in this study and the immediate implications.
      These findings indicate the urgent need for interventions to prevent and treat
      violence.

PMID- 16884162
TI  - [Violence and pregnancy in female users of Ministry of Health care services in
      highly deprived states in Mexico].
AB  - OBJECTIVE: To characterize intimate partner abuse and identify the main factors
      associated with violence in pregnancy in four highly deprived States in Mexico.
      MATERIAL AND METHODS: The data were taken from the National Survey on Violence
      against Women 2003 (ENVIM per its abbreviation in Spanish). Based on it a cross
      sectional study was conducted on 1 949 women between 15 and 50 years of age, who
      were once pregnant and who utilized primary and secondary health care services
      from the Ministry of Health, Mexican Institute of Social Security, and the
      Institute for Social Security and Services for State Workers in Guerrero,
      Hidalgo, Oaxaca and Chiapas states, between November 2002 and March 2003.
      Logistic regression was used to assess the association between independent
      variables and violence during pregnancy. RESULTS: 250 women (13%) suffered a type
      of violence (physical, psychological, sexual or economical) during any of their
      pregnancies. Of these women 76 (30.40%) were battered on their abdomen. In most
      of these cases (91.39%) the husband was the aggressor. The variables
      significantly associated with violence in pregnancy were: woman's illiteracy (OR
      2.2; CI 95:% .1,4.4); history of violence in childhood (OR 3.2; CI 95% 1.9, 5.4)
      as well as sexual abuse in her childhood (OR 2.4, CI 95% 1.3, 4.4) and her
      partner's daily alcohol consumption (OR 6.5; CI 95% 3.3, 12.9). CONCLUSIONS: The
      results show that violence during pregnancy is a regular event in the
      impoverished context and that its expression is more severe. These results point
      to the importance of continued study of the problem of violence against pregnant
      women in Mexico and the importance of identifying battered women in prenatal
      care.

PMID- 16884163
TI  - [Gender violence and other factors associated with emotional distress in female
      users of public health services in Mexico].
AB  - OBJECTIVE: To identify and describe the factors associated with emotional
      distress in a national sample of women users of public health services in Mexico,
      such a Secretaria de Salud (SSA), Instituto Mexicano del Seguro Social (IMSS),
      Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado
      (ISSSTE). MATERIAL AND METHODS: This research study was conducted using the
      database of the National Survey of Violence against Women that consisted of the
      responses of a total of 26 042 female users of health care services provided by
      the Mexican government health agencies. The Personal Health Scale (ESP per its
      initials in Spanish) was used to assess emotional distress. To measure violence a
      19-item scale which explores different types of violence as well as severity was
      used. The relationship between emotional distress and gender violence was
      determined through a binary logistic regression model, as were economic status
      and demographic variables. RESULTS: One of the most important findings of this
      study is the high prevalence of emotional distress (15.3%) among women seeking
      health care services from the public sector and the relationship of such
      emotional distress with the experience of marital physical, psychological, and
      sexual violence. Factors associated with emotional distress among female users of
      health care services were age (26 and older); activity (laborer); working hours
      (71 hours a week or more); alcohol intake (greater intake); abuse during
      childhood (frequency and types of abuse); severity of marital violence (severe
      violence); socioeconomic status (very low SES); and type of dwelling (urban).
      CONCLUSIONS: The principal predictor of emotional distress was intimate partner
      abuse, especially in severe expression. The next predictor was violence in
      childhood. Taking into consideration these predictors it is recommended to use
      screening instruments to identify emotional distress and gender violence in
      health setting. It is important to design and implement attention and reference
      programs in public health services for women suffering from emotional distress
      and gender violence.

PMID- 16884164
TI  - [Between denial and helplessness: health care providers facing domestic violence
      in Mexico].
AB  - OBJECTIVE: To increase the knowledge of health care providers' understanding of
      and practices on domestic violence, in order to improve care. MATERIALS AND
      METHODS: This study was conducted between May and November 2003, In Quintana Roo,
      Coahuila, and Mexico City, three Mexican states with a high prevalence of
      domestic violence. Sixty in-depth interviews with health care providers in public
      health institutions and key informants of health service provision were
      completed. RESULTS: Health care providers were categorized based on the extent to
      which they reproduced four"discourses about violence". These discourses influence
      their daily practice and are related to the informants' gender values and social
      positions. Most informants expressed their willingness to address the issue of
      domestic violence. CONCLUSIONS. Attention to and care for domestic violence is
      insufficient in health services; this may be due more closely related to a
      predominant discourse tolerating domestic violence among decision-makers, than to
      the attitudes of health care providers; the latter demonstrated greater awareness
      of women's rights.

PMID- 16884165
TI  - [Physical and sexual abuse during childhood and revictimization during adulthood
      in Mexican women].
AB  - OBJECTIVE: To quantify the association between physical and sexual abuse during
      childhood and violence during adulthood in a representative sample of female
      health care users in Mexico. MATERIAL AND METHODS: A questionnaire was
      administered to 26 042 women over 14 years of age who sought medical consultation
      from public health care services between October 2002 and March 2003, in all 32
      states in Mexico. Two models were constructed: a) Multiple polytomic logistic
      regression models to explore the association between violent victimization by the
      partner during adulthood and violence during childhood. b) Multiple logistic
      regression models to explore the association between experiencing rape during
      adulthood and violence during childhood. RESULTS: Among women studied, an
      association was found between experiencing physical violence during childhood and
      suffering physical and sexual violence from the male partner or experiencing
      rape, during adulthood. When physical violence during childhood occurred "almost
      always", it was more likely that the woman undergo physical and sexual violence
      (OR = 3.1; 95% CI 2.6-3.7) and rape (OR = 2.9; 95% CI 2.4-3.6), during her adult
      life. In addition, when violence during childhood was more frequent, the
      likelihood of experiencing violence during adulthood was greater. A positive
      association was found between physical and sexual abuse before 15 years of age
      (OR = 2.8; 95% CI 2.2-3.5). Experiencing rape during adulthood was also
      associated with sexual abuse before 15 years of age (OR = 11.8; 95% CI 10.2
      13.7). CONCLUSIONS: In this sample of Mexican women, both physical and sexual
      violence during childhood has negative results during adulthood, including a
      greater likelihood of revictimization by the male partner and rape. Physical and
      sexual abuse during childhood must be prevented or at least detected and treated.

PMID- 16884166
TI  - [Violence in Mexican women using public health services].
AB  - OBJECTIVE: To compare the prevalence of violence and determine its risk factors
      among women who use Mexican Social Services (IMSS) clinics and do not have access
      to social security services. MATERIAL AND METHODS: Sociodemographic data linked
      to domestic violence reported by women attending the Mexican Institute of Social
      Security (IMSS) health services was analyzed. Bivariate and multivariate analysis
      was performed using STATAV.7. RESULTS: Psychological violence in IMSS women was
      18% followed by physical violence (9.1%), sexual (6.7%) and economic (5%).
      Prevalence of violence in women with no social security care was psychological
      (21.4%), physical (10.5%), sexual (7.5%) and economical (5%). Women between 25
      and 44 years of age with basic schooling and married and with family background
      of violence were the most affected. The daily consumption of alcohol by their
      partners was an important predictor of domestic violence. CONCLUSION: Violence in
      women with no social security is higher. Partner's alcohol intake pattern is an
      important risk factor. Detection of domestic violence in the clinical setting is
      necessary to recognize its real magnitude as a social problem.

PMID- 16884167
TI  - [Dating violence and associations with depression and risk behaviors: female
      students in Morelos, Mexico].
AB  - OBJECTIVE: Determine the prevalence of dating violence and its association with
      depression and various risk behaviors in a sample of female students from the
      state of Morelos. MATERIAL AND METHODS: This is a baseline cohort study of a
      sample of 13 293 students from 12 to 24 years of age who attended public schools
      in the state of Morelos during the 1998-1999 school year. The participants were
      selected from a random sample of 260 junior high schools, 92 high schools and one
      university. For the purpose of this analysis, a total of 4 587 female students
      who had a previous dating relationship were selected. To control for possible
      confounding variables, multiple logistic regression analysis was used. RESULTS:
      The total prevalence of dating violence in females who attended public schools in
      Morelos was 28%. The following variables were associated with dating violence:
      depression (OR = 1.92; 95% CI 1.61-2.28); tobacco smoking (OR = 1.31; 95% CI 1.06
      1.60); alcohol abuse (OR = 1.30, 95% CI 1.12-1.51); poor academic performance
      (low grades) (OR = 1.25; 95% CI 1.03-1.52); a history of sexual relations (OR =
      1.52; 95% CI 1.26-1.82). CONCLUSIONS: The results of this study clearly indicate
      that women experience partner violence beginning with dating during adolescence.
      Health and education professionals need to establish intervention strategies to
      prevent or treat dating violence among female students. Such strategies should
      take into account the association between depression and violence, as well as
      other related risk behaviors.

PMID- 16884169
TI  - [Women's perceptions on intimate partner violence in Mexico].
AB  - OBJECTIVE: To identify personal, cultural, and institutional factors that hinder
      the solution to domestic violence. MATERIAL AND METHODS: In Quintana Roo,
      Coahuila, and Mexico City, 26 in-depth interviews with women currently suffering
      from intimate partner violence and others who had already found a solution were
      carried out, between May and November 2003. RESULTS: Among women's explanations
      to violence, it was possible to distinguish between causes (non intentional
      violence) and motives (intentional violence). Associated with these explanations,
      issues related to tolerance emerge, as well as attribution of responsibility.
      Moreover, the social ties of the women contribute to the acting out of gender
      roles and the justification or tolerance of conjugal abuse. CONCLUSIONS: The
      dominant values and norms of gender in society, shared by abused women and the
      community, are responsible for the perpetuation of intimate partner violence.

PMID- 16884168
TI  - [The contribution of violence to maternal mortality in Morelos, Mexico].
AB  - OBJECTIVE: To document the under-registration of violent deaths related to
      pregnancy and the importance of considering these violent deaths within the
      definition of maternal mortality. MATERIAL AND METHODS: The study was carried out
      in the state of Morelos, based on the review of all death certificates (394) of
      reproductive aged women (12-49 years) who died during 2001. Based on a list of
      diagnostic criteria we eliminated 167 certificates that were neither violent
      deaths nor maternal deaths. The remaining 227 certificates were further evaluated
      through verbal autopsy and/or review of medical charts. RESULTS: Fifty-one
      violent deaths were found. Eighteen maternal deaths were officially reported in
      2001, however, our study identified 23 direct maternal deaths and four violent
      deaths during pregnancy and the post-partum period. We found that this
      reproductive event was the direct trigger for the homicide or suicide of these
      four women, and only one of these cases was documented officially. CONCLUSIONS:
      Violent deaths related to pregnancy should be included in official maternal
      mortality statistics as indirect causes of maternal deaths. This would allow for
      a greater and more accurate understanding of violent maternal deaths and guide
      appropriate prevention and care policies, programs and services. Verbal autopsy
      is a useful technique for identifying cases of violent maternal deaths.

PMID- 16884170
TI  - [Male violence against heterosexual partners: facts and challenges. Review of
      Mexican literature].
AB  - Violence against women by partners (VAWP) has been systematically studied in
      Mexico in the past 15 years. The aim of this paper is to reflect on the
      contributions on this topic in Mexico. The discussion focuses on the magnitude of
      this phenomenon, stressing its theoretical, methodological, and technical
      implications; the relationship between violence and a variety of factors; and the
      outcomes of VAWP on women themselves. The manuscript features the main
      contributions from quantitative and qualitative studies.

PMID- 16884171
TI  - [Methodological design for the National Survey Violence Against Women in Mexico].
AB  - OBJECTIVE: To describe the methodology, the research designs used, the estimation
      and sample selection, variable definitions, collection instruments, and operative
      design and analytical procedures for the National Survey Violence Against Women
      in Mexico. MATERIAL AND METHODS: A complex (two-step) cross-sectional study was
      designed and the qualitative design was carried out using in-depth interviews and
      participant observation in health care units. RESULTS: We obtained for the
      quantitative study a total of 26 240 interviews in women users of health services
      and 2 636 questionnaires for health workers; the survey is representative of the
      32 Mexican states. For the qualitative study 26 in-depth interviews were
      conducted with female users and 60 interviews with health workers in the States
      of Quintana Roo, Coahuila and the Federal District.

PMID- 16884172
TI  - Comparing isoflurane with tribromoethanol anesthesia for echocardiographic
      phenotyping of transgenic mice.
AB  - Cardiac phenotyping of transgenic mice typically requires anesthesia. Chemical
      grade tribromoethanol (TBE) is commonly used for this purpose due to its
      relatively short duration of action, modest cardiodepressive effects, and its
      noncontrolled status. In the present study, we used both genders of C57BL/6;C3H
      Tg(Slc8a1)hKdp transgenic (TG) mice and C57BL/6;C3H wild-type (WT) mice to
      evaluate isoflurane (ISF) as a pharmaceutical-grade alternative to TBE for
      echocardiography and electrocardiography. Baseline target physiologic heart rates
      (beats per minute) were established by use of telemetry as 544 +/- 10 in WT mice
      and 580 +/- 21 in TG mice. TG and WT animals were anesthetized with either 0.8%
      to 1% inhalational ISF or 250 mg/kg intraperitoneal TBE. The following parameters
      were measured or calculated according to the previously defined physiologic heart
      rates: end diastolic and systolic dimensions; posterior wall and ventricular
      septal thicknesses; left ventricular mass, aortic ejection times; left
      ventricular fractional shortening; velocity of circumferential fiber shortening;
      and left ventricular ejection fraction. No significant difference between
      anesthetics was found for any measured cardiac parameters. However, the time
      required for data acquisition was significantly shorter for ISF (10 min) than for
      TBE (14 min). This study demonstrates that comparable echocardiographic results
      can be obtained at higher throughput by use of pharmaceuticalgrade ISF than with
      chemical-grade TBE.

PMID- 16884173
TI  - Renal infarction and immune-mediated glomerulonephritis in sheep (Ovis aries)
      chronically implanted with indwelling catheters.
AB  - Microbial infections are common sequelae in humans and animals implanted with
      long-term intravascular catheters. Understanding the pathophysiology of
      infectious morbidity is critical to improving quality of care in catheterized
      subjects. Here, we describe findings in 6 clinically healthy, male sheep
      implanted with indwelling aortic or cardiac catheters for 6 to 10 mo. We isolated
      multiple bacterial species including Serratia spp., Enterobacter agglomerans,
      Eschericia coli, Klebsiella oxytoca, and K. pneumoniae in aerobic cultures from
      catheter tips. Although sheep were clinically asymptomatic, 1 or both kidneys
      from all animals contained wedge-shaped infarcts of varying size and number.
      Microscopic examination revealed (a) marked fibrosis with mild inflammatory cell
      infiltrate consistent with chronic foreign body reaction around catheters; (b)
      moderate to severe, diffuse, subacute to chronic membranoproliferative
      glomerulonephritis and mild, multifocal chronic interstitial nephritis; and (c)
      mesangial immune-complex deposition as demonstrated by direct immunofluorescence
      technique. The finding of bacterial colonization of catheters together with
      chronic glomerulonephritis and immune-complex deposits in kidneys in clinically
      asymptomatic sheep underscores the need for close microbiologic monitoring of
      catheter implants and assessment of kidney function in animals instrumented for
      long-term vascular access.

PMID- 16884174
TI  - Concentrations of isoflavones in macaques consuming standard laboratory monkey
      diet.
AB  - The soy isoflavones genistein and daidzein, as well as the daidzein metabolite
      equol, have structural similarities to mammalian estrogens and bind with varying
      affinity to both known subtypes of the estrogen receptor. Consequently,
      prospective studies in both humans and animals have begun to evaluate the
      potential effects of isoflavones on estrogen receptor-mediated phenomena.
      However, many diets of laboratory-housed animals derive their protein from soy
      and thus likely contain substantial quantities of isoflavones. Exposing
      experimental subjects to these isoflavones via such diets could confound studies,
      particularly those evaluating the effects of estrogen or estrogen-like ligands.
      The aim of this study was to compare the levels of circulating concentrations of
      isoflavones and their metabolites in monkeys fed either a soy-free diet, a soy
      based diet providing 130 mg of isoflavone (daidzein, genistein, and glycitein
      aglycon equivalents) daily, or a commercially available 'chow' diet containing an
      unspecified amount of soybean meal. Animals consuming the commercial diet had
      serum concentrations of daidzein, genistein, and glycitein that were
      significantly higher than those of animals fed a soy-free diet but similar to
      those of monkeys fed a soybased diet formulated to be high in isoflavones.
      Notably, animals fed the commercial diet also had serum equol concentrations that
      were similar to or, in some cases, in excess of serum concentrations in the
      animals fed the soy diet. These data argue for the use of soy-free diets in
      studies investigating estrogenic effects on physiologic or behavioral endpoints.

PMID- 16884175
TI  - Improving murine health surveillance programs with the help of on-site enzyme
      linked immunosorbent assay.
AB  - Timely and accurate detection of murine pathogens is essential in contemporary
      biomedical research. Cost, accuracy, and reproducibility of test results are
      frequent concerns when initiating an on-site serology program. This study was
      conducted to evaluate the advantages of on-site serology performed by enzyme
      linked immunosorbent assay (ELISA) versus pathogen surveillance conducted off
      site by a commercial vendor. We divided 92 sentinel mouse serum samples and
      tested them in parallel for a panel of 10 murine pathogens at our institution and
      by an off-site vendor. On-site testing was performed with commercially available
      test kits and according to the kit manufacturer's directions, whereas serum
      samples for off-site testing were prepared according to the vendor's
      specifications. Results from the 2 testing strategies were compared, and a good
      beyond- chance level of agreement was demonstrated by means of the kappa test
      (kappa = 0.86). The turn-around time between sample preparation and results
      availability for on-site ELISA was 16 h versus 72 h for off-site testing. On-site
      ELISA demonstrated considerable cost reduction, ranging from 15.10% to 43.33%
      depending on the number of agents being tested. This study demonstrates the
      accuracy and time- and cost-effectiveness of on-site ELISA as well as its
      potentially valuable role in achieving more timely and efficient disease
      surveillance and control programs in contemporary biomedical research facilities.

PMID- 16884176
TI  - Multimodal approach to treatment for control of fur mites.
AB  - Ectoparasites pose numerous research, health, and management problems for
      researchers and institutions. Our facility management experience was complicated
      by recurrence of murine fur mite (Radfordia affinis) infestation after several
      rounds of single-mode fur mite treatment with dichlorvos in the cage bedding.
      Subsequently, we successfully eradicated the fur mites using a multidrug
      therapeutic protocol. Over an 8-wk treatment period, 2 applications of topical
      selamectin were administered in conjunction with amitraz- and fipronil-treated
      nestlets changed weekly. Mice tolerated the therapy well with no side effects
      noted, and to date there has been no recrudescence. To our knowledge, this report
      is the first to describe combined use of these specific therapeutic agents to
      control fur mite infestation in laboratory mice.

PMID- 16884177
TI  - The laboratory animal boards study group: A multifaceted tool for preparation for
      the American College for Laboratory Medicine board examination.
AB  - Preparation for the specialty board examination for the American College of
      Laboratory Animal Medicine (ACLAM) is an intensive process that is facilitated by
      geographic regions where many people studying for the exam are located in close
      proximity. However, many people work at institutions that are distant from these
      'study centers'. Approximately 10 y ago, the Laboratory Animal Boards Study Group
      (LABSG) online journal club was established to provide a forum for journal review
      for examination preparation. Over the years, the mission of this group has
      expanded to include practice examinations and practicals, questions from common
      resources, and summaries and questions from common laboratory animal science
      journals. These study aids are beneficial for those preparing for the ACLAM
      certification examination. They are also beneficial for those preparing for the
      technician and manager certification examinations offered by the American
      Association for Laboratory Animal Science (AALAS). This article is intended to be
      an introduction to the variety of study aids available through the LABSG online
      journal review club and the LABSG web page (www.labsg.org). It also provides
      details on the demographics of participants and an exploration of how this
      resource enhances examination preparation.

PMID- 16884178
TI  - Assessment of an intraprostatic injection technique through a perineal approach
      in macaques.
AB  - We developed a surgical procedure for accessing the prostate gland of the
      cynomolgus monkey (Macaca fascicularis) through the perineal cavity. The
      procedure can be used for direct injection of compounds into the prostate gland
      and (or) for the collection of biopsies. The rationale for developing this
      technique at our site was the need for precise injection into the gland with a
      low probability of error, as the compound tested in a subsequent study required
      prostate-specific antigen for activation. A perianal incision was made
      approximately 1 cm ventral to the anus, and the muscle and subcutaneous tissue
      were bluntly dissected between the urethra and the rectum. The prostate gland was
      easily visualized after dissection, and could be grasped gently by the capsule
      and exteriorized through the incision, thus allowing easy access to the prostate
      for study purposes. On the basis of mock injections with methylene blue dye and
      gross observation of prostate tissue at necropsies immediately after injection,
      we recommend that 2 injections be given per lobe of prostate, and injections
      should be to a depth of 2 to 3 mm to provide uniform distribution of injected
      compounds. To minimize back pressure and leakage from the injection site, a
      smallgauge needle (23-27 gauge) should be used and the needle held in place for
      approximately 30 s before withdrawal. Injection volumes 64 mul per g prostate or
      less did not cause the back flow of methylene blue dye into the seminal vesicles.

PMID- 16884179
TI  - Use of human nasal cannulas during bronchoscopy procedures as a simple method for
      maintaining adequate oxygen saturation in pigtailed macaques (Macaca nemestrina).
AB  - Rising concerns over respiratory illnesses caused by agents such as avian
      influenza viruses and SARS coronavirus have prompted intensive research efforts
      and the resurgence of nonhuman primates as models for these human diseases. In
      the context of studying influenza infection and vaccine development, serial
      bronchoscopic procedures, including bronchial brush biopsies and bronchoalveolar
      lavage, were performed in pigtailed macaques (Macaca nemestrina). The possible
      need for oxygen supplementation during these procedures was anticipated because
      of the size of the animals relative to the 5-mm bronchoscope. We therefore
      monitored oxyhemoglobin saturation, a measure of arterial blood oxygen content,
      before and after insertion of the bronchoscope, during bronchoalveolar lavage,
      and after initiation of oxygen supplementation. Although more data are required
      to draw definitive conclusions, our findings suggested the need for oxygen
      supplementation during such procedures in nonhuman primates, despite the fact
      that human patients undergoing bronchoscopy and lavage do not routinely get
      oxygen unless they are already compromised. Our data also suggested that the need
      for supplementation could not be predicted from simple parameters such as size of
      the animal, presence of respiratory clinical signs, or experimental treatment.
      Finally, we show a simple and cost-effective method of using human nasal cannulas
      for delivering oxygen to pigtailed macaques during bronchoscopic procedures, and
      we believe that, after further testing, this method could be used safely and
      effectively in other nonhuman primate species.

PMID- 16884180
TI  - Ultrasound-guided collection of amniotic fluid in pregnant rats.
AB  - Here we present an echographic method to withdraw amniotic fluid from pregnant
      rats. The method could be an alternative to the surgical amniotic fluid
      collection methods used currently. On day 18 of gestation, pregnant Sprague
      Dawley rats underwent amniotic sac puncture by either surgical procedure or
      echographically guided method. This study evaluated the effect of the 2
      collection procedures on parturition day, number of pups per litter, and weight
      of newborns compared with those of a control group without any fluid collection.
      These parameters did not differ statistically across groups. However, the
      echographically guided method did not require surgery or postsurgical recovery
      and was therefore advantageous from the perspective of animal use. Moreover
      ultrasound-guided collection allows experimental designs that require collection
      of multiple samples from the same animal during a single pregnancy.

PMID- 16884181
TI  - Breath-hold device for laboratory rodents undergoing imaging procedures.
AB  - The increased use in noninvasive imaging of laboratory rodents has prompted
      innovative techniques in animal handling. Lung imaging of rodents can be a
      difficult task because of tissue motion caused by breathing, which affects image
      quality. The use of a prototype flat-panel computed tomography unit allows the
      acquisition of images in as little as 2, 4, or 8 s. This short acquisition time
      has allowed us to improve the image quality of this instrument by performing a
      breath-hold during image acquisition. We designed an inexpensive and safe method
      for performing a constant-pressure breath-hold in intubated rodents. Initially a
      prototypic manual 3-way valve system, consisting of a 3-way valve, an air
      pressure regulator, and a manometer, was used to manually toggle between the
      ventilator and the constant-pressure breath-hold equipment. The success of the
      manual 3-way valve system prompted the design of an electronically actuated valve
      system. In the electronic system, the manual 3-way valve was replaced with a
      custom designed 3-way valve operated by an electrical solenoid. The electrical
      solenoid is triggered by using a hand-held push button or a foot pedal that is
      several feet away from the gantry of the scanner. This system has provided
      improved image quality and is safe for the animals, easy to use, and reliable.

PMID- 16884183
TI  - Urolithiasis and transitional cell carcinoma of the bladder in a Wistar rat.
AB  - Urolithiasis and carcinoma of the urinary bladder are generally uncommon in rats.
      In particular, spontaneous urolithiasis and carcinoma of the bladder in young
      rats has not yet been reported. Our case concerns the unexpected finding of
      urolithiasis of the bladder and left kidney of an apparently healthy 4-mo-old
      male Wistar rat. The bladder was filled with 28 white, round to oval calculi of
      various sizes. The kidney presented a single unevenly shaped calculus in the
      pelvis. Histology revealed, in addition to urolithiasis, a grade II papillary
      transitional cell carcinoma of the bladder, with muscle invasion and neoplastic
      extension to the left renal pelvic epithelium. No previous experimental procedure
      or dietetic manipulation had occurred, which could be held responsible for these
      findings. These unusual findings indicate that, unknown to researchers,
      unapparent factors can affect the health status of even relatively young
      experimental animals. Asymptomatic disease, such as the unknown presence of a
      tumor, potentially can affect many parameters and thus influence research
      results.

PMID- 16884182
TI  - Refractometry for quality control of anesthetic drug mixtures.
AB  - Injectable anesthetic drugs used in rodents are often mixed and further diluted
      to increase the convenience and accuracy of dosing. We evaluated clinical
      refractometry as a simple and rapid method of quality control and mixing error
      detection of rodent anesthetic or analgesic mixtures. Dilutions of ketamine,
      xylazine, acepromazine, and buprenorphine were prepared with reagent-grade water
      to produce at least 4 concentration levels. The refraction of each concentration
      then was measured with a clinical refractometer and plotted against the
      percentage of stock concentration. The resulting graphs were linear and could be
      used to determine the concentration of single-drug dilutions or to predict the
      refraction of drug mixtures. We conclude that refractometry can be used to assess
      the concentration of dilutions of single drugs and can verify the mixing accuracy
      of drug combinations when the components of the mixture are known and fall within
      the detection range of the instrument.

PMID- 16884184
TI  - Measurement of the thermodynamics of the hydrated dimer and trimer of sulfuric
      acid.
AB  - We report measurements of the equilibrium constants, K(p), for the water mediated
      clustering of two and three sulfuric acid molecules for atmospheric temperatures
      and relative humidities. Limits for K(p) for the formation of the sulfuric acid
      tetramer and higher clusters as well as the kinetics of small sulfuric acid
      cluster growth are also presented. These results put strong constraints on the
      rate of nucleation in the atmosphere via the H(2)SO(4)/H(2)O neutral mechanism.
      We show that the neutral nucleation of H(2)SO(4) and H(2)O is slower than ion
      induced nucleation of H(2)SO(4) and H(2)O for most conditions found in the middle
      and upper troposphere. These laboratory-based upper limits to the nucleation
      rates are also much lower than the predictions of the liquid drop model/classical
      nucleation theory.

PMID- 16884185
TI  - Exploration of basis set issues for calculation of intermolecular interactions.
AB  - The ab initio calculation of intermolecular interactions requires a large basis
      set to describe systems with dominant dispersion interaction accurately. This
      paper focuses on calculation of intermolecular bonding energies of weakly bound
      systems within the supermolecular method and on issues related to the choice of a
      basis set for these calculations, in particular size of the basis set, efficiency
      of 2-electron integral codes, basis set superposition error (BSSE), and the
      linear dependence of basis functions. In an attempt to find more efficient basis
      sets for calculations of intermolecular interactions, standard basis sets (10s
      Huzinaga, 6-311G**, cc-pV6Z), or their parts, are extended (tessellated) by a set
      of off-centered, s or p functions, symmetrically placed around the nuclei.
      Standard basis sets (10s Huzinaga, 6-311G**, cc-pVXZ, aug-cc-pVXZ, X = D, T, Q,
      5, 6) are also augmented by sets of atom-centered, higher angular momentum
      functions (p, d, f). The distance from the nucleus of tessellating functions and
      orbital exponents of tessellating and augmenting functions are optimized with
      respect to the BSSE-corrected bonding energy at the MP2 or UCCSD level of theory.
      The two approaches are tested on the model systems with dominant dispersion
      interactions (3)H(2), (CH(4))(2), and Ne(2), and their efficiency is compared.
      Both tessellation and augmentation are successful in describing the
      intermolecular interactions of these model systems, with augmentation being more
      efficient. Our results draw attention to the linear dependence problems
      inevitably present in accurate calculations and confirm the need for underlying
      standard basis sets that provide good descriptions of core and valence electrons
      for the tessellation and augmentation approaches to be reliable.

PMID- 16884186
TI  - Thermodynamic analysis of the chemical exchange of beta-phosphorylated cyclic
      nitroxides by using two-dimensional (temperature versus magnetic field)
      simulation of ESR spectra: the impact of labile solvent-solute interactions on
      molecular dynamics.
AB  - A complete thermodynamic characterization of the chair-to-chair interconversion
      in beta-diphosphorylated piperidine-N-oxyl radicals was achieved by means of the
      analysis of temperature-dependent ESR spectra. A new two-dimensional simulation
      method was developed with the coordinates temperature and magnetic field, in
      which the entire set of spectra was simulated simultaneously by adjusting the
      coefficients in the power expansion, giving the temperature-dependent ESR
      parameters and the thermodynamic and kinetic parameters determining the site
      populations and exchange rates, respectively. The new method promotes elimination
      of the ambiguities inherent in the spectroscopic determination of thermodynamic
      parameters. Labile solvent-solute interactions can strongly influence the
      chemical exchange, producing a complex network of symmetric and asymmetric
      interconversions. The solvent dependence of magnetic relaxation was also
      analyzed.

PMID- 16884188
TI  - Vibrational energy relaxation of polyatomic molecules in liquid solution via the
      linearized semiclassical method.
AB  - Vibrational energy relaxation (VER) of polyatomic, as opposed to diatomic,
      molecules can occur via different, often solvent assisted, intramolecular and/or
      intermolecular pathways. In this paper, we apply the linearized semiclassical
      (LSC) method for calculating VER rates in the prototypical case of a rigid,
      symmetrical and linear triatomic molecule (A-B-A) in a monatomic liquid. Starting
      at the first excited state of either the symmetric or asymmetric stretches, VER
      can occur either directly to the ground state or indirectly via intramolecular
      vibrational relaxation (IVR). The VER rate constants for the various pathways are
      calculated within the framework of the Landau-Teller formalism, where they are
      expressed in terms of two-time quantum-mechanical correlation functions. The
      latter are calculated by the LHA-LSC method, which puts them in a "Wignerized"
      form, and employs a local harmonic approximation (LHA) in order to compute the
      necessary multidimensional Wigner integrals. Results are reported for the LHL/Ar
      model of Deng and Stratt [J. Chem. Phys. 2002, 117, 1735], as well as for CO(2)
      in liquid argon and in liquid neon. The LHA-LSC method is shown to give rise to
      significantly faster VER and IVR rates in comparison to the classical treatment,
      particularly at lower temperatures. We also find that the type and extent of the
      quantum rate enhancement is strongly dependent on the particular VER pathway.
      Finally, we find that the classical and semiclassical treatments can give rise to
      opposite trends when it comes to the dependence of the VER rates on the solvent.

PMID- 16884187
TI  - Dynamic solvation in imidazolium-based ionic liquids on short time scales.
AB  - Steady-state and time-resolved Stokes shift data for the probe coumarin 153 in
      two imidazoles, six imidazolium-based ionic liquids, and several other solvents
      are presented. These results are consistent with our original suggestion (J.
      Phys. Chem. B 2004, 108, 10245-10255) that initial solvation is dominated by the
      organic moiety of the ionic liquid, and they show that for the imidazole-based
      liquids initial solvation is in all cases very rapid. Solvation by
      methylimidazole and butylimidazole is complete in 100 ps, and all of the
      imidazolium ionic liquids demonstrate similarly rapid initial solvation. Owing to
      the importance of determining the amount of initial solvation that is missed in a
      given experiment with finite time resolution, we discuss a method of estimating
      the intramolecular contribution to the reorganization energy. This method yields
      2068 cm(-1) and is compared with an alternative method.

PMID- 16884189
TI  - Quasi-classical trajectory calculations analyzing the role of bending mode
      excitations of methane in the Cl + CH4 reaction.
AB  - The effects of the methane torsional (nu(2)), umbrella (nu(4)), and the
      combination nu(2)+nu(4) bending mode excitations on the reactivity and dynamics
      of the gas-phase Cl + CH(4) --> HCl + CH(3) reaction were analyzed. Quasi
      classical trajectory (QCT) calculations, including corrections to avoid zero
      point energy leakage along the trajectories, were used on an analytical potential
      energy surface previously developed by our group. With respect to the reactivity,
      we found that excitation of either bending mode independently gave similar
      increases in the reactivity, while the increase observed upon excitation of both
      modes was larger than the sum of the effect of exciting them independently. Both
      results agree with recent experimental measures. With respect to the dynamics
      (rotovibrational and angular distributions of the products), the two bending
      modes and their combination gave very similar pictures, reproducing the
      experimental behavior. The satisfactory agreement obtained with a great variety
      of experimental data (always qualitatively acceptable and sometimes even
      quantitatively) of the present QCT study lends confidence to the potential energy
      surface constructed by our group.

PMID- 16884190
TI  - Cation/anion recognition by a partially substituted lower rim calix[4]arene
      hydroxyamide, a ditopic receptor.
AB  - The complexation ability of a partially substituted lower rim calix[4]arene
      hydroxyamide derivative, 25,27-bis[N-(2-hydroxy-1,1-bishydroxymethylethyl)amino-
      carbonylmethoxy]calix[4]arene-26,28-diol, 1, for cations and anions was
      investigated through (1)H NMR, conductometry, spectrophotometry, and calorimetry
      in dipolar aprotic media. (1)H NMR studies of 1 in the deuterated solvents
      (acetonitrile, methanol, and dimethylsulfoxide) reflect ligand-solvent
      interactions in methanol and dimethylsulfoxide. As far as the cations are
      concerned, a selectivity peak is found when standard Gibbs energies of
      complexation of 1 with cations (alkaline-earth, zinc, and lead) are plotted
      against corresponding data for cation hydration. This finding reflects the key
      role played by the desolvation and binding processes in the overall complexation
      of this receptor and these cations in acetonitrile. This is also interpreted in
      terms of enthalpy and entropy data. Factors such as, the nature and the
      arrangement of donor atoms in the hydrophilic cavity of the ligand on cation
      complexation process, are discussed. This paper also addresses anion complexation
      processes. It is found that 1 interacts through hydrogen bond formation with
      fluoride, dihydrogen phosphate, and pyrophosphate in acetonitrile and N,N
      dimethylformamide. The thermodynamics associated with these processes is fully
      discussed taking into account literature data involving calix[4]pyrroles and
      these anions in these solvents. Previous work regarding the water solubility of
      these ligands is discussed. It is concluded that 1 behaves as a ditopic ligand in
      dipolar aprotic media.

PMID- 16884191
TI  - Single crystals of L-O-serine phosphate X-irradiated at low temperatures: EPR,
      ENDOR, EIE, and DFT studies.
AB  - Single crystals of the phosphorylated amino acid L-O-serine phosphate were X
      irradiated and studied at 10 K and at 77 K using EPR, ENDOR, and EIE techniques.
      Two radicals, R1(10 K) and R1(77 K), were detected and characterized as two
      different geometrical conformations of the protonated reduction product >CH
      C(OH)(2). R1(10 K) is only observed after irradiation at 10 K, and upon heating
      to 40 K, R1(10 K) transforms rapidly and irreversibly into R1(77 K). The
      transition from R1(10 K) to R1(77 K) strongly increases the isotropic hyperfine
      coupling of the C-CH(beta) coupling (Delta = 32 MHz) and the major C-OH(beta)
      coupling (Delta = 47 MHz), in sharp contrast to the their much reduced
      anisotropic hyperfine couplings after the transition. An umbrella-like inversion
      of the carboxylic acid center, accompanied by minor geometrical adjustments,
      explains the changes of these observed isotropic and anisotropic couplings. DFT
      calculations were done on the reduced and protonated L-O-serine phosphate radical
      at the B3LYP/6-311+G(2df,p)//B3LYP/6-31+G(d) level of theory in order to support
      the experimental observations. Two different conformations of the anion radical,
      related by an inversion at the carboxylic center, could be found within the
      single molecule partial energy-optimization scheme. These two conformations
      reproduce the experimental hyperfine couplings from radicals R1(10 K) and R1(77
      K). A third radical, radical R2, was observed experimentally at both 10 and 77 K
      and was shown to be due to the decarboxylated L-O-serine phosphate oxidation
      product, a conclusion fully supported from the DFT calculations. Upon thermal
      annealing from 77 to 295 K, radicals R1(77 K) and R2 disappeared and all three
      previously observed room-temperature radicals could be observed. No phosphate
      centered radicals could be observed at any temperatures, indicating that the
      phosphate-ester bond break for one of the room-temperature radicals does not
      occur by dissociative electron capture at the phosphate group.

PMID- 16884192
TI  - Vapor phase near infrared spectroscopy of the hydrogen bonded methanol
      trimethylamine complex.
AB  - The spectroscopy of the vapor phase hydrogen bonded complex formed between
      methanol and trimethylamine has been studied in the near-infrared region. A
      combination band involving one quantum of OH stretch and one quantum of COH bend
      has been observed for the complex. The much less intense first OH-stretching
      overtone transition has been tentatively assigned. This assignment is supported
      by anharmonic oscillator local mode calculations.

PMID- 16884194
TI  - Light-induced electron spin polarization in vanadyl octaethylporphyrin: I.
      Characterization of the excited quartet state.
AB  - Laser flash induced spin-polarized transient electron paramagnetic resonance
      (TREPR) spectra for vanadyl octaethylporphyrin in isotropic and partially ordered
      frozen solutions are presented and compared with corresponding luminescence data.
      The TREPR spectra show well-resolved hyperfine couplings to the vanadium nucleus
      and a multiplet polarization pattern with features typical of zero-field
      splitting (ZFS). The principal values of the vanadium hyperfine coupling tensor
      evaluated from the spectra are 1/3 of the corresponding values found from steady
      state EPR spectra of the ground state. On the basis of these characteristics and
      numerical simulations, the polarization patterns are assigned to the excited
      quartet state. The values of the ZFS parameters of the trip-quartet obtained from
      simulation of the spectra (D = 17.5 mT and E = 1.5 mT) are comparable to those of
      the triplet state of the zinc and free base octaethyl porphyrin. The lifetime of
      the spin polarization is found to be temperature dependent and is essentially the
      same as that of the optical emission. The temperature dependence is rationalized
      using a model in which the decay to the ground state occurs from both the trip
      quartet and trip-doublet, which are in thermal equilibrium even at 15 K. A fit of
      the model to the observed spin polarization lifetimes yields an energy gap of 47
      cm(-1) between the trip-quartet and trip-doublet. It is shown that the spin
      polarization evolves from a multiplet pattern at early times to a net absorptive
      pattern at late times following the laser flash. It is proposed that the
      establishment of thermal equilibrium leads to the evolution of the spin from
      multiplet to net polarization.

PMID- 16884193
TI  - Selective intercalation of Cs+ in the "V"-shaped cavity of a bichromophoric anion
      radical: Cs+ assisted pi-s-pi-delocalization of an electron.
AB  - EPR studies in tetrahydrofuran, reveal that the one electron reduction of 1-(9
      methyl-9H-fluoren-9-yl)-4-methylbenzene via electron transfer from cesium metal
      produces an anion radical that has a large affinity for the cesium cation. The
      affinity of this anion radical for Cs+ is so great that it will actually "suck"
      the Cs+ (but not Na+ or K+) right out of the grasp of 18-crown-6, leading to a
      cation-assisted pi-stacked complex, where the s-orbital of the metal cation is
      simultaneously overlapped with the pi-clouds of the phenyl and fluorenyl
      moieties. At ambient temperature, proton- and cesium-electron coupling constants
      are rapidly (on the EPR time scale) modulated as a result of the simultaneous
      existence of two interconverting conformers having an averaged cesium splitting
      (a(Cs)) of about 1.6 G. The pi-s-pi-electronic coupling can be turned on or off
      via the addition or removal of cesium cations. Analogous pi-s-pi-electronic
      coupling is observed in the 1,4-bis(9-methyl-9H-fluoren-9-yl)benzene-cesium
      system.

PMID- 16884195
TI  - Light-induced electron spin polarization in vanadyl octaethylporphyrin: II.
      Dynamics of the excited states.
AB  - The dynamics of the low-lying excited states of vanadyl octaethylporphyrin
      (OEPVO) in frozen solution is investigated by transient electron paramagnetic
      resonance (TREPR). The observation of spin-polarized TREPR spectra from the
      lowest excited trip-quartet state of OEPVO, reported in the preceding paper,
      opens a new avenue for investigation of the excited states of such molecules.
      Here, a model based on the back-and-forth transitions between the trip-quartet
      and trip-doublet states is developed and used to explain the time dependence of
      the low-temperature laser flash-induced electron spin polarization of OEPVO. At
      early times, the TREPR spectra show predominantly multiplet polarization, whereas
      strong net polarization develops at later times. An analysis of the time
      dependence reveals two well-separated processes: (i) fast evolution of the
      polarization from the multiplet pattern to the net absorptive pattern and (ii)
      very slow decay of the net polarization. Both processes are temperature dependent
      and are faster at higher temperature. All of these observed features can be
      reproduced, and the experimental data can be simulated within the framework of
      the model. For simplicity, only the two nearly degenerate orbital states
      resulting from the a(1) --> e triplet excitation of the porphyrin are considered.
      Each of these is split into a trip-doublet and trip-quartet giving a total of
      four low-lying excited states. Transitions between the trip-doublet and trip
      quartet states are assumed to be governed by spin-orbit coupling, which mixes the
      four low-lying states. It is known that following light excitation, the molecule
      initially decays to the lowest trip-doublet state and then to the trip-quartet
      state. In agreement with the observed TREPR spectra, the model predicts that this
      decay results in predominantly multiplet polarization of the trip-quartet.
      However, a small amount of net polarization is also predicted due to the spin
      selectivity associated with the Zeeman interaction. Because the energy gap
      between the trip-doublet and trip-quartet states is small, back-and-forth
      electronic transitions between the trip-doublet and trip-quartet are expected to
      occur as thermal equilibrium is established. The model predicts that it is these
      transitions that lead to the observed evolution of the initial multiplet
      polarization to net absorptive polarization.

PMID- 16884196
TI  - Infrared spectroscopy of hydrogen-bonded 2-fluoropyridine-water clusters in
      supersonic jets.
AB  - The hydrogen-bonded clusters of 2-fluoropyridine with water were studied
      experimentally in a supersonic free jet and analyzed with molecular orbital
      calculations. The IR spectra of 2-fluoropyridine-(H2O)(n) (n = 1 to 3) clusters
      were observed with a fluorescence detected infrared depletion (FDIR) technique in
      the OH and CH stretching vibrational regions. The frequencies of OH stretching
      vibrations show that water molecules bond to the nitrogen atom of 2
      fluoropyridine in the clusters. The hydrogen-bond formation between aromatic CH
      and O was evidenced in the 1:2 and 1:3 clusters from the experimental and
      calculated results. The overtone vibrations of the OH bending mode in hydrogen
      bonded water molecules appear in the IR spectra, and these frequencies become
      higher with the increase of the number of water molecules in the clusters. The
      band structure of the IR spectra in the CH stretching region changes depending on
      the number of coordinating water molecules.

PMID- 16884197
TI  - Quantum tunneling in the midrange vibrational fundamentals of tropolone.
AB  - The Fourier transform infrared spectrum of tropolone(OH) vapor in the 1175-1700
      cm(-1) region is reported at 0.0025 and 0.10 cm(-1) spectral resolutions. The 12
      vibrational fundamentals in this region of rapidly rising vibrational state
      density are dominated by mixtures of the CC, CO, CCH, and COH internal
      coordinates. Estimates based on the measurement of sharp Q branch peaks are
      reported for 11 of the spectral doublet component separations DS(v) = |Delta(v)
      +/- Delta(0)|. Delta(0) = 0.974 cm(-1) is the known zero-point splitting, and
      three a(1) modes show tunneling splittings Delta(v) approximately Delta(0), four
      b(2) modes show splittings Delta(v) approximately 0.90Delta(0), and the remaining
      four modes show splittings Delta(v) falling 5-14% from Delta(0.) Significantly,
      the splitting for the nominal COH bending mode nu(8) (a(1)) is small, that is,
      10% from Delta(0). Many of the vibrational excited states demonstrate strong
      anharmonic behavior, but there are only mild perturbations on the tautomerization
      mechanism driving Delta(0). The data suggest, especially for the higher frequency
      a(1) fundamentals, the onset of selective intramolecular vibrational energy
      redistribution processes that are fast on the time scale of the tautomerization
      process. These appear to delocalize and smooth out the topographical
      modifications of the zero-point potential energy surface that are anticipated to
      follow absorption of the nu(v) photon. Further, the spectra show the propensity
      for the Delta(v) splittings of b(2) and other complex vibrations to be damped
      relative to Delta(0).

PMID- 16884198
TI  - Uptake of HNO3 on hexane and aviation kerosene soots.
AB  - The uptake of HNO(3) on aviation kerosene (TC-1) soot was measured as a function
      of temperature (253-295 K) and the partial pressure of HNO(3), and the uptake of
      HNO(3) on hexane soot was studied at 295 K and over a limited partial pressure of
      HNO(3). The HNO(3) uptake was mostly reversible and did not release measurable
      amounts of gas-phase products such as HONO, NO(3), NO(2) or N(2)O(5). The heat of
      adsorption of HNO(3) on soot was dependent on the surface coverage. The isosteric
      heats of adsorption, Delta(0)H(isosteric), were determined as a function of
      coverage. Delta(0)H(isosteric) values were in the range -16 to -13 kcal mol(-1).
      The heats of adsorption decrease with increasing coverage. The adsorption data
      were fit to Freundlich and to Langmuir-Freundlich isotherms. The heterogeneity
      parameter values were close to 0.5, which suggested that a HNO(3) molecule can
      occupy two sites on the surface with or without being dissociated and that the
      soot surface could be nonuniform. Surface FTIR studies on the interaction of soot
      with HNO(3) did not reveal formation of any minor product such as organic nitrate
      or nitro compound on the soot surface. Using our measured coverage, we calculate
      that the partitioning of gas-phase nitric acid to black carbon aerosol is not a
      significant loss process of HNO(3) in the atmosphere.

PMID- 16884199
TI  - Mechanism of C-O activation in dimethoxyethane cationic iron complexes.
AB  - The fragmentation mechanism of iron complexes bearing a bidentate ligand,
      dimethoxyethane (CH(3)OCH(2)CH(2)OCH(3), labeled as DXE) has been investigated by
      means of FT-ICR mass spectrometry (ion-molecule reactions) and infrared
      multiphoton dissociation spectroscopy. Two possible reaction mechanisms were
      envisioned for the Fe(DXE)(+) + DXE reaction, leading to the formation of the
      Fe(CH(2)O)(DXE)(+) ion. The two mechanisms differ in the nature of the neutral
      molecules formed: CH(3)OC(2)H(5) or CH(2)=CH(2) + CH(3)OH. The combination of ion
      molecule reactions, thermochemistry considerations, and IRMPD spectra leads us to
      suggest that the mechanism involves successive elimination of the neutrals
      CH(2)=CH(2) and CH(3)OH, the first step of the mechanism being the insertion of
      the iron atom in the O-C(central) bond.

PMID- 16884200
TI  - Chemical composition of secondary organic aerosol formed from the photooxidation
      of isoprene.
AB  - Recent work in our laboratory has shown that the photooxidation of isoprene (2
      methyl-1,3-butadiene, C(5)H(8)) leads to the formation of secondary organic
      aerosol (SOA). In the current study, the chemical composition of SOA from the
      photooxidation of isoprene over the full range of NO(x) conditions is
      investigated through a series of controlled laboratory chamber experiments. SOA
      composition is studied using a wide range of experimental techniques:
      electrospray ionization-mass spectrometry, matrix-assisted laser desorption
      ionization-mass spectrometry, high-resolution mass spectrometry, online aerosol
      mass spectrometry, gas chromatography/mass spectrometry, and an iodometric
      spectroscopic method. Oligomerization was observed to be an important SOA
      formation pathway in all cases; however, the nature of the oligomers depends
      strongly on the NO(x) level, with acidic products formed under high-NO(x)
      conditions only. We present, to our knowledge, the first evidence of particle
      phase esterification reactions in SOA, where the further oxidation of the
      isoprene oxidation product methacrolein under high-NO(x) conditions produces
      polyesters involving 2-methylglyceric acid as a key monomeric unit. These
      oligomers comprise approximately 22-34% of the high-NO(x) SOA mass. Under low
      NO(x) conditions, organic peroxides contribute significantly to the low-NO(x) SOA
      mass (approximately 61% when SOA forms by nucleation and approximately 25-30% in
      the presence of seed particles). The contribution of organic peroxides in the SOA
      decreases with time, indicating photochemical aging. Hemiacetal dimers are found
      to form from C(5) alkene triols and 2-methyltetrols under low-NO(x) conditions;
      these compounds are also found in aerosol collected from the Amazonian
      rainforest, demonstrating the atmospheric relevance of these low-NO(x) chamber
      experiments.

PMID- 16884201
TI  - Kinetics of triscarbonato uranyl reduction by aqueous ferrous iron: a theoretical
      study.
AB  - Uranium is a pollutant whose mobility is strongly dependent on its oxidation
      state. While U(VI) in the form of the uranyl cation is readily reduced by a range
      of natural reductants, by contrast complexation of uranyl by carbonate greatly
      reduces its reduction potential and imposes increased electron transfer (ET)
      distances. Very little is known about the elementary processes involved in
      uranium reduction from U(VI) to U(V) to U(IV) in general. In this study, we
      examine the theoretical kinetics of ET from ferrous iron to triscarbonato uranyl
      in aqueous solution. A combination of molecular dynamics (MD) simulations and
      density functional theory (DFT) electronic structure calculations is employed to
      compute the parameters that enter into Marcus' ET model, including the
      thermodynamic driving forces, reorganization energies, and electronic coupling
      matrix elements. MD simulations predict that two ferrous iron atoms will bind in
      an inner-sphere fashion to the three-membered carbonate ring of triscarbonato
      uranyl, forming the charge-neutral ternary Fe(2)UO(2)(CO(3))(3)(H(2)O)(8)
      complex. Through a sequential proton-coupled electron-transfer mechanism (PCET),
      the first ET step converting U(VI) to U(V) is predicted by DFT to occur with an
      electronic barrier that corresponds to a rate on the order of approximately 1 s(
      1). The second ET step converting U(V) to U(IV) is predicted to be significantly
      endergonic. Therefore, U(V) is a stabilized end product in this ET system, in
      agreement with experiment.

PMID- 16884202
TI  - Saturated hydrocarbon-benzene complexes: theoretical study of cooperative CH/pi
      interactions.
AB  - High-level ab initio calculations at the CCSD(T)/aug-cc-pVTZ//MP2/aug(d,p)-6
      311G(d,p) level were employed to investigate the cooperative CH/pi effects
      between the pi face of benzene and several modeled saturated hydrocarbons,
      propane, isobutane, cyclopropane, cyclobutane, cyclopentane, cyclohexane,
      cyclopentane, cyclooctane, and bicyclo[2.2.2]octane. In all cases, multiple C-H
      groups (2-4) are found to interact with the pi face of benzene, with one C-H
      group pointing close to the center of the benzene ring. The geometries of these
      complexes are governed predominantly by electrostatic interaction between the
      interacting systems. The calculated interaction energies (10-14 kJ mol(-1)) are 2
      3 times larger than that of the prototypical methane-benzene complex. The trends
      of geometries, interaction energies, binding properties, as well as electron
      density topological properties were analyzed. The calculated interaction energies
      correlate well with the polarizabilities of the hydrocarbons. AIM analysis
      confirms the hydrogen-bonded nature of the CH/pi interactions. Significant
      changes in proton chemical shift and stretching frequency (blue shift) are
      predicted for the ring C-H bond in these complexes.

PMID- 16884203
TI  - Theoretical study of rhenium dinuclear complexes: Re-Re bonding nature and
      electronic structure.
AB  - Four dinuclear rhenium complexes, [Re2Cl8](2-) (1), [Re2(mu-Cl)3Cl6](2-) (2a),
      [Re2(mu-Cl)3Cl6](-) (2b), and [Re2(mu-Cl)2Cl8](2-) (3), were theoretically
      investigated by the CASSCF, MRMP2, SA-CASSCF, and MCQDPT methods. Interesting
      differences in electronic structure and Re-Re bonding nature among these
      complexes are clearly reported here, as follows: In 1, the ground state is the
      1A1g state. The approximate stabilization energies by the sigma, pi, and delta
      bonding interactions are evaluated to be 4.36, 2.89, and 0.52 eV, respectively,
      by the MRMP2 method. In 2a, the ground state is the 2E" state. The approximate
      stabilization energy by two degenerate delta bonding interactions is estimated to
      be 0.36 eV by the MCQDPT method. One delta bonding interaction of 2a is much
      weaker than that of 1, which is discussed in terms of the Re-Re distance and the
      Re oxidation state. In 2b, the ground state is the 1A1' state, of which
      multiconfigurational nature is extremely large unlike that of the 2E" ground
      state of 2a despite similarities between 2a and 2b. In 3, the sigma, pi, and
      delta bonding interactions are not effectively formed between two Re centers. As
      a result, the 1Ag, 3B1u, 5Ag, and 7B1u states are in almost the same energy
      within 0.03 eV. This result is consistent with the paramagnetism of 3
      experimentally reported.

PMID- 16884204
TI  - On the gas phase hydrogen bond complexes between formic acid and hydroperoxyl
      radical. A theoretical study.
AB  - We present a systematic study on the gas-phase hydrogen-bonded complexes formed
      between formic acid and hydroperoxyl radical, which has been carried out by using
      B3LYP and CCSD(T) theoretical approaches in connection with the 6-311+G(2df,2p)
      basis set. For all complexes we have employed the AIM theory by Bader and the NBO
      partition scheme by Weinhold to analyze the bonding features. We have found 17
      stationary points, and 11 of them present a cyclic structure. Their computed
      stabilities vary from 0.3 to 11.3 kcal/mol, depending on several factors, such as
      involvement in the hydrogen bond interaction, the geometrical constraints, and
      the possible concurrence of further effects such as resonance-assisted hydrogen
      bonds or inductive effects. In addition, three stationary points correspond to
      transition structures involving a double proton-transfer process whose features
      are also analyzed.

PMID- 16884205
TI  - Co2+ binding cysteine and selenocysteine: a DFT study.
AB  - In this paper we report structural and energetic data for cysteine and
      selenocysteine in the gas phase and the effect of Co(2+) complexation on their
      properties. Different conformers are analyzed at the DFT/B3LYP level of both
      bound and unbound species. Geometries, vibrational frequencies, and natural
      population analysis are reported and used to understand the activity of these
      species. In particular, we have focused our attention on the role of sulfur and
      selenium in the metal binding process and on the resulting deprotonation of the
      thiol and seleniol functions. From the present calculations we are able to
      explain, both from electronic structure and thermochemical point of views, a
      metal-induced thiol deprotonation as observed in gas-phase experiments. A similar
      process is expected in the case of selenocysteine. In fact, cobalt was found to
      have a preferential affinity with respect to thiolate and selenolate functions.
      This can be related to the observation that only S and Se are able-in thiolate
      and selenolate states-to make a partial charge transfer to the cobalt thus
      forming very stable complexes. Globally, very similar results are found when
      substituting S with Se, and a very small difference in cobalt binding affinity is
      found, thus justifying the use of this substitution in X-ray absorption
      experiments done on biomolecules containing cysteine metal binding pockets.

PMID- 16884206
TI  - EPR and DFT studies of the structure of phosphinyl radicals complexed by a
      pentacarbonyl transition metal.
AB  - Paramagnetic complexes M(CO)5P(C6H5)2, with M = Cr, Mo, W, have been trapped in
      irradiated crystals of M(CO)5P(C6H5)3 (M = Cr, Mo, W) and M(CO)5PH(C6H5)2 (M =
      Cr, W) and studied by EPR. The radiolytic scission of a P-C or a P-H bond,
      responsible for the formation of M(CO)5P(C6H5)2, is consistent with both the
      number of EPR sites and the crystal structures. The g and 31P hyperfine tensors
      measured for M(CO)5P(C6H5)2 present some of the characteristics expected for the
      diphenylphosphinyl radical. However, compared to Ph2P*, the 31P isotropic
      coupling is larger, the dipolar coupling is smaller, and for Mo and W compounds,
      the g-anisotropy is more pronounced. These properties are well predicted by DFT
      calculations. In the optimized structures of M(CO)5P(C6H5)2 (M = Cr, Mo, W), the
      unpaired electron is mainly confined in a phosphorus p-orbital, which conjugates
      with the metal d(xz) orbital. The trapped species can be described as a
      transition metal-coordinated phosphinyl radical.

PMID- 16884208
TI  - Structure and properties of Mn(n), Mn(n)-, and Mn(n)+ clusters (n = 3-10).
AB  - Electronic and geometrical structures of Mn(3)-Mn(10) together with their singly
      negatively and positively charged ions are computed using density functional
      theory with generalized gradient approximation. The ground-state spin
      multiplicities in the neutral series are 16, 21, 4, 9, 6, 5, 2, and 5, for Mn(3)
      Mn(10), respectively. Thus, there is a transition from a ferromagnetic ground
      state to a ferrimagnetic ground state at Mn(5). The energy difference between
      ferrimagnetic and ferromagnetic states in Mn(n) grows rapidly with increasing n
      and exceeds 2 eV in Mn(10). The corresponding change from ferro- to ferrimagnetic
      ground state occurs at Mn(6)(-) and Mn(3)(+) in the anionic and cationic series,
      respectively. Beginning with Mn(6), the ion spin multiplicities differ from that
      of the neutral by +/-1 (i.e., they obey the empirical "+/-1 rule"). We found that
      the energy required to remove an Mn atom is nearly independent of the charge
      state of an Mn(n) cluster and the number of atoms in the cluster, except for
      Mn(3). The results of our calculations are in reasonable agreement with
      experiment, except for the experimental data on the magnetic moments per atom,
      where, in general, we predict smaller values than the experiment.

PMID- 16884207
TI  - Information theoretical approach to single-molecule experimental design and
      interpretation.
AB  - We use Shannon's definition of information to develop a theory to predict a
      photon-counting-based single-molecule experiment's ability to measure the desired
      property. We treat three phenomena that are commonly measured on single
      molecules: spectral fluctuations of a solvatochromic dye; assignment of the
      azimuthal dipole angle; determination of a distance by fluorescence resonant
      energy transfer using Forster's theory. We consider the effect of background and
      other "imperfections" on the measurement through the decrease in information.

PMID- 16884209
TI  - Accurate enthalpies of formation of alkali and alkaline earth metal oxides and
      hydroxides: assessment of the correlation consistent composite approach (ccCA).
AB  - Computing the enthalpies of formation for alkali metal and alkaline earth metal
      oxides (M(x)O) and hydroxides [M(OH)(n)] using the Gaussian-n (Gn) and Weismann-n
      (Wn) ab initio model chemistries is difficult due to an improper treatment of
      core-valence electron correlation effects. Using a new model chemistry called the
      correlation consistent Composite Approach (ccCA), enthalpies of formation were
      determined for eight different alkali/alkaline earth metal oxides and hydroxides.
      Unlike the Gn and Wn model chemistries, which must be modified to properly
      account for core-valence electron correlation, the standard implementations of
      the ccCA provide acceptable results, and all enthalpies of formation obtained
      with the ccCA are within the accepted range of recommended values.

PMID- 16884210
TI  - Bond length alternation and energy band gap of polyyne.
AB  - The bond length alternation (BLA) and energy band gap of polyyne are investigated
      by various first-principles theories, including Hartree-Fock, MP2, hybrid, and
      nonhybrid density functional theories. Both solid-state calculations utilizing
      periodic boundary conditions on polymers and molecular quantum mechanical
      calculations on extra-long oligomers were performed with consistent results. By
      validation on similar linear conjugated polymers, polyacetylene and
      polydiacetylene, the combination of hybrid-DFT schemes, B3LYP//BHandHLYP or
      B3LYP//KMLYP, is shown to give the best predictions for both geometry and band
      gap of polyyne based on available experimental data. We conclude that the best
      estimate of the BLA of polyyne is about 0.13 A and that of the band gap is about
      2.2 eV.

PMID- 16884211
TI  - Hydrogen bonds in imidazolium ionic liquids.
AB  - It is critically important to understand the structural properties of ionic
      liquids. In this work, the structures of cations, anions, and cation-anion ion
      pairs of 1,3-dialkylimidazolium based ionic liquids were optimized systematically
      at the B3LYP/6-31+G level of DFT theory, and their most stable geometries were
      obtained. It was found that there exist only one-hydrogen-bonded ion-pairs in
      single-atomic anion ionic liquids such as [emim]Cl and [emim]Br, while one- and
      two-hydrogen-bonded ion-pairs in multiple atomic anion ionic liquids such as
      [emim]BF(4) and [emim]PF(6) exist. Further studies showed that the cations and
      anions connect each other to form a hydrogen-bonded network in 1,3
      dialkylimidazolium halides, which has been proven by experimental measurement.
      Furthermore, the correlation of melting points and the interaction energies was
      discussed for both the single atomic anion and multiple atomic anion ionic
      liquids.

PMID- 16884213
TI  - Conjugated polymer/molten salt blend optimization.
AB  - Light-emitting electrochemical cells with low current threshold can be realized
      through mixing conjugated polymers and molten salts. Current drive capability is
      proportional to the overall interface perimeter of the planar, discotic molten
      salt domains inserted into the polymer matrix. Electric force microscopy
      indicates that this interface perimeter exhibits a specific dependence on the
      molten salt content in the active layer, with a well-defined maximum. We show
      that this maximum corresponds to an optimal current drive.

PMID- 16884212
TI  - Mixed atomistic and coarse-grained molecular dynamics: simulation of a membrane
      bound ion channel.
AB  - The recently developed multiscale coarse-graining (MS-CG) method (Izvekov, S.;
      Voth, G. A. J. Phys. Chem. B 2005, 109, 2469; J. Chem. Phys. 2005, 123, 134105)
      is used to build a mixed all-atom and coarse-grained (AA-CG) model of the
      gramicidin A (gA) ion channel embedded in a dimyristoylphosphatidylcholine (DMPC)
      lipid bilayer and water environment. In this model, the gA peptide was described
      in full atomistic detail, while the lipid and water molecules were described
      using coarse-grained representations. The atom-CG and CG-CG interactions in the
      mixed AA-CG model were determined using the MS-CG method. Molecular dynamics (MD)
      simulations were performed using the resulting AA-CG model. The results from
      simulations of the AA-CG model compare very favorably to those from all-atom MD
      simulations of the entire system. Since the MS-CG method employs a general and
      systematic approach to obtain effective interactions from the underlying all-atom
      models, the present approach to rigorously develop mixed AA-CG models has the
      potential to be extended to many other systems.

PMID- 16884214
TI  - Novel lasing action in dye-doped polymer films coated on large pseudotabular Ag
      islands.
AB  - An approximately 15 microm thick polymer film doped (approximately 5 mM) with a
      laser dye, when coated on large pseudotabular Ag islands and pumped by a
      nanosecond laser, generated a single sharp stimulated emission with a bandwidth
      down to 2.5 nm. We attribute this novel, low-threshold (approximately 1 mJ/cm(2))
      lasing action to the surface-enhanced fluorescence of the dyes very near the Ag
      islands. This highly surface-sensitive lasing concept was supported by the fact
      that the lasing action was almost completely eliminated by separating the Ag
      islands and the dye-doped polymer film with a molecularly thin (approximately 14
      A) spacer.

PMID- 16884215
TI  - Photoinduced surface dynamics of CO adsorbed on a platinum electrode.
AB  - The surface dynamics of adsorbed CO molecules formed by dissociative adsorption
      of HCHO at a polycrystalline Pt electrode/electrolyte solution interface was
      studied by picosecond time-resolved sum-frequency generation (TR-SFG)
      spectroscopy. A SFG peak at 2050-2060 cm(-1) was observed at the Pt electrode in
      HClO(4) solution containing HCHO at 0-300 mV (vs Ag/AgCl), indicating the
      formation of adsorbed CO at an atop site of the Pt surface as a result of
      dissociative adsorption of HCHO. The peak position varied with potential by
      approximately 33 cm(-1)/V, as previously found in an infrared reflection
      absorption spectroscopy (IRAS) study. Irradiation of an intense picosecond
      visible pulse (25 ps, 532 nm) caused an instant intensity decrease and broadening
      of the CO peak accompanied by the emergence of a new broad peak at approximately
      1980 cm(-1) within the time resolution of the system. These results suggest a
      decrease and increase in the populations of CO adsorbed on atop and bridge sites,
      respectively, upon visible pump pulse irradiation.

PMID- 16884216
TI  - Measurement of SO2 solubility in ionic liquids.
AB  - Measurements of the solubility of sulfur dioxide (SO(2)) in the ionic liquids 1-n
      hexyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([hmim][Tf(2)N]) and
      1-n-hexyl-3-methylpyridinium bis(trifluoromethylsulfonyl)imide ([hmpy][Tf(2)N])
      at temperatures from 25 to 60 degrees C and pressures up to 4 bar indicate that
      large amounts (up to 85 mol %) of SO(2) dissolve in ionic liquids by simple
      physical absorption.

PMID- 16884217
TI  - Open-system nonequilibrium steady state: statistical thermodynamics,
      fluctuations, and chemical oscillations.
AB  - Gibbsian equilibrium statistical thermodynamics is the theoretical foundation for
      isothermal, closed chemical, and biochemical reaction systems. This theory,
      however, is not applicable to most biochemical reactions in living cells, which
      exhibit a range of interesting phenomena such as free energy transduction,
      temporal and spatial complexity, and kinetic proofreading. In this article, a
      nonequilibrium statistical thermodynamic theory based on stochastic kinetics is
      introduced, mainly through a series of examples: single-molecule enzyme kinetics,
      nonlinear chemical oscillation, molecular motor, biochemical switch, and
      specificity amplification. The case studies illustrate an emerging theory for the
      isothermal nonequilibrium steady state of open systems.

PMID- 16884218
TI  - Comparative study of planar motion in monomeric and dimeric discotics.
AB  - Deuterium NMR spectra are reported in powder samples of discotic monomer and
      dimer as a function of temperature in their column Col(ho) phases. To simulate
      the observed powder patterns, a threefold jump model is used in the monomer,
      while in the related dimer the libration motion of the monomeric core is
      described using the infinitesimal jump method under a restricting potential due
      to the spacer. By comparing the diffusive rates for the two samples, it is
      concluded that the planar motion in the dimer is at least 30 times smaller than
      that of the monomer. This could lead to an enhancement of charge and energy
      transport in discotic dimer systems.

PMID- 16884219
TI  - Synthesis of TS-1 molecular sieves using a new Ti source.
AB  - The incorporation of Ti in the MFI structure using a cheap and easy to handle
      source, the hexafluorotitanic acid, was successfully achieved without the
      formation of contaminant phases. The TS-1 samples with 1%, 2%, and 2.5% Ti
      present a linear increase in the cell parameters. This indicates that the Ti
      present in the solid is incorporated into the framework, and this is confirmed by
      infrared analysis. The TS-1 particles present morphology that is typical of the
      MFI structure. The UV-vis diffuse reflectance results indicate the existence of
      tetra- and hexacoordinated framework Ti species. Independent of Ti content, all
      of the samples present similar activity for the oxidation of cyclohexene using
      hydrogen peroxide as an oxidant agent. Also, a high selectivity for the formation
      of the corresponding epoxide is observed.

PMID- 16884220
TI  - Polarization of charge-transfer bands and rectification in hexadecylquinolinium
      7,7,8-tricyanoquinodimethanide and its tetrafluoro analog.
AB  - A Langmuir-Blodgett (LB) multilayer film of the unimolecular rectifier hexadecyl
      gamma-quinolinium-7,7,8-tricyanoquinodimethanide (C(16)H(33)gammaQ-3CNQ) has two
      distinct polarized charge-transfer bands, one at lower film pressures (28 mN m(
      1)) with a peak at 530 nm, due to an intramolecular charge transfer or
      intervalence transfer (IVT); past the collapse point (32 to 35 mN m(-1)), this
      band disappears, and a new intermolecular charge-transfer band appears with peak
      at 570 nm. An LB multilayer film of the tetrafluoro analogue, hexadecyl-gamma
      quinolinium-2,3,5,6-tetrafluoro-7,7,8-tricyanoquinodimethanide (C(16)H(33)gammaQ
      3CNQF(4)) shows, for all film pressures, only one IVT band with a peak at 504 nm;
      when sandwiched between gold electrodes, (C(16)H(33)gammaQ-3CNQF(4) is also an LB
      monolayer electrical rectifier.

PMID- 16884221
TI  - Temperature scanning FTIR analysis of hydrogen bonding states of various
      saccharides in amorphous matrixes below and above their glass transition
      temperatures.
AB  - Temperature scanning Fourier transform infrared, TS-FTIR, spectroscopy of various
      amorphous sugar matrixes was conducted to investigate the relationship between
      the glass transition temperature, T(g), of an amorphous sugar matrix and the
      nature of the hydrogen bonds in the matrix. An amorphous sugar matrix was
      prepared by air-drying an aqueous solution of sugar, and the degree of formation
      of hydrogen bonds in the matrix was evaluated at different temperatures using the
      peak positions of the IR band corresponding to the O-H stretching vibration at
      around 3400 cm(-1). The T(g) value increased with increasing peak position of the
      O-H stretching vibration at T(g) and were correlated reasonably well with the
      magnitude of the peak shift by the temperature increase (from 25 degrees C) to
      the T(g) value. This demonstrates that the amorphous sugar matrix, in which the
      segments are fixed by fewer hydrogen bonds, has a higher thermal resistance. The
      glycosidic linkage largely contributes to the restriction of the segments,
      pyranose ring, rather than a hydrogen bond. As the degree of polymerization of
      pyranose rings increases, the degree of hydrogen bond formation needed to hold
      the matrix in a fixed position decreases. However, the magnitude of the
      restriction of pyranose rings by a glycosidic linkage changes depending on the
      type: the restrictions imposed by alpha-1,1 and -1,6 glycosidic linkages are the
      tightest and most flexible of all of the types of glycosidic linkages,
      respectively.

PMID- 16884222
TI  - Spectral and photophysical studies on cruciform oligothiophenes in solution and
      the solid state.
AB  - The photophysical and spectroscopic properties of a new class of oligothiophene
      derivatives, designated as cruciform oligomers, have been investigated in
      solution (room and low temperature) and in the solid state (as thin films in
      Zeonex matrixes). The study comprises absorption, emission, and triplet-triplet
      absorption spectra, together with quantitative measurements of quantum yields
      (fluorescence, intersystem crossing, internal conversion, and singlet oxygen
      formation) and lifetimes. The overall data allow the determination of the rate
      constants for all decay processes. From these, several conclusions are drawn.
      First, in solution, the main deactivation channels for the compounds are the
      radiationless processes: S(1) --> S(0) internal conversion and S(1) --> T(1)
      intersystem crossing. Second, in general, in the solid state, the fluorescence
      quantum yields decrease relative to solution. A comparison is made with the
      analogous linear alpha-oligothiophenes, revealing a lower fluorescence quantum
      efficiency and, in contrast to the normal oligothiophenes, that internal
      conversion is an important channel for the deactivation of the singlet excited
      state. Replacement of thiophene by 1,4-phenylene units in the longer-sized
      cruciform oligomer increases the fluorescence efficiency. The highly efficient
      generation of singlet oxygen through energy transfer from the triplet state
      (S(Delta) approximately 1) provides support for the measured intersystem crossing
      quantum yields and suggests that reaction with this may be an important pathway
      to consider for degradation of devices produced with these compounds.

PMID- 16884223
TI  - Ion concentration of external solution as a characteristic of micro- and nanogel
      ionic reservoirs.
AB  - Ion-sensitive hydrogel is regarded as an ionic reservoir, i.e., a system capable
      of changing the external pH or ionic strength by accumulating or releasing ions.
      The concept of a hydrogel ionic reservoir was demonstrated for hydrogel particles
      of three different size ranges: macrogel (1000-6000 microm), microgel
      (approximately 20-200 microm), and nanogel (approximately 0.2 microm). Ion
      sensitivity of poly(N-isopropylacrylamide-co-1-vinylimidazole) (PNIPA-VI)
      microgels with imidazolyl (ionizable) groups was confirmed by the pH dependence
      of their volume, while nanogels were characterized by dynamic light scattering.
      On the contrary, the volume of poly(N-isopropylacrylamide) (PNIPA) microgels
      without ionizable groups was pH independent in the whole range of pH from 10 to
      2. Four distinct regions of pH-behavior were observed for PNIPA-VI hydrogel micro
      and nanoparticles using potentiometric titration of their suspensions. Time
      resolved measurements of ion concentrations in the suspension of hydrogel
      particles revealed a substantial difference in kinetics of pH equilibration for
      (i) ion-sensitive hydrogels (PNIPA-VI) vs hydrogels without ionizable groups
      (PNIPA) and (ii) PNIPA-VI hydrogels of different sizes. On the basis of the
      experimental observations, a two-step mechanism affecting the kinetics of proton
      uptake into the hydrogel particles with ionizable groups was proposed: (1) fast
      binding of ions to the immediate surface of each particle and (2) a slower
      successive diffusion of bound sites into the next inner layer of polymer network.
      In accord with the mechanism proposed, a quasi-chemical kinetic model of pH
      relaxation to equilibrium was developed to fit the experimental data for the time
      course of proton uptake by macro-, micro-, and nanogels into two exponentials
      with the characteristic times of tau(1) and tau(2). We believe the same kinetic
      model will be pertinent to describe phenomenological and molecular mechanisms
      controlling proton transport in/out bacteria, cells, organelles, drug delivery
      vehicles, and other natural or artificial multifunctional ionic containers. The
      approach can be easily extended for the other ions (e.g., Na(+), K(+), and
      Ca(2+)).

PMID- 16884224
TI  - Crystalline and solution phases of N,N-dimethylethylenediamine complexed with
      lithium triflate and sodium triflate: intramolecular and intermolecular hydrogen
      bonding.
AB  - Infrared and Raman spectroscopy were used to study hydrogen-bonding interactions
      and the cation coordination effect in solutions of N,N-dimethylethylenediamine
      (DMEDA) with lithium triflate (LiTf) and sodium triflate (NaTf). A comparison of
      pure DMEDA with DMEDA dissolved in carbon tetrachloride enabled the separation of
      the relative contributions of intermolecular and intramolecular hydrogen-bonding
      interactions to the N-H stretching frequencies. The addition of LiTf and NaTf to
      DMEDA shifts the N-H stretching frequencies through two competing effects: the
      cation coordination effect lowers the frequencies, while the disruption of the
      hydrogen-bonding interactions increases the frequencies. These two effects were
      distinguished in a study of the concentration dependence of both salts dissolved
      in DMEDA; the differentiation was based on the difference in the spectral
      sensitivities of the symmetric and the antisymmetric stretch in both the Raman
      and infrared spectra. During this study, DMEDA-LiTf and DMEDA-NaTf crystals were
      discovered, and their structures were solved by X-ray diffraction techniques. The
      analysis of the vibrational spectra of these crystals was greatly enhanced by
      unambiguous knowledge of the structural details of cation-molecule and anion
      cation interactions. These structure-spectra correlations were used to complement
      analogous spectroscopic studies in the solution phases. Analysis of spectral
      regions in both crystalline and solution phases particularly sensitive to the
      nature and strength of cation-molecule interactions clearly established that the
      interaction of the lithium ion with the nitrogen atoms of DMEDA was stronger than
      the sodium ion-DMEDA interaction, as expected from charge density arguments.

PMID- 16884225
TI  - Molecular structure of a D-homoandrostanyl steroid derivative: single crystal and
      powder diffraction analyses.
AB  - The knowledge of the structure of a molecular crystal is frequently a
      prerequisite for the understanding of its solid state properties. Even though
      single-crystal diffractometry is the method of choice when it comes to crystal
      structure determination, methods using powder diffraction data become more and
      more competitive. There has been much recent interest in the development of a new
      generation of "direct-space" approaches that are particularly suited for
      molecular crystals. The crystallographic structure of a steroid derivative
      molecule (17,17-di-n-propyl-17a-aza-D-homo-5alpha-androstan-3beta-ol) was
      obtained in two independent ways: from a single crystal by laboratory X-rays and
      from a polycrystalline powder by high-resolution synchrotron powder diffraction.
      The molecule crystallizes in the orthorhombic space group P2(1)2(1)2(1) (a =
      6.5346, b = 17.6006 and c = 19.6978 A). Hydrogen bonds form infinite chains of
      molecules parallel to the c axis.

PMID- 16884226
TI  - Relative brookite and anatase content in sol-gel-synthesized titanium dioxide
      nanoparticles.
AB  - Sol-gel synthesis of titania typically produces a mixture of brookite and
      anatase. Rietveld refinements were used to systematically track the brookite
      content and particle size as functions of synthetic variables. Results
      demonstrate that brookite content and anatase particle size decrease with
      decreasing Ti/H(2)O ratios. In syntheses at pH 3, the addition of HCl resulted in
      increased amorphous content compared to samples synthesized using HNO(3). Similar
      amorphous contents were observed for particles prepared at pH 6-9. Hydrothermal
      aging for 4 h at 200 degrees C of sol-gel products containing substantial
      amorphous titania resulted in higher brookite content than did hydrothermal aging
      of sol-gel products containing little to no amorphous titania. Finally, dialysis
      prior to hydrothermal aging appeared to inhibit phase transformation from
      brookite to anatase in aged materials. Results presented demonstrate that
      considerable control over the relative anatase and brookite contents can be
      achieved through control of synthetic variables.

PMID- 16884227
TI  - Nonlinear absorption and nonlinear refraction of self-assembled porphyrins.
AB  - Nonlinear refraction and nonlinear absorption of self-assembled porphyrins in the
      nanosecond and picosecond regimes were studied at 532 nm by the Z-scan technique.
      First, a marked difference in nonlinear refraction was observed between self
      assembled zinc porphyrins and free base porphyrins; however, the effects of self
      assembly and metallization on nonlinear absorption are small. Second, an
      enhancement of nonlinear absorption was observed for the monomeric components of
      self-assembled structures by adding pyridine, while their nonlinear refractions
      remained almost unchanged as pyridine was added. It is expected that the
      metallization and addition of ligand can provide more convenient routes to alter
      the optical nonlinearities of porphyrins than the modifications of molecular
      structures of traditional covalent-bond organic materials.

PMID- 16884228
TI  - Thickness-dependent photocatalytic performance of ZnO nanoplatelets.
AB  - In this paper, we report the large-scale synthesis of ZnO nanoplatelets as thin
      as 10 nm. The nanoplatelets show higher efficiency in photodegrading organic dyes
      than ZnO nanorods do, and for the nanoplatelets, the thinner they are, the higher
      the performance. The photocatalytic decomposition of organic dyes (eosin B) by
      ZnO nanoplatelets compares favorably to the performances of ZnS porous
      nanoparticles and commercial Degussa P25 titania particles. This finding may have
      significant implications in the environment remediation and the fabrication of
      functional nanodevices.

PMID- 16884229
TI  - Facile synthesis and catalytic property of porous tin dioxide nanostructures.
AB  - Porous tin dioxide (SnO(2)) nanostructures consisting of nanoplates are prepared
      through thermal decomposition of the mixed solution composed of dibutyltin
      dilaurate and acetic acid. The aggregations of the nanoplates give rise to large
      macropores with the size of about 100-300 nm. These nanoplates have a wormhole
      like porous structure with the size of about 4 nm and possess high surface area.
      X-ray powder diffraction, transmission electron microscopy, scanning electron
      microscopy, infrared spectroscopy, and nitrogen sorption have been employed to
      characterize the obtained porous structures. It is found that the obtained
      nanostructures exhibit excellent catalytic activity toward methanol
      decomposition. Such porous structures with high surface area have promising
      industrial applications as catalysts.

PMID- 16884230
TI  - Quantitative SAXS analysis of the P123/water/ethanol ternary phase diagram.
AB  - The ternary phase diagram of the amphiphilic triblock copolymer PEO-PPO-PEO
      ((EO)(20)(PO)(70)(EO)(20) commercialized under the generic name P123), water, and
      ethanol has been investigated at constant temperature (T = 23 degrees C) by small
      angle X-ray scattering (SAXS). The microstructure resulting from the self
      assembly of the PEO-PPO-PEO block copolymer varies from micelles in solution to
      various types of liquid crystalline phases such as cubic, 3D hexagonal close
      packed spheres (HCPS), 2D hexagonal, and lamellar when the concentration of the
      polymer is increased. In the isotropic liquid phase, the micellar structural
      parameters are obtained as a function of the water-ethanol ratio and block
      copolymer concentration by fitting the scattering data to a model involving core
      shell form factor and a hard sphere structure factor of interaction. The micellar
      core, the aggregation number, and the hard sphere interaction radius decrease
      when increasing the ethanol/water ratio in the mixed solvent. We show that the
      fraction of ethanol present in the core is responsible for the swelling of the
      PPO blocks. In the different liquid crystalline phases, structural parameters
      such as lattice spacing, interfacial area of PEO block, and aggregation number
      are also evaluated. In addition to classical phases such as lamellar, 2D
      hexagonal, and liquid isotropic phases, we have observed a two-phase region in
      which cubic Fm3m and P6(3)mmc (hexagonally close packing of spheres (HCPS))
      phases coexist. This appears at 30% (w/w) of P123 in pure water and with 5% (w/w)
      of ethanol. At 10% (w/w) ethanol, only the HCPS phase remains present.

PMID- 16884231
TI  - mu-GISAXS experiment and simulation of a highly ordered model monolayer of PMMA
      beads.
AB  - Uniform sized PMMA-beads were deposited as a monolayer on silicon substrates
      using dip-coating techniques. High-resolution grazing incidence X-ray small angle
      scattering experiments were performed using a micrometer sized beam (mu-GISAXS)
      to determine the structure of a highly ordered monolayer with two-dimensional
      hexagonal arrays. A clear and strong interference pattern coming from the
      reflection and refraction effects of particles on flat surfaces with small
      uncorrelated roughnesses is shown. The quantitative analysis and simulations of
      the X-ray scattering pattern have been performed, and a detailed explanation of
      the analysis is reported. The results were directly compared and verified with
      atomic force microscopy (AFM) measurements and their resulting FFT spectra.

PMID- 16884232
TI  - Nature, structure and strength of the acidic sites of amorphous silica alumina:
      an IR and NMR study.
AB  - IR spectroscopy of probe molecules (pyridine, 2,6-dimethylpyridine, and CO) as
      well as high-resolution solid state NMR and especially double-resonance
      experiments give a new insight into the acidic sites of amorphous silica alumina
      (ASA). ASA samples are heterogeneous compounds that contain a silica alumina
      mixed phase as well as aluminum clusters and pure silica zones. The distribution
      of various forms depends both on the preparation method and on the Si/Al ratio.
      Formation of mixed phase leads to the creation of acidic hydroxyl groups of
      various strength, up to that present in dealuminated HY zeolite. Detailed
      spectroscopic analyses show that these acidic OH groups correspond to the silanol
      groups located in close vicinity to an Al atom in tetrahedral environment. The
      strength of the acidity of the OH species of ASA could be modified both by the
      location of the vicinal Al atom on the surface or in the bulk and by the number
      of aluminum atoms in the vicinity of silanol group. Cogelification of high silica
      containing ASA appears as the best mean to prepare homogeneous amorphous
      aluminosilicate, which exhibits the strongest Bronsted acidity.

PMID- 16884233
TI  - Mechanism of ZnO nanotube growth by hydrothermal methods on ZnO film-coated Si
      substrates.
AB  - ZnO nanorods (NRs) and nanotubes (NTs) have been synthesized by a hydrothermal
      method on Si substrates that had been precoated (by pulsed laser deposition
      (PLD)) with a thin ZnO film. High-resolution transmission electron microscopy and
      selected area electron diffraction analysis confirm that the NTs are ZnO single
      crystals and that their growth direction is along [0001] (the c-axis). Scanning
      electron microscopy points to the early-time formation of two classes of NRs on
      the PLD ZnO coating, one of which is longer and displays higher length/diameter
      aspect ratios than the other. The morphologies of NRs belonging to the first of
      these classes were seen to evolve with time, progressively tapering, and
      producing volcano-like surface structures that develop into NTs. In contrast, NRs
      belonging to the other (shorter) class retain their hexagonal cross-section and
      have flat tops. To explain these emergent structures and, in particular, the
      selective growth of ZnO NTs, we have undertaken a systematic investigation of the
      effects of different substrates (e.g., borosilicate glass, Pt-coated glass, and
      both bare and PLD ZnO-coated Si wafers) and of the reactive solution on the
      growth properties of ZnO NRs, NTs, and the ZnO nanopowders that precipitate from
      the reactive mixture. The experimental findings suggest the following ZnO NT
      growth mechanism. The PLD ZnO film consists of many nanocrystallites, with a
      preferred c-axis alignment. These serve to nucleate the hydrothermal growth of (c
      axis aligned) NRs. The NRs are deduced to be Zn-polar, but can be either Zn-atom
      or O-atom terminated. It is proposed that the different surface terminations
      influence (by electrostatic interactions) the cation (Zn(2+) and ZnOH(+)) to
      anion (OH(-)) concentration ratio in the double layer at the growing polar
      surface. Zn-atom termination causes a reduction in the local Zn(2+)/OH(-) (and
      ZnOH(+)/OH(-)) ratios (i.e., the extent of solution supersaturation) relative to
      those in the bulk solution, thereby encouraging tapered NR growth and, as the
      zinc concentration falls further, the emergence of volcano-like structures on the
      polar surface, which seed the subsequent growth of ZnO NTs.

PMID- 16884234
TI  - Deuterium NMR of the TGBA* phase in chiral liquid crystals.
AB  - A deuterium NMR (DNMR) study of the TGBA* (twist grain boundary smectic A*) phase
      in an NMR magnetic field of 9.4 T for the chiral compound 4-[4'-(1-methyl
      heptyloxy)] biphenyl 4-(10-undecenyloxy) benzoate (11EB1M7) is reported. The
      deuterium two-dimensional (2D) exchange spectra were observed for the first time
      in this phase. The present study allows us to learn how the helicoidal structures
      arrange in an external magnetic field. To derive quantitative kinetic parameters
      of this novel phase, both 1D and 2D experimental spectra were simulated by means
      of a jump diffusion model. By comparing the experimental and simulated spectra,
      an accurate determination of the dynamic parameters in the TGBA* phase was
      obtained. Furthermore, the twist angle between two neighboring smectic A blocks
      is found as 26 +/- 10 degrees, which is consistent with the X-ray results for
      similar chiral liquid crystals. The diffusion constant (D(parallel)) is estimated
      to be 3.2 x 10(-12) m(2)/s at 379.5 K.

PMID- 16884235
TI  - A distribution kinetics approach for crystallization of polymer blends.
AB  - The cluster distribution approach is extended to investigate the crystallization
      kinetics of miscible polymer blends. Mixture effects of polymer-polymer
      interactions are incorporated into the diffusion coefficient. The melting
      temperature, activation energy of diffusion, and phase transition enthalpy also
      depend on the blending fraction and lead to characteristic kinetic behavior of
      crystallization. The influence of different blending fractions is presented
      through the time dependence of polymer concentration, number and size of
      crystals, and crystallinity (in Avrami plots). Computational results indicate how
      overall crystallization kinetics can be expressed approximately by the Avrami
      equation. The nucleation rate decreases as the blending fraction of the second
      polymer component increases. The investigation suggests that blending influences
      crystal growth rate mainly through the deposition-rate driving force and growth
      rate coefficient. The model is further validated by simulating the experimental
      data for the crystallization of a blend of poly(vinylidenefluoride)[PVDF] and
      poly(vinyl acetate)[PVAc] at various blending fractions.

PMID- 16884237
TI  - Fabrication and characterization of mesoporous Co3O4 core/mesoporous silica shell
      nanocomposites.
AB  - A mesoporous Co(3)O(4) core/mesoporous silica shell composite with a variable
      shell thickness of 10-35 nm was fabricated by depositing silica on Co(3)O(4)
      superlatticed particles. The Brunauer-Emmett-Teller (BET) surface area of the
      composite with a shell thickness of ca. 2.0 nm was 238.6 m(2)/g, which varied
      with the shell thickness, and the most frequent pore size of the shell was ca.
      2.0 nm. After the shell was eroded with hydrofluoric acid, mesoporous Co(3)O(4)
      particles with a pore size of ca. 8.7 nm could be obtained, whose BET surface
      area was 86.4 m(2)/g. It is proposed that in the formation of the composite the
      electropositive cetyltrimethylammonium bromide (CTAB) micelles were first
      adsorbed on the electronegative Co(3)O(4) particle surface, which directed the
      formation of the mesoporous silica on the Co(3)O(4) particle surface.
      Electrochemical measurements showed that the core/shell composites exhibited a
      higher discharge capacity compared with that of the bare Co(3)O(4) particles.

PMID- 16884236
TI  - Dynamic and 2D NMR studies on hydrogen-bonding aggregates of cholesterol in low
      polarity organic solvents.
AB  - Self-diffusion coefficients (D) are measured for normal (nondeuterated) and
      deuterated cholesterol-d(6) (C26 and C27 methyl groups deuterated) in 1-octanol,
      chloroform, and cyclohexane at concentrations of 1-700 mM by varying the impurity
      water concentration (>2 mM) and temperature (30-50 degrees C). The pulsed field
      gradient spin-echo (PGSE) (1)H and (2)H NMR were used, respectively, at 600 and
      92 MHz. At 30 degrees C, the hydrodynamic radius (R) obtained at 20 mM from the D
      value and solvent viscosity is 5.09, 7.07, and 6.17 A, respectively, in 1
      octanol, chloroform, and cyclohexane when the impurity water is negligible. The R
      value in 1-octanol is the smallest and comparable with the average length of the
      molecular axes for the cholesterol molecule. In 1-octanol, R is invariant against
      the concentration variation, whereas in chloroform, R is larger and increases
      almost linearly with cholesterol concentration. At the highest concentration, 700
      mM, the R in chloroform is 13.5 and 16.7 A, respectively, when the impurity water
      is at negligible and saturated concentrations. The R value larger than that in
      hydrogen-bonding 1-octanol indicates that cholesterol forms an aggregate through
      hydrogen bonding. The aggregate structure is confirmed by comparing NOESY spectra
      in chloroform and 1-octanol. The NOESY analysis reveals the presence of one extra
      cross peak (C4-C19) in chloroform compared to 1-octanol. Because the carbon atoms
      related to the cross peak are close to the hydroxyl group (C3-OH), cholesterol
      molecules are considered to be not piled but are found to be OH-centered in the
      aggregate. This is supported also by larger rotational hydrodynamic radii
      measured on cholesterol deuterated at positions C2, C3, C4, and C6. This shows
      that the aggregate formation is driven by the hydrogen-bonding between
      cholesterol molecules.

PMID- 16884238
TI  - Surfactant-assisted synthesis of alpha-Fe2O3 nanotubes and nanorods with shape
      dependent magnetic properties.
AB  - Alpha-Fe(2)O(3) nanorods and nanotubes have been synthesized and characterized by
      high-resolution transmission electron microscopy and X-ray diffraction. By means
      of different surfactant assistance, the high-quality one-dimensional products
      were obtained, respectively, with aqueous butanol solution as the solvent and
      carbamide as the base, giving rise to single-crystalline products at 150 degrees
      C. The formation mechanism has been presented. Significantly, the magnetic
      investigations show that the magnetic properties are strongly shape-dependent;
      i.e., the nanorods have a Morin transition at 166 K from canted antiferromagnetic
      state to antiferromagnetic state, while the nanotubes exhibit a three-dimensional
      magnetic ordering above 300 K that has been attributed to the presence of small
      particles in a few regions of the tubes.

PMID- 16884239
TI  - Molecular hydrogels from bile acid analogues with neutral side chains: network
      architectures and viscoelastic properties. Junction zones, spherulites, and
      crystallites: phenomenological aspects of the gel metastability.
AB  - Structural and rheological properties of hydrogels made up of neutral bile acid
      derivatives are studied. Complementary scattering, diffraction, and microscopy
      techniques provide a precise structural description of the network architecture
      and its variation as a function of concentration, aging time, composition of the
      solvent, and type of gelator. Two derivatives (TH and PH) are considered as
      presenting favorable scattering features to approach the issue of the competition
      between gelation versus crystallization. PH and TH fibers are semirigid cylinders
      with monodisperse cross-sections (R(0) = 92 and 80 A, respectively) involving 25
      or 12 molecules per cross-sectional repeating unit along the fiber axis. Bundles
      are cross-links in the networks, and a scattering protocol is developed to
      determine the nodal and fibrillar fractions in the networks. The effects of
      alcoholic mixtures, dimethylsulfoxide, and temperature on the network properties
      are analyzed in terms of the bending modulus of the fibers, the degree of
      nonaffine character of the regime of deformation, and the dispersion degree of
      the nodal heterogeneities. It is shown that fibers are semirigid and the scaling
      laws of the elasticity of the gels with the concentration (exponent (5)/(2)) also
      support the theoretical context. Head-to-tail molecular arrangements are shown to
      be similar in the solid and gel phases. Birefringent textures show that
      spherulitic microdomains coexist in the network texture and are the seeds for a
      slow crystallization process. The whole pattern might be more general for
      numerous other self-assembled fibrillar networks found in molecular gels.

PMID- 16884241
TI  - Unraveling internal structures of highly luminescent PbSe nanocrystallites using
      variable-energy synchrotron radiation photoelectron spectroscopy.
AB  - The internal structure of PbSe nanocrystals was deduced using synchrotron X-ray
      photoemission spectroscopy for three different sizes of nanocrystals. The
      photoemission data revealed the layered structure of PbSe nanocrystals with the
      crystalline PbSe core surrounded by a nonstoichiometric Pb(1-x)Se shell, finally
      passivated by a capping agent in the outermost layer. A detailed analysis of the
      experimental data yielded quantitative information on the thickness of three
      different layers, which is unavailable through any other technique; moreover, the
      overall sizes of the nanocrystals probed by transmission electron microscopy were
      in agreement with the corresponding quantity obtained in the present experiment.
      The present results provide a plausible explanation for the strong variation in
      the photoluminescence intensity with size observed for these nanocrystals.

PMID- 16884240
TI  - Fabrication of zinc ferrite nanocrystals by sonochemical emulsification and
      evaporation: observation of magnetization and its relaxation at low temperature.
AB  - A new ultrasound assisted emulsion (consisting of rapeseed oil and aqueous
      solution of Zn(2+) and Fe(2+) acetates) and evaporation protocol has been
      developed for the synthesis of zinc ferrite (ZnFe(2)O(4)) nanoparticles with
      narrow size distribution. The as-synthesized sample consisted of crystalline zinc
      ferrite particles with an average diameter of approximately 4 nm, whereas the
      average size of the heat-treated ferrite particles increases to approximately 12
      nm. To remove the small amount of oil present on the surface of the as
      synthesized ferrite sample, heat treatment was carried out at 350 degrees C for 3
      h. The as-synthesized and heat-treated ferrites were characterized by X-ray
      diffraction (XRD), infrared spectroscopy (IR), TGA/DTA, transmission electron
      microscopy (TEM), and energy dispersion X-ray spectroscopy (EDS) techniques.
      Magnetic measurements show that the nanocrystalline ZnFe(2)O(4), prepared through
      this technique, is either at par with those obtained in other cases or even more
      improved. Both the as-synthesized and heat-treated samples reveal relaxation of
      magnetization. Our study also shows that one can tailor the magnetization and
      relaxation pattern by suitably controlling the particle size of the
      nanocrystalline ZnFe(2)O(4). The key features of this method are avoiding (a) the
      cumbersome conditions that exist in the conventional methods, (b) the usage of
      necessary additive components (stabilizers or surfactants, precipitants), and (c)
      calcination requirements. In addition, rapeseed oil has replaced organic nonpolar
      solvents used in earlier studies. As a whole, this simple straightforward
      sonochemical approach results in a better pure phase system of nanoferrite with
      improved magnetic properties.

PMID- 16884242
TI  - Influence of single versus double hydrogen-bonding motif on the crystallization
      and morphology of self-assembling carbamates with alkyl side chains: model system
      for polyurethanes.
AB  - The difference in the morphology and crystallization aspects of hydrogen-bond
      mediated self-assembling systems with single and double hydrogen-bonding motifs
      is studied here with carbamates as an example. These carbamates have alkyl side
      chains of various lengths, from C(4) to C(18). The biscarbamates with double
      hydrogen-bonding sites and symmetric substitution of alkyl segments show a
      significantly different morphological behavior as compared to the N-octadecyl
      carbamate alkyl esters (ref 5, referred to as simple carbamates henceforth) with
      a single hydrogen-bond motif and asymmetric substitution of alkyl side chains. In
      contrast to the simple carbamates in which no significant difference was found in
      the spherulite size from C(4) to C(12), with the biscarbamates we find that the
      spherulitic size, rate of growth of spherulites, and rate of crystallization show
      a maximum with an alkyl chain length of C(8). This is rationalized in terms of
      the relative contributions of the hydrogen-bond and van der Waals interaction
      energies. Oriented X-ray diffraction patterns from the fibrils of the spherulites
      lead to a model for the growth patterns of the hydrogen-bond planes and the
      molecular orientation in the spherulites.

PMID- 16884243
TI  - Adsorption of DNA into mesoporous silica.
AB  - In these experiments, double-stranded, linear DNA sequences were adsorbed into
      the pores of spherically shaped acid-prepared mesoporous silica (APMS). The
      lengths of the sequences were either 760 base pairs or 2000 base pairs. DNA
      adsorption into the interior of the mesoporous material was confirmed using
      confocal microscopy of sequences containing fluorescently labeled DNA molecules.
      Additional characterization with N(2) physisorption and powder X-ray diffraction
      supported this finding. The extent of adsorption was measured at various
      concentrations using UV-visible spectrophotometry to establish adsorption
      isotherms. APMS alone adsorbed a negligible amount of DNA; however, exchanging
      divalent cations such as Mg(2+) and Ca(2+) into the pores of APMS prior to DNA
      uptake was found to cause a significant amount of DNA to be adsorbed. Using Na(+)
      caused a lower amount of DNA to be adsorbed. DNA adsorption was also dependent on
      the pore diameter of APMS. Adsorption increased upon expansion of the pore size
      of the metal ion-exchanged material from 34 to 54 A; however, no additional
      uptake was measured by further increasing the pore size to 100 A. The amount of
      DNA adsorbed could also be significantly increased by using
      (aminopropyl)triethoxysilane to covalently link ammonium ions to the surface.
      Postsynthetic modification of the silica surface with aminopropyl groups
      increased the maximum DNA adsorption to 15.7 microg/mg silica, for materials with
      pore diameters of 100 A, which is 2 to 3 times more adsorbed DNA than for metal
      ion-exchanged material. This indicated that DNA binds more strongly in the
      presence of the ammonium group compared to the metal counterions. Finally,
      calculation and comparison of Freundlich and Langmuir constants for these
      adsorption processes indicate that intermolecular interactions between the DNA
      molecules within the pores are significant when the effective pore diameter is
      small, including materials with larger pores that were modified with
      organosilane.

PMID- 16884244
TI  - Silica nanoarchitectures with tailored pores based on the hybrid three- and four
      membered rings.
AB  - Inspired by the recent developments in the controlled synthesis of porous
      materials, we present herein the structural prediction of silica
      nanoarchitectures by using the three- (3MRs) and four-membered rings (4MRs),
      which are more frequently found in the nanometer-sized particles than in the bulk
      form, as building blocks. The proposed models include the active molecular rings,
      thin nanowires, hollow nanotubes, discrete fullerene-like cages, and porous
      zeolite-like three-dimensional networks. Their geometrical and electronic
      structures and properties were studied by performing density functional
      calculations. These silica nanostructures were proved, using molecular dynamics
      simulations, to possess intrinsic structural stabilities with highly symmetrical
      geometries and regular nanochannels. These atomically well-defined clusters,
      (SiO)(n), are chemically more reactive than those proposed earlier and are
      energetically more favorable for n > 20 in high-level density functional
      calculations over the corresponding two-membered ring (2MR) chains and rings as
      well as the pure 3MR networks. The nanoparticles and nanodevices based on them
      are expected to have potential technological applications that mainly make use of
      their characteristic geometrical structures (nanosized pores) and novel
      electronic properties.

PMID- 16884245
TI  - Optoelectronic switches based on wide band gap semiconductors.
AB  - Switching of photocurrent direction in semiconducting systems upon changes of the
      electrode potential or incident light wavelength was realized by a series of
      photoelectrodes covered with titania modified with pentacyanoferrate complexes,
      [Fe(CN)(5)L](n)(-) (L = NH(3), thiodiethanol, thiodipropanol). These materials
      were characterized by optical spectroscopy and electrochemistry. The structure of
      the surface complexes was modeled using simple quantum-chemical models. The
      electrodes described in this paper enable control of the photocurrent direction
      by two stimuli: Changing the wavelength or the photoelectrode potential easily
      switches the direction of photocurrent. The materials are different from those of
      similar characteristics studied by other authors: They are not composites
      comprising of two types of semiconductors but rather engineered uniform
      materials. The photocurrent switching phenomenon is an intrinsic feature
      resulting from a specific electronic structure of the surface-modified
      semiconductor.

PMID- 16884246
TI  - Effect of rare-earth component of the RE/Ni catalyst on the formation and
      nanostructure of single-walled carbon nanotubes.
AB  - A systematic experimental study has been carried out on the efficiency of
      bimetallic catalysts based on Ni and the rare-earth elements Y, La, Ce, Nd, Gd,
      Tb, Dy, Ho, Er, and Lu (group A) and Eu, Sm, Yb, and Tm (group B) in the
      synthesis of single-walled carbon nanotubes (SWNTs). The two groups give quite
      different results when analyzed by a combination of SEM/TEM and Raman and UV-NIR
      spectroscopies. The elements in group A have an obvious catalytic effect and
      increase the yield of SWNTs dramatically, whereas those in group B are not
      efficient catalysts. The diameter distribution of the synthesized SWNTs was also
      affected by the rare-earth element used. For group A metals, there is a tendency
      that the fraction of small-diameter tubes decreases with decreasing ionic radius
      of the rare-earth element used. EDX and X-ray analyses indicate that group A
      metals deposit on the cathode deposits and form rare-earth carbides, whereas no
      group B metals are found in cathode deposits, except for a small amount of Tm
      present in the form of thulium carbide. Further analysis indicates that there is
      a very strong correlation between the ability to form rare-earth carbides and the
      catalytic efficiency for the formation of SWNTs.

PMID- 16884247
TI  - Functionalization of carbon nanotubes with Vaska's complex: a theoretical
      approach.
AB  - The functionalization of single-walled carbon nanotubes (CNTs) with Vaska's
      complex trans-Ir(CO)Br(PPh(3))(2) has been investigated by means of hybrid
      quantum mechanics/molecular mechanics (QM/MM) calculations. The formation of a
      stable adduct has been experimentally evidenced by Wong et al. (Nano Lett. 2002,
      2, 49), but microscopical details on the metal-nanotube interaction are still
      unclear. Our calculations show a low propensity to eta(2) coordination of Vaska's
      complex with the perfect hexagonal network of CNTs. Rather, a stronger
      interaction takes place when the transition metal center coordinates to carbon
      atoms belonging to pentagonal rings, as in topological defects or end-caps.

PMID- 16884248
TI  - Transient solidlike behavior near the cylinder/disorder transition in block
      copolymer solutions.
AB  - A nearly symmetric polystyrene-block-polyisoprene diblock copolymer dissolved at
      a concentration of 40% in styrene-selective solvents exhibited a cylinder-to
      disorder transition upon heating. The solvents used were diethyl phthalate (DEP)
      and 75:25 and 50:50 mixtures of DEP with di-n-butyl phthalate (DBP). In DEP, the
      most styrene-selective of the three solvents, rheological measurements indicated
      a distinct plateau in the temperature-dependent elastic modulus across the 8
      degrees C interval above the order-disorder transition temperature, T(ODT) = 116
      degrees C. Previous small-angle neutron scattering measurements in this regime
      indicated the equilibrium phase to be a liquidlike solution of approximately
      spherical micelles. An isothermal frequency sweep in this regime indicated a very
      long relaxation time. Annealing eventually led to the recovery of liquidlike
      rheological response, over a time scale of hours. Qualitatively similar phenomena
      were also observed in 75:25 DEP/DBP and 50:50 DEP/DBP solutions, except the fact
      that the temperature window of the transient response is narrow and the time
      scale for the recovery diminishes significantly. Neither small-angle X-ray
      scattering nor static birefringence gave any clear signature of the transient
      structure. The structure that leads to the transient rheological response is
      attributed to micellar congestion due to the slow relaxation of anisotropic
      micelles into an equilibrium distribution of micelles. Possible origins of the
      remarkable solvent selectivity dependence are also discussed.

PMID- 16884249
TI  - Ionic motion in crystalline cryolite.
AB  - The character of the ion dynamics in crystalline cryolite, Na(3)AlF(6), a model
      double perovskite-structured mineral, has been examined in computer simulations
      using a polarizable ionic potential obtained by force-fitting to ab initio
      electronic structure calculations. NMR studies, and conductivity measurements,
      have indicated a high degree of mobility, in both Na(+) ion diffusion and
      reorientation of the AlF(6) octahedral units. The simulations reproduce the low
      temperature (tilted) crystal structure and the existence of a transition to a
      cubic structure at elevated temperatures, in agreement with diffraction
      measurements, though the calculated transition temperature is too low. The
      reorientational dynamics of the AlF(6) octahedra is shown to consist of a hopping
      motion between the various tilted positions of the low-temperature form, even
      above the transition temperature. The rate of reorientation estimated by
      extrapolation to the temperature regime of the NMR measurements is consistent
      with the experimental data. In addition, we report a novel cooperative "tilt
      swapping" motion of the differently tilted sublattices, just below the transition
      temperature. The perfect crystals show no Na(+) diffusion, in apparent
      disagreement with observation. We argue, following previous analyses of the
      cryolite phase diagram, that the diffusion observed in the experimental studies
      is a consequence of defects that are intrinsic to the thermodynamically stable
      form of cryolite. By introducing defects into the simulation cell, we obtain
      diffusion rates that are consistent with the NMR and conductivity measurements.
      Finally, we demonstrate a link between diffusion of the Na(+) ions and the
      reorientation of AlF(6) units, though the correlation between the two is not very
      strong.

PMID- 16884250
TI  - Photoluminescent layered Y(III) and Tb(III) silicates doped with Ce(III).
AB  - The synthesis and structural characterization of new layered rare-earth silicates
      K(3)[M(1-a)Ce(a)Si(3)O(8)(OH)(2)], M = Y(3+), Tb(3+), a << 1 (AV-22 materials),
      have been reported. These materials combine the properties of layered silicates,
      such as intercalation chemistry, and photoluminescence and may find applications
      in new types of sensor devices. For mixed Tb/Ce-AV-22, evidence has been found
      for the energy transfer from the large Ce(3+) 4f( 1) --> 5d(1) broad band to the
      sharp Tb(3+) 4f (8) lines. This energy transfer allows the fine-tuning of the
      color emission in the blue-green region of the chromaticity diagram. Upon Ce(3+)
      excitation (342 nm), the radiance of Tb/Ce-AV-22 is approximately 2 times higher
      than that measured under direct Tb(3+) excitation, which reinforces the existence
      of effective room-temperature Ce(3+)-to-Tb(3+) energy transfer.

PMID- 16884251
TI  - Resident neuroelectrochemical interfacing using carbon nanofiber arrays.
AB  - Carbon nanofiber electrode architectures are used to provide for long-term,
      neuroelectroanalytical measurements of the dynamic processes of intercellular
      communication between excitable cells. Individually addressed, vertically aligned
      carbon nanofibers are incorporated into multielement electrode arrays upon which
      excitable cell matrixes of both neuronal-like derived cell lines (rat
      pheochromocytoma, PC-12) and primary cells (dissociated cells from embryonic rat
      hippocampus) are cultured over extended periods (days to weeks). Electrode arrays
      are characterized with respect to their response to easily oxidized
      neurotransmitters, including dopamine, norepinephrine, and 5-hydroxytyramide.
      Electroanalysis at discrete electrodes following long-term cell culture
      demonstrates that this platform remains responsive for the detection of easily
      oxidized species generated by the cultured cells. Preliminary data also suggests
      that quantal release of easily oxidized transmitters can be observed at nanofiber
      electrodes following direct culture and differentiation on the arrays for periods
      of at least 16 days.

PMID- 16884252
TI  - Highly ordered polymer films of amphiphilic, regioregular polythiophene
      derivatives.
AB  - The fabrication and characterization of highly ordered thin films made from
      amphiphilic, regioregular polythiophene derivatives are described. Films of
      poly(3-(11-(2-tetrahydropyranyloxy)undecyl)thiophene (PTHPUDT) were prepared by
      the Langmuir-Blodgett technique. The amphiphilic nature of the polymer affords
      layer-by-layer deposition and the formation of multilayer films of head-to-head
      and tail-to-tail Y-type structure. X-ray diffraction studies indicate bilayer
      separations of approximately 30 A. Anisotropic optical absorption in the plane of
      the film indicates that the thiophene backbones are preferentially oriented along
      the dipping direction. Further, polarized light microscopy studies indicate that
      these films are highly birefringent and that the optical retardation is uniform
      over the entire film. Ellipsometry studies confirm the sizable magnitude of the
      birefringence. Optical second-harmonic generation studies of multilayer films
      provide information regarding both the thiophene orientation within the film and
      the anisotropic distribution of chromophores in the surface plane. Taken
      together, these data offer strong evidence of highly ordered films in which the
      hydrophobic polythiophene chains lie parallel to the substrate surface with their
      alkyl chains oriented normal to the surface, as dictated by the hydrophilic
      nature of the alkyl chain's terminal tetrahydropyran functional group. As such,
      these films offer the potential for elucidating the connection between polymer
      morphology and physical property in materials that are otherwise subject to a
      sufficiently complex distribution of morphologies that such a correspondence is
      precluded.

PMID- 16884253
TI  - Mechanistic study of the electrochemical oxygen reduction reaction on Pt(111)
      using density functional theory.
AB  - Density functional theory (DFT) was used to study the electrolyte solution
      effects on the oxygen reduction reaction (ORR) on Pt(111). To model the acid
      electrolyte, an H(5)O(2)(+) cluster was used. The vibrational proton oscillation
      modes for adsorbed H(5)O(2)(+) computed at 1711 and 1010 cm(-1), in addition to
      OH stretching and H(2)O scissoring modes, agree with experimental vibrational
      spectra for proton formation on Pt surfaces in ultrahigh vacuum. Using the
      H(5)O(2)(+) model, protonation of adsorbed species was found to be facile and
      consistent with the activation barrier of proton transfer in solution. After
      protonation, OOH dissociates with an activation barrier of 0.22 eV, similar to
      the barrier for O(2) dissociation. Comparison of the two pathways suggests that
      O(2) protonation precedes dissociation in the oxygen reduction reaction.
      Additionally, an OH diffusion step following O protonation inhibits the reaction,
      which may lead to accumulation of oxygen on the electrode surface.

PMID- 16884254
TI  - Dynamics of ion exchange between self-assembled redox polyelectrolyte multilayer
      modified electrode and liquid electrolyte.
AB  - A probe beam deflection (PBD) study of ion exchange between an electroactive
      polymer poly(allylamine)-bipyridyl-pyridine osmium complex film and liquid
      electrolyte is reported. The PBD measurements were made simultaneously to
      chronoamperometric oxidation-reduction cycles, to be able to detect kinetic
      effects in the ion exchange. Layer-by-layer (LbL) self-assembled redox
      polyelectrolyte films with osmium bipyridyl complex covalently attached to
      poly(allylamine) (PAH-Os) and poly(styrene sulfonate) (PSS) have been built by
      alternate electrostatic adsorption from soluble polyelectrolytes. The ionic
      exchange during initial conditioning of the film ("break-in") undergoing
      oxidation-reduction cycles and recovery after equilibration in the reduced state
      have shown an exchange of anions and cations with time lag between them. The
      effect of the nature of cation on the ionic exchange has been investigated with
      dilute HCl, LiCl, NaCl, and CsCl electrolytes. The ratio of anion to cation
      exchanged at the film-electrolyte interface has a strong dependence on the nature
      of charge in the topmost layer, that is, when negatively charged PSS is the
      capping layer, a larger proportion of cation exchange is observed. This
      demonstrates that the electrical potential distribution at the redox
      polyelectrolyte multilayer (PEM)/electrolyte interface determines the ionic flux
      in response to charge injection in the film.

PMID- 16884255
TI  - Pt-Ru supported on double-walled carbon nanotubes as high-performance anode
      catalysts for direct methanol fuel cells.
AB  - Pt-Ru supported on carbon nanotubes (CNTs) (single-walled nanotubes, double
      walled nanotubes (DWNTs), and multi-walled nanotubes) catalysts are prepared by
      an ethylene glycol reduction method. Pt-Ru nanoparticles with a diameter of 2-3
      nm and narrow particle size distributions are uniformly deposited onto the CNTs.
      A simple and fast filtration method followed by a hot-press film transfer is
      employed to prepare the anode catalyst layer on a Nafion membrane. The Pt
      Ru/DWNTs catalyst shows the highest specific activity for methanol oxidation
      reaction in rotating disk electrode experiments and the highest performance as an
      anode catalyst in direct methanol fuel cell (DMFC) single cell tests. The DMFC
      single cell with Pt-Ru/DWNTs (50 wt %, 0.34 mg Pt-Ru/cm(2)) produces a 68%
      enhancement of power density, and at the same time, an 83% reduction of Pt-Ru
      electrode loading when compared to Pt-Ru/C (40 wt %, 2.0 mg Pt-Ru/cm(2)).

PMID- 16884256
TI  - Ultrathin wagon-wheel-like TiOx phases on Pt(111): a combined low-energy electron
      diffraction and scanning tunneling microscopy investigation.
AB  - Ultrathin ordered titanium oxide films on a Pt(111) surface have been prepared by
      reactive deposition and characterized by low-energy electron diffraction and
      scanning tunneling microscopy (STM). According to the postdeposition annealing
      condition, three different phases have been prepared which show a wagon-wheel
      like (hereafter ww) morphological pattern. Two of them can be prepared as single
      phases (w- and w'-TiO(x)) and one (w(int)-TiO(x)) as a mixed phase which always
      coexists with at least one of the other two phases. All of them are formed by a
      Ti-O bilayer, where the Ti atoms are located at the interface with the substrate,
      but they show a rather distinct STM ww pattern. The experimental STM contrast has
      been discussed on the basis of a Moire-like model, i.e., as deriving from a
      modulation of the Ti occupancy of the different substrate sites (i.e., hollow,
      bridge and on-top sites). The major part of the STM data can be easily
      interpreted on the basis of this simplified model.

PMID- 16884257
TI  - Adsorption and activation of CO over flat and stepped Co surfaces: a first
      principles analysis.
AB  - The adsorption and activation of CO over flat Co{0001}, corrugated Co{1120}, and
      stepped Co{1012} and Co{1124} surfaces have been analyzed using periodic density
      functional theory calculations. CO strongly chemisorbs on all these surfaces but
      does not show a strong dependence on the surface structure. The calculated
      structure of adsorbed CO on Co{0001} at 1/3 monolayer (ML) of coverage was found
      to be in good agreement with the experiment. The barrier for CO dissociation over
      Co{0001} was found to decrease with decreasing CO coverage, taking on a value of
      232 kJ/mol at 1/4 ML and 218 kJ/mol at 1/9 ML. The presence of the "zigzag"
      channel on Co{1120} enhances the reactivity slightly by reducing the barrier for
      CO dissociation to 195 kJ/mol. In contrast, the stepped Co{1012} and Co{1124}
      surfaces are much more active than the flat and corrugated surfaces. Both stepped
      surfaces provide direct channels for CO dissociation that do not have barriers
      with respect to gas-phase CO. In general the activation barriers lower as the
      reaction energies become more exothermic. Reconstruction of the step edges that
      occur in the product state, however, prevents a linear correlation between the
      reaction energy and the activation energy.

PMID- 16884258
TI  - An optical waveguide study on the nanopore formation in block
      copolymer/homopolymer thin films by selective solvent swelling.
AB  - Thin films of mixtures of asymmetric poly(styrene-block-methyl methacrylate) (PS
      b-PMMA) diblock copolymers and PMMA homopolymers with cylindrical PMMA
      microdomains oriented normal to the substrate surface were used to couple optical
      modes in the Kretschmann configuration, and their optical properties were
      investigated by optical waveguide spectroscopy (OWS). The nanopore formation in
      the block copolymer (BCP) waveguide layer via selective solvent swelling and
      subsequent reannealing was monitored in terms of shifts in the coupling mode
      angles. The sequential swelling/reannealing of the initial mixture film resulted
      in a number of discrete or partially interconnected pores instead of cylindrical
      pores with a high aspect ratio. The simultaneous processes occurring inside and
      on top of the BCP waveguide layer were discerned independently with high
      selectivity for p- and s-polarization.

PMID- 16884259
TI  - Water absorption and desorption from the dipole ordered polymer
      poly(methylvinylidene cyanide).
AB  - From thermal desorption studies, we find evidence that absorbed water in the bulk
      of poly(methylvinylidene cyanide) is more weakly bound than is the case for
      copolymer films of poly(vinylidenefluoride-trifluoroethylene). Ultraviolet laser
      enhanced thermal desorption of absorbed water exhibits little light polarization
      dependence for poly(methylvinylidene cyanide) in contrast to absorbed water in
      copolymer films of poly(vinylidenefluoride-trifluoroethylene). The implications
      of these differences are discussed.

PMID- 16884261
TI  - Influence of pyrene-labeling on fluid lipid membranes.
AB  - We elucidate the influence of pyrene-labeled phospholipids on the structural
      properties of a fluid dipalmitoylphosphatidylcholine lipid membrane. To this end,
      we employ extensive atomic-scale molecular dynamics simulations with varying
      concentrations of pyrene-linked lipids. We find pyrene labeling to perturb the
      membrane structure significantly in the vicinity of the probe, the correlation
      length in the bilayer plane being about 1.0-1.5 nm. The local perturbations lead
      to enhanced ordering and packing of lipid acyl chains located in the vicinity of
      the probe. Surprisingly, this holds true not only for lipids that reside in the
      same leaflet as the pyrene-labeled probe but also for lipids in the opposite
      monolayer. The latter is due to substantial interdigitation of the pyrene moiety
      into the opposite leaflet, suggesting that occasional excimer formation may take
      place for probes in different leaflets. As a related issue, we also discuss the
      location and conformational orientation of the pyrene moieties. In particular,
      the orientational distribution of pyrene turns out to be more broad and diverse
      than the distribution of the corresponding acyl tails of nonlabeled lipids.

PMID- 16884260
TI  - Chain-length effects on molecular conformation in and chirality of self-assembled
      monolayers of alkoxylated benzo[c]cinnoline derivatives on highly oriented
      pyrolytic graphite.
AB  - Self-assembled structures of alkoxylated benzo[c]cinnoline derivatives prepared
      on highly oriented pyrolytic graphite at room temperature from their solutions in
      solvents such as 1-phenyloctane, toluene, and 1-octanol were studied by scanning
      tunneling microscopy. The alkoxy chain length markedly affected the molecular
      conformations in 2-dimensional assemblies of these derivatives. Long-chain
      derivatives adopted the trans conformations more often than cis, whereas short
      chain derivatives took exclusively the cis conformations in the self-assembled
      monolayers (SAMs). For the derivatives of intermediate chain lengths,
      polymorphism existed, with four molecular conformations identified
      experimentally. Experimental evidence substantiated the formation of chiral SAM
      structures at the surface, which can be explained by the conformations of the
      molecules. The chirality was also affected by the chain length of the molecules.
      A simple method analyzing the angles between different domains in the SAMs was
      used to identify the molecular conformations and to predict their relative
      structures.

PMID- 16884262
TI  - Acidity adjustment of HZSM-5 zeolites by dealumination and realumination with
      steaming and citric acid treatments.
AB  - This article describes a novel method for acidity adjustment of HZSM-5 zeolites
      with steaming and citric acid treatments and demonstrates the realumination
      effect of citric acid on HZSM-5 zeolites dealuminated by steaming. A series of
      modified HZSM-5 zeolites were prepared by streaming and/or acid treatments and
      characterized by means of X-ray diffraction (XRD), X-ray fluorescence
      spectroscopy (XRF), (27)Al MAS NMR spectroscopy, hydroxyl infrared spectroscopy
      (OH-IR), pyridine-adsorbed infrared spectroscopy, and N(2) adsorption in the
      present investigation. The results showed that compared with single HCl or citric
      acid treatment, steaming treatment, and steaming/HCl treatments, citric acid
      treatment after steaming exclusively increased the amount of framework Al due to
      reinsertion of extraframework Al into the defective sites of the steamed HZSM-5
      framework. This realumination effect of the citric acid treatment on the steamed
      HZSM-5 zeolite, which is reported here for the first time to the best of our
      knowledge, could nearly recover the pore structure of the steamed zeolite to that
      of the parent HZSM-5 zeolite and appropriately tailor the amount and strength of
      different acid sites, which sheds light on optimizing the physicochemical
      properties of HZSM-5 zeolites. It was also found that the steaming treatment
      prior to the citric acid treatment was the precondition of the realumination of
      HZSM-5 zeolites, suggesting that the lattice defect sites generated during
      steaming were necessary for citric acid to work.

PMID- 16884263
TI  - Silica-supported Au nanoparticles decorated by TiO2: formation, morphology, and
      CO oxidation activity.
AB  - Au-TiO(2) interface on silica support was aimed to be produced in a controlled
      way by use of Au hydrosol. In method A, the Au colloids were modified by
      hydrolysis of the water-soluble Ti(IV) bis(ammoniumlactato)dihydroxide (TALH)
      precursor and then adsorbed on Aerosil SiO(2) surface. In method B, Au sol was
      first deposited onto the SiO(2) surface and then TALH was adsorbed on it. Regular
      and high-resolution transmission electron microscopy (TEM and HRTEM) and energy
      dispersive spectrometry (EDS) analysis allowed us to conclude that, in method A,
      gold particles were able to retain the precursor of TiO(2) at 1.5 wt % TiO(2)
      loading, but at 4 wt % TiO(2) content the promoter oxide appeared over the silica
      surface as well. With method B, titania was detected on silica at each TiO(2)
      concentration. In Au-TiO(2)/SiO(2) samples, the stability of Au particles against
      sintering was much higher than in Au/TiO(2). The formation of an active Au-TiO(2)
      perimeter was proven by the greatly increased CO oxidation activity compared to
      that of the reference Au/SiO(2).

PMID- 16884264
TI  - Diffusion on a self-assembled monolayer: molecular modeling of a bound + mobile
      lubricant.
AB  - The diffusion of tricresyl phosphate molecules on an octadecyltrichlorosilane
      self-assembled monolayer (SAM) was characterized using molecular dynamics
      simulations. The simulations predict that when placed on the top of a close
      packed SAM, the molecules remain mobile on the surface with an isotropic
      diffusion activation energy of approximately 9 kJ/mol. In contrast, an
      anisotropic barrier that results from chain tilt within the SAM is predicted for
      diffusion into a defect created by reducing the alkane chain length within a
      cylinderical region of the surface. Once in the defect, the molecules become
      trapped by embedding part of the molecule into the side of the SAM.

PMID- 16884265
TI  - Electronic structure of methoxy-, bromo-, and nitrobenzene grafted onto Si(111).
AB  - The properties of Si(111) surfaces grafted with benzene derivatives were
      investigated using ultraviolet photoemission spectroscopy (UPS) and X-ray
      photoelectron spectroscopy (XPS). The investigated materials were nitro-, bromo-,
      and methoxybenzene layers (-C(6)H(4)-X, with X = NO(2), Br, O-CH(3)) deposited
      from diazonium salt solutions in a potentiostatic electrochemical process. The
      UPS spectra of the valence band region are governed by the molecular orbital
      density of states of the adsorbates, which is modified from the isolated state in
      the gas phase due to molecule-molecule and molecule-substrate interaction.
      Depending on the adsorbate, clearly different emission features are observed. The
      analysis of XPS intensities clearly proves multilayer formation for bromo- and
      nitrobenzene in agreement with the amount of charge transferred during the
      grafting process. Methoxybenzene forms only a sub-monolayer coverage. The
      detailed analysis of binding energy shifts of the XPS emissions for determining
      the band bending and the secondary electron onset in UPS spectra for determining
      the work function allow one to discriminate between surface dipole layers-
      changing the electron affinity--and band bending, affecting only the work
      function. Thus, complete energy band diagrams of the grafted Si(111) surfaces can
      be constructed. It was found that silicon surface engineering can be accomplished
      by the electrochemical grafting process using nitrobenzene and bromobenzene:
      silicon-derived interface gap states are chemically passivated, and the adsorbate
      related surface dipole effects an increase of the electron affinity.

PMID- 16884266
TI  - Water-hydrocarbon interfaces: effect of hydrocarbon branching on interfacial
      structure.
AB  - Molecular dynamics simulation are performed for the water/hydrocarbon system to
      study the effect of hydrocarbon branching on interfacial properties. The
      following two series of hydrocarbons are considered: (1) n-pentane, 2-methyl
      pentane, and 2,2,4-trimethyl pentane (constant chain length) and (2) n-octane, 2
      methyl heptane, and 2,2,4-trimethyl pentane (constant molecular mass). With a
      simple algorithm for identification of surface sites and mapping nonsurface sites
      to these surface sites, intrinsic profiles were constructed with respect to the
      surface layer. Intrinsic density profiles for water and hydrocarbons with respect
      to the hydrocarbon and water surface, respectively, resemble density profiles of
      liquids in the presence of a wall. Order parameters were used to study
      orientation of molecules with respect to the surface normal and the hydrogen bond
      network was characterized in terms of the number of hydrogen bonds per water
      molecule and percentage of hydrogen bonded molecules in the first coordination
      shell. The corresponding intrinsic profiles were obtained. The O-H bond for
      surface water was found to have two preferential orientations, pointing toward
      the hydrocarbon phase and parallel to the interface. Hydrocarbon molecules in
      series 1 orient along the interface with the more branched molecule better
      aligned. For molecules in series 2, the larger molecular length reduces the
      alignment of molecules along the interface.

PMID- 16884267
TI  - Role of kinetics in the selective surface oxidations of transition metal
      carbides.
AB  - The different oxidation behavior of TiC and VC(100) surfaces by molecular oxygen
      has been investigated by density functional theory with a slab model. From the
      thermodynamic stability of the final states that involve dissociated O(2), one
      cannot well explain the experimental observations. Two different oxidation
      pathways of TiC and VC(100) surfaces have been explored in this work, and the
      results indicate that two channels share the same precursor state. However, from
      the precursor, only the pathway leading to the formation of a C-O bond is
      energetically feasible for the TiC(100) surface, while on VC(100) the O atoms
      tend to occupy the metal surface sites due to a smaller energy barrier for this
      channel. Further band structure calculations reveal that the additional d
      electron of V atom favors the stability of the molecularly adsorbed species. The
      oxidation mechanism unveiled from the present calculations clearly evidences that
      the kinetic effects introduced by one additional d electron of the V atom play a
      crucial role in explaining the different surface chemistry between TiC and VC
      (100) surfaces.

PMID- 16884268
TI  - Microwaves and sorption on oxides: a surface temperature investigation.
AB  - Microwave heating is not the same as conventional heating, and it is believed
      that this difference, the "microwave effect," may be interpreted to be due to
      selective, local heating. The temperature at the surface where sorption occurs is
      "effectively" greater than the measured solid or gas temperature. In these
      studies, measurements of the amounts of adsorption as functions of the partial
      pressures of a specific adsorbate in the presence of microwave irradiation were
      related to the conventional adsorption isotherms. Equating the adsorbate pressure
      required to achieve a specific coverage (an isostere) in the presence of
      microwave irradiation to the amount adsorbed for a conventional isotherm allowed
      for an estimate of the "effective" surface temperature in the presence of
      microwaves. It was found that the effective surface temperature increased when
      using adsorbates having a higher permittivity or when increasing the microwave
      power. The implication of this change in the surface energy for specific species
      in the presence of microwaves is discussed.

PMID- 16884269
TI  - Experimental and theoretical investigation of the stability of Pt-3d-Pt(111)
      bimetallic surfaces under oxygen environment.
AB  - The stability of the Pt-3d-Pt(111) (3d = Ti, V, Cr, Mn, Fe, Co, or Ni) bimetallic
      surface structures in the presence of adsorbed oxygen has been investigated by
      means of density functional theory (DFT). The dissociative binding energies of
      oxygen on Pt-3d-Pt(111) (i.e., subsurface 3d monolayer) and 3d-Pt-Pt(111) (i.e.,
      surface 3d monolayer) were calculated. All of the Pt-3d-Pt(111) surfaces were
      found to have weaker oxygen binding energies than pure Pt(111) whereas all of the
      3d-Pt-Pt(111) surfaces were found to have stronger oxygen binding energies than
      pure Pt(111). The total heat of reaction was calculated for the segregation for
      3d metal atoms from Pt-3d-Pt(111) to 3d-Pt-Pt(111) when exposed to a half
      monolayer of oxygen. All of the Pt-3d-Pt(111) subsurface structures were
      predicted to be thermodynamically unstable with adsorbed oxygen. In addition, the
      segregation of subsurface Ni and Co to the surfaces of Pt-Ni-Pt(111) and Pt-Co
      Pt(111) was investigated experimentally using Auger electron spectroscopy (AES)
      and high-resolution electron energy loss spectroscopy (HREELS). AES and HREELS
      confirmed the trend predicted by DFT modeling and showed that both the Pt-Ni
      Pt(111) and Pt-Co-Pt(111) surface structures were unstable in the presence of
      adsorbed oxygen. The activation barrier of the segregation of surbsurface Ni and
      Co atoms was determined to be 15 +/- 2 and 7 +/- 1 kcal/mol, respectively. These
      results are further discussed for their implication in the design and selection
      of cathode bimetallic electrocatalysts for the oxygen reduction reaction (ORR) in
      polymer electrode membrane (PEM) fuel cells.

PMID- 16884271
TI  - Solvation of ions in hydrophilic layer of polyoxyethylated nonionic micelle.
      Cooperative approach by electrophoresis and ion-transfer voltammetry.
AB  - Electrophoretic measurements of micellar mobility have revealed that
      polyoxyethylated nonionic surfactant micelles have negative zeta potential in
      various electrolytes, indicating that the partition of anions into the micelle
      dominates the entire electrolyte partition and the induced surface potential of
      the micelle. Although an excess of a negative charge is thus revealed in the
      micelle, it is uncertain whether anions are preferably solvated in the micelles
      or cations are expelled from the micelles. To determine the solvation energies of
      single ions in the hydrophilic layer of the micelle, we have performed ion
      transfer voltammetric measurements at microinterfaces between nitrobenzene and
      aqueous tetraethyleneglycol solution, which acts as a model for the palisade
      layer of the micelles. The cooperative utilization of these different methods has
      allowed us to determine the Gibbs free energy of transfer of a single ion without
      an extrathermodynamic assumption. On the basis of the resulting values, the
      partition of ions and the zeta potential induced by the imbalance of anionic and
      cationic partition have been quantitatively explained.

PMID- 16884270
TI  - Effect of synthesis parameters on the chromium content and catalytic activities
      of mesoporous Cr-MSU-x prepared under acidic conditions.
AB  - A series of chromium-incorporated MSU-x mesoporous molecular sieves were
      synthesized under different templates, initial Si/Cr molar ratios, aging times,
      and temperatures in acid solution. The synthesis was performed by using sodium
      silicate, chromium nitrate, and nonionic poly(ethylene oxide) surfactant as the
      source of silicone, metal, and the template, respectively. The Cr-MSU-x products
      were analyzed by inductively couple plasma-optical emission spectrometry to
      determine the actual Cr content and were characterized by X-ray diffraction, N(2)
      adsorption-desorption, scanning electron microscopy, high-resolution transmission
      electron microscopy, diffuse reflectance UV-visible, X-ray adsorption near-edge
      spectroscopy, and temperature-programmed reduction techniques. The Cr species
      were mostly formed as Cr(VI) in tetrahedral coordination. Two kinds of Cr(VI)
      species with different reduction abilities were distinguished. The catalytic
      activities of Cr-MSU-x in the dehydrogenation of ethane to ethylene with CO(2)
      were investigated at the same time. The synthesis parameters explored strongly
      influence the chromium content in Cr-MSU-x and, subsequently, the catalytic
      activities. The Cr-MSU-x synthesized with Si/Cr = 20, aging at 25 degrees C for
      22 h, and templating by fatty alcohol polyoxyethylene ether gave the best
      activities, resulting in 58.0% ethane conversion and 92.1% ethylene selectivity.
      The Cr species in Cr-MSU-x are more efficient in activating and converting ethane
      molecules than are conventional catalysts.

PMID- 16884272
TI  - In situ stress and nanogravimetric measurements during underpotential deposition
      of bismuth on (111)-textured Au.
AB  - The surface stress associated with the underpotential deposition (upd) of bismuth
      on (111)-textured Au is examined, using the wafer curvature method, in acidic
      perchlorate and nitrate supporting electrolyte. The surface stress is correlated
      to Bi coverage by independent nanogravimetric measurements using an
      electrochemical quartz crystal nanobalance. The mass increase measured in the
      presence of perchlorate is consistent with the (2 x 2) and (p x square root 3)
      2Bi adlayers reported in the literature. ClO(4)(-) does not play a significant
      role in the upd process. The complete Bi monolayer causes an overall surface
      stress change of about -1.4 N m(-1). We attribute this compressive stress to the
      formation of Bi-Au bonds which partially satisfy the bonding requirements of the
      Au surface atoms, thereby reducing the tensile surface stress inherent to the
      clean Au surface. At higher Bi coverage, an additional contribution to the
      compressive stress is due to the electrocompression of the (p x square root 3)
      2Bi adlayer. In nitric acid electrolyte, NO(3)(-) coadsorbs with Bi over the
      entire upd region but has little fundamental impact on adlayer structure and
      stress.

PMID- 16884273
TI  - Influence of water on the surface of the water-miscible ionic liquid 1-butyl-3
      methylimidazolium tetrafluoroborate: a sum frequency generation analysis.
AB  - Sum frequency generation spectroscopy (SFG) was used to study the influence of
      water on the surface of the water-miscible ionic liquid 1-butyl-3
      methylimidazolium tetrafluoroborate. The orientation of the cation at the gas
      liquid interface was analyzed as a function of ionic liquid concentration in
      water for concentrations from 0 to 1 mole fraction of the ionic liquid. The
      cation was found to be oriented with the imidazolium ring nearly parallel to the
      surface plane with a tilt angle > or = 70 degrees when the ionic liquid was dry.
      Furthermore, no noticeable change in the orientation was observed when high
      concentrations of water were mixed with the ionic liquid. The cation butyl chain
      is projecting into the gas phase with a CH(3) tilt angle of 54 +/- 2 degrees when
      the ionic liquid is dry and 46 +/- 4 degrees when mixed with water. Water is
      oriented at the surface only for concentration < or = 0.02 mole fraction of the
      ionic liquid. At higher ionic liquid concentrations (mole fractions > or = 0.05)
      the gas-liquid interface resembles that of the pure ionic liquid.

PMID- 16884274
TI  - Sum-frequency spectroscopy analysis of two-component langmuir monolayers and the
      associated interfacial water structure.
AB  - Sum-frequency spectroscopy (SFS) in the CH and OH stretching regions was employed
      to obtain structural information about Langmuir monolayers on the H(2)O subphase
      of the model lipid dioctadecyldimethylammonium bromide (DOMA) and of the neutral
      surfactant methyl stearate (SME) and their mixtures and about the interfacial
      water structure underneath the films. These results were compared with the sum
      frequency spectra of the interface between Langmuir monolayers of stearic acid
      and stearic acid-DOMA monolayers and water to prove that the uncompensated
      headgroup charge of DOMA at the interface is the reason for structuring of
      interfacial water close to the studied monomolecular films. Sum-frequency spectra
      on D(2)O subphase were also studied to account for the interference between the
      CH and OH spectral signatures because of the coherent nature of the SFS signals.
      Interfacial water structure proved to be a determining factor in the behavior of
      the mixed lipid monolayers. A mixing induced amplification in the surface
      potential DeltaV observed in our previous work was explained with total increase
      of the dipole moment for the mixed films, bigger than the arithmetic average for
      DOMA and SME monolayers alone. The increase is due to the better packing of the
      molecules in the mixed films and to the decrease in the interfacial water dipole
      moment arising from a more disordered water structure underneath the mixed
      monolayers.

PMID- 16884275
TI  - Toward efficient chemical potential calculations by expanded ensemble
      simulations; to make the free energy pathway fairly level.
AB  - A scheme is suggested of how to construct good bias potentials ("balancing
      factors") to be used in expanded ensemble (EE) calculations of chemical
      potentials of solutions. A combination of two strategies are used: (i) to use a
      pathway for particle insertions that avoids large variations in free energy and
      (ii) to use calculated free energy derivatives to construct a bias potential that
      makes the pathway fairly level. Only a few very short simulations are needed to
      accomplish the latter, and then, a full EE simulation is done to obtain the
      chemical potential. By practical calculations of the chemical potential of
      benzene, cyclohexane, and benzylamine in water, it is shown that this method is
      at least equally efficient to the recent adaptive EE (AEE) method by Aberg et al.
      (J. Chem. Phys. 2004, 120, 3370). Furthermore, the new method provides an
      alternative strategy that complements existing EE methods.

PMID- 16884276
TI  - Molecular dynamics study of polarizability anisotropy relaxation in aromatic
      liquids and its connection with local structure.
AB  - The collective polarizability anisotropy dynamics in a set of three aromatic
      liquids, benzene (Bz), hexafluorobenzene (HFB), and 1,3,5-trifluorobenzene (TFB),
      has been studied by molecular dynamics simulation. These liquids have very
      similar shapes, but different electrostatic interactions due to opposite
      polarities of C-H and C-F bonds, giving rise to different local intermolecular
      structures in the liquid phase. We have investigated how these structural
      arrangements affect polarizability anisotropy dynamics observed in optical Kerr
      effect (OKE) spectroscopy. We have modeled the interaction-induced polarizability
      with the first-order dipole-induced dipole approximation, with the molecular
      polarizability distributed over the carbon sites. Local contributions to the
      librational OKE spectrum were computed separately for molecules participating in
      parallel or perpendicular relative orientations within the first coordination
      shell. We found that the relative locations of parallel and perpendicular
      librational bands of the OKE spectra are closely related to the corresponding
      pair energy distributions of the closest four neighbors of a given molecule,
      corresponding to a model of a harmonic oscillator in a cage of nearest neighbors.
      This model predicts higher librational frequencies for more attractive
      intermolecular interactions, which in all three liquids correspond to parallel
      local arrangements. On the diffusive orientational time scale, all three liquids
      exhibit slower relaxation of molecules in parallel arrangements, although the
      difference in relaxation rates is substantial only in TFB, which has the
      strongest tendency toward parallel stacking. The analysis of the collective
      polarizability relaxation was performed using two different approaches, the
      projection scheme (J. Chem. Phys. 1980, 72, 2801) and the theory developed by
      Steele (Mol. Phys. 1987, 61, 1031) for the second time derivatives applied to
      collective time correlations. Both approaches allow the decomposition of the OKE
      response into contributions from orientational relaxation and other dynamical
      processes. We find that they lead to different predictions on how the response
      depends on collective reorientation and processes arising from fluctuations in
      the interaction-induced polarizability. We discuss the reasons for these
      differences and the advantages and disadvantages of the two analysis schemes.

PMID- 16884277
TI  - Determining the radius and the apparent charge of a micelle from electrical
      conductivity measurements by using a transport theory: explicit equations for
      practical use.
AB  - We propose here a procedure which combines experiments and simple analytical
      formulas that allows us to determine good estimations of the size and charge of
      ionic micelles above the critical micellar concentration (cmc). First, the
      conductivity of n-tetradecyltrimethylammonium bromide and chloride (TTABr and
      TTACl, respectively) aqueous solutions was measured at 25 degrees C, before and
      above their cmc. Then, an analytical expression for the concentration dependence
      of the conductance of an ionic mixture with three species (monomers, micelles,
      and counterions) was developed and applied to the analysis of the experiments.
      The theoretical calculations use the mean spherical approximation (MSA) to
      describe equilibrium properties. Here, we propose new expressions for the
      electrical conductivity, adapted to the case of electrolytes that are
      dissymmetric in size, and applicable up to a total surfactant concentration of
      0.1 mol L(-1). Moreover, we show that they are good approximations of the
      corresponding numerical results obtained from Brownian dynamics simulations.
      Since the analytical formulas given in the present paper involve a small number
      of unknown parameters, they allow one to derive the size and charge of macroions
      in solution from conductivity measurements.

PMID- 16884278
TI  - Intermolecular interaction of myoglobin with water molecules along the pH
      denaturation curve.
AB  - A method of diffusion coefficient (D) measurement for proteins based on the
      pulsed laser-induced transient grating method using a photosensitive cross-linker
      was applied to the characterization of the pH denaturation process of holo- and
      apo-myoglobin (Mb) from the viewpoint of protein-water interaction. It was found
      that the pH denaturation curve monitored by D agrees quite well with that
      determined by the circular dichroism intensity for holo-Mb. This fact indicates
      that the changes in intermolecular interaction and the alpha-helix content occur
      simultaneously during the unfolding process. However, the pH dependence of D for
      apo-Mb was different from that of alpha-helix content. This different behavior
      can be explained in terms of the different denaturation steps for the secondary
      structure and the hydrogen bonding network of the intermediate species around pH
      4; i.e., this intermediate is partially unfolded, but the hydrogen bonding
      network is dominantly an intramolecular one. Taking previously reported
      properties of this species into account, we conclude that water molecules are
      trapped in the hydrophobic core of the apo-Mb pH 4 intermediate. This fact
      suggests that the kinetic intermediate state of the protein folding process is a
      swollen state without water molecular exchange with the bulk phase.

PMID- 16884279
TI  - Mechanism of carotenoid singlet excited state energy transfer in modified
      bacterial reaction centers.
AB  - Ultrafast transient laser spectroscopy has been used to investigate carotenoid
      singlet excited state energy transfer in various Rhodobacter (Rb.) sphaeroides
      reaction centers (RCs) modified either genetically or chemically. The pathway and
      efficiency of energy transfer were examined as a function of the structures and
      energies of the donor and acceptor molecules. On the donor side, carotenoids with
      various extents of pi-electron conjugation were examined. RCs studied include
      those from the anaerobically grown wild-type strain containing the carotenoid
      spheroidene, which has 10 conjugated carbon-carbon double bonds; the GA strain
      containing neurosporene, which has nine conjugated double bonds; and aerobically
      grown wild-type cells, as well as aerobically grown H(M182)L mutant, both
      containing the carbonyl-containing carotenoid spheroidenone, which has 11
      conjugated double bonds. By varying the structure of the carotenoid, we observed
      the effect of altering the energies of the carotenoid excited states on the rate
      of energy transfer. Both S(1)- and S(2)-mediated carotenoid-to
      bacteriochlorophyll energy transfer processes were observed. The highest transfer
      efficiency, from both the S(1) and S(2) states, was observed using the carotenoid
      with the shortest chain. The S(1)-mediated carotenoid-to- bacteriochlorophyll
      energy transfer efficiencies were determined to be 96%, 84%, and 73% for
      neurosporene, spheroidene, and spheroidenone, respectively. The S(2)-mediated
      energy transfer efficiencies follow the same trend but could not be determined
      quantitatively because of limitations in the time resolution of the
      instrumentation. The dependence of the energy transfer rate on the energetics of
      the energy transfer acceptor was verified by performing measurements with RCs
      from the H(M182)L mutant. In this mutant, the bacteriochlorophyll (denoted B(B))
      located between the carotenoid and the RC special pair (P) is replaced by a
      bacteriopheophytin (denoted phi(B)), where the Q(X) and Q(Y) bands of phi(B) are
      1830 and 1290 cm(-1), respectively, higher in energy than those of B(B). These
      band shifts associated with phi(B) in the H(M182)L mutant significantly alter the
      spectral overlap between the carotenoid and phi(B), resulting in a significant
      decrease of the transfer efficiency from the carotenoid S(1) state to phi(B).
      This leaves energy transfer from the carotenoid S(2) state to phi(B) as the
      dominant channel. Largely because of this change in mechanism, the overall
      efficiency of energy transfer from the carotenoid to P decreases to less than 50%
      in this mutant. Because the spectral signature of phi(B) is different from that
      of B(A) in this mutant, we were able to demonstrate clearly that the carotenoid
      to-P energy transfer is via phi(B). This finding supports the concept that, in
      wild-type RCs, the carotenoid-to-P energy transfer occurs through the cofactor
      located at the B(B) position.

PMID- 16884280
TI  - Comprehensive study of the effects of methylation on tautomeric equilibria of
      nucleic acid bases.
AB  - Minor tautomers of nucleic acid bases can result by intramolecular proton
      transfer. These rare tautomers could be stabilized through the addition of methyl
      groups to DNA bases. A comprehensive theoretical study of tautomers of methylated
      derivatives of guanine, adenine, cytosine, thymine, and uracil was performed.
      Molecular geometries of all tautomers were obtained at the density functional
      theory and MP2 levels with the 6-31G(d,p) basis set, and single-point
      calculations were performed at the CCSD(T)/6-311G(d,p) level. Tautomers obtained
      by protonation at the preferred protonation site for methylated isolated bases
      were compared to their nonmethylated counterparts. The effects of methylation on
      the relative stabilities of nucleic acid base tautomers are also studied and
      discussed in this work. The results suggest that some sites on the bases may not
      be mutagenic and may even stabilize the canonical Watson-Crick form. The results
      also indicate that a number of methylation sites can stabilize the tautomers,
      suggesting possible mechanisms for mutagenic changes.

PMID- 16884281
TI  - Interaction of the sugars trehalose, maltose and glucose with a phospholipid
      bilayer: a comparative molecular dynamics study.
AB  - Molecular dynamics simulations are used to investigate the interaction of the
      sugars trehalose, maltose, and glucose with a phospholipid bilayer at atomic
      resolution. Simulations of the bilayer in the absence or in the presence of sugar
      (2 molal concentration for the disaccharides, 4 molal for the monosaccharide) are
      carried out at 325 and 475 K. At 325 K, the three sugars are found to interact
      directly with the lipid headgroups through hydrogen bonds, replacing water at
      about one-fifth to one-quarter of the hydrogen-bonding sites provided by the
      membrane. Because of its small size and of the reduced topological constraints
      imposed on the hydroxyl group locations and orientations, glucose interacts more
      tightly (at identical effective hydroxyl group concentration) with the lipid
      headgroups when compared to the disaccharides. At high temperature, the three
      sugars are able to prevent the thermal disruption of the bilayer. This protective
      effect is correlated with a significant increase in the number of sugar
      headgroups hydrogen bonds. For the disaccharides, this change is predominantly
      due to an increase in the number of sugar molecules bridging three or more lipid
      molecules. For glucose, it is primarily due to an increase in the number of sugar
      molecules bound to one or bridging two lipid molecules.

PMID- 16884282
TI  - Electronic coupling between heme electron-transfer centers and its decay with
      distance depends strongly on relative orientation.
AB  - A method for calculating the electron-transfer matrix element V(RP) using density
      functional theory Kohn-Sham orbitals is presented and applied to heme dimers of
      varying relative orientation. The electronic coupling decays with increased iron
      separation according to V(RP) = V(0)(RP)exp(-beta r/2) with a distance dependence
      parameter beta approximately 2 A(-1) for hemes with parallel porphyrins and
      either 1.1 or 4.0 A(-1) when the porphyrin planes are perpendicular, depending on
      the alignment of the iron d(pi) orbital. These findings are used to interpret the
      observed orientation of the hemes in tetraheme redox proteins such as
      Flavocytochrome c(3) fumarate reductase (Ifc(3), PDB code 1QJD) of Shewanella
      frigidimarina, another flavocytochrome from the same bacterium (Fcc(3), 1E39) and
      a small tetraheme cytochrome of Shewanella oneidensis strain MR1 (1M1P). Our
      results show that shifting and rotating the hemes controls the adiabaticity of
      the three electron hopping steps.

PMID- 16884283
TI  - Role of sequence and conformation on the photochemistry and the photophysics of A
      T DNA dimers: an experimental and computational approach.
AB  - The role of base sequence and conformation on the photochemistry and photophysics
      of thymidylyl (3'-5')-2'-deoxyadenosine sodium salt (TpdA) and 2-deoxyadenylyl
      (3'-5')-thymidine ammonium salt (dApT) was studied. To this end, nanosecond
      transient absorption at 266 nm, steady-state irradiation at 254 nm, and quantum
      chemical calculations were used. The transient absorption spectra show the
      solvated electron broad band in the visible region for each dinucleotide. In
      addition, low-intensity absorption bands are observed in the UV region, which are
      attributed to the deprotonated and protonated neutral radicals of adenine and
      thymine bases. Photoionization (PI) occurs by one- and two-photon pathways; the
      latter accounting for approximately 70% of the net PI yield. A diffusion-limited
      rate constant of 2.0 x 10(10) M(-1) s(-1) was obtained for the reaction of the
      neutral molecule with the photoejected electron in both sequences. The
      photodestruction yield, measured from the chromophore loss at 260 nm, decreases
      in the presence of well-known electron scavengers. This suggests the
      participation of base radical anions as one of the photodegradation pathways,
      which is higher in TpdA than in dApT. The intermediacy of a radical ion pair
      (charge separated state) between the adjacent adenine and thymine bases is
      proposed in the formation of the [2 + 2] cycloadduct intermediate. The [2 + 2]
      cycloadduct intermediate is known to be the precursor of the thymine-adenine
      eight-member ring photoproduct (TA*). Conformational constrains in the radical
      ion pair are suggested to explain the absence of the TA* photoproduct in dApT.
      This hypothesis is supported by semiempirical calculations performed on all
      relevant reactive intermediates proposed to participate in the mechanism of
      formation of TA*. Altogether, the results show that sequence and conformation
      profoundly influence the photochemistry and the photophysics of these DNA model
      systems.

PMID- 16884284
TI  - Aggregation studies of the water-soluble gadofullerene magnetic resonance imaging
      contrast agent: [Gd@C82O6(OH)16(NHCH2CH2COOH)8]x.
AB  - The aggregation behavior of the newly synthesized gadofullerene magnetic
      resonance imaging (MRI) contrast agent, i.e.,
      Gd@C(82)O(6)(OH)(16)(NHCH(2)CH(2)COOH)(8) (abbreviated as AAD-EMF), was studied
      in detail by dynamic light scattering, scanning electron microscopy, T(1)
      weighted magnetic resonance, and atomic force microscopy. It was revealed that
      the AAD-EMF aggregation in aqueous solution is pH-dependent. At pH 2, the AAD-EMF
      first self-assemble to form ca. 30 nm small clusters, and then dozens of the
      small clusters further aggregate to form large grapelike particles. At pH 7, the
      aggregates are also ca. 30 nm small clusters, but they are hard to further
      aggregate except for forming some cluster dimers or trimers, so AAD-EMF
      aggregates have a narrow size distribution by this time. At pH 9, the AAD-EMF
      aggregations cover a large range of continuous hydrodynamic diameters from 30 to
      2000 nm. On the basis of the above observations, the aggregating mechanism of AAD
      EMF under different pH values was proposed by concurrently considering the
      hydrogen-bonding effect and the dipolar interactions between AAD-EMF.

PMID- 16884285
TI  - Configurational entropies of lipids in pure and mixed bilayers from atomic-level
      and coarse-grained molecular dynamics simulations.
AB  - Single-chain and single-fragment configurational entropies of lipid tails in
      hydrated lipid bilayers are evaluated from molecular dynamics simulations using
      the quasi-harmonic approximation. The entropy distribution along individual acyl
      tails is obtained and compared to that of corresponding hydrocarbon chains in the
      liquid phase. We consider pure dipalmitoylphosphatidylcholine and mixed
      dioleoylphosphatidylcholine/dioleoylphosphatidylethanolamine bilayers. The
      systems are modeled at different levels of spatial resolution: In an atomic-level
      (AL) model all (heavy) atoms are explicitly simulated; in a coarse-grained (CG)
      model particles (beads) representing groups of covalently bound atoms are used,
      which map approximately four non-hydrogen atoms to one interaction site. Single
      chain and single-fragment entropies and correlations between the motions of
      (single) acyl chains are compared. A good correspondence is found between the
      flexibility of the AL and CG models. The loss in configurational entropy due to
      the reduction in the number of degrees of freedom upon coarse-graining of the
      model is estimated. The CG model shows about 4 times faster convergence of the
      chain entropies than the more detailed AL model. Corrections to the quasi
      harmonic entropy estimates were found to be small for the CG model. For the AL
      model, the correction due to mode anharmonicities is small, but the correction
      due to pairwise (supralinear) mode correlations is sizable.

PMID- 16884286
TI  - Spectroscopic and semiempirical studies of a proton channel formed by the methyl
      ester of monensin A.
AB  - Monensin A is an ionophore able to carry protons and cations through the cell
      membrane. Its methyl ester (MON1) and its hydrates have been studied in
      acetonitrile, and its deuterated analogue by Fourier transform infrared (FTIR)
      and (1)H and (13)C NMR spectroscopies as well as by vapor pressure osmotic and
      PM5 semiempirical methods. Interestingly, these hydrates show new and unexpected
      biophysical and biochemical properties. The formation of the hydrates starts with
      a transfer of a proton from the O(IV)-H hydroxyl group of MON1 to an oxygen atom
      of a water molecule, which is subsequently hydrated by other water molecules
      forming the (MON1 + 3H(2)O) species. This hydrate exhibits a ringlike structure
      in which the water molecules form an almost linear hydrogen-bonded chain. Within
      this chain, the excess proton fluctuates very fast inside the water cluster as
      indicated by a continuous absorption in the FTIR spectra. The formation of the
      (MON1 + 3H(2)O) species is accompanied by a self-assembly process, leading to the
      formation of a proton channel made up of eight (MON1 + 3H(2)O) units with a
      length of 60 A, in which the proton can fluctuate over the whole distance.
      Semiempirical calculations suggest that due to the hydrophobic surface the
      channel can be incorporated readily in a lipid bilayer. This hypothetical new
      channel is thought to be able to transport protons through the cell membrane.
      Thus it is a suitable model for studying proton-transfer processes, and in
      addition, it may open interesting new fields of application.

PMID- 16884287
TI  - Density functional theory for charge transfer: the nature of the N-bands of
      porphyrins and chlorophylls revealed through CAM-B3LYP, CASPT2, and SAC-CI
      calculations.
AB  - While density functional theory (DFT) has been proven to be extremely useful for
      the prediction of thermodynamic and spectroscopic properties of molecules, to
      date most functionals used in common implementations of DFT display a systematic
      failure to predict the properties of charge-transfer processes. While this is
      explicitly manifest in Rydberg transitions of atoms and molecules and in
      molecular charge-transfer spectroscopy, it also becomes critical for systems
      containing extended conjugation such as polyenes and other conducting polymers,
      porphyrins, chlorophylls, etc. A new density functional, a Coulomb-attenuated
      hybrid exchange-correlation functional (CAM-B3LYP), has recently been developed
      specifically to overcome these limitations, and it has been shown to properly
      predict molecular charge-transfer spectra. Here, we demonstrate that it predicts
      qualitatively reasonable spectra for porphyrin, some oligoporphyrins, and
      chlorophyll. However, alternate density functionals developed to overcome the
      same limitations such as current-density functional theory are shown, in their
      present implementation, to remain inadequate. The CAM-B3LYP results are shown to
      be in excellent agreement with complete-active-space plus second-order Moller
      Plesset perturbation theory and symmetry-adapted cluster configuration
      interaction calculations: These depict the N and higher bands of porphyrins and
      chlorophylls as being charge-transfer bands associated with localization of
      molecular orbitals on individual pyrrole rings. The validity of the basic
      Gouterman model for the spectra of porphyrins and chlorophylls is confirmed,
      rejecting modern suggestions that non-Gouterman transitions lie close in energy
      to the Q-bands of chlorophylls. As porphyrins and chlorophylls provide useful
      paradigms for problems involving extended conjugation, the results obtained
      suggest that many significant areas of nanotechnology and biotechnology may now
      be realistically treated by cost-effective density-functional-based computational
      methods.

PMID- 16884288
TI  - Excited state behaviors of the dodecamolybdocerate (IV) anion:
      (NH4)6H2(CeMo12O42).9H2O.
AB  - The polyoxometalate (NH(4))(6)H(2)(CeMo(12)O(42)).9H(2)O (abbreviated as
      Ce(IV)Mo(12)) was synthesized, and its Ce(III) form was obtained by exhaustive
      electrochemical reduction. Both forms are fairly stable in pH 0.0 media. This
      stability decreases when the pH increases. The Ce(IV) species, in which the
      central metal is in the f(0) electronic configuration, is found to fluoresce, a
      feature that is only straightforwardly explained with the Ce(III) state. As the
      results of a series of experiments converge to confirm the stability of
      Ce(IV)Mo(12) in the media studied, a suggested rationale is that the emission
      originates from a higher-energy ligand-to-metal charge transfer and follows a
      scheme which is ultimately equivalent to the classical metal-centered
      fluorescence of Ce(III). Detailed studies of the influences of pH and ionic
      strength were carried out and suggest that protonated and/or ion-paired
      assemblies are the fluorescent species. A reproducible increase of the
      fluorescence intensity of Ce(IV)Mo(12) as a function of time was also observed.

PMID- 16884289
TI  - Novel, orally bioavailable gamma-aminoamide CC chemokine receptor 2 (CCR2)
      antagonists.
AB  - Through modification of a screening hit we have discovered a structurally
      distinct new lead, (2S)-N-[3,5-bis(trifluoromethyl)benzyl]-2-(4-fluorophenyl)-4
      (4-phenylpiperidin-1-yl)butanamide (11), which has subsequently served as the
      departure point for an ongoing program targeting CCR2 antagonists. Optimization
      of 11 leading to antagonists 26 and 37 is described. Antagonist 26 was shown to
      have good oral bioavailability in rats. Antagonist 37 had a CCR2 IC50 of 59 nM
      and excellent potency in a functional assay measuring inhibition of MCP-1 induced
      monocyte chemotaxis (IC50 of 41 nM).

PMID- 16884290
TI  - Accurate prediction of the relative potencies of members of a series of kinase
      inhibitors using molecular docking and MM-GBSA scoring.
AB  - The ability of molecular docking, using the program Glide and an MM-GBSA
      postdocking scoring protocol, to correctly rank a number of congeneric kinase
      inhibitors was assessed. The approach was successful for the cases considered and
      suggests that this may be useful for the design of inhibitors in the lead
      optimization phase of drug discovery.

PMID- 16884291
TI  - Highly potent and selective histone deacetylase 6 inhibitors designed based on a
      small-molecular substrate.
AB  - To find novel histone deacetylase 6 (HDAC6)-selective inhibitors and clarify the
      structural requirements for HDAC6-selective inhibition, we prepared thiolate
      analogues designed based on the structure of an HDAC6-selective substrate and
      evaluated the histone/alpha-tubulin acetylation selectivity by Western blot
      analysis. Aliphatic compounds 17b-20b selectively caused alpha-tubulin
      acetylation over histone H4 acetylation. In enzyme assays using HDAC1, HDAC4, and
      HDAC6, compounds 17a-19a exhibited HDAC6-selective inhibition over HDAC1 and
      HDAC4.

PMID- 16884292
TI  - Potential lead for an Alzheimer drug: a peptide that blocks intermolecular
      interaction and amyloid beta protein-induced cytotoxicity.
AB  - A peptide chAbeta30-16 (15-mer; CTFVRTHIFCKEHQF) was designed to bind to a region
      encompassing the entire polymerization-related (16KLVFF20) and part of the
      polymerization and toxicity-related (25GSNKGAIIGLM35) regions of amyloid beta
      protein, Abeta1-42 by a hydropathic complementary approach. This peptide
      efficiently binds to Abeta and blocks intermolecular interaction and the
      formation of Abeta aggregates. In addition, the peptide neutralizes the cell
      toxicity of Abeta fibrils. The chAbeta30-16 peptide or its derivatives may be a
      starting point for the future development of drugs that prevent the neurotoxicity
      and deposition of Abeta in the brain of Alzheimer's disease.

PMID- 16884294
TI  - Galactosyl derivatives of L-arginine and D-arginine: synthesis, stability, cell
      permeation, and nitric oxide production in pituitary GH3 cells.
AB  - Nitric oxide (NO) is critical for the normal physiological regulation of the
      nervous system and other tissues. L-Arginine, but not D-arginine, is the natural
      substrate for nitric oxide synthase (NOS), for it is enzymatically converted to
      NO and L-citrulline. However, recent evidence suggests that D-arginine can also
      produce NO and NO-derivatives via a different pathway. The aim of the present
      paper was to raise NO levels in the cells by increasing the cell permeation of
      its precursors. To this aim, two galactosyl prodrugs, L-arginine-D-galactos-6'-yl
      ester (L-ArgGal) and D-arginine-D-galactos-6'-yl ester (D-ArgGal) were
      synthesized. Remarkably, using the HPLC-ESI/MS technique, we found that L-ArgGal
      and D-ArgGal prodrugs both increased the concentration levels of L- and D
      arginine and their derivatives in pituitary GH3 cells. Furthermore, we found that
      D-ArgGal (1) penetrated cell membranes more rapidly than its precursor D
      arginine, (2) released arginine more slowly and in greater amounts than L-ArgGal,
      and (3) produced much higher levels of DAF-2 monitored NO and nitrite than did L
      ArgGal under the same experimental conditions. In conclusion, these results
      indicate that an increase in the cell permeation of L- and D-arginine by L-ArgGal
      and D-ArgGal can lead to an increase in NO levels.

PMID- 16884295
TI  - Structure-activity relationships of [2',5'-bis-O-(tert-butyldimethylsilyl)-beta-D
      ribofuranosyl]- 3'-spiro-5' '-(4' '-amino-1' ',2' '-oxathiole-2' ',2' '
      dioxide)thymine derivatives as inhibitors of HIV-1 reverse transcriptase
      dimerization.
AB  - The polymerase activity of HIV-1 reverse transcriptase (RT) is entirely dependent
      on the heterodimeric structure of the enzyme. Accordingly, RT dimerization
      represents a target for the development of a new therapeutic class of HIV
      inhibitors. We previously demonstrated that the N-3-ethyl derivative of 2',5'-bis
      O-(tert-butyldimethylsilyl)-beta-D-ribofuranosyl]-3'-spiro-5' '-(4' '-amino-1'
      ',2' '-oxathiole-2' ',2' '-dioxide)thymine (TSAO-T) destabilizes the inter
      subunit interactions of HIV-1 RT [Sluis-Cremer, N.; Dmietrinko, G. I.; Balzarini,
      J.; Camarasa, M.-J.; Parniak, M. A. Biochemistry 2000, 39, 1427-1433]. In the
      current study, we evaluated the ability of 64 TSAO-T derivatives to inhibit RT
      dimerization using a novel screening assay. Five derivatives were identified with
      improved activity compared to TSAO-T. Four of these harbored hydrophilic or
      aromatic substituents at the N3 position. Furthermore, a good correlation between
      the ability of the TSAO-T derivatives to inhibit RT dimerization and the enzyme's
      polymerase activity was also observed. This study provides an important framework
      for the rational design of more potent inhibitors of RT dimerization.

PMID- 16884293
TI  - Synthesis of trifluoromethylaryl diazirine and benzophenone derivatives of
      etomidate that are potent general anesthetics and effective photolabels for
      probing sites on ligand-gated ion channels.
AB  - To locate the binding sites of general anesthetics on ligand-gated ion channels,
      two derivatives of the intravenous general anesthetic etomidate (2-ethyl 1
      (phenylethyl)-1H-imidazole-5-carboxylate), in which the 2-ethyl group has been
      replaced by photoactivable groups based on either aryl diazirine or benzophenone
      chemistry, have been synthesized and characterized pharmacologically. TDBzl
      etomidate (4-[3-(trifluoromethyl)-3H-diazirin-3-yl]benzyl 1-(1-phenylethyl)-1H
      imidazole-5-carboxylate) and BzBzl-etomidate (4-benzoylbenzyl-1-(1-phenylethyl)
      1H-imidazole-5-carboxylate are both potent general anesthetics with half
      effective anesthetic concentrations of 700 and 220 nM, respectively. Both agents
      resembled etomidate in enhancing currents elicited by low concentrations of GABA
      on heterologously expressed GABAA receptors and in shifting the GABA
      concentration-response curve to lower concentrations. They also allosterically
      enhanced the binding of flunitrazepam to mammalian brain GABAA receptors. Both
      agents were also effective and selective photolabels, photoincorporating into
      some, but not all, subunits of the Torpedo nicotinic acetylcholine receptor to a
      degree that was allosterically regulated by an agonist or a noncompetitive
      inhibitor. Thus, they have the necessary pharmacological and photochemical
      properties to be useful in identifying the site of etomidate-induced anesthesia.

PMID- 16884296
TI  - Novel antibacterial class: a series of tetracyclic derivatives.
AB  - We describe the synthesis and antibacterial activity of a series of tetracyclic
      naphthyridones. The members of this series act primarily via inhibition of
      bacterial translation and belong to the class of novel ribosome inhibitors
      (NRIs). In this paper we explore the structure-activity relationships (SAR) of
      these compounds to measure their ability both to inhibit bacterial translation
      and also to inhibit the growth of bacterial cells in culture. The most active of
      these compounds inhibit Streptococcus pneumoniae translation at concentrations of
      <5 microM and have minimum inhibitory concentrations (MICs) of <8 microg/mL
      against clinically relevant strains of bacteria.

PMID- 16884297
TI  - Inhibition of kinesin motor proteins by adociasulfate-2.
AB  - Kinesin motor proteins are involved in cell division and intracellular transport
      of vesicles and organelles, and as such, they play a role in neurological
      disease, cancer, and developmental disorders. Inhibitors of kinesin would be
      valuable as probes of cell physiology and as potential therapeutics.
      Adociasulfate-2 (AS-2) is the only known natural product inhibitor of kinesins,
      but its mechanism of action is unknown. We utilized kinetic studies, dynamic
      light scattering, and transmission electron microscopy to investigate the
      inhibitory action of AS-2. Our data suggest that AS-2 is not a classical 1:1
      inhibitor. Instead, a rodlike aggregate that mimics microtubules is complexed
      with kinesin and inhibits its ATPase activity. An intriguing implication of this
      hypothesis is that aggregates of a chiral natural product can have interesting
      and biologically relevant properties. This mode of action might represent one way
      in which a small molecule can disrupt a protein-protein interaction.

PMID- 16884298
TI  - Chromatographic estimation of drug disposition properties by means of immobilized
      artificial membranes (IAM) and C18 columns.
AB  - Chromatographic retention measurement in immobilized artificial membranes (IAMs)
      is considered a fast and reliable method to predict biological properties (drug
      distribution) because of the IAM structure, which consists of phospholipid
      analogues bonded covalently to silica particles. A new parameter (d) is proposed
      to estimate the similarity between IAM columns, conventional HPLC columns, and
      drug distribution systems, and thus the performance of chromatographic systems to
      predict drug distribution. An IAM.PC.DD2 column has been used for this study,
      together with two XTerra columns (MSC18 and RP18), at several acetonitrile-water
      mobile phases. According to the d parameter, good correlations should be obtained
      between chromatographic systems (both IAM and C18) and octanol-water partition
      coefficient (log P), and thus both types of columns could be used to obtain log P
      values. The IAM.PC.DD2 system shows a close similarity to human skin partition,
      tadpole narcosis, and blood-brain permeability processes, showing that it can be
      useful as a model for these biological processes. Controversially, it is shown
      that human skin permeation is more similar to C18 partition than to IAM
      partition. Other biological processes such as blood-brain distribution and tissue
      blood partition show a poor similarity to IAM and C18 systems, demonstrating that
      estimation of these drug distribution processes by chromatographic measurements
      may not be adequate.

PMID- 16884299
TI  - Brunsvicamides A-C: sponge-related cyanobacterial peptides with Mycobacterium
      tuberculosis protein tyrosine phosphatase inhibitory activity.
AB  - The cyanobacterium Tychonema sp. produces the new cyclic hexapeptides
      brunsvicamide A-C (1-3). Brunsvicamide B (2) and C (3) selectively inhibit the
      Mycobacterium tuberculosis protein tyrosine phosphatase B (MptpB), a potential
      drug target for tuberculosis therapy for which no inhibitors are known to date.
      Brunsvicamide C contains an N-methylated N'-formylkynurenine moiety, a unique
      structural motif in cyclic peptides. The new peptides are related to the sponge
      derived mozamides, supporting the suggestion that secondary metabolites of
      certain marine invertebrates are produced by associated microorganisms. Thus,
      microorganisms phylogenetically related to symbionts of marine invertebrates can
      be judged as a means to supply "marine-like" compounds for drug development.

PMID- 16884300
TI  - Synthesis and antifungal activity of a novel series of alkyldimethylamine
      cyanoboranes and their derivatives.
AB  - A series of new amine cyanoborane derivatives were synthesized and exhibited
      antifungal activity. A long alkyl chain attached to the nitrogen of the amine
      cyanoboranes and carboxyboranes enhances antifungal activity. An enhanced
      activity was also obtained upon the halogenation of the amine cyanoboranes as
      well as in the presence of C=C double bond at the end of the N-alkyl group. The
      lead compounds were dimethylundecylamine cyanoborane (C11H23N(CH3)2BH2CN), 9, and
      its dibromo derivative dimethylundecylamine dibromocyanoborane
      (C11H23N(CH3)2BBr2CN), 11. The MIC values for the lead compounds against the most
      important human pathogenic fungi ranged from 16.25 to 32.5 micromol/L and from
      10.05 to 79 micromol/L, respectively. Both compounds were found to be relatively
      safe in intravenous injections to mice, (MTD = 121.9 and 73.1 micromol/kg,
      respectively) and active against strains that are resistant to fluconazole (a
      conventional antifungal medicine). These data indicate their potential to become
      antifungal agents.

PMID- 16884301
TI  - Structural determinants for the membrane interaction of novel bioactive
      undecapeptides derived from gaegurin 5.
AB  - Gaegurin 5 is a 24-residue, membrane-active antimicrobial peptide isolated from
      the skin of an Asian frog, Rana rugosa. We recently reported the antimicrobial
      activities of two novel undecapeptides derived from an inactive N-terminal
      fragment (residues 1-11) of gaegurin 5 (Won, et al. J. Biol. Chem. 2004, 279,
      14784-14791). In the present work, the anticancer activities of the two
      antimicrobial undecapeptide analogues were additionally identified. The
      relationships between their structural properties and biological activities were
      assessed by characterizing the fundamental structural determinant for the basic
      membrane interaction. The circular dichroism and nuclear magnetic resonance
      results revealed that in a membrane-mimetic environment, the active peptides
      adopt a more stabilized helical conformation than that of the inactive fragment,
      and this conformation conferred an overall amphipathicity to the active peptides.
      Therefore, the most decisive factor responsible for the activity and selectivity
      could be the intramolecular amphipathic cooperativity, rather than the
      amphipathicity itself. Especially, the tryptophan residue of the active peptides
      seems to play a crucial role at the critical amphipathic interface that promotes
      and balances the amphipathic cooperativity by stabilizing both the hydrophilic
      and hydrophobic interactions with the membrane. Altogether, the present results
      suggest that the two novel undecapeptides are worthy of therapeutic development
      as new antibiotic and anticancer agents and provide structural information about
      their action mechanism.

PMID- 16884302
TI  - 4-Phenylpyrrolo[3,4-c]carbazole-1,3(2H,6H)-dione inhibitors of the checkpoint
      kinase Wee1. Structure-activity relationships for chromophore modification and
      phenyl ring substitution.
AB  - High-throughput screening has identified a novel class of inhibitors of the
      checkpoint kinase Wee1, which have potential for use in cancer chemotherapy.
      These inhibitors are based on a 4-phenylpyrrolo[3,4-c]carbazole-1,3(2H,6H)-dione
      template and have been shown by X-ray crystallography to bind at the ATP site of
      the enzyme. An extensive study of the effects of substitution around this
      template has been carried out, which has identified substituents which lead to
      improvements in potency and selectivity for Wee1. While retention of the
      maleimide ring and pendant 4-phenyl group is necessary for potency, replacement
      of the carbazole nitrogen by oxygen is well tolerated and results in improved
      Wee1 selectivity against the related checkpoint kinase Chk1. Wee1 potency and
      selectivity are also enhanced by the incorporation of lipophilic functionality at
      the 2'-position of the 4-phenyl ring, and Wee1 selectivity against Chk1 is
      favored by C3-C5 alkyl substitution of the carbazole nitrogen. These studies
      provide a basis for the design of active analogues of the pyrrolocarbazole lead
      with improved physical properties.

PMID- 16884303
TI  - Structural insights into monoamine oxidase inhibitory potency and selectivity of
      7-substituted coumarins from ligand- and target-based approaches.
AB  - A new series of 3-, 4-, 7-polysubstituted coumarins have been designed and
      evaluated for their monoamine oxidase A and monoamine oxidase B (MAO-A and MAO-B)
      inhibitory potency. Substituents at position 7 consisted of a bridge of different
      physicochemical nature linking a phenyl ring to the coumarin scaffold. Structure
      affinity and structure-selectivity relationships, derived through CoMFA-GOLPE and
      docking studies, revealed the key physicochemical interactions responsible for
      the observed MAO-B and MAO-A inhibitory potency and suggested the main structural
      determinants for high selectivity toward one of the two enzymatic isoforms. The
      predictive power of our models was proved with the design of a new inhibitor
      demonstrating an outstanding MAO-B affinity (pIC50 = 8.29) and the highest MAO-B
      selectivity (DeltapIC50 = 3.39) within the entire series of ligands examined
      herein.

PMID- 16884304
TI  - In vitro and in vivo magnetic resonance detection of tumor cells by targeting
      glutamine transporters with Gd-based probes.
AB  - The glutamine transporting system is up-regulated in tumor cells because cell
      proliferation requires the uptake of large quantities of glutamine. It has been
      found that the paramagnetic magnetic resonance imaging (MRI) reporter Gd-DOTAMA
      C6-Gln, where the glutamine residue is covalently bound to the Gd chelate through
      a C6 spacer, accumulates in tumor cells both "in vitro" and "in vivo"
      experiments. The observation that the relaxivity of cellular pellets does not
      increase with the increase in the amounts of entrapped Gd chelate is taken as an
      indication that the internalization has occurred through receptor mediated
      endocytosis. The iv administration of Gd-DOTAMA-C6-Gln allowed the MRI
      visualization of tumor masses in A/J mice grafted with the murine neuroblastoma
      cell line Neuro-2a and in Her-2/neu transgenic mice developing multiple mammary
      carcinoma, respectively.

PMID- 16884305
TI  - Design of inhibitors of orotidine monophosphate decarboxylase using bioisosteric
      replacement and determination of inhibition kinetics.
AB  - Inhibitors of orotidine monophosphate decarboxylase (ODCase) have applications in
      RNA viral, parasitic, and other infectious diseases. ODCase catalyzes the
      decarboxylation of orotidine monophosphate (OMP), producing uridine monophosphate
      (UMP). Novel inhibitors 6-amino-UMP and 6-cyano-UMP were designed on the basis of
      the substructure volumes in the substrate OMP and in an inhibitor of ODCase,
      barbituric acid monophosphate, BMP. A new enzyme assay method using isothermal
      titration calorimetry (ITC) was developed to investigate the inhibition kinetics
      of ODCase. The reaction rates were measured by monitoring the heat generated
      during the decarboxylation reaction of orotidine monophosphate. Kinetic
      parameters (k(cat) = 21 s(-1) and KM = 5 microM) and the molar enthalpy
      (DeltaH(app) = 5 kcal/mol) were determined for the decarboxylation of the
      substrate by ODCase. Competitive inhibition of the enzyme was observed and the
      inhibition constants (Ki) were determined to be 12.4 microM and 29 microM for 6
      aza-UMP and 6-cyano-UMP, respectively. 6-Amino-UMP was found to be among the
      potent inhibitors of ODCase, having an inhibition constant of 840 nM. We reveal
      here the first inhibitors of ODCase designed by the principles of bioisosterism
      and a novel method of using isothermal calorimetry for enzyme inhibition studies.

PMID- 16884306
TI  - Antimycobacterial agents. Novel diarylpyrrole derivatives of BM212 endowed with
      high activity toward Mycobacterium tuberculosis and low cytotoxicity.
AB  - On the basis of suggestions derived either from a pharmacophoric model for
      antitubercular agents or from a structure-activity relationship analysis of many
      pyrroles previously described by us, we report here the design and synthesis of
      new analogues of 1,5-(4-chlorophenyl)-2-methyl-3-(4-methylpiperazin-1-yl)methyl
      1H-pyrrole (BM212). Various substituents with different substitution patterns
      were added to both positions 1 and 5 of the pyrrole nucleus to evaluate their
      influence on the activity toward Mycobacterium tuberculosis (MTB) and atypical
      mycobacteria. Biological data showed that, although some nontuberculosis
      mycobacterial strains were found to be sensitive, MIC values were higher than
      those found toward MTB. The best compound (1-(4-fluorophenyl)-2-methyl-3
      (thiomorpholin-4-yl)methyl-5-(4-methylphenyl)-1H-pyrrole, 5) possessed a MIC of
      0.4 microg/mL (better than BM212 and streptomycin) and a very high protection
      index (160), better than BM212, isoniazid, and streptomycin (6, 128, and 128,
      respectively). Finally, molecular modeling studies were performed to rationalize
      the activity of the new compounds in terms of both superposition onto a
      pharmacophoric model for antitubercular compounds and their hydrophobic
      character.

PMID- 16884307
TI  - Structural and quantum chemical studies of 8-aryl-sulfanyl adenine class Hsp90
      inhibitors.
AB  - Hsp90 chaperones play a critical role in modulating the activity of many cell
      signaling proteins and are an attractive target for anti-cancer therapeutics. We
      report here the structures of the water soluble 8-aryl-sulfanyl adenine class
      Hsp90 inhibitors, 1 (PU-H71) and 2 (PU-H64), in complex with the N-terminal
      domain of human Hsp90alpha. The conformation of 1 when bound to Hsp90 differs
      from previously reported 8-aryl adenine Hsp90 inhibitors including 3 (PU24FCl).
      While the binding mode for 3 places the 2'-halide of the 8-aryl group on top of
      the adenine ring, for 1 and 2, we show that the 2'-halide is rotated
      approximately 180 degrees away. This difference explains the opposing trends in
      Hsp90 inhibitory activity for the 2'-halo derivatives of the 3',4',5'-trimethoxy
      series where Cl > Br > I compared to the 4',5'-methylenedioxy series where I > Br
      > Cl. We also present quantum chemical calculations of 2 and its analogues that
      illuminate their basis for Hsp90 inhibition. The calculated conformation of 2
      agreed well with the crystallographically observed conformations of 1 and 2. The
      predictive nature of the calculations has allowed the exploration of additional
      derivatives based on the 8-aryl adenine scaffold.

PMID- 16884308
TI  - The physicochemical challenges of designing multiple ligands.
AB  - Compounds designed to bind more than one target can provide a therapeutic benefit
      relative to highly target-selective ligands. The physicochemical properties of
      designed multiple ligands were found to be less druglike than those for
      preclinical compounds in general. These properties are controlled by the
      superfamily to which the targets belong and the lead discovery strategy that was
      followed. The properties for peptide G-protein-coupled receptor (GPCR) ligands
      were the least favorable for oral delivery, whereas transporter, monoamine GPCR,
      and oxidase ligands were the most druglike. The lead discovery strategy,
      framework combination or screening, exerts a profound influence on the property
      values. Combining the frameworks from two selective ligands often results in
      large, complex dual ligands, but druglike ligands can be achieved if the degree
      of framework overlap is maximized and the size of the selective ligands
      minimized. For some target combinations, a screening approach may provide a route
      to smaller, less complex leads.

PMID- 16884309
TI  - Synthesis, crystal structure, structure-activity relationships, and antiviral
      activity of a potent SARS coronavirus 3CL protease inhibitor.
AB  - A potent SARS coronavirus (CoV) 3CL protease inhibitor (TG-0205221, Ki = 53 nM)
      has been developed. TG-0205221 showed remarkable activity against SARS CoV and
      human coronavirus (HCoV) 229E replications by reducing the viral titer by 4.7 log
      (at 5 microM) for SARS CoV and 5.2 log (at 1.25 microM) for HCoV 229E. The
      crystal structure of TG-0205221 (resolution = 1.93 A) has revealed a unique
      binding mode comprising a covalent bond, hydrogen bonds, and numerous hydrophobic
      interactions. Structural comparisons between TG-0205221 and a natural peptide
      substrate were also discussed. This information may be applied toward the design
      of other 3CL protease inhibitors.

PMID- 16884310
TI  - Novel 2-aminopyrimidine carbamates as potent and orally active inhibitors of Lck:
      synthesis, SAR, and in vivo antiinflammatory activity.
AB  - The lymphocyte-specific kinase (Lck) is a cytoplasmic tyrosine kinase of the Src
      family expressed in T cells and NK cells. Genetic evidence in both mice and
      humans demonstrates that Lck kinase activity is critical for signaling mediated
      by the T cell receptor (TCR), which leads to normal T cell development and
      activation. A small molecule inhibitor of Lck is expected to be useful in the
      treatment of T cell-mediated autoimmune and inflammatory disorders and/or organ
      transplant rejection. In this paper, we describe the synthesis, structure
      activity relationships, and pharmacological characterization of 2-aminopyrimidine
      carbamates, a new class of compounds with potent and selective inhibition of Lck.
      The most promising compound of this series, 2,6-dimethylphenyl 2-((3,5
      bis(methyloxy)-4-((3-(4-methyl-1-piperazinyl)propyl)oxy)phenyl)amino)-4
      pyrimidinyl(2,4-bis(methyloxy)phenyl)carbamate (43) exhibits good activity when
      evaluated in in vitro assays and in an in vivo model of T cell activation.

PMID- 16884311
TI  - Probing hot spots at protein-ligand binding sites: a fragment-based approach
      using biophysical methods.
AB  - Mapping interactions at protein-ligand binding sites is an important aspect of
      understanding many biological reactions and a key part of drug design. In this
      paper, we have used a fragment-based approach to probe "hot spots" at the
      cofactor-binding site of a model dehydrogenase, Escherichia coli ketopantoate
      reductase. Our strategy involved the breaking down of NADPH (Kd = 300 nM) into
      smaller fragments and the biophysical characterization of their binding using
      WaterLOGSY NMR spectroscopy, isothermal titration calorimetry (ITC), and
      inhibition studies. The weak binding affinities of fragments were measured by
      direct ITC titrations under low c value conditions. The 2'-phosphate and the
      reduced nicotinamide groups were found to contribute a large part of the binding
      energy. A combination of ITC and site-directed mutagenesis enabled us to locate
      the fragments at separate hot spots on opposite ends of the cofactor-binding
      site. This study has identified structural determinants for cofactor recognition
      that represent a blueprint for future inhibitor design.

PMID- 16884313
TI  - NMR structure of a potent small molecule inhibitor bound to human keratinocyte
      fatty acid-binding protein.
AB  - The NMR structure is presented for compound 1 (BMS-480404) (Ki = 33 (+/-2) nM)
      bound to keratinocyte fatty acid-binding protein. This article describes
      interactions between a high affinity drug-like compound and a member of the fatty
      acid-binding protein family. A benzyl group ortho to the mandelic acid in 1
      occupies an area of the protein that fatty acids do not normally contact. Similar
      to that in the kFABP-palmitic acid structure, the acid moiety in 1 is proximal to
      R129 and Y131. Computational modeling indicates that the acid moiety in 1
      interacts indirectly via a modeled water molecule to R109.

PMID- 16884312
TI  - Synthesis of anthranylaldoxime derivatives as estrogen receptor ligands and
      computational prediction of binding modes.
AB  - N-Me-anthranylaldoximes possess a hydrogen-bonded pseudocyclic A' ring in place
      of the typical phenolic A-ring that is characteristic of most estrogen receptor
      (ER) ligands. We have investigated the role played by substituents introduced
      into either one or both of the peripheral 3- and 4-phenyl rings in modulating ER
      binding affinity. An efficient synthetic strategy was employed for the
      preparation of differentially substituted 3- and 4-aryl derivatives that involved
      exploiting the different reactivity of bromo- versus chloro-aryl groups in
      palladium-catalyzed cross-couplings. The binding data showed that ERalpha
      affinity could be improved by a single p-OH group in the 4-phenyl ring, whereas
      the same substitution on the 3-phenyl ring caused a dramatic reduction of ERbeta
      affinity. The most ERalpha-selective compound was the one with two p-OH groups on
      both phenyl substituents. To rationalize these results, ligand docking followed
      by molecular mechanics Poisson-Boltzmann/surface area (MM-PBSA) studies were
      carried out. These analyses suggested a molecular basis for the interaction of
      these compounds with the ERs and enabled the development of models able to
      predict the mode of ligand binding.

PMID- 16884314
TI  - Novel methylenephosphophosphonate analogues of mycophenolic adenine dinucleotide.
      Inhibition of inosine monophosphate dehydrogenase.
AB  - Novel methylenephosphophosphonate analogues of mycophenolic adenine dinucleotide
      (MAD) have been prepared as potential inhibitors of IMP dehydrogenase. A coupling
      of the mycophenolic (hydroxymethyl)phosphonate 6 with the phosphitylated
      adenosine analogue 11 followed by oxidation and deprotection afforded the
      phosphophosphonate 8. A similar coupling between adenosine
      (hydroxymethyl)phosphonate 10 and phosphitylated mycophenolic alcohol 5 gave the
      corresponding phosphophosphonate 13. Both 8 and 13 (Ki = 20-87 nM) were found to
      be the most potent cofactor type inhibitors of IMP dehydrogenase.

PMID- 16884317
TI  - Chronopharmacokinetics of ciclosporin and tacrolimus.
AB  - The correct use of immunosuppressive drugs has a considerable influence on the
      prognosis of patients with organ transplants. The appropriate utilisation of the
      drugs involves the administration of an adequate dosage to reach the blood
      concentrations that will suppress the alloimmune response, while avoiding
      secondary toxicities. However, transplanted patients exhibit heterogeneous
      immunological responses and high inter- and intraindividual pharmacokinetic
      variabilities. One cause of these variabilities that is rarely considered is
      circadian rhythms. In vitro and in vivo experiments have clearly demonstrated
      that all organisms are highly organised according to an internal biological clock
      that influences various physiological functions. Considering that the absorption,
      distribution, metabolism and elimination of drugs is influenced by the
      physiological functions of the body, it is not surprising that the
      pharmacokinetic, and consequently the pharmacodynamic, profiles of drugs can be
      influenced by circadian rhythms. Ciclosporin, a mainstay immunosuppressive drug
      used following organ transplantation, displays minimum blood concentration
      (C(min)), maximum blood concentration (C(max)) and area under the blood
      concentration-time curve (AUC) in the morning that are generally higher than the
      corresponding parameters in the evening. These observations are supported by the
      ciclosporin total body clearance and elimination half-life in the morning, which
      are, on average, higher and shorter, respectively, than those in the evening. In
      addition, the disposition of tacrolimus is determined by the time of
      administration. The tacrolimus C(max) and AUC after the morning dose are
      significantly higher than those after the evening dose. Finally, the results
      reported in this review suggest considering more carefully the
      chronopharmacokinetics of tacrolimus and ciclosporin in order to obtain better
      results with fewer adverse effects. Significantly, the morning appears to be the
      best time for therapeutic monitoring using the C(min), C(max), concentration at 2
      hours after dosing and AUC to modify dosages of tacrolimus and ciclosporin. Less
      certain are any conclusions about whether, in order to obtain better
      immunosuppressive control, higher doses must be administered when these drugs are
      given in the evening to compensate for the higher levels of interleukin-2.

PMID- 16884318
TI  - Lack of pharmacokinetic interaction for ISIS 113715, a 2'-0-methoxyethyl modified
      antisense oligonucleotide targeting protein tyrosine phosphatase 1B messenger
      RNA, with oral antidiabetic compounds metformin, glipizide or rosiglitazone.
AB  - BACKGROUND: ISIS 113715 is a 20-mer phosphorothioate antisense oligonucleotide
      (ASO) that is complementary to the protein tyrosine phosphatase 1B (PTP-1B)
      messenger RNA and subsequently reduces translation of the PTP-1B protein, a
      negative regulator of insulin receptor. ISIS 113715 is currently being studied in
      early phase II clinical studies to determine its ability to improve or restore
      insulin receptor sensitivity in patients with type 2 diabetes mellitus. Future
      work will investigate the combination of ISIS 113715 with antidiabetic compounds.
      METHODS: In vitro ultrafiltration human plasma protein binding displacement
      studies and a phase I clinical study were used to characterise the potential for
      pharmacokinetic interaction of ISIS 113715 and three marketed oral antidiabetic
      agents. ISIS 113715 was co-incubated with glipizide and rosiglitazone in whole
      human plasma and tested for increased free drug concentrations. In a phase I
      clinical study, 23 healthy volunteers received a single oral dose of an
      antidiabetic compound (either metformin, glipizide or rosiglitazone) both alone
      and together with subcutaneous ISIS 113715 200 mg in a sequential crossover
      design. A comparative pharmacokinetic analysis was performed to determine if
      there were any effects that resulted from coadministration of ISIS 113715 with
      these antidiabetic compounds. RESULTS: In vitro human plasma protein binding
      displacement studies showed only minor effects on rosiglitazone and no effect on
      glipizide when co-incubated with ISIS 113715. The results of the phase I clinical
      study further indicate that there were no measurable changes in glipizide (5 mg),
      metformin (500 mg) or rosiglitazone (2 mg) exposure parameters, maximum plasma
      concentration and the area under the concentration-time curve, or pharmacokinetic
      parameter, elimination half-life when coadministered with ISIS 113715.
      Furthermore, there was no effect of ISIS 113715, administered in combination with
      metformin, on the urinary excretion of metformin. Conversely, there were no
      observed alterations in ISIS 113715 pharmacokinetics when administered in
      combination with any of the oral antidiabetic compounds. CONCLUSION: These data
      provide evidence that ISIS 113715 exhibits no clinically relevant pharmacokinetic
      interactions on the disposition and clearance of the oral antidiabetic drugs. The
      results of these studies support further study of ISIS 113715 in combination with
      antidiabetic compounds.

PMID- 16884319
TI  - Population pharmacokinetics of melagatran, the active form of the oral direct
      thrombin inhibitor ximelagatran, in atrial fibrillation patients receiving long
      term anticoagulation therapy.
AB  - BACKGROUND: Ximelagatran is an oral direct thrombin inhibitor for the prevention
      of thromboembolic disease. After oral administration, ximelagatran is rapidly
      absorbed and bioconverted to its active form, melagatran. OBJECTIVE: To
      characterise the pharmacokinetics of melagatran in patients with nonvalvular
      atrial fibrillation (NVAF) receiving long-term treatment for prevention of stroke
      and systemic embolic events. METHODS: A population pharmacokinetic model was
      developed based on data from three phase II studies (1177 plasma concentration
      observations in 167 patients, treated for up to 18 months) and confirmed by
      including data from two phase III studies (8702 plasma concentration observations
      in 3188 patients, treated for up to 24 months). The impact of individualised
      dosing on pharmacokinetic variability was evaluated by simulations of melagatran
      concentrations based on the pharmacokinetic model. RESULTS: Melagatran
      pharmacokinetics were consistent across the studied doses and duration of
      treatment, and were described by a one-compartment model with first-order
      absorption and elimination. Clearance of melagatran was correlated to creatinine
      clearance, which was the most important predictor of melagatran exposure
      (explained 54% of interpatient variance in clearance). Total variability
      (coefficient of variation) in exposure was 45%; intraindividual variability in
      exposure was 23%. Concomitant medication with the most common long-term used
      drugs in the study population had no relevant influence on melagatran
      pharmacokinetics. Simulations suggested that dose adjustment based on renal
      function or trough plasma concentration had a minor effect on overall
      pharmacokinetic variability and the number of patients with high melagatran
      exposure. CONCLUSION: The pharmacokinetics of melagatran in NVAF patients were
      predictable, and consistent with results from previously studied patient
      populations. Dose individualisation was predicted to have a low impact on
      pharmacokinetic variability, supporting the use of a fixed-dose regimen of
      ximelagatran for long-term anticoagulant therapy in the majority of NVAF
      patients.

PMID- 16884320
TI  - Pharmacokinetics, pharmacodynamics and safety of febuxostat, a non-purine
      selective inhibitor of xanthine oxidase, in a dose escalation study in healthy
      subjects.
AB  - BACKGROUND: Febuxostat is a novel non-purine selective inhibitor of xanthine
      oxidase currently being developed for the management of hyperuricemia in patients
      with gout. OBJECTIVE: To investigate the pharmacokinetics, pharmacodynamics and
      safety of febuxostat over a range of oral doses in healthy subjects. METHODS: In
      a phase I, dose-escalation study, febuxostat was studied in dose groups (10, 20,
      30, 40, 50, 70, 90, 120, 160, 180 and 240 mg) of 12 subjects each (10 febuxostat
      plus 2 placebo). In all groups, subjects were confined for 17 days and were
      administered febuxostat once daily on day 1, and days 3-14. During the course of
      the study, blood and urine samples were collected to assess the pharmacokinetics
      of febuxostat and its metabolites, and its pharmacodynamic effects on uric acid,
      xanthine and hypoxanthine concentrations after both single and multiple dose
      administration. Safety measurements were also obtained during the study. RESULTS:
      Orally administered febuxostat was rapidly absorbed with a median time to reach
      maximum plasma concentration following drug administration of 0.5-1.3 hours. The
      pharmacokinetics of febuxostat were not time dependent (day 14 vs day 1) and
      remained linear within the 10-120 mg dose range, with a mean apparent total
      clearance of 10-12 L/h and an apparent volume of distribution at steady state of
      33-64 L. The harmonic mean elimination half-life of febuxostat ranged from 1.3 to
      15.8 hours. The increase in the area under the plasma concentration-time curve of
      febuxostat at doses >120 mg appeared to be greater than dose proportional, while
      the febuxostat maximum plasma drug concentration was dose proportional across all
      the doses studied. Based on the urinary data, febuxostat appeared to be
      metabolised via glucuronidation (22-44% of the dose) and oxidation (2-8%) with
      only 1-6% of the dose being excreted unchanged via the kidneys. Febuxostat
      resulted in significant decreases in serum and urinary uric acid concentrations
      and increases in serum and urinary xanthine concentrations. The percentage
      decrease in serum uric acid concentrations ranged from 27% to 76% (net change:
      1.34-3.88 mg/dL) for all doses and was dose linear for the 10-120 mg/day dosage
      range. The majority of adverse events were mild-to-moderate in intensity.
      CONCLUSION: Febuxostat was well tolerated at once-daily doses of 10-240 mg. There
      appeared to be a linear pharmacokinetic and dose-response (percentage decrease in
      serum uric acid) relationship for febuxostat dosages within the 10-120 mg range.
      Febuxostat was extensively metabolised and renal function did not seem to play an
      important role in its elimination from the body.

PMID- 16884321
TI  - Comparison of equivalent doses of fentanyl buccal tablets and arteriovenous
      differences in fentanyl pharmacokinetics.
AB  - BACKGROUND: The fentanyl buccal tablet (FBT) is designed to enhance the rate and
      extent of fentanyl absorption through the buccal mucosa. AIM: To evaluate the
      bioequivalence of microg-equivalent doses of FBT administered as single and
      multiple tablets and assess differences in the arterial and venous
      pharmacokinetics of FBT in healthy volunteers. METHODS: Twenty-seven healthy
      adults, aged 19-45 years, participated in the randomised, open-label, three
      period, crossover study. In the first two periods, FBT was administered as four
      100 microg tablets simultaneously or one FBT 400 microg to assess bioequivalence.
      Venous blood samples were obtained over a 72-hour period to measure plasma
      fentanyl concentrations. In the third period, arterial and venous blood samples
      were obtained simultaneously from before administration of one FBT 400 microg
      through 4 hours after administration to evaluate the impact of arterial versus
      venous sampling on the pharmacokinetic profile. As subjects were not opioid
      tolerant, naltrexone was administered to block opioid receptor-mediated effects
      of fentanyl. Adverse events were recorded throughout. RESULTS: Maximum plasma
      concentration (C(max)) and area under the plasma concentration-time curve from
      time zero to infinity (AUC(infinity)) on average were approximately 12% and 13%
      higher, respectively, for FBT administered as four 100 microg tablets
      simultaneously compared with one FBT 400 microg. Maximum plasma concentrations in
      the arterial circulation were approximately 60% higher and occurred 15 minutes
      earlier than those measured from the venous circulation. No serious adverse
      events were reported during the study. CONCLUSION: Despite small differences in
      C(max) and AUC(infinity) (on average 12% and 13%, respectively), FBT administered
      as four 100 microg tablets simultaneously compared with one 400 microg tablet did
      not meet the criteria for bioequivalence. An increased surface area exposure with
      four tablets compared with one tablet may account for the slightly higher maximum
      concentrations observed with four 100 microg tablets. A substantially higher
      C(max) was reached earlier in the arterial than in the venous circulation.

PMID- 16884322
TI  - Parametric and nonparametric population methods.

PMID- 16884316
TI  - Antibacterial dosing in intensive care: pharmacokinetics, degree of disease and
      pharmacodynamics of sepsis.
AB  - Treatment of sepsis remains a significant challenge with persisting high
      mortality and morbidity. Early and appropriate antibacterial therapy remains an
      important intervention for such patients. To optimise antibacterial therapy, the
      clinician must possess knowledge of the pharmacokinetic and pharmacodynamic
      properties of commonly used antibacterials and how these parameters may be
      affected by the constellation of pathophysiological changes occurring during
      sepsis. Sepsis, and the treatment thereof, increases renal preload and, via
      capillary permeability, leads to 'third-spacing', both resulting in higher
      antibacterial clearances. Alternatively, sepsis can induce multiple organ
      dysfunction, including renal and/or hepatic dysfunction, causing a decrease in
      antibacterial clearance. Aminoglycosides are concentration-dependent
      antibacterials and they display an increased volume of distribution (V(d)) in
      sepsis, resulting in decreased peak serum concentrations. Reduced clearance from
      renal dysfunction would increase the likelihood of toxicity. Individualised
      dosing using extended interval dosing, which maximises the peak serum drug
      concentration (C(max))/minimum inhibitory concentration ratio is recommended.
      Beta-lactams and carbapenems are time-dependent antibacterials. An increase in
      V(d) and renal clearance will require increased dosing or administration by
      continuous infusion. If renal impairment occurs a corresponding dose reduction
      may be required. Vancomycin displays predominantly time-dependent pharmacodynamic
      properties and probably requires higher than conventionally recommended doses
      because of an increased V(d) and clearance during sepsis without organ
      dysfunction. However, optimal dosing regimens remain unresolved. The poor
      penetration of vancomycin into solid organs may require alternative therapies
      when sepsis involves solid organs (e.g. lung). Ciprofloxacin displays largely
      concentration-dependent kill characteristics, but also exerts some time-dependent
      effects. The V(d) of ciprofloxacin is not altered with fluid shifts or over time,
      and thus no alterations of standard doses are required unless renal dysfunction
      occurs. In order to optimise antibacterial regimens in patients with sepsis, the
      pathophysiological effects of systemic inflammatory response syndrome need
      consideration, in conjunction with knowledge of the different kill
      characteristics of the various antibacterial classes. In conclusion, certain
      antibacterials can have a very high V(d), therefore leading to a low C(max) and
      if a high peak is needed, then this would lead to underdosing. The V(d) of
      certain antibacterials, namely aminoglycosides and vancomycin, changes over time,
      which means dosing may need to be altered over time. Some patients with serum
      creatinine values within the normal range can have very high drug clearances,
      thereby producing low serum drug levels and again leading to underdosing.

PMID- 16884325
TI  - Molecular screening of cancer: the future is here.
AB  - The remarkable growth in our knowledge of the biology of cancer is leading to the
      identification of previously elusive pathways and networks involved in cancer
      causation. The development of technologies has played a pivotal role in
      furthering this understanding and appreciation of the complexity of
      tumorigenesis, and is advancing efforts to fully grasp the biology and exploit
      the knowledge for improvements in cancer detection, prevention, and therapy. The
      future of molecular screening, i.e. detection of risk or cancer via molecular
      determinants, has never been so close to a reality. Molecular assays employed in
      cancer detection and therapy are likely to revolutionize cancer treatment through
      individual-based diagnosis and treatment, i.e. personalized medicine. A number of
      detection techniques, such as the detection of aberrant DNA and RNA, the presence
      of auto-antibodies in serum or plasma, and protein profiling, are already in
      limited use for patient stratification for clinical trials and for predicting
      drug response.

PMID- 16884326
TI  - Digital karyotyping: an update of its applications in cancer.
AB  - DNA copy number alterations, including entire chromosomal changes and small
      interstitial DNA amplifications and deletions, characterize the development of
      cancer. These changes usually affect the expression of target genes and
      subsequently the function of the target proteins. Since the completion of the
      human genome project, the capacity to comprehensively analyze the human cancer
      genome has expanded significantly. Techniques such as digital karyotyping have
      been developed to allow for the detection of DNA copy number alterations in
      cancer at the whole-genome scale. When compared with conventional methods such as
      spectral karyotyping, representational difference analysis, comparative genomic
      hybridization (CGH), or the more recent array CGH; digital karyotyping provides
      an evaluation of copy number of genetic material at higher resolution. Digital
      karyotyping has therefore promised to enhance our understanding of the cancer
      genome. This article provides an overview of digital karyotyping including the
      principle of the technology and its applications in identifying potential
      oncogenes and tumor suppressor genes.

PMID- 16884327
TI  - VHL P25L is not a pathogenic von Hippel-Lindau mutation: a family study.
AB  - BACKGROUND: von Hippel-Lindau (VHL) disease is a hereditary tumor syndrome in
      which affected individuals may develop CNS and retinal hemangioblastomas,
      pheochromocytomas, renal cell carcinoma, and cysts of various organs. The VHL
      gene has been localized to chromosome 3p25-26 and >500 germline mutations have
      been identified. A rare variant of the VHL gene results in the substitution of
      lysine for proline at position 25 (P25L) in the larger of the two VHL proteins.
      This VHL variant has previously been described in a limited number of cases and
      has been strongly suggested to be non-pathogenic, but this has not been proven.
      METHODS: A family with a medical history suggestive of VHL disease was
      investigated using DNA sequence analysis to determine the presence of the P25L
      variant of the VHL protein. RESULTS: Sequence analysis identified the VHL P25L
      variant in 7 of 14 family members, one of whom had a single retinal hemangioma,
      which is in itself insufficient to diagnose VHL disease. The variant was not
      identified in a family member with clear cell renal carcinoma, which is a
      hallmark feature of VHL disease. CONCLUSIONS: On the basis of these results, it
      is concluded that P25L is a benign variant of the VHL protein and individuals
      carrying this variant should not be required to undergo screening for VHL
      manifestations.

PMID- 16884324
TI  - Genetic predisposition and renal allograft failure: implication of non-HLA
      genetic variants.
AB  - Renal allograft rejection or dysfunction often results in graft failure, and
      remains the major obstacle in the success of renal transplantation. Various
      immunological and nonimmunological factors are involved in allograft rejection.
      In addition to human leukocyte antigen loci, several genetically controlled
      molecules have been identified in recent years as playing important roles in the
      process of rejection. Genetic variants in genes encoding different T-helper (Th)
      type 1 and Th2 cytokines, chemokines and their receptors, growth factors,
      molecules of the renin-angiotensin system, enzymes of the homocysteine pathway,
      and proteins acting as substrates of immunosuppressive drugs impact on the
      success of engraftment and highlight the concept of genetic predisposition to
      allograft rejection. This review evaluates specific genetic variants and their
      functional roles in graft failure, with an emphasis on the latest methodologies
      available for genotyping, and appropriate strategies to enable them to become a
      tool of predictive and individualized medicine to ensure better transplant
      outcome.

PMID- 16884328
TI  - Molecular characterization of large deletions in the von Hippel-Lindau (VHL) gene
      by quantitative real-time PCR: the hypothesis of an alu-mediated mechanism
      underlying VHL gene rearrangements.
AB  - INTRODUCTION: Mutations of the von Hippel-Lindau (VHL) gene are responsible for
      VHL disease. This is a familial autosomal-dominant syndrome, predisposing to the
      development of benign and malignant tumors, including CNS and retinal
      hemangioblastomas, pheochromocytomas, and clear cell renal carcinomas. At least
      30% of the disease-causing mutations in the VHL gene involve large alterations.
      Identification of these mutations is not possible using PCR-based mutational
      scanning methods. Quantitative Southern blot analysis has been traditionally
      employed for the detection of complete or partial deletions and more complex
      rearrangements of the gene. METHODS: An alternative quantitative method was
      developed using a combination of quantitative Southern blot analysis and real
      time PCR. With this approach, we studied 24 large VHL gene alterations to
      determine the exact nature of the mutations and to possibly characterize the
      boundaries of the deleted regions. RESULTS: This combined molecular approach
      showed that all the VHL alterations studied were due to deletions, from which the
      position in the gene could be more precisely mapped. One of the samples that was
      completely characterized was found to carry an intragenic 2.2kb deletion with
      both 5' and 3' breakpoints located within Alu-repeat sequences. CONCLUSION: This
      is the first report on the molecular analysis of large VHL alterations. The
      results of our study and the complete characterization of a large deletion lead
      to the hypothesis that an Alu-mediated mechanism may be responsible for the
      common occurrence of large alterations in the VHL gene.

PMID- 16884329
TI  - Detection of Epstein-Barr virus in lower gastrointestinal tract lymphomas: a
      study in Malaysian patients.
AB  - BACKGROUND: Many studies in the literature have shown that Epstein-Barr virus
      (EBV) is associated with several human lymphoid and epithelial malignancies.
      However, the prevalence of EBV in non-Hodgkin lymphoma (NHL) of the lower
      gastrointestinal (GI) tract has not been fully elucidated. AIM: The aim of this
      study was to determine the presence and distribution of EBV in formalin-fixed
      paraffin-embedded tissue samples obtained from 18 Malaysian patients diagnosed
      with NHL of the lower GI tract. METHODS: The GI tract lymphoma tissue samples
      analyzed for the presence of EBV were divided into the following groups: NHL of
      the small intestine (seven cases); NHL of the ileocecum (ten cases); and NHL of
      the rectum (one case). The presence of EBV-encoded RNA (EBER) in all of the above
      tissue samples was tested for using conventional in situ hybridization
      technology. RESULTS: Two of 18 cases (11.1%) of NHL of the lower GI tract
      demonstrated positive signals for EBV/EBER. In the first positive case, EBV/EBER
      signals were located in lymphoma cells in the serosa layer of the small
      intestine. In the second EBV/EBER-positive case, EBV/EBER signals were detected
      in diffuse B-cell lymphoma of the ileocecum. CONCLUSION: These findings
      demonstrate a rare association between EBV and lower GI tract lymphomas in this
      group of Malaysian patients.

PMID- 16884330
TI  - Methamphetamine modulates gene expression patterns in monocyte derived mature
      dendritic cells: implications for HIV-1 pathogenesis.
AB  - BACKGROUND: The US is currently experiencing a grave epidemic of methamphetamine
      use as a recreational drug, and the risk for HIV-1 infection attributable to
      methamphetamine use continues to increase. Recent studies show a high prevalence
      of HIV infection among methamphetamine users. Dendritic cells (DCs) are potent
      antigen presenting cells that are the initial line of defense against HIV-1
      infection. In addition, DCs also serve as reservoirs for HIV-1 and function at
      the interface between the adaptive and the innate immune systems, which recognize
      and internalize pathogens and subsequently activate T cells. Exposure to
      methamphetamine results in modulation of immune functional parameters that are
      necessary for host defense. Chronic methamphetamine use can cause psychiatric co
      morbidity, neurological complications, and can alter normal biological processes
      and immune functions. Limited information is available on the mechanisms by which
      methamphetamine may influence immune function. This study explores the effect of
      methamphetamine on a specific array of genes that may modulate immune function.
      We hypothesize that methamphetamine treatment results in the immunomodulation of
      DC functions, leading to dysregulation of the immune system of the infected host.
      This suggests that methamphetamine has a role as a cofactor in the pathogenesis
      of HIV-1. METHODS: We used the high-throughput technology of gene microarray
      analysis to understand the molecular mechanisms underlying the genomic changes
      that alter normal biological processes when DCs are treated with methamphetamine.
      Additionally, we validated the results obtained from microarray experiments using
      a combination of quantitative real-time PCR and Western blot analysis. RESULTS:
      These data are the first evidence that methamphetamine modulates DC expression of
      several genes. Methamphetamine treatment alters categories of genes that are
      associated with chemokine regulation, cytokinesis, signal transduction
      mechanisms, apoptosis, and cell cycle regulation. This report focuses on a
      selected group of genes that are significantly modulated by methamphetamine
      treatment and that have been associated with HIV-1 pathogenesis.
      DISCUSSION/CONCLUSION: The purpose of this study was to identify genes that are
      unique and/or specific to the complex immunomodulatory mechanisms that are
      altered as a result of methamphetamine abuse in HIV-1-infected patients. These
      studies will help to identify the molecular mechanisms that underlie
      methamphetamine toxicity, and several functionally important classes of genes
      have emerged as targets in methamphetamine-mediated immunopathogenesis of HIV-1.
      Identification of novel DC-specific and methamphetamine-responsive genes that
      modulate several biological, molecular, and signal transduction functions may
      serve as methamphetamine- and/or HIV-1-specific drug targets.

PMID- 16884337
TI  - AIDS control in India: A perspective from the traditional medicine sector.

PMID- 16884338
TI  - Can herbal medicine assist against avian flu? Learning from the experience of
      using supplementary treatment with Chinese medicine on SARS or SARS-like
      infectious disease in 2003.

PMID- 16884331
TI  - Intrinsic disorder is a common feature of hub proteins from four eukaryotic
      interactomes.
AB  - Recent proteome-wide screening approaches have provided a wealth of information
      about interacting proteins in various organisms. To test for a potential
      association between protein connectivity and the amount of predicted structural
      disorder, the disorder propensities of proteins with various numbers of
      interacting partners from four eukaryotic organisms (Caenorhabditis elegans,
      Saccharomyces cerevisiae, Drosophila melanogaster, and Homo sapiens) were
      investigated. The results of PONDR VL-XT disorder analysis show that for all four
      studied organisms, hub proteins, defined here as those that interact with > or =
      10 partners, are significantly more disordered than end proteins, defined here as
      those that interact with just one partner. The proportion of predicted disordered
      residues, the average disorder score, and the number of predicted disordered
      regions of various lengths were higher overall in hubs than in ends. A binary
      classification of hubs and ends into ordered and disordered subclasses using the
      consensus prediction method showed a significant enrichment of wholly disordered
      proteins and a significant depletion of wholly ordered proteins in hubs relative
      to ends in worm, fly, and human. The functional annotation of yeast hubs and ends
      using GO categories and the correlation of these annotations with disorder
      predictions demonstrate that proteins with regulation, transcription, and
      development annotations are enriched in disorder, whereas proteins with catalytic
      activity, transport, and membrane localization annotations are depleted in
      disorder. The results of this study demonstrate that intrinsic structural
      disorder is a distinctive and common characteristic of eukaryotic hub proteins,
      and that disorder may serve as a determinant of protein interactivity.

PMID- 16884339
TI  - Effects of Huangqi Guizhi Wuwu Tang on diabetic peripheral neuropathy.

PMID- 16884340
TI  - More reasons to respect other medical paradigms.

PMID- 16884342
TI  - Where does hypnotherapy stand in the management of irritable bowel syndrome? A
      systematic review.
AB  - BACKGROUND: Irritable bowel syndrome (IBS) is a gastrointestinal disorder
      characterized by chronic abdominal pain and altered bowel habits in the absence
      of any organic cause. Despite its prevalence, there remains a significant lack of
      efficient medical treatment for IBS to date. However, according to some previous
      research studies, hypnosis has been shown to be effective in the treatment of
      IBS. AIM: To determine the definite efficacy of hypnosis in the treatment of
      irritable bowel syndrome. METHODS: A systematic review of the literature on
      hypnosis in the treatment of IBS from 1970 to 2005 was performed using MEDLINE.
      Full studies published in English were identified and selected for inclusion. We
      excluded case studies and those studies in which IBS symptoms were not in the
      list of outcome measures. All studies were reviewed on the basis of the Rome
      Working Team recommendations for design of IBS trials. RESULTS: From a total of
      22 studies, seven were excluded. The results of the reviewed studies showed
      improved status of all major symptoms of IBS, extracolonic symptoms, quality of
      life, anxiety, and depression. Furthermore these improvements lasted 2-5 years.
      CONCLUSIONS: Although there are some methodologic inadequacies, all studies show
      that hypnotherapy is highly effective for patients with refractory IBS, but
      definite efficacy of hypnosis in the treatment of IBS remains unclear due to lack
      of controlled trials supporting this finding.

PMID- 16884341
TI  - Impact of a massage therapy clinical trial on immune status in young Dominican
      children infected with HIV-1.
AB  - PURPOSE: The effectiveness of massage therapy on immune parameters was evaluated
      in young Dominican HIV+ children without current access to antiretroviral
      therapies. METHODS: Eligible children, who were followed at the Robert Reid
      Cabral Hospital (San Domingo, Dominican Republic), were randomized to receive
      either massage treatment or a control/friendly visit twice weekly for 12 weeks.
      Blood was drawn at baseline and following the 3-month intervention for
      determinations of CD4, CD8, and CD56 cell counts and percentage, along with
      activation markers (CD25 and CD69). RESULTS: Despite similar immune parameters at
      baseline in the two groups, significantly more of the control group exhibited a
      decline in CD4 cell count (>30%, p = 0.03), postintervention. The decrease was
      particularly evident in older (5-8 years) children in the control arm, who
      demonstrated a significant reduction in both CD4 and CD8 cell counts compared to
      massage-treated older children who remained stable or showed immune improvement.
      Additionally, a significant increase in CD4+CD25+ cells was observed over the 12
      week trial in the massage-treated older children (p = 0.04) but not in the
      control group. In younger massage-treated children, (2-4 years old), a
      significant increase in natural killer cells was shown. CONCLUSION: Together
      these findings support the role for massage therapy in immune preservation in
      HIV+ children.

PMID- 16884343
TI  - Reporting traditional Chinese medicine morbidity--A University of Technology,
      Sydney, project with an emphasis on developing standards for testing and
      reporting data.
AB  - OBJECTIVES: Morbidity in Traditional Chinese Medicine (TCM) research is an
      emerging field. Few studies have been published, and there is a lack of
      international standards for data collection and reporting. Based on the
      experience of developing a computerized system for patient data collection at the
      University of Technology, Sydney, (UTS) Acupuncture Clinic (Sydney, Australia),
      and reporting results from that database, a start can be made toward developing
      guidelines for reporting similar results from TCM clinical audits. METHODS: This
      study reports on data relating to 5735 patients who had undergone 29,697
      treatments. Patient information is collected by a computerized database recording
      International Classification of Primary Care (ICPC) reason for encounter (RFE)
      and symptom for encounter (SFE) data and TCM tongue, pulse, diagnostic, and
      treatment data. Data coding is automated, and systems for reliability testing and
      error reporting were developed. RESULTS: UTS data has a 2.7% error rate and is
      within international standards of 5% error. Sixty-one-point three percent (61.3%)
      of patients were female and of these, 59.45 were 25-44 years of age.
      Musculoskeletal disorders are the most common presentation (41.4%) of all RFE,
      followed by general disorders (13.1%) and digestive disorders (8.1%).
      CONCLUSIONS: International standards must be set for TCM morbidity data
      collection methods and reporting. It is hoped that the methods described and
      reported in this paper are an initial step in the setting of such standards and
      that they will be adopted by other researchers. In particular, methods for
      testing and reporting data reliability must be adopted if TCM morbidity studies
      are to maintain any credibility.

PMID- 16884344
TI  - Effect of aromatherapy on symptoms of dysmenorrhea in college students: A
      randomized placebo-controlled clinical trial.
AB  - OBJECTIVE: The purpose of this study was to explore the effect of aromatherapy on
      menstrual cramps and symptoms of dysmenorrhea. DESIGN: The study was a randomized
      placebo-controlled trial. SUBJECTS: The subjects were 67 female college students
      who rated their menstrual cramps to be greater than 6 on a 10-point visual
      analogue scale, who had no systemic or reproductive diseases, and who did not use
      contraceptive drugs. INTERVENTION: Subjects were randomized into three groups:
      (1) an experimental group (n = 25) who received aromatherapy, (2) a placebo group
      (n = 20), and (3) a control group (n = 22). Aromatherapy was applied topically to
      the experimental group in the form of an abdominal massage using two drops of
      lavender (Lavandula officinalis), one drop of clary sage (Salvia sclarea), and
      one drop of rose (Rosa centifolia) in 5 cc of almond oil. The placebo group
      received the same treatment but with almond oil only, and the control group
      received no treatment. OUTCOME MEASURES: The menstrual cramps levels was assessed
      using a visual analogue scale and severity of dysmenorrhea was measured with a
      verbal multidimensional scoring system. RESULTS: The menstrual cramps were
      significantly lowered in the aromatherapy group than in the other two groups at
      both post-test time points (first and second day of menstruation after
      treatment). From the multiple regression aromatherapy was found to be associated
      with the changes in menstrual cramp levels (first day: Beta = -2.48, 95% CI: 
      3.68 to -1.29, p < 0.001; second day: Beta = -1.97, 95% CI: -3.66 to -0.29, p =
      0.02 and the severity of dysmenorrhea (first day: Beta = 0.31, 95% CI: 0.05 to
      0.57, p = 0.02; second day: Beta = 0.33, 95% CI: 0.10 to 0.56, p = 0.006) than
      that found in the other two groups. CONCLUSIONS: These findings suggest that
      aromatherapy using topically applied lavender, clary sage, and rose is effective
      in decreasing the severity of menstrual cramps. Aromatherapy can be offered as
      part of the nursing care to women experiencing menstrual cramps or dysmenorrhea.

PMID- 16884345
TI  - Pharmacokinetic profile of the isoflavone puerarin after acute and repeated
      administration of a novel kudzu extract to human volunteers.
AB  - OBJECTIVES: This study was undertaken to assess the pharmacokinetic profile of
      puerarin, the major isoflavone found in a kudzu (Pueraria lobata) extract after
      acute and repeated administration. METHODS: Participants were given either single
      or repeated doses of kudzu extract, and blood samples were collected for either 8
      or 72 hours for subsequent pharmacokinetic analyses of puerarin. RESULTS: Using
      WinNonlin pharmacokinetic data analysis software, puerarin was found to be
      rapidly absorbed via the oral route, reach peak levels at 2 hours, and have a
      half-life of approximately 4.3 hours. The elimination half-life was not
      significantly altered after repeated administration. CONCLUSIONS: A formulation
      of kudzu extract delivers a large amount of the principal isoflavone in a rapid
      manner. The elimination rate constants and the mono-exponential decline in blood
      levels suggest that a one compartment model adequately explains how puerarin is
      handled by the body. Three times a day dosing is recommended as accumulation will
      not occur, and plasma levels remain at levels that are biologically active, even
      8 hours after the last steady-state dose.

PMID- 16884346
TI  - Demographic characteristics and perceived health status of users of folk
      therapies in Taiwan.
AB  - OBJECTIVES: This study examined the prevalence of folk therapy use among
      Taiwanese adults and factors associated with such use. SUBJECTS AND METHODS: The
      data used in this study were from the 2001 National Health Interview Survey in
      Taiwan, which utilized a multistaged stratified systematic sampling scheme.
      Included in the current analysis were 11,290 individuals from 20 to 65 years.
      RESULTS: Only 1.3% of those surveyed were classified as users of folk therapy.
      Users of folk therapies were older (p = 0.002), had higher annual incomes (p <
      0.001), and experienced more health problems (p = 0.006) than nonusers. The two
      groups were comparable in the areas of marital status, employment status, gender,
      and educational level. Users had lower scores in the physical functioning (p <
      0.001), role physical (p = 0.041), general health perception (p = 0.002), and
      bodily pain (p < 0.001) domains of the Medical Outcome Studies 36-Item Short-Form
      Health Survey. The two groups were not significantly different regarding the
      utilization and satisfaction with conventional medical resources and the domain
      scores of the brief version of the World Health Organization Quality of Life
      (QOL) questionnaire. CONCLUSIONS: Less than 2% of adult Taiwanese population
      reported relying primarily on folk therapies for their common physical
      discomfort. Users of folk therapies are older, have higher incomes, and have more
      health problems and poorer health-related QOL, but they neither make more
      frequent use of conventional medical services nor are they dissatisfied with the
      available services.

PMID- 16884347
TI  - Use of herbal/natural supplements according to racial/ethnic group.
AB  - OBJECTIVES: The aim of this paper was to determine similarities and differences
      in the use of herbal/natural supplements among various racial/ethnic groups.
      DESIGN: A random-digit dial (RDD) telephone survey of medication use during the
      week before the interview was used. SETTINGS/LOCATION: Households in the 48
      contiguous United States comprised our study. SUBJECTS: One (1) subject was
      selected by a random procedure from each contacted household, including
      interviews conducted from 1998 through September 2004. There were 13,436 subjects
      at least 18 years of age, including 10,372 non-Hispanic whites, 1174 African
      Americans, 1109 Hispanics, 335 Asian/Pacific Islanders, and 446 others. OUTCOME
      MEASURES: Use of any herbal/natural product during the prior week served as
      outcome measures. Prevalence of use was weighted according to household size; for
      comparisons among the three largest groups, estimates were also adjusted for age,
      gender, and education. RESULTS: The overall prevalence was lowest in African
      Americans (9.5%; 95% confidence interval [CI], 7.8%-11%), intermediate in
      Hispanics (12%; 10%-14%), and highest in non-Hispanic whites (19%; 18%-20%). Use
      was higher among women and generally higher for subjects 45-64 years of age,
      regardless of race/ethnicity; use increased with increasing years of education.
      The most commonly taken individual herbal/natural substances were similar among
      the groups. Hispanics used the largest number of products. Distribution of
      product type differed somewhat, with Hispanics taking more monopreparations and
      herbal mixtures than the other groups, and herbal mixture use particularly
      uncommon among African Americans. Use between 1998 and 2004 increased slightly
      for non-Hispanic whites, increased then declined for African Americans, and did
      not change for Hispanics. CONCLUSIONS: Based on nationally representative U.S.
      data, these results provide a comparative picture of contemporary use of
      herbal/natural supplements in the largest racial/ethnic groups in the United
      States. The prevalence of use was lowest among African Americans, with a possible
      decline in recent years, whereas Hispanics take the greatest number of products.

PMID- 16884348
TI  - HIV/AIDS: Traditional systems of health care in the management of a global
      epidemic.
AB  - Cultural preference and the high cost and unavailability of anti-HIV drugs for
      people living with HIV/AIDS in the developing world leads many to turn to
      traditional (indigenous) medicine to manage HIV-related illness. Traditional
      health practitioners can play an important role in delivering an AIDS prevention
      message and some may be able to offer treatment for opportunistic infections. In
      industrialized countries, approximately half or more of those with AIDS use
      complementary medicines in conjunction with their antiretroviral therapy. A
      growing body of research highlights the immunomodulatory and antiviral potential
      of plant-based medicines. There are also concerns about unsafe practices and a
      growth in claims of traditional cures for AIDS. Partnerships between the modern
      and traditional/complementary health sectors in research, policy, and practice
      are essential in building comprehensive HIV/AIDS control strategies.

PMID- 16884349
TI  - Biomedical orthodoxy and complementary and alternative medicine: Ethical
      challenges of integrating medical cultures.
AB  - This paper examines biomedicine's contemporary overture to complementary and
      alternative medicine (CAM) in the move toward an integrated medical system. The
      paper argues that a major challenge of our increasingly integrating medical
      culture is raising commensurate personnel to grapple with the changing ethical
      landscape, especially with regard to understanding the methodologies and
      philosophies of CAM's therapeutic paradigms. Such personnel is required to tackle
      realistically the critical ethical challenge of our amalgamating medical system,
      namely an acceptable framework for evaluating the efficacy of CAM's plural
      therapeutic paradigms.

PMID- 16884356
TI  - Gynecological cancers in developing countries: the challenge of chemotherapy in
      low-resources setting.
AB  - The epidemiologic pattern of cancers in developing countries differs in many
      aspects from that of industrialized nations. Cancer natural history,
      microbiologic environment, patient's immune system, and drug availability may
      differ as well. Four of five new cases of cervical cancer and most of cervical
      cancer deaths occur in developing countries. Where chemoradiation and supportive
      care facilities are unavailable, it would be logical to consider an inexpensive
      effective drug. In locally advanced cases, neoadjuvant chemotherapy followed by
      surgery should be considered the treatment of choice. For ovarian cancer, it may
      be reasonable to maintain a secure supply of platinum and/or taxanes. For
      endometrial cancer, platinum compounds are proved active chemotherapic single
      agents. Oral medroxyprogesterone acetate (MPA) may represent a good chance for
      treating an advanced or recurrent disease. For vulvar/vaginal cancer, the role of
      chemotherapy alone is currently considered limited, and it is mostly used as
      palliative treatment in advanced or recurrent cases. Whenever possible, standard
      western chemotherapic regimens should be applied in developing countries as well.
      When standard therapies are unavailable, drugs of choice should be easily
      accessible, inexpensive, and effective. The most commonly used drugs are
      cisplatin, cyclophosphamide, and MPA.

PMID- 16884357
TI  - Who should be vaccinated against human papillomavirus?

PMID- 16884355
TI  - Tankyrase recruitment to the lateral membrane in polarized epithelial cells:
      regulation by cell-cell contact and protein poly(ADP-ribosyl)ation.
AB  - PARsylation [poly(ADP-ribosyl)ation] of proteins is implicated in the regulation
      of diverse physiological processes. Tankyrase is a molecular scaffold with this
      catalytic activity and has been proposed as a regulator of vesicular trafficking
      on the basis, in part, of its Golgi localization in non-polarized cells. Little
      is known about tankyrase localization in polarized epithelial cells. Using MDCK
      (Madin-Darby canine kidney) cells as a model, we found that E-cadherin-mediated
      intercellular adhesion recruits tankyrase from the cytoplasm to the lateral
      membrane (including the tight junction), where it stably associates with
      detergent-insoluble structures. This recruitment is mostly completed within 8 h
      of calcium-induced formation of cell-cell contact. Conversely, when intercellular
      adhesion is disrupted by calcium deprivation, tankyrase returns from the lateral
      membrane to the cytoplasm and becomes more soluble in detergents. The PARsylating
      activity of tankyrase promotes its dissociation from the lateral membrane as well
      as its ubiquitination and proteasome-mediated degradation, resulting in an
      apparent protein half-life of approximately 2 h. Inhibition of tankyrase
      autoPARsylation using H2O2-induced NAD+ depletion or PJ34 [N-(6-oxo-5,6
      dihydrophenanthridin-2-yl)-N,N-dimethylacetamide hydrochloride] treatment results
      in tankyrase stabilization and accumulation at the lateral membrane. By contrast,
      stabilization through proteasome inhibition results in tankyrase accumulation in
      the cytoplasm. These data suggest that cell-cell contact promotes tankyrase
      association with the lateral membrane, whereas PARsylating activity promotes
      translocation to the cytosol, which is followed by ubiquitination and proteasome
      mediated degradation. Since the lateral membrane is a sorting station that
      ensures domain-specific delivery of basolateral membrane proteins, the regulated
      tankyrase recruitment to this site is consistent with a role in polarized protein
      targeting in epithelial cells.

PMID- 16884359
TI  - Gynecological tumors revealing hereditary nonpolyposis colorectal cancer:
      analysis of a large Lebanese pedigree.
AB  - The objective of this study was to evaluate the aggregation of colorectal cancer
      (CRC) and hereditary nonpolyposis colorectal cancer (HNPCC)-related extracolonic
      cancers in an extended Lebanese family with HNPCC. This was a pedigree analysis
      and a prospective follow-up over an 8-year period. The causative germ line
      mutation was detected using denaturing high-performance liquid chromatography,
      polymerase chain reaction (PCR) of short fluorescent fragments, and direct DNA
      sequencing of purified PCR products. The penetrance of CRC is high and accounts
      for approximately two thirds of risk carriers with an early age of onset (21
      years). The extracolonic cancer spectrum includes ovary, endometrium, small
      bowel, skin, and brain, with an age of onset as early as 30 years. The causative
      mismatch repair gene mutation is an MSH2 point mutation involving the splice
      donor site of intron 3 (G-->A). Scrutinized in genomic DNA from 35 consented
      members, it was found in 18 of them and cosegregates with the cancer phenotype in
      the family. Early-onset ovarian and endometrial carcinomas may reveal HNPCC
      families in the Middle Eastern region, with MSH2 germ line mutation. We propose a
      biannual screening program, starting around the age of 20-25 years, pending
      additional data on this topic.

PMID- 16884358
TI  - Immunobiology of gestational trophoblastic diseases.
AB  - Gestational trophoblastic diseases (GTDs) comprise a group of interrelated
      diseases characterized by development after gestation, widespread metastases, and
      high curability with chemotherapy. The good prognosis of GTDs is considered
      partly a result of the host immune response to paternal antigens expressed on
      trophoblastic cells. In this study, we review current understanding of the
      immunobiology of GTDs. First of all, we describe the microenvironment between
      trophoblastic cells and subpopulation of immune cells. Second, immunogenetics,
      immune microenvironment around abnormal trophoblast, and mechanism of GTDs
      escaping from maternal immune system surveillance were also discussed. Third, we
      propose the possible immunotherapy for persistent GTDs, particularly the vaccine
      designed on human chorionic gonadotrophin, which is generally accepted as a tumor
      marker for GTDs diagnosis. Due to the low incidence of GTDs and high response to
      chemotherapy, there have been few literatures about immunobiologic
      characteristics of GTDs compared with the other gynecologic malignancies, such as
      ovarian cancer, but the immunologic behavior of GTDs should be explored for
      further understanding of the etiology of these diseases and to help designing
      immunotherapeutic strategies for persistent GTDs.

PMID- 16884360
TI  - Interferon-gamma in combination with carboplatin and paclitaxel as a safe and
      effective first-line treatment option for advanced ovarian cancer: results of a
      phase I/II study.
AB  - We have previously shown that interferon-gamma 1b (IFN-gamma) in combination with
      cyclophosphamide and cisplatin significantly prolongs progression-free survival
      in ovarian cancer. In this phase I/II study, we examined if administration of IFN
      gamma is also safe in combination with the current standard treatment, paclitaxel
      and carboplatin. Thirty-four patients with newly diagnosed advanced epithelial
      ovarian cancer, FIGO stage III/IV, were treated for six to nine cycles with
      paclitaxel (175 mg/m(2)) and carboplatin (area under the curve [AUC] 5) every 3
      weeks. IFN-gamma was administered in an escalating dose from 6 days/cycle with
      0.025 mg sc up to 9 days/cycle with 0.1 mg sc. As expected, administration of IFN
      gamma was associated with flu-like symptoms. Grade 3/4 neutropenia was observed
      in 74% (25 out of 34) of patients. Other side effects, in particular peripheral
      neuropathies, were within the previously observed ranges for the paclitaxel plus
      carboplatin combination. Overall response rate (complete or partial response) in
      patients who received either six or nine doses (0.1 mg) of IFN-gamma/cycle (n =
      28) was 71%. IFN-gamma is safe in combination with carboplatin and paclitaxel for
      first-line treatment of patients with advanced ovarian cancer. This combination
      should be further evaluated as an immunotherapeutic treatment option for ovarian
      cancer.

PMID- 16884361
TI  - High expression of insulin-like growth factor binding protein-2 messenger RNA in
      epithelial ovarian cancers produces elevated preoperative serum levels.
AB  - The molecular etiology of epithelial ovarian cancer remains unclear. Using
      microarray expression analysis, we recently reported that expression of the
      insulin-like growth factor binding protein-2 (IGFBP-2) gene is elevated in
      advanced epithelial ovarian cancers. The aim of this study was to further
      delineate the role of IGFBP-2 in the pathoetiology of epithelial ovarian cancer
      and determine if elevated ovarian cancer IGFBP-2 gene expression is reflected in
      serum. Relative IGFBP-2 expression was measured using quantitative real-time
      polymerase chain reaction in 113 epithelial ovarian cancers and 6 normal ovarian
      surface epithelial samples. Preoperative serum IGFBP-2 levels were measured by
      radioimmunoassay in 84 women (42 ovarian cancers, 26 benign gynecological
      conditions, and 10 healthy female controls). Ovarian cancers demonstrated 38-fold
      higher mean IGFBP-2 expression than normal ovarian epithelium (P < 0.01). Serum
      IGFBP-2 levels were elevated in women with early- and advanced-stage ovarian
      cancer compared to controls and patients with benign gynecological conditions (P
      = 0.05 and P < 0.01, respectively). Epithelial ovarian cancers express high
      levels of IGFBP-2 relative to normal ovarian epithelium, and this is associated
      with elevated serum IGFBP-2 levels compared to both normal controls and patients
      with benign gynecological disease. Our findings provide further support that the
      insulin-like growth factor pathway plays a significant role in epithelial ovarian
      cancer pathogenesis. Further, IGFBP-2 may represent an additional serum biomarker
      with utility in detection and monitoring of epithelial ovarian cancer.

PMID- 16884362
TI  - Human ovarian cancer ascites fluid contains a mixture of incompletely degraded
      soluble products of fibrin that collectively possess an antiangiogenic property.
AB  - Ovarian cancer ascites fluid (OCAF) displayed an antiangiogenic property in a
      chick chorioallantoic membrane (CAM) assay. This property was attributed in part
      to angiostatin although angiostatin-free OCAF retained a net antiangiogenic
      property. Recently, immunopurified fibrin(ogen) degradation products (FDPs) from
      malignant effusions of VX2 tumor-burdened rabbits exhibited antiangiogenic
      activity on the CAM. We questioned whether the FDPs of OCAF were also
      antiangiogenic. FDPs were immunopurified from individual OCAF samples,
      characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis
      /western blots, enzyme-linked immunosorbent assays, and CAM assays. FDPs of OCAFs
      consisted of soluble high molecular weight (MW) fragments (>200 kd; approximately
      40% of total FDPs), D-dimer (approximately 180 kd; approximately 37%), fragment D
      (approximately 90 kd; approximately 15%), and fragment E (approximately 50 kd;
      approximately 8%); intact fibrinogen was absent. When applied to CAM surfaces
      (0.5-1.6 mg/10 mL), purified FDPs significantly reduced the area of chorionic
      capillaries from 90% (in controls) to 47% over a 48-h period; from CAM sections,
      capillary density was reduced from 60% (controls) to 26%. FDPs prepared from
      fibrinogen displayed a similar antiangiogenic effect. Further digestion of OCAF
      FDPs by human plasmin caused degradation of high MW fragments, releasing
      additional D-dimer, fragment D, and fragment E. Of the fibrinogen-related
      components, OCAF contained only soluble FDPs (including incompletely digested
      fibrin fragments). Collectively, these FDPs contributed to the net antiangiogenic
      property of ascites fluid.

PMID- 16884363
TI  - Activation of mammalian target of rapamycin in postmenopausal ovarian
      endometriosis.
AB  - The purpose of this study was to determine whether Akt and mammalian target of
      rapamycin (mTOR), downstream targets of phosphatidylinositol 3-kinase, are
      activated in endometriosis and ovarian cancer specimens. We measured total and
      phosphorylated levels of Akt and mTOR from 17 frozen ovarian cancers and 15
      benign endometriosis specimens (nine from premenopausal women and six from
      postmenopausal women) by quantitation of signals from western blots using
      antibodies against these proteins. Elevated phospho-Akt was detected in ovarian
      cancer versus endometriosis specimens from premenopausal women and endometriosis
      specimens from postmenopausal women (2.3 +/- 0.45 versus 0.10 +/- 0.06 and 0.17
      +/- 0.11; P < 0.05) when the western blot signal of activated kinase was
      normalized to total kinase levels. Elevated phospho-mTOR was detected in ovarian
      cancer and postmenopausal endometriosis versus premenopausal endometriosis (0.52
      +/- 0.19 and 0.46 +/- 0.29 versus 0.13 +/- 0.08; P < 0.05). Expression of total
      kinases (normalized to beta-actin) was higher in carcinoma versus endometriosis
      specimens. Elevation of the active mTOR was specifically detected in
      postmenopausal endometriosis.

PMID- 16884364
TI  - Arsenic trioxide exposure to ovarian carcinoma cells leads to decreased level of
      topoisomerase II and cytotoxicity.
AB  - The objective of this study was to investigate the effect of arsenic trioxide
      (As(2)O(3)) on topoisomerase II levels using western blotting method on MDAH 2774
      ovarian carcinoma cell culture. Experimental designs were established to
      determine the cytotoxic effects of As(2)O(3) on MDAH 2774 cells and the IC50
      (fatal dose for the 50% of cells) value. Cytotoxicity experiments were carried
      out using various concentrations of As(2)O(3). The 2,3-bis[2-methyloxy-4-nitro-5
      sulfophenyl]-2H-tetrazolium-5-carboxanilide (XTT) and trypan blue dye-exclusion
      tests were used to evaluate cytotoxicity. Topoisomerase II expressions were
      investigated using western blotting method with various concentrations of
      As(2)O(3). Densitometric analysis of topoisomerase 2 bands was carried out using
      Quantity One 1-D analysis software (Bio-Rad USA, Life Science Research, Hercules,
      CA). IC50 value of As(2)O(3) was found to be 5 x 10(-6) M for MDAH 2774 cells.
      When the bands were evaluated, it was observed that there was a decrease in
      topoisomerase II levels in MDAH 2774 cells with increasing concentrations of
      As(2)O(3). It was also observed by the densitometric analysis that topoisomerase
      II expression ratios of MDAH 2774 cells were decreased by approximately 50% at
      this concentration. Topoisomerase II levels were significantly decreased with the
      increasing concentrations of As(2)O(3). Inhibition of topoisomerase II enzyme was
      one of the antiproliferative influence mechanisms of As(2)O(3).

PMID- 16884365
TI  - Combretastatin A-1 phosphate potentiates the antitumor activity of carboplatin
      and paclitaxel in a severe combined immunodeficiency disease (SCID) mouse model
      of human ovarian carcinoma.
AB  - In search for new therapeutic modalities to target epithelial ovarian carcinomas,
      we investigated the effect of the antiangiogenic drug combretastatin A-1
      phosphate (CA1P) as a single treatment or in combination with established
      therapy, ie, carboplatin and paclitaxel. Five different human epithelial ovarian
      carcinoma cell lines were inoculated subcutaneously into FOX CHASE CB-77 severe
      combined immunodeficiency disease (SCID) mice. When tumors reached a volume of
      approximately 100 mm(3), the treatment was initiated. All drugs were given
      intraperitoneally at weekly doses. CA1P was more effective as an antitumor agent
      than combretastatin A-4 phosphate as a single-drug treatment or in combination
      with carboplatin and paclitaxel. CA1P had a strong tumor outgrowth inhibiting
      effect on four out of five tumors included in this study. Comparing animals
      receiving CA1P with animals receiving a combination of carboplatin and
      paclitaxel, CA1P was more effective on two out of three tested tumors, whereas
      carboplatin and paclitaxel were more effective on one out of three of the tumors.
      We show that treatment of human ovarian carcinomas with CA1P in the SCID mouse
      model results in a strong antitumor effect both as a single-drug treatment and as
      an enhancement of the therapeutic effect in a combination treatment protocol with
      carboplatin and paclitaxel.

PMID- 16884366
TI  - Women in a region with high incidence of cervical cancer warrant immediate
      colposcopy for low-grade squamous intraepithelial lesion on cervical cytology.
AB  - The objective of this study was to determine the prevalence of high-grade
      histologic diagnoses in women who had low-grade squamous intraepithelial lesion
      (LSIL) on Pap smear in an area with high incidence of cervical cancer. We
      conducted a retrospective study of 220 women with LSIL cytology undergoing
      colposcopic examination in Chiang Mai University Hospital between January 1999
      and July 2004. The histologic diagnoses, obtained from colposcopically directed
      biopsy or electrical loop excision after initial colposcopy, showed that 80
      (36.4%) women had histologically confirmed high-grade lesions and 11 (5%) women
      had microinvasive (9) and frankly invasive (2) carcinomas. Overall, 41.5% of
      women with LSIL on Pap smear had significant underlying lesions, requiring
      appropriate treatment. In conclusion, in the region with high incidence of
      cervical cancer, women with LSIL cytology are at increased risk of having
      underlying high-grade lesions and invasive cancer. Immediate referral for
      colposcopy is warranted.

PMID- 16884367
TI  - What is the difference between squamous cell carcinoma and adenocarcinoma of the
      cervix? A matched case-control study.
AB  - The objective of this study was to investigate the efficacy of treatment
      strategies in patients with adenocarcinoma (AC) of the cervix and compare it with
      those with squamous cell carcinoma (SCC) of the cervix. Women with FIGO (1994)
      stage IB1 AC, especially pathologic tumor size of 2-4 cm, treated with class III
      hysterectomy, were compared with those with SCC treated with comparable strategy
      in a case-controlled study. Eighty patients (20 cases, 60 controls) were
      analyzed. Lymphvascular space invasion (P = 0.01) and lymph node metastasis (P =
      0.07) were more frequent in patients with SCC than in those with AC. However,
      there was no significant difference in depth of stromal invasion (P = 0.51) and
      invasion of the parametrium (P = 0.44) between two groups. And there was also no
      statistically significant difference in disease-free survival (P = 0.86) and
      overall survival (P = 0.89) between two groups. Primary radical surgery followed
      by adjuvant therapy, same as for SCC, would be acceptable for AC with pathologic
      tumor size of 2-4 cm. Although it was difficult to determine whether AC recurred
      more systemically, more effective treatment strategies than those currently
      available for AC should be considered to reduce the systemic recurrence.

PMID- 16884369
TI  - A comparative study of two devices used for cervical cell sampling raises some
      doubts about liquid-based cytology.
AB  - The objective of this study was to compare the quality of smears obtained by a
      newly designed cervical cell sampler (the implement) to those obtained with the
      cervex brush, using liquid-based cytology (LBC). A prospective randomized
      controlled trial with the approval of the local ethics committees after informing
      the Medical Devices Agency in the UK was used in this study. The study was
      carried out in colposcopy clinics in two district general NHS Trust Hospitals in
      London. A total of 200 women were recruited (100 from each hospital). The women
      were randomized into two groups, each of them having two smears at the same time.
      One hundred (50%) of the women had their first smear with the new implement, and
      the other 100 (50%) had their first smear with the cervex brush. The main outcome
      of this study is good-quality smears, assessed by evidence of effective sampling
      of the transformation zone, including immature metaplastic cells and also
      endocervical cells. Eighty-five percent of the smears taken by the new implement
      showed good-quality smears compared to 91% of those taken by the cervex brush, a
      statistically marginally nonsignificant result, with P value = 0.052 (McNemar
      exact test). A larger number of good-quality smears, judged by evidence of
      sampling of transformation zone, were obtained with the cervex brush, though the
      difference was statistically marginally nonsignificant, using the British society
      for clinical cytology criteria. Surprisingly, despite the use of LBC, there was a
      higher rate of inadequate smears obtained with both the devices (8% with each)
      compared to our previous study using the conventional slide test (1.3% with the
      new implement and 1.8% with the Jordan's spatula).

PMID- 16884370
TI  - Urine cytology as a screening test for bladder infiltration in cervical cancer.
AB  - Ultrasound is currently used as a screening test for bladder infiltration in
      patients with advanced-stage cervical cancer at our institution. Cystoscopy is
      reserved for patients with abnormal bladder ultrasound findings. This study was
      undertaken to reevaluate this policy and to compare the results of different
      screening tests. The study was carried out in Pretoria academic complex. All
      newly diagnosed cervical carcinoma patients stage II and above were included in
      this study. The standard staging investigations were done on all patients. In
      addition, urine midstream and catheter specimens were sent for cytology.
      Cystoscopy and biopsy were performed on all patients. Two hundred twenty-eight
      patients were enrolled into this study. At cystoscopy, 47 patients had bladder
      mucosa suspicious of malignant infiltration, of which 17 had bladder mucosa
      infiltration diagnosed on histology. Urine catheter cytology has a sensitivity of
      94% and specificity of 82% for bladder mucosa infiltration. The predictive value
      of a positive test is 31% and for a negative test is 99%. Catheter urine cytology
      is a very useful screening test for bladder infiltration in patients with
      cervical cancer. Cystoscopy should be reserved for patients with abnormal urine
      cytology in resource-poor settings with a large burden of disease.

PMID- 16884368
TI  - Loop conization for the treatment of microinvasive carcinoma of the cervix.
AB  - The purpose of the study was to evaluate the specimen adequacy and diagnostic
      accuracy of loop conization in microinvasive carcinoma of the cervix. A
      retrospective study was conducted from 1997 to 2003 at the Colposcopic Clinic,
      Department of Gynecology and Obstetrics, Chang Gung Memorial Hospital, Taipei,
      Taiwan. Sixty-three consecutive patients with microinvasive carcinoma of the
      cervix receiving cold-knife conization (35 patients) or loop conization (28
      patients) were included in the study. All patients underwent definitive
      hysterectomy. We reviewed the conization specimen together with the
      hysterectomied uterus to compare the two conization techniques with respect to
      the histopathologic interpretation and diagnostic accuracy. The mean depth of
      cone specimens was significantly less in the loop conization compared with cold
      knife conization (1.65 versus 2.35 cm, P = 0.035). Regarding the application of
      conization, the loop conization was completed in a single slice in 27 patients
      (77.1%) and in multiple slices in 8 patients (22.9 %), in spite of encouragement
      to perform conization in a one-pass application when possible. However, the cold
      knife specimens were invariably a single cone-shaped piece. As reviewed by
      microscopic examination, the rate of tissue transection was significantly higher
      in the loop group than in the cold-knife group (14.3% versus 0%, P = 0.04).
      Because of tissue transection and disorientation, pathologic evaluation of
      stromal status was inadequate in 11.4% (4/35) of the loop cones as opposed to
      none of the 28 cold-knife cones. After assessing the hysterectomy specimens, the
      clinical diagnoses in the loop group were downgraded in three patients compared
      with only one in the cold-knife group. Data from this investigation suggest that
      cervical cold-knife conization is superior to loop conization as a method to
      assess microinvasive cervical cancer.

PMID- 16884371
TI  - Human papillomavirus genotypes associated with cervical neoplasia in India.
AB  - The aim of this study was to determine the prevalence of human papillomavirus
      (HPV) genotypes in tissue with cervical neoplasias in patients from south and
      east India. Cross-sectional cervical tissue was obtained from 100 patients from
      south India and 30 patients from east India who had a biopsy for clinically
      invasive cervical cancer or cervical intraepithelial neoplasia (CIN) in a
      tertiary care hospital in India. DNA amplification was done with biotinylated
      PGMY 09/11 primers, and the line blot assay was used to determine the HPV
      genotype. HPV DNA was detected in 95% of invasive cancers (113/119) and 91% of
      CINs (10/11). A single HPV type was found in 100 women (77%), and mixed
      infections were found in 23 women (18%). HPV 16 (60%) and HPV 18 (14%) were the
      most frequent types, but 16 other types (26, 31, 33, 35, 42, 45, 51, 52, 53, 56,
      58, 61, 62, 64, 81, and 82) were also identified. HPV 16 was present in 63% of
      patients from south India and in 50% of patients from east India, while HPV 18
      was present in 12% and 20%, respectively. There are several high-risk HPV types
      associated with cervical neoplasias of which types 16 and 18 are the most common.

PMID- 16884372
TI  - Candida and squamous (pre)neoplasia of immigrants and Dutch women as established
      in population-based cervical screening.
AB  - The objective of this study was to establish the relationship between Candida
      vaginalis and (pre)neoplasia and the prevalence of Candida and (pre)neoplasia
      related to age and ethnicity. Data were collected from 445,671 asymptomatic women
      invited for mass screening between 1995 and 2002 and coded according to the Dutch
      cervical smear coding system (KOPAC) with six grades for (pre)neoplastic changes.
      Prevalence and relative risks (RRs) were established for Candida and squamous
      abnormalities in Dutch women and four groups of immigrants. The prevalence of
      Candida is significantly higher in the cohort of 30-year-old women and lower in
      the cohorts of 45-, 50-, 55-, and 60-year-old women. The RR of having Candida was
      higher for Surinamese women (1.24; CI 1.08-1.42). Furthermore, the RR of having
      mild dysplasia was higher for Surinamese women (1.47; CI 1.14-1.89) and for women
      born in other countries than in The Netherlands, Turkey, and Morocco (1.36; CI
      1.13-1.62). No statistically significant relationship between (pre)neoplasia and
      Candida was observed. C. vaginalis is more frequent among Surinamese women.
      Presence of Candida is not associated with an increased risk for squamous
      abnormalities; therefore, women carrying Candida are not at an increased risk of
      developing cervical cancer.

PMID- 16884374
TI  - Risk factors for the progression or persistence of untreated mild dysplasia of
      the uterine cervix.
AB  - To identify the factors that may predict the progression or persistence of
      untreated mild dysplasia of the uterine cervix, we performed a retrospective
      review of 118 patients with histologically verified mild dysplasia who underwent
      colposcopic biopsies between January 1999 and December 2003. Regression to normal
      occurred in 70.3%, progression to moderate dysplasia or worse occurred in 11.0%,
      and persistence of mild dysplasia occurred in 18.7%. In regression/progression
      analysis, progression of untreated mild dysplasia was 34.5% (10/29) in patients
      with high viral loads (> or =100 relative light units/positive control [RLU/PC])
      and 4.5% (3/67) in those with low viral loads (1 to <100 RLU/PC) and negative
      human papillomavirus (HPV) tests (P < 0.001). Women with high viral loads had a
      13-fold greater chance of progression of untreated mild dysplasia than those with
      low viral loads and negative HPV tests (CI: 2.494-95.297; P = 0.0022). Those
      associated with both positive smear and positive HPV test (12/45 = 26.7%) were at
      a greater risk of progression of untreated mild dysplasia as compared with those
      with positive smear and negative HPV (0/17 = 0.0%) or those with negative smear
      and positive HPV test (1/18 = 5.6%). Those with high viral loads and both with
      positive smear and positive HPV test should be followed closely because of their
      increased risk of progression of untreated mild dysplasia.

PMID- 16884373
TI  - Detection of human papillomavirus in organs of upper genital tract in women with
      cervical cancer.
AB  - In this study, we evaluated the presence of human papillomavirus (HPV) DNA in
      organs of the female upper genital tract, using nine hysterectomy and salpingo
      oophorectomy specimens affected by HPV-positive invasive cervical carcinomas, to
      establish if cervical HPV infection can spread to upper tracts of the female
      genital system. HPV DNA was evaluated by polymerase chain reaction (PCR) in all
      cervical carcinomas as well as in all tracts of the genital system. Then, these
      data were compared with the results obtained from PCR study of five other
      hysterectomy and salpingo-oophorectomy specimens (control cases). The criteria
      used for selection of the control cases were informed consent of the patients for
      research at the time of surgery, absence of neoplasms, absence of any anatomic
      lesion caused by HPV in cervix, and external genitalia. All selected cases were
      squamous cervical carcinomas. PCR analysis revealed HPV DNA in all cases of
      cervical carcinoma. The HPV DNA was detected as weak positivity on PCR analysis
      in other organs of the genital system. However, the distribution of HPV DNA
      varied in the various cases and in the different tracts of the same hysterectomy
      and salpingo-oophorectomy specimen. We believe that the HPV DNA, detected as a
      weakly positive signal, in the upper genital tract of patients who have a
      cervical squamous carcinoma could be a reflection of a latent HPV infection, as
      well as a sign of the existence of micrometastases containing HPV DNA, which
      cannot be detected by conventional histologic techniques.

PMID- 16884375
TI  - A phase I study of concurrent cisplatin chemotherapy in patients with carcinoma
      of the cervix receiving pelvic radiotherapy.
AB  - The purpose of this study was to evaluate the maximum tolerated dose (MTD) of
      weekly cisplatin in a sample population of South African patients with cervical
      carcinoma, when given in combination with radical pelvic irradiation. Patients
      with cervical carcinoma stage IB2-IIIB (without hydronephrosis) received up to
      six cycles of cisplatin at weekly intervals. Groups consisting of three patients
      each were treated at each of the three predetermined dose levels of cisplatin
      (20, 25, and 30 mg/m(2)). Eighteen patients were treated and evaluated for
      toxicity. All the patients who received 20 mg/m(2) (n = 3) and 25 mg/m(2) (n = 3)
      cisplatin had no dose-limiting toxicity (DLT). Four of the 12 patients who were
      given cisplatin 30 mg/m(2) experienced DLT with rising serum creatinine and
      declining creatinine clearance. The minimum creatinine clearance was 22 mL/min.
      The highest serum creatinine was 174 mumol/L. This study showed that a weekly
      dose of 25 mg/m(2) of cisplatin was the MTD when used in combination with pelvic
      irradiation for this sample of patients. This dose is lower than the recommended
      dose of cisplatin 40 mg/m(2)/week. The patients in this study may have reduced
      tolerance to higher doses of cisplatin, when compared to patients from Western
      countries.

PMID- 16884376
TI  - Enhanced radiation-mediated cell killing of human cervical cancer cells by small
      interference RNA silencing of ataxia telangiectasia-mutated protein.
AB  - The ataxia telangiectasia-mutated (ATM) protein, which is mutated in the
      inherited disease ataxia telangiectasia (AT), is a key activator of cell cycle
      checkpoint, initiating cell response to DNA damage and ensuring genomic
      stability. AT cells exhibit defects in all cellular responses to ionizing
      radiation and radiomimetic chemicals. Inactivation of ATM may therefore make
      cells fail to execute many responses to DNA damage and improve the cells'
      sensitivity to radiation. Recent developments in the use of small interference
      RNA molecules (siRNAs) to inhibit specific protein expression have highlighted
      the potential use of siRNA as a therapeutic agent. In this study, we have
      designed and exogenously delivered plasmids encoding siRNAs targeting ATM to
      human cervical carcinoma SiHa cells and generated a stable cell line, SiHa(ATM).
      SiHa(ATM) cells displayed minimal levels of ATM protein and showed a marked
      increase in sensitivity to radiation. Together, these data provide strong
      evidence for the potential use of siRNA as a novel radiation/chemotherapy
      sensitizing agent.

PMID- 16884378
TI  - Reverse transcription-polymerase chain reaction and western blotting analysis for
      detection of p63 isoforms in uterine cervical cancers.
AB  - The aim of this study was to investigate the role of TAp63 and DeltaNp63 isoforms
      in uterine cervical cancers. The messenger RNA (mRNA) and protein expressions of
      TA and DeltaN forms as well as alpha, beta, and gamma isoforms of p63 were
      studied in seven SiHa, ME-180, SNU17, SNU902, SNU1160, SNU703, and SNU1299 human
      papillomavirus (HPV)-positive uterine cervical squamous cell carcinoma (SCC) cell
      lines, one HT3 HPV-negative SCC cell line, and one HeLa adenocarcinoma cell line
      using reverse transcription-polymerase chain reaction (RT-PCR) and western
      blotting. Fresh nonneoplastic and neoplastic tissues of uterine cervical and
      endometrial cancers were also studied. RT-PCR for TA and DeltaN form and three
      isoforms of p63 showed positive bands for both TA and DeltaN forms and for all
      three isoforms in cervical cancer cell lines but weak band for alpha isoform in
      HPV-negative HT3 SCC cell line and no band for beta isoform in HeLa
      adenocarcinoma cell line. RT-PCR for TA and DeltaN and three isoforms of p63 mRNA
      in tissue samples showed positive bands in almost all samples, except for gamma
      isoform, the expression was weak or absent in nonneoplastic tissues compared with
      neoplastic tissues. In western blotting, cancer cell lines and both nonneoplastic
      and neoplastic tissue samples showed expression of TA and DeltaN, and gamma
      isoform but beta isoform expression with or without alpha isoform was only found
      in cancer cell lines and neoplastic tissues. beta isoform, possibly of DeltaNp63,
      may be considered as an important isoform in uterine cervical squamous cell
      carcinogenesis.

PMID- 16884377
TI  - Upregulation of CD44 expression by interleukins 1, 4, and 13, transforming growth
      factor-beta1, estrogen, and progestogen in human cervical adenocarcinoma cell
      lines.
AB  - Although cervical adenocarcinoma constitutes approximately 10-20% of primary
      malignant tumors of the uterine cervix, its pathogenesis is less well understood
      than that of the corresponding squamous cancer. CD44 is a cell surface
      glycoprotein postulated to play a role in many biologic processes including tumor
      growth and metastasis. We have previously reported from immunohistochemical
      studies that a particular CD44 variant (CD44v5) is consistently overexpressed in
      endocervical neoplasia. It thus has potential as a diagnostic marker and even as
      a target for therapeutic approaches directed against specific epitopes. The aim
      of this study was to investigate which cytokines and hormones are capable of
      modulating CD44v5 expression, using a cell culture model. The effects of
      interleukin (IL)-1alpha, IL-1beta, IL-4, IL-13, transforming growth factor (TGF)
      beta1, estrogen, and progestogen on CD44v5 expression were examined in cultures
      of three human cervical adenocarcinoma cell lines (HeLa, HeLa229, and HS588T).
      Expression was assessed using dual fluorescence-labeled flow cytometry and
      western blotting techniques. It was found that incubation of cultures for 72 h
      with IL-1alpha, IL-1beta, IL-4, IL-13, TGF-beta1 (all at 0.1-10 ng/mL), estrogen
      (5-10 ng/mL), or progestogen (5-20 ng/mL) induced significant upregulation of
      CD44v5. These factors are likely to exert a similar stimulatory influence in vivo
      and may contribute to the process of carcinogenesis.

PMID- 16884379
TI  - Stage III and IV endometrial cancer: a 20-year review of patients.
AB  - In advanced endometrial cancer, the importance of peritoneal cytology and optimal
      surgical cytoreduction remain subjects of discussion. We evaluated our clinical
      experience of 67 patients with FIGO stage III and IV endometrial cancer treated
      in the Erasmus Medical Centre in Rotterdam over a 20-year period with an emphasis
      on stage IIIA disease based on positive cytology only and optimal cytoreduction.
      Lymphadenectomy was not routinely performed and peritoneal cytology was examined
      in 74% of the patients. Stage IIIA disease was found in 33 patients, 10 of whom
      had positive cytology only. Analysis showed that incidence of recurrence and
      survival rates of patients with stage IIIA disease based on positive cytology
      only were comparable with stage IIIA disease based on other factors. In 50
      patients, it was possible to remove all macroscopic tumor, whereas in 17
      patients, an optimal cytoreduction was not achievable. The 2- and 5-year survival
      rates after optimal cytoreduction were 82.2% and 65.6%; where this could not be
      achieved, these figures were 50.8% and 40.6%. In advanced endometrial cancer
      patients, positive peritoneal cytology seems an important prognostic factor in
      stage IIIA disease if lymph node status is unknown. Survival is improved if
      optimal surgical cytoreduction is achievable.

PMID- 16884380
TI  - Function of estrogen receptor isoforms alpha and beta in endometrial carcinoma
      cells.
AB  - The aim of this study was to explore how to modulate the expression of estrogen
      receptors (ER) alpha and beta and to verify the role of ERalpha and beta in
      relationship to estrogen and tamoxifen (TAM). A series of
      oligodeoxyribonucleotides (ODN) corresponding to regions of the ERalpha or beta
      was tested in human endometrial cancer cell lines (HEC-1B). The change in HEC-1B
      proliferation in response to 17beta-estradiol (E(2)) and TAM under the impact of
      antisense ODN was studied. The results of the study are as follows: 1)
      transfection with antisense ODN significantly inhibited ERalpha and ERbeta
      protein production, 2) the cells lost the ability to proliferate in response to
      E(2) after transfection with ERalpha antisense ODN especially at 24, 48, and 72
      h. There was no obvious change in response to E(2) in HEC-1B cell lines that were
      transfected with ERbeta antisense ODN, and 3) after transfection with ERalpha
      antisense ODN, HEC-1B cells lost the ability to proliferate in response to TAM at
      48 h. This inhibition was also observed after transfection with ERbeta antisense
      ODN at 24 h. ERalpha may be the primary receptor in the proliferation of HEC-1B
      cells in response to E(2). Both ERalpha and ERbeta are involved in the agonist
      impact of TAM on endometrial cancer cells.

PMID- 16884381
TI  - Mitochondrial polymorphisms as risk factors for endometrial cancer in southwest
      China.
AB  - It is just in recent years that mitochondrial DNA (mtDNA) mutations have been
      found in solid tumors. Although a direct link between the presence of mtDNA
      mutations and the development of tumors has not been made, mtDNA mutations might
      prove significant in the detection of tumor recurrence and possibly in the
      detection of genotoxic damage. To investigate the relationship between mtDNA
      variation and endometrial cancer, we collected blood samples from subjects with
      Han native background in Yunnan province in China, 49 of them with pathologically
      conformed endometrial cancer and 31 as controls with no cancer disease and
      sequenced two hypervariable segments of control region, part of 16sRNA gene,
      tRNA(leu) (tRNA is transfer RNA) gene and ND1 gene of mtDNA and identified some
      diagnostic polymorphisms by restriction fragment length polymorphism of coding
      region of mtDNA. We could not identify the suspected mutations that are related
      to diabetes and obesity from our endometrial cancer patients. However, our data
      showed that patients with endometrial cancers clustered in haplogroup D in a
      significantly higher frequency when compared with controls, implicating a
      possible association of haplogroup D to endometrial cancer. We concluded that
      mitochondrial polymorphisms in haplogroup D might play a genetic role in
      predisposing to endometrial cancer.

PMID- 16884382
TI  - Correlation of cyclin D1 and cyclin D3 overexpression with the loss of PTEN
      expression in endometrial carcinoma.
AB  - Cyclins D1 and D3 play key roles in cell cycle progression. The downregulation of
      cyclin D3 was associated with phosphatase and tensin homolog deleted on
      chromosome ten-(PTEN)-induced cell cycle arrest. We attempted to determine
      whether cyclin D1 and D3 overexpression is correlated with PTEN inactivation in
      endometrioid endometrial cancer (EEC). The expression of PTEN, cyclin D1, and
      cyclin D3 were determined by immunohistochemical analysis in 105 EEC specimens.
      Forty-three percent of the EEC demonstrated loss of PTEN expression. Cyclin D3
      was overexpressed in only 18% of the EEC specimens and was not associated with
      tumor grade. Cyclin D1 was overexpressed in 64% of the specimens and was more
      common in moderate or high-grade tumors (P = 0.002 and P = 0.02, respectively).
      The overexpression of cyclin D3 was not correlated with loss of PTEN in the EEC.
      The overexpression of cyclin D1 was much higher in grade 1 tumors with negative
      PTEN than tumors with positive PTEN expression (67% vs 26%). The overexpression
      of cyclin D3 was neither frequent nor correlated with the loss of PTEN
      expression. The overexpression of cyclin D1 was higher in the low-grade tumors
      with negative PTEN expression than tumors with positive PTEN expression.
      Overexpression of cyclin D1 is frequent in moderate or high-grade EECs and likely
      results from multiple mechanisms.

PMID- 16884383
TI  - Overexpression of cyclooxygenase-2 correlates with tumor angiogenesis in
      endometrial carcinoma.
AB  - The inducible enzyme cyclooxygenase-2 (COX-2) is an important mediator of
      angiogenesis and tumor growth. Several reports have indicated that vascular
      endothelial growth factor (VEGF)-positive tumors are associated with an increased
      amount of COX-2 protein. This study evaluated the significance of COX-2 in 34
      patients with endometrial carcinoma and its relationship to angiogenesis.
      Immunohistochemical expression of COX-2 and VEGF was analyzed on paraffin
      embedded tissue sections. Microvessel density (MVD) of endometrial carcinoma was
      also determined with anti-CD(34) as the label. COX-2 messenger RNA (mRNA) was
      analyzed by reverse transcription-polymerase chain reaction. The expression rate
      of COX-2 in 34 cases was 64.7% but not in control endometrium. COX-2 mRNA was
      higher in tumor specimens than in normal tissues. The level of COX-2 expression
      was higher in grade 2 tumors than in grade 3 tumors (P < 0.05). MVD was higher in
      COX-2-positive and VEGF-positive cases than in COX-2-negative and VEGF-negative
      cases (P < 0.05). The expression of COX-2 was positively correlated with the
      expression of VEGF and MVD (P < 0.05 and P < 0.01, respectively). The present
      findings suggest that overexpression of COX-2 may induce the expression of VEGF,
      increase angiogenesis, and enhance tumor growth.

PMID- 16884384
TI  - Expression of matrix metalloproteinase-2 and mutant p53 is increased in
      hydatidiform mole as compared with normal placenta.
AB  - Matrix metalloproteinases (MMPs) are group of enzymes thought to play an
      important role in trophoblastic and tumor invasion. The aim of our study was to
      investigate the trophoblastic expression of MMPs and p53 in normal trophoblast
      and hydatidiform moles (HM). Paraffin sections of 45 specimens, including 14
      complete hydatidiform moles (CM), 15 partial hydatidiform moles (PM), 8 atypical
      partial hydatidiform moles (aPM), and 8 controls were selected. Classification of
      HM was established on histologic criteria and supported by the DNA ploidy
      results. Tissue sections from each case were immunostained with monoclonal
      antibodies, cytokeratin-7, MMP-2, MMP-9, tissue inhibitors of metalloproteinases
      (TIMP)-1, and p53 wild type (p53wt) and mutant types (mutp53). Staining for
      cytokeratin-7 revealed a positive reaction in 93% of the samples. MMP-2 was
      mainly expressed in the syncytiotrophoblast of HM and found in 62% of aPM, 60%
      PM, and 93% CM. The mutp53 was mainly and focally expressed in
      syncytiotrophoblastic cells and was found in 63% of aPM, 80% PM, and 93% CM.
      Expression of MMP-2 and mutp53 was both significantly greater in HM vs control
      group (P < 0.05) and greater in CM vs PM and aPM (P < 0.05). No significant
      difference was observed for cytokeratin-7, MMP-9, TIMP-1, and p53wt between the
      HM subgroups and between HM and control group. MMP-2 and mutp53 are overexpressed
      in HM as compared with normal trophoblast and might participate in the invasive
      behavior of the HM.

PMID- 16884385
TI  - Integrated 18F-fluorodeoxyglucose positron emission tomography and computerized
      tomography in endodermal sinus tumor.
AB  - Application of an in-line positron emission tomography and computerized
      tomography (PET-CT) in endodermal sinus tumor (EST) is described in this study.
      CASE 1: A young female with massive ascites postovarian mass resection had
      elevated alpha-fetoprotein (AFP) serum levels. Following a positive PET-CT study
      with increased (18)F-fluorodeoxyglucose (FDG) uptake, a CT-guided core biopsy of
      a peritoneal mass was performed. EST was diagnosed histologically. The patient
      was disease free after chemotherapy. Follow-up PET-CT was negative in keeping
      with no viable tumor tissue. CASE 2: A large pelvic mass diagnosed histologically
      as primarily EST was removed in a teenage patient with elevated AFP levels. PET
      CT showed diffuse abdominal spread of FDG uptake, suggesting extensive peritoneal
      seeding. The patient was disease free after chemotherapy. Follow-up PET-CT was
      negative. EST is an FDG-avid tumor. PET-CT delineated the prechemotherapy tumor
      extent adequately ruled out the presence of residual tumor after a successful
      treatment.

PMID- 16884386
TI  - The management of an early-missed abortion after radical trachelectomy--a case
      report and a review of the literature.
AB  - Radical trachelectomy (RT) has been reported for almost 20 years. This case
      report describes and addresses the issue of the clinical management of early
      missed abortion in a patient after RT with a cerclage. CASE: A 35-year-old woman
      who had a RT 2 years ago due to cervical carcinoma stage IB1 presented with a
      missed abortion of an 8-week gestational age. At the end of the RT, a cerclage
      suture was inserted in the remaining internal oss of the cervix. The patient went
      through a cervical dilatation followed by suction curettage guided by
      ultrasonography without compromising the cerclage. This case report suggests that
      dilatation and suction curettage without compromising the cervical cerclage is a
      feasible option in the clinical management of early abortion in a patient after
      RT.

PMID- 16884387
TI  - No ancillary finding is valid to distinguish a primary ovarian hepatoid carcinoma
      from metastatic hepatocellular carcinoma.
AB  - Primary ovarian hepatoid carcinomas (POHC) are extremely rare. Especially rare
      are those with phenotypic properties of hepatocellular carcinoma (HCC) and an
      absence of clinical evidence of hepatic tumor. We report a case of a POHC with a
      common microscopic, immunophenotypic, and ultrastructural property of HCC in the
      absence of a liver mass. It is extremely difficult to differentiate POHC from
      metastatic HCC using any kinds of ancillary studies, with the exception of
      clinical identification of a hepatic tumor.

PMID- 16884388
TI  - Uterine tumor resembling ovarian sex cord tumors in a patient using tamoxifen:
      report of a case and review of literature.
AB  - Increasing number of uterine malignancies have been reported in breast cancer
      patients using tamoxifen. Most of these are endometrial adenocarcinomas. However,
      only a few cases of endometrial stromal sarcomas have been reported to be linked
      with tamoxifen usage. A 58-year-old postmenopausal women who had been using
      tamoxifen for 4 years after a surgery for breast cancer is presented with chronic
      pelvic pain. Preoperative investigations were indicative of a uterine myoma so
      that a standard total abdominal hysterectomy and bilateral salpingo-oophorectomy
      were performed. Postoperative histologic diagnosis was a uterine tumor resembling
      ovarian sex cord tumors, which is an exceedingly rare entity itself. The present
      case is the first designated diagnosis of this rare tumor, with a possible
      association of tamoxifen usage.

PMID- 16884389
TI  - Abdominal radical trachelectomy: two new surgical techniques for the conservation
      of uterine arteries.
AB  - The objective of this study was to develop two new techniques for the
      conservation of uterine arteries in abdominal radical trachelectomy. Abdominal
      trachelectomy with conservation of uterine arteries was performed in two patients
      with cervical carcinoma. In the first case, the internal iliac artery was divided
      at 2.0 cm from the bifurcation of the common iliac artery. The internal iliac
      artery and uterine artery were skeletonized along their lengths to the lateral
      cervix. The dissected internal iliac artery was then reanastomosed following the
      radical trachelectomy. In the second case, the technique was similar to that of
      the first except that the internal iliac artery was not divided. Intraoperative
      observation and postoperative color Doppler ultrasound were used to confirm the
      patency of the uterine arteries. The operative time of the two patients was 390
      min. and 350 min, respectively. Doppler flow studies demonstrated that the
      uterine arteries were patent in both cases. Resistance index of the left and the
      right uterine artery was 0.58 and 0.61, respectively, in the first case, and 0.60
      and 0.63, respectively, in the second case. Reanastomosis of the internal iliac
      arteries or skeletonization of the internal iliac arteries are both feasible
      methods to conserve the uterine arteries during abdominal radical trachelectomy.

PMID- 16884391
TI  - Laparoscopic radical trachelectomy or parametrectomy and pelvic and para-aortic
      lymphadenectomy for cervical or vaginal stump carcinoma: report of six cases.
AB  - The aim of this study was to investigate the feasibility and safety of
      laparoscopic radical parametrectomy and pelvic and para-aortic lymphadenectomy
      after previous supracervical or extrafascial hysterectomy. This is a prospective
      study of six patients with vaginal or cervical stump carcinoma after previous
      supracervical or extrafascial hysterectomy. The technique of radical
      parametrectomy with pelvic and para-aortic lymphadenectomy as used for open
      surgical cases for years was performed laparoscopically. The average operating
      time was 180 min, the estimated average blood loss was 220 mL, and the duration
      of hospitalization was 11.8 days. There was no intraoperative or postoperative
      complication. Laparoscopic radical parametrectomy with pelvic and para-aortic
      lymphadenectomy for cervical or vaginal stump carcinoma can be successfully and
      safely accomplished.

PMID- 16884390
TI  - Nerve-sparing class III radical hysterectomy: a modified technique to spare the
      pelvic autonomic nerves without compromising radicality.
AB  - The objectives were to describe our nerve-sparing class III radical hysterectomy
      technique and assess the feasibility and safety of the procedure as well as its
      impact on voiding function. From January to August 2005, 21 consecutive patients
      with FIGO stage IB-IIA cervical cancer and 1 patient with clinical stage II
      endometrial cancer underwent nerve-sparing radical hysterectomy with systematic
      pelvic lymphadenectomy. The transurethral catheter was removed on the seventh
      postoperative day. Then intermittent self-catheterization was performed and post
      void residual urine volume (PVR) was recorded. The nerve-sparing procedure was
      completed successfully and safely in all of the patients. Eight (36%) and 6 (27%)
      patients had the PVR of < 100 ml and < 50 ml respectively at the initial removal
      of the catheter. On the fourteenth day, 82% and 77% of the patients had the PVR
      of < 100 ml and < 50 ml, respectively. The mean duration before the PVR became <
      50 ml was 11.27 (5-26) days. In conclusion, the technique described in this
      preliminary study appears safe, adequate, and feasible in our population with
      satisfactory recovery of voiding function. A larger comparative study is needed
      on long-term urinary, bowel, and sexual function as well as recurrence and
      survival.

PMID- 16884393
TI  - Development of renal bone disease.
AB  - Renal osteodystrophy (ROD) develops as the early stages of chronic renal failure
      (CRF) and covers a spectrum of bone changes observed in the uraemic patient,
      which extend from high remodelling bone disease (frequently known as osteitis
      fibrosa) to low turnover, or adynamic disease. Between these two extremes there
      are also cases of bone mineralization compromised in variable degrees, as is the
      case of 'mixed bone disease' and osteomalacia. The dynamic process of bone
      remodelling is compromised in CRF, and a positive or negative bone balance can be
      observed in uraemic patients. In addition to the classic modulators of bone
      remodelling, like parathyroid hormone, calcitriol and calcitonin, other factors
      were recently identified as significant modulators of osteoblast and osteoclast
      activation in uraemic patients. In fact, different cytokines and growth factors,
      acting at an autocrine or paracrine level, seem to play a relevant role in the
      bone and mineral changes observed in uraemia. Recently, observations have been
      made of the development of more sensitive and specific techniques to assay
      different biochemical markers of bone turnover and mineral metabolism.
      Analogously, new contributions of conventional bone histology, bone
      immunocytochemistry and molecular biology, which enabled the understanding of
      some etiopathogenic mechanisms of ROD, were observed.

PMID- 16884394
TI  - Diagnosis of renal osteodystrophy.
AB  - The idiom renal osteodystrophy (ROD) represents a heterogeneous pattern of bone
      disturbances caused by chronic renal insufficiency and concomitant diseases. For
      the clinical decision of therapy it is most important to differentiate between
      high and low or adynamic turnover ROD because the therapeutically consequences of
      these two ends of the ROD spectrum are fundamentally different. Bone histology
      remains the gold standard for the exact classification of ROD. Serological
      markers of bone metabolism are not suited for the accurate nomenclature of ROD
      but are useful for the sequential follow up of ROD after a clear diagnosis has
      been made. Similarly, radiological diagnosis of ROD using dual energy X-ray
      absorptiometry (DEXA) or quantitative computer tomography scan (q-CT) is
      inaccurate and thus more suited for the routine follow up of established disease.
      Besides mineralization, bone strength and the rate of fractures are strongly
      determined by the architecture of the bone matrix. This information, however, is
      also only available on bone biopsy sections and cannot be estimated by non
      invasive diagnostic methods. In summary, bone biopsy should be used more
      liberally for correct classification of bone disease. The sequential follow up
      and guidance of therapy success can be performed by non-invasive procedures such
      as biochemical bone marker determination in blood. X-ray imaging and densitometry
      is suitable only for sequential evaluation of osteoporosis.

PMID- 16884395
TI  - Influence of the parathyroid glands on bone metabolism.
AB  - Bone is a classic target tissue for parathyroid hormone (PTH), whose calciotropic
      effect is mediated largely via catabolic actions on this tissue. Paradoxically,
      PTH also exerts anabolic actions, with intermittent injections of PTH or its
      amino-terminal fragments causing an increase in bone formation and bone mass,
      actions that form the basis for the use of PTH in the treatment of osteoporosis.
      Besides vitamin D, PTH is the only other known bone anabolic agent. High-affinity
      PTH receptors (PTH-1R) have been detected on osteoblasts and osteoclasts (albeit
      in lower numbers). Bone turnover, which includes activation of osteoclasts and
      osteoblasts, appears to be best reflected not by absolute concentrations of PTH
      (which can vary based on the assay and antibody used) but by a balance of
      circulating full-length PTH-(1-84) and amino-terminally truncated C-PTH
      fragments. When PTH-(1-84) is predominant, bone turnover is promoted. Among PTH
      fragments, PTH-(7-84) appears to be the most potent antagonist of PTH-(1-84). The
      mechanisms involved in these effects are unclear although mediation via unique C
      terminal receptors has been suggested. We propose that, within the range of total
      PTH (100-1000 pg mL(-1)), the ratio of PTH-(1-84)/C-PTH fragment is a valuable
      tool for diagnosis of bone turnover. Data indicate that at PTH levels < 100-150
      pg mL(-1) and > 1000 pg mL(-1), the ratio looses its predictive power. Assay
      type, patient characteristics (race, underlying renal disease) and treatment
      attributes (vitamin D, corticosteroids, phosphate binders) have an impact on the
      PTH ratio, and care should be used in interpreting assay results and making
      subsequent treatment decisions.

PMID- 16884396
TI  - Emerging role of a phosphatonin in mineral homeostasis and its derangements.
AB  - BACKGROUND: The study of a distinct group of renal phosphate wasting disorders
      with bone disease which comprise X-linked hypophosphatemic rickets (XLH),
      autosomal dominant hypophosphatemic rickets (ADHR) and tumour-induced
      osteomalacia (TIO) gave rise to the identification of different hormone-like
      peptides, also known as phosphatonins. These factors are responsible for the
      major disease features that characterize XLH, ADHR and TIO. Recent reports on one
      of these phosphatonins, fibroblast growth factor-23 (FGF-23), point to a general
      role of this factor in mineral ion metabolism. OBJECTIVES: The main focus regards
      recent evidence implicating FGF-23 in normal and disordered mineral homeostasis
      with special emphasis on chronic kidney disease. The interactions of FGF-23 with
      phosphate, parathyroid hormone and vitamin D are discussed in detail. SUMMARY:
      The FGF-23 has been shown to increase urinary phosphate excretion, inhibit bone
      mineralization and suppress 1,25-dihydroxy vitamin D(3)[1,25(OH)(2)D(3)], the
      main characteristics that XLH, ADHR and TIO have in common. Apart from its role
      in these phosphate wasting disorders serum FGF-23 is elevated in
      hypoparathyroidism and humoral hypercalcaemia of malignancy and responds to
      altered dietary phosphate and calcium supply in healthy subjects. The FGF-23 is
      also variably elevated in chronic kidney disease and associated secondary
      hyperparathyroidism where it correlates positively with serum phosphate and
      parathyroid hormone and negatively with 1,25(OH)(2)D(3). Such relationships,
      along with data from experimental studies, raise the question of whether FGF-23
      contributes to the pathophysiology of chronic kidney disease.

PMID- 16884397
TI  - Function and effect of bone morphogenetic protein-7 in kidney bone and the bone
      vascular links in chronic kidney disease.
AB  - In two independent and separate studies, we have shown that renal injury and
      chronic kidney disease (CKD) directly inhibit skeletal anabolism, and that
      stimulation of bone formation decreased the serum phosphate. In the first study,
      the serum Ca PO(4), parathyroid hormone (PTH), and calcitriol were maintained
      normal after renal ablation in mice, and even mild renal injury equivalent to
      stage 3 CKD decreased bone formation rates. More recently, these observations
      were rediscovered in low-density lipoprotein receptor null (LDLR-/-) mice fed
      high-fat/cholesterol diets, a model of the metabolic syndrome (hypertension,
      obesity, dyslipidemia and insulin resistance). We demonstrated that these mice
      have vascular calcification (VC) of both the intimal atherosclerotic type and
      medial calcification. We have also shown that VC is made worse by CKD and
      ameliorated by bone morphogenetic protein-7 (BMP-7). The finding that high-fat
      fed LDLR-/- animals with CKD had hyperphosphatemia which was prevented in BMP-7
      treated animals lead us to examine the skeletons of these mice. It was found that
      significant reductions in bone formation rates were associated with high-fat
      feeding, and superimposing CKD resulted in the adynamic bone disorder (ABD),
      while VC was made worse. The effect of CKD to decrease skeletal anabolism
      (decreased bone formation rates and reduced number of bone modelling units)
      occurred despite secondary hyperparathyroidism. The BMP-7 treatment corrected the
      ABD and hyperphosphatemia, owing to BMP-7-driven stimulation of skeletal
      phosphate deposition reducing plasma phosphate and thereby removing a major
      stimulus to VC. A pathological link between abnormal bone mineralization and VC
      through the serum phosphorus was demonstrated by the partial effectiveness of
      directly reducing the serum phosphate by a phosphate binder that had no skeletal
      action. Thus, in the metabolic syndrome with CKD, a reduction in bone forming
      potential of osteogenic cells leads to the ABD producing hyperphosphatemia and
      VC, processes ameliorated by BMP-7, in part through increased bone formation and
      skeletal deposition of phosphate and in part through direct actions on vascular
      smooth muscle cells. We have demonstrated that the processes leading to vascular
      calcification begin with even mild levels of renal injury affecting the skeleton
      before demonstrable hyperphosphatemia and that they are preventable and
      treatable. Therefore, early intervention in the skeletal disorder associated with
      CKD is warranted and may affect mortality of the disease.

PMID- 16884398
TI  - Vascular calcification and renal osteodystrophy relationship in chronic kidney
      disease.
AB  - Cardiovascular disease and stroke account for 60-70% of all deaths in patients
      with end-stage renal disease (ESRD), at a risk that is 10-20-fold the age- and
      sex-matched general population. There is also increased coronary artery
      calcification and increased cardiovascular mortality in chronic kidney disease
      (CKD) and dialysis patients compared with the general population. Bone is
      similarly abnormal in CKD. There is an increased incidence of low bone mass and
      fractures in dialysis patients compared with the general population. Furthermore,
      a hip fracture in a dialysis patient is associated with a doubling of the
      mortality observed in nondialysis patients with a hip fracture. These two
      problems may be linked, as cross-sectional studies have demonstrated an inverse
      relationship between osteoporosis and coronary artery calcification in the
      general population and in ESRD patients. In vitro and ex vivo, there is clear
      evidence that vascular calcification is an active cell-mediated process, made
      worse by disorders of mineral metabolism. Many factors known to be associated
      with cardiovascular disease in CKD patients can directly increase calcification
      in vitro. In addition, in CKD, there are many mechanisms by which bone may
      adversely affect vascular calcification including disorders of bone remodelling,
      altered secretion of parathyroid hormone (PTH), hyperphosphatemia,
      hypercalcaemia, use of calcium based binders, and excessive vitamin D therapy.
      The coexistence of vascular risk factors and abnormal bone represent a double
      threat to the well being of patients with CKD.

PMID- 16884399
TI  - Effect of kidney transplantation on bone.
AB  - A broad range of different factors aggravates renal osteodystrophy, which is
      present in virtually all patients with chronic kidney disease and after
      successful kidney transplantation. Altered hormonal status, including sex
      hormones and parathyroid hormone (PTH), a deficit of 1,25(OH)(2) vitamin D(3)
      (calcitriol), immunosuppressive therapy and post-operative immobilization
      contribute to a progressive loss of bone density and structure. The decrease of
      bone mass is particularly prominent during the first 6 months after kidney
      transplantation and is associated with an increased number of fractures, both
      compared with the normal population as well as with dialysis patients. At
      particular risk are patients with a history of diabetes, long duration of
      haemodialysis and post-menopausal women. To prevent post-transplant bone loss
      prescription of steroids should be minimized and withdrawn as early as possible.
      Additional intake of alpha-calcidol [25(OH) vitamin D(3)] or calcitriol, despite
      normal serum levels, reduces persistent hyperparathyroidism after kidney
      transplantation, improves intestinal calcium absorption and activates
      osteoblasts. Inhibition of osteoclasts by biphosphonate therapy seems to
      effectively reverse bone loss during the early and late course of kidney
      transplantation. However, as the majority of transplant recipients have a low
      turnover bone disease, inhibition of osteoclasts, through which bone turnover is
      impaired, might further reduce osteoblast activity and promote osteoid synthesis.
      Most investigations were small-scale studies with 10-100 participants and a
      follow up of only 12 months. This makes conclusions on the effect of any
      intervention on the fracture rate impossible. Larger, randomized multicentre
      studies investigating bone-sparing therapy on hard end points are therefore
      advocated.

PMID- 16884401
TI  - Application of insect repellents by travelers to malaria endemic areas.
AB  - The use of insect repellents applied to the skin is always encouraged in those
      visiting malaria endemic areas. There are a number of factors contributing to the
      efficacy of insect repellents in the field and an important factor contributing
      to their longevity relates to the applied dose. This study investigated the dose
      of insect repellent that travelers might normally apply to the skin. Subjects
      were asked to apply a product they had purchased to the arms and neck, and the
      dose applied (mg/cm(2)) was calculated. The study was conducted using three
      different populations; 74 travelers to malaria endemic areas visiting pharmacies
      to purchase repellents before they left the UK, 23 travelers on safari in India,
      and 24 on safari in Kenya. There was a significant difference in the mean applied
      arm dose of product (mg/cm(2)) [p < 0.001, analysis of variance (ANOVA)]; UK 1.15
      (SD 0.29), India 0.96 (SD 0.23), and Kenya 1.34 (SD 0.54). Higher concentrations
      were achieved on the neck area. Few of the participants in the field trial used
      long-sleeved shirts at night. Even using 50% wt/vol repellent products, 32% in
      the Kenya and 25% in the India, study achieved a dose of active ingredient less
      than 0.5 mg/cm(2). These pilot studies would indicate that travelers tend to
      apply below the optimal concentration of active ingredient of repellent as might
      be suggested by mathematical models.

PMID- 16884400
TI  - Infectious mononucleosis-like syndromes in febrile travelers returning from the
      tropics.
AB  - Infectious mononucleosis (IM), resulting from Epstein-Barr virus (EBV) infection,
      and IM-like syndromes, mainly due to cytomegalovirus (CMV), Toxoplasma gondii, or
      human immunodeficiency virus (HIV), have been occasionally reported in travelers
      returning from the tropics. Our objective was to investigate the prevalence,
      outcome, and diagnostic predictors of these syndromes in febrile travelers.
      Between April 2000 and March 2005, all febrile travelers and migrants presenting
      at our referral centers within 12 months after a tropical stay were prospectively
      included. We identified all patients serologically diagnosed with IM or IM-like
      syndrome and compared them with the rest of the cohort. During the 5-year period,
      72/1,842 patients (4%) were diagnosed with an IM-like syndrome, including 36 CMV,
      16 T gondii, 15 EBV, and 5 HIV primary infections. All patients were western
      travelers or expatriates. Mean delay before consultation was 2 weeks. Most
      patients had consulted other practitioners and/or received presumptive treatment.
      A minority of patients presented with IM clinical features. Lymphocytosis > or
      =40% of the white blood cells (WBC) and reactive/atypical lymphocyte morphology
      were observed in 60 and 30% of the patients. The four diseases were
      indistinguishable. Protracted fever and asthenia were common but complications
      rarely occurred. IM-like syndromes were independently associated with fever >7
      days, lymphadenopathy, elevated liver enzymes, and lymphocytosis > or =40% of
      WBC. Diagnostic probability increased to >20% if at least three of these
      predictors were present. Diagnosis of IM and IM-like syndrome is not uncommon in
      febrile travelers, with a higher proportion of primary CMV, T gondii, and HIV
      infections than in nonimported series. Consequently, classic IM clinical and
      laboratory features are often lacking. All four pathogens should be
      systematically considered because early diagnosis should avoid unnecessary
      investigations and treatment and allow early intervention in case of primary HIV
      infection.

PMID- 16884402
TI  - Diarrhea and respiratory symptoms among travelers to Asia, Africa, and South and
      Central America from Scotland.
AB  - Surveillance using admissions to hospital, while being useful, is a poor
      indicator of the real incidence of disease encountered by travelers. An
      alternative is self-reported illness among those who attended at a pretravel
      clinic prior to their travels. Estimates of incidence and risk factors were
      determined for attendees at a travel clinic in Scotland using a questionnaire.
      Analysis for risk factors was carried out for those travelers visiting countries
      in Africa, Asia, or South and Central America, who had traveled for 1 week or
      more and had returned between 1997 and 2001 (N= 4,856). Multivariate logistic
      regression was used to test the hypotheses that time abroad and age-group would
      be significant for both respiratory and diarrheal symptoms regardless of which of
      the three geographical areas are visited. From 2006 returned questionnaires
      (response rate = 41.3%), diarrhea and respiratory symptoms were reported by 44.2
      and 16.8% of respondents, respectively; the incidence was significantly greater
      among travelers to Asia for both diarrheal (55.5%) and respiratory (23.7%)
      symptoms than among travelers to Africa (36.6 and 12.2%, respectively) or South
      and Central America (39.5 and 16.2%, respectively). For diarrhea, age was a
      highly significant risk factor for travelers to Asia, South and Central America,
      and Africa. Being a self-organized tourist/backpacker, traveling to Asia was
      associated with increased risk, while for Africa and South and Central America
      visiting family or friends was associated with a lower risk. For travelers to
      Asia, traveling to the Indian subcontinent was significantly associated with
      increased risk. The majority of travelers had an adverse event while traveling
      abroad, with diarrhea and respiratory conditions being especially common despite
      attending a travel clinic for advice prior to departure. However, the limitations
      of this surveillance-based strategy have highlighted the requirement for more
      research to understand more fully the issues of risk and incidence among
      travelers to high-risk destinations from Scotland.

PMID- 16884403
TI  - Immunity to hepatitis A and hepatitis B in Indian and Chinese immigrants seen in
      a travel clinic in Massachusetts, United States.
AB  - Immigrants to the United States from developing countries have a higher
      probability of previous infection with hepatitis A virus (HAV) and/or hepatitis B
      virus in their countries of origin. Prior knowledge of hepatitis A and B
      seroprevalence in this population may aid in determining the need for pretravel
      immunizations when these individuals travel to endemic regions. We conducted a
      retrospective analysis of hepatitis A and B serologies in a travel clinic
      population (from March 1999 through September 2002) to determine the
      seroprevalence in our predominantly highly educated foreign-born subjects. All
      our patients who had immigrated from China and India and who were older than 60
      years (born on or before 1940) were immune to hepatitis A. The Indian and Chinese
      subjects who were anti-HAV positive were also significantly older than the anti
      HAV negative group. In addition, in our Indian study group, the hepatitis A
      seropositive individuals first left India at a significantly older age than the
      hepatitis A-seronegative group (mean age 22.7 years vs 11.4 years, p < 0.05). Our
      small sample size of Chinese subjects may not have permitted a statistically
      significant difference to be detected for hepatitis A seroprevalence and age at
      departure from their country of origin. These results have helped tailor our
      recommendations for pretravel immunizations for our groups of foreign-born
      individuals planning to visit endemic areas. Individuals born in China or India
      on or before 1940 are likely to have preexisting antibody to hepatitis A and
      probably do not need the vaccine when they travel. Younger individuals may elect
      to have a hepatitis A antibody titer checked before getting the vaccine.

PMID- 16884404
TI  - Hepatitis A, typhoid and malaria among travelers--surveillance data from Quebec
      (Canada).
AB  - Analysis of epidemiological data on health problems related to international
      travel helps put into perspective preventive interventions for travelers. To
      document the epidemiological context of travel health interventions in Quebec, we
      reviewed surveillance data for three infectious diseases. The analysis included
      data collected in the notifiable diseases surveillance system for hepatitis A,
      typhoid, and malaria cases reported from 2000 to 2002. Additional data were
      obtained from the provincial hepatitis risk factor database as well as from
      regional public health departments. More than 40% of cases of hepatitis A for
      which risk factor information is available are associated with international
      travel; 20% of these cases were contracted in Mexico and 22% in the West Indies.
      The risk of acquiring hepatitis A seems to be higher among travelers under 35
      years of age; also, given the number of Quebecers traveling to all regions of the
      world, this risk is proportionally higher in Africa. Data gathered for typhoid
      indicate that the risk to travelers from Quebec is proportionately higher for
      Quebecers traveling to the Indian subcontinent and whose purpose is to visit
      family and friends, and for those who stay abroad for 4 weeks or longer. The risk
      of malaria is greater in Africa (where contracted cases are mostly caused by
      Plasmodium falciparum). Over half of malaria cases involve individuals traveling
      abroad for business (including volunteerism), and almost 75% contracted the
      disease during a stay of a month or more. Nearly half of the cases had not taken
      chemoprophylaxis. Available data have limitations for infectious disease
      surveillance among Quebec travelers: imprecise number of cases (underdiagnosis
      and underreporting), imprecise denominators (number of travelers), and lack of
      data on the characteristics of trips taken. However, despite its limitations,
      this profile of infectious diseases among travelers from Quebec provides
      interesting data for preventive intervention.

PMID- 16884405
TI  - Travel clinics in Quebec (Canada).
AB  - To continuously improve its assistance to Quebec travel health providers, the
      Quebec Advisory Committee on Travel Health conducted an exploratory and
      descriptive survey of dedicated travel clinics in Quebec (Canada). During autumn
      2003, a cross-sectional descriptive survey was carried out among the 97 travel
      health clinics listed in Quebec. Data were collected using a self-administered
      questionnaire sent by mail. The response rate was 94%. More than three quarters
      of travel clinics in Quebec are located in community health centers; the others
      are in private clinics and in hospitals. Although 80% of the clinics are located
      outside the most densely inhabited regions of Quebec, they carry out less than
      30% of the total number of pretravel consultations. Almost 60% of the clinics
      have fewer than 500 consultations a year. Overall, more than 114,000 travel
      health consultations are performed annually in Quebec travel health clinics.
      Preventive services to travelers, including the most commonly used vaccines for
      travelers, are available in all regions of Quebec, except in the northernmost
      region. Smaller clinics offer fewer services to travelers in terms of
      antimalarial prescriptions, less common vaccines, and post-travel consultations.
      The main sources of information for travel health practitioners are guidelines
      provided by public health authorities. Data obtained provide an up-to-date
      portrait of the services available in travel clinics in Quebec that should assist
      public health authorities adapt their interventions to the needs and realities of
      these clinics.

PMID- 16884407
TI  - A probable case of Irukandji syndrome in Thailand.
AB  - The Irukandji syndrome is a jellyfish envenomation caused by Carukia barnesi or
      related jellyfish. In literature, the distribution of "Irukandji-like" syndromes
      is restricted to Australia. We report a case of probable Irukandji syndrome in
      Thailand. With this report, we hope to promote awareness to aid sting prevention
      and stimulate research.

PMID- 16884406
TI  - Undiagnosed and potentially lethal parasite infections among immigrants and
      refugees in Australia.
AB  - Intestinal parasite infections are a major cause of ill health in many resource
      poor countries. This study compares the types and rates of these infections and
      their risk factors in recently arrived and long-term immigrants in Australia.
      Cross-sectional surveys of 127 East African and 234 Cambodian immigrants and
      refugees were undertaken in 2000 and 2002, respectively, to assess the burden of
      intestinal parasites and collect demographic information. Serum samples were
      assessed for eosinophilia and Strongyloides stercoralis and Schistosoma
      antibodies, and feces examined for ova, cysts, and parasites. Intestinal
      parasites were identified in 77/117 fecal samples from East African and in 25/204
      samples collected from Cambodian participants. Eleven percent (14/124) of East
      Africans and 42% (97/230) of Cambodians had positive or equivocal serology for S
      stercoralis. Schistosoma serology was positive or equivocal in 15% (19/124) of
      East African participants. Potentially serious intestinal parasite infections are
      common among recent and longer term immigrants despite multiple visits to health
      care providers. Immigrants and refugees from high-risk countries would benefit
      from comprehensive health checks soon after resettlement.

PMID- 16884410
TI  - The function of metered dose inhalers at moderate altitude.

PMID- 16884408
TI  - Extensive cutaneous larva migrans with folliculitis mimicking multimetameric
      herpes zoster presentation in an adult traveler returning from Thailand.
AB  - Hookworm-related cutaneous larva migrans (CLM) is a frequent cutaneous disease
      among travelers returning from the tropics. It can be misdiagnosed or treated
      incorrectly. We present a 42-year-old French patient who contracted the disease
      during a holiday in Thailand and who experienced an extensive CLM syndrome with a
      less frequent abdominal localization and a pseudo-multimetameric homolateral
      topography. The condition was late diagnosed and secondarily efficiently cured by
      a unique administration of ivermectin. Simple anamnestic information--often
      revealing beach activities--and clinical aspect of the creeping eruption allow to
      prevent diagnosis delay and to avoid aggressive or inadequate intervention.

PMID- 16884412
TI  - Small bowel CT-enteroclysis: technique, pitfalls and pictorial review.
AB  - Computed tomography small bowel enteroclysis has been carried out at Noosa
      Hospital since July 2003, and more recently at St George Private Hospital,
      Kogarah. Over 125 cases have been carried out. This article describes the
      different techniques, the pitfalls and a pictorial review of small bowel
      pathology.

PMID- 16884413
TI  - CT appearances of hydatid disease at various locations.
AB  - Hydatid disease has characteristic imaging features on CT, which allow accurate
      preoperative diagnosis in most cases. However, when it occurs at unusual
      locations the diagnosis is often difficult, especially as the imaging appearance
      varies at different sites. In this article we have presented a pictorial review
      of the CT features of disease due to Echinococcus granulosus at various sites in
      the human body.

PMID- 16884414
TI  - Medial meniscus posterior root attachment injury and degeneration: MRI findings.
AB  - The posterior root attachment of the medial meniscus is readily identifiable on
      MRI. Unless specifically reviewed, injuries involving this structure may be
      overlooked. Significant meniscal root pathology may cause functional incompetence
      of the meniscus, with consequent early onset cartilage degeneration and
      osteoarthritis. This review article emphasizes the importance of positive
      identification of an intact meniscal root and illustrates the known association
      of meniscal root injury or tear with medial extrusion of the medial meniscus by
      greater than 3 mm beyond the joint margin.

PMID- 16884415
TI  - Anatomical variations of the internal jugular veins and their relationship to the
      carotid arteries: a CT evaluation.
AB  - The right internal jugular vein (IJV) is a common vessel to obtain venous access.
      It is important to have a clear understanding of the anatomy of the IJV and its
      relationship to the common carotid arteries (CCA) to avoid inadvertent arterial
      puncture. This study aims to objectively evaluate the variations in the anatomy
      of IJV and its relation to the CCA. A total of 176 right and left IJV were
      retrospectively evaluated using CT imaging with the CentraRad Diagnostic Viewer
      Version 4.09.0190 (CDN Telemedicine Solutions, Wollongong, Australia). The data
      were recorded and analysed. The right IJV (80.5%) was more often larger than the
      left IJV. With reference to the CCA, 85.2% of the IJV were found in the lateral
      position, 12.5% anteriorly, 1.1% medially and 1.1% posteriorly. Seven IJV were
      found to be hypoplastic, and in one case this was seen bilaterally in both the
      right and left IJV. The maximum depth of IJV from the skin was 27.9 mm. More than
      half (69.5%) of the IJV were less than 1 mm from the carotids. Computed
      tomography is an excellent method to delineate the anatomy of IJV. Variations in
      the anatomy of the IJV and their correlation to the CCA are common.

PMID- 16884416
TI  - Practice MRI: reducing the need for sedation and general anaesthesia in children
      undergoing MRI.
AB  - The aim of this study was to evaluate the effectiveness of a practice magnetic
      resonance unit, in preparing children to undergo magnetic resonance procedures
      without general anaesthesia (GA) or sedation. The records of children who
      attended the practice MRI between February 2002 and April 2004 were
      retrospectively reviewed. Each record was assessed as to whether the child had
      passed or failed the practice MRI intervention. Those children who were
      considered to have passed and were proceeded to a clinical non-GA MRI had the
      report of the clinical scan reviewed. If the scan had been reported as non
      diagnostic because of movement artefact it was classified as a failed scan,
      otherwise it was considered a pass. One hundred and thirty-four children
      undertook a practice MRI (age range 4.1-16.1 years, median age 7.7 years, 47%
      boys) and 120/134 (90%) passed the practice session. In all, 117/120 (98%)
      subsequently had a clinical non-GA MRI and 110/117 (94%) passed (median age 7.8
      years, 47% boys). Preparation is a safe and effective method to reduce the need
      for sedation and GA in children undergoing a clinical MRI scan. It provides a
      positive medical experience for children, parents and staff, and results in cost
      savings for the hospital.

PMID- 16884417
TI  - A new look into kicking a football: an investigation of muscle activity using
      MRI.
AB  - The kicking action predominantly used in Australian Rules football is considered
      to be responsible for many lower limb injuries. The aim of this study was to
      describe a non-invasive method of identifying the thigh muscles involved in
      kicking an Australian Rules football, using MRI. Both upper thighs of 10
      recreational footballers were examined using a 1.5-T General Electric MRI scanner
      before and immediately after carrying out a set kicking exercise protocol. The
      signal intensity (SI) changes in 14 individual muscles were investigated using a
      standardized region of interest to determine the levels of muscle activity.
      Significant SI changes were observed in several muscles of the kicking and stance
      legs among all participants. In the kicking leg, the greatest SI changes were
      observed in the adductor longus and tensor fascia latae muscles (49.38% (+/-8.95)
      and 45.47% (+/-7.91), respectively; P < 0.05), whereas in the stance leg, the
      muscles displaying the highest changes were the semitendinosus and tensor fascia
      latae muscles (46.48% (+/-9.97) and 33.68% (+/-8.36), respectively; P < 0.05).
      This study has shown that MRI can be useful for observing the activity of
      individual muscles in the upper thigh during the kicking motion. This non
      invasive approach provides a detailed analysis of anatomy and emphasizes the
      muscles at high risk of injury.

PMID- 16884418
TI  - Primary sclerosing cholangitis: correlation of hepatobiliary scintigraphy with
      clinical and laboratory status.
AB  - The aim of this study was to determine whether hepatobiliary scintigraphy using
      (99m)technetium based di-isopropryl-imino-diacetic acid correlated to clinical or
      laboratory status of patients with primary sclerosing cholangitis (PSC). We
      carried out a retrospective case-control study involving 15 patients with proven
      PSC. Fifty-seven hepatobiliary scintigraphic studies were reviewed by consensus
      of two experienced observers using a semiquantitative scheme to score liver size
      and degree of radiopharmaceutical uptake, intrahepatic or extrahepatic biliary
      stasis, segmental liver clearance half-times and gall bladder visualization. The
      results were compared with age; disease duration; weight loss; serum bilirubin,
      alkaline phosphatase and albumin levels; antipyrine clearance; number of biliary
      stents and episodes of cholangitis and history of transplantation. Sixteen age
      matched and sex-matched individuals with PSC, who did not undergo hepatobiliary
      scans, were selected for comparison. Among the scintigraphic variables, right
      lateral and superior liver clearance half-time values showed a significant linear
      correlation with disease duration and serum alkaline phosphatase levels (P <
      0.05) but not with other clinical or biochemical indices. Other scintigraphic
      variables showed no correlation. An abnormal, hepatobiliary scan liver clearance
      half-time in patients with PSC correlates to disease duration and increased serum
      alkaline phosphatase levels, and this variable may be used to identify some
      subjects with more advanced disease.

PMID- 16884419
TI  - Stratification of radiological test ordering: its usefulness in reducing
      unnecessary tests with consequential reduction in costs.
AB  - This study examines the effectiveness of an automated, stratified system of
      radiological test ordering, known as 'Traffic Lights', in reducing the number of
      unnecessary tests and their associated costs. The system involves stratification
      of radiological tests into three groups, denoted by red, amber and green colours.
      'Red' tests must be authorized by a consultant. 'Amber' tests must be signed by a
      registrar or authorized by a consultant. 'Green' tests can be ordered directly by
      residents or interns. In the 4 months after the introduction of 'Traffic Lights',
      each radiological method showed a reduction in both the number of tests and their
      associated costs. The reduction was consistent across both medical and surgical
      groups. Analysis of data 20 months immediately after the introduction of 'Traffic
      Lights' also showed a consistent reduction in the total number of tests,
      suggesting that the changes are sustainable and unlikely to be due to seasonal
      variation. Combined with evidence-based medicine protocols, this stratified
      system of radiological test ordering should ensure the safety, quality and
      appropriateness of imaging tests and minimize overall patient radiation dose.

PMID- 16884420
TI  - Problem-based learning: concept, theories, effectiveness and application to
      radiology teaching.
AB  - Australian and New Zealand medical schools are partly or entirely incorporating
      problem-based learning (PBL) in their medical school curricula. As this change
      moves forwards and gathers momentum, radiologists are called upon to facilitate
      or to contribute to PBL tutorials. This study explains the concept and the
      theories of PBL and discusses its application to radiology teaching.

PMID- 16884422
TI  - Development of a clinical chart audit programme.
AB  - Radiation oncology charts containing medical information and treatment details
      are the major methods of communication between the various personnel involved in
      delivering radiation therapy to the patient. It is paramount to good patient care
      for this communication to be clear, precise and accurate in detail. A regular
      chart audit should be a part of the quality assurance programme of every
      radiation oncology department. The primary aim of this study was to develop and
      assess an objective and quantitative programme for reviewing radiation oncology
      charts, thereby improving the quality of communication and hence patient
      management. A secondary aim was to compare the charts of radically treated
      patients with those treated palliatively. A pilot study using a new chart review
      tool, developed at the Perth Radiation Oncology Centre, was carried out over an 8
      month period. A sample of charts, representing 25% of our treatment group, were
      assessed using the tool on a monthly basis. A total of 156 charts were reviewed
      during this time period. Fifty-six per cent were radical treatments and 44% were
      palliative. The overall mean chart scores significantly improved over the time of
      this study (P < 0.001). The individual radiation oncologists' scores were also
      seen to improve during the study period. The alpha coefficients for intra-rater
      and inter-rater reliability were 0.99 and 0.88, respectively. The chart review
      programme was found to be an easy-to-use and a reliable tool by both medical and
      non-medical reviewers. It appeared to have a positive influence on the standard
      of radiation oncology charts in our department.

PMID- 16884421
TI  - Concurrent end-phase boost high-dose radiation therapy for non-small-cell lung
      cancer with or without cisplatin chemotherapy.
AB  - The aim of this study was to audit the results of a high-dose, combined-modality
      prospective protocol for non-small-cell lung cancer in terms of survival, disease
      specific survival and toxicity. One hundred and twenty-one patients with non
      small-cell lung cancer were treated with a concurrent, end-phase, boost, high
      dose radiotherapy protocol with 65 Gy in 35 fractions for more than 5 weeks.
      Sixty-six patients received radiotherapy alone (group 1), 29 received concurrent
      chemoradiation (group 2) and 26 received neoadjuvant and concurrent chemotherapy
      (group 3). Thirty-four patients had stage I disease, six had stage II and 81 had
      stage III. Overall median survival was 23 months: 75% at 1 year and 23% at 5
      years. Median survivals for patients with stage I and stages II and III disease
      were 43 and 19 months, respectively. For stages II and III patients by groups 1
      3, median survivals were 18, 25 and 18 months, respectively, and 2-year survivals
      were 36, 52 and 38%, respectively. Toxicity was acceptable. Overall, 9% had
      symptomatic pneumonitis and 7% had grades 3 and 4 oesophagitis. For those who had
      the mediastinum included in the volume, grade > or = 3 oesophagitis occurred in
      0, 11 and 22% (n = 110, P = 0.001), respectively, for treatment groups 1-3.
      Overall treatment-related mortality was 3%, consisting of two septic deaths, one
      pneumonitis and possibly one late cardiac event, all occurring in patients who
      had chemotherapy (7% of 55 patients). Treatment-related mortality declined over
      the study period. Accelerated radiotherapy was well tolerated, with only moderate
      increased acute toxicity when combined with concurrent platinum chemotherapy.
      Toxicity was enhanced by induction chemotherapy. Overall survival outcomes were
      excellent for this condition. Continued use of this radiotherapy schedule is
      recommended as the platform for assessment of other chemotherapy schedules.

PMID- 16884423
TI  - Assessment of abstracts submitted to the annual scientific meeting of the Royal
      Australian and New Zealand College of Radiologists.
AB  - The process for selecting abstracts submitted for presentation at annual
      scientific meetings should ensure both the quality of these meetings and fairness
      to prospective presenters. The aim of the present study was to review the
      assessment of radiation oncology abstracts submitted for oral presentation to the
      2004 Royal Australian and New Zealand College of Radiologists annual scientific
      meeting. Selection criteria were developed that were primarily focused on the
      subjective aspects of abstract quality. All research abstracts were reviewed
      blindly by five individual reviewers (four radiation oncologists and a
      statistician), scoring each abstract in five categories. The scores of three
      reviewers were used to select the top 30 general and top eight trainee entries.
      For comparison, cluster analysis using the scores of all five reviewers was used
      to group papers into two ranks. There was a strong correlation in total scores
      for each paper, between all reviewers. Similarly, the study design subscale was
      strongly correlated between all reviewers. Abstracts belonging to the first-rank
      cluster were generally selected. Most trainee entries would have been successful
      in being accepted into the general programme. The selection process described
      appears feasible and fair and may improve the quality of meetings.

PMID- 16884424
TI  - Childhood glioblastoma multiforme of the spinal cord.
AB  - Astrocytoma accounts for more than 50% of all central nervous system tumours
      diagnosed, with particular prevalence in the 15- to 34-year-old age bracket,
      rarely arising in younger children. In 1995, a 7-year-old boy presented in
      Emergency with a 3-day history of severe radicular back pain and associated
      muscle spasms, exacerbated by lying on his back. Both bone scan and plain X-rays
      were unremarkable; however, MRI showed a 3-cm space-occupying lesion at the level
      of T5-T6. The patient proceeded to biopsy and partial excision of the tumour
      through laminectomy, histology confirming an anaplastic astrocytoma (glioblastoma
      multiforme), St Anne Mayo grade 4. Treatment consisted of a radical course of
      radiotherapy alone, delivering a total dose of 44.8 Gy at 1.6 Gy per fraction.
      The treatment comprised of three phases using two oblique wedged fields on a 6 MV
      linear accelerator. The patient remains disease free 7 years post treatment, with
      the only effect noted being a slight kyphoscoliosis at the site of the
      laminectomy and radiation. This report highlights the efficacy of combined
      surgery and radiation therapy in the management of spinal cord glioblastoma
      multiforme in preventing tumour recurrence, with acceptable morbidity. Further
      evaluation of the treatment efficacy would be difficult because of the scarcity
      of such cases.

PMID- 16884425
TI  - Reversible findings of restricted diffusion in 5-fluorouracil neurotoxicity.
AB  - A 35-year-old woman presented with neurotoxicity correlated to an i.v. regimen of
      5-fluorouracil as episodes of acute confusional state and abnormalities of
      symmetrically restricted diffusion in the periventricular white matter and corpus
      callosum. On discontinuing the medication, the areas of severely restricted
      diffusion had entirely resolved, with minimal residual T2 signal abnormality. In
      this case, immediate discontinuation of the chemotherapeutic agent apparently
      reversed the patient's symptoms and findings on MRI. The scant information
      available in the published literature regarding this phenomenon is reviewed with
      regard to 5-fluorouracil.

PMID- 16884426
TI  - Diagnostic error due to vicarious excretion of rectal iodinated contrast.
AB  - Introduction of iodinated contrast into the intact colon is not expected to
      result in imaging-visible renal excretion of this contrast and is a phenomenon
      that has only rarely been described. We present a case in which such vicarious
      renal excretion was misinterpreted as a recto-vesical fistula which resulted in
      unnecessary delay in the patient's management.

PMID- 16884427
TI  - Solid and cystic papillary epithelial neoplasm of the pancreas in an 11-year-old
      girl: imaging features with pathological correlation.
AB  - Solid and cystic papillary epithelial neoplasms (SCPEN) of the pancreas are rare
      tumours seen in young women. Pancreatic masses in children are extremely rare and
      SCPEN should be considered in the radiological differential diagnosis. Although
      there have been many series of SCPEN reported in the published literature in
      adults, only two series have focused on paediatric patients. The radiological and
      histopathological features of SCPEN in a paediatric patient are presented.

PMID- 16884428
TI  - Use of intra-arterial multi-detector row CT angiography for the evaluation of an
      ischaemic limb in a patient with renal impairment.
AB  - The vastly improved scanning speed and z-axis resolution afforded by multi
      detector technology has allowed CT to refine its traditional roles and to explore
      many new applications in imaging. We present a case report of a patient with
      renal failure and an ischaemic leg, which illustrates a useful new CT vascular
      imaging application. By carrying out 16-channel multi-detector row CT angiography
      through a sheath introduced into the common femoral artery, we obtained a high
      quality angiographic image of the affected leg, using only 30 mL of iodinated
      contrast material. The examination definitively showed the number, distribution
      and patency of the tibial run-off arteries, with significant influence on the
      patient's subsequent clinical management. This simple and relatively minimally
      invasive technique is useful in peripheral vascular imaging, when conventional CT
      angiography using a large volume of i.v. contrast and MR angiography are
      unsuitable or unavailable.

PMID- 16884429
TI  - Iliocaval arteriovenous fistula presenting with multiple organ failure.
AB  - Iliac arteriovenous fistulas are an uncommon condition, which may be spontaneous
      or traumatic in nature. Such fistulas classically present with a triad of high
      output cardiac failure, pulsatile abdominal mass with a bruit and unilateral leg
      ischaemia or venous congestion. We describe a case of an iliocaval fistula
      secondary to rupture of a common iliac artery aneurysm, with an unusual
      presentation of multiple organ failure, masquerading as sepsis. We describe the
      CT findings of iliocaval fistula, which was the means of diagnosis in this study.

PMID- 16884430
TI  - Haemophilic pseudotumour presenting with large bowel obstruction.
AB  - Osseous haemophilic pseudotumours are uncommon. The commonest sites of
      involvement are the femur and the pelvis. Trauma is the initiating factor in most
      reported cases and repeated bleeding into the lesion contributes to their growth.
      Most lesions grow slowly and are often asymptomatic. Complications include
      massive haemorrhage, infection and pathological fracture. We present an extremely
      unusual presentation where a large haemophilic pseudotumour of the pelvis
      extended to impinge the adjacent colon, resulting in large bowel obstruction.

PMID- 16884431
TI  - Direct sac puncture and N-butyl cyanoacrylate embolization of medial canthal
      arteriovenous malformation supplied by the external carotid artery and the
      internal carotid artery branches.
AB  - We report a periorbital arteriovenous fistula that was treated with direct sac
      puncture N-butyl cyanoacrylate embolization under controlled inflow and outflow.
      The efficacy of this technique in a periorbital lesion is discussed.

PMID- 16884432
TI  - Iatrogenic secondary post-partum haemorrhage: apropos of two uncommon cases.
AB  - In this article we would like to highlight uterine pseudoaneurysm as a cause of
      secondary post-partum haemorrhage following Caesarean section. We would like to
      stress Doppler ultrasound scan as the initial screening modality for this
      condition. We also describe angioembolization as the prudent treatment option for
      this condition rather than resorting to surgery.

PMID- 16884433
TI  - Leiomyosarcoma of the inferior vena cava.
AB  - Leiomyosarcoma of the inferior vena cava is a rare primary tumour. We present a
      case report of a 67-year-old man with a long history of abdominal pain and
      gastroesophageal reflux, who was found to have a large retroperitoneal mass
      confirmed to be a leiomyosarcoma. The clinical and imaging features are outlined,
      and in addition the treatment and prognosis.

PMID- 16884434
TI  - Spontaneous coeliac artery dissection.
AB  - A patient with spontaneous coeliac artery dissection that presented as upper
      abdominal pain is reported. This was diagnosed on contrast-enhanced multislice
      helical CT. The patient was treated conservatively and follow-up CT showed mild
      aneurysmal change of the splenic artery and a small splenic infarct. Isolated
      dissection of the visceral arteries (and, in particular, the coeliac artery) is
      extremely rare. With such limited evidence, decisions over best management are
      difficult, but depend on initial severity and progression at follow up.

PMID- 16884438
TI  - Psychosocial impact among the public of the severe acute respiratory syndrome
      epidemic in Taiwan.
AB  - During the 2003 outbreak, severe acute respiratory syndrome (SARS) spread to more
      than 30 countries. Not only did it cause severe health problems but it also
      imposed a great psychological impact on the public. SARS emerged in Taiwan during
      April 2003. This study investigates the psychosocial impact and the associated
      factors of depression of the SARS epidemic in Taiwan when the epidemic had just
      been controlled. A total of 1552 respondents were recruited in the study by
      random selection from the telephone book. Demographic data, SARS experience, self
      perceived health state, neighborhood relationships, and depression were surveyed
      by telephone interviewing. Respondents were grouped as 'impacted group' and 'non
      impacted group' according to whether they or their friends and family had been
      quarantined, or suspected of being infected. The psychosocial impact and
      associated factors were compared between the two groups. The 'impacted group' had
      higher depressive levels, poorer neighborhood relationships, poorer self
      perceived health, and a higher economic impact than the 'non-impacted group'. The
      poorer self-perceived health and economic impact factors were associated with
      depression. The neighborhood relationship factor was negatively associated with
      depression for the 'impacted group', but not for the 'non-impacted group'. The
      'impacted group' had experienced greater psychosocial impact possibly due to the
      SARS impact, the economic downturn, poor self-perceived health conditions, and
      decreased social support systems. An appropriate mental health intervention to
      improve the self-perceived health condition, to provide instrumental and
      psychological support for the 'impacted group', and to decrease the
      stigmatization and discrimination from the public could have buffered the
      psychological impact from this epidemic disaster.

PMID- 16884439
TI  - Clinical predictors of response to pharmacotherapy with selective serotonin
      reuptake inhibitors in obsessive-compulsive disorder.
AB  - The objective of this study was to investigate the clinical predictors of
      response to treatment with selective serotonin reuptake inhibitors (SSRI) in a
      sample of patients with obsessive-compulsive disorder (OCD). A total of 55
      patients diagnosed as OCD according to revised 3rd edition of the Diagnostic and
      Statistical Manual of Mental Disorders criteria underwent a 12-week standardized
      SSRI treatment. According to 'treatment response', defined as at least a 35% drop
      in the Yale-Brown Obsessive-Compulsive Scale total score, OCD patients were
      divided into two groups. A total of 32 (58.2%) patients who responded to
      treatment and 23 (41.8%) who did not, were compared in terms of sociodemographic
      and clinical characteristics. The authors' findings demonstrated that the
      severity of obsession-compulsions and disability in work, social and family lives
      at the beginning of treatment were significantly higher in OCD patients who did
      not respond to treatment in comparison to those who did. Linear regression
      analysis, however, revealed that Sheehan Disability Scale-work score at baseline
      was a predictor of response to SSRI treatment. The higher levels of disability at
      the beginning of treatment in patients with OCD are associated with a poorer
      response to SSRI.

PMID- 16884440
TI  - Clinical features and treatment outcome in Japanese patients with social anxiety
      disorder: chart review study.
AB  - The lifetime prevalence of social anxiety disorder (SAD) is high at 3-13%, but
      there have been only limited reports investigating the clinical features of this
      disorder in a large number of Japanese patients. The authors have conducted a
      retrospective, chart review study of 52 patients with SAD and obtained the
      following results. (i) The proportion of SAD in first visit outpatients at the
      Department of Psychiatry, Niigata University Medical and Dental Hospital,
      Niigata, Japan, was 1.04%. The male : female ratio was 1:0.73, so male patients
      appeared to be more common in the sample. (ii) With regard to subtype,
      generalized type (73% of the patients) was more common than non-generalized type
      (27%). (iii) The mean age of onset was 18.6 +/- 7.8 years, and there was a trend
      towards onset of disease at a younger age in the generalized type compared to the
      non-generalized type. (iv) The most common chief complaint was anxiety and
      tension in front of others (40.4%). (v) Pharmacotherapy resulted in improvement
      in 63.5% of the patients. Treatment by fluvoxamine and alprazolam resulted in
      high response rates of more than 70%.

PMID- 16884441
TI  - Psychological burdens are associated with young male transsexuals in Korea.
AB  - The purpose of this study was to compare differences of the psychological burdens
      between young male transsexuals and age-gender matched non-transsexuals with
      standardized psychiatric rating scales in Korea. A total of 43 biologically
      unrelated young male transsexuals and 49 age-gender matched non-transsexuals
      participated in the study. All subjects completed Beck's Depression Inventory
      (BDI), Social Avoidance and Distress Scale (SADS), Self-Esteem Scale (SES) and
      Family Adaptability and Cohesion Evaluation Scale (FACES-III). The transsexuals
      showed significantly higher scores on the BDI (P < 0.0001) and SADS (P = 0.002)
      and lower scores on the SES (P < 0.0001) and Adaptability and Cohesion subscales
      (P = 0.016 and P < 0.0001, respectively) of the FACES-III than those of the non
      transsexuals. The present study found young male transsexuals may be potentially
      vulnerable to develop psychiatric and familial problems in comparison with non
      transsexuals, at least in Korea, although methodological limitations exist.
      Further well-designed researches should be launched to confirm this preliminary
      study.

PMID- 16884442
TI  - Effect of age and education on the Trail Making Test and determination of
      normative data for Japanese elderly people: the Tajiri Project.
AB  - The Trail Making Test (TMT) is a common two-part neuropsychological test, in
      which visuospatial ability (TMT-A) and executive function (TMT-B) are evaluated.
      Normative data for this test have not been reported for Japanese subjects;
      therefore, the purpose of the present paper was to investigate the effect of age
      and education on the TMT in 155 healthy elderly adults with clinical dementia
      rating 0 (healthy). The participants were classified into three groups based on
      age (70-74 years, 75-84 years and >or=85 years), and also into three groups based
      on educational level (6 years, 8 years and >or=10 years). The time to complete
      TMT-A and TMT-B were measured, and the difference in score between TMT-A and TMT
      B (B-A) and the ratio of the score (B/A) were calculated as indices of executive
      function. The time for completion of both parts of the TMT increased markedly in
      the >or=85-years group. For TMT-A, there was a significant difference between the
      6-years and 8-years groups, and between the 6-years and >or=10-years groups, and
      for TMT-B, there was a significant difference between the 6-years and >or=10
      years groups, and between the 8-years and >or=10-years groups. The difference and
      ratio scores increased in the >or=85-years group, but the educational level did
      not significantly influence these scores. Our data suggest that cognitive
      functions evaluated by TMT-A and TMT-B are not affected by aging until the
      subjects are >or=85 years old. For TMT-A, an educational effect becomes apparent
      when the population includes poorly educated subjects, but this part of the test
      is not affected by educational level provided that the subjects have some
      education (>6 years). The time to complete TMT-B is affected by educational
      level, consistent with previous reports. However, when adjusted using the results
      for TMT-A [(B-A) or (B/A)], the educational effect on executive function
      disappeared. Thus, the effect of educational level on executive function was
      unclear in normal elderly subjects.

PMID- 16884443
TI  - A naturalistic comparison of two right unilateral electroconvulsive therapy
      dosing protocols: 2-3X seizure threshold versus fixed high-dose.
AB  - The aim of this study was to compare the outcomes associated with two differing
      right unilateral (RUL) electroconvulsive therapy (ECT) dosing protocols: 2-3X
      seizure threshold (2-3X ST) and fixed high dose (FHD) at 353 mC. A retrospective
      chart review was performed to compare patient outcomes during the implementation
      of two different dosing protocols: 2-3X ST from October 2000 to May 2001 and FHD
      from June 2001 to February 2002. A total of 56 patients received ECT under the 2
      3X ST protocol, and 46 received ECT under the FHD protocol. In total, 13.6% of
      patients receiving ECT according to the 2-3X ST protocol received more than 12
      ECT, whereas none of the FHD group received more than 12 ECT. The mean number of
      ECT per treatment course reduced significantly from 7.6 to 5.7 following the
      switch from the 2-3X ST protocol to the FHD protocol. There were no significant
      differences between the two groups in the incidence of adverse cognitive effects.
      ECT practitioners adhered to the 2-3X ST protocol for only 51.8% of ECT courses,
      with protocol adherence improving to 87% following introduction of the FHD
      protocol. Although this naturalistic retrospective chart survey had significant
      methodological limitations, it found that practitioners are more likely to
      correctly adhere to a fixed dose protocol, therefore, increasing its 'real world'
      effectiveness in comparison to titrated suprathreshold dosing techniques. The FHD
      protocol was associated with shorter courses of ECT than the 2-3X ST protocol,
      with no significant difference between the two protocols in clinically
      discernable adverse cognitive effects.

PMID- 16884444
TI  - Attention-deficit/hyperactivity disorder and dissociative disorder among abused
      children.
AB  - The aim of this study was to investigate the psychiatric problems and
      characteristics among children of child abuse (CA). Specifically, the authors
      investigated whether attention-deficit/hyperactivity disorder (ADHD) symptoms
      were exhibited before or after CA. A total of 39 abused child inpatients who were
      treated at Aichi Children's Health and Medical Center, Aichi, Japan, (mean age,
      10.7 +/- 2.6; mean IQ scores, 84.1 +/- 19.3) were included in the study. The most
      frequent diagnosis was dissociative disorder in 59% of abused subjects. ADHD was
      diagnosed in 18% of abused subjects, and 71% of ADHD children had comorbid
      dissociative disorder. A total of 67% of all CA subjects fulfilled the ADHD
      criteria A according to DSM-IV-TR, however, only 27% of those fulfilled the
      criteria before CA. The subjects of dissociative disorder fulfilled ADHD criteria
      A more frequently than those of non-dissociative disorder (P = 0.013), and this
      result led to an increase in the frequency of the apparent ADHD. The rate of ADHD
      suspected parents in the subjects who fulfilled ADHD criteria A after CA was
      significantly lower than those who fulfilled it before CA (P = 0.005). While it
      is difficult to distinguish ADHD from dissociative disorder, abused children may
      have increased apparent ADHD due to dissociative disorder. Further studies should
      be conducted in order to explore the distinct biological differences between ADHD
      before CA and the subjects who fulfilled ADHD criteria A after CA.

PMID- 16884445
TI  - The impact of antistigma education on the attitudes of general practitioners
      regarding schizophrenia.
AB  - The aim of this study was to examine the views and attitudes of general
      practitioners (GP) with respect to schizophrenia, and the changes in their
      attitudes after antistigma education. A total of 106 GPs working in 71 health
      institutions were included in the study. A questionnaire of 16 items, focussing
      on doctors' views and attitudes towards schizophrenia, was applied. Questions
      were about the views and attitudes of doctors towards general myths related to
      schizophrenia. Doctors were asked to select one of two responses: 'I agree' or 'I
      disagree', for statements such as 'schizophrenic patients cannot work' and
      'schizophrenic patients are aggressive and dangerous'. After completing the
      questionnaire, all the GPs were given a single session of antistigma education.
      The questionnaire was repeated 3 months after training meetings in a subsample of
      54 GPs which represented the whole sample in terms of gender, age, and years in
      medical practice. The authors found statistically significant, positive changes
      on five items out of the 16 items in the post-test survey when compared to
      attitudes before training, including items about the treatability of
      schizophrenia, harmfulness and untrustworthiness of schizophrenic patients. The
      authors' findings suggest that one antistigma education session, supported by the
      distribution of related documents, can improve GPs attitudes towards
      schizophrenia.

PMID- 16884446
TI  - Recidivism among male subjects incarcerated for illicit drug use in Taiwan.
AB  - Illicit drug users are generally considered both patients and criminals in
      Taiwan. This study presents drug use behaviors and criminal recidivism of male
      subjects incarcerated for illicit drug use in Taiwan after detoxification at a
      detention center. This study also examined the relationship between drug use
      behaviors and subsequent recidivism. Charts and crime records of 794 male
      patients from the acute detoxification unit in a detention center in northern
      Taiwan were reviewed. These subjects were incarcerated for methamphetamine or/and
      heroin use. The authors examined the relationship between the variables collected
      during detoxification and subsequent recidivism of illicit drug use in the
      following 5 years after detoxification. Of 794 subjects, 539 (67.9%) were repeat
      offenders during the following 5 years after detoxification. Their recidivism
      occurred primarily within the first 2 years after being released into the
      community. The recidivism rate for heroin users was significantly higher than
      that of methamphetamine users. Aged under 30 years, a previous criminal record,
      and a positive urine analyses test for illicit drugs upon entering the
      detoxification unit were significantly associated with recidivism. Recidivism
      rates of illicit drug users in Taiwan after detoxification in the detention
      center were substantially high. The efficacy of detoxification programs at
      detention centers in Taiwan needs to be re-evaluated.

PMID- 16884447
TI  - Long-term clinical course of patients with acute polymorphic psychotic disorder
      without symptoms of schizophrenia.
AB  - Few studies have investigated the long-term course of patients with acute
      polymorphic psychotic disorder, despite the clinical relevance. The present study
      focused on the frequency of acute polymorphic psychotic disorder without symptoms
      of schizophrenia (F23.0) and the prognosis of patients with the disorder over a
      long period. A total of 388 inpatients with nonaffective psychosis were examined
      and cases with F23.0 were retrospectively investigated regarding clinical course
      over 12 years with reference to clinical charts. A total of 16 cases were
      diagnosed with F23.0 according to first episode. After 12 years, five cases were
      rediagnosed with schizophrenia, and one case with borderline-type emotionally
      unstable personality disorder, although the diagnosis of F23.0 was not changed in
      10 older patients. Of the four cases with >2 repeated episodes of F23.0, the same
      clinical picture as in the first episode was observed in three, while one case
      showed continuous residual symptoms. F23.0 does not represent a homogeneous
      clinical entity. In some cases, diagnosis changes to schizophrenia, but others
      display repeated episodes of F23.0.

PMID- 16884448
TI  - Total antioxidant response in patients with schizophrenia.
AB  - There is a large amount of convincing data demonstrating that reactive oxygen
      species (ROS) are involved in initiation and development of many different forms
      of neuropsychiatric disorders. The levels of oxidants and antioxidants in
      schizophrenia have been evaluated. However, measurements of total antioxidant
      response (TAR) were not evaluated up to now. Therefore, the objectives of this
      study are to investigate plasma TAR levels in schizophrenia subtypes. A total of
      76 patients with schizophrenia and 25 healthy volunteers were included in the
      study. Positive and Negative Syndrome Scale (SANS and SAPS, respectively) were
      applied to patients. TAR values were determined in the plasma of normal healthy
      controls and patients with schizophrenia. Plasma TAR levels of each schizophrenia
      subtype were significantly lower than healthy controls (P < 0.01 for
      disorganized, residual and undifferentiated subtypes and P < 0.01 for paranoid
      subtype). When intragroup comparisons were performed, paranoid subtype had higher
      plasma TAR levels compared to other subtypes (P < 0.01). Accordingly, as a whole
      group, patients with schizophrenia had lower plasma TAR levels compared to
      controls. Plasma TAR levels were significantly and negatively correlated with
      SANS scores, and duration of illness was evaluated but not related to other
      parameters. Consequently, the present study further emphasizes the growing
      consideration that free radical damage may have an important etiopathogenetic
      role on the development of schizophrenia and suggests that decreased plasma total
      antioxidant levels may be related to the progression of illness.

PMID- 16884449
TI  - Executive dysfunctions and depression in Behcet's disease without explicit
      neurological involvement.
AB  - This study aims to assess the executive functions and depression status in
      patients with Behcet's disease without explicit neurological involvement and to
      evaluate cognitive functions in this group of patients independent of
      accompanying depression. In the present study, 30 patients with Behcet's disease
      in the non-active phase of their illness and 30 healthy volunteers were included.
      In the evaluation of depression levels, Beck Depression Inventory was employed.
      The executive functions of the patients were evaluated by Wisconsin Card Sorting
      Test (WCST) and Stroop Test (ST). Beck Depression Inventory scores measured in
      the Behcet's disease group, in which no clinically serious depression was
      observed, were higher than the control group. Then, it was observed that the
      scores of neuropsychological tests of the Behcet's disease group were found to be
      significantly lower, especially in WCST, while significant relations were
      revealed between Beck Depression Inventory scores and WCST, ST scores. The
      authors' findings suggest that there may be factors other than depression causing
      executive impairment in patients with Behcet's disease without explicit
      neurological symptoms. Executive dysfunctions may occur in association with mild
      depressive states due to chronic disease stress or silent and/or future
      neurological involvement of Behcet's disease, especially in the frontal lobes.

PMID- 16884450
TI  - Cognitive function and social abilities in patients with schizophrenia:
      relationship with atypical antipsychotics.
AB  - Although atypical antipsychotics have been associated with improvements in
      cognitive function in schizophrenia, the neurochemical basis for such effects is
      not well understood. Candidate neurotransmitter systems primarily involve
      dopamine and serotonin. The current study explored this issue by examining the
      cognitive abilities, social function and quality of life in patients with
      schizophrenia who were medicated with atypical antipsychotics. Comparisons were
      done for matched schizophrenia patients who were on antipsychotics with (i) an
      affinity for multiple receptors (olanzapine, clozapine, quetiapine) versus those
      that have preferential affinity for dopamine receptors (risperidone,
      amisulpride); and patients on medication with (ii) a high affinity for serotonin
      (5HT-2A) receptors (risperidone, olanzapine, clozapine) versus those with a low
      (or no) affinity for 5HT-2A receptors (quetiapine, amisulpride). No differences
      emerged between groups on any cognitive or social variable when the groups were
      compared for the dopaminergic properties of antipsychotic medication. By
      contrast, differences did emerge when patients were compared on the 5HT-2A
      affinity of their antipsychotic medications. Patients on low 5HT-2A-affinity
      antipsychotics exhibited a better performance on a measure of selective attention
      and adjustment to living. These findings accord with the notion that serotonergic
      mechanisms are important determinants of both the cognitive and the social
      effects of the atypical antipsychotics.

PMID- 16884451
TI  - Adult attention-deficit hyperactivity disorder in patients with bipolar I
      disorder in remission: preliminary study.
AB  - Attention-deficit hyperactivity disorder (ADHD), a syndrome that typically first
      appears in early childhood, can occur in individuals of all ages. Prospective
      studies have demonstrated that at least half of children diagnosed as having ADHD
      continue to suffer the symptoms of this disorder in their adult life with
      significant impacts on their social status, achievement level and sense of well
      being. The purpose of this preliminary study was to determine the rate of ADHD in
      patients with bipolar disorder (BD) and to examine the effects of comorbid ADHD
      on several clinical and sociodemographic variables of bipolar patients. Forty
      four BD-I patients followed up in psychiatric outpatient clinics in two
      university hospitals, were assessed for the presence of adult ADHD according to
      DSM-IV. All patients also completed the Wender Utah Rating Scale for objective
      evaluation of ADHD. Of 44 patients with BD-I, only seven (15.9%) fulfilled
      criteria for a diagnosis of adult ADHD. Bipolar disorder-I patients with comorbid
      ADHD were more likely to be female, and have more affective episodes (especially
      depressive episodes) than bipolar patients without comorbid ADHD. Age at onset of
      affective illness was not significantly different between the two groups. In line
      with results of several previous reports, the present study also showed higher
      prevalence of ADHD in patients with BD-I than in normal population. A higher
      number of affective episode in patients with comorbid ADHD may suggest a more
      severe clinical course of BD in these patients. A larger group of samples is
      required to clarify the exact association and interaction between these two
      clinical entities.

PMID- 16884452
TI  - Adjusting the frequency of continuation and maintenance electroconvulsive therapy
      to prevent relapse of catatonic schizophrenia in middle-aged and elderly patients
      who are relapse-prone.
AB  - The purpose of the present paper was to study the effect of continuation
      electroconvulsive therapy (ECT) on the prevention of relapse in middle-aged and
      elderly patients with intractable catatonic schizophrenia. It was found that
      continuation ECT is efficacious to sustain remission for patients who suffer
      relapse after response to acute ECT despite continuation neuroleptics. However,
      three patients suffered relapse during continuation ECT, therefore the effect of
      adjusting the frequency of continuation ECT and maintenance ECT was investigated
      in these patients with catatonic schizophrenia who relapsed during continuation
      ECT. These patients with DSM-IV catatonic schizophrenia who relapsed during
      continuation ECT were treated with more frequent continuation ECT and subsequent
      maintenance ECT after response to acute ECT. The patients' Brief Psychiatric
      Rating Scale (BPRS) scores were prospectively evaluated until relapse. Patients
      were considered to be relapsers if they had a BPRS score >or=37 for 3 consecutive
      days. The three patients with catatonic schizophrenia who relapsed during
      continuation ECT were treated successfully with more frequent continuation ECT
      and subsequent maintenance ECT. No patient experienced a severe adverse effect
      from continuation or maintenance ECT. More frequent continuation ECT and
      maintenance ECT deserves consideration in middle-aged and elderly patients with
      intractable catatonic schizophrenia who suffer relapse during continuation ECT.
      Large-scale systematic studies are warranted to investigate the optimum use of
      continuation and maintenance ECT in patients with catatonic schizophrenia.

PMID- 16884453
TI  - Reliability and validity of the Bangla version of WHOQOL-BREF in an adult
      population in Dhaka, Bangladesh.
AB  - The aim of the present study was to evaluate the validity and reliability of the
      Bangla version of the World Health Organization Quality of Life questionnaire
      (WHOQOL-BREF) in an adult population in Bangladesh. Approximately 200 adults in
      the Dhaka district were interviewed using a questionnaire containing the Bangla
      version of the WHOQOL-BREF, as well as questions related to sociodemographic
      data. To assess the reliability of WHOQOL-BREF, Cronbach's alpha was calculated,
      and test-retest reliability was evaluated using intraclass correlation
      coefficient (ICC) of the first and second administrations. For comparison,
      approximately 200 leprosy patients were also interviewed with the questionnaire
      to examine the discriminant validity between groups. On the whole, sufficient
      validity was observed, and the Bangla version of the WHOQOL-BREF was deemed to be
      valid and reliable in assessing the quality of life of an adult population in
      Bangladesh.

PMID- 16884454
TI  - Chronic intraperitoneal injection of interferon-alpha reduces serotonin levels in
      various regions of rat brain, but does not change levels of serotonin transporter
      mRNA, nitrite or nitrate.
AB  - Interferon-alpha therapy is associated with a high rate of depression, but the
      pathophysiological mechanisms remain unclear. The purpose of the present study
      was to investigate the effects of i.p. administered interferon-alpha on
      monoaminergic neurotransmission in the brain. The levels of monoamines and
      associated metabolites were measured in various regions of the rat brain using a
      high-performance liquid chromatography-electrochemical detection system. The
      serotonin transporter mRNA levels were also measured using in situ hybridization.
      After 1 day, dopamine turnover was diminished in the cortex. Norepinephrine
      turnover was decreased in most regions tested after 4 days. However, these
      changes were transient. After 14 days, serotonin turnover was increased in the
      frontal cortex and hippocampus in rats given a dose of 20 000 IU/kg; in the
      frontal cortex, hippocampus, amygdala, thalamus, hypothalamus and brainstem in
      those on 200 000 IU/kg; and in the thalamus and hypothalamus in those on 2 000
      000 IU/kg (all P < 0.05). However, 14-day treatment did not significantly change
      serotonin transporter mRNA levels. Next, the question of whether interferon-alpha
      affects monoamine levels via induction of nitric oxide (NO), was investigated.
      However, there were no changes in either NO2- or NO3-, as markers of NO
      production, in any brain regions after 14-day treatment. These results suggest
      that chronic peripheral administration of interferon-alpha induces metabolic
      changes in the central serotonin system. Further investigation is needed to
      determine exactly how this cytokine affects the central serotonin system and to
      assess whether a central serotonin abnormality is involved in interferon-induced
      depression.

PMID- 16884455
TI  - Treatment of partial seizures with gabapentin: double-blind, placebo-controlled,
      parallel-group study.
AB  - This double-blind study was conducted to evaluate the efficacy and safety of
      gabapentin 1200 mg/day and 1800 mg/day (t.i.d.) compared to placebo as an
      adjunctive therapy in patients with refractory epilepsy. Patients were included
      when they had partial seizures at least eight times during a 12-week baseline
      period despite treatment with one to two antiepileptic drugs. After baseline,
      eligible patients were randomized to gabapentin 1200 mg/day, 1800 mg/day, or
      placebo for 12-week treatment. The primary end-point, response ratio, was derived
      from seizure frequencies during treatment and baseline period based upon the
      seizure daily record by a patient. Of the 209 randomized patients, 86 received
      gabapentin 1200 mg/day, 41 received gabapentin 1800 mg/day, and 82 received
      placebo. A statistically significant difference was found between each of the two
      gabapentin groups and placebo for the primary efficacy end-point, response ratio
      (P < 0.005) with definite dose-response (P < 0.001). More gabapentin patients
      reported moderate to marked improvement in seizure frequency and
      intensity/duration of each seizure than placebo patients. Treatment-related
      adverse events were reported by approximately 65% of patients receiving
      gabapentin compared to approximately 46% of patients receiving placebo;
      somnolence and dizziness were the most common events. Gabapentin 1200 mg/day and
      1800 mg/day significantly reduced the frequency of refractory seizures compared
      to placebo. Favorable tolerability of gabapentin was confirmed also in a Japanese
      population, consistent with previous global studies.

PMID- 16884456
TI  - Transient global amnesia following a transoceanic flight.
AB  - Transient global amnesia (TGA) is the abrupt onset of temporary anterograde
      amnesia without any focal neurological features. It is a benign condition and is
      completely reversible in most cases. However, the sudden occurrence of memory
      impairment can be especially alarming to an individual who has recently arrived
      in an unfamiliar setting. The cause of TGA remains unknown. Reported here is the
      unusual occurrence of TGA in a man following the completion of an international
      airplane flight. Possible etiologies of the episode are considered.

PMID- 16884457
TI  - Routine use of operational diagnostic criteria affects the pharmacotherapy of
      dysthymia: national questionnaire survey of experienced psychiatrists in Japan.
AB  - The purpose of the present paper was to evaluate, with the use of a
      questionnaire, how Japanese psychiatrists diagnose and treat a typical adult
      dysthymia case. Clinicians who routinely use operational diagnostic criteria
      (ODC) had more correct diagnoses than those who did not. Approximately 70% of
      psychiatrists who routinely use ODC chose selective serotonin re-uptake
      inhibitors (SSRI) as the first choice of treatment, while of those psychiatrists
      who do not use these criteria, only half prescribed SSRI. This difference was
      statistically significant (P = 0.01). The results of the present study suggest
      that psychiatrists who are familiar with ODC tend to treat dysthymia according to
      evidence-based pharmacotherapy.

PMID- 16884458
TI  - Association between corticotropin-releasing hormone receptor 2 (CRHR2) gene
      polymorphism and personality traits.
AB  - Corticotropin-releasing hormone (CRH) has been implicated in the pathophysiology
      of anxiety disorders and depression. Corticotropin-releasing hormone receptor 2
      (CRHR2) is one of the receptors that mediate CRH signal. The purpose of the
      present study was to investigate the association between the CRHR2 gene and
      personality traits, evaluated using the Revised NEO Personality Inventory (NEO PI
      R), in 243 healthy Japanese subjects. As a result, significant association was
      observed between the polymorphism in intron 2 (rs2267717) and Openness (P =
      0.004, uncorrected, anova), while no relationship was observed concerning
      Neuroticism. The present result suggests an association between CRHR2 and the
      personality trait of Openness.

PMID- 16884459
TI  - Is Asperger syndrome associated with abnormal nocturnal motor phenomena?

PMID- 16884460
TI  - Counterbalance between leptin and cortisol may be associated with fibromyalgia.

PMID- 16884462
TI  - Surfactant treatment in the ICU: alternative interpretations of existing
      evidence.

PMID- 16884463
TI  - The management of pulmonary hypertension.

PMID- 16884464
TI  - Psychological effects of repeated general anesthesia in children.
AB  - BACKGROUND: Although methods for reducing preoperative anxiety have been a major
      interest of pediatric anesthesiologists, there are no reports of the effects of
      repeated anesthesia on psychological development of children. METHODS: To
      determine the overall effect of multiple anesthetics on the psychology of
      children, we undertook to compare the children undergoing repeated anesthesia
      (Group S) for the treatment of corrosive esophagitis with a control group (Group
      C) with chronic renal disease and frequent hospital admissions. Psychological
      tests and diagnosis of children Group S (n = 23) were compared prospectively with
      Group C (n = 20). All children had been appropriately treated over the previous 5
      years and 50% of patients in Group C had general anesthesia once and those in
      Group S underwent at least 5 GAs. Parents completed a child behavior checklist
      (CBCL) and Marital Conflict Questionnaire; the children were evaluated by a child
      psychiatrist using DSM-IV criteria and completed the Child Depression Inventory
      (CDI). RESULTS: The children in Group S underwent a total of 251 (11 +/- 7) GAs
      over 4-60 months. The incidence of psychopathology was nine and 10 children in
      groups S and C, respectively. The CBCL and CDI scores were parallel with a
      psychiatric diagnosis. Marital conflict scores were higher in Group S.
      CONCLUSIONS: Both chronic disease states affect psychology of children. Repeated
      anesthesia in addition to chronic disease does not seem to disturb the child's
      psychological health further when tentative and precautious approach modalities
      are undertaken.

PMID- 16884465
TI  - The effects of caudal local anesthesia blockade on the Bispectral Index during
      general anesthesia in children.
AB  - BACKGROUND: Peripheral deafferentation induced by epidural or spinal anesthesia
      reduces the degree of cortical arousal in adults. This study aimed at determining
      if caudal blockade decreases the level of arousal, as measured by Bispectral
      Index (BIS) in unstimulated children, and to determine if this effect differed
      between age groups. METHODS: Hospital ethics committee approval and parental
      consent was obtained. Children (age between 24 months and 5 years) and infants
      (between 6 and 24 months of age) were recruited if they were scheduled for below
      umbilical surgery that would usually require caudal local anesthesia blockade.
      Before the procedure, subjects within each age group were randomized to either
      caudal group (1 ml.kg(-1) 0.25% bupivacaine), or control group (no caudal). In
      all groups, anesthesia was induced with sevoflurane and maintained at a constant
      endtidal concentration of 1.5% sevoflurane without N(2)O. Five minutes after
      induction a baseline BIS was recorded (BIS(1)). In the caudal groups, a caudal
      block was then performed while in the control groups no block was performed.
      Fifteen minutes later, the BIS was again recorded (BIS(2)). The change in BIS
      over this time period was the primary outcome (BIS(Delta)). After measurement,
      subjects in the control groups received a caudal block before the start of
      surgery. RESULTS: Twenty-nine infants and 18 children completed the study
      protocol. In children, BIS(Delta) was significantly different between the caudal
      group and control (-5.7 vs -0.7, P = 0.04). In infants, no significant difference
      was detected in BIS(Delta) between caudal and control groups. CONCLUSIONS: Caudal
      blockade decreased the degree of arousal, as measured by BIS, in unstimulated
      children aged 2-5 years. No change in arousal was detected in infants.

PMID- 16884466
TI  - Oral clonidine premedication reduces minimum alveolar concentration of
      sevoflurane for laryngeal mask airway insertion in children.
AB  - BACKGROUND: Sevoflurane is widely employed for inhalational induction in
      children. Clonidine deepens volatile anesthetics and reduces several types of MAC
      of sevoflurane. Laryngeal mask airway is a useful device for pediatric
      anesthesia. The aim of the current study was to determine whether oral clonidine
      premedication can reduce MAC of sevoflurane for an LMA insertion in children.
      METHODS: Fifty-six ASA physical status I patients (3-11 years) scheduled for
      general anesthesia were randomly divided into two groups of 28 patients each. One
      group (clonidine group) received clonidine 4 microg x kg(-1) approximately 100
      min before anesthesia, and the other (control) group did not. Anesthesia was
      induced with sevoflurane. Each concentration of sevoflurane, at which an LMA
      insertion was attempted, was predetermined according to the modification of
      Dixon's up-and-down method with 0.25% as a step size and held constant for at
      least 20 min before the trial. All responses ('movement' or 'no movement') to an
      LMA insertion were assessed. RESULTS: Minimum alveolar concentration values of
      sevoflurane for an LMA insertion were lower in the clonidine group (1.31% +/-
      0.18% [mean +/- sd]) than in the control group (2.00% +/- 0.16%). Logistic
      regression analysis revealed that sevoflurane EC95 values were 1.79% and 2.49% in
      the clonidine and control groups, respectively. CONCLUSIONS: Oral clonidine
      premedication reduced the MAC (EC50) and EC95 values of sevoflurane for LMA
      insertion by 38% and 28%, respectively.

PMID- 16884467
TI  - Rocuronium 0.3 mg x kg-1 (ED95) induces a normal peak effect but an altered time
      course of neuromuscular block in patients with Duchenne's muscular dystrophy.
AB  - BACKGROUND: In patients with Duchenne's muscular dystrophy (DMD) recovery from
      neuromuscular block is delayed. It has been assumed that this is because of a
      higher potency of muscle relaxants in this patient cohort. We determined the peak
      effect, and the time course of action of rocuronium 0.3 mg x kg(-1) (ED(95)) in
      DMD patients. METHODS: Twenty-four patients (12 with DMD and 12 controls; aged 10
      18 years) were studied. All patients were anesthetized with propofol and
      fentanyl/remifentanil. Neuromuscular transmission was monitored by
      acceleromyography. After induction all patients received a single dose of
      rocuronium 0.3 mg x kg(-1). The complete time course of action as onset, peak
      effect and spontaneous recovery was recorded. RESULTS: The onset time (s) to
      maximum block was significantly (P < 0.01) prolonged in DMD patients (median:
      315; range: 120-465) compared with controls (195, 75-270). The peak effect (%
      twitch depression relative to baseline) was not different between the groups
      (DMD: 59-100; controls: 28-100). In the DMD group, recovery was significantly (P
      < 0.01) delayed compared with controls at all recorded time points. The clinical
      duration (min) was 40.3 (22-89) in the DMD group vs 9.8 (6-17) in the control
      group (P < 0.01). CONCLUSIONS: The similar peak effect in both groups does not
      confirm the thesis of rocuronium having a higher potency in DMD patients. The
      documented very long recovery after the ED(95) of rocuronium emphasizes the need
      for careful assessment of neuromuscular function in DMD patients.

PMID- 16884468
TI  - A cohort study of the incidence and risk factors for negative behavior changes in
      children after general anesthesia.
AB  - BACKGROUND: Hospitalization and anesthesia can have a substantial psychological
      impact on children, which may be manifested by negative behavioral change. The
      primary aims of this study were to estimate the incidence of negative behavior
      change postanesthesia in a large cohort of children, and to identify the possible
      risk factors. METHODS: One thousand two hundred and fifty children aged from 3 to
      12 years scheduled for anesthesia for a variety of procedures were enrolled. The
      absolute version of the Vernon Post Hospitalization Behavior Questionnaire (PHBQ)
      was used to assess behavior change at 3 and 30 days postanesthesia. Deterioration
      in seven or more items of behavior was defined to be a significant negative
      behavior change. Demographic data, anesthesia details, type and extent of
      preparation, details of procedure and length of hospitalization were recorded.
      Child temperament, child anxiety and parental anxiety were also measured.
      RESULTS: Twenty-four percent of children had significant negative behavior change
      at day 3 and 16% at day 30. After logistic regression, factors associated with
      significant negative behavior change at 3 days were increased parental state
      anxiety, younger age, overnight admission, lower birth order and preparation via
      having a discussion with the anesthetist. At day 30, longer hospitalization,
      younger age, reading the anesthesia preparation book and a previous difficult
      anesthesia experience were associated with significant negative behavior change.
      Also at day 30, reading the anesthesia preparation book was strongly associated
      with negative behavior change in children having short procedures, but not longer
      procedures. However, at both 3 and 30 days, the amount of variability explained
      by factors included in the models was low. CONCLUSIONS: Significant negative
      behavior change can occur in children after anesthesia. It is difficult to
      precisely predict in which children this will occur, however, some individual,
      family and procedural variables are associated with significant negative behavior
      change. If used, preparation should be considered according to level of surgical
      complexity.

PMID- 16884469
TI  - Perioperative cardiac arrest and its mortality in children. A 9-year survey in a
      Brazilian tertiary teaching hospital.
AB  - BACKGROUND: The incidence of perioperative cardiac arrest and mortality in
      children is higher than in adults. This survey evaluated the incidence, causes,
      and outcome of perioperative cardiac arrests in a pediatric surgical population
      in a tertiary teaching hospital between 1996 and 2004. METHODS: The incidence of
      cardiac arrest during anesthesia was identified from an anesthesia database.
      During the study period, 15,253 anesthetics were performed in children. Data
      collected included patient demographics, surgical procedures (elective, urgent,
      or emergency), ASA physical status classification, anesthesia provider
      information, type of surgery, surgical areas, and outcome. All cardiac arrests
      were reviewed and grouped by the cause of arrest and death into one of four
      groups: totally anesthesia-related, partially anesthesia-related, totally surgery
      related, or totally child disease or condition-related. RESULTS: There were 35
      cardiac arrests (22.9 : 10,000) and 15 deaths (9.8 : 10,000). Major risk factors
      for cardiac arrest were neonates and children under 1 year of age (P < 0.05) with
      ASA III or poorer physical status (P < 0.05), in emergency surgery (P < 0.05),
      and general anesthesia (P < 0.05). Child disease/condition was the major cause of
      cardiac arrest or death (P < 0.05). There were seven cardiac arrests because of
      anesthesia (4.58 : 10,000)--four totally (2.62 : 10,000) and three partially
      related to anesthesia (1.96 : 10,000). There were no anesthesia attributable
      deaths reported. The main causes of anesthesia attributable cardiac arrest were
      respiratory events (71.5%) and medication-related events (28.5%). CONCLUSIONS:
      Perioperative cardiac arrests were relatively higher in neonates and infants than
      in older children with severe underlying disease and during emergency surgery.
      The fact that all anesthesia attributable cardiac arrests were related to airway
      management and medication administration is important in prevention strategies.

PMID- 16884470
TI  - Use of the Esophageal Doppler Machine to help guide the intraoperative management
      of two children with pheochromocytoma.
AB  - The anesthetic management of pheochromocytoma has been based upon the
      intraoperative control of blood pressure and fluid balance following adequate
      preoperative preparation. This can be difficult, especially in the presence of
      significant comorbidity such as cardiac or renal dysfunction. Two cases of
      children with pheochromocytoma are reported where the introperative management of
      fluid balance and blood pressure control were guided by measurement of changes in
      descending aortic blood flow using an esophageal Doppler probe. The advantages of
      such a technique compared with more invasive monitors are discussed.

PMID- 16884471
TI  - Raised intracranial pressure in a neonate presenting as stridor.
AB  - Neonatal stridor is an important sign of upper airway obstruction. This is most
      commonly secondary to laryngeal pathology and investigated by otolaryngologists.
      However neurological causes of stridor, secondary to vocal cord paralysis also
      occur for a variety of reasons (1). In cases of meningomyelocele up to 20% of
      infants may develop stridor (2). Respiratory distress may be severe and require
      prompt surgical and medical intervention. We describe a neonate born with a
      meningomyelocele, who developed stridor secondary to evolving hydrocephalus after
      surgical repair of the meningomyelocele. This was treated acutely by direct
      tapping of cerebrospinal fluid from the right coronal horn via the coronal suture
      with immediate symptomatic improvement prior to a definitive shunt procedure.

PMID- 16884472
TI  - Anesthesia for sickle cell disease and congenital myopathy in combination.
AB  - We report on the perioperative management of anesthesia and analgesia in a child
      with sickle cell disease and a congenital myopathy, presenting for corrective
      orthopedic surgery. The case illustrates two valuable points of interest: the
      many benefits of regional anesthesia in complex medical cases and the successful
      use of tourniquets in children with sickle cell disease.

PMID- 16884473
TI  - Continuous infraclavicular brachial plexus block in a child.
AB  - Continuous regional anesthesia for both intra- and postoperative use in adults is
      becoming more common. As with many new anesthesia techniques, however, there is
      often a lag time before the same techniques are utilized in children. Our patient
      was a 10-year-old child requiring reoperation on her fifth digit with planned 48
      h admission for range of motion exercises. We wanted to have a continuous
      regional blockade to control the patient's pain during the postoperative
      manipulations of the digit. A search of the literature from the last 10 years did
      not show any reports of the placements of a continuous brachial plexus block in
      children. In this case report, we present the successful placement and use of a
      continuous infraclavicular catheter in a child undergoing upper extremity
      surgery.

PMID- 16884474
TI  - Extravasation of propofol is associated with tissue necrosis in small children.
AB  - Propofol is widely used for induction of anesthesia and many reports document
      extravasation and even intra-arterial injections without clinical sequelae. We
      report a case of tissue necrosis after subcutaneous injection of propofol in a 31
      day-old infant.

PMID- 16884475
TI  - Intraoperative hyperthermia in a child with neuroblastoma.
AB  - The development of intraoperative hyperthermia has been reported in association
      with blood malignancies. This is case report of hyperthermia in a child with
      neuroblastoma, which was not an episode of malignant hyperthermia as determined
      by arterial blood cases and physiologic vital signs.

PMID- 16884476
TI  - Unexpected prolonged paralysis after mivacurium in a patient with Bamforth
      syndrome.

PMID- 16884477
TI  - Airway rescue with laryngeal mask airway during sclerotherapy of a large
      arteriovenous malformation in the oral and maxillofacial region.

PMID- 16884479
TI  - A technique to improve the safety of laryngeal mask airway when used in lacrimal
      duct surgery.

PMID- 16884480
TI  - Failure to thrive in children with cleft lips and palates.

PMID- 16884482
TI  - Ultrasound and caudal blocks in children.

PMID- 16884483
TI  - An unusual position of central venous catheter. Please, not so deep!

PMID- 16884486
TI  - The structural basis of calpain behavior.

PMID- 16884487
TI  - Calpain involvement in the remodeling of cytoskeletal anchorage complexes.
AB  - Cells offer different types of cytoskeletal anchorages: transitory structures
      such as focal contacts and perennial ones such as the sarcomeric cytoskeleton of
      muscle cells. The turnover of these structures is controlled with different
      timing by a family of cysteine proteases activated by calcium, the calpains. The
      large number of potential substrates present in each of these structures imposes
      fine tuning of the activity of the proteases to avoid excessive action. This
      phenomenon is thus guaranteed by various types of regulation, ranging from a
      relatively high calcium concentration necessary for activation, phosphorylation
      of substrates or the proteases themselves with either a favorable or inhibitory
      effect, possible intervention of phospholipids, and the presence of a specific
      inhibitor and its possible degradation before activation. Finally, formation of
      multiprotein complexes containing calpains offers a new method of regulation.

PMID- 16884488
TI  - Calpain 3: a key regulator of the sarcomere?
AB  - Calpain 3 is a 94-kDa calcium-dependent cysteine protease mainly expressed in
      skeletal muscle. In this tissue, it localizes at several regions of the sarcomere
      through binding to the giant protein, titin. Loss-of-function mutations in the
      calpain 3 gene have been associated with limb-girdle muscular dystrophy type 2A
      (LGMD2A), a common form of muscular dystrophy found world wide. Recently,
      significant progress has been made in understanding the mode of regulation and
      the possible function of calpain 3 in muscle. It is now well accepted that it has
      an unusual zymogenic activation and that cytoskeletal proteins are one class of
      its substrates. Through the absence of cleavage of these substrates, calpain 3
      deficiency leads to abnormal sarcomeres, impairment of muscle contractile
      capacity, and death of the muscle fibers. These data indicate a role for calpain
      3 as a chef d'orchestre in sarcomere remodeling and suggest a new category of
      LGMD2 pathological mechanisms.

PMID- 16884489
TI  - Implication of calpain in neuronal apoptosis. A possible regulation of
      Alzheimer's disease.
AB  - Apoptotic neuronal cell death is the cardinal feature of aging and
      neurodegenerative diseases, but its mechanisms remain obscure. Caspases, members
      of the cysteine protease family, are known to be critical effectors in central
      nervous system cellular apoptosis. More recently, the calcium-dependent
      proteases, calpains, have been implicated in cellular apoptotic processes.
      Indeed, several members of the Bcl-2 family of cell death regulators, nuclear
      transcription factors (p53) and caspases themselves are processed by calpains.
      Progressive regional loss of neurons underlies the irreversible pathogenesis of
      various neurodegenerative diseases such as Alzheimer's disease in adult brain.
      Alzheimer's disease is characterized by extracellular plaques of amyloid-beta
      peptide aggregates and intracellular neurofibrillary tangles composed of
      hyperphosphorylated tau leading to apoptotic cell death. In this review, we
      summarize the arguments showing that calpains modulate processes that govern the
      function and metabolism of these two key proteins in the pathogenesis of
      Alzheimer's disease. To conclude, this article reviews our understanding of
      calpain-dependent apoptotic neuronal cell death and the ability of these
      proteases to regulate intracellular signaling pathways leading to chronic
      neurodegenerative disorders such as Alzheimer's disease. Further research on
      these calpain-dependent mechanisms which promote or prevent cell apoptosis should
      help us to develop new approaches for preventing and treating neurodegenerative
      disorders.

PMID- 16884490
TI  - Functional interaction of Escherichia coli heat-labile enterotoxin with blood
      group A-active glycoconjugates from differentiated HT29 cells.
AB  - Human colon adenocarcinoma cells (HT29-ATCC) and the clone HT29-5F7 were cultured
      under conditions that differentiate cells to a polarized intestinal phenotype.
      Differentiated cells showed the presence of junctional complexes and
      intercellular lumina bordered by microvilli. Intestinal brush border hydrolase
      activities (sucrase, aminopeptidase N, lactase and maltase) were detected mainly
      in differentiated HT29-ATCC cells compared with the differentiated clone, HT29
      5F7. The presence of non-GM1 receptors of Escherichia coli heat-labile
      enterotoxin (LT-I) on both types of differentiated HT29 cells was indicated by
      the inability of cholera toxin B subunit to block LT-I binding to the cells.
      Binding of LT-I to cells, when GM1 was blocked by the cholera toxin B subunit,
      was characterized by an increased number of LT-I receptors with respect to
      undifferentiated control cells. Moreover, both types of differentiated cells
      accumulated higher amounts of cyclic AMP in response to LT-I than
      undifferentiated cells. Helix pomatia lectin inhibited the binding of LT-I to
      cells and the subsequent production of cyclic AMP. LT-I recognized blood group A
      active glycosphingolipids as functional receptors in both HT29 cell lines and the
      active pro-sucrase form of the glycoprotein carrying A-blood group activity
      present in HT29-ATCC cells. These results strongly suggest that LT-I can elicit
      an enhanced functional response using blood group A-active glycoconjugates as
      additional receptors on polarized intestinal epithelial cells.

PMID- 16884492
TI  - Adipophilin increases triglyceride storage in human macrophages by stimulation of
      biosynthesis and inhibition of beta-oxidation.
AB  - Lipid accumulation alters macrophage biology and contributes to lipid retention
      within the vessel wall. In this study, we investigated the role of adipophilin on
      triglyceride accumulation and lipid-droplet formation in THP-1-derived
      macrophages (THP-1 macrophages). In the presence of acetylated low-density
      lipoprotein, macrophages infected with an adenovirus expressing human adipophilin
      showed a 31% increase in triglyceride content and a greater number of lipid
      droplets compared with control cells. Incubation of macrophages with very low
      density lipoprotein (VLDL) dramatically increased cellular triglyceride content
      similarly in control and adipophilin-overexpressing cells. By itself, VLDL
      increased adipophilin expression, which explains the lack of effect of
      adipophilin overexpression on cellular triglyceride content in macrophages loaded
      with VLDL. The lipid-droplet content of macrophages was increased by
      overexpression of adipophilin and/or loading with VLDL. In contrast, inhibition
      of adipophilin expression using siRNA prevented lipid-droplet formation and
      significantly reduced intracellular triglyceride content. Using inhibitors of
      beta-oxidation and acyl-coenzyme A synthetase, results were obtained which
      suggest that adipophilin elevates cellular lipids by inhibition of beta-oxidation
      and stimulation of long-chain fatty acid incorporation into triglycerides.
      Adipophilin expression in THP-1 macrophages altered the cellular content of
      different lipids and enhanced the size of lipid droplets, consistent with a role
      for adipophilin in human foam cell formation.

PMID- 16884491
TI  - Growth hormone/JAK-STAT axis signal-transduction defect. A novel treatable cause
      of growth failure.
AB  - Primary cultured fibroblasts of four patients with idiopathic short stature and
      severe growth delay, which displayed normal growth hormone receptor expression
      presented a reduced ability for activation of signal transducer and activator of
      transcription-3 (STAT3). Impaired STAT3 activation was accompanied by cell-cycle
      arrest at the Go /G1 phase. Increased levels of the cyclin-dependent kinase
      inhibitor, p21(WAF/CIPI), and reduced levels of cyclins were also detected in
      these patients. High concentrations of human growth hormone (1000 ng x mL(-1))
      added to the culture medium induced activation of STAT3 and reduced the levels of
      p21(WAF/CIPI) in the fibroblasts of the four idiopathic short stature children.
      Treatment of these children with exogenous human growth hormone significantly
      augmented their growth velocity. Overall, our study provides the first evidence
      linking the idiopathic short stature phenotype with a functional aberration in
      the growth hormone signal transduction cascade which can be successfully overcome
      by exposure to high doses of growth hormone.

PMID- 16884493
TI  - A modelling approach to quantify dynamic crosstalk between the pheromone and the
      starvation pathway in baker's yeast.
AB  - Cells must be able to process multiple information in parallel and, moreover,
      they must also be able to combine this information in order to trigger the
      appropriate response. This is achieved by wiring signalling pathways such that
      they can interact with each other, a phenomenon often called crosstalk. In this
      study, we employ mathematical modelling techniques to analyse dynamic mechanisms
      and measures of crosstalk. We present a dynamic mathematical model that compiles
      current knowledge about the wiring of the pheromone pathway and the filamentous
      growth pathway in yeast. We consider the main dynamic features and the
      interconnections between the two pathways in order to study dynamic crosstalk
      between these two pathways in haploid cells. We introduce two new measures of
      dynamic crosstalk, the intrinsic specificity and the extrinsic specificity. These
      two measures incorporate the combined signal of several stimuli being present
      simultaneously and seem to be more stable than previous measures. When both
      pathways are responsive and stimulated, the model predicts that (a) the
      filamentous growth pathway amplifies the response of the pheromone pathway, and
      (b) the pheromone pathway inhibits the response of filamentous growth pathway in
      terms of mitogen activated protein kinase activity and transcriptional activity,
      respectively. Among several mechanisms we identified leakage of activated Ste11
      as the most influential source of crosstalk. Moreover, we propose new experiments
      and predict their outcomes in order to test hypotheses about the mechanisms of
      crosstalk between the two pathways. Studying signals that are transmitted in
      parallel gives us new insights about how pathways and signals interact in a
      dynamical way, e.g., whether they amplify, inhibit, delay or accelerate each
      other.

PMID- 16884494
TI  - The duality of LysU, a catalyst for both Ap4A and Ap3A formation.
AB  - Heat shock inducible lysyl-tRNA synthetase of Escherichia coli (LysU) is known to
      be a highly efficient diadenosine 5',5'''-P1,P4-tetraphosphate (Ap4A) synthase.
      However, we use an ion-exchange HPLC technique to demonstrate that active LysU
      mixtures actually have a dual catalytic activity, initially producing Ap4A from
      ATP, before converting that tetraphosphate to a triphosphate. LysU appears to be
      an effective diadenosine 5',5'''-P1,P3-triphosphate (Ap3A) synthase. Mechanistic
      investigations reveal that Ap3A formation requires: (a) that the second step of
      Ap4A formation is slightly reversible, thereby leading to a modest reappearance
      of adenylate intermediate; and (b) that phosphate is present to trap the
      intermediate (either as inorganic phosphate, as added ADP, or as ADP generated in
      situ from inorganic phosphate). Ap3A forms readily from Ap4A in the presence of
      such phosphate-based adenylate traps (via a 'reverse-trap' mechanism). LysU is
      also clearly demonstrated to exist in a phosphorylated state that is more
      physically robust as a catalyst of Ap4A formation than the nonphosphorylated
      state. However, phosphorylated LysU shows only marginally improved catalytic
      efficiency. We note that Ap3A effects have barely been studied in prokaryotic
      organisms. By contrast, there is a body of literature that describes Ap3A and
      Ap4A having substantially different functions in eukaryotic cells. Our data
      suggest that Ap3A and Ap4A biosynthesis could be linked together through a single
      prokaryotic dual 'synthase' enzyme. Therefore, in our view there is a need for
      new research into the effects and impact of Ap3A alone and the intracellular
      [Ap3A]/[Ap4A] ratio on prokaryotic organisms.

PMID- 16884495
TI  - Plasmodium falciparum DNA helicase 60. dsRNA- and antibody-mediated inhibition of
      malaria parasite growth and downregulation of its enzyme activities by DNA
      interacting compounds.
AB  - Helicases are ubiquitous enzymes that play important roles in all types of DNA
      transaction in the cells. Recently we have reported the characterization of the
      first DEAD-box helicase [Plasmodium falciparum DNA helicase 60 (PfDH60)] from
      Plasmodium falciparum and have shown that it is a unique, dual bipolar helicase
      expressed in a stage-specific manner. In this study, we show the further
      characterization of PfDH60. For analyzing the significance of this enzyme in
      parasite growth, we studied the effect of dsRNA and specific antibodies on growth
      of the parasite. The studies indicate that the parasite cultures treated with
      PfDH60 dsRNA exhibited approximately 50% growth inhibition when compared with
      either untreated cultures or cultures treated with unrelated dsRNA. It was
      interesting to note that purified immunoglobulins against PfDH60 induced
      approximately 62% inhibition of in vitro growth of P. falciparum and that this
      inhibitory effect was associated with morphologic damage to the parasite. DNA
      interacting compounds inhibit DNA helicase and ssDNA-dependent ATPase activities
      of PfDH60. Of various compounds tested, only actinomycin, daunorubicin, ethidium
      bromide, netropsin and nogalamycin were able to inhibit the enzyme activities of
      PfDH60, with apparent IC50 values for helicase inhibition of 0.8, 0.3, 2.0, 1.2
      and 1.5 microm, respectively. It may be proposed that these compounds form a
      complex with DNA and specifically inhibit helicases due to obstruction in the
      translocation of the enzyme. These compounds also inhibited parasite growth in
      culture. This is the first study to show inhibition of growth of the parasite by
      the dsRNA of a helicase, and most probably this is due to interference with
      cognate mRNA expression.

PMID- 16884496
TI  - Expression and characterization of soluble forms of the extracellular domains of
      the beta, gamma and epsilon subunits of the human muscle acetylcholine receptor.
AB  - The nicotinic acetylcholine receptor (AChR) is a ligand-gated ion channel found
      in muscles and neurons. Muscle AChR, formed by five homologous subunits (alpha2
      beta gamma delta or alpha2 beta gamma epsilon), is the major antigen in the
      autoimmune disease, myasthenia gravis (MG), in which pathogenic autoantibodies
      bind to, and inactivate, the AChR. The extracellular domain (ECD) of the human
      muscle alpha subunit has been heterologously expressed and extensively studied.
      Our aim was to obtain satisfactory amounts of the ECDs of the non-alpha subunits
      of human muscle AChR for use as starting material for the determination of the 3D
      structure of the receptor ECDs and for the characterization of the specificities
      of antibodies in sera from patients with MG. We expressed the N-terminal ECDs of
      the beta (amino acids 1-221; beta1-221), gamma (amino acids 1-218; gamma1-218),
      and epsilon (amino acids 1-219; epsilon1-219) subunits of human muscle AChR in
      the yeast, Pichia pastoris. beta1-221 was expressed at approximately 2 mg.L(-1)
      culture, whereas gamma1-218 and epsilon1-219 were expressed at 0.3-0.8 mg.L(-1)
      culture. All three recombinant polypeptides were glycosylated and soluble; beta1
      221 was mainly in an apparently dimeric form, whereas gamma1-218 and epsilon1-219
      formed soluble oligomers. CD studies of beta1-221 suggested that it has
      considerable beta-sheet secondary structure with a proportion of alpha-helix.
      Conformation-dependent mAbs against the ECDs of the beta or gamma subunits
      specifically recognized beta1-221 or gamma1-218, respectively, and polyclonal
      rabbit antiserum raised against purified beta1-221 bound to (125)I-labeled alpha
      bungarotoxin-labeled human AChR. Moreover, immobilization of each ECD on
      Sepharose beads and incubation of the ECD-Sepharose matrices with MG sera caused
      a significant reduction in the concentrations of autoantibodies in the sera,
      showing specific binding to the recombinant ECDs. These results suggest that the
      expressed proteins present some near-native conformational features and are thus
      suitable for our purposes.

PMID- 16884497
TI  - Patatins, Kunitz protease inhibitors and other major proteins in tuber of potato
      cv. Kuras.
AB  - The major potato tuber proteins of the Kuras cultivar, which is the dominant
      cultivar used in Northern Europe for industrial starch production, were analysed
      using 1D and 2D gel electrophoresis. The electrophoretic patterns varied
      significantly depending on the method of preparation and the potato variant
      (Solanum tuberosum). Proteins were characterized using MS and scored against
      potato protein databases, derived from both 'Kuras only' and 'all potato'
      expressed sequence tags (EST) and full-length cDNAs. Despite the existence of
      approximately 180 000 ESTs, the currently available potato sequence data showed a
      severe under-representation of genes or long transcripts encoding proteins > 50
      kDa (3.5% of all) compared with the complete proteome of Arabidopsis thaliana
      (33% of all). We found that patatin and Kunitz protease inhibitor (KPI) variants
      are extraordinarily dominant in Kuras tuber and, most significantly, that their
      amino acid sequences are specific to Kuras. Other proteins identified include
      annexin, glyoxalase I, enolase and two lipoxygenases, the sequences of which are
      highly conserved among potato variants. Known S. tuberosum patatins cluster into
      three clades all represented in Kuras. S. tuberosum KPIs cluster into more
      diverse clades of which five were found in Kuras tuber, including a novel clade,
      KPI K, found to date only in Kuras. Furthermore, protein abundance was contrasted
      with the levels of corresponding gene transcripts found in our previous EST and
      LongSAGE studies of Kuras tuber.

PMID- 16884498
TI  - Voltage- and Ca2+-activated potassium channels in Ca2+ store control Ca2+
      release.
AB  - Ca2+ release from Ca2+ stores is a 'quantal' process; it terminates after a rapid
      release of stored Ca2+. To explain the quantal nature, it has been supposed that
      a decrease in luminal Ca2+ acts as a 'brake' on store release. However, the
      mechanism for the attenuation of Ca2+ efflux remains unknown. We show that Ca2+
      release is controlled by voltage- and Ca2+-activated potassium channels in the
      Ca2+ store. The potassium channel was identified as the big or maxi-K (BK)-type,
      and was activated by positive shifts in luminal potential and luminal Ca2+
      increases, as revealed by patch-clamp recordings from an exposed nuclear
      envelope. The blockage or closure of the store BK channel due to Ca2+ efflux
      developed lumen-negative potentials, as revealed with an organelle-specific
      voltage-sensitive dye [DiOC5(3); 3,3'-dipentyloxacarbocyanine iodide], and
      suppressed Ca2+ release. The store BK channels are reactivated by Ca2+ uptake by
      Ca2+ pumps regeneratively with K+ entry to allow repetitive Ca2+ release. Indeed,
      the luminal potential oscillated bistably by approximately 45 mV in amplitude.
      Our study suggests that Ca2+ efflux-induced store BK channel closures attenuate
      Ca2+ release with decreases in counter-influx of K+.

PMID- 16884499
TI  - A kinetic study of a ternary cycle between adenine nucleotides.
AB  - In the present paper, a kinetic study is made of the behavior of a moiety
      conserved ternary cycle between the adenine nucleotides. The system contains the
      enzymes S-acetyl coenzyme A synthetase, adenylate kinase and pyruvate kinase, and
      converts ATP into AMP, then into ADP and finally back to ATP. L-Lactate
      dehydrogenase is added to the system to enable continuous monitoring of the
      progress of the reaction. The cycle cannot work when the only recycling substrate
      in the reaction medium is AMP. A mathematical model is proposed whose kinetic
      behavior has been analyzed both numerically by integration of the nonlinear
      differential equations describing the kinetics of the reactions involved, and
      analytically under steady-state conditions, with good agreement with the
      experimental results being obtained. The data obtained showed that there is a
      threshold value of the S-acetyl coenzyme A synthetase/adenylate kinase ratio,
      above which the cycle stops because all the recycling substrate has been
      accumulated as AMP, never reaching the steady state. In addition, the concept of
      adenylate energy charge has been applied to the system, obtaining the enabled
      values of the rate constants for a fixed adenylate energy charge value and vice
      versa.

PMID- 16884500
TI  - The aggregation potential of human amylin determines its cytotoxicity towards
      islet beta-cells.
AB  - Human amylin is a small fibrillogenic protein that is the major constituent of
      pancreatic islet amyloid, which occurs in most subjects with type 2 diabetes.
      There is evidence that it can elicit in vitro apoptosis in islet beta-cells, but
      the physical properties that underpin its cytotoxicity have not been clearly
      elucidated. Here we employed electron microscopy, thioflavin T fluorescence and
      CD spectroscopy to analyze amylin preparations whose cytotoxic potential was
      established by live-dead assay in cultured beta-cells. Highly toxic amylin
      contained few preformed fibrils and initially showed little beta-sheet content,
      but underwent marked time-dependent aggregation and beta-conformer formation
      following dissolution. By contrast, low-toxicity amylin contained abundant
      preformed fibrils, and demonstrated high initial beta-sheet content but little
      propensity to aggregate further once dissolved. Thus, mature amylin fibrils are
      not toxic to beta-cells, and aggregates of fibrils such as occur in pancreatic
      islet amyloid in vivo are unlikely to contribute to beta-cell loss. Rather, the
      toxic molecular species is likely to comprise soluble oligomers with significant
      beta-sheet content. Attempts to find ways of protecting beta-cells from amylin
      mediated death might profitably focus on preventing the conformational change
      from random coil to beta-sheet.

PMID- 16884501
TI  - Agrobacterium tumefaciens type II NADH dehydrogenase. Characterization and
      interactions with bacterial and thylakoid membranes.
AB  - Type II NADH dehydrogenases (NDH-2) are monomeric enzymes that catalyse quinone
      reduction and allow electrons to enter the respiratory chain in different
      organisms including higher plant mitochondria, bacteria and yeasts. In this
      study, an Agrobacterium tumefaciens gene encoding a putative alternative NADH
      dehydrogenase (AtuNDH-2) was isolated and expressed in Escherichia coli as a
      (His)6-tagged protein. The purified 46 kDa protein contains FAD as a prosthetic
      group and oxidizes both NADH and NADPH with similar Vmax values, but with a much
      higher affinity for NADH than for NADPH. AtuNDH-2 complements the growth (on a
      minimal medium) of an E. coli mutant strain deficient in both NDH-1 and NDH-2,
      and is shown to supply electrons to the respiratory chain when incubated with
      bacterial membranes prepared from this mutant. By measuring photosystem II
      chlorophyll fluorescence on thylakoid membranes prepared from the green alga
      Chlamydomonas reinhardtii, we show that AtuNDH-2 is able to stimulate NADH
      dependent reduction of the plastoquinone pool. We discuss the possibility of
      using heterologous expression of NDH-2 enzymes to improve nonphotochemical
      reduction of plastoquinones and H2 production in C. reinhardtii.

PMID- 16884502
TI  - Upgrading pacing generators in the era of biventricular pacing.

PMID- 16884503
TI  - Upgrading of VVIR pacemakers with nonfunctional endocardial ventricular leads to
      VDD pacemakers in adolescents.
AB  - BACKGROUND: In some children with ventricular rate responsive demand (VVIR)
      pacemakers (PM), transvenous leads fail for technical reasons or patient's
      growth. AIM: The aim of this study is to describe our experience in adolescents
      with a nonfunctional ventricular lead in whom the lead was abandoned and an
      additional VDD lead was implanted. Of the 136 children who received a VVIR PM
      with an endocardial lead in our center, seven patients aged 7 (0.3-12) years
      [median (range)] at initial implantation, after 10 (5-15) years showed lead
      malfunction and underwent atrial synchronous ventricular inhibited pacing (VDD)
      PM upgrading at 16 (10-20) years. RESULTS: The VDD lead was inserted through the
      ipsilateral subclavian vein in five patients, the contralateral in two (venous
      occlusion in one and for operator choice in the first patient). The tip was
      positioned into the right ventricular apex, the atrial dipole along the lateral
      atrial wall. Fluoroscopy times were not significantly different from those
      measured in SSI PM implantation and in VVIR dual-chamber demand pacing (VVIR-DDD)
      upgrading. There were no intraprocedural complications. Follow-up duration is 12
      (6-62) months. The VDD PM showed good function, no undersensing or oversensing.
      Tricuspid damage, new venous occlusion, and "twisting" of the two leads at x-ray
      were not documented. The first patient showed an infection of the old PM pocket
      after 1 year, local pain after 3 years, and endocarditis of the leads after 5
      years. CONCLUSION: The upgrading of VVIR PM to VDD PM with the abandonment of the
      nonfunctional lead is feasible, with no intraprocedural complications and good PM
      function. Lead endocarditis occurred in one patient.

PMID- 16884504
TI  - Reducing unnecessary right ventricular pacing with the managed ventricular pacing
      mode in patients with sinus node disease and AV block.
AB  - BACKGROUND: Frequent and unnecessary right ventricular apical pacing increases
      the risk of atrial fibrillation or congestive heart failure. We evaluated a new
      pacing algorithm, managed ventricular pacing (MVP) which automatically changes
      modes between AAI/R and DDD/R in patients receiving pacemakers for symptomatic
      bradycardia. METHODS: Patients were randomized to the MVP mode or DDD/R mode for
      1 month and then crossed over to the alternate pacing modality for an additional
      month. On completion of the crossover phase, the pacing mode selected was
      individualized and patients were followed for an additional 4 months. RESULTS: Of
      the 129 patients who successfully completed the crossover study, the cumulative
      percent ventricular pacing was significantly reduced in the MVP mode (median
      1.4%) compared to the DDD/R mode (median 89.6%, 94.0% relative reduction; 95% CI
      89.3-98.8%, P < 0.001). Patients with sinus node disease (SND, n = 51) when
      compared to patients with AV block (AVB) (n = 68) experienced a greater reduction
      in ventricular pacing with the MVP mode compared to the DDD/R mode (median
      relative reduction 99.1%; 95% CI 97.5-99.9% vs median relative reduction 60.1%;
      95% CI 16.7-93.9% P < 0.001). The reduced percent ventricular pacing during MVP
      was sustained over longer term follow-up. CONCLUSIONS: The majority of patients
      with a bradycardia indication for cardiac pacing do not require ventricular
      pacing most of the time. The MVP mode significantly reduces unnecessary right
      ventricular pacing. This mode benefits even patients with intermittent AVB and is
      sustained over longer term follow-up.

PMID- 16884505
TI  - Ultrasonographic predictors of unsuccessful cephalic vein approach during
      pacemaker or defibrillator lead implantation.
AB  - BACKGROUND: The cephalic vein approach is a preferred route for endocardial lead
      implantation; however, it is associated with a significant failure rate. Anatomic
      abnormalities likely play an important role, but specific features have not been
      well characterized. METHODS: Color Doppler ultrasonography was performed in 82
      consecutive patients prior to endocardial lead implantation. Venous diameter,
      depth, flow velocity, and morphology were evaluated and comparisons made between
      the successful and failed implantations at various stages of the procedure.
      RESULTS: Endocardial lead implantation was unsuccessful in 14 patients (17%),
      with eight patients of venous isolation failure, 4 patients of cannulation
      failure, and 2 patients of guidewire crossing failure. Venous diameter was found
      to be the only independent predictor for isolation and implantation failure. The
      best cutoff value of cephalic venous diameter to predict unsuccessful cephalic
      venous approach was < or = 2.2 mm. In total, there were 10 patients with
      extensive cephalic vein tortuosity. In seven of these 10 patients, the incidence
      of standard guidewire crossing failure was significantly higher than that without
      a tortuous cephalic vein (7/10 vs 6/60, P < 0.001). After switching to a
      hydrophilic guidewire, crossing and navigation were successful in five of the
      seven patients. CONCLUSIONS: Color Doppler imaging is useful to identify cephalic
      vein characteristics. A small venous diameter is the ultrasonographic predictor
      for failure of cephalic vein approach. A tortuous venous morphology is associated
      with a high incidence of guidewire crossing failure, which can be mostly overcome
      by using a hydrophilic guidewire.

PMID- 16884506
TI  - Clinical study of amiodarone-associated torsade de pointes in Chinese people.
AB  - OBJECTS: Amiodarone-associated torsade de pointes (Tdp) has been reported
      increasingly in China in recent years. In this study, we made clinical analysis
      of amiodarone-associated Tdp in Chinese people. METHODS: Two major Chinese
      medical databases were searched to identify articles published during the last 26
      years that presented data on amiodarone-associated proarrhythmic events. The
      articles were divided into two categories: case reports and observational
      studies. RESULTS: Fifty-two Chinese-language case reports with 98 patients and 2
      patients registered in our hospital, total 100 patients about amiodarone
      associated Tdp, were enrolled in the study. Amiodarone-associated Tdp occurred
      more frequently in females (68.0%, 68/100). The major primary disease of females
      was rheumatic heart disease (40.7%, 24/59), while that of males was coronary
      heart disease (45.8%, 11/24). In most patients, Tdp occurred repeatedly and
      terminated in 24-48 hours. Some Tdp worsen to ventricular fibrillation and caused
      19 patients' death (mortality rate 21.8%, 19/87). Known predisposing factors to
      the development of Tdp, such as heart failure, hypokalemia, drugs combination,
      and bradyarrhythmia, existed in many cases. Tdp also occurred in six patients (4
      females, 2 males) without any known predisposing factors except QTc interval
      prolongation. Fourteen observational studies each reported data from at least 100
      patients who were treated with amiodarone for at least 1 month. Of 2,354 patients
      included in these studies, 455 patients exposed to amiodarone were reported to
      have proarrhythmic events (an overall incidence of 19.3%), while only 4 patients
      were reported to have Tdp or ventricular fibrillation (an incidence of 0.17%).
      CONCLUSIONS: In conclusion, approximately one-fifth of the patients have
      amiodarone-induced proarrhythmic events, while the incidence of Tdp or
      ventricular fibrillation is remarkably low. Amiodarone-associated Tdp occurred
      more frequently in Chinese females. Known predisposing factors for occurrence of
      Tdp prevailed in Chinese patients. QTc interval prolongation may be an
      independent risk factor of amiodarone-associated Tdp.

PMID- 16884508
TI  - The risk profile for obstructive sleep apnea does not affect the recurrence of
      atrial fibrillation.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) has been linked to increased prevalence
      and recurrence of atrial fibrillation (AF). We hypothesized that OSA may
      aggravate AF in patients with pacemakers implanted for sinus bradycardia who had
      documented paroxysmal AF. METHODS: Seventy-two patients (36 M, aged 77 +/- 6
      years) completed the study. All patients received a dual-chamber pacemaker
      equipped with diagnostic and preventive functions for AF. OSA was diagnosed with
      the Berlin Questionnaire, which is validated to identify patients with OSA. Four
      month continuous pacemaker recordings were collected for all patients. RESULTS:
      OSA was diagnosed in 28% of patients. Patients at high risk for OSA (HR group)
      and patients at low risk for OSA (LR group) were equivalent for gender, age, and
      body mass index. The rate of hypertension was higher in HR than in LR group (90%
      vs 44%, P < 0.01). The prevalence of paroxysmal AF during the study period was
      similar in HR and LR group (53% vs 44%, P = NS). Overall number of AF episodes
      per month was not significantly different between HR and LR group (7 +/- 13 vs 36
      +/- 122, P = NS). Similarly, AF burden (AF%) was not significantly different
      between HR and LR group (0.3 +/- 0.6 vs 2.0 +/- 4.8, P = NS). Circadian
      distribution of AF episodes was similar in both groups. CONCLUSION: Long-term
      pacemaker recording of AF recurrence, AF burden, and its circadian distribution
      is similar in patients with paroxysmal AF at high risk for OSA and those at low
      risk for OSA.

PMID- 16884507
TI  - The superior transseptal surgical approach to mitral valve creates slow
      conduction.
AB  - BACKGROUND: Atrial tachycardia is very frequent after mitral valve surgery using
      the superior transseptal approach. METHODS: Sixteen patients operated on for
      mitral valve disease (superior transseptal approach = Group A, n = 9, and left
      atrial approach = Group B, n = 7) underwent radiofrequency catheter ablation of
      atrial tachycardia guided by electroanatomic mapping. Twenty-six consecutive
      patients without previous cardiac surgery with typical atrial flutter served as
      controls (Group C). RESULTS: Atrial tachycardia occurred earlier after the
      operation in Group A than in Group B (median 97 vs 2,159 days, P = 0.003).
      Typical atrial flutter was the most frequent circuit in all groups (Group A-7
      patients, Group B-5 patients, Group C-26 patients). Three patients in Group A
      developed right atrial incisional tachycardia. Ten of 14 tachycardia circuits
      (typical atrial flutter, n = 7, incisional tachycardia, n = 3) in Group A
      depended on the corridor between the right atrial part of the atriotomy and the
      tricuspid annulus. Slow conduction during typical atrial flutter was detected in
      this corridor in Group A, but not in the corresponding region in Groups B and C
      (P < 0.001). The cycle length of typical atrial flutter was longer in Groups A
      and B than in Group C (mean 283 ms and 282 ms vs 233 ms, P = 0.003). Patients in
      Group B with typical atrial flutter had larger right atria than patients in Group
      A or Group C (mean 156 mL vs 96 mL and 113 mL, P = 0.033). CONCLUSIONS: The
      superior transseptal incision may predispose to atrial tachycardia by creating
      slow conduction between the atriotomy and the tricuspid annulus.

PMID- 16884509
TI  - Microvolt t-wave alternans with exercise in pediatrics and congenital heart
      disease: limitations and predictive value.
AB  - BACKGROUND: Microvolt t-wave alternans (TWA) in early exercise is a noninvasive
      marker of life-threatening ventricular arrhythmia in some adult cardiac
      populations. The incidence and potential significance of sustained TWA in
      pediatric and congenital heart disease (CHD) populations has not been well
      defined. METHODS: TWA treadmill exercise studies in pediatric patients with CHD,
      myopathy, potential myocardial ischemia, syncope, or history of cardiac arrest
      were analyzed. Tests were categorized as abnormal for sustained TWA with onset
      heart rate < 130 beats/min with specific analyses for lower onset heart rates.
      Patient characteristics were analyzed as possible correlates of TWA. RESULTS:
      Over 2 years, 318 consecutive TWA exercise studies were performed in 304 patients
      (60% male, median 14 years, 6-41) for indications of syncope, cardiac arrest,
      possible ventricular arrhythmia, or evaluation of functional myocardial
      perfusion. Underlying conditions included apparently normal hearts (45%), CHD
      (16%), cardiomyopathy (11%), coronary anomalies (11%), electrical myopathy (9%),
      and transplant (8%). Abnormal TWA was seen in 24 (7%, onset HR 106 +/- 18) and
      included 19 at high clinical risk for serious events including 3 with cardiac
      arrest. By multivariate analysis sustained TWA was associated with cardiac
      arrest, ventricular arrhythmias, and a clinical classification of high risk.
      CONCLUSIONS: TWA is associated with pediatric and CHD diagnoses at high risk of
      serious events and may contribute, with other diagnostic tools, to management
      choices. While the absence of TWA has relatively high negative predictive value,
      it does not completely exclude the potential for serious sustained ventricular
      arrhythmias. A more robust noninvasive marker for risk stratification in these
      populations is required.

PMID- 16884510
TI  - Dynamic changes of P-wave duration and P-wave axis during head-up tilt test in
      patients with vasovagal syncope.
AB  - BACKGROUND: The exact role of venous pooling in the pathogenesis of vasovagal
      syncope (VVS) is not fully elucidated. P-wave duration on an electrocardiogram
      can serve as a measure of atrial volume. METHODS: Sixty-six patients (15 men, 51
      women, mean age 32 years) with unexplained syncope were enrolled in the study.P
      wave duration and the P-wave axis (PWA) were measured during passive head-up tilt
      test (HUT) in order to evaluate dynamic changes of atrial filling in patients
      with VVS. RESULTS: HUT was positive in 40 patients (6 men, 34 women, mean age 32
      +/- 9 years) and negative in 26 patients (9 men, 17 women, mean age 33 +/- 8
      years). The P-wave duration was significantly reduced in HUT-positive patients at
      the onset of symptoms as compared to 5 minutes (88.8 +/- 11.9 vs 96.2 +/- 12.0
      ms, P = 0.008), and baseline (88.8 +/- 11.9 vs 96.8 +/- 13.8 ms, P = 0.005). The
      P-wave duration was significantly shorter at the onset of presyncope in HUT
      positive patients as compared to HUT-negative patients (88.8 +/- 11.9 vs 100.3 +/
      11.2 ms, P = 0.0002). In HUT-positive patients, a significant increase in PWA
      was found at the onset of symptoms when compared to baseline (67.7 +/- 22.1
      degrees vs 47.9 +/- 14.9 degrees, P < 0.0001) and 5 minutes of HUT (67.7 +/- 22.1
      degrees vs 54.4 +/- 14.9 degrees, P = 0.005). At the time of syncope, PWA was
      more inferior in HUT-positive patients than in HUT-negative patients (67.7 +/-
      22.1 degrees vs 51.8 +/- 13.8 degrees, P = 0.015). CONCLUSIONS: VVS is associated
      with the reduction in P-wave duration and the increase in PWA, which can be a
      result of exaggerated venous pooling and reduction in atrial volume.

PMID- 16884511
TI  - Effects of angiotensin converting enzyme inhibitor and angiotensin II receptor
      blocker on ventricular defibrillation threshold.
AB  - BACKGROUND: Angiotensin converting enzyme (ACE) inhibitors and Angiotensin II
      (AII) receptor blockers have previously been shown to be beneficial in treating
      patients with not only hypertension but also with cardiovascular diseases.
      Therefore, such drugs may potentially be used in patients with an implantable
      cardioverter defibrillator (ICD) who show cardiac dysfunctions. OBJECTIVE: This
      study aimed to determine effects of short-term administration of the ACE
      inhibitor (CV-3317) and the AII receptor blocker (CV-11974, an active form of
      candesartan) on internal defibrillation threshold (DFT) in anesthetized canine
      hearts. METHODS: DFTs were evaluated using a "hot can" defibrillation lead system
      in: (a) seven dogs following three intravenous administrations of 20 cc saline;
      (b) 11 dogs that received intravenous CV-3317 doses of 1 mg/kg, 10 mg/kg, and 50
      mg/kg; and in (c) 10 dogs that were intravenously given 0.1 mg/kg, 1 mg/kg, and
      10 mg/kg CV-11974. DFTs were determined using a "down-up down-up" protocol.
      RESULTS: Mean DFT delivered energies at baseline and following three consecutive
      intravenous saline injections were 16.4 +/- 9.3 J, 15.3 +/- 7.5 J, 15.9 +/- 7.1
      J, and 15.5 +/- 5.6 J, respectively. Those at baseline and following 1 mg/kg, 10
      mg/kg, and 50 mg/kg intravenous CV-3317 were 12.9 +/- 6.4 J, 12.2 +/- 6.4 J, 11.0
      +/- 6.6 J, and 11.9 +/- 6.6 J, respectively. Similarly, those at baseline and
      after 0.1 mg/kg, 1 mg/kg, and 10 mg/kg CV-11974 were 13 +/- 6.6 J, 12.5 +/- 6 J,
      12.9 +/- 5.8 J, and 13.2 +/- 6.6 J, respectively. There were no significant
      differences between DFT at baseline and the others in each treatment group.
      CONCLUSIONS: Since an ACE inhibitor and an AII receptor blocker did not alter
      DFT, such drugs may be useful in ICD patients without a decrease in safety
      margins.

PMID- 16884512
TI  - Anti-inflammatory effect of cardiac resynchronization therapy.
AB  - BACKGROUND: Congestive heart failure (CHF) is associated with persistent immune
      activation. Medical therapy has been shown to exert only limited anti
      inflammatory effects. Cardiac resynchronization therapy (CRT) reduces morbidity
      and mortality in a subset of patients with heart failure, but it is not known
      whether this treatment affects the immune system as well. To test this
      hypothesis, eight patients with heart failure scheduled for CRT were investigated
      for immune activation before and 6 months after CRT treatment. METHODS AND
      RESULTS: After 6 months, all patients had improved in NYHA-class and LVEF, and
      there was a statistically significant reduction in serum N-terminal pro brain
      natriuretic peptide (BNP). Furthermore, there was a statistically significant
      reduction in plasma levels of the chemokines monocyte chemoattractant protein 1
      (MCP-1) and interleukin 8 (IL-8) and the cytokine interleukin 6 (IL-6). We
      observed no changes in the levels of interleukin 1beta (IL-1beta), tumor necrosis
      factor alpha (TNF-alpha), interleukin 10 (IL-10), or complement activation
      products. There was a significant correlation between changes in BNP and IL-6 (r
      = 0.74, P = 0.037). CONCLUSION: Although based upon a limited number of patients,
      this report indicates that CRT reduces peripheral markers of immune activation in
      patients with CHF. Further large scale studies are warranted to verify these
      findings.

PMID- 16884513
TI  - Antitachycardia pacing for spontaneous rapid ventricular tachycardia in patients
      with prophylactic cardioverter-defibrillator therapy.
AB  - AIMS: Antitachycardia pacing (ATP) has not routinely been used in patients who
      received implantable cardioverter defibrillators (ICDs) for primary prevention of
      sudden death. This study investigated the efficacy of empirical ATP to terminate
      rapid ventricular tachycardia (VT) in heart failure patients with prophylactic
      ICD therapy. METHODS AND RESULTS: Ninety-three patients with a mean left
      ventricular ejection fraction of 22 +/- 7% (range: 9-35%) due to nonischemic or
      ischemic cardiomyopathy received prophylactic ICDs with empiric ATP. At least 2
      ATP sequences with 6-pulse burst pacing trains at 81% of VT cycle length (CL)
      were programmed in one or two VT zones for CL below 335 +/- 23 ms and above 253
      +/- 18 ms. Ventricular flutter and fibrillation (VF) with CL below 253 +/- 18 ms
      were treated in a separate VF zone with ICD shocks without preceding ATP
      attempts. During 38 +/- 27 months follow-up, 339 spontaneous ventricular
      tachyarrhythmias occurred in 36 of 93 study patients (39%). A total of 232 VT
      episodes, mean CL 293 +/- 22 ms, triggered ATP in 25 of 36 patients with ICD
      interventions (69%). ATP terminated 199 of 232 VT episodes (86%) with a mean CL
      of 294 +/- 23 ms in 23 of 25 patients (88%) who received ATP therapy. ATP failed
      to terminate or accelerated 33 of 232 VT episodes (14%) with a mean CL of 287 +/-
      19 ms in 12 of 25 patients (48%) who received ATP therapy. CONCLUSIONS: Painfree
      termination of rapid VT with empirical ATP is common in heart failure patients
      with prophylactic ICD therapy. The occasional inability of empiric ATP to
      terminate rapid VT in almost 50% of patients who receive ATP for rapid VT
      warrants restrictive ICD programming with regard to the number of ATP attempts in
      order to avoid syncope before VT termination occurs.

PMID- 16884514
TI  - Isorhythmic dissociation with smart sensing in a dual-chamber implantable
      cardioverter defibrillator.
AB  - Isorhythmic dissociation is an uncommon but clinically important finding in a
      patient implanted with a dual chamber cardioverter defibrillator (ICD) capable of
      SmartSensing. The surface ECG mimicked a malfunction of the pacemaker that was
      related to the concomitant hemodynamic deterioration. Device interrogation
      revealed dissociation of the intrinsic junctional and the pacemaker rhythm, which
      appeared at similar rates. Careful analysis of intracardiac electrograms and
      marker channel annotations helped to unravel the limitations for physiologic
      pacing.

PMID- 16884515
TI  - Focal atrial tachycardia II: management.
AB  - Over the last decade there have been significant changes in the treatment of
      focal atrial tachycardia (AT). This review concentrates on the different
      approaches to the treatment of focal AT. Initial therapies included
      antiarrhythmic medications and surgery. However, with the advent of
      radiofrequency ablation, and the poor efficacy of pharmacological therapy, there
      has been a shift toward a primary ablative approach. Several different mapping
      techniques have been proposed. The different techniques, including P-wave
      morphology and advanced three-dimensional mapping, are discussed in this review.

PMID- 16884517
TI  - Pulmonary arterial embolization of pacemaker lead electrode tip.
AB  - Complications with extraction of abundant endovascular systems increase with time
      since implantation. As the number of implanted devices increases, successful
      management of complications needs to be disseminated. We present a 46-year-old
      woman with endovascular leads placed 15 years previously requiring extraction.
      Using laser-assistance the leads were removed, although the passive lead tips
      were unable to be extracted, and were retained in the superior vena cava. One
      lead tip embolized to the distal pulmonary bed within 24 hours of her operative
      procedure. Computed tomography and pulmonary arteriography suggested a near
      immediate thrombogenic process. A multidisciplinary approach was utilized to
      identify management strategies that allowed for a satisfactory patient outcome.

PMID- 16884516
TI  - Biventricular pacing using dual-site right ventricular stimulation: is it placebo
      effect?
AB  - Alternate site lead placement in cardiac resynchronization therapy has been used
      successfully but remains to be validated. A 62-year-old heart failure patient in
      whom coronary sinus lead placement was not possible underwent implantation of the
      lead in the right ventricular outflow tract (RVOT) and demonstrated clinical
      improvement as measured by New York Heart Association class and noninvasive
      parameters. When heart failure recurred, it was determined that his RVOT
      electrode had been pulled back (Twiddler's syndrome). Repositioning again
      improved his clinical status and noninvasive hemodynamic measurements. With dual
      site right ventricular (RV) pacing there was no echocardiographic measurable
      intraventricular dyssynchrony. Tissue Doppler imaging correlated with clinical
      improvement using dual-site RV pacing, providing evidence that this technique may
      represent a viable alternative in cardiac resynchronization therapy.

PMID- 16884518
TI  - A grave case of bradycardia.
AB  - Tachycardia is a prominent feature of thyrotoxicosis. We present an unusual case
      of Graves' thyrotoxicosis presenting as profound symptomatic bradycardia.

PMID- 16884519
TI  - Idiopathic polymorphic ventricular tachycardia with normal QT interval in a
      structurally normal heart.
AB  - Polymorphic ventricular tachycardia (PVT) is a life-threatening arrhythmia that
      is typically related to long QT syndrome, organic heart disease, electrolyte
      abnormalities, cardiotoxic drugs, or adrenergic stimulation. A review of the
      literature reveals that PVT with normal QT interval and without underlying cause
      is quite rare. We report a case of idiopathic spontaneous PVT with structurally
      normal heart and without electrolyte abnormalities, drug reactions, or evidence
      of catecholamine induced arrhythmia. We also review the literature on the
      electrocardiographic characteristics and management of idiopathic PVT.

PMID- 16884520
TI  - Epicardial ablation of ventricular tachycardia associated with isolated
      ventricular noncompaction.
AB  - A 52-year-old man presented with sudden onset of palpitations and dizziness.
      Echocardiogram confirmed the diagnosis of isolated noncompaction of ventricular
      myocardium with moderated systolic dysfunction, and the electrocardiogram (ECG)
      revealed ventricular tachycardia (VT), of which the focus seemed to match an area
      of prominent left ventricular noncompaction on the 12-lead surface ECG. Through
      the activation mapping from the endo- and epicardium, simultaneously, a discrete
      potential preceding the QRS during VT was observed at the anterolateral
      epicardial wall. He subsequently underwent radiofrequency ablation, and VT was
      successfully eliminated.

PMID- 16884521
TI  - Reproducibility of T-wave alternans in congestive heart failure: a theoretical
      argument.

PMID- 16884523
TI  - Elegant study performed to assess the early impaired autonomic function in HIV
      infected subjects.

PMID- 16884525
TI  - Primate-specific evolution of an LDLR enhancer.
AB  - BACKGROUND: Sequence changes in regulatory regions have often been invoked to
      explain phenotypic divergence among species, but molecular examples of this have
      been difficult to obtain. RESULTS: In this study we identified an anthropoid
      primate-specific sequence element that contributed to the regulatory evolution of
      the low-density lipoprotein receptor. Using a combination of close and distant
      species genomic sequence comparisons coupled with in vivo and in vitro studies,
      we found that a functional cholesterol-sensing sequence motif arose and was fixed
      within a pre-existing enhancer in the common ancestor of anthropoid primates.
      CONCLUSION: Our study demonstrates one molecular mechanism by which ancestral
      mammalian regulatory elements can evolve to perform new functions in the primate
      lineage leading to human.

PMID- 16884526
TI  - Combinatorial RNA interference in Caenorhabditis elegans reveals that redundancy
      between gene duplicates can be maintained for more than 80 million years of
      evolution.
AB  - BACKGROUND: Systematic analyses of loss-of-function phenotypes have been carried
      out for most genes in Saccharomyces cerevisiae, Caenorhabditis elegans, and
      Drosophila melanogaster. Although such studies vastly expand our knowledge of
      single gene function, they do not address redundancy in genetic networks.
      Developing tools for the systematic mapping of genetic interactions is thus a key
      step in exploring the relationship between genotype and phenotype. RESULTS: We
      established conditions for RNA interference (RNAi) in C. elegans to target
      multiple genes simultaneously in a high-throughput setting. Using this approach,
      we can detect the great majority of previously known synthetic genetic
      interactions. We used this assay to examine the redundancy of duplicated genes in
      the genome of C. elegans that correspond to single orthologs in S. cerevisiae or
      D. melanogaster and identified 16 pairs of duplicated genes that have redundant
      functions. Remarkably, 14 of these redundant gene pairs were duplicated before
      the divergence of C. elegans and C. briggsae 80-110 million years ago, suggesting
      that there has been selective pressure to maintain the overlap in function
      between some gene duplicates. CONCLUSION: We established a high throughput method
      for examining genetic interactions using combinatorial RNAi in C. elegans. Using
      this technique, we demonstrated that many duplicated genes can retain redundant
      functions for more than 80 million years of evolution. This provides strong
      support for evolutionary models that predict that genetic redundancy between
      duplicated genes can be actively maintained by natural selection and is not just
      a transient side effect of recent gene duplication events.

PMID- 16884527
TI  - Statistical assessment of the global regulatory role of histone acetylation in
      Saccharomyces cerevisiae.
AB  - BACKGROUND: Histone acetylation plays important but incompletely understood roles
      in gene regulation. A comprehensive understanding of the regulatory role of
      histone acetylation is difficult because many different histone acetylation
      patterns exist and their effects are confounded by other factors, such as the
      transcription factor binding sequence motif information and nucleosome occupancy.
      RESULTS: We analyzed recent genomewide histone acetylation data using a few
      complementary statistical models and tested the validity of a cumulative model in
      approximating the global regulatory effect of histone acetylation. Confounding
      effects due to transcription factor binding sequence information were estimated
      by using two independent motif-based algorithms followed by a variable selection
      method. We found that the sequence information has a significant role in
      regulating transcription, and we also found a clear additional histone
      acetylation effect. Our model fits well with observed genome-wide data.
      Strikingly, including more complicated combinatorial effects does not improve the
      model's performance. Through a statistical analysis of conditional independence,
      we found that H4 acetylation may not have significant direct impact on global
      gene expression. CONCLUSION: Decoding the combinatorial complexity of histone
      modification requires not only new data but also new methods to analyze the data.
      Our statistical analysis confirms that histone acetylation has a significant
      effect on gene transcription rates in addition to that attributable to upstream
      sequence motifs. Our analysis also suggests that a cumulative effect model for
      global histone acetylation is justified, although a more complex histone code may
      be important at specific gene loci. We also found that the regulatory roles among
      different histone acetylation sites have important differences.

PMID- 16884528
TI  - The geographic distribution of melanoma incidence in Massachusetts, adjusted for
      covariates.
AB  - BACKGROUND: The aims of this study were to determine whether observed geographic
      variations in melanoma cancer incidence in both gender groups are simply random
      or are statistically significant, whether statistically significant excesses are
      temporary or persistent, and whether they can be explained by risk factors such
      as socioeconomic status (SES) or the percent of the population residing in an
      urban rather than a rural area. Between 1990 and 1999, 4774 female and 5688 male
      melanomas were diagnosed in Massachusetts residents. Cases were aggregated to
      census tracts and analyzed for deviations from random occurrence with respect to
      both spatial location and time. RESULTS: Thirteen geographic areas that deviated
      significantly from randomness were uncovered in the age-adjusted analyses of
      males: five with higher incidence rates than expected and eight lower than
      expected. In the age-adjusted analyses of females, six areas with higher
      incidence rates and eight areas with lower than expected incidence rates were
      found. After adjustment for SES and percent urban, several of these areas were no
      longer significantly different. CONCLUSION: These analyses identify geographic
      areas with invasive melanoma incidence higher or lower than expected, the times
      of their excess, and whether or not their status is affected when the model is
      adjusted for risk factors. These surveillance findings can be a sound starting
      point for the shoe-leather epidemiologist.

PMID- 16884529
TI  - Prediction of a key role of motifs binding E2F and NR2F in down-regulation of
      numerous genes during the development of the mouse hippocampus.
AB  - BACKGROUND: We previously demonstrated that gene expression profiles during
      neuronal differentiation in vitro and hippocampal development in vivo were very
      similar, due to a conservation of the important second singular value
      decomposition (SVD) mode (Mode 2) of expression. The conservation of Mode 2
      suggests that it reflects a regulatory mechanism conserved between the two
      systems. In either dataset, the expression vectors of all the genes form two
      large clusters that differ in the sign of the contribution of Mode 2, which for
      the majority of them reflects the difference between down- or up-regulation.
      RESULTS: In the current work, we used a novel approach of analyzing cis
      regulation of gene expression in a subspace of a single SVD mode of temporal
      expression profiles. In the putative upstream regulatory sequences identified by
      mouse-human homology for all the genes represented in either dataset, we searched
      for simple features (motifs and pairs of motifs) associated with either sign of
      the loading of Mode 2. Using a cross-system training-test set approach, we
      identified E2F binding sites as predictors of down-regulation of gene expression
      during hippocampal development. NR2F binding sites, for the transcription factors
      Nr2f/COUP and Hnf4, and also NR2F_SP1 pairs of binding sites, were predictors of
      down-regulation of expression both during hippocampal development and neuronal
      differentiation. Analysis of another dataset, from gene profiling of myoblast
      differentiation in vitro, shows that the conservation of Mode 2 extends to the
      differentiation of mesenchymal cells. This permitted the identification of two
      more pairs of motifs, one of which included the CDE/CHR tandem element, as
      features associated with down-regulation both in the differentiating myoblasts
      and in the developing hippocampus. Of the features we identified, the E2F and
      CDE/CHR motifs may be associated with the cycling progenitor cell status, while
      NR2F may be related to the entry into differentiation along the neuronal pathway.
      CONCLUSION: Our results constitute the first prediction of an expression pattern
      from the genomic sequence for the developing mammalian brain, and demonstrate a
      potential for the analysis of gene regulation in a subspace of a single SVD mode
      of expression.

PMID- 16884530
TI  - Ventilator-associated pneumonia using a heated humidifier or a heat and moisture
      exchanger: a randomized controlled trial [ISRCTN88724583].
AB  - INTRODUCTION: Some guidelines to prevent ventilator-associated pneumonia (VAP) do
      not establish a recommendation for the preferential use of either heat and
      moisture exchangers (HMEs) or heated humidifiers (HHs), while other guidelines
      clearly advocate the use of HMEs. The aim of this study was to determine the
      incidence of VAP associated with HHs or HMEs. METHODS: A randomized study was
      conducted in the intensive care unit of a university hospital involving patients
      expected to require mechanical ventilation for >5 days. Patients were assigned to
      two groups; one group received HH and the other group received HME. Tracheal
      aspirate samples were obtained on endotracheal intubation, then twice a week, and
      finally on extubation, in order to diagnose VAP. Throat swabs were taken on
      admission to the intensive care unit, then twice a week, and finally at discharge
      from the intensive care unit in order to classify VAP as primary endogenous,
      secondary endogenous, or exogenous. RESULTS: A total of 120 patients were
      assigned to HMEs (60 patients) and HHs (60 patients); 16 patients received
      mechanical ventilation for less than five days and were excluded from the
      analysis. Data analysis of the remaining 104 patients (53 HMEs and 51 HHs) showed
      no significant differences between groups regarding sex, age, Acute Physiology
      and Chronic Health Evaluation II score, pre-VAP use of antibiotics, days on
      mechanical ventilation, and diagnosis group. VAP was found in eight of 51
      (15.69%) patients in the HH group and in 21 of 53 (39.62%) patients in the HME
      group (P = 0.006). The median time free of VAP was 20 days (95% confidence
      interval, 13.34-26.66) for the HH group and was 42 days (95% confidence interval,
      35.62-48.37) for the HME group (P <0.001). Cox regression analysis showed the HME
      as a risk factor for VAP (hazard rate, 16.2; 95% confidence interval, 4.54-58.04;
      P < 0.001). CONCLUSION: The patients mechanically ventilated during more than 5
      days developed a lower incidence of VAP with a heated humidifier than heat and
      moisture exchanger.

PMID- 16884531
TI  - Association of surfactant protein A polymorphisms with otitis media in infants at
      risk for asthma.
AB  - BACKGROUND: Otitis media is one of the most common infections of early childhood.
      Surfactant protein A functions as part of the innate immune response, which plays
      an important role in preventing infections early in life. This prospective study
      utilized a candidate gene approach to evaluate the association between
      polymorphisms in loci encoding SP-A and risk of otitis media during the first
      year of life among a cohort of infants at risk for developing asthma. METHODS:
      Between September 1996 and December 1998, women were invited to participate if
      they had at least one other child with physician-diagnosed asthma. Each mother
      was given a standardized questionnaire within 4 months of her infant's birth.
      Infant respiratory symptoms were collected during quarterly telephone interviews
      at 6, 9 and 12 months of age. Genotyping was done on 355 infants for whom whole
      blood and complete otitis media data were available. RESULTS: Polymorphisms at
      codons 19, 62, and 133 in SP-A1, and 223 in SP-A2 were associated with
      race/ethnicity. In logistic regression models incorporating estimates of
      uncertainty in haplotype assignment, the 6A4/1A5haplotype was protective for
      otitis media among white infants in our study population (OR 0.23; 95% CI
      0.07,0.73). CONCLUSION: These results indicate that polymorphisms within SP-A
      loci may be associated with otitis media in white infants. Larger confirmatory
      studies in all ethnic groups are warranted.

PMID- 16884532
TI  - Characterization of tamoxifen and 4-hydroxytamoxifen glucuronidation by human
      UGT1A4 variants.
AB  - INTRODUCTION: Tamoxifen (TAM) is an antiestrogen widely used in the treatment and
      prevention of breast cancer in women. One of the major mechanisms of metabolism
      of TAM and one of its major active metabolites, 4-hydroxytamoxifen (4-OH-TAM), is
      via glucuronidation. In the present study, the glucuronidating activities of
      three common variant isoforms encoded by the human UDP-glucuronosyltransferase
      (UGT) 1A4 gene were examined against TAM, trans-4-OH-TAM and cis-4-OH-TAM.
      METHODS: HPLC was used to detect glucuronide conjugates in microsomes from UGT1A4
      overexpressing HK293 cells. The UGT1A4 wild-type cDNA was synthesized by RT-PCR
      using normal human liver total RNA. The UGT1A424Thr/48Leu and UGT1A424Pro/48Val
      variants were generated by site-directed mutagenesis of the pcDNA3.1/V5-His-TOPO
      plasmid expressing wild-type UGT1A424Pro/48Leu. Levels of UGT1A4 expression in
      UGT-overexpressing cell lines were measured by western blot analysis. RESULTS:
      Microsomes from wild-type UGT1A424Pro/48Leu-overexpressing HK293 cells exhibited
      significant levels of activity against TAM, trans-4-OH-TAM and cis-4-OH-TAM,
      forming exclusively the tamoxifen quaternary ammonium glucuronide (TAM-N+
      glucuronide) and the 4-hydroxytamoxifen quaternary ammonium glucuronides (trans-4
      OH-TAM-N+-glucuronide and cis-4-OH-TAM-N+-glucuronide) with apparent Km values of
      2.0 microM, 2.2 microM, and 2.1 microM, respectively. Higher glucuronidation
      activities were found by kinetic analysis for microsomes from the variant
      UGT1A424Pro/48Val-overexpressing cell line as compared with microsomes from wild
      type UGT1A424Pro/48Leu-overexpressing cells against TAM and against both the
      trans and cis isomers of 4-OH-TAM. A significantly (P < 0.02) lower Km value
      (approximately 1.6-fold to 1.8-fold) was observed for both 4-OH-TAM isomers,
      while a near-significant (P = 0.053) decrease in Km was observed for TAM for the
      UGT1A424Pro/48Val variant as compared with wild-type UGT1A4. The Vmax/Km ratio
      for the UGT1A424Pro/48Val variant was significantly (P < or = 0.005) higher than
      that observed for the wild-type UGT1A4 isoform for both the trans and cis isomers
      of 4-OH-TAM after normalization for UGT1A4 expression by western blotting. No
      significant effect on enzyme kinetics was observed for the UGT1A424Thr/48Leu
      variant against either isomer of 4-OH-TAM or with TAM. CONCLUSION: These data
      suggest that the UGT1A4 codon 48 Leu>Val polymorphism significantly alters
      glucuronidation rates against TAM and its active hydroxylated metabolites, and
      that this polymorphism may play an important role in individual pharmacological
      response to TAM therapy.

PMID- 16884533
TI  - Growth, current size and the role of the 'reversal paradox' in the foetal origins
      of adult disease: an illustration using vector geometry.

PMID- 16884535
TI  - Funnel plots, performance variation and the Myocardial Infarction National Audit
      Project 2003-2004.
AB  - BACKGROUND: Clinical governance requires health care professionals to improve
      standards of care and has resulted in comparison of clinical performance data.
      The Myocardial Infarction National Audit Project (a UK cardiology dataset)
      tabulates its performance. However funnel plots are the display method of choice
      for institutional comparison. We aimed to demonstrate that funnel plots may be
      derived from MINAP data and allow more meaningful interpretation of data.
      METHODS: We examined the attainment of National Service Framework standards for
      all hospitals (n = 230) and all patients (n = 99,133) in the MINAP database
      between 1st April 2003 and 31st March 2004. We generated funnel plots (with
      control limits at 3 sigma) of Door to Needle and Call to Needle thrombolysis
      times, and the use of aspirin, beta-blockers and statins post myocardial
      infarction. RESULTS: Only 87,427 patients fulfilled criteria for analysis of the
      use of secondary prevention drugs and 15,111 patients for analysis by Door to
      Needle and Call to Needle times (163 hospitals achieved the standards for Door to
      Needle times and 215 were within or above their control limits). One hundred and
      sixteen hospitals fell outside the 'within 25%' and 'more than 25%' standards for
      Call to Needle times, but 28 were below the lower control limits. Sixteen
      hospitals failed to reach the standards for aspirin usage post AMI and 24
      remained below the lower control limits. Thirty hospitals were below the lower CL
      for beta-blocker usage and 49 outside the standard. Statin use was comparable.
      CONCLUSION: Funnel plots may be applied to a complex dataset and allow visual
      comparison of data derived from multiple health-care units. Variation is readily
      identified permitting units to appraise their practices so that effective quality
      improvement may take place.

PMID- 16884534
TI  - A novel role for 3, 4-dichloropropionanilide (DCPA) in the inhibition of prostate
      cancer cell migration, proliferation, and hypoxia-inducible factor 1alpha
      expression.
AB  - BACKGROUND: The amide class compound, 3, 4-dichloropropionanilide (DCPA) is known
      to affect multiple signaling pathways in lymphocyte and macrophage including the
      inhibition of NF-kappaB ability. However, little is known about the effect of
      DCPA in cancer cells. Hypoxia-inducible factor 1 (HIF-1) regulates the expression
      of many genes including vascular endothelial growth factor (VEGF), heme oxygenase
      1, inducible nitric oxide synthase, aldolase, enolase, and lactate dehydrogenase
      A. HIF-1 expression is associated with tumorigenesis and angiogenesis. METHODS:
      We used Transwell assay to study cell migration, and used immunoblotting to study
      specific protein expression in the cells. RESULTS: In this report, we demonstrate
      that DCPA inhibited the migration and proliferation of DU145 and PC-3 prostate
      cancer cells induced by serum, insulin, and insulin-like growth factor I (IGF-I).
      We found that DCPA inhibited HIF-1 expression in a subunit-specific manner in
      these cancer cell lines induced by serum and growth factors, and decreased HIF
      1alpha expression by affecting its protein stability. CONCLUSION: DCPA can
      inhibit prostate cancer cell migration, proliferation, and HIF-1alpha expression,
      suggesting that DCPA could be potentially used for therapeutic purpose for
      prostate cancer in the future.

PMID- 16884536
TI  - Explaining variation in GP referral rates for x-rays for back pain.
AB  - BACKGROUND: Despite the availability of clinical guidelines for the management of
      low back pain (LBP), there continues to be wide variation in general
      practitioners' (GPs') referral rates for lumbar spine x-ray (LSX). This study
      aims to explain variation in GPs' referral rates for LSX from their accounts of
      the management of patients with low back pain. METHODS: Qualitative, semi
      structured interviews with 29 GPs with high and low referral rates for LSX in
      North East England. Thematic analysis used constant comparative techniques.
      RESULTS: Common and divergent themes were identified among high- and low-users of
      LSX. Themes that were similar in both groups included an awareness of current
      guidelines for the use of LSX for patients with LBP and the pressure from
      patients and institutional factors to order a LSX. Differentiating themes for the
      high-user group included: a belief that LSX provides reassurance to patients that
      can outweigh risks, pessimism about the management options for LBP, and a belief
      that denying LSX would adversely affect doctor-patient relationships. Two
      specific differentiating themes are considered in more depth: GPs' awareness of
      their use of lumbar spine radiology relative to others, and the perceived risks
      associated with LSX radiation. CONCLUSION: Several key factors differentiate the
      accounts of GPs who have high and low rates of referral for LSX, even though they
      are aware of clinical guideline recommendations. Intervention studies that aim to
      increase adherence to guideline recommendations on the use of LSX by changing the
      ordering behaviour of practitioners in primary care should focus on these
      factors.

PMID- 16884537
TI  - Novel missense mutations of the Deleted-in-AZoospermia-Like (DAZL) gene in
      infertile women and men.
AB  - BACKGROUND: The Deleted-in-AZoospermia-Like (DAZL) gene has homologs required for
      germ cell development in many organisms. Recently, we showed that there are
      several common polymorphisms within the DAZL gene that are associated with age at
      ovarian failure/menopause and sperm count. METHODS: Here we sought to identify
      rare mutations in DAZL and examine their phenotypes in men and women. We
      sequenced the DAZL gene in 519 individuals; sequences spanned the entire coding
      region of the gene. RESULTS: We report the identification of four putative
      missense mutations in DAZL. Three individuals that were heterozygous for a DAZL
      mutation reported having children, while two individuals that were homozygous
      reported no children. These mutations were found only in infertile men and women.
      CONCLUSION: Given the strong data associating DAZL polymorphisms and deletions
      with fertility in humans and model organisms, we suggest that these mutations may
      be associated with age at menopause and/or sperm count and warrant further
      biochemical and genetic investigation.

PMID- 16884538
TI  - Comparative genomics of the class 4 histone deacetylase family indicates a
      complex evolutionary history.
AB  - BACKGROUND: Histone deacetylases are enzymes that modify core histones and play
      key roles in transcriptional regulation, chromatin assembly, DNA repair, and
      recombination in eukaryotes. Three types of related histone deacetylases (classes
      1, 2, and 4) are widely found in eukaryotes, and structurally related proteins
      have also been found in some prokaryotes. Here we focus on the evolutionary
      history of the class 4 histone deacetylase family. RESULTS: Through sequence
      similarity searches against sequenced genomes and expressed sequence tag data, we
      identified members of the class 4 histone deacetylase family in 45 eukaryotic and
      37 eubacterial species representative of very distant evolutionary lineages.
      Multiple phylogenetic analyses indicate that the phylogeny of these proteins is,
      in many respects, at odds with the phylogeny of the species in which they are
      found. In addition, the eukaryotic members of the class 4 histone deacetylase
      family clearly display an anomalous phyletic distribution. CONCLUSION: The
      unexpected phylogenetic relationships within the class 4 histone deacetylase
      family and the anomalous phyletic distribution of these proteins within
      eukaryotes might be explained by two mechanisms: ancient gene duplication
      followed by differential gene losses and/or horizontal gene transfer. We discuss
      both possibilities in this report, and suggest that the evolutionary history of
      the class 4 histone deacetylase family may have been shaped by horizontal gene
      transfers.

PMID- 16884539
TI  - Quality of life in patients with various Barrett's esophagus associated health
      states.
AB  - BACKGROUND: The management of Barrett's esophagus (BE), particularly high grade
      dysplasia (HGD), is an area of much debate and controversy. Surgical
      esophagectomy, intensive endoscopic surveillance and mucosal ablative techniques,
      especially photodynamic therapy (PDT), have been proposed as possible management
      strategies. The purpose of this study was to determine the health related quality
      of life associated with Barrett's esophagus and many of the pivotal health states
      associated with Barrett's HGD management. METHODS: 20 patients with Barrett's
      esophagus were enrolled in a pilot survey study at a large urban hospital. The
      utility of Barrett's esophagus without dysplasia (current health state) as well
      as various health states associated with HGD management (hypothetical states as
      the subject did not have HGD) were measured using a validated health utility
      instrument (Paper Standard Gamble). These specific health states were chosen for
      the study because they are considered pivotal in Barrett's HGD decision making.
      Information regarding Barrett's HGD was presented to the subject in a
      standardized format that was designed to be easily comprehendible. RESULTS: The
      average utility scores (0-1 with 0 = death and 1 = perfect health) for the
      various Barrett's esophagus associated states were: BE without dysplasia-0.95;
      Post-esophagectomy for HGD with dysphagia-0.92; Post-PDT for HGD with recurrence
      uncertainty-0.93; Post-PDT for HGD with recurrence uncertainty and dysphagia
      0.91; Intensive endoscopic surveillance for HGD-0.90. CONCLUSION: We present the
      scores for utilities associated with Barrett's esophagus as well as various
      states associated with the management of HGD. The results of our study may be
      useful in advising patients and providers regarding expected outcomes of the
      various HGD management strategies as well as providing utility scores for future
      cost-effectiveness analyses.

PMID- 16884541
TI  - Body mass index, sexual behaviour, and sexually transmitted infections: an
      analysis using the NHANES 1999-2000 data.
AB  - BACKGROUND: Factors determining human sexual behaviour are not completely
      understood, but are important in the context of sexually transmitted disease
      epidemiology and prevention. Being obese is commonly associated with a reduced
      physical attractiveness but the associations between body mass index, sexual
      behaviour and the risk of acquiring sexually transmitted infections has never
      been studied. METHODS: The National Health and Nutrition Examination Survey
      (NHANES) files of 1999-2000 were used. Linear regression was used to relate the
      reported number of sex partners in the last year and lifetime to Body Mass Index
      (BMI). Logistic regression was used to relate Herpes Simplex Virus type II (HSV
      2) antibodies to BMI and other variables. RESULTS: Data on 979 men and 1250 women
      were available for analysis. Obese (mean number of partners for men:1.12, women:
      0.93) and overweight (mean for men: 1.38, women: 1.03) individuals reported fewer
      partners than individuals of normal BMI (mean for men: 2.00, women: 1.15) in the
      last year (p < .0.01 & p < 0.05 for men, p < 0.05 & n.s. for women). The same
      relationship held for lifetime partners in men (mean 11.94, 18.80, and 22.08 for
      obese, overweight and normal BMI respectively (p < 0.05 & n.s. for obese and
      overweight vs normal respectively), but not in women (mean 7.96, 4.77, and 5.24
      respectively). HSV-2 antibodies were significantly correlated with the number of
      lifetime partners in both men and women, with the odds of being HSV-2 positive
      increasing by 0.6% (p < 0.01) and 2.7% (p < 0.01) for men and women respectively.
      HSV-2 antibodies increased with age, even after adjustment for lifetime partners
      (p < 0.01). Being obese (HSV-2 prevalence 15.9 and 34.9% for men and women
      respectively) or overweight (HSV-2 prevalence 16.7 and 29.3 for men and women
      respectively) was not associated with HSV-2 antibodies (HSV-2 prevalence for
      normal BMI: 15.6 and 23.2% respectively), independent of whether the association
      was adjusted for life time sexual partners or not. There was evidence of
      substantial misreporting of sexual behaviour. CONCLUSION: Obese and overweight
      individuals, especially men, self report fewer sex partners than individuals of
      normal weight, but surprisingly this is not reflected in their risk of HSV-2
      infection. HSV-2 antibodies provide information not contained in self-reported
      number of partners and may better estimate sexual risk than self-reported
      behaviour.

PMID- 16884540
TI  - Laminin-332 alters connexin profile, dye coupling and intercellular Ca2+ waves in
      ciliated tracheal epithelial cells.
AB  - BACKGROUND: Tracheal epithelial cells are anchored to a dynamic basement membrane
      that contains a variety of extracellular matrix proteins including collagens and
      laminins. During development, wound repair and disease of the airway epithelium,
      significant changes in extracellular matrix proteins may directly affect cell
      migration, differentiation and events mediated by intercellular communication. We
      hypothesized that alterations in cell matrix, specifically type I collagen and
      laminin alpha3beta3gamma2 (LM-332) proteins within the matrix, directly affect
      intercellular communication in ciliated rabbit tracheal epithelial cells (RTEC).
      METHODS: Functional coupling of RTEC was monitored by microinjection of the
      negatively charged fluorescent dyes, Lucifer Yellow and Alexa 350, into ciliated
      RTEC grown on either a LM-332/collagen or collagen matrix. Coupling of
      physiologically significant molecules was evaluated by the mechanism and extent
      of propagated intercellular Ca2+ waves. Expression of connexin (Cx) mRNA and
      proteins were assayed by reverse transcriptase - polymerase chain reaction and
      immunocytochemistry, respectively. RESULTS: When compared to RTEC grown on
      collagen alone, RTEC grown on LM-332/collagen displayed a significant increase in
      dye transfer. Although mechanical stimulation of RTEC grown on either LM
      332/collagen or collagen alone resulted in intercellular Ca2+ waves, the
      mechanism of transfer was dependent on matrix: RTEC grown on LM-332/collagen
      propagated Ca2+waves via extracellular purinergic signaling whereas RTEC grown on
      collagen used gap junctions. Comparison of RTEC grown on collagen or LM
      332/collagen matrices revealed a reorganization of Cx26, Cx43 and Cx46 proteins.
      CONCLUSION: Alterations in airway basement membrane proteins such as LM-332 can
      induce connexin reorganizations and result in altered cellular communication
      mechanisms that could contribute to airway tissue function.

PMID- 16884542
TI  - Normative and self-perceived orthodontic treatment need of a Peruvian university
      population.
AB  - BACKGROUND: Previous studies on orthodontic treatment need in young adults have
      shown that up to 50% had malocclusions that needed orthodontic treatment. The
      aims of this study were to assess the normative and self-perceived need for
      orthodontic treatment using the Index of Orthodontic Treatment Need (IOTN) and to
      determine if the treatment need levels were influenced by sex, age and socio
      economic status (SES) in a sample of Peruvian young adults. METHODS: 281 first
      year students (157 male and 124 female students) with a mean age of 18.1 +/- 1.6
      years were randomly selected and evaluated through the Dental Health Component
      (DHC) and Aesthetic Component (AC) of the IOTN. Structured interview and clinical
      examination were used to assess the students. Descriptive statistics and Chi
      square tests were used for data analysis with statistical significance set at P <
      0.05. RESULTS: An intra-examiner reliability of 0.89 was obtained (weighted
      Kappa). The percentage of students according to SES was 51.2%, 40.6% and 8.2%
      corresponding to low, medium and high SES respectively. The percentage of
      students with DHC grades 4-5 was 29.9% whereas the percentage of students with AC
      grades 8-10 was 1.8%. There were no significant differences in the distribution
      of normative and self-perceived orthodontic treatment need based on sex, age and
      SES comparisons. CONCLUSION: Normative orthodontic treatment need was not matched
      by a similar level of self-perceived treatment need in these young adults. Sex,
      age and SES were non-significant factors associated with levels of treatment
      need.

PMID- 16884543
TI  - Japanese version of the Dermatology Life Quality Index: validity and reliability
      in patients with acne.
AB  - BACKGROUND: Patient-reported quality of life is strongly affected by some
      dermatologic conditions. We developed a Japanese version of the Dermatology Life
      Quality Index (DLQI-J) and used psychometric methods to examine its validity and
      reliability. METHODS: The Japanese version of the DLQI was created from the
      original (English) version, using a standard method. The DLQI-J was then
      completed by 197 people, to examine its validity and reliability. Some
      participants completed the DLQI-J a second time, 3 days later, to examine the
      reproducibility of their responses. In addition to the DLQI-J, the participants
      completed parts of the SF-36 and gave data on their demographic and clinical
      characteristics. Their physicians provided information on the location and
      clinical severity of the skin disease. RESULTS: The participants reported no
      difficulties in answering the DLQI-J items. Their mean age was 24.8 years, 77.2%
      were female, and 78.7% had acne vulgaris. The mean score of DLQI was 3.99(SD:
      3.99). The responses were found to be reproducible and stable. Results of
      principal-component and factor analysis suggested that this scale measured one
      construct. The correlations of DLQI-J scores with sex or age were very poor, but
      those with SF-36 scores and with clinical severity were high. CONCLUSION: The
      DLQI-J provides valid and reliable data despite having only a small number of
      items.

PMID- 16884544
TI  - Identification and analysis of YELLOW protein family genes in the silkworm,
      Bombyx mori.
AB  - BACKGROUND: The major royal jelly proteins/yellow (MRJP/YELLOW) family possesses
      several physiological and chemical functions in the development of Apis mellifera
      and Drosophila melanogaster. Each protein of the family has a conserved domain
      named MRJP. However, there is no report of MRJP/YELLOW family proteins in the
      Lepidoptera. RESULTS: Using the YELLOW protein sequence in Drosophila
      melanogaster to BLAST silkworm EST database, we found a gene family composed of
      seven members with a conserved MRJP domain each and named it YELLOW protein
      family of Bombyx mori. We completed the cDNA sequences with RACE method. The
      protein of each member possesses a MRJP domain and a putative cleavable signal
      peptide consisting of a hydrophobic sequence. In view of genetic evolution, the
      whole Bm YELLOW protein family composes a monophyletic group, which is distinctly
      separate from Drosophila melanogaster and Apis mellifera. We then showed the
      tissue expression profiles of Bm YELLOW protein family genes by RT-PCR.
      CONCLUSION: A Bombyx mori YELLOW protein family is found to be composed of at
      least seven members. The low homogeneity and unique pattern of gene expression by
      each member among the family ensure us to prophesy that the members of Bm YELLOW
      protein family would play some important physiological functions in silkworm
      development.

PMID- 16884545
TI  - The neurochemical basis of human cortical auditory processing: combining proton
      magnetic resonance spectroscopy and magnetoencephalography.
AB  - BACKGROUND: A combination of magnetoencephalography and proton magnetic resonance
      spectroscopy was used to correlate the electrophysiology of rapid auditory
      processing and the neurochemistry of the auditory cortex in 15 healthy adults. To
      assess rapid auditory processing in the left auditory cortex, the amplitude and
      decrement of the N1m peak, the major component of the late auditory evoked
      response, were measured during rapidly successive presentation of acoustic
      stimuli. We tested the hypothesis that: (i) the amplitude of the N1m response and
      (ii) its decrement during rapid stimulation are associated with the cortical
      neurochemistry as determined by proton magnetic resonance spectroscopy. RESULTS:
      Our results demonstrated a significant association between the concentrations of
      N-acetylaspartate, a marker of neuronal integrity, and the amplitudes of
      individual N1m responses. In addition, the concentrations of choline-containing
      compounds, representing the functional integrity of membranes, were significantly
      associated with N1m amplitudes. No significant association was found between the
      concentrations of the glutamate/glutamine pool and the amplitudes of the first
      N1m. No significant associations were seen between the decrement of the N1m (the
      relative amplitude of the second N1m peak) and the concentrations of N
      acetylaspartate, choline-containing compounds, or the glutamate/glutamine pool.
      However, there was a trend for higher glutamate/glutamine concentrations in
      individuals with higher relative N1m amplitude. CONCLUSION: These results suggest
      that neuronal and membrane functions are important for rapid auditory processing.
      This investigation provides a first link between the electrophysiology, as
      recorded by magnetoencephalography, and the neurochemistry, as assessed by proton
      magnetic resonance spectroscopy, of the auditory cortex.

PMID- 16884546
TI  - Identification and quantification of change in Australian illicit drug markets.
AB  - BACKGROUND: In early 2001 Australia experienced a sudden reduction in the
      availability of heroin which had widespread effects on illicit drug markets
      across the country. The consequences of this event, commonly referred to as the
      Australian 'heroin shortage', have been extensively studied and there has been
      considerable debate as to the causes of the shortage and its implications for
      drug policy. This paper aims to investigate the presence of these epidemic
      patterns, to quantify the scale over which they occur and to estimate the
      relative importance of the 'heroin shortage' and any epidemic patterns in the
      drug markets. METHOD: Key indicator data series from the New South Wales illicit
      drug market were analysed using the statistical methods Principal Component
      Analysis and SiZer. RESULTS: The 'heroin shortage' represents the single most
      important source of variation in this illicit drug market. Furthermore the size
      of the effect of the heroin shortage is more than three times that evidenced by
      long-term 'epidemic' patterns. CONCLUSION: The 'heroin shortage' was unlikely to
      have been a simple correction at the end of a long period of reduced heroin
      availability, and represents a separate non-random shock which strongly affected
      the markets.

PMID- 16884548
TI  - Brain olfactory activation measured by near-infrared spectroscopy in humans.
AB  - In recent years, near-infrared spectroscopy (NIRS) has been used to study
      functional activation of various areas of the brain. This is based on the
      assumption that an increase in the recorded oxygenated haemoglobin (HbO2)
      concentration represents an increase in blood flow, which in turn reflects
      neuronal activation. The aim of this preliminary study was to use NIRS to monitor
      the activity of the olfactory cortex, as mirrored by the haemodynamic response,
      when subjects were exposed to olfactory stimuli. A NIRO 300 (Hamamatsu Photonics,
      Hamamatsu, Japan) device was used. The optodes were placed on the right forehead
      and right temporal, parietal and occipital regions. Changes in the concentration
      of HbO2 and deoxygenated haemoglobin during olfactory stimulation were monitored.
      Olfactory stimulation was performed with vanilla essence, strawberry essence and
      scatol. During olfactory stimulation, cerebral HbO2 concentration increased over
      the frontal region. However, in the temporal, parietal and occipital regions,
      little or no HbO2 changes were recorded. This study shows that human brain
      cortical activation following olfactory stimulation can be recorded by NIRS. This
      NIRS analysis may therefore provide the basis for future development of an
      objective olfactory test in humans.

PMID- 16884547
TI  - C. elegans feeding defective mutants have shorter body lengths and increased
      autophagy.
AB  - BACKGROUND: Mutations that cause feeding defects in the nematode C. elegans are
      known to increase life span. Here we show that feeding defective mutants also
      have a second general trait in common, namely that they are small. RESULTS: Our
      measurements of the body lengths of a variety of feeding defective mutants, or of
      a variety of double mutants affecting other pathways that regulate body length in
      C. elegans, i.e. the DBL-1/TGFbeta, TAX-6/calcineurin and the SMA-1/betaH
      spectrin pathways, indicate that food uptake acts as a separate pathway
      regulating body length. In early stages, before eating begins, feeding defective
      worms have no defect in body length or, in some cases, have only slightly smaller
      body length compared to wild-type. A significant difference in body length is
      first noticeable at later larval stages, a difference that probably correlates
      with increasing starvation. We also show that autophagy is induced and that the
      quantity of fat is decreased in starved worms. CONCLUSION: Our results indicate
      that the long-term starvation seen in feeding-defective C. elegans mutants
      activates autophagy, and leads to depletion of fat deposits, small cell size and
      small body size.

PMID- 16884549
TI  - Management of retrosternal goitres: results of early surgical intervention to
      prevent airway morbidity, and a review of the English literature.
AB  - We present our experience and also review the world literature on the management
      of retrosternal goitres (RSGs). There is now irrefutable evidence that almost all
      RSGs will continue to grow and eventually cause airway compression. We describe
      the diagnosis, investigation and surgical approach to the management of this
      condition.

PMID- 16884550
TI  - Influence of diabetes mellitus on deep neck infection.
AB  - OBJECTIVE: To investigate the influence of hyperglycaemia on deep neck infection
      (DNI) and the differences between the diabetic and non-diabetic form of DNI.
      STUDY DESIGN AND SETTING: Retrospective review of 131 patients with DNI treated
      between 1993 and 2002 at Shin Kong Memorial Hospital, Taipei, Taiwan. RESULTS:
      Deep neck infection was significantly more prevalent in patients with diabetes
      mellitus (DM) over 60 years of age than in non-DM subjects of a similar age (p =
      0.004). In the DM group, Klebsiella pneumoniae was the most common aerobic
      pathogen and tended to involve more than two anatomical spaces (p < 0.0001).
      Seventeen out of 18 patients (94.4 per cent) displayed an elevated (> or = 7 per
      cent) glycosylated haemoglobin level. The DM group had a significantly higher
      complication rate, longer hospital stay and tracheotomy rate than the non-DM
      group. CONCLUSIONS: Diabetic DNI differs from non-diabetic DNI in several aspects
      and is associated with a higher morbidity. A greater than normal haemoglobin A1c
      level was commonly observed.

PMID- 16884551
TI  - Methylene blue toxicity following infusion to localize parathyroid adenoma.

PMID- 16884552
TI  - The effect of lidocaine and sufentanil in preventing intraocular pressure
      increase due to succinylcholine and endotracheal intubation.
AB  - BACKGROUND AND OBJECTIVE: Succinylcholine administration, laryngoscopy and
      tracheal intubation are followed by increased intraocular pressure. Various
      premedications have been advocated for preventing increases in intraocular
      pressure, especially in patients undergoing surgical repair of open globe due to
      penetrating eye trauma. Results of studies in this area have been controversial.
      METHODS: In this double-blind study, three groups of 70 patients receiving
      sufentanil, lidocaine and placebo 90 s prior to intubation were evaluated and
      compared for intraocular pressure changes following succinylcholine
      administration, laryngoscopy and tracheal intubation. RESULTS: Mean intraocular
      pressure measured 2 and 3 min after succinylcholine administration in groups
      receiving sufentanil and lidocaine was significantly lower than in the placebo
      group. Mean intraocular pressure changes in the three groups were -1.84, -2.03
      and +2.82 mmHg, respectively in minute 2; -4.78, -4.73 and +1.35 mmHg,
      respectively in minute 5. There was a significant intraocular pressure decrease
      in the sufentanil and lidocaine groups, compared to the placebo group. The eye
      surgeons' satisfaction was also significantly higher with the sufentanil and
      lidocaine groups. CONCLUSION: Previous studies have yielded controversial results
      as to the effect of sufentanil and lidocaine in preventing intraocular pressure
      following succinylcholine administration, laryngoscopy and tracheal intubation.
      The present study affirms the preventive effect of these drugs on intraocular
      pressure increase.

PMID- 16884553
TI  - Propofol-remifentanil-based anaesthesia vs. sevoflurane-fentanyl-based
      anaesthesia for immediate postoperative ophthalmic evaluation following
      strabismus surgery.
AB  - BACKGROUND AND OBJECTIVE: Following strabismus surgery, immediate postoperative
      ophthalmic evaluation may be desired. Thus, an anaesthetic technique allowing
      rapid recovery of ocular motility is required. Saccadic eye movements is a
      biophysical monitor of ocular motility and may be used to assess recovery from
      anaesthesia. The aim of this study is to compare the time to the recovery of
      saccadic eye movements in patients, following one of two anaesthetic techniques:
      Propofol-remifentanil-based anaesthesia vs. sevoflurane-fentanyl-based
      anaesthesia. METHODS: Fifty adult patients undergoing strabismus surgery were
      randomly assigned to one of two groups: patients in Group R received induction
      and maintenance of anaesthesia with propofol and remifentanil, while patients in
      Group S received induction of anaesthesia with propofol and fentanyl and
      maintenance of anaesthesia with sevoflurane. Recovery from anaesthesia was
      measured from the time all anaesthetics were turned off and was assessed every 2
      min. Recovery time was attained when patients were able to generate brisk
      saccadic eye movements. At recovery time, the ophthalmic evaluation was started.
      RESULTS: The mean recovery time of saccadic eye movements was significantly
      shorter in the Group R when compared to the Group S (12.1 +/- 4.3 min vs. 21.5 +/
      4.7 min, respectively, P < 0.0001). More patients in Group S experienced nausea
      and vomiting postoperatively as compared to Group R (9/25 vs. 2/25, respectively,
      P = 0.037). CONCLUSIONS: Propofol-remifentanil-based anaesthesia may be a useful
      technique in strabismus surgery when immediate postoperative ophthalmic
      evaluation is desired. When compared to sevoflurane maintenance of anaesthesia,
      it allows for a more rapid recovery from anaesthesia as judged by recovery of
      saccadic eye movements and a decreased incidence of postoperative nausea and
      vomiting.

PMID- 16884554
TI  - Unchanged rat brain amyloid precursor protein levels after exposure to
      benzodiazepines in vivo.
AB  - BACKGROUND AND OBJECTIVE: Recent studies emphasize a positive correlation between
      (cardiac) surgical interventions and increased risk for developing Alzheimer's
      disease in the late postoperative period. Since amyloid precursor protein and its
      neurotoxic derivatives play key roles in the development of Alzheimer's dementia,
      the impact of several agents used in the intra- and perioperative period is
      examined. METHOD: Amyloid precursor protein concentrations were assessed by semi
      quantitative Western-immunoblot in brains of rats following intraperitoneal
      treatment with diazepam and midazolam. RESULTS: There were no significant changes
      in the amyloid precursor protein concentrations. CONCLUSION: Both diazepam and
      midazolam are considered to be relatively safe with respect to amyloid precursor
      protein metabolism.

PMID- 16884555
TI  - Early heparin-induced thrombocytopaenia (HIT) after cardiac surgery.

PMID- 16884556
TI  - Legionella pneumonia with acute respiratory distress syndrome, myocarditis and
      septic shock successfully treated with Drotrecogin Alpha (activated).

PMID- 16884557
TI  - Spontaneous gastric perforation.

PMID- 16884558
TI  - Electroconvulsive therapy for catatonia resulting in cardiac arrest.

PMID- 16884559
TI  - Intracellular mechanism of the negative inotropic effect induced by alpha1
      adrenoceptor stimulation in mouse myocardium.
AB  - Alpha(1)-adrenoceptor stimulation (alpha(1)ARS) shows a positive inotropic effect
      in most mammalian myocardium. In mouse myocardium, however, alpha(1)ARS showed
      the negative inotropic effect, of which intracellular mechanisms are not fully
      clarified. The purpose of this study is to investigate the intracellular
      mechanism of the negative inotropic effect by alpha(1)ARS in C57BL/6 mouse
      myocardium. We used isolated ventricular papillary muscles of C57BL/6 strain
      mouse which is widely used for genetic manipulation. We simultaneously measured
      isometric tension and intracellular Ca(2+) concentration ([Ca(2+)](i)) using the
      aequorin method. In twitch contraction, phenylephrine concentration-dependently
      (1-100 microM) decreased tension without significant changes in the Ca(2+)
      transient, and these effects were completely blocked by prazosin (3 microM) or
      calphostin C (a PKC inhibitor, 1 microM). Phorbol 12-myristate 13-acetate (PMA)
      (a PKC activator, 1 microM) decreased tension as observed in phenylephrine. After
      PMA application, the negative inotropic effect of phenylephrine disappeared. To
      estimate the Ca(2+) sensitivity, tetanic contraction was produced, and the
      relation between [Ca(2+)](i) and tension at a steady state was measured.
      Phenylephrine (10 microM) decreased the Ca(2+) sensitivity, and PMA showed a
      similar Ca(2+) desensitizing effect. These results suggest that the negative
      inotropic effect of phenylephrine in mouse myocardium can be explained by the
      decrease in the Ca(2+) sensitivity through the activation of PKC. The present
      result indicates that the effect of alpha(1)ARS differs among species and strains
      of experiment animals. Thus, we should be careful about using the results of
      mouse myocardium to understand the functions of the human heart.

PMID- 16884560
TI  - Organizational decentralization in radiology.
AB  - At present, most hospitals have a department of radiology where images are
      captured and interpreted. Decentralization is the opposite of centralization and
      means 'away from the centre'. With a Picture Archiving and Communication System
      (PACS) and broadband communications, transmitting radiology images between sites
      will be far easier than before. Qualitative interviews of 26 resource persons
      were performed in Norway. There was a response rate of 90%. Decentralization of
      radiology interpretations seems less relevant than centralization, but several
      forms of decentralization have a role to play. The respondents mentioned several
      advantages, including exploitation of capacity and competence. They also
      mentioned several disadvantages, including splitting professional communities and
      reduced contact between radiologists and clinicians. With the new technology
      decentralization and centralization of image interpretation are important
      possibilities in organizational change. This will be important for the future of
      teleradiology.

PMID- 16884561
TI  - Enhanced pharmacy training for counter-terrorism and disaster response.
AB  - State and federal authorities in the USA have identified pharmacists as important
      in terrorism detection activities. However few pharmacists are trained for
      disaster response planning, or providing services at disaster sites. A distance
      training programme was created by the College of Pharmacy at the University of
      Kentucky, Chandler Medical Center (UKCMC) in collaboration with an academic
      Medical Center, urban and rural community pharmacists, experts in pharmacy and
      infectious disease, and two state pharmacy associations. There was a substantial
      improvement in bioterrorism training knowledge as judged by pre- and post-test
      results. During two years of training, a total of 142 licensed pharmacists
      received certification (approximately 4.7% of all those in Kentucky). In
      addition, a network of bioterrorism-trained pharmacists was created for the
      state.

PMID- 16884562
TI  - Accident and emergency teleconsultation for primary care--a systematic review of
      technical feasibility, clinical effectiveness, cost effectiveness and level of
      local management.
AB  - A systematic review of accident and emergency teleconsultation services was
      carried out. Studies (English language only) conducted worldwide and published
      between 1996 and 2003 were included. Evidence relating to technical feasibility,
      clinical effectiveness, cost effectiveness and level of local management was used
      as the main outcome measure. Thirty-one studies met the selection criteria. Only
      two studies were randomized controlled studies. All studies provided evidence
      that that the service was technically feasible. Of the studies, 97% suggested
      that the service was clinically effective; 48% (15) of the studies gave figures
      for the level of local management achieved. The range for local management was 35
      100% with a mean of 76%. Only 23% of the studies provided evidence to suggest
      that the service was cost effective. The case for cost-effectiveness is far from
      proven and this area of research requires immediate attention if potential users
      are to be convinced of the value of telemedicine.

PMID- 16884563
TI  - Telemedicine for diabetes support in family doctors' practices: a pilot project.
AB  - A telemedicine support system for diabetes management was compared with standard
      monitoring of patients with diabetes. The telemedicine system was composed of two
      modules: a Patient Unit and a Medical Unit connected by the telecommunication
      network. The study involved 60 patients of family doctors' practices in the Lower
      Silesia Region who were diagnosed with diabetes. There was no significant
      difference in haemoglobin A(1c) between telemonitoring and the traditional group
      of diabetic patients during the survey. The patients' quality of life slightly
      improved in the telemonitoring (mean score 3.4) and the traditionally monitored
      group (mean score 3.2), but there was no significant difference between them.
      Most of the telemonitoring patients (75%) expressed the desire to continue with
      telemedicine support and nearly 60% of patients monitored with traditional
      methods wanted to be included in the telemedicine group. The system seems to be
      reliable, simple to use and friendly for the patients.

PMID- 16884564
TI  - Public perception of realtime information services for environmental monitoring
      and management of asthma.
AB  - A questionnaire was distributed to asthma patients and relatives of paediatric
      patients in the Royal Brompton Hospital outpatient clinic in London during March
      2003. The aim was to determine how well informed those affected by asthma and
      allergic diseases were, to find out the best medium for distributing relevant
      information (e.g. Internet, mobile phones) and to discover the type of
      information they wished to receive. A total of 298 questionnaires were
      distributed and all were completed (100% response rate). The level of education
      of the respondents was high and the majority lived outside the London area. The
      questionnaire showed that the respondents would like to be informed about a wide
      range of information related to monitoring and self-management of asthma.
      Avoidance measurements and prevention was the first choice, followed closely by
      information on substances, and the environment and allergies. The Internet was
      the preferred means of communication with an information service provider. The
      telephone was also popular, and more popular than the mobile phone. The majority
      of participants were not willing to pay for an information service.

PMID- 16884565
TI  - Managing diabetes care using an integrated regional e-health approach.
AB  - A total of 175 patients with Types 1 and 2 diabetes in primary care and
      university hospital outpatient departments were randomized into a study group (n
      = 101) or usual care (n = 74). The study group used an e-health application with
      a diabetes management system and a home care link. Usual care did not involve e
      health, i.e. the patients made regular general practitioner visits about every
      three months. After 12 months HbA1c decreased significantly in both groups of
      patients. The differences were small, but HbA1c was significantly lower in the
      study group than the controls. Diastolic blood pressure, fasting plasma glucose,
      serum total cholesterol, serum LDL-cholesterol and serum triglycerides were
      significantly lower in the study than in the control group. This was achieved
      with fewer visits by study patients to doctors and nurses. Use of e-health in
      diabetes care for 12 months was able to provide equivalent diabetic control to
      usual care, and improved cardiovascular risk factors.

PMID- 16884566
TI  - Feasibility and acceptance of telemedicine for wound care in patients with
      chronic leg ulcers.
AB  - We examined the feasibility and acceptance of teledermatology for wound
      management of patients with chronic leg ulcers by home-care nurses. Forty-one
      chronic leg ulcers of different origin in 14 patients were included. After an
      initial in-person visit in which leg ulcers were assessed and classified, and
      underlying diseases noted, follow-up visits were done by home-care nurses. Once a
      week 1-4 digital images of the wound and surrounding skin and relevant clinical
      information were transmitted via a secure Website to an expert at the wound care
      centre. The experts provided an assessment of wound status and therapeutic
      recommendations. In 89% of the 492 teleconsultations, the quality of images was
      sufficient or excellent and the experts were confident giving therapeutic
      recommendations. Treatment modalities were changed or adapted in one-third of the
      consultations. There was a significant decrease in visits to a general physician
      or the wound care centre. The acceptance of teledermatology was high in patients,
      home-care nurses and wound experts. Teledermatology offers great potential for
      chronic wound care and seems to be accepted both by patients and health-care
      persons.

PMID- 16884567
TI  - Health and lifestyle management via interactive TV in patients with severe
      chronic cardiovascular diseases.
AB  - A pilot trial of an interactive TV system took place at the Royal Brompton
      Hospital, involving nine hospitalized and 12 non-hospitalized patients with adult
      congenital heart disease. Following a short training session, patients took their
      measurements (blood pressure, ECG measurement, oxygen saturation, bodyweight) and
      submitted their data through the interactive TV system. The majority perceived
      the system as useful, efficient and appropriate for use with their condition
      (67%), and they were satisfied with the usability of the system (71%). They
      considered that the information provided by the system was easy to understand and
      they liked using the system (62%). Overall, most patients (20) were satisfied
      with the system. The majority of the participants did not feel that the system
      affected their relationship with their doctor.

PMID- 16884568
TI  - A prospective case control study of the benefits of electronic discharge
      summaries.
AB  - A system of electronic discharge summaries was developed. It replaced
      conventional discharge prescriptions and dictated discharge summaries. We
      conducted a prospective case-control study of 102 consecutive patients admitted
      to our hospital under the care of one consultant physician. Patients discharged
      after 1 December 2004 were discharged using the new computerised system (50
      patients) while patients admitted under the same medical team, but to another
      ward were discharged using the conventional paper discharge system (52 patients).
      Patients in the electronic group and the conventional group were similar in age
      (mean 67 years versus 58 years, P>0.05) and duration of hospital stay (6 days
      versus 1 day, P>0.05). The mean time taken to produce an electronic discharge
      summary was immediate (0 days) which was significantly (P<0.0001) less than the
      mean time taken to produce a conventional discharge summary (80 days). Combining
      electronic discharge prescriptions with electronic summaries appears promising
      and merits further study.

PMID- 16884569
TI  - A qualitative study of the educational potential of joint teleconsultations at
      the primary-secondary care interface.
AB  - We conducted an evaluation of joint teleconsultations involving specialists,
      general practitioners (GPs) and their patients. Semistructured interviews (n =
      39) and focus groups (2 groups with specialists; 6 groups with GPs) were used to
      collect data to explore participants' views on the educational aspect of joint
      teleconsultations, and to seek examples of learning that had taken place. The
      results showed that the teleconsultation was a complex situation in which some
      learning took place for the generalists, but overall participants were
      disappointed. Three themes emerged that could enhance the educational potential
      in future: generalists' reasons for referral as an influence on perceived
      learning; lack of clarity among clinicians regarding their role and conduct; and
      the presence of patients as an inhibitor in doctor-doctor interactions.

PMID- 16884570
TI  - A qualitative study of communication during joint teleconsultations at the
      primary-secondary care interface.
AB  - It has been suggested that joint teleconsultations can improve communication at
      the primary-secondary care interface. We examined data from a qualitative
      analysis of social interactions in teleconsultations between specialists and
      general practitioners. The primary interaction was between specialists and
      patients. The general practitioners mostly adopted a 'back seat role', listening
      and observing, but not becoming actively involved. Teleconsultations create a
      number of interactional difficulties, which are likely to impede implementation
      and sustainability.

PMID- 16884571
TI  - Recruitment difficulties in a home telecare trial.
AB  - We analysed the difficulties encountered in recruiting predominantly older
      patients, suffering from an acute exacerbation of a chronic illness, to a
      randomized controlled trial of home telecare. Of 653 patients approached for
      study participation, after full assessment, 80% (519) met the trial eligibility
      criteria. Of these, 104 (20%) consented to study participation and 415 (80%)
      refused. A logistic regression model was constructed to examine independent
      effects of patient factors on probability of trial participation. Only two
      independent variables were associated with decreased likelihood of consent:
      increasing age (1 year older: odds ratio [OR] = 0.96); and being on inhaled
      steroid medication (OR = 0.60). The most common reason for refusal to
      participate, accounting for almost one-third of respondents, was a stated
      preference for a face-to-face nurse visiting service rather than a telecare
      service. Perhaps home telecare services should continue to be targeted at the
      more stable chronically ill population and not at those suffering from acute
      illness.

PMID- 16884572
TI  - An economic evaluation of Japanese telemedicine, focusing on teleradiology and
      telepathology.
AB  - We collected information by postal survey from 622 medical institutions reported
      to be using telemedicine in Japan. The questionnaire asked about willingness to
      pay (WTP) for telemedicine and willingness to undertake (WTU) it. The Kernel
      Estimation Method was used to obtain WTP for teleradiology (4379 yen),
      telepathology (9526 yen), teleconferencing (2084 yen) and teleconsultation (633
      yen). The estimated WTU were teleradiology (3875 yen), telepathology (17,918
      yen), teleconferencing (3230 yen) and teleconsultation (3643 yen). These values
      are larger than the current charges that customers actually pay or providers
      receive. Multiplying these values by the number of medical institutions that had
      implemented telemedicine allows the total annual benefits of telemedicine to be
      estimated, e.g. for teleradiology, the annual benefit in terms of WTP and WTU
      (millions of yen per year) were 140.20 and 1101.75, respectively. Based on the
      results of the survey, specific policy measures to promote telemedicine further
      include improvement of quality and reimbursement.

PMID- 16884573
TI  - Tele-treatment of patients with amyotrophic lateral sclerosis (ALS).
AB  - Management of patients with amyotrophic lateral sclerosis (ALS) mainly consists
      of (psycho) social support and advice on activities of daily living. We evaluated
      the effects of tele-treatment in addition to the conventional method of care in
      four patients with ALS. A Web application was built with information about ALS
      and a link to the tele-treatment environment. The latter contained a chat room
      and a link to start personal computer (PC)-based videoconferencing with a
      rehabilitation physician. The effect on quality of care was evaluated by
      questionnaires and interviews. The interviews showed that patients were satisfied
      with tele-treatment and experienced a pleasant contact during teleconsultations.
      The rehabilitation physician experienced acceptance of tele-treatment by the
      patients and a decrease in the time needed for travelling. Tele-treatment was
      especially suitable for discussing the practical issues about ALS. On the other
      hand, psychosocial and emotional issues still needed to be discussed during
      traditional face-to-face contact. Therefore tele-treatment should only be given
      in addition to face-to-face contact, rather than as a replacement for it.

PMID- 16884574
TI  - Management of medicines information for patient safety.
AB  - Ensuring patient safety in the management of medicines requires the efficient
      collection, administration, analysis and distribution of huge amounts of data
      from different sources. This requires the development of generic methods and
      tools for tasks such as: (1) data mining and semantics-based inference; (2)
      integration of heterogeneous scientific information databases relating to drugs
      and diseases; (3) terminology and coding issues; (4) adverse drug events and
      signal detection; and (5) networking and security. Collaborative research and
      development will be required to develop coordinated health care information
      services. Easy access to high-quality information will provide better health care
      and increased cost efficiency.

PMID- 16884575
TI  - The use of information technologies for diagnosis in ophthalmology.
AB  - In 2003, a health IT programme for clinical decision support started in
      Lithuania. An initial goal was to create databases for ophthalmology images and
      to develop processing algorithms to extract diagnostically valuable information
      from images. We have investigated how vectors, consisting of the parameters
      derived from fundus images, are distributed and whether they form specific
      groups. When analysing the multidimensional patient data vectors, comprising all
      the 27 image parameters, it was impossible to separate the healthy eyes from the
      diseased ones. However, it was possible to simplify the system by eliminating
      redundant parameters and introducing new ones that represent a subset of
      parameters from the initial group. Thus it may prove possible to identify
      glaucoma using this system of parameters.

PMID- 16884576
TI  - Evaluation of a mobile health system for supporting postoperative patients
      following day surgery.
AB  - A system based on mobile phones with built-in cameras has been developed for the
      postoperative management of patients sent home after day surgery. The system
      allows patients to send pictures and pulse oximetry measurements to a hospital
      server in a few seconds. Health professionals can then see what patients are
      describing and make a more objective estimate of the patients' status. Over a
      five-month period, a total of 49 patients used the system. A total of 222 images
      were sent, the average image delivery time being 29 s (SD 11). In nine cases
      (18%), the availability of images modified the treatment, and a visit to an
      emergency unit was avoided in eight of them who had blood-stained dressings and
      normal haematomas. The patients who had their treatment modified sent more images
      (an average of 5.4/patient) than those for whom images confirmed the correct
      treatment (3.1/patient). Each telephone call lasted for a mean duration of 18 min
      (range 8-34). The patient satisfaction data showed that all the aspects studied
      were evaluated in a very positive way, with 96% of the patients completely
      satisfied with the attention received by the mobile health application.

PMID- 16884577
TI  - Integration of monitoring and motor-training units for a tele-rehabilitation
      service.
AB  - A tele-rehabilitation system has been designed for general use. The service can
      extend the rehabilitation treatment of patients affected by neurological diseases
      such as stroke or multiple sclerosis to their home, while under the control,
      supervision and responsibility of a hospital. Part of the initial work involved
      identifying the functional blocks of a tele-rehabilitation service. There are
      three parties involved in the tele-rehabilitation service: the health provider
      (the central unit of the system), the health operator (the medical unit of the
      system, generally a therapist) and the home platform (a central console with a
      high level of modularity). Tele-rehabilitative services that are easy to use
      could radically change the routine care and rehabilitation process.

PMID- 16884578
TI  - Chronic heart failure home-based management with a telecardiology system: a
      comparison between patients followed by general practitioners and by a cardiology
      department.
AB  - A group of patients with chronic heart failure (CHF) were followed by general
      practitioners (GPs) with a telecardiology system, and a second group of patients
      were followed by a home-based telemonitoring (HBT) protocol with medical and
      nursing supervision. The 212 GP patients were older than the 226 HBT patients,
      mostly women, with CHF secondary to chronic hypertension, less self-sufficient
      and with a non-optimized therapy. The mean number of telephone calls was 2.6 per
      patient in the GP group and 16.6 per patient in the HBT group (P<0.001). These
      preliminary data suggest the applicability and the efficacy of both management
      models for CHF patients.

PMID- 16884579
TI  - A comprehensive e-education engine for a virtual diabetes centre.
AB  - It seems likely that the development of effective diabetes education for
      patients, carers and staff would prove highly cost-effective. Diabetes-e is an
      electronic diabetes encyclopaedia designed to provide comprehensive education to
      patients, carers (e.g. family, schools, care homes) and health professionals
      (specialist and non-specialist). In addition, educational media such as
      information leaflets (that can be printed during a consultation), streaming
      educational video and slide resource packs are available. Self-assessment
      questionnaires with feedback guide further education and facilitate targeted
      continuing professional development (CPD) for health professionals. The prototype
      has been developed with a particular emphasis on patient input. It is anticipated
      that Diabetes-e will be implemented across Central Nottinghamshire, including
      training of key personnel, by the end of 2005. The project has already gone live
      for insulin commencement.

PMID- 16884580
TI  - Artificial feedback for remotely supervised training of motor skills.
AB  - Electromyographic (EMG) biofeedback can be used to train motor functions at a
      distance, which makes therapy at home a possibility. To enable patients to train
      properly without the presence of a therapist, artificial feedback is considered
      essential. We studied the combined effect of age and timing of artificial
      feedback on training muscle relaxation in 32 healthy subjects (younger: 20-35
      years; older: 55-70 years). All subjects improved their performance significantly
      (F = 6.1, P<0.001). The effect of different timing of feedback (feedback provided
      during or after performance) was similar in young and older adults. However, this
      conclusion should be interpreted with caution owing to the small sample size. It
      can be argued that the artificial feedback used was too complicated for older
      adults to interpret. When designing remotely supervised treatment programmes, one
      should consider carefully the way that artificial feedback is being applied as it
      may enable (elderly) subjects to train without the presence of a therapist.

PMID- 16884581
TI  - A randomized controlled trial of an interactive Web-based intervention for
      reducing alcohol consumption.
AB  - In an uncontrolled pilot study of an interactive, Web-based treatment programme
      for people with alcohol problems, the mean number of units consumed decreased
      from 33 per week to 23. A two-arm online randomized controlled trial will be
      conducted to determine the effectiveness of an interactive Web-based intervention
      for reducing alcohol consumption. Participants will be randomized to intervention
      (access to an interactive Web-based intervention plus information) or control
      (access to an information Web-site only) groups, and followed up for six months.
      The primary outcome measure will be reduction in units of alcohol consumed in the
      previous seven days; secondary outcome measures will determine effects on alcohol
      dependence, alcohol-related harm and social disruption and quality of life.
      Recruitment, consent, randomization, intervention and follow-up will all be
      delivered on-line.

PMID- 16884582
TI  - Diabetes education via mobile text messaging.
AB  - Living with diabetes makes great educational demands on a family. We have tested
      the feasibility of using the mobile phone short message service (SMS) for
      reaching people with diabetes information. We also assessed user satisfaction and
      perceived pros and cons of the medium through interviews. Eleven parents of
      children with type 1 diabetes received messages for 11 weeks. The parents were
      positive about the system and said that they would like to continue to use it.
      The pop-up reminding effect of SMS messages in busy everyday life was noted as
      positive. Some parents experienced the messages as somewhat intrusive, arriving
      too often and at inconvenient times. The parents also noted the potential of the
      messages to facilitate communication with their adolescent children. The
      inability to store all of the messages or to print them out were seen as major
      disadvantages. Overall, the SMS seems to hold promise as means of delivering
      diabetes information.

PMID- 16884583
TI  - An assessment of parental satisfaction with mode of delivery of specialist advice
      for paediatric cardiology: face-to-face versus videoconference.
AB  - Comparisons of parental satisfaction were made after specialist paediatric
      cardiology consultations were conducted either by conventional face-to-face
      delivery or telemedicine. Satisfaction statements were rated by 100 parents: 20
      who experienced telemedicine; 56 with new children seen in the outreach clinics;
      24 with children on review whose next appointment was at the specialist centre.
      There was general satisfaction with both types of consultations, but significant
      differences were noted. Those who had videoconferences felt that they had
      received an explanation about how the specialist advice would be obtained, and
      that they could see the pictures being discussed clearly. Those who had
      experienced telemedicine believed that teleconsultations could save them
      travelling time and money and they found the technical aspects of sound and
      picture quality acceptable. They were not discomforted by the technology and felt
      reassured by the consultation with the specialist. However, there was some
      ambivalence towards the statements suggesting that teleconsultations could take
      the place of conventional face-to-face consultations.

PMID- 16884584
TI  - Analytical microextraction: current status and future trends.
AB  - Analytical microextractions, defined as nonexhaustive sample preparation with a
      very small volume of extracting phase (microliter range or smaller) relative to
      the sample volume, represent an important development in the field of analytical
      chemistry. Analytes are extracted by a small volume of a solid or semi-solid
      polymeric material, as in solid-phase microextraction (SPME), or alternatively by
      a small volume of a liquid, as in liquid-phase microextraction (LPME). This paper
      gives an overview of the SPME and LPME techniques and discusses future trends.
      This includes a discussion of the different extraction formats available,
      commercial equipment, method transfer from traditional sample preparation methods
      to microextraction, and performance as well as robustness for the latter type of
      systems. In addition, the paper contains a unified approach to the understanding
      of extraction thermodynamics and kinetics applicable to both SPME and LPME.

PMID- 16884585
TI  - Experiences with carrier-mediated transport in liquid-phase microextraction.
AB  - Different organic borates, phosphates, sulphates, and carboxylic acids are
      evaluated as extraction carriers in three-phase liquid-phase microextraction
      (LPME). Hydrophilic basic drugs form ion-pairs with the carriers and are
      extracted as ion-pair complexes into an organic liquid membrane of n-octanol or
      peppermint oil immobilized in the pores of a polypropylene hollow fiber. From
      this point, the basic drugs are released into a 20-microL solution of 50mM HCl
      placed inside the lumen of the hollow fiber (acceptor solution). Simultaneously,
      the carrier is neutralized by protons from the acceptor solution (protonated to
      maintain the charge balance). Both water-soluble and water-insoluble carriers are
      tested. One promising candidate among the water-soluble carriers is 1
      heptanesulfonic acid. This is added to the sample solution to a final
      concentration of 25mM and served to ion-pair the analytes within the sample
      solution. Among the less water-soluble candidates, a mixture of di(2-ethylhexyl)
      phosphate (DEHP) and tris(2-ethylhexyl) phosphate (TEHP) serve as efficient
      carriers. Ten percent (w/w) of each of DEHP and TEHP are added to the organic
      liquid membrane, and these carriers principally worked through ion-pairing with
      the analytes at the interface between the sample solution and the organic liquid
      membrane. Several carriers are found to be compatible with human plasma samples,
      and bromthymol blue is particularly efficient in combination with these protein
      containing matrices. Following optimization of the conditions for bromthymol
      blue, including saturation of the plasma samples with sodium sulphate, extraction
      recoveries between 45% and 75% are obtained for eight model drugs after 60 min of
      extraction. With bromthymol blue as the carrier, highly acceptable validation
      data are obtained for phenylpropanolamine and practolol extracted from human
      plasma.

PMID- 16884586
TI  - Field sampling with a polydimethylsiloxane thin-film.
AB  - In this research, field samplers are developed using polydimethylsiloxane (PDMS)
      thin-film as the extraction phase. This technique is based on a similar theory,
      the solid-phase microextraction (SPME) technique. More specifically, the
      development of the field sampler involves cutting a section of PDMS thin-film
      into a specific size and shape, and mounting it onto a stainless steel wire (the
      handle). The thin-film is then placed into a protective copper cage prior to
      deployment to prevent biofouling. Kinetic calibration or equilibrium calibration
      with the standards in the extraction phase is used to introduce an isotopically
      labeled internal standard for on-site calibration. The initial loading of the
      standard onto the thin-film and the amount of standard remaining on the thin-film
      are determined using gas chromatography-mass spectrometry and subsequently used
      to estimate the concentration of the target analytes. In addition, the field
      samplers are deployed in the field at two locations (the Meuse River in Eijsden,
      The Netherlands from April to May, 2005 and Hamilton Harbour located at the
      western tip of Lake Ontario, ON, Canada from September to December, 2006).
      Polycyclic aromatic hydrocarbons are identified, and concentrations of
      fluoranthene and pyrene are estimated in the low ng/L range. The results from
      both sampling sites are within the expected ranges for environmental samples.
      This polymeric extraction phase has a high surface-to-volume ratio compared with
      SPME, which results in higher sensitivity and mass uptake, leading to the
      detection of lower levels of analytes that many other techniques are unable to
      achieve.

PMID- 16884587
TI  - Progress of solid-phase microextraction coatings and coating techniques.
AB  - Solid-phase microextraction (SPME) has been popular as an environmentally
      friendly sample pretreatment technique to extract a very wide range of analytes.
      This is partly owing to the development of SPME coatings. One of the key factors
      affecting the extraction performances, such as the sensitivity, selectivity, and
      reproducibility, is the properties of the coatings on SPME fibers. This paper
      classifies the materials used as SPME coatings and introduces some common
      preparation techniques of SPME coating in detail, such as sol-gel technique,
      electrochemical polymerization technique, particle direct pasting technique,
      restricted access matrix SPME technique, and molecularly imprinted SPME
      technique.

PMID- 16884588
TI  - Development of an impregnated reagent and automation of solid-phase analytical
      derivatization for carbonyls: proof of principle.
AB  - This study undertakes reduction of scale and automation of a solid-phase
      analytical derivatization of carbonyls with 2,4-dinitrophenylhyrazine on a
      styrene-divinylbenzene resin (XAD-2). Three processes are tested. In the batch
      process, an aqueous phase consisting of 50 microL of sample and 150 microL of
      reagent solution is contacted with 6 mg XAD-2 by shaking. An impregnated reagent
      consisting of 2,4-dinitrophenylhydrazine hydrochloride (DNPH) deposited on XAD-2
      enables two additional processes. In-vial derivatization with an impregnated
      reagent requires shaking 50 microL of sample with 6 mg of the impregnated reagent
      and reduced the reaction time from 10 to 5 min. The third process involves
      packing impregnated reagent a mini-column and flowing 50 microL of sample through
      under positive pressure supplied by a Harvard Pump. This reduces sample
      preparation time to 1 min. Studies are conducted with worst-case model analytes:
      butanone, 2-pentanone, and malonyldialdehyde. The carbonyl of the two ketones is
      hindered, and, thus, these two compounds react very slowly with DNPH in aqueous
      solution. Malonyldialdehyde is highly water soluble, and it does not react in
      aqueous phase but also would not sorb onto XAD-2 for reaction. Nevertheless,
      derivatization/extraction of all model compounds any of the three procedures
      result in reproducible and high yields.

PMID- 16884589
TI  - Optimization of the SPME parameters and its online coupling with HPLC for the
      analysis of tricyclic antidepressants in plasma samples.
AB  - Solid-phase microextraction (SPME)-liquid chromatography (LC) is used to analyze
      tricyclic antidepressant drugs desipramine, imipramine, nortriptyline,
      amitriptyline, and clomipramine (internal standard) in plasma samples. Extraction
      conditions are optimized using a 2(3) factorial design plus a central point to
      evaluate the influence of the time, temperature, and matrix pH. A
      Polydimethylsiloxane-divinylbenzene (60-mum film thickness) fiber is selected
      after the assessment of different types of coating. The chromatographic
      separation is realized using a C(18) column (150 x 4.6 mm, 5-microm particles),
      ammonium acetate buffer (0.05 mol/L, pH 5.50)-acetonitrile (55:45 v/v) with 0.1%
      of triethylamine as mobile phase and UV-vis detection at 214 nm. Among the
      factorial design conditions evaluated, the best results are obtained at a pH
      11.0, temperature of 30 degrees C, and extraction time of 45 min. The proposed
      method, using a lab-made SPME-LC interface, allowed the determination of
      tricyclic antidepressants in in plasma at therapeutic concentration levels.

PMID- 16884590
TI  - HS-SPME determination of volatile carbonyl and carboxylic compounds in different
      matrices.
AB  - Specific chromatographic methodologies are developed for the analysis of
      carboxylic acids (C(2)-C(6), benzoic) and aldehydes (C(2)-C(10)) of low molecular
      weight in diverse matrices, such as air, automotive exhaust gases, human breath,
      and aqueous matrices. For carboxylic acids, the method is based on their reaction
      with pentafluorobenzyl bromide in aqueous solution, followed by the separation
      and identification of the resultant pentafluorobenzyl esters by means of
      headspace (HS)-solid-phase microextraction (SPME) combined with gas
      chromatography (GC) and electron capture detection (ECD). Detection limits in the
      microg/m(3) range are reached, with relative standard deviation (RSD) less than
      10% and linear response (R(2) > 0.99) over two orders of magnitude. The
      analytical methodology for aldehydes is based on SPME with simultaneous
      derivatization of the analytes on the fiber, by reaction with
      pentafluorophenylhydrazine. The derivatization reagent is previously deposited on
      the SPME fiber, which is then exposed to the gaseous matrix or the HS of the
      sample solution. The pentafluorophenyl hydrazones formed on the fiber are
      analyzed selectively by means of GC-ECD, with detection limits in the ng/m(3)
      range, RSD less than 10%, and linear response (R(2) > 0.99) over two orders of
      magnitude.

PMID- 16884591
TI  - Solid-phase microextraction coupled with liquid chromatography for determination
      of beta-carotene in food.
AB  - Beta-carotene in vegetables and nutritional products is analyzed using solid
      phase microextraction (SPME) coupled with liquid chromatography (LC) to improve
      the speed of analysis and to reduce the consumption of organic solvents. The
      relative standard deviations (RSDs) of this analytical method for beta-carotene
      determinations in vegetables and nutritional products are approximately 10% and
      5%, respectively. The amount of beta-carotene was found to vary from 0.35 +/-
      0.05 ppm to 76.5 +/- 6.9 ppm for several vegetables in Taiwan. This method was
      linear over the range of 0.4-40 ppm with correlation coefficients higher than
      0.997. The experimentally determined level of beta-carotene in nutritional
      products varied from 3.8 +/- 0.2 ppm to 24.6 +/- 1.1 ppm following SPME-LC. The
      recoveries of beta-carotene for these measurements following SPME were all higher
      than 97% +/- 2% (n = 3). The detection limits of beta-carotene for this method
      were from 0.027 to 0.054 ppm. Conventional solvent extractions take approximately
      4-6 h for extraction and reconcentration but SPME takes approximately 1 h. From
      several tens to hundreds of milliliters, organic solvents can be saved using
      SPME. SPME provides better analyses on beta-carotene than conventional solvent
      extraction for nutritional products in terms of speed, precision, simplicity, and
      solvent consumption.

PMID- 16884592
TI  - Determination of microcystins in water using integrated solid-phase
      microextraction with microbore high-performance liquid chromatography
      electrospray quadruple time-of-flight mass spectrometry.
AB  - The development of a technique combining solid-phase microextraction (SPME) with
      microbore high-performance liquid chromatography (micro-HPLC)-tandem quadrupole
      time-of-flight (QTOF) mass spectrometry (MS) for determination of dissolved
      microcystins in water is reported. Several important parameters affecting the
      efficiency of SPME extraction of microcystins are investigated. A microbore C18
      column HPLC coupled with tandem QTOF-MS with information-dependent acquisition
      (IDA) is developed to effectively analyze microcystins in microliter volumes of
      SPME extracts. The micro-HPLC-QTOF-MS with IDA technique provides comprehensive
      information, including a survey chromatogram (total ion chromatogram), full scan
      mass spectrum, and product ion scan mass spectra at different collision energies
      for individual analytes, which allows for both identification and quantitation in
      the same run. Linear calibration curves of microcystin standard [microcystin (MC)
      arginine (R)R] 1-100 microg/L and of microcystin standard [MC-leucine (L)R] 1-250
      microg/L are obtained with a correlation coefficient of 0.996. The combination of
      SPME with HPLC-QTOF-MS and IDA offers limits of detection of 0.6 pg for MC-RR and
      1.6 pg for MC-LR. Analysis of spiked lake-water samples shows a recovery of > 86%
      for MC-RR and > 70% for MC-LR. This technique requires small sample volumes,
      minimizes the use of organic solvents, and provides sensitive and information
      rich analysis of unknown samples.

PMID- 16884593
TI  - Online coupling of solid-phase microextraction and capillary electrophoresis.
AB  - Solid-phase microextraction (SPME) and capillary electrophoresis (CE) are two of
      the main inventions that shaped 20th Century analytical chemistry. SPME is an
      effective microscale sampling and sample preparation technique, and CE is a high
      efficiency microanalytical method. Online coupling of SPME with CE can be a
      powerful combination because of the significant advantages of the two techniques.
      The progress in the development of online SPME-CE coupling is surveyed in this
      review. Problems encountered and solutions reported are highlighted.

PMID- 16884599
TI  - Pigmented mesenteric lymphadenopathy in familial adenomatous polyposis - an
      unusual cause of intraoperative abandonment of ileo-anal pouch.
AB  - Familial adenomatous polyposis (FAP) is an autosomal dominant condition with near
      complete penetrance, characterised by the presence of numerous adenomatous polyps
      of the colon and rectum. Melanosis coli describes the brownish-black
      discolouration of the colon resulting from the accumulation of a granular pigment
      in the phagosomes of macrophages in the colonic lamina propria. The presence of
      melanosis pigment in pericolonic lymph nodes has been reported in patients with
      coincidental melanosis coli, following segmental colonic resection. We report a
      unique case of FAP with melanosis pigment in lymph nodes in the small bowel
      mesentery that initially prevented a restorative proctocolectomy but that
      resolved following a colectomy, subsequently facilitating formation of an ileo
      anal pouch.

PMID- 16884600
TI  - Penile skin necrosis - complication following selfcircumcision.
AB  - Circumcision is one of the commonest operations performed throughout the world
      for ritual, traditional or medical reasons. Self-circumcision may lead to
      disastrous complications. There have been reports of the complications following
      use of the constricting devices for improved sexual performance and for auto
      erotic intentions, but cases of self-circumcision leading to complications such
      as necrosis of the penile skin and strangulation of the penis are very rarely
      reported. This case represents penile skin necrosis in a 55-year-old white
      English man following an attempt at self-circumcision with a medically unapproved
      plastic device available in the market. He recovered after surgical debridement
      and treatment with antibiotics.

PMID- 16884603
TI  - NICE Health Technology Appraisal Programme.

PMID- 16884606
TI  - Mesenteric fibromatosis: a rare cause of acute abdominal pain.
AB  - A 45-year-old man, with a previous history of astrocytoma, presented with diffuse
      abdominal pain. A CT scan was non-specific and the pain worsened; his abdomen
      became peritonitic on examination. An exploratory laparotomy was performed, and a
      large small bowel mesenteric mass was found together with an associated
      haematoma. Subsequent histology showed the tumour to be a benign fibromatosis,
      and the patient recovered uneventfully. There were no reports in the literature
      of any association between astrocytomas and fibromatosis. Mesenteric fibromatosis
      is a rare tumour often associated with Gardner's syndrome. It can present in a
      multitude of ways and the only definite treatment is surgical resection.

PMID- 16884607
TI  - Scapular fracture after electric shock.
AB  - Scapular fracture as a direct result of electric shock is a rare injury. We
      present a case report and review of the literature.

PMID- 16884612
TI  - Increase in hospital mortality from non-communicable disease and HIV-related
      conditions in Bulawayo, Zimbabwe, between 1992 and 2000.
AB  - The HIV/AIDS pandemic is creating a strain on health care services in the
      developing world, with knock-on consequences for HIV negative patients. We looked
      for possible changes over time in the patterns of illness and outcomes of
      admission to an adult medical unit in Zimbabwe. We performed a prospective
      descriptive study of discharge diagnoses and causes of in-hospital ;mortality for
      all medical patients under the care of one consultant at Mpilo Central Hospital,
      Bulawayo, Zimbabwe. Two similar 7-month periods were compared in 1992 and 2000.
      Data recorded included: initials, sex, alive or dead status, diagnosis and
      HIV/AIDS status. Similar numbers of patients were admitted in 1992 and 2000 (1305
      and 1369), but in-hospital mortality increased from 13.3% to 28.6% (P < 0.001),
      especially in male patients (13.1% to 33.9% P < 0.001). Mortality rates increased
      for both infectious and non-communicable diseases such as cardiac failure, stroke
      and diabetes. The 10 most common diagnoses were similar, apart from Pneumocystis
      carinii pneumonia (PCP) cases, which increased from 18 to 90. The proportion of
      patients clinically or serologically positive for HIV/AIDS rose from 13.9% to
      51.1% (P < 0.001), but the number of cases of the HIV wasting syndrome
      (SLIM)/chronic gastroenteritis did not change significantly. In 1992 there
      happened to be a large number of cases of malaria transmission. Mortality related
      to both communicable and non-communicable diseases increased, confirming that HIV
      negative patients are also being affected by the strain on health services.
      Although based on clinical and radiological diagnosis, PCP pneumonia appears to
      be increasingly common in this area.

PMID- 16884613
TI  - Exemption policies and community preferences for tropical endemic diseases in the
      Bamako initiative programme in Nigeria.
AB  - We determined the actual written policies/guidelines and practices of fee
      exemptions aimed at the primary health-care level for tropical diseases treatment
      within the Bamako initiative system and the community's and decision makers'
      preferences for exemption in Nigeria. Health policy documents from the federal
      and state ministries of health were reviewed to determine the guidelines for
      exemptions, services, goods and category of people to receive exemptions. The
      records of the local government areas, health centres and community health
      committees were also reviewed to check who had received exemptions and modalities
      for doing so. In addition, household surveys using questionnaires was conducted.
      There is no clear-cut national policy regarding exemption. In areas where
      exemption exists, these are largely unofficial, as no official documents exist to
      support exemption. A total of 1594 individuals were surveyed. Community members
      prefer pregnant women, children and patients with TB, malaria, onchocerciasis and
      leprosy to be exempted from payment of fees: decision makers prefer the poor,
      children and patients with malaria, TB and leprosy to be exempted from payment
      for drugs, registration, consultation and preventive services such as
      immunization and antenatal services. One area of divergence between the
      preferences of the community and decision makers is the issue of exempting people
      with malaria and HIV/AIDS.

PMID- 16884614
TI  - Child sexual abuse and its outcomes among high school students in southwest
      Ethiopia.
AB  - Child sexual abuse (CSA) is a major contributing factor to the burden of disease
      among children and adolescents. The aim of this study is to determine the
      prevalence of CSA and its outcomes among female high school students in Ethiopia.
      A cross-sectional study was conducted among Jirren high school female students in
      April 2005. A total of 323 female students from grade 9 were selected by
      systematic random sampling and they completed a self-administered questionnaire
      on experiences of sexual abuse. Data were cleaned and analysed by SPSS/PC
      statistical package. The results revealed that the prevalence of CSA was 68.7%.
      Among the different forms of sexual abuses, verbal harassment was the most common
      (51.4%) followed by sexual intercourse, 18.0% and unwelcome kissing, 17.1%. The
      commonly indicated abusers in this study were unknown persons (36%) followed by
      school-mates (31.5%). Among victims of sexual abuse, 7.2% had an unwanted
      pregnancy and 5.9% had sexually transmitted diseases. The rate of other
      psychological effects of CSA, such as suicide ideation, suicide attempt, and
      sexual dysfunction, was high. The overwhelming majority (86.4%) considered sexual
      abuse to be a major social problem. The study revealed that the prevalence of CSA
      is high. Reproductive health education should be provided to students. Parents,
      police, and the public in general should be made aware of the problem before it
      endangers the lives of children and adolescents.

PMID- 16884615
TI  - Knowledge and practice of help-seeking for treatment of mental disorders in Pemba
      Island, Zanzibar.
AB  - The objective of this study was to describe how people explain mental disorders
      and its treatment in Pemba Island, Zanzibar. Eight hundred and twenty-one
      participants (users, carers, health professionals, traditional healers, community
      members and leaders) were interviewed as part of a cross-sectional survey. Most
      people viewed mental disorder as arising within their internal or supernatural
      world. Although they thought that they could be helped both by primary health
      care and alternative healing, the majority described going to the traditional
      healers when things went wrong. This provides evidence that there is considerable
      reliance on traditional care for the treatment of mental disorders. It is
      therefore important for the health services to be in dialogue with the
      traditional healers.

PMID- 16884616
TI  - Co-agglutination test for cysticercus antigen detection in the serum for the
      diagnosis of cysticercosis.
AB  - The objective of the study was to develop the co-agglutination (Co-A) test, a
      rapid slide agglutination test for the diagnosis of cysticercosis. The present
      study included 21 cases of cysticercosis, which comprised seven cases of clinico
      radiologically definite cases of neurocysticercosis (NCC) proven with either
      computed tomography (CT) scan or magnetic resonance imaging (MRI), eight cases of
      clinically strong NCC, six cases of extraneural cysticercosis in muscle and eye;
      40 non-cysticercal parasitic infection controls; and 20 healthy controls.
      Hyperimmune cysticercus antiserum was raised in rabbits and was used to coat
      Staphylococcus aureus (Cowan strain-I) bearing protein A (SAPA) cells, and the Co
      A was standardized to detect cysticercal antigen in the serum. Serum samples from
      12 out of 21 (57%) cases of cysticercosis were positive for cysticercal antigen
      by the Co-A test. Of the 12 positive samples, eight were from cases of
      neurocysticercosis and four from cases of extra-neural cysticercosis. Serum
      samples from seven out of 40 non-cysticercal parasitic infection controls and
      serum samples from one out of 20 (5%) healthy controls showed a false-positive
      reaction for the antigen by the Co-A test. There was a statistically significant
      difference between the antigen detection rates among cysticercosis patients on
      one hand, and the patients with other parasitic diseases (P = 0.0014), and
      healthy controls (P=0.0003) on the other. The Co-A test appears to be a
      moderately sensitive and specific test for the diagnosis of cysticercosis.

PMID- 16884617
TI  - Anaesthesia for elective inguinal hernia repair in rural Ghana - appeal for local
      anaesthesia in resource-poor countries.
AB  - Local anaesthesia has been identified as the most favourable anaesthesia for
      elective inguinal hernia repair with respect to complication rate, cost
      effectiveness, and overall patient satisfaction. Operation theatre notes in all
      seven hospitals in the Northern Region in Ghana over the period of 1 year were
      reviewed. Only 22.4% out of 1038 repairs were performed under local anaesthesia
      while predominantly spinal and general anaesthesia were used (48.0 and 29.6%,
      respectively). African surgeons chose local anaesthesia far less frequently than
      visiting overseas surgeons (15.6 versus 27.7%, respectively). All surgeons in
      resource-poor countries should be encouraged to use local anaesthesia more
      frequently for elective inguinal hernia repair. Valuable resources in sub-Saharan
      African hospitals could be saved, especially if used in combination with
      outpatient surgery. The technique should be taught in teaching institutions. A
      simple step-by-step technique is described.

PMID- 16884618
TI  - International health links: an evaluation of partnerships between health-care
      organizations in the UK and developing countries.
AB  - Increasingly, international health links are evolving between UK health-care
      institutions and those in developing countries, the core aims of which are to
      seek the transfer of ideas, knowledge, skills and training. This study aimed to
      evaluate established health links, what constitutes them and how they are
      supported. Benefits and challenges associated with the links, as perceived both
      by link coordinators in the UK and their overseas partners, were explored.
      Fourteen links between health-care organizations in the UK and those in
      developing countries were identified and interviews were successfully conducted
      with 22 link coordinators: 13 in the UK and nine in developing countries. The
      interviews indicated that health links offer mutual benefits to both partners in
      terms of shared skills and the promotion of global awareness. Links can act as
      important catalysts; stimulating increases in institutional capacity for research
      and training. They provide opportunities for personal and professional
      development of staff and promote the development of friendships and supportive
      networks between diverse communities. Many of the health links showed signs of
      evolving from uniprofessional links between individual institutions into broader,
      multidisciplinary community partnerships. The main challenges facing health links
      arise from cultural differences, funding problems, communication difficulties and
      bureaucracy. There was broad agreement that greater recognition of the value and
      importance of health links by the NHS and closer collaboration between government
      departments to provide support and resources could promote wider and more
      effective link partnerships.

PMID- 16884619
TI  - Using fishing line for suturing.
AB  - Fishing line is an inexpensive and atraumatic suture material. Its properties and
      uses are summarized here. Comparison is made between different diameters and
      types of fishing line and commercially available sutures and needles to enable
      appropriate line selection for its use as suture material.

PMID- 16884620
TI  - Clinico-pathological patterns of squamous cell carcinoma in Nigeria.
AB  - Squamous cell carcinoma (SCC) is the second most common form of skin cancer and
      frequently arises in the sun-exposed skin of middle-aged and elderly individuals.
      We retrospectively reviewed 443 patients managed for SCC (cutaneous and non
      cutaneous) in our hospital from January 1979 to December 2002. The age
      distribution showed peak incidence between fourth and sixth decades of life. The
      duration of symptoms ranged from 6 months to 552 months (standard deviation [SD]
      = 54.29), while the head and neck region was the most common site of cutaneous
      SCC. SCC is not rare in our environment. Patients with skin lesions are advised
      to present early to their physician for early diagnosis and appropriate
      treatment.

PMID- 16884621
TI  - A national survey of surgical activity in hospitals in Malawi.
AB  - Malawi is a poor country with few doctors. It has 21 district hospitals, all of
      which have operating theatres but none of which has a surgeon. Most district
      hospitals are manned by a single doctor and two or more paramedic clinical
      officers. In 2003, a total of 28,594 operations were performed in district
      hospitals. In all, 12,506 (44%) of these were obstetric or gynaecological
      procedures, but only 821 (3%) were general surgical cases. It appears that
      district clinicians are happy to attempt emergency obstetric and gynaecological
      cases but tend to refer emergency general surgical cases.

PMID- 16884622
TI  - Enterobius vermicularis causing symptoms of appendicitis in Nepal.
AB  - This study set out to determine the prevalence of Enterobius vermicularis in
      surgically removed appendices and to assess the possible relation of the parasite
      to acute appendicitis. All 624 surgically removed appendices received in the
      Department of Pathology, BPKIHS, Dharan, Nepal during 2(1/2) years (August 1999
      January 2002) were examined. E. vermicularis was identified in nine (1.62%)
      appendices from the patients with a clinical diagnosis of appendicitis. The
      parasite was most frequently seen in histologically normal appendices (6/71) and
      was rarely associated with histological change of acute appendicitis (3/539). No
      cases of E. vermicularis infestation occurred in appendices showing chronic
      inflammation or removed during the course of other surgical procedures. E.
      vermicularis was found more frequently in uninflamed and histologically normal
      appendices (8.45%) than those which were inflamed with histopathologic changes of
      acute appendicitis (0.56%). It may be a cause of symptoms resembling acute
      appendicitis although the mechanism for this does not involve mucosal invasion by
      the parasite.

PMID- 16884623
TI  - Schistosomiasis of the appendix in Maiduguri.
AB  - We retrospectively studied 27 histologically diagnosed cases of schistosomiasis
      of the appendix at the University of Maiduguri Teaching Hospital between January
      1994 and December 2003. Of 1183 cases of appendices histologically examined,
      schistosomiasis was seen in 27 (2.3%).

PMID- 16884624
TI  - Pre- and post-directly observed treatment era in the management of TB: a
      teachiing hospital experience.
AB  - The study evaluated the effect of implementing the directly observed treatment
      (DOT) programme for the treatment of TB in a teaching hospital setting in
      Nigeria. A significant increase in treatment completion rate and reduction in
      mortality was observed. The expansion of the DOT programme is desirable to stem
      the increasing TB epidemic in the country.

PMID- 16884625
TI  - Clinical and microbiological profiles of ear infections in Osogbo, Nigeria.
AB  - Despite the fact that discharging ears (DE) are one of the most common
      presentations to ear, nose and throat (ENT) clinics in the tropics, few reports
      have documented the aetiologic agents involved. The pathogenesis is therefore not
      fully understood and treatment remains controversial. We present in this report
      the microbiological characteristics of DE over a 3-year-period at the ENT clinic
      of Ladoke Akintola University Teaching Hospital, Osogbo, Southwest Nigeria.

PMID- 16884626
TI  - Prevalence of anaemia among adolescent girls in the urban slums of Vellore, south
      India.
AB  - A community-based, cross-sectional study was conducted to determine the
      prevalence of anaemia among unmarried, adolescent south Indian girls in an urban
      slum setting. A total of 100 apparently healthy girls between the ages of 11 and
      18 years were recruited. Their socioeconomic, dietary and anthropometric
      information was collected, and blood haemoglobin (Hb) was estimated. The
      prevalence of anaemia (Hb < 12 g%) was 29%. Most had mild anaemia; severe anaemia
      was not seen. Two-thirds of those with anaemia had low serum ferritin (<12
      microg/L). Significant associations were observed between anaemia and low
      socioeconomic status, religion and reporting infrequent/non-consumption of meat
      (heme iron). Only meat consumption was related to haemoglobin by multiple
      regression analysis. Anaemia is a common problem among adolescent girls in this
      setting, though severe anaemia is rare. There is a need to improve their
      haemoglobin status through dietary modification along with preventive
      supplementation and nutrition education.

PMID- 16884627
TI  - Mortality of very-low-birth-weight infants in Jamaica.
AB  - A 10-year retrospective descriptive study was conducted looking at the outcome of
      all neonates weighing less than 1500 g admitted to the University Hospital of the
      West Indies. Analysis of predictors of mortality using regression models revealed
      birth weight to be the only independent predictor of mortality. Further
      improvement in survival of these infants will be dependent on the availability of
      ventilatory and nutritional support.

PMID- 16884628
TI  - Morbidity and mortality on a paediatric ward in rural Tanzania.

PMID- 16884629
TI  - TB patients' perspectives on integrated TB/HIV services in South Africa.
AB  - There are few data describing patients' attitudes towards the integration of
      antiretroviral therapy for HIV-infected patients into existing TB services. We
      investigated this issue among patients receiving TB treatment at a primary care
      facility in Cape Town, South Africa. Of 85 patients interviewed, the vast
      majority (92%, n = 78) stated they would be willing to attend an integrated
      TB/HIV service; perceived stigmatization of TB and HIV was a significant
      predictor of negative attitudes towards a combined TB/HIV programme (adjusted
      odds ratio, 19.90, P = 0.02). While integrated TB/HIV services appear generally
      acceptable in this setting, continuing efforts to combat stigmatization are
      necessary to ensure maximum uptake.

PMID- 16884630
TI  - Myringoplasty results in a district hospital in Botswana.
AB  - This was a prospective study to determine the success rate of myringoplasty in a
      low-resource setting. Myringoplasty was performed on 85 patients and follow-up
      done for 6 months in order to determine the incidence of closure of the repaired
      tympanic membrane. The eardrum closure rate at 3 months was 88% and at 6 months
      84%. There was a 62% positive change of more than 10 dB in the pure tone averages
      of air conduction at frequencies 500, 1000 and 2000 Hz and a 24% improvement of
      less than 10 dB. This compares favourably with results from other studies.

PMID- 16884631
TI  - Life-threatening hyponatraemia and neurotoxicity during chemotherapy for
      Burkitt's lymphoma.

PMID- 16884632
TI  - Multifocal skeletal TB or disseminated bone TB.

PMID- 16884633
TI  - Intraperitoneal rupture of cysticercosal cyst mimicking appendicular perforation.
AB  - Anaphylaxis following intraperitoneal rupture of a cysticercosal cyst mimicking
      pelvic peritonitis secondary to appendicular perforation is reported. Human
      cysticercosis occurs following ingestion of Taenia solium eggs, usually from
      faecally contaminated food. A case of pelvic cysicercosis presenting with signs
      and symptoms of anaphylaxis and peritonitis is reported, with plausible
      explanations for this unusual presentation.

PMID- 16884634
TI  - Traumatic spinal cord injuries in Ile-Ife, Nigeria, and its environs.
AB  - In Ile-Ife, Nigeria, traumatic brain injuries are largely due to traffic
      accidents caused mainly by the bad maintenance of the roads and unsafe driving.
      Young men in the productive stage of their lives are those most affected. The
      resultant disabilities include quadriplegia (in more than half the patients) and
      paraplegia. The cost of treating and providing adequate facilities for these
      patients imposes a heavy economic burden upon developing countries.

PMID- 16884635
TI  - Testicular schistosomiasis simulating malignancy.

PMID- 16884636
TI  - Association between poverty and malaria in randomly selected families in Dar es
      Salaam.
AB  - The present study aimed to reveal the association between family incomes and
      status of malaria in 50 randomly selected families. Results show that there is an
      association between income poverty and malaria experiences (P < 0.05) and that
      80% of the low-income families experienced malaria while only 20% of high-income
      families had experienced malaria (P < 0.05).

PMID- 16884637
TI  - Injection safety practice among health workers in static immunization centres in
      a Nigerian urban community.

PMID- 16884638
TI  - Emerging co-infection of HIV and hepatitis B virus in far western Nepal.
AB  - We detected a prevalence (11%) of hepatitis B virus (HBV) infection among male
      adult villagers (n = 149) in far western Nepal where migration to India is
      common. Although only one migrant-returnee was infected with both HBV and HIV, co
      infection may occur more frequently in future as the HIV prevalence is high (8%).

PMID- 16884639
TI  - Aetiology of acute viral hepatitis in Andaman and Nicobar Islands, India.

PMID- 16884640
TI  - Gastrointestinal parasites in Ugandan cancer patients: a retrospective
      departmental review.
AB  - Of all cancer patients, 28% had gastrointestinal parasites of medical importance.

PMID- 16884643
TI  - AIDS and human rights research.

PMID- 16884641
TI  - Meningitis in Jamaican adults.

PMID- 16884644
TI  - Hansen's disease and its far-reaching social consequences.

PMID- 16884645
TI  - Fractures of the supraorbital rim: principles and management.
AB  - Dentists may be asked to provide consultations for patients who have sustained
      trauma to their facial structures. Supraorbital rim fractures, although uncommon,
      must be recognized and promptly referred to an oral and maxillofacial surgeon or
      other specialist skilled in the management of facial bone fractures. Supraorbital
      rim fractures commonly coexist with other craniomaxillofacial injuries,
      especially with fractures of the anterior table of the frontal sinus. In this
      article, we review the frequency, management and complications associated with
      the treatment of supraorbital rim fractures in adults. A series of 5 cases was
      reviewed; 4 of the 5 patients were male, with a mean age of 21.6 years (range 17
      28 years). All injuries involved the supraorbital rim and the anterior table of
      the frontal sinus and occurred concurrently with other facial injuries. Treatment
      ranged from conservative observation to open reduction and internal fixation of
      the fractures. No associated perioperative or postoperative complications
      occurred. The follow-up ranged from 6 months to 26 years, with satisfactory
      subjective esthetic outcomes in all cases.

PMID- 16884647
TI  - Soft tissue pediatric facial trauma: a review.
AB  - Facial soft tissue injuries are common in pediatric trauma patients. Early
      diagnosis and definitive treatment as well as good postoperative wound care are
      important when dealing with soft tissue injuries, such as facial nerve and
      parotid injuries, animal bites, avulsive skin wounds and eyelid and ear
      lacerations. Children heal quickly, but they also tend to develop hypertrophic
      scars. Proper wound management during the healing period can help to minimize the
      risk of adverse scar formation. Dentists may be involved in the initial
      assessment of these patients. Knowledge of the diagnosis and management of soft
      tissue trauma is useful when dealing with pediatric patients and their parents
      postoperatively.

PMID- 16884646
TI  - In-office iliac crest bone harvesting for peri-implant jaw reconstruction.
AB  - We describe 2 minimally invasive techniques for in-office iliac crest bone
      harvesting. The increasingly limited access to hospital operating rooms and the
      increased need for bone grafting to facilitate dental implant-related
      reconstructions have been the major impetuses behind relocating some of these
      surgeries to the out-of-hospital, in-office setting.

PMID- 16884648
TI  - Hard tissue pediatric facial trauma: a review.
AB  - Although hard tissue injuries are uncommon in the pediatric patient, dentists may
      be involved in the initial assessment of these patients. In this paper, we review
      fractures of the facial skeleton with a focus on dentoalveolar injuries.
      Minimally displaced fractures in pediatric patients can be managed
      conservatively, while displaced fractures may require open approaches and rigid
      fixation. New fixation stratagems are presented, and possible facial growth
      disturbances resulting from trauma are discussed.

PMID- 16884649
TI  - Nerve injuries after dental injection: a review of the literature.
AB  - Prolonged and possibly permanent change in sensation due to nerve damage can
      occur after dental injections. Although the condition is rare, many practitioners
      will see this form of nerve injury during their careers. The exact mechanism of
      the injury has yet to be determined, and little can be done to prevent its
      occurrence. This type of injury carries with it many functional and psychological
      implications, and referral to both dental and medical specialists may be
      necessary for continued follow-up and possible treatment.

PMID- 16884650
TI  - Cervicofacial and mediastinal emphysema complicating a dental procedure.
AB  - Cervicofacial subcutaneous emphysema is an infrequently reported sequela of
      dental surgery. It may be caused by the inadvertent introduction of air into the
      soft tissues during procedures using high-speed, air-driven handpieces or air
      water syringes. In this paper, we present a case in which subcutaneous emphysema
      developed in a middle-aged woman following routine restorative treatment. We
      review the features of the condition and its treatment and discuss means of
      prevention.

PMID- 16884651
TI  - Affordance-controlled bifurcations of action patterns in martial arts.
AB  - Effects of participant-target distance and perceived handstriking efficiency on
      emergent behavior in the martial art of boxing were investigated, revealing
      affordance-controlled nonlinear dynamical effects (i.e. bifurcations) within the
      participant--target system. Results established the existence of critical values
      of scaled distances for emergence of first time excitations and annihilations of
      a diverse range of boxing actions i.e. on the appearance and dissolution of jabs,
      hooks and uppercuts. Reasons for the action diversity were twofold: (a)
      topological discontinuous changes (bifurcations) in the number of possible
      handstrikes, i.e. motor solutions to the hitting task; (b) fine modification of
      probabilities of emergence of striking patterns. Exploitation of a
      'strikeability' affordance available in scaled distance-to-target information by
      boxers led to a diversity of emergent actions through a cascade of bifurcations
      in the task perceptual-motor work space. Data suggested that perceived efficiency
      (E) of an action changed as a function of scaled distance (D) and was correlated
      with the probability of occurrence of action patterns (P), exhibiting the
      following dependence P = P(E(D)). The implication is that probability of
      occurrence (P) depends on efficiency (E), which in turn depends on scaled
      distance (D) to the target. Accordingly, scaled distance-dependent perceived
      efficiency seems a viable candidate for a contextual (control) parameter to
      describe the nonlinear dynamics of striking actions in boxing.

PMID- 16884652
TI  - A cusp catastrophe model analysis of changes in adolescent substance use:
      assessment of behavioural intention as a bifurcation variable.
AB  - Behavioural intention was advanced as an alternative bifurcation variable to peer
      pressure in the context of a cusp catastrophe model of changes in adolescent
      substance use (Clair, 1998; Byrne, Mazanov & Gregson, 2001). Three sets of models
      were tested using data from a 12 month longitudinal study of adolescent smoking
      in Australia: the first with peer pressure only as the bifurcation term, the
      second with behavioural intention only and the third with both. In isolation both
      bifurcation variables performed similarly (adjusted-R2 and beta). In the third
      model, peer pressure edged out behavioural intention as an indicator of
      catastrophic change. Post hoc analysis revealed the polynomial and simple terms
      of initial conditions were more important than the bifurcation variable to
      explain change in smoking behaviour. This provoked a call for more work on
      finding an appropriately complex (non-straight line), theoretically justifiable
      mathematical model of adolescent substance use. Overall, behavioural intention
      was considered equivalent to peer pressure as a bifurcation variable although
      further research is needed to confirm this result.

PMID- 16884653
TI  - A self-destruction game.
AB  - A simple model of a self-destructing society is presented. It can be interpreted
      as a game with two players: the society and its sub-set which tends to destroy
      the whole society, as well as itself. The main factor taken into account in the
      model is the progress of science and technology which provides the destruction
      tools (new weapons and killing techniques), as well as tools the society can use
      to defend itself. The modeling and simulation tool is discrete-event and can be
      treated as agent-oriented, though the agent capabilities are rather simple. The
      simulation experiments show that, in the near future, this progress will become
      extremely dangerous, and it may result in the total destruction of mankind. For
      the longer time period, however, the conclusion is not so pessimistic. If the
      society survives during a certain time interval, then the probability of survival
      becomes greater for a longer time span.

PMID- 16884655
TI  - Does pharmacologic weight reduction improve blood pressure?

PMID- 16884654
TI  - Early brain damage in essential hypertension: "to have and have not"--is it
      important?

PMID- 16884656
TI  - Effects of treatment for hypertension on cognitive function in the elderly.

PMID- 16884657
TI  - The latest generation of beta-blockers: new pharmacologic properties.
AB  - beta-Blockers have generally demonstrated smaller reductions in cardiovascular
      events, compared with other antihypertensive classes, despite similar reductions
      in blood pressure. This may be due to the ineffectiveness of traditional beta
      blockers, such as atenolol, in reducing central aortic pressure, a strong,
      independent predictor of cardiovascular outcome. However, the beta-blocker class
      is heterogeneous, and some newer beta-blockers, which exhibit vasodilatory
      effects independent of beta-blockade, provide beneficial effects on arterial
      stiffness and endothelial dysfunction, which may lead to reductions in central
      aortic pressure and improvements in clinical outcomes. For example, the
      vasodilating beta-blocker nebivolol was shown to improve forearm blood flow and
      arterial stiffness and, in a large clinical study, to significantly reduce
      morbidity and mortality, independent of left ventricular ejection fraction, among
      patients with chronic heart failure. Further research is warranted to investigate
      any potential differences between traditional and newer vasodilating beta
      blockers on cardiovascular outcomes.

PMID- 16884658
TI  - Monitoring vascular health beyond blood pressure.
AB  - It is well recognized that vascular changes, including atherosclerosis, begin
      early in life as a silent, asymptomatic disease process and are associated with
      cardiovascular (CV) risk factors. Importantly, CV risk factors persist or track
      from childhood to adulthood and are predictive of CV disease risk in adults.
      Evaluation of arterial stiffness and its predictors may help identify
      asymptomatic individuals at risk, before blood pressure is elevated above an
      "arbitrary" level that we currently identify as hypertension. Currently,
      measurements of arterial stiffness are being used in the research setting and
      also as part of cardiovascular risk prediction clinics. As the various techniques
      become more widely available, it is conceivable that the measurement of arterial
      stiffness could become an important part of the routine assessment of patients in
      daily practice, as a supplement to blood pressure measurement. Measurement of
      arterial stiffness will not only be helpful in the detection of early vascular
      disease but also will be a tool in the follow-up monitoring of strategies aimed
      at preventing hypertension or reducing further progression of vascular disease
      before blood pressure elevation can be detected.

PMID- 16884659
TI  - Role of diet in hypertension management.
AB  - The prevalence of hypertension is high and increasing worldwide. Drug therapy is
      effective, but for both "prehypertensive" and treated hypertensive patients,
      lifestyle changes are also important. Dietary modification is a key part of these
      changes, although skepticism about the role of diet in determining blood pressure
      has slowed implementation of the available guidelines. However, there is now a
      large body of evidence supporting a role for dietary salt, potassium, alcohol,
      and body mass in determining blood pressure. Studies such as PREMIER have shown
      that salt restriction (<6 g/d), alcohol moderation (<2U/d in men and <1U/d in
      women), weight loss (if BMI>25), exercise, and a DASH (Dietary Approaches to Stop
      Hypertension) diet (supplying 20-30 mmol/d of potassium) can achieve decreases in
      systolic blood pressure of approximately 10 to 15 mm Hg when applied together. Of
      the dietary changes, salt intake remains the most amenable to change. But we must
      further reduce salt in processed food if it is to be part of a wider strategy to
      lower blood pressure in the general population. Nevertheless, the message to
      patients must be that dietary changes made within a concerted alteration in
      lifestyle can have a very significant impact on their blood pressure.

PMID- 16884661
TI  - Angiotensin-receptor blockers for prehypertension.

PMID- 16884660
TI  - Endothelin, the kidney, and hypertension.
AB  - The kidneys play a central role in the long-term regulation of blood pressure and
      in the pathogenesis of hypertension. A common defect that has been found in all
      forms of hypertension examined to date is a hypertensive shift in the pressure
      natriuresis relationship. A major objective of this brief review is to highlight
      some of the recent advances in our understanding of the mechanisms whereby the
      renal endothelin system, via endothelin type A- and endothelin type B-receptor
      activation, modulates renal pressure-natriuresis and blood pressure regulation
      under normal physiologic conditions and in certain forms of hypertension.

PMID- 16884662
TI  - Genetic information in the diagnosis and treatment of hypertension.
AB  - Advancement in cardiovascular science should be measured by a number of new
      diagnostic and therapeutic options applied in clinical practice as a result of
      translational research. Hypertension genetics is a good example of such a
      successful transfer of knowledge from bench to bedside. There are genetic methods
      currently used as diagnostic tools in patients presenting with secondary forms of
      hypertension, including primary hyperaldosteronism, Cushing's syndrome,
      pheochromocytoma, and chronic kidney disease. Directed treatment that corrects
      pathophysiologic abnormalities is available for several monogenic forms of
      hypertension as a result of uncovering their underlying genetic mechanisms.
      Progress in hypertension pharmacogenetics and pharmacogenomics brings closer a
      perspective of personalized antihypertensive treatment and gene transfer
      strategies, which, although still considered as innovative approaches, may soon
      become options to treat, control, and, possibly, cure hypertension.

PMID- 16884663
TI  - Secondary prevention of stroke by blood pressure-lowering treatment.
AB  - High blood pressure is the most important modifiable risk factor for stroke,
      accounting for more than 50% of the population-attributable fraction for stroke.
      There is now strong evidence from randomized trials that blood pressure-lowering
      treatment is one of the most effective and generalizable strategies for secondary
      prevention of stroke. Once the patient with stroke has stabilized, all patients
      should receive blood pressure-lowering therapy, irrespective of their blood
      pressure levels. Combination therapy with an angiotensin-converting enzyme (ACE)
      inhibitor plus a diuretic is an established regimen, but an angiotensin II
      receptor blocker may provide an alternative regimen in patients who do not
      tolerate an ACE inhibitor, especially in combination with a diuretic. For
      patients with previous stroke, goal blood pressures of < 130/80 mm Hg in
      hypertensive subjects and < 120/80 mm Hg in normotensive (or "prehypertensive")
      subjects should be achieved using combination blood pressure-lowering therapy.

PMID- 16884664
TI  - Moving beyond guidelines: are report cards the answer to high rates of
      uncontrolled hypertension?
AB  - Hypertension control rates remain alarmingly low worldwide despite the extensive
      evidence for decreased rates of cardiovascular, cerebrovascular, and renal events
      in response to blood pressure (BP) lowering to recommended targets. Several
      classes of antihypertensive drugs are available, which in combination can produce
      major decreases in BP, with minimal side effects. Moreover, most patients only
      have mild hypertension and, in general, can be controlled to < 140/90 mm Hg by
      proper combinations of two antihypertensive drugs. Although patient-related
      factors clearly contribute to poor control of hypertension, physician-related
      factors, particularly "passive" therapeutic inertia, are as responsible if not
      more so. Recent studies clearly indicate that monitoring performance of
      individual physicians and providing feedback on the care delivered by them can
      move treatment of hypertension to BP control rates in the 60% to 70% range. If
      health care organizations would implement this approach, enormous benefits could
      be expected for the prevention of cardiovascular and cerebrovascular disease.

PMID- 16884666
TI  - Alcohol and its relationship to blood pressure.
AB  - Ethanol is a molecule of enduring research interest because its consumption has
      important social as well as medical implications. With excessive ethanol
      consumption, there is higher prevalence for hypertension, stroke, cardiomyopathy,
      and arrhythmias. A principal mechanism by which ethanol exerts these
      cardiovascular effects is through modulation of blood pressure. In this article,
      we focus on recent research that pursues information on the effects of alcohol on
      blood pressure in human subjects, regardless of whether they have hypertension or
      not. Known means by which alcohol exerts hemodynamic effects are briefly covered,
      and insights on novel biomediators, such as endothelin and gene-based mechanisms,
      are presented. Newer tools, such as the Alcohol Use Disorders Identification Test
      Consumption Questions (AUDIT-C) survey and carbohydrate-deficient transferrin
      (CDT) serum test, are also covered. Reducing excessive alcohol intake can produce
      a reduction in blood pressure of up to 4 mm Hg, on average, which could
      substantially affect the rates of stroke and ischemic heart disease.

PMID- 16884665
TI  - Guiding antihypertensive treatment decisions using ambulatory blood pressure
      monitoring.
AB  - Compared with isolated clinic measurements, ambulatory blood pressure monitoring
      (ABPM) provides an insight into blood pressure (BP) changes in everyday life and
      an estimate of the overall BP load exerted on the cardiovascular system over 24
      hours. Cross-sectional evidence suggests a direct and significant relationship
      between ambulatory BP and organ damage. There is also longitudinal evidence for a
      superior predictive value of 24-hour BP in relation to the risk for
      cardiovascular morbidity and mortality as opposed to clinic BP. The usefulness of
      ABPM in pharmacologic studies aimed at evaluating the 24-hour antihypertensive
      efficacy of different drugs and drug combinations is now acknowledged. Among the
      mathematical indices available to explore 24-hour BP coverage by treatment, the
      ABPM-derived smoothness index provides a superior measure of the homogeneity of
      BP control compared with trough:peak ratios. The main applications of clinical
      practice should be in identifying patients with isolated office hypertension and
      those who are nonresponders to treatment, in assessing coverage of the 24-hour BP
      profile in high-risk patients and in diagnosing suspected treatment-related
      hypotension.

PMID- 16884668
TI  - Trends in recommendations for myelosuppressive chemotherapy for the treatment of
      solid tumors.
AB  - Lung, breast, and colorectal cancers are the 3 most frequent causes of cancer
      related death in the United States. In the past 15 years, survival has increased
      dramatically for patients with these tumor types, partly because improved
      chemotherapy caused major changes in standard care. In addition, maintaining
      chemotherapy dose intensity has an established a positive effect on patient
      outcomes. However, delivering chemotherapy at full dose and on schedule is
      limited primarily by myelosuppression. To determine how expert opinion about
      preferred chemotherapy for lung, breast, and colorectal cancers has changed over
      the past decade, the National Comprehensive Cancer Network (NCCN) treatment
      guidelines from 1996, 2000 or 2001, and 2005 for each tumor type were compared.
      The myelosuppressive potentials of NCCN-recommended agents were assessed using
      data from their prescribing information. Many agents and combinations of agents
      recommended in the NCCN guidelines for treating lung, breast, and colorectal
      cancers are associated with myelosuppression. Several of these myelosuppressive
      regimens, which were previously recommended for treating advanced-stage or
      metastatic disease, are now preferred for early-stage disease, and neoadjuvant or
      adjuvant therapy is now recommended in more tumor types and stages than ever
      before. These findings indicate that the cytotoxic agents and regimens
      recommended today are associated with more myelosuppression than those preferred
      a decade ago and are more widely used in early-stage disease when survival
      benefits are possible. Because of this trend toward more intensive treatment of
      patients with cancer, proactive steps should be taken to minimize the risk for
      myelosuppression and its complications while optimizing the relative dose
      intensity.

PMID- 16884667
TI  - Phosphodiesterase-5 inhibitors and their hemodynamic effects.
AB  - Erectile dysfunction occurs commonly in untreated and treated hypertensive
      patients, impairing adherence to treatment and quality of life. Furthermore, it
      is a marker for enhanced risk for cardiovascular disease. Phosphodiesterase type
      5 (PDE5) inhibitors, sildenafil, vardenafil, and tadalafil, provide effective
      treatment of erectile dysfunction. They reduce blood pressure in healthy
      patients: sildenafil 100 mg, -3.7/-3.6 mm Hg; vardenafil 20 mg, -7.5/-8 mm Hg;
      and tadalafil 20 mg, -1.6/-0.8 mm Hg. Greater declines in blood pressure with a
      PDE5 inhibitor may be observed in treated and untreated hypertensive patients.
      The additive effect of PDE5 inhibitors with one or multiple antihypertensive
      drugs is modest. alpha(1)-Blockers, except tamsulosin, may result in larger
      declines in blood pressure and cause orthostatic hypotension. Thus, caution
      should be exercised by using the lowest doses of proportional, variant(1)
      blockers and PDE5 inhibitors in combination. Nitrates in combination with PDE5
      inhibitors cause a profound decline in blood pressure and are contraindicated.

PMID- 16884669
TI  - Melanoma.

PMID- 16884671
TI  - Role of dermatologists in treating melanoma.
AB  - Melanoma is a major focus of dermatology training and practice, with
      dermatologists playing a central role in managing melanoma through primary
      prevention, secondary prevention, diagnosis, and treatment of thinner tumors.
      Dermatologists have led public health efforts to raise melanoma awareness,
      promulgate the early warning signs of melanoma, and promote melanoma prevention
      through sun protection. Dermatologists have unique expertise in melanoma risk
      assessment and the clinical diagnosis of melanoma through visual inspection and
      the use of diagnostic aids, including dermoscopy and photographically assisted
      follow-up. Increasing incidence of melanoma, earlier melanoma detection, narrower
      excision margins, and improved surgical training in dermatology have recently
      combined to enhance the role of dermatologists in melanoma care. For patients
      with thin primary melanomas, dermatologists are increasingly assuming complete
      care, including wide local excision and long-term surveillance for both disease
      recurrence and detection of new primary melanoma. Conversely, the advent of
      sentinel lymph node biopsy and adjuvant therapy has made melanoma management more
      complex and has intensified the need for a multidisciplinary approach to the
      disease. In this context, dermatologists contribute significantly to the
      formation, administration, and implementation of multidisciplinary melanoma
      programs.

PMID- 16884670
TI  - Update on immunotherapy for melanoma.
AB  - Several experimental immunotherapy approaches and standard therapy with high
      doses of interleukin (IL)-2 can cause prolonged objective responses in some
      patients with metastatic melanoma. Experimental immunotherapy approaches in
      clinical development include 1) cytokines such as IL-7 and IL-21, 2) cytokine
      antibody fusion proteins or immunocytokines, 3) whole tumor cell vaccines, 4)
      genetically modified tumor cells, 5) heat shock protein vaccines, 6) peptide
      vaccines, 7) dendritic cells pulsed with tumor antigens, 8) tumor antigen-naked
      DNA vectors, 9) recombinant viral vectors (either alone or in a prime boost
      schedule), 10) adoptive transfer of cloned tumor antigen-specific T cells, 11)
      Toll-like receptor ligands, 12) antagonistic antibodies to the cytotoxic T
      lymphocyte antigen 4 (CTLA4, CD152), and 13) activating antibodies to CD40 and
      CD137 (41-BB). These improved approaches to induce cytotoxic T-cell responses to
      tumors are based on a more detailed understanding of the immune system activation
      and regulation. The higher response rates with modern immunotherapy approaches
      may allow exploration of the molecular mechanisms that make tumor targets
      sensitive or resistant to immunotherapy.

PMID- 16884672
TI  - Merkel cell carcinoma.

PMID- 16884673
TI  - Role of radiotherapy in the management of merkel cell carcinoma of the skin.
AB  - The role of radiotherapy in treating local and regional disease in patients with
      clinically localized Merkel cell carcinoma remains controversial. Given the lack
      of randomized evidence and patient and treatment heterogeneity in published
      retrospective series, sound clinical judgment is required to assess individual
      patient risk factors. Although many single-institution series have shown that
      adjuvant radiation to the primary tumor site decreases the risk for local and
      regional failure, evidence is emerging that there is a cohort of patients at
      relatively low risk for local recurrence after wide local excision alone. Node
      dissection, radiotherapy, and combined modality treatment may all play a role in
      managing occult or clinically evident nodal disease, depending on the anatomic
      location of draining lymphatics and the extent of microscopic or macroscopic
      disease. For select patients, primary radiotherapy is a reasonable option with a
      low risk for local or regional recurrence.

PMID- 16884674
TI  - Surface dilational rheology of mixed adsorption layers at liquid interfaces.
AB  - The dilational rheology for mixed solutions of surface active compounds is easy
      to measure with existing methods, however, there are very few attempts only to
      analyse the resulting data on the basis of a theoretical model. Models by Jiang
      et al., Joos, and by Lucassen and van den Tempel (for single compounds) are
      compared here and applied to experimental data. The mentioned models converge to
      each other after some small modifications and represent a very good scientific
      background for studies of the mechanical behaviour of mixed adsorption layers. As
      example, the experimental results for mixed solutions containing a globular
      protein (beta-lactoglobulin) and a non-ionic surfactant (alkyl dimethyl phosphine
      oxide) are analysed by the obtained dependencies, using some new proposed
      numerical procedures.

PMID- 16884675
TI  - Polyethylenimine-based quality control assay for plasmid DNA.

PMID- 16884676
TI  - [Functional anatomy of the lymphatic drainage of the breast: contribution of
      sentinel lymph node biopsy].
AB  - OBJECTIVE: To make a development on the recent data of the literature concerning
      the functional anatomy of the lymphatic drainage of the breast, observed during
      interventions of sentinel lymph node biopsy; to compare the descriptive anatomy
      taking into consideration these new results. METHODS: The population of our
      descriptive anatomical study is made-up of five patients. All the patients
      underwent a radical mastectomy during which, an injection of 2 ml of patented
      blue, realized at the periareolar area allowed to observe the glandular lymphatic
      vessels. Bibliographic researches were undertaken on Internet site of the
      National Library of Medicine and on Internet site of the library of anatomy
      (Faculte de medecine des Saints-Peres Paris). RESULTS: Lymphatic anatomy of the
      breast was described since more than one century starting from works undertaken
      on anatomical subjects. Recent works, completed during sentinel lymph node
      biopsy, enriched these descriptive data of new functional anatomical data on the
      lymphatic drainage of the breast. Thus, the superficial ways of lymphatic
      drainage already described by Sappey, drain the surface glandular parenchyma
      until in the axillary lymph node. A deep plexux described more recently by Hidden
      drain the deep glandular parenchyma until in the internal mammary lymph nodes and
      the axillary lymph nodes. The results of our in vivo study corroborated the
      descriptive and functional data ever known. CONCLUSION: Thanks to the sentinel
      lymph node biopsy technique, the descriptive anatomy described since 1885, grows
      rich by new functional data which make it possible on the one hand, to understand
      at best the descriptive anatomy, and on the other hand, to apprehend the
      lymphonodal metastatic risk in breast cancer. These recent data are of an
      interest real, as well anatomical as therapeutic, and constitute a interesting
      research orientation.

PMID- 16884677
TI  - Streptomyces coelicolor oxidase (SCO2837p): a new free radical metalloenzyme
      secreted by Streptomyces coelicolor A3(2).
AB  - The SCO2837 open-reading frame is located within the conserved central core
      region of the Streptomyces coelicolor A3(2) genome, which contains genes required
      for essential cellular functions. SCO2837 protein (SCO2837p) expressed by Pichia
      pastoris is a copper metalloenzyme, catalyzing the oxidation of simple alcohols
      to aldehydes and reduction of dioxygen to hydrogen peroxide. Distinct optical
      absorption spectra are observed for oxidized and one-electron reduced holoenzyme,
      and a free radical EPR signal is present in the oxidized apoprotein,
      characteristic of the Tyr-Cys redox cofactor previously reported for fungal
      secretory radical copper oxidases, galactose oxidase and glyoxal oxidase, with
      which it shares weak sequence similarity. SCO2837p was detected in the growth
      medium of both S. coelicolor and a recombinant expression host (Streptomyces
      lividans TK64) by Western blotting, with the expression level dependent on the
      nature of the carbon source. This represents the first characterized example of a
      prokaryotic radical copper oxidase.

PMID- 16884678
TI  - Functional reconstitution of purified chloroquine resistance membrane transporter
      expressed in yeast.
AB  - Malaria is one of the major parasitic diseases. Current treatment of malaria is
      seriously hampered by the emergence of drug resistant cases. A once-effective
      drug chloroquine (CQ) has been rendered almost useless. The mechanism of CQ
      resistance is complicated and largely unknown. Recently, a novel transmembrane
      protein, Plasmodium falciparum chloroquine resistance transporter (PfCRT), has
      fulfilled all the requirements of being the CQ resistance gene. In order to
      elucidate the mechanism how PfCRT mediates CQ resistance, we have cloned the cDNA
      from a CQ sensitive parasite (3D7) and tried to express it in Pichia pastoris (P.
      pastoris) but with unsuccessful results due to AT-rich sequences in the malaria
      genome. We have therefore, based on the codon usage in P. pastoris, chemically
      synthesized a codon-modified pfcrt with an overall 55% AT content. This codon
      modified pfcrt has now been successfully expressed in P. pastoris. The expressed
      PfCRT has been purified with immuno metal affinity chromatography (IMAC) and then
      reconstituted into proteoliposome. It was found that proteoliposomes have a
      saturable, concentration and time-dependent CQ transport activity. In addition,
      we found that proteoliposomes with resistant PfCRT(r) (K76T or K76I) showed an
      increased CQ transport activity compared to liposomes with lipid alone, or
      proteoliposomes reconstituted with sensitive PfCRT(s) (K76) protein. This
      activity could be inhibited by nigericin and decreased with the removal of Cl(-).
      This work suggests that PfCRT is mediating CQR in P. falciparum by virtue of its
      changes in CQ transport activity depending on pH gradient and chloride ion in the
      food vacuole.

PMID- 16884679
TI  - Localization of telokin at the intercalated discs of cardiac myocytes.
AB  - Telokin is identical in sequence to the C-terminal portion of myosin light chain
      kinase but is expressed independently. We have used monoclonal antibodies
      specific to the non-telokin portion of myosin light chain kinase and to telokin,
      immunofluorescence microscopy and image reconstruction to demonstrate the
      presence of telokin in cardiac myocytes and to study its subcellular
      distribution. Antibodies to telokin labeled the intercalated discs of adult
      cardiac myocytes and similar structures in isolated intercalated disc
      preparations. Antibodies specific to the non-telokin portion of myosin light
      chain kinase did not label intercalated discs in either of these preparations.
      Western blots of isolated intercalated discs with anti-telokin revealed a 23kDa
      protein that co-migrates with purified telokin on SDS-PAGE. Deconvolution,
      reconstruction and analysis of fluorescence images of isolated intercalated discs
      labeled with anti-telokin and anti-beta-catenin, anti-gamma-catenin or anti
      connexin43 indicated that telokin is only partially co-localized with these
      proteins at the discs.

PMID- 16884680
TI  - Characterization in relation to development of an ecdysteroid agonist-responsive
      cytochrome P450, CYP18A1, in Lepidoptera.
AB  - Cytochrome P450 enzymes are involved in a number of steps in ecdysteroid
      (moulting hormone) homeostasis in insects. We report the cloning and
      characterization of an ecdysteroid agonist-responsive cytochrome P450, CYP18A1,
      from the cotton leafworm, Spodoptera littoralis. Northern blot analysis showed
      that the mRNA transcript was expressed at times of increasing ecdysteroid titre
      in final instar S. littoralis larvae and was induced by the ecdysteroid receptor
      agonist, RH-5992, in midgut and fat body. In addition, transcript expression was
      also detected in the prothoracic glands, a major ecdysteroid biosynthetic tissue,
      in both S. littoralis and the tobacco hornworm, Manduca sexta, at a time of
      increasing ecdysteroid titre. The exact significance of the temporal and spatial
      expression of CYP18A1 is unclear. The characterization of a P450 that is
      ecdysteroid agonist-responsive may provide a future target for exploitation in
      the development of novel insect control strategies.

PMID- 16884681
TI  - Multiple isoforms of myosin light chain 1 in pig diaphragm slow fibers:
      correlation with maximal shortening velocity and force generation.
AB  - Pig diaphragm slow fibers exhibit heterogeneity in myosin light chain 1 (MLC1)
      isoform expression, with many expressing fast-type MLC1 (MLC1F), as well as two
      isoforms of slow-type MLC1 (MLC1Sa and MLC1Sb). The goal of this study was to
      test if there is a relationship between MLC1 isoform expression and contractile
      properties among these fibers. Maximal shortening velocity (V(max)) and maximal
      isometric force generation, normalized with fiber cross-sectional area
      (P(o)/CSA), were measured in single fibers. V(max) was inversely related to the
      relative level of MLC1Sa. The level of MLC1Sa was reciprocally related to the
      levels of MLC1Sb and of MLC1F among individual fibers. Fibers expressing MLC1Sa
      and in which MLC1Sb was not detected generated greater P(o)/CSA, compared to
      fibers expressing MLC1Sb and not MLC1Sa. The results indicate a complex pattern
      of MLC1 isoform expression among pig diaphragm slow fibers and suggest that
      shortening velocity and force generation are modulated, in these fibers, by the
      MLC1 isoform composition.

PMID- 16884682
TI  - Novel allosteric properties produced by residue substitutions in the subunit
      interface of yeast NAD+-specific isocitrate dehydrogenase.
AB  - Yeast NAD+-specific isocitrate dehydrogenase (IDH) is an octamer of four IDH1 and
      four IDH2 subunits, and the basic structural unit of the enzyme is an IDH1/IDH2
      heterodimer. To investigate one aspect of the interaction between IDH1 and IDH2,
      residues in a hydrophobic region at the heterodimer interface (Val-216, Ser-220,
      and Val-224 in IDH1; Ile-221, Val-225, and Val-229 in IDH2) were replaced by
      alanine residues in each and in both subunits. Gel filtration and sedimentation
      velocity analyses demonstrated that the residue substitutions do not disrupt the
      octameric structure of IDH. However, these substitutions produce novel kinetic
      properties including, with respect to cofactor, positive allosteric regulation by
      AMP and cooperativity in the absence of AMP. These allosteric properties are also
      apparent in NAD+-binding experiments. Despite substantial measurable activity for
      the mutant enzyme containing residue substitutions in both subunits, expression
      of this enzyme produces growth phenotypes indicative of IDH dysfunction in vivo.

PMID- 16884683
TI  - Interactions of bovine lactoferricin with acidic phospholipid bilayers and its
      antimicrobial activity as studied by solid-state NMR.
AB  - Bovine lactoferricin (LfcinB) is an antimicrobial peptide released by pepsin
      cleavage of lactoferrin. In this work, the interaction between LfcinB and acidic
      phospholipid bilayers with the weight percentage of 65%
      dimyristoylphosphatidylglycerol (DMPG), 10% cardiolipin (CL) and 25%
      dimyristoylphosphatidylcholine (DMPC) was investigated as a mimic of cell
      membrane of Staphylococcus aureus by means of quartz crystal microbalance (QCM)
      and solid-state (31)P and (1)H NMR spectroscopy. Moreover, we elucidated a
      molecular mechanism of the antimicrobial activity of LfcinB by means of potassium
      ion selective electrode (ISE). It turned out that affinity of LfcinB for acidic
      phospholipid bilayers was higher than that for neutral phospholipid bilayers. It
      was also revealed that the association constant of LfcinB was larger than that of
      lactoferrin as a result of QCM measurements. (31)P DD-static NMR spectra
      indicated that LfcinB interacted with acidic phospholipid bilayers and bilayer
      defects were observed in the bilayer systems because isotropic peaks were clearly
      appeared. Gel-to-liquid crystalline phase transition temperatures (Tc) in the
      mixed bilayer systems were determined by measuring the temperature variation of
      relative intensities of acyl chains in (1)H MAS NMR spectra. Tc values of the
      acidic phospholipid and LfcinB-acidic phospholipid bilayer systems were 21.5
      degrees C and 24.0 degrees C, respectively. To characterize the bilayer defects,
      potassium ion permeation across the membrane was observed by ISE measurements.
      The experimental results suggest that LfcinB caused pores in the acidic
      phospholipid bilayers. Because these pores lead the permeability across the
      membrane, the molecular mechanism of the antimicrobial activity could be
      attributed to the pore formation in the bacterial membrane induced by LfcinB.

PMID- 16884684
TI  - Purification and characterization of two protein kinases acting on the aquaporin
      SoPIP2;1.
AB  - Aquaporins are water channel proteins that facilitate the movement of water and
      other small solutes across biological membranes. Plants usually have large
      aquaporin families, providing them with many ways to regulate the water
      transport. Some aquaporins are regulated post-translationally by phosphorylation.
      We have previously shown that the water channel activity of SoPIP2;1, an
      aquaporin in the plasma membrane of spinach leaves, was enhanced by
      phosphorylation at Ser115 and Ser274. These two serine residues are highly
      conserved in all plasma membrane aquaporins of the PIP2 subgroup. In this study
      we have purified and characterized two protein kinases phosphorylating Ser115 and
      Ser274 in SoPIP2;1. By anion exchange chromatography, the Ser115 kinase was
      purified from the soluble protein fraction isolated from spinach leaves. The Ca2+
      dependent Ser274 kinase was purified by peptide affinity chromatography using
      plasma membranes isolated from spinach leaves. When characterized, the Ser115
      kinase was Mg2+-dependent, Ca2+-independent and had a pH-optimum at 6.5. In
      accordance with previous studies using the oocyte expression system, site
      directed mutagenesis and kinase and phosphatase inhibitors, the phosphorylation
      of Ser274, but not of Ser115, was increased in the presence of phosphatase
      inhibitors while kinase inhibitors decreased the phosphorylation of both Ser274
      and Ser115. The molecular weight of the Ser274 kinase was approximately 50 kDa.
      The identification and characterization of these two protein kinases is an
      important step towards elucidating the signal transduction pathway for gating of
      the aquaporin SoPIP2;1.

PMID- 16884686
TI  - Identification and Herc5-mediated ISGylation of novel target proteins.
AB  - ISG15, a protein containing two ubiquitin-like domains, is an interferon
      stimulated gene product that functions in antiviral response and is conjugated to
      various cellular proteins (ISGylation) upon interferon stimulation. ISGylation
      occurs via a pathway similar to the pathway for ubiquitination that requires the
      sequential action of E1/E2/E3: the E1 (UBE1L), E2 (UbcH8), and E3 (Efp/Herc5)
      enzymes for ISGylation have been hitherto identified. In this study, we
      identified six novel candidate target proteins for ISGylation by a proteomic
      approach. Four candidate target proteins were demonstrated to be ISGylated in
      UBE1L- and UbcH8-dependent manners, and ISGylation of the respective target
      proteins was stimulated by Herc5. In addition, Herc5 was capable of binding with
      the respective target proteins. Thus, these results suggest that Herc5 functions
      as a general E3 ligase for protein ISGylation.

PMID- 16884685
TI  - The C-type Arabidopsis thioredoxin reductase ANTR-C acts as an electron donor to
      2-Cys peroxiredoxins in chloroplasts.
AB  - 2-Cys peroxiredoxins (Prxs) play important roles in the antioxidative defense
      systems of plant chloroplasts. In order to determine the interaction partner for
      these proteins in Arabidopsis, we used a yeast two-hybrid screening procedure
      with a C175S-mutant of Arabidopsis 2-Cys Prx-A as bait. A cDNA encoding an NADPH
      dependent thioredoxin reductase (NTR) isotype C was identified and designated
      ANTR-C. We demonstrated that this protein effected efficient transfer of
      electrons from NADPH to the 2-Cys Prxs of chloroplasts. Interaction between 2-Cys
      Prx-A and ANTR-C was confirmed by a pull-down experiment. ANTR-C contained N
      terminal TR and C-terminal Trx domains. It exhibited both TR and Trx activities
      and co-localized with 2-Cys Prx-A in chloroplasts. These results suggest that
      ANTR-C functions as an electron donor for plastidial 2-Cys Prxs and represents
      the NADPH-dependent TR/Trx system in chloroplasts.

PMID- 16884687
TI  - BRAK/CXCL14 expression suppresses tumor growth in vivo in human oral carcinoma
      cells.
AB  - In order to find a suppressor(s) of tumor progression in vivo for oral carcinoma
      (OC), we searched for molecules down-regulated in OC cells when the cells were
      treated with epidermal growth factor (EGF), whose receptor is frequently over
      activated in OC. The expression of BRAK, which is also known as CXC chemokine
      ligand14 (CXCL14), was down-regulated significantly by the treatment of OC cells
      with EGF as observed by cDNA microarray analysis followed by reverse
      transcriptase polymerase chain reaction analysis. The EGF effect was attenuated
      by the co-presence of a MEK inhibitor. The rate of tumor formation in vivo of
      BRAK-expressing vector-transfected tumor cells in athymic nude mice was
      significantly lower than that of mock vector-transfected ones. In addition tumors
      formed in vivo by the BRAK-expressing cells were significantly smaller than those
      of the mock-transfected ones. These results indicate that BRAK/CXCL14 is a
      chemokine, having suppressive activity toward tumor progression of OC in vivo.

PMID- 16884688
TI  - Mutations within the human GLYT2 (SLC6A5) gene associated with hyperekplexia.
AB  - Hereditary hyperekplexia is a neuromotor disorder characterized by exaggerated
      startle reflexes and muscle stiffness in the neonate. The disease has been
      associated with mutations in the glycine receptor subunit genes GLRA1 and GLRB.
      Here, we describe mutations within the neuronal glycine transporter 2 gene
      (GLYT2, or SLC6A5, ) of hyperekplexia patients, whose symptoms cannot be
      attributed to glycine receptor mutations. One of the GLYT2 mutations identified
      causes truncation of the transporter protein and a complete loss of transport
      function. Our results are consistent with GLYT2 being a disease gene in human
      hyperekplexia.

PMID- 16884689
TI  - siRNA-mediated depletion of endogenous protein phosphatase 2Acalpha markedly
      attenuates ceramide-activated protein phosphatase activity in insulin-secreting
      INS-832/13 cells.
AB  - The sphingolipid ceramide (CER) and its metabolites have been recognized as
      important mediators of signal transduction processes leading to a variety of
      cellular responses, including survival and demise via apoptosis. Accumulating
      evidence implicates key regulatory roles for intracellularly generated CER in
      metabolic dysfunction of the islet beta cell. We have previously reported
      localization of an okadaic (OKA)-sensitive CER-activated protein phosphatase
      (CAPP) in the islet beta cell. We have also reported immunological identification
      of the structural A subunit, the regulatory B56alpha subunit, and the catalytic C
      subunit for CAPP holoenzyme complex in insulin-secreting INS-1 cells. Herein, we
      provide the first evidence to suggest that siRNA-mediated knockdown of the alpha
      isoform of the catalytic subunit of PP2Ac (PP2Acalpha) markedly reduces the CAPP
      activity in INS 832/13 cells. Potential significance of the functional activation
      of CAPP holoenzyme in the context of lipid-and glucose-induced metabolic
      dysfunction of the islet beta cell is discussed.

PMID- 16884690
TI  - Copper-dependent interaction of glutaredoxin with the N termini of the copper
      ATPases (ATP7A and ATP7B) defective in Menkes and Wilson diseases.
AB  - The P-type ATPases affected in Menkes and Wilson diseases, ATP7A and ATP7B,
      respectively, are key copper transporters that regulate copper homeostasis. The N
      termini of these proteins are critical in regulating their function and activity,
      and contain six copper-binding motifs MxCxxC. In this study, we describe the
      identification of glutaredoxin (GRX1) as an interacting partner of both ATP7A and
      ATP7B, confirmed by yeast two-hybrid technology and by co-immunoprecipitation
      from mammalian cells. The interaction required the presence of copper and intact
      metal-binding motifs. In addition, the interaction was related to the number of
      metal-binding domains available. GRX1 catalyses the reduction of disulphide
      bridges and reverses the glutathionylation of proteins to regulate and/or protect
      protein activity. We propose that GRX1 is essential for ATPase function and
      catalyses either the reduction of intramolecular disulphide bonds or the
      deglutathionylation of the cysteine residues within the CxxC motifs to facilitate
      copper-binding for subsequent transport.

PMID- 16884691
TI  - A novel type of EWS-CHOP fusion gene in myxoid liposarcoma.
AB  - The cytogenetic hallmark of myxoid type and round cell type liposarcoma consists
      of reciprocal translocation of t(12;16)(q13;p11) and t(12;22)(q13;q12), which
      results in fusion of TLS/FUS and CHOP, and EWS and CHOP, respectively. Nine
      structural variations of the TLS/FUS-CHOP chimeric transcript have been reported,
      however, only two types of EWS-CHOP have been described. We describe here a case
      of myxoid liposarcoma containing a novel EWS-CHOP chimeric transcript and
      identified the breakpoint occurring in intron 13 of EWS. Reverse transcription
      polymerase chain reaction and direct sequence showed that exon 13 of EWS was in
      frame fused to exon 2 of CHOP. Genomic analysis revealed that the breaks were
      located in intron 13 of EWS and intron 1 of CHOP.

PMID- 16884692
TI  - 15-Deoxyspergualin modulates Plasmodium falciparum heat shock protein function.
AB  - Heat shock proteins are essential for the survival of all cells. The C-terminal
      EEVD motif of Hsp70 has previously been implicated in binding 15-deoxyspergualin
      (DSG), an immunosuppressant with antimalarial activity whose mechanism of action
      is uncertain. We report the cloning, overexpression, and characterization of
      three members of the heat shock family, PfHsp70-1 (an Hsp70 protein with a C
      terminal EEVD motif), PfHsp70-2 (an Hsp70 protein without the EEVD motif), and
      PfHsp70 interacting protein. The chaperone activity of PfHsp70-1, and PfHsp70-2
      was enhanced by ATP and by PfHip. Interestingly, while binding of protein
      substrates to PfHsp70-1, PfHsp70-2 and PfHip was unaffected in the presence of
      DSG, the ATP enhanced chaperone activity of PfHsp70-1 but not PfHsp70-2 was
      stimulated further by DSG. Our finding suggests that the binding partner of DSG
      in the parasite cellular milieu is PfHsp70-1 and paves the way for the
      elucidation of the mechanism of antimalarial action of DSG.

PMID- 16884693
TI  - Antioxidant effect of bisphosphonates and simvastatin on chondrocyte lipid
      peroxidation.
AB  - The objective of this study was to evaluate the effect of bisphosphonates (BPs)
      and simvastatin on chondrocyte lipid peroxidation. For this purpose, a flow
      cytometrical method using C11-BODIPY(581/591) was developed to detect
      hydroperoxide-induced lipid peroxidation in chondrocytes. Tertiary
      butylhydroperoxide (t-BHP) induced a time and concentration dependent increase in
      chondrocyte lipid peroxidation. Addition of a Fe2+/EDTA complex to t-BHP or
      hydrogen peroxide (H2O2) clearly enhanced lipid peroxidation. The lipophilic
      simvastatin demonstrated a small inhibition in the chondrocyte lipid
      peroxidation. None of three tested BPs (clodronate, pamidronate, and risedronate)
      had an effect on chondrocyte lipid peroxidation induced by t-BHP. However, when
      Fe2+/EDTA complex was added to t-BHP or H2O2, BPs inhibited the lipid
      peroxidation process varying from 25% to 58%. This study demonstrates that BPs
      have antioxidant properties as iron chelators, thereby inhibiting the chondrocyte
      lipid peroxidation. These findings add evidence to the therapeutic potential of
      bisphosphonates and statins in rheumatoid arthritis.

PMID- 16884694
TI  - Listeria monocytogenes induced Rac1-dependent signal transduction in endothelial
      cells.
AB  - Infection of endothelial cells by Listeria monocytogenes is an essential step in
      the pathogenesis of listeriosis. Small GTPases of the Rho family act as molecular
      switches in signal transduction. We tested the hypothesis that Rho GTPases
      contribute to the regulation of cytokine expression following L. monocytogenes
      infection. L. monocytogenes induced release of distinct CC and CXC, as well as
      Th1 and Th2 cytokines and growth factors by endothelial cells and activated RhoA
      and Rac1. Inhibition of Rac1 by inhibitor Nsc23766 reduced cytokine expression,
      and slightly yet significantly the uptake of bacteria. Blocking of Rho proteins
      by Clostridium difficile toxin B-10463 (TcdB) reduced Listeria-dependent cytokine
      expression, whereas activating Rho proteins by Escherichia coli CNF1 increased
      it. We analyzed regulation of IL-8 expression in more detail: Listeria-induced IL
      8 release was reduced by inhibition of RhoA, Rac1 and Cdc42 (TcdB) or Rac1 while
      blocking of RhoA/B/C by Clostridium limosum C3 fusion toxin (C3FT) or Rho kinase
      by Y27632 reduced cytokine expression only slightly. Activation of RhoA, Rac1 and
      Cdc42 (CNF1), but not of RhoA alone (CNF(Y)), enhanced Listeria-dependent IL-8
      release significantly. Furthermore, inhibition of RhoA, Rac1 and Cdc42 (TcdB) and
      Rac1 (Nsc23766), but not of RhoA (C3FT) reduced Listeria-related recruitment of
      NF-kappaB/p65 and RNA polymerase II to the il8 promoter, as well as acetylation
      of histone H4 and Ser10/Lys14-phosphorylation/acetylation of histone H3 at the
      il8 gene promoter in HUVEC. In conclusion, Rac1 contributed to L. monocytogenes
      induced cytokine expression by human endothelial cells.

PMID- 16884695
TI  - Multiple role of histamine H1-receptor-PKC-MAPK signalling pathway in histamine
      stimulated nerve growth factor synthesis and secretion.
AB  - Histamine is a potent stimulator of nerve growth factor (NGF) production in the
      central nerve system and in the periphery as well. In this review, the
      biochemical mechanisms of histamine-stimulated NGF synthesis and secretion, and
      interactions between histamine, interleukin-1beta, and interleukin-6 are
      discussed. The main signalling pathway, involved in the stimulation of NGF
      production by histamine, includes activation of histamine H(1)-receptor,
      stimulation of Ca(2+)-dependent protein kinase C and mitogen-activated protein
      kinase. The same signalling pathway is involved in the interactions between
      histamine, interleukin-1beta, and interleukin-6, where NGF secretion is
      amplified. Whereas histamine and interleukin-1beta cause additive stimulatory
      effect on NGF secretion, interaction between histamine and interleukin-6 causes a
      long-term synergism. Thus, activation of histamine H(1)-receptor-protein kinase C
      mitogen-activated protein kinase signalling pathway plays a crucial role not only
      in the direct stimulation of NGF secretion by histamine, but also in the indirect
      stimulation via different types of interactions between histamine, interleukin
      1beta, and interleukin-6, which may have important therapeutic implications in
      modulation of NGF production.

PMID- 16884697
TI  - A genetic study of the suppressors of the Engrailed-1 cerebellar phenotype.
AB  - The mouse Engrailed genes, En1 and En2, play an important role in the development
      of the cerebellum from its inception at the mid/hindbrain boundary in early
      embryonic development through cell type specification events and beyond. In the
      absence of En1, the cerebellum and caudal midbrain fail to develop normally--a
      phenotype that we have previously reported to be strain dependent. On the 129/S1
      strain background, En1 null alleles lead to mid/hindbrain failure, whereas on the
      C57BL/6 background, En1 deficiency is compatible with near normal cerebellar
      development. We have pursued this dramatic effect of genetic background by
      performing a genetic modifier screen through F1 backcross and F1 intercross
      matings. The backcross has yielded two strong candidate intervals with suggestive
      linkage to a third region. Moreover, variations in rescue frequency among
      subgroups within the backcross indicate gender and parent of origin influences on
      rescue penetrance. The intercross data reveal locus heterogeneity of the En1
      modifiers, with more than one compliment of C57BL/6 and 129/S1 alleles capable of
      mediating the rescue phenotype. These findings highlight the complexity and
      plasticity of gene networks involved in brain development.

PMID- 16884696
TI  - Nicotine-induced changes of glutamate and arginine in naive and chronically
      alcoholized rats: an in vivo microdialysis study.
AB  - The effects of nicotine, when administered either acutely or chronically, at
      doses of 0.15, 0.3 or 0.6 mg/kg, on the release of glutamate and arginine in the
      rat nucleus accumbens have been studied in microdialysis experiments. Glutamate
      release significantly increased after acute nicotine injection, 0.3 mg/kg, which
      was accentuated if there was a priming regime of saline for the previous 27 days.
      This is possibly related to the rewarding effects of nicotine. Five hours after
      cessation of chronic oral nicotine administration, there were significant
      increases in glutamate content, which was possibly reflective of a withdrawal
      process. Significant decreases in nucleus accumbens arginine release were
      evident, between 1 and 2 h, after chronic nicotine administration. When nicotine
      was co-administered to rats during chronic ethanol intoxication, at either 0.15
      mg/kg or 0.3 mg/kg doses, glutamate release did not increase during the first 12
      h of withdrawal. However, a decrease in arginine microdialysate content was still
      observed with all nicotine doses. The nicotine-induced changes in glutamate and
      arginine release in nucleus accumbens highlights the complex neuropharmacological
      interactions evoked by this compound and also identified its possible modulating
      effect on glutamate release during the initial stages of chronic ethanol
      withdrawal.

PMID- 16884698
TI  - Blood-brain barrier targeting of BDNF improves motor function in rats with middle
      cerebral artery occlusion.
AB  - Intravenous brain-derived neurotrophic factor (BDNF) causes a 65-70% reduction in
      stroke volume in rats with the middle cerebral artery occlusion (MCAO), provided
      the BDNF is conjugated to a blood-brain barrier (BBB) molecular Trojan horse. The
      latter may be a peptidomimetic monoclonal antibody (MAb) to the transferrin
      receptor. The present studies determine whether the effects on stroke volume
      correlate with an improvement in neuro-behavior using the rotarod test. The
      rotarod latency was >200 s at 16 RPM in all rats pre-MCAO. The latency was 30+/-7
      s and 103+/-9 s at 24 h post-MCAO in the animals treated with BDNF alone and the
      BDNF-MAb conjugate, respectively. These studies show that when BDNF is formulated
      to enable transport across the BBB, the intravenous administration of the
      neurotrophin results in a reduction in stroke volume that is associated with a
      parallel improvement in functional outcome.

PMID- 16884699
TI  - Adenoviral gene transfer of hepatocyte growth factor prevents death of injured
      adult motoneurons after peripheral nerve avulsion.
AB  - Hepatocyte growth factor (HGF) exhibits strong neurotrophic activities on
      motoneurons both in vitro and in vivo. We examined survival-promoting effects of
      an adenoviral vector encoding human HGF (AxCAhHGF) on injured adult rat
      motoneurons after peripheral nerve avulsion. The production of HGF in COS1 cells
      infected with AxCAhHGF and its bioactivity were confirmed by ELISA, Western blot
      and Madin-Darby canine kidney (MDCK) cell scatter assay. The facial nerve or the
      seventh cervical segment (C7) ventral and dorsal roots of 3-month-old Fischer 344
      male rats were then avulsed and removed from the stylomastoid or vertebral
      foramen, respectively, and AxCAhHGF, AxCALacZ (adenovirus encoding beta
      galactosidase gene) or phosphate-buffered saline (PBS) was inoculated in the
      lesioned foramen. Treatment with AxCAhHGF after avulsion significantly prevented
      the loss of injured facial and C7 ventral motoneurons as compared to AxCALacZ or
      PBS treatment and ameliorated choline acetyltransferase immunoreactivity in these
      neurons. These results indicate that HGF may prevent the degeneration of
      motoneurons in adult humans with motoneuron injury and motor neuron diseases.

PMID- 16884700
TI  - Central glucagon like peptide-1 delays solid gastric emptying via central CRF and
      peripheral sympathetic pathway in rats.
AB  - It has been shown that glucagon like peptide-1 (GLP-1) acts on the central
      nervous system (CNS), in addition to its peripheral actions. Central
      administration of glucagon like peptide-1 (GLP-1) delays liquid gastric emptying
      via non-adrenergic, non-cholinergic neurons in rats. However, it remains unclear
      how central GLP-1 delays solid gastric emptying in rats. GLP-1 receptors at the
      CNS mediates the endocrine and anxiety responses to psychogenic and interoceptive
      stress. Corticotropin-releasing factor (CRF) is also known as a stress-related
      peptide, which delays gastric emptying of liquid and solid food via the autonomic
      nervous system. We have recently showed that central CRF delays solid gastric
      emptying via sympathetic pathways in rats. However, it remains unknown how
      central GLP-1 and CRF interact in mediating the inhibitory effect on solid
      gastric emptying. After a 24 h-fasting, GLP-1 was administered by intracisternal
      (ic)-injection immediately after the solid meal ingestion. Ninety minutes after
      the peptide injection, gastric contents were measured. Ic-injection of GLP-1 (30
      3000 pmol) dose-dependently inhibited solid gastric emptying. Ic-injection of GLP
      1 (3000 pmol)-induced delay of gastric emptying was partially antagonized by
      celiac ganglionectomy but not by atropine or N(G)-nitro-l-arginine methyl ester
      (L-NAME). Ic-injection of a CRF antagonist, astressin (2.8 nmol), partially
      antagonized GLP-1-induced delay of solid gastric emptying. These results indicate
      that central CRF and peripheral sympathetic pathway are, at least in part,
      involved in mediating central GLP-1-induced delay of solid gastric emptying in
      rats.

PMID- 16884701
TI  - Cell cycle deregulation and loss of stem cell phenotype in the subventricular
      zone of TGF-beta adaptor elf-/- mouse brain.
AB  - The mammalian forebrain subependyma contains neural stem cells and other
      proliferating progenitor cells. Recent studies have shown the importance of TGF
      beta family members and their adaptor proteins in the inhibition of proliferation
      in the nervous system. Previously, we have demonstrated that TGF-beta induces
      phosphorylation and association of ELF (embryonic liver fodrin) with Smad3 and
      Smad4 resulting in nuclear translocation. Elf(-/-) mice manifest abnormal
      neuronal differentiation, with loss of neuroepithelial progenitor cell phenotype
      in the subventricular zone (SVZ) with dramatic marginal cell hyperplasia and loss
      of nestin expression. Here, we have analyzed the expression of cell cycle
      associated proteins cdk4, mdm2, p21, and pRb family members in the brain of elf(
      /-) mice to verify the role of elf in the regulation of neural precursor cells in
      the mammalian brain. Increased proliferation in SVZ cells of the mutant mice
      coincided with higher levels of cdk4 and mdm2 expression. A lesser degree of
      apoptosis was observed in the mutant mice compared to the wild-type control. Elf(
      /-) embryos showed elevated levels of hyperphosphorylated forms of pRb, p130 and
      p107 and decreased level of p21 compared to the wild-type control. These results
      establish a critical role for elf in the development of a SVZ neuroepithelial
      stem cell phenotype and regulation of neuroepithelial cell proliferation,
      suggesting that a mutation in the elf locus renders the cells susceptible to a
      faster entry into S phase of cell cycle and resistance to senescence and
      apoptotic stimuli.

PMID- 16884704
TI  - Synthesis of a di- and a trisaccharide related to the O-antigen of Escherichia
      coli O83:K24:H31.
AB  - Di- and trisaccharide fragments related to the repeating unit of the O-antigen of
      Escherichia coli O83:K24:H31 have been synthesized as their methyl glycoside
      analogs starting from readily available monosaccharides.

PMID- 16884702
TI  - Tandospirone, a 5-HT1A agonist, ameliorates movement disorder via non
      dopaminergic systems in rats with unilateral 6-hydroxydopamine-generated lesions.
AB  - Serotonin 1A (5-HT1A) receptors are distributed throughout the brain with their
      highest concentrations in the frontal cortex, subthalamic nucleus and
      entopeduncular nucleus as well as the dorsal and median raphe nucleus. There is
      growing evidence that 5-HT1A receptor agonists have an antidepressant effect in
      individuals with major depressive disorders. Recent clinical studies suggest that
      tandospirone, a highly potent and selective 5-HT1A receptor agonist used
      clinically as an antidepressant in Japan and China, may act as an
      antiparkinsonian drug. In the present study, we investigated the effect of
      tandospirone on contralateral rotational behavior in a unilateral
      hemiparkinsonian rat model produced with 6-hydroxydopamine (6-OHDA).
      Tandospirone, as well as 8-hydroxy-2-(di-n-propylamino) tetralin (8-OHDPAT),
      significantly increased contralateral turnings in a dose-dependent manner (0.5-10
      mg/kg). Tandospirone also remarkably potentiated the contralateral turning
      induced by 0.025 mg/kg of apomorphine. Pretreatment with WAY-100635, a 5-HT1A
      receptor antagonist, almost completely blocked the contralateral turning behavior
      evoked by tandospirone and 8-OHDPAT, but not that by apomorphine. SCH-23390, a
      selective dopamine D1 receptor antagonist, did not affect on the tandospirone
      induced rotational behavior. These results suggested that tandospirone could act
      on postsynaptic 5-HT1A receptors and modulate excitatory amino acid pathways in
      the basal ganglia. Thus, tandospirone could have therapeutic potential for the
      treatment of Parkinson's disease by modulating neuronal activities of non
      dopaminergic pathways.

PMID- 16884703
TI  - Effect of N-acetylcysteine, allopurinol and vitamin E on jaundice-induced brain
      oxidative stress in rats.
AB  - We examined the possible protective effect of certain antioxidants (N
      acetylcysteine, allopurinol and vitamin E) against the oxidative stress of brain
      tissue induced by experimental obstructive jaundice in rats. Thirty-six male
      Wistar rats were randomly divided into six groups; group I control, group II sham
      operated, group III bile duct ligated and groups IV, V, and VI in which the rats,
      after bile duct ligation, were given every day an intraperitoneal injection with
      N-acetylcysteine, allopurinol and Vit-E respectively. All rats were sacrificed on
      the tenth day by exsanguination and the oxidative state in samples from cortex,
      midbrain and cerebellum was assessed by measuring the thiol redox state and lipid
      peroxidation quantified by MDA measurements. The main finding was that all three
      antioxidants decrease lipid peroxidation in the three brain areas. Cysteine
      levels increased and protein thiol levels were reserved only in the group treated
      with N-acetylcysteine, whereas oxidized glutathione increased dramatically in the
      group treated with allopurinol, suggesting that each antioxidant agent had a
      certain influence profile on the different antioxidant defense systems. The
      observed effects of the antioxidants in this experimental model could also
      provide insight into some aspects of jaundice-induced hepatic encephalopathy in
      humans.

PMID- 16884705
TI  - Structural characterisation of novel lichen heteroglycans by NMR spectroscopy and
      methylation analysis.
AB  - Two galactofuranomannans, Ths-4 and Ths-5, were isolated from the lichen,
      Thamnolia vermicularis var. subuliformis, using ethanol fractionation and anion
      exchange and size-exclusion chromatography. The average molecular weights of Ths
      4 and Ths-5 were estimated to be 19 and 200 kDa, respectively. Structural
      characterisation of Ths-4, Ths-5 and their partially hydrolysed derivatives was
      performed by methanolysis and methylation analysis. The intact and partially
      hydrolysed Ths-4 was further analysed using NMR spectroscopy (1D, COSY, NOESY,
      TOCSY, HSQC and HMBC). According to the data obtained, the heteroglycans Ths-4
      and Ths-5 have similar structures, but have large differences in molecular
      weight. The structure is composed of 3-O-linked and 5-O-linked galactofuranosyl
      chains linked to a mannan core. The mannan core consists of a main chain of alpha
      (1-->6)-linked mannopyranosyl residues, substituted at O-2 with either a single
      alpha-mannopyranosyl unit or an alpha-Manp-(1-->2)-alpha-Manp-(1-->2)-alpha-Manp
      group in the ratio of approximately 1:3, respectively. The polysaccharides have
      idealised repeating blocks as is shown.

PMID- 16884706
TI  - Hypoxia in lung vascular biology and disease.

PMID- 16884707
TI  - Major histocompatibility complex class I restricted T-cell autoreactivity in
      human peripheral blood mononuclear cells.
AB  - During selection in the thymus or any subsequent response, T-cells recognize
      peptides bound to major histocompatibility complex (MHC) molecules. Peptides
      produced by lysosomes or by proteasome/immunoproteasome stimulate CD4+ or CD8+ T
      cell, respectively. Inflammation alters components of both antigen-processing
      pathways resulting in the production of different peptides. The role of such
      changes in self/non-self discrimination was examined in autologous mixed
      peripheral blood mononuclear cell cultures. Stimulator cells were incubated in
      the presence or absence of INF-gamma, with or without lysosome inhibitors
      (ammonium chloride/chloroquine), cathepsin inhibitor (E-64), or
      proteasome/immunoproteasome inhibitor (epoxomicin). Responder cells were added
      and zeta-chain phosphorylated forms were used as read out. INF-gamma did not
      affect zeta-chain phosphorylated forms, which means that the expected INF-gamma
      induced alterations in antigen processing machinery do not influence self/non
      self discrimination. Surprisingly, the completely phosphorylated 23-kDa zeta
      chain was always present except in the case of epoxomicin, indicating the
      presence of MHC class I restricted autoreactive CD8+ T-cells but not of MHC class
      II restricted autoreactive CD4+ T-cells, possibly due to more efficient negative
      selection in the thymus of the latter. Autoimmunity is prevented due to absence
      of help by CD4+ T-cells. This conclusion was confirmed by the lack of differences
      in IL-2 levels in cell culture supernatants, as well as, by the absence of
      differences in cell proliferation under the various conditions described above.

PMID- 16884708
TI  - Mitochondrial P450s.
AB  - Cytochrome P450 was first found in the microsomes from animal tissues, and then
      the presence of P450 in mitochondria was reported for the steroidogenic organs,
      adrenal gland and gonads. Three forms of mitochondrial P450 (11A, 11B1, and 11B2)
      were purified from these organs and their functions in steroid hormone
      biosynthesis were confirmed. Later studies showed the presence of several other
      forms of P450 (24A, 27A, 27B, and 27C) in the mitochondria of various non
      steroidogenic organs including liver and kidney. These mitochondrial P450s were
      found to participate in the biosynthesis of bile acids from cholesterol in the
      liver, and the metabolic activation of Vitamin D3 to its active form, 1,25
      dihydroxyvitamin D3, in the liver and the kidney. In contrast to the "drug
      metabolizing" P450s in microsomes, most mitochondrial P450s show high specificity
      to their endogenous substrates, and have negligible activity towards xenobiotic
      compounds. In contrast to these established roles of mitochondrial P450s in the
      metabolism of endogenous substrates, the metabolism of xenobiotic chemicals by
      P450-catalyzed reactions in mitochondria has long been a subject of controversy.
      It is now known that all P450s in eukaryotic organisms are coded by nuclear
      genes, and the nascent peptides of various forms of P450 synthesized by
      cytoplasmic ribosomes are targeted to either endoplasmic reticulum (ER) or
      mitochondria depending on the ER-targeting sequence or the mitochondria-targeting
      sequence present in their amino-terminal portion. However, the presence of some
      microsome-type P450s in the mitochondria from various animal tissues including
      liver and brain has been reported. Possible mechanisms of intracellular sorting
      of some microsome-type P450s to mitochondria have been proposed, although
      physiological significance of the contribution of P450s in mitochondria to the
      metabolism of xenobiotic chemicals in animal tissues is still elusive.

PMID- 16884710
TI  - Increase in intracellular cAMP is a prerequisite signal for initiation of
      physiological oocyte meiotic maturation in the hydrozoan Cytaeis uchidae.
AB  - In medusae of the hydrozoan Cytaeis uchidae, oocyte meiotic maturation and
      spawning occur as a consequence of dark-light transition. In this study, we
      investigated the mechanism underlying the initiation of meiotic maturation using
      in vitro (isolated oocytes from ovaries) and in vivo (ovarian oocytes in medusae)
      systems. Injection of cAMP derivatives into isolated oocytes induced meiotic
      maturation in a dose-dependent manner. Meiotic maturation was also achieved in
      isolated oocytes preloaded with caged cAMP and exposed to UV irradiation. The
      caged cAMP/UV irradiation-induced meiotic maturation was completely inhibited by
      blockers of protein kinase A (PKA), H-89, KT5720, and Rp-cAMPS. The medusae from
      which most parts of the umbrella were removed (umbrella-free medusae) survived
      for at least 2 weeks, during which time oocyte meiotic maturation and spawning
      occurred. When H-89 and Rp-cAMPS were injected into ovarian oocytes of umbrella
      free medusae within 3 min of dark-light stimulation, meiotic maturation was
      inhibited or delayed. An increase in intracellular cAMP was confirmed by FlCRhR,
      a fluorescent cAMP indicator, in ovarian oocytes exposed to dark-light transition
      as well as in isolated oocytes stimulated by caged cAMP/UV irradiation. These
      results indicate that the cAMP/PKA signaling pathway positively contributes to
      light-triggered physiological oocyte meiotic maturation in Cytaeis uchidae.

PMID- 16884709
TI  - Induction of ROS formation, poly(ADP-ribose) polymerase-1 activation, and cell
      death by PCB126 and PCB153 in human T47D and MDA-MB-231 breast cancer cells.
AB  - The primary purpose of this research is to investigate whether exposure to
      polychlorinated biphenyls (PCBs), i.e. PCB153 and PCB126, is associated with
      induction of reactive oxygen species (ROS), poly(ADP-ribose) polymerase-1 (PARP
      1) activation, and cell death in human T47D and MDA-MB-231 breast cancer cells.
      Results indicated that PCB153 and PCB126 induced concentration- and time
      dependent increases in cytotoxic response and ROS formation in both T47D and MDA
      MB-231 cells. At non-cytotoxic concentrations both PCB153 and PCB126 induced
      decreases in intracellular NAD(P)H and NAD+ in T47D and MDA-MB-231 cells where
      T47D cells were more resistant to PCB-induced reduction in intracellular NAD(P)H
      than MDA-MB-231 cells. Further investigation indicated that three specific PARP
      inhibitors completely blocked PCB-induced decreases in intracellular NAD(P)H in
      both T47D and MDA-MB-231 cells. These results imply that decreases in
      intracellular NAD(P)H in PCB-treated cells may be, in part, due to depletion of
      intracellular NAD+ pool mediated by PARP-1 activation through formation of DNA
      strand breaks. Overall, the extent of cytotoxic response, ROS formation, and PARP
      1 activation generated in T47D and MDA-MB-231 cells was greater for PCB153 than
      for PCB126. In addition, the cytotoxicity induced by PCB153 and PCB126 in both
      T47D and MDA-MB-231 cells was completely blocked by co-treatment of catalase,
      dimethylsulfoxide, cupper (I)-/iron (II)-specific chelators, and CYP1A/2B
      inhibitors. This evidence suggests the involvement of ROS, Cu(I), Fe(II), and
      CYP1A/2B enzymes in mediating the induction of cell death by PCB153 and PCB126.
      Further, antagonism was observed between PCB126 and PCB153 for effects on
      cytotoxic response and ROS formation in T47D and MDA-MB-231 cells. Antagonism was
      also observed between PCB153 and PCB126 in the induction of NAD(P)H depletion at
      lower concentration (<10 microM) in T47D cells, but not in MDA-MB-231 cells. In
      conclusions, results from our investigation suggest that ROS formation induced by
      PCBs is a significant determinant factor in mediating the DNA damage and cell
      death in human breast cancer cells. The data also suggests that the status of
      estrogen receptor alpha may play a role in modulating the PCB-induced oxidative
      DNA damage and cell death in human breast cancer cells.

PMID- 16884712
TI  - Valproate prevents MK801-induced changes in brain-derived neurotrophic factor
      mRNA in the rat brain.
AB  - To investigate whether the anticonvulsant valproate influences the changes in
      brain-derived neurotrophic factor (BDNF) mRNA expression induced by MK801 in rat
      brain, we injected valproate prior to MK801 and observed the changes in the BDNF
      expression 3 h later. MK801 significantly increased BDNF expression in the
      retrosplenial and entorhinal cortex, and these increases were prevented by
      valproate pretreatment. Valproate pretreatment significantly blocked the MK801
      induced increase of BDNF expression in retrosplenial cortex at 3 h, 6 h, and 9 h
      after MK801 injection, suggesting that valproate pretreatment did not delay the
      MK801-induced increase of BDNF expression. However, MK801 significantly decreased
      BDNF expression in the granule cell layer of hippocampus, and valproate
      pretreatment before MK801 potentiated the MK801-induced decrease in BDNF
      expression in granule cell layer. These results indicate that valproate
      pretreatment differentially affects the MK801-induced changes in BDNF expression
      in a region-selective manner.

PMID- 16884711
TI  - Genetic manipulation of blood group carbohydrates alters development and
      pathfinding of primary sensory axons of the olfactory systems.
AB  - Primary sensory neurons in the vertebrate olfactory systems are characterised by
      the differential expression of distinct cell surface carbohydrates. We show here
      that the histo-blood group H carbohydrate is expressed by primary sensory neurons
      in both the main and accessory olfactory systems while the blood group A
      carbohydrate is expressed by a subset of vomeronasal neurons in the developing
      accessory olfactory system. We have used both loss-of-function and gain-of
      function approaches to manipulate expression of these carbohydrates in the
      olfactory system. In null mutant mice lacking the alpha(1,2)fucosyltransferase
      FUT1, the absence of blood group H carbohydrate resulted in the delayed
      maturation of the glomerular layer of the main olfactory bulb. In addition,
      ubiquitous expression of blood group A on olfactory axons in gain-of-function
      transgenic mice caused mis-routing of axons in the glomerular layer of the main
      olfactory bulb and led to exuberant growth of vomeronasal axons in the accessory
      olfactory bulb. These results provide in vivo evidence for a role of specific
      cell surface carbohydrates during development of the olfactory nerve pathways.

PMID- 16884713
TI  - Fibroblast growth factor-2 induces the activation of Src through Fes, which
      regulates focal adhesion disassembly.
AB  - Cell migration is regulated by focal adhesion (FA) turnover. Fibroblast growth
      factor-2 (FGF-2) induces FA disassembly in the murine brain capillary endothelial
      cell line IBE, leading to FGF-2-directed chemotaxis. We previously showed that
      activation of Src and Fes by FGF-2 was involved in chemotaxis of IBE cells. In
      this study, we examined the interplay between Src and Fes. FGF-2 treatment
      decreased the number of FA in IBE cells, but not in cells expressing dominant
      negative Fes (denoted KE5-15 cells). FGF-2 induced the activation of Src and
      subsequent binding to and phosphorylation of Cas in IBE cells, but not in KE5-15
      cells. Focal adhesion kinase (FAK) activation and tyrosine phosphorylation by Src
      were also delayed in KE5-15 cells compared to parental cells. FGF-2 induced
      activation of Src within FA in IBE cells, but not in KE5-15 cells. Downregulation
      of Fes or FAK using small interfering RNA diminished Src activation by FGF-2
      within FA. These findings suggest that activation of Fes by FGF-2 enhances FAK
      dependent activation of Src within FA, promoting FGF-2-induced disassembly of
      focal adhesions.

PMID- 16884714
TI  - Neuroprotective effect of topiramate on hypoxic ischemic brain injury in neonatal
      rats.
AB  - Perinatal hypoxia-ischemia is one of the most common risk factors for neonatal
      mortality and permanent neurodevelopmental disability. Topiramate [2,3:4,5-bis-o
      (1-methylethylidene) beta-D-fructo-pyranose sulfamate; TPM] is widely used as an
      antiepileptic agent with multiple targets. In the present study, we found that
      treatment with TPM reduced the neuronal damage induced by oxygen-glucose
      deprivation in vitro with strong inhibition of the alpha-amino-3-hydroxy-5-methyl
      4-isoxazolepropionate (AMPA) receptor. Because perinatal hypoxia is mediated, at
      least in part, by aberrant glutamatergic excitation, we tested whether treatment
      with TPM was effective against perinatal brain hypoxia-ischemia. Intraperitoneal
      or oral pretreatment with TPM was found to reduce the brain damage and subsequent
      cognitive impairments induced by transient hypoxia-ischemia in perinatal rats. A
      potent neuroprotective effect of TPM was also observed in a post-treatment regime
      although post-treatment window appears to be relatively narrow (<2 h). These
      results suggest that TPM treatment may be beneficial for perinatal hypoxia
      ischemia and related damage.

PMID- 16884715
TI  - Copper complexes of (-)-epicatechin gallate and (-)-epigallocatechin gallate act
      as inhibitors of Ribonuclease A.
AB  - Green tea polyphenols, which have the ability to inhibit angiogenesis, form
      complexes with Cu(II), a known potent stimulator of blood vessel proliferation.
      Copper complexes of (-)-epicatechin gallate and (-)-epigallocatechin gallate were
      found to inhibit the enzymatic activity of Ribonuclease A (RNase A) as revealed
      by an agarose gel based assay and urea denatured gel electrophoresis. The copper
      complexes were found to be non-competitive inhibitors of RNase A with inhibition
      constants in the micromolar range. Changes in the secondary structure of the
      protein are found to occur due to the interaction as revealed from Fourier
      transform infrared and circular dichroism studies.

PMID- 16884717
TI  - Saccharomyces cerevisiae telomerase subunit Est3p binds DNA and RNA and
      stimulates unwinding of RNA/DNA heteroduplexes.
AB  - Telomerase is a key participant of telomere length maintenance system in majority
      of eukaryotes. It synthesizes telomere repeats at 3'-end of telomere DNA
      according to its own RNA template. In addition to the reverse transcriptase
      subunit Est2p and telomerase RNA TLC1, yeast telomerase contain Est1p, necessary
      for telomerase attachment to telomere and telomerase activation, and Est3p, a
      subunit with unknown function. We have isolated Est3p and examined its
      biochemical properties. Est3p binds both DNA and RNA oligonucleotides containing
      telomere repeat sequences and stimulates dissociation of RNA/DNA heteroduplexes.
      The importance of these properties of Est3p for telomerase function is discussed.

PMID- 16884718
TI  - Pellino proteins are more than scaffold proteins in TLR/IL-1R signalling: a role
      as novel RING E3-ubiquitin-ligases.
AB  - Members of the Toll-like receptor (TLR) and IL-1 receptor (IL-1R) family initiate
      signalling pathways that shape innate immunity. Pellino proteins have recently
      been implicated as evolutionary conserved scaffold proteins in TLR/IL-1R
      signalling leading to nuclear factor-kappaB and mitogen activated protein kinase
      dependent gene expression. We found that Pellino proteins contain a new RING-like
      motif. Because RING motifs are a feature of a subclass of E3-ubiquitin-ligases
      that target specific proteins for ubiquitination, we suggest that Pellino
      proteins are involved in TLR/IL-1R signalling not only as scaffold proteins but
      also as RING E3-ubiquitin-ligases. In support of this hypothesis we show that
      Pellino proteins induce IRAK-1 polyubiquitination in a RING-dependent manner. We
      further propose a model in which Pellino-mediated IRAK-1 polyubiquitination
      regulates TLR/IL-1R signalling.

PMID- 16884719
TI  - Allosteric activation of antithrombin is independent of charge neutralization or
      reversal in the heparin binding site.
AB  - We investigate the hypothesis that heparin activates antithrombin (AT) by
      relieving electrostatic strain within helix D. Mutation of residues K125 and R129
      to either Ala or Glu abrogated heparin binding, but did not activate AT towards
      inhibition of factors IXa or Xa. However, substitution of residues C-terminal to
      helix D (R132 and K133) to Ala had minimal effect on heparin affinity but
      resulted in appreciable activation. We conclude that charge neutralization or
      reversal in the heparin binding site does not drive the activating conformational
      change of AT, and that the role of helix D elongation is to stabilize the
      activated state.

PMID- 16884720
TI  - Traffic of prion protein between different compartments on the neuronal surface,
      and the propagation of prion disease.
AB  - The key mechanism in prion disease is the conversion of cellular prion protein
      into an altered, pathogenic conformation, in which cellular mechanisms play a
      poorly understood role. Both forms of prion protein are lipid-anchored and reside
      in rafts that appear to protect the native conformation against conversion.
      Neurons rapidly traffic their cellular prion protein out of its lipid rafts to be
      endocytosed via coated pits before recycling back to the cell surface. It is
      argued in this review that understanding the mechanism of this trafficking holds
      the key to understanding the cellular role in the conformational conversion of
      prion protein.

PMID- 16884721
TI  - Plasma steroids and steroid-binding capacity in male semelparous dasyurid
      marsupials (Phascogale tapoatafa) that survive beyond the breeding season in
      captivity.
AB  - The semelparous dasyurids display a unique life history, in that all males die
      within a few weeks of the completion of the breeding season. Studies of several
      semelparous species have revealed that the male die-off is stress-related, and
      accompanied by increased plasma androgen and cortisol levels and decreased
      corticosteroid binding capacity, resulting in suppression of immune and
      inflammatory responses. This study examines the endocrine profile of male brush
      tailed phascogales (Phascogale tapoatafa) that survive beyond the breeding season
      in captivity. Plasma cortisol, corticosteroid binding globulin and albumin levels
      were monitored in both males and females and steroid partitioning calculated.
      Captive males surviving beyond the breeding season did not show the elevation in
      plasma cortisol and decrease in corticosteroid binding capacity reported in wild
      males. Plasma albumin concentrations also remained constant during the sampling
      period. These data indicate that captive males do not undergo the same stress
      response described in wild populations.

PMID- 16884722
TI  - Isolation of the alligator (Alligator mississippiensis) thyroid hormone receptor
      alpha and beta transcripts and their responsiveness to thyroid stimulating
      hormone.
AB  - Thyroid hormones (THs) play key regulatory roles in growth, development and
      metabolism in vertebrates. Modulation of the cellular hormonal response is
      largely through the activity of two nuclear TH receptors, TRalpha and TRbeta,
      which act as transcription factors and alter gene expression programs. Little
      information is available regarding their structure and regulation in reptiles. We
      have cloned the expressed sequences encoding these two receptors in the American
      alligator, Alligator mississippiensis. The encoded putative proteins share a high
      degree of amino acid sequence conservation with other vertebrates, however, both
      alligator TRs contain putative N-terminal truncations. This phenomenon is shared
      with the chicken for TRbeta, but not for TRalpha, making this the first
      demonstration of this type of TRalpha isoform. We measured the steady-state
      levels of TR transcripts in heart, lung, liver, thyroid, cliterophallus/phallus,
      and gonad of juvenile alligators 24 and 48 h after injection with thyroid
      stimulating hormone (TSH). TRalpha transcript levels were increased in the heart,
      decreased in the lung and cliterophallus/phallus, and unaffected in the liver,
      thyroid, and gonad. TRbeta transcript levels were increased in the heart, lung,
      and gonad whereas estrogen receptor alpha transcript levels were elevated by TSH
      treatment only in the gonad. Modulation of these transcripts in the gonad is
      consistent with TH playing an important role in this tissue's function since
      seasonal TH fluctuations coincide with reproductive events. These data
      demonstrate that alligator tissues are differentially responsive to TSH by
      regulation of TR expression and provide an important comparative framework among
      vertebrates.

PMID- 16884723
TI  - Prolactin gene expression and gill chloride cell activity in fugu Takifugu
      rubripes exposed to a hypoosmotic environment.
AB  - To evaluate a possible involvement of prolactin (PRL) in low-salinity tolerance
      of a marine pufferfish Takifugu rubripes, or fugu, gene-expression profiles of
      PRL in the pituitary and PRL receptor (PRLR) in the osmoregulatory organs were
      investigated in fish exposed to 25%-dilute seawater (SW). Following transfer from
      full-strength (100%) SW to 25% SW, plasma osmolality and Na(+) and Cl(-) levels
      were slightly decreased on day 1, which were restored on days 3 and 7. Expression
      levels of PRL mRNA in the pituitary was significantly increased in response to
      25% SW transfer, which was in sharp contrast with a remarkable decrease in growth
      hormone (GH) mRNA levels. These profiles suggest that PRL and GH are involved in
      hyper- and hypoosmoregulation, respectively, as is the case with euryhaline
      teleosts. Expression levels of PRLR mRNA in the gill and intestine were not
      significantly different from the initial levels, whereas, PRLR mRNA expression in
      the kidney was significantly higher on day 7 than the initial levels. Although
      transfer to 25% SW did not affect the average size of Na(+)/K(+)-ATPase
      immunoreactive chloride cells in the gills, both size and density of apical
      openings of chloride cells became significantly smaller after transfer to 25% SW.
      These findings suggest that the possible hypoosmotic action of PRL is mediated by
      PRLR expressed in the osmoregulatory organs, and that low-salinity tolerance of
      fugu may involve reduction of an ion-secreting function of gill chloride cells.
      To further evaluate long-term effects of the low-salinity environment on growth
      and osmoregulation, fugu were raised in 25% and 100% SW for a prolonged period of
      8 weeks. They grew similarly in 25% and 100% SW, and there was no significant
      difference in body weight and standard length at any weekly sampling point. The
      plasma osmolality was maintained at about 345mOsm/kg.H(2)O in both media, whereas
      the gill Na(+)/K(+)-ATPase activity was significantly lower in 25% SW than 100%
      SW. Gene expression of PRL in the pituitary was higher in 25% SW than in 100% SW;
      conversely, expression levels of GH were lower in 25% SW than in 100% SW. These
      findings support a hyperosmotic action of PRL and a hypoosmotic, rather than
      growth-promoting, action of GH in this marine teleost.

PMID- 16884724
TI  - Impairment of spatial learning by estradiol treatment in female mice is
      attenuated by estradiol exposure during development.
AB  - High doses of estradiol (E(2)) can impair spatial learning in the Morris water
      maze, in ovariectomized mice, but the same dose has no effect on adult castrated
      males. Here, we test the hypothesis that this sex difference is caused by
      neonatal actions of E(2). In Experiment 1, C57BL/6J pups were given daily
      estradiol benzoate (EB) or oil injections from the day of birth until postnatal
      Day 3. Adults were gonadectomized and received EB (s.c.) or oil 28 h before the
      first day of training, and 4 h before each of four daily training sessions on the
      Morris water maze. Females given oil as neonates, and EB prior to training
      displayed the poorest performance. Females that received EB as neonates and EB
      prior to training were insensitive to the deleterious effects of adult EB and
      performed better than males given the same hormone treatments. We conducted a
      second experiment using aromatase enzyme knockout (ArKO) mice. Adult male and
      female ArKO and wild-type (WT) littermates were gonadectomized and received
      either injections of oil or EB prior to and during water maze training (as
      described above). Hormone treatment failed to affect performance, yet, female but
      not male ArKO mice showed impaired learning compared to WT littermates. Thus,
      exposure to estradiol during neonatal development can counteract the deleterious
      effects of EB on adult spatial learning.

PMID- 16884725
TI  - The neuroscience of affiliation: forging links between basic and clinical
      research on neuropeptides and social behavior.
AB  - Animal studies point to the role of two neuropeptides-oxytocin and vasopressin-in
      the regulation of affiliative behaviors including mating, pair-bond formation,
      maternal/parenting behavior, and attachment. These findings may have important
      implications for understanding and treating clinical disorders marked by social
      deficits and/or disrupted attachment. This review focuses on advances made to
      date in the effort to forge links between basic and clinical research in the area
      of neuropeptides and social behavior. The literature on oxytocin and its
      involvement in stress response, affiliation, and prosocial behavior is reviewed,
      and the implications of these findings for such disorders as autism as well as
      other social and stress-related disorders including social phobia, post-traumatic
      stress disorder, and some personality disorders are considered. Finally,
      unresolved issues and directions for future research are discussed.

PMID- 16884726
TI  - Estrogen treatment effects on cognition, memory and mood in male-to-female
      transsexuals.
AB  - Gonadal hormones, particularly estrogens, have been suggested to influence memory
      and cognitive tasks that show sex differences. Previously, we reported that male
      to-female (M-F) transsexuals undergoing estrogen treatment for sex re-assignment
      scored higher on verbal Paired Associate Learning (PAL) than a transsexual
      control group awaiting estrogen treatment. The present study used a more robust
      design to examine further associations between estrogen and cognition. We
      assessed additional aspects of memory, including visual, spatial, object and
      location memory, other cognitive abilities that show reliable sex differences,
      including verbal and visual-spatial abilities, and mood variables that could
      mediate associations between estrogen and cognition. In addition to comparing
      groups of individuals on and off estrogen, we used two repeated measures designs
      (AB and BA). The AB group was tested prior to hormone treatment and then again
      after treatment had begun; the BA group was tested while on estrogen treatment
      and then again when hormones had been withdrawn prior to surgery. Few changes in
      memory or cognition were observed, and changes that were observed were not
      consistent across study designs. The lack of significant effects did not relate
      to mood changes or to the sexual orientation of participants. These findings
      suggest that estrogen treatment associated with sex change for M-F transsexuals
      has little or no influence on sex-typed aspects of cognition or memory.

PMID- 16884727
TI  - High-density lipoprotein cholesterol regulates endothelial progenitor cells by
      increasing eNOS and preventing apoptosis.
AB  - OBJECTIVE: Endothelial progenitor cells (EPCs) are implicated as an important
      marker of endothelial function and cardiovascular risk. In the present study, we
      examined whether high-density lipoprotein (HDL) cholesterol plays a role in the
      peripheral EPC levels and its underlying mechanisms in the HDL cholesterol
      induced elevation of EPCs. METHODS: For the clinical study, vascular risk factors
      and blood markers were measured and EPC colony forming units were counted after 7
      days of culture. For the in vitro study, after 7 days of culture, EPCs were
      incubated in the presence or absence of HDL for 24h followed by measurements of
      eNOS and pro-MMP-9 expression and caspase-3 activity. RESULTS: EPC colony levels
      significantly correlated with HDL levels (P=0.017). HDL treatment significantly
      increased eNOS protein expression in EPCs (P<0.001) while it significantly
      decreased pro-MMP-9 levels at the concentration of 50 microg/mL (P=0.002).
      Homocysteine treatment significantly increased caspase-3 activity whereas HDL
      significantly decreased it as compared to the homocysteine-only treated group.
      INTERPRETATION: The data demonstrate that EPC colony levels are significantly
      lower in individuals with low HDL and that HDL increases eNOS and decreases pro
      MMP-9 in EPCs. HDL also prevents EPC apoptosis through inhibition of caspase-3
      activity suggesting a possible mechanism for its positive effects on circulating
      EPC numbers.

PMID- 16884728
TI  - Determination of the Poisson's ratio of the cell: Recovery properties of
      chondrocytes after release from complete micropipette aspiration (Trickey et al.,
      Journal of Biomechanics, 39 (2006) 78-87.

PMID- 16884729
TI  - Multiple response optimisation based on desirability functions of a microwave
      assisted extraction method for the simultaneous determination of chloroanisoles
      and chlorophenols in oak barrel sawdust.
AB  - A microwave-assisted extraction (MAE) method was optimised for extracting 2,4,6
      trichloroanisole (TCA), 2,3,4,6-tetrachloroanisole (TeCA), pentachloroanisole
      (PCA), 2,4,6-trichlorophenol (TCP), 2,3,4,6-tetrachlorophenol (TeCP) and
      pentachlorophenol (PCP) from oak barrels. The method was optimised by using a
      central composite experimental design with extraction time, temperature and
      solvent volume as influential parameters. A desirability function was then
      employed in addition to the simultaneous optimisation of the compounds. The
      optimal conditions identified were temperature 130 degrees C, solvent volume 35
      mL and extraction time 50 min. The compounds were determined by gas
      chromatography with electron-capture detection. MAE was compared with
      conventional Soxhlet extraction; the results obtained with MAE were in good
      agreement with those obtained by Soxhlet extraction.

PMID- 16884730
TI  - Quantitation of mercapturic acids from acrylamide and glycidamide in human urine
      using a column switching tool with two trap columns and electrospray tandem mass
      spectrometry.
AB  - A sensitive and specific electrospray tandem mass spectrometry method using a
      column switching unit with two trap columns was established to quantify the
      mercapturates (MAs) of acrylamide (AA) and glycidamide (GA) in human urine. A
      specially endcapped material was applied for trapping the hydrophilic MAs and a
      pre-trap column was used to remove lipophilic compounds from the directly
      injected urine to protect the trap column. The limits of quantitation for AA-MA
      and GA-MA in urine were 0.5 microg/L and 1 microg/L, respectively. Urine was
      spiked with deuterated internal standards and injected directly into LC-MS/MS.
      Urine of smokers (n=13) revealed the highest concentrations of AA-MA and GA-MA in
      the range of 61-706 microg/L and 5-54 microg/L, respectively. Lower levels for AA
      MA (14-102 microg/L) and GA-MA (1-11 microg/L) were detected in non-smokers
      (n=13).

PMID- 16884731
TI  - Multi-step dielectrophoresis for separation of particles.
AB  - A new concept for separation of particles based on repetitive dielectrophoretic
      trapping and release in a flow system is proposed. Calculations using the finite
      element method have been performed to envision the particle behavior and the
      separation effectiveness of the proposed method. As a model system, polystyrene
      beads in deionized water and a micro-flow channel with arrays of interdigited
      electrodes have been used. Results show that the resolution increases as a direct
      function of the number of trap-and-release steps, and that a difference in size
      will have a larger influence on the separation than a difference in other
      dielectrophoretic properties. About 200 trap-and-release steps would be required
      to separate particles with a size difference of 0.2%. The enhanced separation
      power of dielectrophoresis with multiple steps could be of great importance, not
      only for fractionation of particles with small differences in size, but also for
      measuring changes in surface conductivity, or for separations based on
      combinations of difference in size and dielectric properties.

PMID- 16884732
TI  - Brainstem circuits that control mastication: do they have anything to say during
      speech?
AB  - Mastication results from the interaction of an intrinsic rhythmical neural
      pattern and sensory feedback from the mouth, muscles and joints. The pattern is
      matched to the physical characteristics of food, but also varies with age. There
      are large differences in masticatory movements among subjects. The intrinsic
      rhythmical pattern is generated by an assembly of neurons called a central
      pattern generator (CPG) located in the pons and medulla. The CPG receives inputs
      from higher centers of the brain, especially from the inferio-lateral region of
      the sensorimotor cortex and from sensory receptors. Mechanoreceptors in the lips
      and oral mucosa, in muscles, and in the periodontal ligaments around the roots of
      the teeth have particularly powerful effects on movement parameters. The central
      pattern generator includes a core group of neurons with intrinsic bursting
      properties, as well as a variety of other neurons that receive inputs from oral
      and muscle spindle afferents. Reorganization of subpopulations of neurons within
      the CPG underlies changes in movement pattern. In addition to controlling
      motoneurons supplying the jaw, tongue, and facial muscles, the CPG also modulates
      reflex circuits. It is proposed that these brainstem circuits also participate in
      the control of human speech. LEARNING OUTCOMES: Readers will be able to: (1)
      describe the general location and function of the central pattern generator for
      mastication, (2) identify the primary nuclei involved in the central pattern
      generator for mastication, (3) describe the general interactions among the
      central pattern generators of speech, mastication, respiration, and locomotion,
      and (4) compare/relate the brainstem systems controlling mastication and speech.

PMID- 16884734
TI  - A novel EGFP-CEM-NKr flow cytometric method for measuring antibody dependent cell
      mediated-cytotoxicity (ADCC) activity in HIV-1 infected individuals.
AB  - Enhanced green fluorescent protein (EGFP) was stably expressed in CEM-NKr cell, a
      natural killer (NK) resistant human T-lymphoblastoid cell line, as EGFP-CEM-NKr
      cells. The cells pulsed with HIV-1 gp120 were then used as target cells for the
      measurement of antibody dependent cell mediated-cytotoxicity (ADCC) by flow
      cytometry. Compromised EGFP-CEM-NKr target cells stained with propidium iodide
      (PI) showed dual (green-red) fluorescent. Kinetic studies demonstrated that the
      sum of ADCC activity measured at 1-h and again at 2-h incubations by this flow
      cytometric method was comparable to the activity at 6 h by the standard chromium
      (51Cr) release assay (CRA). ADCC activity of HIV-1 seropositive sera measured by
      this new technique correlated strongly with that of CRA (Pearson's correlation
      coefficient of 0.832; p-value < 0.001 and intraclass correlation coefficient of
      0.903; p-value < 0.001). The EGFP-CEM-NKr stable cell line provides a novel
      method to measure ADCC activity to HIV-1 gp120 by flow cytometry without pre
      staining or pre-labeling target cells.

PMID- 16884736
TI  - Progress in the development of a unifying hypothesis on the mechanisms underlying
      the electrical and mechanical abnormalities of the failing heart: one step
      backward but two steps forward.

PMID- 16884735
TI  - A new parasite that infects eggs of the mud crab, Scylla serrata, in Australia.
AB  - The mud crab, Scylla serrata, is currently being evaluated for its feasibility
      for mass aquaculture in Australia. As part of the evaluation process, pathogens
      that can affect this species need to be identified. This research note describes
      a possible new parasite that infects the eggs of S. serrata. The parasite was
      discovered in two separate cases (three months apart) in a broodstock research
      program and appears to cause 100% egg mortality. The parasite consists of a
      cluster of cells with rhizoids that appear to function as an anchorage and a
      feeding organ. The individual cells range from 3 to 6 microm with a single
      nucleus. The parasite could not be classified to a phylum by morphology alone.
      However, BLAST analysis of the DNA sequence from a PCR amplicon generated using
      universal 18S ribosomal RNA gene primers indicated similarity to pathogenic
      thraustochytrids, Dermocystidium sp. and Rhinosporidium seeberi. All except R.
      seeberi are protistan parasites of fish and crustaceans. A neighbour-joining
      phylogenetic tree confirmed the homology with the thraustochytrids; however,
      further molecular techniques need to be exploited for absolute classification of
      this new parasite.

PMID- 16884737
TI  - Functional and structural characterization of a thiol peroxidase from
      Mycobacterium tuberculosis.
AB  - A thiol peroxidase (Tpx) from Mycobacterium tuberculosis was functionally
      analyzed. The enzyme shows NADPH-linked peroxidase activity using a thioredoxin
      thioredoxin reductase system as electron donor, and anti-oxidant activity in a
      thiol-dependent metal-catalyzed oxidation system. It reduces H2O2, t-butyl
      hydroperoxide, and cumene hydroperoxide, and is inhibited by sulfhydryl reagents.
      Mutational studies revealed that the peroxidatic (Cys60) and resolving (Cys93)
      cysteine residues are critical amino acids for catalytic activity. The X-ray
      structure determined to a resolution of 1.75 A shows a thioredoxin fold similar
      to that of other peroxiredoxin family members. Superposition with structural
      homologues in oxidized and reduced forms indicates that the M. tuberculosis Tpx
      is a member of the atypical two-Cys peroxiredoxin family. In addition, the short
      distance that separates the Calpha atoms of Cys60 and Cys93 and the location of
      these cysteine residues in unstructured regions may indicate that the M.
      tuberculosis enzyme is oxidized, though the side-chain of Cys60 is poorly
      visible. It is solely in the reduced Streptococcus pneumoniae Tpx structure that
      both residues are part of two distinct helical segments. The M. tuberculosis Tpx
      is dimeric both in solution and in the crystal structure. Amino acid residues
      from both monomers delineate the active site pocket.

PMID- 16884739
TI  - Contribution of monoamine oxidase (MAO) inhibition to tobacco and alcohol
      addiction.
AB  - Whole-body PET-scan studies in brains of tobacco smokers have shown a decrease in
      monoamine oxidase (MAO) activity, which reverts to control level when they quit
      smoking. The observed decrease in MAO activity in smokers is presumably due to
      their exposure to tobacco constituents that possess MAO-inhibiting properties.
      The inhibition of MAO activity seems, however, not to be a unique feature of
      tobacco smoking as subjects with Type II alcoholism have been reported to show a
      similar decrease in MAO activity that reverses when they cease to use alcohol.
      The present review summarizes the data on MAO-inhibiting tobacco constituents and
      explains that the decrease in MAO activity observed in alcoholics is probably due
      to concomitant tobacco use. It is concluded that the inhibition of MAO by
      constituents contained in tobacco and tobacco smoke, enhances the addiction
      induced by tobacco smoking.

PMID- 16884740
TI  - Developmental and hormonal regulation of meltrin beta (ADAM19) expression in
      mouse testes during embryonic and postnatal life.
AB  - More than half of ADAM (a disintegrin and metalloprotease) family members are
      expressed in mammalian male reproductive organs such as testis and epididymis.
      The ADAM19 gene identified in mouse is a member of the ADAM family and is highly
      enriched in testes of a newborn mouse. The present study was performed to
      determine its expression pattern in whole mouse testes in vivo as well as its in
      vitro action and regulation in testis cells from 2-day-old mice. Reverse
      transcriptase polymerase chain reaction (RT-PCR) detected ADAM19 mRNA from 15.5
      days postcoitum (dpc) to 21 days postpartum (dpp), with high expression during
      the perinatal period. Immunohistochemistry demonstrated ADAM19 protein
      localization to the seminiferous cords at both embryonic and postnatal ages
      examined (from 15.5-19.5 dpc to 2 dpp). In particular, we obtained new evidence
      that a neutralizing antibody to ADAM19 had no influence on the proliferation of 2
      dpp testis cells cultured in serum-free medium when compared to controls.
      Interestingly, it inhibited the 2 dpp testis cell proliferation elicited by
      stimulation with 10% FCS (P<0.01) or FSH (P<0.05). Lastly, using a model of 2 dpp
      testis cell cultures and RT-PCR procedures, we demonstrated that follicle
      stimulating-hormone (FSH) reduced the levels of ADAM19 mRNA in a time-dependent
      manner. Taken together, these results indicate that the expression of ADAM19 may
      be subject to regulation by FSH during mouse testis development. Furthermore,
      ADAM19 can act to regulate the proliferation of perinatal testis cells in the
      perinatal period.

PMID- 16884738
TI  - Discoidin domain receptor 2 inhibits fibrillogenesis of collagen type 1.
AB  - Discoidin domain receptors (DDR1 and DDR2) are widely expressed cell-surface
      receptors, which bind to and are activated by collagens, including collagen type
      1. Activation of DDRs and the resulting downstream signaling is known to regulate
      the extracellular matrix. However, little is known about how DDRs interact with
      collagen and its direct impact on collagen regulation. Here, we have established
      that by binding to collagen, the extracellular domain (ECD) of DDR2 inhibits
      collagen fibrillogenesis and alters the morphology of collagen type 1 fibers. Our
      in vitro assays utilized DDR2-Fc fusion proteins, which contain only the ECD of
      DDR2. Using surface plasmon resonance, we confirmed that further oligomerization
      of DDR2-Fc (by means of anti-Fc antibody) greatly enhances its binding to
      immobilized collagen type 1. Collagen turbidity measurements and biochemical
      assays indicated that DDR2 delays the formation of collagen fibrils. Atomic force
      microscopy of soluble collagen revealed that a predominately monomeric state of
      collagen was present with DDR2, while control solutions had an abundance of
      polymeric collagen. Transmission electron microscopy of collagen fibers, showed
      that the native periodic banded structure of collagen fibers was weakened and
      nearly absent in the presence of DDR2. Further, using a cell-based assay we
      demonstrate that overexpression of full length DDR2 inhibits fibrillogenesis of
      collagen type 1. Our results demonstrate a novel and important functional role of
      the DDR2 ECD that may contribute to collagen regulation via modulation of
      fibrillogenesis.

PMID- 16884741
TI  - Arginine vasopressin in the caudate nucleus plays an antinociceptive role in the
      rat.
AB  - Our 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
      caudate nucleus (CdN) of the rat. Microinjection of AVP into the CdN increased
      pain threshold in a dose-dependent manner, while local administration of AVP
      receptor antagonist-d(CH(2))(5)Tyr(Et)DAVP decreased pain threshold. Pain
      stimulation elevated AVP concentration in CdN perfuse liquid. CdN pretreatment
      with AVP-receptor antagonist completely reversed AVP's effect on pain threshold
      in the CdN. The data suggest that AVP in the CdN is involved in antinociception.

PMID- 16884742
TI  - Occurrence of antifouling paint booster biocides in selected harbors and marinas
      inside the Gulf of Napoli: a preliminary survey.

PMID- 16884743
TI  - The effect of age on inhibition of return is independent of non-ocular response
      inhibition.
AB  - Inhibition of return (IOR) refers to the slowing of a response to a target
      stimulus presented in the same location as a previous stimulus. Increased IOR has
      been observed in older adults, despite a reduction in other 'inhibitory'
      processes. However, cue-target tasks have been used in all previous studies and
      because of this, IOR may have been overestimated due to non-ocular response
      inhibition associated with withholding a response from the cue. Could increased
      levels of response inhibition account for the observations of increased IOR in
      older adults? This confound can be circumvented by using a target-target
      paradigm, in which a response is made to all stimuli. We tested three groups of
      24 subjects: young (mean 22.5 years), young-old (mean 61.9 years) and old-old
      (mean 74.8 years). Subjects completed both visual cue-target and target-target
      tasks with identical inter-stimulus intervals of 1400 and 1800ms. IOR magnitude
      increased with age in both the cue-target task and the target-target task.
      Furthermore, the magnitude of visual IOR was found to increase with age even when
      individual differences in baseline response speed were taken into account. Thus,
      there appears to be a genuine increase in IOR magnitude with age.

PMID- 16884744
TI  - Structural characterization of a polysaccharide and a beta-glucan isolated from
      the edible mushroom Flammulina velutipes.
AB  - Two polysaccharides were isolated from the basidiomycete Flammulina velutipes,
      via successive hot extraction with water, 2% and 25% aq. KOH, and then submitted
      to freeze-drying. The precipitate formed by repeated freeze-thawing from the 2%
      aq. KOH extraction PK2 was analyzed by determination of its monosaccharide
      composition, as well as by methylation analyses using GC-MS, mono- ((13)C, (1)H
      NMR) and bidimensional ((1)H (obs.), (13)C HMQC) spectroscopy, and controlled
      Smith degradations. It was established to be a branched beta-glucan, with a main
      chain of (1-->3)-linked-Glcp residues, substituted at O-6 by single-unit beta
      Glcp side chains. The precipitate formed by repeated freeze-thawing from the 25%
      KOH extraction PK25 contained Xyl, Man, and Glc and was heterogeneous by HSPEC
      and extraction with DMSO gave a soluble xylomannan (XM). It was homogeneous with
      a molar mass 30.8 x 10(4)g/mol (dn/dc=0.186). Using the above chemical analyses,
      it was a xylomannan with Man and Xyl in a 3:2 molar ratio. Its main chain
      consisted of (1-->3)-linked alpha-Manp units, mainly substituted at O-4 by beta
      Xylp units or with some beta-Xylp-(1-->3)-beta-Xylp groups.

PMID- 16884745
TI  - Xanthones from Hypericum chinense.
AB  - Six xanthones, 1,3,7-trihydroxy-2-(2-hydroxy-3-methyl-3-butenyl)-xanthone (1),
      1,7-dihydroxy-2,3-[2''-(1-hydroxy-1-methylethyl)-dihydrofurano]-xanthone (2),
      1,3,7-trihydroxy-5-methoxyxanthone (3), 1,7-dihydroxy-5,6-dimethoxyxanthone (4),
      4,5-dihydroxy-2,3-dimethoxyxanthone (5), 1,3-dihydroxy-2,4-dimethoxyxanthone (6)
      and 21 known xanthones were isolated from the leaves and stems of Hypericum
      chinense. Their structures were established based on spectroscopic studies.

PMID- 16884746
TI  - Brassicaceae contain nortropane alkaloids.
AB  - The report of cochlearine, the 3-hydroxybenzoate ester of tropine found in
      Cochlearia officinalis, Brassicaceae, initiated a screening for tropane alkaloids
      in Cochlearia species and for calystegines in further Brassicaceae. All ten
      Cochlearia species investigated contained cochlearine, tropine, and
      pseudotropine. Calystegines, nortropane alkaloids deriving from pseudotropine,
      were also identified in all Cochlearia species and accumulated up to 0.5% dry
      mass in leaves. Brassicaceae species of all major lineages of the family were
      analysed for calystegines. Of the 43 species included in the study, 18
      accumulated calystegines of various structures. This is the first screening of
      Brassicaceae for products of the tropane alkaloid pathway, which is known as
      characteristic for plants of Solanaceae family. The identification of
      calystegines in all branches of the Brassicaceae family including Aethionema, a
      species at the basis of the family, suggests tropane alkaloids as secondary
      compound typical for Brassicaceae.

PMID- 16884748
TI  - 5-Hydroxy-seco-carotenoids from Pittosporum tobira.
AB  - Three 5-hydroxy-seco-carotenoids were isolated from seeds of Pittosporum tobira.
      These structures were determined to be (3S,3'S,5'?)-3,3'-di(tetradecanoyloxy)-5'
      hydroxy-5,6,5',6'-diseco-beta,beta-carotene-5,6,6'-trione (1),
      (3S,5?,3'S,5'R,6'S,9'Z)-3-tetradecanoyloxy-5',6'-epoxy-5,3'-dihydroxy-5',6'
      dihydro-5,6-seco-beta,beta-caroten-6-one (2), and (3S,5?,3'S,5'R,6'R)-3
      tetradecanoyloxy-5,3',5'-trihydroxy-6',7'-didehydro-5',6'-dihydro-5,6-seco
      beta,beta-caroten-6-one (3) based on analysis of UV-vis, IR, FAB MS, and NMR
      spectroscopic data.

PMID- 16884747
TI  - Lipoxygenases during Brassica napus seed germination.
AB  - The peroxidation of polyunsaturated fatty acids is mostly catalyzed by members of
      the lipoxygenase enzyme family. Lipoxygenase products can be metabolized further
      in the oxylipin pathway and are known as signalling substances that play a role
      in plant development as well as in plant responses to wounding and pathogen
      attack. Apart from accumulating data in model plants like Arabidopsis,
      information on the relevance of lipid peroxide metabolism in the crop plant
      oilseed rape is scarce. Thus we aimed to analyze lipoxygenases and oxylipin
      patterns in seedlings of oilseed rape. RNA isolated from 3 day etiolated
      seedlings contains mRNAs for at least two different lipoxygenases. These have
      been cloned as cDNAs and named Bn-Lox-1fl and Bn-Lox-2fl. The protein encoded by
      Bn-Lox-2fl was identified as a 13-lipoxygenase by expression in Escherichia coli.
      The Bn-Lox-1fl yielded an inactive protein when expressed in E. coli. Based on Bn
      Lox-1fl active site determinants and on sequence homology the Bn-Lox-1fl is most
      likely a 9-lipoxygenase. Both genes are expressed in light-grown and etiolated
      cotyledons as well as in leaves. Bn-Lox-2fl protein is more abundant in
      cotyledons of etiolated seedlings than in cotyledons of green seedlings. Both 13-
      and 9-lipoxygenase-derived hydroperoxides can be detected during germination.
      Etiolated seedlings contain more lipoxygenase-derived hydroperoxides in non
      esterified fatty acids than green seedlings. The 13-lipoxygenase derivatives are
      6-8-fold more abundant than the 9-derivatives. Lipoxygenase-derived
      hydroperoxides in esterified lipids are almost not present during germination.
      These results suggest that 13-lipoxygenases acting on free fatty acids dominate
      during B. napus seed germination.

PMID- 16884749
TI  - An unusual homoisoflavanone and a structurally-related dihydrochalcone from
      Polygonum ferrugineum (Polygonaceae).
AB  - The homoisoflavanone 5,7-dihydroxy-6-methoxy-3-(9-hydroxy-phenylmethyl)-chroman-4
      one (1) and its structurally related 2',4',6'-trihydroxy-3'-methoxy-alpha
      hydroxymethyl-beta-hydroxy-dihydrochalcone (2) along with the known pashanone
      (3), flavokawin B (4) and cardamonin or alpinetin chalcone (5) pinostrobin (6)
      and 5,8-dimethoxy-7-hydroxychroman-4-one (7) were isolated from dry leaves of
      Polygonum ferrugineum (Polygonaceae). To our knowledge, this is the first report
      of the isolation of a homoisoflavanone from the Polygonum genus and the
      Polygonaceae family, and could be an important chemotaxonomic finding. In
      addition, the pattern of substitution of this homoisoflavanone is different from
      others previously reported.

PMID- 16884751
TI  - Podoconiosis: a tropical model for gene-environment interactions?
AB  - Podoconiosis (endemic non-filarial elephantiasis) is a geochemical disease
      occurring in individuals exposed to red clay soil derived from alkalic volcanic
      rock. It is a chronic, debilitating disorder and a considerable public health
      problem in at least 10 countries in tropical Africa, Central America and northern
      India. Only a small proportion of individuals exposed to red clay develop disease
      and familial clustering of cases occurs, so we tested the hypothesis that disease
      occurs in genetically susceptible individuals on exposure to an environmental
      element in soil. Using multiple statistical genetic techniques we estimated
      sibling recurrence risk ratio (lambda(s)) and heritability for podoconiosis, and
      conducted segregation analysis on 59 multigenerational affected families from
      Wolaitta Zone, southern Ethiopia. We estimated the lambda(s) to be 5.07. The
      heritability of podoconiosis was estimated to be 0.629 (SE 0.069, P=1x10(-7)).
      Segregation analysis showed that the most parsimonious model was that of an
      autosomal co-dominant major gene. Age and use of footwear were significant
      covariates in the final model. Host genetic factors are important determinants of
      susceptibility to podoconiosis. Identification of the gene(s) involved will lead
      to better understanding of the gene-environment interactions involved in the
      pathogenesis of podoconiosis and other complex multifactorial conditions.

PMID- 16884750
TI  - Production of phenylacetic acid derivatives and 4-epiradicinol in culture by
      Curvularia lunata.
AB  - Phenylacetic acid derivatives, methyl 2-acetyl-3,5-dihydroxyphenylacetate (1) and
      methyl 2-acetyl-5-hydroxy-3-methoxyphenylacetate (3); curvulin or ethyl 2-acetyl
      3,5-dihydroxyphenylacetate (4), a known metabolite of Curvularia siddiqui, and 4
      epiradicinol (5) have been isolated from the culture mycelia of Curvularia lunata
      grown on YMG, a medium consisting of yeast, malt extract and glucose. Compounds
      1, 3 and 4 lack antimicrobial and antioxidant activity, but 4-epiradicinol (5)
      inhibited the growth of Escherichia coli, Staphylococcus aureus, Salmonella
      choleraesuis and Bacillus subtilis. The structures of compounds 1, 3-5 were
      determined by analyses of IR, MS, 1D and 2D NMR data, assisted by chemical shift
      comparison to related and model compounds. The relative stereochemistry of the
      vicinal diol in 5 was determined from the 1H NMR signals for the methyl protons
      of the resulting cyclic acetonide prepared from 5.

PMID- 16884752
TI  - Estrogenic and anti-androgenic activities of 4-nitrophenol in diesel exhaust
      particles.
AB  - A 4-nitrophenol (PNP) isolated from diesel exhaust particles (DEP) has been
      identified as a vasodilator. PNP is also a known degradation product of the
      insecticide parathion. We used uterotrophic and Hershberger assays to study the
      estrogenic and anti-androgenic activities of PNP in-vivo. In ovariectomized
      immature female rats injected subcutaneously with 1, 10, or 100 mg/kg PNP daily
      for 7 days, significant (P<0.05) increases in uterine weight were seen in only
      those receiving 10 or 100 mg/kg PNP. Furthermore, in castrated immature male rats
      implanted with a silastic tube (length, 5 mm) containing crystalline testosterone
      and injected subcutaneously with 0.01, 0.1, or 1 mg/kg PNP daily for 5 days,
      those receiving the doses of 0.1 mg/kg showed significant (P<0.05) weight
      decreases in seminal vesicles, ventral prostate, levator ani plus bulbocavernosus
      muscles, and glans penis. Plasma FSH and LH levels did not change in female rats
      but were significantly (P<0.05) increased in male rats treated with 0.1 mg/kg
      PNP. These results clearly demonstrated that PNP has estrogenic and anti
      androgenic activities in-vivo. Our results therefore suggest that diesel exhaust
      emissions and the degradation of parathion can lead to accumulation of PNP in
      air, water, and soil and thus could have serious deleterious effects on wildlife
      and human health.

PMID- 16884755
TI  - A vibrators alternation stepping ultrasonic motor.
AB  - A new concept of a vibrators alternation stepping ultrasonic motor, based on
      longitudinal vibrations of rectangular Langevin resonators, is presented. The new
      motor fed by a single-phase resource without feedback is capable of bi-directions
      step displacements without accumulative displacement error. The step angle is
      1.44 degrees, when the 150 grooves on the rotor are used in positioning. The
      average rotation speed without load in one step is 16.49-14.65 rad/s, and the
      braking torque is 0.071-0.088 Nm in operating frequency 30 kHz and operation
      voltage 200 V.

PMID- 16884754
TI  - Cytotoxicity and related effects of T-2 toxin on cultured Vero cells.
AB  - T-2 toxin belongs to a group of mycotoxins synthesized by Fusarium fungi that are
      widely encountered as natural contaminants of certain important agricultural
      commodities particularly, cereals. Upon exposure, T-2 toxin causes severe human
      and animal diseases. It is considered to be a major causative agent in fatal
      alimentary toxic aleukia (ATA) in humans. In this study, cytotoxicity and
      apotosis induction by T-2 toxin was investigated in vitro on Vero cell line using
      the MTT and the neutral red viability assays, the induction of lipid
      peroxidation, the decrease of macromolecule levels (protein, DNA and RNA), DNA
      fragmentation and caspase-3-dependent apoptosis induction. Our results showed
      that T-2 toxin reduced cell viability correlated to an impairment of
      macromolecule levels. It also increased MDA formation, induced DNA fragmentation
      showed by DNA laddering patterns on agarose gel electrophoresis. This
      fragmentation is in relation with apoptosis induction which was confirmed by
      activation of caspase-3, and depletion of the mitochondrial membrane potential
      reflecting a mitochondrial dysfunction.

PMID- 16884756
TI  - Mapping of human herpesvirus 6 immediate-early 2 protein transactivation domains.
AB  - The immediate-early 2 (IE2) protein of human herpesvirus 6 (HHV-6) is a potent
      transactivator of multiple cellular and viral promoters. Deletion mutants of HHV
      6 variant A IE2 allowed us to map functional transactivation domains acting on
      complex and minimal promoter sequences. This mapping showed that both the N
      terminal and C-terminal domains of IE2 are required for efficient
      transactivation, and that deletion of the C-terminal (1397-1466) tail of IE2
      drastically reduces both transactivation and the intranuclear distribution of
      IE2. Moreover, we determined that the ATF/CRE binding site within the HHV-6A
      polymerase promoter is not required for efficient transactivation by IE2, whereas
      the R3 repeat region of the putative immediate-early promoter of HHV-6A is
      responsive to and positively regulated by IE2. These results contrast sharply to
      that of human cytomegalovirus (HCMV) IE2, which down-regulates its promoter. Our
      characterization of HHV-6 IE2 transactivating activity provides a better
      understanding of the complex interactions of this protein with the viral and
      cellular transcription machinery and highlights significant differences with the
      IE2 protein of HCMV.

PMID- 16884757
TI  - Effects of monotherapy with (R)-9-(2-phosphonylmethoxypropyl)adenine (PMPA) on
      the evolution of a primary Simian immunodeficiency virus (SIV) isolate.
AB  - Determining the impact of antiretroviral therapy on virus evolution could advance
      the development of improved therapeutics/vaccines against HIV. Toward this goal,
      we analyzed virus burden, quasispecies complexity, and T cell responses in
      SIV/DeltaB670-infected rhesus macaques+/-treatment for 7 months with PMPA (2-30
      weeks postinfection). Treatment divided the animals into two groups: poor
      responders (a reduction of < or =1 log) and responders (> or =2 log reduction) in
      virus burden. Virus evolution in poor responders and untreated controls was
      characterized by expression of a complex quasispecies that evolved as the disease
      progressed. This included the universal loss of a viral genotype selected against
      by in vitro passage in monkey cells and selected for by propagation in human
      cells. In contrast, a good response to PMPA was characterized by infection with a
      less complex quasispecies that evolved more slowly. Interestingly, in 2 of the
      best responders, the human-preferred genotype persisted until the study was
      discontinued (89 weeks p.i.). Neither virus burden nor the magnitude of the T
      cell response at 2 weeks postinfection predicted PMPA responsiveness. However,
      responders expressed a less complex quasispecies than nonresponders prior to
      treatment. These data suggest a role for intrinsic host factors in treatment
      responsiveness, and lend support for therapeutic vaccination as an adjunct to
      effective therapy.

PMID- 16884759
TI  - Filtering activity of Spongia officinalis var. adriatica (Schmidt) (Porifera,
      Demospongiae) on bacterioplankton: implications for bioremediation of polluted
      seawater.
AB  - A study on the filtering activity has been carried out on reared specimens of the
      demosponge Spongia officinalis var. adriatica coming from an off-shore farm
      displaced off the Apulian coast (Ionian Sea). The experience was carried out
      under laboratory conditions, by using natural seawater collected from the sponge
      environment. The study demonstrates a high efficiency of the sponge in removing
      bacteria. Bacterial concentration significantly decreases in presence of the
      sponge, with a marked drop after 2 h from the start of the experience. The
      maximum clearance rate was 210 ml h(-1) g(-1) DW at 60 min. Retention efficiency
      reached the highest value of 61% at 120 min. The bacterial density removed by the
      S. officinalis filtering activity was 12.3 +/- 1.8 x 10(4) cells ml(-1)
      corresponding to a biomass of about 11.7 +/- 1.4 microg Cl(-1). The sponge fed
      preferentially large- and medium-size bacteria, whereas the small ones are fed
      after the removal of the largest size categories. The results obtained suggest
      that S. offcinalis is a suitable species for marine environmental bioremediation.

PMID- 16884758
TI  - An unusual X-linked retinoschisis phenotype and biochemical characterization of
      the W112C RS1 mutation.
AB  - A 52-year-old subject harboring an RS1 gene W112C mutation presented with a
      prominent and asymmetric tapetal-like retinal sheen. Transient ERG responses were
      smaller and slower in the eye with the more extensive sheen, an association that,
      to our knowledge, had not been previously reported. An ON-pathway dysfunction
      explained the abnormalities of the transient but not those of the flicker ERGs.
      Although in vitro studies showed that the W112C mutant retinoschisin is present
      only in the cellular fraction and is not secreted, disease expression was
      remarkably mild, consistent with the notion of the existence of genetic and/or
      epigenetic disease modifiers.

PMID- 16884760
TI  - Investigating synergism during sequential inactivation of Bacillus subtilis
      spores with several disinfectants.
AB  - The sequential application of ozone, chlorine dioxide, or UV followed by free
      chlorine was performed to investigate the synergistic inactivation of Bacillus
      subtilis spores. The greatest synergism was observed when chlorine dioxide was
      used as a primary disinfectant followed by secondary disinfection with free
      chlorine. A lesser synergistic effect was observed when ozone was used as the
      primary disinfectant, but no synergism was observed when UV was used as the
      primary disinfectant. When free chlorine was used as the primary disinfectant
      (i.e., sequential application in the reverse order), the synergistic effect was
      shown only when chlorine dioxide was applied as the secondary disinfectant. The
      synergistic effect observed could be related to damage to the spore coat during
      primary disinfection, suggested by the loss of proteins from spores during
      disinfectant treatment. The greatest synergism observed by the chlorine
      dioxide/free chlorine pair suggested that common reaction sites might exist for
      these disinfectants. The concept of percent synergistic effect was introduced to
      quantitatively compare the extent of synergistic effects in the sequential
      disinfection processes.

PMID- 16884761
TI  - Persistent organic pollutants (POP) in a benthic omnivore--a comparison between
      lake and stream crayfish populations.
AB  - We investigated the accumulation of PCB and DDT in crayfish populations in 10
      streams in southern Sweden. The results were compared with an earlier study on
      crayfish in lakes from the same area. We found that the concentration of
      pollutants in crayfish did not differ between the two types of systems. Variation
      in body burden was higher in stream living crayfish probably because of the
      higher influence from pollutants deposited in the catchment area and the more
      dynamic transport in streams. In streams, p,p'-DDE concentrations were positively
      correlated to trophic status (total phosphorous) while PCB did not show any
      correlation with the nutrient regime. Further, mean SigmaPCB and p,p'-DDE
      concentrations in crayfish did not correlate in streams. We suggest that the
      sources of the two pollutants differ for stream living crayfish. The results
      indicate that crayfish in streams are affected to a higher degree to pollutants
      in the catchment area and the precipitation regime. In lakes, internal processes
      govern uptake of pollutants in crayfish.

PMID- 16884763
TI  - Antioxidant responses and reactive oxygen species generation in different body
      regions of the estuarine polychaeta Laeonereis acuta (Nereididae).
AB  - The aim of this study was to analyze the total antioxidant capacity (TOSC),
      generation of reactive oxygen species (ROS) and lipid peroxidation (LPO) in the
      different body regions of the estuarine polychaeta Laeonereis acuta (Nereididae)
      sampled at non-polluted (NOPOL) and polluted (POL) sites from Lagoa dos Patos
      (Southern Brazil). Organisms collected at POL during summer showed similar
      (p>0.05) TOSC values along the body, but worms collected at NOPOL presented
      higher (p<0.05) TOSC values in the posterior (P) region in respect of anterior
      (A) region and middle (M) region. TOSC in the P region at NOPOL was higher
      (p<0.05) compared with the same body region of worms at POL. In summer, ROS
      concentration was higher in A and M regions of worms at POL in respect of the
      organisms at NOPOL. During winter all the regions showed higher ROS in worms
      sampled at POL. It was registered absence of season influence on LPO content, but
      in the P region at NOPOL in summer there were lower LPO levels compared with the
      others regions (p<0.05). In vitro assays showed that P region, despite a higher
      basal ROS, presented a higher competence to cope with pro-oxidants compared with
      A and M regions (p<0.05), corroborating the field results. A lower proteic
      sulfhydril content was observed in P in respect of the other regions (p<0.05)
      supporting the idea of a highest oxidant condition in this region. The results
      indicate that worms collected at the POL site are confronted to higher ROS
      concentrations, affecting its antioxidant capacity, a result that depends of body
      regions.

PMID- 16884762
TI  - Simultaneous quantification of polycyclic aromatic hydrocarbons (PAHs),
      polychlorinated biphenyls (PCBs), and pharmaceuticals and personal care products
      (PPCPs) in Mississippi river water, in New Orleans, Louisiana, USA.
AB  - An effective analytical method for simultaneously determining 16 polycyclic
      aromatic hydrocarbons (PAHs), 28 polychlorinated biphenyl (PCBs), and 12
      pharmaceuticals and personal care products (PPCPs) has been developed to measure
      their concentrations in the Mississippi river waters in New Orleans, Louisiana,
      USA. The method involves the simultaneous extraction of the selected PAHs, PCBs,
      and PPCPs, from the aqueous phase by solid phase extraction using two-layer disks
      consisting of C(18) and SDB-XC, and collection of suspended solid in water
      samples by 0.2-0.6 microm filter in a single step. Target compounds adsorbed on
      the extraction disks were eluted with methanol, acetone, and dichloromethane. The
      suspended particles retained by the filter were sonically extracted using the
      same solvents. GC/MS was used for quantification of PAHs and PCBs directly and of
      PPCPs after derivatization. The analytical method was used in a 6-month field
      study of the Mississippi river water for contamination by PAHs, PCBs, and PPCPs
      and the following concentrations (ng/l) have been obtained: clofibric acid (3.2
      26.7), ibuprofen (0-34.0), acetaminophen (24.7-65.2), caffeine (0-38.0), naproxen
      (0-135.2), triclosan (8.8-26.3), bisphenol A (0-147.2), carbamazepine (42.9
      113.7), estrone (0-4.7), 17beta-estradiol (0-4.5), total PAHs (62.9-144.7), and
      total PCBs (22.2-163.4).

PMID- 16884764
TI  - Removal of arsenic from groundwater by micellar-enhanced ultrafiltration (MEUF).
AB  - The removal characteristics of arsenate using micellar-enhanced ultrafiltration
      (MEUF) were investigated. Among four different cationic surfactants used,
      hexadecylpyridinium chloride (CPC) showed the highest removal efficiency of
      arsenic (96%), and the removal efficiency with hexadecyltrimethylammonium bromide
      (CTAB) was 94%. But the removal efficiency with benzalkonium chloride (BC) was
      the lowest (57%) due to higher critical micelle concentration (CMC) of BC than
      those of other surfactants. Over 80% of arsenic was removed with octadecylamine
      acetate (ODA). On the effect of solution pH on the arsenic removal, since the
      valance of arsenate decreases from trivalent to monovalent as pH decreases, the
      removal was reduced at lower pH. The presence of 0.45mM of nitrate and 0.01mM of
      phosphate reduced the removal efficiency by 5-8%. This decrease was because of
      the competition between the arsenate, nitrate and phosphate for the binding sites
      of the surfactant micelle. Similar decrease in the removal of arsenate was
      observed with CPC, CTAB and ODA in the presence of these anions. In cross-flow
      filtration, the removal efficiency of arsenic was similar to that in the dead-end
      system. However, the decline in flux was less than that in dead-end filtration.
      In order to lower the concentration of the surfactant in the effluent, the
      effluent was treated with powdered activated carbon (PAC) before discharging to
      the environment. Over 98% surfactant was removed with 1gl(-1) of PAC. In
      conclusions, the MEUF is considered as a feasible process using CPC or CTAB to
      remove the arsenate from groundwater compared with the other solid based
      adsorbent processes.

PMID- 16884765
TI  - Stromal cell-derived factor 1alpha stimulates human endometrial carcinoma cell
      growth through the activation of both extracellular signal-regulated kinase 1/2
      and Akt.
AB  - OBJECTIVE: The aim of study was to investigate the proliferative effects of
      stromal cell-derived factor-1alpha (SDF-1alpha) on endometrial carcinomas cell
      lines with different estrogen receptors (ER) and PTEN protein profiles. METHODS:
      MTT assays was used to detect the proliferation of HEC-1A and Ishikawa cells, and
      Western blotted analysis was used to detect activation of Akt and ERK1/2 in both
      cell lines after exposure to various concentrations of SDF-1alpha, MAPK-specific
      inhibitor PD98059 or PI3K-specific inhibitor LY294002. RESULTS: Low
      concentrations of SDF-1alpha (<or=50 ng/ml) significantly promoted proliferation
      of Ishikawa cells but not of HEC-1A, while high concentrations of SDF-1alpha (>50
      ng/ml) induced proliferation in both cell lines. ERK1/2 was significantly
      activated for more than 2 h by SDF-1alpha at 20 ng/ml in HEC-1A cells, but not in
      Ishikawa cells. In contrast, Akt was significantly activated for over 2 h in
      Ishikawa cells but remained unchanged in HEC-1A cells. High concentrations of SDF
      1alpha activated Akt and ERK1/2 pathways in both cell lines in a dose-dependent
      manner, which was primarily inhibited by LY294002 for pAkt and by PD98059 for
      pERK 1/2. CONCLUSIONS: SDF-1alpha could stimulate the cell proliferation of
      endometrial carcinoma with different expression status of ER and PTEN in vitro,
      likely through the activation of both Akt and ERK1/2 signaling pathways.

PMID- 16884766
TI  - The co-occurrence of adolescent boys' and girls' use of psychologically,
      physically, and sexually abusive behaviours in their dating relationships.
AB  - We examined the co-occurrence of and risk factors for adolescent boys' and girls'
      self-reported use of psychologically, physically, and sexually abusive behaviours
      in their dating relationships. The participants were 324 boys and 309 girls in
      grades 7, 9, or 11 who completed surveys at school. Descriptive analyses showed
      that 19% of boys and 26% of girls reported having used two or more forms of
      dating violence. One third of students in grade 7 had already used at least one
      form of aggressive behaviour in this context. Canonical correlation analyses
      indicated that boys' and girls' use of multiple forms of dating violence were
      predicted by their attitudes toward and experiences with violence. After
      controlling for general abusiveness, boys' use of sexually abusive behaviour and
      girls' use of psychologically abusive behaviour were linked to specific risk
      factors that suggest an enactment of social scripts associated with their
      respective gender roles.

PMID- 16884767
TI  - Three-dimensional cell colonization in a sulfate rich environment.
AB  - Glycosaminoglycans (GAGs) have been explored for regenerating various tissues due
      to their involvement in diverse bioregulatory activity. However, understanding
      their influence on cell colonization in three-dimension (3-D) has been difficult
      due to variation in their molecular weight, degree of sulfation, and lack of in
      vitro models. This research focused on developing an in vitro model and
      evaluating the influence of MW (5, 10, and 500 kDa) of negatively charged dextran
      sulfate (DS), a semisynthetic GAG analog, on cell colonization. DS was combined
      with chitosan, a positively charged polymer in solution and porous 3-D matrices
      were formed inside 24-well plates using controlled rate freezing and
      lyophilization technique by two schemes: (i) chitosan structures were formed and
      then allowed to react with DS; (ii) DS was reacted with chitosan in solution and
      then matrices were formed. Scanning electron microscopy analysis showed that
      forming matrices after reacting DS with chitosan was more suitable for tissue
      regeneration. Analysis for the quantity and stability of DS by toluidine blue
      assay indicated significant presence of DS in the 3-D matrices even after seven
      days of incubation in phosphate buffered saline solution. Matrices formed by
      reacting 4% 5 kDa, 2% 10 kDa and 1% 500 kDa DS solution with chitosan had optimum
      porosity and mechanical stability. Next, 25,000 fibroblasts per matrix were
      seeded onto 3-D matrices and analyzed for proliferation by MTT-formazan assay,
      cytoskeletal organization by actin staining, and histological analysis by H/E
      staining. These results showed that cell growth was better on low MW containing 2
      D membranes but high MW DS containing 3-D matrix supported cell growth similar to
      chitosan. Also, cells showed peripheral actin distribution in 3-D matrices.
      Analysis of fibronectin binding by ELISA showed negligible binding to all the DS
      containing matrices, unlike chitosan. In summary, results show cell colonization
      on negatively charged matrices, similar to chitosan.

PMID- 16884768
TI  - 3-D microwell culture of human embryonic stem cells.
AB  - Human embryonic stem cells (hESCs) have the ability to proliferate indefinitely
      and differentiate into each of the embryonic cell lineages. Great care is
      required to maintain undifferentiated hESC cultures since spontaneous
      differentiation often occurs in culture, presumably resulting from soluble
      factors, cell-cell contact, and/or cell-matrix signaling. hESC differentiation is
      typically stimulated via generation of embryoid bodies (EBs) and lineage
      commitment of individual cells depends upon numerous cues throughout the EB
      environment, including EB shape and size. Common EB formation protocols, however,
      produce a very heterogeneous size distribution, perhaps reducing efficiency of
      directed differentiation. We have developed a 3-D microwell-based method to
      maintain undifferentiated hESC cultures for weeks without passaging using
      physical and extracellular matrix patterning constraints to limit colony growth.
      Over 90% of hESCs cultured in microwells for 2-3 weeks were viable and expressed
      the hESC transcription marker Oct-4. Upon passaging to Matrigel-coated tissue
      culture-treated polystyrene dishes (TCPS), microwell cultured hESCs maintained
      undifferentiated proliferation. Microwell culture also permits formation of hESC
      colonies with a defined size, which can then be used to form monodisperse EBs.
      When cultured in this system, hESCs retained pluripotency and self-renewal, and
      were able to be passaged to standard unconstrained culture conditions.

PMID- 16884769
TI  - Spectroscopic translation of cell-material interactions.
AB  - The characterization of cellular interactions with a biomaterial surface is
      important to the development of novel biomaterials. Traditional methods used to
      characterize processes such as cellular adhesion and differentiation on
      biomaterials can be time consuming, and destructive, and are not amenable to
      quantitative assessment in situ. As the development of novel biomaterials shifts
      towards small-scale, combinatorial, and high throughput approaches, new
      techniques will be required to rapidly screen and characterize cell/biomaterial
      interactions. Towards this goal, we assessed the feasibility of using 4
      dimensional elastic light-scattering fingerprinting (4D-ELF) to describe the
      differentiation of human aortic smooth muscle cells (HASMCs), as well as the
      adhesion, and apoptotic processes of human aortic endothelial cells (HAECs), in a
      quantitative and non-perturbing manner. HASMC and HAEC were cultured under
      conditions to induce cell differentiation, attachment, and apoptosis which were
      evaluated via immunohistochemistry, microscopy, biochemistry, and 4D-ELF. The
      results show that 4D-ELF detected changes in the size distributions of
      subcellular organelles and structures that were associated with these specific
      cellular processes. 4D-ELF is a novel way to assess cell phenotype, strength of
      adhesion, and the onset of apoptosis on a biomaterial surface and could
      potentially be used as a rapid and quantitative screening tool to provide a more
      in-depth understanding of cell/biomaterial interactions.

PMID- 16884770
TI  - A role for the intracellular protease calpain in the activation of store-operated
      calcium entry in human platelets.
AB  - Here, we report a novel role for the cysteine protease calpain in store-operated
      calcium entry. Several structurally and mechanistically unrelated inhibitors of
      calpain inhibited Ca2+ entry activated in human platelets by thapsigargin-evoked
      Ca2+ store depletion or the physiological agonist thrombin, whereas inhibitors of
      other cysteine proteases were without effect. The use of the cell-permeable
      fluorogenic calpain substrate 7-amino-4-chloromethylcoumarin, t-BOC-l-leucyl-l
      methionine amide revealed rapid activation of calpain which was closely
      temporally correlated with Ca2+ store depletion even in the absence of a rise in
      cytosolic [Ca2+]. Calpain inhibition prevented the tyrosine phosphorylation of
      several proteins upon Ca2+ store depletion, suggesting that calpain may lie
      upstream of protein tyrosine phosphorylation that is known to be required for the
      activation of store-operated Ca2+ entry in human platelets. Earlier studies using
      calpain inhibitors may need reinterpretation in the light of this finding that
      calpain plays a role in the activation of physiological Ca2+ entry pathways.

PMID- 16884771
TI  - Reduction of intracellular pH inhibits the expression of VEGF in K562 cells after
      targeted inhibition of the Na+/H+ exchanger.
AB  - To explore the effect of inhibition of Na(+)/H(+) exchanger isoform 1 (NHE1) on
      the expression of vascular endothelial growth factor (VEGF) mRNA and protein in
      human myeloid K562 cells. The expression of VEGFmRNA was detected by RT-PCR
      technique. The levels of VEGF protein were measured by Western blotting and
      immunocytochemistry assay. pHi values were measured with fluorescence
      spectrophotometer. The three RT-PCR products detected were VEGF121, VEGF165, and
      VEGF189, respectively. Treatment of K562 cells either with amiloride (an
      inhibitor of NHE1) or with 5-(N-ethyl-N-isopropyl)-amiloride (EIPA, a selective
      inhibitor of NHE1) resulted in significant decrease of VEGF mRNA and VEGF protein
      levels. Either amiloride or EIPA decreased intracellular pH (pHi) values in K562
      cells. These data strongly suggested that the expression of VEGF mRNA and protein
      in K562 cells was inhibited accompanying its reduction in pHi value after
      targeted inhibition of NHE1.

PMID- 16884772
TI  - Molecular basis for decreased folylpoly-gamma-glutamate synthetase expression in
      a methotrexate resistant CCRF-CEM mutant cell line.
AB  - A CCRF-CEM mutant, CEM-p, has been shown to exhibit resistance to methotrexate
      due to decreased methotrexate polyglutamate accumulation. To ascertain the
      mechanism(s) responsible for this phenotype, we analyzed FPGS and SLC19A1 mRNA
      expression, examined FPGS promoter activity, and determined nucleotide sequence
      of the FPGS promoter and full length cDNA from CCRF-CEM and CEM-p cells. We
      identified in FPGS from CEM-p cells three amino acid substitutions that altered
      the ATP binding P-loop, glutamate/folate binding, and a conserved domain located
      at the carboxyl-terminal. Our data demonstrated for the first time the importance
      of the highly conserved domain (VTGSLHLVGGV) located at the carboxyl-terminal for
      FPGS activity.

PMID- 16884775
TI  - The early transcriptional response of pig small intestinal mucosa to invasion by
      Salmonella enterica serovar typhimurium DT104.
AB  - Salmonella enterica serovar typhimurium (S. typhimurium) species are a leading
      cause of human invasive gastroenteritis. There is increasing in vitro evidence
      about Salmonella interaction with isolated cells or cell lines (macrophages, and
      enterocytes) on the molecular level, however, very little is known about in vivo
      interactions during actual invasion. We investigated the early interaction of S.
      typhimurium with intact small intestinal mucosa, in a pig model. Intestinal
      segments were infected with or without S. typhimurium DT104, and perfused. Whole
      mucosal gene expression was analyzed by cDNA array on 0, 2, 4, and 8h post
      infection. Invasion resulted in the upregulation of only eight transcripts in
      jejunal mucosa, among those the proinflammatory IL-8 (at 4h only), and the
      antiinflammatory STAT3 (at 4 and 8h). The limited number of differentially
      expressed genes found here in vivo compared to in vitro is most likely due to the
      presence of multiple, heterogenous cell interactions in intact mucosa.
      Furthermore, it is concluded that S. typhimurium evades strong host responses by
      downregulating the local inflammatory response.

PMID- 16884773
TI  - Textile sludge application to non-productive soil: physico-chemical and
      phytotoxicity aspects.
AB  - As part of an assessment study on the risk of spreading textile sludge onto non
      productive soil, the sorption behaviour of some sludge-metal constituents
      [Cr(VI), Cu(II), Pb(II), and Zn(II)] in the soil was studied. In addition, the
      sludge stabilization effect was evaluated by the biodegradation of organic
      compounds and phytotoxicity tests. Metal-soil sorption was assessed using soil
      columns and by sorption isotherms (i.e., Freundlich and Langmuir). In relation to
      the phytotoxicity of Eruca sativa L., there was a biomass inhibitory effect for
      the fresh sludge and a biomass stimulant effect for the stabilized sludge. Thus
      our results show that after stabilization, the tested loading ratio of 33%
      sludge: 67% soil (v/v) (equivalent to 85 Mg ha(-1)) did not significantly
      increase the risk of groundwater contamination since only small amounts of metals
      applied to the soil underwent percolation and almost all the organic compounds
      were degraded.

PMID- 16884774
TI  - Alternative roles for CD59.
AB  - CD59 was first identified as a regulator of the terminal pathway of complement,
      which acts by binding to the C8/C9 components of the assembling membrane attack
      complex (MAC), to inhibit formation of the lytic pore. Structurally, CD59 is a
      small, highly glycosylated, GPI-linked protein, with a wide expression profile.
      Functionally, the role of CD59 in complement regulation is well-defined but
      studies have also shown clear evidence for signalling properties, which are
      linked to its glycophosphatidyl inositol (GPI) anchor and its location within
      lipid rafts. Cross-linking of CD59 using specific monoclonal antibodies drives
      both calcium release and activation of lipid-raft associated signalling molecules
      such as tyrosine kinases. These observations clearly show that CD59 exhibits
      roles independent of its function as a complement inhibitor. In this review, we
      examine the progression of research in this area and explore the alternative
      functions of CD59 that have recently been defined.

PMID- 16884776
TI  - Visual outcomes in children with juvenile idiopathic arthritis-associated
      uveitis.
AB  - PURPOSE: To analyze visual outcomes in children affected by juvenile idiopathic
      arthritis (JIA)-associated uveitis. DESIGN: Retrospective interventional case
      series. PARTICIPANTS: Eighty-nine children with JIA-associated uveitis. METHODS:
      Charts of children with JIA-associated uveitis were reviewed. MAIN OUTCOME
      MEASURE: Change in patients' visual acuities (VAs). RESULTS: Of 269 children with
      uveitic syndromes referred, 89 (33%) had JIA-associated uveitis. The process was
      bilateral in 76 children. Seventy-three patients were female, and 84% of patients
      were Caucasian. Mean age of onset of uveitis was 5.7 years. Mean follow-up was
      2.96 years. Antinuclear antibody positivity was detected in 56 patients, 44 of
      them female. Patients with JIA-associated uveitis developed numerous
      complications in the course of their disease: of 165 affected eyes, 105 (64%)
      developed cataracts, 33 (20%) developed increased intraocular pressure, and 76
      (46%) developed band keratopathy; posterior synechiae were present in 96 (58%).
      Of 89 children, 73% were treated with immunomodulators, 40% were treated with
      nonsteroidal antiinflammatory agents alone or in combination with
      immunomodulators, and 21% were treated with topical and/or systemic steroids. Of
      65 children who required immunomodulation, only one chemotherapeutic agent was
      used in 30, two agents in 21, and > or =3 in 14. Visual acuities of 65 children
      (122 eyes) were documented and compared at standard intervals. By mixed-models
      linear regression, improvement in VA of 0.03 logarithm of the minimum angle of
      resolution units per year was not found to be statistically significant (standard
      error, 0.02, P = 0.089). CONCLUSIONS: Juvenile idiopathic arthritis-associated
      uveitis is a sight-threatening disease. However, much of the children's vision
      can be preserved if patients are treated appropriately.

PMID- 16884778
TI  - Prevalence of a normal C-reactive protein with an elevated erythrocyte
      sedimentation rate in biopsy-proven giant cell arteritis.
AB  - OBJECTIVE: The erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)
      are laboratory tests that have been said to have a strong correlation with a
      positive temporal artery biopsy in patients with suspected giant cell arteritis
      (GCA). Published reports suggest that the CRP is a more sensitive diagnostic
      indicator of GCA and can be elevated when the ESR is normal. It is also clear
      that the CRP and ESR can both be normal or both be elevated in patients with
      biopsy-proven GCA and that the CRP can be elevated when the ESR is normal. The
      purpose of this study was to ascertain if the CRP can be normal when the ESR is
      elevated in biopsy-proven GCA. DESIGN: Retrospective, longitudinal, comparative
      study. PARTICIPANTS: One hundred nineteen patients from 6 major tertiary-care
      university-affiliated medical centers. METHODS: The charts from 119 patients with
      temporal artery biopsies positive for GCA were reviewed for age, gender,
      pretreatment ESR, and pretreatment CRP. MAIN OUTCOME MEASURES: The ESR in
      millimeters per hour Westergren was graded as normal or abnormal based on 2
      validated formulas. The CRP was graded as normal or abnormal based on established
      criteria set forth in the literature as well as at The Johns Hopkins Hematology
      laboratory. RESULTS: In this study, the ESR had a sensitivity of 76% to 86%,
      depending on which of 2 formulas were used, whereas an elevated CRP had a
      sensitivity of 97.5%. The sensitivity of the ESR and CRP together was 99%. Only 1
      of the 119 patients (0.8%) presented with a normal ESR and normal CRP (double
      false negative); 2 patients (1.7%) had a normal CRP despite an elevated ESR
      according to both formulas. CONCLUSION: Although most patients with GCA have both
      an elevated ESR and CRP, there can be nonconcordance of the 2 blood tests.
      Although such nonconcordance is most often a normal ESR but an elevated CRP, the
      finding of an elevated ESR and a normal CRP also is consistent with GCA. The use
      of both tests provides a slightly greater sensitivity for the diagnosis of GCA
      than the use of either test alone.

PMID- 16884777
TI  - Is diabetes mellitus a risk factor for open-angle glaucoma? The Rotterdam Study.
AB  - PURPOSE: To investigate whether diabetes mellitus is a risk factor for open-angle
      glaucoma (OAG). DESIGN: Prospective population-based cohort study. PARTICIPANTS:
      Participants ages > or =55 years from the Rotterdam Study, The Netherlands.
      METHODS: Participants at risk for incident OAG (iOAG) underwent at baseline (1990
      1993) and follow-up (1997-1999) the same ophthalmic examination including
      intraocular pressure (IOP) measurement, visual field testing, and simultaneous
      stereo optic disc photography. At baseline, diabetes mellitus was defined as the
      use of antidiabetic medication and/or a random or postload glucose value > or
      =11.1 mmol/l. The diagnosis of OAG was made with an algorithm based on optic disc
      measures and visual fields, independent of the IOP. MAIN OUTCOME MEASURE:
      Incident OAG. RESULTS: In total, 3837 participants without OAG at baseline were
      reexamined. After a mean follow-up time of 6.5 years, iOAG developed in 87
      persons. The relative risk of iOAG associated with baseline diabetes was 0.82
      (0.33-2.05). After adjustment for age, gender, follow-up time, IOP, IOP-lowering
      treatment, body mass index, and systemic hypertension, the relative risk of iOAG
      was 0.65 (0.25-1.64). CONCLUSIONS: In this prospective population-based study,
      diabetes mellitus was not a risk factor for OAG.

PMID- 16884780
TI  - Subperiosteal midface lift with or without a hard palate mucosal graft for
      correction of lower eyelid retraction.
AB  - PURPOSE: To compare functional and surgical outcomes of a subperiosteal midface
      lift with and without the placement of a hard palate mucosal graft (HPMG) in
      patients with lower eyelid retraction. DESIGN: Retrospective, comparative,
      interventional case series. PARTICIPANTS: Thirty-four patients with lower eyelid
      retractions who underwent surgery at the Jules Stein Eye Institute in a 5-year
      period. METHODS: Medical record review of all patients who underwent surgery for
      lower eyelid retraction by a subperiosteal midface lift with or without an HPMG.
      Preoperative and postoperative digital photographs were taken in all patients.
      MAIN OUTCOME MEASURES: Change in margin reflex distance 2 (MRD2), measured from
      the pupillary margin to the upper margin of the lower eyelid; patient discomfort;
      and surgical complications. RESULTS: Thirty-four patients (20 female; mean age,
      64 years) participated in the study; 11 underwent bilateral surgery, with overall
      43 surgeries performed. Eighteen patients (42%) had lower eyelid retraction
      secondary to previous transcutaneous lower eyelid blepharoplasty.
      Postoperatively, patients attained a better lower eyelid position, with
      improvement of lower eyelid height of 1.4 mm (P<0.001, 1-sample t test). Patients
      operated using an HPMG (12 surgeries) achieved a greater reduction in MRD2
      postoperatively as compared with patients operated by subperiosteal midface lift
      alone (31 surgeries; 2.2 mm vs. 1.1 mm, respectively; P = 0.02, Wilcoxon Mann
      Whitney). One patient needed reoperation secondary to symptomatic lower eyelid
      retraction postoperatively. CONCLUSIONS: The subperiosteal midface lift is
      effective in correction of lower eyelid retraction of various causes. The use of
      an HPMG spacer may enhance surgical outcomes and results in a better lower eyelid
      position.

PMID- 16884779
TI  - Efficacy of topical cyclosporine 0.05% for prevention of cornea transplant
      rejection episodes.
AB  - PURPOSE: To assess the incidence of immunologic corneal graft rejection episodes
      in a prospective case series of patients treated 4 times a day with topical
      cyclosporine 0.05%. DESIGN: Prospective, single-center, institutional review
      board-approved study. PARTICIPANTS: Fifty-two cornea transplant recipients
      considered low risk for graft rejection. METHODS: Primary indications for
      transplantation were keratoconus, Fuchs' dystrophy, or nonherpetic,
      nonvascularized scars. Subjects completely tapered off prednisolone acetate 1% by
      13 weeks after transplantation and used topical cyclosporine 0.05% 4 times a day,
      beginning either 1 or 10 weeks posttransplant, with use continued until 1 year
      posttransplant. One subgroup supplemented cyclosporine use with pulsed
      prednisolone acetate 1% dosing, 4 times a day for 4 days every 6 weeks. The
      incidence of immunologic corneal graft rejection episodes was compared with that
      in Fuchs' and keratoconus historical control subjects, who used topical steroids
      a median of 7 months after penetrating keratoplasty. MAIN OUTCOME MEASURE:
      Incidence of immunologic graft rejection episodes. RESULTS: Graft rejection
      episodes occurred earlier and with higher incidence in subjects using
      cyclosporine 0.05% compared with historical control subjects who used steroids
      for a longer period of time (P<0.0001). Cyclosporine subjects who pulse-dosed
      prednisolone had a significantly higher incidence of graft rejection compared
      with those who did not pulse steroids (P = 0.04). CONCLUSION: The results suggest
      that 4 times daily dosing with topical cyclosporine 0.05% is not as effective as
      use of topical prednisolone acetate 1% for prevention of graft rejection episodes
      in low-risk corneal transplants, and that periodic pulsing with corticosteroids
      may increase the risk of rejection episodes.

PMID- 16884781
TI  - Aberrantly flattened responsivity to emotional pictures in paranoid
      schizophrenia.
AB  - To investigate the nature of emotional experience in schizophrenia, we examined
      emotional responses to affective stimuli. Twenty-one outpatients with
      schizophrenia (9 paranoid, 12 nonparanoid) and 20 normal controls rated the
      arousal and valence that they experienced from the presentation of 60 pictures.
      Schizophrenia patients displayed less emotional responsivity to the positive
      stimuli and they displayed diverse responsivity to the negative stimuli, which
      depended upon arousal level. Further analysis, using schizophrenia subtype,
      indicated that nonparanoid patients reported increased negative responsivity and
      decreased positive responsivity, regardless of arousal level. However, paranoid
      schizophrenia patients showed enhanced self-reported experiences of emotion to
      the low arousing stimuli and diminished responsivity to the high arousing
      stimuli. This pattern was robust to the negative stimuli. These findings suggest
      that paranoid schizophrenia patients might suffer from aberrantly flattened
      responses to negative emotional stimuli, and that this may account for paranoid
      tendency and secondary social isolation in paranoid schizophrenia.

PMID- 16884782
TI  - Comparison of binding and effects of Escherichia coli Shiga toxin 1 on bovine and
      ovine granulocytes.
AB  - Granulocytes play a pivotal role in the pathogenesis of Shiga toxin (Stx)
      producing Escherichia coli (STEC) related diseases in humans. Granulocytes are
      attracted and activated by Stxs in the enteric mucosa and are believed to thereby
      contribute to the intestinal inflammation. Mature ruminants, the main reservoir
      hosts of STEC, do not develop pathological changes that can be attributed to the
      Stxs. To prove whether the latter phenomenon correlates with the inability of the
      Stxs to affect granulocytes of ruminants, we investigated the ability of Stx1 to
      bind to granulocytes of cattle and sheep and analysed the effects of Stx1 on
      viability, phagocytosis, and oxidative burst activity. Bovine granulocytes from
      blood and milk did not express Stx1-binding sites even after activation of the
      cells and also were resistant to Stx1. In contrast to bovine granulocytes,
      granulocytes of sheep constitutively expressed Stx1-receptors of the Gb(3)/CD77
      type ex vivo and bound the recombinant B-subunit of Stx1 (rStxB1). Stx1 holotoxin
      induced apoptosis in ovine granulocytes after prolonged incubation (18h) but Stx1
      only slightly altered the phagocytosis and oxidative burst activities. The rStxB1
      had no effect on granulocytes of either species. While arguing in favour of our
      initial hypothesis, that granulocytes of both, cattle and sheep are not activated
      by Stxs, the results of our study are the first evidences for differences in the
      cellular distribution of Stx-receptors in species equally regarded as STEC
      carriers.

PMID- 16884783
TI  - Mycobacterium avium subspecies paratuberculosis infection of cattle does not
      diminish peripheral blood-derived macrophage mycobactericidal activity.
AB  - Ruminants infected with Mycobacterium avium subspecies paratuberculosis
      consistently develop a multibacillary form of disease that is centered on the
      ileum. Mechanisms responsible for failure of macrophage function during
      multibacillary disease are incompletely characterized. Our data suggest that
      mycobactericidal functions are present, and potentially enhanced, in monocyte
      derived macrophages from M. avium subsp. paratuberculosis infected cattle.
      Addition of CD4(+) T cells from infected animals to autologous in vitro infected
      macrophages did not increase bacterial killing. In contrast, CD4(+) T cells from
      non-infected animals did increase bacterial killing in autologous macrophages. In
      macrophages from both infected and non-infected cattle, bacterial killing
      appeared to be independent of interferon-gamma (IFN-gamma) and nitric oxide
      production.

PMID- 16884784
TI  - Intact TRL 9 and type I interferon signaling pathways are required to augment HSV
      1 induced corneal CXCL9 and CXCL10.
AB  - Herpes simplex virus type 1 ocular infection elicits a potent inflammatory
      response including the production of the chemokines, CXCL9 and CXCL10, in mice.
      Since HSV-1 nucleic acid is recognized by pattern receptors including Toll-like
      receptor (TLR) 9, we tested the hypothesis that TLR9 is necessary for the early
      augmentation of CXCL10 following HSV-1 infection. Similar to wild type controls,
      TLR9 deficient mice constitutively expressed CXCL10 in the cornea. Following
      infection or stimulation with the deoxycytidylate-phosphate-deoxyguanylate (CpG)
      motif, CXCL10 levels were significantly elevated in the cornea of wild type but
      not TLR9 or type I interferon receptor deficient mice. The reduced CXCL10
      response in the cornea of TLR deficient mice was correlative with an increase in
      virus shedding and a reduction in neutrophil infiltration. This is the first
      report that shows enhanced CXCL10 expression following neurotropic viral
      replication requires both intact TLR 9 and type I interferon signaling pathways.

PMID- 16884786
TI  - Prevention of recurrent respiratory papillomatosis: role of HPV vaccination.
AB  - Recurrent respiratory papillomatosis is a rare, but devastating, cause of airway
      lesions in children and adults. This disease is caused by human papilloma virus
      subtypes 6 and 11. At this time there are two vaccines in late stages of
      development seeking Food and Drug Administration (FDA) approval to prevent
      cervical cancer, which is also caused by human papilloma virus. One of these
      vaccines has been developed to stimulate immunity to the most common subtypes
      that cause cervical cancer but also includes those responsible for recurrent
      respiratory papillomatosis. With the possibility this could drastically reduce
      the incidence of RRP, the otolaryngology community should advocate for
      implementation of a vaccine program that provides effective prevention of HPV
      infection with subtypes 6 and 11.

PMID- 16884785
TI  - Differential susceptibility of cerebral and cerebellar murine brain microvascular
      endothelial cells to loss of barrier properties in response to inflammatory
      stimuli.
AB  - Multiple sclerosis (MS) is a chronic autoimmune disease whose symptoms are caused
      by an inflammatory invasion of the central nervous system (CNS). The molecular
      pathogenesis of MS includes an increased permeability of the blood brain barrier
      (BBB) along with an inability of the BBB to fulfill its normal function of
      protecting the CNS. The cerebellar BBB seems to be especially vulnerable, as the
      development of experimental autoimmune encephalomyelitis (EAE) as an animal model
      of MS often takes its beginning in the cerebellum. Inflammatory lesion
      development seems to correlate with increased permeability of the local BBB.
      Responsible for the BBB are cerebral and cerebellar capillary endothelial cells.
      We therefore generated an in vitro model of the cerebellar BBB (cerebEND) and
      compared its response to inflammatory stimuli (TNFalpha administration) with a
      cerebral BBB in vitro model (cEND) characterised previously [Forster, C.,
      Silwedel, C., Golenhofen, N., Burek, M., Kietz, S., Mankertz, J., Drenckhahn, D.,
      2005. Occludin as direct target for glucocorticoid-induced improvement of blood
      brain-barrier properties in a murine in vitro system. J. Physiol. 565(Pt 2), 475
      486]. We could demonstrate a faster and more pronounced increase in permeability
      in the cerebellar BBB manifested by reduced transendothelial electrical
      resistance and reduced tight junction protein expression. This cell line cerebEND
      could thus be valuable to identify genes differently expressed within the BBB in
      the future and therefore be helpful in finding new ways of treatment of MS.

PMID- 16884787
TI  - Cloning and expression of functional single-chain Fv antibodies directed against
      NIa and coat proteins of potato virus Y.
AB  - Three single-chain variable fragment (scFv) antibodies recognizing the nuclear
      inclusion a (NIa) and capsid proteins of potato virus Y were obtained from two
      mouse derived hybridoma clones secreting, respectively, an anti-NIa (22-1) and an
      anti-coat protein (136-13) monoclonal antibodies. The first monoclonal antibody
      was able to inhibit in vitro the PVY polyprotein cleavage by blocking the NIa
      protease activity. The amplified scFv cDNAs were first inserted into the TOPO
      vector and then sequenced. Several recombinant E. coli clones carrying the
      accurate scFv sequences were selected and the corresponding cDNAs were subcloned
      in pHEN phagemid and transferred in E. coli strain. The expressed scFv fragments
      showed an antibody activity that recognized the viral target proteins in infected
      tissues. Their activity was comparable to the parental monoclonal antibodies.

PMID- 16884788
TI  - Antiviral activity of Arthrospira-derived spirulan-like substances.
AB  - Natural substances offer interesting pharmacological perspectives for antiviral
      drug development in regard to broad-spectrum antiviral properties and novel modes
      of action. In this study we analyzed polysaccharide fractions isolated from
      Arthrospira platensis. Fractions containing intracellular or extracellular
      spirulan-like molecules showed a pronounced antiviral activity in the absence of
      cytotoxic effects. Using specific assays for the quantification of viral
      replication in vitro, these substances exhibited strong inhibition of human
      cytomegalovirus, herpes simplex virus type 1, human herpesvirus type 6 and human
      immunodeficiency virus type 1, while only weak or no inhibition was noted for
      Epstein-Barr virus and influenza A virus. Considering herpesviruses, antiviral
      effects were most pronounced when the cells were preincubated with the substances
      prior to the addition of virus, indicating that antiviral action may be primarily
      targeted to virus entry. However, an inspection of the inhibition of human
      cytomegalovirus protein synthesis clearly demonstrated that intracellular steps
      also contributed to the antiviral effect. In the case of human immunodeficiency
      virus, inhibition occurred at a stage later than viral entry. Thus, spirulan-like
      substances possess a marked antiherpesviral and anti-HIVactivity based on
      different modes of action. Further development of these substances might yield
      novel candidates of broad-spectrum antiviral drugs.

PMID- 16884789
TI  - Tolerance to the reinforcing effects of morphine in delta9-tetrahydrocannabinol
      treated mice.
AB  - Several studies have investigated interactions between opioid and cannabinoid
      systems. However, the results regarding the rewarding effects of opiates in
      animals pre-exposed to CB1 agonists, appear inconsistent. Using the conditioned
      place preference, it was shown that dependence to delta9-tetrahydrocannabinol
      (THC) was hardly reached, while the synthetic ligand WIN55,212-2 facilitate the
      rewarding effects of morphine. The aim of the present study was to establish
      whether a chronic THC treatment (10 mg/kg, i.p., 21 days) may facilitate, in
      mice, the rewarding effects of morphine used at low doses (0.5 and 2 mg/kg, i.p.)
      or high dose (10 mg/kg, i.p.) after a long drug-free period, as it was speculated
      that chronic cannabinoid exposure may induce long-lasting neural changes in brain
      regions involved in opiate addiction. Moreover, THC was used in conditions as
      close as possible to those leading to cannabis drawbacks. After 15 days of
      abstinence, the locomotor activating properties of morphine as well as its
      motivational properties were not facilitated by pretreatment with THC in mice and
      even reduced for the higher dose of morphine used in the conditioned place
      preference (CPP). This lack of CPP in animals pretreated with THC was not due to
      discrimination impairment between different environments, as demonstrated in a
      two-trial recognition task. In conclusion, it appears that chronic THC treatment
      leads to a reduction of reinforcing effects of morphine in the CPP. This result
      supports the occurrence of modulatory interaction between opioid and cannabinoid
      systems in the reward process.

PMID- 16884790
TI  - Nucleus accumbens lesions decrease sensitivity to rapid changes in the delay to
      reinforcement.
AB  - Both humans and non-humans discount the value of rewards that are delayed or
      uncertain, and individuals that discount delayed rewards at a relatively high
      rate are considered impulsive. To investigate the neural mechanisms that mediate
      delay discounting, the present study examined the effects of excitotoxic lesions
      of the nucleus accumbens (NAC) on discounting of reward value by delay and
      probability. Rats were trained on delay (n=24) or probability discounting (n=24)
      tasks. Following training, excitotoxic lesions of the NAC were made by
      intracranial injections of 0.5 microl 0.15 M quinolinic acid (n=12) or vehicle
      (n=12) aimed at the NAC (AP +1.6, ML +/-1.5, DV -7.1). NAC lesions did not alter
      performance in animals tested with a constant delay (4s) or probability (0.4) of
      reinforcement. However, when tested with between session changes in the delay (0,
      1, 2, 4, and 8s) of reinforcement, the lesioned rats had flatter discount curves
      than the sham group, indicating that they were less sensitive to frequent changes
      in the delay to reward. In contrast, the NAC lesions did not affect discounting
      of probabilistic rewards. NAC lesions impaired the ability to adapt to frequent
      between session changes in the delay to reward but did not increase or decrease
      discounting when the delay was held constant across sessions. NAC lesions may
      disrupt the ability of the animals to predict the timing of delayed rewards when
      the delay to reward is changed frequently.

PMID- 16884791
TI  - Feminization of Japanese medaka (Oryzias latipes) exposed to 17beta-estradiol:
      effect of exposure period on spawning performance in sex-transformed females.
AB  - Two groups of Japanese medaka (Oryzias latipes) were exposed to 17beta-estradiol
      (E2: 150ng/L, nominal concentration) for either a short-term exposure (STE: 0-31
      days after fertilization (daf); egg-larval period) or a long-term exposure period
      (LTE: 0-81 daf; egg-adult period) and their subsequent spawning performance was
      compared in terms of fecundity, spawning time, and fertility. Most genetic males
      were transformed to phenotypic females by E2 following both short-term and long
      term exposure, but spawning performance and gonad somatic index (GSI) of sex
      transformed females (XY females) following long-term exposure were lower than
      those of sex-transformed females following short-term exposure and those of
      normal females (XX) in the control group. Sex-transformed females in the STE
      group and normal females possessed mature ovary, whereas most of the sex
      transformed females in the LTE group possessed immature ovary, with most oocytes
      being in the pre-vitellogenic phase. Moreover, the chromosome types of first
      filial generation delivered from sex-transformed female in STE group composed
      with 51.9% as XY, 18.5% as YY, and 29.6% as XX. From these results, it seems that
      exposure to E2 until the end of the larval period produces sex-transformed medaka
      with high reproductive ability, similar to normal females, but longer exposure to
      E2 may inhibit sexual maturation in the sex-transformed female.

PMID- 16884792
TI  - Human antibodies with muscarinic activity modulate ventricular repolarization:
      basis for electrical disturbance.
AB  - INTRODUCTION: In chronic chagasic patients sudden death has been reported when QT
      interval dispersion is increased and antibodies with muscarinic-like activity
      have been demonstrated to trigger arrhythmias. The aims were to investigate, in
      vivo and in vitro, relation between these antibodies and heterogeneity of
      ventricular repolarization and to identify predictors of cardiac death in chronic
      chagasic patients. METHODS AND RESULTS: Clinical, electrocardiograph and
      echocardiograph variables from 32 chronic chagasic patients with moderate to
      severe left ventricular dysfunction, followed-up for 10 years were analyzed. Sera
      from chronic chagasic patients with or without muscarinic activity were tested in
      isolated rabbit hearts to study ventricular repolarization. Stepwise multivariate
      logistic analysis was applied to identify independent predictors of cardiac
      death. QT interval dispersion of patients with muscarinic activity (75.9+/-5.5
      ms) was larger than that of patients without muscarinic activity (51.3+/-4.0 ms,
      p<0.001). Maximum uncorrected and corrected QT intervals were not significantly
      different between groups of patients. Sera from patients with muscarinic activity
      significantly and reversibly increased QT interval in isolated rabbit hearts
      (p=0.002). This effect was abolished in the presence of the muscarinic antagonist
      atropine. Multivariate analysis identified maximum corrected QT intervals and
      left ventricular end diastolic index as independent predictors of cardiac death
      (p=0.03 and p=0.02, respectively). CONCLUSIONS: Sera with muscarinic activity
      from chagasic patients have a strong contribution to evoke ventricular
      repolarization rhythm disorder. In these patients, ventricular repolarization
      heterogeneity is increased significantly. In vitro, muscarinic sera reversibly
      increased repolarization duration. Maximum corrected QT intervals and left
      ventricular end diastolic index are independent predictors of cardiac death.

PMID- 16884793
TI  - White blood cell count adds prognostic information to the thrombolysis in
      myocardial infarction risk index in patients following primary percutaneous
      coronary intervention (ANIN Myocardial Infarction Registry).
AB  - AIMS: To determine the relationship between baseline white blood cell (WBC)
      count, Thrombolysis in Myocardial Infarction (TIMI) risk index, and 30-day
      mortality in unselected patients with ST-elevation myocardial infarction (STEMI)
      treated with primary mechanical reperfusion (PCI). METHODS AND RESULTS: 903
      patients from prospective registry admitted for primary PCI to a tertiary
      cardiological center. Both baseline WBC count and TIMI risk index data were
      dichotomized about the respective medians. Overall 30-day mortality was 4.3%.
      Higher WBC count was associated with adverse clinical outcome (6.3% vs. 2.4%;
      Kaplan-Meier p=0.004) as were higher TIMI risk index values (7.2% vs. 1.4%;
      Kaplan-Meier p<0.00001). In addition, median WBC count stratified patients within
      TIMI risk index strata into very low risk (0%), intermediate risk (3.3%) and high
      risk (11%) (Kaplan-Meier p=0.023 and p=0.005 for comparison of lower and higher
      WBC count within TIMI risk index stratas). In multivariate analysis WBC count
      provided independent and additional to TIMI risk index predictive information
      (Hosmer-Lemeshow p=0.57 and p=0.88 respectively for predictive value of TIMI risk
      index alone and combined with WBC count). Other independent predictors of death
      were current smoking (RR 0.33; 95% CI: 0.13-0.87) and previous MI (RR 3.13; 95%
      CI: 1.28-7.69). CONCLUSIONS: WBC count may be a simple and useful tool for risk
      stratification in STEMI patients, providing additional to established risk index
      prognostic information. Our findings stress the strong correlation of
      inflammation and poor outcome in STEMI patients, which may indicate directions of
      development of new therapies.

PMID- 16884794
TI  - Blood glutathione as independent marker of lipid peroxidation in heart failure.
AB  - BACKGROUND: Aminothiols have a critical function as intracellular redox buffers
      and constitute furthermore an important extracellular redox system. Lipid
      peroxidation is increased in chronic heart failure (CHF), but the contribution of
      each thiol to oxidative stress in this syndrome has not been evaluated. AIM: To
      assess the correlation between blood and plasma concentrations of aminothiols and
      lipid peroxidation as marker of oxidative stress in CHF patients. METHODS: Blood
      reduced glutathione (GSH), plasma total and reduced cysteine, cysteinylglycine,
      homocysteine, GSH, alpha-tocopherol, ascorbic acid, and free malondialdehyde
      (MDA) were assessed in samples obtained from 26 CHF heart transplant candidates
      and 26 age- and gender-matched controls with atherosclerotic risk factors and no
      history of cardiovascular disease. Results are expressed as median and
      interquartile range (I-III). RESULTS: MDA levels were significantly higher in CHF
      patients than in controls [1.03 (0.56-1.60) microM vs. 0.70 (0.40-0.83) microM,
      p=0.006]. Blood reduced GSH concentrations were significantly higher [662 (327
      867) microM vs. 416 (248-571) microM, p=0.016], while alpha-tocopherol levels
      were significantly lower [15 (13-19) microM vs. 21 (17-32) microM, p=0.001] in
      CHF patients than in controls. By multivariate logistic regression analysis, the
      only independent predictors of lipid peroxidation, as expressed by MDA levels >
      or = 1.00 microM, were increased blood GSH concentrations (OR 1.003 per unit, 95%
      CI 1.001 to 1.006, p=0.008), ischemic (OR 20, 95% CI 2.6 to 155, p=0.004) and non
      ischemic CHF etiology (OR 11, 95% CI 1.3 to 99, p=0.026). CONCLUSIONS:
      Abnormalities in intracellular GSH cycling are associated to increased lipid
      peroxidation in CHF.

PMID- 16884795
TI  - Right atrial mass presenting as cardiac tamponade.
AB  - Intracavitary tumors such as angiosarcomas are prone to embolize, and occlude
      valves and vessels. Intramyocardial tumors cause cardiac failure and arrhythmias.
      Pericardial tumors cause effusions which result in tamponade. It is very rare
      that an intracavitary tumor presents itself with a cardiac tamponade. A 32-year
      old woman presented to the emergency room with palpitation and shortness of
      breath. Her physical examination revealed pulsus paradoxus and jugular venous
      distention. The transthoracic echocardiography showed normal left ventricular
      function, and an intracavitary right atrial mass. As the patients clinical status
      deteriorated an emergency operation was performed. The hemorrhagic pericardial
      fluid was cytologically positive for malignant cells. Histopathological findings
      were indicative of an angiosarcoma.

PMID- 16884796
TI  - Characterization of methods for determining sterilization efficacy and reuse
      efficiency of oxygen biosensor multiwell plates.
AB  - High-throughput screening (HTS) assays based upon fluorometric detection of
      oxygen consumption in microtiter plates were primarily developed for applications
      in drug discovery and ecotoxicology but have recently been adopted for use in
      microbial community-level physiological profiling assays (CLPP). The widespread
      use of oxygen biosensor systems for CLPP applications has, however, been hindered
      by the relatively high cost of oxygen biosensor reagent systems and limited
      access to microplate fluorometer instrumentation platforms. The ability to
      recycle and reuse oxygen biosensor system plates would expand their utilization
      for CLPP assays and other research applications in microbial ecology. Here, the
      efficacy and cost effectiveness of multiple procedures for sterilization of
      Oxygen Biosensor System (OBS; BD Biosciences) plates for reuse was evaluated. OBS
      plates were sterilized using ethylene oxide, ultraviolet radiation, and bleach
      treatments, then evaluated for biosensor response and plate life-cycle
      performance. Of the sterilization methods tested, ethylene oxide sterilization
      was most effective based on its low cost, high sterilization efficacy, and
      minimal impact upon OBS plate response.

PMID- 16884798
TI  - Risk analysis in radiation treatment: application of a new taxonomic structure.
AB  - BACKGROUND AND PURPOSE: Radiation treatment (RT) for cancer is susceptible to
      clinical incidents resulting from human errors and equipment failures. A
      systematic approach to collecting and processing incidents is required to manage
      patient risks. We describe the application of a new taxonomic structure for RT
      that supports risk analysis and organizational learning. MATERIALS AND METHODS: A
      systematic analysis of the RT process identified five process domains. Within
      each domain we defined incident type groups. We then constructed a database
      reflecting this taxonomic structure and populated it with incidents from publicly
      available sources. Querying this database provides insights into the nature and
      relative frequency of incidents in RT. RESULTS: There are relatively few reports
      of incidents in the Prescription domain compared with the Preparation and
      Treatment domains. There are also fewer reports of systematic and infrastructure
      incidents in comparison to sporadic and process incidents. Infrastructure
      incidents are mainly systematic in nature, while process incidents are more
      likely to be sporadic. CONCLUSIONS: The lack of a standard, systems-oriented
      framework for incident reporting makes it difficult to learn from existing
      incident report sources. A clear understanding of the potential consequences and
      relationships between different incident types will guide incident reporting,
      resource allocation, and risk management efforts.

PMID- 16884797
TI  - An improved method for the selective detection of fungi in hospital waters by
      solid phase cytometry.
AB  - Yeast cells and mould spores can be fluorescently labelled with the viability
      stain carboxyfluorescein diacetate (CFDA) and detected on a membrane filter by
      laser scanning (solid phase cytometry, SPC). Although the selectivity of an
      existing commercial SPC procedure for fungi is ensured by using a 2 microm pore
      size membrane filter and a pre-incubation on a proprietary spore
      swelling/activation medium, some bacteria are still co-detected. In the present
      study, the selectivity for fungi has been enhanced by combining the green
      fluorescent CFDA with a second red fluorescent label, i.e. TRITC-concanavalin A,
      targetting fungal but not commonly bacterial cells. Additional improvements
      resulted from the prolongation of the pre-incubation and from the extra-rinsing
      of the membrane filter. The improved method was applied to detect fungi in
      hospital waters, dialysis fluids and endoscopic rinse waters. In general, SPC
      detected more fungi in water than plate methods. The occurrence of fungi in
      dialysis fluid and endoscopic rinse water was rare. Evidence for the presence of
      fungal viable but non-culturable (VBNC) cells in water was weak.

PMID- 16884799
TI  - A comparison of prostate IMRT and helical tomotherapy class solutions.
AB  - The purpose of this study was to assess a variety of potential IMRT class
      solutions as compared to a helical tomotherapy (HT) class solution for localized
      prostate cancer. Target and critical structures were contoured on 10 prostate
      cancer patient CT datasets. HT treatment plans were compared to four different
      IMRT approaches by paired t-tests. HT prostate planning generally provided
      treatment plans with excellent target homogeneity and favorable critical
      structure sparing when compared to conventional IMRT.

PMID- 16884800
TI  - Postural sway and joint kinematics during quiet standing are affected by lumbar
      extensor fatigue.
AB  - The purpose of this study was to investigate changes in postural sway and
      strategy elicited by lumbar extensor muscle fatigue. Specifically, changes in
      center of mass (COM), center of pressure (COP), and joint kinematics during quiet
      standing were determined, as well as selected cross correlations between these
      variables that are indicative of movement strategy. Twelve healthy male
      participants stood quietly both before and after exercises that fatigued the
      lumbar extensors. Whole-body movement and ground reaction force data were
      recorded and used to calculate mean body posture and variability of COM, COP, and
      joint kinematics during quiet standing. Three main findings emerged. First,
      participants adopted a slight forward lean post-fatigue as evidenced by an
      anterior shift of the COM and COP. Second, post-fatigue increases in joint angle
      variability were observed at multiple joints including joints distal to the
      fatigued musculature. Despite these increases, anterior-posterior (AP) ankle
      angle correlated well with AP COM position, suggesting the body still behaved
      similar to an inverted pendulum. Third, global measures of sway based on COM and
      COP were not necessarily indicative of changes in individual joint kinematics.
      Thus, in trying to advance our understanding of how localized fatigue affects
      movement patterns and the postural control system, it appears that joint
      kinematics and/or multivariate measures of postural sway are necessary.

PMID- 16884801
TI  - An oligodendroglial progenitor cell line FBD-102b possibly secretes a radial glia
      inducing factor.
AB  - Interactions between oligodendroglial and astroglial lineages during development
      are still unclear. In this study, FBD-102b, derived from p53-/- fetal brains, was
      characterized as an oligodendroglial progenitor cell (OPC) line. In co-culture
      with 102b cells, cells of an astrocyte progenitor cell line, FBD-104, elongated
      monopolar processes, like radial glia, and actively proliferated. Conditioned
      medium of 102b cells also induced the process elongation that was associated with
      down-regulation of GFAP and up-regulation of vimentin and nestin. These results
      suggested that OPCs secrete a radial glia-inducing factor that might maintain the
      radial glial processes to use as scaffolds of migration.

PMID- 16884802
TI  - Characterization of spontaneous phage-resistant derivatives of Lactobacillus
      delbrueckii commercial strains.
AB  - A total of 44 spontaneous phage-resistant mutants were isolated from three
      commercial Lactobacillus delbrueckii strains by secondary culture and agar plate
      methods. Phenotypic characteristics related to their phage-resistance capacities,
      i.e. plaquing efficiency, phage-resistance stability, lysogeny and adsorption
      rates were determined. The morphological, biochemical (sugar fermentation
      patterns) and technological (acidifying and proteolytic activities and
      acidification kinetics) properties of mutants were also studied. Amplification
      and restriction analysis of the 16S rRNA gene (PCR-ARDRA) was applied to confirm
      strain identity at the subspecies level. Random amplification of polymorphic DNA
      (RAPD-PCR) was used to determine genetic diversity among the isolates and their
      respective parent strains. The secondary culture method was the most useful for
      obtaining phage-resistant mutants. Phage resistance stability was a variable
      property among the isolates, but a high level of resistance was exhibited as
      quantified by the efficiency of plaquing. Furthermore, a total absence of
      spontaneous lysogeny was demonstrated. Adsorption rates were heterogeneously
      distributed among the three groups of mutants. All mutants isolated from two
      sensitive strains were similar to them with respect to technological properties.
      Two groups of mutants with distinctive technological properties were isolated
      from the other sensitive strain. PCR-ARDRA revealed that two out of three
      sensitive strains identified commercially as Lb. delbrueckii subsp. bulgaricus
      were actually Lb. delbrueckii subsp. lactis. Some of the phage-resistant mutants
      that were obtained might be used in culture rotation programs without regulatory
      restrictions when commercial strains become sensitive to phages present in
      industrial environments.

PMID- 16884803
TI  - Microbiological and sensory quality of dry fermented sausages containing alginate
      microencapsulated Lactobacillus reuteri.
AB  - The probiotic bacterium Lactobacillus reuteri was added to dry sausage batter,
      without or after being microencapsulated in alginate using either extrusion or
      emulsion technology. Pediococcus pentosaceus and Staphylococcus carnosus were
      added at 7 log cfu/g as starter cultures for fermentation. The sausage batter was
      stuffed in 55 mm fibrous casings and fermented, with smoking, at <or=26 degrees C
      and 88% relative humidity (RH) for 72 h. During fermentation as well as drying at
      75% RH and 13 degrees C for 25 days, the pH and water activity (a(w)) of the
      sausages were measured. The numbers of the three organisms in sausages during
      processing were determined. A consumer taste panel study was conducted to
      determine if addition of L. reuteri as unencapsulated cells or in microcapsules
      added at 1% (w/w) affected the sensory quality of the dry fermented sausages.
      Changes in sausage pH from 5.8 to 4.8, and a(w) from 0.97 to 0.89, were the same
      for both control and microcapsule-containing sausages. The numbers of
      unencapsulated L. reuteri cells dropped by 2.6 log units, whereas
      microencapsulated L. reuteri were reduced by only <or=0.5 log unit after drying.
      No significant difference in sensory quality was found between control and
      sausages containing either unencapsulated or microencapsulated L. reuteri. Thus,
      microencapsulation of probiotics like L. reuteri may be an option for formulation
      of fermented meat products with viable heath-promoting bacteria.

PMID- 16884804
TI  - Rat, ovine and bovine Peyer's patches mounted in horizontal diffusion chambers
      display sampling function.
AB  - Freshly excised rat, ovine and bovine ileal Peyer's patch (PP) and non-Peyer's
      patch tissues (NPP) were mounted in modified horizontal polyethylene diffusion
      chambers with a range of window areas. Rat tissue was initially used to establish
      that barrier function and histology were maintained for up to 60 min. Horse
      radish peroxidase (HRP) fluxes and S. Typhimurium adherence and invasion were
      significantly higher in rat PP over NPP. Particle uptake was shown to be a rapid,
      energy-, time-, and size-dependent process, occurring more readily in PP than NPP
      tissue in each species. In a kinetic analysis, particles were localized initially
      in the follicle-associated epithelium and then in the dome region. For NPP
      uptake, particles were initially localized to villous epithelium, and were then
      detected in the crypts and lamina propria. Electrophysiological parameters
      including pharmacologically-stimulated inward short-circuit current responses
      were determined in isolated PP and NPP from each species mounted under identical
      conditions in Ussing chambers. In conclusion, comparative functional and
      histological characteristics of PP from several species were demonstrated in
      horizontal diffusion chambers. Horizontal diffusion chambers are therefore a
      useful in vitro model in which a range of functions including transport of
      particulate formulations by PP may be examined.

PMID- 16884805
TI  - Anti-angiogenic inhibition of tumor growth by systemic delivery of PEI-g-PEG
      RGD/pCMV-sFlt-1 complexes in tumor-bearing mice.
AB  - Vascular endothelial growth factor (VEGF) is an endogenous mediator of tumor
      angiogenesis. Blocking associations of the VEGF with its corresponding receptors
      (Flt-1, KDR/flk-1) have become critical for anti-tumor angiogenesis therapy.
      Previously, we synthesized PEI-g-PEG-RGD conjugate and evaluated as an angiogenic
      endothelial polymeric gene carrier. In this study, PEI-g-PEG-RGD/pCMV-sFlt-1
      complexes are evaluated in terms of tumor growth inhibition in vivo. Complexes
      were repeatedly injected systemically via tail vein into subcutaneous tumor
      bearing mice. As a result, tumor growth was inhibited in the PEI-g-PEG-RGD/pCMV
      sFlt-1 injected group. However, this effect was not identified in PEI-g-PEG/pCMV
      sFlt-1 or PEI-g-PEG-RGD/pCMV-GFP control groups. Moreover, the survival rate
      increased in the PEI-g-PEG-RGD/pCMV-sFlt-1 group compared with the controls
      group. These results suggest that delivery of pCMV-sFlt-1 using PEG-g-PEG-RGD may
      be effective for anti-angiogenic gene therapy.

PMID- 16884806
TI  - Heparin-deoxycholic acid chemical conjugate as an anticancer drug carrier and its
      antitumor activity.
AB  - A chemically modified heparin-DOCA (HD) conjugate was developed as a drug carrier
      for cancer therapy. HD conjugate was found to have markedly low anticoagulant
      activity and to form self-assembled nanoparticles in aqueous condition. We
      observed that HD conjugate prevented squamous cell carcinoma (SCC) and human
      umbilical vascular endothelial cell (HUVEC) proliferation during BrdU
      incorporation assays. Here, we prepared doxorubicin-loaded heparin nanoparticles
      by entrapping doxorubicin into the amphiphilic HD conjugate by physical
      interaction and characterized the properties of these nanoparticles using Dynamic
      Light Scattering (DLS) and Atomic Force Microscope (AFM). In this study,
      doxorubicin-loaded heparin nanoparticles were designed to improve the antitumor
      effects of nano-sized particles (range of 180 to 210 nm) at high drug-loading
      efficiencies in the range 64% to 96%. These doxorubicin-loaded heparin
      nanoparticles displayed sustained drug release patterns. It was confirmed in vivo
      toxicity studies that HD conjugate did not induce unexpected side effects and
      that DHN 20 was safer than free DOX. An in vivo study showed that HD conjugate,
      doxorubicin and DHN 20 (one of doxorubicin-loaded heparin nanoparticles) induced
      tumor volume reductions of 43%, 56% and 74%, respectively, relative to the saline
      treated control. These results suggest that the drug-entrapped with heparin
      nanoparticles might provide a novel therapy for SCC.

PMID- 16884807
TI  - Release of anti-restenosis drugs from poly(ethylene oxide)-poly(DL-lactic-co
      glycolic acid) nanoparticles.
AB  - Dexamethasone- or rapamycin-loaded nanoparticles based on poly(ethylene oxide)
      and poly(dl-lactic-co-glycolic acid) block copolymers (PEO-PLGA) were prepared
      without additional stabilizer using the salting-out method. A fast release of
      drug in PBS (pH 7.4) at 37 degrees C resulting in 100% release within 5 h was
      observed for both drugs. The rate of drug release was substantially reduced by
      treating the particles with gelatin or albumin after drug loading, resulting in a
      linear drug release in time. It was shown that the rate of drug release is
      related to the amount of protein associated with the nanoparticles. After gelatin
      treatment of drug-loaded nanoparticles, sustained release of dexamethasone for 17
      days and of rapamycin for 50 days could be achieved.

PMID- 16884808
TI  - Improved intestinal delivery of salmon calcitonin by Lys18-amine specific
      PEGylation: stability, permeability, pharmacokinetic behavior and in vivo
      hypocalcemic efficacy.
AB  - Peptides like salmon calcitonin (sCT) are subjected to aggressive proteolytic
      attack by various intestinal enzymes, and fractions that enter the systemic
      circulation via the intestinal route are rapidly inactivated by tissue
      accumulation and glomerular filtration. Here, we describe the beneficial effects
      of the Lys(18)-amine specific PEGylation of sCT on the intestinal delivery of
      sCT. Two key properties were enhanced by the PEGylation process: (i) the
      resistance of sCT to intestinal enzymes and (ii) the systemic clearance of sCT
      that had entered the circulation. Initially, we evaluated the cAMP-secreting
      activities of PEG(2K)-sCT isomers substituted at Cys(1)-, Lys(11)- or Lys(18)
      amine position in T47D cells, and found that sCT PEGylated at Lys(18)-amine
      (Lys(18)-PEG(2K)-sCT) had the highest bioactivity. We then investigated the
      stability of Lys(18)-PEG(2K)-sCT in the presence of intestinal enzymes, its
      abilities to traverse the intestinal membrane, its pharmacokinetic behavior and
      in vivo hypocalcemic efficacy. Results show that Lys(18)-PEG(2K)-sCT has
      significantly increased resistance to pancreatic peptidases and brush-border
      peptidases. Despite the molecular size increase caused by PEGylation, Lys(18)
      PEG(2K)-sCT was found to have an intestinal permeability similar to that of
      unmodified sCT (p>0.59) over an apical concentration range 12.5-100 microM in a
      Caco-2 cell monolayer transport system. In particular, tissue distribution
      results showed that (125)I-labeled Lys(18)-PEG(2K)-sCT markedly resists liver
      accumulation and glomerular filtration; levels were reduced by 75% and 50% vs.
      sCT. Finally, the hypocalcemic efficacy of intestinally administered Lys(18)
      PEG(2K)-sCT, measured as total serum calcium in a rat model, was 5.8 and 3.0
      times that of sCT at 100 and 200 IU/kg (p<0.025). Our findings suggest that this
      site-specific conjugation of peptides with PEG of proper size enhances
      pharmacokinetic properties by increasing their abilities to resist both
      proteolysis and systemic clearance without significantly reducing their membrane
      permeabilities or bioactivities. We believe that this concept, namely, dual
      effects by PEGylation, has great potential value because it presents a practical
      means of enhancing the efficacies of the peroral/intestinal pharmacologic route.

PMID- 16884809
TI  - A model for predicting delay in discharge of stroke patients.
AB  - AIMS: To study the factors that predict delay in discharge (DD) for stroke
      victims when they are admitted to hospital and to build a model for predicting DD
      in our hospital. METHOD: A retrospective study of 214 stroke victims admitted to
      the Physical Medicine and Rehabilitation Service (PMRS) of a general hospital
      between January 1, 1994, and December 31, 2001. Seventeen clinical and
      sociodemographic data were studied to determine which factors were predictors of
      DD: age, sex, type of stroke, side affected, sphincter control, ability to
      communicate, level of consciousness, deep sensitivity, antecedents of
      cardiovascular risk, delay before admission to the PMRS, initial functional state
      and solitude, whether the patient was employed prior to the cerebrovascular
      accident, and whether the patient's place of residence had any exterior
      architectural barriers. RESULTS: A total of 26.6% of patients experienced DD.
      Factors influencing DD were solitude (odds ratio [OR] 6; 95% confidence interval
      [CI] 2.2-16.1), an initial functional independence measure (FIM) below 50 (OR
      4.5; 95% CI 2.3-8.9) and age greater than 75 years (OR 2.7; 95% CI 1.2-6.1). The
      best model for predicting DD comprises seven variables: solitude, initial FIM
      below 50, older than 75 years, left hemiparesis, exterior architectonic barriers
      at home, cardiovascular antecedents and sex (male). This model has a specificity
      of 89% and a sensitivity of 40%. CONCLUSION: Solitude, low initial FIM and age
      older than 75 years influence DD for patients with stroke admitted to hospital. A
      model for predicting DD is described.

PMID- 16884810
TI  - [Rehabilitation outcomes following knee arthroplasty: a retrospective study of 90
      patients].
AB  - The objective of rehabilitation after arthroplasty is the restoration of
      satisfactory joint amplitude and muscular strength. The objective of this study
      was to determine the reasons for hospitalization for rehabilitation after knee
      arthroplasty, duration of stay and perioperative morbidity. The retrospective and
      descriptive study included 90 patients. The average age of patients was 74.5
      years. A total of 84% of patients underwent primary arthroplasty and 16%
      secondary arthroplasty, with 7% undergoing bilateral arthroplasty. Of the
      patients, 88% displayed a comorbidity; 16% a deficit in flexion or extension. A
      total of 28% were dependents and 43% lived alone at home. Local adverse events
      occurred in 48% of the patients and general adverse events in 59%; deep venous
      thrombosis and/or pulmonary embolism were the most frequently described events
      (15.5%). The duration of stay for rehabilitation was 8.8 days in surgery, and
      19.9 days in a rehabilitation center. The mean duration of stay was the greatest
      for patients with bilateral arthroplasty, those with a serious complications and
      older patients. The factors that determine hospitalization for rehabilitation
      after knee arthroplasty include older age, with comorbidity held constant;
      bilateral or secondary arthroplasty; level of disability; degree of dependence;
      living alone at home; and complications. A short stay in surgery followed by a
      short stay in rehabilitation center is possible with a network management.

PMID- 16884811
TI  - Pharmacy diabetes care program: analysis of two screening methods for undiagnosed
      type 2 diabetes in Australian community pharmacy.
AB  - OBJECTIVE: To compare the efficacy and cost-effectiveness of two methods of
      screening for undiagnosed type 2 diabetes in Australian community pharmacy.
      METHODS: A random sample of 30 pharmacies were allocated into two groups: (i)
      tick test only (TTO); or (ii) sequential screening (SS) method. Both methods used
      the same initial risk assessment for type 2 diabetes. Subjects with one or more
      risk factors in the TTO group were offered a referral to their general
      practitioner (GP). Under the SS method, patients with risk factors were offered a
      capillary blood glucose test and those identified as being at risk referred to a
      GP. The effectiveness and cost-effectiveness of these approaches was assessed.
      RESULTS: A total of 1286 people were screened over a period of 3 months. The rate
      of diagnosis of diabetes was significantly higher for SS compared with the TTO
      method (1.7% versus 0.2%; p=0.008). The SS method resulted in fewer referrals to
      the GP and a higher uptake of referrals than the TTO method and so was the more
      cost-effective screening method. CONCLUSIONS: SS is the superior method from a
      cost and efficacy perspective. It should be considered as the preferred option
      for screening by community based pharmacists in Australia.

PMID- 16884812
TI  - An examination of the moderating effect of treatment with anti-depressants on the
      association of heart disease with depression in males with type 2 diabetes
      attending a Veterans Affairs Medical Center.
AB  - OBJECTIVE: To examine the association of heart disease with depression and the
      impact of treatment with anti-depressants on this association in older males with
      type 2 diabetes. RESEARCH DESIGN AND METHODS: In this cross-sectional study, data
      were collected from the electronic medical record system of the Veterans Affairs
      Medical Center (VAMC) in a large mid-western city in the United States. Subjects
      were 8185 males older than 40, with a history of type 2 diabetes, who had visited
      the VAMC within the previous 6 years. Odds ratios were used to measure bivariate
      associations; multivariate logistic regression was used to adjust for potential
      confounding factors. RESULTS: After adjustments for confounding variables,
      significant associations were found between depression and any adverse heart
      event (OR=1.34, p=0.001), coronary artery disease (OR=1.23, p=0.039), myocardial
      infarction (MI; OR=1.77, p<0.001), and angioplasty (OR=1.36, p=0.034).
      Examination of the interaction between depression and anti-depressant
      prescription status indicated that, except for MI, these associations were no
      longer significant among those who had been prescribed anti-depressants, but
      remained significant and were increased in magnitude among those who had not been
      prescribed anti-depressants. CONCLUSIONS: These findings support the premise that
      co-morbid depression in diabetics is associated with the occurrence of adverse
      heart events, and further suggest that treatment of depression with anti
      depressants moderates this association.

PMID- 16884814
TI  - An analysis of the supplementary health sector in Brazil.
AB  - This paper addresses the efficiency of the Brazilian supplementary health sector.
      Analysis is carried out on the distribution of income in Brazil and the
      supplementary health sector in terms of geographical distribution of the users,
      operators and user health plans. Data envelopment analysis was used to assess the
      financial efficiency of companies operating in the sector. The results reveal
      inefficient financial performance of operators. The paper argues that a minimum
      level of service provided by the public health system is not achieved. The
      evidence reveals a major discrepancy between the government's neoliberal concept
      for the sector and the focus of the operators. The coverage which is incompatible
      with income distribution in Brazil and the low level of public investment per
      person result in the creation of companies which are not focused on the real
      purpose of the supplementary health system.

PMID- 16884813
TI  - The nursing home versus the hospital as the place of dying for nursing home
      residents in Japan.
AB  - OBJECTIVES: To determine the characteristics of nursing home residents that are
      associated with dying in a nursing home versus a hospital in Japan. DESIGN:
      Retrospective case-control study. SETTING: A nonprofit nursing home with 110 beds
      in Tokyo, Japan. PARTICIPANTS: Eighty-six nursing home residents who died in the
      nursing home (n=43) or in a hospital (n=43) between 1 April 1999 and 30 September
      2004. MEASUREMENTS: Nursing home records were reviewed to gain information
      regarding the following domains: demography, the family decision-maker, health
      status, resident and family preference for nursing home end-of-life care, and
      presence of a full-time physician. RESULTS: The variables older age [adjusted
      odds ratio (adjusted OR)=1.08, 95% confidence interval (95% CI)=1.01-1.17], the
      family decision-maker's preference for nursing home end-of-life care (adjusted
      OR=3.95, 95% CI=1.21-12.84), and presence of a full-time physician (adjusted
      OR=3.74, 95% CI=1.03-13.63) were associated with dying in the nursing home.
      CONCLUSION: Older age, the family's preference for nursing home end-of-life care,
      and the presence of a full-time physician were significantly related to dying in
      the nursing home versus in a hospital.

PMID- 16884815
TI  - Determinants of preventive services in general practice. A multilevel approach in
      cardiovascular domain and vaccination in France.
AB  - BACKGROUND: France is in Europe, the country in which the mortality due to
      potentially preventable causes is the highest. At the same time, French doctors
      receive no incentives to undertake prevention activities. This article examined
      the general practitioners' (GPs) determinants (characteristics, patient list and
      contextual factors) of cardiovascular prevention and vaccination carried out by
      GPs in their offices. METHODS: Data were collected from 105,726 patients followed
      by 86 GPs (observational study). A multilevel analysis with two levels: GP and
      patient (HLM) was performed. RESULTS: A high between-GP variability of the
      prevention activity is underlined in both domains. After controlling for patient
      characteristics, we observed a positive effect of the GP's workload (ORa=1.03)
      and of an elderly GP's patient list (ORa=1.04) on cardiovascular prevention, a
      positive effect of a patient list with a high level of health care consumption on
      vaccination activity (ORa=1.04). The significant influence of contextual factors
      is ever more demonstrative: the ORa is 1.3 times lower in cardiovascular
      prevention and 1.6 in vaccination when the density of GPs in the local community
      of the doctor's practice grows of one-point (1/1000); the ORa is two times lower
      in both cardiovascular prevention and vaccination for GPs having an urban
      practice. CONCLUSION: These results emphasize the need for taking into account
      contextual factors to implement prevention policies in primary care. But further
      studies of this type should be conducted by taking other variables into account
      in order to improve the proportion of variance explained in our models.

PMID- 16884816
TI  - Removal of the ocular artifacts from EEG data using a cascaded spatio-temporal
      processing.
AB  - Eye movements and blinks may produce unusual voltage changes in human
      electroencephalogram (EEG). These effects may spread across scalp and mask brain
      signals. In this paper, a cascaded spatio-temporal processing procedure (CAST) is
      presented to remove artifact electrooculogram (EOG). Firstly a discrete
      equivalent distributed source on the cortical surface is reconstructed from the
      contaminated scalp recordings by a linear minimum norm estimation (i.e. a spatial
      analysis step). Then, the equivalent sources of EOG are identified by principal
      component analysis (PCA) of the equivalent distributed source time series (i.e. a
      temporal analysis step). Finally, the EOG-corrected scalp EEG is reconstructed
      from the equivalent distributed source where EOG components have been removed.
      The effectiveness of CAST is confirmed by the application to actual scalp data
      and a detailed comparative study.

PMID- 16884817
TI  - Effects of type of smoking (pipe, cigars or cigarettes) on biological indices of
      tobacco exposure and toxicity.
AB  - Although all forms of smoking are harmful, smoking pipes or cigars is associated
      with lower exposure to the lethal products of tobacco products and lower levels
      of morbidity and mortality than smoking cigarettes. Cytochrome P-450-1A (CYP1A)
      is a major pathway activating carcinogens from tobacco smoke. Our primary aim was
      to compare CYP1A2 activity in individuals smoking pipes or cigars only,
      cigarettes only and in non-smokers. We studied 30 smokers of pipes or cigars
      only, 28 smokers of cigarettes only, and 30 non-smokers male subjects matched for
      age. CYP1A2 activity was assessed as the caffeine metabolic ratio in plasma. One
      day urine collection was used for determining exposure to products of tobacco
      metabolism. Nitrosamine and benzo[a]pyrene DNA adducts were measured in
      lymphocytes. CYP1A2 activity was greater (p<0.0001) in cigarette smokers (median:
      0.61; interquartile range: 0.52-0.76) than in pipe or cigar smokers (0.27; 0.21
      0.37) and non-smokers (0.34; 0.25-0.42) who did not differ significantly. Urinary
      cotinine and 1-hydroxypyrene levels were higher in cigarette smokers than in pipe
      or cigar smokers and higher in the later than in non-smokers. DNA adducts levels
      were significantly lower in pipe or cigar smokers than in cigarette smokers. In
      multivariate analysis, cigarette smoking was the only independent predictor of
      CYP1A2 activity (p<0.0001) and of 1-hydroxypyrene excretion in urine (p=0.0012).
      In this study, pipe or cigar smoking was associated with lower exposure to
      products of tobacco metabolism than cigarette smoking and to an absence of CYP1A2
      induction. Cigarette smoking was the only independent predictor of CYP1A2
      activity in smokers. However, inhalation behaviour, rather than the type of
      tobacco smoked, may be the key factor linked to the extent of tobacco exposure
      and CYP1A2 induction. Our results provide a reasonable explanation for the
      results of epidemiological studies showing pipe or cigar smoking to present fewer
      health hazards than cigarette smoking.

PMID- 16884819
TI  - Hinokiresinol is not a precursor of agatharesinol in the norlignan biosynthetic
      pathway in Japanese cedar.
AB  - The biosynthetic relationship between the two norlignans agatharesinol and trans
      hinokiresinol was investigated. Fresh sapwood sticks of Cryptomeria japonica were
      fed with stable isotope-labeled compounds, namely p-coumaryl alcohol-[9,9-(2)H],
      p-coumaryl alcohol-[9-(18)O] and trans-hinokiresinol-[1-(2)H], and then incubated
      under high-humidity for approximately 20 days, during which the two norlignans
      were produced simultaneously. While trans-hinokiresinol was strongly deuterium
      labeled after feeding with p-coumaryl alcohol-[9,9-(2)H], agatharesinol was only
      lightly labeled after feeding with either p-coumaryl alcohol-[9,9-(2)H] or -[9
      (18)O]. These results suggest that p-coumaryl alcohol, which is a precursor of
      hinokiresinol, is not involved in the biosynthesis of agatharesinol. Therefore,
      the norlignan carbon skeleton of agatharesinol must be framed from different
      types of phenylpropanoid monomers compared to those utilized by the trans
      hinokiresinol pathway. The biosynthesis of these two norlignans seems to branch
      at an early stage, i.e., before the framing of the norlignan carbon skeleton.
      Furthermore, agatharesinol was not labeled with deuterium after feeding with (2)H
      labeled trans-hinokiresinol, which has the simplest norlignan structure. This
      result strongly supports the suggestion that the conversion of trans
      hinokiresinol to agatharesinol is not part of the biosynthesis of norlignans and
      that early branching occurs instead.

PMID- 16884818
TI  - A phase II study with gemcitabine and split-dose cisplatin in patients with
      advanced non-small cell lung cancer.
AB  - BACKGROUND: The combination of gemcitabine and cisplatin is among the most active
      regimens for the treatment of NSCLC. However, the optimal dose and schedule for
      administration of the two drugs has not yet been determined. We investigated the
      activity and toxicity of a gemcitabine and split-dose cisplatin regimen in an
      outpatient setting for patients with advanced non-small cell lung cancer (NSCLC).
      PATIENTS AND METHODS: From June 2004 to May 2005 patients with stage IIIB or IV
      who had not had prior chemotherapy entered the study. Treatment consisted of
      gemcitabine 1250 mg/m2 and cisplatin 35 mg/m2, both given intravenously on days 1
      and 8 every 21 days. RESULTS: Forty-five patients were entered this study.
      Patient characteristics were as follows: male/female, 34/11; median age (range),
      62 (30-76) years; ECOG PS 0/1/2, 7/30/8; stage IIIB/IV, 18/27. A total of 168
      cycles were delivered, with a median of 4 cycles (range, 1-6). All patients were
      evaluable for toxicity. Grade 3 and 4 toxicities according to the NCI toxicity
      criteria included neutropenia in 8 patients (18%), anemia in 4 (9%),
      thrombocytopenia in 7 (15%), and emesis in 1 (2%). Of 42 patients assessable for
      response, 23 patients showed a partial remission. On intent-to-treat basis, the
      overall response rate was 51% (95% CI, 37-65%). Median time to progression was
      6.0 months (range, 1.2-12.0 months) and median overall survival was 13.1 months
      (range, 1.4-17 months). CONCLUSIONS: This regimen with gemcitabine and split-dose
      cisplatin using a 21-day schedule appears to be active and very well-tolerated in
      an outpatients setting for patients with advanced NSCLC.

PMID- 16884820
TI  - Recovery of maize (Zea mays L.) inbreds and hybrids from chilling stress of
      various duration: photosynthesis and antioxidant enzymes.
AB  - The differences between two maize (Zea mays L.) inbred lines and their F1 hybrids
      in their response to chilling periods of various duration (1, 2, 3 or 4 weeks)
      and subsequent return to optimum temperatures were analysed by the measurement of
      the photosystem (PS) 1 and 2 activity, the photosynthetic pigments' content and
      the activity of antioxidant enzymes. The PS2 activity and the chlorophyll content
      decreased in plants subjected to 3 or 4 weeks of chilling, but not in those
      subjected to 1 or 2 weeks of chilling. This decrease was more pronounced in
      inbreds compared to their hybrids. The activity of superoxide dismutase did not
      much change with the increasing length of chilling period in the inbreds but
      decreased in the hybrids, the glutathione reductase activity increased in both
      types of genotypes but more in the inbred lines, while for ascorbate peroxidase
      and catalase the changes in parents-hybrids relationship did not show any
      specific trend. The PS1 activity and the carotenoids' content was not much
      affected.

PMID- 16884821
TI  - Electric and structural studies of hormone interaction with chloroplast envelope
      membranes isolated from vegetative and generative rape.
AB  - The electric and structural properties of envelope membranes of chloroplasts
      obtained from vegetative and generative plants of rape and the effect of hormone
      (IAA, GA(3) and zearalenone) treatment were determined by zeta potential and
      small-angle X-ray scattering (SAXS) methods. Chloroplasts were isolated from
      leaves cut off from the vegetative (before cooling) and generative apical parts
      of plants. The lipid composition of chloroplast envelope membranes were analyzed
      by chromatographic techniques. Envelopes from generative plants contained higher
      levels of digalactosyldiacylglycerol (DGDG) and smaller amounts of phospholipids
      (PLs) in comparison to those obtained from vegetative ones. Moreover, envelopes
      of generative plants were characterized by higher fractions of unsaturated fatty
      acids. The zeta potential changes caused by hormone treatment were higher for
      chloroplasts isolated from vegetative plants in comparison to chloroplasts
      isolated from generative ones. An especially strong effect was observed for
      chloroplasts treated with IAA. The thickness of bilayers of untreated
      chloroplasts from vegetative plants were larger by 0.4 nm when comparing to the
      thickness of layers obtained from generative ones. The effect of hormones (GA(3)
      and zearalenone) was detected only for vegetative chloroplasts. Both applied
      methods indicated differences in the properties of untreated and hormone-treated
      chloroplasts obtained from vegetative and generative plants.

PMID- 16884822
TI  - A novel nodule-enhanced gene encoding a putative universal stress protein from
      Astragalus sinicus.
AB  - A nodule-enhanced gene, AsD243, was identified from infected roots of Astragalus
      sinicus using suppressive subtractive hybridization (SSH). It encodes a 20-kD
      protein related to the bacterial universal stress protein family (Usp). Sequence
      analysis showed that AsD243 is highly similar to the bacterial MJ0577-type of ATP
      binding Usp proteins, which have been proposed to function as a molecular switch.
      Expression analyses revealed that AsD243 was transcribed in all plant organs, and
      progressively during all stages of nodulation. Its transcripts increased
      significantly at 7 days after inoculation, which is 2 days later than the onset
      of leghemoglobin expression in A. sinicus nodules. AsD243 was expressed more
      strongly in mature roots than in young roots regardless of inoculation status. We
      suggest that the AsD243 may have other functions in plant processes besides
      nodulation.

PMID- 16884823
TI  - Cloning of two isoforms of soluble acid invertase of Japanese pear and their
      expression during fruit development.
AB  - Soluble acid invertase (S-AIV; EC 3.2.1.26) in Japanese pear fruit has an
      important role in accumulating hexoses during fruit enlargement and regulates the
      sucrose-to-hexose ratio in the vacuole. Full-length cDNA of PsS-AIV1 and PsS-AIV2
      isoforms were cloned from Japanese pear fruit and their amino acid sequences
      share 40% identity; PsS-AIV1 was confirmed to code S-AIV isozyme purified
      previously. The roles of PsS-AIV1 and PsS-AIV2 genes throughout fruit development
      and in sugar composition were investigated by semi-quantitative reverse
      transcriptase-polymerase chain reaction (RT-PCR) analysis using specific primers
      of their transcripts. PsS-AIV1 transcript had a maximum level at 34 days after
      full bloom (DAFB) and decreased rapidly during fruit development; PsS-AIV2
      transcript increased gradually during fruit growth from 34 DAFB, had its maximum
      level at 79 DAFB and remained high until 107 DAFB at active fruit enlargement.
      The activity of S-AIV was highest at 34 DAFB, decreased during fruit growth until
      66 DAFB, remained almost the same during early fruit enlargement until 79 DAFB
      and then decreased again. Soluble sugars fructose and glucose began accumulating
      predominantly during fruit enlargement from 66 DAFB; sucrose began increasing
      rapidly during fruit maturation from 121 DAFB. High expression of PsS-AIV1
      transcript and high enzyme activity in the young fruit stage seems to have an
      important role in supplying a lot of substrate for energy needed for cell
      division and growth by hydrolyzing sucrose to hexoses. Increasing PsS-AIV2
      expression during fruit enlargement may lead to rapid cell expansion through
      increased osmotic pressure by accumulation of a large amount of hexose in the
      vacuole.

PMID- 16884824
TI  - Proteomic and genomic characterization of Kunitz trypsin inhibitors in wild and
      cultivated soybean genotypes.
AB  - In this study, we investigated protein and genetic profiles of Kunitz trypsin
      inhibitors (KTIs) in seeds of 16 different soybean genotypes that included four
      groups consisting of wild soybean (Glycine soja), the cultivated soybean (G. max)
      ancestors of modern N. American soybean cultivars (old), modern N. American
      soybean (elite), and Asian cultivated soybean landraces that were the immediate
      results of domestication from the wild soybean. Proteins were well separated by
      two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and stained protein
      cut from a 2D-PAGE indicated that KTI exists as multiple isoforms (spots) in
      soybean. Protein spots of KTI were identified and characterized using matrix
      assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF
      MS). Although overall distribution patterns of the KTI protein spots appeared
      similar, the number and intensity of the protein spots between wild and
      cultivated genotypes varied. Three KTI peptides were identified in three of the
      wild genotypes, PI 393551, PI 407027 and PI 407282, in which KTI3 peptide showed
      highest intensity. The remaining wild genotype, PI 366120, showed four protein
      spots. In contrast, the ancestors, modern and Asian landrace genotypes showed
      only two protein spots corresponding to KTI. On the basis of DNA blot analysis,
      there is one copy of the KTI3 gene in all 16 genotypes. Polymorphism was detected
      in one of the wild genotypes (PI 366120) both in proteomic and genomic analyses.
      Our data suggest that the major variation of protein profiles were between wild
      and cultivated soybean genotypes rather than among genotypes in the same group.
      Genetic variation of KTI1, KTI2 and KTI3-related genes were detected within and
      between groups.

PMID- 16884825
TI  - Activity and subcellular localization of glucose-6-phosphate dehydrogenase in
      peach fruits.
AB  - The subcellular distribution and activity of glucose-6-phosphate dehydrogenase
      (G6PDH, EC 1.1.1.49) were studied in developing peach (Prunus persica L. Batsch
      cv. Zaoyu) fruit. Fruit tissues were separated by differential centrifugation at
      15,000g into plastidic and cytosolic fractions. There was no serious loss of
      enzyme activity (or activation) during the preparation of fractions. G6PDH
      activity was found in both the plastidic and cytosolic compartments. Moreover,
      DTT had no effect on the plastidic G6PDH activities, that is, the redox
      regulatory mechanism did not play an important role in the peach fleshy tissue.
      Results from the immunogold electron-microscope localization revealed that G6PDH
      isoenzymes were mainly present in the cytosol, the secondary wall and plastids
      (chloroplasts and chromoplasts), but scarcely found in the starch granules or the
      cell wall. In addition to a decrease in fruit firmness, the G6PDH activity in the
      cytotolic and plastidic fractions increased, and anthocyanin started to
      accumulate during fruit maturation. These results suggest that G6PDH, by
      providing precursors for metabolic processes, might be associated with the red
      coloration that occurs in peach fruit.

PMID- 16884826
TI  - Does exogenous application of salicylic acid through the rooting medium modulate
      growth and photosynthetic capacity in two differently adapted spring wheat
      cultivars under salt stress?
AB  - In order to assess whether exogenous application of salicylic acid (SA) through
      the rooting medium could modulate the photosynthetic capacity of two wheat
      cultivars differing in salinity tolerance, a hydroponic experiment was conducted
      under greenhouse conditions. Seeds of a salt tolerant (S-24) and a moderately
      salt sensitive (MH-97) cultivar were germinated at 0 or 150 mM NaCl in Hoagland's
      nutrient solution containing different levels of salicylic acid (SA) (0, 0.25,
      0.50, 0.75 and 1.00 mM) for 7d. Seven-day old wheat seedlings were transferred to
      hydroponics and grown at 0, or 150 mM NaCl for for further 30 d. Different levels
      of salicylic acid (SA) were also maintained in the solution culture. After 30 d,
      four plants out of six were harvested and the remaining plants were left for the
      estimation of yield attributes Salt stress reduced the growth and grain yield of
      both cultivars. However, cv. S-24 performed better than MH-97 under salt stress
      with respect to leaf area, and grain yield. Exogenous application of SA promoted
      growth and yield, and counteracted the salt stress-induced growth inhibition of
      salt tolerant S-24, whereas for MH-97 there was no improvement in growth or grain
      yield with SA application. Of the varying SA levels used, the most effective
      levels for promoting growth and grain yield were 0.75 and 0.25 mM under normal
      and saline conditions, respectively. The improvement in growth and grain yield of
      S-24 due to SA application was associated with improved photosynthetic capacity.
      Changes in photosynthetic rate due to SA application were not due to stomatal
      limitations, but were associated with metabolic factors, other than
      photosynthetic pigments and leaf carotenoids.

PMID- 16884828
TI  - Allosteric modulation of [3H]EBOB binding to GABAA receptors by diflunisal
      analogues.
AB  - Allosteric modulatory effects of 12 biphenyl derivatives of diflunisal and two
      fenamates were studied on A-type receptors of GABA (GABAAR) via [3H]4'
      ethynylbicycloorthobenzoate (EBOB) binding to synaptic membrane preparations of
      rat forebrain. A simplified ternary allosteric model was used to determine
      binding affinities of the compounds and the extents of cooperativity with GABA.
      Structure activity analysis revealed that 4-hydroxy substituents of the biphenyls
      contribute to their micromolar binding affinities more than 3-carboxyl groups.
      Electron-withdrawing fluorinated substituents, especially in ortho position, were
      also advantageous. These factors also strongly enhanced the cooperativity with
      GABA binding. The correlation between displacing potency of the allosteric agents
      and cooperativity with GABA suggests that these processes are associated with
      common mechanisms. The pharmacological relevance of these interactions is
      discussed. These data help to differentiate the structural requirements of these
      agents to act on GABAergic neurotransmission versus nonsteroidal anti
      inflammatory effects.

PMID- 16884829
TI  - Quantitative structure activity relationship studies of aryl heterocycle-based
      thrombin inhibitors.
AB  - A quantitative structure activity relationship (QSAR) analysis has been performed
      on a data set of 42 aryl heterocycle-based thrombin inhibitors. Several types of
      descriptors including topological, spatial, thermodynamic, information content
      and E-state indices were used to derive a quantitative relationship between the
      anti thrombin activity and structural properties. Genetic algorithm based genetic
      function approximation method of variable selection was used to generate the
      model. Best model was developed when number of descriptors in the equation was
      set to five. Highly statistically significant model was obtained with atom type
      logP descriptors, logP and Shadow_YZ. The model is not only able to predict the
      activity of new compounds but also explained the important regions in the
      molecules in a quantitative manner.

PMID- 16884830
TI  - [Interest of an internist's consultation in uveitis. Comparative study in 66
      cases].
AB  - BACKGROUND: After exclusion of a masquerade syndrome, uveitis may be associated
      with infection, systemic diseases, specific ocular diseases, or may be drug
      induced. In order to improve diagnostic strategy in uveitis, we performed a
      comparative study to assess the importance of internist and ophtalmologist's
      collaboration and we proposed a well-adapted diagnostic procedure. MATERIAL AND
      METHODS: A comparative study was performed in a tertiary centre. The population
      was divided in two groups. The first one was retrospective and consisted of
      patients treated at the Ophthalmology department of Croix Rousse Hospital from
      1991 to 2002 without internist's collaboration. The second one was prospective
      and consisted of patients referred in the same centre in 2003 and 2004 with
      intervention of an internist. Patients of less than 18 years of age with pre
      existent diagnosis, specific ocular diseases, toxoplasmosis infection, or with
      human immunodeficiency virus infection were excluded. RESULTS: Sixty-six patients
      were included. Anterior uveitis was the most frequent form (25 cases), followed
      by panuveitis (20 cases), posterior uveitis (14) and intermediate uveitis (7).
      The most frequent cause of uveitis was systemic disease (19 cases) followed by
      infection (7 cases) and neurological entities (4 cases). The rate of diagnosis
      was 30.3% without internist's intervention and 60.6% when patients were referred
      to an internist (P=0,01). The internist intervention was contributive in 75% of
      diagnoses. CONCLUSIONS: The internist intervention significantly enhances the
      rate of etiological diagnoses in uveitis. These results should further strengthen
      the internist/ophthalmologist collaboration for patients with uveitis.

PMID- 16884831
TI  - [Acute pancreatitis revealing a systemic lupus erythematous].
AB  - INTRODUCTION: Acute pancreatitis is rarely seen in systemic lupus erythematous.
      CASE REPORT: A 28-year-old woman without significant past medical history, was
      hospitalized for sepsis and diagnosed with acute pancreatitis, which was found to
      be the initial presentation of a newly diagnosed systemic lupus erythematous.
      DISCUSSION: Acute pancreatitis as an initial presentation of systemic lupus
      erythematous is rare and is reported in only 10 cases in the literature. Multiple
      factors are involved in the pathogenesis. The role of corticosteroids in its
      apparition or resolution is still a subject of controversy.

PMID- 16884832
TI  - Receiver-operating characteristic analyses of body mass index, waist
      circumference and waist-to-hip ratio for obesity: Screening in young adults in
      central south of China.
AB  - BACKGROUND & AIMS: Recent data suggest that current obesity diagnostic criterion
      based on body mass index (BMI) above 30 in Caucasians may not be appropriate for
      Asian populations. Our aim was to identify the usefulness of BMI, waist
      circumference (WC) and waist-to-hip ratio (WHR) in screening for obesity in an
      Asian population. METHODS: A cross-sectional sample of 1109 males and 879 females
      aged 20-45-yr were recruited. Height, weight, WC, hip circumference and
      percentage body fat (PBF) were measured in all subjects. Then receiver-operating
      characteristic analyses were used to evaluate the performances of the three
      anthropometric indices. RESULTS: BMI, WC and WHR showed strong positive
      correlation with PBF (r=0.47-0.75) in both males and females within both age
      groups. True-positive rates ranged from 82.4% to 94.1% and 68.8% to 86.3% in
      males and females, respectively. True-negative rates ranged from 64.1% to 84.7%
      and from 56.9% to 79.0%, respectively. The areas under the curves (AUCs) for WC
      and BMI were high (0.76-0.92) in both sexes and divided age groups (20-30-yr and
      31-45-yr), and those for WHR were a little lower (0.74-0.88). CONCLUSIONS: BMI
      and WC are two important predictors for obesity in Chinese, and WHR is an
      alternative.

PMID- 16884833
TI  - Humoral response to hepatitis B vaccination and its relationship with T CD45RA+
      (naive) and CD45RO+ (memory) subsets in HIV-1-infected subjects.
AB  - HIV disease leads to defects in cell-mediated immunity, impairing the immune
      response to new and recall antigens. We studied 55 HIV 1-infected patients who
      received of recombinant DNA hepatitis B vaccine and 20 controls. The overall
      hepatitis B virus (HBV) seroconversion rate was 59%. The median CD4+ T cell count
      among responders was 452 cell/mm(3), higher than non-responders (359
      cells/mm(3)). The HIV plasmaviral loads were higher in non-responders. We
      concluded that total T CD4 cell count, memory T CD4+ cells and lower plasma viral
      load among HIV-1-infected subjects treated with HAART could be used to predict
      the immune response to vaccination with hepatitis B vaccine. Thus, considering
      cost benefits, HVB vaccination should be preferentially provided to HIV-infected
      patients with T CD4 cells count over 450 cells/mm(3), preferentially whose under
      HIV replication controlled.

PMID- 16884834
TI  - Expression of human immunodeficiency virus type 1 tat from a replication
      deficient herpes simplex type 1 vector induces antigen-specific T cell responses.
AB  - Herpes simplex type-1 virus (HSV-1) based vectors have been widely used in
      different gene therapy approaches and also as experimental vaccines against HSV-1
      infection. Recent advances in the HSV-1 technology do support the use of
      replication defective HSV-1 as vaccine vectors for delivery of foreign antigens.
      We have examined the ability of a recombinant replication-defective HSV-1 vector
      expressing the HIV-1 Tat protein to induce long-term Tat-specific immune
      responses in the Balb/c murine model. The results showed that vector
      administration by the subcutaneous route elicits anti-Tat specific T-cell
      mediated immune responses in mice characterized by the presence of the Tat
      specific cytotoxic activity and production of high levels of IFN-gamma.

PMID- 16884835
TI  - Mumps vaccine virus strains and aseptic meningitis.
AB  - Mumps immunization can easily be included in national schedules, particularly if
      combined with measles or measles and rubella vaccines, but debate continues
      concerning the relative safety of various licensed mumps vaccine strains. The
      opportunities for control of mumps are also being affected by differences in the
      cost of the vaccines prepared with different strains of mumps virus. The present
      report evaluates available data on the association of the Urabe and other strains
      of mumps vaccine with the occurrence of aseptic meningitis. We also review the
      comparative immunogenicity and efficacies of the most widely used mumps vaccines
      in controlled clinical trials and field evaluations, and briefly examine relative
      cost as it relates to the implementation of national immunization programs. We
      conclude that extensive experience with the most widely used mumps vaccine
      strains in many countries has shown that the risk-benefit ratio of live mumps
      vaccines is highly favourable for vaccination, despite the occasional occurence
      of aseptic meningitis.

PMID- 16884836
TI  - A controlled clinical trial comparing the safety and immunogenicity of a new
      adjuvanted hepatitis B vaccine with a standard hepatitis B vaccine.
AB  - A randomised trial was conducted in 285 adults not immune to hepatitis B (HB) to
      compare the safety and immunogenicity of a commercial aluminium-adjuvanted HB
      vaccine with and without an additional new adjuvant (AgB/RC-210-04 or AgB study
      groups, respectively). The additional adjuvant RC-529 is a fully synthetic
      monosaccharide mimetic of monophosphoryl lipid A. Subjects in the AgB/RC-210-04
      (n=136) and AgB (n=149) groups were vaccinated intramuscularly on days 0, 30, and
      180, according to the standard vaccination schedule for hepatitis B vaccines.
      Serum levels of anti-HBs were measured on days 30, 60, 90, 180, and 210. Standard
      safety assessments were made throughout the study period. The rates of
      seroprotection (anti-HBs > or =10.0 mIU/ml) were significantly greater for the
      AgB/RC-210-04 group at all time points: at day 90, the seroprotection rate, the
      primary endpoint of the trial, was 99% for AgB/RC-210-04 compared with 84% for
      AgB (p<0.0001). Similarly, geometric mean anti-HBs titres were significantly
      higher at all time points for the AgB/RC-210-04 group. There were more local
      reactions in the AgB/RC-210-04 group, however they were transient and this double
      adjuvanted formulation was well tolerated. We conclude that the addition of a
      synthetic adjuvant to the AgB vaccine significantly enhanced the immunogenicity
      of the commercial vaccine AgB. The results indicate furthermore that a two-dose
      regime of the double-adjuvanted vaccine (schedule: 0-1 month) may be sufficient
      to achieve seroprotection in nearly 100% of individuals.

PMID- 16884837
TI  - Analysis of the young and elderly variable gene repertoire in response to
      pneumococcal polysaccharides using a reconstituted SCID mouse model.
AB  - Significant changes in anti-pneumococcal polysaccharide (PPS) variable gene usage
      occur with aging and may be influenced by changes in cytokine environment. Severe
      combined immunodeficient (SCID) mice were engrafted with B cells obtained from
      young and elderly donors, supplemented with human cytokines and immunized with
      the pneumococcal polysaccharide vaccine. B cells specific for PPS serotypes 4 and
      14 were isolated from mice and immunized donors, and variable region sequences
      analyzed. Significant differences in variable heavy and light chain gene usage
      were observed between young and elderly adults despite a more constant cytokine
      environment. Due to the limitations of the hu-PBL-SCID model, the use of
      alternative systems would be beneficial in the elucidation of mechanisms
      underlying the reduced vaccine efficacy in the elderly.

PMID- 16884838
TI  - CNS prophylaxis in lymphoma: who to target and what therapy to use.
AB  - The purpose of this article is to review the current data on the risk of CNS
      relapse in patients with lymphoma and the efficacy of CNS directed prophylactic
      therapy. CNS relapse occurred in 30-50% of those with Burkitt lymphoma and acute
      lymphoblastic leukaemia/lymphoma prior to the introduction of intensified
      regimens that include CNS prophylaxis. Most patients with AIDS-related-lymphoma
      receive a short course of intrathecal prophylaxis but a re-evaluation of type and
      targeting of CNS prophylaxis is needed. Patients with diffuse large B-cell
      lymphoma (DLBCL) have a 5% overall risk of CNS relapse but a high risk sub
      population can be identified on the basis of raised LDH and >1 extranodal site,
      testicular or primary breast involvement. CNS prophylaxis for selected patients
      with DLBCL may be justified by risk but its benefit is not yet proven.
      Intravenous methotrexate > or = 3 g/m(2) achieves therapeutic levels in CSF and
      parenchyma and in combination with intrathecal methotrexate would be a reasonable
      option for prophylaxis.

PMID- 16884839
TI  - Risk and safety assessment on the consumption of Licorice root (Glycyrrhiza sp.),
      its extract and powder as a food ingredient, with emphasis on the pharmacology
      and toxicology of glycyrrhizin.
AB  - Licorice (or 'liquorice') is a plant of ancient origin and steeped in history.
      Licorice extracts and its principle component, glycyrrhizin, have extensive use
      in foods, tobacco and in both traditional and herbal medicine. As a result, there
      is a high level of use of licorice and glycyrrhizin in the US with an estimated
      consumption of 0.027-3.6 mg glycyrrhizin/kg/day. Both products have been approved
      for use in foods by most national and supranational regulatory agencies.
      Biochemical studies indicate that glycyrrhizinates inhibit 11beta-hydroxysteroid
      dehydrogenase, the enzyme responsible for inactivating cortisol. As a result, the
      continuous, high level exposure to glycyrrhizin compounds can produce
      hypermineralocorticoid-like effects in both animals and humans. These effects are
      reversible upon withdrawal of licorice or glycyrrhizin. Other in vivo and
      clinical studies have reported beneficial effects of both licorice and
      glycyrrhizin consumption including anti-ulcer, anti-viral, and hepatoprotective
      responses. Various genotoxic studies have indicated that glycyrrhizin is neither
      teratogenic nor mutagenic, and may possess anti-genotoxic properties under
      certain conditions. The pharmacokinetics of glycyrrhizin have been described and
      show that its bioavailability is reduced when consumed as licorice; this has
      hampered attempts to establish clear dose-effect levels in animals and humans.
      Based on the in vivo and clinical evidence, we propose an acceptable daily intake
      of 0.015-0.229 mg glycyrrhizin/kg body weight/day.

PMID- 16884840
TI  - Gender differences in health-related quality of life among the elderly: the role
      of objective functional capacity and chronic conditions.
AB  - Although worse Health-Related Quality of Life (HRQL) among women has been widely
      described, it remains unclear whether this is due to differential reporting
      patterns, or whether there is a real difference in health status. The objective
      of this study was to evaluate to what extent gender differences in HRQL among the
      elderly might be explained by differences in performance-based functional
      capacity and chronic conditions, using the conceptual model of health outcomes as
      proposed by Wilson and Cleary. Data are from a cross-sectional home survey of 872
      surviving individuals from an elderly cohort representative of Barcelona's
      general population. Complete valid data for these analyses were obtained from 62%
      of the subjects (n = 544). The evaluation included the Nottingham Health Profile
      (NHP), a generic measure of HRQL; three performance-based functional capacity
      tests (balance, chair-stand, and walking tests); and a standardized list of self
      reported chronic conditions. A series of multiple linear regression models were
      built with the total NHP score as the dependent variable, with gender, socio
      demographic information, performance-based functional capacity and chronic
      conditions included sequentially, as independent variables. Women (65.4%) showed
      worse results than men on HRQL (mean of NHP total score 28.3 vs 16.7, p < 0.001)
      and functional capacity (mean of summary score 7.1 vs 8.3, p < 0.001). Functional
      capacity, arthritis, back pain, diabetes, and depression were significantly
      associated to the NHP total score in the final regression model, which explained
      42% of the variance. Raw differences by gender in the total NHP score were 11.5
      points (p < 0.001), but decreased to a non-significant 3.2 points (p = 0.18)
      after adjusting for all the other variables. In conclusion, our data suggest that
      worse reported HRQL in elderly women is mainly due to a higher prevalence of
      disability and chronic conditions.

PMID- 16884841
TI  - Nursing in Bangladesh: rhetoric and reality.
AB  - In the past decade concern has been raised through independent channels that
      nurses in Bangladesh do not provide active hands on care directly to patients as
      envisioned when the British nursing model was first introduced decades ago. The
      objective of the study was to observe the activities nurses engaged in during
      their working hours on major medical and surgical wards. A total of 24,587 min of
      nursing activities were recorded by three observers in 18 hospitals between the
      hours of 05.00 and 23.00 h over a 3 month period. These were compared with
      reports of the nurses about their activities, and indirectly with the activities
      outlined in the nursing curriculum. Nurses in government hospitals spent only
      5.3% of their working time in direct contact with their patients. Paperwork and
      indirect patient care occupied nurses for 32.4% of their time while 50.1% fell
      under the category of unproductive time such as time away from the ward and
      chatting with other nurses. Hospital support workers and patients' relatives
      acted as nurse surrogates. When asked how they spent their day, nurses reported
      what the curriculum specifies but not what was observed. As a consequence policy
      decisions have not consistently reflected this reality. By contrast, nurses in
      the hospitals outside the government system were found to spend 22.7% directly
      with patients. A deeper understanding of nurse's behaviour on the wards is
      required to determine the desired role of the nurse that will, in turn, feed into
      nursing policy and decisions related to resource allocation.

PMID- 16884842
TI  - Dim light melatonin onset (DLMO): a tool for the analysis of circadian phase in
      human sleep and chronobiological disorders.
AB  - The circadian rhythm of melatonin in saliva or plasma, or of the melatonin
      metabolite 6-sulphatoxymelatonin (aMT6S) in urine, is a defining feature of
      suprachiasmatic nucleus (SCN) function, the endogenous oscillatory pacemaker. A
      substantial number of studies have shown that, within this rhythmic profile, the
      onset of melatonin secretion under dim light conditions (the dim light melatonin
      onset or DLMO) is the single most accurate marker for assessing the circadian
      pacemaker. Additionally, melatonin onset has been used clinically to evaluate
      problems related to the onset or offset of sleep. DLMO is useful for determining
      whether an individual is entrained (synchronized) to a 24-h light/dark (LD) cycle
      or is in a free-running state. DLMO is also useful for assessing phase delays or
      advances of rhythms in entrained individuals. Additionally, it has become an
      important tool for psychiatric diagnosis, its use being recommended for phase
      typing in patients suffering from sleep and mood disorders. More recently, DLMO
      has also been used to assess the chronobiological features of seasonal affective
      disorder (SAD). DLMO marker is also useful for identifying optimal application
      times for therapies such as bright light or exogenous melatonin treatment.

PMID- 16884843
TI  - Trends in obstetric interventions in the Dutch obstetrical care system in the
      period 1993-2002.
AB  - OBJECTIVE: To determine trends in induction of labour-, instrumental vaginal
      delivery- and caesarean section rates in the Netherlands in the period 1993-2002.
      STUDY DESIGN: Data derived from The Netherlands Perinatal Registry and Statistics
      Netherlands were used to calculate annual rates for induction of labour,
      instrumental vaginal delivery and caesarean section. Regarding caesarean section,
      rates were also calculated for different subgroups with respect to parity,
      presentation of the fetus, gestational age and multiple pregnancies. In the
      subgroup of women with a singleton fetus in vertex presentation between 37 and 42
      weeks of gestation instrumental delivery rates were compared for women with
      induced labours and women in spontaneous labour. RESULTS: The overall CS rate
      rose from 8.1 to 13.6%. Proportionally the rise was greatest for breech
      presentation (+37.7%), multiple gestations (+12.7%) and women delivering between
      24 and 28 weeks (+9.5%). However, in absolute numbers the rise was most
      impressive in the group of women with a singleton fetus in vertex presentation
      between 37 and 42 weeks of gestation. Rate of induction of labour and
      instrumental vaginal delivery remained constant (approximately 15% respectively
      10% of all deliveries). In nulliparous term women with singletons in vertex
      presentation the CS rate increased with 8.0% to a rate of 20.7% when labour was
      induced versus an increase of 3.4% to a rate of 7.5% in spontaneous labour.
      CONCLUSION: In absolute numbers the rise in CS was most extensive in the group of
      women with a singleton fetus in vertex presentation between 37 and 42 weeks of
      gestation. Induction of labour rates and instrumental vaginal delivery rates
      remained constant during the past decade.

PMID- 16884844
TI  - Results of double-blind placebo-controlled crossover study of sildenafil citrate
      (Viagra) in women suffering from obstructed voiding or retention associated with
      the primary disorder of sphincter relaxation (Fowler's Syndrome).
AB  - OBJECTIVES: Women with the primary disorder of sphincter relaxation find voiding
      difficult. Studies have identified neuronal nitric oxide synthase in the female
      urethral sphincter, and nitric oxide donors have been shown to decrease sphincter
      pressures. The aim of our study was to determine if sildenafil could improve
      sphincter relaxation and thereby increase flow rates and improve bladder
      emptying. METHODS: Twenty women with complete (5), partial retention or
      obstructed voiding (15) with a maximum flow rate (Qmax) of less than 15 ml/min
      with an elevated maximal urethral closure pressure (92--age cm H(2)O) and
      sphincter volume (>1.6 cm(3)) were included in the study. The study was a double
      blind, randomised, placebo-control, crossover design, with patients taking
      sildenafil or placebo, and with measurement of flow rate and residual volume at
      baseline and after each treatment phase. Voiding diary, quality of life, and
      International Prostate Symptom Score (IPSS) data were also collected. RESULTS: No
      statistical significant difference was seen in any voiding parameters and diaries
      when sildenafil citrate was compared with placebo. There was a significant mean
      decrease in IPSS of 3.64 between baseline and the sildenafil phase (p=0.0083),
      but not when compared with placebo. In the subgroup of women with partial
      retention and obstructed voiding (15/20), there was a statistically significant
      increase in Qmax of 4.7 ml/sec (p=0.025) between sildenafil and baseline; however
      this difference was not seen when compared with placebo. CONCLUSIONS: This is the
      first study looking at sildenafil in voiding dysfunction in women. Clinical
      improvements with sildenafil were not significant when compared with placebo.
      Sildenafil was not effective as a therapeutic pharmacologic agent in this group
      of patients.

PMID- 16884845
TI  - In situ stabilisation/solidification: project lifecycle.
AB  - The successful application of any remedial technology, including
      stabilisation/solidification, begins with the site investigation. Following a
      review of the data collected during the site investigation, a treatability study
      (TS) and pilot study (PS) are prerequisites to full-scale implementation as they
      show the effects and delivery of binders to the soils, the geochemistry of the
      soils, and binder dosages necessary for the existing geology. Further, evaluating
      the data gathered during the TS and PS can help in accurately estimating and
      executing full-scale operations. Invariably, deviations from the TS and PS
      regarding soil characteristics and soil chemistry may exist, but the experience
      gained via the TS and PS aids in making decisions when faced with new and
      unexpected conditions in the field. This paper will discuss the execution of
      typical TS and PS applications and their implementation for full-scale treatment.
      Because the long-term performance durability of design mixes and technology
      applications are not generally addressed in remediation, post-remediation
      monitoring and sampling data must be made available to the public to advance the
      science and art of stabilisation/solidification. As a first step in advancing
      this technology, this paper follows the lifecycle of stabilisation/
      solidification projects from the site investigation through the completion of
      full-scale work. A 10-year post-remediation sampling event also evidences the
      long-term viability of the technology.

PMID- 16884846
TI  - Mining the past.
AB  - Whenever we hear of an accident elsewhere we are eager to learn what happened and
      what recommendations have been made to prevent it happening again. However, we
      can learn as much from past accidents that have been forgotten or were never
      widely reported. Some such accidents are described, including entry to confined
      spaces, the collapse of a gasholder and the collapse of a tank for an unusual
      reason.

PMID- 16884847
TI  - Co-digestion of mixed industrial sludge with municipal solid wastes in anaerobic
      simulated landfilling bioreactors.
AB  - In this study, the feasibility of the anaerobic co-digestion of a mixed
      industrial sludge with municipal solid wastes (MSW) was investigated in three
      simulated anaerobic landfilling bioreactors during a 150-day period. All of the
      reactors were operated with leachate recirculation. One of them was loaded only
      with MSW (control reactor); the second reactor was loaded with mixed industrial
      sludge and MSW, the weight ratio of the MSW to mixed industrial sludge was 1:1
      (based on dry solid) (Run 1); the third reactor was loaded with mixed industrial
      sludge and MSW, the weight ratio of the MSW to mixed industrial sludge was 1:2
      (based on dry solid) (Run 2). The VFA concentrations decreased significantly in
      Run 1 and Run 2 reactors at the end of 150 days. The pH values were higher in Run
      1 and Run 2 reactors compared to control reactor. The differences between
      leachate characteristics, the biodegradation and the bioefficiency of the
      reactors were compared. The NH(4)-N concentrations released to leachate from
      mixed sludge in Run 1 and Run 2 reactors were lower than that of control reactor.
      The BOD(5)/COD ratios in Run 1 and Run 2 reactors were lower than that of control
      reactor at the end of 150 days. Cumulative methane gas productions and methane
      percentages were higher in Run 1 and Run 2 reactors. Reductions in waste
      quantity, carbon percentage and settlement of the waste were better in Run 1 and
      Run 2 reactors compared to control reactor at the end of 150 days. Furthermore,
      TN and TP removals in waste were higher in reactors containing industrial sludge
      compared to control. The toxicity test results showed that toxicity was observed
      in reactors containing industrial mixed sludge.

PMID- 16884848
TI  - Oxidation treatment of diesel soot particulate on CexZr1-xO2.
AB  - Catalytic oxidation of diesel soot particulate on Ce(x)Zr(1-x)O(2) catalysts was
      investigated. Results indicated that Ce/Zr ratios had a significant influence on
      the catalytic activities. Compared with the ignition temperature (T(i)) of
      uncatalyzed soot combustion, T(i) of Ce(0.5)Zr(0.5)O(2) with the best catalytic
      behavior decreased by 80 degrees C. The reactant gas compositions (O(2), H(2)O
      and NO) affected the catalytic activities too. O(2)-TPD, TG-DTA and XPS
      characterization results showed that Ce(x)Zr(1-x)O(2) released lattice oxygen
      continuously to promote the soot combustion even no gas oxygen occurred in the
      reaction atmosphere. The mechanisms of spill-over and reduction/oxidation
      functioned synergistically for soot catalytic combustion.

PMID- 16884849
TI  - Infection by ME7 prion is not modified in transgenic mice expressing the yeast
      chaperone Hsp104 in neurons.
AB  - The Hsp104 chaperone induces thermo-tolerance in yeast and rescues proteins
      trapped in aggregates. In this study, we showed that xenogenic expression of
      Hsp104 dramatically increased the viability of the neuronal mouse CAD cell line
      after exposure to heat shock. These results indicate that the Hsp104 protein
      confers thermo-resistance to mammalian neuronal cells, the canonical property of
      Hsp104 in yeast. Hsp104 also determines the prion state of prion-like proteins in
      yeast and to investigate whether Hsp104 expression may modify mammalian prion
      infection in vivo, transgenic mice with specific expression of Hsp104 in neurons
      were generated. Mice develop and reproduce normally, they show no detectable
      physical defect and may constitute valuable model for the study of aggregation
      prone neuropathological disorders. Hsp104 transgenic and control littermates were
      infected intracerebrally with the ME7 strain of scrapie. No differences in the
      incubation time of the disease or in PrP(Sc) accumulation were observed between
      transgenic and control mice. These results suggest that the heat-shock protein
      Hsp104 is not efficient to modulate the multiplication of mammalian prions and/or
      to counteract neurodegeneration in the brain of scrapie-infected mice.

PMID- 16884851
TI  - Deltamethrin-impregnated collars for the control of canine leishmaniasis:
      evaluation of the protective effect and influence on the clinical outcome of
      Leishmania infection in kennelled stray dogs.
AB  - A 2-year field study on kennelled stray dogs living in a highly endemic area of
      leishmaniasis was designed to evaluate whether deltamethrin-impregnated collars
      (Scalibor) Protector Band) could confer protection against leishmaniasis in this
      peculiar setting, and to assess differences in clinical outcomes between collared
      and uncollared dogs. A cohort of 120 clinically healthy and Leishmania
      seronegative dogs was enrolled, 50% of which were collared before the 2003
      transmission season, and then re-collared before the subsequent season. Collared
      and uncollared animals were allowed to live with infected dogs in same groups
      within the kennel. Follow-up included serological (IFAT) assessment twice a year
      with parasitological Leishmania confirmation, and clinical evaluation performed
      every 3 months on seroconverted dogs from both groups. Collar losses during the
      two seasons were high (35%). About 50% of enrolled dogs were lost at follow-up
      because of death or they were moved to other locations. After the 2003 season,
      cross-sectional serological examinations tested positive in 5 out of 44 collared
      animals (11.4%) and in 14 out of 34 controls (41.2%), with 72.3% estimated
      protection (P<0.005). After the 2004 season, 7/31 seronegative collared dogs
      seroconverted (22.6%) compared with 7/17 seronegative controls (41.2%), with
      45.1% protection (P=0.15). At the end of the study, the cumulative rate of
      protection was 50.8% (P=0.005). At the clinical evaluation of 21 seroconverted
      dogs from both groups, canine leishmaniasis signs were significantly more
      frequent (90% versus 36%, P=0.017) and rapidly progressive in uncollared than in
      collared dogs. Reasons for such partial clinical protection in collared dogs may
      be found in the vector anti-feeding effect of protector bands, resulting in a
      lower number of infectious bites and, probably, in the reduction of antigenic
      stimuli necessary to shift toward a non-protective immune response.

PMID- 16884850
TI  - Peripheral neuropathy and object length perception by effortful (dynamic) touch:
      a case study.
AB  - The spatial extents of hand-held objects can be perceived nonvisually by wielding
      them. This ability of effortful or dynamic touch to exploit the mass moments of
      an object to perceive its length was evaluated with a 40-years old right-handed
      woman with surgically treated Arnold-Chiari Type 1 Malformation and cervical
      syrinx. At the time of the experiment she presented with loss of discriminative
      touch in the left arm but no comparable sensory deficits in the right arm or the
      lower extremities. She could neither identify objects in her left hand nor tell
      that they were in the hand while manipulating them. She could, however, grasp an
      object tightly and wield it on request. In the experiment she wielded weighted
      rods of 45, 60, and 80cm length about the wrist. There were two main results.
      First, her nonvisual perception of rod length by the insensate left arm scaled
      systematically with rod moment of inertia. The scaling matched that of the intact
      right arm and the nondominant arm of haptically unimpaired controls tested with
      rods of similar dimensions. Second, her right arm was superior in accuracy and
      reliability than her insensate left arm and was equal to or better than the
      dominant arm of the control group on key measures of nonvisual length perception.
      The first result was evaluated in respect to the notions of numb touch and
      differences in the neural bases of discriminative and effortful touch. The second
      result was discussed in terms of contralateral cortical enhancement by
      deafferentation.

PMID- 16884852
TI  - Comparison of Neospora caninum distribution, parasite loads and lesions between
      epidemic and endemic bovine abortion cases.
AB  - It has been suggested that the abortion herd pattern could influence bovine
      foetal neosporosis. Here, a comparison of (i) Neospora caninum DNA-detectability
      by PCR, (ii) N. caninum-associated lesions and (iii) parasite loads in target
      organs was made between epidemic and endemic abortion cases. We observed that N.
      caninum DNA was predominantly detected in more than one organ in the foetuses
      from herds with epizootic rather than endemic abortion cases (P<0.05, Fisher F
      test). The highest parasite burdens were found in the heart in foetuses from
      outbreaks of epidemic abortion and in the brain in endemic cases (P<0.05, Kruskal
      Wallis H-test). Moreover, foetuses from epidemic outbreaks had significantly
      higher parasite burdens in heart (P<0.05, Mann-Whitney U-test) than endemic
      abortion cases. Epidemic abortion cases showed higher lesion frequencies in liver
      (P<0.05, Fisher F-test). This report confirms that the abortion herd pattern is
      an important factor that influences pathogenesis in natural N. caninum
      infections.

PMID- 16884853
TI  - Cross-transmission studies with Hypoderma lineatum de Vill. (Diptera: Oestridae):
      attempted infestation of goats (Capra hircus).
AB  - The potential for cross-transmission of Hypoderma lineatum from cattle to
      domestic goats (Capra hircus) was examined using artificial infestation
      techniques. Two routes of infestation, subcutaneous injection and dermal
      penetration, were used to expose goats to newly hatched first instars. Presence
      of antibodies and appearance of circulating antigen (hypodermin C) were evaluated
      at selected intervals for up to 40 weeks post-infestation. In addition,
      immunoblots against H. lineatum first-instar proteins were conducted using sera
      taken at 10 weeks post-infestation. Goats were palpated for the presence of
      developing larvae at sub-dermal sites beginning at week 30 pi. No developing
      larvae were palpated at any time, regardless of the route of infestation nor was
      circulating antigen detected in any infested goats. Antibodies were present at
      weeks 6 and 10 and week 27 pi in both infested groups. Immunoblots indicated all
      infested goats produced antibodies to first instar H. lineatum antigens. H.
      lineatum appears to be incapable of completing development in domestic goats
      although the transient appearance of ELISA detectable antibodies and the presence
      of bands on immunoblots suggests that at least some larvae survive long-enough to
      engender a humoural response. The host specificity of H. lineatum is discussed in
      light of the general concepts of host-parasite relationships of oestrids.

PMID- 16884854
TI  - Study of burn deaths in Nagpur, Central India.
AB  - A series of 384 victims of burn deaths were reviewed to determine the trends of
      burn deaths in Nagpur, an urban area of Central India. It was found that deaths
      due to burning accounted for 21.6% of the total medicolegal deaths. Female
      (74.2%) predominance was seen in burning with male-female ratio equal to 1:2.9.
      Most of the victims of burn deaths were between 11-40 years with peak at 21-30
      years (47.1%). Married (79.9%) outnumbered unmarried ones in burning. Accidental
      burning (75%) was the commonest manner of burn deaths followed by suicidal and
      homicidal burning. Kerosene was the main causative factor for burning with
      kerosene burner as the commonest causative agent. The kitchen (69.3%) was the
      commonest place of burning and clothes of the body, particularly the sari as the
      commonest vehicle of burns.

PMID- 16884856
TI  - A porcine deep dermal partial thickness burn model with hypertrophic scarring.
AB  - We developed a reproducible model of deep dermal partial thickness burn injury in
      juvenile Large White pigs. The contact burn is created using water at 92 degrees
      C for 15s in a bottle with the bottom replaced with plastic wrap. The depth of
      injury was determined by a histopathologist who examined tissue sections 2 and 6
      days after injury in a blinded manner. Upon creation, the circular wound area
      developed white eschar and a hyperaemic zone around the wound border. Animals
      were kept for 6 weeks or 99 days to examine the wound healing process. The wounds
      took between 3 and 5 weeks for complete re-epithelialisation. Most wounds
      developed contracted, purple, hypertrophic scars. On measurement, the thickness
      of the burned skin was approximately 1.8 times that of the control skin at week 6
      and approximately 2.2 times thicker than control skin at 99 days after injury. We
      have developed various methods to assess healing wounds, including digital
      photographic analysis, depth of organising granulation tissue,
      immunohistochemistry, electron microscopy and tensiometry. Immunohistochemistry
      and electron microscopy showed that our porcine hypertrophic scar appears similar
      to human hypertrophic scarring. The development of this model allows us to test
      and compare different treatments on burn wounds.

PMID- 16884855
TI  - Microalbuminuria: a marker of endothelial dysfunction in thermal injury.
AB  - INTRODUCTION: Systemic endothelial dysfunction (SED) and capillary leak occur
      following severe burn. SED can be assessed as low-level albuminuria
      (microalbuminuria) detectable only by sensitive immunoassay. This study compared
      the magnitude and duration of microalbuminuria with burn surface area and
      associated aggravating factors. METHODS: Serial urine specimens were collected
      from 2 to 36 h after injury from 43 adult burn patients with a mean total body
      surface area (TBSA) of 32% (range 15-68%) and during 44 episodes of wound
      manipulation within the same period. Urinary albumin was expressed as the
      albumin/creatinine ratio (ACR, normal <2.3 mg/mmol). RESULTS: Median ACR was
      highest 2h after injury (12.3 range 1.8-118 mg/mmol) returning to normal within 6
      h. Full thickness burns (mean 17%) showed a significant association with ACR
      between 3 and 7h after burn. ACR was higher for up to 8 h in the presence of
      inhalation injury, alcohol intoxication or accelerant (p<0.05). ACR rose within
      30 min of escharotomy or wound scrubbing (p<0.01). CONCLUSION: Severe burn
      produces variable SED which recurs with wound manipulation. Inhalation injury,
      alcohol intoxication and accelerant all showed a stronger association with SED
      than TBSA. Microalbuminuria provides a means of monitoring microvascular
      integrity during the early after injury period.

PMID- 16884857
TI  - Commentary: Evidence-based principles applied to the management of colorectal
      cancer.

PMID- 16884858
TI  - Spindle cell oncocytoma of the adenohypophysis: report of a case with a 16-year
      follow-up.
AB  - Spindle cell oncocytoma (SCO) is a recently described, rare neoplasm of the
      anterior pituitary. Clinically and radiologically simulating a non-functioning
      macroadenoma, its eponymous fusiform cells display a non-epithelial phenotype
      with conspicuous cytoplasmic accumulation of mitochondria. We report a case of
      SCO retrospectively identified in a biopsy specimen 16 years after
      transsphenoidal operation of a 48-year-old woman. Presenting symptoms were
      adynamia and transient decrease of visual acuity. Neuroimaging showed an
      isointense, enhancing, sellar-centered mass 1.8 cm in diameter without evidence
      of invasive growth. No postoperative adjuvant therapy was administered. The
      patient was left with panhypopituitarism, yet no recurrence was seen during
      follow-up. Initially diagnosed as a null cell adenoma of oncocytic type, repeat
      immunohistochemistry showed the characteristic coexpression of S100 protein,
      vimentin, and epithelial membrane antigen. Oncocytic granula stained intensely
      with antimitochondrial antibody 113-1, and were negative with the lysosomal
      marker CD68. Anterior pituitary hormones tested negative, and there was no
      evidence of neuroendocrine differentiation using antibodies to synaptophysin and
      chromogranin. Few cells stained for glial fibrillary acidic protein (GFAP). SCO
      has been proposed to represent a neoplasm of folliculo-stellate cells (FSCs).
      While the dynamic properties of the latter are incompletely characterized, and
      indeed no specific marker allows for their identification, overlapping features
      of SCO with look alikes, in particular pituicytoma, point to FSCs being a
      potential adult stem cell. The favorable outcome of the present case further
      argues for SCO to be considered a low-grade neoplasm. Moderate tumor size, lack
      of invasiveness, and low proliferation rate are likely predictors of benign
      behavior.

PMID- 16884859
TI  - Antiinflammatory activity and acute toxicity of Dodonaea viscosa.
AB  - The hydroalcoholic extract (HAE) of the leaves of Dodonaea viscosa, given by oral
      route at dose of 300 mg/kg, significantly inhibited the paw edema induced by
      carrageenin injection. The extract did not show any sign of toxicity in mice up
      to 5000 mg/kg p.o. This result seems to support the use of D. viscosa leaves
      ethanolic extract in relieving inflammation.

PMID- 16884860
TI  - Neurophysiologic effects at low level 1.8 GHz radiofrequency field exposure: a
      multiparametric approach on freely moving rats.
AB  - Deleterious effects on healthcare and particularly disruption of the cholinergic
      system have been reported after exposure to radiofrequency field at low power
      density. This work presents a 72 hours multiparametric study, where cholinergic
      system was investigated using a neurochemical, electrophysiological and
      physiological approaches. Free moving rats were exposed 24 hours to RF GSM signal
      at 1.8 GHz at low power density (1.2 and 9 W/m(2)). Acetylcholine (ACh) release
      in the hippocampus was simultaneously monitored using the microdialysis
      technique, electroencephalogram (EEG), electromyogram (EMG) and subcutaneous
      temperature. A spectral analysis of EEG was also performed and sleep stages were
      determined. After experimental time, the animals were sacrificed and a NMR study
      was performed on lipid brain extract. No significant parameters modification was
      observed under RF exposure. The only significant difference was the lack of
      increase in time spent in REM sleep, the third day, for the 1.2 W/m(2) group.
      This observation appeared difficult to explain and could not be reasonably
      related with RF exposure. Similarly, the NMR study also failed to show any effect
      of RF.

PMID- 16884861
TI  - Biological cost of fluoroquinolone resistance in Escherichia coli implicated in
      polyclonal infection.
AB  - Polyclonal Escherichia coli strains were isolated in a transplanted patient who
      experienced successive septic shocks. Fluoroquinolone susceptible and resistant
      strains were corresponding to different PFGE fragment profiles. The gyrA S83L
      mutation was associated with a reduction in biological fitness. Resistant strain
      was selected by a long-term single use of ofloxacin.

PMID- 16884862
TI  - [Molecular analysis of Paget's disease of bone].

PMID- 16884863
TI  - LRRK2: a link between familial and sporadic Parkinson's disease?

PMID- 16884864
TI  - Why do dolphins jump? Interpreting the behavioural repertoire of bottlenose
      dolphins (Tursiops sp.) in Doubtful Sound, New Zealand.
AB  - Only a limited number of studies have tried to determine the purpose of surface
      behavioural events performed by dolphins. To date only one study has attempted to
      aggregate the behavioural events observed in a population in contextual groups
      using co-occurrence as the grouping factor. In the present study, I tried to
      characterise the behavioural repertoire of a bottlenose dolphin population
      (Tursiops sp.) present in Doubtful Sound, New Zealand. I first looked at the
      relationship between events performed by individuals depending on the behavioural
      state of their schools. I then assessed the likelihood for events to co-occur.
      Four main behavioural categories (orientation, travel, social displays and
      fights) emerged from this analysis. Aerial events (jumps) did not fall into one
      category, showing that different aerial behaviours play different roles.
      Moreover, it appears that dolphins used side-flopping and upside-down lobtailing
      to communicate motivation. Side-flops occurred when the focal schools finished a
      behavioural bout and started to travel, while upside-down lobtails occurred when
      the focal schools instigated a behavioural bout after travelling. This non-vocal
      communication can take place over a few meters to hundreds of meters. Having
      signals that are effective over very short ranges avoids unwanted signalling to
      prey, predators or conspecifics.

PMID- 16884865
TI  - Repeated weekly exposure to MDMA, methamphetamine or their combination: long-term
      behavioural and neurochemical effects in rats.
AB  - In recent work we have documented lasting adverse neurochemical and behavioural
      effects in rats given short-term 'binge' dosing with
      methylenedioxymethamphetamine (MDMA, Ecstasy), methamphetamine (METH) or their
      combination. Here we investigated whether similar effects persist in rats given
      16 weekly injections followed by a 10 week period of abstinence. Female rats
      received MDMA (8 mg/kg, i.p.), METH (8 mg/kg), or a MDMA/METH combination (4
      mg/kg MDMA + 4 mg/kg METH), once a week for 16 weeks, with locomotor activity and
      body temperature measured on weeks 1, 8 and 16. The MDMA and MDMA/METH groups
      showed acute drug-induced hyperthermia on week 1 only. MDMA-treated rats
      demonstrated an acute hyperactivity while METH and MDMA/METH treated rats showed
      pronounced stereotypy. Seven weeks after drug-treatment concluded, a decrease in
      social interaction was observed in all chronically drug-treated rats. No group
      differences were evident on the emergence, object recognition or forced swim
      tests. Neurochemical analysis revealed modest noradrenaline and serotonin
      depletion in chronically treated rats that was not evident following a single
      equivalent administration. These results indicate that although chronic,
      intermittent exposure to MDMA, METH or their combination, may not lead to
      significant long-term monoamine depletion, lasting adverse behavioural effects
      may persist, especially those related to social behaviour.

PMID- 16884866
TI  - Ovarian follicular superstimulation and oocyte maturation in the anoestrous
      southern hairy-nosed wombat, Lasiorhinus latifrons.
AB  - This study investigates the effect of three exogenous gonadotrophin regimens on
      ovarian follicular development in southern hairy-nosed wombats during the non
      breeding season. Females were given either porcine follicle stimulating hormone
      (pFSH; total of 200 mg at 12 h intervals over 7 (Group 1), or 4 days (Group 2)),
      or pregnant mares' serum gonadotrophin (PMSG; single dose of 150 I.U. (Group 3)).
      In all treatment groups 25 mg of porcine luteinising hormone (pLH) was used to
      trigger maturation; Groups 1 and 2 received pLH 12 h after the final pFSH
      injection and Group 3 received pLH 72 h after PMSG. The results showed Group 1
      produced significantly more follicles per ovary (5.91+/-1.28) than Group 2
      (1.67+/-0.62), or Group 3 (2.17+/-1.16) at p<0.05. Control females received
      saline injections concurrently with the three treatment groups (n=6; 2 control
      animals for each treatment group). No follicular development occurred in any
      control female. Analysis of oocyte nuclear status revealed that while oocytes
      from all three treatment groups had resumed meiosis, only those in Group 1 (7-day
      pFSH/pLH treatment) progressed to metaphase II. These results have implications
      for the development of assisted breeding strategies in this species.

PMID- 16884868
TI  - Development of 5-fluorouracil loaded poly(acrylamide-co-methylmethacrylate) novel
      core-shell microspheres: in vitro release studies.
AB  - Novel poly(acrylamide-methylmethacrylate) copolymeric core-shell microspheres
      crosslinked with N,N'-methylene bisacrylamide have been prepared by free radical
      emulsion polymerization using varying amounts of acrylamide (AAm),
      methylmethacrylate (MMA) and N,N'-methylene bisacrylamide (NNMBA). 5-Fluorouracil
      was loaded into these microspheres during in situ polymerization (method-I) as
      well as by the absorption and adsorption technique (method-II). The core-shell
      microspheres have been characterized by differential scanning calorimetry (DSC)
      and X-ray diffractometry (X-RD) to understand about the drug dispersion in
      microspheres. Scanning electron microscopy (SEM) was used to assess the surface
      morphology of particles prepared. In vitro release of 5-fluorouracil has been
      studied in terms of core-shell composition, amount of crosslinking agent and
      amount of 5-fluorouracil in the microspheres. Core-shell microspheres with
      different copolymer compositions have been prepared in yields ranging 80-85%. DSC
      and X-RD techniques indicated a uniform distribution of 5-fluorouracil particles
      in core-shell microspheres, whereas SEM suggested the formation of well-defined
      core-shell structures. The in vitro drug release indicated that particle size and
      release kinetics depend upon copolymer composition, amount of crosslinking agent
      used and amount of 5-fluorouracil present in the microspheres. Prolonged and
      controlled release of 5-fluorouracil was achieved when drug was loaded by method
      I instead of method-II.

PMID- 16884867
TI  - Contemporary alternatives to plant estrogens for menopause.
AB  - OBJECTIVES: Every year, millions of women begin the peri-menopause and may
      experience a number of symptoms related to this transition. Many women are
      reluctant to use exogenous hormone therapy for treatment of menopausal symptoms
      and are turning to botanical and dietary supplements (BDS) for relief. This paper
      reviews the literature on alternatives to plant estrogens for relief of
      menopausal symptoms. METHODS: The MEDLINE database was searched for clinical
      trials of non-estrogenic plant extracts for menopausal symptoms. To be included,
      studies had to include peri- or postmenopausal women as subjects. All clinical
      trials (randomized-controlled trials, open trials, and comparison group studies)
      were included for this review. RESULTS: Black cohosh appears to be one of the
      most effective botanicals for relief of vasomotor symptoms, while St. John's wort
      can improve mood disorders related to the menopausal transition. Many other
      botanicals have limited evidence to demonstrate safety and efficacy for relief of
      symptoms related to menopause. CONCLUSIONS: A growing body of evidence suggests
      that some botanicals and dietary supplements could result in improved clinical
      outcomes. Health care providers should discuss these issues with their patients
      so they can assist them in managing these alternative therapies through an
      evidence-based approach.

PMID- 16884869
TI  - Intravaginal ring delivery of the reverse transcriptase inhibitor TMC 120 as an
      HIV microbicide.
AB  - TMC 120 (Dapivirine) is a potent non-nucleoside reverse transcriptase inhibitor
      that is presently being developed as a vaginal HIV microbicide. To date, most
      vaginal microbicides under clinical investigation have been formulated as single
      dose semi-solid gels, designed for application to the vagina before each act of
      intercourse. However, a clear rationale exists for providing long-term,
      controlled release of vaginal microbicides in order to afford continuous
      protection against heterosexually transmitted HIV infection and to improve user
      compliance. In this study we report on the incorporation of various
      pharmaceutical excipients into TMC 120 silicone, reservoir-type intravaginal
      rings (IVRs) in order to modify the controlled release characteristics of the
      microbicide. The results demonstrate that TMC 120 is released in zero-order
      fashion from the rings over a 28-day period and that release parameters could be
      modified by the inclusion of release-modifying excipients in the IVR. The
      hydrophobic liquid excipient isopropyl myristate had little effect on steady
      state daily release rates, but did increase the magnitude and duration of burst
      release in proportion to excipient loading in the IVR. By comparison, the
      hydrophobic liquid poly(dimethylsiloxane) had little effect on TMC 120 release
      parameters. A hydrophilic excipient, lactose, had the surprising effect of
      decreasing TMC 120 burst release while increasing the apparent steady-state daily
      release in a concentration-dependent manner. Based on previous cell culture data
      and vaginal physiology, TMC120 is released from the various ring formulations in
      amounts potentially capable of maintaining a protective vaginal concentration. It
      is further predicted that the observed release rates may be maintained for at
      least a period of 1 year from a single ring device. TMC 120 release profiles and
      the mechanical properties of rings could be modified by the physicochemical
      nature of hydrophobic and hydrophilic excipients incorporated into the IVRs.

PMID- 16884871
TI  - Usefulness of traditionally defined herbal properties for distinguishing
      prescriptions of traditional Chinese medicine from non-prescription recipes.
AB  - Traditional Chinese medicine (TCM) has been widely practiced and is considered as
      an attractive to conventional medicine. Multi-herb recipes have been routinely
      used in TCM. These have been formulated by using TCM-defined herbal properties
      (TCM-HPs), the scientific basis of which is unclear. The usefulness of TCM-HPs
      was evaluated by analyzing the distribution pattern of TCM-HPs of the constituent
      herbs in 1161 classical TCM prescriptions, which shows patterns of multi-herb
      correlation. Two artificial intelligence (AI) methods were used to examine
      whether TCM-HPs are capable of distinguishing TCM prescriptions from non-TCM
      recipes. Two AI systems were trained and tested by using 1161 TCM prescriptions,
      11,202 non-TCM recipes, and two separate evaluation methods. These systems
      correctly classified 83.1-97.3% of the TCM prescriptions, 90.8-92.3% of the non
      TCM recipes. These results suggest that TCM-HPs are capable of separating TCM
      prescriptions from non-TCM recipes, which are useful for formulating TCM
      prescriptions and consistent with the expected correlation between TCM-HPs and
      the physicochemical properties of herbal ingredients responsible for producing
      the collective pharmacological and other effects of specific TCM prescriptions.

PMID- 16884870
TI  - Novel O-palmitoylscleroglucan-coated liposomes as drug carriers: development,
      characterization and interaction with leuprolide.
AB  - Polysaccharide-coated liposomes have been studied for their potential use for
      peptide drug delivery by the oral route because they are able to minimize the
      disruptive influences on peptide drugs of gastrointestinal fluids. The aim of
      this work was to synthesize and characterize a modified polysaccharide, O
      palmitoylscleroglucan (PSCG), and to coat unilamellar liposomes for oral delivery
      of peptide drugs. To better evaluate the coating efficiency of PSCG, also
      scleroglucan (SCG)-coated liposomes were prepared. We studied the surface
      modification of liposomes and the SCG- and PSCG-coated liposomes were
      characterized in terms of size, shape, zeta potential, influence of polymer
      coating on bilayer fluidity, stability in serum, in simulated gastric and
      intestinal fluids and against sodium cholate and pancreatin. Leuprolide, a
      synthetic superpotent agonist of luteinizing hormone releasing hormone (LHRH)
      receptor, was chosen as a model peptide drug. After polymer coating the vesicle
      dimensions increased and the zeta potential shifted to less negative values.
      These results indicate that both SCG- and PSCG-coated liposomes surface and DSC
      results showed that PSCG was anchored on the liposomal surface. The stability of
      coated-liposomes in SGF, sodium cholate solution and pancreatin solution was
      increased. From this preliminary in vitro studies, it seems that PSCG-coated
      liposomes could be considered as a potential carrier for oral administration.

PMID- 16884872
TI  - Applications of ENF criterion in forensic audio, video, computer and
      telecommunication analysis.
AB  - This article reports on the electric network frequency criterion as a means of
      assessing the integrity of digital audio/video evidence and forensic IT and
      telecommunication analysis. A brief description is given to different ENF types
      and phenomena that determine ENF variations. In most situations, to reach a non
      authenticity opinion, the visual inspection of spectrograms and comparison with
      an ENF database are enough. A more detailed investigation, in the time domain,
      requires short time windows measurements and analyses. The stability of the ENF
      over geographical distances has been established by comparison of synchronized
      recordings made at different locations on the same network. Real cases are
      presented, in which the ENF criterion was used to investigate audio and video
      files created with secret surveillance systems, a digitized audio/video recording
      and a TV broadcasted reportage. By applying the ENF Criterion in forensic
      audio/video analysis, one can determine whether and where a digital recording has
      been edited, establish whether it was made at the time claimed, and identify the
      time and date of the registering operation.

PMID- 16884873
TI  - STR data for the 15 loci from three minority populations in Guangxi municipality
      in South China.
AB  - In this study, allele frequencies for the 15 STRs (D8S1179, D21S11, D7S820,
      CSF1PO, D3S1358, TH01, D13S317, D16S539, D2S1338, D19S433, vWA, TPOX, D18S51,
      D5S818, FGA) included in the AmpFLSTR Identifiler kit were obtained from total of
      450 unrelated individuals belonging to three minority populations including Miao
      (n=141), Yi (n=165) and Hui (n=144) in Guangxi municipality, South China. GENEPOP
      v3.4 and PowerStats v1.2 was used to analyze the genotype data. This result
      indicates that the studied STR loci of these three minorities are useful in
      forensic testing and population genetics studies.

PMID- 16884874
TI  - Uncertainty of calculation results in vehicle collision analysis.
AB  - In the analysis of road accidents two types of calculation result uncertainty can
      be distinguished: modelling uncertainty and uncertainty in calculation results
      [R.M. Brach, M. Brach, Vehicle Accident Analysis & Reconstruction Methods, SAE
      International Publisher, Warrendale, 2005]. The problem becomes very important
      first of all when minor modifications of input parameters or application of
      different models of the phenomenon lead to a fundamentally different answer to
      the question posed by the court. The aim of the paper was to prove the necessity
      of including the problem of uncertainty in calculations related to vehicle
      collision mechanics and to justify the application of different error analysis
      methods recommendable in vehicle collision reconstruction. The data file from
      crash test No. 7 [H. Burg, M. Lindenmann, Unfallversuche, Verlag Information
      Ambs, Kippenheim, 1982] was used, the selection restricted to the range typical
      of average police records of collision place. Collision speeds were calculated
      using two methods: reconstruction and simulation. The analysis of uncertainty was
      carried out. Maximum and mean square uncertainty were calculated by means of
      total differential of relevant forms. Since the reconstruction resulted in very
      broad error intervals of uniform distribution, additional calculations were
      performed by the Monte Carlo method using algorithm described in [W. Wach, J.
      Unarski, Determination of vehicle velocities and collision location by means of
      Monte Carlo simulation method, Special Publication Accident Reconstruction SP
      1999, SAE Paper No. 2006-01-0907, 2006].

PMID- 16884875
TI  - SNP genotyping by multiplex amplification and microarrays assay for forensic
      application.
AB  - OBJECTIVE: Research on the application feasibility of SNP genotyping for forensic
      identification by microarrays. METHODS: Oligonucleotide microarrays which could
      detect 34 different SNPs were used. After hybridization and washing, the arrays
      were scanned and fluorescence intensities analyzed using Microarray software.
      Population studies on 34 SNP loci were carried out in a sample of 109 unrelated
      Chinese Han individuals using oligonucleotide microarrays for genotype detection.
      The method was also applied to cases. RESULTS: According to the results of
      population studies, no deviations from Hardy-Weinberg equilibrium could be found.
      Among the 34 loci, 3 SNPs were low informative, 4 were medium informative and 27
      were high informative. The combination discrimination power (CDP) of the 31
      optimal polymorphic SNPs was 0.9999999999979. The matching probability was 2.13 x
      10(-12). The average exclusion probability in paternity testing for duos was
      0.9609. The average exclusion probability in paternity testing for trios was
      0.9970. CONCLUSION: The data and case application demonstrated that SNP typing by
      oligonucleotide probe microarrays was a useful technique for paternity testing
      and individual identification. Combined with the 28 SNPs loci distributed on HLA
      DRB1 and ABO genes, the combination discrimination power (CDP) was
      0.9999999999999910. The matching probability was 9.02 x 10(-15). The average
      exclusion probabilities in duos and in trios were 0.9894 and 0.9992,
      respectively. It may be concluded that the 59 SNPs loci yield the same power in
      forensic identification as CODIS STRs currently used.

PMID- 16884876
TI  - Application of HLA-DRB1 genotyping by oligonucleotide micro-array technology in
      forensic medicine.
AB  - The human leukocyte antigen (HLA) system is known to be the most complex
      polymorphic system in the human genome. Among all of the HLA loci, HLA-DRB1 has
      the second largest number of alleles. The purpose of this study is to develop an
      oligonucleotide micro-array based HLA-DRB1 typing system for use in forensic
      identification, anthropology, tissue transplantation, and other genetic research
      fields. The system was developed by analyzing the HLA-DRB1 (DRB1) genotypes in
      1198 unrelated healthy Chinese Han individuals originating from various parts of
      China and residing in Shanghai, China. METHOD: Polymerase chain reaction (PCR)
      coupled with the oligonucleotide micro-array technology was used to detect and
      type HLA-DRB1 alleles of the sample individuals. The reliability, sensitivity,
      consistency and specificity were evaluated for use in forensic identification.
      Furthermore, a meta-analysis was carried out by comparing the allele frequencies
      of the HLA-DRB1 locus with those of other Chinese Han groups, Chinese minorities
      and other ethnic populations. RESULTS: All the DNA samples yielded a 273 bp
      amplification product, with no other amplification products in this length range.
      The minimum quantity of DNA detected by this method is 15 ng in a PCR reaction
      system of 25 microl. The population studied appeared to be not in Hardy-Weinberg
      equilibrium. Observed heterozygosity (Ho), expected heterozygosity (He), expected
      probability of exclusion (PE), polymorphic information content (PIC), and
      discrimination power (DP) of the HLA-DRB1 locus from the Shanghai Han ethnic
      group were evaluated to be 0.8022, 0.8870, 0.7741, 0.8771, 0.9750, respectively.
      A total of 25 HLA-DRB1 alleles were identified. HLA-DRB1*09XX, *04XX, *12XX and
      *15XX were the most frequent DRB1 alleles, which were observed in 58.76% of the
      sample. One hundred and sixteen genotypes were found. The five most frequent
      genotypes were: *04XX/*04XX (0.0626), *09XX/*09XX (0.0593), *04XX/*09XX (0.0551),
      *09XX/*15XX (0.0384) and *08XX/*12XX (0.0351). The meta-analysis showed that
      there were uniquely distributed features of DRB1 alleles among various ethnic
      populations and among the studied population groups from various regions with the
      same ethnic origin. CONCLUSIONS: An HLA-DRB1 genotyping system has been developed
      and established based on the oligonucleotide micro-array technology. The HLA-DRB1
      typing of the Han population in Shanghai has revealed a relatively high
      heterogeneity. Information obtained in this study will be useful for medical and
      forensic applications as well as in anthropology research. Large-scale micro
      array detection is highly accurate and reliable for DNA-based HLA-DRB1
      genotyping. These results suggest that HLA-DRB1 DNA polymorphisms and the
      database of the Shanghai Han group have useful applications in processing
      forensic casework (as personal identification, paternity test), tracing
      population migration and genetic diagnosis.

PMID- 16884877
TI  - How do forensic scientists learn to become competent in casework reporting in
      practice: a theoretical and empirical approach.
AB  - In their day-to-day work, carrying out complex tasks, forensic scientists use a
      combination of explicit, codified standard operating procedures and tacit
      knowledge developed through their ongoing practice. We show that tacit knowledge
      is an integral part of the activities of expert forensic science practitioners
      who continually add to their knowledge repertoire by engaging other scientists
      through communities of practice. We wish to shed fresh light on the gaining of
      tacit knowledge by forensic scientists during their apprentice formative years,
      termed as legitimate peripheral participation. In quantifying tacit knowledge
      exchanges, we use social network analysis, a methodology for the analysis of
      social structures, to map relational knowledge flows between forensic scientists
      within communities of practice at the Forensic Science Laboratory, Ireland. This
      paper sheds light on the importance of tacit knowledge within the training regime
      of forensic scientists and its recognition as equal to the part played by
      explicit knowledge.

PMID- 16884878
TI  - Pattern detection in forensic case data using graph theory: application to heroin
      cutting agents.
AB  - Pattern recognition techniques can be very useful in forensic sciences to point
      out to relevant sets of events and potentially encourage an intelligence-led
      style of policing. In this study, these techniques have been applied to
      categorical data corresponding to cutting agents found in heroin seizures. An
      application of graph theoretic methods has been performed, in order to highlight
      the possible relationships between the location of seizures and co-occurrences of
      particular heroin cutting agents. An analysis of the co-occurrences to establish
      several main combinations has been done. Results illustrate the practical
      potential of mathematical models in forensic data analysis.

PMID- 16884879
TI  - Population data from sub-populations of the Northern Territory of Australia for
      15 autosomal short tandem repeat (STR) loci.
AB  - It is a requirement that forensic DNA profiling evidence be accompanied by an
      estimation of its weight, in order that the court can assign an appropriate
      probative value to the evidence during legal proceedings. There are various
      models by which this estimation can be made, but each relies on approximations of
      the allele frequencies in the relevant population. It is also important to assess
      relevant population genetic features of the available data. This report provides
      allele frequencies and estimates of common population genetic parameters for the
      major sub-populations of the Northern Territory of Australia genotyped at 15
      autosomal short tandem repeat (STR) loci.

PMID- 16884880
TI  - Superimposition and projective transformation of 3D object.
AB  - Superimposition is an efficient method for evaluation of coincidence between a
      skull and a photo portrait. The principle of superimposition method lies in the
      projection of the skull into the face image. During the projection of an object
      with a perspective camera, the mapping of a three-dimensional object into a two
      dimensional image takes place. The acquired images of the same object are more or
      less distorted due to various photographic conditions, due to extrinsic and
      intrinsic parameters of the camera. The distortions have important influence onto
      reliability of human identification by the superimposition method. Mathematically
      we can describe most of the distortions. On the basis of the description the
      divergences could be simulated and in some cases eliminated by geometric
      transformation of the compared images. We are presenting a mathematical model of
      the standard projective camera and the mathematical description of distortions
      which are important for the superimposition process. The results show the
      distortions and the elimination of the distortions by means of the projection
      model.

PMID- 16884881
TI  - Y chromosome haplotypes in Central-South Italy: implication for reference
      database.
AB  - One hundred and fifty individuals have been sampled across Central-South Italy
      and genotyped for Y chromosome STRs by PowerPlex Y system. Comparison with
      previous Italian databases revealed that majority of Y chromosome variation still
      need to be sampled. Identification of locus duplications, distribution of genetic
      variation and firstly identified alleles point to the necessity of more focused
      sampling strategies for reference databases.

PMID- 16884882
TI  - Determination of arbidol in human plasma by LC-ESI-MS.
AB  - A sensitive, specific and accurate method for determination of arbidol in human
      plasma was developed. Arbidol and internal standard were extracted from plasma
      samples by liquid-liquid extraction with diethyl ether. The chromatographic
      separation was accomplished on a Shiseido C18 3 microm analytical column (100 mm
      x 2.0 mm i.d.) at a flow rate of 0.3 mL/min isocratically. Detection was
      performed on a single quadrupole mass spectrometer by selected ion monitoring
      (SIM) mode via electrospray ionization (ESI) source. The method had a
      chromatographic run time of 6 min and a good linear relationship over the range 1
      1000 ng/mL. The limit of quantitation for arbidol in plasma was 1 ng/mL. The
      intra-day and inter-day precision (R.S.D.%) was lower than 7% and accuracy ranged
      from 95 to 105%. The proposed method enables unambiguous identification and
      quantification of arbidol in vivo and has been successfully applied to study the
      pharmacokinetics of arbidol in healthy male Chinese volunteers.

PMID- 16884883
TI  - Performance characteristics of two immunoassays for the measurement of urinary
      luteinizing hormone.
AB  - Urine luteinizing hormone (LH) concentration is routinely measured in all anti
      doping laboratories to exclude recombinant LH abuse and to test any potential
      alteration of the hypophyseal-gonadal axis. Before establishing proper reference
      values among professional top level athletes, an extended validation of two
      commercial immunoassays for LH measurements was performed. Elecsys 1010 and
      Access are two automated immunoanalyzers for central laboratories. The limit of
      detection, the limit of quantification, intra-laboratory, inter-technique
      correlation, precision, accuracy were determined. Furthermore, reference urinary
      LH distribution values for male and female top level athletes were determined.
      Stability studies of LH in urine following freezing and thawing cycles (n=3) as
      well as storage conditions at room temperature, 4 degrees C and -20 degrees C
      were performed. Male and female subjects showed important urinary corrected
      (specific gravity correction) LH distribution differences. Intra-assay precision
      for the Access analyzer was less than 8.0% whereas inter-assay was close to 11%.
      Intra and inter-assay precision for the Elecsys 1010 analyzer was slightly
      better. A good inter-technique correlation was obtained ([Elecsys
      1010]=1.0434[Access]+1.146, R=0.953). No urinary LH loss was observed after two
      freezing and thawing cycles. On the other hand, time and bad storage conditions
      such as elevated temperature can deteriorate rapidly urinary LH. In conclusion,
      both analyzers showed acceptable performances and are suitable for screening anti
      doping analyses. Each anti-doping laboratory has to settle its own reference
      distribution values and then determine when to launch a confirmation procedure.
      This takes place then depending on the positivity criteria the anti-doping
      laboratory has established and validated. This study also clearly showed that the
      time delay between the urine collection and the analysis should be reduced as
      much as possible and urine samples should be transported in optimal conditions
      (low temperature and quickly) to decrease urinary LH deterioration.

PMID- 16884884
TI  - Determination of doxorubicin in rabbit ocular tissues and pharmacokinetics after
      intravitreal injection of a single dose of doxorubicin-loaded poly-beta
      hydroxybutyrate microspheres.
AB  - A validated HPLC method was developed for the quantification of doxorubicin in
      rabbit ocular tissues using solid phase extraction and ultraviolet detection.
      Chromatographic separation of doxorubicin in various ocular tissues was performed
      on a C18 column. The mobile phase was composed of 0.2 M KH2PO4 buffer solution,
      acetonitrile and triethylamine in volumetric ratio of 70/30/0.2, adjusted to pH
      4.0 with orthophosphoric acid. The calibration curve was linear over the range of
      0.03-10, 0.03-10, 0.05-10 and 0.05-10 microg/ml in vitreous body, iris,
      retina/choroids and sclera, respectively. The intra-day and inter-day precisions
      in all ocular tissues were smaller than 4.95% and 5.73%, and the accuracies were
      about 100%. The extraction recoveries of doxorubicin in all of the ocular tissues
      were between 83.47% and 96.33%. After intravitreal administration of doxorubicin
      loaded poly-beta-hydroxybutyrate microspheres, doxorubicin level in ocular
      tissues was much lower than that for administration of free doxorubicin, which
      was helpful to reduce the associated toxicity to surrounding tissues. Doxorubicin
      was detectable even after tens of days in the studied ocular tissues.

PMID- 16884886
TI  - High-performance liquid chromatographic analysis of pterostilbene in biological
      fluids using fluorescence detection.
AB  - A method of analysis of pterostilbene [trans-3,5-dimethoxy-4'-hydroxystilbene] is
      necessary to study the kinetics of in vitro and in vivo metabolism and determine
      its concentration in foodstuffs. A novel and simple high-performance liquid
      chromatographic method was developed for determination of pterostilbene in rat
      serum. Serum proteins (0.1 mL) are precipitated with cold acetonitrile after
      addition of the internal standard, pinosylvin. Separation was achieved on a
      Phenomenex C18 column (250 mm x 4.60 mm) with fluorescence excitation at 330 nm
      and emission at 374 nm. The calibration curves were linear ranging from 0.5 to
      100 microg/mL. The mean extraction efficiency was >99%. Precision of the assay
      was <15% (CV), and was within 14% at the limit of quantitation (0.5 microg/mL).
      Bias of the assay was lower than 14%, and was within 9% at the limit of
      quantitation. The assay was applied successfully to the study of pterostilbene
      pharmacokinetics in rats.

PMID- 16884885
TI  - LC-APCI-MS method for detection and analysis of tryptanthrin, indigo, and
      indirubin in daqingye and banlangen.
AB  - A rapid, selective, and sensitive LC-APCI-MS method is developed in this study
      for detecting and analyzing tryptanthrin, indigo, and indirubin in daqingye and
      banlangen, which are, respectively, the leaves and roots of Isatis indigotica and
      Strobilanthes cusia in traditional Chinese medicine. The detection of the three
      active components is linear in concentrations ranging from 100 to 1500 ng/mL, the
      squared correlation coefficient is higher than 0.996, the precision as measured
      by the relative standard deviation is no larger than 9.5%, and the recovery is
      greater than 86.6%. The analysis of the 21 banlangen samples led to considerably
      different conclusions on the contents of tryptanthrin, indigo, and indirubin in
      fresh leaves versus those in dried leaves. These results should shed some light
      on future plant selection and breeding. Compared with the traditional TLC and
      HPLC-UV methods, the new LC-APCI-MS approach has proven to be an optimal tool for
      detecting and analyzing the three marker compounds in the Chinese herbal
      medicines of daqingye and banlangen.

PMID- 16884887
TI  - An evaluation of four commercial HPLC chiral detectors: a comparison of three
      polarimeters and a circular dichroism detector.
AB  - With increasing frequency, new drug candidates being introduced into
      pharmaceutical drug pipelines are chiral. Often only one enantiomer exhibits the
      desired biological activity and the other enantiomer may exhibit undesired side
      effects, thereby making chiral purity an important parameter. The introduction of
      chiral analysis adds additional complications in drug development. The
      pharmaceutical industry is constantly striving to streamline processes and
      improve efficiencies in an effort to move molecules to market quickly. In order
      to simplify the process of chiral method development, chiral screening can be set
      up, however a successful chiral screen depends on optimizing two factors: the
      column and the detector. The following work investigated the second factor and
      evaluated two types of commercially available chiral detectors for their possible
      use in chiral method development and screening: polarimeters and circular
      dichroism (CD) detectors. Linearity, precision, and the limit of detection (LD)
      of six compounds (trans-stilbene oxide, ethyl chrysanthemate, propranolol, 1
      methyl-2-tetralone, naproxen, methyl methionine) on four commercial detectors
      (three polarimeters and one CD detector) were determined experimentally and the
      limit of quantitation (LQ) calculated from the experimental LD. Trans-stilbene
      oxide worked well across all the detectors, showing good linearity, precision and
      low detection limits. However, the other five compounds proved to be more
      discriminating and showed that the circular dichroism detector performed better
      as a detector for chiral screens, over the polarimeters.

PMID- 16884888
TI  - A critical review of FDA-approved Medication Guides.
AB  - OBJECTIVE: To investigate whether consumer-directed, FDA-approved Medication
      Guides issued for potentially harmful medications are likely to be useful to
      patients with limited literacy. METHODS: Lexile analysis and the suitability
      assessment of materials (SAM) were conducted on the 40 currently issued
      Medication Guides to evaluate reading difficulty, content, and format. Structured
      interviews with a literacy assessment were also conducted among 251 primary care
      patients at a public hospital clinic in Louisiana to determine if patients
      directed attention to Medication Guides and other accompanying patient
      information materials. RESULTS: The average Lexile score estimated an 11th-12th
      grade reading level for the guides (M=1223, S.D.=200). None of the 40 Medication
      Guides met federal recommendations (6th-8th grade level). Most Medication Guides
      were deemed unsuitable because they did not provide a summary of content (90.0%)
      or limit the scope of information (77.5%). Only 23.0% of patients reported having
      looked at Medication Guides or accompanying patient information materials;
      patients with low literacy were less likely to have looked at them (16.7% versus
      32.9%, p=0.03). CONCLUSION: Medication Guides in their current form are not
      likely to be useful to patients with limited literacy skills. PRACTICE
      IMPLICATIONS: Reading level of text in Medication Guides should be reduced,
      summaries or "highlights" provided, and the scope of information limited to
      increase the likelihood of use among individuals with limited literacy. Consumers
      should be involved in their development.

PMID- 16884889
TI  - Effect of selected insecticides on growth rate and stress protein expression in
      cultured human A549 and SH-SY5Y cells.
AB  - Two organochlorines (dienochlor, endosulfan) and one neonicotinoid (imidacloprid)
      insecticides were investigated as putative cellular aggressors, both as pure
      chemicals and as commercial formulations, in order to evaluate the additional
      toxicity due to additives present in the commercial formulations. Toxicity was
      evaluated on human cells in vitro, by culturing neuronal SH-SY5Y and pulmonary
      A549 cell lines for 3 days in the presence of increasing concentrations of the
      selected pesticides. LOEC (lowest observed effect concentration), IC50
      (concentration leading to a 50% decrease of cell growth) and expression changes
      of molecular chaperones involved in cellular protein quality control were
      determined. The investigated molecular chaperones were the cytosolic resident
      heat shock proteins (HSP27, HSP72/73, and HSP90) and the glucose regulated
      proteins (GRP78, GRP94) located in the endoplasmic reticulum (ER).
      Organochlorines were found to be the most toxic in both A549 and SH-SY5Y cells,
      IC50 being respectively 0.95 and 0.36 microM for dienochlor, 34 and 20 microM for
      endosulfan, 1.8 and 1.5 mM for imidacloprid. This shows that neuronal cells were
      more sensitive than pulmonary cells. LOEC and IC50 appeared at lower
      concentrations of active molecule when using the commercial formulations
      Techn'ufan (endosulfan) and Confidor (imidacloprid), indicating an additional
      adverse effect of additives. Insecticide concentrations higher than IC50 were
      found to induce an underexpression of all cytosolic HSPs, probably resulting from
      a general inhibition of protein synthesis. HSP27 was found to be underexpressed
      at concentrations of imidacloprid or endosulfan (as Techn'ufan) lower than IC50.
      This underexpression of the anti-apoptotic HSP27 could contribute to the increase
      of cell mortality. GRP78 was up-regulated by endosulfan in A549, but not in SH
      SY5Y cells, suggesting a damaging effect on proteins specific to pulmonary cells.
      Conversely, HSP72/73 was found to be down-regulated, resulting probably from the
      ER unfolded protein response (UPR) as previously reported [Skandrani, D., Gaubin,
      Y., Vincent, C., Beau, B., Murat, J.C., Soleilhavoup, J.P., Croute, F., 2006.
      Relationship between toxicity of selected insecticides and expression of stress
      protein (HSP, GRP) in cultured human cells: effects of commercial formulations
      versus pure active molecules. Biochim. Biophys. Acta 1760 (1), 95-103].

PMID- 16884890
TI  - An empirical analysis of the BASC Frontal Lobe/Executive Control scale with a
      clinical sample.
AB  - Data from a clinical sample of children and adolescents were used to examine the
      characteristics of the Frontal Lobe/Executive Control (FLEC) scale of the
      Behavior Assessment System for Children Parent Rating Scales, including
      preliminary evidence of the scale's clinical utility and relationship to other
      behavioral measures of executive function and characteristics of Attention
      Deficit Hyperactivity Disorder (ADHD). Results indicate that participants in the
      ADHD and other clinical groups received very similar scores on the FLEC scale,
      and both groups were rated significantly higher in behaviors associated with
      executive dysfunction than were participants in the no diagnosis group.
      Correlational results indicate that scores on the FLEC scale were significantly
      correlated with scores on the Behavior Rating Inventory of Executive Function
      Parent Form and Conners' Parent Rating Scales Revised-Short Form. Based on our
      results, the FLEC scale appears to be a useful behavioral rating tool in the
      assessment of executive function that may serve as a supplement to more
      traditional measures.

PMID- 16884891
TI  - Construction of a California condor BAC library and first-generation chicken
      condor comparative physical map as an endangered species conservation genomics
      resource.
AB  - To support genomic analysis of the endangered California condor (Gymnogyps
      californianus), a BAC library (CHORI-262) was generated using DNA from the blood
      of a female. The library consists of 89,665 recombinant BAC clones providing
      approximately 14-fold coverage of the presumed approximately 1.48-Gb genome.
      Taking advantage of recent progress in chicken genomics, we developed a first
      generation comparative chicken-condor physical map using an overgo hybridization
      approach. The overgos were derived from chicken (164 probes) and New World
      vulture (8 probes) sequences. Screening a 2.8x subset of the total library
      resulted in 236 BAC-gene assignments with 2.5 positive BAC clones per successful
      probe. A preliminary comparative chicken-condor BAC-based map included 93 genes.
      Comparison of selected condor BAC sequences with orthologous chicken sequences
      suggested a high degree of conserved synteny between the two avian genomes. This
      work will aid in identification and characterization of candidate loci for the
      chondrodystrophy mutation to advance genetic management of this disease.

PMID- 16884892
TI  - Performance of a seizure warning algorithm based on the dynamics of intracranial
      EEG.

PMID- 16884893
TI  - Phenotypes and genotypes in epilepsy with febrile seizures plus.
AB  - In the last several years, mutations of sodium channel genes, SCN1A, SCN2A, and
      SCN1B, and GABA(A) receptor gene, GABRG2 were identified as causes of some
      febrile seizures related epilepsies. In 19 unrelated Japanese families whose
      probands had febrile seizures plus or epilepsy following febrile seizures plus,
      we identified 2 missense mutations of SCN1A to be responsible for the seizure
      phenotypes in two FS+ families and another mutation of SCN2A in one family. The
      combined frequency of SCN1A, SCN2A, SCN1B, SCN2B, and GABRG2 mutations in
      Japanese patients with FS+ was 15.8%. One family, which had R188W mutation in
      SCN2A, showed digenic inheritance, and another modifier gene was thought to take
      part in the seizure phenotype. The phenotypes of probands were FS+ in 5, FS+ and
      partial epilepsy in 10, FS+ and generalized epilepsy in 3, and FS+ and
      unclassified epilepsy in 1. We proposed the term epilepsy with febrile seizures
      plus (EFS+), because autosomal-dominant inheritance in EFS+ might be rare, and
      most of EFS+ display a complex pattern of inheritance, even when it appears to be
      an autosomal-dominant inheritance. There is a possibility of simultaneous
      involvement of multiple genes for seizure phenotypes.

PMID- 16884894
TI  - The conviction of delusional beliefs scale: reliability and validity.
AB  - This study reports on the development of a new measure of delusional belief
      conviction, the Conviction of Delusional Beliefs Scale (CDBS). Most of the
      current scales in use assess belief conviction with a single item and primarily
      reflect the cognitive aspects of conviction. The CDBS represents an improvement
      over existing scales in that it contains a larger number of test items that can
      be subjected to psychometric examination. In addition, the CDBS also broadens the
      concept of belief conviction by incorporating cognitive, emotional, and
      behavioral items. In the present study, fifty participants with delusions
      completed the CDBS along with measures of delusional ideation, psychiatric
      symptomatology, insight, and reading ability. The CDBS showed very good levels of
      internal consistency and test-retest stability over a six-week period. All of the
      CDBS items loaded highly on a unitary factor of belief conviction. The CDBS
      positively correlated with four measures of belief conviction thereby reflecting
      the convergent validity of the scale. The CDBS was unrelated to other dimensions
      of delusional ideation, psychiatric symptomatology, insight, and reading ability,
      which supported the discriminant validity of the scale. The CDBS appears to be a
      reliable and valid measure of delusional belief conviction that could be used in
      clinical and research settings.

PMID- 16884895
TI  - Low rates of treatment for hypertension, dyslipidemia and diabetes in
      schizophrenia: data from the CATIE schizophrenia trial sample at baseline.
AB  - Persons diagnosed with schizophrenia have higher morbidity and mortality rates
      from cardiovascular disease, yet often have limited access to appropriate primary
      care screening or treatment. Metabolic disorders such as diabetes, hyperlipidemia
      and hypertension are highly prevalent in populations with schizophrenia,
      exceeding 50% in some studies; however, there have been few published studies on
      treatment rates among schizophrenia patients screened for these disorders.
      METHODS: Using the baseline data from subjects (N=1460) recruited into the
      Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia
      study, we examined the point prevalence of diabetes, hyperlipidemia and
      hypertension treatment at the time of enrollment for the entire cohort and those
      with fasting laboratory values obtained 8 or more hours since last meal. RESULTS:
      Rates of non-treatment ranged from 30.2% for diabetes, to 62.4% for hypertension,
      and 88.0% for dyslipidemia. Nonwhite men were more likely to be treated for DM
      and dyslipidemia than nonwhite women. CONCLUSIONS: These data indicate the high
      likelihood that metabolic disorders are untreated in patients with schizophrenia,
      with particularly high rates of non-treatment for hypertension and dyslipidemia.
      Nonwhite women may be especially vulnerable to undertreatment of dyslipidemia and
      diabetes compared to nonwhite men. The findings here support the need for
      increased attention to basic monitoring and treatment of cardiovascular risk
      factors in this vulnerable and often underserved psychiatric population.

PMID- 16884896
TI  - Preparation and characterization of polymeric micelles for solubilization of
      poorly soluble anticancer drugs.
AB  - The objective of this study is to investigate the solubilization of poorly water
      soluble anticancer drugs, octaethylporphine (OEP), meso-tetraphenyl porphine
      (mTPP) and camptothecin (CPT), in Pluronic and polyethylene glycol
      distearoylphosphatidylethanolamine (PEG-DSPE) polymeric micelles. Three different
      Pluronic and PEG-DSPE polymers with various chain lengths were chosen and micelle
      formulations were prepared by using various drug:polymer ratios. Formulations
      were characterized by critical micellization concentration (CMC) values of
      copolymers, micelle particle size and distribution, zeta potential, loading
      efficiency and stability. Polymers formed very stable, low CMC micelles with
      smaller sizes than 100 nm. It was shown that drug loading efficiency highly
      depends on the polymer type, drug type and their ratios. The most efficient drug
      loading was obtained by loading mTPP in PEG2000-DSPE and Pluronic F127 micelles.
      This result is attributed to phenyl groups in mTPP might lead to attraction
      between alkyl groups in the polymer and increase drug incorporation. PEG-DSPE
      formulations had higher zeta potential values indicating that they would be more
      stable against aggregation than Pluronic micelles. From the drug assay aspect
      Pluronic micelles remained more stable in 3-month long stability test. These
      results showed that besides their solubilizing effects, polymeric micelles could
      be useful as novel drug carriers for hydrophobic drugs.

PMID- 16884897
TI  - Feasibility of simple chitosan sheet as drug delivery carrier.
AB  - Chitosan, a biodegradable and biocompatible polysaccharide, is a potentially
      useful material in various fields. We developed a simple chitosan sheet and
      examined the possibility of using an adriamycin-containing chitosan sheet as a
      drug carrier for controlled release. To prepare a carrier consisting only of
      chitosan, a chitosan suspension was subjected to acid-alkaline treatment, mixed
      with adriamycin, frozen and freeze-dried. The adriamycin-containing chitosan
      sheet was inserted into the peritoneal cavity of mice in order to investigate its
      biodegradation. The appearance of decomposition of chitosan was observed using
      scanning electron microscopy, and adriamycin in urine and liver was detected for
      1 and 2 weeks, respectively. Adriamycin metabolites were detected in plasma for 2
      weeks. Furthermore, adriamycin remained in the chitosan sheet without being
      metabolized after 2 months. These results suggested that the chitosan sheet
      prepared in this study might improve therapeutic efficacy in topical lesions as a
      carrier of sustained-release drugs.

PMID- 16884899
TI  - A gender perspective on parents' answers to a questionnaire on children's asthma.
AB  - BACKGROUND: Is there a difference in the answers of mothers and fathers to the
      Paediatric Caregiver's Quality of Life Questionnaire (PACQLQ)? If so, does this
      reflect a perception that has any consequence for the medication and health of
      the child? METHODS: We performed a randomised prospective intervention study with
      extra support and education in the form of group discussions with half of the
      parents of 60 pre-school children with newly diagnosed asthma. Parents answered
      separately the PACQLQ at inclusion, and after 6 and 18 months. RESULTS: There
      were no major gender differences in indices at any occasion, but mothers were
      more disturbed at night, felt more helpless and frightened and the child's asthma
      interfered more with their work at inclusion. After 6 months the mothers in the
      intervention group showed improvements in all indices. After 18 months the
      children in the intervention group had better adherence and their exacerbation
      rate was half that of the control group. In the region where this method now is
      standard the in-hospital days with asthma are the lowest in the country.
      CONCLUSION: There are differences in the answers of fathers and mothers to the
      PACQLQ. In the intervention group the mothers reported that they were less
      worried and less restricted in their activities. This equalisation of the
      parent's roles in handling their child's asthma might be part of the explanation
      as to why the children in the intervention group had better adherence and were
      healthier.

PMID- 16884898
TI  - Recent advances in the immunogenetics of human type 1 diabetes.
AB  - Type 1 diabetes (T1D), a disorder of glucose homeostasis, is caused by autoimmune
      destruction of the essential insulin-secreting beta cells in the pancreas. Both
      genetic and environmental factors contribute to the risk of T1D and, for decades,
      this complexity has challenged investigators interested in identifying the genes
      that contribute to this risk. Nevertheless, in recent years, a number of well
      supported T1D risk loci have been identified and replicated. Owing to development
      of more powerful study designs, the availability of dense marker maps, progress
      in high-throughput genotyping and a better basic understanding of the roles of
      genes in the immune system, this trend is likely to continue.

PMID- 16884901
TI  - Detection of DNA using cationic polyhedral oligomeric silsesquioxane
      nanoparticles as the probe by resonance light scattering technique.
AB  - A novel cationic polyhedral oligomeric silsesquioxane nanoparticle (cationic
      POSS) was synthesized and successfully used as a new probe for the detection of
      DNA by resonance light scattering technique (RLS). It was found that the
      electrostatic interaction of cationic POSS and DNA could obviously enhance the
      RLS signal, the enhanced RLS intensity at 360 nm was proportional to the
      concentration of nucleic acids within the range of 0.35-42.82 microg ml-1 for
      calf thymus DNA, the determination limit (3sigma) was 0.32 ng ml-1. The results
      showed this method was very sensitive, convenient, rapid and reproducible.

PMID- 16884900
TI  - Quartz crystal microbalance immunosensors for environmental monitoring.
AB  - This paper presents discussion of quartz crystal microbalance (QCM) immunosensors
      for environmental monitoring. Factors limiting the practical application of
      antibodies to analytical problems are also presented. Among several candidates
      for the QCM immunosensor device, selected QCM devices and oscillating circuits
      were tested thoroughly and developed to obtain highly stable and sensitive
      frequency signals. The biointerface of QCM immunosensor was designed and
      controlled to immobilize antibody on the QCM surface, to reduce non-specific
      binding and to suppress denaturation of immobilizing antibody by self-assembled
      monolayer technique and artificial phospholipid (2-methacryloyloxyethyl
      phosphorylcholine (MPC)) polymer. MPC polymer as a antibody-stabilizing reagent
      was added to reduce non-specific binding of the antigen solution and stabilize
      the immunologic activity of the antibody-immobilized QCM. In addition, it
      provides examples for detection and quantitation of environmental samples using
      QCM immunosensors. The analytical results for fly ash extracted samples of
      dioxins using the QCM immunosensor indicated a good relationship with GC/MS
      methods. The integrating protocols of the competitive immunoassay and signal
      enhancing step are for detecting low molecular analytes with extremely low
      detection limits using an QCM immunosensor. Furthermore, its detect limitation
      was extended from 0.1 to 0.01 ng/ml by the signal-enhancing step when the anti
      bisphenol-A antibody conjugated MPC polymeric nanoparticles was used. The QCM
      immunosensor method has demonstrated its effectiveness as an alternative
      screening method for environmental monitoring because these results were compared
      with results obtained through environmental monitoring methods such as ELISA and
      GC/MS.

PMID- 16884902
TI  - A novel detection strategy for odorant molecules based on controlled
      bioengineering of rat olfactory receptor I7.
AB  - In this study, we report a dose-dependent detection of odorant molecules in
      solution by rat olfactory receptor I7 (OR I7) in its membrane fraction. The OR I7
      is immobilized on a gold electrode by multilayer bioengineering based on a mixed
      self-assembled monolayer and biotin/avidin system, which allows for a well
      controlled immobilization of the bioreceptor within its lipid environment. The
      odorant detection is electronically performed in a quantitative manner by
      electrochemical impedance spectroscopy (EIS) measurements on samples and
      controls.

PMID- 16884903
TI  - Influence of electrolytes in the QCM response: discrimination and quantification
      of the interference to correct microgravimetric data.
AB  - In this work we demonstrate that the presence of electrolytes in solution
      generates desorption-like transients when the resonance frequency is measured.
      Using impedance spectroscopy analysis and Butterworth-Van Dyke (BVD) equivalent
      electrical circuit modeling we demonstrate that non-Kanazawa responses are
      obtained in the presence of electrolytes mainly due to the formation of a diffuse
      electric double layer (DDL) at the sensor surface, which also causes a capacitor
      like signal. We extend the BVD equivalent circuit by including additional
      parallel capacitances in order to account for such capacitor like signal.
      Interfering signals from electrolytes and DDL perturbations were this way
      discriminated. We further quantified as 8.0+/-0.5 Hz pF-1 the influence of
      electrolytes to the sensor resonance frequency and we used this factor to correct
      the data obtained by frequency counting measurements. The applicability of this
      approach is demonstrated by the detection of oligonucleotide sequences. After
      applying the corrective factor to the frequency counting data, the mass
      contribution to the sensor signal yields identical values when estimated by
      impedance analysis and frequency counting.

PMID- 16884904
TI  - The clinical trail of TRAIL.
AB  - The naturally occurring tumour necrosis factor related apoptosis-inducing ligand
      (TRAIL) induces apoptosis through two death receptors, death receptor 4 (DR4) and
      death receptor 5 (DR5), that are expressed on the cell membrane. Binding of the
      ligand to the death receptors leads to activation of the extrinsic apoptosis
      pathway. Chemotherapy on the other hand stimulates the intrinsic apoptosis
      pathway via activation of p53 in response to cellular damage. Many cancer cells
      have mutations in p53 causing resistance to chemotherapy-induced apoptosis.
      Concomitant signalling through the extrinsic pathway may overcome this
      resistance. Moreover, enthusiasm for TRAIL as an anticancer agent is based on the
      demonstration of rhTRAIL-induced selective cell death in tumour cells and not in
      normal cells. In this review, we provide an overview of the TRAIL pathway, the
      physiological role of TRAIL and the factors regulating TRAIL sensitivity. We also
      discuss the clinical development of novel agents, i.e. rhTRAIL and agonistic
      antibodies, that activate the death receptors.

PMID- 16884905
TI  - Optimization of extracellular keratinase production by poultry farm isolate
      Scopulariopsis brevicaulis.
AB  - A Scopulariopsis brevicaulis poultry farm isolate was chosen to study factors
      influencing keratinase production. The parameters were optimized by factorial
      design. The highest enzyme production by this fungus was obtained at pH 7.5, a
      temperature of 30 degrees C and a growth period of 5 weeks. The production of the
      enzyme was enhanced when the culture medium was supplemented with glucose (1%),
      sodium nitrate (2%), feather (1.5%) and CaCl(2) (1 mM). According to the
      responses from the experimental design, the effects of each variable were
      calculated, and the interactions between them were determined. The experimental
      values were found to be in accordance with the predicted values, the correlation
      coefficient is 0.9978.

PMID- 16884906
TI  - Effect of tetrahydrobiopterin on selective endothelial dysfunction of epicardial
      porcine coronary arteries induced by cardiopulmonary bypass.
AB  - BACKGROUND: We hypothesized that cardiopulmonary bypass induces a selective
      alteration of the coronary arterial endothelial cell signal transduction which
      could be explained by a state of depletion and/or decreased activity of
      endogenous tetrahydrobiopterin (BH(4)). The aim of this study was to assess the
      effects of cardiopulmonary bypass and BH(4) on the endothelial function of
      epicardial coronary arteries in a swine model of cardiopulmonary bypass. METHODS:
      Swine underwent 90 min of cardiopulmonary bypass alone (N=19) or in association
      with a brief cardioplegic arrest with (N = 6) or without (N = 5) in vivo BH(4)
      administration, followed by a 60-min period following weaning from
      cardiopulmonary bypass and were compared to a control group (N = 7). Endothelium
      dependent relaxations of epicardial coronary artery rings were studied using
      standard organ chamber experiments in the presence or absence of in vitro BH(4)
      or superoxide dismutase (SOD) and catalase. RESULTS: Cardiopulmonary bypass
      caused a statistically significant reduction of endothelium-dependent relaxations
      to serotonin (p < 0.0001), bradykinin (p < 0.001), UK14304 (p < 0.0001) and
      calcium ionophore (p < 0.01) in epicardial porcine coronary arteries. In vitro
      and in vivo BH(4) supplementation improved endothelium-dependent relaxations to
      serotonin and bradykinin, which were left unchanged by SOD-catalase
      administration. Cardiopulmonary bypass was associated with a decrease in nitric
      oxide availability (p = 0.002) and increased oxidative stress (p < 0.001), which
      were both restored by in vivo BH(4) administration (p < 0.001). CONCLUSION:
      Treatment with BH(4) improves the endothelial dysfunction of porcine epicardial
      coronary arteries, restores nitric oxide availability and reduces the oxidative
      stress associated with cardiopulmonary bypass.

PMID- 16884907
TI  - Pulmonary endarterectomy: is there an alternative to profound hypothermia with
      cardiocirculatory arrest?
AB  - The current surgical strategy for pulmonary endarterectomy (PEA) involves the use
      of extracorporeal circulation and hypothermic circulatory arrest (HCA). The aim
      of the present study was to test the feasibility of a different strategy of
      extracorporeal circulation, which could prevent bronchial back bleeding and allow
      a bloodless operating field, avoiding the risks associated with HCA in patients
      undergoing pulmonary endarterectomy. Between June 2004 and September 2005, eight
      patients underwent PEA without HCA. We introduced a double venting of the left
      heart sections, utilizing two cannulas placed in the left ventricle and atrium.
      Both vent cannulas are connected with vacuum device to prevent back-bleeding and
      left heart distension from the large amount of bronchial flow. We were able to
      perform pulmonary endarterectomy avoiding circulatory arrest and deep hypothermia
      without sacrificing the effectiveness of the procedure. The initial encouraging
      results have convinced us to apply systematically this technique in the cases
      operated in our center, even though further investigations are necessary to fully
      examine this technique.

PMID- 16884908
TI  - Effect of PEA on LPS inflammatory action in human adipocytes.
AB  - N-Palmitoylethanolamide (PEA) is an endogenous lipid secreted by human adipocytes
      that possesses numerous anti-inflammatory properties. Human adipose tissue can be
      subjected to modulation of its inflammatory state by lipopolysaccharide (LPS).
      Here we demonstrate that LPS increases the secretion of interleukin-6 (IL-6) by
      human mature adipocytes via activation of the NFkappaB pathway. This effect is
      not inhibited by PEA. Inversely, LPS strongly inhibits adipose cell leptin
      release, with PEA acting as a potentiator of this inhibitory effect. These
      actions are not linked to a reduction in leptin gene transcription. Thus, PEA
      does not have an anti-inflammatory role in the secretion of IL-6 via NFkappaB at
      the adipocyte level, but instead seems to act at the heart of the LPS-stimulated
      pathway, which, independently of NFkappaB, inhibits the secretion of leptin.

PMID- 16884909
TI  - In vivo CD4+ T-cell up-regulation and high dose side effects of refolded duck
      interleukin-2.
AB  - The recombinant duck interleukin-2 (rduIL-2) monomer was firstly isolated under
      nature condition, and refolded by oxidization procedure. Refolded rduIL-2 monomer
      induced in vitro proliferation of Con A-stimulated duck splenocytes in a
      sensitive and dose-dependent manner, and up-regulated in vivo the amounts of CD4+
      T cells with low dose of administration. However, high doses intermittent
      administration resulted in sever side effects in vivo, with typical lymphocytic
      interstitial pneumonitis and nephritis, and lymphocytic depletion in splenic
      corpuscle. Our findings might be beneficial to studies of both mechanism and
      applications in vivo of avian IL-2.

PMID- 16884910
TI  - Interferonbeta-induced changes in metallothionein expression and subcellular
      distribution of zinc in HepG2 cells.
AB  - We evaluated the changes of metallothionein induction and cellular zinc
      distribution in HepG2 cells by interferonbeta treatment. Immunohistochemical
      staining of metallothionein was observed in the cytoplasm and nuclei of
      hepatocytes; which was observed predominantly in the cells treated with
      interferon and zinc compared to those with zinc alone, interferon alone or the no
      treated control. The cellular zinc level was higher in order of the interferon-
      and zinc-treated cells, the zinc-alone-treated cells, and the interferon-alone
      treated cells. Flow cytometry showed that S-phase population increased in
      interferon-alone-treated cells and interferon- and zinc-treated cells, but not in
      zinc-alone-treated ones. Cellular elemental distribution was analyzed using in
      air micro-particle induced X-ray emission. In zinc-alone-treated sample, X-ray
      spectra showed good consistency between the enhanced cellular zinc distribution
      and the phosphorous map. Localizations of bromine followed by interferon
      treatment were found accompanying a spatial correlation with the phosphorous map.
      The samples treated with interferon and zinc showed the marked accumulation of
      zinc and bromine. Discrete bromine accumulation sites were clearly visible with a
      strong spatial correlation followed by zinc accumulation. These findings suggest
      that interferonbeta in combination with zinc predominantly induces
      metallothionein expression in HepG2 cells. In addition, interferonbeta may
      promote the translocation of metallothionein-bound zinc from cytoplasm to S-phase
      nuclei.

PMID- 16884911
TI  - Changes in the pro-inflammatory cytokine production and peritoneal macrophage
      function in rats with chronic heart failure.
AB  - Chronic heart failure (CHF) is a state of immune activation, and pro-inflammatory
      cytokines play an important role in its development and progression. Macrophages
      (Mphis), when activated, are the main source of pro-inflammatory cytokines. We
      measured interleukin-6 (IL-6), interleukin (IL-1beta) and tumor necrosis factor -
      alpha (TNF-alpha) production after lipopolysaccharide (LPS)-stimulation, as well
      as peritoneal Mphis migration, phagocytic capacity, chemotaxis index, and
      hydrogen peroxide production, in an attempt to clarify the role of this cell in
      an animal model of CHF. Ligature of the left coronary artery or sham operation
      was performed in adult Wistar rats. After 12 weeks, resident and total cell
      number, phagocytic capacity, chemotaxis index, and hydrogen peroxide production
      in Mphis were significantly higher in CHF than in control rats. The production of
      IL-6 and TNF- alpha was similarly significantly enhanced in CHF as compared with
      controls. Mphis obtained from CHF rats were more responsive to LPS, suggesting
      the existence, in vivo, of possible factor(s) modulating the production of pro
      inflammatory cytokines. The results demonstrated that there is modification of
      peritoneal Mphis function along CHF development, possibly contributing to the
      pathophysiological process in the establishment of CHF.

PMID- 16884912
TI  - Synergistic effect of tumor necrosis factor-alpha and interferon-gamma on
      enterocyte shedding of syndecan-1 and associated decreases in internalization of
      Listeria monocytogenes and Staphylococcus aureus.
AB  - Syndecan-1 is a heparan sulfate proteoglycan expressed on epithelia, and its
      ectodomain can be shed into the extracellular milieu, affecting a variety of
      cellular functions. Using two bacteria known to react with heparan sulfate,
      Listeria monocytogenes and Staphylococcus aureus, experiments were designed to
      clarify the effect of syndecan-1 shedding on bacterial internalization by human
      HT-29 enterocytes. Mature enterocytes were incubated with tumor necrosis factor
      (TNF)-alpha and/or interferon (IFN)-gamma for 16h prior to addition of bacteria.
      These cytokines acted synergistically to decrease syndecan-1 expression, assessed
      by visual observations of syndecan-1 expression on enterocytes using
      immunohistochemistry and a monoclonal antibody to the syndecan-1 core protein, by
      quantifying this fluorescent intensity, and by quantifying the concentration of
      shed syndecan-1 using an enzyme-linked immunoabsorbent assay. Neither IFN-gamma
      nor TNF-alpha alone had a noticeable effect on L. monocytogenes internalization,
      but a mixture of both cytokines resulted in decreased (P<0.01) internalization.
      Enterocyte preincubation with TNF-alpha alone, and with both cytokines, was
      associated with decreased S. aureus internalization, at P<0.05 and P<0.01,
      respectively. Thus, TNF-alpha and IFN-gamma acted synergistically to shed
      syndecan-1 ectodomains from HT-29 enterocytes, and shedding was associated with
      decreased internalization of two pathogenic bacteria, suggesting that syndecan-1
      shedding may modulate the pathogenesis of specific microbes.

PMID- 16884913
TI  - Mice lacking both TNFalpha receptors show increased constitutive expression of
      IFNgamma: a possible reason for lack of protection from fumonisin B1
      hepatotoxicity.
AB  - Fumonisin B1 is a mycotoxin prevalent in corn that produces species-, gender-,
      and organ-specific diseases. Mice lacking TNFalpha receptor (TNFR) 1 or 2
      exhibited a diminished hepatotoxic response to fumonisin B1; however, the
      protection was lost when both TNFRs were deleted. We therefore investigated the
      constitutive expression of selected apoptotic factors and their response to
      fumonisin B1 in the liver from mice lacking both TNFRs (DRKO). Compared to their
      wild-type (WT) counterparts the DRKO strain had a higher constitutive mRNA
      expression of interferon (IFN)gamma, Fas, and interleukin (IL)-18. The mRNA
      expression of Bcl-2 was also higher in DRKO than in WT mice. The mRNA expression
      of IL-1 receptor antagonist (IL-1Ra) was decreased; that of TNF-related apoptosis
      inducing ligand (TRAIL) was dramatically reduced. Induction of most apoptotic
      genes in response to fumonisin B1 was similar in both WT and DRKO strains; except
      in DRKO mice it was greater for Max and lesser for IL-1Ra than that in WT strain.
      Fumonisin B1 hepatotoxicity in DRKO mice was reduced by pretreatment with anti
      IFNgamma antibody. It appears that in the absence of TNFalpha signaling other
      apoptotic pathways become operative; particularly the increase of IFNgamma, Fas
      and IL-18 may compensate for the loss of TNFalpha effects. Fumonisin B1 toxicity
      therefore appears to be a complex phenomenon that may utilize more than one
      cytotoxic pathway consequent to sphingoid deregulation; a higher expression of
      IFNgamma and other apoptotic factors in DRKO may be responsible for the observed
      fumonisin hepatotoxicity.

PMID- 16884914
TI  - Pharmacokinetics of cyclosporine in recipients of marginal versus standard liver
      transplants.
AB  - In the field of transplants, the practice of using marginal donor livers has
      become widely accepted, yielding good clinical results. This study investigated
      and compared the pharmacokinetics of cyclosporine in marginal and standard liver
      transplant recipients. Twenty-four de novo liver transplant patients, 12 with
      marginal and 12 with standard (normal) grafts, were treated with a microemulsion
      formulation of cyclosporine (capsules 100 mg) as immunosuppressive therapy. Blood
      concentration profiles were measured, and pharmacokinetic calculations performed
      at days 3 and 10 after transplantation. Different sampling strategies to predict
      drug exposure (AUC(0-12 h)) were compared, and the best limited-sampling
      strategies to monitor the desired blood levels were determined. Marginal and
      standard patients showed a significant difference in blood concentration and
      pharmacokinetic profiles of cyclosporine at the day 10 post-transplantation.
      Blood concentration at 4h (C(4 h)) was the single best timepoint to estimate
      AUC(0-12 h) in marginal liver transplant (r(2)=0.700), while C(2h) was confirmed
      to be the optimal choice with standard graft (r2=0.720). Two blood samples at 2
      and 6 h significantly improved the prediction model in both groups (r2=0.920).
      Our data suggest that patients receiving a marginal liver transplant present a
      different pharmacokinetic profile of cyclosporine from those receiving standard
      graft, which should be taken into account in dosing the patient to avoid
      subtherapeutic blood concentrations or toxic effects.

PMID- 16884915
TI  - Hyaluronic acid counteracts interleukin-1-induced inhibition of collagen
      biosynthesis in cultured human chondrocytes.
AB  - Although, hyaluronic acid (HA) is used in the treatment of osteoarthritis for 30
      years, the mechanism of its protective action on collagen metabolism disturbances
      in tissues during inflammation is not known. Therefore, the present study was
      undertaken to evaluate the mechanism of IL-1beta action (inductor of experimental
      inflammation) on deregulation of collagen biosynthesis in cultured human
      chondrocytes and the effect of HA on the process. It has been found that IL-1beta
      strongly induced inhibition of collagen biosynthesis, while HA counteracted the
      process. The mechanism of this phenomenon was found at both transcriptional and
      post-transcriptional level. IL-1 was found to down regulate the expression of
      mRNA for type II collagen and to inhibit prolidase activity, an enzyme that plays
      an important role in collagen biosynthesis at post-translational level. HA was
      shown to counteract the IL-1beta-dependent inhibition of both processes. During
      experimental inflammation of chondrocytes cultured in 0.1% FBS there was no
      differences in the expression of beta(1)-integrin independently of cell number
      and the presence of HA in growth medium. In chondrocytes cultured in 5% FBS, IL
      1beta up-regulated the expression of beta(1)-integrin receptor while HA abolished
      the effect. The data suggest that HA-dependent up-regulation of collagen
      biosynthesis in IL-1beta-treated chondrocytes may involve stimulation of
      prolidase activity in serum "starved" cells and may also originate at the
      transcriptional level in the cells cultured in standard conditions.

PMID- 16884916
TI  - Genome-wide location analysis of the stress-activated MAP kinase Hog1 in yeast.
AB  - MAP kinase signal transduction pathways play a critical role in eukaryotic cells
      to unleash complex transcriptional programs to properly adapt to changing
      environments. The MAP kinase Hog1 upon activation is physically recruited to the
      chromatin of osmostress responsive genes. This allowed us to use in vivo
      chromatin immunoprecipitation in combination with microarrays (ChIP-Chip) to
      identify the transcriptional targets of Hog1 at the genomic scale. The ChIP-Chip
      method described here revealed that the stress-activated MAP kinase gets
      recruited to most of the osmoinducible genes. Interestingly Hog1 associates with
      both the 5' upstream and the 3' downstream sequences of stress genes. We
      confirmed by targeted ChIP at several stress genes that the MAP kinase crosslinks
      all over the transcribed regions in all cases tested. Taken together the genome
      wide location analysis reported here is a powerful approach to determine the
      genomic binding patterns of an activated MAP kinase and will be of great interest
      to analyze other SAPKs under different environmental conditions.

PMID- 16884918
TI  - Functional analysis of protein kinase networks in living cells: beyond "knock
      outs" and "knock-downs".
AB  - The identification of over 500 protein kinases encoded by the human genome
      sequence offers one measure of the importance of protein kinase networks in cell
      biology. High throughput technologies for inactivating genes are producing an awe
      inspiring amount of data on the cellular and organismal effects of reducing the
      levels of individual protein kinases. Despite these technical advances, our
      understanding of kinase networks remains imprecise. Major challenges include
      correctly assigning kinases to particular networks, understanding how they are
      regulated, and identifying the relevant in vivo substrates. Genetic methods
      provide a way of addressing these questions, but their application requires
      understanding the nuances of how different types of mutations can affect protein
      kinases. The goal of this article is to provide a brief introductory primer into
      these issues using examples from yeast MAPK cascades and to motivate future
      systematic genetic analysis focusing on individual residues of protein kinases.

PMID- 16884917
TI  - Analysis of mitogen-activated protein kinase activation and interactions with
      regulators and substrates.
AB  - Mitogen-activated protein kinase (MAPK) cascades are ubiquitous signal
      transduction modules in eukaryotes that are of great interest and importance.
      Here, we summarize some useful methods for the analysis of MAPK signaling,
      including methods to (1) detect MAPK activation in cells, with an emphasis on
      using phosphorylation-state-specific antibodies raised against mammalian
      phosphopeptide sequences to detect the activation of MAPKs in other species; (2)
      estimate the cellular concentrations of MAPKs and other proteins of interest; (3)
      detect and quantify the stable physical association of MAPKs with their
      substrates and regulators, and estimate the relevant dissociation constants; (4)
      delineate the MAPK-binding regions or domains of MAPK-interacting proteins, with
      particular emphasis on the identification and verification of MAPK-docking sites.
      These procedures are broadly applicable to many organisms, including both yeast
      and mammalian cells.

PMID- 16884919
TI  - Capturing protein-protein complexes at equilibrium: the holdup comparative
      chromatographic retention assay.
AB  - The popular pulldown chromatographic assay detects complexes mediated by fusion
      proteins retained on affinity resin. The main limitation of this method is that
      it does not analyze complexes at equilibrium but after several washing steps.
      Consequently, fast-dissociating complexes may remain undetected. Here, we present
      the holdup assay, based on the principle of comparative chromatographic retention
      which eliminates the use of washing steps. The assay evaluates fractions of free
      and bound species at equilibrium. We used human papillomavirus oncoprotein E6, an
      E6-binding peptide and an E6-binding PDZ domain, to test several protocols
      utilizing pure proteins or expression extracts. The holdup assay is faster and
      more informative than the pulldown assay. It detects fast-dissociating complexes
      and it is also suited for evaluating equilibrium constants. It is potentially
      adaptable for automated determination of affinity constants and high-throughput
      analysis of interactions between proteins and other proteins, peptides, nucleic
      acids, or small regulatory molecules.

PMID- 16884920
TI  - Production and characterization of clinical grade Escherichia coli derived
      Plasmodium falciparum 42 kDa merozoite surface protein 1 (MSP1(42)) in the
      absence of an affinity tag.
AB  - The 42 kDa cleavage product from the carboxyl end of the Plasmodium falciparum
      merozoite surface protein 1 (MSP1(42)) is an important blood-stage malaria
      vaccine target. Several recombinant protein expression systems have been used for
      production of MSP1(42) including yeast (Saccharomyces cerevisiae and Pichia
      pastoris), Escherichia coli, baculovirus and transgenic animals. To date, all of
      the reported recombinant proteins include a 6 x His affinity tag to facilitate
      purification, including three MSP1(42) clinical grade proteins currently in human
      trials. Under some circumstances, the presence of the 6 x His tag may not be
      desirable. Therefore, we were interested to produce clinical grade MSP1(42)
      without a 6 x His affinity tag from E. coli inclusion bodies. We produced a
      recombinant MSP1(42) with a P. falciparum FUP (Uganda-Palo Alto) phenotype which
      accounts for a substantial proportion of the MSP1(42) protein observed in African
      isolates. EcMSP1(42)-FUP was produced in E. coli inclusion bodies by high cell
      mass induction with IPTG using 5 L and 60 L bioreactors. Isolated inclusion
      bodies were solubilized in 8M guanidine-HCl and the EcMSP1(42)-FUP protein
      refolded by rapid dilution. Refolded EcMSP1(42)-FUP was purified using
      hydrophobic interaction chromatography, anion exchange chromatography, and size
      exclusion chromatography, and subject to biochemical characterization for
      integrity, identity, and purity. Endotoxin and host cell protein levels were
      within acceptable limits for human use. The process was successfully transferred
      to pilot-scale production in a cGMP environment. A final recovery of 87.8 mg of
      clinical-grade material per liter of fermentation broth was achieved. The
      EcMSP1(42)-FUP clinical antigen is available for preclinical evaluation and human
      studies.

PMID- 16884921
TI  - High-level expression and characterization of Galactomyces geotrichum (BT107)
      lipase I in Pichia pastoris.
AB  - The mature lipI gene, encoding the lipase I from Galactomyces geotrichum BT107,
      was obtained by PCR from genomic DNA, sequenced and cloned into a Pichia pastoris
      expression vector. Clones containing multiple copies of lipI integrated in their
      genome were analyzed to achieve high-level expression of the recombinant lipase
      I. One strain with four or more copies of the expression cassette was able to
      produce more than 200mg/L of extracellular heterologous protein. The lipase I was
      partially purified using anion exchange chromatography and its activity on
      monounsaturated (triolein) and polyunsaturated (triEPA) triglycerides was
      analyzed by a novel HPLC-MS assay.

PMID- 16884922
TI  - Elimination of in vivo cleavage between target protein and intein in the intein
      mediated protein purification systems.
AB  - IMPACT is a novel protein purification system developed by New England BioLabs.
      This system utilizes the inducible self-cleavage activity of a protein splicing
      element (termed intein) to separate the target protein from the affinity intein
      CBD tag without using any proteases. The IMPACT system has been widely used as an
      easy, one-step protein purification procedure. However, IMPACT usually produces a
      lower target protein yield than other protein purification systems, such as the
      pET system. It was found that the lower yield of the target protein, in many
      cases, was due to in vivo cleavage between the target protein and the intein
      during protein expression. Self-cleavage requires the first residue of the intein
      to be a cysteine with a free sulfhydryl group. In order to eliminate this in vivo
      auto-cleavage, we designed two single cysteine mutants in the intein protein to
      allow potential disulfide bond formation with the first cysteine. Therefore, no
      free sulfhydryl group in the first cysteine of the intein is available during
      protein expression. Our data indicated that the in vivo auto-cleavage during
      bacterial expression was completely eliminated with the intein mutation,
      resulting in a significant enhancement of the protein yield of the IMPACT
      expression system, comparable to the other high-level expression systems.

PMID- 16884923
TI  - Purification, crystallization and preliminary X-ray diffraction analysis of the
      phage T4 vertex protein gp24 and its mutant forms.
AB  - The study of bacteriophage T4 assembly has revealed regulatory mechanisms
      pertinent not only to viruses but also to macromolecular complexes. The capsid of
      bacteriophage T4 is composed of the major capsid protein gp23, and a minor capsid
      protein gp24, which is arranged as pentamers at the vertices of the capsid. In
      this study the T4 capsid protein gp24 and its mutant forms were overexpressed and
      purified to homogeneity. The overexpression from plasmid vectors of all the
      constructs in Escherichia coli yields biologically active protein in vivo as
      determined by assembly of active virus following infection with inactivated gene
      24 mutant viruses. The gp24 mutant was subjected to surface entropy reduction by
      mutagenesis and reductive alkylation in order to improve its crystallization
      properties and diffraction quality. To determine if surface mutagenesis targeting
      would result in diffractable crystals, two glutamate to alanine mutations
      (E89A,E90A) were introduced. We report here the biochemical observations and
      consequent mutagenesis experiment that resulted in improvements in the stability,
      crystallizability and crystal quality of gp24 without affecting the overall
      folding. Rational modification of the protein surface to achieve crystallization
      appears promising for improving crystallization behavior and crystal diffracting
      qualities. The crystal of gp24(E89A,E90A) diffracted to 2.6A resolution compared
      to wild-type gp24 at 3.80A resolution under the same experimental conditions.
      Surface mutation proved to be a better method than reductive methylation for
      improving diffraction quality of the gp24 crystals.

PMID- 16884924
TI  - The three-dimensional structure of an eukaryotic glutamine synthetase: functional
      implications of its oligomeric structure.
AB  - The structure of the prokaryotic glutamine synthetases type I (GS-I), key enzymes
      in nitrogen metabolism, was determined several years ago by X-ray diffraction,
      and consists of a double hexameric ring. The structure of the eukaryotic GS from
      the plant Phaseolus vulgaris (Glutamine synthetase type II; GS-II) has now been
      determined at low-resolution using electron microscopy and image processing, and
      consists of an octamer composed of two tetramers placed back-to-back and rotated
      90 degrees with respect to each other. The oligomeric structure possesses a
      twofold symmetry, very suggestive of each tetramer being composed of two dimers.
      This is reinforced by the fact that dimers are isolated as a stable albeit non
      functional species during the purification procedure. Given the fact that the
      active site of all types of GS is formed by highly conserved residues located in
      the interface of two interacting monomers, the geometry of the reconstructed
      tetramer suggests that it only contains two functional active sites, i.e., an
      active site per dimer. This is supported by biochemical data, which reveal that
      while the octamer binds eight ATP molecules, it only binds four molecules of the
      transition state analogue and GS inhibitor methionine-(S)-sulfoximine-P (MetSox
      P). All this suggests for the GS-II enzyme an oligomeric structure containing
      four active sites and four possible regulatory sites, which might point to a
      complex regulatory behavior.

PMID- 16884925
TI  - Structural correlations in the family of small leucine-rich repeat proteins and
      proteoglycans.
AB  - The family of small leucine-rich repeat proteins and proteoglycans (SLRPs)
      contains several extracellular matrix molecules that are structurally related by
      a protein core composed of leucine-rich repeats (LRRs) flanked by two conserved
      cysteine-rich regions. The small proteoglycan decorin is the archetypal SLRP.
      Decorin is present in a variety of connective tissues, typically "decorating"
      collagen fibrils, and is involved in important biological functions, including
      the regulation of the assembly of fibrillar collagens and modulation of cell
      adhesion. Several SLRPs are known to regulate collagen fibrillogenesis and there
      is evidence that they may share other biological functions. We have recently
      determined the crystal structure of the protein core of decorin, the first such
      determination of a member of the SLRP family. This structure has highlighted
      several correlations: (1) SLRPs have similar internal repeat structures; (2) SLRP
      molecules are far less curved than an early model of decorin based on the three
      dimensional structure of ribonuclease inhibitor; (3) the N-terminal and C
      terminal cysteine-rich regions are conserved capping motifs. Furthermore, the
      structure shows that decorin dimerizes through the concave surface of its LRR
      domain, which has been implicated previously in its interaction with collagen. We
      have established that both decorin and opticin, another SLRP, form stable dimers
      in solution. Conservation of residues involved in decorin dimerization suggests
      that the mode of dimerization for other SLRPs will be similar. Taken together
      these results suggest the need for reevaluation of currently accepted models of
      SLRP interaction with their ligands.

PMID- 16884926
TI  - Refined structure of bony fish muscle myosin filaments from low-angle X-ray
      diffraction data.
AB  - Application of X-ray diffraction methods to the elucidation of the arrangement of
      the myosin heads on myosin filaments in resting muscles is made simpler when the
      muscles themselves are well ordered in 3D. Bony fish muscle for the vertebrates
      and insect flight muscle for the invertebrates are the muscles of choice for this
      analysis. The rich, well-sampled, low-angle X-ray diffraction pattern from bony
      fish muscle has previously been modelled with an R-factor of 3.4% between
      observed and calculated transforms on the assumption that the two heads in one
      myosin molecule have the same shape. However, recent evidence from other kinds of
      analysis of other muscles has shown that this assumption may not be valid. There
      is evidence that the motor domain of one head in each pair may interact with the
      neck region of the second head. This possibility has been tested directly in the
      present analysis which extends the X-ray modelling of fish muscle myosin
      filaments by permitting independent shape changes of the two heads in one
      molecule. The new model, with a computed R-factor of 1.19% against 56 independent
      reflections, shows that in fish muscle also there is a marked asymmetry in the
      organisation of each head pair.

PMID- 16884927
TI  - COMT genotype predicts BOLD signal and noise characteristics in prefrontal
      circuits.
AB  - OBJECTIVE: Prefrontal dopamine (DA) is catabolized by the COMT (catechol-O
      methyltransferase) enzyme. Literature suggests that the Val/Met single nucleotide
      polymorphism (SNP) in the COMT gene predicts executive cognition in humans with
      Val carriers showing poorer performance due to less available synaptic DA. Recent
      fMRI studies are thought to agree with these studies having demonstrated
      prefrontal hyperactivation during n-back and attention-requiring tasks. This was
      interpreted as "less efficient" processing due to impaired signal-to-noise ratio
      (SNR) of neuronal activity. However, electrophysiological studies of neuronal SNR
      in primates and humans imply that prefrontal cortex should show a diminished
      prefrontal BOLD response in Val carriers. In the present study, we addressed the
      question of whether the prefrontal SNR of the BOLD response is decreased in Val
      carriers using a visual oddball task and an approach to analysis of fMRI data
      that maximizes noise characterization. METHODS: We investigated N=17 homozygous
      Met carriers compared with N=24 Val carriers matched for age, sex, education, IQ,
      reaction time (variability) and head motion. Event-related fMRI was conducted
      presenting 160 visual stimuli (40 targets, checkerboard reversal). Subjects had
      to respond as quickly as possible to targets by button press. In the fMRI GLM
      [y(t)=beta*x(t)+c+e(t)] analysis, voxel-by-voxel 'activation' [y(t)] as well as
      residual noise variance [e(t)=sigma2] were calculated using a conservative full
      width half maximum (FWHM=6 mm). RESULTS: As compared to Val carriers, we observed
      a stronger and more extended BOLD responses in homozygous Met carriers in left
      supplementary motor area (SMA) extending to ACC and dorsolateral prefrontal
      cortex. Vice versa, increased levels of noise were seen in Val carriers
      surrounding the peak activation maximum. DISCUSSION: In line with our
      expectations from prior electrophysiological studies, we observed a diminished
      BOLD response and increased noise in Val carriers. This suggests that the DA
      stabilizes cortical microcircuits by sharpening the signal and suppressing
      surrounding noise.

PMID- 16884928
TI  - Magnetoencephalographic study of vibrotactile evoked transient and steady-state
      responses in human somatosensory cortex.
AB  - Somatosensory responses to vibrotactile stimulation applied to the index
      fingertip were recorded with whole-head MEG in eleven healthy young adult
      participants. Stimulus trains were produced by a pneumatically driven membrane
      oscillating at 22 Hz for a trial duration of 1 s, separated by interstimulus
      intervals (ISIs) of 0.5, 1.0, 3.0, and 7.0 s. Data analysis was performed in two
      frequency bands. Transient onset responses in the lower frequency band (<20 Hz)
      contained a clearly expressed P50 component. The higher frequency band (18-30 Hz)
      revealed a gamma-band response (GBR) within the first 200 ms followed by rhythmic
      activity at the stimulus frequency that continued throughout the stimulus
      duration, known as the steady-state response (SSR). Dipoles associated with the
      transient responses and SSRs were localized in two distinct regions within the
      primary somatosensory cortex (SI), with transient responses located on average 3
      mm more medial and inferior than the SSRs. The transient and GBR peak amplitudes
      increased with ISI, whereas the SSR amplitude showed no ISI dependence. These
      results may reflect functionally and spatially distinct neural populations.
      Further investigations are required to assess the implications of these findings
      for probing the somatosensory system using other functional neuroimaging methods
      such as fMRI.

PMID- 16884929
TI  - In vivo detection of gray and white matter differences in GABA concentration in
      the human brain.
AB  - A novel selective multiple quantum filtering-based chemical shift imaging method
      was developed for acquiring GABA images in the human brain at 3 T. This method
      allows a concomitant acquisition of an interleaved total creatine image with the
      same spatial resolution. Using T(1)-based image segmentation and a nonlinear
      least square regression analysis of GABA-to-total creatine concentration ratios
      in frontal and parietal lobes of healthy adult volunteers as a function of the
      tissue gray matter fraction, the mean GABA concentration in gray and white matter
      was determined to be 1.30+/-0.36 micromol/g and 0.16+/-0.16 micromol/g (mean+/
      SD, n=13), respectively. It is expected that this method will become a useful
      tool for studying GABAergic function in the human brain in vivo.

PMID- 16884930
TI  - A comparison of seizure outcome after callosotomy in patients with Lennox-Gastaut
      syndrome and a positive or negative history for West syndrome.
AB  - PURPOSE: This retrospective study was designed to clarify the role of West
      syndrome in post-callosotomy seizure outcome in patients with Lennox-Gastaut
      syndrome. METHODS: From September 1989 to May 1999, 74 patients diagnosed with
      Lennox-Gastaut syndrome received anterior corpus callosotomy at Taipei Veterans
      General Hospital, Taiwan. All patients were followed for more than 4 years after
      surgery. Among them, 21 (28.4%) patients had a history of West syndrome (Group A)
      whereas 53 (71.6%) patients did not have a history of West syndrome (Group B).
      Postoperative seizure outcome was compared for these two patient groups. RESULTS:
      A total of 16 (76.2%) patients in Group A (positive history) and 29 (54.7%)
      patients in group B (negative history) achieved significant improvement in
      seizures after surgery (e.g., seizure reduction of more than 50%). There was no
      statistical significance (p=0.088) in the difference in outcome between the two
      groups. CONCLUSIONS: A history of West syndrome does not appear to influence post
      callosotomy seizure outcome in patients with Lennox-Gastaut syndrome.

PMID- 16884931
TI  - Activation of bone marrow cells treated with Canova in vitro.
AB  - Canova is a Brazilian complex homeopathic medication produced from Aconitum,
      Thuya, Bryonia, Lachesis and Arsenicum. Previous studies demonstrated that Canova
      induces up-regulation in numbers of leukocytes. The bone marrow microenvironment
      is composed of growth factors, stromal cells, extracellular matrix, and
      progenitor cells that differentiate into mature blood cells. As it is the major
      site of blood cell formation, we studied in vitro Canova effects on bone marrow
      cells of mice. Swiss mouse femurs were dissected, cleaned, and the marrow was
      flushed. The cells were plated, treated or not, incubated for different times and
      processed for light, scanning electron, and confocal microscopy, and also flow
      cytometry. The treatment did not modify the expression of the analyzed surface
      markers or cytokine production. All microscopy techniques showed that a monocytic
      lineage (CD11b(+)) and stromal cells (adherent cells) were activated by
      treatment. Canova also increased cell clusters over adherent cells, suggesting
      proliferation areas.

PMID- 16884932
TI  - Endogenous cortisol level interacts with noradrenergic activation in the human
      amygdala.
AB  - Animal studies show that high cortisol levels exert their effect on stressful
      task performance via modulation of the amygdala. Availability of noradrenaline in
      this brain region appears to be a critical prerequisite for this effect. This
      relationship between noradrenaline and cortisol is explained by an animal model
      where the amygdala constitutes a crucial region for this interaction. In humans
      this model has not been extensively tested so far. In a previously reported study
      human subjects (aged 20.93+/-2.38) were scanned using fMRI when watching sets of
      emotional and neutral pictures after taking the beta-adrenergic antagonist
      propranolol or placebo. Stimulus sets consisted of 92 pictures, divided in four
      emotional categories that ranged from neutral scenes of domestic objects (CAT1)
      to extremely negative scenes of mutilation or accidents (CAT4). Confrontation
      with arousing emotional pictures, accompanied by increased noradrenaline levels,
      evoked increased amygdala activation under placebo but not under betablocker
      condition. This new and additional analysis of this data set was carried out to
      determine the effect of differential endogenous cortisol levels on amygdala
      activation. Cortisol levels during scanning were determined using salivary
      samples and subjects were post hoc divided in a High (n=14) and Low cortisol
      group (n=14). When subjects were watching emotional stimuli, presumably
      associated with enhanced noradrenaline (NA) levels, amygdala activation was
      contrasted between the two cortisol groups. We hypothesized that emotional
      stimuli would elicit more amygdala activation in the High than in the Low
      cortisol group. Here we demonstrate indeed a significant interaction effect of
      the endogenous cortisol level with increasing activation in the amygdala under
      placebo but not under betablocker condition, thereby extending the rodent based
      model of a synergistic effect of the two stress hormones to the human.

PMID- 16884933
TI  - Identification of Gnr1p, a negative regulator of G alpha signalling in
      Schizosaccharomyces pombe, and its complementation by human G beta subunits.
AB  - G protein-coupled receptors (GPCRs) are involved in the response of eukaryotic
      cells to a wide variety of stimuli, traditionally mediating their effects through
      heterotrimeric G proteins comprised of G alpha, G beta and G gamma subunits. The
      fission yeast Schizosaccharomyces pombe is an established tool for GPCR research,
      possessing two G alpha-dependent signalling cascades. A complete G alpha beta
      gamma complex has been characterised for the glucose-sensing pathway, but only
      the G alpha subunit, Gpa1p, has been identified in the pheromone-response
      pathway. Here, we report the use of the yeast two-hybrid system to identify a
      novel protein, Gnr1p, which interacts with Gpa1p. Gnr1p is predicted to contain
      seven WD repeats and to adopt a structure similar to typical G beta subunits.
      Disruption and overexpression studies reveal that Gnr1p negatively regulates the
      pheromone-response pathway but is not required for signalling. Human G beta
      subunits complement the loss of Gnr1p, functioning as negative regulators of G
      alpha signalling in fission yeast.

PMID- 16884935
TI  - Assessment of clinical criteria to diagnose scrapie in Italy.
AB  - A reliable ante-mortem test for the detection of scrapie in all genotypes has not
      yet been developed and clinical diagnosis remains a useful tool for surveillance
      purposes. This paper describes the results of a three-year study in which
      clinical signs consistent with scrapie were recorded according to standardized
      criteria in 245 sheep from 21 outbreaks in Italy in order to identify helpful
      criteria for the diagnosis of the disease. Thirty-seven sheep were scrapie
      positive at post-mortem rapid testing, 23 showed weight loss, 20 had
      proprioceptive deficits, 17 demonstrated ataxia and nibble reflex, and some sheep
      had a combination of signs. Six scrapie-positive sheep were asymptomatic. The
      clinical protocol was easy to handle and appears to be a useful tool for
      improving passive surveillance. The data suggested that positive clinical
      history, nibble, and nibble combined with proprioceptive positioning deficit have
      a quite high negative predictive value. The protocol will be proposed as a tool
      for field inspection in passive surveillance in Italy.

PMID- 16884934
TI  - Role of nitric oxide in the inhibition of liver cytochrome P450 during sepsis.
AB  - Nitric oxide (NO) plays an important role in the pathophysiology of sepsis and
      septic shock but the mechanism is not well understood. The aim of this study was
      to investigate the role of NO in the cytochrome P450 (CYP) isozyme activity and
      the expression of its gene during polymicrobial sepsis. The rats were subjected
      to polymicrobial sepsis by cecal ligation and puncture (CLP). Aminoguanidine (AG,
      100 mg/kg body weight) or N(omega)-nitro-L-arginine methyl ester (L-NAME, 100
      mg/kg body weight) was injected intraperitoneally at 0, 3, 6, 10, and 20 h after
      CLP. The plasma nitrite/nitrate concentration increased 24 h after CLP, and this
      increase was almost completely abolished by AG and L-NAME. Sepsis increased the
      serum aminotransferase and lipid peroxidation levels, which were attenuated by AG
      but augmented by L-NAME. The hepatic concentration of the reduced gluthathione
      decreased in the CLP rats, which was inhibited by AG but augmented by L-NAME. The
      total CYP content decreased after CLP, which was restored by AG and L-NAME. The
      CYP1A1, 1A2, and 2E1 activities, along with their protein levels, decreased 24 h
      after CLP but these decreases were reversed by AG and L-NAME. The CYP1A1, 1A2,
      2B1, and 2E1 mRNA expression levels decreased 24 h after CLP, and L-NAME
      inhibited this decrease. NO plays a key role in the sepsis-mediated decrease in
      CYP via the interplay of two different mechanisms: NO-dependent suppression of
      protein via the enhanced inducible NO synthase, and NO-dependent transcriptional
      suppression via endothelial NO synthase.

PMID- 16884937
TI  - Field propagation phenomena in ultra high field NMR: a Maxwell-Bloch formulation.
AB  - The principal advantage of NMR at high field is the concomitant increase in
      signal-to-noise ratio (SNR). This can be traded for improved spatial resolution
      and combined with parallel imaging to achieve higher temporal resolution. At high
      field strength, the RF-wavelength and the dimension of the human body complicate
      the development of NMR coils. For example, at 7 T, the wavelength in free space
      corresponds to about 1m. The dielectric constant in tissue with a high water
      content can be as high as 70 and at a larmor frequency of 300 MHz, this
      corresponds to a wavelength inside tissue of less than 15 cm. The operating
      wavelength is thus comparable to the diameter of most body parts. To this end,
      both temporal and spatial variations of the excitation field must be taken into
      account in addition to the expected increase in conductivity. For all these
      reasons, we find the propagation of radiation at ultra high fields (>4 T) new
      phenomena commonly observed in quantum optics but traditionally negligible in NMR
      such as phase modulation of the excitation field such that the identity between
      pulse area and flip angle is no longer valid. In this paper, the emergence of
      field propagation phenomena in NMR experiments is analytically and numerically
      demonstrated. It is shown that in addition to the well-studied dielectric
      resonance phenomena at high magnetic fields (>4 T), field propagation effects
      transform the excitation pulse into an adiabatic excitation. The high field
      strength also mean that nonlinear effects such as self-induced transparency are
      now possible in NMR experiments.

PMID- 16884936
TI  - Evaluation of FOXC2 as a candidate gene for chronic progressive lymphedema in
      draft horses.
AB  - Chronic progressive lymphedema (CPL) is a debilitating condition identified in
      Clydesdales, Shires and Belgian draft horses and results in progressive swelling
      of the lower legs associated with the development of thick skin folds,
      ulcerations, fibrosis and marked hyperkeratosis. The result is severe discomfort
      and recurrent secondary infection, often requiring euthanasia. Due to the delayed
      onset, many horses are bred prior to diagnosis. CPL has only been documented in
      three related draft horse breeds, suggesting a genetic cause. Determining the
      molecular basis would enable owners to test horses prior to breeding and
      facilitate the elimination of CPL. Mutations in the FOXC2 gene cause a comparable
      condition in humans, lymphedema-distichiasis. This gene was sequenced in affected
      and unaffected draft horses and a control horse. Four single nucleotide
      polymorphisms (SNPs) were identified in unaffected draft horses and the control
      horse, indicating that they were not associated with CPL. A fifth SNP was seen in
      a single affected draft horse and the control horse. Since it was not seen in all
      affected draft horses, this SNP is not associated with the CPL phenotype.

PMID- 16884938
TI  - Investigation of Bi-2223 high temperature superconducting tape as the material
      for gradient coil in MRI.
AB  - The use of Bi-2223 high temperature superconducting (HTS) tape as a material for
      gradient coils in MRI is evaluated in this paper. Bi-2223 tapes have a very high
      critical current and a very low power loss. A HTS tape gradient coil is expected
      to provide much higher gradient strength and generate much lower heating than a
      copper coil. Measurements of the AC power loss of Bi-2223 tapes at typical
      operating frequencies for gradient coils are presented. The degradation of the
      critical current and its effect on the increase of AC power loss is analyzed.
      Practical technical issues such as resistance, gradient strength and mechanical
      performance are also discussed. A prototype Bi-2223 HTS tape gradient coil is
      evaluated to verify the concept.

PMID- 16884939
TI  - Long-lived nuclear spin states in the solution NMR of four-spin systems.
AB  - The existence of long-lived nuclear spin states in four-spin systems is explored
      by solution-state NMR experiments. Long-lived states are proved to exist in three
      different natural product molecules, each containing either a AA'BB' or a AA'XX'
      proton spin system. The measured state lifetimes are between four and eight times
      the spin-lattice relaxation time constants.

PMID- 16884940
TI  - Clinical application of image-guided radiotherapy, IGRT (on the Varian OBI
      platform).
AB  - Image-guided radiation therapy (IGRT) can be used to measure and correct
      positional errors for target and critical structures immediately prior to or
      during treatment delivery. Some of the most recent available methods applied for
      target localization are: transabdominal ultrasound, implanted markers with in
      room MV or kV X-rays, optical surface tracking systems, implantable
      electromagnetic markers, in room CT such as kVCT on rail, kilovoltage or
      megavoltage cone-beam CT (CBCT) and helical megavoltage CT. The verification of
      the accurate treatment position in conjunction with detailed anatomical
      information before every fraction can be essential for the outcome of the
      treatment. In this paper we present the on-board imager (OBI, Varian Medical
      Systems, Palo Alto, CA) that has been in routine clinical use at the Karolinska
      University Hospital since June 2004. The OBI has been used for on-line set-up
      correction of prostate patients using internal gold markers. Displacements of
      these markers can be monitored radiographically during the treatment course and
      the registered marker shifts act as a surrogate for prostate motion. For this
      purpose, on-board kV-kV seems to be an ideal system in terms of image quality.
      The CBCT function of OBI was installed in March 2005 at our department. It
      focuses on localizing tumors based on internal anatomy, not just on the
      conventional external marks or tattoos. The CBCT system provides the capacity for
      soft tissue imaging in the treatment position and real-time radiographic
      monitoring during treatment delivery.

PMID- 16884941
TI  - [Innovation in gynaecological brachytherapy: new technologies, pulse dose-rate
      brachytherapy, image, definition of new volumes of interest and their impact on
      dosimetry: application in a clinical research programme "STIC"].
AB  - Brachytherapy plays a fundamental role in the therapeutic approach of patients
      with stage I-IV cervical carcinoma. Technical modalities have evolved during the
      last decades: stepping source technology, imaging modalities development,
      specially IMN, treatment planning system integrating 3D images. Images from CT
      Scan and MRI have contributed to a better knowledge of tumoral extension and
      critical organs. CT and/or MRI compatible applicators allow a sectional image
      based approach with a better definition of tumour volume compared to traditional
      approaches. The introduction of 3D image based approach for GTV and CTV requires
      new definitions and a common language. In 2000, a working group within GEC-ESTRO
      was created to support 3D image based 3D treatment planning approach in cervix
      cancer BT. The task was to determine a common terminology enabling various groups
      to use a common language. Recommendations were described and proposed based on
      clinical experience and dosimetric concepts of different institutions. Two CTVs
      were described en relation to the risk for recurrence: high-risk CTV and
      intermediate risk CTV. In order to better define the role of such definitions and
      their potential impact on the complication incidence in patients with cervical
      cancer, a special French programme was developed. The aim of this programme is to
      study the incidence of the severe 2-year complication rate in two comparable
      patient populations: one population is treated using PDR brachytherapy with CT
      Scan or MRI with the applicators in place allowing a 3D dosimetry with
      optimization, the second population is treated using standard X-rays radiographs
      without any delineation of the target nor optimisation. Each population arm
      includes 425 patients. A medicoeconomic assessment is performed, allowing a real
      cost of the most sophisticated approach compared to a historical dosimetric
      system.

PMID- 16884942
TI  - [Pregnancy and birth experiences in 12 women undergoing IVF].
AB  - OBJECTIVE: Medical interventions during the perinatal period are psychologically
      difficult for women and research has shown this is true as well for in-vitro
      fertilization procedures (IVF). This study examined the impact of IVF and
      different medical interventions, common to both non-pathological pregnancies and
      IVF, through the analysis of both quantitative and qualitative data. PATIENTS AND
      METHODS: Twelve women undergoing IVF evaluated their experience of pregnancy and
      birth using measures of post-partum depression, maternal self-esteem, and semi
      directive interviews. RESULTS: The results showed that the number of medical
      interventions is correlated with higher scores of post-partum depression as well
      as lowered scores in maternal self-esteem. Qualitative analyses of interviews
      showed that IVF has a complex and unique psychological impact. DISCUSSION AND
      CONCLUSION: The results of this study underline the need for specific
      psychological support for women undergoing IVF treatment.

PMID- 16884943
TI  - In vitro anti-mutagenic effect of magnolol against direct and indirect mutagens.
AB  - Magnolol, a component of the bark of Magnolia obovata, has been reported to
      possess various biological activities, such as anti-carcinogenicity, anti
      promotion activity and anti-oxidative activity. These findings suggest potential
      for this compound in cancer chemoprevention. Interestingly, there have been no
      reports to date on the potential anti-mutagenic activity of magnolol, involving
      inhibition of initiation processes of the primary stage of carcinogenicity. In
      this study, anti-mutagenic activity of magnolol against mutagenicity induced by
      direct mutagens [1-nitropyrene (1-NP), N-methyl-N'-nitro-N-nitrosoguanidine
      (MNNG) and N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG)] and indirect mutagens [2
      amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-aminodipyrido[1,2-a:3',2'
      d]imidazole (Glu-P-2), benzo(a)pyrene (B(a)P), 2-aminoanthracene (2-AA) and 7,12
      dimethylbenz[a]anthracene (DMBA)] were investigated using the bacterial
      mutagenicity test (Ames test). Results show that magnolol strongly inhibits
      mutagenicity induced by indirect mutagens, but does not affect direct mutagens.
      To elucidate the mechanism of this effect against indirect mutagens, effect of
      magnolol on CYP1A1- and CYP1A2-related enzyme activities of ethoxyresorufin-O
      deethylase (EROD) and methoxyresorufin-O-demethylase (MROD) were investigated.
      Magnolol strongly and competitively suppressed these enzyme activities,
      suggesting it inhibited mutation induced by indirect mutagens through suppression
      of CYP1A1 and CYP1A2 activity.

PMID- 16884944
TI  - Remembering the basics: administrative technology and nursing care in a hospital
      emergency department.
AB  - This article discusses findings from qualitative research conducted with nurses
      in a hospital Emergency Department. It explores nurses' attitudes towards a
      patient care information system (PCIS) installed by hospital management in an
      effort to improve patient care through more effective "data sharing". Nurses'
      definitions of care are examined vis-a-vis their perceptions of administrative
      tasks and technologies like the PCIS. Efforts are made to link the system with
      wider patterns of administrative technology acquisition in health care and users'
      everyday/night experiences of using these technologies. The article also presents
      key themes from a literature review of recent case studies about information
      technology implementation in nursing. Results show that nurses choose to define
      care in a way that highlights relationship building and physical/emotional
      connectedness between nurse and patient. The article contends that nurses'
      refusal to incorporate technology-enabled "data sharing" into their definitions
      of care is indicative of efforts to make visible their caring work, often
      rendered invisible by the feminization of care. The article concludes by
      reaffirming the importance of 'remembering the basics', i.e., patient care is
      rooted in the skilled practice of individual caregivers, not in data sharing.

PMID- 16884945
TI  - Case of adult genotype C HBV carrier after acute hepatitis B, losing HBsAg and
      acquiring HBsAb after IFN and lamivudine treatment.
AB  - Here we report the case of a 48-year-old man, carrier of genotype C HBV for
      longer than 6 months after contracting sexually transmitted acute hepatitis B,
      who eventually lost HBsAg and acquired HBsAb by IFN/lamivudine therapy. The
      patient had been negative for HBsAg in 2001, but, during his stay in China from
      January to July in 2003, he developed acute hepatitis B after having an extra
      marital sexual contact there. HBsAg was still positive and a liver biopsy
      indicated chronic hepatitis when he was admitted to our hospital in December 2003
      for detailed examination of liver dysfunction. HBV DNA in his serum, revealed to
      segregate to genotype C by sequencing on admission, decreased to undetectable
      levels at the end of a 3-month IFN therapy, and remained undetectable during and
      after the successive 6-month lamivudine therapy. HBeAg seroconverted to HBeAb
      during the therapy, and HBsAb appeared after the therapy. To our knowledge, this
      is the first case of genotype C chronic hepatitis B occurring after acute
      hepatitis.

PMID- 16884946
TI  - Routes of infection and clinical outcome of Mexican women reactive to anti
      hepatitis C virus antibodies.
AB  - BACKGROUND: Risk factors for the hepatitis C virus (HCV) infection influence both
      the frequency and the progression of the liver disease. Routes of transmission
      and severity of the liver damage may differ by gender. We aimed to describe the
      risk factors for HCV infection and for the severity of the liver disease among
      women seroreactive to anti-HCV antibodies. Also, we tested the hypothesis that
      length of infection influences the levels of anti-HCV, in transfusion-associated
      hepatitis C. METHODS: Eighty-six interferon-naive women, repeatedly seroreactive
      to anti-HCV antibodies, aged>20 years, were studied. RESULTS: Surgeries (80%) and
      transfusion before 1993 (58%) were the main risk factors (52% cases had both).
      The main reason for practicing surgery was obstetric/gynecologic (74%). The main
      indication for transfusion was also obstetric/gynecologic (68%). Fifty-five (64%)
      women were positive to HCV RNA in serum, of them, coinfection with the hepatitis
      B virus (HBV) occurred in three (5%) cases, being occult hepatitis B (i.e.,
      positive to HBV DNA, but negative to hepatitis B surface antigen) in two (4%). In
      multivariate analysis, determining factors of cirrhosis at histologic examination
      were age and the antecedent of transfusion before 1993. Anti-HCV levels
      correlated with the elapsed time from transfusion to diagnosis, but not with age.
      CONCLUSION: An obstetric/gynecologic indication was the most frequent reason for
      both surgery and transfusion. Hepatitis B coinfection had a low prevalence and
      did not influence the severity of the liver disease, as age and the antecedent of
      transfusion certainly did. Infection length influenced the levels of anti-HCV
      antibodies in transfusion-associated hepatitis C.

PMID- 16884947
TI  - The polymorphisms of GSTM1, GSTT1, HYL1*2, and XRCC1, and aflatoxin B1-related
      hepatocellular carcinoma in Guangxi population, China.
AB  - AIM: High incidence rates of hepatocellular carcinoma (HCC) in Guangxi, China,
      are primarily due to heavy aflatoxin B1 (AFB1) exposure via corn and groundnut
      consumption. This study was designed to examine the polymorphisms associated of
      three carcinogen-metabolizing genes (namely: GSTM1, GSTT1, and HYL1*2) and one
      DNA-repair gene (namely: XRCC1), and investigate their role as susceptibility
      markers for HCC. METHODS: We conducted a case-control study including 257 cases
      of cancer and 649 hospital-based age, sex, ethnicity, and hepatitis B virus
      infection-matched controls to examine the role of genetic polymorphisms of four
      genes (GSTM1, GSTT1, HYL1*2, and XRCC1) in the context of HCC risk for the
      Guangxi population. Genomic DNA isolated from 2ml whole blood was used to
      genotype GSTM1, GSTT1, HYL1*2, and XRCC1 by means of polymerase chain reaction
      (PCR) and restriction fragment length polymorphism (RFLP) analysis. RESULTS:
      GSTT1-null genotype was not significantly associated with the risk of HCC, but
      GSTM1-null genotype [adjusted odds ratio (OR)=2.29, 95% confidence interval
      (CI)=1.59-3.31], HYL1*2 genotypes with 113 His allele (namely: YH/HH, adjusted
      OR=2.55, CI=1.78-3.65), and XRCC1 genotypes with 399 Gln allele (namely: AG/GG,
      adjusted OR=2.47, CI=1.72-3.54) increased the HCC risk. Compared with those
      individuals who did not express any putative risk genotypes as reference (OR=1),
      individuals featuring all of the putative risk genotypes [GSTM1-null, HYL1*2
      YH/HH, and XRCC1-AG/GG] did experience a significantly greater cancer risk
      (adjusted OR=10.83, CI=5.44-21.59, P(interaction)<0.01). Additionally, the risk
      of HCC did appear to differ more significantly among individuals featuring risk
      genotypes and high-level or long-term AFB1 exposure, whose adjusted ORs (CIs)
      were 52.44 (17.51-157.08) and 326.93 (38.58-2770.52), respectively. CONCLUSIONS:
      The results suggest that carcinogen metabolism and DNA-repair pathways may
      simultaneously modulate the risk of HCC for Guangxi population, and, particularly
      for these having high-level or long-term AFB1 exposure.

PMID- 16884948
TI  - Occult lymphadenopathic Kaposi's sarcoma associated with severe pulmonary
      hypertension: A clinical hint about the potential role of HHV-8 in HIV-related
      pulmonary hypertension?
AB  - Severe pulmonary hypertension (PH) mimicking idiopathic PH is an increasingly
      recognized complication of human immunodeficiency virus (HIV) infection. PH
      shares several histopathologic features with Kaposi's sarcoma (KS), the most
      common malignancy in AIDS patients, and molecular evidence of the vasculotropic
      Kaposi's sarcoma-associated herpesvirus or human herpesvirus 8 (HHV-8) has been
      found in the lung tissue of patients with the disease. Although the prevalence of
      HHV-8 infection is increased among HIV-infected patients, no clinical association
      between KS and PH has ever been reported. Herein, we described a 30-year-old HIV
      infected female co-infected with HHV-8 who developed severe PH coincident with
      occult KS. The clinical presentation of KS was unusual and remained masqueraded
      for years as an indolent cervical lymphadenopathy, without the typical cutaneous
      lesions. This is the first ever-reported case of PH associated with KS. Although
      the co-occurrence of both diseases in this patient could have been just a
      coincidence, the observation may also indicate that a relationship between HHV-8
      infection and HIV-associated PH exists. Coinfection with HHV-8 and occult
      lymphadenopatic KS should be considered in HIV-infected patients developing PH.

PMID- 16884949
TI  - hCMV induced IL-6 release in trophoblast and trophoblast like cells.
AB  - BACKGROUND: Human cytomegalovirus (hCMV) infection of the trophoblasts is a
      crucial event in virus transmission from mother to child, being one responsible
      factor for intrauterine infection of the unborn. Differences of virus replication
      in trophoblasts depending on time point of pregnancy and degree of
      differentiation of trophoblasts might influence this transmission. Furthermore,
      immunological reactions of the trophoblasts to hCMV infection might be important
      defence mechanisms too. OBJECTIVES: hCMV replication and interleukin-6 release in
      trophoblasts and trophoblast like cells (choriocarcinoma cells) was investigated.
      STUDY DESIGN: Trophoblasts from term and 1st trimester placentas were isolated
      and infected with hCMV. hCMV production and release to the supernatant as well as
      interleukin-6 release and interleukin-6 mRNA production by these infected cells
      was measured. Choriocarcinoma cell lines (JEG-3, JAR) were treated the same. Non
      infected trophoblasts were used as controls. RESULTS: In 1st trimester
      trophoblast, term trophoblasts and JEG-3 permissive hCMV replication was
      observed, although with different kinetics and efficiency. In JAR no complete
      virus replication was seen. High levels of interleukin-6 were measured in the
      supernatants of all hCMV infected cells immediately after infection. IL-6 mRNA
      upregulation was seen 48 h after infection in those cell types replication of
      hCMV occurred (1st trimester trophoblasts, term trophoblasts, JEG-3). At that
      time-point hCMV immediate early proteins appeared. In JARs no virus production
      and no IL-6 mRNA upregulation was seen, and IL-6 levels in the supernatant of
      these hCMV infected cells declined significantly until day 6 after infection
      compared to mock infected cells. CONCLUSION: These observations show that hCMV
      replication is influenced by the degree of trophoblast differentiation.
      Interleukin-6 is upregulated by hCMV infection, but is independent of complete
      virus replication.

PMID- 16884950
TI  - Comparison of multiple shell vial cell lines for isolation of enteroviruses: a
      national perspective.
AB  - BACKGROUND: Isolation of enterovirus in cell culture is still utilized by
      clinical laboratories, for vaccine research, and for identifying serotypes for
      disease surveillance. Use of a combination of cell lines is recommended yet this
      practice has not been rigorously examined for shell vials. OBJECTIVES: To
      evaluate the growth predilection of enterovirus serotypes for certain shell vial
      cell lines in clinical samples received at a national reference laboratory. STUDY
      DESIGN: We retrospectively reviewed results of samples submitted for viral
      culture over a 3-year period. PMK, BGM, RD, A549, and MRC-5 cell lines grown in
      shell vials were inoculated and serotyped. RESULTS: Of 55,816 cultures, 1047
      (1.9%) yielded enterovirus representing 18 serotypes. Echovirus 7, echovirus 9,
      and echovirus 30 were the most common serotypes recovered in 2002, 2003, and
      2004, respectively. PMK and MRC-5 recovered the majority of enterovirus isolates;
      the addition of BGM and RD cells increased our recovery rate by 13%. For 52.6% of
      enteroviral isolates, cytopathic effect was found in only a single cell line. PMK
      and BGM cells were effective in isolating coxsackieviruses, and RD and MRC-5 were
      useful particularly in isolating echoviruses. CONCLUSIONS: A combination of shell
      vial cell lines is still recommended for recovery of enteroviruses.

PMID- 16884951
TI  - The prevalence and significance of PDZ domain-phosphoinositide interactions.
AB  - PDZ domains predominate in multi-cellular organisms. They are ubiquitous protein
      interaction modules recognizing short peptide sequences generally situated at the
      C-terminal end of plasma membrane proteins. They contribute to the formation and
      spatial confinement of protein complexes and thereby play an essential role in
      the control of cell signaling. Recent studies indicate that PDZ domains can also
      interact with phosphoinositides (PIPs), signaling lipids with key-roles in
      receptor signal transduction, membrane trafficking, cytoskeleton remodeling and
      nuclear processes. In particular the PDZ domains of syntenin-1 and syntenin-2
      bind to phosphatidylinositol 4, 5-bisphosphate (PIP2) with high-affinity.
      Syntenin-1/PIP2 interaction is important for receptor cargo recycling and
      syntenin-2 plays a role in the organization of nuclear PIP2. In addition, other
      lower-affinity PDZ domain/PIPs interactions are documented. Here, we summarize
      and discuss the present knowledge about the occurrence, the biochemistry and the
      biology of PDZ domain-lipid interactions.

PMID- 16884952
TI  - Role of the calcarine cortex (V1) in perception of visual cues for saccades.
AB  - OBJECTIVE: To determine the initial level at which the pathways for cue
      perception, saccades and antisaccades diverge. METHODS: Two procedures: single
      pulse transcranial magnetic stimulation (sTMS) over posterior occiput and
      backward masking were used. A visual cue directed saccades to the left or right,
      either a pro-saccade (to the side of the cue but beyond it) or an antisaccade,
      i.e., contraversive saccade. No visual target was presented. RESULTS: Latencies
      of the two types of saccades did not differ. Focal sTMS applied unilaterally over
      V1 suppressed both perception of a cue flashed 80-90ms earlier contralaterally
      (but not ipsilaterally) and the appropriate saccade. Masking at a delay of 100ms
      abolished the appropriate saccade and cue perception. CONCLUSIONS: V1 is
      essential for the perception of a flashed cue and for executing appropriate pro-
      and contraversive saccades. Masking may occur beyond V1, where the pathways for
      perception and for saccades at least to the next visual processing level start
      separating. SIGNIFICANCE: VI is needed for rapid, accurate perceptual and motor
      responses to the crudest (left versus right) cues. It is unlikely that the
      "where" system can have a major direct input bypassing V1.

PMID- 16884953
TI  - Neurophysiologic assessment of mucopolysaccharidosis III.
AB  - OBJECTIVE: To describe finding of various neurophysiologic tests in patients with
      mucopolysaccharidosis III (MPS III) early in the disease course. METHODS:
      Patients were evaluated with flash visual evoked potentials (VEP), brainstem
      auditory evoked potentials (BAEP), electroencephalography (EEG), and nerve
      conduction studies (NCS) before they underwent hematopoietic stem cell
      transplantation (HSCT). RESULTS: Thirteen children underwent at least one
      neurophysiologic test before HSCT. The mean age at testing was 2.7 years. Ten of
      11 (91%) patients had a normal flash VEP, and all 9 who had BAEP had normal
      central conduction. EEG was normal in 7/13 (54%), with the others showing diffuse
      slowing. NCS was normal in 10/11 (91%) patients. CONCLUSIONS: Despite extensive
      central nervous system involvement in MPS III, flash VEP and BAEP are almost
      always normal. EEG is often abnormal early in the disease. SIGNIFICANCE: This is
      the first report of neurophysiologic tests in a large series of MPS III patients.

PMID- 16884954
TI  - Sleep disturbances independently predict heart failure in overweight middle-aged
      men.
AB  - BACKGROUND: Sleep disturbances are associated with manifest heart failure (HF).
      However, the relationship between sleep disturbances and incident HF has been
      less studied. AIMS: To investigate self-reported sleep disturbances as predictors
      of HF in a longitudinal, community-based cohort of 2314 middle-aged men. METHODS
      AND RESULTS: Data on self-reported sleep disturbances, as well as established
      risk factors for HF were collected and analyzed using Cox proportional hazards
      analyses. In multivariable Cox proportional hazards models adjusted for
      established risk factors for HF, the presence at baseline of sleep disturbances
      (hazard ratio [HR], 1.52; 95% confidence interval [CI], 1.16-1.99; p=0.002) was
      an independent risk factor for HF. There was evidence of effect modification
      between BMI and sleep disturbances. In multivariable-adjusted models, sleep
      disturbance (HR, 1.58; 95% CI, 1.13-2.21; p=0.008) was an independent risk factor
      for HF in overweight participants (BMI>25), but not in normal-weight participants
      (BMI< or =25). All results remained similar in a sub-sample excluding all
      participants suffering from a myocardial infarction during follow-up.
      CONCLUSIONS: Self-reported sleep disturbances imply an increased risk of
      subsequent HF in overweight middle-aged men, via mechanisms largely independent
      of established risk factors for HF, including an interim myocardial infarction.

PMID- 16884955
TI  - Systolic and diastolic heart failure: different phenotypes of the same disease?
AB  - Traditional pathophysiological concepts of chronic heart failure have largely
      focused on the haemodynamic consequences of ventricular systolic dysfunction. How
      these concepts relate to the pathophysiology of diastolic heart failure, i.e.,
      heart failure with a preserved ejection fraction is, however, unclear, causing
      uncertainty about pathophysiology, diagnosis and management. Recent measurements
      of regional myocardial systolic function in patients with diastolic heart failure
      indicate that systolic and diastolic heart failure may be more closely related
      than previously anticipated. Rather than being considered as separate diseases
      with a distinct pathophysiology, systolic and diastolic heart failure may be
      merely different clinical presentations within a phenotypic spectrum of one and
      the same disease. In this review, we will interpret these new insights in a
      broader conceptual context of chronic heart failure and design novel paradigms in
      which systolic and diastolic heart failure jointly progress in a
      pathophysiological time trajectory of only one disease.

PMID- 16884956
TI  - Re: A pilot randomised controlled trial of eccentric exercise to prevent
      hamstring injuries in community-level Australian Football.

PMID- 16884957
TI  - Lessons learned from Action Schools! BC--an 'active school' model to promote
      physical activity in elementary schools.
AB  - The 'active school' model offers promise for promoting school-based physical
      activity (PA); however, few intervention trials have evaluated its effectiveness.
      Thus, our purpose was to: (1) describe Action Schools! BC (AS! BC) and its
      implementation (fidelity and feasibility) and (2) evaluate the impact of AS! BC
      on school provision of PA. Ten elementary schools were randomly assigned to one
      of the three conditions: Usual Practice (UP, three schools), Liaison (LS, four
      schools) or Champion (CS, three schools). Teachers in LS and CS schools received
      AS! BC training and resources but differed on the level of facilitation provided.
      UP schools continued with regular PA. Delivery of PA during the 11-month
      intervention was assessed with weekly Activity Logs and intervention fidelity and
      feasibility were assessed using Action Plans, workshop evaluations, teacher
      surveys and focus groups with administrators, teachers, parents and students.
      Physical activity delivered was significantly greater in LS (+67.4 min/week; 95%
      CI: 18.7-116.1) and CS (+55.2 min/week; 95% CI: 26.4-83.9) schools than UP
      schools. Analysis of Action Plans and Activity Logs showed fidelity to the model
      and moderate levels of compliance (75%). Teachers were highly satisfied with
      training and support. Benefits of AS! BC included positive changes in the
      children and school climate, including provision of resources, improved
      communication and program flexibility. These results support the use of the
      'active school' model to positively alter the school environment. The AS! BC
      model was effective, providing more opportunities for "more children to be more
      active more often" and as such has the potential to provide health benefits to
      elementary school children.

PMID- 16884958
TI  - Pain characteristics in patients with unexplained chest pain and patients with
      ischemic heart disease.
AB  - BACKGROUND: Little scientific attention has been paid to providing a
      comprehensive multidimensional description of chest pain in patients with
      unexplained chest pain. AIMS: The aims of the present study were: (1) to describe
      the symptom chest pain, including the dimensions of intensity, quality, duration
      and location in patients with unexplained chest pain (UCP); and (2) to identify
      similarities and differences in how patients with UCP and patients with ischemic
      heart disease (IHD) describe chest pain. METHOD: A descriptive, correlational and
      comparative design. Totally 208 consecutive UCP patients and 40 IHD patients
      below 70 years of age participated. Pain was assessed using the instrument Pain-O
      Meter. RESULTS: The occurrence of chest pain was 79% (n=165) in UCP patients
      versus 60% (n=22) in the IHD patients (p=0.001). Patients with UCP reported
      greater pain intensity and used more sensory and affective words than IHD
      patients (p<0.01). Relationships between pain location and amount of body surface
      involved in the pain and pain intensity in both groups were found (p<0.001).
      CONCLUSIONS: Our results showed some defining characteristics of the UCP group,
      but the many similarities between the two groups in their experience of chest
      pain made it impossible to clearly differentiate the groups' pain profiles.

PMID- 16884959
TI  - Knowledge of management of epilepsy in young adults in Jordan.
AB  - PURPOSE: Nationwide studies on public knowledge of epilepsy have been undertaken
      in several countries, but not in Jordan. The purpose of this study was to
      evaluate knowledge of the management of epilepsy in Jordan. METHODS: A cross
      sectional study was performed during the period February-June 2005 on 16,044
      individuals selected randomly to represent all regions of Jordan. Respondents
      were interviewed and asked to complete a five-item questionnaire testing their
      knowledge of the management of epilepsy. RESULTS: Most of the individuals (77.9%)
      agreed that patients with epilepsy are best treated in a specialized hospital for
      neurological diseases. Although the largest percentage of the sample (86.7%)
      agreed that the best person to treat epilepsy is a neurologist, others believed
      that a hypnotherapist (25.4%) or a religious healer (22.6%) is. As an immediate
      measure during an attack of epilepsy, most respondents (82.6%) agreed that
      protecting the patient's head is most important. During the postseizure period,
      45.8% of respondents believed that offering the patient water or a cold or hot
      drink is appropriate. Two-thirds of the respondents (66.2%) agreed that epilepsy
      can be treated with drugs. Responses of the participants to the five items
      significantly differed with respect to age, gender, level of education, and
      occupation. CONCLUSION: Jordanians are reasonably well informed about most
      aspects of the management of epilepsy, but there is still a need for public
      education about this disorder.

PMID- 16884960
TI  - Right parietal activation during delusional state in episodic interictal
      psychosis of epilepsy: a report of two cases.
AB  - Magnetoencephalography (MEG) was used to image brain activity associated with
      delusions in episodic interictal psychosis of epilepsy. Two female patients aged
      65 and 68 with temporal lobe epilepsy were studied during and after a delusional
      state. Topographic images of the excess kurtosis (g2), the statistical index of
      spikelike activity, were obtained from unaveraged MEG recordings using an
      analysis called "synthetic aperture magnetometry" (SAM). For both patients, MEG
      waveforms and excess kurtosis images revealed spiky activity in the right
      inferior parietal region during the delusional state. A second MEG measurement
      after delusions were resolved with antipsychotic therapy revealed no excess
      kurtosis in the right parietal area. Likewise, the sharp waves on MEG recordings
      disappeared as well. Our results suggest association of the right inferior
      parietal cortex, including the supramarginal gyrus, with the delusional state of
      episodic interictal psychosis of epilepsy.

PMID- 16884961
TI  - Computational analyses show A-to-G mutations correlate with nascent mRNA hairpins
      at somatic hypermutation hotspots.
AB  - Activation-induced cytidine deaminase (AID) initiates Phase I somatic
      hypermutation (SHM) of antibody genes by deaminating deoxy-cytosine to deoxy
      uracil (C-to-U). These lesions trigger Phase II, a poorly understood process of
      error-prone repair targeting A-T pairs by DNA polymerase eta (Pol eta). Since Pol
      eta is also a reverse transcriptase, Phase II could involve copying off RNA as
      well as DNA templates. We explore this idea further since in an RNA-based pathway
      it is conceivable that adenosine-to-inosine (A-to-I) RNA editing causes A-to-G
      transitions since I like G pairs with C. Adenosine deaminases (ADARs) are known
      to preferentially edit A nucleotides that are preceded by an A or U (W) in double
      stranded RNA substrates. On this assumption and using a theoretical
      bioinformatics approach we show that a significant and specific correlation
      (P<0.002) exists between the frequency of WA-to-WG mutations and the number of
      mRNA hairpins that could potentially form at the mutation site. This implies
      roles for both RNA editing and reverse transcription during SHM in vivo and
      suggests definitive genetic experiments targeting the appropriate ADAR1 isoform
      (gammaINF-ADAR1) and/or Ig pre-mRNA templates.

PMID- 16884962
TI  - Optimal diving behaviour and respiratory gas exchange in birds.
AB  - This review discusses the advancements in our understanding of the physiology and
      behaviour of avian diving that have been underpinned by optimal foraging theory
      and the testing of optimal models. To maximise their foraging efficiency during
      foraging periods, diving birds must balance numerous factors that are directly or
      indirectly related to the replenishment of the oxygen stores and the removal of
      excess carbon dioxide. These include (1) the time spent underwater (which
      diminishes the oxygen supply, increases carbon dioxide levels and may even
      include a build up of lactate due to anaerobic metabolism), (2) the time spent at
      the surface recovering from the previous dive and preparing for the next
      (including reloading their oxygen supply, decreasing their carbon dioxide levels
      and possibly also metabolising lactate) and (3) the trade-off between maximising
      oxygen reserves for consumption underwater by taking in more air to the
      respiratory system, and minimising the energy costs of positive buoyancy caused
      by this air, to maximise the time available underwater to forage. Due to its
      importance in avian diving, replenishment of the oxygen stores has become
      integral to models of optimal diving, which predict the time budgeting of animals
      foraging underwater. While many of these models have been examined qualitatively,
      such tests of predictive trends appear fallible and only quantifiable support
      affords strong evidence of their predictive value. This review describes how the
      quantification of certain optimal diving models, using tufted ducks, indeed
      demonstrates some predictive success. This suggests that replenishment of the
      oxygen stores and removal of excess carbon dioxide have significant influences on
      the duration of the surface period between dives. Nevertheless, present models
      are too simplistic to be robust predictors of diving behaviour for individual
      animals and it is proposed that they require refinement through the incorporation
      of other variables that also influence diving behaviour such as, perhaps, prey
      density and predator avoidance.

PMID- 16884963
TI  - Silica-immobilized enzyme reactors; application to cholinesterase-inhibition
      studies.
AB  - A rapid and economical method is reported for the preparation of an immobilized
      enzyme reactor (IMER) using silica-encapsulated equine butyrylcholinesterase
      (BuChE) as a model system. Peptide-mediated silica formation was used to
      encapsulate BuChE, directly immobilizing the enzyme within a commercial pre
      packed column. The silica/enzyme nanocomposites form and attach simultaneously to
      the metal affinity column via a histidine-tag on the silica-precipitating
      peptide. BuChE-IMER columns were integrated to a liquid chromatography system and
      used as a rapid and reproducible screening method for determining the potency of
      cholinesterase inhibitors. The IMER preparation method reported herein produces
      an inert silica-encapsulation matrix with advantages over alternative systems,
      including ease of preparation, high immobilization efficiency (70-100%) and
      complete retention of activity during continuous use.

PMID- 16884964
TI  - Extrahepatic manifestations of Hepatitis C Virus infection: a general overview
      and guidelines for a clinical approach.
AB  - Hepatitis C Virus is associated with a wide series of extrahepatic
      manifestations. Based on available data the link between the virus and some of
      these extrahepatic diseases is only suggested and needs further confirmation.
      Hepatitis C Virus-related lymphoproliferative disorders, whose prototype is mixed
      cryoglobulinaemia, represent the most closely related extrahepatic manifestations
      of Hepatitis C Virus. Other Hepatitis C Virus-associated disorders include
      nephropathies, thyreopathies, sicca syndrome, idiopathic pulmonary fibrosis,
      porphyria cutanea tarda, lichen planus, diabetes, chronic polyarthritis,
      cardiopathy and atherosclerosis. A pathogenetic link between Hepatitis C Virus
      and some extrahepatic manifestations was confirmed by their responsiveness to
      antiviral therapy, which is now deemed the first therapeutic option to consider.
      By contrast, there are diseases where treatment with interferon was ineffective
      or dangerous. The aim of the present paper is to outline the most recent evidence
      concerning extrahepatic disorders that are possibly associated with Hepatitis C
      Virus infection. Special emphasis will be given to discussion of the most
      appropriate clinical approaches to be adopted in order to diagnose, treat
      (possibly prevent) and follow-up extrahepathic diseases in patients with
      Hepatitis C Virus infection.

PMID- 16884965
TI  - Prolonged Hepatitis B surface antigen positivity in Hepatitis B vaccine
      recipients.

PMID- 16884966
TI  - Sol-gel derived aluminosilicate coatings on alumina as substrate for osteoblasts.
AB  - Rat bone marrow stromal cell differentiation on aluminosilicate 3Al(2)O(3)
      2SiO(2) coatings was investigated. Thin ceramic coatings were prepared on alpha
      alumina substrates by the sol-gel process and calcined in order to establish an
      amorphous aluminosilicate ceramic phase with and without nanosized transitional
      mullite crystals. In addition, coatings of thermally sprayed aluminosilicate and
      diphasic gamma-alumina-silica nanosized colloids were prepared. Cell culture
      testing by rat osteoblasts showed good biocompatibility for aluminosilicates with
      sustained normal osteoblast functions. Despite mutual disparities in physical and
      chemical nanostructures, the culture findings suggested fairly similar osteoblast
      response to all tested coatings. The results suggest that topographical frequency
      parameters and chemical uniformity are important parameters in determining the
      best conditions for osteoblasts on sol-gel derived aluminosilicate materials.

PMID- 16884967
TI  - Influence of alloying elements on the corrosion stability of CoCrMo implant alloy
      in Hank's solution.
AB  - The behavior of a CoCrMo alloy and its components was studied in simulated
      physiological solution (Hank's solution) using cyclic voltammetry (CV) and
      electrochemical impedance spectroscopy (EIS). The passivation of all samples
      occurred spontaneously at the open circuit potential. The composition of the
      oxide films as a function of the solution components and the applied potential is
      discussed. The electrochemical properties of the spontaneously passivated
      electrodes at the open circuit potential were studied by EIS. The polarization
      resistance (R(p)) and the electrode capacitance (C(dl)) were determined. The
      higher R(p) of the alloy than of the chromium pointed to the stabilizing effect
      of the other alloy components. The concentration of the metallic ions in a
      simulated physiological solution, measured by inductively coupled plasma-mass
      spectrometry, was in accordance with the values of both the R(p) determined from
      EIS data and current densities measured with CV.

PMID- 16884968
TI  - Response rate of bone mineral density to teriparatide in postmenopausal women
      with osteoporosis.
AB  - PURPOSE: It is desirable for clinicians to know what bone mineral density (BMD)
      response they can expect in women treated with osteoporosis therapies. The focus
      of this analysis was to determine what percentage of women attained a lumbar
      spine BMD response to teriparatide that equaled or exceeded the least significant
      change (LSC) value of 3%. METHODS: Data from three clinical trials involving
      postmenopausal women with osteoporosis were examined. The Fracture Prevention
      Trial was a double-blinded, placebo-controlled clinical trial examining the
      safety and efficacy of teriparatide 20 and 40 microg/day. The other two trials
      were double-blinded, head-to-head comparisons of alendronate 10 mg/day and
      teriparatide 20 or 40 microg/day, respectively. Only treatment-compliant women
      who had lumbar spine BMD measurements at all specified time points in these
      trials were included. For reference, we also examined the percentage of women
      with lumbar spine BMD responses to alendronate. Hip BMD responses that equaled or
      exceeded 3% were also examined. RESULTS: According to the LSC criteria, 91% of
      the teriparatide 20 microg/day group and 94% of the teriparatide 40 microg/day
      group were lumbar spine BMD responders at 18 months in the Fracture Prevention
      Trial. In the teriparatide 20 microg/alendronate head-to-head trial, 94% of women
      receiving teriparatide had a lumbar spine BMD response that equaled or exceeded
      the 3% criterion at 18 months compared to 75% of those receiving alendronate 10
      mg/day (p < 0.01). In the teriparatide 40 microg/day group of the other head-to
      head trial, 92% of women achieved the 3% criterion for the lumbar spine at 12
      months compared to 69% of those receiving alendronate 10 mg/day (p < 0.01). The
      median 3-month change in amino-terminal extension peptide of procollagen type 1
      [PINP] in women who had a lumbar spine BMD response to teriparatide at 18 months
      was larger than in women who did not have a lumbar spine BMD response. However,
      the median 3-month PINP change in lumbar spine BMD nonresponders still exceeded
      the LSC value of 10 microg/L. Although the percentage of teriparatide-treated
      women with a hip BMD response that met the 3% criterion was significantly greater
      than for placebo, there was no significant difference between the percentage of
      teriparatide 20 microg/day and alendronate 10 mg/day responders in the comparison
      trial. The baseline characteristics of teriparatide lumbar spine responders and
      nonresponders were similar. CONCLUSION: This analysis demonstrates that the vast
      majority of treatment-compliant postmenopausal women with osteoporosis and
      minimal prior bisphosphonate exposure have a lumbar spine BMD response to
      teriparatide that meets or exceeds the LSC. The characteristics of teriparatide
      responders and nonresponders were not significantly different; thus, we were
      unable to discern any characteristics that could be used to identify potential
      nonresponders.

PMID- 16884970
TI  - Tumor necrosis factor antagonists: different kinetics and/or mechanisms of action
      may explain differences in the risk for developing granulomatous infection.
AB  - OBJECTIVE: Tumor necrosis factor (TNF) antagonists fall into 2 classes:etanercept
      (ETA) is a soluble TNF receptor, while infliximab (INF) and adalimumab (ADA) are
      monoclonal antibodies against TNF. All 3 drugs are effective in treating
      rheumatoid arthritis. However, these agents have been associated with an
      increased risk of granulomatous infections, such as tuberculosis and
      histoplasmosis. Several reports indicate that the incidence of granulomatous
      infections may potentially be higher in individuals treated with INF than ETA.
      METHODS: We conducted a comprehensive literature search (1966 to 2004) to review
      the role of TNF in normal and disease states, and the mechanisms of action of the
      TNF inhibitors. Specifically, we searched for possible mechanisms for the
      apparent increase in granulomatous infections associated with TNF inhibitors and
      for reasons that there may be differences between them. RESULTS: Infection may
      result from a number of differences between ETA and INF or ADA. First, binding
      avidities are different, with ETA binding in a 1:1 ratio and INF/ADA binding in 2
      to 3:1 ratios. Second, the clearances of ADA, ETA, and INF are different, being
      about 13 times higher for ETA than INF or ADA, thus resulting in higher steady
      state drug levels for ADA and INF. Also, the methods of administration are
      different, intravenously (for INF) versus subcutaneously (for ETA and ADA), which
      results in lower peak concentrations for ETA and ADA, potentially explaining some
      of the differences in effects on granuloma formation. Third, INF and ADA have
      somewhat different mechanisms of action from ETA: INF and ADA are associated with
      antibody-mediated cell lysis, while ETA is not; INF may induce apoptosis in some
      tissues (eg, gastrointestinal [GI] mucosa) while ETA does not--although this is
      controversial and may not be true at steady state in synovium, where both drugs
      seem to cause apoptosis; ETA binds lymphotoxin-alpha while INF does not (ETA may
      thus be more efficient at preventing granuloma formation by this mechanism than
      INF); finally, ADA and INF seem to inhibit IFN-gamma expression (probably
      indirectly), while ETA does not. CONCLUSIONS: There are significant differences
      between the 2 classes of TNF antagonists in terms of both their kinetics and
      mechanisms of action. These differences may help explain the apparent differences
      in the incidence of granuloma-dependent infections among them.

PMID- 16884969
TI  - Serotonin transporter and receptor expression in osteocytic MLO-Y4 cells.
AB  - Neurotransmitter regulation of bone metabolism has been a subject of increasing
      interest and investigation. We reported previously that osteoblastic cells
      express a functional serotonin (5-HT) signal transduction system, with mechanisms
      for responding to and regulating uptake of 5-HT. The clonal murine osteocytic
      cell line, MLO-Y4, demonstrates expression of the serotonin transporter (5-HTT),
      and the 5-HT1A, and 5-HT2A receptors by real-time RT-PCR and immunoblot analysis.
      Immunohistochemistry using antibodies for the 5-HTT, and the 5-HT1A and 5-HT2A
      receptors reveals expression of all three proteins in both osteoblasts and
      osteocytes in rat tibia. 5-HTT binding sites were demonstrated in the MLO-Y4
      cells with nanomolar affinity for the stable cocaine analog [125I]RTI-55.
      Imipramine and fluoxetine, antagonists with specificity for 5-HTT, show the
      highest potency to antagonize [125I]RTI-55 binding in the MLO-Y4 cells. GBR
      12935, a relatively selective dopamine transporter antagonist, had a much lower
      potency, as did desipramine, a selective norepinephrine transporter antagonist.
      The maximal [3H]5-HT uptake rate in MLO-Y4 cells was 2.85 pmol/15 min/well, with
      a Km value of 290 nM. Imipramine and fluoxetine inhibited specific [3H]5-HT
      uptake with IC50 values in the nanomolar range. 5-HT rapidly stimulated PGE2
      release from MLO-Y4 cells; the EC50 for 5-HT was 0.1 microM, with a 3-fold
      increase seen at 60 min. The rate-limiting enzyme for serotonin synthesis,
      tryptophan hydroxylase, is expressed in MLO-Y4 cells as well as osteoblastic
      MC3T3-E1 cells. Thus, osteocytes, as well as osteoblasts, are capable of 5-HT
      synthesis, and express functional receptor and transporter components of the 5-HT
      signal transduction system.

PMID- 16884971
TI  - Therapeutic options for resistant lupus nephritis.
AB  - OBJECTIVES: To summarize the therapeutic options for proliferative and membranous
      lupus nephritis that is resistant to conventional treatment. METHODS: Treatment
      trials in human lupus nephritis from years 1985 to 2005 that have been published
      in the English literature were searched by Medline using the keywords "lupus,"
      "nephritis," "glomerulonephritis," "renal," "refractory," "resistant,"
      "recalcitrant," "cyclophosphamide," "mycophenolate," "cyclosporin," "tacrolimus,"
      "leflunomide," "intravenous immunoglobulin," "apheresis," "plasmapheresis,"
      "immunoadsorption," "marrow transplantation," "stem cell transplantation,"
      "immunoablative," "rituximab," and "biologics." Laboratory, histological, and
      nonrenal lupus studies were excluded. RESULTS: There is no universal definition
      of treatment resistance in lupus nephritis. Controlled trials in refractory lupus
      nephritis are largely unavailable. Open-labeled studies have reported success of
      newer immunosuppressive drugs, immunomodulatory therapies, and the biological
      agents such as mycophenolate mofetil (MMF), calcineurin inhibitors, leflunomide,
      intravenous immunoglobulin, immunoadsorption, and rituximab in the treatment of
      cyclophosphamide (CYC) resistant proliferative lupus nephritis. More aggressive
      CYC regimens have been used in lupus nephritis, but at the expense of more
      toxicities. For membranous lupus nephritis (MLN), a combination of
      corticosteroids with either azathioprine, chlorambucil, cyclosporin A, MMF, or
      CYC is initially effective in two-thirds of patients. More aggressive and costly
      regimens should be reserved for truly refractory disease with persistent
      nephrotic syndrome or declining renal function. Evidence regarding the efficacy
      of MMF in refractory MLN is conflicting and controlled trials are necessary to
      resolve the controversy. CONCLUSIONS: The treatment of refractory lupus nephritis
      remains anecdotal. An international consensus in the renal response criteria
      should be developed and validated so that controlled trials can be performed to
      compare the efficacy of various treatment modalities.

PMID- 16884972
TI  - The history of bacteriologic concepts of rheumatic fever and rheumatoid
      arthritis.
AB  - OBJECTIVES: Review of the development of etiologic and pathogenetic concepts of
      rheumatic fever (RF) and rheumatoid arthritis (RA) from the beginning of clinical
      bacteriology to the discovery of antibiotics. METHOD: Analysis of English and
      German language publications pertaining to bacteriology and "rheumatism" between
      the 1870s and 1940s. RESULTS: Early in the 20th century there was a widely held
      belief that a microbial cause would eventually be found for most diseases. This
      encouraged pursuit of the intermittent findings of positive blood and synovial
      fluid cultures in cases of RF and RA. Development of a streptococcal
      agglutination test supported the erroneous belief that RA is a streptococcal
      infection, while the simultaneous development of other immunologic tests for
      streptococci suggested that a hemolytic streptococcus was etiologic in RF. Table
      1 provides a chronology of major events supporting and retarding resolutions.
      CONCLUSIONS: Much of the conflicting data and inferences regarding the etiology
      of RF and RA can be attributed to the absence or inadequacy of controls in
      observations of clinical cohorts and laboratory experiments.

PMID- 16884973
TI  - Factors that affect the number of tender points in fibromyalgia and chronic
      widespread pain patients who did not meet the ACR 1990 criteria for fibromyalgia:
      are tender points a reflection of neuropathic pain?
AB  - OBJECTIVE: This study aims to compare fibromyalgia (FM) and chronic widespread
      pain (CWP) patients who do not fulfill the criteria for tender points (TP).
      METHODS: We included 150 patients diagnosed with FM according to ACR 1990
      criteria and 42 patients with CWP who did not fulfill TP criteria for FM into the
      study. The clinical features of the patients were recorded, and the TP count was
      determined. By means of a visual analog scale (VAS), all patients were questioned
      about the severity of pain and FM-related symptoms. In addition, the patients
      were administered the Duke Anxiety Depression (Duke-AD) scale and somatization
      symptom questionnaire. Leeds Assessment of Neuropathic Symptoms and Signs (LANSS)
      pain scale was used to determine the neuropathic pain score. RESULTS: According
      to VAS, the severity of pain, sleep disturbance, the number of somatization
      symptoms, LANSS, and Duke-AD scores were significantly higher in FM patients than
      in patients with CWP (all P values <0.05). The number of TP correlated with
      severity of pain (r = 0.32, P < 0.001), the number of somatization symptoms (r =
      0.26, P = 0.01), sleep disturbance (r = 0.18, P = 0.01), and LANSS score (r =
      0.4, P < 0.001). Multiple logistic regression analysis revealed that independent
      factors that affected the presence of > or =11 TP were the severity of pain on
      VAS (OR: 1.03, 95% CI: 1.01-1.06, P = 0.045) and LANSS score (OR: 1.36, 95% CI:
      1.12-1.62, P = 0.001). CONCLUSIONS: CWP patients have symptoms similar to FM
      patients, though less severe. The most important factor that affects the criteria
      for fulfilling the number TP in CWP patients is the neuropathic pain score, which
      suggests that FM is primarily a neuropathic pain syndrome.

PMID- 16884974
TI  - Spinal tuberculosis: a longitudinal study with clinical, laboratory, and imaging
      outcomes.
AB  - OBJECTIVES: To study imaging changes associated with spinal tuberculosis (ST)
      over time and evaluate their association with clinical and laboratory data.
      METHODS: Between 1997 and 2004, patients with proven ST in our institution were
      prospectively enrolled and treated for 1 year. Clinical and laboratory data were
      collected at baseline and every 3 months. Computed tomography (CT) and magnetic
      resonance imaging (MRI) were performed at baseline. MRI was performed at least
      twice during treatment and at the end of treatment. RESULTS: Nineteen patients
      were enrolled; neurological signs were present at baseline in 14 patients (74%).
      Initial MRI/CT findings comprised (in percentages of patients) the following:
      paravertebral abscesses (100/100); intradiscal abscesses (47/0); and epidural
      abscesses (82/24) with spinal cord compression (64/18) or radicular compression
      (36/0). Edema of the vertebral body was observed on initial MRI in all the
      patients. Full follow-up data were available for 15 patients: all were cured with
      a mean follow-up of 25 months after the end of treatment. Weight gain was nearly
      maximal at 6 months, and pain relief was achieved within 9 months. C-reactive
      protein returned to normal after 3 months. On MRI, all epidural abscesses
      disappeared within 9 months; paravertebral abscesses disappeared after 3, 6, and
      12 months in 45, 50, and 85% of patients, respectively. Vertebral body signal
      converted to a fatty signal in 75% of cases at 12 months. CONCLUSIONS:
      Significant imaging abnormalities can persist after successful treatment of ST.
      These findings suggest that MRI need not be repeated in patients with clinical
      and laboratory improvement.

PMID- 16884975
TI  - Anesthetic preconditioning: how important is it in today's cardiac anesthesia?

PMID- 16884976
TI  - Myocardial damage prevented by volatile anesthetics: a multicenter randomized
      controlled study.
AB  - OBJECTIVE: The purpose of this study was to evaluate the effects of volatile
      anesthesia versus total intravenous anesthesia on cardiac troponin release in off
      pump coronary artery bypass grafting (OPCAB). DESIGN: The authors performed a
      multicenter randomized controlled study to compare cardiac troponin release in
      patients receiving either volatile anesthetics or total intravenous anesthesia
      for cardiac surgery on the beating heart, which is an excellent model of human
      myocardial ischemia. SETTING: Three university hospitals. PARTICIPANTS: The
      authors randomly assigned 57 patients to desflurane (volatile anesthetic) and 55
      patients to propofol (intravenous anesthetic) in addition to an opiate-based
      anesthesia for OPCAB. INTERVENTIONS: The 2 groups of patients received either
      desflurane (volatile anesthetic) or propofol in addition to an opiate-based
      anesthesia for OPCAB. Peak postoperative troponin I release was measured as a
      marker of myocardial necrosis. Prolonged hospitalization was considered as a
      secondary outcome. MEASUREMENTS AND MAIN RESULTS: Patient mean age was 69 years,
      and 82% were men. There was a significant (p < 0.001) reduction in postoperative
      median (25th-75th percentiles) peak of troponin I in patients receiving volatile
      anesthetics, 1.2 (0.9-1.9) ng/dL, compared with patients receiving total
      intravenous anesthesia, 2.7 (2.1-4.0) ng/dL. This myocardial protection resulted
      in a reduced (p = 0.04) number (percentage) of patients requiring postoperative
      inotropes, 20 (35%) versus 31 (56%), and a reduced number (percentage) of
      patients submitted to prolonged hospitalization (> or =7 days), 7 (12%) versus 20
      (36%) in the 2 groups (p = 0.005). One patient receiving total intravenous
      anesthesia died within 30 days of surgery. CONCLUSIONS: Myocardial damage
      measured by cardiac troponin release could be reduced by volatile anesthetics
      during OPCAB. Because patients underwent cardiac surgery on the beating heart,
      these results could have implications for cardiac patients undergoing noncardiac
      surgery.

PMID- 16884977
TI  - Sevoflurane-remifentanil versus propofol-remifentanil anesthesia at a similar
      bispectral level for off-pump coronary artery surgery: no evidence of reduced
      myocardial ischemia.
AB  - OBJECTIVE: Sevoflurane could decrease myocardial ischemic injury in patients
      undergoing off-pump coronary artery bypass surgery. This study was designed to
      compare postoperative troponin I (cTnI) concentrations after sevoflurane
      remifentanil versus propofol-remifentanil anesthesia. DESIGN: Prospective,
      randomized single-blind clinical study. SETTING: University hospital.
      PARTICIPANTS: Eighteen patients. INTERVENTIONS: General anesthesia was conducted
      with sevoflurane-remifentanil (n = 9) or propofol-remifentanil (n = 9).
      Administration of sevoflurane and propofol was adjusted to maintain the
      bispectral index (BIS) between 40 and 60. MEASUREMENTS AND MAIN RESULTS: Groups
      were comparable regarding the patients' characteristics. The objective of BIS was
      maintained in both groups except during the period of coronary artery grafts (p <
      0.001) when the BIS number in the propofol group fell below 40 and was
      significantly lower than in the sevoflurane group. Intraoperative hemodynamic
      variables were similar between groups. No patient required cardiopulmonary
      bypass. Need for inotropic and vasoactive support during the first graft was not
      necessary in the propofol group and occurred in 4 patients in the sevoflurane
      group (not significant). During the second graft, 2 patients in the propofol
      group and 3 in the sevoflurane group needed hemodynamic support. Postoperative
      hemodynamic variables were comparable between groups. Areas under the curve of
      postoperative increases in cTnI were 27.0 +/- 38.6 and 17.4 +/- 14.6 ng/mL/hour
      in the sevoflurane and propofol groups, respectively (not significant).
      CONCLUSION: This study does not support cardioprotective effects of sevoflurane.
      The particularly short total cumulative duration of ischemia and the relatively
      low administered end-tidal sevoflurane concentrations may explain this result.

PMID- 16884978
TI  - Opioids and cardioprotection: the impact of morphine and fentanyl on recovery of
      ventricular function after cardiopulmonary bypass.
AB  - OBJECTIVES: Experimental studies have shown that opioids protect the myocardium
      from ischemic injury and that opioid cardioprotection is enhanced by the
      coadministration of volatile anesthetics. Previous data suggest that morphine
      produces a more potent cardioprotective effect than fentanyl. The present study
      investigated the effect of the choice of intraoperative opioid (morphine or
      fentanyl) on recovery of myocardial function after coronary artery bypass graft
      (CABG) surgery. DESIGN: Prospective, randomized study. SETTING: University
      hospital. PARTICIPANTS: Forty-six patients undergoing CABG surgery.
      INTERVENTIONS: Patients were randomly assigned to receive either morphine (40 mg)
      or fentanyl (1,000 mug) before cardiopulmonary bypass (CPB). Global cardiac
      function was assessed intraoperatively using the myocardial performance index
      (MPI), which combines echocardiographic parameters of both systolic and diastolic
      function. MEASUREMENTS AND MAIN RESULTS: The MPI (median [range]) was increased
      after CPB in the fentanyl group, indicating a significant worsening of global
      left ventricular function (0.43 [0.28-0.54] baseline; 0.49 [0.32-0.64] 15 minutes
      post-CPB; 0.51 [0.36-0.63] end of operation; p < 0.05 post-CPB compared with
      baseline). The MPI improved in the morphine group after CPB (0.44 [0.32-0.64]
      baseline; 0.36 [0.24-0.45] 15 minutes post-CPB; 0.34 [0.20-0.46] end of
      operation; p < 0.05 post-CPB compared with baseline and the fentanyl group).
      CONCLUSIONS: In patients undergoing CPB, global ventricular function is enhanced
      by the administration of morphine prior to the ischemic insult of cardioplegic
      arrest.

PMID- 16884979
TI  - Effects of sevoflurane on cytokine balance in patients undergoing coronary artery
      bypass graft surgery.
AB  - OBJECTIVE: The effects of sevoflurane on proinflammatory cytokines related to
      ischemic-reperfusion injury are not clear. The hypothesis was tested that
      sevoflurane decreases myocardial ischemic-reperfusion injury by suppressing
      proinflammatory cytokines. DESIGN: Prospective, randomized study. SETTING: A
      medical university heart center. PARTICIPANTS: Twenty-three patients undergoing
      coronary artery bypass surgery allocated randomly into 2 groups. INTERVENTIONS:
      Anesthesia for 23 patients undergoing coronary artery bypass surgery was
      maintained using either fentanyl (30 microg/kg) with propofol (2-8 mg/kg/h) in
      the control group (n = 10) or fentanyl (30 microg/kg) with 0.5% to 1.0%
      sevoflurane in the sevoflurane group (n = 13). MEASUREMENTS AND MAIN RESULTS:
      Interleukin (IL)-6, IL-8, IL-10, and IL-1 receptor antagonist (IL-1ra) were
      measured by enzyme-linked immunosorbent assay. Troponin-T and creatine kinase-MB
      isoenzyme (CK-MB) were measured by enzyme immunoassay and ultraviolet absorption
      spectrophotometry, respectively. Serum IL-6 and IL-8 concentrations in both
      groups increased significantly over baseline from 60 minutes after declamping the
      aorta (p < 0.001). The increases were greater in the control group than in the
      sevoflurane group (p < 0.05). Serum IL-10 and IL-1ra concentrations in both
      groups increased significantly over baseline from 60 minutes after declamping the
      aorta (p < 0.001). There were no differences between the two groups. Serum
      troponin-T and CK-MB concentrations increased significantly in both groups from
      60 minutes after declamping the aorta (p < 0.001); the increases were greater in
      the control group (p < 0.05). CONCLUSION: Sevoflurane suppressed the production
      of IL-6 and IL-8, but not IL-10 and IL-1ra. Changes in the balance between pro-
      and anti-inflammatory cytokines may be one of the most important mechanisms of
      myocardial protection caused by sevoflurane.

PMID- 16884980
TI  - Effect of isoflurane on echocardiographic left-ventricular relaxation indices in
      patients with diastolic dysfunction due to concentric hypertrophy and ischemic
      heart disease.
AB  - OBJECTIVE: The purpose of this study was to investigate whether isoflurane, a
      known negative lusitropic agent, exacerbates diastolic dysfunction in patients
      with preexisting impaired relaxation. DESIGN: Prospective, experimental study.
      SETTING: Single-institution, university hospital. PARTICIPANTS: Twenty-five
      patients with diastolic dysfunction due to concentric hypertrophy and ischemic
      heart disease undergoing elective coronary artery bypass graft surgery.
      INTERVENTIONS: After approval of the local ethics committee and informed consent,
      patients randomly received sufentanil/midazolam anesthesia plus either 0.5 to 1.0
      minimum alveolar concentration of isoflurane (n = 15) or weight-adjusted boli of
      urapidil (n = 10) during preparation of the internal mammary artery. Changes in
      hemodynamic parameters and echocardiographic diastolic indices before and after
      drug administration were compared. Filling pressures during the study were kept
      constant within normal range. MEASUREMENTS AND MAIN RESULTS: Hemodynamic changes
      measured by invasive arterial and pulmonary arterial pressures were comparable
      between isoflurane and urapidil. Both interventions led to a marked reduction in
      afterload that was accompanied by a significant increase in thermodilution
      cardiac output and stroke volume. Transesophageal echocardiographic relaxation
      indices were also comparable between groups. Transmitral and tissue Doppler E
      waves increased significantly, leading to larger E/A and Em/Am ratios; whereas
      the deceleration time and the isovolumetric relaxation time decreased
      significantly. CONCLUSION: Isoflurane did not exacerbate diastolic dysfunction in
      patients with concentric hypertrophy and ischemic heart disease. In contrast,
      isoflurane led to a "normalization" of the relaxation pattern that was attributed
      to a reduction in left-ventricular loading conditions.

PMID- 16884981
TI  - Dexmedetomidine-ketamine and propofol-ketamine combinations for anesthesia in
      spontaneously breathing pediatric patients undergoing cardiac catheterization.
AB  - OBJECTIVE: The purpose of this study was to compare the effects of
      dexmedetomidine-ketamine and propofol-ketamine combinations on hemodynamics,
      sedation level, and the recovery period in pediatric patients undergoing cardiac
      catheterization. DESIGN: Prospective, randomized trial. SETTING: University
      hospital. PARTICIPANTS: Children (n = 44) undergoing cardiac catheterization.
      INTERVENTIONS: The dexmedetomidine plus ketamine group (group 1, n = 22) received
      an infusion over 10 minutes of 1 microg/kg of dexmedetomidine and ketamine, 1
      mg/kg, as a bolus, for induction. The patients then received an infusion of 0.7
      microg/kg/h of dexmedetomidine and 1 mg/kg/h of ketamine for maintenance. The
      propofol plus ketamine group (group 2, n = 22) received 1 mg/kg of propofol and 1
      mg/kg of ketamine for induction. The patients received 100 microg/kg/min of
      propofol and 1 mg/kg/h of ketamine by infusion for maintenance. Additional doses
      of ketamine, 1 mg/kg, were administered when a patient showed discomfort in both
      groups. MEASUREMENTS AND MAIN RESULTS: Hemodynamic data, respiratory rate,
      bispectral index, and sedation scores were recorded after induction and every 15
      minutes thereafter. The time to reach a Steward recovery score of 6 was recorded.
      The heart rate in group 1 was significantly lower (average 10-20 beats/min) than
      group 2 after induction and throughout the procedure. Ketamine consumption in
      group 1 was significantly more than in group 2 (2.03 mg/kg/h v 1.25 mg/kg/h) for
      maintenance (p < 0.01). The recovery time was also longer in group 1 than in
      group 2 (49.54 v 23.16 minutes, respectively; p < 0.01). CONCLUSIONS: The
      dexmedetomidine-ketamine combination was not superior to a propofol-ketamine
      combination because of insufficient sedation and analgesia and a longer recovery
      time.

PMID- 16884982
TI  - Anesthetic technique (sufentanil versus ketamine plus midazolam) and quantitative
      electroencephalographic changes after cardiac surgery.
AB  - OBJECTIVES: Cardiac surgery involving cardiopulmonary bypass is associated with
      neurologic deterioration. Several interventions, including anesthetic techniques,
      have been designed to limit ischemic brain damage and have been evaluated in
      animals. Markers of neurologic injury may facilitate the assessment of these
      interventions in humans. DESIGN: A blinded randomized prospective study comparing
      2 anesthetic techniques (one sufentanil-based, the other ketamine and midazolam
      based) in patients undergoing cardiac surgery. Quantitative
      electroencephalography was used to detect postoperative neurologic injury.
      SETTING: Major teaching hospital. PARTICIPANTS: Forty-two patients aged 18 to 70
      years undergoing cardiac surgery. INTERVENTIONS: Patients were anesthetized with
      either a sufentanil-based or a ketamine and midazolam-based technique for cardiac
      surgery with cardiopulmonary bypass. Quantitative electroencephalography was
      performed preoperatively as well as 5 to 6 days postoperatively. MEASUREMENTS AND
      MAIN RESULTS: Quantitative electroencephalography outcome did not differ (p >
      0.05) between the 2 groups. It showed significant deterioration between
      preoperative and postoperative assessments with a decrease in faster and an
      increase in slower frequencies. In addition, the alpha attenuation index
      decreased. This may reflect a decrease in alertness. Both the intergroup
      comparisons and the assessment of individual changes failed to reveal significant
      differences between the anesthetic techniques. The adjuvant use of isoflurane
      correlated with less deterioration of quantitative electroencephalographic
      variables. CONCLUSIONS: The use of either sufentanil-based or ketamine and
      midazolam-based anesthetic techniques for cardiac surgery with cardiopulmonary
      bypass had no effects on a marker of postoperative neurologic injury (ie,
      quantitative electroencephalography).

PMID- 16884983
TI  - Risk evaluation of cardiac surgery in octogenarians.
AB  - OBJECTIVE: To assess the predictive value of risk factors in the European System
      for Cardiac Operative Risk Evaluation (EuroSCORE) for cardiac surgery on
      octogenarians. DESIGN: An observational study of octogenarians undergoing cardiac
      surgery and average-aged controls matched according to the cardiac surgical
      procedure. SETTING: A university hospital. PARTICIPANTS: One hundred sixty-two
      consecutive patients 80 years or older who underwent cardiac surgery between
      January 1, 2001, and June 30, 2003, and 162 average-aged controls. INTERVENTIONS:
      None. MEASUREMENTS AND MAIN RESULTS: Risk factors according to the EuroSCORE (The
      European System for Cardiac Risk Evaluation) model and EuroScore algorithm
      without an age component (EuroSCOREex) were evaluated. The EuroSCORE model and
      EuroSCOREex predicted mortality (odds ratio 1.4) and morbidity (odds ratio 1.2
      and 1.3, respectively) equally well in both age groups. Adding age group
      information into the EuroSCOREex model in combined data, the odds ratio estimate
      was 3.5 for age group. The 30-day mortality of octogenarians was 8.6% versus 1.9%
      in controls (p < 0.01). Incidences of organ-related complications were
      comparable. Octogenarians spent more days in the hospital's intensive care unit
      and surgical ward than did controls (3.4 +/- 3.3 days v 2.7 +/- 3.1 days, p <
      0.01; 9.9 +/- 5.8 days v 8.6 +/- 3.8 days, p = 0.02). Only 31 (19.1%)
      octogenarians were discharged home, whereas the corresponding number was 66
      (40.7%) in controls (p < 0.01). CONCLUSIONS: Risk factors other than age were not
      higher in octogenarians, and the EuroSCORE model predicted mortality and
      morbidity. Age was an important single risk factor predicting mortality.

PMID- 16884984
TI  - The kaolin-activated Thrombelastograph predicts bleeding after cardiac surgery.
AB  - OBJECTIVE: The objective of this study was to determine the relationship of the
      kaolin-activated Thrombelastograph (TEG) with postoperative bleeding and
      laboratory tests of coagulation in the setting of cardiac surgery with the
      routine use of -aminocaproic acid. DESIGN: Prospective observational study.
      SETTING: An adult heart center at a tertiary referral, university hospital.
      PARTICIPANTS: Thirty adult cardiac surgical patients. INTERVENTIONS: The kaolin
      activated TEG, platelet counts, prothrombin times, activated partial
      thromboplastin times, and fibrinogen levels were measured before induction of
      anesthesia, during cardiopulmonary bypass, and on arrival in the intensive care
      unit. Mediastinal and thoracostomy drainage were measured every hour for 4 hours
      after arrival in the intensive care unit. MEASUREMENTS AND MAIN RESULTS:
      Correlation and multivariate linear regression modeling were used to describe
      relationships among coagulation tests, TEG parameters, and early postoperative
      bleeding. The TEG maximum amplitude (MA) parameter correlated well with
      postoperative bleeding (r = -0.6, p = 0.0018), more so than platelet count (r = 
      0.45, p = 0.02), fibrinogen level (r = -0.40, p = 0.06), or prothrombin time (r =
      0.43, p = 0.02). The receiver operating characteristic curve c-index describing
      MA as a predictor for postoperative bleeding is 0.78. Abnormalities in all the
      laboratory test results were associated with an abnormal MA. CONCLUSIONS: In
      conclusion, the kaolin-activated TEG is associated with early coagulopathic
      bleeding. It may reflect the severity of a global coagulopathy affecting both
      platelets and coagulation factors and be a guide to incremental prohemostatic
      therapy in this setting.

PMID- 16884985
TI  - Platelet dysfunction during cardiopulmonary bypass assessed by a novel whole
      blood aggregometer.
AB  - OBJECTIVE: The purpose of this study was to assess perioperative platelet
      function with 2 types of monitors (a whole-blood aggregometer [WBA analyzer;
      Mebanix, Tokyo, Japan]) and the Sonoclot monitor [Sienco, Wheat Ridge, CO]) in
      patients undergoing hypothermic cardiopulmonary bypass (CPB). DESIGN:
      Prospective, observational study. SETTING: Single-center study at a university
      hospital. PARTICIPANTS: Twenty-six patients who underwent coronary artery bypass
      grafting or valve replacement under hypothermic CPB without platelet transfusion
      or fresh frozen plasma administration. INTERVENTIONS: Blood sampling was
      performed at the following time periods: after anesthetic induction, after CPB,
      and on the first postoperative day. These samples were assessed with the WBA
      analyzer and the Sonoclot. MEASUREMENTS AND MAIN RESULTS: Significant attenuation
      of adenosine diphosphate-induced platelet aggregation was detected shortly after
      CPB by 2 WBA analyzer-derived parameters: a decrease in the filtration pressure
      rate and an increase in the platelet aggregatory threshold index. Platelet
      aggregation returned to the preoperative level on the next day. There was no
      correlation between the amount of postoperative mediastinal drainage and defects
      in platelet aggregation. On the other hand, time to peak obtained by the Sonoclot
      did not show any significant changes. CONCLUSIONS: Whole-blood aggregation
      measured with the WBA analyzer detected transient platelet dysfunction shortly
      after CPB, whereas the Sonoclot was less sensitive to this change.

PMID- 16884986
TI  - Autologous blood transfusion for cardiopulmonary bypass: effects of storage
      conditions on platelet function.
AB  - OBJECTIVES: Cardiopulmonary bypass impairs formation of large stable platelet
      aggregates (macroaggregation), although formation of small aggregates
      (microaggregation) is preserved. A factor in the uncertain benefits of
      intraoperative autologous blood transfusion may be the effects of storage on
      platelet function. The effects of citrate preservative and heparinization before
      storage on platelet function was therefore assessed. METHODS: Twenty-seven
      patients undergoing elective coronary artery bypass grafting were randomly
      allocated to have 450 to 1,000 mL of blood taken into CPDA anticoagulant bags
      either before (n = 14) or after heparinization (n = 13). Samples from the
      patients and stored blood were anticoagulated with rhirudin, 200 U/mL. The
      macroaggregatory response to submaximal collagen was measured by impedance
      aggregometry and microaggregation by single platelet counting. RESULTS: During
      macroaggregation, before cardiopulmonary bypass, the ex vivo median
      (interquartile range) response was 16.3 (12.4-18.7) Omega. This decreased 10
      minutes after heparin to 8.9 (3.3-11.0) Omega (p < 0.0001). In the blood bags (in
      vitro), the initial response for nonheparinized blood was 4.8 (0.1-7.5) Omega (p
      < 0.002 v ex vivo) and at end-cardiopulmonary bypass was 2.4 (1.6-8.2) Omega.
      During microaggregation, in vivo heparinization decreased microaggregation both
      ex vivo and in vitro in CPDA blood; the in vitro response of nonheparinized blood
      at end-cardiopulmonary bypass was greater than that seen after in vivo
      heparinization (p < 0.007). No difference in bleeding or transfusion requirements
      was seen. CONCLUSIONS: Collecting blood into CPDA anticoagulant caused a marked
      deterioration in platelet function. This was worse after in vivo heparinization
      and included depression of microaggregation.

PMID- 16884987
TI  - Transfusion triggers in orthotopic liver transplantation: a comparison of the
      thromboelastometry analyzer, the thromboelastogram, and conventional coagulation
      tests.
AB  - OBJECTIVES: The Thromboelastogram (TEG; Haemoscope Corporation, Niles, IL) and
      the ROTEM thromboelastometry analyzer (Pentapharm GmbH, Munich, Germany) are
      coagulation monitors that measure the viscoelastic changes accompanying whole
      blood coagulation generation and lysis. It is not clear whether TEG and ROTEM
      transfusion algorithms suggest similar blood component intervention. This study
      aims to report the extent to which administration of platelets, fresh frozen
      plasma, and cryoprecipitate would be indicated using protocol-dictated
      interventions by the Rotem, TEG, and conventional coagulation screens during
      orthotopic liver transplantation (OLT). DESIGN: Prospective observational study.
      SETTING: University hospital. PARTICIPANTS: Twenty patients undergoing orthotopic
      liver transplantation. INTERVENTIONS: Coagulation was managed with native TEG
      protocols. Additional samples for kaolin TEG, kaolin heparinase TEG, Rotem in
      TEM, Rotem hep-TEM, Rotem fib-TEM, full blood count, prothrombin time, and Clauss
      fibrinogen assays were taken at 5 fixed operative stages. MEASUREMENTS AND MAIN
      RESULTS: Results were reviewed and protocol-indicated interventions recorded.
      There was moderate agreement between Clauss fibrinogen and Rotem fib-TEM assays
      about fulfilling fibrinogen transfusion criteria (kappa = 0.42, p < or = 0.05).
      Agreement between TEG and Rotem to transfuse platelets was fair (Rotem in
      TEM/native heparinase TEG, kappa = 0.33, Rotem in-TEM/kaolin heparinase TEG,
      kappa = 0.28). There was moderate agreement between Rotem in-TEM and prothrombin
      time (kappa = 0.42), and poor agreement between other tests about the point to
      administer fresh frozen plasma. CONCLUSIONS: Transfusion practice is likely to
      differ according to the method of coagulation monitoring used. A prospective case
      matched study using the viscoelastic tests used in this study would be beneficial
      in determining the optimal therapy. Rotem fib-TEM monitoring may improve
      hemostasis management.

PMID- 16884988
TI  - A prospective, randomized platelet-function study of heparinized oxygenators and
      cardiotomy suction.
AB  - OBJECTIVE: The purpose of this study was to determine if substitution of a
      heparin-coated oxygenator and salvaged autologous blood for cardiotomy suction
      would improve platelet function. DESIGN: A prospective, randomized trial.
      SETTING: A large academic medical center. PARTICIPANTS: Sixty adult patients
      undergoing coronary artery bypass graft surgery with cardiopulmonary bypass
      (CPB). INTERVENTIONS: Patients were randomized into 1 of 4 groups in a 2 x 2
      factorial design by oxygenator (heparinized v nonheparinized) and blood salvage
      during CPB (cardiotomy suction v salvaged autologous blood). MEASUREMENTS AND
      MAIN RESULTS: Primary outcome measures were platelet function, glass-bead
      retention, platelet dense-body adenosine triphosphate secretion, platelet-rich
      plasma (PRP) aggregometry, Plateletworks platelet-function analyzer (Helena
      Laboratories Corp, Allen Park, MI), and platelet count. Secondary outcome
      measures were chest-tube drainage and allogeneic blood transfusion requirements.
      All platelet-function tests except thrombin-receptor activator peptide-induced
      PRP aggregometry showed a reduction in platelet function during and immediately
      after CPB (all p < 0.05). The only statistically significant difference in
      platelet-function tests between the groups was the glass-bead assay at 5 minutes
      before discontinuation of CPB (p < 0.05). This difference resolved 10 minutes
      after protamine administration. There were no differences between the groups in
      the amount of blood transfused, chest-tube drainage, and routine laboratory test
      results. CONCLUSIONS: The authors concluded that the effects of these changes to
      the CPB circuit were small and inconsequential in this cohort of patients.

PMID- 16884989
TI  - Transesophageal echocardiography and the intraoperative diagnosis of a right
      pulmonary artery aneurysm.

PMID- 16884990
TI  - Transesophageal echocardiographic-guided percutaneous removal of a pigtail
      catheter from the left atrium.

PMID- 16884991
TI  - Dilutional hypokalemia-induced arrhythmias associated with intraoperative cell
      salvage and reinfusion.

PMID- 16884992
TI  - The use of recombinant-activated factor VII to successfully control postoperative
      critical bleeding after emergency repair of ruptured abdominal aortic aneurysm in
      a noncoagulopathic patient.

PMID- 16884993
TI  - Low-dose recombinant factor VIIa in the management of uncontrolled postoperative
      hemorrhage in cardiac surgery patients.

PMID- 16884994
TI  - Post-cardiopulmonary bypass coagulopathy in a neonate with a family history of
      von Willebrand disease.

PMID- 16884995
TI  - Management of anticoagulation for coronary artery bypass surgery in a patient
      with severe prekallikrein deficiency.

PMID- 16884997
TI  - Case 4--2006: Coexistent hypertrophic obstructive cardiomyopathy, mitral
      stenosis, and coronary artery fistula.

PMID- 16884996
TI  - Tissue Doppler, strain, and strain rate echocardiography: principles and
      potential perioperative applications.

PMID- 16884998
TI  - Pro: near-infrared spectroscopy should be used for all cardiopulmonary bypass.

PMID- 16884999
TI  - Con: all cardiac surgical patients should not have intraoperative cerebral
      oxygenation monitoring.

PMID- 16885000
TI  - Diagnosis and management of persistent pulmonary thromboembolism.

PMID- 16885001
TI  - Lung collapse after induction of anesthesia.

PMID- 16885002
TI  - Addendum to cardiac arrest at 30,000 feet.

PMID- 16885003
TI  - An unusual cause of high airway pressure and inadequate ventilation because of a
      defective connector despite accurate placement of a double-lumen tube.

PMID- 16885004
TI  - Not all glucose clamps are equal.

PMID- 16885005
TI  - Use of ketamine and midazolam cocktail for pericardiectomy at the University of
      Nigeria Teaching Hospital.

PMID- 16885006
TI  - Total anomalous pulmonary venous connection in a patient with situs inversus and
      dextrocardia: which internal jugular vein to cannulate, right or left?

PMID- 16885007
TI  - Peripheral and central contributions to hyperalgesia in irritable bowel syndrome.
AB  - Irritable bowel syndrome (IBS) is a common gastrointestinal disorder seen by
      gastroenterologists. We discuss some recent evidence for potential neural
      mechanisms that could contribute to somatic and visceral hyperalgesia in IBS
      patients. The combination of research studies of human IBS patients and studies
      of rats with delayed rectal hypersensitivity after recovery from experimentally
      induced neonatal colitis strongly suggests a mechanism wherein both primary
      visceral hyperalgesia and secondary widespread cutaneous hyperalgesia are
      dynamically maintained by tonic impulse input from the noninflamed colon and/or
      rectum. The secondary hyperalgesia is likely to be at least partly related to
      sensitization of spinal cord dorsal horn neurons and in this respect might be
      similar to other persistent pain conditions such as fibromyalgia and complex
      regional pain syndrome. PERSPECTIVE: Pain in irritable bowel syndrome is likely
      to be at least partly maintained by peripheral impulse input from the
      colon/rectum and central sensitization, yet it is also highly modifiable by
      psychological factors such as nocebo and placebo effects. A synergistic
      interaction might occur between psychological factors and abnormal afferent
      processing.

PMID- 16885008
TI  - Hypersensitivity: a complex marker for a complex disease.

PMID- 16885009
TI  - Commentary on peripheral and central contributions to hyperalgesia in irritable
      bowel syndrome.

PMID- 16885011
TI  - Persistent pain produces stress-like alterations in hippocampal neurogenesis and
      gene expression.
AB  - Clinical observations have shown that patients with chronic pain are often
      depressed, suggesting the importance of the affective or emotional component of
      pain and its impact on cognition. In this study we investigated pain-induced
      activation of the hippocampus to address possible molecular and cellular events
      that may underlie the comorbidity of chronic pain and depression. Rats received
      either an acute (formalin) or chronic (complete Freund's adjuvant) inflammatory
      stimulus to the hind paw or an acute or chronic immobilization. Results
      demonstrated that pain can alter hippocampal morphology and gene expression.
      Bromodeoxyuridine (BrdU) staining indicated that neurogenesis in the hippocampal
      dentate gyrus was significantly reduced after long-term inflammatory nociception,
      similar to previous observations after various stress models. Important
      activators of nociception-induced spinal central sensitization, the neurokinin-1
      (NK-1) receptor and brain-derived neurotrophic factor (BDNF), have also been
      intimately associated with depressive processes in the limbic system. In situ
      hybridization assay results demonstrated that either pain or stress (acute or
      chronic treatments) reduced the levels of both NK-1 receptor and BDNF mRNAs in
      the cornu ammonis 1-3 sublayers of the hippocampus, suggesting a possible role of
      these neuromediators in processing of pain in higher brain centers. PERSPECTIVE:
      The findings in this study demonstrate that persistent pain induces stress-like
      damaging modulatory effects in the hippocampus, which is one of the limbic
      regions involved in the pathophysiology of depression. Targeting these mechanisms
      (which are potential contributors to the emotional impact of pain) may provide
      novel therapeutic approaches for relieving depression-like aspects of chronic
      pain.

PMID- 16885012
TI  - Sex, gender, and age: contributions to laboratory pain responding in children and
      adolescents.
AB  - A cross-sectional design across late childhood and adolescence examined the
      influence of sex, gender socialization, and age on responses to controlled
      laboratory pain tasks. Healthy children and adolescents (n = 240, 50% female, age
      8 to 18 years) completed the Child Sex Role Inventory, a self-report measure of
      identification with stereotypically masculine and feminine personality traits, as
      an index of gender socialization and participated in pressure, cold pressor, and
      heat pain tasks. Pain tolerance, pain intensity, and bothersomeness of each pain
      task were assessed. Masculinity correlated with lower heat pain ratings in boys
      but not girls. Logistic regression indicated cold pain intensity ratings were
      predicted by sex, gender score, and the age-by-gender score interaction. Heat
      pain intensity was predicted by age, gender score, age-by-gender score
      interaction, and sex-by-gender score. PERSPECTIVE: The current findings support
      closer examination of the influence of gender socialization on young people's
      pain responses and highlight the importance of a multifactorial, developmental
      approach to studying the impact of gender socialization on the emergence of sex
      differences in pain responses after puberty.

PMID- 16885013
TI  - CHF3381, a N-methyl-D-aspartate receptor antagonist and monoamine oxidase-A
      inhibitor, attenuates secondary hyperalgesia in a human pain model.
AB  - CHF3381 is a new low-affinity, noncompetitive N-methyl-D-aspartate (NMDA)
      receptor antagonist and reversible monoamine oxidase-A (MAO-A) inhibitor. The
      analgesic activity of CHF3381 was investigated in the heat-capsaicin human pain
      model and compared with those of gabapentin. Twenty-seven young, healthy male
      volunteers received a single oral dose of CHF3381 (500 mg), gabapentin (1,200
      mg), or placebo in a randomized, double-blind, crossover study design.
      Measurements were done before and 135 to 145 minutes after treatment
      administration and included area of secondary hyperalgesia around the sensitized
      skin of the forearm (45 degrees C for 5 minutes followed by topical capsaicin for
      30 minutes), area of secondary hyperalgesia after thermal sensitization of the
      thigh (45 degrees C for 3 minutes), heat pain detection thresholds (degrees C),
      and pain on a visual analogue scale after long thermal stimulation (45 degrees C
      for 1 minute). Compared with placebo, both gabapentin and CHF3381 significantly
      reduced the area of secondary hyperalgesia on the dominant forearm. Median (and
      interquartile range) percent values over baseline were 86% after placebo (69% to
      100%), 56% (41% to 76%) after gabapentin (P < .001), and 67% (49% to 88%) after
      CHF3381 (P < .009). Both drugs also significantly decreased the area of secondary
      hyperalgesia on the dominant thigh. The other pain variables were not
      significantly affected. Adverse events, mainly fatigue and dizziness, were mild
      to moderate. PERSPECTIVE: This article presents the antihyperalgesic effect of
      CHF3381, a new NMDA receptor antagonist and reversible MAO-A inhibitor, in a
      human pain model and might guide the proper selection of CHF3381 doses to be used
      in Phase 2 studies in patients with neuropathic pain.

PMID- 16885014
TI  - Advanced continuous-contact heat pulse design for efficient temporal summation of
      second pain (windup).
AB  - Temporal summation of second pain or windup (WU(SP)) can be reliably evoked in
      normal human subjects by repetitive heat pulses to the skin at frequencies of
      0.33 Hz or more. This phenomenon is dependent on activation of peripheral C
      nociceptors and central N-methyl-D-aspartate receptors, resulting in windup of C
      fiber-evoked discharges of dorsal horn neurons. Several investigations of heat
      pain summation have used Peltier devices for intermittent-contact heat pulses to
      the skin. This method returns the skin to an adapting temperature between each
      stimulus and can result in distinct first and second pain sensations. An
      alternative method of temporal summation consists of continuous-contact heat
      stimuli by computerized Peltier thermodes that can provide rapid heat pulses.
      Previously used continuous-contact heat pulse trains, however, seemed to lack
      characteristics that result in efficient WU(SP). The present study sought to
      obtain psychophysical evidence that reliable WU(SP) can be elicited with an
      advanced pulse design by using a computerized heat-foil/Peltier thermode. WU(SP)
      was elicited by repetitive thermal stimulation of the hands at frequencies of
      0.33 Hz but not 0.25 and 0.17 Hz. WU(SP) stimuli were either adjusted to resemble
      the heat transfer characteristics of intermittent-contact stimulus trains, or
      they remained unadjusted. The estimated transmission velocity of impulses giving
      rise to second pain and WU(SP) was characteristic of C fibers. More pronounced
      second pain and efficient WU(SP) could be elicited with adjusted than with
      unadjusted heat pulse trains. Thus, specifically designed continuous-contact heat
      pulses can be used to elicit distinct second pain and robust WU(SP), thereby
      providing an efficient psychophysical test of this phenomenon. PERSPECTIVE:
      Temporal summation testing is rapidly becoming a relevant psychophysical tool for
      the study of chronic pain disorders. The results of this study will allow more
      efficient use of currently available constant-contact thermodes for clinical and
      research applications.

PMID- 16885015
TI  - Prevalence and characteristics of breakthrough pain in opioid-treated patients
      with chronic noncancer pain.
AB  - Breakthrough pain is well-characterized in cancer patients but not in patients
      with chronic noncancer pain. We recruited 228 patients with diverse types of
      chronic noncancer pain from 9 pain programs and administered a telephone
      questionnaire with a breakthrough pain assessment algorithm originally designed
      for cancer patients. All patients had controlled baseline pain, and 168 (74%)
      experienced severe to excruciating breakthrough pain. Among those with
      breakthrough pain, the most common syndrome was low back pain (52%), and the
      underlying pathophysiology was variably characterized as somatic (38%),
      neuropathic (18%), visceral (4%), or mixed (40%). A total of 189 different types
      of breakthrough pain were reported. The median number of episodes per day was 2
      (range, <1 to 12). Median time to maximum intensity was 10 minutes (range, 0 to
      180 minutes). Median duration of the breakthrough pain was 60 minutes (range, 1
      to 720 minutes). Patients identified a precipitant for 69% of pains, and 92% of
      these were activity-related. Onset could never be predicted for 45% of pains and
      only sometimes predicted for 31% of pains. Breakthrough pain is highly prevalent
      and varied in this population. Further studies are warranted to clarify whether
      the clinical impact and therapeutic challenges posed by this phenomenon are
      comparable to the cancer population. PERSPECTIVE: This article presents results
      from a survey that demonstrates that breakthrough pain is highly prevalent and
      varied in opioid-treated patients with chronic noncancer pain. These findings
      will assist clinicians in assessing and managing this type of pain.

PMID- 16885016
TI  - Evidence for sex differences in the relationships of pain, mood, and disability.
AB  - Disability demonstrates strong univariate associations with pain and negative
      mood. These relationships are more complex at the multivariate level and might be
      further complicated by sex differences. We investigated sex differences in the
      relationships of pain and negative mood to overall disability and to disability
      in specific functional domains. One hundred ninety-seven consecutive patients
      with low back, myofascial, neck, arthritis, and fibromyalgia pain were recruited
      from university pain clinics and completed measures of disability and negative
      mood. Overall disability and disability in voluntary activities were
      significantly associated with pain and negative mood (factor score) for both
      sexes. Significant sex differences emerged in the strength of the disability-mood
      relationship, with women evincing a stronger relationship. Disability in
      obligatory activities was also significantly related to pain and negative mood
      for both sexes; however, there were no sex differences in the strength of these
      relationships. Mediation analyses indicated that, in men, negative mood partially
      mediated the relationship between pain and both overall disability and disability
      in voluntary activities; mediation was not supported for disability in obligatory
      activities. In women, negative mood fully mediated the relationship between pain
      and all 3 types of disability. These data suggest that disability is more
      directly related to pain in men. In women, the effect of pain on disability
      appears to operate through negative mood. PERSPECTIVE: Results of this study
      demonstrate that sex differences exist in the relationships of pain, mood, and
      disability. Men and women might thus benefit from treatment interventions that
      differentially target these variables.

PMID- 16885017
TI  - Joint mobilization reduces hyperalgesia associated with chronic muscle and joint
      inflammation in rats.
AB  - Joint mobilization is a common treatment used by healthcare professions for
      management of a variety of painful conditions, including inflammatory joint and
      muscle pain. We hypothesized that joint mobilization would reduce the bilateral
      hyperalgesia induced by muscle and joint inflammation. Mechanical hyperalgesia
      was measured by examining the mechanical withdrawal threshold of the rat's paw
      before and after induction of inflammation with 3% carrageenan (gastrocnemius
      muscle) or 3% kaolin/carrageenan (knee joint), and for 1 hour after knee joint
      mobilization. The mobilization consisted of rhythmically flexing and extending
      the knee joint to the end of range of extension while the tibia was
      simultaneously moved in an anterior to posterior direction. A bilateral decrease
      in mechanical withdrawal thresholds occurred 1, 2, and 4 weeks after inflammation
      of the knee joint or muscle. In animals with muscle inflammation, mobilization of
      the knee joint increased the mechanical withdrawal threshold bilaterally when
      given 1, 2, or 4 weeks after inflammation. However, in animals with knee joint
      inflammation, mobilization of the knee joint at 4 weeks increased the mechanical
      withdrawal threshold but had no effect when administered 1 or 2 weeks after
      inflammation. Therefore, joint mobilization reduces hyperalgesia induced by
      chronic inflammation of muscle and joint. PERSPECTIVE: This article shows that
      unilateral joint mobilization reduces bilateral hyperalgesia induced by chronic
      muscle or joint inflammation. Understanding the pain conditions in which
      mobilization produces an analgesic effect should assist the clinician in
      selecting appropriate treatment techniques. The bilateral effect suggests that
      central mechanisms could mediate the analgesia.

PMID- 16885018
TI  - Bevel design and not needle length determines the pain experience in patients
      receiving injections.

PMID- 16885019
TI  - Enhanced histone acetylation and transcription: a dynamic perspective.
AB  - Stably enhanced histone acetylation has long been regarded as a condition of
      transcriptionally active genes. Recent papers suggest a more dynamic model, with
      rapid turnover of acetylation observed at nontranscribing "poised" genes and
      shown to be an important determinant of transcriptional efficiency upon gene
      induction. Are these "special cases," restricted to specific genes and specific
      types of histone modifications, or could the entire panoply of histone
      modifications associated with transcription now be revisited with a much more
      dynamic perspective?

PMID- 16885020
TI  - Controlling the elongation phase of transcription with P-TEFb.
AB  - The positive transcription elongation factor b (P-TEFb) is a cyclin-dependent
      kinase that controls the elongation phase of transcription by RNA polymerase II
      (RNAPII). This process is made possible by the reversal of effects of negative
      elongation factors that include NELF and DSIF. In complex organisms, elongation
      control is critical for the regulated expression of most genes. In those
      organisms, the function of P-TEFb is influenced negatively by HEXIM proteins and
      7SK snRNA and positively by a variety of recruiting factors. Phylogenetic
      analyses of the components of the human elongation control machinery indicate
      that the number of mechanisms utilized to regulate P-TEFb function increased as
      organisms developed more complex developmental patterns.

PMID- 16885021
TI  - Destruction of Claspin by SCFbetaTrCP restrains Chk1 activation and facilitates
      recovery from genotoxic stress.
AB  - We show that Claspin, an adaptor protein required for Chk1 activation, becomes
      degraded at the onset of mitosis. Claspin degradation was triggered by its
      interaction with, and ubiquitylation by, the SCFbetaTrCP ubiquitin ligase. This
      interaction was phosphorylation dependent and required the activity of the Plk1
      kinase and the integrity of a betaTrCP recognition motif (phosphodegron) in the N
      terminus of Claspin. Uncoupling of Claspin from betaTrCP by mutating the
      conserved serines in Claspin's phosphodegron or by knocking down betaTrCP
      stabilized Claspin in mitosis, impaired Chk1 dephosphorylation, and delayed G2/M
      transition during recovery from cell cycle arrest imposed by DNA damage or
      replication stress. Moreover, the inability to degrade Claspin allowed partial
      reactivation of Chk1 in cells exposed to DNA damage after passing the G2/M
      transition. Our data suggest that degradation of Claspin facilitates timely
      reversal of the checkpoint response and delineates the period permissive for Chk1
      activation during cell cycle progression.

PMID- 16885022
TI  - SCFbetaTrCP-mediated degradation of Claspin regulates recovery from the DNA
      replication checkpoint response.
AB  - During replicative stress, Claspin mediates the phosphorylation and consequent
      activation of Chk1 by ATR. We found that during recovery from the DNA replication
      checkpoint response, Claspin is degraded in a betaTrCP-dependent manner. In vivo,
      Claspin is phosphorylated in a canonical DSGxxS degron sequence, which is typical
      of betaTrCP substrates. Phosphorylation of Claspin is mediated by Plk1 and is
      essential for binding to betaTrCP. In vitro ubiquitylation of Claspin requires
      betaTrCP, Plk1, and an intact DSGxxS degron. Significantly, expression of a
      stable Claspin mutant unable to bind betaTrCP prolongs the activation of Chk1,
      thereby attenuating the recovery from the DNA replication stress response and
      significantly delaying entry into mitosis. Thus, the SCFbetaTrCP-dependent
      degradation of Claspin is necessary for the efficient and timely termination of
      the DNA replication checkpoint. Importantly, in response to DNA damage in G2,
      Claspin proteolysis is inhibited to allow the prompt reestablishment of the
      checkpoint.

PMID- 16885023
TI  - Rad17 phosphorylation is required for claspin recruitment and Chk1 activation in
      response to replication stress.
AB  - The ATR-mediated checkpoint is not only critical for responding to genotoxic
      stress but also essential for cell proliferation. The RFC-related checkpoint
      protein Rad17, a phosphorylation substrate of ATR, is critical for ATR-mediated
      checkpoint signaling and cell survival. Here, we show that phosphorylation of
      Rad17 by ATR is important for genomic stability and restraint of S phase but is
      not essential for cell survival. The phosphomutant Rad17AA exhibits distinct
      defects in hydroxyurea- (HU) and ultraviolet- (UV) induced Chk1 activation,
      indicating that separate Rad17 functions are required differently in response to
      different types of replication interference. Although cells expressing Rad17AA
      can initiate Chk1 phosphorylation after HU treatment, they fail to sustain Chk1
      phosphorylation after withdrawal of HU and are profoundly sensitive to HU.
      Importantly, we found that phosphorylated Rad17 interacts with Claspin and
      regulates its phosphorylation. These findings reveal a phosphorylation-dependent
      function of Rad17 in an ATR-Rad17-Claspin-Chk1-signaling cascade that responds to
      specific replication stress.

PMID- 16885024
TI  - Structural basis for specificity in the poxvirus topoisomerase.
AB  - Although smallpox has been eradicated from the human population, it is presently
      feared as a possible agent of bioterrorism. The smallpox virus codes for its own
      topoisomerase enzyme that differs from its cellular counterpart by requiring a
      specific DNA sequence for activation of catalysis. Here we present crystal
      structures of the smallpox virus topoisomerase enzyme bound both covalently and
      noncovalently to a specific DNA sequence. These structures reveal the basis for
      site-specific DNA recognition, and they explain how catalysis is likely activated
      by formation of a specific enzyme-DNA interface. Unexpectedly, the poxvirus
      enzyme uses a major groove binding alpha helix that is not present in the human
      enzyme to recognize part of the core recognition sequence and activate the enzyme
      for catalysis. The topoisomerase-DNA complex structures also provide a three
      dimensional framework that may facilitate the rational design of therapeutic
      agents to treat poxvirus infections.

PMID- 16885025
TI  - Head module control of mediator interactions.
AB  - Yeast Mediator proteins interacting with Med17(Srb4) have been expressed at a
      high level with the use of recombinant baculoviruses and recovered in homogeneous
      form as a seven subunit, 223 kDa complex. Electron microscopy and single-particle
      analysis identify this complex as the Mediator head module. The recombinant head
      module complements "headless" Mediator for the initiation of transcription in
      vitro. The module interacts with an RNA polymerase II-TFIIF complex, but not with
      the polymerase or TFIIF alone. This interaction is lost in the presence of a DNA
      template and associated RNA transcript, recapitulating the release of Mediator
      that occurs upon the initiation of transcription. Disruption of the head module
      in a temperature-sensitive mutant in vivo leads to the release of middle and tail
      modules from a transcriptionally active promoter. The head module evidently
      controls Mediator-RNA polymerase II and Mediator-promoter interactions.

PMID- 16885026
TI  - Locus control region transcription plays an active role in long-range gene
      activation.
AB  - Activation of eukaryotic genes often relies on remote chromatin determinants. How
      these determinants function remains poorly understood. The hGH gene is activated
      by a 5'-remote locus control region (LCR). Pituitary-specific DNase I
      hypersensitive site I (HSI), the dominant hGH LCR element, is separated from the
      hGH-N promoter by a 14.5 kb span that encompasses the B-lymphocyte-specific CD79b
      gene. Here, we describe a domain of noncoding Pol II transcription in pituitary
      somatotropes that includes the hGH LCR and adjacent CD79b locus. This entire "LCR
      domain of transcription" is HSI [corrected] dependent and terminates 3' to CD79b,
      leaving a gap in transcription between this domain and the target hGH-N promoter.
      Insertion of a Pol II terminator within the LCR blocks CD79b transcription and
      represses hGH-N expression. These data document an essential role for LCR
      transcription in long-range control, link "bystander"CD79b transcription to this
      process, and support a unique model for locus activation.

PMID- 16885027
TI  - Structural basis for CoREST-dependent demethylation of nucleosomes by the human
      LSD1 histone demethylase.
AB  - Histone methylation regulates diverse chromatin-templated processes, including
      transcription. Many transcriptional corepressor complexes contain lysine-specific
      demethylase 1 (LSD1) and CoREST that collaborate to demethylate mono- and
      dimethylated H3-K4 of nucleosomes. Here, we report the crystal structure of the
      LSD1-CoREST complex. LSD1-CoREST forms an elongated structure with a long stalk
      connecting the catalytic domain of LSD1 and the CoREST SANT2 domain. LSD1
      recognizes a large segment of the H3 tail through a deep, negatively charged
      pocket at the active site and possibly a shallow groove on its surface. CoREST
      SANT2 interacts with DNA. Disruption of the SANT2-DNA interaction diminishes
      CoREST-dependent demethylation of nucleosomes by LSD1. The shape and dimension of
      LSD1-CoREST suggest its bivalent binding to nucleosomes, allowing efficient H3-K4
      demethylation. This spatially separated, multivalent nucleosome binding mode may
      apply to other chromatin-modifying enzymes that generally contain multiple
      nucleosome binding modules.

PMID- 16885029
TI  - Polypyrimidine tract binding protein regulates IRES-mediated gene expression
      during apoptosis.
AB  - During apoptosis there is a substantial reduction in the rate of protein
      synthesis, and yet some mRNAs avoid this translational inhibition. To determine
      the impact that receptor-mediated cell death has on the translational efficiency
      of a large number of mRNAs, translational profiling was performed on MCF7 cells
      treated with the apoptosis-inducing ligand TRAIL. Our data indicate that
      approximately 3% of mRNAs remain associated with the polysomes in apoptotic
      cells, and genes that are involved in transcription, chromatin
      modification/remodeling, and the Notch signaling pathway are particularly
      prevalent among the mRNAs that evade translational inhibition. Internal ribosome
      entry segments (IRESs) were identified in several of the mRNAs that remained
      associated with the polysomes during apoptosis, and, importantly, these IRESs
      functioned efficiently in apoptotic cells. Finally, the data showed that
      polypyrimidine tract binding protein (PTB, a known IRES trans-acting factor or
      ITAF) is pivotal in regulating the apoptotic process by controlling IRES
      function.

PMID- 16885028
TI  - The EF-G-like GTPase Snu114p regulates spliceosome dynamics mediated by Brr2p, a
      DExD/H box ATPase.
AB  - Binding of a pre-mRNA substrate triggers spliceosome activation, whereas the
      release of the mRNA product triggers spliceosome disassembly. The mechanisms that
      underlie the regulation of these rearrangements remain unclear. We find evidence
      that the GTPase Snu114p mediates the regulation of spliceosome activation and
      disassembly. Specifically, both unwinding of U4/U6, required for spliceosome
      activation, and disassembly of the postsplicing U2/U6.U5.intron complex are
      repressed by Snu114p bound to GDP and derepressed by Snu114p bound to GTP or
      nonhydrolyzable GTP analogs. Further, similar to U4/U6 unwinding, spliceosome
      disassembly requires the DExD/H box ATPase Brr2p. Together, our data define a
      common mechanism for regulating and executing spliceosome activation and
      disassembly. Although sequence similarity with EF-G suggests Snu114p functions as
      a molecular motor, our findings indicate that Snu114p functions as a classic
      regulatory G protein. We propose that Snu114p serves as a signal-dependent switch
      that transduces signals to Brr2p to control spliceosome dynamics.

PMID- 16885030
TI  - Crystal structure of the PP2A phosphatase activator: implications for its PP2A
      specific PPIase activity.
AB  - PTPA, an essential and specific activator of protein phosphatase 2A (PP2A),
      functions as a peptidyl prolyl isomerase (PPIase). We present here the crystal
      structures of human PTPA and of the two yeast orthologs (Ypa1 and Ypa2),
      revealing an all alpha-helical protein fold that is radically different from
      other PPIases. The protein is organized into two domains separated by a groove
      lined by highly conserved residues. To understand the molecular mechanism of PTPA
      activity, Ypa1 was cocrystallized with a proline-containing PPIase peptide
      substrate. In the complex, the peptide binds at the interface of a peptide
      induced dimer interface. Conserved residues of the interdomain groove contribute
      to the peptide binding site and dimer interface. Structure-guided mutational
      studies showed that in vivo PTPA activity is influenced by mutations on the
      surface of the peptide binding pocket, the same mutations that also influenced
      the in vitro activation of PP2Ai and PPIase activity.

PMID- 16885041
TI  - Programming a hematopoietic stem cell donor: the evolution of a project over
      time.

PMID- 16885031
TI  - Destruction or potentiation of different prions catalyzed by similar Hsp104
      remodeling activities.
AB  - Yeast prions are protein-based genetic elements that self-perpetuate changes in
      protein conformation and function. A protein-remodeling factor, Hsp104, controls
      the inheritance of several yeast prions, including those formed by Sup35 and
      Ure2. Perplexingly, deletion of Hsp104 eliminates Sup35 and Ure2 prions, whereas
      overexpression of Hsp104 purges cells of Sup35 prions, but not Ure2 prions. Here,
      we used pure components to dissect how Hsp104 regulates prion formation, growth,
      and division. For both Sup35 and Ure2, Hsp104 catalyzes de novo prion nucleation
      from soluble, native protein. Using a distinct mechanism, Hsp104 fragments both
      prions to generate new prion assembly surfaces. For Sup35, the fragmentation
      endpoint is an ensemble of noninfectious, amyloid-like aggregates and soluble
      protein that cannot replicate conformation. In vivid distinction, the endpoint of
      Ure2 fragmentation is short prion fibers with enhanced infectivity and self
      replicating ability. These advances explain the distinct effects of Hsp104 on the
      inheritance of the two prions.

PMID- 16885032
TI  - Photoactivated phytochrome induces rapid PIF3 phosphorylation prior to proteasome
      mediated degradation.
AB  - Following light-induced nuclear translocation, specific members of the
      phytochrome (phy) photoreceptor family (phyA to phyE) interact with bHLH
      transcription factors, such as PIF3, and induce changes in target-gene
      expression. The biochemical mechanism comprising signal transfer from phy to PIF3
      has remained undefined but results in rapid degradation of PIF3. We provide
      evidence that photoactivation of phy induces rapid in vivo phosphorylation of
      PIF3 preceding degradation. Both phyA and phyB redundantly induce this PIF3
      phosphorylation, as well as nuclear speckle formation and degradation, by direct
      interaction with PIF3 via separate binding sites. These data suggest that phy
      induced phosphorylation of proteins such as PIF3 may represent the primary
      intermolecular signaling transaction of the activated photoreceptor, tagging the
      target protein for proteosomal degradation, possibly in nuclear speckles.

PMID- 16885042
TI  - Thalidomide versus placebo in myeloid metaplasia with myelofibrosis: a
      prospective, randomized, double-blind, multicenter study.
AB  - BACKGROUND AND OBJECTIVES: In non-randomized studies, thalidomide appeared to be
      effective in myeloid metaplasia with myelofibrosis (MMM). We compared thalidomide
      to placebo for treatment of anemia in MMM. DESIGN AND METHODS: A prospective
      phase II B, randomized double-blind multicenter trial comparing thalidomide 400
      mg/d with placebo for 180 days was conducted in 52 anemic patients (hemoglobin
      pounds Sterling 9 g/dL or transfused). The main outcome measure was a 2 g/L
      increase in hemoglobin or 20% reduction in transfusions. RESULTS: In the
      thalidomide group only 10 patients completed 6 months of treatment. At 180 days,
      in an intention-to-treat analysis, no difference was observed between the
      thalidomide and placebo groups as regards improvement of hemoglobin levels (one
      patient in each group) or reduction of red blood cell transfusions (three vs five
      patients, respectively). The spleen size, determined by ultrasonography,
      increased significantly less in the thalidomide group than in the placebo group
      (p < 0.05). Thalidomide had no apparent benefit on the Dupriez score, the
      severity score, survival, death, or any other clinical or biological parameter.
      Somnolence, gastro-intestinal signs, weight gain, and edema were significantly
      more frequent in the thalidomide group. Outpatient discontinuation of thalidomide
      was significantly correlated with a high severity score > 4 (odds ratio, OR = 16;
      p < 0.01), and g-glutamyl transferase levels > 40 IU/L (OR = 12; p < 0.05).
      INTERPRETATION AND CONCLUSIONS: Thalidomide (200-400 mg/d) does not demonstrate
      substantial efficacy in anemic MMM patients. The natural history of disease in
      the placebo group revealed spontaneous periods of remission of anemia. Tolerance
      of thalidomide was significantly correlated wih the severity and liver
      involvement of the disease.

PMID- 16885043
TI  - The course of severe autoimmune thrombocytopenia in patients not undergoing
      splenectomy.
AB  - BACKGROUND AND OBJECTIVES: Splenectomy is the most effective treatment for
      patients with severe autoimmune thrombocytopenia (AITP) who do not have a
      spontaneous or drug- induced remission. However, this treatment has some short
      and long term risks. There is no consensus on the indications and optimal timing
      of splenectomy, since it is unknown up to which time from onset of symptoms a
      remission can be expected without splenectomy. DESIGN AND METHODS: We studied the
      incidence of complete or partial remissions in a cohort of 114 adult patients (68
      women, 46 men, median age 49.8 years, interquartile range 28.3-68.4) with severe
      AITP (platelet count < 20x10(9)/L at diagnosis) using Kaplan Meier analysis.
      Patients who underwent splenectomy during the observation period were censored at
      the time of splenectomy. RESULTS: The probability of a complete remission was 61%
      and that of at least a partial remission was 86% at 5 years. The incidence of
      complete remission was highest within the first 6 months (30%), but increased up
      to 53% between 6 months and 3 years after diagnosis. The probability of a
      remission was not related to age, gender, or the presence or absence of platelet
      antibodies, but was higher in patients with an acute onset of symptoms in
      comparison to those with an insidious onset (p = 0.0003). The chance of a late
      remission was higher in patients with an insidious onset of disease.
      INTERPRETATION AND CONCLUSIONS: These data indicate that splenectomy may be
      delayed for up to 3 years, in particular in those patients whose AITP has had an
      insidious onset.

PMID- 16885044
TI  - Venous thromboembolism in very elderly patients: findings from a prospective
      registry (RIETE).
AB  - BACKGROUND AND OBJECTIVES: Elderly patients with venous thromboembolism (VTE)
      have an increased rate of bleeding complications on therapeutic doses of
      anticoagulant therapy. DESIGN AND METHODS: Using data in RIETE, an international
      registry of consecutive patients with objectively confirmed, symptomatic acute
      VTE, we analyzed the clinical characteristics and outcome within 90 days of
      therapy of all enrolled patients aged > or = 80 years old. RESULTS: Of the 13,011
      patients with VTE enrolled in RIETE up tp September 2005, 2890 (22%) were aged >
      or = 80 years old. During the study period 99 patients (3.4%) aged > or = 80
      years, and 212 aged < 80 years (2.1%) had major bleeding events (odds ratio: 1.7;
      95% CI: 1.3-2.1). Fatal bleeding occurred in 0.8% and 0.4%, respectively (odds
      ratio: 2.0; 95% CI: 1.2-3.4). The incidence of recurrent VTE was 2.1% and 2.8%.
      However, 3.7% of patients > or = 80 years and 1.1% < 80 years died of pulmonary
      embolism (PE) (odds ratio: 3.6; 95% CI: 2.7-4.7). On multivariate analysis,
      patients > or = 80 years with symptomatic PE, heart failure, long-term therapy
      with low-molecular-weight heparin (LMWH) or a vena cava filter had an increased
      risk of recurrent VTE. Those with recent bleeding, abnormal renal function, use
      of corticosteroids or long-term therapy with LMWH had an increased risk of major
      bleeding. INTERPRETATION AND CONCLUSIONS: In patients aged > or = 80 years old
      the 3.4% incidence of major bleeding exceeded the 2.1% incidence of VTE
      recurrences. However, the 3.7% incidence of fatal PE outweighed the 0.8% of fatal
      bleeding. Thus, there seems to be more reason to be concerned about fatal PE than
      about bleeding in elderly patients with VTE.

PMID- 16885045
TI  - Out of hospital treatment with subcutaneous low molecular weight heparin in
      patients with acute deep-vein thrombosis: a prospective study in daily practice.
AB  - BACKGROUND AND OBJECTIVES: Clinical trials have demonstrated that initial
      outpatient treatment is safe and effective in patients with deep vein thrombosis
      (DVT). Considering the relative lack of literature-based evidence on outpatient
      low molecular weight heparin (LMWH) treatment in daily practice this study
      prospectively evaluated the implementation of a protocol for full outpatient
      treatment of DVT in a non-teaching hospital. DESIGN AND METHODS: Consecutive
      patients with objectively demonstrated DVT were treated on an outpatient basis
      with subcutaneous nadroparin injections for at least 5 days and oral
      anticoagulant treatment for at least 3 months. RESULTS: In 294 of 309 (95%)
      consecutive patients with proven DVT, nadroparin could be started on a fully
      outpatient basis. During initial LMWH treatment one patient had to be
      hospitalized because of objectively proven pulmonary embolism (PE), and one
      patient developed a major bleeding complication. Overall, during 3 months follow
      up recurrent venous thromboembolism (VTE) occurred in nine patients (3.1%; 95 CI
      1.1 to 5.1), four patients experienced a major non-fatal hemorrhage (1.4%; 95 CI
      0.04 to 2.7) and ten patients died (3.4%; 95% CI 1.3 to 5.5) of whom seven with
      disseminated malignancy, but none of fatal PE. INTERPRETATION AND CONCLUSIONS:
      Out of hospital initiation of anticoagulant treatment with LMWH is safe and
      effective in the overall majority of patients (95%) with objectively proven DVT.
      We believe that these results are relevant to both clinicians and health care
      providers in view of the feasibility of home treatment in nearly all patients.

PMID- 16885046
TI  - The role of HLA mismatch, splenectomy and recipient Epstein-Barr virus
      seronegativity as risk factors in post-transplant lymphoproliferative disorder
      following allogeneic hematopoietic stem cell transplantation.
AB  - BACKGROUND AND OBJECTIVES: Post-transplant lymphoproliferative disorder (PTLD)
      following allogeneic hematopioetic stem cell transplantation (HSCT) is a
      fulminant disease with high mortality. The objective of this study was to
      determine risk factors in PTLD following HSCT in order to identify high-risk
      patients for surveillance, prophylaxis and treatment. DESIGN AND METHODS: Five
      hundred and fifty-three HSCT patients transplanted at Karolinska University
      Hospital in Huddinge between 1996 and 2004 were investigated retrospectively and
      14 cases of PTLD were identified. Diseased patients were evaluated concerning
      transplantation procedure, PTLD diagnosis, treatment and outcome. Factors
      significant in univariate analysis were included in logistic regression
      multivariate analysis. RESULTS: The incidence of PTLD was 2.5% and the median
      onset of PTLD was 78 days post-transplantation. Only two PTLD patients survived.
      The most common therapy was anti-B-lymphocyte antibodies. Statistical analysis
      showed HLA mismatch (p < 0.001), mismatch in Epstein-Barr virus (EBV) serology (p
      < 0.001) and splenectomy (p = 0.006) to be risk factors associated with PTLD.
      Indeed, among 387 patients with no risk factors only one developed PTLD (0.26%).
      Patients with one risk factor had a probability of developing PTLD of 8.2% and
      those with two risk factors, a probability of 35.7%. INTERPRETATION AND
      CONCLUSIONS: We propose a strategy for dealing with PTLD. Patients without risk
      factors need not be monitored routinely. HSCT patients with one or more risk
      factors should be monitored weekly by polymerase chain reaction of EBV DNA, and
      for patients with two or more risk factors EBV-specific cytotoxic T-lymphocytes
      should be held in readiness before initiating the transplantation procedure.

PMID- 16885047
TI  - The epidemiology of fungal infections in patients with hematologic malignancies:
      the SEIFEM-2004 study.
AB  - BACKGROUND AND OBJECTIVES: The aim of this study was to evaluate the incidence
      and outcome of invasive fungal infections (IFI) in patients with hematologic
      malignancies. DESIGN AND METHODS: This was a retrospective cohort study of
      patients admitted between 1999 and 2003 to 18 hematology wards in Italy. Each
      participating center provided information on all patients with newly diagnosed
      hematologic malignancies admitted during the survery period and on all episodes
      of IFI experienced by these patients. RESULTS: The cohort was formed of 11,802
      patients with hematologic malignacies: acute leukemia (myeloid 3012, lymphoid
      1173), chronic leukemia (myeloid 596, lymphoid 1104), lymphoma (Hodgkin's 844,
      non-Hodgkin's 3457), or multiple myeloma (1616). There were 538 proven or
      probable IFI (4.6%); 373 (69%) occurred in patients with acute myeloid leukemia.
      Over half (346/538) were caused by molds (2.9%), in most cases Aspergillus spp.
      (310/346). The 192 yeast infections (1.6%) included 175 cases of candidemia.
      Overall and IFI-attributable mortality rates were 2% (209/11802) and 39%
      (209/538), respectively. The highest IFI-attributable mortality rates were
      associated with zygomycosis (64%) followed by fusariosis (53%), aspergillosis
      (42%), and candidemia (33%). INTERPRETATION AND CONCLUSIONS: Patients with
      hematologic malignancies are currently at higher risk of IFI caused by molds than
      by yeasts, and the incidence of IFI is highest among patients with acute myeloid
      leukemia. Aspergillus spp are still the most common pathogens, followed by
      Candida spp. Other agents are rare. The attributable mortality rate for
      aspergillosis has dropped from 60-70% to approximately 40%. Candidemia-related
      mortality remains within the 30-40% range reported in literature although the
      incidence has decreased.

PMID- 16885048
TI  - Combination erythropoietin-hydroxyurea therapy in sickle cell disease: experience
      from the National Institutes of Health and a literature review.
AB  - Erythropoietin is being used more widely in the management of sickle cell disease
      (SCD, inclusive of homozygous sickle beta, SS, and compound heterozygous sickle
      beta thalassemia, Sbeta0 thal), often in conjunction with hydroxyurea (HU).
      Herein, we summarize the published experience with erythropoietin use in SCD, in
      39 patients (SS, n = 30; Sb0 thal, n = 9) who were treated between 1990 and 1996;
      and in 13 patients with sickle syndromes (SS, n = 12, compound heterozygous SC
      disease, n = 1) who were treated with erythropoietin or darbepoietin at the
      National Institutes of Health (NIH) since 2002. The dose range of erythropoietin
      for SCD in the published series, at a median of > 200 U/Kg/dose, is higher than
      that used in end-stage renal disease. The median duration of erythropoietin
      therapy was > or =3 months, with minimal reported side-effects. At the NIH, the
      median age of sickle syndrome patients who received erythropoietin or
      darbepoietin (both referred to as EPO in the NIH series) was 51 (24 to 70) years;
      12/13 patients had sickle-associated pulmonary hypertension. Eleven out of the 13
      patients were treated with both HU and EPO for > 4 months (median of 11 months on
      EPO) without complication. Of the 13 patients, five (all SS) with pulmonary
      hypertension were given EPO for reticulocytopenia (< 100,000/mL) on HU; 5/13
      patients (all SS), with pulmonary hypertension, were given EPO and HU
      concurrently, in the light of an estimated glomerular filtration rate of < 80
      mL/minute. Three of the 13 patients (2 SS, 1 SC) were treated with EPO for
      miscellaneous reasons. Hematologic responses, detailed herein, suggest that EPO
      therapy may allow more aggressive HU dosing in high-risk SCD patients and in the
      setting of mild renal insufficiency, common to the aging sickle cell population.
      Furthermore EPO appears to be safe in SCD, particularly when used in conjunction
      with HU. We outline our current therapeutic strategy for EPO use in SCD.

PMID- 16885049
TI  - Molecular and clinical correlates in iron overload associated with mutations in
      ferroportin.
AB  - Mutations in ferroportin (Fpn) result in iron overload. We correlate the behavior
      of three Fpn mutants in vitro with patients' phenotypes. Patients with Fpn
      mutations A77D or N174I showed macrophage iron loading. In cultured cells,
      FpnA77D did not reach the cell surface and cells did not export iron. Fpn mutant
      N174I showed plasma membrane and intracellular localization, and did not
      transport iron. Fpn mutation G80S was targeted to the cell surface and was
      transport competent, however patients showed macrophage iron. We suggest that
      FpnG80S represents a class of Fpn mutants whose behavior in vitro does not
      explain the patients' phenotype.

PMID- 16885050
TI  - Osteonecrosis after allogeneic stem cell transplantation in childhood. A case
      control study in Italy.
AB  - A case-control study was conducted among Italian children treated with a stem
      cell transplant (SCT). Cases (n = 43) were allogeneic recipients with
      osteonecrosis, and the controls (n = 129) were matched to the corresponding cases
      on the basis of survival, SCT center and date of transplant. Univariate analysis
      showed that older age at SCT (OR 1.39; 95% CI 1.24-1.57), total body irradiation
      (TBI) (OR 5.73; 95% CI 2.38-13.83), chronic graft-versus-host disease (GvHD) (OR
      4.31; 95% CI 2.05-9.07), and duration of steroid treatment after SCT (OR 1.118;
      95% CI 1.034-1.209) were statistically correlated with osteonecrosis. However,
      multivariate analysis revealed that the only factors that were significantly
      associated with osteonecrosis were older age at SCT (p = 0.0001), TBI (p = 0.001)
      and chronicGvHD (p = 0.001).

PMID- 16885051
TI  - An acquired translocation in JAK2 Val617Phe-negative essential thrombocythemia
      associated with autosomal spread of X-inactivation.
AB  - The acquired mutation Val617Phe in the tyrosine kinase JAK2 was recently
      identified in most but not all patients with classical myeloproliferative
      disorders. We describe a cytogenetic and molecular study of a JAK2Val617Phe
      negative case of essential thrombocythemia harboring the acquired translocation
      t(X;5)(q13;q33). We show that this involves the inactive X-chromosome and is
      associated with silencing of autosomal genes within the adjacent 5q minus
      syndrome common deleted region. This is the first documented example of autosomal
      gene silencing adjacent to an X-autosome breakpoint in human malignancy and such
      a mechanism may underlie the pathogenesis of related disorders with
      translocations involving Xq13.

PMID- 16885052
TI  - Methodological approach to minimal residual disease detection by flow cytometry
      in adult B-lineage acute lymphoblastic leukemia.
AB  - A flow cytometric approach to minimal residual disease (MRD) monitoring useful in
      childhood B-lineage acute lymphoblastic leukemia (ALL) is discussed here in the
      context of ALL in adults. Of 64 leukemia samples analyzed, 95.3% had at least one
      abnormal phenotype (57.3% had two or more) as compared to physiologic B-cell
      precursors in adult bone marrow. The method was sensitive enough to detect one
      leukemic cell among 10,000 normal cells in 16/19 experiments (84.2%). Blast
      phenotypes were stable in culture and at relapse, and were useful for MRD
      monitoring in patients. Marker combinations for childhood ALL are also applicable
      to adult cases.

PMID- 16885053
TI  - Clinical features and outcome of familial chronic lymphocytic leukemia.
AB  - The prognostic impact of the presence of a familial trait was analyzed in 1449
      patient with chronic lymphocytic leukemia (CLL). A family history of hematologic
      malignancy (HM) was identified in 181 cases (12.5%) and recorded more frequently
      among female than male patients (HM: p < 0.05; CLL: p < 0.05). The relative was
      affected by CLL in 89 cases (6%). Familial and sporadic cases showed non
      statistically different proportions of advanced stages (10.8 vs 7.1%) and
      patients requiring therapy (55 vs 60%) and a similar survival probability at 10
      years (67 vs 66%). These data suggest that in CLL the presence of a familial
      trait does not imply an adverse prognosis.

PMID- 16885054
TI  - High-dose chemotherapy followed by autologous hematopoietic stem cell
      transplantation for adult histiocytic disorders with central nervous system
      involvement.
AB  - We postulated that high-dose chemotherapy (HDC) followed by peripheral autologous
      hematopoietic stem cell transplantation might help to control refractory central
      nervous system (CNS) histiocytic disorders. Six patients with histiocytic CNS
      involvement were treated in this way. Two patients achieved non-active disease
      status, although one relapsed at 84 months. Two patients had regressive disease,
      one of whom progressed at 21 months. One patient had progressive disease at 14
      months. One patient had extra-CNS progression but CNS regression. After a median
      follow-up of 22.4 months, only one of the six patients still has non-active
      disease. Treatment was effective on craniofacial and space-occupying brainstem
      lesions, and was ineffective on neurodegenerative lesions.

PMID- 16885055
TI  - Expression of cellular prion protein on platelets from patients with gray
      platelet or Hermansky-Pudlak syndrome and the protein's association with alpha
      granules.
AB  - The cellular prion protein (PrPc) is a membrane glycoprotein expressed on many
      human cells including platelets. We investigated the cellular localization of
      platelet PrPc. In resting platelets most PrPc was localized inside the cells. The
      correlation of PrPc and P-selectin surface up-regulation after platelet
      activation suggested its association with alpha-granules. This was confirmed by
      normal expression of PrPc on Hermansky-Pudlak syndrome platelets, which lack
      dense granules, and failure of gray platelet syndrome platelets, which lack alpha
      granules, to up-regulate PrPc. Our results warrant further studies on the role of
      platelet PrPc in the transmission of prion diseases by blood transfusion.

PMID- 16885056
TI  - An 18-case outbreak of drug-resistant Pseudomonas aeruginosa bacteriemia in
      hematology patients.
AB  - We retrospectively identified an outbreak of 18 episodes of P. aeruginosa
      bacteriemia in 17 patients with hematologic malignancies in 2004. All strains
      were ticarcillin I/R, 77% ciprofloxacin I/R, 72% ceftazidime I/R, 72% amikacin
      I/R and 50% imipenem I/R. The outbreak was multiclonal. Colistin was employed for
      documented therapy in ten cases including seven in which it was the only active
      drug. Outcomes were resolution of infection in 12 out of 18 episodes (67%), and
      death in six cases, five (25%) of which were attributable to the infection.
      Colistin was useful even in highly resistant strains and the efficacy of
      antibacterial therapy was similar (57%)in bacteriemia due to strains only
      susceptible to colistin.

PMID- 16885057
TI  - Terminal deoxynucleotidyl transferase-positive cells in spleen, appendix and
      branchial cleft cysts in pediatric patients.
AB  - We evaluated spleens (n = 26), appendices (n = 10) and branchial cleft cysts (n =
      6) for TdT-positive cells in pediatric patients. In spleen, appendix and
      branchial cleft cysts the range of TdT-positivity was 0-13, 0-96 and 0-6 TdT+
      cells/hpf, respectively. In spleens, scattered TdT+ cells were seen most
      frequently in periarteriolar lymphoid sheath regions.

PMID- 16885058
TI  - Association of Hb Shelby with Hb S in the south of Brazil.
AB  - We, herein, report the first observation of compound heterozygosity for
      hemoglobin Shelby and hemoglobin S identified in the south of Brazil. The variant
      hemoglobin was identified by isoelectric focusing (IEF), high performance liquid
      chromatography (HPLC) and DNA sequence analysis.

PMID- 16885059
TI  - Evaluation of five staging systems in 470 patients with multiple myeloma.
AB  - We evaluated the prognostic significance of five staging systems in 470
      consecutive, previously untreated patients with multiple myeloma diagnosed
      between 1989 and 2006. The five staging systems were those proposed by Durie and
      Salmon, Bataille et al., the South West Oncology Group, Weber et al. and the
      International Staging System. This last proved to be superior to the others.

PMID- 16885060
TI  - Identification of a novel PROS1 c.1113T-->GG frameshift mutation in a family with
      mixed type I/type III protein S deficiency.
AB  - We report a family with type I and type III protein S (PS) deficiency, which
      showed to be phenotypic variants of the same genetic disease. Direct sequencing
      analysis of the PROS1 gene was performed to establish the genotype. The ratio of
      protein C antigen and total PS antigen levels (protein C/S ratio) was used to
      classify subjects at risk of venous thromboembolism. All PS deficient subjects
      had increased protein C/S ratios as well as a novel PROS1 c.1113T-->GG frameshift
      mutation.

PMID- 16885061
TI  - Impairment of endothelium-dependent aorta relaxation by phospholipid components
      of oxidized low-density lipoprotein.
AB  - Oxidized low-density lipoprotein (LDL) is a major component in the
      pathophysiology of atherosclerosis and plays a role in the changes of vascular
      reactivity observed in this disease. Herein the authors investigate the potential
      involvement of platelet-activating factor (PAF)-like phospholipid components of
      oxidized LDL in rabbit aorta reactivity. Aortic rings were precontracted with
      noradrenaline (0.5 microM) and relaxation was induced by subsequent stimulation
      with sequential additions of acetylcholine (1 nM to 3 microM). High-performance
      liquid chromatography (HPLC) fractions (6- and 7-min) obtained from phospholipids
      extracted from oxidized LDL inhibited relaxation evoked by acetylcholine, but not
      the relaxation induced by sodium nitroprusside. This effect was not antagonized
      either by incubation of the fractions with PAF acetylhydrolase or by incubation
      of the aortic rings with a PAF receptor antagonist. Authentic PAF or C4-PAF, a
      PAF mimetic previously found in fractions 6 and 7 did not inhibit acetylcholine
      induced relaxation. In contrast, lyso-PAF inhibited acetylcholine, but not sodium
      nitroprusside-induced relaxation. The authors conclude that phospholipids of
      oxidized LDL impair vascular reactivity to endothelium-dependent agonists. This
      effect is not due to oxidatively generated proinflammatory PAF mimetics, but
      rather to a metabolite of these phospholipids, lysoPAF.

PMID- 16885062
TI  - Distinct effects of high-glucose conditions on endothelial cells of macrovascular
      and microvascular origins.
AB  - Recent studies implicate hyperglycemia as an important cause of macrovascular and
      ocular complications in diabetes mellitus. In this study, the authors examined
      the effect of high glucose on macrovascular and microvascular endothelial cell
      viability and apoptosis in culture. Human aortic endothelial cells (HAECs) and
      human retinal endothelial cells (HRECs) were exposed to normal-glucose conditions
      (NG) and high-glucose conditions (NG supplemented with 25 mM D-glucose) for 72 h
      in vitro. D-Mannitol was used as an osmotic control. Cell viability was assessed
      by methlythiazolydiphenyltetrazolium bromide (MTT) assay, and induction of
      apoptosis was assessed by Hoechst staining. Statistics were analyzed by paired t
      tests. In HAECs, cell viability was decreased by 12.9% in high-glucose
      conditions, and apoptotic cells were significantly increased by 77%. However, in
      HRECs, cell viability was increased by 14.9% in high-glucose conditions, and
      apoptotic cells were significantly decreased by 33.3%. Mannitol did not show any
      effect on cell survival or apoptosis ruling out an osmotic effect. High-glucose
      conditions reduce cell viability and induce apoptosis in HAECs, which may
      contribute to macrovascular complications associated with diabetes. In contrast,
      high-glucose increases viability in HRECs and inhibits apoptosis, which may
      contribute to the development of diabetic retinopathy.

PMID- 16885064
TI  - Evaluation of the porcine ameroid constrictor model of myocardial ischemia for
      therapeutic angiogenesis studies.
AB  - The porcine ameroid model of chronic myocardial ischemia has been widely used for
      the evaluation of coronary collateralization development. The impact of target
      vessel occlusion on the presence of myocardial ischemia, and the relationship
      between morphological, functional, and hemodynamic measurements in the context of
      therapeutic angiogenesis studies, however, has not been studied thus far. The
      authors therefore performed a systematic analysis of 94 animals undergoing
      ameroid constrictor placement around the left circumflex coronary artery (LCX)
      and, furthermore, a comprehensive evaluation including echocardiography and
      coronary angiography 26 +/- 1 (mean +/- SEM) days after ameroid placement.
      Complete LCX occlusion was observed in 34/94 animals (36%) and identified those
      with myocardial ischemia of the lateral wall, both at rest and under
      pharmacological stress. By applying a set of angiographic criteria (TIMI <or= 2
      flow in LCX and/or collateral flow Rentrop class >or= 1), another 27/94 animals
      with myocardial ischemia under conditions of pharmacological stress conditions
      could be identified. Interestingly, echocardiographic parameters of regional and
      global myocardial function were not correlated with myocardial blood flow or the
      degree of ischemia. There was no relationship between the extent of coronary
      collateralization, as assessed by angiography, echocardiographic parameters, or
      myocardial blood flow. The authors therefore conclude that complete occlusion of
      the ameroid instrumented coronary artery is not a prerequisite for successfully
      establishing the pathophysiology of myocardial ischemia. Defined angiographic
      criteria are important in identifying ischemic animals, thus reducing total
      animal numbers. Angiographic assessment of the degree of coronary
      collateralization, however, is not associated with myocardial blood flow or
      function and should not be used as a primary outcome measure of therapeutic
      angiogenesis studies in this model.

PMID- 16885063
TI  - Dietary silica modifies the characteristics of endothelial dilation in rat aorta.
AB  - Considering the importance of nitric oxide generation in the regulation of vessel
      tone, reduced endothelial nitric oxide synthase (eNOS) expression in alveolar
      macrophages exposed to short-term silica (Si) suggests the possibility of Si
      induced changes in endothelial functions. In this experimental study, the
      functional changes of the endothelial cells were investigated in the aortic rings
      of rats subjected to 50 mg Si/kg body weight in their drinking water for 8 days.
      Norepinephrine elicited contractility and dilation response to acetylcholine
      (ACh) was significantly high in the aortic rings of Si-treated group. Alteration
      in receptor-independent endothelial response to A23187 in the aortic rings of Si
      exposed rats was less obvious, but sodium nitroprusside (SNP)-elicited dilation
      was reduced significantly. A23187-induced relaxation was fully eliminated with N
      nitro-L-arginine methyl ester (L-NAME) pretreatment, whereas 19.24 +/- 4.36% of
      ACh response was L-NAME resistant and eliminated with 10-5 M tetraethylammonium
      (TEA). Despite a significant reduction in the share of NO, the contribution of
      indomethacine (IND)-sensitive relaxation to ACh response remained unchanged in Si
      group. As a result, our findings demonstrated that Si both modifies the
      characteristics of endothelial relaxants and attenuates smooth muscle cell
      responsiveness to NO. Si-induced reduced NO association with elevated endothelium
      derived hyperpolarizing factor (EDHF) in response to ACh, together with reduced
      NO sensitization, might have clinical importance in cardiovascular pathology.

PMID- 16885065
TI  - An investigation into the effect of surface roughness of stainless steel on human
      umbilical vein endothelial cell gene expression.
AB  - The surface properties of vascular devices dictate the initial postimplantation
      reactions that occur and thus the efficacy of the implantation procedure. Over
      the last number of years, a number of different stent designs have emerged and
      stents are generally polished to a mirror finish during the manufacturing
      procedure. This study sought to investigate the effect of stainless steel surface
      roughness on endothelial cell gene expression using an appropriate cell culture
      in vitro assay system. Stainless steel discs were roughened by shot blasting or
      polished by mechanical polishing. The surface roughness of the treated and
      untreated discs was determined by atomic force microscopy (AFM). Cells were
      seeded on collagen type 1 gels and left to attach for 24 h. Stainless steel discs
      of varying roughness were then placed in contact with the cells and incubated for
      24 h. RNA extractions and quantitative real-time reverse transcriptase-polymerase
      chain reaction (RT-PCR) was then performed to determine the expression levels of
      candidate genes in the treated cells compared to suitable control cells. E
      selectin and vascular cellular adhesion molecule (VCAM-1) were found to be
      significantly up-regulated in cells incubated with polished and roughened
      samples, indicating endothelial cell activation and inflammation. This study
      indicates that the surface roughness of stainless steel is an important surface
      property in the development of vascular stents.

PMID- 16885066
TI  - p38 Mitogen-activated protein kinase activation in endothelial cell is implicated
      in cell alignment and elongation induced by fluid shear stress.
AB  - Fluid shear stress is thought to be important in maintaining the phenotype of
      endothelial cells (ECs) in vivo. The purpose of the study was to determine the
      effect of varying levels of laminar shear stress on EC elongation and alignment
      and the role of p38 mitogen-activated protein kinase (MAPK) on the morphologic
      change induced by shear stress. Cultured bovine aortic ECs were subjected to 1,
      4, 7, 14, or 20 dyne/cm(2) laminar steady shear stress. On morphometric analysis
      of static ECs, the average orientation angle was 41 degrees , whereas after 24 h
      shear stress at 1, 4, 7, 14, and 20 dyne/cm(2) the angles were 34 degrees, 33
      degrees, 16 degrees, 11 degrees, and 10 degrees, respectively. The shape index of
      static ECs was 0.76, whereas the indexes of ECs exposed to shear stress were
      0.72, 0.72, 0.65, 0.50, and 0.47, respectively. The time and the magnitude of
      activation of p38 MAPK were dependent on the level of shear stress. The results
      indicate that a minimum shear stress of 7 to 14 dynes/cm(2) is necessary for cell
      alignment and elongation and this correlates with activity of p38 MAPK. ECs
      exposed to shear stress in the presence of the p38 MAPK inhibitor SB-203580 did
      not orient in any manner and the shape index was similar to the static cells.

PMID- 16885069
TI  - Stent-based percutaneous coronary interventions in small coronary arteries.
AB  - A third to half of all percutaneous coronary interventions involve small diameter
      vessels of less than 3 mm. Small vessel size is a predictor of restenosis after
      balloon angioplasty, as well as after stent placement. Stents deployed in small
      arteries, have a higher metal-to-artery ratio; this may increase the risk of sub
      acute thrombosis or restenosis. Various studies have shown that stent design,
      stent coating, and stent strut thickness may determine event-free survival.
      Dedicated stents for small vessels with less amount of metal, appropriate
      expansion to the vessel size with correct radial force and cells morphology, and
      less prothrombotic properties, may further improve the results of stenting in
      this setting (thinner struts, fewer cells, or loops per circumference). This
      review provides an update on the current status, review the major trials and
      define the clinical utility of small vessel stenting, particularly in the era of
      drug-eluting stents.

PMID- 16885067
TI  - Nerve growth factor (NGF) promotes angiogenesis in the quail chorioallantoic
      membrane.
AB  - Angiogenesis, the formation of new blood vessels, is tightly regulated by growth
      factors, such as vascular endothelial growth factor (VEGF) and fibroblast growth
      factor (FGF). The authors hypothesize that nerve growth factor (NGF), a well
      known neurotrophin, may play a direct angiogenic role. To test this hypothesis,
      the authors measured the effects of NGF on the natural vascularization of the
      quail chorioallantoic membrane (CAM). The angiogenic effect of NGF was compared
      to that of human recombinant VEGF165 (rhVEGF) and basic FGF (rhbFGF). In
      comparison to phosphate-buffered saline-treated controls, NGFs from different
      biological sources (mouse, viper, and cobra) increased the rate of angiogenesis
      in a dose-dependent fashion from 0.5 to 5 microg. For quantitative morphometry,
      grayscale images of the blood vessels end points of the CAM arteries were
      binarized for visualization and skeletonized for quantization by fractal
      analysis. In mouse NGF-treated embryos the fractal dimension (Df), indicative of
      arterial vessel length and density, increased to 1.266 +/- 0.021 compared to
      1.131 +/- 0.018 (p < .001) for control embryos. This effect was similar to that
      of 0.5 microg rhVEGF (1.290 +/- 0.021, p < .001) and 1.5 microg rhbFGF (1.264 +/-
      0.028, p < .001). The mouse NGF-induced angiogenic effect was blocked by 1 microM
      K252a (1.149 +/- 0.018, p < .001), an antagonist of the NGF/trkA receptor, but
      not by 1 microM SU-5416 (1.263 +/- 0.029, p < .001), the VEGF/Flk1 receptor
      antagonist, indicating a direct, selective angiogenic effect of NGF via quail
      embryo trkA receptor activation. These results confirm previous observations that
      NGF has angiogenic activity and suggest that this neurotrophin may also play an
      important role in the cardiovascular system, besides its well-known effects in
      the nervous system. The angiogenic properties of NGF may be beneficial in
      engineering new blood vessels and for developing novel antiangiogenesis therapies
      for cancer.

PMID- 16885070
TI  - Effects of abciximab as adjunctive therapy in primary percutaneous coronary
      intervention patients (results from the DANAMI-2 trial).
AB  - INTRODUCTION: Successful reperfusion at the epicardial level is not always
      accompanied by reperfusion of the microvasculature. Therapies targeted against
      'no-flow' are often employed in patients receiving primary percutaneous coronary
      intervention (pPCI) after acute myocardial infarction. HYPOTHESIS: Abciximab as
      adjunctive to pPCI will improve ST-segment resolution used as a surrogate for
      optimal microvascular reperfusion, and improve prognosis. METHODS: In the DANAMI
      2 trial 309/790 (39%) patients treated with pPCI received abciximab at physician
      discretion. SigmaST-segment elevation at baseline, 90 min, 4 h, 12 h, 24 h after
      pPCI and at discharge was measured and ST-segment resolution grouped as: Complete
      (> or = 70 %); Partial (> or = 30 to < 70%); No (< 30%). Clinical endpoints were
      death, re-infarction and disabling stroke. RESULTS: Abciximab prescription varied
      from 24.4-60.3% in the different hospitals. Patients receiving abciximab had a
      higher risk profile. ST-segment resolution at 90 min and 24 h was identical in
      the two groups, but at 4 h and 12 h partial ST-segment resolution was more
      pronounced in patients receiving abciximab (P = 0.001, P = 0.026). In a
      multivariate analysis, adjusting for baseline differences abciximab was
      associated with improved partial ST-segment resolution at 12 h. Patients treated
      with abciximab had no re-infarction at 30 days (0% versus 2.8%, P = 0.003), but
      increased disabling stroke rate (2.3% versus 0.4%; P = 0.019) driven by cerebral
      infarctions, and not intracranial hemorrhage. There were no differences in death
      rates. CONCLUSIONS: In the DANAMI-2 trial with no age limit, the decreased re
      infarction rates in patients receiving abciximab was offset by increased
      disabling stroke rates. Abciximab in conjunction with pPCI is associated with
      more pronounced partial ST-segment resolution after 4 h to 12 h suggesting
      improved microvascular reperfusion.

PMID- 16885071
TI  - Rescue percutaneous coronary intervention after failed thrombolysis: results from
      the Acute Coronary Syndrome Israel Surveys (ACSIS).
AB  - BACKGROUND: The benefit of rescue percutaneous coronary intervention (PCI) in
      acute myocardial infarction patients, who fail to show signs of reperfusion after
      full dose thrombolysis, is still an unresolved issue. AIM: To assess the outcomes
      of patients who underwent rescue PCI after full-dose thrombolytic therapy and
      compare them to patients treated only with thrombolysis in the Acute Coronary
      Syndrome Israel Surveys (ACSIS). METHODS: ACSIS is a biannual survey on acute
      myocardial infarction performed in all 26 intensive cardiac care units in Israel
      during a two-month period. 2,018 patients were admitted with acute myocardial
      infarction during the two-month period in the 2000 and 2002 surveys, and 796 of
      them were treated with thrombolytic therapy. RESULTS: Rescue PCI was performed in
      99 patients who failed to show signs of reperfusion. The control group consisted
      of patients with unsuccessful thrombolysis and no further intervention. Patients
      who underwent rescue PCI had a numerically higher incidence of anterior wall
      myocardial infarction, diabetes, higher Killip class on admission and cardiogenic
      shock. Furthermore, almost half of these patients had reduced left ventricular
      function (P = 0.03). During hospitalization, there was a significantly higher
      prevalence of recurrent ischemic events and major bleeding complications in
      patients who underwent rescue PCI. In-hospital, 30-day and one-year mortality
      rates were similar between the two groups. By multivariate analyses, Killip class
      3-4 (OR: 2.62, CI = 0.95-6.58, P = 0.05) and streptokinase treatment (OR: 0.623,
      CI = 0.4-0.97, P = 0.05) were independent predictors of rescue PCI. Rescue
      angioplasty was associated with 15% risk-reduction (CI = 0.45-1.97, P = 0.05) in
      30-day mortality and recurrent emergent hospitalization. CONCLUSIONS: Patients
      who underwent rescue PCI had similar short- and long-term mortality rates
      compared to patients treated with thrombolysis alone, despite differences in
      baseline characteristics. Rescue angioplasty was associated with a 15% risk
      reduction in mortality at 30-days, at the cost of higher rate of recurrent
      ischemic events and bleeding complications. Therefore, rescue angioplasty may be
      an equalizer in severely ill patients who receive thrombolytic therapy and fail
      to show signs of reperfusion.

PMID- 16885072
TI  - The eccentric lumenology.
AB  - Coronary angiography has a poor predictive value for the detection of eccentric
      plaque morphology. Many reports have demonstrated discordance between the
      angiographic classification and the intravascular ultrasound (IVUS)
      classification. Although eccentricity is usually considered a dichotomous
      character, more than two-thirds of all coronary stenosis have some degree of
      eccentricity. The American College of Cardiology/American Heart Association
      (ACC/AHA) Task force included lesion eccentricity as a risk factor for moderate
      procedural success (60-85%) and moderate complications (type B). Although lesion
      eccentricity has been implicated as a risk factor for reduced short-term
      procedural results, current available data does not support the adverse impact of
      eccentricity on procedural success or restenosis. The present article reviews the
      incidence and the various clinical scenarios known to be associated with the
      eccentric lumenogram and the impact of coronary artery remodeling contributing to
      misinterpretation of disease eccentricity. Various therapeutic modalities with
      reference to eccentric lesions are also considered.

PMID- 16885073
TI  - Is increased body mass index associated with a cardioprotective effect after ST
      segment-elevation myocardial infarction?
AB  - Recent studies highlighted the 'obesity paradox' after revascularization,
      suggesting a 'cardioprotective' effect of obesity. We assessed the association of
      BMI and regional wall motion score (RWMS) and peak CK and cTnI values (markers of
      infarct size) and 30-day survival among consecutive first ST-segment-elevation
      myocardial infarction patients who underwent successful primary PCI. Of the 164
      patients, we found no difference in infarct size among the different groups, BMI
      < or = 25 kg/m2, 25 < BMI < or = 30 kg/m2, and BMI > 30 kg/m2, and no association
      between BMI as continuous variable and these variables. Thirty-day death rates
      were not statistically different among the three groups (10, 5, 2%, respectively,
      P = 0.83). Increased BMI does not confer any protective effect on the heart
      during acute ischemia.

PMID- 16885074
TI  - Contrast enhanced multi-detector computed tomography coronary angiography versus
      conventional invasive quantitative coronary angiography in acute coronary
      syndrome patients-correlation and bias.
AB  - BACKGROUND: Previous studies that compared multi-detector computed tomography
      (MDCT) non-invasive coronary angiography with conventional coronary angiography,
      did not assessed the ability of MDCT to detect stenotic lesions correctly in
      acute coronary syndromes (ACS) patients. The aim of the present study was to
      assess prospectively the correlation and bias between 16-slice MDCT coronary
      angiography and quantitative coronary angiography analysis (QCA) in these
      patients. METHODS: Patients underwent electrocardiogram-gated, 16-slice MDCT
      coronary angiography and routine invasive percutaneous coronary angiography with
      quantitative coronary angiography (QCA) analysis blinded to MDCT results. The
      correlation and the bias between the results of MDCT and QCA were assessed in
      segments observed by both modalities in vessels > or = 2 mm in diameter. RESULTS:
      59 patients (81% male, age 56 +/- 11 years), admitted due to ACS, underwent MDCT
      and invasive coronary angiography. 544 segments were analyzed. The correlations
      between MDCT and QCA observed for the left anterior descending coronary artery
      (LAD), the left circumflex coronary artery (Cx), the right coronary artery (RCA)
      and for all analyzed segments were 0.74 (P < 0.0001), 0.54 (P < 0.009), 0.72 (P <
      0.0001) and 0.70 (P < 0.0001), respectively. By Bland-Altman analysis, a small
      overestimation of the lesion severity with MDCT of 4.8% for the LAD, 5.9% for the
      Cx, and 3.3% for the RCA was observed. CONCLUSIONS: In ACS patients, MDCT
      contrast-enhanced coronary angiography provides good quantification of the
      luminal diameter as compared to coronary angiography, and it is characterized by
      a small overestimation bias.

PMID- 16885075
TI  - Quantification of multi-slice computed tomography coronary angiography: current
      status and future directions.

PMID- 16885076
TI  - Persistent angina pectoris in a 17-year-old patient.

PMID- 16885077
TI  - Large vegetation associated with implantable cardioverter-defibrillator lead.

PMID- 16885078
TI  - Ultrasound attenuation behind coronary atheroma without calcification: mechanism
      revealed by autopsy.
AB  - When performing intravascular ultrasound studies, the backward echo image can
      show marked attenuation, although there are no calcified deposits and it may be
      impossible to detect the intraplaque architecture. The pathology underlying this
      phenomenon was investigated in autopsy specimens. We hypothesize that the
      mechanism responsible for the attenuation involves micro-calcification and lipid
      in unstable plaques causing ultrasonic wave reflection and dispersion.

PMID- 16885079
TI  - Bilateral ostial coronary stenosis and rheumatic aortic valve stenosis.
AB  - A 49-year-old patient presented with angina pectoris and clinical findings of
      aortic valve stenosis and regurgitation. Rheumatic aortic valve stenosis and
      regurgitation was diagnosed on echocardiography. Coronary angiography findings
      showed severe calcification in the aorta root with right coronary ostial
      occlusion, and were suggestive of left main ostial stenosis and proximal main
      stem stenosis, which was confirmed on CT angiography. Curvilinear calcification
      of the aorta was present on CT angiography. The findings suggested syphilitic
      aortitis. Syphilis serology was positive (RPR titre 1/16). The angina was caused
      by severe coronary ostial disease likely due to syphilitic aortitis and
      exacerbated by the rheumatic aortic valve stenosis and regurgitation.

PMID- 16885080
TI  - Late acute thrombosis after implantation of sirolimus-eluting stent to treat in
      stent restenosis.
AB  - Drug-eluting stents (DES) have significantly reduced the incidence of in-stent
      restenosis (ISR) compared to bare metal stents (BMS). However, recent randomized
      trials comparing DES with BMS reported few cases of late DES thrombosis. We
      report the case of late sirolimus-eluting stent thrombosis occurring 22 months
      after its elective implantation in a restenotic BMS and soon after the
      interruption of combined anti-platelet therapy with aspirin and Clopidogrel.

PMID- 16885081
TI  - Unexpected result of percutaneous coronary intervention-two for the price of one.
AB  - Anomalous coronary arteries are uncommon. This case illustrates an unusual result
      of percutaneous coronary intervention to the right coronary artery (RCA), where
      the circulation was also restored in the left anterior descending artery (LAD)
      territory via an anomalous vessel.

PMID- 16885082
TI  - Postcardiac injury syndrome complicating radiofrequency ablation of the
      atrioventricular node.
AB  - Radiofrequency ablation, which is increasingly used in the treatment of cardiac
      arrhythmia, can be complicated with pericardial effusion and one case of
      Dressler's syndrome has already been reported after an atrioventricular pathway
      ablation. This case reports a second case complicating an atrioventricular node
      radiofrequency ablation procedure.

PMID- 16885083
TI  - Successful angioplasty of an occluded aberrant coronary artery: a rare cause of
      acute myocardial infarction.
AB  - A 48-year-old woman was admitted for an acute infero-lateral myocardial
      infarction (AMI). The coronary angiography showed an occluded aberrant left
      circumflex artery taking off from the right sinus of Valsalva of the aortic root.
      This rare coronary anomaly represents a challenge for interventional
      cardiologists, especially in the setting of AMI, since it may be difficult to
      identify an aberrant occluded vessel, to predict its origin and course and
      finally to choose the material which offers an adequate support during the
      revascularization procedure. In this particular case, the percutaneous treatment
      of initially occluded aberrant circumflex artery was performed successfully.

PMID- 16885084
TI  - The moral domain of the medical record: the routine ethics evaluation.
AB  - The structure, content, and orientation of the contemporary medical record
      inadequately reflect the appropriate influence of patients' rights and bioethics
      on health care. Most tellingly, the medical chart reveals a remarkable absence of
      attention to medical ethics, except in the case of crisis management. But medical
      ethics informs both crisis decision-making and virtually all clinical
      interventions. Indeed, clinical care embodies a complex array of choices
      influenced by individual and cultural values, themselves reflecting religious
      beliefs, personal histories, psychologies, and social mores. But the typical
      medical chart, which records clinical descriptions, analyses, and rationales for
      treatment, rarely identifies or accounts for this value-laden dimension of care
      and thus both over-simplifies and distorts the depiction of a patient's illness
      and its treatment. To better reflect the complex moral domain of clinical care,
      and assist in organizing its complex structure, a systematic procedure is
      proposed here to evaluate the ethical status of every patient: As a routine part
      of the clinical evaluation, in a designated Ethical Concerns section of the
      medical record, an "ethics work-up' is designed to serve as a moral 'diagnostic'
      analogous to its scientific counterpart. Adapted to the needs of individual
      patients, such evaluations should identify ethical problems, coordinate related
      data, resources, and opinion, and define the rationale for choices made and
      actions pursued. In establishing improved integration of the 'epistemologies' of
      care and the 'ethics' of care, the goals of a more humane, patient-centered
      medicine may be better met.

PMID- 16885085
TI  - Rethinking professional ethics in the cost-sharing era.
AB  - Changes in healthcare financing increasingly rely upon patient cost-sharing to
      control escalating healthcare expenditures. These changes raise new challenges
      for physicians that are different from those that arose either under managed care
      or traditional indemnity insurance. Historically, there have been two distinct
      bases for arguing that physicians should not consider costs in their clinical
      decisions--an "aspirational ethic" that exhorts physicians to treat all patients
      the same regardless of their ability to pay, and an "agency ethic" that calls on
      physicians to be trustworthy advisors to their patients. In the setting of
      greater patient cost-sharing, physicians' aspiration and agency roles
      increasingly conflict. Satisfactorily navigating the new terrain of consumer
      driven healthcare requires physicians to consider these two roles and how they
      can best be reconciled so as to maximize quality of care while respecting the
      heterogeneity of patients' financial resources and willingness to pay.

PMID- 16885086
TI  - Why we must leave our organs to others.
AB  - Organ procurement presents several ethical concerns (from what constitutes
      acceptable criteria for death to issues involved in specifically designating to
      whom an organ can be given), but none is more central than the concern for what
      are appropriate means for acquiring organs. The following discussion attempts a
      different perspective on the issue of organ procurement by arguing that, rather
      than appealing to our charitable consciences or our pocketbooks, relinquishing
      our organs after death in this day and age is, in fact, obligatory for most
      people. Each of us is pressed by the growing demand for our organs should we die
      "rightly," and that desperate need has risen to such a level that not to release
      our organs for transplantation would constitute a serious moral wrong.

PMID- 16885087
TI  - Ethics, biotechnology, and global health: the development of vaccines in
      transgenic plants.
AB  - As compared with conventional vaccine production systems, plant-made vaccines
      (PMVs) are said to enjoy a range of advantages including cost of production and
      ease of storage for distribution in developing countries. In this article, we
      introduce the science of PMV production, and address ethical issues associated
      with development and clinical testing of PMVs within three interrelated domains:
      PMVs as transgenic plants; PMVs as clinical research materials; and PMVs as
      agents of global health. We present three conclusions: first, while many of the
      ethical issues raised by PMVs are familiar, PMVs add a new dimension to old
      issues, and raise some novel issues for ethicists and policy-makers; secondly, it
      is premature to promise broad applicability of PMVs across the developing world
      without having demonstrated their feasibility; thirdly, in particular, proponents
      of PMVs as a solution to global health problems must, as a condition of the
      ethical conduct of their research, define the commercial feasibility of PMVs for
      distribution in the developing world.

PMID- 16885089
TI  - Response to commentaries on "is there a rural ethics literature?".

PMID- 16885090
TI  - Letter to the Editor: Emergency research consent waiver--a proper way.

PMID- 16885091
TI  - Evidence-based equipoise and research responsiveness.

PMID- 16885092
TI  - Routine screening: informed consent, stigma and the waning of HIV exceptionalism.
AB  - The Centers for Disease Control and Prevention (CDC) recently recommended that
      HIV screening should become routine for all adults in the United States. Implicit
      in the CDC proposal is the notion that pre-test counseling would be more limited
      than at present, and that written informed consent to screening would no longer
      be required. If widely implemented, routine testing would mark a tremendous shift
      in the US HIV screening strategy. There are a number of considerations used to
      determine what screening tests should be routine, and HIV fits the bill in almost
      every regard. Yet the stigma associated with HIV infection remains, making the
      CDC's recommendation highly controversial. Will minimizing requirements for pre
      test counseling and special written informed consent lead to unexpected or
      unwanted HIV testing, or do these stringent counseling and consent requirements
      needlessly scare people away? Will widespread and routine testing be associated
      with declining stigmatization, or will it drive some patients away from seeking
      desperately needed health care? These are high stakes questions, and we're about
      to find out the answers.

PMID- 16885093
TI  - Ethics and professionalism: what does a resident need to learn?
AB  - Training in ethics and professionalism is a fundamental component of residency
      education, yet there is little empirical information to guide curricula. The
      objective of this study is to describe empirically derived ethics objectives for
      ethics and professionalism training for multiple specialties. Study design is a
      thematic analysis of documents, semi-structured interviews, and focus groups
      conducted in a setting of an academic medical center, Veterans Administration,
      and community hospital training more than 1000 residents. Participants were 84
      informants in 13 specialties including residents, program directors, faculty,
      practicing physicians, and ethics committees. Thematic analysis identified
      commonalities across informants and specialties. Resident and nonresident
      informants identified consent, interprofessional relationships, family
      interactions, communication skills, and end-of-life care as essential components
      of training. Nonresidents also emphasized formal ethics instruction, resource
      allocation, and self-monitoring, whereas residents emphasized the learning
      environment and resident-attending interactions. Conclusions are that empirically
      derived learning needs for ethics and professionalism included many topics, such
      as informed consent and resource allocation, relevant for most specialties,
      providing opportunities for shared curricula and resources.

PMID- 16885094
TI  - Focusing on education rather than clinical ethics.

PMID- 16885095
TI  - Getting from here to there.

PMID- 16885096
TI  - Systematic review of ethics consultation: a route to curriculum development in
      post-graduate medical education.

PMID- 16885097
TI  - Residency education in clinical ethics and professionalism: not just what, but
      when, where, and how ought residents be taught?

PMID- 16885098
TI  - Ethics consultation as a tool for teaching residents.

PMID- 16885099
TI  - Education in professionalism should never end.

PMID- 16885100
TI  - An unexpected opening to teach the impact of interactions between healthcare
      personnel.

PMID- 16885101
TI  - What's legal? What's moral? What's the difference? A guide for teaching
      residents.

PMID- 16885102
TI  - Teaching residents to consider costs in medical decision making.

PMID- 16885103
TI  - Strategies for incorporating professional ethics education in graduate medical
      programs.

PMID- 16885104
TI  - The real problem with equipoise.
AB  - The equipoise requirement in clinical research demands that, if patients are to
      be randomly assigned to one of two interventions in a clinical trial, there must
      be genuine doubt about which is better. This reflects the traditional view that
      physicians must never knowingly compromise the care of their patients, even for
      the sake of future patients. Equipoise has proven to be deeply problematic,
      especially in the Third World. Some recent critics have argued against equipoise
      on the grounds that clinical research is fundamentally distinct from clinical
      care, and thus should be governed by different norms. I argue against this
      "difference position," and instead take issue with the traditional, exclusively
      patient-centered account of physicians' obligations that equipoise presupposes.
      In place of this traditional view, I propose a Kantian test for the reasonable
      partiality that physicians should show their patients, focusing on its
      application in clinical research and medical education.

PMID- 16885105
TI  - The moral foundations of equipoise and its role in international research.

PMID- 16885106
TI  - Are there three or four distinct types of medical practice?

PMID- 16885107
TI  - Clinical ethics versus clinical research.

PMID- 16885108
TI  - Why researchers cannot establish equipoise.

PMID- 16885109
TI  - Physicians as researchers: difficulties with the "similarity position".

PMID- 16885110
TI  - Equipoise and the ethics of clinical research revisited.

PMID- 16885111
TI  - Equipoise in the real world.

PMID- 16885112
TI  - Defending the distinction between research and medical care.

PMID- 16885113
TI  - What do I tell my patient?

PMID- 16885114
TI  - Extensions and refinements of the equipoise concept in international clinical
      research: would Benjamin Freedman approve?

PMID- 16885115
TI  - Role-differentiated morality: the need to consider institutions, not just
      individuals.

PMID- 16885116
TI  - The law of mass action.

PMID- 16885117
TI  - Splitting the difference position.

PMID- 16885120
TI  - Production of an extremly low dose procaterol HCl preparation by fluidized-bed
      coating method: in vitro and in vivo evaluation.
AB  - A convenient and reliable method to prepare procaterol HCl oral dosage form at an
      extremely low dosage (25 microg/cap) is presented in this paper. Procaterol HCl
      was mixed with the film-forming agent hydroxypropyl methylcellulose in an aqueous
      solution, which was then spray-coated on sugar spheres (Nu-pareil PG 20/25) to
      produce procaterol HCl pellets. The IR spectra of coated and noncoated pellets
      indicated that procaterol HCl was coated on the sugar spheres successfully with a
      weight increment less than 1%. Most of the coated pellets were able to pass
      through an 18-mesh screen with no agglomeration. The average weights of coated
      pellets filled inside of capsules were monitored during the filling process. A
      simple liquid chromatographic method was developed and validated for the assay
      and uniformity test of procaterol HCl in different dosage forms. The results of
      assay and content uniformity test for both in-house product and a commercial
      product, i.e., Meptin-mini tablet, were satisfied. The data of f(2) function and
      ANOVA analysis for the dissolution profiles of both procaterol HCl products
      suggested that they are pharmaceutical equivalent. In an in vivo study (n = 24),
      a single dose of 75 microg procaterol HCl was administrated to each volunteer and
      the plasma concentration of procaterol was determined by a LC/MS/MS method,
      developed by the same authors. There were no significant differences (p > 0.05)
      in the data of AUC(0-->16 h), AUC(0-->infinity), C(max), and MRT for both
      preparations. It is confirmed that the pellets capsule produced in this study is
      bioequivalent with Meptin-mini tablet.

PMID- 16885121
TI  - In vitro dissolution studies of sodium diclofenac granules coated with Eudragit L
      30D-55 by fluidized-bed system.
AB  - The objective of this work was to study the dissolution process of sodium
      diclofenac granules coated with a polymeric suspension of Eudragit L-30D-55 by
      fluidized bed. Methacrylic acid-methylmetacrylate copolymer, also known as
      Eudragit, has been used as a pH sensitive coating material to protect drug
      substances prior to delivery to the human intestines. The sodium diclofenac
      granules were prepared by wet granulation technology using microcrystalline
      cellulose (MICROCEL), sodium diclofenac, and polivinilpirrolidone K-30. The
      granules coating operation was carried out in a fluidized bed with top spraying
      by a double-fluid nozzle. The dissolutions studies of the coated granules were
      performed in triplicate in a dissolution test station according to USP XXIII
      (1995) "in vitro testing requirements" Method A (paddle method, rotation of 100
      RPM and temperature fixed at 37 degrees C). The dissolution mediums were 0.1N HCl
      solution and a pH 6.8 phosphate buffer solution, following the pH change
      dissolution procedure specified in USP for enteric-coated articles: 2 h of
      exposure to 750 mL of 0.1N HCl followed by testing in 1000 mL of pH 6.8 phosphate
      buffer, the pH being adjusted with 250 mL of 0.2 M tribasic sodium phosphate
      solution. The released amount of sodium diclofenac was periodically determined by
      UV spectrophotometry at wavelength of 276 nm, using a spectrophotometer UV-VIS HP
      8453. The coated product showed gastric resistance properties confirming the
      feasibility of the fluidized bed for applying enteric coating in granules and
      pharmaceutical powders.

PMID- 16885122
TI  - High-throughput evaluation of non-swellable controlled release matrix tablets.
AB  - Drug release from controlled-release (CR) matrix tablets involves the permeation
      and diffusion of water through the system. In this study, a new methodology is
      proposed for the measurement of water permeation and simultaneous drug release
      from the inert, non-swellable CR matrix tablet of diltiazem (DLT) and a
      correlation is made between these two processes. Cylindrical matrices were
      readily prepared by direct compression of pellets obtained by extrusion
      spheronization. Water transport was studied using tritiated water (HTO) as a
      permeant in a Franz-diffusion cell and simultaneously drug release was measured.
      Further, dissolution was performed on USP XXI/XXII dissolution apparatus I using
      demineralized water. Matrices showed a steady water-uptake up to 6 h and the
      steady state for HTO permeation lasting from 6-h to 24-h Flux of water permeated
      and flux of drug released correlated well. Thus, HTO permeation through the
      matrix tablet and the proposed methodology can be used as a tool and/or surrogate
      marker for evaluation of controlled release matrix tablets. This methodology can
      be coined as "high-throughput" in terms of amount of labor and resources required
      in comparison to that of dissolution.

PMID- 16885123
TI  - Formulation and evaluation of insulin dry powder for inhalation.
AB  - PURPOSE: Dry powder formulation of insulin for pulmonary administration was
      prepared to obtain increased drug deposition in the alveolar absorptive region.
      The deposition was studied by investigating the dispersion and deaggregation of
      insulin from the carrier lactose using an Andersen cascade impactor and twin
      stage impinger. The subsequent absorption following the deposition was studied by
      in vivo method. METHODS: Insulin in solution with absorption promoters was
      lyophilized. The powder was incorporated with lactose of different grades and
      their combinations as carriers to deliver using an inhaler device. Solid-state
      characteristics of the carrier as well as the drug powder were assessed by
      particle size and distribution measurement. The flow properties such as moisture
      content, powder density, angle of repose, and carr's compressibility index of the
      powder mixture were determined. The aerosol behavior of the powder was studied by
      dispersion using rotahaler(c) connected to a twin-stage impinger (TSI) and an
      eight-stage Andersen cascade impactor (ACI) operating at different flow rates of
      30-90 l/min. The in vivo performance was studied by deliverance to the
      respiratory tract of guinea pigs. The intratracheal bioavailability with
      respective to intravenous route was calculated by measuring the blood glucose
      reduction. RESULTS: The coarser particles of lactose in fractions of carrier
      containing a wide particle size distribution impacted in the preseperator of
      cascade impactor, and only the particle less than 10 microm size entered stage 0
      stage 7. Formulation containing 1:1 mixture of Respitose ML006 (62%<50 microm)
      and Respitose ML003 (37.8%<50 microm) as carrier imparts well deaggregation of
      insulin, and higher deposition leads to 52.3% of fine particle fraction at 60
      Lit/min and in vivo bioavailability of 82%. CONCLUSIONS: Insulin formulations
      containing 1:1 mixture of Respitose ML006 and Respitose ML003 as carrier can
      impart deeper deposition of drug particles and cause higher bioavailability. This
      suggests that carrier used in the formulation influenced the amount of insulin
      deposition in the alveolar region of the lung. Hence, it was concluded that the
      availability of insulin for systemic absorption depends on the particle size of
      the drug as well as the carrier lactose.

PMID- 16885124
TI  - Preformulation studies on imexon.
AB  - Imexon is an aziridine containing iminopyrrolidone that, through aziridine ring
      opening, is able to induce oxidative stress resulting in apoptosis. The main
      objective of this research was to conduct extensive preformulation studies on
      Imexon in order to understand the factors that affect its stability. The results
      obtained indicate that the stability of Imexon is dependent on pH, ionic
      strength, temperature, buffer species, and initial concentration. Degradation of
      Imexon follows apparent first-order degradation kinetics with the primary
      degradation product resulting from opening of the aziridine ring. In order to
      maximize stability, ionic strength, temperature, and initial concentration should
      be minimized, with an optimal range pH between 7.2 and 9.0. Experimentation with
      other aqueous solutions indicates that Imexon has increased stability in D5W as
      opposed to normal saline, while it undergoes rapid degradation in 6% H(2)O(2).
      Imexon is not ionizable between pH 5.0 to 8.5 and has an aqueous solubility of
      approximately 25 mg/mL over this range. Solid-state characterization has
      concluded that Imexon is a crystalline solid that begins decomposition at 165
      degrees C, prior to melting.

PMID- 16885125
TI  - Pegylated protein encapsulated multivesicular liposomes: a novel approach for
      sustained release of interferon alpha.
AB  - Hepatitis C viral chemotherapy suffers from a relatively short half-life of the
      interferon alpha-2a (IFN alpha). To address this issue, we investigated the
      effects of polyethylene glycol modification and their subsequent encapsulation in
      multivesicular liposomes (MVLs), on the release properties of IFN alpha. In the
      present study, interferon-alpha was conjugated with methoxy-polyethylene glycol
      (mPEG, MW 5000). Prepared IFN alpha-mPEG5000 conjugate (IFN alpha-mPEG5000) was
      purified with size exclusion chromatography. The relative in vitro anti-viral
      activity of pegylated interferon alpha-2a was found to 87.9% of the unmodified
      IFN alpha. Pegylated IFN alpha encapsulated multivesicular liposomes were
      prepared by double emulsification technique followed by evaporation of organic
      solvents from chloroform ether spherules suspended in water. Prepared MVLs were
      then characterized for shape, size, vesicle count, encapsulation efficiency, and
      in vitro release rate. In process stability studies of pegylated IFN alpha
      protein exhibited better stability when exposed to chloroform: diethyl ether (1:1
      ratio) mixture as well as variable vortexing time as compared to native IFN
      alpha. Relatively high percentage of encapsulation of protein ( approximately
      75%) was achieved. In vitro release profile of pegylated IFN alpha-mPEG5000
      containing MVLs in the PBS showed lower initial burst release with sustained and
      incomplete release over a period of 1 week. In contrast, native IFN alpha
      entrapped MVLs were observed as higher initial burst release, i.e., nearly 35%
      followed by almost complete release. The results confirmed the possibility of
      multivesicular liposomes as a long-acting or sustained-release delivery system
      using a combination of pegylation and encapsulation technique for controlled
      delivery of interferon alpha.

PMID- 16885126
TI  - Controlled release by permeability alteration of cationic ammonio methacrylate
      copolymers using ionic interactions.
AB  - A multiparticulate drug delivery system was studied in which the drug release of
      a model drug theophylline could be modulated by interactions of ammonio
      methacrylate polymer and anions. The system consisted of a EUDRAGIT NE coated
      anionic core, layered with drug and further layered with EUDRAGIT RS. The effects
      of different anions like chloride, succinate, citrate, and acetate as well as the
      thickness of the polymer layers on the in vitro drug release were studied. It was
      seen that succinate and acetate anions had permeability enhancing effects and
      citrate and chloride anions had permeability retarding effects on the polymer.
      The results indicate that changing these variables would enable us to get a
      desired release profile and hence the proposed system could be a viable
      alternative to existing technologies for the development of a controlled drug
      delivery system.

PMID- 16885127
TI  - Effect of phospholipid composition on characterization of liposomes containing 9
      nitrocamptothecin.
AB  - 9-Nitrocamptothecin (9-NC), a newly developed camptothecin derivative, had poor
      solubility in any pharmaceutically acceptable solvents. One way of improving the
      solubility is to formulate the drug into liposomes. However, 9-NC has low
      affinity to lipid membranes resulting in a very low drug-to-liposome entrapment.
      We developed a novel liposome-based 9-NC formulation which was composed of
      soybean phosphatidylcholine (SPC), hydrogenated soybean phosphatidylcholine
      (HSPC), and cholesterol. Compared with conventional liposomes composed of only
      SPC and cholesterol, 9-NC/lipid molar ratio increased from 1:72 to 1:18 while
      incorporation efficiency was still maintained about 80%. In addition, after 9-NC
      was encapsulated into novel liposomes, pharmacokinetic results revealed an
      increase in area under the plasma concentration-time curve (AUC) and a decrease
      in distribution volume of 9-NC following intravenous administration to rats.
      Increased stability in plasma may account for the improved pharmacokinetic
      behavior of the novel liposomes. Effect of HSPC/SPC molar ratio on
      characterization of the novel liposomes was also investigated. Except for
      drug/lipid molar ratio and encapsulation efficiency, HSPC/SPC molar ratio had
      only a little effect on other properties of novel liposomes. In conclusion, the
      study suggests that the novel liposomes can act as promising carriers for
      hydrophobic substances such as 9-NC.

PMID- 16885128
TI  - Development and preliminary experience with an ease of extractability rating
      system for prescription opioids.
AB  - One important factor in the abuse potential of an opioid product is the ease with
      which active drug can be extracted. There are currently no standards for testing
      or reporting extractability. This article describes the development of an
      Extractability Rating System for use by the pharmaceutical industry and
      regulators. Despite several limitations, this effort serves as a call for
      standardized testing and reporting so that products can be accurately rated, and
      should help establish goals for drug developers who wish to develop "abuse
      resistant" opioid products.

PMID- 16885129
TI  - Factors affecting stability of z-ligustilide in the volatile oil of radix
      angelicae sinensis and ligusticum chuanxiong and its stability prediction.
AB  - The purpose of this investigation is to obtain a suitable vehicle for Z
      ligustilide in the volatile oil of Radix Angelicae Sinensis and Ligusticum
      Chuanxiong in which it is stable enough for the application in pharmaceutics, to
      investigate its degradation laws, and to predict its shelf-life at 25 degrees C.
      Factors including temperature, light, pH value, co-solvents and antioxidants can
      all influence the stability of Z-ligustilide, thereinto antioxidants could
      markedly improve its stability in aqueous solution by almost 35%. The suitable
      vehicle for Z-ligustilide contains 1.5% tween-80, 0.3% Vitamin C, and 20%
      propylene glycol (PG). Furthermore, the degradation rates of Z-ligustilide were
      found to conform to a rate equation following Weibull probability distribution
      within a range of degradation ratio, and the equation could be expressed as
      follow: ln ln (1/1-alpha) = ln k + m ln t. Where alpha is degradation ratio; t is
      time; m and k are constants relating to the degradation rate. The degradation
      rate will get greater as the increasing of parameter k. According to the
      degradation law obtained from the equation, the drug shelf-life (10% of active
      ingredient degraded, T90) in this vehicle was predicted to be more than 1.77
      years at 25 degrees C through Arrehenius equation and accelerating experiments.
      The present investigation was undertaken to propose a kinetic treatment that may
      be applicable to any type of degradation of the active ingredient of
      pharmaceutical formulation, and also could provide a good foundation for the new
      drug development of Z-ligustilide, especially for injection formulation.

PMID- 16885130
TI  - Degradation kinetics of fluorouracil-acetic-acid-dextran conjugate in aqueous
      solution.
AB  - The degradation kinetics of fluorouracil-acetic-acid-dextran conjugate (FUAC
      dextran) was investigated in various buffer solutions with different pH value and
      physiological saline solution at 60 degrees C and 37 degrees C, respectively. The
      hydrolytic reaction displayed pseudo-first-order degradation kinetics. Hydrolytic
      rate constant obtained was the function of pH value and independent of species of
      buffering agents. The smallest rate constant was observed at pH round 3.00. The
      activation energy of the hydrolytic reaction was estimated from Arrhenius
      equation as 88.73 +/- 6.00 kJ.mol-1. The special base catalytic degradation of
      the conjugate was observed from acidic to slight alkaline condition and the
      special base catalytic rate constants were calculated. The conjugate was more
      stable in physiological saline than that in buffer solution at pH 7.00 or 9.00 at
      37 degrees C. The results revealed that the conjugate was stable in acidic
      condition and will degrade in alkaline condition.

PMID- 16885132
TI  - Does p-glycoprotein play a role in gastrointestinal absorption and cellular
      transport of dietary cholesterol?
AB  - This commentary discusses the potential role of p-glycoprotein (Pgp) on the
      gastrointestinal absorption and cellular transport of dietary cholesterol. This
      is currently a controversial issue due to the conflicting evidence about the role
      of this ABC transporter in cholesterol transport. During the preparation of this
      commentary, several key publications on this topic arguing for and against this
      mechanism have been published. If true, this mechanism of Pgp could represent a
      novel role for Pgp and provide a potentially new molecular target for drug design
      and development.

PMID- 16885131
TI  - The stability of insulin in solid formulations containing melezitose and starch.
      Effects of processing and excipients.
AB  - Solid insulin formulations obtained by different methods of preparation were
      compared with respect to chemical stability and morphology. Spray- and freeze
      drying, solution enhanced dispersion by supercritical fluids (SEDS) and
      precipitation into starch microspheres were the methods used for preparation of
      solid powders. The excipients applied were melezitose, starch, and sodium
      taurocholate. The stability of the samples was evaluated after storage in open
      containers at 25 degrees C and 30% RH for 6 months. All samples were amorphous
      after processing and storage as detected by XRD, except for the starch
      microspheres which were semi-crystalline. The spray- and freeze-dried samples
      containing melezitose and sodium taurocholate experienced a significant water
      uptake during storage, resulting in changes in morphology and disappearance of
      Tg. However, the chemical stability of these samples did not seem to be affected
      by the water uptake. Changes in morphology were not observed for the SEDS powders
      and the starch microspheres. The chemical stability of the samples was assessed
      by HPLC. In general, conventional spray- and freeze drying resulted in samples
      with higher chemical stability compared to SEDS powders and starch microspheres.
      Nevertheless, the excipients applied were observed to be of major importance, and
      further optimization of the formulation as well as processing conditions may lead
      to slightly different conclusions.

PMID- 16885137
TI  - What do we know about psycholinguistic effects?
AB  - Identifying clear and unequivocal psycholinguistic effects for lexical retrieval
      tasks has been the aim of a significant proportion of recent research activity.
      Debates have erupted concerning the existence or otherwise of particular effects
      on particular lexical tasks. Here, it is suggested that the reason for these
      debates is that researchers exercise choice in what variables they consider in
      their analysis. It is further illustrated that methods that have been employed
      for comparing the size of these effects between tasks can only lead to
      inconclusive results. It is suggested that psycholinguistic data may be better
      analysed using structural equation modelling methodologies. An example of such an
      approach is presented.

PMID- 16885138
TI  - The impact of letter detection on eye movement patterns during reading:
      Reconsidering lexical analysis in connected text as a function of task.
AB  - A comparison was made between reading tasks performed with and without the
      additional requirement of detecting target letters. At issue was whether eye
      movement measures are affected by the additional requirement of detection. Global
      comparisons showed robust effects of task type with longer fixations and fewer
      word skippings when letter detection was required. Detailed analyses of target
      words, however, further showed that reading with and without letter detection
      yielded virtually identical effects of word class and text predictability for
      word-skipping rate and similar effects for different word viewing duration
      measures. The overall oculomotor pattern suggested that detection does not
      substantially shift normal reading movements in response to lexical cues and
      thereby indicated that detection tasks are informative about word and
      specifically word class processing in normal reading.

PMID- 16885139
TI  - Reducing the own-race bias in face recognition by shifting attention.
AB  - The own-race bias (ORB) in face recognition can be interpreted as a failure to
      generalize expert perceptual encoding developed for own-race faces to other-race
      faces. Further, black participants appear to use different features to describe
      faces from those used by white participants (Shepherd & Deregowski, 1981). An
      experiment is reported where the size of the ORB was assessed using a standard
      face recognition procedure. Four groups were tested at two time intervals. One
      group received a training regime involving learning to distinguish faces that
      varied only on their chin, cheeks, nose, and mouth. Three control groups did not
      receive this training. The ORB, present prior to training, was reduced after the
      critical perceptual training. It is concluded that the ORB is a consequence of a
      failure of attention being directed to those features of other race faces that
      are useful for identification.

PMID- 16885140
TI  - A context-specific latent inhibition effect in a human conditioned suppression
      task.
AB  - Three studies used a computer video game preparation to demonstrate latent
      inhibition in adult humans. In all studies participants fired torpedoes at a
      target spaceship by clicking the mouse. Conditioned stimuli (CSs) were presented
      in the form of coloured "sensors" at the bottom of the screen. Conditioning was
      conducted by pairing a sensor with an attack from the target spaceship.
      Participants learned to suppress their rate of mouse clicking in preparation for
      an attack. In Experiment 1 a total of 10 preexposures to the sensor CS, prior to
      conditioning, retarded acquisition of suppression. In Experiment 2 the effect of
      preexposure was shown to be context specific. Experiment 3 showed little
      generalization of the preexposure effect from one sensor CS to another.
      Experiment 3 also showed that preexposure did not make the sensor CS inhibitory.
      Comparisons with conditioned suppression procedures with animals and negative
      priming procedures are briefly discussed.

PMID- 16885141
TI  - Orthogonal stimulus-response compatibility effects emerge even when the stimulus
      position is task irrelevant.
AB  - The above-right/below-left mapping advantage with vertical stimuli and horizontal
      responses is known as the orthogonal stimulus-response compatibility (SRC)
      effect. We investigated whether the orthogonal SRC effect emerges with irrelevant
      stimulus dimensions. In Experiment 1, participants responded with a right or left
      key press to the colour of the stimulus presented above or below the fixation. We
      observed an above-right/below-left advantage (orthogonal Simon effect). In
      Experiment 2, we manipulated the polarity in the response dimension by varying
      the horizontal location of the response set. The orthogonal Simon effect
      decreased and even reversed as the left response code became more positive. This
      result provides evidence for the automatic activation of the positive and
      negative response codes by the corresponding positive and negative stimulus
      codes. These findings extended the orthogonal SRC effect based on coding
      asymmetry to an irrelevant stimulus dimension.

PMID- 16885142
TI  - Exogenous influences on task set activation in task switching.
AB  - To explore the effect of exogenous processes on cognitive control, we used a
      cueing task-switching paradigm with two spatial judgement tasks and added an
      irrelevant colour attribute to the task-relevant spatial attribute of the target.
      The colour was not related to any specific Stimulus-Response relation in the
      tasks. A correlation was created between stimulus colour and task identity. This
      correlation was strong but imperfect in Experiment 1 and perfect in Experiment 2.
      As a result of the colour-task correlation, stimuli contained redundant
      information about task identity. By changing the correlation pattern every few
      blocks we caused this information to be sometimes invalid. In both experiments,
      performance was worse when the information carried by the target was invalid than
      when it was valid. However, this effect was exclusive to conditions with short
      task preparation time. By comparing performance with a control group, which had
      no colour-task correlation (in Experiment 2) we established that the colour
      manipulation did not cause a qualitative change in preparation strategy, and that
      the exogenous effect was stronger in switch trials than in repetition trials. We
      conclude that exogenous processes that are related to task set affect performance
      primarily if they are presented before endogenous processes of task set
      preparation have been launched.

PMID- 16885143
TI  - Reasoning about the relations between relations.
AB  - Relations can hold between relations, as in assertions such as: Cordelia loves
      Lear more than Goneril does. Naive reasoners can make inferences that depend on
      these higher order relations, which are vital for science and mathematics, but no
      existing theory explains such inferences. The present paper presents a theory
      based on mental models of the situations under description, and it reports four
      experiments corroborating the theory. Experiment 1a showed that the difficulty of
      such inferences from two premises depends on the integration of the information
      from the premises into a single model. The same result held in Experiment 1b,
      even when individuals were not permitted to make written workings. Experiment 2
      required the participants to think aloud, and their protocols revealed that they
      developed three main strategies. Experiment 3 biased the development of these
      strategies, showing that individuals assemble them "bottom up" from various
      tactical steps.

PMID- 16885144
TI  - Automatic-heuristic and executive-analytic processing during reasoning:
      Chronometric and dual-task considerations.
AB  - Human reasoning has been shown to overly rely on intuitive, heuristic processing
      instead of a more demanding analytic inference process. Four experiments tested
      the central claim of current dual-process theories that analytic operations
      involve time-consuming executive processing whereas the heuristic system would
      operate automatically. Participants solved conjunction fallacy problems and
      indicative and deontic selection tasks. Experiment 1 established that making
      correct analytic inferences demanded more processing time than did making
      heuristic inferences. Experiment 2 showed that burdening the executive resources
      with an attention-demanding secondary task decreased correct, analytic responding
      and boosted the rate of conjunction fallacies and indicative matching card
      selections. Results were replicated in Experiments 3 and 4 with a different
      secondary-task procedure. Involvement of executive resources for the deontic
      selection task was less clear. Findings validate basic processing assumptions of
      the dual-process framework and complete the correlational research programme of
      K. E. Stanovich and R. F. West (2000).

PMID- 16885145
TI  - Multiple-target tracking: A role for working memory?
AB  - In order to identify the cognitive processes associated with target tracking, a
      dual-task experiment was carried out in which participants undertook a dynamic
      multiple-object tracking task first alone and then again, concurrently with one
      of several secondary tasks, in order to investigate the cognitive processes
      involved. The research suggests that after designated targets within the visual
      field have attracted preattentive indexes that point to their locations in space,
      conscious processes, vulnerable to secondary visual and spatial task
      interference, form deliberate strategies beneficial to the tracking task, before
      tracking commences. Target tracking itself is realized by central executive
      processes, which are sensitive to any other cognitive demands. The findings are
      discussed in the context of integrating dynamic spatial cognition within a
      working memory framework.

PMID- 16885146
TI  - Lateralized repetition priming for familiar faces: Evidence for asymmetric
      interhemispheric cooperation.
AB  - Repetition priming refers to facilitated recognition of stimuli that have been
      seen previously. Although a great deal of work has examined the properties of
      repetition priming for familiar faces, little has examined the neuroanatomical
      basis of the effect. Two experiments are presented in this paper that combine the
      repetition priming paradigm with a divided visual field methodology to examine
      lateralized recognition of familiar faces. In the first experiment participants
      were presented with prime faces unilaterally to each visual field and target
      faces foveally. A significant priming effect was found for prime faces presented
      to the right hemisphere, but not for prime faces presented to the left
      hemisphere. In Experiment 2, prime and target faces were presented unilaterally,
      either to the same visual field or to the opposite visual field (i.e., either
      within hemisphere or across hemispheres). A significant priming effect was found
      for the within right hemisphere condition, but not for the within left hemisphere
      condition, replicating the findings of the first experiment. Priming was also
      found in both of the across hemispheres conditions, suggesting that
      interhemispheric cooperation occurs to aid recognition. Taken in combination
      these experiments provide two main findings. First, an asymmetric repetition
      priming effect was found, possibly as a result of asymmetric levels of activation
      following recognition of a prime face, with greater priming occurring within the
      right hemisphere. Second, there is evidence for asymmetric interhemispheric
      cooperation with transfer of information from the right hemisphere to the left
      hemisphere to facilitate recognition.

PMID- 16885147
TI  - Will Julia Roberts harm Nicole Kidman? Semantic priming effects during face
      naming.
AB  - Three experiments are reported, which examine whether face naming is vulnerable
      to semantic competition in a similar way to object naming. Previous experiments
      with object naming have shown that a related prime picture presented 3 trials
      before a target picture results in an increase in error rate and naming latencies
      when compared to unrelated prime conditions. The experiments here use the same
      paradigm, with errors as the main dependent variable. In Experiment 1, the prime
      and target faces were from the same occupational category (e.g., politicians,
      actors), and in Experiment 2, the primes and target faces were also associated to
      each other. In Experiment 3, the prime was presented as a name to be read aloud.
      Unrelated filler stimuli intervened between prime and target. In all experiments,
      there was a reduction in target-naming errors in the related conditions, and in
      Experiment 3 this was shown to be largely a reduction in naming failures. The
      results suggest that related name representations for famous people are not
      activated in parallel and in competition, and that there is some evidence for a
      relatively long lasting facilitatory effect. These results require some
      modification to any serial account of face naming to differentiate it from the
      generally well-established serial account of object naming.

PMID- 16885148
TI  - Role of insulin, adipocyte hormones, and nutrient-sensing pathways in regulating
      fuel metabolism and energy homeostasis: a nutritional perspective of diabetes,
      obesity, and cancer.
AB  - Traditionally, nutrients such as glucose and amino acids have been viewed as
      substrates for the generation of high-energy molecules and as precursors for the
      biosynthesis of macromolecules. However, it is now apparent that nutrients also
      function as signaling molecules in functionally diverse signal transduction
      pathways. Glucose and amino acids trigger signaling cascades that regulate
      various aspects of fuel and energy metabolism and control the growth,
      proliferation, and survival of cells. Here, we provide a functional and
      regulatory overview of three well-established nutrient signaling pathways-the
      hexosamine signaling pathway, the mTOR (mammalian target of rapamycin) signaling
      pathway, and the adenosine monophosphate-activated protein kinase (AMPK)
      signaling pathway. Nutrient signaling pathways are interconnected, coupled to
      insulin signaling, and linked to the release of metabolic hormones from adipose
      tissue. Thus, nutrient signaling pathways do not function in isolation. Rather,
      they appear to serve as components of a larger "metabolic regulatory network"
      that controls fuel and energy metabolism (at the cell, tissue, and whole-body
      levels) and links nutrient availability with cell growth and proliferation.
      Understanding the diverse roles of nutrients and delineating nutrient signaling
      pathways should facilitate drug discovery research and the search for novel
      therapeutic compounds to prevent and treat various human diseases such as
      diabetes, obesity, and cancer.

PMID- 16885149
TI  - Expression and actions of HIF prolyl-4-hydroxylase in the rat kidneys.
AB  - Hypoxia inducible factor (HIF) prolyl-4-hydroxylase domain-containing proteins
      (PHDs) promote the degradation of HIF-1alpha. Because HIF-1alpha is highly
      expressed in the renal medulla and HIF-1alpha-targeted genes such as nitric oxide
      synthase, cyclooxygenase, and heme oxygenase are important in the regulation of
      renal medullary function, we hypothesized that PHD regulates HIF-1alpha levels in
      the renal medulla and, thereby, participates in the control of renal Na(+)
      excretion. Using real-time RT-PCR, Western blot, and immunohistochemical
      analyses, we have demonstrated that all three isoforms of PHD, PHD1, PHD2, and
      PHD3, are expressed in the kidneys and that PHD2 is the most abundant isoform.
      Regionally, all PHDs exhibited much higher levels in renal medulla than cortex. A
      furosemide-induced increase in renal medullary tissue Po(2) significantly
      decreased PHD levels in renal medulla, whereas hypoxia significantly increased
      mRNA levels of PHDs in cultured renal medullary interstitial cells, indicating
      that O(2) regulates PHDs. Functionally, the PHD inhibitor l-mimosine (l-Mim, 50
      mg x kg(-1) x day(-1) i.p. for 2 wk) substantially upregulated HIF-1alpha
      expression in the kidneys, especially in the renal medulla, and remarkably
      enhanced (by >80%) the natriuretic response to renal perfusion pressure in
      Sprague-Dawley rats. Inhibition of HIF transcriptional activity by renal
      medullary transfection of HIF-1alpha decoy oligodeoxynucleotides attenuated l-Mim
      induced enhancement of pressure natriuresis, which confirmed that HIF-1alpha
      mediated the effect of l-Mim. These results indicate that highly expressed PHDs
      in the renal medulla make an important contribution to the control of renal Na(+)
      excretion through regulation of HIF-1alpha and its targeted genes.

PMID- 16885150
TI  - Toll-like receptor (TLR4) shedding and depletion: acute proximal tubular cell
      responses to hypoxic and toxic injury.
AB  - Acute renal failure (ARF) induces tubular hyperresponsiveness to TLR4 ligands,
      culminating in exaggerated renal cytokine/chemokine production. However, the fate
      of TLR4 protein during acute tubular injury remains unknown. The study sought new
      insights into this issue. Male CD-1 mice were subjected to 1) unilateral ischemia
      reperfusion (I/R), 2) cisplatin (CP) nephrotoxicity, or 3) glycerol-induced
      myohemoglobinuric ARF. Renal cortical TLR4 protein (Western blotting,
      immunohistochemistry) and TLR4 mRNA levels (RT-PCR) were determined thereafter
      (90 min-4 days). Urinary TLR4 excretion post-I/R or CP injection was also
      assessed. To gain proximal tubule-specific results, TLR4 protein and mRNA were
      quantified in posthypoxic or oxidant (Fe)-challenged isolated mouse tubules.
      Finally, TLR4 mRNA was determined in antimycin A-injured cultured proximal
      tubular (HK-2) cells. Acute in vivo renal injury reduced proximal tubule TLR4
      content. These changes corresponded with the appearance of TLR4 fragment(s) in
      urine and a persistent increase in renal cortical TLR4 mRNA. Isolated proximal
      tubules responded to injury with rapid TLR4 reductions, dramatic extracellular
      TLR4 release, and increases in TLR4 mRNA. Glycine blocked these processes,
      implying membrane pore formation was involved. HK-2 cell injury increased TLR4
      mRNA, but not protein levels, suggesting intact transcriptional, but not
      translational, pathways. Diverse forms of acute tubular injury rapidly reduce
      proximal tubular TLR4 content. Plasma membrane TLR4 release through glycine
      suppressible pores, possibly coupled with a translation block, appears to be
      involved. Rapid postinjury urinary TLR4 excretion suggests its potential utility
      as a "biomarker" of impending ARF.

PMID- 16885151
TI  - Characterization of cell clones isolated from hypoxia-selected renal proximal
      tubular cells.
AB  - Under hypoxia, some cells survive and others are irreversibly injured and die.
      The factors that determine cell fate under stress remain largely unknown. We
      recently selected death-resistant cells via repeated episodes of hypoxia. In the
      present study, 80 clones were isolated from the selected cells and their response
      to apoptotic injury was characterized. Compared with the wild-type cells, the
      isolated clones showed a general resistance to apoptosis: 13 were extremely
      resistant to azide-induced apoptosis, 10 to staurosporine, and 9 to cisplatin.
      The cell clones that most consistently demonstrated resistance or sensitivity to
      injury were further studied for their response to azide treatment. Azide induced
      comparable ATP depletion in these clones and wild-type cells. Hypoxia inducible
      factor-1 (HIF-1) was upregulated in several clones, but the upregulation did not
      correlate with cell death resistance. The selected clones maintained an
      epithelial phenotype, showing typical epithelial morphology, forming "domes" at
      high density, and expressing E-cadherin. Azide-induced Bax translocation and
      cytochrome c release, two critical mitochondrial events of apoptosis, were
      abrogated in death-resistant clones. In addition, cell lysates isolated from
      these clones showed lower caspase activation on addition of exogenous cytochrome
      c. Bax, Bak, and Bid expression in these clones was similar to that in wild-type
      cells, whereas Bcl-2 expression was higher in all the selected clones and,
      interestingly, Bcl-xL was markedly upregulated in the most death-resistant
      clones. The results suggest that apoptotic resistance of the selected clones is
      not determined by a single factor or molecule but, rather, by various alterations
      at the core apoptotic pathway.

PMID- 16885152
TI  - Renal expression of organic anion transporter OAT2 in rats and mice is regulated
      by sex hormones.
AB  - The renal reabsorption and/or excretion of various organic anions is mediated by
      specific organic anion transporters (OATs). OAT2 (Slc22a7) has been identified in
      rat kidney, where its mRNA expression exhibits gender differences [females (F) >
      males (M)]. The exact localization of OAT2 protein in the mammalian kidney has
      not been reported. Here we studied the expression of OAT2 mRNA by RT-PCR and its
      protein by Western blotting (WB) and immunocytochemistry (IC) in kidneys of adult
      intact and gonadectomized M and F, sex hormone-treated castrated M, and
      prepubertal M and F rats, and the protein in adult M and F mice. In adult rats,
      the expression of OAT2 mRNA was predominant in the outer stripe (OS) tissue,
      exhibiting 1) gender dependency (F > M), 2) upregulation by castration and
      downregulation by ovariectomy, and 3) strong downregulation by testosterone and
      weak upregulation by estradiol and progesterone treatment. A polyclonal antibody
      against rat OAT2 on WB of isolated renal membranes labeled a approximately 66-kDa
      protein band that was stronger in F. By IC, the antibody exclusively stained
      brush border (BB) of the proximal tubule S3 segment (S3) in the OS and medullary
      rays (F > M). In variously treated rats, the pattern of 66-kDa band density in
      the OS membranes and the staining intensity of BB in S3 matched the mRNA
      expression. The expression of OAT2 protein in prepubertal rats was low and gender
      independent. In mice, the expression pattern largely resembled that in rats.
      Therefore, OAT2 in rat (and mouse) kidney is localized to the BB of S3,
      exhibiting gender differences (F > M) that appear in puberty and are caused by
      strong androgen inhibition and weak estrogen and progesterone stimulation.

PMID- 16885153
TI  - Erythropoietin and the cardiorenal syndrome: cellular mechanisms on the
      cardiorenal connectors.
AB  - We have recently proposed severe cardiorenal syndrome (SCRS), in which cardiac
      and renal failure mutually amplify progressive failure of both organs. This
      frequent pathophysiological condition has an extremely poor prognosis.
      Interactions between inflammation, the renin-angiotensin system, the balance
      between the nitric oxide and reactive oxygen species and the sympathetic nervous
      system form the cardiorenal connectors and are cornerstones in the
      pathophysiology of SCRS. An absolute deficit of erythropoietin (Epo) and
      decreased sensitivity to Epo in this syndrome both contribute to the development
      of anemia, which is more pronounced than renal anemia in the absence of heart
      failure. Besides expression on erythroid progenitor cells, Epo receptors are
      present in the heart, kidney, and vascular system, in which activation results in
      antiapoptosis, proliferation, and possibly antioxidation and anti-inflammation.
      Interestingly, Epo can improve cardiac and renal function. We have therefore
      reviewed the literature with respect to Epo and the cardiorenal connectors.
      Indeed, there are indications that Epo can diminish inflammation, reduce renin
      angiotensin system activity, and shift the nitric oxide and reactive oxygen
      species balance toward nitric oxide. Information about Epo and the sympathetic
      nervous system is scarce. This analysis underscores the relevance of a further
      understanding of clinical and cellular mechanisms underlying protective effects
      of Epo, because this will support better treatment of SCRS.

PMID- 16885154
TI  - Urine concentrating defect in prostaglandin EP1-deficient mice.
AB  - We investigated the role of the prostaglandin E(2) (PGE(2)) EP(1) receptor in
      modulating urine concentration as it is expressed along the renal collecting duct
      where arginine-vasopressin (AVP) exerts its anti-diuretic activity, and in the
      paraventricular and supraoptic nuclei of the hypothalamus where AVP is
      synthesized. The urine osmolality of EP(1)-null mice (EP(1)(-/-)) failed to match
      levels achieved by wild-type (WT) counterparts upon water deprivation (WD) for 24
      h. This difference was reflected by higher plasma osmolality in WD EP(1)(-/-)
      mice. Along the collecting duct, the induction and subapical to plasma membrane
      translocation of the aquaporin-2 water channel in WD EP(1)(-/-) mice appeared
      equivalent to that of WD WT mice as determined by quantitative RT-PCR and
      immunohistochemistry. However, medullary interstitial osmolalities dropped
      significantly in EP(1)(-/-) mice following WD. Furthermore, urinary AVP levels of
      WD EP(1)(-/-) mice were significantly lower than those of WD WT mice. This
      deficit could be traced back to a blunted induction of hypothalamic AVP mRNA
      expression in WD EP(1)(-/-) mice as determined by quantitative RT-PCR.
      Administration of the AVP mimetic [deamino-Cys(1),D-Arg(8)]-vasopressin restored
      a significant proportion of the urine concentrating ability of WD EP(1)(-/-)
      mice. When mice were water loaded to suppress endogenous AVP production, urine
      osmolalities increased equally for WT and EP(1)(-/-) mice. These data suggest
      that PGE(2) modulates urine concentration by acting at EP(1) receptors, not in
      the collecting duct, but within the hypothalamus to promote AVP synthesis in
      response to acute WD.

PMID- 16885155
TI  - ERK promotes hydrogen peroxide-induced apoptosis through caspase-3 activation and
      inhibition of Akt in renal epithelial cells.
AB  - Reactive oxygen species, including hydrogen peroxide (H(2)O(2)), are generated
      during ischemia-reperfusion and are critically involved in acute renal failure.
      The present studies examined the role of the extracellular signal-regulated
      kinase (ERK) pathway in H(2)O(2)-induced renal proximal tubular cells (RPTC)
      apoptosis. Exposure of RPTC to 1 mM H(2)O(2) resulted in apoptosis and activation
      of ERK1/2 and Akt. Pretreatment with the specific MEK inhibitors, U0126 and
      PD98059, or adenoviral infection with a construct that encodes a negative mutant
      of MEK1, protected cells against H(2)O(2)-induced apoptosis. In contrast,
      expression of constitutively active MEK1 enhanced H(2)O(2)-induced apoptosis.
      H(2)O(2) induced activation of caspase-3 and phosphorylation of histone H2B at
      serine 14, a posttranslational modification required for nuclear condensation,
      which also were blocked by ERK1/2 inhibition. Furthermore, blockade of ERK1/2
      resulted in an increase in Akt phosphorylation and blockade of Akt potentiated
      apoptosis and diminished the protective effect conferred by ERK inhibition in
      H(2)O(2)-treated cells. Although Z-DEVD-FMK, a caspase-3 inhibitor, was able to
      inhibit histone H2B phosphorylation and apoptosis, it did not affect ERK1/2
      phosphorylation. We suggest that ERK elicits apoptosis in epithelial cells by
      activating caspase-3 and inhibiting Akt pathways and elicits nuclear condensation
      through caspase-3 and histone H2B phosophorylation during oxidant injury.

PMID- 16885157
TI  - Transgenic mice expressing dominant-negative activin receptor IB in forebrain
      neurons reveal novel functions of activin at glutamatergic synapses.
AB  - The transforming growth factor beta family member activin is an important
      regulator of development and tissue repair. It is strongly up-regulated after
      acute injury to the adult brain, and application of exogenous activin protects
      neurons in several lesion models. To explore the role of endogenous activin in
      the normal and acutely damaged brain, we generated transgenic mice expressing a
      dominant-negative activin receptor IB (dnActRIB) mutant in forebrain neurons. The
      functionality of the transgene was verified in vivo. Hippocampal neurons from
      dnActRIB mice were significantly more vulnerable to intracerebroventricular
      injection of the excitotoxin kainic acid than those from control littermates,
      indicating a crucial role of endogenous activin in the rescue of neurons from
      excitotoxic insult. Because dnActRIB is only expressed in neurons, but not in
      glial cells, activin affords protection at least in part through a direct action
      on endangered neurons. Unexpectedly, the transgenic mice also revealed a
      prominent novel role of activin in glutamatergic neurotransmission in the intact
      adult brain. Electrophysiologic examination of excitatory synapses onto CA1
      pyramidal cells in hippocampal slices of dnActRIB mice showed a reduced NMDA
      current response, which was associated with impaired long term potentiation. This
      is the first demonstration that activin receptor signaling is essential to
      optimize the performance of neuronal circuits in the mature brain under
      physiological conditions.

PMID- 16885156
TI  - Insulin regulation of cholesterol 7alpha-hydroxylase expression in human
      hepatocytes: roles of forkhead box O1 and sterol regulatory element-binding
      protein 1c.
AB  - Bile acid synthesis and pool size increases in diabetes, whereas insulin inhibits
      bile acid synthesis. The objective of this study is to elucidate the mechanism of
      insulin regulation of cholesterol 7alpha-hydroxylase gene expression in human
      hepatocytes. Real-time PCR assays showed that physiological concentrations of
      insulin rapidly stimulated cholesterol 7alpha-hydroxylase (CYP7A1) mRNA
      expression in primary human hepatocytes but inhibited CYP7A1 expression after
      extended treatment. The insulin-regulated forkhead box O1 (FoxO1) and steroid
      regulatory element-binding protein-1c (SREBP-1c) strongly inhibited hepatocyte
      nuclear factor 4alpha and peroxisome proliferator-activated receptor gamma
      coactivator-1alpha trans-activation of the CYP7A1 gene. FoxO1 binds to an insulin
      response element in the rat CYP7A1 promoter, which is not present in the human
      CYP7A1 gene. Insulin rapidly phosphorylates and inactivates FoxO1, whereas
      insulin induces nuclear SREBP-1c expression in human primary hepatocytes.
      Chromatin immunoprecipitation assay shows that insulin reduced FoxO1 and
      peroxisome proliferators-activated receptor gamma-coactivator-1alpha but
      increased SREBP-1c recruitment to CYP7A1 chromatin. We conclude that insulin has
      dual effects on human CYP7A1 gene transcription; physiological concentrations of
      insulin rapidly inhibit FoxO1 activity leading to stimulation of the human CYP7A1
      gene, whereas prolonged insulin treatment induces SREBP-1c, which inhibits human
      CYP7A1 gene transcription. Insulin may play a major role in the regulation of
      bile acid synthesis and dyslipidemia in diabetes.

PMID- 16885158
TI  - Regulation of neuronal morphology by Toca-1, an F-BAR/EFC protein that induces
      plasma membrane invagination.
AB  - Actin reorganization is important for regulation of neuronal morphology. Neural
      Wiskott-Aldrich syndrome protein (N-WASP) is an important regulator of actin
      polymerization and also known to be strongly expressed in brain. Recently, Toca-1
      (transducer of Cdc42-dependent actin assembly) has been shown to be required for
      Cdc42 to activate N-WASP from biochemical experiments. Toca-1 has three
      functional domains: an F-BAR/EFC domain at the N terminus, an HR1 at the center,
      and an SH3 domain at the C terminus. The F-BAR/EFC domain induces tubular
      invagination of plasma membrane, while Toca-1 binds both N-WASP and Cdc42 through
      the SH3 domain and the HR1, respectively. However, the physiological role of Toca
      1 is completely unknown. Here we have investigated the neural function of Toca-1.
      Toca-1 is strongly expressed in neurons including hippocampal neurons in
      developing brain at early times. Knockdown of Toca-1 in PC12 cells significantly
      enhances neurite elongation. Consistently, overexpression of Toca-1 suppresses
      neurite elongation through the F-BAR/EFC domain with a membrane invaginating
      property, suggesting an implication of membrane trafficking in the neural
      function of Toca-1. In addition, knockdown of N-WASP, to our surprise, also
      enhances neurite elongation in PC12 cells, which is in clear contrast to the
      previous report that dominant negative mutants of N-WASP suppress neurite
      extension in PC12 cells. On the other hand, knockdown of Toca-1 in cultured rat
      hippocampal neurons enhances axon branching a little but not axon elongation,
      while knockdown of N-WASP enhances both axon elongation and branching. These
      results suggest that a vesicle trafficking regulator Toca-1 regulates different
      aspects of neuronal morphology from N-WASP.

PMID- 16885159
TI  - ATP-consuming and ATP-generating enzymes secreted by pancreas.
AB  - Pancreatic acini release ATP in response to various stimuli, including
      cholecystokinin octapeptide (CCK-8), as we show in the present study. There were
      indications that pancreatic juice also contains enzymes that could hydrolyze ATP
      during its passage through the ductal system. The aim of this study was to
      determine which ATP-degrading and possibly ATP-generating enzymes were present in
      pancreatic secretion. For this purpose, pancreatic juice was collected from
      anesthetized rats stimulated with infusion of CCK-8. Purine-converting activities
      in juice samples were assayed by TLC using either [gamma-(32)P]ATP or (14)C/(3)H
      labeled and unlabeled nucleotides as appropriate substrates. Data show that the
      juice contains the enzyme ecto-nucleoside triphosphate diphosphohydrolase that
      can hydrolyze both [(14)C]ATP and [(3)H]ADP about equally well, i.e. CD39.
      Reverse-phase high-performance liquid chromatography analysis additionally shows
      that this enzyme has broad substrate specificity toward other nucleotides, UTP,
      UDP, ITP, and IDP. In addition, secretion contains ecto-5'-nucleotidase, CD73,
      further converting [(3)H]AMP to adenosine. Along with highly active hydrolytic
      enzymes, there were also ATP-generating enzymes in pancreatic juice, adenylate
      kinase, and NDP kinase, capable of sequentially phosphorylating AMP via ADP to
      ATP. Activities of nonspecific phosphatases, nucleotide
      pyrophosphatase/phosphodiesterases, and adenosine deaminase were negligible.
      Taken together, CCK-8 stimulation of pancreas causes release of both ATP
      consuming and ATP-generating enzymes into pancreatic juice. This newly discovered
      richness of secreted enzymes underscores the importance of purine signaling
      between acini and pancreatic ducts lumen and implies regulation of the purine
      converting enzymes release.

PMID- 16885160
TI  - ChREBP*Mlx is the principal mediator of glucose-induced gene expression in the
      liver.
AB  - In mammals, glucose-regulated gene expression has been best characterized in the
      liver, where increased glucose metabolism induces transcription of genes encoding
      enzymes involved in de novo lipogenesis. ChREBP and Mlx dimerize and function
      together as a glucose-responsive transcription factor to regulate target genes,
      such as liver-type pyruvate kinase, acetyl-CoA carboxylase 1, and fatty acid
      synthase. To identify additional glucose-responsive genes in the liver, we used
      microarray analysis to compare gene expression patterns in low and high glucose
      conditions in hepatocytes. Target genes of ChREBP.Mlx were simultaneously
      identified by gene profiling in the presence or absence of a dominant negative
      Mlx. Of 224 genes that are induced by glucose, 139 genes (62%) were also
      inhibited by the dominant negative Mlx. Lipogenic enzyme genes involved in the
      entire pathway of de novo lipogenesis were found to be glucose-responsive target
      genes of ChREBP.Mlx. Genes encoding enzymes in other metabolic pathways and
      numerous regulators of metabolism were also identified. To determine if any of
      these genes are direct targets of ChREBP.Mlx, we searched for ChoRE-like
      sequences in the 5'-flanking regions of several genes that responded rapidly to
      glucose. ChoRE sequences that bound to ChREBP.Mlx and supported a glucose
      response were identified in two additional genes. Combining all of the known
      ChoRE sequences, we generated a modified ChoRE consensus sequence,
      CAYGNGN(5)CNCRTG. In summary, ChREBP.Mlx is the principal transcription factor
      regulating glucose-responsive genes in the liver and coordinately regulates a
      family of genes required for glucose utilization and energy storage.

PMID- 16885161
TI  - Determinants of Rbp1p localization in specific cytoplasmic mRNA-processing foci,
      P-bodies.
AB  - Rbp1p, a yeast RNA-binding protein, decreases the level of mitochondrial porin
      mRNA by enhancing its degradation, but the intracellular location of the Rbp1p
      mediated degradation complex remains unknown. We show here that Rbp1p in
      xrn1Delta mutant yeast localizes in specific cytoplasmic foci that are known as P
      bodies. The N-terminal and RNA recognition motif (RRM) 1 domains of Rbp1p are
      necessary but not sufficient for its localization in P bodies. Rbp1p forms
      oligomers through its C-terminal domain in vivo; N-terminal-delete, or RRM1
      mutated Rbp1p can be more efficiently recruited to P-bodies in an xrn1Delta
      strain, expressing a full-length Rbp1p. Although POR1 mRNA is localized to P
      bodies in an xrn1Delta strain, this localization does not depend on Rbp1p.
      Decapping activator Dhh1p directly interacts with Rbp1p. However, the recruitment
      of Rbp1p to P-bodies does not require Dhh1p or Ccr4p. In wild-type cells, Rbp1p
      can localize to P-bodies under glucose deprivation or treatment with KCl. In
      addition, Rbp1p-mediated porin mRNA decay is elicited by Xrn1p, a 5 ' to 3 '
      exonuclease. These results provide new insight into the mechanism of Rbp1p
      function.

PMID- 16885162
TI  - Expression of mouse Abcg2 mRNA during hematopoiesis is regulated by alternative
      use of multiple leader exons and promoters.
AB  - ABCG2 encodes a transmembrane transporter associated with multidrug resistance in
      various cancer cells. ABCG2 is also highly expressed in hematopoietic stem cells
      (HSCs) and is down-regulated in most committed progenitors, whereas expression is
      sharply up-regulated during erythroid differentiation. The mechanisms for
      regulation of ABCG2 expression in hematopoietic cells are poorly understood. We
      have recently identified three novel leader exons (termed E1A, E1B, and E1C)
      located in the 5'-untranslated region of mouse Abcg2 mRNA by data base searches
      and reverse transcription-PCR. In a mouse erythroid cell line, reverse
      transcription-PCR analysis showed that the transcript containing E1B exon was the
      only isoform detected. Consistently, the E1B-containing transcript was the
      predominant isoform of Abcg2 mRNA in primary Ter119+ erythroid cells from mouse
      bone marrow as well as in mouse fetal liver cells. In contrast, the E1A
      containing transcript was highly expressed in c-Kit+, Sca-1+, Lin- (KSL) bone
      marrow cells, especially in CD34- KSL fraction, which is highly enriched for
      repopulating HSCs. The differential expression pattern of Abcg2 mRNA isoforms in
      mouse HSCs and erythroid cells was confirmed by 5'-rapid amplification of cDNA
      ends, indicating that at least two different promoters control mouse Abcg2
      transcription during hematopoiesis. Promoter functional assays using EGFP as
      reporter gene demonstrated that the E1A 5'-flanking region had promoter activity,
      which contains multiple putative hematopoietic transcription factor binding
      sites. In summary, our data show that the expression of Abcg2 during
      hematopoiesis is transcriptionally regulated by alternative use of multiple
      leader exons and promoters in a developmental stage-specific manner.

PMID- 16885163
TI  - Protein-protein interactions in the archaeal transcriptional machinery: binding
      studies of isolated RNA polymerase subunits and transcription factors.
AB  - Transcription in Archaea is directed by a pol II-like RNA polymerase and
      homologues of TBP and TFIIB (TFB) but the crystal structure of the archaeal
      enzyme and the subunits involved in recruitment of RNA polymerase to the promoter
      TBP-TFB-complex are unknown. We described here the cloning expression and
      purification of 11 bacterially expressed subunits of the Pyrococcus furiosus
      RNAP. Protein interactions of subunits with each other and of archaeal
      transcription factors TFB and TFB with RNAP subunits were studied by Far-Western
      blotting and reconstitution of subcomplexes from single subunits in solution. In
      silico comparison of a consensus sequence of archaeal RNAP subunits with the
      sequence of yeast pol II subunits revealed a high degree of conservation of
      domains of the enzymes forming the cleft and catalytic center of the enzyme.
      Interaction studies with the large subunits were complicated by the low
      solubility of isolated subunits B, A', and A'', but an interaction network of the
      smaller subunits of the enzyme was established. Far-Western analyses identified
      subunit D as structurally important key polypeptide of RNAP involved in
      interactions with subunits B, L, N, and P and revealed also a strong interaction
      of subunits E' and F. Stable complexes consisting of subunits E' and F, of D and
      L and a BDLNP-subcomplex were reconstituted and purified. Gel shift analyses
      revealed an association of the BDLNP subcomplex with promoter-bound TBP-TFB.
      These results suggest a major role of subunit B (Rpb2) in RNAP recruitment to the
      TBP-TFB promoter complex.

PMID- 16885164
TI  - The length of peptide substrates has a marked effect on hydroxylation by the
      hypoxia-inducible factor prolyl 4-hydroxylases.
AB  - Three hypoxia-inducible factor prolyl 4-hydroxylases (HIF-P4Hs) regulate the HIFs
      by hydroxylating prolines at two separate sites in the oxygen-dependent
      degradation domain (ODDD) of their alpha subunits. We compared in vitro
      hydroxylation by purified recombinant human HIF-P4Hs of 19-20- and 35-residue
      peptides corresponding to the two sites in HIF-alphas and purified recombinant
      HIF-1alpha and HIF-2alpha ODDDs of 248 and 215 residues. The increase in the
      length of peptides representing the C-terminal site from 19 to 20 to 35 residues
      reduced the K(m) values to 90-800 nm, i.e. to 0.7-11% of those for the shorter
      peptides, whereas those representing the N-terminal site were 10-470 microm, i.e.
      10-135%. The K(m) values of HIF-P4H-1 for the recombinant HIF-alpha ODDDs were 10
      20 nm, whereas those of HIF-P4H-2 and -3 were 60-140 nm, identical values being
      found for the wild-type HIF-1alpha ODDD and its N site mutant. The K(m) values
      for the C site mutant were about 5-10 times higher but only 0.2-3% of those for
      the 35-residue N site peptides, and this marked difference suggested that the HIF
      P4Hs may become bound first to the C-terminal site of an ODDD and that this
      binding may enhance subsequent binding to the N-terminal site. The K(m) values of
      HIF-P4H-2 for oxygen determined with the HIF-1alpha ODDD and both its mutants as
      substrates were all about 100 microm, being 40% of those reported for the three
      HIF-P4Hs with a 19-residue peptide. Even this value is high compared with tissue
      O(2) levels, indicating that HIF-P4Hs are effective oxygen sensors.

PMID- 16885165
TI  - No change in glomerular heparan sulfate structure in early human and experimental
      diabetic nephropathy.
AB  - Heparan sulfate (HS) proteoglycans are major anionic glycoconjugates of the
      glomerular basement membrane and are thought to contribute to the permeability
      properties of the glomerular capillary wall. In this study we evaluated whether
      the development of (micro) albuminuria in early human and experimental diabetic
      nephropathy is related to changes in glomerular HS expression or structure. Using
      a panel of recently characterized antibodies, glomerular HS expression was
      studied in kidney biopsies of type I diabetic patients with microalbuminuria or
      early albuminuria and in rat renal tissue after 5 months diabetes duration.
      Glomerular staining, however, revealed no differences between control and
      diabetic specimens. A significant (p < 0.05) approximately 60% increase was found
      in HS N-deacetylase activity, a key enzyme in HS sulfation reactions, in diabetic
      glomeruli. Structural analysis of glomerular HS after in vivo and in vitro
      radiolabeling techniques revealed no changes in HS N-sulfation or charge density.
      Also HS chain length, protein binding properties, as well as disaccharide
      composition did not differ between control and diabetic glomerular HS samples.
      These results indicate that in experimental and early human diabetic nephropathy,
      increased urinary albumin excretion is not caused by loss of glomerular HS
      expression or sulfation and suggest other mechanisms to be responsible for
      increased glomerular albumin permeability.

PMID- 16885166
TI  - Crystal structure of aminopeptidase N (proteobacteria alanyl aminopeptidase) from
      Escherichia coli and conformational change of methionine 260 involved in
      substrate recognition.
AB  - Aminopeptidase N from Escherichia coli is a broad specificity zinc exopeptidase
      belonging to aminopeptidase clan MA, family M1. The structures of the ligand-free
      form and the enzyme-bestatin complex were determined at 1.5- and 1.6-A
      resolution, respectively. The enzyme is composed of four domains: an N-terminal
      beta-domain (Met(1)-Asp(193)), a catalytic domain (Phe(194)-Gly(444)), a middle
      beta-domain (Thr(445)-Trp(546)), and a C-terminal alpha-domain (Ser(547)
      Ala(870)). The structure of the catalytic domain exhibits similarity to
      thermolysin, and a metal-binding motif (HEXXHX(18)E) is found in the domain. The
      zinc ion is coordinated by His(297), His(301), Glu(320), and a water molecule.
      The groove on the catalytic domain that contains the active site is covered by
      the C-terminal alpha-domain, and a large cavity is formed inside the protein.
      However, there exists a small hole at the center of the C-terminal alpha-domain.
      The N terminus of bestatin is recognized by Glu(121) and Glu(264), which are
      located in the N-terminal and catalytic domains, respectively. Glu(298) and
      Tyr(381), located near the zinc ion, are considered to be involved in peptide
      cleavage. A difference revealed between the ligand-free form and the enzyme
      bestatin complex indicated that Met(260) functions as a cushion to accept
      substrates with different N-terminal residue sizes, resulting in the broad
      substrate specificity of this enzyme.

PMID- 16885168
TI  - Effects of temperature gradient correction of carbon dioxide absorbent on carbon
      dioxide absorption.
AB  - BACKGROUND: The effects of temperature gradients in CO(2) absorbents on water
      content and CO(2) absorption are not clear. We constructed a novel temperature
      gradient correction (TGC) canister, and investigated the effects of temperature
      gradient correction on the water content and longevity (time to exhaustion) of
      CO(2) absorbent using a simulated anaesthesia circuit. METHODS: Experiments were
      divided into two groups according to the type of canister used: the TGC canister
      (n=6) or the conventional canister (n=6). One kilogram of fresh CO(2) absorbent
      was placed into the canister. The anaesthetic ventilator was connected to a 3
      litre bag and 300 ml min(-1) of CO(2) was introduced. Oxygen (500 ml min(-1)) was
      used as fresh gas. The anaesthetic ventilator was set at a ventilatory frequency
      of 12 bpm, and tidal volume was adjusted to 700 ml. RESULTS: Before the
      experiment, the water content of the fresh CO(2) absorbent in the conventional
      canister and TGC canister was 16.1 (0.9)% and 15.7 (1.1)%, respectively. After
      the experiment, the water content of CO(2) absorbent near the upper outer rim of
      the canister increased to 32.4 (0.7)% in the conventional canister, but increased
      to only 20.6 (1.3)% in the TGC canister (P<0.01). The longevity of CO(2)
      absorbent in the conventional canister and TGC canister was 434 (9) min and 563
      (13) min (P<0.01). CONCLUSIONS: Temperature gradient correction prevented a local
      excessive increase in water content and improved the longevity of CO(2)
      absorbent.

PMID- 16885167
TI  - Proteinase-activated receptors, targets for kallikrein signaling.
AB  - Serine proteinases like thrombin can signal to cells by the cleavage/activation
      of proteinase-activated receptors (PARs). Although thrombin is a recognized
      physiological activator of PAR(1) and PAR(4), the endogenous enzymes responsible
      for activating PAR(2) in settings other than the gastrointestinal system, where
      trypsin can activate PAR(2), are unknown. We tested the hypothesis that the human
      tissue kallikrein (hK) family of proteinases regulates PAR signaling by using the
      following: 1) a high pressure liquid chromatography (HPLC)-mass spectral analysis
      of the cleavage products yielded upon incubation of hK5, -6, and -14 with
      synthetic PAR N-terminal peptide sequences representing the cleavage/activation
      motifs of PAR(1), PAR(2), and PAR(4); 2) PAR-dependent calcium signaling
      responses in cells expressing PAR(1), PAR(2), and PAR(4) and in human platelets;
      3) a vascular ring vasorelaxation assay; and 4) a PAR(4)-dependent rat and human
      platelet aggregation assay. We found that hK5, -6, and -14 all yielded PAR
      peptide cleavage sequences consistent with either receptor activation or
      inactivation/disarming. Furthermore, hK14 was able to activate PAR(1), PAR(2),
      and PAR(4) and to disarm/inhibit PAR(1). Although hK5 and -6 were also able to
      activate PAR(2), they failed to cause PAR(4)-dependent aggregation of rat and
      human platelets, although hK14 did. Furthermore, the relative potencies and
      maximum effects of hK14 and -6 to activate PAR(2)-mediated calcium signaling
      differed. Our data indicate that in physiological settings, hKs may represent
      important endogenous regulators of the PARs and that different hKs can have
      differential actions on PAR(1), PAR(2), and PAR(4).

PMID- 16885170
TI  - Correlation of microalbuminuria and outcome in patients with extensive burns.
AB  - BACKGROUND: Microalbuminuria, often referred to as the urinary albumin-creatinine
      ratio (ACR), is thought to be a reflection of increased capillary permeability
      associated with the systemic inflammatory response syndrome, and has been found
      to be predictive of outcome in several studies. Therefore, we explored the
      usefulness of ACR as a predictor of mortality, and whether there was a
      correlation between ACR and PaO2/ FIO2 ratios in patients with extensive burns.
      METHODS: A retrospective observational study was carried out on all patients with
      extensive burns admitted to the burns intensive care unit. All adult patients
      with burns of at least 40%, or those with significant inhalational injury, were
      included. Exclusion criteria were paediatric patients or those with non-thermal
      processes such as Stevens-Johnson's syndrome. ACR was measured daily, and data
      including PaO2/ FIO2 ratios were collected. The outcome studied was mortality.
      RESULTS: A total of 21 patients were studied, of which there were 7 mortalities.
      Data were analysed using SPSS Ver11. Patient characteristic data between
      survivors and mortalities were similar. We did not find any correlation between
      trends of ACR with PaO2/ FIO2 ratios. However, in non-survivors, there were two
      peaks in ACR, an early peak at days 8-9, and a later peak at day 32, whereas
      concentrations remained stable in survivors. CONCLUSION: We conclude that while
      ACR is useful as a predictor of mortality and that mean ACR of more than 20 mg
      mmol(-1)is associated with poorer outcome, changes in ACR do not reflect changes
      in the patients' immediate clinical conditions.

PMID- 16885169
TI  - Alleviation of neuropathic pain by intrathecal injection of antisense
      oligonucleotides to p65 subunit of NF-kappaB.
AB  - BACKGROUND: Treatment of neuropathic pain remains a challenge. The current study
      investigated the therapeutic effect of intrathecal administration of NF-kappaB
      antisense oligodeoxynucleotides (ODNs) on mechanical allodynia and thermal
      hyperalgesia in a chronic constriction injury (CCI) model of rats. METHODS:
      Lumbar intrathecal catheters were implanted in male Sprague-Dawley rats and a CCI
      model was established. Thermal and mechanical nociceptive thresholds were
      assessed with paw withdrawal latency (PWL) to radiant heat and von Frey
      filaments. The phosphorothioate-modified antisense ODNs to p65 subunit of NF
      kappaB were administered intrathecally on each of five consecutive days post-CCI.
      Nuclear NF-kappaB p65 expression was assessed by western blot. RESULTS: CCI
      induced mechanical allodynia and thermal hyperalgesia and significantly increased
      NF-kappaB p65 protein expression. Intrathecal injection of antisense ODN markedly
      suppressed the expression of NF-kappaB p65 protein and significantly attenuated
      CCI-induced mechanical allodynia and thermal hyperalgesia. CONCLUSION: The
      activation of NF-kappaB pathway may contribute to neuropathic pain in CCI rats.
      Suppression of NF-kappaB could be a potential new strategy for the treatment of
      neuropathic pain.

PMID- 16885171
TI  - A comparison of postoperative pain scales in neonates.
AB  - BACKGROUND: Practical, valid and reliable pain measuring tools in neonates are
      required in clinical practice for effective pain management and prevention of the
      evaluator bias. METHODS: This prospective study was designed to cross-validate
      three pain scales: CRIES (cry, requires O(2), increased vital signs, expression,
      sleeplessness), CHIPPS (children's and infants' postoperative pain scale) and
      NIPS (neonatal infant pain scale) in terms of validity, reliability and
      practicality. The pain scales were translated. Concurrent validity, predictive
      validity and interrater reliability in postoperative pain were studied in 22
      neonates after major surgery. Construct validity and concurrent validity in
      procedural pain were determined in 24 neonates before and during frenulectomy
      under topical anaesthesia. RESULTS: All scales had excellent interrater
      reliability (intraclass correlation >0.9). Construct validity was determined for
      all pain scales by the ability to differentiate the group with low pain scores
      before surgery and high scores during surgery (P<0.001). The positive
      correlations among all scales, ranging between r=0.30 and r=0.91, supported
      concurrent validity. CRIES showed the lowest correlation with other scales with
      correlation coefficients of r=0.30 and r=0.35. All scales yielded very good
      agreement (K>0.9) with routine decisions to treat postoperative pain. High
      sensitivity and specificity (>90%) for postoperative pain from all scales were
      achieved with the same cut-off point of 4. In terms of practicality, NIPS was the
      most acceptable (65%). CONCLUSIONS: Based on our findings, we recommended NIPS as
      a valid, reliable and practical tool.

PMID- 16885172
TI  - Efficacy of fibrinogen and prothrombin complex concentrate used to reverse
      dilutional coagulopathy--a porcine model.
AB  - BACKGROUND: This study was conducted to assess whether the combined
      administration of fibrinogen and prothrombin complex concentrate (PCC) enables
      the reversal of dilutional coagulopathy resulting from intended blood loss and
      fluid replacement, and whether this treatment reduces further blood loss and
      mortality. METHODS: In 20 anaesthetized pigs, approximately 65% of the estimated
      blood volume was withdrawn and replaced with the same amount of hydroxyethyl
      starch (6% HES 130/0.4) to mimic blood loss and to develop a dilutional
      coagulopathy. Pigs (randomized) received either fibrinogen (200 mg kg(-1)) and
      PCC (35 IU kg(-1)) (n=10), or placebo (n=10). Thereafter, a standard liver
      laceration was performed to induce uncontrolled haemorrhage. The subsequent blood
      loss and survival time were determined as primary outcome variables. Throughout
      the experiment serial blood samples were obtained to assess the competence of the
      haemostatic system using standard coagulation tests, modified Thrombelastograph
      measurements (ROTEM) and electron microscopy clot imaging. RESULTS: As compared
      with baseline, after haemodilution both groups showed statistically significant
      impairment of haemostasis as measured with standard coagulation tests and
      thrombelastography. These parameters significantly improved after administration
      of the study drugs while aPPT measurements remained unchanged. Blood loss after
      liver injury was significantly less in the treatment group as compared with
      placebo: 240 ml (50-830) vs 1800 ml (1500-2500) (P<0.0001). All treated animals
      survived, whereas 80% of the placebo group died (P<0.0001). CONCLUSION: During
      haemodilution, substitution of fibrinogen and PCC causes an enhancement of
      coagulation and final clot strength. This reversal of dilutional coagulopathy may
      reduce blood loss and mortality when large amounts of colloids are needed to
      maintain normovolaemia during huge blood losses.

PMID- 16885173
TI  - The extent and nature of food promotion directed to children in Australian
      supermarkets.
AB  - The aim of this study was to describe the nature and amount of sales promotion
      use on food packaging in selected Australian supermarkets, specifically those
      directed at children through the use of premium offers, such as giveaways and
      competitions, and cartoon and movie character promotions. The study also examined
      the promotion of healthy versus unhealthy foods. Nine supermarkets located across
      the metropolitan area of Sydney, Australia were surveyed to assess the extent and
      nature of food promotion directed at children. The number and types of promotions
      were measured within seven food categories: sweet biscuits, snack foods,
      confectionery, chips/savoury snacks, cereals, dairy snacks and ice cream. Any
      foods that utilized promotional tactics were categorized as either healthy or
      unhealthy, according to set criteria. The study found that within the seven food
      categories between 9 and 35% of food products used promotional tactics. The use
      of television, movie celebrities and cartoon characters for promotion was most
      common, making up 75% of all promotions. Giveaways accounted for 13% of all
      promotions. When used, giveaways were commonly used in conjunction with another
      promotional method. Data from this study also confirmed that 82% of all food
      promotions were for unhealthy foods and only 18% were used to promote healthy
      foods. However, for dairy snacks and ice cream the majority of promotions, 99 and
      65%, respectively, were healthier choices. This was the first study to describe
      the extent and nature of food promotions used in supermarkets. The promotion of
      unhealthy foods in supermarkets is common and is one of the many factors
      contributing to today's obesity promoting environment. Further research is
      required to determine the impact of food promotions on children's dietary intake,
      and to determine the most effective ways to restrict the promotion of unhealthy
      foods.

PMID- 16885174
TI  - Radiation doses to patients undergoing standard radiographic examinations: a
      comparison between two methods.
AB  - The objective of the study was to derive a mathematical method for calculating
      the entrance surface dose (ESD) from exposure factors for all tube potentials
      used in clinical practice and to compare the calculated ESDs (ESD(C)) with those
      measured (ESD(TLD)) using thermoluminescent dosemeters (TLDs). The exposure
      parameters of 43 patients who underwent (a) posteroanterior (PA) and lateral
      (LAT) chest examination (13 patients), (b) supine abdomen (10 patients), (c)
      erectus abdomen (10 patients), or (d) urinary tract examination (10 patients)
      were recorded. Patient ESD was directly measured by TLDs and calculated from
      exposure factors. The differences between ESD(C) and ESD(TLD) were quite small
      and could be explained by the uncertainties involved in both methods, in all but
      the PA chest examination where the ESD(C) was about 50% larger than ESD(TLD).
      However, in PA chest the ESD(TLD) was close to the minimum detectable dose of
      TLDs, questioning the accuracy of ESD(TLD). Further investigation showed that
      using the high tube potential technique (130 kV) in the PA chest examination
      resulted in very short exposure times, in the region of 4 ms. In such short
      exposure times, the X-ray generator operation presented stability problems that
      led to loss of output linearity and consequently to false calculation of ESD. The
      calculation method offers a reliable and cheap alternative to the measurement of
      ESD by TLD, provided that the exposure times are not as short as in the PA chest
      examinations recorded in this study, so that the output linearity with tube
      current-time product (mAs) is maintained.

PMID- 16885175
TI  - Reporting overexposures and unintended exposures in diagnostic procedures.
AB  - Legislation requires the reporting to regulatory authorities of incidents in
      which patients have been exposed to ionizing radiation to an extent "much greater
      than that intended". The authorities have published guidance on what is
      considered to meet this requirement. However, there is still some confusion
      regarding, particularly, the necessity to report some unintended doses. It is
      believed that there is a disproportionate amount of resource spent investigating
      some unintended exposures because all such exposures will have an effective
      overexposure factor of infinity, irrespective of the magnitude of the dose and
      the associated risk. This paper proposes changing the definitions of
      "overexposure" and "unintended exposure" and the adoption of a reporting process
      based upon risk assessment. All records and data would be collected and, if
      required, reported, but investigation of individual incidents would take place
      only for incidents carrying a greater risk than 1 in 10,000.

PMID- 16885176
TI  - Acquisition of MR perfusion images and contrast-enhanced MR angiography in acute
      ischaemic stroke patients: which procedure should be done first?
AB  - Multimodal MRI for acute ischaemic stroke usually includes perfusion imaging (PI)
      and contrast-enhanced neck MR angiography (CE-MRA), as well as diffusion-weighted
      imaging and T2* weighted imaging. Because both PI and CE-MRA require the infusion
      of contrast medium, the likelihood exists that one study may conflict with the
      other due to the accumulation of previously injected contrast medium. The purpose
      of this study is to determine the appropriate order of PI and CE-MRA in this
      multimodal MRI protocol for evaluation of acute ischaemic stroke. We studied 35
      patients with acute ischaemic stroke in the unilateral middle cerebral artery
      territory. 17 patients underwent CE-MRA following PI (group A) and 18 patients
      underwent PI following CE-MRA (group B). For qualitative analysis of the CE-MRA
      and colour-coded maps of the PI, two independent observers graded the image
      quality. Interobserver agreement was assessed using kappa statistics, and we
      assessed the statistical differences of imaging quality between groups A and B
      using the Mann-Whitney U-test). For the quantitative analysis of PI, two
      parameters--the maximum change in the transverse relaxation rate (DeltaR2(max))
      and the relative signal drop (DeltaS/S(0))--were calculated from the time-signal
      intensity curve of an unaffected middle cerebral artery territory, and we
      compared the differences in the parameters of group A and B (t-test).
      Interobserver agreements for CE-MRA and PI were good. In the qualitative analysis
      of CE-MRA and PI, no significant difference was observed between groups A and B.
      In the quantitative analysis of PI, there were no relevant differences in
      DeltaR2(max) and DeltaS/S(0) between the two groups. In simultaneous CE-MRA and
      PI, there was no deterioration of diagnostic imaging quality with regard to the
      order of the two post-contrast sequences. They can be performed according to the
      preference of each institution.

PMID- 16885177
TI  - Dose escalation to combat hypoxia in prostate cancer: a radiobiological study on
      clinical data.
AB  - Earlier studies have demonstrated that hypoxic regions exist in human prostate
      cancer and the degree of hypoxia correlates with the treatment outcome of
      radiotherapy. Using the concept of the clinical oxygen enhancement ratio (COER),
      the linear-quadratic (LQ) model was extended to account for the effect of tumour
      hypoxia. The clinical data collected at the Fox Chase Cancer Center for prostate
      cancer were analysed based on the LQ model as well as the tumour control
      probability (TCP) model. The LQ and TCP parameters (alpha = 0.15 Gy (-1),
      alpha/beta = 3.1 Gy and the number of clonogens K = 10(6) approximately 10(7)
      cells) determined in earlier studies were used to derive the COER for prostate
      cancer: COER = 1.4 with a standard confidence interval (CI) of (1.2, 1.8). The
      result is consistent with the in vitro OER measurements of human tumour cell
      lines under chronic hypoxia conditions. This implies that a higher dose is needed
      to overcome tumour hypoxia. For prostate tumours, the prescription dose required
      to overcome tumour hypoxia is 165 Gy (CI: 153 approximately 186 Gy) for permanent
      125I implants and 88 Gy (CI: 74 approximately 118 Gy) in 2 Gy fractions for
      external-beam radiotherapy. The impact of LQ parameters on the calculations of
      COER and dose escalation was discussed. This study provides a preliminary
      estimate of the dose escalation needed to overcome tumour hypoxia based on
      clinical data. More clinical data with better statistics and longer follow-up
      time are required to further tune the radiobiological modelling of hypoxia for
      prostate cancer.

PMID- 16885178
TI  - Oesophageal dysmotility in systemic sclerosis: comparison of HRCT and
      scintigraphy.
AB  - The aim of this study was to compare oesophageal abnormalities observed in high
      resolution CT with radionuclide transit in patients with systemic sclerosis. 76
      patients with systemic sclerosis were evaluated by high-resolution CT and
      oesophageal transit scintigraphy. Residual activity > or =20% (in relation to
      peak activity) at 15 s after the beginning of the swallow of the labelled liquid
      (in supine position) was considered indicative of oesophageal dysfunction. Supra
      aortic and infra-aortic oesophageal coronal diameters were measured in high
      resolution CT. Oesophageal dilatation was deemed present when the diameters
      exceeded 10 mm. 19 patients (25%) had supra-aortic oesophageal dilatation and 48
      patients (63.1%) had infra-aortic dilatation. The prevalence of radionuclide
      transit delay was 77.6%. All patients (19/19) with supra-aortic dilatation had
      oesophageal dysfunction, compared with 70.2% (40/57) of the patients with no
      supra-aortic dilatation (p = 0.004). Oesophageal dysfunction was present in 97.9%
      (47/48) of patients with infra-aortic dilatation, compared with 42.9% (12/28) in
      patients without it (p < 0.001). Receiver operating characteristic (ROC) curves
      have demonstrated that the supra-aortic and infra-aortic diameters had good
      discriminatory capacity for oesophageal dysfunction in systemic sclerosis (area
      under the curve, 95% confidence interval: 0.80, 0.70-0.89 and 0.92, 0.86-0.98,
      respectively). There is a clinically significant association between oesophageal
      dysmotility and high-resolution CT findings of oesophageal coronal dilatation.
      The evaluation of infra-aortic oesophageal coronal diameter can provide
      additional useful information about the functional and anatomic conditions of the
      oesophagus in systemic sclerosis.

PMID- 16885179
TI  - A qualitative study of factors influencing antimicrobial prescribing by non
      consultant hospital doctors.
AB  - OBJECTIVES: To determine the factors that influence non-consultant hospital
      doctors (NCHDs) in their decision to prescribe antimicrobial agents. METHODS: A
      qualitative study using semi-structured interviews centred on a life grid
      tracking the medical career of 22 NCHDs employed by a university teaching
      hospital in the west of Ireland. RESULTS: Early in their careers NCHD prescribing
      is based primarily on the immediate influence of more senior colleagues.
      Recollection of formalized undergraduate teaching and hospital guidelines are a
      very minor influence. As their career progressed and they exercise greater
      autonomy, personal experience becomes the major influence on prescribing
      decisions. Hospital guidelines are a minor influence. Participants consider that
      undergraduate teaching needs to be more practical and taught in a way that is
      easier to apply to on-ward situations and that hospital prescribing guidelines
      need to be presented in a 'user-friendly' format and adherence to the guidelines
      needs to be promoted. CONCLUSIONS: The key influences on antimicrobial
      prescribing by NCHDs are informal. New approaches are required to ensure that
      formal training and hospital guidelines on antimicrobial prescribing are more
      influential in shaping antimicrobial prescribing practice.

PMID- 16885180
TI  - Once-daily tobramycin in cystic fibrosis: better for clinical outcome than thrice
      daily tobramycin but more resistance development?
AB  - OBJECTIVES: Once-daily administration of aminoglycosides in cystic fibrosis (CF)
      patients is considered equally efficacious and potentially less nephrotoxic than
      dosing three times a day. However, the choice of the most suitable PK/PD index
      (C(max)/MIC versus AUC(24)/MIC) to ensure optimum clinical outcome in this
      patient population is not clear. PATIENTS AND METHODS: In a single-centre, open,
      randomized, controlled, non-blinded study 33 adult CF patients (20 females, 19-37
      years) were treated with intravenous tobramycin (10 mg/kg/day) for 14 days given
      either as single dose once a day (Q24; 17 patients) or divided into three equal
      doses every 8 h (Q8; 16 patients). Tobramycin serum concentrations and MICs for
      Pseudomonas aeruginosa were determined on days 1 and 14. The clinical outcome
      parameter, correlated to PK/PD indices, was the percentage predicted forced
      expiratory volume in 1 s (FEV(1)% pred.). RESULTS: FEV(1)% pred. improved
      significantly for both treatments. There was a log-linear relationship between
      C(max)/MIC and FEV(1)% pred. and AUC/MIC and FEV(1)% pred. for both treatments.
      For equal values of AUC24/MIC, however, Q24 treatment provided better improvement
      in lung function than Q8 dosing, whereas C(max)/MIC did not show any dosing
      interval dependence. A statistically significant increase was observed for MIC
      (day 1) versus MIC (day 14) for Q24 treatment, however, no such difference was
      observed for Q8 treatment. CONCLUSIONS: The most important PK/PD parameter for
      clinical outcome in CF patients was C(max)/MIC. Outcome prediction of AUC(24)/MIC
      was dependent on the regimen. The increase of P. aeruginosa resistance after once
      daily administration is linked to a long dosing interval. More and larger studies
      are needed to optimize the dosing regimen for maximum clinical outcome with
      minimum resistance development.

PMID- 16885181
TI  - Cationic lipids and surfactants as antifungal agents: mode of action.
AB  - OBJECTIVES: To determine the mechanism of antimicrobial action for cationic lipid
      dioctadecyldimethylammonium bromide (DODAB) and hexadecyltrimethylammonium
      bromide (CTAB) against Candida albicans. METHODS: Determination of DODAB or CTAB
      adsorption isotherms; cell viability; cell electrophoretic mobility (EM); and
      leakage of small phosphorylated compounds, proteins or DNA from fungus or
      haemoglobin from erythrocytes. RESULTS: High affinity isotherms for CTAB and
      DODAB adsorption onto fungus cells (10(8) cfu/mL) yield limiting adsorption at
      7.8 and 3.7 x 10(9) molecules per cell, respectively. Negatively charged C.
      albicans cells (10(6) cfu/mL) remain viable whereas positively charged ones die.
      At 0.3 mM CTAB or 0.01 mM DODAB, EM is zero and fungus viability is 50%. Cells
      start to die at submicellar CTAB concentrations and fungus lysis does not play a
      significant role in the mechanism of antifungal action. Over 0.1-10 mM CTAB or
      DODAB, there is no leakage of tested compounds from C. albicans cells despite the
      low cell viability. In contrast to the fungus, under isotonic conditions,
      cationic amphiphiles induce haemolysis over a range of low DODAB (>0.01 mM) and
      CTAB (>0.001 mM) concentrations. CONCLUSIONS: The critical phenomenon determining
      antifungal effect of cationic surfactants and lipids is not cell lysis but rather
      the change of cell surface charge from negative to positive.

PMID- 16885182
TI  - Safety and efficacy of routine postoperative ibuprofen for pain and disability
      related to ectopic bone formation after hip replacement surgery (HIPAID):
      randomised controlled trial.
AB  - OBJECTIVES: To determine the benefits and risks of a non-steroidal anti
      inflammatory drug (NSAID) as prophylaxis for ectopic bone formation in patients
      undergoing total hip replacement (or revision) surgery. DESIGN: Double blind
      randomised placebo controlled clinical trial, stratified by treatment site and
      surgery (primary or revision). SETTING: 20 orthopaedic surgery centres in
      Australia and New Zealand. PARTICIPANTS: 902 patients undergoing elective primary
      or revision total hip replacement surgery. INTERVENTION: 14 days' treatment with
      ibuprofen (1200 mg daily) or matching placebo started within 24 hours of surgery.
      MAIN OUTCOME MEASURES: Changes in self reported hip pain and physical function 6
      to 12 months after surgery (Western Ontario and McMaster University Arthritis
      index). RESULTS: There were no significant differences between the groups for
      improvements in hip pain (mean difference -0.1, 95% confidence interval -0.4 to
      0.2, P = 0.6) or physical function (-0.1, -0.4 to 0.2, P = 0.5), despite a
      decreased risk of ectopic bone formation (relative risk 0.69, 0.56 to 0.83)
      associated with ibuprofen. There was a significantly increased risk of major
      bleeding complications in the ibuprofen group during the admission period (2.09,
      1.00 to 4.39). CONCLUSIONS: These data do not support the use of routine
      prophylaxis with NSAIDs in patients undergoing total hip replacement surgery.
      TRIAL REGISTRATION: NCT00145730.

PMID- 16885183
TI  - Clinical features in a family with an R460H mutation in transforming growth
      factor beta receptor 2 gene.
AB  - OBJECTIVES: To describe the clinical findings and natural history in 22 carriers
      of an R460H mutation in the transforming growth factor beta receptor 2 gene
      (TGFbetaR2) from a five-generation kindred ascertained by familial aortic
      dissection. METHODS: 13 of the confirmed carriers were interviewed and examined,
      and information about the remaining carrier was obtained from medical records.
      Clinical information about deceased individuals was obtained, when possible, from
      postmortem reports, death certificates and medical records. RESULTS: There have
      been eight sudden deaths; the cause of death was aortic dissection in all six
      cases in which a postmortem examination was performed. Three individuals had
      undergone aortic replacement surgery. Dissection had occurred throughout the
      aorta, and in one case in the absence of aortic root dilatation. Subarachnoid
      haemorrhage, due to a ruptured berry aneurysm, had occurred in two individuals.
      Four gene carriers and one deceased family member who were investigated had
      tortuous cerebral blood vessels. One had tortuous vertebral arteries, two had
      tortuous carotid arteries and one a tortuous abdominal aorta. Two individuals
      were found to have a brachiocephalic artery aneurysm and a subclavian artery
      aneurysm, respectively. CONCLUSIONS: Despite the predisposition to aortic
      dilatation and dissection, individuals did not frequently manifest the skeletal
      features of Marfan syndrome, with the exception of joint hypermobility. No one
      individual had ocular lens dislocation. Striae and herniae were common. There was
      some overlap with Ehlers-Danlos syndrome type 4, OMIM 130050, with soft
      translucent skin, which is easily bruised. Other features were arthralgia,
      migraine and a tendency to fatigue easily, varicose veins and prominent skin
      striae. This family provides further evidence that mutations in TGFbetaR2 cause a
      distinct syndrome that needs to be distinguished from Marfan syndrome to direct
      investigation and management of patients and shows the natural history, spectrum
      of clinical features and variable penetrance of this newly recognised condition.

PMID- 16885184
TI  - Commercial sex venues: a closer look at their impact on the syphilis and HIV
      epidemics among men who have sex with men.
AB  - OBJECTIVE: To provide insight into the role of commercial sex venues in the
      spread of syphilis and HIV among men who have sex with men (MSM). STUDY: A cross
      sectional study of 1351 MSM who were diagnosed with early syphilis who did and
      did not encounter sexual partners at commercial sex venues. RESULTS: Overall, 26%
      MSM diagnosed with syphilis had sexual encounters at commercial sex venues. Of
      these, 74% were HIV positive, 94% reported anonymous sex, and 66% did not use a
      condom. Compared to those who did not have a sexual encounter at these venues,
      they were twice as likely to be HIV positive (OR = 1.91, 95% CI 1.36 to 2.68),
      six times more likely to have anonymous sex (OR = 6.18, 95% CI 3.37 to 11.32),
      twice as likely not to use condom (OR = 2.02, 95% CI 1.71 to 2.38), and twice as
      likely to use non-injecting drugs (OR = 1.65, 95% CI 1.21 to 2.37). CONCLUSIONS:
      MSM diagnosed with syphilis who frequent commercial sex venues are engaging in
      high risk behaviours for syphilis and HIV transmission and acquisition. Thus
      commercial sex venues are one of the focal points of syphilis and HIV
      transmission and acquisition.

PMID- 16885185
TI  - Age differences in central and peripheral intraocular pressure using a rebound
      tonometer.
AB  - AIM: To evaluate the influence of age on the measurements and relationships among
      central and peripheral intraocular pressure (IOP) readings taken with a rebound
      tonometer. METHODS: The IOPs were measured using the ICare rebound tonometer on
      the right eyes of 217 patients (88 men and 129 women) aged 18-85 years (mean 45.9
      (SD 19.8) years), at the centre and at 2 mm from the nasal and temporal limbus
      along the horizontal meridian. Three age groups were established: young (< or =30
      years old; n = 75), middle aged (31-60 years old; n = 77) and old patients (>60
      years old; n = 65). RESULTS: A high correlation was found between the central and
      peripheral IOP readings, with the central readings being higher than the
      peripheral ones. Higher IOP values for the central location were found in the
      younger patients. Older patients had significantly lower temporal IOP readings
      than those for the remaining two groups (p<0.001), whereas no significant
      differences were found among groups when IOP was measured at the central and
      nasal locations. A significant decrease was observed in the nasal and temporal
      IOP readings as the age increased (p = 0.011 and 0.006, respectively).
      CONCLUSION: Older patients had lower IOP values than the middle-aged and younger
      patients in the temporal peripheral location. A negative correlation was found
      between age and IOP by rebound tonometry in the corneal periphery but not in its
      centre.

PMID- 16885186
TI  - Retrobulbar blood flow in patients with cataract.
AB  - OBJECTIVE: To investigate retrobulbar haemodynamics in patients with cataract.
      SUBJECTS AND METHODS: Colour Doppler imaging of the ophthalmic artery was carried
      out on the eye scheduled for surgery in 30 patients with cataract and in one
      randomly selected eye of 100 healthy controls. The peak systolic velocity, mean
      velocity, end diastolic velocity and resistivity index in the ophthalmic artery
      were computed and adjusted for the influence of age and mean arterial pressure.
      Cataract type was recorded and lens opacity was measured with an opacity
      lensmeter. Odds ratio (OR) for cataract was analysed in a logistic regression
      model, depending on the adjusted blood-flow parameters, age and smoking status.
      RESULTS: The mean (SD) age was 45.5 (17.7) and 67.6 (5.8) years in controls and
      patients with cataract, respectively (p<0.001). The female to male ratio was
      54:46 and 13:17, respectively (p = 0.41). Significant predictors of cataract in a
      forward stepwise logistic regression analysis were age (OR = 1.194; 95%
      confidence interval (CI) = 1.103 to 1.292; p<0.001), smoking status (OR = 14.119;
      95% CI = 2.753 to 72.398; p = 0.002) and mean blood-flow velocity in the
      ophthalmic artery (OR = 0.731; 95% CI = 0.607 to 0.881; p = 0.001). Adjusted mean
      velocity was significantly lower in patients with cataract, even when only age
      matched (age >55 years) non-smokers (31 controls, 19 patients with cataract) were
      considered (p = 0.003). Lens opacity and the type of cataract had no influence on
      the present findings. CONCLUSION: High mean velocity in the ophthalmic artery may
      be associated with a reduced risk of cataract.

PMID- 16885187
TI  - Distance stereoacuity in intermittent exotropia.
AB  - BACKGROUND: Studies of distance stereoacuity in intermittent exotropia suggest
      that normal stereoacuity corresponds to good control of the deviation and that
      reduced or negative stereoacuity signifies poorer control. AIM: : To evaluate
      distance stereoacuity in intermittent exotropia using the Frisby Davis Distance
      stereo test (FD2). METHODS: Children with intermittent exotropia where the near
      angle was less than or equal to distance were eligible for recruitment.
      Standardised prospective data collection included FD2 distance stereoacuity. This
      was a longitudinal study in which outcomes are reported for baseline, last follow
      up (> or =6 months before any surgery) or preoperative and last postoperative
      visits for those undergoing surgery. RESULTS: 110 children with intermittent
      exotropia had FD2 stereoacuity tested at baseline: 70 comprehended the test. Mean
      (standard deviation (SD)) age was 4.6 (1.7) years (range 2-10 years). 41/70 (59%)
      showed positive responses: mean (SD) stereoacuity 30 (12) s of arc. The mean
      follow-up period before any surgery was 13 months (range 6-27 months). At follow
      up, mean (SD) stereoacuity was 24 (11) s of arc. Preoperative and postoperative
      stereoacuity were not significantly different from those not undergoing surgery.
      CONCLUSION: This study was the first to report distance stereoacuity in
      intermittent exotropia using the FD2 stereo test: patients with intermittent
      exotropia can achieve normal levels of distance stereoacuity, but a considerable
      proportion, despite comprehending, showed a negative response. This suggests that
      using the FD2, distance stereoacuity in intermittent exotropia is either absent
      or normal rather than reduced. Possible reasons for this and its implications are
      discussed.

PMID- 16885189
TI  - The role of scanning laser polarimetry using the GDx variable corneal compensator
      in the management of glaucoma suspects.
AB  - AIM: To determine the role of scanning laser polarimetry using the GDx variable
      corneal compensator (VCC) in the management of glaucoma suspects. METHODS: Over a
      12-month period, 43 of 447 (9.6%) patients referred to a glaucoma screening
      clinic were classified as "glaucoma suspects" when it was not possible to
      categorise the optic disc appearance and visual fields as definitely glaucomatous
      or definitely normal. Of these patients, 39 underwent a full ophthalmic review,
      including assessment of the visual fields and analysis of the retinal nerve fibre
      layer with the GDx VCC. RESULTS: After the review, 17 of 39 (43.6%) patients were
      discharged because of normal GDx VCC results. The remaining 22 of 39 (56.4%) were
      considered to be at risk of developing progressive glaucoma, and further follow
      up in the hospital eye service was recommended. 3 (7.7%) patients received
      treatment. Of the 22 patients, 12 were considered to have pre-perimetric normal
      tension glaucoma, 7 normal tension glaucoma and 1 primary open-angle glaucoma
      (POAG). In 19 of these patients, abnormal GDx VCC results were found,
      particularly inter-eye asymmetry in the nerve fibre layer thickness. However, in
      2 of 39 (5.1%) patients the GDx VCC was normal, despite the presence of a
      neuroretinal rim defect in the optic disc with corresponding visual field loss,
      and in 1 patient with POAG. CONCLUSIONS: Scanning laser polarimetry using the GDx
      VCC is an important tool in defining the management strategies of glaucoma
      suspects. In screening for glaucoma, however, GDx VCC results should not be used
      in isolation, but in conjunction with conventional methods of optic disc and
      visual field assessment.

PMID- 16885188
TI  - The role of the Met98Lys optineurin variant in inherited optic nerve diseases.
AB  - AIMS: To investigate the role of the common OPTN Met98Lys variant as a risk
      allele in open-angle glaucoma (OAG), autosomal dominant optic atrophy (ADOA) and
      Leber's hereditary optic neuropathy (LHON). METHODS: The presence of the Met98Lys
      variant was determined in a total of 498 (128 with normal-tension glaucoma (NTG))
      patients with OAG, 29 patients who had myocilin-related OAG, 101 patients from
      ADOA pedigrees, 157 patients from LHON pedigrees and 218 examined OAG age-matched
      normal controls. RESULTS: 17 of 218 (7.8%) controls had the Met98Lys variant. 28
      (5.6%) patients with OAG were Met98Lys positive. More Met98Lys carriers were
      found in the NTG group than in the high-tension glaucoma (HTG) group (p = 0.033).
      However, no significant difference was observed between the NTG and control
      cohorts (p = 0.609). Two MYOC mutation carriers were found to have the variant.
      The variant was found in 1 of 10 pedigrees with ADOA and in 8 of 35 pedigrees
      with LHON. CONCLUSION: Data from this study do not support a strong role for the
      OPTN Met98Lys variant in glaucoma, ADOA or LHON. However, a weak association was
      observed of the variant with NTG compared with that with HTG. Meta-analysis of
      all published data on the variant and glaucoma confirmed that the association,
      although weak, is highly statistically significant in the cohort with glaucoma
      versus controls.

PMID- 16885190
TI  - Knowledge of visual experience during cataract surgery under local anaesthesia: a
      nationwide survey of UK ophthalmologists.
AB  - AIM: To evaluate the knowledge and practices of UK ophthalmologists regarding
      patients' subjective visual experience during cataract surgery under local
      anaesthesia. METHODS: A nationwide postal survey was conducted on UK
      ophthalmologists using a standardised questionnaire. RESULTS: The proportion of
      surgeons who operated under regional anaesthesia who thought that patients could
      experience the following visual sensations were: no light perception (54%); light
      perception (95%); one or more colours (93%); flashes of light (81%); movement
      (87%); instruments (61%); surgeon's hands or fingers (53%); surgeon (43%); and
      changes in light brightness (88%). Fifty-eight per cent of them thought that
      patients might be frightened by this, and 77% thought that preoperative
      counselling could help alleviate this fear. The proportion of surgeons who
      operated under topical anaesthesia who thought that patients could experience the
      following visual sensations were: no light perception (10%); light perception
      (94%); one or more colours (97%); flashes of light (86%); movement (96%);
      instruments (81%); surgeon's hands or fingers (65%); surgeon (51%); changes in
      light brightness (95%). Fifty-nine per cent of them thought that patients might
      be frightened by this, and 80% thought that preoperative counselling could help
      alleviate this fear. CONCLUSION: Most UK surgeons believed that during cataract
      surgery under local anaesthesia, patients might experience various visual
      sensations which could cause fear and that such fear could be alleviated by
      preoperative counselling.

PMID- 16885191
TI  - Intravitreal triamcinolone and laser photocoagulation for retinal angiomatous
      proliferation.
AB  - BACKGROUND: Recently, the entity of retinal angiomatous proliferation (RAP) as a
      subtype of exudative age-related macular degeneration was described, but no
      treatment options have been established as yet. The only two therapeutic
      modalities being discussed are surgical lysis of the feeding arteriole and
      draining venule, and the use of photodynamic therapy combined with intravitreal
      triamcinolone injection. AIM: To examine focal laser treatment of early
      extrafoveal intraretinal neovascularisation of RAP. METHODS: Prospective case
      series. We included 13 consecutive patients with an extrafoveal RAP stage I
      lesion. All patients underwent a complete ophthalmic examination, including
      fluorescein angiography and optical coherence tomography (OCT) III before
      treatment and at 2 weeks, 1, 2 and 4 months afterwards. In cases with marked
      macular oedema (>350 mum retinal thickening in OCT III, r = 12), intravitreal
      injection of 4 mg triamcinolone was given before focal laser treatment to reduce
      the oedema. RESULTS: This case series indicates anatomical improvement or
      stabilisation in patients with an extrafoveal RAP lesion after treatment. Initial
      visual acuity ranged from 0.1 to 0.6 on the Snellen chart. By calculating
      logarithmic values, visual acuity was seen to be improved in five cases (2 to 5
      log lines), deteriorated in four cases (-2 to 5 log lines) and stabilised in four
      cases (-1 to +1 log line change). Exudation on fluorescein angiography was
      stopped in 11 cases. CONCLUSIONS: This preliminary case series suggests laser
      photocoagulation combined with prior intravitreal triamcinolone injection as a
      viable treatment option for RAP stage I. In cases with marked macular oedema,
      intravitreal triamcinolone injection improved visual acuity. For long-term
      stabilisation, additional laser treatment is mandatory. These preliminary results
      warrant a more detailed prospective clinical trial.

PMID- 16885192
TI  - Effect of refractive surgery on binocular vision and ocular alignment in patients
      with manifest or intermittent strabismus.
AB  - OBJECTIVE: To evaluate the effect of refractive surgery on binocular vision and
      ocular alignment in patients with manifest or intermittent strabismus, with or
      without vertical component. SETTING: University Hospital Antwerp, Edegem,
      Belgium. PATIENTS AND METHODS: 13 patients (22 eyes) with strabismus underwent
      refractive surgery. Five of these patients presented with an esotropia and four
      of them with a small vertical deviation. Five patients had a manifest exotropia,
      of whom two presented with a small vertical deviation. Two patients had an
      intermittent exotropia with binocular vision, of whom one patient had a vertical
      deviation. One patient had a hypertropia with a dissociated vertical deviation.
      RESULTS: Ocular alignment and binocular function remained unchanged
      postoperatively in all except two patients with high anisometropia who
      experienced an improvement in binocular function. In these patients, the
      preoperative manifest deviation became intermittent or latent after surgery,
      allowing fusion and stereopsis. Vertical deviation was found preoperatively in 8
      of the 13 patients. This vertical deviation remained unchanged postoperatively,
      but improved in one patient with anisometropia. CONCLUSION: Preoperative
      intermittent or manifest strabismus is not a contraindication for refractive
      surgery provided some specific recommendations are taken into account, such as an
      adequate preoperative orthoptic examination and aiming at emmetropia for both
      eyes.

PMID- 16885193
TI  - Evolutionary insights into the high worldwide prevalence of MBL2 deficiency
      alleles.
AB  - Human mannose-binding lectin (MBL) is a member of the collectin protein family
      that binds a broad range of microorganisms and activates the lectin-complement
      pathway of innate immunity. Common alleles of MBL2 disrupt the MBL protein or
      modulate the amount of protein produced, resulting in MBL deficiency. The
      clinical manifestations of MBL deficiency have been extensively studied but the
      actual role of this lectin in immunity to infection remains a matter of strong
      debate. MBL is commonly thought to play a key role in protective immunity,
      because MBL deficiency has been associated with an increase in susceptibility to
      infectious diseases. However, the high worldwide prevalence of multiple MBL2
      deficiency or low-producing alleles suggests the converse that MBL deficiency
      confers protection. To explore the underlying forces accounting for the high
      worldwide prevalence of MBL2 deficiency alleles, we characterized genetic
      diversity in and around the MBL2 genomic region in 1166 chromosomes from 24
      worldwide populations. Our results clearly demonstrate that the patterns of MBL2
      variation are compatible with neutral evolution, as opposed to negative, positive
      or balanced natural selection. The high worldwide frequencies of MBL2 alleles
      associated with the production of little or no protein therefore result
      exclusively from human migration and genetic drift. The evolutionary neutrality
      of MBL2 strongly supports the notion that MBL2 variation does not have strong
      effects on population fitness, suggesting, therefore, that this lectin is largely
      redundant in host human defences.

PMID- 16885194
TI  - Pals1/Mpp5 is required for correct localization of Crb1 at the subapical region
      in polarized Muller glia cells.
AB  - Mutations in the human Crumbs homologue-1 (CRB1) gene cause retinal diseases
      including Leber's congenital amaurosis (LCA) and retinitis pigmentosa type 12.
      The CRB1 transmembrane protein localizes at a subapical region (SAR) above
      intercellular adherens junctions between photoreceptor and Muller glia (MG)
      cells. We demonstrate that the Crb1-/- phenotype, as shown in Crb1-/- mice, is
      accelerated and intensified in primary retina cultures. Immuno-electron
      microscopy showed strong Crb1 immunoreactivity at the SAR in MG cells but barely
      in photoreceptor cells, whereas Crb2, Crb3, Patj, Pals1 and Mupp1 were present in
      both cell types. Human CRB1, introduced in MG cells in Crb1-/- primary retinas,
      was targeted to the SAR. RNA interference-induced silencing of the Crb1
      interacting-protein Pals1 (protein associated with Lin7; Mpp5) in MG cells
      resulted in loss of Crb1, Crb2, Mupp1 and Veli3 protein localization and partial
      loss of Crb3. We conclude that Pals1 is required for correct localization of Crb
      family members and its interactors at the SAR of polarized MG cells.

PMID- 16885195
TI  - Expression of human glutathione S-transferase P1 confers resistance to
      benzo[a]pyrene or benzo[a]pyrene-7,8-dihydrodiol mutagenesis, macromolecular
      alkylation and formation of stable N2-Gua-BPDE adducts in stably transfected
      V79MZ cells co-expressing hCYP1A1.
AB  - Transgenic cell lines were constructed to study dynamic competition between
      activation versus detoxification of benzo[a]pyrene (B[a]P) and its metabolites.
      Transfected V79MZ cells expressing human cytochrome P4501A1 (hCYP1A1) alone, or
      expressing hCYP1A1 in combination with human glutathione S-transferase P1
      (hGSTP1), were used to determine how effectively GST protects against
      macromolecular damage or mutagenicity of B[a]P or its enantiomeric dihydrodiol
      metabolites (+)-benzo[a]pyrene-7,8-dihydrodiol [(+)B[a]P-7,8-diol] and (-)
      benzo[a]pyrene-7,8-dihydrodiol [(-)-B[a]P-7,8-diol]. Mutagenicity of B[a]P at the
      hprt locus was dose- and time-dependent in cells that expressed hCYP1A1.
      Mutagenicity was reduced in cells further modified to co-express hGSTP1. Dose
      response and time-course studies indicated that mutagenicity was reduced up to 3
      fold by hGSTP1 expression, compared with cells expressing hCYP1A1 alone.
      Mutagenicity induced by the B[a]P 7,8-dihydrodiols was also dose-dependent, and
      was reduced 2- to 5-fold by hGSTP1. Expression of hGSTP1 reduced B[a]P adducts in
      total cellular macromolecules by 3.8-fold, which correlated with the reduction in
      B[a]P mutagenicity and with reduction in the formation of the proximate
      metabolite B[a]P 7,8-dihydrodiols from B[a]P. However, measurement of total B[a]P
      metabolites bound to DNA isolated from cells incubated with [3H]-B[a]P revealed
      only 12, 33 and 24% reduction at 12, 24 and 48 h, respectively, by GSTP1
      expression. Nevertheless, (32)P-post-labeling analysis demonstrated nearly total
      prevention of the known B[a]P-DNA adduct, N2-guanine-benzo[a]pyrene-7,8-diol-9,10
      epoxide (BPDE), in cells co-expressing hGSTP1. This adduct, thought to be the
      most mutagenic of the stable B[a]P adducts, accounts for 15% or less of the total
      DNA adducts observed. These results indicate that the reduction in hCYP1A1
      mediated B[a]P mutagenesis by hGSTP1 is probably largely due to prevention of the
      N2-guanine-BPDE adduct. However, the significant fraction (30-40%) of this
      mutagenesis and the majority of the total DNA binding that are not prevented
      together suggest formation by hCYP1A1 of a subset of mutagenic metabolites of
      B[a]P that are not effectively detoxified by hGSTP1.

PMID- 16885196
TI  - Polymorphisms in Th1-type cell-mediated response genes and risk of gastric
      cancer.
AB  - Helicobacter pylori infection, the dominant risk factor for gastric cancers, has
      been shown to elicit T helper type 1 (Th1) polarized immunological responses. We
      conducted a population-based study of 305 gastric cancer cases and 427 age- and
      gender-matched controls in Warsaw, Poland, to evaluate the association with
      several variants in genes responsible for Th1-cell-mediated response. Genotyping
      was performed on genomic DNA by TaqMan(TM) assays to determine TNFA (-308 G>A, 
      417 G>A, -555 G>A, -1036 C>T, -1042 C>A, -1210 T>C), IL1A (-889 C>T), IFNGR2 (Ex7
      128 T>C, Ex2-34 C>G and Ex2-16 A>G) and IL12A (IVS2-798 T>A, IVS2-701 C>A and
      Ex7+277 G>A) polymorphisms. We used unconditional logistic regression to estimate
      odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for sex, age,
      education and smoking status. Out of six single nucleotide polymorphisms (SNPs)
      tested in TNFA, gastric cancer risk was significantly associated with the TNFA (
      308 G>A) polymorphism, with ORs of 1.4 (95% CI: 1.0-2.0) for the G/A and 2.5 (95%
      CI: 1.3-4.9) for the A/A genotype carriers, when compared with the more frequent
      genotype (G/G) (P-trend < 0.001). Among the three tested SNPs in the IFNGR2 gene,
      only the Ex7-128C>T polymorphism was associated with increased risk, with ORs of
      1.5 (95% CI: 1.0-2.3) for T/C and 1.7 (95% CI: 1.1-2.7) for C/C carriers when
      compared with T/T carriers (P-trend = 0.01). Subjects carrying both IFNGR2 Ex7
      128 C/C and TNFA -308 A/A genotypes had the highest risk (OR = 5.5, 95% CI: 1.5
      19.4), although the interaction was not statistically significant. IL1A (-889
      C>T) and the three examined IL12A variants were unrelated to gastric cancer risk.
      Our findings suggest that two Th1-related polymorphisms (TNFA -308 A>G and IFNGR2
      Ex7-128 C>T) may increase the risk of gastric cancer.

PMID- 16885197
TI  - Apc mutation induces resistance of colonic cells to lipoperoxide-triggered
      apoptosis induced by faecal water from haem-fed rats.
AB  - Recent epidemiological studies suggest that high meat intake is associated with
      promotion of colon cancer linked with haem-iron intake. We previously reported
      that dietary haem, in the form of either haemoglobin or meat, promotes
      precancerous lesions in the colon of rats given a low-calcium diet. The mechanism
      of promotion by haem is not known, but is associated with increased lipid
      peroxidation in faecal water and strong cytotoxic activity of faecal water on a
      cancerous mouse colonic epithelial cell line. To better understand the
      involvement of faecal water components of haem-fed rats in colon-cancer
      promotion, we explored the effect of faecal water on normal [adenomatous
      polyposis coli (Apc)+/+] or premalignant cells (Apc-/+). Further, we tested if
      this effect was correlated to lipoperoxidation and 4-hydroxynonenal (HNE). We
      show here for the first time that heterozygote Apc mutation represents a strong
      selective advantage, via resistance to apoptosis induction (caspase 3 pathway),
      for colonic cells exposed to a haem-iron-induced lipoperoxidation. The fact that
      HNE treatment of the cells provoked the same effects as the faecal water of rats
      fed the haem-rich diet suggests that this compound triggers apoptosis in those
      cells. We propose that this mechanism could be involved in the promotion of colon
      carcinogenesis by haem in vivo.

PMID- 16885198
TI  - Pre-clinical investigations of physical activity and cancer: a brief review and
      analysis.
AB  - There is substantial evidence that physical inactivity is an important risk
      factor for a number of chronic diseases, including cancer. As consequences of
      physical inactivity on cancer risk and treatment efficacy surface, there is
      increasing interest in determining the benefits of a physically active lifestyle
      and of exercise as a component of that lifestyle. In the cancer research field,
      the spectrum of research activities includes pre-clinical studies and clinical
      and population-based interventions; of these approaches, pre-clinical experiments
      combining animal cancer models with physical activity (PA) have been
      underutilized. Clarifying the amounts and types of PA that inhibit carcinogenesis
      is best done in animals, where mechanistic inquiry and biomarker evaluation of
      the protected state can be carried out in a more favorable environment than in
      clinical populations. The expertise required to integrate models for
      investigating PA with those used to study carcinogenesis is not trivial, but
      mastery of these models is likely to result in highly translatable pre-clinical
      findings that advance this important field of investigation. This brief review
      and analysis is intended to focus attention on the issues and opportunities
      associated with the pre-clinical investigations of PA and cancer.

PMID- 16885199
TI  - Prevention of mouse lung tumors and modulation of DNA methylation by combined
      treatment with budesonide and R115777 (Zarnestra MT).
AB  - Budesonide (an anti-inflammatory glucocorticoid), R115777 (a farnesyl transferase
      inhibitor, Zarnestra, Tipifarnib) or combinations of them were evaluated for
      prevention of lung tumors and for modulation of DNA methylation in tumors. Lung
      tumors were induced by vinyl carbamate in female strain A mice. One week later,
      mice received 60 or 100 mg/kg R115777 by oral gavage and 5 days/week, 0.8 or 1.6
      mg/kg of budesonide in their diet, or their combined treatment until killed at
      20, 28 and 36 weeks after administering the vinyl carbamate. Other mice were
      administered the drugs for 2 weeks before killing at Week 20. At Week 20, the
      rank order for prevention of lung tumors was the combined treatment > budesonide
      > R115777. At later killings, R115777 was no longer effective, whereas budesonide
      and the combinations continued to prevent tumors, albeit at a reduced efficacy.
      DNA hypomethylation in lung tumors was prevented by treatment with R115777,
      budesonide and the combinations. When administered starting at Week 18 to tumor
      bearing mice, the drugs reversed DNA hypomethylation in the tumors. In summary,
      combined treatment with budesonide and R115777 produced the following results:
      (i) it was more efficacious in preventing lung tumors than the individual drugs;
      and (ii) it prevented and reversed DNA hypomethylation in lung tumors. These
      results support the combined use of budesonide and R115777 in prevention of lung
      tumors and suggest that reversal of DNA hypomethylation in lung tumors would be
      useful as a surrogate end-point biomarker for prevention.

PMID- 16885201
TI  - ACC/AHA/ESC 2006 guidelines for the management of patients with atrial
      fibrillation-executive summary: a report of the American College of
      Cardiology/American Heart Association Task Force on Practice Guidelines and the
      European Society of Cardiology Committee for Practice Guidelines (Writing
      Committee to Revise the 2001 Guidelines for the Management of Patients with
      Atrial Fibrillation).

PMID- 16885202
TI  - Smoking status moderates the contribution of social-cognitive and environmental
      determinants to adolescents' smoking intentions.
AB  - In this study, it was tested whether attitudes, self-efficacy, social influences
      and the perception of the school and home environments had different associations
      with intentions for adolescent non-smokers, occasional smokers and daily smokers.
      A regression model allowing for separate slopes of social-cognitive and
      environment variables accounted for 72% of the variation in intentions. For non
      smokers, ease of refusing to smoke (beta = -0.06) and social influences favouring
      smoking (beta = 0.05) were linked to intentions. Occasional and daily smokers'
      intentions were associated with health consequences (beta = -0.05 and beta = 
      0.06, respectively) and ease of smoking/buying cigarettes (beta = 0.05 and beta =
      0.24, respectively). Social influences favouring smoking (beta = 0.10) were also
      associated with intentions in daily smokers. In an extended model for current
      smokers (adjusted R(2) = 0.45), context-cued nicotine cravings (beta = 0.27) were
      linked to daily smokers', but not occasional smokers' intentions. The results
      suggest that motivating adolescents to abstain from or to quit smoking implies
      working on different combinations of determinants in non-smokers, occasional
      smokers and daily smokers. Interventions for daily smokers should supplement
      motivational techniques with stratagems that allow smokers to reduce the number
      of cravings they experience in specific contexts.

PMID- 16885203
TI  - Testicular self-examination: a test of the health belief model and the theory of
      planned behaviour.
AB  - The aim of this study was to test the utility and efficiency of the theory of
      planned behaviour (TPB) and the health belief model (HBM) in predicting
      testicular self-examination (TSE) behaviour. A questionnaire was administered to
      an opportunistic sample of 195 undergraduates aged 18-39 years. Structural
      equation modelling indicated that, on the basis of all the fit indices, the TPB
      model was the better model, however, the quality of the models was very similar.
      The TPB explained 50% of the variance in intention and 22% in behaviour while the
      HBM (with self-efficacy) accounted for 56 and 21%, respectively. Self-efficacy
      was the most important predictor of TSE behavioural intention across both models.
      These findings contribute to the growing literature on the testing of multiple
      models in the health psychology domain.

PMID- 16885204
TI  - Time-frequency intracranial source localization of feedback-related EEG activity
      in hypothesis testing.
AB  - The neural correlates of the response to performance feedback have been the
      object of numerous neuroimaging studies. However, the precise timing and
      functional meaning of the resulting activations are poorly understood. We studied
      the electroencephalographic response time locked to positive and negative
      performance feedback in a hypothesis testing paradigm. The signal was convoluted
      with a family of complex wavelets. Intracranial sources of activity at various
      narrow-band frequencies were estimated in the 100- to 400-ms time window
      following feedback onset. Positive and negative feedback were associated to 1)
      early parahippocampo-cingular sources of alpha oscillations, more posteriorly
      located and long lasting for negative feedback and to 2) late partially
      overlapping neural circuits comprising regions in prefrontal, cingular, and
      temporal cortices but operating at feedback-specific latencies and frequencies.
      The results were interpreted in the light of neurophysiological models of
      feedback and were used to discuss methodological issues in the study of high
      level cognitive functions, including reasoning and decision making.

PMID- 16885205
TI  - Schizophrenia patients with cognitive deficits: factors associated with costs.
AB  - Cognitive deficits in people with schizophrenia are associated with poor
      functioning and lower quality of life. Because few studies have examined their
      relationship with service use or costs, it is unclear whether effective cognitive
      remediation interventions have potential for economic impacts. This study
      examined associations between cognition and costs among people with
      schizophrenia. Baseline data collected between 1999 and 2002 from a randomized
      controlled trial of cognitive remediation therapy were analyzed. A total of 85
      participants were recruited from a London mental health trust if they had a
      diagnosis of schizophrenia, evidence of cognitive/social functioning
      difficulties, and at least 1 year since first contact with psychiatric services.
      Cognition levels, social functioning, symptoms, sociodemographic characteristics,
      and retrospective use of health/social care and other resources were measured.
      Average public sector costs were estimated to be 15 078 pounds(23 824 dollars)
      for a 6-month period. Associations between health/social care costs and type and
      severity of cognition were examined using structural equation models. No
      significant relationships were found between cognition and costs in a model based
      on 3 independent constituent components of cognition (cognitive shifting, verbal
      working memory, and response inhibition), although a model with covarying
      cognition components fitted the observed data well. A model with cognition as a
      single construct both fitted well and showed a significant relationship. In
      people with schizophrenia and severe cognitive impairment, improvements in either
      overall cognition or specific cognitive components may impact on costs. Further
      investigation in larger samples is needed to confirm this finding and to explore
      its generalizability to those with less severe deficits.

PMID- 16885206
TI  - Cognitive, emotional, and social processes in psychosis: refining cognitive
      behavioral therapy for persistent positive symptoms.
AB  - Psychosis used to be thought of as essentially a biological condition unamenable
      to psychological interventions. However, more recent research has shown that
      positive symptoms such as delusions and hallucinations are on a continuum with
      normality and therefore might also be susceptible to adaptations of the cognitive
      behavioral therapies found useful for anxiety and depression. In the context of a
      model of cognitive, emotional, and social processes in psychosis, the latest
      evidence for the putative psychological mechanisms that elicit and maintain
      symptoms is reviewed. There is now good support for emotional processes in
      psychosis, for the role of cognitive processes including reasoning biases, for
      the central role of appraisal, and for the effects of the social environment,
      including stress and trauma. We have also used virtual environments to test our
      hypotheses. These developments have improved our understanding of symptom
      dimensions such as distress and conviction and also provide a rationale for
      interventions, which have some evidence of efficacy. Therapeutic approaches are
      described as follows: a collaborative therapeutic relationship, managing
      dysphoria, helping service users reappraise their beliefs to reduce distress,
      working on negative schemas, managing and reducing stressful environments if
      possible, compensating for reasoning biases by using disconfirmation strategies,
      and considering the full range of evidence in order to reduce high conviction.
      Theoretical ideas supported by experimental evidence can inform the development
      of cognitive behavior therapy for persistent positive symptoms of psychosis.

PMID- 16885207
TI  - Recent advances in social skills training for schizophrenia.
AB  - Social skills training consists of learning activities utilizing behavioral
      techniques that enable persons with schizophrenia and other disabling mental
      disorders to acquire interpersonal disease management and independent living
      skills for improved functioning in their communities. A large and growing body of
      research supports the efficacy and effectiveness of social skills training for
      schizophrenia. When the type and frequency of training is linked to the phase of
      the disorder, patients can learn and retain a wide variety of social and
      independent living skills. Generalization of the skills for use in everyday life
      occurs when patients are provided with opportunities, encouragement, and
      reinforcement for practicing the skills in relevant situations. Recent advances
      in skills training include special adaptations and applications for improved
      generalization of training into the community, short-term stays in psychiatric
      inpatient units, dually diagnosed substance abusing mentally ill, minority
      groups, amplifying supported employment, treatment refractory schizophrenia,
      older adults, overcoming cognitive deficits, and negative symptoms as well as the
      inclusion of social skills training as part of multidimensional treatment and
      rehabilitation programs.

PMID- 16885208
TI  - Adenylyl cyclase 6 overexpression decreases the permeability of endothelial
      monolayers via preferential enhancement of prostacyclin receptor function.
AB  - Overexpression of adenylyl cyclase (AC) has been proposed as a potential gene
      therapy strategy to increase cAMP formation in cardiomyocytes and cardiac
      function in vivo. The impact of AC overexpression on endothelial cells, which
      will be traversed by genes delivered in vivo, has not been examined. Hence, the
      goal of the current study was to determine the consequence of AC overexpression
      on vascular endothelial cells in terms of G-protein-coupled receptor (GPCR)
      signaling and endothelial barrier function. We demonstrate that adenoviral
      mediated gene transfer of AC6 in human umbilical vein endothelial cells
      preferentially enhances prostacyclin receptor (versus other GPCR)-stimulated cAMP
      synthesis and, in parallel, inhibits thrombin-stimulated increases in endothelial
      cell barrier function. Using multiple strategies, including prostacyclin receptor
      targeted small interfering RNA, we identify that the enhancement of endothelial
      barrier function by AC6 overexpression is dependent on an autocrine/paracrine
      feedback pathway involving the release of prostacyclin and activation of
      prostacyclin receptors. AC6 overexpression in endothelial cells may have use as a
      means to enhance prostacyclin function and reduce endothelial barrier
      permeability.

PMID- 16885209
TI  - An inner pore residue (Asn406) in the Nav1.5 channel controls slow inactivation
      and enhances mibefradil block to T-type Ca2+ channel levels.
AB  - Mibefradil is a tetralol derivative once marketed to treat hyper-tension. Its
      primary target is the T-type Ca(2+) channel (IC(50), approximately 0.1-0.2
      microM), but it also blocks Na(+),K(+),Cl(-), and other Ca(2+) channels at higher
      concentrations. We have recently reported state-dependent mibefradil block of
      Na(+) channels in which apparent affinity was enhanced when channels were
      recruited to slow-inactivated conformations. The structural determinants
      controlling mibefradil block have not been identified, although evidence suggests
      involvement of regions near or within the inner pore. We tested whether
      mibefradil interacts with the local anesthetic (LA) binding site, which includes
      residues in the S6 segments of domains (D) I, III, and IV. Mutagenesis of DIII S6
      and DIVS6 did not reveal critical binding determinants. Substitution of Asn406 in
      DI S6 of cardiac Na(v)1.5, however, altered affinity in a manner dependent on the
      identity of the substituting residue. Replacing Asn406 with a phenylalanine or a
      cysteine increased affinity by 4- and 7-fold, respectively, thus conferring T
      type Ca(2+) channel-like mibefradil sensitivity to the Na(+) channel. A series of
      other substitutions that varied in size, charge, and hydrophobicity had minimal
      effects on mibefradil block, but all mutations dramatically altered the magnitude
      and voltage-dependence of slow inactivation, consistent with data in other
      isoforms. Channels did not slow-inactivate, however, at the voltages used to
      assay mibefradil block, supporting the idea that Asn406 lies within or near the
      mibefradil binding site.

PMID- 16885210
TI  - Magnetic resonance imaging with an optical atomic magnetometer.
AB  - We report an approach for the detection of magnetic resonance imaging without
      superconducting magnets and cryogenics: optical atomic magnetometry. This
      technique possesses a high sensitivity independent of the strength of the static
      magnetic field, extending the applicability of magnetic resonance imaging to low
      magnetic fields and eliminating imaging artifacts associated with high fields. By
      coupling with a remote-detection scheme, thereby improving the filling factor of
      the sample, we obtained time-resolved flow images of water with a temporal
      resolution of 0.1 s and spatial resolutions of 1.6 mm perpendicular to the flow
      and 4.5 mm along the flow. Potentially inexpensive, compact, and mobile, our
      technique provides a viable alternative for MRI detection with substantially
      enhanced sensitivity and time resolution for various situations where traditional
      MRI is not optimal.

PMID- 16885211
TI  - Entropy-driven spatial organization of highly confined polymers: lessons for the
      bacterial chromosome.
AB  - Despite recent progress in visualization experiments, the mechanism underlying
      chromosome segregation in bacteria still remains elusive. Here we address a basic
      physical issue associated with bacterial chromosome segregation, namely the
      spatial organization of highly confined, self-avoiding polymers (of nontrivial
      topology) in a rod-shaped cell-like geometry. Through computer simulations, we
      present evidence that, under strong confinement conditions, topologically
      distinct domains of a polymer complex effectively repel each other to maximize
      their conformational entropy, suggesting that duplicated circular chromosomes
      could partition spontaneously. This mechanism not only is able to account for the
      spatial separation per se but also captures the major features of the
      spatiotemporal organization of the duplicating chromosomes observed in
      Escherichia coli and Caulobacter crescentus.

PMID- 16885212
TI  - NF-kappaB-dependent induction of microRNA miR-146, an inhibitor targeted to
      signaling proteins of innate immune responses.
AB  - Activation of mammalian innate and acquired immune responses must be tightly
      regulated by elaborate mechanisms to control their onset and termination.
      MicroRNAs have been implicated as negative regulators controlling diverse
      biological processes at the level of posttranscriptional repression. Expression
      profiling of 200 microRNAs in human monocytes revealed that several of them (miR
      146a/b, miR-132, and miR-155) are endotoxin-responsive genes. Analysis of miR
      146a and miR-146b gene expression unveiled a pattern of induction in response to
      a variety of microbial components and proinflammatory cytokines. By means of
      promoter analysis, miR-146a was found to be a NF-kappaB-dependent gene.
      Importantly, miR-146a/b were predicted to base-pair with sequences in the 3' UTRs
      of the TNF receptor-associated factor 6 and IL-1 receptor-associated kinase 1
      genes, and we found that these UTRs inhibit expression of a linked reporter gene.
      These genes encode two key adapter molecules downstream of Toll-like and cytokine
      receptors. Thus, we propose a role for miR-146 in control of Toll-like receptor
      and cytokine signaling through a negative feedback regulation loop involving down
      regulation of IL-1 receptor-associated kinase 1 and TNF receptor-associated
      factor 6 protein levels.

PMID- 16885215
TI  - Antibodies as valuable neuroscience research tools versus reagents of mass
      distraction.

PMID- 16885213
TI  - Activation of heterotrimeric G proteins by Smoothened.
AB  - The mechanisms by which the activation of Smoothened (Smo), a protein essential
      to the actions of the Hedgehog family of secreted proteins, is translated into
      signals that converge on the Gli transcription factors are not fully understood.
      The seven-transmembrane structure of Smo has long implied the utilization of
      heterotrimeric GTP-binding regulatory proteins (G proteins); however, evidence in
      this regard has been indirect and contradictory. In the current study we
      evaluated the capacity of mammalian Smo to couple to G proteins directly. We
      found that Smo, by virtue of what appears to be constitutive activity, activates
      all members of the G(i) family but does not activate members of the G(s), G(q),
      and G(12) families. The activation is suppressed by cyclopamine and other
      inhibitors of Hedgehog signaling and is enhanced by the Smo agonist
      purmorphamine. Activation of G(i) by Smo is essential in the activation of Gli in
      fibroblasts, because disruption of coupling to G(i) with pertussis toxin inhibits
      the activation of Gli by Sonic hedgehog and a constitutively active form of Smo
      (SmoM2). However, G(i) does not provide a sufficient signal because a truncated
      form of Smo, although capable of activating G(i), does not effect activation of
      Gli. Rescue of pertussis toxin-inhibited activation of Gli by Sonic hedgehog can
      be achieved with a constitutively active Galpha(i)-subunit. The data suggest that
      Smo is in fact the source of two signals relevant to the activation of Gli: one
      involving G(i) and the other involving events at Smo's C-tail independent of
      G(i).

PMID- 16885216
TI  - Progression of cellular adaptations in medial prefrontal and orbitofrontal cortex
      in response to repeated amphetamine.
AB  - Recent theories on addiction implicate adaptive changes in prefrontal cortex
      (PFC) neurons in reinforcing and psychotomimetic properties of psychostimulants,
      yet little is known about how neuronal responses to these drugs change over time.
      Here we describe electrophysiological evidence for a progressive and sustained
      change in the response of PFC neurons to amphetamine during repeated exposure. In
      spontaneously behaving rats and in rats engaged in an instrumental responding
      task, we followed the activity of medial PFC (mPFC) and orbitofrontal cortex
      (OFC) neurons during daily exposure to amphetamine and after a post-withdrawal
      challenge. Repeated amphetamine increased the number of responsive neurons and
      the magnitude of responses and modified spontaneous burst patterns. These changes
      were apparent after a few exposures to amphetamine, were amplified after
      withdrawal, and were region specific in that repeated amphetamine increasingly
      produced inhibitory responses in mPFC and excitatory responses in OFC. In
      behaviorally engaged animals, the gradual enhancement in mPFC inhibition and OFC
      overactivation correlated with a progressive impairment of instrumental
      responding. Furthermore, these changes were evident predominately in neurons that
      displayed phasic responses during task-related events. These rapid-onset and
      sustained cellular adaptations suggest that even limited exposure to
      psychostimulants may reduce the influence of mPFC neurons on behavior while at
      the same time exaggerating information encoded by OFC neurons.

PMID- 16885218
TI  - Spatial memory formation and memory-enhancing effect of glucose involves
      activation of the tuberous sclerosis complex-Mammalian target of rapamycin
      pathway.
AB  - The tuberous sclerosis complex-mammalian target of rapamycin (TSC-mTOR) cascade
      integrates growth factor and nutritional signals to regulate the synthesis of
      specific proteins. Because both growth factor signaling and glucose have been
      implicated in memory formation, we questioned whether mTOR activity is required
      for long-term spatial memory formation and whether this cascade is involved in
      the memory-augmenting effect of centrally applied glucose. To test our
      hypothesis, we directly administered rapamycin (an inhibitor of mTOR), glucose, 5
      aminoimidazole-4-carboxamide-1beta-4-ribonucleoside (AICAR; an activator of AMP
      kinase), or glucose plus rapamycin into the dorsal hippocampus after we trained
      rats in the Morris water maze task. The results from these studies indicate that
      glucose enhances, whereas AICAR and rapamycin both impair, long-term spatial
      memory. Furthermore, the memory-impairing effect of targeted rapamycin
      administration could not be overcome by coadministration of glucose. Consistent
      with these behavioral results, biochemical analysis revealed that glucose and
      AICAR had opposing influences on the activation of the TSC-mTOR cascade, as
      indicated by the phosphorylation of ribosomal S6 kinase (S6K) and 4E binding
      protein 1 (4EBP1), targets of mTOR. Together, these findings suggest that memory
      formation requires the mTOR cascade and that the memory-enhancing effect of
      glucose involves its ability to activate this pathway.

PMID- 16885217
TI  - UNC-13 and UNC-10/rim localize synaptic vesicles to specific membrane domains.
AB  - Synaptic vesicles undergo a maturation step, termed priming, in which they become
      competent to fuse with the plasma membrane. To morphologically define the site of
      vesicle priming and identify fusion-competent synaptic vesicles, we combined a
      rapid physical-fixation technique with immunogold staining and high-resolution
      morphometric analysis at Caenorhabditis elegans neuromuscular junctions. In these
      presynaptic terminals, a subset of synaptic vesicles contact the plasma membrane
      within approximately 100 nm of a presynaptic dense projection. UNC-13, a protein
      required for vesicle priming, localizes to this same region of the plasma
      membrane. In an unc-13 null mutant, few synaptic vesicles contact the plasma
      membrane, suggesting that membrane-contacting synaptic vesicles represent the
      morphological correlates of primed vesicles. Interestingly, a subpopulation of
      membrane-contacting vesicles, located within 30 nm of a dense projection, are
      unperturbed in unc-13 mutants. We show that UNC-10/Rim, a protein implicated in
      presynaptic plasticity, localizes to dense projections and that loss of UNC
      10/Rim causes an UNC-13-independent reduction in membrane-contacting synaptic
      vesicles within 30 nm of the dense projections. Our data together identify a
      discrete domain for vesicle priming within 100 nm of dense projections and
      further suggest that UNC-10/Rim and UNC-13 separately contribute to the membrane
      localization of synaptic vesicles within this domain.

PMID- 16885219
TI  - Induction of autophagy in axonal dystrophy and degeneration.
AB  - Autophagy is a highly regulated cellular mechanism for the bulk degradation of
      cytoplasmic contents. It has been implicated in a variety of physiological and
      pathological conditions relevant to neurological diseases. However, the
      regulation of autophagy in neurons and its role in neuronal and axonal pathology
      are not yet understood. Using transgenic mice producing green fluorescent protein
      tagged autophagic marker microtubule-associated protein light chain 3 (GFP-LC3),
      we provide molecular evidence for the induction of autophagy in axonal dystrophy
      and degeneration in Purkinje cells of the Lurcher mice, a model for excitotoxic
      neurodegeneration. We show that the excitotoxic insult of Lurcher mutation
      triggers an early response of Purkinje cells involving accumulation of GFP-LC3
      labeled autophagosomes in axonal dystrophic swellings (a hallmark of CNS
      axonopathy). In brain, LC3 interacts with high affinity with the microtubule
      associated protein 1B (MAP1B). We show that MAP1B binds to LC3 of both cytosolic
      form (LC3I) and lipidated form (LC3II). Moreover, in cell culture, overexpression
      of MAP1B results in reduced LC3II levels and number of GFP-LC3-labeled
      autophagosomes; phosphorylated MAP1B is associated with GFP-LC3-labeled
      autophagosomes. Furthermore, in brain, phosphorylated MAP1B accumulates in axonal
      dystrophic swellings of degenerating Purkinje cells and binds to LC3 at increased
      level. Therefore, the MAP1B-LC3 interaction may participate in regulation of LC3
      associated autophagosomes in neurons, in particular at axons, under normal and
      pathogenic conditions. We propose that induction of autophagy serves as an early
      stress response in axonal dystrophy and may participate in the remodeling of axon
      structures.

PMID- 16885220
TI  - Restoring cerebral blood flow reveals neural regions critical for naming.
AB  - We identified areas of the brain that are critical for naming pictures of
      objects, using a new methodology for testing which components of a network of
      brain regions are essential for that task. We identified areas of hypoperfusion
      and structural damage with magnetic resonance perfusion- and diffusion-weighted
      imaging immediately after stroke in 87 individuals with impaired picture naming.
      These individuals were reimaged after 3-5 d, after a subset of patients underwent
      intervention to restore normal blood flow, to determine areas of the brain that
      had reperfused. We identified brain regions in which reperfusion was associated
      with improvement in picture naming. Restored blood flow to left posterior middle
      temporal/fusiform gyrus, Broca's area, and/or Wernicke's area accounted for most
      acute improvement after stroke. Results show that identifying areas of
      reperfusion that are associated with acute improvement of a function can reveal
      the brain regions essential for that function.

PMID- 16885221
TI  - Neural basis of embodiment: distinct contributions of temporoparietal junction
      and extrastriate body area.
AB  - Embodiment, the sense of being localized within one's physical body, is a
      fundamental aspect of the self. Recently, researchers have started to show that
      self and body processing require distinct brain mechanisms, suggesting two
      posterior brain regions as key loci: the temporoparietal junction (TPJ), which is
      involved in self processing and multisensory integration of body-related
      information; and the extrastriate body area (EBA), which responds selectively to
      human bodies and body parts. Here we used evoked potential mapping and a
      distributed linear inverse solution to show that activations in EBA and TPJ code
      differentially for embodiment and self location, because the location and timing
      of brain activation depended on whether mental imagery is performed with mentally
      embodied (EBA) or disembodied (TPJ) self location. In a second experiment, we
      showed that only EBA activation, related to embodied self location, but not TPJ
      activation, related to disembodied self location, was modified by the subjects'
      body position during task performance (supine or sitting). This suggests that
      embodied self location and actual body location share neural mechanisms.
      Collectively, these data show that distributed brain activity at the EBA and TPJ
      as well as their timing are crucial for the coding of the self as embodied and as
      spatially situated within the human body.

PMID- 16885222
TI  - Slit proteins regulate distinct aspects of retinal ganglion cell axon guidance
      within dorsal and ventral retina.
AB  - An early step in the formation of the optic pathway is the directed extension of
      retinal ganglion cell (RGC) axons into the optic fiber layer (OFL) of the retina
      in which they project toward the optic disc. Using analysis of knock-out mice and
      in vitro assays, we found that, in the mammalian retina, Slit1 and Slit2, known
      chemorepellents for RGC axons, regulate distinct aspects of intraretinal
      pathfinding in different regions of the retina. In ventral and, to a much lesser
      extent, dorsal retina, Slits help restrict RGC axons to the OFL. Additionally,
      within dorsal retina exclusively, Slit2 also regulates the initial polarity of
      outgrowth from recently differentiated RGCs located in the retinal periphery.
      This regional specificity occurs despite the fact that Slits are expressed
      throughout the retina, and both dorsal and ventral RGCs are responsive to Slits.
      The gross morphology and layering of the retina of the slit-deficient retinas is
      normal, demonstrating that these distinct guidance defects are not the result of
      changes in the organization of the tissue. Although displaced or disorganized,
      the aberrant axons within both dorsal and ventral retina exit the eye. We also
      have found that the lens, which because of its peripheral location within the
      developing eye is ideally located to influence the initial direction of RGC axon
      outgrowth, secretes Slit2, suggesting this is the source of Slit regulating OFL
      development. These data demonstrate clearly that multiple mechanisms exist in the
      retina for axon guidance of which Slits are an important component.

PMID- 16885223
TI  - Adenosine and sleep homeostasis in the Basal forebrain.
AB  - It is currently hypothesized that the drive to sleep is determined by the
      activity of the basal forebrain (BF) cholinergic neurons, which release adenosine
      (AD), perhaps because of increased metabolic activity associated with the
      neuronal discharge during waking, and the accumulating AD begins to inhibit these
      neurons so that sleep-active neurons can become active. This hypothesis grew from
      the observation that AD induces sleep and AD levels increase with wake in the
      basal forebrain, but surprisingly it still remains untested. Here we directly
      test whether the basal forebrain cholinergic neurons are central to the AD
      regulation of sleep drive by administering 192-IgG-saporin to lesion the BF
      cholinergic neurons and then measuring AD levels in the BF. In rats with 95%
      lesion of the BF cholinergic neurons, AD levels in the BF did not increase with 6
      h of prolonged waking. However, the lesioned rats had intact sleep drive after 6
      and 12 h of prolonged waking, indicating that the AD accumulation in the BF is
      not necessary for sleep drive. Next we determined that, in the absence of the BF
      cholinergic neurons, the selective adenosine A1 receptor agonist N6
      cyclohexyladenosine, administered to the BF, continued to be effective in
      inducing sleep, indicating that the BF cholinergic neurons are not essential to
      sleep induction. Thus, neither the activity of the BF cholinergic neurons nor the
      accumulation of AD in the BF during wake is necessary for sleep drive.

PMID- 16885224
TI  - Dopamine replacement therapy does not restore the full spectrum of normal
      pallidal activity in the 1-methyl-4-phenyl-1,2,3,6-tetra-hydropyridine primate
      model of Parkinsonism.
AB  - Current physiological studies emphasize the role of neuronal oscillations and
      synchronization in the pathophysiology of Parkinson's disease; however, little is
      known about their specific roles in the neuronal substrate of dopamine
      replacement therapy (DRT). We investigated oscillatory activity and correlations
      throughout the different states of levodopa-naive parkinsonism as well as "Off
      On" and dyskinetic states of DRT in the external globus pallidum (GPe) of
      tremulous (vervet) and rigid-akinetic (macaque) monkeys and in the internal
      globus pallidum (GPi) of the vervet monkey. We found that, although oscillatory
      activity of cells and interneuronal correlation in both pallidal segments
      increases after induction of parkinsonism with 1-methyl-4-phenyl-1,2,3,6-tetra
      hydropyridine (MPTP) and decreases in response to DRT, important differences
      exist between the two pallidal segments. In the GPi, the fraction of oscillatory
      cells and relative power of oscillations were significantly higher than in the
      GPe, and the dominant frequency was within the range of 7.5-13.5 Hz compared with
      a range of 4.5-7.5 Hz within the GPe. The interneuronal correlations were mostly
      oscillatory in the GPi, whereas at least half are non-oscillatory in the GPe. We
      demonstrate that the tremor characteristics after exposure to DRT do not resemble
      those of the normal or the levodopa-naive state. Moreover, although DRT reverses
      the MPTP-induced neuronal changes (rate, pattern, and pairwise correlations), the
      balance between GPe and GPi fails to restore. We therefore suggest that this
      imbalance reflects additional abnormal organization of the basal ganglia networks
      in response to dopamine replacement and may constitute the physiological
      substrate of the limitations and side effects of chronic DRT.

PMID- 16885225
TI  - The role of protein interaction motifs in regulating the polarity and clustering
      of the metabotropic glutamate receptor mGluR1a.
AB  - When expressed in cultured hippocampal neurons, the metabotropic glutamate
      receptor mGluR1a is polarized to dendrites and concentrated at postsynaptic
      sites. We used a mutational analysis to determine how previously identified
      protein interaction motifs in the C terminus of mGluR1a contribute to its
      localization. Our results show that the polyproline motif that mediates
      interaction with Homer family proteins is critical for the synaptic clustering of
      mGluR1a. A single point mutation in this motif, which prevents the binding of
      Homer with mGluR1a, reduced its colocalization with a postsynaptic marker to near
      chance levels but did not affect its dendritic polarity. In contrast, deleting
      the PDZ (postsynaptic density-95/Discs large/zona occludens-1) binding domain,
      which interacts with Tamalin and Shank, had no effect on synaptic localization.
      Neither of these protein interaction motifs is important for trafficking to the
      plasma membrane or for polarization to dendrites. Although deleting the entire C
      terminus of mGluR1a only modestly reduced its dendritic polarity, this domain was
      sufficient to redirect an unpolarized reporter protein to dendrites. These
      observations suggest that mGluR1a contains redundant dendritic targeting signals.
      Together, our results indicate that the localization of mGluR1a involves two
      distinct steps, one that targets the protein to dendrites and a second that
      sequesters it at postsynaptic sites; different protein interactions motifs
      mediate each step.

PMID- 16885226
TI  - Prolactin modulates TRPV1 in female rat trigeminal sensory neurons.
AB  - Sex dependency in pain perception is well documented and is thought to be
      attributable to the effect of reproductive hormones on nociceptive processing. In
      the present study, we evaluated whether estradiol alters gene transcription in
      the trigeminal ganglia (TG) of ovariectomized rats (OVX). These experiments
      demonstrated a dramatic (40-fold) upregulation of prolactin (PRL) expression in
      TG by 17-beta-estradiol (E2). PRL expression was restricted to TG neurons and was
      highly overlapped with transient potential receptor vanilloid type 1 (TRPV1)
      (approximately 90%) in TG. Additionally, PRL is released from neurons during
      stimulation. Both forms of PRL receptors (PRLRs), short and long, were also
      present in TG neurons. Moreover, expression of the long PRLRs was under control
      of estradiol. We next evaluated the novel hypothesis that PRL acts as a
      neuromodulator of sensory neurons. PRL pretreatment significantly enhanced
      capsaicin-evoked inward currents, calcium influx, and immunoreactive calcitonin
      gene-related peptide release from cultured TG neurons. This PRL modulation of
      capsaicin responses was abolished by withdrawal of E2 from TG cultures.
      Biochemical analysis demonstrated that PRL increased (>50%) phosphorylation
      levels of TRPV1 in TG. In a behavioral test, PRL pretreatment significantly
      potentiated capsaicin-evoked nocifensive behavior in female rats at proestrous
      and in OVX rats after E2 treatment. The in vivo potentiating effect of PRL on
      capsaicin responses was also dependent on E2. Collectively, these data
      demonstrate that PRL is a novel modulator of sensory neurons tightly regulated by
      E2. These findings are consistent with the hypothesis that PRL could contribute
      to the development of certain pain disorders, possibly including those modulated
      by estrogen.

PMID- 16885227
TI  - Actin-dependent activation of presynaptic silent synapses contributes to long
      term synaptic plasticity in developing hippocampal neurons.
AB  - Developing neurons have greater capacity in experience-dependent plasticity than
      adult neurons but the molecular mechanism is not well understood. Here we report
      a developmentally regulated long-term synaptic plasticity through actin-dependent
      activation of presynaptic silent synapses in cultured hippocampal neurons. Live
      FM 1-43 imaging and retrospective immunocytochemistry revealed that many
      presynaptic boutons in immature neurons are functionally silent at resting
      conditions, but can be converted into active ones after repetitive neuronal
      stimulation. The activation of presynaptic silent synapses is dependent on L-type
      calcium channels and protein kinase A (PKA)/PKC signaling pathways. Moreover,
      blocking actin polymerization with latrunculin A and cytochalasin B abolishes
      long-term increase of presynaptic functional boutons induced by repetitive
      stimulation, whereas actin polymerizer jasplakinolide increases the number of
      active boutons in immature neurons. In mature neurons, however, presynaptic
      boutons are mostly functional and repetitive stimulation did not induce
      additional enhancement. Quantitative immunostaining with phalloidin revealed a
      significant increase in axonal F-actin level after repetitive stimulation in
      immature but not mature neurons. These results suggest that actin-dependent
      activation of presynaptic silent synapses contributes significantly to the long
      term synaptic plasticity during neuronal development.

PMID- 16885228
TI  - Inverted-U profile of dopamine-NMDA-mediated spontaneous avalanche recurrence in
      superficial layers of rat prefrontal cortex.
AB  - Prefrontal cortex (PFC) functions, such as working memory, attention selection,
      and memory retrieval, depend critically on dopamine and NMDA receptor activation
      by way of an inverted-U-shaped pharmacological profile. Although single neuron
      responses in the PFC have shown some aspects of this profile, a network dynamic
      that follows the dopamine-NMDA dependence has not been identified. We studied
      neuronal network activity in acute medial PFC slices of adult rats by recording
      local field potentials (LFPs) with microelectrode arrays. Bath application of
      dopamine or the dopamine D1 agonist SKF38393 [(+/-)-1-phenyl-2,3,4,5-tetrahydro
      (1H)-3-benzazepine-7,8-diol hydrochloride] in combination with NMDA induced
      spontaneous LFPs predominantly in superficial cortex layers. The LFPs at single
      electrodes were characterized by sharp negative peaks that were clustered in time
      across electrodes revealing diverse spatiotemporal patterns on the array. The
      pattern formation required fast GABAergic transmission, coactivation of the
      dopamine D1 and NMDA receptor, and depended in an inverted-U profile on dopamine.
      At moderate concentrations of dopamine or the dopamine D1 agonist, the pattern
      size distribution formed a power law with exponent alpha = -1.5, indicating that
      patterns are organized in the form of neuronal avalanches, thereby maximizing
      spatial correlations in the network. At lower or higher concentrations, alpha was
      more negative than -1.5, indicating reduced spatial correlations. Likewise, at
      moderate dopamine concentrations, the avalanche rate and recurrence of specific
      avalanches was maximal with recurrence frequencies after a "power law"-like heavy
      tail distribution with a slope of -2.4. We suggest that the dopamine-NMDA
      dependent spontaneous recurrence of specific avalanches in superficial cortical
      layers might facilitate integrative and associative aspects of PFC functions.

PMID- 16885229
TI  - Prefibrillar amyloid aggregates could be generic toxins in higher organisms.
AB  - More than 40 human diseases are associated with fibrillar deposits of specific
      peptides or proteins in tissue. Amyloid fibrils, or their precursors, can be
      highly toxic to cells, suggesting their key role in disease pathogenesis.
      Proteins not associated with any disease are able to form oligomers and amyloid
      assemblies in vitro displaying structures and cytotoxicity comparable with those
      of aggregates of disease-related polypeptides. In isolated cells, such toxicity
      has been shown to result from increased membrane permeability with disruption of
      ion homeostasis and oxidative stress. Here we microinjected into the nucleus
      basalis magnocellularis of rat brains aggregates of an Src homology 3 domain and
      the N-terminal domain of the prokaryotic HypF, neither of which is associated
      with amyloid disease. Prefibrillar aggregates of both proteins, but not their
      mature fibrils or soluble monomers, impaired cholinergic neuron viability in a
      dose-dependent manner similar to that seen in cell cultures. Contrary to the
      situation with cultured cells, however, under our experimental conditions, cell
      stress in tissue is not followed by a comparable level of cell death, a result
      that is very likely to reflect the presence of protective mechanisms reducing
      aggregate toxicity. These findings support the hypothesis that neurodegenerative
      disorders result primarily from a generic cell dysfunction caused by early
      misfolded species in the aggregation process.

PMID- 16885230
TI  - Dysfunctional long-range coordination of neural activity during Gestalt
      perception in schizophrenia.
AB  - Recent theoretical and empirical research on schizophrenia converges on the
      notion that core aspects of the pathophysiology of the disorder may arise from a
      dysfunction in the coordination of distributed neural activity. Synchronization
      of neural responses in the beta-band (15-30 Hz) and gamma-band range (30-80 Hz)
      has been implicated as a possible neural substrate for dysfunctional coordination
      in schizophrenia. To test this hypothesis, we examined the electroencephalography
      (EEG) activity in 19 patients with a Diagnostic and Statistical Manual of Mental
      Disorder, edition IV criteria, diagnosis of schizophrenia and 19 healthy control
      subjects during a Gestalt perception task. EEG data were analyzed for phase
      synchrony and induced spectral power as an index of neural synchronization.
      Schizophrenia patients were impaired significantly in the detection of images
      that required the grouping of stimulus elements into coherent object
      representations. This deficit was accompanied by longer reaction times in
      schizophrenia patients. Deficits in Gestalt perception in schizophrenia patients
      were associated with reduced phase synchrony in the beta-band (20-30 Hz), whereas
      induced spectral power in the gamma-band (40-70 Hz) was mainly intact. Our
      findings suggest that schizophrenia patients are impaired in the long-range
      synchronization of neural responses, which may reflect a core deficit in the
      coordination of neural activity and underlie the specific cognitive dysfunctions
      associated with the disorder.

PMID- 16885231
TI  - The anterior intraparietal sulcus mediates grasp execution, independent of
      requirement to update: new insights from transcranial magnetic stimulation.
AB  - Although a role of the intraparietal sulcus (IPS) in grasping is becoming
      evident, the specific contribution of regions within the IPS remains undefined.
      In this vein, transcranial magnetic stimulation (TMS) was delivered to the
      anterior (aIPS), middle (mIPS), and caudal (cIPS) IPS in two tasks designed to
      dissociate the potential roles of the IPS in either grasp planning or execution
      (task 1) and its involvement in error detection or error correction (task 2).
      Determining the involvement of specific regions of the IPS in perceptual
      (planning and error detection) versus motor (execution and correction) components
      of grasping allowed us to assess the ecological validity of competing
      computational models attempting to simulate reach-to-grasp movements. In task 1,
      we demonstrate that, when no on-line adjustment is necessary, TMS to aIPS (but
      not mIPS or cIPS) disrupts grasping; this disruption is only elicited when TMS is
      applied during the execution (but not the planning) phase of the movement. Task 2
      reveals that TMS to aIPS (but not mIPS or cIPS) disrupts grasping in the presence
      of a perturbation; this disruption is only elicited when TMS is applied during
      the error correction (but not error detection) phase of the movement. We propose
      that the specific contribution of the aIPS in grasping is in the on-line
      computation of a difference vector based on motor goal, efference copy, and
      sensory inputs. This computation is performed for both stable and perturbed motor
      goals.

PMID- 16885232
TI  - Nonlinear [Ca2+] signaling in dendrites and spines caused by activity-dependent
      depression of Ca2+ extrusion.
AB  - Spine Ca2+ triggers the induction of synaptic plasticity and other adaptive
      neuronal responses. The amplitude and time course of Ca2+ signals specify the
      activation of the signaling pathways that trigger different forms of plasticity
      such as long-term potentiation and depression. The shapes of Ca2+ signals are
      determined by the dynamics of Ca2+ sources, Ca2+ buffers, and Ca2+ extrusion
      mechanisms. Here we show in rat CA1 pyramidal neurons that plasma membrane Ca2+
      pumps (PMCAs) and Na+/Ca2+ exchangers are the major Ca2+ extrusion pathways in
      spines and small dendrites. Surprisingly, we found that Ca2+ extrusion via PMCA
      and Na+/Ca2+ exchangers slows in an activity-dependent manner, mediated by
      intracellular Na+ and Ca2+ accumulations. This activity-dependent depression of
      Ca2+ extrusion is, in part, attributable to Ca2+-dependent inactivation of PMCAs.
      Ca2+ extrusion recovers from depression with a time constant of 0.5 s. Depression
      of Ca2+ extrusion provides a positive feedback loop, converting small differences
      in stimuli into large differences in Ca2+ concentration. Depression of Ca2+
      extrusion produces Ca2+ concentration dynamics that depend on the history of
      neuronal activity and therefore likely modulates the induction of synaptic
      plasticity.

PMID- 16885233
TI  - RNA interference screen reveals an essential role of Nedd4-2 in dopamine
      transporter ubiquitination and endocytosis.
AB  - The function of the dopamine transporter (DAT) to terminate dopamine
      neurotransmission is regulated by endocytic trafficking of DAT. To elucidate the
      mechanisms of DAT endocytosis, we generated a fully functional mutant of the
      human DAT in which a hemagglutinin epitope (HA) was incorporated into the second
      extracellular loop. The endocytosis assay, based on the uptake of an HA antibody,
      was designed to study constitutive- and protein kinase C (PKC)-dependent
      internalization of HA-DAT expressed in non-neuronal cells and rat dopaminergic
      neurons. Large-scale RNA interference analysis of PKC-dependent endocytosis of HA
      DAT revealed the essential and specific role of an E3 ubiquitin ligase, Nedd4-2
      (neural precursor cell expressed, developmentally downregulated 4-2), as well as
      the involvement of adaptor proteins present in clathrin-coated pits, such as
      epsin, Eps15 (epidermal growth factor pathway substrate clone 15), and Eps15R
      (Eps15-related protein). Depletion of Nedd4-2 resulted in a dramatic reduction of
      PKC-dependent ubiquitination of DAT. Endogenous Nedd4-2, epsin, and Eps15 were
      coimmunoprecipitated with heterologously expressed human HA-DAT and endogenous
      DAT isolated from rat striatum. A new mechanistic model of DAT endocytosis is
      proposed whereby the PKC-induced ubiquitination of DAT mediated by Nedd4-2 leads
      to interaction of DAT with adaptor proteins in coated pits and acceleration of
      DAT endocytosis.

PMID- 16885234
TI  - Immune cells contribute to myelin degeneration and axonopathic changes in mice
      overexpressing proteolipid protein in oligodendrocytes.
AB  - Overexpression of the major myelin protein of the CNS, proteolipid protein (PLP),
      leads to late-onset degeneration of myelin and pathological changes in axons.
      Based on the observation that in white matter tracts of these mutants both CD8+ T
      lymphocytes and CD11b+ macrophage-like cells are numerically elevated, we tested
      the hypothesis that these cells are pathologically involved in the primarily
      genetically caused neuropathy. Using flow cytometry of mutant brains, CD8+ cells
      could be identified as activated effector cells, and confocal microscopy revealed
      a close association of the T-cells with MHC-I+ (major histocompatibility complex
      class I positive) oligodendrocytes. Crossbreeding the myelin mutants with mice
      deficient in the recombination activating gene-1 (RAG-1) lacking mature T- and B
      lymphocytes led to a reduction of the number of CD11b+ cells and to a substantial
      alleviation of pathological changes. In accordance with these findings, magnetic
      resonance imaging revealed less ventricular enlargement in the double mutants,
      partially because of more preserved corpora callosa. To investigate the role of
      CD8+ versus CD4+ T-lymphocytes, we reconstituted the myelin-RAG-1 double mutants
      with bone marrow from either CD8-negative (CD4+) or CD4-negative (CD8+) mice. The
      severe ventricular enlargement was only found when the double mutants were
      reconstituted with bone marrow from CD8+ mice, suggesting that the CD8+
      lymphocytes play a critical role in the immune-related component of myelin
      degeneration in the mutants. These findings provide strong evidence that a
      primary glial damage can cause secondary immune reactions of pathological
      significance as it has been suggested for some forms of multiple sclerosis and
      other leukodystrophies.

PMID- 16885235
TI  - A matrix of 3,4-diaminobenzophenone for the analysis of oligonucleotides by
      matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.
AB  - A new matrix of 3,4-diaminobenzophenone (DABP) was demonstrated to be
      advantageous in the analysis of oligonucleotides by matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry. With DABP as a matrix,
      intact oligonucleotide ions can be readily produced with lower laser powers,
      resulting in better detection limits, less fragmentation and fewer alkali metal
      ion adducts compared with the results obtained with conventional matrices.
      Importantly, minimal fragmentation and fewer alkali metal ion adducts were seen
      even at low concentrations of oligonucleotides. It was also found that samples
      prepared with DABP are highly homogenous and therefore reducing the need for
      finding 'sweet' spots in MALDI. In addition, excellent shot-to-shot
      reproducibility, resolution and signal-to-noise ratio were seen with DABP as the
      matrix.

PMID- 16885236
TI  - Production of transmitochondrial cybrids containing naturally occurring
      pathogenic mtDNA variants.
AB  - The human mitochondrial genome (mtDNA) encodes polypeptides that are critical for
      coupling oxidative phosphorylation. Our detailed understanding of the molecular
      processes that mediate mitochondrial gene expression and the structure-function
      relationships of the OXPHOS components could be greatly improved if we were able
      to transfect mitochondria and manipulate mtDNA in vivo. Increasing our knowledge
      of this process is not merely of fundamental importance, as mutations of the
      mitochondrial genome are known to cause a spectrum of clinical disorders and have
      been implicated in more common neurodegenerative disease and the ageing process.
      In organellar or in vitro reconstitution studies have identified many factors
      central to the mechanisms of mitochondrial gene expression, but being able to
      investigate the molecular aetiology of a limited number of cell lines from
      patients harbouring mutated mtDNA has been enormously beneficial. In the absence
      of a mechanism for manipulating mtDNA, a much larger pool of pathogenic mtDNA
      mutations would increase our knowledge of mitochondrial gene expression. Colonic
      crypts from ageing individuals harbour mutated mtDNA. Here we show that by
      generating cytoplasts from colonocytes, standard fusion techniques can be used to
      transfer mtDNA into rapidly dividing immortalized cells and, thereby, respiratory
      deficient transmitochondrial cybrids can be isolated. A simple screen identified
      clones that carried putative pathogenic mutations in MTRNR1, MTRNR2, MTCOI and
      MTND2, MTND4 and MTND6. This method can therefore be exploited to produce a
      library of cell lines carrying pathogenic human mtDNA for further study.

PMID- 16885237
TI  - NMR structure of the three quasi RNA recognition motifs (qRRMs) of human hnRNP F
      and interaction studies with Bcl-x G-tract RNA: a novel mode of RNA recognition.
AB  - The heterogeneous nuclear ribonucleoprotein (hnRNP) F belongs to the hnRNP H
      family involved in the regulation of alternative splicing and polyadenylation and
      specifically recognizes poly(G) sequences (G-tracts). In particular, hnRNP F
      binds a G-tract of the Bcl-x RNA and regulates its alternative splicing, leading
      to two isoforms, Bcl-x(S) and Bcl-x(L), with antagonist functions. In order to
      gain insight into G-tract recognition by hnRNP H members, we initiated an NMR
      study of human hnRNP F. We present the solution structure of the three quasi RNA
      recognition motifs (qRRMs) of hnRNP F and identify the residues that are
      important for the interaction with the Bcl-x RNA by NMR chemical shift
      perturbation and mutagenesis experiments. The three qRRMs exhibit the canonical
      betaalphabetabetaalphabeta RRM fold but additional secondary structure elements
      are present in the two N-terminal qRRMs of hnRNP F. We show that qRRM1 and qRRM2
      but not qRRM3 are responsible for G-tract recognition and that the residues of
      qRRM1 and qRRM2 involved in G-tract interaction are not on the beta-sheet surface
      as observed for the classical RRM but are part of a short beta-hairpin and two
      adjacent loops. These regions define a novel interaction surface for RNA
      recognition by RRMs.

PMID- 16885238
TI  - Protein structure database search and evolutionary classification.
AB  - As more protein structures become available and structural genomics efforts
      provide structural models in a genome-wide strategy, there is a growing need for
      fast and accurate methods for discovering homologous proteins and evolutionary
      classifications of newly determined structures. We have developed 3D-BLAST, in
      part, to address these issues. 3D-BLAST is as fast as BLAST and calculates the
      statistical significance (E-value) of an alignment to indicate the reliability of
      the prediction. Using this method, we first identified 23 states of the
      structural alphabet that represent pattern profiles of the backbone fragments and
      then used them to represent protein structure databases as structural alphabet
      sequence databases (SADB). Our method enhanced BLAST as a search method, using a
      new structural alphabet substitution matrix (SASM) to find the longest common
      substructures with high-scoring structured segment pairs from an SADB database.
      Using personal computers with Intel Pentium4 (2.8 GHz) processors, our method
      searched more than 10 000 protein structures in 1.3 s and achieved a good
      agreement with search results from detailed structure alignment methods. [3D
      BLAST is available at http://3d-blast.life.nctu.edu.tw].

PMID- 16885240
TI  - Carbon nanotubes selective destabilization of duplex and triplex DNA and inducing
      B-A transition in solution.
AB  - Single-walled carbon nanotubes (SWNTs) have been considered as the leading
      candidate for nanodevice applications ranging from gene therapy and novel drug
      delivery to membrane separations. The miniaturization of DNA-nanotube devices for
      biological applications requires fully understanding DNA-nanotube interaction
      mechanism. We report here, for the first time, that DNA destabilization and
      conformational transition induced by SWNTs are sequence-dependent. Contrasting
      changes for SWNTs binding to poly[dGdC]:poly[dGdC] and poly[dAdT]:poly[dAdT] were
      observed. For GC homopolymer, DNA melting temperature was decreased 40 degrees C
      by SWNTs but no change for AT-DNA. SWNTs can induce B-A transition for GC-DNA but
      AT-DNA resisted the transition. Our circular dichroism, competitive binding assay
      and triplex destabilization studies provide direct evidence that SWNTs induce DNA
      B-A transition in solution and they bind to the DNA major groove with GC
      preference.

PMID- 16885239
TI  - Formation of isodialuric acid lesion within DNA oligomers via one-electron
      oxidation of 5-hydroxyuracil: characterization, stability and excision repair.
AB  - 5-Hydroxyuracil is a major oxidized nucleobase that can be generated by the
      action of (*)OH radical and one-electron oxidants. The latter modified base that
      exhibits a low ionization potential is highly susceptible to further degradation
      upon exposure to various oxidants. Emphasis was placed in this work on the
      formation and characterization of one-electron oxidation products of 5
      hydroxyuracil within DNA fragments of defined sequence. For this purpose, 5
      hydroxyuracil containing single- and double-stranded oligonucleotides of various
      lengths were synthesized and then exposed to the oxidizing action of iridium
      salts. Isodialuric acid was found to be formed almost quantitatively by a one
      electron oxidation mechanism for which relevant information was inferred from a
      freeze-quenched ESR study. Information on the stability of isodialuric acid thus
      formed and its conversion products in aqueous solutions was also gained from
      experiments performed at acidic, neutral and alkali pH's. Moreover, biochemical
      features dealing with the substrate specificity of several bacterial and yeast
      base excision repair enzymes to remove isodialuric acid from site-specifically
      modified DNA fragments were determined.

PMID- 16885243
TI  - Near misses and research subjects.

PMID- 16885241
TI  - Genome-wide screening for cis-regulatory variation using a classical diallel
      crossing scheme.
AB  - Large-scale screening studies carried out to date for genetic variants that
      affect gene regulation are generally limited to descriptions of differences in
      allele-specific expression (ASE) detected in vivo. Allele-specific differences in
      gene expression provide evidence for a model whereby cis-acting genetic variation
      results in differential expression between alleles. Such gene surveys for
      regulatory variation are a first step in identifying the specific nucleotide
      changes that govern gene expression differences, but they leave the underlying
      mechanisms unexplored. Here, we propose a quantitative genetics approach to
      perform a genome-wide analysis of ASE differences (GASED). The GASED approach is
      based on a diallel design that is often used in plant breeding programs to
      estimate general combining abilities (GCA) of specific inbred lines and to
      identify high-yielding hybrid combinations of parents based on their specific
      combining abilities (SCAs). In a context of gene expression, the values of GCA
      and SCA parameters allow cis- and trans-regulatory changes to be distinguished
      and imbalances in gene expression to be ascribed to cis-regulatory variation.
      With this approach, a total of 715 genes could be identified that are likely to
      carry allelic polymorphisms responsible for at least a 1.5-fold allelic
      expression difference in a total of 10 diploid Arabidopsis thaliana hybrids. The
      major strength of the GASED approach, compared to other ASE detection methods, is
      that it is not restricted to genes with allelic transcript variants. Although a
      false-positive rate of 9/41 was observed, the GASED approach is a valuable pre
      screening method that can accelerate systematic surveys of naturally occurring
      cis-regulatory variation among inbred lines for laboratory species, such as
      Arabidopsis, mouse, rat and fruitfly, and economically important crop species,
      such as corn.

PMID- 16885244
TI  - Hierarchies: the Berlin Wall of patient safety.

PMID- 16885245
TI  - Defining the technical skills of teamwork in surgery.
AB  - Developments in surgical technology and procedure have accelerated and altered
      the work carried out in the operating theatre/room, but team modelling and
      training have not co-evolved. Evidence suggests that team structure and role
      allocation are sometimes unclear and contentious, and coordination and
      communication are not fully effective. To improve teamwork, clinicians need
      models that specify team resources, structure, process and tasks. They also need
      measures to assess performance and methods to train teamwork strategically. An
      effective training strategy might be to incorporate teamwork with other technical
      skills training in simulation. However, the measures employed for enhancing
      teamwork in training and practice will need to vary in their object of analysis,
      level of technical specificity, and system scope.

PMID- 16885246
TI  - Decline in ICU adverse events, nosocomial infections and cost through a quality
      improvement initiative focusing on teamwork and culture change.
AB  - BACKGROUND: Nosocomial infections occur in approximately 10% of patients in
      intensive care units (ICUs). Several studies have shown that a quality
      improvement initiative can reduce nosocomial infections, mortality, and cost.
      CONTEXT: Our hospital is located in Northern Mississippi and has a 28 bed Medical
      Surgical ICU unit with 95% occupancy. We joined the ICU collaborative with the
      IMPACT initiative of the Institute of Healthcare Improvement (IHI) in October
      2002. A preliminary prospective before (fiscal year (FY) 2001-2) and after (FY
      2003) hypothesis generating study was conducted of outcomes resulting from small
      tests of change in the management of ICU patients. KEY MEASURES FOR IMPROVEMENT:
      Nosocomial infection rates, adverse events per ICU day, average length of stay,
      and average cost per ICU episode. STRATEGY FOR CHANGE: Four changes were
      implemented: (1) physician led multidisciplinary rounds; (2) daily "flow" meeting
      to assess bed availability; (3) "bundles" (sets of evidence based best
      practices); and (4) culture changes with a focus on the team decision making
      process. EFFECTS OF CHANGE: Between baseline and re-measurement periods,
      nosocomial infection rates declined for ventilator associated pneumonia (from 7.5
      to 3.2 per 1000 ventilator days, p = 0.04) and bloodstream infections (from 5.9
      to 3.1 per 1000 line days, p = 0.03), with a downward trend in the rate of
      urinary tract infections (from 3.8 to 2.4 per 1000 catheter days, p = 0.17).
      There was a strong downward trend in the rates of adverse events in the ICU as
      well as the average length of stay per episode. From FY 2002 to FY 2003 the cost
      per ICU episode fell from $3406 to $2973. LESSONS LEARNED: A systematic approach
      through collaboration with IHI's IMPACT initiative may have contributed to
      significant improvements in care in the ICU setting. Multidisciplinary teams
      appeared to improve communication, and bundles provided consistency of evidence
      based practices. The flow meetings allowed for rapid prioritization of activity
      and a new decision making culture empowered team members. The impact of these
      changes needs to be assessed more widely using rigorous study designs.

PMID- 16885247
TI  - Oral anticoagulation in a pediatric hospital: impact of a quality improvement
      initiative on warfarin management strategies.
AB  - BACKGROUND: There are potential risks associated with the use of warfarin in
      children, particularly as the dosing requirements may decrease as patients get
      older. CONTEXT: Our facility is a 715-bed freestanding pediatric tertiary care
      center with a large cardiac surgery center. A significant number of patients
      receive warfarin for treatment or prophylaxis of thromboembolic events while in
      hospital. KEY MEASURES FOR IMPROVEMENT: Initial dose of warfarin and time taken
      to achieve goal therapeutic international normalized ratio (INR). STRATEGIES FOR
      CHANGE: The intervention included: (1) revision of hospital drug formulary so
      that warfarin dosing was in accordance with the most recent guidelines; (2)
      warfarin administration restricted to one time of the day (12.00 noon); (3)
      target therapeutic INR level documented with each warfarin order; and (4)
      pharmacy computer system mandated that the pharmacist confirmed the target INR,
      documented the most current INR, and compared the dose with the formulary
      guidelines. If the warfarin dose was not in accordance with the formulary
      guidelines, the pharmacist contacted the physician and made dosing
      recommendations according to the guidelines. EFFECTS OF CHANGE: The number of
      patients with supratherapeutic INR values during the hospital admission was
      decreased by more than 50% and goal INR values were documented more frequently in
      the medical record. There was also an increase in subtherapeutic INR values. The
      intervention had no effect on the time taken to achieve the goal therapeutic INR.
      LESSONS LEARNED: Instituting changes in a number of aspects of anticoagulation
      management and incorporating an intensive educational effort across a breadth of
      healthcare providers can improve anticoagulation management with warfarin in
      challenging patient populations such as children. Similar methods could possibly
      improve anticoagulation with other agents such as unfractionated heparin or low
      molecular weight heparin.

PMID- 16885248
TI  - Using human error theory to explore the supply of non-prescription medicines from
      community pharmacies.
AB  - BACKGROUND: The importance of theory in underpinning interventions to promote
      effective professional practice is gaining recognition. The Medical Research
      Council framework for complex interventions has assisted in promoting awareness
      and adoption of theory into study design. Human error theory has previously been
      used by high risk industries but its relevance to healthcare settings and patient
      safety requires further investigation. This study used this theory as a framework
      to explore non-prescription medicine supply from community pharmacies. The
      relevance to other healthcare settings and behaviours is discussed. METHOD: A 25%
      random sample was made of 364 observed consultations for non-prescription
      medicines. Each of the 91 consultations was assessed by two groups: a consensus
      group (stage 1) to identify common problems with the consultation process, and an
      expert group (stages 2 and 3) to apply human error theory to these consultations.
      Paired assessors (most of whom were pharmacists) categorised the perceived
      problems occurring in each consultation (stage 1). During stage 2 paired
      assessors from an expert group (comprising patient safety experts, community
      pharmacists and psychologists) considered whether each consultation was compliant
      with professional guidelines for the supply of pharmacy medicines. Each non
      compliant consultation identified during stage 2 was then categorised as a
      slip/lapse, mistake, or violation using human error theory (stage 3). RESULTS:
      During stage 1 most consultations (n = 75, 83%) were deemed deficient in
      information exchange. At stage 2, paired assessors varied in attributing non
      compliance to specific error types. Where agreement was achieved, the error type
      most often selected was "violation" (n = 27, 51.9%, stage 3). Consultations
      involving product requests were less likely to be guideline compliant than
      symptom presentations (OR 0.30, 95% CI 0.10 to 0.95, p = 0.05). CONCLUSIONS: The
      large proportion of consultations classified as violations suggests that either
      pharmacy staff are unaware of professional guidelines and thus do not follow them
      (therefore these acts would not be violations), or that they knowingly violate
      the guidelines due to reasons that need further research. The methods presented
      here could be used in other healthcare settings to explore healthcare
      professional behaviour and to develop strategies to promote patient safety and
      effective professional practice.

PMID- 16885249
TI  - Overprescribing of lipid lowering agents.
AB  - BACKGROUND: Undertreatment of hyperlipidemia has received considerable attention.
      However, little is known about trends in overprescribing of lipid lowering
      agents. We examined these trends and their associations with physician, practice,
      and organisational factors. METHODS: 2034 physicians were surveyed twice:
      baseline (1996-7) and follow up (1998-9). On each occasion they were asked: "For
      what percentage of 50 year old men without other cardiac risk factors would you
      recommend an oral agent for total cholesterol of 240, LDL 150, and HDL 50 after 6
      months on a low cholesterol diet?" During the survey period the National
      Cholesterol Education Program guidelines did not recommend prescribing for these
      patients. Binomial and multinomial logistic regressions assessed baseline
      overprescribing and longitudinal changes in overprescribing, accounting for
      complex sampling. RESULTS: 39% of physicians recommended prescribing at baseline
      (round 1), increasing at follow up (round 2) to 51% (p < 0.001). Physicians who
      were more likely to overprescribe at baseline were less likely to be board
      certified (odds ratio (OR) 0.49, 95% confidence interval (CI) 0.38 to 0.63; p <
      0.001), were in solo or two-physician practices (OR 1.88, 95% CI 1.46 to 2.41; p
      < 0.001), had more revenue from Medicare (OR 1.10, 95% CI 1.03 to 1.17; p =
      0.004) or Medicaid (OR 1.09, 95% CI 1.01 to 1.18; p = 0.03), or were family
      physicians (OR 1.87, 95% CI 1.35 to 2.58; p < 0.001). Physicians with large
      increases in overprescibing were more likely than those with small increases in
      overprescribing to be international medical graduates (OR 2.09, 95% CI 1.20 to
      3.64; p = 0.011) and to spend more hours in patient care (OR 1.14, 95% CI 1.03 to
      1.26; p = 0.016). CONCLUSIONS: Overprescribing of lipid lowering agents is
      commonplace and increased. At baseline and longitudinally, overprescribing was
      primarily associated with physician and practice characteristics and not with
      organisational factors.

PMID- 16885251
TI  - Improving comfort and communication in the ICU: a practical new tool for
      palliative care performance measurement and feedback.
AB  - OBJECTIVE: To develop a practical set of measures for routine monitoring,
      performance feedback, and improvement in the quality of palliative care in the
      intensive care unit (ICU). DESIGN: Use of an interdisciplinary iterative process
      to create a prototype "bundle" of indicators within previously established
      domains of ICU palliative care quality; operationalization of indicators as
      specified measures; and pilot implementation to evaluate feasibility and baseline
      ICU performance. SETTING: The national Transformation of the Intensive Care Unit
      program developed in the United States by VHA Inc. PATIENTS: Critically ill
      patients in ICUs for 1, > 3, and > 5 days. MEASUREMENTS AND MAIN RESULTS:
      Palliative care processes including identification of patient preferences and
      decision making surrogates, communication between clinicians and
      patients/families, social and spiritual support, and pain assessment and
      management, as documented in medical records. Application is triggered by
      specified lengths of ICU stay. Pilot testing in 19 ICUs (review of > 100
      patients' records) documented feasibility, while revealing opportunities for
      quality improvement in clinician-patient/family communication and other key
      components of ICU palliative care. CONCLUSIONS: The new bundle of measures is a
      prototype for routine measurement of the quality of palliative care in the ICU.
      Further investigation is needed to confirm associations between measured
      processes and outcomes of importance to patients and families, as well as other
      aspects of validity.

PMID- 16885250
TI  - Time of day effects on the incidence of anesthetic adverse events.
AB  - BACKGROUND: We hypothesized that time of day of surgery would influence the
      incidence of anesthetic adverse events (AEs). METHODS: Clinical observations
      reported in a quality improvement database were categorized into different AEs
      that reflected (1) error, (2) harm, and (3) other AEs (error or harm could not be
      determined) and were analyzed for effects related to start hour of care. RESULTS:
      As expected, there were differences in the rate of AEs depending on start hour of
      care. Compared with a reference start hour of 7 am, other AEs were more frequent
      for cases starting during the 3 pm and 4 pm hours (p < 0.0001). Post hoc
      inspection of data revealed that the predicted probability increased from a low
      of 1.0% at 9 am to a high of 4.2% at 4 pm. The two most common event types (pain
      management and postoperative nausea and vomiting) may be primary determinants of
      these effects. CONCLUSIONS: Our results indicate that clinical outcomes may be
      different for patients anesthetized at the end of the work day compared with the
      beginning of the day. Although this may result from patient related factors,
      medical care delivery factors such as case load, fatigue, and care transitions
      may also be influencing the rate of anesthetic AEs for cases that start in the
      late afternoon.

PMID- 16885252
TI  - Role of medical students in preventing patient harm and enhancing patient safety.
AB  - BACKGROUND: Substantial efforts are focused on the high prevalence of patient
      harm due to medical errors and the mechanisms to prevent them. The potential role
      of the medical student as a valuable member of the team in preventing patient
      harm has, however, often been overlooked. METHODS: Four cases are presented from
      two US academic health centers in which medical students prevented or were in a
      position to prevent patient harm from occurring. The authors directly
      participated in each case. RESULTS: The types of harm prevented included averting
      non-sterile conditions, missing medications, mitigating exposure to highly
      contagious patients, and respecting patients' "do not resuscitate" requests.
      CONCLUSION: Medical students are often overlooked as valuable participants in
      ensuring patient safety. These cases show that medical students may be an
      untapped resource for medical error prevention. Medical students should be
      trained to recognize errors and to speak up when errors occur. Those supervising
      students should welcome and encourage students to actively communicate observed
      errors and near misses and should work to eliminate all intimidation by medical
      hierarchy that can prevent students from being safety advocates.

PMID- 16885253
TI  - A cross-cultural survey of residents' perceived barriers in
      questioning/challenging authority.
AB  - OBJECTIVES: To identify perceived barriers to residents' questioning or
      challenging their seniors, to determine how these barriers affect decisions, and
      to assess how these barriers differ across cultures. METHOD: A written
      questionnaire was administered to residents in teaching hospitals in the US and
      Japan to assess factors affecting residents' willingness to question or challenge
      their superiors. The responses were analyzed for statistical significance of
      differences between the two cultures and to determine the importance of issues
      affecting decisions. RESULTS: Questionnaires were completed by 175 US and 65
      Japanese residents, with an overall response rate of 71%. Trainees from both
      countries believe that questioning and challenging contribute to safety. The
      perceived importance of specific beliefs about the workplace differed across
      cultures in seven out of 22 questions. Residents' decisions to make a challenge
      were related to the relationships and perceived response of the superiors. There
      was no statistical difference between the US and Japanese residents in terms of
      the threshold for challenging their seniors. CONCLUSION: We have identified
      attributes of residents' beliefs of communication, including several cross
      cultural differences in the importance of values and issues affecting one's
      decision to question or challenge. In contrast, there was no difference in the
      threshold for challenging seniors by the Japanese and US residents studied.
      Changes in organizational and professional culture may be as important, if not
      more so, than national culture to encourage "speaking up". Residents should be
      encouraged to overcome barriers to challenging, and training programs should
      foster improved relationships and communication between trainers and trainees.

PMID- 16885254
TI  - Drugs to support smoking cessation in UK general practice: are evidence based
      guidelines being followed?
AB  - BACKGROUND: Prescribing drugs to support smoking cessation is one of the most
      cost effective interventions in primary care, but there is evidence they are
      underused. Little is known about how far guidelines have been adopted. AIMS: To
      examine the context in which nicotine replacement therapy (NRT) and bupropion are
      prescribed in UK general practice and whether guidelines are being followed.
      DESIGN: Patient questionnaire survey. SETTING: Twenty five general practices from
      the Trent Focus Collaborative Research Network in South Yorkshire and East
      Midlands, UK. METHODS: Participating practices posted a questionnaire to up to 40
      patients prescribed NRT and bupropion respectively in the previous 3-9 months.
      RESULTS: The response rate for people prescribed NRT was 44.7% (323/723) and for
      bupropion 42.5% (77/181). Patients reported initiating the prescription request
      in 258 cases (65%), whereas GPs were reported as suggesting it in 49 (12%),
      smoking cessation services (SCS) in 38 (10%), and practice nurses in 36 (9%). Of
      those who could recall the content of the consultation in which NRT or bupropion
      was prescribed, 191 (79%) reported receiving advice on treatment use and 209
      (68%) were encouraged to set a quit date. Follow up by SCS was recommended to 186
      (64%) and practice follow up was offered to 212 (63%), but 41 (15%) reported no
      offer of follow up support. CONCLUSIONS: The majority of patients reported
      receiving advice and follow up in line with guidelines. However, relatively few
      prescriptions were suggested by GPs or practice nurses and, in a significant
      minority of cases, neither follow up by the practice nor additional support from
      SCS was recommended. More active implementation of guidelines could increase the
      impact of general practice on the prevalence of smoking.

PMID- 16885255
TI  - Developing and implementing new safe practices: voluntary adoption through
      statewide collaboratives.
AB  - BACKGROUND: Disseminating new safe practices has proved challenging. In a
      statewide initiative we developed a framework for (1) selecting two safe
      practices, (2) developing operational details of implementation, (3) enlisting
      hospitals to participate, and (4) facilitating implementation. METHODS: Potential
      topics were selected by a multistep process to identify candidate practices,
      review the evidence for efficacy and feasibility, and then select them on the
      basis of importance, efficacy, feasibility, and impact. A multi-stakeholder
      advisory group representing all constituencies selected two practices:
      reconciling medications (RM) and communicating critical test results (CTR).
      Operational details and strategies for implementation were then developed for
      each practice using a consensus process of discipline stakeholders led by content
      experts. Hospital CEOs were solicited to participate by the Massachusetts
      Hospital Association which made the project a "flagship" initiative. A
      collaborative model was used to facilitate implementation, following the IHI
      Model for Improvement. In addition to providing exposure to content and method
      experts, we gave teams a "toolkit" containing recommendations, a change package,
      and implementation strategies. Each collaborative met four times over an 18 month
      period. Results were assessed using the IHI team assessment scale and surveys of
      teams and hospital leaders. RESULTS: Hospital participation rate was high with
      88% of hospitals participating in one or both collaboratives. Partial
      implementation of the practices was achieved by 50% of RM teams and 65% of CTR
      teams. Full implementation was achieved by 20% of teams for each. CONCLUSIONS:
      Major factors leading to hospital participation included the intrinsic appeal of
      the practices, access to experts, and the availability of implementation
      strategies. Team success was correlated with active engagement of a senior
      administrator, engagement of physicians, increased use of PDSA cycles, and
      attendance at collaborative meetings. The prior development of subpractices,
      recommendations and implementation strategies was essential for the hospital
      teams. These should be well worked out before hospitals are required to implement
      any guideline.

PMID- 16885257
TI  - Oliver Wendell Holmes MD 1809-94 and the logic of medicine.

PMID- 16885256
TI  - Getting the data right: information accuracy in pediatric emergency medicine.
AB  - OBJECTIVES: (1) To identify the extent to which information provided by parents
      in the pediatric emergency department (ED) can drive the assessment and
      categorization of data on allergies to medications, and (2) to identify errors
      related to the capture and documentation of allergy data at specific process
      level steps during ED care. METHODS: An observational study was conducted in a
      pediatric ED, combining direct observation at triage, a structured verbal
      interview with parents to ascertain a full allergy history related to
      medications, and chart abstraction. A comparative standard for the allergy
      history was established using parents' interview responses and existing
      guidelines for allergy. Errors associated with ED information management of
      allergy data were evaluated at five steps: (1) triage assessment, (2) treating
      physician's discussion with parent, (3) treating nurse's discussion with parent,
      (4) use of an allergy bracelet, and (5) documentation of allergy history on
      medication order sheets. RESULTS: 256 parent-child dyads were observed at triage;
      211/256 parents (82.4%) completed the structured verbal interview that served as
      the basis for the comparative standard (CS). Parents reported a total of 59
      medications as possible allergies; 56 (94.9%) were categorized as allergy or not
      based on the CS. Twenty eight of 48 patient cases were true allergies by
      guideline based assessment. Sensitivity of triage for detecting true medication
      allergy was 74.1% (95% confidence interval (CI) 53.7 to 88.9). Specificity of
      triage personnel for correctly determining that no allergy existed was 93.2% (95%
      CI 88.5 to 96.5). Physician and nursing care had performance gaps related to
      medication allergy in 10-25% of cases. CONCLUSIONS: There are significant gaps in
      the quality of information management regarding medication allergies in the
      pediatric ED.

PMID- 16885258
TI  - Production of a heterologous nonheme catalase by Lactobacillus casei: an
      efficient tool for removal of H2O2 and protection of Lactobacillus bulgaricus
      from oxidative stress in milk.
AB  - Lactic acid bacteria (LAB) are generally sensitive to H2O2, a compound that they
      can paradoxically produce themselves, as is the case for Lactobacillus
      bulgaricus. Lactobacillus plantarum ATCC 14431 is one of the very few LAB strains
      able to degrade H2O2 through the action of a nonheme, manganese-dependent
      catalase (hereafter called MnKat). The MnKat gene was expressed in three catalase
      deficient LAB species: L. bulgaricus ATCC 11842, Lactobacillus casei BL23, and
      Lactococcus lactis MG1363. While the protein could be detected in all
      heterologous hosts, enzyme activity was observed only in L. casei. This is
      probably due to the differences in the Mn contents of the cells, which are
      reportedly similar in L. plantarum and L. casei but at least 10- and 100-fold
      lower in Lactococcus lactis and L. bulgaricus, respectively. The expression of
      the MnKat gene in L. casei conferred enhanced oxidative stress resistance, as
      measured by an increase in the survival rate after exposure to H2O2, and improved
      long-term survival in aerated cultures. In mixtures of L. casei producing MnKat
      and L. bulgaricus, L. casei can eliminate H2O2 from the culture medium, thereby
      protecting both L. casei and L. bulgaricus from its deleterious effects.

PMID- 16885259
TI  - Peptide aMptD-mediated capture PCR for detection of Mycobacterium avium subsp.
      paratuberculosis in bulk milk samples.
AB  - A peptide-mediated capture PCR for the detection of Mycobacterium avium subsp.
      paratuberculosis in bulk milk samples was developed and characterized. Capture of
      the organism was performed using peptide aMptD, which had been shown to bind to
      the M. avium subsp. paratuberculosis MptD protein (J. Stratmann, B. Strommenger,
      R. Goethe, K. Dohmann, G. F. Gerlach, K. Stevenson, L. L. Li, Q. Zhang, V. Kapur,
      and T. J. Bull, Infect. Immun. 72:1265-1274, 2004). Consistent expression of the
      MptD receptor protein and binding of the aMptD ligand were demonstrated by
      capturing different Mycobacterium avium subsp. paratuberculosis type I and type
      II strains and subsequent PCR analysis using ISMav2-based primers. The analytical
      sensitivity of the method was determined to be 5 x 10(2) CFU ml(-1) for
      artificially contaminated milk. The specificity of aMptD binding was confirmed by
      culture and competitive capture assays, showing selective enrichment of M. avium
      subsp. paratuberculosis (at a concentration of 5 x 10(2) CFU ml(-1)) from samples
      containing 100- and 1,000-fold excesses of other mycobacterial species, including
      M. avium subsp. avium and M. avium subsp. hominissuis. The aMptD-mediated capture
      of M. avium subsp. paratuberculosis using paramagnetic beads, followed by
      culture, demonstrated the ability of this approach to capture viable target cells
      present in artificially contaminated milk. Surface plasmon resonance experiments
      revealed that the aMptD peptide is a high-affinity ligand with a calculated
      association rate constant of 9.28 x 10(3) and an association constant of 1.33 x
      10(9). The potential use of the method on untreated raw milk in the field was
      investigated by testing 423 bulk milk samples obtained from different dairy farms
      in Germany, 23 of which tested positive. Taken together, the results imply that
      the peptide-mediated capture PCR might present a suitable test for
      paratuberculosis screening of dairy herds, as it has an analytical sensitivity
      sufficient for detection of M. avium subsp. paratuberculosis in bulk milk samples
      under field conditions, relies on a defined and validated ligand-receptor
      interaction, and is adaptable to routine diagnostic laboratory automation.

PMID- 16885260
TI  - Evidence for geographic isolation and signs of endemism within a protistan
      morphospecies.
AB  - The possible existence of endemism among microorganisms resulting from and
      preserved by geographic isolation is one of the most controversial topics in
      microbial ecology. We isolated 31 strains of "Spumella-like" flagellates from
      remote sampling sites from all continents, including Antarctica. These and
      another 23 isolates from a former study were characterized morphologically and by
      small-subunit rRNA gene sequence analysis and tested for the maximum temperature
      tolerance. Only a minority of the Spumella morpho- and phylotypes from the
      geographically isolated Antarctic continent follow the worldwide trend of a
      linear correlation between ambient (air) temperature during strain isolation and
      heat tolerance of the isolates. A high percentage of the Antarctic isolates, but
      none of the isolates from locations on all other continents, were obligate
      psychrophilic, although some of the latter were isolated at low ambient
      temperatures. The drastic deviation of Antarctic representatives of Spumella from
      the global trend of temperature adaptation of this morphospecies provides strong
      evidence for geographic transport restriction of a microorganism; i.e., Antarctic
      protistan communities are less influenced by transport of protists to and from
      the Antarctic continent than by local adaptation, a subtle form of endemism.

PMID- 16885261
TI  - Salt, alone or in combination with sucrose, can improve the survival of
      Escherichia coli O157 (SERL 2) in model acidic sauces.
AB  - The commercial production of microbiologically safe and stable sauces containing
      acetic acid is guided by the Comite des Industries des Mayonnaises et Sauces
      Condimentaires de la Communaute Economique Europeenne's (CIMSCEE) code. The
      CIMSCEE safety value is calculated using a linear regression equation combining
      weighted contributions of pH and aqueous-phase concentrations of undissociated
      acetic acid, NaCl, and sugars. By implication, the CIMSCEE safety equation
      predicts that increasing concentrations of hurdles will always increase
      inactivation of the target pathogen. In this study, the time to achieve a 3-log10
      reduction of an acid-resistant, acid-adapted, Shiga toxin-producing Escherichia
      coli (STEC) O157 isolate was determined experimentally for 81 formulations at
      various pHs and acetic acid, NaCl, and sucrose concentrations in a broth model.
      The combinations were intended to simulate the aqueous phase of acidic sauces and
      dressings. Experimental data were fitted to the log logistic model to estimate
      the time to 3-log10 reduction (t3D). Comparison of fitted t3D estimates with
      CIMSCEE values showed agreement in predicting safety (as defined by CIMSCEE) for
      the majority of formulations. However, CIMSCEE safety predictions were "fail
      dangerous" for 13 of 81 formulations. Among these formulations and others, the
      observed E. coli t3D initially increased and then decreased with increasing
      osmolalities (NaCl and sucrose). Relative protection increased with exposure time
      where the protective effect of NaCl predominated. While commercial acidic sauces
      are not considered high-risk vehicles for STEC, interactions among hurdles that
      decrease their combined effectiveness are deserving of further investigation
      because they may reveal mechanisms of broader relevance in the inactivation of
      pathogens in foods.

PMID- 16885262
TI  - Resolution of distinct membrane-bound enzymes from Enterobacter cloacae SLD1a-1
      that are responsible for selective reduction of nitrate and selenate oxyanions.
AB  - Enterobacter cloacae SLD1a-1 is capable of reductive detoxification of selenate
      to elemental selenium under aerobic growth conditions. The initial reductive step
      is the two-electron reduction of selenate to selenite and is catalyzed by a
      molybdenum-dependent enzyme demonstrated previously to be located in the
      cytoplasmic membrane, with its active site facing the periplasmic compartment (C.
      A. Watts, H. Ridley, K. L. Condie, J. T. Leaver, D. J. Richardson, and C. S.
      Butler, FEMS Microbiol. Lett. 228:273-279, 2003). This study describes the
      purification of two distinct membrane-bound enzymes that reduce either nitrate or
      selenate oxyanions. The nitrate reductase is typical of the NAR-type family, with
      alpha and beta subunits of 140 kDa and 58 kDa, respectively. It is expressed
      predominantly under anaerobic conditions in the presence of nitrate, and while it
      readily reduces chlorate, it displays no selenate reductase activity in vitro.
      The selenate reductase is expressed under aerobic conditions and expressed poorly
      during anaerobic growth on nitrate. The enzyme is a heterotrimeric
      (alphabetagamma) complex with an apparent molecular mass of approximately 600
      kDa. The individual subunit sizes are approximately 100 kDa (alpha),
      approximately 55 kDa (beta), and approximately 36 kDa (gamma), with a predicted
      overall subunit composition of alpha3beta3gamma3. The selenate reductase contains
      molybdenum, heme, and nonheme iron as prosthetic constituents. Electronic
      absorption spectroscopy reveals the presence of a b-type cytochrome in the active
      complex. The apparent Km for selenate was determined to be approximately 2 mM,
      with an observed Vmax of 500 nmol SeO4(2-) min(-1) mg(-1) (kcat, approximately
      5.0 s(-1)). The enzyme also displays activity towards chlorate and bromate but
      has no nitrate reductase activity. These studies report the first purification
      and characterization of a membrane-bound selenate reductase.

PMID- 16885264
TI  - Measurement of biocolloid collision efficiencies for granular activated carbon by
      use of a two-layer filtration model.
AB  - Point-of-use filters containing granular activated carbon (GAC) are an effective
      method for removing certain chemicals from water, but their ability to remove
      bacteria and viruses has been relatively untested. Collision efficiencies (alpha)
      were determined using clean-bed filtration theory for two bacteria (Raoutella
      terrigena 33257 and Escherichia coli 25922), a bacteriophage (MS2), and latex
      microspheres for four GAC samples. These GAC samples had particle size
      distributions that were bimodal, but only a single particle diameter can be used
      in the filtration equation. Therefore, consistent with previous reports, we used
      a particle diameter based on the smallest diameter of the particles (derived from
      the projected areas of 10% of the smallest particles). The bacterial collision
      efficiencies calculated using the filtration model were high (0.8 < or = alpha <
      or = 4.9), indicating that GAC was an effective capture material. Collision
      efficiencies greater than unity reflect an underestimation of the collision
      frequency, likely as a result of particle roughness and wide GAC size
      distributions. The collision efficiencies for microspheres (0.7 < or = alpha < or
      = 3.5) were similar to those obtained for bacteria, suggesting that the
      microspheres were a reasonable surrogate for the bacteria. The bacteriophage
      collision efficiencies ranged from > or = 0.2 to < or = 0.4. The predicted levels
      of removal for 1-cm-thick carbon beds ranged from 0.8 to 3 log for the bacteria
      and from 0.3 to 1.0 log for the phage. These tests demonstrated that GAC can be
      an effective material for removal of bacteria and phage and that GAC particle
      size is a more important factor than relative stickiness for effective particle
      removal.

PMID- 16885263
TI  - Quantitative detection of the nosZ gene, encoding nitrous oxide reductase, and
      comparison of the abundances of 16S rRNA, narG, nirK, and nosZ genes in soils.
AB  - Nitrous oxide (N2O) is an important greenhouse gas in the troposphere controlling
      ozone concentration in the stratosphere through nitric oxide production. In order
      to quantify bacteria capable of N2O reduction, we developed a SYBR green
      quantitative real-time PCR assay targeting the nosZ gene encoding the catalytic
      subunit of the nitrous oxide reductase. Two independent sets of nosZ primers
      flanking the nosZ fragment previously used in diversity studies were designed and
      tested (K. Kloos, A. Mergel, C. Rosch, and H. Bothe, Aust. J. Plant Physiol.
      28:991-998, 2001). The utility of these real-time PCR assays was demonstrated by
      quantifying the nosZ gene present in six different soils. Detection limits were
      between 10(1) and 10(2) target molecules per reaction for all assays. Sequence
      analysis of 128 cloned quantitative PCR products confirmed the specificity of the
      designed primers. The abundance of nosZ genes ranged from 10(5) to 10(7) target
      copies g(-1) of dry soil, whereas genes for 16S rRNA were found at 10(8) to 10(9)
      target copies g(-1) of dry soil. The abundance of narG and nirK genes was within
      the upper and lower limits of the 16S rRNA and nosZ gene copy numbers. The two
      sets of nosZ primers gave similar gene copy numbers for all tested soils. The
      maximum abundance of nosZ and nirK relative to 16S rRNA was 5 to 6%, confirming
      the low proportion of denitrifiers to total bacteria in soils.

PMID- 16885265
TI  - SigmaB activation under environmental and energy stress conditions in Listeria
      monocytogenes.
AB  - To measure sigmaB activation in Listeria monocytogenes under environmental or
      energy stress conditions, quantitative reverse transcriptase PCR (TaqMan) was
      used to determine the levels of transcripts for the sigmaB -dependent opuCA and
      clpC genes in strains having null mutations in genes encoding regulator of sigma
      B proteins (rsbT and rsbV) and sigma B (sigB) and in the L. monocytogenes wild
      type 10403S strain under different stress conditions. The DeltasigB, DeltarsbT,
      and DeltarsbV strains previously exhibited increased hemolytic activities
      compared to the hemolytic activity of the wild-type strain; therefore, transcript
      levels for hly were also determined. RsbT, RsbV, and sigmaB were all required for
      opuCA expression during growth under carbon-limiting conditions or following
      exposure to pH 4.5, salt, ethanol, or the protonophore carbonyl cyanide m
      chlorophenylhydrazone (CCCP). Expression of clpC was RsbT, RsbV, and sigmaB
      dependent in the presence of CCCP but not under the other conditions. hly
      expression was not RsbT, RsbV, or sigmaB dependent in the presence of either CCCP
      or salt. opuCA transcript levels did not increase in the presence of rapidly
      lethal stresses (i.e., pH 2.5 or 13 mM cumene hydroperoxide) despite the enhanced
      survival of the wild type compared with the survival of the mutant strains under
      these conditions. These findings highlight the importance of complementing
      phenotypic characterizations with gene expression studies to identify direct and
      indirect effects of null mutations in regulatory genes, such as sigB. Overall,
      our data show that while sigmaB activation occurs through a single pathway under
      both environmental and energy stress conditions, regulation of expression of some
      stress response and virulence genes in the sigmaB regulon (e.g., clpC) appears to
      require networks involving multiple transcriptional regulators.

PMID- 16885267
TI  - Aggregative behavior of bacteria isolated from canine dental plaque.
AB  - Interbacterial adhesion of bacteria isolated from canine dental plaque was
      assessed by performing a visual coaggregation assay. Using conditions mimicking
      those likely to be encountered in vivo, the entire cultivable plaque microbiota
      from a single dog was assessed, and eight (6.7%) unique coaggregation
      interactions were detected for 120 crosses. Transmission electron microscopy was
      used to visualize several of the bacteria in isolation and as coaggregates, which
      revealed surface structures that may be involved in adhesion and coaggregation.
      The results of this study indicate that the prevalence of coaggregating pairs of
      dental plaque bacteria in dogs is similar to the prevalence of coaggregating
      pairs of dental plaque bacteria reported in humans. In addition, genera found in
      both hosts generally exhibited similar coaggregation reactions; however,
      autoaggregation was found to be more common among oral bacteria isolated from
      dogs.

PMID- 16885266
TI  - Kinetic analysis of bifidobacterial metabolism reveals a minor role for succinic
      acid in the regeneration of NAD+ through its growth-associated production.
AB  - Several strains belonging to the genus Bifidobacterium were tested to determine
      their abilities to produce succinic acid. Bifidobacterium longum strain BB536 and
      Bifidobacterium animalis subsp. lactis strain Bb 12 were kinetically analyzed in
      detail using in vitro fermentations to obtain more insight into the metabolism
      and production of succinic acid by bifidobacteria. Changes in end product
      formation in strains of Bifidobacterium could be related to the specific rate of
      sugar consumption. When the specific sugar consumption rate increased, relatively
      more lactic acid and less acetic acid, formic acid, and ethanol were produced,
      and vice versa. All Bifidobacterium strains tested produced small amounts of
      succinic acid; the concentrations were not more than a few millimolar. Succinic
      acid production was found to be associated with growth and stopped when the
      energy source was depleted. The production of succinic acid contributed to
      regeneration of a small part of the NAD+, in addition to the regeneration through
      the production of lactic acid and ethanol.

PMID- 16885268
TI  - Biodegradation of ether pollutants by Pseudonocardia sp. strain ENV478.
AB  - A bacterium designated Pseudonocardia sp. strain ENV478 was isolated by
      enrichment culturing on tetrahydrofuran (THF) and was screened to determine its
      ability to degrade a range of ether pollutants. After growth on THF, strain
      ENV478 degraded THF (63 mg/h/g total suspended solids [TSS]), 1,4-dioxane (21
      mg/h/g TSS), 1,3-dioxolane (19 mg/h/g TSS), bis-2-chloroethylether (BCEE) (12
      mg/h/g TSS), and methyl tert-butyl ether (MTBE) (9.1 mg/h/g TSS). Although the
      highest rates of 1,4-dioxane degradation occurred after growth on THF, strain
      ENV478 also degraded 1,4-dioxane after growth on sucrose, lactate, yeast extract,
      2-propanol, and propane, indicating that there was some level of constitutive
      degradative activity. The BCEE degradation rates were about threefold higher
      after growth on propane (32 mg/h/g TSS) than after growth on THF, and MTBE
      degradation resulted in accumulation of tert-butyl alcohol. Degradation of 1,4
      dioxane resulted in accumulation of 2-hydroxyethoxyacetic acid (2HEAA). Despite
      its inability to grow on 1,4-dioxane, strain ENV478 degraded this compound for >
      80 days in aquifer microcosms. Our results suggest that the inability of strain
      ENV478 and possibly other THF-degrading bacteria to grow on 1,4-dioxane is
      related to their inability to efficiently metabolize the 1,4-dioxane degradation
      product 2HEAA but that strain ENV478 may nonetheless be useful as a biocatalyst
      for remediating 1,4-dioxane-contaminated aquifers.

PMID- 16885269
TI  - Multiple microfermentor battery: a versatile tool for use with automated parallel
      cultures of microorganisms producing recombinant proteins and for optimization of
      cultivation protocols.
AB  - A multiple microfermentor battery was designed for high-throughput recombinant
      protein production in Escherichia coli. This novel system comprises eight aerated
      glass reactors with a working volume of 80 ml and a moving external optical
      sensor for measuring optical densities at 600 nm (OD600) ranging from 0.05 to 100
      online. Each reactor can be fitted with miniature probes to monitor temperature,
      dissolved oxygen (DO), and pH. Independent temperature regulation for each vessel
      is obtained with heating/cooling Peltier devices. Data from pH, DO, and turbidity
      sensors are collected on a FieldPoint (National Instruments) I/O interface and
      are processed and recorded by a LabVIEW program on a personal computer, which
      enables feedback control of the culture parameters. A high-density medium
      formulation was designed, which enabled us to grow E. coli to OD600 up to 100 in
      batch cultures with oxygen-enriched aeration. Accordingly, the biomass and the
      amount of recombinant protein produced in a 70-ml culture were at least
      equivalent to the biomass and the amount of recombinant protein obtained in a
      Fernbach flask with 1 liter of conventional medium. Thus, the microfermentor
      battery appears to be well suited for automated parallel cultures and process
      optimization, such as that needed for structural genomics projects.

PMID- 16885270
TI  - Molecular profiling of the Clostridium leptum subgroup in human fecal microflora
      by PCR-denaturing gradient gel electrophoresis and clone library analysis.
AB  - A group-specific PCR-based denaturing gradient gel electrophoresis (DGGE) method
      was developed and combined with group-specific clone library analysis to
      investigate the diversity of the Clostridium leptum subgroup in human feces. PCR
      products (length, 239 bp) were amplified using C. leptum cluster-specific primers
      and were well separated by DGGE. The DGGE patterns of fecal amplicons from 11
      human individuals revealed host-specific profiles; the patterns for fecal samples
      collected from a child for 3 years demonstrated the structural succession of the
      population in the first 2 years and its stability in the third year. A clone
      library was constructed with 100 clones consisting of 1,143-bp inserts of 16S
      rRNA gene fragments that were amplified from one adult fecal DNA with one forward
      universal bacterial primer and one reverse group-specific primer. Eighty-six of
      the clones produced the 239-bp C. leptum cluster-specific amplicons, and the
      remaining 14 clones did not produce these amplicons but still phylogenetically
      belong to the subgroup. Sixty-four percent of the clones were related to
      Faecalibacterium prausnitzii (similarity, 97 to 99%), 6% were related to
      Subdoligranulum variabile (similarity, approximately 99%), 2% were related to
      butyrate-producing bacterium A2-207 (similarity, 99%), and 28% were not
      identified at the species level. The identities of most bands in the DGGE
      profiles for the same adult were determined by comigration analysis with the 86
      clones that harbored the 239-bp group-specific fragments. Our results suggest
      that DGGE combined with clone library analysis is an effective technique for
      monitoring and analyzing the composition of this important population in the
      human gut flora.

PMID- 16885271
TI  - Deletion mutations caused by DNA strand slippage in Acinetobacter baylyi.
AB  - Short nucleotide sequence repetitions in DNA can provide selective benefits and
      also can be a source of genetic instability arising from deletions guided by
      pairing between misaligned strands. These findings raise the question of how the
      frequency of deletion mutations is influenced by the length of sequence
      repetitions and by the distance between them. An experimental approach to this
      question was presented by the heat-sensitive phenotype conferred by pcaG1102, a
      30-bp deletion in one of the structural genes for Acinetobacter baylyi
      protocatechuate 3,4-dioxygenase, which is required for growth with quinate. The
      original pcaG1102 deletion appears to have been guided by pairing between slipped
      DNA strands from nearby repeated sequences in wild-type pcaG. Placement of an in
      phase termination codon between the repeated sequences in pcaG prevents growth
      with quinate and permits selection of sequence-guided deletions that excise the
      codon and permit quinate to be used as a growth substrate at room temperature.
      Natural transformation facilitated introduction of 68 different variants of the
      wild-type repeat structure within pcaG into the A. baylyi chromosome, and the
      frequency of deletion between the repetitions was determined with a novel method,
      precision plating. The deletion frequency increases with repeat length, decreases
      with the distance between repeats, and requires a minimum amount of similarity to
      occur at measurable rates. Deletions occurred in a recA-deficient background.
      Their frequency was unaffected by deficiencies in mutS and was increased by
      inactivation of recG.

PMID- 16885272
TI  - Comparison of rRNA and polar-lipid-derived fatty acid biomarkers for assessment
      of 13C-substrate incorporation by microorganisms in marine sediments.
AB  - We determined whether a recently developed method to isolate specific small
      subunit (SSU) rRNAs can be used in 13C-labeling studies to directly link
      community structure and function in natural ecosystems. Replicate North Sea
      sediment cores were incubated at the in situ temperature following addition of
      13C-labeled acetate, propionate, amino acids, or glucose. Eukaryotic and
      bacterial SSU rRNAs were separated from total RNA by means of biotin-labeled
      oligonucleotide probes and streptavidin-coated paramagnetic beads, and the 13C
      content of the isolated rRNA was determined by elemental analysis-isotope ratio
      mass spectrometry. The SSU rRNA yield with the bead-capture protocol was improved
      by using helper probes. Incorporation of label into bacterial SSU rRNA was
      detectable after 2 h of incubation. The labeling was always much greater in
      bacterial SSU rRNA than in eukaryotic SSU rRNA, suggesting that bacteria were the
      main consumers of the 13C-labeled compounds. Similar results were obtained with
      the 13C-labeled polar-lipid-derived fatty acid (PLFA) approach, except that more
      label was detected in bacterial PLFA than in bacterial SSU rRNA. This may be
      attributable to the generally slow growth of sediment microbial populations,
      which results in low ribosome synthesis rates and relatively few ribosomes per
      cell. We discuss possible ways to improve the probe-capture protocol and the
      sensitivity of the 13C analysis of the captured SSU rRNA.

PMID- 16885274
TI  - The Bacillus subtilis nrdEF genes, encoding a class Ib ribonucleotide reductase,
      are essential for aerobic and anaerobic growth.
AB  - Ribonucleotide reductases (RNRs) are essential for the biosynthesis of the
      deoxyribonucleoside triphosphates of DNA. Recently, it was proposed that
      externally supplied deoxyribonucleosides or DNA is required for the growth of
      Bacillus subtilis under strict anaerobic conditions (M. J. Folmsbee, M. J.
      McInerney, and D. P. Nagle, Appl. Environ. Microbiol. 70:5252-5257, 2004).
      Cultivation of B. subtilis on minimal medium in the presence of oxygen indicators
      in combination with oxygen electrode measurements and viable cell counting
      demonstrated that growth occurred under strict anaerobic conditions in the
      absence of externally supplied deoxyribonucleosides. The nrdEF genes encode the
      only obvious RNR in B. subtilis. A temperature-sensitive nrdE mutant failed to
      grow under aerobic and anaerobic conditions, indicating that this oxygen
      dependent class I RNR has an essential role under both growth conditions. Aerobic
      growth and anaerobic growth of the nrdE mutant were rescued by addition of
      deoxynucleotides. The nrd locus consists of an nrdI-nrdE-nrdF-ymaB operon. The 5'
      end of the corresponding mRNA revealed transcriptional start sites 45 and 48 bp
      upstream of the translational start of nrdI. Anaerobic transcription of the
      operon was found to be dependent on the presence of intact genes for the ResDE
      two-component redox regulatory system. Two potential ResD binding sites were
      identified approximately 62 bp (site A) and 50 bp (site B) upstream of the
      transcriptional start sites by a bioinformatic approach. Only mutation of site B
      eliminated nrd expression. Aerobic transcription was ResDE independent but
      required additional promoter elements localized between 88 and 275 bp upstream of
      the transcriptional start.

PMID- 16885273
TI  - Bacteria associated with mucus and tissues of the coral Oculina patagonica in
      summer and winter.
AB  - The relative abundance of bacteria in the mucus and crushed tissue of the
      Mediterranean coral Oculina patagonica was determined by analyses of the 16S rRNA
      genes of isolated colonies and from a 16S rRNA clone library of extracted DNA. By
      SYBR gold staining, the numbers of bacteria in mucus and tissue samples were 6.2
      x 10(7) and 8.3 x 10(8)/cm2 of coral surface, respectively, 99.8% of which failed
      to produce colonies on Marine Agar. From analysis of mucus DNA, the most-abundant
      bacterium was Vibrio splendidus, representing 68% and 50% of the clones from the
      winter and summer, respectively. After removal of mucus from coral by
      centrifugation, analyses of DNA from the crushed tissue revealed a large
      diversity of bacteria, with Vibrio species representing less than 5% of the
      clones. The most-abundant culturable bacteria were a Pseudomonas sp. (8 to 14%)
      and two different alpha-proteobacteria (6 to 18%). Out of a total 1,088 16S rRNA
      genes sequenced, 400 different operational taxonomic units were identified (>
      99.5% identity). Of these, 295 were novel (< 99% identical to any sequences in
      the GenBank database). This study provides a comprehensive database for future
      examinations of changes in the bacterial community during bleaching events.

PMID- 16885275
TI  - Engineering of promoter replacement cassettes for fine-tuning of gene expression
      in Saccharomyces cerevisiae.
AB  - The strong overexpression or complete deletion of a gene gives only limited
      information about its control over a certain phenotype or pathway. Gene function
      studies based on these methods are therefore incomplete. To effect facile
      manipulation of gene expression across a full continuum of possible expression
      levels, we recently created a library of mutant promoters. Here, we provide the
      detailed characterization of our yeast promoter collection comprising 11 mutants
      of the strong constitutive Saccharomyces cerevisiae TEF1 promoter. The activities
      of the mutant promoters range between about 8% and 120% of the activity of the
      unmutated TEF1 promoter. The differences in reporter gene expression in the 11
      mutants were independent of the carbon source used, and real-time PCR confirmed
      that these differences were due to varying levels of transcription (i.e., caused
      by varying promoter strengths). In addition to a CEN/ARS plasmid-based promoter
      collection, we also created promoter replacement cassettes. They enable genomic
      integration of our mutant promoter collection upstream of any given yeast gene,
      allowing detailed genotype-phenotype characterizations. To illustrate the utility
      of the method, the GPD1 promoter of S. cerevisiae was replaced by five TEF1
      promoter mutants of different strengths, which allowed analysis of the impact of
      glycerol 3-phosphate dehydrogenase activity on the glycerol yield.

PMID- 16885276
TI  - Virus-bacterium interactions in water and sediment of West African inland aquatic
      systems.
AB  - The ecology of virioplankton in tropical aquatic ecosystems is poorly documented,
      and in particular, there are no references concerning African continental waters
      in the literature. In this study, we examined virus-bacterium interactions in the
      pelagic and benthic zones of seven contrasting shallow inland waters in Senegal,
      including one hypersaline lake. SYBR Gold-stained samples revealed that in the
      surface layers of the sites, the numbers of viruses were in the same range as the
      numbers of viruses reported previously for productive temperate systems. Despite
      high bacterial production rates, the percentages of visibly infected cells (as
      determined by transmission electron microscopy) were similar to the lowest
      percentages (range, 0.3 to 1.1%; mean, 0.5%) found previously at pelagic
      freshwater or marine sites, presumably because of the local environmental and
      climatic conditions. Since the percentages of lysogenic bacteria were
      consistently less than 8% for pelagic and benthic samples, lysogeny did not
      appear to be a dominant strategy for virus propagation at these sites. In the
      benthic samples, viruses were highly concentrated, but paradoxically, no bacteria
      were visibly infected. This suggests that sediment provides good conditions for
      virus preservation but ironically is an unfavorable environment for
      proliferation. In addition, given the comparable size distributions of viruses in
      the water and sediment samples, our results support the paradigm that aquatic
      viruses are ubiquitous and may have moved between the two compartments of the
      shallow systems examined. Overall, this study provides additional information
      about the relevance of viruses in tropical areas and indicates that the intensity
      of virus-bacterium interactions in benthic habitats may lower than the intensity
      in the adjacent bodies of water.

PMID- 16885277
TI  - Unlocking Streptomyces spp. for use as sustainable industrial production
      platforms by morphological engineering.
AB  - Filamentous actinomycetes are commercially widely used as producers of natural
      products (in particular antibiotics) and of industrial enzymes. However, the
      mycelial lifestyle of actinomycetes, resulting in highly viscous broths and
      unfavorable pellet formation, has been a major bottleneck in their
      commercialization. Here we describe the successful morphological engineering of
      industrially important streptomycetes through controlled expression of the
      morphogene ssgA. This led to improved growth of many industrial and reference
      streptomycetes, with fragmentation of the mycelial clumps resulting in
      significantly enhanced growth rates in batch fermentations of Streptomyces
      coelicolor and Streptomyces lividans. Product formation was also stimulated, with
      a twofold increase in yield of enzyme production by S. lividans. We anticipate
      that the use of the presented methodology will make actinomycetes significantly
      more attractive as industrial and sustainable production hosts.

PMID- 16885278
TI  - Screening for and identification of starch-, amylopectin-, and pullulan-degrading
      activities in bifidobacterial strains.
AB  - Forty-two bifidobacterial strains were screened for alpha-amylase and/or
      pullulanase activity by investigating their capacities to utilize starch,
      amylopectin, or pullulan. Of the 42 bifidobacterial strains tested, 19 were
      capable of degrading potato starch. Of these 19 strains, 11 were able to degrade
      starch and amylopectin, as well as pullulan. These 11 strains, which were shown
      to produce extracellular starch-degrading activities, included 5 strains of
      Bifidobacterium breve, 1 B. dentium strain, 1 B. infantis strain, 3 strains of B.
      pseudolongum, and 1 strain of B. thermophilum. Quantitative and qualitative
      enzyme activities were determined by measuring the concentrations of released
      reducing sugars and by high-performance thin-layer chromatography, respectively.
      These analyses confirmed both the inducible nature and the extracellular nature
      of the starch- and pullulan-degrading enzyme activities and showed that the five
      B. breve strains produced an activity that is consistent with type II pullulanase
      (amylopullulanase) activity, while the remaining six strains produced an activity
      with properties that resemble those of type III pullulan hydrolase.

PMID- 16885279
TI  - Occurrence of Cryptosporidium oocysts and Giardia cysts in sewage in Norway.
AB  - Samples of sewage influent from 40 sewage treatment works (STW) throughout Norway
      were examined for Cryptosporidium oocysts and Giardia duodenalis cysts. Both
      parasites were detected frequently (80% of STW were Cryptosporidium positive; 93%
      of STW were Giardia positive) and at maximum concentrations of > 20,000
      parasites/liter. The data suggest giardiasis is more widespread, and/or occurs
      with greater infection intensity, than cryptosporidiosis in Norway. STW serving
      higher person equivalents were more likely to be positive and had higher parasite
      concentrations. Parasite concentrations were used to estimate the proportion of
      contributing populations that could be clinically infected. For Cryptosporidium,
      the highest estimates were up to 5 per 100,000 individuals for two populations in
      eastern Norway. For Giardia, the highest estimate was 40 infected per 100,000
      persons (approximately five times the usual national annual average) contributing
      to an STW in western Norway. As this population experienced a large waterborne
      giardiasis outbreak 6 months after sampling, it can be speculated that regular
      challenge with Giardia may occur here. Most Giardia isolates in sewage influent
      were assemblage A, although some assemblage B isolates were detected. There was
      substantial heterogeneity, but most samples contained isolates similar to
      genotype A3. Removal efficiencies at two STW with secondary treatment processes
      were estimated to be approximately 50% for Cryptosporidium and > 80% for Giardia.
      An STW with minimal treatment had negligible removal of both parasites. Many STW
      in Norway have minimal treatment and discharge effluent into rivers and lakes,
      thus, risk of contamination of water courses by Cryptosporidium and Giardia is
      considerable.

PMID- 16885280
TI  - Forensic application of microbiological culture analysis to identify mail
      intentionally contaminated with Bacillus anthracis spores.
AB  - The discovery of a letter intentionally filled with dried Bacillus anthracis
      spores in the office of a United States senator prompted the collection and
      quarantine of all mail in congressional buildings. This mail was subsequently
      searched for additional intentionally contaminated letters. A microbiological
      sampling strategy was used to locate heavy contamination within the 642 separate
      plastic bags containing the mail. Swab sampling identified 20 bags for manual and
      visual examination. Air sampling within the 20 bags indicated that one bag was
      orders of magnitude more contaminated than all the others. This bag contained a
      letter addressed to Senator Patrick Leahy that had been loaded with dried B.
      anthracis spores. Microbiological sampling of compartmentalized batches of mail
      proved to be efficient and relatively safe. Efficiency was increased by
      inoculating culture media in the hot zone rather than transferring swab samples
      to a laboratory for inoculation. All mail sampling was complete within 4 days
      with minimal contamination of the sampling environment or personnel. However,
      physically handling the intentionally contaminated letter proved to be
      exceptionally hazardous, as did sorting of cross-contaminated mail, which
      resulted in generation of hazardous aerosol and extensive contamination of
      protective clothing. Nearly 8 x 10(6) CFU was removed from the most highly cross
      contaminated piece of mail found. Tracking data indicated that this and other
      heavily contaminated envelopes had been processed through the same mail sorting
      equipment as, and within 1 s of, two intentionally contaminated letters.

PMID- 16885282
TI  - Analyses of Cry1Ab binding in resistant and susceptible strains of the European
      corn borer, Ostrinia nubilalis (Hubner) (Lepidoptera: Crambidae).
AB  - Cry1Ab toxin binding analysis was performed to determine whether resistance in
      laboratory-selected Ostrinia nubilalis strains is associated with target site
      alteration. Brush border membrane vesicles were prepared using dissected midguts
      from late instars of susceptible and resistant strains (Europe-R and RSTT) of O.
      nubilalis. Immunoblot analysis indicated that three different proteins bound to
      Cry1Ab toxin and were recognized by an anticadherin serum. In a comparison of
      resistant and susceptible strains, reduced Cry1Ab binding was apparent for all
      three bands corresponding to cadherin-like proteins in the Europe-R strain, while
      reduced binding was apparent in only one band for the RSTT strain. Real-time
      analysis of Cry1Ab binding to gut receptors using surface plasmon resonance
      suggested slight differences in affinity in both resistant strains. Additional
      binding analysis was conducted using 125I-labeled Cry1Ab, Cry1Ac, and Cry1Aa.
      Slight differences were again observed between the resistant and susceptible
      strains for Cry1Ab binding. However, when binding of 125I-labeled Cry1Aa was
      tested, a 10-fold reduction in the concentration of binding sites was observed in
      the Europe-R strain. Expression of the O. nubilalis cadherin gene was similar in
      both the resistant and susceptible strains and did not account for differences in
      binding. In combination, the results of the present work suggest that differences
      in susceptibility to Cry1A toxins in the Europe-R strain of O. nubilalis are
      associated with altered receptor binding, although the precise nature of this
      mechanism is still uncertain.

PMID- 16885281
TI  - Improved in situ hybridization efficiency with locked-nucleic-acid-incorporated
      DNA probes.
AB  - Low signal intensity due to poor probe hybridization efficiency is one of the
      major drawbacks of rRNA-targeted in situ hybridization. There are two major
      factors affecting the hybridization efficiency: probe accessibility and affinity
      to the targeted rRNA molecules. In this study, we demonstrate remarkable
      improvement in in situ hybridization efficiency by applying locked-nucleic-acid
      (LNA)-incorporated oligodeoxynucleotide probes (LNA/DNA probes) without
      compromising specificity. Fluorescently labeled LNA/DNA probes with two to four
      LNA substitutions exhibited strong fluorescence intensities equal to or greater
      than that of probe Eub338, although these probes did not show bright signals when
      they were synthesized as DNA probes; for example, the fluorescence intensity of
      probe Eco468 increased by 22-fold after three LNA bases were substituted for DNA
      bases. Dissociation profiles of the probes revealed that the dissociation
      temperature was directly related to the number of LNA substitutions and the
      fluorescence intensity. These results suggest that the introduction of LNA
      residues in DNA probes will be a useful approach for effectively enhancing probe
      hybridization efficiency.

PMID- 16885283
TI  - Eukaryotic community distribution and its relationship to water physicochemical
      parameters in an extreme acidic environment, Rio Tinto (southwestern Spain).
AB  - The correlation between water physicochemical parameters and eukaryotic benthic
      composition was examined in Rio Tinto. Principal component analysis showed a high
      inverse relationship between pH and most of the heavy metals analyzed as well as
      Dunaliella sp., while Chlamydomonas sp. abundance was positively related. Zn, Cu,
      and Ni clustered together and showed a strong inverse correlation with the
      diversity coefficient and most of the species analyzed. These eukaryotic
      communities seem to be more influenced by the presence of heavy metals than by
      the pH.

PMID- 16885284
TI  - Genetic diversity of Borrelia burgdorferi sensu stricto in Peromyscus leucopus,
      the primary reservoir of Lyme disease in a region of endemicity in southern
      Maryland.
AB  - In the north central and northeastern United States, Borrelia burgdorferi sensu
      stricto, the etiologic agent of Lyme disease (LD), is maintained in an enzootic
      cycle between the vector, Ixodes scapularis, and the primary reservoir host,
      Peromyscus leucopus. Genetic diversity of the pathogen based on sequencing of two
      plasmid-located genes, those for outer surface protein A (ospA) and outer surface
      protein C (ospC), has been examined in both tick and human specimens at local,
      regional, and worldwide population scales. Additionally, previous studies have
      only been conducted with tick or human specimens at the local population level in
      areas with high LD transmission rates. This study examined the genetic diversity
      of circulating borreliae in the reservoir population from a large region of the
      western coastal plains of southern Maryland, where moderate numbers of human LD
      cases are reported. Six ospA mobility classes, including two that were not
      previously described, and eight ospC groups were found among the P. leucopus
      samples. Twenty-five percent of all specimens were infected with more than one
      ospA or ospC variant. The frequency distribution of variants was homogeneous,
      both locally and spatially. The spirochete diversity found in Maryland was not as
      high as that observed among northern tick populations, yet similar genotypes were
      observed in both populations. These results also show that mice are important for
      maintaining Borrelia variants, even rare variants, and that reservoir populations
      should therefore be considered when assessing the diversity of B. burgdorferi.

PMID- 16885285
TI  - Identification of bacterial micropredators distinctively active in a soil
      microbial food web.
AB  - The understanding of microbial interactions and trophic networks is a
      prerequisite for the elucidation of the turnover and transformation of organic
      materials in soils. To elucidate the incorporation of biomass carbon into a soil
      microbial food web, we added 13C-labeled Escherichia coli biomass to an
      agricultural soil and identified those indigenous microbes that were specifically
      active in its mineralization and carbon sequestration. rRNA stable isotope
      probing (SIP) revealed that uncultivated relatives of distinct groups of gliding
      bacterial micropredators (Lysobacter spp., Myxococcales, and the Bacteroidetes)
      lead carbon sequestration and mineralization from the added biomass. In addition,
      fungal populations within the Microascaceae were shown to respond to the added
      biomass after only 1 h of incubation and were thus surprisingly reactive to
      degradable labile carbon. This RNA-SIP study identifies indigenous microbes
      specifically active in the transformation of a nondefined complex carbon source,
      bacterial biomass, directly in a soil ecosystem.

PMID- 16885286
TI  - Real-time detection of noroviruses in surface water by use of a broadly reactive
      nucleic acid sequence-based amplification assay.
AB  - Noroviruses are the most common agents causing outbreaks of viral
      gastroenteritis. Outbreaks originating from contaminated drinking water and from
      recreational waters have been described. Due to a lack of cell culture systems,
      noroviruses are detected mostly by molecular methods. Molecular detection assays
      for viruses in water are often repressed by inhibitory factors present in the
      environment, like humic acids and heavy metals. To study the effect of
      environmental inhibitors on the performance of nucleic acid sequence-based
      amplification (NASBA), we developed a real-time norovirus NASBA targeting part of
      the RNA-dependent RNA polymerase (RdRp) gene. Specificity of the assay was
      studied with 33 divergent clones that contained part of the targeted RdRp gene of
      noroviruses from 15 different genogroups. Viral RNA originated from commercial
      oysters, surface waters, and sewage treatment plants in The Netherlands. Ninety
      seven percent of the clones derived from human noroviruses were detected by real
      time NASBA. Two clones containing animal noroviruses were not detected by NASBA.
      We compared the norovirus detection by real-time NASBA with that by conventional
      reverse transcriptase PCR (RT-PCR) with large-volume river water samples and
      found that inhibitory factors of RT-PCR had little or no effect on the
      performance of the norovirus NASBA. This consequently resulted in a higher
      sensitivity of the NASBA assay than of the RT-PCR. We show that by combining an
      efficient RNA extraction method with real-time NASBA the sensitivity of norovirus
      detection in water samples increased at least 100 times, which consequently has
      implications for the outcome of the infectious risk assessment.

PMID- 16885288
TI  - Hyperthermophilic DNA methyltransferase M.PabI from the archaeon Pyrococcus
      abyssi.
AB  - Genome sequence comparisons among multiple species of Pyrococcus, a
      hyperthermophilic archaeon, revealed a linkage between a putative restriction
      modification gene complex and several large genome polymorphisms/rearrangements.
      From a region apparently inserted into the Pyrococcus abyssi genome, a
      hyperthermoresistant restriction enzyme [PabI; 5'-(GTA/C)] with a novel structure
      was discovered. In the present work, the neighboring methyltransferase homologue,
      M.PabI, was characterized. Its N-terminal half showed high similarities to the M
      subunit of type I systems and a modification enzyme of an atypical type II
      system, M.AhdI, while its C-terminal half showed high similarity to the S subunit
      of type I systems. M.PabI expressed within Escherichia coli protected PabI sites
      from RsaI, a PabI isoschizomer. M.PabI, purified following overexpression, was
      shown to generate 5'-GTm6AC, which provides protection against PabI digestion.
      M.PabI was found to be highly thermophilic; it showed methylation at 95 degrees C
      and retained at least half the activity after 9 min at 95 degrees C. This
      hyperthermophilicity allowed us to obtain activation energy and other
      thermodynamic parameters for the first time for any DNA methyltransferases. We
      also determined the kinetic parameters of kcat, Km, DNA, and Km, AdoMet. The
      activity of M.PabI was optimal at a slightly acidic pH and at an NaCl
      concentration of 200 to 500 mM and was inhibited by Zn2+ but not by Mg2+, Ca2+,
      or Mn2+. These and previous results suggest that this unique methyltransferase
      and PabI constitute a type II restriction-modification gene complex that inserted
      into the P. abyssi genome relatively recently. As the most thermophilic of all
      the characterized DNA methyltransferases, M.PabI may help in the analysis of DNA
      methylation and its application to DNA engineering.

PMID- 16885287
TI  - Application of bacteriophages to control intestinal Escherichia coli O157:H7
      levels in ruminants.
AB  - A previously characterized O157-specific lytic bacteriophage KH1 and a newly
      isolated phage designated SH1 were tested, alone or in combination, for reducing
      intestinal Escherichia coli O157:H7 in animals. Oral treatment with phage KH1 did
      not reduce the intestinal E. coli O157:H7 in sheep. Phage SH1 formed clear and
      relatively larger plaques on lawns of all 12 E. coli O157:H7 isolates tested and
      had a broader host range than phage KH1, lysing O55:H6 and 18 of 120 non-O157 E.
      coli isolates tested. In vitro, mucin or bovine mucus did not inhibit bacterial
      lysis by phage SH1 or KH1. A phage treatment protocol was optimized using a mouse
      model of E. coli O157:H7 intestinal carriage. Oral treatment with SH1 or a
      mixture of SH1 and KH1 at phage/bacterium ratios > or = 10(2) terminated the
      presence of fecal E. coli O157:H7 within 2 to 6 days after phage treatment.
      Untreated control mice remained culture positive for >10 days. To optimize
      bacterial carriage and phage delivery in cattle, E. coli O157:H7 was applied
      rectally to Holstein steers 7 days before the administration of 10(10) PFU SH1
      and KH1. Phages were applied directly to the rectoanal junction mucosa at
      phage/bacterium ratios calculated to be > or = 10(2). In addition, phages were
      maintained at 10(6) PFU/ml in the drinking water of the phage treatment group.
      This phage therapy reduced the average number of E. coli O157:H7 CFU among phage
      treated steers compared to control steers (P < 0.05); however, it did not
      eliminate the bacteria from the majority of steers.

PMID- 16885289
TI  - Intraspecific genotypic characterization of Lactobacillus rhamnosus strains
      intended for probiotic use and isolates of human origin.
AB  - A set of 118 strains of the species Lactobacillus rhamnosus was collected,
      including probiotic strains, research strains with potential probiotic
      properties, food starter cultures, and human isolates. The majority of the
      strains were collected from companies, hospitals, or culture collections or were
      obtained after contacting authors who reported clinical case studies in the
      literature. The present work aimed to reveal the genotypic relationships between
      strains of these diverse sources. All strains were initially investigated using
      fluorescent amplified fragment length polymorphism (FAFLP) with three different
      primer combinations. Numerical analysis of FAFLP data allowed (i) confirmation of
      the identification of all strains as members of L. rhamnosus and (ii) delineation
      of seven stable intraspecific FAFLP clusters. Most of these clusters contained
      both (potentially) probiotic strains and isolates of human origin. For each of
      the clusters, strains of different sources were selected for pulsed-field gel
      electrophoresis (PFGE) of macrorestriction fragments obtained with the enzymes
      NotI and AscI. Analysis of PFGE data indicated that (i) some (potentially)
      probiotic strains were indistinguishable from other probiotic strains, suggesting
      that several companies may use duplicate cultures of the same probiotic strain,
      and (ii) in a number of cases human isolates from sterile body sites were
      indistinguishable from a particular probiotic strain, suggesting that some of
      these isolates may be reisolations of commercial strains.

PMID- 16885291
TI  - Multiple-subunit genes of the aromatic-ring-hydroxylating dioxygenase play an
      active role in biphenyl and polychlorinated biphenyl degradation in Rhodococcus
      sp. strain RHA1.
AB  - A gram-positive strong polychlorinated biphenyl (PCB) degrader, Rhodococcus sp.
      strain RHA1, can degrade PCBs by cometabolism with biphenyl or ethylbenzene. In
      RHA1, three sets of aromatic-ring-hydroxylating dioxygenase genes are induced by
      biphenyl. The large and small subunits of their terminal dioxygenase components
      are encoded by bphA1 and bphA2, etbA1 and etbA2, and ebdA1 and ebdA2,
      respectively, and the deduced amino acid sequences of etbA1 and etbA2 are
      identical to those of ebdA1 and ebdA2, respectively. In this study, we examined
      the involvement of the respective subunit genes in biphenyl/PCB degradation by
      RHA1. Reverse transcription-PCR and two-dimensional polyacrylamide gel
      electrophoresis analyses indicated the induction of RNA and protein products of
      etbA1 and ebdA1 by biphenyl. Single- and double-disruption mutants of etbA1,
      ebdA1, and bphA1 were constructed by insertional inactivation. The 4
      chlorobiphenyl (4-CB) degradation activities of all the mutants were lower than
      that of RHA1. The results indicated that all of these genes are involved in
      biphenyl/PCB degradation. Furthermore, we constructed disruption mutants of ebdA3
      and bphA3, encoding ferredoxin, and etbA4, encoding ferredoxin reductase
      components. The 4-CB degradation activities of these mutants were also lower than
      that of RHA1, suggesting that all of these genes play a role in biphenyl/PCB
      degradation. The substrate preferences of etbA1A2/ebdA1A2- and bphA1A2-encoded
      dioxygenases for PCB congeners were examined using the corresponding mutants. The
      results indicated that these dioxygenase isozymes have different substrate
      preferences and that the etbA1A2/ebdA1A2-encoded isozyme is more active on highly
      chlorinated congeners than the bphA1A2-encoded one.

PMID- 16885290
TI  - Exposure to salt and organic acids increases the ability of Listeria
      monocytogenes to invade Caco-2 cells but decreases its ability to survive gastric
      stress.
AB  - The effects of environmental stress exposure on Listeria monocytogenes growth and
      virulence-associated characteristics were investigated. Specifically, we measured
      the effects of temperature (7 or 37 degrees C), pH (5.5 or 7.4), the presence of
      salt and organic acids (375 mM NaCl, 8.45 mM sodium diacetate [SD], 275 mM sodium
      lactate [SL], or a combination of NaCl, SD, and SL), and deletion of sigB, which
      encodes a key stress response regulator, on the ability of L. monocytogenes to
      grow, invade Caco-2 cells, and survive exposure to synthetic gastric fluid (pH
      2.5 or 4.5). Our results indicate that (i) L. monocytogenes log-phase generation
      times and maximum cell numbers are not dependent on the alternative sigma factor
      sigmaB in the presence of NaCl and organic acids at concentrations typically
      found in foods; (ii) growth inhibition of L. monocytogenes through the addition
      of organic acids is pH dependent; (iii) the ability of L. monocytogenes to invade
      Caco-2 cells is affected by growth phase, temperature, and the presence of salt
      and organic acids, with the highest relative invasion capabilities observed for
      cells grown with SL or NaCl at 37 degrees C and pH 7.4; (iv) growth of L.
      monocytogenes in the presence of NaCl, SD, or SL reduces its ability to survive
      exposure to gastric fluid; and (v) exposure of L. monocytogenes to gastric fluid
      reduces the enhanced invasiveness caused by growth in the presence of NaCl or SL.
      These findings suggest that virulence-associated characteristics that determine
      the L. monocytogenes infectious dose are likely to be affected by food-specific
      properties (e.g., pH or the presence of salt or organic acid).

PMID- 16885292
TI  - Characterization of the beta-ketoadipate pathway in Sinorhizobium meliloti.
AB  - Aromatic compounds represent an important source of energy for soil-dwelling
      organisms. The beta-ketoadipate pathway is a key metabolic pathway involved in
      the catabolism of the aromatic compounds protocatechuate and catechol, and here
      we show through enzymatic analysis and mutant analysis that genes required for
      growth and catabolism of protocatechuate in the soil-dwelling bacterium
      Sinorhizobium meliloti are organized on the pSymB megaplasmid in two
      transcriptional units designated pcaDCHGB and pcaIJF. The pcaD promoter was
      mapped by primer extension, and expression from this promoter is demonstrated to
      be regulated by the LysR-type protein PcaQ. Beta-ketoadipate succinyl-coenzyme A
      (CoA) transferase activity in S. meliloti was shown to be encoded by SMb20587 and
      SMb20588, and these genes have been renamed pcaI and pcaJ, respectively. These
      genes are organized in an operon with a putative beta-ketoadipyl-CoA thiolase
      gene (pcaF), and expression of the pcaIJF operon is shown to be regulated by an
      IclR-type transcriptional regulator, SMb20586, which we have named pcaR. We show
      that pcaR transcription is negatively autoregulated and that PcaR is a positive
      regulator of pcaIJF expression and is required for growth of S. meliloti on
      protocatechuate as the carbon source. The characterization of the protocatechuate
      catabolic pathway in S. meliloti offers an opportunity for comparison with
      related species, including Agrobacterium tumefaciens. Differences observed
      between S. meliloti and A. tumefaciens pcaIJ offer the first evidence of pca
      genes that may have been acquired after speciation in these closely related
      species.

PMID- 16885293
TI  - Ecological advantages of autolysis during the development and dispersal of
      Pseudoalteromonas tunicata biofilms.
AB  - In the ubiquitous marine bacterium Pseudoalteromonas tunicata, subpopulations of
      cells are killed by the production of an autocidal protein, AlpP, during biofilm
      development. Our data demonstrate an involvement of this process in two
      parameters, dispersal and phenotypic diversification, which are of importance for
      the ecology of this organism and for its survival within the environment. Cell
      death in P. tunicata wild-type biofilms led to a major reproducible dispersal
      event after 192 h of biofilm development. The dispersal was not observed with a
      DeltaAlpP mutant strain. Using flow cytometry and the fluorescent dye DiBAC4(3),
      we also show that P. tunicata wild-type cells that disperse from biofilms have
      enhanced metabolic activity compared to those cells that disperse from DeltaAlpP
      mutant biofilms, possibly due to nutrients released from dead cells. Furthermore,
      we report that there was considerable phenotypic variation among cells dispersing
      from wild-type biofilms but not from the DeltaAlpP mutant. Wild-type cells that
      dispersed from biofilms showed significantly increased variations in growth,
      motility, and biofilm formation, which may be important for successful
      colonization of new surfaces. These findings suggest for the first time that the
      autocidal events mediated by an antibacterial protein can confer ecological
      advantages to the species by generating a metabolically active and phenotypically
      diverse subpopulation of dispersal cells.

PMID- 16885294
TI  - Peptidoglycan from Bacillus cereus mediates commensalism with rhizosphere
      bacteria from the Cytophaga-Flavobacterium group.
AB  - Previous research in our laboratory revealed that the introduction of Bacillus
      cereus UW85 can increase the populations of bacteria from the Cytophaga
      Flavobacterium (CF) group of the Bacteroidetes phylum in the soybean rhizosphere,
      suggesting that these rhizosphere microorganisms have a beneficial relationship
      (G. S. Gilbert, J. L. Parke, M. K. Clayton, and J. Handelsman, Ecology 74:840
      854, 1993). In the present study, we determined the frequency at which CF
      bacteria coisolated with B. cereus strains from the soybean rhizosphere and the
      mechanism by which B. cereus stimulates the growth of CF rhizosphere strains in
      root exudate media. In three consecutive years of sampling, CF strains
      predominated among coisolates obtained with B. cereus isolates from field-grown
      soybean roots. In root exudate media, the presence of B. cereus was required for
      CF coisolate strains to reach high population density. However, rhizosphere
      isolates from the phylum Proteobacteria grew equally well in the presence and
      absence of B. cereus, and the presence of CF coisolates did not affect the growth
      of B. cereus. Peptidoglycan isolated from B. cereus cultures stimulated growth of
      the CF rhizosphere bacterium Flavobacterium johnsoniae, although culture
      supernatant from B. cereus grown in root exudate media did not. These results
      suggest B. cereus and CF rhizosphere bacteria have a commensal relationship in
      which peptidoglycan produced by B. cereus stimulates the growth of CF bacteria.

PMID- 16885295
TI  - Molecular fingerprinting of Cryptosporidium oocysts isolated during water
      monitoring.
AB  - We developed and validated a PCR-based method for identifying Cryptosporidium
      species and/or genotypes present on oocyst-positive microscope slides. The method
      involves removing coverslips and oocysts from previously examined slides followed
      by DNA extraction. We tested four loci, the 18S rRNA gene (N18SDIAG and
      N18SXIAO), the Cryptosporidium oocyst wall protein (COWP) gene (STN-COWP), and
      the dihydrofolate reductase (dhfr) gene (by multiplex allele-specific PCR), for
      amplifying DNA from low densities of Cryptosporidium parvum oocysts
      experimentally seeded onto microscope slides. The N18SDIAG locus performed
      consistently better than the other three tested. Purified oocysts from humans
      infected with C. felis, C. hominis, and C. parvum and commercially purchased C.
      muris were used to determine the sensitivities of three loci (N18SDIAG, STN-COWP,
      and N18SXIAO) to detect low oocyst densities. The N18SDIAG primers provided the
      greatest number of positive results, followed by the N18SXIAO primers and then
      the STN-COWP primers. Some oocyst-positive slides failed to generate a PCR
      product at any of the loci tested, but the limit of sensitivity is not entirely
      based on oocyst number. Sixteen of 33 environmental water monitoring
      Cryptosporidium slides tested (oocyst numbers ranging from 1 to 130) contained
      mixed Cryptosporidium species. The species/genotypes most commonly found were C.
      muris or C. andersoni, C. hominis or C. parvum, and C. meleagridis or
      Cryptosporidium sp. cervine, ferret, and mouse genotypes. Oocysts on one slide
      contained Cryptosporidium muskrat genotype II DNA.

PMID- 16885296
TI  - Impact of protists on the activity and structure of the bacterial community in a
      rice field soil.
AB  - Flooded rice fields have become a model system for the study of soil microbial
      ecology. In Italian rice fields, in particular, aspects from biogeochemistry to
      molecular ecology have been studied, but the impact of protistan grazing on the
      structure and function of the prokaryotic community has not been examined yet. We
      compared an untreated control soil with a gamma-radiation-sterilized soil that
      had been reinoculated with a natural bacterial assemblage. In order to verify
      that the observed effects were due to protistan grazing and did not result from
      sterilization, we set up a third set of microcosms containing sterilized soil
      that had been reinoculated with natural assemblage bacteria plus protists. The
      spatial and temporal changes in the protistan and prokaryotic communities were
      examined by denaturing gradient gel electrophoresis (DGGE) and terminal
      restriction fragment length polymorphism (T-RFLP) analysis, respectively, both
      based on the small-subunit gene. Sequences retrieved from DGGE bands were
      preferentially affiliated with Cercozoa and other bacteriovorous flagellates.
      Without protists, the level of total DNA increased with incubation time,
      indicating that the level of the microbial biomass was elevated.
      Betaproteobacteria were preferentially preyed upon, while low-G + C-content gram
      positive bacteria became more dominant under grazing pressure. The bacterial
      diversity detectable by T-RFLP analysis was greater in the presence of protists.
      The level of extractable NH4+ was lower and the level of extractable SO4(2-) was
      higher without protists, indicating that nitrogen mineralization and SO4(2-)
      reduction were stimulated by protists. Most of these effects were more obvious in
      the partially oxic surface layer (0 to 3 mm), but they could also be detected in
      the anoxic subsurface layer (10 to 13 mm). Our observations fit well into the
      overall framework developed for protistan grazing, but with some modifications
      pertinent to the wetland situation: O2 was a major control, and O2 availability
      may have limited directly and indirectly the development of protists. Although
      detectable in the lower anoxic layer, grazing effects were much more obvious in
      the partially oxic surface layer.

PMID- 16885297
TI  - Metabolic profiles and genetic diversity of denitrifying communities in activated
      sludge after addition of methanol or ethanol.
AB  - External carbon sources can enhance denitrification rates and thus improve
      nitrogen removal in wastewater treatment plants. The effects of adding methanol
      and ethanol on the genetic and metabolic diversity of denitrifying communities in
      activated sludge were compared using a pilot-scale plant with two parallel lines.
      A full-scale plant receiving the same municipal wastewater, but without external
      carbon source addition, was the reference. Metabolic profiles obtained from
      potential denitrification rates with 10 electron donors showed that the
      denitrifying communities altered their preferences for certain compounds after
      supplementation with methanol or ethanol and that methanol had the greater
      impact. Clone libraries of nirK and nirS genes, encoding the two different
      nitrite reductases in denitrifiers, revealed that methanol also increased the
      diversity of denitrifiers of the nirS type, which indicates that denitrifiers
      favored by methanol were on the rise in the community. This suggests that there
      might be a niche differentiation between nirS and nirK genotypes during activated
      sludge processes. The composition of nirS genotypes also varied greatly among all
      samples, whereas the nirK communities were more stable. The latter was confirmed
      by denaturing gradient gel electrophoresis of nirK communities on all sampling
      occasions. Our results support earlier hypotheses that the compositions of
      denitrifier communities change during predenitrification processes when external
      carbon sources are added, although no severe effect could be observed from an
      operational point of view.

PMID- 16885298
TI  - Targeting species-specific low-affinity 16S rRNA binding sites by using peptide
      nucleic acids for detection of Legionellae in biofilms.
AB  - Using fluorescence in situ hybridization to detect bacterial groups has several
      inherent limitations. DNA probes are generally used, targeting sites on the 16S
      rRNA. However, much of the 16S rRNA is highly conserved, with variable regions
      often located in inaccessible areas where secondary structures can restrict probe
      access. Here, we describe the use of peptide nucleic acid (PNA) probes as a
      superior alternative to DNA probes, especially when used for environmental
      samples. A complex bacterial genus (Legionella) was studied, and two probes were
      designed, one to detect all species and one targeted to Legionella pneumophila.
      These probes were developed from existing sequences and are targeted to low
      binding-affinity sites on the 16S rRNA. In total, 47 strains of Legionella were
      tested. In all cases, the Legionella spp. PNA probe labeled cells strongly but
      did not bind to any non-Legionella species. Likewise, the specific L. pneumophila
      PNA probe labeled only strains of L. pneumophila. By contrast, the equivalent DNA
      probes performed poorly. To assess the applicability of this method for use on
      environmental samples, drinking-water biofilms were spiked with a known
      concentration of L. pneumophila bacteria. Quantifications of the L. pneumophila
      bacteria were compared using PNA hybridization and standard culture methods. The
      culture method quantified only 10% of the number of L. pneumophila bacteria found
      by PNA hybridization. This illustrates the value of this method for use on
      complex environmental samples, especially where cells may be in a viable but
      noncultivable state.

PMID- 16885299
TI  - Comparative, collaborative, and on-site validation of a TaqMan PCR method as a
      tool for certified production of fresh, campylobacter-free chickens.
AB  - Certified Campylobacter-free poultry products have been produced in Denmark since
      2002, the first example of fresh (unprocessed and nonfrozen) chickens labeled
      "Campylobacter free." This success occurred partly through use of a 4-hour gel
      based PCR testing scheme on fecal swabs. In this study, a faster, real-time PCR
      approach was validated in comparative and collaborative trials, based on
      recommendations from the Nordic system for validation of alternative
      microbiological methods (NordVal). The comparative real-time PCR trial was
      performed in comparison to two reference culture protocols on naturally
      contaminated samples (99 shoe covers, 101 cloacal swabs, 102 neck skins from
      abattoirs, and 100 retail neck skins). Culturing included enrichment in both
      Bolton and Preston broths followed by isolation on Preston agar and mCCDA. In one
      or both culture protocols, 169 samples were identified as positive. The
      comparative trial resulted in relative accuracy, sensitivity, and specificity of
      98%, 95%, and 97%, respectively. The collaborative trial included nine
      laboratories testing neck skin, cloacal swab, and shoe cover samples, spiked with
      low, medium, and high concentrations of Campylobacter jejuni. Valid results were
      obtained from six of the participating laboratories. Accuracy for high levels was
      100% for neck skin and cloacal swab samples. For low levels, accuracy was 100%
      and 92% for neck skin and cloacal swab samples, respectively; however, detection
      in shoe cover samples failed. A second collaborative trial, with an optimized DNA
      extraction procedure, gave 100% accuracy results for all three spiking levels.
      Finally, on-site validation at the abattoir on a flock basis was performed on 400
      samples. Real-time PCR correctly identified 10 of 20 flocks as positive; thus,
      the method fulfilled the NordVal validation criteria and has since been
      implemented at a major abattoir.

PMID- 16885300
TI  - Identification of a gene cluster for biosynthesis of mannosylerythritol lipids in
      the basidiomycetous fungus Ustilago maydis.
AB  - Many microorganisms produce surface-active substances that enhance the
      availability of water-insoluble substrates. Although many of these biosurfactants
      have interesting potential applications, very little is known about their
      biosynthesis. The basidiomycetous fungus Ustilago maydis secretes large amounts
      of mannosylerythritol lipids (MELs) under conditions of nitrogen starvation. We
      recently described a putative glycosyltransferase, Emt1, which is essential for
      MEL biosynthesis and whose expression is strongly induced by nitrogen limitation.
      We used DNA microarray analysis to identify additional genes involved in MEL
      biosynthesis. Here we show that emt1 is part of a gene cluster which comprises
      five open reading frames. Three of the newly identified proteins, Mac1, Mac2, and
      Mat1, contain short sequence motifs characteristic for acyl- and
      acetyltransferases. Mutational analysis revealed that Mac1 and Mac2 are essential
      for MEL production, which suggests that they are involved in the acylation of
      mannosylerythritol. Deletion of mat1 resulted in the secretion of completely
      deacetylated MELs, as determined by mass spectrometry. We overexpressed Mat1 in
      Escherichia coli and demonstrated that this enzyme acts as an acetyl coenzyme A
      dependent acetyltransferase. Remarkably, Mat1 displays relaxed regioselectivity
      and is able to acetylate mannosylerythritol at both the C-4 and C-6 hydroxyl
      groups. Based on these results, we propose a biosynthesis pathway for the
      generation of mannosylerythritol lipids in U. maydis.

PMID- 16885301
TI  - Bacterioplankton community composition along a salinity gradient of sixteen high
      mountain lakes located on the Tibetan Plateau, China.
AB  - The influence of altitude and salinity on bacterioplankton community composition
      (BCC) in 16 high-mountain lakes located at altitudes of 2,817 to 5,134 m on the
      Eastern Qinghai-Xizang (Tibetan) Plateau, China, spanning a salinity gradient
      from 0.02% (freshwater) to 22.3% (hypersaline), was investigated. Three different
      methods, fluorescent in situ hybridization, denaturing gradient gel
      electrophoresis (DGGE) with subsequent band sequencing, and reverse line blot
      hybridization (RLB) with probes targeting 17 freshwater bacterial groups, were
      used for analysis of BCC. Furthermore, the salt tolerances of 47 strains
      affiliated with groups detected in or isolated from the Tibetan habitats were
      investigated. Altitude was not found to influence BCC significantly within the
      investigated range. Several groups of typical freshwater bacteria, e.g., the ACK
      M1 cluster and the Polynucleobacter group, were detected in habitats located
      above 4,400 m. Salinity was found to be the dominating environmental factor
      controlling BCC in the investigated lakes, resulting in only small overlaps in
      the BCCs of freshwater and hypersaline lakes. The relative abundances of
      different classes of Proteobacteria showed a sharp succession along the salinity
      gradient. Both DGGE and RLB demonstrated that a few freshwater bacterial groups,
      e.g., GKS98 and LD2, appeared over wide salinity ranges. Six freshwater isolates
      affiliated with the GKS98 cluster grew in ecophysiological experiments at maximum
      salinities of 0.3% to 0.7% (oligosaline), while this group was detected in
      habitats with salinities up to 6.7% (hypersaline). This observation indicated
      ecologically significant differences in ecophysiological adaptations among
      members of this narrow phylogenetic group and suggested ecological significance
      of microdiversity.

PMID- 16885302
TI  - Temporal expression of respiratory genes in an enrichment culture containing
      Dehalococcoides ethenogenes.
AB  - Multiple reductive dehalogenase (RDase), hydrogenase (H2ase), and other
      respiration-associated (RA) oxidoreductase genes have been identified in cultured
      representatives of Dehalococcoides. Although their products are likely to play
      key roles in the environmentally important process of reductive dechlorination,
      very little information is available about their regulation and specific
      functions. Here we show increased expression and temporal variability in the
      expression of five RDase genes and in the expression of genes for a putative
      formate dehydrogenase (Fdh) and two H2ases, including a periplasmic [Ni/Fe] H2ase
      (Hup) and a cytoplasmic [Fe] H2ase (Vhu). mRNA transcripts extracted from
      tetrachloroethene-dechlorinating mixed cultures corresponding to Fdh, the H2ase
      Hup, and the RDase targets TceA and DET0162 were expressed most highly, with
      average levels 34 (+/- 7.5)-, 23 (+/- 6.7)-, 16 (+/- 3.3)-, and 13 (+/- 3.3)-fold
      higher, respectively, than that for RNA polymerase (RpoB). H2ase and RA
      transcripts reached their respective expression maxima within the first 2 h after
      feeding. RDase transcripts, however, were most highly expressed after 3 h and
      exhibited greater temporal variability than other transcripts. Comparison with D.
      ethenogenes strain 195 pure culture expression levels indicated that RDase
      DET1545 was more highly expressed in mixed cultures, where, on average, its
      transcript level was sixfold higher than that of RpoB. While the specific
      functions of several of these gene products remain elusive, the high expression
      levels and temporal variability reported here suggest that these groups of
      enzymes are metabolically important for the respiration of chlorinated ethenes in
      mixed cultures containing Dehalococcoides.

PMID- 16885303
TI  - Improvement of lactic acid production in Saccharomyces cerevisiae by cell sorting
      for high intracellular pH.
AB  - Yeast strains expressing heterologous L-lactate dehydrogenases can produce lactic
      acid. Although these microorganisms are tolerant of acidic environments, it is
      known that at low pH, lactic acid exerts a high level of stress on the cells. In
      the present study we analyzed intracellular pH (pHi) and viability by staining
      with cSNARF-4F and ethidium bromide, respectively, of two lactic-acid-producing
      strains of Saccharomyces cerevisiae, CEN.PK m850 and CEN.PK RWB876. The results
      showed that the strain producing more lactic acid, CEN.PK m850, has a higher pHi.
      During batch culture, we observed in both strains a reduction of the mean pHi and
      the appearance of a subpopulation of cells with low pHi. Simultaneous analysis of
      pHi and viability proved that the cells with low pHi were dead. Based on the
      observation that the better lactic-acid-producing strain had a higher pHi and
      that the cells with low pHi were dead, we hypothesized that we might find better
      lactic acid producers by screening for cells within the highest pHi range. The
      screening was performed on UV-mutagenized populations through three consecutive
      rounds of cell sorting in which only the viable cells within the highest pHi
      range were selected. The results showed that lactic acid production was
      significantly improved in the majority of the mutants obtained compared to the
      parental strains. The best lactic-acid-producing strain was identified within the
      screening of CEN.PK m850 mutants.

PMID- 16885304
TI  - Identification and preliminary characterization of two cDNAs encoding unique
      carbonic anhydrases from the marine alga Emiliania huxleyi.
AB  - Marine coccolithophorid algae are thought to play a significant role in carbon
      cycling due to their ability to incorporate dissolved inorganic carbon (DIC) into
      both calcite and photosynthetic products. Among coccolithophorids, Emiliania
      huxleyi is the most prolific, forming massive blooms that affect the global
      environment. In addition to its ecological importance, the elaborate calcite
      structures (coccoliths) are being investigated for the design of potential
      materials for science and biotechnological devices. To date, most of the research
      focus in this organism has involved the partitioning of DIC between calcification
      and photosynthesis, primarily using measurements of an external versus internal
      carbonic anhydrase (CA) activity under defined conditions. The actual genes,
      proteins, and pathways employed in these processes have not been identified and
      characterized (see the work of Quinn et al. in this issue [P. Quinn, R. M.
      Bowers, X. Zhang, T. M. Wahlund, M. A. Fanelli, D. Olszova, and B. A. Read, Appl.
      Environ. Microbiol. 72:5512-5526, 2006]). In this study, the cloning and
      preliminary characterization of two genetically distinct carbonic anhydrase cDNAs
      are described. Phylogenetic analysis indicated that these two genes belonged to
      the gamma (gamma-EhCA2) and delta (delta-EhCA1) classes of carbonic anhydrases.
      The deduced amino acid sequence of delta-EhCA1 revealed that it encodes a protein
      of 702 amino acids (aa) (ca. 77.3 kDa), with a transmembrane N-terminal region of
      373 aa and an in-frame C-terminal open reading frame of 329 aa that defines the
      CA region. The gamma-EhCA2 protein was 235 aa in length (ca. 24.9 kDa) and was
      successfully expressed in Escherichia coli BL21(DE3) and purified as an active
      recombinant CA. The expression levels of each transcript from quantitative
      reverse transcription-PCR experiments under bicarbonate limitation and over a 24
      h time course suggest that these isozymes perform different functions in E.
      huxleyi.

PMID- 16885306
TI  - Phylogeny of 16S rRNA, ribulose 1,5-bisphosphate carboxylase/oxygenase, and
      adenosine 5'-phosphosulfate reductase genes from gamma- and alphaproteobacterial
      symbionts in gutless marine worms (oligochaeta) from Bermuda and the Bahamas.
AB  - Gutless oligochaetes are small marine worms that live in obligate associations
      with bacterial endosymbionts. While symbionts from several host species belonging
      to the genus Olavius have been described, little is known of the symbionts from
      the host genus Inanidrilus. In this study, the diversity of bacterial
      endosymbionts in Inanidrilus leukodermatus from Bermuda and Inanidrilus
      makropetalos from the Bahamas was investigated using comparative sequence
      analysis of the 16S rRNA gene and fluorescence in situ hybridization. As in all
      other gutless oligochaetes examined to date, I. leukodermatus and I. makropetalos
      harbor large, oval bacteria identified as Gamma 1 symbionts. The presence of
      genes coding for ribulose-1,5-bisphosphate carboxylase/oxygenase form I (cbbL)
      and adenosine 5'-phosphosulfate reductase (aprA) supports earlier studies
      indicating that these symbionts are chemoautotrophic sulfur oxidizers.
      Alphaproteobacteria, previously identified only in the gutless oligochaete
      Olavius loisae from the southwest Pacific Ocean, coexist with the Gamma 1
      symbionts in both I. leukodermatus and I. makropetalos, with the former harboring
      four and the latter two alphaproteobacterial phylotypes. The presence of these
      symbionts in hosts from such geographically distant oceans as the Atlantic and
      Pacific suggests that symbioses with alphaproteobacterial symbionts may be
      widespread in gutless oligochaetes. The high phylogenetic diversity of bacterial
      endosymbionts in two species of the genus Inanidrilus, previously known only from
      members of the genus Olavius, shows that the stable coexistence of multiple
      symbionts is a common feature in gutless oligochaetes.

PMID- 16885307
TI  - Basin-wide analysis of the dynamics of fecal contamination and fecal source
      identification in Tillamook Bay, Oregon.
AB  - The objectives of this study were to elucidate spatial and temporal dynamics in
      source-specific Bacteroidales 16S rRNA genetic marker data across a watershed; to
      compare these dynamics to fecal indicator counts, general measurements of water
      quality, and climatic forces; and to identify geographic areas of intense
      exposure to specific sources of contamination. Samples were collected during a 2
      year period in the Tillamook basin in Oregon at 30 sites along five river
      tributaries and in Tillamook Bay. We performed Bacteroidales PCR assays with
      general, ruminant-source-specific, and human-source-specific primers to identify
      fecal sources. We determined the Escherichia coli most probable number,
      temperature, turbidity, and 5-day precipitation. Climate and water quality data
      collectively supported a rainfall runoff pattern for microbial source input that
      mirrored the annual precipitation cycle. Fecal sources were statistically linked
      more closely to ruminants than to humans; there was a 40% greater probability of
      detecting a ruminant source marker than a human source marker across the basin.
      On a sample site basis, the addition of fecal source tracking data provided new
      information linking elevated fecal indicator bacterial loads to specific point
      and nonpoint sources of fecal pollution in the basin. Inconsistencies in E. coli
      and host-specific marker trends suggested that the factors that control the
      quantity of fecal indicators in the water column are different than the factors
      that influence the presence of Bacteroidales markers at specific times of the
      year. This may be important if fecal indicator counts are used as a criterion for
      source loading potential in receiving waters.

PMID- 16885305
TI  - cDNA microarrays as a tool for identification of biomineralization proteins in
      the coccolithophorid Emiliania huxleyi (Haptophyta).
AB  - Marine unicellular coccolithophore algae produce species-specific calcite scales
      otherwise known as coccoliths. While the coccoliths and their elaborate
      architecture have attracted the attention of investigators from various
      scientific disciplines, our knowledge of the underpinnings of the process of
      biomineralization in this alga is still in its infancy. The processes of
      calcification and coccolithogenesis are highly regulated and likely to be
      complex, requiring coordinated expression of many genes and pathways. In this
      study, we have employed cDNA microarrays to investigate changes in gene
      expression associated with biomineralization in the most abundant
      coccolithophorid, Emiliania huxleyi. Expression profiling of cultures grown under
      calcifying and noncalcifying conditions has been carried out using cDNA
      microarrays corresponding to approximately 2,300 expressed sequence tags. A total
      of 127 significantly up- or down-regulated transcripts were identified using a P
      value of 0.01 and a change of >2.0-fold. Real-time reverse transcriptase PCR was
      used to test the overall validity of the microarray data, as well as the
      relevance of many of the proteins predicted to be associated with
      biomineralization, including a novel gamma-class carbonic anhydrase (A. R. Soto,
      H. Zheng, D. Shoemaker, J. Rodriguez, B. A. Read, and T. M. Wahlund, Appl.
      Environ. Microbiol. 72:5500-5511, 2006). Differentially regulated genes include
      those related to cellular metabolism, ion channels, transport proteins, vesicular
      trafficking, and cell signaling. The putative function of the vast majority of
      candidate transcripts could not be defined. Nonetheless, the data described
      herein represent profiles of the transcription changes associated with
      biomineralization-related pathways in E. huxleyi and have identified novel and
      potentially useful targets for more detailed analysis.

PMID- 16885308
TI  - Microbial colonization and competition on the marine alga Ulva australis.
AB  - Pseudalteromonas tunicata and Roseobacter gallaeciensis are biofilm-forming
      marine bacteria that are often found in association with the surface of the green
      alga Ulva australis. They are thought to benefit the plant host by producing
      inhibitory compounds that are active against common fouling organisms. We
      investigated factors that influence the ability of P. tunicata and R.
      gallaeciensis to attach to and colonize the plant surface and also the
      competitive interactions that occur between these organisms and other isolates
      from U. australis during biofilm formation on the plant surface. A surprisingly
      high number of P. tunicata cells, at least 10(8) cells ml(-1), were required for
      colonization and establishment of a population of cells that persists on axenic
      surfaces of U. australis. Factors that enhanced colonization of P. tunicata
      included inoculation in the dark and pregrowth of inocula in medium containing
      cellobiose as the sole carbon source (cellulose is a major surface polymer of U.
      australis). It was also found that P. tunicata requires the presence of a mixed
      microbial community to colonize effectively. In contrast, R. gallaeciensis
      effectively colonized the plant surface under all conditions tested. Studies of
      competitive interactions on the plant surface revealed that P. tunicata was
      numerically dominant compared with all other bacterial isolates tested (except R.
      gallaeciensis), and this dominance was linked to production of the antibacterial
      protein AlpP. Generally, P. tunicata was able to coexist with competing strains,
      and each strain existed as microcolonies in spatially segregated regions of the
      plant. R. gallaeciensis was numerically dominant compared with all strains tested
      and was able to invade and disperse preestablished biofilms. This study
      highlighted the fact that microbial colonization of U. australis surfaces is a
      dynamic process and demonstrated the differences in colonization strategies
      exhibited by the epiphytic bacteria P. tunicata and R. gallaeciensis.

PMID- 16885309
TI  - Discovery of a marine bacterium producing 4-hydroxybenzoate and its alkyl esters,
      parabens.
AB  - Chemically synthesized 4-hydroxybenzoate (4HBA) is widely used in the chemical
      and electrical industries as a material for producing polymers such as those of
      the liquid crystal type. Its alkyl esters, called parabens, have been the most
      widely used preservatives by the food and cosmetic industries. We report here for
      the first time a microorganism, a marine bacterium, which biosynthesizes these
      petrochemical products. The marine bacterial strain, A4B-17, which was found to
      belong to the genus Microbulbifer on the basis of its rRNA and gyrB sequences,
      was isolated from an ascidian in the coastal waters of Palau. Strain A4B-17 was,
      surprisingly, found to produce 10 mg/liter of 4HBA, together with its butyl (24
      mg/liter), heptyl (0.4 mg/liter), and nonyl (6 mg/liter) esters. We therefore
      characterized 23 other marine bacteria belonging to the genus Microbulbifer,
      which our institute had previously isolated from various marine environments, and
      found that these bacteria also produced 4HBA, although with low production levels
      (less than one-fifth of that produced by A4B-17). We also show that the alkyl
      esters of 4HBA produced by strain A4B-17 were effective in preventing the growth
      of yeasts, molds, and gram-positive bacteria.

PMID- 16885310
TI  - Isolation, characterization, and ecology of cold-active, chemolithotrophic,
      sulfur-oxidizing bacteria from perennially ice-covered Lake Fryxell, Antarctica.
AB  - Novel strains of obligately chemolithoautotrophic, sulfur-oxidizing bacteria have
      been isolated from various depths of Lake Fryxell, Antarctica. Physiological,
      morphological, and phylogenetic analyses showed these strains to be related to
      mesophilic Thiobacillus species, such as T. thioparus. However, the
      psychrotolerant Antarctic isolates showed an adaptation to cold temperatures and
      thus should be active in the nearly freezing waters of the lake. Enumeration by
      most-probable-number analysis in an oxic, thiosulfate-containing medium revealed
      that the sulfur-oxidizing chemolithotroph population peaks precisely at the
      oxycline (9.5 m), although viable cells exist well into the anoxic, sulfidic
      waters of the lake. The sulfur-oxidizing bacteria described here likely play a
      key role in the biogeochemical cycling of carbon and sulfur in Lake Fryxell.

PMID- 16885311
TI  - Isolation and identification of Rickettsia massiliae from Rhipicephalus
      sanguineus ticks collected in Arizona.
AB  - Twenty Rhipicephalus sanguineus ticks collected in eastern Arizona were tested by
      PCR assay to establish their infection rate with spotted fever group rickettsiae.
      With a nested PCR assay which detects a fragment of the Rickettsia genus-specific
      17-kDa antigen gene (htrA), five ticks (25%) were found to contain rickettsial
      DNA. One rickettsial isolate was obtained from these ticks by inoculating a
      suspension of a triturated tick into monolayers of Vero E6 monkey kidney cells
      and XTC-2 clawed toad cells, and its cell culture and genotypic characteristics
      were determined. Fragments of the 16S rRNA, GltA, rOmpA, rOmpB, and Sca4 genes
      had 100%, 100%, 99%, 99%, and 99%, respectively, nucleotide similarity to
      Rickettsia massiliae strain Bar29, previously isolated from R. sanguineus in
      Catalonia, Spain (L. Beati et al., J. Clin. Microbiol. 34:2688-2694, 1996). The
      new isolate, AZT80, does not elicit cytotoxic effects in Vero cells and causes a
      persistent infection in XTC-2 cells. The AZT80 strain is susceptible to
      doxycycline but resistant to rifampin and erythromycin. Whether R. massiliae
      AZT80 is pathogenic or infectious for dogs and humans or can cause seroconversion
      to spotted fever group antigens in the United States is unknown.

PMID- 16885312
TI  - Temporal transcriptomic analysis as Desulfovibrio vulgaris Hildenborough
      transitions into stationary phase during electron donor depletion.
AB  - Desulfovibrio vulgaris was cultivated in a defined medium, and biomass was
      sampled for approximately 70 h to characterize the shifts in gene expression as
      cells transitioned from the exponential to the stationary phase during electron
      donor depletion. In addition to temporal transcriptomics, total protein,
      carbohydrate, lactate, acetate, and sulfate levels were measured. The microarray
      data were examined for statistically significant expression changes, hierarchical
      cluster analysis, and promoter element prediction and were validated by
      quantitative PCR. As the cells transitioned from the exponential phase to the
      stationary phase, a majority of the down-expressed genes were involved in
      translation and transcription, and this trend continued at the remaining times.
      There were general increases in relative expression for intracellular trafficking
      and secretion, ion transport, and coenzyme metabolism as the cells entered the
      stationary phase. As expected, the DNA replication machinery was down-expressed,
      and the expression of genes involved in DNA repair increased during the
      stationary phase. Genes involved in amino acid acquisition, carbohydrate
      metabolism, energy production, and cell envelope biogenesis did not exhibit
      uniform transcriptional responses. Interestingly, most phage-related genes were
      up-expressed at the onset of the stationary phase. This result suggested that
      nutrient depletion may affect community dynamics and DNA transfer mechanisms of
      sulfate-reducing bacteria via the phage cycle. The putative feoAB system (in
      addition to other presumptive iron metabolism genes) was significantly up
      expressed, and this suggested the possible importance of Fe2+ acquisition under
      metal-reducing conditions. The expression of a large subset of carbohydrate
      related genes was altered, and the total cellular carbohydrate levels declined
      during the growth phase transition. Interestingly, the D. vulgaris genome does
      not contain a putative rpoS gene, a common attribute of the delta-Proteobacteria
      genomes sequenced to date, and the transcription profiles of other putative rpo
      genes were not significantly altered. Our results indicated that in addition to
      expected changes (e.g., energy conversion, protein turnover, translation,
      transcription, and DNA replication and repair), genes related to phage, stress
      response, carbohydrate flux, the outer envelope, and iron homeostasis played
      important roles as D. vulgaris cells experienced electron donor depletion.

PMID- 16885314
TI  - Dominant microbial populations in limestone-corroding stream biofilms, Frasassi
      cave system, Italy.
AB  - Waters from an extensive sulfide-rich aquifer emerge in the Frasassi cave system,
      where they mix with oxygen-rich percolating water and cave air over a large
      surface area. The actively forming cave complex hosts a microbial community,
      including conspicuous white biofilms coating surfaces in cave streams, that is
      isolated from surface sources of C and N. Two distinct biofilm morphologies were
      observed in the streams over a 4-year period. Bacterial 16S rDNA libraries were
      constructed from samples of each biofilm type collected from Grotta Sulfurea in
      2002. beta-, gamma-, delta-, and epsilon-proteobacteria in sulfur-cycling clades
      accounted for > or = 75% of clones in both biofilms. Sulfate-reducing and sulfur
      disproportionating delta-proteobacterial sequences in the clone libraries were
      abundant and diverse (34% of phylotypes). Biofilm samples of both types were
      later collected at the same location and at an additional sample site in Ramo
      Sulfureo and examined, using fluorescence in situ hybridization (FISH). The
      biomass of all six stream biofilms was dominated by filamentous gamma
      proteobacteria with Beggiatoa-like and/or Thiothrix-like cells containing
      abundant sulfur inclusions. The biomass of epsilon-proteobacteria detected using
      FISH was consistently small, ranging from 0 to less than 15% of the total
      biomass. Our results suggest that S cycling within the stream biofilms is an
      important feature of the cave biogeochemistry. Such cycling represents positive
      biological feedback to sulfuric acid speleogenesis and related processes that
      create subsurface porosity in carbonate rocks.

PMID- 16885313
TI  - Rickettsia felis from cat fleas: isolation and culture in a tick-derived cell
      line.
AB  - Rickettsia felis, the etiologic agent of spotted fever, is maintained in cat
      fleas by vertical transmission and resembles other tick-borne spotted fever group
      rickettsiae. In the present study, we utilized an Ixodes scapularis-derived tick
      cell line, ISE6, to achieve isolation and propagation of R. felis. A cytopathic
      effect of increased vacuolization was commonly observed in R. felis-infected
      cells, while lysis of host cells was not evident despite large numbers of
      rickettsiae. Electron microscopy identified rickettsia-like organisms in ISE6
      cells, and sequence analyses of portions of the citrate synthase (gltA), 16S
      rRNA, Rickettsia genus-specific 17-kDa antigen, and spotted fever group-specific
      outer membrane protein A (ompA) genes and, notably, R. felis conjugative plasmids
      indicate that this cultivatable strain (LSU) was R. felis. Establishment of R.
      felis (LSU) in a tick-derived cell line provides an alternative and promising
      system for the expansion of studies investigating the interactions between R.
      felis and arthropod hosts.

PMID- 16885315
TI  - Quantitative PCR method for sensitive detection of ruminant fecal pollution in
      freshwater and evaluation of this method in alpine karstic regions.
AB  - A quantitative TaqMan minor-groove binder real-time PCR assay was developed for
      the sensitive detection of a ruminant-specific genetic marker in fecal members of
      the phylum Bacteroidetes. The qualitative and quantitative detection limits
      determined were 6 and 20 marker copies per PCR, respectively. Tested ruminant
      feces contained an average of 4.1 x 10(9) marker equivalents per g, allowing the
      detection of 1.7 ng of feces per filter in fecal suspensions. The marker was
      detected in water samples from a karstic catchment area at levels matching a
      gradient from negligible to considerable ruminant fecal influence (from not
      detectable to 10(5) marker equivalents per liter).

PMID- 16885316
TI  - Survival of Lactobacillus casei in the human digestive tract after consumption of
      fermented milk.
AB  - A human trial was carried out to assess the ileal and fecal survival of
      Lactobacillus casei DN-114 001 ingested in fermented milk. Survival rates were up
      to 51.2% in the ileum and 28.4% in the feces. The probiotic bacterium has the
      capacity to survive during its transit through the human gut.

PMID- 16885317
TI  - Direct molecular approach to monitoring bacterial colonization on vacuum-packaged
      beef.
AB  - Denaturing gradient gel electrophoresis allowed us to monitor total bacterial
      communities and to establish a pattern of succession between species in vacuum
      packaged beef stored at 2 and 8 degrees C for 9 weeks and 14 days. Species
      specific PCR was used to confirm the presence of Lactobacillus sakei and
      Lactobacillus curvatus. Multiplex PCRs using 16S rRNA-specific primers allowed
      differentiation between Leuconostoc species. These methods provided the desired
      information about microbial diversity by detecting the main microorganisms
      capable of colonizing this ecological niche.

PMID- 16885318
TI  - The lactic acid-induced acid tolerance response in Salmonella enterica serovar
      Typhimurium induces sensitivity to hydrogen peroxide.
AB  - Transcriptome analyses of Salmonella enterica serovar Typhimurium revealed that
      15 genes were significantly up-regulated after 2 h of adaptation with lactic
      acid. cadB was the most highly up-regulated gene and was shown to be an essential
      component. Lactic acid-adapted cells exhibited sensitivity to hydrogen peroxide,
      likely due to down-regulation of the OxyR regulon.

PMID- 16885319
TI  - Development of a dinoflagellate-oriented PCR primer set leads to detection of
      picoplanktonic dinoflagellates from Long Island Sound.
AB  - We developed dinoflagellate-specific 18S rRNA gene primers. PCR amplification
      using these oligonucleotides for a picoplanktonic DNA sample from Long Island
      Sound yielded 24 clones, and all but one of these clones were dinoflagellates
      primarily belonging to undescribed and Amoebophrya-like lineages. These results
      highlight the need for a systematic investigation of picodinoflagellate diversity
      in both coastal and oceanic ecosystems.

PMID- 16885320
TI  - Diversity of Bacillus anthracis strains in Georgia and of vaccine strains from
      the former Soviet Union.
AB  - Despite the increased number of anthrax outbreaks in Georgia and the other
      Caucasian republics of the former Soviet Union, no data are available on the
      diversity of the Bacillus anthracis strains involved. There is also little data
      available on strains from the former Soviet Union, including the strains
      previously used for vaccine preparation. In this study we used eight-locus
      variable-number tandem repeat analyses to genotype 18 strains isolated from
      infected animals and humans at different sites across Georgia, where anthrax
      outbreaks have occurred in the last 10 years, and 5 strains widely used for
      preparation of human and veterinary vaccines in the former Soviet Union. Three
      different genotypes affiliated with the A3.a cluster were detected for the
      Georgian isolates. Two genotypes were previously shown to include Turkish
      isolates, indicating that there is a regional strain pattern in the South
      Caucasian-Turkish region. Four of the vaccine strains were polymorphic,
      exhibiting three different patterns of the cluster A1.a genotype and the cluster
      A3.b genotype. The genotype of vaccine strain 71/12, which is considered an
      attenuated strain in spite of the presence of both of the virulence pXO plasmids,
      appeared to be a novel genotype in the A1.a cluster.

PMID- 16885321
TI  - Random insertion of a TetR-inducing peptide tag into Escherichia coli proteins
      allows analysis of protein levels by induction of reporter gene expression.
AB  - The insertion element InsTipalpha was constructed to generate protein expression
      data. It randomly fuses the TetR-inducing peptide Tip to the affected reading
      frame. Fusion protein expression is quantified by Tet-regulated reporter gene
      expression. The expression patterns of tagged Escherichia coli genes fully agree
      with published data from transcriptional fusions or microarrays, validating the
      Tip tag approach.

PMID- 16885323
TI  - Carbon isotope fractionation during acetoclastic methanogenesis by Methanosaeta
      concilii in culture and a lake sediment.
AB  - The isotope enrichment factors (epsilon) in Methanosaeta concilii and in a lake
      sediment, where acetate was consumed only by Methanosaeta spp., were clearly less
      negative than the epsilon usually observed for Methanosarcina spp. The fraction
      of methane produced from acetate in the sediment, as determined by using stable
      isotope signatures, was 10 to 15% lower when the appropriate epsilon of
      Methanosaeta spp. was used.

PMID- 16885322
TI  - Occurrence of ammonia-oxidizing archaea in wastewater treatment plant
      bioreactors.
AB  - We report molecular evidence that ammonia-oxidizing archaea (AOA) occur in
      activated sludge bioreactors used to remove ammonia from wastewater. Using PCR
      primers targeting archaeal ammonia monooxygenase subunit A (amoA) genes, we
      retrieved and compared 75 sequences from five wastewater treatment plants
      operating with low dissolved oxygen levels and long retention times. All of these
      sequences showed similarity to sequences previously found in soil and sediments,
      and they were distributed primarily in four major phylogenetic clusters. One of
      these clusters contained virtually identical amoA sequences obtained from all
      five activated sludge samples (from Oregon, Wisconsin, Pennsylvania, and New
      Jersey) and accounted for 67% of all the sequences, suggesting that this AOA
      phylotype may be widespread in nitrifying bioreactors.

PMID- 16885324
TI  - A Mutation in the luxS gene influences Listeria monocytogenes biofilm formation.
AB  - Using a Vibrio harveyi reporter strain, we demonstrated that Listeria
      monocytogenes secretes a functional autoinducer 2 (AI-2)-like signal. A luxS
      deficient mutant produced a denser biofilm and attached to a glass surface 19
      fold better than the parent strain. Exogenous AI-2 failed to restore the wild
      type phenotype to the mutant. It seems that an intact luxS gene is associated
      with repression of components required for attachment and biofilm formation.

PMID- 16885325
TI  - Molecular biological detection of anaerobic gut fungi (Neocallimastigales) from
      landfill sites.
AB  - Oligonucleotide primers were designed for the 18S rRNA genes of members of the
      Neocallimastigales and used in a nested PCR protocol to amplify 787-bp fragments
      of DNA from landfill site samples. The specificities of the primers were
      confirmed by phylogenetic analysis of the environmental clone sequences, and this
      method can therefore now be used to investigate the ecology of the obligately
      anaerobic fungi. To our knowledge, this is the first demonstration of the
      occurrence of members of the Neocallimastigales outside the mammalian gut, and
      their distribution across the landfill samples examined here suggests that they
      are actively involved in cellulose degradation.

PMID- 16885326
TI  - Metal accumulation without enhanced oxalate secretion in wood degraded by brown
      rot fungi.
AB  - Brown rot fungi were incubated in agar and agar-wood microcosms containing
      metallic or hydroxide forms of Al, Cu, and Fe. Metal dissolution was associated
      with elevated oxalate concentrations in agar, but metals translocated into wood
      did not affect oxalate accumulation, crystal production, or decay rate,
      demonstrating a substrate-dependent oxalate dynamic.

PMID- 16885327
TI  - Molecular epidemiologic investigation of Campylobacter coli in swine production
      systems, using multilocus sequence typing.
AB  - Multilocus sequence typing of 151 Campylobacter coli isolates from swine reared
      in conventional (n = 74) and antimicrobial-free (n = 77) production systems
      revealed high genotypic diversity. Sequence type (ST) 1413 was predominant and
      observed among ciprofloxacin-resistant strains. We identified a C. coli ST 828
      clonal complex consisting of isolates from both production systems.

PMID- 16885328
TI  - Production of resveratrol in recombinant microorganisms.
AB  - Resveratrol production in Saccharomyces cerevisiae was compared to that in
      Escherichia coli. In both systems, 4-coumarate:coenzyme A ligase from tobacco and
      stilbene synthase from grapes were expressed. When p-coumaric acid was used as
      the precursor, resveratrol accumulations in the culture medium were observed to
      be comparable in E. coli (16 mg/liter) and yeast (6 mg/liter).

PMID- 16885329
TI  - Cloning and expression of two crystal protein genes, cry30Ba1 and cry44Aa1,
      obtained from a highly mosquitocidal strain, Bacillus thuringiensis subsp.
      entomocidus INA288.
AB  - Two novel crystal protein genes, cry30Ba and cry44Aa, were cloned from Bacillus
      thuringiensis subsp. entomocidus INA288 and expressed in an acrystalliferous
      strain. Cry44Aa crystals were highly toxic to second-instar Culex pipiens pallens
      (50% mortality concentration [LC50] = 6 ng/ml) and Aedes aegypti (LC50 = 12
      ng/ml); however, Cry30Ba crystals were not toxic.

PMID- 16885330
TI  - A cascade of modules of a network defines cancer progression.
AB  - Similar histologic subtypes of cancers often exhibit different spectrum of
      genetic and epigenetic alterations. The heterogeneity observed due to lack of
      consistent and defined alterations affecting a unique set of gene(s) or gene
      products in cancers derived from a specific tissue, or an organ, pose a challenge
      in unraveling the molecular basis of the disease. This dilemma also complicates
      diagnosis, prognosis, effective management, and treatment modalities. To
      streamline the available and emerging data into a coherent scheme of events, a
      multimodular molecular network (MMMN) cancer progression model is presented as a
      roadmap to dissect the complexity inherent to this disease. The fact that
      disruption/dysregulation of more than one alternate target gene could affect the
      functionality of each specific module of a cascade provides a molecular basis for
      genetic and epigenetic heterogeneity in any given cancer. Polymorphisms/mutations
      as well as the extracellular matrix and or the epigenetically/genetically
      conditioned surrounding stromal cells could also influence the rate of
      tumorigenesis and the properties of the tumor cells. The formulation of MMMN
      cancer progression models for specific cancers is likely to provide the
      blueprints for the markers and targets to aid diagnosis, prevention, and therapy
      of this deadly disease.

PMID- 16885331
TI  - Mitochondrial DNA mutations and apoptosis in mammalian aging.
AB  - Mutations in mitochondrial DNA (mtDNA) accumulate during aging, but their
      significance to longevity and age-associated disease has been uncertain.
      Recently, in support of the hypothesis that mtDNA integrity is important, we have
      shown that age-associated diseases arise more rapidly in mice where mtDNA
      mutations and increased levels of apoptosis occur at higher rates than normal due
      to expression of an error-prone mtDNA polymerase. Further studies in this model
      may provide deeper insights into the relationship between mitochondria, aging,
      and susceptibility to age-associated diseases, such as cancer.

PMID- 16885332
TI  - MicroRNA-cancer connection: the beginning of a new tale.
AB  - Cancer initiation and progression can involve microRNAs (miRNA), which are small
      noncoding RNAs that can regulate gene expression. Their expression profiles can
      be used for the classification, diagnosis, and prognosis of human malignancies.
      Loss or amplification of miRNA genes has been reported in a variety of cancers,
      and altered patterns of miRNA expression may affect cell cycle and survival
      programs. Germ-line and somatic mutations in miRNAs or polymorphisms in the mRNAs
      targeted by miRNAs may also contribute to cancer predisposition and progression.
      We propose that alterations in miRNA genes play a critical role in the
      pathophysiology of many, perhaps all, human cancers.

PMID- 16885333
TI  - Innate immune inflammatory response against enteric bacteria Helicobacter
      hepaticus induces mammary adenocarcinoma in mice.
AB  - Inflammation associated with bacterial infections is a risk factor for cancers in
      humans, yet its role in breast cancer remains poorly understood. We have
      previously shown that innate immune inflammatory response against intestinal
      bacteria is sufficient to induce colon cancer. Here we report that infecting Rag2
      deficient C57BL/6 Apc(Min/+) mice with an intestinal bacterial pathogen,
      Helicobacter hepaticus, significantly promotes mammary carcinoma in females and
      enhances intestinal adenoma multiplicity by a tumor necrosis factor alpha
      (TNFalpha)-dependent mechanism. The mammary and intestinal tumor development as
      well as the increase in proinflammatory mediators is suppressed by adoptive
      transfer of interleukin 10-competent CD4+CD45RB(lo)CD25+ regulatory (T(R)) cells.
      Furthermore, prior exposure of donor mice to H. hepaticus significantly enhances
      antitumor potency of their T(R) cells. Interestingly, these microbially
      experienced T(R) cells suppress tumorigenesis more effectively in recipient mice
      irrespective of their tumor etiology. These data suggest that infections with
      enteric pathogens enhance T(R)-cell potency and protect against epithelial
      cancers later in life, potentially explaining paradoxical increases in cancer
      risk in developed countries having more stringent hygiene practices. The
      possibility that dysregulated gut microbial infections in humans may lead to
      cancer in anatomically distant organs, such as breast, highlights the need for
      novel immune-based strategies in cancer prevention and treatment.

PMID- 16885334
TI  - PIK3CA mutations are an early genetic alteration associated with FGFR3 mutations
      in superficial papillary bladder tumors.
AB  - Bladder tumors constitute a very heterogeneous disease. Superficial tumors are
      characterized by a high prevalence of FGFR3 mutations and chromosome 9
      alterations. High-grade and muscle-invasive tumors are characterized by Tp53
      mutations and aneuploidy. We have analyzed the sequence of exons 9 and 20 of
      PIK3CA in a panel of bladder tumors covering the whole spectrum of the disease.
      DNA from formalin-fixed, paraffin-embedded tumor sections was amplified by PCR
      and products were sequenced. In an unselected panel of tumors representative of
      the disease, the PIK3CA mutation prevalence was 13% (11 of 87). Mutations
      occurred mainly at the previously identified hotspots (codons 542, 545, 1007, and
      1047). The distribution according to stage was as follows: papillary urothelial
      neoplasms of uncertain malignant potential (PUNLMP; 11 of 43, 25.6%), T(a) (9 of
      57, 16%), T(1) (2 of 10, 20%), and muscle-invasive tumors (0 of 20, 0%; P =
      0.019). Mutations were associated with low-grade tumors: grade 1 (6 of 27,
      22.2%), grade 2 (3 of 23, 13%), and grade 3 (2 of 37, 5.4%; P = 0.047). Overall,
      PIK3CA mutations were strongly associated with FGFR3 mutations: 18 of 69 (26%)
      FGFR3(mut) tumors were PIK3CA(mut), versus 4 of 58 (6.9%) FGFR3(wt) tumors (P =
      0.005). Our findings indicate that PIK3CA mutations are a common event that can
      occur early in bladder carcinogenesis and support the notion that papillary and
      muscle-invasive tumors arise through different molecular pathways. PIK3CA may
      constitute a novel diagnostic and prognostic tool, as well as a therapeutic
      target, in bladder cancer.

PMID- 16885335
TI  - Divergent routes to oral cancer.
AB  - Most head and neck squamous cell carcinoma (HNSCC) patients present with late
      stage cancers, which are difficult to treat. Therefore, early diagnosis of high
      risk premalignant lesions and incipient cancers is important. HNSCC is currently
      perceived as a single progression mechanism, resulting in immortal invasive
      cancers. However, we have found that approximately 40% of primary oral SCCs are
      mortal in culture, and these have a better prognosis. About 60% of oral
      premalignancies (dysplasias) are also mortal. The mortal and immortal tumors are
      generated in vivo as judged by p53 mutations and loss of p16(INK4A) expression
      being found only in the original tumors from which the immortal cultures were
      derived. To investigate the relationships of dysplasias to SCCs, we did
      microarray analysis of primary cultures of 4 normal oral mucosa biopsies, 19
      dysplasias, and 16 SCCs. Spectral clustering using the singular value
      decomposition and other bioinformatic techniques showed that development of
      mortal and immortal SCCs involves distinct transcriptional changes. Both SCC
      classes share most of the transcriptional changes found in their respective
      dysplasias but have additional changes. Moreover, high-risk dysplasias that
      subsequently progress to SCCs more closely resemble SCCs than nonprogressing
      dysplasias. This indicates for the first time that there are divergent mortal and
      immortal pathways for oral SCC development via intermediate dysplasias. We
      believe that this new information may lead to new ways of classifying HNSCC in
      relation to prognosis.

PMID- 16885336
TI  - Myopodin-mediated suppression of prostate cancer cell migration involves
      interaction with zyxin.
AB  - Myopodin was identified as a tumor suppressor gene that is frequently deleted in
      aggressive prostate cancer. Expression of myopodin protein suppresses both tumor
      growth and metastasis in vitro and in vivo. In the present study employing a
      yeast two-hybrid system, we found that zyxin, a molecule known to regulate cell
      motility and migration, binds with myopodin with high affinity. The binding
      between zyxin and myopodin seems to be direct. Screening of a series of myopodin
      deletion mutants and peptide competition analyses revealed that myopodin is bound
      by zyxin at a site located within the sequence of the 19 amino acids at the
      myopodin COOH terminus. Importantly, this is the same region where the tumor
      suppressor activity of myopodin is located. The motility and invasion suppression
      activity of myopodin were significantly weakened in myopodin mutants lacking this
      sequence. Thus, our studies suggest that zyxin may be a critical functional
      regulator of myopodin.

PMID- 16885337
TI  - Epigenetic inactivation of the dioxin-responsive cytochrome P4501A1 gene in human
      prostate cancer.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD; dioxin) is a toxic environmental
      contaminant that works through dioxin response elements (DRE) to activate gene
      expression. We tested the hypothesis that cancer-related epigenetic changes
      suppress dioxin activation of the cytochrome P4501A1 (CYP1A1) gene. 5-Aza-2'
      deoxycytidine (5-aza-CdR), an inhibitor of DNA methylation, increases TCDD
      inducible CYP1A1 mRNA expression in cancerous LNCaP cells but not in noncancerous
      PWR-1E and RWPE-1 cells (all human prostate cell lines). Bisulfite DNA sequencing
      shows that the TCDD-responsive CYP1A1 enhancer is highly methylated in LNCaP
      cells but not in RWPE-1 cells. In vivo footprinting experiments reveal that
      unmethylated DRE sites do not bind protein in response to TCDD in LNCaP cells,
      whereas inducible DRE occupancy occurs in RWPE-1 cells. Pretreatment of LNCaP
      cells with 5-aza-CdR partially restores TCDD-inducible DRE occupancy, showing
      that DNA methylation indirectly suppresses DRE occupancy. Chromatin
      immunoprecipitation experiments reveal that LNCaP cells lack trimethyl histone H3
      lysine 4, a mark of active genes, on the CYP1A1 regulatory region, whereas this
      histone modification is prevalent in PWR-1E and RWPE-1 cells. We also analyzed
      CYP1A1 enhancer methylation in human prostate tissue DNA. We do not detect CYP1A1
      enhancer methylation in 30 DNA samples isolated from noncancerous prostate
      tissue. In contrast, 11 of 30 prostate tumor DNA samples have detectable CYP1A1
      enhancer methylation, indicating that it is hypermethylated in prostate tumors.
      This is the first report that shows that CYP1A1 is aberrantly hypermethylated in
      human prostate cancer and has an altered, inaccessible chromatin structure that
      suppresses its dioxin responsiveness.

PMID- 16885338
TI  - High-grade glioma formation results from postnatal pten loss or mutant epidermal
      growth factor receptor expression in a transgenic mouse glioma model.
AB  - High-grade gliomas are devastating brain tumors associated with a mean survival
      of <50 weeks. Two of the most common genetic changes observed in these tumors are
      overexpression/mutation of the epidermal growth factor receptor (EGFR) vIII and
      loss of PTEN/MMAC1 expression. To determine whether somatically acquired EGFRvIII
      expression or Pten loss accelerates high-grade glioma development, we used a
      previously characterized RasB8 glioma-prone mouse strain, in which these specific
      genetic changes were focally introduced at 4 weeks of age. We show that both
      postnatal EGFRvIII expression and Pten inactivation in RasB8 mice potentiate high
      grade glioma development. Moreover, we observe a concordant loss of Pten and EGFR
      overexpression in nearly all high-grade gliomas induced by either EGFRvIII
      introduction or Pten inactivation. This novel preclinical model of high-grade
      glioma will be useful in evaluating brain tumor therapies targeted to the
      pathways specifically dysregulated by EGFR expression or Pten loss.

PMID- 16885339
TI  - Impaired notch signaling promotes de novo squamous cell carcinoma formation.
AB  - Signaling through Notch receptors in the skin has been implicated in the
      differentiation, proliferation, and survival of keratinocytes, as well as in the
      pathogenesis of basal cell carcinoma (BCC). To determine the composite function
      of Notch receptor-mediated signaling in the skin and overcome potential
      redundancies between receptors, conditional transgenic mice were generated that
      express the pan-Notch inhibitor, dominant-negative Mastermind Like 1 (DNMAML1),
      to repress all canonical [CBF-1/Suppressor of hairless/LAG-1 (CSL)-dependent]
      Notch signaling exclusively in the epidermis. Here, we report that DNMAML1 mice
      display hyperplastic epidermis and spontaneously develop cutaneous squamous cell
      carcinoma (SCC) as well as dysplastic precursor lesions, actinic keratoses. Mice
      expressing epidermal DNMAML1 display enhanced accumulation of nuclear beta
      catenin and cyclin D1 in suprabasilar keratinocytes and in lesional cells from
      SCCs, which was also observed in human cutaneous SCC. These results suggest a
      model wherein CSL-dependent Notch signaling confers protection against cutaneous
      SCC. The demonstration that inhibition of canonical Notch signaling in mice leads
      to spontaneous formation of SCC and recapitulates the disease in humans yields
      fundamental insights into the pathogenesis of SCC and provides a unique in vivo
      animal model to examine the pathobiology of cutaneous SCC and for evaluating
      novel therapies.

PMID- 16885341
TI  - Misexpression of full-length HMGA2 induces benign mesenchymal tumors in mice.
AB  - The high-mobility group AT-hook 2 (HMGA2) protein is a member of the high
      mobility group family of the DNA-binding architectural factors and participates
      in the conformational regulation of active chromatin on its specific downstream
      target genes. HMGA2 is expressed in the undifferentiated mesenchyme and is
      undetectable in their differentiated counterparts, suggesting its functional
      importance in mesenchymal cellular proliferation and differentiation.
      Interestingly, it is a frequent target of chromosomal translocations in several
      types of human benign differentiated mesenchymal tumors, including lipomas,
      fibroadenomas of the breast, salivary gland adenomas, and endometrial polyps. The
      translocations lead to a variety of HMGA2 transcripts, which range from wild
      type, truncated, and fusion mRNA species. However, it is not clear whether
      alteration of the HMGA2 transcript is required for its tumorigenic potential. To
      determine whether misexpression of HMGA2 in differentiated mesenchymal cells is
      sufficient to cause tumorigenesis, we produced transgenic mice that misexpressed
      full-length or truncated human HMGA2 transcript under the control of the
      differentiated mesenchymal cell (adipocyte)-specific promoter of the adipocyte P2
      (Fabp4) gene. Expression of the full-length HMGA2 transgene was observed in a
      number of tissues, which produced neoplastic phenotype, including fibroadenomas
      of the breast and salivary gland adenomas. Furthermore, transgenic misexpression
      of the truncated version of HMGA2, containing only the three DNA-binding domains,
      produced similar phenotypes. These results show that misexpression of HMGA2 in a
      differentiated mesenchymal cell is sufficient to cause mesenchymal tumorigenesis
      and is independent of the nature of the HMGA2 transcript that results from
      chromosomal translocations observed in humans.

PMID- 16885340
TI  - Notch pathway inhibition depletes stem-like cells and blocks engraftment in
      embryonal brain tumors.
AB  - The Notch signaling pathway is required in both nonneoplastic neural stem cells
      and embryonal brain tumors, such as medulloblastoma, which are derived from such
      cells. We investigated the effects of Notch pathway inhibition on medulloblastoma
      growth using pharmacologic inhibitors of gamma-secretase. Notch blockade
      suppressed expression of the pathway target Hes1 and caused cell cycle exit,
      apoptosis, and differentiation in medulloblastoma cell lines. Interestingly,
      viable populations of better-differentiated cells continued to grow when Notch
      activation was inhibited but were unable to efficiently form soft-agar colonies
      or tumor xenografts, suggesting that a cell fraction required for tumor
      propagation had been depleted. It has recently been hypothesized that a small
      population of stem-like cells within brain tumors is required for the long-term
      propagation of neoplastic growth and that CD133 expression and Hoechst dye
      exclusion (side population) can be used to prospectively identify such tumor
      forming cells. We found that Notch blockade reduced the CD133-positive cell
      fraction almost 5-fold and totally abolished the side population, suggesting that
      the loss of tumor-forming capacity could be due to the depletion of stem-like
      cells. Notch signaling levels were higher in the stem-like cell fraction,
      providing a potential mechanism for their increased sensitivity to inhibition of
      this pathway. We also observed that apoptotic rates following Notch blockade were
      almost 10-fold higher in primitive nestin-positive cells as compared with nestin
      negative ones. Stem-like cells in brain tumors thus seem to be selectively
      vulnerable to agents inhibiting the Notch pathway.

PMID- 16885342
TI  - Haploinsufficiency in DNA polymerase beta increases cancer risk with age and
      alters mortality rate.
AB  - This study uses a base excision repair (BER)-deficient model, the DNA polymerase
      beta heterozygous mouse, to investigate the effect of BER deficiency on
      tumorigenicity and aging. Aged beta-pol(+/-) mice express 50% less beta-pol
      transcripts and protein (P < 0.05) than aged beta-pol(+/+) mice, showing
      maintenance of the heterozygous state over the life span of the mouse. This
      reduction in beta-pol expression was not associated with an increase in mutation
      rate but was associated with a 100% increase in the onset of hypoploidy. Aged
      beta-pol(+/-) mice exhibited a 6.7-fold increase in developing lymphoma (P <
      0.01). Accordingly, 38% of beta-pol(+/-) mice exhibited lymphoid hyperplasia,
      whereas none of the beta-pol(+/+) exhibited this phenotype. beta-pol(+/-) mice
      were also more likely to develop adenocarcinoma (2.7-fold increase; P < 0.05) and
      more likely to develop multiple tumors, as 20% of the beta-pol(+/-) animals died
      bearing multiple tumors compared with only 5% of the beta-pol(+/+) animals (P <
      0.05). In spite of accelerated tumor development, no gross effect of beta-pol
      heterozygosity was seen with respect to life span. However, the survival curves
      for the beta-pol(+/+) and beta-pol(+/-) mice are not identical. A maximum
      likelihood estimation analysis showed a modest but significant (P < 0.05)
      acceleration of the age-dependent mortality rate in beta-pol(+/-) mice. Thus, the
      beta-pol(+/-) mouse represents a model in which mortality rate and tumor
      development are accelerated and provides evidence supporting the role of genomic
      maintenance in both aging and carcinogenesis.

PMID- 16885343
TI  - Gene expression signatures for predicting prognosis of squamous cell and
      adenocarcinomas of the lung.
AB  - Non-small-cell lung cancers (NSCLC) compose 80% of all lung carcinomas with
      squamous cell carcinomas (SCC) and adenocarcinoma representing the majority of
      these tumors. Although patients with early-stage NSCLC typically have a better
      outcome, 35% to 50% will relapse within 5 years after surgical treatment. We have
      profiled primary squamous cell lung carcinomas from 129 patients using Affymetrix
      U133A gene chips. Unsupervised analysis revealed two clusters of SCC that had no
      correlation with tumor stage but had significantly different overall patient
      survival (P = 0.036). The high-risk cluster was most significantly associated
      with down-regulation of epidermal development genes. Cox proportional hazard
      models identified an optimal set of 50 prognostic mRNA transcripts using a 5-fold
      cross-validation procedure. Quantitative reverse transcription-PCR and
      immunohistochemistry using tissue microarrays were used to validate individual
      gene candidates. This signature was tested in an independent set of 36 SCC
      samples and achieved 84% specificity and 41% sensitivity with an overall
      predictive accuracy of 68%. Kaplan-Meier analysis showed clear stratification of
      high-risk and low-risk patients [log-rank P = 0.04; hazard ratio (HR), 2.66; 95%
      confidence interval (95% CI), 1.01-7.05]. Finally, we combined the SCC classifier
      with our previously identified adenocarcinoma prognostic signature and showed
      that the combined classifier had a predictive accuracy of 71% in 72 NSCLC samples
      also showing significant differences in overall survival (log-rank P = 0.0002;
      HR, 3.54; 95% CI, 1.74-7.19). This prognostic signature could be used to identify
      patients with early-stage high-risk NSCLC who might benefit from adjuvant therapy
      following surgery.

PMID- 16885344
TI  - ROS fusion tyrosine kinase activates a SH2 domain-containing phosphatase
      2/phosphatidylinositol 3-kinase/mammalian target of rapamycin signaling axis to
      form glioblastoma in mice.
AB  - Glioblastoma multiforme is the most common and lethal form of primary brain
      cancer. Diagnosis of this advanced glioma has a poor prognosis due to the
      ineffectiveness of current therapies. Aberrant expression of receptor tyrosine
      kinases (RTK) in glioblastoma multiformes is suggestive of their role in
      initiation and maintenance of these tumors of the central nervous system. In
      fact, ectopic expression of the orphan RTK ROS is a frequent event in human brain
      cancers, yet the pathologic significance of this expression remains undetermined.
      Here, we show that a glioblastoma-associated, ligand-independent rearrangement
      product of ROS (FIG-ROS) cooperates with loss of the tumor suppressor gene locus
      Ink4a;Arf to produce glioblastomas in the mouse. We show that this FIG-ROS
      mediated tumor formation in vivo parallels the activation of the tyrosine
      phosphatase SH2 domain-containing phosphatase-2 (SHP-2) and a
      phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin signaling axis in
      tumors and tumor-derived cell lines. We have established a fully penetrant
      preclinical model for adult onset of glioblastoma multiforme in keeping with
      major genetic events observed in the human disease. These findings provide novel
      and important insights into the role of ROS and SHP-2 function in solid tumor
      biology and set the stage for preclinical testing of targeted therapeutic
      approaches.

PMID- 16885345
TI  - Real-time evaluation of p53 oscillatory behavior in vivo using bioluminescent
      imaging.
AB  - p53 is a key mediator of cellular response to stress, and, although its function
      has been carefully evaluated in vitro, noninvasive evaluation of the
      transcriptional activity of p53 in live animals has not been reported. To this
      end, we developed a transgenic mouse model wherein the firefly luciferase gene
      expression was dependent on the p53-responsive P2 promoter from the murine double
      minute 2 (MDM2) gene. Bioluminescence activity following ionizing radiation was
      shown to be dose, time, and p53 dependent. In addition, expression of both p53
      and its activated form as well as the expression of p53 target genes (MDM2 and
      p21) correlated with bioluminescence activity. Temporal evaluation of p53
      activity following ionizing radiation showed a distinct oscillatory pattern,
      which confirmed the oscillations observed previously in cultured cells. In
      addition, the kinetics of oscillations were altered by pretreatment with
      radiation-modifying agents. These results show the use of this mouse model in
      enhancing our understanding of the transcriptional role of p53 in vivo.

PMID- 16885346
TI  - Epigenomic profiling reveals novel and frequent targets of aberrant DNA
      methylation-mediated silencing in malignant glioma.
AB  - Malignant glioma is the most common central nervous system tumor of adults and is
      associated with a significant degree of morbidity and mortality. Gliomas are
      highly invasive and respond poorly to conventional treatments. Gliomas, like
      other tumor types, arise from a complex and poorly understood sequence of genetic
      and epigenetic alterations. Epigenetic alterations leading to gene silencing, in
      the form of aberrant CpG island promoter hypermethylation and histone
      deacetylation, have not been thoroughly investigated in brain tumors, and
      elucidating such changes is likely to enhance our understanding of their etiology
      and provide new treatment options. We used a combined approach of pharmacologic
      inhibition of DNA methylation and histone deacetylation, coupled with expression
      microarrays, to identify novel targets of epigenetic silencing in glioma cell
      lines. From this analysis, we identified >160 genes up-regulated by 5-aza-2'
      deoxycytidine and trichostatin A treatment. Further characterization of 10 of
      these genes, including the putative metastasis suppressor CST6, the apoptosis
      inducer BIK, and TSPYL5, whose function is unknown, revealed that they are
      frequent targets of epigenetic silencing in glioma cell lines and primary tumors
      and suppress glioma cell growth in culture. Furthermore, we show that other
      members of the TSPYL gene family are epigenetically silenced in gliomas and
      dissect the contribution of individual DNA methyltransferases to the aberrant
      promoter hypermethylation events. These studies, therefore, lay the foundation
      for a comprehensive understanding of the full extent of epigenetic changes in
      gliomas and how they may be exploited for therapeutic purposes.

PMID- 16885347
TI  - MLH3 mutation in endometrial cancer.
AB  - MLH3 is a recently described member of the DNA mismatch repair gene family. Based
      on its interaction with the MutL homologue MLH1, it was postulated that MLH3
      might play a role in tumorigenesis. Germ line and somatic mutations in MLH3 have
      been identified in a small fraction of colorectal cancers, but the role of MLH3
      in colorectal cancer tumorigenesis remains controversial. We investigated MLH3's
      role in endometrial tumorigenesis through analysis of tumor and germ line DNA
      from 57 endometrial cancer patients who were at increased risk for having
      inherited cancer susceptibility. Patients with known MSH2 or MSH6 mutations were
      excluded as well as those who had MLH1-methylated tumors. Sixteen different
      variants were identified by single-strand conformational variant analysis. Of the
      12 missense changes identified, three were somatic mutations. One patient had a
      germ line missense variant and loss of heterozygosity (LOH) in her tumor
      specimen. There was no evidence of MLH3 promoter methylation based on combined
      bisulfite restriction analysis. The identification of inherited missense
      variants, somatic missense mutations (present in 3 of 57 tumors), and LOH in the
      tumor from a patient with a germ line missense change suggest a role for MLH3 in
      endometrial tumorigenesis.

PMID- 16885348
TI  - Cyclin-dependent kinase 5 activity controls cell motility and metastatic
      potential of prostate cancer cells.
AB  - We show here that cyclin-dependent kinase 5 (CDK5), a known regulator of
      migration in neuronal development, plays an important role in prostate cancer
      motility and metastasis. P35, an activator of CDK5 that is indicative of its
      activity, is expressed in a panel of human and rat prostate cancer cell lines,
      and is also expressed in 87.5% of the human metastatic prostate cancers we
      examined. Blocking of CDK5 activity with a dominant-negative CDK5 construct,
      small interfering RNA, or roscovitine resulted in changes in the microtubule
      cytoskeleton, loss of cellular polarity, and loss of motility. Expression of a
      dominant-negative CDK5 in the highly metastatic Dunning AT6.3 prostate cancer
      cell line also greatly impaired invasive capacity. CDK5 activity was important
      for spontaneous metastasis in vivo; xenografts of AT6.3 cells expressing dominant
      negative CDK5 had less than one-fourth the number of lung metastases exhibited by
      AT6.3 cells expressing the empty vector. These results show that CDK5 activity
      controls cell motility and metastatic potential in prostate cancer.

PMID- 16885349
TI  - SPARC represses E-cadherin and induces mesenchymal transition during melanoma
      development.
AB  - During progression of melanoma, loss of the cell-cell adhesion molecule E
      cadherin contributes to uncontrolled growth and invasive behavior of transformed
      melanocytes. Secreted protein acidic and rich in cysteine (SPARC) is a
      nonstructural matricellular protein that regulates cell-matrix interactions
      leading to alterations in cell adhesion and proliferation. Overexpression of
      SPARC has been associated with progression of various cancers, including
      melanoma; however, its role in primary tumor development is not well defined. We
      show that normal human melanocytes overexpressing SPARC adopt a fibroblast-like
      morphology, concomitant with loss of E-cadherin and P-cadherin expression, and
      increased expression of mesenchymal markers. Concurrent with these changes, SPARC
      expression stimulates melanocyte motility and melanoma cell invasion. Expression
      of SPARC results in transcriptional down-regulation of E-cadherin that correlates
      with induction of Snail, a repressor of E-cadherin. Conversely, SPARC depletion
      leads to up-regulation of E-cadherin and reduces Snail levels, and SPARC-null
      cells exhibit a marked change in their mesenchymal phenotype. Finally, analysis
      of SPARC, Snail, and E-cadherin levels in melanocytes and malignant melanoma cell
      lines further supports the functional relationship among these proteins during
      melanoma progression. Our findings provide evidence for the role of SPARC in
      early transformation of melanocytes and identify a novel mechanism, whereby tumor
      derived SPARC promotes tumorigenesis by mediating Snail induction and E-cadherin
      suppression.

PMID- 16885351
TI  - A photon counting technique for quantitatively evaluating progression of
      peritoneal tumor dissemination.
AB  - We recently established a mouse model of peritoneal dissemination of human
      gastric carcinoma, including the formation of ascites, by orthotopic
      transplantation of cultured gastric carcinoma cells. To clarify the processes of
      expansion of the tumors in this model, nude mice were sacrificed and autopsied at
      different points of time after the orthotopic transplantation of the cancer cells
      for macroscopic and histopathologic examination of the tumors. The cancer cells
      grew actively in the gastric submucosa and invaded the deeper layers to reach the
      serosal plane. The tumor cells then underwent exfoliation and became free
      followed by the formation of metastatic lesions initially in the greater omentum
      and subsequent colonization and proliferation of the tumors on the peritoneum.
      Although this model allowed the detection of even minute metastases, it was not
      satisfactory from the viewpoint of quantitative and objective evaluation. To
      resolve these problems, we introduced a luciferase gene into this tumor cell line
      with a high metastasizing potential and carried out in vivo photon counting
      analysis. This photon counting technique was found to allow objective and
      quantitative evaluation of the progression of peritoneal dissemination on a real
      time basis. This animal metastatic model is useful for monitoring the responses
      of tumors to anticancer agents.

PMID- 16885350
TI  - Helicobacter pylori can induce heparin-binding epidermal growth factor expression
      via gastrin and its receptor.
AB  - Both gastrin and Helicobacter pylori have been shown capable of up-regulating
      gene expression and protein shedding of heparin-binding epidermal growth factor
      (HB-EGF). Furthermore, the bacteria have previously been shown to induce serum
      hypergastrinemia in infected individuals. The aim of this work was to assess the
      extent to which the ability of H. pylori to up-regulate expression of HB-EGF can
      be attributed to its effect on gastrin. Gastric cells, transfected with either
      gastrin small interfering RNA or antisense plasmid or the gastrin/cholecystokinin
      2 receptor (CCK-2R), were cultured for 24 hours with H. pylori(+/-), a CCK-2R
      antagonist. Gene expression levels were measured using reverse transcription-PCR,
      whereas protein changes were measured using ELISA, Western blotting, and
      immunofluorescence. H. pylori induced significantly higher levels of HB-EGF gene
      expression and ectodomain shedding in the CCK-2R-transfected cells than the
      vector control (P < 0.01). Addition of the CCK-2R inhibitor significantly
      decreased gene and shedding up-regulation. Gastrin down-regulation reduced the
      effect of the bacteria on HB-EGF gene and protein expression levels. Endogenous
      gastrin and CCK-2R expression were also found to be significantly up-regulated in
      all cell lines as a result of exposure to H. pylori (P < 0.02). Gastric mucosal
      tissue from H. pylori-infected individuals had significantly higher CCK-2R
      expression levels than noninfected (P < 0.003), and in hypergastrinemic mice,
      there was an increase in HB-EGF-expressing cells in the gastric mucosa and
      colocalization of HB-EGF with CCK-2R-positive enterochromaffin-like cells. In
      conclusion, gastrin and the CCK-2R play significant roles in the induction of HB
      EGF gene and protein expression and ectodomain shedding by H. pylori.

PMID- 16885353
TI  - The hedgehog signaling molecule Gli2 induces parathyroid hormone-related peptide
      expression and osteolysis in metastatic human breast cancer cells.
AB  - Parathyroid hormone-related peptide (PTHrP) is a major factor involved in tumor
      induced osteolysis caused by breast cancers that have metastasized to bone.
      However, the molecular mechanisms that mediate PTHrP production by breast cancer
      cells are not entirely clear. We hypothesized that Gli2, a downstream
      transcriptional effector of the Hedgehog (Hh) signaling pathway, regulates PTHrP
      expression in metastatic breast cancer because the Hh pathway regulates
      physiologic PTHrP expression in the developing growth plate. Here, we show that
      Gli2 is expressed in several human cancer cell lines that cause osteolytic
      lesions in vivo and produce PTHrP (MDA-MB-231, RWGT2, and PC-3) but is not
      expressed in nonosteolytic cancer cell lines that do not secrete PTHrP (MCF-7, ZR
      75, and T47D). Transient expression of Gli2 in MDA-MB-231 and MCF-7 breast cancer
      cells increased PTHrP promoter-luciferase activity dose dependently. Stable
      expression of Gli2 in MDA-MB-231 cells resulted in an increase in PTHrP protein
      in the conditioned medium. Alternatively, MDA-MB-231 cells stably transfected
      with Gli2-EnR, a repressor of Gli2 activity, exhibited a 72% to 93% decrease in
      PTHrP mRNA by quantitative real-time PCR when compared with control cells. To
      examine the effects of Gli2 on breast cancer-mediated osteolysis in vivo, athymic
      nude mice were inoculated with MDA-MB-231 cells stably expressing Gli2 or the
      empty vector. Following tumor cell inoculation via the left cardiac ventricle,
      Gli2-expressing tumors caused significantly more osteolysis. Together, these data
      suggest that PTHrP expression and osteolysis in vivo in human breast cancer cells
      is driven at least in part by Gli2.

PMID- 16885354
TI  - A novel functional polymorphism in the transforming growth factor-beta2 gene
      promoter and tumor progression in breast cancer.
AB  - Transforming growth factor-beta (TGF-beta), a multifunctional growth factor,
      plays an important role in breast cancer. There is increasing evidence that
      enhanced expression of TGF-beta promotes breast cancer progression contributing
      to metastasis and invasiveness of the tumor. We identified a functional
      polymorphism in the TGFB2 promoter, a 4-bp insertion at position -246 relative to
      the transcriptional start site (-246ins). Transient transfection experiments
      showed that the -246ins polymorphism significantly increased TGFB2 promoter
      activity in breast cancer cells. Electrophoretic mobility shift assays revealed
      binding of the transcription factor Sp1 to the -246ins allele. Overexpression of
      Sp1 enhanced promoter activity of the -246ins allele, demonstrating that Sp1
      mediates transcriptional activation. Furthermore, the -246ins allele was
      associated with enhanced TGF-beta(2) expression in breast cancer tissue (P =
      0.0005). To evaluate the role of the polymorphism in breast cancer, frequency of
      the -246ins allele was determined in breast cancer patients (n = 78) and healthy
      female controls (n = 143). No significant differences were found. However, the
      presence of the -246ins allele was associated with lymph node metastasis (P =
      0.003). The -246ins allele was a significant predictor for lymph node metastasis
      independent of estrogen and progesterone receptor status in a multivariate
      logistic regression analysis (P = 0.0118, odds ratio, 5.18; 95% confidence
      interval, 1.44-18.62). We provide evidence that the TGFB2 -246ins polymorphism
      leads to enhanced TGF-beta(2) expression levels in vivo and might thereby
      contribute to tumor progression and development of metastases.

PMID- 16885352
TI  - p38gamma mitogen-activated protein kinase integrates signaling crosstalk between
      Ras and estrogen receptor to increase breast cancer invasion.
AB  - Ras is believed to stimulate invasion and growth by different effector pathways,
      and yet, the existence of such effectors under physiologic conditions has not
      been shown. Estrogen receptor (ER), on the other hand, is both anti-invasive and
      proliferative in human breast cancer, with mechanisms for these paradoxical
      actions remaining largely unknown. Our previous work showed an essential role of
      p38gamma mitogen-activated protein kinase in Ras transformation in rat intestinal
      epithelial cells, and here, we show that p38gamma integrates invasive antagonism
      between Ras and ER to increase human breast cancer invasion without affecting
      their proliferative activity. Ras positively regulates p38gamma expression, and
      p38gamma in turn mediates Ras nonmitogenic signaling to increase invasion.
      Expression of the Ras/p38gamma axis, however, is trans-suppressed by ER that
      inhibits invasion and stimulates growth also by distinct mechanisms. Analysis of
      ER and its cytoplasmic localized mutant reveals that ER additionally binds to
      p38gamma protein, leading to its specific down-regulation in the nuclear
      compartment. A p38gamma-antagonistic activity of ER was further shown in a panel
      of breast cancer cell lines and was shown independent of estrogens by both ER
      depletion and ER expression. These results revealed that both Ras and ER use
      distinct pathways to regulate breast cancer growth and invasion, and that
      p38gamma specifically integrates their antagonistic activity to stimulate cell
      invasion. Selective targeting of p38gamma-dependent invasion pathways may be a
      novel strategy to control breast cancer progression.

PMID- 16885355
TI  - Notch1-induced transformation of RKE-1 cells requires up-regulation of cyclin D1.
AB  - RKE-1 cells induced to overexpress activated Notch1 (RKE-ER-N(ic)) exhibit
      increased cyclin D1 transcripts and become transformed. However, the oncogenic
      pathway of Notch1-induced transformation is not known. Here, we use mutational
      analysis to functionally identify the sole region of the cyclin D1 promoter that
      responds to activated Notch1. The same region responds to activated Notch4 as
      well as to physiologic Notch ligand-induced Notch receptor signaling. The cyclin
      D1 gene was subsequently found to be a physiologic target of Notch signaling in
      Pofut1(-/-) mouse embryos defective in canonical Notch signaling and in embryos
      with an inactivating mutation in Notch1. To determine if Notch1-induced cyclin D1
      expression in RKE-ER-N(ic) cells plays a direct role in transformation, cyclin D1
      up-regulation was inhibited using a cyclin D1 antisense cDNA. We report here that
      transformation of RKE-ER-N(ic) cells is dependent on increased expression of
      cyclin D1 protein, which represents a new mechanism of Notch1-induced
      transformation.

PMID- 16885356
TI  - Up-regulation of CYP26A1 in adenomatous polyposis coli-deficient vertebrates via
      a WNT-dependent mechanism: implications for intestinal cell differentiation and
      colon tumor development.
AB  - Mutations in the adenomatous polyposis coli (APC) tumor suppressor gene seem to
      underlie the initiation of many colorectal carcinomas. Loss of APC function
      results in accumulation of beta-catenin and activation of beta-catenin/TCF
      dependent transcription. Recent studies have implicated APC in controlling
      retinoic acid biosynthesis during normal intestinal development through a WNT
      independent mechanism. Paradoxically, however, previous studies found that
      dietary supplementation of Apc(MIN) mice with retinoic acid failed to abrogate
      adenoma formation. While investigating the above finding, we found that
      expression of CYP26A1, a major retinoic acid catabolic enzyme, was up-regulated
      in Apc(MIN) mouse adenomas, human FAP adenomas, human sporadic colon carcinomas,
      and in the intestine of apc(mcr) mutant zebrafish embryos. Mechanistically,
      cyp26a1 induction following apc mutation is dependent on WNT signaling as
      antisense morpholino knockdown of tcf4 or injection of a dnLEF construct into
      apc(mcr) mutant zebrafish suppressed expression of cyp26a1 along with known WNT
      target genes. In addition, injection of stabilized beta-catenin or dnGSK3beta
      into wild-type embryos induced cyp26a1 expression. Genetic knockdown or
      pharmacologic inhibition of cyp26a1 in apc(mcr) mutant zebrafish embryos rescued
      gut differentiation defects such as expression of intestinal fatty acid-binding
      protein and pancreatic trypsin. These findings support a novel role for APC in
      balancing retinoic acid biosynthesis and catabolism through WNT-independent and
      WNT-dependent mechanisms.

PMID- 16885357
TI  - Activator protein-1 activity regulates epithelial tumor cell identity.
AB  - To examine the consequences of inhibiting activator protein-1 (AP-1)
      transcription factors in skin, transgenic mice were generated, which use the
      tetracycline system to conditionally express A-FOS, a dominant negative that
      inhibits AP-1 DNA binding. Older mice develop mild alopecia and hyperplasia of
      sebaceous glands, particularly around the eyes. When A-FOS was expressed during
      chemical-induced skin carcinogenesis, mice do not develop characteristic benign
      and malignant squamous lesions but instead develop benign sebaceous adenomas
      containing a signature mutation in the H-ras proto-oncogene. Inhibiting AP-1
      activity after tumor formation caused squamous tumors to transdifferentiate into
      sebaceous tumors. Furthermore, reactivating AP-1 in sebaceous tumors results in a
      reciprocal transdifferentiation into squamous tumors. In both cases of
      transdifferentiation, individual cells express molecular markers for both cell
      types, indicating individual tumor cells have the capacity to express multiple
      lineages. Molecular characterization of cultured keratinocytes and tumor material
      indicates that AP-1 regulates the balance between the wnt/beta-catenin and
      hedgehog signaling pathways that determine squamous and sebaceous lineages,
      respectively. Chromatin immunoprecipitation analysis indicates that c-Jun binds
      several wnt promoters, which are misregulated by A-FOS expression, suggesting
      that members of the wnt pathway can be a primary targets of AP-1 transcriptional
      regulation. Thus, AP-1 activity regulates tumor cell lineage and is essential to
      maintain the squamous tumor cell identity.

PMID- 16885358
TI  - Loss of p63 leads to increased cell migration and up-regulation of genes involved
      in invasion and metastasis.
AB  - p63, a homologue of the tumor suppressor p53, is critical for the development and
      maintenance of squamous epithelia. p63 is specifically expressed in the basal
      layers of stratified epithelial tissues and is considered a specific marker for
      cells of this type. The role of p63 in tumorigenesis remains poorly defined.
      Numerous studies have highlighted the oncogenic potential of the predominant p63
      isoform DeltaNp63alpha; however, data suggest that other p63 proteins can act as
      tumor suppressors or alter the metastatic potential of tumors. DeltaNp63alpha can
      act as a transcriptional repressor, but the link between the transcriptional
      functions of p63 and its biological role is still unclear. In this study, we used
      a loss-of-function approach to investigate the transcriptional programs
      controlled by p63. Disruption of p63 in squamous cell lines resulted in down
      regulation of transcripts specifically expressed in squamous tissues and a
      significant alteration of keratinocyte differentiation. Interestingly, we found
      that disruption of p63 led to up-regulation of markers of nonepithelial tissues
      (mesenchyme and neural tissue) in both primary and immortalized squamous cells.
      Many of these up-regulated genes are associated with increased capacity for
      invasion and metastasis in tumors. Furthermore, loss of p63 expression was
      accompanied by a shift toward mesenchymal morphology and an increase in motility
      in primary keratinocytes and squamous cell lines. We conclude that loss of
      endogenous p63 expression results in up-regulation of genes associated with
      invasion and metastasis, and predisposes to a loss of epithelial and acquisition
      of mesenchymal characteristics. These findings have implications for the role of
      p63 in both development and tumorigenesis.

PMID- 16885359
TI  - Combined effect of proteasome and calpain inhibition on cisplatin-resistant human
      melanoma cells.
AB  - Resistance of tumor cells to cisplatin is a common feature frequently encountered
      during chemotherapy against melanoma caused by various known and unknown
      mechanisms. To overcome drug resistance toward cisplatin, a targeted treatment
      using alternative agents, such as proteasome inhibitors, has been investigated.
      This combination could offer a new therapeutic approach. Here, we report the
      biological effects of proteasome inhibitors on the parental cisplatin-sensitive
      MeWo human melanoma cell line and its cisplatin-resistant MeWo(cis1) variant. Our
      experiments show that proteasome inhibitor treatment of both cell lines impairs
      cell viability at concentrations that are not toxic to primary human fibroblasts
      in vitro. However, compared with the parental MeWo cell line, significantly
      higher concentrations of proteasome inhibitor are required to reduce cell
      viability of MeWo(cis1) cells. Moreover, whereas proteasome activity was
      inhibited to the same extent in both cell lines, IkappaBalpha degradation and
      nuclear factor-kappaB (NF-kappaB) activation in MeWo(cis1) cells was proteasome
      inhibitor independent but essentially calpain inhibitor sensitive. In support, a
      calpain-specific inhibitor impaired NF-kappaB activation in MeWo(cis1) cells.
      Here, we show that cisplatin resistance in MeWo(cis1) is accompanied by a change
      in the NF-kappaB activation pathway in favor of calpain-mediated IkappaBalpha
      degradation. Furthermore, combined exposure to proteasome and calpain inhibitor
      resulted in additive effects and a strongly reduced cell viability of MeWo(cis1)
      cells. Thus, combined strategies targeting distinct proteolytic pathways may help
      to overcome mechanisms of drug resistance in tumor cells.

PMID- 16885360
TI  - Metabolic consequences of p300 gene deletion in human colon cancer cells.
AB  - Metabolite profiling using (1)H nuclear magnetic resonance (NMR) spectroscopy was
      used to investigate the metabolic changes associated with deletion of the gene
      for the transcriptional coactivator p300 in the human colon carcinoma cell line
      HCT116. Multivariate statistical methods were used to distinguish between
      metabolite patterns that were dependent on cell growth conditions and those that
      were specifically associated with loss of p300 function. In the absence of serum,
      wild-type cells showed slower growth, which was accompanied by a marked decrease
      in phosphocholine concentration, which was not observed in otherwise isogenic
      cell lines lacking p300. In the presence of serum, several metabolites were
      identified as being significantly different between the two cell types, including
      glutamate and glutamine, a nicotinamide-related compound and
      glycerophosphocholine (GPC). However, in the absence of serum, these metabolites,
      with the exception of GPC, were not significantly different, leading us to
      conclude that most of these changes were context dependent. Transcript profiling,
      using DNA microarrays, showed changes in the levels of transcripts for several
      enzymes involved in choline metabolism, which might explain the change in GPC
      concentration. Localized in vivo (1)H NMR measurements on the tumors formed
      following s.c. implantation of these cells into mice showed an increase in the
      intensity of the peak from choline-containing compounds in the p300(-) tumors.
      These data show that NMR-based metabolite profiling has sufficient sensitivity to
      identify the metabolic consequences of p300 gene deletion in tumor cells in vitro
      and in vivo.

PMID- 16885361
TI  - Mutation of succinate dehydrogenase subunit C results in increased O2.-,
      oxidative stress, and genomic instability.
AB  - Mutations in genes coding for succinate dehydrogenase (SDH) subunits are believed
      to contribute to cancer and aging, but the mechanism for this is unclear. Hamster
      fibroblasts expressing a mutation in SDH subunit C (SDHC; B9) showed 3-fold
      increases in dihydroethidine and dichlorodihydrofluorescein (CDCFH(2)) oxidation
      indicative of increased steady-state levels of O2(.-) and H2O2, increases in
      glutathione/glutathione disulfide (indicative of oxidative stress), as well as
      increases in superoxide dismutase activity, relative to parental B1 cells. B9
      cells also showed characteristics associated with cancer cells, including
      aneuploidy, increases in glucose consumption, and sensitivity to glucose
      deprivation-induced cytotoxicity. Expression of wild-type (WT) human SDHC in B9
      cells caused prooxidant production, glucose consumption, sensitivity to glucose
      deprivation-induced cytotoxicity, and aneuploidy to revert to the WT phenotype.
      These data show that SDHC mutations cause increased O2(.-) production, metabolic
      oxidative stress, and genomic instability and that mutations in genes coding for
      mitochondrial electron transport chain proteins can contribute to phenotypic
      changes associated with cancer cells. These results also allow for the
      speculation that DNA damage to genes coding for electron transport chain proteins
      could result in a "mutator phenotype" by increasing steady-state levels of O2(.-)
      and H2O2.

PMID- 16885362
TI  - In vivo biological activity of the histone deacetylase inhibitor LAQ824 is
      detectable with 3'-deoxy-3'-[18F]fluorothymidine positron emission tomography.
AB  - Histone deacetylase inhibitors (HDACI) are emerging as growth inhibitory
      compounds that modulate gene expression and inhibit tumor cell proliferation. We
      assessed whether 3'-deoxy-3'-[(18)F]fluorothymidine-positron emission tomography
      ([18F]FLT-PET) could be used to noninvasively measure the biological activity of
      a novel HDACI LAQ824 in vivo. We initially showed that thymidine kinase 1 (TK1;
      EC2.7.1.21), the enzyme responsible for [18F]FLT retention in cells, was
      regulated by LAQ824 in a drug concentration-dependent manner in vitro. In HCT116
      colon carcinoma xenograft-bearing mice, LAQ824 significantly decreased tumor
      [18F]FLT uptake in a dose-dependent manner. At day 4 of treatment, [18F]FLT tumor
      to-heart ratios at 60 minutes (NUV60) were 2.16 +/- 0.15, 1.86 +/- 0.13, and 1.45
      +/- 0.20 in vehicle, and 5 and 25 mg/kg LAQ824 treatment groups, respectively (P
      < or = 0.05). LAQ825 at 5 mg/kg also significantly reduced both TK1 levels and
      [18F]FLT uptake at day 10 but not at day 2 (P < or = 0.05). [18F]FLT NUV60
      correlated significantly with cellular proliferation (r = 0.68; P = 0.0019) and
      was associated with drug-induced histone H4 hyperacetylation. Of interest to
      [18F]FLT-PET imaging, both TK1 mRNA copy numbers and protein levels decreased in
      the order vehicle >5 mg/kg LAQ824 > 25 mg/kg LAQ824, providing a rationale for
      the use of [18F]FLT-PET in this setting. We also observed increases in Rb
      hypophosphorylation and p21 levels, factors that could have contributed to the
      alteration in TK1 transcription in vivo. In conclusion, we have shown the utility
      of [18F]FLT-PET for monitoring the biological activity of the HDACI, LAQ824. Drug
      induced changes in tumor [18F]FLT uptake were due, at least in part, to
      reductions in TK1 transcription and translation.

PMID- 16885363
TI  - Effect of target dynamics on pharmacokinetics of a novel therapeutic antibody
      against the epidermal growth factor receptor: implications for the mechanisms of
      action.
AB  - The epidermal growth factor receptor (EGFR) is overexpressed on many solid tumors
      and represents an attractive target for antibody therapy. Here, we describe the
      effect of receptor-mediated antibody internalization on the pharmacokinetics and
      dose-effect relationship of a therapeutic monoclonal antibody (mAb) against EGFR
      (2F8). This mAb was previously found therapeutically active in mouse tumor models
      by two dose-dependent mechanisms of action: blockade of ligand binding and
      induction of antibody-dependent cell-mediated cytotoxicity. In vitro studies
      showed 2F8 to be rapidly internalized by EGFR-overexpressing cells. In vivo,
      accelerated 2F8 clearance was observed in cynomolgus monkeys at low doses but not
      at high doses. This enhanced clearance seemed to be receptor dependent and was
      included in a pharmacokinetic model designed to explain its nonlinearity.
      Receptor-mediated clearance was also found to affect in situ antibody
      concentrations in tumor tissue. Ex vivo analyses of xenograft tumors of 2F8
      treated nude mice revealed that relatively high antibody plasma concentrations
      were required for maximum EGFR saturation in high-EGFR-expressing human A431
      tumors, in contrast to lower-EGFR-expressing human xenograft tumors. In summary,
      receptor-mediated antibody internalization and degradation provides a saturable
      route of clearance that significantly affects pharmacokinetics, particularly at
      low antibody doses. EGFR saturation in normal tissues does not predict saturation
      in tumor tissue as local antibody concentrations in EGFR-overexpressing tumors
      may be more rapidly reduced by antibody internalization. Consequently, antibody
      saturation of the receptor may be affected, thereby affecting the local mechanism
      of action.

PMID- 16885364
TI  - Determinants of sensitivity and resistance to rapamycin-chemotherapy drug
      combinations in vivo.
AB  - The phosphatidylinositol-3-OH kinase [PI(3)K] pathway is frequently activated in
      human cancers and represents a rational target for therapeutic intervention. We
      have previously shown that enforced expression of Akt, which is a downstream
      effector of PI(3)K, could promote tumorigenesis and drug resistance in the Emu
      myc mouse lymphoma model, and that these tumors were particularly sensitive to
      inhibition of mammalian target of rapamycin (mTOR) with rapamycin when combined
      with conventional chemotherapy. We now show that reduced dosage of PTEN, a
      negative regulator of PI(3)K signaling, is sufficient to activate Akt, but has
      only a modest effect on lymphomagenesis in the same model. Nonetheless, loss of
      even one PTEN allele resulted in lymphomas that were resistant to conventional
      chemotherapy yet sensitive to rapamycin/chemotherapy combinations. These effects
      could be recapitulated by using RNA interference to suppress PTEN expression in
      lymphomas, which were previously established in the absence of PI(3)K lesions.
      Finally, the introduction of lesions that act downstream of mTOR (eIF4E) or
      disable apoptosis (Bcl-2 and loss of p53) into PTEN+/- lymphomas promoted
      resistance to rapamycin/chemotherapy combinations. Thus, whether activation of
      the PI(3)K pathway confers sensitivity or resistance to therapy depends on the
      therapy used as well as secondary genetic events. Understanding these genotype
      response relationships in human tumors will be important for the effective use of
      rapamycin or other compounds targeting the PI(3)K pathway in the clinic.

PMID- 16885365
TI  - Targeted therapy with a Salmonella typhimurium leucine-arginine auxotroph cures
      orthotopic human breast tumors in nude mice.
AB  - We report here a modified auxotrophic strain of Salmonella typhimurium that can
      target and cure breast tumors in orthotopic mouse models. We have previously
      reported development of a genetically modified strain of S. typhimurium, selected
      for prostate tumor targeting and therapy in vivo. The strain, termed S.
      typhimurium A1, selectively grew in prostate tumors in xenograft models causing
      tumor regression. In contrast, normal tissue was cleared of these bacteria even
      in immunodeficient athymic mice with no apparent side effects. A1 is auxotrophic
      (leucine-arginine dependent) but apparently receives sufficient nutritional
      support only from tumor tissue. The ability to grow in viable tumor tissue may
      account, in part, for the unique antitumor efficacy of the strain. In the present
      report, to increase tumor-targeting capability of A1, the strain was reisolated
      after infection of a human colon tumor growing in nude mice. The tumor-isolated
      strain, termed A1-R, had increased targeting for tumor cells in vivo as well as
      in vitro compared with A1. Treatment with A1-R resulted in highly effective tumor
      targeting, including viable tumor tissue and significant tumor shrinkage in mice
      with s.c. or orthotopic human breast cancer xerographs. Survival of the treated
      animals was significantly prolonged. Forty percent of treated mice were cured
      completely and survived as long as non-tumor-bearing mice. These results suggest
      that amino acid auxotrophic virulent bacteria, which selectively infect and
      attack viable tumor tissue, are a promising approach to cancer therapy.

PMID- 16885366
TI  - Epidermal growth factor receptor-related protein inhibits cell growth and
      invasion in pancreatic cancer.
AB  - The epidermal growth factor receptor (EGFR) signaling network plays critical
      roles in human cancers, including pancreatic cancer, suggesting that the
      discovery of specific agents targeting EGFR would be extremely valuable for
      pancreatic cancer therapy. EGFR-related protein (ERRP), a recently identified pan
      erbB inhibitor, has been shown to inhibit growth and induce apoptosis of
      pancreatic cancer cells in vitro and tumor growth in a xenograft model. However,
      the precise molecular mechanism(s) by which ERRP exerts its antitumor activity
      remains unclear. The current investigation was undertaken to delineate the tumor
      growth inhibitory mechanism(s) of ERRP in pancreatic cancer cells. Using multiple
      molecular assays, such as 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide assay, apoptosis, gene transfection, real-time reverse transcription-PCR,
      Western blotting, invasion, and electrophoretic mobility shift assay for
      measuring DNA-binding activity of nuclear factor-kappaB (NF-kappaB), we found
      that ERRP caused marked inhibition of pancreatic cancer cell growth. This was
      accompanied by increased apoptosis and concomitant attenuation of Notch-1 and NF
      kappaB and down-regulation of NF-kappaB downstream genes, such as matrix
      metalloproteinase-9 and vascular endothelial growth factor, resulting in the
      inhibition of pancreatic cancer cell invasion through the Matrigel. We also found
      that down-regulation of Notch-1 by small interfering RNA before ERRP treatment
      resulted in enhanced cell growth inhibition and apoptosis. Our data suggest that
      the ERRP-mediated inactivation of EGFR, Notch-1, NF-kappaB, and its downstream
      target genes contributed to the inhibition of cell growth and invasion. We
      conclude that ERRP could be an effective agent for inhibiting tumor growth and
      invasion for the treatment of pancreatic cancer.

PMID- 16885367
TI  - A novel orally active small molecule potently induces G1 arrest in primary
      myeloma cells and prevents tumor growth by specific inhibition of cyclin
      dependent kinase 4/6.
AB  - Cell cycle deregulation is central to the initiation and fatality of multiple
      myeloma, the second most common hematopoietic cancer, although impaired apoptosis
      plays a critical role in the accumulation of myeloma cells in the bone marrow.
      The mechanism for intermittent, unrestrained proliferation of myeloma cells is
      unknown, but mutually exclusive activation of cyclin-dependent kinase 4 (Cdk4)
      cyclin D1 or Cdk6-cyclin D2 precedes proliferation of bone marrow myeloma cells
      in vivo. Here, we show that by specific inhibition of Cdk4/6, the orally active
      small-molecule PD 0332991 potently induces G(1) arrest in primary bone marrow
      myeloma cells ex vivo and prevents tumor growth in disseminated human myeloma
      xenografts. PD 0332991 inhibits Cdk4/6 proportional to the cycling status of the
      cells independent of cellular transformation and acts in concert with the
      physiologic Cdk4/6 inhibitor p18(INK4c). Inhibition of Cdk4/6 by PD 0332991 is
      not accompanied by induction of apoptosis. However, when used in combination with
      a second agent, such as dexamethasone, PD 0332991 markedly enhances the killing
      of myeloma cells by dexamethasone. PD 0332991, therefore, represents the first
      promising and specific inhibitor for therapeutic targeting of Cdk4/6 in multiple
      myeloma and possibly other B-cell cancers.

PMID- 16885368
TI  - The Aurora kinase inhibitor VX-680 induces endoreduplication and apoptosis
      preferentially in cells with compromised p53-dependent postmitotic checkpoint
      function.
AB  - VX-680 is a potent inhibitor of Aurora kinases that induces the accumulation of
      cells with > or =4N DNA content, followed by cell death. Here, we define the role
      of p53 and p21(Waf1/Cip1) in cell cycle perturbations following exposure to VX
      680. Endoreduplication and apoptosis in response to VX-680 are limited in A549
      and MCF-7 cells expressing wild-type p53, and markedly enhanced in cells lacking
      p53, including those engineered to express the HPV16-E6 oncoprotein or short
      interfering RNA pools targeting p53. In contrast, endoreduplication and apoptosis
      occur in the p53 wild-type cell lines, RKO and U2OS. The difference in response
      to VX-680 among these cell lines correlates with the timing of induction of
      p21(Waf1/Cip1) and its ability to inhibit cyclin E-cdk2 activity. In A549 cells,
      VX-680 induces the expression of p53 and p21(Waf1/Cip1) within 24 hours, with
      consequent inhibition of cyclin E-cdk2, and reduction of retinoblastoma protein
      phosphorylation, limiting endoreduplication. In RKO and U2OS cells, the induction
      of p21(Waf1/Cip1) is delayed and associated with higher residual cyclin E-cdk2
      kinase activity and retinoblastoma protein phosphorylation, followed by
      progressive endoreduplication and apoptosis. Abrogation of p21(Waf1/Cip1)
      expression by short interfering RNA targeting in A549 cells results in a
      substantial increase in the degree of endoreduplication, whereas inducible
      expression of p21(Waf1/Cip1) in p53-negative NCI-H1299 cells inhibits VX-680
      induced endoreduplication and cell death. These data suggest that the integrity
      of the p53-p21(Waf1/Cip1)-dependent postmitotic checkpoint governs the response
      to Aurora kinase inhibition. Although cells with intact checkpoint function
      arrest with 4N DNA content, those with compromised checkpoint function are more
      likely to undergo endoreduplication followed by eventual apoptosis.

PMID- 16885369
TI  - Targeting the heat shock factor 1 by RNA interference: a potent tool to enhance
      hyperthermochemotherapy efficacy in cervical cancer.
AB  - Carcinoma of the uterine cervix is one of the highest causes of mortality in
      female cancer patients worldwide, and improved treatment options for this type of
      malignancy are highly needed. Local hyperthermia has been successfully used in
      combination with systemic administration of cisplatin-based chemotherapy in phase
      I/II clinical studies. Heat-induced expression of cytoprotective and
      antiapoptotic heat shock proteins (HSP) is a known complication of hyperthermia,
      resulting in thermotolerance and chemoresistance and hindering the efficacy of
      the combination therapy. Heat shock transcription factor 1 (HSF1) is the master
      regulator of heat-induced HSP expression. In the present report, we used small
      interfering RNA (siRNA) to silence HSF1 and to examine the effect of HSF1 loss of
      function on the response to hyperthermia and cisplatin-based chemotherapy in HeLa
      cervical carcinoma. We have identified the 322-nucleotide to 340-nucleotide HSF1
      sequence as an ideal target for siRNA-mediated HSF1 silencing, have created a
      pSUPER-HSF1 vector able to potently suppress the HSF1 gene, and have generated
      for the first time human cancer cell lines with stable loss of HSF1 function. We
      report that, although it surprisingly does not affect cancer cell sensitivity to
      cisplatin or elevated temperatures up to 43 degrees C when administered
      separately, loss of HSF1 function causes a dramatic increase in sensitivity to
      hyperthermochemotherapy, leading to massive (>95%) apoptosis of cancer cells.
      These findings indicate that disruption of HSF1-induced cytoprotection during
      hyperthermochemotherapy may represent a powerful strategy to selectively amplify
      the damage in cancer cells and identify HSF1 as a promising therapeutic target in
      cervical carcinoma.

PMID- 16885370
TI  - The DNA N-glycosylase MED1 exhibits preference for halogenated pyrimidines and is
      involved in the cytotoxicity of 5-iododeoxyuridine.
AB  - The base excision repair protein MED1 (also known as MBD4), an interactor with
      the mismatch repair protein MLH1, has a central role in the maintenance of
      genomic stability with dual functions in DNA damage response and repair. MED1
      acts as a thymine and uracil DNA N-glycosylase on T:G and U:G mismatches that
      occur at cytosine-phosphate-guanine (CpG) methylation sites due to spontaneous
      deamination of 5-methylcytosine and cytosine, respectively. To elucidate the
      mechanisms that underlie sequence discrimination by MED1, we did single-turnover
      kinetics with the isolated, recombinant glycosylase domain of MED1.
      Quantification of MED1 substrate hierarchy confirmed MED1 preference for
      mismatches within a CpG context and showed preference for hemimethylated base
      mismatches. Furthermore, the k(st) values obtained with the uracil analogues 5
      fluorouracil and 5-iodouracil were over 20- to 30-fold higher than those obtained
      with uracil, indicating substantially higher affinity for halogenated bases. A 5
      iodouracil precursor is the halogenated nucleotide 5-iododeoxyuridine (5IdU), a
      cytotoxic and radiosensitizing agent. Cultures of mouse embryo fibroblasts (MEF)
      with different Med1 genotype derived from mice with targeted inactivation of the
      gene were evaluated for sensitivity to 5IdU. The results revealed that Med1-null
      MEFs are more sensitive to 5IdU than wild-type MEFs in both 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and colony formation
      assays. Furthermore, high-performance liquid chromatography analyses revealed
      that Med1-null cells exhibit increased levels of 5IdU in their DNA due to
      increased incorporation or reduced removal. These findings establish MED1 as a
      bona fide repair activity for the removal of halogenated bases and indicate that
      MED1 may play a significant role in 5IdU cytotoxicity.

PMID- 16885371
TI  - Oncolytic efficacy and enhanced safety of measles virus activated by tumor
      secreted matrix metalloproteinases.
AB  - Cancer cells secrete matrix metalloproteinases (MMP) that degrade the
      extracellular matrix and are responsible for some hallmarks of malignant cancer.
      Many viruses, including a few currently used in oncolytic virotherapy clinical
      trials, depend on intracellular proteases to process their proteins and activate
      their particles. We show here for measles virus (MV) that particle activation can
      be made dependent of proteases secreted by cancer cells. The MV depends on the
      intracellular protease furin to process and activate its envelope fusion (F)
      protein. To make F protein activation cancer cell specific, we introduced
      hexameric sequences recognized by an MMP and identified the mutant proteins most
      effective in fusing MMP-expressing human fibrosarcoma cells (HT1080). We showed
      that an MMP inhibitor interferes with syncytia formation elicited by mutant F
      proteins and confirmed MMP-dependent cleavage by Edman degradation sequence
      analysis. We generated recombinant MVs expressing the modified F proteins in
      place of furin-activated F. These viruses spread only in cells secreting MMP. In
      nude mice, an MMP-activated MV retarded HT1080 xenograft growth as efficiently as
      the furin-activated MV vaccine strain. In MV-susceptible mice, the furin
      activated virus caused lethal encephalitis upon intracerebral inoculation,
      whereas the MMP-activated did not. Thus, MV particle activation can be made
      dependent of proteases secreted by cancer cells, enhancing safety. This study
      opens the perspective of combining targeting at the particle activation, receptor
      recognition, and selective replication levels to improve the therapeutic index of
      MV and other viruses in ongoing clinical trials of oncolysis.

PMID- 16885372
TI  - Antagonism of CXCR3 inhibits lung metastasis in a murine model of metastatic
      breast cancer.
AB  - Tumor cells aberrantly express chemokines and/or chemokine receptors, and some
      may promote tumor growth and metastasis. We examined the expression and function
      of chemokine receptor CXCR3 in a syngeneic murine model of metastatic breast
      cancer. By flow cytometry, CXCR3 was detected in all murine mammary tumor cell
      lines examined. All human breast cancer cell lines examined also expressed CXCR3,
      as did the immortalized but nontumorigenic MCF-10A cell line. Interaction of
      CXCR3 ligands, CXCL9, CXCL10, and CXCL11, with CXCR3 on the highly malignant
      murine mammary tumor cell line 66.1 resulted in intracellular calcium
      mobilization and chemotaxis in vitro. To test the hypothesis that tumor
      metastasis is facilitated by CXCR3 expressed by tumor cells, we employed a small
      molecular weight antagonist of CXCR3, AMG487. 66.1 tumor cells were pretreated
      with AMG487 prior to i.v. injection into immune-competent female mice. Antagonism
      of CXCR3 on 66.1 tumor cells inhibited experimental lung metastasis, and this
      antimetastatic activity was compromised in mice depleted of natural killer cells.
      Systemic administration of AMG487 also inhibited experimental lung metastasis. In
      contrast to the antimetastatic effect of AMG487, local growth of 66.1 mammary
      tumors was not affected by receptor antagonism. These studies indicate that
      murine mammary tumor cells express CXCR3 which facilitates the development of
      lung metastases. These studies also indicate for the first time that a small
      molecular weight antagonist of CXCR3 has the potential to inhibit tumor
      metastasis.

PMID- 16885373
TI  - Responses of human colorectal tumor cells to treatment with the anti-epidermal
      growth factor receptor monoclonal antibody ICR62 used alone and in combination
      with the EGFR tyrosine kinase inhibitor gefitinib.
AB  - The anti-epidermal growth factor receptor (EGFR) monoclonal antibody cetuximab
      has been approved for the treatment of patients with metastatic colorectal
      cancer. However, there is currently no reliable marker for response to therapy
      with the EGFR inhibitors. In this study, we investigated the sensitivity of 10
      human colorectal tumor cell lines (DiFi, CCL218, CCL221, CCL225, CCL227, CCL228,
      CCL231, CCL235, CCL244, and HCT-116) to treatment with our anti-EGFR monoclonal
      antibody, ICR62, and/or the EGFR tyrosine kinase inhibitor, gefitinib. Of the
      cells examined, only DiFi contained high levels of constitutively active EGFR and
      were highly sensitive to treatment with both ICR62 (IC(50) = 0.52 nmol/L) and
      gefitinib (IC(50) = 27.5 nmol/L). In contrast, the growth of other tumor cell
      lines, which contained low levels of the EGFR, HER-2, and pAkt but comparable or
      even higher basal levels of phosphorylated mitogen-activated protein kinase
      (pMAPK), were relatively resistant to treatment with both inhibitors. Both ICR62
      and gefitinib induced EGFR down-regulation, reduced the basal levels of pEGFR at
      five known tyrosine residues, pMAPK, and pAkt, and increased the sub-G(1)
      population in DiFi cells. However, treatment with a combination of ICR62 and
      gefitinib neither sensitized colorectal tumor cells that were insensitive to
      treatment with the single agent nor enhanced the growth-inhibitory effect of the
      single agent in DiFi cells. These results indicate that basal levels of pMAPK and
      pAkt are not good indicators of response to the EGFR inhibitors in colorectal
      cancer cells and dual targeting of the EGFR by a combination of ICR62 and
      gefitinib is not superior to treatment with a single agent.

PMID- 16885374
TI  - Heparanase: a new metastasis-associated antigen recognized in breast cancer
      patients by spontaneously induced memory T lymphocytes.
AB  - Increased expression and secretion of heparanase (Hpa) by tumor cells promotes
      tumor invasion through extracellular matrices, tissue destruction, angiogenesis,
      and metastasis. Here, we show the existence in breast cancer patients of Hpa
      specific T lymphocytes by fluorescence-activated cell sorting flow cytometry
      using Hpa peptide-MHC class I tetramers. We furthermore show memory T-cell
      responses in a high proportion of breast cancer patients to Hpa-derived HLA-A2
      restricted peptides, leading to production of IFN-gamma and to generation of
      antitumor CTLs lysing breast cancer cells. Such CTLs recognized endogenously
      processed respective Hpa peptides on Hpa-transfected and Hpa-expressing
      untransfected breast carcinoma cells. According to these results and to the fact
      that such cells were not found in healthy people, Hpa seems to be an attractive
      new tumor-associated antigen and its HLA-A2-restricted peptides ought to be good
      candidates for peptide vaccination to reactivate memory immune responses to
      invasive and metastatic cancer cells.

PMID- 16885375
TI  - Selection of tumor-binding ligands in cancer patients with phage display
      libraries.
AB  - Phage display has been used extensively in vitro and in animal models to generate
      ligands and to identify cancer-relevant targets. We report here the use of phage
      display libraries in cancer patients to identify tumor-targeting ligands. Eight
      patients with stage IV cancer, including breast, melanoma, and pancreas, had
      phage-displayed random peptide or scFv library (1.6 x 10(8)-1 x 10(11)
      transducing units/kg) administered i.v.; tumors were excised after 30 minutes;
      and tumor-homing phage were recovered. In three patients, repeat panning was
      possible using phage recovered and amplified from that same patient's tumor. No
      serious side effects, including allergic reactions, were observed with up to
      three infusions. Patients developed antiphage antibodies that reached a
      submaximal level within the 10-day protocol window for serial phage
      administration. Tumor phage were recoverable from all the patients. Using a
      filter-based ELISA, several clones from a subset of the patients were identified
      that bound to a tumor from the same patient in which clones were recovered. The
      clone-binding to tumor was confirmed by immunostaining, bioassay, and real-time
      PCR-based methods. Binding studies with noncancer and cancer cell lines of the
      same histology showed specificity of the tumor-binding clones. Analysis of insert
      sequences of tumor-homing peptide clones showed several motifs, indicating
      nonrandom accumulation of clones in human tumors. This is the first reported
      series of cancer patients to receive phage library for serial panning of tumor
      targeting ligands. The lack of toxicity and the ability to recover clones with
      favorable characteristics are a first step for further research with this
      technology in cancer patients.

PMID- 16885376
TI  - Immunosurveillance of Erbb2 carcinogenesis in transgenic mice is concealed by a
      dominant regulatory T-cell self-tolerance.
AB  - To assess the role of CD4(+)CD25(+)Foxp3(+) regulatory T (Treg) cells in
      overcoming immunosurveillance of Erbb2 (HER-2/neu) mammary lesions, we studied
      the effects of their sustained removal in BALB/c female mice made transgenic for
      the rat Erbb2 (r-Erbb2) oncogene (BALB-neuT mice), which develop multiple mammary
      carcinomas. During the progression of these lesions, Treg cells expand in the
      spleen, tumor draining lymph nodes, and tumors. Repeated administration of anti
      CD25 antibodies extends tumor-free survival, reduces carcinoma multiplicity, and
      leads to the manifestation of a natural antibody and CTL-mediated reactivity
      against r-Erbb2. Loss of Foxp3(+) Treg cells during anti-CD25 treatment
      remarkably caused the disappearance of Gr1(+) immature myeloid cells, suggesting
      a cross-talk between these two inhibitory immune cell types. Treg cell expansion
      associated with r-Erbb2 overexpression may be seen as a physiologic response to
      dampen the immune reaction elicited by local anomalous overexpression of a self
      antigen.

PMID- 16885377
TI  - Inhibitory effects of B cells on antitumor immunity.
AB  - B-cell functions in antitumor immunity are not well understood. In this study, we
      evaluated the role of B cells in the development of antitumor immunity using
      Friend murine leukemia virus gag-expressing mouse EL-4 (EL-4 gag), D5 mouse
      melanoma, or MCA304 mouse sarcoma cells. To screen tumors for susceptibility to B
      cell-deficient immune environments, spleen cells from naive C57BL/6 [wild-type
      (WT)] and B-cell knockout (BKO) mice were cultured with irradiated tumor cells in
      vitro. When cells were stimulated with EL-4 gag or D5 (but not MCA304 tumors),
      IFN-gamma production from CD8 T cells and natural killer cells was markedly
      decreased in WT compared with BKO cultures. IFN-gamma production was correlated
      with CD40 ligand expression on the tumor and inversely with interleukin-10 (IL
      10) production by B cells. Sorted WT B cells produced more IL-10 than CD40
      knockout (CD40KO) B cells when cocultured with EL-4 gag or D5 (but not MCA304).
      IFN-gamma production by BKO cells was reduced by the addition of sorted naive WT
      B cells (partially by CD40KO B cells) or recombinant mouse IL-10. In vivo tumor
      progression mirrored in vitro studies in that WT mice were unable to control
      tumor growth whereas EL-4 gag and D5 tumors (but not MCA304) were eliminated in
      BKO mice. Robust in vivo antitumor CTLs developed only in BKO tumor-challenged
      mice. Our studies provide the first mechanistic basis for the concept that B-cell
      depletion could therapeutically enhance antitumor immune responses to certain
      tumors by decreasing IL-10 production from B cells.

PMID- 16885378
TI  - Vaccination strategy determines the emergence and dominance of CD8+ T-cell
      epitopes in a FVB/N rat HER-2/neu mouse model of breast cancer.
AB  - The HER-2/neu oncogene has >25 HLA epitopes, yet only one FVB/N mouse CD8(+) T
      cell epitope has been mapped to date. This epitope has been termed the
      immunodominant epitope for the FVB/N mouse, but we propose that the vaccination
      strategy determines the dominance of epitopes. Using a series of overlapping
      peptides, we have mapped another CD8(+) T-cell epitope that emerges in the FVB/N
      mouse following vaccination with Listeria monocytogenes-based vaccines that
      express fragments of HER-2/neu. Following the identification of this novel H
      2K(q)-restricted epitope, we sought to compare the T-cell response to this
      epitope with the previously identified PDSLRDLSVF epitope. This newly identified
      epitope and the previously identified epitope lie within fragments contained in
      different vaccines, the PDSLRDLSVF epitope in Lm-LLO-EC2 and the newly identified
      PYNYLSTEV epitope in Lm-LLO-EC1; thus, it has been possible to compare the
      responses of these epitopes independent of any competing response between the
      epitopes. CTL analysis of individual peptide-pulsed target cells and
      intracellular cytokine stain for IFN-gamma produced by splenocytes from Lm-LLO
      EC1 compared with Lm-LLO-EC2 vaccinated FVB/N mice shows that there is no
      difference between the responses generated to either of these epitopes. We also
      show that the avidity of the CD8(+) T cells for either of these epitopes is
      similar based on the concentration of peptide necessary to mediate similar levels
      of lysis of target cells. In addition, HER-2/neu DNA vaccination followed by CTL
      analysis further showed that both of these peptides can emerge as epitopes.

PMID- 16885379
TI  - Adenosine-mediated inhibition of the cytotoxic activity and cytokine production
      by activated natural killer cells.
AB  - Adenosine is an important signaling molecule that regulates multiple physiologic
      processes and exerts major anti-inflammatory actions. Tumors have high
      concentrations of adenosine, which could inhibit the function of tumor
      infiltrating lymphoid cells. We investigated the ability of adenosine and its
      stable analogue 2-chloroadenosine (CADO) to inhibit cytokine production and
      cytotoxic activity of lymphokine-activated killer (LAK) cells and determined
      whether both these effects are initiated via a common pathway. CADO strongly
      inhibited cytotoxic activity of LAK cells and attenuated the production of IFN
      gamma, granulocyte macrophage colony-stimulating factor, tumor necrosis factor
      alpha, and macrophage inflammatory protein-1alpha by LAK cells stimulated by
      cross-linking of the Ly49D receptor. These inhibitory effects were associated
      with the ability of CADO to stimulate cyclic AMP (cAMP) production and activate
      protein kinase A (PKA). Using cAMP analogues with different affinities for the A
      and B sites of the regulatory subunits of PKA types I and II, we found that
      activation of PKA I, but not PKA II, mimicked the inhibitory effects of CADO on
      LAK cell cytotoxic activity and cytokine production. Inhibitors of the PKA
      catalytic subunits (H89 and PKI(14-22) peptide) failed to abrogate the inhibitory
      effects of CADO whereas Rp-8-Br-cAMPS, an antagonist of the RI subunit, blocked
      the inhibitory effects of CADO. We conclude that the inhibitory effects of
      adenosine are probably mediated via cAMP-dependent activation of the RI subunits
      of PKA I but are independent of the catalytic activity of PKA. Tumor-produced
      adenosine could be a potent tumor microenvironmental factor inhibiting the
      functional activity of tumor-infiltrating immune cells.

PMID- 16885380
TI  - Tumor-derived matrix metalloproteinase-1 targets endothelial proteinase-activated
      receptor 1 promoting endothelial cell activation.
AB  - In the vascular system, circulating tumor cells interact with endothelial cells.
      Tumor-endothelial cross-talk transforms the intravascular milieu to a
      prothrombotic, proinflammatory, and cell-adhesive state called endothelial cell
      activation (ECA). In the present study, we analyze the potential of metastatic
      tumor-derived soluble factors to transform the vascular endothelium into a
      prothrombotic and proinflammatory activated state. Supernatant from cultured
      melanoma and colon cancer cells (A375, WM9, A7, and HT-29) induced an acute
      activation of macrovascular and microvascular endothelial cells (human umbilical
      vein endothelial cells and human dermal microvascular endothelial cells) as shown
      by intracellular calcium flux and secretion of von Willebrand factor and
      interleukin-8, all markers of acute ECA. This process was inhibited using
      specific proteinase-activated receptor 1 (PAR1) inhibitors (RWJ-58259 and SCH
      79797), indicating a mediating role for endothelial thrombin receptors.
      Immunofluorescence, Western blot analysis, and collagenase activity assay of
      tumor cells and culture supernatant revealed the presence of matrix
      metalloproteinase-1 (MMP-1), a recently described activator of PAR1. Inhibition
      of MMP-1 in supernatant from cultured tumor cells significantly attenuated ECA.
      Additional studies using isolated human MMP-1 (5 nmol/L) proved the presence of a
      functional MMP-1/PAR1 axis in tumor-endothelial communication. These findings
      show a new pathway of tumor-endothelial cross-talk via an intravascular MMP1/PAR1
      axis in microvascular and macrovascular endothelium. Inhibition of this cross
      talk may be a powerful means to prevent tumor-induced ECA and thus thrombotic and
      inflammatory cell adhesion.

PMID- 16885381
TI  - Role of androgens on MCF-7 breast cancer cell growth and on the inhibitory effect
      of letrozole.
AB  - Previous work has shown that androgens inhibit breast cancer cells and tumor
      growth. On the other hand, androgens can be converted to mitogenic estrogens by
      aromatase in breast cancer cells. Here, we report that androgens, such as the
      aromatizable androstenedione and the non-aromatizable 5alpha-dihydrotestosterone,
      inhibit MCF-7 cell proliferation. This effect is observed only in the absence or
      at a low concentration of estrogens and is evident in cells with low aromatase
      activity. Growth of a new aromatase stably transfected MCF-7 cell line (Ac1) was
      stimulated by conversion of androstenedione into estrogens and was sensitive to
      aromatase inhibitors. We show that blockade of the androgen receptor (AR) in
      these cells by the antiandrogen casodex or by the anti-AR small interfering RNA
      inhibited the antiproliferative effect of dihydrotestosterone and letrozole
      (aromatase inhibitor). We also show that suppression of the estrogen-induced
      antiapoptotic protein Bcl-2 may be involved in the antiproliferative effects of
      androgens and letrozole. These effects can be reversed by casodex. In conclusion,
      the results suggest that aromatase inhibitors may exert their antiproliferative
      effect not only by reducing the intracellular production of estrogens but also by
      unmasking the inhibitory effect of androgens acting via the AR.

PMID- 16885382
TI  - Androgens induce prostate cancer cell proliferation through mammalian target of
      rapamycin activation and post-transcriptional increases in cyclin D proteins.
AB  - Androgen receptor (AR) plays a central role in prostate cancer, with most tumors
      responding to androgen deprivation therapies, but the molecular basis for this
      androgen dependence has not been determined. Androgen [5alpha-dihydrotestosterone
      (DHT)] stimulation of LNCaP prostate cancer cells, which have constitutive
      phosphatidylinositol 3-kinase (PI3K)/Akt pathway activation due to PTEN loss,
      caused increased expression of cyclin D1, D2, and D3 proteins, retinoblastoma
      protein hyperphosphorylation, and cell cycle progression. However, cyclin D1 and
      D2 message levels were unchanged, indicating that the increases in cyclin D
      proteins were mediated by a post-transcriptional mechanism. This mechanism was
      identified as mammalian target of rapamycin (mTOR) activation. DHT treatment
      increased mTOR activity as assessed by phosphorylation of the downstream targets
      p70 S6 kinase and 4E-BP1, and mTOR inhibition with rapamycin blocked the DHT
      stimulated increase in cyclin D proteins. Significantly, DHT stimulation of mTOR
      was not mediated through activation of the PI3K/Akt or mitogen-activated protein
      kinase/p90 ribosomal S6 kinase pathways and subsequent tuberous sclerosis complex
      2/tuberin inactivation or by suppression of AMP-activated protein kinase. In
      contrast, mTOR activation by DHT was dependent on AR-stimulated mRNA synthesis.
      Oligonucleotide microarrays showed that DHT-stimulated rapid increases in
      multiple genes that regulate nutrient availability, including transporters for
      amino acids and other organic ions. These results indicate that a critical
      function of AR in PTEN-deficient prostate cancer cells is to support the
      pathologic activation of mTOR, possibly by increasing the expression of proteins
      that enhance nutrient availability and thereby prevent feedback inhibition of
      mTOR.

PMID- 16885383
TI  - Genetic bases of estrogen-induced tumorigenesis in the rat: mapping of loci
      controlling susceptibility to mammary cancer in a Brown Norway x ACI intercross.
AB  - Exposure to estrogens is associated with an increased risk of breast cancer. Our
      laboratory has shown that the ACI rat is uniquely susceptible to 17beta-estradiol
      (E2)-induced mammary cancer. We previously mapped two loci, Emca1 and Emca2
      (estrogen-induced mammary cancer), that act independently to determine
      susceptibility to E2-induced mammary cancer in crosses between the susceptible
      ACI rat strain and the genetically related, but resistant, Copenhagen (COP) rat
      strain. In this study, we evaluate susceptibility to E2-induced mammary cancer in
      a cross between the ACI strain and the unrelated Brown Norway (BN) rat strain.
      Whereas nearly 100% of the ACI rats developed mammary cancer when treated
      continuously with E2, BN rats did not develop palpable mammary cancer during the
      196-day course of E2 treatment. Susceptibility to E2-induced mammary cancer
      segregated as a dominant or incompletely dominant trait in a cross between BN
      females and ACI males. In a population of 251 female (BN x ACI)F(2) rats, we
      observed evidence for a total of five genetic determinants of susceptibility. Two
      loci, Emca4 and Emca5, were identified when mammary cancer status at sacrifice
      was evaluated as the phenotype, and three additional loci, Emca6, Emca7, and
      Emca8, were identified when mammary cancer number was evaluated as the phenotype.
      A total of three genetic interactions were identified. These data indicate that
      susceptibility to E2-induced mammary cancer in the BN x ACI cross behaves as a
      complex trait controlled by at least five loci and multiple gene-gene
      interactions.

PMID- 16885384
TI  - c-Abl expression in chronic lymphocytic leukemia cells: clinical and therapeutic
      implications.
AB  - c-Abl is important for normal B-cell development, but little is known about the
      function of this nonreceptor tyrosine kinase in chronic lymphocytic leukemia
      (CLL). Therefore, the aim of the present study was to examine the clinical,
      therapeutic, and pathogenetic importance of c-Abl in this disease. We show that
      the malignant cells of CLL predominantly express the type 1b splice variant of c
      Abl and that the expression of c-Abl protein is higher in CLL cells than in
      normal peripheral blood B cells. Moreover, we show that the levels of c-Abl
      protein expression correlate positively with tumor burden and disease stage, and
      negatively with IgV(H) mutation. We also show that STI-571, an inhibitor of c-Abl
      kinase activity, induces apoptosis of CLL cells with high c-Abl expression levels
      through a mechanism involving inhibition of nuclear factor kappaB. We conclude
      that overexpression of c-Abl is likely to play a pathogenetic role in CLL and
      that STI-571 may be of potential use in the treatment of this disease.

PMID- 16885386
TI  - 15-hydroxyprostaglandin dehydrogenase is a tumor suppressor of human breast
      cancer.
AB  - Prostaglandin E(2) plays a growth-stimulatory role in breast cancer, and the rate
      limiting enzyme in its synthesis, cyclooxygenase-2, is often overexpressed in
      these cancers. Little is known about the role of the key prostaglandin catabolic
      enzyme 15-hydroxyprostaglandin dehydrogenase (15-PGDH) in breast cancer
      pathogenesis. Using a pharmacologically based screen for epigenetically silenced
      genes, we found low levels of 15-PGDH in MDA-MB-231 cells [estrogen receptor (ER)
      negative] but high levels in MCF-7 cells (ER positive) and observed its up
      regulation following demethylation treatment. Further analysis revealed
      methylation of the 15-PGDH promoter in one breast cancer cell line and 30% of
      primary tumors. Analysis of 15-PGDH expression revealed low levels in 40% of
      primary breast tumors and identified a correlation between 15-PGDH and ER
      expression. Transfection assays showed that transient up-regulation of 15-PGDH
      levels in MDA-MB-231 cells resulted in a decreased clonal growth, and stable up
      regulation significantly decreased the ability of these cells to form tumors in
      athymic mice. In contrast, transient silencing of 15-PGDH in MCF-7 cells resulted
      in their enhanced proliferation, and a stable silencing in these cells enhanced
      cell cycle entry in vitro and tumorigenicity in vivo. Forced expression of 15
      PGDH inhibited the ER pathway and silencing of 15-PGDH up-regulated expression of
      aromatase. In addition, 15-PGDH levels were down-regulated by estrogen but up
      regulated by the tumor suppressor gene CAAT/enhancer binding protein alpha. Our
      results indicate for the first time that 15-PGDH may be a novel tumor suppressor
      gene in breast cancer, and suggest that this enzyme can modulate the ER pathway.

PMID- 16885385
TI  - Screening for Lynch syndrome (hereditary nonpolyposis colorectal cancer) among
      endometrial cancer patients.
AB  - Endometrial cancer is the most common cancer in women with Lynch syndrome. The
      identification of individuals with Lynch syndrome is desirable because they can
      benefit from increased cancer surveillance. The purpose of this study was to
      determine the feasibility and desirability of molecular screening for Lynch
      syndrome in all endometrial cancer patients. Unselected endometrial cancer
      patients (N = 543) were studied. All tumors underwent microsatellite instability
      (MSI) testing. Patients with MSI-positive tumors underwent testing for germ line
      mutations in MLH1, MSH2, MSH6, and PMS2. Of 543 tumors studied, 118 (21.7%) were
      MSI positive (98 of 118 MSI high and 20 of 118 MSI low). All 118 patients with
      MSI-positive tumors had mutation testing, and nine of them had deleterious germ
      line mutations (one MLH1, three MSH2, and five MSH6). In addition, one case with
      an MSI-negative tumor had abnormal MSH6 immunohistochemical staining and was
      subsequently found to have a mutation in MSH6. Immunohistochemical staining was
      consistent with the mutation result in all seven truncating mutation-positive
      cases but was not consistent in two of the three missense mutation cases. We
      conclude that in central Ohio, at least 1.8% (95% confidence interval, 0.9-3.5%)
      of newly diagnosed endometrial cancer patients had Lynch syndrome. Seven of the
      10 Lynch syndrome patients did not meet any published criteria for hereditary
      nonpolyposis colorectal cancer, and six of them were diagnosed at age >50.
      Studying all endometrial cancer patients for Lynch syndrome using a combination
      of MSI and immunohistochemistry for molecular prescreening followed by gene
      sequencing and deletion analysis is feasible and may be desirable.

PMID- 16885387
TI  - Ifosfamide-induced nephrotoxicity: mechanism and prevention.
AB  - The efficacy of ifosfamide (IFO), an antineoplastic drug, is severely limited by
      a high incidence of nephrotoxicity of unknown etiology. We hypothesized that
      inhibition of complex I (C-I) by chloroacetaldehyde (CAA), a metabolite of IFO,
      is the chief cause of nephrotoxicity, and that agmatine (AGM), which we found to
      augment mitochondrial oxidative phosphorylation and beta-oxidation, would prevent
      nephrotoxicity. Our model system was isolated mitochondria obtained from the
      kidney cortex of rats treated with IFO or IFO + AGM. Oxidative phosphorylation
      was determined with electron donors specific to complexes I, II, III, or IV (C-I,
      C-II, C-III, or C-IV, respectively). A parallel study was done with (13)C-labeled
      pyruvate to assess metabolic dysfunction. Ifosfamide treatment significantly
      inhibited oxidative phosphorylation with only C-I substrates. Inhibition of C-I
      was associated with a significant elevation of [NADH], depletion of [NAD], and
      decreased flux through pyruvate dehydrogenase and the TCA cycle. However,
      administration of AGM with IFO increased [cyclic AMP (cAMP)] and prevented IFO
      induced inhibition of C-I. In vitro studies with various metabolites of IFO
      showed that only CAA inhibited C-I, even with supplementation with 2
      mercaptoethane sulfonic acid. Following IFO treatment daily for 5 days with 50
      mg/kg, the level of CAA in the renal cortex was approximately 15 micromol/L.
      Taken together, these observations support the hypothesis that CAA is accumulated
      in renal cortex and is responsible for nephrotoxicity. AGM may be protective by
      increasing tissue [cAMP], which phosphorylates NADH:oxidoreductase. The current
      findings may have an important implication for the prevention of IFO-induced
      nephrotoxicity and/or mitochondrial diseases secondary to defective C-I.

PMID- 16885388
TI  - Cognitive and motor development of 8-year-old children born after ICSI compared
      to spontaneously conceived children.
AB  - BACKGROUND: As a continuation of two large-scale, multicentre studies on the
      development of 5-year-old ICSI children, we present results of the follow-up
      study undertaken on the cognitive and motor development of 8-year-old ICSI
      children. METHODS: Developmental outcomes of 151 8-year-old singletons born
      through ICSI after 32 weeks of gestation were compared with those of 153
      singletons of the same age born after spontaneous conception (SC). Part of this
      population was seen in a cohort at the age 5 years. Outcome measures include
      Wechsler Intelligence Scale for Children-Revised (WISC-R) and Movement Assessment
      Battery for Children (ABC). RESULTS: Regarding intellectual functioning, ICSI
      children tend to obtain significantly higher total (P < 0.01), verbal (P < 0.01)
      and performance (P < 0.05) intelligence scores than SC children, nevertheless
      remaining in similar ranges. These effects are small (Cohen's d < 0.50). High
      maternal educational level stayed in the regression as a factor accounting for
      some of the variance in total IQ between the groups. In terms of motor
      development, no significant differences were found between ICSI and SC children
      regarding overall motor skills, manual, balance and ball skills. CONCLUSION: In
      this follow-up study, ICSI and SC children show a comparable cognitive and motor
      development until the age of 8 years.

PMID- 16885389
TI  - Autonomy versus protection--who benefits from the regulation of IVF?
AB  - Parliament will soon be asked to decide about the future regulation of IVF in the
      United Kingdom. Given that IVF is now considered to be a routine clinical
      procedure and the fact that we live in an age of unprecedented emphasis on
      autonomy and patient rights, the justification for continuing to regulate this
      form of treatment will undoubtedly be challenged. This article considers the four
      key reasons why the Human Fertilisation and Embryology Authority (HFEA) was
      originally established-to protect patients and their children, to allay public
      concerns, to protect scientific freedom and to protect IVF practitioners from
      claims of unethical behaviour-and asks to what extent these reasons are still
      valid today. Acknowledging that there are difficulties and frustrations with the
      HFEA, the article warns that all parties-patients, researchers, IVF practitioners
      and society-have a lot to lose by limiting the scope of regulation. It concludes
      that before moving too quickly to get rid of the HFEA as we know it, we need to
      think carefully about whether the burdens and restrictions imposed by regulation
      are sufficiently onerous to justify this loss.

PMID- 16885390
TI  - Mechanically stimulated osteocytes regulate osteoblastic activity via gap
      junctions.
AB  - The strong correlation between a bone's architectural properties and the
      mechanical forces that it experiences has long been attributed to the existence
      of a cell that not only detects mechanical load but also structurally adapts the
      bone matrix to counter it. One of the most likely cellular candidates for such a
      "mechanostat" is the osteocyte, which resides within the mineralized bone matrix
      and is perfectly situated to detect mechanically induced signals. However, as
      osteocytes can neither form nor resorb bone, it has been hypothesized that they
      orchestrate mechanically induced bone remodeling by coordinating the actions of
      cells residing on the bone surface, such as osteoblasts. To investigate this
      hypothesis, we developed a novel osteocyte-osteoblast coculture model that mimics
      in vivo systems by permitting us to expose osteocytes to physiological levels of
      fluid shear while shielding osteoblasts from it. Our results show that osteocytes
      exposed to a fluid shear rate of 4.4 dyn/cm(2) rapidly increase the alkaline
      phosphatase activity of the shielded osteoblasts and that osteocytic-osteoblastic
      physical contact is a prerequisite. Furthermore, both functional gap junctional
      intercellular communication and the mitogen-activated protein kinase,
      extracellular signal-regulated kinase 1/2 signaling pathway are essential
      components in the osteoblastic response to osteocyte communicated mechanical
      signals. By utilizing other nonosteocytic coculture models, we also show that the
      ability to mediate osteoblastic alkaline phosphatase levels in response to the
      application of fluid shear is a phenomena unique to osteocytes and is not
      reproduced by other mesenchymal cell types.

PMID- 16885391
TI  - Apical electrolyte concentration modulates barrier function and tight junction
      protein localization in bovine mammary epithelium.
AB  - In vitro mammary epithelial cell models typically fail to form a consistently
      tight barrier that can effectively separate blood from milk. Our hypothesis was
      that mammary epithelial barrier function would be affected by changes in luminal
      ion concentration and inflammatory cytokines. Bovine mammary epithelial (BME-UV
      cell line) cells were grown to confluence on permeable supports with a standard
      basolateral medium and either high-electrolyte (H-elec) or low-electrolyte (L
      elec) apical medium for 14 days. Apical media were changed to/from H-elec medium
      at predetermined times prior to assay. Transepithelial electrical resistance
      (R(te)) was highest in monolayers continuously exposed to apical L-elec. A time
      dependent decline in R(te) began within 24 h of H-elec medium exposure. Change
      from H-elec medium to L-elec medium time-dependently increased R(te). Permeation
      by FITC-conjugated dextran was elevated across monolayers exposed to H-elec,
      suggesting compromise of a paracellular pathway. Significant alteration in
      occludin distribution was evident, concomitant with the changes in R(te),
      although total occludin was unchanged. Neither substitution of Na(+) with N
      methyl-d-glucosamine (NMDG(+)) nor pharmacological inhibition of transcellular
      Na(+) transport pathways abrogated the effects of apical H-elec medium on R(te).
      Tumor necrosis factor alpha, but not interleukin-1beta nor interleukin-6, in the
      apical compartment caused a significant decrease in R(te) within 8 h. These
      results indicate that mammary epithelium is a dynamic barrier whose cell-cell
      contacts are acutely modulated by cytokines and luminal electrolyte environment.
      Results not only demonstrate that BME-UV cells are a model system representative
      of mammary epithelium but also provide critical information that can be applied
      to other mammary model systems to improve their physiological relevance.

PMID- 16885392
TI  - Effects of estradiol on phenylephrine contractility associated with intracellular
      calcium release in rat aorta.
AB  - The ability of estradiol to affect phenylephrine-induced contraction and the
      subsequent increase in resting tone, associated with capacitative Ca(2+) entry
      across the plasma membrane, was evaluated in rat aortic rings incubated in Ca(2+)
      free solution. The incubation with estradiol (1-100 nM, 5 min) inhibited both the
      phenylephrine-induced contraction and the IRT. Neither cycloheximide (1 microM;
      inhibitor of protein synthesis) nor tamoxifen (1 microM; blocker of estrogenic
      receptors) modified the effects of estradiol. Estradiol (100 microM) also blocked
      the contractile response to serotonin (10 microM) but not to caffeine (10 mM). In
      addition, estradiol (100 microM) inhibited the contractile responses to
      cyclopiazonic acid (1 microM; selective Ca(2+)-ATPase inhibitor) associated with
      capacitative Ca(2+) influx through non-L-type Ca(2+) channels. Finally, estradiol
      inhibited the Ca(2+)-induced increases in intracellular free Ca(2+) (after
      pretreatment with phenylephrine) in cultured rat aorta smooth muscle cells
      incubated in Ca(2+)-free solution. In conclusion, estradiol interfered in a
      concentration-dependent manner with Ca(2+)-dependent contractile effects mediated
      by the stimuli of alpha(1)-adrenergic and serotonergic receptors and inhibited
      the capacitative Ca(2+) influx through both L-type and non-L-type Ca(2+)
      channels. Such effects are in essence nongenomic and not mediated by the
      intracellular estrogenic receptor.

PMID- 16885393
TI  - Regulation of myostatin expression and myoblast differentiation by FoxO and SMAD
      transcription factors.
AB  - Myostatin, a member of the transforming growth factor (TGF)-beta family, plays an
      important role in regulating skeletal muscle growth and differentiation. Here we
      examined the role of FoxO1 and SMAD transcription factors in regulating myostatin
      gene expression and myoblast differentiation in C(2)C(12) myotubes in vitro. Both
      myostatin and FoxO1 mRNA expression were greater in fast- vs. slow-twitch
      skeletal muscles in vivo. Moreover, expression of a constitutively active form of
      FoxO1 increased myostatin mRNA and increased activity of a myostatin promoter
      reporter construct in differentiated C(2)C(12) myotubes. Mutagenesis of highly
      conserved FoxO or SMAD binding sites significantly decreased myostatin promoter
      activity, and binding assays showed that both FoxO1 and SMADs bind to their
      respective sites in the myostatin promoter. Treatment with TGF-beta and/or
      overexpression of SMAD2, -3, or -4 also resulted in a significant increase in
      myostatin promoter activity. Treatment with TGF-beta along with overexpression of
      SMAD2 and FoxO1 resulted in the largest increase in myostatin promoter activity.
      Finally, TGF-beta treatment and SMAD2 overexpression greatly potentiated FoxO1
      mediated suppression of myoblast differentiation. Together these data demonstrate
      that FoxO1 and SMAD transcription factors regulate the expression of myostatin
      and contribute to the control of muscle cell growth and differentiation.

PMID- 16885394
TI  - Nitric oxide regulation of mitochondrial oxygen consumption I: cellular
      physiology.
AB  - Mitochondrial biochemistry is complex, expanding from oxygen consumption,
      oxidative phosphorylation, lipid catabolism, heme biosynthesis, to apoptosis,
      calcium homeostasis, and production of reactive oxygen species, including nitric
      oxide (NO). The latter molecule is produced by a mitochondrial NO synthase
      (mtNOS). The rates of consumption and production determine the steady-state
      concentration of NO at subcellular levels, leading to regulation of mitochondrial
      events. Temporospatial processes tightly regulate production of NO in
      mitochondria to maximize target effects and minimize deleterious reactions.
      Temporal regulatory mechanisms of mtNOS include activation by calcium signaling
      and transcriptional/translational regulations. Calcium-activated mtNOS inhibits
      mitochondrial respiration, resulting in a decrease of the oxygen consumption.
      This negative regulation antagonizes the effects of calcium on calcium-dependent
      dehydrogenases in the citric acid cycle, preventing the formation of anoxic foci.
      Temporal regulation of NO production by intracellular calcium signaling is a
      complex process, considering the heterogeneous intracellular calcium response and
      distribution. NO production in mitochondria is spatially regulated by mechanisms
      that determine subcellular localization of mtNOS, likely acylation and protein
      protein interactions, in addition to transcriptional regulation as neuronal NOS.
      Because NO rapidly decays in mitochondria, subcellular localization of mtNOS is
      crucial for NO to function as a signal molecule. These temporospatial processes
      are biologically important to allow NO to act as an effective signal molecule to
      regulate mitochondrial events such as oxygen consumption and reactive oxygen
      species production.

PMID- 16885395
TI  - Mitochondrial transport in processes of cortical neurons is independent of
      intracellular calcium.
AB  - Mitochondria show extensive movement along neuronal processes, but the mechanisms
      and function of this movement are not clearly understood. We have used high
      resolution confocal microscopy to simultaneously monitor movement of mitochondria
      and changes in intracellular [Ca(2+)] ([Ca(2+)](i)) in rat cortical neurons. A
      significant percentage (27%) of the total mitochondria in cortical neuronal
      processes showed movement over distances of >2 microM. The average velocity was
      0.52 microm/s. The velocity, direction, and pattern of mitochondrial movement
      were not affected by transient increases in [Ca(2+)](i) associated with
      spontaneous firing of action potentials. Stimulation of Ca(2+) transients with
      forskolin (10 microM) or bicuculline (10 microM), or sustained elevations of
      [Ca(2+)](i) evoked by glutamate (10 microM) also had no effect on mitochondrial
      transit. Neither removal of extracellular Ca(2+), depletion of intracellular
      Ca(2+) stores with thapsigargin, or inhibition of synaptic activity with TTX (1
      microM) or a cocktail of CNQX (10 microM) and MK801 (10 microM) affected
      mitochondrial movement. These results indicate that movement of mitochondria
      along processes is a fundamental activity in neurons that occurs independently of
      physiological changes in [Ca(2+)](i) associated with action potential firing,
      synaptic activity, or release of Ca(2+) from intracellular stores.

PMID- 16885396
TI  - Statin-induced apoptosis and skeletal myopathy.
AB  - Over 100 million prescriptions were filled for statins (3-hydroxy-3
      methylglutaryl coenzyme A reductase inhibitors) in 2004. Statins were originally
      developed to lower plasma cholesterol in patients with hypercholesterolemia and
      are the most effective drugs on the market in doing so. Because of the discovered
      pleiotropic effects of statins, the use has expanded to the treatment of many
      other conditions, including ventricular arrythmias, idiopathic dilated
      cardiomyopathy, cancer, osteoporosis, and diabetes. The elderly population is
      growing. Therefore, it is estimated that the number of statin users will also
      increase. Fortunately, the use of statins is relatively safe with few side
      effects. Myopathy is the most common side effect with symptoms ranging from
      fatigue, weakness, and pain to symptoms associated with rhabdomyolysis which is a
      life-threatening condition. The development of statin-induced rhabdomyolysis is
      rare occurring in approximately 0.1% of patients; however, the occurrence of less
      severe symptoms is underreported and may be 1-5% or more. Physical exercise
      appears to increase the likelihood for the development of myopathy in patients
      taking statins. It is thought that as many as 25% of statin users who exercise
      may experience muscle fatigue, weakness, aches, and cramping due to statin
      therapy and potentially dismissed by the patient and physician. The mechanisms
      causing statin-induced myopathy have not been elucidated; however, research
      efforts suggest that apoptosis of myofibers may contribute. The mitochondrion is
      considered a regulatory center of apoptosis, and therefore its role in the
      induction of apoptosis will be discussed as well as the mechanism of statin
      induced apoptosis and myopathy.

PMID- 16885397
TI  - Building the power house: recent advances in mitochondrial studies through
      proteomics and systems biology.
AB  - The emerging field of systems biology seeks to develop novel approaches to
      integrate heterogeneous data sources for effective analysis of complex living
      systems. Systemic studies of mitochondria have generated a large number of
      proteomic data sets in numerous species, including yeast, plant, mouse, rat, and
      human. Beyond component identification, mitochondrial proteomics is recognized as
      a powerful tool for diagnosing and characterizing complex diseases associated
      with these organelles. Various proteomic techniques for isolation and
      purification of proteins have been developed; each tailored to preserve protein
      properties relevant to study of a particular disease type. Examples of such
      techniques include immunocapture, which minimizes loss of posttranslational
      modification, 4-iodobutyltriphenylphosphonium labeling, which quantifies protein
      redox states, and surface-enhanced laser desorption ionization-time-of-flight
      mass spectrometry, which allows sequence-specific binding. With the rapidly
      increasing number of discovered molecular components, computational models are
      also being developed to facilitate the organization and analysis of such data.
      Computational models of mitochondria have been accomplished with top-down and
      bottom-up approaches and have been steadily improved in size and scope. Results
      from top-down methods tend to be more qualitative but are unbiased by prior
      knowledge about the system. Bottom-up methods often require the incorporation of
      a large amount of existing data but provide more rigorous and quantitative
      information, which can be used as hypotheses for subsequent experimental studies.
      Successes and limitations of the studies reviewed here provide opportunities and
      challenges that must be addressed to facilitate the application of systems
      biology to larger systems.

PMID- 16885398
TI  - Inhibition of Galphaq-dependent PLC-beta1 activity by PKG and PKA is mediated by
      phosphorylation of RGS4 and GRK2.
AB  - In smooth muscle of the gut, G(q)-coupled receptor agonists activate
      preferentially PLC-beta1 to stimulate phosphoinositide (PI) hydrolysis and
      inositol 1,4,5-trisphosphate (IP(3)) generation and induce IP(3)-dependent Ca(2+)
      release. Inhibition of Ca(2+) mobilization by cAMP- (PKA) and cGMP-dependent
      (PKG) protein kinases reflects inhibition of PI hydrolysis by both kinases and
      PKG-specific inhibitory phosphorylation of IP(3) receptor type I. The mechanism
      of inhibition of PLC-beta1-dependent PI hydrolysis has not been established.
      Neither G(q) nor PLC-beta1 was directly phosphorylated by PKA or PKG in gastric
      smooth muscle cells. However, both kinases 1) phosphorylated regulator of G
      protein signaling 4 (RGS4) and induced its translocation from cytosol to plasma
      membrane, 2) enhanced ACh-stimulated association of RGS4 and Galpha(q).GTP and
      intrinsic Galpha(q).GTPase activity, and 3) inhibited ACh-stimulated PI
      hydrolysis. RGS4 phosphorylation and inhibition of PI hydrolysis were blocked by
      selective PKA and PKG inhibitors. Expression of RGS4(S52A), which lacks a PKA/PKG
      phosphorylation site, blocked the increase in GTPase activity and the decrease in
      PI hydrolysis induced by PKA and PKG. Blockade of PKA-dependent effects was only
      partial. Selective phosphorylation of G protein-coupled receptor kinase 2 (GRK2),
      which contains a RGS domain, by PKA augmented ACh-stimulated GRK2:Galpha(q).GTP
      association; both effects were blocked in cells expressing GRK2(S685A), which
      lacks a PKA phosphorylation site. Inhibition of PI hydrolysis induced by PKA was
      partly blocked in cells expressing GRK2(S685A) and completely blocked in cells
      coexpressing GRK2(S685A) and RGS4(S52A) or Galpha(q)(G188S), a Galpha(q) mutant
      that binds GRK2 but not RGS4. The results demonstrate that inhibition of PLC
      beta1-dependent PI hydrolysis by PKA is mediated via stimulatory phosphorylation
      of RGS4 and GRK2, leading to rapid inactivation of Galpha(q).GTP. PKG acts only
      via phosphorylation of RGS4.

PMID- 16885399
TI  - Electrocardiogram differentiation of benign early repolarization versus acute
      myocardial infarction by emergency physicians and cardiologists.
AB  - OBJECTIVES: ST-segment elevation (STE) related to benign early repolarization
      (BER), a common normal variant, can be difficult to distinguish from acute
      myocardial infarction (AMI). The authors compared the electrocardiogram (ECG)
      interpretations of these two entities by emergency physicians (EPs) and
      cardiologists. METHODS: Twenty-five cases (13 BER, 12 AMI) of patients presenting
      to the emergency department with chest pain were identified. Criteria for BER
      required four of the following: 1) widespread STE (precordial greater than limb
      leads), 2) J-point elevation, 3) concavity of initial up-sloping portion of ST
      segment, 4) notching or irregular contour of J point, and 5) prominent,
      concordant T waves. Additional BER criteria were 1) stable ECG pattern, 2)
      negative cardiac injury markers, and 3) normal cardiac stress test or
      angiography. AMI criteria were 1) regional STE, 2) positive cardiac injury
      markers, and 3) identification of culprit coronary artery by angiography in less
      than eight hours of presentation. The 25 ECGs were distributed to 12 EPs and 12
      cardiologists (four in academic medicine, four in community practice, and four in
      community academics [health maintenance organization] in each physician group).
      The physicians were informed of the patients' age, gender, and race, and they
      then interpreted the ECGs as BER or AMI. Undercalls (AMI misdiagnosed as BER) and
      overcalls (BER misdiagnosed as AMI) were calculated for each physician group.
      RESULTS: Cardiologists correctly interpreted 90% of ECGs, and EPs correctly
      interpreted 81% of ECGs. The proportion of undercalls (missed AMI/total AMI) was
      2.8% for cardiologists (95% confidence interval [CI] = 0.09% to 5.5%) compared
      with 9.7% for EPs (95% CI = 4.8% to 14.6%) (p = 0.02). The proportion of
      overcalls (missed BER/total BER) was 17.3% for cardiologists (95% CI = 11.4% to
      23.3%) versus 27.6% for EPs (95% CI = 20.6% to 34.6%) (p = 0.03). The mean number
      of years in practice was 19.8 for cardiologists (95% CI = 19 to 20.5) and 11
      years for EPs (95% CI = 10.5 to 12.0) (p < 0.001). CONCLUSIONS: Although correct
      interpretation was high in both groups, cardiologists, who had significantly more
      years of practice, had fewer misinterpretations than EPs in distinguishing BER
      from AMI electrocardiographically.

PMID- 16885400
TI  - Hospital disaster preparedness in Los Angeles County.
AB  - BACKGROUND: There are no standardized measures of hospital disaster preparedness
      or hospital "surge capacity." OBJECTIVES: To characterize disaster preparedness
      among a cohort of hospitals in Los Angeles County, focusing on practice
      variation, plan characteristics, and surge capacity. METHODS: This was a
      descriptive, cross-sectional survey study, followed by on-site verification.
      Forty-five 9-1-1 receiving hospitals in Los Angeles County, CA, participated.
      Evaluations of hospital disaster plan structure, vendor agreements, modes of
      communication, medical and surgical supplies, involvement of law enforcement,
      mutual aid agreements with other facilities, drills and training, surge capacity
      (assessed by monthly emergency department diversion status, available beds,
      ventilators, and isolation rooms), decontamination capability, and pharmaceutical
      stockpiles were assessed by survey. RESULTS: Forty-three of 45 hospital plans
      (96%) were based on the Hospital Emergency Incident Command System, and the
      majority had protocols for hospital lockdown (100%), canceling elective surgeries
      (93%), early discharge (98%), day care for children of staff (88%), designating
      victim overflow areas (96%), and predisaster "preferred" vendor agreements (96%).
      All had emergency medical services-compatible radios and more than three days'
      worth of supplies. Fewer hospitals involved law enforcement (56%) or had mutual
      aid agreements with other hospitals (20%) or long-term care facilities (7%).
      Although the vast majority (96%) conducted multiagency drills, only 16% actually
      involved other agencies in their disaster training. Only 13 of 45 hospitals (29%)
      had a surge capacity of greater than 20 beds. Less than half (42%) had ten or
      more isolation rooms, and 27 hospitals (60%) were on diversion greater than 20%
      of the time. Thirteen hospitals (29%) had immediate access to six or more
      ventilators. Less than half had warm-water decontamination (42%), while
      approximately one half (51%) had a chemical antidote stockpile and 42% had an
      antibiotic stockpile. CONCLUSIONS: Among hospitals in Los Angeles County,
      disaster preparedness and surge capacity appear to be limited by a failure to
      fully integrate interagency training and planning and a severely limited surge
      capacity, although there is a generally high level of availability of equipment
      and supplies.

PMID- 16885401
TI  - Characteristics of medical surge capacity demand for sudden-impact disasters.
AB  - OBJECTIVES: To describe the characteristics of the demand for medical care during
      sudden-impact disasters, focusing on local U.S. communities and the initial
      phases of sudden-impact disasters. METHODS: Established databases and published
      reports were used as data sources. Data were obtained to describe the baseline
      capacity of the U.S. medical system. Information for the initial phases of a
      sudden-impact disaster was sought to allow for characterization of the length of
      time before a U.S. community can expect arrival of outside assistance, the
      expected types of medical surge demands, the expected time for the peak in
      medical-care demand, and the expected health system access points. RESULTS: The
      earliest that outside assistance arrived for a community subject to a sudden
      impact disaster was 24 hours, with a range from 24 to 96 hours. After sudden
      impact disasters, 84% to 90% of health care demand was for conditions that were
      managed on an ambulatory basis. Emergency departments (EDs) were the access point
      for care, with peak demand time occurring within 24 hours. The U.S. emergency
      care system was functioning at relatively full capacity on the basis of data
      collected for the study that showed that annually, 90% of EDs were boarding
      admitted inpatients, and 75% were diverting ambulances. CONCLUSIONS: As part of
      planning for sudden-impact disasters, communities should be expected to sustain
      medical services for 24 hours, and up to 96, before arrival of external
      resources. For effective medical surge-capacity response during sudden-impact
      disasters, there should be a priority for emergency medical care with a focus on
      ambulatory injuries and illnesses.

PMID- 16885402
TI  - A single ventilator for multiple simulated patients to meet disaster surge.
AB  - OBJECTIVES: To determine if a ventilator available in an emergency department
      could quickly be modified to provide ventilation for four adults simultaneously.
      METHODS: Using lung simulators, readily available plastic tubing, and ventilators
      (840 Series Ventilator; Puritan-Bennett), human lung simulators were added in
      parallel until the ventilator was ventilating the equivalent of four adults. Data
      collected included peak pressure, positive end-expiratory pressure, total tidal
      volume, and total minute ventilation. Any obvious asymmetry in the delivery of
      gas to the lung simulators was also documented. The ventilator was run for almost
      12 consecutive hours (5.5 hours of pressure control and more than six hours of
      volume control). RESULTS: Using readily available plastic tubing set up to
      minimize dead space volume, the four lung simulators were easily ventilated for
      12 hours using one ventilator. In pressure control (set at 25 mm H2O), the mean
      tidal volume was 1,884 mL (approximately 471 mL/lung simulator) with an average
      minute ventilation of 30.2 L/min (or 7.5 L/min/lung simulator). In volume control
      (set at 2 L), the mean peak pressure was 28 cm H2O and the minute ventilation was
      32.5 L/min total (8.1 L/min/lung simulator). CONCLUSIONS: A single ventilator may
      be quickly modified to ventilate four simulated adults for a limited time. The
      volumes delivered in this simulation should be able to sustain four 70-kg
      individuals. While further study is necessary, this pilot study suggests
      significant potential for the expanded use of a single ventilator during cases of
      disaster surge involving multiple casualties with respiratory failure.

PMID- 16885403
TI  - Nephrogenic systemic fibrosis: suspected causative role of gadodiamide used for
      contrast-enhanced magnetic resonance imaging.
AB  - Nephrogenic systemic fibrosis is a new, rare disease of unknown cause that
      affects patients with renal failure. Single cases led to the suspicion of a
      causative role of gadodiamide that is used for magnetic resonance imaging. This
      study therefore reviewed all of the authors' confirmed cases of nephrogenic
      systemic fibrosis (n = 13) with respect to clinical characteristics, gadodiamide
      exposure, and subsequent clinical course. It was found that all had been exposed
      to gadodiamide before the development of nephrogenic systemic fibrosis. The delay
      from exposure to first sign of the disease was 2 to 75 d (median 25 d). Odds
      ratio for acquiring the disease when gadodiamide exposed was 32.5 (95% confidence
      interval 1.9 to 549.2; P < 0.0001). Seven (54%) patients became severely
      disabled, and one died 21 mo after exposure. No other exposure/event than
      gadodiamide that was common to more than a minority of the patients could be
      identified. These findings indicate that gadodiamide plays a causative role in
      nephrogenic systemic fibrosis.

PMID- 16885404
TI  - Cardiovascular disease in early stages of chronic kidney disease in a Chinese
      population.
AB  - Cardiovascular disease (CVD) is one of the most serious complications of kidney
      disease, yet studies of CVD in early stage of chronic kidney disease (CKD) in
      Asian patients are very limited. Therefore, this study determined the prevalence
      and the spectrum of CVD in individuals with early-stage CKD and compared them
      with data of individuals without CKD. Compared with individuals with estimated
      GFR (eGFR) >90 ml/min per 1.73 m2, the prevalence of myocardial infarction,
      stroke, and total CVD of individuals with eGFR 60 to 89 ml/min per 1.73 m2 was
      increased by 91.4, 71.7, and 67.6%, respectively. For individuals with eGFR 30 to
      59 ml/min per 1.73 m2, the percentage was 105.2, 289.1, and 200.7%, respectively.
      For each eGFR category, stroke was more prevalent than myocardial infarction.
      Compared with individuals with eGFR >90 ml/min per 1.73 m2, participants with
      eGFR 60 to 89 and 30 to 59 ml/min per 1.73 m2 tended to have more cardiovascular
      risk factors, and there were strong unadjusted and adjusted associations between
      CVD with different stages of eGFR (eGFR >90 ml/min per 1.73 m2 as reference).
      This is the first report on the prevalence and the spectrum of CVD in early
      stages of CKD in a community-based Chinese population. The spectrum of CVD in
      this Chinese population is different from reports of Western countries.
      Individuals with subtle decreased renal function seem much more likely to have
      multiple cardiovascular risk factors and have higher prevalence of CVD than those
      without CKD.

PMID- 16885405
TI  - Adiponectin and mortality in patients with chronic kidney disease.
AB  - Adiponectin is presumed to possess antiatherogenic and cardioprotective
      properties. Limited data exist on the relationship between adiponectin and
      mortality in the earlier stages of chronic kidney disease. The Modification of
      Diet in Renal Disease study was a randomized, controlled trial that was conducted
      between 1989 and 1993. Adiponectin was measured in frozen samples that were
      obtained at baseline (N = 820). Survival status and cause of death, up to
      December 31, 2000, were obtained from the National Death Index. Multivariable Cox
      models were used to examine the relationship of adiponectin with all-cause and
      cardiovascular mortality. Mean +/- SD age was 52 +/- 12 yr, and mean +/- SD
      glomerular filtration rate (GFR) rate was 33 +/- 12 ml/min per 1.73 m2. Eighty
      five percent of participants were white, and 60% were male. Mean +/- SD
      adiponectin was 12.8 +/- 8.0 mug/ml. Triglycerides, insulin resistance, glucose,
      body mass index, GFR, C-reactive protein, and albumin were inversely related and
      proteinuria and HDL cholesterol were directly related to adiponectin. During the
      10-year follow-up period, 201 (25%) participants died of any cause, and 122 (15%)
      from cardiovascular disease. In multivariable adjusted Cox models, a 1-mug/ml
      increase in adiponectin was associated with a 3% (hazard ratio 1.03; 95%
      confidence interval 1.01 to 1.05; P = 0.02) increased risk for all-cause and 6%
      (hazard ratio 1.06; 95% confidence interval 1.03 to 1.09; P < 0.001) increased
      risk for cardiovascular mortality. High, rather than low, adiponectin is
      associated with increased mortality in this cohort of patients with chronic
      kidney disease stages 3 to 4. Further studies are necessary to confirm this
      association and to elucidate the underlying mechanisms.

PMID- 16885406
TI  - Meta-analysis: peritoneal membrane transport, mortality, and technique failure in
      peritoneal dialysis.
AB  - Peritoneal membrane solute transport in peritoneal dialysis (PD) patients is
      assessed by the peritoneal equilibration test, which measures the ratio of
      creatinine in the dialysate to plasma after a standardized 4-h dwell (D/Pc).
      Patients then are classified as high, high-average, low-average, or low
      transporters on the basis of this result. A meta-analysis of observational
      studies was carried out to characterize the relationship between D/Pc and
      mortality and technique failure in patients who are on PD. Citations were
      identified in Medline by using a combination of Medical Subject Heading search
      terms and key words related to PD, peritoneal membrane permeability/transport,
      and mortality and technique failure. The table of contents of relevant journals
      and bibliographies of relevant citations were reviewed in duplicate. Twenty
      studies that met study criteria were identified. Nineteen studies were pooled to
      generate a summary mortality relative risk of 1.15 for every 0.1 increase in the
      D/Pc (95% confidence interval 1.07 to 1.23; P < 001). This result equated to an
      increased mortality risk of 21.9, 45.7, and 77.3% in low-average, high-average,
      and high transporters, respectively, as compared with patients with low transport
      status. Meta-regression analysis showed that the proportion of patients who were
      on continuous cycler PD within a study was inversely proportional to the
      mortality risk (P = 0.05). The pooled summary relative risk for death-censored
      technique failure was 1.18 (95% confidence interval 0.96 to 1.46; P = 0.12) for
      every 0.1 increase in the D/Pc. This meta-analysis demonstrates that a higher
      peritoneal membrane solute transport rate is associated with a higher mortality
      risk and a trend to higher technique failure.

PMID- 16885407
TI  - Anti-inflammatory effect of hepatocyte growth factor in chronic kidney disease:
      targeting the inflamed vascular endothelium.
AB  - Recent studies show that hepatocyte growth factor (HGF) has potent anti
      inflammatory effects in multiple animal models of disease in various organ
      systems, including the kidney, suggesting that HGF may suppress a common
      proinflammatory process. The aim of this study was to examine the molecular
      mechanism of HGF's anti-inflammatory actions in a model of chronic kidney
      disease. Beginning 2 wk after subtotal nephrectomy, rats received a continuous
      infusion of recombinant HGF, neutralization of endogenous HGF by daily injection
      of an anti-HGF antibody, or preimmune IgG for an additional 2 wk. The effects on
      inflammation and injury were examined. HGF administration ameliorated whereas
      neutralizing endogenous HGF worsened renal inflammation in remnant kidneys. This
      was accompanied by parallel alterations in endothelial activation and
      inflammation, marked respectively by de novo E-selectin expression in renal
      vascular endothelium and leukocyte adhesion to endothelium. In vitro, HGF
      abrogated monocyte adhesion to TNF-alpha-activated endothelial monolayers and
      suppressed endothelial expression of E-selectin, which depended on NF-kappaB
      signaling. In addition, HGF suppressed NF-kappaB reporter gene activity that was
      induced by TNF-alpha and counteracted TNF-alpha-elicited NF-kappaB interaction
      with kappaB elements at the E-selectin gene level. Dissection of the NF-kappaB
      signaling cascade revealed that suppression of NF-kappaB depended on HGF's
      inhibitory action on NF-kappaB and IkappaB phosphorylation and IkappaB
      degradation. In vivo, continuous infusion of exogenous HGF markedly diminished
      sequestration of circulating fluorescence-labeled macrophages in the remnant
      kidney, mimicking the action of an E-selectin blocking antibody. These findings
      suggest that HGF has potent and direct anti-inflammatory effects on the basis of
      suppression of NF-kappaB activation and downstream endothelial inflammation.

PMID- 16885408
TI  - Multiple myeloma.

PMID- 16885409
TI  - COMP-angiopoietin-1 ameliorates renal fibrosis in a unilateral ureteral
      obstruction model.
AB  - Injury to the renal microvasculature may be a major factor in the progression of
      renal disease; therefore, protection of endothelial cells (EC) in renal
      vasculature may have a therapeutic role in renal fibrosis. Recently, a soluble,
      stable, and potent angiopoietin-1 (Ang1) variant, cartilage oligomeric matrix
      protein (COMP)-Ang1, was developed. The contribution of COMP-Ang1 in renal
      interstitial fibrosis, however, remains to be clarified. This study investigated
      the effects of COMP-Ang1 on peritubular capillary EC in the renal cortex and the
      renal fibrogenic process that is triggered by unilateral ureteral obstruction.
      COMP-Ang1 preserved renal platelet-EC adhesion molecule-1-and Tie2-positive EC.
      Morphologic examination indicated less tubular injury and tubulointerstitial
      fibrosis in mice that received COMP-Ang1 than vehicle-treated mice. Interstitial
      type I collagen and myofibroblast accumulation were significantly suppressed by
      COMP-Ang1 treatment. COMP-Ang1 increased Tie2 and Akt phosphorylation in ureteral
      obstructed kidneys. Renal surface microvasculature and renal blood flow were
      higher after treatment with COMP-Ang1 than with vehicle. COMP-Ang1 treatment
      decreased monocyte/macrophage infiltration, tissue levels of TGF-beta1, and Smad
      2/3 phosphorylation and increased Smad 7 in the obstructed kidney. These results
      demonstrate that COMP-Ang1 treatment can decrease the progression of renal
      fibrosis in unilateral ureteral obstruction. COMP-Ang1 may be an endothelium
      specific therapeutic modality in fibrotic renal disease.

PMID- 16885410
TI  - Isolation and characterization of multipotent progenitor cells from the Bowman's
      capsule of adult human kidneys.
AB  - Regenerative medicine represents a critical clinical goal for patients with ESRD,
      but the identification of renal adult multipotent progenitor cells has remained
      elusive. It is demonstrated that in human adult kidneys, a subset of parietal
      epithelial cells (PEC) in the Bowman's capsule exhibit coexpression of the stem
      cell markers CD24 and CD133 and of the stem cell-specific transcription factors
      Oct-4 and BmI-1, in the absence of lineage-specific markers. This CD24+CD133+ PEC
      population, which could be purified from cultured capsulated glomeruli, revealed
      self-renewal potential and a high cloning efficiency. Under appropriate culture
      conditions, individual clones of CD24+CD133+ PEC could be induced to generate
      mature, functional, tubular cells with phenotypic features of proximal and/or
      distal tubules, osteogenic cells, adipocytes, and cells that exhibited phenotypic
      and functional features of neuronal cells. The injection of CD24+CD133+ PEC but
      not of CD24-CD133- renal cells into SCID mice that had acute renal failure
      resulted in the regeneration of tubular structures of different portions of the
      nephron. More important, treatment of acute renal failure with CD24+CD133+ PEC
      significantly ameliorated the morphologic and functional kidney damage. This
      study demonstrates the existence and provides the characterization of a
      population of resident multipotent progenitor cells in adult human glomeruli,
      potentially opening new avenues for the development of regenerative medicine in
      patients who have renal diseases.

PMID- 16885411
TI  - Nephrocystin specifically localizes to the transition zone of renal and
      respiratory cilia and photoreceptor connecting cilia.
AB  - Nephronophthisis (NPHP) is a hereditary cystic kidney disorder that causes renal
      failure in children and young adults and can be associated with various
      extrarenal disorders, including retinitis pigmentosa. Six NPHP genes, whose
      functions are disrupted by autosomal recessive mutations in patients with NPHP,
      have been identified. The majority of patients with NPHP carry homozygous
      deletions of NPHP1 encoding nephrocystin. Previous data indicate that
      nephrocystin forms a complex at cell junctions and focal adhesions. Here, it is
      shown that nephrocystin specifically localizes at the ciliary base to the
      transition zone of renal and respiratory cilia and to photoreceptor connecting
      cilia. During in vitro ciliogenesis of primary human respiratory epithelial
      cells, nephrocystin can be detected first with a diffuse cytoplasmic localization
      as soon as cell polarization starts, and translocates to the transition zone when
      cilia are formed. In columnar respiratory cells, nephrocystin is attached tightly
      to the axonemal structure of the transition zone at a region that contains the
      calcium-sensitive cilia autotomy site. In patients with homozygous NPHP1
      deletions, nephrocystin is absent from the entire respiratory cell, including the
      transition zone, which might be of interest for future diagnostic approaches.
      Cilia formation is not altered in primary nephrocystin-deficient respiratory
      cells, which is consistent with previous findings obtained for the Caenorhabditis
      elegans ortholog. In addition, it is shown that the localization pattern of
      intraflagellar transport proteins and nephrocystin differs, suggesting distinct
      functional roles. In conclusion, nephrocystin deficiency or dysfunction at the
      transition zone of renal monocilia and the photoreceptor connecting cilium might
      explain renal failure and retinal degeneration that are observed in patients with
      NPHP1.

PMID- 16885412
TI  - Contribution of nonproteolytically activated prorenin in glomeruli to
      hypertensive renal damage.
AB  - Prorenin is activated without proteolysis by binding of prorenin receptor to the
      pentameric "handle region" (HR) of prorenin prosegment. It was hypothesized that
      such activation occurs in the kidneys of hypertensive rats and causes tissue
      renin-angiotensin system (RAS) activation and end-organ damage. Because the HR's
      binding to its binding protein made the adjacent tetrameric "gate region" (GR)
      accessible to its specific antibody, immunohistochemistry of the GR was performed
      to test the hypothesis. Methods also were devised specifically to inhibit the
      nonproteolytic activation by the decapeptide corresponding to the HR as a decoy.
      Immunohistochemistry of the GR demonstrated that the majority of
      nonproteolytically activated prorenin is present in podocytes of the kidneys from
      stroke-prone spontaneously hypertensive rats, in which activation of renal tissue
      RAS, proteinuria, and glomerulosclerosis occurred. Continuous subcutaneous
      administration of the HR decoy peptide completely inhibited both nonproteolytic
      activation of tissue prorenin and activation of tissue RAS without affecting
      circulating RAS or arterial pressure and significantly attenuated the development
      and progression of proteinuria and glomerulosclerosis. These studies clearly
      demonstrated that nonproteolytic activation of prorenin in glomeruli is
      critically involved in renal tissue RAS activation, leading to renal damage in
      hypertensive animals.

PMID- 16885413
TI  - Akt and Mammalian target of rapamycin regulate separate systems of proteolysis in
      renal tubular cells.
AB  - EGF suppresses proteolysis via class 1 phosphatidylinositol 3-kinase (PI3K) in
      renal tubular cells. EGF also increases the abundance of glycolytic enzymes
      (e.g., glyceraldehyde-3-phosphate dehydrogenase [GAPDH]) and transcription
      factors (e.g., pax2) that are degraded by the lysosomal pathway of chaperone
      mediated autophagy. To determine if EGF regulates chaperone-mediated autophagy
      through PI3K signaling, this study examined the effect of inhibiting PI3K and its
      downstream mediators Akt and the mammalian target of rapamycin (mTOR). Inhibition
      of PI3K with LY294002 prevented EGF-induced increases in GAPDH and pax2 abundance
      in NRK-52E renal tubular cells. Similar results were seen with an adenovirus
      encoding a dominant negative Akt (DN Akt). Expression of a constitutively active
      Akt increased GAPDH and pax2 abundance. An mTOR inhibitor, rapamycin, did not
      prevent EGF-induced increases in these proteins. Neither DN Akt nor rapamycin
      alone had an effect on total cell protein degradation, but both partially
      reversed EGF-induced suppression of proteolysis. DN Akt no longer affected
      proteolysis after treatment with a lysosomal inhibitor, methylamine. In contrast,
      methylamine or the inhibitor of macroautophagy, 3-methyladenine, did not prevent
      rapamycin from partially reversing the effect of EGF on proteolysis. Notably,
      rapamycin did not increase autophagasomes detected by monodansylcadaverine
      staining. Blocking the proteasomal pathway with either MG132 or lactacystin
      prevented rapamycin from partially reversing the effect of EGF on proteolysis. It
      is concluded that EGF regulates pax2 and GAPDH abundance and proteolysis through
      a PI3K/Akt-sensitive pathway that does not involve mTOR. Rapamycin has a novel
      effect of regulating proteasomal proteolysis in cells that are stimulated with
      EGF.

PMID- 16885414
TI  - Alleviation of sleep apnea in patients with chronic renal failure by nocturnal
      cycler-assisted peritoneal dialysis compared with conventional continuous
      ambulatory peritoneal dialysis.
AB  - Nocturnal hemodialysis has been shown to improve sleep apnea in patients who
      receive conventional hemodialysis. It was hypothesized that nocturnal peritoneal
      dialysis (NPD) also is effective in correcting sleep apnea in patients who
      receive continuous ambulatory PD (CAPD). Overnight polysomnography (PSG) was
      performed in 46 stable NPD and CAPD patients who were matched for demographic and
      clinical attributes. The prevalence of sleep apnea, defined as an apnea-hypopnea
      index (AHI; or frequency of apnea and hypopnea per hour of sleep) > or =15, was
      52% for NPD patients and 91% for CAPD patients (P = 0.007). The mean (+/-SD) AHI
      in NPD and CAPD patients was 31.6 +/- 25.6 and 50.9 +/- 26.4 (P = 0.025),
      respectively. For validation of the efficacy of NPD in alleviating sleep apnea, a
      fixed sequence intervention study was performed in which 24 incident PD patients
      underwent one PSG study during mandatory cycler-assisted NPD while awaiting their
      turn for CAPD training and a second PSG recording shortly after they were
      established on stable CAPD. The prevalence of sleep apnea was 4.2% during NPD and
      33.3% during CAPD (P = 0.016). AHI increased from 3.4 +/- 1.34 during NPD to 14.0
      +/- 3.46 during CAPD (P < 0.001). With the use of bioelectrical impedance
      analysis, total body water content was significantly lower during stable NPD than
      CAPD (32.8 +/- 7.37 versus 35.1 +/- 7.35 L; P = 0.004). NPD delivered greater
      reductions in total body water (-2.81 +/- 0.45 versus -1.34 +/- 0.3 L; P = 0.015)
      and hydration fraction (-3.63 +/- 0.64 versus -0.71 +/- 0.52%; P = 0.005) during
      sleep. Pulmonary function tests remained unchanged before and after conversion
      from NPD to CAPD. These findings suggest that NPD may have a therapeutic edge
      over CAPD in sleep apnea that is associated with renal failure as a result of
      better fluid clearance during sleep.

PMID- 16885415
TI  - Activity-dependent reversible inactivation of the general amino acid permease.
AB  - The general amino acid permease, Gap1p, of Saccharomyces cerevisiae transports
      all naturally occurring amino acids into yeast cells for use as a nitrogen
      source. Previous studies have shown that a nonubiquitinateable form of the
      permease, Gap1p(K9R,K16R), is constitutively localized to the plasma membrane.
      Here, we report that amino acid transport activity of Gap1p(K9R,K16R) can be
      rapidly and reversibly inactivated at the plasma membrane by the presence of
      amino acid mixtures. Surprisingly, we also find that addition of most single
      amino acids is lethal to Gap1p(K9R,K16R)-expressing cells, whereas mixtures of
      amino acids are less toxic. This toxicity appears to be the consequence of uptake
      of unusually large quantities of a single amino acid. Exploiting this toxicity,
      we isolated gap1 alleles deficient in transport of a subset of amino acids. Using
      these mutations, we show that Gap1p inactivation at the plasma membrane does not
      depend on the presence of either extracellular or intracellular amino acids, but
      does require active amino acid transport by Gap1p. Together, our findings uncover
      a new mechanism for inhibition of permease activity in response to elevated amino
      acid levels and provide a physiological explanation for the stringent regulation
      of Gap1p activity in response to amino acids.

PMID- 16885416
TI  - Loading of the 3F3/2 antigen onto kinetochores is dependent on the ordered
      assembly of the spindle checkpoint proteins.
AB  - Accurate chromosome segregation is controlled by the spindle checkpoint, which
      responds to the lack of microtubule-kinetochore attachment or of tension across
      sister kinetochores through phosphorylation of kinetochore proteins by the Mps1,
      Bub1, BubR1, Aurora B, and Plk1/Plx1 kinases. The presence of the 3F3/2
      phosphoepitope on kinetochores, generated by Plk1/Plx1-mediated phosphorylation
      of an unknown protein, correlates with the activation of the tension-sensitive
      checkpoint pathway. Using immunodepletion approach and a rephosphorylation assay
      in Xenopus extracts, we report here that not only the formation of the 3F3/2
      phosphoepitope is dependent on the checkpoint activation but also the loading of
      the 3F3/2 substrate to kinetochores requires the prior assembly of Mps1, Bub1 and
      BubR1 onto kinetochores. Interestingly, generation of the 3F3/2 epitope in
      checkpoint extracts requires the kinase activities of Mps1 and Bub1 but not that
      of BubR1. Furthermore, we demonstrate that checkpoint proteins in Xenopus
      extracts are assembled onto kinetochores in a highly ordered pathway consisting
      of three steps. Mps1 and Bub1 are loaded first, and BubR1 and Plx1 second,
      followed by Mad1 and Mad2. The characterization of this ordered assembly pathway
      provides a framework for the biochemical mechanism of the checkpoint signaling
      and will aid in the eventual identification of the 3F3/2 substrate.

PMID- 16885418
TI  - Shiga toxin facilitates its retrograde transport by modifying microtubule
      dynamics.
AB  - The bacterial exotoxin Shiga toxin is endocytosed by mammalian host cells and
      transported retrogradely through the secretory pathway before entering the
      cytosol. Shiga toxin also increases the levels of microfilaments and microtubules
      (MTs) upon binding to the cell surface. The purpose for this alteration in
      cytoskeletal dynamics is unknown. We have investigated whether Shiga toxin
      induced changes in MT levels facilitate its intracellular transport. We have
      tested the effects of the Shiga toxin B subunit (STB) on MT-dependent and 
      independent transport steps. STB increases the rate of MT-dependent Golgi stack
      repositioning after nocodazole treatment. It also enhances the MT-dependent
      accumulation of transferrin in a perinuclear recycling compartment. By contrast,
      the rate of MT-independent transferrin recycling is not significantly different
      when STB is present. We found that STB normally requires MTs and dynein for its
      retrograde transport to the juxtanuclear Golgi complex and that STB increases MT
      assembly. Furthermore, we find that MT polymerization is limiting for STB
      transport in cells. These results show that STB-induced changes in cytoskeletal
      dynamics influence intracellular transport. We conclude that the increased rate
      of MT assembly upon Shiga toxin binding facilitates the retrograde transport of
      the toxin through the secretory pathway.

PMID- 16885417
TI  - The MAPK Hog1p modulates Fps1p-dependent arsenite uptake and tolerance in yeast.
AB  - Arsenic is widely distributed in nature and all organisms possess regulatory
      mechanisms to evade toxicity and acquire tolerance. Yet, little is known about
      arsenic sensing and signaling mechanisms or about their impact on tolerance and
      detoxification systems. Here, we describe a novel role of the S. cerevisiae
      mitogen-activated protein kinase Hog1p in protecting cells during exposure to
      arsenite and the related metalloid antimonite. Cells impaired in Hog1p function
      are metalloid hypersensitive, whereas cells with elevated Hog1p activity display
      improved tolerance. Hog1p is phosphorylated in response to arsenite and this
      phosphorylation requires Ssk1p and Pbs2p. Arsenite-activated Hog1p remains
      primarily cytoplasmic and does not mediate a major transcriptional response.
      Instead, hog1delta sensitivity is accompanied by elevated cellular arsenic levels
      and we demonstrate that increased arsenite influx is dependent on the
      aquaglyceroporin Fps1p. Fps1p is phosphorylated on threonine 231 in vivo and this
      phosphorylation critically affects Fps1p activity. Moreover, Hog1p is shown to
      affect Fps1p phosphorylation. Our data are the first to demonstrate Hog1p
      activation by metalloids and provides a mechanism by which this kinase
      contributes to tolerance acquisition. Understanding how arsenite/antimonite
      uptake and toxicity is modulated may prove of value for their use in medical
      therapy.

PMID- 16885420
TI  - Delineation of the roles played by RasG and RasC in cAMP-dependent signal
      transduction during the early development of Dictyostelium discoideum.
AB  - On starvation, the cellular slime mold Dictyostelium discoideum initiates a
      program of development leading to formation of multicellular structures. The
      initial cell aggregation requires chemotaxis to cyclic AMP (cAMP) and relay of
      the cAMP signal by the activation of adenylyl cyclase (ACA), and it has been
      shown previously that the Ras protein RasC is involved in both processes.
      Insertional inactivation of the rasG gene resulted in delayed aggregation and a
      partial inhibition of early gene expression, suggesting that RasG also has a role
      in early development. Both chemotaxis and ACA activation were reduced in the rasG
      cells, but the effect on chemotaxis was more pronounced. When the responses of
      rasG- cells to cAMP were compared with the responses of rasC- and rasC- rasG-
      strains, generated in otherwise isogenic backgrounds, these studies revealed that
      signal transduction through RasG is more important in chemotaxis and early gene
      expression, but that signal transduction through RasC is more important in ACA
      activation. Because the loss of either of the two Ras proteins alone did not
      result in a total loss of signal output down either of the branches of the cAMP
      signal-response pathway, there appears to be some overlap of function.

PMID- 16885419
TI  - A functional role for the GCC185 golgin in mannose 6-phosphate receptor
      recycling.
AB  - Mannose 6-phosphate receptors (MPRs) deliver newly synthesized lysosomal enzymes
      to endosomes and then recycle to the Golgi. MPR recycling requires Rab9 GTPase;
      Rab9 recruits the cytosolic adaptor TIP47 and enhances its ability to bind to MPR
      cytoplasmic domains during transport vesicle formation. Rab9-bearing vesicles
      then fuse with the trans-Golgi network (TGN) in living cells, but nothing is
      known about how these vesicles identify and dock with their target. We show here
      that GCC185, a member of the Golgin family of putative tethering proteins, is a
      Rab9 effector that is required for MPR recycling from endosomes to the TGN in
      living cells, and in vitro. GCC185 does not rely on Rab9 for its TGN
      localization; depletion of GCC185 slightly alters the Golgi ribbon but does not
      interfere with Golgi function. Loss of GCC185 triggers enhanced degradation of
      mannose 6-phosphate receptors and enhanced secretion of hexosaminidase. These
      data assign a specific pathway to an interesting, TGN-localized protein and
      suggest that GCC185 may participate in the docking of late endosome-derived, Rab9
      bearing transport vesicles at the TGN.

PMID- 16885421
TI  - Peroneal nerve stimulation versus an ankle foot orthosis for correction of
      footdrop in stroke: impact on functional ambulation.
AB  - OBJECTIVE: To compare the efficacy of the Odstock Dropped-Foot Stimulator (ODFS),
      a transcutaneous peroneal nerve stimulation device, versus an ankle foot orthosis
      (AFO) in improving functional ambulation of chronic stroke survivors.
      INTERVENTION: Fourteen chronic stroke survivors with foot-drop participated in
      the study. Participants received ambulation training under 3 test conditions: 1)
      ODFS, 2) customized AFO, and 3) no device. Each participant was evaluated using
      the modified Emory Functional Ambulation Profile under the 3 test conditions. All
      participants were evaluated with a post-evaluation survey to solicit device
      feedback and preferences. RESULTS: Functional ambulation with the AFO was
      significantly improved, relative to no device, on the floor (P = 0.000), carpet
      (P = 0.013), and "up and go" test (P = 0.042). There was a trend toward
      significance on the obstacle (P = 0.092) and stair (P = 0.067) trials. Functional
      ambulation with the ODFS was significantly improved, relative to no device, on
      the carpet(P = 0.004). A trend toward significance on floor (P = 0.081), obstacle
      (P = 0.092), and stair (P = 0.079) trials was observed. The difference in
      functional ambulation between the AFO and ODFS showed a trend toward statistical
      significance on floor (P = 0.065) and up and go (P = 0.082) trials only. Given a
      choice between the ODFS and AFO for long-term correction of footdrop,
      participants indicated a preference for the ODFS. CONCLUSION: The AFO and the
      ODFS may be comparable in their effect on improving functional ambulation as
      compared to no device. Specific characteristics of the ODFS may make it a
      preferred intervention by stroke survivors. More rigorously controlled trials are
      needed to confirm these findings.

PMID- 16885422
TI  - Primary motor area activation during precision-demanding versus simple finger
      movement.
AB  - The authors used functional magnetic resonance imaging to explore whether the
      primary motor area (M1) serves a processing role in a finger-movement tracking
      task, emphasizing attention to accuracy, beyond its execution role of simple
      movements, with no attention to accuracy. Twenty healthy subjects performed
      alternating conditions: Rest, involving no finger movement; Track, involving
      careful control of a cursor along a target pathway with finger extension/flexion
      movements; and Move, involving finger extension/flexion movements without careful
      control. The authors compared volume of activated voxels in the M1, blood-oxygen
      level-dependent (BOLD) signal intensity of activated voxels in the M1, and BOLD
      signal intensity of all voxels in the M1 between the Track and Move conditions.
      The results showed greater volume and signal intensity in both the contralateral
      and ipsilateral M1 during Track than during Move. Overall, the results suggest
      that the M1 is engaged not only in the execution of movements but also in spatial
      and temporal processing to produce accurately controlled movements. These
      findings invite further work exploring whether precision-demanding movements,
      such as tracking, form a more potent stimulus for promoting helpful brain
      reorganization in the M1 during the recovery from stroke than simple repetitive
      movements.

PMID- 16885423
TI  - A multicenter trial of a footdrop stimulator controlled by a tilt sensor.
AB  - OBJECTIVES: To test the efficacy and acceptance of a footdrop stimulator
      controlled by a tilt sensor. METHODS: A nonrandomized, test-retest study of 26
      subjects with footdrop of more than 1 year's duration, resulting from various
      central nervous system disorders, was performed in 4 centers for at least 3
      months. Speed of walking in a straight line, speed around a figure of 8, and
      physiological cost index (PCI) were measured with and without the device.
      Hours/day and steps/day using the device were recorded. RESULTS: All but 2
      subjects used the tilt sensor at home, rather than a foot switch. Walking speed
      increased by 15% after 3 months (n = 26; P < 0.01), 32% after 6 months (n = 16; P
      < 0.01), and 47% after 12 months (n = 8; P < 0.05), while PCI decreased. The
      number of steps taken per day of use increased significantly over time, and
      increased speed was directly correlated with usage. Walking speed also increased
      with the stimulator off, but to a lesser extent, indicating a training effect.
      Subject feedback from a questionnaire indicated satisfaction with the stimulator.
      CONCLUSIONS: Both efficacy and acceptance of the stimulator were good in a
      population of subjects with chronic footdrop.

PMID- 16885425
TI  - Motor recovery as assessed with isometric finger movements and perfusion magnetic
      resonance imaging after acute ischemic stroke.
AB  - OBJECTIVE: Recovery from hemiparetic stroke is variable. An important goal for
      clinicians and clinical researchers is to identify predictors of recovery. The
      initial phase after acute ischemic stroke is considered to be of major importance
      for neurological outcome. The authors sought to determine in patients with acute
      ischemic stroke whether early motor recovery, as measured by repetitive isometric
      index-thumb oppositions, is correlated with ischemic lesion volume. METHODS:
      Thirty-six acute hemiparetic stroke patients with residual hand function were
      investigated. The European Stroke Scale (ESS) score was determined on admission
      and at discharge. Performance of repetitive index finger-thumb pinch movements
      was measured daily during the 1st 8 days after stroke onset. Brain ischemia
      volume was determined digitally in time-to-peak magnetic resonance images of per
      fusion. RESULTS: The recovery of patients with (P = 0.002) and without (P <
      0.001) thrombolysis as assessed with the ESS was paralleled by an increase in
      isometric grip force and movement rate (P < 0.05). Recovery was predicted by the
      area of moderately impaired perfusion indicated by the per-fusion mismatch volume
      (r = 0.578, P < 0.001). CONCLUSIONS: In acute stroke, recovery of hand function
      is predicted by the volume of salvageable ischemic tissue, as determined by the
      perfusion mismatch.

PMID- 16885424
TI  - Individuals with the dominant hand affected following stroke demonstrate less
      impairment than those with the nondominant hand affected.
AB  - OBJECTIVE: The purpose was to determine if upper extremity impairment and
      function in individuals with chronic stroke is dependent upon whether the
      dominant or non-dominant hand is affected. METHODS: Ninety-three community
      dwelling individuals with stroke. The Modified Ashworth Scale (tone), handheld
      dynamometry (isometric strength), monofilaments (sensation), Brief Pain Inventory
      (pain), Chedoke Arm and Hand Activity Inventory Motor Activity Log (paretic arm
      use), and Reintegration to Normal Living Index (participation) were used to form
      impairment and function models. RESULTS: Multivariate analysis models (Dominance
      x Severity) were created for impairment and function variables. There was a
      significant interaction and main effect of Dominance for the impairment model (P
      = 0.01) but not the function model (P = 0.75). The dependent variables of tone,
      grip strength, and pain were all significantly affected by Dominance, indicating
      less impairment if the dominant hand was affected. All dependent variables except
      pain were affected by Severity. CONCLUSION: This study looked at the effect of
      the dominant hand being affected versus the nondominant in individuals with
      chronic stroke. Individuals with the dominant hand affected demonstrated less
      impairment than those with the nondominant hand affected. However, there was no
      effect of dominance on paretic arm use or performance in activities of daily
      living. Prospective studies to further explore the issue of hand dominance and
      poststroke function are suggested.

PMID- 16885426
TI  - Longitudinal changes in cerebral response to proprioceptive input in individual
      patients after stroke: an FMRI study.
AB  - OBJECTIVE: Functional magnetic resonance imaging (fMRI) provides an opportunity
      to study the relationship between cerebral reorganization and functional recovery
      after stroke. The authors set out to demonstrate the feasibility of using fMRI to
      investigate mechanisms of recovery in individual patients presenting with severe
      motor impairment. METHODS: fMRI was performed during passive movement at both
      affected and unaffected wrists separately in 2 patients with pure motor stroke.
      Six scanning sessions were performed in each patient over the first 4 months
      after stroke. Seven control subjects were also studied, 1 of them over 6
      sessions. The authors examined for longitudinal changes in cerebral responses to
      proprioceptive afferent input that correlated with motor recovery. RESULTS: In
      control subjects, passive movement of either wrist led to relative increases in
      brain activation in the contralateral sensorimotor cortex and supplementary motor
      area, the bilateral inferior parietal cortex and secondary somatosensory areas,
      and the ipsilateral cerebellum. Increases in brain activation correlating with
      motor recovery were observed in both the ipsilesional primary sensory and primary
      motor cortex in 1 patient with good motor recovery but not in another patient
      with poor recovery. No longitudinal changes were seen in the control subject.
      CONCLUSIONS: These 2 case reports demonstrate that functionally relevant changes
      in cerebral organization can be identified in individual patients.

PMID- 16885427
TI  - Relationships between sensorimotor impairments and reaching deficits in acute
      hemiparesis.
AB  - OBJECTIVE: To determine the relationships between sensorimotor impairments and
      upper extremity reaching performance during the acute phase of stroke and to
      determine which, if any, measures of sensorimotor impairment can predict variance
      in reaching performance during this phase. METHODS: Sensorimotor impairments of
      upper extremity (UE) strength, active range of motion, isolated movement control,
      light touch sensation, joint position sense, spasticity, and shoulder pain were
      evaluated in a group of 46 individuals with acute hemiparesis (mean time since
      insult = 9.2 days). Subjects performed a reaching task to a target placed on
      their affected side. Three-dimensional kinematic analyses were used to assess
      reaching speed, accuracy, and efficiency. Forward stepwise multiple linear
      regression analyses were used to determine which impairment was the best
      predictor of variance in reaching performance. RESULTS: Measures of UE strength
      predicted the largest proportion of variance in the speed, accuracy, and
      efficiency of forward reaching. Isolated movement control, somatosensory
      deficits, and elbow spasticity predicted smaller amounts of variance in reaching
      performance. CONCLUSIONS: The authors' data show that deficits in strength appear
      to be the most influential sensorimotor impairment associated with limited
      reaching performance in subjects with acute hemiparesis.

PMID- 16885428
TI  - Prediction of driving after stroke: a prospective study.
AB  - BACKGROUND: The process of determining whether patients with stroke should drive
      again often involves off-road evaluations and road tests that usually take about
      2 to 3 h to complete. OBJECTIVES: This prospective study sought to identify the
      combination of tests that best predicts fitness to drive after stroke. The main
      aim was to develop a short and predictive predriving assessment battery. METHODS:
      Sixty-eight consecutive stroke patients were studied who performed a mandatory
      predriving assessment at the Belgian Road Safety Institute, Brussels, within 18
      months. Performance in a predriving assessment included medical examination (when
      needed), visual and neuropsychological evaluations, and an on-road test. Based on
      these assessments, a physician, psychologist, and the driving safety expert who
      administered the tests decided if a subject was either "fit to
      drive,""temporarily unfit to drive," or "unfit to drive." RESULTS: Logistic
      regression analysis revealed a combination of visual neglect, figure of Rey, and
      on-road tests as the model that best predicted (R(2) = 0.73) fitness to drive
      after stroke. Using a discriminant function that included the 3 tests of the
      logistic model, the fitness to drive judgments of 59 (86.8%) subjects were
      correctly predicted. The sensitivity and specificity of the predictions were
      79.4% and 94.1%, respectively. CONCLUSION: Fitness to drive after stroke can be
      predicted from performance on a few road-related tests with a high degree of
      accuracy. However, some individuals require extended assessments and further
      tests.

PMID- 16885429
TI  - Outcomes of physical therapy, speech pathology, and occupational therapy for
      people with motor neuron disease: a systematic review.
AB  - This article describes a systematic review and critical evaluation of the
      international literature on the effects of physical therapy, speech pathology,
      and occupational therapy for people with motor neuron disease (PwMND). The
      results were interpreted using the framework of the International Classification
      of Functioning, Disability and Health. This enabled us to summarize therapy
      outcomes at the level of body structure and function, activity limitations,
      participation restrictions, and quality of life. Databases searched included
      MEDLINE, PUBMED, CINAHL, PSYCInfo, Data base of Abstracts of Reviews of
      Effectiveness (DARE), The Physiotherapy Evidence data base (PEDro), Evidence
      Based Medicine Reviews (EMBASE), the Cochrane database of systematic reviews, and
      the Cochrane Controlled Trials Register. Evidence was graded according to the
      Harbour and Miller classification. Most of the evidence was found to be at the
      level of "clinical opinion" rather than of controlled clinical trials. Several
      nonrandomized small group and "observational studies" provided low-level evidence
      to support physical therapy for improving muscle strength and pulmonary function.
      There was also some evidence to support the effectiveness of speech pathology
      interventions for dysarthria. The search identified a small number of studies on
      occupational therapy for PwMND, which were small, noncontrolled pre-post-designs
      or clinical reports.

PMID- 16885430
TI  - Re: Stroke rehabilitation in Switzerland versus the United States.

PMID- 16885431
TI  - The serotonin 5-Hydroxytryptaphan1A receptor agonist, (+)8-hydroxy-2-(di-n
      propylamino)-tetralin, stimulates sympathetic-dependent increases in venous tone
      during hypovolemic shock.
AB  - Adjuvant treatment of hypovolemic shock with vasoconstrictors is controversial
      due to their propensity to raise arterial resistance and exacerbate ischemia. A
      more advantageous therapeutic approach would use agents that also promote
      venoconstriction to augment perfusion pressure through increased venous return.
      Recent studies indicate that 5-hydroxytryptophan (5-HT)(1A) receptor agonists
      increase blood pressure by stimulating sympathetic drive when administered after
      acute hypotensive hemorrhage. Given that venous tone is highly dependent upon
      sympathetic activation of alpha(2)-adrenergic receptors, we hypothesized that the
      5-HT(1A) receptor agonist, (+)8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH
      DPAT), would increase venous tone in rats subject to hypovolemic shock through
      sympathetic activation of alpha(2)-adrenergic receptors. Systemic administration
      of 8-OH-DPAT produced a sustained rise in blood pressure (+44 +/- 3 mm Hg 35 min
      after injection, P < 0.01 versus saline) and mean circulatory filling pressure
      (+4.2 +/- 0.7 mm Hg, P < 0.01 versus saline) in conscious rats subjected to
      hypovolemic shock. An equipressor infusion of epinephrine failed to influence
      mean circulatory filling pressure (MCFP). Ganglionic blockade, alpha(1)-, or
      peripheral alpha(2)-adrenergic receptor blockade prevented the rise in MCFP
      observed with 8-OH-DPAT, but only alpha(1)-adrenergic receptor blockade
      diminished the pressor effect of the drug (P < 0.01). 8-OH-DPAT raises blood
      pressure in rats in hypovolemic shock through both direct vascular activation and
      sympathetic activation of alpha(1)-adrenergic receptors. The sympathoexcitatory
      effect of 8-OH-DPAT contributes to elevated venous tone through concurrent
      activation of both alpha(1)- and alpha(2)-adrenergic receptors. The data suggest
      that 5-HT(1A) receptor agonists may provide an advantageous alternative to
      currently therapeutic interventions used to raise perfusion pressure in
      hypovolemic shock.

PMID- 16885432
TI  - Modafinil occupies dopamine and norepinephrine transporters in vivo and modulates
      the transporters and trace amine activity in vitro.
AB  - 2-[(Diphenylmethyl) sulfinyl]acetamide (modafinil), prescribed principally to
      treat narcolepsy, is undergoing assessment for other neuropsychiatric disorders
      and medical conditions. The neurochemical substrates of modafinil are unresolved.
      We postulated that modafinil enhances wakefulness by modulating dopamine (DAT),
      norepinephrine (NET), or serotonin (SERT) transporter activities. In vivo, we
      determined DAT and NET occupancy by modafinil by positron emission tomography
      imaging; in vitro, we determined modafinil activity at the DAT, NET, SERT, and
      rhesus monkey trace amine receptor 1 (TA1). In rhesus monkey, modafinil occupancy
      of striatal DAT was detected by [(11)C]2beta-carbomethoxy-3beta-4
      (fluorophenyl)tropane and of thalamic NET by [(11)C](S,S)-2-(alpha-(2
      methoxyphenoxy)-benzyl)morpholine. In vitro, modafinil effects in DAT-human
      embryonic kidney (HEK), NET-HEK, and SERT-HEK cells were investigated alone or
      combined with the TA1 receptor. Modafinil (i.v.) occupied striatal DAT sites (5
      mg/kg: 35 +/- 12%, n = 4; 8 mg/kg: 54 +/- 3%, n = 3). In thalamus, modafinil
      occupied NET sites (5 mg/kg: 16 +/- 7.8%, n = 6; 8 mg/kg: 44 +/- 12%; n = 2). In
      vitro, modafinil inhibited [(3)H]dopamine (IC(50) = 6.4 microM),
      [(3)H]norepinephrine (IC(50) = 35.6 microM), and [(3)H]serotonin (IC(50) > 500
      microM) transport via the human DAT, NET, and SERT. Modafinil did not activate
      the TA1 receptor in TA1-HEK cells, but it augmented a monoamine transporter
      dependent enhancement of phenethylamine activation of TA1 in TA1-DAT and TA1-NET
      cells, but not in TA1-SERT cells. The present data provide compelling evidence
      that modafinil occupies the DAT and NET in living brain of rhesus monkeys and
      raise the possibility that modafinil affects wakefulness by interacting with
      catecholamine transporters in brain.

PMID- 16885433
TI  - Dopamine transporter (DAT) inhibitors alleviate specific parkinsonian deficits in
      monkeys: association with DAT occupancy in vivo.
AB  - Viable dopamine neurons in Parkinson's disease express the dopamine transporter
      (DAT) and release dopamine (DA). We postulated that potent DAT inhibitors, with
      low affinity for the serotonin transporter (SERT), may elevate endogenously
      released extracellular dopamine levels to provide therapeutic benefit. The
      therapeutic potential of eight DAT inhibitors was investigated in 1-methyl-4
      phenyl-1,2,3,6-tetrahydropyridine-treated cynomolgus monkeys (Macaca
      fascicularis), with efficacy correlated with DAT occupancy as determined by
      positron emission tomography imaging in striatum. Four potent DAT inhibitors,
      with relatively high norepinephrine transporter, but low SERT affinities, that
      occupied the DAT improved activity in parkinsonian monkeys, whereas three high
      affinity DAT inhibitors with low DAT occupancy did not. 2beta-Carbomethoxy-3alpha
      (3,4-dichlorophenyl)-7beta-hydroxy-8-methyl-8-azabicyclo[3.2.1.]octane (O-1163)
      occupied the DAT but had short-lived pharmacological effects. The benztropine
      analog difluoropine increased general activity, improved posture, reduced body
      freeze, and produced sleep disturbances at high doses. (1R)-2beta-(1-Propanoyl)
      3alpha-(4-fluorophenyl)tropane (O-1369) alleviated parkinsonian signs in advanced
      parkinsonian monkeys, by increasing general activity, improving posture, reducing
      body freeze, and sedation, but not significantly reducing bradykinesia or
      increasing locomotor activity. In comparison with the D(2)-D(3) DA receptor
      agonist quinelorane, O-1369 elicited oral/facial dyskinesias, whereas quinelorane
      did not improve posture or reduce balance and promoted stereotypy. In conclusion,
      DAT inhibitors with therapeutic potential combine high DAT affinity in vitro and
      high DAT occupancy of brain striatum in vivo with enduring day-time effects that
      do not extend into the nighttime. Advanced parkinsonian monkeys (80% DAT loss)
      respond more effectively to DAT inhibitors than mild parkinsonian monkeys (46%
      DAT loss). The therapeutic potential of dopamine transport inhibitors for
      Parkinson's disease warrants preclinical investigation.

PMID- 16885434
TI  - Protein-translocating trimeric autotransporters of gram-negative bacteria.

PMID- 16885435
TI  - AI-3 synthesis is not dependent on luxS in Escherichia coli.
AB  - The quorum-sensing (QS) signal autoinducer-2 (AI-2) has been proposed to promote
      interspecies signaling in a broad range of bacterial species. AI-2 is
      spontaneously derived from 4,5-dihydroxy-2,3-pentanedione that, along with
      homocysteine, is produced by cleavage of S-adenosylhomocysteine (SAH) and S
      ribosylhomocysteine by the Pfs and LuxS enzymes. Numerous phenotypes have been
      attributed to AI-2 QS signaling using luxS mutants. We have previously reported
      that the luxS mutation also affects the synthesis of the AI-3 autoinducer that
      activates enterohemorrhagic Escherichia coli virulence genes. Here we show that
      several species of bacteria synthesize AI-3, suggesting a possible role in
      interspecies bacterial communication. The luxS mutation leaves the cell with only
      one pathway, involving oxaloacetate and l-glutamate, for de novo synthesis of
      homocysteine. The exclusive use of this pathway for homocysteine production
      appears to alter metabolism in the luxS mutant, leading to decreased levels of AI
      3. The addition of aspartate and expression of an aromatic amino acid
      transporter, as well as a tyrosine-specific transporter, restored AI-3-dependent
      phenotypes in an luxS mutant. The defect in AI-3 production, but not in AI-2
      production, in the luxS mutant was restored by expressing the Pseudomonas
      aeruginosa S-adenosylhomocysteine hydrolase that synthesizes homocysteine
      directly from SAH. Furthermore, phenotype microarrays revealed that the luxS
      mutation caused numerous metabolic deficiencies, while AI-3 signaling had little
      effect on metabolism. This study examines how AI-3 production is affected by the
      luxS mutation and explores the roles of the LuxS/AI-2 system in metabolism and
      QS.

PMID- 16885437
TI  - Growth phase-dependent expression of drug exporters in Escherichia coli and its
      contribution to drug tolerance.
AB  - Drug exporters contribute to the intrinsic drug resistance in many organisms.
      Although there are at least 20 exporter genes in Escherichia coli, most of them
      apparently do not confer drug resistance in complex laboratory media except for
      the AcrAB, EmrE, and MdfA efflux systems. In this study, we comprehensively
      investigated the growth phase-dependent expression of drug exporter genes. The
      expression of acrAB, emrAB, emrD, emrE, emrKY, mdfA, and ydgFE is stable at
      moderate levels during any growth phase, whereas mdtEF promoter activity greatly
      increased with cell growth and reached the maximum level at the late stationary
      phase. The growth phase-dependent increase in mdtEF expression was also observed
      on quantitative reverse transcription-PCR analysis. As expected from the
      transporter expression, the stationary-phase cells actually showed MdtEF
      dependent tolerance to drugs and toxic dyes. Growth phase-dependent elevation of
      mdtEF expression was found to be mediated by the stationary-phase sigma factor
      rpoS and the RpoS-dependent signaling pathway, Hfq, GadY, and GadX. The induction
      level was decreased by tnaAB deletion, suggesting that indole sensing stimulates
      this process.

PMID- 16885436
TI  - The GrlR-GrlA regulatory system coordinately controls the expression of flagellar
      and LEE-encoded type III protein secretion systems in enterohemorrhagic
      Escherichia coli.
AB  - The gene function of the locus of enterocyte effacement (LEE) is essential for
      full virulence of enterohemorrhagic Escherichia coli (EHEC). Strict control of
      LEE gene expression is mediated by the coordinated activities of several
      regulatory elements. We previously reported that the ClpX/ClpP protease
      positively controls LEE expression by down-regulating intracellular levels of
      GrlR, a negative regulator of LEE gene expression. We further revealed that the
      negative effect of GrlR on LEE expression was mediated through GrlA, a positive
      regulator of LEE expression. In this study, we found that the FliC protein, a
      major component of flagellar filament, was overproduced in clpXP mutant EHEC, as
      previously reported for Salmonella. We further found that FliC expression was
      reduced in a clpXP grlR double mutant. To determine the mediators of this
      phenotype, FliC protein levels in wild-type, grlR, grlA, and grlR grlA strains
      were compared. Steady-state levels of FliC protein were reduced only in the grlR
      mutant, suggesting that positive regulation of FliC expression by GrlR is
      mediated by GrlA. Correspondingly, cell motility was also reduced in the grlR
      mutant, but not in the grlA or grlR grlA mutant. Because overexpression of grlA
      from a multicopy plasmid strongly represses the FliC level, as well as cell
      motility, we conclude that GrlA acts as a negative regulator of flagellar-gene
      expression. The fact that an EHEC strain constitutively expressing FlhD/FlhC
      cannot adhere to HeLa cells leads us to hypothesize that GrlA-dependent
      repression of the flagellar regulon is important for efficient cell adhesion of
      EHEC to host cells.

PMID- 16885438
TI  - Requirement for Vibrio cholerae integration host factor in conjugative DNA
      transfer.
AB  - The requirement for host factors in the transmission of integrative and
      conjugative elements (ICEs) has not been extensively explored. Here we tested
      whether integration host factor (IHF) or Fis, two host-encoded nucleoid proteins,
      are required for transfer of SXT, a Vibrio cholerae-derived ICE that can be
      transmitted to many gram-negative species. Fis did not influence the transfer of
      SXT to or from V. cholerae. In contrast, IHF proved to be required for V.
      cholerae to act as an SXT donor. In the absence of IHF, V. cholerae displayed a
      modest defect for serving as an SXT recipient. Surprisingly, SXT integration into
      or excision from the V. cholerae chromosome, which requires an SXT-encoded
      integrase related to lambda integrase, did not require IHF. Therefore, the defect
      in SXT transmission in the V. cholerae IHF mutant is probably not related to
      IHF's ability to promote DNA recombination. The V. cholerae IHF mutant was also
      highly impaired as a donor of RP4, a broad-host-range conjugative plasmid. Thus,
      the V. cholerae IHF mutant appears to have a general defect in conjugation.
      Escherichia coli IHF mutants were not impaired as donors or recipients of SXT or
      RP4, indicating that IHF is a V. cholerae-specific conjugation factor.

PMID- 16885439
TI  - Activity of Rhodobacter sphaeroides RpoHII, a second member of the heat shock
      sigma factor family.
AB  - We have identified a second RpoH homolog, RpoH(II), in the alpha-proteobacterium
      Rhodobacter sphaeroides. Primary amino acid sequence comparisons demonstrate that
      R. sphaeroides RpoH(II) belongs to a phylogenetically distinct group with RpoH
      orthologs from alpha-proteobacteria that contain two rpoH genes. Like its
      previously identified paralog, RpoH(I), RpoH(II) is able to complement the
      temperature-sensitive phenotype of an Escherichia coli sigma(32) (rpoH) mutant.
      In addition, we show that recombinant RpoH(I) and RpoH(II) each transcribe two E.
      coli sigma(32)-dependent promoters (rpoD P(HS) and dnaK P1) when reconstituted
      with E. coli core RNA polymerase. We observed differences, however, in the
      ability of each sigma factor to recognize six R. sphaeroides promoters (cycA P1,
      groESL(1), rpoD P(HS), dnaK P1, hslO, and ecfE), all of which resemble the E.
      coli sigma(32) promoter consensus. While RpoH(I) reconstituted with R.
      sphaeroides core RNA polymerase transcribed all six promoters, RpoH(II) produced
      detectable transcripts from only four promoters (cycA P1, groESL(1), hslO, and
      ecfE). These results, in combination with previous work demonstrating that an
      RpoH(I) mutant mounts a typical heat shock response, suggest that while RpoH(I)
      and RpoH(II) have redundant roles in response to heat, they may also have roles
      in response to other environmental stresses.

PMID- 16885440
TI  - Class 1 integrons potentially predating the association with tn402-like
      transposition genes are present in a sediment microbial community.
AB  - Integrons are genetic elements that contribute to lateral gene transfer in
      bacteria as a consequence of possessing a site-specific recombination system.
      This system facilitates the spread of genes when they are part of mobile
      cassettes. Most integrons are contained within chromosomes and are confined to
      specific bacterial lineages. However, this is not the case for class 1 integrons,
      which were the first to be identified and are one of the single biggest
      contributors to multidrug-resistant nosocomial infections, carrying resistance to
      many antibiotics in diverse pathogens on a global scale. The rapid spread of
      class 1 integrons in the last 60 years is partly a result of their association
      with a specific suite of transposition functions, which has facilitated their
      recruitment by plasmids and other transposons. The widespread use of antibiotics
      has acted as a positive selection pressure for bacteria, especially pathogens,
      which harbor class 1 integrons and their associated antibiotic resistance genes.
      Here, we have isolated bacteria from soil and sediment in the absence of
      antibiotic selection. Class 1 integrons were recovered from four different
      bacterial species not known to be human pathogens or commensals. All four
      integrons lacked the transposition genes previously considered to be a
      characteristic of this class. At least two of these integrons were located on a
      chromosome, and none of them possessed antibiotic resistance genes. We conclude
      that novel class 1 integrons are present in a sediment environment in various
      bacteria of the beta-proteobacterial class. These data suggest that the dispersal
      of this class may have begun before the "antibiotic era."

PMID- 16885442
TI  - The global regulator Spx functions in the control of organosulfur metabolism in
      Bacillus subtilis.
AB  - Spx is a global transcriptional regulator of the oxidative stress response in
      Bacillus subtilis. Its target is RNA polymerase, where it contacts the alpha
      subunit C-terminal domain. Recently, evidence was presented that Spx participates
      in sulfate-dependent control of organosulfur utilization operons, including the
      ytmI, yxeI, ssu, and yrrT operons. The yrrT operon includes the genes that
      function in cysteine synthesis from S-adenosylmethionine through intermediates S
      adenosylhomocysteine, ribosylhomocysteine, homocysteine, and cystathionine. These
      operons are also negatively controlled by CymR, the repressor of cysteine
      biosynthesis operons. All of the operons are repressed in media containing
      cysteine or sulfate but are derepressed in medium containing the alternative
      sulfur source, methionine. Spx was found to negatively control the expression of
      these operons in sulfate medium, in part, by stimulating the expression of the
      cymR gene. In addition, microarray analysis, monitoring of yrrT-lacZ fusion
      expression, and in vitro transcription studies indicate that Spx directly
      activates yrrT operon expression during growth in medium containing methionine as
      sole sulfur source. These experiments have uncovered additional roles for Spx in
      the control of gene expression during unperturbed, steady-state growth.

PMID- 16885441
TI  - The Bordetella bfe system: growth and transcriptional response to siderophores,
      catechols, and neuroendocrine catecholamines.
AB  - Ferric enterobactin utilization by Bordetella bronchiseptica and Bordetella
      pertussis requires the BfeA outer membrane receptor. Under iron-depleted growth
      conditions, transcription of bfeA is activated by the BfeR regulator by a
      mechanism requiring the siderophore enterobactin. In this study, enterobactin
      inducible bfeA transcription was shown to be TonB independent. To determine
      whether other siderophores or nonsiderophore catechols could be utilized by the
      Bfe system, various compounds were tested for the abilities to promote the growth
      of iron-starved B. bronchiseptica and induce bfeA transcription. The BfeA
      receptor transported ferric salmochelin, corynebactin, and the synthetic
      siderophores TRENCAM and MECAM. Salmochelin and MECAM induced bfeA transcription
      in iron-starved Bordetella cells, but induction by corynebactin and TRENCAM was
      minimal. The neuroendocrine catecholamines epinephrine, norepinephrine, and
      dopamine exhibited a remarkable capacity to induce transcription of bfeA.
      Norepinephrine treatment of B. bronchiseptica resulted in BfeR-dependent bfeA
      transcription, elevated BfeA receptor production, and growth stimulation.
      Pyrocatechol, carbidopa, and isoproterenol were similarly strong inducers of bfeA
      transcription, whereas tyramine and 3,4-dihydroxymandelic acid demonstrated low
      inducing activity. The results indicate that the inducer structure requires a
      catechol group for function and that the ability to induce bfeA transcription
      does not necessarily correlate with the ability to stimulate bacterial growth.
      The expanded range of catechol siderophores transported by the BfeA receptor
      demonstrates the potential versatility of the Bordetella Bfe iron retrieval
      system. The finding that catecholamine neurotransmitters activate bfeA
      transcription and promote growth suggests that Bordetella cells can perceive and
      may benefit from neuroendocrine catecholamines on the respiratory epithelium.

PMID- 16885443
TI  - Interaction of TonB with the outer membrane receptor FpvA of Pseudomonas
      aeruginosa.
AB  - Pyoverdine-mediated iron uptake by the FpvA receptor in the outer membrane of
      Pseudomonas aeruginosa is dependent on the inner membrane protein TonB1. This
      energy transducer couples the proton-electrochemical potential of the inner
      membrane to the transport event. To shed more light upon this process, a
      recombinant TonB1 protein lacking the N-terminal inner membrane anchor (TonB(pp))
      was constructed. This protein was, after expression in Escherichia coli, purified
      from the soluble fraction of lysed cells by means of an N-terminal hexahistidine
      or glutathione S-transferase (GST) tag. Purified GST-TonB(pp) was able to capture
      detergent-solubilized FpvA, regardless of the presence of pyoverdine or
      pyoverdine-Fe. Targeting of the TonB1 fragment to the periplasm of P. aeruginosa
      inhibited the transport of ferric pyoverdine by FpvA in vivo, indicating an
      interference with endogenous TonB1, presumably caused by competition for binding
      sites at the transporter or by formation of nonfunctional TonB heterodimers.
      Surface plasmon resonance experiments demonstrated that the FpvA-TonB(pp)
      interactions have apparent affinities in the micromolar range. The binding of
      pyoverdine or ferric pyoverdine to FpvA did not modulate this affinity.
      Apparently, the presence of either iron or pyoverdine is not essential for the
      formation of the FpvA-TonB complex in vitro.

PMID- 16885444
TI  - Two transsulfurylation pathways in Klebsiella pneumoniae.
AB  - In most bacteria, inorganic sulfur is assimilated into cysteine, which provides
      sulfur for methionine biosynthesis via transsulfurylation. Here, cysteine is
      transferred to the terminal carbon of homoserine via its sulfhydryl group to form
      cystathionine, which is cleaved to yield homocysteine. In the enteric bacteria
      Escherichia coli and Salmonella enterica, these reactions are catalyzed by
      irreversible cystathionine-gamma-synthase and cystathionine-beta-lyase enzymes.
      Alternatively, yeast and some bacteria assimilate sulfur into homocysteine, which
      serves as a sulfhydryl group donor in the synthesis of cysteine by reverse
      transsulfurylation with a cystathionine-beta-synthase and cystathionine-gamma
      lyase. Herein we report that the related enteric bacterium Klebsiella pneumoniae
      encodes genes for both transsulfurylation pathways; genetic and biochemical
      analyses show that they are coordinately regulated to prevent futile cycling.
      Klebsiella uses reverse transsulfurylation to recycle methionine to cysteine
      during periods of sulfate starvation. This methionine-to-cysteine (mtc)
      transsulfurylation pathway is activated by cysteine starvation via the CysB
      protein, by adenosyl-phosphosulfate starvation via the Cbl protein, and by
      methionine excess via the MetJ protein. While mtc mutants cannot use methionine
      as a sulfur source on solid medium, they will utilize methionine in liquid medium
      via a sulfide intermediate, suggesting that an additional nontranssulfurylation
      methionine-to-cysteine recycling pathway(s) operates under these conditions.

PMID- 16885445
TI  - DksA is required for growth phase-dependent regulation, growth rate-dependent
      control, and stringent control of fis expression in Escherichia coli.
AB  - DksA is a critical transcription factor in Escherichia coli that binds to RNA
      polymerase and potentiates control of rRNA promoters and certain amino acid
      promoters. Given the kinetic similarities between rRNA promoters and the fis
      promoter (Pfis), we investigated the possibility that DksA might also control
      transcription from Pfis. We show that the absence of dksA extends transcription
      from Pfis well into the late logarithmic and stationary growth phases,
      demonstrating the importance of DksA for growth phase-dependent regulation of
      fis. We also show that transcription from Pfis increases with steady-state growth
      rate and that dksA is absolutely required for this regulation. In addition, both
      DksA and ppGpp are required for inhibition of Pfis promoter activity following
      amino acid starvation, and these factors act directly and synergistically to
      negatively control Pfis transcription in vitro. DksA decreases the half-life of
      the intrinsically short-lived fis promoter-RNA polymerase complex and increases
      its sensitivity to the concentration of CTP, the predominant initiating
      nucleotide triphosphate for this promoter. This work extends our understanding of
      the multiple factors controlling fis expression and demonstrates the generality
      of the DksA requirement for regulation of kinetically similar promoters.

PMID- 16885448
TI  - Cross-functionality of nitrogenase components NifH1 and VnfH in Anabaena
      variabilis.
AB  - Anabaena variabilis fixes nitrogen under aerobic growth conditions in
      differentiated cells called heterocysts using either a Mo nitrogenase or a V
      nitrogenase. The nifH1 gene, which encodes the dinitrogenase reductase of the Mo
      nitrogenase that is expressed only in heterocysts, is cotranscribed with nifD1
      and nifK1, which together encode the Mo dinitrogenase. These genes were expressed
      in the presence or absence of molybdate or vanadate. The vnfH gene, which encodes
      the dinitrogenase reductase of the V nitrogenase, was located about 23 kb from
      vnfDGK, which encodes the V dinitrogenase; however, like vnfDGK, vnfH was
      expressed only in the absence of molybdate, with or without vanadate. Like nifH1,
      the vnfH gene was expressed exclusively in heterocysts under either aerobic or
      anaerobic growth conditions and thus is under the control of developmental
      factors. The vnfH mutant was able to grow diazotrophically using the V
      nitrogenase, because NifH1, which was also made in cells starved for molybdate,
      could substitute for VnfH. Under oxic conditions, the nifH1 mutant grew in the
      absence of molybdate but not in its presence, using VnfH, while the nifH1 vnfH
      double mutant did not grow diazotrophically with or without molybdate or
      vanadate. A nifH1 mutant that expressed nifDK and vnfH but not vnfDGK was able to
      grow and fix nitrogen normally, indicating that VnfH could substitute for NifH in
      the Mo nitrogenase and that these dinitrogenase reductases are not involved in
      determining the metal specificity of the Mo nitrogenase or the V nitrogenase.

PMID- 16885446
TI  - Global regulatory impact of ClpP protease of Staphylococcus aureus on regulons
      involved in virulence, oxidative stress response, autolysis, and DNA repair.
AB  - Staphylococcus aureus is an important pathogen, causing a wide range of
      infections including sepsis, wound infections, pneumonia, and catheter-related
      infections. In several pathogens ClpP proteases were identified by in vivo
      expression technologies to be important for virulence. Clp proteolytic complexes
      are responsible for adaptation to multiple stresses by degrading accumulated and
      misfolded proteins. In this report clpP, encoding the proteolytic subunit of the
      ATP-dependent Clp protease, was deleted, and gene expression of DeltaclpP was
      determined by global transcriptional analysis using DNA-microarray technology.
      The transcriptional profile reveals a strong regulatory impact of ClpP on the
      expression of genes encoding proteins that are involved in the pathogenicity of
      S. aureus and adaptation of the pathogen to several stresses. Expression of the
      agr system and agr-dependent extracellular virulence factors was diminished.
      Moreover, the loss of clpP leads to a complete transcriptional derepression of
      genes of the CtsR- and HrcA-controlled heat shock regulon and a partial
      derepression of genes involved in oxidative stress response, metal homeostasis,
      and SOS DNA repair controlled by PerR, Fur, MntR, and LexA. The levels of
      transcription of genes encoding proteins involved in adaptation to anaerobic
      conditions potentially regulated by an Fnr-like regulator were decreased.
      Furthermore, the expression of genes whose products are involved in autolysis was
      deregulated, leading to enhanced autolysis in the mutant. Our results indicate a
      strong impact of ClpP proteolytic activity on virulence, stress response, and
      physiology in S. aureus.

PMID- 16885447
TI  - A functional dlt operon, encoding proteins required for incorporation of d
      alanine in teichoic acids in gram-positive bacteria, confers resistance to
      cationic antimicrobial peptides in Streptococcus pneumoniae.
AB  - Streptococcus pneumoniae is one of the few species within the group of low-G +C
      gram-positive bacteria reported to contain no d-alanine in teichoic acids,
      although the dltABCD operon encoding proteins responsible for d-alanylation is
      present in the genomes of two S. pneumoniae strains, the laboratory strain R6 and
      the clinical isolate TIGR4. The annotation of dltA in R6 predicts a protein, d
      alanine-d-alanyl carrier protein ligase (Dcl), that is shorter at the amino
      terminus than all other Dcl proteins. Translation of dltA could also start
      upstream of the annotated TTG start codon at a GTG, resulting in the premature
      termination of dltA translation at a stop codon. Applying a novel integrative
      translation probe plasmid with Escherichia coli 'lacZ as a reporter, we could
      demonstrate that dltA translation starts at the upstream GTG. Consequently, S.
      pneumoniae R6 is a dltA mutant, whereas S. pneumoniae D39, the parental strain of
      R6, and Rx, another derivative of D39, contained intact dltA genes. Repair of the
      stop codon in dltA of R6 and insertional inactivation of dltA in D39 and Rx
      yielded pairs of dltA-deficient and dltA-proficient strains. Subsequent
      phenotypic analysis showed that dltA inactivation resulted in enhanced
      sensitivity to the cationic antimicrobial peptides nisin and gallidermin, a
      phenotype fully consistent with those of dltA mutants of other gram-positive
      bacteria. In addition, mild alkaline hydrolysis of heat-inactivated whole cells
      released d-alanine from dltA-proficient strains, but not from dltA mutants. The
      results of our study suggest that, as in many other low-G+C gram-positive
      bacteria, teichoic acids of S. pneumoniae contain d-alanine residues in order to
      protect this human pathogen against the actions of cationic antimicrobial
      peptides.

PMID- 16885449
TI  - Distinguishing characteristics of hyperrecombinogenic RecA protein from
      Pseudomonas aeruginosa acting in Escherichia coli.
AB  - In Escherichia coli, a relatively low frequency of recombination exchanges (FRE)
      is predetermined by the activity of RecA protein, as modulated by a complex
      regulatory program involving both autoregulation and other factors. The RecA
      protein of Pseudomonas aeruginosa (RecA(Pa)) exhibits a more robust recombinase
      activity than its E. coli counterpart (RecA(Ec)). Low-level expression of
      RecA(Pa) in E. coli cells results in hyperrecombination (an increase of FRE) even
      in the presence of RecA(Ec). This genetic effect is supported by the biochemical
      finding that the RecA(Pa) protein is more efficient in filament formation than
      RecA K72R, a mutant protein with RecA(Ec)-like DNA-binding ability. Expression of
      RecA(Pa) also partially suppresses the effects of recF, recO, and recR mutations.
      In concordance with the latter, RecA(Pa) filaments initiate recombination equally
      from both the 5' and 3' ends. Besides, these filaments exhibit more resistance to
      disassembly from the 5' ends that makes the ends potentially appropriate for
      initiation of strand exchange. These comparative genetic and biochemical
      characteristics reveal that multiple levels are used by bacteria for a programmed
      regulation of their recombination activities.

PMID- 16885450
TI  - Global gene expression analysis of the heat shock response in the phytopathogen
      Xylella fastidiosa.
AB  - Xylella fastidiosa is a phytopathogenic bacterium that is responsible for
      diseases in many economically important crops. Although different strains have
      been studied, little is known about X. fastidiosa stress responses. One of the
      better characterized stress responses in bacteria is the heat shock response,
      which induces the expression of specific genes to prevent protein misfolding and
      aggregation and to promote degradation of the irreversibly denatured
      polypeptides. To investigate X. fastidiosa genes involved in the heat shock
      response, we performed a whole-genome microarray analysis in a time course
      experiment. Globally, 261 genes were induced (9.7%) and 222 genes were repressed
      (8.3%). The expression profiles of the differentially expressed genes were
      grouped, and their expression patterns were validated by quantitative reverse
      transcription-PCR experiments. We determined the transcription start sites of six
      heat shock-inducible genes and analyzed their promoter regions, which allowed us
      to propose a putative consensus for sigma(32) promoters in Xylella and to suggest
      additional genes as putative members of this regulon. Besides the induction of
      classical heat shock protein genes, we observed the up-regulation of virulence
      associated genes such as vapD and of genes for hemagglutinins, hemolysin, and
      xylan-degrading enzymes, which may indicate the importance of heat stress to
      bacterial pathogenesis. In addition, we observed the repression of genes related
      to fimbriae, aerobic respiration, and protein biosynthesis and the induction of
      genes related to the extracytoplasmic stress response and some phage-related
      genes, revealing the complex network of genes that work together in response to
      heat shock.

PMID- 16885451
TI  - Mutator and antimutator effects of the bacteriophage P1 hot gene product.
AB  - The Hot (homolog of theta) protein of bacteriophage P1 can substitute for the
      Escherichia coli DNA polymerase III theta subunit, as evidenced by its
      stabilizing effect on certain dnaQ mutants that carry an unstable polymerase III
      epsilon proofreading subunit (antimutator effect). Here, we show that Hot can
      also cause an increase in the mutability of various E. coli strains (mutator
      effect). The hot mutator effect differs from the one caused by the lack of theta.
      Experiments using chimeric theta/Hot proteins containing various domains of Hot
      and theta along with a series of point mutants show that both N- and C-terminal
      parts of each protein are important for stabilizing the epsilon subunit. In
      contrast, the N-terminal part of Hot appears uniquely responsible for its mutator
      activity.

PMID- 16885452
TI  - Methionine sulfoxide reductase in Helicobacter pylori: interaction with
      methionine-rich proteins and stress-induced expression.
AB  - The reductive repair of oxidized methionine residues performed by methionine
      sulfoxide reductase is important for the gastric pathogen Helicobacter pylori to
      maintain persistent stomach colonization. Methionine-containing proteins that are
      targeted for repair by Msr were identified from whole-cell extracts (after cells
      were exposed to O(2) stress) by using a coimmunoprecipitation approach. Proteins
      identified as Msr-interacting included catalase, GroEL, thioredoxin-1 (Trx1), and
      site-specific recombinase; with one exception (Trx1, the reductant for Msr) all
      these proteins have approximately twofold higher methionine (Met) content than
      other proteins. These Met-rich proteins were purified and were shown to
      individually form a cross-linked adduct with Msr. Catalase-specific activity in
      an msr strain was one-half that of the parent strain; this difference was only
      observed under oxidative stress conditions, and the activity was restored to
      nearly wild-type levels by adding Msr plus dithiothreitol to msr strain extracts.
      In agreement with the cross-linking study, pure Msr used Trx1 but not Trx2 as a
      reductant. Comparative structure modeling classified the H. pylori Msr in class
      II within the MsrB family, like the Neisseria enzymes. Pure H. pylori enzyme
      reduced only the R isomer of methyl p-tolyl-sulfoxide with an apparent K(m) of
      4.1 mM for the substrate. Stress conditions (peroxide, peroxynitrite, and iron
      starvation) all caused approximately 3- to 3.5-fold transcriptional up-regulation
      of msr. Neither the O(2) level during growth nor the use of background regulatory
      mutants had a significant effect on msr transcription. Late log and stationary
      phase cultures had the highest Msr protein levels and specific activity.

PMID- 16885453
TI  - N-acetyl-d-glucosamine induces the expression of multidrug exporter genes, mdtEF,
      via catabolite activation in Escherichia coli.
AB  - The expression of MdtEF, a multidrug exporter in Escherichia coli, is positively
      controlled through multiple signaling pathways, but little is known about signals
      that induce MdtEF expression. In this study, we investigated compounds that
      induce the expression of the mdtEF genes and found that out of 20 drug exporter
      genes in E. coli, the expression of mdtEF is greatly induced by N-acetyl-d
      glucosamine (GlcNAc). The induction of mdtEF by GlcNAc is not mediated by the
      evgSA, ydeO, gadX, and rpoS signaling pathways that have been known to regulate
      mdtEF expression. On the other hand, deletion of the nagE gene, encoding the
      phosphotransferase (PTS) system for GlcNAc, prevented induction by GlcNAc. The
      induction of mdtEF by GlcNAc was also greatly inhibited by the addition of cyclic
      AMP (cAMP) and completely abolished upon deletion of the cAMP receptor protein
      gene (crp). Other PTS sugars, glucose and d-glucosamine, also induced mdtEF gene
      expression. These results suggest that mdtEF expression is stimulated through
      catabolite control.

PMID- 16885454
TI  - TrzN from Arthrobacter aurescens TC1 Is a zinc amidohydrolase.
AB  - TrzN, the broad-specificity triazine hydrolase from Arthrobacter and Nocardioides
      spp., is reportedly in the amidohydrolase superfamily of metalloenzymes, but
      previous studies suggested that a metal was not required for activity. To help
      resolve that conundrum, a double chaperone expression system was used to produce
      multimilligram quantities of functionally folded, recombinant TrzN. The TrzN
      obtained from Escherichia coli (trzN) cells cultured with increasing zinc in the
      growth medium showed corresponding increases in specific activity, and enzyme
      obtained from cells grown with 500 muM zinc showed maximum activity. Recombinant
      TrzN contained 1 mole of Zn per mole of TrzN subunit. Maximally active TrzN was
      not affected by supplementation with most metals nor by EDTA, consistent with
      previous observations (E. Topp, W. M. Mulbry, H. Zhu, S. M. Nour, and D. Cuppels,
      Appl. Environ. Microbiol. 66:3134-3141, 2000) which had led to the conclusion
      that TrzN is not a metalloenzyme. Fully active native TrzN showed a loss of
      greater than 90% of enzyme activity and bound zinc when treated with the metal
      chelator 8-hydroxyquinoline-5-sulfonic acid. While exogenously added zinc or
      cobalt restored activity to metal-depleted TrzN, cobalt supported lower activity
      than did zinc. Iron, manganese, nickel, and copper did not support TrzN activity.
      Both Zn- and Co-TrzN showed different relative activities with different s
      triazine substrates. Co-TrzN showed a visible absorption spectrum characteristic
      of other members of the amidohydrolase superfamily replaced with cobalt.

PMID- 16885456
TI  - The nitric oxide-responsive regulator NsrR controls ResDE-dependent gene
      expression.
AB  - The ResD-ResE signal transduction system is essential for aerobic and anaerobic
      respiration in Bacillus subtilis. ResDE-dependent gene expression is induced by
      oxygen limitation, but full induction under anaerobic conditions requires nitrite
      or nitric oxide (NO). Here we report that NsrR (formerly YhdE) is responsible for
      the NO-dependent up-regulation of the ResDE regulon. The null mutation of nsrR
      led to aerobic derepression of hmp (flavohemoglobin gene) partly in a ResDE
      independent manner. In addition to its negative role in aerobic hmp expression,
      NsrR plays an important role under anaerobic conditions for regulation of ResDE
      controlled genes, including hmp. ResDE-dependent gene expression was increased by
      the nsrR mutation in the absence of NO, but the expression was decreased by the
      mutation when NO was present. Consequently, B. subtilis cells lacking NsrR no
      longer sense and respond to NO (and nitrite) to up-regulate the ResDE regulon.
      Exposure to NO did not significantly change the cellular concentration of NsrR,
      suggesting that NO likely modulates the activity of NsrR. NsrR is similar to the
      recently described nitrite- or NO-sensitive transcription repressors present in
      various bacteria. NsrR likely has an Fe-S cluster, and interaction of NO with the
      Fe-S center is proposed to modulate NsrR activity.

PMID- 16885457
TI  - Rippling is a predatory behavior in Myxococcus xanthus.
AB  - Cells of Myxococcus xanthus will, at times, organize their movement such that
      macroscopic traveling waves, termed ripples, are formed as groups of cells glide
      together on a solid surface. The reason for this behavior has long been a
      mystery, but we demonstrate here that rippling is a feeding behavior which occurs
      when M. xanthus cells make direct contact with either prey or large
      macromolecules. Rippling has been observed during two fundamentally distinct
      environmental conditions: (i) starvation-induced fruiting body development and
      (ii) predation of other organisms. Our results indicate that case (i) does not
      occur in all wild-type strains and is dependent on the intrinsic level of
      autolysis. Analysis of predatory rippling indicates that rippling behavior is
      inducible during predation on proteobacteria, gram-positive bacteria, yeast (such
      as Saccharomyces cerevisiae), and phage. Predatory efficiency decreases under
      genetic and physiological conditions in which rippling is inhibited. Rippling
      will also occur in the presence of purified macromolecules such as peptidoglycan,
      protein, and nucleic acid but does not occur in the presence of the respective
      monomeric components and also does not occur when the macromolecules are
      physically separated from M. xanthus cells. We conclude that rippling behavior is
      a mechanism utilized to efficiently consume nondiffusing growth substrates and
      that developmental rippling is a result of scavenging lysed cell debris.

PMID- 16885455
TI  - Characterization of the pilin ortholog of the Helicobacter pylori type IV cag
      pathogenicity apparatus, a surface-associated protein expressed during infection.
AB  - The Helicobacter pylori cag pathogenicity island (cag PAI) encodes components of
      a type IV secretion system (T4SS) involved in host interaction and pathogenicity.
      Previously, seven cag PAI proteins were identified as homologs of Agrobacterium
      tumefaciens Vir proteins, which form a paradigm T4SS. The T pilus composed of the
      processed VirB2 pilin is an external structural part of the A. tumefaciens T4SS.
      In H. pylori, cag-dependent assembly of pili has not been observed so far, nor
      has a pilin (VirB2) ortholog been characterized. We have here identified, using a
      motif-based search, an H. pylori cag island protein (HP0546) that possesses
      sequence and predicted structural similarities to VirB2-like pilins of other
      T4SSs. The HP0546 protein displays interstrain variability in its terminal
      domains. HP0546 was expressed as a FLAG-tagged fusion protein in Escherichia
      coli, A. tumefaciens, and H. pylori and was detected as either two or three bands
      of different molecular masses in the insoluble fraction, indicating protein
      processing. As reported previously, isogenic H. pylori mutants in the putative
      cag pilin gene had reduced abilities to induce cag PAI-dependent interleukin-8
      secretion in gastric epithelial cells. Fractionation analysis of H. pylori, using
      a specific antiserum raised against an N-terminal HP0546 peptide, showed that the
      protein is partially surface exposed and that its surface localization depended
      upon an intact cag system. By immunoelectron microscopy, HP0546 was localized in
      surface appendages, with surface exposure of an N-terminal epitope. Pronounced
      strain-to-strain variability of this predicted surface-exposed part of HP0546
      indicates a strong selective pressure for variation in vivo.

PMID- 16885458
TI  - Salicylic acid activates sigma factor B by rsbU-dependent and -independent
      mechanisms.
AB  - Salicylic acid (SAL) may impact Staphylococcus aureus virulence by activating the
      sigB operon (rsbU-V-W-sigB), thus leading to reductions in alpha-toxin production
      and decreased fibronectin binding (L. I. Kupferwasser et al., J. Clin. Investig.
      112:222-233, 2003). As these prior studies were performed in strain RN6390 (an
      rsbU mutant) and its rsbU-repaired variant, SH1000, the current investigation was
      designed to determine if the SAL effect occurs via rsbU- and/or rsbV-dependent
      pathways in an rsbU-intact S. aureus strain (FDA486). We thus quantified the
      transcription from two sigB-dependent promoters (asp23 and sarA P3) in FDA486 in
      response to SAL exposure in vitro, using isogenic single-knockout constructs of
      rsbU, rsbV, or rsbW and a green fluorescent protein reporter system. SAL induced
      sarA P3 and asp23 promoter activities in a dose-dependent manner in the parental
      strain. In contrast, sigB activation by SAL was progressively more mitigated in
      the rsbU and rsbV mutants. As predicted, SAL caused significant reductions in
      both alpha-toxin production and fibrinogen and fibronectin binding in the
      parental strain. The extent of these reductions, compared with the parent, was
      reduced in the rsb mutants (rsbV > rsbU), especially at low SAL concentrations.
      Since generation of the free SigB protein usually requires a sequential rsbU-V-W
      sigB activation cascade, the present phenotypic and genotypic data suggest key
      roles for both rsbU and rsbV in SAL-mediated activation of sigB in strains with a
      fully intact sigB operon.

PMID- 16885459
TI  - Paired-end sequence mapping detects extensive genomic rearrangement and
      translocation during divergence of Francisella tularensis subsp. tularensis and
      Francisella tularensis subsp. holarctica populations.
AB  - Comparative genome hybridization of the Francisella tularensis subsp. tularensis
      and F. tularensis subsp. holarctica populations have shown that genome content is
      highly conserved, with relatively few genes in the F. tularensis subsp.
      tularensis genome being absent in other F. tularensis subspecies. To determine if
      organization of the genome differs between global populations of F. tularensis
      subsp. tularensis and F. tularensis subsp. holarctica, we have used paired-end
      sequence mapping (PESM) to identify regions of the genome where synteny is
      broken. The PESM approach compares the physical distances between paired-end
      sequencing reads of a library of a wild-type reference F. tularensis subsp.
      holarctica strain to the predicted lengths between the reads based on map
      coordinates of two different F. tularensis genome sequences. A total of 17
      different continuous regions were identified in the F. tularensis subsp.
      holarctica genome (CR(holar)(c)(tica)) which are noncontiguous in the F.
      tularensis subsp. tularensis genome. Six of the 17 different CR(holarctica) are
      positioned as adjacent pairs in the F. tularensis subsp. tularensis genome
      sequence but are translocated in F. tularensis subsp. holarctica, implying that
      their arrangements are ancestral in F. tularensis subsp. tularensis and derived
      in F. tularensis subsp. holarctica. PCR analysis of the CR(holarctica) in 88
      additional F. tularensis subsp. tularensis and F. tularensis subsp. holarctica
      isolates showed that the arrangements of the CR(holarctica) are highly conserved,
      particularly in F. tularensis subsp. holarctica, consistent with the hypothesis
      that global populations of F. tularensis subsp. holarctica have recently
      experienced a periodic selection event or they have emerged from a recent clonal
      expansion. Two unique F. tularensis subsp. tularensis-like strains were also
      observed which likely are derived from evolutionary intermediates and may
      represent a new taxonomic unit.

PMID- 16885460
TI  - A novel branching enzyme of the GH-57 family in the hyperthermophilic archaeon
      Thermococcus kodakaraensis KOD1.
AB  - Branching enzyme (BE) catalyzes formation of the branch points in glycogen and
      amylopectin by cleavage of the alpha-1,4 linkage and its subsequent transfer to
      the alpha-1,6 position. We have identified a novel BE encoded by an
      uncharacterized open reading frame (TK1436) of the hyperthermophilic archaeon
      Thermococcus kodakaraensis KOD1. TK1436 encodes a conserved protein showing
      similarity to members of glycoside hydrolase family 57 (GH-57 family). At the C
      terminus of the TK1436 protein, two copies of a helix-hairpin-helix (HhH) motif
      were found. TK1436 orthologs are distributed in archaea of the order
      Thermococcales, cyanobacteria, some actinobacteria, and a few other bacterial
      species. When recombinant TK1436 protein was incubated with amylose used as the
      substrate, a product peak was detected by high-performance anion-exchange
      chromatography, eluting more slowly than the substrate. Isoamylase treatment of
      the reaction mixture significantly increased the level of short-chain alpha
      glucans, indicating that the reaction product contained many alpha-1,6 branching
      points. The TK1436 protein showed an optimal pH of 7.0, an optimal temperature of
      70 degrees C, and thermostability up to 90 degrees C, as determined by the iodine
      staining assay. These properties were the same when a protein devoid of HhH
      motifs (the TK1436DeltaH protein) was used. The average molecular weight of
      branched glucan after reaction with the TK1436DeltaH protein was over 100 times
      larger than that of the starting substrate. These results clearly indicate that
      TK1436 encodes a structurally novel BE belonging to the GH-57 family.
      Identification of an overlooked BE species provides new insights into glycogen
      biosynthesis in microorganisms.

PMID- 16885461
TI  - The entry mechanism of membrane-containing phage Bam35 infecting Bacillus
      thuringiensis.
AB  - The temperate double-stranded DNA bacteriophage Bam35 infects gram-positive
      Bacillus thuringiensis cells. Bam35 has an icosahedral protein coat surrounding
      the viral membrane that encloses the linear 15-kbp DNA genome. The protein coat
      of Bam35 uses the same assembly principle as that of PRD1, a lytic bacteriophage
      infecting gram-negative hosts. In this study, we dissected the process of Bam35
      entry into discrete steps: receptor binding, peptidoglycan penetration, and
      interaction with the plasma membrane (PM). Bam35 very rapidly adsorbs to the cell
      surface, and N-acetyl-muramic acid is essential for Bam35 binding. Zymogram
      analysis demonstrated that peptidoglycan-hydrolyzing activity is associated with
      the Bam35 virion. We showed that the penetration of Bam35 through the PM is a
      divalent-cation-dependent process, whereas adsorption and peptidoglycan digestion
      are not.

PMID- 16885462
TI  - Cyclic AMP-dependent osmoregulation of crp gene expression in Escherichia coli.
AB  - We have found that the cyclic AMP (cAMP) receptor protein (CRP)-cAMP regulatory
      complex in Escherichia coli is subject to osmoregulation at the level of crp gene
      expression. This osmoregulation was lost in a cya mutant strain but could be
      restored by external addition of cAMP, suggesting that the intracellular level of
      cAMP is a key factor in the osmoregulation of CRP. The ability of the cell to
      maintain optimal CRP activity was essential for the growth and survival of the
      bacteria under low-osmolarity conditions as shown by studies with different crp
      mutant alleles. A suppressor mutant with a novel amino acid substitution (L124R)
      in CRP showed restored growth at low osmolarity. CRP(L124R) was not activated by
      cAMP and was shown to be dominant negative over the wild type. Our findings
      suggest that the fine-tuning of the CRP activity may be critical for bacterial
      viability and adaptability to changing osmotic conditions.

PMID- 16885463
TI  - Membrane vesicles: an overlooked component of the matrices of biofilms.
AB  - The matrix helps define the architecture and infrastructure of biofilms and also
      contributes to their resilient nature. Although many studies continue to define
      the properties of both gram-positive and gram-negative bacterial biofilms, there
      is still much to learn, especially about how structural characteristics help
      bridge the gap between the chemistry and physical aspects of the matrix. Here, we
      show that membrane vesicles (MVs), structures derived from the outer membrane of
      gram-negative bacteria, are a common particulate feature of the matrix of
      Pseudomonas aeruginosa biofilms. Biofilms grown using different model systems and
      growth conditions were shown to contain MVs when thin sectioned for transmission
      electron microscopy, and mechanically disrupted biofilms revealed MVs in
      association with intercellular material. MVs were also isolated from biofilms by
      employing techniques for matrix isolation and a modified MV isolation protocol.
      Together these observations verified the presence and frequency of MVs and
      indicated that MVs were a definite component of the matrix. Characterization of
      planktonic and biofilm-derived MVs revealed quantitative and qualitative
      differences between the two and indicated functional roles, such as proteolytic
      activity and binding of antibiotics. The ubiquity of MVs was supported by
      observations of biofilms from a variety of natural environments outside the
      laboratory and established MVs as common biofilm constituents. MVs appear to be
      important and relatively unacknowledged particulate components of the matrix of
      gram-negative or mixed bacterial biofilms.

PMID- 16885464
TI  - Relationship among several key cell cycle events in the developmental
      cyanobacterium Anabaena sp. strain PCC 7120.
AB  - When grown in the absence of a source of combined nitrogen, the filamentous
      cyanobacterium Anabaena sp. strain PCC 7120 develops, within 24 h, a
      differentiated cell type called a heterocyst that is specifically involved in the
      fixation of N(2). Cell division is required for heterocyst development,
      suggesting that the cell cycle could control this developmental process. In this
      study, we investigated several key events of the cell cycle, such as cell growth,
      DNA synthesis, and cell division, and explored their relationships to heterocyst
      development. The results of analyses by flow cytometry indicated that the DNA
      content increased as the cell size expanded during cell growth. The DNA content
      of heterocysts corresponded to the subpopulation of vegetative cells that had a
      big cell size, presumably those at the late stages of cell growth. Consistent
      with these results, most proheterocysts exhibited two nucleoids, which were
      resolved into a single nucleoid in most mature heterocysts. The ring structure of
      FtsZ, a protein required for the initiation of bacterial cell division, was
      present predominantly in big cells and rarely in small cells. When cell division
      was inhibited and consequently cells became elongated, little change in DNA
      content was found by measurement using flow cytometry, suggesting that inhibition
      of cell division may block further synthesis of DNA. The overexpression of minC,
      which encodes an inhibitor of FtsZ polymerization, led to the inhibition of cell
      division, but cells expanded in spherical form to become giant cells; structures
      with several cells attached together in the form of a cloverleaf could be seen
      frequently. These results may indicate that the relative amounts of FtsZ and MinC
      affect not only cell division but also the placement of the cell division planes
      and the cell morphology. MinC overexpression blocked heterocyst differentiation,
      consistent with the requirement of cell division in the control of heterocyst
      development.

PMID- 16885465
TI  - Feedback-resistant mutations in Bacillus subtilis glutamine synthetase are
      clustered in the active site.
AB  - The feedback-inhibited form of Bacillus subtilis glutamine synthetase regulates
      the activity of the TnrA transcription factor through a protein-protein
      interaction that prevents TnrA from binding to DNA. Five mutants containing
      feedback-resistant glutamine synthetases (E65G, S66P, M68I, H195Y, and P318S)
      were isolated by screening for colonies capable of cross-feeding Gln(-) cells. In
      vitro enzymatic assays revealed that the mutant enzymes had increased resistance
      to inhibition by glutamine, AMP, and methionine sulfoximine. The mutant proteins
      had a variety of enzymatic alterations that included changes in the levels of
      enzymatic activity and in substrate K(m) values. Constitutive expression of TnrA-
      and GlnR-regulated genes was seen in all five mutants. In gel mobility shift
      assays, the E65G and S66P enzymes were unable to inhibit TnrA DNA binding, while
      the other three mutant proteins (M68I, H195Y, and P318S) showed partial
      inhibition of TnrA DNA binding. A homology model of B. subtilis glutamine
      synthetase revealed that the five mutated amino acid residues are located in the
      enzyme active site. These observations are consistent with the hypothesis that
      glutamine and AMP bind at the active site to bring about feedback inhibition of
      glutamine synthetase.

PMID- 16885466
TI  - Complete DNA sequence of a ColBM plasmid from avian pathogenic Escherichia coli
      suggests that it evolved from closely related ColV virulence plasmids.
AB  - Avian pathogenic Escherichia coli (APEC), an extraintestinal pathogenic E. coli
      causing colibacillosis in birds, is responsible for significant economic losses
      for the poultry industry. Recently, we reported that the APEC pathotype was
      characterized by possession of a set of genes contained within a 94-kb cluster
      linked to a ColV plasmid, pAPEC-O2-ColV. These included sitABCD, genes of the
      aerobactin operon, hlyF, iss, genes of the salmochelin operon, and the 5' end of
      cvaB of the ColV operon. However, the results of gene prevalence studies
      performed among APEC isolates revealed that these traits were not always linked
      to ColV plasmids. Here, we present the complete sequence of a 174-kb plasmid,
      pAPEC-O1-ColBM, which contains a putative virulence cluster similar to that of
      pAPEC-O2-ColV. These two F-type plasmids share remarkable similarity, except that
      they encode the production of different colicins; pAPEC-O2-ColV contains an
      intact ColV operon, and pAPEC-O1-ColBM encodes the colicins B and M.
      Interestingly, remnants of the ColV operon exist in pAPEC-O1-ColBM, hinting that
      ColBM-type plasmids may have evolved from ColV plasmids. Among APEC isolates, the
      prevalence of ColBM sequences helps account for the previously observed
      differences in prevalence between genes of the "conserved" portion of the
      putative virulence cluster of pAPEC-O2-ColV and those genes within its "variable"
      portion. These results, in conjunction with Southern blotting and probing of
      representative ColBM-positive strains, indicate that this "conserved" cluster of
      putative virulence genes is primarily linked to F-type virulence plasmids among
      the APEC isolates studied.

PMID- 16885467
TI  - Transport of multidrug resistance substrates by the Streptococcus agalactiae
      hemolysin transporter.
AB  - Streptococcus agalactiae (group B streptococcus [GBS]) causes neonatal sepsis,
      pneumonia, and meningitis, as well as infections of the bovine udder. The S.
      agalactiae hemolysin is regarded as an important virulence factor, and hemolysin
      expression is dependent on the cyl gene cluster. cylA and cylB encode the ATP
      binding and transmembrane domains of a typical ATP binding cassette (ABC)
      transporter. The deduced proteins contain the signature sequence of a multidrug
      resistance (MDR) transporter, and mutation of the genes results in a nonhemolytic
      and nonpigmented phenotype. To further elucidate the function of the putative
      transporter, nonpolar deletion mutants of cylA were constructed. These mutants
      are nonhemolytic and can be complemented by the transporter genes. Wild-type
      strain and nonhemolytic cylA and cylK deletion mutants were exposed to known
      substrates of MDR transporters. Mutation of cylA significantly impaired growth in
      the presence of daunorubicin, doxorubicin, and rhodamine 6G and resulted in a
      decreased export of doxorubicin from the cells. The mutation of cylK, a gene of
      unknown function located downstream from cylA, caused a loss of hemolysis but had
      no effect on the transport of MDR substrates. Furthermore, the hemolytic activity
      of the wild-type strain was inhibited by reserpine in a dose-dependent manner. We
      conclude that CylAB closely resembles an ABC-type MDR transporter and propose
      that the GBS hemolysin molecule represents a natural substrate of the
      transporter.

PMID- 16885468
TI  - Solution structure of the conserved hypothetical protein Rv2302 from
      Mycobacterium tuberculosis.
AB  - The Mycobacterium tuberculosis protein Rv2302 (80 residues; molecular mass of 8.6
      kDa) has been characterized using nuclear magnetic resonance (NMR) and circular
      dichroism (CD) spectroscopy. While the biochemical function of Rv2302 is still
      unknown, recent microarray analyses show that Rv2302 is upregulated in response
      to starvation and overexpression of heat shock proteins and, consequently, may
      play a role in the biochemical processes associated with these events. Rv2302 is
      a monomer in solution as shown by size exclusion chromatography and NMR
      spectroscopy. CD spectroscopy suggests that Rv2302 partially unfolds upon heating
      and that this unfolding is reversible. Using NMR-based methods, the solution
      structure of Rv2302 was determined. The protein contains a five-strand,
      antiparallel beta-sheet core with one C-terminal alpha-helix (A61 to A75) nestled
      against its side. Hydrophobic interactions between residues in the alpha-helix
      and beta-strands 3 and 4 hold the alpha-helix near the beta-sheet core. The
      electrostatic potential on the solvent-accessible surface is primarily negative
      with the exception of a positive arginine pocket composed of residues R18, R70,
      and R74. Steady-state {(1)H}-(15)N heteronuclear nuclear Overhauser effects
      indicate that the protein's core is rigid on the picosecond timescale. The
      absence of amide cross-peaks for residues G13 to H19 in the (1)H-(15)N
      heteronuclear single quantum correlation spectrum suggests that this region, a
      loop between beta-strands 1 and 2, undergoes motion on the millisecond to
      microsecond timescale. Dali searches using the structure closest to the average
      structure do not identify any high similarities to any other known protein
      structure, suggesting that the structure of Rv2302 may represent a novel protein
      fold.

PMID- 16885470
TI  - Analysis of the terminus region of the Caulobacter crescentus chromosome and
      identification of the dif site.
AB  - The terminus region of the Caulobacter crescentus chromosome and the dif
      chromosome dimer resolution site were characterized. The Caulobacter genome
      contains skewed sequences that abruptly switch strands at dif and may have roles
      in chromosome maintenance and segregation. Absence of dif or the XerCD
      recombinase results in a chromosome segregation defect. The Caulobacter terminus
      region is unusual, since it contains many essential or highly expressed genes.

PMID- 16885469
TI  - Comparison of the genome sequence of the poultry pathogen Bordetella avium with
      those of B. bronchiseptica, B. pertussis, and B. parapertussis reveals extensive
      diversity in surface structures associated with host interaction.
AB  - Bordetella avium is a pathogen of poultry and is phylogenetically distinct from
      Bordetella bronchiseptica, Bordetella pertussis, and Bordetella parapertussis,
      which are other species in the Bordetella genus that infect mammals. In order to
      understand the evolutionary relatedness of Bordetella species and further the
      understanding of pathogenesis, we obtained the complete genome sequence of B.
      avium strain 197N, a pathogenic strain that has been extensively studied. With
      3,732,255 base pairs of DNA and 3,417 predicted coding sequences, it has the
      smallest genome and gene complement of the sequenced bordetellae. In this study,
      the presence or absence of previously reported virulence factors from B. avium
      was confirmed, and the genetic bases for growth characteristics were elucidated.
      Over 1,100 genes present in B. avium but not in B. bronchiseptica were
      identified, and most were predicted to encode surface or secreted proteins that
      are likely to define an organism adapted to the avian rather than the mammalian
      respiratory tracts. These include genes coding for the synthesis of a
      polysaccharide capsule, hemagglutinins, a type I secretion system adjacent to two
      very large genes for secreted proteins, and unique genes for both
      lipopolysaccharide and fimbrial biogenesis. Three apparently complete prophages
      are also present. The BvgAS virulence regulatory system appears to have
      polymorphisms at a poly(C) tract that is involved in phase variation in other
      bordetellae. A number of putative iron-regulated outer membrane proteins were
      predicted from the sequence, and this regulation was confirmed experimentally for
      five of these.

PMID- 16885471
TI  - Peptidyl-prolyl cis/trans isomerase-independent functional NifH mutant of
      Azotobacter vinelandii.
AB  - Peptidyl-prolyl cis/trans isomerases (PPIases) play a pivotal role in catalyzing
      the correct folding of many prokaryotic and eukaryotic proteins that are
      implicated in a variety of biological functions, ranging from cell cycle
      regulation to bacterial infection. The nif accessory protein NifM, which is
      essential for the biogenesis of a functional NifH component of nitrogenase, is a
      PPIase. To understand the nature of the molecular signature that defines the NifM
      dependence of NifH, we screened a library of nifH mutants in the nitrogen-fixing
      bacterium Azotobacter vinelandii for mutants that acquired NifM independence.
      Here, we report that NifH can acquire NifM independence when the conserved Pro258
      located in the C-terminal region of NifH, which wraps around the other subunit in
      the NifH dimer, is replaced by serine.

PMID- 16885472
TI  - Two GacA-dependent small RNAs modulate the quorum-sensing response in Pseudomonas
      aeruginosa.
AB  - In Pseudomonas aeruginosa, the GacS/GacA two-component system positively controls
      the quorum-sensing machinery and the expression of extracellular products via two
      small regulatory RNAs, RsmY and RsmZ. An rsmY rsmZ double mutant and a gacA
      mutant were similarly impaired in the synthesis of the quorum-sensing signal N
      butanoyl-homoserine lactone, the disulfide bond-forming enzyme DsbA, and the
      exoproducts hydrogen cyanide, pyocyanin, elastase, chitinase (ChiC), and chitin
      binding protein (CbpD). Both mutants showed increased swarming ability, azurin
      release, and early biofilm development.

PMID- 16885473
TI  - The mycobacterium-specific gene Rv2719c is DNA damage inducible independently of
      RecA.
AB  - The mycobacterium-specific gene Rv2719c was found to be expressed primarily from
      a promoter that was clearly DNA damage inducible independently of RecA. Upstream
      of the transcriptional start site for this promoter, sequence motifs resembling
      those observed previously at the RecA-independent, DNA damage-inducible recA
      promoter were identified, and the -10 motif was demonstrated by mutational
      analysis in transcriptional fusion constructs to be important for expression of
      Rv2719c.

PMID- 16885475
TI  - The case for patient-centered care in orthopaedics.
AB  - Now is a critical time to develop a patient-centered care model in the field of
      orthopaedic surgery. Patient-centered care is defined by the American Academy of
      Orthopaedic Surgeons as the provision of safe, effective, and timely
      musculoskeletal care achieved through cooperation between the orthopaedic
      surgeon; an informed, respected patient (and family); and a coordinated health
      care team. Patient-centered care, a paradigm shift from disease-centered care, is
      being championed by government agencies, patient advocacy groups, and insurance
      companies. Orthopaedic organizations must develop a comprehensive education
      program to provide surgeons the tools they need to navigate this paradigm shift.

PMID- 16885474
TI  - The Bacillus subtilis DivIVA protein has a sporulation-specific proximity to
      Spo0J.
AB  - The Bacillus subtilis DivIVA protein controls the positioning of the division
      site and the relocation of the chromosome during sporulation. By performing
      coimmunoprecipitation experiments, we demonstrated that a myc-DivIVA protein is
      in proximity to FtsZ and MinD during vegetative growth and Spo0J during the first
      120 min of sporulation.

PMID- 16885476
TI  - Hip resurfacing arthroplasty.

PMID- 16885477
TI  - Hip resurfacing arthroplasty.
AB  - Hip resurfacing arthroplasty is a type of hip replacement that involves capping
      the femoral head and preserving bone of the proximal femur. Metal-on-metal
      surface replacements have been manufactured since the early 1990s. Recent studies
      indicate excellent clinical results with low failure rates at 1- to 5-year follow
      up. Although these early results are encouraging, resurfacing devices must be
      used with caution because less is known about their long-term safety and
      efficacy. The best candidates for resurfacing are patients younger than age 60
      years with good bone stock. The surgical approach is similar to that for standard
      total hip replacements, but with slightly more dissection because the femoral
      head must be preserved and displaced to visualize the acetabulum. To reduce
      complications, resurfacing arthroplasty should be performed by surgeons who have
      received training specifically in this technique.

PMID- 16885478
TI  - Recurrent posterior shoulder instability.
AB  - Recurrent posterior shoulder instability is an uncommon condition. It is often
      unrecognized, leading to incorrect diagnoses, delays in diagnosis, and even
      missed diagnoses. Posterior instability encompasses a wide spectrum of pathology,
      ranging from unidirectional posterior subluxation to multidirectional instability
      to locked posterior dislocations. Nonsurgical treatment of posterior shoulder
      instability is successful in most cases; however, surgical intervention is
      indicated when conservative treatment fails. For optimal results, the surgeon
      must accurately define the pattern of instability and address all soft-tissue and
      bony injuries present at the time of surgery. Arthroscopic treatment of posterior
      shoulder instability has increased application, and a variety of techniques has
      been described to manage posterior glenohumeral instability related to posterior
      capsulolabral injury.

PMID- 16885479
TI  - Nonsurgical management of acute and chronic low back pain.
AB  - A variety of nonsurgical treatment alternatives exists for acute and chronic low
      back pain. Patients should receive appropriate education about the favorable
      natural history of low back pain, basic body mechanics, and methods (eg,
      exercises, activity modification, behavioral modification) that can reduce
      symptoms. Nonprescription medication is efficacious for mild to moderate pain.
      Nonsteroidal anti-inflammatory drugs, alone or in combination with muscle
      relaxants, relieve pain and improve overall symptoms of acute low back pain.
      Exercise therapy has limited value for acute low back pain, but strong evidence
      supports exercise therapy in the management of chronic low back pain. Moderately
      strong evidence supports the use of manipulation in acute back pain. Evidence is
      weak for the use of epidural corticosteroid injections in patients with acute low
      back pain, strong for short-term relief of chronic low back pain, and limited for
      long-term relief of chronic low back pain. The use of facet injections in the
      management of acute low back pain is not supported by evidence, nor is the
      effectiveness of orthoses, traction, magnets, or acupuncture. Trigger point
      injections are not indicated for nonspecific acute or chronic low back pain, and
      sacroiliac joint injections are not indicated in the routine management of low
      back pain. Conflicting evidence exists regarding the use of transcutaneous
      electrical nerve stimulation.

PMID- 16885481
TI  - The floating shoulder.
AB  - The floating shoulder is an uncommon but important injury pattern. Although it is
      frequently defined as an ipsilateral fracture of the clavicle and scapular neck,
      recent studies suggest that ligament disruption associated with a scapular neck
      fracture contributes to the functional equivalent of this injury pattern, with or
      without an associated clavicle fracture. Determining the specific injury patterns
      indicates the potential for significant instability, and correlating these
      patterns with clinical outcome is a challenge. Because the degree of ligament
      disruption is difficult to assess on radiographs, indications for nonsurgical and
      surgical management are not well defined. Minimally displaced fractures typically
      do well with nonsurgical care. However, the degree of fracture displacement and
      ligament disruption that results in less predictable outcomes after nonsurgical
      treatment is uncertain, and the indications for surgery can be controversial.
      Internal fixation of a displaced clavicle fracture restores the contour of the
      shoulder, regulates soft-tissue tension, and often indirectly reduces the
      scapular neck fracture. Fixation of both fractures is recommended in certain
      fracture patterns. Because these controversies cannot be resolved by current
      evidence, surgeons must choose an individualized approach based on an
      understanding of the pathoanatomy and personal experience.

PMID- 16885480
TI  - Spondylolysis and spondylolisthesis in children and adolescents: II. Surgical
      management.
AB  - Surgical management is indicated for children and adolescents with spondylolysis
      and low-grade spondylolisthesis (< or =50% slip) who fail to respond to
      nonsurgical measures. In situ posterolateral L5 to S1 fusion is the best option
      for those with a low-grade slip secondary to L5 pars defects or dysplastic
      spondylolisthesis at the lumbosacral junction. Pars repair is reserved for
      patients with symptomatic spondylolysis and low-grade, mobile spondylolisthesis
      with pars defects cephalad to L5 and for those with multiple-level defects. Screw
      repair of the pars defect, wiring transverse process to spinous process, and
      pedicle screw-laminar hook fixation are surgical options. The ideal surgical
      management of high-grade spondylolisthesis (>50% slip) is controversial. Spinal
      fusion has been indicated for children and adolescents with high-grade
      spondylolisthesis regardless of symptoms. In situ L4 to S1 fusion with cast
      immobilization is safe and effective for alleviating back pain and neurologic
      symptoms. Instrumented reduction and fusion techniques permit improved correction
      of sagittal spinal imbalance and more rapid rehabilitation but are associated
      with a higher risk of iatrogenic nerve root injuries than in situ techniques.
      Wide decompression of nerve roots combined with instrumented partial reduction
      may diminish the risk of neurologic complications. Pseudarthrosis and neurologic
      injury presenting as L5 radiculopathy and sacral root dysfunction are the most
      common complications associated with surgical management of high-grade
      spondylolisthesis.

PMID- 16885482
TI  - The international code of marketing of breastmilk substitutes: the challenge is
      choice.

PMID- 16885484
TI  - Boxing neonate on an engorged breast--a new behavior identified.

PMID- 16885483
TI  - Heat treating breast milk as an infant feeding option.

PMID- 16885486
TI  - Breast milk: an unappreciated source of stem cells.

PMID- 16885487
TI  - Trends in exclusive breastfeeding: findings from the 1990s.
AB  - This article presents trends and differentials in exclusive breastfeeding
      patterns that occurred in developing settings during the 1990s and considers
      these trends in relation to the breastfeeding-support activities in that decade.
      Between 1990 and 2000, the data suggest that exclusive breast-feeding levels in
      the developing world increased 15% overall among infants younger than 4 months
      (from 46% to 53%) and among infants older than 6 months (from 34% to 39%). The
      increase in urban areas is of special note. Urban areas are presumed to be most
      susceptible to the ambient health system and social and commercial pressures
      against breastfeeding; the support activities of the 1990s (eg, the Baby-friendly
      Hospital Initiative and the International Code of Marketing of Breastmilk
      Substitutes) were developed to address these pressures. Given this,
      implementation of the Global Strategy for Infant and Young Child Feeding, which
      supports these proven interventions, should be effective in further increasing
      optimal breast-feeding practices.

PMID- 16885488
TI  - The conceptualization of perceived insufficient milk among Mexican mothers.
AB  - This study sought to provide a comprehensive picture of maternal
      conceptualization of Perceived Insufficient Milk (PIM) using qualitative methods
      (semistructured interviews, free lists, and rankings) in Mexico. Two hundred and
      seven first-time mothers of infants younger than 6 months and mothers-to-be who
      were (or intended to be) breastfeeding were interviewed in waiting areas at a
      hospital and a health clinic in Mexico City, Mexico, from September 2000 to
      January 2001. Pattern searching and triangulation of the 3 qualitative methods
      indicated that women viewed crying as the chief symptom of PIM. Maternal diet and
      liquid intake were cited as both the most salient causes and treatments for PIM.
      The main coping strategy in the event of PIM was formula feeding. These findings
      highlight the need for addressing maternal concerns in relation to PIM,
      especially regarding the role of crying as the initiator of the PIM cycle.

PMID- 16885489
TI  - Factors influencing full breastfeeding in a southwestern ontario community:
      assessments at 1 week and at 6 months postpartum.
AB  - Factors associated with full breastfeeding (FBF) at 1 week and at 6 months
      postpartum were examined in a cohort of 856 mother-infant dyads. Questionnaires
      were mailed at 4 time points over the first 6 months postpartum. At 1 week, 68%
      of infants were FBF; at 6 months, 23% were FBF. Factors significantly associated
      with FBF at 1 week were hospital of delivery, residing with a smoker, maternal
      shiftwork during pregnancy, and having no prior breast-feeding experience. Cox
      proportional hazards regression analysis showed that residing with a smoker,
      having consumed caffeine during pregnancy, reporting elevated maternal trait
      anxiety at 1 week postpartum, having been employed full-time outside the home
      prior to delivery, and having received anesthesia/analgesia during labor/delivery
      were associated with earlier cessation of FBF, whereas not having previous
      breastfeeding experience predicted its continuation. Although most mothers are
      breastfeeding early on, a number of factors adversely affect its successful
      continuation.

PMID- 16885490
TI  - Mood states and milk output in lactating mothers of preterm and term infants.
AB  - The purpose of this study is to compare psychological distress via both negative
      and positive mood states between 2 different groups of lactating mothers during
      the first 6 weeks postpartum with a large sample. Mood states were measured using
      the Multiple Affect Adjective Check List-Revised by a convenience sample of newly
      delivered mothers from 4 tertiary care units in Illinois. Preterm mothers'
      negative mood states of anxiety, depression, hostility, and dysphoria were
      significantly greater than those reported for term mothers. For the positive mood
      states of positive affect and PASS (positive affect + sensation seeking), preterm
      mothers had significantly lower scores than term mothers; there were no
      differences for the positive mood state, Sensation Seeking. Maternal perceived
      mood states had no apparent effect upon lactation as measured by milk volume
      produced. Further study is warranted to determine what factors influence milk
      output in mothers of preterm and term infants who are at risk for lactation
      failure.

PMID- 16885491
TI  - Effect of intervention to improve breastfeeding technique on the frequency of
      exclusive breastfeeding and lactation-related problems.
AB  - This randomized clinical trial compared frequencies of exclusive breastfeeding
      and lactation-related problems during the first 30 days among 74 mothers who
      received a 30-minute counseling session on breastfeeding technique in the
      maternity ward, and 137 controls. The frequency of exclusive breastfeeding among
      mothers who had received intervention was similar to controls by 7 days (79.7% vs
      82.5%, respectively) and 30 days (60.8% vs 53.3%). There was no difference
      between groups in the frequency of sore nipples at 7 and 30 days, in breast
      engorgement and mastitis, and in the quality of breastfeeding technique at 30
      days. Therefore, a single intervention at maternity was not sufficient to improve
      breastfeeding technique, increase exclusive breastfeeding rates, and reduce the
      incidence of breastfeeding problems during the first month.

PMID- 16885492
TI  - A description of lactation counseling practices that are used with obese mothers.
AB  - Maternal overweight and obesity are associated with failure to initiate
      breastfeeding successfully and to sustain breastfeeding adequately. The purpose
      of this study was to describe how health care providers counsel obese mothers
      about breastfeeding. The authors surveyed (by telephone or in-person interview)
      health care providers who counsel mothers about breastfeeding in rural upstate
      New York (n = 89). They also surveyed lactation consultants (n = 31) from New
      York, New Jersey, Florida, Nebraska, California, and Texas by e-mail. The authors
      found that the majority of health care providers surveyed neither believed that
      there was a difference in the success rate between obese mothers and normal
      weight mothers nor advised obese mothers differently about breastfeeding. Given
      the excess risk for premature lactation failure among obese women, these findings
      suggest that those who care for such women need to be made aware of this risk so
      that they can develop and provide appropriate services.

PMID- 16885493
TI  - Mandibular asymmetry and breastfeeding problems: experience from 11 cases.
AB  - The authors review the experiences of 11 mother-infant pairs who had
      breastfeeding problems related to the infants' mandibular asymmetry. Lower jaw
      asymmetry is an early identifiable sign of torticollis, and a possible
      contributor to latch difficulties, nipple pain, and poor milk transfer.
      Pediatricians and lactation consultants should look for signs of lower jaw
      asymmetry combined with a preference for turning the head to one side in newborns
      who present with breastfeeding difficulties. By recognizing these anatomic
      irregularities early in the course of breastfeeding, pediatric health care
      providers will be able to treat breastfeeding problems promptly and proactively.
      They will be able to avoid unnecessary hospital admissions for dehydration
      symptoms or a septic workup and will intervene quickly with the recommendation of
      breast pumping and complementary feeding if milk transfer is not occurring.

PMID- 16885495
TI  - Recurrent plugged ducts.

PMID- 16885494
TI  - Quality control of banked milk in Brasilia, Brazil.
AB  - The authors studied quality control procedures at human milk banks and
      nutritional profiles of 909 milk samples (from 195 donors, aged 15 to 45 years)
      from banked human milk (BHM) in Brasilia, Brazil. Number of donations per donor
      ranged from 1 to > 10 that consisted mostly of mature milk (90.9%) with a mean
      total energy of 529 +/- 85 kcal/L and a mean total lipid of 22.7 g/L +/- 13.2.
      Microbiological quality (titrable acidity-Dornic, degrees D) was suitable for
      infant feeding in 99.2% of samples (< 8 degrees D), ranging from 2 degrees D to 8
      degrees D (mean 4.8 +/- 1.4 degrees D). Most BHM (98.1%) samples were dispensed
      to inpatient infants (1-7 days) diagnosed with respiratory distress (30.1%),
      prematurity (20.7%), metabolic distress (16.0%), jaundice (14.4%), bacterial
      infection (6.0%), pneumonia (3.3%), congenital cardiac distress (2.2%), or other
      conditions (6.2%). Well-motivated mothers and trained staff are serving and
      sustaining an important life-saving network with long-lasting impact on public
      health.

PMID- 16885496
TI  - Breastfeeding with diabetes: yes you can!

PMID- 16885500
TI  - Signal transduction induced by apoptotic cells inhibits HIV transcription in
      monocytes/macrophages.
AB  - The primary targets of HIV are CD4(+) T cells and macrophages. HIV infection is
      associated with an increase in apoptosis of infected and uninfected CD4(+) T
      cells, and these infected cells undergo apoptosis and produce HIV virions with
      phosphatidylserine (PS) on their surface. During phagocytosis of apoptotic cells,
      macrophages, using an array of receptors, are able to perceive various surface
      changes on apoptotic cells. The engagement of phagocytic receptors by ligands on
      the apoptotic cell surface results in the activation of signaling cascades, which
      facilitate engulfment. In this study, we examined how PS associated with virions
      and apoptotic cells influences HIV replication. We demonstrate that virus
      associated PS is required for HIV infection of macrophages at a step prior to
      integration but following strong-stop, indicating that PS-initiated signals alter
      the establishment of HIV provirus. Conversely, apoptotic cells inhibited HIV
      transcription in infected macrophages, although this ability to suppress
      transcription was independent of PS. Furthermore, we show that ELMO, a key
      signaling molecule that participates in the phagocytosis of apoptotic cells,
      inhibited HIV transcription; however, knocking down endogenous ELMO expression in
      infected U937 cells rescued HIV transcription when these cells were coincubated
      with apoptotic targets. Taken together, these data show that apoptotic cells and
      the signals, which they initiate upon recognition by macrophages, influence the
      successful establishment of HIV infection and provirus transcription.

PMID- 16885501
TI  - Granulocyte macrophage colony-stimulating factor enhances retinoic acid-induced
      gene expression.
AB  - We reported previously that treatment of human myeloblastic leukemia ML-1 cells
      with all-trans retinoic acid (ATRA) in combination with GM-CSF enhances the
      granulocytic differentiation, which is induced only slightly by ATRA alone. To
      investigate the mechanism underlying this differentiation and the synergistic
      effect of ATRA and GM-CSF, we used cDNA microarray to examine gene expression
      profiles of ML-1 cells treated with ATRA and/or GM-CSF. We identified 22 up
      regulated genes in ML-1 cells treated with both reagents and examined the
      expression of these genes in cells treated with ATRA and/or GM-CSF by Northern
      blot analysis. Comparison of cells treated with both reagents and cells treated
      with ATRA or GM-CSF alone revealed that expression of nine of the 19 genes was
      induced synergistically by combined treatment with ATRA and GM-CSF. Expression of
      most of these genes was increased only slightly by ATRA alone, and this induction
      was enhanced by the addition of GM-CSF. These results indicate that GM-CSF
      enhances ATRA-induced gene expression. Moreover, studies with inhibitors of
      signaling molecules suggested that activation of JAK2 is associated with the
      synergistic induction of several genes by ATRA and GM-CSF. JAK2 inhibitor
      suppressed induction of NBT-reducing activity in ML-1 cells treated with both
      reagents. It is likely that the enhancer effect of GM-CSF on ATRA-induced gene
      expression leads to the differentiation induced synergistically by ATRA combined
      with GM-CSF. Further studies of the mechanism underlying this effect may identify
      better approaches for the treatment of RA-insensitive leukemia.

PMID- 16885502
TI  - Cellular reprogramming by gram-positive bacterial components: a review.
AB  - LPS tolerance has been the focus of extensive scientific and clinical research
      over the last several decades in an attempt to elucidate the sequence of changes
      that occur at a molecular level in tolerized cells. Tolerance to components of
      gram-positive bacterial cell walls such as bacterial lipoprotein and lipoteichoic
      acid is a much lesser studied, although equally important, phenomenon. This
      review will focus on cellular reprogramming by gram-positive bacterial components
      and examines the alterations in cell surface receptor expression, changes in
      intracellular signaling, gene expression and cytokine production, and the
      phenomenon of cross-tolerance.

PMID- 16885503
TI  - 5-Hydroxyeicosatetraenoic acid is a key intermediate of the arachidonate
      dependent protective signaling in monocytes/macrophages exposed to peroxynitrite.
AB  - Endogenous generation of arachidonic acid via selective activation of cytosolic
      phospholipase A(2) has been implicated in the mechanism of monocytes/macrophage
      survival in the presence of peroxynitrite. In particular, the lipid messenger was
      shown to prevent the otherwise rapid onset of a mitochondrial permeability
      transition (MPT)-dependent necrosis by causing the mitochondrial translocation of
      protein kinase Calpha (PKCalpha) and the ensuing cytosolic accumulation of the
      Bcl-2-antagonist of cell death (Bad), an event promoting the anti-MPT function of
      Bcl-2 (or Bcl-X(L)). Here, we show that the effects on PKCalpha are not mediated
      directly by arachidonate but rather, by downstream products of the enzyme 5
      lipoxygenase (5-LO). Peroxynitrite elicited the nuclear membrane translocation of
      5-LO and enhanced its enzymatic activity via a mechanism sensitive to low
      concentrations of inhibitors of 5-LO or the 5-LO-activating protein, as well as
      to genetic depletion of the latter enzyme. Inhibition of 5-LO activity was
      invariably associated with the cytosolic localization of PKCalpha, the
      mitochondrial accumulation of Bad, and a rapid MPT-dependent necrosis. All these
      events were prevented by nanomolar concentrations of the 5-LO product 5
      hydroxyeicosatetraenoic acid.

PMID- 16885504
TI  - Comparative inflammatory properties of staphylococcal superantigenic enterotoxins
      SEA and SEG: implications for septic shock.
AB  - The severity of Staphylococcus aureus sepsis is positively associated with
      staphylococcal enterotoxin A (SEA) and negatively associated with the enterotoxin
      gene cluster (egc), which encodes five staphylococcal enterotoxins. We postulated
      that the variable, clinical severity of S. aureus sepsis might be a result of
      differences in the inflammatory properties of staphylococcal superantigens. We
      therefore compared the inflammatory properties of SEA with those of
      staphylococcal enterotoxin G (SEG), a member of the five egc superantigens. We
      found that SEA and SEG had similar superantigenic properties, as they induced
      CD69 expression on T lymphocytes and selective expansion of Vbeta subpopulations.
      Contrary to SEG, however, SEA induced a strong proinflammatory/Th1 response,
      including TNF-alpha and MIP-1alpha production. These results suggest that the
      association of SEA with the severity of S. aureus septic shock, characterized by
      a deleterious, inflammatory cascade, may be explained partly by the specific
      proinflammatory properties of this superantigen.

PMID- 16885505
TI  - T cells traffic from brain to cervical lymph nodes via the cribroid plate and the
      nasal mucosa.
AB  - Although drainage pathways of soluble antigens from brain to cervical lymph nodes
      have been well established, there is no direct evidence for similar routes of
      leukocytes leaving the central nervous system. We developed a protocol allowing
      the cross-sectioning of an entire head-neck preparation while preserving the
      signal of the GFP. We monitored how GFP-expressing CD4 T lymphocytes injected
      into the entorhinal cortex after lesion or the lateral ventricle of unlesioned
      C57/bl6 mice reach cervical lymph nodes. Irrespective of the injection site, we
      demonstrate their passage through the cribroid plate, appearance in the nasal
      mucosa, and specific accumulation in one of the cervical lymph nodes.

PMID- 16885506
TI  - Polymorphism in Sp1 recognition site of the EGF receptor gene promoter and risk
      of glioblastoma.
AB  - We investigated two polymorphisms of the epidermal growth factor receptor
      promoter as potential risk factors and prognostic markers for glioblastoma. The 
      216T allele (which results in a 30% higher activity) was more frequent in the
      patients compared with the control population (224/376 = 59.6% vs 165/352 =
      46.8%; p = 0.0006) corresponding to an odd ratio of 1.67 (1.24; 2.25). A modest
      difference in median survival was also associated with the TT genotype.

PMID- 16885507
TI  - Predicting willingness to engage in unsafe sex and intention to perform sexual
      protective behaviors among adolescents.
AB  - This article examines the sociocognitive processes contributing to intention to
      use contraception and willingness to engage in unsafe sex, using extended
      versions of the theory of planned behavior (TPB) and the Prototype/Willingness
      model (Gibbons & Gerrard, 1995, 1997). Data were obtained from a questionnaire
      delivered to all the pupils in ninth grade (N = 196) at three schools in Oslo.
      Hierarchical multiple regression analysis was used to predict intention and
      willingness. The results showed that subjective norm was the most important
      predictor of intentions for girls, whereas moral norm was most important for
      boys' intentions and willingness. Prototypes were the most important predictor
      for girls' willingness. Implications of the findings are discussed.

PMID- 16885508
TI  - Do the transtheoretical processes of change predict transitions in stages of
      change for fruit intake?
AB  - In a longitudinal study, it is examined whether the transtheoretical processes of
      change do predict stage transitions in fruit intake. A random sample of an
      existing Internet research panel resulted in a cohort of 735 adults, who were
      examined three times with electronic questionnaires assessing stages of change,
      processes of change, and fruit intake. Cross-sectional differences were found for
      the processes of change between precontemplation and all further stages.
      Experiential as well as behavioral processes increased from precontemplation to
      action with similar patterns. Both experiential and behavioral processes
      predicted forward transition out of precontemplation and forward transition into
      action, whereas only behavioral processes predicted forward transition out of
      contemplation. The results indicate that the transtheoretical processes of change
      predict stage transitions for fruit intake, but that the pattern of relevant
      processes for fruit intake is not as straightforward as outlined by the
      transtheoretical model of behavior change.

PMID- 16885509
TI  - Understanding facilitators of and barriers to health promotion practice.
AB  - The health promotion best practices literature is imbued with hope for knowledge
      mobilization, enhanced practice, and improved population health. Given
      constrained medical care systems, health promotion is key to reducing the
      significant burden of chronic disease. However, we have seen little evidence of
      change. This article investigates facilitators of, and barriers to, three stages
      of health promotion practice in public health organizations, interagency
      coalitions, and volunteer committees. The article focuses not on what works but
      why it does or does not, drawing on five case studies within the Canadian Heart
      Health Initiative. Results indicate that the presence or absence of appropriately
      committed and/or skilled people, funds and/or resources, and priority and/or
      interest are the most common factors affecting all stages of health promotion
      practice. The article extends the literature on internal and external factors
      affecting health promotion and highlights strategic influences to consider in
      support of effective health promotion practice.

PMID- 16885510
TI  - "Una mujer trabaja doble aqui": Vignette-based focus groups on stress and work
      for Latina blue-collar women in eastern North Carolina.
AB  - Latina women are a growing percentage of the working population, and very little
      is known about their health needs and interests. The purpose of this article is
      to share qualitative research results gathered from Latina women with a
      particular focus on exploring stress and health. This project was a substudy of
      Health Works in the Community, a 5-year CDC-funded multiple risk-factor reduction
      trial using participatory action research approaches to address smoking, healthy
      eating, stress, and physical activity among blue-collar women from 12
      manufacturing work sites in rural, eastern North Carolina. Five focus groups were
      conducted with trained, bilingual facilitators using a vignette-based moderator
      guide that appeared particularly effective with this population. Results from the
      focus groups are used to make recommendations for future research with Latinas
      and for developing effective work-site-based interventions to address issues of
      stress and health within this population.

PMID- 16885511
TI  - The health-e-AME faith-based physical activity initiative: Description and
      baseline findings.
AB  - This article provides an overview of the development, implementation, and
      baseline findings from a statewide faith-based physical activity (PA) initiative.
      The 3-year program is training African Methodist Episcopal volunteers across
      South Carolina to implement programs to increase PA in their congregations. To
      date, 98 churches have been trained. Interviews done with a random sample (n =
      39) indicated that 54% are implementing at least one PA program. The baseline
      telephone survey (N = 571) estimates that 27.8% of the population is regularly
      active, 54.9% underactive, and 17.3% sedentary. Baseline rates of regular PA were
      higher in those who were younger, healthier, and nonsmokers. Challenges to date
      have included obtaining rosters and implementing a large-scale program with
      limited resources. Interest in the program has been strong and supported by
      church leaders. Current efforts are on training additional churches and working
      with those already trained to support sustainability.

PMID- 16885512
TI  - Development and implementation of a food store-based intervention to improve diet
      in the Republic of the Marshall Islands.
AB  - Effective approaches for the prevention and reduction of obesity and obesity
      related chronic diseases are urgently needed. Food store-centered programs
      represent one approach that may be both effective and sustainable. The authors
      developed a food store-based intervention in the Marshall Islands using
      qualitative and quantitative formative research methods, including a store usage
      survey (n = 184) and in-depth interviews with large-store managers (n = 13),
      small-store managers (n = 7), customers (n = 10), and community leaders (n = 4).
      This process was followed up by development and piloting of specific intervention
      components and workshops to finalize materials. The final intervention combined
      mass media (newspaper articles, video, radio announcements) and in-store
      components (shelf labels, cooking demonstrations, posters, recipe cards) and had
      high store-owner support and participation. High levels of exposure to the
      intervention were achieved during the 10-week period of implementation. This
      model for developing food store-based interventions is applicable to other
      settings.

PMID- 16885513
TI  - Distraction forces on repaired bucket-handle lesions in the medial meniscus.
AB  - BACKGROUND: Numerous studies have investigated the biomechanical properties of
      meniscal repair techniques. One of the most commonly discussed parameters is the
      failure load in the axis of insertion, although little is known about the
      distraction forces actually occurring at repaired bucket-handle lesions.
      HYPOTHESIS: There are clinically relevant distraction forces on repaired meniscus
      bucket-handle lesions. STUDY DESIGN: Controlled laboratory study. METHODS:
      Meniscus bucket-handle lesions were created and repaired in human cadaveric knees
      with a vertical suture made from a braided steel wire. A small-sized load sensor
      was connected to the wire at the periphery of the meniscus. The distraction
      forces acting on the lesion were measured at different knee joint angles (0
      degrees -120 degrees of flexion) with internal and external rotation and with and
      without weight loading. Forces in excess of 10 N were considered to have clinical
      relevance. RESULTS: Mean forces on the meniscus repair ranged from 1.64 to 4.72
      N. Irrespective of the modalities (ie, different flexion angles, weight load,
      direction of rotation), it was found that the forces were well below the cutoff
      value of 10 N (P < .01). Increasing flexion angles generally did not cause an
      increase in distraction forces. CONCLUSION: The data suggest that distraction
      forces are not the primary factor in the mechanical stability of meniscal repair.
      It must therefore be assumed that other factors such as shear forces are of
      greater significance. CLINICAL RELEVANCE: The results may help to validate the
      biomechanical properties of different meniscal repair techniques.

PMID- 16885514
TI  - In vivo kinematics of the knee after anterior cruciate ligament reconstruction: a
      clinical and functional evaluation.
AB  - BACKGROUND: Recent follow-up studies have reported a high incidence of joint
      degeneration in patients with anterior cruciate ligament reconstruction. Abnormal
      kinematics after anterior cruciate ligament reconstruction have been thought to
      contribute to the degeneration. HYPOTHESIS: Anterior cruciate ligament
      reconstruction, which was designed to restore anterior knee laxity under anterior
      tibial loads, does not reproduce knee kinematics under in vivo physiological
      loading conditions. STUDY DESIGN: Controlled laboratory study. METHODS: Both
      knees of 7 patients with complete unilateral rupture of the anterior cruciate
      ligament were magnetic resonance imaged, and 3D models were constructed from
      these images. The anterior cruciate ligament of the injured knee was
      arthroscopically reconstructed using a bone-patellar tendon-bone autograft. Three
      months after surgery, the kinematics of the intact contralateral and
      reconstructed knees were measured using a dual-orthogonal fluoroscopic system
      while the subjects performed a single-legged weightbearing lunge. The anterior
      laxity of both knees was measured using a KT-1000 arthrometer. RESULTS: The
      anterior laxity of the reconstructed knee as measured with the arthrometer was
      similar to that of the intact contralateral knee. However, under weightbearing
      conditions, there was a statistically significant increase in anterior
      translation of the reconstructed knee compared with the intact knee at full
      extension (approximately 2.9 mm) and 15 degrees (approximately 2.2 mm) of
      flexion. In addition, there was a mean increase in external tibial rotation of
      the anterior cruciate ligament-reconstructed knee beyond 30 degrees of flexion
      (approximately 2 degrees at 30 degrees of flexion), although no statistical
      significance was detected. CONCLUSION: The data demonstrate that although
      anterior laxity was restored during KT-1000 arthrometer testing, anterior
      cruciate ligament reconstruction did not restore normal knee kinematics under
      weightbearing loading conditions. CLINICAL RELEVANCE: Future reconstruction
      techniques should aim to restore function of the knee under physiological loading
      conditions.

PMID- 16885515
TI  - Relationships between calcium and pH in the regulation of the slow
      afterhyperpolarization in cultured rat hippocampal neurons.
AB  - The Ca(2+)-dependent slow afterhyperpolarization (AHP) is an important
      determinant of neuronal excitability. Although it is established that modest
      changes in extracellular pH (pH(o)) modulate the slow AHP, the relative
      contributions of changes in the priming Ca(2+) signal and intracellular pH
      (pH(i)) to this effect remain poorly defined. To gain a better understanding of
      the modulation of the slow AHP by changes in pH(o), we performed simultaneous
      recordings of intracellular free calcium concentration ([Ca(2+)](i)), pH(i), and
      the slow AHP in cultured rat hippocampal neurons coloaded with the Ca(2+)- and pH
      sensitive fluorophores fura-2 and SNARF-5F, respectively, and whole cell patch
      clamped using the perforated patch technique. Decreasing pH(o) from 7.2 to 6.5
      lowered pH(i), reduced the magnitude of depolarization-evoked [Ca(2+)](i)
      transients, and inhibited the subsequent slow AHP; opposite effects were observed
      when pH(o) was increased from 7.2 to 7.5. Although decreases and increases in
      pH(i) (at a constant pH(o)) reduced and augmented, respectively, the slow AHP in
      the absence of marked changes in preceding [Ca(2+)](i) transients, the inhibition
      of the slow AHP by decreases in pH(o) was correlated with low pH(o)-dependent
      reductions in [Ca(2+)](i) transients rather than the decreases in pH(i) that
      accompanied the decreases in pH(o). In contrast, high pH(o)-induced increases in
      the slow AHP were correlated with the accompanying increases in pH(i) rather than
      high pH(o)-dependent increases in [Ca(2+)](i) transients. The results indicate
      that changes in pH(o) modulate the slow AHP in a manner that depends on the
      direction of the pH(o) change and substantiate a role for changes in pH(i) in
      modulating the slow AHP during changes in pH(o).

PMID- 16885516
TI  - Distributed and selective auditory representation of song repertoires in the
      avian song system.
AB  - For many songbirds, the vocal repertoire constitutes acoustically distinct songs
      that are flexibly used in various behavioral contexts. To investigate how these
      different vocalizations are represented in the song neural system, we presented
      multiple song stimuli while performing extracellular recording in nucleus HVC in
      adult male song sparrows Melospiza melodia, a species known for its complex vocal
      repertoire and territorial use of song. We observed robust auditory responses to
      natural song stimuli in both awake and anesthetized animals. Auditory responses
      were selective for multiple songs of the bird's own repertoire (BOR) over
      acoustically modified versions of these stimuli. Selectivity was evident in both
      awake and anesthetized HVC, in contrast to auditory selectivity in zebra finch
      HVC, which is apparent only under anesthesia. Presentation of multiple song
      stimuli at different recording locations demonstrated that stimulus acoustic
      features and local neuronal tuning both contribute to auditory responsiveness.
      HVC auditory responsiveness was broadly distributed and nontopographic. Variance
      in auditory responsiveness was greater among than within HVC recording locations
      in both anesthetized and awake birds, in contrast to the global nature of
      auditory representation within zebra finch HVC. To assess the spatial consistency
      of auditory representation within HVC, we measured the repeatability with which
      ensembles of BOR songs were represented across the nucleus. Auditory response
      ranks to different songs were more consistent across recording locations in awake
      than in anesthetized animals. This spatial reliability of auditory responsiveness
      suggests that sound stimulus acoustic features contribute relatively more to
      auditory responsiveness in awake than in anesthetized animals.

PMID- 16885517
TI  - Temporally precise cortical firing patterns are associated with distinct action
      segments.
AB  - Despite many reports indicating the existence of precise firing sequences in
      cortical activity, serious objections have been raised regarding the statistics
      used to detect them and the relations of these sequences to behavior. We show
      that in behaving monkeys, pairs of spikes from different neurons tend to prefer
      certain time delays when measured in relation to a specific behavior. Single-unit
      activity was recorded from eight microelectrodes inserted into the motor and
      premotor cortices of two monkeys while they were performing continuous
      drawinglike hand movements. Repeated scribbling paths, termed drawing components,
      were extracted by data-mining techniques. The set of the least predictable
      relations between drawing components and pairs of neurons was determined and
      represented by one statistic termed the relations score. The chance probability
      of the relations score was evaluated by teetering the spike times: 1,000
      surrogates were generated by randomly teetering the original time of each spike
      in a small window. In nine of 13 experimental days the precision was better than
      12 ms and, in the best case, spike precision reached 0.5 ms.

PMID- 16885518
TI  - The neuroscience of pleasure. Focus on "Ventral pallidum firing codes hedonic
      reward: when a bad taste turns good".

PMID- 16885519
TI  - An increase in AMPA and a decrease in SK conductance increase burst firing by
      different mechanisms in a model of a dopamine neuron in vivo.
AB  - A stylized, symmetric, compartmental model of a dopamine neuron in vivo shows how
      rate and pattern can be modulated either concurrently or differentially. If two
      or more parameters in the model are varied concurrently, the baseline firing rate
      and the extent of bursting become de-correlated, which provides an explanation
      for the lack of a tight correlation in vivo and is consistent with some
      independence of the mechanisms that generate baseline firing rates versus bursts.
      We hypothesize that most bursts are triggered by a barrage of synaptic input and
      that particularly meaningful stimuli recruit larger numbers of synapses in a more
      synchronous way. An example of concurrent modulation is that increasing the short
      lived AMPA current evokes additional spikes without regard to pattern, producing
      comparable increases in spike frequency and fraction fired in bursts. On the
      other hand, blocking the SK current evokes additional bursts by allowing a
      depolarization that previously produced only a single spike to elicit two or more
      and elongates existing bursts by the same principle, resulting in a greater
      effect on pattern than rate. A probabilistic algorithm for the random insertion
      of spikes into the firing pattern produces a good approximation to the pattern
      changes induced by increasing the AMPA conductance, but not by blocking the SK
      current, consistent with a differential modulation in the latter case.
      Furthermore, blocking SK produced a longer burst with a greater intra-burst
      frequency in response to a simulated meaningful input, suggesting that reduction
      of this current may augment reward-related responses.

PMID- 16885520
TI  - Ventral pallidum firing codes hedonic reward: when a bad taste turns good.
AB  - The ventral pallidum (VP) is a key structure in brain mesocorticolimbic reward
      circuits that mediate "liking" reactions to sensory pleasures. Do firing patterns
      in VP actually code sensory pleasure? Strong evidence for hedonic coding requires
      showing that neural signals track positive increases in sensory pleasure or even
      reversals from bad to good. A useful test is the salt alliesthesia of
      physiological sodium depletion that makes even aversively intense NaCl taste
      become palatable and "liked." We compared VP neural firing activity in rats
      during aversive "disliking" reactions elicited by a noxiously intense NaCl taste
      (triple-seawater 1.5 M concentration) in normal homeostatic state versus in a
      physiological salt appetite state that made the same NaCl taste palatable and
      elicit positive "liking" reactions. We also compared firing elicited by palatable
      sucrose taste, which always elicited "liking" reactions in both states. A
      dramatic doubling in the amplitude of VP neural firing peaks to NaCl was caused
      by salt appetite that matched the affective switch from aversive ("disliking") to
      positive hedonic ("liking") reactions. By contrast, VP neural activity to "liked"
      sucrose taste was always high and never altered. In summary, VP firing activity
      selectively tracks the hedonic values of tastes, even across hedonic reversals
      caused by physiological changes. Our data provide the strongest evidence yet for
      neural hedonic coding of natural sensory pleasures and suggest, by extension, how
      abnormalities in VP firing patterns might contribute to clinical hedonic
      dysfunctions.

PMID- 16885522
TI  - Involvement of peripheral purinoceptors in sympathetic modulation of capsaicin
      induced sensitization of primary afferent fibers.
AB  - Purinoceptors are distributed in primary afferent terminals, where transmission
      of nociceptive information is modulated by these receptors. In the present study,
      we evaluated whether the activation or blockade of purinoceptors of subtypes P2X
      and P2Y in the periphery affected the sensitization of primary afferents induced
      by intradermal injection of capsaicin (CAP) and examined their role in
      sympathetic modulation of sensitization of primary nociceptive afferents.
      Afferent activity was recorded from single Adelta- and C-primary afferent fibers
      in the tibial nerve in anesthetized rats. Peripheral pretreatment with alpha,beta
      methylene adenosine 5'-triphosphate (alpha,beta-meATP), a P2X-selective receptor
      agonist, could potentiate the CAP-induced enhancement of responses of Adelta- and
      C-primary afferent nociceptive fibers to mechanical stimuli in sympathetically
      intact rats. After sympathetic denervation, the enhanced responses of both Adelta
      and C-fibers after CAP injection were dramatically reduced. However, this
      reduction could be restored when P2X receptors were activated by alpha,beta
      meATP. A blockade of P2X receptors by pyridoxalphosphate-6-azophenyl-2',4'
      disulfonic acid could significantly reduce the CAP-induced sensitization of
      Adelta- and C-fibers. Pretreatment with uridine 5'-triphosphate, a P2Y-selective
      receptor agonist, did not significantly affect or restore the CAP-induced
      sensitization of Adelta- and C-fibers under sympathetically intact or
      sympathectomized conditions. Our study supports the view that ATP plays a role in
      modulation of primary afferent nociceptor sensitivity mainly by P2X receptors.
      Combined with our previous study, our data also provide further evidence that the
      sensitization of primary afferent nociceptors is subject to sympathetic
      modulation by activation of P2X as well as alpha(1)-adrenergic receptors.

PMID- 16885521
TI  - Incomplete suppression of distractor-related activity in the frontal eye field
      results in curved saccades.
AB  - Saccades in the presence of distractors show significant trajectory curvature.
      Based on previous work in the superior colliculus (SC), we speculated that
      curvature arises when a movement is initiated before competition between the
      target and distractor goals has been fully resolved. To test this hypothesis, we
      recorded frontal eye field (FEF) activity for curved and straight saccades in
      search. In contrast to the SC, activity in FEF is normally poorly correlated with
      saccade dynamics. However, the FEF, like the SC, is involved in target selection.
      Thus if curvature is caused by incomplete target selection, we expect to see its
      neural correlates in the FEF. We found that saccades that curve toward a
      distractor are accompanied by an increase in perisaccadic activity of FEF neurons
      coding the distractor location, and saccades that curve away are accompanied by a
      decrease in activity. In contrast, for FEF neurons coding the target location,
      there is no significant difference in activity between curved and straight
      saccades. To establish that the distractor-related activity is causally related
      to saccade curvature, we applied microstimulation to sites in the FEF before
      saccades to targets presented without distractors. The stimulation was
      subthreshold for evoking saccades and the temporal structure of the stimulation
      train resembled the activity recorded for curved saccades. The resulting
      movements curved toward the location coded by the stimulation site. These results
      support the idea that saccade curvature results from incomplete suppression of
      distractor-related activity during target selection.

PMID- 16885523
TI  - Endogenous activation of adenosine A(1) receptors accelerates ischemic
      suppression of spontaneous electrocortical activity.
AB  - Cerebral ischemia induces a rapid suppression of spontaneous brain rhythms prior
      to major alterations in ionic homeostasis. It was found in vitro during ischemia
      that the rapidly formed adenosine, resulting from the intracellular breakdown of
      ATP, may inhibit synaptic transmission via the A(1) receptor subtype. The link
      between endogenous A(1) receptor activation during ischemia and the suppression
      of spontaneous electrocortical activity has not yet been established in the
      intact brain. The aim of this study was to investigate in vivo the effects of
      A(1) receptor antagonism by 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) on the
      time to electrocortical suppression during global cerebral ischemia. Adult male
      Wistar rats under chloral hydrate anesthesia were subjected to 1-min transient
      "four-vessel occlusion" ischemic episodes, separated by 20-min reperfusion. The
      rats were injected intraperitoneally with either 1.25 mg/kg DPCPX dissolved in 2
      ml/kg dimethyl sulfoxide (DMSO) or the same volume of DMSO alone, 15 min before
      the third ischemic episode. Time to electrocortical suppression was estimated
      based on the decay of the root mean square of two-channel electrocorticographic
      recordings. During the first two ischemic episodes, electrocortical suppression
      appeared after approximately 12 s in both groups. After DMSO administration,
      ischemic suppression remained unchanged. After DPCPX administration, the time to
      electrocortical suppression was increased by approximately 10 s, and bursts of
      activity were recorded during the entire ischemia. These effects disappeared
      within 15 h after DPCPX administration. Our data provide evidence that during
      cerebral ischemia endogenous activation of A(1) receptors accelerates the
      electrical "shut-down" of the whole brain.

PMID- 16885524
TI  - Dopamine D(2) receptor modulation of K(+) channel activity regulates excitability
      of nucleus accumbens neurons at different membrane potentials.
AB  - The nucleus accumbens (NAc) is a forebrain area in the mesocorticolimbic dopamine
      (DA) system that regulates many aspects of drug addiction. Neuronal activity in
      the NAc is modulated by different subtypes of DA receptors. Although DA signaling
      has received considerable attention, the mechanisms underlying D(2)-class
      receptor (D(2)R) modulation of firing in medium spiny neurons (MSNs) localized
      within the NAc remain ambiguous. In the present study, we performed whole cell
      current-clamp recordings in rat brain slices to determine whether and how D(2)R
      modulation of K(+) channel activity regulates the intrinsic excitability of NAc
      neurons in the core region. D(2)R stimulation by quinpirole or DA significantly
      and dose-dependently decreased evoked Na(+) spikes. This D(2)R effect on
      inhibiting evoked firing was abolished by antagonism of D(2)Rs, reversed by
      blockade of voltage-sensitive, slowly inactivating A-type K(+) currents (I(As)),
      or eliminated by holding membrane potentials at levels in which I(As) was
      inactivated. It was also mimicked by inhibition of cAMP-dependent protein kinase
      (PKA) activity, but not phosphatidylinositol-specific phospholipase C (PI-PLC)
      activity. Moreover, D(2)R stimulation also reduced the inward rectification and
      depolarized the resting membrane potentials (RMPs) by decreasing "leak" K(+)
      currents. However, the D(2)R effects on inward rectification and RMP were blocked
      by inhibition of PI-PLC, but not PKA activity. These findings indicate that, with
      facilitated intracellular Ca(2+) release and activation of the
      D(2)R/G(q)/PLC/PIP(2) pathway, the D(2)R-modulated changes in the NAc
      excitability are dynamically regulated and integrated by multiple K(+) currents,
      including but are not limited to I(As), inwardly rectifying K(+) currents
      (I(Kir)), and "leak" currents (I(K-2P)).

PMID- 16885526
TI  - NMDA receptor subtypes at autaptic synapses of cerebellar granule neurons.
AB  - We studied the action potential-evoked autaptic N-methyl-d-aspartate receptor
      mediated excitatory postsynaptic currents (NMDA-EPSCs) using solitary cerebellar
      neurons cultured in microislands from wild-type (+/+), NR2A subunit knockout
      (NR2A-/-), and NR2C subunit knockout (NR2C-/-) mice. The peak amplitude of
      autaptic NMDA-EPSCs increased for all genotypes between days in vitro 8 (DIV8)
      and DIV13. Compared with +/+ cells at DIV13, NR2A-/- cells had smaller and NR2C-/
      cells had larger NMDA-EPSCs. The decay time of these currents were all
      unexpectedly fast, except in NR2A-/- neurons, and showed small but significant
      shortening with development. Comparison of quantal parameters during development
      indicated an increase in quantal content in all genotypes. The synaptic portion
      of NMDA receptors measured using MK-801 blockade was roughly 50% in all genotypes
      at DIV8, and this percentage became slightly larger in NR2A-/- and NR2C-/-
      neurons at DIV12. The NR2B-selective antagonists Conantokin G and CP101,606
      differed in their blocking actions with development, suggesting the presence of
      both heterodimeric NR1/NR2B and heterotrimeric NR1/NR2A/NR2B receptors. The most
      striking result we obtained was the significant increase of NMDA-EPSC peak
      amplitude and charge transfer in NR2C-/- mice. This was mainly the result of an
      increase in quantal size as estimated from miniature NMDA-EPSCs. The expression
      of NR2C subunit containing receptors was supported by the decreased Mg(2+)
      sensitivity of NMDA receptors at DIV13 in +/+ but not in NR2C-/- cells. Thus
      solitary cerebellar granule neurons provide a novel model to investigate the role
      of receptor subtypes in the developmental changes of synaptic NMDA receptors.

PMID- 16885527
TI  - Focus on TGF-beta signalling.

PMID- 16885528
TI  - The structural basis of TGF-beta, bone morphogenetic protein, and activin ligand
      binding.
AB  - The transforming growth factor-beta (TGF-beta) superfamily is a large group of
      structurally related growth factors that play prominent roles in a variety of
      cellular processes. The importance and prevalence of TGF-beta signaling are also
      reflected by the complex network of check points that exist along the signaling
      pathway, including a number of extracellular antagonists and membrane-level
      signaling modulators. Recently, a number of important TGF-beta crystal structures
      have emerged and given us an unprecedented clarity on several aspects of the
      signal transduction process. This review will highlight these latest advances and
      present our current understanding on the mechanisms of specificity and regulation
      on TGF-beta signaling outside the cell.

PMID- 16885525
TI  - A store-operated Ca(2+) influx pathway in the bag cell neurons of Aplysia.
AB  - Although store-operated Ca(2+) influx has been well-studied in nonneuronal cells,
      an understanding of its nature in neurons remains poor. In the bag cell neurons
      of Aplysia californica, prior work has suggested that a Ca(2+) entry pathway can
      be activated by Ca(2+) store depletion. Using fura-based imaging of intracellular
      Ca(2+) in cultured bag cell neurons, we now characterize this pathway as store
      operated Ca(2+) influx. In the absence of extracellular Ca(2+), the endoplasmic
      reticulum Ca(2+)-ATPase inhibitors, cyclopiazonic acid (CPA) or thapsigargin,
      depleted intracellular stores and elevated intracellular free Ca(2+). With the
      subsequent addition of extracellular Ca(2+), a prominent Ca(2+) influx was
      observed. The ryanodine receptor agonist, chloroethylphenol (CEP), also increased
      intracellular Ca(2+) but did not initiate store-operated Ca(2+) influx, despite
      overlap between CEP- and CPA-sensitive stores. Bafilomycin A, a vesicular H(+)
      ATPase inhibitor, liberated intracellular Ca(2+) from acidic stores and
      attenuated subsequent Ca(2+) influx, presumably by replenishing CPA-depleted
      stores. Store-operated Ca(2+) influx was partially blocked by low concentrations
      of La(3+) or BTP2, and strongly inhibited by either 1-[b-[3-(4
      methoxyphenyl)propoxy]-4-methoxyphenethyl]-1H-imidazole (SKF-96365) or a high
      concentration of Ni(2+). Regarding IP(3) receptor blockers, 2-aminoethyldiphenyl
      borate, but not xestospongin C, prevented store-operated Ca(2+) influx. However,
      jasplakinolide, an actin stabilizer reported to inhibit this pathway in smooth
      muscle cell lines, was ineffective. The bag cell neurons initiate reproductive
      behavior through a prolonged afterdischarge associated with intracellular Ca(2+)
      release and neuropeptide secretion. Store-operated Ca(2+) influx may serve to
      replenish stores depleted during the afterdischarge or participate in the release
      of peptide that triggers behavior.

PMID- 16885529
TI  - TGF-beta superfamily members and ovarian follicle development.
AB  - In recent years, exciting progress has been made towards unravelling the complex
      intraovarian control mechanisms that, in concert with systemic signals,
      coordinate the recruitment, selection and growth of follicles from the primordial
      stage through to ovulation and corpus luteum formation. A plethora of growth
      factors, many belonging to the transforming growth factor-beta (TGF-beta )
      superfamily, are expressed by ovarian somatic cells and oocytes in a
      developmental, stage-related manner and function as intraovarian regulators of
      folliculogenesis. Two such factors, bone morphogenetic proteins, BMP-4 and BMP-7,
      are expressed by ovarian stromal cells and/or theca cells and have recently been
      implicated as positive regulators of the primordial-to-primary follicle
      transition. In contrast, evidence indicates a negative role for anti-Mullerian
      hormone (AMH, also known as Mullerian-inhibiting substance) of pre
      granulosa/granulosa cell origin in this key event and subsequent progression to
      the antral stage. Two other TGF-beta superfamily members, growth and
      differentiation factor-9 (GDF-9) and BMP-15 (also known as GDF-9B) are expressed
      in an oocyte-specific manner from a very early stage and play key roles in
      promoting follicle growth beyond the primary stage; mice with null mutations in
      the gdf-9 gene or ewes with inactivating mutations in gdf-9 or bmp-15 genes are
      infertile with follicle development arrested at the primary stage. Studies on
      later stages of follicle development indicate positive roles for granulosa cell
      derived activin, BMP-2, -5 and -6, theca cell-derived BMP-2, -4 and -7 and oocyte
      derived BMP-6 in promoting granulosa cell proliferation, follicle survival and
      prevention of premature luteinization and/or atresia. Concomitantly, activin, TGF
      beta and several BMPs may exert paracrine actions on theca cells to attenuate LH
      dependent androgen production in small to medium-size antral follicles. Dominant
      follicle selection in monovular species may depend on differential FSH
      sensitivity amongst a growing cohort of small antral follicles. Changes in
      intrafollicular activins, GDF-9, AMH and several BMPs may contribute to this
      selection process by modulating both FSH- and IGF-dependent signalling pathways
      in granulosa cells. Activin may also play a positive role in oocyte maturation
      and acquisition of developmental competence. In addition to its endocrine role to
      suppress FSH secretion, increased output of inhibin by the selected dominant
      follicle(s) may upregulate LH-induced androgen secretion that is required to
      sustain a high level of oestradiol secretion during the pre-ovulatory phase.
      Advances in our understanding of intraovarian regulatory mechanisms should
      facilitate the development of new approaches for monitoring and manipulating
      ovarian function and improving fertility in domesticated livestock, endangered
      species and man.

PMID- 16885530
TI  - Pituitary actions of ligands of the TGF-beta family: activins and inhibins.
AB  - Activins, as members of the transforming growth factor-beta superfamily, control
      and orchestrate many physiological processes and are vital for the development,
      growth and functional integrity of most tissues, including the pituitary.
      Activins produced by pituitary cells work in conjunction with central,
      peripheral, and other local factors to influence the function of gonadotropes and
      maintain a normal reproductive axis. Follistatin, also produced by the pituitary,
      acts as a local buffer to bind activin and modulate its bioactivity. On the other
      hand, inhibins of gonadal origin provide an endocrine feedback signal to
      antagonize activin signaling in cells that express the inhibin co-receptor,
      betaglycan, such as gonadotropes. This review highlights the pituitary roles of
      activin and the mechanisms through which these actions are modulated by inhibin
      and follistatin.

PMID- 16885531
TI  - TGF-beta superfamily expression and actions in the endometrium and placenta.
AB  - Transforming growth factor beta (TGFbeta) superfamily members are closely
      associated with tissue remodelling events and reproductive processes. This review
      summarises the current state of knowledge regarding the expression and actions of
      TGFbeta superfamily members in the uterus, during the menstrual cycle and
      establishment of pregnancy. TGFbetas and activin beta subunits are abundantly
      expressed in the endometrium, where roles in preparation events for implantation
      have been delineated, particularly in promoting decidualisation of endometrial
      stroma. These growth factors are also expressed by epithelial glands and secreted
      into uterine fluid, where interactions with preimplantation embryos are
      anticipated. Knockout models and embryo culture experiments implicate activins,
      TGFbetas, nodal and bone morphogenetic proteins (BMPs) in promoting pre- and post
      implantation embryo development. TGFbeta superfamily members may therefore be
      important in the maternal support of embryo development. Following implantation,
      invasion of the decidua by fetal trophoblasts is tightly modulated. Activin
      promotes, whilst TGFbeta and macrophage inhibitory cytokine-1 (MIC-1) inhibit,
      trophoblast migration in vitro, suggesting the relative balance of TGFbeta
      superfamily members participate in modulating the extent of decidual invasion.
      Activins and TGFbetas have similar opposing actions in regulating placental
      hormone production. Inhibins and activins are produced by the placenta throughout
      pregnancy, and have explored as a potential markers in maternal serum for
      pregnancy and placental pathologies, including miscarriage, Down's syndrome and
      pre-eclampsia. Finally, additional roles in immunomodulation at the materno-fetal
      interface, and in endometrial inflammatory events associated with menstruation
      and repair, are discussed.

PMID- 16885532
TI  - All in the family: TGF-beta family action in testis development.
AB  - To achieve and maintain fertility, the adult mammalian testis produces many
      generations of sperm. While testicular integrity is established in the fetus and
      develops further in juvenile life, sperm production does not ensue until much
      later in life, following the onset of puberty. Signals from the transforming
      growth factor-beta superfamily of proteins are vital for governance of testis
      development and spermatogenesis, and this review discusses our current
      understanding of the mechanisms and processes in which they have been implicated
      with a focus on the fetal and juvenile testis.

PMID- 16885533
TI  - Leptin has concentration and stage-dependent effects on embryonic development in
      vitro.
AB  - There is accumulating evidence that leptin may be directly involved in pre
      implantation embryonic development, however, it is unclear whether there is a
      concentration and stage-dependent regulatory pattern. In this study, the addition
      of 10 ng/ml human recombinant leptin to the culture medium significantly
      increased the percentage of two-cell mouse embryos that developed into
      blastocysts and hatched blastocysts, whereas in the presence of 100 ng/ml leptin,
      the development rate was significantly inhibited. The total cell numbers in the
      hatched blastocysts were significantly higher in the presence of 10 ng/ml leptin
      compared with controls and higher concentrations. The differential sensitivity to
      leptin was found to vary among embryos at different stages of development.
      Supplementation of leptin (10 ng/ml) to culture medium at two- to eight-cell
      stages resulted in a consistent stimulatory effect on embryo development. Most
      interestingly, the inhibitory effect of high leptin concentration (100 ng/ml) on
      embryo development was diminished when it was added to the culture medium at the
      eight-cell stage of development. The concentration-dependent regulation pattern
      was confirmed using sheep embryos, under similar conditions although sheep
      embryos appeared to be more sensitive in responding to leptin. Having established
      the effect of exogenous leptin on embryo development, the expression pattern of
      leptin and its receptors were also investigated. Leptin mRNA was not detected in
      mouse two-, four-, eight-cell and blastocyst stage embryos, whereas three
      isoforms of leptin receptor (Ob-Ra, Ob-Rb and Ob-Re) were identified in these
      cells, indicating that leptin is likely to modulate embryo development via a
      paracrine signalling system.

PMID- 16885534
TI  - Nuclear transfer reprogramming does not improve the low developmental potency of
      embryonic stem cells induced by long-term culture.
AB  - Epigenetic states of embryonic stem (ES) cells are easily altered by long-term
      cultivation and lose their developmental potential. To rescue this reduced
      developmental capacity, nuclear transfer (NT) of ES cells was carried out, and
      original ES and ES cells from cloned blastocysts (ntES) cells established after
      NT were compared with in vitro differentiation ability and developmental
      potential by embryoid body formation and tetraploid aggregation respectively. In
      the establishment of ntES cell lines, the oocytes fused with the ES cell were
      activated, and further cultured to cloned blastocysts. When in vitro
      differentiation ability was examined between original and ntES cell lines derived
      from ES cells with extensive passages (ES-ep), the day of appearance of simple
      embryoid body, cystic embryoid body, and spontaneous beating was almost similar.
      The developmental rates of ES-ep cells, that aggregated with tetraploid embryos
      to term, ranged from 3 to 6%. Moreover, the majority of live pups died soon after
      birth. In the ntES cell lines derived from ES-ep cells, developmental rates
      ranged from 0 to 5%. Those pups also died soon after birth, similar to the ES-ep
      derived pups. These results suggest that profound epigenetic modifications of ES
      cells were retained in the re-established cell lines by NT.

PMID- 16885535
TI  - Imprinted gene expression in the rat embryo-fetal axis is altered in response to
      periconceptional maternal low protein diet.
AB  - In our previous study, we have shown that maternal low protein diet (LPD, 9%
      casein vs 18% casein control) fed exclusively during the rat preimplantation
      period (0-4.25 day postcoitum) induced low birth weight, altered postnatal growth
      and hypertension in a gender-specific manner. In this study, we investigated the
      effect of maternal LPD restricted only to the preimplantation period (switched
      diet) or provided throughout gestation on fetal growth and imprinted gene
      expression in blastocyst and fetal stages of development. Male, but not female,
      blastocysts collected from LPD dams displayed a significant reduction (30%) in
      H19 mRNA level. A significant reduction in H19 (9.4%) and Igf2 (10.9%) mRNA was
      also observed in male, but not in female, fetal liver at day 20 postcoitum in
      response to maternal LPD restricted to the preimplantation period. No effect on
      the blastocyst expression of Igf2R was observed in relation to maternal diet. The
      reduction in H19 mRNA expression did not correlate with an observed alteration in
      DNA methylation at the H19 differentially methylated region in fetal liver. In
      contrast, maternal LPD throughout 20 days of gestation did not affect male or
      female H19 and Igf2 imprinted gene expression in fetal liver. Neither LPD nor
      switched diet treatments affected H19 and Igf2 imprinted gene expression in day
      20 placenta. Our findings demonstrate that one contributor to the alteration in
      postnatal growth induced by periconceptional maternal LPD may derive from a
      gender-specific programming of imprinted gene expression originating within the
      preimplantation embryo itself.

PMID- 16885536
TI  - Somatic cell nuclear transfer alters peri-implantation trophoblast
      differentiation in bovine embryos.
AB  - Abnormal placental development limits success in ruminant pregnancies derived
      from somatic cell nuclear transfer (SCNT), due to reduction in placentome number
      and consequently, maternal/fetal exchange. In the primary stages of an epithelial
      chorial association, the maternal/fetal interface is characterized by progressive
      endometrial invasion by specialized trophoblast binucleate/giant cells (TGC). We
      hypothesized that dysfunctional placentation in SCNT pregnancies results from
      aberration in expression of genes known to be necessary for trophoblast
      proliferation (Mash2), differentiation (Hand1), and function (IFN-tau and PAG-9).
      We, therefore, compared the expression of these factors in trophoblast from
      bovine embryos derived from artificial insemination (AI), in vitro fertilization
      (IVF), and SCNT prior to (day 17) and following (day 40 of gestation)
      implantation, as well as TGC densities and function. In preimplantation embryos,
      Mash2 mRNA was more abundant in SCNT embryos compared to AI, while Hand1 was
      highest in AI and IVF relative to SCNT embryos. IFN-tau mRNA abundance did not
      differ among groups. PAG-9 mRNA was undetectable in SCNT embryos, present in IVF
      embryos and highest in AI embryos. In postimplantation pregnancies, SCNT fetal
      cotyledons displayed higher Mash2 and Hand1 than AI and IVF tissues. Allelic
      expression of Mash2 was not different among the groups, which suggests that
      elevated mRNA expression was not due to altered imprinting status of Mash2. The
      day 40 SCNT cotyledons had the fewest number of TGC compared to IVF and AI
      controls. Thus, expression of genes critical to normal placental development is
      altered in SCNT bovine embryos, and this is expected to cause abnormal
      trophoblast differentiation and contribute to pregnancy loss.

PMID- 16885537
TI  - Immunolocalization of the hepatocyte growth factor (HGF) system in the rat ovary
      and the anti-apoptotic effect of HGF in rat ovarian granulosa cells in vitro.
AB  - Hepatocyte growth factor (HGF) regulates granulosa cell (GC) steroidogenesis and
      suppresses apoptosis in non-ovarian cells. The hypothesis was thus developed that
      intraovarian HGF supports folliculogenesis by mediating steroidogenesis and
      suppressing apoptosis. To investigate the latter, the anti-apoptotic actions of
      HGF were tested in GCs and follicles isolated from immature rats. Results showed
      that HGF suppressed apoptosis in GC and follicle cultures as visualized using
      apoptosis indicator dye, YO-PRO-1. Immunohistochemistry was used to investigate
      the distribution of HGF, c-met, and HGF activator (HGFA) protein during
      folliculogenesis in equine chorionic gonadotropin (eCG)-primed rats.
      Immunoreactive HGF content was the greatest in GCs within preantral follicles.
      Following eCG, large antral follicles showed elevated HGF staining in theca and
      interstitial cells when compared with GCs. Intense c-met staining was observed in
      GCs within non-primed small preantral follicles; following eCG, the level of c
      met was diminished in GCs, but increased within theca and interstitial cells.
      Theca, interstitium, and GCs in non-primed and primed ovaries contained HGFA.
      Following eCG, HGFA was more apparent in theca cells and the interstitium when
      compared to that in GCs within large antral follicles. The presence of HGF, c
      met, and HGFA in preantral follicles would potentially enable the anti-apoptotic
      effects of HGF that were observed in vitro to occur in vivo. Advanced
      folliculogenesis led to a change in the cellular distribution of the HGF, c-met,
      and HGFA, suggesting that the ovarian HGF system is hormonally regulated in vivo.

PMID- 16885538
TI  - Naturally suppressed apoptosis prevents follicular atresia and oocyte reserve
      decline in the adult ovary of Lagostomus maximus (Rodentia, Caviomorpha).
AB  - It has been widely accepted that mammalian females are born with a non-renewing,
      finite pool of oocytes that will be continuously cleared by atresia, with only a
      small proportion of them reaching ovulation. Apoptosis regulates this mass germ
      cell death, especially through the balance between pro- and anti-apoptotic
      proteins encoded by the BCL-2 gene family. The caviomorph rodent Lagostomus
      maximus, the South American plains viscacha, displays the highest ovulation rate
      known for a mammal releasing 400-800 eggs per cycle. We tested the hypothesis
      that in L. maximus massive polyovulation is a consequence of reduced apoptosis
      resulting in suppressed follicular atresia. We found that anti-apoptotic BCL-2
      gene is markedly expressed in all kind of follicles from primordial to fully
      mature antral stages in the adult ovary of L. maximus. On the other hand, pro
      apoptotic BAX gene showed weak signals or was undetectable by immunohistochemical
      examination. Western blot against both proteins confirmed immunohistochemical
      results. Screening for DNA fragmentation by TUNEL assay was conspicuously
      negative in ovaries from both pregnant and non-pregnant females. In addition,
      alpha-oestrogen receptor also showed an enhanced expression from primordial stage
      to fully mature antral follicles. Our results show that natural preferential
      expression of BCL-2 and restricted BAX expression greatly suppresses apoptosis in
      the ovary of L. maximus. This prevents the decline of the oocyte reserve by
      abolishing follicular atresia and enables the highest ovulation rate known for a
      mammal, 400-800 or more eggs per cycle.

PMID- 16885539
TI  - Urinary oestradiol and testosterone levels from novel male mice approach values
      sufficient to disrupt early pregnancy in nearby inseminated females.
AB  - Previous research has established that exposure to novel male mice can disrupt
      intrauterine implantation of fertilised ova in inseminated females and that much
      of this effect is mediated by factors in the male urine. The present studies were
      designed to examine whether the steroid content of male urine is sufficient to
      account for this effect. Pregnancy was terminated by exogenous 17beta-oestradiol
      administered intranasally on days 2-4 after insemination in doses as low as 0.14
      microg/day. Enzyme immunoassay indicated that male mouse urine reliably contains
      unconjugated 17beta-oestradiol and testosterone. A small but significant increase
      in the amount of urinary oestradiol was observed in males housed nearby
      previously inseminated females as opposed to those housed in isolation. This
      influence was absent in the sire and absent in novel males when the sire was also
      present. The quantity of active steroids in novel male urine approaches the level
      sufficient to account for the disruption of implantation in nearby inseminated
      females.

PMID- 16885540
TI  - Embryo-induced transcriptome changes in bovine endometrium reveal species
      specific and common molecular markers of uterine receptivity.
AB  - The endometrium plays a central role among the reproductive tissues in the
      context of early embryo-maternal communication and pregnancy. This study
      investigated transcriptome profiles of endometrium samples from day 18 pregnant
      vs non-pregnant heifers to get insight into the molecular mechanisms involved in
      conditioning the endometrium for embryo attachment and implantation. Using a
      combination of subtracted cDNA libraries and cDNA array hybridisation, 109 mRNAs
      with at least twofold higher abundance in endometrium of pregnant animals and 70
      mRNAs with higher levels in the control group were identified. Among the mRNAs
      with higher abundance in pregnant animals, at least 41 are already described as
      induced by interferons. In addition, transcript levels of many new candidate
      genes involved in the regulation of transcription, cell adhesion, modulation of
      the maternal immune system and endometrial remodelling were found to be
      increased. The different expression level was confirmed with real-time PCR for
      nine genes. Localisation of mRNA expression in the endometrium was shown by in
      situ hybridisation for AGRN, LGALS3BP, LGALS9, USP18, PARP12 and BST2. A
      comparison with similar studies in humans, mice, and revealed species-specific
      and common molecular markers of uterine receptivity.

PMID- 16885542
TI  - Cigarette smoke extract enhances oxytocin-induced rhythmic contractions of rat
      and human preterm myometrium.
AB  - Although smoking during pregnancy is a major risk factor for preterm delivery,
      the underlying mechanism by which smoking stimulates uterine contractions is
      still poorly understood. In the present study, we tried to clarify the effects of
      smoking on myometrial contractility induced by oxytocin (OT) using cigarette
      smoke extract (CSE). Myometrial strips, which were taken from the rat on day 16
      of pregnancy, and from human preterm and term delivery groups, were incubated
      overnight with several doses of CSE at 37 degrees C under non-hormonal
      conditions. The uterine contractile sensitivity and activity (force and
      frequency) upon exposure to OT were investigated. Furthermore, the expression
      levels of oxytocin receptor (OTR) mRNA in the myometrial strips were investigated
      by real-time PCR. Contractile sensitivity to OT in the rat CSE (10(-7) pieces/ml)
      group was found to be significantly higher than in the control group (P < 0.05).
      Contractile activity did not differ between the CSE and control groups. The
      expression levels of rat OTR mRNA in the CSE (10(-7) pieces/ml) group were
      significantly higher than in the control group (P < 0.01). Similarly, in preterm
      myometrial strips, the expression levels of human OTR mRNA in the CSE (10(-7)
      pieces/ml) group were significantly higher than in the control group (P < 0.05).
      These findings suggest that CSE directly increases the contractile sensitivity of
      preterm myometrium in response to OT by upregulating the expression of OTR mRNA
      and thereby increases the risk of preterm delivery in women, who smoke during
      pregnancy.

PMID- 16885541
TI  - Dual effect of transforming growth factor beta1 on cell adhesion and invasion in
      human placenta trophoblast cells.
AB  - Transforming growth factor beta (TGFbeta) has been shown to be a multifunctional
      cytokine required for embryonic development and regulation of trophoblast cell
      behaviors. In the present study, a non-transformed cell-line representative of
      normal human trophoblast (NPC) was used to examine the effect of TGFbeta1 on
      trophoblast cell adhesion and invasion. In vitro assay showed that TGFbeta1 could
      significantly promote intercellular adhesion, while inhibiting cell invasion
      across the collagen I-coated filter. Reverse transcription (RT)-PCR and gelatin
      zymography demonstrated that TGFbeta1 evidently repressed the mRNA expression and
      proenzyme production of matrix metalloproteinase (MMP)-9, but exerted no effect
      on mRNA expression and secretion of MMP-2. On the other hand, both the mRNA and
      protein expression of epithelial-cadherin and beta-catenin were obviously
      upregulated by TGFbeta1 in dose-dependent fashion, as revealed by RT-PCR and
      western-blot analysis. What is more, one of the critical TGFbeta signaling
      molecules - Smad2 was notably phosphorylated in TGFbeta1-treated NPC cells. The
      data indicates that cell invasion and adhesion are coordinated processes in human
      trophoblasts and that there exists paracrine regulation on adhesion molecules and
      invasion-associated enzymes in human placenta.

PMID- 16885544
TI  - Images in clinical medicine. Lung carcinoma with anti-Hu paraneoplastic syndrome.

PMID- 16885543
TI  - Changes in endocrine profile and reproductive organs during puberty in the male
      marmoset monkey (Callithrix jacchus).
AB  - Data on pubertal maturation in male marmoset, a model for human reproduction, are
      scant and conflicting. We collected data on novel parameters to characterize
      puberty. Twenty-five marmoset monkeys were assigned to five age groups by weeks
      (wk): 21 (pre-pubertal), 43 (onset of puberty), 52 (fully pubertal), 70 (mature),
      and 116 (fully adult). Serum and intratesticular testosterone and pituitary
      bioactive chorionic gonadotropin (bioCG) were measured. Testicular development
      was assessed by ultrasonography, histology, and flow cytometry. Three consecutive
      blood samples revealed extreme fluctuations in testosterone concentrations,
      suggesting an erratic secretion. Age-related changes in serum testosterone and
      pituitary bioCG concentrations were observed. Intratesticular androgens (ITAs)
      showed high fluctuations within groups at all ages and were high in some animals
      by 21 wk. Unexpectedly, no correlation between pituitary bioCG and serum
      testosterone or ITAs was found, but these parameters significantly correlated
      with testicular weight and volume. These observations were consistent a
      dependence on the testis growth on bioCG. Unfortunately, the low serum levels of
      bioCG were not measurable in this study. At 43 wk, the animals reached puberty.
      At 52 wk of age, animals attained maximum body and epididymal weights and
      qualitatively normal spermatogenesis, but testes continued growing, reaching a
      maximum of all parameters at 70 wk of age, without further major changes at the
      age of 116 wk. It is concluded that (1) gonadal activation is evident at wk 21,
      (2) the male marmoset reaches the pubertal threshold around 43 wk of age, attains
      qualitative parameters at 52 wk, matures further to sexual maturity at 70 wk, and
      (3) serum testosterone and ITAs are highly variable without any identifiable
      correlation with pituitary bioCG.

PMID- 16885545
TI  - Access before approval--a right to take experimental drugs?

PMID- 16885546
TI  - Measles in the United States, 2006.

PMID- 16885547
TI  - No refuge for the ailing.

PMID- 16885548
TI  - Implications of a 2005 measles outbreak in Indiana for sustained elimination of
      measles in the United States.
AB  - BACKGROUND: Measles was declared eliminated from the United States in 2000 but
      remains endemic worldwide. In 2005, a 17-year-old unvaccinated girl who was
      incubating measles returned from Romania, creating the largest documented
      outbreak of measles in the United States since 1996. METHODS: We conducted a case
      series investigation, molecular typing of viral isolates, surveys of rates of
      vaccination coverage, interviews regarding attitudes toward vaccination, and cost
      surveys. RESULTS: Approximately 500 persons attended a gathering with the index
      patient one day after her return home. Approximately 50 lacked evidence of
      measles immunity, of whom 16 (32 percent) acquired measles at the gathering.
      During the six weeks after the gathering, a total of 34 cases of measles were
      confirmed. Of the patients with confirmed measles, 94 percent were unvaccinated,
      88 percent were less than 20 years of age, and 9 percent were hospitalized. Of
      the 28 patients who were 5 to 19 years of age, 71 percent were home-schooled.
      Vaccine failure occurred in two persons. The virus strain was genotype D4, which
      is endemic in Romania. Although containment measures began after 20 persons were
      already infectious, measles remained confined mostly to children whose parents
      had refused to have them vaccinated, primarily out of concern for adverse events
      from the vaccine. Seventy-one percent of patients were from four households.
      Levels of measles-vaccination coverage in Indiana were 92 percent for
      preschoolers and 98 percent for sixth graders. Estimated costs of containing the
      disease were at least 167,685 dollars, including 113,647 dollars at a hospital
      with an infected employee. CONCLUSIONS: This outbreak was caused by the
      importation of measles into a population of children whose parents had refused to
      have them vaccinated because of safety concerns about the vaccine. High
      vaccination levels in the surrounding community and low rates of vaccine failure
      averted an epidemic. Maintenance of high rates of vaccination coverage, including
      improved strategies of communication with persons who refuse vaccination, is
      necessary to prevent future outbreaks and sustain the elimination of measles in
      the United States.

PMID- 16885549
TI  - Activating mutations in the ABCC8 gene in neonatal diabetes mellitus.
AB  - BACKGROUND: The ATP-sensitive potassium (K(ATP)) channel, composed of the beta
      cell proteins sulfonylurea receptor (SUR1) and inward-rectifying potassium
      channel subunit Kir6.2, is a key regulator of insulin release. It is inhibited by
      the binding of adenine nucleotides to subunit Kir6.2, which closes the channel,
      and activated by nucleotide binding or hydrolysis on SUR1, which opens the
      channel. The balance of these opposing actions determines the low open-channel
      probability, P(O), which controls the excitability of pancreatic beta cells. We
      hypothesized that activating mutations in ABCC8, which encodes SUR1, cause
      neonatal diabetes. METHODS: We screened the 39 exons of ABCC8 in 34 patients with
      permanent or transient neonatal diabetes of unknown origin. We assayed the
      electrophysiologic activity of mutant and wild-type K(ATP) channels. RESULTS: We
      identified seven missense mutations in nine patients. Four mutations were
      familial and showed vertical transmission with neonatal and adult-onset diabetes;
      the remaining mutations were not transmitted and not found in more than 300
      patients without diabetes or with early-onset diabetes of similar genetic
      background. Mutant channels in intact cells and in physiologic concentrations of
      magnesium ATP had a markedly higher P(O) than did wild-type channels. These
      overactive channels remained sensitive to sulfonylurea, and treatment with
      sulfonylureas resulted in euglycemia. CONCLUSIONS: Dominant mutations in ABCC8
      accounted for 12 percent of cases of neonatal diabetes in the study group.
      Diabetes results from a newly discovered mechanism whereby the basal magnesium
      nucleotide-dependent stimulatory action of SUR1 on the Kir pore is elevated and
      blockade by sulfonylureas is preserved.

PMID- 16885550
TI  - Switching from insulin to oral sulfonylureas in patients with diabetes due to
      Kir6.2 mutations.
AB  - BACKGROUND: Heterozygous activating mutations in KCNJ11, encoding the Kir6.2
      subunit of the ATP-sensitive potassium (K(ATP)) channel, cause 30 to 58 percent
      of cases of diabetes diagnosed in patients under six months of age. Patients
      present with ketoacidosis or severe hyperglycemia and are treated with insulin.
      Diabetes results from impaired insulin secretion caused by a failure of the beta
      cell K(ATP) channel to close in response to increased intracellular ATP.
      Sulfonylureas close the K(ATP) channel by an ATP-independent route. METHODS: We
      assessed glycemic control in 49 consecutive patients with Kir6.2 mutations who
      received appropriate doses of sulfonylureas and, in smaller subgroups,
      investigated the insulin secretory responses to intravenous and oral glucose, a
      mixed meal, and glucagon. The response of mutant K(ATP) channels to the
      sulfonylurea tolbutamide was assayed in xenopus oocytes. RESULTS: A total of 44
      patients (90 percent) successfully discontinued insulin after receiving
      sulfonylureas. The extent of the tolbutamide blockade of K(ATP) channels in vitro
      reflected the response seen in patients. Glycated hemoglobin levels improved in
      all patients who switched to sulfonylurea therapy (from 8.1 percent before
      treatment to 6.4 percent after 12 weeks of treatment, P<0.001). Improved glycemic
      control was sustained at one year. Sulfonylurea treatment increased insulin
      secretion, which was more highly stimulated by oral glucose or a mixed meal than
      by intravenous glucose. Exogenous glucagon increased insulin secretion only in
      the presence of sulfonylureas. CONCLUSIONS: Sulfonylurea therapy is safe in the
      short term for patients with diabetes caused by KCNJ11 mutations and is probably
      more effective than insulin therapy. This pharmacogenetic response to
      sulfonylureas may result from the closing of mutant K(ATP) channels, thereby
      increasing insulin secretion in response to incretins and glucose metabolism.
      (ClinicalTrials.gov number, NCT00334711 [ClinicalTrials.gov].).

PMID- 16885552
TI  - Chronic venous disease.

PMID- 16885553
TI  - Images in clinical medicine. Salt-and-pepper retinopathy of rubella.

PMID- 16885551
TI  - Validation of a rule for termination of resuscitation in out-of-hospital cardiac
      arrest.
AB  - BACKGROUND: We prospectively evaluated a clinical prediction rule to be used by
      emergency medical technicians (EMTs) trained in the use of an automated external
      defibrillator for the termination of basic life support resuscitative efforts
      during out-of-hospital cardiac arrest. The rule recommends termination when there
      is no return of spontaneous circulation, no shocks are administered, and the
      arrest is not witnessed by emergency medical-services personnel. Otherwise, the
      rule recommends transportation to the hospital, in accordance with routine
      practice. METHODS: The study included 24 emergency medical systems in Ontario,
      Canada. All patients 18 years of age or older who had an arrest of presumed
      cardiac cause and who were treated by EMTs trained in the use of an automated
      external defibrillator were included. The patients were treated according to
      standard guidelines. Characteristics of diagnostic tests for the prediction rule
      were calculated. These characteristics include sensitivity, specificity, and
      positive and negative predictive values. RESULTS: Follow-up data were obtained
      for all 1240 patients. Of 776 patients with cardiac arrest for whom the rule
      recommended termination, 4 survived (0.5 percent). The rule had a specificity of
      90.2 percent for recommending transport of survivors to the emergency department
      and had a positive predictive value for death of 99.5 percent when termination
      was recommended. Implementation of this rule would result in a decrease in the
      rate of transportation from 100 percent of patients to 37.4 percent. The addition
      of other criteria (a response interval greater than eight minutes or a cardiac
      arrest not witnessed by a bystander) would further improve both the specificity
      and positive predictive value of the rule but would result in the transportation
      of a larger proportion of patients. CONCLUSIONS: The use of a clinical prediction
      rule for the termination of resuscitation may help clinicians decide whether to
      terminate basic life support resuscitative efforts in patients having an out-of
      hospital cardiac arrest.

PMID- 16885554
TI  - Clinical problem-solving. A sharp right turn.

PMID- 16885556
TI  - Cardiac resuscitation--when is enough enough?

PMID- 16885555
TI  - ATP-sensitive potassium channels--neonatal diabetes mellitus and beyond.

PMID- 16885557
TI  - Limiting myocardial damage during acute myocardial infarction by inhibiting C
      reactive protein.

PMID- 16885558
TI  - The severe gout of Holy Roman Emperor Charles V.

PMID- 16885559
TI  - Balloon angioplasty or nitinol stents for peripheral-artery disease.

PMID- 16885560
TI  - Shattuck Lecture--medical education.

PMID- 16885562
TI  - Budd-Chiari syndrome and factor V Leiden in a neonate.

PMID- 16885561
TI  - Lineage-specific hematopoietic growth factors.

PMID- 16885563
TI  - COX-2 inhibitors and early failure of free vascular flaps.

PMID- 16885564
TI  - Protein expression profiling identifies cyclophilin A as a molecular target in
      Fhit-mediated tumor suppression.
AB  - Loss of fragile histidine triad (Fhit) expression is often associated with human
      malignancies, and Fhit functions as a tumor suppressor in controlling cell growth
      and apoptosis, although specific signal pathways are still undefined. We have
      used a proteomic approach to define proteins in the Fhit-mediated tumor
      suppression pathway. Because substitution of Tyr(114) (Y114) with phenylalanine
      (Y114F) diminishes Fhit functions, we did protein expression profiling to
      identify proteins differentially expressed in Fhit-negative H1299 lung cancer
      cells infected with wild-type (Ad-FHIT-wt) and Y114 mutant FHIT-expressing (Ad
      FHIT-Y114F) adenoviruses. Among 12 distinct proteins that exhibited 4-fold
      differences in expression on comparison of the two infected cell lysates,
      cyclophilin A, the intracellular reporter of the immunosuppressive drug
      cyclosporine A, showed a remarkably decreased protein level in cells infected
      with Ad-FHIT-wt versus Ad-FHIT-Y114F. Conversely, loss of Fhit expression
      resulted in increased cyclophilin A expression in mouse tissues and cell lines.
      Restoration of Fhit expression led to down-regulated cyclophilin A protein
      expression and subsequently prevented cyclophilin A-induced up-regulation of
      cyclin D1, Cdk4, and resultant cell cycle progression (G(1)-S transition), which
      was independent of Ca(2+)/calmodulin-dependent kinase inhibitor, KN-93.
      Interestingly, Fhit down-modulation of phosphatase activity of calcineurin, which
      controls cyclin D1/Cdk4 activation, was reversed by cyclophilin A treatment in a
      concentration-dependent manner, a reversal that was inhibited by additional
      cyclosporine A treatment. Thus, cyclophilin A is a downstream target in Fhit
      mediated cessation of cell cycle progression at late G(1) phase. Elucidation of
      the protein effectors of Fhit signaling may lead to identification of targets for
      lung cancer therapy.

PMID- 16885565
TI  - The medicinal plant goldenseal is a natural LDL-lowering agent with multiple
      bioactive components and new action mechanisms.
AB  - Our previous studies have identified berberine (BBR), an alkaloid isolated from
      the Chinese herb huanglian, as a unique cholesterol-lowering drug that
      upregulates hepatic low density lipoprotein receptor (LDLR) expression through a
      mechanism of mRNA stabilization. Here, we demonstrate that the root extract of
      goldenseal, a BBR-containing medicinal plant, is highly effective in upregulation
      of liver LDLR expression in HepG2 cells and in reducing plasma cholesterol and
      low density lipoprotein cholesterol (LDL-c) in hyperlipidemic hamsters, with
      greater activities than the pure compound BBR. By conducting bioassay-driven
      semipurifications, we demonstrate that the higher potency of goldenseal is
      achieved through concerted actions of multiple bioactive compounds in addition to
      BBR. We identify canadine (CND) and two other constituents of goldenseal as new
      upregulators of LDLR expression. We further show that the activity of BBR on LDLR
      expression is attenuated by multiple drug resistance-1 (MDR1)-mediated efflux
      from liver cells, whereas CND is resistant to MDR1. This finding defines a
      molecular mechanism for the higher activity of CND than BBR. We also provide
      substantial evidence to show that goldenseal contains natural MDR1 antagonist(s)
      that accentuate the upregulatory effect of BBR on LDLR mRNA expression. These new
      findings identify goldenseal as a natural LDL-c-lowering agent, and our studies
      provide a molecular basis for the mechanisms of action.

PMID- 16885566
TI  - Microarray analysis indicates an important role for FABP5 and putative novel
      FABPs on a Western-type diet.
AB  - Liver parenchymal cells play a dominant role in hepatic metabolism and thereby
      total body cholesterol homeostasis. To gain insight into the specific pathways
      and genes involved in the response of liver parenchymal cells to increased
      dietary lipid levels under atherogenic conditions, changes in parenchymal cell
      gene expression upon feeding a Western-type diet for 0, 2, 4, and 6 weeks were
      determined using microarray analysis in LDL receptor-deficient mice, an
      established atherosclerotic animal model. Using ABI Mouse Genome Survey Arrays,
      we were able to detect 7,507 genes (28% of the total number on an array) that
      were expressed in parenchymal cells isolated from livers of LDL receptor
      deficient mice at every time point investigated. Time-dependent gene expression
      profiling identified fatty acid binding protein 5 (FABP5) and four novel FABP5
      like transcripts located on chromosomes 2, 8, and 18 as important proteins in the
      primary response of liver parenchymal cells to Western-type diet feeding, because
      their expression was 16- to 22-fold increased within the first 2 weeks on the
      Western-type diet. The rapid substantial increase in gene expression suggests
      that these FABPs may play an important role in the primary protection against the
      cellular toxicity of cholesterol, free fatty acids, and/or lipid oxidants.
      Furthermore, as a secondary response to the Western-type diet, liver parenchymal
      cells of LDL receptor-deficient mice stimulated glycolysis and lipogenesis
      pathways, resulting in a steady, more atherogenic serum lipoprotein profile
      (increased VLDL/LDL).

PMID- 16885568
TI  - India: promoting tobacco via "research".

PMID- 16885567
TI  - Butt clean up campaigns: wolves in sheep's clothing?

PMID- 16885570
TI  - Australia: BAT corporate social irresponsibility.

PMID- 16885569
TI  - UK: familiar smell at the airport.

PMID- 16885571
TI  - Canada: end of the smoking zone.

PMID- 16885572
TI  - Malaysia: camel tourism trick.

PMID- 16885573
TI  - China: athlete runs into trouble.

PMID- 16885574
TI  - Bangladesh: bicycles, not cigarettes.

PMID- 16885575
TI  - USA: advocates keep up pressure at tobacco AGMs.

PMID- 16885576
TI  - Nicotine replacement therapy for long-term smoking cessation: a meta-analysis.
AB  - OBJECTIVE: To assess if the effect of a single treatment episode with nicotine
      replacement therapy (NRT) enhances smoking cessation over many years. DATA
      SOURCES: Meta-analysis of all randomised controlled trials of NRT with final
      follow-up more than one year after the start of treatment. Twelve eligible trials
      were identified, all placebo-controlled, having final follow-ups ranging from 2-8
      years. All had earlier follow-ups at 12 months. They comprised 2408 active and
      2384 placebo treatment participants. DATA SYNTHESIS: The odds ratio (OR) in
      favour of NRT at final follow-up was 1.99 (95% confidence interval (CI) 1.50 to
      2.64). There was no evidence that the effect varied according to length of final
      follow-up (beta = 0.92, p = 0.28) or duration of initial NRT treatment (beta =
      0.99, p > 0.5). The overall relapse rate between the 12 months and final follow
      up was 30.0% (95% CI 23.5% to 37.5%). This rate did not differ between NRT and
      control groups (OR 1.11, 95% CI 0.78 to 1.59), or length of initial NRT
      treatment. There was also no evidence that it varied according to length of final
      follow up. Due to relapse, the overall efficacy of NRT treatment in terms of
      additional ex-smokers declined from 10.7% over and above placebo (6.6% to 14.8%)
      after one year to 7.2% (3.8% to 11.3%) at an average of 4.3 years follow up.
      CONCLUSIONS: The relative efficacy of a single course of NRT remains constant
      over many years. The majority of relapse after 12 months occurs within the first
      or second year and is not detectable thereafter, suggesting that NRT has a
      permanent effect on smoking cessation. However, initial relapse after one year
      has the effect of diminishing the number of ex-smokers that can be ultimately
      attributed to NRT. Results after only 6-12 months of follow-up, as used in
      existing reviews and treatment guidelines, will overestimate the lifetime benefit
      and cost-efficacy of NRT by about 30%. Because the long-term benefit of NRT is
      modest, tobacco dependence treatment might be better viewed as a chronic
      disorder, requiring repeated episodes of treatment.

PMID- 16885577
TI  - Increased reach and effectiveness of a statewide tobacco quitline after the
      addition of access to free nicotine replacement therapy.
AB  - BACKGROUND: Tobacco users receiving behavioural and pharmacological assistance
      are more likely to quit. Although telephone quitlines provide population access
      to counselling, few offer pharmacotherapy. OBJECTIVE: To assess change in
      cessation rates and programme impact after the addition of free nicotine
      replacement therapy (NRT) to statewide quitline services. DESIGN, SETTING,
      PARTICIPANTS: An observational study of cohorts of callers to the Minnesota
      QUITPLAN(SM) Helpline before (n = 380) and after (n = 373) the addition of access
      to free NRT. INTERVENTION: Mailing of NRT (patch or gum) to callers enrolling in
      multi-session counselling. MAIN OUTCOME MEASURE: Thirty-day abstinence six months
      after programme registration. RESULTS: The number of callers increased from 155
      (SD 75) to 679 (180) per month pre-NRT to post-NRT (difference 524, 95%
      confidence interval (CI) 323 to 725). Post-NRT, the proportion of callers
      enrolling in multi-session counselling (23.4% v 90.1%, difference 66.6%, 95% CI
      60.8% to 71.6%) and using pharmacotherapy (46.8% v 86.8%, difference 40.0%, 95%
      CI 31.3% to 47.9%) increased. Thirty-day abstinence at six months increased from
      10.0% pre-NRT to 18.2% post-NRT (difference 8.2%, 95% CI 3.1% to 13.4%). Post-NRT
      the average number of new ex-smokers per month among registrants increased from
      15.5 to 123.6 (difference 108.1, 95% CI 61.1 to 155.0). The cost per quit pre-NRT
      was 1362 dollars (SD 207 dollars). The cost per quit post-NRT was 1934 dollars
      (215 dollars) suggesting a possible increase in cost per quit (difference 572
      dollars, 95% CI -12 dollars to 1157 dollars). CONCLUSION: The addition of free
      NRT to a state quitline is followed by increases in participation and abstinence
      rates resulting in an eightfold increase in programme impact. These findings
      support the addition of access to pharmacological therapy as part of state
      quitline services.

PMID- 16885578
TI  - Parental smoking and children's respiratory health: independent effects of
      prenatal and postnatal exposure.
AB  - OBJECTIVES: Adverse effects have been reported of prenatal and/or postnatal
      passive exposure to smoking on children's health. Uncertainties remain about the
      relative importance of smoking at different periods in the child's life. We
      investigate this in a pooled analysis, on 53,879 children from 12 cross-sectional
      studies--components of the PATY study (Pollution And The Young). METHODS: Effects
      were estimated, within each study, of three exposures: mother smoked during
      pregnancy, parental smoking in the first two years, current parental smoking.
      Outcomes were: wheeze, asthma, "woken by wheeze", bronchitis, nocturnal cough,
      morning cough, "sensitivity to inhaled allergens" and hay fever. Logistic
      regressions were used, controlling for individual risk factors and study area.
      Heterogeneity between study-specific results, and mean effects (allowing for
      heterogeneity) were estimated using meta-analytical tools. RESULTS: There was
      strong evidence linking parental smoking to wheeze, asthma, bronchitis and
      nocturnal cough, with mean odds ratios all around 1.15, with independent effects
      of prenatal and postnatal exposures for most associations. CONCLUSIONS: Adverse
      effects of both pre- and postnatal parental smoking on children's respiratory
      health were confirmed. Asthma was most strongly associated with maternal smoking
      during pregnancy, but postnatal exposure showed independent associations with a
      range of other respiratory symptoms. All tobacco smoke exposure has serious
      consequences for children's respiratory health and needs to be reduced urgently.

PMID- 16885579
TI  - Smoke-free laws and secondhand smoke exposure in US non-smoking adults, 1999
      2002.
AB  - OBJECTIVES: To investigate the relationship between smoke-free law coverage and
      secondhand smoke (SHS) exposure in the United States non-smoking adult
      population. DESIGN: We used data from the 1999-2002 National Health and Nutrition
      Examination Survey, a cross-sectional survey designed to monitor the health and
      nutritional status of the US population. Serum cotinine levels were available for
      5866 non-smoking adults from 57 survey locations. Each location was categorised
      into one of three groups indicating extensive, limited, and no coverage by a
      smoke-free law. MAIN OUTCOME MEASURES: The proportion of adults with SHS
      exposure, defined as having serum cotinine levels > or = 0.05 ng/ml. RESULTS:
      Among non-smoking adults living in counties with extensive smoke-free law
      coverage, 12.5% were exposed to SHS, compared with 35.1% with limited coverage,
      and 45.9% with no law. Adjusting for confounders, men and women residing in
      counties with extensive coverage had 0.10 (95% confidence interval (CI) 0.06 to
      0.16) and 0.19 (95% CI 0.11 to 0.34) times the odds of SHS exposure compared to
      those residing in counties without a smoke-free law. CONCLUSIONS: These results
      support the scientific evidence suggesting that smoke-free laws are an effective
      strategy for reducing SHS exposure.

PMID- 16885580
TI  - What contributed to the major decline in per capita cigarette consumption during
      California's comprehensive tobacco control programme?
AB  - OBJECTIVES: California experienced a notable decline in per capita cigarette
      consumption during its comprehensive tobacco control programme. This study
      examines what proportion of the decline occurred from: (1) fewer ever smokers in
      the population, (2) more ever smokers quitting, and (3) current smokers smoking
      less. DESIGN, SUBJECTS: Per capita cigarette consumption computed from cigarette
      sales and from adult respondents to the large, cross-sectional, population-based
      California Tobacco Surveys of 1990 (n = 24,296), 1996 (n = 18,616) and 2002 (n =
      20,525) were examined for similar trends. MAIN OUTCOME MEASURE: Changes (period
      1: 1990-1996; period 2: 1996-2002) in per capita cigarette consumption from self
      reported survey data were partitioned for the entire population and for
      demographic subgroups into the three components mentioned above. RESULTS: In
      periods 1 and 2, most of the decline in per capita cigarette consumption for the
      population as a whole was from current smokers smoking less followed by a
      reduction in ever smokers. The decline from smokers smoking less was particularly
      evident among young adults (18-29 years) in period 1. While the portion of the
      decline due to quitting in the entire population in period 1 was negligible, in
      period 2 it accounted for 22% of the total per capita decline. The decline from
      quitting in period 2 was mostly observed among women. CONCLUSIONS: Rather than
      near-term benefits from smokers quitting, population health benefits from reduced
      per capita cigarette consumption will likely occur over the longer term from
      fewer people becoming ever smokers, and more less-addicted smokers eventually
      quitting successfully.

PMID- 16885581
TI  - An ethnographic study of tobacco control in hospital settings.
AB  - BACKGROUND: Tobacco control in hospital settings is characterised by a focus on
      protection strategies and an increasing expectation that health practitioners
      provide cessation support to patients. While practitioners claim to have positive
      attitudes toward supporting patient cessation efforts, missed opportunities are
      the practice norm. OBJECTIVE: To study hospital workplace culture relevant to
      tobacco use and control as part of a mixed-methods research project that
      investigated hospital-based registered nurses' integration of cessation
      interventions. DESIGN: The study was conducted at two hospitals situated in
      British Columbia, Canada. Data collection included 135 hours of field work
      including observations of ward activities and designated smoking areas, 85
      unstructured conversations with nurses, and the collection of patient-care
      documents on 16 adult in-patient wards. RESULTS: The findings demonstrate that
      protection strategies (for example, smoking restrictions) were relatively well
      integrated into organisational culture and practice activities but the same was
      not true for cessation strategies. An analysis of resources and documentation
      relevant to tobacco revealed an absence of support for addressing tobacco use and
      cessation. Nurses framed patients' tobacco use as a relational issue, a risk to
      patient safety, and a burden. Furthermore, conversations revealed that nurses
      tended to possess only a vague awareness of nicotine dependence. CONCLUSION:
      Overcoming challenges to extending tobacco control within hospitals could be
      enhanced by emphasising the value of addressing patients' tobacco use, raising
      awareness of nicotine dependence, and improving the availability of resources to
      address addiction issues.

PMID- 16885582
TI  - Tobacco interests or the public interest: 20 years of industry strategies to
      undermine airline smoking restrictions.
AB  - OBJECTIVES: To understand the evolution of 20 years of tobacco industry
      strategies to undermine federal restrictions of smoking on aircraft in the United
      States. DESIGN: We searched and analysed internal tobacco industry records,
      public documents, and other related research. RESULTS: The industry viewed these
      restrictions as a serious threat to the social acceptability of smoking. Its
      initial efforts included covert letter-writing campaigns and lobbying of the
      airline industry, but with the emergence of proposals to ban smoking, the tobacco
      companies engaged in ever increasing efforts to forestall further restrictions.
      Tactics to dominate the public record became especially rigorous. The industry
      launched an aggressive public relations campaign that began with the promotion of
      industry sponsored petition drives and public opinion surveys. Results from
      polling research that produced findings contrary to the industry's position were
      suppressed. In order to demonstrate smoker outrage against a ban, later efforts
      included the sponsorship of smokers' rights and other front groups. Congressional
      allies and industry consultants sought to discredit the science underlying
      proposals to ban smoking and individual tobacco companies conducted their own
      cabin air quality research. Faced with the potential of a ban on all domestic
      flights, the industry sought to intimidate an air carrier and a prominent
      policymaker. Despite the intensification of tactics over time, including
      mobilisation of an army of lobbyists and Congressional allies, the tobacco
      industry was ultimately defeated. CONCLUSIONS: Our longitudinal analysis provides
      insights into how and when the industry changed its plans and provides public
      health advocates with potential counterstrategies.

PMID- 16885583
TI  - The future of tobacco regulation: a response to a proposal for fundamental
      institutional change.
AB  - There is much debate about the future of tobacco regulation. Some have argued
      that to achieve maximum possible reduction in the harm tobacco causes, new
      regulatory models that involve fundamental institutional change must be adopted.
      The tobacco industry will continue to undermine tobacco control, and, so it is
      argued, we must change the way in which it operates if we are to be able to make
      the necessary progress. Such proposals may have an immediate appeal, especially
      for those frustrated that progress in tobacco control is not as rapid as they
      would hope--with all the avoidable loss of life and livelihoods that that entails
      -but they need to be carefully analysed and assessed, and much thought must be
      applied before spending time and resources advocating for them. One such
      proposal, advanced by Borland, involves the establishment of a monopsonistic
      statutory purchasing agency and wholesale distributor of tobacco products.
      Borland argues the relative benefits of such a model as compared to a more
      "conventional" model. On close examination, the benefits of the Borland proposal,
      as compared to the conventional model, appear overstated, and the Borland
      proposal introduces significant regulatory problems. There is still much that can
      be achieved in tobacco regulation through more conventional approaches, and
      within the "existing system". We should be wary of allowing the understandable
      allure of new or radical approaches to distract us from this reality.

PMID- 16885584
TI  - Why not seek clever regulation? A reply to Liberman.

PMID- 16885585
TI  - Clean cut cigarettes: fictitious launch foreshadows actual tobacco industry
      strategy.
AB  - A fictitious cigarette brand, "launched" at the 11th World Conference on Tobacco
      or Health, appears to have been adopted by Philip Morris.

PMID- 16885586
TI  - Time for a tobacco and nicotine regulatory authority for France.

PMID- 16885587
TI  - Cigarette taxes and prices in Spain: government and industry initiatives.

PMID- 16885589
TI  - The IF of IJMR is on the rise.

PMID- 16885590
TI  - Microbicide development: new challenges.

PMID- 16885591
TI  - Data protection issues in India.

PMID- 16885592
TI  - Is there a change in seroepidemiology of hepatitis A infection in India?

PMID- 16885593
TI  - Chlamydia trachomatis & infertility.

PMID- 16885594
TI  - Smear microscopy to diagnose tuberculosis.

PMID- 16885595
TI  - Low carbohydrate diets for weight loss: historical & environmental perspective.
AB  - Obesity in the past was only seen in great numbers in Western countries but is
      now gaining prevalence in India with a growing Indian economy. Historically a
      favourable phenotype, obesity has been associated with multiple diseases
      affecting almost all organ systems. In addition, the cost of obesity to a health
      care system is enormous. Weight loss improves many of the outcomes and yet is a
      difficult process for most patients with even the medical community baffled about
      methods for weight loss. Our group and others have looked at weight loss in obese
      individuals using a low carbohydrate diet and have shown some success at six
      months and one year. Many studies have also shown a decrease in insulin
      resistance and improvement in lipid profiles when obese individuals are placed on
      a low carbohydrate diet. The reason for weight loss on this diet was initially
      thought to be diuresis from increased ketone production but it may be due to
      decreased insulin concentrations causing a decrease in appetite. In addition,
      lowering carbohydrates limits food choice and in the process decreases overall
      calorie consumption. In the United States, an increase in calories, predominantly
      from carbohydrates, appears to parallel the obesity epidemic. However, it is not
      known if guidelines or policies lowering carbohydrates in normal or slightly
      overweight individuals may help prevent obesity and its complications. Equally
      less known, is the applicability of a low carbohydrate diet to populations like
      India where many main dishes are carbohydrate-based.

PMID- 16885596
TI  - Mycobacterium leprae interactions with the host cell: recent advances.
AB  - The significance of Hansen disease, or leprosy, is underscored by fact that
      detection of this disease has remained stable over the past 10 yr, even though
      disease prevalence is reduced. Due to the long incubation time of the organism,
      health experts predict that leprosy will be with us for decades to come. Despite
      the fact that Mycobacterium leprae, the causative agent of leprosy, cannot be
      cultured in the laboratory, researchers are using innovative and imaginative
      techniques to discern the interactions of M. leprae with host cells both in vitro
      and in vivo to identify the host and bacterial factors integral to establishment
      of disease. The studies described in this review present a new and evolving
      picture of the many interactions between M. leprae and the host. Specific
      attention will be given to interactions of M. leprae bacilli with host Schwann
      cells, macrophages, dendritic cells and endothelial cells. The findings described
      also have implications for the prevention and treatment of leprosy.

PMID- 16885597
TI  - Molecular characterization of hepatitis A virus from a large outbreak from
      Kerala, India.
AB  - BACKGROUND & OBJECTIVES: Hepatitis A is highly prevalent in India and mainly
      presents as a sporadic disease. This study investigated an outbreak of viral
      hepatitis at Medical College Hospital area, Kottayam, Kerala state, India during
      January 2005. METHODS: Blood (133), faecal (1), sewage (4), and water samples
      (13) were collected. Sera were tested for IgG- and IgM-anti-HAV and IgM
      antibodies against hepatitis E (IgM-anti-HEV). Sewage, faeces and water samples
      were tested for HAV RNA in nested RT-PCR and HAV RNA positive samples were
      further processed for RNA quantitation using Real Time PCR. RESULTS: Of the 1180
      total cases, 540 were reported from Medical college area. Two deaths were
      reported among doctors. Patients from the community gave a previous history of
      visit to medical college hospital area. The sewage treatment plant at the campus
      was non-functional since 1990 and the untreated sewage was constantly overflowing
      and getting mixed with a canal. At the time of the study, all the water sources
      were superchlorinated. HAV RNA was present in the faeces of hepatitis A patient
      (1.36 x 10(7) copies/ml), sewage tank (2.57 x 10(3) copies/ml and the canal (<100
      copies/ml). None of the 13 water samples concentrated 10,000-fold and the soil
      sample showed presence of HAV RNA. Phylogenetic analysis based on 5'-non-coding
      and P2 regions showed HAV-genotype IIIA in all samples. INTERPRETATION &
      CONCLUSION: The aetiological agent of the present outbreak was found to be HAV.
      Epidemic hepatitis A (genotype-IIIA) is emerging in Indian adults, emphasizing
      the need for definite policy for control.

PMID- 16885598
TI  - Chlamydia trachomatis infection & female infertility.
AB  - BACKGROUND & OBJECTIVES: Chlamydia trachomatis is a well recognized sexually
      transmitted pathogen. Besides its potential to produce genital tract infection,
      C. trachomatis is increasingly being associated with long-term complications like
      infertility. The present study was undertaken to assess the role of C.
      trachomatis in female infertility as such data are lacking. METHODS: Women of
      primary and secondary infertility (n=110) and 30 healthy term pregnant women as
      control group were enrolled in the study. Detailed clinical history of each
      patient was recorded. Hysterosalpingography was performed in all patients.
      Endocervical swabs were collected for culture on cycloheximide treated McCoy cell
      line and for antigen detection by ELISA. RESULTS: C. trachomatis was detected in
      31 (28.1%) of the 110 infertile women while one (3.3%) in control group was
      positive for C. trachomatis (P<0.01). Cell culture alone identified 25 (22.72%)
      patients suffering from chlamydial infection while C. trachomatis antigen was
      detected by ELISA in 18 (16.37%) patients. The one control case was positive for
      Chlamydia antigen by ELISA and not by cell culture. Chlamydial positivity was
      seen in 20 of the 74 (27%) women with primary infertility and in 11 of the 36
      (30.6%) with secondary infertility. Of the 58 asymptomatic women, 21(36.2%) had
      chlamydia infection while among the 52 symptomatic cases 10 (19.2%) were
      infected; 38 per cent women with chlamydial infection also had tubal occlusion.
      INTERPRETATION & CONCLUSION: A significantly high rate of C. trachomatis
      infection was found in infertile women and more so in asymptomatic females and in
      secondary infertility cases. Lack of symptoms make clinical diagnosis of
      chlamydial infection difficult. Screening of infertile women for C. trachomatis
      is therefore recommended so far early therapeutic interventions.

PMID- 16885599
TI  - A novel method of staining acid-fast bacilli in sputum containers.
AB  - BACKGROUND & OBJECTIVES: Making centrifuged deposit smears from sputum to detect
      acid-fast bacilli (AFB) is considered hazardous. We carried out this study to
      stain the centrifuged deposits with carbol-fuchsin in sputum containers and to
      decolourize and counterstain their smears made on glass slides. METHODS: The
      centrifuged deposits of 180 sputum samples from pulmonary tuberculosis patients
      were used for making smears (initial deposit smears) and staining by Ziehl
      Neelsen (ZN) method for the detection of AFB. Each of the sputum deposit was then
      treated with one ml of 1 per cent carbol-fuchsin and a smear made between 2 to 3
      h was then decolourized and counterstained by the same procedures followed in ZN
      method (2 h stained deposit smear). The coded initial deposit smears and the
      corresponding 2 h stained deposit smears were read by the same readers and the
      results compared. RESULTS: One hundred and fifty (70 positive and 80 negative) 2
      h stained deposit smears were compared with initial deposit smears and the
      difference was not statistically significant. INTERPRETATION & CONCLUSION:
      Centrifuged deposits of sputum in sputum containers can be stained by carbol
      fuchsin within 2-3 h and their smears made subsequently on glass slides can then
      be decolourized and counterstained by the procedures followed in ZN method for
      detection of AFB by light microscopy.

PMID- 16885601
TI  - Disease mapping using mixture distribution.
AB  - BACKGROUND & OBJECTIVES: Data on infectious diseases like tuberculosis (TB) have
      been analyzed in the past without giving adequate attention to spatial
      variations. Earlier studies also attempted to display disease status of sub
      regions, usually census tracts, by categorizing them into quartiles, that helps
      the authorities to identify high- or low-risk areas. This approach is based
      mainly on binomial and Poisson models for disease data, and the recent attempts
      focus on using mixture models of Poisson distribution. We carried out this study
      to find wards of Madurai Corporation having high risks for TB disease, to develop
      a model of mixture of Poisson distributions for the number of cases and to
      classify each ward to one of many risk groups for TB disease, and to represent
      spatial distribution of TB incidence in Madurai city. METHODS: produced the
      observed counts of TB patients in 72 wards of Madurai Corporation. The number of
      risk groups and the Poisson parameters of each group were found by maximum
      likelihood approach using the computer package C.A.MAN (Computer Assisted Mixture
      ANalysis). Bayesian methods were used to associate each ward to a particular risk
      group. The results were geographically presented in maps by using ArcView mapping
      software. RESULTS: Using binomial model, 26 wards were categorized as high risk
      wards, and with mixture model approach 15 wards showed standardized morbility
      ratio (SMR) >1. The wards along river Vaigai and densely populated wards had high
      risk. INTERPRETATION & CONCLUSION: Our findings demonstrate the usefulness of the
      mixture models for disease data with geographical variations.

PMID- 16885600
TI  - Impact of oral vitamin E supplementation on oxidative stress & lipid peroxidation
      in patients with polymorphous light eruption.
AB  - BACKGROUND & OBJECTIVES: Polymorphous light eruption (PMLE) is a photo-induced
      disease which clinically manifests in the form of pruritic eruptions on sun/light
      exposed parts. Little is known about lipid peroxidation and free radical
      scavengers in patients during PMLE. The present study was therefore undertaken to
      evaluate oxidative stress and levels of antioxidant enzymes in patients of PMLE.
      METHODS: The PMLE was diagnosed clinically by a consultant dermatologist and
      validated independently by another and through histopathologic findings. Blood
      samples were collected on day 1 and patients were given oral vitamin E
      supplementation (400 mg OD) along with topical sunscreen and advice for photo
      protection. Samples were collected again after one week. The blood samples were
      evaluated for lipid peroxidation, oxygen free radical (OFR) scavenging enzymes,
      glutathione (GSH) and related enzymes such as glutathione reductase (GR),
      glutathione peroxidase (GPx), gamma glutamyl transpeptidase (GGT) and glutathione
      S-transferase (GST) in erythrocytes and compared with healthy controls. RESULTS:
      The serum malondialdehyde (MDA) level was higher and GSH level was lower in PMLE
      cases as compared to controls. There was a significant decrease in superoxide
      dismutase (SOD) activity while activities of catalase (CAT) and glutathione
      related enzymes were increased in PMLE cases. Administration of oral vitamin E
      for one week, along with photoprotection resulted in a significant decrease in
      MDA levels and activities of all others enzymes except SOD. The GSH was
      replenished and returned to normal. INTERPRETATION & CONCLUSION: Oxidative stress
      and differential modulation of antioxidant enzymes in PMLE might play a
      pathogenic role in humans, which supports the incorporation of antioxidant drugs
      in the treatment protocol of the disease.

PMID- 16885602
TI  - Gastroprotective effect of Cissus quadrangularis extract in rats with
      experimentally induced ulcer.
AB  - BACKGROUND & OBJECTIVES: Most of the non-steroidal anti-inflammatory drugs
      (NSAIDs) including aspirin cause gastric ulcer. In order to study the
      gastroprotective effect of Cissus quadrangularis extract (CQE), this study was
      undertaken on aspirin-induced ulcerogenesis in pyloric ligated (ASP-PL) model in
      rats. METHODS: To assess the possible antiulcer effect of CQE, lesion index,
      gastric secretions glycoprotein levels, non-protein sulphydryls (NPSH) and
      adherent mucus content were determined in ASP-PL induced gastric mucosal injury
      in rats. RESULTS: Pretreatment with CQE significantly prevented the gastric
      mucosal lesion development and decreased the gastric toxicity produced by
      ulcerogen. In addition, ulcerated rats showed depletion of gastric wall mucus,
      glycoproteins and NPSH levels whereas treatment with CQE reverted this decline in
      ASP-PL induced rats. Histological studies confirmed the results. INTERPRETATION &
      CONCLUSION: The present finding suggests that CQE promotes ulcer protection by
      the decrease in ulcer index, gastric secretions and increase in the glycoprotein
      level, gastric mucin content and NPSH concentration. CQE may protect the gastric
      mucosa against ulceration by its antisecretory and cytoprotective property.

PMID- 16885603
TI  - Association of conversion & cure with initial smear grading among new smear
      positive pulmonary tuberculosis patients treated with Category I regimen.
AB  - BACKGROUND & OBJECTIVES: Early diagnosis of tuberculosis (TB) is important for
      initiating treatment to gain cure. The present investigation was undertaken to
      study the association of conversion and cure with initial smear grading among
      pulmonary tuberculosis (TB) patients registered in a directly observed treatment 
      short course (DOTS) programme in Tiruvallur district, south India. METHODS: All
      new smear positive cases registered from May, 1999 to December, 2002 were
      analysed for conversion and cure related to initial smear grading. RESULTS: Of
      the 1463 patients, 1206(82.4%) were converted at the end of the intensive phase
      and 1109 (75.8%) were declared 'cured' after the completion of treatment. The
      cure rate decreased as the initial smear grading increased and the decrease in
      trend was statistically significant (P=0.01). Similarly, a significant decrease
      in conversion rate was also observed with increase in initial smear grading
      (P<0.001). In multivariate analysis, lower cure rate was significantly associated
      with patient's age (AOR=1.5, 95% CI=1.1-2.1), alcoholism (AOR=1.7, 95% CI 1.2-
      2.4) and conversion at the end of intensive phase (AOR=3.5, 95% CI= 2.6-4.8).
      INTERPRETATION & CONCLUSION: Cure and conversion rates were linearly associated
      with initial smear grading. High default and death rates were responsible for low
      cure and conversion. The proportion of patients who required extension of
      treatment and those who had an unfavourable treatment outcome were significantly
      higher among patients with a 3+ initial smear grading. This reiterates the need
      to pay more attention in motivating these patients to return to regular treatment
      and sustained commitment in the control of tuberculosis. There is a need to
      extend the treatment for one more month in the intensive phase of treatment.

PMID- 16885604
TI  - Interleukin-1 receptor antagonist gene polymorphism in patients with rheumatoid
      arthritis in India.
AB  - BACKGROUND & OBJECTIVES: Interleukin-1 receptor antagonist (IL-1Ra) is a
      naturally occurring anti-inflammatory molecule that blocks action of IL-1.
      Polymorphism in IL-1Ra gene intron 2 results in differences in production of IL
      1Ra. These polymorphisms are reportedly associated with autoimmune disease
      susceptibility in different studies. However, such data are lacking from India.
      We undertook this study to examine the IL-1Ra polymorphism as a susceptibility
      marker in patients with rheumatoid arthritis (RA). METHODS: DNA samples from 107
      patients with RA and 111 healthy controls were used to study genotypes of the IL
      1RA gene by PCR. Allelic frequencies and carriage rates were calculated and
      compared in both the groups. RESULTS: Among the 107 patients with RA, 93 were
      females and 75 per cent were seropositive for rheumatoid factor. The frequencies
      of IL-1RA alleles in controls were as follows: Allele 1 (IL- 1RN*1) was 83.33 per
      cent, IL-1RA allele 2 (IL-1RN*2) was 16.21 per cent and allele 3 (0.46%). In RA
      patients the allele frequencies were 84.11 per cent for IL-1RN*1, 14.95 per cent
      for IL- 1RN*2, 0.47 per cent each for IL-1RN*3 and IL-1RN*4. There was no
      difference in frequency of different alleles between the two groups. However,
      homozygosity for allele 2 was more frequent in controls (9.91%) as compared to
      patients (4.67%). INTERPRETATION & CONCLUSION: Our findings indicated that IL-1RA
      polymorphism was not a susceptibility marker in RA nor did it show any
      association with seropositivity, Sjogren's syndrome or subcutaneous nodules.
      Further studies with large sample need to be done to confirm these findings.

PMID- 16885605
TI  - Toxigenicity testing of clinical isolates of non-typhoidal salmonellae in Vero
      cell culture & Caenorhabditis elegans model.
AB  - The non-typhoidal salmonellae (NTS) are recognized agents of gastroenteritis
      worldwide. Some of the NTS do not produces cytotoxic changes in tissue culture
      and not much is known about the endotoxicity of the clinical isolates of NTS
      (mostly Salmonella enterica serotype Typhimurium and Salmonella enterica serotype
      Enteritidis). We examined the exotoxic (cytotoxin) and endotoxic activity of
      clinical isolates of NTS in two assay models namely Vero cell culture and the
      nematode, Caenorhabditis elegans. Bacteria-free culture supernatants of 40
      isolates NTS were tested in 96 well microtitre plate containing confluent
      monolayers of Vero cells. For the effects on C. elegans, the worms were exposed
      to bacteria free culture supernatants in 24 well microtitre plate for 24 h and
      then transferred to OP50 Escherichia coli lawn culture. The endotoxic activity of
      the live bacterium was studied by feeding the worms in the lawn culture of NTS
      separately. No cytopathic effect was observed with NTS tested in Vero cell
      culture assay. Likewise, the worms exposed to the bacteria-free culture
      supernatants were found active up to 7 days. In the co-culture killing assay,
      worms were found dead with characteristic stiff and straight appearance by 16(th)
      day. The worms were alive up to 21 days in OP50 E. coli. Bacteria-free culture
      supernatants did not have any deleterious effect on worms or in Vero cell
      culture, suggesting that there is no soluble toxic factor (diffusible toxin) in
      the culture supernatants. However, live NTS were found to be lethal to the worms;
      indicating that direct interaction between viable NTS and C. elegans is necessary
      for killing.

PMID- 16885607
TI  - Keeping the promise in stopping HIV/AIDS: can India succeed?

PMID- 16885606
TI  - Iodine deficiency disorders among the pregnant women in a rural hospital of West
      Bengal.
AB  - BACKGROUND & OBJECTIVES: Iodine deficiency disorder (IDD) is a major nutritional
      problem in India. The pregnant women and their neonates have been important
      target groups for study of the prevalence of IDD in a community. No such study
      was available to assess the prevalence of IDD among the pregnant women and
      neonates in the state of West Bengal. The present study was undertaken to assess
      the status of IDD in the pregnant women and its effect on the neonatal thyroid
      function in Burdwan district of West Bengal. METHODS: The present study was a
      hospital-based, cross-sectional, non-interventional study among 267 full term
      pregnant mothers, and the neonates born to them. One hundred non pregnant healthy
      women were selected as controls. The overall iodine status of the pregnant and
      non pregnant women was estimated by measuring the urinary iodine excretion (UIE)
      and the serum thyroid stimulating hormone (TSH) levels. The neonatal thyroid
      function was estimated by measuring the TSH levels in their cord blood. RESULTS:
      A total of 78.4 per cent pregnant women showed UIE > 10 mug/dl with 7 per cent
      having a UIE < 5 mug/dl. The median UIE and the serum TSH values in the pregnant
      women were found to be 14.4 mug/dl and 4.1 mIU/l, respectively. No statistically
      significant difference was found when compared with the control values. Only 2.9
      per cent of the neonates showed a cord blood TSH value > 5 mIU/l which is just
      below the recommended criteria for mild endemicity for IDD in the study
      population. INTERPRETATION & CONCLUSION: Pregnant women of the study area were
      iodine repleted. The neonatal thyroid function was also within normal range. The
      findings of the present study indicates that the iodine supplementation of the
      salt should be maintained in the area with periodical surveillance.

PMID- 16885608
TI  - Seroprevalence of rubella in pregnant women in Delhi, India.

PMID- 16885609
TI  - An algorithm for automatic determination of the respiratory phases in four
      dimensional computed tomography.
AB  - Recently, several techniques have been developed to improve the quality of
      computed tomography (CT) images of the thoracic and abdominal region that are
      degraded by the interference of the scanning process and respiration. Several
      devices for respiratory-correlated CT are available for clinical usage. They are
      based on the synchronization of the acquired CT image data with the respiratory
      motion using a signal from an external respiratory monitoring system. In this
      work, some practical aspects of clinical implementation of the multi-slice 4D CT
      scanner Somatom Sensation Open (Siemens Medical Solutions, Erlangen, Germany)
      equipped with a respiratory gating system (RGS) AZ-733V (Anzai Medical, Tokyo,
      Japan) are discussed. A new algorithm developed for automatic respiratory phase
      determination needed for the reconstruction of the 4D CT images is presented.

PMID- 16885610
TI  - Implementation of biologically conformal radiation therapy (BCRT) in an
      algorithmic segmentation-based inverse planning approach.
AB  - The development of new biological imaging technologies offers the opportunity to
      further individualize radiotherapy. Biologically conformal radiation therapy
      (BCRT) implies the use of the spatial distribution of one or more radiobiological
      parameters to guide the IMRT dose prescription. Our aim was to implement BCRT in
      an algorithmic segmentation-based planning approach. A biology-based segmentation
      tool was developed to generate initial beam segments that reflect the biological
      signal intensity pattern. The weights and shapes of the initial segments are
      optimized by means of an objective function that minimizes the root mean square
      deviation between the actual and intended dose values within the PTV. As proof of
      principle, [(18)F]FDG-PET-guided BCRT plans for two different levels of dose
      escalation were created for an oropharyngeal cancer patient. Both plans proved to
      be dosimetrically feasible without violating the planning constraints for the
      expanded spinal cord and the contralateral parotid gland as organs at risk. The
      obtained biological conformity was better for the first (2.5 Gy per fraction)
      than for the second (3 Gy per fraction) dose escalation level.

PMID- 16885611
TI  - A BPF-type algorithm for CT with a curved PI detector.
AB  - Helical cone-beam CT is used widely nowadays because of its rapid scan speed and
      efficient utilization of x-ray dose. Recently, an exact reconstruction algorithm
      for helical cone-beam CT was proposed (Zou and Pan 2004a Phys. Med. Biol. 49 941
      59). The algorithm is referred to as a backprojection-filtering (BPF) algorithm.
      This BPF algorithm for a helical cone-beam CT with a flat-panel detector (FPD
      HCBCT) requires minimum data within the Tam-Danielsson window and can naturally
      address the problem of ROI reconstruction from data truncated in both
      longitudinal and transversal directions. In practical CT systems, detectors are
      expensive and always take a very important position in the total cost. Hence, we
      work on an exact reconstruction algorithm for a CT system with a detector of the
      smallest size, i.e., a curved PI detector fitting the Tam-Danielsson window. The
      reconstruction algorithm is derived following the framework of the BPF algorithm.
      Numerical simulations are done to validate our algorithm in this study.

PMID- 16885612
TI  - Spatial localization in nuclear magnetic resonance spectroscopy.
AB  - The ability to select a discrete region within the body for signal acquisition is
      a fundamental requirement of in vivo NMR spectroscopy. Ideally, it should be
      possible to tailor the selected volume to coincide exactly with the lesion or
      tissue of interest, without loss of signal from within this volume or
      contamination with extraneous signals. Many techniques have been developed over
      the past 25 years employing a combination of RF coil properties, static magnetic
      field gradients and pulse sequence design in an attempt to meet these goals. This
      review presents a comprehensive survey of these techniques, their various
      advantages and disadvantages, and implications for clinical applications.
      Particular emphasis is placed on the reliability of the techniques in terms of
      signal loss, contamination and the effect of nuclear relaxation and J-coupling.
      The survey includes techniques based on RF coil and pulse design alone, those
      using static magnetic field gradients, and magnetic resonance spectroscopic
      imaging. Although there is an emphasis on techniques currently in widespread use
      (PRESS, STEAM, ISIS and MRSI), the review also includes earlier techniques, in
      order to provide historical context, and techniques that are promising for future
      use in clinical and biomedical applications.

PMID- 16885613
TI  - In vivo study of glucose-induced changes in skin properties assessed with optical
      coherence tomography.
AB  - Recently, our in vivo studies demonstrated a strong correlation between blood
      glucose concentration and the slope of the optical coherence tomography (OCT)
      signal when the probing beam was scanned over a straight line. To improve the
      sensitivity of OCT for blood glucose monitoring, two-dimensional (2D) lateral
      scanning of the OCT probing beam was proposed. Depth-dependent changes in pig
      skin properties with variation of blood glucose concentration were revealed due
      to significant suppression of speckle noise and motion artefacts in 2D scanning
      mode. The correlation coefficient of the OCT signal slope with blood glucose
      concentration varied periodically in the range from -0.9 to +0.9 depending on
      depth. The period of variation of the correlation coefficient was 100-150 microm
      that corresponded to the distance between neighbour collagen bundles. We also
      observed a decrease of skin thickness by 10 +/- 7.5 microm with an increase of
      blood glucose concentration by 277 +/- 56 mg dl(-1). Mechanisms of glucose
      induced changes in skin properties owing to tissue layer shift caused by
      dehydration associated with the glucose osmotic effect were considered.

PMID- 16885615
TI  - On probabilistically defined margins in radiation therapy.
AB  - Margins about a target volume subject to external beam radiation therapy are
      designed to assure that the target volume of tissue to be sterilized by treatment
      is adequately covered by a lethal dose. Thus, margins are meant to guarantee that
      all potential variation in tumour position relative to beams allows the tumour to
      stay within the margin. Variation in tumour position can be broken into two types
      of dislocations, reducible and irreducible. Reducible variations in tumour
      position are those that can be accommodated with the use of modern image-guided
      techniques that derive parameters for compensating motions of patient bodies
      and/or motions of beams relative to patient bodies. Irreducible variations in
      tumour position are those random dislocations of a target that are related to
      errors intrinsic in the design and performance limitations of the software and
      hardware, as well as limitations of human perception and decision making. Thus,
      margins in the era of image-guided treatments will need to accommodate only
      random errors residual in patient setup accuracy (after image-guided setup
      corrections) and in the accuracy of systems designed to track moving and
      deforming tissues of the targeted regions of the patient's body. Therefore,
      construction of these margins will have to be based on purely statistical data.
      The characteristics of these data have to be determined through the central limit
      theorem and Gaussian properties of limiting error distributions. In this paper,
      we show how statistically determined margins are to be designed in the general
      case of correlated distributions of position errors in three-dimensional space.
      In particular, we show how the minimal margins for a given level of statistical
      confidence are found. Then, how they are to be used to determine geometrically
      minimal PTV that provides coverage of GTV at the assumed level of statistical
      confidence. Our results generalize earlier recommendations for statistical,
      central limit theorem-based recommendations for margin construction that were
      derived for uncorrelated distributions of errors (van Herk, Remeijer, Rasch and
      Lebesque 2000 Int. J. Radiat. Oncol. Biol. Phys. 47 1121-35; Stroom, De Boer,
      Huizenga and Visser 1999 Int. J. Radiat. Oncol. Biol. Phys. 43 905-19).

PMID- 16885614
TI  - Receiver operating characteristic analysis for the detection of simulated
      microcalcifications on mammograms using hardcopy images.
AB  - The aim of this study was to compare mammography systems based on three different
      detectors--a conventional screen-film (SF) combination, an a-Si/CsI flat-panel
      (FP)-based detector, and a charge-coupled device (CCD)-based x-ray phosphor-based
      detector--for their performance in detecting simulated microcalcifications (MCs).
      112-150 microm calcium carbonate grains were used to simulate MCs and were
      overlapped with a slab phantom of simulated 50% adipose/50% glandular breast
      tissue-equivalent material referred to as the uniform background. For the tissue
      structure background, 200-250 microm calcium carbonate grains were used and
      overlapped with an anthropomorphic breast phantom. All MC phantom images were
      acquired with and without magnification (1.8 X). The hardcopy images were
      reviewed by five mammographers. A five-point confidence level rating was used to
      score each detection task. Receiver operating characteristic (ROC) analysis was
      performed, and the areas under the ROC curves (A(z)s) were used to compare the
      performances of the three mammography systems under various conditions. The
      results showed that, with a uniform background and contact images, the FP-based
      system performed significantly better than the SF and the CCD-based systems. For
      magnified images with a uniform background, the SF and the FP-based systems
      performed equally well and significantly better than the CCD-based system. With
      tissue structure background and contact images, the SF system performed
      significantly better than the FP and the CCD-based systems. With magnified images
      and a tissue structure background, the SF and the CCD-based systems performed
      equally well and significantly better than the FP-based system. In the detection
      of MCs in the fibroglandular and the heterogeneously dense regions, no
      significant differences were found except that the SF system performed
      significantly better than the CCD-based system in the fibroglandular regions for
      the contact images.

PMID- 16885616
TI  - A modified simulated annealing algorithm for parameter determination for a hybrid
      virtual model.
AB  - In this work we present an algorithm based on the simulated annealing (SA) method
      for electron beam spectrum reconstruction from central axis PDD data. We use a
      simulated beam in order to assess the accuracy of the method, and compare it with
      others usually employed. We found that our modified SA algorithm produced
      excellent reconstructed PDDs and beam profiles and improved reconstructed
      spectra. We also tested our method for the simultaneous determination of an
      electron energy spectrum and the position of a trimmer from central axis PDD
      data, and found this to be sufficient for the determination of the physical
      parameters of this hybrid model.

PMID- 16885617
TI  - A combination-weighted Feldkamp-based reconstruction algorithm for cone-beam CT.
AB  - The combination-weighted Feldkamp algorithm (CW-FDK) was developed and tested in
      a phantom in order to reduce cone-beam artefacts and enhance cranio-caudal
      reconstruction coverage in an attempt to improve image quality when utilizing
      cone-beam computed tomography (CBCT). Using a 256-slice cone-beam CT (256CBCT),
      image quality (CT-number uniformity and geometrical accuracy) was quantitatively
      evaluated in phantom and clinical studies, and the results were compared to those
      obtained with the original Feldkamp algorithm. A clinical study was done in lung
      cancer patients under breath holding and free breathing. Image quality for the
      original Feldkamp algorithm is degraded at the edge of the scan region due to the
      missing volume, commensurate with the cranio-caudal distance between the
      reconstruction and central planes. The CW-FDK extended the reconstruction
      coverage to equal the scan coverage and improved reconstruction accuracy,
      unaffected by the cranio-caudal distance. The extended reconstruction coverage
      with good image quality provided by the CW-FDK will be clinically investigated
      for improving diagnostic and radiotherapy applications. In addition, this
      algorithm can also be adapted for use in relatively wide cone-angle CBCT such as
      with a flat-panel detector CBCT.

PMID- 16885618
TI  - Comparison of conventional, model-based quantitative planar, and quantitative
      SPECT image processing methods for organ activity estimation using In-111 agents.
AB  - Accurate quantification of organ radionuclide uptake is important for patient
      specific dosimetry. The quantitative accuracy from conventional conjugate view
      methods is limited by overlap of projections from different organs and background
      activity, and attenuation and scatter. In this work, we propose and validate a
      quantitative planar (QPlanar) processing method based on maximum likelihood (ML)
      estimation of organ activities using 3D organ VOIs and a projector that models
      the image degrading effects. Both a physical phantom experiment and Monte Carlo
      simulation (MCS) studies were used to evaluate the new method. In these studies,
      the accuracies and precisions of organ activity estimates for the QPlanar method
      were compared with those from conventional planar (CPlanar) processing methods
      with various corrections for scatter, attenuation and organ overlap, and a
      quantitative SPECT (QSPECT) processing method. Experimental planar and SPECT
      projections and registered CT data from an RSD Torso phantom were obtained using
      a GE Millenium VH/Hawkeye system. The MCS data were obtained from the 3D NCAT
      phantom with organ activity distributions that modelled the uptake of (111)In
      ibritumomab tiuxetan. The simulations were performed using parameters appropriate
      for the same system used in the RSD torso phantom experiment. The organ activity
      estimates obtained from the CPlanar, QPlanar and QSPECT methods from both
      experiments were compared. From the results of the MCS experiment, even with
      ideal organ overlap correction and background subtraction, CPlanar methods
      provided limited quantitative accuracy. The QPlanar method with accurate
      modelling of the physical factors increased the quantitative accuracy at the cost
      of requiring estimates of the organ VOIs in 3D. The accuracy of QPlanar
      approached that of QSPECT, but required much less acquisition and computation
      time. Similar results were obtained from the physical phantom experiment. We
      conclude that the QPlanar method, based on 3D organ VOIs and accurate models of
      the projection process, provided a substantial increase in accuracy of organ
      activity estimates from planar images compared to CPlanar processing and had
      accuracy approaching that of QSPECT.

PMID- 16885619
TI  - Fluorescence molecular tomography in the presence of background fluorescence.
AB  - Fluorescence molecular tomography is an emerging imaging technique that resolves
      the bio-distribution of engineered fluorescent probes developed for in vivo
      reporting of specific cellular and sub-cellular targets. The method can detect
      fluorochromes in picomole amounts or less, imaged through entire animals, but the
      detection sensitivity and imaging performance drop in the presence of background,
      non-specific fluorescence. In this study, we carried out a theoretical and an
      experimental investigation on the effect of background fluorescence on the
      measured signal and on the tomographic reconstruction. We further examined the
      performance of three subtraction methods based on physical models of photon
      propagation, using experimental data on phantoms and small animals. We show that
      the data pre-processing with subtraction schemes can improve image quality and
      quantification when non-specific background florescence is present.

PMID- 16885620
TI  - Evaluation of transmission methodology and attenuation correction for the
      microPET Focus 220 animal scanner.
AB  - An accurate, low noise estimate of photon attenuation in the subject is required
      for quantitative microPET studies of molecular tracer distributions in vivo. In
      this work, several transmission-based measurement techniques were compared,
      including coincidence mode with and without rod windowing, singles mode with two
      different energy sources ((68)Ge and (57)Co), and postinjection transmission
      scanning. In addition, the effectiveness of transmission segmentation and the
      propagation of transmission bias and noise into the emission images were
      examined. The (57)Co singles measurements provided the most accurate attenuation
      coefficients and superior signal-to-noise ratio, while (68)Ge singles
      measurements were degraded due to scattering from the object. Scatter correction
      of (68)Ge transmission data improved the accuracy for a 10 cm phantom but over
      corrected for a mouse phantom. (57)Co scanning also resulted in low bias and
      noise in postinjection transmission scans for emission activities up to 20 MBq.
      Segmentation worked most reliably for transmission data acquired with (57)Co but
      the minor improvement in accuracy of attenuation coefficients and signal-to-noise
      may not justify its use, particularly for small subjects. We conclude that (57)Co
      singles transmission scanning is the most suitable method for measured
      attenuation correction on the microPET Focus 220 animal scanner.

PMID- 16885621
TI  - Penalized maximum-likelihood image reconstruction for lesion detection.
AB  - Detecting cancerous lesions is one major application in emission tomography. In
      this paper, we study penalized maximum-likelihood image reconstruction for this
      important clinical task. Compared to analytical reconstruction methods,
      statistical approaches can improve the image quality by accurately modelling the
      photon detection process and measurement noise in imaging systems. To explore the
      full potential of penalized maximum-likelihood image reconstruction for lesion
      detection, we derived simplified theoretical expressions that allow fast
      evaluation of the detectability of a random lesion. The theoretical results are
      used to design the regularization parameters to improve lesion detectability. We
      conducted computer-based Monte Carlo simulations to compare the proposed penalty
      function, conventional penalty function, and a penalty function for isotropic
      point spread function. The lesion detectability is measured by a channelized
      Hotelling observer. The results show that the proposed penalty function
      outperforms the other penalty functions for lesion detection. The relative
      improvement is dependent on the size of the lesion. However, we found that the
      penalty function optimized for a 5 mm lesion still outperforms the other two
      penalty functions for detecting a 14 mm lesion. Therefore, it is feasible to use
      the penalty function designed for small lesions in image reconstruction, because
      detection of large lesions is relatively easy.

PMID- 16885622
TI  - The influence of acoustic transmit parameters on the destruction of contrast
      microbubbles in vitro.
AB  - In this study, the destruction of the contrast agent Sonazoid (GE Healthcare,
      Oslo, Norway) was measured in vitro as a function of centre frequency (2-3 MHz),
      acoustic amplitude (0.66-1.6 MPa), pulse length (2-16 cycles) and PRF (0.5-8.0
      kHz). Up to 82% of microbubbles were destroyed after exposure to a single 1.6 MPa
      acoustic pulse (16 cycles, 2.5 MHz and PRF of 1.0 kHz), while at a low amplitude
      of 0.66 MPa, fractional destruction increased gradually from 0 to 40% after
      exposure to 9 (identical) pulses. Fractional destruction increased from
      approximately 8 to 66% as pulse length was changed from 2 to 16 cycles following
      exposure to a single 2.5 MHz, 1.3 MPa pulse. As the PRF was increased from 0.5 to
      8.0 kHz, shorter exposure time intervals (from 4.8 to 1.2 ms) were needed to
      achieve the same fractional destruction of 80%. Conversely, as the transmit
      frequency was increased from 2 to 3 MHz the fractional destruction decreased (by
      more than half within the first 3 pulses). The influence of changes in acoustic
      pressure and duty cycle on the destruction of Sonazoid microbubbles was highly
      statistically significant (p < or = 0.01) with a threshold around 0.67 MPa for a
      duty cycle of 0.0064. In conclusion, the fractional destruction increases with
      the duty cycle and the acoustic pressure amplitude and decreases with ultrasonic
      transmit frequency. Better understanding of the influence of the ultrasound
      transmit parameters on the destruction of contrast microbubbles should help
      improve existing contrast-assisted imaging modalities and may help develop new
      techniques for better use of contrast agents.

PMID- 16885624
TI  - Halftime for repair of sublethal damage in normal bladder and rectum: an analysis
      of clinical data from cervix brachytherapy.
AB  - The halftime for repair of sub-lethal damage is an important radiobiological
      parameter in analysing radiation responses and in designing new treatments
      involving different dose rates. This work is to resolve an inconsistency existing
      in the repair halftime for the bladder and rectum, two of the most dose limiting
      critical structures for pelvic irradiation. Both long (1.5-2 h) and short (0.3-1
      h) repair halftimes have been reported previously. In this work, by reconciling
      clinical data from cervical brachytherapy of different dose rates and by
      introducing a sparing factor to consider the dose sparing occurring for critical
      structures, we have estimated that the most likely value of the repair halftime
      for bladder and rectum is short, 0.2-0.4 h if assuming alpha/beta = 2-4 Gy. The
      present analysis does not support the long repair halftimes reported previously
      for the bladder and rectum and for other normal structures.

PMID- 16885623
TI  - 3D source localization of interictal spikes in epilepsy patients with MRI
      lesions.
AB  - The present study aims to accurately localize epileptogenic regions which are
      responsible for epileptic activities in epilepsy patients by means of a new
      subspace source localization approach, i.e. first principle vectors (FINE), using
      scalp EEG recordings. Computer simulations were first performed to assess source
      localization accuracy of FINE in the clinical electrode set-up. The source
      localization results from FINE were compared with the results from a classic
      subspace source localization approach, i.e. MUSIC, and their differences were
      tested statistically using the paired t-test. Other factors influencing the
      source localization accuracy were assessed statistically by ANOVA. The interictal
      epileptiform spike data from three adult epilepsy patients with medically
      intractable partial epilepsy and well-defined symptomatic MRI lesions were then
      studied using both FINE and MUSIC. The comparison between the electrical sources
      estimated by the subspace source localization approaches and MRI lesions was made
      through the coregistration between the EEG recordings and MRI scans. The accuracy
      of estimations made by FINE and MUSIC was also evaluated and compared by R(2)
      statistic, which was used to indicate the goodness-of-fit of the estimated
      sources to the scalp EEG recordings. The three-concentric-spheres head volume
      conductor model was built for each patient with three spheres of different radii
      which takes the individual head size and skull thickness into consideration. The
      results from computer simulations indicate that the improvement of source spatial
      resolvability and localization accuracy of FINE as compared with MUSIC is
      significant when simulated sources are closely spaced, deep, or signal-to-noise
      ratio is low in a clinical electrode set-up. The interictal electrical generators
      estimated by FINE and MUSIC are in concordance with the patients' structural
      abnormality, i.e. MRI lesions, in all three patients. The higher R(2) values
      achieved by FINE than MUSIC indicate that FINE provides a more satisfactory
      fitting of the scalp potential measurements than MUSIC in all patients. The
      present results suggest that FINE provides a useful brain source imaging
      technique, from clinical EEG recordings, for identifying and localizing
      epileptogenic regions in epilepsy patients with focal partial seizures. The
      present study may lead to the establishment of a high-resolution source
      localization technique from scalp-recorded EEGs for aiding presurgical planning
      in epilepsy patients.

PMID- 16885625
TI  - Application of heavy-ion CT.
AB  - In treatment planning for hadron therapy, information about the relative stopping
      power in a patient's body is used to calculate the range of incident ions. This
      information is obtained from computed tomography (CT) images using a conversion
      table from x-ray CT numbers into stopping powers relative to the stopping power
      of water. In treatment planning at the National Institute of Radiological
      Sciences (NIRS), the conversion table has been created based on the polybinary
      tissue model. However, it has not been fully verified that the model is accurate
      enough for use in real animal tissues. In order to irradiate heavy ions more
      precisely in radiotherapy, we have to evaluate the accuracy of the polybinary
      tissue calibration in animal tissues. We have measured animal tissue samples with
      a heavy-ion CT (HICT) and an x-ray CT. The x-ray CT image was converted to an
      image of relative stopping power by using the table derived from the polybinary
      tissue calibration (polybinary-tissue-model CT (PTCT) image). On the other hand,
      with HICT, the two-dimensional distribution of relative stopping power can be
      obtained directly. A comparison between PTCT and HICT images enabled us to verify
      the accuracy of the conversion table derived from the polybinary tissue
      calibration. Consequently, it was found that the agreement between the relative
      stopping powers of PTCT and HICT is 1.6% for fat, muscle and bone.

PMID- 16885626
TI  - Comparison of dose distributions around the pulsed-dose-rate Fletcher-Williamson
      and the low-dose-rate Fletcher-Suit-Delclos ovoids: a Monte Carlo study.
AB  - We performed a Monte Carlo study to compare dose distributions for a Fletcher
      Suit-Delclos (FSD) ovoid used with (137)Cs low-dose-rate (LDR) sources with those
      for a Fletcher-Williamson (FW) ovoid used with an (192)Ir pulsed-dose-rate (PDR)
      source for intracavitary brachytherapy of cervical cancer. We recently reported
      on extensive validation of Monte Carlo MCNPX models of these ovoids using
      radiochromic film measurements. Here, we compared these models assuming identical
      loading of 10, 15 and 20 mgRaEq (72, 108 and 145 cGy cm(2) h(-1), respectively)
      in three dose mesh planes: one perpendicular to the ovoid long axis bisecting the
      ovoid, one parallel to and displaced 2 cm medially from the long axis of the
      ovoid, and a 'rectal' plane perpendicular to the long axis located 1 cm distal to
      the distal face of the ovoid cap. The FW ovoid delivered slightly higher doses
      (within 10%) over all loadings to regions away from the bladder and rectal
      shields when compared to the FSD ovoid. However, the FW ovoid delivered much
      higher doses (>50%) in regions near these shields. In the rectal plane, the FW
      ovoid delivered a slightly higher dose, but within the region directly behind the
      rectal shield, the FW ovoid delivered a dose ranging from +35% to -35% of the FSD
      dose distribution. We attribute these differences to intrinsic differences in
      source characteristics (radial dose function and anisotropy factors) and
      extrinsic factors such as the solid-angle effect between sources and shields and
      applicator design.

PMID- 16885627
TI  - TPD-based evaluation of near threshold mono-energetic proton energies for the
      (7)Li(p,n)(7)Be production of neutrons for BNCT.
AB  - An evaluation of mono-energetic proton energies ranging from 1.885 MeV to 1.920
      MeV was carried out to determine the viability of these near threshold energies
      in producing neutrons for BNCT via the (7)Li(p,n)(7)Be reaction. Neutron fields
      generated at these proton energies were assessed using the treatable protocol
      depth (TPD) and the maximum TPD (TPD(max)) as evaluation indices. The heavy
      charged particle (HCP) dose rate to tumour was likewise applied as a figure of
      merit in order to account for irradiation time and required proton current.
      Incident proton energies closer to the reaction threshold generated deeper TPDs
      compared to higher energy protons when no boron dose enhancers (BDE) were placed
      in the irradiation field. Introducing a BDE resulted in improved TPDs for high
      proton energies but their achievable TPD(max) were comparatively lower than that
      obtained for lower proton energies. In terms of the HCP dose rate to tumour,
      higher proton energies generated neutron fields that yielded higher dose rates
      both at TPD(max) and at fixed depths of comparison. This infers that higher
      currents are required to deliver the prescribed treatment dose to tumours for
      proton beams with energies closer to the (7)Li(p,n)(7)Be reaction threshold and
      more achievable proton currents of around 10 mA or less for proton energies from
      1.900 MeV and above. The dependence on incident proton energy of the TPD,
      TPD(max) and the HCP dose rate to tumour with respect to the (10)B concentration
      in tumour and healthy tissues were also clarified in this study. Increasing the
      (10)B concentration in tumour while maintaining a constant T/N ratio resulted in
      deeper TPD(max) where a greater change in TPD(max) was obtained for proton
      energies closer to the (7)Li(p,n)(7)Be reaction threshold. The HCP dose rates to
      tumour for all proton energies also went up, with the higher proton energies
      benefiting more from the increased (10)B concentration.

PMID- 16885628
TI  - Modelling lateral beam quality variations in pencil kernel based photon dose
      calculations.
AB  - Standard treatment machines for external radiotherapy are designed to yield flat
      dose distributions at a representative treatment depth. The common method to
      reach this goal is to use a flattening filter to decrease the fluence in the
      centre of the beam. A side effect of this filtering is that the average energy of
      the beam is generally lower at a distance from the central axis, a phenomenon
      commonly referred to as off-axis softening. The off-axis softening results in a
      relative change in beam quality that is almost independent of machine brand and
      model. Central axis dose calculations using pencil beam kernels show no drastic
      loss in accuracy when the off-axis beam quality variations are neglected.
      However, for dose calculated at off-axis positions the effect should be
      considered, otherwise errors of several per cent can be introduced. This work
      proposes a method to explicitly include the effect of off-axis softening in
      pencil kernel based photon dose calculations for arbitrary positions in a
      radiation field. Variations of pencil kernel values are modelled through a
      generic relation between half value layer (HVL) thickness and off-axis position
      for standard treatment machines. The pencil kernel integration for dose
      calculation is performed through sampling of energy fluence and beam quality in
      sectors of concentric circles around the calculation point. The method is fully
      based on generic data and therefore does not require any specific measurements
      for characterization of the off-axis softening effect, provided that the machine
      performance is in agreement with the assumed HVL variations. The model is
      verified versus profile measurements at different depths and through a model self
      consistency check, using the dose calculation model to estimate HVL values at off
      axis positions. A comparison between calculated and measured profiles at
      different depths showed a maximum relative error of 4% without explicit modelling
      of off-axis softening. The maximum relative error was reduced to 1% when the off
      axis softening was accounted for in the calculations.

PMID- 16885629
TI  - Selective contralateral balloon occlusion for successful opening of a
      persistently collapsed lung in congenital lobar emphysema.

PMID- 16885630
TI  - Ileocecal intussusception following appendectomy.

PMID- 16885631
TI  - What's your diagnosis: Peutz-Jeghers syndrome with jejunal and colonic
      intussusception.

PMID- 16885632
TI  - Asymmetrical tetraphocomelia with radiohumeral synostosis.

PMID- 16885633
TI  - Wunderlich syndrome following rupture of a renal angiomyolipoma.

PMID- 16885634
TI  - A child with an acanthocephalan infection.

PMID- 16885635
TI  - Attitude towards MRI safety during pregnancy.

PMID- 16885636
TI  - Pressure ulcer risk: Gazing into a crystal ball?

PMID- 16885642
TI  - Nutritional considerations in wound care.

PMID- 16885644
TI  - Mid-year update: Medicare physician fee schedule and average sales prices for
      wound care products and services.

PMID- 16885643
TI  - When is it appropriate to photograph a patient's wound?

PMID- 16885645
TI  - Experience with the use of apligraf to heal complicated surgical and nonsurgical
      wounds in a private practice setting.
AB  - Apligraf is supplied as a ready-to-use living fibroblast and keratinocyte bilayer
      in culture. This therapy has been shown to facilitate healing of venous ulcers
      and diabetic foot ulcers. Several case reports suggest that Apligraf may also be
      effective in healing acute excisional wounds and complicated surgical defects.
      Apligraf can, in appropriate settings, be used as an alternative to autografts,
      avoiding the morbidity of donor site wounds. The present case review summarizes
      outcomes in 16 patients with 18 complicated surgical and nonsurgical wounds
      treated with Apligraf, which was meshed or fenestrated as needed to obtain better
      wound coverage and to allow drainage. Of 16 patients, 15 (94%) experienced
      complete healing (16 of 18 wounds; 89%). Both surgical and nonsurgical wounds
      responded well, with healing times ranging from 21 to 550 days. Patients
      generally stated that they were satisfied with their degree of healing and with
      the opportunity to avoid the surgical procedures associated with autograft donor
      sites.

PMID- 16885646
TI  - MMP-2 assessment as an indicator of wound healing: A feasibility study.
AB  - OBJECTIVE: Evaluate the feasibility of assessment of fibroblast matrix
      metalloproteinase-2 (MMP-2) expression as an indicator of wound healing in wounds
      that change from chronically inert to actively healing. METHODS: Phase II
      feasibility study of 4 patients with nonhealing wounds (duration, > or = 3
      months; surface area, > or = 1 cm). Wounds were treated with a dressing
      impregated with oak bark extract (DerMax) and evaluated weekly; biopsies were
      performed every 2 weeks until wound healing. RESULTS: Therapy-induced wound
      healing and immunohistochemical measurements of MMP-2 expression paralleled the
      clinical characteristics of wound healing. CONCLUSION: MMP-2 expression offers a
      reliable indicator for clinical wound healing induced by DerMax treatment.

PMID- 16885647
TI  - Hand-to-hand combat: Preventing MRSA infection.
AB  - PURPOSE: To provide practitioners with a general overview of community-acquired
      methicillin-resistant Staphylococcus aureus (CA-MRSA) and hospital-acquired
      methicillin-resistant Staphylococcus aureus (HA-MRSA) and their diagnoses and
      treatment. TARGET AUDIENCE: This continuing education activity is intended for
      physicians and nurses with an interest in preventing, diagnosing, and treating
      MRSA infection. OBJECTIVES: After reading this article and taking the test, the
      participant should be able to: 1. Discuss the microbiology, demographics, and
      epidemiology of CA-MRSA and HA-MRSA. 2. Explain the diagnosis, treatment, and
      preventative care associated with MRSA infections.

PMID- 16885651
TI  - Screening for ovarian cancer.
AB  - The efficacy of ovarian cancer screening remains to be proven. Advances in
      ultrasound and tumor marker technology, combined with complex statistical
      analysis have facilitated 2 large ongoing randomized controlled trials of
      screening which are powered to determine the impact on mortality. Serum
      proteomics seems to be a promising area for biomarker discovery, but requires
      more rigorous validation before it can be used in clinical trials. Current
      screening tests, clinical trials in the general and high-risk populations,
      screening acceptability and costs are reviewed in this article.

PMID- 16885652
TI  - Guidelines for referral of the patient with an adnexal mass.
AB  - Gynecologists have to differentiate between benign and malignant adnexal masses.
      We review the evidence supporting to the specialty care of a gynecologic
      oncologist on the basis of the physical examination, imaging studies, family
      history, and CA 125 determination. We recommend adherence to the ACOG/SGO Joint
      Opinion guidelines. Specifically, referral to a gynecologic oncologist seems
      warranted for postmenopausal women with elevated CA 125, nodular or fixed pelvic
      mass, metastatic disease, ascites, or family history of breast or ovarian cancer.
      Premenopausal women should be referred if the CA 125 is elevated above 200 U/mL,
      there is an evidence of metastatic disease or ascites, or strong family history
      of breast or ovarian cancer.

PMID- 16885653
TI  - Adnexal torsion.
AB  - This review provides timely information concerning clinical, surgical, and
      pathologic findings of adnexal torsion (AT). AT mostly occurs in the child
      bearing age group, but is not uncommon in premenarchal girls or postmenopausal
      women. When AT is suspected, urgent surgical intervention is indicated, and is
      usually performed by laparoscopy. Incidence of AT is 3.5% of all benign cystic
      teratomas. Despite the "necrotic" appearance of the twisted ischemic ovary,
      detorsion is the only procedure which should be performed at surgery. Adnexectomy
      should be avoided as ovarian function is preserved in 88% to 100% of cases.
      Awareness and suspicion of the diagnosis of AT is needed in patients who present
      with lower abdominal pain.

PMID- 16885654
TI  - Adnexal masses in infancy and childhood.
AB  - The presentation of adnexal masses in childhood differs from that in adult women.
      Children may present with poorly localized symptoms or precocious puberty.
      Ovarian cysts occur throughout development; ovarian tumors are less frequent but
      occur in all age groups. Congenital malformations may present with signs or
      symptoms of an adnexal mass. Occasionally adnexal findings may suggest the
      presence of an underlying syndrome. Assessment of the patient's developmental,
      hormonal, and pubertal status is necessary to ensure an accurate diagnosis.
      Treatment options must consider risks to ovarian function and future fertility.

PMID- 16885655
TI  - Management of ovarian endometrioma.
AB  - The optimal conservative treatment for endometriotic cysts is unclear,
      particularly when treated laparoscopically. We performed a systematic analysis of
      the published literature on ovarian endometrioma especially focused on comparing
      laparoscopic cystectomy with laparoscopic drainage and coagulation of the cyst
      with regard to evaluating advantage and disadvantage of each method. We observed
      that cystectomy was superior in terms of risk of recurrent symptoms, cyst,
      reoperation, pregnancy: this was true in both prospective and retrospective
      studies previously published. Given the evidence available, excision of cyst wall
      in endometrioma is strongly recommended especially in infertile patients.

PMID- 16885657
TI  - The incidental postmenopausal adnexal mass.
AB  - The postmenopausal ovary continues to produce cysts; the prevalence in an ovarian
      cancer screening population approaches 18%. Yet 60% to 70% of unilocular cysts
      resolve spontaneously. Optimal management of an asymptomatic adnexal mass allows
      surveillance of women at low malignancy risk while triaging intermediate/high
      risk women to surgery. Women with unilocular cysts on transvaginal ultrasound
      (TVS) and a normal CA-125 are monitored with repeat TVS at 3 to 6 months. Those
      with a complex mass <5 cm and normal CA-125 should have repeat TVS and CA-125
      testing in 4 weeks. Surgery is recommended for any women with increasing
      morphologic complexity or a rising CA-125.

PMID- 16885656
TI  - Evaluation and management of adnexal masses during pregnancy.
AB  - An increase in the incidence of adnexal masses uncovered during pregnancy has
      occurred concurrently with the adoption of near universal use of prenatal
      ultrasound. The majority of these masses resolve by the second trimester.
      Persistent masses continue to be at risk for significant sequelae such as
      torsion, rupture, and obstruction of labor. These events may result in the need
      for emergent surgical intervention with increased risk of adverse outcome for
      both mother and fetus. In addition a small risk of cancer exists and extended
      delay in diagnosis should be avoided. As such, surgical excision of persistent
      adnexal masses should be entertained at approximately 16 to 20 weeks of
      gestation. In the approximately 5% of cases in which an adnexal masses proves to
      be a malignancy, appropriate staging may be safely performed. In selected cases,
      chemotherapy should at least be entertained.

PMID- 16885658
TI  - Borderline ovarian tumors: current concepts for prognostic factors and clinical
      management.
AB  - Since their original description in 1929, our knowledge of the natural history
      and molecular pathology of borderline ovarian tumors (BOTs) has advanced most
      dramatically over the last decade. It has been estimated that at the time of
      abdominal exploration for a serous ovarian neoplasm, a BOT will be discovered in
      approximately 15% of cases. These tumors commonly affect women of reproductive
      age, have an excellent overall prognosis and the majority are cured with surgery.
      Nevertheless, a subset of patients with these tumors have an adverse clinical
      outcome and the molecular features of the associated tumor subtype is currently
      being defined. These data have caused some to place this more aggressive subtype
      of BOT, called micropapillary serous with invasive extraovarian implants, into
      the pathologic continuum with frankly invasive carcinomas. This chapter will
      explore advances in our understanding of the natural history, clinical and
      pathologic features of BOTs and will conclude with a discussion of the molecular
      prognostic factors that might be targets for future therapy. A special emphasis
      will be placed on points of agreement identified during a recent workshop on BOTs
      sponsored by the National Cancer Institute (NCI).

PMID- 16885659
TI  - Ovarian remnant syndrome.
AB  - Ovarian remnant syndrome (ORS) refers to a condition occurring in women who have
      had a bilateral salpingo-oophorectomy (BSO), with or without a hysterectomy, that
      leaves behind ovarian tissue. This residual ovarian tissue then results in pelvic
      pain or a pelvic mass. Risk factors associated with incomplete removal of an
      ovary and subsequent development of ORS include a history of endometriosis,
      pelvic inflammatory disease, multiple previous surgeries, and pelvic adhesive
      disease. Patients most frequently present with chronic pelvic pain, pelvic pain
      associated with a pelvic mass, or an asymptomatic pelvic mass. Definitive
      criteria for diagnosis of ORS include a history of BSO with histologic
      documentation of ovarian tissue obtained during subsequent surgical excision. The
      recommended treatment for ORS is surgical excision by laparotomy or, more
      recently, laparoscopy. We present the presentation and management of patients
      with ORS and a review of the published literature.

PMID- 16885660
TI  - Laparoscopic management of the adnexal mass.
AB  - Ovarian neoplasms are common in women of all ages. As many as 10% of women in the
      United States will undergo surgical removal of an adnexal mass sometime in their
      lifetime. Gynecologic surgeons have pioneered laparoscopic surgery, developing
      what was originally a diagnostic tool into a safe and effective approach to
      management of adnexal masses. Accumulating scientific data support the
      laparoscopic approach to the adnexal mass as the preferred treatment.

PMID- 16885662
TI  - Cervical ripening: biochemical, molecular, and clinical considerations.
AB  - The physiologic and pathologic changes of the uterine cervix during pregnancy
      leading to cervical ripening are not well understood though are related to the
      chief pathology and a commonly performed intervention in obstetrics: Preterm
      birth and labor induction. Normal cervical ripening is thought to be controlled
      by a variety of hormonal changes occurring during pregnancy leading to softening
      and dilation. Abnormal premature ripening, usually resulting in preterm labor, is
      thought to be associated with infection and inflammatory events. Despite many
      studies of the cervix, we still rely upon relatively crude methods for clinical
      evaluation of the cervix. In the past several years, we have developed and
      evaluated a method to measure cervical collagen noninvasively using an instrument
      called Collascope. Studies in animals and humans conducted in a variety of
      settings indicate that cervical function can be successfully monitored using the
      Collascope during pregnancy. We suggest that this technique might be useful to
      better define management in cases of spontaneous preterm and induced term
      cervical ripening.

PMID- 16885663
TI  - Preinduction cervical assessment.
AB  - The rate of labor induction is increasing in the United States. Methods for
      quantifying cervical factors have been developed to identify patients who may
      benefit from cervical ripening before induction. The first cervical scoring
      systems used digital examination. More recently, cervical ultrasound and testing
      for the presence of fetal fibronectin have been suggested to evaluate cervical
      readiness for labor induction, but neither of these methods provides a
      significant improvement over digital examination. The Bishop score, the most
      widely used digital examination scoring system, still is the most cost effective
      and accurate method of evaluating the cervix before labor induction.

PMID- 16885664
TI  - Factors predicting labor induction success: a critical analysis.
AB  - Because of the risk of failed induction of labor, a variety of maternal and fetal
      factors as well as screening tests have been suggested to predict labor induction
      success. Certain characteristics of the woman (including parity, age, weight,
      height and body mass index), and of the fetus (including birth weight and
      gestational age) are associated with the success of labor induction; with parous,
      young women who are taller and lower weight having a higher rate of induction
      success. Fetuses with a lower birth weight or increased gestational age are also
      associated with increased induction success. The condition of the cervix at the
      start of induction is an important predictor, with the modified Bishop score
      being a widely used scoring system. The most important element of the Bishop
      score is dilatation. Other predictors, including transvaginal ultrasound (TVUS)
      and biochemical markers [including fetal fibronectin (fFN)] have been suggested.
      Meta-analyses of studies identified from MEDLINE, PubMed, and EMBASE and
      published from 1990 to October 2005 were performed evaluating the use of TVUS and
      fFN in predicting labor induction success in women at term with singleton
      gestations. Both TVUS and Bishop score predicted successful induction [likelihood
      ratio (LR)=1.82, 95% confidence interval (CI)=1.51-2.20 and LR=2.10, 95%CI=1.67
      2.64, respectively]. As well, fFN and Bishop score predicted successful induction
      (LR=1.49, 95%CI=1.20-1.85, and LR=2.62, 95%CI=1.88-3.64, respectively). Although
      TVUS and fFN predicted successful labor induction, neither has been shown to be
      superior to Bishop score. Further research is needed to evaluate these potential
      predictors and insulin-like growth factor binding protein-1 (IGFBP-1), another
      potential biochemical marker.

PMID- 16885665
TI  - What is a failed labor induction?
AB  - Criteria for failed labor induction have not been standardized. The increasing
      prevalence of labor induction and the lack of a definition for failed induction
      contribute to unnecessary abdominal deliveries. Labor duration, cervical
      dilation, and uterine activity necessary to attain the active phase are reviewed.
      A practical definition of failed induction of labor is suggested.

PMID- 16885666
TI  - Oxytocin for induction of labor.
AB  - Oxytocin is the most common pharmacologic agent used for the induction and
      augmentation of labor. Oxytocin protocols can be divided into high-dose and low
      dose protocols depending on the initial dose and the amount and rate of
      sequential increase in dose. Despite the frequency with which oxytocin in used in
      clinical practice, there is little consensus regarding which protocol is most
      appropriate. The purpose of this chapter is to review the most current data
      concerning recommendations for the use of oxytocin in the induction of labor,
      including cases of intrauterine fetal demise and vaginal birth after cesarean.

PMID- 16885668
TI  - Vaginal misoprostol administration for cervical ripening and labor induction.
AB  - Intravaginal misoprostol has been shown to be an effective agent for cervical
      ripening and induction of labor. Vaginal application of misoprostol has been
      reported in over 9000 women worldwide and seems to have safety profile similar to
      that of endocervically and intravaginally administered dinoprostone. Concern
      arises with the use of higher doses of intravaginal misoprostol (50 mcg or more)
      and the association with uterine contractile abnormalities and for this reason,
      use of low-dose misoprostol regimen has been recommended by the American College
      of Obstetricians and Gynecologists. The recommendation is use of a 25-mcg dose of
      misoprostol inserted into the posterior vaginal fornix and repeated every 3 to 6
      hours as needed. Misoprostol administration to women with prior cesarean births
      seems to increase the likelihood of uterine scar disruption and should not be
      used in these women. There are reports of uterine rupture in women with unscarred
      uteri treated with vaginally applied misoprostol. Therefore, all patients need to
      be monitored adequately after misoprostol administration. Although there is a
      growing body of data regarding the ambulatory use of intravaginal misoprostol for
      cervical ripening, its use for this purpose cannot be recommended outside of
      investigational protocols at this time because of concerns for maternal and
      neonatal safety.

PMID- 16885667
TI  - Natural prostaglandins for induction of labor and preinduction cervical ripening.
AB  - Prostaglandin (PG) E2 has superseded all other natural prostaglandins for
      induction of labor and pre-induction cervical ripening. This evolution and its
      rationale are briefly described. PGE2 has been administered intravenously,
      orally, vaginally, endocervically, and extra-amniotically for induction of labor.
      All of these, except the intravenous route, have also been explored for pre
      induction cervical ripening. The distinction between formal induction and pre
      induction is not always clearly made with many studies pursuing both goals at
      once. Nevertheless, the effectiveness of PGE2 to achieve ripening and induction
      is currently beyond doubt. In women with unfavorable induction prospects PGE2
      results in lower rates of failed induction and higher rates of delivery within a
      reasonable interval than amniotomy and/or oxytocin. This also applies to women
      with prelabor rupture of the membranes, but the relative advantages of PGE2 over
      traditional methods are less clear for women with a favorable cervix. Vaginal
      administration of PGE2 has superseded virtually all other routes of PGE2
      administration except the endocervical route, which tends to give variable
      results depending on spillage from the endocervical canal. Doses and formulations
      of vaginal PGE2 with various gels, tablets, pessaries and slow release inserts
      have varied widely and continue to do so. There is currently no evidence for the
      superiority of one PGE2 preparation over another.

PMID- 16885669
TI  - Mechanical methods of cervical ripening and labor induction.
AB  - This article reviews the safety and efficacy of mechanical agents for cervical
      ripening. Hygroscopic dilators, balloon catheters, and devices designed for
      cervical ripening have all been shown to be safe and effective for cervical
      ripening. Mechanical agents are as efficacious as other agents for cervical
      ripening. However, there is no method that has been conclusively shown to improve
      mode of delivery or perinatal outcome. The advantages of preinduction cervical
      ripening with mechanical devices include low cost, low incidence of systemic side
      effects, and low risk of uterine hyperstimulation.

PMID- 16885670
TI  - Oral misoprostol administration for labor induction.
AB  - Using oral agents for induction of labor would reduce the need for repeated
      vaginal examinations; this is more acceptable to women and could reduce infection
      rates. A systematic review was conducted of 41 randomized trials comparing oral
      misoprostol to other induction agents. Oral misoprostol is effective at achieving
      vaginal delivery, and may have benefits over both vaginal and intracervical
      dinoprostone. Although it does not achieve vaginal delivery as quickly as vaginal
      misoprostol, the rates of hyperstimulation are lower when using comparable doses.
      As the primary consideration should be safety rather than speed, an oral regimen
      using a maximum of 50 mcg 4 hourly is recommended.

PMID- 16885672
TI  - Prior cesarean: a contraindication to labor induction?
AB  - In 2004, cesarean rates were the highest ever in the United States.
      Simultaneously, the vaginal birth after cesarean (VBAC) rate fell, largely a
      result of reports of uterine rupture associated with VBAC attempts. This chapter
      reviews the efficacy and safety of VBAC associated with labor induction.
      Mechanical and pharmacologic methods of labor induction (notably misoprostol) are
      associated with increased maternal and perinatal morbidity compared with
      spontaneous VBAC attempts. However, the absolute risks remain low. Labor
      induction is not contraindicated in women with a prior cesarean but sound
      judgment, clinical precautions and specific consent are required.

PMID- 16885671
TI  - Prelabor rupture of membranes at term: induction techniques.
AB  - The clinical management of premature rupture of membranes (PROM) at term has been
      a matter of considerable controversy. Management options have included expectant
      management or induction of labor with oxytocin, dinoprostone (PGE2), or
      misoprostol. Early studies suggested that immediate oxytocin induction of labor
      might reduce maternal and neonatal infections while increasing risk for cesarean
      section. The definitive TermPROM study found no difference in neonatal infections
      between immediate and delayed induction with oxytocin and PGE2. However, neither
      PGE2 nor delayed induction resulted in fewer cesarean sections than immediate
      oxytocin. Misoprostol offers several theoretical advantages over oxytocin in the
      setting of PROM at term. However, randomized trials to date have found no
      significant advantage for misoprostol administration compared with other agents
      for women with PROM.

PMID- 16885673
TI  - Elective induction of labor.
AB  - Induction of labor rates have more than doubled nationwide in the past 15 years.
      The increase in medically induced inductions was slower than the overall
      increase, suggesting that inductions for marginal or elective reasons rose more
      rapidly. Elective inductions seem to account for at least half of all inductions
      and 10% of all deliveries. Whether the experience of an elective induction is
      satisfactory to the patient, obstetrician, and intrapartum crew warrants more
      widespread attention. Cesarean rates are high for nulliparas undergoing an
      induction with an unfavorable cervix. Prospective studies are limited or
      nonexistent to recommend induction of labor for elective or marginal indications.
      Until more prospective work is performed, it will be difficult to evaluate the
      true impact of the elective induction of labor on population-wide cesarean
      delivery rates. Strategies for increased obstetrician awareness are proposed
      through practice guidelines and through clinical research trials.

PMID- 16885676
TI  - Food allergies: new labeling guidelines issued by the FDA.

PMID- 16885677
TI  - What CNAs need to know and why. Nutrition education for members of the health
      care team: part III.

PMID- 16885678
TI  - The CNA: a valuable part of the team.

PMID- 16885681
TI  - Teaching prioritization skills: a preceptor forum.
AB  - The Medical Specialty Preceptor Council of a large tertiary medical center
      selected prioritization as a theme to address with medical specialty registered
      nurse preceptors. Activities included exploration of the literature, personal
      reflection on preceptor experiences, and creation of a project that culminated in
      a preceptor forum. The forum included interactive poster stations staged for a
      drop-in session for preceptors. The stations were developed and staffed by
      Council members using research and ideas from colleagues.

PMID- 16885679
TI  - Education and practice collaboration: using simulation and virtual reality
      technology to assess continuing nurse competency in the long-term acute care
      setting.
AB  - Assessment of continuing competence of staff is a challenge for many healthcare
      organizations. There is no clear consensus as to what constitutes continuing
      competence or how to measure that competence. Methods for assessing continued
      competence of nurses are varied. A novel method, simulation and virtual reality
      technology, was used to assess the competency of nurses employed in long-term
      acute care hospitals in Louisiana. This article will describe the project which
      was the result of a collaborative effort between a large healthcare organization
      and a school of nursing.

PMID- 16885683
TI  - Educational opportunities for experienced staff: do they make a difference?
AB  - This study evaluates the impact of educational programs, such as Advanced Burn
      Life Support (ABLS), on the knowledge base of experienced burn nurses. A
      convenience sample of six clinical experts within a 21-bed southeastern burn
      center who had never taken ABLS participated. The quantitative findings display a
      high level of value and an increase in knowledge base. The results of this study
      suggest that nurses with high levels of experience will have an increase in
      knowledge and express value in continuing education curricula. Consequently, this
      study supports the necessity of educational programs for nurses with significant
      specialized experience.

PMID- 16885684
TI  - When new graduate nurses fail the NCLEX: what role can the hospital play?
AB  - New graduate nurses employed at a hospital who have failed the National Council
      Licensure Examination are in need of guidance. They are no longer a part of the
      academic system, and hospital educators are often at a loss as to how to assist
      them in successful completion of the licensing exam. This article provides
      information on how to support and guide the new graduate during this difficult
      time.

PMID- 16885687
TI  - Where do we fit and what should we do?

PMID- 16885685
TI  - Improving medication calculation skills of practicing nurses and senior nursing
      students: a pilot study.
AB  - Medication administration is an essential nursing competency as calculation
      difficulties can lead to serious medication errors. Nurses involved in staff
      education need to be aware of methods to assess for computation difficulty and
      develop strategies for nurses to improve their computation abilities. The
      purposes of this quasi-experimental pilot study were to assess the medication
      calculation skills of nurses and nursing students and to determine the
      effectiveness of teaching strategies aimed at improving these skills.

PMID- 16885686
TI  - The national post-baccalaureate graduate nurse residency program: a model for
      excellence in transition to practice.
AB  - The Chief Nursing Officers (CNOs) of the University HealthSystems Consortium
      (UHC) of Academic Hospitals desired to increase the numbers of baccalaureate
      graduate nurses hired by their facilities and provide a more consistent, uniform
      transition into practice for these graduate nurses. A partnership between the UHC
      CNOs and the American Association of Colleges of Nursing (AACN) led to
      establishing a National Post-Baccalaureate Graduate Nurse Residency Program. The
      structure, curriculum, and outcomes measures were developed and the program was
      implemented, with growth from six original pilot sites to 34 academic hospitals.
      Outcomes from the first year of program operation at these six sites show a high
      rate of retention, decreased stress by graduate nurses over time, improved
      organization and prioritization of care, and increased satisfaction in the first
      year of practice.

PMID- 16885689
TI  - Staff development through a patient safety lens.

PMID- 16885690
TI  - Diverticulitis: New Concepts and New Therapies. Proceedings of the Yale
      University workshop, December 2, 2005.

PMID- 16885691
TI  - What do we know about diverticular disease? A brief overview.
AB  - Diverticulosis and its complications, particularly diverticulitis, are extremely
      common in western countries. The major factor in the development of
      diverticulosis is a lack of adequate fiber intake. Diverticulitis may be
      complicated by abscess formation, fistula formation, peritonitis, or obstruction.
      Computed tomography scans are highly useful tools to plan appropriate care. Most
      cases of simple, uncomplicated diverticulitis respond to conservative therapy
      with bowel rest and antibiotics. Many controversies remain in the care of
      diverticulitis patients, including the optimal timing of surgery. One
      particularly interesting area of recent research examines the overlap of
      diverticulitis and inflammatory bowel disease, including the use of probiotics
      and mesalamine in diverticular disease.

PMID- 16885692
TI  - Case closed? Diverticulitis: epidemiology and fiber.
AB  - A major advance in understanding diverticular disease occurred decades ago with
      the epidemiologic association between fiber intake and the development of
      diverticular disease. This association has been well documented with
      investigations into the emergence of diverticular disease in underdeveloped
      countries where the disease had been virtually unknown before the adoption of a
      westernized diet, low in fiber. The high frequency of right-sided diverticular
      disease in Asian countries diverges from what is seen in the West. The
      physiologic effects of insoluble fiber has been well examined as well, increasing
      bulk and decreasing transit time, with a deficiency contributing to the high
      pressures implicated in the physiology which leads to diverticular disease.
      However, at most, 10% to 25% of individuals with diverticular disease will
      develop diverticulitis. Risk factors for symptomatic diverticular have been
      increasingly described in recent years with obesity and red meat intake being of
      particular importance, in addition to age. However, the known factors poorly
      identify those at increased risk and the predisposing pathophysiology is
      incompletely understood as well. Insoluble fiber, but not soluble fiber, has been
      viewed as the principal component which has been deficient in western diets and
      is the culprit which leads to the establishment of diverticular disease and in
      turn, diverticulitis. Soluble fiber and its effect on the intestinal flora is
      proposed as having significant influence on the development of diverticulitis.
      This understanding, if demonstrated, would have important implications for the
      primary and secondary prevention of diverticulitis.

PMID- 16885693
TI  - How inflammation changes neuromuscular function and its relevance to symptoms in
      diverticular disease.
AB  - Diverticulosis is largely asymptomatic but recent evidence suggests that episodes
      of acute diverticulitis double the risk of subsequently suffering from recurrent
      noninflammatory pain. Numerous animal models demonstrate how inflammation is
      followed by circular muscle hypertrophy, abnormalities of innervation, and
      increased sensitivity to cholinergic agents. There is also an impairment of
      norepinephrine and acetylcholine release and damage to nitrergic neurons. These
      changes are also associated with visceral hypersensitivity. Many of the features,
      including visceral hypersensitivity are also seen in symptomatic patients with
      diverticulosis. The trinitrobenzene sulfonic acid colitis model demonstrates that
      inflammation is followed by long lasting increases in tachykinin and other
      neuropeptide immunoreactivity. These changes occur both in the mucosa and
      myenteric plexus and parallel changes seen in resections and mucosal biopsies in
      diverticular patients. These neural abnormalities may be responsible for the
      visceral hypersensitivity, which explains why symptoms correlate poorly with
      objective abnormalities such as intraluminal pressure or motor patterns.
      Treatment of visceral hypersensitivity might be more effective than current
      therapies that often leave pain unaltered.

PMID- 16885694
TI  - A hypothesis: is diverticulitis a type of inflammatory bowel disease?
AB  - It is accepted by epidemiologists that diverticula formation in the colon is
      related to a deficiency in dietary fiber intake, but the cause of acute
      diverticulitis remains unknown. A hypothesis is presented that acknowledges from
      the literature that fiber deficiency is also related to an altered intestinal
      microecology with a change in the bacterial flora. It is hypothesized that the
      change in the flora with a decrease in their influence on the immune process
      permits a low-grade chronic inflammation in the mucosa, which is the first step
      in developing an acute infection of diverticula or diverticulitis. There is some
      evidence that the low-grade chronic inflammation is present in subjects with
      diverticula, which is the forerunner of acute diverticulitis. This hypothesis is
      strengthened by early reports that anti-inflammatory mucosal agents such as
      mesalamine and immune process regulators such as probiotics may improve
      diverticulitis.

PMID- 16885695
TI  - The pathology of diverticulosis: classical concepts and mucosal changes in
      diverticula.
AB  - Left-sided diverticular disease affects upwards of 50% of the population over the
      age of 60 years in western countries and is becoming more common as the
      population ages. Studies from the 1960s to 1980s related its occurrence to the
      use of low fiber diets, and to the prolonged colonic transit time and increased
      intraluminal pressure associated with low-volume stools. Pulsion diverticula
      (pseudodiverticula) emerge through the muscularis propria of the left colon at
      points of penetration of the vasa recta that supply the submucosa and mucosa.
      Cardinal features of the sigmoid colon in diverticular disease are abnormalities
      of the muscularis propria, including thickening and elastosis of the teniae,
      shortening of the bowel, and thickening and folding of the circular muscle with
      the development of transverse semilunar ridges between the mesenteric and
      antimesenteric teniae. Complications of diverticular disease such as hemorrhage,
      diverticulitis, peridiverticular abscess, fistula, and perforation are well
      recognized.

PMID- 16885696
TI  - Segmental colitis associated with diverticular disease and other IBD look-alikes.
AB  - Segmental colitis associated with diverticular disease is an inflammatory
      disorder that bears close clinical and histopathologic similarities to idiopathic
      inflammatory bowel disease. Comparison with other inflammatory bowel disease-like
      disorders, such as blind-ended pouches in ulcerative colitis, chronic
      granulomatous appendicitis, and delayed-surgery appendicitis, affords intriguing
      analogies and potential clues to its pathogenesis.

PMID- 16885697
TI  - Diagnosis and management of acute diverticulitis.
AB  - Although the diagnosis of acute diverticulitis is somewhat standardized, the
      scientific evidence and basis for treatment has been questioned. For years,
      medical and surgical management of acute diverticulitis has been based on the
      theory that more than 2 significant attacks of diverticulitis would lead to the
      recommendations of surgical resection. This should be questioned and further
      investigated with prospective randomized trials. Only a small number of well
      published articles support the surgical management with good scientific data.
      Although our ability to take a history and skill of physical examination has not
      changed, the use of improved technology such as high-speed computerized axial
      tomography has afforded us the ability to make earlier and more accurate
      diagnoses. This may further allow us to standardize treatment and study outcomes.
      The time has come to further investigate and justify this management. It is
      possible that only the most critical situations may necessitate an operation.
      Clearly, the age group less than 40 years, as well as the immunocompromised,
      steroid-dependent, diabetic, and transplant patients, seem to be at greater risk
      with increased morbidity if not treated early and aggressively. And those
      individuals who present with perforation or compromised obstruction most likely
      will continue to need emergent intervention. We should try to set the rules by
      evidence-based medicine, while remaining within the confines of excellent and
      cost-effective care.

PMID- 16885698
TI  - Diagnosis and treatment of chronic and recurrent diverticulitis.
AB  - In Western countries the prevalence of diverticular disease has increased over
      the past century. Although, most patients remain asymptomatic, among those who
      experience an attack of diverticulitis, one-third will have recurrent symptoms,
      and a further third will have a subsequent episode. The indications for surgery
      after treatment of acute diverticulitis is still under debate. Uncomplicated
      disease less commonly as thought, progresses to a life threatening situation such
      as free perforation. Among those who develop complicated diverticulitis, it is
      often their first presentation. Fistula to the urinary tract often require
      surgery; however, complicated disease such as an abscess or phlegmon can be
      managed conservatively and subsequent surgery is selective depending on the
      recovery from the initial episode. Patients with chronic diverticular disease
      (persistent pain in the absence of inflammation) have greatly improved quality of
      life with surgery. The question of greater virulence of disease among young
      patients may no longer be true and recommendations for surgery may parallel that
      of older patients. Immunocompromised patients should have definitive surgical
      therapy early on in the course of the disease. Right-sided disease remains
      uncommon in the Western world and a conservative approach in the absence of free
      perforation is recommended. In right-sided disease and in young patients,
      misdiagnosis is common. In the elective setting, a laparoscopic approach is
      rapidly becoming preferred because of less morbidity and shorter hospital stay.
      The treatment of diverticular disease is rapidly undergoing reevaluation, and
      novel therapies and increased conservative approaches are evolving. Prospective
      randomized trials are needed, but remain difficult owing to the uncertain natural
      history of the disease.

PMID- 16885699
TI  - The metabolism of mesalamine and its possible use in colonic diverticulitis as an
      anti-inflammatory agent.
AB  - 5-Aminosalicylic acid (5-ASA) is the mainstay of therapy for inflammatory bowel
      disease (IBD), particularly ulcerative colitis. 5-ASA is the active moiety in
      sulfasalazine, which was initially developed for the treatment of rheumatoid
      arthritis more than 60 years ago, by linking 5-ASA with sulfapyridine Because
      many of the side effects related to sulfasalazine were found to be due to
      sulfapyridine, several drugs that contain 5-ASA, and lack the side-effect profile
      of sulfasalazine, have been developed during the last 2 decades. These drugs have
      proven to be quite effective in treating mild-to-moderate symptoms of IBD, as
      well as inducing and maintaining remission. Although they exert anti-inflammatory
      effects, their exact mechanism of action remains elusive. Nonetheless, their
      success in treating IBD has led to studies using this class of drugs for novel
      indications. Several recent studies have evaluated the use of 5-ASA drugs
      (mesalamine) for the treatment of uncomplicated acute diverticulitis. In this
      review, we will briefly discuss the development of 5-ASA releasing drugs, their
      metabolism, side effects, indications, mechanisms of action, and the rationale
      for the clinical use of mesalamine in colonic diverticulitis.

PMID- 16885700
TI  - Use of mesalazine in diverticular disease.
AB  - Diverticular disease includes a spectrum of conditions sharing the underlying
      pathology of acquired diverticula of the colon: symptomatic uncomplicated
      diverticular disease, recurrent symptomatic uncomplicated diverticular disease,
      and complicated diverticular disease. Goals of therapy in diverticular disease
      should be to improve symptoms and to prevent recurrent attacks in symptomatic
      uncomplicated diverticular disease, and to prevent the complications of disease
      such as diverticulitis. Inflammation seems to play a key role in all forms of the
      disease. This is the rationale for the use of anti-inflammatory drugs such as
      mesalazine. Inflammation in such diseases seems to be generated by a heightened
      production of proinflammatory cytokines, reduced anti-inflammatory cytokines, and
      enhanced intramucosal synthesis of nitric oxide. The mechanisms of action of
      mesalazine are not yet well understood. It is an anti-inflammatory drug that
      inhibits factors of the inflammatory cascade (such as cyclooxygenase) and free
      radicals, and has an intrinsic antioxidant effect. Some recent studies confirm
      the efficacy of mesalazine in diverticular disease both in relief of symptoms in
      symptomatic uncomplicated forms and in prevention of recurrence of symptoms and
      main complications.

PMID- 16885701
TI  - Probiotics and their use in diverticulitis.
AB  - Probiotics are live microorganisms that when ingested affect the intestinal
      microbial flora and benefit the health of the host. Probiotics have been shown to
      have a positive effect on various gastrointestinal and other conditions; however,
      the beneficial effect of probiotics on treating diverticulitis and diverticular
      disease has not yet been clearly demonstrated. In this paper, the theoretical
      framework for using probiotics to prevent or treat diverticular disease is
      reviewed, and two preliminary studies on the use of probiotics for maintenance of
      remission of uncomplicated diverticular disease are briefly summarized.

PMID- 16885703
TI  - Increasing the yield of EEG.
AB  - The EEG is the most common neurodiagnostic test performed to evaluate patients
      with suspected seizures. The majority of EEGs are requested in patients because
      of suspected seizures or for seizure management. It is unlikely that the
      patient's usual spell will be recorded during a routine EEG. Therefore, several
      activation techniques have been used in clinical EEG to help increase the
      occurrence of interictal epileptiform abnormalities, which are highly correlated
      with the diagnosis of a seizure disorder. EEG laboratories have long employed
      these techniques, which include hyperventilation, intermittent photic
      stimulation, sleep, and sleep deprivation. However, despite being utilized in
      routine clinical EEGs for decades, a number of differing views on the usefulness
      and indications for these procedures exist. This review will evaluate these
      procedures and review their history, technique, effectiveness, controversies, and
      unanswered questions.

PMID- 16885704
TI  - Ambulatory EEG telemetry: how good is it?
AB  - When someone asks the question, how good is ambulatory EEG telemetry, there is no
      correct answer. There are many manufacturers of ambulatory EEG technology. Each
      device has its own strengths and weaknesses. What one is really interested in
      when one asks such a question needs to be defined in terms of expectations and
      technical capabilities for the piece of equipment under discussion. Systems exist
      or can be easily modified to be as sophisticated as the best of the inpatient
      units. However, is that level of sophistication needed for the ambulatory based
      recordings? Again, the answer to that is dependent on the ordering physician's
      expectations. Below is a discussion of the different clinical expectations that
      are frequently encountered and the needed requirements for an ambulatory system
      to properly address them.

PMID- 16885705
TI  - Drug effects on EEG.
AB  - Although excess beta activity and a mild theta increase may be the most common
      EEG alterations associated with medication, more remarkable changes may also
      appear. Although changes such as diffuse delta, triphasic waves, bisynchronous
      spikes or polyspikes, burst suppression or electrocerebral inactivity may
      indicate a dismal prognosis under many circumstances; these patterns may fully
      resolve to a normal EEG if drug administration is the unique or principal cause.

PMID- 16885706
TI  - The EEG in selected generalized seizures.
AB  - This article reviews the ictal and interictal EEG findings associated with a
      select group of generalized seizures. These include absence seizures, myoclonic
      seizures seen in juvenile myoclonic epilepsy, idiopathic generalized tonic clonic
      seizures, infantile spasms, and atypical absence, tonic, and atonic seizures
      associated with the Lennox Gastaut syndrome.

PMID- 16885707
TI  - EEG of partial seizures.
AB  - EEG remains the primary technique in the diagnosis, characterization, and
      localization of partial seizures. This review examines the significance and
      character of interictal epileptiform abnormalities, periodic lateralized
      epileptiform discharges, and ictal patterns in patients with partial epilepsy.
      Interictal epileptiform discharges are common and assist in the diagnosis and
      localization of partial seizures. Fortunately, true "false positive" EEGs with
      focal epileptiform abnormalities are distinctly rare. Periodic lateralized
      discharges have characteristics of both interictal and ictal activity and are an
      area of controversy as to their clinical significance. Ictal patterns in partial
      seizures are variable, with the most distinctive features seen in seizures from a
      mesial temporal lobe origin. The unifying EEG feature of a partial seizure is in
      its evolution. A partial seizure begins with a clear delineation of the onset of
      activity that is distinct from the preceding background, followed by an evolution
      of this activity in both frequency and amplitude and terminating with an
      identifiable cessation of the rhythmic pattern that merges again into the
      background activity.

PMID- 16885708
TI  - The EEG in nonepileptic seizures.
AB  - Nonepileptic seizures are episodes that resemble seizures but are not epileptic.
      The importance of EEG in the diagnosis of NES is that misread (overread) EEGs are
      an important contributor to the misdiagnosis of epilepsy. About 20% to 30% of
      patients with refractory "seizures" seen at epilepsy centers have been
      misdiagnosed, and the vast majority have psychogenic nonepileptic seizures
      (PNES). Many such patients have had previous EEGs interpreted as epileptiform.
      These misdiagnoses based on EEG are easily perpetuated, complicate management,
      and adversely affect outcome. The reasons for the overinterpretation of EEGs
      include the common misconception that phase reversals indicate abnormalities and
      not applying strict criteria to make sharp transients epileptiform. The diagnosis
      of PNES typically begins with a clinical suspicion and then is confirmed with EEG
      video monitoring. However, ictal EEG may be negative in some partial seizures and
      may be uninterpretable because of artifacts. Movements can generate rhythmic
      artifacts that mimic an electrographic seizure. Analysis of the ictal semiology
      (i.e., video) is at least as important as the ictal EEG. Provocative techniques,
      activation procedures, or "inductions" can also be useful for the diagnosis of
      PNES.

PMID- 16885709
TI  - Value and limitations of seizure semiology in localizing seizure onset.
AB  - Seizure semiology has been the foundation of clinical diagnosis of seizure
      disorders. This article discusses the value and the limitations of behavioral
      features of seizure episodes in localizing seizure onset. Studies have shown that
      some semiologic features of seizures are highly accurate in the hemispheric
      lateralization and lobar localization of seizures. There is good agreement
      between blinded reviewers in lateralizing video-recorded seizures in temporal
      lobe and extratemporal lobe epilepsies. However, seizure semiology alone should
      not be used to determine the site of seizure onset. Each semiologic feature may
      falsely localize seizure onset. Seizure semiology in some patients may signify
      the site of seizure propagation rather than origination. Moreover, seizure
      semiology may not be as reliable in multifocal epilepsies as it is in unifocal
      epilepsies. Many semiologic features of seizures of adults are often missing in
      seizures of children. Seizure semiology should be analyzed and integrated with
      EEG and neuroimaging data to localize the seizure focus. A sample of the recorded
      seizures should be shown to the patient's relatives or friends to verify that it
      is representative of habitual seizures.

PMID- 16885710
TI  - Electric source imaging in frontal lobe epilepsy.
AB  - The objective of this study was to determine the validity of interictal spike
      (IIS) source localization in frontal lobe epilepsies (FLE) using
      stereoelectroencephalography as a validating method. Ten patients with drug
      resistant FLE were studied with high-resolution EEG and
      stereoelectroencephalography. Sixty-four scalp channels, a realistic head model,
      and different algorithms were used. For each patient, the intracerebral
      interictal distribution was studied and classified into one of three groups:
      lateral, medial, and mixed (latero-medio-basal). Surface IIS were abundant or
      subcontinuous for 8 of 10 FLE patients. In lateral and medial groups,
      intracerebral interictal activities were accurately localized. In the mixed
      group, source localizations designated a part of the intracerebral interictal
      distribution. A high degree of source localization accuracy is obtained in FLE.
      False-positive results were never obtained, but the extent of interictal activity
      could be underestimated by source localization results. Geometrical and
      cytoarchitectonic characteristics of the generator appear crucial to explain why
      medial frontal IIS (anterior para-cingulate gyrus and anterior cingulate gyrus)
      may be localizable whereas only the lateral orbitofrontal IIS seems to be
      localizable.

PMID- 16885711
TI  - EEG changes in a patient with steroid-responsive encephalopathy associated with
      antibodies to thyroperoxidase (SREAT, Hashimoto's encephalopathy).
AB  - A 56-year-old woman presented with an acute confusional state and moderate global
      aphasia. Thyroperoxidase antibody level was elevated (3,890 IU/mL) and SREAT was
      diagnosed. MRI findings were normal. Cerebrospinal fluid examination revealed
      only a mildly increased protein. The initial electroencephalogram EEG showed
      slowing and markedly decreased amplitude over the left hemisphere and left
      temporal sharp waves. An EEG performed after treatment with intravenous steroids
      showed a significant improvement of the background slowing, which correlated with
      clinical improvement. One week later, the patient had an episode of forced head
      turning and fencing posture to the right. The EEG shortly afterward showed
      slowing and a decreased amplitude over the right hemisphere. Continuous EEG
      monitoring was performed at the time of steroid treatment. Again, there was a
      significant improvement of the EEG after this treatment that correlated with the
      clinical condition. SREAT is characterized by fluctuations in mental status and
      variable EEG findings. These patients often show an excellent clinical
      improvement to immunosuppressive therapy, including corticosteroids. This case
      report documents the dramatic clinical and EEG improvement with steroid therapy.

PMID- 16885713
TI  - Neurophysiologic studies in early-onset cerebellar ataxia.
AB  - The discovery of the gene for Friedreich's ataxia (FRDA) has not only broadened
      the FRDA phenotype, but has also identified patients with early-onset cerebellar
      ataxia who resemble FRDA clinically but who do not carry a mutation in the
      frataxin gene. In order to identify subgroups that may represent a uniform
      underlying disorder, we performed neurophysiologic studies, including nerve
      conduction studies, electromyography, and transcranial magnetic stimulation, in
      15 patients with a slowly progressive, unexplained, early-onset cerebellar ataxia
      (EOCA). In addition, sural nerve biopsy data were available in four patients. The
      neurophysiologic data identified three distinctive groups of EOCA patients: three
      patients with normal motor and sensory conduction velocities and borderline
      sensory amplitudes (group 1); three patients with a mild, predominantly motor,
      axonal neuropathy (group 2); and nine patients with a highly uniform syndrome
      characterized by pyramidal features and a severe sensory and motor axonal
      neuropathy (group 3). We conclude that, on the basis of neurophysiologic studies,
      distinctive groups of patients with EOCA can be delineated, and that
      differentiation between patients with EOCA can be useful for differential
      diagnostic consideration. Whether this splitting also reflects a fundamental
      phenotypic difference and, therefore, may direct future DNA studies, remains to
      be established.

PMID- 16885712
TI  - Assessing the temporal reproducibility of human esophageal motor-evoked
      potentials to transcranial magnetic stimulation.
AB  - BACKGROUND: Although the electrophysiological properties and reproducibility of
      somatic limb motor evoked potentials (MEPs) to transcranial magnetic stimulation
      (TMS) are well characterized, little is known about the reproducibility of MEPs
      for viscerosomatic structures such as the esophagus. AIM: To determine the
      temporal reproducibility of esophageal MEPs to TMS. METHODS: MEPs to TMS were
      recorded from the proximal esophagus, using a swallowed catheter housing a pair
      of electrodes, in eight healthy subjects at five stimulus intensities (SI) (motor
      threshold [MT] to 20% above MT). For each SI, 20 consecutive TMS stimuli at 5
      second intervals were delivered over a single scalp site (dominant hemisphere at
      site exhibiting MT at lowest SI) and repeated 40 and 80 minutes thereafter. MEP
      amplitudes and latencies were measured, and means were sequentially calculated
      for each SI and then log-transformed. The repeatability coefficients (RC) for the
      three time points were calculated across each set of 20 stimuli and presented as
      an exponential ratio. RESULTS: Best RC (amplitude/latency) were achieved at 120%
      SI relative to MT, being 1.8/1.2 (optimal = 1.0). For lower intensities of 115%,
      110%, 105%, and 100% SI, the RC were 2.1/1.2, 2.1/1.1, 2.4/1.2, and 2.6/1.4,
      respectively. For all SI, the greatest reductions in RC occurred over the first
      10 stimuli, with little additional gain beyond this number. CONCLUSIONS:
      Latencies of esophageal MEP to TMS across intensities are highly reproducible,
      whereas amplitudes are more stimulus intensity-dependent, being most reliable and
      reproducible at the highest stimulus strengths. SIGNIFICANCE: Using careful
      parameters, TMS can be used reliably in future studies of viscerosomatic
      structures, although the size of the response variability needs to be taken into
      account when assessing changes in cortico-fugal activity.

PMID- 16885714
TI  - Pharmacokinetics and pharmacotherapy of thionamides in pregnancy.
AB  - Hyperthyroidism occurs in approximately 1 in every 1000 to 2000 pregnancies.
      Although the signs and symptoms of the disease are similar in the pregnant and
      nonpregnant patient, the complications of hyperthyroidism can have even more
      profound consequences for the mother and fetus during gestation. These include
      maternal heart failure, preeclampsia, miscarriage, and preterm labor; as well as
      fetal loss and low birth weight. Furthermore, thyroid function and laboratory
      testing for hyperthyroidism are altered in pregnancy. The gestational increase in
      thyroid size, increased thyroid-binding globulin levels, increased serum total T4
      and total T3 levels, and decreased thyroid stimulating hormone levels often
      confuses the evaluation of the thyroid status in pregnancy. Worldwide, the
      thionamides-propylthiouracil, methimazole, and carbimazole-have been used in
      pregnancy for the treatment of hyperthyroidism. However, propylthiouracil has
      been the drug of choice in the United States because it is believed to have less
      potential to induce fetal/neonatal hypothyrodism, to cross the placenta and into
      breast milk to a lesser degree, and to be less teratogenic than methimazole or
      carbimazole. None of the above have been substantiated in more recent studies.
      The pharmacokinetics of the thionamides in the pregnant and nonpregnant states,
      as well as the pharmacotherapeutic recommendation for hyperthyroidism will be
      reviewed.

PMID- 16885715
TI  - Sensitive, high throughput HPLC-MS/MS method with on-line sample clean-up for
      everolimus measurement.
AB  - A new HPLC-MS/MS method for everolimus measurement was developed that includes
      the following features: small sample volume, short run time, fast, simple and
      cost-efficient sample preparation, assessment of performance of two internal
      standards (IS), SDZ RAD 223-756 and ascomycin and comparison of the method with
      an HPLC-MS/MS reference method. The authors established a multiple reaction
      monitoring positive ion HPLC-MS/MS method with on-line extraction and sample
      cleanup. This procedure includes: an API 2000 triple quadrupole mass spectrometer
      with turbo-ion spray, built-in Valco switching valve, an HPLC system; guard
      column; a Nova-Pak C18 analytical column; washing solution, methanol:30 mM
      ammonium acetate pH 5.1 (80:20); eluting solution, methanol:30 mM ammonium
      acetate pH 5.1 (97:3); flow rate 0.8 mL/min; and a run time of 2.8 minutes. The
      first and third quadrupoles were set to detect the ammonium adduct ion and a high
      mass fragment of everolimus (m/z 975.5-->908.5), and two ISs: SDZ RAD 223-756
      (m/z 989.8-->922.8) and ascomycin (m/z 809.5-->756.5). The LLOQ was 1.0 microg/L
      for everolimus using either IS. Between day precision ranged from 3.1% to 5.7%
      for SDZ RAD 223-756 and 6.0% to 8.6% for ascomycin using spiked blood with
      everolimus concentrations 2.0 to 25.0 microg/L. Absolute recoveries using spiked
      samples over the range of 2.5 to 25 mug/L averaged 77.3% (SDZ RAD 223-756) and
      76.8% (ascomycin). No matrix effect on everolimus was demonstrated based on the
      mean observed signal detection of 98.6% (SDZ RAD 223-756) and 105% (ascomycin).
      Comparison of everolimus concentrations obtained using this method with two
      internal standards with a reference laboratory demonstrated that the mean
      everolimus concentration obtained with ascomycin was statistically different
      (lower) than results with the reference method and the method that used SDZ RAD
      223-756 as the internal standard gave equivalent results compared with the
      reference method.

PMID- 16885716
TI  - Is microparticle enzyme-linked immunoassay (MEIA) reliable for use in tacrolimus
      TDM? Comparison of MEIA to liquid chromatography with mass spectrometric
      detection using longitudinal trough samples from transplant recipients.
AB  - In the larger transplant centers where technical expertise is available, liquid
      chromatography with mass spectrometric detection (LC-MS) for tacrolimus
      therapeutic drug monitoring is replacing the popular microparticle enzyme-linked
      immunoassay (MEIA) as a cost-effective alternative technology. As more labs
      convert to LC-MS, the accuracy, precision, selectivity, and sensitivity of the
      tacrolimus MEIA are being challenged, using data from large populations of
      clinical samples. However, little attention has been paid to how the results of
      particular procedures may differ within and among individual patients and to how
      such differences may relate to patients' characteristics or to relevant
      biochemical parameters. So, after validation of an LC/MS procedure and
      verification of an LC/MS/MS procedure, the author analyzed 552 serial trough
      blood tacrolimus samples, collected from 38 patients over a 3-month period, by
      controlled MEIA and LC-MS procedures. Corresponding hematocrit and serum albumin
      level data were obtained. In an attempt to investigate whether the observations
      of others who studied population-based data could be illustrated for individuals,
      longitudinal data from several patients were plotted to visually elucidate any
      relations between the tacrolimus concentration and biochemical data. Finally
      tacrolimus concentration, hematocrit, and serum albumin data were compared using
      data stratified by transplant type, in-/outpatient status, male/female gender, or
      period elapsed since transplant surgery. The validated/verified LC-MS procedures
      were shown to be much better controlled than the MEIA during the 3-month parallel
      comparison study period. The longitudinal data of several individuals who
      experienced wide changes in the biochemical parameters clearly illustrated the
      relation between the difference in tacrolimus concentrations determined by MEIA
      and LC-MS and hematocrit (and sometimes albumin). Differences between the MEIA-
      and LC-MS-determined tacrolimus concentration data were strongly correlated to
      transplant type, in-/outpatient status, gender, time elapsed since liver
      transplant surgery, hematocrit, and weakly to serum albumin levels. In summary,
      the LC-MS methods provide highly reliable and reproducible estimates of
      tacrolimus concentrations, whereas the performance of MEIA technology did not
      provide reliable long-term performance for longitudinal therapeutic drug
      monitoring of tacrolimus because it was effected by several inherent demographic
      factors and by factors that can change over time in transplant recipients.

PMID- 16885717
TI  - Fully automated analytical method for mycophenolic acid quantification in human
      plasma using on-line solid phase extraction and high performance liquid
      chromatography with diode array detection.
AB  - We have developed a new fully automated method for mycophenolic (MPA) acid
      quantification in plasma to optimize therapeutic drug monitoring of tranplant
      patients. This method involved solid-phase extraction on disposable extraction
      cartridges and reversed-phase high-performance liquid chromatography with diode
      array detection. Solid-phase extraction was performed automatically by an
      automated sample with extraction catridges system. After washing, MPA was eluted
      from the cartridge onto a Chromolith RP-18e column. MPA and the internal standard
      were detected at 306 nm. The retention time of MPA was 6.3 minutes. The developed
      method was linear from 0.2 to 20 microg/mL. The limit of quantification was 0.2
      microg/mL. The method showed a good precision with intraday and interday
      variation coefficient less than 6%. The intraday accuracy ranged from 97.6% to
      100.4% and the interday accuracy varied from 97.1% to 100.8%. The extraction
      efficiency was greater than 90%. This method is simple and shows a good
      specificity with respect to commonly co-prescripted drugs.

PMID- 16885718
TI  - Determination of tipranavir in human plasma by reverse phase liquid
      chromatography with UV detection using photodiode array.
AB  - Tipranavir has recently received accelerated approval from the FDA. The initial
      clinical use of tipranavir will be for patients with prior virologic failure with
      the presence of key HIV-1 protease inhibitor mutations. In Phase III trials
      patients with greater virologic response also had higher trough tipranavir
      concentrations (BI product information 2005). In addition, hepatotoxicity was
      concentration-related with a higher incidence in those patients exceeding a
      trough plasma concentration of 48.2 microg/mL (80 microM). Therefore, tipranavir
      may be an HIV-1 protease inhibitor for which therapeutic drug monitoring (TDM)
      may be helpful in optimizing outcomes. To quantitate tipranavir concentrations in
      human plasma, a method using reversed phase high performance liquid
      chromatography (RP-HPLC) was validated. Detection was effected using a photodiode
      array detector, scanning at a wavelength of 254 nm. This method allows for
      detection of tipranavir to a lower limit of quantitation of 0.390 microg/mL with
      an interday variation in control value ranging from 2.9 to 4.6%. The method is
      being used in a clinical therapeutic drug monitoring program that is ongoing in
      our laboratory.

PMID- 16885719
TI  - Full validation of an analytical method for the HIV-protease inhibitor atazanavir
      in combination with 8 other antiretroviral agents and its applicability to
      therapeutic drug monitoring.
AB  - Because HIV medications are used in combination, it is important to develop
      multiplex assays to streamline the therapeutic drug monitoring process and
      provide rapid turnaround. This article reports full validation of an analytical
      method that combines atazanavir with 6 HIV-protease inhibitors (indinavir,
      amprenavir, saquinavir, nelfinavir, ritonavir, and lopinavir) and 2 nonnucleoside
      reverse transcriptase inhibitors (nevirapine and efavirenz). Using 200 microL of
      plasma and a simple liquid-liquid extraction method, this analytical method
      achieved a clean baseline and high extraction efficiencies (90.0% to 99.5%). A
      Zorbax C-18 (150 x 4.6 mm, 3.5 microm) analytical column was used along with a 27
      minute linear gradient elution of the mobile phase to provide sharp peaks at 210
      nm. This method was validated over a range of 25 to 10,000 ng/mL and is accurate
      (90.4% to 110.5%) and precise (precision within a day and between days ranged
      from 2.3% to 8.3%). Because this method is simple and inexpensive, it may have
      applicability in countries with low resources.

PMID- 16885720
TI  - Sensitive determination of itraconazole and its active metabolite in human plasma
      by column-switching high-performance liquid chromatography with ultraviolet
      detection.
AB  - A simple and sensitive column-switching high-performance liquid chromatographic
      method for the simultaneous determination of itraconazole (ITZ) and its active
      metabolite, hydroxyitraconazole (HIT) in human plasma is described. ITZ, HIT, and
      an internal standard, R051012, were extracted from 1 mL of alkalinized plasma
      sample using n-heptane-chloroform (60:40, vol/vol). The extract was injected onto
      column I (TSK precolumn BSA-ODS/S, 5 microm, 10 x 4.6 mm ID) for clean-up and
      column II (Develosil C8-5 column, 5 microm, 150 x 4.6 mm ID) for separation. The
      mobile phase consisted of phosphate buffer-acetonitrile (68:32 vol/vol, pH 6.0)
      for clean-up and phosphate buffer-acetonitrile (35:65 vol/vol, pH 6.0) for
      separation. The peaks were monitored with an ultraviolet detector set at a
      wavelength of 263 nm, and total time for chromatographic separation was about 24
      minutes. The validated concentration ranges of this method were 3 to 500 ng/mL
      for ITZ and 3 to 1000 ng/mL for HIT. Mean recoveries were 59.7% for ITZ and 72.8%
      for HIT. Intraday and interday coefficients of variation were less than 4.6% and
      5.0% for ITZ, and 4.6% and 4.9% for HIT at the different concentrations. The
      limit of quantification was 3 ng/mL for both ITZ and HIT. This method was
      suitable for therapeutic drug monitoring of ITZ and HIT, and was applied to
      pharmacokinetic studies in human volunteers.

PMID- 16885721
TI  - Therapeutic drug monitoring for dose individualization of Cisplatin in testicular
      cancer patients based upon total platinum measurement in plasma.
AB  - Cisplatin (CDDP) is an anticancer agent widely used in testicular cancer, for
      which pharmacokinetic (PK)/pharmacodynamic relationships have usually been based
      upon measurement of its unbound fraction in plasma. Because it has been shown
      that free CDDP clearance can be related to patient's body surface area (BSA),
      dosage is mostly adjusted a priori using only this single parameter, with mixed
      results for accurately predicting CDDP exposure and reducing toxicities. In
      contrast, the authors present here an original, 5-day continuous infusion
      schedule, coupled to a daily Bayesian adaptive dosing with feedback strategy,
      based upon the rapid assay of total, rather than free, CDDP in plasma. Nineteen
      patients (66 therapeutic courses) were treated with platinum-based combinational
      therapy. Plasma samples were analyzed to allow real-time Bayesian estimation of
      individual PK parameters with subsequent prospective dose adjustment in order to
      reach a target Cmax (Cend) of 1.95 mg/L of total platinum. Performance of the
      Bayesian dosing method was evaluated by comparing target Cmax with achieved Cmax.
      The mean+/-SD Cmax achieved was 1.93+/-0.16 mg/L. No statistically significant
      difference was observed between experimental and target values (P>0.05, t test),
      and Cend achievement was done with an overall 6.6% precision, a performance to be
      compared with the initial 54% interpatient variability observed in CDDP
      clearance. A nonlinear mixed effect model population PK analysis was subsequently
      performed to identify retrospectively the covariates associated with PK
      parameters of total CDDP. It showed a good correlation (r=0.84, P=0.004) between
      total platinum clearance and therapeutic course number. A weaker correlation
      (r=0.59) was found between BSA and total CDDP clearance and, importantly, no
      additional relationship was established with BSA when successive therapeutic
      courses, and not only the first one, were considered. This highlights the
      critical importance of total drug accumulation on CDDP pharmacokinetics when
      several infusions are to be administered in a row and, therefore, the need for
      real-time dose individualization that takes into account the course number,
      rather than BSA. Finally, doses of CDDP administered during each course were
      significantly higher (+20%, P<0.01) than the ones classically normalized with
      BSA, thus leading to an overall greater drug exposure in the patients. It is
      noteworthy that despite these markedly higher doses, little severe toxicity was
      reported, and all of the patients presented in this study were still alive and
      disease free after a follow-up of up to 15 years.

PMID- 16885722
TI  - Estimating time of last oral ingestion of cannabis from plasma THC and THCCOOH
      concentrations.
AB  - Estimating the time of last cannabis use is important in assessing possible
      impairment of drivers involved in accidents, in verifying accuracy of court
      testimony and in the future, helpful in therapeutic monitoring of cannabis
      agonists. In 1992, Huestis et al developed model 1, based on plasma Delta
      tetrahydrocannabinol (THC) concentrations, and model 2, on plasma 11-nor-9
      carboxy-Delta(9)-tetrahydrocannbinol/THC ratios, that predicted 95% confidence
      intervals for time of last cannabis use. These models seemed to be valuable when
      applied to the small amount of data from published studies of oral ingestion, a
      route of administration more popular with the advent of cannabis therapies. A
      study was designed to further validate the models after oral ingestion of THC,
      and to determine whether they could predict last usage after multiple oral doses.
      Eighteen subjects in IRB-approved studies participated after providing informed
      consent. Each of 12 subjects in one group received a single 10 mg oral dose of
      dronabinol (synthetic THC). In another protocol, 6 subjects received 4 different
      oral daily doses, divided into thirds and administered with meals for 5
      consecutive days. There was a 10-day washout period between each dosing regimen.
      Daily doses were 0.39, 0.47, and 14.8 mg THC in hemp oil and 7.5 mg dronabinol.
      Blood specimens were collected throughout the study and analyzed for plasma THC
      and 11-nor-9-carboxy-Delta(9)-tetrahydrocannbinol by gas chromatography/mass
      spectrometry with limits of quantification (LOQs) of 0.5 and 1.0 ng/mL,
      respectively. Actual times between ingestion of THC and blood collection spanned
      0.5 to 16 hours. All plasma specimens with analyte concentrations >LOQ (n=90)
      were evaluated. Models 1 and 2 correctly predicted time of last THC ingestion for
      74.4% and 90.0% of plasma specimens, respectively. 96.7% of predicted times were
      correct with one overestimate and 2 underestimates using the time interval
      defined by the lowest and highest 95% confidence limit of both models. These
      results provide further evidence of the usefulness of the predictive models in
      estimating the time of last oral THC ingestion after single or multiple doses.

PMID- 16885723
TI  - Delta(9)-tetrahydrocannabinol, 11-hydroxy-delta(9)-tetrahydrocannabinol and 11
      nor-9-carboxy-delta(9)-tetrahydrocannabinol in human plasma after controlled oral
      administration of cannabinoids.
AB  - A clinical study to investigate the pharmacokinetics and pharmacodynamics of oral
      tetrahydrocannabinol was performed. This randomized, double-blind, placebo
      controlled, within-subject, inpatient study compared the effects of THC
      containing hemp oils in liquid and capsule form to dronabinol (synthetic THC) in
      doses used for appetite stimulation. The National Institute on Drug Abuse
      Institutional Review Board approved the protocol and each participant provided
      informed consent. Detection times and concentrations of THC, 11-hydroxy-Delta
      tetrahydrocannabinol (11-OH-THC), and 11-nor-9-carboxy-Delta-tetrahydrocannabinol
      (THCCOOH) in plasma were determined by gas chromatography-mass spectrometry
      [limits of quantification (LOQ)=0.5, 0.5, and 1.0 ng/mL, respectively] after oral
      THC administration. Six volunteers ingested liquid hemp oil (0.39 and 14.8 mg
      THC/d), hemp oil in capsules (0.47 mg THC/d), dronabinol capsules (7.5 mg THC/d),
      and placebo. Plasma specimens were collected during and after each dosing
      condition. THC and 11-OH-THC concentrations were low and never exceeded 6.1
      ng/mL. Analytes were detectable 1.5 hour after initiating dosing with the 7.5 mg
      THC/d regimen and 4.5 hour after starting the 14.8 mg THC/d sessions. THCCOOH was
      detected 1.5 hour after the first dose, except for the 0.47 mg THC/d session,
      which required 4.5 hour for concentrations to reach the LOQ. THCCOOH
      concentrations peaked at 3.1 ng/mL during dosing with the low-dose hemp oils.
      Plasma THC and 11-OH-THC concentrations were negative for all participants at all
      doses within 15.5 hours after the last THC dose. Plasma THCCOOH persisted for at
      least 39.5 hours after the end of dosing and at much higher concentrations (up to
      43.0 ng/mL). This study demonstrated that subjects who used high THC content hemp
      oil (347 mug/mL) as a dietary supplement had THC and metabolites in plasma in
      quantities comparable to those of patients using dronabinol for appetite
      stimulation. There was a significant correlation between body mass index and Cmax
      and body mass index and number of specimens positive for THC and 11-OH-THC.

PMID- 16885725
TI  - Stereoselective quantification of methadone and a d(6)-labeled isotopomer using
      high performance liquid chromatography-atmospheric pressure chemical ionization
      mass-spectrometry: application to a pharmacokinetic study in a methadone
      maintained subject.
AB  - There is evidence that the apparent oral clearance of rac-methadone is induced
      during the early phase of methadone maintenance treatment. However, it is not
      known if this is due to changes in bioavailability or if this phenomenon is
      stereoselective. This knowledge can be obtained by administering a dose of stable
      labeled methadone at selected times during ongoing treatment. Therefore, the
      authors developed a stereoselective high performance liquid chromatography
      atmospheric pressure chemical ionization mass-spectrometry assay for the
      quantification of the enantiomers of methadone and a d(6)-labeled isotopomer. The
      compounds were quantified in a single assay after liquid-liquid extraction and
      stereoselective high performance liquid chromatograph with atmospheric pressure
      chemical ionization-mass spectrometry detection. The following ions were
      monitored: m/z 310.15 for unlabeled methadone; m/z 316.15 for methadone-d(6); and
      m/z 313.15 for the methadone-d(3) (internal standard). Calibration curves ranged
      from 0.5 to 75 ng/mL for each compound. Extraction recovery was approximately 80%
      for all analytes, without evidence of differences between the unlabeled and
      stable-labeled compounds or concentration dependency. Minor ion promotion was
      observed (<15%) but this was identical for all analytes including the d(3)
      labeled internal standard, with peak area ratios in extracted samples identical
      to control injections. The isotopomers did not alter each others' ionisation,
      even at 10:1 concentration ratios, and 10-fold diluted samples were within 10% of
      the nominal concentration. Assay performance was acceptable, with interassay and
      intra-assay bias and precision <10% for all compounds, including the upper and
      lower limits of quantitation. In conclusion, the assay was successfully applied
      to quantify the concentration of the methadone enantiomers of both orally
      administered unlabeled methadone and an intravenous 5 mg dose of methadone-d(6)
      in a patient receiving chronic oral methadone maintenance therapy.

PMID- 16885724
TI  - The significance of putative urinary markers of illicit heroin use after
      consumption of poppy seed products.
AB  - After consumption of poppy seeds various substances were detected in urine or
      blood samples using an immunoassay and a sophisticated liquid chromatographic
      tandem mass spectrometric procedure. These compounds are widely considered to be
      putative markers of heroin (HER) abuse whereas acetylcodeine was regarded as a
      marker for illicit preparations ("street HER"). Besides positive urinary opiate
      immunoassay results during a 48 hours monitoring period, peak concentrations of
      morphine (MOR), codeine and their glucuronides appeared 4 to 8 hours after
      ingestion of poppy seeds, and concentrations of total MOR higher than 10
      microg/mL were observed. Also, in serum samples taken up to 6 hours after
      consumption, MOR glucuronides were found. Free MOR was only detected in traces (1
      to 3 ng/mL) within 2 hours of consumption. In addition, 3 of 6 onsite opiate
      sweat tests revealed positive results 6.5 hours after ingestion. Furthermore, it
      was demonstrated that neither noscapine (NOS) nor papaverine (PAP) was detectable
      in urine or blood samples after the consumption of poppy seeds containing up to
      94 microg NOS and up to 3.3 mug PAP. NOS and PAP were rapidly metabolized,
      whereas desmethylpapaverine and, especially, its glucuronide were found in urine
      samples of poppy seed consumers even 48 hours after consumption. According to
      these results PAP metabolites should not be regarded as markers of illicit HER
      abuse. In conclusion, only acetylcodeine can be regarded as a specific marker but
      has the problem of a short half-life. Therefore, we suggest that NOS and PAP, but
      not their metabolites, might be used cautiously as additional markers of illicit
      HER abuse as they have not been detected after oral intake of poppy seeds in
      normal doses. But it must be kept in mind that in some cases poppy seeds with an
      unusually high content of these alkaloids could be available, and that these
      substances are also agents in some pharmaceuticals.

PMID- 16885726
TI  - Abuse of nutmeg (Myristica fragrans Houtt.): studies on the metabolism and the
      toxicologic detection of its ingredients elemicin, myristicin, and safrole in rat
      and human urine using gas chromatography/mass spectrometry.
AB  - Seeds of nutmeg are used as spice, but they are also abused because of
      psychotropic effects described after ingestion of large doses. It was postulated
      that these effects could be attributable to metabolic formation of amphetamine
      derivatives from the main nutmeg ingredients elemicin (EL), myristicin (MY), and
      safrole (SA). In a case of a suspected nutmeg abuse, neither such amphetamine
      derivatives nor the main nutmeg ingredients could be detected in urine. The
      metabolites of EL, MY, and SA were identified using gas chromatography-mass
      spectrometry in rat urine and their presence in human urine of the nutmeg abuser
      was confirmed. The identified metabolites indicated that EL, MY, and SA were once
      and twice hydroxylated at the side chain. In addition, EL was O-demethylated at 2
      positions followed by side chain hydroxylation. MY and SA were demethylenated and
      subsequently methylated. In the human urine sample, the following metabolites
      could be identified: O-demethyl elemicin, O-demethyl dihydroxy elemicin,
      demethylenyl myristicin, dihydroxy myristicin, and demethylenyl safrole. As in
      the human urine sample, neither amphetamine derivatives nor the main nutmeg
      ingredients could be detected in the rat urine samples. Finally, toxicologic
      detection of nutmeg abuse was possible by identification of the described
      metabolites of the EL, MY, and SA in urine applying the authors' systematic
      toxicologic analysis procedure using full-scan gas chromatography-mass
      spectrometry after acid hydrolysis, liquid-liquid extraction of analytes, and
      microwave-assisted acetylation of extracted analytes.

PMID- 16885728
TI  - Therapeutic drug monitoring of antithyroid drugs in pregnancy: the knowledge
      gaps.

PMID- 16885729
TI  - Coblation versus unipolar electrocautery tonsillectomy: a prospective,
      randomized, single-blind study in adult patients.
AB  - OBJECTIVES: To determine if the coblation tonsillectomy (subcapsular dissection)
      results in less postoperative pain, equivalent intraoperative blood loss,
      equivalent postoperative hemorrhage rates, and faster healing compared with
      tonsillectomy was performed using unipolar electrocautery in adult patients.
      STUDY DESIGN: The authors conducted a prospective clinical trial. METHODS: Forty
      eight patients underwent tonsillectomy and were randomly assigned to have one
      tonsil removed with coblation and the other with unipolar electrocautery. Outcome
      measures included time to remove each tonsil, intraoperative blood loss, patient
      reported pain, postoperative hemorrhage, and amount of healing 2 weeks after
      surgery. RESULTS: Mean time to remove a single tonsil with coblation and
      electrocautery was 8.22 minutes and 6.33 minutes, respectively (P = .011). Mean
      intraoperative blood loss for each technique was less than 10 mL. Postoperative
      pain was significantly less with coblation as compared with electrocautery: 18.6%
      less painful during the first week of recovery. Seventy percent of blinded
      patients identified the coblation side as less painful during the overall 14-day
      convalescent period. Postoperative hemorrhage rates (2.1% for coblation and 6.2%
      for electrocautery) were not significantly different. No difference in tonsillar
      fossa healing was observed between the two techniques 2 weeks after surgery.
      During nine of the 48 surgeries, wires on the tip of the coblation handpiece
      experienced thinning to the point of discontinuity while removing a single
      tonsil. CONCLUSIONS: Coblation subcapsular tonsillectomy was less painful than
      electrocautery tonsillectomy in this 48-patient group. On average, intraoperative
      blood loss was less than 10 mL for both techniques. Postoperative hemorrhage
      rates and the degree of tonsillar fossa healing were similar between the two
      techniques. The coblation handpiece experienced degradation of vital wires in 18%
      of cases necessitating the use of a second, new handpiece.

PMID- 16885730
TI  - Multichannel cochlear implants: relation of histopathology to performance.
AB  - OBJECTIVES: To determine the relationship of surviving neural elements to
      auditory function in multichannel cochlear implant temporal bones. STUDY DESIGN:
      Case series of all 14 existing multichannel cochlear implants in our temporal
      bone collection. METHODS: Devices included Nucleus 22 (n = 11), Nucleus 24 (n =
      1), Ineraid (n = 1), and Clarion (n = 1). Morphologic evaluation of structural
      elements including spiral ligament, stria vascularis, hair cells, peripheral
      processes, and spiral ganglion cells was performed. Clinical performance data
      were obtained from patient charts. For eight patients, nonimplanted contralateral
      temporal bones were available and paired comparisons were made. RESULTS: Despite
      frequent absence of hair cells and peripheral processes, all bones had at least
      some remaining spiral ganglion cells. Percent of normal remaining structures were
      unrelated to auditory performance with the implant for any of the structural
      elements. Ganglion cell count in segment III showed significant negative
      correlations to speech discrimination scores for words and sentences (Rhos = 
      .687 and -.661, P < or = .03 and .04) as did segment IV and total ganglion cell
      count with word score (Rhos = -.632 and -.638; P < or = .05). Spiral ganglion
      cell survival did not differ between implanted and nonimplanted ears, with the
      exception of segment I, which had fewer cells in the implanted ear (P < or =
      .028). CONCLUSIONS: Performance variability of cochlear implants cannot be
      explained on the basis of cochlear neuronal survival. Although hair cells and
      peripheral processes were frequently absent or greatly diminished from normal,
      all subjects had at least some spiral ganglion cells. And, in this series, there
      was an inverse relationship between survival of ganglion cells and performance.

PMID- 16885731
TI  - Magnetic resonance imaging compatibility and safety of the SOUNDTEC Direct
      System.
AB  - OBJECTIVE/HYPOTHESIS: The purpose of this study was to evaluate magnetic
      resonance imaging (MRI) compatibility and safety of an electromagnetic implanted
      hearing device (the SOUNDTEC Direct System; SOUNDTEC, Inc., Oklahoma City, OK)
      implant during a 0.3-Tesla open MRI imaging examination of the head and neck and
      to develop an MRI protocol that maximizes patient safety while minimizing the
      need for implant removal. The current literature regarding MRI compatibility of
      implantable hearing devices was reviewed. STUDY DESIGN: Linear and torsional
      forces, heating, and implant magnetization were evaluated in vitro. Implanted
      fresh-frozen human temporal bones were used to evaluate image distortion. A
      prospective study of 11 volunteers previously implanted with the SOUNDTEC Direct
      System was conducted to evaluate MRI compatibility and safety. A MEDLINE search
      of the literature between 1980 and July 2005 was reviewed to summarize MRI
      compatibility testing of implantable hearing devices. METHODS: Torsional and
      linear forces experienced by eight implant magnets were measured using calibrated
      neurologic Von Frey Hairs and compared with finite element analysis predictions
      as well as forces required to separate the incudostapedial joints of 12 fresh
      frozen human temporal bones. Implant heating was determined by measuring the
      temperature change of eight implant vials compared with saline controls
      immediately after a head MRI scan. Implant magnetization was evaluated after
      repeated exposure to a 0.3-Tesla magnetic field. An 11-patient prospective study
      was performed to evaluate MRI compatibility in a 0.3-Tesla open MRI environment
      using adult volunteers previously implanted with the SOUNDTEC Direct System. A
      modified MRI protocol was developed to maximize patient safety. Each individual
      underwent an audiometric and otologic examination immediately before and after
      MRI. RESULTS: Peak linear force at the MRI entry measured 0.5 g +/- 0.2 standard
      deviation (SD). Maximum torque occurred at isocenter and measured 11.4 g-cm +/-
      1.2 SD. The mean torque required to separate the incudostapedial joint was 33.8 g
      cm +/- 20.4 SD. The average increase in temperature of the eight implant vials
      was 0.45 degrees C +/- 0.11 SD, whereas the increase in temperature of the three
      saline controls measured 0.47 degrees C +/- 0.11 SD. The average change in
      magnetic flux density of the 14 implant magnets tested was 22.0 gauss. Maximum
      image distortion occurred during the gradient echo sequence and measured 8.6 cm
      in diameter with a volume of 5,096 mm. Eleven patients completed a total of 12
      head, one shoulder, and three lumbar 0.3-Tesla open MRI scans without patient- or
      device-related complications other than degradation of the MR image. There was no
      report of discomfort, tinnitus, dizziness, change in hearing, or change in device
      performance. All post-MRI changes in pure-tone thresholds, speech discrimination,
      soundfield thresholds, and aided soundfield thresholds were within the range of
      test-retest variability. CONCLUSION: When considering MRI of implantable
      ferromagnetic hearing devices, issues related to mechanical forces, implant
      heating, current induction, implant demagnetization, image degradation, and
      acoustic trauma must be considered. The SOUNDTEC Direct System is both MRI
      compatible and safe in a 0.3-Tesla open MRI environment when a modified protocol
      is used. Degradation of the head MRI image may impair visualization of the
      ipsilateral temporal bone and adjacent structures within a 2.5- to 4.3-cm radius
      of the implant and is minimized by using a fast spin echo sequence.

PMID- 16885732
TI  - Electrical resistivity measurements in the mammalian cochlea after neural
      degeneration.
AB  - OBJECTIVES/HYPOTHESIS: In the present series of experiments, the effect of neural
      degeneration on the cochlear structure electrical resistivities was evaluated to
      test if it alters the current flow in the cochlea and if increased current levels
      are needed to stimulate the impaired cochlea. In cochlear implants, frequency
      information is encoded in part by stimulating discrete populations of spiral
      ganglion cells along the cochlea. However, electrical properties of the cochlear
      structures result in shunting of the current away from the auditory neurons. This
      consumes energy, makes cochlear implants less efficient, and drastically reduces
      battery life. Models of the electrically stimulated cochlea serve to make
      predictions on current paths using modified and improved cochlear implant
      electrodes. However, one of the model's shortcomings is that most of the values
      for tissue impedances are not direct measurements. They are derived from bulk
      impedance measurements, which are fitted to lumped-element models. STUDY DESIGN:
      The four-electrode reflection-coefficient technique was used to measure
      resistivities in the gerbil cochlea. In vivo and in vitro (the hemicochlea)
      models were used. Measurements were made in normal and in deafened animals.
      Cochlear damage was induced by neomycin injection into the animals' middle ears.
      Neural degeneration was allowed to occur over 2 months before performing the
      measurements in the deafened animals. RESULTS: The resistivity values in deafened
      animals were smaller than in the normal-hearing animals, thus altering the
      current flow within the cochlea. CONCLUSIONS: Resistivity changes and subsequent
      changes in current path should be considered in future designs of cochlear
      implants.

PMID- 16885733
TI  - Fungal speciation using quantitative polymerase chain reaction (QPCR) in patients
      with and without chronic rhinosinusitis.
AB  - OBJECTIVES/HYPOTHESIS: The objectives of this study were to determine the
      mycology of the middle meatus using an endoscopically guided brush sampling
      technique and polymerase chain reaction laboratory processing of nasal mucous; to
      compare the mycology of the middle meatus in patients with sinus disease with
      subjects without sinus disease; to compare the responses on two standardized
      quality-of-life survey forms between patients with and without sinusitis; and to
      determine whether the presence of fungi in the middle meatus correlates with
      responses on these data sets. STUDY DESIGN: The authors conducted a single-blind,
      prospective, cross-sectional study. METHODS: Patients with sinus disease and a
      control group without sinus disease were enrolled in the study. A disease
      specific, validated Sinonasal Outcomes Test survey (SNOT-20) was completed by the
      subjects and a generalized validated Medical Outcomes Short Form 36 Survey (SF
      36) was also completed. An endoscopically guided brush sampling of nasal mucous
      was obtained from the middle meatus. Fungal specific quantitative polymerase
      chain reaction (QPCR) was performed on the obtained sample to identify one of 82
      different species of fungus in the laboratory. Statistical analysis was used to
      categorize the recovered fungal DNA and to crossreference this information with
      the outcomes surveys. RESULTS: The fungal recovery rate in the study was 45.9% in
      patients with sinus disease and 45.9% in control subjects. Patients with chronic
      rhinosinusitis had a mean SNOT-20 score of 1.80 versus the control group mean
      score of 0.77 (P < .0001). SF-36 data similarly showed a statistically
      significant difference between diseased and control populations with controls
      scoring a mean of 80.37 and patients with chronic rhinosinusitis scoring a mean
      of 69.35 for a P value of .02. However, no statistical significance could be
      ascribed to the presence or absence of fungi recovered, the type of fungi
      recovered, or the possible impact of fungi on the quality-of-life survey results.
      CONCLUSION: The recovery rate of fungi from the middle meatus of patients with
      chronic rhinosinusitis and a control population without chronic rhinosinusitis is
      45.9% using QPCR techniques. No direct causation with regard to fungal species or
      presence was proven; however, a species grouping for future studies is proposed
      based on trends in this data and other reports. Disease-specific outcomes surveys
      revealed a statistically significant difference between the two groups.

PMID- 16885734
TI  - Petrous apex effusion: a clinical disorder.
AB  - INTRODUCTION: Petrous apex fluid accumulations without evidence of acute
      infection are routinely managed as "leave alone lesions" without potential
      morbidity. Are petrous apex fluid accumulations (effusions) in the absence of
      acute infection always asymptomatic without the need for treatment? If petrous
      apex effusions can produce symptoms separate from acute infections, what are the
      clinical outcomes in these patients? STUDY DESIGN: Retrospective clinical review.
      METHODS: A retrospective record review of 31 patients presenting with petrous
      apex effusions was performed with recording of clinical characteristics,
      interventions, and outcomes. RESULTS: Eighteen of the 31 patients had clinical
      symptoms referable to the petrous apex effusion with the following
      characteristics: indolent and previous infections (4), hearing loss (3), headache
      and pressure alone (8), facial spasms (1), and positional vertigo (2). Overall, 5
      of 18 symptomatic patients resolved with antibiotics, steroids, or positioning
      maneuvers. Three of five infracochlear drainages produced symptom resolution.
      Three of four patients undergoing retrolabyrinthine drainage had symptom
      resolution, and four of seven middle fossa drainages yielded symptom resolution.
      In contrast, infratemporal fossa drainage procedures did not resolve the
      patients' symptoms. CONCLUSIONS: Isolated petrous apex effusions are rare, but
      they can cause symptoms. If medical management fails, surgical drainage based on
      the location is appropriate. The surgical drainage approach selected
      (infracochlear, infralabyrinthine, middle fossa, and endoscopic transnasal)
      should be based on an anatomic consideration of the involved petrous apex air
      cells (superior vs. inferior) and the relative position of the carotid artery and
      jugular bulb.

PMID- 16885735
TI  - Management of frontal sinus fractures: a review of 96 cases.
AB  - OBJECTIVES: The optimal treatment algorithm for frontal sinus fracture management
      remains ill-defined. The purpose of the study was to classify fracture types,
      review management methods, document associated injuries, and identify
      complications associated with various treatment options. STUDY DESIGN: The
      authors conducted a retrospective chart review evaluating a 13-year experience
      with frontal sinus fracture management. METHODS: Complete medical records of 96
      frontal sinus fracture patients treated by the University of Kentucky
      Otolaryngology Service from 1990 to 2003 were reviewed. RESULTS: The average
      patient age was 39 years. Fifty percent of the fractures involved the anterior
      table of the frontal sinus alone, and 50% involved both anterior and posterior
      tables. Forty-seven percent of the injuries were managed with observation,
      whereas 50% of patients underwent surgical repair. In the surgical group, 60%
      underwent open reduction and internal fixation (ORIF), 23% had a cranialization
      procedure, and 17% underwent sinus obliteration. The average length of follow up
      was 9 months. Complications occurred in 17% of the patients (5% in the
      nonsurgical group and 12% in the surgical group). CONCLUSION: Our results support
      conservative management of nondisplaced or minimally displaced fractures based on
      the low complication rate seen in this series. Significant bone displacement can
      frequently be managed with simple ORIF. Complex fractures affecting the orbit or
      intracranial contents require cranialization or possibly obliteration. A subset
      of patients with suspected frontal sinus outflow obstruction can be considered
      for observation or simple ORIF with close follow up and endoscopic repair if
      outflow complications manifest.

PMID- 16885736
TI  - In vivo and in vitro characterization of bone marrow-derived stem cells in the
      cochlea.
AB  - OBJECTIVES/HYPOTHESIS: Stem cell replacement therapy has the potential to treat
      or cure an array of degenerative neurologic disorders, including sensorineural
      deafness. However, little is known about the potential for marrow-derived stem
      cells (MSCs) to take on properties of spiral ganglion neurons. The main purpose
      of this prospective animal study was to evaluate the survival of MSCs
      transplanted into the gerbil cochlea. METHODS: Eight 3- to 4-month-old Mongolian
      gerbils were used as recipients. The animals received an intraperilymphatic
      transplantation of 100,000 green fluorescent protein (GFP)-positive MSCs with
      scala tympani injection and modiolar injection. Seven days after transplantation,
      MSC survival was evaluated by microscopic examination of frozen sections cut
      through the cochleae of the recipient animals. RESULTS: MSCs isolated from the
      TgN (ACTbEGFP) mouse line used in this study exhibited bright green florescence
      after five to seven passages in vitro. Seven days after postoperatively, most
      transplanted MSCs were found in the scala tympani and scala vestibule and only a
      small number located in the scala media in animals that received both forms of
      injection. There were no GFP-positive MSCs in the modiolus in animals with scala
      tympani injection. In contrast, the mean profile count in animals with modiolar
      injection was 28, which was the highest in all regions. Although MSCs have the
      potential to migrate, the anatomic barrier between the perilymphatic space and
      the modiolus might account for the absence of GFP-positive MSCs in this region.
      CONCLUSION: These findings may have important clinical implications as a means of
      delivering MSCs in the cochlea for cell replacement therapy.

PMID- 16885737
TI  - Orbital sequelae of rhinosinusitis after cochlear implantation in children.
AB  - OBJECTIVES: The objectives of this retrospective case review were to describe
      orbital complications in children after cochlear implantation, to define
      rhinosinusitis as a possible preoperative risk factor, and to suggest a possible
      pathophysiological mechanism for this previously unreported occurrence. METHODS:
      Records of children undergoing cochlear implantation over a 7-year period at a
      tertiary academic medical center were reviewed. Four children who experienced
      postoperative orbital sequelae were identified. We describe the demographics,
      clinical course, and radiologic findings in these children. RESULTS: The records
      of 91 children who underwent cochlear implantation were reviewed. The mean age
      was 6.0 years (range, 0.9-16.9 years). Forty-nine children (54%) were female and
      51 (56%) were white. Four children developed postoperative orbital complications
      on the ipsilateral side to implantation. Orbital complications were characterized
      by periorbital edema and preseptal cellulitis necessitating prolonged
      hospitalization in all four children (mean length of stay, 3.3 days). Each
      child's orbital complication resolved with medical therapy that included
      intravenous antibiotics and nasal saline. Temporal bone images before
      implantation showed evidence of rhinosinusitis in all four cases. Of 76 available
      preoperative scans from the unaffected children, only 11 (14%) studies showed
      evidence of rhinosinusitis. CONCLUSIONS: Children with preoperative radiologic
      evidence of rhinosinusitis may be at risk of orbital sequelae after cochlear
      implantation. Positioning of the patient during surgery, length of surgery, and
      minor trauma to the lamina papyracea during drilling of the mastoid may be
      important etiologic factors. A careful review of medical history and computed
      tomography imaging before implantation may identify at-risk children.

PMID- 16885738
TI  - Presence of human papillomavirus DNA in tonsillectomy specimens.
AB  - OBJECTIVES: The objectives of this prospective case-control study were to study
      the prevalence of human papillomavirus (HPV) in tonsillectomy specimens from
      pediatric patients without recurrent respiratory papillomatosis (RRP), and to
      study methods of HPV detection. METHODS: Fifty pediatric patients without known
      RRP undergoing tonsillectomy for hypertrophy or recurrent tonsillitis were
      enrolled in the study. After tonsillectomy, a 20-mg section was subjected to DNA
      extraction, and DNA content and purity were confirmed with spectrophotometry.
      Polymerase chain reaction (PCR) was performed using consensus primer pools PGMY
      09/11 targeted at the L1 region. Amplification products were detected and
      analyzed with standard agarose gel electrophoresis. Positive samples were then
      subjected to reverse line blot assay to determine virus genotype. Laryngeal
      papilloma specimens of 15 patients obtained during routine debulking procedures
      were also analyzed and served as positive controls. RESULTS: Of 50 tonsil samples
      tested, two were positive for HPV DNA after PCR and gel electrophoresis. One of
      these samples was confirmed with typing and tested positive for HPV 11. All 15
      papilloma specimens were positive for DNA of HPV types 6 and/or 11. CONCLUSIONS:
      In the current study, the prevalence of HPV DNA in tonsillar tissue of patients
      without RRP is 2%, whereas the incidence of this disease is 2 to 4 cases per
      100,000 (0.004%). These findings are significantly different (P = .005 within a
      95% confidence interval) suggesting that host factors in addition to infection
      play a role in pathogenesis of RRP. The molecular methods described in this study
      are well suited for detection of HPV in tonsillar tissue.

PMID- 16885739
TI  - Pilot study of mucosal genetic differences in early smokers and nonsmokers.
AB  - BACKGROUND: Global gene expression analysis is proving to be an important means
      of assessing human tumors and may identify key components of carcinogenesis or
      clinical prognosis. This technique has been successfully applied to head and neck
      squamous cell carcinoma (HNSCC) and thyroid carcinomas; however, little has been
      done to evaluate premalignant states. METHODS: Human buccal mucosal cells were
      sampled from smokers and nonsmokers using a noninvasive brush technique. The
      method was validated by assessing the quantity and quality of RNA obtained. The
      purified RNA was then assayed using cDNA microarrays containing 27,323 cDNA
      clones to examine the buccal mucosa in these patients for differences in gene
      expression patterns. Using unsupervised and supervised hierarchical clustering
      methods, we developed a gene profile signature for an initial training set of
      smokers and nonsmokers and then used this to predict smoking status in a
      subsequent test set of subjects. Selected genes were then cross-referenced with
      previously published gene sets found in HNSCC identified by our group. RESULTS:
      Nineteen subjects were used in this pilot analysis, 9 smokers and 10 nonsmokers.
      Smoking among the study group ranged from 1 to 60 pack years. RNA purified from
      buccal mucosal brushing demonstrated a high degree of similarity in gene
      expression profiles among independent samples. Through the application of
      supervised clustering techniques, we were able to identify 113 genes whose
      expression differed significantly between samples from smokers and nonsmokers (t
      test, P < .001). This expression signature was able to accurately predict who
      within the second set of subjects were smokers, with the exception of one person
      who had a minimal tobacco history and clustered with the nonsmokers. Cross
      referencing data with that found in HNSCC, we were able to identify a tumor
      suppressor gene involved in the c-myc pathway (Mxi1) that was similarly under
      expressed in smokers and cancer patients with progressive disease. CONCLUSIONS:
      Although the sample size was small in this preliminary dataset, our analysis
      revealed several groups of genes that were either over- or under-expressed in the
      smokers and which could be used to predict smoking exposure. Many of these
      represent genes of possible interest as early molecular markers for head and neck
      carcinogenesis.

PMID- 16885740
TI  - Parathyroid adenoma localization: surgeon-performed ultrasound versus sestamibi.
AB  - OBJECTIVES: Compare surgeon-performed ultrasound versus sestamibi for
      preoperative parathyroid adenoma localization. STUDY DESIGN: Single-institutional
      cohort. METHODS: One hundred six consecutive patients undergoing
      parathyroidectomy at an academic institution between 2004 to 2005 were included.
      Of those, 103 underwent both surgeon-performed ultrasound and sestamibi-Tc99m
      localization preoperatively. Primary outcome is sensitivity for adenoma
      localization to correct quadrant (right vs. left, superior vs. inferior).
      RESULTS: Hypercalcemia resolved in 97% of patients. Sensitivities for correct
      quadrant localization for ultrasound versus sestamibi were 87% versus 58% (P <
      .001). Specificities were 95%. Positive and negative predictive values were 85%
      versus 78% and 96% versus 87%, respectively. Combined sensitivity was 93%.
      Sensitivities for correct side localization were 91% and 74% (P = .002).
      CONCLUSIONS: Ultrasound appears more sensitive than sestamibi for localization to
      correct quadrant or side when performed in-office by the author in this cohort.

PMID- 16885741
TI  - Multimodality approach to management of the paralyzed face.
AB  - OBJECTIVES: Despite the ability of facial reanimation techniques to introduce
      meaningful movement to the paralyzed face, dynamic methods do not address all
      zones of the face. Our objective was to retrospectively review outcomes after
      multimodality management of the patient with facial paralysis, to describe
      several novel surgical methods that introduce subtle improvements in static
      facial balance, and to present an algorithm for comprehensive management of the
      paralyzed face. METHODS/RESULTS: Three hundred thirty-seven patients with facial
      paralysis were seen and treated in a busy facial nerve center setting over a 3
      year period using a range of standard muscle transfers, physical therapy,
      chemodenervation with botulinum toxin, and static surgical techniques. Three
      adjunct techniques emerged as novel and useful procedures that more fully
      addressed facial balance issues than existing techniques. Of patients proceeding
      with physical therapy, greater than 80% of patients experienced a benefit, and
      97% of those who proceeded with botulinum toxin therapy experienced a benefit.
      CONCLUSIONS: Facial paralysis is best managed using a multimodality approach that
      includes surgical interventions, physical therapy, and chemodeneveration. We
      describe three adjunctive surgical techniques for management of the paralyzed
      face and present a comprehensive algorithm for management of the paralyzed face.
      That may provide improved function and cosmesis in all zones of the paralyzed
      face.

PMID- 16885742
TI  - Gleevec suppresses p63 expression in head and neck squamous cell carcinoma
      despite p63 activation by DNA-damaging agents.
AB  - OBJECTIVES: The objectives of this study were to determine the effects of Gleevec
      on p63 expression in head and neck squamous cell carcinoma (HNSCC) cell lines and
      to investigate the role of Gleevec in regulating p63 stabilization under DNA
      damaging conditions. METHODS: Immunohistochemical staining was performed to
      determine p63 expression in HNSCC tissue. Annexin V staining was used to assess
      the effects of p63 on early apoptosis. Immunoblotting was used to examine the
      effects of Gleevec on p63 protein levels in HNSCC cell lines in response to DNA
      damage. Immunofluorescence staining was performed to study the expression pattern
      of p63 and c-Abl. RESULTS: In HNSCC, p63 protein levels are induced by DNA
      damaging agents, including ionizing radiation, doxorubicin, and ultraviolet
      light. We demonstrate that Gleevec reduces p63/DeltaNp63 expression in a dose
      dependent manner in HNSCC and overrides the protein induction by DNA-damaging
      agents. Overexpression of c-Abl in the absence of Gleevec results in higher
      levels of p63 than those treated with Gleevec, implicating c-Abl kinase activity
      as a regulator of p63 protein stability. CONCLUSIONS: Gleevec downregulates
      p63/DeltaNp63 levels in HNSCC in a dose-dependent manner under both normal and
      DNA-damaging conditions. This downregulation can be explained by Gleevec's
      inhibition of c-Abl, which destabilizes p63. Based on our data, treating cancers
      with high expression of TAp63 with Gleevec may result in the unfavorable
      inhibition of a tumor suppressor, whereas downregulation of DeltaNp63 would be
      advantageous. Further development of antibodies that can discriminate between
      TAp63 and DeltaNp63 will be needed to determine the specific effects of Gleevec
      on p63 in HNSCC.

PMID- 16885743
TI  - Improved infant swallowing after gastroesophageal reflux disease treatment: a
      function of improved laryngeal sensation?
AB  - OBJECTIVE: The objective of this study was to describe improvements in pediatric
      swallowing after gastroesophageal reflux treatment. STUDY DESIGN: The authors
      conducted a retrospective database and chart review at two tertiary care
      children's hospitals. PARTICIPANTS: Patients (21 males, 7 females) ranged in age
      from 1 to 32 months. All patients had clinical evidence of gastroesophageal
      reflux disease (GERD) as well as evidence of dysphagia with aspiration (laryngeal
      vestibule and/or trachea) or hypopharyngeal pooling on flexible endoscopic
      evaluation of swallowing and sensation testing (FEESST) or videofluoroscopic
      swallow study (VSS). INTERVENTION: Each child underwent either medical or
      surgical intervention for control of their GERD. OUTCOME MEASURES: Outcome
      measures were change in laryngopharyngeal sensation and swallowing function with
      repeat swallow evaluation after GERD treatment. RESULTS: A significant
      improvement in both swallow function and sensory testing was demonstrated after
      GERD treatment. CONCLUSIONS: GERD may result in decreased laryngopharyngeal
      sensitivity, which may contribute to pediatric swallowing dysfunction. Control of
      GERD may improve swallow function. These findings have important clinical
      implications that need further study.

PMID- 16885744
TI  - Cochleosaccular dysplasia associated with a connexin 26 mutation in keratitis
      ichthyosis-deafness syndrome.
AB  - OBJECTIVE: The objective of this study was to characterize the temporal bone
      phenotype associated with a mutation of GJB2 (encoding connexin 26). STUDY
      DESIGN: The authors conducted correlative clinical, molecular genetic, and
      postmortem histopathologic analysis. METHODS: The study subject was a male infant
      with keratitis-ichthyosis-deafness (KID) syndrome. We performed a nucleotide
      sequence analysis of GJB2 and a histopathologic analysis of the temporal bones.
      RESULTS: The subject was heterozygous for G45E, a previously reported KID
      syndrome mutation of GJB2. The primary inner ear abnormality was dysplasia of the
      cochlear and saccular neuroepithelium. CONCLUSIONS: GJB2 mutations can cause
      deafness in KID syndrome, and possibly in other GJB2 mutant phenotypes, by
      disrupting cochlear differentiation.

PMID- 16885746
TI  - Early endoscopic treatment of acute inflammatory airway lesions improves the
      outcome of postintubation airway stenosis.
AB  - OBJECTIVES/HYPOTHESIS: The objective of this study was to compare the results of
      treating acute postintubation stenotic airway lesions with the results of
      treating mature lesions and to assess whether early intervention improves the
      outcome. METHODS: Patients without previous surgery, treated for postintubation
      airway stenosis, were reviewed. Those with airway lesions presenting within weeks
      of intubation (n = 11) were treated with intralesional steroids, laser reduction,
      and balloon dilatation. Patients with mature airway lesions (n = 20) were
      initially treated with laser, balloon dilatation, and topical mitomycin C.
      Preoperative patient and lesion characteristics, details of the treatment, and
      intervention-free intervals were recorded. Data were compared with unpaired
      Student t test or chi test as appropriate, and intervention-free intervals were
      compared with log-rank statistics. Cox regression was used to identify
      independent predictors of intervention-free interval. RESULTS: There were 18
      males and 13 females. The average age at presentation was 47 +/- 2.7 years. The
      two groups were statistically comparable for demographic and lesion
      characteristics. Patients treated for acute injury required significantly fewer
      interventions (P < .03), the majority being treated with a single treatment. They
      had a significantly longer intervention-free interval (P < .02; log-rank
      analysis) and did not require external laryngotracheal reconstruction (P < .001)
      compared with patients treated for mature fibrotic scars leading to airway
      stenosis. CONCLUSIONS: Early treatment of acute fibroinflammatory airway lesions
      has the potential to favorably modify the natural history of postintubation
      tracheal injury, raising the tantalizing possibility of an early cure. These
      findings have significant implications for early identification, referral, and
      treatment of postintubation tracheal stenosis and need to be confirmed with
      further studies.

PMID- 16885745
TI  - STI-571 (Gleevec) potentiates the effect of cisplatin in inhibiting the
      proliferation of head and neck squamous cell carcinoma in vitro.
AB  - OBJECTIVE: The objective of this study was to determine whether STI-571 (Gleevec;
      imatinib mesylate) could sensitize established head and neck squamous cell
      carcinoma (HNSCC) cell lines to the effects of cisplatin. METHODS: Western blot
      analysis and immunofluorescence were used to examine the expression of the
      tyrosine kinases that are known targets of Gleevec, including c-kit, c-Abl, and
      platelet-derived growth factor receptor, on the cell lines, and
      immunohistochemistry was performed to determine the expression of these kinases
      in human HNSCC tissue. Once these targets were confirmed, clonogenic cell
      survival assays were performed to determine the effect STI-571 had on growth and
      proliferation when used in combination with cisplatin compared with STI-571 alone
      or cisplatin alone. Cells were incubated with a range of doses of STI-571 24
      hours before the addition of cisplatin. Flow cytometry analysis was performed to
      determine cell-cycle distribution and to measure apoptosis caused by the various
      treatments. An annexin V assay was also used to further measure apoptosis.
      RESULTS: Our results indicate that STI-571 potentiates the effect of cisplatin
      and leads to a significant decrease in cell proliferation and colony formation
      compared with cisplatin alone in a dose-dependent fashion. Surprisingly, there
      was a slight decrease in the level of apoptosis when Gleevec was used in
      combination with cisplatin compared with cisplatin alone. Gleevec alone resulted
      in a slight increase in G1 phase of the cell cycle, whereas cisplatin alone
      resulted in a G2 arrest. The addition of Gleevec to cisplatin resulted in an
      enhanced S/G2 phase accumulation. Although we did not demonstrate an increase in
      cisplatin-induced cell death, we postulate that the increased S/G2 arrest
      resulting from the DNA damage in the presence of Gleevec results in decreased
      proliferation of HNSCC, resulting in a net decrease in colony formation.
      CONCLUSIONS: The small molecule inhibitor Gleevec, which targets specific
      tyrosine kinases that are expressed in HNSCC, can significantly potentiate the
      antiproliferative effects of cisplatin. Because Gleevec alone has minimal side
      effects, treatment with the combination treatment of cisplatin and Gleevec may
      result in increased efficacy of cisplatin in treating this cancer. Additional
      studies are warranted, keeping in mind that drug combinations may result in
      unexpected toxicities that are not frequently seen with either drug alone.

PMID- 16885747
TI  - Ingestion of caustic substances: a 15-year experience.
AB  - OBJECTIVE: The objective of this study was to analyze the circumstance,
      demographic features, clinical findings, and complications of caustic ingestion
      in relation to the type and amount of caustic substance. STUDY DESIGN: The
      authors conducted a retrospective cohort study in a tertiary medical center.
      METHODS: The authors reviewed medical records from 1988 to 2003 of patients with
      a history of caustic ingestion and clinical signs of injury to the aerodigestive
      tract. Parameters examined included age at presentation, gender, demographic
      status, nature of the caustic substance ingested, amount of substance,
      circumstance of the event, diagnostic tools, degree of injury, and anatomic
      distribution of the injury, early and late complications, and requirement for
      ventilatory support. RESULTS: A total of 50 cases of caustic ingestion were
      identified (age range, 5 months-71 years). A biphasic distribution of the
      patients was noted; half were children under 5 years old and the remainder was
      adults. The most common caustic agent ingested was alkaline (42%) followed by
      acidic (32%) and chlorine bleach (26%). The most frequent cause for ingestion was
      accidental (67%) as opposed to attempt suicide (33%). All cases of attempted
      suicide occurred in adults. Most of them reported ingestion of large amounts of
      caustic substance. In the pediatric group, an association between the caustic
      agent and ethnicity was observed. Among Jewish children, alkaline cleaning agents
      were the most common cause (82%). Acetic acid was the most common substance
      ingested by the Arab children (100%). The findings of rigid esophagoscopy in 36
      patients were as follows: first-degree esophageal injury in 16 (44%), second
      degree in 6 (17%), third-degree in 7 (19%), fourth-degree in 6 (17%), and one
      (3%) was normal. Mucosal injury to the esophagus was worse in the acidic
      ingestion group as compared with the alkaline substance ingestion group with
      marginally statistically significant difference in the median degree of injury
      between the three types of ingested substances (P = .054). Mucosal injury to the
      esophagus was worse among patients who attempted suicide as compared with
      accidental ingestion with a statistically significant difference in the median
      degree of injury between the two reasons for ingestion (P = .002). CONCLUSION:
      Severity of injury from caustic ingestion damages depend on the type of ingested
      substance, which varies depending on ethnicity. Ingestion of caustic agents by
      children involves specific substances according to the season, cultural and
      religious festivals, and ethnicity. The majority of adult cases are intentional
      with more serious injuries and a higher rate of complications. In our series,
      ingestion of acidic substances and ingestion associated with suicide attempt had
      the most severe consequences.

PMID- 16885748
TI  - Detection of osteoprotegerin and TNF-alpha mRNA in ankylotic Stapes footplates in
      connection with measles virus positivity.
AB  - HYPOTHESIS: Otosclerosis is a bone remodeling disorder of the otic capsule
      causing conductive and sensorineural hearing loss. Persistent measles virus
      infection of the temporal bone with increased tumor necrosis factor (TNF)-alpha
      and decreased osteoprotegerin mRNA expression is supposed to be the main
      etiologic factor in otosclerosis. BACKGROUND: Determinants of measles virus
      infection and reactive inflammation were studied in otosclerosis. The presence of
      measles virus was shown in otosclerotic patients by reverse transcriptase
      polymerase chain reaction (RT-PCR) amplification of the viral RNA. No report is
      available, however, about the role and interactions of bone-specific cytokines in
      otosclerosis. METHODS: : Nucleic acid was extracted from stapes footplates of
      clinically otosclerotic patients. Measles virus nucleoprotein RNA was amplified
      by seminested RT-PCR. TNF-alpha and osteoprotegerin mRNA coexpression was
      detected by RT-PCR in otosclerotic bone and was correlated to measles virus
      positivity. RESULTS: Among 154 clinically stapes fixation otosclerotic patients,
      99 stapedes contained measles virus RNA. TNF-alpha mRNA was detectable in 88
      virus-positive and in 6 virus-negative stapes footplates. Osteoprotegerin mRNA
      expression was significantly lower in the TNF-alpha-positive specimens (P <
      .0001) that was independent from virus positivity. CONCLUSION: Detection of TNF
      alpha mRNA demonstrates activated osteoclast functions and inflammatory pathways
      in otosclerotic stapes footplates associated with measles virus presence.
      Increased expression of TNF-alpha and its action on RANK production inhibits the
      protective functions of osteoprotegerin on normal bone turnover in the otic
      capsule.

PMID- 16885749
TI  - Mcm-2 and Ki-67 have limited potential in preoperative diagnosis of thyroid
      malignancy.
AB  - OBJECTIVES: Minichromosome maintenance protein 2 (Mcm-2) is essential for DNA
      replication and serves as a useful biomarker of cell-cycle state in human tissue
      samples. Ki-67 is an established proliferation marker. Because Mcm-2 expression
      has not previously been assessed in thyroid tissue, the aim of this study was to
      assess the expression of both proteins in a range of thyroid lesions to determine
      their potential value as preoperative markers of thyroid malignancy. METHODS: Mcm
      2 and Ki-67 protein expression were assessed by immunohistochemistry in formalin
      fixed, paraffin-embedded thyroid tissues from 128 patients with histologic
      diagnoses of papillary carcinoma (n = 38), follicular carcinoma (n = 22),
      follicular adenoma (n = 33), and dominant nodules of multinodular goitre (n =
      35). RESULTS: Mcm-2 and Ki-67-labeling indices (LIs) were both higher in
      follicular and papillary carcinomas than in follicular adenomas or dominant
      nodules. The Ki-67 LI discriminated better between follicular carcinomas and
      follicular adenomas (P < .0001) than Mcm-2 (P = .0273). However, the Mcm-2 and Ki
      67 LIs overlapped widely between the four histologic groups, and the expression
      of these proteins was also noted to be heterogenous within these lesions.
      CONCLUSION: Neither Mcm-2 or Ki-67 can currently be reliably applied as
      preoperative markers to distinguish benign from malignant thyroid lesions.

PMID- 16885751
TI  - Sphenopalatine endoscopic ganglion block: a revision of a traditional technique
      for cluster headache.
AB  - The diagnosis of chronic cluster headache (CH), the most painful form of
      headache, is based on typical clinical features characterized by strictly
      unilateral pain with no side shift and ipsilateral oculofacial autonomic
      phenomena. The attacks occur several times a day for periods of 1 to 2 months in
      the episodic form of the disease or less frequently on a daily basis in the
      chronic form. The pathogenesis of CH involves the activation of parasympathetic
      nerve structures located within the sphenopalatine ganglion (SPG), which explains
      many of the associated symptoms, whereas the activation of the ipsilateral
      hypothalamic gray matter may explain its typical circadian and circannual
      periodicity. A number of surgical approaches have been tried in cases of chronic
      CH resistant to pharmacologic therapy, of which SPG blockade has been shown to
      have certain efficacy. We have adopted a new technique based on endoscopic
      ganglion blockade that approaches the pterigo-palatine fossa by way of the
      lateral nasal wall and consists of the injection of a mixture of local
      anesthetics and corticosteroids, which was performed in 20 selected patients with
      chronic CH, according to the International Headache Society criteria (18 male, 2
      female; mean age 40 yr), who were selected for SPG blockade because they were
      totally drug resistant. The symptoms improved significantly, but always only
      temporarily, in 11 cases. These results should be considered rather good because,
      unlike other frequently used techniques, SPG blockade is not invasive and should
      therefore always be attempted before submitting patients to more invasive
      surgical approaches.

PMID- 16885752
TI  - Three-dimensional fluid-attenuated inversion recovery magnetic resonance imaging
      findings in patients with sudden sensorineural hearing loss.
AB  - OBJECTIVE: To evaluate the inner ear in sudden sensorineural hearing loss (SNHL)
      using three-dimensional fluid-attenuated inversion recovery (3D-FLAIR) magnetic
      resonance imaging (MRI) at 3 Tesla (T). BACKGROUND: 3D-FLAIR MRI has recently
      been developed to detect high concentrations of protein or hemorrhage.
      Application of this method to sudden SNHL has not been described. METHODS: We
      used 3D-FLAIR at 3 T with and without gadolinium enhancement to evaluate eight
      patients with sudden SNHL. RESULTS: In four of eight ears with idiopathic sudden
      SNHL, high precontrast signals were observed within the inner ear on 3D-FLAIR.
      The high-signal areas observed on 3D-FLAIR were not detected by T1- or T2
      weighted MRI in any of these patients. In one of these four ears, significant
      gadolinium enhancement was observed on 3D-FLAIR. CONCLUSION: Half the patients
      with sudden SNHL examined had high signals in the SNHL-affected ear on 3D-FLAIR
      at 3 T. High precontrast signals in the inner-ear fluid space may reflect minor
      hemorrhage, or an increased concentration of protein that had passed through
      blood vessels with increased permeability, or had originated from disrupted cells
      in the inner ear. Gadolinium enhancement in one ear suggested the breakdown of
      the blood-labyrinth barrier. 3D-FLAIR MRI should contribute markedly to the
      elucidation of pathologic conditions in the inner ears of patients with
      idiopathic sudden SNHL.

PMID- 16885750
TI  - Two temporal bone computed tomography measurements increase recognition of
      malformations and predict sensorineural hearing loss.
AB  - OBJECTIVES/HYPOTHESIS: The objectives of this prospective study were to assess
      the reproducibility of the measurements of the cochlea and lateral semicircular
      canal (LSCC) and to determine if abnormal measurements predict sensorineural
      hearing loss (SNHL). METHODS: Two readers independently measured the cochlear
      height on coronal section and the LSCC bony island width on axial section on 109
      temporal bone computed tomography scans; audiologic data on these patients were
      collected independently from medical records. Inter- and intrareader variability
      was evaluated using intraclass correlation coefficients (ICCs) based on a random
      effects model. The positive and negative predictive values of abnormal
      measurement for hearing loss were determined. RESULTS: There was excellent inter-
      and intraobserver agreement for both measurements (ICC >80%). The average
      cochlear height was 5.1 mm (normal range, 4.4-5.9 mm) and average LSCC bony
      island width was 3.7 mm (normal range, 2.6-4.8 mm). Review of the original
      radiology reports demonstrated that both cochlear hypoplasia and LSSC dysplasia
      were overlooked in >50% of patients with both abnormal measurements and SNHL.
      Cochlear hypoplasia (< 4.4 mm) had a positive predictive value of 100% for SNHL,
      whereas cochlear hyperplasia and bony island dysplasia were less predictive.
      CONCLUSION: The measurements of coronal cochlear height and axial LSCC bony width
      have excellent reproducibility and identify bony labyrinth abnormalities missed
      by visual inspection alone. In addition, cochlear hypoplasia is highly predictive
      of SNHL. To reliably identify inner ear malformations, measurement of the
      cochlear height and LSCC bony island width, in addition to the vestibular
      aqueduct, should be routinely performed on all temporal bone studies.

PMID- 16885753
TI  - Water may cure patients with Meniere disease.
AB  - OBJECTIVES/HYPOTHESIS: We examined whether sufficient water intake is effective
      in the long-term control of vertigo and hearing activity in patients with Meniere
      disease (MD) for whom conventional therapy has proven unsuccessful. STUDY DESIGN:
      The authors conducted a time-series study with historical control. METHODS:
      Eighteen patients with MD in group 1 drank 35 mL/kg per day of water for 2 years.
      Twenty-nine patients with MD treated with the conventional dietary and diuretic
      therapy for more than 2 years during 1992 to 1999 at the same hospital were
      enrolled in a historical control of group 2. RESULTS: Patients in group 1
      dramatically relieved vertigo and significantly improved in the hearing of the
      worst pure-tone average of three frequencies (0.125, 0.25, and 0.5 kHz) (low PTA)
      during the last 6 months of the study period. In contrast, patients in group 2
      became worse in both the four- (0.5, 1, 2, and 4 kHz) frequency PTA and the low
      PTA, although their vertigo did improve. The number of patients whose hearing
      were improved, unchanged, and worse were 4, 12, and 2 in group 1 and 2, 11, and
      16 in group 2, respectively. CONCLUSION: Deliberate modulation of the intake of
      water may be the simplest and most cost-effective medical treatment for patients
      with MD. Larger studies will be needed to confirm these results in a larger
      patient cohort.

PMID- 16885754
TI  - Intraparotid sentinel lymph node biopsy for head and neck melanoma.
AB  - OBJECTIVE: The objective of this retrospective clinical review was to assess the
      safety and accuracy of intraparotid sentinel node biopsy in patients with
      melanoma. SETTING: This study was conducted at a tertiary referral center.
      PATIENTS: Twenty-eight patients with cutaneous melanoma of the head and neck
      undergoing sentinel lymph node (SLN) biopsy in which the radionuclide localized
      to the parotid gland on preoperative lymphoscintigraphy were studied. METHODS:
      All patients underwent wide local excision of the tumor and intraparotid sentinel
      node biopsy using intraoperative gamma probe localization. RESULTS: There were 25
      men and 3 women ranging in age from 34 to 81 years. The primary site was on the
      auricle in 14 patients: temple, 4; forehead, 5; cheek, 3; and on the neck in 2
      patients, respectively. The mean Breslow thickness was 2.3 mm (range, 0.9-7.0
      mm). In 27 of 28 patients, an intraparotid SLN was identified. In one patient,
      final pathology did not reveal lymphoid tissue despite a high count in the
      parotid tissue excised. Median number of SLN per patient was two. Six patients
      had microscopic metastases in the SLN. In two of these patients, additional
      microscopic lymph node metastases were found in the neck after subsequent formal
      lymphadenectomy. The pathologic staging for the group (n = 14) was: stage 1B, 4;
      2A, 4; stage 2B, 3; and stage 3B, 3 patients, respectively. All patients are
      alive and without evidence of disease (mean follow up, 31 months). There were no
      surgical complications, specifically no patient experienced temporary or
      permanent facial paralysis. CONCLUSION: Intraparotid SLN biopsy for staging
      cutaneous head and neck melanoma is a reliable, accurate, and safe procedure.

PMID- 16885755
TI  - Transoral robotic surgery (TORS) for base of tongue neoplasms.
AB  - OBJECTIVE: To develop a minimally invasive surgical technique for the treatment
      of base of tongue neoplasms using the optical and technical advantages of robotic
      surgical instrumentation. STUDY DESIGN: Ten experimental procedures including
      tongue base exposure and dissections were performed on three cadavers and two
      mongrel dogs. Transoral robotic surgery (TORS) was then performed on three human
      patients with tongue base cancers in a prospective human trial. METHODS: Using
      the da Vinci Surgical Robot (Intuitive Surgical, Inc., Sunnyvale, CA), we
      performed a total of 10 base of tongue resections on edentulous and dentate
      cadavers as well as live mongrel dogs. In the cadaver models, exposure was
      evaluated using three different retractors, the Dingman, Crowe Davis, and FK
      retractors. The three human patients underwent TORS surgery of their tongue base
      cancers under an institutional review board approved prospective clinical trial.
      The ability to identify and preserve or resect key anatomic structures such as
      the glossopharyngeal, hypoglossal, and lingual nerves as well as techniques for
      identifying the lingual artery and achieving hemostasis were developed. RESULTS:
      The da Vinci Surgical Robot provided excellent visualization and enabled removal
      of the posterior one third to one half of the oral tongue in cadavers, dogs, and
      human patients. Among the three retractors evaluated, the FK retractor offered
      the greatest versatility and overall exposure for robotic instrument
      maneuverability. Complete resection to negative surgical margins with excellent
      hemostasis and no complications was achieved in the live patient surgeries.
      CONCLUSIONS: TORS provided excellent three-dimensional visualization and
      instrument access that allowed successful surgical resections from cadaver models
      to human patients. TORS is a novel and minimally invasive approach to tongue
      neoplasms that has significant advantages over classic open surgery or endoscopic
      transoral laser surgery.

PMID- 16885756
TI  - Advanced stage of head and neck cancer at a tertiary-care county hospital.
AB  - BACKGROUND: Public hospitals provide health care for uninsured and medically
      underserved patients in large metropolitan areas. Outcomes for head and neck
      cancer patients within this population are perceived as being worse than outcomes
      for the general population, perhaps because of advanced stage at presentation.
      OBJECTIVE: This study assesses the initial cancer stage in patients with head and
      neck carcinoma presenting to an urban tertiary-care county hospital compared with
      data for the general population. STUDY DESIGN: Prospective study of 209
      consecutive patients newly diagnosed with head and neck cancer by the Division of
      Otolaryngology/Head and Neck Surgery from October 2003 to April 2005. METHODS:
      Clinical and pathologic data were obtained as patients presented and underwent
      treatment. Demographic data were obtained retrospectively. Staging analysis was
      performed on 186 patients with squamous cell carcinoma. Normative data were
      obtained from the National Cancer Database. RESULTS: The mean age was 55, with a
      4:1 male to female ratio. Over 95% of patients reported being unemployed. The
      racial composition was white 27%, African American 52%, Hispanic 11%, Asian 7%,
      and 3% "other." Staging revealed that 68% of patients were stage IV, and 85%
      would be considered "advanced" disease (stage III/IV). This is significantly
      worse than what national data demonstrates, where only 39% are stage IV, and 55%
      have advanced stage of disease at presentation. CONCLUSION: Although the
      perceived poor outcome of uninsured and underserved cancer patients is
      multifactorial, advanced stage at presentation is a critical factor. These
      statistics demonstrate the need for increased patient education and screening for
      this underserved population as an initial step to improve outcome.

PMID- 16885757
TI  - Activated osteoclasts with CD51/61 expression in otosclerosis.
AB  - HYPOTHESIS: Stapes ankylosis is supposed to be a disease with variable
      histopathology caused by otosclerosis or pseudo-otosclerosis. Persistent measles
      virus infection of the otic capsule could induce reactivation of quiescent
      embryonic osteoclasts in otosclerosis. BACKGROUND: Presence of measles virus RNA
      was demonstrated in the footplates of otosclerotic patients by reverse
      transcription polymerase chain reaction (RT-PCR). Histology of active
      otosclerosis is featured by the presence of numerous osteoclasts with unknown
      phenotype. METHODS: Nucleic acid was extracted from stapes footplates of
      clinically otosclerotic patients (n = 261). Genomic RNA of measles virus was
      amplified by RT-PCR. Amplification results were correlated to postoperative
      histologic and CD51/61 specific immunohistologic findings. A parallel alcalic
      phosphatase activity assessment was performed to evaluate the metabolic activity
      of osteoclasts in each section. RESULTS: Among 261 stapes fixation cases, 175
      otosclerotic stapes contained measles virus RNA. Histology for virus negative
      stapes (n = 86) represented nonotosclerotic, degenerative disorders.
      Histologically confirmed otosclerosis was featured by the presence of osteoclasts
      with renewed, embryonic phenotype. In otosclerosis, alcalic phosphatase activity
      was significantly higher compared with nonotosclerotic stapes ankylosis (P <
      .001). CONCLUSION: The presence of CD51/61 positive osteoclasts in otosclerotic
      bone containing viral sequences provides the basis for an inflammatory bone
      remodeling disorder. Otosclerosis is a disease caused by persistent measles virus
      infection and reactivation of resting embryonic osteoclasts in the otic capsule.

PMID- 16885758
TI  - Comparison of oral versus rectal administration of acetaminophen with codeine in
      postoperative pediatric adenotonsillectomy patients.
AB  - OBJECTIVE: To examine whether acetaminophen with codeine administered per rectum
      is an effective alternative for pain control compared with oral administration
      after an adenotonsillectomy. STUDY DESIGN: A prospective, randomized control
      study. METHODS: Seventy-five children aged 1 to 5 were recruited for this study.
      Each child was assigned randomly to receive either rectal or oral postoperative
      pain medication. A journal with eight questions was kept for 10 days after the
      operation, and an overall survey of five questions was filled out at the first
      postoperative visit. RESULTS: Postoperative pain was adequately controlled in
      those patients receiving suppositories when compared with those patients
      receiving oral pain medication. Adverse effects and total number of doses given
      per day were similar. Parents found the suppositories easy to administer, and
      more parents would switch or consider switching from oral pain medication to
      suppositories if given the choice. CONCLUSIONS: The suppositories achieved
      equivalent pain control as oral medication with few side effects and good
      tolerance. Furthermore, many parents preferred the suppositories to oral
      medication in maintaining postoperative pain control because of ease of
      administration. If given the choice for future surgeries, many parents would
      switch or consider switching from oral pain medication to suppositories.

PMID- 16885759
TI  - Coordination of swallowing and respiration in normal sequential cup swallows.
AB  - OBJECTIVES: To establish normative data on laryngeal vestibular closure patterns
      and respiratory phase patterns during sequential cup swallows in healthy adults.
      STUDY DESIGN: Cross-sectional study. METHODS: Combined videofluoroscopic and
      respiratory phase recordings were analyzed in 70 healthy adults during 50 mL
      sequential liquid cup swallows. The following dependent variables were measured
      offline from the digitized recordings: 1) number of swallows, 2) number of
      ingestion cycles (IC) (period of sustained apnea including 1 or more swallows),
      3) opening of the laryngeal vestibule after each swallow, and 4) respiratory
      phase surrounding each IC. Patients were grouped according to the position of the
      larynx after each swallow. RESULTS: The mean number of swallows was 4.35, and the
      mean number of ICs was 3.28. Laryngeal vestibular opening after swallows was
      categorized into three groups: Always Open = 67.1%, Mixed (Open and Closed) =
      31.4%, Always Closed = 1.4%. Statistical differences were not found in laryngeal
      opening pattern by age or sex, but the Always Open group had fewer swallows (4.02
      vs. 5.23, P = .008) and a greater number of ICs (3.62 vs. 2.41, P = .001) than
      the Mixed Group. Respiratory phase after IC was expiration in 79% and inspiration
      in 21%. CONCLUSIONS: Normal patterns of laryngeal vestibular closure and
      respiratory phase coordination during sequential swallowing have been described
      for the first time. The high occurrence of inspiration and laryngeal vestibular
      opening that surrounds sequential liquid cup swallows when compared with previous
      findings in single, discrete swallows may place patients with swallowing
      disorders at greater risk during this task.

PMID- 16885760
TI  - Complications of surgery for nasal polyposis and chronic rhinosinusitis: the
      results of a national audit in England and Wales.
AB  - OBJECTIVE: The objective of this study was to determine the rate of complications
      of surgery for nasal polyposis and chronic rhinosinusitis as well as their risk
      factors. STUDY DESIGN, SETTING, PARTICIPANTS, AND OUTCOME MEASURES: The authors
      conducted a prospective study of 3,128 patients who underwent sinonasal surgery
      during 2000 and 2001 in 87 National Health Service hospitals in England and
      Wales. Patients completed a preoperative questionnaire that included the Sino
      Nasal Outcome Test, a measure of sinonasal symptoms severity and health-related
      quality of life. Surgeons provided information about polyp extent, opacity of the
      sinuses on computed tomography (Lund-Mackay score), comorbidity (American Society
      of Anesthesiologists score), and the occurrence of perioperative complications.
      RESULTS: Major complications (orbital or intracranial complications, bleeding
      requiring ligation or orbital decompression, or return to the operating room)
      occurred in 11 patients (0.4%). Minor complications (all other untoward events)
      occurred in 207 patients (6.6%). Most frequently reported minor complications
      were excessive perioperative hemorrhage bleeding (5.0%) as well as postoperative
      hemorrhage requiring treatment (0.8%). Multivariate analysis indicated that the
      complication rate was linked to the extent of disease measured in terms of
      symptom severity and health-related quality of life, the extent of polyposis,
      level of opacity of the sinuses on computed tomography, and the presence of
      comorbidity, but not surgical characteristics (extent of surgery, use of
      endoscope or microdebrider, grade of surgeon, and adjunctive turbinate surgery).
      CONCLUSIONS: The risk of complications depended on patient characteristics rather
      than on the surgical technique used. Measures of the extent of disease and
      comorbidity may help in identifying patients at high risk of complications.

PMID- 16885761
TI  - Divergence of fine and gross motor skills in prelingually deaf children:
      implications for cochlear implantation.
AB  - OBJECTIVE: The objective of this study was to assess relations between fine and
      gross motor development and spoken language processing skills in pediatric
      cochlear implant users. STUDY DESIGN: The authors conducted a retrospective
      analysis of longitudinal data. METHODS: Prelingually deaf children who received a
      cochlear implant before age 5 and had no known developmental delay or cognitive
      impairment were included in the study. Fine and gross motor development were
      assessed before implantation using the Vineland Adaptive Behavioral Scales, a
      standardized parental report of adaptive behavior. Fine and gross motor scores
      reflected a given child's motor functioning with respect to a normative sample of
      typically developing, normal-hearing children. Relations between these preimplant
      scores and postimplant spoken language outcomes were assessed. RESULTS: In
      general, gross motor scores were found to be positively related to chronologic
      age, whereas the opposite trend was observed for fine motor scores. Fine motor
      scores were more strongly correlated with postimplant expressive and receptive
      language scores than gross motor scores. CONCLUSIONS: Our findings suggest a
      disassociation between fine and gross motor development in prelingually deaf
      children: fine motor skills, in contrast to gross motor skills, tend to be
      delayed as the prelingually deaf children get older. These findings provide new
      knowledge about the links between motor and spoken language development and
      suggest that auditory deprivation may lead to atypical development of certain
      motor and language skills that share common cortical processing resources.

PMID- 16885762
TI  - Ultrasound-guided laser-induced thermal therapy of malignant cervical adenopathy.
AB  - OBJECTIVES: Laser-induced thermal therapy (LITT) for cancer is a technique
      whereby a source of energy (laser, radiofrequency, ultrasonic, cryoenergy, and so
      on) is directly applied into a tumor at various depths. Recent studies have
      demonstrated the efficiency of ultrasound (UTZ) and magnetic resonance imaging
      (MRI) for real- or "near" real-time tumor and vessel identification as well as
      monitoring and quantifying energy-induced tissue damage. The objective of this
      study is to report UCLA's experience using UTZ monitoring of Nd:YAG laser thermal
      ablation of malignant cervical adenopathy in a phase II study. STUDY DESIGN: The
      authors conducted a retrospective study of patients treated at a tertiary medical
      center. METHODS: Forty-seven patients with a total of 55 neck tumors were treated
      on an outpatient basis in the operating room using UTZ for image-guided laser
      interstitial thermal therapy. Laser energy was delivered through an SLT Nd:YAG
      laser powered at 30 W (power density: 2,200 J/cm). RESULTS: Eleven patients had a
      complete response ranging from 5.5 to 90 months (mean, 22.1 months). Based on the
      findings of this study, it was possible to show that proximity to the carotid
      artery was the most relevant factor in projecting patient survival. Patients'
      individual treatment analysis and final outcome are further discussed.
      CONCLUSIONS: LITT ablation of malignant cervical adenopathy was considered safe
      and feasible. No intraoperative complications occurred. Further development of
      this technique applying laser energy delivery to mathematical imaging models
      should lead to more effective tumor palliation as an alternative to surgery.

PMID- 16885763
TI  - Use of Er,Cr:YSGG versus standard lasers in laser assisted uvulopalatoplasty for
      treatment of snoring.
AB  - OBJECTIVES: The aim of this study was to compare the effectiveness of the
      Er,Cr:YSGG (Waterlase) laser with KTP and CO2 lasers in laser assisted
      uvulopalatoplasty (LAUP) for treatment of snoring. STUDY DESIGN: This is a
      prospective study of 63 patients who were treated for snoring by LAUP either with
      Er,Cr:YSGG (n = 21) or with KTP (n = 21) or CO2 lasers (n = 21). Histologic
      analysis was performed, and the effects of KTP and Waterlase on soft tissue were
      compared. METHODS: Patients were examined by an ENT surgeon and tested with
      polysomnography. Probands who suffered from obstructive sleep apnea or had an
      apnea-hypopnea index of 15 or greater were excluded from the study. The remaining
      patients were assigned to either Er,Cr:YSGG, KTP, or CO2 laser therapy. The three
      lasers were compared from a postoperative recovery point of view by
      immunohistochemical examination. RESULTS: Pain medications were used on average
      for 4.1, 6.5, and 10.1 days, and the times to return to normal diet were on
      average 4.5, 6.8, and 8.6 days in the Er,Cr:YSGG, KTP, and CO2 groups,
      respectively. Two cases of bleeding were observed in the CO2 group. Foreign body
      sensation occurred in 14%, 19%, and 19% of subjects in the Er,Cr:YSGG, KTP, and
      CO2 groups, respectively. Velopharyngeal insufficiency was noticed in one KTP
      treated patient; however, it was transient. Snoring and apnea-hypopnea index was
      significantly reduced in all groups. Significantly larger coagulation of soft
      tissue was found in the KTP group than in the Waterlase group. CONCLUSIONS:
      Patients treated with Waterlase recovered more quickly in comparison with
      patients in the KTP and CO2 groups, which was confirmed by immunohistochemical
      findings. The laser techniques did not differ in effectiveness.

PMID- 16885764
TI  - Massive enlargement of the nasolacrimal canal causing epiphora and chronic
      maxillary sinusitis.
AB  - OBJECTIVES: Enlargement of the nasolacrimal canal (NLC) is a rare anatomic
      variant. We present the first report of a massively dilated NLC causing epiphora
      and chronic sinusitis. METHODS: The authors conducted a literature review and
      case report. RESULTS: A 65-year-old man with refractory sinonasal symptoms and a
      remote history of a dacryocystorhinostomy was found to have a massively dilated,
      air-filled NLC. Using a combined endoscopic transnasal and endoscope-assisted
      Caldwell-Luc approach, the posterolateral wall of the NLC was removed. The
      patient's symptoms were improved 10 months postoperatively. CONCLUSIONS: Symptoms
      suggestive of nasolacrimal dysfunction should prompt a search for potential
      sinonasal pathology.

PMID- 16885765
TI  - Loss of trigeminal sensitivity reduces olfactory function.
AB  - The trigeminal and olfactory nerves share overlapping innervation areas in the
      nasal cavity and seem to work in an interactive way. Loss of olfactory function
      leads to a decreased trigeminal sensitivity, as shown in anosmic subjects. To
      report the impact of disturbed trigeminal sensitivity on the olfactory function,
      we present a patient with unilateral loss of trigeminal function resulting from a
      meningeoma. Thresholds to a selective olfactory stimulus were elevated by a
      factor of 64 on the affected side. Recordings of event-related potentials in
      response to olfactory stimuli showed a significantly reduced response on the
      affected side. This report indicates that loss of trigeminal function may affect
      the sense of smell.

PMID- 16885766
TI  - Office-based digital video endoscopy in otolaryngology.

PMID- 16885767
TI  - The difficulty of tending to the suffering terminal patient: an exploration of
      euthanasia and physician-assisted suicide.

PMID- 16885768
TI  - Vocal cord paralysis after laryngeal mask airway ventilation.

PMID- 16885770
TI  - Effectiveness of low-dose indinavir/ritonavir at 400/100 mg twice a day with 2
      nucleoside reverse transcriptase inhibitors in nonnucleoside reverse
      transcriptase inhibitor-experienced HIV-infected patients in India: 1-year follow
      up.

PMID- 16885771
TI  - Independent association of hygiene, socioeconomic status, and circumcision with
      reduced risk of HIV infection among Kenyan men.
AB  - Among Kenyan men recruited as sex partners of women with genital symptoms, 22 of
      150 were HIV seropositive. Because male HIV infection and male hygiene were
      unexpectedly found to be associated with each other, we examined the relationship
      of 5 hygiene variables with HIV infection in the men in a principal components
      analysis, controlling for socioeconomic status and other potential confounders.
      By multivariate analyses, HIV infection in men was not only independently
      associated with previous illness (odds ratio [OR], 5.1; 95% confidence interval
      [CI], 1.4-19.1) and inversely associated with being circumcised (OR, 0.12; 95%
      CI, 0.02-0.91), but also independently associated with a combined measure of
      hygiene (OR, 0.41; 95% CI, 0.19-0.90).

PMID- 16885772
TI  - Mortality and morbidity among postpartum HIV-positive and HIV-negative women in
      Zimbabwe: risk factors, causes, and impact of single-dose postpartum vitamin A
      supplementation.
AB  - BACKGROUND: Vitamin A deficiency is common among women in resource-poor countries
      and is associated with greater mortality during HIV. METHODS: Fourteen thousand
      one hundred ten mothers were tested for HIV and randomly administered 400,000 IU
      vitamin A or placebo at less than 96 hours postpartum. The effects of vitamin A
      and HIV status on mortality, health care utilization, and serum retinol were
      evaluated. RESULTS: Four thousand four hundred ninety-five (31.9%) mothers tested
      HIV positive. Mortality at 24 months was 2.3 per 1000 person-years and 38.3 per
      1000 person-years in HIV-negative and HIV-positive women, respectively. Vitamin A
      had no effect on mortality. Tuberculosis was the most common cause of death, and
      nearly all tuberculosis-associated deaths were among HIV-positive women. Among
      HIV-positive women, vitamin A had no effect on rates of hospitalization or
      overall sick clinic visits, but did reduce clinic visits for malaria, cracked and
      bleeding nipples, pelvic inflammatory disease, and vaginal infection. Among HIV
      negative women, serum retinol was responsive to vitamin A, but low serum retinol
      was rare. Among HIV-positive women, serum retinol was largely unresponsive to
      vitamin A, and regardless of treatment group, the entire serum retinol
      distribution was shifted 25% less than that of HIV-negative women 6 weeks after
      dosing. CONCLUSIONS: Single-dose postpartum vitamin A supplementation had no
      effect on maternal mortality, perhaps because vitamin A status was adequate in
      HIV-negative women and apparently unresponsive to supplementation in HIV-positive
      women.

PMID- 16885773
TI  - Epidemiology of HIV-1 infection in agricultural plantation residents in Kericho,
      Kenya: preparation for vaccine feasibility studies.
AB  - A cross-sectional study was performed to determine the prevalence and risk
      factors for HIV-1 infection among agricultural plantation residents in Kericho,
      Kenya. Volunteers were recruited, interviewed, and phlebotomized for HIV-1
      serologic testing. Sex-specific adjusted odds ratios were estimated using
      logistic regression. The overall HIV-1 prevalence was 9.9% (81/820), with
      prevalence in women more than twice that in men (17.4% vs 8.0%, P=0.001). Among
      men, elevated HIV-1 prevalence was seen with increasing age, peaking in those
      older than 30 years (10.3%), marriage (10.4%), Luo tribe affiliation (23.5%),
      employment (8.9%), travel (11.0%), and being uncircumcised (29.2%). Among women,
      elevated HIV-1 prevalence was seen in those with no formal education (36.8%) and
      those who received goods in exchange for sex (36.0%). More than 97% of volunteers
      expressed a willingness to participate in future HIV-1 studies requiring
      semiannual visits. HIV prevention efforts have been implemented, along with
      further research to characterize this population for future cohort feasibility
      studies and HIV-1 vaccine efficacy trials.

PMID- 16885774
TI  - Sexually transmitted infection service use and risk factors for HIV infection
      among female sex workers in Georgetown, Guyana.
AB  - OBJECTIVES: To identify risk factors for HIV and sexually transmitted infection
      (STI) service use patterns among female sex workers in Georgetown, Guyana.
      DESIGN: A cross-sectional study was conducted among 299 female commercial sex
      workers. METHODS: HIV prevalence was assessed using an oral fluid test, and
      sociodemographic and behavioral data by interview administered by sex workers and
      women's group members. RESULTS: HIV prevalence was 30.6% [95% confidence interval
      (CI) 24.9-36.3]. Multivariate logistic regression found a significant association
      between HIV infection and having a vaginal ulcer in the last 12 months [odds
      ratio (OR) 4.0, CI 1.4-12.0]. Having had a vaginal ulcer was associated with use
      of cocaine. Multivariate logistic regression on STI service use variables found
      significant associations between HIV infection and getting condoms from public
      sector STI services (OR 3.1, CI 1.6-5.8), not going back for HIV test results (OR
      3.4, CI 1.1-10.1), and last getting tested for HIV more than 6 months ago (OR
      2.8, CI 1.3-6.2). CONCLUSIONS: An active program of screening and treatment of
      ulcerative STIs should be combined with substance abuse services for sex workers
      (SW). Condom promotion services are reaching SW at high risk, but HIV stigma may
      prevent SW at high risk from accessing HIV test results.

PMID- 16885775
TI  - Undiagnosed HIV infection and couple HIV discordance among household members of
      HIV-infected people receiving antiretroviral therapy in Uganda.
AB  - INTRODUCTION: Systematic efforts to identify HIV-infected members and HIV
      discordant couples in households of individuals taking antiretroviral therapy
      (ART) could theoretically reduce HIV transmission and improve ART adherence.
      METHODS: We enrolled HIV-infected clients of an AIDS support organization in a
      randomized evaluation of different ART monitoring regimens that offered home
      based ART care to them and their clinically eligible household members. At
      baseline, counselors visited participants' homes and offered voluntary counseling
      and testing (VCT) to all household members. We assessed uptake, HIV prevalence,
      HIV discordance, and rate of ART eligibility. RESULTS: Of the 2373 household
      members, 2348 (99%) accepted VCT. HIV prevalence among household members was 7.5%
      and varied by age with 9.5% among children aged 0 to 5 years, 2.9% among persons
      aged 6 to 24 years, and 37.1% among adults aged 25 to 44 years. Of the household
      members with HIV, 74% had never been previously tested, and 39% of these were
      clinically eligible for ART. Of the 120 spouses of ART patients that were tested
      for HIV, 52 (43%) were HIV negative, and of these, 99% had not been previously
      tested. CONCLUSIONS: Provision of home-based VCT to household members of people
      initiating ART was well accepted and resulted in the detection of a large number
      of previously undiagnosed HIV infections and HIV-discordant relationships.

PMID- 16885776
TI  - Rapid emergence of enfuvirtide resistance in HIV-1-infected patients: results of
      a clonal analysis.
AB  - OBJECTIVES: To study the dynamics of enfuvirtide (T-20) resistance development in
      HIV-1-infected subjects. PATIENTS AND METHODS: Clonal analysis of gp41 sequences
      was performed on serial samples obtained from HIV-1-infected subjects with early
      virologic failure of T-20-based regimens. RESULTS: Enfuvirtide resistance
      mutations at codons 36 to 45 in the first heptad repeat of gp41 emerged within 2
      weeks in most subjects and were associated with the return of plasma HIV-1 RNA
      level toward baseline by weeks 4 to 8. Mutations at codons 36 (G36E, G36D, or
      G36S) and 38 (V38A, V38G, or V38M) were the most commonly detected resistance
      mutations at week 2. Mutations at codons 40 (Q40H) and 43 (N43D) were more
      prevalent at week 4 than at week 2 and seemed to emerge more slowly than
      mutations at codons 36 and 38. CONCLUSIONS: The rapid emergence of mutations
      associated with T-20 resistance in the absence of a fully suppressive
      antiretroviral regimen demonstrates a low genetic barrier to resistance and
      underscores the importance of combining T-20 with other active drugs when
      constructing regimens for highly treatment-experienced patients.

PMID- 16885777
TI  - HIV-1 drug resistance genotype results in patients with plasma samples with HIV-1
      RNA levels less than 75 copies/mL.
AB  - HIV-1 genotypic resistance test results were obtained on clinical samples from
      116 patients with plasma HIV-1 RNA levels of less than 75 copies/mL. Genotype
      validity was confirmed in 49 of 50 patients with a previous or follow-up
      genotype. The belief that genotypic resistance testing is unreliable in samples
      with low-level viremia should be reassessed.

PMID- 16885778
TI  - Survival rate and risk factors of mortality among HIV/tuberculosis-coinfected
      patients with and without antiretroviral therapy.
AB  - BACKGROUND: The impact of antiretroviral therapy (ART) on survival among patients
      coinfected with HIV and tuberculosis (TB) has not been well established. METHODS:
      A retrospective cohort study was conducted among HIV-infected patients with TB
      between January 2000 and December 2004. Patients were categorized into ART+ group
      (received ART) and ART- group (did not receive ART) and were followed until April
      2005. RESULTS: A total of 1003 patients were identified; 411 in ART+ group and
      592 in ART- group. Median (interquartile range) CD4 count was 53 (20-129)
      cells/mm3. Survival rates at 1, 2, and 3 years after TB diagnosis were 96.1%,
      94.0%, and 87.7% for ART+ group and 44.4%, 19.2%, and 9.3% for ART- group (log
      rank test, P<0.001). Cox proportional hazard model showed that ART was associated
      with lower mortality rate; gastrointestinal TB and multidrug resistant TB were
      associated with higher mortality rate (P<0.05). Among patients in ART+ group, the
      patients who delayed ART>or=6 months after TB diagnosis had a higher mortality
      rate than those who initiated ART<6 months after TB diagnosis (P 0.018, hazard
      ratio=2.651, 95% confidence interval=1.152-6.102). CONCLUSIONS: Antiretroviral
      therapy substantially reduces mortality rate among HIV/TB-coinfected patients.
      Initiation of ART within 6 months of TB diagnosis is associated with greater
      survival.

PMID- 16885779
TI  - Increased body mass index does not alter response to initial highly active
      antiretroviral therapy in HIV-1-infected patients.
AB  - BACKGROUND: Body mass index (BMI) can influence drug metabolism, thus affecting
      efficacy and risk for toxicities. Hypothesizing that persons with an increased
      BMI and larger volumes of distribution may experience a suboptimal response to
      highly active antiretroviral therapy (HAART), we evaluated the effect of BMI on
      virologic and immunologic response in previously ART-naive patients initiating
      therapy. METHODS: Using data from the HIV Outpatient Study, we analyzed the
      statistical association of BMI and other selected demographic variables with
      achieving an undetectable viral load and experiencing a CD4 cell count increase
      of more than 100 cell/microL after 3 to 9 months of therapy among antiretroviral
      naive patients initiating HAART. RESULTS: Among 711 patients included in
      analysis, 43% had a BMI of more than 25 (overweight-obese). Higher BMI was
      associated with being female, having black or Hispanic race/ethnicity, being
      heterosexual, and using injection drugs (all P<0.001). The patients in BMI groups
      did not differ significantly by baseline CD4 cell count or the duration of the
      initial HAART regimen. Although median baseline viral loads were significantly
      lower in obese participants (P=0.008), overweight or obese BMI did not
      significantly alter the likelihood of achieving an undetectable viral load and a
      CD4 cell count increase of more than 100 cells/microL compared with normal weight
      persons. CONCLUSION: A substantial proportion of HIV-infected outpatients in this
      cohort were overweight or obese. Increased BMI was not associated with decreased
      virologic and immunologic responses to initial HAART. Responses were equivalent
      and within expected ranges between normal weight patients, overweight patients,
      and obese patients at 3 to 9 months of observation.

PMID- 16885780
TI  - A reliable and inexpensive EasyCD4 assay for monitoring HIV-infected individuals
      in resource-limited settings.
AB  - Serial measurements of absolute CD4+ T-lymphocyte counts are required to initiate
      and gauge response to therapy and monitor disease progression. Hence, there is an
      urgent need to evaluate the accuracy and validity of low-cost CD4+ T-cell count
      assays. Tripotassium EDTA blood specimens from HIV-infected individuals were
      studied using a novel flow cytometric assay (EasyCD4 assay; Guava Technologies,
      Hayward, CA) in comparison with standard flow cytometry (FACSCount; Becton
      Dickinson Immunocytometry Systems, San Jose, CA). The sensitivity, specificity
      value by EasyCD4 assay in enumerating absolute CD4+ T-cell counts of less than
      200 cells/microL were 95% and 100%, respectively. Bland-Altman analysis showed
      close agreement, with the EasyCD4 assay yielding CD4+ T-cell counts a mean
      difference of -26 cells/microL (95% confidence interval, -96 to 44 cells/microL)
      higher than by flow cytometry. Our data suggest that EasyCD4 assay could be a
      useful alternative assay to conventional flow cytometry, may be appropriate for
      use in resource-limited settings.

PMID- 16885781
TI  - Emergence of antiretroviral therapy resistance-associated primary mutations among
      drug-naive HIV-1-infected individuals in rural western Cameroon.
AB  - The prevalence of antiretroviral therapy (ART) resistance-associated mutations
      among HIV-1 strains in western Cameroon was evaluated by genotypically analyzing
      strains isolated from drug-naive individuals. Proviral DNA was extracted from 54
      blood samples and amplified by polymerase chain reaction of protease, reverse
      transcriptase, integrase, and envelope genes. At least 4 clones per sample were
      analyzed. Of 54 HIV-1 strains, 45 (83.3%) had a concordant subtype or circulating
      recombinant form (CRF) designation: 40 CRF02_AG, 2 subtype A1, 2 G, and 1 F2. The
      remaining 9 (16.7%) had a discordant subtype: 6 subtype A1/CRF02_AG, 2 D/CRF02,
      and 1 G/CRF02. Protease inhibitor-associated primary resistance mutations were
      found in 4 (7.4%) cases: M46L with full clones in 1 case, and M46I, M46L, and
      V82A as minor populations in 1 case each. Reverse transcriptase inhibitor
      associated primary resistance mutations were found in 5 (9.8%) samples: Y188C in
      2 cases, and L100I, M184V, and V75I in 1 case each, although all of these
      mutations were found as minor populations. This is one of the first reports of
      the emergence of primary ART resistance mutations among drug-naive, non-B subtype
      HIV-1-infected individuals in Cameroon. Follow-up studies should be conducted to
      assess whether these drug-resistant mutants found as minor populations might
      impact future ART.

PMID- 16885782
TI  - Cochlear otosclerosis.

PMID- 16885783
TI  - The effect of organ of corti loss on ganglion cell survival in humans.
AB  - HYPOTHESIS: Severe spiral ganglion cell loss does not necessarily follow loss of
      hair cells or supporting cells in humans. BACKGROUND: Despite some publications
      to the contrary, statements that loss of hair cells and/or supporting cells of
      the organ of Corti results in a severe loss of spiral ganglion cells in humans
      still appear in the literature, especially in respect to cochlear implants. This
      assumption is apparently based on studies in animals or cell culture and not from
      studies of human temporal bones. METHODS: Morphological analysis of archival
      temporal bones with microscopic and statistical analysis of ganglion cell, hair
      cell, and supporting cell populations was performed in 33 ears with total hearing
      losses of varying causes and durations of deafness. None of the ears had
      remaining hair cells. Six ears had had cochlear implants. RESULTS: Ganglion cell
      counts ranging from 2,889 to 34,299 and the corresponding percentage of remaining
      ganglion cells based on age-normative data were not significantly related to the
      duration of hearing loss (r = -0.13 and 0.02, respectively, p > 0.05) or to
      remaining supporting cell populations (r's from 0.15 to 0.27, p > 0.05). More
      than half of ears (51.5%) had ganglion cell counts within two standard deviations
      of age-normative means. Mean ganglion cell counts and percentage of remaining
      ganglion cells of ears with surviving peripheral processes (dendrites) did not
      differ significantly from those of ears with no peripheral processes. CONCLUSION:
      The loss of hair and supporting cells in the organ of Corti in humans does not
      necessarily result in as significant a loss of spiral ganglion cells as has been
      reported animals. In fact, our results suggest that ganglion cell loss may be a
      primary concomitant loss due to the disease process.

PMID- 16885784
TI  - Lateral semicircular canal and vertigo in patients with large vestibular aqueduct
      syndrome.
AB  - OBJECTIVE: To evaluate the hypothesis that there are differences in the
      morphology of the lateral semicircular canal (LSCC) between patients with large
      vestibular aqueduct syndrome (LVAS) and control subjects and to investigate the
      clinical implications of these differences. STUDY DESIGN: Retrospective case
      review. SETTING: Tertiary referral center. PATIENTS: Nine patients (two male
      patients and seven female patients; age range, 8-54 yr) with LVAS (one patient
      had unilateral LVAS, and eight patients had bilateral LVAS). Five patients had
      vertigo, and four patients, including the one with unilateral LVAS, did not have
      vertigo. MAIN OUTCOME MEASURES: The area of the LSCC was traced on the magnetic
      resonance imaging console and compared between LVAS patients and 12 control
      subjects who did not have sensorineural hearing loss. The LSCC fluid-containing
      area was divided by the sum of the LSCC inner area and the LSCC fluid-containing
      area for evaluation of the degree of the LSCC dysplasia. RESULTS: The LSCC fluid
      containing ratio was significantly larger in LVAS patients than in control
      subjects. Moreover, the LSCC fluid-containing ratio was significantly larger in
      the eight ears with vertigo than in the nine ears without vertigo. There was no
      relationship between hearing level and the LSCC fluid-containing ratio.
      CONCLUSION: Patients with LVAS may have disturbed morphogenesis of both
      membranous and bony labyrinths. Our results reveal that the morphology of
      semicircular canals is clinically associated with vertigo.

PMID- 16885785
TI  - Audiometric analyses confirm a cochlear component, disproportional to age, in
      stapedial otosclerosis.
AB  - OBJECTIVE: To report the preoperative audiometric profile of surgically confirmed
      otosclerosis. STUDY DESIGN: Retrospective, multicenter study. SETTING: Four
      tertiary referral centers. PATIENTS: One thousand sixty-four surgically confirmed
      patients with otosclerosis. INTERVENTIONS: Therapeutic ear surgery for hearing
      improvement. MAIN OUTCOME MEASURES: Preoperative audiometric air conduction (AC)
      and bone conduction (BC) hearing thresholds were obtained retrospectively for
      1064 patients with otosclerosis. A cross-sectional multiple linear regression
      analysis was performed on audiometric data of affected ears. Influences of age
      and sex were analyzed and age-related typical audiograms were created. Bone
      conduction thresholds were corrected for Carhart effect and presbyacusis; in
      addition, we tested to see if separate cochlear otosclerosis component existed.
      Corrected thresholds were than analyzed separately for progression of cochlear
      otosclerosis. RESULTS: The study population consisted of 35% men and 65% women
      (mean age, 44 yr). The mean pure-tone average at 0.5, 1, and 2 kHz was 57 dB
      hearing level. Multiple linear regression analysis showed significant progression
      for all measured AC and BC thresholds. The average annual threshold deterioration
      for AC was 0.45 dB/yr and the annual threshold deterioration for BC was 0.37
      dB/yr. The average annual gap expansion was 0.08 dB/year. The corrected BC
      thresholds for Carhart effect and presbyacusis remained significantly different
      from zero, but only showed progression at 2 kHz. CONCLUSION: The preoperative
      audiological profile of otosclerosis is described. There is a significant
      sensorineural component in patients with otosclerosis planned for stapedotomy,
      which is worse than age-related hearing loss by itself. Deterioration rates of AC
      and BC thresholds have been reported, which can be helpful in clinical practice
      and might also guide the characterization of allegedly different phenotypes for
      familial and sporadic otosclerosis.

PMID- 16885786
TI  - Unilateral deafness after acoustic neuroma surgery: subjective hearing handicap
      and the effect of the bone-anchored hearing aid.
AB  - OBJECTIVE: To evaluate the subjective hearing handicap in patients with
      unilateral deafness after acoustic neuroma surgery and the effect of the Bone
      anchored Hearing Aid (BAHA) on test band. STUDY DESIGN: Fifty-nine consecutive
      patients with unilateral deafness after translabyrintine removal of an acoustic
      neuroma, treated in Denmark in 2001 and 2002, were included. The patients were
      asked to complete a questionnaire, which addressed the subjective handicap of
      unilateral deafness; 90% responded. These patients were invited to test the BAHA
      on test band, and the subjective and objective effects were recorded. RESULTS:
      Eighty percent of the patients thought that they had a subjective hearing
      handicap of some significance. However, only 50% accepted the invitation to test
      the BAHA. The overall subjective effect was positive, and a significant
      improvement in speech discrimination in noise with the BAHA was demonstrated.
      After the test, however, only about 50%, that is, 25% of all patients wished
      implantation for BAHA treatment. CONCLUSION: This study shows that unilateral
      deafness after acoustic neuroma surgery is thought as a handicap in most of the
      patients and confirms that treatment with the BAHA has positive subjective
      effects and improves speech discrimination in noise. However, only 25% of the
      patients wished implantation for BAHA treatment. The implications of these
      findings are discussed. Data from centers that perform simultaneous acoustic
      neuroma surgery and implantation for BAHA are necessary for firm conclusions.

PMID- 16885787
TI  - Comparison between clinical diagnoses and autopsy findings in a pediatric
      intensive care unit in Sao Paulo, Brazil.
AB  - OBJECTIVE: To verify the frequency of discrepancies between clinical diagnoses
      and autopsy findings in patients from a pediatric intensive care unit and to look
      for predictive factors of the discrepancies. DESIGN: Prospective evaluation
      performed between September 1996 and December 1998. SETTING: Eight-bed pediatric
      intensive care unit of a university hospital. PATIENTS: One hundred and two
      autopsies. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Disagreements
      between autopsy and antemortem diagnoses were classified as proposed by Goldman.
      Patient age, presence of underlying disease, and length of stay were studied as
      possible predictive factors for diagnosis discrepancies. During the 28 months of
      study there were 779 admissions to the pediatric intensive care unit; the death
      rate was 26% and the autopsy rate was 55%. One hundred and two of 114 (89.5%)
      autopsies were evaluated. The median age of the patients was 21 months, and 85%
      of them had a previous underlying disease. One third of patients died before 24
      hrs of admission to the pediatric intensive care unit. The autopsy revealed
      unexpected findings in 73 study patients (72%), 33 of which were related to
      "major diagnoses" (Goldman's classes I or II), either causes of death or main
      underlying disease. In 12 patients (12%), the correct diagnosis, if known before
      death, might have led to a change in the patient's therapy or outcome (class I).
      Unexpected findings in this group included viral or fungal infection and
      pulmonary embolism. None of the possible predictive factors that we studied
      showed significant statistical association between clinical and autopsy
      discrepant diagnoses in the univariate analysis. CONCLUSIONS: Although diagnoses
      of both cause of death and underlying disease were accurate in most cases before
      death, some autopsies revealed findings that would have changed intensive care
      unit therapy. Nonbacterial infections and pulmonary thromboembolism should always
      be considered when managing critically ill patients with underlying disease.
      Autopsy examinations continue to provide important information, especially in the
      pediatric intensive care unit setting, despite the advances in diagnostic
      technology.

PMID- 16885788
TI  - Early experience with Levosimendan in children with ventricular dysfunction.
AB  - OBJECTIVE: To describe our preliminary experience with Levosimendan, a new
      calcium-sensitizing agent in critically unwell infants and children with severe
      heart failure. DESIGN: Retrospective cohort analysis. SETTING: Pediatric
      intensive care unit. PATIENTS: Fifteen children aged 7 days to 18 yrs (median age
      38 months) with severe myocardial dysfunction secondary to end-stage heart
      failure, or acute heart failure, who were inotrope-dependent (requiring at least
      one catecholamine). INTERVENTIONS: A single dose (bolus and intravenous infusion
      over 24-48 hrs) of Levosimendan was given under continuous hemodynamic monitoring
      in our intensive care unit. Eleven children received a single dose, three
      children received two doses, and one child received four doses. Echocardiographic
      assessments of ventricular function were made before and 3-5 days after
      Levosimendan infusion. MEASUREMENTS AND MAIN RESULTS: Heart rate, systolic
      pressure, diastolic pressure, mean blood pressure, and central venous pressure
      were unchanged during and after Levosimendan. Levosimendan allowed for
      discontinuation of catecholamines in ten patients and a dose reduction in three.
      The dose of dobutamine was reduced from 6.4 microg/kg/min pre-Levosimendan to 1.8
      microg/kg/min on day 5 (p < .01). Ejection fraction for the group as a whole
      improved from 29.8% to 40.5% (p = .015); this did not increase significantly in
      patients with end-stage heart failure but increased by 63% in the children with
      acute heart failure. CONCLUSIONS: Levosimendan can be safely administered to
      infants and children with severe heart failure. Levosimendan allowed for
      substantial reduction in catecholamine infusions in children with end-stage or
      acute heart failure and also produced an objective improvement in myocardial
      performance in children with acute heart failure.

PMID- 16885789
TI  - Combining lung-protective strategies in experimental acute lung injury: The
      impact of high-frequency partial liquid ventilation.
AB  - OBJECTIVE: To evaluate the independent and combined effects of high-frequency
      oscillatory ventilation (HFOV) and partial liquid ventilation (PLV) on gas
      exchange, pulmonary histopathology, inflammation, and oxidative tissue damage in
      an animal model of acute lung injury. DESIGN: Prospective, randomized animal
      study. SETTING: Research laboratory of a health sciences university. SUBJECTS:
      Fifty New Zealand White rabbits. INTERVENTIONS: Juvenile rabbits injured by
      lipopolysaccharide infusion and saline lung lavage were assigned to conventional
      ventilation (CMV), PLV, HFOV, or high-frequency partial liquid ventilation (HF
      PLV) with a full or half dose (HF-PLV1/2) of perfluorochemical (PFC). Uninjured
      ventilated animals served as controls. Arterial blood gases were obtained every
      30 mins during the 4-hr study. Histopathologic evaluation was performed using a
      lung injury scoring system. Oxidative lung injury was assessed by measuring
      malondialdehyde and 4-hydroxynonenal in lung homogenates. MEASUREMENTS AND MAIN
      RESULTS: HFOV, PLV, or a combination of both methods (HF-PLV) resulted in
      significantly improved oxygenation, more favorable lung histopathology, reduced
      neutrophil infiltration, and attenuated oxidative damage compared with CMV. HF
      PLV with a full PFC dose did not provide any additional benefit compared with
      HFOV alone. HF-PLV1/2 was associated with decreased pulmonary leukostasis
      compared with HF-PLV. CONCLUSIONS: The combination of HFOV and PLV (HF-PLV) does
      not provide any additional benefit compared with HFOV or PLV alone in a combined
      model of lung injury when lung recruitment and volume optimization can be
      achieved. The use of a lower PFC dose (HF-PLV1/2) is associated with decreased
      pulmonary leukostasis compared with HF-PLV and deserves further study.

PMID- 16885790
TI  - Near-infrared spectroscopy in the detection of regional tissue oxygenation during
      hypoxic events in preterm infants undergoing critical care.
AB  - OBJECTIVES: To determine whether pulse oximetry-detected episodes of desaturation
      are associated with impairment of cerebral and somatic (renal) tissue oxygenation
      in mechanically ventilated preterm neonates. DESIGN: Observational cross
      sectional study. SETTING: Neonatal intensive care unit of a university-affiliated
      children's hospital. PATIENTS: Ten mechanically ventilated preterm (gestational
      age 24-32 wks) infants. INTERVENTIONS: In addition to the traditional monitoring
      of hemodynamic variables that included pulse oximetry (Sao2), near-infrared
      spectroscopy (NIRS) was used to evaluate the cerebral and somatic (renal) tissue
      oxygen saturation (rSO2C and rSO2R, respectively). MEASUREMENTS AND MAIN RESULTS:
      A total of 40 rSO2C and rSO2R measurements were simultaneously recorded: 20
      during hypoxic events when the Sao2 was </=80% for >/=4 secs (cases) and
      generally ranged between 70% and 80%, and 20 measurements when the Sao2 was
      >/=85% (paired controls). Additionally, the fractional oxygen extraction (FOE)
      from the cerebral (FOEC) and renal (FOER) tissue was calculated. All the
      measurements were made under steady conditions during a 2-hr period. The rSO2C,
      rSO2R, FOEC, and FOER among the cases (Sao2 </= 80%) and controls (Sao2 >/= 85%)
      were compared using the paired Student's t-test. Both rSO2C and rSO2R during the
      desaturation episodes were lower than in the controls (51.6 +/- 6.3% vs. 66.2 +/-
      10.2%, p < .0001 and 61.1 +/- 6.8% vs. 80.1 +/- 10.0%, p < .0001, respectively).
      The FOEC during the hypoxic episodes was comparable with control levels but
      increased in renal tissue. However, during two of the desaturation episodes
      (10%), the rSO2C and FOEC levels (which were <44% and >0.47, respectively) may
      reflect compromised tissue oxygen supply. CONCLUSIONS: In the majority of
      mechanically ventilated preterm neonates, the reduction in cerebral and renal
      tissue oxygenation associated with short periods of decreased arterial saturation
      to 70-80% does not significantly compromise oxygen utilization in the cerebral
      tissue but increases oxygen extraction in the renal tissue, which might cause
      ischemic tissue injury following a further reduction in oxygen delivery.

PMID- 16885791
TI  - A child with anterior mediastinal mass supported with veno-arterial
      extracorporeal membrane oxygenation.
AB  - OBJECTIVE: To demonstrate the utility of rescue with veno-arterial extracorporeal
      membrane oxygenation (VA-ECMO) and to demonstrate the feasibility of
      administration of chemotherapy during VA-ECMO in a child with an anterior
      mediastinal mass. DESIGN: Case report. SETTING: Large, tertiary care, pediatric
      intensive care unit. PATIENT: One patient with cardiopulmonary collapse in the
      setting of a new diagnosis of an anterior mediastinal mass. INTERVENTIONS:
      Cardiopulmonary support with VA-ECMO; administration of chemotherapy during VA
      ECMO. MEASUREMENTS AND MAIN RESULTS: Successful rescue with VA-ECMO and
      successful chemotherapy while on VA-ECMO. CONCLUSIONS: VA-ECMO can be
      successfully used to support patients with cardiopulmonary failure during initial
      diagnosis of an anterior mediastinal mass. In addition, we have demonstrated that
      successful chemotherapy can be administered while the patient is supported on VA
      ECMO.

PMID- 16885792
TI  - Prone positioning can be safely performed in critically ill infants and children.
AB  - OBJECTIVE: To describe the effects of prone positioning on airway management,
      mechanical ventilation, enteral nutrition, pain and sedation management, and
      staff utilization in infants and children with acute lung injury. DESIGN:
      Secondary analysis of data collected in a multiple-center, randomized, controlled
      clinical trial of supine vs. prone positioning. SETTING: Seven pediatric
      intensive care units located in the United States. PATIENTS: One hundred and two
      pediatric patients (51 prone and 51 supine) with acute lung injury.
      INTERVENTIONS: Patients randomized to the supine group remained supine. Patients
      randomized to the prone group were positioned prone per protocol during the acute
      phase of their illness for a maximum of 7 days. Both groups were managed using
      ventilator and sedation protocols and nutrition and skin care guidelines.
      MEASUREMENTS AND MAIN RESULTS: Airway management and mechanical ventilatory
      variables before and after repositioning, enteral nutrition management, pain and
      sedation management, staff utilization, and adverse event data were collected for
      up to 28 days after enrollment. There were a total of 202 supine-prone-supine
      cycles. There were no differences in the incidence of endotracheal tube leak
      between the two groups (p = .30). Per protocol, 95% of patients remained
      connected to the ventilator during repositioning. The inadvertent extubation rate
      was 0.85 for the prone group and 1.03 for the supine group per 100 ventilator
      days (p = 1.00). There were no significant differences in the initiation of
      trophic (p = .24), advancing (p = .82), or full enteral feeds (p = .80) between
      the prone and supine groups; in the average pain (p = .81) and sedation (p = .18)
      scores during the acute phase; and in the amount of comfort medications received
      between the two groups (p = .91). There were no critical events during a turn
      procedure. While prone, two patients experienced an obstructed endotracheal tube.
      One patient, supported on high-frequency oscillatory ventilation, experienced
      persistent hypercapnea when prone and was withdrawn from the study. The
      occurrence of pressure ulcers was similar between the two groups (p = .71).
      Compared with the supine group, more staff (p </= .001) and more time were
      necessary to reposition patients in the prone group. CONCLUSIONS: Our data show
      that prone positioning can be safely performed in critically ill pediatric
      patients and that these patients can be safely managed while in the prone
      position for prolonged periods of time.

PMID- 16885793
TI  - Continuous positive airway pressure with modified helmet for treatment of
      hypoxemic acute respiratory failure in infants and a preschool population: a
      feasibility study.
AB  - OBJECTIVE: To analyze the feasibility of using continuous positive airway
      pressure (CPAP) delivered via a modified helmet to treat children with hypoxemic
      acute respiratory failure. DESIGN: A single-center, prospective, clinical study.
      SETTING: Pediatric intensive care unit in a university hospital. PATIENTS:
      Fifteen consecutive children (from 1 month to 5 yrs of age) with hypoxemic acute
      respiratory failure (defined as Pao2/Fio2 <300). INTERVENTIONS: CPAP was
      delivered via a modified helmet (CaStar, Starmed, Italy) of reduced size,
      fastened by a device we call a "baby-body." The feasibility of CPAP with the
      helmet was the primary end point. The improvement of gas exchange was the
      secondary one. MEASUREMENTS AND MAIN RESULTS: Ten of 15 children had multiple
      organ failure. Nine of 15 children were </=1 yr old. The helmet was well
      tolerated by all the children. Additional sedation was provided to four patients.
      No children developed significant complications (skin lesion, gastric distension,
      conjunctivitis, epistaxis, or loss of invasive devices) or lethal, helmet-related
      events. Oxygenation improved above baseline after 2 hrs of CPAP with the helmet;
      no significant variation of hemodynamic variables was detected. CONCLUSIONS: The
      helmet is a suitable device for delivery of CPAP to infants and preschool
      children with hypoxemic acute respiratory failure. It was well tolerated and
      improved oxygenation.

PMID- 16885794
TI  - Total phenytoin concentrations do not accurately predict free phenytoin
      concentrations in critically ill children.
AB  - OBJECTIVE: To determine the relationship between estimated free, measured free,
      and measured total phenytoin levels in critically ill pediatric patients, assess
      the utility of the Sheiner-Tozer equation in predicting free phenytoin levels,
      and identify comedications that may influence phenytoin binding or confound
      attempts to maintain therapeutic concentrations. DESIGN: Retrospective chart
      review. SETTING: Twenty-four-bed medical-surgical pediatric intensive care unit.
      PATIENTS: Sixty critically ill pediatric patients receiving phenytoin for
      treatment of seizures in a large multidisciplinary intensive care unit.
      INTERVENTIONS AND MAIN RESULTS: The linear correlation between free and total
      phenytoin concentrations was moderate (r = .795), but the mean difference between
      actual free concentrations and those estimated from total concentrations using
      the Sheiner-Tozer equation was -0.31 +/- 0.5 microg/mL (95% confidence interval, 
      1.3 to 0.7). This difference was of concern, as 10% of patients had toxic free
      levels (>2 microg/mL) when simultaneously measured total levels were therapeutic
      (<20 microg/mL). The mean free/total phenytoin ratio was 0.13 +/- 0.07 (range,
      0.06-0.42) and varied considerably among patients. Free fractions were
      particularly elevated in children whose serum albumin concentrations were <2.5
      g/dL (0.22, p < .001). However, the relationship between free phenytoin and serum
      albumin concentration appeared to be nonlinear. Coadministration of valproic acid
      and cefazolin also increased free fraction (p < .001). CONCLUSIONS: Measured
      total phenytoin concentrations are unreliable for directing therapy in critically
      ill children. In part, this is because phenytoin binding shows greater
      variability in this population than has been reported in adults. This phenomenon
      is exacerbated by coadministration of other highly protein-bound drugs. Instead,
      free phenytoin concentrations should be routinely measured in critically ill
      children to prevent possible intoxications and ensure therapeutic dosing.
      Corrections using the Sheiner-Tozer equation were unreliable.

PMID- 16885795
TI  - Epidemiology and early predictive factors of mortality and outcome in children
      with traumatic severe brain injury: experience of a French pediatric trauma
      center.
AB  - OBJECTIVE: To describe the results of an integrated pre- and in-hospital approach
      to critical care in a large population of children with severe traumatic brain
      injury and to identify the early predictors of their outcome. DESIGN: A 9-yr
      retrospective review of the data of a trauma data bank. SETTING: Level III
      pediatric trauma center. PATIENTS: All children (1 month to 15 yrs) with severe
      traumatic brain injury (Glasgow Coma Scale </=8) hospitalized in our trauma
      center and followed until death or for >/=6 months after discharge.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Univariate and further
      multivariate analyses were performed to determine independent predictive factors
      of death and outcome at discharge and 6 months later. The Glasgow Outcome Scale
      was used to evaluate outcome; a poor outcome referred to Glasgow Outcome Scale
      >/=3. Receiver operating characteristic curves were drawn to determine the
      threshold values of predictors of death and outcome. Analysis concerned 585
      children (67% male and 33% female). Mean age was 7 +/- 5 yrs. Predominant
      mechanisms of injury were road traffic accidents and falls. Mean values for
      Glasgow Coma Scale, Pediatric Trauma Score, and Injury Severity Score were 6 (3
      8), 3 (-4,10), and 28 (4-75), respectively. Mortality rate was 22%; Glasgow
      Outcome Scale was <3 in 53% of the cases at discharge and 60% at 6 months.
      Multivariate analysis identified Glasgow Coma Scale, Injury Severity Score, and
      hypotension on arrival as independent predictors of death and poor outcome at
      discharge and at 6 months. Threshold values for death were 28 for Injury Severity
      Score and 5 for Glasgow Coma Scale. The same values were found for poor outcome,
      except for outcome at 6 months where threshold value for the Glasgow Coma Scale
      was 6. CONCLUSIONS: Initial hypotension, Glasgow Coma Scale, and Injury Severity
      Score are independent predictors of outcome in children with traumatic brain
      injury. Threshold values can be calculated for predicting poor outcome. These
      variables can be easily and detected early in this population and used for
      quality assessment.

PMID- 16885796
TI  - Considering the use of induced hypothermia in a pediatric patient with traumatic
      brain injury: a critical appraisal of two meta-analyses.
AB  - OBJECTIVE: To review whether induced hypothermia after traumatic brain injury
      affects morbidity and mortality based on the results of two meta-analyses.
      DESIGN: Critical appraisals of McIntyre et al: Prolonged therapeutic hypothermia
      after traumatic brain injury in adults: A systematic review. JAMA 2003; 289:2992
      2999, and Henderson et al: Hypothermia in the management of traumatic brain
      injury: A systematic review and meta-analysis. Intensive Care Med 2003; 29:1637
      1644. FINDINGS: Both meta-analyses included trials of adult patients with severe
      traumatic brain injury randomized to induced hypothermia or normothermia and
      evaluated risk of death and poor neurologic outcomes. McIntyre et al. found the
      overall relative risk of mortality with induced hypothermia to be 0.81 (95%
      confidence interval 0.69-0.96). By designing a priori analyses, these authors
      also found that the relative risk of death was reduced in patients cooled for >48
      hrs, and the risk of poor neurologic outcome was reduced with all durations of
      cooling, cooling to 32-33 degrees C, and rewarming in <24 hrs. In contrast,
      Henderson et al. found that induced hypothermia did not change the odds of death
      after traumatic brain injury (odds ratio 0.81; 95% confidence interval 0.59-1.13)
      and that normothermic controls had an odds ratio of 0.42 (95% confidence interval
      0.25-0.70) for developing intercurrent pneumonia. Both analyses found trials to
      be heterogeneous with respect to neurologic outcome. CONCLUSIONS: The
      discrepancies in the results of these contemporaneous meta-analyses may stem, in
      part, from differences in their trial selection strategies as well as from
      sources of trial heterogeneity. Nevertheless, McIntyre et al. uncovered the
      equivalent of a dose-dependent reduction in the risk of death with induced
      hypothermia, supporting further study of this neuroprotective strategy. Although
      these meta-analyses included trials containing adult patients, a phase II trial
      of induced hypothermia in pediatric traumatic brain injury has established its
      feasibility and safety in infants and children. As in adult patients, induced
      hypothermia for traumatic brain injury in children can be considered an optional
      therapy for refractory intracranial hypertension but should not be regarded as
      standard of care.

PMID- 16885797
TI  - Physician experience with family presence during cardiopulmonary resuscitation in
      children.
AB  - OBJECTIVE: Family presence during cardiopulmonary resuscitation in children is an
      emerging practice. Although many hospitals allow this practice, there is scant
      research on physician attitudes and opinions and on physician views about
      training for resident physicians. DESIGN: Survey method. SETTING: University and
      community settings. PATIENTS: We randomly selected 1,200 pediatric critical care
      and emergency medicine providers from professional association mailing lists.
      INTERVENTION: The providers were mailed up to two written surveys and two
      reminder cards. The survey consisted of 40 multiple-choice and short-answer
      questions about demographics, past experiences, and opinions on pediatric family
      presence. MEASUREMENTS AND RESULTS: Of 1,200 surveys mailed, 521 were completed
      (43.4%) and 73 (6.1%) respondents returned the form declining to participate.
      More than 99% of respondents were physicians. Four hundred and thirty-three
      respondents (83%) reported participation in pediatric resuscitation with family
      members present, with a mean of 15 episodes ever and three episodes within the
      last year. Of those who had ever participated, more than half thought it was
      helpful for the family, and two thirds believed that parents wanted the option.
      Ninety-three percent would allow family presence in some situations. Seventy-four
      percent believed family presence would be stressful for a resident physician, but
      nearly 80% believed that residents working with children should be educated in
      this area. CONCLUSIONS: Family presence during cardiopulmonary resuscitation in
      children is not an uncommon experience for health care providers. Most
      respondents had resuscitated a child with family members present. The majority
      thought that presence was helpful to parents and that residents should be trained
      in this practice.

PMID- 16885799
TI  - [Autosomal dominant syndrome of retinal arterial tortuosity].
AB  - INTRODUCTION: Autosomal dominant syndrome of retinal arterial tortuosity is a
      rare condition, often discovered after a benign macular hemorrhage. CASE REPORT:
      We report here the case of a 52-year-old man who was refereed to our center for
      an abrupt decrease in vision after an effort. The initial visual acuity was 2/10
      for distance and Parinaud 6 for near vision. The biomicroscopic examination
      showed a small foveal hemorrhage associated with loops and bilateral vascular
      tortuosities limited to the arterioles. The aspect evoked inherited retinal
      arteriolar tortuosity. Questioning the patient revealed an antecedent of macular
      hemorrhage in the patient's sister that had spontaneously resolved. After a few
      months, redfree photographs were obtained from the two asymptomatic daughters of
      the patient, which showed a dominant arterial tortuosity in one of the two
      daughters, confirming the familial aspect of the disease. CONCLUSION: The case
      described here illustrates the advantage of biomicroscopy in establishing the
      diagnosis and the usefulness of questioning the patient further to disclose
      family history. Imagery studies complement the examination to eliminate other
      causes for the decrease in vision. Some recently published data suggest an
      advantage to including at least the search for a microscopic or macroscopic
      hematuria during the assessment.

PMID- 16885798
TI  - [Congenital anophthalmias: a case of trisomy 13].
AB  - Congenital anophthalmia is the result of a lack of development or regression of
      the primary optic vesicle in utero. It can be isolated or associated with other
      malformations and can be unilateral or, rarely, bilateral. Different etiologies
      are usually found such as chromosomal aberrations, gene mutations, toxic agents,
      and infections. We report a case of bilateral congenital anophthalmia in a
      setting of a polymalformative syndrome with microcephalia and bilateral lip
      cleft. Karyotype studies confirmed trisomy 13 known as Patau's syndrome. Trisomy
      13 is a rare lethal chromosomal aberration frequently responsible for uni- or
      bilateral microphthalmia and occasionally for anophthalmia.

PMID- 16885800
TI  - [Bilateral posterior microphthalmos associated with papillomacular fold and
      severe hyperopia].
AB  - Posterior microphthalmos with papillomacular fold is a rare disorder that
      involves both eyes without other ocular or systemic abnormalities. It is
      characterized by a short posterior segment with a normal anterior segment. We
      report the case of a 3.5-year-old boy with high hyperopia. The fundus examination
      showed bilateral papillomacular fold and ultrasonography confirmed the posterior
      microphthalmos. We comment on clinical characteristics, pathogenicity, and
      inheritance modes of this rare congenital disorder.

PMID- 16885801
TI  - [Management of ocular hypertension and chronic open-angle glaucoma by French
      ophthalmologists: the role of target intraocular pressure].
AB  - PURPOSE: A low level of intraocular pressure (IOP) can reduce or even stop the
      progression of glaucoma. It is essential to limit conversion from ocular
      hypertension (OHT) to glaucoma. The IOP value that protects the visual field and
      the optic nerve is called target IOP. This study analyzes how French
      ophthalmologists determine the target IOP level. MATERIAL AND METHODS: The main
      objective of this prospective, multicenter national survey was to analyze the
      management of OHT or glaucoma patients and to evaluate the importance of target
      IOP in the therapeutic strategy. RESULTS: A total of 972 ophthalmologists
      included 11.177 patients from May 2002 to March 2004. In 68.7% of cases, the
      practitioner determined the target IOP level using the following methods: a
      target of 15 mmHg or 17 mmHg or a reduction of the IOP level in percentage (EGS
      guidelines). This mean target IOP ranged from 14.3 to 17.3 mmHg. DISCUSSION: The
      estimation of target IOP is used by the majority of French ophthalmologists.
      CONCLUSION: This study shows that the determination of target IOP is becoming
      increasingly important in the therapeutic decision and follow-up in the routine
      practice of French ophthalmologists.

PMID- 16885803
TI  - [Advantages of the autorefractometer and the Orbscan for measuring pupil
      diameter].
AB  - PURPOSE: We compared pupil size measurements obtained with the Orbscan and
      autorefractometer to the Colvard Infrared pupillometer in order to determine
      their respective clinical advantages. MATERIAL AND METHODS: We prospectively
      measured the pupil diameter in 94 eyes of 47 normal patients using the Colvard
      device, the Nikon NKR 8000 autorefractometer, and the Orbscan device. For each
      device, two successive measurements were taken to determine its reproducibility.
      We also studied the relationship with the contralateral eye (i.e., difference and
      correlation). The measurements obtained with the different devices in different
      light intensities were compared and studied using regression analysis. RESULTS:
      Pupil diameter measured using the Orbscan had the highest reproducibility (mean
      difference between the two successive measurements: 3.8% or 0.15mm) and showed
      the smallest difference between the two eyes (5.0% or 0.19mm) and the strongest
      correlation with the contralateral eye (r=0.93; p<0.001). Scotopic Colvard
      measurements and autorefractometer measurements with low light settings were not
      significantly different (5.86mm versus 5.86mm; p=0.48). Autorefractometer
      measurements with low light settings showed the strongest correlation with the
      scotopic Colvard measurements (r=0.84; p<0.001). The Orbscan measurements were
      less correlated with the scotopic or photopic Colvard measurements (r=0.73;
      p<0.001 and r=0.51; p=0.003, respectively). For the Colvard pupillometer, the
      correlation between photopic measurements and scotopic measurements was also poor
      (r=0.51; p<0.001). CONCLUSION: Pupil size measurements with the autorefractometer
      may be advantageous before refractive surgery. Measuring pupil size in photopic
      conditions, as with the Orbscan, cannot screen people with large pupils in
      mesopic conditions.

PMID- 16885802
TI  - [Deep lamellar keratoplasty versus penetrating keratoplasty for keratoconus].
AB  - OBJECTIVE: To determine the advantages, safety, and accuracy of deep anterior
      lamellar keratoplasty (DLK) versus penetrating keratoplasty (PK) in terms of
      visual acuity, astigmatism, and endothelial preservation in corneal diseases with
      healthy endothelium. Of these candidates for keratoplasty, the study investigated
      keratoconus patients with no other ophthalmic abnormalities. MATERIALS AND
      METHODS: This comparative nonrandomized retrospective study investigated 22
      patients with keratoconus requiring surgery, who underwent keratoplasty in the
      Nantes University Hospital between 1 June 2002 and 1 January 2004. Ten DLK, ten
      PK and two PK converted DLK cases were analyzed. Follow-up at 2 weeks and at 3,
      6, 9, and 18 months is reported for visual acuity, astigmatism, pachymetry,
      specular microscopy, and intraocular pressure (IOP). Data are compared before and
      after surgery at each follow-up date. RESULTS: Preoperative visual acuity
      improved in both groups from 0.14+/-0.13 to 0.8+/-0.17 postoperatively. There was
      no significant difference between the two groups before and at each time after
      surgery for visual acuity and astigmatism (3.5+/-2 diopters in the PK group and
      3+/-0.9 D in the DLK group). There was a statistical difference for IOP with two
      occurrences of increased IOP up to 30 mmHg in the PK group. Endothelial cell
      count analysis showed an immediate postoperative decrease of 10% in the DLK group
      (versus approximately 40% in the PK group), remaining rather stable the 1st year
      (-3.3%), although cell loss in the PK group declined up to 10% more at 18 months.
      DISCUSSION: With no statistical difference between the two groups for visual
      acuity and astigmatism, DLK is effective. It is safer than PK in terms of IOP
      disturbance (leading cause of graft failure) and endothelial cell loss. DLK
      converted into PK (16%) showed the same profile as first-intention PK.
      CONCLUSION: Despite very similar effectiveness, DLK in keratoconus surgery should
      be proposed rather than PK because it appears safer not only in the short term
      but also probably in the long term, with no risk of endothelial cell rejection.

PMID- 16885804
TI  - [Three-dimensional computer-assisted modeling of the orbital cavity and the
      eyelids].
AB  - PURPOSE: To develop a virtual model of the orbital cavity and the eyelids using a
      three-dimensional model. METHODS: Amapi Designer 7 and Carrara 3 Studio (Eovia,
      Mountain View, CA, USA) software were used to obtain 3D models of the orbital
      cavity and the eyelids. Three-dimensional creation is divided into two main
      processes. In the modeling process, a 3D model of the orbit, the arterial supply,
      and the eyelids are created using polygonal meshes and surgical tools with
      parametric surfaces. In the rendering process, colors are arbitrarily chosen to
      make elements in the model easier to read. A virtual camera is adjusted and light
      sources are created to produce virtual simulations of the orbit and the eyelids.
      RESULTS: Surgical techniques were illustrated with 3D models. Ptosis surgery
      (resection of the levator muscle and Muller's muscle conjunctival resection) and
      the transconjunctival approach to lower eyelid blepharoplasty were described step
      by step. CONCLUSION: Three-dimensional models have applications in many medical
      fields, providing representation of anatomical structures. They can be used to
      depict the anatomy of the orbital region in a realistic way. Three-dimensional
      computer-generated images are an aid in teaching residents in orbital anatomy and
      surgery.

PMID- 16885805
TI  - [Interferon and retinal vasculitis].
AB  - The treatment of noninfectious posterior uveitis can lead to severe vision loss,
      and the first-line conventional treatment includes systemic steroids. When the
      prednisone doses necessary to control intraocular inflammation are above
      0.3mg/day, a therapeutic association is proposed in order to lower the daily
      prednisone dose. The combined drugs are immunosuppressive or immunomodulative.
      The side effects of immunosuppressive drugs are oncogenic, infectious, and
      hematological, and can involve reproductive troubles, associated with specific
      toxic effects depending on the drug used. Recently adding polyclonal or
      monoclonal antibodies and the interferons to immunomodulative drugs has been
      suggested. Interferon alpha has been shown to be effective in Behcet's disease.
      The efficacy of interferon needs to be evaluated in other etiologies of retinal
      vasculitis through randomized studies.

PMID- 16885806
TI  - [Intraocular fluids analysis for etiologic diagnosis of presumed infectious
      uveitis].
AB  - PURPOSE: To study the etiologic distribution of patients with presumed infectious
      uveitis who underwent ocular fluid analysis. PATIENTS AND METHODS: We
      retrospectively analyzed vitreous and or aqueous humor samples of patients with
      presumed infectious uveitis, referred to the department of Ophthalmology of the
      University Hospital of Rouen, France, between January 1997 and June 2004. We
      excluded patients with postsurgical or endogenous endophthalmitis. We noted
      clinical features and intraocular sample analysis methods for each pathogen.
      RESULTS: The study included 42 patients, 24 men and 18 women, aged between 6 and
      79 years (mean, 39.5 years). Uveitis was unilateral in 88% of cases and bilateral
      in 12%. Posterior uveitis was predominant (52%), followed by panuveitis (24%),
      anterior (14%), and intermediate uveitis (10%). Aqueous humor and vitreous
      analysis confirmed etiological diagnosis for 13 of 41 patients (31%) and three of
      six cases (50%), respectively. Inflammation was controlled or stabilized in all
      cases. The most pejorative visual outcome was observed for candidiasis and viral
      retinitis. Positivity of intraocular samples was variable, depending on the
      suspected pathogen, with results similar to those reported in other studies.
      DISCUSSION: Atypical features in potential infectious uveitis justify ocular
      paracentesis or vitrectomy, which are more efficient since molecular biological
      tools have become available. Sensitivity of aqueous humor analysis is high for
      posterior uveitis and suspicion of viral retinitis. New molecular variants
      applied to ocular samples will improve the etiological diagnosis of infectious
      uveitis, particularly for pathogens that are difficult to culture, such as fungi
      and bacteria.

PMID- 16885807
TI  - [Study of pupillary motility after implantation of an iris claw lens (Artisan) in
      a phakic population with severe myopia].
AB  - PURPOSE: To assess the effect of the Artisan lens on pupillary motility in a
      highly phakic myopic population. PATIENTS AND METHODS: Eleven patients (21 eyes)
      were enrolled in a nonrandomized prospective study between September 2002 and
      August 2003, with a 6- to 11-month follow-up. A portable Colvard pupillometer was
      used to measure pupil diameters before and after surgery under two different
      light conditions: one with scotopic surroundings with absolute darkness in the
      examination room and the other maximal simulated photopic surroundings, caused by
      the instillation of a pilocarpine 2% drug until a nonreactive myosis could be
      observed. Under such light conditions, both the horizontal and vertical pupil
      motion ranges were measured. Measures were then sorted into five temporal
      segments in order to have enough samples per temporal segment for a cohesive data
      analysis. Mean values and confidence intervals were then derived per temporal
      segment according to Student's law. Constraints on the pupil motion range were
      identified. RESULTS: After implantation of an Artisan lens, the pupil motion
      range was limited to both horizontal and vertical axes. For the horizontal axis,
      the motion range was 4.3+/-0.2mm (p=0.1) before claw implantation and was 2.7+/
      0.5mm (p=0.1) 9 months after claw implantation. For the vertical axis, the motion
      range was 4.46+/-0.28mm before claw implantation and 3.08+/-0.89mm 9 months after
      claw implantation. CONCLUSIONS: The Artisan lens durably restrains the pupil in
      its motion range and introduces a noticeable oval deformation under extreme light
      condition variations. This side effect is, however, not visible under regular
      conditions but only in maximal photopic surroundings.

PMID- 16885808
TI  - [Treatment of a subretinal silicone oil bubble].
AB  - The passage of a silicone oil bubble under the retina is a rare but severe
      complication of retinal detachment (RD) surgery. It may cause a permanent
      detachment and/or migrate with time, decreasing visual function. We present five
      cases in which the subretinal oil bubble was successfully extracted from the
      subretinal space by retinotomy. Two cases were rhegmatogenous RD with
      proliferative vitreoretinopathy, two were post-traumatic RD, and one was a
      traction detachment in proliferative diabetic retinopathy. The average follow-up
      was 17 months. In three cases, we were able to remove the silicone oil from the
      eye. In all cases, visual acuity was improved. Using retinotomy to extract the
      subretinal oil bubble seems a safe way to manage this complication.

PMID- 16885809
TI  - [Iris mammillations: three case reports].
AB  - INTRODUCTION: Iris mammillations are congenital abnormalities characterized by
      vitiliform protuberances regularly spaced on the surface of a velvety iris. They
      can be either isolated or associated with melanocytosis involving iris, sclera or
      periocular tissues, resulting in a risk for uveal melanoma. They can be
      complicated by ocular hypertension. We report three cases of iris mammillations
      in three children. CASES REPORT: For each patient, age, circumstances of
      revelation, anterior and posterior segment examination, intraocular pressure,
      associated anomalies, and progression were noted. Patient no. 1: In a 13-month
      old boy examined for a squint, bilateral iris mammillations were fortuitously
      discovered. Intraocular pressure remained normal over 22 months of follow-up.
      Patient no. 2: In an eight-year-old boy, bilateral iris mammillations with
      papillary excavation were fortuitously discovered. Intraocular pressure was
      normal and the excavation did not change over 20 months of follow-up. Patient no.
      3: A five-year-old boy was examined for a scleral pigmentation in the right eye.
      The examination found unilateral iris mammillations and ipsilateral ocular
      melanocytosis. Intraocular pressure and fundus were normal and remained normal
      over 13 months of follow-up. DISCUSSION: and conclusion: Iris mammillations are
      congenital abnormalities, generally unilateral, sometimes hereditary. The
      differential diagnosis includes Lisch nodules of neurofibromatosis and iris
      melanoma. The etiology of iris mammillations is unknown; these lesions can be
      complicated by ocular hypertony and, in case of associated melanocytosis of the
      iris, sclera or periocular tissues, by uveal melanoma. These potential
      complications warrant a regular clinical follow-up.

PMID- 16885811
TI  - [Ondine's Curse and rare oculomotor abnormalities: a case report].
AB  - Ondine's Curse or congenital central hypoventilation syndrome (CCHS) is a
      neurocristopathy (failure of migration or differentiation of neural crest-derived
      precursor cells) and is characterized by hypoventilation or apnea, which is most
      pronounced during sleep, with no other abnormalities of the neuro-respiratory
      system. Because of respiratory distress soon after birth, patients must be
      intubated and ventilated for a long time. This disorder may be associated with
      other symptoms of neurocristopathy (Hirschsprung disease, neuroblastoma,
      neuroganglioma) and other abnormalities of the autonomic nervous system
      (vasomotor dysfunctions or ophthalmic abnormalities: abnormal pupils,
      insufficient convergence, strabismus, or ptosis). We report the original case of
      a CCHS patient who presented with alternative ptosis of both the right and left
      eyes and esotropia. The ocular findings should lead to earlier diagnosis and
      speedier adequate treatment.

PMID- 16885810
TI  - [Allgrove syndrome. Report on a family].
AB  - Triple A or Allgrove syndrome is a rare autosomal recessive disease with
      alacrima, achalasia, and ACTH-resistant adrenal insufficiency. It is usually
      associated with neurological disorders. Recently, mutations in the AAAS, a
      candidate gene mapped to chromosome 12q13, were identified. We report a family
      with seven affected siblings. All of them have signs of alacrima, four were
      operated on for achalasia, five have neurological abnormalities including cranial
      nerve abnormalities, amyotrophic lateral sclerosis, pyramidal syndrome, distal
      motor neuropathy, and amyotrophy, and two have adrenal insufficiency. Triple A
      syndrome should be considered in any young patient with alacrima.

PMID- 16885813
TI  - [Convergence excess associated with neurological diseases: surgical treatment].
AB  - BACKGROUND: Lesions of the supranuclear pathways for convergence control can lead
      to convergence deficit or convergence excess. Whereas pathophysiology of acquired
      convergence excess is now fully covered in the literature, no specific paper on
      its surgical treatment could be found. PATIENTS: Cases 1 and 2: Parinaud's
      syndrome with convergence excess in attempted upgaze (+ convergence retraction
      nystagmus and VIth nerve palsy in case 2). Case 3: opsoclonus and convergence
      excess due to hysterical conversion after head trauma. Case 4: acquired
      nystagmus, accommodative spasm due to hyperopia. Case 5: functional spasm of the
      near reflex (dubious medical history of multiple sclerosis). Case 6: medial recti
      palsy after artificial divergence surgery for congenital nystagmus, substitutive
      convergence. Cases 3 and 5 were not operated on, recession of the four horizontal
      recti in case 4, recession of the lateral recti in case 6, complex surgical
      procedure in cases 1 and 2. DISCUSSION: The following guidelines are suggested:
      Functional spasm of the near reflex: medical therapy. Organic spasm of the near
      reflex: retroequatorial myopexia on the medial recti. Parinaud's syndrome with
      convergence excess (spastic) or convergence retraction nystagmus (rhythmic):
      restoration of upgaze motility with a vertical Kestenbaum-type procedure,
      retroequatorial myopexia if insufficient. Thalamic esotropia (tonic): botulinum
      toxin injection, recession of the medial recti if insufficient. CONCLUSION:
      Convergence excess associated with neurological diseases should be looked for
      since it can be improved by effective surgical procedures.

PMID- 16885812
TI  - [Optic nerve sheath meningioma: diagnosis and new treatment options, a case study
      of monocular blindness during pregnancy].
AB  - Optic nerve sheath meningiomas are challenging lesions to manage. We report here
      a case of primary optic nerve sheath meningioma in a pregnant woman with sudden
      unilateral vision loss. Then we review the current literature on the subject,
      prognosis factors, and report the results of fractionated radiotherapy and
      current therapeutic guidelines. Pregnancy may accelerate growth of meningiomas
      and this diagnosis must be considered in all cases of optic neuropathy in
      pregnant woman.

PMID- 16885814
TI  - [Risk calculator for developing glaucoma from ocular hypertension: beware of the
      risk of confusion].

PMID- 16885815
TI  - [Congenital cataract: general review].
AB  - Cataract is a loss of lens transparency because of a protein alteration.
      Etiopathogenesis is poorly understood but new mutations of different
      developmental genes involved are found in 25% of cases. Frequency of onset,
      particularly when different ocular development anomalies occur, is related to the
      lens induction phenomena on the eye's anterior segment structure during
      embryologic development. Genetic transmission is often found on the dominant
      autosomal mode. Diagnosis is based on a complete and detailed examination of the
      eye, often with general anaesthesia. This condition predisposes children to
      later, sometimes serious amblyopia. Different clinical aspects can be observed:
      from cataract with ocular and/or systemic anomalies to polymalformative syndrome,
      skeletal, dermatological, neurological, metabolic, and genetic or chromosomal
      diseases. A general systematic pediatric examination is necessary. Congenital
      cataract requires first and foremost early diagnosis and a search for all
      etiologies. Surgical treatment is adapted case by case but it has progressed with
      the quality of today's intraocular lenses even if systematic implantation
      continues to be debated. Life-long monitoring is absolutely necessary.

PMID- 16885816
TI  - [Etiopathogeny of intraocular pressure modifications in uveitis].
AB  - Uveitic glaucoma is a secondary form of glaucoma. Treatment is essentially
      medical, based on antiglaucomatous medications and immunomodulatory therapy.
      Therefore, some patients may need filtrating surgery to control intraocular
      pressure. Understanding the cellular and biochemical modifications of aqueous
      humor that occur during intraocular inflammation and identification of anatomical
      modifications of the iridocorneal angle, trabecula, pupil, and ciliary body allow
      physicians to adapt management depending on the different clinical patterns of
      uveitic glaucoma. We propose a general review of the role of inflammatory
      mediators and etiopathogenic mechanisms involved in uveitic glaucoma.

PMID- 16885817
TI  - [Central serous chorioretinopathy: visualizing leaks with OCT-3].

PMID- 16885818
TI  - [Reactivation of ocular toxoplasmosis after laser in situ keratomileusis].
AB  - Laser in situ keratomileusis (LASIK) is a safe and efficient refractive surgical
      procedure that provides excellent results in most cases. Several complications
      have been reported, most of them related to the posterior segment of the eye.
      Although they are quite rare, a growing number of vitreoretinal pathologic
      conditions after LASIK have been reported. To date no article has reported an
      inflammatory or infectious disease of the posterior segment after a LASIK
      procedure. We report a case of reactivation of toxoplasmic chorioretinitis that
      occurred 5 days after a LASIK procedure. Clinical outcome was spontaneously
      favorable after 1 month, with no loss of vision. Although a causal effect between
      LASIK and toxoplasmic chorioretinitis reactivation cannot be proven with a single
      case report, we stress the importance of dilated fundus examination in LASIK
      preoperative assessment: our case suggests that in the presence of preoperative
      toxoplasmic chorioretinitis scars, increased retinal monitoring is required.

PMID- 16885819
TI  - [Fundus albipunctatus incidentally discovered in a black African man].
AB  - Fundus albipunctatus is a recessive autosomal disease classified as one of the
      causes of congenital stationary night blindness. It is characterized by early
      hemeralopia beginning in infancy. We report the incidental discovery of the
      disease in a 23-year-old black African man with late hemeralopia onset. During
      the 4 years of follow-up, visual acuity, ERG, and visual field remained normal.
      We underline the possibility of late hemeralopia onset and discuss the possible
      progressive features of this disease. Progression may be conditioned by the
      mutation of the RDH5 gene, which codes for retinol dehydrogenase-5.

PMID- 16885821
TI  - [The Video Tearscope: a new method for evaluating lacrimal film in vivo].
AB  - PURPOSE: The lacrimal film has trophic, immunological, antimicrobial, and anti
      inflammatory roles. The lipidic phase of the tear film reduces surface stresses
      and limits tear evaporation. We present a reproducible and noninvasive
      investigation of the lacrimal film, the Video Tearscope (Vi-Te), which analyzes
      the after-blinking tear stabilization time and the different types of blinking.
      Vi-Te consists of a numerical video recording of the specular reflexion produced
      by the Tearscope Plus adapted to a biomicroscope. MATERIALS AND METHODS: Twenty
      four normal subjects and ten patients with dry eye syndrome were included. We
      studied the blinking types and LFST using the Vi-Te technique. The analysis was
      carried out at 25 images/s, corresponding to an in-between image interval of 40
      ms. RESULTS: Four types of spontaneous blinking were observed: complete, subtotal
      (99%-70% occlusion), partial (69%-20%), and abortive (less than 20%). We obtained
      a LFST value of 0.65+/-0.12s for the control group versus 2.34+/-1.28 s for the
      dry eye syndrome group. The difference was significant between the two groups for
      the LFST (p<0.001) for complete blinking. CONCLUSIONS: The Video Tearscope is a
      promising technique that provides new insights into tear film stability and
      physiology. The main weakness of this technique, however, is the time required
      for video analysis (20-45 min per case). Despite this drawback, additional
      studies should be undertaken in order to establish standards for evaluating
      ocular surface disorders in a completely noninvasive way.

PMID- 16885822
TI  - [Recessed inferior rectus syndrome: surgical exploration and pathophysiology].
AB  - INTRODUCTION: Progressive overcorrection after inferior rectus recession may
      occur in 10%-40% of cases, whatever the surgical indication, whatever the
      technique. The clinical features are hypertropia, inferior rectus underaction,
      and lid retraction. MATERIAL AND METHODS: The anatomy of the inferior rectus
      during surgical exploration is described in 11 cases initially operated on for
      different types of strabismus. RESULTS: Several types of slippage and several
      types of excessive fibrosis in the area of the inferior rectus are described.
      DISCUSSION: Our surgical data are compared to the pathophysiological hypothesis
      described in the literature. Preventive measures and curative treatment are
      discussed. CONCLUSION: Even a better understanding of the physiopathogenesis of
      overcorrection after inferior rectus recession could not prevent its occurrence,
      despite upgraded surgical technique. There is no consensual opinion on how to
      prevent and cure these overcorrections. Associating oculomotor surgery and lid
      surgery is an interesting direction for new research.

PMID- 16885823
TI  - [Inferior rhegmatogenous retinal detachments: clinical and therapeutic
      characteristics].
AB  - PURPOSE: To determine the epidemiological and clinical factors involved in
      inferior rhegmatogenous retinal detachments and to propose a therapeutic plan.
      PATIENTS AND METHODS: A retrospective case note review of 173 patients (175
      eyes), 11-89 years old, who had been operated on for inferior retinal detachment
      over a 13-year period between 1990 and 2003. RESULTS: The retinal reattachment
      rate after initial surgery was 79.5%, the final anatomical success rate was
      81.5%. Scleral buckling surgery was used for the primary repair of rhegmatogenous
      retinal detachments in 111 cases and it was successful in 81 cases. Fifty-eight
      patients underwent vitrectomy with internal silicone oil tamponade. Anatomical
      success was obtained in 55 cases (94.8%) without recurrence. Endocular surgery
      allowed surgeons to find missed causal tear in 76% of cases. Mixed surgery was
      undertaken in four cases, with three good results. Visual acuity improved in 81%
      of cases, remained unchanged in 15% of cases, and deteriorated in 4% of cases.
      The mean final visual acuity ranged from 2.5 to 3/10, while it was only 1/20
      before surgery. The mean improvement in visual acuity was 2.5 lines. The mean
      follow-up in our study was 13+/-11 months. CONCLUSION: Inferior retinal
      detachment usually occurred in young myopic or old pseudophakic subjects. These
      patients are characterized by the absence of tears. Vitrectomy in primary repair
      with inferior retinal detachment improves their anatomical and functional
      prognosis.

PMID- 16885824
TI  - [Intraocular foreign bodies: a descriptive and prognostic study of 52 cases].
AB  - BACKGROUND: The aim of this study was to determine prognostic factors as well as
      anatomical and functional outcomes in patients undergoing surgical removal of an
      intraocular foreign body, according to the ocular findings at presentation and
      surgical management. MATERIALS AND METHODS: Retrospective (1993-2003) clinical
      study of 52 consecutive patients, with univariate analysis adjusting for the
      initial and final clinical examinations, for the surgical strategy and
      complications. RESULTS: Final best corrected visual acuity of 5/10 or more was
      obtained in 35 patients (67%) and of 1/10 or more in 44 patients (85%). The
      prognostic factors of a final visual acuity less than 5/10 identified were an
      initial visual acuity less than 5/10 (p<0.001), age over 40 years (p=0.015), a
      foreign body larger than 3 mm (p=0.0015), and multiple surgeries (p=0.015).
      CONCLUSION: Thanks to recent surgical progress, final visual outcomes were
      excellent in 67% of patients. The initial visual acuity, age, the length of the
      foreign, and the number of surgical interventions were significant predictor
      factors. However, the anatomical and functional prognosis of intraocular foreign
      bodies remains difficult to establish at the initial clinical examination.

PMID- 16885825
TI  - [Acute posterior multifocal placoid pigment epitheliopathy, serpiginous and
      multifocal choroiditis: etiological and therapeutic management].
AB  - PURPOSE: To highlight the importance of an extensive medical work-up in
      serpiginous and multifocal choroiditis, and acute posterior multifocal placoid
      pigment epitheliopathy before therapeutic management. PATIENTS AND METHODS:
      Records of patients referred to our department, between January 2000 and January
      2002, for the diagnostic and therapeutic management of choroiditis or acute
      posterior multifocal placoid pigment epitheliopathy were retrospectively
      reviewed. All patients had a complete ophthalmologic examination, fluorescein and
      infrared angiographies. An extensive work-up was performed in order to exclude an
      infectious etiology. RESULTS: Fourteen patients were included (six cases of
      serpiginous choroiditis, four cases of multifocal choroiditis, and four cases of
      APMPPE). The mean age was 42.1 years and the sex ratio was 9: 5. Six patients
      presented with a history of tuberculosis in the family or with a tuberculosis
      primary infection. Toxoplasmic retinochoroiditis was confirmed in one case by a
      positive PCR applied to the aqueous humor. In the serpiginous choroiditis group,
      two patients have been treated with antituberculous drugs, one of whom was
      initially resistant to immunosuppressive regimens. In the acute posterior
      multifocal placoid pigment epitheliopathy group, one patient was treated with
      antituberculous drugs and another received antibiotics. CONCLUSION: An infectious
      agent may be associated with this group of clinical presentations. All patients
      presenting with severe forms of ocular inflammation, who resist to
      corticosteroids or immunosuppressive regimens, must undergo an extensive
      infectious work-up in order to propose a specific treatment.

PMID- 16885826
TI  - [The French glaucoma and ocular hypertension 1-day study].
AB  - PURPOSE: The purpose of this study was to describe the distribution and
      characteristics (age, duration, type, treatment, etc.) of ocular hypertension and
      glaucoma in French ophthalmologic practices. METHODS: The French glaucoma and
      ocular hypertension 1-day study is a descriptive cross-sectional "1-day" type
      survey, conducted among all ophthalmologists of mainland France. They had to
      include all patients aged 18 years and over with ocular hypertension or glaucoma
      who were seen on November 25th 2003. The participation rate was 24.0% (1.173
      ophthalmologists). Among the 3.919 patients included, 3.896 subjects (99%) had
      usable data for the statistical analyses. RESULTS: The ophthalmologists reported
      treating 16 patients with ocular hypertension or glaucoma on average per week.
      Among the patients, 29.5% had ocular hypertension, 61.7% had open-angle glaucoma,
      3.4% had normal tension glaucoma, and 5.5% angle-closure glaucoma. The
      ophthalmologists used surgery or laser treatment for 74.1% of angle-closure
      glaucoma, while for other pathologies, treatment with drugs only was
      preponderant. More than 87% of patients received one or several ocular
      treatments: beta-blockers (59.3%), prostaglandins (50.1%), carbonic anhydrase
      inhibitors (21.6%), or mydriatic sympathomimetics (6.3%). CONCLUSIONS: The
      characteristics of glaucoma and ocular hypertension (type of glaucoma, age,
      duration, etc.) correspond to those of other Western populations. The therapeutic
      habits of French ophthalmologists is in line with current international
      guidelines.

PMID- 16885827
TI  - [Ocular melanoma: immunohistochemical evaluation of the potentially predictive
      markers of prognosis. Preliminary results].
AB  - PURPOSE: To study the characteristics of certain biological parameters, many of
      which have been recently discovered, to assess their possible contribution to the
      prognosis of ocular melanoma. MATERIAL: and methods: 25 patients with ocular and
      orbital melanoma treated at the Reims Regional Hospital since 1993 were included
      in the retrospective study. The surgical specimens were put in formalin 10%, then
      in paraffin. Five proteins were analyzed retrospectively: topoisomerase I,
      topoisomerase IIalpha, ICBP90, Ki67, and P53 on 200 cells per case. RESULTS: Of
      the 25 tumors from 14 men and 11 women, 15 were iris and ciliary body melanomas
      and ten choroidal melanomas. Histopathologic analysis showed 12 spindle-cell-type
      melanomas, seven epithelioid-cell-type melanomas and six mixed-cell-type
      melanomas. The immunohistochemical study found a significant difference in
      distribution between the cellular types for the topoisomerase IIalpha and Ki67
      antibodies. Eight patients had metastasis, six of whom died. The metastasis came
      from three mixed-cell-type melanomas, three epithelioid-cell-type melanomas, and
      two spindle-cell-type melanomas. On the other hand, six cases of sclera
      infiltration were discovered among these eight patients. CONCLUSION: Several
      prognostic factors seem to be involved in the progression of melanoma: sclera
      infiltration seems to be essential in our study. Its rate seems to increase with
      the tumor size and in epithelioid-cell-type melanomas. The correlation between
      the different immunomarkers and the appearance of metastasis has not yet been
      verified.

PMID- 16885828
TI  - [Combined surgery for lens extraction, vitrectomy, and implantation in the
      diabetic patient using phacoemulsification versus phacofragmentation].
AB  - INTRODUCTION: In diabetic patients, we often need to perform cataract and pars
      plana vitrectomy. Two different techniques are currently valid: 1)
      phacoemulsification and pars plana vitrectomy and 2)pars plana lensectomy and
      posterior vitrectomy. METHODS: Retrospective study of two different groups of
      type 2 diabetic patients: those receiving 1) phacoemulsification and pars plana
      vitrectomy or 2) pars plana lensectomy and posterior vitrectomy. RESULTS: On
      statistical analysis there were no differences in complications between the two
      groups. The effect on visual acuity was similar in both groups. DISCUSSION: The
      association of cataract surgery and posterior vitrectomy is a valid technique for
      treating diabetic retinopathy complications. In the present study, the
      complications of the two techniques were similar, the most important concerning
      only anterior chamber opening in the first group. CONCLUSION: The two techniques
      of cataract extraction and pars plana vitrectomy at the same time have no
      differences in their results and are valid for treatment of diabetic patients.

PMID- 16885829
TI  - [GBR foldable anterior phakic intraocular lens with angular supports: a 3-year
      experience].
AB  - PURPOSE: The purpose of this study was to evaluate the efficiency,
      predictability, and safety of the GBR foldable anterior chamber implant with
      angular supports to correct high myopia after 3 years of follow-up. MATERIAL: and
      methods: A GBR anterior chamber lens with angular supports was implanted in 44
      eyes between November 2001 and February 2004. These eyes were highly myopic
      (preoperative mean of -10.65 +/- 2.62 diopters (D) (range, -6.25 to -16.50 D).
      Visual acuity, refraction, biomicroscopy, and quality of vision were estimated
      with a follow-up of 3 years. The potential complications required endothelial
      density, mobility of the pupil, intraocular pressure, and gonioscopy
      measurements. RESULTS: No severe intra- or postoperative complications required
      an ablation of the lens. Increased intraocular pressure in three cases and
      decentration in one were the most serious side effects reported. Eighteen eyes
      (40.9%) presented pupil ovalization; 68.2% of the eyes reached the attempted
      correction +/-0.50 D. Implants seemed stable in their position and refractive
      results. Functional signs included night glare for eight patients (18.2%) and
      glare in the sun for 11 (25%). There was no significant decrease in cellular
      endothelial density mean during follow-up. CONCLUSION: The GBR implant (Ioltech)
      is the pioneer of foldable anterior chamber implants, a concept in full
      expansion. Long-term satisfaction of the operated patients is encouraging.
      However, the medium-term anatomical modifications noted require monitoring and a
      search for the responsible mechanism.

PMID- 16885830
TI  - [Panuveitis following intravesical bacille Calmette-Guerin therapy].
AB  - Uveitis occurring after bacille Calmette-Guerin (BCG) intravesical therapy for
      bladder carcinoma is rare: only nine cases have been described. In two previous
      reports, vitreous cultures proved Mycobacterium bovis presence. We describe the
      case of an 85-year-old woman who presented with bilateral panuveitis 2 months
      after the last BCG intravesical instillation, with no other systemic symptom.
      There was no evidence for any other etiology for this uveitis. She was given oral
      antibiotics that were effective against Mycobacterium species, oral steroids, and
      anti-inflammatory drops. Her ophthalmologic status dramatically improved. This
      case highlights that these patients may have a good visual outcome, as long as
      diagnosis and treatment are not delayed.

PMID- 16885831
TI  - [Bilateral corneal endothelial decompensation after postsepticemia coma].
AB  - We report a case of unexplained bilateral corneal endothelial decompensation
      after a coma. A 71-year-old man with no medical history presented with bilateral
      endothelial decompensation that required penetrating keratoplasty of the left eye
      combined with cataract surgery. This coma was caused by septicemia originally due
      to staphylococcus infection following catheter placement in preparation for a CT
      scan. Visual acuity of the left eye was 20/400 and 20/100 in the right eye when
      the patient awoke from the coma. After examination, we noted only stromal
      thickening and Descemet membrane folds causing corneal edema predominating OS.
      The rest of the exam was normal. Six months after surgery, visual acuity improved
      to 20/25. The most probable physiopathological mechanism of this decompensation
      is an iatrogenic complication from drugs administered during the patient's stay
      in intensive care (oxacillin), but we cannot rule out direct aggression of a
      bacterium or its toxin or the decompensation of a preexisting pathology.

PMID- 16885833
TI  - [Advantages of the Cionni modified capsular tension ring with scleral fixation in
      large zonular dialysis].
AB  - INTRODUCTION: Large traumatic zonular dialysis (larger than 140) induces
      significant surgical problems. CASE REPORT: Two cases of large zonular dialysis
      with vitreous hernia in the anterior chamber, significant hypertonia, and
      cataract with subluxation of the lens are described. The surgical treatment
      consisted of ablation of the lens by phacoemulsification after anterior capsular
      rhexis and insertion of a conventional capsular tension ring. Then a Cionni ring
      was sutured to the sclera opposite the center of the zonular dialysis zone. The
      implant was inserted in the bag followed by an anterior vitrectomy. The IOL was
      centered in a stabilized bag in both patients. Postoperative visual acuity was
      excellent, with transitory hypertonia controlled with medical treatment.
      DISCUSSION: The conventional capsular tension ring does not allow effective
      treatment of large zonular dialysis or recentration of the bag. However, the
      Cionni modified ring stabilizes and recenters the bag, allowing capsular
      preservation and implantation in the bag. The authors describe the insertion
      technique for this type of ring. CONCLUSION: The Cionni ring seems to provide an
      effective surgical solution to large traumatic zonular dialysis with subluxation
      of the lens. However, the insertion technique for the ring is difficult to
      perform.

PMID- 16885832
TI  - [Cavitary choroidal melanoma in a child].
AB  - Uveal melanoma is very rare in children, and in both adults and children it can
      in rare cases develop intralesional cavities resembling an intraocular cyst. The
      presence of a solid mass at the base and a thick wall surrounding the cavity can
      assist in differentiating cavitary melanoma from a benign cyst. We report the
      case of a 5-year-old girl who presented with a large intraocular pigmented mass
      in the left eye, showing multiple hollow cavities on ocular ultrasonography, CT
      scan, and MRI. The patient was treated by enucleation and the pathology confirmed
      the diagnosis of choroidal melanoma. FISH revealed no aberration in chromosome 3.

PMID- 16885834
TI  - [Analogies between atherosclerosis and age-related maculopathy: expected roles of
      oxysterols].
AB  - The pathogenesis of age-related macular degeneration (ARMD) is not clearly
      understood. Like other age-related diseases, it is associated with abnormal
      deposits called drusen. These drusens are localized in Bruch's membrane. Recent
      investigations have shown a link between drusen formation and inflammatory and
      immunologic reactions. The involvement of oxidative stress is supported by
      available data as an important contributing factor in the developement of ARMD.
      The data regarding the nature and the source of the deposits suggest that ARMD
      may share similar pathways with atherosclerosis. The role of oxydized products of
      cholesterol, the oxysterols, in the pathogenesis of atherosclerosis is well
      known. As cholesterol is a constituent of drusens, oxysterols could be involved
      in retinal pigment epithelium and photoreceptor lesions occurring in ARMD owing
      to their cytotoxic, pro-inflammatory, and pro-oxydant properties.

PMID- 16885837
TI  - [Methotrexate in psoriasis: are routine biopsies necessary?].

PMID- 16885835
TI  - [Conjunctival biopsy: a useful procedure for the diagnosis of sarcoidosis].
AB  - PURPOSE: To highlight the advantages of conjunctival biopsy in order to confirm
      the diagnosis of sarcoidosis. CASE REPORT: A 78-year-old woman presented with
      unilateral vitreitis. The examination of the conjunctive of right and left eyes
      revealed multiple, translucent, pale yellow nodules the size of millet grains
      located in the lower fornix. The diagnosis of sarcoidosis was suspected by an
      increased level of angiotensin-converting enzyme and bilateral hilar
      lymphadenopathies. A biopsy from conjunctival nodules showed noncaseating
      epithelioid and gigantocellular granulomas, confirming the diagnosis of
      sarcoidosis. CONCLUSION: Although underused, conjunctival biopsy seems to be both
      a safe and effective tool in the diagnosis of sarcoidosis.

PMID- 16885838
TI  - [Outbreak of cutaneous dermatophytosis in the Judo French Programme in Orleans:
      September 2004-June 2005].
AB  - BACKGROUND: High contact sports regularly allow transmission of infectious
      agents, including fungi such as dermatophytes. The occurrence of dermatophytosis
      outbreaks among wrestlers has been extensively described since the 90s. The
      emergence of such outbreaks among judokas was described for the first time in
      December 2004. We report here an outbreak which occurred in a high level judo
      team and is, to our knowledge, the largest ever published. PATIENTS AND METHODS:
      From October 2004 to June 2005, every judokas of the Pole France Orleans who were
      suspect of dermatophytosis were addressed to one single dermatologist. Lesions
      were sampled for fungal culture and their anatomical cartography was extensively
      raised. Two protocols of treatment were defined. RESULTS: 97 medical appointments
      occurred over the period, leading to 74 clinically-defined episodes of
      dermatophytosis, distributed as 51 primo-contaminations and 23 re-contaminations
      (new episode in an individual who was considered cured). The distribution of the
      lesions on the body was: forearms > anterior trunk > neck and face > scalp. Among
      the 74 episodes, 53 could grow Trichophyton tonsurans. Infected athletes received
      oral and topical antifungal treatments. No adverse effects were noticed.
      DISCUSSION: This series among judokas is the largest ever published. It allowed
      the description of the specific clinical and anatomical presentation of tinea
      corporis gladiatorum, emphasising that contamination takes place through direct
      skin to skin contacts during practice. T. tonsurans is regularly the responsible
      fungus in recently published series. Caring for such an outbreak raises specific
      problems because of the numerous structures involved and of the nature of these
      structures and of the sportive goals they aim at. CONCLUSION: This outbreak is
      probably part of a wider one diffusing among high level judo teams. Stopping it
      requires the cooperation of several distinct actors, among which sports
      federations as well as sports-related physicians and dermatologists should play a
      major role.

PMID- 16885839
TI  - [Sirolimus-induced onychopathy in renal transplant recipients].
AB  - INTRODUCTION: A large number of drugs may be responsible for the development of
      nail changes. Sirolimus is an immunosuppressive drug recently developed in organ
      transplantation. Herein, we evaluate sirolimus-induced nail abnormalities in
      renal transplant recipients. PATIENTS AND METHODS: The nails of 80 consecutive
      renal transplant recipients receiving sirolimus have been evaluated in a
      systematic dermatological study in 2003. The patients were mainly men (60%) with
      a mean age of 48 years. The mean duration of the graft was 6 years and of
      sirolimus treatment 18 months. Mycophenolate mofetil and steroids were combined
      with sirolimus in 86% of patients. RESULTS: Fifty-seven patients (74%) complained
      for nail alterations. The most frequent anomalies (88%) were matrix alterations
      including slow growth, onychomalacia, onychorrexis, and leukonychia. Nail bed
      alterations (onycholysis), vascular phenomenon (erythema, splinter hemorrhages),
      and periungual anomalies (mainly pyogenic granulomas) were observed in 42, 42 and
      19% of cases respectively. One observation of type 1 photo-onycholysis was
      described. DISCUSSION: This study reports a new drug-induced onychopathy.
      Responsibility of sirolimus is highly suggested. The main pathogenesis hypothesis
      to explain these nail alterations is inhibition of EGF (epidermal growth factor)
      pathway by sirolimus.

PMID- 16885840
TI  - [Cutaneous leishmania in HIV patient in Ouagadougou: clinical and therapeutic
      aspects].
AB  - BACKGROUND: Immune suppression cause by HIV infection is a risk factor in the
      progression of leishmania diseases. In Burkina Faso atypical clinical
      presentations of leishmaniases have been observed among people living with HIV.
      The goal of this study was to describe clinical and evolutionary aspects of
      cutaneous leishmania and HIV co-infection among patients followed at Ouagadougou
      University Hospital. PATIENTS AND METHODS: This 16-month prospective study was
      carried out from January 2003 to April 2004 among HIV-seropositive patients with
      a diagnosed cutaneous leishmania infection. At baseline, infection and lesions
      were classified. Clinical diagnosis of cutaneous leishmania depended on finding
      parasites by microscopy in smears or tissue biopsies. Histological examinations
      were done if clinical and parasitological diagnosis were not concordant.
      Treatment consisted of three 21-day rounds of pentavalent antimonial,
      (Glucantime(R)). Clinical evolution was monitored at the end of each treatment
      round. RESULTS: Thirty-two HIV-1 positive patients (16 women and 16 men) were
      included. Mean age was 35.5 (10-67 years old). Leishmania lesions had been
      evolving, on average, for 12 weeks. Eleven patients were taking HAART and 21
      patients were taking cotrimoxazole prophylaxis against opportunistic infections.
      Cutaneous lesions were found: in the face (15 cases), torso (18 cases),
      upperlimbs (26 cases) and lower-limbs (28 cases). Observed clinical forms were:
      papulo-nodular (9 cases), ulcerative (14 cases), infiltrative (12 cases),
      lepromatous and diffuse (15 cases), psoriasis-like (5 cases), cheloid, histioid
      or kaposi-like (1 case each). Some patients presented more than one clinical
      form. Prognosis was satisfactory in 24 patients after the first treatment. Twelve
      patients relapsed after the first treatment, among those 10 were only taking
      cotrimoxazole. At the end of the third treatment, 24 patients were cured, 3 died
      and 5 were lost to follow-up. CONCLUSION: Clinical polymorphism of cutaneous
      leishmania has been observed in HIV-patients, thereby increasing the risk of
      differential diagnosis.

PMID- 16885841
TI  - [Autoimmunity induced by low doses of interferon in melanoma stage I].
AB  - INTRODUCTION: The principal aim of this work was to determine the prevalence of
      antinuclear antibodies and antinucleosomes antibodies during a treatment by
      interferon alpha with low dose for 18 months among patients with a melanoma stage
      I. The secondary objective consisted to seek the existence or not of a
      correlation with the clinical relapse, to determine the prevalence of appearance
      of clinical signs of autoimmune diseases and dysthyroidie. PATIENT AND METHODS:
      It was an exploratory study. The patients included in the study had a melanoma
      stage I (French classification), whose excision was realized for 6 weeks maximum,
      with a Breslow index equal or higher than 1,5 mm. The statistical model of
      logistic regression was used. RESULTS: Eighty-forth patients were included (38
      women and 46 men) old from 21 to 75 years. The prevalence of antinuclear
      antibodies was 39%. None of the following variables: age, sex, phototype,
      localisation of melanoma in exposed photo zone, index of Breslow or Clark, were
      significantly associated with the presence of antinuclear antibodies. As the
      percentage of patients with anti-nucleosomes was low (5%), no statistical study
      was carried out. The prevalence of clinical and/or biological dysthyroidie was
      37%. 60% of the patients presented at a moment in the evolution antinuclear
      antibodies or a dysthyroidie. The prevalence of relapses and death different was
      not correlated significantly with antinuclear antibodies and/or a dysthyroidie.
      DISCUSSION: Many studies report the appearance of antinuclear antibodies,
      generally without clinical lesions during the treatment by interferon alpha for
      cancers (tumours carcinoids, hemopathies) and viral chronic hepatitis. Our study
      is, to our knowledge, the first evaluating the induction of an autoimmunity
      during the adjuvant treatment by interferon alpha of melanoma stage I. The
      induction of autoantibody during the treatment by interferon alpha could
      constitute a marker of effectiveness of the treatment with improvement of the
      survival of these patients. In our study, however auto immunity markers do not
      appear as factors of severity of evolution of the melanoma or predictive factors.

PMID- 16885842
TI  - [Chikungunya: a case of painful rash and fever in a patient returning from the
      Indian Ocean].
AB  - A 40-year-old woman presented with invalidating polyarthritis associated with
      high fever and diffuse macular exanthema after returning from a two-week visit to
      Reunion Island. In this paper, we discuss the different diagnoses to be
      considered in a case of fever with pain and rash and we examine the epidemiology,
      clinical features, diagnostic methods and management of Chikungunya virus.

PMID- 16885843
TI  - [Giant vascular tumour in an adult: tufted angioma or kaposiform
      hemangioendothelioma].
AB  - INTRODUCTION: Tufted angioma and kaposiform hemangioendothelioma are two rare
      benign but aggressive vascular tumours that occur mainly in children.
      OBSERVATION: A 72 year-old man consulted for a 50 cm wide vascular tumour of the
      right shoulder which was increasing for 10 years. On histological examination
      there were features of tufted angioma and kaposiform hemangioendothelioma.
      DISCUSSION: The tumour of this patient was atypical because of its big size never
      described before. The histological association of aspects which could correspond
      to tufted angioma and kaposiform hemangioendothelioma seems to confirm recent
      publications which support the hypothesis that these two tumours are two
      evolutive stages of one and only entity.

PMID- 16885844
TI  - [Bullous paraneoplastic acrokeratosis].
AB  - BACKGROUND: Bullous lesions of acral distribution are an uncommon finding in
      Bazex's syndrome (acrokeratosis paraneoplastica). We report here one of these
      rare cases. PATIENTS AND METHODS: A 65 year-old-man, an alcoholic and a smoker,
      presented with characteristic lesions of Bazex's acrokeratosis paraneoplastica
      associated with a right cervical lymph node mass. An epidermoid carcinoma of
      sinus piriformis was then discovered. The acrokeratosis lesions worsened and
      spread to the knees, elbows, trunk and genitalia, with an erosive aspect, pain in
      the extremities, and tender, hemorrhagic bullous lesions on the toes and sides of
      the feet. Histological examination of a biopsy sample showed a subepidermal
      blister with numerous eosinophilic leucocytes. Direct immuno-fluorescence showed
      C3 deposits on dermal capillaries and IgA and IgM on colloid bodies in the
      papillary dermis. Blood eosinophilia and high levels of IgE were noted. Indirect
      immunofluorescence was negative for anti-epidermal and anti-basement membrane
      antibodies. Radiation and chemotherapy for the neoplasia resulted in healing of
      the bullous lesions and almost complete disappearance of keratotic squamous
      lesions with residual hyperpigmentation. DISCUSSION: Although bullous lesions are
      rare in Bazex's syndrome (acrokeratosis paraneoplastica), they were noted as
      early as 1968 by Degos et al. These acral bullae mimic autoimmune bullous
      disease. An immunological reaction is thought to occur with antigens of the
      dermal-epidermal junction and eosinophils appear to be involved.

PMID- 16885845
TI  - [Leprosy revealed by oedema of the hands].
AB  - BACKGROUND: We reported a case of lepromatous leprosy in a Tunisian woman
      revealed by a potentially misleading clinical picture involving isolated
      infiltration of the hands. PATIENTS AND METHODS: A 37 year-old woman consulted in
      October 2000 for bilateral edema of the hands associated with paraesthesia that
      had been present for one month. Screening for Hansen's bacilli confirmed the
      diagnosis of multibacillary leprosy. Daily therapy with triple anti-leprosy
      treatment was initiated. DISCUSSION: The occurrence of edema, which is
      classically described as a symptom of a reactional state, can occur during the
      course of leprosy. Where it is a presenting symptom, this unusual heralding sign
      can be a source of diagnostic error and delay.

PMID- 16885846
TI  - [Extensive cutaneous candidiasis revealing cutaneous T-cell lymphoma: 2 cases].
AB  - BACKGROUND: During the course of immunodeficiency diseases, severe candidiasis
      can occur with extensive cutaneous and mucous membrane lesions. However, blood
      dyscrasias are very rarely revealed by diffuse candidiasis. We report two case of
      cutaneous T-cell lymphoma revealed by extensive and atypical cutaneous
      candidiasis. PATIENTS AND METHODS: Case No. 1:A 72-year-old woman presented a
      pruritic rash of circinate, serpiginous patches on glabrous skin and skinfolds
      with multiple intertrigo and rapidly worsening palmoplantar keratoderma. All
      mycological skin specimens tested positive for Candida albicans. Histological
      examination of a biopsy sample from a serpiginous patch revealed the presence of
      fungal elements while palmoplantar keratoderma biopsy showed an epidermotropic
      lymphocytic infiltrate in the superficial dermis evocative of mycosis fungoides.
      Blood tests showed a white cell count of 28 600/mm3 with 14% circulating Sezary
      cells and a T-cell clone. The T-cell lymphoma was treated with methotrexate, but
      the disease worsened a few months later, progressing to CD30- large T-cell
      pleomorphic lymphoma. The patient died of severe sepsis. Case No 2:A 60-year-old
      man presented a macular rash over the face, trunk and skinfolds as well as
      erythematous scaly annular plaques of the glabrous skin with lymphadenopathy.
      Cultures of skin scrapings were all positive for Candida albicans. Blood tests
      showed a white cell count of 15 000/mm3 with 30% circulating Sezary cells. A
      trunk patch biopsy revealed the histological appearance of mycosis fungoides.
      There was a T-cell clone in the peripheral blood and skin. DISCUSSION: In both
      cases, the patients presented with widespread annular and erythematous scaly
      lesions of the glabrous skin and skinfolds with evidence of Candida albicans on
      fungal tests of all skin scrapings. The discovery of circulating Sezary cells on
      a systematic smear for hyperleukocytosis led us to suspect underlying cutaneous T
      cell lymphoma, which was confirmed by biopsy of the skin lesions accompanying the
      mycoses. Widespread cutaneous candidiasis can occur in patients with cell
      mediated immunodepression. Cutaneous T-cell lymphoma can enhance such candidiasis
      through interference with skin integrity and impairment of cell-mediated
      immunity, with large amounts of IL10 and TGF-B, increased secretion of soluble
      interleukin-2 receptors (CD25) and impaired CD8 suppressor cell function.

PMID- 16885847
TI  - [Giant sebaceous gland hyperplasia of the vulva].
AB  - BACKGROUND: Sebaceous gland hyperplasia is an epithelial tumour with sebaceous
      differentiation. Genital involvement is rare. In this paper, we report a new case
      of sebaceous gland hyperplasia of the vulva. CASE REPORT: A 27 year-old woman
      presented multiple polypoid lesions of the lower third of left labium majus. The
      lesions were soft to the touch, measured 5 cm in length and were painless. The
      cutaneous biopsy confirmed the diagnosis of sebaceous gland hyperplasia of the
      vulva. Surgical excision was performed in two separate procedures and was
      successful. DISCUSSION: This case was unusual in terms of the site, the clinical
      appearance and the weeping seen due to the high concentration of hyperplasic
      sebaceous glands.

PMID- 16885848
TI  - [Regression of primary melanoma with metastases associated with amyopathic
      dermatomyositis].
AB  - BACKGROUND: Dermatomyositis is a rare and serious inflammatory connective tissue
      disease characterized by a typical cutaneous rash and myopathy. Amyopathic
      dermatomyositis is a particular form of dermatomyositis involving only cutaneous
      signs and without myopathy present for over 2 years. PATIENTS AND METHODS: A 48
      year-old woman presented with a 3-year history of cutaneous rash without myopathy
      characteristic of amyopathic dermatomyositis. Clinical examination revealed
      extensive axillary adenopathy, histological examination of which suggested
      secondary melanoma. The patient reported a black nevus in the axillary area that
      had disappeared 1 year earlier. Curettage of the lymph node was negative and the
      patient was treated with interferon (3M 3 times a week). Regression of the
      cutaneous signs was noted. DISCUSSION: The data, there have been no other reports
      of paraneoplastic amyopathic dermatomyositis associated with regression of
      primary melanoma. The literature contains few reports of dermatomyositis
      associated with melanoma. Amyopathic dermatomyositis may be associated with
      malignancy.

PMID- 16885850
TI  - [Transcriptoma and melanoma: physiopathological and therapeutic implications].

PMID- 16885849
TI  - [Electromagnetic lipolysis and semicircular lipoatrophy of the thighs].
AB  - INTRODUCTION: The semicircular lipoatrophy of the thighs is a disorder whose
      incidence remained rare for years. Only recently, an "epidemic" situation
      emerged, affecting hundreds of subjects who shared a status of administrative
      employee. OBSERVATION: The older etiopathogenic hypotheses give way to a newer
      one implying the electromagnetic fields generated by computers and their wirings.
      The resulting modifications in the intrinsic bioelectrical properties of the skin
      could influence the biology of macrophages exhibiting lipophagic activity in the
      hypodermis. The electroactivation of these cells could lead to TNF-alpha release.
      DISCUSSION: The semicircular lipoatrophy of the thighs is a problem that may
      affect an employee out of two. Rather than hoping an efficaceous drug therapy,
      prevention must be advocated by adapting the work conditions related to the use
      of computerized devices.

PMID- 16885851
TI  - [Vulvar involvement in Crohn's disease: efficacy of metronidazole].

PMID- 16885852
TI  - [Linear IgA bullous dermatosis associated with celiac disease].

PMID- 16885854
TI  - [About the article "What's new in dermatology?"].

PMID- 16885853
TI  - [Palpebral and ocular manifestations of atopic dermatitis].

PMID- 16885855
TI  - [Facial rash].

PMID- 16885856
TI  - [Crusted erythematous preauricular lesion].

PMID- 16885857
TI  - [Cystic lymphatic malformations].

PMID- 16885858
TI  - [Facial granuloma].

PMID- 16885859
TI  - [Palmoplantar keratodermas: news from the front].

PMID- 16885860
TI  - [Urticaria-like mucinosis].

PMID- 16885861
TI  - [Ecthyma gangrenosum: 3 cases].

PMID- 16885862
TI  - [TL01 UVB phototherapy and demodex-induced folliculitis].

PMID- 16885863
TI  - The quest for new therapies in patients with cirrhosis and sepsis. Time to move
      from the lab to the bedside.

PMID- 16885864
TI  - Liver abscess after radiofrequency ablation of tumors in patients with a biliary
      tract procedure.
AB  - AIM: The rate of liver abscesses after radiofrequency ablation (RFA) of liver
      tumors is probably high in patients with a biliary tract drainage procedure
      connecting the biliary duct system to the upper gastrointestinal tract. And yet,
      to date this rate, the time of onset of these abscesses, and the prior status of
      the bile ducts have never been reported in the literature. METHODS: Among 574
      patients treated with RFA over 8 years, only 11 patients (with 13 sessions of
      RFA, 2 patients undergoing two different RFA sessions) presented with an
      enterobiliary anastomosis or biliary stenting at the time of RFA. This is a
      retrospective study of patients who were verified prospectively. RESULTS: Among
      the 9 patients in whom a biliary tract procedure preceded RFA, 4 developed a
      liver abscess at the site of RFA, which emerged between 13 and 62 days after RFA.
      It occurred in spite of different types of short-term antibiotic prophylaxis.
      Pathogenic bacteria were typical of the digestive flora. Abscesses were cured
      after percutaneous drainage. No abscess occurred among the 4 patients in whom a
      biliary tract diversion was performed synchronously with RFA. CONCLUSION: When
      RFA is performed in a patient with a preexisting biliary diversion, the risk of
      developing a liver abscess is high. Currently, we are unable to recommend any
      kind of preventive antibiotherapy. A preexisting biliary diversion is not an
      absolute contraindication for RFA, but the risk of developing a liver abscess is
      close to 40-50%. When RFA is performed synchronously with a biliary diversion,
      the risk of a liver abscess seems to disappear.

PMID- 16885865
TI  - [Transvisceral endoscopic surgery: a new type of laparoscopy or
      gastroenterological surgery?].

PMID- 16885866
TI  - Colorectal cancer screening in Health Examination Centers.
AB  - OBJECTIVES: The aim of this study was to describe the results of colorectal
      cancer screening performed in the Health Examination Centers of the French
      general health insurance system. METHODS: The population consisted of 1,262,833
      subjects (52.6% men) aged 50 to 74 years old who attended periodic health
      consultations from 1998 to 2003 in 89 Health Examination Centers in France.
      Subjects with increased risk for colorectal cancer and subjects with a positive
      fecal occult blood test (Hemoccult II') were invited to undergo colonoscopy.
      Subsequent follow-up and diagnostic data were collected. RESULTS: Prior screening
      practices for colorectal cancer (recent colonoscopy or fecal occult blood test,
      local screening campaign) were noted in 18% of the subjects attending Health
      Examination Center consultations. High risk for colorectal cancer (familial or
      personal factor) without ongoing surveillance or prior screening was observed in
      3% of the study population. A fecal occult blood test was proposed to 79% of the
      population and of them, 89% effectively performed the test: 3.2% of tests were
      positive. A follow-up protocol was initiated for 63,357 subjects. A colonic
      exploration was performed in 69% of high-risk subjects and enabled detection of
      cancer in 85 and adenomas in 1683. A colonic exploration was performed in 88% of
      subjects with a positive fecal occult blood test and enabled detection of 674
      cancers (positive predictive value of fecal occult blood test (PPV)=4.7%)
      including 174 Dukes A, and 2618 adenomas (PPV=18%) including 776 adenomas
      measuring more than 10 mm (PPV=5.4%). CONCLUSION: This study confirms the
      importance of implementing organized screening practices within Health
      Examination Centers before undertaking a generalized screen campaign targeting
      the entire French population.

PMID- 16885867
TI  - Estimation of the prevalence and incidence of chronic pancreatitis and its
      complications.
AB  - Incidence and prevalence of chronic pancreatitis (CP) are poorly known and
      prospective nationwide epidemiologic estimation has never been performed. AIMS:
      To estimate prospectively national incidence and prevalence of patients attending
      gastroenterologists for CP in France. PATIENTS AND METHODS: Study was proposed to
      all of the French gastroenterologists (N=3215) of whom 753 accepted to
      participate (24% private, 40% hospital and 36% both). Were included all patients
      suffering from proved or suspected CP, from 04-2003 to 07-2003. Certain
      diagnostic criteria were pancreatic calcifications, ductal or histological
      abnormalities. For all of non-responder gastroenterologists, a tracking system
      was used (mail or by phone). RESULTS: A total of 456 gastroenterologists returned
      at least 1 case on 1748 patients. Median patient age was 51 years; sex-ratio was
      5.07. Median duration between the first CP sign and the inclusion was 41 months.
      CP cause was alcoholism (84%), hereditary (1%), cystic fibrosis (1%), idiopathic
      (9%), other (6%). CP diagnosis was certain in 77%: calcifications (85%), ductal
      abnormalities (57%), and histology (8%). CP symptoms were: chronic abdominal pain
      (53%), acute pancreatitis episodes (67%), pseudocysts (40%), bi-liary tract
      compression (21%), diabetes mellitus (32%), pancreatic exocrine insufficiency
      (36%). Maximal annual incidence was 4,646 (crude annual incidence: 7.7 per
      100,000; 12.9 in male; 2.6 in female) and prevalence was 15,832 cases (crude
      prevalence: 26.4 per 100,000; 43.8 in male; 9.0 in female). CONCLUSION: New CP
      patients attending gastroenterologists are about 5,000 a year. CP prevalence is
      about 16,000 patients (in France: 60,400,000 inhabitants). Frequency of main
      complications is close to hospital series, confirming that results issued from
      these centers are not or a few biased.

PMID- 16885868
TI  - Impact of radiation schedule and chemotherapy duration in definitive
      chemoradiotherapy regimen for esophageal cancer.
AB  - Impact of radiotherapy (RT) schedule on local response and duration of the 5
      fluorouracil/cisplatin (5 FU/CDDP) chemotherapy (CT) on m are still questioning
      in chemoradiotherapy (CRT) regimen in esophageal carcinoma. AIM: Evaluate two RT
      schedules and two different CT durations by a retrospective comparison of the CRT
      regimens used by two centres between 1994 and 2000. METHODS: In centre I (regimen
      I), patients received 2 CT concomitantly to a continuous RT (50 Gy/25 fractions/5
      weeks). In centre II (regimen II), patients received 6 CT, 3 were concomitant to
      a split course RT (20 Gy/10 fractions x 3 courses) and 3 CT were delivered after
      CRT. RESULTS: A total of 129 patients were included, 74 in centre I and 55 in
      centre II respectively. Main patient characteristics were similar between the two
      groups. Clinical complete response to CRT was significantly more frequent in
      regimen I (83.8% vs 65.4%; P=0.02). The median overall survival (OS) was 20
      months in regimen I and 22 months in regimen II (NS). During follow-up, responder
      patients to CRT in regimen II experienced significant fewer metastasis (51.6% vs
      27.8%; P=0.03) with a trend to an increased 5-year survival (19.4% vs 11.3%) and
      OS (26.5 vs 21.0 months) (NS). Grade 3-4 toxicities were not different.
      CONCLUSION: Clinical complete response to CRT was significantly more frequent
      with a continuous RT whereas additional CT after CRT significantly reduced
      metastasis occurrence. CRT regimen in esophageal carcinoma may be more effective
      using a continuous RT schedule and additional CT courses after CRT completion.

PMID- 16885869
TI  - Assessment of management practices for colonic cancer in the Paris metropolitan
      area in 2002.
AB  - OBJECTIVE: To assess the management of patients aged 18 years or older with
      colonic adenocarcinoma (including the rectosigmoid junction), compared with
      French guidelines (ANAES and SOR). METHODS: This retrospective study carried out
      in 2003 by the Ile-de-France regional union of health insurance funds from
      hospital discharge and operative and pathology reports of patients exempted from
      copayment between April 2001 and March 2002. RESULTS: In all, 1 842 patients were
      included; mean age was 68.7 +/- 12.7 years and the M/F ratio was 1.09. 17.3% of
      patients were diagnosed after complications (obstruction, perforation); 25.1% had
      synchronous metastases, 79.7% with at least one liver metastasis. Serum CEA assay
      was performed in 50.0% of patients, in combination with CA 19-9 in 31.1% of
      patients. In 24.9%, less than 8 lymph nodes were analyzed. 37.7% of stage II
      patients had chemotherapy while 10.8% of stage III and 9.8% of stage IV patients
      did not. Age was a determining factor in the decision of chemotherapy (P<0.0001).
      CONCLUSION: Implementation of guidelines for the management of colon cancer can
      be improved, notably regarding pathologic analysis and indications of
      chemotherapy.

PMID- 16885870
TI  - [Environmental risk factors in Crohn's disease and ulcerative colitis (excluding
      tobacco and appendicectomy)].
AB  - A rapid increase in the incidence of Crohn's disease and ulcerative colitis in
      developed countries, the occurrence of Crohn's disease in spouses, and a lack of
      complete concordance in monozygotic twins are strong arguments for the role of
      environmental factors in inflammatory bowel disease (IBD). Research in the field
      of environmental factors in IBD is based upon epidemiological (geographical and
      case-control), clinical and experimental studies. The role of two environmental
      factors has clearly been established in IBD. Smoking is a risk factor for Crohn's
      disease and a protective factor for ulcerative colitis; appendectomy is a
      protective factor for ulcerative colitis. Many other environmental factors for
      IBD have been investigated, including infectious agents, diet, drugs, stress and
      social status. They are detailed in the present review. Among them, atypical
      Mycobacteria, oral contraceptives and antibiotics could play a role in Crohn's
      disease. To date, three hypotheses associate environmental factors with the
      pathophysiology of IBD (loss of tolerance of intestinal immune system towards
      commensal bacterial flora): the hygiene, infection and cold chain hypotheses.
      Much work remains to be done to identify risk factors for IBD. Research
      identifying environmental factors that might cause a predisposition to IBD is
      useful. It may lead to disease prevention in subjects who are genetically
      predisposed and disease improvement in patients.

PMID- 16885871
TI  - [Ascitic decompensation].

PMID- 16885872
TI  - [Rupture of esophageal varices].

PMID- 16885873
TI  - [Should we screen for hepatocellular carcinoma?].

PMID- 16885875
TI  - [Infection during cirrhosis].

PMID- 16885874
TI  - [Palliative treatment of hepatocellular carcinoma].

PMID- 16885876
TI  - [Antiviral treatments during cirrhosis].

PMID- 16885877
TI  - [Ascites due to portal hypertension from breast cancer- related metastatic liver
      infiltration].
AB  - Ascites in patients with breast cancer is uncommon. We report the case of a 70
      year-old woman with breast cancer and ascites caused by portal hypertension due
      to metastatic liver infiltration. There was no evidence of peritoneal
      carcinomatosis and the prothrombin index was normal. Portal hypertension was
      confirmed by increased hepatic venous pressure gradient. Histological examination
      of a liver biopsy obtained by the transjugular route demonstrated infiltration by
      malignant cells from the breast tumor. This case shows that, infiltration of the
      liver by metastases from breast cancer may lead to ascites due to portal
      hypertension, even in the absence of hepatic failure.

PMID- 16885878
TI  - [Corticotherapy and giant hemangioma of the liver. Return to the normal values of
      cytokines].
AB  - We report the case of a 36 year-old woman presenting with a giant liver
      hemangioma revealed by febrile hepatomegaly and weight loss. The patient
      presented an inflammatory syndrome without hyperleucytose, anemia and a moderate
      anicteric cholestasis. Plasma concentrations of interleukine-6 were very high
      whereas interleukine-1 levels were relatively low and TNF levels were normal.
      Eight weeks of corticosteroid treatment (prednisone 40 mg/d) resulted in
      disappearance of symptoms after 48 hours and biological anomalies after 6 weeks.
      Clinical and radiological follow-up, for respectively 36 and 24 months, did not
      show any relapse of symptoms or evolution of the hemangioma.

PMID- 16885879
TI  - [Autoimmune pancreatitis: beneficial effects of corticosteroid therapy on biliary
      and metabolic complications].
AB  - Auto-immune pancreatitis is rare and its evolution includes both the usual
      complications of chronic pancreatites, such as diabetes and specific consequences
      and complications including extension of inflammatory lesions of the extra or
      intrahepatic biliary tract. One particular characteristic of these complications
      is that they are sensitive to cortisone therapy, as illustrated by the case we
      report here.

PMID- 16885880
TI  - [Single filiform polyp revealed by severe haemorrhage in a patient with normal
      colon. Report of a case and review of the literature].
AB  - Filiform polyposis or giant inflammatory polyp is an uncommon benign lesion that
      has principally been reported in patients with evidence of inflammatory bowel
      disease, Crohn's disease or ulcerative colitis. It appears to be a sequella of
      diffuse mucosal inflammation. More rarely, PF found in association with colonic
      non specific inflammation. PF has rarely been reported in patients without
      previous colonic disease. We report the case of a 60-year-old woman without
      history of colonic disease who presented a PF revealed by hematochesia.

PMID- 16885881
TI  - [Autoimmune hepatitis and morphea: a rare association].

PMID- 16885882
TI  - [Gougerot-Sjogren syndrome and achalasia].

PMID- 16885883
TI  - [Meckel's diverticulum with lower digestive hemorrhage and perforation].

PMID- 16885884
TI  - An adult case of acute intra abdominal organoaxial gastric volvulus.

PMID- 16885885
TI  - [Calcic involution of a serous cystadenoma].

PMID- 16885886
TI  - [Acute spontaneous corneal hydrops in a patient with pellucid marginal corneal
      degeneration].
AB  - Pellucid marginal corneal degeneration (PMCD) is an ectatic corneal disorder
      characterized by a peripheral, noninflammatory band of thinning of the inferior
      cornea. This condition often is misdiagnosed with keratoconus, with which it
      shares several clinical, videotopographic, and histologic aspects. Furthermore,
      as with keratoconus, hydrops and spontaneous corneal perforation can occur. We
      report the case of a 56-year-old man with confirmed PMCD, emphasizing the
      diagnostic approach, the disease follow-up, and its complication in spontaneous
      acute corneal hydrops. Finally, regarding this case, authors collect the clinical
      and videotopographic characteristics of PMCD and discuss the different
      therapeutic options.

PMID- 16885887
TI  - [Rat bite: an unusual cause of orbital cellulitis].
AB  - Rat bite is rarely reported in the literature. We report the case of a 33-year
      old woman who was bitten by a rat on her upper eyelid. The clinical examination
      showed a large palpebral edema extending to the side of the face, associated with
      local signs of inflammation. Visual acuity was preserved and tomodensitometry
      showed a small exophthalmia that did not extend to the sinuses. This lesion led
      to a diagnosis of orbital cellulitis. Progression was favorable with antibiotics:
      amoxicillin, clavulanic acid, gentamicin, and metronidazole. The authors discuss
      the compromised prognosis of this disease and the necessity of rapid diagnosis
      and prompt therapeutic management.

PMID- 16885888
TI  - [Clinical study of Supranettes pads in the treatment of seasonal or perennial
      allergic conjunctivitis in children].
AB  - PURPOSE: Ocular allergy is a common disease that is on the rise. Seasonal and
      perennial conjunctivitis are the most common forms of ocular allergy. Itching,
      hyperemia, foreign body sensation, irritation, blurred vision or ocular dryness
      sensations, tearing, and photophobia are the clinical signs observed in patients.
      A topical antiallergic treatment is prescribed associated with ocular cleaning to
      contribute to an antigen washing of the ocular surface. Our study aimed to
      evaluate the use of Supranettes pads as supplementation treatment in children for
      seasonal or perennial conjunctivitis. MATERIAL AND METHODS: Our prospective study
      was done in children with a diagnosis of seasonal or perennial clinical ocular
      allergy. Every symptom was rated from 0 to 4 according to the intensity described
      by the children and their parents. Twenty children (range, 4-10 years) presenting
      an ocular allergy were included in the study. A topical antiallergic treatment
      membrane stabilizer or antihistamine and Supranettes pads were prescribed for
      ocular cleaning of one randomized selected eye four times a day. Patients were
      seen in consultation 1 month later to evaluate the treatment. The ocular comfort
      of each eye, one treated with Supranettes pads and the other not treated by
      Supranettes pads, was evaluated by the child helped by parents on a graduated
      self-evaluation scale (range, 0-10). The Mann-Whitney statistical test was used
      to differentiate the two groups. RESULTS: Of the 20 patients, eleven presented
      seasonal conjunctivitis and nine perennial conjunctivitis. Six of them presented
      conjunctivitis with a slight to moderate superficial punctuate keratitis. At the
      consultation on day 28+/-3, patients who were first treated showed clear
      improvement of clinical signs with the prescribed treatment. The statistical
      comparison of the two groups confirmed a significant difference (p<0.05) to the
      advantage of the group using the Supranettes pads. DISCUSSION: Ocular washing is
      essential in the treatment of allergic conjunctivitis. The new galenic form of
      ocular cleaning by physiological serum-impregnated pads is simple to use for
      children. An objective significant difference is difficult to observe in 1 month.
      CONCLUSION: This study underlines the importance of the comfort of Supranettes
      pads evaluated in the treatment of children's conjunctivitis. It confirms the
      advantage of developing evaluation studies including patient satisfaction and
      quality of life in ophthalmology.

PMID- 16885889
TI  - [Deep anterior lamellar keratoplasty in the surgical treatment of keratoconus. A
      1-year follow-up].
AB  - OBJECTIVE: To evaluate the results of deep anterior lamellar keratoplasty (DALK)
      using dissection with air or with a viscoelastic substance in the surgical
      treatment of keratoconus as an alternative to penetrating keratoplasty. MATERIAL
      AND METHODS: This prospective monocentric noncomparative study involved patients
      with contact lens-intolerant keratoconus operated on between February 2001 and
      September 2002. Deep lamellar dissection was performed either by air injection
      into the cornea to create a white emphysema of the stroma or by viscoelastic
      injection. This allows the surgeon to separate Descemet's membrane from the
      posterior stroma using the air-to-endothelium interface. Previously, aqueous
      humor was replaced by air in the anterior chamber to visualize the posterior
      corneal surface. A full-thickness allogenic corneal button was sutured into the
      recipient bed, after stripping its Descemet's membrane. RESULTS: Fifteen eyes of
      15 patients (mean age, 41.2 years) underwent DALK. The mean preoperative visual
      acuity was 0.11+/-0.06. At 1 year, the mean best corrected visual acuity was
      0.47+/-0.16 (p<0.001). Mean keratometric astigmatism was reduced from 6.97+/-3.3
      D to 2.77+/-1.76 D at 1 year (p<0.001). Specular microscopy 3 months
      postoperatively revealed average endothelial cell counts of 2018+/-662/mm2, while
      1 month preoperatively this value was 2604+/-235/mm2 (cell loss, 22.5%; p>0.05).
      Perforation of Descemet's membrane during surgery occurred in five eyes (33.3%).
      Two cases were converted to penetrating keratoplasty. There was no endothelial
      rejection. CONCLUSION: In this series, DALK appears to be a promising procedure
      for treatment of keratoconus with encouraging refractive outcome, no progressive
      primary graft failure, and no allogenic endothelial graft rejection. DALK is an
      interesting alternative for penetrating keratoplasty even if it is technically
      more difficult.

PMID- 16885890
TI  - [Efficacy of first- or second-line latanoprost on intraocular pressure and ocular
      symptoms in patients with open-angle glaucoma or ocular hypertension].
AB  - OBJECTIVES: The aim of this study was to assess the changes in intraocular
      pressure (IOP) and ophthalmic symptoms with the Glaucoma Symptom Scale in
      patients suffering from open-angle glaucoma (OAG) or ocular hypertension (OHT)
      after 3 months of treatment with latanoprost. MATERIALS AND METHODS: This
      multicentric open study was carried out in adult patients suffering from OAG or
      simple OHT (naive or previously treated with monotherapy) and needing a change or
      initiation of anti-glaucomatous treatment. One drop of latanoprost 0.005% was
      instilled every evening for 12 weeks in each affected eye. Efficacy was assessed
      by the variation in IOP and ophthalmic symptomatology at the end of treatment.
      Prognosis factors associated with a relative IOP reduction of at least 30% were
      sought (using a logistic regression model). RESULTS: A total of 920 patients
      suffering from OAG (54%) or OHT (44%), either previously treated (69%) or naive
      (31%), were included. The male:female ratio was 0.78 and the mean age was 63+/-13
      years. At inclusion, the mean IOP was 22.1+/-3.8 mmHg. After treatment, IOP was
      significantly decreased by 5.1+/-4 mmHg, corresponding to a 22% reduction. IOP
      reduction was 7.1+/-4 mmHg, corresponding to 29% in naive patients and 4.2+/-4
      mmHg, corresponding to 19% in previously treated patients. A relative IOP
      reduction of at least 30% was reached by 47% of naive patients and 21% of
      previously treated patients. In previously treated patients, a relative IOP
      reduction of at least 30% had a greater chance of being reached in men with
      previous ophthalmic history and high IOP at inclusion (above 21 mmHg). IOP
      reduction was similar in patients with OAG and OHT. A significant improvement in
      ophthalmic symptoms was observed after treatment in previously treated patients.
      A total of 7% of the patients presented an adverse event affecting the visual
      system: eye irritation (2%), eye pain (2%), or eye hyperemia (1%). Compliance was
      good for 94% of the patients. CONCLUSION: Latanoprost given as first or second
      line treatment at the recommended dose effectively decreases IOP in patients with
      OAG or OHT. This treatment also improves visual and nonvisual symptoms in
      previously treated patients and presents a good safety profile.

PMID- 16885891
TI  - [Argon laser iridoplasty in the treatment of angle closure glaucoma with plateau
      iris syndrome].
AB  - INTRODUCTION: Plateau iris predisposes to the onset of an angle-closure glaucoma
      attack without pupillary block. This is a morphological anomaly of the iris
      characterized by anterior insertion, root thickness greater than the norm, and
      anterior rotation of the ciliary processes into the posterior chamber, pushing
      the base of the iris into the angle. Argon laser iridoplasty is useful to retract
      the peripheral iris using the thermal effect of the laser to widen the
      iridocorneal angle. MATERIALS AND METHODS: The study investigated nine eyes of
      five patients who had had iridoplasty for iris plateau angle-closure glaucoma,
      diagnosed by dynamic gonioscopy (or indentation gonioscopy) and confirmed by
      ultrasound biomicroscopy (UBM). There were four females and one male, with a mean
      age of 42.2 years (range, 30-53 years). The mean intraocular pressure (IOP)
      before iridoplasty was 21.1 mmHg. The number of antiglaucoma treatments was 1 or
      2, with all patients receiving miotic treatment. All patients had undergone argon
      laser iridotomy beforehand to remove the pupillary block frequently associated
      with iris plateau. Iridoplasty was done in two sessions with postoperative IOP
      lowering treatment. The laser parameters used were: duration, 0.3 s; power, 500
      mW; diameter, 300 microm. RESULTS: The postoperative IOP evaluated at 1 month was
      14.4 mmHg with a reduction in the hypotensive treatment. No treatment was
      prescribed for four eyes, a single hypotensive treatment for four eyes, and two
      hypotensive medications for one eye. DISCUSSION: Pure iris plateau syndrome,
      leading to closure of the angle, is very rare compared to pupillary block, but
      these two mechanisms often co-exist. The physiopathology explains that the
      mechanism of isolated iris plateau is not modified by iridectomy. However, the
      advantage of argon laser iridoplasty, which retracts the periphery of the iris so
      as to widen the iridocorneal angle, must be emphasized. This technique can
      alleviate the need for high-risk filtering surgery, but longer follow-up is
      necessary to evaluate its duration and efficacy.

PMID- 16885892
TI  - [What do we know about intraocular pressure in the Togolese population?].
AB  - BACKGROUND: Intraocular pressure is a major ocular risk factor of chronic open
      angle glaucoma. This study aimed to describe characteristics of intraocular
      pressure in a defined black African population. METHODS: Hospital outpatients
      were recruited for this study, and all measures were taken with a pulse air
      tonometer between 8 AM and 12 AM; some participants were glaucoma patients under
      medical treatment. On the whole, 7,042 participants (13,831 eyes) were included
      in this study. RESULTS: The mean age of all participants was 41 +/- 18 years:
      9.9% were under 16 years of age; 21.2% were between 35 and 44 years old. The
      average intraocular pressure was 17.05+/-5.93 mmHg; for the subgroup under 16
      years of age. Girls had higher pressure than boys: 16.01 vs 16.32 mmHg in the
      right eye. For those over 16 years of age, pressures were higher in men, with an
      average of 17.45 mmHg vs 16.67 mmHg in the right eye. High intraocular pressure
      was found in 22.28% of the participants, with values ranging from 20 to 29 mmHg
      in 86.8% of cases. The relative prevalence of hypertony seems to increase with
      age, reaching 30% for those aged 55-64 years. CONCLUSION: There is a high rate of
      hypertony in our findings, which seems to correlate with the increased glaucoma
      prevalence already described in the Togolese population. We concluded that in our
      setting, the prevention of glaucoma in isolated hypertonies and the management of
      glaucomatous cases warrant a thorough assessment of intraocular pressure at all
      ages.

PMID- 16885893
TI  - [Prevalence of intraocular hypertension and glaucoma in a nonselected French
      population].
AB  - AIMS: To measure intraocular pressure (IOP) in a large human sample and to assess
      the prevalence of glaucoma with elevated IOP and ocular hypertension (OHT) in
      this population. METHODS: We measured IOP in 2,074 subjects (men: women: 1,384:
      690). If the IOP was higher than 20 mmHg, a photograph of the optic disc was
      taken and the visual field was examined. The optic nerve head and the visual
      field were evaluated in 395 individuals. RESULTS: In men aged 18-39 years, mean
      IOP was 15.5+/-3.1 mmHg and 16.4+/-3.5 mmHg after 60 years of age. In women, IOP
      reached 14.5+/-3.3 and 15.9+/-3.1 mmHg, respectively. IOP greater than 21 mmHg
      was found in 10.1% of males and 6.4% of females. The prevalence of OHT increased
      with age: from 5.3% to 15.5% in men and from 3% to 7.5% in women for the same age
      ranges. A diagnosis of glaucoma with elevated IOP was made in 2.2% of males and
      3.0% of females. The prevalence of glaucoma increased with age from 0.8% to 5.7%
      in men and from 0.6% to 4.7% in women under 40 years and over 60 years of age,
      respectively. DISCUSSION: This study confirms the increase in IOP with age and
      the role of aging in the prevalence of OHT and glaucoma with elevated IOP.
      CONCLUSION: This transversal study shows the feasibility of intraocular
      hypertension and glaucoma screening and prevalence assessment in a nonselected
      large population in France.

PMID- 16885894
TI  - [Severe chloroquine- and hydroxychloroquine-induced retinopathy].
AB  - INTRODUCTION: Antimalarial drug-induced retinopathy was first described in the
      1950s. Irreversible retinal damage still occurs 50 years later, despite knowledge
      of the phenomenon. This raises several questions: How aware are physicians of
      this problem and do they inform their patients? What efficient prevention
      strategies should be advocated and what are the legal aspects? We present four
      cases of severe chloroquine- and hydroxychloroquine-induced retinopathy to try to
      understand what led to these situations. CASE REPORTS: The fist case, a male
      patient born in 1956, had chloroquine therapy for lupus initiated in 1987, at a
      dose ranging from 3 to 6 mg/kg per day. In 1992, no toxicity was clinically or
      electrophysiologically noted. In 1997, macular abnormalities were diagnosed;
      chloroquine treatment was nevertheless continued. In 2002, the electroretinogram
      and central visual field examinations were abnormal. Chloroquine treatment was
      discontinued. In 2005, abnormalities of full-field and multifocal
      electroretinograms, electro-oculogram, color vision, and visual field confirmed
      the maculopathy. The second case, a female patient, born in 1956, had chloroquine
      therapy for rheumatoid arthritis beginning in 1993, at a dose of 5 mg/kg per day.
      In 1999, 2000, and 2001, electroretinograms were reported as normal. Clinical
      maculopathy occurred in 2003 and treatment was continued. In January 2004, the
      central visual field was found abnormal; treatment was discontinued in July 2004.
      The third case, a female patient born in 1931, had chloroquine therapy for
      malaria prevention initiated in 1975, at a dose of 1.7 mg/kg per day. No exams
      were performed after 1983. In 2001, she complained of a left unilateral vision
      loss. Bilateral maculopathy was clinically found, and confirmed by full-field and
      multifocal electroretinograms. The fourth case, a female patient born in 1944,
      had hydroxychloroquine therapy for lupus initiated in 1982 at a dose of 6.9 mg/kg
      per day. In 2000 and 2002, full-field electroretinograms were reported as normal
      despite low amplitudes. In 2004, clinical examination was normal, whereas
      electroretinogram, electro-oculogram, color vision, and central visual field
      examinations proved severe damage; the treatment was discontinued. DISCUSSION:
      Retinal damage in these cases was caused by several factors. Treatment was not
      stopped despite clinically obvious maculopathy in cases 1 and 2. In case 3, no
      ophthalmologic examinations were performed between 1983 and 2001. In case 4,
      despite a high cumulative dose, therapy was not discontinued, as also seen in
      cases 1 and 2, in which ophthalmologic monitoring was not increased. Higher doses
      than the maximal recommended daily dose occurred in cases 1, 2, and 4.
      CONCLUSION: Antimalarial drug therapy still requires intensive monitoring to
      avoid severe retinal damage that can lead to legal blindness. Appropriate
      examinations should be performed regularly in order to decide whether to taper or
      stop when damage is still mild, preclinical, or reversible.

PMID- 16885895
TI  - [Corneal transplantation of a corneal graft with radial keratotomy].
AB  - INTRODUCTION: We report the case of a patient operated on for penetrating
      keratoplasty with a corneal graft with radial keratotomy. CASE REPORT: A 27-year
      old man underwent penetrating keratoplasty for keratoconus. Graft incisions of
      radial keratotomy were discovered the day after surgery. Corneal graft
      examination and endothelial cell density were carried out postoperatively.
      CONCLUSION: This case shows the potential problem of corneal graft assessment
      before transplantation. An examination of the donor's cornea before its removal
      with a portable slit lamp could make graft quality evaluation safer.

PMID- 16885896
TI  - [Sebaceous tumors of the eyelids in a patient with Muir-Torre syndrome].
AB  - Muir-Torre syndrome is an autosomal dominant hereditary condition predisposing to
      cancer. It is characterized by cutaneous tumors (such as sebaceous adenomas,
      epitheliomas, or carcinoma, and/or keratoacanthomas) and internal malignancies. A
      47-year-old male patient with cancer antecedents consulted for two tumors of the
      eyelid. Histological study of the exeresis biopsies of the eyelid lesions showed
      a sebaceous adenoma and an epidermoid carcinoma with sebaceous differentiation.
      With the suspicion of Muir-Torre syndrome, a genetic consultation was requested.
      The geneticist found a mutation of the MSH2 gene, which was not classified as
      pathological. Cancer screening was begun for the patient and his descendants. The
      clinical outcome was death from urothelial carcinoma. Eyelid sebaceous tumors
      require complete medical check-up in search of carcinoma. Demonstrating Muir
      Torre syndrome allows the medical team to propose early cutaneous and visceral
      carcinoma screening for patients, their collaterals, and their descendants.

PMID- 16885897
TI  - [DRESS syndrome with bilateral panuveitis, elevated intraocular pressure, and HHV
      6 reactivation: a case report].
AB  - INTRODUCTION: DRESS syndrome (drug rash or reaction with eosinophilia and
      systemic symptoms) is a rare but life-threatening drug hypersensitivity syndrome
      with a potential viral cofactor. The syndrome is characterized by rash, fever,
      hematological disorders (eosinophilia, lymphocytosis), and systemic symptoms
      (adenopathy, multiorgan involvement). CASE REPORT: We report the first
      description of acute bilateral panuveitis with elevated intraocular pressure
      associated with anticonvulsant-induced DRESS syndrome, hypogammaglobulinemia, and
      HHV-6 reactivation in a 63-year-old-woman. Complete general and ophthalmological
      recovery was obtained 4 weeks after the end of anticonvulsant drug exposure
      without corticosteroid prescription, with the patient remaining free of disease
      after 6 months. DISCUSSION: Our data suggest that uveitis may be one of
      multivisceral involvements described in drug hypersensitivity syndrome. The data
      also suggest that HHV-6 may play a role in the complex pathogenesis of DRESS as
      well as in the development of immune inflammatory disorders such as bilateral
      panuveitis with elevated intraocular pressure and alteration of retinal and
      choroidal circulation in this patient.

PMID- 16885898
TI  - [Bilateral infectious keratitis in a patient wearing cosmetic soft contact
      lenses].
AB  - We report a case of an immunocompetent 20-year-old woman, wearing planocosmetic
      contact lenses to change the color of her eyes, with no contact lens hygiene
      regimen. She developed a bilateral infectious keratitis. Acanthamoeba and
      Fusarium solani were isolated in both eyes. Bilateral penetrating keratoplasty
      was needed because of bilateral corneal perforation. Three months later,
      bilateral simultaneous phacoemulsification was performed because of a dense
      cataract and a severe decrease in her vision. Six months after surgery, her best
      corrected visual acuity was 0.7 in the right eye, and 0.6 in the left eye.
      Cosmetic contact lenses expose the wearers to the same potential ocular
      complications as other contact lenses. Wearers must be informed of such
      complications, which may be sight-threatening. Based on this case, we strongly
      recommend that all cosmetic contact lens wearers be examined and followed as if
      they were standard contact lens wearers.

PMID- 16885900
TI  - [Pathology of the eyelid in elderly patients].
AB  - OBJECTIVE: Didactic review of the various features of eyelid pathology in elderly
      patients. METHODS: Illustrated review centered on diagnosis of the usual aspects
      and pitfalls of eyelid pathology divided into semiological chapters (tumors,
      blisters, erythema, etc.). RESULTS: Pathology of the eyelids in elderly patients
      is extremely polymorphic. It is mainly centered on skin cancers (basal cell
      carcinoma, squamous cell carcinoma, adnexal carcinomas, and melanoma). Most
      severe aspects of the inflammatory diseases of the eyelid are bullous diseases
      (cicatricial pemphigoid, pemphigus, Stevens-Johnson syndrome, etc.). A number of
      rare diseases deserve mention since their presence could lead to the diagnosis of
      internal or systemic diseases (dermatomyositis, necrobiotic xanthogranuloma,
      Erdheim-Chester, etc.). In such conditions, early diagnosis is often based on the
      observation of isolated periocular symptoms. CONCLUSIONS: Even though topographic
      dermatology is a somewhat reductive vision of skin diseases, pathology of the
      eyelids deserves special mention because of its polymorphism as well as its
      diagnostic and/or therapeutic significance.

PMID- 16885901
TI  - [Tumors of the eyelids in the elderly].
AB  - The clinical aspect of tumors of the eyelids is polymorphous; however, the most
      frequent are benign tumors such as papillomas, basal cell carcinoma, squamous
      cell carcinoma, meibomian gland carcinoma, and melanomas. An important step in
      the management of the malignant types is to try to establish clear margins
      through histopathologic techniques: the Mohs technique, the rapid fixation
      technique, and the frozen section method are the most frequent technical tools
      used today. For the most malignant tumors such as malignant melanoma and Merkel
      cell tumor, lymph sentinel biopsy is a recent, valuable tool, but its benefit
      needs to be confirmed in large series.

PMID- 16885902
TI  - [Involutional entropion and ectropion].
AB  - Entropion and ectropion are very common among old people. These malpositions
      concern mostly the lower lids. Involutional entropion and ectropion have some
      pathophysiologic mechanisms in common: lower lid horizontal laxity and lid
      retractor detachment. However, orbicularis muscle hypertrophy occurs only in
      entropion, and excess of posterior lamella has to be considered in ectropion.
      Clinical examination will guide surgical treatment. The authors present the main
      surgical procedures according to clinical findings. The goal is to prevent
      recurrence.

PMID- 16885903
TI  - [Involutional ptosis].
AB  - Aponeurotic defects and disinsertion of the levator aponeurosis are responsible
      for acquired involutional ptosis. The typical clinical findings in aponeurotic
      defects are high or moderate ptosis, good to excellent levator function, thinning
      of the eyelid above the tarsus, high to absent lid crease, and normal Muller's
      muscle function. The purpose of the treatment is to repair the defect or to
      advance the aponeurosis on the tarsus. This surgery can be done via the anterior
      approach with aponeurotic surgery or via the posterior approach with Muller's
      muscle conjunctival resection. In all cases, upper lid blepharoplasty is down.

PMID- 16885906
TI  - [Antitumor and chemopreventive activity of lactoferrin].
AB  - Lactoferrin, an evolutionarily old protein of the transferrin family, is among
      the proteins constituting the system of innate immunity; its action, however,
      also extends to the regulation of acquired immunity and other immunological
      phenomena. The actions of LF, confirmed in numerous in vitro and in vivo models,
      include participation in iron homeostasis, immunoregulatory properties, anti
      inflammatory, anti-tumor, and analgesic actions, regulation of bone metabolism,
      participation in embryonic development, reproductive functions, and others. LF
      plays an important role in the normal development of a newborn. The anti-tumor
      properties of LF were discovered about a decade ago and have been confirmed in
      many laboratory, preclinical, and clinical studies. The immunomodulatory
      properties of LF play a major role in its anti-tumor actions. Such actions of LF
      appeared particularly effective in cancer patients with impaired immunity. The
      growth of tumors is facilitated by low expressions of MHC and co-stimulatory
      antigens on tumor cells and the induction of suppressor cells and other
      inhibitory products by tumors. Enhancement of an anti-tumor immunological
      response may, therefore, restrict tumor growth. Studies showed that LF elevates
      the number and increases the activity of T and B lymphocytes and NK cells,
      stimulates the release of a number of cytokines (IL-1, -6, -8, -18, IFN-gamma,
      TNF alpha), increases phagocytic activity and cytotoxicity of
      monocytes/macrophages, accelerates the maturation of T and B cells, and elevates
      the expression of several types of cellular receptors, such as CD4, zeta chain of
      the CD3 complex, LFA-1, CD11, ICAM-1, and selectin P. Apart from its
      immunomodulatory properties, LF exhibits direct anti-tumor actions, such as
      lytic, pro-apoptotic, anti-proliferative, anti-angiogenic, anti-oxidant activity
      and the chelation of iron ions. LF also possesses chemo-preventive properties,
      regulates the activity of phase I and II enzymes participating in the activation
      and detoxification of carcinogens, and regulates the composition of the
      intestinal microflora. In this way it prevents the generation of tumors and their
      development at early stages of carcinogenesis.

PMID- 16885907
TI  - [Glycosaminoglycans in the pathogenesis and diagnostics of Graves's
      ophthalmopathy].
AB  - Graves's ophthalmopathy is an extrathyroidal tissue-specific symptom of Graves's
      disease characterized by inflammatory infiltration of orbital tissues. In several
      percent of patients the course of disease is severe, leading to serious ocular
      complications and affecting quality of life. Progress made in understanding the
      pathogenesis of GO has not been followed by better outcome of treatment and it is
      still one of the most complex problems of clinical endocrinology. In this
      respect, qualification for immunosuppressive treatment based on an assessment of
      the disease activity is a matter of great importance. Glycosaminogycans are
      linear, unbranched heteropolysaccharides built of repeating disaccharide
      sequences. These compounds are essential for the organization and function of
      connective tissue. Moreover, they also take part in the initiation and regulation
      of immune reactions. In this paper, glycosaminogycans are described with regard
      to their structure, metabolism, and function, with special emphasis on the tissue
      specificity of the orbit. Data concerning GAG useful in the management of
      patients with GO are highlighted.

PMID- 16885908
TI  - [Experimental and selected clinical aspects of active immunotherapy in leukemia].
AB  - The aim of the review is to summarize current knowledge concerning active
      immunotherapy in leukemia. The molecular mechanisms and selected clinical
      implications of different cancer vaccines used in pediatric and adult leukemias
      are discussed. Escape of neoplasmatic cells from elimination by host cells can be
      caused by immunological disturbances, such as the production of immunosuppressive
      cytokines and downregulation of costimulatory and adhesion molecules. Cells of
      acute lymphoblastic leukemia and chronic lymphocytic leukemia can be induced into
      antigen-presenting cells with the CD40 ligation system. After CD40 stimulation,
      leukemic cells achieve the phenotypic and functional characteristics of dendritic
      cells. In many studies it was confimed that these cells stimulate auto- and/or
      allogeneic T-cell response. Immunological response can be of cellular and humoral
      origin and is extensively examined. Similar effects using different cytokines
      such as GM-CSF, TNF-alpha, and IL-4 can be observed in acute myeloid leukemia and
      myelodysplastic syndromes. Clinical experience with such vaccines is limited, but
      the results of some preliminary reports are quite promising. Cancer vaccines are
      safe, result in host response, and probably prolong patients survival.

PMID- 16885909
TI  - [PEDF: an endogenous factor displaying potent neuroprotective, neurotrophic, and
      antiangiogenic activity].
AB  - PEDF (pigment epithelium-derived factor) was first purified in 1989 from the
      conditioned medium of human retinal pigment epithelial cells as a factor with
      potent differentiating activity in human retinoblastoma cells. This discovery
      triggered intensive research directed at elucidating the biological activity of
      this new factor. The presence of PEDF was confirmed in several structures of the
      eye and other organs (i.e. liver, lung, kidney) in both prenatal and postnatal
      life, and in almost all parts of the central nervous system. The synthesis and
      secretion of PEDF is more effective in young cells and decreases during their
      aging. Although many findings suggest a receptoric nature of PEDF action, the
      receptor responsible for its neuroprotective, neurotrophic, and antiangiogenic
      effect still remains to be identified. PEDF is capable of regulating many
      physiological processes; for example, it stimulates the differentiation of human
      retinoblastoma cells to neurons and increases the growth and survival of
      photoreceptor cells of the retina and neurons of the central and peripheral
      nervous system. Furthermore, this factor also protects immature neuron cells from
      apoptosis. PEDF, probably the most potent endogenous inhibitor of angiogenesis,
      behaves as a functional antagonist of vascular endothelial growth factor (VEGF)
      and inhibits neovascularization. Endowed with neuroprotective, neurotrophic, and
      antiangiogenic potential, PEDF itself, or its biologically active fragment, is
      currently considered an agent of great interest in the future therapy of an array
      of neurological, ophthalmological, and oncological disorders.

PMID- 16885911
TI  - The role of prevalence in the diagnosis of prostate cancer.
AB  - BACKGROUND: The worldwide incidence of prostate cancer has been rising rapidly,
      likely due to intensified effort in early detection and screening. Intense effort
      is also directed at novel schemas of chemoprevention and therapy. Incidence data
      are insufficient to identify the true magnitude of prostate cancer in a given
      population. The true prevalence of prostate cancer must be identified. METHODS:
      We reviewed the latest worldwide epidemiologic data and clinical studies on
      prostate cancer studying the true prevalence of this disease. RESULTS: The
      incidence of prostate cancer is increasing worldwide, with strong variation among
      regions. Prevalence studies based on autopsy data have confirmed a high frequency
      of latent prostate cancer in men of all ages. More aggressive screening measures
      using a lower prostate-specific antigen (PSA) threshold, together with an
      increasing number of biopsies, have escalated the detection of these latent
      cancers. CONCLUSIONS: Recent improvements in prostate cancer detection narrow the
      gap between the incidence and true prevalence of prostate cancer. This, however,
      raises concerns about the risk of over detection of latent cancers and thus
      identifying a need for improvement in screening strategies to better identify
      clinically significant disease.

PMID- 16885912
TI  - Laparoscopic surgery in urologic oncology.
AB  - BACKGROUND: Techniques in genitourinary oncologic surgery have evolved over the
      past several years, shifting from traditional open approaches toward minimally
      invasive routes by laparoscopy. METHODS: We reviewed the literature on
      laparoscopic surgery for genitourinary cancer, with emphasis on contemporary
      indications, complications, and oncologic outcome of laparoscopic surgery for
      urologic malignancies. RESULTS: All urologic oncology procedures have been
      performed laparoscopically. Laparoscopic radical nephrectomy is becoming the
      preferred approach for managing kidney cancer. The initial experience with
      nephroureterectomy is encouraging. Laparoscopic radical prostatectomy is rapidly
      becoming the standard in Europe and is the procedure of choice in many centers in
      the United States. CONCLUSIONS: When following the open oncologic principles for
      the surgical treatment of malignancies, laparoscopy offers similar oncologic
      clinical outcomes, less morbidity, improved operative precision, and reduced
      convalescence time.

PMID- 16885914
TI  - The role of external-beam radiation therapy in the treatment of clinically
      localized prostate cancer.
AB  - BACKGROUND: The treatment of clinically localized prostate cancer is
      controversial. Options include radical prostatectomy, external-beam radiation
      therapy (EBRT), brachytherapy, cryotherapy, and watchful waiting. METHODS: The
      author reviews EBRT as treatment for clinically localized prostate cancer, with
      particular emphasis on the technological advances that have allowed dose
      escalation and fewer therapy-related side effects. RESULTS: Technological
      advances in the last two decades have significantly improved the delivery of EBRT
      to the prostate. This has resulted in an overall increase in the total dose that
      can be safely delivered to the prostate, which has led to modest improvements in
      biochemical outcome. An alternative approach of combining androgen suppression
      therapy and EBRT has also been successful in improving clinical outcomes.
      However, establishing the optimal therapy for prostate cancer remains
      controversial. CONCLUSIONS: Recent progress has led to improvements in clinical
      outcomes in patients treated with EBRT for prostate cancer. It is hoped that the
      next decades will bring continued advances in the development of biologicals that
      will further improve current clinical outcomes.

PMID- 16885913
TI  - Sexual function after surgery for prostate or bladder cancer.
AB  - BACKGROUND: Compromised sexual function is often a side effect for patients
      following radical surgical procedures for bladder or prostate cancer. METHODS:
      The authors review the classification and physiology of sexual function and
      dysfunction. Moreover, they explain the possible pathophysiology directly
      resulting from surgery, and they discuss several approaches available to address
      these problems. RESULTS: Options for male sexual dysfunction, primarily erectile
      dysfunction resulting from radical prostatectomy or surgery for bladder cancer,
      range from patient education to penile prosthesis implantation. Female sexual
      dysfunction caused by surgical intervention for bladder cancer includes problems
      with libido, arousal, orgasm, and dyspareunia. Treatment options for women can
      include sex therapy, hormonal therapy, and preventive strategies. However, no
      consensus has been established on the most effective agents and time points to
      treat male or female sexual dysfunction following radical cystectomies or
      prostatectomies. The chronic intermittent treatment of erectile dysfunction
      following radical prostatectomy has been commonly referred to as penile
      rehabilitation. CONCLUSIONS: Additional research is needed to obtain further data
      concerning sexual dysfunction in both men and women following radical pelvic
      surgeries. Modification of surgical techniques, the use of various treatment
      modalities for sexual dysfunction, and the development of new agents will help to
      successfully minimize or prevent damage and restore normal sexual function after
      local surgical therapy for prostate or bladder cancer in the future.

PMID- 16885915
TI  - Novel agents and targets in managing patients with metastatic prostate cancer.
AB  - BACKGROUND: Docetaxel has recently been found to improve survival in patients
      with metastatic androgen-independent prostate cancer (AIPC). Chemotherapy as a
      first-line option leaves room for improvement, while second-line options are
      multiple and somewhat controversial. METHODS: Clinically relevant articles
      focusing on chemotherapy drugs for metastatic prostate cancer and their mechanism
      of action and efficacy were reviewed from January 2004 through April 2006.
      RESULTS: Docetaxel is the standard of care for AIPC. However, for doublets with
      docetaxel or second-line chemotherapy, multiple studies have shown interesting
      and promising results with calcitriol, thalidomide, bevacizumab, satraplatin,
      vaccines, ixabepilone, and atrasentan. CONCLUSIONS: Docetaxel should be
      considered for first-line treatment of metastatic AIPC. Due to its progression
      free survival of only 6 months, more effective drugs and drug combinations need
      to be developed to treat patients with AIPC. Combination treatments with
      docetaxel and other new agents are promising, but adequately powered phase III
      trials need to be conducted with survival as the principal endpoint for these
      promising drug combinations.

PMID- 16885916
TI  - Management of locally advanced renal cell carcinoma.
AB  - BACKGROUND: Renal cell carcinoma accounts for approximately 3% of adult
      malignancies and over 90% of primary renal tumors. Recurrence rates for patients
      with locally advanced renal cell carcinoma (LARCC) remain high. METHODS: The
      authors review literature regarding prognostic factors, potential biomarkers,
      surgical strategies, and adjuvant therapy trials for patients with LARCC.
      RESULTS: Molecular tumor markers may improve existing staging systems for
      predicting prognosis. Surgery is the best initial treatment for most patients
      with clinically localized renal tumors, although complete surgical resection can
      be challenging for patients with large tumors, bulky regional lymph node
      involvement, or inferior vena cava tumor thrombus. Significant recurrence rates
      for patients with LARCC undergoing nephrectomy indicate the presence of
      undetected micrometastases at the time of surgery. Adjuvant radiation,
      chemotherapy, and immunotherapy have been ineffective. Other trials of adjuvant
      therapy are ongoing. CONCLUSIONS: Aggressive surgical resection alone for LARCC
      is not sufficient to prevent disease recurrence in a significant number of
      patients. Adjuvant therapies are needed to improve cancer-specific survival.

PMID- 16885917
TI  - Overall and progression-free survival in metastatic melanoma: analysis of a
      single-institution database.
AB  - BACKGROUND: Many new agents are currently in trial in melanoma. It remains
      unclear, however, what the benefit of a given therapy may be since information on
      progression-free and overall survival of untreated patients is limited. Since few
      trials in melanoma have had a non-treated cohort, it remains unclear what
      survival can be expected in patients who are not treated with chemotherapy.
      METHODS: To help develop parameters for future trials, we analyzed treatment
      history and survival in 212 patients with metastatic melanoma seen at our
      institution between January 1998 and September 2003. A retrospective analysis was
      done using a database created for melanoma patients at our center. Patient
      survival information was determined from this database, tumor registry, Social
      Security index, and direct patient calls. Patient staging information was
      determined according to the 2001 guidelines. Non-chemotherapy-treated patients
      with M1c disease were used as "controls." RESULTS: The median survival of stage
      M1c melanoma was 6.0 months. Survival was longer for stage M1a and M1b and
      shorter in older patients. No significant differences were found in survival
      based on gender. Among chemotherapy-treated patients, those with progressive
      disease on treatment or with increased lactate dehydrogenase (LDH) fared worse
      than those with a clinical response or normal LDH, respectively. Patients treated
      with either biochemotherapy or temozolomide and thalidomide survived longer than
      those who received no chemotherapy treatment. Dacarbazine (DTIC) treatment did
      not prolong survival. CONCLUSIONS: In this retrospective review of patients
      treated at a single institution, those treated with multiagent chemotherapy but
      not with single-agent DTIC appeared to have had a survival benefit.

PMID- 16885918
TI  - Survival after surgical resection of isolated pulmonary metastases from malignant
      melanoma.
AB  - BACKGROUND: The overall prognosis for patients with metastatic malignant melanoma
      remains poor. However, careful staging and identification of patients with
      limited metastatic disease offers the opportunity for surgical salvage and
      improved survival for selected patients. METHODS: We reviewed the experience over
      the last 17 years at our institute with isolated pulmonary metastasectomy in 86
      patients with advanced malignant melanoma. RESULTS: Our data demonstrate an
      overall median time to relapse of approximately 8.4 months and a median survival
      of 35 months. The 5-year survival rate is estimated at 33%, and 16% remain
      continuously free of disease after a median follow-up of 35 months. Resection of
      properly staged and evaluated patients with limited pulmonary metastases appears
      to convey a significant survival benefit. Patients with a single metastasis fare
      best. CONCLUSIONS: These encouraging results offer a rationale for the careful
      follow-up of resected patients. One third of all relapses will be limited and
      additional surgery contributes to their overall survival.

PMID- 16885919
TI  - Misperceptions of medical understanding in low-literacy patients: implications
      for cancer prevention.
AB  - BACKGROUND: Patients with limited literacy skills often have difficulty
      understanding medical information, are less likely to undergo cancer screening,
      and present with cancer at later stages than patients with better literacy
      skills. Since primary care physicians are responsible for performing or
      initiating the majority of cancer screening in the United States, they need to be
      able to not only identify patients who might not understand medical information
      but also communicate effectively with them about cancer prevention and screening.
      METHODS: To determine whether family medicine residents could identify patients
      who might have difficulty understanding medical information because of limited
      literacy, we measured the literacy skills of patients in a university-based
      family medicine clinic using the short form of the Test of Functional Health
      Literacy in Adults (S-TOFHLA). After the patients completed their office visits
      with a physician, we asked family medicine residents to rate the patients'
      ability to understand medical information. RESULTS: Among 140 patients who met
      with 18 family medicine resident physicians, 24% had limited literacy skills
      based on testing with the S-TOFHLA. Residents identified only about half of these
      patients as having poor or below average understanding of medical information.
      CONCLUSIONS: IN many cases, family medicine residents are unable to identify
      patients who, based on assessment of their literacy skills, are likely to have
      difficulty understanding medical information. When working with residents,
      medical educators should promote the habit of taking poor literacy into account
      when communicating with patients.

PMID- 16885920
TI  - Challenges in community-based participatory research implementation: experiences
      in cancer prevention with Pacific Northwest American Indian tribes.
AB  - BACKGROUND: Much has been written about community-based participatory research
      (CBPR) history and principles, but few have addressed challenges in
      implementation in transcultural situations. The goal of this discussion is to
      address CBPR implementation issues in cancer prevention research with American
      Indian tribal communities in the Pacific Northwest. METHOD: Information in this
      discussion is drawn from qualitative research conducted over a 10-year period in
      which CBPR was employed in cancer prevention research with Pacific Northwest
      Indian tribes. CBPR principles provide the framework for the discussion:
      establishing trusting relationships, assuring participation, sharing power, and
      communicating. RESULTS: In this work, we found that CBPR is appropriate for use
      in Pacific Northwest Indian tribal communities and is compatible with cultural
      values. We also found that there are many challenges. Recommendations are
      provided on needed institutional and structural changes. CONCLUSIONS: CBPR is an
      important research approach in addressing cancer prevention health disparities
      among American Indian tribal communities. Continued effort needs to be directed
      toward creating systems and structures to support researchers in utilizing this
      method. Findings are of value to researchers aiming to implement CBPR in Indian
      communities and to practitioners, policy makers, and administrators who make
      decisions about CBPR funding and support structures.

PMID- 16885922
TI  - Analysis of variants in the complement factor H, the elongation of very long
      chain fatty acids-like 4 and the hemicentin 1 genes of age-related macular
      degeneration in the Finnish population.
AB  - PURPOSE: A strong association of a Tyr402His polymorphism in the complement
      factor H (CFH) gene and a Met299Val polymorphism in the elongation of very long
      chain fatty acids-like 4 (ELOVL4) gene with age-related macular degeneration
      (AMD) has been identified in Caucasian populations in the United States. Earlier
      a Gln5345Arg variant in the hemicentin 1 (HMCN1) gene was reported in a large AMD
      family in the United States. We wanted to investigate whether the polymorphisms
      of the CFH and the ELOVL4 genes or the mutation of the HMCN1 gene are associated
      with AMD in patients originating from the Finnish population with characteristics
      of a genetic isolate. METHODS: The material consisted of familial (n=181) and
      sporadic cases (n=154) with AMD, a control group with no AMD (non-AMD controls,
      n=105), and a control group of anonymous blood donors (blood donor controls, n
      =350). The DNA of the subjects was sequenced to analyze the variants of the three
      genes. RESULTS: We detected a strong association between the C/C-genotype
      compared to the T/T-genotype of Tyr402His polymorphism (first base of the Tyr
      codon changes) of the CFH gene and AMD in the AMD cases compared to the non-AMD
      (p=8.86x10(-12)) or to blood donor controls (p=2.02x10(-13)). The frequency of
      the C/C genotype was significantly increased in both familial cases compared to
      non-AMD controls with non-adjusted odds ratio (OR) 10.1 (confidence intervals
      [CI] 95% 4.64-22.2) or compared to blood donor controls with non-adjusted OR 5.50
      (CI 95% 3.17-9.55) and in sporadic cases with non-adjusted OR 9.33 (CI 95% 4.10
      21.3; non-AMD-controls), OR 5.06 (CI 95% 2.75-9.28; blood donor controls).
      Frequency of C allele differed significantly between cases and controls
      (p=1.32x10(-11); non-AMD-controls and p=3.94x10(-14); blood donor controls). No
      association with AMD was detected with Met299Val polymorphism in the ELOVL4 gene
      in the familial or sporadic cases compared to non-AMD or blood donor controls.
      None of our subjects (258 AMD cases, 72 non-AMD controls) had the Gln5345Arg
      variant in the HMCN1 gene. CONCLUSIONS: The CFH gene polymorphism seems to be an
      important etiologic factor for AMD also in the isolated Finnish population.

PMID- 16885921
TI  - A novel mutation in the connexin 46 gene (GJA3) causes autosomal dominant zonular
      pulverulent cataract in a Hispanic family.
AB  - PURPOSE: A five-generation Hispanic pedigree with autosomal dominant zonular
      pulverulent cataract was studied to identify the causative mutation in connexin
      46 (Cx46), a gap junction protein responsible for maintaining lens homeostasis.
      METHODS: Twenty-six individuals from the family were comprehensively clinically
      examined. DNA was extracted from their peripheral blood samples. The DNA was used
      for automated genotyping with fluorescently labeled microsatellite markers and
      for mutation detection by automated sequencing. RESULTS: A novel D3Y missense
      mutation in GJA3 segregated with autosomal dominant (AD) zonular pulverulent
      cataract throughout the family. The mutation was absent in the unaffected
      individuals in the family and in 230 control chromosomes. CONCLUSIONS: A novel
      mutation causing AD zonular pulverulent cataract has been identified in a
      Hispanic Central American family. This is the first report of a mutation in GJA3
      causing autosomal dominant congenital cataract (ADCC) in this ethnic group. It is
      also the first reported cataract-causing mutation in the NH2-terminal region of
      the Cx46 protein.

PMID- 16885923
TI  - Transpupillary thermotherapy-induced modification of angiogenesis- and
      coagulation-related gene expression in the rat posterior fundus.
AB  - PURPOSE: To study gene expression changes in the rat retina and choroid following
      transpupillary thermotherapy (TTT) and to identify molecular mechanisms that may
      enhance treatment of choroidal neovascularization, complicating age-related
      macular degeneration. METHODS: One fundus of Brown Norway rats was treated with
      an 810 nm diode laser while the contralateral fundus received no treatment. The
      mRNA was extracted and processed for cDNA microarray analysis. Genes with
      increased expression were validated by semiquantitative reverse transcription
      polymerase chain reaction (PCR) and quantitative real-time PCR (qRT-PCR).
      RESULTS: Of the 14,815 cDNA elements on the array, 12 genes were up-regulated in
      TTT treated eyes. Upregulation of eight of these 12 genes could be verified by
      semiquantitative RT-PCR. The eight verified genes were EPCR, IL-1beta, MCP-1, TSP
      1, Fgl, Asns, MT-2, and NMDMC, which included 4 angiogenesis- and coagulation
      related genes. CONCLUSIONS: This study demonstrates upregulation of angiogenesis-
      and coagulation-related genes following TTT. The response profile and its
      temporal relationships provide insight into the molecular mechanisms that lead to
      vascular occlusion and antiangiogenesis induced by TTT.

PMID- 16885924
TI  - Peripherin/RDS and VMD2 mutations in macular dystrophies with adult-onset
      vitelliform lesion.
AB  - PURPOSE: Adult-onset vitelliform macular dystrophy (AVMD) is a pleomorphic late
      onset macular phenotype characterized by a central yellow deposit between the
      neural retina and retinal pigment epithelium. Mutations in the genes encoding
      peripherin/RDS and VMD2 have been previously reported in some subjects with AVMD.
      The purpose of this investigation was to determine the prevalence of mutations in
      these two genes in a cohort of cases with macular dystrophies presenting with
      vitelliform lesions in adulthood. METHODS: Fifty nine consecutively ascertained
      and unrelated subjects prospectively coded as pattern or vitelliform macular
      dystrophies were reviewed and twelve subjects with a vitelliform lesion were
      identified. Patient evaluation included comprehensive ocular examination, retinal
      imaging, and functional studies in selected subjects. The RDS and VMD2 genes were
      screened for variation by direct DNA sequencing of coding regions and intron/exon
      boundaries. RESULTS: Twenty-two DNA sequence variants were identified in the
      genes encoding RDS and VMD2. A Pro210Arg variant found in the RDS gene of one
      subject was the only definite mutation detected in either gene. CONCLUSIONS: The
      Pro210Arg mutation has been reported previously in patients with pattern
      dystrophy confirming the observation that pattern dystrophy can present with an
      AVMD phenotype. Although RDS and VMD2 are the only known genes with mutations
      contributing to AVMD, our series demonstrates that most patients have mutations
      in genes that have yet to be discovered.

PMID- 16885925
TI  - OPTN gene: profile of patients with glaucoma from India.
AB  - PURPOSE: Optineurin gene (OPTN) mutations are reported in primary open angle
      glaucoma patients (POAG) from different populations. The coding and noncoding
      regions of OPTN were screened for mutations in 100 Indian high tension glaucoma
      patients (HTG). The frequency of the OPTN M98K mutation in an additional 120
      patients (70 HTG and 50 normal tension glaucoma [NTG]) was analyzed by
      restriction enzyme digestion. METHODS: The HTG patients (about 40 years of age)
      were characterized by open angles on gonioscopy, with raised intraocular pressure
      (IOP) more than 21 mmHg (<21 mmHg on office diurnal phasing for NTG), and typical
      glaucomatous disc changes with corresponding visual field defects in the absence
      of any secondary cause. One hundred HTG patients and controls were screened for
      OPTN mutations by direct sequencing using an ABI prism 310/3100 Avant genetic
      analyzer. The M98K status was analyzed by restriction enzyme digestion with StuI.
      A genotype/phenotype correlation was also attempted for OPTN sequence alterations
      with clinical parameters such as age at diagnosis, intraocular pressure, cup:disc
      ratio, etc. The putative change in the transcription factor binding site for the
      IVS7 +24G>A polymorphism was attempted with AliBaba software (version 2.1).
      RESULTS: Six sequence alterations were observed in the 100 POAG patients by
      direct sequencing. The M98K substitution was observed in a total of 10 patients
      (7/170 HTG and 3/50 NTG) contributing to 4.1% in HTG and 6% in the NTG group and
      not in the controls. The IVS7+24G>A nucleotide change showed a significant
      difference in the HTG group (7/100) when compared to the control group (0/100)
      and found to be associated with increased IOP at diagnosis (p=0.03). The
      IVS7+24G>A polymorphism resulted in the creation of binding sites for
      transcription factors NF-1 and CPE that were not present in the wild type.
      CONCLUSIONS: The current study suggests a possible role of SNPs rather than
      mutations in OPTN in POAG pathology in the Indian population.

PMID- 16885926
TI  - Nutritional hormesis.
AB  - OBJECTIVE: Hormesis, the biological and toxicological concept that small
      quantities have opposite effects from large quantities, is reviewed with emphasis
      on its relevance to nutrition. RESULTS: Hormetic and other dose-response
      relationships are categorized, depicted, and discussed. Evidence for nutritional
      hormesis is presented for essential vitamin and mineral nutrients, dietary
      restriction, alcohol (ethanol), natural dietary and some synthetic pesticides,
      some herbicides, and acrylamide. Some of the different hormetic mechanisms that
      have been proposed are reviewed. CONCLUSIONS: The credence and relevance of
      hormesis to nutrition are considered to be established. The roles of hormesis in
      nutritional research and in formulating nutritional guidelines are discussed.
      SPONSORSHIP: The New York City Department of Health and Mental Hygiene.

PMID- 16885927
TI  - Impact of national fortification of fluid milks and margarines with vitamin D on
      dietary intake and serum 25-hydroxyvitamin D concentration in 4-year-old
      children.
AB  - OBJECTIVE: To assess the impact of national fortification of fluid milks and
      margarines with vitamin D on dietary intake and on serum 25-hydroxyvitamin D
      concentration in Finnish 4-year-old children. DESIGN, SUBJECTS AND METHODS: Two
      cohorts of children were studied during wintertime, one before (n=82) in 2001
      2002 and the other after (n=36) the initiation of fortification in 2003-2004.
      Dietary intake was estimated by 4-day food records and serum 25-hydroxyvitamin D
      concentration was analyzed by radioimmunoassay. RESULTS: The mean intake of
      vitamin D was higher the after initiation of fortification (mean (95% confidence
      interval (CI)); 4.5 (3.8-5.1) microg) than before it (2.1 (95% CI 1.8-2.3)
      microg; P<0.001), although there were no differences in consumption of the main
      food sources of vitamin D between the two cohorts. The difference between the
      cohorts was also evident when the intake of vitamin D was adjusted for energy
      intake (0.78 (95% CI 0.70-0.90) and 0.37 (95% CI 0.32-0.42) microg/MJ after and
      before fortification, respectively, P<0.001). After fortification, the mean
      intake approached that recommended, but was achieved by only 30.6% of the
      children. Equally, the serum 25-hydroxyvitamin D concentration was higher after
      fortification (64.9 (95% CI 59.7-70.1) nmol/l) compared to prior it (54.7 (95% CI
      51.0-58.4) nmol/l; P=0.002). CONCLUSIONS: The results indicate that the national
      fortification of fluid milks and margarines with vitamin D safely improved the
      vitamin D status of children. This approach, in view of the novel health effects
      beyond bone metabolism, encourages fortification of new food sources with vitamin
      D or use of vitamin D supplements particularly during wintertime.

PMID- 16885928
TI  - Pattern of dietary fiber intake among the Japanese general population.
AB  - OBJECTIVES: To evaluate the dietary fiber (DF) intake pattern among the Japanese
      general population. DESIGN: We performed a dietary survey among the general
      population in northern Japan to evaluate the intake patterns. DF intake was
      calculated by substituting the DF content of each food in the Dietary Fiber Table
      for the intake of each food from this dietary survey. SUBJECTS: Five hundred and
      seventy-seven subjects participated in the study, 198 men and 379 women. RESULTS:
      In subjects with higher DF intakes the origins of the DF that were from all food
      groups, but with the notable exception of rice. The contribution of the seaweed
      group was of particular interest. From multiple regression analysis, as for food
      group, seaweeds showed the highest positive correlation with DF intake in both
      genders, followed by vegetables, pulses, fruits. On the other hand, rice showed
      the negative correlation with DF intake in both genders. As for life factor, body
      mass index showed the negative correlation with DF intake in women. CONCLUSION:
      Seaweed, a typical Japanese food, was most related to the increase in DF intake
      for the Japanese general population, whereas rice, the Japanese staple, had a
      small influence on decreased DF intake.

PMID- 16885930
TI  - Dietary intake in asylum seeker children in The Netherlands, strongly related to
      age and origin.
AB  - OBJECTIVE: To monitor the dietary intake of energy, macro- and micronutrients in
      asylum seeker children. DESIGN AND SETTING: Cross-sectional study in three asylum
      seeker centres in The Netherlands. SUBJECTS: Hundred and sixteen children 2-12
      years old (86% of the study cohort) provided a dietary history. METHOD: The
      dietary intake was estimated by 24 h recall, and the origin of the children was
      classified in three geographic regions: African (n=45), Central Asia (n=34) or
      Eastern Europe (n=37). RESULTS: The total energy intake from fat was in 24% of
      the children above 40En%. Seventy per cent of the children above 4 year of age
      had a saturated fat intake above 10En%. The children from Eastern Europe had a
      higher intake of fat and disaccharides than the children from the other regions.
      Among the children, an intake less than 80% of the recommended daily allowances
      of micronutrients was found for calcium (42%), iron (49%), vitamin A (45%) and
      vitamin D (80%). An inadequate dietary intake of iron and vitamin D was
      significantly more seen among the youngest children, whereas an inadequate intake
      of calcium and vitamin A was found more among the elder children. CONCLUSIONS:
      The dietary intake of a prominent proportion of these children contains too much
      fat and insufficient amounts of calcium, iron, vitamin A and vitamin D. The low
      micronutrient intake of the asylum seeker children can be considered as a
      nutritional risk. Nutritional education and strategies to improve the macro- and
      micronutrient intake of asylum seeker children is indicated.

PMID- 16885931
TI  - Sodium iron (III) ethylenediaminetetraacetic acid synthesis to reduce iron
      deficiency globally.
AB  - Despite major interest in sodium iron (III) ethylenediaminetetraacetic acid's
      (EDTA) potential use in food fortification programs in potentially curbing the
      global problem of iron deficiency and its anemia, synthesis methods of stable
      isotope-labeled sodium iron (III) EDTA for use in human bioavailability studies
      are incomplete, incorrect or totally lacking. Owing to a number of clinical
      research groups requiring this compound in bioavailability studies, in both
      developing and already developed countries, we simplified and optimized the
      synthesis of sodium iron (III) EDTA from a block of isotopically enriched iron
      metal, in order that it be easily reproduced, cheaply, using simple basic
      laboratory apparatus. The resulting product is of high purity (>99.0%), and may
      be used for human stable isotope bioavailability studies. The simplicity of this
      method allows for the many research groups, currently doing such studies, to
      perform their own syntheses. Additionally, more uniformity in this synthesis will
      reduce the variation observed between such studies.

PMID- 16885929
TI  - Relationship between the surrogate anthropometric measures, foot length and chest
      circumference and birth weight among newborns of Sarlahi, Nepal.
AB  - BACKGROUND: Classification of infants into low birth weight (LBW, <2500 g) or
      very low birth weight (VLBW, <2000 g) categories is a crucial step in targeting
      interventions to high-risk infants. OBJECTIVE: To compare the validity of chest
      circumference and foot length as surrogate anthropometric measures for the
      identification of LBW and VLBW infants. SUBJECTS AND SETTING: Newborn infants
      (n=1640) born between March and June 2004 in 30 Village Development Committees of
      Sarlahi district, Nepal. DESIGN: Chest circumference, foot length and weight
      (SECA 727, precise to 2 g) of newborns were measured within 72 h after birth. The
      sensitivity, specificity and predictive values for a range of cutoff points of
      the anthropometric measures were estimated using the digital scale measurements
      as the gold standard. RESULTS: Among LBW infants (469/1640, 28.6%), chest
      circumference measures <30.3 cm were 91% sensitive and 83% specific. Similar
      levels of sensitivity for foot length were achieved only with considerable loss
      of specificity (<45%). Foot length measurements <6.9 cm were 88% sensitive and
      86% specific for the identification of VLBW infants. CONCLUSION: Chest
      circumference was superior to foot length in classification of infants into birth
      weight categories. For the identification of VLBW infants, foot length performed
      well, and may be preferable to chest circumference, as the former measure does
      not require removal of infant swaddling clothes. In the absence of more precise
      direct measures of birth weight, chest circumference is recommended over foot
      length for the identification of LBW infants.

PMID- 16885932
TI  - Folate intakes and folate biomarker profiles of pregnant Japanese women in the
      first trimester.
AB  - OBJECTIVE: To assess the status of dietary folate intake, serum and red blood
      cell (RBC) folate, and related nutritional biomarkers in healthy Japanese women
      in early pregnancy. DESIGN: A cross-sectional, observational study. SUBJECTS:
      Pregnant women in the first trimester, at 7-15 weeks gestation (n=70), who were
      not consuming any folate supplements or folate fortified foods. METHODS: Three
      day dietary records were obtained from each subject to assess dietary folate
      intake. Blood samples were collected for measurement of biomarkers. Biomarkers
      and nutrient intake were analyzed in two groups defined by their serum folate
      concentrations: the low folate group (serum folate < 9 ng/ml) and the high folate
      group (serum folate > or = 9 ng/ml). RESULT: Mean serum and RBC folate
      concentrations in all subjects were 10.3 and 519 ng/ml, respectively. These
      levels were remarkably higher than the reported values from many other countries
      despite our subjects receiving no folic acids supplements. However, mean folate
      intake by our subjects from natural foods was 289 microg/day, which is thought to
      be low according to the Japanese dietary recommendation specified for pregnant
      women. The intake of spinach and fruits was significantly greater in the high
      folate group than in the low folate group. CONCLUSION: Folate intake was thought
      to be adequate to maintain a desirable level of serum folate concentration in
      Japanese pregnant women in the first trimester, although the intake of folate
      from natural food was not high enough to meet the recommended daily intake.

PMID- 16885933
TI  - Long-term mortality in anorexia nervosa: a report after an 8-year follow-up and a
      review of the most recent literature.
AB  - OBJECTIVE: To evaluate long-term mortality rate of anorexia nervosa (AN) patients
      in a southern Italy population compared to the most recent literature. DESIGN:
      Retrospective and review setting. PATIENTS AND INTERVENTIONS: One hundred and
      forty-seven female AN patients, consecutively admitted from 1994 to 1997 to the
      Outpatient Unit, were re-examined between June and November 2003. Our data are
      compared with 10 other studies published since 1988. RESULTS: One hundred and
      twenty-three deaths in 2240 patients, amounting to a total mortality rate of
      5.25% were reported in the literature. Deaths due to suicide, AN-related and AN
      unrelated diseases were 1.20, 3.07 and 0.98%, respectively. After correcting for
      unrelated deaths, mortality rate was 4.27%. In our 8-year follow-up, we found a
      mortality rate of 2.72% (1.82% after correcting for unrelated deaths).
      Standardized mortality ratio was 9.7. CONCLUSION: We interpret our favourable
      findings as a consequence of an integrated, clinical-nutritional and psychiatric
      approach. Finally, considering AN demographic characteristics, that is young
      female subjects in Westernized societies, mortality rate is confirmed to be
      dramatically high.

PMID- 16885934
TI  - Nutritional determinants of plasma total homocysteine distribution in the Canary
      Islands.
AB  - OBJECTIVE: We sought to define plasma homocysteine reference values in healthy
      individuals in the Canary Islands and to determine its relations to folate and
      vitamin B12 intakes and concentrations. DESIGN: Cross-sectional study. SETTING:
      Population-based representative sample of 557 participants, aged 18-65 years,
      from the Canary Islands Nutrition Survey (ENCA). SUBJECTS: All participants
      completed two 24-h dietary recalls and a general questionnaire collecting socio
      demographic and health-related lifestyle information. INTERVENTIONS: Plasma
      homocysteine and serum vitamin B12 levels were measured by immunoassay, whereas
      folate levels through an automated ionic capturing method. RESULTS: Median plasma
      homocysteine was 11.9 micromol/l, higher in men (13.1 micromol/l) than in women
      (10.9 micromol/l) (P<0.001) and positively associated with age in both sexes
      (P<0.001). The prevalence of hyperhomocysteinaemia (> or = 15 micromol/l), 21.4%,
      was also greater in men (32.2%) than in women (13.4%). There were significant
      negative correlations between plasma homocysteine and serum (r=-0.32, P<0.001)
      and erythrocyte (r=-0.26, P<0.001) folate, as well as serum vitamin B12 (r=-0.28,
      P<0.001) concentrations. When divided in quartiles of vitamin intakes or
      concentrations, men with the lowest vitamin B12 and folate serum values had
      significantly higher plasma homocysteine concentrations than those in the other
      three quartiles. In women, hyperhomocysteinaemia was higher in the lowest
      quartiles of folate intake and serum and erythrocyte folate concentrations.
      CONCLUSIONS: These data provide further evidence that hyperhomocysteinaemia is a
      sensitive marker of inadequate folate and vitamin B12 status, allowing for the
      identification of those with greatest need for nutritional interventions.

PMID- 16885935
TI  - Prior exposure to chronic stress and MDMA potentiates mesoaccumbens dopamine
      release mediated by the 5-HT(1B) receptor.
AB  - (+) 3,4,-Methylenedioxymethamphetamine (MDMA) is an abused drug that acutely
      releases serotonin (5-HT) and dopamine (DA) but produces long-term damage to 5-HT
      terminals. MDMA-induced DA release has been shown to be dampened by 5-HT.
      Although stress also activates the mesolimbic DA pathway, it is unknown if
      chronic stress after exposure to neurotoxic doses of MDMA will augment MDMA
      induced DA release in the nucleus accumbens shell (NAcc(sh)). Rats were
      pretreated with MDMA (10 mg/kg x 4, intraperitoneal (i.p.)). After 7 days, rats
      were subjected to 10 days of chronic unpredictable stress. DA release in the
      NAcc(sh) and 5-HT in the ventral tegmental area (VTA) were measured after a
      challenge injection of MDMA (5 mg/kg, i.p.). The combination of pretreatment with
      MDMA+stress decreased basal concentrations of 5-HT in the VTA and DA in the
      NAcc(sh) and enhanced MDMA-stimulated DA release in the NAcc(sh). Pretreatment
      with MDMA or stress alone blunted MDMA-induced 5-HT release in the VTA. The
      augmentation of MDMA-induced DA release in rats pretreated with MDMA+chronic
      stress was attenuated by perfusion of the 5-HT(1B) antagonist, GR127935 into the
      VTA before the MDMA challenge injection. These results suggest that prior
      exposure to both MDMA and stress can produce a long-term augmentation in
      mesolimbic DA transmission and enhanced drug abuse vulnerability that is
      mediated, in part, by the 5-HT(1B) receptor in the VTA.

PMID- 16885936
TI  - Effects of short-term abstinence from escalating doses of D-amphetamine on drug
      and sucrose-evoked dopamine efflux in the rat nucleus accumbens.
AB  - Abstinence from high doses of psychostimulant drugs, in both humans and rodents,
      is linked to adverse psychological effects including anhedonia, a core symptom of
      major depression, manifested behaviorally as decreased responding for rewarding
      stimuli. The present study used brain microdialysis in freely moving rats to
      examine the effect of D-amphetamine (D-amph) withdrawal on changes in
      extracellular dopamine (DA) levels in the nucleus accumbens (NAc) evoked by D
      amph or behavior related to sucrose consumption. D-amph was administered
      intraperitoneally (i.p.) according to an escalating dose (ED) schedule (from 1 to
      10 mg/kg, 3 doses/day). We first confirmed the development of tolerance by
      monitoring DA efflux in the NAc in response to 5 and 10 mg/kg doses of D-amph
      administered during the ED schedule of drug administration and again in response
      to the 5 mg/kg dose of D-amph 72 h following the last 10 mg/kg D-amph injection.
      In a separate study, DA efflux in the NAc was first shown to be increased
      significantly during both preparatory and consummatory phases of responding for a
      4% sucrose solution. Withdrawal from the ED schedule of D-amph caused a selective
      attenuation of DA efflux only during the preparatory phase of the sucrose test.
      These results provided convincing evidence of neurochemical adaptation within the
      mesocorticolimbic DA pathway during and following the administration of an ED
      schedule of D-amph as well as suppressed neurochemical responses to a
      psychostimulant drug and cues associated with a natural reward after withdrawal
      from drug treatment. Accordingly, these findings support the hypothesis that
      downregulation of mesocorticolimbic DA function maintained during D-amph
      withdrawal may account for the selective disruption of motivated behavior
      reported in studies employing psychostimulant drug withdrawal as a model of
      depression in rodents.

PMID- 16885941
TI  - No more protection.

PMID- 16885937
TI  - In situ structure of the complete Treponema primitia flagellar motor.
AB  - The bacterial flagellar motor is an amazing nanomachine: built from approximately
      25 different proteins, it uses an electrochemical ion gradient to drive rotation
      at speeds of up to 300 Hz (refs 1, 2). The flagellar motor consists of a fixed,
      membrane-embedded, torque-generating stator and a typically bidirectional,
      spinning rotor that changes direction in response to chemotactic signals. Most
      structural analyses so far have targeted the purified rotor, and hence little is
      known about the stator and its interactions. Here we show, using electron
      cryotomography of whole cells, the in situ structure of the complete flagellar
      motor from the spirochaete Treponema primitia at 7 nm resolution. Twenty
      individual motor particles were computationally extracted from the
      reconstructions, aligned and then averaged. The stator assembly, revealed for the
      first time, possessed 16-fold symmetry and was connected directly to the rotor, C
      ring and a novel P-ring-like structure. The unusually large size of the motor
      suggested mechanisms for increasing torque and supported models wherein critical
      interactions occur atop the C ring, where our data suggest that both the carboxy
      terminal and middle domains of FliG are found.

PMID- 16885942
TI  - What's in a name?

PMID- 16885943
TI  - A foundation for Africa.

PMID- 16885946
TI  - Maths 'Nobel' rumoured for Russian recluse.

PMID- 16885945
TI  - Bird flu not set for pandemic, says US team.

PMID- 16885948
TI  - NASA threatens to axe science on space station.

PMID- 16885947
TI  - The proof is in the product.

PMID- 16885950
TI  - Singapore pulls plug on US collaboration.

PMID- 16885952
TI  - Meteorologists pour into west Africa.

PMID- 16885951
TI  - Mouse data hint at human pheromones.

PMID- 16885953
TI  - Home health tests are 'genetic horoscopes'.

PMID- 16885956
TI  - Gas for the greenhouse.

PMID- 16885957
TI  - Chemistry: what chemists want to know.

PMID- 16885958
TI  - Conservation at a distance: atomic detectives.

PMID- 16885959
TI  - Conservation at a distance: a gentle way to age.

PMID- 16885960
TI  - Holding the centre among the scatter-brained.

PMID- 16885961
TI  - Bias was built into research from the beginning.

PMID- 16885962
TI  - Let's encourage gentler, more reflective scientists.

PMID- 16885963
TI  - The gender debate: science promises an honest investigation of the world.

PMID- 16885968
TI  - Evolutionary biology: how to build a longer beak.

PMID- 16885969
TI  - Particle physics: a finer constant.

PMID- 16885972
TI  - Astronomy: a dwarf-eats-dwarf world.

PMID- 16885971
TI  - Chemical biology: cutting out the middle man.

PMID- 16885973
TI  - Energy technology: hydrogen quick and clean.

PMID- 16885974
TI  - Superconductivity: hot vibes.

PMID- 16885975
TI  - Behavioural ecology: bees associate warmth with floral colour.
AB  - Floral colour signals are used by pollinators as predictors of nutritional
      rewards, such as nectar. But as insect pollinators often need to invest energy to
      maintain their body temperature above the ambient temperature, floral heat might
      also be perceived as a reward. Here we show that bumblebees (Bombus terrestris)
      prefer to visit warmer flowers and that they can learn to use colour to predict
      floral temperature before landing. In what could be a widespread floral
      adaptation, plants may modulate their temperature to encourage pollinators to
      visit.

PMID- 16885976
TI  - Superhydrophobicity: drying transition of confined water.
AB  - Long-range hydrophobic interactions operating underwater are important in the
      mediation of many natural and synthetic phenomena, such as protein folding,
      adhesion and colloid stability. Here we show that rough hydrophobic surfaces can
      experience attractive forces over distances more than 30 times greater than any
      reported previously, owing to the spontaneous evaporation of the intervening,
      confined water. Our finding highlights the importance of surface roughness in the
      interaction of extended structures in water, which has so far been largely
      overlooked.

PMID- 16885978
TI  - The removal of cusps from galaxy centres by stellar feedback in the early
      Universe.
AB  - The standard cosmological model, now strongly constrained by direct observations
      of the Universe at early epochs, is very successful in describing the evolution
      of structure on large and intermediate scales. Unfortunately, serious
      contradictions remain on smaller, galactic scales. Among the main small-scale
      problems is a significant and persistent discrepancy between observations of
      nearby galaxies, which imply that galactic dark matter haloes have a density
      profile with a flat core, and the cosmological model, which predicts that the
      haloes should have divergent density (a cusp) at the centre. Here we report
      numerical simulations that show that random bulk motions of gas in small
      primordial galaxies, of the magnitude expected in these systems, will result in a
      flattening of the central dark matter cusp on relatively short timescales
      (approximately 10(8) years). Gas bulk motions in early galaxies are driven by
      supernova explosions that result from ongoing star formation. Our mechanism is
      general, and would have operated in all star-forming galaxies at redshifts z > or
      = 10. Once removed, the cusp cannot be reintroduced during the subsequent mergers
      involved in the build-up of larger galaxies. As a consequence, in the present
      Universe both small and large galaxies would have flat dark matter core density
      profiles, in agreement with observations.

PMID- 16885977
TI  - P2X receptors as cell-surface ATP sensors in health and disease.
AB  - P2X receptors are membrane ion channels activated by the binding of extracellular
      adenosine triphosphate (ATP). For years their functional significance was
      consigned to distant regions of the autonomic nervous system, but recent work
      indicates several further key roles, such as afferent signalling, chronic pain,
      and in autocrine loops of endothelial and epithelial cells. P2X receptors have a
      molecular architecture distinct from other ion channel protein families, and have
      several unique functional properties.

PMID- 16885979
TI  - Survival of a brown dwarf after engulfment by a red giant star.
AB  - Many sub-stellar companions (usually planets but also some brown dwarfs) orbit
      solar-type stars. These stars can engulf their sub-stellar companions when they
      become red giants. This interaction may explain several outstanding problems in
      astrophysics but it is unclear under what conditions a low mass companion will
      evaporate, survive the interaction unchanged or gain mass. Observational tests of
      models for this interaction have been hampered by a lack of positively identified
      remnants-that is, white dwarf stars with close, sub-stellar companions. The
      companion to the pre-white dwarf AA Doradus may be a brown dwarf, but the
      uncertain history of this star and the extreme luminosity difference between the
      components make it difficult to interpret the observations or to put strong
      constraints on the models. The magnetic white dwarf SDSS J121209.31 + 013627.7
      may have a close brown dwarf companion but little is known about this binary at
      present. Here we report the discovery of a brown dwarf in a short period orbit
      around a white dwarf. The properties of both stars in this binary can be directly
      observed and show that the brown dwarf was engulfed by a red giant but that this
      had little effect on it.

PMID- 16885980
TI  - Interplay of electron-lattice interactions and superconductivity in
      superconductivity in Bi2Sr2CaCu2O8+delta.
AB  - Formation of electron pairs is essential to superconductivity. For conventional
      superconductors, tunnelling spectroscopy has established that pairing is mediated
      by bosonic modes (phonons); a peak in the second derivative of tunnel current
      d2I/dV2 corresponds to each phonon mode. For high-transition-temperature (high
      T(c)) superconductivity, however, no boson mediating electron pairing has been
      identified. One explanation could be that electron pair formation and related
      electron-boson interactions are heterogeneous at the atomic scale and therefore
      challenging to characterize. However, with the latest advances in d2I/dV2
      spectroscopy using scanning tunnelling microscopy, it has become possible to
      study bosonic modes directly at the atomic scale. Here we report d2I/dV2 imaging
      studies of the high-T(c) superconductor Bi2Sr2CaCu2O8+delta. We find intense
      disorder of electron-boson interaction energies at the nanometre scale, along
      with the expected modulations in d2I/dV2 (refs 9, 10). Changing the density of
      holes has minimal effects on both the average mode energies and the modulations,
      indicating that the bosonic modes are unrelated to electronic or magnetic
      structure. Instead, the modes appear to be local lattice vibrations, as
      substitution of 18O for 16O throughout the material reduces the average mode
      energy by approximately 6 per cent--the expected effect of this isotope
      substitution on lattice vibration frequencies. Significantly, the mode energies
      are always spatially anticorrelated with the superconducting pairing-gap
      energies, suggesting an interplay between these lattice vibration modes and the
      superconductivity.

PMID- 16885981
TI  - Adaptive liquid microlenses activated by stimuli-responsive hydrogels.
AB  - Despite its compactness, the human eye can easily focus on different distances by
      adjusting the shape of its lens with the help of ciliary muscles. In contrast,
      traditional man-made optical systems achieve focusing by physical displacement of
      the lenses used. But in recent years, advances in miniaturization technology have
      led to optical systems that no longer require complicated mechanical systems to
      tune and adjust optical performance. These systems have found wide use in
      photonics, displays and biomedical systems. They are either based on arrays of
      microlenses with fixed focal lengths, or use external control to adjust the
      microlens focal length. An intriguing example is the tunable liquid lens, where
      electrowetting or external pressure manipulates the shape of a liquid droplet and
      thereby adjusts its optical properties. Here we demonstrate a liquid lens system
      that allows for autonomous focusing. The central component is a stimuli
      responsive hydrogel integrated into a microfluidic system and serving as the
      container for a liquid droplet, with the hydrogel simultaneously sensing the
      presence of stimuli and actuating adjustments to the shape--and hence focal
      length--of the droplet. By working at the micrometre scale where ionic diffusion
      and surface tension scale favourably, we can use pinned liquid-liquid interfaces
      to obtain stable devices and realize response times of ten to a few tens of
      seconds. The microlenses, which can have a focal length ranging from -infinity to
      +infinity (divergent and convergent), are also readily integrated into arrays
      that may find use in applications such as sensing, medical diagnostics and lab-on
      a-chip technologies.

PMID- 16885982
TI  - Plant litter decomposition in a semi-arid ecosystem controlled by
      photodegradation.
AB  - The carbon balance in terrestrial ecosystems is determined by the difference
      between inputs from primary production and the return of carbon to the atmosphere
      through decomposition of organic matter. Our understanding of the factors that
      control carbon turnover in water-limited ecosystems is limited, however, as
      studies of litter decomposition have shown contradictory results and only a
      modest correlation with precipitation. Here we evaluate the influence of solar
      radiation, soil biotic activity and soil resource availability on litter
      decomposition in the semi-arid Patagonian steppe using the results of
      manipulative experiments carried out under ambient conditions of rainfall and
      temperature. We show that intercepted solar radiation was the only factor that
      had a significant effect on the decomposition of organic matter, with attenuation
      of ultraviolet-B and total radiation causing a 33 and 60 per cent reduction in
      decomposition, respectively. We conclude that photodegradation is a dominant
      control on above-ground litter decomposition in this semi-arid ecosystem. Losses
      through photochemical mineralization may represent a short-circuit in the carbon
      cycle, with a substantial fraction of carbon fixed in plant biomass being lost
      directly to the atmosphere without cycling through soil organic matter pools.
      Furthermore, future changes in radiation interception due to decreased
      cloudiness, increased stratospheric ozone depletion, or reduced vegetative cover
      may have a more significant effect on the carbon balance in these water-limited
      ecosystems than changes in temperature or precipitation.

PMID- 16885983
TI  - Record of mid-Archaean subduction from metamorphism in the Barberton terrain,
      South Africa.
AB  - Although plate tectonics is the central geological process of the modern Earth,
      its form and existence during the Archaean era (4.0-2.5 Gyr ago) are disputed.
      The existence of subduction during this time is particularly controversial
      because characteristic subduction-related mineral assemblages, typically
      documenting apparent geothermal gradients of 15 degrees C km(-1) or less, have
      not yet been recorded from in situ Archaean rocks (the lowest recorded apparent
      geothermal gradients are greater than 25 degrees C km(-1)). Despite this absence
      from the rock record, low Archaean geothermal gradients are suggested by
      eclogitic nodules in kimberlites and circumstantial evidence for subduction
      processes, including possible accretion-related structures, has been reported in
      Archaean terrains. The lack of spatially and temporally well-constrained high
      pressure, low-temperature metamorphism continues, however, to cast doubt on the
      relevance of subduction-driven tectonics during the first 1.5 Gyr of the Earth's
      history. Here we report garnet-albite-bearing mineral assemblages that record
      pressures of 1.2-1.5 GPa at temperatures of 600-650 degrees C from supracrustal
      amphibolites from the mid-Archaean Barberton granitoid-greenstone terrain. These
      conditions point to apparent geothermal gradients of 12-15 degrees C-similar to
      those found in recent subduction zones-that coincided with the main phase of
      terrane accretion in the structurally overlying Barberton greenstone belt. These
      high-pressure, low-temperature conditions represent metamorphic evidence for cold
      and strong lithosphere, as well as subduction-driven tectonic processes, during
      the evolution of the early Earth.

PMID- 16885984
TI  - The calmodulin pathway and evolution of elongated beak morphology in Darwin's
      finches.
AB  - A classic textbook example of adaptive radiation under natural selection is the
      evolution of 14 closely related species of Darwin's finches (Fringillidae,
      Passeriformes), whose primary diversity lies in the size and shape of their
      beaks. Thus, ground finches have deep and wide beaks, cactus finches have long
      and pointed beaks (low depth and narrower width), and warbler finches have
      slender and pointed beaks, reflecting differences in their respective diets.
      Previous work has shown that even small differences in any of the three major
      dimensions (depth, width and length) of the beak have major consequences for the
      overall fitness of the birds. Recently we used a candidate gene approach to
      explain one pathway involved in Darwin's finch beak morphogenesis. However, this
      type of analysis is limited to molecules with a known association with
      craniofacial and/or skeletogenic development. Here we use a less constrained,
      complementary DNA microarray analysis of the transcripts expressed in the beak
      primordia to find previously unknown genes and pathways whose expression
      correlates with specific beak morphologies. We show that calmodulin (CaM), a
      molecule involved in mediating Ca2+ signalling, is expressed at higher levels in
      the long and pointed beaks of cactus finches than in more robust beak types of
      other species. We validated this observation with in situ hybridizations. When
      this upregulation of the CaM-dependent pathway is artificially replicated in the
      chick frontonasal prominence, it causes an elongation of the upper beak,
      recapitulating the beak morphology of the cactus finches. Our results indicate
      that local upregulation of the CaM-dependent pathway is likely to have been a
      component of the evolution of Darwin's finch species with elongated beak
      morphology and provide a mechanistic explanation for the independence of beak
      evolution along different axes. More generally, our results implicate the CaM
      dependent pathway in the developmental regulation of craniofacial skeletal
      structures.

PMID- 16885985
TI  - Tumorigenic transformation by CPI-17 through inhibition of a merlin phosphatase.
AB  - The tumour suppressor protein merlin (encoded by the neurofibromatosis type 2
      gene NF2) is an important regulator of proliferation in many cell and tissue
      types. Merlin is activated by dephosphorylation at serine 518 (S518), which
      occurs on serum withdrawal or on cell-cell or cell-matrix contact. However, the
      relevant phosphatase that activates merlin's tumour suppressor function is
      unknown. Here we identify this enzyme as the myosin phosphatase (MYPT-1
      PP1delta). The cellular MYPT-1-PP1delta-specific inhibitor CPI-17 causes a loss
      of merlin function characterized by merlin phosphorylation, Ras activation and
      transformation. Constitutively active merlin (S518A) reverses CPI-17-induced
      transformation, showing that merlin is the decisive substrate of MYPT-1-PP1delta
      in tumour suppression. In addition we show that CPI-17 levels are raised in
      several human tumour cell lines and that the downregulation of CPI-17 induces
      merlin dephosphorylation, inhibits Ras activation and abolishes the transformed
      phenotype. MYPT-1-PP1delta and its substrate merlin are part of a previously
      undescribed tumour suppressor cascade that can be hindered in two ways, by
      mutation of the NF2 gene and by upregulation of the oncoprotein CPI-17.

PMID- 16885987
TI  - Choroid plexus cysts do not affect fetal neurodevelopment.
AB  - OBJECTIVE: To determine whether an isolated finding of a choroid plexus cyst
      (CPC) during routine ultrasound is associated with altered fetal growth or
      development. STUDY DESIGN: Prospective, case-control study comparing 35 CPC cases
      to 67 controls. Neurobehavioral development assessment included 50 min long
      serial recordings of heart rate, motor activity and their interrelation at 24,
      28, 32 and 36 weeks gestation. Growth measurement was based on three ultrasound
      evaluations of femur length, biparietal diameter, head circumference and
      abdominal circumference at initial exam, 28 and 36 weeks. RESULTS: Longitudinal
      analyses revealed no differences in fetal heart rate, variability or
      accelerations; the number or duration of fetal movements or total motor activity;
      nor fetal movement-fetal heart rate coupling. CPC cases had slightly smaller head
      and abdominal circumferences at 28 weeks, but these differences had disappeared
      by 36 weeks. CPC detection was more common when routine exams were conducted
      earlier (18.8 versus 19.5 weeks; P<0.01). CONCLUSION: Despite the presumption
      that CPCs with normal karyotypes are benign variants, little empirical support
      exists. These results indicate that CPCs detected by prenatal ultrasound do not
      pose or reveal a threat to fetal development.

PMID- 16885988
TI  - Equations describing percentiles for birth weight, head circumference, and length
      of preterm infants.
AB  - OBJECTIVE: To describe growth of prematurely born infants and create a growth
      chart adequate to assess growth of infants with less than 29 completed weeks of
      gestation. STUDY DESIGN: Birth weight, head circumference and length measurements
      of 7,425 liveborn preterm infants from 1985 to 1997 were retrieved from a
      longitudinal database maintained by the neonatology division. The 3rd, 5th, 10th,
      15th, 25th, 50th, 75th, 85th, 90th, 95th and 97th percentiles of each measurement
      were determined and used for mathematical modeling. RESULTS: Birth weight was
      described with an exponential function while head circumference and length were
      described with linear functions. A preterm growth chart for the 10th, 50th and
      90th percentiles for birth weight, weight growth, head circumference and length
      was generated. CONCLUSION: The mathematical models of growth provide smooth
      representations of the percentiles across gestational ages.

PMID- 16885989
TI  - Adjustable fortification of human milk fed to preterm infants: does it make a
      difference?
AB  - BACKGROUND: Inadequate nutrition leading to growth failure is common among
      premature infants. Although fortified breast milk (breast milk plus commercially
      prepared fortifier) is the preferred feeding, nutrient intakes achieved with
      fortified breast milk fall short of meeting nutrient needs. This is mainly due to
      inadequate protein content of fortifiers and variability in composition of
      expressed breast milk. OBJECTIVE: A new adjustable fortification regimen has been
      designed to ensure that protein needs of premature infants are met at all times.
      The new regimen encompasses increasing the amount of fortifier and adding extra
      protein to breast milk guided by periodic determinations of blood urea nitrogen
      (BUN). The study tested the hypothesis that infants fed according to the new
      regimen have higher protein intakes and improved weight gain compared to infants
      fed according to standard fortification regimen. METHODS: In a prospective,
      controlled trial, preterm infants with birth weights of 600-1750 g and
      gestational ages between 26 and 34 weeks were fed their own mother's milk or
      banked donor milk or both. Infants were randomly assigned before 21 days of age
      to either the new adjustable fortification regimen or the standard regimen. The
      study period began when feeding volume reached 150 ml/kg/day and ended when
      infants reached a weight of 2000 g. Standard fortification (STD) consisted in the
      use of the recommended amount of fortifier. Adjustable fortification (ADJ)
      consisted in the use, in addition to standard fortification, of extra fortifier
      and supplemental protein guided by twice-weekly BUN determinations. The primary
      outcome was weight gain, with serum biochemical indicators and nutrient intakes
      as secondary outcomes. RESULTS: Thirty-two infants completed the study as planned
      (16 ADJ, 16 STD). Infants receiving the ADJ regimen had mean protein intakes of
      2.9, 3.2 and 3.4 g/kg/day, respectively, in weeks 1, 2 and 3, whereas infants
      receiving the STD regimen had intakes of 2.9, 2.9, 2.8 g/kg/day, respectively.
      Infants on the ADJ regimen showed significantly greater gain in weight (17.5+/
      3.0 vs 14.4+/-3.0 g/kg/day, P<0.01) and greater gain in head circumference (1.4+/
      0.3 vs 1.0+/-0.3; P<0.05) than infants on the STD regimen. Weight and head
      circumference gain were significantly (P<0.05) correlated with protein intake. No
      significant correlations were found between growth parameters and intake of fat
      and energy. There were no significant differences between groups in BUN and other
      serum chemical values. In the ADJ group, BUN concentrations increased
      significantly (P<0.001) over time but were not significantly higher than in the
      STD group. CONCLUSION: Premature infants managed with the new adjustable
      fortification regimen had significantly higher weight and head circumference
      gains than infants managed with standard fortification. Higher protein intake
      appears to have been primarily responsible for the improved growth with the
      adjustable regimen. The new fortification method could be a solution to the
      problem of protein undernutrition among premature infants fed human milk.

PMID- 16885990
TI  - Surfactant era (1990-2002) 2-year outcomes of infants less than 1500 g from a
      Community Level 3 Neonatal Intensive Care Unit.
AB  - OBJECTIVE: To report Bayley scores of 572 twenty-four-month corrected age infants
      whose birth weights (BWs) were less than 1500 g cared for in a Community Level 3
      Neonatal Intensive Care Unit (NICU) between 1990 and 2002 when surfactant was
      routinely used. STUDY DESIGN: Survival, "normal" defined as both Mental
      Developmental Index (MDI) and Psychomotor Developmental Index (PDI)>84, MDI>69
      and MDI>84 were analyzed by gestational age (GA) and BW. Comparisons were made
      between infants born pre- and post-1996 when high-frequency oscillatory
      ventilation came into frequent use, Medicaid and non-Medicaid infants, multiples
      and singletons, outborn and inborn infants, boys and girls and infants with
      intrauterine growth retardation (IUGR) and those appropriate for gestational age
      (AGA). RESULTS: There was a correlation between GA and BW and improving outcomes.
      Scores do not approach those of normal standardization sample populations (60%
      for "normal", 68% for MDI>84 and 95% for MDI>69) until 1400 g and 30 weeks.
      Medicaid, outborn and IUGR infants, and boys did worse in some aspects.
      CONCLUSION: There was a correlation between both GA and BW and improving
      outcomes. Availability of these developmental data on a laminated pocket card can
      facilitate presentation of outcome experience to families by pediatric and
      obstetric caregivers.

PMID- 16885991
TI  - Are consecutive nightly recordings required for valid evaluation of sleep
      associated erections?
AB  - We questioned the need for more than one RigiScan recording for accurate
      assessment of sleep-associated penile erections and determine the necessity of
      consecutive nightly recordings for valid evaluation of sleep-associated
      erections. Men complaining of erectile dysfunction (ED) and referred to RigiScan
      evaluation for the first time participated. Recordings were performed at the
      patient's home during two consecutive nights, and data on test time, number of
      erections, erection duration, minimal and maximal base and tip tumescence and
      rigidity were retrieved for both nights. Normal erectile function was defined
      with the recording of at least one erection (70 out of 100% tip rigidity lasting
      for at least 10 min during either night). The main outcome measures were RigiScan
      recordings. Group 1 consisted of 29 men (mean age 42.4+/-13.8 years, range 22-71)
      who had normal erections, all during the first night. Group 2 consisted of 26 men
      (mean age 48.6+/-13.5 years, range 25-70) who failed to fulfill both criteria for
      normal erection. In Group 2, only the values for penile base rigidity and
      erection duration were normal during the first night: the parameters of maximal
      base tumescence, tip rigidity, number of effective erections and duration of
      effective erections that were impaired during the first night were significantly
      worse (P<0.01) during the second night. The required information for the
      diagnosis of psychogenic ED was obtained during the first night in >50% of the
      participants. Men with normal erections during the first night can be spared the
      inconvenience and cost of re-testing. Consecutive night recording should be
      reserved for patients whose recorded data during the first night did not fulfill
      the criteria for normal erection.

PMID- 16885992
TI  - Prevalence of erectile dysfunction among middle-aged men in a metropolitan area
      in Germany.
AB  - The comparison of results of previous studies on the prevalence of erectile
      dysfunction is hampered due to differences in study design and research
      instruments including definitions used. The aim of the study was to determine the
      prevalence of erectile dysfunction/erectile disorder (ED) using different
      definitions. An epidemiological cross-sectional study was conducted between May
      and November 2002 in Berlin, Germany. A total of 6000 men between 40 and 79 years
      of age were randomly selected by the Berlin Office of Vital Statistics and were
      sent a questionnaire by mail. The prevalence of ED was determined using five
      different methods. A total of 1915 questionnaires were eligible for analysis. The
      five different definitions yielded age-adjusted ED prevalence rates between 18
      and 48%. Age was strongly correlated with all five definitions (P<0.001). These
      results indicate the need for standardized criteria when conducting future
      studies on ED and may aid in designing public health and clinical management
      strategies.

PMID- 16885993
TI  - Expression of myosin isoforms in the smooth muscle of human corpus cavernosum.
AB  - The molecular interaction between smooth muscle (SM) myosin and actin in the
      corpus cavernosum (CC) determines the erectile state of the penis. A key
      mechanism regulating this interaction and subsequent development and maintenance
      of force is alternative splicing of SM myosin heavy chain (MHC) and 17 kDa
      essential SM myosin light chain (MLC) pre-mRNAs. Our aim was to examine the
      relative SM myosin isoform composition in human CC. Tissue samples were obtained
      from 18 patients with erectile dysfunction (ED), Peyronie's disease, or both. One
      specimen was obtained during a transgender operation. Patients then were
      stratified according to presence of diabetes mellitus, hypertension, ED, or
      Peyronie's disease, as well as failure of phosphodiesterase-5 (PDE5) inhibitors
      and history of previous pelvic or penile surgeries, radiation, or both. Our
      results revealed that all human CC samples expressed only the SM-A isoform. There
      was a predominance of SM2 isoform mRNA relative to SM1 across all samples, with a
      mean of 63.8%, which correlated with protein analysis by gel electrophoresis. A
      statistically significant difference was found between patients who had undergone
      previous pelvic surgery, radiation, or both and those who did not. The ratio of
      LC(17b) to LC(17a) was approximately 1:1 for all patients, with a mean of 48.9%
      LC(17b). Statistical difference was seen in the relative ratio of LC(17b) to
      LC(17a) among the group who failed conservative therapy with PDE5 inhibitors
      compared with all others. In conclusion, we determined the SM myosin isoform
      composition of human CC and present for the first time differences in relative
      myosin isoform expression among patients with several risk factors contributing
      to their cause of ED. Our data reflect the fact that alternative splicing events
      in the MHC and 17 kDa MLC pre-mRNA may be a possible molecular mechanism involved
      in the altered contractility of the CCSM in patients with ED.

PMID- 16885996
TI  - Hypertension, diuretics and breast cancer risk.
AB  - It is unclear whether hypertension and antihypertensive medication use are
      associated with breast cancer. In order to examine these associations, we
      conducted a case-control study among women aged 50-75 years. Breast cancer cases
      were ascertained via a population-based cancer registry (n=523) and controls were
      ascertained via random-digit-dialing (n=131). Participants completed a self
      administered questionnaire which queried history of hypertension,
      antihypertensive medication use and risk factors. Unconditional logistic
      regression was used to estimate the odds ratio (OR) and 95% confidence intervals
      (CI), adjusted for age, body mass index (BMI), diabetes, smoking, alcohol use,
      menopausal status, family history of breast or ovarian cancer, age at first full
      term pregnancy and education. History of treated hypertension was associated with
      significant increased risk of breast cancer (OR, 1.77; 95% CI, 1.04-3.03) and
      this association appeared only in women with BMI > or =25 kg/m(2) (OR, 2.30; 95%
      CI, 1.12-4.71). Diuretic use was also associated with elevated breast cancer risk
      (OR, 1.79; 95% CI, 1.07-3.01). The risk associated with diuretic use increased
      with duration of use (P for trend, <0.01). Use of other blood pressure
      medications was not found to be associated with breast cancer risk. These results
      support a positive association between treated hypertension, diuretic use and
      breast cancer risk among women aged 50-75 years.

PMID- 16885997
TI  - Hypertension and breast cancer: an association revisited?

PMID- 16885998
TI  - Gene silencing by the tRNA maturase tRNase ZL under the direction of small-guide
      RNA.
AB  - We have been developing a unique system for the downregulation of a gene
      expression through cutting a specific mRNA by the long form of tRNA 3'-processing
      endoribonuclease (tRNase Z(L)) under the direction of small-guide RNA (sgRNA).
      However, the efficacy of this system and the involvement of tRNase Z(L) in the
      living cells were not clear. Here we show, by targeting the exogenous luciferase
      gene, that the efficacy of the sgRNA/tRNase Z(L) method can become comparable to
      that of the RNA interference technology and that the gene silencing is owing to
      tRNase Z(L) directed by sgRNA not owing to a simple antisense effect. We also
      show that tRNase Z(L) together with sgRNA can downregulate expression of the
      endogenous human genes Bcl-2 and glycogen synthase kinase-3beta by degrading
      their mRNAs in cell culture. Furthermore, we demonstrate that a gene expression
      in the livers of postnatal mice can be inhibited by an only seven-nucleotide
      sgRNA. These data suggest that sgRNA might be utilized as therapeutic agents to
      treat diseases such as cancers and AIDS.

PMID- 16885999
TI  - Enhanced toxicity of purine nucleoside analogs in cells expressing Drosophila
      melanogaster nucleoside kinase mutants.
AB  - The multisubstrate deoxyribonucleoside kinase of Drosophila melanogaster (Dm-dNK)
      is investigated for possible use as a suicide gene in combined gene/chemotherapy
      of cancer. The enzyme has broader substrate specificity and higher catalytic rate
      compared to herpes simplex type 1 thymidine kinase and other known dNKs. Although
      the enzyme has broad substrate specificity, it has a preference for pyrimidine
      nucleosides and nucleoside analogs. We have evaluated the substrate specificity
      and kinetic properties of Dm-dNK proteins containing M88R, V84A+M88R or
      V84A+M88R+A110D mutations in the amino-acid sequence. These engineered enzymes
      showed a relative increase in phosphorylation of purine nucleoside analogs such
      as ganciclovir, 9-beta-D-arabinofuranosylguanine and 2',2'-difluorodeoxyguanosine
      compared to the wild-type enzyme. The mutant enzymes were expressed in an
      osteosarcoma thymidine kinase-deficient cell line and the sensitivity of the cell
      line to nucleoside analogs was determined. The cells expressing the M88R mutant
      enzyme showed the highest increased sensitivity to purine nucleoside analogs with
      8- to 80-fold decreased inhibition constant IC(50) compared to untransduced
      control cells or cells expressing the wild-type nucleoside kinase. In summary,
      our data show that enzyme engineering can be used to shift the substrate
      specificity of the Dm-dNK to selectively increase the sensitivity of cells
      expressing the enzyme to purine nucleoside analogs.

PMID- 16886000
TI  - Coxsackie adenovirus receptor and alpha nu beta3/alpha nu beta5 integrins in
      adenovirus gene transfer of rat cochlea.
AB  - This study was designed to determine whether Coxsackie adenovirus receptor (CAR)
      and alpha nu beta3/alpha nu beta5 integrin co-receptors are involved in
      adenovirus gene transfer in the rat cochlea. We find that CAR and integrin co
      receptors are expressed in every cell subtype transduced by the adenoviral vector
      Ad5 DeltaE1-E3/cytomegalovirus/green fluorescent protein (GFP) on cochlear slices
      in vitro. The spiral ganglion neurons, which do not express CAR, were not
      transduced by the virus. Blocking these receptors by monoclonal antibodies
      decreased transgene expression, whereas disrupting tight junctions with
      ethylenediaminetetraacetic acid led to an increased transgene expression.
      However, sensory hair cells and strial cells also expressing CAR and alpha nu
      integrins were not transduced by the vector. GFP expression was also studied in
      vivo. Perilymphatic perfusion of adenovirus in vivo did not affect hearing and
      only cells lining the perilymphatic spaces were transduced. Endolymphatic
      perfusion resulted in low-frequency hearing loss and although some cells of the
      organ of Corti were efficiently transduced, the sensory and the strial cells were
      not. Transduced sensory and strial cells were occasionally observed in cochleas
      after single shot of adenovirus. Pretreatment with anti-CAR and anti-alpha nu
      antibodies decreases GFP expression in vivo, suggesting that the CAR/alpha nu
      integrin pathway is involved in adenovirus transduction in the cochlea.

PMID- 16886001
TI  - Systemic co-administration of depsipeptide selectively targets transfection
      enhancement to specific tissues and cell types.
AB  - Depsipeptide, a histone deacetylase (HDAC) inhibitor, kills tumor cells much more
      effectively than normal cells, and can produce significant antitumor activity in
      human cancer patients. Depsipeptide also increases the expression of lipoplex
      delivered genes in cultured tumor cells, as well as following direct intra
      tumoral injection. We now show that co-intravenous (i.v.) injection of
      depsipeptide with polyethylenimine (PEI):DNA complexes significantly increases
      the expression of PEI-delivered genes in normal, as well as in tumor-bearing
      mice. At the tissue level, depsipeptide-mediated enhancement of gene expression
      was selectively targeted to the lung, liver and spleen. At the cellular level,
      depsipeptide significantly increased the expression of the i.v., PEI co-delivered
      wild-type human p53 gene in metastatic breast cancer cells, but not in adjacent
      normal cells. Thus, the ability of depsipeptide to enhance the expression of
      systemically delivered genes is selectively targeted at both the tissue and
      cellular levels, without requiring the use of ligand- or promoter-based
      approaches. Analyzing HDAC-based targeting of gene expression may identify host
      genes that control the expression of systemically delivered genes.

PMID- 16886002
TI  - Gene therapy to inhibit xenoantibody production using lentiviral vectors in non
      human primates.
AB  - Xenoantibodies to the gal alpha1,3 gal (gal) epitope impede the use of pig
      tissues for xenotransplantation, a procedure that may help overcome the shortage
      of human organ donors. Stable gal chimerism and tolerance to gal(+) hearts could
      be achieved in alpha1,3-galactosyltransferase (alpha1,3GT)(-/-) mice using
      lentiviral vectors expressing porcine alpha1,3GT, the enzyme that synthesizes the
      gal carbohydrate. In this study, we evaluated whether chimerism sufficient to
      inhibit anti-gal xenoantibody responses can be achieved using lentivectors in non
      human primates. Rhesus macaques were transplanted with autologous, alpha1,3GT
      transduced bone marrow (BM) following sublethal irradation. Simian
      immunodeficiency virus (SIV)- and human immunodeficiency virus (HIV)-1-derived
      lentiviral constructs were compared. Chimerism was observed in several
      hematopoietic lineages in all monkeys. Engraftment in animals receiving SIV-based
      alpha1,3GT constructs was similar to that achieved using the HIV-1-derived
      lentivector for the first 2 months post-transplantation, but increased thereafter
      to reach higher levels by 5 months. Upon immunization with porcine hepatocytes,
      the production of anti-gal immunoglobulin M xenoantibody was substantially
      reduced in the gal(+) BM recipients compared to controls. This study is the first
      to report the application of gene therapy to achieve low-level, long-term gal
      chimerism sufficient to inhibit production of anti-gal antibodies after
      immunization with porcine cells in rhesus macaques.

PMID- 16886003
TI  - Telling it like it was.

PMID- 16886004
TI  - Helical proteins initiate replication of DNA helices.

PMID- 16886005
TI  - Where to start and when to stop.

PMID- 16886007
TI  - A helicase staircase.

PMID- 16886008
TI  - Stirring the POT1: surprises in telomere protection.

PMID- 16886011
TI  - Electrical stimulation induced lumbar medial branch referral patterns.
AB  - STUDY DESIGN: Fluoroscopically guided, minimum threshold electrical stimulation
      of the right first, second, third, and fourth lumbar medial branches and the
      fifth lumbar dorsal ramus in each of eight healthy test subjects was performed.
      The stimulation thresholds and referral patterns were recorded. A composite
      drawing of the referral patterns was created. The composite drawings were
      compared to documented referral patterns already published by other authors.
      OBJECTIVE: To determine the referral patterns of the lumbar medial branches and
      the fifth lumbar dorsal ramus. HYPOTHESIS: The lumbar medial branch referral
      patterns created by minimum threshold electrical stimulation may differ from
      those obtained after zygapophysial joint (Z-joint) injections. SUMMARY OF
      BACKGROUND DATA: Lumbar Z-joint referral patterns have been identified following
      provocative Z-joint injections. There are no reports of lumbar medial branch
      referral patterns. METHODS: The right L1 through L4 medial branch of the
      posterior primary ramus and the right L5 dorsal ramus in each of eight healthy
      volunteer males (n=40), without a history of back pain, were electrically
      stimulated under fluoroscopic imaging. All subjects were blinded to the level of
      stimulation, and each individual mapped out the referral area on a human line
      drawing at the time of each stimulus. The referral patterns after electrical
      stimulation and the stimulation thresholds were recorded. These referral patterns
      were compared to referral patterns recorded during provocative Z-joint injections
      by other authors. CONCLUSION: All of the subjects' mapped referral sites
      coincided with each other, creating a well defined composite drawing. These
      referral zones are different than those reported after injection of the lumbar Z
      joint, which may have clinical and therapeutic implications. These referral maps
      may provide the clinician with additional insight when evaluating a patient with
      lumbar, flank, or gluteal pain of undetermined etiology.

PMID- 16886010
TI  - Leading the way in interventional pain management.

PMID- 16886012
TI  - Evaluation of the prevalence of facet joint pain in chronic thoracic pain.
AB  - The role of zygapophysial (facet) joints in chronic thoracic pain has received
      very little attention with only a few publications discussing these joints as
      sources of pain. In contrast, facet joints have been implicated as responsible
      for chronic pain in a significant proportion of patients with chronic neck and
      low back pain. However, thoracic spinal pain, though less common, has been
      reported to be as disabling as neck and low back pain. This study was designed to
      evaluate all the consecutive patients presenting with thoracic pain and
      undergoing diagnostic medial branch blocks during 2001. All the patients failed
      conservative management with physical therapy, chiropractic therapy and drug
      therapy. All patients underwent diagnostic facet joint nerve blocks using
      lidocaine 1%, initially followed by bupivacaine 0.5% on separate occasions.
      Results showed that 46 patients underwent single blocks with lidocaine and 36 of
      these patients, or 78%, were positive for facet joint pain, reporting a definite
      response. Confirmatory blocks with bupivacaine were performed in all patients who
      were lidocaine-positive, with 61%, or 48% of the total sample of the lidocaine
      positive group, reporting a definite response with improvement in their pain.
      Thus, comparative local anesthetic blocks showed the prevalence of facet joint
      pain to be 48%, with single blocks carrying a false-positive rate of 58%.

PMID- 16886013
TI  - A prospective outcomes study of patients undergoing intradiscal electrothermy
      (IDET) for chronic low back pain.
AB  - This prospective, non-randomized clinical trial was designed to determine the
      clinical outcome of patients who underwent Intradiscal Electrotherapy (IDET) for
      the treatment of chronic discogenic low back pain. Twenty-seven consecutive
      patients undergoing IDET were prospectively evaluated. All patients, as
      determined by provocative discography and/or MRI, had discogenic disease with
      chronic low back pain and were non-responsive to conservative treatment for at
      least 6 months. The mean pre-operative duration of symptoms was 38 months. The
      American Association of Neurological Surgeons/Congress of Neurological Surgeons
      Joint Section Lumbar Disc Herniation Study Questionnaire, which includes the
      Oswestry Low Back Pain Disability Questionnaire and the Short Form (SF) -36
      Health Status Questionnaire, was used. The follow-up endpoint for all patients
      was one year. Seventy-five percent of patients improved based upon the Oswestry
      Low Back Pain Disability Questionnaire while only 48% of patients were found to
      improve on the SF-36 Survey. The SF-36 Bodily Pain Subscale did improve relative
      to other subscales in 52% of patients. There was no relationship found between
      outcome and duration of symptoms (p= .32), number of levels treated (p= .20), or
      worker's compensation (p= .38). There were no complications that resulted from
      the IDET treatment. IDET was found to be effective in 75% of patients in
      improving their chronic low back pain. This did not translate into a significant
      improvement in the SF-36 survey scores. The risks are negligible, and recovery
      time is minimal. The procedure may be useful in selected patients who would
      otherwise undergo an interbody fusion procedure.

PMID- 16886014
TI  - Is there correlation of facet joint pain in lumbar and cervical spine? An
      evaluation of prevalence in combined chronic low back and neck pain.
AB  - Among the chronic pain problems, pain emanating from cervical and lumbar regions,
      independently or in combination, constitutes a significant and frequently
      encountered problem in interventional pain management practices. This study was
      designed to test the assumption that patients presenting with chronic low back
      pain of lumbar facet joint origin may also present with chronic neck pain of
      facet joint origin. Considering that many studies show the prevalence of facet
      joint involvement in chronic low back pain as ranging from 15% to 45% compared to
      prevalence of involvement of cervical facets in chronic neck pain, ranging from
      54% to 60%, we sought to evaluate the correlation between lumbar facet joint to
      cervical facet joint pain. One hundred twenty consecutive patients with chronic
      neck and low back pain were evaluated utilizing controlled diagnostic blocks with
      lidocaine and bupivacaine. The results showed prevalence of cervical facet joint
      pain in 67% of the patients with a false-positive rate of 63% with a single
      block, whereas the prevalence of lumbar facet joint pain was seen in 40% of the
      patients with a 30% false-positive rate with a single block in patients
      presenting with chronic low back and neck pain. There was also significant
      correlation noted with 94% of the patients with confirmed lumbar facet joint pain
      also presenting with cervical facet joint pain.

PMID- 16886015
TI  - Anatomy of the intervertebral foramen.
AB  - The intervertebral foramen serves as the doorway between the spinal canal and
      periphery. It lies between the pedicles of neighboring vertebrae at all levels in
      the spine. A number of categorization schemes have been attempted to describe the
      boundaries of the intervertebral foramen. No uniform agreement has been made on
      which classification best describes this area. Studies of the nerve root canals
      have clearly noted variations in the angle of take-off from the thecal sac,
      length of the nerve root, and placement of the dorsal root ganglion from
      different lumbar levels. The nerve root canal receives a dual blood supply from
      central and peripheral sources. The dorsal root ganglion also has a dual vascular
      supply that aids in preventing damage to this vital foraminal structure. The
      presence of ligamentous structures within the foramen has been demonstrated by a
      number of recent studies. These ligaments serve a protective and organizational
      role for the neurovascular structures of the foramen. A thorough knowledge of the
      intervertebral foramen will allow the understanding of the pathological and
      degenerative changes that cause compression or injury to these foraminal
      structures.

PMID- 16886016
TI  - Endplate fracture associated with intradiscal dextrose injection.
AB  - Intradiscal injections have been used for many years in the treatment of chronic
      pain. These injections consisted of many substances providing variable pain
      relief from discogenic pain. Following an intradiscal dextrose injection series,
      a physically active patient developed superior and inferior lumbar endplate
      fractures, producing a drastic increase in pain. The pathology of endplate
      fractures and their contribution to chronic low back pain is subsequently
      reviewed. A discussion of various intradiscal agent injections is included. Also,
      the pathophysiology of the production of endplate fractures as related to
      intradiscal injections is discussed.

PMID- 16886018
TI  - Spinal cord mechanics during flexion and extension of the cervical spine: a
      finite element study.
AB  - The cervical spinal cord is at a great risk for injury during traumatic accidents
      occurring within people of relatively young age. Spinal cord injury can not be
      easily characterized clinically nor through in vitro testing. An understanding of
      cervical spinal cord deformation is important for defining an injury threshold of
      the spinal cord. Therefore, an analytical method may be beneficial for
      determining the response of the spinal cord response to external loads on the
      spine. We have developed a three-dimensional, non-linear finite element model to
      quantify physiologic strains and stresses in the cervical spinal cord placed in
      the ligamentous C5-C6 motion segment. Compressive loads along with flexion and
      extension moments were applied to the bony segment and not the cord itself.
      Motion data, shown in degrees of movement in flexion and extension calculated for
      the model showed a close representation to in vivo data. Von Mises stress plots
      and strains on the cervical spinal cord were computed. This model represents a
      first attempt by the authors to analytically quantify the mechanical response of
      the spinal cord to cervical spine injury.

PMID- 16886017
TI  - Radiation exposure to the physician in interventional pain management.
AB  - Fluoroscopy is an integral part of the practice of interventional pain management
      in present day modern medical practices. The major purpose of fluoroscopy in
      interventional pain management is correct needle placement to ensure target
      specificity and accurate delivery of the injectate. Fluoroscopy has become
      mandatory for multiple procedures based either on the definition of the procedure
      or the requirement of third parties. The most commonly used fluoroscopy in
      interventional pain management is with C-arm fluoroscopes with image
      intensification. Fluoroscopy is associated with risk for patients, clinicians,
      and the personnel in the operating room unless it is managed with appropriate
      understanding, skill, and vigilance. A total of 1,000 consecutive patients
      undergoing interventional procedures with chronic pain performed by one physician
      were studied. Two fluoroscopy units were utilized and operated by two certified
      radiological technologists. The procedures performed included caudal and
      interlaminar epidural injections, facet joint nerve blocks, percutaneous
      adhesiolysis, intercostal nerve blocks, sympathetic blocks, transforaminal
      epidural injections, along with other procedures. Results showed that a total of
      1,000 patients underwent 1,729 procedures with average radiation exposure of 13.2
      +/- 0.33 seconds per patient and 7.7 +/- 0.21 seconds per procedure. Dosimetry
      measurements showed total exposure of 1,345 mREM outside the apron and 0 mREM
      inside the apron during this period. The average exposure outside the apron was
      1.345 mREM per patient and 0.778 mREM per procedure outside the apron and 0 mREM
      inside the apron. The levels of exposure are significantly below the annual
      limits recommended. It is concluded that it is feasible to perform all procedures
      under fluoroscopy in the described setting safely and effectively in
      interventional pain management.

PMID- 16886019
TI  - Compression fracture: identify the diagnosis.

PMID- 16886020
TI  - Medial branch neurotomy in management of chronic spinal pain: systematic review
      of the evidence.
AB  - Zygapophysial or facet joints have been implicated as cause of low back, mid
      back, upper back and neck pain with referred pain. Cervical, thoracic and lumbar
      facet joints are innervated by the medial branches of the dorsal rami.
      Zygapophysial (facet) joints have been implicated as the source of chronic pain
      in 15% to 45% of the patients with chronic low back pain, 54% to 60% of the
      patients with chronic neck pain and 48% of the patients with thoracic pain. A
      systematic review of the evidence of effectiveness of radiofrequency denervation
      in the management of chronic spinal pain was undertaken. This review included
      randomized clinical trials, as well as non-randomized or observational studies in
      the analysis. Literature search included MEDLINE, EMBASE, systematic reviews,
      narrative reviews, cross-references to the reviews and various published trials;
      and peer reviewed abstracts from scientific meetings during the past two years.
      An algorithmic approach was followed in study evaluation with a description of
      inclusion and exclusion criteria. A set of high-performing scales or checklists
      pertaining to randomized clinical trials and observational trials derived from
      the Agency for Healthcare Research and Quality (AHRQ) was utilized; Systems to
      Rate the Strength of Scientific Evidence. Qualitative analysis was conducted,
      using five levels of evidence for effectiveness of medial branch neurotomy. Our
      search strategy identified over 1,000 citations as the result of electronic and
      manual screening. A total of 7 randomized trials of radiofrequency neurotomy for
      spinal pain were identified. However, only 4 related to medial branch neurotomy.
      Two of the four met the inclusion criteria. Among the multiple observational
      studies considered for inclusion, 4 prospective evaluations were included in the
      systematic review. In addition, 3 retrospective evaluations were also included.
      Two randomized trials comprised of 27 patients receiving active treatment. The
      first study consisted of cervical facet joint pain and the second consisted of
      lumbar facet joint pain. Both studies showed positive results. Similar to
      randomized trials, prospective, as well as retrospective evaluations showed
      positive evidence, both in short-term and long-term. The results of this
      systematic review of 2 well-designed randomized trials, 4 prospective well
      designed trials without randomization and 3 retrospective evaluations provided
      strong evidence that radiofrequency denervation offers short-term relief and
      moderate evidence of long-term pain relief of facet joint origin.

PMID- 16886021
TI  - Painless foot drop: an atypical etiology of a common presentation.
AB  - Weakness of the dorsiflexor muscles of the foot is a relatively common
      presentation. In most cases, the etiology involves a peripheral injury to the
      common peroneal nerve. These patients usually present with lower motor neuron
      findings on evaluation. In contrast, if upper motor neuron findings were present
      a central lesion should be suspected and appropriate imaging studies are
      performed. We describe a patient with painless foot drop and lower motor findings
      on examination that was diagnosed with multiple sclerosis. This case demonstrates
      that multiple sclerosis can masquerade as a peripheral process in some patients.

PMID- 16886023
TI  - Keeping pace with HIPAA's changes: straight talk from the trenches.
AB  - Over the past several months, the Department of Health and Human Services (DHHS)
      has issued new final and proposed rules pursuant to the Health Insurance
      Portability and Accountability Act of 1996 (HIPAA). The privacy rule was
      finalized on August 14, 2002. Changes made to the original rule were in general
      beneficial to providers. Consent forms will no longer be required for treatment,
      although providers may choose to continue to use them. Physicians will still be
      required to use and disclose only the "minimum necessary" protected health
      information (PHI) to accomplish the purpose for which the information is being
      used or disclosed, but the new final rule excludes some situations in which the
      minimum necessary requirement will apply. A model business associates contract is
      provided in the final rule, making it easier for providers to comply with the
      rule's requirement that they have written business associate contracts with
      vendors who need access to the provider's PHI to perform tasks on behalf of
      providers. Researchers now only need to provide one form for consent and
      authorization, instead of two. There are also proposed changes in the transaction
      rule. Certain data elements that were required by the final rule are now
      situational in the proposed rule. Unnecessary data elements have been removed.
      Certain items, like special program indicator codes, will now be able to be
      reported via external code sets rather than as data elements in a transaction.
      The proposed rule also adopts requests from the industry by adding data elements,
      codes, or loops to enable covered entities to perform certain business functions
      in the standardized transactions, such as cross-referencing two subscriber IDs
      (e.g., surviving spouse and dependents). A final rule was published in May 2002
      that created a standard employer identifier. The Employer Identifier Number (EIN)
      that is already in use by the IRS will be the standardized unique employer
      identifier number. A proposed rule to cease using the National Drug Codes in
      transactions for nonretail pharmacy transactions was published in May 2002. DHHS
      developed the proposal in response to widespread industry concern over the
      tremendous cost of implementing the National Drug Codes (NDC). The NDC will
      either not be replaced at all, or will be replaced by the HCPCS. This article is
      not, and should not be construed as, legal advice or an opinion on specific
      situations.

PMID- 16886022
TI  - Tizanidine is effective in the treatment of myofascial pain syndrome.
AB  - Myofascial pain syndrome (MPS) is difficult to treat. The efficacy and safety of
      tizanidine, an alpha2-adrenergic agent with effects on spasticity and pain, in
      treating MPS was evaluated. Female subjects (n = 29) with MPS of 9 to > 52 weeks'
      duration and mean age 37.5 (range 20-51) years, who also had reduced pressure
      thresholds, were enrolled. Subjects were titrated up to 12 mg of tizanidine over
      3 weeks and maintained for 2 weeks. Sleep was assessed via visual analog scale
      (VAS), pain intensity via short form McGill questionnaire including VAS,
      disability/level of function, and pressure threshold (tested by algometry) at
      baseline, weeks 3 and 5, and 1 week after tizanidine was discontinued. Patient
      and physician global assessments of treatment were reported at week 5. Twenty
      four subjects completed the study. Pain intensity and disability decreased
      significantly from baseline at weeks 3 and 5 and after washout (P < .001).
      Pressure threshold and sleep improved for all study periods (P < .001).
      Tizanidine was rated as good to excellent in relieving pain by 89% of subjects
      and 79% of physicians. No serious adverse events occurred. Tizanidine was
      effective in the treatment of MPS.

PMID- 16886024
TI  - Role of psychology in interventional pain management.

PMID- 16886026
TI  - Cassandra 's curse: Interventional pain management, policy and preserving meaning
      against a market mentality.

PMID- 16886027
TI  - Medicare in interventional pain management: A critical analysis.
AB  - Recent years have been quite eventful for interventional pain physicians with
      numerous changes in the Medicare payment system with a view for the future and
      what it holds for interventional pain management for 2006 and beyond. On February
      8, 2006, President Bush signed the Deficit Reduction Act of 2005, which cuts the
      federal budget by 39 billion dollars and Medicare and Medicaid by almost 11
      billion dollars over five years. The Act contains a number of important
      provisions that effect physicians in general and interventional pain physicians
      in particular. This Act provides one year, 0% conversion factor update in
      payments for physicians services in 2006. Medicare has four programs or parts,
      namely Medicare Parts A, B, C, and D, and two funds to pay providers for serving
      beneficiaries in each of these program. Part B helps pay for physician,
      outpatient hospital, home health, and other services for the aged and disabled
      who have voluntarily enrolled. Before 1922, the fees that Medicare paid for those
      services were largely based on physician's historical charges. Despite Congress's
      actions of freezing or limiting the fee increases, spending continued to rise
      because of increases in the volume and intensity of physician services. Medicare
      spending per beneficiary for physician services grew at an average annual rate of
      11.6% from 1980 through 1991. Consequently Congress was forced to reform the way
      that Medicare sets physician fees, due to ineffectiveness of the fee controls and
      reductions. The sustained growth rate (SGR) system was established because of the
      concern that the fee schedule itself would not adequately constrain increases in
      spending for physicians' services. The law specifies a formula for calculating
      the SGR, based on changes in four factors: (1) estimated changes in fees; (2)
      estimated change in the average number of Part B enrollees (excluding Medicare
      Advantage beneficiaries); (3) estimated projected growth in real gross domestic
      product (GDP) growth per capita; and (4) estimated change in expenditures due to
      changes in law or regulation. Overall, the frequency of utilization of
      interventional procedures has increased substantially since 1998. In 2006 and
      beyond, interventionalists will face a number of evolving economic and policy
      related issues, including reimbursement discrepancies, issues related to CPT
      coding, issues related to utilization, fraud, and abuse.

PMID- 16886028
TI  - Fluoroscopic axial imaging in percutaneous lumbosacral procedures: An
      underutilized technique.
AB  - BACKGROUND: The L4-5 and L5-S1 intervertebral disc spaces are the most frequent
      sites of discal spinal pathology, hence, diagnostic and therapeutic interventions
      are commonly performed at these levels. While performing fluoroscopically guided
      spinal procedures such as discography or intradiscal electrothermal anuloplasty
      (IDEA), antero-posterior (AP), lateral, and oblique views are utilized. However
      axial projection is not typically possible without three-dimensional imaging such
      as computerized tomography (CT). Intraprocedural CT is not commonly available.
      Instead, post-discography CT axial views are used to grade the degree of
      disruption. However, post-procedural CT is not always immediately available, and
      it increases costs and may increase patient discomfort, inconvenience, and
      radiation exposure. Intra-procedure fluoroscopic axial (F-axial) views offer the
      benefit of dynamic information by helping confirm needle, introducer, or
      intradiscal catheter position. OBJECTIVE: To describe an alternative approach to
      axial imaging of the L5-S1 intradiscal space. SETTING: Spine Speciality Center.
      TECHNIQUE: We describe a simple technique for visualizing L5-S1 axial images
      intra-procedurally using F-axial views. Taking advantage of the patient's
      lordosis, the C-arm image intensifier is rotated cadally so F-axial images are
      obtained. We also demonstrate other uses of intra-procedural F-axials, including
      confirmation of discography needle placement and IDEA introducer and catheter
      positioning. CONCLUSION: The L4-5 and L5-S1 intervertebral disc spaces are
      frequent sites of discal spinal pathology. Multiple diagnostic and therapeutic
      procedures are performed at these levels. This report describes an adjunctive
      technique for visualizing the L5-S1 axial images intra-procedurally using a
      fluoroscopic axial (F-axial) view.

PMID- 16886029
TI  - The efficacy of a two needle electrode technique in percutaneous radiofrequency
      rhizotomy:An investigational laboratory study in an animal model.
AB  - BACKGROUND: Radiofrequency neurotomies are used to help reduce pain caused by
      structures innervated by the medial branch of the dorsal spinal nerve. The
      duration of effect may vary proportionally to the length of nerve coagulated.
      Techniques used to maximize the length of nerve within the radius of maximal heat
      include making multiple lesions, using larger needles, positioning the exposed
      needle parallel to the target nerve, and attempting more precise placement using
      50 hertz test stimulation. A variation of the technique uses two needles that are
      simultaneously placed to lie parallel to one another and parallel to the probable
      area the target nerve is known to traverse. Heating both needles at the same time
      would be a faster method that theoretically might also include more tissue within
      the heating radius of the needle lengths. OBJECTIVE: The purpose of this study
      was to confirm that two parallel radiofrequency lesions increased the volume of
      tissue included within the heating radius of the exposed needle tips, to
      determine optimal heating parameters, and to establish how far apart the needles
      can be placed and still achieve temperatures between the needles that will
      coagulate nerves. STUDY DESIGN: Investigational laboratory study in an animal
      model. METHODS: Ex-vivo porcine spinal tissue samples were prepared following a
      standardized protocol and two needle electrodes were connected to the Stryker
      rhizotomy device. A series of tissue samples were prepared with the needles
      placed 1, 1.5, 2, 3, 4, 5, 6, 7, 8, or 9 mm apart in respective samples. The
      needles were positioned parallel to the surface, and perpendicular to the tissue.
      In one series of samples, two needle electrodes were heated sequentially for each
      needle placement. Temperature parameters ranged from 60 to 100 degrees C and the
      time duration ranged from 60 to 90 seconds for each electrode. After each
      heating, all tissue was dissected and the size of the coagulated area measured.
      Temperatures at the midpoint between the two needle electrodes were monitored and
      measured with a Radionics needle sensor. Using the same study protocol and
      evaluation, a second set of samples was studied but both needle electrodes were
      heated simultaneously. RESULTS: Maximal lesion size was observed when the
      temperature of the electrode was higher than 70-80 degrees C and maintained for
      longer than 70 seconds. When the needles were heated sequentially, the needles
      could be placed no further than 1.5 to 2 mm apart before areas of incomplete
      coagulation were visualized at the midpoint between the needles. When both
      needles were simultaneously heated the needles could be placed 4 mm apart before
      incomplete coagulation was visualized. With simultaneous heating, the highest
      peak temperature of the midpoint between two needles (6 mm apart) exceeded 66
      degrees C, compared to a temperature of 40 degrees C achieved with sequential
      heating. CONCLUSIONS: This research confirms the efficacy of utilizing two needle
      electrodes during lumbar facet rhizotomy in an experimental model. Heating the
      two electrodes sequentially appears to coagulate a wider area and thus would be
      more likely to include a longer length of the target nerve and thus potentially
      could achieve better results in less time.

PMID- 16886030
TI  - Controlled substance abuse and illicit drug use in chronic pain patients: An
      evaluation of multiple variables.
AB  - BACKGROUND: Opioids are used extensively for chronic pain management in the
      United States. The frequency of opioid use prior to presenting to interventional
      pain management settings and in interventional pain management settings has been
      shown to be above 90%. Opioid abuse has been demonstrated in 9% to 41% of
      patients receiving chronic pain management. Illicit drug use has been reported in
      14% to 34% of patients in chronic pain management settings. OBJECTIVES: To
      evaluate and correlate multiple variables with opioid abuse and illicit drug use.
      DESIGN: A prospective, consecutive study. SETTING: Interventional pain management
      practice setting in the United States. METHODS: A total of 500 consecutive
      patients prescribed opioids, considered to be receiving stable doses of opioids
      supplemental to their interventional techniques were evaluated for opioid abuse
      and for illicit drug use. Abuse was defined as a patient receiving controlled
      substances from any source other than the prescribing physician at our center
      with the exception of controlled substances for acute injuries unrelated to the
      problem being treated, or for emergencies. Urine drug testing for illicit drugs
      was performed by urine rapid drug screen (Instant Technologies, iCup Norfolk,
      VA). Results were considered positive if one or more of the monitored illicit
      drugs including cocaine, marijuana (THC), phencycledane methamphetamine or
      amphetamines were detected. RESULTS: Opioid abuse was seen in 9% of patients,
      with illicit drug use in 16% of patients. Significant differences were noted in
      the prevalence of opioid abuse in patients who developed chronic pain following
      motor vehicle accident(s) and in patients presenting with pain in three regions
      of the body. Illicit drug use (marijuana) was more common in females. Illicit
      drug use was also more common in patients younger than 45, after motor vehicle
      injury, and in patients with involvement of three regions of the body.
      CONCLUSION: Opioid abuse and illicit drug use were common in chronic pain
      patients with a prevalence of 9% and 16%, respectively. Age, pain after motor
      vehicle accident, involvement of multiple regions and past history of illicit
      drug use were identified as risk factors.

PMID- 16886031
TI  - Pulsed radiofrequency of the dorsal root ganglia is superior to pharmacotherapy
      or pulsed radiofrequency of the intercostal nerves in the treatment of chronic
      postsurgical thoracic pain.
AB  - BACKGROUND: Chronic postsurgical thoracic pain (CPTP) represents a major
      therapeutic challenge characterized by an absence of clinical studies to guide
      treatment. Recently, the implementation of pulsed radiofrequency (RF) has
      generated intense interest in the medical community as a safe and potentially
      effective treatment for neuropathic pain. To date, there are no studies comparing
      pulsed RF to more conventional therapeutic modalities for any pain condition.
      OBJECTIVES: To compare treatment outcomes between pharmacotherapy, pulsed RF of
      the intercostal nerves (ICN) and pulsed RF of the dorsal root ganglia (DRG) in
      CPTP. METHODS: Retrospective data analysis involving 49 patients. RESULTS: At 6
      week follow-up, 61.5% of the pulsed RF DRG group reported > or =50% pain relief
      vs. 27.3% in the medical management (MM) group and 21.4% in the IC group (P =
      0.12). At 3-month follow-up, 53.8% in the DRG group continued to report > or =
      50% pain relief vs. 19.9% in the MM and 6.7% in the ICN groups, respectively (P =
      0.02). Among the pulsed RF patients who did report a successful outcome, the mean
      duration of pain relief was 2.87 months in the ICN group and 4.74 months in the
      DRG group (P = 0.01). CONCLUSIONS: Pulsed RF of the DRG was a superior treatment
      to pharmacotherapy and pulsed RF of the ICN in patients with CPTP. Prospective
      studies are needed to confirm these results and identify the best candidates for
      this treatment.

PMID- 16886032
TI  - Treatment of intractable discogenic low back pain. A systematic review of spinal
      fusion and intradiscal electrothermal therapy (IDET).
AB  - BACKGROUND: A growing number of patients suffer from severe low back pain of
      discogenic origin that is not responsive to conservative medical management.
      These patients must consider the option of surgical spinal fusion or minimally
      invasive intradiscal electrothermal therapy (IDET). OBJECTIVE: To conduct a
      systematic review of clinical outcomes in patients undergoing spinal fusion or
      the intradiscal electrothermal therapy (IDET) procedure for intractable
      discogenic low back pain. DESIGN: Systematic literature review. METHODS: English
      language journal articles published from January 1995 to December 2005 were
      identified through computerized searches of the PubMed database and
      bibliographies of identified articles and review papers. Articles were selected
      if disc degeneration or disruption was the primary indication for spinal fusion
      or the IDET procedure and if follow-up outcome data included evaluations of back
      pain severity, condition-specific functional impairment and/or health-related
      quality of life. The literature reviewed encompassed 33 spinal fusion articles:
      10 randomized controlled trials, 1 nonrandomized controlled trial, 9 before-after
      trials, and 13 case series. There were 18 IDET articles: 2 randomized controlled
      trial, 2 nonrandomized controlled trials, 11 before- after trials, and 3 case
      series. Data were extracted and summarized on patient characteristics, surgical
      methods, and clinical outcomes. RESULTS: Overall, there were similar median
      percentage improvements realized after spinal fusion and the IDET procedure,
      respectively, for 2 of the 3 outcomes evaluated: pain severity (50%, 51%), back
      function (42%, 14%) and quality of life (46%, 43%). There was an identifiable
      randomized controlled trials trend of both treatments reporting a smaller
      magnitude of improvement in all 3 primary outcomes (pain severity, back function,
      quality of life) compared to other types of trials. Perioperative complications
      were commonly associated with spinal fusion (median: 14%, range: 2% to 54%, n =
      31 study groups) whereas adverse events were rarely experienced with the IDET
      procedure (median: 0%, range: 0% to 16%, n = 14 studies). Randomized controlled
      trials of spinal fusion, in particular, had important methodological limitations.
      CONCLUSION: The majority of patients reported improvement in symptoms following
      both spinal fusion and the IDET procedure. The IDET procedure appears to offer
      sufficiently similar symptom amelioration to spinal fusion without the attendant
      complications.

PMID- 16886033
TI  - Feasibility of spinal cord stimulation in a patient with a cardiac pacemaker.
AB  - OBJECTIVE: To report about the safe use of a spinal cord stimulator (SCS) and a
      permanent cardiac pacemaker (PPM). DESIGN: Open-label case report. CASE
      DESCRIPTION: A 75-year-old male with a history of diabetic polyneuropathy and a
      permanent pacemaker was followed for 6 months after implantation of a SCS.
      CONCLUSION: The simultaneous use of bipolar SCS in a patient with a PPM is not
      contraindicated. However, because false inhibition of a cardiac pacemaker may
      potentially lead to serious events, individual testing is mandatory to ascertain
      safety in each patient.

PMID- 16886034
TI  - Partial regeneration of the human hip via autologous bone marrow nucleated cell
      transfer: A case study.
AB  - HISTORY: This is a case report of a 64-year-old white male with a 20 year history
      of unilateral hip pain that had become debilitating over the last several years.
      On intake, Harris hip score was rated as: Pain subscale = 10, Function subscale =
      32, Deformity subscale = 4, Motions subscale = 4.775 with a total score of 50.8
      out of 100. MRI of the affected hip showed severe degeneration with spurring,
      decrease in joint space, and several large subchondral cysts. The patient had
      been evaluated by an orthopedic surgeon and told he was a candidate for bipolar
      hip replacement. METHOD: Two autologous nucleated cell collections were performed
      from bone marrow with subsequent isolation and transfers into the intra-articular
      hip using a hyaluronic acid and thrombin activated platelet rich plasma scaffold.
      Marrow samples were processed by centrifugation and lysis techniques to isolate
      nucleated cells. CONCLUSION: This report describes partial by articular surface
      regeneration 8 weeks after intraarticular bone marrow transfer. Post-op 3.0T FGRE
      MRI showed neocortex formation when compared to immediate pre-op MRI and
      objective improvements were noted that coincided with subjective reports of
      improvement.

PMID- 16886035
TI  - Vertebral augmentation complicated by perioperative addisonian crisis.
AB  - BACKGROUND: We describe a case of perioperative Addisonian crisis induced by
      vertebral augmentation. While several complications of vertebral augmentation
      have been reported previously, related to the technical procedure, to our
      knowledge, perioperative Addisonian crisis from vertebral augmentation has not
      been reported in the literature. OBJECTIVE: To report an Addisonian crisis
      perioperative to vertebral augmentation. DESIGN: Case report. METHOD:
      Retrospective case review. RESULTS: The patient had a history of adrenal
      insufficiency treated previously with steroids. He developed an L3 vertebral
      compression fracture, failed conservative therapy and was eventually referred for
      vertebral augmentation. Immediately after starting the procedure, the patient
      developed profound hypotension unresponsive to intravenous fluids and
      vasopressors, consistent with Addisonian crisis. After intravenous steroids had
      resolved the Addisonian crisis, he underwent vertebral augmentation without
      further complication. CONCLUSION: Addisonian crisis may be triggered by vertebral
      augmentation. Practitioners need to recognize immediately this potentially lethal
      disorder in patients with known or suspected adrenal insufficiency and treat with
      intravenous hydrocortisone.

PMID- 16886036
TI  - Peripheral nerve field stimulation in chronic abdominal pain.
AB  - INTRODUCTION: Spinal Cord Stimulation (SCS) has become an accepted therapeutic
      modality for the treatment of intractable pain syndromes, primarily used today in
      the settings of failed back surgery syndrome, neuropathic back and limb pain. The
      use of spinal cord stimulators for peripheral nerve field electrostimulation is
      becoming increasingly recognized as a safe, effective alternative for chronic
      pain conditions that are refractory to medical management and do not respond to
      traditional dorsal column stimulation. Advances in technology have allowed for
      minimally invasive percutaneous placement of multipolar leads with complex
      programmable systems to provide patient- controlled relief of pain in precisely
      targeted regions. With these improvements in hardware, the use of Peripheral
      Nerve Field Stimulation (PNFS) appears to have an untapped potential for
      providing patients with pain relief for a wider range of underlying conditions
      than was previously believed possible. We present three cases, each with a
      different etiology of chronic abdominal pain: one with inguinal neuralgia, one
      with chronic pancreatitis, and one with pain following liver transplant. Each
      patient was refractory to conventional medical approaches. For all three
      patients, PNFS provided significant relief from pain, enabling patients to
      decrease or discontinue their opioid medications and to enjoy significant
      improvement in their quality of life. We conclude that PNFS is a safe, effective
      and minimally invasive treatment that may be used successfully for a wide variety
      of indications including chronic abdominal pain.

PMID- 16886037
TI  - Vascular uptake of contrast despite negative aspiration in interlaminar cervical
      epidural injection.

PMID- 16886038
TI  - Appearance of plica mediana dorsalis during epidurography.

PMID- 16886040
TI  - Pulsed radiofrequency application for inguinal herniorraphy pain.

PMID- 16886041
TI  - Exploring the Relation Between Memory, Gestural Communication, and the Emergence
      of Language in Infancy: A Longitudinal Study.
AB  - The relationship between recall memory, visual recognition memory, social
      communication, and the emergence of language skills was measured in a
      longitudinal study. Thirty typically developing Swedish children were tested at
      6, 9 and 14 months. The result showed that, in combination, visual recognition
      memory at 6 months, deferred imitation at 9 months and turn-taking skills at 14
      months could explain 41% of the variance in the infants' production of
      communicative gestures as measured by a Swedish variant of the MacArthur
      Communicative Development Inventories (CDI). In this statistical model, deferred
      imitation stood out as the strongest predictor.

PMID- 16886042
TI  - Diagnostic molecular biology.

PMID- 16886045
TI  - Diagnosis of the haemoglobinopathies.
AB  - Despite having been extensively studied at both the biochemical, haematological
      and molecular levels, the haemoglobinopathies continue to provide a diagnostic
      challenge particularly in the multiethnic communities seen in Australia. Early
      detection and characterisation of the haemoglobinopathies is essential so that
      appropriate counselling can be provided to couples and families who may be at
      risk of severe haematological consequences. Although DNA diagnostics have made a
      major impact on our understanding and detection of the haemoglobinopathies, DNA
      mutation testing should never be considered a short cut or the test of first
      choice in the workup of a haemoglobinopathy. A careful three tier approach
      involving: (1) Full blood count (2) Special haematological tests, followed by (3)
      DNA mutation analysis, provides the most effective way in which to detect primary
      gene mutations as well as gene-gene interactions that can influence the overall
      phenotype. Just as important as the laboratory investigations is the family work
      up. Often, the first and most helpful clue to gene gene interactions comes from
      the family study. In Australia, there are many different forms of alpha and beta
      thalassaemia. Increasingly, different Hb Variants are being detected, and their
      effects per se, or in combination with the thalassaemias, provide additional
      diagnostic challenges.

PMID- 16886044
TI  - The influence of cytochrome P450 pharmacogenetics on disposition of common
      antidepressant and antipsychotic medications.
AB  - Since the identification of all the major drug-metabolising cytochrome P450 (CYP)
      enzymes and their major gene variants, pharmacogenetics has had a major impact on
      psychotherapeutic drug therapy. CYP enzymes are responsible for the metabolism of
      most clinically used drugs. Individual variability in CYP activity is an
      important reason for drug therapy failure. Variability in CYP activity may be
      caused by various factors, including endogenous factors such as age, gender and
      morbidity as well as exogenous factors such as co-medication, food components and
      smoking habit. However, polymorphisms, present in most CYP genes, are responsible
      for a substantial part of this variability. Although CYP genotyping has been
      shown to predict the majority of aberrant phenotypes, it is currently rarely
      performed in clinical practice.

PMID- 16886043
TI  - Normal iron metabolism and the pathophysiology of iron overload disorders.
AB  - Iron overload disorders represent a heterogenous group of conditions resulting
      from inherited and acquired causes. If undiagnosed they can be progressive and
      fatal. Early detection and phlebotomy prior to the onset of cirrhosis can reduce
      morbidity and normalise life expectancy. We now have greater insight into the
      complex mechanisms of normal and disordered iron homeostasis following the
      discovery of new proteins and genetic defects. Here we review the normal
      mechanisms and regulation of gastrointestinal iron absorption and liver iron
      transport and their dysregulation in iron overload states. Advances in the
      understanding of the natural history of iron overload disorders and new methods
      for clinical detection and management of hereditary haemochromatosis are also
      reviewed. The current screening strategies target high-risk groups such as first
      degree relatives of affected individuals and those with clinical features
      suggestive of iron loading. Potential ethical, legal and psychosocial issues
      arising through application of genetic screening programs need to be resolved
      prior to implementation of general population screening programs.

PMID- 16886047
TI  - Ethical considerations in the use of DNA for the diagnosis of diseases.
AB  - Scientific advances in genetics have recently provided new information and
      enabled new interventions that are challenging existing ethical conventions. ISO
      15189:20031 obliges the laboratory to consider its ethical responsibilities and
      the AACB (through membership of the IFCC) has taken a leading role in the
      discussion of evolving new ethical frameworks. This paper discusses the ethical
      implication of many of these recent advances in genetics and highlights some of
      the still unresolved ethical issues.

PMID- 16886046
TI  - Clinical applications of molecular biology for infectious diseases.
AB  - Molecular biological methods for the detection and characterisation of
      microorganisms have revolutionised diagnostic microbiology and are now part of
      routine specimen processing. Polymerase chain reaction (PCR) techniques have led
      the way into this new era by allowing rapid detection of microorganisms that were
      previously difficult or impossible to detect by traditional microbiological
      methods. In addition to detection of fastidious microorganisms, more rapid
      detection by molecular methods is now possible for pathogens of public health
      importance. Molecular methods have now progressed beyond identification to detect
      antimicrobial resistance genes and provide public health information such as
      strain characterisation by genotyping. Treatment of certain microorganisms has
      been improved by viral resistance detection and viral load testing for the
      monitoring of responses to antiviral therapies. With the advent of multiplex PCR,
      real-time PCR and improvements in efficiency through automation, the costs of
      molecular methods are decreasing such that the role of molecular methods will
      further increase. This review will focus on the clinical utility of molecular
      methods performed in the clinical microbiology laboratory, illustrated with the
      many examples of how they have changed laboratory diagnosis and therefore the
      management of infectious diseases.

PMID- 16886048
TI  - Genotyping of single nucleotide substitutions.
AB  - The description of the polymerase chain reaction in 1985 caused a revolution in
      genetics and today molecular diagnostics is one of the leading growth areas
      across all disciplines of laboratory medicine. This paper reviews the principles
      and limitations of a number of traditional and emerging techniques for typing of
      single nucleotide substitutions. The techniques discussed include traditional
      approaches such as restriction enzyme analysis, more recent homogenous methods,
      such as those utilising TaqMan, fluorescence resonance energy transfer (FRET) and
      Scorpion probes, and high resolution melting curve analysis. Non-homogenous but
      highly flexible approaches such as Pyrosequencing and mass-spectrometry are also
      discussed. While many techniques are available, it is clear that no one approach
      is clearly superior. However, in terms of their many advantages and continuing
      developments, homogenous approaches have much to recommend them.

PMID- 16886049
TI  - The Clinical Research Forum and Association of American Physicians disagree with
      criticism of the NIH Roadmap.
AB  - As representatives of 50 leading academic medical centers focusing on clinical
      research and many of academic medicine's scientific leaders, the Clinical
      Research Forum and Association of American Physicians disagree with the JCI's
      recent editorials on the NIH Roadmap, Elias Zerhouni's leadership, and the future
      directions of biomedical research.

PMID- 16886051
TI  - Gout: new insights into an old disease.
AB  - Gout is an autoinflammatory disorder associated with deposition of monosodium
      urate (MSU) crystals in joints and periarticular tissues. Recent advances suggest
      that the innate immune system may drive the gouty inflammatory response to MSU.
      These findings prompt questions concerning how the innate immune system
      recognizes MSU and the identities of the receptors involved. In this issue of the
      JCI, Chen et al. show that the IL-1 receptor and its signaling protein myeloid
      differentiation primary response protein 88 (MyD88) but not the "classical"
      innate immune receptors, TLRs, are central for MSU-induced inflammation (see the
      related article beginning on page 2262).

PMID- 16886052
TI  - What's in a name? eNOS and anaphylactic shock.
AB  - In this issue of the JCI, a study by Cauwels and colleagues suggests a central
      role for eNOS, the endothelial isoform of nitric oxide synthase, as a mediator of
      anaphylaxis (see the related article beginning on page 2244). Why is an enzyme
      originally described as a physiological mediator of vascular homeostasis
      implicated in the spectacular vascular collapse that is characteristic of
      anaphylaxis? And is the eNOS involved in anaphylaxis necessarily exerting its
      effect solely in the vascular endothelium, or might this "endothelial enzyme"
      actually be playing a more fundamental role in an entirely different tissue?
      After all, what's in a name?

PMID- 16886053
TI  - HIV and CXCR4 in a kiss of autophagic death.
AB  - AIDS is characterized by CD4+ T lymphocyte depletion, yet the mechanisms
      underlying this central aspect of HIV pathogenesis are still poorly understood.
      In this issue of the JCI, Espert et al. identify a mechanism by which the HIV
      envelope glycoprotein can induce death in uninfected CD4+ T cells (see the
      related article beginning on page 2161). The HIV envelope glycoprotein interacts
      with CXC chemokine receptor 4 to activate the lysosomal degradation pathway of
      autophagy, which is necessary for both apoptotic and nonapoptotic cell death.

PMID- 16886050
TI  - Resurrection of vitamin D deficiency and rickets.
AB  - The epidemic scourge of rickets in the 19th century was caused by vitamin D
      deficiency due to inadequate sun exposure and resulted in growth retardation,
      muscle weakness, skeletal deformities, hypocalcemia, tetany, and seizures. The
      encouragement of sensible sun exposure and the fortification of milk with vitamin
      D resulted in almost complete eradication of the disease. Vitamin D (where D
      represents D2 or D3) is biologically inert and metabolized in the liver to 25
      hydroxyvitamin D [25(OH)D], the major circulating form of vitamin D that is used
      to determine vitamin D status. 25(OH)D is activated in the kidneys to 1,25
      dihydroxyvitamin D [1,25(OH)2D], which regulates calcium, phosphorus, and bone
      metabolism. Vitamin D deficiency has again become an epidemic in children, and
      rickets has become a global health issue. In addition to vitamin D deficiency,
      calcium deficiency and acquired and inherited disorders of vitamin D, calcium,
      and phosphorus metabolism cause rickets. This review summarizes the role of
      vitamin D in the prevention of rickets and its importance in the overall health
      and welfare of infants and children.

PMID- 16886054
TI  - Costimulation couture: a designer approach to regulating autoimmunity.
AB  - Negative or inhibitory costimulatory pathways regulate T cell activation and play
      a role in peripheral tolerance. Targeting these pathways harnesses the
      physiologic mechanisms of regulating autoimmunity and could prove beneficial for
      the therapy of autoimmune diseases. However, attempts at targeting these pathways
      have been fraught with difficulties. In this issue of the JCI, Fife et al.
      describe a creative approach for targeting CTL-associated antigen 4 (CTLA-4) on
      activated T cells via genetically engineered B cells to prevent autoimmune
      diabetes in the NOD mouse (see the related article beginning on page 2252). Novel
      "designer" strategies targeting negative costimulatory pathways provide reasons
      for optimism in the search for a cure for devastating autoimmune diseases.

PMID- 16886055
TI  - Misbehaving macrophages in the pathogenesis of psoriasis.
AB  - Psoriasis is a chronic inflammatory skin disease unique to humans. In this issue
      of the JCI, 2 studies of very different mouse models of psoriasis both report
      that macrophages play a key role in inducing psoriasis-like skin disease.
      Psoriasis is clearly a polygenic, inherited disease of uncontrolled cutaneous
      inflammation. The debate that currently rages in the field is whether psoriasis
      is a disease of autoreactive T cells or whether it reflects an intrinsic defect
      within the skin--or both. However, these questions have proven difficult to
      dissect using molecular genetic tools. In the current studies, the authors have
      used 2 different animal models to address the role of macrophages in disease
      pathogenesis: Wang et al. use a mouse model in which inflammation is T cell
      dependent, whereas the model used by Stratis et al. is T cell independent (see
      the related articles beginning on pages 2105 and 2094, respectively). Strikingly,
      both groups report an important contribution by macrophages, implying that
      macrophages can contribute to both epithelial-based and T cell-mediated pathways
      of inflammation.

PMID- 16886056
TI  - Tuning the oviduct to the anandamide tone.
AB  - Anandamide (N-arachidonoylethanolamide) is a lipid signal molecule that was the
      first endogenous agonist for cannabinoid receptors to be discovered. Cannabinoid
      receptor type 1 (CB1) is widely distributed in neurons and nonneuronal cells in
      brain and peripheral organs including sperm, eggs, and preimplantation embryos. A
      study by Wang and colleagues in this issue of the JCI demonstrates that a
      critical balance between anandamide synthesis by N-acylphosphatidylethanolamine
      selective phospholipase D (NAPE-PLD) and its degradation by fatty acid amide
      hydrolase (FAAH) in mouse embryos and oviducts creates locally an appropriate
      "anandamide tone" required for normal embryo development, oviductal transport,
      implantation, and pregnancy (see the related article beginning on page 2122).
      Adverse effects of elevated levels of anandamide on these processes resulting
      from FAAH inactivation are mimicked by administration of (-)-Delta9
      tetrahydrocannabinol (THC; the major psychoactive constituent of marijuana), due
      to enhanced signaling via CB1. These findings show that exogenous THC can swamp
      endogenous anandamide signaling systems, thereby affecting multiple physiological
      processes.

PMID- 16886057
TI  - The glomerular basement membrane: not gone, just forgotten.
AB  - The glomerular capillaries function as the filtration barrier that retains
      albumin and other plasma proteins in the circulation. The unresolved question
      that has been asked for more than 50 years is, Which structural component of
      these capillaries constitutes the main molecular sieve that normally retains
      albumin and allows its passage in diseases associated with proteinuria? There is
      considerable evidence implicating both the glomerular basement membrane (GBM) and
      the epithelial filtration slits as the barrier. However, the prevailing point of
      view at present is that the slit diaphragms bridging the filtration slits are
      responsible for this important function, and evidence implicating the GBM is
      largely ignored or forgotten. In this issue of the JCI, Jarad et al. show that in
      laminin beta2-deficient (Lamb2-/-) mice, proteinuria can be directly attributed
      to the altered composition of the GBM (see the related article beginning on page
      2272). Changes in the permeability of the GBM and its organization were primary
      to changes in the epithelium, as they preceded foot process effacement and loss
      of slit diaphragms.

PMID- 16886058
TI  - Pathogenic role for skin macrophages in a mouse model of keratinocyte-induced
      psoriasis-like skin inflammation.
AB  - Psoriasis is a common skin disease, the pathogenesis of which has not yet been
      resolved. In mice, epidermis-specific deletion of inhibitor of NF-kappaB
      (IkappaB) kinase 2 (IKK2) results in a skin phenotype that mimics human psoriasis
      in several aspects. Like psoriasis, this skin disease shows pronounced
      improvement when mice are treated with a TNF-neutralizing agent. We have found
      previously that this phenotype does not depend on the presence of alphabeta T
      lymphocytes. In order to evaluate contributions of other immune cell populations
      to the skin disease, we selectively eliminated macrophages and granulocytes from
      the skin of mice with epidermis-specific deletion of IKK2 (K14-Cre-IKK2fl/fl
      mice). Elimination of skin macrophages by subcutaneous injection of clodronate
      liposomes was accompanied by inhibition of granulocyte migration into the skin
      and resulted in a dramatic attenuation of psoriasis-like skin changes. The
      hyperproliferative, inflammatory skin disease in K14-Cre-IKK2fl/fl mice was a
      direct consequence of the presence of macrophages in the skin, as targeted
      deletion of CD18, which prevented accumulation of granulocytes but not
      macrophages, did not lead to major changes in the phenotype. Targeted deletion of
      the receptor for IFN-gamma revealed that the pathogenesis of the skin disease
      does not depend on classical IFN-gamma-mediated macrophage activation. Our
      results demonstrate that in mice epidermal keratinocytes can initiate a
      hyperproliferative, inflammatory, IFN-gamma-independent, psoriasis-like skin
      disease whose development requires essential contributions from skin macrophages
      but not from granulocytes or alphabeta T lymphocytes.

PMID- 16886059
TI  - Activated macrophages are essential in a murine model for T cell-mediated chronic
      psoriasiform skin inflammation.
AB  - The CD18 hypomorphic (CD18hypo) PL/J mouse model clinically resembling human
      psoriasis is characterized by reduced expression of the common chain of beta2
      integrins (CD11/CD18) to only 2-16% of WT levels. Previously we found that this
      chronic psoriasiform skin inflammation also depends on the presence of CD4+ T
      cells. Herein we investigated the role of macrophages in this CD18hypo mouse
      model. Activated macrophages were significantly increased in lesional skin as
      well as in inflamed skin draining lymph nodes (DLNs) of affected CD18hypo mice
      and were identified as being an important source of TNF-alpha in vivo. Both
      depletion of macrophages and neutralization of TNF-alpha resulted in a
      significant alleviation of psoriasiform skin inflammation. As monocyte
      chemotactic protein 1 was enhanced in lesional skin of affected CD18hypo mice, we
      intradermally injected recombinant murine monocyte chemotactic protein-1 (rJE/MCP
      1) alone or in combination with rTNF-alpha into the skin of healthy CD18hypo
      mice. Only simultaneous injection of rJE/MCP-1 and rTNF-alpha, but neither
      substance alone, resulted in the induction of psoriasiform skin inflammation
      around the injection sites with recruitment and activation of macrophages.
      Collectively, our data suggest that maintenance of psoriasiform skin inflammation
      critically depends on efficient recruitment and activation of macrophages with
      sufficient release of TNF-alpha.

PMID- 16886060
TI  - Fatty acid amide hydrolase deficiency limits early pregnancy events.
AB  - Synchronized preimplantation embryo development and passage through the oviduct
      into the uterus are prerequisites for implantation, dysregulation of which often
      leads to pregnancy failure in women. Cannabinoid/endocannabinoid signaling via
      cannabinoid receptor CB1 is known to influence early pregnancy. Here we provide
      evidence that a critical balance between anandamide synthesis by N
      acylphosphatidylethanolamine-selective phospholipase D (NAPE-PLD) and its
      degradation by fatty acid amide hydrolase (FAAH) in mouse embryos and oviducts
      creates locally an appropriate "anandamide tone" for normal development of
      embryos and their oviductal transport. FAAH inactivation yielding higher
      anandamide or experimentally induced higher cannabinoid [(-)-Delta9
      tetrahydrocannabinol] levels constrain preimplantation embryo development with
      aberrant expression of Cdx2, Nanog, and Oct3/4, genes known to direct lineage
      specification. Defective oviductal embryo transport arising from aberrant
      endocannabinoid signaling also led to deferred on-time implantation and poor
      pregnancy outcome. Intercrossing between wild-type and Faah-/- mice rescued
      developmental defects, not oviductal transport, implying that embryonic and
      maternal FAAH plays differential roles in these processes. The results suggest
      that FAAH is a key metabolic gatekeeper, regulating on-site anandamide tone to
      direct preimplantation events that determine the fate of pregnancy. This study
      uncovers what we believe to be a novel regulation of preimplantation processes,
      which could be clinically relevant for fertility regulation in women.

PMID- 16886061
TI  - Autophagy is involved in T cell death after binding of HIV-1 envelope proteins to
      CXCR4.
AB  - HIV-1 envelope glycoproteins (Env), expressed at the cell surface, induce
      apoptosis of uninfected CD4+ T cells, contributing to the development of AIDS.
      Here we demonstrate that, independently of HIV replication, transfected or HIV
      infected cells that express Env induced autophagy and accumulation of Beclin 1 in
      uninfected CD4+ T lymphocytes via CXCR4. The same phenomena occurred in a T cell
      line and in transfected HEK.293 cells that expressed both wild-type CXCR4 and a
      truncated form of CD4 that is unable to bind the lymphocyte-specific protein
      kinase Lck. Env-mediated autophagy is required to trigger CD4+ T cell apoptosis
      since blockade of autophagy at different steps, by either drugs (3-methyladenine
      and bafilomycin A1) or siRNAs specific for Beclin 1/Atg6 and Atg7 genes, totally
      inhibited the apoptotic process. Furthermore, CD4+ T cells still underwent Env
      mediated cell death with autophagic features when apoptosis was inhibited. These
      results suggest that HIV-infected cells can induce autophagy in bystander CD4+ T
      lymphocytes through contact of Env with CXCR4, leading to apoptotic cell death, a
      mechanism most likely contributing to immunodeficiency.

PMID- 16886062
TI  - Anaphylactic shock depends on PI3K and eNOS-derived NO.
AB  - Anaphylactic shock is a sudden, life-threatening allergic reaction associated
      with severe hypotension. Platelet-activating factor (PAF) is implicated in the
      cardiovascular dysfunctions occurring in various shock syndromes, including
      anaphylaxis. Excessive production of the vasodilator NO causes inflammatory
      hypotension and shock, and it is generally accepted that transcriptionally
      regulated inducible iNOS is responsible for this. Nevertheless, the contribution
      of NO to PAF-induced shock or anaphylactic shock is still ambiguous. We studied
      PAF and anaphylactic shock in conscious mice. Surprisingly, hyperacute PAF shock
      depended entirely on NO, produced not by inducible iNOS, but by constitutive
      eNOS, rapidly activated via the PI3K pathway. Soluble guanylate cyclase (sGC) is
      generally regarded as the principal vasorelaxing mediator of NO. Nevertheless,
      although methylene blue partially prevented PAF shock, neither 1H
      [1,2,4]oxadiazole[4,3-a]quinoxalin-1-one (ODQ) nor sGCalpha1 deficiency did.
      Also, in 2 different models of active systemic anaphylaxis, inhibition of NOS,
      PI3K, or Akt or eNOS deficiency provided complete protection. In contrast to the
      unsubstantiated paradigm that only excessive iNOS-derived NO underlies
      cardiovascular collapse in shock, our data strongly support the unexpected
      concept that eNOS-derived NO is the principal vasodilator in anaphylactic shock
      and define eNOS and/or PI3K or Akt as new potential targets for treating
      anaphylaxis.

PMID- 16886063
TI  - Inhibition of T cell activation and autoimmune diabetes using a B cell surface
      linked CTLA-4 agonist.
AB  - CTL-associated antigen 4 (CTLA-4) engagement negatively regulates T cell
      activation and function and promotes immune tolerance. However, it has been
      difficult to explore the biology of selective engagement of CTLA-4 in vivo
      because CTLA-4 shares its ligands, B7-1 and B7-2, with CD28. To address this
      issue, we developed a Tg mouse expressing a single-chain, membrane-bound anti
      CTLA-4 Ab (scFv) on B cells. B and T cells developed normally and exhibited
      normal phenotype in the steady state and after activation in these mice. However,
      B cells from scFv Tg+ mice (scalphaCTLA4+) prevented T cell proliferation and
      cytokine production in mixed lymphocyte reactions. Additionally, mice treated
      with scalphaCTLA4+ B cells had decreased T cell-dependent B cell Ab production
      and class switching in vivo after antigen challenge. Furthermore, expression of
      this CTLA-4 agonist protected NOD mice from spontaneous autoimmune diabetes.
      Finally, this disease prevention occurred in Treg-deficient NOD.B7-1/B7-2 double
      knockout mice, suggesting that the effect of the CTLA-4 agonist directly
      attenuates autoreactive T cell activation, not Treg activation. Together, results
      from this study demonstrate that selective ligation of CTLA-4 attenuates in vivo
      T cell responses, prevents development of autoimmunity, and represents a novel
      immunotherapeutic approach for the induction and maintenance of peripheral
      tolerance.

PMID- 16886064
TI  - MyD88-dependent IL-1 receptor signaling is essential for gouty inflammation
      stimulated by monosodium urate crystals.
AB  - While it is known that monosodium urate (MSU) crystals cause the disease gout,
      the mechanism by which these crystals stimulate this inflammatory condition has
      not been clear. Here we find that the Toll/IL-1R (TIR) signal transduction
      adaptor myeloid differentiation primary response protein 88 (MyD88) is required
      for acute gouty inflammation. In contrast, other TIR adaptor molecules,
      TIRAP/Mal, TRIF, and TRAM, are not required for this process. The MyD88-dependent
      TLR1, -2, -4, -6, -7, -9, and -11 and IL-18 receptor (IL-18R) are not essential
      for MSU-induced inflammation. Moreover, MSU does not stimulate HEK cells
      expressing TLR1-11 to activate NF-kappaB. In contrast, mice deficient in the
      MyD88-dependent IL-1R showed reduced inflammatory responses, similar to those
      observed in MyD88-deficient mice. Similarly, mice treated with IL-1 neutralizing
      antibodies also showed reduced MSU-induced inflammation, demonstrating that IL-1
      production and IL-1R activation play essential roles in MSU-triggered
      inflammation. IL-1R deficiency in bone marrow-derived cells did not affect the
      inflammatory response; however, it was required in non-bone marrow-derived cells.
      These results indicate that IL-1 is essential for the MSU-induced inflammatory
      response and that the requirement of MyD88 in this process is primarily through
      its function as an adaptor molecule in the IL-1R signaling pathway.

PMID- 16886066
TI  - Optical resolution methods.
AB  - Despite the large number of elaborate enantioselective syntheses for the
      preparation of a single enantiomer to achieve industrial and scientific goals,
      the separation and purification of enantiomers (components of racemic compounds)
      is also necessary. Hence, we present the most often used thought-provoking modern
      methods based on momentous recognitions (e.g. spontaneous resolution, induced
      crystallization, resolution by formation of diastereomers, resolution by
      formation of non-covalent diastereomers, resolution by diastereomeric salt
      formation, resolution by diastereomeric complex formation, "half equivalent"
      methods of resolution, separation by crystallization, separation by distillation,
      separation by supercritical fluid extraction, resolution with mixtures of
      resolving agents, resolution with a derivative of the target compound,
      enantioselective chromatography, resolution by formation of covalent
      diastereomers, resolution by substrate selective reaction, kinetic resolution
      without enzymes, kinetic resolution by enzyme catalysis, hydrolytic and redox
      enzymes, kinetic and thermodynamic control, resolutions combined with 2nd order
      asymmetric transformations, enrichment of partially resolved mixtures, role of
      the solvent and methods of optimization in the separation of diastereoisomers,
      non-linear effects and selected examples of resolution on an industrial scale).

PMID- 16886067
TI  - Synthetic functional pi-stack architecture in lipid bilayers.
AB  - Neglected until recently, pi-stack architecture is rapidly emerging as a powerful
      strategy to create function in lipid bilayer membranes. Recent reports describe
      supramolecular rosettes acting as hosts of intercalating guests, to assemble in
      bilayer membranes and, in the case of stacked guanosine and folate quartets, to
      form ion channels. The introduction of rigid-rod pi-stack architecture allowed us
      to address one of the great challenges in the field, i.e. ligand gating.
      Inspiring pi-stack chemistry from related fields, covering rainbow coloration,
      conductivity, as well as the critical dependence of charge mobilities on the
      precision of supramolecular organization is summarized to zoom in on arguably the
      most promising application of functional pi-stack architecture in lipid bilayers,
      that is the creation of multifunctional photosystems.

PMID- 16886065
TI  - Proteinuria precedes podocyte abnormalities inLamb2-/- mice, implicating the
      glomerular basement membrane as an albumin barrier.
AB  - Primary defects in either podocytes or the glomerular basement membrane (GBM)
      cause proteinuria, a fact that complicates defining the barrier to albumin.
      Laminin beta2 (LAMB2) is a GBM component required for proper functioning of the
      glomerular filtration barrier. To investigate the GBM's role in glomerular
      filtration, we characterized GBM and overlying podocyte architecture in relation
      to development and progression of proteinuria in Lamb2-/- mice, which model
      Pierson syndrome, a rare congenital nephrotic syndrome. We found ectopic
      deposition of several laminins and mislocalization of anionic sites in the GBM,
      which together suggest that the Lamb2-/- GBM is severely disorganized, although
      it is ultrastructurally intact. Importantly, albuminuria was detectable shortly
      after birth and preceded podocyte foot process effacement and loss of slit
      diaphragms by at least 7 days. Expression and localization of slit diaphragm and
      foot process-associated proteins appeared normal at early stages. GBM
      permeability to the electron-dense tracer ferritin was dramatically elevated in
      Lamb2-/- mice, even before widespread foot process effacement. Increased ferritin
      permeability was not observed in nephrotic CD2-associated protein-null (Cd2ap-/-)
      mice, which have a primary podocyte defect. Together these data show that the GBM
      serves as a barrier to protein in vivo and that the glomerular slit diaphragm
      alone is not sufficient to prevent the passage of albumin into the urinary space.

PMID- 16886068
TI  - Variations of the P2 group in HIV-1 protease inhibitors containing a tertiary
      alcohol in the transition-state mimicking scaffold.
AB  - A short synthetic protocol leading to HIV-1 protease inhibitors with a tertiary
      alcohol based transition-state mimicking unit and different P2 side chains has
      been developed.

PMID- 16886069
TI  - Synthesis and crystal structure of [2 + 2] calixsalens.
AB  - Efficient synthesis of chiral [2 + 2] macrocyclic tetraimines which display
      calixarene-like crystal structures has been described, with short reaction times
      under microwave irradiation.

PMID- 16886070
TI  - A diastereoselective and concise synthesis of functionalised vinyl epoxides with
      a Morita-Baylis-Hillman backbone.
AB  - A highly diastereoselective organocatalytic synthesis of unique functionalised
      vinyl epoxides, displaying a Morita-Baylis-Hillman backbone, has been developed
      by means of an user friendly sulfonium ylide epoxidation of aldehydes from a
      readily available alpha-(bromomethyl)acrylamide derivative. The first result in
      the asymmetric version is discussed.

PMID- 16886071
TI  - Geometry in digital molecular arrays.
AB  - The development of digital molecular devices arises through the appropriate
      geometric positioning of a molecular assay. A detailed evaluation of the digital
      media reveals the critical aspects of geometric positioning in terms of
      developing an analytically-robust system for molecular analysis. This study
      reveals an explicit digital compact disc based assay for molecular affinity
      events.

PMID- 16886072
TI  - Syntheses, pi-stacking interactions and base-pairings of uracil pyridinium salts
      and uracilyl betaines with nucleobases.
AB  - Reaction of 6-chlorouracil with 4-(dimethylamino)pyridine, 4-methylpyridine, and
      pyridin-4-yl-morpholine yielded pyridinium-substituted uracils as chlorides which
      were converted into pyridinium uracilates by deprotonation. These heterocyclic
      mesomeric betaines are cross-conjugated and thus possess separate cationic
      (pyridinium) and anionic (uracilate) moieties. Calculations and X-ray single
      crystal analyses were performed in order to characterize these systems and to
      compare the salts with the betaines. (1)H NMR experiments in D(2)O proved pi
      interactions between the uracilyl betaines and adenine, adenosine, as well as
      adeninium. No pi-stacking interactions were detected between the betaines and
      guanosine. The acidic N8-H group of the uracil pyridinium salts caused acid-base
      reactions which were observed in parallel to pi-stacking interactions. Self
      complementarity of the modified uracils was detected by (1)H NMR experiments in
      DMSO-d(6) and electrospray ionisation mass spectrometry (ESIMS). Ab initio
      calculations predicted base-pairings of the modified uracils with adeninium,
      cytosine, and guanine. Several geometries of hydrogen-bonded associates were
      calculated. Hoogsteen pairings between the uracil-4-(dimethylamino)pyridinium
      salt and adeninium, as well as associates between the corresponding betaine plus
      cytosine, and the betaine plus guanine were calculated, and the most stable
      conformations were determined. In the ESI mass spectra, prominent peaks of
      associates between the modified uracils and adeninium, cytosine, cytidine,
      guanosine and d(CpGp) were detected.

PMID- 16886073
TI  - New propranolol analogues: binding and chiral discrimination by cellobiohydrolase
      Cel7A.
AB  - Novel propranolol analogues have been designed and synthesised and their
      enantioselective binding to the cellulose degrading enzyme, Cel7A, has been
      evaluated. Affinity and enantioselectivity have been determined by capillary
      electrophoresis experiments. Ligands with significantly improved affinity and
      selectivity have been obtained and an analysis of the results has led to insights
      concerning the relation between the changes in ligand structure and selectivity
      as well as affinity to the protein.

PMID- 16886074
TI  - Sterically crowded azulene-based dication salts as novel guests: synthesis and
      complexation studies with crown ethers and calixarenes in solution and in the gas
      phase.
AB  - The 1,4-bis(3-guaiazulenylmethylium)benzene and 1,4-bis[1-(4,6,8
      trimethylazulenylmethylium)]benzene dication salts were synthesized via an acid
      catalyzed condensation/dehydration protocol with guaiazulene-terephthalaldehyde
      (2 : 1 ratio), and 4,6,8-trimethylazulene-terephthalaldehyde (2 : 1 ratio)
      respectively in one-pot processes. A similar condensation reaction with the
      parent azulene led to an insoluble oligomer that was shown by MALDI-TOF-MS to
      contain 1,4-bis[(diazulenyl)methylium]benzene as a repeating unit. Dication salts
      and were fully characterized by 2D NMR and NOE techniques and by electrospray-MS
      (ES-MS) and MALDI-TOF-MS. NMR studies confirm that the dications are best
      represented as bis-tropylium species. A delicate balance of electronic (inductive
      stabilization) and steric influence of the alkyl groups on the seven-membered
      ring seems to influence the chemo-/regioselectivity of the co-condensation
      process. NMR titration and T(1) measurements established that, despite its highly
      crowded structure, dication forms host-guest HG complexes with dibenzo-30-crown
      10 (DB30C10) and dibenzo-24-crown-8 (DB24C8) in solution, but fails to complex
      with the smaller dibenzo-18-crown-6 (DB18C6). The corresponding HG cation
      molecule cluster ions were also detected in the gas phase by ES-MS, showing the
      formation of both dication-crown 1 : 1 and 1 : 2 complexes. Similar complexation
      of dication salt with DB30C10 was observed via NMR titration and T(1)
      measurements in solution and by ES-MS in the gas phase. Although solution
      complexation studies (NMR titration) did not indicate stable complex formation
      between and p-tert-butyl-methoxycalix[8]arene, their [HG](2+) and [H(2)G](2+)
      clusters were detectable by ES-MS. Solution decomplexation experiments (HG(2+) -
      > H + G(2+)) were performed on -crown complex by addition of DMSO, acetone,
      silver tosylate, and tropylium cation salt. Complexation of with DB30C10 was also
      studied by microcalorimetric titration.

PMID- 16886076
TI  - Theoretical models of directional proton molecular transport.
AB  - The important topic of proton transport through molecular wires is usually
      associated with the Grotthuss mechanism. In this paper we propose an alternative
      conductor based on chains of lone pairs. B3LYP/6-31+G** and PW91 DFT calculations
      on model compounds (1,2,3,4-tetrasubstituted benzenes) show that these compounds
      could play the role of proton conductors.

PMID- 16886075
TI  - Transannular pi-pi interactions in janusenes and in related rigid systems with
      cofacial aromatic rings; gauging aromaticity in the hydrocarbons and in model
      carbocations; a DFT study.
AB  - The utility of NICS (nuclear independent chemical shift) as a probe for
      detecting/sensing variation in aromaticity due to transannular pi-pi interactions
      in janusene , a [3.3]orthocyclophane having two cofacial benzene rings within van
      der Waals distance, its tetrafluoro- and octafluoro-derivatives and , and in
      tropiliojanusene was studied by DFT at the B3LYP/6-31G(d) level. The related
      hydrocarbons and with a buried double-bond and their carbocations were also
      included in this study. Whereas NICS(0) and NICS(1) are rather insensitive to
      transannular interactions, computed NICS(1)(zz), values are larger and more
      negative for both pi-decks in the interannular space and this is consistent with
      increased transannular pi-pi interactions in the cofacial rings, previously shown
      in these systems via spectroscopic studies (UV and NMR), and by electrophilic
      chemistry. Transannular effects in , , and were also probed by examining the
      forms of HOMO-LUMOs. Attempts to measure donor-accepter interactions between
      electron rich/electron poor cofacial decks via NICS (1)(zz) through substituent
      effects proved unsuccessful, resulting in only very small changes. Protonation of
      the double-bond buried in between the two pi-decks in and results in internally
      pi-stabilized carbocations that exhibit more negative NICS(1) and NICS(1)(zz)
      values in the interannular space. GIAO NMR data were computed for the neutral
      hydrocarbons and their derived carbocations, as a guiding tool for planned
      experimental studies.

PMID- 16886077
TI  - Diphenylphosphinoyl-mediated synthesis of ketones.
AB  - alpha-Diphenylphosphinoyl ketones are selectively and sequentially alkylated at
      the alpha-position. Double lithiation and selective alkylation occurs at the less
      stabilised gamma-position. Dephosphinoylation of the alkylation products gives
      ketones. Mono-alkylation is selective, highly crystalline intermediates are
      formed and a one-pot strategy is possible. The method is ideally suited for the
      preparation of acid-sensitive ketones.

PMID- 16886078
TI  - Asymmetric synthesis of cyclopropanes and dihydrofurans based on phosphine oxide
      chemistry.
AB  - The asymmetric synthesis of gamma-azido trans-cyclopropyl ketones is accomplished
      via a short, simple and efficient sequence. The cyclopropanation step is achieved
      by an intramolecular nucleophilic ring closure, with a diphenylphosphinate
      leaving group, to give trans-cyclopropane exclusively. beta-Keto
      diphenylphosphine oxides cyclise to form optically active dihydrofurans. All
      possible diastereoisomers of dihydrofurans can be prepared selectively starting
      from the same olefin.

PMID- 16886080
TI  - Diphenylphosphinoyl chloride as a chlorinating agent--the selective double
      activation of 1,2-diols.
AB  - Treatment of 1,2-diols with diphenylphosphinoyl chloride in pyridine produces
      beta-chloroethyl phosphinates which react with complete control of
      stereochemistry to give epoxides and azido-alcohols, useful intermediates in
      cyclopropane synthesis.

PMID- 16886079
TI  - Asymmetric synthesis of orthogonally protected trans-cyclopropane gamma-amino
      acids via intramolecular ring closure.
AB  - The synthesis of enantiomerically-enriched trans-cyclopropane amino- and hydroxy
      acids can be achieved by intramolecular ring closure in moderate to good yields.
      The optically active cyclopropane precursors are easily prepared in a short
      sequence from inexpensive, commercially available olefins and tert-butyl acetate.
      Several leaving groups and bases were compared for the cyclopropanation step,
      showing that the diphenylphosphinate and tosyl leaving groups give the best
      results when used in combination with either LDA or NaHMDS.

PMID- 16886081
TI  - Episulfonium ion-mediated cyclic peptide and triazine synthesis.
AB  - The product of an episulfonium ion-mediated cyclotrimerisation, previously
      reported as being a 15-membered ring trilactam, has now been shown to be a 1,3,5
      triazine. Smaller medium-ring bilactams have, however, been synthesised from
      linear precursors using the sulfur-based methodology.

PMID- 16886082
TI  - N-Hydroxy and N-acyloxy peptides: synthesis and chemical modifications.
AB  - The preparation of a series of N-hydroxy peptides is described, along with their
      acylation on the oxygen of the pseudopeptide bond. Nineteen N-acyloxy peptides,
      first examples of this new class of pseudopeptides, were thus synthesized; they
      present a range of acyl groups, including N-protected amino acyl groups.
      Possibilities of elongation for these pseudopeptides were also investigated.

PMID- 16886083
TI  - Microwave-assisted cyclic amidine synthesis using TiCl4.
AB  - Microwave-assisted treatment of various heterocyclic amides (benzodiazepinone,
      phthalazone) with TiCl(4) in the presence of primary or secondary amines provides
      the corresponding amidines. In addition to the interest of the microwaves for
      this reaction, our study highlights the higher reactivity of the cyclic acetamide
      moiety compared to the cyclic benzamide moiety towards this TiCl(4)-mediated
      reaction.

PMID- 16886084
TI  - Avidin and streptavidin ligands based on the glycoluril bicyclic system.
AB  - Glycoluril derivatives with a carboxylic acid side chain have been synthesized
      and shown to bind to both avidin and streptavidin. Introduction of a valerate
      side chain in glycoluril led to an increased binding to both proteins only when
      the valerate group was bound to a N atom and with the proper stereochemistry [(+)
      enantiomer]. On the other hand, introduction of the valerate side chain either on
      the bridgehead carbon or on the N atom with the opposite stereochemistry [(-)
      enantiomer] led to a decrease in binding constant compared with unsubstituted
      glycoluril. Direct spectrophotometric competitive titration of each protein with
      a racemic ligand allowed measurement of the enantioselectivity of the ligand
      protein complexation, together with the binding constant of the two enantiomers.
      In the case of the N-substituted glycoluril, the extension of the side chain by
      one methylene group, from valerate to caproate, led to an increase in the binding
      constant to both proteins. Docking studies using AutoDock 3.05 have been
      performed in order to predict the binding modes of these ligands to streptavidin.
      The effect of the stereochemistry and the position of the side chain on the
      binding constant to streptavidin is discussed in view of the predicted binding
      modes.

PMID- 16886085
TI  - Intramolecular 1,3-dipolar cycloadditions of dihydroimidazolium ylides: synthesis
      of pyrrolo[1,2,3-de]quinoxalines and imidazo[1,2-a]indoles.
AB  - N-Alkylation of 4,5-dihydroimidazoles with alkene-containing bromomethyl ketones
      and treatment of the so-formed 4,5-dihydroimidazolium ions with DBU gives rise to
      an intramolecular 1,3-dipolar cycloaddition reaction that affords (via a reaction
      cascade involving eliminative ring-opening, recyclisation and prototropic
      tautomerism) unexpected hexahydropyrrolo[1,2,3-de]quinoxaline products. Steric
      bulk in both the dihydroimidazole and the dipolarophile allows isolation of an
      imidazo[1,2-a]indole, the initial product of cycloaddition. When the bromomethyl
      ketone contains no other functionality, or when cycloaddition is inhibited due to
      steric constraints, the dihydroimidazolium ion undergoes ring-opening hydrolysis
      followed by recyclization of the exposed amino ketone to afford either 3-alkyl-1
      formylpiperazine-2-ones or 3-aryl-1-formyl-1,4,5,6-tetrahydropyrazines.

PMID- 16886086
TI  - A cationic lanthanide complex binds selectively to phosphorylated tyrosine sites,
      aiding NMR analysis of the phosphorylated insulin receptor peptide fragment.
AB  - The binding of two cationic europium complexes to a differentially phosphorylated
      insulin receptor peptide has been studied by emission spectroscopy and (31)P NMR
      and (1)H NMR TOCSY methods. Analysis of the europium emission and NMR spectral
      data was consistent with the presence of species in slow exchange on the NMR and
      emission timescales, in agreement with selective binding of the lanthanide ion to
      the phospho-tyrosine site, allowing such complexes to be considered as
      prototypical chemoselective paramagnetic derivatising agents.

PMID- 16886087
TI  - Intracellular photodynamic therapy with photosensitizer-nanoparticle conjugates:
      cancer therapy using a 'Trojan horse'.
AB  - Phthalocyanine-nanoparticle conjugates have been designed and synthesised for the
      delivery of hydrophobic photosensitizers for photodynamic therapy (PDT) of
      cancer. The phthalocyanine photosensitizer stabilized gold nanoparticles have an
      average diameter of 2-4 nm. The synthetic strategy interdigitates a phase
      transfer reagent between phthalocyanine molecules on the particle surface that
      solubilises the hydrophobic photosensitizer in polar solvents enabling delivery
      of the nanoparticle conjugates to cells. The phthalocyanine is present in the
      monomeric form on the nanoparticle surface, absorbs radiation maximally at 695 nm
      and catalytically produces the cytotoxic species singlet oxygen with high
      efficiency. These properties suggest that the phthalocyanine-nanoparticle
      conjugates are ideally suited for PDT. In a process that can be considered as
      cancer therapy using a 'Trojan horse', when the nanoparticle conjugates are
      incubated with HeLa cells (a cervical cancer cell line), they are taken up thus
      delivering the phthalocyanine photosensitizer directly into the cell interior.
      Irradiation of the nanoparticle conjugates within the HeLa cells induced
      substantial cell mortality through the photodynamic production of singlet oxygen.
      The PDT efficiency of the nanoparticle conjugates, determined using colorimetric
      assay, was twice that obtained using the free phthalocyanine derivative.
      Following PDT with the nanoparticle conjugates, morphological changes to the HeLa
      cellular structure were indicative of cell mortality via apoptosis. Further
      evidence of apoptosis was provided through the bioluminescent assay detection of
      caspase 3/7. Our results suggest that gold nanoparticle conjugates are an
      excellent vehicle for the delivery of surface bound hydrophobic photosensitizers
      for efficacious photodynamic therapy of cultured tumour cells.

PMID- 16886088
TI  - Re-absorption of chlorophyll fluorescence in leaves revisited. A comparison of
      correction models.
AB  - The application of correction methods to account for re-absorption of chlorophyll
      fluorescence emission in leaves is subject to a number of controversies in the
      literature. These uncertainties lead to high discrepancies in the corrected
      spectral distribution of fluorescence and consequently in the interpretation of
      related physiological features of plants, according to the chosen method used in
      the process of correction. In this research, three correction methods, based on
      transmittance and/or reflectance measurements on leaves, were analysed
      comparatively. One method gave high values for the corrected fluorescence ratio
      between 685 nm and 737 nm (F685/F737 approximately 7 to 20 according to the
      different species of leaves). The two other methods were found to give similar
      results with corrected fluorescence ratios around a value of two (F685/F737
      approximately 2). While the first method was developed in the light of empirical
      considerations, the latter two models are based upon defined physical approaches
      depicting interaction between light and matter. The theoretical basis of these
      methods, the validation methodologies used to support them and the similarity in
      the spectra corrected by light re-absorption for both models, all showed that
      they should be treated as confident and suitable approximations to solve the
      problem of light re-absorption in leaves.

PMID- 16886089
TI  - Chlorin p6 as a fluorescent probe for the investigation of surfactant
      cyclodextrin interactions.
AB  - Cyclodextrins (CD) are often proposed as potential vehicles in targeted drug
      delivery. However, if the membrane structure is disrupted by CD, then it cannot
      be considered to be a good drug delivery vehicle. When an extrinsic fluorescence
      probe is used to monitor such interactions, there are no less than three possible
      equilibria that can operate simultaneously: surfactant-cyclodextrin, surfactant
      fluorophore and cyclodextrin-fluorophore. The fluorescence intensity/lifetime
      might be affected by all these and so, the results depend strongly on the
      fluorophore used as well as the nature of the surfactant. This aspect highlights
      the importance of the suitability of the fluorescence probe to be used to study
      complicated systems and interaction. In the present work, chlorin p6, prepared
      from chlorophyll from spinach leaves, has been used as the fluorescence probe to
      investigate the interaction between alpha-CD and beta-CD with the neutral
      surfactants Triton X 100 (TX 100) and cetyl trimethyl ammonium bromide (CTAB).
      The fluorophore is found to be a sensitive one for the study of the interaction
      of alpha, beta and gamma-CD with the surfactants TX 100 and CTAB. It is found
      that contrary to earlier reports, a complex between alpha-CD and TX 100 is
      formed, even though the binding constant is not very high. This observation can
      be obtained with chlorin p6, which does not bind to the CDs, but not with a
      fluorophore, which binds to the CD as well and thus complicates the situation as
      the binding with CD is stronger than that between TX 100 and alpha-CD as compared
      to that between TNS and CD.

PMID- 16886090
TI  - Modeling pigment contributions to spectral reflection of apple fruit.
AB  - A simple approach for spectral reconstruction of spectral reflection by whole
      apple fruit is described. It is shown that an approximation to the reflection
      spectrum can be obtained by making a simple assumption on the shape of the
      featureless scattering and using known spectral properties of the following
      pigment pools: (i) thylakoid-bound chlorophylls and carotenoids, (ii)
      cuticular/vacuolar phenolics, (iii) extrathylakoid chloroplasts/chromoplasts
      carotenoids, and (iv) vacuolar anthocyanins. The in vivo spectra of individual
      pigment pools estimated in bleaching experiments or as a difference between fruit
      with high and low pigment content are presented. In most cases simulations based
      on a linear combination of spectra proved to be effective, but fruit with high
      chlorophyll content necessitated the use of a non-linear model. The models
      succeeded in simulating reflection spectra of fruit widely differing in pigment
      content and composition with relative error lower than +/-4% over the visible
      range. The estimated relative contributions by the pigment pools into total
      reflection were found to be sensitive indicators of apple fruit ripening and
      could be useful in evaluating the light screening efficacy by flavonoids and
      carotenoids under stress conditions.

PMID- 16886091
TI  - The effect of folic acid on porphyrin synthesis in tumors and normal skin of mice
      treated with 5-aminolevulinic acid or methyl 5-aminolevulinate.
AB  - 5-Aminolevulinic acid (ALA) or its derivative methyl 5-aminolevulinate (MAL)
      combined with folic acid was applied in nude mice bearing human colon
      adenocarcinoma. The aim of the study is to see whether folic acid may increase
      biosynthesis of porphyrins in tumor tissue after systemic or topical
      administration of ALA or MAL. The production of porphyrins was determined by
      spectrofluorometric measurements with an optical fibre probe. It was found that
      the porphyrin production after i.p injection of 200 mg kg(-1) ALA or MAL was
      significantly increased by i.p injection of 100 mg kg(-1) folic acid. However, in
      the case of topically applied 20% ALA, folic acid had no effect. In the case of
      topically applied 20% MAL, folic acid (i.p or topically applied) reduced the
      porphyrin synthesis. This might be used for the protection of normal skin against
      photosensitization. The effects of folic acid were similar in tumors and normal
      skin. Two mechanisms may explain the results: enhancement of the efficiency of
      the rate-limiting enzyme porphobilinogen deaminase by folic acid or interference
      of folic acid with the transport of ALA and MAL to and into the cells
      synthesizing porphyrins in the tissues. The present data seem to favour the
      latter mechanism. Folic acid may have a role as an adjuvant in photodynamic
      therapy with systemically administered ALA and its derivatives.

PMID- 16886092
TI  - Effects of cadmium and enhanced UV radiation on the physiology and the
      concentration of UV-absorbing compounds of the aquatic liverwort Jungermannia
      exsertifolia subsp. cordifolia.
AB  - The aquatic liverwort Jungermannia exsertifolia subsp. cordifolia was cultivated
      for 15 d under controlled conditions to study the single and combined effects of
      cadmium and enhanced ultraviolet (UV) radiation. Both cadmium and UV radiation
      caused chlorophyll degradation and a decrease in the maximum quantum yield of
      photosystem II (PSII), together with an increase in the mechanisms of non
      photochemical dissipation of energy (increase in the xanthophyll index). Cadmium
      was more stressing than UV radiation, since the metal also influenced
      photosynthesis globally and caused a decrease in net photosynthetic rates, in the
      effective quantum yield of photosynthetic energy conversion of PSII, and in the
      maximal apparent electron transport rate through PSII. Ultraviolet radiation
      increased the level of trans-p-coumaroylmalic acid and cadmium increased trans
      phaselic and feruloylmalic acids. The increase in these compounds was probably
      related to both a more efficient absorption of harmful UV radiation and an
      enhanced protection against oxidative stress. DNA damage was specifically caused
      by UV-B radiation, but was intensified under the presence of cadmium, probably
      because the metal impairs the DNA enzymatic repair mechanisms. Ultraviolet
      radiation and cadmium seemed to operate additively on some physiological
      processes, while other responses were probably due to either factor alone.

PMID- 16886093
TI  - Redistribution of Foscan from plasma proteins to model membranes.
AB  - Photodynamic therapy is a comparatively novel modality of tumours treatment that
      includes simultaneous action of photosensitizers, light and oxygen.
      Photosensitizer redistribution between plasma proteins and biomembranes define
      photosensitizers interaction with cells, their intracellular localization and
      kinetics of sensitizers accumulation in the tumour. Present study investigates
      the kinetics of Foscan release from plasma proteins to model membranes using
      fluorescence resonance energy transfer (FRET) from label, covalently bound to
      protein, to sensitizer. We have demonstrated very slow kinetics of Foscan release
      from protein complexes with rate constants of (1.7 +/- 0.1) x 10(-3) s(-1) for
      albumin and (1.6 +/- 0.3) x 10(-4) s(-1) for high-density lipoproteins (HDL).
      Foscan redistributes by both collision and diffusion-mediated transfer from
      complexes with HDL, with bimolecular rate constant k(out) = (8.8 +/- 1.4) x 10(
      2) M(-1) s(-1). Thermodynamic considerations proposed that sensitizer release
      from HDL into the aqueous medium is unfavourable and collision mechanism appeared
      to be a preferred mode of transfer in biological environment. Slow rates of
      Foscan redistribution from plasma proteins should be considered while planning
      dosimetry protocol of Foscan-PDT.

PMID- 16886095
TI  - Underweight, weight loss and related risk factors among older adults in sheltered
      housing--a Swedish follow-up study.
AB  - BACKGROUND: Underweight and weight loss are important factors in detecting
      malnutrition. OBJECTIVE: To describe underweight, weight loss and related
      nutritional factors after 12 months among individuals 75 years or older and
      living in sheltered housing. A further aim was to identify possible risk factors
      associated with underweight and weight loss. DESIGN: This is a part of a cross
      sectional follow-up study from a county in Sweden, examining the disabilities,
      resources and needs of 719 older adults in sheltered housing units. Data were
      collected twice, with a 12-month interval using the Resident Assessment
      Instrument. RESULTS: Among the 503 remaining chronically ill individuals with
      cognitive and functional disabilities, 35% were classified as underweight at the
      initial assessment and 38% at the second, a non-significant difference. A further
      analysis showed 39% had decreased weight, 27% remained stable and 28% gained
      weight. A weight loss of 5% occurred in 27% of the older adults and a loss of 10%
      occurred in 14%. Risk factors associated with being underweight and weight loss,
      using scales derived from the instrument were cognitive and functional decline.
      Dementia and Parkinson's disease, eating dependencies and constipation were the
      strongest risk factors when analyzed as single items. CONCLUSION: A high
      percentage was underweight or exhibited weight loss and several risk factors were
      identified. Ensuring adequate nutritional status in individuals with a variety of
      diseases and declining health status is challenging. Increased combined efforts
      using a wide range of measures, nutritional programs and routines need to be
      regularly implemented.

PMID- 16886094
TI  - Trace copper levels in the drinking water, but not zinc or aluminum influence CNS
      Alzheimer-like pathology.
AB  - Mounting evidence suggests copper may influence the progression of Alzheimer's
      disease by reducing clearance of the amyloid beta protein (Abeta) from the brain.
      Previous experiments show that addition of only 0.12 PPM copper (one-tenth the
      Environmental Protection Agency Human consumption limits) to distilled water was
      sufficient to precipitate the accumulation of Abeta in the brains of cholesterol
      fed rabbits (1). Here we report that addition of copper to the drinking water of
      spontaneously hypercholesterolemic Watanabe rabbits, cholesterol-fed beagles and
      rabbits, PS1/APP transgenic mice produced significantly enhanced brain levels of
      Abeta. In contrast to the effects of copper, we found that aluminum- or zinc-ion
      supplemented distilled water did not have a significant effect on brain Ab
      accumulation in cholesterol-fed rabbits. We also report that administration of
      distilled water produced a reduction in the expected accumulation of Ab in three
      separate animal models. Collectively, these data suggest that water quality may
      have a significant influence on disease progression and Ab neuropathology in AD.

PMID- 16886096
TI  - Resting metabolic rate in elderly nursing home patients with multiple diagnoses.
AB  - BACKGROUND: In the diseased elderly weight loss and malnutrition are common. It
      is unclear to what degree this is caused by an elevated resting metabolic rate
      (RMR), a decreased energy intake or a combination of the two. OBJECTIVE: To
      measure RMR and nutrient induced thermogenesis (NIT) in chronically diseased
      elderly living in a nursing home and test for a correlation with fat free mass
      (FFM), age, energy intake and activities of daily living (ADL). DESIGN:
      Explorative study performed in the residents' own apartments. RMR was measured by
      indirect calorimetry, and NIT was tested by giving the subjects an oral fluid
      test meal, then measuring metabolic rate again one hour later. Body composition
      was measured anthropometrically and FFM was calculated. Energy intake was
      calculated from a five-day record of weighed food. BMR was calculated using four
      different prediction equations and compared with measured RMR. RESULTS: RMR was
      1,174 kcal/d (29.3 kcal/kg FFM/d). The variation in RMR was significantly related
      to FFM (p < 0.0001). Energy intake was 1,474 kcal/d, (36.5 kcal/kg FFM/d). The
      energy intake/RMR ratio, was 1.27, and NIT was 15% (0-33%). NIT was not
      correlated to any of the parameters tested. The equation of Harris and Benedict
      underestimated BMR by 4%; the WHO/FAO overestimated BMR by 7%; Schofield and an
      estimate of 20 kcal/kg/d did not significantly differ from the measured mean.
      CONCLUSION: RMR was closely correlated to FFM. Variations in NIT could not be
      explained by any tested parameters. Predicted BMR differed from measured RMR by
      less than 8% in all methods, but individual variations were large.

PMID- 16886097
TI  - Protein turnover and requirements in the healthy and frail elderly.
AB  - There are as yet no definitive data that warrant the establishment of evidence
      based dietary protein recommendations for the elderly. We reviewed the relevance
      of the new 2002 recommended protein intake of 0.80 g/kg body weight.d for adults
      to healthy and frail elderly persons. We found that data from published nitrogen
      balance studies indicate that, a higher protein intake of 1.0 - 1.3 g/k.d is
      required to maintain nitrogen balance in the healthy elderly, which may be
      explained by their lower energy intake and impaired insulin action during feeding
      compared with young persons. Although it needs to be confirmed, a decrease in
      efficiency of protein utilization with aging may also dictate a higher protein
      intake recommendation. Measures of the dynamic aspects of protein metabolism done
      in the postabsorptive state have shown no change in whole body protein turnover
      per unit of active metabolic tissue with aging. However, the contribution of
      muscle protein to wholebody protein metabolism was significantly reduced in the
      elderly, and explained by their reduced muscle mass and lower rates of
      myofibrillar protein turnover. Consequently, the contribution of nonmuscle
      protein, especially that of visceral tissue whose rates of protein turnover are
      known to be more rapid was proportionally greater with aging. It is conceivable
      that higher protein consumption rates could compensate for the decrease in
      availability of muscle amino acids and spare the muscle mass. Despite a paucity
      of data on the frail elderly population, we present a rationale to justify a
      greater protein intake of at least equivalent to that of their healthy
      counterparts. We propose that higher protein intakes for the elderly, and
      especially the frail population, than those presently recommended may minimize
      the sarcopenia of aging and thereby protect against some of the health risks of
      aging.

PMID- 16886098
TI  - Diabetes mellitus, dementia, and cognitive function in older persons.
AB  - Dementia and cognitive decline are among the most common and most feared
      conditions of old age making the identification of modifiable risk factors for
      dementia an urgent public health priority. Recently, an increasing body of data
      suggests that type 2 diabetes mellitus, a common condition in older persons, is
      associated with the development of dementia and cognitive decline. A systematic
      review of the medical literature of the past 15 years identified 40 original
      report articles in the English language pertaining to the relation of diabetes to
      dementia and cognitive function in older persons. Most, but not all, of these
      studies suggest a detrimental effect of diabetes on cognitive function. Current
      research efforts are aimed at understanding the underlying neurobiologic
      mechanisms whereby diabetes causes dementia and cognitive impairment in order to
      develop rational interventions to prevent this recently documented adverse
      consequence.

PMID- 16886099
TI  - Glycosylated hemoglobin level and development of mild cognitive impairment or
      dementia in older women.
AB  - BACKGROUND: Biological mechanisms linking diabetes and cognition continue to
      grow, yet the association remains controversial in elders. Whether glycosylated
      hemoglobin (HbA1C) level, a marker of glucose control, is predictive of the
      development of cognitive impairment or dementia is unknown. We determined the
      association between HbA1C level and risk of developing cognitive impairment in
      older women, mostly without diabetes. METHODS: We studied 1983 postmenopausal
      women (mean age, 67.2 years) with osteoporosis who had HbA1C level measured at
      baseline. Development of mild cognitive impairment (MCI) or dementia over 4 years
      was determined as part of a dementia ancillary study. We analyzed risk of MCI or
      dementia for every 1% of HbA1C as well as risk associated with HbA1C >or= 7%.
      RESULTS: The mean level of HbA1C was 5.8% (range 3.0% to 12.1%) and 86 (4.3%)
      women developed MCI or dementia. For every 1% increase in HbA1C, women had a
      greater age-adjusted likelihood of developing MCI (OR= 1.50; 95% CI 1.14-1.97)
      and of developing MCI or dementia (OR=1.40; 95% CI 1.08 - 1.83). For those with
      HbA1C level >or= 7% (n=49), the age-adjusted risk for developing MCI was
      increased nearly 4-fold (OR= 3.70; 95% CI 1.51-9.09) and was increased nearly 3
      fold for developing MCI or dementia (OR=2.86; 95% CI 1.17-6.98). When we excluded
      women with diagnosed diabetes (n=53), the association between HbA1C and MCI
      lessened somewhat but remained elevated (unadjusted OR=1.59; 95% CI 1.01-2.50;
      age-adjusted OR=1.42; 95% CI 0.89-2.28). Multivariate analyses adjusted for age,
      education, race, depression, alcohol use and treatment with raloxifene yielded
      similar results. INTERPRETATION: We found an association between HbA1C level and
      risk of developing MCI or dementia in postmenopausal osteoporotic women primarily
      without diabetes. Our findings support the hypothesis that glucose dysregulation
      is a predictor for cognitive impairment.

PMID- 16886101
TI  - [Early diagnosis and rapid treatments of gastrointestinal fistula].
AB  - Traditional treatments of gastrointestinal fistula include early drainage,
      maintaining nutrition and then resection of fistula at the proper time,which
      usually take three to four months or even longer. Rapid treatments of
      gastrointestinal fistula mean promoting rapid spontaneous closure of tract
      fistula and early primary resection of fistula within two weeks after fistula
      occurrence. Early diagnosis is the premise of early management, and fistulography
      and abdominal CT scan are important early diagnostic methods. Most of fistula
      could close spontaneously in the maintaining stage. To promote the rapid closure,
      however, special measures including sufficient drainage, somatostatin and total
      parenteral nutrition in the early stage should be implemented to avoid intra
      abdominal collection of intestinal fluid and infection, control further leakage
      of intestinal fluid and improve nutritional status. In the late stage,when
      leakage of intestinal fluid could be controlled, recombine human growth hormone
      (rhGH) and enteral nutrition should be administered in place of somatostatin and
      total parenteral nutrition respectively. The fistula can reach rapid spontaneous
      closure in both stages. Fibrin glue and rhGH used at the same time can improve
      the curative rate and shorten the treatment time even more. In the 1960s and
      1970s, early primary resection of the fistula and re-anastomosis often resulted
      in anastomosis failure. The reasons for this included poor nutritional status,
      uncontrolled secretion of intestinal fluid, severe intra-abdominal infection and
      multiorgan dysfunction syndrome. Such stage management policy has been proposed,
      developed and persisted since late 1960s. Nowadays, the advance of medical
      science provided the possibility to change or improve the current policy. Our
      research proved that early resection of the primary fistula and re-anastomosis of
      the small bowel could be performed successfully in some selected patients whose
      general conditions are good and intestinal adhesion were not severe within ten to
      fourteen days after fistula occurrence. More studies are still needed to define
      the indications and contradictions for early resection of the primary
      gastrointestinal fistula, and prove the feasibility and rationality of rapid
      treatments of gastrointestinal fistula.

PMID- 16886102
TI  - [Surgery therapy of Crohn disease complicated with fistula].
AB  - OBJECTIVE: To investigate the surgical treatment of Crohn disease(CD) complicated
      with perforation or fistula. METHODS: The clinical data of 24 CD cases
      complicated with perforation or fistula treated in our department from Jan. 1980
      to Apr. 2005 were analyzed retrospectively. RESULTS: There were 24 cases of CD
      complicated with perforation or fistula among 181 CD patients,and the incidence
      of perforation or fistula was 13.3%. Steroid treatment before perforation was
      given in 8 patients, while not in 9 patients and unclear in 7 patients. Eighteen
      patients had single perforation, 4 patients two free perforations and 2 patients
      more than three extra-abdominal fistula. Emergency operation was performed in 8
      cases and selective operation in 16 cases. Five cases had postoperative
      complications including incision infection in 2, intra-abdominal abscess in 2 and
      stomal fistula in one case, and were all cured by surgical drainage and anti
      infection treatment. The morbidity rate was 20.8%. The postoperative mortality
      rate was 12.5% (3/24). Eighteen patients were followed up from 6 months to 18
      years, and the 5-year recurrent rate was 16.7%. The 10-year reoperation rate was
      33.3%. CONCLUSIONS: Steroid use is not the main cause of perforation or fistula
      in CD. Perforation or fistula is the definite indication for surgical treatment.

PMID- 16886100
TI  - Glycemia and cognitive function in older adults using glucose-lowering drugs.
AB  - OBJECTIVES: In experimental studies, both high and low levels of plasma glucose
      are associated with cognitive impairment. In populations, less is known about the
      relationship between glycemia and cognitive function, especially in persons using
      glucose-lowering drugs. DESIGN: A cross-sectional study of 378 high-functioning
      black and white men and women aged 70 to 79 participating in the Health, Aging,
      and Body Composition Study (Health ABC) who used glucose-lowering medications.
      Glycemic measures included fasting plasma glucose (FPG) and glycosylated
      hemoglobin (HbA1c). Cognitive function was assessed using the Modified Mini
      Mental State Examination (3MS) and the Digit Symbol Substitution Test (DSS) at
      the same examination visit in which the glycemic measures were determined.
      SETTING: Memphis, Tennessee and Pittsburgh, Pennsylvania. RESULTS: We observed an
      "inverted-U" relationship (p =.0025 for 3MS, p=.0277 for DSS) between FPG (range
      47 - 366 mg/dl) and performance on these two tests. The fasting plasma glucose
      levels associated with the highest score on the 3MS was 180 mg/dl and 135 mg/dl
      for the DSS. There was a monotonic inverse relationship between HbA1c and
      performance on 3MS and DSS without evidence of a threshold effect. CONCLUSION:
      Our findings suggest that older adults who are treated for diabetes may
      experience a small degree of cognitive impairment within the recommended fasting
      glucose levels, yet measures of long-term glycemic control support tight glycemic
      control. Given the high prevalence of diabetes and the common use of glucose
      lowering drugs in older adults, further studies are needed to elucidate these
      relationships.

PMID- 16886103
TI  - [Management of tertiary peritonitis in the patients complicated with intestinal
      fistula].
AB  - OBJECTIVE: To investigate the etiology and management of tertiary peritonitis in
      the patients with intestinal fistula. METHODS: One hundred and fifty-three cases
      of intestinal fistula complicated with tertiary peritonitis were reviewed. The
      microbiological characteristics, treatment Methods and outcomes were analyzed.
      RESULTS: There were 114 males and 39 females with a mean age of (42+/- 19) years.
      The main causes of intestinal fistula included gastrointestinal surgery (40.5%),
      trauma (31.4%) and severe pancreatitis (14.4%), etc. The most common cultured
      bacteria of 157 specimens from 79 patients with tertiary peritonitis were
      Escherichia coli (24.2%), Pseudomonas aeruginosa (12.1%), Staphylococcus aureus
      (10.8%), Enterobacter cloacae (10.2%), Klebsiella pneumoniae (8.3%). Debridement
      of the necrotic tissues, drainage of the abscess, continuous rinsing plus
      negative pressure drainage and antibiotics treatment were performed in 52 cases.
      Nineteen patients only changed from simple tube drainage to continuous rinsing
      plus negative pressure drainage. Twenty- eight patients changed to continuous
      rinsing plus negative pressure drainage and received antibiotics as well. Thirty-
      six patients received antibiotics and ecoimmune nutrition, while 18 patients only
      received ecoimmun nutrition. CONCLUSIONS: Intestinal fistula complicated with
      tertiary peritonitis was mainly caused by residual infectious focus and
      inappropriate drainage. The rational treatments include reoperation for
      debridement of the necrotic and infectious tissues, changing drainage to
      continuous rinsing plus negative pressure drainage, appropriate usage of
      antibiotics, and ecoimmune nutrition.

PMID- 16886105
TI  - [Characteristics of metastasis and recurrence following curative resection for
      colonic carcinoma].
AB  - OBJECTIVE: To investigate the characteristics of metastasis and recurrence
      following curative resection for colonic carcinoma,and analyze the prognosis.
      METHODS: The clinicopathological and follow-up data of 310 patients with colon
      carcinoma undergoing curative resection were analyzed retrospectively. RESULTS:
      The recurrence rate after curative resection was 23.2% (72/310). The 5-year
      survival rate was 64.6%. Hepatic metastasis accounted for 38.9% of the cases.
      Gross classification,histological type, differentiation, lymph node metastasis
      were correlated with metastasis/recurrence. Univariate analysis revealed that
      gross classification, histological type, differentiation, lymph node metastasis,
      blood vessel invasion, TNM Stage, postoperative chemotherapy, portal chemotherapy
      were prognostic factors. Cox regression analysis revealed that only gross
      classification, lymph node metastasis, postoperative chemotherapy, portal
      chemotherapy were independent prognostic factors. CONCLUSIONS: Liver is the most
      common metastatic site after curative resection for colonic carcinoma. Gross
      classification, lymph node metastasis, postoperative chemotherapy, and portal
      chemotherapy are independent prognostic factors.

PMID- 16886104
TI  - [Related factors and prognosis of hepatic metastasis and peritoneal dissemination
      in gastric cancer].
AB  - OBJECTIVE: To investigate the related factors and prognosis of peritoneal
      dissemination and hepatic metastasis in gastric cancer, and the impact of
      palliative surgery on the prognosis. METHODS: The clinicopathologic and follow-up
      data of the patients with gastric carcinoma treated in our hospital from Aug.
      1994 to Jul. 2005 were analyzed retrospectively. RESULTS: The clinicopathologic
      factors correlated with peritoneal dissemination included serosal penetration,
      whole stomach cancer, undifferentiated type, female and hepatic metastasis, while
      those correlated with hepatic metastasis included Borrmann IV, lymph node
      metastasis and peritoneal dissemination (P< 0.05). The postoperative one-year
      survival rate of the patients with hepatic metastasis (H group) were lower than
      that of the patients with peritoneal dissemination (P group)(P< 0.05). The one-
      year survival rate of the patients with peritoneal dissemination undergoing
      palliative resection was significantly higher than that of the patients
      undergoing by-pass operation or feeding neostomy, and exploratory laparotomy (P<
      0.05), while there was no significant difference among the three groups of the
      patients with hepatic metastasis. CONCLUSIONS: The short-term prognosis of the
      patients with hepatic metastasis is poorer than that of the patients with
      peritoneal dissemination. Palliative resection could improve the short-term
      survival rate of the patients with peritoneal dissemination, while it had no
      significant impact on the survival rate of the patients with hepatic metastasis.

PMID- 16886106
TI  - [Comparative study on long-term results of laparoscopic and open radical
      resection for colorectal carcinoma].
AB  - OBJECTIVE: To compare the long-term results of laparoscopic and open radical
      resection for colorectal carcinoma. METHODS: Two hundred and fifteen patients
      with colorectal cancer from January 1996 to September 2000 were non-randomly
      divided into laparoscopic and open operation groups. Local recurrence, distant
      metastasis, 5-year survival rate and long-term postoperative complications were
      compared between the two groups. RESULTS: Eighty-seven cases received
      laparoscopic resection and 128 cases received open operation. There were no
      statistical differences in age, sex and tumor stage between the two groups (P >
      0.05). The 5-year-survival rate was 70% in open operation group, and 78% in
      laparoscopic group (P > 0.05). There were no significant differences in the
      incidences of local recurrence, distant metastasis, incision seeding, and
      incision hernia between the two groups (P > 0.05). The complication rate of
      postoperative adhesive intestinal obstruction was significantly lower in
      laparoscopic group than that in open operation group (P< 0.05). CONCLUSIONS: Long
      term results of laparoscopic resection are similar to those of open resection for
      colorectal carcinoma, but laparoscopic surgery has less long-term complications.

PMID- 16886107
TI  - [Comparison of inflammatory response after laparoscopic and conventional surgery
      for colorectal carcinoma].
AB  - OBJECTIVE: To compare the systemic and local inflammatory response after
      laparoscopic and conventional surgery for colorectal carcinoma. METHODS: From
      April 2004 to August 2004, 51 colorectal cancer patients undergoing laparoscopic
      (n=25) and conventional open (n=26) colorectal resection were enrolled in the
      study. The general clinical data,and inflammatory response were compared between
      the two groups. RESULTS: There were no significant differences in age, sex, pre
      operative levels of haemoglobin and albumin, Dukes stage and surgical procedure
      between the two groups (P > 0.05). Laparoscopic surgery had more advantages over
      conventional open surgery such as incision, operating time, recovery time of
      bowel function, and hospitalization. On postoperative day (POD) 1, WBC count
      [(7.30+/- 2.62)x10(9)/L], and the serum levels of IL-10 [(19.46+/- 3.31)pg/ml]
      and C-reactive protein (CRP) [(2.76+/- 2.17)mg/dl] were significantly lower in
      laparoscopic group than those in conventional group (P< 0.05), but there were no
      differences on POD 4 between the two groups (P > 0.05). There were no significant
      differences in the volume of peritoneal drainage fluid, and levels of IL-10, TNF
      and CRP in it on POD 1 between the two groups, but the volume of peritoneal
      drainage fluid decreased significantly from POD 2, and the level of IL-10 in it
      was significantly lower on POD 4 in laparoscopic group than that in conventional
      group. CONCLUSIONS: In early stage after operation,intra- peritoneal inflammatory
      response caused by laparoscopic surgery is similar to that by conventional open
      surgery, but systemic inflammatory response is slighter than that by conventional
      open surgery for colorectal carcinoma.

PMID- 16886108
TI  - [Comparative study on three types of digestive reconstruction after total
      gastrectomy].
AB  - OBJECTIVE: To investigate the rational digestive reconstruction after total
      gastrectomy for gastric malignancy. METHODS: Three types of digestive
      reconstruction were performed after total gastrectomy in 189 cases with gastric
      carcinoma. The operating time, morbidity and mortality, food intake, digestive
      tract symptoms, nutritional status at 1 and 3 years after surgery and 1-, 3-, 5
      year cumulative survival were compared. RESULTS: There were no significant
      differences among the three procedures in operative morbidity and mortality,
      postoperative food intake, nutritional status (Hemoglobin, total protein and
      labium), and incidences of diarrhea and dumping syndrome (P > 0.05). The overall
      1-, 3-, 5-year survival rates were 75.3%, 38.2% and 20.5% respectively, and there
      were no significant differences among the three groups (P > 0.05). Orr-type and P
      type esophagojejunostomy had an advantage of anti-esophageal reflux, and were
      obviously superior to Moynihan-type anastomosis (P< 0.01). Compared with P-type
      reconstruction, Orr-type reconstruction was simpler with shorter operating time,
      and less complications. CONCLUSIONS: Orr-type Roux-en-Y esophagojejunostomy can
      be recommended as an adaptable method of digestive reconstruction after total
      gastrectomy for gastric cancer because of its avoiding reflux esophagitis,
      maintaining better nutritional status and quality of life, and simpler procedure.

PMID- 16886109
TI  - [Clinical analysis of gastroparesis syndrome after nongastrectomy abdominal
      operation: a report of 22 cases].
AB  - OBJECTIVE: To investigate the causes, diagnosis and treatment of gastroparesis
      syndrome after nongastrectomy abdominal operation. METHODS: The clinical data of
      22 cases with gastroparesis syndrome after nongastrectomy abdominal operation
      from 1972 to 2004 were retrospectively analyzed. RESULTS: Gastroparesis syndrome
      after nongastrectomy abdominal operation often occurred during 4-6 days
      postoperatively when the patients began to take in food, characterized by upper
      abdominal distension, nausea, vomiting, strong splashing bowel sound, weak bowel
      sound and large quantity of gastric drainage ranging from 1000 to 3000 ml every
      day. Barium meal was valuable not only in the diagnosis but also effective for
      promoting gas motility. It revealed a non-peristaltic, flabby and static stomach,
      and retention of contrast medium in the stomach even 5-6 hours later. All the
      patients recovered through non-operative therapy for 5-25 days including
      continuous gastrointestinal decompression, TPN and gastro-intestinal dynamic
      medicine. CONCLUSIONS: The causes of gastroparesis syndrome after nongastrectomy
      abdominal operation are multifactorial, most of such patients can be cured by non
      operative therapy.

PMID- 16886110
TI  - [Clinical use of endoscopic ileus tube drainage in preoperative therapy for acute
      low malignant colorectal obstruction].
AB  - OBJECTIVE: To evaluate the clinical use of endoscopic ileus tube drainage in
      preoperative therapy for acute low malignant colorectal obstruction. METHODS:
      From Nov. 2004 to Dec. 2005, 15 cases with acute low malignant colorectal
      obstruction received emergency colonoscopy and endoscopic ileus tube drainage was
      performed. Radical resection was then performed after seven days of drainage.
      RESULTS: Endoscopic ileus tube drainage was successful in 13 cases, and failed in
      2 cases because the guide wire cannot be inserted through the tumor in one case,
      and in the other case the tumor was located in the middle of the transverse colon
      so that the ileus drainage tube was not long enough. Abdominal girth decreased
      from (91+/- 4) cm to (82+/- 2) cm after tube drainage. The everyday drainage
      volume minus rinsing volume ranged from - 600 ml to 3200 ml. Abdominal X ray
      showed that obstruction was relieved. Intra-operative exploration revealed that
      colon edema was not evident, which increased resection rate. CONCLUSION:
      Endoscopic ileus tube drainage is effective, safe and maybe the first choice of
      acute low malignant colorectal obstruction.

PMID- 16886111
TI  - [Clinical trial of rectocele repair with longitudinal incision and transverse
      suture on the vaginal posterior wall].
AB  - OBJECTIVE: To investigate the clinical efficacy of rectocele repair with
      longitudinal incision and transverse suture on the vaginal posterior wall.
      METHODS: One hundred and forty-six patients with rectocele were enrolled in our
      study from August 1999 to August 2003. The patients were randomly divided into
      two groups, and received traditional repair with longitudinal incision and
      longitudinal suture (control group, n=74) or repair with longitudinal incision
      and transverse suture on the vaginal posterior wall (study group, n=72). The
      efficacy and complications were compared between the two groups. RESULTS: In the
      study group,only one case (1.4%) had no effect, and the total effective rate was
      98.7%. The mean course of treatment was (11.0+/- 1.9) days. Only two cases (2.7%)
      had postoperative complication. In the control group, 8 cases (11.1%) had no
      effect, and the total effective rate was 88.9%. The mean course of treatment was
      (17.4+/- 1.6) days. Twenty-nine cases (40.3%) had postoperative complications.
      There were significant differences in the efficacy and complications between the
      two groups (both P< 0.01). CONCLUSION: The refined rectocele repair with
      longitudinal incision and transverse suture on the vaginal posterior wall has
      good efficacy with shorter curative period and less complications.

PMID- 16886112
TI  - [Adult intestinal heterotopic gastric mucosa resulting in alimentary tract
      hemorrhage: a report of 11 cases].
AB  - OBJECTIVE: To investigate the clinical characteristics,diagnosis and treatment of
      intestinal heterotopic gastric mucosa resulting in alimentary tract hemorrhage.
      METHODS: Eleven cases of intestinal heterotopic gastric mucosa with alimentary
      tract hemorrhage during the past 24 years in our hospital were reviewed and the
      clinical data were analyzed retrospectively. RESULTS: The median age was 29 years
      old. Nine cases had abdominal pain, and radionuclide (99m)Tc-pertechnetate scan
      revealed bleeding lesion in 6 cases preoperatively. Segmental resection of the
      intestine with bleeding lesion were performed in all patients, postoperative
      pathology confirmed heterotopic gastric mucosa. The lesion was located in the
      jejunum in five cases and in the ileum in six cases. All lesions were complicated
      with diverticulum, or inflammatory mass on the intestinal wall, or abnormity of
      intestinal duplication. CONCLUSIONS: Intestinal heterotopic gastric mucosa is
      difficult to be diagnosed preoperatively, and radionuclide (99m)Tc-pertechnetate
      scan plays a role in preoperative diagnosis.

PMID- 16886113
TI  - [Comparative study on clinical effect of postoperative arterial infusion
      chemotherapy and systemic chemotherapy in gastric cancer].
AB  - OBJECTIVE: To compare the clinical effect of postoperative arterial infusion
      chemotherapy and systemic chemotherapy in gastric cancer. METHODS: From July 1997
      to July 2002, the patients undergoing radical gastric resection were randomly
      divided into two groups, and received systemic or arterial infusion chemotherapy
      three weeks after radical resection. Systemic chemotherapy was carried out for
      two courses with 5-fluorouracil (5-FU), pirarubicin (THP), and mitomycin (MMC)
      administered according to FAM program, while arterial infusion chemotherapy for
      four courses with the same anticancer drugs infused via the celiac artery. The
      outcomes were compared. RESULTS: Systemic chemotherapy was carried out in 188
      cases, and arterial infusion chemotherapy in 180 cases. There were no significant
      differences in sex, age, tumor location, histological type, TNM stage and
      surgical procedure between the two groups (P > 0.05). The 1, 3, 5 year survival
      rates were 87.2%, 53.7% and 43.1% in systemic chemotherapy, and 93.3%, 72.2% and
      53.6% in arterial infusion chemotherapy respectively (P< 0.01). CONCLUSION: The
      survival rate of the patients with arterial infusion chemotherapy is higher than
      that with systemic chemotherapy, which indicates that arterial infusion
      chemotherapy can remarkably improve the prognosis of the patients with gastric
      cancer.

PMID- 16886114
TI  - [Comparative study of postoperative early enteral nutrition and parenteral
      nutrition in esophageal carcinoma].
AB  - OBJECTIVE: To investigate the effect of postoperative early enteral nutrition
      (EN) and parenteral nutrition (PN) on nutritional status and morbidity in
      esophageal carcinoma. METHODS: One hundred and six patients with esophageal
      carcinoma were randomly divided into two groups, and received enteral
      nutrition(n=53) or parenteral nutrition(n=53) continuously for 7 days after
      operation. The body weight, blood routine test, liver function, and morbidity on
      postoperative day 8 were compared with those before operation. RESULTS: The body
      weight, red blood cell count, and the levels of hemoglobin, serum albumin and
      transaminase decreased less in EN group than those in PN group(P< 0.01). The
      complication rates of anastomotic fistula, pulmonary infection, pleural effusion
      and delayed incision healing were 0, 5.7%, 3.8% and 0 in EN group, and 5.7%,
      28.3%, 15.1% and 7.6% in PN group. There were significant differences between the
      two groups(P< 0.05). CONCLUSION: Early postoperative enteral nutrition after
      esophageal carcinoma surgery can improve nutritional status and reduce
      complications in comparison with parenteral nutrition.

PMID- 16886115
TI  - [Establishment of liver metastasis model of human primary colonic lymphoma by
      orthotopic transplantation].
AB  - OBJECTIVE: To provide an ideal animal model for exploring pathogenesis and
      experimental treatment of primary colonic lymphoma. METHODS: Primary colonic and
      liver metastatic lymphoma tissues were obtained from the surgical specimens,and
      transplanted into colonic mucosa of nude mice respectively. The tumorigenesis,
      invasion, metastasis and morphology of the transplanted tumor were observed.
      Karyotype was analyzed and DNA content was measured. RESULTS: According to the
      new WHO classification of malignant lymphoma, two high metastatic models (HCBL
      0303 from primary lymphoma and HCBL-0304 from live metastatic lesion) of human
      primary colonic non-Hodgkin's B cell lymphoma in nude mice were established
      successfully by orthotopic transplantation. Pathological examination showed
      poorly differentiated non-Hodgkin's B cell lymphoma of the transplanted tumors,
      and immunohistochemical staining showed positive expressions of CD19, CD20 and
      CD22, and negative expressions of CD3 and CD7. The number of chromosome ranged
      from 55 to 59, and DNA index (DI) was 1.59 - 1.71 (i.e. heteroploid). In HCBL
      0303,liver metastasis rate was 63.7% and lymph node metastasis rate was 56.4%.
      However, in HCBL-0304, both metastasis rates of liver and lymph node were 100%.
      The transplanted tumors grew autonomously and invasively in nude mice, and
      further developed hematogenous, lymphatic metastasis and intraperitoneal seeding.
      CONCLUSIONS: HCBL-0303 and HCBL-0304 are the first established high metastatic
      models of primary colonic lymphoma, and can be applied to the research on
      pathogenesis, invasion,metastasis and experimental therapy of human primary
      colonic lymphoma.

PMID- 16886116
TI  - [Serotonin transporter gene polymorphism in slow transit constipation].
AB  - OBJECTIVE: To investigate the association between the polymorphism of serotonin
      transporter gene-linked polymorphic region(5-HTTLPR) and slow transit
      constipation(STC). METHODS: Polymerase chain reaction was used to assess 5-HTTLPR
      polymorphism of SERT gene in 54 patients with STC and 100 healthy controls.
      RESULTS: The frequencies of serotonin transporter short/short(S/S) and allele S
      genotypes were significantly higher in STC patients than those in controls(72.2%
      vs 50.0%; 83.3% vs 72.5%; both P< 0.05). There were no significant differences in
      5-HTTLPR polymorphism respectively between the two groups according to gender and
      age(less than 45 and more than 45 years old). The frequency of S/S genotype was
      higher in the patients with less than 40% of the ingested markers evacuated
      within 72 h than those with more than 40% evacuated(71.7% vs 42.6%, P< 0.05).
      CONCLUSION: The presence of 5-HTTLPR allele S may contribute to the pathogenesis
      of STC.

PMID- 16886117
TI  - [Target lethal effect of recombinant soluble Fas coupled with protein kinase C
      inhibitor on colorectal carcinoma cells].
AB  - OBJECTIVE: To study the target killing effect of soluble Fas(sFas) coupled with
      protein kinase C(PKC) inhibitor on colorectal carcinoma cells. METHODS: The
      extracellular region of Fas protein was cloned and amplified by RT-PCR, and the
      expressing vector pGEX-4T-1-sFas was constructed. The sFas protein was purified
      by GST fusion protein purification system and coupled with Calphostin C(one kind
      of PKC inhibitor). The killing effect of soluble Fas coupled with PKC inhibitor
      on FasL-positive colorectal carcinoma cells was detected. RESULTS: After
      amplifying and cloning, the extracellular region of Fas protein, a 571 bp
      fragment, was proved by limited enzyme cutting and DNA sequencing. The expressed
      and purified protein was identified by Western Blot after transformed into E.
      coli BL21. The coupled sFas-Calphostin C showed suppressant activity on PKC
      kinase by the PKC kinase activity assay kit. The growth suppression rate of FasL
      positive colorectal carcinoma HR-8348 cells treated with sFas-Calphostin C was
      significantly higher than that of FasL-negative cells, but the killing effect of
      sFas-Calphostin C on normal human monocyte was not obvious. Compared with 5-Fu
      alone, the growth suppression rate of FasL-positive colorectal carcinoma HR-8348
      cells was significantly raised by sFas-Calphostin C combined with 5-Fu.
      CONCLUSION: The recombinant of soluble Fas and PKC inhibitor shows target killing
      effect on colorectal carcinoma cells.

PMID- 16886118
TI  - [Effect of angiogenesis inhibitor SU6668 on the growth and metastasis of gastric
      cancer in SCID mice].
AB  - OBJECTIVE: To study the effect of angiogenesis inhibitor SU6668 on the growth and
      metastasis of gastric cancer in SCID mice. METHODS: Metastatic model was
      established by orthotopic implantation of histologically intact human tumor
      tissue into the gastric wall of SCID mice. Forty-eight mice were randomly divided
      into four groups, and saline, 5-FU, SU6668, and 5-FU plus SU6668 were
      administered by i.p. every day for 6 weeks after tumor implantation. The mice
      were killed and tumor weight, tumor inhibition rate, intratumoral microvessel
      density(MVD), apoptotic index(AI) and metastasis inhibition were evaluated.
      RESULTS: Compared with the control, tumor growth was significantly inhibited in
      mice treated respectively with 5-FU, SU6668 and 5-FU plus SU6668 with inhibition
      rates of 47.5%, 64.1% and 69.2% respectively. Decreased MVD and increased AI were
      noted in the mice treated with SU6668 and 5-FU plus SU6668. The incidences of
      liver and peritoneal metastases was significantly inhibited and decreased to
      62.5%, 69.9% in SU6668 group, and 74.9%, 90% in 5-FU plus SU6668 group. The
      growth and metastasis of human gastric cancer implanted in SCID mice were
      significantly inhibited in SU6668 group and combined group, especially in
      combined group. CONCLUSION: Angiogenesis inhibitor SU6668 has a strong inhibitory
      effect on tumor growth and metastasis of human gastric cancer transplanted in
      SCID mice, and has synergistic effect combined with cytotoxic agents.

PMID- 16886119
TI  - [Expression of P33ING1, P53 and their relationship with apoptosis in anal canal
      carcinoma].
AB  - OBJECTIVE: To explore the expressions of P33ING1, P53 and their relationships
      with apoptosis in anal canal carcinoma (ACC). METHODS: The expressions of
      P33ING1, P53 proteins were measured by immunohistochemistry method (SP method),
      and apoptosis was detected in 42 cases with ACC, 36 cases with anal canal adenoma
      (ACA) or anal canal papilloma (ACP), and 40 cases with paraanal inflammatory
      mass(PAIM). RESULTS: The positive expression rates of P33ING1 and P53 proteins
      were 40.5% (17/42), 97.2% (35/36) and 97.5% (39/40), 50.0% (21/42), 22.2% (8/36)
      and 27.5% (11/40) respectively, and the average apoptosis indexes(AI) were
      (10.27+/- 1.23) per thousand, (42.75+/- 0.98) per thousand and (42.67+/- 1.04)
      per thousand respectively in ACC, ACA or ACP and PAIM. There were significant
      differences in the positive expression rates of P33ING1, P53 and apoptosis index
      between ACC and the other two groups respectively (P< 0.05). Among 21 cases of
      ACC with positive expression of P53 protein,there were 18 cases with P33ING1
      negative expression. CONCLUSIONS: P33ING1 expression decrease in ACC, which may
      play an important role in the carcinogenesis and progression of ACC. P33ING1 and
      P53 may have an synergistic effect of suppressing cell growth and accelerating
      cell apoptosis.

PMID- 16886120
TI  - [Changes of trace elements in regional lymph nodes of gastric carcinoma].
AB  - OBJECTIVE: To explore the relationship between the changes of trace elements and
      lymphatic metastasis in gastric carcinoma. METHODS: Trace elements including Fe,
      Mg, Mn, Ca, Cu, Zn, Se were measured in primary gastric carcinoma and regional
      lymph nodes from 40 patients with gastric carcinoma, and compared among the
      primary tumor, metastatic, and non-metastatic nodes. RESULTS: There were no
      significant differences in the contents of Fe, Mg, Mn and Ca among primary
      gastric tumors, regional lymph nodes with or without metastasis (P=0.372 - 0.741,
      P > 005), and no significant differences in the contents of all 7 trace elements
      between primary tumors and metastatic lymph nodes (P=0.15 - 0.59, P > 005).
      Compared with metastatic lymph nodes, the contents of Zn, Se significantly
      decreased, while Cu and Cu/Zn significantly increased (P=0.001 - 0.009, P< 0.01)
      in non-metastatic lymph nodes. The content of Zn in N2 positive lymph nodes was
      significant lower than that in N1 positive nodes (P=0.027). There were no
      significant difference in the contents of all 7 elements between intestinal type
      and diffuse type (P=0.149 - 0.758, P > 0.05). CONCLUSIONS: Lymphatic metastasis
      of gastric cancer is concomitant with the changes of trace elements, and the
      changes of Zn, Cu, Se may be related with lymphatic metastasis.

PMID- 16886121
TI  - [Inhibitive effects of gastric cancer cell-dendritic cell fusion vaccine on tumor
      cell proliferation cycle].
AB  - OBJECTIVE: To study the inhibitive effects of gastric cancer cell-dendritic cell
      fusion vaccine on tumor cells of proliferation cycle. METHODS: Peripheral blood
      mononuclear cells were separated from gastric cancer patients and co-cultured
      with granulocyte macrophage colony stimulating factors(GM-CSF), interleukin-4(IL
      4) and tumor necrosis factor-alpha(TNF-alpha) to generate mature dendritic cells.
      The dendritic cells and SGC7901 cells were fused by polyethylene glycol, and the
      pure fusion cells were screened out by selective culture systems. The inhibitive
      effects of gastric cancer cell-dendritic cell fusion vaccines on tumor cell
      proliferation cycle in vivo and in vitro were detected by flow cytometry.
      RESULTS: Treated with the fusion vaccine in vitro, the percentages of G(0)/G(1),
      S and G(2)/M cells of tumor cells were (76.77+/- 4.38)%, (16.50+/- 2.90)% and
      (6.73+/- 1.59)% respectively. There were significant differences in the
      percentages of different cell cycle tumor cells between the tumor cells treated
      with the fusion vaccine and those co-cultured with dendritic cell or T cells
      alone(P< 0.01). The proliferative index of the tumor cells treated with the
      fusion vaccine was 23.34+/- 3.51, significantly lower than those co-cultured with
      dendritic cell and controls (P< 0.05). CONCLUSIONS: Fusion vaccines can affect
      cell cycle of the tumor cells, thus inhibit tumor cell proliferation and growth.

PMID- 16886122
TI  - [Relationship of hypoxia-induced factor with tumor angiogenesis in early liver
      metastasis in colonic cancer].
AB  - OBJECTIVE: To study the relationships of hypoxia-induced factor (HIF) with tumor
      angiogenesis and early liver metastasis in colonic cancer. METHODS: Thirty three
      cases of colon cancer undergoing radical surgery were divided into two groups
      according to liver metastasis or not within half a year after operation.
      Expressions of HIF and vascular endothelial growth factor (VEGF) were examined
      using immunohistochemical method and tumor microvessel density (MVD) was measured
      in colonic cancer specimens. RESULTS: Fifteen cases developed early liver
      metastasis, while 18 did not. The positive rates of HIF and VEGF, and MVD were
      86.7%, 66.7%, (57.9+/- 12.7)% respectively in the group with early liver
      metastasis, significantly higher than 44.4% (P< 0.05), 27.8% (P< 0.05) and
      (22.3+/- 10.2)% (P< 0.01) respectively in the group without early liver
      metastasis respectively. CONCLUSION: HIF can promote tumor angiogenesis in
      colonic cancer, and is closely related with early liver metastasis.

PMID- 16886123
TI  - Percutaneous angioplasty of chronically occluded coronary arteries: long-term
      clinical follow-up.
AB  - BACKGROUND: Percutaneous coronary intervention (PCI) of a chronic total occlusion
      (CTO) is one of the most demanding procedures in interventional cardiology. In
      spite of growing experience and technological progress, efficacy of PCI of CTO
      remains lower than that of standard PCI. AIM: To evaluate long-term clinical
      results of PCI in patients with stable angina and CTO. METHODS: The study
      involved 459 consecutive patients who underwent the procedure of CTO
      recanalisation between 1996 and 2003. All procedures were performed using the
      standard technique. Follow-up examination was carried out based on a written
      questionnaire, and the mean follow-up period was 30+/-18 months. RESULTS: The
      average success rate of intervention was 64.9% and 63.8% of patients underwent
      successful and uneventful procedures. Clinically significant in-hospital
      complications were noted in 8 (1.6%) patients including 1 (0.2%) death, 2 (0.4%)
      cases of myocardial infarction and 4 (1.0%) repeated revascularisations. Long
      term survival following either successful or failed recanalisation was similar
      (97.5% vs 97.3%, NS) as was incidence of acute coronary syndromes (12.5% vs
      12.1%, respectively; NS). Patients after successful recanalisation less
      frequently underwent surgical revascularisation (3.6% vs 8.1%, respectively; p
      <0.05) and also suffered less frequently from angina (CCS 0/CCS I: 20.4% vs
      12.1%, p <0.00005). Otherwise, they were at higher risk of repeated PCI due to
      restenosis (13.2% vs 6.7%, respectively; p <0.05). CONCLUSIONS: Success rate of
      PCI in patients with chronically occluded coronary arteries and stable angina is
      moderately high with relatively low incidence of complications. Late benefits
      from successful recanalisation of coronary artery depend predominantly on
      improved coronary reserve and decreased need for surgical myocardial
      revascularisation. Successful recanalisation does not reduce the risk of death or
      myocardial infarction but is associated with higher frequency of repeated PCI due
      to restenosis.

PMID- 16886124
TI  - Influence of pathogenetic factors on prognosis in patients with native valve
      infective endocarditis.
AB  - INTRODUCTION: Despite improvement in medical care the incidence of infective
      endocarditis (IE) has not decreased. Positive blood cultures are one of the most
      important diagnostic criteria of IE. There are no uniform data regarding the
      influence of pathogenetic factors on prognosis. AIM: To analyse the results of
      blood and valve cultures in patients with IE of native valves and evaluate their
      influence on the risk of early and late deaths as well as recurrence of IE.
      METHODS: The study group consisted of 152 patients with IE of native valves. The
      IE diagnosis was based on the Duke criteria. Early and late mortality as well as
      recurrence of IE were analysed in patients hospitalised at the Institute of
      Cardiology in Warsaw from 1988 to 1998. RESULTS: Positive blood cultures were
      found in 103 (67.8%) of patients. In-hospital mortality was 5.9% (9 deaths). The
      incidence of early deaths was significantly lower in surgically treated patients
      (p=0.01). Late deaths occurred in 23 (16%) patients. Results of blood and valve
      tissue cultures were not related to mortality. Recurrent IE was observed in 7
      (4.9%) patients. Staphylococcus aureus was an independent risk factor for
      recurrent IE (p=0.04). Six-year survival was 79%. CONCLUSIONS: In patients with
      native valve infective endocarditis: 1. The risk of early and late death is not
      related to the results of blood and valve cultures. 2. Staphylococcus aureus
      aetiology increases the risk of disease recurrence. 3. The risk of early death is
      significantly lower in patients treated with surgery.

PMID- 16886125
TI  - Hospital readmission in patients with implantable cardioverter-defibrillators.
AB  - INTRODUCTION: Hospital readmissions are one of the important problems of patients
      with implantable cardioverter-defibrillators (ICD). Detailed analysis of the
      causes of re-hospitalizations may lead to improved management of ICD patients and
      eventually limit the number of hospital readmissions. AIM: Prospective analysis
      of repeat hospitalisations, their causes and time from discharge to first
      hospital readmission in a group of patients after ICD implantation. A search for
      predictors of rehospitalisation was also performed. METHODS: Analysis involved
      133 consecutive patients who underwent ICD implantation in the Department of
      Cardiology, PAM. Readmission causes were split into cardiac and non-cardiac. An
      index of repeat hospitalisation was calculated and parameters with a direct
      impact on rehospitalisation necessity were also evaluated. RESULTS: One hundred
      and sixty-seven hospital readmissions of 72 (54%) patients were noted at mean
      22+/-15 months after the primary hospitalisation. Rehospitalisation index per
      patient for the total follow-up period was 1.26, while for the first year of
      follow-up it was 0.69. In the case of 42 (32%) patients, 91 (54.5%) hospital
      readmissions were associated with arrhythmia. In 34 (25.6%) patients, 54 (32.3%)
      re-hospitalizations were not related to arrhythmia, while 20 (15%) patients were
      hospitalised 22 times (13.2%) for non-cardiac reasons. Mean time to the first
      readmission, regardless of the reason, was 9+/-9 months. Predominant causes of
      repeat hospitalisation were ventricular arrhythmias and worsening of heart
      failure. Patients with left ventricular ejection fraction (LVEF) below 30% and in
      functional NYHA class III were readmitted to hospital more frequently for reasons
      not related to arrhythmia. CONCLUSIONS: Hospital readmissions for cardiac causes
      in patients after ICD implantation are still frequent. Most of them are caused by
      ventricular arrhythmia and heart failure. Low LVEF (<30%) and NYHA functional
      class > or =III are risk factors predicting repeat hospitalisations unrelated to
      arrhythmia.

PMID- 16886126
TI  - Relationship between aortic valve calcification and aortic atherosclerosis: a
      transoesophageal echocardiography study.
AB  - INTRODUCTION: Clinical and laboratory data provide an increasing amount of
      information regarding the common aetiopathogenetic background of acquired heart
      defects with calcification and arterial atherosclerosis. AIM: To evaluate the
      relationship between presence and severity of calcifications of the aortic
      semilunar valves and the intensity of atherosclerotic lesions in the aorta and
      aortic stiffness (AS). METHODS: The study group comprised 80 subjects (49 males
      and 31 females) aged 72.2 (+/-8.0) years with an aortic valve defect found on
      echocardiography. Patients were divided into two subgroups depending on the
      severity of valvular disease. Subgroup I comprised 42 patients with small
      valvular lesions (0--absence of calcification of the valve, or +--trivial
      valvular calcifications, possible to find on detailed evaluation of the valve).
      Subgroup II consisted of 38 patients with intense calcifications (++--large,
      easily found valve calcifications, +++--massive calcifications affecting leaflet
      mobility). All patients underwent transoesophageal echocardiography to evaluate
      atherosclerotic lesions in the aorta. The assessment included the following:
      location of the lesions in the aorta, intimal thickness, presence of
      calcifications and mobile parts of plaques and possible associated thrombi.
      Aortic stiffness was also measured using the formula: AS=log (SBP/DBP)/Ao(max)
      Ao(min)/Ao(min). RESULTS: Atherosclerotic plaques were more frequent in patients
      with more prominent calcifications of the aortic valve (19 vs 10 patients, p
      <0.05). Intimal thickness was larger in patients with more pronounced valve
      calcifications (3.9+/-0.8 mm vs 2.2+0.6 mm, p <0.05). Presence of calcifications
      in the aortic wall was also more frequent in patients from group II, as they were
      found in 10 subjects compared to only 3 cases in group I. Mobile plaque parts
      were observed in 3 patients from group II; also thrombi were found in 3
      individuals from this group. Patients with more prominent calcifications of the
      aortic valve had decreased aortic wall elasticity (AS 5.5+/-1.2 cm vs 3.4+/-0.9
      cm, p <0.05). CONCLUSIONS: Severity of aortic valve calcification indicates
      simultaneous changes in the thoracic aorta. Stiffness of the aortic wall is
      greater in patients with a more pronounced defect of the aortic valve. Prevalence
      of atherosclerosis risk factors is increased in patients with aortic valve
      defect, enhanced atherosclerosis and rigidity of the aorta. Defect of the aortic
      valve and increased aortic rigidity may be different manifestations of
      atherosclerosis.

PMID- 16886127
TI  - The prognostic value of renal dysfunction in patients with chronic heart failure:
      12-month follow-up.
AB  - INTRODUCTION: Renal function assessment is an important element of management and
      therapeutic decision-making in patients with chronic heart failure (CHF). AIM: To
      evaluate the prognostic value of renal dysfunction in patients with CHF in 12
      month follow-up. METHODS: 639 consecutive patients hospitalised in our department
      from 1 July 2002 to 31 December 2003 with diagnosis of CHF (NYHA II-IV), based on
      medical records, were initially enrolled in the study. Patients underwent one
      year follow-up. Finally, 498 patients, aged 22-98 years (mean age 69+/-12 years)
      in whom creatinine concentration was measured and creatinine clearance was
      estimated at admission with the Cockroft-Gault quotation and with long-term
      follow-up results obtained, were enrolled in the study. Patients were divided
      into two groups according to the creatinine level: Group I without renal
      dysfunction (creatinine level <1.4 mg/dl), and Group II--with renal dysfunction
      (creatinine level >1.4 mg/dl). RESULTS: Patients with renal dysfunction were
      significantly older and more likely to be male and in NYHA class III-IV (p
      <0.001). Analysis of pharmacotherapy for CHF revealed that patients with renal
      impairment significantly less frequently received beta-blockers (67% vs 81%, p
      <0.005), angiotensin-converting enzyme inhibitors (68% vs 82%, p <0.005) and
      combined treatment of beta-blocker and angiotensin-converting enzyme inhibitor
      (56% vs 71%, p <0.05), whereas loop diuretics were more frequently prescribed in
      this group (80% vs 70%, p <0.05). In patients with renal dysfunction, there was a
      significantly higher mortality rate at 30 days (32% vs 14%, p <0.001) as well as
      at 12 months (45% vs 20%, p <0.001). The incidence of re-hospitalisation for
      cardiovascular reasons (CHF worsening, myocardial infarction, stroke) was
      significantly higher in patients with renal dysfunction (70% vs 55%, p <0.005).
      Multivariate analysis of all factors affecting one-year mortality demonstrated
      that renal dysfunction is a strong and independent risk factor for death in
      patients with CHF (RR=2.13, 95% CI: 1.31-3.45; p <0.05) and it increases the risk
      of re-hospitalisation (RR=1.53, 95% CI: 1.01-2.14; p <0.05). CONCLUSIONS: Renal
      dysfunction is an independent prognostic factor in patients with CHF, which
      allows identification of a high-risk group and administration of optimal therapy,
      which in turn can result in a reduction of mortality.

PMID- 16886129
TI  - [Successful percutaneous angioplasty of renal artery in a patient with severe
      arterial hypertension and symptoms of hyperaldosteronism: a case report].
AB  - Arterial hypertension may result from renal artery stenosis. In this type of
      hypertension renin-angiotensin-aldosterone system is activated and patients often
      produce signs of hyperaldosteronism. It must be distinguished from primary
      hyperaldosteronism in order to chose a proper therapy. In this paper we describe
      a case of a 65-years-old man with severe arterial hypertension, which was
      difficult to control pharmacologically. The patient revealed symptoms which
      suggested primary hyperaldosteronism (except normal plasma renin activity). Only
      imaging techniques allowed diagnose of renal artery stenosis and carry out
      successful percutaneous angioplasty of renal artery.

PMID- 16886128
TI  - The use of myocardial contrast echocardiography in the assessment of left
      ventricular function recovery after primary percutaneous coronary intervention in
      the setting of acute myocardial infarction.
AB  - BACKGROUND: Despite successful reperfusion therapy of acute myocardial infarction
      and complete restoration of infarct-related artery patency, the improvement of
      systolic function in long-term outcome depends on preserved microvasculature
      integrity. Myocardial contrast echocardiography (MCE) is a useful technique for
      identification of viable myocardium. AIM: To assess the value of real-time
      myocardial contrast echocardiography (rt-MCE) in prediction of left ventricular
      function improvement in patients with anterior wall acute myocardial infarction
      as well as selection of the optimal cut-off value for the number of dysfunctional
      segments with preserved complete perfusion, in order to predict the global left
      ventricular function improvement during one-month observation. METHODS: Rt-MCE
      was performed in 74 patients (50 men, aged 58+/-11 years) with anterior wall
      myocardial infarction, treated with primary percutaneous coronary intervention
      (PCI) within 12 hours from the onset of symptoms. After estimation of regional
      contractility disturbances and global systolic function of the left ventricle, rt
      MCE was performed with contrast assessment of dysfunctional segments (normal
      contrast pattern=2, heterogeneous=1, lack of contrast=0). Regional perfusion
      score index (RPSI) was calculated by adding the perfusion indices and dividing by
      the number of dysfunctional segments. RESULTS: Of a total of 1184 visualised
      segments, 344 (29.1%) were dysfunctional (189 hypokinetic, 155 akinetic).
      Contractility improvement was observed in 192 segments (preserved viability in
      105 hypokinetic and 37 akinetic segments). In a group of 44 patients with
      systolic function improvement, 34 of them had preserved viability, and in a group
      of 30 patients without LVEF improvement, in 22 of them myocardium viability was
      not observed. Sensitivity, specificity and accuracy of rt-MCE in prediction of
      left ventricular global improvement were 72.7%, 73.3% and 73%, respectively,
      whereas in prediction of regional function improvement these values were 73.9%,
      77% and 75.5%, respectively. CONCLUSION: Rt-MCE performed in the early phase of
      myocardial infarction enables the prediction of left ventricular regional and
      global function improvement in patients treated with primary PCI.

PMID- 16886130
TI  - [Syncope as a first manifestation of Prinzmetal's angina in a 49-year-old woman.
      A case report].
AB  - A case of a 49-year-old woman with episodes of syncopes as a first manifestation
      of variant angina is presented. She was admitted to cardiology ward because of
      recurrent angina associated with marked ST segment elevation in the inferior and
      anterior electrocardiographic leads. Previously she was diagnosed at a
      neurological ward because of nocturnal syncopes without accompanying chest pain
      but with associated hypotonia and bradycardia of about 36 beats/min. Coronary
      arteriography revealed non-significant coronary stenosis of two vessels (left and
      right coronary artery) and coronary spasm close to these obstructions. Therapy
      with calcium channel blockers as well as giving up smoking eliminated the
      episodes of chest pain and syncope in a twelve-month follow-up.

PMID- 16886132
TI  - [Mitral valve insufficiency in a 2.5-year-old girl as a result of endocarditis? A
      case report].
AB  - We present a case of a 2.5-year-old girl with a history recurrent pneumonia,
      followed by decreased physical capacity. Echocardiography showed severe (grade
      IV) mitral regurgitation with anterior leaflet perforation. The patient was
      selected for cardiac surgery. The possibility of endocarditis as a cause of
      mitral valve insufficiency is discussed.

PMID- 16886131
TI  - [Myocardial microabscesses detected by endomyocardial biopsy in a patient with
      dilated cardiomyopathy and celiac disease: a case report].
AB  - A case of an 18-year-old male with a one-month history of progressive heart
      failure and suspected viral myocarditis is presented. Myocardial biopsy revealed
      mononuclear infiltration and the presence of granulocytes with micro-abscesses.
      Small bowel biopsy and autoimmunological examinations documented the presence of
      celiac disease. The patient's condition gradually improved following antibiotics,
      standard heart failure treatment, dental caries therapy and introduction of
      gluten-free diet.

PMID- 16886133
TI  - [Pulmonary embolism in patients with atrial fibrillation. How to recognize it? Is
      it worth recognition, and what do these both diseases have in common?].

PMID- 16886134
TI  - [Cor triatriatum in 13-year-old asymptomatic boy. A case report].

PMID- 16886135
TI  - [Uni-directional atrioventricular block].

PMID- 16886136
TI  - [Complex percutaneous coronary intervention of left main coronary artery in
      patient with acute myocardial infarction complicated with cardiogenic shock].

PMID- 16886137
TI  - [Eleven-years long follow-up in a patient after myocardial infarction, with low
      ejection fraction and recurrent ventricular tachycardia. The role of implantable
      cardioverter defibrillator and selective ablation].
AB  - The selective ablation of the recurrent ventricular tachycardia (VT) in a 75-year
      old patient after extensive inferior myocardial infarction (24 years ago), with
      low ejection fraction was performed. In 1995 the cardioverter-defibrillator was
      implanted due to recurrent, symptomatic VT. The coronary angiography in 1995 and
      in 2006 revealed the occlusion of the right coronary and the circumflex arteries.
      One year after implantation, he had electrical storm caused by proarrhythmic
      effect of amiodarone with prolongation of QT/QTc interval. During follow up
      episodes of VT (approximately 5/year) were successfully terminated by ATP and
      rarely by cardioversion. Recently, the patient was admitted to the hospital
      because of the very frequent (25/day) episodes of slow (500-560 ms), sustained
      ventricular tachycardia. The pharmacological treatment was unsuccessful. CARTO
      mapping and entrainment pacing revealed VT circuit around mitral annulus. A few
      applications at the paraseptal part of the mitral isthmus terminated VT, which
      was no longer inducible. During following days there were no VTs requiring ICD
      interventions.

PMID- 16886139
TI  - [Reimbursement of drug expenses--unseen problem, increasing threats].

PMID- 16886141
TI  - Management of persistent bacteremia caused by methicillin-resistant
      Staphylococcus aureus: a survey of infectious diseases consultants.
AB  - We conducted a survey in 2005 of infectious diseases consultants and asked about
      persistent bacteremia due to methicillin-resistant Staphylococcus aureus. Many
      consultants perceived an increase in the frequency of illness, and, when
      presented with vancomycin minimum inhibitory concentrations approaching the limit
      of the susceptible range, most consultants indicated that they would switch to
      newer antimicrobial agents for treatment.

PMID- 16886140
TI  - [Inflammatory response after coronary angioplasty - mechanisms and significance].

PMID- 16886142
TI  - Cerebral aneurysmal arteriopathy associated with HIV infection in an adult.
AB  - Human immunodeficiency virus (HIV)-associated cerebral aneurysmal arteriopathy is
      described in the pediatric medical literature and features diffuse fusiform
      aneurysms of the arteries of the circle of Willis. We present the first report
      (to our knowledge) of this disease entity in an adult, a 29-year-old woman with
      acquired immunodeficiency syndrome who presented with subarachnoid hemorrhage.

PMID- 16886143
TI  - Botulism in patients who inhale cocaine: the first cases in France.
AB  - We describe 2 cases of mild botulism in patients who inhaled cocaine. Botulism,
      though rare, is increasing in incidence among illicit drug users. To our
      knowledge, these are the first cases of botulism in illicit drug users in France.
      Clinicians should be aware of this phenomenon; botulism should be considered in
      illicit drug users with neurological symptoms.

PMID- 16886144
TI  - Prospective, randomized inpatient study of oral metronidazole versus oral
      metronidazole and rifampin for treatment of primary episode of Clostridium
      difficile-associated diarrhea.
AB  - BACKGROUND: To date, no randomized trial to address the use of adjunctive
      rifampin in addition to metronidazole for the treatment of Clostridium difficile
      associated diarrhea has been reported. Rifampin has excellent in vitro activity
      against C. difficile and penetrates into cellular materials where the organisms
      may persist. METHODS: This was a prospective, randomized, single-blinded study of
      39 patients that compared therapy with metronidazole alone versus therapy with
      metronidazole and rifampin for 10 days to treat laboratory-confirmed primary
      episode C. difficile-associated diarrhea. Twenty patients were randomly assigned
      to the metronidazole group, and 19 were randomly assigned to the metronidazole
      and rifampin group. Data were analyzed by intention-to-treat analysis using the 2
      tailed Kaplan-Meier method and the log-rank test. RESULTS: Adjunctive rifampin
      treatment for 10 days, compared with treatment with metronidazole alone for 10
      days, was associated with a similar median time to symptom improvement (9.0 days
      vs. 6.5 days; P=.74), a similar median time to first relapse (26 days vs. 16
      days; P=.23), a similar proportion of patients with relapse by study day 40 (42%
      vs. 38%; P=1.0), and a similar proportion of patients experiencing nonfatal
      adverse events (37% vs. 40%; P=.55). There were a significantly higher number of
      deaths in the metronidazole and rifampin group, compared with the metronidazole
      group (6 of 19 patients vs. 1 of 20 patients; P=.04), but there were fewer
      laboratory-confirmed relapses by study day 40 (2 vs. 4; P=.66). CONCLUSIONS: We
      conclude that there is no role for routine rifampin as an adjunct to treatment
      with metronidazole for hospitalized patients with C. difficile-associated
      diarrhea. The cure rates for both treatment groups remain unacceptably low, and
      better treatments are urgently needed.

PMID- 16886145
TI  - Improving the treatment of Clostridium difficile-associated disease: where should
      we start?

PMID- 16886146
TI  - Enteroaggregative Escherichia coli is a cause of acute diarrheal illness: a meta
      analysis.
AB  - BACKGROUND: Conflicting studies exist regarding the role of enteroaggregative
      Escherichia coli (EAEC) as a cause of acute diarrheal illness. The objective of
      this meta-analysis was to determine whether identification of EAEC in stool
      samples is associated with acute diarrheal illness among different
      subpopulations, by geographic area. METHODS: A comprehensive search of electronic
      bibliographic databases (Medline and PubMed) from August 1985 to January 2006, as
      well as a search of conference proceedings, references of articles, and contacts
      with investigators of EAEC, yielded 354 studies. RESULTS: Forty-one studies (12%)
      that met the selection criteria (i.e., that examined the association between
      acute diarrheal illness and the excretion of EAEC among different subpopulations)
      were included. In this meta-analysis, presence of EAEC identified with the HEp-2
      cell adherence assay was found to be significantly associated with acute
      diarrheal illness among children residing in developing regions (odds ratio [OR],
      1.58; 95% confidence interval [CI], 1.36-1.83) and industrialized regions (OR,
      1.23; 95% CI, 1.03-1.48), adults with human immunodeficiency virus infection
      residing in developing regions (OR, 6.43; 95% CI, 2.91-14.16), adults residing in
      developing regions (OR, 7.15; 95% CI, 1.96-26.04), and international travelers to
      developing regions (OR, 6.72; 95% CI, 2.62-17.20). A limited number of studies
      were available that examined the role of EAEC identified by its virulence genes
      by a DNA probe. CONCLUSIONS: On the basis of this meta-analysis, we conclude that
      EAEC is a cause of acute diarrheal illness among many different subpopulations in
      both developing and industrialized regions, that EAEC strains are very
      heterogeneous and that additional studies that examine the role of EAEC in acute
      diarrheal illness are needed.

PMID- 16886147
TI  - Symptomatic predictors of influenza virus positivity in children during the
      influenza season.
AB  - BACKGROUND: Symptomatic predictors of the etiology of infectious diseases are
      necessary when quick action is required in treatment, as with cases of influenza
      or anthrax, or for when patient isolation is required, as with cases of severe
      acute respiratory syndrome (SARS). Predictors of influenza virus infection during
      the influenza season have previously been evaluated in adult studies of the
      antiviral agent zanamivir; cough and temperature > or =37.8 degrees C predicted
      influenza virus positivity in 79% of those evaluated. METHODS: Fever and other
      respiratory symptoms were examined to determine their value in predicting
      influenza virus-positive status in children. Data analyzed were from a clinical
      trial of zanamivir in children 5-12 years of age and from a trial of oseltamivir
      in children 1-12 years of age. RESULTS: In the pediatric study of zanamivir, as
      in the adult zanamivir study, cough and fever were the best predictors of
      influenza virus infection; a temperature > or =38.2 degrees C plus cough
      predicted 83% (95% CI, 79%-88%) of illnesses that were determined to be influenza
      virus positive. Cough (positive predictive value, 70%; 95% CI, 64%-75%), but not
      fever, was the best predictor of influenza virus-positive status in children aged
      5-12 years in the oseltamivir trials, but neither cough nor fever were successful
      predictors in young children 1-4 years of age. The latter findings appeared to be
      the result of less symptomatic diversity among patients recruited for this trial,
      such that subjects who were determined to be influenza virus positive and
      subjects who were influenza virus negative had similar symptoms. CONCLUSIONS: The
      results of these studies suggest that, during the influenza season, symptomatic
      predictors of influenza virus infection are applicable to identification of cases
      in children, although confirmation of predictive values in subjects 1-4 years of
      age may require further study of additional signs/symptoms.

PMID- 16886148
TI  - Clinical and epidemiological analyses of human pythiosis in Thailand.
AB  - BACKGROUND: Pythiosis is an emerging and life-threatening infectious disease in
      humans and animals that is caused by the pathogenic oomycete Pythium insidiosum.
      Human pythiosis is found mostly in Thailand, although disease in animals has been
      increasingly reported worldwide. Clinical information on human pythiosis is
      limited, and health care professionals are unfamiliar with the disease, leading
      to underdiagnosis, delayed treatment, and poor prognosis. METHODS: To
      retrospectively study the clinical and epidemiological features of human
      pythiosis, we analyzed clinical data from patients with pythiosis diagnosed
      during the period of January 1985 through June 2003 at 9 tertiary care hospitals
      throughout Thailand. RESULTS: A total of 102 cases of human pythiosis were
      documented nationwide. A substantial proportion (40%) of cases occurred in the
      last 4 years of the 18-year study interval. Clinical presentations fell into 4
      groups: cutaneous/subcutaneous cases (5% of cases), vascular cases (59%), ocular
      cases (33%), and disseminated cases (3%). Almost all patients with
      cutaneous/subcutaneous, vascular, and disseminated pythiosis (85%) had underlying
      thalassemia-hemoglobinopathy syndrome. Most ocular cases (84%) were associated
      with no underlying disease. A majority of the patients were male (71%), were aged
      20-60 years (86%), and reported an agricultural occupation (75%). Regarding
      treatment outcomes, all patients with disseminated infection died; 78% of
      patients with vascular disease required limb amputation, and 40% of these
      patients died; and 79% of patients with ocular pythiosis required
      enucleation/evisceration. CONCLUSIONS: Here, we report, to our knowledge, the
      largest case study of human pythiosis. The disease has high rates of morbidity
      and mortality. Early diagnosis and effective treatment are urgently needed to
      improve clinical outcomes. Because P. insidiosum is distributed worldwide and can
      infect healthy individuals, an awareness of human pythiosis should be promoted in
      Thailand and in other countries.

PMID- 16886149
TI  - Comparison of epidemiological, clinical, and biological features of invasive
      aspergillosis in neutropenic and nonneutropenic patients: a 6-year survey.
AB  - BACKGROUND: Invasive aspergillosis is an opportunistic infection that occurs
      mainly among patients with prolonged neutropenia. Few data are available on
      invasive aspergillosis in nonneutropenic patients. METHODS: The aim of this
      survey was to compare neutropenic and nonneutropenic patients who had received a
      diagnosis of invasive aspergillosis at our institution during a 6-year period.
      RESULTS: Among the 88 cases of invasive aspergillosis analyzed here, 12 were
      histologically proven, 52 were probable, and 24 were possible. Forty-seven
      percent of cases were diagnosed in the intensive care unit, and 40% were
      diagnosed in hematology units. Neutropenia was a risk factor for 52 patients
      (59%), most of whom had hematological or solid malignancies. Among the 36
      nonneutropenic patients (41%), the main underlying conditions were steroid
      treated chronic obstructive pulmonary disease, asthma, rheumatoid arthritis,
      giant-cell arteritis, and microvascular disorders; 10 patients were recipients of
      solid-organ transplants, and 1 patient was seropositive for human
      immunodeficiency virus. The distribution of proven and probable invasive
      aspergillosis was similar for neutropenic and nonneutropenic patients. The
      mortality rate was 71.5% overall and was significantly higher among
      nonneutropenic patients than among neutropenic patients (89% vs. 60%; P<.05).
      Compared with neutropenic patients, nonneutropenic patients were significantly
      less likely to have symptoms of invasive aspergillosis and more likely to have
      frequent intercurrent pneumonia due to another microorganism. The sensitivity of
      mycological examination of bronchoalveolar lavage fluid specimens was higher for
      nonneutropenic patients than for neutropenic patients (85% vs. 58%; P<.05),
      whereas the sensitivity of antigenemia was the same for the 2 populations (65%
      vs. 64%). Findings on thoracic computed tomographs were similar, except that
      segmental areas of consolidation occurred more frequently among neutropenic
      patients. CONCLUSION: This survey at a whole institution underlines the high
      number of cases of invasive aspergillosis among nonneutropenic patients, with an
      overall mortality rate that was significantly higher than that for neutropenic
      patients.

PMID- 16886150
TI  - The association of newly identified respiratory viruses with lower respiratory
      tract infections in Korean children, 2000-2005.
AB  - BACKGROUND: This study was performed to evaluate the associations of newly
      recognized viruses, namely, human metapneumovirus (hMPV), human coronavirus
      (HCoV)-NL63, and human bocavirus (HBoV) with lower respiratory tract infections
      (LRTIs) in previously healthy children. METHODS: To determine the prevalences of
      11 viruses--respiratory syncytial virus (RSV), adenovirus, rhinovirus,
      parainfluenza viruses (PIVs) 1 and 3, influenza viruses A and B, hMPV, HCoV, HCoV
      NL63, and HBoV--among infants or children with LRTIs, in association with their
      epidemiologic characteristics, we performed multiplex reverse-transcriptase
      polymerase chain reaction on nasopharyngeal aspirates obtained from 515 children
      < or =5 years old with LRTIs during the period 2000-2005. RESULTS: Viruses were
      identified in 312 (60.6%) of the 515 patients. RSV was detected in 122 (23.7%),
      HBoV in 58 (11.3%), adenovirus in 35 (6.8%), PIV-3 in 32 (6.2%), rhinovirus in 30
      (5.8%), hMPV in 24 (4.7%), influenza A in 24 (4.7%), PIV-1 in 9 (1.7%), influenza
      B in 9 (1.7%), and HCoV-NL63 in 8 (1.6%). Coinfections with > or =2 viruses were
      observed in 36 patients (11.5%). Twenty-two patients (37.9%) infected with HBoV
      had a coinfection. Bronchiolitis was frequently diagnosed in patients who tested
      positive for RSV, PIV-3, or rhinovirus, whereas influenza A, PIV-1, and HCoV-NL63
      were commonly found in patients with croup. The age distributions of patients
      with viral infections differed; notably, RSV was responsible for 77% of LRTIs
      that occurred in infants < or =3 months old. The number of hMPV infections peaked
      between February and April, whereas the number of HCoV-NL63 infections peaked
      between April and May. CONCLUSIONS: This study describes the features of LRTIs
      associated with newly identified viruses in children, compared with those
      associated with known viruses. Additional investigations are required to define
      the role of HBoV in LRTI.

PMID- 16886151
TI  - Association of polymorphisms of IGF1R and genes in the transforming growth factor
      beta /bone morphogenetic protein pathway with bacteremia in sickle cell anemia.
AB  - Infection and bacteremia are common in sickle cell disease. We hypothesized that,
      consistent with evidence for the genetic modulation of other disease
      complications, the risk of developing bacteremia might also be genetically
      modulated. Accordingly, we studied the association of single nucleotide
      polymorphisms (SNPs) in candidate genes with the risk of bacteremia in sickle
      cell anemia. We found significant associations with SNPs in IGF1R and genes of
      the TGF-beta /BMP pathway (BMP6, TGFBR3, BMPR1A, SMAD6 and SMAD3). We suggest
      that both IGF1R and the TGF-beta /BMP pathway could play important roles in
      immune function in sickle cell anemia and their polymorphisms may help identify a
      "bacteremia-prone" phenotype.

PMID- 16886152
TI  - An outbreak of cadaver-acquired chickenpox in a health care setting.
AB  - The varicella-zoster virus (the chickenpox virus) is highly infectious and may
      affect nonimmune health care professionals. We report an outbreak of chickenpox
      in our hospital in which the source of infection was a cadaver. The spread of
      infection occurred in the course of an autopsy.

PMID- 16886153
TI  - Infectious diseases and the autopsy.

PMID- 16886155
TI  - Milk of nonhuman origin and infectious diseases in humans.
AB  - Milk and milk products from domestic animals, which are potential infectious
      hazards, are made more so by modern milk production, because milk from thousands
      of animals is often pooled prior to bottling or before manufacturing derivative
      products. Thus, contaminated milk from 1 animal can result in a widespread
      problem. Pasteurization largely eliminates this hazard. Most disease transmission
      caused by contamination of the milk supply has been eliminated by hygienic
      production measures and pasteurization. However, contamination may occur after
      pasteurization, and no process works perfectly all of the time. Despite
      scientific opinion that pasteurized products are safer than raw ones--and are
      equally nutritious--segments of the population regard raw milk products as more
      nutritious and better tasting than pasteurized milk products. Thus, low levels of
      raw milk consumption persist in the United States and other developed nations.
      Occasional milk-associated disease outbreaks caused by raw milk consumption or by
      breakdowns in the proper production of pasteurized products still occur.

PMID- 16886154
TI  - Childhood cryptosporidiosis is associated with a persistent systemic inflammatory
      response.
AB  - Cryptosporidiosis in young children prompts local inflammation in the intestinal
      tract. We studied a cohort of young children with cryptosporidiosis to determine
      whether systemic inflammatory responses occur and, if so, to evaluate whether
      inflammation persists after infection. Cryptosporidiosis was associated with
      increased levels of interleukin-8 and tumor necrosis factor- alpha systemically,
      which persisted at 6 months after enrollment. The level of intestinal tumor
      necrosis factor- alpha was elevated at enrollment, but elevated levels did not
      persist. Worsening of malnutrition, particularly stunting, was observed after
      infection. The association of cryptosporidiosis, inflammation, and stunting in
      children with cryptosporidiosis warrants further evaluation.

PMID- 16886156
TI  - Potential confounding in evaluating infection-control interventions in hospital
      settings: changing antibiotic prescription.
AB  - The colonization dynamics of antibiotic-resistant pathogens in hospital settings
      are complex, with multiple and continuously interacting variables (e.g.,
      introduction of resistance, infection-control practices, antibiotic use).
      Quantification of these variables is indispensable in the evaluation of
      intervention studies, because these variables represent potential confounders. In
      this article, the complexity of colonization dynamics is described. Through a
      systematic review, we identified studies that evaluated the modification of
      antibiotic prescription to reduce antibiotic resistance in intensive care units
      (n=19), and the extent of confounding-control was determined. Most studies
      evaluated antimicrobial restriction/substitution (n=12) or antibiotic rotation
      (n=4). Sixteen studies had a prospective cohort design (before-after), of which
      12 were without a control group. Introduction of antibiotic resistance was
      determined in 10 studies. The relative importance of colonization routes and
      adherence to infection-control measures were not determined in any study.
      Therefore, it remains uncertain whether observed changes in the prevalence of
      antibiotic resistance after intervention were causally related to the
      intervention. Appropriate choices of study design, primary end point
      (colonization rates rather than infection rates) and statistical tests,
      determination of colonization routes, and control of potential confounders are
      needed to increase validity of intervention studies.

PMID- 16886157
TI  - Genital human papillomavirus infection.
AB  - Over the past few decades, epidemiology and natural history studies have led to
      improved understanding of human papillomavirus (HPV) infection and to promising
      prevention strategies. HPV infection is the cause of anogenital warts and
      cervical cancer, as well as a proportion of other anogenital and head and neck
      cancers. Data from clinical trials have resulted in recommendations that support
      the use of an HPV test in the context of cervical cancer screening and
      management. Prophylactic HPV vaccine trials have demonstrated high efficacy, and
      an HPV vaccine that prevents cervical cancer precursors, cervical cancer, and
      anogenital warts caused by HPV types 6, 11, 16, and 18 was licensed for use in
      girls and women aged 9-26 years by the US Food and Drug Administration (FDA) in
      June 2006. In this article, we review genital HPV for the clinician, with a
      primary focus on the prevalence of HPV infection in the United States.

PMID- 16886158
TI  - World Wide Web resources on antimicrobial resistance.
AB  - Advances of modern technology, including the development of the Internet and the
      World Wide Web, have given clinicians and researches the opportunity to have
      immediate access to continuously updated information in various scientific
      fields. We compiled a list of World Wide Web resources of data from surveillance
      studies on antimicrobial resistance that may be useful to practitioners-
      especially infectious diseases specialists--as well as to scientists with a
      research interest in the field of antimicrobial resistance.

PMID- 16886159
TI  - Tuberculin skin testing in patients with HIV infection: limited benefit of
      reduced cutoff values.
AB  - BACKGROUND: When determining eligibility for isoniazid preventive therapy of
      human immunodeficiency virus (HIV)-infected patients, the cutoff value of the
      tuberculin skin test (TST) is often reduced from an induration of 10 mm in
      diameter to one of 5 mm in diameter to compensate for loss of sensitivity. The
      effectiveness of this reduction depends on the underlying mechanism: a gradual
      decrease in skin test responsiveness with decreasing immunocompetence or an all
      or-nothing switch to complete anergy. No published studies have assessed this
      directly in patients with tuberculosis. METHODS: We performed a cross-sectional
      study of TST responses and HIV infection among patients with sputum smear
      positive pulmonary tuberculosis in 6 hospitals in Tanzania. Skin test anergy was
      defined as a TST reaction < or =2 mm in diameter. RESULTS: Of 991 patients with
      complete results, 451 (45.5%) had HIV infection. Anergy was observed in 111
      (24.6%) of 451 HIV-infected patients and 18 (3.3%) of 540 HIV-uninfected patients
      (P<.001). The reaction size distributions among nonanergic HIV-infected and
      uninfected patients showed a limited difference (mean diameter +/- standard
      deviation, 15.9 +/- 5.0 mm and 16.8 +/- 3.8 mm, respectively; P=.048). The
      sensitivity of the TST among HIV-uninfected patients was 91.1% at a cutoff value
      of 10 mm and 95.2% at a cutoff value of 5 mm. The sensitivity of the TST among
      HIV-infected patients was 64.3% at a cutoff value of 10 mm and 71.2% at a cutoff
      value of 5 mm; the sensitivity of the TST was 67.6% and 74.5%, respectively,
      after adjustment for tuberculosis-specific anergy. CONCLUSION: In subjects with
      tuberculosis disease and HIV infection, loss of TST sensitivity is predominantly
      attributable to anergy (i.e., an all-or-nothing phenomenon). The decrease in the
      proportion of false-negative TST results obtained by reducing the cutoff value
      from 10 mm to 5 mm is limited.

PMID- 16886160
TI  - Liver biopsy findings for HIV-infected patients with chronic hepatitis C and
      persistently normal levels of alanine aminotransferase.
AB  - BACKGROUND: Severe liver fibrosis is common in patients coinfected with human
      immunodeficiency virus (HIV) and hepatitis C virus (HCV) who have a high alanine
      aminotransferase (ALT) level. However, little is known about the frequency, liver
      biopsy findings, and significance of a persistently normal ALT level in
      coinfected patients. METHODS: We analyzed clinical data and histological findings
      for 256 patients coinfected with HIV and HCV, 24 (9.4%) of whom had an ALT level
      within the normal range on > or =2 separate occasions within a 6-month period.
      RESULTS: The proportion of patients demonstrating advanced stages of fibrosis (F3
      and F4) was 78 (33.7%) of 232 patients in the high ALT level group, compared with
      0 (0%) of 24 patients in the persistently normal ALT level group (P<.001). Among
      patients with persistently normal ALT levels, 23 (96%) had any grade of fibrosis,
      and 7 (29%) had stage F2 of fibrosis. No differences were found between both
      groups with respect to age, sex, HIV transmission category, Centers for Disease
      Control and Prevention clinical category, CD4+ cell count (both nadir and
      baseline values), type of antiretroviral therapy, years since onset of HCV
      infection, alcohol use, or HCV load. However, the proportion of patients infected
      with HCV genotype 3 was significantly higher among patients with high ALT levels
      than in patients with persistently normal ALT levels (61 [26.9%] of 232 patients
      vs. 1 [4.2%] of 24 patients; P=.04). CONCLUSIONS: Histological abnormalities are
      significantly milder in patients coinfected with HIV and HCV who have
      persistently normal ALT levels than those found in patients with high ALT levels.
      However, a subgroup of patients with persistently normal ALT levels may have
      significant cases of fibrosis. Liver biopsy may be recommendable in patients
      coinfected with HIV and HCV who have persistently normal ALT levels, to determine
      the extent of liver fibrosis and, consequently, to assess suitability for
      treatment.

PMID- 16886162
TI  - Comparative evaluation of adherence to antiretroviral therapy in sub-Saharan
      African native HIV-infected patients in France and Africa.
AB  - Patients with human immunodeficiency virus (HIV) infection who were native to sub
      Saharan Africa but lived in France were less adherent to antiretroviral therapy
      during a visit back to Africa, compared with their level of adherence in France.
      This was mainly related to self-perceived insufficient support from family
      members and/or fear of the consequences of disclosure of their HIV infection
      status to their family.

PMID- 16886161
TI  - Current concepts in the diagnosis and management of metabolic complications of
      HIV infection and its therapy.
AB  - Changes in fat distribution, dyslipidemia, disordered glucose metabolism, and
      lactic acidosis have emerged as significant challenges to the treatment of human
      immunodeficiency virus (HIV) infection. Over the past decade, numerous
      investigations have been conducted to better define these conditions, identify
      risk factors associated with their development, and test potential therapeutic
      interventions. The lack of standardized diagnostic criteria, as well as disparate
      study populations and research methods, have led to conflicting data regarding
      the diagnosis and treatment of metabolic and body shape disorders associated with
      HIV infection. On the basis of a review of the medical literature published
      and/or data presented before April 2006, we have prepared a guide to assist the
      clinician in the detection and management of these complications.

PMID- 16886164
TI  - Old polymyxins are back: is resistance close?

PMID- 16886163
TI  - Single-dose lopinavir-ritonavir acutely inhibits insulin-mediated glucose
      disposal in healthy volunteers.
AB  - Previously, we found that 4 weeks of treatment with lopinavir-ritonavir did not
      decrease insulin sensitivity but did increase adiponectin levels. In the present
      study, a single dose of lopinavir-ritonavir decreases insulin sensitivity but
      does not alter adiponectin levels. Insulin resistance from protease inhibitors
      may decrease with prolonged use; an increase in adiponectin levels may mediate
      this effect.

PMID- 16886165
TI  - First case of cutaneous reconstitution inflammatory syndrome associated with HIV
      infection and leishmaniasis.

PMID- 16886166
TI  - Is Candida kefyr an emerging pathogen in patients with oncohematological
      diseases?

PMID- 16886167
TI  - Prudence and optimal prevention for health risks.
AB  - Empirical evidence suggests the existence of a positive relationship between fear
      of sickness (FS) - as measured by the level of future utility lost when sickness
      occurs - and the level of effort to prevent the occurrence of sickness. By
      looking theoretically at this issue, we develop new results on the determinants
      of optimal prevention for health risks. In particular, we show that a sufficient
      condition to pursue more prevention for an individual with a higher FS than
      another is to have lower prudence in Kimball's (1990) sense, whatever the
      distribution of risk. These findings reinforce the role of prudence as a main
      determinant of the optimal level of prevention.

PMID- 16886168
TI  - Redox-sensitive modulation of CD45 expression in pancreatic acinar cells during
      acute pancreatitis.
AB  - CD45, a transmembrane protein tyrosine phosphatase required for signal
      transduction in leukocytes, has recently been found in pancreatic acinar cells.
      We have investigated the relationship between kinetic expression of CD45 on
      acinar cells during acute pancreatitis (AP) and the ability of these cells to
      produce tumour necrosis factor-alpha (TNF-alpha) through mechanisms sensitive to
      the cellular redox state. Flow cytometric analysis showed a significant decrease
      in the constitutive expression of CD45 in acinar cells from six hours onwards
      after inducing AP by bile-pancreatic duct obstruction (BPDO) in parallel with a
      significant increase in acinar TNF-alpha production. Changes in protein
      expression on the acinar cell surface preceded CD45 mRNA down-regulation, which
      was not found until 12 hours after BPDO. N-Acetylcysteine treatment delayed and
      reduced the down-regulation of CD45 expression induced by AP and prevented acinar
      cells from producing TNF-alpha. Our results show that CD45 expression is down
      regulated in acinar cells during acute pancreatitis by redox-sensitive
      mechanisms, and they support the notion that CD45 negatively controls the
      production of cytokines in pancreatic acinar cells.

PMID- 16886171
TI  - Genetics and evidence for an esterase-associated mechanism of resistance to
      indoxacarb in a field population of diamondback moth (Lepidoptera: Plutellidae).
AB  - Bioassays (at generation G2) with a newly collected field population (designated
      CH3) of Plutella xylostella L. from farmers' fields in the Cameron Highlands,
      Malaysia, indicated resistance ratios of 813-, 79-, 171-, 498- and 1285-fold for
      indoxacarb, fipronil, spinosad, deltamethrin and Bacillus thuringiensis toxin
      Cry1Ac respectively compared with a laboratory susceptible population (Lab-UK).
      At G2 the field-derived population was divided into two subpopulations: one was
      selected (G2 to G7) with indoxacarb (indoxa-SEL), while the second was left
      unselected (UNSEL). A significant reduction in the resistance ratio for each
      compound was observed in UNSEL at G8. For indoxa-SEL, bioassays at G8 found that
      selection with indoxacarb gave a resistance ratio of 2594 compared with Lab-UK
      and of 90 compared with UNSEL. The toxicity of fipronil, spinosad and
      deltamethrin was not significantly different in indoxa-SEL at G8 compared with G2
      but was significantly greater than UNSEL at G8. The toxicity of Cry1Ac was
      significantly reduced in indoxa-SEL at G8 compared with G2 but was also
      significantly greater than UNSEL at G8. This suggests that indoxacarb selection
      maintained resistance to these compounds in the indoxa-SEL population. Synergist
      studies indicated that resistance to indoxacarb in indoxa-SEL was esterase
      associated. Logit regression analysis of F1 reciprocal crosses between indoxa-SEL
      and Lab-UK indicated that resistance to indoxacarb was inherited as an autosomal,
      incompletely recessive (D(LC) = 0.35) trait. Tests of monogenic inheritance
      suggested that resistance to indoxacarb was controlled by a single locus.

PMID- 16886170
TI  - Evaluation of the bioavailability of the herbicide prosulfocarb through
      adsorption on soils and model soil colloids, and through a simple bioassay.
AB  - Adsorption isotherms of prosulfocarb were determined on soils with different
      physicochemical properties. The extent of adsorption increased with the organic
      carbon content, but the results also suggested the involvement of some inorganic
      soil surfaces. In order better to understand the role of each soil surface,
      adsorption-desorption isotherms were determined on model soil colloids consisting
      of a soil humic acid, a montmorillonite, a synthetic aluminium hydroxide and
      their associations. The highest adsorption was observed on the humic acid, but it
      was also confirmed that the montmorillonite interacted with prosulfocarb. In
      contrast, the aluminium hydroxide was not active and its association with
      montmorillonite provoked a decrease in adsorption compared with montmorillonite
      alone. Except for humic acid, the highest adsorption took place on the ternary
      association montmorillonite-aluminium hydroxide-humic acid. On each surface
      tested, the adsorption was largely reversible and decreased at increasing pH. The
      herbicidal activity of prosulfocarb was tested by the determination of the
      germination and growth of a typical weed, Lolium multiflorum Lam, in contact with
      prosulfocarb solutions at different concentrations. The herbicide did not prevent
      the germination of the seeds but inhibited the growth of the roots and leaves.
      The same test was performed in the presence of the ternary system to evaluate the
      influence of adsorption on the plant bioavailability. It was concluded that the
      presence of an adsorptive surface reduced the herbicidal activity and that the
      simple bioassay proposed could be useful in predicting the extent of adsorption
      in a given soil.

PMID- 16886174
TI  - Behavioural response of Colorado potato beetle (Leptinotarsa decemlineata) larvae
      to selected plant extracts.
AB  - Potato leaves were treated with 2, 20 or 200 g kg(-1) solutions of extracts of
      five plant species collected in Turkey, and then exposed to larvae of Colorado
      potato beetle, Leptinotarsa decemlineata (Say). During the first 24 h of
      exposure, leaf consumption was not affected by 2 g kg(-1) extracts, whereas
      significantly more leaf tissue remained on leaves treated with 20 g kg(-1)
      extracts of Arctium lappa L., Bifora radians M Bieb, Humulus lupulus L. or
      Xanthium strumarium L. than on untreated control leaves. Feeding was not affected
      by the 20 g kg(-1) extract of Verbascum songaricum Schrenk ex Fisch & Mey.
      Extracts of all species at 200 g kg(-1) reduced larval feeding, with H. lupulus
      and X. strumarium providing the greatest protection. Observations of larval
      behaviour over the first 15 min of exposure to these extracts revealed that the
      interaction of beetles with leaf tissue was significantly affected by plant
      extracts. Feeding frequency was not affected by 2 g kg(-1) extracts but was
      reduced by all higher concentrations. Feeding was inhibited completely by 20 g
      kg(-1) of H. lupulus extract and reduced significantly compared with the controls
      by all other extracts. Suppression of feeding was caused by all extracts at 200 g
      kg(-1), with V. songaricum providing 91% reduction in feeding duration. Rejection
      behaviour, in which larvae did not return to the leaf after their interaction
      with it, was rare on 2 g kg(-1) extracts but seen in over 60% of larvae on 20 g
      kg(-1) extracts and over 80% on 200 g kg(-1) extracts. The present results
      demonstrate that these extracts have significant ability to protect potato leaves
      for up to 24 h by prevention of feeding behaviour by L. decemlineata. Further
      studies are needed to determine the potential of these plant extracts, or their
      active components, for use in biologically based pest management strategies.

PMID- 16886175
TI  - Comprehensive long-term follow-up programs for pediatric cancer survivors.
AB  - BACKGROUND: The objective of this study was to provide a detailed description of
      comprehensive long-term follow-up (LTFU) programs for pediatric cancer survivors.
      METHODS: Program directors from 24 comprehensive LTFU programs in the U.S. and
      Canada completed a 6-page survey that provided details in 5 categories:
      description of the program, perceived benefits and strengths of the program,
      barriers to the development and use of the program, methods to improve the
      program, and an ideal model of care for pediatric cancer survivors. RESULTS:
      Participants identified the following primary benefits to health care delivered
      to survivors through LTFU programs: health care delivered by clinicians familiar
      with long-term risks of survivors, provision of risk-based screening and
      surveillance for late effects, and targeted education for risk reduction and
      healthy lifestyles. Key barriers to the functioning of LTFU programs included
      system-driven and patient/survivor-driven factors. System-driven factors included
      inadequate resources and finances to sustain programs, low institutional
      commitment toward the provision of survivorship care, lack of capacity to care
      for the growing population of survivors, and difficulties with ongoing
      communication with community physicians. Survivor-driven barriers included lack
      of interest and lack of awareness of cancer-related risks. CONCLUSIONS: This
      report describes the frequency, content, and setting of follow-up care delivered
      by pediatric comprehensive LTFU programs. Critical challenges as survivorship
      care evolves will include integrating a structured process of program evaluation
      and building capacity for care.

PMID- 16886176
TI  - Caspase-8 levels correlate with the expression of signal transducer and activator
      of transcription 1 in high-grade but not lower grade neuroblastoma.
AB  - BACKGROUND: Previous studies in advanced-stage neuroblastoma (NB) have shown a
      link between the silencing of caspase-8 and methylation of a regulatory region at
      the boundary between caspase-8 exon 3 and intron 3. However, a number of recent
      studies from NB cell lines have shown that the transcriptional regulation of
      caspase-8 may reside with interferon gamma-sensitive promoters through the action
      of transcription factors, such as signal transducer and activator of
      transcription 1 (STAT-1). In this study, the authors tested the hypothesis that
      there is a correlation between caspase-8 and STAT-1 protein expression levels
      that may be linked to methylation of the regulatory elements of either of these
      genes. METHODS: Thirty clinical tumor samples of all stages, including 13 samples
      from patients with Stage 4 disease, were analyzed by quantitative immunoblotting
      for caspase-8 and STAT-1. The DNA methylation status of putative caspase-8 and
      STAT-1 regulatory elements were determined by bisulfite-modified sequencing
      analysis. RESULTS: A significant correlation was observed between caspase-8 and
      STAT-1 protein levels in Stage 4 NB samples but not in lower stage NB samples.
      Caspase-8 and STAT-1 protein levels varied widely across all stages of NB and did
      not correlate with methylation of these genes. CONCLUSIONS: A strong correlation
      was observed between STAT-1 levels and caspase-8 levels in clinical Stage 4 NB.
      This suggests that STAT-1 or similar transcription factors, and not methylation,
      may play a role in controlling caspase-8 levels in this illness. No evidence of
      such a correlation between caspase-8 and STAT-1 levels was observed in lower
      clinical stages, suggesting that mechanisms controlling caspase-8 expression in
      NB vary with clinical stage.

PMID- 16886177
TI  - A data base for partition of volatile organic compounds and drugs from
      blood/plasma/serum to brain, and an LFER analysis of the data.
AB  - Literature values of the in vivo distribution (BB) of drugs from blood, plasma,
      or serum to rat brain have been assembled for 207 compounds (233 data points). We
      find that data on in vivo distribution from blood, plasma, and serum to rat brain
      can all be combined. Application of our general linear free energy relationship
      (LFER) to the 207 compounds yields an equation in log BB, with R2=0.75 and a
      standard deviation, SD, of 0.33 log units. An equation for a training set
      predicts the test set of data with a standard deviation of 0.31 log units. We
      further find that the in vivo data cannot simply be combined with in vitro data
      on volatile organic and inorganic compounds, because there is a systematic
      difference between the two sets of data. Use of an indicator variable allows the
      two sets to be combined, leading to a LFER equation for 302 compounds (328 data
      points) with R2=0.75 and SD=0.30 log units. A training equation was then used to
      predict a test set with SD=0.25 log units.

PMID- 16886178
TI  - Polyion complex micelles composed of all-trans retinoic acid and poly (ethylene
      glycol)-grafted-chitosan.
AB  - The goal of this study is to develop novel types of polyion complex micelles for
      the drug delivery to brain tumor. Methoxy poly(ethylene glycol) (mPEG)-grafted
      chitosan (CP) was synthesized in order to make polymeric micelles encapsulating
      all-trans retinoic acid (ATRA) based on polyion complex formation. Polyion
      complex micelles were found to have spherical shapes with sizes of about 50
      approximately 200 nm. The loading efficiency of micelle was higher than 80% (w/w)
      for all formulations. 1H nuclear magnetic resonance (NMR) spectra confirmed the
      formation of polymeric micelles. The CP graft copolymer and ATRA have
      distinguishing peaks in their 1H NMR spectra. The specific peaks of ATRA
      disappeared in D2O or DMSO while it appeared at mixtures of D2O/DMSO, indicating
      that ATRA and chitosan formed ion complex inner-core. In the cell cytotoxicity
      study using U87MG cells in vitro, polyion complex micelles showed similar
      cytotoxicity to that of free ATRA. A migration test was performed to investigate
      the inhibition of tumor cell invasion in vitro. The results suggested that the
      polyion complex micelles was more effective at inhibiting tumor cell migration
      than free ATRA.

PMID- 16886179
TI  - Parental and perinatal factors influencing the development of handedness in
      captive chimpanzees.
AB  - It has been proposed that human right handedness is determined by genetic factors
      associated with the emergence of language, whereas non-human primate handedness
      is determined by random, non-genetic factors. These different mechanisms account
      for differences in the distribution of handedness between human and non-human
      primates. Here we report evidence that genetic factors play a role in the
      determination of handedness in chimpanzees. We further report that differential
      rearing has no influence on the expression of handedness in related individuals.
      Contrary to many theories of the origin of handedness, these results indicate
      that genetic factors have a significant influence on handedness in chimpanzees.

PMID- 16886180
TI  - The manifestation of infant hand-use preferences when reaching for objects during
      the seven--to thirteen-month age period.
AB  - Handedness is an aspect of hemispheric specialization whose pattern of expression
      may signal an unusual specialization that in turn, may underlie several
      developmental psychopathologies. It is generally believed that infant handedness
      is neither stable nor reliable and hence, cannot be used as an early marker of
      potential developmental abnormality of hemispheric specialization. We show that
      infant hand-use preferences for apprehending objects can be reliably assessed and
      may be relatively stable throughout the 7-13 month age period. However, the
      results also demonstrate that identifying infant handedness requires assessment
      using very large sample sizes with multiple assessment periods because it is
      likely that there may be many more than three patterns in the development of
      handedness during infancy.

PMID- 16886181
TI  - Quantitative assessment of right and left reaching movements in infants: a
      longitudinal study from 6 to 36 months.
AB  - This longitudinal study aimed to explore the early presence and developmental
      pattern of laterality in reaching kinematics and its relationship to side use. In
      order to do so, 3-D kinematic measurements as well as 2-D video recordings of
      right-left reaching movements were successively carried out for 17 infants at the
      ages of 6, 9, 12, and 36 months. Additional investigations of hand preference
      were made at 36 months. As four infants were prematurely born, their outcomes
      were compared to those of the fullterm participants. While most of the infants in
      the early ages showed a rather inconsistent preference in terms of frequency and
      distributions of right-left side use, the analyses of reaching kinematics
      revealed a more consistent pattern of fewer movements units (MUs) and straighter
      right-sided reaching for the majority of infants at all tested ages. However,
      reaching kinematics from the preterm infants were generally more variable and
      less side consistent. It is proposed that the development of human handedness
      originates from an early right arm rather than hand preference in that
      representations of asymmetry in bilateral projections (involved in arm movements)
      developmentally precede contralateral projections (involved in refined
      hand/finger movements).

PMID- 16886182
TI  - Grid-based molecular modeling for pharmaceutical salt screening: Case example of
      3,4,6,7,8,9-hexahydro-2H-pyrimido (1,2-a) pyrimidinium acetate.
AB  - The development of modeling capabilities for improving the efficiency with which
      solid-state pharmaceutical products can be developed is a key strategic goal for
      the pharmaceutical research and development sector. In this context, an important
      topic is the salt-selection process associated with drug-product formulation
      development. In this study, a systematic (grid-based) search method is used to
      predict the host/counter-ion binding for a simple but representative organic salt
      (i.e., a type I organic acid salt former having a single ionisable group):
      3,4,6,7,8,9-hexahydro-2H-pyrimido (1,2-a) pyrimidinium acetate ([H2hpp][O2CCH3]).
      The relative disposition of the two ionic moieties in the asymmetric unit and,
      from this, the crystal packing in this compound are also predicted using the
      systematic grid-based search method linked to the known crystallographic unit
      cell dimensions. The overall strategy adopted encompasses three main steps:
      molecular pair search; optimization and clustering; and crystal lattice search
      and optimization. The predicted results, using this method, reveal a good
      agreement between the calculated crystal structure and that obtained from the
      Cambridge Crystallographic Structure Database (CCSD), indicating that the
      approach offers considerable promise for application as part of an integrated
      strategy for pharmaceutical salt selection.

PMID- 16886183
TI  - The evolutionary psychology of left and right: costs and benefits of
      lateralization.
AB  - Why do the left and right sides of the vertebrate brain play different functions?
      Having a lateralized brain, in which each hemisphere carries out different
      functions, is ubiquitous among vertebrates. The different specialization of the
      left and right side of the brain may increase brain efficiency--and some evidence
      for that is reported here. However, lateral biases due to brain lateralization
      (such as preferences in the use of a limb or, in animals with laterally placed
      eyes, of a visual hemifield) usually occur at the population level, with most
      individuals showing similar direction of bias. Individual brain efficiency does
      not require the alignment of lateralization in the population. Why then are not
      left--and right-type individuals equally common? Not only humans, but most
      vertebrates show a similar pattern. For instance, in the paper I report evidence
      that most toads, chickens, and fish react faster when a predator approaches from
      the left. I argue that invoking individual brain efficiency (lateralization may
      increase fitness), evolutionary chance or direct genetic mechanisms cannot
      explain this widespread pattern. Instead, using concepts from mathematical theory
      of games, I show that alignment of lateralization at the population level may
      arise as an "evolutionarily stable strategy" when individually asymmetrical
      organisms must coordinate their behavior with that of other asymmetrical
      organisms. Thus, the population structure of lateralization may result from genes
      specifying the direction of asymmetries which have been selected under "social"
      pressures.

PMID- 16886184
TI  - Plasticity in the development of handedness: evidence from normal development and
      early asymmetric brain injury.
AB  - Previous research revealed that shifting patterns of hand preference in the first
      year of life are linked to infants' sensory-motor experiences as they learn to
      sit, creep, and walk. In this report, we examine whether new and different forms
      of locomotion and sensory-motor experiences similarly contribute to alter
      patterns of hand preference in early development. We examined the cases of three
      infants with unique developmental histories. Two infants adopted distinctive
      forms of locomotion in lieu of typical hands-and-knees crawling. One infant
      scooted using both hands and legs in a coupled fashion, while the other infant
      performed an asymmetrical, left-biased belly-crawl using only one arm to drag his
      body. The third infant suffered damage to his left-brain hemisphere shortly after
      birth and received intense physical therapy to his right arm as a result of it.
      We followed all three infants on a weekly basis and tracked changes in their
      reaching behavior, mode of locomotion, and postural achievements. The two infants
      with unique locomotor patterns displayed changes in hand preference that
      reciprocated the arm patterns that they used during locomotion. The infant who
      coupled his body for scooting began to reach bimanually, while the infant who
      adopted the left-biased belly-crawl developed a strong unimanual, right-hand,
      preference. The infant with left-hemisphere damage initially displayed a right
      hand preference, then a temporary decline in preferred hand use as he began to
      cruise and walk, and ultimately resumed a right-hand preference in the 2nd year
      of life. This data is consistent with previous work showing that the development
      of hand preference in the 1st year of life is highly malleable and sensitive to a
      variety of new sensory-motor experiences.

PMID- 16886185
TI  - Agenesis of the corpus callosum and the establishment of handedness.
AB  - The goal of this study was to check whether an isolated agenesis of the corpus
      callosum, detected in utero with ultrasound recording, would impair the early
      development of unimanual and bimanual handedness. Twelve infants with isolated
      agenesis of the corpus callosum, either total (TACC) or partial (PACC) were
      tested for handedness at the end of their first year, and were compared to
      infants with typical development (TD), matched for age and sex. A majority of
      infants showed right-handedness at the unimanual grasping tasks, with no
      significant difference between the TD and ACC groups. When the object was
      presented to the left, the TACC infants were more likely to grasp the object with
      their right hand (with or without the left hand) than both the TD and the PACC
      infants who used mostly the ipsilateral left hand. The only significant
      difference between TD and ACC infants concerned bimanual coordination, as less
      ACC infants (especially TACC) succeeded at the bimanual task, compared with TD
      infants. In addition, the strategy of the former tended to be less right-handed
      than that of the latter. Our results confirm the role of the CC in bimanual
      coordination, indicating that the early emergence of bimanual coordination and,
      if confirmed, bimanual handedness, are likely to be delayed in the absence of
      corpus callosum, especially if agenesis is total. They do not support the idea
      that the CC is necessary for the early onset of handedness.

PMID- 16886186
TI  - Laterality in persons with intellectual disability II. Hand, foot, ear, and eye
      laterality in persons with Trisomy 21 and Williams-Beuren syndrome.
AB  - Laterality (hand, foot, ear, and eye) was assessed in participants with Trisomy
      21 (62) and Williams-Beuren syndrome (WBS) (39). Handedness was also assessed in
      a card reaching task. The comparison group included 184 typically developing
      persons. Two independent age sub-groups were formed: 7 to 10 years old and 11 to
      34 years old. We confirmed previous data: individuals with T21 were more
      frequently left- or mixed-handed than typically developing persons; individuals
      with WBS had intermediate scores. The two groups with genetic disorders had less
      right foot preference. Manual and foot inconsistencies characterized both groups
      with genetic disorders. Cross hand-foot preference was lower in the typically
      developing group. Differences in IQ levels did not correlate with differences in
      laterality scores. Overall laterality profiles were not the same in the two
      groups with genetic disorders: the greatest differences were observed between
      typically developing persons and persons with Trisomy 21.

PMID- 16886187
TI  - De Novo synthesis of CREB in a presynaptic neuron is required for synaptic
      enhancement involved in memory consolidation.
AB  - Interaction between the activator type of cyclic AMP response element binding
      protein (CREB1) and the repressor type (CREB2) results in determining the
      emergence of long-lasting synaptic enhancement involved in memory consolidation.
      However, we still do not know whether the constitutively expressed forms of CREB
      are enough or the newly synthesized forms are required for the synaptic
      enhancement. In addition, if the newly synthesized forms are needed, we must
      determine the time for translation of CREB from its mRNA. We applied the methods
      of RNA interference and real-time polymerase chain reaction (PCR) to CREB in the
      cerebral giant cells of Lymnaea. The cerebral giant cells play an important role
      in associative learning and employ a CREB cascade for the synaptic enhancement to
      neurons such as the B1 motoneurons. We injected the small interfering RNA (siRNA)
      of CREB1 or CREB2 into the cerebral giant cells and examined the changes in
      amplitude of excitatory postsynaptic potential (EPSP) recorded in the B1
      motoneurons. The changes in the amounts of CREB1 and CREB2 mRNAs were also
      examined in the cerebral giant cells. The EPSP amplitude was suppressed 15 min
      after injection of CREB1 siRNA, whereas that was augmented 60 min after injection
      of CREB2 siRNA. In the latter case, the decrease in the amount of CREB2 mRNA was
      confirmed by real-time PCR. Our results showed that the de novo synthesized forms
      of CREB are required within tens of minutes for the synaptic enhancement in
      memory consolidation.

PMID- 16886188
TI  - Insulin promotes diacylglycerol kinase activation by different mechanisms in rat
      cerebral cortex synaptosomes.
AB  - The mechanism by which insulin increases diacylglycerol kinase (DAGK) activity
      has been studied in cerebral cortex (CC) synaptosomes from adult (3-4 months of
      age) rats. The purpose of this study was to identify the role of phospholipases C
      and D (PLC and PLD) in DAGK activation by insulin. Neomycin, an inhibitor of PLC
      phosphatidylinositol-bisphosphate (PIP2) specific; ethanol, an inhibitor of
      phosphatidic acid (PA) formation by the promotion of a transphosphatidyl reaction
      of phosphatidylcholine phospholipase D (PC-PLD); and DL propranolol, an inhibitor
      of phosphatidate phosphohydrolase (PAP), were used in this study. Insulin (0.1
      microM) shielded an increase in PA synthesis by [32P] incorporation using [gamma
      32P]ATP as substrate and endogenous diacylglycerol (DAG) as co-substrate. This
      activated synthesis was strongly inhibited either by ethanol or DL propranolol.
      Pulse chase experiments also showed a PIP2-PLC activation within 1 min exposure
      to insulin. When exogenous unsaturated 18:0-20:4 DAG was present, insulin
      increased PA synthesis significantly. However, this stimulatory effect was not
      observed in the presence of exogenous saturated (di-16:0). In the presence of
      R59022, a selective DAGK inhibitor, insulin exerted no stimulatory effect on
      [32P]PA formation, suggesting a strong relationship between increased PA
      formation by insulin and DAGK activity. These data indicate that the increased
      synthesis of PA by insulin could be mediated by the activation of both a PC-PLD
      pathway to provide DAG and a direct DAGK activation that is associated to the use
      of 18:0-20:4 DAG species. PIP2-PLC activation may contribute at least partly to
      the insulin effect on DAGK activity.

PMID- 16886189
TI  - Enhancement of transdermal testosterone delivery by supersaturation.
AB  - The objective was to evaluate supersaturation in the development of a spray
      formulation for transdermal testosterone delivery. The method of cosolvents was
      used to prepare supersaturated testosterone vehicles, the stability of which was
      evaluated. Drug delivery from selected formulations, and from a simpler spray,
      was then assessed across hairless rat skin in vitro. Supersaturated drug
      solutions were formed either by rapidly adding water to a drug-saturated 4:1:1
      ethanol/propylene glycol (PG)/water mixture, or by maintaining the proportion of
      water constant, while varying the relative amounts of ethanol and PG. In the
      former case, only small degrees of saturation (DS) could be maintained, and drug
      flux was increased only modestly. The latter approach produced more stable
      formulations with DS = 2 to 4. A 1:1 ethanol/PG spray containing saturated
      testosterone delivered drug as efficiently as a supersaturated vehicle with DS =
      2.5. Preparation of supersaturated testosterone formulations is possible,
      therefore, but significant amounts of water lead to rapid drug crystallization.
      As percentage PG increases, better stability results, but the practicality of
      using such vehicles in sprays and aerosols may be questioned. Nevertheless, a
      simple 1:1 ethanol/PG spray apparently induces supersaturation in situ, and
      further work to optimize the approach is warranted.

PMID- 16886190
TI  - Lateral preferences in children with intellectual deficiency of idiopathic
      origin.
AB  - The goal of this study was to evaluate lateral preferences in a population of
      children with intellectual deficiency of idiopathic origin, compared with those
      of typically developing (TD) children. Two groups of children with mild or
      moderate intellectual deficiency were observed. Handedness (using a 10-item test
      and Bishop's card-reaching task), eyedness and footedness were studied. The
      younger group consisted of sixteen 10- to 11-year olds; the older group comprised
      fourteen 12- to 14-year olds. A control group of fifteen TD children was matched
      for age with the younger group of intellectually deficient (ID) children. The
      results show that the occurrence of left-handedness is not higher in children
      with ID of unknown origin than in age-matched TD children. However, we observed a
      marginally reduced tendency toward right-handedness in ID than in TD children:
      more mixed-handers among ID than TD children; test-retest consistency of hand
      preference significantly lower in the 10- to 11-year-old ID children than in the
      age-matched TD children; greater tendency of ID children to use their
      nonpreferred left hand when the card was presented to the left, as compared with
      TD children. Left-eyedness and crossed hand-eye preference were also more
      frequent in ID than in age-matched TD children. No age-related difference in
      laterality was found in ID children. These results partially support other
      studies indicating that less rightward asymmetry is associated with intellectual
      deficiency in children.

PMID- 16886191
TI  - Pharmacokinetics of chlorzoxazone in rats with diabetes: Induction of CYP2E1 on 6
      hydroxychlorzoxazone formation.
AB  - Pharmacokinetic parameters of chlorzoxazone (CZX) and its main metabolite, 6
      hydroxychlorzoxazone (OH-CZX), were compared after intravenous (20 mg/kg) and
      oral (50 mg/kg) administration of CZX in rat model of diabetes induced by alloxan
      (DMIA) or streptozotocin (DMIS), and their respective control rats. In both rat
      models of diabetes, the expression and mRNA level of CYP2E1 increased, and CZX
      was metabolized to OH-CZX via CYP2E1 in rats. Hence, it could be expected that
      formation of OH-CZX increased in both rat models of diabetes. As expected, after
      intravenous (80.5% and 74.4% increase in rat models of DMIA and DMIS,
      respectively) and oral (55.6% and 70.5% increase, respectively) administration of
      CZX, the AUC of OH-CZX was significantly greater than their respective control
      rats. Since, CZX is an intermediate hepatic extraction ratio drug, the greater
      AUC values of OH-CZX (the significantly faster CL(NR) of CZX) in both rat models
      of diabetes could be supported by significantly faster CL(int) for the formation
      of OH-CZX (75.9% and 129% increase for rat models of DMIA and DMIS, respectively)
      and significantly greater free fractions of CZX in plasma (51.9% and 58.9%
      increase, respectively). Also it was reported that hepatic blood flow rate was
      faster in male Wister rat model of DMIS.

PMID- 16886192
TI  - Solubilization and dissolution of tamoxifen-hydroxybutenyl cyclodextrin
      complexes.
AB  - The solubility and dissolution of tamoxifen base and tamoxifen citrate with and
      without hydroxybutenyl-beta-cyclodextrin (HBenBCD) in aqueous and organic media
      were examined. The solubility of tamoxifen was greatly enhanced by complexation
      with HBenBCD; pH of the medium, and choice of buffer significantly impacted the
      amount of drug that could be solubilized. Different tamoxifen:HBenBCD
      formulations were prepared, including liquid fill capsule formulations, and their
      dissolution profiles were obtained. These dissolution studies demonstrated that
      enhanced solubilization of tamoxifen with HBenBCD was effective across a wide
      variety of formulation options. By complexation of tamoxifen base with HBenBCD,
      it was possible to obtain solubility and dissolution profiles for tamoxifen base
      that were essentially identical to that of tamoxifen citrate.

PMID- 16886193
TI  - Flurbiprofen loaded biodegradable nanoparticles for ophtalmic administration.
AB  - Poly(lactic/glycolic) acid nanoparticles incorporating flurbiprofen (FB) were
      prepared by the solvent displacement technique using poloxamer 188 as a
      stabilizer to improve the availability of the drug for the prevention of the
      inflammation caused by ocular surgery. A 2(3) + star design was applied to
      investigate the influence of several factors such as the pH of the aqueous phase,
      the initial concentration of the stabilizer, and the drug used to prepare the
      nanoparticles (NPs) on the physicochemical properties (particle size analysis,
      zeta potential, and drug loading efficiency) of the colloidal system. The best
      formulations were those prepared at pH 3.5 with a concentration of 1.5 mg/mL of
      FB and 10 or 20 mg/mL of poloxamer 188. These formulations showed an appropriate
      average size for ophthalmic administration (232.8 and 277.6 nm, respectively) and
      a good yield of entrapment efficiency (94.60% and 93.55%, respectively). The
      release behavior of FB from the developed NPs was complete and exhibited a
      biphasic pattern. Formulations did not show toxicity on ocular tissues. In vivo
      anti-inflammatory efficacy was assessed in the rabbit eye after topical
      instillation of sodium arachidonate (SA). A higher decrease of the SA-induced
      inflammation was obtained for the NP formulations.

PMID- 16886194
TI  - Involvement of intracellular Ca2+ dynamics in cytoprotective action by amino
      acids and cytotoxicity by sodium laurate, an absorption enhancer.
AB  - In our previous studies, taurine (Tau) and L-glutamine protected intestinal
      epithelial cells from local toxicity caused by sodium laurate (C12), an
      absorption enhancer, while maintaining sufficient absorption-enhancing effect of
      C12, and it was suggested that one of the mechanisms behind cytoprotection by
      amino acids was to prevent intracellular Ca2+ concentration ([Ca2+]i) from
      increasing. In the present study, we focused on the elucidation of mechanisms by
      which C12 increases [Ca2+]i and by which amino acids suppress [Ca2+]i by
      utilizing Caco-2 cells. Removal of extracellular Ca2+ remarkably suppressed the
      increase of [Ca2+]i by C12. Compound 48/80, an inhibitor of phospholipase C, and
      verapamil, a Ca2+ channel inhibitor, also significantly prevented [Ca2+]i
      elevation. These results indicate that C12 augmented [Ca2+]i due to (a) influx of
      extracellular Ca2+ through Ca2+ channel, (b) release of Ca2+ from the endoplasmic
      reticulum. Cytoprotective action by amino acids was significantly attenuated by
      orthovanadate, an inhibitor of plasma membrane Ca2+-ATPase (PMCA), suggesting
      that amino acids activate PMCA to enhance the efflux of intracellular Ca2+.
      Furthermore, Tau enhanced the mitochondrial uptake of Ca2+, which could
      contribute to the decrease in [Ca2+]i. These results clearly show that amino
      acids protect intestinal epithelial cells from being damaged by modulating
      intracellular Ca2+ dynamics.

PMID- 16886195
TI  - Effect of pressure on molecular and ionic motions in ultraviscous acetaminophen
      aspirin mixture.
AB  - Effect of pressure and temperature on molecular motions and dc conductivity in
      ultraviscous, 50 wt% acetaminophen-aspirin melt has been studied by dielectric
      relaxation spectroscopy. The spectra obtained over the pressure range, 5-300 MPa
      and temperature range, 295-320 K show a distribution of relaxation times greater
      than found in pure acetaminophen. The equilibrium dielectric permittivity and
      relaxation time, tau, of the melt increase with increase in pressure and decrease
      in temperature and the dc conductivity, sigma(dc), decreases. The pressure and
      temperature variation of the limiting high frequency permittivity shows
      significant contribution from infrared polarization. The volumes of activation
      for sigma(dc) and tau vary with both the pressure and temperature, indicating
      that there is also a structural effect that determine sigma(dc). This effect
      would add a non-linear term to the Debye-Stokes-Einstein equation for variation
      of sigma(dc) with tau. The ultraviscous liquid remains stable with time, and with
      change in temperature and pressure, suggesting that a more stable glassy state of
      a pharmaceutical may be obtained by mixing a second component.

PMID- 16886196
TI  - Simultaneous quantification of carbamazepine crystal forms in ternary mixtures
      (I, III, and IV) by diffuse reflectance FTIR spectroscopy (DRIFTS) and
      multivariate calibration.
AB  - Diffuse reflectance FTIR spectroscopy (DRIFTS) coupled with modern multivariate
      calibration methods, namely artificial neural networks (ANNs) in two versions
      (ANN-raw and ANN-pca), support vector machines (SVMs), lazy learning (LL) and
      partial least squares (PLS) regression, is used in this study for the
      quantification of carbamazepine crystal forms in ternary powder mixtures (I, III,
      and IV). Two spectral regions (675-1180 and 3400-3600/cm) were selected and the
      data were partitioned into training and test subsets applying the Kennard-Stone
      design. It was found that all the selected algorithms perform better than the PLS
      regression (root mean squared error of prediction (RMSEP) from 3.0% to 8.2%). ANN
      raw, trained on uncompressed spectral data, shows best predictive performance
      (RMSEP < 2.25%) but longest computation (up to 10 min). Principal component
      analysis (PCA) compression of the input spectral data accelerates significantly
      the computation (<16 s) at a relatively low cost in precision (RMSEP < 3.24%).
      The LL algorithm shows excellent performance in the 3400-3600/cm range (RMSEP <
      1.6%), but in the 675-1180/cm range it shows strong dependence on data set
      structure (RMSEP between 1.6% and 8.9%). SVMs perform comparably well with ANNs
      (RMSEP < 3.1%), not showing the long computation time of ANNs (<1 s) and
      therefore may provide an attractive alternative to ANNs.

PMID- 16886197
TI  - A new solution for a chronic problem; aqueous enteric coating.
AB  - In this research, we have reconsidered the current enteric coating techniques and
      offered a new solution using both theoretical and practical approaches. This
      approach is based on the fact that salt formation can solubilize the pH-sensitive
      polymers in water. However, having applied the polymer solution onto the dosage
      form's surface, the polymer should be converted to the nonionized form for
      delayed release action. Ammonium hydrogen carbonate (AHC) is used as a buffering
      agent with dual actions of salting in and desalting the polymer. Following the
      application of the coating medium onto the dosage form's surface and drying, AHC
      dissociate completely to ammonia, carbon dioxide, and water converting the
      polymer to its nonionized form. FT-IR studies on free film samples further
      confirmed the proposed mechanism. A range of pH-sensitive polymers and other
      ingredients in water have been successfully applied at the surface of a model ASA
      tablets, using pan coating technique. According to the SEM observation, the
      coating layer is very dense and rigid, despite the fact that, the coated amount
      of the polymers is quit small. The enteric tablets maintain their shapes in acid
      medium and passed the USP dissolution test for DR ASA tablets.

PMID- 16886198
TI  - Ultra-fast absorption of amorphous pure drug aerosols via deep lung inhalation.
AB  - A deficiency of most current drug products for treatment of acute conditions is
      slow onset of action. A promising means of accelerating drug action is through
      rapid systemic drug administration via deep lung inhalation. The speed of
      pulmonary drug absorption depends on the site of aerosol deposition within the
      lung and the dissolution rate and drug content of the deposited particles.
      Alveolar delivery of fast-dissolving, pure drug particles should in theory enable
      very rapid absorption. We have previously shown that heating of thin drug films
      generates vapor-phase drug that subsequently cools and condenses into pure drug
      particles of optimal size for alveolar delivery. Here we present a hand held,
      disposable, breath-actuated device incorporating this thermal aerosol technology,
      and its application to the delivery of alprazolam, an anti-panic agent, and
      prochlorperazine, an anti-emetic with recently discovered anti-migraine
      properties. Thermal aerosol particles of these drugs exist in an amorphous state,
      which results in remarkably rapid drug absorption from the lung into the systemic
      circulation, with peak left ventricular concentrations achieved within 20 s, even
      quicker than following rapid (5 s) intravenous infusion. Absorption of the
      thermal aerosol is nearly complete, with >80% absolute bioavailability found in
      both dogs and human normal volunteers.

PMID- 16886199
TI  - Polymeric systems for amorphous Delta9-tetrahydrocannabinol produced by a hot
      melt method. Part II: Effect of oxidation mechanisms and chemical interactions on
      stability.
AB  - The objectives of the present research investigations were to (i) elucidate the
      mechanism for the oxidative degradation of Delta(9)-tetrahydrocannabinol (THC) in
      polymer matrix systems prepared by a hot-melt fabrication procedure, and (ii)
      study the potential for controlling these mechanisms to reduce the degradation of
      THC in solid dosage formulations. Various factors considered and applied included
      drug-excipient compatibility, use of antioxidants, cross-linking in polymeric
      matrices, microenvironment pH, and moisture effect. Instability of THC in
      polyethylene oxide (PEO)-vitamin E succinate (VES) patches was determined to be
      due to chemical interaction between the drug and the vitamin as well as with the
      atmospheric oxygen. Of the different classes and mechanisms of antioxidants
      studied, quenching of oxygen by reducing agents, namely, ascorbic acid was the
      most effective in stabilizing THC in PEO-VES matrices. Only 5.8% of the drug
      degraded in the ascorbic acid-containing patch as compared to the control (31.6%)
      after 2 months of storage at 40 degrees C. This coupled with the cross-linking
      extent and adjustment of the pH microenvironment, which seemed to have an impact
      on the THC degradation, might be effectively utilized towards stabilization of
      the drug in these polymeric matrices and other pharmaceutical dosage forms. These
      studies are relevant to the development of a stable transmucosal matrix system
      for the therapeutic delivery of amorphous THC.

PMID- 16886200
TI  - Enhanced connexin 43 immunoreactivity in penumbral areas in the human brain
      following ischemia.
AB  - Astrocytes support neurons not only physically but also chemically by secreting
      neurotrophic factors and energy substrates. Moreover, astrocytes establish a
      glial network and communicate through gap junctions in the brain. Connexin 43
      (Cx43) is one of major component proteins in astrocytic gap junctions.
      Heterozygote Cx43 KO mice and astrocyte specific Cx43 KO mice exhibited amplified
      brain damage after ischemic insults, suggesting a neuroprotective role for
      astrocytic gap junctions. However, some reports mentioned unfavorable effects of
      gap junctions in neuronal support. Therefore, the role of astrocytic gap
      junctions under ischemic condition remains controversial. Since these studies
      have been performed using animal models, we investigated the Cx43 expression in
      human brain after stroke. Brain slice sections were prepared from pathological
      samples in our hospital. Embolic stroke brains sectioned because of the stroke
      were considered as acute ischemic models. Multiple infarction brains sectioned
      because of pneumonia or cancer were considered as chronic models. We observed the
      levels of Cx43 in both lesioned and intact areas, and compared them with acute
      and chronic models. As the results, astrocytes were strongly activated in
      penumbral lesions both of acute and chronic ischemic models. The Cx43
      immunoreactivity was significantly amplified in the penumbra of chronic model
      compared to that of the acute model. Neurons were well preserved in chronic model
      compared to acute model. These findings suggested that the brain may generate
      neuronal protection by increasing the levels of Cx43 and amplifying the
      astrocytic gap junctional intercellular communication under hypoxic condition.

PMID- 16886201
TI  - Functional changes in astroglial cells in epilepsy.
AB  - Epilepsy comprises a group of disorders characterized by the periodic occurrence
      of seizures, and pathologic specimens from patients with temporal lobe epilepsy
      demonstrate marked reactive gliosis. Since recent studies have implicated glial
      cells in novel physiological roles in the CNS, such as modulation of synaptic
      transmission, it is plausible that glial cells may have a functional role in the
      hyperexcitability characteristic of epilepsy. Indeed, alterations in distinct
      astrocyte membrane channels, receptors and transporters have all been associated
      with the epileptic state. This review integrates the current evidence regarding
      astroglial dysfunction in epilepsy and the potential underlying mechanisms of
      hyperexcitability. Functional understanding of the cellular and molecular
      alterations of astroglia-dependent hyperexcitability will help to clarify the
      physiological role of astrocytes in neural function as well as lead to the
      identification of novel therapeutic targets.

PMID- 16886202
TI  - Behavior of in vitro cultured ameboid microglial cells migrating on Muller cell
      end-feet in the quail embryo retina.
AB  - Ameboid microglial cells migrate tangentially on the vitreal part of quail embryo
      retinas by crawling on Muller cell end-feet (MCEF) to which they adhere. These
      microglial cells can be cultured immediately after dissection of the eye and
      isolation of sheets containing the inner limiting membrane (ILM) covered by a
      carpet of MCEF (ILM/MCEF sheets), to which the cells remain adhered.
      Morphological changes of microglial cells cultured on ILM/MCEF sheets for 4 days
      were characterized in this study. During the first minutes in vitro, lamellipodia
      bearing bipolar microglial cells became rounded in shape. From 1 to 24 h in vitro
      (hiv), microglial cells swept and phagocytosed the MCEF on which they were
      initially adhered, becoming directly adhered on the ILM. MCEF sweep was dependent
      on active cell motility, as shown by inhibition of sweep after cytochalasin D
      treatment. From 24 hiv on, after MCEF phagocytosis, microglial cells became more
      flattened, increasing the surface area of their adhesion to substrate, and
      expressed the beta1 subunit of integrins on their membrane. Morphological
      evidence suggested that microglial cells migrated for short distances on ILM/MCEF
      sheets, leaving tracks produced by their strong adhesion to the substrate. The
      simplicity of the isolation method, the immediate availability of cultured
      microglial cells, and the presence of multiple functional processes
      (phagocytosis, migration, upregulation of surface molecules, etc.) make cultures
      of microglial cells on ILM/MCEF sheets a valuable model system for in vitro
      experimental investigation of microglial cell functions.

PMID- 16886203
TI  - GFAP-expressing cells in the postnatal subventricular zone display a unique glial
      phenotype intermediate between radial glia and astrocytes.
AB  - Neural stem cells in the adult subventricular zone (SVZ) derive from radial glia
      and express the astroglial marker glial fibrillary acidic protein (GFAP). Thus,
      they have been termed astrocytes. However, it remains unknown whether these GFAP
      expressing cells express the functional features common to astrocytes. Using
      immunostaining and patch clamp recordings in acute slices from transgenic mice
      expressing green fluorescent protein (GFP) driven by the promoter of human GFAP,
      we show that GFAP-expressing cells in the postnatal SVZ display typical glial
      properties shared by astrocytes and prenatal radial glia such as lack of action
      potentials, hyperpolarized resting potentials, gap junction coupling, connexin 43
      expression, hemichannels, a passive current profile, and functional glutamate
      transporters. GFAP-expressing cells express both GLAST and GLT-1 glutamate
      transporters but lack AMPA-type glutamate receptors as reported for dye-coupled
      astrocytes. However, they lack 100 microM Ba2+-sensitive inwardly rectifying K+
      (K(IR)) currents expressed by astrocytes, but display delayed rectifying K+
      currents and 1 mM Ba2+-sensitive K+ currents. These currents contribute to K+
      transport at rest and maintain hyperpolarized resting potentials. GFAP-expressing
      cells stained positive for both K(IR)2.1 and K(IR)4.1 channels, two major K(IR)
      channels in astrocytes. Ependymal cells, which also derive from radial glia and
      express GFAP, display typical glial properties and K(IR) currents consistent with
      their postmitotic nature. Our results suggest that GFAP-expressing cells in
      concert with ependymal cells can perform typical astrocytic functions such as K+
      and glutamate buffering in the postnatal SVZ but display a unique set of
      functional characteristics intermediate between astrocytes and radial glia.

PMID- 16886204
TI  - The developmental expression of K+ channels in retinal glial cells is associated
      with a decrease of osmotic cell swelling.
AB  - A major function of glial cells is the control of osmotic and ionic homeostasis,
      mediated by K+ and water movements predominantly through inwardly rectifying K+
      (Kir) and aquaporin water channels. It has been suggested that K+ currents
      through Kir channels are implicated in the regulation of glial cell volume. Here,
      we investigated whether the developmental increase in Kir channel expression in
      Muller glial cells of the rat retina is associated with an alteration of cell
      volume regulation under anisoosmotic conditions. Around the time of eye opening
      at postnatal day (P) 15, developing retinal glial cells fully alter the profile
      of their membrane conductances, from a current pattern with prominent fast
      transient K+ and Na+ currents to a pattern of noninactivating currents through
      Kir and delayed rectifier K+ channels. Concomitantly, aquaporins-1 and -4 are
      expressed in the developing retina. This is accompanied by a conspicuous
      alteration of the swelling characteristics of cells; somata of immature glial
      cells in early postnatal retinas (P5-P15) swell under hypotonic stress but no
      swelling is inducible in mature cells at P18 and thereafter. However, glial cells
      at all developmental stages swell when their Kir channels are blocked by Ba2+.
      The postnatal maturation of Kir channel currents and volume regulation in retinal
      glial cells is delayed by visual deprivation. The data suggest that Kir channels
      are crucially involved in osmotic volume homeostasis of mature glial cells, and
      that the absence of Kir channels in immature cells is a major cause of their
      insufficient volume regulation.

PMID- 16886205
TI  - Role of N-cadherin in Schwann cell precursors of growing nerves.
AB  - In the present paper, we determine the localization and developmental regulation
      of N-cadherin in embryonic rat nerves and examine the role of N-cadherin in this
      system. We also identify a major transition in the architecture of embryonic
      nerves and relating it to N-cadherin expression. We find that in early embryonic
      nerves, N-cadherin is primarily expressed in Schwann cell precursors. Pronounced
      expression is seen at distal nerve fronts where these cells associate with growth
      cones, and the proximal nerve ends, in boundary cap cells. Unexpectedly, N
      cadherin is downregulated as precursors generate Schwann cells, coinciding with
      the time at which most axons make target connections. Therefore, glial N-cadherin
      expression is essentially restricted to the period of axon outgrowth. We also
      provide evidence that N-cadherin supports the formation of contacts between
      Schwann cell precursors and show that these cells are a favorable substrate for
      axon growth, unlike N-cadherin-negative Schwann cells. Induction of N-cadherin
      expression in Schwann cells by neuregulin-1 restores their ability to form
      contacts and support axon growth. Finally, we show that the loss of glial N
      cadherin during embryonic nerve development is accompanied by a transformation of
      nerve architecture, involving the appearance of endoneurial connective tissue
      space, fibroblasts, Schwann cell basal lamina, and blood vessels. Because N
      cadherin is likely to promote the extensive glial contacts typical of the compact
      embryonic nerve, we suggest that N-cadherin loss at the time of Schwann cell
      generation allows endoneurial space to appear between the glial cells, a
      development that eventually permits the extensive interactions between connective
      tissue and individual axon-Schwann cell units necessary for myelination.

PMID- 16886206
TI  - In vivo evaluation of a nasal insulin delivery system based on thiolated
      chitosan.
AB  - The aim of this study was the preparation and in vivo evaluation of a nasal
      insulin delivery system based on thiolated chitosan. 2-Iminothiolane was
      covalently attached to chitosan. The resulting conjugate (chitosan-TBA) exhibited
      304.9 +/- 63.5 micromol thiol groups per gram polymer. Microparticles were
      prepared via a new precipitation-micronization technique. The microparticulate
      delivery system comprised insulin, reduced glutathione and chitosan-TBA (Chito
      TBA/Ins) or unmodified chitosan (Chito/Ins) and control microparticles were
      composed of insulin and mannitol (Mannitol/Ins). Due to a hydration process the
      size of Chito-TBA/Ins and Chito/Ins microparticles increased in phosphate buffer
      pH 6.8 2.6- and 2.2-fold, respectively. Fluorescent-labeled insulin-loaded
      chitosan-TBA microparticles showed a controlled release over 4 h. Chito-TBA/Ins
      administered nasally to rats led to an absolute bioavailability of 6.9 +/- 1.5%.
      The blood glucose level decreased for more than 2 h and the calculated absolute
      pharmacological efficacy was 4.9 +/- 1.4%. Chito/Ins, in comparison, displayed a
      bioavailability of 4.2 +/- 1.8% and a pharmacological efficacy of 0.7 +/- 0.6%.
      Mannitol/Ins showed a bioavailability of 1.6 +/- 0.4% and no reduction of the
      blood glucose level at all. According to these findings microparticles comprising
      chitosan-TBA seem to have substantial higher potential for nasal insulin
      administration than unmodified chitosan.

PMID- 16886207
TI  - Invariant mantling of growth cones by Schwann cell precursors characterize
      growing peripheral nerve fronts.
AB  - Little is known about the cytoarchitecture of growth fronts in developing
      mammalian nerves. We report here the first quantitative, ultrastructural analysis
      of growth cones (GCs) and their immediate cellular and tissue environment at tips
      of growing nerves that are nearing their targets in fore limbs of E14 rat
      embryos. Schwann cell precursor (SCP) marker, p75 neurotrophin receptor, and
      growth cone marker, SCG10, were used to identify nerve fronts, respectively.
      Using confocal 3D reconstructions and immunoelectron microscopy, we found that
      growth cone and Schwann cell precursor migrate together at the nerve front, where
      growth cone contact adjacent growth cone and Schwann cell precursor with similar
      frequency. Schwann cell precursor are extensively connected by adherens junctions
      and form elaborate scaffolds that enmantle growth cone at nerve fronts, so that
      80% of the nerve front surface is covered by Schwann cell precursor. Although
      they interdigitate in complex ways among growth cone, the total contact area
      between growth cone and glial membranes is remarkably constant among the 100
      growth fronts analyzed. In contrast to this consistency, other growth cone
      contacts varied markedly from front to front such that the frequencies of GC-GC
      contacts are increasing proportional to their decreasing contacts with
      mesenchymal tissue. Thus, at the nerve front, it is the Schwann cell precursor
      that are most exposed to extracellular environment while forming a surprisingly
      invariant substrate for advancing growth cone. This study shows for the first
      time that Schwann cell precursor are close and consistent cellular companions of
      growth cone in their approach to their final targets in the developing limb and
      suggests a previously unappreciated role for Schwann cell precursor in growth
      cone advance through the limb mesenchyme.

PMID- 16886208
TI  - Pharmacokinetics and hepatic extraction of recombinant human parathyroid hormone,
      hPTH (1-34), in rat, dog, and monkey.
AB  - The pharmacokinetics (PK) and hepatic extraction (E(H)) of human PTH (1-34), hPTH
      (1-34), were characterized in rat, dog, and monkey, following intraportal (IPO)
      and intravenous (IV) bolus administration. hPTH (1-34) was administered to
      Sprague-Dawley rats (2, 10, 100 microg/kg), beagle dogs (3, 6 microg/kg), and
      rhesus monkeys (6, 30 microg/kg). Serum concentrations of immunoreactive hPTH (1
      34) were used to derive PK parameters. IPO bioavailability (F(IPO)) was
      determined by comparing dose-normalized serum exposure (i.e., AUC(IPO)/AUC(IV)).
      E(H) was estimated as 1-F(IPO). In all species, greater than dose-proportional
      increases in exposure (i.e., C(max) and AUC) were observed for both routes. Dose
      dependent disposition (i.e., time-average clearance (CL) and half-life (t(1/2))
      were observed in all three species. In rats, E(H) values of 71% (2 microg/kg),
      35% (10 microg/kg), and <1% (100 microg/kg) were obtained. In dogs, E(H) values
      of 90% (3 microg/kg) and 66% (6 microg/kg) were obtained. In monkeys, E(H) values
      of 25% (6 microg/kg) and <1% (30 microg/kg) were observed. In conclusion, hPTH (1
      34) is subject to hepatic first pass extraction in rat, dog, and monkey with
      evidence of saturation in the rat. Saturable hepatic extraction in dog and monkey
      is inconclusive due to the limited dose range investigated.

PMID- 16886209
TI  - Normal and abnormal early development of handedness.

PMID- 16886210
TI  - In situ fluorescence imaging of glutamate-evoked mitochondrial Na+ responses in
      astrocytes.
AB  - Astrocytes can experience large intracellular Na+ changes following the
      activation of the Na+-coupled glutamate transport. The present study investigated
      whether cytosolic Na+ changes are transmitted to mitochondria, which could
      therefore influence their function and contribute to the overall intracellular
      Na+ regulation. Mitochondrial Na+ (Na+(mit)) changes were monitored using the Na+
      sensitive fluorescent probe CoroNa Red (CR) in intact primary cortical
      astrocytes, as opposed to the classical isolated mitochondria preparation. The
      mitochondrial localization and Na+ sensitivity of the dye were first verified and
      indicated that it can be safely used as a selective Na+(mit) indicator. We found
      by simultaneously monitoring cytosolic and mitochondrial Na+ using sodium-binding
      benzofuran isophthalate and CR, respectively, that glutamate-evoked cytosolic Na+
      elevations are transmitted to mitochondria. The resting Na+(mit) concentration
      was estimated at 19.0 +/- 0.8 mM, reaching 30.1 +/- 1.2 mM during 200 microM
      glutamate application. Blockers of conductances potentially mediating Na+ entry
      (calcium uniporter, monovalent cation conductances, K+(ATP) channels) were not
      able to prevent the Na+(mit) response to glutamate. However, Ca2+ and its
      exchange with Na+ appear to play an important role in mediating mitochondrial Na+
      entry as chelating intracellular Ca2+ with BAPTA or inhibiting Na+/Ca2+ exchanger
      with CGP-37157 diminished the Na+(mit) response. Moreover, intracellular Ca2+
      increase achieved by photoactivation of caged Ca2+ also induced a Na+(mit)
      elevation. Inhibition of mitochondrial Na/H antiporter using ethylisopropyl
      amiloride caused a steady increase in Na+(mit) without increasing cytosolic Na+,
      indicating that Na+ extrusion from mitochondria is mediated by these exchangers.
      Thus, mitochondria in intact astrocytes are equipped to efficiently sense
      cellular Na+ signals and to dynamically regulate their Na+ content.

PMID- 16886211
TI  - Alterations in the oligodendrocyte lineage, myelin, and white matter in adult
      mice lacking the chemokine receptor CXCR2.
AB  - Oligodendrocyte precursor cell (OPC) proliferation and migration are critical for
      the development of myelin in the central nervous system (CNS). Previous studies
      showed that localized expression of the chemokine CXCL1 signals through the
      receptor CXCR2 to inhibit the migration and enhance the proliferation of spinal
      cord OPCs during development. Here, we report structural and functional
      alterations in the adult CNS of Cxcr2-/- mice. In Cxcr2-/- adult mice, we
      observed regional alterations in the density of oligodendrocyte lineage cells in
      Cxcr2-/- adult mice, with decreases in the cortex and anterior commissure but
      increases in the corpus callosum and spinal cord. An increase in the density and
      arborization of spinal cord NG2 positive cells was also observed in Cxcr2-/-
      adult mice. Compared with wild-type (WT) littermates, Cxcr2-/- mice exhibited a
      significant decrease in spinal cord white matter area, reduced thickness of
      myelin sheaths, and a slowing in the rate of central conduction of spinally
      elicited evoked potentials without significant changes in axonal caliber or
      number. Biochemical analyses showed decreased levels of myelin basic protein
      (MBP), proteolipid protein (PLP), and glial fibrillary acidic protein (GFAP). In
      vitro studies showed reduced numbers of differentiated oligodendrocytes in Cxcr2
      /- spinal cord cultures. Together, these findings indicate that the chemokine
      receptor CXCR2 is important for the development and maintenance of the
      oligodendrocyte lineage, myelination, and white matter in the vertebrate CNS.

PMID- 16886212
TI  - Peptide design of a competitive inhibitor for HMG-CoA reductase based on statin
      structure.
AB  - This study investigates a proposed design of a peptide sequence that is based on
      a bioactive conformation of statins that act as the competitive inhibitors of HMG
      CoA for HMGR. To bridge these heterogeneous organic compounds, a conformational
      aspect relating to an analysis of the flexibility of the peptide molecules and
      their occupied volumes was applied to the peptide design. The design criterion
      was formulated in terms of a proximity parameter (Pr), reflecting the probability
      of an active peptide conformation to approximate the statin. Through a structure
      functional analysis of previously synthesized peptides and statin molecules, nine
      peptides were selected for the peptide library. Comparing the calculated
      proximity parameters, four peptides (IAVE, YAVE, IVAE, and YVAE) from the library
      were selected and synthesized. In vitro assays elucidated the inhibition
      properties for HMGR that are exhibited by these peptides. Among all peptides,
      YVAE showed the highest ability to inhibit HMGR. A kinetic analysis revealed that
      this peptide is a competitive inhibitor of HMG-CoA with an equilibrium constant
      of inhibitor binding (K(i)) of 15.2 +/- 1.4 microM. The calculated coefficient
      correlation (R) between log (IC(50)) and the inverse value of proximity parameter
      (1/Pr) was found to be 0.99, indicating a high degree of correlation and efficacy
      of the given approach in the peptide sequence design.

PMID- 16886213
TI  - Structural and spectroscopic analysis of hydrogensquarates of glycine-containing
      tripeptides.
AB  - The hydrogensquarates of glycine-containing tripeptides glycylglycylglycine (H
      Gly-Gly-Gly-OH), glycylglycylmethionine (H-Gly-Gly-Met-OH), and
      methionylglycylglycine (H-Met-Gly-Gly-OH) have been characterized structurally.
      Quantum chemical ab initio calculations, solid-state linear-dichroic infrared (IR
      LD) spectroscopy, 1H and 13C NMR data, ESI-MS, HPLC-MS/MS, TGV, and DSC methods
      were employed. The structures consist in a positively charged peptide moiety and
      a negative hydrogensquarate anion (HSq), stabilized by strong intermolecular
      hydrogen bonds.

PMID- 16886215
TI  - JAK2V617F mutation can occur exclusively in the erythroid lineage and be absent
      in granulocytes and progenitor cells in classic myeloproliferative disorders.

PMID- 16886214
TI  - A long-lasting third complete remission after second autologous transplant
      followed by maintenance treatment with rituximab in a patient with diffuse large
      cell non-Hodgkin's lymphoma.

PMID- 16886216
TI  - Bacteriostatic polymer film immobilization.
AB  - Coatings of quaternary ammonium tertiary structures (QUATS) copolymerized with 4
      vinylbenzylthymine (VBT) exhibited high antimicrobial activity against
      Escherichia coli. Immobilization of QUATS improves environmental performance by
      preventing release of antibacterials to the environment, helping to preclude the
      emergence of resistant strains. The crosslinking immobilization scheme reported
      herein provides a more environmentally benign and more inexpensive synthesis than
      previously reported, thus reducing the use of solvents, energy, and production
      time. Development of water soluble, thymine-based photopolymers was inspired by
      the UV-induced 2pi + 2pi photocyclodimerization of thymine in DNA. Copolymers of
      4-vinylbenzylthymine and trimethylammonium chloride, triethylammonium chloride,
      or dimethyloctylammonium chloride were synthesized in different monomer ratios.
      The antibacterial properties were tested by coating VBT:QUATS in sterilized petri
      dishes, crosslinking under short UV light, spraying with aqueous suspensions of
      bacterial cells, air drying, and then applying agar media to promote bacterial
      growth. The plates were incubated for 24 h at 37 degrees C. The number of viable
      cells ranged from 17 to 0% growth. Immobilized VBT:QUAT copolymers are antiseptic
      surfaces that can be produced in an environmentally benign fashion.

PMID- 16886217
TI  - Application of the lithium and magnesium initiators for the synthesis of
      glycolide, lactide, and epsilon-caprolactone copolymers biocompatible with brain
      tissue.
AB  - The subject of this work is new method of the synthesis of biodegradable
      copolymers compatible with brain tissue. Copolymerization of glycolide with
      lactide was conducted in solution or in bulk in the presence of LiBu, LiAcac,
      MgBu(2), Mg(acac)(2) as initiators. In all cases, copolymers with molecular
      weight of 20000-40000 were obtained, which enables to use them as drug carriers.
      During the reactions of copolymer chain growth, the intermolecular
      transesterification occurs, changing the distribution of comonomeric units in
      copolymer chain. Magnesium initiators showed a lower contribution to
      transesterification in comparison with lithium and calcium compounds. The
      copolymerization of glycolide with epsilon-caprolactone using magnesium compounds
      as initiators was also described. The random glycolide/epsilon-caprolactone
      copolymer (10/90) obtained with MgBu(2) was used in in vivo study in the forms of
      microspheres and foils. Complete degradation of microspheres during 6 weeks was
      observed after the implantation to brain tissue. All implanted copolymers are
      compatible with brain tissue.

PMID- 16886218
TI  - Evaluation of chondrogenesis within PEGT: PBT scaffolds with high PEG content.
AB  - Porous poly(ethylene glycol) terephthalate:poly (butylene terephthalate)
      (PEGT:PBT) scaffolds with high PEG molecular weight (1000 g/mole) and PEGT
      content (60%) were fabricated using two different processes-paraffin templating
      and compression molding-for cartilage engineering applications. This polymer
      composition has previously been shown to enable chondrocyte adhesion and maintain
      differentiated phenotype in 2D monolayer culture. The influence of 3D polymer
      scaffold processing on the formation of cartilaginous tissue was studied by
      seeding primary immature bovine chondrocytes within cylindrical scaffolds in
      mixed flask reactors for 3 days, followed by cultivation in culture plates for a
      total of 10 or 24 days. Tissue-polymer constructs were evaluated morphologically
      by SEM and histology, and quantitatively for cellularity, total collagen, and
      glycosaminoglycan content, all of which remained statistically equivalent for
      each time point tested, irrespective of fabrication method. These data
      demonstrate that the polymers engineered for this study were able to support
      chondrogenesis independent of scaffold fabrication process, with the influence of
      pore architecture lessened by the highly hydrated scaffold microenvironments
      induced by high PEG content.

PMID- 16886219
TI  - Low-intensity ultrasound stimulates the viability and matrix gene expression of
      human articular chondrocytes in alginate bead culture.
AB  - We investigated the effects of low-intensity ultrasound (LIUS) on the activity of
      human articular chondrocytes isolated from osteoarthritis patients and cultured
      in the three-dimensional alginate beads. LIUS was treated at 0, 100, 200, and 300
      mW/cm(2) for 10 min everyday for 2, 7, or 15 days. LIUS induced the viability of
      cells only at day 15 but not until day 7 after treatment, when examined by trypan
      blue exclusion and LIVE/DEAD(R) assay kit. When examined at day 7, the
      proliferation of cells was not changed by LIUS in the (3)H-thymine incorporation.
      The expression of matrix producing proteins (type II collagen and proteoglycan)
      was clearly induced by 200-300 mW/cm(2) LIUS in the incorporation of
      radioactivity and Northern blot analysis. Although the expression of MMP-1, a
      matrix degrading protein, was decreased, that of TIMP-1, an inhibitor of MMPs,
      was not affected by LIUS. Histological analysis revealed an increase in the
      number and size of glycosaminoglycan-positive lacunae and cellular organelles,
      appearing as rough endoplasmic reticulum and mitochondria by LIUS. These results
      showed that the viability and metabolism of human articular chondrocytes in
      alginate culture was induced by LIUS treatment, suggesting that they could be a
      promising autologous source for cartilage tissue engineering.

PMID- 16886220
TI  - Osteoprecursor cell response to strontium-containing hydroxyapatite ceramics.
AB  - The objective of this study was to investigate the in vitro bioactivity of
      strontium-containing hydroxyapatite (Sr-HA), and its effect on cellular
      attachment, proliferation, and differentiation. The effect of Sr-HA has been
      compared with that of hydroxyapatite (HA), which is widely used in orthopedics
      and dentistry. Sr-HA ceramic containing 10 mol % was prepared. The bioactivity of
      Sr-HA was evaluated in vitro by immersion in simulated body fluid (SBF). After
      immersion in SBF, Sr-HA exhibited greater ability to induce apatite precipitation
      on its surface than did HA. The possible effects on cell behavior of Sr-HA were
      examined by culturing osteoprecursor cells (OPC1) on materials surfaces. Cell
      shape and cell-material interactions were analyzed by scanning electron
      microscope (SEM) and the MTT assay was used to determine cell proliferation on
      samples. When compared with HA, Sr-HA promoted better OPC1 cell attachment and
      proliferation, and showed no deleterious effects on extracellular matrix
      formation and mineralization. Confocal scanning microscopy was used to assess the
      expression of specific osteoblast proteins: alkaline phosphatase (ALP) and
      osteopontin (OPN). The results obtained indicate that the presence of Sr
      stimulates OPC1 cell differentiation, and enhances ALP and OPN expression.

PMID- 16886221
TI  - Gelatin-tricalcium phosphate membranes immobilized with NGF, BDNF, or IGF-1 for
      peripheral nerve repair: an in vitro and in vivo study.
AB  - In the present study, NGF, BNDF from the neurotrophin family and IGF-1 were
      covalently immobilized on gelatin-tricalcium phosphate (GTG) membrane using
      carbodiimide. We investigated the effects of these growth factors released from
      the GTG composites on cultured PC12 cells and sciatic nerve regeneration across a
      10-mm-long gap in rats. In PC12 cell culture, the total protein content and MTT
      assay indicated more cell attachment on the composites modified with growth
      factors. The IGF-1 group showed a higher survival promotion effect on PC12 cells
      than did BDNF and NGF groups. On the other hand, NGF released from the composite
      showed the highest level of neuritogenesis for PC12 cells in neurite outgrowth
      assay. In the animal study, the GTG conduits modified with various growth factors
      were well tolerated by the host tissue. In the regenerated nerves, the number of
      the axons per unit area of the BDNF group was significantly higher than that of
      NGF and GTG groups but similar to that of IGF-1 group. However, the average axon
      size was the largest in NGF group. This result was in concordance with the
      neurite outgrowth assay in which NGF showed the highest neuritogenic potential.
      In the assessment of motor and sensory recovery after nerve repair, conduits
      modified with various neurotrophic factors showed a more favorable outcome in
      compound muscle action potential. The BDNF group had a better gastrocnemic muscle
      weight ratio than blank GTG repair. Nevertheless, the different effects of GTG
      conduits modified with various neurotrophic factors on functional recovery cannot
      be simply illustrated in the sciatic function index.

PMID- 16886223
TI  - In vivo biostability of polyether polyurethanes with fluoropolymer surface
      modifying endgroups: resistance to biologic oxidation and stress cracking.
AB  - A series of Shore 80A polyether polyurethanes were synthesized with from 0 to 6%
      fluoropolymer surface modifying endgroups (SME) to provide the bulk properties of
      the polyurethane with the surface properties of the fluoropolymer. It was
      theorized that the fluoropolymer would migrate to the surface, forming a
      monolayer barrier to the oxidants and crack-driving agents released by
      macrophages and foreign body giant cells in vivo. In a 12-week biostability
      screening test, samples strained to 400% elongation appeared to be highly stable.
      In a longer-term study, the fluoropolymer SME significantly delayed, but did not
      completely prevent the onset of microcracking and the development of
      environmental stress cracking in strained samples. Even so, the 4 and 6% SME
      polymers explanted at 2 years performed significantly better than the control.
      FTIR analysis did not correlate with SME concentration, but increased hydrogen
      bonding index and loss of aliphatic ether (autoxidation) did correlate with the
      visual appearance and density of microcracks. Significant molecular weight
      reductions were seen for the SME-free control, but were small (within
      instrumental error) for the polymers with SME. The use of fluoropolymer as a SME
      does appear to be warranted as a means to improve polyether polyurethane
      biostability.

PMID- 16886222
TI  - Biomimetic artificial ECMs stimulate bone regeneration.
AB  - We demonstrate that a biomimetic polymer network is capable of affecting bone
      regeneration in vivo. Starting with a foundation consisting of an environmentally
      responsive poly(N-isopropylacrylamide-co-acrylic acid) hydrogel, we incorporated
      matrix metalloproteinase-13 (MMP-13) degradable crosslinkers and peptides
      containing integrin-binding domains (i.e., Arg-Gly-Asp) to create a biomimetic
      matrix designed to encourage osteoblast migration and proliferation. We
      independently tuned matrix stiffness and peptide concentration to generate a
      response surface model of osteoblast proliferation on different types of
      matrices. Osteoblast proliferation was significantly influenced by matrix
      stiffness (i.e., its complex modulus) and peptide concentration. When implanted
      in a rat femoral ablation model, these matrices induced bone regeneration only
      when protease degradable crosslinks were used to create the network. For the
      matrices with MMP-13 degradable crosslinkers, the bone formed had a trabecular
      like structure and was distributed throughout the marrow space. Based on the
      correlated effects of matrix stiffness and ligand concentration, the response
      surface model will facilitate improvements in the regenerative capacity of these
      artificial extracellular matrices.

PMID- 16886224
TI  - In vivo biostability of shore 55D polyether polyurethanes with and without
      fluoropolymer surface modifying endgroups.
AB  - Polyether polyurethanes are subject to autooxidation and environmental stress
      cracking (ESC) because of interactions with lysosomal oxygen-free radicals.
      Oxidation can also be catalyzed by and caused by direct (redox) reaction with
      transition metal ions (metal ion oxidation, MIO). The source of the ions is
      corrosion of metallic parts within an implanted device. A previous study on a
      Shore 80A polyether polyurethane modified with fluoropolymer surface modifying
      end groups demonstrated improved biostability over unmodified controls. We
      predicted that this could be extrapolated to the inherently more biostable Shore
      55D version (E55DF). While it is difficult to demonstrate significant
      biodegradation in the harder polymers within a reasonable time frame, we did see
      excellent biologic autooxidation and ESC resistance for both E55DF and its
      unmodified Shore 55D (P55D) control. E55DF was slightly, but significantly more
      resistant to MIO than P55D. This was particularly evident in molecular weight
      distributions with P55D exhibiting a large decrease in number average molecular
      weight compared to no change for E55DF. Both were markedly superior to the softer
      Shore 80A control. It does appear that one can extrapolate accelerated in vivo
      biostability results with the softer polymers to their harder analogues.

PMID- 16886225
TI  - Differential effects of agarose and poly(lactic-co-glycolic acid) on dendritic
      cell maturation.
AB  - Application of biomaterials in combination products in which the biomaterial is
      presented to the host with a biological component prompts the need for
      understanding the biomaterial-associated adjuvant effect in the immune response
      against antigens associated with such a product. We have previously demonstrated
      that a polymer commonly used in tissue engineering and vaccine delivery,
      poly(lactic-co-glycolic acid) (PLGA), exerts an adjuvant effect in vivo, which
      was supported by PLGA-induced dendritic cell (DC) maturation in vitro. In this
      study, the effects of agarose and PLGA on DC maturation were compared in vitro to
      establish differential biomaterial effects. Human monocyte-derived DCs were
      treated with agarose or PLGA microparticles or films, and their maturation effect
      was measured as expression of costimulatory and MHC class II molecules,
      allostimulatory capacity, and proinflammatory cytokine secretion. Direct
      comparison of DC maturation phenotype indicated that PLGA was a stronger stimulus
      of DC maturation than agarose, and this maturation was not affected by
      microparticle phagocytosis. However, agarose-treated DCs showed higher activation
      of nuclear factor kappaB (NFkappaB) 24 h after the initial stimulation of DCs.
      Taken together, these results demonstrate differential biomaterial effects on DC
      maturation, substantiating the maturation effect of PLGA, and provide screening
      methods for biomaterial adjuvant effect for applications in combination products.

PMID- 16886226
TI  - Evaluation of a femtosecond fiber laser for two-photon fluorescence correlation
      spectroscopy.
AB  - This work evaluates a femtosecond fiber laser for use in two-photon fluorescence
      fluctuation spectroscopy. Fiber lasers present an attractive alternative to
      Ti:Sapphire systems because of their compact size and portability.
      Autocorrelation of the second harmonic generation signal from the laser
      demonstrates that its stability is sufficient for two-photon fluorescence
      correlation spectroscopy. Fluorescence correlation spectroscopy autocorrelation
      traces were well fit by a Gaussian-Lorentzian squared model with a beam waist
      near the diffraction limit for the 810 nm wavelength. A photon counting histogram
      collected with this system also fit nicely to a single-species model, further
      demonstrating the quality of the focal shape. The authors conclude that the
      output from the femtosecond fiber laser is sufficiently stable and has a high
      enough quality beam shape for fluctuation fluorescence methods, and thus
      represents an effective, compact, readily portable two-photon excitation source.

PMID- 16886227
TI  - Sensilla and secretory glands in the antennae of a primitive ant: Dinoponera
      lucida (Formicidae: Ponerinae).
AB  - Morphology of the antennae of the female workers of the ponerine ant Dinoponera
      lucida was examined by light and scanning electron microscopy. In several
      antennomers, we found secretory gland cells of class I and III. Class III gland
      cells release their secretion through single pores in the antennal surface,
      whereas class I secretory cells are seen as tall epidermal cells close to the
      cuticle. Both gland types have weak reaction for total proteins and neutral
      polysaccharides. Six distinct sensilla types were observed: trichodea, chaetica,
      campaniform, basiconica, placodea, and coeloconica. The possible sensory
      functions of these sensilla and the gland functions are discussed.

PMID- 16886228
TI  - Atomic force microscopy characterization of Xenopus laevis oocyte plasma
      membrane.
AB  - We used atomic force microscopy (AFM) to characterize the plasma membrane of
      Xenopus laevis oocytes. The samples were prepared according to novel protocols,
      which allowed the investigation of the extra- and intracellular sides of the
      membrane, both of which showed sparsely distributed spherical-like protrusions.
      Regions with comparably sized and densely packed structures arranged in an
      orderly manner were visualized and dimensionally characterized. In particular,
      two different arrangements, hexagonal and square packing, were recognizable in
      ordered regions. The lateral dimension of structures visualized on the external
      side had a normal distribution centered on 25.5 +/- 0.3 nm (mean value +/- SE),
      whereas that on the intracellular side showed a normal distribution centered on
      30.2 +/- 0.8 nm. The height of the protrusions was 2-5 nm on the external side
      and 1-3 nm on the intracellular side. The mean number of structures on the
      external and intracellular sides of the plasma membrane was about 1000 microm(-2)
      and 850 microm(-2) respectively. Trypsin treatment greatly decreased the size of
      the membrane protrusions, thus confirming the proteic nature of the structures.
      These results show that AFM is a useful tool for structural characterization of
      proteins in a native eukaryotic membrane.

PMID- 16886229
TI  - A rapid method for diagnosing regional metastases of papillary thyroid cancer
      with morphometry.
AB  - Morphometry of the lymphoid cells was performed with a computerized image
      analyzer. Database formation was performed automatically using our own new
      software. The initial database of calculated mean values, of constructed
      histograms, of regression, and of discriminant analysis was transformed into a
      set of morphometric features. Eight morphometric features were selected for
      characterizing two separate populations of the lymphoid cells: one from the lymph
      node tissue with a malignant tumor and the other without any tumor (control). The
      eight features ensured the least overlap between the two groups of lymphoid
      cells. The eight features formed the basis of the decision criteria for
      identifying a patient with a malignant pathology. A weighting coefficient was
      calculated for each feature. It was ascertained that the presence of the regional
      papillary thyroid cancer metastases causes significant changes in the
      relationship between small (diameter </= 7.5 mum) and large (>7.5 mum) lymphoid
      cells of the cervical lymph nodes. The morphometric changes were assessed by our
      diagnostic index. The expert diagnostic system was developed on the basis of a
      set of quantitative features and their boundary values. This system highlights
      the morphometric changes in the population of the cervical lymph nodes lymphoid
      cell with metastases versus control. Clinical trials have shown that the expert
      diagnostic system's conclusions coincided with the histological diagnosis in all
      the cases. The expert diagnostic system, image processing, database formation,
      assessment of lymphoid cells morphometric features formed the basis of the rapid
      method of diagnosing regional metastases of papillary thyroid cancer. The
      diagnosis was performed in automatic mode. Taking into account that about 30-50%
      of aspiration smears contain only blood cells (absence of specialized cells such
      as thyrocytes), the use of our method should greatly improve the cytologic
      diagnosis of regional metastases of papillary thyroid cancer.

PMID- 16886230
TI  - Germinal vesicle chromatin configurations of bovine oocytes.
AB  - A common feature in the configuration of germinal vesicle (GV) chromatin in most
      species is that diffuse chromatin condenses into a perinucleolar ring during
      follicular growth; however, no such ring was observed in goat oocytes. Reports on
      whether bovine GV chromatin condenses into a perinucleolar ring are
      controversial. Besides, it is not known whether the perinucleolar ring in an
      oocyte represents a step toward final maturation or atresia. Changes in GV
      chromatin configurations during growth and maturation of bovine oocytes were
      studied using a new method that allows a clearer visualization of both the
      nucleolus and the chromatin after Hoechst and chromomycin A(3) staining. On the
      basis of the degree of condensation and distribution, the GV chromatin of bovine
      oocytes were classified into five configurations: NSN with diffuse chromatin in
      the whole nuclear area, N with condensed netlike chromatin, C with clumped
      chromatin, SN with clumped chromatin surrounding the nucleoli, and F with
      floccular chromatin near the nucleoli and near the nuclear envelope. Most of the
      oocytes were at the NSN stage in the <1.4-mm follicles, but the NSN pattern
      disappeared completely in follicles larger than 1.5mm. The SN pattern began to
      emerge in 1.5-mm follicles, and the number of SN oocytes increased while the
      number of oocytes with N and C configurations decreased with follicular growth.
      During maturation in vivo, while the number of N, C, and SN oocytes decreased,
      that of the F oocytes increased and reached maximum at 51h post prostaglandin
      injection. After that, the number of F oocytes decreased significantly because of
      germinal vesicle breakdown (GVBD). During maturation in vitro, GV chromatin
      configurations changed in a similar manner as during maturation in vivo. Fewer
      oocytes were at N, C, and SN stages, but more were at F and GVBD stages in the
      atretic than in the healthy follicles. Serum starvation slowed the F-GVBD
      transition of the in vitro maturing oocytes. More oocytes were of the SN or C
      configuration when ovaries were transported at 45-40 degrees C than at 35-30
      degrees C. Most of the heated oocytes were blocked at the SN stage during in
      vitro maturation. It is concluded that (i) bovine GV chromatin condenses into a
      perinucleolar ring during follicular growth; (ii) bovine oocytes were
      synchronized at the F stage before GVBD; (iii) oocyte GV chromatin configurations
      were affected by serum starvation, high temperature, and follicular atresia.

PMID- 16886231
TI  - Quantitative microscopy reveals 3D organization and kinetics of endocytosis in
      rat hepatocytes.
AB  - In order to demonstrate the power of quantitative microscopy, the endocytic
      apparatus of rat hepatocytes was reexamined using in situ liver and short term
      cultured hepatocyte couplets that were allowed to internalize endocytic markers
      for various time intervals. Correlative confocal light and electron microscopy
      demonstrate a tubulovesicular reticulum representing the endocytic apparatus.
      Volume and membrane area account for 2% of cell volume and 30% plasma membrane
      surface. Colocalization analysis demonstrated that pathway-specific ligands and
      fluid-phase markers enter EEA1-positive vesicles, the early endosomal
      compartment, immediately after internalization. These vesicles are translocated
      rapidly from basolateral to perinuclear and apical locations. Ligands are sorted
      within 5 min to their respective pathways. Sequential colocalization of an
      asialoglycoprotein-pulse with rab7 and lamp3 demonstrates that early endosomes
      change into or fuse with late endosomes and lysosomes. Alternatively, markers are
      sequestered into the common endosome consisting of rab11-positive, long tubules
      that originate from early endosomes and show an affinity for the transcytotic
      marker pIgA and its receptor. This compartment mediates transcytosis by
      delivering the receptor-ligand complex to the subapical compartment, a set of
      apical, rab11-positive vesicles, which are connected to the tubular reticulum. We
      conclude that vesicular traffic between preexisting compartments, maturation or
      fusion of endocytic organelles, and transport in tubules act in concert and
      together mediate transport between compartments of a tubulovesicular endocytic
      apparatus. In addition, we show that quantitative microscopy using high
      resolution data sets can detect and characterize kinetics of various parameters
      thus adding a dynamic component to 3D information.

PMID- 16886232
TI  - Surface ciliation of anuran amphibian larvae: persistence to late stages in some
      species but not others.
AB  - Scanning electron microscopy was used to examine the surfaces of 21 species of
      tadpoles from six families, from Gosner Stage 25/26 until close to metamorphosis.
      Contrary to most previous reports, ciliated epidermal cells persisted until late
      stages in many but not all species and not at all locations examined. The
      commonest location for ciliated cells was around the nostrils, suggesting a role
      in chemosensation. Ciliated cells also occurred around the circumference of the
      eye, suggesting a cleaning role. Several species had ciliated cells on the tail.
      The densest, most regular arrays of ciliated cells occurred in species that tend
      to hang motionless in still-water pools, suggesting a respiratory function for
      these cells.

PMID- 16886233
TI  - Anti-fatigue activity of a triterpenoid-rich extract from Chinese bamboo shavings
      (Caulis bamfusae in taeniam).
AB  - The anti-fatigue activity of a pentacyclic triterpenoid extract from bamboo
      shavings (EBS) from the bark of bamboo (Bambusa tuldoides Munro), was evaluated
      in BALB/c mice. EBS, isolated by the supercritical CO(2) fluid extraction (SFE)
      technique, was given to mice at concentrations of 0.04 (low-dose group), 0.08
      (middle-dose group) and 0.25 g/kg body weight (high-dose group). The anti-fatigue
      activity of EBS was estimated by the change in body weight, weight-loaded
      swimming test and climbing test, and corresponding parameters including serum
      urea nitrogen, hepatic glycogen and blood lactic acid were measured. The results
      showed that an appropriate level of EBS could prolong the weight-loaded swimming
      and climbing time, and had an active effect on the serum urea nitrogen, hepatic
      glycogen and blood lactic acid level in BALB/c mice, which significantly embodied
      the anti-fatigue activity of EBS. Overall, it is predicted that EBS, being a
      composition mainly containing a group of pentacyclic triterpenoids, and its main
      triterpenoid components have great potential for application in relevant fields
      for its anti-fatigue activity.

PMID- 16886234
TI  - Variation in pesticide hazard from vegetable production in Great Britain from
      1991 to 2003.
AB  - Pesticides pose a difficult problem for policy makers as society generally seeks
      to reduce any adverse impacts of their use, while industry claims they are
      important contributors to economic success. Attempts to direct policy according
      to scientific findings are hampered by the multidimensionality of the potential
      impacts of pesticides which may affect consumers, operators, wildlife and the
      environment. Pesticide risk indices seek to reduce these multidimensional impacts
      into a single dimension and have been increasingly used to understand variation
      in the hazard posed by pesticides at both field and regional level. This study
      uses one such risk index, the environmental impact quotient (EIQ), to estimate
      the hazard posed by pesticide usage from 1991 to 2003 on several vegetable crops
      grown in the UK. Results are reported for the EIQ and for the environmental
      impact (EI) for brassicas, peas, beans, onions, leeks, lettuce and endives. The
      EIQ is a dimensionless estimate of the toxicity of a product, while the EI, which
      combines the EIQ with data on actual usage, estimates the overall hazard of the
      use of a product. The exact trends in EIQ and EI varied with crop over the period
      1991-2003, but overall the EIQ decreased by 19% and the EI decreased by 34%.
      However, the mean EI per hectare decreased by only 3%. This suggests that some of
      the observed reduction in EI at the national level may be related more to
      decrease in crop area than changes in pesticide use and management. If these
      observed losses in crop area are being replaced by vegetable imports from
      overseas, then this raises the possibility that the UK is effectively exporting
      any problems related to pesticide use. The ethics of this remain unclear.

PMID- 16886235
TI  - Fluorescence and bioluminescence analysis of sequential UV-biological degradation
      of p-cresol in water.
AB  - The photolysis and Penicillium tardum H-2 degradation of p-cresol in water
      containing humic acids was investigated by fluorescence and bioluminescence
      methods. Humic acids extracted from peat (the Vasuygan bog, Tomsk region of
      Russia) induce the phototransformation of p-cresol. The influence of humic acids
      on the phototransformation of p-cresol under different irradiation conditions was
      investigated. Comparison of the data on the KrCl* (lambda = 222 nm) and XeCl*
      (lambda = 308 nm) excilamps light showed that the most effective p-cresol
      degradation was observed with mercury lamp irradiation in the presence of humic
      acids.

PMID- 16886236
TI  - Rendering in fetal cardiac scanning: the intracardiac septa and the coronal
      atrioventricular valve planes.
AB  - OBJECTIVE: In this study we aimed to apply spatio-temporal image correlation
      (STIC) rendering to visualize the virtual planes of the interventricular and
      interatrial septa (IVS, IAS) as well as the atrioventricular (AV) annuli plane
      just distal to the semilunar valves (coronal atrioventricular (CAV) plane) in
      normal and pathological fetal hearts, to ascertain whether these planes add to
      fetal cardiac examination. METHODS: Unselected gravidae presenting for anatomy
      scan or patients referred for fetal echocardiography in the second and third
      trimesters of pregnancy with suspected or diagnosed cardiac malformation were
      scanned using the five planes technique with the STIC modality to obtain cardiac
      volume sets for each patient. Rendering capabilities were employed to obtain the
      'virtual planes' to evaluate the IVS, IAS, AV annuli, and size and alignment of
      the great vessels. RESULTS: A total of 136 normal scans were performed to
      establish a learning curve for STIC acquisition and post-processing rendering and
      analysis. An additional 35 cases with cardiac anomalies were accrued. In 131/136
      (96.3%) normal scans the IAS and IVS were visualized successfully, while in
      127/136 (93.4%) normal fetuses the CAV plane was successfully visualized. In 13
      anomalous cases the IVS plane improved ventricular septal defect (VSD)
      evaluation, and in four the IAS plane contributed to foramen ovale evaluation.
      The modality improved visualization of the septa and the assessment of the
      defects, as well as the foramen ovale flap and pattern of movement of the foramen
      ovale. In five cases the CAV plane improved evaluation of the alignment of the
      major vessels in relation to the AV annuli, and in three the evaluation of the
      semilunar valves, with or without malalignment of the great vessels. CONCLUSIONS:
      Rendering STIC technology allows the visualization of virtual planes (IAS, IVS,
      AV annuli-CAV plane), which can clarify our understanding of anatomical defects
      and may improve communication with the management team and family.

PMID- 16886238
TI  - Interobserver agreement in hepatitis C grading and staging and in the Banff
      grading schema for acute cellular rejection: the "hepatitis C 3" multi
      institutional trial experience.
AB  - CONTEXT: Establishing adequate interobserver agreement is crucial not only for
      standardization of patient care but also to ensure validity of findings in multi
      institutional trials. OBJECTIVE: To evaluate interobserver agreement in assessing
      chronic hepatitis C (HCV) and acute cellular rejection (ACR) among 17
      hepatopathologists involved in the "Hepatitis C 3" trial. DESIGN: The trial is a
      randomized multicenter (17 institutions) study involving 312 patients undergoing
      transplantation for HCV. Patients are randomized to 3 treatment arms. For final
      data analysis, all biopsy specimens are reviewed by a central pathologist
      (G.J.N.). Recurrence of HCV is evaluated according to the Batts and Ludwig
      schema. The 1997 Banff schema is used to evaluate ACR. To assess interobserver
      agreement, hematoxylin-eosin-stained sections from 11 liver biopsy specimens (6
      HCV and 5 ACR) were sent by the central pathologist to 16 local pathologists from
      13 institutions. Statistical analysis was performed on raw ACR/HCV data as well
      as data grouped according to clinically significant primary endpoint cutoffs.
      RESULTS: Statistically significant agreement was found among all participating
      pathologists (P < .001). On kappa analysis, the degree of agreement was rated
      "moderate" for HCV grade and stage and ACR global grading (kappa = 0.30, 0.33,
      and 0.37, respectively). Interobserver agreement was weaker for rejection
      activity index scoring of ACR (kappa = 0.15). A stronger degree of agreement was
      found when scores were grouped based on endpoint cutoffs (kappa = 0.76 "almost
      perfect" for HCV and 0.62 "substantial" for ACR). CONCLUSIONS: An overall
      statistically significant interobserver agreement was found among 17 pathologists
      using the 1997 Banff schema and the Batts and Ludwig schema.

PMID- 16886237
TI  - [Standards, Options and Recommendations 2005 for a good practice in enteral
      nutrition in oncology (summary report.)].
AB  - CONTEXT: The "Standards, Options and Recommendations" (SOR) project, which
      started in 1993, is a collaboration between the French Federation of Cancer
      Centers (FNCLCC), the 20 French Regional Cancer Centers, and specialists from
      French public universities, general hospitals and private clinics. The main
      objective is the development of clinical practice guidelines to improve the
      quality of health care and the outcome of cancer patients. OBJECTIVE: To develop
      good practice guidelines for a good practice of enteral nutrition in oncology, in
      collaboration with three French learned societies involved in this area. METHOD:
      The methodology is based on a literature review and critical appraisal by a
      multidisciplinary group of experts who define the CPGs according to the
      definitions of the Standards, Options and Recommendations project. Once the
      guideline has been defined, the document is submitted for review by independent
      reviewers. RESULTS: The good practices suggested in the document approach seven
      topics: indications and counter-indications, conditions of the installation of
      the enteral nutrition, monitoring, prevention of complications, education of the
      patient, specificities of enteral nutrition in children and at home. In the
      setting of enteral nutrition, feeding tubes, type of insertion, enteral nutrition
      products, material and techniques of administration are described as well as the
      criteria permitting their selection.

PMID- 16886240
TI  - Physical exercise.

PMID- 16886239
TI  - Kicking off adaptive immunity: the discovery of dendritic cells.
AB  - In 1973, Ralph Steinman and Zanvil Cohn discovered an unusual looking population
      of cells with an unprecedented ability to activate naive T cells. Dubbed
      "dendritic cells," these cells are now known as the primary instigators of
      adaptive immunity.

PMID- 16886241
TI  - Science without the red tape.

PMID- 16886243
TI  - Spondylodiscitis: do not forget about endocarditis.

PMID- 16886242
TI  - Robert L. Lindon. 17th March 1924-13th February 2004.

PMID- 16886244
TI  - Giant cell arteritis presenting as painful third nerve palsy.

PMID- 16886245
TI  - No longer a child. Transitioning into adult care terrifies youth with HIV.

PMID- 16886246
TI  - Voices of hope. A group of young adults, out to change the world, one stop at a
      time.

PMID- 16886247
TI  - Having a ball. A look at an underground youth community that has taken HIV
      prevention and awareness into its own hands.

PMID- 16886248
TI  - "Live fast, die young." Born with HIV, a young man's story of addiction and
      survival. Interview by Enid Vazquez.

PMID- 16886249
TI  - Care of the HIV-positive adolescent. Developmental stages and provider
      sensitivity play a special role.

PMID- 16886250
TI  - Dating, youth, and HIV--from both sides. Teenagers try to make sense of it all.
      Interviews by Keith R. Green.

PMID- 16886251
TI  - Every hour. A young person becomes infected with HIV in this country every 60
      minutes.

PMID- 16886252
TI  - Metabolic FAQ. Frequently asked questions regarding metabolic syndrome.

PMID- 16886253
TI  - Kenya's tale. A short story for young people on courage, love and triumph over
      living with HIV.

PMID- 16886254
TI  - Politics and HIV: statement from Representative Rahm Emanuel (IL-5).

PMID- 16886255
TI  - How to find a doctor. AAHIVM offers badly needed credentials.

PMID- 16886256
TI  - AIDS policy update--2006 ushers in the era of "the medical approach". Whether the
      shift expands healthcare access or eases AIDS stigma remains to be seen.

PMID- 16886257
TI  - Prezista (darunavir, TMC-114) approved; may be important treatment advance.
AB  - A major new antiretroviral has been approved, for patients resistant to more than
      one protease inhibitor. There is no information yet on risk/benefit compared to
      standard treatments for first-line use. Tibotec, which developed the drug and is
      now part of Johnson & Johnson, showed price restraint and avoided setting a new
      record high price, which other companies have done.

PMID- 16886258
TI  - Study finds 3,000,000 years of life saved by HIV treatment in the U.S.
AB  - A research study published 25 years after the first report of AIDS found that at
      least 3,000,000 years of life have been saved in the U.S. by AIDS treatment. The
      study and accompanying editorial are free online from the Journal of Infections
      Diseases.

PMID- 16886259
TI  - Vaccine improves survival in monkey tests.
AB  - A vaccine tested at the U.S. NIAID clearly improved the survival of monkeys, a
      benefit not predicted by T-cell and viral load tests. It was predicted by
      measurements of memory T cells in the first few months of infection--giving
      important insights into how HIV disease develops, and how to test HIV vaccines
      early so that only the best candidates will go into large human trials.

PMID- 16886260
TI  - Improving medical communication online.
AB  - Medicine has not made full use of online information--and doing so might save
      thousands of lives. Part I looks at what has been most successful online in other
      fields, for background on how medical information could be improved.

PMID- 16886261
TI  - Brain drain adds to AIDS crisis in developing world.
AB  - Thousands of desperately needed doctors and other medical professionals leave
      poor countries because no one there can pay them, or provide safe and effective
      working conditions. Many go to English-speaking countries that do not train
      enough medical professionals themselves--such as the U.S., where a quarter of the
      doctors are foreign trained.

PMID- 16886262
TI  - Brazil: Gilead cuts tenofovir price in half.
AB  - A U.S. activist campaign, centered in the San Francisco area near Gilead's
      headquarters, helped get this major price reduction for Brazil's model HIV
      treatment program.

PMID- 16886263
TI  - [Tentative technological standard for tuberculin tests in the future].

PMID- 16886264
TI  - [Guideline for the use of Quantiferon TB-2G].

PMID- 16886265
TI  - Out of sight, out of mind: a dangerous practice.

PMID- 16886266
TI  - Cytokines in lymphoma.

PMID- 16886267
TI  - Dendritic cells in leukemia and lymphoma.

PMID- 16886268
TI  - Defining the cost of cure: infertility among female survivors of lymphoma.

PMID- 16886269
TI  - Something old, something new....

PMID- 16886270
TI  - Finding the best way to train the immune system against lymphoma.

PMID- 16886271
TI  - Treatment of acute myeloid leukemia in older adults: time to reflect?

PMID- 16886272
TI  - CNS infections: bugs and brains don't mix.

PMID- 16886273
TI  - Vitamin D and acute promyelocytic leukemia.

PMID- 16886274
TI  - Regression of large B-cell non-Hodgkin's lymphoma of stomach with HAART: case
      report and review.

PMID- 16886275
TI  - Hairy cell leukemia variant transforming into aggressive lymphoma with prostatic
      involvement in a patient with polycythemia vera.

PMID- 16886276
TI  - Safety of fractionated dose of rituximab in renal failure patients receiving
      hemodialysis.

PMID- 16886277
TI  - Metastatic pulmonary calcification in acute myeloid leukemia.

PMID- 16886278
TI  - Last word: Just say "go".

PMID- 16886279
TI  - Chronic neutrophilia preceding overt aggressive light chain multiple myeloma.

PMID- 16886280
TI  - PET positive progressive transformation of germinal centers masquerading as
      relapsed Hodgkin lymphoma post-autograft.

PMID- 16886281
TI  - BRCA2 mutation and the risk of hematologic malignancy.

PMID- 16886282
TI  - Non-Hodgkin's lymphoma presenting with granulomatous hepatitis and
      hemophagocytosis.

PMID- 16886283
TI  - T-cell receptor gamma and delta junctional gene rearrangements as diagnostic and
      prognostic biomarker for T-cell acute lymphoblastic leukemia.

PMID- 16886284
TI  - Multiple autoimmune phenomena in splenic marginal zone lymphoma.

PMID- 16886285
TI  - Multilobated mantle cell lymphoma.

PMID- 16886286
TI  - Bibliography of secondary sources on the history of dermatology: I. Journal
      articles in English supplemented through 2005 [corrected].

PMID- 16886287
TI  - Lichen planus.

PMID- 16886288
TI  - [Information, discussion, collaboration: Annual Congress of BeKD (Pediatric
      Nursing Profession Society) e.V].

PMID- 16886289
TI  - Retraction.

PMID- 16886290
TI  - Development and validation of diagnostic criteria for carpal tunnel syndrome.
AB  - PURPOSE: To develop clinical diagnostic criteria for carpal tunnel syndrome (CTS)
      that modeled the clinical diagnostic practices of experts. METHODS: Fifty-seven
      clinical findings associated with CTS had been ranked previously in order of
      diagnostic importance using Delphi as a method of establishing consensus among a
      panel of expert clinicians. The 8 most highly ranked criteria then were placed
      into all possible combinations to create 256 unique case histories. Two new
      panels of experts rated these case histories. One panel made a binary evaluation
      as to whether the case history did or did not represent CTS. This allowed the
      development of a logistic regression model that had the probability of carpal
      tunnel syndrome as the dependent variable and the weighted diagnostic criteria as
      the independent variables. This model then was validated against the judgments of
      the second panel of clinicians who estimated the probability of CTS for each of
      the same case histories. RESULTS: The correlation between the probability of CTS
      predicted by the model and the panel of clinicians was 0.71. CONCLUSIONS: The
      most important clinical diagnostic criteria for CTS as identified from a larger
      pool of potential diagnostic items through a consensus approach using Delphi were
      weighted and found to correlate well with the judgments of a new panel of
      clinicians. By improving the consistency of the diagnosis of CTS these criteria
      should lead to more effective treatment and a better understanding of the effect
      of workplace exposures in the development of this condition. A methodology that
      emphasizes a rigorous approach to item generation and item reduction through
      expert consensus, followed by validation, may represent a template for
      establishing consensus among experts on other controversial clinical issues. TYPE
      OF STUDY/LEVEL OF EVIDENCE: Diagnostic, Level I.

PMID- 16886291
TI  - Abstracts of the 2nd International Conference of Strategies in Tissue
      Engineering, May 31-June 2, 2006, Wurzburg, Germany.

PMID- 16886292
TI  - Balloon angioplasty or nitinol stents for peripheral-artery disease.

PMID- 16886294
TI  - The importance of prehospital ECGs.

PMID- 16886295
TI  - Prehospital ECGs & AMI research.

PMID- 16886293
TI  - Abstracts of the Annual Meeting of the Austrian Society of Hematology and
      Oncology, 27-29 April 2006, Wels, Austria.

PMID- 16886297
TI  - Abstracts of the International Students' Conference of Medical Sciences, Cracow,
      Poland, 6-8 April 2006.

PMID- 16886296
TI  - The future of STEMI response.

PMID- 16886298
TI  - Applying--not just implementing--a 12-lead program.

PMID- 16886299
TI  - Battlefield Charlotte revisited.

PMID- 16886301
TI  - Scottish study clearly demonstrates the benefit of a supervised exercise
      programme for women during treatment for breast cancer.

PMID- 16886300
TI  - Hungarian laboratory scientist use gene therapy to improve gemcitabine
      chemotherapy in glioma tumours.

PMID- 16886302
TI  - Seasonality of SIDS in Canada between 1985-1989 and 1994-1998.

PMID- 16886303
TI  - Abstracts of the XIV International Symposium on Atherosclerosis, Rome, Italy,
      June 18-22, 2006.

PMID- 16886304
TI  - The pandemic threat: are we prepared?
AB  - This paper will address the current pandemic threat from avian and other
      influenza viruses, the treatments available, federal, state and local response
      and planning, and the policy implications should a pandemic occur. The paper
      concludes with some discussion about where we are and where we need to go, and
      some recommendations for policymakers and legislators grappling with the issue of
      pandemic planning.

PMID- 16886305
TI  - [Image of the week. Septic arthritis and sepsis by MRSA of cutaneous region].

PMID- 16886307
TI  - Retail clinics: the competition heats up.

PMID- 16886308
TI  - New Hampshire takes on Rx data mining.

PMID- 16886306
TI  - Gastroesophageal reflux disease and irritable bowel syndrome: a common overlap
      syndrome.
AB  - Gastroesophageal reflux disease (GERD) and irritable bowel syndrome (IBS) are
      very common disorders in the general population. Symptoms of IBS are commonly
      encountered in GERD patients, and symptoms of GERD are not uncommon in IBS
      patients. GERD patients consistently report lower abdominal symptoms, which may
      be part of the spectrum of GERD symptoms. Alternatively, GERD and IBS may be two
      distinct manifestations of a similar underlying pathophysiologic process that can
      affect different levels of the gastrointestinal tract. Although the reason for
      the overlap observed between GERD and IBS remains to be elucidated, recent
      studies have demonstrated that GERD patients who also suffer from IBS-like
      symptoms perceive their GERD-related symptoms as more severe and are less likely
      to respond to antireflux treatment, as compared with those without IBS.

PMID- 16886309
TI  - Doctors vs hospital: will this battle become yours?

PMID- 16886310
TI  - See the world the locum way.

PMID- 16886311
TI  - Score one for CMS.

PMID- 16886312
TI  - Adding ancillaries. Ambulatory blood pressure monitoring.

PMID- 16886313
TI  - Selling to a hospital derailed my career.

PMID- 16886314
TI  - Dad's last days.

PMID- 16886315
TI  - What's a fact witness?

PMID- 16886316
TI  - [Treatment of snoring by a Herbst-activator. Satisfaction of patient and
      bedfellow].
AB  - Snoring is primarily a social problem which for instance brings considerable
      pressure on someone's conjugal relationship. Often treatment is demanded by the
      bedfellow. Patient as well as bedfellow needs to be involved in the treatment of
      the problem. In this study, twenty-three habitual snorers and their bedfellows
      completed a questionnaire concerning the effect of the treatment of snoring by a
      Herbst-activator before treatment and 3 and 6 months after treatment. Two-thirds
      of the patients and bedfellows were satisfied with the therapy results. The
      bedfellows exhibited an even more positive therapy effect than the patients.

PMID- 16886317
TI  - [Tooth brushing and gingival abrasion].
AB  - It has been known for some time that tooth brushing can have unwanted effects on
      the gingiva and hard dental tissues. The aim of this study is to evaluate two
      factors that may be of influence on the incidence of gingival abrasion during
      tooth brushing. The first factor being the possible influence of feedback through
      oral sensory perception and the second the possible abrasive effects of
      dentifrice. From the sensory feedback experiment it became clear that a
      significantly greater number of abrasions occurred when the test subjects would
      brush their own teeth than when they would have their teeth brushed by a dental
      hygienist. From the dentifrice experiment it became clear that the use of
      dentifrice has no significant effect on the occurrence of gingival lesions.

PMID- 16886318
TI  - [Dental hygienists vital to sound oral health care].
AB  - The first Dutch Dental Hygiene School was opened in 1968. Educating dental
      hygiene professionals with preventive qualifications was a well-considered
      decision. From the beginning on, the Dutch Dental Hygienists'Association has
      aimed at optimizing dental hygienists' role in preventive oral health care.
      Current developments, such as the introduction of a new national health insurance
      system and the rearrangement of oral health care, require reflection on the
      position of dental hygienists. Prevention should remain the core business of the
      dental hygiene profession. However, preventive oral health care has lost its
      social priority. Therefore, a new campaign preventing development of both old and
      new oral health threats should be initiated. In the opinion of the Dutch Dental
      Hygienists' Association, dental hygienists should be committed both to public and
      individual oral health prevention. The association pleads for the reinforcement
      of preventive oral health care for children and young adults, with a special
      focus on high-risk groups. Likewise, oral health care for elderly people should
      receive more attention.

PMID- 16886319
TI  - [Dissertations 25 years after date 8. Non-odontogenic cysts of the oral regions].
AB  - Non-odontogenic cysts are rare. Today, only 2 of the 18 non-odontogenic cysts
      that were described in 1982 are still classified as such: the nasopalatine duct
      cyst and the nasolabial cyst. The others are now classified in other groups. In
      the general practice the nasopalatine duct cyst is mostly seen as a swelling of
      the palate, just behind the central incisors. The nasolabial cyst is more rare
      and can be characterized as a paranasal swelling. Treatment of both cysts
      consists of surgical removal by intraoral approach. It is advisable to refer all
      cases of suspected non-odontogenic cysts, with the exception of the mucosal
      antral cyst, to an oral and maxillofacial surgeon in order to have the diagnosis
      confirmed.

PMID- 16886320
TI  - [Diagnostic considerations concerning a case of an unusual gingivitis].
AB  - A young woman presented a severe gingivitis that wouldn't respond to antibiotics
      prescribed by her general practitioner. Thorough clinical examination showed
      atypical gingival inflammation. In such unusual cases a careful anamnesis is
      essential in determining appropriate continued diagnostic procedures. Eventually,
      acute myeloid leukaemia was diagnosed. Since the diagnosis of gingival disease
      primarily lies with the dentist, it is important to be able to consider any
      unusual aspects of gingivitis within a dental office.

PMID- 16886321
TI  - [A girl with congenital hemifacial hypertrophy].
AB  - A girl with congenital hemifacial hypertrophy had been observed and treated by a
      multidisciplinary team for craniofacial disorders in an academic medical centre
      since birth. At the age of 8 she was treated on account of considerable facial
      asymmetry and multiple intraoral problems. The two-step surgery involved
      reduction of the maxilla and the zygoma, reduction of soft tissues, removal of
      the teeth on the affected side, correction of the alveolar ridges of the maxilla
      and the mandible and placement of oral implants. After a healing period of 4
      months fixed partial dentures were constructed on the implants.

PMID- 16886322
TI  - [Regulation of the immune response to intestinal nematode infections in mice].
AB  - Control of parasitic infections is dependent on mechanisms that limit invasion,
      reproduction or survival of the parasite, including elevated serum IgE,
      eosinophilia and intestinal mast cell hyperplasia. Studies with mice infected
      with Heligmosomoides polygyrus, Trichuris muris, Nippostrongylus brasiliensis and
      Trichinella spiralis have provided considerable information about immune
      mechanisms correlated with resistance and susceptibility. Activation and cytokine
      secretion of distinct Th cell subset leads to the generation of effective or
      ineffective responses resulting in clearance of the parasite load or maintenance
      of chronic infection. The induction of differential responses remains to be
      determined but is likely to be influenced at a number of levels including the
      host genetic background, involvement of accessory cells, activation of co
      stimulatory molecules on antigen presenting cells. The regulation of responses to
      intestinal nematode infections is discussed.

PMID- 16886323
TI  - [Knowledge of the mites of the family Spinturnicidae (Acari: Mesostigmata) in
      Poland].
AB  - This paper presents a checklist of the mites of the family Spinturnicidae set on
      the basis of the whole Polish literature review. The checklist is supplemented
      with new data about bat hosts and localities in Poland.

PMID- 16886324
TI  - Occurrence of prostaglandins and other eicosanoids in parasites and their role in
      host-parasite interaction.
AB  - Prostaglandins have been already pretty well recognized as metabolic regulators
      in vertebebrata tissues mainly in mammals. I.ess reports concerned the occurrence
      of prostaglandins in invertebrates. In the present review we summarise literature
      data about the presence of prostaglandins and other eicosanoids in various groups
      of parasites and their possible role in host-parasite interaction. Prostaglandins
      have also been found in very primitive organisms as bacteria, varions plants and
      protozoa. We summarise that prostaglandins seem to be a very ancient group, going
      back to the roots of evolution. They are as universal in cell physiology as DNA
      in genetics. In host-parasiter eicosanoids also parasitic origin, play an
      important role as a modulators of hosts immune responsiveness.

PMID- 16886325
TI  - [Impact of heavy metals on the host-parasite system].
AB  - Now in the time especially intensive development of industry the question of
      environment pollution became very important. According to review of the problem
      heavy metals are one of the most hazardous constituents of xenobiotics. Their
      toxic effects, among other, are manifested directly on the elements of the immune
      system as well on the modification of the immune response. The influence of heavy
      metals on the host-parasite system is rather poorly recognized and here we are
      discused about it, according to literature and own experience. Special attention
      is paying to their impact on the immune response of infected and treated with
      lead, cadmium or mercury host and on the parasite. The definitive host eg. fishes
      and their some parasite can be used as potential accumulation indicators of
      aquatic environment of heavy metal pollution.

PMID- 16886326
TI  - [Identification of Toxoplasma gondii antigens recognized by specific T
      lymphocytes].
AB  - The paper presents chosen experimental strategies for identifying of Toxoplasma
      gondii antigens recognized by specific T lymphocytes.

PMID- 16886327
TI  - Prevalence of Toxocara canis infection in dogs in the Warszawa area.
AB  - The evaluation of Toxocara canis infection in stray dogs from two shelters and
      private owners dogs in the Warszawa district was the aim of this study. In 1998
      five hundred faecal samples were examined. The homeless dogs were found more
      infected than those kept as pets. T. canis was recorded in 3.4% and 8.8% of stray
      dogs from the shelters and in 0.4% of animals from flats. The higher prevalence
      of infection in homeless dogs was due to high density of dogs population, worse
      environmental condition and irregular anthelmintic treatment in the shelters when
      compare with housed dogs.

PMID- 16886328
TI  - [The risk factors of Toxocara canis infestation in population of patients from
      the Lublin region].
AB  - The risk factors of Toxocara canis infestation were assessed among population of
      patients from the Lublin region. Sera from 151 patients suspected of toxocarosis
      were tested on the presence of the specific antibodies by ELISA (Biokema-Bordier,
      Switzerland). Sera from 74 women and 77 men were collected (mean: 24 years;
      range: 0-74 years). Women sera were found positive in 27 cases (36.5%) and men in
      34 cases (44.2%). Positive results were found in the following age groups: young
      people up to 15 years--34 positive from 71, people from 16 to 30 years old--7
      from 33, people from 31 to 45 years old--9 from 24 and people older than 45 years
      -11 from 23. Patients suspected of ocular larva migrans were found serologically
      positive in 37 cases from 98. Among patients with eosinophilia 8 positive cases
      were found from 17 (47.1%). Rural inhabitants were found positive in 41 cases
      from 73, whereas inhabitants of small towns in 17 cases from 55 and inhabitants
      of Lublin city (population nearly 400,000) in 3 cases from 23. This relationship
      was statistically significant (p<0.01). The difference between the group of
      living in a house (52% positive cases) compared to those living in flats (18%
      positive cases) was also statistically significant (p<0.001).

PMID- 16886329
TI  - [Genetic diversity of Borrelia burgdorferi sensu lato in Ixodes ricinus ticks
      collected in north-west Poland].
AB  - Borrelia burgdorferi sensu lato (s. l.), the etiological agent of Lyme diesease,
      is transmitted by the bite of Ixodes ricinus. During May and September 1999,
      field surveys on Lyme disease spirochetes were conducted in three locations of a
      region of north-west Poland, known as recreational districts visited by many
      people. The ticks Ixodes ricinus were collected in natural habitats by dragging a
      flanel cloth over the vegetation. Sex and developmental stage of each tick were
      determined. Based on a polymerase chain reaction test with primers that recognize
      a chromosomal gene of all strains, out of the total 1414 specimens collected, 126
      (8.9%) were found to be infected. The species B. burgdorferi s. l. comprises at
      least three pathogenic genomospecies, B. burgdorferi sensu stricto (s. s.),
      Borrelia garinii, and Borerelia afzelii, witch could be distinguished in nested
      PCR tests with species-specific primers. B. burgdorferi s. s. was most prevalent
      (96% of infected ticks), followed by B. garinii (1.3%), and B. afzelii. was not
      found. Of the infected ticks, over the 99% were infected with a single species,
      one specimens was infected with two species. For 4 ticks, the infecting species
      could not be identied. The difference in rates of prevalence was observed among
      the tree locations (17%--5.3%--3.2%).

PMID- 16886330
TI  - Beta 2-microglobulin and neopterin in patients with giardiasis.
AB  - The aim of the study was to evaluate serum beta 2-microglobulin (beta-2m) and
      neopterin (NPT) in in patients with giardiasis. Twenty-two patients with
      giardiasis were examined and compared with twelve healthy subjects as a control
      group. Serum beta-2m and NPT concentration were determined twice: at the moment
      of diagnosis of giardiasis and six months after antiparasitic treatment with
      metronidazole. It was shown that serum beta-2m concentration in patients with
      giardiasis was remarkably elevated. It decreased significantly, but six months
      after treatment it was still higher as compared to the control group. However,
      serum NPT before anti-parasitic treatment was slightly lower than in the control
      group, but after elimination of Giardia an increase of NPT concentration above
      control values was observed. It is concluded that Giardia infection leads to long
      lasting disturbances in the immunological status of the host and may influence
      macrophage function and downregulate their parasiticidal effects.

PMID- 16886331
TI  - [Sick rate of scabies among people in the city of Katowice].
AB  - The incidence of scabies disease was analysed among women, men and children in
      Katowice in 1993-1997. The materials came from the Municipal Hospital of
      Dermatology and from the Clinic of Dermatology in Katowice. From the analysis of
      materials follows that the precentage of infected women and men was low in the
      studied period and fuctuated between 0.5 % and 1.8 %. Higher percentage appeared
      among children. The precentage of hospitalized children was higher (9.4 %-12.6 %)
      than at children from the clinic (2-2.4 %). The most cases concerned children
      between 1 and 5 years old.

PMID- 16886332
TI  - [Influence of zinc and lead ions on the development of eggs of Ascaris suum
      (Nematoda)].
AB  - The objective of this work was to examine the influence of heavy metals ions,
      zinc and lead, in external environment on the development of Ascaris suum to
      invasive stage. The culture mediums contained 25.5, and 0.5 mM Pb(NO3)2 or ZnSO4.
      After 6 weeks of development in 26 degrees C in the control 75.17% of eggs
      reached the invasive stage. Ions of lead and zinc, in a way depending on
      concentration inhibited development of embryos. The invasive stage in the
      presence of 25.5 and 0.5 mM Pb(NO3)2 were achieved by 37.89% , 44,75% and 64.63%
      of eggs and in ZnSO4 solutions with the same concentrations of ions 45.40%,
      50.36% and 66.61% respectively. Many of eggs in 25 mM solutions of both metals
      stopped at the blastula stage.

PMID- 16886333
TI  - Hepatozoon kabeenin. sp. (Protozoa: Apicomplexa; Hemogregarina) from the sedge
      warbler, Acrocephalus schoenobaenus (Aves: Passeriformes).
AB  - New species, Hepatozoon kabeeni was described in blood of Sedge Warbler
      Acrocephalus schoenobaenus. The parasite species was detected in two populations
      of Sedge Warbler in NE and SW parts of Poland. Hepatozoon kabeeni was found
      respectively in 36.0% (n=25) and 28.6% (n=28) of individuals.

PMID- 16886334
TI  - [Invasion of Dermanyssus gallinae (De Geer, 1778) in poultry farms in the Torun
      region].
AB  - The studies were conducted in three big fully automaticised egg-laying farms
      within the boundaries of Torun Voivodship, where Dermanyssus gallinae (DE GEER
      1778) was present. The increased invasion of the parasite on one of the farms
      resulted in the presence of all clinical symptoms of dermanyssosis. A
      considerable decrease in the body weight, anaemia and organism exhaustion were
      observed. A growth in the hens' death rate from 1% (when they were not
      contaminated) to 4% was observed. There was also a decrease in egg-laying,
      particularly in its top phase. When breeding farms are not contaminated, egg
      laying amounts normally to 91-93%, whereas in the contaminated farm the
      percentage lowered to 80-82%. The hens' death rate, a decrease in the egg
      production as well as a fall in the productive cycle by two months resulted in
      economical losses suffered by the farm owner. Having excluded the treatment
      costs, the sum amounted to c. 36,000 PLN in a single production cycle. To fight
      the parasite effectively, cleansing frequency, desinfecting with Wirkon and
      Pollena Jod K or caustic soda, and disinsectization with Neguvon and Alfasep 10WP
      were increased.

PMID- 16886335
TI  - [Conference about Echinococcosis caused by Echinococcus multilocularis].

PMID- 16886336
TI  - [Twentieth report from the WHO Expert Commitee on Malaria. WHO technical report
      No. 892, Geneva, 2000, 71 pp].

PMID- 16886337
TI  - [II nd International Seminar: "Arthropods - parasitics, alergogenics and
      poisonous - medical and sanitary significance" in Kazimierz Dolny, Poland].

PMID- 16886338
TI  - [Strongyloidosis. Part VII. Epidemiology and prevention (1)].
AB  - The source of invasion of Strongyloides stercoralis and the routes of
      transmission strongyloidosis were presented. The survival, development and
      behavior forms parasitic and free-living generation of S. stercoralis in soil and
      host was also described.

PMID- 16886339
TI  - [Parasites as the vectors in an aqueous environment].

PMID- 16886340
TI  - [Effect of ketotifen on the immune response in BALB/c mice infected with
      Trichinella spiralis].
AB  - Infection with Trichinella spiralis in mice generates Th-2 mediated response,
      which controls effector mechanism operating in the intestine. It is associated
      with a pronounced intestinal mastocytosis, eosinophilia and destruction of
      intestinal epithelial layer during expulsion of parasite from the gut. It is
      believed that protection is dependent on non-specific inflammatory reaction
      mediated by mast cells. Furthermore, the higher serum levels of parasite specific
      IgG1 and IgG2a and also mucosal IgA response were related to the course of
      infection. Inhibition of humoral and cellular immune responses using ketotifen as
      anti-allergic compound, resulted in the greater worm burden and worm size, but
      not in the significant prolongation of intestinal phase. Moreover, in treated
      mice epithelial layer of the gut was protected from destruction provoked by the
      nematode. As interaction between effector leukocytes and antibodies were not
      effective it was proposed that other mechanisms, not related to hypersensitivity
      or conventional inflammatory response regulated the level of infection. The
      immunological and physiological phenomenons are discussed in terms of events
      associated with protection to the parasite. Possibly, immunoregulatory capasity
      of the nematode is involved in the induction of multiple mechanisms operated
      during infection.

PMID- 16886341
TI  - Variability of the reproductive system of Piscicola respirans (Troschel, 1850)
      (Hirudinea, Piscicolidae).
AB  - The studies on the reproductive system of P. respirans, based on 115 specimens,
      have revealed its considerable variability. Two main types of the system can be
      distinguished: 1) ovaries reaching the first pair of testes, ejaculatory ducts
      symmetrical, no seminal vesicles (juvenile individuals), 2) ovaries reaching the
      first pair of testes, ejaculatory ducts symmetrical, seminal vesicles reaching
      the ends of ovaries (adults individuals). The structure of the reproductive
      system is correlated with the individual size and age. Because the reproductive
      system of P. respirans as described by BRUMPT (1900) and SKET (1968) based on
      type specimens designated by them, is found only in a small fraction (c. 4-8%) of
      specimens, a redescription of the species is necessary, best based on a neotype
      series.

PMID- 16886342
TI  - Parasitofauna of the nine-spined stickleback from the Gulf of Gdansk and the
      mouth of Dead Vistula.
AB  - Four species, one subspecies and one parasite marked to the genus were collected
      from the nine-spined stickleback Pungitius pungitius L. from the Gulf of Gdansk
      and the mouth of Dead Vistula. Nine-spined stickleback was noted as a new host in
      Polish coastal water for five parasites: Glugea anomala (Microsporidia),
      Diplostomum spathaceum (Digenea-metacercariae) and Apatemon sp. (Digenea-incysted
      metacercariae), Hysterothylacium aduncum (Nematoda-third stage larvae) and
      Thersitina gasterostci (Copepoda). Earlier in this area have been obserwd only
      ciliates Tnchodina domerguei.

PMID- 16886343
TI  - [Relationships between the prevalence of Toxocara eggs in dogs' faeces and soil].
AB  - Toxocariasis is a cosmopolitan infection of dogs and cats. Humans (mainly
      children) become infected by accidentally ingesting embryonated eggs from the
      environment. The studies were conducted on the role of dogs in the epidemiology
      of human toxocariasis. A total of 112 soil samples and 110 fecal samples were
      collected from the same public places in Poznan, including backyards in the
      centre of the city, playgrounds and public squares grounds. Of these soil
      samples, 6.3 % were positive for Toxocara spp., 1.8 % for Trichuris vulpis. Fecal
      examination revealed that 0.9 % samples were positive for Toxocara canis, 1.8 %
      for Trichuris vulpis and 0.9 % for Toxascaris leonina.

PMID- 16886344
TI  - [The influence of different management systems on the infection level of some
      gastrointestinal parasites in sheep in southern Poland].
AB  - On the basis of the fecal egg counts, larval cultures and necropsies the
      infection of coccidia, tapeworms and gastrointestinal nematodes in dams and lambs
      under extensive and intensive management systems were estimated. During 1994 and
      1995 total of 1740 coproscopic analyses were done. It was state, that in
      extensive farms the prevalence and EPG of gastrointestinal nematodes was higher
      in comparison with intensive management system (38.2-86% and 13.9-71.9% and 105
      355 EPG and 33-131 EPG respectively). Similarly prevalence of tapeworms 0-18.2%
      and 1.3-8.3% respectively. Prevalence and intensity of coccidia was lower in
      extensive farms (20-78,5% and 83-482 OPG) comparing with intensive management
      system (38.2-88% and 139-2846 OPG). Predominant nematode species in both
      management systems were those from genes Haemonchus, Teladorsagia,
      Trichostrongylus, Cooperia and Nematodirus. One species--Nematodirus battus was
      found new for Poland.

PMID- 16886345
TI  - [The occurrence of Ixodes ricinus in the selected recreative areas in the
      province of Szczecin. Part II].
AB  - The aim of the study was to estimate the occurrence (the quantative and rate
      percent) of Ixodes ricinus in the popular recreation areas in Szczecin (Arkonka,
      Osow, Glebokie, Landscape Park of Szczecin, Dabie Forest Park, Zdroje Forest
      Park) and in province of Szczecin (Forest of Goleniow, Insko, Pobierowo, Chojna).
      Investigations were performed in 1998 year, twice on each places; in May/June and
      repeted in September/October. The temperature and humidity of air were measured.
      Obtained specimens were regard of sex and growing stage during each collection. A
      total of 2.055 specimens collected 49% were nymphs, 13.9% female, 11.3% male and
      25.8% larvaes. The nymphs the most frequently were in spring when humidity of air
      was 55% and temperature 24 degrees C. The larvaes, in autumn were most frequently
      (31.4%) then in spring (20.5%) when the temperature of the air was 18-22 degrees
      C, and the humidity from 60 to 85% during the collections.

PMID- 16886346
TI  - [Damalinia meyeri (Tasch.) (Mallophaga) of fallow deer (Dama dama) from
      Pomerania].
AB  - After examination of 202 fallow deers, in 15 of them D. meyeri was founded.
      Prevalence amounted to 7% intensity ca. 5.5 specimens.

PMID- 16886347
TI  - [Demodex ssp. (Acari, Demodecidae) in Mus musculus from Poland].
AB  - Two species (Demodex arvicolae and D. flagellurus) were collected in Mus musculus
      the first time in Poland. Also Myobia musculi was noted.

PMID- 16886348
TI  - [Acarine disease of bees (acariasis) in Poland during 1973 to 1975].
AB  - Acariasis is on the list B of the Office of International Epizootics.
      Epizootiological bulletins of the Veterinary Department in the Ministry of
      Agriculture of Poland were studied and occurrence of acariasis was noted. Acarine
      disease of bees during 1973 to 1975 in Poland was noted only in some
      voivodeships. Acariasis was diagnosed every year in voivodeships: Katowice,
      Krakow, Lublin, Opole, Wroclaw and Zielona Gora (South Poland).

PMID- 16886349
TI  - [Regulation of defence and allergic reaction in infections with parasites].
AB  - Cytokines regulate development, differentiation and expression of effector
      function of the immune system. The profile of immune reactions depends on
      cytokine contents at the recognition of parasite. However, parasites themselves
      can modify immunological events and favourite these, which allow them to survive.
      The host immune defence can be transformed into the chronic reaction.
      Inflammatory reactions result from the recruitment of different cells, to the
      site where worms are localised. The eosinophil and mast cell migration
      preferentially is induced. These cells play also a major role in immediate
      allergic responses. Mast cells can bind allergen-specific IgE to their
      FcepsilonRI, the high affinity receptor for IgE. Eosinophils, through their
      receptors for IgG1, IgG2, IgA and IgE are mainly involved in the cytotoxic
      reaction directed against parasites. Crosslinking of these receptors by antigen
      binding will lead to subsequent release of stored mediators and cytokines.
      Granular materials released from mast cell accelerate inflammatory reaction and
      in the case of intestinal worm parasites may be involved in the expulsion
      phenomenon. However these cells may also induce Th2 related immunological
      response because they produce and release of IL-4. Eosinophils are required into
      the tissue and release cytotoxic and stress proteins including reactive oxygen
      species. Parasites are destroyed but accelerated reaction results in the
      destruction of host proteins and cells. Antibodies, cytokines, chemokines and
      adhesion molecules are essential for elevation of defence against parasites. The
      role of cytokines, emphasizing IL-5, and function of eosinophils, mast cells and
      IgE are discussed in terms of induction and effector mechanisms during parasite
      infections.

PMID- 16886350
TI  - [The new generations of vaccines against parasites].
AB  - The protection of humans and domestic animals against parasitic infections
      remains a major goal, especially in light of developing of drug resistant strains
      in many parasite species. "Classic" vaccines are based on attenuated infective
      stages of protozoan and helminth parasites. Although such vaccines are effective
      in confering host immunity against several protozoan (coccidiosis, giardiosis,
      toxoplasmosis) diseases and one helminth (dictyocaulosis) they are very unstable
      and expensive. Recombinant techniques enable to obtain protective antigens
      quickly and in considerable quantities, cultivating of the bacteria and
      purification of the recombinant protein is less expensive than the maintenance of
      host animals and isolation of the protective antigens from harvested parasites.
      Moreover, the cloned protective antigens may be deprived of epitopes responsible
      for immunopathology. However, at present only one anti-parasite recombinant
      protein vaccine is commercially available (TickGARD). Such a situation may result
      from that many protective parasitic antigens cannot be expressed in bacteria or
      yeast in anative from. DNA vaccines present many advantages over protein ones.
      Firstly, the antigenic proteins synthesised within the host cell possess an
      appropriate molecular structure and undergo a post-translational modifications
      specific for a native protein. The next advantage of DNA vaccines is that DNA is
      easier to handle and more resistant than proteins to temperature changes. DNA
      vaccines are likely to induce novel mechanisms of immune response, which may be
      beneficial in case of parasitic invasions. Costs of DNA vaccines are comparable,
      and may be even lower, in comparison to recombinant protein vaccines. The main
      obstacle preventing the use of DNA vaccines is still lack of the complete
      knowledge concerning mechanisms of their action. Vaccines based on transgenic
      plants (=edible vaccines), expressing the protective parasitic antigens, present
      another promising approach in research on anti-parasitic vaccines. Such vaccines
      may be of special importance in prevention of infections with gastrointestinal
      parasites.

PMID- 16886351
TI  - [Resistance to intestinal opportunistic infections using Cryptosporidium sp. as
      an example].
AB  - Cryptosporidium sp. has emerged as an important cause of intestinal opportunistic
      infections in immunocompromised humans, especially in HIV positive patients. The
      host immune responses to these infections both in humans and in animals are still
      poorly understood. However, experimental and clinical studies show that both
      humoral and cellular immune responses are essential to control the duration and
      severity of Cryptosporidium sp. infection. The role of specific IgM, IgG, IgA and
      secretory IgA remains unclear. Nevertheless, high level of IgG and IgM responses
      was found in ADIS patients with chronic infection. Hyperimmune bovine colostrum
      decreases parasite burden and severe diarrhea. Severe chronic infections have
      been found in hosts with selective T-cell deficiency, especially AIDS patients
      with low CD4+ T-cell counts (<50 cells/mm3). Moreover, it is also generally
      agreed that T lymphocytes are required for the resolution of both acute and
      chronic cryptosporidisis. Several studies suggest that IFN-gamma is very
      important in the control of Cryptosporidium infection; especially intestinal
      intraepithelial CD4+ T-cells (IEL) that produce IFN-gamma are potentially crucial
      mediators of host immunity to Cryptosporidium. Recent experimental studies also
      indicate that mice deficient in either alphabeta or gammasigma T cells are more
      susceptible to infection than control mice, however gammasigma T-cells have a
      less critical role than alphabeta T-cells. Less extensive studies investigating
      the role of other cells and cytokines both in the innate and cell-mediated immune
      responses to Cryptosporidium sp. are also discussed.

PMID- 16886352
TI  - [Strongyloidosis. Part VI animal models].
AB  - Animal models (rat, mouse, dog and monkey) being used in comparative
      investigations on immunobiology, pathology, clinical manifestations and treatment
      ot human atrongyloidosis were presented.

PMID- 16886353
TI  - [Helminth fauna of free living European bison Bison bonasus (L.) in Bieszczady
      Mountains (Karpatian Mountains, Poland)].
AB  - Four free living European bison from Bialowieza/Caucasus line shot in February
      1997 within Lutowiska Forestry District in the Bieszczady Mountains were used in
      investigations. All examined animals were infected with helminths. There were
      found 10 species of parasites. Five species of them Ostertagia leptospicularis,
      O. kolchida, Spiculopteragia boehmi, Cooperia pectinata and Ashworthius sidemi
      are thypical parasites of Cervides, and from them were infected bison in
      Bieszczady. In all necropsied animals was found invasion of nematode A. sidemi,
      with mean intensity 1542 specimens. It is the first registration of A. sidemi in
      Poland and European bison is a new host for this parasite. It seems that the
      source of infection A. sidemi in European bison in Bieszczady is the local
      population of deer, which during their migrations could bring this parasite from
      neighbouring Ukraine and Slovakia, where this nematode have been introduced
      together with deer Cervus nippon. There are also presented results of coproscopic
      examinations of 17 fecal samples from free living European bison in Bieszczady.

PMID- 16886354
TI  - [Helminths fauna of fishes in the Mala Panew river drainage basin].
AB  - A parasitological investigation was made at 420 fishes from 10 species: Perca
      fluviatilis L., Gymnocephalus cernuus (L.), Gobio gobio (L.), Tinca tinca (L.),
      Leuciscus idus (L), Noemacheilus barbatulus (L.), Lota lota (L.), Leucaspisus
      delineatus (HECKELL 843), Blicca biorkna (L.) and Rhodeus sericeus amarus (BLOCH
      1782). The fishes were caught over one year period (1995-1996) in the Mala Panew
      river drainage basin (South Poland). In examined fishes the following parasite
      species were found: Diplostomum spathaceum (RUDOLPHI 1819)--metacercaria;
      Tylodelphys podicipina KOZICKA et NIEWIADOMSKA, 1960--metacercaria,
      Asymphyllodora tincae (MODER 1790); Bunodera luciopercae (MULLER 1776);
      Triaenophorus nodulosus (PALLAS 1781)--plerocercoid; Proteocephalus cernue
      (GMELIN 1790); Camallanus lacustris (ZOEGA 1776); Neoechinorhynchus rutili
      (MULLER 1780); Echinorhynchus borealis (LINSTOW 1901); Acanthocephalus lucii
      (MULLER 1776) and Pomphorhynchus laevis (MULLER 1776). One species of tapeworm:
      P. cernue appeared as a new in the parasitefauna of Poland.

PMID- 16886355
TI  - [Analyses of the population structures of Mallophaga infesting urban pigeons].
AB  - A total of 70 pigeons from Cracow area was examined and the representation of
      bird lice (Mallophaga) infesting them estimated. Mostly the populations of two
      dominant species: Columbicola columbae columbae (L.) and Campanulotes bidentatus
      compar (Burm.) were assessed. 47% of birds inspected had less than 100 specimens
      of Mallophaga, although the highest infested one had 900 specimens. Sex and age
      of pigeons did not influence the number of bird lice present, and only weak
      health condition of individuals allowed higher infestation. The sex structure of
      ectoparasites was balanced, with a slightly higher number of females during the
      year of study. The highest number of bird lice was detected in autunm and the
      larvae definitely predominated then, as well. Similar tendency was observed in C.
      c. columbae populations. The course of age dynamic of C. b. compar was somewhat
      different, having the peak in July, and the imago stage dominated in this
      species. The populations of in C. c. columbae showed developmental signs, whereas
      the population structures of C. b. compar gave evidence of their regression.

PMID- 16886356
TI  - Occurrence of Strongylidae (Nematoda: Strongyloidea) in Polish horses "tarpans"
      from Popielne Reserve.
AB  - The study was performed to evaluate intensity of strongylid infection in stabled
      tarpans using the method of collecting worms after anthelmintic treatment and in
      wild tarpans from Popielne reserve on the basis of faecal examination. After
      treatment with ivermectin 12 cyathostomes and one large strongyle species were
      recovered from the faeces of two tarpans. The most abundant cyathostome species
      were C. catinatum, C. pateratum, C. longibursatum, C. nassatum and C. coronatus.
      A higher intensity of infections with small strongyles (cyathostomes) was found
      in stabled group than in the group from the reserve. Large strongyles were more
      prevalent in wild tarpans, with Strongylus vulgaris as most common species
      (66.7%), but the intensity of infection was low. The present results are compared
      with earlier studies of horses in Poland and other countries. The results confirm
      the stability of cyathostomes in different breed of horses over the world.

PMID- 16886357
TI  - [Isolation of Borrelia burgdorferi sensu lato in ticks Ixodes ricinus by
      polymerase chain reaction (PCR)].
AB  - Attempts were made to identify the causative orgamsm of Lyme disease in Szczecin
      from tick Ixodes ricinus as a vector. Ticks were collected in 1997 year in forest
      areas of Szczecin, from localites associated with numerous attendance of people.
      The method used in this study was the polymerase chain reaction (PCR) on the
      flagellin structural gene fla of Borrelia burgdorferi sensu stricto. The
      flagellin PCR primer set reaction was conservative for B. burgdorferi sensu
      stricto, B. afzelii and B. garinii. The overall prevalence of B. burgdorferi
      sensu lato, in tick population studied was 8.8%. The female, nymphs and larves of
      Ixodes ricinus were infected almost just the some--about 10%, when the male 2.5%
      only.

PMID- 16886358
TI  - [Parasites leech Batracobdelloides moogi (Nesemann & Csanyi, 1995) (Hirudinea,
      Glossiphoniidae vaillant, 1850) of Polish fauna?].
AB  - In the light of recent studies (NESEMANN and CSANYI 1995) on the genus
      Batracobdella (VIRGUIER 1879) Batracobdella paludosa (CARENA 1824)--a component
      of the Polish fauna--is actually Batracobdelloides moogi (NESEMANN and CSANYI
      1995).

PMID- 16886359
TI  - [Soil contamination with Toxocara spp. eggs in the Krakow area and two nearby
      villages].
AB  - The distribution of Toxocara spp. eggs was studied in the Krakow city and nearby
      villages Grodkowice and Lazkowice. In Krakow out of 80 samples surveyed 30% were
      positive and the mean egg density was 3.7 eggs/100g soil. Court-yards and squares
      in the centre of the city were the most heavily contaminated areas (58% samples
      positive). In two nearby villages Toxocara spp. eggs were present in 16% samples
      examined and the mean egg density was 0.8 eggs/100g soil. Almost 90% of Toxocara
      spp. eggs recovered were infective. At least 80% of the eggs were classified as
      T. cati by egg's morfology.

PMID- 16886360
TI  - The phenomenon of apoptosis in the course of experimental trichinellosis in mice.
AB  - Mice infected with 200 Trichinella spiralis larvae were killed at 3-69 days post
      infection (dpi) and the jejunum and masseter muscles were sectioned in a cryostat
      and examined in the Tunell method with "In situ Cell Detected Kid POD" of
      Boehringer-Mannheim. Data concering the exact localization and dynamic of apoptic
      cells in both organs are presented. The authors conclude that apoptosis plays a
      important role in the pathogenesis of trichinellosis.

PMID- 16886361
TI  - [Hydatoid cysts of liver--diagnostic and therapeutic problem].
AB  - In the Department of General Surgery of Medical University 11 patients with
      hydatid cysts of liver were operated. Ultrasonography and computer tomography
      allowed to define exact localization, size and contents of the cysts, what made
      possible planning of operating procedure. In 2 cases nonanatomic resection of
      liver parenchyma was performed, in 2 ones with coexisting stomach neoplasm just
      excision of the frontal wall of the cyst and emptying of the interior. In all the
      other cases the cysts were removed with surrounding liver tissue. Late results of
      surgical treatment with albendazol therapy are good. Diagnosis of echinococcic
      desease should be precised, considering with possibility of co-existing foci in
      other organs.

PMID- 16886362
TI  - [Leeches (Hirudinea: Piscicolidae and Glossiphonidae) infecting lake fish in the
      Ukiel, Warniak and Wulpinskie. Preliminary study].
AB  - The aim of the study was to determine leeches found on the lake fishes. From the
      lake Ukiel, 213 roaches (R. rutilus) and from the lake Wulpinskie 202 were
      examined between Nov. 1988 and Dec. 1999. From the Warniak 258 roaches and 9
      tenches (Tinca tinca) were examined between May 1998 and Nov. 1999. Warniak on
      roach (R. rutilus) 4 Piscicola geometra and Hemiclepis marginata on the fish body
      were found, tench (Tinca tinca) P. geometra were found on gills. Ukiel on roach
      Piscicola pojmanskae on gills were found. Wulpinskie on roach P. pojmanskae and
      Piscicola sp. as well as 2 Caspiobdella fadejewi on gills were found. Prevalence
      and intensity of fish infection with leeches was low in all lakes. C. fadejewi
      and P. pojmanskae are the first recorded on the lake fishes. Further
      investigations are necessary since they can result in informations concerning
      inhabitation of new microhabitants with P. geometra gills.

PMID- 16886363
TI  - Efficacy of mebendazole in treatment of selected parasitoses--a retrospective
      study.
AB  - The efficacy of mebendazole was evaluated as a result of six-year experience in
      the treatment of patients of Outpatients Clinic and Clinic of Infectious,
      Parasitic and Tropical Diseases in Lodz. The treatment covered 6132 subjects
      infected with: Ascaris lumbricoides, Ancylostoma duodenale, Trichiuris trichiura,
      Enterobius vermicularis and Echinococcus granulosus. Nematode infections were
      diagnosed by coproscopic methods whereas echinococcosis with serologic tests and
      ultrasonographic examination of abdominal cavity. Mebendazole was administered in
      the dose of 200 mg per day: for 3 days in ascariasis, for 5 days in A. duodenale,
      T. trichiura and mixed infections. In enterobiosis was applied a pulsation
      therapy: 200 mg a day for 3 days, a week of break (three subsequent cycles). In
      echinococcosis the drug was administered in the daily dose of 600 mg for 30 days.
      Follow-up examinations were carried out 30, 60, 120 and 160 days after the
      treatment. In the case of ineffectiveness of the first course, the treatment was
      repeated. The efficacy of the therapy was as follows: ascariasis 97.1%, A.
      duodenale infection 100%, trichuriasis 92.1%, enterobiosis 93.3 %, mixed
      infections 95.3%, echinococcosis 77.2%. No side effects were observed.

PMID- 16886364
TI  - [Some aspects of the immune response of Polish Wrzosowka sheep against
      gastrointestinal nematodes infection].
AB  - The paper presents different aspects of natural gastrointestinal nematode
      infection in this primitive, prolific Polish Wrzosowka breed of sheep. The study
      was carried out on the flock located at the farm run by Warsaw Agricultural
      University at Zelazna (central Poland) in 1995-1998. Egg counts per gram of
      faeces, larval differentiation, total white blood cell counts, blood eosinophil
      counts, interleukin-5 concentration, lymphocyte blastogenic activity and IgG
      immune response were discussed. The egg counts were overdispersed and followed a
      different pattern each grazing season. The larvae obtained from faecal culture
      belonged to 6 categories: Trichostrongylus spp., Haemonchus contortus,
      Teladorsagia spp., Cooperia spp., Chabertia ovina/Oesophagostomum spp. and
      Nematodirus spp. However there were no discernible patterns in the composition of
      nematode population over time. Data analyses have shown that egg counts,
      eosinophil counts, IL-5 concentration and IgG level in different months each year
      were repeatable. The results obtained in two divergent groups of sheep, chosen
      for consistently low or high faecal egg counts have been presented also. Polish
      Wrzosowka breed of sheep is under conservation breeding program based mainly on
      the markers of breed standard. The results obtained in this study revealed that
      some parasitological, haematological and immunological parameters should be added
      to this program.

PMID- 16886365
TI  - [Serotonin metabolism in children infected with Giardia intestinalis].
AB  - According to the data from the last 4 years, 3.8% of all diagnosed parasitoses
      are giardiases. During 5 years Giardia intestinalis was found in 24 children
      hospitalized in the General Hospital of the Wroclaw Voivodship: in 14 girls and
      10 boys, 2-12 years old. The parasite was identified coproscopically and on the
      basis of clinical symptoms. Before the medication, the blood was taken from each
      child to determine the serotonin level and the (MAO) monoaminooxydaze, enzyme
      metabolizing serotonin acivity in the blood serum. The results were compared to
      the values obtained in the control group of 10 healthy children, 3-12 years old.
      III children were divided into two groups: first consisted of 12 children, 2-5
      years old, second--of 12 children, 6-12 years old. In the first group 210%
      increase of the serotonin level in the blood and slight 32,4% increase of the MAO
      activity were observed in comparison with the control group. In the second group
      the serotonin level in the blood increased 221% in comparison with the control,
      while the MAO actmty increased 45.1%. In older children marced clinical symptoms
      could be observed, mainly malfunction of the alimentary tract, microelements
      shortage and anemia. The highest level of serotonin and MAO activity was found in
      the child with bile duct irritation. The reason for the increased level of
      serotonin and MAO activity can be pathogenic action of parasite's trophozoites
      and cysts on the jejunum mucosa and mobilization, proliferation and degranulation
      of tissue mastocytes. Serotonin, released from mastocytes, can be the cause of
      enhanced peristalsis and mucosa congestion.

PMID- 16886367
TI  - [Parasitic Acari of wild boar (Sus scrofa L.) from Pomerania lake district].
AB  - In years 1994-1998, 553 Wild Boars (Sus scrofa L.) were examined in the area of
      north-western part of Poland. Four species of parasitic acarids were found:
      Demodex phylloides, Sarcoptes scabiei, Dermacentor reticulatus and Ixodes
      ricinus. The highest infestation was observed in the case of D. phylloides (30%),
      the next from the top was presented by Ixodes ricinus (17%). S. scabiei and D.
      reticulatus occured seldom.

PMID- 16886366
TI  - [The susceptibility of Aspergillus and Penicillium to recent antimycotics].
AB  - Fifty four mould strains (32 Aspergillus and 22 Penicillium) isolated from
      clinical materials were tested using dilution method. Two test media were used:
      Yeast Nitrogen Base (YNB) and Czapek Dox (CD). The following drugs were tested:
      amorolfine, cyclopirox, itraconazole, and terbinafine. In the dilution method,
      the drugs were tested at four contrentrations: 0.1 mg/l, 1 mg/l, 10 mg/l, and 100
      mg/l. No matter which medium and/or drug was used, terbinafine turned out to be
      most effective. The drug at a conceatration of 1 mg/l inhibited 88.9% of the
      strains in the CD medium. The MIC values in the YNB medium varied from 0.1 mg/l
      through 100 mg/l, however, 50% of the strains were inhibited at 1 mg/l or less.
      Itraconazole revealed a fairly good in vitro antifungal action, particularly in
      the CD medium: 77.8% of the strains were inhibited at 10 mg/l or less.
      Aspergillus fumigatus and Aspergillus flavus were most susceptible to
      itraconazole. The MIC values of cyclopirox amounted to 100 mg/l for all of the
      strains in the CD medium but not in the YNB where they varied from 1 mg/l to 100
      mg/l. Amorolfine was the least effective drug. Most of the strains were inhibited
      at a concentration of at least 100 mg/l. The findings give evidence that the
      susceptibility of Aspergillus and Penicillium to the particular drugs is
      different, and that the results are influenced by the test medium.

PMID- 16886368
TI  - [Source and significance of genetic polymorphism of selected parasitic protozoa].
AB  - The application of biochemical and molecular techniques in parasitological
      studies has provided increasing evidences of genetic polymorphism among parasite
      populations. This review presents possible origins of genetic variation within
      populations of various protozoan species. Since the mode of reproduction has an
      important influence on genetic polymorphism within parasite populations these
      considerations refer mainly to some protozoan parasites which have various life
      cycles, e.g. Giardia, Trypanosoma, Cryptosporidium, Toxoplasma. Also other
      factors associated with parasites (such as: transmission and passage history in
      laboratory conditions; occurrence in different hosts or geographic regions;
      selective pressure of drugs; competitive interactions between populations) that
      affect parasite genetic diversity are discussed. However, the number of examined
      isolates of parasites and genetic markers, assortment of methods, probes, primers
      and reagents used is also of significance. The significance of genetic
      variability in parasite populations is still the subject of much interest and
      controversy. A simple interpretation of such variation is impossible because of
      the complexity of host-parasite interactions. The knowledge of parasite diversity
      at the nucleic acids level has continually increased, but a corect interpretation
      of this phenomenon requires at least the same knowledge of genetic variability in
      host populations. Nevertheless, genetic variability in protozoan parasites has
      many important implications, e.g. for taxonomy, epidemiology, control and
      evolution. Genetic differences within parasite populations might also be
      associated with phenotypic variability, e.g. virulence, antigenicity,
      infectivity, drug sensitivity, host preference etc.

PMID- 16886369
TI  - [Role of blood platelets in parasitic diseases].
AB  - Blood platelet are of crucial importance in hemostasis. Little attention has been
      paid to their bacteriocidal activity and their potential role in parasitic
      infections. Activation of blood platelets may result from direct contact with a
      parasite or IgE, IgG, complement factors, lymphokines, CRP. Blood platelets
      reveale cytotoxic activity through release various inflamatory mediators,
      phagocitic activity and cooperation with other cells of immunologic system. The
      precise mechanism of all platelet cytotoxic effects remains unclear.

PMID- 16886370
TI  - [The report on session "drugs and diagnostic" organized on 11 September 1998 in
      Olsztyn by Polish Society of Parasitology].

PMID- 16886372
TI  - [Fish parasites and parasitoses].

PMID- 16886371
TI  - [The influence of diptera on the domestic animals].
AB  - The Diptera attacked domestic animals in Poland are: Simuliidae, Culicidae,
      Tabanidae, Gasterophilidae, Hypoder-matidae and Muscidae. The insect assail the
      crazing animals, mostly during sunny day dna at close of day. Lack of effective
      repelents and also difficulties with their usage, makes it impossible to complete
      extermination of parasitic insects in the environment. It is posible to
      effectively fight against Hypoderma bovis and Gasterophilus spp.

PMID- 16886373
TI  - Fishes as definitive or intermediate hosts of Opisthorchioid trematodes in South
      America.

PMID- 16886374
TI  - [The role of eye-like spots of parasitic leeches (Hirudinea, Piscicolidae) in
      searching for fish-hosts].
AB  - Piscicola geometra (L.), Piscicola respirans Troschel, 1850, and Caspiobdella
      fadejewi (Epshtein, 1968) find their hosts (fishes) by reacting to their shadow.
      Eye-like spots whose number ranges from 8 to 16 depending on a species, located
      on the posterior sucker are the main receptors perceiving the decrease in light
      intensity and thus enabling an immedaite reaction to the host's shadow. They are
      distributed on the perimeter of the sucker, are absent only from the section that
      is constantly shaded by the leech body. Experiments with a simulated shadow
      reveled considerable differences in the threshold light doses between the studied
      species: P. geometra - 12 lux, P. resprans - 4 lux and C. fadejewi - 2.5 lux.
      Below these values the leeches do not perceive the decrease in light intensity
      and do not make host-searching movements. The smallest decreases in light
      intensity, at which the leeches still make host-searching movement, are: P.
      geometra - 5 lux, P. resprans - 2 lux, and C. fadejewi- 1.5 lux. In case of P.
      respirans and C. fadejewi such small decreases in light intensity (2 - 1.5 lux)
      may be caused only by small fishes which, according to the results of the
      experiment, should not be infested. This is confirmed by field observations -
      small fishes are mostly free from parasites. Large fishes (casting a large
      shadow) have much more numerous leeches.

PMID- 16886376
TI  - [Enterobiosis in kindergarden and school children from selected institutions from
      Olsztyn and surroundings].
AB  - The studies were conducted during the school year of 1996/1997 among the children
      at the age of 5, 6 and 7 years old from Olsztyn and nearby municipality of Purda.
      In total, 151 children were examined by Graham's method. The presence of eggs of
      the parasite was confirmed in 13.3% of the total examined population. The
      infestation was lower in Olsztyn (12.0%) and the lowest in Purda (9.4%) but in
      the former state-owned Farm village Prajlowo it reached 27.8%. In general, the
      pinworms were found more frequently in 7 year old children (23.33%) than in case
      of the others (8.69% and 7.14% for 5 and 6 year old children respectively). In
      the study, younger boys were more frequently infested than the girls.

PMID- 16886375
TI  - [Occurrence of metacerkariae Diplostomum sp. in the Siberian turgeon fry
      (Acipenser baeri Brandt)--preliminary study].
AB  - Siberian sturgeon fry coming from three different ponds has been examined. 1.
      "Dgal" - fish culture conerete-terrestrial pond beloning to D.O.Z. Dgal Inland
      Fisheries Institute in Olsztyn supplied with fresh water from Great Dgal Lake; 2.
      "Grzmieca" - fish culture pond terrestrial, natural belonging to fishing farm
      Grzmieca near Brodnica; 3. "Konin" - fish culture pond near Konin supplied with
      water utilized by near heat and power generating plant. Total of 80 sturgeons fry
      with parameters: length 17.5 cm - 38.5 cm, weight 21 g - 134 g, age 0+1+ has been
      examined. The examinated group of sturgenos had metacercariae Diplostomum sp. in
      their lenses. Prevalence of infection of sturgeon with metacercariae Diplostomum
      sp. was high in all this three ponds. Intensity of infection was also high in
      ponds "Dgal" and "Grzmieca", but low in "Konin". In ponds "Dgal" and "Konin" we
      have obtained high positive correlation ("Dgal" - r = 0,606, p < 0,05; "Konin" -
      r = 0,743, p < or = 0,01) between number of metacercariae in sturgeon and
      temperature of water. Our study confirmed observations other authors
      susceptibility sturgeon fry on the Diplostomum sp. invasion.

PMID- 16886377
TI  - [Economic losses in pheasant breeding evoked with endoparasites].
AB  - Parasitical invasions constitute a serious veterinary-economic problem in
      pheasant breeding. The studies were carried out between 1995-1997 in a big
      breeding centre situated in the Middle Pomerania region, where the basic flock
      amounted to 1000-1200 bird individuals. The aim of the study was to determine a
      condition of the pheasants' affliction with nematodes, reasons for the invasion
      and possibilities of a decrease in the losses thus brought about. In the
      subsequent years, the flock affliction reached the following proportions: 40% in
      1995, 42% in 1996, and 68% in 1997. Between 1995 and 1996, the findings revealed
      eggs of the nematode Capillaria sp (C. anatis and C. phasianina) in their faeces,
      with less frequent cases of Trichostrongylus tenuis, Heterakis isolonche and
      Syngamus trachea. Between 1995-1996 40% deaths in the afflicted flock were
      brought about by Syngamus trachea whilst in 1997 syngamosis resulted in 80%
      deaths among the afflicted birds. To determine reasons for the confirmed nematode
      invasion in the studied period during which all the requirements were fulfilled
      in the pheasant breeding, conclusions were drawn on the basis of the study. Also,
      preventive measures were suggested to stop any further appearance of syngamosis
      or losses due to other endoparasites, as those in 1997.

PMID- 16886378
TI  - [Epidemiological studies on Echinococcus multilocularis in red foxes in north
      west Poland].
AB  - The studies were carried out in 15 provinces of North-West part of Poland in the
      years 1994 - 1997 under a regime of strict laboratory safety regulation. The
      intestine of 1909 red foxes were examined for the presence of Echinococcus
      multilocularis according to the method of Eckert et al (1991). The intestines
      were divided finto four to six sections and fifteen smears were prepared from
      each animal under study. Foxes infected with E. multilocularis were detected in 8
      provinces. The average prevalence rate in these provinces was 1.20 per cent. Of
      special interest fis the finding in Slupsk and Gdafisk regions, where 9.6 per
      cent of foxes were infected with E. multilocularis. In comparison with some other
      European endemic regions the prevalence rates of E. multilocularis in Poland was
      low, except for the Stupsk-Gdansk area.

PMID- 16886379
TI  - [Risk of tick-borne encephalitis (TBE) virus infection among people
      occupationally exposed to tick bites].
AB  - The paper presents the results of seroepidemiologic studies concerning tick-borne
      encephalitis (TBE) in 1583 persons (1261 forestry workers and 233 farmers) from
      the Lublin region (eastern Poland) occupationally exposed to ticks and in 130
      healthy blond donors (a control group). The mean percentage of seropositive
      reactions in forestry workers amounted 19.8% and in farmers 32.0%. Based on 5
      year research (1994-1998) conducted in 5 districts of the Lublin region, an
      existence of endemic foci of TBE was detected in the district of Biala Podlaska,
      on the areas of Radzyn Podlaski and Parczew, where the percentage of seropositive
      reactions in forestry workers exceeded 50%. Statistical analysis showed that the
      frequency of seropositive reactions in forestry workers and farmers was
      significantly greater compared to control group (p<0.001 and p<0.05,
      respectively). It indicates that these groups are occupationally exposed to TBE
      wirus. Totally, in the years 1994-98 nine clinical cases of TBE (acute
      neuroinfection) in forestry workers and fourteen clinical cases in farmers were
      confirmed serologically. The effectiveness of specific immunization against TBE
      was proved on the brie of 100% seroconversion in 56 earlier seronegative forestry
      workers. The obtained results proved that forestry workers and farmers in Poland
      are under increased risk of infection with TBE virus.

PMID- 16886380
TI  - [Own clinical observations of toxocara infections].
AB  - Toxocarosis clinical forms wers diagnosed according to Kraus et. al. (1995).
      There were three forms: 1) asymptomatic - marked by hypereosynophilia and ELISA
      positive serologic reaction, 2) minor - with cutaneous, pulmomary and
      pseudorheumatic lesions, 3) major - with hepatosplenomegaly and multifocal
      inflammatory lesions of organ of sight. Over the years of 1994-1997 in
      Infectious, Parasitic and Tropical Diseases clinic of the Voivodship Specialist
      Hospital of Lodz we found and treated 137 Toxocara canis cases. Among them 63
      (46:0%) asymptomatic, 57 (42.6%) minor and 17 (12.4%) major forms were diagnosed.
      The disease was detected in 80 (58.4%) adults and 57 (41.6%) children. Seventy
      six patients lived in towns and 61 in country. Minor form patients had the
      symptoms as follows: skin allergy, large joints lesions, augmentation in lymph
      nodes. Radiology examinations revealed pulmonary lesions. Using ultrasonography
      there was found hepatosplenomegaly and changes echogenity in patients with major
      form. Biochemical tests showed elevation in hepatic enzymes activity. Lesions of
      organ of sight were multifocal and usually included uveitis, retinitis,
      inflammation of anterior chamber and inflammation of vitreous body.

PMID- 16886381
TI  - [The time of maintainance of positive serologic results among patients operated
      on echinococcal liver cysts].
AB  - The purpose of this work was to analyse results of serologie examinations and
      complaints reported by patients who were operated on echinococcal liver cysts.
      The analysis was conducted on patients who were qualified to surgical removal of
      echionococcal liver cysts. Persons who were analysed answered the questionaires
      and 11 of them send sera for serologie examination. The questionaires consisted
      of questions about time since operation, complaints before and after operation
      abdomen pains, distensions, vomits, exanthema, weakness, headaches). Results
      showed that patient were from 1 to 6 years after operation. Among 11 who send
      sera 18% results were negative (2 and 6 years after operation) and 82% was
      positive. Analysis of 15 questionnaires showed that majority of patients still
      had the complaints that were present before operation.

PMID- 16886382
TI  - [Studies on the incidence of echinococcus multilocularis in red foxes (Vulpes
      vulpes) in north-east, central and south of Poland].
AB  - During the year 1994-1997, a total number of 1042 red foxes orginating from the
      33 provinces North-East, Central and South of Poland under special safety
      procautions for intestinal stages of Echinococcus multilocularis using the
      mucosal-smer technique were examined. An average of 5.09% (53 foxes) from 10
      provinces was infected. In those provinces, the prevalance varied between 1.19%
      to 35.71%. The infection varied from low to very high but mostly harboured gravid
      E. multilocularis parasites with thick-shelled eggs. Our data indicate that E.
      multilocularis in foxes has a surprisingly wide distribution in Poland. These new
      epidemiological data indicate that a potential risk of infection for humans may
      exists in all areas where foxes infected with E. multilocularis have been
      identified. It has been assumed that E. multilocularis might also occur in other
      provinces in which foxes examination have not yet been undertaken or number
      examined of animals was low. This study was supported by a two grands from the
      Swiss National Foundation (projects No 7PLPJ038414 and 7PLPJ041302).

PMID- 16886383
TI  - [Dermatophyte infections in persons returning from the tropics].
AB  - Over the years 1996-1997 mycological examination were performed in 367 persons
      with cutaneous lesions, returning from the tropics. Fungal infection was
      diagnosed in 141 patients. Twenty nine (42.65%) of the cases were of single
      focal, 32 (47.06%) of bifocal and 7 (10.29%) of multifocal nature. One hundred
      forty one isolates included 50 (35.6%) moulds 23 (16.3%) yeast - like fangi and
      68 (48.1%) dermatophytes. Genus classification of the dermatophytes was as
      follows: Microsporum - 16 (23.5%), Epidermophyton - 15 (22.1%), Trichophyton - 37
      (54.4%). Over the years 1996-1997 the following dermatophyte species were
      isolated: M. audouini, M. ferrugineum, M. canis, T. rubrum, T. mentagrophytes
      var. granulosum, T. tonsurans, T. violaceum, E. floccosum. Microsporum genus was
      isolated from persons returning from East, West and Central Africa, and from
      South Europe, Trichophyton genus was isolated from persons returning from Asia
      and South America.

PMID- 16886384
TI  - [Toxoplasmosis of the brain as an example of the opportunistic invasion of the
      women HIV positive].
AB  - Most toxoplasmosis infections occur in the brain. Cerebral toxoplasmosis is a
      specially serious complication in patients with AIDS. Similarly to other
      opportunistic pathogens, Toxoplasma gondii causes rapidly progressive, and often
      fatal disease in immunosuppressed patients. The diagnosis is difficult, since no
      sensitive and specific non-invasive diagnostic tests exist. The subject of our
      study is a 27-old female initially diagnosed with metastasis in central nervous
      system.

PMID- 16886385
TI  - [The molecular diagnosis of Pneumocystis carinii in the light of a new biological
      and epidemiological data].
AB  - A new data from investigations on Pneumocystis carinii were presented as well as
      an application of molecular techniques to the diagnosis of P. carinii pneumonia.

PMID- 16886386
TI  - [Immune polypeptides activity in bee hemolymph].
AB  - The honeybee developed through evolution efficient inborn and acquired immune
      mechanisms which allow it to function in the enviromment. In the inborn immunity
      phagocytosis is classified to the oldest defensive mechanisms which relies on
      catching and destruction of the pathogens by the plastmocytes and granulocytes in
      the hemolymph and lysozymes - the most important components of the natural
      humoral immunity. Acquired immunity covers, above all, polypeptides and immune
      proteins e. g. apidaecin and abbacin. Apidaecins represent one of the most
      important anti-bacterial elements of acquired immunity. Apidaecins arise from fat
      bodies appearing soon after bacterial infection, also protect the insect from
      envirommental pathogens. Abaccin acts mainly on Gram positive bacteria. Its
      characteristic quality is delayed action in camparision to apidaecins, synergy
      with bee hemolymph anti-bacterial factors as well as assistance in anti-bacterial
      defense.

PMID- 16886387
TI  - [Catfish (Ictalurus nebulosus L.) a new host of Schulmanela petruschewskii
      (Shulman, 1948) (Nematoda, capillariidae) in Poland].
AB  - This paper contains the second record and locality of S. petruschewskii in
      Poland. This nematode was found on the catfish (Ictalurus nebulosus L.) from the
      Odra River in Wroclaw (Lower Silesia). S. petruschewskii have been described only
      in Gymnocephalus cemuus from the Szczecin Firth until now. The authors gave the
      illustrations (with dimensions) of this species, according to the material from
      the catfish.

PMID- 16886388
TI  - [Scientific Life. Slovak Republic and Czech Republic Days of Parasitology].

PMID- 16886389
TI  - Blood leukocyte responses in rats vaccinated with cDNA encoding glutathioinie-S
      transferase of Fasciola hepatica.
AB  - Changes in blood leucocyte levels were investigated in Spraque-Dowley rats
      vaccinated with cDNA or protein of glutathione S-transferase (GST) of F. hepatica
      and subsequently challenged with metacercariae of the liver fluke. The analysis
      of the leucocyte responses measured in vaccinated rats suggests that the form of
      antigen used for vaccination influenced dynamics of white blood cell response to
      the fluke infection. The most clear differences were observed in neutrophil and
      eosinophil levels. The weakest reaction of these cells to the challenge infection
      was observed in rats vaccinated twice with cDNA. In contrast, in rats which
      received the first antigen dose as cDNA and the second vaccination with GST
      protein, both neutrophil and eosinophil responses were much higher, especially at
      5 and 9 WAI.

PMID- 16886390
TI  - Host--protozoans--bacteria--fungi interrelations in the mouths of patients with
      systemic illnesses.
AB  - The aim of this work was to study clinical changes and microorganisms in mouths
      of three patient groups: with congenital disorders (Cd), dialyzed (D) and control
      (C). Fifty five patients, 20 to 62 years old were assessed. Swabs and samples of
      periodontal tissue were used for microscopical study to detect of protozoans and
      for bacterial and fungal cultures. E. gingivalis and T. tenax were found in all
      groups. Three out of Cd patients were infected with Acanthamoeba sp.. Fecal
      bacteria were more often found in D than Cd. In all 30-40 years old D patients,
      fecal bacteria and various strains of C. albicans occurred. We found that
      systemic diseases favour instabilities in mouths changing interrelations between
      protozoa, bacteria and fungi. It may increase risk of clinical complications.

PMID- 16886391
TI  - [New imaging diagnostics of liver echinococcosis].
AB  - Cystic and alveolar echinococcosis, parasitic diseases, caused in humans by the
      larval stage of tapeworm Echinococcus granulosus and E. multilocularis are rare
      diseases in Poland. We have diagnosed 71 patients with cystic echinococcosis and
      10 patients with alveolar echinococcosis during last 12 years. Echinococcosis
      still create significant diagnostic difficulties, particularly alveolar one.
      Progress and actually available radiological imaging techniques, which can be
      applied in the cystic and alveolar echinococcosis diagnostics, are presented.
      Ultrasound appearance, CT, MRI images are described. Own experience with Proton
      Magnetic Resonans Spectroscopy in two patients with recurrent alveolar
      echinococcosis are presented.

PMID- 16886392
TI  - [Cytoadherence in cerebral malaria as particular example of pathology in host-
      parasite system].
AB  - Cerebral malaria in man and in animals is the consequence of a cascade of events,
      involving the patological changes, leading to the amplification of the expression
      of the receptors for cytoadherence on brain capillary endothelial cells.
      Sequestration is the process by which erytrocytes infected with the mature forms
      of the malaria parasite Plasmodium falciparum disappear from circulation and
      accumulate within venules and capillaries of various organs and tissues. The
      molecular mechanism in sequestration is one of the most rapidly advancing fields
      in malaria research. The several specific aspects considered in this paper. Our
      electron micrographs show cytoadherence in own model of cerebral malaria in rats
      infected with Plasmodium berghei.

PMID- 16886393
TI  - [Frequency of antibodies against Trichinella spiralis and Echinococcus ssp.
      appearance in children with atopic diseases].
AB  - Parasitic infestation and atopic diseases have common features. The aim of our
      study was to evaluate the occurrence of Trichinella and Echinococcus
      seropositivity in children with atopic diseases. The study group involved 72
      children aged from 2,5 to 18 years with asthma and allergic rhinitis. The control
      group comprised 30 children without allergic diseases. In 12 children with atopic
      diseases the serological tests were positive for Trichinella spiralis, in II for
      Echinococcus spp. and in 5 both for Trichinella and Echinococcus. In control
      group the serological tests were positive in 3, 6 and 3 children respectively.
      There were no differences in occurrence of positive results of serological tests
      in children with atopy and children without allergic diseases.

PMID- 16886394
TI  - Serological investigation in children infected with Ascaris lumbricoides.
AB  - The study included 260 hospitalised children with suspected infection with human
      ascaris. In serological diagnostics a protein antigen obtained from Ascaris
      lumbricoides was used. ELISA method was applied. IgG antibodies were detected.
      Positive results were found in 15% of the examined children. No relation to the
      gender or demographic conditions was found. The most frequently observed symptoms
      in the patients with Ascaris lumbricoides were: abdominal pain--87%, diarrhoea
      15%. In 31% of the cases eosinophilia was found. Scatoscopy was carried out for
      all the patients, using the PARASEPT system and Kato and Miura methods as well as
      decantation and flotation. The examination, which was repeated three times, did
      not show cysts or eggs. Serological investigation exhibits higher sensitivity
      than the traditional methods. Their use in recognising ascariasis in humans
      significantly facilitates diagnostic procedures, especially in the lung phase of
      the disease, the larval stage or in cases of infection with an individual
      parasite, when the faeces samples do not contain the eggs. Serological
      investigation is also useful in all cases of suspected VLM.

PMID- 16886395
TI  - [Experimental toxocariasis in rabbits: immunological markers of ocular
      infections].
AB  - Rabbits were infected with an oral dose of 50 000 eggs of Toxocara canis or with
      an intracarotid injection of the second stage larvae of the parasite in order to
      develop ocular toxocariasis. Serum and ocular fluid samples were collected from
      the rabbits after 1, 3 and 6 months after infection and examined for specific
      toxocaral antibodies and circulating parasite antigen. Furthermore, an
      ophthalmoscopic examination was performed at the time of sampling. None of the
      infected animals showed the signs of ocular involvement, however, toxocaral IgG
      antibodies and circulating parasite antigen were present in the anterior chamber
      fluid samples.

PMID- 16886396
TI  - The mucosal mast cell and IgA plasma cell responses to primary Trichinelia
      spiralis infection in BALB/c mice treated with ketotifen.
AB  - The effect of ketotifen on inflammation in the intestine during T. spiralis
      infection in BALB/c mice was examined. The lack of enteropathy in treated mice
      was accompanied to affected the size of worms and the number of worms, but did
      not prevent the retardation of nematodes in the intestine. Fecundity of females
      in vitro and the number of muscle larvae were not statistically changed after
      treatment. Ketotifen reduced the number of mast cells and IgA plasma cells in the
      intestine. As inflammatory influx, epithelial damage and IgA response are related
      to the action of T cells, ketotifen affected T dependent reactions in the gut of
      T. spiralis infected mice.

PMID- 16886397
TI  - Humoral response in hamsters following vaccination with cDNA encoding acey-1
      cysteine proteinase of Ancylostoma ceylanicum.
AB  - The humoral response in hamsters following vaccination against Ancylostoma
      ceylanicum infections with DNA construct was investigated. Groups of hamsters
      were injected intramuscularly with plasmid pcDNA 3.1. containing cDNA of ACEY-1
      cysteine proteinase. Vaccination resulted in IgG antibody response to somatic
      extracts of adult A. ceylanicum. The highest level of antibodies was observed
      seven weeks after vaccination.

PMID- 16886398
TI  - [Pathogenic fungi with increasing proliferation].
AB  - This paper compared occurrence and intenseness of growth C. glabrata, S.
      capsularis and T. beigelii isolated from sputum, material's bronchoscopic, oral
      cavity, skin and catheters during 10 years observation (1991 - 2000). All
      investigated fungi from 1997 years have been characteristic very distinct rise
      expansiveness appeared in more intenseness of growth and growing rate of replace
      new ontocenoses. Most likely is this consequence successive of decrease immunity
      of man organism about infections yeast - like fungi.

PMID- 16886399
TI  - [The yeast-like fungi infections in medical intensive care patients in years 1996
      - 2000].
AB  - The aim of this study was to analyse, taking into consideration the infection
      risk factors, the incidence of fungal infections occurrence in Medical Intensive
      Care Units. Yeast-like fungi strains isolated from various clinical materials
      underwent mycological examination. Mycological diagnosis was performed in
      compliance with compulsory laboratory methods. The detailed observation concerned
      patients who were admitted to the intensive care unit by urgent reasons or
      because of basic disease aggravation, trauma, surgical operations and those with
      diabetes mellitus. The main etiological fungal infections factor were C. albicans
      strains. The increased incidence of C. glabrata and C. parapsilosis participation
      in yeast-like fungi infection pathogenesis was observed. The results presented in
      this study confirm, that intensive care units patients, for the reason of fungal
      infections, make the increased risk group.

PMID- 16886401
TI  - [Cutaneous mycoses as a problem of the tropics. I. Superficial tropical mycoses].
AB  - Cutaneous mycoses are third among diseases after parasitic and infectious ones
      that pose problems for persons returning from the tropics. The paper presents
      semiotics of the following tropical superficial mycoses: tinea imbricata,
      infections with Scytalidium, tinea nigra, zakazenia grzybami Scytalidium, lupieZ
      czarny, black piedra, white piedra. Treatment, diagnostics and prophylaxis are
      discussed.

PMID- 16886402
TI  - [Cutaneous mycoses as a problem of the tropics. II. Subcutaneous tropical
      mycoses].
AB  - Cutaneous mycoses are third among diseases after parasitic and infectious ones
      that pose problems for persons returning from the tropics. The paper presents
      semiotics of the following tropical subcutaneous mycoses: sporotrichosis,
      chromoblastomycosis, maduromycosis, pheohyphomycosis, zygomycosis and
      lobomycosis.

PMID- 16886400
TI  - [Multifocal colonization and hydrolytic activity of Candida strains isolated from
      lung cancer patients].
AB  - The aim was looking for correlation between hydrolytic activity and multifocal
      Candida invasions in 33 lung cancer patients (LC) before treatment. Materials
      used in this study were pharyngeal and rectal swab, sputum, bronchial secretion
      and urine. Isolation and identification of fungi were performed using ID C 32
      test and the hydrolytic activity using API ZYM test. RESULTS: 1/ there were only
      Candida strains, especially C. albicans (78,8 %) isolated 2/ Candida in more than
      one sample were present in 74%, in three or four in 27,7% of LC. 3/ Candida
      strains produced 17 among 19 investigated enzymes 4/ there were statistically
      significant correlations between the activity of some hydrolytic enzymes and
      number of Candida foci observed. CONCLUSIONS: 1/ the results confirmed the
      influence of Candida hydrolytic activity on the course of infection. 2/
      hydrolytic enzymes activity is one of important Candida pathogenicity factors.

PMID- 16886403
TI  - [Mixed dermatophyte infection in a cat].
AB  - Skin mycoses in animals are mostly caused by Microsporum canis, Microsporum
      persicolor, Microsporum gypseum and in rare cases by Trichophyton mentagrophytes.
      As a rule only one dermatophyte species is isolated from skin lesions, but at
      times mixed infection with bacteria occur. In the described case in a cat with
      typical dermatomycosis, Microsporum canis and Trichophyton mentagrophytes were
      isolated simultaneously. To the best of our knowledge this is the first case of
      mixed dermatophyte infection to be descibed in the cat. This paralell infection
      may suggests, that primary infection of one dermatophyte does not prevent the
      animal from a secondary infection.

PMID- 16886404
TI  - [Effect of fasciola hepatica larvae on the ultrastructure of digestive gland of
      Galba truncatula l].
AB  - Ultrastructure of the digestive gland has been studied in G. truncatula,
      uninfected and infected with F. hepatica larvae. The digestive gland of G.
      truncatula consist of secretory-resorption cells and calcareous cells. On the 20
      day post infection the damage to the secretory cells were small and did not
      inhibit their activity. On the 60 day post infection the gland structure was
      totally altered: reduced height of secretory cells, lack of Golgi apparatus,
      myelin-like degradation of mitochondria, reduction and desintegrating of rough
      endoplasmic reticulum. These damage of secretory and calcareous cell to bring
      about a total inhibition of their secretory activities.

PMID- 16886405
TI  - [Evaluation of functional state of blood platelets in patients infected with
      Echinococcus granulosus].
AB  - Blood platelets actively participate in defense mechanisms of the organism. eg.
      in antiparasitic immunology. The study involved 17 patients infected with
      Echinococcus granulosus. Blood for analysis was collected twice, before treatment
      (E1) and after it (E2). Control group consisted of 30 healthy people. The
      concentrations of beta-thromboglobulin and platelet factor 4 were assayed using a
      set of ASSERACHROM (Boehringer Mannheim) according to the immunoenzymatic method
      with labelled antibodies. The level of platelet factor 4 (before and after the
      antiparasitic treatment) indicates platelet activation by parasite.

PMID- 16886406
TI  - [Investigations of the development of immunity in the course of experimental
      murine toxocariasis].
AB  - Mice were infected with Toxocara canis by an oral administration of embryonated
      eggs of the parasite, then they were killed between 1st and 8th week after
      infection to obtain sera and splenic lymphocytes. The lymphocytes were kept in
      culture medium for 3 to 6 days with either concanavalin A or excretory-secretory
      antigen of T. canis and assayed for proliferative responses. The obtained sera
      were examined for the presence of specific IgG and IgM antibodies. It was found
      that cell-mediated immunity was depressed for 3 weeks after infection and the
      first signs of the developing immunity were detected only at the 4th week of
      infection. Subsequently, the blastogenic responses increased reaching a level
      significantly higher when compared with those of the control cultures at 8th week
      of infection. Specific toxocaral IgG and IgM antibodies were first detected in
      the samples collected at the 4th week.

PMID- 16886407
TI  - [The influence of intensity of Trichinella invasion on the phagocytosis of
      Candida albicans by mice macrophages].
AB  - Experiments were carried out on male Balb/c mice, weighing 20 g. The Candida
      cells (Candida albicans L 45) were killed by heat-treatment and obsonized with
      mouse serum. Macrophages were obtained from the peritoneal cavity. Phagocytosis
      was executed by incubation 0,2 ml of suspension of macrophages with 0,2 ml of
      Candida suspension. Microscopic slides with cell smear were preparated. The
      phagocytic index and the percentage of phagocytizing macrophages were calculeted.
      It was found that infection with Trichinella spiralis or Trichinella
      pseudospiralis caused a significant reduction in the phagocytic capacity and the
      percentage of phagocytizing macrophages. This reduction depended on the intensity
      of invasion.

PMID- 16886408
TI  - [Development of Pseudomonas aeruginosa infection in mice with trichinellosis].
AB  - The aim of this study was to estimate the development of P. aeruginosa infection
      in mice infected with T. spiralis or T. pseudospiralis. The investigations were
      carried out on the following strains of mice: C57Bl, C3H and B6C3F1. 20 days post
      parasitic infection P.aeruginosa were administrated by inhalation or by
      intraperitoneal injection. After 4 hrs development of infection in mice was
      evaluated (the number of bacteria in lung or in the liver tissue were counted by
      plating). It was found that the bacterial infection developed with the highest
      rate in C3H mice followed by C57B1/6, in comparison with control mice. In C3H
      mice infected with T. pseudospiralis, the number of bacteria was higher in lung
      and liver tissue, in comparison with those infected with T. spiralis. In B6C3F1
      hybrid the infection rate was significantly lower after intraperitoneal
      administration in T. spiralis infected mice. In our experiments, the development
      of P. aeruginosa infection in mice with trichinellosis was dependent on the
      strain of mice and the routes of bacteria administration.

PMID- 16886409
TI  - [The influence of intestinal nematode infection on the productivity of gilts at
      pig testing stations].
AB  - On the basis of the faecal egg counts (epg), the effect of intestinal nematode
      infection on the productive traits of gilts fattened at Pig Testing Stations
      (PTS) during 1994-1995 was evaluated. Presumably due to a full-constituent
      pelleted feed mixture given ad libitum, only in some cases the infection
      significantly lowered the daily gain, feed convertion or meat content in carcass
      of gilts, and in some--the phenomenon of resilience was observed. The highest
      influence on the productivity had station factors.

PMID- 16886411
TI  - Topographic specificity of Diplozoon paradoxum nordmann, 1832 (Monogenea:
      Diplozoidae) in the bream, Abramis brama (Linnaeus, 1758) in the Vistula Lagoon,
      Poland.
AB  - Location of the monogenean Diplozoon paradoxum on the branchial arches of the
      Vistula Lagoon bream is described. The highest number of parasites was found on
      the first gill arch, followed by the numbers recordedon the second and third
      arches; the lowest numbers of the monogenean were typical of the fourtharch.
      About 70% of the monogeneas were found to dwell on the dorsal part of the
      branchial arch. It is concluded that the distribution of parasites is controlled
      by the direction of water flow through the gills as well as the size of the gill
      arch occupied by the helminths.

PMID- 16886410
TI  - [The influence of skin parasite infection on the productivity of gilts at pig
      testing stations].
AB  - On the basis of skin scrapings collected together with cerumen from the inside of
      ears, the occurrence of a hidden mite and louse infection was assessed to
      evaluate its effect on the productive traits of gilts fattened during 1996-1997
      at Pig Testing Stations (PTS). The productivity was highly influenced by the
      station factors. The low level of infection had, however, some negative effect in
      a few cases, and in few it was not clear, probably due to the phenomenon of
      resilience.

PMID- 16886412
TI  - [Immune response of jackdaw (Corvus monedula) to antigens of Capillaria resecta
      (Nematoda)-western blotting analysis].
AB  - Biotinylated surface and somatic protein extracts of the nematode Capillaria
      resecta were analysed by SDS-PAGE followed by Western blotting in order to
      examine their antigenic character. The antigens were probing with serum of C.
      resecta naturally infected birds (jackdaws). Surface and somatic antigens were
      recognised by serum IgG, IgA and IgM antibodies. The most intense reactivity of
      sera was evident with TBS-soluble surface proteins. The present paper has shown
      that surface proteins of C. resecta are more immunogenic than somatic and they
      are able to elicit stronger immune response in the bird's body.

PMID- 16886413
TI  - Comparison of the effect of Ascaris trypsin inhibitor in various periods of mouse
      pregnancy.
AB  - Trypsin inhibitor isolated from Ascaris suum and injected into pregnant BALB/c
      mice (five times, in doses: 300 or 400 mg/kg/day) in various periods of pregnancy
      (early and late organogenesis) disturbed the development of fetuses. The nature
      and intensity of prenatal disturbances are determined by the inhibitor dose and
      time of injection. It has been found that administration of the inhibitor from 5
      th until 9-th day of gestation did not delay or prevent implantation, but caused
      a high rate of intrauterine deaths and also specific congenital malformations
      (exnencephaly and hydrocephalus). Additionally, other types of defects were noted
      in fetuses after injection of the inhibitor between 8-th and 12-th day of
      pregnancy (cleft palate, fusion of ribs). Independent of the time of injection
      during gestation the inhibitor exhibited embriotoxic effects (e.g. decreased the
      number of live fetuses per litter and mean fetal weight).

PMID- 16886414
TI  - Preliminary evaluation of maternotoxic effect of Ascaris alpha-chymotrypsin
      inhibitor in mice.
AB  - Administration intraperitoneally of the Ascaris alpha-chymotrypsin inhibitor (40
      300 mg/kg/day) at a late stage of organogenesis (8-12 days of gestation)
      disturbed course of mouse pregnancy. The low doses of alpha-chymotrypsin
      inhibitor (40-80 mg/kg/day) significantly decreased the number of live fetuses
      per litter, increased the number of fetal resorptions. The symptoms of maternal
      toxicity that occurred after administration of the highest doses of the inhibitor
      (80-300 mg/kg/day) to pregnant mice included: decreased body weight gain as
      compared to control, vaginal hemorrhage, intrauterine resorption of litters,
      abortions, altered behaviour of animals immediately after injection and death.
      There is a linear interrelationship between the logarithm of the doses of the
      inhibitor and mortality of pregnant mice. The DL50 value of the inhibitor for
      female was 116 mg/kg/day (confidence interval: 95.5-140.0 mg/kg/day).

PMID- 16886415
TI  - The effect of Ascaris trypsin inhibitor on proteolytic activity of lungs and
      kidneys of guinea pig with larval ascariosis and after ascarid homogenate
      administration.
AB  - Trypsin inhibitor, isolated from Ascaris suum tegument reduces in vitro
      proteolytic activity (pH 7) of lungs and kidneys post-nuclear fractions of guinea
      pigs with larval ascariosis, pigs after subcutaneous ascarid homogenate
      administration as well as the activity in control groups. The comparative
      analysis of effect curves of trypsin inhibitor on the organ proteases revealed
      stronger reduction of the activity of post-nuclear lung proteases in ascariosis
      and of kidneys proteases after the injection of Ascaris homogenate than the
      inhibition of the fractions activity from respective control groups.

PMID- 16886416
TI  - [An analysis of the course of experimental pneumocystosis in rats using some
      serological methods].
AB  - Since serological methods used in the diagnosis of pneumocystosis may be helpful
      to a various extent, depending on the stage of a diagnosed infection, it was
      decided to evaluate the usefulness of some the methods in the course of
      infection. Wistar rats were used in the experiments. The animals were
      administered hydrocortisone injections for 12 weeks to induce immunosuppression
      and activate naturally occurring asymptomatic infections with Pneumocystis
      carinii. Blood samples and specimes of lung tissues were collected, then they
      were examined for the presence of specific IgG and IgM antibodies, circulating
      antigen of Pneumocystsis carinii and circulating immune complexes using
      immunoenzymatic assays. The results of the above experiments indicated, that in
      an early stage of infection, the examinations of serum samples for circulating
      immune complexes were helpful, particularly for these with IgM antibodies

PMID- 16886417
TI  - Evaluation of adhesive properties of Candida albicans isolated from the oral
      cavity in HIV positive patients.
AB  - The aim of the work was to compare adhesive properties of Candida albicans
      strains isolated from the oral cavity in HIV+ vs. HIV- persons. The materials
      were Candida albicans strains and buccal epithelial cells isolated from both HIV+
      and HIV- persons. We applied the in vitro adherence test, primarily described by
      Kimura and Pearsall and modified by Macura. The strongest adherence was found
      between both fungi and epithelial cells isolated from a HIV+ person. The
      adherence of C. albicans isolated from HIV+ patients was significantly stronger
      to epithelium collected from HIV+ than HIV- persons.

PMID- 16886418
TI  - [The enzymatic activity of fungi strains isolated from the skin and skin
      appendages of humans returning from the tropics].
AB  - The aim of the work was to assess the enzymatic activity of 11 fungi strains
      isolated from the skin of 10 Lodz residents who had visited the tropics over 1998
      1999. The strains were cultured by Jeske and Lupa of The Voivodeship Outpatient
      Clinic of Infectious, Parasitic and Tropical Diseases and Fungal Infections in
      Lodz. They were as follows: Trichophyton rubrum and Acremonium kiliense from
      Zambia, Myriodontium keratinophilum, Beauveria bassiana, Cladosporium herbarum,
      Candida famata and Trichophyton yaoundei from Sudan, Trichophyton tonsurans from
      Ethiopia, Trichophyton phaseliforme from Egypt, Acremonium strictum from Zimbabwe
      and Microsporum racemosus from Tanzania. The enzymatic activity was determined
      with the use of API ZYM of bioMerieux enabling 19 hydrolases to be revealed. In
      general, all tropical strains were characterised by a weak hydrolytic activity.

PMID- 16886419
TI  - [Changes in the immune response of BALB/c mice coinfected with Heligmosomoides
      polygyrus and Trichinella spiralis].
AB  - The influence of Heligmosomoides polygyrus on infection with Trichinella spiralis
      was studied in BALB/c mice. Mice coinfected with T. spiralis and previously given
      H. polygyrus harboured both nematode species till day 34. The number of T.
      spiralis muscle larvae was greater in mice coinfected with H. polygyrus/T.
      spiralis or T. spiralis/H. polygyrus than after infection with T. spiralis alone.
      Infection with H. polygyrus did not enhance eosinophil and IL-5 levels induced by
      T. spiralis. Additionally, the production of IgG1 specific to L1 T. spiralis was
      inhibited by co-infection. Changes in the levels of IFN-gamma and IgG2a
      implicated a disturbance in Th2 cell activation during protective response and
      resulted in the greater number of T. spiralis muscle larvae in coinfected mice.

PMID- 16886420
TI  - [Co-infection of Borrelia garinii and B. afzelii in a population of wild rodents
      from woodland].
AB  - The maintenance of Borrelia burgdorferi s.l. in the environment is dependent on
      the zoonotic cycle involving tick vectors and certain reservoir hosts. It is well
      known, that the same species of wild rodents, as well as the vector Ixodes
      ricinus, are often co-infected with at least two genomospecies of B. burgdorferi
      s.l.: B. afzelii and B. garinii. The ticks collected from two rodent species:
      Clethrionomys glareolus and Apodemus flavicollis were examined for the presence
      of B. burgdorferi s.l., as well as for B. garinii and B. afzelii. In this study,
      an immunofluorescent antibody assay (IFA) and polymerase chain reaction (PCR)
      protocols were used. The high level of infestation in rodents (90% for C.
      glareolus and nearly 100% for A. flavicollis) shows that wild rodents are
      important hosts of the immature stages of I. ricinus. A high percent of Borrelia
      positive ticks collected from bank voles and yellow necked mice; above 7%
      determined by IFA and 2% determined by PCR, clearly revealed that these species
      of animals are competent zoonotic reservoirs of B. burgdorferi s.l.

PMID- 16886421
TI  - [The ecology of Cryptosporidium parvum infection in small rodent populations].
AB  - The prevalence and abundance of Cryptosporidium parvum were studied over a three
      year period (1997-1999) in three species of rodents sampled from forest and
      abandoned fields in the Mazury Lake District, Poland. The overall prevalence was
      consistently higher in voles compared with Apodemus flavicollis (70.6% in
      Clethrionomys glareolus, 73.0% in Microtus arvalis and 27.8% in A. flavicollis).
      The prevalence and abundance of infection also varied across the 3 years of the
      study with 1998 being the year of higher prevalence and abundance of the
      parasite. Fewer older animals carried the infection, and their infections were
      relatively mild. We found no consistent pattern of seasonal changes despite the
      significance of seasonal differences. Host sex did not influence either the
      prevalence or abundance of infection with C. parvum. A great proportion of
      recaptured voles developed chronic infections between consecutive trapping
      sessions and only a small number of animals recovered. However, yellow-necked
      mice seem to be much more resistant to infection that became self-limiting. Our
      results firmly establish that the common woodland and grassland wild rodents in
      the Mazury Lake District constitute a significant and hazardous reservoir of C.
      parvum for animals and humans.

PMID- 16886422
TI  - [Toxocara canis infection in dogs in Cracow's Shelter for Stray Animals].
AB  - A coprologic examination of dogs in Cracow's Shelter for Stray Animals, carried
      out between January and November 1999-2000 showed that the dogs were infected
      with Toxocara canis from 2.4% to 16.2%. The puppies were more infected that adult
      dogs: 30-72.7% and 3,3-12.2% respectively. The females are also more infected
      than males: 6.3-15.2% and 4.8-18.2% respectively.

PMID- 16886423
TI  - [Influence of free fatty acids on growth, sporulation and virulence of the
      parasitic fungus Conidiobolus coronatus].
AB  - Five free fatty acids (FFA): C16:0, C18:0, C18:1, C18:2 and C18:3 were introduced
      into culture media in order to investigate differential development of pathogenic
      fungus Conidiobolus coronatus as a function of FFA concentration. All tested FFA
      showed fungistatic action inhibiting hyphae growth and sporulation. Fungal
      colonies grown in the presence of FFA showed decreased virulence.

PMID- 16886424
TI  - [Influence of environmental factors and host on survival of first stage larvae of
      Muellerius capillaris].
AB  - The authors studied the resistance of the first stage larvae of Muellerius
      capillaris for 75 days period. The survival of larvae was estimated on larvae in
      faeces and in water. The environmental factor investigated were different
      temperatures: -18 degrees C, 3 degrees C and 20 degrees C. M.capillaris L1 showed
      the most tolerance to -18 degrees C. Survival of larvae in water differed from
      that estimated in faeces. 23,0 -100% larvae in faeces at -18 degrees C have
      survived 30 days, while about 50% larvae kept in water at 4 degrees C or 20
      degrees C survived 28 days. Age of the host was the important factor, which
      influenced survival of L1 as well. Larvae in faeces from young goats have
      survived 10 days at -18 degrees C, while larvae in faeces from old goats survived
      75 days in the same condition.

PMID- 16886425
TI  - [Extensivity of infection of Fasciola hepatica L. in cattle in Lublin's
      voivodship in the years 1993-2001].
AB  - Extensivity of infection of Fasciola hepatica L. among cattle in Lublin's
      voivodship from 1993-2001. Aim of the work was to determine extensitivity of
      appearance of hepatica among catlle put to slaughter in slaughtershouses in
      Lublin's voivodship from 1993 to 2001. Substance for the work was braught from
      the annual reports of official examination of slaughtered animals, reached from
      both main Inspectorate (department) of Veterinary in the Ministry of Agriculture
      and from Regional Institute of Veterinar's Hygiene in Lublin. Results of
      researches are as follow: extensivity of infection of Fasciola hepatica among
      cattle in Lublin and voivodship between 1993 - 1999 oscillates about 5%. In 2000
      extensivity of invasion reached 10,9%.

PMID- 16886426
TI  - [Extensivity of appearance of echinococcosis among swine in Lublin's voivodship
      in period 1993-2000].
AB  - Aim of the work was presentation of appearance of hydatid among swine in Lublin'
      s voivodship between 1993-2000. Substance for researches was brought from annual
      reports inserted into journals of official examination leaded by Veterinary's
      Inspenction of Sanitation in slaughterhouses. It was proved that average 10,1% of
      swine on territory of Lublin's voivodship in period 1993-2000 was infected.
      Frequency of infection among examined animals were the highest in last year of
      researches 200 and reached 13,4%.

PMID- 16886427
TI  - [Aspects of ecological occurrences Trichosporon cutaneum (de Beurman Gougerot et
      Vaucher, 1909 ota, 1915) in waters north-east Polands].
AB  - The aim of work was settlement of occurrence of pathogenic fungus Trichosporon
      cutaneum in diverse ecological environments. Object to investigations former
      river Wegorapa, Suprasl, lakes of complex Mamry and Sejny group, of cultivation
      ponds in Popielewo and in Poryte Jablon a few springs of city Bialystok. In
      investigations one used method of baits to isolated water fungus. Quality of
      waters determined by physico-chemistry methods. One fixed, that pathogenic fungus
      Trichosporon cutaneum stepped out in waters north-east evn Poland on all
      investigated sites. It was developed in both strong poluted water of lakes and
      ponds also in good oxygened waters and springs it was too.

PMID- 16886428
TI  - [Ecological aspects of infection of bank vole Clethrionomys glareolus (Schreber,
      1780) with Trypanosoma (Herpetosoma) evotomys Hadwen, 1912].
AB  - The studies were carried out in Kosewo Gorne in the Mazurian District (North-East
      region of Poland), in September 1995, September 1996 and between May 1997 and
      June 1998 each month. The animals were trapped in live traps, and after study
      they were marked and released. The infection of trypanosomes was detected using
      microhaematocrit centrifugation technique and in blood smears. The intensity of
      infection had the range from 50 to 150 000 individuals in 1 ml of blood. The
      maximal prevalence of infection was in August and September and there were 45%
      and 38% of infected voles respectively. The infection was detected also in May
      1998, in other months the prevalence had low level. There were no individuals of
      bank vole infected in succeeding months. The females of bank vole are more often
      infected with trypanosomes than males.

PMID- 16886429
TI  - Demodex phylloides (Acari, Demodecidae) as a specific parasite of Sus scrofa
      (Mammalia, Artiodactyla).
AB  - Within 1994-2000, sections of skin collected from eleven areas on the body of 650
      wild boars and 85 pigs living in the northern Poland and in the Great Poland were
      examined. The D. phylloides infestation in the wild boar was observed to be very
      heavy (prevalence 32%, mean intensity 74 ind.). In contrast, the domestic pig
      turned out to be free of the parasite. The wild boar D. phylloides infestations
      are symptomless. The parasite is relatively rare in the domestic pig, although
      the high animal density typical of farm stocks should aid in its spreading.
      Compared to that in the wild boar, the pigs affected show associated skin
      symptoms. Where demodicosis did occur, most often the entire population was
      suffering of the condition. Most probably, the wild boar is the original host of
      D. phylloides. The hair follicle mite in question is very frequent in the wild
      boar, but produces symptomless infestations. The parasite occurs more seldom in
      the domestic pig, but--in contrast--the infestations are much more violent.

PMID- 16886430
TI  - The occurrence of parasitic arthropods in two groups of European bison in the
      Bialowieza primeval forest.
AB  - Within 1992-2000, a total of 181 Bialowieza Forest bison were examined from two
      winter herds. Twelf parasitic arthropod species were observed, a high infestation
      being typical of Demodex bisonianius, Chorioptes bovis, Ixodes ricinus,
      Dermacentor reticulatus, and Bisonicola sedecimdecembrii. The infestation in
      section 422 herd being higher for B. sedecimdecembrii, I. ricinus, D.
      reticulatus, Ch. bovis. D. bisonianus was slightly more prevalent in the section
      391 herd, the intensity being, however, lower than that in the other herd. Among
      the remaining arthropods found in the Bialowieza Forest European bison, some
      Lipoptena cervi occurred in both herds, Demodex sp. and Sarcoptes scabiei were
      recorded only in the section 422 herd, Ixodes persulcatus was present only in the
      section 391 bison and those kept in the reservation, while D. bovis, Psoroptes
      ovis, and Melophagus ovinus were found in the reserve bison only. In the present
      study, the largest differences in the extent of infestation involved the hair
      dwelling arthropods (B. sedecimdecembrii, I. rixinus).

PMID- 16886431
TI  - The significance of the level of antibodies in the evaluation of the effects of
      treatment of toxocariasis.
AB  - The observation of a group of 168 children treated for toxocariasis shows that
      the most frequent symptoms at the time of the physical examination were abdominal
      pains--41%; headache was observed in 12% cases. Eosinophilia was found in 9.2%
      cases. The final diagnosis was based on the results of serological investigation.
      The level of IgG antibodies was established by the ELISA method using the
      excretory--secretory antigen of Toxocara canis larvae. A few years of studies
      lead to the observation that after treatment the return of the level of
      antibodies to normal is a very slow process--positive results are found in 57% of
      patients even after 4 to 7 years, and the decrease of the mean titre of
      antibodies does not exceed 45%. The observations show that examination of the
      level of antibodies in the way hitherto applied does not provide a satisfactory
      indication of the positive effect of treatment. Therefore, it is necessary to
      develop a system of additional laboratory tests that will allow a faster
      evaluation of the effects of treatment of this disease.

PMID- 16886432
TI  - [In vitro resistance of Candida species to antifungal agents].
AB  - The purpose of this study was to determine the in vitro susceptibility to 6
      antifungal agents of 143 strains of Candida species isolated from 545 patients
      with suspicion of fungal infection. Test ATB Fungus (bioMerieux) was used. Among
      all Candida isolates 91.6% were susceptible to tested polyenes and 32.9% to all
      azoles. Less susceptible to polyenes isolates were noted in low percentage (0.7
      to 4.2%) and to azoles more frequently (32.9 to 41.2%). Candida isolates
      resistant to antifungal agents tested were dependent from the kind of clinical
      samples and species of fungi. Monitoring of the susceptibility to antifungal
      agents by ATB commercial test seems to be useful tool for therapeutic purposes.

PMID- 16886433
TI  - [The treatment of extensive onychomycosis in aged patients].
AB  - The aim of the study was to present the own observations concerning treatment of
      patients above 50 years of age suffering the toe nail dermatophyte onychomycosis
      with intensified subungual keratosis and considerable nail plates destruction.
      Three different treatment methods were administered: 40 patients were treated
      only with itraconazole pulse method for 3 month, 35 patients besides itraconazole
      were given also pentoxifylline. In case of 20 individuals besides 3-month
      itraconazole pulse method treatment, the amorolfine varnish application onto
      changed nails once a week for 6 month was administered. In the group of patients
      treated only with itraconazole, in 22 cases (55,0%) the cure was obtained, while
      in the group of individuals given the combined therapy with pentoxifylline, the
      cures made 71,4% (25 individuals). From among patients treated with itraconazole
      and external amorolfine application the cures made 75,0% (15 individuals).

PMID- 16886434
TI  - [How to improve efficacy of onychomycosis treatment?].
AB  - Onychomycosis is a public health concern because of its high world wide
      prevalence, and its potential for spread of fungal elements to others. About one
      half of all patients presenting to dermatologists' offices for nail disorders
      have onychomycosis. This kind of infection may impact upon physical, functional,
      and emotional aspects of life. Onychomycosis can be treated with the new
      generation of oral antifungals. Efficacy rates for fingernail onychomycosis are
      high; however, for toenail onychomycosis, efficacy rates may range from 60% to
      80%. Relapse rates have been estimated to be 15% to 20% measured at 2 years
      following therapy initiation. Because many factors may be associated with a
      suboptimal clinical response, consideration to measures that reflect the most
      appropriate pharmacologic and supportive regimens must be made in order to meet
      the challenge of onychomycosis cure. In some situations supplemental therapy
      consisting of extra antifungal or adjunctive (topical/surgical) therapy may be
      beneficial.

PMID- 16886435
TI  - [Studies on usefullness of imidasol preparations for treatment of pulmonary and
      air sacks aspergillosis in geese].
AB  - The studies were carried out in two geese farms with a total number of 11.143 - 4
      weeks old birds. Two imidazol preparations--5 per cent Miconazole powder and 2
      Clotrimazole solution were used in these studies. Miconazole was applied as feed
      additive for 200 with aspergillosis infected geese, in a dosis of 10 mg of active
      substance on one kg of body weight. Clotrimazole was administered in a form of
      inhalation in a dose of 1,5 1 of 2 per cent solution per geese house of 3000 m3.
      Spraying was performed using gas-pipes of steam ganerator joined to the air
      compressor of the type 3 JW - 60 (6hp). In this way 5 - 10 microm partiches were
      obtained. The preparation was sprayed twice ad 2 - 4 days intervals. After
      Miconazole administration the recovery of sick birds and inhibition of the
      disease in geese were observed. The Clotrimazole preparations may be also
      administered prophylactically in geese houses, were stationary aspergillosis has
      been observed.

PMID- 16886437
TI  - [Effects of 33% grapefruit extract on the growth of the yeast--like fungi,
      dermatopytes and moulds].
AB  - Grapefruit seed extract was discovered by Jacob Harich an american immunologist
      in 1980. Assessment of the influence of grapefruit extract on the yeast-like
      fungi strains--Candida albicans growth. Material used in this investigation was
      ATCC test Candida albicans strains no 10231, 200 of Candida albicans strains, 5
      of Candida sp. strains isolated from patients with candidiasis symptoms from
      different ontocenosis and 12 of dermatophytes and moulds isolated from patients.
      The susceptibility of the Candida was determined by serial dilution method. It
      seems that 33% grapefruit extract exert a potent antifungal activity against the
      yeast like fungi strains and had low activity against dermatophytes and moulds.
      Further studies in vitro and in vivo on greater number of the yeast-like fungi
      strains and other fungi species are needed.

PMID- 16886436
TI  - [The effect of Medicago spp. on growth of Trichophyton mentagrophytes in
      microculture].
AB  - The study aimed at assessing effect of dried root and aerial parts of Medicago
      spp. on growth of Trichophryton mentagrophytes. Fungus strains were inoculated
      onto microcultures with Sabouraud agar supplemented each with 1 g of dried and
      pulverised roots or aerial parts of 3 species: Medicago arabica, M. sativa, and
      M. murex. The strongest inhibitory effect on T. mentagrophytes growth was that of
      aerial parts of M. arabica (median diameter 6 mm compared to 13 mm of control),
      followed by root of M. arabica (10 mm) and root of M. murex (10.5 mm)--in all
      cases p < 0.001. Slight inhibitory effect was also found in the case of aerial
      parts of M. murex (median diameter 12 mm, p = 0.03). In contrast, M. sativa has
      shown stimulating effect on growth of T. mentagrophytes (15 mm for root and 16.5
      mm for aerial part, p<0.001).

PMID- 16886438
TI  - Geotrichum candidum link 1809: hydrolases activity and own method of digestive
      tract strains biotyping.
AB  - Hydrolase activity of (enzymograms, biotypes) in Geotrichum candidum, one of the
      poorly described pathogenic fungi, was studied 81 strains were isolated from oral
      cavity and faeces of patients with gastrointestinal tract disorders. Axenic
      strains were differentiated with API 20C Aux and API ZYM tests. Then, enzymograms
      and biotypes were determined for all strains based on the activity of 19
      hydrolases. High variability of enzymograms (17 different types) was found. The
      highest activity was noted in case of: e2 - alkaline phosphatase, e6 - leucine
      arylamidase, e11 - acid phosphatase. E5 - lipase, e7 - valine arylamidase, e12 -
      naphtol-AS-BI-phosphohydrolase and e17 - beta-glucosidase were used for biotyping
      procedures. Our own system of biotyping of 81 strains of G. candidum was based on
      the mathematical binominal distribution formula (1 : 4 : 6 : 4 : 1) - all "+";
      one "-", three "+"; two "two "+"; three "-", one "+"; all "-". We have found: A
      (11.1 +/- 3.5%), BI (6.17 +/- 2.67%), B2 (1.23 +/- 1.22%), B4 (4.94 +/- 2.41%),
      C, (1.23 +/-1.22%), C3 (63.0 +/- 5.4%), D2 (9.88 +/-3.31%), D3 (2.47 +/- 1.72%).
      Among all strains from 8 various biotypes of G. candidum.

PMID- 16886439
TI  - Some aspects of host-fungus interactions.

PMID- 16886440
TI  - [The comparison of susceptibility of Candida albicans and Candida glabrata to
      miconazole].
AB  - Candida glabrata is very important pathogen which is resistant to some imidazoles
      (fluconazole). The aim of study was to compare a susceptibility of Candida
      albicans and Candida glabrata - strains isolated from patietnts treated in Centre
      for Treatment of Parasitic Diseases and Mycoses - to miconazole using MIC. 96.5%
      of strains were sensitive to miconazole; values of MIC for C. albicans were lower
      than for C. glabrata.

PMID- 16886441
TI  - [Activity of acid aspartic proteinase Candida strains isolated from palatine
      tonsils].
AB  - We have evalueated the activity of acidous asparagine protease in 48 strains of
      Candida isolated from homogenates of palatine tonsils from 116 patients after
      tonsilectomy. Strains most frequently isolated were C. albicans (66.7 +/- 6.8%)
      and C. tropicalis (14.6 +/- 5.09%). The range of proteolysis zone for Candida
      strains was 4.6 to 12.5 mm. Over 60% of the studied strains showed high and very
      high proteolytic activity (>6.6 mm) and the remaining strains showed moderate
      activity (4.6-6.5). There were no strains with low medium activity (to 4.5 mm
      zone). The range of the number of rosettes E formed by lymphocytes obtained from
      the studied tonsils was 0-268.3. Lymphocytes isolated from 70 % of tonsils
      infected with Candida formed only 0-130 rosettes E; in the remaining cases the
      number ranged between 131 and 220. The number of lymphocytes T forming rosettes E
      isolated from palatine tonsils from patients not infected with fungi was 2.5
      times higher. There was no correlation between the size of proteolysis zone and
      the number of rosettes E.

PMID- 16886442
TI  - [Evalution of activity of acid aspartic proteinase in Candida strains isolated
      from oral cavity of patients with increased risk of mycosis].
AB  - We have evaluated the activity of acid aspartic protease in 195 strains of
      Candida isolated from the oral cavity of three groups of patients. The first
      group comprised patients with cancer of the larynx qualified for surgery, the
      second- patients with neoplastic disease ( Hodgkin s disease, lymphoma, acute
      granulocytic leukaemia, lymphatic leukaemia, lung cancer, multiple myeloma,
      stomach cancer, breast cancer) who were not treated, the third group- patients
      with neoplastic diseases treated by chemotherapy. The strains of fungi were
      differentiated using API 20C and Api 20C AUX tests according to the protocol
      adopted at the Department of Medical Parasitology and Biology, Medical University
      of Lodz. The activity of acid protease was studied by Staib method in Rozga
      modification. Almost all strains showed high and very high proteolytic activity.
      The rang of proteolysis zone of Candida strains from the three groups of patients
      varied from 2,5 to 12,5 mm. We have found the mean proteolytic zones of strains
      isolated from groups I and III differed statistically significantly (p<0,001).
      Similarly, statisticall sihnificant difference was seen between these parameters
      for groups II and III (p<0,05), while there was no difference between strains
      from group I and II.

PMID- 16886443
TI  - The alterations in genetic apparatus of somatic and generative cells of the host
      caused by helminths metabolites.
AB  - Alterations in the genetic apparatus of mice bone marrow cells and testicles
      caused by Hymenolepis nana, Ascaris suum and Toxocara canis metabolites have been
      investigated by means of micronuclear test application. The activity of
      spermatogenesis has been investigated at experimental hymenolepidosis, migrating
      ascariasis and toxocarosis with the use of 3H-timidine. Helminths metabolites
      have been established to exert a mutagenic effect on somatic cells of bone
      marrow, spermatogonies and also on the generative cells (spermatides) of
      helminths in invaded mice. The concurrent increase in micronucleus number in
      erythrocytes, spermatogonies and in spermatides (to a lesser degree) of invaded
      mice has been revealed. The decrease in spermatogenesis activity has been
      established in experimental hymenolepidosis, migrating ascariasis and toxocarosis
      in invaded mice.

PMID- 16886444
TI  - Tissue helminthes larvae as the first xenotransplants in mammal and human
      evolution.
AB  - The review aims at explaining the role of larvae of tissue helminthes in
      suppression of protective responses of the host during xenotransplantation. We
      analyse the influence of invasion in the host by larvae of tissue helminths on
      the development of the graft against host reaction. The role of secrets and
      excrets of parasites in suppression of protective responses of the host is
      clarified at allotransplantation. The author considers the nature of
      immunodepressive components generated with larvae of helminthes in preventing
      response of the graft against host reaction. The role of corticosteroids and
      eicosanoids, secreted by parasites, in suppression of immune responses of the
      host is estimated at allotransplantation.

PMID- 16886445
TI  - [Hydrolytic activity yeast-like fungi strains isolated from Sulejow reservoir
      water].
AB  - We have investigated the hydrolytic activity of 21 species of yeast-like fungi
      from Candida genus and 1 species of yeast S. cerevisiae isolated from Sulej6w
      Reservoir water. The activity of hydrolytic enzymes of the studied fungi was
      different than that of standard strains and also of fungi isolated from patients.
      This difference demonstrates the capability of the studied fungi to adapt to
      various environmental conditions.

PMID- 16886446
TI  - [Preliminary investigations on fauna of mosquitoes (Culicinae) in Lodz and
      environs].
AB  - Species composition of mosquitoes (Diptera, Culicinae) was investigated in 2000
      year. The mosquitoes were caugh from april till october, twice a month, at 6
      stations. Seven species from genus Aedes were found: A. beclemishevi, A.
      ciprinus, A. cantans, A. flavescens, A. communis A. punctor, and A. vexans. A.
      cantans was most numerous (32,4). From genus Culex only one soecies was found
      (Culex pipiens). Furthermoce, Mansonia richardii and Culiseta annulata were
      caugh. The agresiveness toward men showed by mosquitoes was highest in august.

PMID- 16886447
TI  - [Biochemical characteristics of fungi isolated from ontocenoses of digestive
      tract in children].
AB  - Fermentation of carbohydrates and assimilation of carbon compounds were
      evaluated. The utilization of 18 specific carbon compounds was estimated in the
      investigation of each strains for differentiation of the species. From among 125
      strains of fungi the following were found: Candida albicans (112 strain), C.
      famata (2), C. glabrata (1), C. guilliermondii (1), C. kefir (4), C. tropicalis
      (2). The activity of 19 hydrolases was investigated using API ZYM. Biotyping of
      Candida strains was done according to the Williamson classification (1986),
      modified by Kurnatowska (1998). All strains were isolated from the oral cavity,
      rectum, as well as from the materials collected during endoscopy in children.

PMID- 16886448
TI  - [Fungal invasions in the digestive tract in children].
AB  - The aim of presented study were fungal invasions of the oral cavity and
      gastrointestinal (GI) tract in children suspected of the inflammation of gastric
      and duodenal mucosa and of absorption disturbance. The fungal strains (125) were
      identified using API 20C and API 20C AUX (bio Me'rieux); they were as follows:
      Candida albicans, C. famata, C. glabrata, C. guillermondii, C. kefyr and C.
      tropicalis.

PMID- 16886449
TI  - [The sensitivity to ketoconazole of Candida strains isolated from the digestive
      tract ontocenoses in children].
AB  - The study included 52 children. During endoscopy the contents of oesophagus,
      stomach and duodenum were collected with catheters, and additionally washings
      from the oral cavity and anal swabs or samples of faeces. Materials were
      inoculated on Sabouraud's media. The axenic strains of fungi were identified
      using own methods and others tests (API 20C, API 20C AUX). The activity of
      ketoconazole (K) was measured against 100 strains of Candida: C. albicans (91
      strains), C. kefyr (4), C. famata (2), C. tropicalis (1), C. guilliermondii (1),
      C. glabrata (1). The strains susceptibility to K (RO4 1400 Janssen) was estimated
      with the own system based on the dose-response curves; the minimal inhibitory
      concentration (MIC) values were canculated. The low values of MIC indicate high
      susceptibility to K of examined Candida strains.

PMID- 16886450
TI  - [Professor Roscislaw Kadlubowski: scholar and academic teacher (80th anniversary
      of his birthday].

PMID- 16886451
TI  - [Selected parasitic and infectious diseases in persons returning from the
      tropics].
AB  - Due to dramatic development of modern means of transport, exotic countries
      located on distant continents are today within a few-hour reach by a jet. Every
      year several million people travelled by air in business or as a tourists. This
      results in easy transmission of parasitic and infectious factors from continent
      to continent or from country to country. Plasmodium vivax infection: diagnosis
      concerned 6 men who had returned from Thailand, India, Senegal and Zaire. The
      parasitosis was detected as a result of thin smear of periferal blond tests -
      there were found P. vivax trophozoites an shizontes in erythrocytes. In the
      patients we found haematologic and termoregulation disturbances as well as
      hapepatosplenomegaly. Halfan was applied in therapy. Plasmodium falciparum
      infection: the infection was found in a man and a women after return from Kenya
      and Sudan. The parasitosis was detected as a result of thin smear of peripheral
      blond test - there found trophozoites of the parasite in erthorocytes. The course
      of malaria in the woman was very severe with cerebral malaria, DIC syndrome and
      blond circulation disturbances, hepatocellular and nephrocellular damage.
      Entamoeba histolytica, HAV and Candida albicans mixed infections: found in men
      who had returned from India. Severe E. histolytica infection: diagnosed in a
      women after return from Greece. There were found massive lesion of large
      intestine mucosa and high-degree disturbances. Leptospirosis icterohaemorrhagiae
      infection: found in a man after return from Belarus. Haematologic disturbance and
      hepatocellular and nephrocellular damage were observed.

PMID- 16886452
TI  - [Cryptosporidiosis in HIV-positive patients].
AB  - Cryptosporidium parvum is a coccidian parasite that affects millions of people
      worldwide. Clinical outcome of human cryptosporidiosis differs between
      immunocompetent and immnunodeficient individuals. C. parvum is responsible for
      causing protracted and life-threatening diarrhea, biliary, and pulmonary
      infections in immunocompromised persons, especially in patients with AIDS. Though
      no effective treatment has been found so far, early diagnosis may be useful in
      controlling the infection. Thirty-eight stool specimens obtained from 35 HIV
      positive patients admitted to the Clinic of Infectious Diseases in Poznan,
      Poland, were examined for the detection of oocysts, coproantigen and DNA of
      Cryptosporidium using standard microscopic, immunologic and molecular diagnostic
      methods. The presence of Cryptosporidium was detected in 10 HIV-positive
      patients. Oocysts, coproantigen and DNA of this parasite were identified solely
      in one specimen while Cryptosporidium DNA was detected in 8 specimens.
      Cryptosporidium coproantigen was found only in one sample. Although, the PCR was
      the most useful technique in the detection of Cryptosporidium in HIV-positive
      patients it should be noted that PCR has many pitfalls and needs to be carefully
      controlled to avoid both false positive and false negative results.

PMID- 16886453
TI  - [Trichomonosomycosis of the oral cavity].
AB  - Protozoa and fungi of the oral cavity, although frequently occuring and connected
      with considerable clinical adverse effects, are as yet insufficiently known. The
      aims of the study were to estimate the prevalence of common invasions of
      Trichomonas tenax and fungi, to associate the symptoms with the diagnosis of
      trichomonosis complicated by mycosis and to determine trichomonacidal properties
      of ornidazole, tinidazole and metronidazole. 936 dentist patients with different
      diagnoses were included into the study. The collected material consisted of
      rinsings, with simultaneous application of selective media, different for
      protozoa and for fungi 6ultures. Among the examined patients T. tenax was found
      in 90 cases including 85 cases where it occurred together with fungi (11
      species), on the basis of which the diagnosis of trichomonosomycosis of the oral
      cavity was established. It was the most often in patients with leukoplakia and
      Lichen Wilsoni. We received a statistically significant association (0.001
      <p<0.01) for T. tenax with fungi and xerostomia, burning sensation, periodontal
      pockets and denuded teeth. Trichomonas tenax was not found in any patiem with
      caries and with aphthe recidivans.

PMID- 16886454
TI  - [Enzootic reservoir for new Ixodes ricinus-transmitted infections].
AB  - In the last decade new tick-transmitted zoonoses have emerged as threats to the
      public health in Europe. They are mostly due to infection by Borrelia burgdorferi
      s.I., Babesia divergens, B. microti and Ehrlichia sp. All these pathogens are
      transmitted by the rodent-feeding ticks of Ixodes persulcatus "complex". Also
      there is first serological information of coexistence of antibodies to B.
      burgdorferi, B. microti and Ehrlichia sp. in human exposured to these multiple
      tick-transmitted pathogens. Actually in Poland, the identification of the host
      species that act as zoonotical reservoir for these pathogens on which the
      competent vector becomes infected, is crucial to understand the dynamics of
      enzootic cycle of these pathogens. It is also important to assess the risk factor
      of infection in different habitats, especially in environmental condition where
      changing in farming system has left great land area under grassland or pasture,
      e.g. in Mazury Lakes District. Under such circumstances, susceptible rodent
      species, at least for two of these pathogens: B. micrnti and B. burgdorfen s.l.,
      increasingly became competent reservoirs. This aspect is currently receiving
      considerable attention in Europe.

PMID- 16886456
TI  - [Physiology of ticks (Ixodida) in non-parasitic phase of life cycle].
AB  - Non-parasitic phase of ticks is the most critical period of their life cycle.
      During off host period the ticks must maintain the water homeostasis and must
      find a host for feeding. Body water homeostasis is one of the most important
      processes that influences tick survival in nature and transmission of pathogens.
      Structure of intergument, particularly the waxy lipids in the epicuticle, and
      structure of peritremes restrict the loss of water from tick body. The water
      losses may be compensated by uptake of water vapour from the atmosphere. The
      critical equilibrium humidity of tick species of Ixodidae family range from 70 to
      96% r.h. During non-feeding period, behaviour of ticks contributes to the
      maintenance of body water. The ticks aviod the microhabitats where loss of water
      may be accelerated.

PMID- 16886455
TI  - [Clinical picture of Lyme boreliosis].
AB  - Prevalence of Lyme borreliosis in Europe has been well esablished during the last
      decade. The highest morbidity in Poland, exceeding 100 cases (100.000) year, was
      demonstrated in north-estern part of the country. Additional small endemic areas
      were also described in south-western and central part of the country. Clinical
      picture of the disease do not differ significantly from observed in other parts
      of Europe. Lyme borreliosis is characterized with a wide variety of
      manifestations recognized as typical: erythema migrans, borrelial lymphocytoma,
      acrodermatitis chronica atrophicans, arthritis, facial palsy, lymphocytic
      meningitis and cardiac transduction disturbances. However there are also
      controversial syndroms, that have confirmed etiology of Borrelia burgdorferi but
      only in some cases, such as: morphea sclerodermatous lesions, cardiomyopathy and
      some neurologic disorders. Diagnosis of Lyme borreliosis is still based on
      typical signs of the disease and laboratory techniques can not solve clinical
      doubts.

PMID- 16886457
TI  - [Economic consequences of parasitic diseases in farm animals].

PMID- 16886459
TI  - [Exensivity of invasion Fasciola hepatica L. in cattle in the period 1957-1998
      and valuation of losses caused by staggers disease among cattle in Poland, 1995
      1997].
AB  - On the background of informations about frequency of appearance Fasciola hepatica
      L. among cattle in Poland in the time from 1995-1997, as well es in the former
      period, there is presented in the article an estimative apperiation of economical
      losses caused by staggers disease among cattle. The highest extensiveness of
      invasion of F. hepatica L. among cattle was noticed in the fifties and sixties
      manty in the north-eastern Poland. Losses caused by confiscation of a liver to
      amounted to 1 197 031 zl in 1995, 1 277 154 zl in 1996 and 1 312 078 zl in 1997.

PMID- 16886458
TI  - [Economical consequences of intestinal nematodes infection in pigs].
AB  - The studies wers carried out in ZZD Kolbacz on 14 sows. The experimental groups
      control and treated consisted of 7 sows each. The sows were treated with Dectomax
      - 1 ml/33 kg of body weight. The efficacy of sows treatment's was verified with
      the Wllis-Schlaaf and McMaster method. The studies indicate, that subclinical
      infection of intestinal nematodes could influence the swine production. The
      piglets from treated with Dectomax sows were infected in 8% only; when all
      piglets from non treated sows were infected with nematodes. From treated sows 0.8
      more piglet were obtained and the weight gain of litter was after 6 weeks 24.4 kg
      higher comparing with the control group.

PMID- 16886461
TI  - [The usefulnes of baycox (bayer) for coccidiosis control of lambs].
AB  - The aim the studies was to establish the usefulness of Baycox for control of
      coccidiosis and ITS influence on production results (efficiency) in lambs. The
      studies were carried out on 200 lambs, naturally infected with coccidia, divided
      in 2 groups -control and experimental, 100 animals in each, after separation from
      ewes selected in respect of sex, type, date of birth and weight. Toltrazuiril
      (Baycox) was used the first time for control of sheep coccidiosis in Poland.
      Toltrazuril was applied individual, twice at 110 and 117 day of life in a doses
      of 20 mg/kg body weight. The extensity and intensity of coccidia infection was
      ascertained by the Willis-Schlaaf and McMaster methods. The weight gain of lambs
      was stated once a month on the basis of individual weight. It was established
      that toltrazuril show a high efficiency against the protozoa of the genus Eimeria
      and drug could be used for coccidia control in lambs. This preparation is very
      active against all intracellular stages - schisogony and gamogony and it could be
      used for treatment of clinical coccidiosis. It was established profitable
      influence on the weight gain of lambs.

PMID- 16886460
TI  - [Influence of coccidiosis on productive effect in poultry husbandry].
AB  - Economical lisses due to clinical from of coccidiosis in chickens and
      prophylactic methods with special regard immunoprophy laxis were discussed.

PMID- 16886462
TI  - [The influence of coccidiostats on the course of coccidiosis and production
      results in an industrial rabbit farm].
AB  - The study was carried out on material consisting of 3375 rabbits of the White New
      Zealand breed. The total number of 9 species of coccidia were found, 8 of which
      were intestinal (E. perforans, E. media, E. magna, E. irresidua, E. coecicola, E.
      flavescens, E. piriformis oraz E. intestinalis) and E. stiedai inhabiting the
      liver. Three specirs - E . irresidua, E. coecicola and E. flavescens have been
      found in Poiand for the first time. Three of four coccidiostats examined i.e.
      Sacox, Cycostat and Baycox may be used to prevent coccidiosis in rabbit farm.
      Activity of Vetrocox is less effective and it should not be used in the
      prevention of coccidia infection. At the age of 90 days the best results were
      obtained by treatment of Sacox (257 g of increase body weight and 9 per cent
      lower mortality comparing with the control group), the second test result was
      after two doses of Baycox and after Cycostat treatment.

PMID- 16886463
TI  - [Economical consequences of coccidia infection in calves].
AB  - The studies were carried out in two farms - ZZK Kolbacz and SK Bielin, on 60
      calves, 30 animals in each farm. The calves ware divided for control and
      experimental groups -15 animals per group. Baycox was administered two times in 7
      days interval in a dosis of 20 mglkg of body weight. The weight gain and the
      course of coccidia infection in calves before and after traetment with Baycox
      ware examined. In control animals during the time of studies the coccidia
      infection was very hight. After administration of Baycox the intensity of
      coccidia infection was very low and oocysts were found in same animals, only. In
      SK Bielin before Baycox was used clinical coccidiosis and mortality of 6.9%
      calves was observed. After Baycox administration 1.9 % animals died, only. The
      results ware analyst statistically.

PMID- 16886464
TI  - [The case of acaridosis in African ostrich (Struthio camelus) breeding].
AB  - The aim of the study was to determine a reason for failing health eondition and
      deaths among the ostriches in the newly-established breeding farm situated within
      the boundaries of Torun Voivodship. Both initial observations and examinations of
      three alive and two dead birds presupposed an appearance of ectoparasitical
      disease. The autopsies were performed and the specimens for bacteriological and
      parasitological studies were subsequently obtained. The ectoparasitically
      directed studies were the only positive result; the individuals of Cnemidocoptes
      mutans and unrecognised Acarina species were found. Although the overall
      treatment (Ivomec) and breeding-rooms extermination of vermin (Neguvon 2%) were
      held, health conditions of the ostriches failed to improve and, as a result, all
      the birds died. The breeding farm was closed down wich the owner having suffered
      financially. The study allowed to draw conclusions concerning reasons for Acarina
      invasion and subsequent deaths among the birds.

PMID- 16886465
TI  - [Echinococcosis in humans in Poland and in the world. An introduction to the
      session on echinococcosis].
AB  - The activities of Associacion International de Hidatidologia, Informal WHO
      Working Groups on Research in Echinocooccosis and Japanese parasitologists group
      in Hokkaido are summarized. Progress in studying both cystic and alveolar
      echinococcoses in Poland is reviewed. In the last five years at the University of
      Medical Sciences in Poznan Poland echinococcosis was a subject of three MD thesis
      and habilitation for docent degree.

PMID- 16886466
TI  - [Up-dated progress in diagnosis and treatment of echinococcosis].
AB  - Diagnostic proces and choice of optimal management of cystic echinococcosis have
      to be related to the natural history of the parasite. The early and the late
      stages of invasion require a careful differential diagnosis with non-parasitic
      diseases. These are also the stages that many not require surgery. Chemotherapy,
      PAIR and "wait and observe approach" are alternative ways of cystic
      echinococcosis management. Em-18 WB test has a good diagnostic value in alveolar
      echinococcosis. Management of alveolar echinococcosis is based on radical
      surgery, prolonged chemotherapy and long-term observation.

PMID- 16886467
TI  - [Echinococcus granulosus and Echinococcus multilocularis invasions in north
      eastern Poland].
AB  - During the last 10 years 70 cases of echinococcosis were diagnosed in the
      Department of Infectious Diseases, Medical University School of Bialystok, of
      whom 63 were Echinococcus (E.) granulosus infections. The Urban population (70%)
      and women (60%) dominated among infected persons. Seven cases were due to E.
      multilocularis infection. A family and endemie focus of E. multilocularis human
      invasion has been identified.

PMID- 16886469
TI  - [Prevalence of the hydatidosis among swine in Poland during the period 1994
      1997].
AB  - The authors present an extensiveness of invasion of hydatidosis among swine in
      Poland. It is ascertained that a hydatidosis among swine appeared most often in
      the Eastern Poland. The analysis of these data shows that the percent infected
      animals, the highest extensiveness of invasion hydatidosis among swine occur in
      the districts Zamosc, Lomza and Chelm.

PMID- 16886470
TI  - [Application of the logistic regression procedure to the classification of
      species on an example of the genu Diplostomum Nord (Digenea)].
AB  - We introduce logistic regression procedure and explain how it can be applied for
      classification of species. This technique is more useful than traditionally used
      linear discriminant analysis since it does not require multivariate normality in
      populations being classified. Finally, the proposed approach is illustrated by an
      example of classification of four species of metacercariae of Diplosomum.

PMID- 16886468
TI  - [Suggestions concerning serological diagnosis of echinococcosis in Poland].
AB  - It has been suggested to change the present way of serological diagnosis of
      echinococcosis in Poland which utilizes immunoelectrophoresis for confirmation of
      positive results in a screening test. Diagnostic procedure should be indicated
      with a sensitive test, such as indirect haemagglutination or immunoenzymatic
      assay, and every positive result should be verifies later using a Western-blot
      method in order to detect the most specific reaction with 8 kDa fraction of
      Echinococcus antigen. Further diferentiation of the infecting species may be
      accomplished with the aid of Em2 plus ELISA test which detects antibodies
      specific for E. multilocularis.

PMID- 16886471
TI  - [Candida and amoebiasis acquired in tropical and subtropical climatic zones].
AB  - The objective of the study was the analysis of occurrence and number of Candida
      in the alimentary tract of 209 patients with intestinal amoebiasis considering
      their state after the treatment. Amoebiasis was diagnosed on the grounds of
      Entamoeba histolytica present in the faeces, what has just recently been
      recognised equal to the presence of E. histolytica complex. In all patients
      serological investigations were performed using indirect haemagglutination (IHA)
      test. The cases with relapses or with the intestinal ailments after elimination
      of the parasite from the body at the simultaneous isolation of Candida in the
      faeces were focused on. In the compass of several years a wide number of
      qualitative and quantitative mycological tests were performed comprising 39
      patients with relapses after symptomatic amoebiasis and 42 with ailments which
      had appeared after the treatment form asymptomatic amoebiasis. Observation of the
      dynamics of number of Candida cells revealed most often their increment in
      subsequent examinations. It occurred in 69% people examined after the treatment
      of asymptomatic amoebiasis and in 40,9% after the treatment of symptomatic
      amoebiasis. The differences obtained were statistically significant. The number
      of yeast remained at the same high level in 23,8% patients after asymptomatic
      amoebiasis and in 36% after symptomatic amoebiasis. Drop of Candida cells number
      was noted in 7,1% people after asymptomatic amoebiasis and in 11,4% after
      symptomatic amoebiasis. In the light of the results obtained it turns possible
      that suffering from amoebiasis could even in the long run affect Candida tendency
      to proliferate or the tendency to remain at the same high level. It may be
      presumed that the growing number of yeast was an important reason for the
      intestinal ailments after the elimination of E. histolytica. The results of
      mycoserological investigations also were taken into consideration.

PMID- 16886472
TI  - [Concentration of allergic fungi spores in the air of flats in Lodz].
AB  - The real contribution of moulds to the pathogenesis of allergic diseases remains
      unknown, although positive skin prick tests and/or specific serum IgE to moki
      allergens can be detected in 1-5% of atopic patients. A significant problem in
      assesment of exposure to mould allergens, resulting with difficulty in
      standarization of methods. The aim of this work was to assess the concentration
      of spores of 8 mould species in flats inhabited by peoples who Bont show any
      symptoms of allergy. The Open Petri Dish (OPD) method involving sedimentation of
      participles contained in the column of air over the dish was used to assess the
      number of spores in 1 m3 of indoor atmospheres. All colonies were counted, but
      only 8 mould species implicated in inhaled allergy were identified, ie.:
      Alternaria tenuis, Cladosporium herbarum, Helminthosporum halodes, Pullularia
      pullulans, Penicillium notatam, Rhizopus nigricans, Mucor mucedo, Aspergillus
      fumigatus. The tests were carried out in 10 flats located in various quarters of
      the cify of Lodz during three consecutive days of September 1995 between 5:00 pm
      and 6:04 pm. In analyzing the percentage of spores of each of the eight mould
      species tested we determined that, independent of fiat and test day, C. herbarum
      predominated. It is good agreement with the observations of other authors who
      report that among large quantities of fungi that are detected in late summer,
      usually C. herbarum spores dominate. This is the season when the incidence of the
      Cladosporium spores in the atmospheric air increases. Spores of H. halodes were
      detected least frequently. Our study demonstrated the presence of substantial
      amounts of mould spores in indoor air of houses in Lodz. The spores belong to
      species with documented allergenicity, suggesting that they may play a role in
      development of allergic sensitization in susceptible subjects.

PMID- 16886473
TI  - [Professor Bernard Bezubik, scholar and academic teacher (on his 80th birthday
      anniversary)].

PMID- 16886474
TI  - Wireless patient tracking in disaster management.

PMID- 16886475
TI  - Inventory control. Bar codes and wireless technologies help Gundersen Lutheran
      Health System manage its supply chain.

PMID- 16886476
TI  - Trends influencing the cost of care and patient safety. Decision-making in five
      key areas can improve clinical and economic performance.

PMID- 16886477
TI  - Phone-free virtual visits. Aetna covers online doctor-patient communication for
      insured members in Florida and California.

PMID- 16886478
TI  - Going Mobile. A tablet PC is the core patient care device at a new digital,
      wireless hospital in Wisconsin.

PMID- 16886479
TI  - Tablet PCs: tough enough? New Mexico's largest EMS deploys rugged, convertible
      tablet PCs to make digital chart compliance easier.

PMID- 16886480
TI  - Parental control. Iowa Health System wrangles multiple, unruly intranets and
      builds a site with flexibility and consistency for 18,400 employees.

PMID- 16886481
TI  - EHR implementation: who benefits, who pays?

PMID- 16886482
TI  - [The incongruous attitude of many physicians to the blue smoke: colleagues on the
      edge].

PMID- 16886483
TI  - [Ear infections are now in seasons--when otalgia spoils swimming fun].

PMID- 16886484
TI  - [Patient in acute danger: an opportunity to show your medical skills. Can you
      deal with an emergency?].

PMID- 16886485
TI  - [Chest pain, acute dyspnea, palpitations: internistic emergencies mandate prompt
      and appropriate action].
AB  - Patients with thoracic pain, acute dyspnea and palpitations represent an acute
      emergency for the general physician. In every case, initial information is
      provided by an ECG obtained immediately. Ifa suspected acute coronary syndrome is
      confirmed, continuous ECG rhythm monitoring must be performed. In addition,
      oxygen must be administered, the patient placed in an appropriate position, and
      analgesics and antiplatelet medication given. In the event of pulmonary edema,
      too, initial measures must include oxygen administration, appropriate
      positioning, administration of a rapid-acting loop diuretic and, where indicated,
      nitroglycerin. Should tachycardic arrhythmia occur, the width of the ventricular
      complex must be measured in the ECG before deciding on further treatment. In the
      out-of-hospital setting, no more than one antiarrhythmic should be given.

PMID- 16886487
TI  - [Prehospital care of surgical emergencies].
AB  - Surgical emergencies embrace the fields of general and visceral surgery (e.g.
      unclear/acute abdomen, blunt abdominal trauma, perianal venous thrombosis),
      vascular surgery (e.g.: venous and arterial bleeding, aortic aneurysm), accident,
      hand and plastic surgery (e.g. dislocations, fractures, amputation injuries,
      penetrating injuries, burns, hypothermia, complicated trauma, thoracic trauma).
      The prehospital treatment options discussed in the present article represent the
      current state of the art.

PMID- 16886486
TI  - [Pediatric emergencies].
AB  - Management of acute emergencies in children has a number of specific aspects,
      with which the first person providing medical care needs to be familiar. For
      example, intubation requires knowledge of the particular anatomy of infants and
      young children. In addition, a specific and flexible approach to such matters as
      oxygen requirement, blood volumes, thermoregulation and the venous system is
      essential. Administration of adrenaline should initially be via inhalation, since
      this can be done rapidly and easily. Among the causes of cardiac arrest, sudden
      infant death predominates in babies, while in young and pre-school children,
      trauma and near-drowning accidents represent the most common events requiring
      reanimation measures. Of decisive importance for clarifying the cause of death is
      an accurate documentation of the course of reanimation and the situation
      initially presenting to the care provider.

PMID- 16886488
TI  - [Squamous cell carcinoma of the nasal vestibule].
AB  - The case of a 31-year-old man (smoker) with a progressively enlarging swelling
      and reddening in the region of the nasal vestibule is discussed. Before he was
      seen by us, he had been repeatedly treated with antibiotics, but to no avail. A
      deep excisional biopsy was obtained, and the histopathological work-up revealed a
      squamous cell carcinoma. Thereupon, complete surgical ablation in healthy tissue
      was carried out. This case shows that in chronic inflammation of the nasal
      vestibule that fails to respond to antibiotic treatment differential diagnostic
      consideration must be given to the possibility of a malignancy.

PMID- 16886489
TI  - [Elevated blood pressure and anti-hypertensive therapy. Impact on sexual function
      in the male].

PMID- 16886491
TI  - [Physician must indicate unknown risks].

PMID- 16886490
TI  - [Then there will be problems with the next general practice credit].

PMID- 16886492
TI  - [Spare your ulcus cruris patients the unnecessary pain].

PMID- 16886493
TI  - [Diagnosis at a glance. "Soccer is our life..."].

PMID- 16886494
TI  - [Clinical manifestations and outcome of acute myocardial infarction in young
      adults treated with primary coronary angioplasty].
AB  - OBJECTIVES: This study investigated the differences in presentation,
      complications, and outcome of young patients with acute myocardial infarction
      compared to other patients. METHODS: Our series of 379 consecutive patients with
      acute myocardial infarction, who were admitted within 12 hr of onset and
      successfully reperfused by primary percutaneous coronary intervention, included
      28 (7.4%) young patients (< 50 years). RESULTS: There were significantly more
      male patients, current smokers, and hyperlipidemia in the young group than in the
      other patients (p < 0.01). The levels of acute phase brain natriuretic peptide
      (BNP) and atrial natriuretic peptide (ANP) were significantly lower (BNP: 128 +/-
      103 vs 379 +/- 470 pg/ml, p = 0.009, ANP: 17 +/- 11 vs 66 +/- 81 pg/ml, p =
      0.004) and peak creatine kinase value was significantly higher (3,824 +/- 3,459
      vs 2,413 +/- 2,023 IU/l, p = 0.009) in the young group than in the other
      patients. The increase (chronic phase-acute phase) of left ventricular ejection
      fraction was significantly better in the young group (8 +/- 9% vs 4 +/- 10%, p <
      0.05). There were significantly fewer patients with ventricular arrhythmia in the
      young group than in the other patients (10.7% vs 33.0%, p = 0.04). The cardiac
      mortality rate in the first 6 months was only 3.6% in the young group.
      CONCLUSIONS: Young patients with acute myocardial infarction, in spite of higher
      peak creatine kinase value, seemed to have excellent prognosis, with lower BNP
      and good recovery of left ventricular ejection fraction.

PMID- 16886495
TI  - [Clinical impact of nephropathy induced by contrast medium in patients with acute
      myocardial infarction undergoing emergent coronary angiography].
AB  - OBJECTIVES: The incidence of contrast-induced nephropathy (CIN) after coronary
      angiography and the prognostic value in patients with acute myocardial infarction
      remains to be determined. This study investigated the frequency, predictors of
      CIN, and the prognostic significance of CIN in acute myocardial infarction
      patients undergoing emergent coronary angiography. METHODS: This study included
      132 consecutive acute myocardial infarction patients undergoing emergent coronary
      angiography within 24 hr after the onset between January 1999 and June 2001. The
      serum creatinine concentration was measured on admission and at 48 hr after
      contrast medium exposure. CIN was defined as an increase in serum creatinine from
      the baseline > or = 0.5 mg/dl or > or = 25% at 48 hr after emergent coronary
      angiography. The patient characteristics, and in-hospital and long-term mortality
      were compared between the CIN and non-CIN groups. RESULTS: CIN occurred in 15
      patients (11.4%) after emergent coronary angiography. The predictor of CIN
      development was preexisting renal impairment (serum creatinine concentration > or
      = 1.2 mg/dl on presentation; 21.9% vs 8.0%, odds ratio 3.22, 95% confidence
      interval 1.07-9.74, p = 0.04). In-hospital mortality was significantly higher in
      the CIN group than in the non-CIN group (13.3% vs 1.7%; odds ratio 8.85, 95%
      confidence interval 1.15-68.2, p = 0.01). The long-term mortality (mean follow-up
      period of 40 months) was also higher in the CIN group (26.7% vs 8.6%; hazard
      ratio 3.91, 95% confidence interval 1.21-12.5, p = 0.02). CONCLUSIONS: CIN was an
      independent predictor of both in-hospital and long-term mortality in acute
      myocardial infarction patients undergoing emergent coronary angiography.
      Preexisting renal insufficiency was associated with subsequent CIN.

PMID- 16886497
TI  - Type I CD36 deficiency associated with metabolic syndrome and vasospastic angina:
      a case report.
AB  - A 54-year-old man was admitted to our hospital for evaluation of chest pain
      occurring at rest in the morning. ST segment depression was observed during a
      treadmill exercise test. Coronary angiography identified spontaneous spasm of the
      proximal right coronary artery, and right coronary obstruction was improved from
      90% to about 50% stenosis after intracoronary administration of nitroglycerin.
      Myocardial iodine-123 beta-methyl-p-iodophenyl-pentadecanoic acid uptake was
      absent, but thallium-201 uptake during single photon emission computed tomography
      was normal, and neither platelet nor monocyte expression of the CD36 molecule was
      observed, indicating type I CD36 deficiency. High blood pressure, elevated plasma
      triglyceride and fasting plasma glucose levels, and low high-density lipoprotein
      values suggested metabolic syndrome. The final diagnosis was type I CD 36
      deficiency associated with metabolic syndrome and vasospastic angina.

PMID- 16886498
TI  - [Acromegalic cardiomyopathy manifesting as asymptomatic ventricular premature
      contractions at regular medical check up: a case report].
AB  - A 32-year-old Japanese male visited our hospital on May 20, 2004 because of
      ventricular premature contractions detected at a regular medical check up. He had
      been asymptomatic with adequate exercise capacity. However, echocardiography
      findings and Holter monitoring showed impaired left ventricular systolic function
      associated with left ventricular dilation and non-sustained ventricular
      tachycardia on June 26. Coronary angiography did not show significant stenosis.
      Different types of non-sustained ventricular tachycardia could be induced by an
      electrophysiologic test, but not sustained ventricular tachycardia. The physical
      findings, such as enlargement of the nose, lips, hands and feet, suggested
      endocrinologic abnormalities, and growth hormone and somatomedin-C levels were
      elevated. Therefore, the final diagnosis was cardiomyopathy caused by acromegaly.

PMID- 16886499
TI  - [Percutaneous interventional treatment of vertebral artery stenosis with coronary
      stents: two case reports].
AB  - Two patients underwent percutaneous interventional treatment for vertebral artery
      stenosis using coronary stents. Vertebral angiography of Case 1 (78-year-old
      male) showed right ostial 100% obstruction and left ostial 99% stenosis. Balloon
      angioplasty and stent placement (Multilink 4.0 x 18 mm) were performed for the
      left vertebral artery. Vertebral angiography of Case 2 (64-year-old male) showed
      bilateral ostial severe stenoses (right 90%, left 99% + alpha). Balloon
      angioplasty and stent placement(Multilink 3.5 x 18 mm) were performed for the
      right vertebral artery. These two patients showed excellent angiographic results
      with no complication associated with stent placement. Vertebral artery
      angioplasty can be performed safely using coronary interventional equipment and
      techniques.

PMID- 16886500
TI  - [Color flow signal in the inferior septum observed after coronary angioplasty of
      the left circumflex coronary artery].

PMID- 16886501
TI  - [Ellagitannine as a topoisomerase II inhibitor].

PMID- 16886502
TI  - [Klotho: a glycosidase, slows the aging process].

PMID- 16886503
TI  - [Death of a super agonist].

PMID- 16886504
TI  - [The history of diuretics].

PMID- 16886505
TI  - [The basics of kidney physiology].

PMID- 16886506
TI  - [Pharmacology of diuretics].

PMID- 16886507
TI  - [The medicinal chemistry of diuretics].

PMID- 16886508
TI  - [Diuretics for hypertension and cardiac insufficiency].

PMID- 16886509
TI  - [Sequential nephron blockade].

PMID- 16886510
TI  - [Diuretics for the treatment of edema].

PMID- 16886511
TI  - [Economic aspects of treatment with diuretics].

PMID- 16886513
TI  - [Mugwort-- medicinal plant and drug, spice and allergen].

PMID- 16886512
TI  - [Clinical-pharmaceutical advice in diuretic therapy].

PMID- 16886514
TI  - [Geriatric and gerontologic nursing: investing in quantity or quality?].

PMID- 16886515
TI  - [Prevention of psychiatric disorders and suicide in the Belgium population older
      than 60 years. Results of the European Study on Epidemiology of Mental Disorders
      (ESEMeD)].
AB  - PURPOSE: This study aimed to examine the 12-month and lifetime prevalence rates
      of pure and comorbid mental disorders (mood, anxiety and alcohol disorders) in
      Belgian home-dwelling elderly. METHODS: A representative random sample of 665 non
      instutionalized older adults (60+) from Belgium was interviewed in 2000 and 2001.
      DSM-IV disorders were assessed by interviewers trained to use a revised version
      of the World Mental Health Composite International Diagnostic Interview (WMH
      CIDI) of the World Health Organization. RESULTS: Twenty percent of the
      respondents reported a lifetime history of at least one mental disorder; 5% met
      criteria for a a mental disorder in the past twelve months. Mood and anxiety
      disorders were the most common mental disorders. Almost 5% of the respondents
      reported suicidal ideation in their lifetime, while 0.22% had suicidal ideation
      in the past twelve months preceding the interview. CONCLUSIONS: Mental disorders
      are not uncommon in the Belgian home-dwelling elderly. The results of this study
      imply that in 2000-2001 at least five percent of the older adults living in the
      community had at least one mental disorder. Two in thousand older adults reported
      suicidal ideations in the 12 months preceding the interview.

PMID- 16886516
TI  - [Personality disorders in the elderly: diagnostic aspects].
AB  - This article describes the usefulness of the DSM personality disorders. In
      conclusion the presence of personality disorders during a lifetime is not always
      an enduring pattern of (the same) conduct disorders. Despite this, the DSM
      describes a static course of mainly interpersonal behaviour. Next to this, the
      utility of the DSM-Axis-II assessment and general personality assessment in
      relation to older adults will be discussed. In general these instruments are not
      very suitable for the assessment of the disposition and gravity of personality
      disorders in the elderly. It is proposed to develop specific profiles with regard
      to personality disorders in the elderly by applying the Delphi-technique on
      existing personality assessment. A Delphi panel of experts in the field of
      personality pathology in older adults can be asked to mention a certain
      personality disorder and describe this on a certain personality selfreport list,
      like the shortened version of the TCI.

PMID- 16886517
TI  - [Health-related fitness of sedentary elderly in the Netherlands].
AB  - The assessment of fitness is a component of a national project aimed at the
      enhancement of physical avtivity among sedentary older adults, aged 55-65 year in
      the Netherlands. Deterioration in physical functioning may be improved through an
      exercise programme. Research showed that enhancement of physical activity results
      in improved fitness, increased functional ability and health-related quality of
      life. Scientific results of the association between exercise and physical fitness
      in older adults is not sufficiently evidence-based in the Netherlands. In order
      to support health policy interventions 5.584 fitness tests of sedentary older
      adults were analyzed. The fitness was assessed by the Groninger Fitnesstest for
      Elderly (GFE). The analysis of physical fitness in sedentary older adults showed
      a lower fitness status among the age group 55-65 of age and women. Health risk
      factors such as overweight and having a chronic disease explained 88% of the
      variance between a low fitness and a high fitness profile.

PMID- 16886518
TI  - [Checklist for the detection of cognitive and emotional consequences after stroke
      (CLCE-24)].
AB  - BACKGROUND AND PURPOSE: Cognitive and emotional problems are common after stroke
      and screening is essential. In this paper a new screening instrument is presented
      and its usability is investigated. METHODS: A group of stroke patients (N = 69)
      were interviewed using the new instrument, the CLCE-24, six months post stroke.
      Moreover extensive neuropsychological testing was conducted (including
      MMSE/CAMCOG). RESULTS: Patients, relatives and assessors (a psychologist) were
      positive about its use. The interview with the CLCE-24 took 11.1 minutes on
      average (5-35 minutes). Eighty percent of the patients had complaints; 73% had
      cognitive problems, while 51% had emotional problems. Patients with at least one
      complaint on the CLCE-24 scored lower on the MMSE (t=2.5; p = 0.01) and the
      CAMCOG (t= 2.5; p= 0.02) compared to patients without complaints. CONCLUSIONS:
      The CLCE-24 can be applied by professionals in primary care for identification of
      cognitive and emotional complaints after stroke. Further research and
      implementation in clinical practice and the stroke service is recommended.

PMID- 16886520
TI  - [Centenarians and their significance for gerontology].

PMID- 16886521
TI  - [Epidemiology of late life depression].

PMID- 16886519
TI  - [Rivastigmine as adjunctive therapy in the therapeutic dilemma for the treatment
      of hallucinations due to Parkinson disease].
AB  - We report three cases of patients with Parkinson's disease without dementia,
      admitted to our hospital because of hallucinations. The anti-Parkinson medication
      was adapted and the patients started with rivastigmine. As a result,
      hallucinations no longer occurred. A 79 years old man also required short-term
      quetiapine because of agitation and anti-Parkinson doses were without side
      effects, as a result of which mobility improved. An 84 years old woman reported
      mild side effects of rivastigmine, without consequences, whereas her mobility
      appeared to be good. A 72 years old woman reported mild memory problems upon
      admission, which improved during admission, as did her mobility after increasing
      the anti-Parkinson medication doses. Treatment of rivastigmine can be useful in
      the therapeutic dilemma in the treatment of hallucinations in patients with
      Parkinson's disease (start anti-psychotic or reduce anti-Parkinson medication).
      In addition to adapting anti-Parkinson doses and sometimes short-term treating
      with an anti-psychotic, treatment with rivastigmine appears to be a quick
      improvement, without serious side effects. Also, mobility can improve, due to the
      possibility of increasing the anti-Parkinson doses, if necessary. Because of the
      many remaining questions, prospective randomised trials are needed.

PMID- 16886522
TI  - [Art and nose].
AB  - The author describes over a period of five thousands years the evolution of the
      esthetical criteria of the artists, painters and sculptors who have represented
      the nasal pyramid. Starting from prehistorical times to great civilisations:
      Roman and Greek, then to the age of the Renaissance, and to end in the modern
      times with impressionism, cubism and surrealism. As a conclusion, he draws a
      parallel between rhinoplasty and the different technical evolutions, according to
      the esthetic patterns of the rhinoplasticians and the different human qualities
      they should have to master this technique.

PMID- 16886523
TI  - [Surgical anatomy of the nose].
AB  - A good anatomical knowledge is a pre-requisite to all surgeries. In rhinoplasty,
      where many steps are performed without visual control and are only guided by
      palpation, anatomy must be mastered. Based on classical static anatomy and
      dynamic surgical modifications of the nose, this study analyses anatomical and
      surgical correlation and reports their technical implications. Correction of the
      shape of the nose is to be able to conceptualize the underlying skeleton and to
      program adapted surgical procedure for each case.

PMID- 16886524
TI  - [Rhinoplasty: morphodynamic anatomy of rhinoplasty. Interest of conservative
      rhinoplasty].
AB  - OBJECTIVES: To highlight the morphodynamic anatomical mechanisms that influence
      the results of rhinoplasty. To present the technical modalities of nasal dorsum
      preservation rhinoplasties. To determine the optimized respective surgical
      indications of the two main techniques of rhinoplasty: interruption rhinoplasty
      versus conservative rhinoplasty. MATERIALS AND METHODS: Based on anatomical
      dissections and initial morphodynamic studies carried out on 100 anatomical
      specimens, a prospective study of a continuous series of 400 patients operated of
      primary reduction rhinoplasty or septo-rhinoplasty by one of authors (YS) has
      been undertaken over a period of ten years (1995-2005) in order to optimize the
      surgical management of the nasal hump. The studied parameters were: (1) surgical
      safety, (2) quality of early and late aesthetic result, (3) quality of the
      functional result, (4) ease of the technical realization of a possible secondary
      rhinoplasty. The other selected criteria were function of the different nasal
      hump morphotypes and the expressed wishes of the patients. RESULTS: The
      anatomical and morphodynamic studies made it possible to better understand the
      role of the "M" double-arch shape of the nose and the role of the cartilaginous
      buttresses not only as a function but also the anatomy and the aesthetics of the
      nose. It is necessary to preserve or repair the arche structures of the septo
      triangular and alo-columellar sub-units. The conservative technique, whose
      results appear much more natural aesthetically, functionally satisfactory and
      durable over the long term, must be favoured in particular in man and in cases
      presenting a risk of collapse of the nasal valve. CONCLUSION: The rhinoplastician
      must be able to propose, according to the patient's wishes and in view of the
      results of the morphological analysis, the most adapted procedure according to
      his own surgical training but by supporting conservation of the osteo
      cartilaginous vault whenever possible.

PMID- 16886525
TI  - ["Mini-rhinoplasty"].
AB  - OBJECTIVES: To define the interest of the so called "mini-rhinoplasty" in
      aesthetic nose surgery and to report the surgical technique. METHOD: The
      experience of the authors, based on more than 500 mini-rhinoplasty surgical
      procedures is reported. The surgical procedure such as technical tips are
      reported. RESULTS: Mini-rhinoplasty procedure is indicated in patients with small
      deformities, particularly in patients with nasal hump or hyper-projected noses,
      with no deviation. The nasal tip should be normal or slightly drooping. The
      surgical technique is safe and reproducible. Surgical aesthetic outcomes are
      excellent. This technique is also indicated in elderly patients willing a facial
      rejuvenation. CONCLUSION: Mini-rhinoplasty surgical technique is a minimal
      invasive procedure with no complication in the postoperative period. The
      postoperative management of patients undergoing this procedure is of main
      importance.

PMID- 16886526
TI  - [Rhinoplasty: advantages and indications of the external approach].
AB  - Described for the first time in the 1930s by Rethi, the external approach would
      not have survived without its obvious advantages. It is practiced exclusively by
      certain authors giving the belief of better, more reliable or more durable
      results. This is in contrast to those who use this technique only for particular
      indications. This controversy emphases the need of evaluating the theoretical
      advantages and disadvantages of this approach relying on research. Indeed, it is
      clear to everybody that whatever the approach, the results initially depend more
      on the clinical analysis then on the qualification of the surgeon. So, if this
      controversy has no reason to be, moderate indications are probably useful to be
      set for the guidance of young rhinoplasticians.

PMID- 16886527
TI  - [Autologous cartilaginous grafts in septorhinoplasties].
AB  - The use of cartilaginous graft is very common in septorhinoplasty. OBJECTIVES:
      This article analyses the ways of harvesting and implantation of the different
      type of cartilage: septal, auricular, tragal, alar and costal. It compares their
      advantages and disadvantages. The applications of cartilaginous grafts in primary
      and secondary septorhinoplasty are studied and illustrated by some clinical
      cases. CONCLUSION: the cartilage is the most reliable means of reconstruction
      that can be used in septorhinoplasty and it is, by far, the most used by the
      majority of authors. We don't use synthetic biomaterial in nasal surgery.

PMID- 16886528
TI  - [Saddle nose surgery: long term aesthetic outcomes of support grafts].
AB  - Saddle nose surgery requires support grafts to improve the aesthestic of the nose
      such as the functional ventilation. Many kind of graft are available: Calvarial
      bone graft, iliac crest, septal cartilage, conchal cartilage, nasal hump, bony
      inferior turbinate. OBJECTIVES: To define the surgical strategy and long term
      aesthetic outcomes of rhinoplasty with support graft for saddle nose correction.
      MATERIAL AND METHOD: Retrospective study during the period 1985-2005: 160
      patients underwent rhinoplasty with support graft for saddle nose correction.
      Patients were divided into 3 groups depending on the deformation (group I: Minor
      saddle nose; group II: Intermediate saddle nose; group III: Major saddle nose).
      Long term results were analysed at least 5 years after surgery, in 70 patients.
      RESULTS: An intranasal approach was performed in 92 cases, while an open approach
      was performed in 68 cases. A bony support graft was used in 85% of patients of
      group II and 94% of patients of group III. These grafts allowed a more rigid
      correction of the saddle nose than cartilage. For groups II and III patients,
      cartilage support grafts were not used because of the lack of quantity to correct
      the saddle nose. CONCLUSION: Calvarial bone support graft has a great role in
      saddle nose surgery. The postoperative aesthetic outcomes are interesting and its
      absorption is low.

PMID- 16886529
TI  - [Surgical anatomy of the face lifting].
AB  - OBJECTIVES: Contrast between an immutable anatomy and procedures which constantly
      evolve requires a dynamic vision and knowledge of the surgical anatomy. The
      surgeon, confronted with the reality of the anatomical risk must regularly re
      examine his "basics" in anatomy and adapt them to techniques sometimes very
      invasive whose aesthetic benefit must be seriously counterbalanced by the
      operational risk. The authors endeavoured to present the surgical anatomy of the
      facelifts while insisting on the practical aspects and the concept of the
      evaluated surgical risk. METHOD: Based on more than 15 years experience related
      on the one hand to more than 400 anatomical dissections of the face and the neck
      and on the other hand on more than 600 lifts of the face and the neck, the
      authors analyze the various successive plans from the skin toward the deep
      osseous plan as they are anatomically and as the surgeon meets them. Each one of
      these plans is presented according to the various anatomical areas while
      insisting on its anatomical characteristics and its specific surgical risks.

PMID- 16886530
TI  - [Apology for the biplane cervico-facial face lift].
AB  - After a description of the physiopathology of facial ageing, the author specifies
      the interest of the biplane cervico-facial face lift to correct the tegumentary
      ptose of the lower third of the face. The various technical stages are described
      while insisting on the complementarity of the handing-over in tension of the SMAS
      (Superficial Musculo Aponevrotic System) and the redrap of the SACS (Superficial
      Adipo-Cutaneous System).

PMID- 16886531
TI  - [Facial aesthetic lipostructure].
AB  - Coleman's lipostructrure, based on the use of specific material and on a strict
      methodology has reconciled the surgeons with adipocyte transfer. The quality of
      the lipostructure results depends significantly on: The topography of the graft
      locations (the best results being obtained in the malar, chin and cheek units),
      the candidates (better results in young women, less than 60 years). The quality
      of the lipostructure results has influenced our surgical strategy: Lipostructure
      can be used alone, or frequently associated with a face lift. We adopted a
      regional operatoring strategy: A more limited zone of face lift undermining
      enabling us to target lower cheeks and neck, adjunction of lipostructure in
      adjacent anterior locations. In our experience the association face lift
      lipostructure gives good and natural results. Lipostructure is currently the best
      way to restore facial volumes.

PMID- 16886532
TI  - [Facial threads for face lift].
AB  - Facial threads have been in use for ten years as an alternative to early face
      lifting, in case of premature drooping of the face. These threads, combined with
      other techniques (lipostructure, lipoaspiration), are used for rejuvenation of
      aging face. Their mean time of action is 2 to 4 years. Main complications are
      lack of efficacy and exposure of threads through the skin or mucosa and a short
      duration of action.

PMID- 16886533
TI  - [Cervical liposuction: a reliable procedure to rejuvenate the face].
AB  - Cervical liposuction belongs to aesthetic surgical procedures. It gives a new
      oval of the face, which is a characteristic of beauty and youth. The aim is the
      reduction of sub-mental and sub-maxillary fat accumulation. This procedure is
      reliable and not invasive. This article reports on the indications of this
      procedure, insisting on the physiopathology of fat tissue, technical procedures,
      results and complications, through the experience of authors.

PMID- 16886534
TI  - [Descriptive anatomy of the eyelids: surgical interest].
AB  - The anatomy of the eyelids is complex. The author describes the limits of the
      palpebral area as well as the 5 surgical plans of the eyelids of before behind:
      Skin, the orbicular muscle, the fibro-elastic plan, deep muscles, the tarso
      conjunctival plan. The knowledge of this anatomy allows the comprehension of
      physiology, the realization of the surgery and to approach the potential risks of
      them.

PMID- 16886535
TI  - [Blepharoplasty].
AB  - INTRODUCTION: We report a study of satisfaction index of 50 patients operated of
      blepharoplasty without complications. MATERIAL AND METHODS: After a reminder of
      the anatomy of ageing palpebral and periorbital area, we describe the surgical
      techniques used to carry out the interventions according to the preoperative
      cosmetic assessment. The material used is the CO2 laser in continuous mode or the
      radio frequency in cut-coagulation mode. RESULTS: In 88% of cases, the results
      correspond to aesthetic expectations of the patients. Other criteria of
      satisfaction are detailed (treatment of the associated wrinkles, fear of changing
      of the glance). CONCLUSION: The plastic surgery of the eyelids and the glance is
      very valorizing for the surgeon. Patients' satisfaction and recognition are in
      general excellent. This is often the first step in the world of anti-age medicine
      and surgery.

PMID- 16886536
TI  - [Difficult blepharoplasties].
AB  - The effectiveness expected from aesthetic blepharoplasty is strongly related to
      the attention paid during the preoperative examination. The protocol as well as
      the proportioning of the surgical gesture are indeed likely to be influenced by
      the clinical assessment. OBJECTIVES: To emphasize the significant points of the
      local and general examination that have to be raised in order to reduce the
      incidence of complications. The delicate situations are detailed and illustrated.
      The contribution of the complementary investigations and the various surgical
      strategies are evoked. In the second part are summarized the early and late
      complications of aesthetic blepharoplasties as well as their management if they
      could not be avoided.

PMID- 16886537
TI  - [Temporal lift].
AB  - The temporal lift belongs to the traditional face lift which is in fact temporo
      cervico-facial. It also forms part of the face lift "upper part of the face"
      which is in fact temporo-frontal. It is to say that it relates to a junction zone
      between the superior and inferior part of the face. OBJECTIVES: In a first part
      the authors recall the essential anatomical data including the eyebrow, the
      Charpy's fat pad, the galea and the temporoparietal fascia, the nerves (temporo
      facial branch of the facial nerve and supra-orbital nerve) and the veins
      (sentinel vein). Then they expose the various surgical techniques (galeapexy,
      endoscopic temporal lift, brow lift, facial threads, standard fixing Endotine
      forehead, botulinic toxin. This makes it possible to define in a more precise way
      the indications and counterindications of the temporal lift. CONCLUSION: The
      indications of the temporal lift are the lateral ptosis of the tail of the brow.
      On the other hand, the total ptosis requires a frontal lift. In this case one can
      associate a concomitant blepharoplasty. The temporal lift is frequently carried
      out in a way combined with a cervico-cheek lift. The prospects for technical
      progress to improve perenniality of an isolated temporal gesture are large and
      will allow us to widen the indications.

PMID- 16886538
TI  - [Facial paralysis: functional and aesthetic rehabilitation techniques].
AB  - The diagnosis of a permanent facial paralysis can be devastating to a patient,
      because of the cosmetic, functional and psychological disorders. Our society
      places on physical appearance and leads to isolation of patients who are
      embarrassed with their paralyzed face. The objectives of the facial
      rehabilitation is to correct the functional and cosmetic losses of the patient.
      The main functional goals are to protect the eye and reestablish oral competence.
      The primary cosmetic goals are to create balance and symmetry of the face at rest
      and to reestablish the coordinated movement of the facial musculature. The
      surgeon should be familiar with the variety of options available so that an
      individual plan can be developed based on each patient's clinical picture.
      History of the facial paralysis, its etiology and the duration of the paralysis
      are of particular interest as they orientate the rehabilitation plan strategy.

PMID- 16886540
TI  - How to take a mastoid and retro auricular thin skin graft.
AB  - The mastoid and retro auricular thin skin graft has an excellent quality, and is
      easy to take. An important hydrotomu should be done in the retroauricular sulcus
      to obtain a plane surface that goes from the posterior face of the pinna to the
      skin over the mastoid surface. This plane surface is the donor site and allows
      the harvesting with the electric dermatome. The characteristics of this graft
      are: The graft have the same color of the face, the same operative field,
      yielding an unremarkable scar in the donor site. The thickness is limited to 3
      tenths of mm, and his size to 6 x 4 cm approximately.

PMID- 16886539
TI  - [Side-to-end hypoglossal-facial nerve anastomosis with intratemporal facial nerve
      translocation. Long-term results and indications in 15 cases over 10 years].
AB  - OBJECTIVES: To describe functional results concerning facial and lingual mobility
      after side-to end hypoglossal facial nerve anastomosis. MATERIAL AND METHODS: 15
      patients were operated on between 1993 and 2002 (11 cases of facial nerve injury
      during vestibular schwannoma surgery, and 4 cases of brainstem stroke). Were
      assessed at a minimum of 18 months postop tonus and facial voluntary movements
      recovery (modified House Brackmann (HB) grading), lingual mobility (amyotrophy
      and self-evaluation questionnaire), and patients' overall satisfaction
      (questionnaire). RESULTS: The mean delay to evaluation was 57.5 months. The tonus
      recovery appeared within 6 to 8 months (mean 28.5 weeks, SD 4.6 weeks). All
      patients recovered a normal tonus. The facial function was evaluated HB grade III
      in II cases (73.3%), grade IV in 3 cases (20%) and grade V in one (6.6%). Eye
      occlusion was obtained within 13.6 months on average (SD 2.6 months) in all cases
      except one. The blepharorraphy was maintained in 2 patients. No facial spasm was
      noted. The lingual motricity troubles were absent in 93.3% of cases. Patients
      were satisfied in 93.3% of cases. The less satisfactory results were observed
      when patients were managed late (>2 years after nerve section) and in case of
      brainstem stroke. CONCLUSION: This technique seems to be very efficient. It
      presents the advantage to preserve lingual motricity and to decrease
      postoperative problems of midface spasticity.

PMID- 16886541
TI  - [Botulinum toxin, description and clinical applications in the treatment of the
      face wrinkles].
AB  - The botulinum toxin is used more and more in the treatment of the wrinkles of the
      face and mainly in its 1/3 superior part. OBJECTIVES: To describe the technique
      of injection and to establish a treatment program based on the anatomical data.
      MATERIALS AND METHODS: The description of the muscles and the elements
      constituting the face makes it possible to specify the play of the muscular
      balances of the face. RESULTS: The technique of injection needs certain
      requirements: It must be of small quantity and not diffuse. The treatment program
      must be integrated in a unit based on the study of each muscular group of the
      face and the opposite skin to release a reasonable attitude in the handling in
      safety of this toxin. CONCLUSION: The technique is sure and effective by
      respecting the indications and the conditions of use.

PMID- 16886542
TI  - [How to build the legitimacy of patient and consumer participation in health
      issues?].
AB  - Initially introduced by Juppe in 1996, the legislative reforms of January 2nd and
      March 4th 2002 legally enacted new forms of consumer representation and
      participation in the development of the health system. However, it appears that
      while this new role which was created to ensure legitimate participation has been
      recognised by law in theory, it has not necessarily received the same recognition
      and incorporation in practice at the grass roots level. As a result, it is now
      essential to think about practical methods of representation in order to sustain
      local legitimacy of consumers and patients on the ground and construct it from
      the bottom-up. The goal of this work was to understand how and under what
      conditions local legitimacy for health care system consumers, as a particular
      group of actors, can be effectively built, independently and irrespective of the
      specific question of elective democratic processes. The foundation of this work
      is based on material which resides in the collection of data from various local
      participation experiments that we or other researchers have contributed to
      establishing in a select group of health care settings. The results of this
      analysis serve to update a list of principle factors through which the legitimacy
      of the health care system's users is constructed. Such factors include the
      following: the promoting agents' expectations vis-a-vis the system's users and
      the a priori status which is given to them; the identification and selection
      methods used for choosing users, and the link to the types of users in terms of
      representation; the nature of the "generalisation" process for decision-making,
      understood as the process which transforms individuals' words and perspectives
      into collective ones; and the conditions for and modes of interaction between
      laypersons and professional experts. Finally, the paper presents the potential
      conflictive relationship or tension which may exist between representation and
      legitimacy with regard to the process for building legitimacy. The authors
      discuss the links between local, direct and elective democracy. The paper
      describes how effective democratic conditions can be built on the ground (from
      self-administered legitimacy to externally acknowledged legitimacy). In
      conclusion the paper succinctly distinguishes the articulation between
      representative democracy and participatory democracy, and how local processes
      relying upon direct democracy may be properly linked to the more "classical
      representative model of democracy".

PMID- 16886543
TI  - [Investigation of the prevalence of nosocomial infection in a Tunisian regional
      hospital].
AB  - Nosocomial infections (NI) have achieved an increasingly large prevalence today,
      in Tunisia as well as abroad. Their on-going presence and occurrence are largely
      responsible for increasing morbidity and sometimes mortality. The aim of this
      work is to determine the prevalence of NI in the Kebili regional hospital and
      assess its level of impact. It consists of a cross-cutting study conducted in the
      Kebili regional hospital which holds 124 beds dispersed throughout 6 units. All
      of the patients hospitalised for more than 48 hours and who were present in the
      hospital between midnight February 17th to midnight February 18th, 2004, were
      included in the study. In the small hospital, 64 patients were present on the day
      of the study, 45 of whom had been already been hospitalised for over 48 hours.
      Among these 45, 6 patients (13%) tested positive for a NI. This prevalence is
      higher than that which is reported in the literature (2-3-9). The proportion of
      NI in this study is closer to that described in other series (2-7). In fact, we
      recorded the following : 2 cases of infection in the body zone operated upon
      (33%), 2 cases of urinary infection (33%), 1 case of pneumonia (17%), and 1 case
      of a skin infection (17%). The microbiological documentation, as it is described
      and presented in the other studies (1-7), was not found in our 6 patients here.
      The association and linkage between NI and certain other factors related to the
      provision of care has been documented as follows: surgical intervention,
      manipulations of the veins, gall bladder probing (or insertion of a catheter),
      tracheotomy, and prolonged hospitalisation (with an average stay of 16.5 days).
      The strong relationship between the occurrence of NI and the type of service or
      intervention administered during a hospital stay described in a select number of
      studies (2-5-7-11) does not present itself in our results. The overprescription
      of antibiotics among the patients in the hospital (52%) can be interpreted as a
      poor control mechanism and insufficient surveillance of the prescriptions and the
      delivery of these antibiotics, which serves as an important factor which
      contributes to NI and the development of resistance to available treatment. The
      work attempts to underline the importance of such a study on NI for the
      development and improvement of the quality of care, most importantly because the
      occurrence of NI constitutes a public health problem, and this is related to both
      the high prevalence of NI and its human and economic costs. In spite of the
      deficiencies noted in the clinical diagnoses and most notably the microbiological
      diagnoses, nosocomial infections are present in our hospital with a prevalence of
      13%.

PMID- 16886544
TI  - [Health behaviours of students at the University Institute of Technology in
      Poitiers].
AB  - Better knowledge and understanding of students' health attitudes and behaviours
      are necessary to more effectively plan targeted prevention strategies. A survey
      conducted among 617 students at the University Institute of Technology in
      Poitiers showed that although some indicators affirm good health (relationships
      with friends and family, appropriate contact with care providers in the health
      system and regular visits to prevention centres, sexual life, and sports and
      physical fitness), other indicators reveal a certain amount of suffering among
      the student population. Students reported suicidal thoughts, symptoms of poor
      well-being (fatigue, sleeping disorders, concentration problems, sadness or
      depression) and poor eating habits and/or eating disorders. Consumption of both
      legal and illegal products seems to be a means utilised to facilitate the social
      integration process for some students. Therefore, this underlines a significant
      challenge for prevention campaigns to develop an alternative role model, which
      promotes the image and profile of a healthy student, with a strong sense of self
      esteem, who is well-integrated with his peers without having to engage in
      substance abuse.

PMID- 16886545
TI  - [Modalities of drug consumption among male prostitutes].
AB  - This article deals with the modalities of licit and illicit drug consumption
      among male prostitutes and the meanings attributed to them. It is an account of a
      research carried out with a questionnaire, among 252 prostitutes (124
      transvestites and 128 hustlers), of which 30 (15 of each category) agreed to an
      in depth interview. According to the quantitative data, 79% regularly consumed
      alcohol, 75% tobacco, and 56% cannabis. During the 30 days preceding the
      research, 14 declared to have used sleeping pills, 13% poppers, 8% cocaine, and
      7% ecstasy. However, the interviews showed that not all of them shared the same
      views on the different substances and that many different consumption logics
      could be detected, pointing to different perceptions according to the context in
      which consumption occurred and their position in regard to prostitution.

PMID- 16886546
TI  - [Psychoactive substance use among newly incarcerated prison inmates].
AB  - The objective of this study was to describe the population of incoming prisoners
      in Lyon's prisons and to estimate the proportion of those who are drug users in
      order to adapt the psychological care which is made available at the time of
      entrance. During the entrance interview briefing session, a questionnaire was
      given to each new adult male inmate between January 1st and December 31st 2003.
      The mean age of new prisoners was 31 years old: 68.5% did not have regular
      employment in the last 12 months prior to their incarceration, and 52.8% had
      already been previously imprisoned. More than 64.0% of inmates declared either a
      regular use, an abusive use or dependence on tobacco, 16.5% on cannabis, 16.1% on
      alcohol, 2.5% on psychotropic medication, and 4.1% on other drugs (heroine,
      cocaine, or synthetic drugs). Moreover, 42.0% of drug users declared either a
      regular use, abusive consumption or dependence on at least two psycho active
      substances. These results confirm the need for effective screening for drug use
      upon entry into prison as a means of ensuring that appropriate psychological
      and/or psychiatric care of drug users, which is suitably adapted to the prison
      environment, can be provided.

PMID- 16886548
TI  - [Consumers and health policies: reports and perspectives].
AB  - The French public power-base imagined that the involvement and participation of
      consumers in decision-making could render the debates on health policies more
      transparent when faced with the opposing professional and techno-administrative
      logics. One could also ask oneself what is the true reality of this
      participation. The research strategy is based on the intersection and overlap of
      data resulting from the analysis of minutes reported from semi-guided interviews
      with regional and national referential persons, consumers and from documents
      concerning the construction and implementation of national, regional and local
      health policies. This study demonstrates that, from 1996 to 2002, consumers were
      associated with and implicated in the development and implementation of national,
      regional and local health policies. Exemplary success stories exist which testify
      to the possibility of anchoring a democratic consultation model in health
      institutions irrespective of the level of decision-making, application or
      operationalisation. Recommendations are proposed in order to strengthen these
      dynamic forces and relationships.

PMID- 16886547
TI  - [Evolution of functional autonomy in geriatric medium-term care units: a reliable
      performance indicator?].
AB  - The objective of this study was to compare the evolution of the level of
      functional dependence of patients between the time of their hospital admission
      and release following treatment received in the geriatric medium-term care units,
      in order to propose this variable as a clinical performance indicator for this
      type of service. The differential score of physical dependence observed was
      determined for each hospital stay, and the adjusted significant functional
      improvement rate (SFI) was calculated for every unit. This adjusted SFI rate was
      then compared to the overall rate of all of the units combined. The overall SFI
      rates were 23% in 2004. Seven of the 49 units studied present an adjusted rate
      significantly inferior to the average rate of the total number of units combined.
      This study constitutes one of the first performance analyses in the medium-term
      sector, and the adjusted SFI rate seems to be a pertinent and reliable indicator
      within this framework.

PMID- 16886549
TI  - [Evaluation and health promotion in Brittany].
AB  - A specific context combined with national devices and mechanisms, which are
      developed on a regional level, has proven to be favourable to the development of
      health promotion evaluation. The study presented here retraces the evolution of
      how this question has been approached in Brittany through a review of the
      regional literature. This work offered a means by which project funders, decision
      makers and grass-roots workers and professionals in the field could obtain a
      better perception of what issues were at stake, the challenges posed and
      perspectives to which the process adheres within the timeframe of commitment.
      Certain steps mark this process: the difficulty in creating awareness of the need
      for evaluation of health promotion following the whims upon which the development
      and formulation of projects are based; projects coming forward slowly but surely
      in support of health promotion development, of its effectiveness and which
      support the regional health policy dynamic. The expression of strong expectations
      which have been incessantly repeated emphasises the necessity and readiness for
      action today, and above all a joint willingness and responsibility of the
      professionals on the ground along with the decision-makers.

PMID- 16886550
TI  - [Risks linked to mobile phone use and how they are portrayed in the media:
      examples from three daily newspapers].
AB  - This study analyses how three French daily newspapers (Liberation, Le Monde, Le
      Figaro) convey information on the risks associated with mobile phone use in the
      period from 1995 to 2002. Quantitatively, the physical risks inherent to the low
      intensity, electro-magnetic waves are most frequently reported, followed by those
      linked to mobile phone use while driving. "Social" risks, such as those related
      to noise or uncivil behaviour, are amongst the most rarely communicated. In
      general, the media present two types of physical risks connected to mobile phone
      use: the collective ones, which cover the low-intensity electro-magnetic waves
      which are emitted from the antennas on signal base stations, and the individual
      ones, which concem the waves produced by the mobile phone itself, and the danger
      associated with its use by a driver while operating a motor vehicle. Controversy
      surrounding the current scientific studies and the uncontrollable character of
      the risks linked to the low-intensity, electro-magnetic waves instill much more
      fear and debate than around those related to the combination of driving while
      talking on the telephone. While this latter point is scientifically proven, it is
      also subjectively under control.

PMID- 16886551
TI  - [An evaluation of a patient education programme for children with asthma at a
      French teaching hospital ("l'espace du souffle", Nantes) (2002-2003)].
AB  - A program of patient education was set up at the CHU of Nantes, for groups of
      children with asthma in 1997. The aim of this study is to realize a formative
      evaluation to corelate with some effects. This study was proposed to 99 families
      with asthmatic children. A written questionnaire, was administered to the parents
      and children, exploring their satisfaction with the programme, their general
      knowledge and know-how, biomedical parameters. The observation focused on skills
      and day-to-day life with the illness. The study was completed by 21 families. The
      majority of the children, aged 7 to 11 years old, had asthma that needed
      treatment. All of the parents and children were satisfied with their visit to
      "l'espace du souffle". They all declared having increased their general knowledge
      and know-how and biomedical parameters did better. They did, however, feel that
      they did not know enough about how to recognise precursory symptoms of an attack,
      about how to practise a sport or how to use "corticoids". They also could not
      control their personal fear during an attack. During the oral questionnaire a
      general feeling of stress and worry was clearly noticeable in the parents
      feeling, that did not appear in the written questionnaire. This patient education
      program appears to be beneficial. Furthermore, this evaluation highlights some
      subjects that pass unseen during current individual consultations.

PMID- 16886552
TI  - [Knowledge and practice among health workers from the Thies region with regard to
      new malaria treatment policies].
AB  - The emergence of increasing plasmodium falciparum resistance to chloroquine in
      Africa has prompted national malaria programmes to develop new policies regarding
      appropriate and essential treatment, moving from the use of chloroquine to a new
      set of bi-therapy methods. In Senegal, the malaria treatment policy has shifted
      from chloroquine to amodiaquine/sulfadoxine-pyrimethamine. The authors studied
      the availability of these new drugs and their use by the care providers in 10
      rural health district dispensaries. Patient records were examined and nurses were
      interviewed on their knowledge about and implementation of the new policy. It was
      noted that the nurses have not yet mastered the proper use of these new
      medications, and the prescriptions given were not always in line with regulations
      and practice corresponding to the required or necessary doses. The families which
      were interviewed stated that they were not aware of the changes in treatment
      which had been recommended. The conclusion of this study was that it brought to
      the forefront the need to put specific emphasis on population information and
      awareness campaigns as well as that of ensuring that caregivers receive thorough
      training to secure the successful and sustainable implementation and maintenance
      of the new policy.

PMID- 16886553
TI  - [Identification of disturbed pupils within the educational system: comparative
      evaluation of two systems of professional practices with different approaches to
      providing guidance].
AB  - A study was carried out in the Poitou-Charentes region to assess and compare the
      professional practices in secondary schools offering two different systems of
      response and guidance. The evaluation method was based upon an analysis of the
      rates of concurrence between the evaluation of the students' answers to an
      epidemiological self-administered questionnaire filled out before a clinical
      interview, and the conclusions of the psychiatric nurses after this interview.
      Comparisons between the specific system and the standard general system of
      National Education highlighted an increased capacity of professionals in the more
      specific system to distinguish a high risk of suicidal tendencies from a low risk
      or absence of risk, while the standard system was more effective in screening and
      detecting overall levels of well-being across the entire student population.
      Moreover, the guidance support and counseling proposed in the specialised system
      seemed to better meet the pupils' needs more accurately than in the standard
      system.

PMID- 16886554
TI  - [Evaluation of the pertinence of international courses on human African
      trypanosomiasis].
AB  - The goal of this study was to evaluate the adequacy and relevance of a training
      course on Human African Trypanosomiasis, targeted to reach support and
      coordination staff in charge of activities being carried out in related
      prevention and control programmes. A questionnaire was emailed to the four course
      organisers and the 65 participants. The response rate among the participants was
      41%. The training needs expressed covered issues such as treatment, diagnostic
      and epidemiological techniques, improved knowledge of the disease, and control
      planning. The lectures given were adapted for participants' professional
      activities. At the time of the evaluation (one to three years after the course)
      67% of the participants had begun implementing the knowledge they had acquired
      and applying it to their practice, particularly in the area of programme
      planning. The analysis of the questionnaire's results pointed to the sections of
      the course that would benefit from modifications, such as the need for the
      development of lessons and modules in the areas of patient management and
      planning for future training sessions.

PMID- 16886555
TI  - [Aspects of diagnostics and prevention of toxoplasmosis].
AB  - The infection of humans with opportunistic protozoon Toxoplasma gondii is severe
      for immunocompromised individuals (AIDS patients, transplant recipients,
      fetuses). Because of the lack of protective vaccines, the rules of primary
      (avoidance) prevention have to be introduced. The principles of such prevention,
      particularly important for seronegative pregnant women, as well as new data on
      the possibility of T. gondii reinfection in seropositive humans and animals were
      presented in the article. The attention was also focused on laboratory
      diagnostics of toxoplasmosis, associated, among others, with prolonged
      persistence of specific IgM antibodies and delayed maturation of IgG antibodies.
      The psychic and physical consequences of chronic Toxoplasma gondii infections
      were mentioned (lowered IQ, schizophrenia etc.).

PMID- 16886556
TI  - [The influence of myocardial infarction on depression in patients with coronary
      artery disease].
AB  - The recent studies revealed the relation between depression and the prevalence of
      cardio-vascular diseases, as well as their complications. However the correlation
      between the risk factors of coronary artery disease and depression in patients
      suffering from cardio-vascular disorders hasn't been sufficiently examined. The
      history of myocardial infarction (MI) is a well known factor, which increases
      mortality. The aim of the study was to determine if there was any relation
      between the history of myocardial infarction and depression rate in patients with
      cardio-vascular diseases. MATERIAL AND METHODS: The study involved 163 patients,
      75 women and 88 men, aged 29 to 86 years (mean age 60.75 +/- 11.01), hospitalised
      for the purpose of undergoing coronary angiography or percutaneous transluminal
      coronary angioplasty (PTCA). Before the procedure, the symptoms of depression
      were evaluated in all the patients. Each of them filled the Beck's scale inquiry
      sheet. Two groups of patients were detached: group A consisted of patients with
      the history of MI (n = 96), group B-of patients with negative history of MI,
      diabetes who had never undergone PCI, or coronary artery bypass graft (CABG)
      before (n = 42). The control group (group C) consisted of 75 individuals, aged 20
      to 80 (mean age 45 +/- 11.14 y), who felt healthy according to WHO criteria,
      weren't on any medication, hadn't been hospitalised in previous 5 years (at any
      reason) and in whom cardio-vascular diseases and their modificable risk factors
      were excluded. RESULTS: The median of the Beck's score of depression for group A
      (9 points) was significantly higher (Wilcoxon test), than for group B (6.5
      points), p < 0.02 and for the group C (3 points), p < 0.05. (tab. 1).
      CONCLUSIONS: In patients with cardio-vascular disorders depression is more
      frequent, than in health individuals. History of MI increases the prevalence of
      depression.

PMID- 16886557
TI  - [The effect of one year of recombinant human growth hormone (rhGH) therapy on
      left ventricle structure and function in adults with severe growth hormone
      deficiency].
AB  - The aim of the study was to analyze the functional and structural changes in the
      echocardiographic parameters of the left ventricle (LV) in adult patients (pts)
      with growth hormone deficiency (GHD) without any treatment in childhood before
      and after one year long somatropin treatment. MATERIAL AND METHODS: Twelve GHD
      pts (mean age 42 +/- 10 years; M/F: 6/6) before (group GHD-1) and after one year
      rhGH therapy (group GHD-2) were compared. The s.c. rhGH treatment with somatropin
      (Genotropin, Pharmacia) at a dose 0.125 U/kg/week up to 0.25 U/kg/week has been
      continued for 1 year. Both groups were examined with echocardiography Twelve GHD
      pts (mean age 42 +/- 10 years; M/F: 6/6): with indiopatic GHD (n = 10, age from
      29 to 46 years; M/F: 6/4) and with Sheehan syndrome (n = 2, age from 46 to 61
      years; M/F: 0/2) before (group GHD-1) and after one year rhGH therapy (group GHD
      2) were compared. The s.c. rhGH treatment with somatropin (Genotropin, Pharmacia)
      at a dose 0.125 U/kg/week up to 0.25 U/kg/week (till 50 percentyl of blood IGF-1
      concentration for age and sex norm ) has been continued for 1 year. Both groups
      were examined with echocardiography. RESULTS: On echocardiography, in the group
      GHD-1 pts compared to GHD-2 pts, had lower LVM and LVMI were lower (adequately
      (138.4 +/- 39.8 vs. 153.1 +/- 49.5, p < 0.036), lower and LVMI (87.3 +/- 19.7 vs.
      96 +/- 23.7, p < 0.05). There was no Therapy had no significant therapy effect on
      systolic LV function. The diastolic function of LV did not differ between both
      GHD-1 and GHD-2 groups (E/A: 1.4 +/- 0.2 vs. 1.3 +/- 0.3 ; E: 79 +/- 17; A: 59 +/
      16 vs. 58 +/- 10, ns), but DT increased significantly from 132 +/- 21 vs. 147 +/
      30, p < 0.05). There was only significant correlation between LV systolic
      dimension after one year and IGF plasma basal concentration (r = 0.7, p < 0.01).
      CONCLUSIONS: One year medical therapy with rhGH (somatropin) is associated with a
      significant positive effect on LVM and LVMI but no significant effect on systolic
      LV function, as assessed by echocardiography in adults with GHD. Significant
      decrease of DT after therapy may suggest an influence of GH therapy on diastolic
      LV function. The level of IGF did correlate with LV systolic diameter after
      therapy.

PMID- 16886558
TI  - [ECG and 24-hour ECG findings in athletes of static and dynamic disciplines].
AB  - Endurance sports are associated with structural and functional changes in the
      myocardium. Physiologic changes representing cardiac adaptation to training are
      termed "athletic heart". THE AIM: We compared the incidence of arrhythmias and
      conduction abnormalities in athletes of static and dynamic sports using resting
      and 24 hour electrocardiography. We also studied the effect of physiologic left
      ventricular hypertrophy on the incidence of arrhythmias and conduction
      abnormalities in athletes, as well as of training duration on
      electrocardiographic parameters. MATERIAL AND METHODS: We enrolled 40 male
      athletes of static and 40 of dynamic sports, as well as 30 normally active males.
      A 12-lead resting ECG, 24 hour ECG, and echocardiography were done. RESULTS: The
      resting heart reate in athletes was significantly slower (p < 0.0001). No
      intervals longer than 3s, bundle branch or atrioventricular blocks were
      disclosed. The finding of left ventricular bypertrophy and training duration had
      no significant effect on the presence and number of supraventricular and
      ventricular arrhythmias or blocks. CONCLUSION: Resting ECG, echocardiography, and
      24 hour ECG provide valuable cardiologic information in athletes. The heart rate
      was slower in all athletes and the PQ interval was longer as compared with
      controls. No serious arrhythmias or conduction abnormalities were noted. The
      duration of training and the presence of myocardial hypertrophy had no effect on
      electrocardiographic parameters.

PMID- 16886559
TI  - [Effect of chronic therapy with low dose of angiotensin converting enzyme
      inhibitors on mortality in patients with left ventricular dysfunction after acute
      myocardial infarction].
AB  - Angiotensin converting enzyme inhibitors (ACE-I) used in patients with
      postinfarction left ventricular dysfunction reduce the risk of death. Some
      patients do not tolerate high dose of medications which benefit was well
      documented in multicentre trials. THE AIM OF THIS STUDY: was to evaluate the
      effect of low doses of ACE-I on mortality rate in patients with ejection fraction
      (EF) below < or = 35% after acute myocardial infarction (MI) in long-term
      observation. MATERIAL AND METHODS: Study population consisted of 84 patients
      (pts) (67 men and 17 women) aged 38-79 (mean age 61 +/- 11) years with post-MI
      left ventricular dysfunction (EF < or = 35%). Patients were divided into 2 groups
      according to applied treatment: the group ACE-I (+) - 50 pts who received
      captopril, enalapril, trandolapril, perindopril or quinapril at doses not
      exceeding half of target dose in chronic heart failure and the group ACE-I (-) -
      34 pts not treated with ACE-I. The end point of this observation was total
      mortality during 48 month follow-up. RESULTS: During long-term observation 33
      from 84 patients died (39%). Mortality from all causes in the group ACE-I (+) was
      non significantly reduced as compared with the group ACE-I (-) (36% vs. 44%).
      CONCLUSION: In patients with left ventricular dysfunction (EF < or = 35%) after
      acute myocardial infarction chronic treatment with low doses of ACE-I do not
      reduce total mortality rate.

PMID- 16886560
TI  - [The heart rate variability analysis in youth and children with bronchial
      asthma].
AB  - The aim of the study was analysis of the spectral parameters of heart rate
      variability (HRV) in children and youth with different intensity of bronchial
      asthma. MATERIAL AND METHODS: The study was conducted in the group of 107
      children and adolescents, aged 10-17 years, comprising 58 healthy subjects and 49
      with bronchial asthma (22 with mild and 27 with moderate asthma). Spectral HRV
      parameters at rest and under active orthostatic test conditions (5 min--supine
      position, 5 min--standing position) were analysed in two age subgroups: group A-
      children aged 10-13 years and group B--youth aged 14-17 years. RESULTS: In both
      subgroups at rest a growing tendency for high frequency components (HF) of HRV
      spectra was observed together with greater intensity of asthma. In the youth
      group with moderate asthma, the HF component (40.8 +/- 14.0 n.u.) at rest was
      significantly higher (p < 0.05) than in the age-matched control (30.8 +/- 10.7
      n.u.). In all the groups examined assuming erect position resulted in a
      significant rise in LF/HF index, which was most pronounced in the groups with
      mild (p < 0.01) and moderate asthma (p < 0.05). CONCLUSIONS: The study confirmed
      a significant association between the vagal activity in children and youth and
      frequency and intensity of bronchial asthma. A short-term HRV analysis can be
      utilised in the assessment of autonomic mechanism role in the development of
      bronchial asthma in children and youth.

PMID- 16886561
TI  - [Serological markers of arthritis in patients with chronic viral hepatitis].
AB  - Wide range of different autoantibodies (e.g. rheumatoid factor, antinuclear
      antibodies, smooth muscle antibodies, anticardiolipin antibodies) can be detected
      in low titres in more than 70% of patients with chronic hepatitis. THE AIM OF THE
      STUDY: Prevalence of serological markers typical for rheumatic diseases in
      patients with chronic viral hepatitis was examined and the correlation between
      those markers and serum activity of liver enzymes was evaluated. MATERIAL AND
      METHODS: 80 patients (30 female and 50 male aged 43.5 +/- 10 years) with chronic
      viral hepatitis hospitalized in Department of Internal Diseases and Rheumatology
      of Medical Military Institute in Warsaw were included in the study. 16 of
      patients were infected with hepatitis virus B, 60 with hepatitis virus C, 4
      suffered from both infections. Blood morphology, ESR, CRP aminotransferases
      activity, protein and bilirubin levels were measured in every patient.
      Serological examination included levels of antinuclear antibodies (ANA), smooth
      muscle antibodies (SMA), LKM-1, antineutrophil antibodies (ANCA), anticardiolipin
      antibodies (aCL), antimitochondrial antibodies (AMA), circulating immunological
      complexes (CIC), cryoglobulins and rheumatoid factor. RESULTS: At least one
      serological marker was found in 60 (75%) patients. Latex fixation reaction was
      positive in 42 (54%), rheumatoid factor was present in 25 (31%), aCL in 28 (34%),
      pANCA in 22 (27%) and CIC in 16 (20%). Antibodies ANA, AMA, LKM-1 and
      cryoglobulins were less frequently observed (6%, 5.5% and 7% respectively). The
      presence of autoantibodies was more frequent in patients with hepatitis C (77%
      vs. 62%). AMA, LKM-1 and cryoglobulins were detected only in that group of
      patients. There was no correlation between liver enzymes activity and presence of
      serological markers of rheumatic diseases. CONCLUSIONS: Serological markers
      considered to be typical for rheumatic disorders were detected in 75% patients
      (especially in patients with HCV). There is no correlation between
      aminotransferases activity and tested serological.

PMID- 16886562
TI  - [Hormonal activity of the hypophysial-gonadal axis versus the mineral bone
      density and specific markers of bone turnover in haemodialysis population].
AB  - Among the numerous complications associated with chronic renal disease both bone
      and hormonal disturbances have long been recognized. The aim of this study was to
      assess the relations between bone mineral density, gonadal status and specific
      markers of bone turnover in haemodialysis (HD) population. MATERIAL AND METHODS:
      We performed a cross-sectional study involving 40 HD patients: 27 men (mean age
      54 +/- 14, 2 years) and 13 women (mean age 58.9 +/- 9.8 years), mean HD time 68
      +/- 43 months. Serum levels of testosterone, estradiol, LH, FSH, osteocalcin
      (OC), beta-CrossLaps, iPTH and alkaline phosphatase (ALP) were measured. Bone
      mineral density (BMD) was estimated in the lumbar spine and in the femoral neck
      using dual energy absorptiometry (DXA). RESULTS: 67.5% of HD patients showed a
      low BMD. Diagnostic criteria of osteoporosis were fulfilled by 32.5% of subjects,
      they were found more frequently in women (38.5%) than in men (29.6%). Osteopenia
      was observed in 35% of patients, more frequent in women (46.2%) than in men
      (29.6%). Mean serum levels of FSH and LH were above the normal range and they
      were higher in women that in men. The serum levels of estradiol in women were
      below normal range in 11 from 13 subjects (84.6%). The mean serum testosterone
      concentrations in HD men were in normal range. We also observed a positive
      correlation between serum beta-CrossLaps concentrations and PTH (in men p <
      0.001, r = 0.66; in women p < 0.006, r = 0.71) and between serum OC levels and
      PTH (in men p < 0.02, r = 0.44; in women p < 0.01, r = 0.65), respectively.
      CONCLUSIONS; The frequency of low bone mineral density in haemodialysis patients
      is high, more common in women. Hypergonadotropic hypogonadism that occurs in
      dialysis patients may be one of the main risk factors of bone disturbances in
      these patients. The levels of bone turnover markers are mainly determined by the
      severity of hyperparathyroidism.

PMID- 16886563
TI  - [Postoperative complications in a teaching surgical ward].
AB  - Definitive cure of the disease is the essential aim of surgical proceeding.
      However in some patients who are operated on, unwanted events happen, which make
      complete recovery delayed or even impossible. These events are known as surgical
      complications. THE AIM: Presentation of quantitive and qualitative analysis of
      surgical complications registered in one year of surgical practice of Department
      of General Surgery, Orlowski Hospital, Warsaw. MATERIAL AND METHODS: In the
      period between 1.01 and 31.12.2004 we operated on 1384 patients. Complications
      were registered prospectively, during monthly analysis of patients' medical
      records. RESULTS: From the number of 1384 patients operated on, 132 patients
      developed 141 complications (10.2% complication rate in 9.5% patients).
      CONCLUSIONS: The number of surgical complications reported by other authors
      differs. This can be explained by differences in methodology of collecting data
      of complications between the studies. Registering of postoperative morbidity is
      an important issue in surgical practice. Analysis of complications can lead to
      improvement in quality of surgical care and health-care management. Introduction
      of unified system of registration of postoperative complications in all surgical
      wards would allow making an objective ranking of surgical wards on a given area.

PMID- 16886564
TI  - [Statokinesiometric assessment of equilibrium system function in military pilots
      subjected to angular accelerations].
AB  - THE AIM: Evaluation of military flight personnel is of paramount importance in
      categories both flight safety and combat effectiveness. Assessment of equilibrium
      system in military pilots is very important part of fitness to fly evaluation.
      One of the assessment methods is statokinesiometry which can be used
      complementary to standard ENT evaluation methods. MATERIAL AND METHODS: 18
      instructor pilots volunteered to take part in experiment. Age of participants was
      in range 22 to 47 years (mean 31 +/- 7.78), flight experience (240-4300 flying
      hours, mean 1408.13 +/-1054 h). All participants had current fitness to fly
      certificate. Each of participants underwent three expositions on GYRO
      Instrumental Physiological Trainer and consecutive statokinesiometric assessment
      in three conditions: "eye open" and "eye closed". RESULTS: Analysis of recorded
      parameters revealed individual variations in vestibular organ sensitivity.
      Capacity of vestibular system to cope an adapt to accelerations evoked in
      conditions similar to real flight is considered as important factor determining
      spatial disorientation susceptibility. CONCLUSIONS: Therefore it can be used as
      determinant whether certain individual is capable to perform military flight
      duties. Proposed method allows for objective and precise assessment of these
      qualities. Results obtained can be used as an objective complementation to flight
      personnel training efficiency assessment with use of aviation simulators.

PMID- 16886565
TI  - [Nonsteroidal antiinflammatory drugs and nitric oxide].
AB  - Despite of belonging to different chemical groups all nonsteroidal
      antiinflammatory drugs (NSAIDs) exert on antiinflammatory, antypyretic and
      analgetic effects inhibiting prostaglandin synthesis, preciseley inhibiting first
      enzyme in arachidonic acid- cyclooxygenase. The aim of the study was to
      investigate the influence of NSAIDs on nitric oxide synthesis and releasing to
      bloodstream Acetylsalicic acid (ASA) and diclofenac as COX-1 and COX-2 inhibitors
      and nimesulide as selective COX-2 inhibitor were used in study. MATERIAL AND
      METHODS: An experiment was carried out on male Wistar rats administered
      intragastrically with acetylsalicylic acid in doses: 2.0 and 10.0 mg/kg of body
      weigh, diclofenac in doses: 1.0 and 5.0 mg/kg body weigh and nimesulide in doses:
      2.5 and 12.5 mg/kg body weigh for three weeks. Results compared to control group
      which received water instead of achive drugs. Nitric oxide was determined by
      Nitric Oxide Non-Enzymatic Assay of Oxis International. RESULTS: ASA and
      nimesulide use did not significantly influence NO plasma concentration.
      Diclofenac administration at the 1.0 and 5.0 mg/kg of body weigh was associated
      with increased NO concentration by 48.7% and 73.5% respectively. CONCLUSION: NO
      concentration is not relevant to selective or non selective inhibition of COX by
      NSAIDs. ASA (a non selective NSAIDs) and nimesulide (sective NSAIDs) do not
      influence NO concentration, while diclofenac (non selective NSAIDs) causes an
      increase in NO blood concentration in rats.

PMID- 16886566
TI  - [The case of numerous foreign bodies in bronchial tree of both lungs and
      digestive tract].
AB  - The article shows the description of the seldom met case of simultaneous
      appearing of numerous foreign bodies situated both in air passages and in the
      alimentary canal at patient of mentally handicapped with the tendency to
      swallowing of small objects. After observing by guardians of the patients fact of
      swallowing metallic foreign bodies by him the specified research were made (X-ray
      pictures, computer tomography) and the presence in the bronchial tree of both
      lungs and in the upper and lower section of the alimentary canal were confirmed.
      Swallowed and aspirated objects did not cause no complaints at the patient.
      Revealed foreign bodies were removed from air passages by using of the
      bronchofiberoscopy method and the surgical treatment. Foreign bodies of the
      alimentary canal were voided by patient through natural tract.

PMID- 16886567
TI  - [Normoaldosterone spironolactone sensitive hypertension].
AB  - We report the case of normoaldosterone spironolactone sensitive hypertension.
      Patients suffering from this recently identified form of arterial hypertension
      exhibit clinical symptoms resembling the symptoms of primary aldosteronism. The
      described disturbances may be misdiagnosed as essential hypertension because
      plasma aldosterone levels and aldosterone/renin ratio in patients are within the
      normal ranges. In the described state of the examined female, detection of the
      disease and implementation of spironolactone treatment not only normalised
      arterial blood pressure but also allowed to avoid unnecessary administration of
      many antihypertensive agents.

PMID- 16886568
TI  - [The diagnosis of familial hypomagnesemia with hypercalciuria and
      nephrocalcinosis in a girl with acute lymphoblastic leukemia--case report].
AB  - Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is a
      rare autosomal recessive tubulopathy resulting from mutation in the gene encoding
      paracelin 1. The main symptoms of FHHNC include excessive urinary calcium and
      magnesium excretion, nephrocalcinosis, and chronic renal failure. We present 16
      year old girl in whom symptoms of FHHNC were accidentally recognized during
      therapy of acute lymphoblastic leukemia. In our patient, some symptoms of FHHNC
      were initially taken for the adverse effects of cytostatic therapy that delayed
      an adequate diagnosis. To the best of our knowledge, this is the first report of
      FHHNC associated with acute lymphoblastic leukemia. However, in our opinion this
      association is accidental.

PMID- 16886569
TI  - [Malignant lymphoma or inflammation? Diagnostic and treatment difficulties--2
      cases report].
AB  - Soft and hard tissue in the oral cavity can be the first coexisting place of
      systemic diseases manifestation. The aim of this study was to report the
      diagnostic and treatment difficulties in two patients with malignant lymphomas.
      The first case was a 66-year-old woman who had undergone surgery procedures
      connected with radiotherapy and chemotherapy because of malignant lymphoma in
      nasal cavity in 2001 year. In 2002 she was treated in our department after
      finding tumor in oral cavity, also diagnosed as malignant lymphoma. The second
      patient was a 58-year-old man who had undergone an operation (surgery) by reason
      of maxillary inflammation tumor in 2002 year. On the next year he underwent an
      operation of removal cervical lymp nodes because of malignant lymphoma. In 2004
      year he underwent surgery on account of maxillary tumor suspected by malignant
      lymphoma, which was diagnosed as inflammation. Conclusions. In differentiation
      tumors of head and neck one should take an account of lymphoma malignant. The
      similar clinic and radiological symptoms and laboratory results of malignant
      lymphomas and inflammations of head and neck can cause the late diagnosis and
      aggravate the prognosis of this severe disease.

PMID- 16886570
TI  - [Multi-reasons, severe megaloblastic anaemia--description of two cases].
AB  - We report two cases of young patients (44 and 26 years old) with severe
      macrocytic, megaloblastic anaemia in course of Addison-Biermer's disease. In
      addition we found also other reasons of vitamin B12 deficiency. The one of them
      was chronic autoimmune thyroiditis and the second was, surely, Helicobacter
      pylori infection. The presented cases confirm the importance of spreading the
      diagnosis with antithyroid antibodies detection and Helicobacter pylori test in
      all patients with Addison-Biermer's diseaese.

PMID- 16886571
TI  - [Recurrent lower gastrointestinal bleeding due to a gastrointestinal stromal
      tumor (GIST) of the small intestine].
AB  - Gastrointestinal bleeding is a common cause of hospitalisation. In most patients,
      the origin and location of bleeding can be established in routine endoscopic and
      radiological examinations. The undiagnosed cases of so-called gastrointestinal
      bleeding of unknown origin require more sophisticated diagnostic methods. We
      present a case of 35-year old man with recurrent gastrointestinal bleeding due to
      a gastrointestinal stromal tumor of the jejunum that was revealed in the visceral
      angiography.

PMID- 16886572
TI  - [Late malignant melanoma metastases within the abdominal cavity imitating
      clinically and pathologically a gastrointestinal stromal tumor].
AB  - Melanoma is a malignant skin neoplasm that often metastasizes within the
      abdominal cavity. Melanoma metastases can develop even many years after the
      primary treatment. Clinical course, microscopic histology, and
      immunohistochemical profile of melanoma may imitate a gastrointestinal stromal
      tumor (GIST). We report a case of 55-year old man with a history of melanoma
      treatment 23 years earlier who presented with recurrent duodenal bleeding from a
      neoplastic tumor that was primarily diagnosed as GIST The histology of the tumor
      was reviewed and confirmed the diagnosis of metastatic melanoma.

PMID- 16886573
TI  - [Sinonasal haemangiopericytoma of the nasal septum removed under endoscopic
      guidance].
AB  - Haemangiopericytomas originate in extravascular cells (pericytes). They are well
      differentiated tumours with low potential for local recurrence or metastasis. The
      most common presenting symptoms are nasal obstruction and recurrent epistaxis.
      Differential diagnosis requires immunohistochemical staining. Treatment consists
      in wide surgical excision. Case report a 44-years old male turned up with
      symptoms of right-sided nasal obstruction and epistaxis. A reddish, tough tumour
      10 mm in diameter was diagnosed, covered with unchanged mucous membrane with
      small ulceration 3 mm in diameter, growing in the nasal septum. The tumour was
      dissected from unchanged septal cartilage and removed under endoscopic guidance.
      Histopathological examination disclosed prolonged, multiangular cells, with no
      mitotic activity. Focal faint expression of actin was confirmed, while the tumour
      cells were negative for CD34, CD31, GFAP, EMA, CK and S-100. Endothelial cells
      were positive for CD31 and CD34. Epithelial cells were positive for EMA and CK.
      The results of differential diagnosis were consistent with the diagnosis of
      sinonasal haemongiopericytoma. The patient has been asymptomatic for 6 months.
      Conclusion. Transnasal endoscopic approach to the discussed sinonasal
      haemangiopericytoma located on the nasal septum allowed its optimal visualisation
      and removal with macroscopically sufficient margins.

PMID- 16886574
TI  - [High sensivity C-reactive protein as a complement to classical methods in the
      evaluation of coronary event's risk].
AB  - Recent years have brought many new advances concerning etiology and pathology of
      atherosclerosis and cardiovascular risk. However, there are still researches
      taking place to improve currently used Scales of Cardiovascular Risk, which
      introduce novel biomarkers of inflammatory process, hemostasis or oxidative
      stress in order to identify individuals who are the most endangered group of
      cardiovascular event. This study's aim was to review existing cardiovascular risk
      factors and risk assessment scales and to confront their clinical usefulness with
      novel biomarkers emerging in this field with special respect to high sensivity C
      reactive protein (hsCRP). Existing cardiovascular risk assessment scales seem not
      to be endangered in their prognostic role mainly due to crucial role of
      individual medical history in diagnosis ischaemic heart disease and evaluating
      the cardiovascular risk. For the time being, despite many novelties appearing in
      cardiovascular risk evaluation, only hsCRP has unarguably proven prognostic
      ability in terms of coronary events and may have addictive informative power
      towards existing cardiovascular risk scales. The level of hsCRP < 1 mg/l should
      be interpreted as low cardiovascular risk (CVR), 1-3 mg/I as moderate CVR and > 3
      mg/I as high CVR. Unfortunately, hsCRP is unpopular and not widely used in
      standard biochemical tests in Polish hospitals in patients with ischaemic heart
      disease.

PMID- 16886575
TI  - [Dialysis modality and cardiac disease in chronic kidney insufficiency].
AB  - In the paper there is presented a problem of usefulness of classical dialysis
      modalities (peritoneal dialysis--PD and intermittent hemodialysis--HD) in the
      treatment of end-stage renal disease patients, showing also cardiac disease.
      Among traditional factors accelerating development of cardiovascular disease,
      arterial hypertension is more difficult for management in patients treated with
      PD, especially after loss of residual renal function and deterioration of
      ultrafiltration capacity of the peritoneum. More atherogenic serum lipid profile
      and predisposition for thrombosis characterize in greater degree the PD than HD
      course. Among factors influencing progression of cardiovascular disease, which
      are connected with chronic kidney disease and dialysis treatment, loss of
      residual renal function and overhydration differ both modalities of dialysis
      therapy. Patients treated with PD preserve longer renal function, but
      predisposition for overhydration is greater in this group as compared to HD
      patients. An advantage of PD is no need for placement of arterio-venous fistula
      as well as more stable acid-base balance and kalemia. Relative risk of death in
      uremic patients with cardiac disease is greater in PD than in HD patients,
      especially when they suffer from diabetes mellitus. PD is preferred for severe
      cases of cardiac failure without renal insufficiency or with mild renal
      insufficiency, leading to improvement of quality of life and decreasing
      hospitalization rate.

PMID- 16886576
TI  - [Experimental methods in the treatment of Lesniowski-Crohn disease].
AB  - Lesniowski-Crohn disease (L-Ch) is a chronic inflammatory bowel disease of
      uncertain etiology that is characterized by transmural mucosal inflammation. In
      the sight of contemporary knowledge the crucial cause of L-Ch disease seems to be
      the disturbances of immunological mechanisms in the gut-associated lymphoid
      tissue (GALT). In usually conditions the intestinal mucosa persists in the state
      of controlled inflammation. Pro-inflammatory cytokines such as TNF-alpha,
      interleukins 1, 6, 8, 12 are counterbalanced by anti-inflammatory cytokines such
      as 4, 10, 11 and 13. L-Ch disease represents a state of dysregulation with
      predominance of pro-inflammatory cytokines. Standard medical therapy with agents
      like 5-aminosalicylic acid, corticosteroids, 6-mercaptopurine and azathioprine
      does not ensure the remission achievement in many patients. Therefore based on
      pro-inflammatory cytokines predominance hypothesis of L-Ch disease development,
      the new treatments with agents modulating inflammatory state are being evaluated
      in many centers. The aim of this paper is current knowledge presentation of the
      new drugs being in various phases of experimental therapies, which may be used in
      the very next future in Lesniowski-Crohn's disease treatment.

PMID- 16886577
TI  - [Expression of blood coagulation inhibitors in colon cancer].
AB  - Colon cancer morbidity in Poland is still increasing. During the course of the
      disease thromboembolic complications are often observed. It was documented that
      components of the hemostatic system influence cancer progression. The presence of
      coagulation factors was revealed in colon cancer tissue. So far the information
      on the presence of inhibitors of coagulation in this tumor type was lacking. The
      aim of the study was to evaluate the expression of coagulation inhibitors in loco
      in colon cancer. MATERIAL AND METHODS: Immunohistochemical method employing
      polyclonal antibodies directed against tissue factor pathway inhibitor (TFPI),
      antithrombin III (AT Ill), protein C (PC) and protein S (PS) was introduced.
      RESULTS: The presence of TFPI was observed in cancer cells in a part of examined
      specimens, but the intensity of the staining was different. In most cases of
      colon cancer AT III expression of low intensity was revealed in a few cancer
      foci. In approximately 15% of cases there was no AT Ill expression, while in
      other 15% of examined fragments of colon cancer AT Ill was readily detected. Weak
      expression of TM was observed in most colon cancer tissues, but only in some
      cancer foci. In 1/3 of examined cases the strong expression of TM was revealed.
      Weak and heterogeneous intensity of expression of PC was demonstrated in about
      75% of colon cancer cases, whereas in about 25% of the specimens--the expression
      of this protein was strong. Furthermore in most cases there was no or weak
      expression of PS. Only in about 25% of the cases the staining for PS was strong.
      Expression of TFPI, AT III and PC was revealed in macrophages, whereas TFPI and
      AT Ill were detected in mucus in the lumen of neoplastic glands, and TM--in
      endothelial cells. CONCLUSIONS: Weak representation or the lack of coagulation
      inhibitors in colon cancer in most cases may facilitate coagulation activation in
      the tumor burden, and consequently promote colon cancer progression.
      Heterogeneous and inconstant presence of blood coagulation inhibitors in colon
      cancer in loco may suggest, that nonocoagulant biological activities of these
      inhibitors may influence the cancer growth or its inhibition in an individual
      patient. Obtained results suggest that introducing various forms of blood
      coagulation inhibitors in the treatment of colon cancer patients may be
      beneficial in selected group of patients.

PMID- 16886578
TI  - [Genetics in rheumatoid arthritis (RA)].
AB  - Rheumatoid arthritis (RA) is a chronic autoimmune disease. Genetic and
      environmental factors are implicated in the pathogenesis of RA. In this study we
      describe numerous genetic phenomena that may be implicated in the
      etiopathogenesis of RA i.e. antigens of major histocompatibility complex, genetic
      linkage analysis results of whole genome scan and polymorphism of several genes
      coding receptors, adhesion molecules and cytokines. Genetic background plays an
      important role in this disorder and is connected with multiple genes.

PMID- 16886579
TI  - [Cerebrospinal rhinorrhea--etiology, clinical signs and laboratory diagnosis].
AB  - Last studies have shown unsatisfactory diagnosis of cerebrospinal rhinorrhea.
      Although the majority of cerebrospinal (CSF) fistulas in the anterior skuli base
      are traumatic in nature, the minority is non-traumatic or primary. The authors
      have made an attempt of presenting on the basis of scientific reports of the
      physiopathology, imagin and diagnosis of cerebrospinal fluid leaks. This article
      introduces rapid, accurate and non-invasive biochemical methods for detection of
      cerebrospinal fluid leakage using combined determination of glucose, beta-trace
      protein and beta-2-transferrin in secretion and serum. There are presented new
      invasive techniques for detection and localization of the cerebrospinal fluid
      leaks: CT and CT with contrast, MR cisternography and MRI cisternography in
      combination with single photon emission tomography. Finally, discusses different
      opinion in the management of the problem once it occurs.

PMID- 16886580
TI  - [Precocious puberty].
AB  - Precocious puberty is usually defined as the appearance of secondary sexual
      development before the age of 8 years in girls and 9 years in boys. Precocious
      puberty is a heterogenous condition generally divided into central and peripheral
      forms driven respectively by hypothalamic-pituitary axis or by excessive
      production of sex steroids. Taking into account the risk associated with the
      underlying disorder as well as the impact of precocious puberty on stature growth
      and development of reproductive and mental functions, this condition has
      important consequences for affected children and their families. In this paper,
      the pathophysiology, clinical presentation, laboratory and radiological features,
      and treatment of the disorders leading to precocious puberty are reviewed.
      Particular attention is devoted to the results of the recently published studies.

PMID- 16886581
TI  - [Botulinum toxin--phenomenon of poison].
AB  - In the article, authors described possibilities of application botulinum toxin in
      medicine. Botulinum toxin is widely used in aesthetical medicine, especially in
      anti-aging therapy, but also in neurology and ophthalmology, as an effective
      method of treating clinical situations caused by excessive muscle spasms. The
      toxin is also used in the treatment of other medical disorders as well as in
      cosmetology, especially in correction of mimic wrinkles in 1-3 upper part of the
      face, with a great efficacy and very low side effects risk factor. Therapeutic
      and cosmetic effects in these procedures are very promising and a level of
      discomfort for patients definitely minimalized.

PMID- 16886582
TI  - [Intra-abdominal hypertension and abdominal compartment syndrome--therapeutic
      implications].
AB  - Abdominal compartment syndrome (ACS) involves progressive uncontrolled increase
      in intra-abdominal pressure which eventually leads to multi organ failure.
      Therefore the ability to diagnose and adequately treat ACS is so important in
      hospital practice. The aim of this paper was to review current data on intra
      abdominal hypertension and ACS, with emphasis on practical aspects. The article
      presents main concepts, symptoms, causes, pathophysiology and diagnosis of
      abdominal hypertension and abdominal compartment syndrome (ACS). The article also
      describes the key elements of contemporary strategy of treatment and prevention
      of the condition.

PMID- 16886584
TI  - [The role of adiponectin in atherosclerosis].
AB  - Adiponectin is a adipose tissue-derived protein. In the light of current
      investigations, the role of adiponectin goes far beyond only adipose tissue
      regulatory factor, being involved in some pathological processes as endothelium
      damage or atherosclerosis. Unique properties of adiponectin make it a very
      promising agent that posses ability to slow down the progression of
      atherosclerosis. In this article, a structure and a function of adiponectin have
      been reviewed. The special emphasis was put upon the role of adiponectin in
      atherosclerosis.

PMID- 16886583
TI  - [Obesity influence on renal function].
AB  - Obesity is an increasing problem in all over the developed world. The paper
      describes the substances secreted by adipose tissue and the altered renal
      hemodynamics in obese subjects. The review pays attention to diagnostic
      difficulties and discusses the medical trials of this pathology.

PMID- 16886585
TI  - Effect of a high-fat meal on the growth hormone response to exercise in children.
AB  - Exercise-induced growth hormone (GH) secretion may significantly modulate growth
      and development in children. Altered physiological GH responses, therefore, may
      reduce the beneficial effects of exercise. High-fat food ingestion before
      exercise blunts the GH response in adults, but it is unknown whether this occurs
      in children. We therefore performed standard exercise tests, following a high-fat
      meal or placebo, in 12 children, age 11-15 (6 M, 6 F). GH, insulin-like growth
      factor-I, glucose, insulin, glucagon, cortisol, epinephrine and interleukin-6
      samples were drawn at baseline, end-exercise, and 30 and 60 min post-exercise.
      While GH was similar at baseline in all experiments, the exercise-induced GH peak
      was lower after the high-fat meal (6.7 +/- 1.6 ng/l vs 11.8 +/- 2.4 ng/l, p
      <0.02). Other exercise responses were not affected by prior fat ingestion. A high
      fat meal before exercise, therefore (a common event in Western societies), may
      reduce the growth factor response to exercise in children, with potential
      implications for growth and development.

PMID- 16886586
TI  - Acquired neonatal thyroid disease due to TSH receptor antibodies in breast milk.
AB  - INTRODUCTION: We investigated whether thyroid receptor antibodies (TRAb) could
      result in transient neonatal thyroid disease by transfer through milk from
      mothers treated for thyrotoxicosis. AIM: To analyse whether breast milk content
      of TRAb in euthyroid mothers with treated thyrotoxicosis resulted in neonatal
      thyroid disease and whether extended breastfeeding prolonged the neonatal
      disease. PATIENTS: We tested three TRAb-positive mothers and the course,
      treatment and outcome for their offspring with neonatal thyrotoxicosis, and six
      healthy and two TRAb-negative euthyroid mothers with treated thyrotoxicosis
      during breastfeeding. METHOD: TRAb was analysed in serum and breast milk by a
      radioreceptor assay. RESULTS: TRAb in serum was detectable in all treated
      mothers, in one mother during her four pregnancies, resulting in all neonates
      requiring treatment for thyrotoxicosis. Serum TRAb concentration in neonates
      decreased continuously with time after birth. Breast milk TRAb was detectable in
      all cases but not in the controls or in TRAb-negative mothers treated for
      thyrotoxicosis. The calculated half-life for offspring serum and breast milk TRAb
      was calculated as approx. 3 weeks and 2 months, respectively. CONCLUSION:
      Euthyroid TRAb-positive mothers may cause transient neonatal thyroid disease
      which seems to be worse and more prolonged during breastfeeding as a consequence
      of TRAb in breast milk.

PMID- 16886587
TI  - Effects of diacylglycerol oil on adiposity in obese children: initial
      communication.
AB  - Several studies have shown that diacylglycerol (DAG) oil may suppress
      accumulation of body fat in adults compared to triacylglycerol (TAG) oil. In this
      study, we investigated the effect of DAG oil as part of dietetic therapy in obese
      children. The participants were 11 male and female obese children who were under
      treatment at the outpatient clinic (four boys, seven girls, age: 7-17 years old).
      Daily-use cooking oil was changed to DAG oil, and the effects on abdominal fat
      areas, adipocytokines, and serum lipids were investigated. The total and
      subcutaneous fat areas significantly decreased in the 5th month after ingestion
      of DAG oil. Leptin was significantly lower than the initial level after ingestion
      of DAG oil. The ingestion of DAG oil decreased both the abdominal fat area and
      leptin in obese children, suggesting that DAG oil prevents obesity in children as
      well as in adults.

PMID- 16886588
TI  - Bone mineral density and alterations of bone metabolism in children and
      adolescents with type 1 diabetes mellitus.
AB  - OBJECTIVES: To analysis bone mineral density (BMD) and bone turnover markers in
      children and adolescents with type 1 diabetes mellitus (DM1) and to establish
      possible correlations with duration of the disease and degree of metabolic
      control. PATIENTS AND METHODS: Fifty-eight (26 prepubertal, 32 pubertal) children
      (29 boys) with DM1 (age: 11.7 +/- 3.1 years) and 44 (20 prepubertal, 24 pubertal)
      healthy children (21 boys) as controls (age: 10.8 +/- 3.2 years) were included in
      the study. BMD was measured by dual energy X-ray absorptiometry (DEXA). Scans of
      the lumbar spine (LS2-4) and femoral neck (FN) were carried out. Serum levels of
      osteocalcin, amino-terminal propeptide of type I procollagen (PINP), and alkaline
      phosphatase, as markers of bone formation, and urinary calcium/creatinine (Ca/Cr)
      ratio and levels of N-telopeptide (Ntx), as markers of bone resorption, were
      assessed. Anthropometrics, duration of DM1, presence of complications, insulin
      dose, and degree of metabolic control were obtained from the patients' records.
      RESULTS: In children with DM1 and controls, the mean measurements of LS2-4 BMD
      were 0.698 +/- 0.178 g/cm2 and 0.669 +/- 0.192 g/cm2, respectively (p >0.05), and
      FN-BMD measurements were 0.743 +/- 0.147 g/cm2 and 0.744 +/- 0.170 g/cm2,
      respectively (p >0.05). Children with DM1 had lower serum levels of calcium,
      intact parathyroid hormone, osteocalcin and PINP, and higher serum levels of 25
      hydroxyvitamin D and urinary Ca/Cr (p <0.05). BMD was not related to any of the
      markers of bone resorption or formation, duration of the disease, or degree of
      metabolic control. CONCLUSIONS: Although we did not establish decreased LS2-4 and
      FN-BMD measurements in patients with DM1, we found reduced bone formation and
      increased bone resorption markers in children with DM1. Measurements of serum
      osteocalcin, PINP, urinary Ntx and Ca/Cr might be useful for long-term follow-up
      in children and adolescents with DM1.

PMID- 16886589
TI  - Urinary tract infections in children with congenital adrenal hyperplasia.
AB  - OBJECTIVE: To investigate the incidence of urinary tract infections (UTIs) in
      children with congenital adrenal hyperplasia (CAH), and to determine whether
      there was a correlation between UTIs and the timing and type of genital surgery
      in girls. STUDY DESIGN: Medical records of patients with CAH < or = 15 years were
      reviewed. A parent questionnaire regarding history of UTIs was completed.
      RESULTS: Seventy-one patients with classic CAH (41 girls, 30 boys) aged 8.3 +/-
      4.2 years were identified. Thirty-five (85%) girls had undergone feminizing
      genitoplasty at 1.1 +/- 0.8 years, while six (15%) had not. History of UTI was
      reported in nine (12.6%) patients (one boy, eight girls). In seven of the eight
      girls, genital surgery had been performed and all UTIs occurred after surgery.
      One UTI was reported in a girl who had not undergone surgery. No correlation was
      found between UTIs and the type of genital surgery. CONCLUSION: The incidence of
      UTIs in children with CAH is similar to that in the general population. Although
      preliminary, our results do not suggest an increased risk of UTIs if surgery is
      delayed.

PMID- 16886591
TI  - Metformin-diet ameliorates coronary heart disease risk factors and facilitates
      resumption of regular menses in adolescents with polycystic ovary syndrome.
AB  - BACKGROUND: In 35 adolescent females (17 +/- 2 years) with polycystic ovary
      syndrome (PCOS), median body mass index (BMI) 30.8 kg/m2, we assessed effeicacy
      of metformin-diet for 1 year for reduction of weight, insulin, HOMA insulin
      resistance (IR), cholesterol, triglycerides, and resumption of regular menses.
      METHODS: Calories (26% protein, 44% carbohydrate) were targeted to 1,500
      1,800/day if BMI was <25 or to 1,200-1,500/day if BMI was > or = 25, along with
      2,550 mg metformin. RESULTS: Median weight fell from 82.7 to 79.1 kg (p = 0.009),
      insulin 16.7 to 13.3 microU/ml (p <0.0001), HOMA IR 3.41 to 2.74 (p = 0.0004),
      total cholesterol 164 to 151 mg/dl (p = 0.002), and triglyceride 103 to 85 mg/dl
      (p = 0.006). The percentage of cycles with normal menses rose from a pre
      treatment mean of 22% to 74%, p < 0.0001. CONCLUSIONS: In adolescents with PCOS,
      metformin-diet reduces weight, insulin, IR, cholesterol, and triglycerides, and
      facilitates resumption of regular menses.

PMID- 16886590
TI  - Variable deficits of bone mineral despite chronic glucocorticoid therapy in
      pediatric patients with inflammatory diseases: a Glaser Pediatric Research
      Network study.
AB  - OBJECTIVE: To evaluate the relationship between chronic glucocorticoid (GC)
      exposure and bone mineral density (BMD) in children with rheumatic diseases and
      inflammatory bowel disease. STUDY DESIGN: Lumbar spine BMD was measured by DXA in
      86 GC-treated children (66% female, age 8-20 years, mixed ethnicity) screened for
      a multi-center intervention trial. Predictors of spine BMD z-score and vitamin D
      [25(OH)D] were examined by multivariable linear regression. RESULTS: Mean prior
      year and lifetime cumulative GC exposure was 77.8 mg/kg and 224.6 mg/kg,
      respectively. BMD z-scores ranged from -3.7 to 2.2 SD (-1.1 +/- 1.2, mean +/-
      SD). Lower BMD z-scores were associated with increased prior year average daily
      GC dose (p = 0.03), decreased height z-score (p = 0.003), and decreased 25(OH)D
      concentrations (p = 0.03), but explained only a small proportion of BMD
      variability (adjusted R2 = 0.29). The 25(OH)D levels were <20 ng/ml in 45% of
      patients, and low 25(OH)D was associated with non-Caucasian ethnicity (p <0.001),
      increased age (p = 0.004), increased parathyroid hormone (p = 0.03), and residing
      in the Boston area (p <0.001). CONCLUSIONS: Although GC exposure is significantly
      associated with BMD z-score, the association is too variable to serve as a
      consistent predictor of reduced BMD in children. Vitamin D insufficiency is
      common and may contribute to skeletal deficits in this population.

PMID- 16886592
TI  - Diurnal salivary cortisol concentration in school-aged children: increased
      morning cortisol concentration and total cortisol concentration negatively
      correlated to body mass index in children with recurrent abdominal pain of
      psychosomatic origin.
AB  - INTRODUCTION: The sampling method for salivary cortisol is sensitive, specific
      and pain-free. Our knowledge about cortisol concentration in saliva and plasma in
      school-aged children is sparse and contradictory. AIM: To estimate diurnal
      variation in salivary cortisol concentration in children with and without
      psychosomatic recurrent abdominal pain (RAP), and to compare groups and relate
      the concentrations to age, sex, puberty, body mass index (BMI), allergy, headache
      and ethnicity. CHILDREN AND METHOD: Saliva was collected in 'Salivette' tubes
      from 159 healthy girls and 147 healthy boys, aged 5-15 years, and from 25 girls
      and 6 boys, aged 6-18 years, with RAP of psychosomatic origin, at 08.00 h, 13.00
      h and 20.00 h. Saliva was analysed using a commercial RIA-cortisol kit. RESULTS:
      The median concentrations in healthy girls and boys were 8.8/8.3 nmol/l at 08.00
      h, 5.5/5.3 nmol/l at 13.00 h, and 2.1/2.3 nmol/l at 20.00 h, respectively.
      Cortisol concentrations differed between 6-7 year-old and 9 year-old children
      (higher in the former). Age-matched post-menarcheal girls had higher cortisol
      concentrations in the evening, 2.2 vs 1.7 nmol/l (p = 0.03). The results were
      independent of BMI, headache and allergy. In the RAP group, diurnal cortisol
      concentrations in girls/boys at the different time-points were 14.8/12.9,
      5.2/5.8, and 2.4/2.7 nmol/l, respectively, and were negatively correlated to BMI.
      Total secretion of cortisol was higher than in healthy children. Cortisol
      concentration was independent of allergy, headache and ethnicity, CONCLUSION: In
      healthy children, salivary cortisol concentration was dependent on time, age and
      menarche. In children with RAP of psychosomatic origin, morning and total
      secretion of cortisol were significantly higher than in healthy children and
      negatively correlated to BMI.

PMID- 16886593
TI  - Combination growth hormone and gonadotropin releasing hormone analog therapy in
      11beta-hydroxylase deficiency.
AB  - Diagnosis of 11beta-hydroxylase deficiency was made in a boy at the age of 2 1/2
      years on the basis of peripheral precocious puberty, growth acceleration (height
      standard deviation score +4.4) with advanced skeletal maturation (bone age 8.4
      years) and elevated deoxycortisol levels. Glucocorticoid supplementation led to
      normalization of blood pressure but was associated with progression to central
      precocious puberty and increase in bone age resulting in decrease in predicted
      adult height to 133.7 cm (target height 163 cm). The child was started on GnRH
      analog (triptorelin 3.75 mg every 28 days), which led to improvement in predicted
      adult height by 3.1 cm over 15 months. Addition of growth hormone (0.1 IU/kg/day)
      resulted in improvement in predicted adult height (151 cm) and height deficit (12
      cm) over the next 3.6 years. Final height (151 cm) exceeded predicted height at
      the initiation of GnRH analog treatment by 17.3 cm. This report suggests that
      combination GH and GnRH analog treatment may be useful in improving height
      outcome in children with 11beta-hydroxylase deficiency and compromised final
      height.

PMID- 16886594
TI  - Transient neonatal hyperparathyroidism: a presenting feature of mucolipidosis
      type II.
AB  - The phenotype of mucolipidosis type II (ML II), a disorder of lysosomal enzyme
      transport, includes mucopolysaccharidosis type I (Hurler syndrome)-like features
      and dysostosis multiplex, usually apparent after 6 months of age. We describe
      here the natural history of neonatal hyperparathyroidism, a recently described
      presentation of ML II. A female neonate presented with multiple fractures and
      radiological features of osteopenia and 'rickets-like' changes. Longitudinal
      evaluation, while the patient was treated with vitamin D 800-3,000 IU/day orally,
      indicated secondary hyperparathyroidism which resolved, biochemically and
      radiologically, by age 4 months. Neonatal hyperparathyroidism in ML II is severe,
      transient, and probably secondary to impaired placental calcium transport,
      simulating a condition observed in the offspring of chronically hypocalcemic
      mothers.

PMID- 16886595
TI  - Modulating ICBP90 to suppress human ribonucleotide reductase M2 induction
      restores sensitivity to hydroxyurea cytotoxicity.
AB  - BACKGROUND: Ribonucleotide reductase (RR) inhibition by hydroxyurea (HU) causes
      deoxyribonucleotide (dNTP) depletion, which activates the replication checkpoint,
      a part of the S-phase checkpoint that responds to DNA damage by inhibiting late
      origin firing. It also transactivates RR and other genes involved in DNA
      replication and repair. ICBP90 (overexpressed in breast cancer) is a novel Rb
      associating transactivator for the human topoisomerase IIalpha gene and responds
      to DNA damage-induced checkpoint signaling. MATERIALS AND METHODS: ICBP90
      expression was monitored by Western blot. Promoter activity was detected via the
      luciferase assay and gene silencing via siRNA. Cell death was monitored by the
      MTT assay. RESULTS: dNTP depletion by HU induced ICBP90, ICBP90 transactivated
      RR's M2 subunit gene, and ICBP90 induction was necessary for HU-induced M2
      accumulation. Blocking the M2 accumulation via anti-ICBP90 siRNA caused greater
      sensitivity in HU-resistant human cancer. CONCLUSION: A transcriptional
      intervention strategy is presented through which HU-resistant cancers may be
      eradicated without dose escalation.

PMID- 16886597
TI  - Comparison of ID8 MOSE and VEGF-modified ID8 cell lines in an immunocompetent
      animal model for human ovarian cancer.
AB  - Attempts to develop novel immunotherapeutic mouse models have been hampered by
      the lack of an adequate in vivo system. This study was performed to establish an
      immunocompetent mouse model for the testing of immunotherapy concepts. The in
      vivo system was based on a svngeneic mouse ovarian surface epithelium (MOSE)
      cancer, physiologically and biologically closely resembling human epithelial
      ovarian cancer. In addition, a more aggressive variant containing a mutated form
      of vascular epithelial growth factor was also evaluated. The growth patterns of
      these ovarian cancer cells in mice were compared to the established, highly
      aggressive 4T1 breast cancer model. A clinically-relevant tool for the study of
      different growth patterns in ovarian cancer, with potential significance for the
      development of novel immunological methods, was successfully developed.

PMID- 16886596
TI  - Concomitant cell growth and differentiation are dependent on erbB1 and integrin
      activation in an autonomously surviving colon adenocarcinoma: involvement of
      autocrine amphiregulin secretion.
AB  - In normal colon epithelium, cell proliferation is followed by cell
      differentiation. The purpose of this work was to investigate, in the HT29-D4
      colon adenocarcinoma cell line, the occurrence of a temporal sequence of changes
      in cell proliferation and differentiation, the role of autocrine EGF family
      ligands and to determine which transduction pathway(s) are involved in these
      processes. In a medium lacking both growth factor and serum, HT29-D4 cells
      secreted amphiregulin (AR), which was shown to be strongly involved in cell
      adhesion, growth and differentiation. In the main, integrins alpha2beta1 and
      alphavbeta6 intervened in these processes. Using tyrphostins, it was demonstrated
      that AR involvement was mediated through the ErbB1/ERK1,2 and ErbB1/FAK pathways.
      These signalling molecules were directly involved in pRb inhibition and, thus, in
      cyclin A expression. Concomitantly, colon differentiation markers were also
      expressed. Furthermore, terminal cell maturation resulted in a colon absorptive
      cell with strong polarisation, the growth of which was inhibited by tyrphostin
      and an ERK1,2 inhibitor. It was concluded that in a colon adenocarcinoma, cell
      proliferation and differentiation can occur concomitantly and that these
      deregulated processes are controlled by autocrine secretion through the
      ErbB1/ERK1,2 and FAK pathways.

PMID- 16886598
TI  - Antiproliferative and proapoptotic activities of pyranoxanthenones,
      pyranothioxanthenones and their pyrazole-fused derivatives in HL-60 cells.
AB  - BACKGROUND: Synthetic pyranoxanthenones, pyranothioxanthenones and their pyrazole
      fused derivatives, which bind to DNA, block the G2 + M-phases of the cell cycle
      and inhibit the proliferation of ascitic and solid tumor cell lines in vitro,
      were tested for their ability to induce apoptosis in the HL-60 cell system.
      MATERIALS AND METHODS: Various markers of tumor cell metabolism, apoptosis
      induction and mitochondrial permeability transition (MPT) were assayed in vitro
      to evaluate drug cytotoxicity. RESULTS: All these compounds, and especially the
      pyrazole-fused pyranoxanthenones 7, 8 and 10, which were effective in the 3-5
      microM range and were more potent than the pyranoxanthenones, reduced the
      proliferation of HL-60 cells at 2 and 4 days. These antitumor drugs inhibited DNA
      synthesis at 2 h in relation to their ability to block the cellular uptake of
      purine and pyrimidine nucleosides within 15 min. Internmucleosomal DNA
      fragmentation, a late marker of apoptosis, was induced in a concentration
      dependent manner by 7 and 10 at 24 h. Poly(ADP-ribose) polymerase-1 (PARP-1)
      cleavage, an early event required for cells committed to apoptosis, was detected
      within 12 h in HL-60 cells treated with 7 and 10. In accord with the fact that
      the caspase cascade is responsible for PARP-1 cleavage, 7 and 10 induced the
      activities of initiator caspases-2 and -9 and effector caspase-3 within 9 h in HL
      60 cells. The release of mitochondrial cytochrome c (Cyt c) was also detected
      within 9 h in HL-60 cells treated with 7 and 10, consistent with the fact that
      Cyt c is the apoptotic trigger that activates caspase-9. However, 7 and 10
      neither caused the rapid collapse of mitochondrial transmembrane potential, nor
      the mitochondrial swelling linked to MPT. CONCLUSION: Pyrazole-fused
      pyranoxanthenones are DNA-interacting antiproliferative drugs that do not
      directly target mitochondria in cell and cell-free systems to induce the
      intrinsic pathway of apoptosis.

PMID- 16886599
TI  - Activation of Akt and mTOR in CD34+/K15+ keratinocyte stem cells and skin tumors
      during multi-stage mouse skin carcinogenesis.
AB  - BACKGROUND: The goal of the present studies was to localize two proteins known to
      be involved in regulation of cell proliferation and survival in specific cell
      populations in normal SENCAR mouse skin and during multi-stage skin
      carcinogenesis. The proteins evaluated included activated Akt, as defined by
      phosphorylation of Akt at Serine-473 (pAkt) and mammalian target of rapamycin
      (pmTOR), defined by phosphorylation of mTOR at Serine-2448 (pmTOR). The cell
      populations examined included mouse keratinocyte stem cells (KSCs) within hair
      follicles and preneoplastic papilloma cells. MATERIALS AND METHODS:
      Immunochemical staining analysis as well as triple color immunofluorescence in
      combination with confocal microscopy were used to evaluate the presence of
      activated Akt and mammalian target of rapamycin (mTOR) in KSCs within the bulge
      niche of hair follicles, as identified by expression of the specific markers of
      mouse KSCs, CD34 and cytokeratin 15 (K15). Western blot analysis was used to
      examine CD34 and K15 protein levels in dorsal skin isolated from SENCAR mice
      during multi-stage skin carcinogenesis. RESULTS: CD34+/K15+ KSCs were located
      only in the outer root sheath (ORS) of a specific niche within hair follicles
      defined as "the bulge". The location of CD34+/K15+ KSCs remained restricted to
      the bulge region throughout the 22-week time-period examined during which pre
      malignant papillomas developed and rapidly expanded. There was a significant
      decrease in K15 protein levels at 24 h and 15 weeks in dorsal skin treated with
      DMBA/TPA compared to CD34 protein levels. CD34+ cells within the numerous hair
      follicles in hyperplastic skin were found to undergo proliferation during the
      process of multi-stage skin carcinogenesis based on their staining with
      antibodies directed against proliferating cell nuclear antigen (PCNA). While pAkt
      was present within the bulge region of hair follicles, pmTOR was present in cells
      in the ORS of the bulge region as well as the upper infundibulum of hair
      follicles in dorsal skin treated with acetone. Within papillomas tissues isolated
      at 15 weeks following DMBA/TPA treatment, pAkt was localized to suprabasal cells
      with nominal staining of pAkt in the basal cell layer. There were fewer cells
      within the basal cell layer that contained pmTOR, in addition to the presence of
      pmTOR in suprabasal cells within papillomas. CONCLUSION: These results provide
      first time evidence for pAkt and pmTOR in CD34+/K15+ KSCs localized to the outer
      root sheath niche of the bulge region of mouse hair follicles. Taken together,
      the present observations suggest that pAkt and pmTOR may allow this cell
      population to evade terminal differentiation and to persist for long periods of
      time in their specific niche. Strategies that target pAkt and pmTOR may deplete
      both cells within the CD34+/K]5+ KSCs compartment, as well as impacting the
      survival of nonproliferating suprabasal cells within pre-malignant papillomas.

PMID- 16886600
TI  - Establishment and characterization of amylase-producing lung adenocarcinoma cell
      line, IMEC-2.
AB  - BACKGROUND: Few studies have successfully established an amylase-producing lung
      cancer cell line or have examined its cytological, biochemical and biological
      features. PATIENTS AND METHODS: Cancer cells, isolated from pleural effusion
      using a gradient method, were cultivated. RESULTS: Amylase production from the
      newly established cell line was confirmed by positive staining for alpha-amylase
      and increased amylase levels in the culture supernatant. Electron microscopy
      revealed zymogen granule-like structures. Sialylation of salivary-type amylase
      was confirmed directly from the cell line by examining the neuraminidase
      sensitivity and amylase elution profile under high-performance liquid
      chromatography. Neither EGFR or KRAS mutation were found. CONCLUSION: This cell
      line offers a useful tool for analyzing the pathogenesis and pathophysiology of
      amylase-producing lung cancers. Moreover, it might be useful for probing the
      metastasis and invasiveness of lung cancer cells and for developing an early
      diagnostic method based on sialylated salivary-amylase production.

PMID- 16886601
TI  - Reduced expression level of mgmt mRNA and beta-catenin gene mutation in rat colon
      tumors.
AB  - BACKGROUND: O6-methylguanine-DNA methyltransferase (MGMT) is a DNA repair protein
      and protects DNA from the biological effects of alkylating carcinogens. The
      purpose of this study was to investigate the association between the mRNA
      expression level of the Mgmt gene and mutation of the beta-catenin gene in rat
      colon tumors induced by azoxymethane (AOM) plus dextran sulfate sodium (DSS).
      MATERIALS AND METHODS: Eleven tumor samples from rat colon treated by AOM plus
      DSS were examined. Mutation of the beta-catenin gene was identified by polymerase
      chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis. The
      expression level of Mgmt mRNA was determined by reverse transcription-PCR (RT
      PCR). RESULTS: Four out of five adeno-carcinoma samples bearing beta-catenin gene
      mutation (5 out of 11, 45%) displayed a decrease in expression levels of Mgmt
      mRNA (p<0.02). CONCLUSION: These results suggest that the reduced expression of
      Mgmt mRNA and beta-catenin gene mutation may contribute to the development of rat
      colon tumors.

PMID- 16886602
TI  - Allelic status of chromosomes 17p, 18q, 22q [corrected] 3p and their clinical
      usefulness in colorectal cancer.
AB  - BACKGROUND: To determine whether the allelic status of chromosomes is clinically
      useful in colorectal cancer, the allelic losses at chromosomes 17p, 18q, 22q and
      3p and their relationships with the clinicopathological features in colorectal
      cancer (CRC) patients, who had undergone curative surgery without adjuvant
      chemotherapy, were examined. MATERIALS AND METHODS: The allelic status at 17p,
      18q, 22q and 3p was analyzed by PCR-SSCP (polymerase chain reaction single-strand
      conformation polymorphism) in 139 CRC from patients who had undergone curative
      surgery between October 1994 and June 1996. The relationships between these
      allelic losses and the clinicopathological features were investigated. RESULTS:
      The lymph node status was significantly associated with the allelic status of
      17p, 18q and 22q. The tumor site and tumor differentiation were significantly
      associated with the allelic status of 18q. When patients with more than two
      allelic losses were defined as the high allelic loss group and those with no, or
      only one allelic loss were defined as the low allelic loss group, it was found
      that the lymph node involvement was significantly higher in the high than in the
      low allelic loss group. Only three out of 25 patients in the low allelic loss
      group had lymph node metastasis, and 15 patients in this group without lymphatic
      invasion had no lymph node metastasis. There was no relationship between the
      allelic status and survival at any stage. CONCLUSION: The allelic status was
      significantly associated with lymph node metastasis. A combination of allelic
      status and lymphatic invasion assessment can predict the lymph node status before
      radical surgery.

PMID- 16886603
TI  - First in vivo evaluation of liposome-encapsulated 223Ra as a potential alpha
      particle-emitting cancer therapeutic agent.
AB  - BACKGROUND: Liposomes carrying chemotherapeutics have had some success in cancer
      treatment and may also be suitable carriers for therapeutic radionuclides. This
      study was designed to evaluate the biodistribution and to estimate the radiation
      doses of the alpha emitter 223Ra loaded into pegylated liposomes in selected
      tissues. MATERIALS AND METHODS: 223Ra was encapsulated in pegylated liposomal
      doxorubicin (PLD) by ionophore-mediated loading. The biodistribution of liposomal
      223Ra was compared to free cationic 223Ra in Balb/C mice. RESULTS: Liposomal
      223Ra circulated in the blood with an initial half-life in excess of 24 hours,
      which agreed well with that reported for PLD in rodents, while the blood half
      life of cationic 223Ra was considerably less than an hour. When liposomal 223Ra
      was catabolized, the released 223Ra was either excreted or taken up in the
      skeleton. This skeletal uptake increased up to 14 days after treatment, but did
      not reach the level seen with free 223Ra. Pre-treatment with non-radioactive PLD
      4 days in advance lessened the liver uptake of liposomal 223Ra. Dose estimates
      showed that the spleen, followed by bone surfaces, received the highest absorbed
      doses. CONCLUSION: Liposomal 223Ra was relatively stable in vivo and may have
      potential for radionuclide therapy and combination therapy with chemotherapeutic
      agents.

PMID- 16886605
TI  - Prostaglandin E2 receptor subtype 2 (EP2) null mice are protected against murine
      lung tumorigenesis.
AB  - BACKGROUND: Manipulating prostaglandin (PG) production modulates tumor
      development. Elevated PGI2 production prevents murine lung cancer, while
      decreasing PGE2 content protects against colon cancer. PGE2 receptor subtype 2
      (EP2) -deficient mice were hypothesized to be resistant to lung tumorigenesis.
      MATERIALS AND METHODS: EP2 null BALB/c mice and their wild-type littermates were
      exposed to an initiation-promotion carcinogenesis protocol and lung tumorigenesis
      was examined. Chronic lung inflammation was induced to determine whether EP2
      ablation influenced inflammatory cell infiltration. RESULTS: Tumor multiplicity
      in EP2 null mice was 34% lower than in their wild-type littermates (21.9+/-3.0
      vs. 14.5+/-2.9 tumors/mouse, p<0.001). The lung tumor burden, an indicator of
      growth rate, also declined (57%, p<0.05). All the mice exhibited similar
      inflammatory cell infiltration. CONCLUSION: PGE2, acting through EP2, enhanced
      lung tumorigenesis through a mechanism that may be distinct from its
      proinflammatory activity. Thus, EP2 is a potential target for novel
      chemoprevention strategies.

PMID- 16886604
TI  - Decrease of telomeres and increase of interstitial telomeric sites in chromosomes
      of short-term cultured gastric carcinoma cells detected by fluorescence in situ
      hybridization.
AB  - BACKGROUND: Deletion or shortening of chromosomal telomeres is associated with
      cellular aging and carcinogenesis. Telomeric sites are interstitially located in
      chromosomes. To clarify the frequency of telomerase abnormalities in cancer and
      their relationship with any characteristics of gastric carcinomas, telomeric
      aberrations in eleven cultured specimens of human gastric cancer were
      investigated by cytogenetic analysis. MATERIALS AND METHODS: Chromosomal
      metaphase specimens, obtained by primary culture of cells from surgical specimens
      of eleven gastric cancer patients, were examined by fluorescent in situ
      hybridization (FISH) using all telomeric and chromosome 17 specific-telomeric DNA
      probes. The number of telomeric signals and interstitial telomeric signals (ITS)
      were counted. DNA ploidy was examined by flow cytometry. RESULTS: The mean
      telomere signal per nucleus (MTS) observed in peripheral blood lymphocytes (PBLs)
      of normal volunteers (n=10) was 71.3+/-3.9%. The MTS in the carcinoma cells
      (46.9+/-2.6%) was significantly lower than in PBLs (p<0.01). Although ITS were
      not observed in PBLs, the mean rate of ITS was 41.2+/-22.0%, and the mean rate of
      ITS per chromosome was 2.1+/-2.1% in the cancer specimens. In DNA aneuploid
      carcinoma cells, the MTS was significantly lower, the mean rate of ITS tended to
      be higher (p=0.072), and the mean rate of ITS per chromosome was significantly
      higher (p<0.05), than in DNA diploid lymphocytes. Histologically, the mean rate
      of ITS per chromosome in carcinomas with venous infiltrations was significantly
      greater than in those without (p<0.05). CONCLUSION: Deletion and interstitial
      translocation of telomeric loci of chromosomes were frequent alterations in
      gastric carcinoma cells and increased numbers of interstitial telomeric signals
      were associated with venous invasion.

PMID- 16886606
TI  - The predominant CD44 splice variant in prostate cancer binds fibronectin, and
      calcitonin stimulates its expression.
AB  - BACKGROUND: Prostate cancer (PC) consistently overexpresses variant the (v)
      isoform of the cell adhesion protein CD44, and loses expression of the standard
      (s) isoform. MATERIALS AND METHODS: We re-expressed CD44 full-length (exons 1-20)
      or standard (exons 1-5 + 16-20) or enforced stable RNAi against CD44v, and the
      examined functional effects on PC. The effect of stable knockout of calcitonin, a
      paracrine factor, or its receptor, on CD44 was assessed. RESULTS: Re-expression
      of full-length CD44 or CD44s increased the total CD44 mRNA and CD44s protein
      while suppressing CD44v. These approaches, and RNAi to CD44v, decreased invasion.
      In adhesion assays, benign prostate cells bound mainly to hyaluronan, whereas PC
      lost affinity for hyaluronan but bound more strongly to fibronectin. Re
      expressing CD44s restored predominant hyaluronan binding. Knockout of the
      calcitonin receptor in PC-3 derived cells caused marked loss of CD44v expression
      and reversion to CD44s expression. CONCLUSION: Calcitonin influenced PC's balance
      between CD44s and CD44v. CD44v controlled invasiveness, altered ligand binding,
      and provides a target for therapeutic intervention.

PMID- 16886607
TI  - Germ line insertions of moloney murine leukemia virus in the TLL mouse causes
      site-specific differences in lymphoma/leukemia frequency and tumor
      immunophenotype.
AB  - BACKGROUND: Moloney murine leukemia virus (Mo-MLV) has proven valuable for
      studies of the pathogenesis of malignant lymphoma. Inoculation of newborn mice
      induces T cell lymphoma with 100% incidence. The TLL (T cell lymphoma/leukemia)
      strain was previously established and was shown to spontaneously develop T cell
      lymphoma at high frequency. MATERIALS AND METHODS: Differential screening of cDNA
      libraries was performed to discover an involvement of Mo-MLV and genomic
      sequencing was used to identify the chromosomal position of Mo-ML V proviral
      integration sites. Immunophenotypes of the tumors were established by flow
      cytometty. Disease frequency curves were created according to the Kaplan-Meier
      method. RESULTS: Two independent Mo-MLV germ line integrations were characterized
      on chromosomes 2 and 14, giving rise to two substrains of mice denoted TLL-2 and
      TLL-14. The chromosomal position of the integrated provirus affected the
      frequency of disease, as well as the immunophenotype of the tumors. CONCLUSION:
      The data suggest that factors influencing the transcriptional activity of the
      chromosomal regions, leading to differences in proviral expression, could
      underlie the observed difference in tumor frequency.

PMID- 16886609
TI  - Quantitative structure-cytotoxicity relationship analysis of coumarin and its
      derivatives by semiempirical molecular orbital method.
AB  - A semiempirical molecular orbital method (CAChe) was applied to delineate the
      relationship between cytotoxicity against the human squamous cell carcinoma line
      HSC-2 (evaluated by 50% cytotoxic concentration, CC50) of 20 coumarin (2H-pyran-2
      one) derivatives and twelve physical parameters (descriptors) calculated by the
      CONFLEX/PM3 method. There was a highly significant correlation between the CC50
      and ionization potential, highest occupied molecular orbital (HOMO) energy,
      difference between electron energy of HOMO and electron energy of lowest
      unoccupied molecular orbital (LUMO), or absolute hardness (r2=0.756 - 0.802). On
      the other hand, there was no significant correlation between the CC50 and heat of
      formation, stability of hydration, dipole moment, electron affinity, or LUMO
      energy (r2=0.13.- 0.36). When the CC50 was plotted vs. log P, a parabolic curve
      was produced, with a maximum cytotoxicity (or the least CC50 value) at log P of
      2.5. The present study demonstrated that hardness and softness, other than the
      electron accepting and donating properties, are important factors in estimating
      the cytotoxic activity of coumarin derivatives.

PMID- 16886608
TI  - Association of the methylenetetrahydrofolate reductase polymorphism in Korean
      patients with childhood acute lymphoblastic leukemia.
AB  - BACKGROUND: Methylenetetrahydrofolate reductase plays a central role in
      converting folate to methyl donor for DNA methylation. Recently,
      methylenetetrahydrofolate reductase (MTHFR C677T and A1298C) mutations were
      discovered to be associated with childhood acute lymphoblastic leukemia (ALL), as
      well as colon cancer, lymphoma, esophageal and stomach cancer. Therefore, it was
      hypothesized that the MTHFR polymorphisms are associated with the risk of
      childhood ALL in the Korean population. PATIENTS AND METHODS: DNA samples taken
      from 66 patients with ALL and 100 age-matched controls were analyzed using the
      polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)
      assay for detection of MTHFR C677T and A1298C mutations. RESULTS: The frequency
      of the AC genotype for MTHFR A1298C polymorphism was significantly different
      between the controls and the cases (OR, 2.22; CI, 95% 1.09-4.51, p=0.03). The
      1298AC+CC genotype was also significantly different (OR, 2.11; 95% CI, 1.06-4.22;
      p=0.049). There was, however, no significant difference for MTHFR C677T
      polymorphism and combined genotype frequencies between the two groups.
      CONCLUSION: Although no consistent results on associations between MTHFR A 1298C
      polymorphism and ALL in the populations studied were obtained, the A1298C
      polymorphism, at least in Koreans, may be a genetic determinant among childhood
      ALL patients.

PMID- 16886610
TI  - Experimental model and immunohistochemical analyses of U87 human glioblastoma
      cell xenografts in immunosuppressed rat brains.
AB  - BACKGROUND: To study the neuropathology and selected tumour markers of malignant
      gliomas, an animal glioma model was developed using the implantation of human
      glioblastoma clone U87 into rat brains. MATERIALS AND METHODS: The U87 cell
      suspension, or precultured U87 tumour spheroids, were inoculated into the brain
      of 4-week-old cyclosporin A immunosuppressed Wistar rats. The resulting first
      generation tumours were then transferred, through serial transplantations to
      rats, to obtain second and third generation tumours. Brain tumour sections were
      examined for various known tumour markers by routine HE staining and
      immunohistochemical analyses. RESULTS: The immunohistochemical analyses showed
      that p53, S100 protein, glial fibrillary acidic protein (GFAP) and synaptophysin
      expressions, initially present in the tissue culture, were gradually lost in
      later tumour generations, whereas nestin and musashi expressions increased,
      possibly indicating progressive tumour cell dedifferentation. Persistent
      kallikrein, CD68 and vimentin expressions in U87 cells, as well as in all the
      generations of tumours, may be related to the preservation of the mesenchymal
      cell phenotype in this tumorigenesis model. Decreased cathepsins expression
      indicated lower invasive potential, but increasing Ki-67 expression marked higher
      proliferation activity in the subsequent tumour generations. The strong immune
      reaction for FVIII in the second and third generation tumours correlated with the
      observed increase in vascular proliferation in these tumours. CONCLUSION: A
      simple, and well-defined rat model of fast-growing glioma was established,
      providing a basis for further experimental studies of genetic and protein
      expression fingerprints during human glioma tumorigenesis.

PMID- 16886611
TI  - Expression of Smad4 and TGF-beta2 in colorectal carcinoma.
AB  - BACKGROUND: TGF-beta, a potent natural antiproliferative agent, is believed to
      play an important role in suppressing tumorigenicity. This effect is mediated
      through Smad4, a tumour-suppressor gene, at chromosome 18q21, which affects gene
      transcription and controls cell growth. The aim of the study was to investigate
      the expression of Smad4 and TGF-beta2 in colorectal carcinomas and to correlate
      them with pathological parameters and patient survival. MATERIALS AND METHODS:
      Formalin-fixed paraffin-embedded tissue from 49 cases of colon carcinoma was
      stained by immunohistochemistry for TGF-beta2 and Smad4 protein. RESULTS: Smad4
      nuclear and cytoplasmic staining was absent in 9/49 (18.3%) or reduced in 18/49
      (36. 7%) colorectal carcinoma, while in the remaining 22 (44.8%) Smad4 expression
      comparable with colonic mucosa was observed. TGF-P2 cytoplasmic staining was
      expressed in all cases and was overexpressed in 24/49 (48.9%) carcinoma. A
      statistically significant correlation was found between Smad4 expression and
      tumour grade (p =0.02) and between TGF-beta2 expression and Dukes' stage
      (p=0.03). A slight tendency for a relationship between Smad4 and TGF-beta2
      (p=0.25) was also observed. No statistically significant relationship between the
      above markers and survival was detected. CONCLUSION: In poorly-differentiated
      carcinoma, Smad4 protein expression was retained and may be linked to TGF-beta2
      overexpression, due to the activation or deregulation of the TGF-fl signalling
      pathway. Inactivation of the TGF-beta gene occurs at an early stage of colorectal
      carcinogenesis, while inactivation of Smad4 is probably a late event.

PMID- 16886612
TI  - C-MYC locus amplification as metastasis predictor in intestinal-type gastric
      adenocarcinomas: CGH study in Brazil.
AB  - BACKGROUND: The genetic events involved in gastric cancer, the third most
      frequent cancer in the world with a high incidence in Pard State, Brazil, remain
      largely unknown. MATERIALS AND METHODS: Twenty-one primary gastric
      adenocarcinomas were investigated by comparative genomic hybridization (CGH) and
      the relationships between genomic abnormalities and histopathological features
      were evaluated. RESULTS: Eighty-one percent of cases presented DNA copy-number
      changes. Chromosomal gains were the most frequent finding, losses occurring only
      in the diffuse type. The main copy-number gains were on chromosome 8, principally
      on 8q24.1 (8/21 cases), 8p21 (3/21) and 8p23.2-8p12 (2/21). Gain of region 8q24.
      1, where C-MYC is located, was the main finding, exclusively in the intestinal
      type with metastasis. CONCLUSION: C-MYC locus amplification may be predictor of
      aggressiveness in intestinal-type gastric cancer, playing an important role in
      its development and progression. Moreover, other genes on 8q24 should be
      investigated. Gastric adenocarcinomas of differing histopathological features
      were associated with distinct genetic alterations, supporting the hypothesis that
      they evolve through distinct genetic pathways.

PMID- 16886613
TI  - Preventive effect of ortho dimer of butylated hydroxyanisole on activator protein
      1 activation and cyclooxygenase-2 expression in macrophages stimulated by
      fimbriae of Porphyromonas gingivalis, an oral anaerobe.
AB  - Butylated hydroxyanisole (BHA; a mixture of 2- and 3-BHA) is widely used as a
      potent antioxidant, but is reported to have adverse effects, such as
      carcinogenesis and pro-inflammatory activity, possibly due to the pro-oxidant
      property of this compound. 2-Methoxyphenol dimers derived from ferulic acid were
      recently demonstrated to inhibit the expression of lipopolysaccharide-stimulated
      cyclooxygenase-2 (COX-2) via redox-sensitive transcription factors such as
      nuclear factor kappa B or activator protein-1 (AP-1), due to a weakening of its
      pro-oxidant property by dimerization. To develop anti-inflammatory and/or
      anticancer drugs for the prevention of oral diseases, such as leukoplakia and
      destructive chronic periodontitis, whether 2-BHA (2-tert-butyl-4-methoxyphenol)
      and its synthetic ortho dimer, bis-BHA (3,3'-di-tert-butyl-5,5'-dimethoxy-1,1'
      biphenyl-2,2'-diol) can inhibit AP-1 transcriptional activity stimulated by
      Porphyromonas gingivalis fimbriae was examined. The fimbria-stimulated AP-1
      activation of RAW 264.7 murine macrophages was markedly inhibited by bis-BHA.
      However, BHA showed slight inhibition. Furthermore, bis-BHA significantly
      inhibited fimbria-induced COX-2 gene expression, which is closely involved with
      inflammation and carcinogenesis. These findings suggest that bis-BHA may possess
      a potent anti-inflammatory effect against oral diseases.

PMID- 16886614
TI  - Inhibition of NO production in LPS-stimulated mouse macrophage-like cells by
      trihaloacetylazulenes.
AB  - The effects of 26 trihaloacetylazulene derivatives on nitric oxide (NO)
      production by the mouse macrophage-like Raw 264.7 cells was investigated. The
      trichloroacetylazulenes [1b-13b] generally showed higher cytotoxicity as compared
      with the corresponding trifluoroacetylazulenes [1a-13a]. All the compounds
      inhibited NO production by lipopolysaccharide (LPS)-activated Raw 264.7 cells to
      various extents. 3-Trifluoroacetylguaiazulene [8a], 1-trifluoroacetyl-4,6,8
      trimethylazulene [10a], 3-methyl-l-trichloroacetylazulene [2b] and 3-ethyl-1
      trichloroacetylazulene [3b] showed lower cytotoxic activity and most effectively
      inhibited NO production. Western blot analysis revealed that compounds [8a, 1Oal
      dose-dependently reduced the intracellular concentration of inducible NO synthase
      (iNOS), whereas compounds [2b, 3b] only marginally affected the iNOS protein
      expression. RT-PCR analysis showed that compounds [8a, 2b] reduced the iNOS mRNA
      expression by approximately 50%. These compounds affected cyclooxygenase-2
      protein and mRNA expression, depending on the concentrations. ESR spectroscopy
      revealed that compounds [8a, 10a, 2b, 3b] neither produced radical, nor scavenged
      NO, superoxide anion or diphenyl-2-picrylhydrazyl radicals. The present study
      showed the inhibitory effects of trifluoroacetylazulenes and
      trichloroacetylazulenes on NO production by activated macrophages.

PMID- 16886615
TI  - Preliminary study of chemosenstivity tests in osteosarcoma using a histoculture
      drug response assay.
AB  - BACKGROUND: The clinical efficacy of chemotherapy is strongly correlated with the
      histoculture drug response assay (HDRA) in various types of cancers. However,
      there have been no previous reports on its use in osteosarcoma. MATERIALS AND
      METHODS: Thirty-six fresh samples of human osteosarcoma were evaluated by the
      HDRA method in order to determine its possible usefulness in the treatment of
      this cancer. All the materials were obtained either during biopsy or surgical
      excision at our hospital, between January 2003 and October 2005. RESULTS: A
      significant inhibition rate in primary biopsies was observed with Adriamycin
      (ADM) (47.3+/-15.3%); Cisplatin (CDDP) (36.3+/-22.3%); and Carboplatin (CBP)
      (50.5+/-23.3%); treatment. ADM and CBP demonstrated a statistically significant
      increase in inhibition rates compared to the other drugs. CONCLUSION: Even though
      the HDRA method has many limitations, it might be a feasible and useful technique
      for selecting and predicting the efficacy of anticancer drugs for osteosarcoma
      patients.

PMID- 16886616
TI  - Predicting tumor cell repopulation after response: mathematical modeling of
      cancer cell growth.
AB  - The kinetics of regrowth of tumor cells after treatment may offer a new end-point
      for clinical trials. Based on our testing, it is best described in this manner:
      y(t) = a*exp(-b*t) + c*exp(d*t). Human malignant glioma cells U87 MG were treated
      with etoposide and allowed to regrow after treatment. The cell number versus time
      data were fitted mathematically to the two-term exponential model. Parameters b
      and d were independent of the drug concentration, while a increased c decreased
      as the drug dose increased. The concentration independence of b and d indicated
      that both cell proliferation and cell death kinetics were independent of the drug
      treatment, which suggests constant times for cell cycle and apoptosis. The
      concentration dependence of c suggests that the time until the cells started
      regrowing depended on the treatment, repair mechanisms taking longer after heavy
      damage. The two-term exponential model predicted tumor repopulation in this in
      vitro system. These results indicated that the velocities of the logarithm of
      cell growth and cell death were independent of drug treatment, while the recovery
      time of the tumor repopulation was dependent on the drug dose. The two-term
      exponential model can be used to predict tumor repopulation in an in vitro system
      and this model will be further tested using clinical data.

PMID- 16886617
TI  - Histamine and selenium in lung cancer.
AB  - The relationship between allergies and cancer incidence and the role played by
      histamine on the immune system and on inhibiting tumor growth have been the
      subject of study in our group. The influence of histamine dosage on free radicals
      was investigated in both lung cancer and healthy subjects. Plasmatic selenium
      levels in the same patients were assayed in order to highlight the role played by
      free radicals in lung cancer. The role of selenium on the genesis of lung cancer
      is well known. Thirty-seven male patients with lung adenocarcinoma or squamous
      carcinoma were tested. The control group included thirty-nine healthy male
      subjects. The results indicated a significant decrease in histamine plasma levels
      in subjects with cancer (p=0.0038) compared to the healthy subjects. Smoking
      significantly reduced the histamine plasma levels in cancer patients (p=0.0044).
      Such a decrease was not significant in the controls (p=0.063). A significant
      decrease in selenium plasma levels in the cancer patients (p=0.005) was also
      observed. The data suggest that histamine and selenium are two factors involved
      in the pathogenesis of lung cancer, which could be used in protective and
      therapeutic strategies.

PMID- 16886618
TI  - The RNA interference of amino acid transporter LAT1 inhibits the growth of KB
      human oral cancer cells.
AB  - BACKGROUND: Amino acid transporters are essential for growth and proliferation in
      all living cells. Among the amino acid transporters, the system L amino acid
      transporters are the major nutrient transport system responsible for the Na+
      independent transport of neutral amino acids, including several essential amino
      acids. The L-type amino acid transporter 1 (LAT1) is overexpressed to support
      cell growth in malignant tumors. Double-stranded RNA-mediated RNA interference
      (RNAi) analysis can be used in a wide variety of eukaryotes to induce the
      sequence-specific inhibition of gene expression. The current study attempted to
      investigate the effects of silencing LAT1 expression with small interfering RNA
      (siRNA) on cell growth in the KB human oral squamous cell carcinoma. MATERIALS
      AND METHODS: The effects of silencing LAT1 expression with siRNA KB on cell
      growth were examined using RT-PCR, Western blot analysis, amino acid transport
      measurement and the MTT assay. RESULTS: In the RT-PCR and Western blot analyses,
      the siRNA of LAT1 inhibited the expressions of LAT1 mRNA and protein. The uptake
      of [14C]L-leucine was also inhibited by the siRNA of LAT1. In the MTT assay, the
      siRNA of LAT1 inhibited the growth of the KB cells in a time-dependent manner,
      indicating that this growth inhibition was induced by the LAT1-mediated blocking
      of neutral amino acid transport. CONCLUSION: The transport of neutral amino
      acids, including several essential amino acids, into the KB human oral squamous
      cell carcinoma is mainly mediated by LAT1. Furthermore, LAT1 could be a new
      target for the inhibition of cancer cell growth.

PMID- 16886619
TI  - Expression of dihydrodiol dehydrogenase and resistance to chemotherapy and
      radiotherapy in adenocarcinoma cells of lung.
AB  - BACKGROUND: The cytoplasmic enzyme dihydrodiol dehydrogenase (DDH) plays an
      important role in the detoxification process. Recently, the overexpression of DDH
      was detected in non-small cell lung cancer (NSCLC) cells and patients with DDH
      overexpression were shown to have a significantly higher incidence of early tumor
      recurrence and distant metastasis. In this study, the correlation between DDH
      expression and resistance to cisplatin, adriamycin and radiotherapy in NSCLC was
      examined. MATERIALS AND METHODS: Seven lung adenocarcinoma cell lines (H23, H838,
      H1437, H1648, H2009, H2087 and H2126) were used in the study. The DDH level was
      determined by reverse transcription polymerase chain reaction and immunoblotting.
      Drug- and radiation-mediated cytotoxicity was measured by clonogenic assay. DDH
      isoforms (DDH1, DDH2 and DDH3) were transfected into H23 cells that did not
      express DDH to examine their effects on drug and radiation resistance. RESULTS:
      DDH-overexpressed adenocarcinoma cells exhibited a much higher resistance to
      doxorubicin, cisplatin and irradiation than cells with lower DDH expression. The
      DDH2- and DDH1-transfectants showed higher drug and radiation resistance than the
      DDH3-trasnfectant. CONCLUSION: Resistance to both anticancer drugs and
      irradiation in lung adenocarcinoma cells was closely associated with DDH
      activity. DDH1 and DDH2 were the main isoforms responsible for these effects.

PMID- 16886620
TI  - The co-expression of c-myc and p53 increases and reaches a plateau early in oral
      oncogenesis.
AB  - BACKGROUND: The balance between cell proliferation and apoptosis plays a
      significant role in cancer development. The expressions of the p53 and c-myc
      genes, both strongly related to cell proliferation and apoptosis, were studied in
      sequential histological grades of oral carcinogenesis in an animal model.
      MATERIALS AND METHODS: Thirty-seven hamsters were divided into three groups
      (A,B,C), which were treated with 9,10-dimethyl-1,2-benzanthracene and sacrificed
      at 10,14 or 19 weeks, respectively, after treatment. The histological status of
      the oral lesions in the experimental groups corresponded well with tumour
      advancement (from dysplasia to moderately-differentiated carcinoma). Tumour
      sections were studied immunohistochemically. RESULTS: The expressions of both p53
      and c-myc increased significantly in precancer stages and then reached a plateau.
      The same pattern was observed in the animal groups with the culmination of
      expression of both genes in group A. CONCLUSION: The coexpression of p53 and c
      myc proteins in the earlier stages of oral oncogenesis may be used for the early
      detection of premalignant lesions.

PMID- 16886621
TI  - Monoclonal antibody to human esophageal cancer endothelium inhibits angiogenesis
      and tumor growth.
AB  - BACKGROUND: Monoclonal antibodies to tumor endothelial cells (TECs) hold great
      promise for cancer angiogenesis-targeted therapy. The aim of the present study
      was to develop such an agent for esophageal cancer treatment. MATERIALS AND
      METHODS: BALB/c mice were immunized with human esophageal tumor endothelial cells
      (ETECs) cultured with tumor homogenate. MAbs were produced, screened by
      immunofluorescence and immunohistochemistry (IHC) and an IgG1K mAb 4B3 was
      selected. The mAb 4B3 antigen was analyzed by IHC and Western blotting. The
      antibody's effects on ETECs were determined by adhesion and tube formation
      assays, while its therapeutic potential was evaluated with a tumor model
      established by co-inoculating mice with the human esophageal cancer cell lines
      KYSE180 and ETECs. RESULTS: MAb 4B3 recognized a 40-kDa surface antigen
      preferentially expressed on TECs and other stromal cells in human malignant
      tissues of esophagus, stomach, colon, liver, lung and breast compared with their
      normal counterparts. The antigen was not detected on cancer cells or normal
      epithelia in these tissues, nor was it detectable on any cells in the mouse
      xenografts of KYSE180, including the host endothelia. MAb 4B3 inhibited ETEC
      adhesion to extracellular matrix proteins and tube formation in vitro. The
      antibody inhibited angiogenesis and growth of the tumor formed by coinoculation.
      CONCLUSION: These results suggest that mAb 4B3 has therapeutic potential for
      esophageal cancer.

PMID- 16886622
TI  - Comparative promoter analysis of doxorubicin resistance-associated genes suggests
      E47 as a key regulatory element.
AB  - Working under the assumption that up- or downregulation of genes implicated in
      chemoresistance may be the result of altered function of regulatory transcription
      factors (TF), over-represented TF-binding sites of gene lists previously
      associated with doxorubicin resistance were the target of our search. First, a
      data warehouse was set up containing 52 genes which were present in at least two
      gene lists; of those, proximal promoter sequences (1 kb upstream and 0.05 kb
      downstream of the transcriptional start sites) could be retrieved from genomic
      databases for 45 genes using the EZ-Retrieve. The TOUCAN tool MotifScanner, which
      searches the TRANSFAC database, was used to detect TF-binding sites (TFBSs) in
      our set of sequences. The statistics tool of the Java program TOUCAN was applied
      to the data with the appropriate expected frequencies file to compare the
      measured prevalence to a background model. The most significantly over
      represented TFBS was that of E47 (p=0.00024, prevalence: 0.2 vs. background:
      8.19E-6). In summary, based on the results of our analysis it is hypothesized
      that the E47 transcription factor may contribute to doxorubicin resistance.

PMID- 16886623
TI  - Inhibition of caveolin-1 expression by incadronate in PC-3 prostate cells.
AB  - BACKGROUND: Caveolin-1 is an essential component of caveolae and its expression
      is known to be increased in human prostate cancer. The reduction of caveolin-1
      expression has been reported to decrease the tumorigenic and metastatic potential
      of prostate cancer. MATERIALS AND METHODS: Caveolin-1 expression was determined
      by real-time RT-PCR and Western blot analysis. RESULTS: Incadronate, a third
      generation bisphosphonate, was found to inhibit the caveolin-1 mRNA and protein
      expression in PC-3 prostate cells. The decrease in caveolin-1 mRNA expression by
      incadronate was prevented by co-incubation with geranylgeranyol, but not with
      farnesol. Moreover, treatment of GGTI-286, a geranylgeranyl transferase
      inhibitor, but not FTI-277, a farnesyl transferase inhibitor, also resulted in
      the inhibition of caveolin-1 mRNA expression. CONCLUSION: These results indicate
      that the decrease in caveolin-1 expression elicited by incadronate is related to
      the inhibition of protein geranylgeranylation.

PMID- 16886624
TI  - Tissue microarray analysis of FAS, Bcl-2, Bcl-x, ER, PgR, Hsp60, p53 and Her2-neu
      in breast carcinoma.
AB  - BACKGROUND: The aim of this study was to detect immunohistochemical markers in
      breast carcinoma by means of tissue microarray analysis (TMA) and to associate
      their expressions with clinicopathological features and prognosis. Fatty acid
      synthase, bcl-2, bcl-x, p53, estrogen and progesterone receptors, heat shock
      protein 60 and Her2-neu (c-erbB-2) were evaluated in a group of 149 breast
      carcinoma patients with a 5-year follow-up period. MATERIALS AND METHODS: TMA
      blocks were made by using duplicate 0.6-mm diameter tissue cores from each
      paraffin block. RESULTS: Statistical analysis revealed that tumor stage (p=0.003)
      and node status (p=0.001) were the only two prognostic markers of disease-free
      survival. Moreover, FAS and bcl-x showed an independent effect on recurrence
      (p=0.005). The node status was the only marker of overall survival (p=0.05).
      CONCLUSION: Our data confirmed recent reports associating the stage of disease,
      FAS and Bcl-x expressions with recurrence and outcome. These data demonstrated
      that TMA is an effective substitute for conventional histochemical
      immunohistochemical techniques.

PMID- 16886625
TI  - The expression of hypoxia-inducible factor-1alpha (HIF-1alpha) and angiogenesis
      markers in hyperplastic and malignant prostate tissue.
AB  - BACKGROUND: The process of ingrowth of new blood vessels is stimulated by the
      action of vascular endothelial growth factor (VEGF), while it may be
      simultaneously related to the degree of tissue hypoxia. Hypoxia-inducible factor
      1alpha (HIF-1alpha) is a protein of cellular response to hypoxia. The
      relationship between hypoxia and angiogenesis in patients with benign prostate
      hyperplasia (BPH) and prostate cancer (PCa) was examined. MATERIALS AND METHODS:
      One hundred and seventy (170) prostatic tissue samples were immunohistochemically
      evaluated. The microvessel density (MVD) was calculated by CD34 immunostaining;
      the angiogenetic profile was further assessed using a monoclonal antibody against
      VEGF. HIF-1alpha immunoreaction was recognized through nuclear staining of
      positive cells. RESULTS: CD34, VEGF and HIF-1alpha staining reactions were
      significantly higher in the PCa group than in the BPH group. In both groups, an
      interrelationship between the immunoexpression of CD34 and HIF-1alpha, VEGF and
      HIF-1alpha, as well as VEGF and CD34 was detected. CONCLUSION: MVD, VEGF
      cytoplasmic immunoreactivity and HIF-1alpha immunoreaction were more prominent in
      PCa than in BPH and were also significantly associated with high-grade
      carcinomas.

PMID- 16886626
TI  - DNA content analysis, expression of Ki-67 and p53 in rat urothelial lesions
      induced by N-butyl-N-(4-hydroxybutyl) nitrosamine and treated with mitomycin C
      and bacillus Calmette-Guerin.
AB  - N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN)-induced urothelial carcinogenesis is
      a useful model for studying urothelial carcinogenesis. Here, the DNA content and
      the expression of Ki-67 and p53 in urothelial lesions induced by BBN and treated
      with mitomycin C (MMC) and Bacillus Calmette-Guerin (BCG) were investigated.
      Female Fisher 344 rats were distributed into five groups treated with 0.05% BBN
      in their drinking water for 20 weeks. Ten animals were used as negative control.
      Intravesical instillations were performed with MMC, BCG and physiological saline
      solution (PSS), once per week, for 6 weeks. The animals were sacrificed 1 week
      after the last intravesical instillation. DNA ploidy analysis was carried out by
      static cytometry. Ki-67 and p53 were analysed immunohistochemically in paraffin
      embedded tissue. The incidence of lesions developed in rats with PSS was greater
      than in rats instilled with MMC and BCG. The incidence of aneuploidy was lower in
      tumours treated with MMC and BCG. Low- and high-grade papillary carcinoma treated
      with MMC and BCG showed a decrease in labelling index and an increase of
      apoptotic index. The proliferative index was correlated with the apoptotic index
      (r=0.438, p<0.01). Significant correlations were also found between the
      proliferative index and lesion, and the apoptotic index and lesion (r=0.425,
      p<0.01 and r=0.275, p<0.01), respectively. A significant correlation was found
      between ploidy and the apoptotic index (r=0.245, p<0.05). Our results provide
      information on the biological behaviour of chemically-induced bladder tumours
      treated with MMC and BCG.

PMID- 16886627
TI  - Radiation-induced effect of adenine (vitamin B4) on mitomycin C activity. In
      vitro experiments.
AB  - The radiation-induced biological behavior of adenine (vitamin B4) was
      investigated in vitro under various conditions, implementing breast cancer cells
      (MCF-7 line) as a model. In aerated media (46% OH and 54% O2*-) at pH=7.4,
      adenine at low concentration (2 micromol) acted as an efficient radiation
      protecting agent. At higher concentration, however, it inhibited cytostatic
      properties with regard to cancer cells. This double-track activity is based on
      its chemical structure. Similar features of adenine were also observed in air
      free (46% OH, 44% e- aq, 10% H) as well as in media saturated with N2O (90% OH,
      10% H), but with different efficiencies. In the presence of mitomycin C (MMC),
      adenine retained its double-track behavior. Hence, adenine and MMC compete for
      the e- aq, but the electronically excited adenine molecules can transfer
      electrons to MMC, leading to the additional formation of active MMC-. By
      implementation of formate for the conversion of OH and H into the transient *COO
      , which subsequently transfers electron to MMC, a highest efficiency of MMC- was
      obtained.

PMID- 16886628
TI  - A comparison of the tumor growth inhibitory effect of intermittent and continuous
      administration of the somatostatin structural derivative TT-232 in various human
      tumor models.
AB  - The tumor growth inhibitory efficacy of the somatostatin structural derivative TT
      232 was studied using different routes of administration and treatment schedules
      in various human tumor models. TT-232, containing a five-residue ring structure,
      has a strong antitumor activity both in vitro and in vivo. The antineoplastic
      activity of TT-232 has been found to be associated with the induction of
      programmed cell death in tumor cells, resulting in highly-selective elimination
      of the neoplastic tissue. The study compared the antitumor efficacy of TT-232 in
      various long-term administration routes; the intermittent (injection) versus
      continuous (infusion) treatment via subcutaneously-inserted Alzet osmotic
      minipumps in different human tumor models: T-47/D human breast carcinoma and A
      431 human epidermoid carcinoma. Treatment with TT-232 started after disease
      development. The antitumor activity of TT-232 was evaluated on the basis of the
      tumor growth inhibition. In the case of T-47/D human breast carcinoma, the
      intermittent treatment resulted in 23%-26% and the infusion treatment resulted in
      48%-53% tumor growth inhibition. The tumor growth inhibitory effect of TT-232 on
      A-431 human epidermoid carcinoma tumor resulted in 35%-43% (intermittent
      treatment) and 70%-74% (continuous treatment) decreases in tumor volume. This
      antitumor efficacy of TT-232 was observed in the two human tumors investigated.
      In this study, the route of infusion was shown to increase drug efficacy relative
      to conventional delivery methods. The results suggest that TT-232 is an effective
      and promising antitumor agent.

PMID- 16886629
TI  - Gemcitabine treatment of experimental C6 glioma: the effects on cell cycle and
      apoptotic rate.
AB  - Gemcitabine (dFdCyd) is a deoxycytidine analogue showing a broad spectrum of
      cytotoxic activity; additionally, at non-cytotoxic concentrations, it is a potent
      radiosensitiser. Its in vitro and in vivo effects were studied on C6 rat glioma.
      In vitro, dFdCyd induced an increase in S-phase cells at the end of treatment,
      with a reduction in G1 and G2 cell cycle-phase cells and relevant effects on the
      apoptotic rate. The in vivo effects of dFdCyd were studied on rats bearing
      intracranial C6 glioma. The drug was administered at a dose of 120 mg/Kg every 3
      days x 4 doses. A significant effect on tumour growth was detected by
      longitudinal MRI analyses. Furthermore, the drug induced an inhibitory effect on
      tumour growth, 72 h after a 300 mg/Kg single dose. Analyses performed on tumour
      specimens showed relevant G1-phase accumulation and about 45% apoptotic cells.
      The present results justify further studies to determine the potential efficacy
      of dFdCyd in the treatment of malignant gliomas.

PMID- 16886630
TI  - Ad-fRNK and Ad-p53 cooperate to augment drug-induced death of a transformed cell
      line.
AB  - BACKGROUND: Transformed cells have abnormalities in the survival pathways
      contributing to drug resistance. These abnormalities include p53 mutations and
      increased focal adhesion kinase (FAK) expression. Because FAK regulates cell
      survival via p53-dependent and -independent pathways, it was hypothesized that
      combined therapy using wild-type p53 and an inhibitor of FAK (FRNK) would
      sensitize cells to anticancer drugs. MATERIALS AND METHODS: RPMI 2650 cells were
      infected with recombinant adenoviruses causing overexpression of p53 (Ad-p53) and
      FRNK (Ad-FRNK). Cell viability and apoptosis were measured using in vitro assays,
      whereas protein expression was determined by Western blotting. RESULTS: Co
      infection of cells with Ad-p53 and Ad-FRNK induced more cellular apoptosis than
      transfection with either agent alone. Likewise, the co-transfection of cells with
      Ad-FRNK and Ad-p53 improved the cytotoxic response to four commonly used
      anticancer drugs relative to cells transfected with Ad-FRNK alone, Ad-p53 alone,
      or the equivalent amount of control adenovirus. This effect was associated with
      loss of endogenous FAK protein.

PMID- 16886631
TI  - Antiangiogenic effect of sulindac sulfide could be secondary to induction of
      apoptosis and cell cycle arrest.
AB  - BACKGROUND: The development of colon cancer is probably angiogenesis-dependent.
      Recently, sulindac sulfide was shown to possess anti-angiogenic activity. In the
      present work, the question of whether this activity reflects a specific
      interaction with angiogenesis or is secondary to the effect of sulindac sulfide
      on the survival of endothelial cells was addressed. MATERIALS AND METHODS:
      Endothelial and normal mouse fibroblast cell lines were incubated with non
      steroidal anti-inflammatory drugs (NSAIDs), arachidonic acid (AA) and
      prostaglandin E2 (PGE2). Cell viability (survival), PGE2 synthesis, cell cycle
      and apoptosis were measured. Western blotting and semi-quantitative RT-PCR
      multiplex methods verified the changes in the levels of pro-apoptotic proteins
      and their expressions, respectively. RESULTS: Sulindac sulfide and celecoxib
      inhibited the survival of endothelial cells, whereas other NSAIDs were
      ineffective. In contrast to celecoxib, sulindac sulfide did not affect the
      survival of normal fibroblast cells. Both agents inhibited the production of PGE2
      from AA and arrested the cell cycle in the S-phase. Moreover, sulindac sulfide
      activated caspases 3 and 8, decreased the levels of Bax and Bid proteins, caused
      cleavage of PARP and increased the expressions of the bax and caspase 3 genes.
      CONCLUSION: The results suggest that the anti-angiogenic activity of sulindac
      sulfide is secondary to the inhibition of endothelial cell survival resulting
      from cell cycle arrest and apoptosis.

PMID- 16886633
TI  - Antiproliferative effects of mistletoe (Viscum album L.) extract in urinary
      bladder carcinoma cell lines.
AB  - BACKGROUND: The aim of the study was to evaluate the antiproliferative potency of
      Viscum album extract (VA-E) in human bladder carcinoma cell lines with regard to
      its possible use for intravesical therapy of superficial bladder cancer.
      MATERIALS AND METHODS: Proliferation (MTT-test or 3H-thymidine incorporation),
      necrotic disintegration (3H-thymidine release of prelabelled cells) and portions
      of apoptotic and/or necrotic cells (Annexin-V binding, propidium iodide (PI)
      labelling and DNA-fluorescence profiles by flow cytometry) were measured in four
      different human bladder carcinoma cell lines (T24, TCCSUP, J82 and UM-UC3)
      cultured in vitro. RESULTS: Antiproliferative effects of VA-E were observed in
      the four bladder carcinoma cell lines tested. Metabolic activity could also be
      completely abrogated by short-time contact of the cells with VA-E. Apoptosis and
      necrosis, as underlying mechanisms of action, were differentially expressed by
      the different cell lines. CONCLUSION: VA-E and cytotoxic proteins, i.e.,
      mistletoe lectins (ML) and viscotoxins (VT), were able to block the growth of
      bladder carcinoma cells. Together with the immunomodulating properties of VA-E,
      the observed antiproliferative potency might give a rationale for the topical
      intravesical application of VA-E for the treatment of superficial bladder cancer.

PMID- 16886632
TI  - Antioxidants modify the effect of X rays on blood vessels.
AB  - BACKGROUND: It was recently shown, with the chicken embryo chorioallantoic
      membrane (CAM) model, that X rays decrease the number of blood vessels within the
      first hours after irradiation. In the present study, the possible role of
      reactive oxygen species (ROS) and nitric oxide (NO) in this effect of X rays was
      evaluated. MATERIALS AND METHODS: An area of 1 cm2 of the CAM, restricted by a
      plastic ring, was irradiated at room temperature, in the presence or absence of
      the tested agents. The number of vessels was measured 48 h after irradiation of
      the tissue. RESULTS: Superoxide dismutase and tempol, which are superoxide ion
      scavengers and catalase, a hydrogen peroxide scavenger, had additive effects,
      while dimethylsulfoxide, a hydroxyl radical scavenger, reversed the vascular
      targeting effect of X rays. The combination of X rays with W1400, a selective
      inducible NO synthase (NOS) inhibitor, had an additive effect on the decrease in
      number of CAM blood vessels. In contrast, L-NAME, a non-selective NOS inhibitor
      and D-NAME, its inactive analog, reversed the vascular-targeting effect of X
      rays, possibly due to their ability to act as potent hydroxyl radical scavengers.
      CONCLUSION: The above data collectively suggest that hydroxyl radicals mediate
      the damaging effects of X rays on CAM blood vessels, while antioxidants against
      other ROS do not protect against the vascular-targeting effect of X rays.

PMID- 16886634
TI  - An in vivo analysis of the herbal compound essiac.
AB  - BACKGROUND: Essiac is a herbal compound that has been in common use with cancer
      patients in North America for over 80 years. Despite its relatively widespread
      use, there are no peer-reviewed published reports of in vivo studies regarding
      the use of this compound. MATERIALS AND METHODS: Essiac was administered orally
      to test animals prior to all experiments. Standard assays to test protection from
      ethanol-induced gastric ulceration and carbon tetrachloride-induced hepatic
      injury were performed on Wistar rats. Assays of postglucose-load serum glucose
      and cellular and humoral immune modulation were conducted on ICR and BALB/C mice,
      respectively. RESULTS: Essiac demonstrated a modest gastric protective effect via
      reduction of ethanol-induced gastric ulceration. However, Essiac did not
      demonstrate significant hepatoprotective, hypoglycemic or immunomodulatory
      properties. CONCLUSION: Essiac, administered in established in vivo experimental
      models, did not significantly demonstrate its purported physiological modifying
      effects.

PMID- 16886635
TI  - Primitive and bone metastatic renal carcinoma cells promote osteoclastogenesis
      through endothelial cells.
AB  - BACKGROUND: The contribution of angiogenesis to renal carcinoma bone metastases
      is virtually unknown. MATERIALS AND METHODS: The effect of a cell line from a
      renal carcinoma bone metastasis (CRBM) was compared in vitro with the primitive
      renal adenocarcinoma line ACHN, by evaluating the influence on the ability of
      bone endothelial cells to activate osteoclasts. RESULTS: The ACHN-conditioned
      medium produced a significant expression of macrophage-colony-stimulating factor
      mRNA. The conditioned medium from ACHN, CRBM, or from endothelial cells
      previously stimulated with the neoplastic cell-conditioned media, had no direct
      effect on osteoclast differentiation from blood precursors (PBMC), such as CRBM
      and ACHN co-cultured with PBMC. However, PBMC co-cultured with endothelial cells
      previously stimulated with the CRBM-conditioned medium showed significantly
      higher levels of tartrate-resistant acid phosphatase. CONCLUSION: It is possible
      that the bone metastatic line CRBM releases factors that induce endothelial cells
      to favor osteoclast differentiation.

PMID- 16886636
TI  - Anticancer versus antigrowth activities of three analogs of the growth-inhibitory
      peptide: relevance to physicochemical properties.
AB  - A 34-amino acid peptide has been synthesized based on an amino acid sequence from
      the third domain of native full-length alpha-fetoprotein, which has been shown to
      have both antigrowth and anticancer activities. This peptide, known as the growth
      inhibitory peptide (GIP), has two cysteine residues and demonstrates reduced
      antigrowth activity after long-term storage, presumably due to disulfide bond
      formation. The disulfide bridge problem was addressed by replacing the two
      naturally occurring cysteines with either glycines, alanines, or serines (to
      produce the G-, A- and S-peptides, respectively). The non-hydrophobic G- and S
      peptides were found to exist as dimers, while the more hydrophobic C- and A
      peptides formed trimers in solution under certain conditions of pH and peptide
      concentration. The A-peptide was already known to display anticancer activity;
      however, the G- and S-serine analogs have not been studied in depth since they
      had demonstrated low antigrowth activities in rodent uterine assays. Using both
      in vivo and in vitro assays, the A-, G- and S-peptides were shown to exhibit
      various degrees of cancer growth suppression. An in vitro culture assay, using
      MCF-7 breast cancer cells, demonstrated that both the G- and S-peptides showed
      modest cancer growth suppression, while the A- analog showed strong inhibition at
      doses ranging from 10(-5) M to 10(-7) M. In contrast, an in vivo ascites tumor
      study of all four peptides showed them to have notable activity in the
      suppression of mouse mammary tumor growth. Overall, our data indicated that
      physicochemical properties, such as hydrophobicity, oligomeric state and
      secondary structure, contribute to the anticancer activity of both the active C-
      peptide and its analogs. In addition, the antigrowth rodent uterine assay was not
      always predictive of the anticancer potential of the peptide forms, suggesting a
      difference between the mechanism of peptide action in the antigrowth models and
      that in the anticancer assay. Notably, the antigrowth assay failed to predict the
      marked anticancer activity of the analogs against a mammary tumor, indicating
      that the growth bioassay cannot always be relied upon as a screening protocol.

PMID- 16886637
TI  - The estrogen receptor alpha C975G variant in familial and sporadic breast cancer:
      a case-control study.
AB  - BACKGROUND: The estrogen receptor alpha (ESR1) mediates the effect of estrogen in
      target tissues. Estrogen is important in breast cancer development and several
      polymorphic variants in the ESR1 gene have been investigated for association with
      breast cancer. The C975G variant is the most extensively studied and has been
      suggested to be a risk factor. MATERIALS AND METHODS: The frequency of the C975G
      variant was investigated in 288 sporadic, 197 low-risk non-BRCA1/2 familial and
      191 high-risk non-BRCA1/2 familial breast cancer cases and 653 controls. RESULTS:
      There was a lower frequency of the C975G variant in high-risk familial breast
      cancer cases compared to the controls (18% versus 22%, p=0.046). The odds ratio
      (OR) for the GG homozygotes was 0.2 (95% CI: 0.06-0.8) compared to the CC
      homozygotes. No association was seen with sporadic or low-risk familial breast
      cancer. CONCLUSION: The results of this study indicated that the common C975G
      variant may have an effect on familial breast cancer susceptibility.

PMID- 16886639
TI  - Indication and efficacy of adjuvant chemotherapy with oral fluoropyrimidines for
      dukes' B colorectal cancer.
AB  - BACKGROUND: Identifing patients prone to colorectal cancer recurrence is of
      importance in providing appropriate adjuvant chemotherapy. In this retrospective
      study on Dukes' B colorectal cancer, patients at high risk of recurrence were
      identified by clinicopathological factors, and the efficacy of adjuvant
      chemotherapy with oral fluoropyrimidines was evaluated. PATIENTS AND METHODS: The
      subjects were 229 patients with Dukes' B colorectal cancer who had undergone
      curative surgical resection. The relationship between each factor and cancer
      related survival was examined. RESULTS: In all the patients, the 5-year
      cumulative survival rate was 83.5% and the recurrence rate was 20.1%. The
      multivariate analyses indicated that the depth of invasion was the most
      significant prognostic factor. The cases with tumor exposed at the serosa or
      which invaded other organs were considered as a high-risk group. The 5-year
      survival rate in high-risk patients with adjuvant chemotherapy was significantly
      better than those without chemotherapy (75.8% and 44.0%, respectively, p=0.0008).
      The patients who received chemotherapy tended to show a decrease in the
      recurrence rate, especially in the liver and lung (p=0.0346). CONCLUSION: In
      Dukes' B colorectal cancer, the cases with invasion depth se or si were
      considered to be at high risk of recurrence or death. Adjuvant chemotherapy was
      effective for such high-risk patients, especially decreasing recurrence in the
      liver and lung.

PMID- 16886638
TI  - Phase I/II study of paclitaxel + carboplatin for refractory or recurrent non
      small cell lung cancer.
AB  - A gene-drug correlation analysis was previously performed in lung cancer cell
      lines using the NC160 program. On the basis of this work, a phase I/II pilot
      study of weekly paclitaxel and carboplatin (CBDCA) was subsequently planned for
      refractory or recurrent non-small cell lung cancer (NSCLC). Safety and antitumor
      effects were evaluable in all 30 patients registered for this study. Seven
      patients were stage IIIB and 23 were stage IV. At level 5 (paclitaxel 100 mg/m2
      and CBDCA AUCS), toxicities were not dose-limiting factors, but three out of the
      initial six cases had infusion skips. Our recommended dose was paclitaxel 100
      mg/m2 and CBDCA AUC5. The response rate was 50% (9/18)(95% CI: 27-73%) in step 5.
      The median survival time was 12 months. This combination showed a promising
      clinical activity with mild toxicity and should be selected for the
      investigational arm of phase III trials to be compared with either docetaxel or
      pemetrexed.

PMID- 16886640
TI  - Detection of oncogenic HPV and identification of 72Arg polymorphic p53 by in situ
      PCR for clinical routine purposes.
AB  - BACKGROUND: Ano-genital carcinoma is a polyfactorial and polygenic disease.
      Certain strains of human papillomavirus (HPV) have been detected in a high
      percentage of patients. It has been suggested that p53 polymorphisms may be
      relevant for the interaction with viral proteins that inactivates p53. MATERIALS
      AND METHODS: Patients were selected on the basis of HPV infection, clinical
      history, positive PAP test and type of lesion. In situ PCR was performed on smear
      samples, in four steps: a) preparation on clean biobond-treated slides, b)
      permeabilisation and digestion; c) in situ PCR amplification; d) in situ
      hybridisation with a fluorescent probe. RESULTS: In situ PCR analysis of the
      smears confirmed the results obtained by classic PCR and by in situ PCR of frozen
      sections. CONCLUSION: In situ PCR on smears could be used in targeted-screening
      for young and post-menopausal women, as well as in the development of large scale
      studies to establish the connection among the presence of HPV, p53 polymorphisms
      and the risk of cervical cancer. ABBREVIATIONS: PCR, polymerase chain reaction;
      OsO4, osmium tetroxide; HPV, human papilloma virus; PBS, phosphate-buffered
      saline; SDS, sodium dodecyl sulphate.

PMID- 16886641
TI  - Immunohistochemical expression of 14-3-3 sigma protein in intraductal papillary
      mucinous tumor and invasive ductal carcinoma of the pancreas.
AB  - BACKGROUND: 14-3-3 sigma (sigma) has been shown to be overexpressed in pancreatic
      cancers by a c-DNA microarray technique. However, the expression of 14-3-3 sigma
      in intraductal papillary-mucinous tumor (IPMT) of the pancreas remains unclear.
      MATERIALS AND METHODS: To evaluate the biological importance of 14-3-3 sigma
      expression in pancreatic carcinogenesis, immunohistochemistry for 14-3-3 sigma,
      CDX2, MUC1, MUC2, p53, p16 and Ki-67 was carried out on 33 IPMTs and the results
      were compared with those for 14 invasive ductal carcinomas (IDCs). RESULTS: The
      frequency of 14-3-3 sigma immunoreactivity was 70% and 100% in IPMT and IDC,
      respectively. The frequency of MUCI and Ki-67 immunoreactivity was significantly
      higher in IDC than IPMT. In IPMT, dark columnar cell types prevailed over clear
      columnar cell types in terms of the frequency of the Ki-67 labeling index.
      CONCLUSION: The overexpression of 14-3-3 sigma was confirmed in both IDC and
      IPMT. Therefore, this overexpression might occur in the early stages of
      pancreatic carcinogenesis. Moreover, IPMT composed of dark columnar cells might
      be a potentially more advanced form than that made up of clear columnar cells.

PMID- 16886643
TI  - Primary osteoblastic osteosarcoma in an elderly female: a case report of
      perplexing presentation.
AB  - With advances in imaging technology and increased alertness by clinicians, the
      reported incidence of primary vertebral osteosarcoma (PVOS) has increased in
      recent times and, therefore, the importance of its correct diagnosis has
      repeatedly been emphasized. One such case of PVOS is reported, that presented
      with insidious clinical, radiological and pathological findings, resulting in a
      slightly delayed final diagnosis and treatment.

PMID- 16886642
TI  - Bisphosphonates and oral cavity avascular bone necrosis: a review of twelve
      cases.
AB  - BACKGROUND: Intravenous bisphosphonates are the current standard of care for the
      treatment of hypercalcemia of malignancy and for the prevention of skeletal
      complications associated with bone metastases. Recently, retrospective case
      studies have reported an association between long-term bisphosphonate therapy and
      osteonecrosis of the jaws. PATIENTS AND METHODS: The data for twelve patients,
      referred to either an oral and maxillofacial surgeon or to an oral medicine
      specialist for the management of clinically apparent chronic oral osteonecrosis
      of unknown etiology, were reviewed. All had received cancer-related therapy
      simultaneously with bisphosphonate management. RESULTS: The typical presenting
      symptoms were pain and exposed bone at the site of a previous tooth extraction.
      In most patients, the lesions initially occurred after dental extraction or other
      odontostomatological procedures, while five had a spontaneous event. Biopsy of
      the involved area showed the presence of necrotic lacunae, with infiltration of
      lymphocytes and histiocytes. In nine cases, there was histological or cytological
      diagnosis of suspicious osteomyelitis. No correlation was observed between the
      intraoral lesions and myelosuppression secondary to antineoplastic therapy.
      CONCLUSION: Based on the patients' respective histories, clinical presentations
      and responses to surgical and antibiotic treatments, it appears that the
      pathogenesis of this osteonecrotic process is most consistent with localized
      vascular insufficiency. In our opinion, the mechanism by which bisphosphonates
      compromise bone vascularity may be related to their effect on the osteoclasts.
      The potent bisphosphonate-mediated inhibition of osteoclast function serves to
      decrease bone resorption and inhibit normal bone turnover remodeling, resulting
      in microdamage accumulation and a reduction in some mechanical properties of the
      bone.

PMID- 16886644
TI  - Percutaneous localization of pulmonary nodules prior to thoracoscopic surgery by
      CT-guided hook-wire.
AB  - BACKGROUND: When performing thoracoscopic surgery in patients with small
      pulmonary nodules, intraoperative localization can be difficult and time
      consuming. The percutaneous localization of suspicious intrapulmonary lesions was
      evaluated pre-operatively to facilitate the resection of the lesion and to avoid
      thoracotomy. MATERIALS AND METHODS: Thoracoscopies were performed in 13 patients
      with intrapulmonary nodules previously localized by CT-scan and flagged
      percutaneously with a hook-wire. Immediately after the procedure, the patient was
      transferred to the operating room and thoracoscopic pulmonary wedge resection was
      performed. RESULTS: All the nodules were properly identified. The time to
      position the wire was 20-30 min and thoracotomy could be avoided in all patients.
      The nodules were 0.5 cm - 6 cm in size and situated 1 cm - 4 cm subpleurally.
      CONCLUSION: Guide-wire identification of an intrapulmonary nodule is a safe,
      elegant, time-saving and reliable method. The lack of manual examination of
      pulmonary parenchyma in thoracoscopy is compensated for by precise pre-operative
      localization.

PMID- 16886645
TI  - Serum TRACP 5b and ICTP as markers of bone metastases in breast cancer.
AB  - BACKGROUND: The purpose of this cross-sectional study was to evaluate the value
      of serum tartrate-resistant acid phosphatase 5b (TRACP 5b) and carboxyterminal
      telopeptide of type I collagen (ICTP) separately and in combination as markers of
      bone metastases compared to total alkaline phosphatase (tALP) in breast cancer.
      MATERIALS AND METHODS: Two groups of patients were studied, one with verfied bone
      metastases (N=46) and one without bone metastases (N=141). Bone marker levels
      were correlated with the presence or absence of bone metastases. RESULTS: Serum
      TRACP 5b concentrations exhibited the largest area under the receiver-operating
      characteristics (ROC) curve (AUC=0.845), followed by ICTP (0.818) and tALP
      (0.814) when all patients were included in the analysis. With the combination of
      TRACP 5b and ICTP, the AUC increased to 0.881. In multivariate regression
      analysis, all three markers were significant predictors of bone metastases.
      CONCLUSION: Serum TRACP 5b, ICTP and tALP exhibited equal performances in the
      detection of bone metastases. The combination of TRACP with ICTP did not
      significantly improve the detection of bone metastases over tALP.

PMID- 16886646
TI  - Rapid infusion of ibandronate in lung cancer patients with bone metastases.
AB  - BACKGROUND: The high prevalence of bone metastases in stage IV non-small cell
      lung cancer (NSCLC) patients contributes substantially to the burden of the
      disease by resulting in significant skeletal morbidity. Ibandronate is a new
      generation of bisphosphonates (BPs) with demonstrated clinical benefit in breast
      and prostate cancer patients with bone metastases. PATIENTS AND METHODS: In 32
      patients with newly diagnosed NSCLC and bone metastases, 4 mg of ibandronate were
      administered, as a rapid 20-minute intravenous infusion every 3-4 weeks. RESULTS:
      A total of 189 infusions were administered over a 24-month period, during which a
      statistically significant decrease in calcium serum levels (p=0.03) was observed.
      The serum levels of alkaline phosphatase (ALP) were also decreased, but not
      significantly. With regard to clinical efficacy, 24 of our patients stabilized or
      reduced their need for analgesic treatment. The reduced time of infusion (20 min
      vs. 2 h) did not correlate with any side-effects, including vital sign
      deterioration and renal dysfunction. CONCLUSION: The rapid infusion of
      ibandronate in lung cancer patients with bone metastases is a safe and convenient
      procedure that may be administered in a day-clinic setting.

PMID- 16886647
TI  - A phase II study of gemcitabine plus cisplatin in previously untreated advanced
      ovarian cancer.
AB  - BACKGROUND: The primary objective was the evaluation of the effects of
      gemcitabine plus cisplatin on the overall response rate (ORR) of patients with
      advanced ovarian cancer; the secondary assessments included toxicity, time to
      progressive disease (TtPD) and the duration of response. MATERIALS AND METHODS:
      Chemonaive patients with stage III/IV ovarian cancer received gemcitabine 1250
      mg/m2 (d 1,8) and cisplatin 75 mg/m2 (d 1), every 21 days for a maximum of six
      cycles. RESULTS: Between March 1999 and June 2003, 28 patients (median age 52
      years, range 23-72) had received chemotherapy. Of 26 assessable patients, the ORR
      was 57.7% (95% CI, 42.7%-83.6%) based on four complete responses and eleven
      partial responses, six patients experienced stable disease, while five had
      progressive disease. The median survival was 28.1 months (95% CI, 11.4-33.4
      months), the median TtPD was 10.5 months (95% CI, 1.4-44.2 months) and the median
      duration of response was 24.3 months (95% CI, 12.3-33.4 months). The most common
      grade 3/4 toxicities were nausea/vomiting (15.2%) and neutropenia (10.7%). There
      was no grade 3 or 4 thrombocytopenia. CONCLUSION: Gemcitabine plus cisplatin
      exhibited activity in advanced ovarian cancer with an acceptable toxicity
      profile.

PMID- 16886649
TI  - Role of surgery in treatment of locally advanced prostate cancer.
AB  - The proportion of prostate cancer diagnosed at localized stages increased from
      56.7% to 74. 0% between 1973 and 1993 ("stage migration"). A corresponding
      increase in the number of radical prostatectomies performed each year was also
      noted. Nomograms are mathematical algorithms derived from statistical models that
      are used to predict outcomes for an individual patient, or for groups of
      patients. In fact, careful pre-operative patient and tumor selection before
      radical prostatectomy is mandatory. Locally advanced prostate cancer is defined
      as tumor that has extended clinically beyond the prostatic capsule, with invasion
      of the pericapsular tissue, apex, bladder neck or seminal vescicle, but without
      lymph node involvement or distant metastasis. It is estimated that 12-15% of
      prostate cancer are stage T3. Overstaging or understaging of this cancer is
      common. Correct staging of clinical T3 disease is even more difficult and both
      overstaging pT2 and understaging pT4 or pN+ are common. The goals of treatment
      for T3 tumors are to cure the disease, prolong survival or metastasis-free
      survival and improve the quality of life. The authors reviewed the most important
      studies, investigated radical prostatectomy as monotherapy for locally advanced
      prostate cancer and the integration of surgery with hormonal treatment. The EAU
      guidelines on prostate cancer state that radical prostatectomy in locally
      advanced disease is an option for selected patients with small T3, PSA <20 ng/ml,
      Gleason score <8 and a life expectancy > 10 years. Ten to 15% of clinical T3 are
      overstaged as pT2. This may lead to the possibility of curing these patients with
      surgery as the monotherapy. The increased use of nomograms and increased
      knowledge of recognized prognostic factors could lead to the selection of a large
      number of patients, often with a long life expectancy, who could benefit from
      surgical treatment.

PMID- 16886648
TI  - Vinorelbine and 5-fluorouracil bolus and/or continuous venous infusion plus
      levofolinic acid as second-line chemotherapy for metastatic breast cancer: an
      analysis of results in clinical practice of the Gruppo Oncologico Italia
      Meridionale (GOIM).
AB  - BACKGROUND: This retrospective study evaluated the activity and toxicity profile
      of a regimen of vinorelbine and 5-fluorouracil with levofolinic acid, given to a
      large series of patients with recurrent or refractory metastatic breast cancer
      after first-line chemotherapy. PATIENTS AND METHODS: Overall, 286 evaluable
      patients were included in the analysis. Two chemotherapy schedules were reviewed:
      a) the bolus regimen consisted of levofolinic acid 100 mg/m2 and 5-fluorouracil
      375 mg/m2, both administered i.v. on days 1,2 and 3, plus vinorelbine 25 mg/m2
      i.v. bolus on days 1 and 8 every 3 weeks; b) the infusional regimen of
      levofolinic acid 100 mg/m2 given as a 2-hour infusion, followed by 5-fluorouracil
      400 mg/m2 i.v. bolus and by 5-fluorouracil 600 mg/m2 administered as 22-hour
      continuous venous infusion (c.v.i) for 2 days, plus vinorelbine i.v. bolus on
      days 1 and 8. RESULTS: Overall, twelve patients achieved a complete response (4%;
      95%CL 2%-7%) and 115 patients showed a partial response (40%, 95%CL 34%-46%), for
      an overall response rate of 44% (95CL 39%-50%). Sixty-one patients had stable
      disease (21%) and 98 patients progressive disease (34%). The tumor growth control
      rate was 63% (95%CL 60%-71%). Patients with soft tissue metastases as the
      dominant disease showed the highest response rate (56%), followed by viscera
      (48%) and bone (33%). The difference in response rate between patients with
      dominant visceral disease versus those with dominant bone disease was
      statistically significant (p=0.038). Patients treated with the bolus schedule
      achieved a 40% overall response rate with a 5% complete response rate, while
      those who received the infusional regimen had a 48% overall response rate with a
      5% complete response rate. This difference was not statistically significant
      (p=0.164). The overall median duration of objective responses was 8.3 months
      (range 4-14 months), median time to progression of the all series was 6.1 months
      (range 2-24 months) and the median overall survival was 14.6 months (range 3-32).
      There was a statistically significant difference in survival among responder and
      non-responder patients (p=0.0009). CONCLUSION: The results of this large off
      trial analysis confirmed the clinical activity and adverse-event profile reported
      in controlled clinical trials of the vinorelbine/ 5-fluorouracil with levofolinic
      acid regimen in clinical practice. This combination regimen was active with a low
      toxicity burden and, therefore, represents a good therapeutic choice for patients
      who require second-line chemotherapy.

PMID- 16886651
TI  - Follow-up of high-grade squamous intra-epithelial lesions (H-SIls) in human
      immunodeficiency virus (HIV)-positive and human papillomavirus (HPV)-positive
      women. analysis of risk factors.
AB  - BACKGROUND: Human immunodeficiency virus (HIV)-positive women are at high risk of
      co-infection from human papillomavirus (HPV) and of developing squamous
      intraepithelial lesions of the cervix. MATERIALS AND METHODS: From April 1997 to
      March 1999, 86 women, affected by high-grade squamous intra-epithelial lesions (H
      SILs), were enrolled: 41 were HIV+ (CD4+ count >500/ml) and 45 were HIV-. The
      diagnosis of high-grade squamous intra-epithelial lesion (H-SIL) was established
      for each patient by Pap test, colposcopy and guided biopsy. For all samples, the
      HPV/DNA test was also performed by PCR. The patients' lesions and recurrence were
      treated by cone biopsy or large loop excision (LEEP). Annual controls were
      performed for 5 years. RESULTS: A high rate of alcohol and drug use (60.7% vs.
      31.4%; p=0.004; 80% vs. 27.5%; p<0.001, respectively) and number of male partners
      (4.5 vs. 3.0; p<0.001) were found in the HIV+ patients, compared to the HIV-
      patients. Both groups were HPV+ for high-risk types. No difference was found in
      the percentage of patients who had received a second LEEP. CONCLUSION: Our
      findings suggest the treatment of H-SIL in HIV-positive women, for a longer
      disease-free survival, or a lower risk of developing cervical cancer.

PMID- 16886650
TI  - Serum testosterone: A potentially adjunct screening test for the assessment of
      the risk of prostate cancer among men with modestly elevated PSA values (> or
      =3.0 and <10.0 ng/ml).
AB  - Whether serum testosterone (T) can become an adjunct test able to validate the
      PSA-weighted risk of prostate cancer (PR.CA) in the "grey" diagnostic area (PSA
      =3.0 to <10.0 ng/ml) was investigated. Seven hundred and eighteen men
      participated in a prostate screening program using the cutoff PSA value of > or
      =3.0 ng/ml. PR.CA was found in 26% (22/85) of men with PSA testing within the
      "grey" diagnostic area and 58% (7/12) with PSA testing > or =10 ng/ml, among the
      97 men who agreed to undergo transrectal ultrasound-guided biopsy (TRUS-guided
      biopsy). The PSA values showed a statistically significant positive association
      with diagnosis of PR.CA, whereas T and the T/PSA ratio were inversely and
      significantly related to the disease. In addition, out of 718 subjects, 45 (2.6%)
      were found to have a T value <2.6 ng/ml and another 78 (10.8%) had "low normal T
      value" (2.6> or = T <3.0 ng/ml). Of the hypogonadal men, 16 received testosterone
      enanthate (depot T; 250 mg/ml oily injection, intramuscularly: i.m.; TRT) and
      three had PSA levels >3.0 ng/mlpost-TRT; one was eventually diagnosed with PR.CA.
      An empirically-determined cut-off of the T/PSA ratio [>95 ("negative") or <0.95
      ("positive")] was found to be optimal with regard to both
      sensitivity/specificity. This test was "positive" among 95.5% of the PR.CA
      patients, whereas 81% of biopsies confirmed that non-PR.CA had a "negative" TIPSA
      ratio, indicating that this ratio can become an adjunct screening test in
      assessing the risk of PR. CA; in particular, the odds of PR. CA increasing
      sharply (1/0.08= 12.5 times) with a decrease of the TIPSA ratio by one standard
      deviation. We conclude that the measurement of the serum T value can become an
      adjunct test validating further the PSA-weighted risk of PR. CA within the "grey"
      diagnostic area.

PMID- 16886652
TI  - Prevalence of acetowhite areas in male partners of women affected by HPV and
      squamous intra-epithelial lesions (SIL) and their prognostic significance. A
      multicenter study.
AB  - BACKGROUND: Estimates for the prevalence of cervical HPV infection vary and are
      only available for a few populations with regard to male partners. Attention has
      been drawn to the male role in cancer progression from cervical intra-epithelial
      neoplasia, but most of the male lesions are subclinical and only visible after
      acetowhite staining. The prognostic significance of acetowhite areas, of male
      partners of women affected by HPV and preneoplastic lesions, was evaluated.
      MATERIALS AND METHODS: A cohort of 3210 male partners of women affected by HPV
      infection and/or preneoplastic lesion of the lower genital tract was observed
      from 1987 to 2001. Acetowhite changes were assessed 5 min after the application
      of 5% solution of acetic acid and biopsies were tested for HPV-DNA by PCR.
      Patients with HPV lesions underwent CO2 laser surgery and follow-up. RESULTS: Of
      the 3210 male partners, 39.12% exhibited clinical HPV lesions and 3.64%
      subclinical lesions identified as acetowhite areas. In the group of 117 male
      partners with acetowhite areas, the HPV-DNA test was positive (HPV 6-11) in
      36.75% and negative in 63.24% (p<0.001). No statistical differences were observed
      between HPV+/- groups regarding their sexual habits. The HPV-positive infection
      group compared to the HPV-negative group showed a statistically significant
      difference for CO2 laser surgery (p<0.001). CONCLUSION: The acetic acid test can
      give false-positives and is not a specific indicator of HPV infection, and thus
      the limited efficacy of tests for acetowhite areas was confirmed. The treatment
      of clinical lesions is necessary. Follow-up represents the major route to the
      diagnosis of preneoplastic lesions in men and for the prevention of cervical
      carcinoma in their female partners.

PMID- 16886653
TI  - Non-small cell lung cancer in the young: a retrospective analysis of diagnosis,
      management and outcome data.
AB  - BACKGROUND: Non-small cell lung cancer (NSCLC) in young patients is uncommon and
      is thought to constitute a distinct oncological entity with characteristic
      clinicopathological patterns. Since the reported data are scant and discordant,
      the presentation, management and outcome data of NSCLC patients aged under 45
      years of age were analyzed and compared with those of patients over 45 years old.
      Prognostic factors for risk classification were also evaluated. MATERIALS AND
      METHODS: The data were abstracted from the Hellenic Cooperative Oncology Group
      (HeCOG) cancer registry database. The presentation, management and outcome data
      of patients with histologically confirmed NSCLC, managed from 1989 until 2004 in
      HeCOG participating centers, were retrospectively analyzed. The
      clinicopathological characteristics of patients aged < and > than 45 years old
      were compared and evaluated for prognostic significance regarding outcome.
      RESULTS: The data for NSCLC patients (1906), of whom 115 were aged <45, were
      retrieved. In comparative analysis, the young patients were more frequently
      asymptomatic at diagnosis, while older patients presented significantly higher
      rates of thoracic pain, cough and fatigue (p<0.01). The young patients were more
      commonly diagnosed with adenocarcinoma and less frequently with squamous cancer
      than patients aged over 45. Although the stage distribution was distinct, with
      older patients presenting higher rates of stage IV disease (21.9% vs. 12.2%), the
      rates of early lung cancer (stages I-IIIa) were similar. The overall survival
      (OS) was not significantly different (median OS 12 vs. 11.5 months, p=0.277).
      Among patients who underwent first-line palliative chemotherapy, young
      individuals had a significantly shorter time to progression: 4.3 vs. 5.8 months
      (p=0.0049). Univariate and multivariate regression analyses established the
      prognostic usefulness of the performance status, disease stage and disease-free
      interval for the risk of death, both in the total number of patients (1906) and
      in young patients (115). CONCLUSION: This large retrospective series failed to
      present strong evidence that NSCLC among young individuals constitutes a distinct
      clinicopathological entity with differing biological behavior, since the same
      clinicopathological prognostic factors were valid in both age groups. Molecular
      phenotypic studies are needed to shed light on this controversial subject.

PMID- 16886654
TI  - Multiorgan resections for advanced colorectal cancer.
AB  - BACKGROUND: A retrospective review is presented of a single institution's
      experience with multivisceral resections for locally-advanced colorectal cancer.
      MATERIALS AND METHODS: Twenty-eight patients, who had undergone RO multiorgan
      resection, were identified from the database of a total of 1150 patients operated
      on for colorectal carcinoma in the years 1995-2005 at a single center. There were
      twelve total pelvic exenterations and 16 patients had undergone en bloc primary
      tumor resection with adherent organs, such as the spleen, diaphragm, pancreas,
      stomach, kidney, etc. The patients were followed-up according to a standard
      protocol. RESULTS: The post-operative mortality was 7%, the average follow-up
      21.6 months and the 5-year survival 45%. CONCLUSION: Our results confirmed that,
      in the case of invasion of colorectal cancer to the adjacent intra-abdominal
      organs or structures, multiorgan resection 'offers the only chance of potentially
      curative treatment.

PMID- 16886655
TI  - Serum interleukin-6 levels in patients with gastric MALT lymphoma compared to
      gastric and pancreatic cancer.
AB  - BACKGROUND: Interleukin-6 (IL-6) plays a major role in inflammatory processes and
      various malignancies. Serum IL-6 levels from patients with gastric MALT lymphoma,
      gastric cancer and pancreatic cancer was investigated. PATIENTS AND METHODS: The
      serum 11-6 levels were obtained in a total of 86 patients. A two-tailed Mann
      Whitney-test was performed to compare the results. A p-level <0.05 was deemed
      statistically significant. RESULTS: In lymphoma patients, the mean IL-6 levels
      were 12.633 pg/ml (SD 10.465). The levels for gastric cancer were 6.324 pg/ml (SD
      11.497) and 27.4 pg/ml (SD 86.272) for pancreatic cancer. A comparison between
      MALT lymphoma and gastric cancer revealed a significant difference (p=0.0030),
      while no difference was found between MALT lymphoma and pancreatic cancer. The 11
      6 levels, however, were higher in pancreatic cancer than gastric cancer (p
      =0.0040). CONCLUSION: Our results might reflect a greater importance of IL-6 in
      the development and growth of MALT lymphoma and, possibly, pancreatic cancer than
      in gastric cancer.

PMID- 16886656
TI  - Complete response of urothelial carcinoma to chemotherapy in renal allograft
      recipients: a two-case study.
AB  - BACKGROUND: The risk of urothelial carcinoma (UC) is increased in patients with
      end-stage renal disease. Standard regimens for UC (e.g., M-VAC) carry substantial
      toxicity, which could be exacerbated in patients with end-stage renal disease
      receiving kidney transplantation, because of the need to take immunosuppressants
      for life. PATIENTS AND METHODS: Patients who had metastatic UC, and normal bone
      marrow, liver and kidney functions, were eligible. The TP-HDFL regimen included:
      paclitaxel 70 mg/m2 1-hour intravenously (i.v.) on days 1, 8; cisplatin 35 mg/m2
      24-hour (i.v.) on days 2 and 9; and 5-fluorouracil 2, 000 mg/m2 and leucovorin
      300 mg/m2 24-hour (i.v.) on days 2 and 9; repeated every 21 days. Concomitant
      immunosuppressants were maintained during chemotherapy. RESULTS: From 2003 to
      2004, two female renal allograft recipients developed renal pelvis UC with para
      aortic and lung metastasis, respectively. They received four to six cycles of the
      TP-HDFL regimen and achieved complete response. There was neither significant
      toxicity, nor immunosuppressant dose-adjustment. The patients remained disease
      free for 2 and 1 year, respectively, after completion of the chemotherapy.
      CONCLUSION: The TP-HDFL regimen showed activity and can be safely used in renal
      allograft recipients with metastatic UC.

PMID- 16886657
TI  - Human papillomaviruses (HPV) in tissue specimens of oral squamous cell papillomas
      and normal oral mucosa.
AB  - BACKGROUND: The etiology of oral squamous cell papillomas (OSCP) is still
      unresolved. MATERIALS AND METHODS: The presence of human papillomavirus (HPV) was
      examined, using PCR and three different consensus primers, in tissue specimens
      obtained from 49 patients with OSCP and 49 tissue specimens of histologically
      normal oral mucosa obtained from the same number of individuals, who matched the
      patients with OSCP in age, gender and localization of the obtained tissue
      specimens. RESULTS: Amplifiable DNA was recovered from 44 out of 49 and 45 out of
      49 tissue specimens of OSCP and normal oral mucosa, respectively. HPV-6 was
      detected in three and HPV-16 in one out of 44 OSCP specimens tested. Three tissue
      specimens of normal oral mucosa were HPV DNA-positive, harboring HPV-6, HPV-11
      and HPV-31. CONCLUSION: Since no significant difference in the prevalence of HPV
      DNA between the patients with OSCP and the control subjects (9.1% vs. 6.7%;
      p=0.694) was observed, HPV is deemed to play a limited role in the etiology of
      OSCP, at least in Europe.

PMID- 16886658
TI  - Vitamin D analogs in cancer prevention and therapy.
AB  - The Second International Symposium on "Vitamin D Analogs in Cancer Prevention and
      Therapy", was held in Lubeck, Germany, May 7-8, 2005. This meeting was
      specifically designed to summarize the latest developments in the epidemiology,
      molecular biology, metabolism, biological effects and clinical use of vitamin D
      analogs, leading to new concepts for their application in cancer prevention and
      therapy. Forty keynote lectures were presented at the Symposium and the following
      conclusions were summarized at a round-table discussion. Cancer Prevention:
      Evidence from epidemiological and laboratory investigations now convincingly
      demonstrate that vitamin D deficiency and insufficiency are underrecognized
      worldwide problems that are associated with several health problems, including
      the higher prevalence and unfavorable course of cancer. There is an urgent need
      for additional well-designed studies to define the optimal vitamin D status (25
      hydroxyvitamin D serum level) and for campaigns to better inform the public and
      medical profession alike about the health risks related to vitamin D deficiency
      and insufficiency. Cancer Therapy: Knowledge of the underlying molecular
      mechanisms that mediate the antitumor effects of vitamin D analogs has expanded
      greatly during recent years and results from the first clinical trials indicate
      that such analogs hold promise for cancer therapy, most probably in combination
      with other agents. However, the era of vitamin D analogs in cancer therapy has
      just begun and efforts to perform well-designed clinical studies and to develop
      new analogs with fewer systemic side-effects have to continue.

PMID- 16886659
TI  - Vitamin D and cancer.
AB  - The correlation between decreased morbidity and mortality of cancer and exposure
      to sunlight is known. The many biological functions of vitamin D that contribute
      to cancer prevention have only recently begun to be appreciated. Once activated
      1,25-dihydroxyvitamin D [1,25(OH)2D3] functions as a potent inhibitor of normal
      and cancer cellular proliferation. Vitamin D deficiency in mice led to a 60%
      increase in colon tumor growth, compared to vitamin D-sufficient mice. The ligand
      binding domain of the Vitamin D receptor was shown to accommodate a class of
      1,25(OH)2D3-analogs that possess an additional side-arm. These novel Gemini
      analogs were evaluated in vitro and in vivo. Select Gemini analogs were 100 times
      or more effective in inhibiting colon tumor growth in mice, compared to their
      parent compound. Correcting vitamin D deficiency may decrease the risk of
      developing colon cancer, while the novel Gemini 1,25(OH)2D3-analogs have the
      potential for therapeutic application in human colon cancer.

PMID- 16886661
TI  - Vitamin D compounds: activity against microbes and cancer.
AB  - Vitamin D3 is produced in skin and is sequentially metabolized by the liver and
      kidney to the biologically active form 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. It
      is a seco-steroid hormone that regulates calcium homeostasis within the body. The
      genomic actions of 1,25(OH)2D3 are modulated through the vitamin D receptor
      (VDR). VDR belongs to a superfamily of nuclear receptors that transduce hormonal
      signals from the immediate environment and transactivate genes in response to
      these signals. Target genes contain hormone response elements (VDREs) in their
      promoters to which heterodimers of VDR and retinoid X receptors (RXR) can bind
      and transactivate expression of the target genes. The VDR is expressed in at
      least 30 different target tissues including bone, kidney, blood, breast,
      prostate, gut, activated B- and T- lymphocytes, monocytes and keratinocytes).
      Most dividing cell types, normal and malignant, can express VDR and respond to
      1,25(OH)2D3. Although 1,25(OH)2D3 and its analogs (termed deltanoids) are
      important regulators of calcium and bone metabolism, their non-calciotropic
      activities that include inhibition of cell proliferation, promotion of cell
      differentiation and modulation of immune cell function have spurred interest in
      therapeutic applications in a wide variety of diseases. In this report, the
      anticancer and newly discovered antimicrobial actions of 1,25(OH)2D3 and
      deltanoids are reviewed.

PMID- 16886660
TI  - Mechanisms of vitamin D-mediated growth inhibition in prostate cancer cells:
      inhibition of the prostaglandin pathway.
AB  - Calcitriol (1,25-dihydroxyvitamin D3), the active form of vitamin D, promotes
      growth inhibition and differentiation in prostate cancer (PCa) cells. To unravel
      the molecular pathways of calcitriol actions, cDNA microarray analysis was used
      to identify novel calcitriol target genes including two that play key roles in
      the metabolism of prostaglandins (PGs), known stimulators of PCa growth and
      progression. Calcitriol significantly decreases the expression of the PG
      synthesizing cyclooxygenase-2 (COX-2) gene, while increasing that of PG
      inactivating 15-prostaglandin dehydrogenase (15-PGDH). Calcitriol also inhibits
      the expression of the PG receptors EP2 and FP. It reduces the levels of
      biologically active PGs and inhibits PG actions in PCa cells, thereby decreasing
      the proliferative stimulus of PGs. We postulate that the regulation of the PG
      pathway contributes to the growth inhibitory actions of calcitriol. We also
      propose that calcitriol can be combined with non-steroidal anti-inflammatory
      drugs (NSAIDs) that inhibit COX enzyme activity, as a potential therapeutic
      strategy in PCa.

PMID- 16886662
TI  - The antitumor efficacy of calcitriol: preclinical studies.
AB  - Studies in our laboratory demonstrate that vitamin D (1,25
      dihydroxycholecalciferol or calcitriol) has significant antitumor activity in
      vitro and in vivo in murine and human squamous cell, prostate, lung, pancreatic
      and myeloma model systems. Calcitriol induces G0/G1 arrest, modulates p27 and
      p21, the cyclin-dependent kinase (cdk) inhibitors implicated in G1 arrest, and
      induces cleavage of caspase 3, PARP and the mitogen-activated protein kinase
      (MEK) in a caspase-dependent manner. Calcitriol also decreases phospho-Erk (P
      Erk) and phospho-Akt (P-Akt), kinases that regulate cell survival pathways and up
      regulate the pro-apoptotic signaling molecule, MEKK-1. Glucocorticoids enhance
      calcitriol-mediated activities pre-clinically in vitro and in vivo. Dexamethasone
      (dex) significantly potentiated the antitumor effect of calcitriol and decreased
      calcitriol-induced hypercalcemia. Both in vitro and in vivo, dex increased
      vitamin D receptor (VDR) ligand binding in the tumor while decreasing binding in
      intestinal mucosa, the site of calcium absorption. These studies demonstrated
      that calcitriol has significant antiproliferative activity in a number of pre
      clinical model systems and form the groundwork for on-going clinical studies
      investigating calcitriol as an anticancer agent.

PMID- 16886663
TI  - Vitamin D compounds: clinical development as cancer therapy and prevention
      agents.
AB  - While 1,25 dihydroxycholecalciferol (calcitriol) is best recognized for its
      effects on bone and mineral metabolism, epidemiological data indicate that low
      vitamin D levels may play a role in the genesis and progression of breast, lung,
      colorectal and prostate cancer, as well as malignant lymphoma and melanoma.
      Calcitriol has strong antiproliferative effects in prostate, breast, colorectal,
      head/neck and lung cancer, as well as lymphoma, leukemia and myeloma model
      systems. Antiproliferative effects are seen in vitro and in vivo. The mechanisms
      of these effects are associated with G0/G1 arrest, induction of apoptosis,
      differentiation and modulation of growth factor-mediated signaling in tumor
      cells. In addition to the direct effects on tumor cells, recent data strongly
      support the hypothesis that the stromal effects of vitamin D analogs (e.g.,
      direct effects on tumor vasculature) are also important in the antiproliferative
      effects. Antitumor effects are seen in a wide variety of tumor types and there
      are few data to suggest that vitamin D-based approaches are more effective in any
      one tumor type. Glucocorticoids potentiate the antitumor effect of calcitriol and
      decrease calcitriol-induced hypercalcemia. In addition, calcitriol potentiates
      the antitumor effects of many cytotoxic agents. Preclinical data indicate that
      maximal antitumor effects are seen with pharmacological doses of calcitriol and
      that such exposure can be safely achieved in animals using a high dose,
      intermittent schedule of administration. AUC and C(max) calcitriol concentrations
      of 32 ng.h/ml and 9.2 ng/ml are associated with striking antitumor effects in a
      murine squamous cell carcinoma model and there is increasing evidence from
      clinical trials that such exposures can be safely attained in patients. Another
      approach to maximizing intra-tumoral exposure to vitamin D analogs is to inhibit
      their catabolism. The data clearly indicate that agents which inhibit the major
      vitamin D catabolizing enzyme, CYP24 (24 hydroxylase), potentiate calcitriol
      killing of prostate tumor cells in vitro and in vivo. Phase I and II trials of
      calcitriol, either alone or in combination with carboplatin, taxanes or
      dexamethasone, as well as the non-specific CYP24 inhibitor, ketoconazole, have
      been initiated in patients with androgen-dependent and -independent prostate
      cancer and other advanced cancers. The data indicate that high-dose calcitriol is
      feasible on an intermittent schedule, no dose-limiting toxicity has been
      encountered, but the optimal dose and schedule remain to be delineated. Clinical
      responses have been seen with the combination of high-dose calcitriol +
      dexamethasone in androgen-independent prostate cancer (AIPC) and, in a large
      randomized trial in men with AIPC, potentiation of the antitumor effects of
      docetaxel were seen.

PMID- 16886664
TI  - Epigenetic corruption of VDR signalling in malignancy.
AB  - BACKGROUND: The ligand-mediated switch from binding co-repressor to co-activator
      complexes is central to the transcriptional actions of the vitamin D receptor
      (VDR) and other nuclear receptors. The capacity of deregulated co-repressors to
      attenuate the responsiveness of VDR signalling in cancer models was examined.
      MATERIALS AND METHODS: Proliferation and gene regulation studies were undertaken
      in non-malignant and malignant cell line and primary models. RESULTS: Both
      primary tissue models and cancer cell lines displayed a spectrum of suppressed
      responsiveness towards 1alpha, 25 hydroxy vitamin D3 (1alpha25(OH)2D3) which
      correlated with elevated co-repressor content: specifically, elevated silencing
      mediator of retinoid and thyroid hormone receptors/nuclear co-repressor 2
      (NCoR2/SMRT) in prostate cancer cell lines and primary tumour cultures, and
      elevated nuclear receptor co-repressor 1 (NCoR1) in breast cancer cell lines.
      Interestingly, whilst the cancer cell lines frequently also displayed reduced VDR
      content, the primary tumour material retained and/or elevated VDR mRNA,
      correlated with co-repressor content. Functional approaches towards NCoR2/SMRT
      (siRNA) in prostate cancer cells or NCoR1 (overexpression) in non-malignant
      breast epithelial cells confirmed a role in suppressing VDR transcriptional and
      cellular actions. Targeted co-treatments of 1alpha25(OH)2D3 plus HDAC inhibitors
      (TSA, NaB) resulted in re-expression of antiproliferative target genes (e.g.,
      GADD45alpha, p21(waf1/cip1)) and synergistic inhibition of proliferation.
      CONCLUSION: These data suggest that VDR actions in solid tumours are retained,
      but were skewed by epigenetic mechanisms to suppress selectively
      antiproliferative target gene promoter responses. This molecular lesion provides
      a novel chemotherapy target for acceptable doses of 1alpha25(OH)2D3 plus HDAC
      inhibitors.

PMID- 16886666
TI  - Vitamin D status and breast cancer risk.
AB  - BACKGROUND: Local synthesis of 1alpha,25(OH)D3 in breast tissue may contribute to
      maintenance of normal cell function and could be impaired with low circulating
      levels of the precursor 25hydroxyvitamin D. The aims of this study were to: i)
      assess the association between breast cancer risk and plasma 25OHD3 concentration
      and ii) define the significance of expression of the 25OHD activating enzyme
      CYP27b1 in non-malignant and malignant models of breast epithelial cells.
      MATERIALS AND METHODS: Breast cancer patients and control women were recruited
      and their 25OHD levels measured by enzyme-linked immunosorbent assay (ELISA).
      MRNA expression of CYP271b and the 1,25(OH)2D3 inactivating enzyme CYP24 were
      measured in breast cancer cell lines by RT-PCR and correlated with immunoblotting
      approaches to the translated proteins. RESULTS: For women with 25OHD < 50 nM the
      odds ratio for breast cancer compared with women with 25OHD > 50 nM was 3.54 (CI
      1.89-6.61, p < 0.001). CYP271b and CYP24 were detected in non-malignant and
      malignant cell models. Protein levels of 24OHase but not 1alphaOHase were
      decreased at confluence in the cell lines. CONCLUSION: Impaired local generation
      of 1,25OHD3 may contribute to the development of breast cancer.

PMID- 16886665
TI  - Vitamin D metabolism in human prostate cells: implications for prostate cancer
      chemoprevention by vitamin D.
AB  - BACKGROUND: Prostate cells can produce 1alpha,25-dihydroxyvitamin D3
      (1alpha,25(OH)2D3) from 25-hydroxyvitamin D3 (25(OH)D3) to regulate their own
      growth. Here, the questions of whether prostate cells express vitamin D-25
      hydroxylase (25-OHase) and can convert vitamin D3 to 1alpha,25(OH)2D3 were
      investigated. MATERIALS AND METHODS: Protein and receptor binding assays were
      used to determine 25(OH)D3 and 1alpha,25(OH)2D3, respectively. Measurements of
      proliferation by 3H-thymidine incorporation, and 1alpha,25(OH)2D-responsive gene
      expression by real-time qPCR and by Western blot were used as functional assays
      for the presence of 25-OHase activity. RESULTS: Prostate cells metabolized
      vitamin D3 to 1alpha,25(OH)2D3. Vitamin D3 up-regulated 25(OH)D-24R-hydroxylase
      and IGFBP3, two 1alpha,25(OH)2D-responsive genes, in prostate cells. CYP2R1 was
      the major form of 25-OHase expressed in normal and cancerous prostate cells as
      determined by qPCR. CONCLUSION: The autocrine synthesis of 1alpha,25(OH)2D3 from
      vitamin D3 suggests that maintaining adequate levels of serum vitamin D could be
      a safe and effective chemo-preventive measure to decrease the risk of prostate
      cancer.

PMID- 16886667
TI  - Dysfunction of the vitamin D endocrine system as common cause for multiple
      malignant and other chronic diseases.
AB  - Extensive research on the CYP27B1-encoded 25-(OH)D-1alpha-hydroxylase has
      contributed much to our understanding about how locally produced 1,25-(OH)2D3
      exerts tissue-specific control of cellular growth, differentiation and function.
      Because many types of epithelial, mesenchymal and immune cells express the 25
      (OH)D-1alpha-hydroxylase, many organ functions are necessarily affected by
      changes in the activity of the enzyme. It is hypothesized that this is likely to
      occur under conditions of hypovitaminosis D, i.e., at serum 25-(OH)D levels below
      30 nM, because extra-renal 25-(OH) D-1alpha-hydroxylase activity is critically
      limited by the availability of its substrate. This can provide an explanation, on
      a molecular and cellular basis, for the many observations that significant
      associations exist between a compromised vitamin D status and the pathogenesis of
      frequent chronic diseases. In addition to skeletal disorders, vitamin D
      insufficiency is a risk factor for malignancies, particularly of the colon,
      breast and prostate gland, as well as for chronic inflammatory and autoimmune
      diseases (insulin-dependent diabetes mellitus, inflammatory bowel disease,
      multiple sclerosis, etc.).

PMID- 16886668
TI  - Hepatic activation and inactivation of clinically-relevant vitamin D analogs and
      prodrugs.
AB  - Like most pharmaceutical agents, vitamin D analogs are subject to hepatic
      metabolism by a variety of cytochrome P450 (CYP)-based systems. Metabolism can
      involve activation as well as inactivation of the vitamin D analog and one of the
      more successful families includes the 1alpha-hydroxyvitamin D prodrugs (1alpha-OH
      D2, 1alpha-OH-D3, 1alpha-OH-D4, 1alpha-OH-D5), that all require a step of
      activation. Some of these prodrugs are in use or clinical trial because they have
      a therapeutic advantage over calcitriol. However, the nature of the activation of
      these molecules is poorly understood, particularly with regard to the CYP isoform
      involved. Various transfected CYPs and hepatic cell lines combined with tandem LC
      MS analysis were used to investigate the metabolism of a spectrum of vitamin D
      analogs, including 1alpha-OH-Ds and the topical analog, calcipotriol. In the case
      of the 1alpha-OH-Ds, evidence was found of multiple sites of side-chain
      hydroxylation consistent with the generation of more than one active form. The
      potential involvement of CYP27A and other putative 25-hydroxylases in 1alpha-OH-D
      activation was also shown, as well as the potential for CYP24 activation and
      inactivation. In the case of calcipotriol, the respective roles of non-vitamin D
      related CYPs and CYP24 in the catabolism of this anti-psoriatic drug were
      dissected out using cell lines with or without CYP24 expression, allowing us to
      demonstrate the potential contribution of CYP24 to "vitamin D resistance". The
      implications of hepatic metabolism in the context of other facets thought to play
      a role in the mechanism of action of anticancer and antiproliferative vitamin D
      analogs are discussed.

PMID- 16886669
TI  - Genistein and 17beta-estradiol, but not equol, regulate vitamin D synthesis in
      human colon and breast cancer cells.
AB  - Extrarenal synthesis of the active vitamin D metabolite 1,25-dihydroxyvitamin-D3
      (1,25-D) has been observed in cells derived from human organs prone to sporadic
      cancer incidence. Enhancement of the synthesizing hydroxylase CYP27B1 and
      reduction of the catabolic CYP24 could support local accumulation of the
      antimitotic steroid, thus preventing formation of tumors of e.g., colon and
      breast. By applying quantitative RT-PCR and HPLC it was observed that in colon
      (Caco-2) and breast-(MCF-7) derived cells, 17beta-estradiol and genistein induced
      CYP27B1 but reduced CYP24 activity, while equol was inactive. Mammary cells
      express both estrogen receptors (ER) a and beta, while colon cells express mainly
      ERbeta, possibly explaining why MCF-7 cells were more affected. These results
      indicate a potential, new approach for cancer prevention by counteraction of the
      1,25-D-driven negative feedback, i.e., down-regulation of CYP27B1 and up
      regulation of CYP24, which prevents its own local accumulation. However, mammary
      cells may be more susceptible to this than colonocytes.

PMID- 16886670
TI  - The likely role of vitamin D from solar ultraviolet-B irradiance in increasing
      cancer survival.
AB  - BACKGROUND: Solar ultraviolet-B (UVB) and vitamin D have been found inversely
      correlated with cancer incidence, mortality, and survival rates in many studies.
      MATERIALS AND METHODS: In this work, two sets of cancer data were used: age
      adjusted cancer incidence and mortality rates in 2002 for 21 Western developed
      countries and cancer survival data from Eurocare-3 for nine European countries
      for cancer diagnosed from 1990 to 1994. The data were used in ecologic studies
      with respect to latitude, an index of solar UVB irradiance, and dietary supply
      factors for 1985. RESULTS: Statistically significant correlations of effective or
      actual survival rates with increasing latitude were found for breast, colon,
      gastric, lung, ovarian, pancreatic, prostate and renal cancer, and non-Hodgkin's
      lymphoma. Five-year survival rates south of 50 degrees N were 20%-50% higher than
      those near 55 degrees N. CONCLUSION: These results provide additional support for
      an increase in cancer survival rates linked with natural vitamin D.

PMID- 16886671
TI  - Analysis of 25-hydroxyvitamin D3-1alpha-hydroxylase in normal and malignant
      breast tissue.
AB  - BACKGROUND: The presence of extra-renal 25-hydroxyvitamin D3 [25(OH)D3]-1alpha
      hydroxylase (1alpha-OHase) has been reported in several cell types including
      prostate and colon cancer cells. Additionally, alterations in the local
      production of 1alpha,25-dihydroxyvitamin D [1alpha,25(OH)2D3] have been
      implicated in the tumorigenesis of these malignancies. The aim of this study was
      to analyze whether normal breast tissue or breast cancer cells expressed 1alpha
      OHase and to evaluate whether breast tissue possessed the capacity to produce
      1alpha,25(OH)2D3 from 25(OH)D3. MATERIALS AND METHODS: Total RNA was extracted
      from normal breast tissue (n = 11), breast carcinomas (n = 12) and cultured MCF-7
      breast cancer cells for real-time (LightCycler using specific hybridization
      probes) and conventional PCR analysis. RESULTS: mRNA for 1alpha-OHase was
      detected in breast cancer tissue and in MCF-7 breast cancer cells. Interestingly,
      the mRNA levels for 1alpha-OHase were significantly increased in breast cancer
      compared to normal breast tissue. When the MCF-7 cells were treated with
      1alpha,25(OH)2D3, cell proliferation was inhibited in a dose-dependent manner.
      Incubation of the MCF-7 cells with [3H]-25(OH)D3 resulted in its conversion to
      [3H]-1,25(OH)2D3. The 1alpha-OHase activity in the MCF-7 cells was blocked by a
      specific cytochrome P450 inhibitor, clotrimazole. CONCLUSION: The data suggest
      that at least breast cancer cells expressed 1alpha-OHase mRNA and, therefore,
      might have the ability to synthesize 1alpha,25(OH)2D3 within the cells. The local
      production of 1alpha,25(OH)2D3 might play an important role in regulating the
      proliferation and differentiation of breast cells. We hypothesize that
      alterations in the local production of 1alpha,25(OH)2D3 may be involved in the
      tumorigenesis of breast cancer. Additionally, breast cancer may be a target for
      treatment with precursors of biologically-active vitamin D analogs.

PMID- 16886672
TI  - Novel 2-alkyl-1alpha,25-dihydroxy-19-norvitamin D3: efficient synthesis with
      Julia olefination, evaluation of biological activity and development of new
      analyzing system for co-activator recruitment.
AB  - New 2-alkyl-1alpha,25-dihydroxy-19-norvitamin D3 analogs were efficiently
      synthesized. The C2-alkyl-A-ring precursors were prepared as (3R,5R)-4-alkyl-3,5
      dihydroxycyclohexanones from (-)-quinic acid based on radical allylation at the
      C4 position of methyl (-)-quinicate. The novel CD-ring coupling partner, with the
      elongated two carbon unit, was synthesized from 25-hydroxy Grundmann's ketone,
      and applied to modified Julia olefination to construct a diene unit between the A
      ring and the CD-ring. The coupling yields, including a deprotection step, were
      moderate (47-62%). After the separation of the diastereomers based on C2
      stereochemistry using HPLC, the structure (2alpha or 2beta) was determined by 1H
      NMR studies including NOE (nuclear Overhauser effect) experiments. It was also
      found that 1H NMR chemical shifts on the A-ring showed good correlation with
      DeLuca's 2-methyl- and 2-ethyl-1alpha,25-dihydroxy-19-norvitamin D3 analogs.
      Among the synthesized 19-norvitamin D3 analogs, 2alpha-(3-hydroxypropyl)
      1alpha,25-dihydroxy-19-norvitamin D3 (8a) showed almost the same potency in
      binding to the bovine thymus vitamin D receptor (VDR) as the natural hormone (1),
      while its beta-isomer had only a 3% affinity. Both 2alpha-allyl- and 2alpha
      propyl-1alpha,25-dihydroxy-19-norvitamin D3 and their 2beta-analogs possessed a
      weak affinity for the VDR. The strong VDR ligand 8a was ca. 36-fold more potent
      in induction of HL-60 cell differentiation than 1 and, interestingly, even the
      weaker ligand, 2beta-(3-hydroxypropyl)-1alpha,25-dihydroxy-19-norvitamin D3 (8b),
      showed a 6.7-fold higher potency in cell differentiation activity than that of 1.
      Next, a novel rapid analyzing system of ligand-induced co-factor recruitment on
      VDR was developed using fluorophore labelled CoA and HCHO fixing of the complex.
      The efficiency of recruitment of co-activators would explain the discrepancy
      between the biological activity and the VDR affinity of the ligand.

PMID- 16886673
TI  - Methyl-introduced A-ring analogues of 1alpha,25-dihydroxyvitamin D3: synthesis
      and biological evaluation.
AB  - The hormonally-active metabolite of vitamin D, 1alpha,25-dihydroxyvitamin D3 (1),
      has a wide variety of biological activities, which makes it a promising
      therapeutic agent for the treatment of cancer, psoriasis and osteoporosis.
      Insights into the structure-activity relationships of the A-ring of 1 are needed
      to assist the development of more potent and selective analogues, as well as to
      define the molecular mode of action. All possible A-ring stereoisomers of 2
      methyl-1,25-dihydroxyvitamin D3 and 2,2-dimethyl-1,25-dihydroxyvitamin D3, which
      differ in stereochemistry at the C1-, C2- and C3-positions, were designed and
      efficiently synthesized by employing the convergent method. Biological evaluation
      of the analogues, in terms of the vitamin D receptor-binding affinity and HL-60
      cell differentiation-inducing activity, as well as the transcriptional potency in
      ROS 17/2.8 cells, revealed the importance of substituents at the C2-position in
      certain orientations.

PMID- 16886674
TI  - The impact of chromatin organization of vitamin D target genes.
AB  - The vitamin D receptor (VDR), the nuclear receptor for 1alpha,25-dihydroxyvitamin
      D3 (1alpha,25(OH)2D3), controls gene expression by binding discrete DNA sequences
      in promoter regions of target genes, referred to as 1alpha,25(OH)2D3 response
      elements (VDREs). Although these elements are well characterized in vitro, the
      function of VDREs in living cells in the context of chromatin is still largely
      unknown. To resolve this issue, 7 to 8 kB of the promoter regions of the primary
      1alpha,25(OH)2D3 target genes CYP24, cyclin C and p21(Waf1/Cip1) were studied by
      chromatin immunoprecipitation (ChIP) assays using antibodies against acetylated
      histone H4 (to assess the global chromatin status) and various other components
      of VDR-dependent gene activation, such as VDR, retinoid X receptor (RXR),
      coactivator (CoA) and corepressor proteins. This approach identified three to
      four functional VDREs per gene promoter. In parallel, the extended analysis of
      the gene areas, of all six members of the insulin-like growth factor binding
      protein (IGFBP) family (i.e., 10 kB of promoter, introns, exons and 10 kB of the
      downstream region) were screened in silico for putative VDR-binding sites. Gel
      shift, reporter gene and ChIP assays identified, in total, ten functional VDREs
      in the genes IGFBP1, 3 and 5 and real-time PCR confirmed that these genes are
      primary VDR targets. Taken together, these results suggest that a reasonable
      proportion of all VDR target genes, if not all, are under the control of multiple
      VDREs. These results will have an impact on the development of therapeutic
      regimes for diseases, such as cancer, that use 1alpha,25(OH)2D3 and its analogs.

PMID- 16886675
TI  - Calcitriol in the treatment of prostate cancer.
AB  - Calcitriol, the principal active metabolite of vitamin D and a naturally
      occurring hormone, showed significant antineoplastic activity in pre-clinical
      models of prostate cancer and many other tumor types. These antineoplastic
      effects were observed at calcitriol concentrations substantially above the
      physiological range. While a number of mechanisms of action have been postulated,
      the induction of apoptosis and inhibition of proliferation have been most
      extensively reported. These pre-clinical findings motivated several investigators
      to pursue a series of clinical trials to examine the potential of targeting the
      vitamin D receptor for cancer treatment using calcitriol. Initial studies tested
      daily dosing of calcitriol and showed that substantial dose escalation was not
      feasible due to hypercalciuria and/or hypercalcemia. In contrast, weekly dosing
      of calcitriol allowed substantial dose escalation without dose-limiting
      toxicities. Notably, however, the commercially available formulation of
      calcitriol exhibited nonlinear pharmacokinetics at the highest doses tested.
      While substantially higher concentrations were achieved, the maximum tolerated
      dose was not established due to this pharmacological limitation. Intermittently
      dosed calcitriol was then combined with several antineoplastic agents, including
      steroids, bisphosphonates and chemotherapeutic agents. The activity seen in a
      phase II study of weekly calcitriol plus docetaxel was particularly encouraging
      and led to the development of DN-101, a proprietary formulation designed for
      cancer treatment. DN-101 in combination with docetaxel is being evaluated in a
      placebo-controlled randomized clinical trial that has completed accrual.

PMID- 16886676
TI  - Selective inhibitors of vitamin D metabolism--new concepts and perspectives.
AB  - BACKGROUND: Levels of active vitamin D (VD) are controlled by synthesis via
      CYP27B1 and self-induced metabolism by CYP24A1. Unbalanced high CYP24A1
      expression due to induction by diverse endogenous compounds and xenobiotics, and
      amplification found in various tumours, might lead to local VD deficiency,
      thereby causing/reinforcing disorders. MATERIALS AND METHODS: Using primary human
      keratinocytes, CYP24A1 expression was examined at the mRNA level by dot-blot and
      Northern blot hybridization, and at the enzyme activity level by analysing HPLC
      profiles from incubations with 3H-labelled VD metabolites. RESULTS: We have
      developed a one-step protocol to screen test compounds for potent inhibition of
      CYP24A1 along with selectivity over CYP27B1 and adequate metabolic stability.
      These inhibitors amplified hormone levels and, thereby, its function, indicated
      by increased CYP24A1 expression. Moreover, they stabilized the expression of a
      CYP24A1 splice variant, possibly serving as a buffer of VD metabolites. In
      addition, a low abundant, constitutive 24-hydroxylase, active in the low
      nanomolar range is described. CONCLUSION: Selective CYP24A1 inhibitors could
      herald a new era for vitamin D research, as well as for therapeutic application.
      Inhibitors may be used as single entities or in combination with low doses of
      potent analogs to prevent and treat various defects of growth and
      differentiation, and neuro-immuno-endocrine disorders.

PMID- 16886677
TI  - Effects of 1alpha,25-dihydroxyvitamin D3 in human colon cancer cells.
AB  - Colorectal cancer is a major health problem worldwide. Epidemiological studies
      and work on experimental animals strongly suggest a protective effect of
      1alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3) against colon neoplasia. 1,25(OH)2D3
      is a pleiotropic hormone that has multiple actions in the organism. By binding to
      the widely expressed high affinity vitamin D receptor (VDR) it regulates the
      transcription rate of many genes. Other non-genomic effects of 1,25(OH)2D3 also
      appear to modulate the physiology of numerous cell types. Human normal and cancer
      colon epithelial cells express VDR and the key enzymes involved in 1,25(OH)2D3
      synthesis and degradation and are, thus, responsive to the hormone. 1,25(OH)2D3
      inhibits proliferation, induces differentiation and sometimes the apoptosis of
      human colon cancer cells. A great variety of mechanisms and signaling pathways
      are involved. Since VDR mediates most, if not all, 1,25(OH)2D3 actions, the
      control of VDR expression is a crucial aspect of 1,25(OH)2D3 biology. Here, the
      molecular mechanisms underlying the actions of 1,25(OH)2D3 are reviewed and the
      repression of the VDR gene by the transcription factor SNAIL in human colon
      cancer cells is discussed. Understanding these mechanisms may provide the basis
      for the potential use of this hormone and its non-hypercalcemic derivatives in
      the prevention and treatment of colon cancer.

PMID- 16886679
TI  - The association of solar ultraviolet B (UVB) with reducing risk of cancer:
      multifactorial ecologic analysis of geographic variation in age-adjusted cancer
      mortality rates.
AB  - BACKGROUND: Solar ultraviolet B (UVB) irradiance and vitamin D are associated
      with reduced cancer mortality rates. However, the previous ecologic study of UVB
      and cancer mortality rates in the U.S. (Grant, 2002) did not include other risk
      factors in the analysis. MATERIALS AND METHODS: An ecologic study was performed
      using age-adjusted annual mortality rates for Caucasian Americans for 1950-69 and
      1970-94, along with state-averaged values for selected years for alcohol
      consumption, Hispanic heritage, lung cancer (as a proxy for smoking), poverty,
      degree of urbanization and UVB in multiple regression analyses. RESULTS: Models
      were developed that explained much of the variance in cancer mortality rates,
      with stronger correlations for the earlier period. Fifteen types of cancer were
      inversely-associated with UVB. In the earlier period, most of the associations of
      cancer death rates with alcohol consumption (nine), Hispanic heritage (six), the
      proxy for smoking (ten), urban residence (seven) and poverty (inverse for eight)
      agreed well with the literature. CONCLUSION: These results provide additional
      support for the hypothesis that solar UVB, through photosynthesis of vitamin D,
      is inversely-associated with cancer mortality rates, and that various other
      cancer risk-modifying factors do not detract from this link. It is thought that
      sun avoidance practices after 1980, along with improved cancer treatment, led to
      reduced associations in the latter period. The results regarding solar UVB should
      be studied further with additional observational and intervention studies of
      vitamin D indices and cancer incidence, mortality and survival rates.

PMID- 16886678
TI  - Expression analysis of CYP27B1 in tumor biopsies and cell cultures.
AB  - There is evidence for alternative splicing as a prevalent mechanism both in
      normal human cells and cancer cells. Alternative splice variants of the gene
      encoding the human 25-hydroxyvitamin-D3-1alpha-hydroxylase (CYP27B1) in human
      glioblastoma were recently reported. Using combined nested and touchdown PCR,
      full length CYP27B1 as well as several splice variants were cloned. Here, this
      approach was used to analyze the expression of CYP27B1 and its splice variants in
      normal tissues, tumor tissues and cell cultures. Expression of CYP27B1 was found
      in all tumor tissues. The expression of CYP27B1 was also found in several normal
      tissues including lung, kidney, placenta, thymus and stomach and in derived cell
      cultures. The expression of splice variants of CYP27B1 were detected in 1 out of
      3 tested brain samples, with no evidence for the expression of normal CYP27B1.

PMID- 16886680
TI  - Antiproliferative activity of vitamin D compounds in combination with
      cytostatics.
AB  - Calcitriol is a potent antiproliferative agent against various tumour cells in
      vitro. Here, the results of a study on vitamin D compounds (calcitriol's
      analogues PRI-1906 and PRI-2191) as potential agents in combined antitumour
      therapy in vitro are presented. Applying antiproliferative SRB and MTT assays,
      the growth inhibitory effects of the vitamin D compounds, applied alone or in
      combination with either cisplatin or doxorubicin, were measured. The following
      cancer cell lines were employed: A549 (human non-small cell lung carcinoma), B16
      (murine melanoma), CCRF, HL-60 (human leukaemia), SW707 (human colon cancer), MCF
      7, T47D (human breast cancer), WEHI-3 (mouse leukaemia) and normal cells: BALB
      3T3 (normal murine fibroblast cell line). It was shown that the treatment of
      tumour cells, which are sensitive to vitamin D compounds, with the combination of
      vitamin D compounds and cytostatics decreased the inhibitory concentration 50%
      (IC50) values compared with the effects of the cytostatics applied alone.

PMID- 16886681
TI  - Clusterin (CLU) and melanoma growth: CLU is expressed in malignant melanoma and
      1,25-dihydroxyvitamin D3 modulates expression of CLU in melanoma cell lines in
      vitro.
AB  - BACKGROUND: The glycoprotein clusterin (CLU) has two known isoforms generated in
      human cells. A nuclear form of CLU protein (nCLU) is pro-apoptotic, while a
      secretory form (sCLU) is pro-survival. CLU expression has been associated with
      tumorigenesis and the progression of various malignancies. MATERIALS AND METHODS:
      The expression of CLU was studied immunohistochemically in paraffin sections of
      primary cutaneous malignant melanomas, metastases of malignant melanomas and
      acquired melanocytic naevi. Using PCR and Western blotting, the expression of CLU
      was also investigated in various vitamin D-responsive (MeWo, SK-MEL-28) and
      vitamin D-resistant melanoma cell lines (SK-MEL-5, SK-MEL-25), as well as in
      normal human melanocytes (NHM), along with 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]
      treatment. RESULTS: In contrast to acquired melanocytic naevi, CLU
      immunoreactivity was found in primary cutaneous malignant melanomas and
      metastases of malignant melanomas in situ. Both CLU protein and RNA were detected
      in melanoma cell lines and NHM. Treatment with 1,25(OH)2D3 modulated CLU's
      expression in vitamin D-responsive but not in -resistant melanoma cell lines.
      CONCLUSION: CLU may be of importance for the progression of malignant melanoma.
      The growth regulatory effects of 1,25(OH)2D3 in melanoma cell lines may, at least
      in part, be mediated via modulation of CLU expression.

PMID- 16886682
TI  - Vitamin D analogs and coactivators.
AB  - The secosteroid hormone 1alpha,25-dihydroxyvitamin D3 [1,25-(OH)2D3] has potent
      antiproliferative and prodifferentiating actions on a wide variety of normal as
      well as malignant cell types. Strong calcemic effects obstruct the actual
      application of 1,25-(OH)2D3 for the treatment of hyperproliferative disorders
      such as cancer. To overcome this problem, structural analogs of 1,25-(OH)2D3 have
      been designed with a clear dissociation between antiproliferative and calcemic
      effects. This review focuses on the molecular mode of action of different 1,25
      (OH)2D3 analogs and, in particular, on the recruitment of cofactor molecules to
      the vitamin D receptor by these analogs.

PMID- 16886683
TI  - UV radiation and cancer prevention: what is the evidence?
AB  - The health benefits of sunlight and the risk of skin cancer from UV exposure are
      still controversial. The literature was analyzed in terms of reviews, controlled
      and epidemiological studies for the relationships between sunshine exposure and
      overall cancer mortality, as well as mortality from cancer of the prostate, colon
      and breast. The residential and/or occupational sun exposure rate seemed to be
      positively correlated with a lower risk of overall morality due to organ cancer.
      A normal vitamin D status appeared to be an important precondition, via the local
      and autocrine synthesis of 1,25(OH)2D3 in the target tissues. The vitamin D
      hormone system is necessary for cell proliferation and differentiation; different
      types of vitamin D receptor gene polymorphism seemed to be associated with cancer
      cell growth. The health benefits of sunlight appear to outweigh the risk of skin
      cancer. However, the optimal UV exposure, the target level of circulating vitamin
      D, and whether vitamin D is the only pathway are still undetermined.

PMID- 16886684
TI  - Insufficient vitamin D supply as a possible co-factor in colorectal
      carcinogenesis.
AB  - Vitamin D, the "sunshine vitamin", may play a role in the development of
      colorectal cancer. In a prospective open study, the plasma levels of 25
      hydroxyvitamin D [25(OH)D], the marker for sufficient or insufficient vitamin D
      supply, were determined in three groups of patients whose diagnoses were
      confirmed by colonoscopy: healthy individuals (n = 239), patients with colorectal
      adenoma (n = 203) and with carcinoma (n = 98). In order to assess other factors
      such as nutrition, sunlight exposure and physical activity as co-variates for the
      risk of colorectal cancer, the individuals completed a questionnaire. Patients
      with colorectal cancer (CRC) had significantly decreased plasma 25(OH)D levels (p
      < 0.001) compared to the controls in contrast to patients with adenomas, who had
      lower levels exclusively in the winter (p = 0.01). When analyzed by the Kruskal
      Wallis test, the groups of patients with adenomas (p = 0.03) and colorectal
      carcinomas (p < 0.0001) had significantly different mean plasma values compared
      to the controls. The plasma 25(OH)D levels showed an inverse correlation to the
      UICC stages of CRC; however, the differences were not significant. Patients with
      CRC were significantly older than the controls, but regression analysis showed no
      significant correlation between the plasma 25(OH)D levels and age, and the
      influence of age on the plasma levels of 25(OH)D was minimized in a group of
      individuals over 65 years of age, in which the patients with CRC had
      significantly decreased plasma levels of 25(OH)D in the winter. About one-half of
      the individuals with normal colonic mucosa had plasma 25(OH)D levels below 25
      microg/l (the normal range) and one-third even had plasma levels below 20
      microg/l. Regression analysis showed a significant influence of age on plasma
      25(OH)D levels in healthy individuals, of physical activity in patients with
      adenomas and of season in patients with CRC. Other covariates, such as nutrition
      or sunlight exposure, had no significant influence on plasma 25(OH)D. In
      conclusion, an insufficient vitamin D supply might act as a co-factor in
      colorectal carcinogenesis.

PMID- 16886685
TI  - 1alpha,25-Dihydroxyvitamin D3 modulates the response of human keratinocytes to
      ionizing radiation exposure.
AB  - BACKGROUND: Exposure of human skin to ionizing radiation may result in various
      effects such as inflammation, keratosis, fibrosis and cancer. 1alpha,25
      Dihydroxyvitamin D3 (1alpha,25(OH)2D3), the biologically active metabolite of
      vitamin D, has been shown to exert pleiotropic effects on the skin. The aim of
      the study was to evaluate the effect of 1alpha,25(OH)2D3 on the radiation
      response of human keratinocytes. MATERIALS AND METHODS: Keratinocytes (HaCaT),
      either untreated or pretreated with 1alpha,25(OH)2D3, were irradiated with 0-7.5
      Gy. Growth curves were generated to determine cell proliferation. Cell survival
      was examined using a clonogenic assay. The cell surface expression of adhesion
      molecules was investigated by flow cytometry. RESULTS: The cell growth and
      clonogenic survival of irradiated keratinocytes were both significantly increased
      by 1alpha,25(OH)2D3. Ionizing radiation caused an up-regulation of the cell
      surface expression of intercellular adhesion molecule-1 (ICAM-1) and integrins
      beta1 (CD29), alpha2 (CD49b), alpha5 (CD49e) and alpha6 (CD49f) in keratinocytes,
      which was inhibited by 1alpha,25(OH)2D3. CONCLUSION: The data suggest that
      1alpha,25(OH)2D3 may be a promising agent to modify the radiation reaction, thus
      offering new options in radiotherapy and oncology.

PMID- 16886686
TI  - Cutaneous photosynthesis of vitamin D: an evolutionary highly-conserved endocrine
      system that protects against environmental hazards including UV-radiation and
      microbial infections.
AB  - Phytoplankton and zooplankton have been producing vitamin D for more than 500
      million years. While the function of vitamin D in the physiology of lower non
      vertebrate organisms is not well understood, it is known that most vertebrates
      need vitamin D to develop and maintain a healthy mineralized skeleton. However,
      recent findings have demonstrated that 1,25(OH)2D, the biologically-active
      vitamin D metabolite, exerts a multitude of important physiological effects
      independently of the regulation of calcium and bone metabolism. These new
      functions of vitamin D include protection against cancer and other diseases in
      various tissues. In this review, current knowledge of an additional new function
      of the cutaneous photosynthesis of vitamin D, that has recently emerged, is
      summarized: the role of vitamin D as an evolutionary highly-conserved endocrine
      system that protects the skin and other tissues against environmental hazards,
      including ionizing and UV-radiation, microbial infections and oxidative stress,
      is discussed.

PMID- 16886687
TI  - Modulation of MAPK ERK1 and ERK2 in VDR-positive and -negative breast cancer cell
      lines.
AB  - 1alpha-25-Dihydroxyvitamin D3 (calcitriol), the biologically active metabolite of
      vitamin D, is known to regulate calcium and phosphate levels in bone metabolism.
      It is also known to influence proliferation and differentiation in carcinoma
      cells mediated by the vitamin D receptor (VDR). The antiproliferative effects of
      calcitriol are believed to be mediated by the nuclear pathway via binding the
      activated receptor to vitamin D-responsive elements. This induces the vitamin D
      responsive genes. Another possible pathway might be the MAPK-cascade or rapid
      response pathway. The interaction of calcitriol and the MAP-kinase-cascade was
      evaluated on VDR-positive MCF-7 cells and VDR-negative MDA-MB-231 breast cancer
      cells. The cells were incubated with calcitriol solution at 10(-7) M and 10(-9)
      M, or ethanol as controls, for up to 48 h. The effects of calcitriol were
      measured by semi-quantitative Western blotting. Calcitriol stimulated the MAP
      kinases ERK1 and ERK2. A biphasic activation was found for calcitriol in VDR
      positive cells after incubation for 5 to 20 min and from 2 to 24 h. However,
      early activation of ERK1 and ERK2 was also demonstrated in VDR-negative cells. In
      the controls, ethanol also induced the MAPK-cascade at 5 to 10 min. Calcitriol
      induction was demonstrated after incubation from 2 to 24 h. In conclusion, it
      seems that the early induction of the MAPK-cascade was independent of the VDR. A
      calcitriol-induced MAPK activation was shown after 4 h, which may have been
      caused by activation of the nuclear receptor pathway.

PMID- 16886689
TI  - [Delirium in critically ill children in a paediatric intensive care unit].
AB  - Two critically ill girls, aged 2.3 years and 3.5 years respectively, developed
      delirium in the Paediatric Intensive Care Unit (PICU). The first child, admitted
      with meningococcal meningitis and septic shock with respiratory failure, suffered
      from hyperactive delirium which started 2 hours post-extubation. The second
      child, admitted due to an exacerbation of cystic fibrosis with the threat of
      respiratory failure, suffered from hypoactive delirium with regression,
      inconsolability, dyspraxia and dysphasia. Both patients responded well to a
      single intravenous dose of haloperidol. Although delirium occurs in critically
      ill children, it often goes unrecognized, particularly in its hypoactive form. It
      should nevertheless be considered as a medical emergency, particularly in a PICU
      setting, and should be treated accordingly. Physicians are generally reluctant to
      consider psychopharmacological treatment of childhood delirium. Haloperidol is
      considered as the drug of choice, but risperidone can also be used successfully.

PMID- 16886688
TI  - Vitamin D--metabolism in the human breast cancer cell line MCF-7.
AB  - BACKGROUND: The three main vitamin D metabolizing enzymes, vitamin D3-25
      hydroxylase (25-OHase, 25-hydroxylase), 25-hydroxyvitamin D3-1alpha-hydroxylase
      (1alpha-OHase, 1alpha-hydroxylase) and 25-hydroxyvitamin D3-24-hydroxylase (24
      OHase, 24-hydroxylase), have been described in malignant breast tissue. This in
      vitro study aimed to obtain more information regarding the regulation of these
      enzymes in the human breast cancer cell line MCF-7. MATERIALS AND METHODS:
      Vitamin D receptor (VDR)- positive MCF-7 cells in culture were stimulated with
      the vitamin D metabolites vitamin D3, 25-hydroxyvitamin D3 and 1,25
      dihydroxyvitamin D3 for 24, 48; 72 and 96 hours in physiological and
      supraphysiological concentrations. The expressions of 25-hydroxylase, 1alpha
      hydroxylase and 24-hydroxylase and their changes after stimulation were assessed
      by real-time PCR. RESULTS: The expression of 25-hydroxylase was slightly
      influenced by vitamin D3. The expression of 1alpha-hydroxylase was induced after
      stimulation with vitamin D3 and 25-hydroxyvitamin D3. Stimulation with 1,25
      dihydroxyvitamin D3 markedly increased the expression of 24-hydroxylase time- and
      dose-dependently. CONCLUSION: Our results demonstrated that MCF-7 cells are able
      to regulate the expression of 24-hydroxylase. This might be a mechanism for these
      tumor cells to protect themselves against the antiproliferative and apoptosis
      inducing effects of calcitriol.

PMID- 16886690
TI  - [Specific dermatoses of pregnancy].
AB  - Dermatoses related to pregnancy or the postpartum period are known as the
      specific dermatoses of pregnancy. These dermatoses include (a) pemphigoid
      gestationis (synonym: herpes gestationis), (b) polymorphic eruption of pregnancy
      (synonym: pruritic urticarial papules and plaques of pregnancy; PUPPP), (c)
      prurigo of pregnancy and (d) pruritic folliculitis of pregnancy. Of these
      disorders, only pemphigoid gestationis has a known cause: an allogeneic immune
      reaction of the mother to the placental basal membrane. Itching or an itchy skin
      eruption is often the main symptom ofa dermatosis of pregnancy. During the
      diagnostic process, the possibility of a pre-existing or de novo skin disorder
      unrelated to the pregnancy should be considered. Correct diagnosis is important
      for the choice of treatment and for the prognosis of mother and child, because
      some dermatoses of pregnancy, such as pemphigoid gestationis, constitute a health
      risk.

PMID- 16886691
TI  - [Distraction osteogenesis in the head and neck region].
AB  - Distraction osteogenesis is used in oral and maxillofacial surgery for the
      purpose of lengthening or widening an upper or lower jaw or to reposition the jaw
      to such an extent as cannot be achieved with normal osteotomy. This technique
      moves the parts of an osteomised bone slowly apart. Subsequently, new trabecular
      bone growth occurs between the separate bone parts that is then turned into bone
      with a normal mineralised architecture. Extraoral distractors can be fitted,
      activated, positioned and removed fairly easily. Distractors for intraoral
      placement do not cause any extraoral scars and are less burdensome in their daily
      use. Some distractors can impede access to the larynx and the trachea. For
      elective surgical procedures, the accessibility of the larynx can be judged with
      a laryngoscope for the induction and ending of anaesthesia. Should the intraoral
      or extraoral distractors form any obstruction in this process, then they should
      be removed. The alternatives are fibroscopic intubation and emergency
      tracheotomy.

PMID- 16886692
TI  - [Central catheters should be removed immediately if bacteraemia occurs].
AB  - No randomised controlled study has been conducted into the correct treatment of
      catheter-related bacteraemia infections. This is due to the fact that true
      bacteraemia is difficult to differentiate from catheter contamination. Experience
      in the treatment of patients who do not have bacteraemia is therefore often
      incorrectly extrapolated to patients who do have bacteraemia with a central
      catheter in situ. Removing the central catheter can reduce the risk of
      complications of bacteraemia.

PMID- 16886693
TI  - [Bacteraemia in a patient with a central venous line is not a reason for
      immediate removal of the line].
AB  - Fever and the presence of a central venous catheter is a frequent combination in
      (critically) ill patients, but has a low predictive value for catheter-related
      sepsis. Therefore, the immediate removal of a central venous line is often
      unnecessary, even if there is fear for endocarditis when Staphylococcus aureus is
      present. Recent studies have shown that the odds ratio for this complication is
      rather low.

PMID- 16886694
TI  - [Diagnostic image (282). A woman with invalidating hip complaints].
AB  - A 40-year-old woman with a five-year history of rheumatoid arthritis experienced
      progressive pain of the left hip due to protrusio acetabuli.

PMID- 16886695
TI  - [Efficacy and adverse reactions of antipsychotics for neuropsychiatric symptoms
      in dementia: a systematic review].
AB  - OBJECTIVE: To assess the efficacy and adverse reactions of typical and atypical
      antipsychotics in the treatment of neuropsychiatric symptoms in dementia, and to
      examine the evidence for the cerebrovascular events warning for atypical
      antipsychotics. DESIGN: Systematic review. METHOD: Using Medline, Cinahl,
      PsyclNFO, Embase and the Cochrane central register of controlled trials (1980
      2005), double-blind randomized controlled trials with intention-to-treat analysis
      were selected, which evaluated efficacy and adverse reactions of antipsychotics
      in the treatment of neuropsychiatric symptoms in dementia. The studies underwent
      a standardised validity assessment. RESULTS: After screening 950 studies, 14
      studies on the effect of haloperidol, risperidone, olanzapine, quetiapine,
      tiapride, loxapine and perphenazine were selected. In 7 out of 10 studies,
      haloperidol, risperidone and olanzapine appeared to be more effective than
      placebo in the treatment of aggression and psychosis. Direct comparison between
      typical and atypical antipsychotics revealed no statistically significant
      difference. The most common adverse reactions were extrapyramidal symptoms and
      somnolence. These adverse reactions were less frequent with low-dose risperidone
      than with haloperidol or olanzapine, but risperidone and olanzapine were found to
      be associated with a higher risk of cerebrovascular events in two studies.
      CONCLUSION: The efficacy of typical and atypical antipsychotics is comparable,
      but only low-dose risperidone seems to be associated with fewer (extrapyramidal)
      side effects. The adverse reactions are inadequately described in the published
      data and consequently the warning of an increased risk of mortality could not be
      confirmed.

PMID- 16886696
TI  - [Hypoglycaemic coma due to falsely elevated glucose values in a patient with
      diabetes mellitus and peritoneal dialysis].
AB  - A 45-year-old female diabetes-mellitus patient on peritoneal dialysis was
      admitted because of vertigo. During her stay in hospital she developed a comatose
      condition with abnormal head posture and deviation ofthe eyes to the left.
      Capillary blood from the fingertip showed a glucose value of 15.4 mmol/l.
      However, the automatically obtained glucose value delivered with a blood-gas
      analysis was found to be 1.2 mmol/l. The neurological state of the patient
      normalised fully after intravenous glucose administration. The glucose values
      were falsely elevated because the patient used a peritoneal dialysis fluid at
      night which contained icodextrin as an osmotic agent. Metabolites of icodextrin
      can influence blood-glucose measurements taken using analyzers that depend on the
      enzyme glucose dehydrogenase. To prevent potentially life-threatening situations,
      the use of an adequate glucose meter is of paramount importance.

PMID- 16886697
TI  - [Acute anaemia in a Vietnamese patient with alpha-thalassaemia and a parvovirus
      infection].
AB  - A 14-year-old girl of Vietnamese descent with an unremarkable medical history
      presented with haemodynamic shock due to severe anaemia. This was caused by an
      aplastic crisis resulting from the combined effects of a Parvovirus infection and
      HbH disease. The HbH disease was a result of compound heterozygosity for the
      South East Asia (SEA) deletion and the Constant Spring mutation in the genes
      coding for alpha-globin chains (HbH/Hb Bart's). The girl had multiple blood
      transfusions and recovered. Family investigation revealed that, in addition to
      these 2 mutations in the alpha-globin gene, some family members also carried the
      3.7-kb deletion of the alpha-globin gene, a mutation in the beta-globin gene
      resulting in HbE, and a novel mutation of unknown clinical significance in the
      beta-globin gene. This case demonstrates that essentially asymptomatic
      carriership of thalassaemia can have serious consequences when coupled with a
      concurrent infection.

PMID- 16886698
TI  - [New study evaluating online haemodiafiltration for the reduction of
      cardiovascular morbidity and mortality in patients undergoing chronic
      haemodialysis].
AB  - Removal of uraemic toxins can be increased by online haemodiafiltration. At
      present, it is unclear whether online haemodia-filtration ultimately improves
      clinical outcomes in chronic haemodialysis patients. The Dutch 'Convective
      transport study' (CONTRAST) is an ongoing trial comparing standard haemodialysis
      with online haemodiafiltration. This randomised controlled trial will provide
      substantial clinical evidence on the effects of haemodiafiltration on fatal and
      non-fatal cardiovascular events and all-cause mortality, compared with standard
      haemodialysis.

PMID- 16886699
TI  - [Diabetes mellitus: simple classification and corresponding treatment].

PMID- 16886700
TI  - Prevalence and costs of parkinsonian syndromes associated with orthostatic
      hypotension.
AB  - OBJECTIVE: To measure the frequency of and direct costs related to parkinsonian
      syndromes associated with orthostatic hypotension (OH). PATIENTS/METHODS:
      Patients over 45 years using at least one antiparkinsonian drug (excluding
      piribedil or anticholinergics prescribed alone) were identified from the Haute
      Garonne Social Security prescription database and separated in two groups
      according to simultaneous prescription (OH group) or not (control group) of drugs
      for orthostatic hypotension. Direct medical costs were analysed retrospectively,
      over a 6-month period, from the health care payer's perspective. RESULTS: Eighty
      eight patients (9.1%) out of 971 parkinsonian also received antihypotensive
      drugs. Direct medical costs were significantly higher in OH than in control group
      (4.425 vs. 3.074 Euro/patient/6 months, p < 0.05). Beside hospitalisation and
      ancillary cares, drugs accounted for highest expenses (989 vs. 781 Euro/patient/6
      months in control group) since use of controlled-release levodopa formulations or
      dopamine agonists was higher in OH group. CONCLUSION: Occurrence of OH is
      associated with higher medical expenditure in parkinsonian syndromes.

PMID- 16886702
TI  - [Patterns of non steroidal anti-inflammatory drug use in ambulatory care].
AB  - The aim of this study was to discuss the patterns of non steroidal anti
      inflammatory drug (NSAID) use in general population. We identified NSAID's users
      from the French Health Insurance System claims database covering more of the
      population in the Midi-Pyrenees area (southwest of France), if they have received
      at least one NSAID in June 2003. We discussed this population according to the
      NSAID used, to their demographic characteristics and to other drugs delivered in
      the period. Our study shows different patterns of use according to each NSAID.
      For example, users of ibuprofen or tiaprofenic acid were younger and less
      frequently exposed to "gastroprotective" drugs, users of coxibs were older and
      more frequently exposed to drugs increasing the risk of bleeding. This study
      confirms the wide use of NSAIDs and describes their target population. It
      underlines the interest of Health Insurance System Database for better knowledge
      of drug use in ambulatory care in France.

PMID- 16886701
TI  - [Medico economic analysis in first line chemotherapy in advanced lung cancer].
AB  - Our objective was to analyse economic consequences modifying first line
      chemotherapy in treatment non small cell lung cancer IIIB-IV. Therefore a cost
      minimisation has been performed. Resources consumption were collected in a
      Pneumology department for 21 patients receiving previously mitomycine-ifosfamide
      platin and for the 21 first patients receiving vinorelbine-platin, new patients
      diagnosed during year 2001. Costs were derived from hospital accounting system,
      economic analysis performed from the hospital and from the health French system
      points of view. Activity Synthetic Index point decrease of 2.9% per patient in
      vinorelbine-platin versus mitomycine-ifosfamide-platin, as an increase of 64.6%
      of hospital drug spending is registered (1,893 Euro versus 1,150 Euro) and an
      over cost of 15.7% for health French system (14179 Euro versus 12,257 Euro).
      Whatever the perspective of economic analysis, vinorelbine-platin arm is
      dominated by the mitomycine-ifosfamide-platin arm.

PMID- 16886703
TI  - [Heart rate, a major prognostic factor of cardiovascular risk].
AB  - The prognostic value of heart rate (HR) was analysed based on the reports from
      the literature in the general population and in patients with coronary artery
      disease (CAD). Multivariate analyses showed that elevated resting HR was found to
      be an independent predictor of total and cardiovascular mortality. The behaviour
      of HR during exercise testing was predictive of sudden death. The beneficial
      effects of betablockers in post-infarction patients are well established. Calcium
      channel blockers that increase resting HR are associated with a deleterious
      effect on mortality. Therefore, resting HR should not be overlooked in risk
      stratification of CAD patients. Reduction of resting HR should be viewed as an
      attractive therapeutic target in CAD patients.

PMID- 16886704
TI  - [A complete clinical trial register is already a reality in the paediatric
      field].
AB  - Clinical trials have a fundamental role in promoting an evidence based use of
      drugs in adults and in children. However, it is often difficult to identify the
      few paediatric studies carried out and to thus implement knowledge derived from
      them. Furthermore, studies that are stopped prematurely or that have
      insignificant or negative results often remain unpublished, leading to
      duplication of effort by researchers, waste of resources and concealment of
      potentially toxic risks. The European Community decided to support the
      development of a European register of clinical trials in children as part of the
      Fifth Framework Thematic Programme "Quality of Life" in 2002. The project DEC-net
      is coordinated by the Laboratory of Mother and Child Health of the Mario Negri
      Institute for Pharmaceutical Research in Milan and currently involves members of
      four countries; France, Italy, Spain and the United Kingdom. It is unique in that
      it is the first population oriented clinical trial register. Such a register
      represents a useful source for planning new studies, promoting communications and
      collaborations between researchers, facilitating patient access and recruitment
      into trials, preventing trial duplication and inappropriate funding and
      identifying the therapeutic needs of children that remain neglected. It will also
      allow for active monitoring of new or evolved knowledge of drug therapies.

PMID- 16886705
TI  - Glycoprotein changes in non-insulin dependent diabetic rats: effect of N-benzoyl
      D-phenylalanine and metformin.
AB  - The effect of N-benzoyl-D-phenylalanine (NBDP) and metformin on neonatal
      streptozotocin (nSTZ) induced diabetes has been studied on plasma and tissue
      glycoproteins. In some pathological conditions, such as cancer, rheumatoid
      arthritis and diabetes, there is an abnormal glycosylation of acute phase serum
      proteins. As most serum proteins are produced in the liver, we have examined
      glycoprotein metabolism in diabetic condition. To induce non-insulin-dependent
      diabetes mellitus (NIDDM) a single dose of streptozotocin (100 mg/kg body weight)
      was injected into two day old rats. After 10-12 weeks, rats weighing above 150 g
      were selected for NIDDM model. In these rat, blood glucose and plasma
      glycoproteins were significantly increased whereas plasma insulin was
      significantly decreased. There was a significant decrease in the level of sialic
      acid and elevated levels of hexose, hexosamine and fucose in tissues. Oral
      administration of NBDP and metformin to diabetic rats decreased blood glucose and
      plasma glycoproteins. Plasma insulin and tissue sialic acid were increased
      whereas tissue concentrations of hexose, hexosamine and fucose were near normal.
      Our study suggests that NBDP and metformin possess a significant beneficial
      effect on glycoproteins in addition to their antidiabetic effect.

PMID- 16886706
TI  - [Botanicus and phytotox: data base of plant toxicology. Interest in emergency
      toxicology and in phytovigilance].
AB  - The purposes of this project were to summarize more than 279 standard botanical
      names and their 2294 vernacular ones (French common names, Arabic common names
      and Moroccan common names) for the first part of database named "Botanicus". The
      second part of this data base named "Phytotox", concerns relevant toxic data of
      120 plants available in Mediterranean region. The database will be useful for
      emergency physicians, particularly of Maghreb and French- speaking countries.
      Botanicus and Phytotox permit to assist them in providing fast and appropriate
      answers to questions concerning adverse effects associated with plant use.

PMID- 16886707
TI  - [Treatment of bronchial superinfections: data related to stability of antibiotics
      in portable pumps].
AB  - INTRODUCTION: Given many data about the stability of antibiotics in portable pump
      (elastomer) are lacking, this study was designed to make a point about available
      data and to evaluate the stability of antibiotics when exposed to temperature
      within 35 degrees C (average temperature measured in real conditions of use).
      MATERIAL AND METHODS: First, to collect information about the stability of
      antibiotics in portable pump and to confront them with the local antibiotics
      protocols dedicated to the treatment of bronchial superinfection in patients with
      cystic fibrosis; second, to evaluate the stability of piperacillin associated
      with tazobactam at 35 degrees C. RESULTS: While measured concentrations in
      tazobactam did not show significant variation during the study, piperacillin
      measurements showed a major reduction of concentration (up to 33%), both time and
      concentration related to. DISCUSSION: Such information must be pointed out to
      prescribers and patients to ensure a cold accumulator is placed in the pump
      carrying-bag and to limit the duration of infusion to 24 h with a single pump.
      CONCLUSION: This experimental program will keep on going with the stability study
      of both ticarcillin and cefsulodin in portable pump.

PMID- 16886708
TI  - [Chemical submission: a literature review].
AB  - The aim of this review is to describe the present knowledge about chemical
      submission. The number of scientific publications on this phenomenon has
      increased over the last 10 years. Perpetrators choose drugs which act rapidly,
      produce desinhibition, sedation, and anterograde amnesia during the abuse.
      Ethanol and benzodiazepines are the most frequently used. A few drugs, including
      flunitrazepam and gamma-hydroxybutyric acid (GHB), have received widespread media
      coverage. Toxicological investigations on blood, urine or hair samples allow to
      detect the substance used. Every effort should be made to collect appropriate
      specimens as quickly as possible. Gas chromatography-mass spectrometry is at
      present the most appropriate analytical method to detect these drugs in a
      biological specimen.

PMID- 16886709
TI  - [Analgesic/Antipyretic treatment: ibuprofen or acetaminophen? An update].
AB  - Because of the adverse effects associated with aspirin, especially Reye's
      syndrome in children, practitioners currently use as first line therapy drugs
      such as ibuprofen or acetaminophen. Their pharmacokinetic characteristics are not
      quite identical: both are absorbed rapidly and have high bioavailability,
      however, unlike acetaminophen, ibuprofen is characterized by high plasma protein
      binding and a limited distribution volume. Both drugs are metabolized essentially
      in the liver into inactive hydroxylated or glucoronidated metabolites by
      conjugation but acetaminophen is also transformed into an oxidation compound-
      normally reduced by glutathione--which, in the case of acute overdosing with
      depletion of endogenous glutathione stores, may lead to severe hepatotoxicity.
      Old age and light to moderate renal or hepatic failure do not significantly
      modify their pharmacokinetic parameters, and thus do not call for dose
      adjustment. Clinical trials have shown both drugs to have comparable efficacy on
      pain and fever, with perhaps a slight advantage for ibuprofen. In practice, the
      choice will depend on the prescription habits of the practitioner, patient's (or
      parents') preferences and, above all, the pathological context and possible
      contra-indications.

PMID- 16886710
TI  - [The optimal dosing times of corticoids].
AB  - The therapeutic use of cortisol and its derivatives, anti-inflammatory
      corticoids, sets delicate problems to resolve because of cortisol's physiological
      roles and its circadian rhythms. Cortisol and the majority of its derivatives
      have desirable and undesirable effects that are time-related administration. The
      chronotherapeutic optimisation to increase desirable effects and safety of
      corticoids is shown in the treatment of adrenocortical failure, congenital
      adrenal hyperplasia and asthma. The knowledge of physiological and
      physiopathological rhythms of asthma permitted to realize oral treatment
      optimisation by using a number of corticoids. This knowledge puts in a prominent
      position the advantages of ciclesonide: a new inhaled corticoid. A chronobiologic
      approach could be used in a classic optimisation which involves a molecule
      modification and inhalation like routes of administration.

PMID- 16886711
TI  - [Analysis of antiretroviral drugs-induced adverse effects].
AB  - In 1999, The Regional Center of Pharmacogilance and the Department of Infectious
      Disease of the Toulouse University Hospital set up a system to improve the data
      collection about antiretroviral-induced adverse reactionss (ADRs). From November
      1999 to April 2003, a resident of pharmacovigilance collected ADRs reported with
      antiretroviral drugs during 2 weekly medical consultations. A total of 613 ADRs
      corresponding to 428 patients were reported, classified as "non serious" in 88.6%
      of cases and required the withdrawal of suspected drugs in 57% of cases. Our data
      show an improvement of antiretroviral drug-induced ADRs reporting.

PMID- 16886712
TI  - [Interpretation of aspirin plasma concentration in the acute phase of Kawasaki
      disease].

PMID- 16886713
TI  - U.S. physician workforce forecasting: a tale of two states.
AB  - Physician workforce forecasting in the U.S. has returned to preeminence in the
      recent past. With the publication of the federal Council on Graduate Medical
      Education's Sixteenth Report: Physician Workforce Policy Guidelines for the
      United States, 2000-2020, efforts have begun to examine specialty- and geography
      specific forecasts to determine the extent to which the projected national
      shortage of physicians will affect particular specialties and populations in
      particular areas. This article begins with a brief history of physician workforce
      forecasting in the U.S. over the past 25 years and summarizes the findings of two
      state-specific attempts to forecast physician supply and demand in the coming
      years. Discussions of the findings from the two studies as well as a brief
      commentary on how particular model assumptions obfuscate interpretation of the
      forecasts are provided. Finally, a brief discussion of how the forecasts were
      used by stakeholders in each state is presented.

PMID- 16886714
TI  - Trends in foreign-trained registered nurses in the United States.

PMID- 16886715
TI  - Characteristics and employment patterns of licensed social workers in the United
      States.

PMID- 16886716
TI  - The impact of the aging population on the health workforce in the United States-
      summary of key findings.

PMID- 16886717
TI  - The United States health workforce profile.

PMID- 16886718
TI  - Lateral osteoarthritis of the knee. Etiology based on morphological, anatomical,
      kinematic and kinetic observations.
AB  - This thesis aimed to study osteoarthritis (OA) of the knee and its subgroup with
      lateral wear (valgus knees). Anatomy, kinematics and kinetics (movements and
      moments) of the hip and knee joint and the sensitivity and specificity of
      diagnostic procedures were evaluated. Our hypothesis was that there are
      biomechanical reasons for development of either lateral or medial OA. The wear
      pattern of the tibial plateau and the femoral condyles was delineated in 42
      patients. The diagnostic accuracy of standing knee radiographs was validated in
      34 and reproducibility and validity of the Ahlback classification was studied in
      48 patients. The Influence of working conditions or gender on the prevalence of
      uni or bilateral knee OA was evaluated in 990 patients from 2 hospitals (Varberg
      and Halmstad) operated during 1985-1994 with knee arthroplasty or proximal tibial
      osteotomy. For each patient, 3 age- and gender-matched controls were found.
      Studies of the anatomy of the hip and pelvic regions and the motions and moments
      in the hip and knee in medial and lateral OA were performed. The detailed
      kinematics of the knee during active extension in lateral OA were recorded using
      dynamic radiostereometry (RSA). In both medial and lateral OA the central part of
      the tibial plateau showed the most pronounced wear (p<0.001), followed by the
      anterior part in medial OA (p=0.02) and the posterior part in lateral OA
      (p=0.001). In medial OA the observed difference between the 2 radiographic
      methods was small and acceptable (median; p=0.05; 0-0.5 mm). In lateral OA there
      was no consistent underestimation, but larger scatter (median; p=0.04; -0.1-1.2
      mm) suggesting less precise determination. The repeatability of the Ahlback
      classification for one observer was fair (kappa: medial OA: 0.15-0.65; lateral
      OA: 0.59-0.76), but between observers it was poor (kappa: 0.1). The validity
      revealed an acceptable sensitivity in both medial (67-95%) and lateral (43--86%)
      OA but the specificity was low (medial: 11-67%; lateral: 25-75%). Farmers (RR:
      1.7; p<0.0005) and building workers (RR: 1.4; p=0.047) run increased risk to
      undergo surgical treatment because of OA of the knee. Unilateral disease was 3.7
      times more common among men. Patients with lateral knee OA had a 14 mm wider
      pelvis (p=0.001) and those with medial knee OA an 11 mm higher offset (p=0.005).
      In the gait analysis they showed more outward rotation of the hip (p=0.001) and
      more inward rotation of the tibia than did patients with medial OA (p=0.001). In
      lateral OA, the medial femoral condyle translated 7-8 mm forward with 450 flexion
      whereas controls translated 4 mm less (p=0.03), without any difference of the
      lateral femoral condyle. Conventional radiographs do not give sufficient
      information for correct grading, especially in lateral OA where the scatter is
      high. The joint space can often be seen on radiographs despite presence of bone
      attrition as observed on the preparations. Increased incidence of unilateral
      disease in men and building workers suggests that this joint disease more
      commonly originates from previous trauma. Our findings suggest that the
      occurrence of medial or lateral OA has a biomechanical background originating
      from pelvis and hip anatomy.

PMID- 16886719
TI  - Characterization and plasticity of the double synapse spines in the barrel cortex
      of the mouse.
AB  - The somatosensory barrel cortex of rodents and its afferent pathway from the
      facial vibrissae is a very useful model for studying neuronal plasticity.
      Dendritic spines are the most labile elements of synaptic circuitry and the most
      likely substrate of experience-dependent alterations in neuronal circuits in
      cerebral cortex. We characterized morphologically and numerically a specific
      population of spines, i.e. double synapse spines, which have two different inputs
      -one excitatory and the other inhibitory, in the B2 barrel of mouse somatosensory
      cortex. We also described changes in morphology of double synapse spines induced
      by classical conditioning in which stimulation of vibrissae was paired with a
      tail shock. The analysis was carried out by means of serial EM micrograph
      reconstruction. We showed that double spines account for about 10% of all
      analyzed spines. The morphology of a typical double synapse spine is similar to
      the morphology of single synapse spine and both consist of two parts--a large
      head and a narrow, long neck. Excitatory synapses are preferentially located on
      the head of double synapse spines and inhibitory synapses are usually located on
      the neck of these spines. The length of the double synapse spine neck decreases
      and the cross-section area of the spine neck increases significantly as a result
      of sensory conditioning.

PMID- 16886720
TI  - Neurons derived from PC12 cells have the potential to develop synapses with
      primary neurons from rat cortex.
AB  - Neuron transplantation is considered to be a promising therapeutic method to
      replace functions lost due to central nervous system (CNS) damage. However,
      little is known about the extent to which implanted neuron-like cells can develop
      into mature neurons and acquire essential properties, and especially formation of
      synapses with host neurons. In this investigation we seeded PC12 cells labeled
      with GFP into primary cultured neurons isolated from rat cerebral cortex to build
      a co-culture system, and then induced the PC12 cells to differentiate into neuron
      like cells with NGF. Seven days later, we observed the relationship between the
      PC12-derived neurons and primary neurons using FM1-43 imaging and immunoelectron
      microscopy, and found that GFP-labeled neurons could form typical synapses with
      host primary neurons. These observations showed that immigrant neurons
      differentiated from PC12 cells could develop into mature neurons and could form
      intercellular contacts with host neurons. Both the immigrant and host neurons
      could construct neuronal networks in vitro.

PMID- 16886721
TI  - Cachexia--induced cerebellar degeneration: involvement of serum TNF and MCP-1 in
      the course of experimental neoplastic disease.
AB  - Cerebellar degeneration may be recognized as a remote effect of a growing tumor.
      We have analysed serum concentrations of tumor necrosis factor-alpha (TNF-alpha),
      macrophage chemoattractant protein-1 (MCP-1), thyroxine and insulin to elucidate
      the pathomechanism which may be of importance for the development of central
      degeneration in cachectic Morris hepatoma bearing rats. Serum TNF-alpha and MCP-1
      levels were evaluated by means of the ELISA system, while thyroxine and insulin
      were estimated by radioimmunoassay. Microscopic examination using hematoxylin
      eosin, Nissl and Kluver-Barrera staining revealed an atrophy in the cerebellum,
      homogenization changes of Purkinje cells and decreased cell density of the
      granular layer. In the Morris hepatoma bearing animals serum MCP-1 content was
      elevated while TNF-alpha, thyroxine and insulin concentrations were decreased.
      This study has demonstrated that circulating TNF-alpha and MCP-1, together with
      decreased levels of insulin and thyroxine accompany and may produce a milieu of
      factors involved in mechanisms of the development of cerebellar degeneration in
      cachectic hepatoma bearing rats.

PMID- 16886722
TI  - Anticonvulsive effects of nimodipine on penicillin-induced epileptiform activity.
AB  - The common features of all types of epilepsy are synchronized and uncontrolled
      discharges of nerve cell assemblies. It is believed that calcium ions play an
      important role in the generation of epileptic activity. Excessive calcium influx
      into neurons is the first step toward a seizure. The aim of the present study is
      to investigate whether the calcium channel blocker nimodipine has anticonvulsive
      effects. The left cerebral cortex was exposed by craniotomy in anaesthetized
      rats. An epileptic focus was produced by injection of penicillin G potassium (500
      units) into the somatomotor cortex. After the epileptiform activity reached
      maximum frequency and amplitude; nimodipine was injected into the same area.
      Application of nimodipine caused an inhibition in the electrocorticograms (ECoG).
      Solvent alone did not affect the epileptiform activity. The results of this study
      indicate that nimodipine may have anticonvulsant effects.

PMID- 16886723
TI  - St john's wort (Hypericum perforatum) counteracts deleterious effects of the
      chronic restraint stress on recall in rats.
AB  - This study aimed at verifying a hypothesis that St. John's wort (Hypericum
      perforatum) alleviates stress-induced memory impairments. Administration of
      Hypericum perforatum (350 mg kg(-1) daily for 21 days) significantly enhanced
      recall of passive avoidance behavior (PAB), but had no effect on the acquisition
      of conditioned avoidance responses (CARs). Rats stressed chronically (2 h daily
      for 21 days) displayed diminished recall of the PAB and this effect was abolished
      by St John's wort. Chronic administration of the "equivalent" to the stress dose
      of exogenous corticosterone (5 mg kg(-1) daily for 21 days) also impaired recall
      of PAB, and this effect was also reversed by Hypericum perforatum. None of our
      treatments produced significant motor coordination impairments as tested in a
      'chimney' test. It appears that H. perforatum prevents stress-induced
      deterioration of memory in rats.

PMID- 16886724
TI  - Effects of risperidone on auditory information processing in neuroleptic-naive
      patients with schizophrenia spectrum disorders.
AB  - Early effects of risperidone (2.5 +/- 1 mg/day) on auditory information
      processing were investigated in 9 neuroleptic naive patients with schizophrenia
      spectrum disorders and 9 healthy controls by using event-related potentials
      (ERPs). ERPs were elicited during active auditory "oddball" paradigm and were
      recorded before and after two weeks of treatment. Baseline P3 latencies were
      significantly delayed in patient group. Risperidone treatment did not change P3
      amplitudes and latencies. However, P2 amplitudes were reduced in parallel with
      the clinical improvement measured by Positive and Negative Syndrome Scale
      (PANSS). Although risperidone did not change neural bases of active attention
      after two weeks of treatment, the reduction of P2 amplitude suggests that
      risperidone may affect auditory information processing in patients with
      schizophrenia spectrum disorders who never have been exposed to antipsychotic
      treatment.

PMID- 16886725
TI  - Topography and axonal collaterals of trigeminocerebellar projection to the
      paramedian lobule and uvula in the rabbit cerebellum.
AB  - To study projections of the trigeminal sensory nuclei (TSN) to the rostral parts
      of the paramedian lobule (PML) and of the uvula of the rabbit cerebellar cortex,
      the retrograde double fluorescent labeling method was used. Injections of Fast
      Blue (FB) into PML and Diamidino Yellow (DY) into the uvula, resulted in
      prominent labeling neurons with FB bilaterally and with DY ipsilaterally, in the
      principal trigeminal nucleus, subnucleus oralis, and rostral and caudal
      subnucleus interpolaris. We observed topographical arrangement of neurons in such
      a fashion that FB labeled cells were localized in the medial and DY labeled cells
      in the lateral regions of TSN. Apart from this small number of double FB+DY
      labeled neurons (n = 138) were found in the narrow common region of single
      labeling. This implies that PML and the uvula receive independent trigeminal
      sensory information from neurons in separate regions of TSN. However, some
      trigeminal neurons may also exert simultaneous influences upon these hemispheral
      and vermal components by way of axonal branchings.

PMID- 16886726
TI  - Mitochondrial DNA in pathogenesis of Alzheimer's and Parkinson's diseases.
AB  - A critical role of mitochondrial dysfunction and oxidative damage has been
      implicated in etiopathology of many neurodegenerative disorders, as well as in
      normal aging. Alzheimer's and Parkinson's diseases are common devastating late
      onset neurodegenerative disorders, associated with mitochondrial DNA variations,
      which are suggested to affect mitochondrial functions. This paper reviews the
      current knowledge on the inherited and somatic mtDNA variations in both
      conditions.

PMID- 16886727
TI  - Nutrition, immunity and the infant and young child.

PMID- 16886728
TI  - Phenylketonuria: management in primary care.

PMID- 16886729
TI  - New thinking about diet and cardiovascular disease.
AB  - The UK has one of the highest CVD rates in Western Europe, with over one-third of
      deaths attributable to this condition. This article looks at how several of the
      risk factors for CVD, including some newly-identified ones, may be reduced by
      dietary interventions. It considers the part played by dietary cholesterol, fats
      and oily fish and summarises practical nutritional advice for health
      professionals to give their clients. The association between nutritional and
      genetic factors is briefly discussed, and the forecast that in the future it may
      be possible to tailor dietary advice on preventing CVD more precisely to the
      individual's particular risk profile.

PMID- 16886730
TI  - Syphilis: still with us, so watch out!
AB  - The number of syphilis cases has been increasing in the UK, partly because of
      localised outbreaks. The sharpest rises have been among men having sex with men,
      but the incidence among heterosexuals has also risen. Blood-test screening for
      syphilis is an important part of sexual health, and includes routine screening of
      pregnant women at the first antenatal visit. Prompt treatment with penicillin in
      the earlier stages can stop the progression of the disease. Unfortunately, public
      awareness of syphilis and its potentially serious consequences is low. It is
      important for health professionals to be alert for signs of the disease and to
      initiate tests if there is a likelihood that a patient has or is at risk for the
      disease.

PMID- 16886731
TI  - Phenylketonuria: practical dietary management.
AB  - Phenylketonuria (PKU) is an autosomal recessively inherited disorder which
      prevents the normal metabolism of protein foods. Phenylalanine builds up in the
      blood and if untreated will cause mental retardation. PKU is treatable by a low
      phenylalanine diet for life. The prognosis is good provided the condition is
      diagnosed within the first two weeks of life and dietary treatment started
      promptly. Special low-phenylalanine formulae and foods are available on
      prescription in the UK. Supervision by a dietitian and regular monitoring of
      phenylalanine levels in the blood are essential. The health visitor and school
      nurse have an important part to play during the school years in supporting the
      family. Midwives also play an important part in ensuring that women with PKU
      adhere to a strict low-phenylalanine diet around the time of conception and
      during pregnancy. They also take blood samples from all newborn babies to be
      tested for PKU.

PMID- 16886732
TI  - "Why does he wheeze?": wheezing and asthma in young children.
AB  - Wheezing is common in young children and parents often worry that the child has
      asthma. The diagnosis of asthma in the under-fives is not always easy but
      assessing the severity of wheezing and whether it is transient, intermittent,
      persistent or associated with viral infection helps health professionals to
      rationalise treatment. This article outlines the different patterns of wheezing
      and some current approaches to management. Although wheezing and asthma are often
      associated, wheezing is commonly due to viral infection and more than 60% of
      children who wheeze during the first three years of life have ceased to do so by
      six years old. Parents of young children with wheeze and/or asthma need support
      and consistent advice from health professionals. Parents who smoke should be
      encouraged and helped to stop, as exposure to tobacco smoke increases the risk of
      a child developing recurrent wheeze, cough and breathlessness.

PMID- 16886733
TI  - Modelling geographically referenced survival data with a cure fraction.
AB  - The emergence of geographical information systems and related softwares nowadays
      enables medical databases to incorporate the geographical information on
      patients, allowing studies in spatial associations. Public health administrators
      and researchers are often interested in detecting variation in survival patterns
      by region or county in order to understand the possible factors that contribute
      towards such spatial discrepancies. These issues have led statisticians to
      develop survival models that account for spatial clustering and variation.
      Additionally, with rapid developments in medical and health sciences, researchers
      increasingly encounter data sets where a substantial portion of patients are
      cured. Models accounting for cure in the population assist in the prognosis of
      potentially terminal diseases. This article proposes a Bayesian modelling
      framework that models spatial associations for areally referenced survival data
      using a general class of cure models proposed by Cooner et al. The special models
      we outline are alternatives to the traditional proportional hazards models and
      can be fitted using standard Bayesian software such as WinBUGS.

PMID- 16886734
TI  - Spatio-temporal point processes, partial likelihood, foot and mouth disease.
AB  - Spatio-temporal point process data arise in many fields of application. An
      intuitively natural way to specify a model for a spatio-temporal point process is
      through its conditional intensity at location x and time t, given the history of
      the process up to time t. Often, this results in an analytically intractable
      likelihood. Likelihood-based inference then relies on Monte Carlo methods which
      are computationally intensive and require careful tuning to each application. A
      partial likelihood alternative is proposed, which is computationally
      straightforward and can be applied routinely. The method is applied to data from
      the 2001 foot and mouth epidemic in the UK, using a previously published model
      for the spatio-temporal spread of the disease.

PMID- 16886735
TI  - Disease mapping in veterinary epidemiology: a Bayesian geostatistical approach.
AB  - Model-based geostatistics and Bayesian approaches are useful in the context of
      veterinary epidemiology when point data have been collected by appropriate study
      design. We take advantage of an example of Epidemiological Surveillance on urban
      settings where a two-stage sampling design with first stage transects is applied
      to study the risk of dog parasite infection in the city of Naples, 2004-2005. We
      specified Bayesian Gaussian spatial exponential models and Bayesian kriging were
      performed to predict the continuous risk surface of parasite infection on the
      study region. We compared the results with those obtained by the application of
      hierarchical Bayesian models on areal data (proportion of positive specimens by
      transect). The models results were consistent with each other and the Bayesian
      geostatistical approach proved to be more accurate in identifying areas at risk
      of zoonotic parasitic diseases. In general, larger risk areas were identified at
      the city border where wild dogs mixed with domestic dogs and human or urban
      barriers were less present.

PMID- 16886736
TI  - Surveillance of individual level disease maps.
AB  - Methods for the production of individual (address) level disease maps are often
      retrospective; they estimate a map of the average relative risk of disease over a
      study period. However, recently, epidemiologists have started to look at weekly
      or monthly reports of disease and assess them for any change in the distribution
      of relative risk. For example, in the United States of America, the Centre for
      Disease Control and Prevention now routinely collects information on over 50
      notifiable diseases every week. In this paper we present a method for the
      detection of a sudden change in the geographical distribution of the disease in a
      prospective study. The method is based on an estimate of the directional
      derivative of the conditional probability of a case, given either a case or
      control has occurred. It is based on standard kernel approaches to nonparametric
      regression and it is readily applied in any standard statistical software
      package. Two simulated examples of sudden clustering around a fixed point are
      provided.

PMID- 16886737
TI  - Methods for detecting disease clustering, with consideration of childhood
      leukaemia.
AB  - In trying to interpret reports of disease clusters in specific localities, it is
      valuable to know whether the disease in question has a general tendency to
      cluster spatially. Methods for investigating localized disease clustering were
      the subject of a comparative study organized by the International Agency for
      Research on Cancer some years ago. This paper addresses some further aspects of
      one of the methods used in this exercise, namely the Potthoff-Whittinghill (P-W)
      test. Particular consideration is given to methodology for estimating the
      magnitude of overdispersion and for detecting whether one area, in particular,
      has an undue influence on the evidence for overdispersion using the P-W test, the
      extent to which is possible to detect clustering over regions of differing sizes
      using a components-of-variance approach and how adjustment for overdispersion
      might affect tests for raised disease rates in specific locations. These points
      are illustrated using data on childhood leukaemia incidence and reference is made
      to other analyses of the geographical distribution of childhood leukaemia that
      are based on this approach.

PMID- 16886738
TI  - Bayesian spatio-temporal analysis of joint patterns of male and female lung
      cancer risks in Yorkshire (UK).
AB  - Recent advances in disease mapping have focused first on including the time
      dimension, thus giving rise to spatio-temporal analysis of the variation of
      disease risk and, secondly, on carrying out joint analysis of two diseases that
      share common environmental risk factors and are, therefore, related. Here, we try
      to combine both issues and present a joint analysis of the spatio-temporal
      variation of the risks of two related diseases processes-male and female lung
      cancer incidence-in a region of England. To do so, we use a Bayesian hierarchical
      model that splits the risk of disease into two spatio-temporal components: a
      shared component and a specific component that calibrates the differential
      between the two diseases.

PMID- 16886739
TI  - [Distribution of HLA class I antigens in patients with uveitis in the presence of
      rheumatic diseases].
AB  - Uveitis associated with rheumatic diseases (RD) is one of the symptoms of an
      autoimmune lesion. A great role in the etiology of the latter is assigned to
      genetic predisposition, HLA antigens in particular. Twenty-four HLA class I
      antigens were histotyped, by applying the Terasaki microlymphocytotoxic test in
      83 patients with uveitis in the presence of different types of RD. All the
      patients and 701 healthy donors making up a control group were Caucasians. The
      results were statistically processed. There was a significant increase in the
      incidence of the antigens of HLA B27 (RR = 10.04; p < 0.01) and A2 (RR = 1.84; p
      < 0.05) and a decrease in that of the antigens of HLA A10, B5, B10, and B13 (p <
      0.05). There was evidence for that there was an association of the antigen of HLA
      B27 with acute anterior uveitis and that of the antigens B 8 and B 35 with
      posterior and generalized uveitis in RD. The specific features of the association
      of antigens and their haplotypes in individual nosological entities of RD are
      presented.

PMID- 16886740
TI  - [Morphometric analysis of the structure of tear and aqueous humor in senile
      cataract].
AB  - The parameters of the wedge dehydrated samples of aqueous humor and tear taken
      from patients with senile cataract were compared by a morphometric assay.
      Computer-aided processing of the images of the test biological fluids was made on
      a Morphotest-1 hardware-software complex. The study has provided evidence for the
      uniformity of distribution of major structural components in the dehydrated
      samples of tear and aqueous humor in each specific examinee. This fact opens up
      possibilities for studying the signs of different intraocular pathological
      conditions from the morphological pattern of tear.

PMID- 16886742
TI  - [Standardization of color images of the fundus of the eye].
AB  - The development of the programs analyzing the image of the fundus of the eye has
      aroused considerable interest in computer-aided diagnostic tools. At present the
      majority of such programs is based mainly on the analysis of information of the
      brightness and color of an image. The paper proposes a procedure for correcting
      the color images of the fundus of the eye, by lowering the impact of color
      differences caused by external causes, such as the spectrum of a light source,
      the spectral characteristics of ocular optical medium transmission, and those of
      a photo receiver. The procedure for correcting the color retinal images is to
      standardize the color of an image and makes it possible to use information on
      color with more confidence to recognize diseases of the eye grounds and the
      natural course of a pathological process.

PMID- 16886741
TI  - [Pharmacokinetics of radiotracers in the ocular tissues exposed to infrasound and
      ultrasound phonophoreses].
AB  - The paper compares the efficiency of infrasound and ultrasound phonophoreses. The
      efficiency was evaluated on the basis of the rate of radiotracers within the eye
      after infrasound or ultrasound exposure of the eyeball. The exposure was made
      after preliminary putting the radiotracer-impregnated application into the bulbar
      conjunctiva of an animal. Radioactivity was recorded on a Siemens gamma camera in
      its lifetime. The time course of changes in the radioactivities measured 10, 30,
      and 60 minutes after termination of exposures strongly suggests its stable
      increase in the eye exposed to infrasound. At the same time 10 minutes after
      ultrasound exposure, the increased concentration of a radiotracer in the eye was
      less than that after infrasound exposure and then it progressively decreased.
      Thus, having a significant phoretic activity, infrasound, as ultrasound, creates
      more favorable conditions for long drug storage in the eye.

PMID- 16886743
TI  - [Childhood ophthalmoplasty].
AB  - The paper lays down the basic principles of ophthalmoplastic treatment on the
      basis of an analysis of the results of treatment and follow-ups of 2300 patients
      aged 6 months to 18 years who have abnormalities of the orbit and appendages of
      the eye. Emphasis is laid on the preference of methods for plastic repair, using
      local tissues, and free autologous grafting of the skin and mucosa. A soft
      material that is to be easy grown through, such as Carbotextim-carbonic felt, is
      recommended when contour plastic repair of the orbit is required. For hanging, a
      mersilene mesh should be employed in case of blepharoptosis. To achieve the
      better cosmetic results, it is better to operate at the age of more than 4 years;
      however, treatment should be initiated at the age of 1 year when there are
      available functional indications (symblepharon, ablepharia, or cryptophthalmus).

PMID- 16886744
TI  - [Implantation of porous polytetrafluoroethylene orbital inserts: techniques and
      outcomes. Communication 1].
AB  - This paper presents the outcomes of 230 primary, advanced, and secondary implants
      of polytetrafluoroethylene orbital inserts manufactured by the closed joint stock
      company "Nauchno-Proizvodstvennyi Kompleks (Scientific-and-Production Complex)
      "Ekoflon" (Saint Petersburg). The duration of a follow-up was 6-36 months (mean
      15.9 +/- 037 months). The accumulated experience suggests that
      polytetrafluoroethylene orbital inserts are noted for their biocompatibility,
      easiness of manual treatment, and simplicity of implantation. Thus, porous
      polytetrafluoroethylene orbital inserts are promising medical articles designed
      for the prevention and treatment of the anophthalmic syndrome.

PMID- 16886746
TI  - [Prevention of myopia in children].
AB  - Eye diseases rank third in the structure of morbidity among children aged 0 to 17
      years. Acquired myopathy is the leading abnormality in the structure of
      morbidity, with diminished vision being in 28% of preschool children and in every
      two school graduates. Myopia is attended by the signs of systemic connective
      tissue dysplasia and impaired circulation due to autonomic dysfunction. Early
      diagnosis and correction of autonomic dysfunction is the basic line of the
      prevention and treatment of school myopia. Treatment of children can be organized
      in the medical room of a school. Along with general health-improving measures,
      physiotherapetic procedures, such as lens exercises, curative gymnastics,
      massage, and gentle manual therapy procedures should be used in the multimodality
      treatment of children with myopia. Autonomic tone can be regulated through the
      visual analyzer by pulse photostimulation on a spectral ophthalmologic apparatus
      (an up-to-date ACO-05 software model ("DEST", Cheboksary). Moreover, circulation
      improves, eye muscles become stronger, visual reflexes restore, and vision
      improves. A school oculist's room may be used as a new health-improving form in
      children with myopia. It should be set up in every school since the high
      efficiency of treatment for accommodation spasm is an important argument of the
      prevention of myopia, promotes a greater coverage of children with early myopia
      by means of therapeutic measures, as well as timely and contemporary prevention
      of progressive myopathy.

PMID- 16886745
TI  - [Implantation of porous polytetrafluoroethylene orbital inserts: complications.
      Communication 2].
AB  - The purpose of the study was to analyze the pattern and frequency of
      complications following 230 implants of porous polytetrafluoroethylene (PTFE)
      orbital inserts. The total frequency of the complications to be treated was 7.4%.
      Among them there were pointed conjunctival perforations during enucleation
      (1.3%); early exposures of orbital inserts due to surgical defects (2%); late
      exposures caused by the planned replacement of an old prosthesis by a new one
      that had proved to be poorly adjusted (1.4%); significant bleapharoptosis (2%);
      lower eyelid atony (0.7%). Noteworthy is the fact that there were no infectious
      complications. Thus, implantation of PTFE orbital inserts is attended by a very
      narrow range of the complications, which are typical of this branch of
      ophthalmosurgery, whose frequency is not greater than the use of implants made
      from other porous materials.

PMID- 16886747
TI  - [Outcomes of secondary implantation of posterior-chamber intraocular lenses in
      children with capsular and scleral sutural fixation].
AB  - The functional results and postoperative complications of secondary implantation
      of posterior-chamber artificial lenses (AL) in 122 children (165 eyes) aged 2 to
      7 years. The specific feature of this operation in children is the high frequency
      of postoperative complications: 48 and 60% after capsular fixation and scleral
      sutural fixation, respectively. In most cases, they appear as a second-grade
      inflammatory reaction in the early postoperative period and as slowly progressive
      iridocyclitis in the late postoperative period. Secondary implantation of
      posterior-camber ALs with capsular fixation is an effective and safe technique
      for correcting aphakia in children, by yielding good functional results.
      Postoperative complications are treatable and fail to lower visual acuity.
      Secondary implantation of ALs with scleral fixation in children is associated
      with a relatively high risk of intractable complications that decrease visual
      results and it should be performed in single cases if there are strict
      indications.

PMID- 16886748
TI  - [Laser thermokeratoplasty in the treatment of hyperopia in children].
AB  - The effectiveness, safety, and stability of multimodality treatment for
      hyperopia, hyperopic and mixed astigmatism complicated by amblyopia and
      anisometropia were studied in 117 patients (117 eyes) aged 9 to 16 years, by
      using the new laser units "Lik-100" and "Glasser" at 1.54 microm. The patients
      were divided into 3 groups: 1) 43 patients (43 eyes) with hyperopia, spheric
      anisometropia and amblyopia; 2) 38 patients (38 eyes) with hyperopia, simple and
      complicated hyperopic astigmatism, astigmatic anisometropia, and amblyopia; 3) 36
      patients (36 eyes) with hyperopia, simple and complicated hyperopic astigmatism,
      mixed anisometropia, and amblyopia. All the groups underwent multimodality
      treatment involving laser thermokeratoplasty and drug therapy for amblyopia. In
      children and adolescents, the refraction effect was 2.99 and 3.61 (mean 3.37 +/-
      0.60) diopters, respectively. Astigmatism diminished by 2.01 diopters (63%) in
      children and by 2.62 diopters (79%) in adolescents (mean 2/35 diopters). The
      predictability of a refraction effect in the range of +/- 0.5 diopters averaged
      77% in all the groups. Anisometropia diminished by an average of 2.88 +/- 0.8
      diopters, which was 85% of the baseline data (the upper range of residual
      refraction was not more than 1.5 diopters. In all the groups, uncorrectable
      visual acuity increased by an average of 0.36 diopters (0.43 and 0.4 diopters in
      children and adolescents, respectively); correctable visual acuity increased by
      an average of 0.22 diopters (0.36 and 0.31 diopters in children and adolescents,
      respectively). Loss of correctable visual acuity lines did not greater than 2.7%
      (5 eyes). That of endothelial cells was not more than 6-8%. The angle of squint
      strabismus could be decreased or corrected in 79% after treatment. Binocular
      vision restored in 57%.

PMID- 16886749
TI  - [Correction of lagophthalmos after esthetic blepharoplasty with soft contact
      lenses].

PMID- 16886750
TI  - [Use of pterygopalatine ganglionic block in the treatment of malignant glaucoma].

PMID- 16886751
TI  - [Problems in the formation of a locomotor stump during eyeball removal].

PMID- 16886752
TI  - [Immunomodulation of injury and stress-induced immunological disorders in
      penetrating wound of the eye].

PMID- 16886753
TI  - [Embryonic development of retinal vessels in health].

PMID- 16886754
TI  - [Oral or trandsdermanl hormone replacement therapy reduces interleukine-6
      levels].
AB  - OBJECTIVE: To compare the effect of oral and transdermal estrogen replacement
      therapy (ET) on circulating interleukin-6 (IL-6) in post-menopausal women.
      PATIENTS AND METHOD: Prospective open trial study in 55 healthy hysterectomized
      postmenopausal women with a mean age of 52 years. Twenty-seven women received
      oral conjugated equine estrogens (0.625 mg daily) and the remaining 28 received
      transdermal estrogen replacement therapy (50 microg/day) during 6 months. At
      baseline both groups were similar as to age, body weight, and body mass index as
      well as serum levels of LH, FSH, 17-beta estradiol (E2) and IL-6. RESULTS:
      Baseline elevated IL-6 levels decreased significantly (p<0.05) after both oral
      and transdermal estrogen replacement therapy; this decrement showed no difference
      between the two groups. After the follow-up there were no differences in body
      weight and body mass index between groups; however, in the oral group there was a
      trend to increment this parameters. Serum levels of E2 and IL-6 were negatively
      correlated in the two groups and IL-6 was positively correlated with body mass
      index in untreated women and this correlation was the same in women with estrogen
      replacement therapy. CONCLUSIONS: The decrement of IL-6 after estrogen
      replacement therapy was similar for both routes of administration; in addition IL
      6 had a negative correlation with E2 and a positive correlation with body mass
      index.

PMID- 16886755
TI  - [High prevalence of group B Streptococcus colonization in Mexican pregnant
      women].
AB  - OBJECTIVE: To determine the prevalence of group B Streptococcus (GBS)
      colonization in two anatomical sites in Mexican women of childbearing age, as
      well as the associated risk factors. PATIENTS AND METHOD: A retrospective cohort
      analysis was made with two groups of women between 14 and 44 years old. We formed
      two groups of 72 women; one had a recent positive group B Streptococcus culture
      and the other, paired by age and culture date, had a negative culture of the same
      bacterium. All of them answered a validated questionnaire and two rectal swabs
      were obtained and cultured for isolation of group B Streptococcus. RESULTS:
      Prevalence of GBS colonization was 18% for two anatomical sites (heavy
      colonization), and 37% for one anatomical site; the overall prevalence was 54.9%.
      Three or more sexual partners increased by 4-fold the risk of heavy GBS
      colonization (p < 0.01). In this study 49 (34%) women were pregnant, 26 (53%) of
      them were colonized by GBS and 7 (14.3%) were heavy colonized. CONCLUSIONS:
      Prevalence of GBS during pregnancy in Mexican women was higher than the reported
      previously, even in developed countries. Risk of colonization increased by 4-fold
      with a history of three or more sexual partners.

PMID- 16886756
TI  - [Intrauterine growth in a selected group of Peruvian twins].
AB  - BACKGROUND: Newborn twins have high risk of morbidity and mortality. They are
      classified with intrauterine growth curves of unique fetuses; they do not exist
      Peruvian curves for this group. OBJECTIVE: To know the intrauterine growth of a
      selected group of Peruvian twins and compare it with patterns of unique newborns.
      PATIENTS AND METHOD: In a descriptive, transversal and prospective study made
      during 13 years (1992-2004) at the Hospital Hipolito Unanue of Tacna-Peru we
      selected 282 twins (54%) without factors that alter the intrauterine growth. We
      obtained averages, standard deviation and percentiles 10, 50 and 90 of weight,
      height, and cephalic perimeter for gestational age of 32 to 41 weeks, which were
      corrected with a second-order polynomial. We compared the values of the
      percentiles and the averages with the unique newborns curves. The value of p <
      0.05 was considered significant. RESULTS: From 36,909 newborns alive, 518 were
      twins, and of those we selected 282. The most representative group was formed by
      those who were in the week 38, in which percentiles 10 and 90 of weight were
      2,275 and 3,180 g, of size 45.8 and 48.4 cm, and of cephalic perimeter 323 and
      354 mm, respectively. Comparing the twins with the unique newborns at week 38,
      the difference of weight in percentile 50 was 452 g. Regarding the somatometric
      parameters, weight was the most affected, 44.3% of the twins were under
      percentile 10 of the curve of weight for unique newborns; followed by height with
      22.3% and cephalic perimeter with 5%. When comparing the intrauterine growth for
      weight of twins with unique newborns the performance was similar until week 34,
      from which growth had a significant deterioration. When classifying the newborn
      twins we found a frequency of 12.3%, which increases to 37% with the curves of
      unique newborns. CONCLUSION: The twin intrauterine growth curves differ
      significantly from the unique newborns growth. It is recommended to use specific
      charts for twins in order to evaluate their intrauterine growth appropriately.

PMID- 16886757
TI  - [Heart disease and pregnancy].
AB  - This report is about one of the main frequent causes of mother mortality, with
      the main purpose of creating conscience and alerting to medical population about
      the importance of the adequate and opportune cardiology and obstetric diagnosis
      and treatment. Also refers the main hemodynamic changes in pregnant woman, the
      risk of death according to the specific suffering, and the obstetric and
      cardiological control parameters; trying to diminish as much as possible the
      perinatal and mother mortality.

PMID- 16886758
TI  - [Ofuji's diseases and pregnancy. A report of a case].
AB  - Eosinophilic pustular folliculitis, which was first described by Ofuji, is a type
      of dermatosis characterized by pruritic, follicular, papules and pustules that
      gradually extend peripherally and have central tendency. Ofuji's disease has been
      rarely reported, and has not been reported in pregnancy. It's possible that
      hypersensitivity reaction plays an important role. There is no consensus on
      treatment approaches. We present the case of a 27 year-old woman during the 12.5
      weeks of her first pregnancy; she had developed Ofuji's disease for 17 years.
      Previously, she had been treated with corticosteroid and azatioprine for 15
      years, which were suspended by the time she was diagnosed with pregnancy. Then,
      she was referred to our maternal fetal medicine department, and was treated with
      prednisone 25 mg a day. The patient had urinary infection and vulvovaginitis at
      the week 14.2, with peripheral blood eosinophilia. She had exacerbations at the
      weeks 35.2 and 38.1, which were treated only with prednisone and topical
      management; furthermore she had a total of 4 kg of weight gain during the whole
      pregnancy. Cesarean delivery was performed for nonreassuring fetal heart rate.
      Perinatal results were: woman with lower birth weight: 2,450 g, Apgar 5.8,
      placenta with calcifications on 60% of it and single nuchal cord. She had
      exacerbations in late puerperium. A healthy newborn was obtained and no clinical
      findings of dermatoses were found. Maternal autoimmune diseases may induce
      remission or exacerbation during pregnancy. Nevertheless, in this case the
      induced exacerbations during puerperium and the fact that a low birth weight was
      obtained are problems commonly associated with the prolonged use of
      corticosteroids during pregnancy.

PMID- 16886759
TI  - [Fatty liver in pregnancy. A report of two cases and medical literature review].
AB  - Acute fatty liver of pregnancy is an uncommon and potentially fatal disorder
      usually found in the third trimester of pregnancy and the early days postpartum.
      It is characterized by a micro vesicular stheatosis of the liver, which is
      reversible with complete regression of the disease. We present two clinical
      cases, in the first one the patient developed encephalopathy and hypoglycemia in
      her third day post cesarean section; the patient underwent surgical exploration
      because of a subaponeurotic hematoma and the diagnosis was confirmed by liver
      biopsy. The patient presented spontaneous resolution of the disease and was
      discharged home on her 21st day after delivery. The second case was a patient on
      her 37th week of pregnancy that arrived to the emergency room complaining of
      malaise, nausea and vomit, her laboratory analyses were remarkable hypoglycemia
      and hyperbilirubinemia. She underwent elective pregnancy termination with a
      favorable maternal and fetal outcome towards spontaneous resolution. It is
      critical to diagnose and treat this disease in a expedite manner in order to have
      a favorable maternal and fetal outcome. The mortality rate has decreased
      dramatically from 80% in 1965 to 100% survival in 1999 according to the latest
      reviews. This regression of the symptoms and signs along with normalization of
      the laboratory values has driven some authors to call this disease as the
      "reversible peripartum liver failure".

PMID- 16886760
TI  - [Hypertriglyceridemic pancreatitis during pregnancy. A report of a case].
AB  - Acute pancreatitis during pregnancy is an uncommon complication. The usual cause
      is biliary tract disease. Cholesterol and triglyceride plasma levels
      physiologically increase during pregnancy. Pregravidic hypertriglyceridemia (as
      much primary as secondary) may be exacerbated and occasionally act as the
      trigger. Early diagnosis and treatment are the keys because related morbidity and
      mortality are high. We report a case of diabetic ketoacidosis and
      hypertriglyceridemia-induced gestational pancreatitis (tryglicerid level of
      12,100 mg/dL) treated successfully with conservative management. The clinical,
      biochemical and therapeutic aspects comment in addition of this pathology, as
      well as its prevention

PMID- 16886761
TI  - [Contribution of Dr. Arturo Zarate to gynecology and obstetrics in Mexico].

PMID- 16886763
TI  - [Diabetes].

PMID- 16886762
TI  - [Surgical consequences that can complicate pregnancy or labor evolution. 1951].

PMID- 16886764
TI  - [Pregnant diabetic patients: institutional experience].
AB  - BACKGROUND: Diabetes mellitus complicates 3-5% of all pregnancies and is a major
      cause of perinatal morbidity and mortality. The diet and insulin have
      revolutionized the care related with pregnancy complicated by diabetes mellitus.
      OBJECTIVE: To report the management experience in patients with diabetes and
      pregnancy at the Instituto Materno Infantil, Estado de Mexico. PATIENTS AND
      METHOD: A descriptive, retrospective, observational and cross-sectional study of
      pregnant women with diabetes and pregnancy was conducted from 2003 to 2004.
      RESULTS: We included 55 pregnant women who had: gestational diabetes 30 (54.4%),
      pregestational diabetes 24 (43.6%), and carbohydrate intolerance 1 (1.8%); every
      one of them were controlled either with diet, insulin or both. The mean age was
      30.6, 80% with family history of type 2 diabetes mellitus, 9% gestational
      diabetes. Gestational diabetes was diagnosed in 33.3% by abnormal 50 g glucose
      screening and 46.6% with oral glucose tolerance test (OGTT). The main
      complications among the patients were urinary disease (61.3%) and the major fetal
      malformation were those related with cardiovascular disease (9.09%). The most
      frequent mode of delivery was cesarean section (58%) and birth weight was of
      3,146 g. CONCLUSIONS: The main risk factors identified among women in the study
      group were as follow: More than 25 years of age and family history of diabetes
      mellitus. We observed a progressive increase in the insulin dosage. The most
      consistent complications among the patients were urinary infection and the major
      fetal malformation was cardiovascular disease.

PMID- 16886765
TI  - [Functional changes in urethra secondary to partum vs cesarean section. Evidence
      with dynamic perfilometry].
AB  - BACKGROUND: The vaginal delivery produces anatomic and functional disease in the
      pelvic floor. The urethral profilometry, part of urodynamic study, represents
      graphically the urethral functionality. OBJECTIVE: To determine the functional
      changes in the dynamic profilometry in women with antecedent of vaginal delivery
      or cesarean section. PATIENTS AND METHOD: This is a correlation transversal study
      of 310 urodynamic studies in the Uroginecology Coordination, National Institute
      of Perinatology at 2003. RESULTS: We found a statistically significant
      correlation between vaginal delivery and urethral close area and the continence
      area, determining that a higher number of vaginal deliveries is associated with
      lower urethral close area and lower continence area.

PMID- 16886766
TI  - [Gestational diabetes. Diagnosis in early stages of the pregnancy].
AB  - OBJECTIVE: To determine whether women with early diagnosis of gestational
      diabetes have an increase of the rate of gestational hypertensive disease,
      metabolic imbalance, higher insulin dosage requirement, perinatal morbidity and
      perinatal death than those in whom diabetes developed after 24th week. METHODS:
      All pregnant women with gestational diabetes were studied. Maternal age,
      pregestational body mass indexes, total weight gain during pregnancy, gestational
      age at diagnosis, and the timing of delivery were recorded. Two groups were
      studied: women with gestational diabetes diagnosed before 24 gestation weeks and
      those in which diabetes was diagnosed at 24 weeks or later. Total insulin dosage,
      rate of gestational hypertension, perinatal morbidity, perinatal death, and
      percentages of women with good metabolic control were analysed. RESULTS: In the
      whole group 28% were diagnosed before 24 weeks of gestation. Women that were
      diagnosed earlier had grater pregestational body mass indexes (30 +/- 6 kg/m2 vs
      27 +/- 6 kg/m2) and total weight gain during pregnancy was lower during over all
      gestation (8 +/- 5 kg vs 10 +/- 6 kg). Insulin requirements were higher in women
      diagnosed earlier and there were no differences in the rates of gestational
      hypertension, and perinatal death. Perinatal morbidity was significantly higher
      in patients who were diagnosed later CONCLUSIONS: Early diagnosed and treatment
      may result in decreased perinatal morbidity. Women with early diagnosed diabetes
      required higher insulin dose, but they did not represent a high risk subgroup.

PMID- 16886767
TI  - [Elaboration and validation of an index for preeclampsia diagnosis].
AB  - OBJECTIVE: To build a consistent and valid preeclampsia diagnosis index (IDP) for
      its Spanish acronyms. PATIENTS AND METHOD: The study was done in a Gyneco
      Obstetrics Hospital and a Family Medicine Unit from March 2000 to February 2001.
      Fifty items were chosen from the literature, with a design to validate diagnostic
      tests, which were assessed by family doctors and gyneco-obstetricians in regard
      to their appearance and content validity. Concurrent criterion validity. Golden
      standard: Two gyneco-obstetricians diagnosed pre-eclampsia (hypertension and
      proteinuria). Simultaneously a family doctor (in an independent and blinded way)
      questioned, examined and recorded laboratory data of 219 preeclamptic patients
      and 251 non preeclamptic patients. RESULTS: Preeclampsia diagnosis index is an
      additive index with 21 clinical and paraclinical parameters weighted according to
      their individual diagnostic capacity. It has two parts: The first one with 82%
      (95%CI 80-84) sensitivity; 93% (95%CI 91-95) specificity; the second one with 86%
      (95%CI 83-89) sensitivity; 75% (95%CI 65-85) specificity. CONCLUSIONS:
      Preeclampsia diagnosis index is easily applied and has immediate results, which
      makes easier the physician's decisions.

PMID- 16886768
TI  - [Origin of neonatal morbidity].
AB  - OBJECTIVE: To identify the different diseases that have an influence on neonatal
      morbidity, with the purpose of suggesting rules that prevent and avoid it.
      PATIENTS AND METHOD: We made a clinical study of the mothers and new-born babies
      that were admitted at the Tocosurgery and Neonatology Department for presenting a
      disease that requires its treatment and follow-up in such department. The study
      was retrospective, transversal, descriptive and observational, and it was made
      from January 1st to April 30th 1999 at the Hospital General de Zona numero 1,
      IMSS. RESULTS: The morbidity was of 20% and it was more frequent in the masculine
      gender (53%) and in babies with 2,500 to 3,000 g (60%). Among the most common
      diseases we found: respiratory difficulty (10%), macrosomia (15%), early membrane
      rupture (12%), hypotrophy (11%), and children of mothers with Rh negative blood
      (10%). CONCLUSIONS: The analysis of the morbidity obligues to identify, through
      the identification of the risk factors during pregnancy, labor and delivery, the
      patients in high risk in order to prevent and avoid neonatal morbidity, as well
      as to obtain better results in the new-born.

PMID- 16886769
TI  - [Physiopathology and nutritional care of patients with gestational diabetes].
AB  - Maternal risks include the development of diabetes after pregnancy, as well as
      having an infant with macrosomia, with elevated risk of developing obesity and
      diabetes in childhood. The main goal of treatment is to maintain an adequate
      glycemic control during pregnancy and guarantee the recommended weight gain. The
      first treatment strategy is diet therapy, however, some women need insulin
      therapy to achieve adequate glycemic control. The risk of diabetic fetopathy
      decreases when maintaining postprandial glycemic levels within normal ranges.
      These levels are directly associated with the amount and type of carbohydrates
      consumed during meals. So, nutrition therapy should be an integral part of
      gestational diabetes treatment. Nutrition therapy includes a complete nutrition
      assessment, an individual food plan that meets energy and protein requirements
      for pregnancy (in obese women never lesser than 1,700 kcal/day), in which lipids
      and carbohydrates may provide lesser than 40 and between 40 and 45% of total
      energy intake. Education about food groups that provide carbohydrates, portion
      sizes and how to achieve an equal carbohydrate distribution throughout the day
      should be provided. Orientation about eating healthy fats and increasing the
      consumption of high-fiber foods should also be included. This approach requires
      that treatment of women with gestational diabetes should be provided by a
      multidisciplinary team, including nutrition specialists.

PMID- 16886770
TI  - [Spontaneous hepatic rupture of pregnancy. A report of four cases and medical
      literature review].
AB  - The spontaneous liver rupture associated with preeclampsia is a potential life
      threatening condition that requires a multidisciplinary team approach. There are
      near 200 cases reported in the world literature. This paper presents four cases
      of liver rupture associated with preeclampsia, three of which were consecutive
      with only two days apart, describing the clinical features and the therapeutic
      approaches. We also discussed about the mortality, which occurred in one of our
      cases, and perinatal mortality that affected one newborn and another one had
      neonatal encephalopathy secuelae. Three of the cases were managed in a surgical
      manner, one of them also with selective hepatic artery embolization meanwhile
      another one received conservative management. It is important to suspect this
      pathology in the preeclamptic patient, especially if she develops HELLP syndrome,
      in order to establish opportune diagnosis and treatment with a team including the
      intensive care, surgery and obstetrical staff.

PMID- 16886771
TI  - [Advances of obstetrics in Mexico in the last 50 years. 1951].

PMID- 16886772
TI  - [Microsporidiosis: an emerging and opportunistic infection].
AB  - Microsporidiosis is considered as an emerging and opportunistic infection. The
      etiologic agents, microsporidia, are small single-celled and obligate
      intracellular organisms. Recently they were reclassified with the fungi. Of the
      14 species currently known to infect humans, Enterocytozoon bieneusi and
      Encephalitozoon intestinalis are the most common. Species infecting humans have
      been found in wild, domestic, and food-producing farm animals, as well as in
      water sources, raising concerns for zoonotic, foodborne, and waterborne
      transmission. Chronic or self-limiting diarrhea is the most common symptom
      associated with microsporidiosis in immune-suppressed or immune-competent
      individuals. In patients with human immunodeficiency virus (HIV) infection rates
      up to 50% have been reported. In Venezuela, the extent of microsporidial
      infection and its effects on human health are unknown. In a recent study of 103
      HIV-infected patients from ten different sectors of Zulia State, microsporidian
      infections were identified in 14 (13.6%) of them; this finding suggests that
      microsporidia are common among these patients and are widely distributed in the
      region. Therefore, it is necessary to implement the techniques to diagnose these
      infectious agents in the health laboratories in the country in order to prescribe
      the specific treatment and to study the risk factors for infection to develop
      preventive measures to control the spread of microsporidia.

PMID- 16886773
TI  - [Isolation of Helicobacter pylori in gastric mucosa, dental plaque and saliva in
      a population from the Venezuelan Andes].
AB  - Helicobacter pylori infection is common in people. However, the existence of
      extra gastric reservoirs and transmission routes remain controversial in the
      field. Because the oral cavity has been proposed as a reservoir for H. pylori, a
      study was carried out to determine the presence of H. pylori in dental plaque and
      saliva. The results were asociated with those obtained in the gastric biopsy.
      Ninety-seven dyspeptic and fifty asymptomatic patients were studied and samples
      taken for biopsy, dental plaque and saliva. The gastric biopsies were evaluated
      using microbiology and histology methods. Cultures and urease tests were carried
      out on the oral cavity samples and included pretreatment methods using urea and
      HCl. The frequency of H. pylori for all the patients evaluated was 75.5%. H.
      pylori was not isolated in saliva or dental plaque in any of the two groups
      studied with or without sample pretreatment. The urease test in dental plaque was
      positive in 99.3% of the patients and 89.8% in saliva. There was no statistically
      significant difference between the infection prevalence by H. pylori in dyspeptic
      or not dyspeptic patients. The obtained results suggest that the methodology used
      for the detection of H. pylori is not sufficiently sensitive for the
      determination of the microorganism in the oral cavity.

PMID- 16886774
TI  - [Prevalence and characterization of hearing loss in workers exposed to industrial
      noise of the turbogenerated electric plant of a petrochemical industry].
AB  - The purpose of the present study was to assess the impact of occupational
      exposure to noise and its relationship with other factors that can induce hearing
      loss in the electric plant workers of a petrochemical industry of the west of
      Venezuela. A cross-sectional study was conducted that included sonometry tests,
      carried out according to the established methodology by COVENIN rules, and the
      occupational medical evaluation and liminal tonal audiometrics test in 75
      workers. The equivalent noise levels (Leq) was quantified in different
      workplaces. It was found out that most of the workers are exposed to high noise
      levels [>85 dB(A)] and during more time than the recommended. All workers use
      hearing protectors appropriately. The hearing loss prevalence in workers was
      16.0%, there were not noise-induced hearing losses. The hearing threshold
      registered in the audiometrics test was diminished, but inside the normal
      threshold values. We diagnosed 12 cases of conductive hearing loss, all grade I;
      there were not sensorial or mixed hearing losses. There was not a relationship
      between the equivalent noise level and hearing loss. It is suggested the design
      and implantation of a program of auditory conservation to protect the health and
      security of the workers and to conduct a longitudinal study considering the
      findings of the present study as it basis.

PMID- 16886775
TI  - Cardiovascular excitatory effect on rats of a fraction isolated from the eyestalk
      of shrimp: Peneaus vanameii.
AB  - The crustacean nervous system is an important source of substances with diverse
      biological activities, particularly affecting invertebrate cardiocirculatory
      physiology. However, the effects of these substances on the cardiovascular system
      of higher vertebrates are not very well documented. The purpose of this study was
      to evaluate the effects of a cardioexcitatory substance (CES) isolated from the
      eyestalk of the shrimp Peneaus vanameii on rat cardiovascular function. The
      administration of a purified fraction of this substance raised mean arterial
      pressure by 37.33 +/- 5.00 mm Hg, pulse pressure 35.00 +/- 4.93 mm Hg and heart
      rate 80.00 +/- 12.83 beats/min over basal values (p < 0.01). Evaluation of the
      possible underlying mechanisms of this hypertensive and tachycardic effect
      reveled that dihydroergotamine pretreatment (20 microg/0.2 mL) reduced the effect
      of CES on mean blood pressure, but not on heart rate. Propranolol pretreatment (4
      microg/0.2 mL) reduced the tachycardia, but not the hypertensive response.
      Enalapril pretreatment (5 microg/0.2 mL) did not modify the effects induced by
      CES on heart rate or blood pressure, and the verapamil pretreatment (1 microg/0.2
      mL) reduced both cardiovascular changes by 85% (p < 0.01). These results indicate
      that CES isolated from the shrimp eyestalk produces hypertension and tachycardia
      mediated by adrenergic receptors in association to calcium channels activation.

PMID- 16886776
TI  - [Anthropometric characteristics and skeletal maturity of male Venezuelan
      swimmers].
AB  - Knowledge of the morph-physiological conditions of young athletes, it of the
      utmost importance for planning better trainning programs and to identify those
      characteristics that lead to a better performance. This paper aims to classify a
      group of 114 male Venezuelan swimmers of the Miranda State contingent, aged
      between 7.00 and 18.99 years old, based on their anthropometric characteristics
      and skeletal maturity. For this purpose multivariate methods: Analysis of
      Principal Components (APC) and the Automatic Classification were employed.
      Anthropometric variables followed the International Society for the Advancement
      of Kinantropometry (ISAK) guidelines. Skeletal maturity and five indexes of body
      composition: brachial, crural, cormic and acromiale-iliac indexes, were
      additionally considered in the analysis. Three groups emerged very well defined
      and homogenous within and between groups. The first group identifies the younger
      swimmers with the smallest values in corporal dimensions. The second group
      comprises those swimmers characterized fundamentally by a greater development of
      the bicrestal diameter. In the third group, greater values of the
      anthropometrical variables were found, that shaped the typical profile of the
      swimmers, mainly characterized by a trapezoidal trunk. Most of the swimmers are
      advanced in skeletal age related to chronological age. This clustering of the
      swimmers permits a suitable way to identify the bio-morphological characteristics
      of the athletes.

PMID- 16886777
TI  - [Insulin sensitivity and beta cell function in different glucose tolerance
      status].
AB  - The objective of this work was to investigate the insulin sensitivity (SI) and
      the beta cell function (BCF) in different glucose tolerance statuses in a
      comparative cross-sectional study. Eighty-four patients with different glucose
      tolerance statues were classified as normoglicemic-control group (NC) patients
      without family history of type 2 diabetes (DM2) or hypertension (HTN);
      normoglicemic-patients with familiar history of DM2 or HTN (FPDM2); patients with
      glucose intolerance (IGT group) and patients with diagnostic of DM2 <10 years
      (DM2 group). In each patient was obtained a clinical history and an oral glucose
      tolerance test (75 g) was performed. Glucose (GOD-PAP) and insulin (RIA) were
      quantified. Insulin Sensitivity (IS) (Whole Body Insulin Sensitivity Index),
      Insulin resistance (IR) (HOMA) and BCF (insulinogenic index) were evaluated. The
      statistical analysis was realized in SPSS v. 10.0. It was found that glucose was
      similar among NC, FPDM2 and IGT groups. Insulin was higher in the FPDM2 (26.71 +/
      22.25 microU/mL), and IGT (34.10 +/- 34.98 microU/mL) in comparison with NC
      (22.83 +/- 21.26 microU/mL) (p < 0.01). IS was different among NC and IGT group
      (0.74 +/- 0.43 to 0.29 +/- 0.18, p < 0.05) and among IGT and DM2 (0.29 +/- 0.18
      to 0.86 +/- 0.55, p < 0.001). BCF was different among the DM2 and NC (0.051 +/-
      0.05 to 1.28 +/- 1.99 microU.mL/mg.dL, p < 0.05), DM2 and FPDM2 group (0.051 +/-
      0.05 to 1.23 +/- 1.51 microU.mL/mg.dL, p < 0.01), DM2 and IGT (0.051 +/- 0.05 to
      2.64 +/- 2.22 microU.mL/mg.dL, p < 0.001). SI was inversely related to corporal
      weight and IMC (r = -0.38, p = 0.001 and r = -0.33, p = 0.004, respectively). BCF
      was related to age (r = -0.27, p = 0.016), the area under curve of glucose (r = 
      0.30, p = 0.010) and body weight (r = 0.34, p = 0.002). In conclusion, the
      decrease of glucose tolerance was associated with the lowering of Insulin
      Sensitivity (IS). The beta cell function (FCB) was lower in the diabetic patients
      group in comparison with the TGA and FPDM2 groups. These measurements need to be
      included in patients with high risk for early identification and changes in life
      style to protect the normal functioning of beta cell and to prevent the onset of
      IGT or DM2.

PMID- 16886778
TI  - [Basal insulin levels in a Zulia State population in Venezuela].
AB  - This study examines the basal insulin levels in a population from Zulia state
      (Venezuela). A total of 1703 subjects (1175 women and 528 men) from five
      different sanitary regions (Maracaibo, La Guajira, Perija, Sur del Lago de
      Maracaibo, y Costa Oriental del Lago de Maracaibo) were studied. Weight, height,
      waist and hip circumferences, and blood pressure were determined. A blood sample
      was taken after a 12-h overnight fast to determine serum glucose, triglycerides,
      total cholesterol and HDL-C using enzymatic methods and insulin by
      radioimmunoassay. According to ATP III criteria two groups were established: a
      group without metabolic abnormalities (138 subjects) and a group with some
      metabolic abnormalities 84.8% of subjects of the non metabolic alteration groups
      and 80.4% of the group with some metabolic alteration were of mixed race. Non
      metabolic altered lean subjects (BMI <25 Kg/m2) had the lowest (p < 0.0001) basal
      insulin levels compared to the ones with overweight from the same group and the
      obese with metabolic abnormalities. This study proposes to consider a cutoff
      basal insulin levels of 13 microU/mL for women and 11 microU/mL for men, over 20
      years of age, in the Zulia state region of Venezuela.

PMID- 16886779
TI  - [Phenotyping and genotyping studies in a family with the compound heterozygosity
      deltabeta Thalassemia/beta(IVSII-849) Thalassemia].
AB  - The propositus is a two year old child with a severe hemolytic anemia and
      increased level of Hb F. The Hbs A, A2 and F were eluted and quantitated by
      cation exchange high-performance liquid chromatography (HPLC-CE). DNA was
      isolated from peripheral blood leukocytes by a salting-out extraction procedure.
      The beta globin gone was amplified and the presence of the beta thalassemia
      mutation was determined by PCR followed of Reverse Dot Blot. Her hematological
      parameters were as follows: Hb: 7.0 g/dL, Hct: 24.8%, VCM: 87.4 fl, CHCM: 27.8
      fl. The haemoglobin study showed an 97% increase of Hb F and Hb A2 normal. The
      molecular study suggested the presence of beta(IVSII-829) mutation in trans to
      deltabeta Thalassemia. The propositus inherited her mother's deltabeta
      thalassemia gene mutation and her father's beta(IVSH-829) mutation. This is the
      first time the diagnosis has been performed in a Venezuelan family at-risk of
      compound heterozygotes for beta-thalassemia and delta beta-thalassemia.

PMID- 16886780
TI  - [Metalloproteinases in tumor progression. Review].
AB  - The two biological characteristics that determine the malignancy of cancer are
      infiltration and metastasis. The study of these mechanisms is related to the
      invasion of tumoral cells and the relationship of these cells with their stroma,
      which interact producing the movement and accumulation of inflammatory cells, the
      formation of new blood vessels, multiplication of fibroblasts and the synthesis
      of the components of the extra cellular matrix production. Tumoral invasion is
      conditioned through various enzyme activities, in particular proteases which
      degrade the matrix, thus facilitating the progression of the tumor. The
      metalloproteinases (MMP) are a family of proteinases that play an important role
      in cancer as well as in numerous other diseases. MMP are, therefore, a potential
      factor in cancer therapy. Several synthetic MMP inhibitors have been developed
      and have shown successful anti-tumor activity in a variety of animal species, but
      in clinical studies of patients with advanced forms of cancer, this therapeutic
      strategy has not resulted as effective. In this article, due to the biological
      and clinical importance of this therapy, we summarize the current views on the
      role of metalloproteinases (MMP) in tumor promotion, proliferation, invasion,
      metastasis and angiogenesis.

PMID- 16886781
TI  - In praise of midwives.

PMID- 16886782
TI  - Student midwives raise concerns.

PMID- 16886783
TI  - Finding a voice.

PMID- 16886784
TI  - Routine commercial umbilical cord blood collection.

PMID- 16886785
TI  - Developing guidelines for the mental health care of mothers and mothers-to-be.

PMID- 16886786
TI  - Confidentiality and pregnant staff.

PMID- 16886787
TI  - Feathering the nest: what women want from the birth environment.
AB  - The National Childbirth Trust wants all women to be able to give birth with
      confidence and dignity, and believes it is important for women to begin
      motherhood feeling fit and well, good about themselves, and valued and supported
      by others. Good health and positive experiences can act as a buffer against the
      tiredness and demands of looking after a new baby. This paper draws on surveys
      conducted in 2003 and 2005 to describe what women want and need from birth
      environments, and how these factors can help or hinder them in having the kind of
      birth experience they desire.

PMID- 16886788
TI  - Midwifery today: past challenges and achievements inspire present practice.

PMID- 16886789
TI  - Challenging and inspiring: student winner gives her conference verdict.

PMID- 16886790
TI  - Assessment of a newborn: whose job--midwife or doctor?

PMID- 16886791
TI  - Onwards and upwards: where now for consultant midwives?

PMID- 16886792
TI  - Global health and the NHS.

PMID- 16886793
TI  - The Museo Ostetrico.

PMID- 16886794
TI  - In the light of recent Latin American research, are caesarean delivery rates in
      the UK too high?

PMID- 16886795
TI  - [Early seizures after acute ischemic stroke].
AB  - In order to determine predictive factors of early seizures (ES) after acute
      stroke and to estimate prognosis, we retrospectively examined clinical data of
      1,743 consecutive patients with acute ischemic stroke. The subjects were divided
      into two groups; an ES group (19 patients) and a non-ES group (1,724 patients).
      Multivariate statistical analysis revealed that the NIH-Stroke Scale score on
      admission (/10, OR, 1.1: 95% CI 1.04 to 1.13) and positive past history of
      cerebrovascular disease or brain injury (OR, 3.85: 95% CI 1.49 to 9.95) are
      significant factors to predict ES. There was no significant difference in the
      outcome between the two groups. A recurrence of seizures, after follow up for 4
      to 40 months, was observed only in one patient with a history of ES.

PMID- 16886796
TI  - [A steroid-responsive case of severe rhabdomyolysis associated with
      cytomegalovirus infection].
AB  - A 31-year-old man was admitted to our hospital, complaining of muscular weakness
      and pain in the legs one month after a common cold. On admission, neurological
      examinations demonstrated moderate weakness in the arms and mild weakness in the
      legs with decreased or diminished deep tendon reflexes, and mild dysphagia.
      Weakness was gradually extended to the arm, throat and respiratory muscles,
      requiring artificial ventilation. Laboratory examinations demonstrated increased
      levels of CK (upto 24,380 IU/L) and positive anti-cytomegalovirus (CMV) -IgM
      antibodies in the serum, and myogloburinuria. CMV was not detected in either the
      blood cells or muscles by PCR. There were no antibodies against viruses including
      Ebstein-Barr virus and HIV, in the serum. There were no autoantibodies related to
      collagen diseases in the serum. Systemic PET scan did not show any evidence of
      malignancy. Bone marrow biopsy did not show any atypical cells. Muscle MRI
      demonstrated mild atrophy with high intensity signals in part. Muscle biopsy
      demonstrated scattered necrotic and regenerated muscle fibers without
      inflammatory cell infiltration. The patient was therefore diagnosed as having
      rhabdomyolysis associated with CMV infection. After three courses of
      intravenously administered high dose methylprednislone over three days, muscle
      weakness improved gradually, and the serum CK level was normalized in two months.
      The patient recovered and was removed from artificial ventilation three months
      after the therapy. There were no sign of renal failure. Steroid therapy should be
      considered for the treatment of rhabdomyolysis or myopathy associated with CMV
      infection in order to prevent renal failure or fatal progression of the disease.

PMID- 16886798
TI  - [A case of non-herpetic acute limbic encephalitis associated with a type-2
      adenovirus infection].
AB  - This is a report of a 31-year-old woman with non-herpetic acute limbic
      encephalitis following a type-2 adenovirus infection. The patient was admitted to
      a hospital with high fever, severe liver dysfunction, and thrombocytopenia. Six
      days after admission, she became afebrile, and her liver dysfunction was
      normalized by conservative therapy. However, the patient started to experience
      generalized seizures that developed into status epileptics. The patient was then
      transferred to a referred hospital. Brain MR images revealed faint high-signal
      intensity in the bilateral limbic systems on FLAIR images. A CSF examination
      indicated mild pleocytosis. These findings suggested acute limbic encephalitis,
      which may have been mediated by an autoimmune reaction following some viral
      infection. Thus, steroid pulse therapy was started on the day of admission. The
      patient's condition, including the seizures and disturbances involving
      consciousness, improved gradually. The patient was discharged from the hospital
      in one month while still experiencing mild memory disturbances. Three months
      after onset of the illness, a T1-weighted MR image showed a linear high-signal
      intensity in the hippocampi, which indicated focal necrosis. Six months after
      onset, the patient's memory disturbance had been improved (her MMSE score was
      28/30 points). We investigated the titers of many viruses that are known to cause
      liver dysfunction and found that a titer of the type-2 adenovirus was
      significantly elevated within three weeks. Although the anti-voltage-gated
      potassium channel (VGKC) antibody was not detected in the patient's serum, it
      seems that the autoimmune reaction after the type-2 adenovirus infection may have
      caused the acute limbic encephalitis.

PMID- 16886797
TI  - [Transcortical sensory aphasia due to extensive infarction of left cerebral
      hemisphere].
AB  - We report a case of transcortical sensory aphasia occurred after extensive
      infarction of left cerebral hemisphere. A 68-year-old, right-handed man with
      atrial fibrillation suddenly developed cerebral embolism of left middle cerebral
      artery. He was treated conservatively, and the right hemiplegia, aphasia, apraxia
      in a slight degree and right hemispatial neglect in a slight degree consequently
      existed. MRI showed a large cortical and subcortical infarct lesion including the
      left Broca's area, central region, perisylvian area with Wernicke's area and
      temporal lobe. In contrast, neuropsychological evaluation using the Western
      Aphasia Battery (WAB) demonstrated transcortical sensory aphasia, e.g., fluency
      8, auditory comprehension 1. repetition 10 and object naming 2.4. In addition to
      preserved repetition, both linguistic prosody and affective prosody were well
      preserved. Most cases with transcortical sensory aphasia are known to occur with
      the lesion including temporo-parieto-occipital junction of dominant hemisphere.
      Our patient and a few other reported cases of transcortical sensory aphasia had a
      lesion in perisylvian area including Wernicke's area. Therefore, it is possible
      that their minor hemisphere worked selectively for repetition. Furthermore, we
      suggest that this patient presented dissociative aphasia that all the process of
      repetition and the function of linguistic and emotional prosody were represented
      in the right hemisphere and the other functions including comprehension of word
      meanings were existed in the left hemisphere. We believe that our case of
      transcortical sensory aphasia with dissociative aphasia gives a suggestion about
      the mechanism and localization of repetition and prosody in the whole system of
      language.

PMID- 16886799
TI  - [Sensory disturbance in the pulp of the fingertips in three patients with
      cervical myelitis].
AB  - We report three patients with cervical myelitis, with sensory disturbance at
      their fingertips. They exhibited the following clinical features in common:
      localized sensory disturbance in the pulp of the fingertips, with a positive
      Lhermitte's sign, but retained deep sensation. T2-weighted MR imaging
      demonstrated a swelling of the spinal cord at the C2 to C3 level, and a
      hyperintense lesion in the posterior region of the spinal cord at the same level
      in all patients. The characteristic symptoms of these three patients might be
      attributable to the somatotopy in the dorsal column at high cervical levels,
      because the afferent fibers innervating the fingertips occupy a much wider axial
      area at the high cervical spinal cord levels than the small surface area actually
      innervated by them.

PMID- 16886800
TI  - [A case of acute idiopathic autonomic neuropathy improved by intravenous
      immunoglobulin].
AB  - We describe a case of acute idiopathic autonomic neuropathy (AIAN) in which
      intravenous administration of immunoglobulin (IVIg) proved effective. A 32-year
      old man was admitted with orthostatic dizziness. Fever and headache first
      developed 24 days earlier, and persisted for 10 days, when orthostatic dizziness
      developed and prevented him from walking. Hypohidrosis, constipation and
      impotence also developed. Neurological examinations revealed no abnormalities.
      Cerebrospinal fluid obtained showed pleocytosis (26/microl) and an increased
      level of protein (70mg/dl). A head-up tilt test revealed that blood pressure
      decreased from 120/60mmHg when supine to 60/ 40 mmHg in a head-up position, and
      the patient complained of dizziness. Plasma noradrenaline concentration was
      26pg/ml when supine and 44pg/ml in a head-up position. Results of MIBG cardiac
      scintigraphy were normal. Dizziness disappeared after initiating IVIg (0.4
      g/kg/day). A head-up tilt test was performed 7 days after IVIg, revealing blood
      pressures of 106/61mmHg when supine and 103/71mmHg in a head-up position. These
      results suggest that IVIg should be considered as a choice to treat early AIAN.

PMID- 16886801
TI  - [Focal cortical dysplasia at the primary somatosensory cortex could manifest both
      intractable partial epilepsy and cortical reflex myoclonus].
AB  - We report a 31-year-old patient who suffered from the left foot motor seizure
      since 6 years of age. In addition to spontaneous seizures, the seizures tended to
      be triggered by somatosensory stimulus to the left foot. Recently, he developed
      irregular myoclonic jerks of the left foot. Neurologically, he had mild
      impairment of fine movements of the left foot, but otherwise no weakness or
      sensory disturbance was noted. Interictal spikes were frequently recorded at the
      vertex region, where ictal discharges also started during the video-EEG
      monitoring. Electrical stimulation of the left tibial nerve evoked giant cortical
      components of somatosensory evoked potentials and C-reflex.
      Magnetoencephalographic study of both interictal and jerk-locked averaged spikes
      located the equivalent current dipole of both activities at the left foot primary
      somatosensory cortex (SI), where 3 tesla MRI revealed a focal abnormality
      consistent with focal cortical dysplasia. The present non-invasive investigation
      suggests that focal cortical dysplasia at SI could manifest intrinsic,
      autonomous, epileptogenicity as well as extrinsic, stimulus-sensitive,
      hyperexcitability, which are clinically manifested as spontaneous seizures and
      cortical reflex myoclonus, respectively.

PMID- 16886802
TI  - [Medullary tegmentum lesion in a patients having intractable hiccups, nausea, and
      syncope].
AB  - A 61-year-old female, having intractable hiccups, nausea, and syncope. Her
      systolic blood presure decreased by 30 mmHg on sitting position from supine
      position. Sinus arrest lasting more than three seconds were detected 52 times per
      day by 24 hour Holter electrocardiography. Brain MRI disclosed a small
      hyperintense lesion in the medullary tegmentum on T2-weighted images. She was
      diagnosed as having a relapse of multiple screlosis and her symptoms were
      improved by administration of high dose methylprednisolone (1,000 mg per day x 3
      days) intravenously. In a patients, a stimulative lesion in the medullary
      tegmentum was suspected where the reflex centers of hiccups, nausea and blood
      pressure to exist. We are able to confirm a small hyperintense lesion in such a
      particular region by brain MRI. In case of syncope accompanied with intractable
      hiccups and nausea, we should consider a stimulative lesion in the medullary
      tegmentum. Moreover, sinus arrest other than orthostatic hypotension may be
      involved in the pathophysiology of syncope in correlation with the medullary
      tegmentum lesion.

PMID- 16886803
TI  - [A case of hypoxic encephalopathy with unilateral laminar necrosis].
AB  - We reported a 67-year-old woman with unilateral laminar necrosis caused by
      hypoxic encephalopathy. She presented with sudden onset of dyspnea,
      unconsciousness and left hemiplegia. Although diffusion-weighted MRI image of the
      brain 14 hours after onset was indistinct, MRI on the 4th day showed right
      laminar necrosis. Cerebral angiography demonstrated complete obstruction of the
      right proximal common carotid artery and severe stenosis of the left internal
      carotid artery. We speculate that chronic ipsilateral obstruction of the internal
      carotid artery may modify the unique distribution of laminar necrosis. As shown
      in this case, laminar necrosis can be demonstrated only on subsequent MRI. If
      clinical suspicion of hypoxic encephalopathy is high, repeated MRI may be
      appropriate.

PMID- 16886804
TI  - [CT findings of pulmonary hypertension].
AB  - For the treatment for pulmonary hypertension (PH), the differential diagnosis of
      its causal diseases is essential. To determine whether X-ray CT is useful for
      differentiating PH, we reviewed CT findings of 53 patients (18 men and 35 women,
      mean age of 44.9) given a diagnosis of PH, consisting of 25 with primary
      pulmonary hypertension (PPH), 18 with chronic pulmonary embolism (cPE), 6 with
      Eisenmenger syndrome, 5 cases of collagen diseases, 2 of acute PE, and 1 of cor
      pulmonale. The intrapulmonary distribution of CT findings (ground glass opacity
      [GGO], mosaic attenuation, striation and/or infiltration, and interlobular septal
      thickening) were reviewed and scored on a 4-point scale (grade 0: no findings, 1:
      involving one third of the lung, 2: involving one-two thirds, and 3: diffuse
      distribution) by two radiologists who reached a consensus. PPH showed
      preferentially diffuse distribution of GGO as compared with cPE (p<0.05).
      However, there was no apparent relationship between the pulmonary vascular
      resistance and the distribution of GGO in PPH cases. The mosaic attenuation
      pattern was more frequent in cPE (43%) than PPH (12% ; p<0.05). Striation and/or
      infiltration was observed in 36% of cPE, but only 4% of PPH. Interlobular septal
      thickening was seen in 16% of PPH, and 0% in cPE. Evaluation of CT findings is
      useful to differentiate PH.

PMID- 16886805
TI  - [Reactivation of Epstein-Barr virus is involved in the pathogenesis of
      lymphomatoid granulomatosis].
AB  - Recent studies point to a role of Epstein-Barr virus in the pathogenesis of
      lymphomatoid granulomatosis. Little is however known about the association of the
      pathogenesis of the disease with Epstein-Barr virus reactivation. A 46-year-old
      man presented with fever and general malaise. He had been admitted with fever of
      unknown origin 10 years previously. Chest radiographs and CT scans showed
      multiple nodular shadows in both lung fields. PET/CT showed strong accumulation
      in lung nodules, femoral muscle, lumbar subcutaneous nodule. He died of rapidly
      progressive neurological lesions. The definitive diagnosis of lymphomatoid
      granulomatosis was made from histological findings of the surgical biopsy
      specimen and at autopsy. Elevation of early antigen-IgG titer in serum was shown
      in this case. This result suggests that reactivation of Epstein-Barr virus is
      involved in the development of the disease.

PMID- 16886806
TI  - [A case of carcinoma with sarcomatoid elements in the middle mediastinum].
AB  - We describe a 63-year-old man who, while under treatment as an outpatient for
      adult onset Still's disease (AOSD), developed edema of the extremities and
      mediastinal tumor was observed on a chest X-ray film and a chest CT scan. He was
      not pathologically diagnosed at first and received radiation therapy with a total
      dose of 30 Gy. Transbronchial biopsy was carried out because the tumor enlarged,
      and the tumor invasion was observed in the left lumen of the main bronchus.
      Histological findings suggested a diagnosis of carcinoma with sarcomatoid
      elements (CSE). Further radiation therapy with a dose of 20 Gy was unsuccessful;
      his condition gradually worsened and the patient died. The autopsy findings
      demonstrated that CSE developed in the middle mediastinum, and the other organs
      were not involved. From an embryologic standpoint, there seemed to be some
      possible differential diagnoses, such as a pleomorphic carcinoma as a subtype of
      lung cancer, and CEA as a metastatic mediastinal lymph node cancer of unknown
      origin or a primary mediastinal lymph node cancer. Like the present case, tumors
      developed in the middle mediastinum with rapid progression are rare. We report a
      case, that was difficult to diagnose and treat.

PMID- 16886808
TI  - [An autopsy case of obliterative bronchiolitis associated with Stevens-Johnson
      syndrome].
AB  - We reviewed an autopsied 27-year-old female with obliterative bronchiolitis
      associated with Stevens-Johnson syndrome. She had a history of Stevens-Johnson
      syndrome at age 10 years old and was treated with corticosteroids. Two months
      after the onset of dermatitis, the patient complained of dyspnea on exertion. The
      chest radiograph showed hyperinflation, and pulmonary function tests revealed
      obstructive impairment. The respiratory failure progressed due to respiratory
      tract infection and pneumothorax. She underwent thoracoscopic cyst surgery for
      right pneumothorax. Although the patient was clinically diagnosed as having
      obliterative bronchiolitis and received corticosteroids therapy and mechanical
      ventilation, she died of progressive respiratory failure 17 years after the onset
      of Stevens-Johnson syndrome. On autopsy, the macroscopic appearance of both lungs
      showed multiple white nodules in the centrilobular lesion corresponding to the
      obliteration of the small bronchioli. The microscopic appearance revealed
      constrictive bronchiolitis in the membranous bronchioli of both lungs associated
      with secondary bronchiectasis caused by superimposed infection.

PMID- 16886807
TI  - [A case of pulmonary tumor embolism presenting with an initial manifestation of
      urothelial carcinoma].
AB  - A 64-year-old man presented with fever, chest pain, and bloody sputum. Chest
      computed tomography showed multiple, irregularly shaped infiltrative shadows in
      the subpleural regions of both lung fields. Out of the 6 sputum cytology
      specimens, only one specimen suggested malignancy. Furthermore, no malignant
      cells were detected in the bronchoalveolar lavage fluid. A video-assisted lung
      biopsy yielded a diagnosis of pulmonary tumor embolism was made. The primary
      lesion of this pulmonary metastatic cancer was urothelial carcinoma, which was
      not detected by contrast-enhanced computed tomography of the abdomen. This case
      is particularly unusual because it is difficult to establish an ante-mortem
      diagnosis of pulmonary tumor embolism, and there have been only a few previous
      reports regarding pulmonary tumor embolism from a urothelial tumor.

PMID- 16886809
TI  - [A case of cryptogenic organizing pneumonia accompanied by large bullae].
AB  - A 66-year-old man complaining of fever was given intravenous antibiotic therapy,
      but he did not improve. After subsequent admission, chest X-ray film and computed
      tomography scans showed large bullae and consolidation in the right lung field. A
      transbronchial lung biopsy specimen revealed infiltration of mononuclear cells in
      alveolar septa and organizing lesions in alveolar ducts. We considered this case
      to be cryptogenic organizing pneumonia (COP) from its clinical course and
      pathological findings. Treatment with corticosteroid resulted in disappearance of
      the large bullae and consolidations. COP accompanied by large bullae is very
      rare. The large bullae may have been caused by check-valve mechanism.

PMID- 16886810
TI  - [A case of primary Sjogren' s syndrome with pathological findings resembling
      multicentric Castleman' s disease showed multiple nodular opacities on chest CT
      scans].
AB  - A 49-year-old woman with primary Sjogren's syndrome a few years previously was
      admitted to our hospital complaining of tongue and skin eruptions, swelling of
      the face and neck and for examination of liver injury and hypereosinophilia. A
      blood test revealed leukocytosis with eosinophilia, mild liver injury, polyclonal
      hypergammaglobulinemia, and positive results for anti-nuclear antibody, anti-SS-A
      antibody and anti-SS-B antibody. Chest CT scan showed multiple nodular opacities
      with cavities in peripheral regions of both lungs. Biopsy specimens from the
      right lower lobe obtained by video-assisted thoracoscopy revealed marked
      infiltration of plasma cells and lymphocytes in alveolar lumina, lymph follicles
      with germinal centers in other areas of the pulmonary parenchyma, and lymphocytes
      infiltrate in alveolar wall adjacent bronchi and bronchioles. The histological
      diagnosis was pulmonary involvement of multicentric Castleman's disease. This was
      a rare case of Sjogren's syndrome accompanied by pathological findings of
      multicentric Castleman' s disease showed multiple nodular opacities in chest CT
      scans.

PMID- 16886811
TI  - [A case of pulmonary eosinophilic granuloma that remitted after cessation of
      smoking].
AB  - A 43-year-old man was admitted to our hospital because of productive cough and an
      abnormal chest radiograph. He had smoked one pack of cigarettes per day for 23
      years. Chest radiograph on admission showed diffuse reticulo-linear infiltrates,
      most prominent in both upper lung fields. Chest HRCT scan showed multiple
      micronodules, cavitated nodules, and thick-walled cysts with ground-glass
      attenuation. These radiographic findings suggested pulmonary eosinophilic
      granuloma (PEG). Histological findings of the biopsy specimen obtained from video
      assisted thoracoscopy demonstrated granulomatous lesions consisting of S-100
      protein-positive Langerhans cells with infiltration of eosinophils and fibrous
      lesions (starfish-like fibrosis). A definitive diagnosis of PEG was made, and he
      immediately ceased smoking. The symptoms and radiographic findings markedly
      improved within 3 months after cessation of smoking. Chest HRCT on the final scan
      revealed that nodules and almost all cystic lesions vanished. He resumed smoking
      without any sign of recurrence.

PMID- 16886812
TI  - [Three cases of indium lung].
AB  - The production of indium tin oxide (ITO) has been increasing during the past
      decade because of its use in liquid crystal and plasma display panels. Following
      the first report on lethal lung injury in a ITO worker in 2001, we began
      pulmonary check-ups for 115 workers in the plant in our capacity of industrial
      physicians of the plant. Hence, we report interstitial pulmonary disease in 3
      workers who had engaged in wet-surface grinding of ITO for 8 to 12 years and had
      significant lung injuries. The serum indium level and serum concentration of KL-6
      were significantly elevated in all 3 cases. One non-smoker case among them showed
      severe obstructive changes on spirometry and had an episode of repeated bilateral
      pneumothorax before and during the follow-up period. All 3 cases showed both
      interstitial and/or emphysematous changes on HRCT. It is suggested that inhaled
      indium compounds can cause a new and unique interstitial pulmonary disease.

PMID- 16886813
TI  - [A case of angioimmunoblastic T-cell lymphoma with interstitial shadow which
      disappeared after injection of hydrocortisone].
AB  - A case of angioimmunoblastic T-cell lymphoma (AITL) was reported. A 56-year-old
      woman was admitted because of high fever and systemic lymphademopathy. Her chest
      X-ray on admission showed mediastinal and bilateral hilar lymphademopathy (BHL)
      and interstitial shadows in both lower lung fields. Chest CT scan revealed
      thickening of interlobular septum and bronchovascular bundles. There was a
      remarkable elevation in serum soluble interleukin-2 receptor. A biopsy of
      cervical lymph nodes for histopathological examination revealed AITL. After
      intravenous injection of 200mg of hydrocortisone for 7 days, the interstitial
      shadows and BHL disappeared. It was suspected that interstitial shadow was caused
      by pulmonary infiltration of AITL.

PMID- 16886814
TI  - Quantum dots in medical technology.
AB  - During the past few years, the rapidly emerging technology of quantum dots has
      started to have an impact on the techniques of molecular and cellular imaging in
      medicine. Their advantages are examined here.

PMID- 16886815
TI  - The evolution of lab-on-A-chip: the Micro-Tele-BioChip.
AB  - The vision of multianalyte point-of-care diagnostics (POCT) is a handheld device
      that every patient can use easily for continuous monitoring of, for example, drug
      efficiency in the treatment of chronic diseases. Technologies are needed to
      realise this vision. Some are described here in the prototyping and industrial
      production of a disposable chip for the Micro-Tele-BioChip (muTBC) platform.
      muTBC is a technology platform that can be customised to meet specific
      requirements in drug safety and POCT.

PMID- 16886816
TI  - New markets for small and smart medical products.
AB  - Miniaturised devices that employ micro- and nanotechnologies will play a major
      role in future medical treatment and technology. In addition to 35 already
      commercialised nanomedical products, there are new market opportunities on the
      horizon including self-medication with small and smart devices. These and their
      drivers as well as current hurdles are examined here.

PMID- 16886817
TI  - Improving the deliverability of PCI catheters.
AB  - A recent study assessing views of interventional cardiologists on the performance
      of catheters used in angioplasty, also known as percutaneous coronary
      interventions (PCI), indicates that there is a need for improvement in the
      catheter. The particular areas of improvement are reviewed here with some
      hypotube shaft solutions that promise to improve catheter deliverability.

PMID- 16886818
TI  - Simulated testing in medical device design.
AB  - Bench-top testing of a typical catheter is described here to show how early
      prototype evaluation can decrease product development time. Trackability and
      pushability are assessed and compared using some novel laboratory tests, which
      can be applied to a variety of medical devices.

PMID- 16886819
TI  - US regulation of Advertising and promotional materials.
AB  - Medical device manufacturers do not always properly control the development of
      new or modified promotional labelling and advertising materials. This lack of
      control can lead to unexpected regulatory problems. This article discusses United
      States requirements for these materials and the type of controls that companies
      should exercise.

PMID- 16886820
TI  - Why one healthcare IT market in Europe is essential.
AB  - The successful international interoperability programme, IHE, should be the model
      to use for a Europe-wide ehealth solution. This is advocated by COCIR, the
      European Coordination Committee of the Radiological, Electromedical and
      Healthcare IT Industry, which also calls on the European Commission to support
      this industry initiative.

PMID- 16886822
TI  - Microelectrodischarge machining.

PMID- 16886821
TI  - The innovator will prevail in glucose monitoring.
AB  - As well as the expanding diabetes market for glucose-monitoring devices, there
      are other applications for these products and opportunities for companies with
      the will to innovate. One area that is explored here is the intensive care unit.

PMID- 16886823
TI  - With shortage of nurses, I.T. becomes more essential.

PMID- 16886825
TI  - Mobile apps: plenty of choices, challenges.

PMID- 16886824
TI  - Nursing I.T.: from stations to bedside.

PMID- 16886826
TI  - Measuring outsourcing's effectiveness.

PMID- 16886827
TI  - A partner to go with the flow.

PMID- 16886828
TI  - Readers perspectives. The health care industry can develop and adopt standards
      based, interoperable clinical information systems.

PMID- 16886829
TI  - ECG of the month. Anxiety attack. Myocardial ischemia.

PMID- 16886830
TI  - Myalgias and palpable muscle nodules in a twenty-two year old man.

PMID- 16886831
TI  - An adult male presenting with an umbilical nodule.

PMID- 16886832
TI  - A 30-year-old man with syncope and melena.

PMID- 16886833
TI  - Calvarial and scalp metastases: an unusual presentation of non-small-cell lung
      cancer.
AB  - We report the case of a 64-year-old woman who presented with scalp and skull
      masses. Histological examination confirmed the diagnosis of metastatic tumor from
      non-small-cell lung cancer. To our knowledge, this is the sixth case reported in
      the English literature. Although the occurrence of the distant neoplastic spread
      was a preterminal event, local electron beam irradiation effected significant
      resolution of the metastatic tumors.

PMID- 16886834
TI  - Hurricane Katrina's impact on infectious disease surveillance.

PMID- 16886835
TI  - Paraesophageal hernia secondary to failed Nissen fundoplication mimicking lung
      abcess.
AB  - A 9 1/2-month-old girl was transferred to our institution for evaluation and
      treatment of a lung abscess. Presenting symptoms included low-grade fever,
      irritability, diarrhea, and tachypnea. Chest radiograph showed a dense opacity
      with an air-fluid level in the lower portion of the right hemithorax. When the
      radiograph was reviewed carefully, surgical clips from a previous Nissen
      fundoplication were visible within the area of consolidation. A barium study
      revealed evidence of a large paraesophageal hernia with an air fluid level, and
      no evidence of a lung abscess. The patient had a laparoscopic revision of the
      Nissen, which had slipped superiorly, and an esophageal hernia repair.
      Postoperatively, the patient did well and was discharged without any
      complications.

PMID- 16886836
TI  - Falsely high ankle-brachial index predicts major amputation in critical limb
      ischemia.
AB  - Falsely high ankle-brachial index (ABI) values are associated with an adverse
      clinical outcome in diabetes mellitus. The aim of the present study was to verify
      whether such an association also exists in patients with chronic critical limb
      ischemia (CLI) with and without diabetes. A total of 229 patients (74 +/- 11
      years, 136 males, 244 limbs with CLI) were followed for 262 +/- 136 days.
      Incompressibility of lower limb arteries (ABI > 1.3) was found in 45 patients,
      and was associated with diabetes mellitus (p = 0.01) and renal insufficiency (p =
      0.035). Limbs with incompressible ankle arteries had a higher rate of major
      amputation (p = 0.002 by log-rank). This association was confirmed by
      multivariate Cox regression analysis (relative risk [RR] 2.67; 95% CI 1.27-5.64,
      p = 0.01). The relationship between ABI > 1.3 and amputation rate persisted after
      subjects with diabetes and renal insufficiency had been removed from the analysis
      (RR 3.85; 95% CI 1.25-11.79, p = 0.018). Dividing limbs with measurable ankle
      pressure according to tertiles of ABI, the group in the second tertile (0.323 <
      or = ABI < or = 0.469) had the lowest amputation rate (4/64, 6.2%), and a U
      shaped association between the occurrence of major amputation and ABI was
      evident. No association was found between ABI and mortality. In conclusion, this
      study demonstrates that falsely high ABI is an independent predictor of major
      amputation in patients with CLI.

PMID- 16886837
TI  - Sarpogrelate, a 5-hT2A receptor antagonist in intermittent claudication. A phase
      II European study.
AB  - This was a multinational, multicentre, double-blind Phase II study in Europe to
      evaluate the efficacy and safety of two dose regimens (200 mg bid and 200 mg tid)
      of sarpogrelate (MCI-9042, 5-HT2A receptor antagonist) compared to placebo in
      patients with stable, moderately severe intermittent claudication. Following a
      single-blind placebo run-in period of 6 weeks, 364 (309 male and 55 female)
      patients (59.2 +/- 8.4 years, mean +/- SD) were randomized to receive
      sarpogrelate 200 mg bid, 200 mg tid or placebo for 24 weeks with a follow-up of 8
      weeks. The primary objective was the increase of absolute claudication distance
      (ACD) at the end of treatment (week 24) compared to placebo. Analysis of
      covariance (ANCOVA) was performed on the log-transformed percentage of baseline
      ACD: loge(ACD/baseline). A responder analysis (defined as a > or = 50%
      improvement in ACD) was also performed. There was a marked training/placebo
      effect on the ACD which persisted up to 16 weeks. At 24 weeks the primary
      objective did not reach statistical significance (200mg bid vs placebo, p =
      0.225; 200mg tid vs placebo, p = 0.580). In the responder analysis, 200 mg bid
      showed a statistically significant difference vs placebo (p = 0.035). In the
      exploratory analysis with completers (patients completing all treadmill tests),
      there was a statistical difference in ACD/baseline change for 200 mg bid (p =
      0.035) and in the responder analysis for 200 mg tid (p = 0.044) at 24 weeks
      compared to placebo. Both treatments showed a carry-over effect for ACD during
      the 8-week follow-up (weeks 28-32). The treatment was well tolerated and no
      clinically significant safety concerns were reported. In conclusion, the study
      results confirm that sarpogrelate is well tolerated and although the primary
      endpoint failed to reach statistical significance, the responder analysis showed
      an increased absolute walking distance, which makes a further trial warranted,
      including a larger population, and possibly also a longer treatment period.

PMID- 16886838
TI  - The effect of iron status on vascular health.
AB  - The effect of increased iron stores on the progression of atherosclerosis and
      endothelial health remains inconclusive. This study was designed to evaluate the
      relationship between hemochromatosis genotypes, serum ferritin levels and
      presymptomatic vascular abnormalities in a cohort of healthy subjects. Carotid
      intima-media thickness (CIMT) and brachial flow-mediated vasodilation (FMD) were
      assessed by high-resolution ultrasound in 907 male (47 +/- 10 years) participants
      enrolled in the Firefighters and their Endothelium (FATE) study. Analyses of the
      hemochromatosis C282Y, H63D and S65C alleles were simultaneously determined by a
      single nucleotide polymorphism (SNP) primer extension method. It was found that
      brachial FMD was not related to serum ferritin or hemochromatosis genotype
      status. The presence of a hemochromatosis-associated genotype (n = 18) or
      heterozygosity for the C282Y genotype (n = 98) was not associated with an
      increased mean CIMT. After adjustment for conventional risk factors, serum
      ferritin was also not associated with mean CIMT. In conclusion, neither ferritin
      nor a hemochromatosis genotype was related to brachial endothelial function or
      carotid atherosclerosis. The present study does not support the hypothesis that
      mild to moderately increased iron stores are associated with enhanced
      atherosclerosis risk.

PMID- 16886839
TI  - Type-2 diabetes and carotid stenosis: a proposal for a screening strategy in
      asymptomatic patients.
AB  - The objective of this prospective observational study was to establish the
      prevalence of carotid atherosclerosis in an asymptomatic diabetic population and
      to determine predictive factors for a screening optimization. A total of 300
      consecutive type-2 diabetic subjects (166 males, 134 females) underwent a
      physical examination and duplex carotid scanning. Patients with a recent
      cerebrovascular event (< or = 6 weeks) or previous carotid surgery were excluded.
      The prevalence of carotid stenosis > or = 60% or occlusion was 4.7%; the
      prevalence of carotid atherosclerosis was 68.3%. Risk factors for stenosis > or =
      60% or occlusion were the presence of diabetic retinopathy (OR: 3.62; 95% CI:
      1.12-11.73), ankle-brachial index (ABI) <0.85 (OR: 3.94; 95% CI: 1.21-12.84) and
      a personal history of neurological disorders (OR: 4.54; 95% CI: 1.16-17.81).
      Being female was a protective factor (OR: 0.09; 95% CI: 0.01-0.78). The two
      factors in the analysis limited to the male population were an ABI < 0.85 (OR:
      3.66; 95% CI: 1.04-12.84) and a personal history of coronary heart disease (OR:
      3.34; 95% CI: 1.01-11.01). If male diabetics without either of these two factors
      are excluded, the negative predictive value for carotid stenosis is 96.6%. In
      conclusion, the prevalence of atherosclerotic carotid disease in diabetic
      patients is high. In these patients, the probability of finding >60% stenosis is
      highest among men with a history of coronary heart disease or an ABI <0.85.

PMID- 16886841
TI  - Repair of a splenic artery aneurysm using a novel balloon-expandable covered
      stent.
AB  - We describe a case of endovascular exclusion of a splenic artery aneurysm. The
      repair utilized a novel balloon-expandable stent-graft.

PMID- 16886840
TI  - Folic acid improves endothelial dysfunction in type 2 diabetes--an effect
      independent of homocysteine-lowering.
AB  - Diabetes is associated with endothelial dysfunction, which in part may be related
      to uncoupling of the endothelial nitric oxide (NO) synthase enzyme, thus reducing
      the availability of NO. As folates may potentially reverse the uncoupling of NO
      synthase, we wanted to determine whether folic acid supplementation could
      modulate endothelial function and markers of inflammation in patients with type 2
      diabetes without vascular disease. Nineteen patients with type 2 diabetes were
      treated with folic acid (10mg/day for 2 weeks) versus placebo in a randomized,
      placebo-controlled, cross-over study with an 8-week washout period between
      treatments. Fasting endothelium-dependent flow-mediated dilatation (FMD) of the
      brachial artery, endothelium-independent nitroglycerin-mediated dilatation (NMD),
      plasma homocysteine, serum lipids, folate, and inflammatory markers (high
      sensitivity C-reactive protein, soluble intercellular adhesion molecule-1 and
      vascular cell adhesion molecule-1, interleukin-18, tumor necrosis factor-alpha)
      were assessed after each 2-week treatment period. Folic acid supplementation
      significantly increased folate levels and lowered plasma homocysteine levels.
      Folic acid significantly improved FMD compared to placebo (5.8 +/- 4.8% vs 3.2 +/
      2.7%, p = 0.02). There were no significant effects of folic acid supplementation
      on lipids, NMD, or the inflammatory markers. There was no relationship between
      the change in homocysteine and the improvement in FMD. Thus, 2 weeks of folic
      acid supplementation can improve endothelial dysfunction in type 2 diabetics
      independent of homocysteine-lowering, but does not modulate markers of
      inflammation.

PMID- 16886842
TI  - Potential role of the Slit/Robo signal pathway in angiogenesis.
AB  - Intensive investigations on angiogenesis and vasculogenesis have increased our
      understanding of molecular mechanisms of blood vessel formation during pathologic
      and developmental conditions. However, endothelial cells (ECs), the main
      component of vasculature, are heterogeneous, as revealed by our phenotypic and
      molecular biological studies in the laboratory, and it is still hard to
      adequately understand the molecular mechanisms of angiogenesis and
      vasculogenesis. Indeed, there are several major ligand/receptor signal pathways:
      VEGF/VEGFR, Jagged-1/Notch, Wnt ligand/frizzled receptor, and ephrin/Eph; each of
      which having distinct and independent roles during vascular formation. In this
      review, we focus on the angiogenic effect of the Slit and Robo signal pathway
      that was formally known as neuronal axon guidance. Among the existing vascular
      signals, this pathway is the most recently found ligand/receptor vascular signal,
      and may play important physiological roles as other major receptor/ligand signals
      do. Here, we briefly address: (1) the background of Slit and Robo families; (2)
      expression patterns of Slit and Robo; (3) functional roles of the Slit/Robo
      pathway in vascular formation; and (4) confronting tasks of this novel vascular
      pathway in the near future. Together, a summary of these data suggest the
      essential role of the Slit/Robo pathway in angiogenesis, and may explain why
      multiple vascular signals exist in heterogenic endothelial cells.

PMID- 16886843
TI  - Ultrasound-detected carotid plaque as a predictor of cardiovascular events.
AB  - Ultrasound detection of carotid plaque can be performed with equipment that is
      available in many clinical settings and can identify patients at increased risk
      of cardiovascular (CV) disease. We reviewed the literature to determine the CV
      risk factors associated with the presence of carotid plaque and whether its
      presence is associated with the presence and extent of coronary artery disease. A
      MEDLINE search subsequently was performed to determine whether carotid plaque
      burden predicts future CV events. Studies that had more than 300 subjects and
      reported hazard ratios or relative risk estimates for CV events, or data from
      which these values could be calculated, were included. References from identified
      studies also were examined for inclusion in the review. Nine studies met these
      criteria. Although there was not a uniform definition of carotid plaque, eight
      studies found that the presence of carotid plaque predicted incident CV death
      and/or myocardial infarction. In several studies, this relationship persisted
      after adjustments for risk factors. Ultrasound detection of carotid plaque is a
      straightforward, inexpensive, and safe tool that has the potential to be used in
      an office setting to help clarify a patient's CV risk.

PMID- 16886844
TI  - Images in vascular medicine. Persistent sac enlargement after conventional
      replacement of an inflammatory aortic aneurysm.

PMID- 16886845
TI  - Images in vascular medicine. Undiagnosed fatal mesenteric ischemia in acute type
      B aortic dissection.

PMID- 16886846
TI  - Images in vascular medicine. Atypical aortic coarctation.

PMID- 16886847
TI  - Is duplex surveillance of value after leg vein bypass grafting? Davies AH, Hawdon
      AJ, Sydes MR, Thompson SG, on behalf of the VGST participants. circulation 2005;
      112: 1985-91.

PMID- 16886848
TI  - Acoustic analysis of voice in patients treated by reconstructive subtotal
      laryngectomy. Evaluation and critical review.
AB  - Aim of this investigation was to analyse the voice in a group of 20 patients
      submitted to supracricoid partial laryngectomy (cricohyoidopexy, sparing two
      arytenoids) by the Multi Dimensional Voice Programme acoustic analysis system.
      Results revealed the following sound characteristics: high rate of noise, lack of
      periodic component of the signal, high rate of segments with no sound signal,
      vocal segments with marked air-turbulent flow, variation amplitude and frequency
      coefficients doubled compared to normal values, average fundamental frequency, if
      present, extremely variable and unsteady. These results show that the phonatory
      ability of the residual larynx, due to the altered anatomo-physiology of the
      structure after surgery, has to be completely re-estimated. In fact, the residual
      larynx determines a definitely reduced periodic acoustic signal, rich in noise
      and which can not be modulated. Good phonatory results of this treatment are
      basically due to preservation of a still understandable (but not perfect!) speech
      which, by ensuring the subjects' speech ability, overcomes and has little
      influence on the really poor quality of the vocal signal in these patients.
      However, the patient obtains a "new voice" as far as concerns acoustic features
      and this is very important for communication and social life. Moreover, the
      possibility of objectively estimating acoustic vocal function ability allows
      monitoring of the trend and results of possible speech therapy and/or
      phonosurgical rehabilitation treatment which should start from new anatomical and
      physiological bases, as well as from the new physical acoustic mechanism of
      signal production.

PMID- 16886849
TI  - Auditory cortical responses in patients with cochlear implants.
AB  - Currently, the most commonly used electrophysiological tests for cochlear implant
      evaluation are Averaged Electrical Voltages (AEV), Electrical Advisory Brainstem
      Responses (EABR) and Neural Response Telemetry (NRT). The present paper focuses
      on the study of acoustic auditory cortical responses, or slow vertex responses,
      which are not widely used due to the difficulty in recording, especially in young
      children. Aims of this study were validation of slow vertex responses and their
      possible applications in monitoring postimplant results, particularly restoration
      of hearing and auditory maturation. In practice, the use of tone-bursts, also
      through hearing aids or cochlear implants, as in slow vertex responses, allows
      many more frequencies to be investigated and louder intensities to be reached
      than with other tests based on a click as stimulus. Study design focused on
      latencies of N1 and P2 slow vertex response peaks in cochlear implants. The study
      population comprised 45 implant recipients (aged 2 to 70 years), divided into 5
      different homogeneous groups according to chronological age, age at onset of
      deafness, and age at implantation. For each subject, slow vertex responses and
      free-field auditory responses (PTAS) were recorded for tone-bursts at 500 and
      2000 Hz before cochlear implant surgery (using hearing aid amplification) and
      during scheduled sessions at 3rd and 12th month after implant activation. Results
      showed that N1 and P2 latencies decreased in all groups starting from 3rd through
      12th month after activation. Subjects implanted before school age or at least
      before age 8 yrs showed the widest latency changes. All subjects showed a
      reduction in the gap between subjective thresholds (obtained with free field
      auditory responses) and objective thresholds (obtained with slow vertex
      responses), obtained in presurgery stage and after cochlear implant. In
      conclusion, a natural evolution of neurophysiological cortical activities of the
      auditory pathway, over time, was found especially in young children with
      prelingual deafness and implanted in preschool age. Cochlear implantation appears
      to provide hearing restoration, demonstrated by the sharp reduction of the gap
      between subjective free field auditory responses and slow vertex responses
      threshold obtained with hearing aids vs. cochlear implant.

PMID- 16886850
TI  - Cochlear microphonic potential recorded by transtympanic electrocochleography in
      normally-hearing and hearing-impaired ears.
AB  - The cochlear microphonic is a receptor potential believed to be generated
      primarily by outer hair cells. Its detection in surface recordings has been
      considered a distinctive sign of outer hair cell integrity in patients with
      auditory neuropathy. This report focuses on the results of an analysis performed
      on cochlear microphonic recorded by transtympanic electrocochleography in
      response to clicks in 502 subjects with normal hearing threshold or various
      degrees of hearing impairment, and in 20 patients with auditory neuropathy.
      Cochlear microphonics recorded in normally-hearing and hearing-impaired ears
      showed amplitudes decreasing by the elevation of compound action potential
      Cochlear microphonic responses were clearly detected in ears with profound
      hearing loss. After separating recordings according to the presence or absence of
      central nervous system pathology (CNS+ and CNS-, respectively), cochlear
      microphonic amplitude was significantly higher in CNS+ than in CNS- subjects with
      normally-hearing ears and at 70 dB nHL compound action potential threshold.
      Cochlear microphonic responses were detected in all auditory neuropathy patients,
      with similar amplitudes and thresholds to those calculated for normally-hearing
      CNS- subjects. Cochlear microphonic duration was significantly higher in auditory
      neuropathy and normally-hearing CNS+ patients compared to CNS- subjects. Our
      results show that: 1. cochlear microphonic detection is not a distinctive feature
      of auditory neuropathy; 2. CNS+ subjects showed enhancement in cochlear
      microphonic amplitude and duration, possibly due to efferent system dysfunction;
      3. long-lasting, high frequency cochlear microphonics with amplitudes comparable
      to those obtained from CNS- ears were found in auditory neuropathy patients. This
      could result from a variable combination of afferent compartment lesion, efferent
      system dysfacilitation and loss of outer hair cells.

PMID- 16886851
TI  - Clinical examination of labyrinthine-defective patients out of the vertigo
      attack: sensitivity and specificity of three low-cost methods.
AB  - Many reports have appeared in the medical literature concerning the clinical
      examination at the bedside of patients with vertigo and, even if few
      controversial opinions exist, the observation of one or more kinds of nystagmus
      is generally regarded as suggesting an organic aetiology. So far, the presence of
      nystagmus has been generally considered to be crucially important for clinicians
      who are daily asked to differentiate between an "organic" cause of vertigo (for
      example, a labyrinthine dysfunction) and a "non-organic" cause of vertigo, such
      as a panic disorder. Albeit, it should not be forgotten that the central nervous
      system is able to resolve the asymmetry of vestibulo-ocular reflexes, due to a
      peripheral vestibular failure, by means of compensatory mechanisms so that
      nystagmus is rapidly abolished after the acute attack of vertigo. In addition,
      visual fixation elicits sub-cortical inhibitory pathways to the vestibular nuclei
      so that spontaneous nystagmus is remarkably reduced by light. In order to more
      easily detect nystagmus, attempts have been made to minimize the interference of
      visual fixation by means of positive lenses (Frenzel's glasses) and light
      occluding masks with infrared cameras (videonystagmoscopy) which have in part
      replaced direct observation of the patient's eyes, albeit no systematic
      validation of the advantages has been reported yet. To investigate the usefulness
      of these 3 low-cost methods to detect nystagmus, 528 outpatients presenting
      peripheral vestibular hypofunction, diagnosed by a complete audiological and
      vestibular examination, including caloric tests, were enrolled in the present
      study, while 133 subjects with normal vestibular function acted as a control
      group. All patients and control subjects underwent a standardized clinical
      examination based on search for spontaneous, positioning and head-shaking
      nystagmus detected by direct observation of patient's eyes, Frenzel's glasses and
      videonystagmoscopy. Specificity of the three techniques were 35.6, 43.7 and 91.6,
      whilst sensitivity was 88.7, 88.7 and 84.2, respectively. Finally, discriminant
      analysis based on the presence/absence of at least one kind of nystagmus was
      computed for each technique and showed that videonystagmoscopy allowed the
      examiner to correctly classify both pathological and normal subjects more
      frequently (> 77% of cases) than the other two methods (about 50%). It is
      concluded that only videonystagmoscopy is an acceptable technique for screening a
      labyrinth defect in a population of outpatients with vertigo.

PMID- 16886852
TI  - Surgical treatment of nasal septal perforations. Our experience.
AB  - Septal perforations are difficult problems that the otolaryngologist has to
      solve. In fact, the otolaryngologist has to identify the cause, which in most
      cases is either iatrogenic or idiopathic, to decide upon the need for surgery,
      and select the most suitable surgical technique of those currently available, for
      the case under consideration. All surgical procedures, aimed at repair of nasal
      septal perforations, are based on two main principles, namely repair using
      mucosal, mucoperichondrial, and/or mucoperiosteal flaps from the nasal cavity, or
      with connective tissue autograft, to be interposed between the mucosal flaps.
      Surgical repair of septal perforation can be carried out using either the "closed
      technique" or "open technique". The advantage of the former is that it does not
      leave any external scar. However, drawbacks related to difficulties due to the
      narrow operating field may be encountered. Many surgeons prefer the "open"
      technique, as it offers a wider operating field, thus allowing better access to
      the superior and posterior margins of the perforation (especially in large and/or
      posterior perforations), and offering binocular vision. The present report
      focuses on a short critical examination of the various surgical procedures
      described in the literature, in the attempt to identify, based also on personal
      experience, the most suitable techniques to repair septal perforations. A novel
      technique is presented for the surgical treatment of some types of perforations,
      which has not, so far, been described in the literature.

PMID- 16886853
TI  - Acoustic changes in voice after surgery for snoring: preliminary results.
AB  - All surgical procedures for treatment of snoring and obstructive sleep apnoea
      modify the anatomical structure of the upper airways and the resonance
      characteristics of the vocal tract; this can lead to a modification in voice
      quality. Purpose of this study was to evaluate the possible modifications of the
      fundamental frequency (F0) and of the frequency and amplitude of the first (F1)
      and second (F2) formants of the 5 Italian vowels after different surgical
      procedures for snoring, to verify if and how these operations can influence voice
      quality. A total of 40 snoring or obstructive sleep apnoea syndrome patients, not
      affected by laryngeal, pulmonary or neurologic disorders likely to alter voice
      production, were selected for the study. All were submitted to acoustic voice
      analysis prior to surgery and again 1 month after discharge. F0 was unchanged.
      The frequency of F1 of the vowel /a/ audio of F2 of the vowel /e/ were
      significantly higher, while F1 of /i/ and F2 of /o/ and /u/ were significantly
      lower compared to pre-operative values. The modifications in the anatomical
      structure and volume of the vocal tract, induced by the surgical procedures used
      for the treatment of snoring, can modify the values of the formants and, as a
      consequence, quality of the voice. This change can be detected not only by means
      of the acoustic analysis but also by the patient itself. For this reason, singers
      and all professional voice users about to undergo surgical treatment for snoring
      should be informed of this potential modification of the voice not only for
      clinical reasons but also for legal purposes.

PMID- 16886854
TI  - Sudden cochlear hearing loss as presenting symptom of arachnoid cyst of the
      posterior fossa.
AB  - Arachnoid cysts account for almost 1% of neoformations located in the
      cerebellopontine angle. The aetiopathogenesis is unknown. Arachnoid cysts of the
      cranial posterior fossa may produce symptoms typical of a tumour such as
      headache, dizziness, tinnitus and progressive sensorineural hearing loss.
      Management of these lesions is still controversial; if the arachnoid cyst is
      symptomatic, surgical treatment is usually recommended. The case is described of
      an adult female with sudden unilateral cochlear hearing loss as presenting
      symptom of an arachnoid cyst in the cranial posterior fossa.

PMID- 16886855
TI  - Extramedullary plasmacytoma of paranasal sinuses. A combined therapeutic
      strategy.
AB  - Extramedullary plasmacytoma of the head and neck region is a rare malignant
      tumour comprising approximately 3% of all plasma cell tumours. Approximately 80
      90% of extramedullary plasmacytomas involve the Mucosa-Associated Lymphoid Tissue
      of the upper airways, 75% of these involve the nasal and paranasal regions.
      Radiotherapy is considered the treatment of choice, surgery being limited to
      biopsy and to excision of residual disease. A case of extramedullary plasmacytoma
      of the nasal cavity and ethmoid sinus is reported, in which surgical excision is
      followed by complementary radiotherapy on the site of the tumour.

PMID- 16886856
TI  - Font adaptive word indexing of modern printed documents.
AB  - We propose an approach for the word-level indexing of modern printed documents
      which are difficult to recognize using current OCR engines. By means of word
      level indexing, it is possible to retrieve the position of words in a document,
      enabling queries involving proximity of terms. Web search engines implement this
      kind of indexing, allowing users to retrieve Web pages on the basis of their
      textual content. Nowadays, digital libraries hold collections of digitized
      documents that can be retrieved either by browsing the document images or relying
      on appropriate metadata assembled by domain experts. Word indexing tools would
      therefore increase the access to these collections. The proposed system is
      designed to index homogeneous document collections by automatically adapting to
      different languages and font styles without relying on OCR engines for character
      recognition. The approach is based on three main ideas: the use of Self
      Organizing Maps (SOM) to perform unsupervised character clustering, the
      definition of one suitable vector-based word representation whose size depends on
      the word aspect-ratio, and the run-time alignment of the query word with indexed
      words to deal with broken and touching characters. The most appropriate
      applications are for processing modern printed documents (17th to 19th centuries)
      where current OCR engines are less accurate. Our experimental analysis addresses
      six data sets containing documents ranging from books of the 17th century to
      contemporary journals.

PMID- 16886857
TI  - A binary linear programming formulation of the graph edit distance.
AB  - A binary linear programming formulation of the graph edit distance for
      unweighted, undirected graphs with vertex attributes is derived and applied to a
      graph recognition problem. A general formulation for editing graphs is used to
      derive a graph edit distance that is proven to be a metric, provided the cost
      function for individual edit operations is a metric. Then, a binary linear
      program is developed for computing this graph edit distance, and polynomial time
      methods for determining upper and lower bounds on the solution of the binary
      program are derived by applying solution methods for standard linear programming
      and the assignment problem. A recognition problem of comparing a sample input
      graph to a database of known prototype graphs in the context of a chemical
      information system is presented as an application of the new method. The costs
      associated with various edit operations are chosen by using a minimum normalized
      variance criterion applied to pairwise distances between nearest neighbors in the
      database of prototypes. The new metric is shown to perform quite well in
      comparison to existing metrics when applied to a database of chemical graphs.

PMID- 16886858
TI  - The distinctiveness of a curve in a parameterized neighborhood: extraction and
      applications.
AB  - A new feature of curves pertaining to the acceptance/rejection decision in curve
      detection is proposed. The feature measures a curve's distinctiveness in its
      neighborhood, which is modeled by a one-parameter family of curves. A
      computational framework based on the Hough transform for extracting the
      distinctiveness feature is elaborated and examples of feature extractors for the
      circle and the ellipse are given. It is shown that the proposed feature can be
      extracted efficiently and is effective in separating signals from false
      positives. Experimental results with circle and ellipse testing that strongly
      support the efficiency and effectiveness claims are obtained. The results further
      demonstrate that the proposed feature exhibits good noise resiliency.

PMID- 16886859
TI  - On weighting clustering.
AB  - Recent papers and patents in iterative unsupervised learning have emphasized a
      new trend in clustering. It basically consists of penalizing solutions via
      weights on the instance points, somehow making clustering move toward the hardest
      points to cluster. The motivations come principally from an analogy with powerful
      supervised classification methods known as boosting algorithms. However, interest
      in this analogy has so far been mainly borne out from experimental studies only.
      This paper is, to the best of our knowledge, the first attempt at its
      formalization. More precisely, we handle clustering as a constrained minimization
      of a Bregman divergence. Weight modifications rely on the local variations of the
      expected complete log-likelihoods. Theoretical results show benefits resembling
      those of boosting algorithms and bring modified (weighted) versions of clustering
      algorithms such as k-means, fuzzy c-means, Expectation Maximization (EM), and k
      harmonic means. Experiments are provided for all these algorithms, with a readily
      available code. They display the advantages that subtle data reweighting may
      bring to clustering.

PMID- 16886860
TI  - Learning nonlinear image manifolds by global alignment of local linear models.
AB  - Appearance-based methods, based on statistical models of the pixel values in an
      image (region) rather than geometrical object models, are increasingly popular in
      computer vision. In many applications, the number of degrees of freedom (DOF) in
      the image generating process is much lower than the number of pixels in the
      image. If there is a smooth function that maps the DOF to the pixel values, then
      the images are confined to a low-dimensional manifold embedded in the image
      space. We propose a method based on probabilistic mixtures of factor analyzers to
      (1) model the density of images sampled from such manifolds and (2) recover
      global parameterizations of the manifold. A globally nonlinear probabilistic two
      way mapping between coordinates on the manifold and images is obtained by
      combining several, locally valid, linear mappings. We propose a parameter
      estimation scheme that improves upon an existing scheme and experimentally
      compare the presented approach to self-organizing maps, generative topographic
      mapping, and mixtures of factor analyzers. In addition, we show that the approach
      also applies to finding mappings between different embeddings of the same
      manifold.

PMID- 16886861
TI  - Confidence-based active learning.
AB  - This paper proposes a new active learning approach, confidence-based active
      learning, for training a wide range of classifiers. This approach is based on
      identifying and annotating uncertain samples. The uncertainty value of each
      sample is measured by its conditional error. The approach takes advantage of
      current classifiers' probability preserving and ordering properties. It
      calibrates the output scores of classifiers to conditional error. Thus, it can
      estimate the uncertainty value for each input sample according to its output
      score from a classifier and select only samples with uncertainty value above a
      user-defined threshold. Even though we cannot guarantee the optimality of the
      proposed approach, we find it to provide good performance. Compared with existing
      methods, this approach is robust without additional computational effort. A new
      active learning method for support vector machines (SVMs) is implemented
      following this approach. A dynamic bin width allocation method is proposed to
      accurately estimate sample conditional error and this method adapts to the
      underlying probabilities. The effectiveness of the proposed approach is
      demonstrated using synthetic and real data sets and its performance is compared
      with the widely used least certain active learning method.

PMID- 16886863
TI  - Subclass discriminant analysis.
AB  - Over the years, many Discriminant Analysis (DA) algorithms have been proposed for
      the study of high-dimensional data in a large variety of problems. Each of these
      algorithms is tuned to a specific type of data distribution (that which best
      models the problem at hand). Unfortunately, in most problems the form of each
      class pdf is a priori unknown, and the selection of the DA algorithm that best
      fits our data is done over trial-and-error. Ideally, one would like to have a
      single formulation which can be used for most distribution types. This can be
      achieved by approximating the underlying distribution of each class with a
      mixture of Gaussians. In this approach, the major problem to be addressed is that
      of determining the optimal number of Gaussians per class, i.e., the number of
      subclasses. In this paper, two criteria able to find the most convenient division
      of each class into a set of subclasses are derived. Extensive experimental
      results are shown using five databases. Comparisons are given against Linear
      Discriminant Analysis (LDA), Direct LDA (DLDA), Heteroscedastic LDA (HLDA),
      Nonparametric DA (NDA), and Kernel-Based LDA (K-LDA). We show that our method is
      always the best or comparable to the best.

PMID- 16886862
TI  - Dynamical statistical shape priors for level set-based tracking.
AB  - In recent years, researchers have proposed introducing statistical shape
      knowledge into level set-based segmentation methods in order to cope with
      insufficient low-level information. While these priors were shown to drastically
      improve the segmentation of familiar objects, so far the focus has been on
      statistical shape priors which are static in time. Yet, in the context of
      tracking deformable objects, it is clear that certain silhouettes (such as those
      of a walking person) may become more or less likely over time. In this paper, we
      tackle the challenge of learning dynamical statistical models for implicitly
      represented shapes. We show how these can be integrated as dynamical shape priors
      in a Bayesian framework for level set-based image sequence segmentation. We
      assess the effect of such shape priors "with memory" on the tracking of familiar
      deformable objects in the presence of noise and occlusion. We show comparisons
      between dynamical and static shape priors, between models of pure deformation and
      joint models of deformation and transformation, and we quantitatively evaluate
      the segmentation accuracy as a function of the noise level and of the camera
      frame rate. Our experiments demonstrate that level set-based segmentation and
      tracking can be strongly improved by exploiting the temporal correlations among
      consecutive silhouettes which characterize deforming shapes.

PMID- 16886865
TI  - Shape registration in implicit spaces using information theory and free form
      deformations.
AB  - We present a novel, variational and statistical approach for shape registration.
      Shapes of interest are implicitly embedded in a higher-dimensional space of
      distance transforms. In this implicit embedding space, registration is formulated
      in a hierarchical manner: the Mutual Information criterion supports various
      transformation models and is optimized to perform global registration; then, a B
      spline-based Incremental Free Form Deformations (IFFD) model is used to minimize
      a Sum-of-Squared-Differences (SSD) measure and further recover a dense local
      nonrigid registration field. The key advantage of such framework is twofold: (1)
      it naturally deals with shapes of arbitrary dimension (2D, 3D, or higher) and
      arbitrary topology (multiple parts, closed/open) and (2) it preserves shape
      topology during local deformation and produces local registration fields that are
      smooth, continuous, and establish one-to-one correspondences. Its invariance to
      initial conditions is evaluated through empirical validation, and various hard
      2D/3D geometric shape registration examples are used to show its robustness to
      noise, severe occlusion, and missing parts. We demonstrate the power of the
      proposed framework using two applications: one for statistical modeling of
      anatomical structures, another for 3D face scan registration and expression
      tracking. We also compare the performance of our algorithm with that of several
      other well-known shape registration algorithms.

PMID- 16886864
TI  - Reflectance sharing: predicting appearance from a sparse set of images of a known
      shape.
AB  - Three-dimensional appearance models consisting of spatially varying reflectance
      functions defined on a known shape can be used in analysis-by-synthesis
      approaches to a number of visual tasks. The construction of these models requires
      the measurement of reflectance, and the problem of recovering spatially varying
      reflectance from images of known shape has drawn considerable interest. To date,
      existing methods rely on either: (1) low-dimensional (e.g., parametric)
      reflectance models, or (2) large data sets involving thousands of images (or
      more) per object. Appearance models based on the former have limited accuracy and
      generality since they require the selection of a specific reflectance model a
      priori, and while approaches based on the latter may be suitable for certain
      applications, they are generally too costly and cumbersome to be used for image
      analysis. We present an alternative approach that seeks to combine the benefits
      of existing methods by enabling the estimation of a nonparametric spatially
      varying reflectance function from a small number of images. We frame the problem
      as scattered-data interpolation in a mixed spatial and angular domain, and we
      present a theory demonstrating that the angular accuracy of a recovered
      reflectance function can be increased in exchange for a decrease in its spatial
      resolution. We also present a practical solution to this interpolation problem
      using a new representation of reflectance based on radial basis functions. This
      representation is evaluated experimentally by testing its ability to predict
      appearance under novel view and lighting conditions. Our results suggest that
      since reflectance typically varies slowly from point to point over much of an
      object's surface, we can often obtain a nonparametric reflectance function from a
      sparse set of images. In fact, in some cases, we can obtain reasonable results in
      the limiting case of only a single input image.

PMID- 16886866
TI  - Building models of animals from video.
AB  - This paper argues that tracking, object detection, and model building are all
      similar activities. We describe a fully automatic system that builds 2D
      articulated models known as pictorial structures from videos of animals. The
      learned model can be used to detect the animal in the original video--in this
      sense, the system can be viewed as a generalized tracker (one that is capable of
      modeling objects while tracking them). The learned model can be matched to a
      visual library; here, the system can be viewed as a video recognition algorithm.
      The learned model can also be used to detect the animal in novel images--in this
      case, the system can be seen as a method for learning models for object
      recognition. We find that we can significantly improve the pictorial structures
      by augmenting them with a discriminative texture model learned from a texture
      library. We develop a novel texture descriptor that outperforms the state-of-the
      art for animal textures. We demonstrate the entire system on real video sequences
      of three different animals. We show that we can automatically track and identify
      the given animal. We use the learned models to recognize animals from two data
      sets; images taken by professional photographers from the Corel collection, and
      assorted images from the Web returned by Google. We demonstrate quite good
      performance on both data sets. Comparing our results with simple baselines, we
      show that, for the Google set, we can detect, localize, and recover part
      articulations from a collection demonstrably hard for object recognition.

PMID- 16886867
TI  - A generic camera model and calibration method for conventional, wide-angle, and
      fish-eye lenses.
AB  - Fish-eye lenses are convenient in such applications where a very wide angle of
      view is needed, but their use for measurement purposes has been limited by the
      lack of an accurate, generic, and easy-to-use calibration procedure. We hence
      propose a generic camera model, which is suitable for fish-eye lens cameras as
      well as for conventional and wide-angle lens cameras, and a calibration method
      for estimating the parameters of the model. The achieved level of calibration
      accuracy is comparable to the previously reported state-of-the-art.

PMID- 16886869
TI  - Maximization of mutual information for offline Thai handwriting recognition.
AB  - This paper aims to improve the performance of an HMM-based offline Thai
      handwriting recognition system through discriminative training and the use of
      fine-tuned feature extraction methods. The discriminative training is implemented
      by maximizing the mutual information between the data and their classes. The
      feature extraction is based on our proposed block-based PCA and composite images,
      shown to be better at discriminating Thai confusable characters. We demonstrate
      significant improvements in recognition accuracies compared to the classifiers
      that are not discriminatively optimized.

PMID- 16886868
TI  - Table detection in online ink notes.
AB  - In documents, tables are important structured objects that present statistical
      and relational information. In this paper, we present a robust system which is
      capable of detecting tables from free style online ink notes and extracting their
      structure so that they can be further edited in multiple ways. First, the
      primative structure of tables, i.e., candidates for ruling lines and table
      bounding boxes, are detected among drawing strokes. Second, the logical structure
      of tables is determined by normalizing the table skeletons, identifying the
      skeleton structure, and extracting the cell contents. The detection process is
      similar to a decision tree so that invalid candidates can be ruled out quickly.
      Experimental results suggest that our system is robust and accurate in dealing
      with tables having complex structure or drawn under complex situations.

PMID- 16886871
TI  - Herpes simplex infection--Part II: Management of HSV infections.
AB  - Oral and perioral herpes simplex virus infections are commonly seen and managed
      by the dental practitioner. Many topical and oral antiviral agents are available
      in Israel. However, only a few regimens are based on solid evidence. The purpose
      of this study was to review the mode of action of antiviral agents and to present
      therapeutic regimens supported by randomized control trials.

PMID- 16886870
TI  - Affine-invariant geometric shape priors for region-based active contours.
AB  - We present a new way of constraining the evolution of a region-based active
      contour with respect to a reference shape. Minimizing a shape prior, defined as a
      distance between shape descriptors based on the Legendre moments of the
      characteristic function, leads to a geometric flow that can be used with benefits
      in a two-class segmentation application. The shape model includes intrinsic
      invariance with regard to pose and affine deformations.

PMID- 16886872
TI  - [Decision making of Hebrew University and Tel Aviv University Dental Schools
      graduates in every day dentistry--is there a difference?].
AB  - This study was designed to evaluate decision-making among Jerusalem Hebrew
      University and Tel Aviv University dental schools graduates in various
      restorative dentistry, endodontics and oral surgery issues. A survey was
      conducted among 52 dentists during a dental military convention. Most of the
      dentists stated they will not recommend of re-treatment of endodontic-treated
      tooth with asymptomatic peri-apical pathology that does not need further
      rehabilitation. The study reveals over treatment and over-medication in
      restorative and surgery decisions. More than half of the dentists decided to
      treat caries lesions that extend to the dentino enamel junction, in low and
      moderate caries risk patients. More Hebrew University graduates than Tel Aviv
      University graduates recommend of removal of asymptomatic horizontal fully
      impacted mandibular third molar and disease-free maxillary third molar
      antagonist. Most of Tel Aviv graduates routinely prescribe antibiotic coverage
      after complicated tooth extraction. This study supports the need for continuing
      education on daily performed dental procedures.

PMID- 16886873
TI  - [Vertical root fractures in endodontically treated teeth--Part II: Etiology and
      prevention].
AB  - The etiologic factors for vertical fractures in endodontically treated teeth are
      predisposing factors, such as loss of tooth material, anatomy of the susceptible
      teeth, moisture loss, previous dentinal cracks, and loss of bone support; and
      iatrogenic factors, such as excessive removal of radicular dentin as a result of
      endodontic and prosthetic procedures and improper selection of dowels.
      Identification of susceptible teeth and roots, proper selection and cementation
      of dowels, and avoidance of excessive force during condensation of gutta percha
      and in removal of tooth structure during endodontic and prosthetic procedures,
      are all measures that can be taken to prevent root fractures.

PMID- 16886874
TI  - [Dental trauma protocol--treatment of avulsion and luxation injury].
AB  - The goal of this protocol is to provide clear instructions which simplify the
      process of decision making and treatment of Luxation and Avulsion. In teeth with
      a closed apex, one should perform root canal therapy at the second appointment in
      teeth with injuries of luxation and avulsion (except for injuries of subluxation
      and concussion). The tooth should be reimplanted at site of accident if it
      possible. For avulsed teeth, the preferred storage medium is milk. One should
      condition the roots of teeth which have been avulsed. In teeth which have not
      finished development, the preferred treatment is to allow the continued
      development of the root.

PMID- 16886877
TI  - "Special Olympics": a triumph of human will power.

PMID- 16886878
TI  - "Economies".

PMID- 16886875
TI  - [Bisphosphonate associated osteonecrosis of the jaws--the role of the dentist in
      prevention and early diagnosis].
AB  - During the past few years numerous cases of osteonecrosis of the jaws in patients
      receiving bisphosphonate therapy were published in the literature. In most cases,
      the osteonecrosis was diagnosed following dento-alveolar surgery, especially
      following extraction of teeth. To date, no efficient therapy is available and
      most efforts are geared towards prevention. The propose of the present review is
      to inform the Israeli dental community about osteonecrosis of the jaws in
      patients receiving bisphosphonate therapy and to suggest strategies for
      prevention.

PMID- 16886879
TI  - Regulating the "little clinic".

PMID- 16886880
TI  - Secondhand smoke and indoor public spaces in Paducah, Kentucky.
AB  - INTRODUCTION: Secondhand smoke (SHS) is the third leading cause of preventable
      death in the United States. It is responsible for an estimated 3,000 lung cancer
      deaths annually in never-smokers in the US. It also accounts for over 35,000
      deaths annually from coronary heart disease in never-smokers. It increases the
      number and severity of asthmatic attacks in over 300,000 asthmatic children each
      year, and is associated with Sudden Infant Death Syndrome and middle ear
      infections, in addition to other illnesses in children. The purpose of this study
      was to examine indoor air quality in a sample of hospitality venues in Paducah,
      Kentucky. The relation between indoor air pollution and the presence of on
      premises smoking was assessed. METHODS: A Personal Aerosol Monitor was used to
      sample and record the levels of respirable suspended particles in the air. The
      SidePak uses a built-in sampling pump that draws air through the device and the
      particulate matter in the air scatters the light from a laser. Based on this
      light scattering, the device determines to assess the real-time concentration of
      particles smaller than 2.5 microm in micrograms per cubic meter, or PM2.5.
      RESULTS: The average PM2.5 concentration in the eleven locations sampled in
      Paducah, Kentucky, was 177 microg/m3. The average fine particle pollution level
      in the non-smoking sections tested was 87 microg/m3, which is 29 times higher
      than the average fine particle pollution level in smoke-free air or 6 times
      higher than outdoor air in Paducah. The average PM2.5 level across all nine
      smoking-permitted hospitality locations sampled in Paducah was 200 microg/m3. For
      a full-time employee in the venues sampled in this study, the average annual
      PM2.5 exposure would be 46 microg/m3 (assuming exposure to 200 microg/m3 on the
      job, exposure to zero particles off the job, and a 40-hour work week). The EPA
      average annual PM2.5 limit is exceeded by 3.1 times due solely to occupational
      exposure. Of the ten locations visited that permit indoor smoking, the air
      monitoring was done in the non-smoking section of six of them. These locations
      included five restaurants and one public government office. The average fine
      particle pollution level in these non-smoking sections was 87 microg/m3, which is
      29 times higher than the average fine particle pollution level in smoke-free air
      or 6 times higher than outdoor air in Paducah. It is also interesting to note
      that the average fine particle pollution level in the smoking section of one
      restaurant was actually less than the average fine particle pollution level in
      the "no smoking" section of two other restaurants. CONCLUSIONS: The effects of
      secondhand smoke are substantial and rapid, explaining the relatively large
      health risks associated with secondhand smoke exposure that have been reported in
      epidemiological studies. This study shows that physically separating smokers and
      non-smokers is not an effective way to protect non-smoking patrons from tobacco
      smoke pollution. "No smoking" sections provided protection to nonsmokers that can
      be characterized as trivial at best. In fact, patrons in Paducah cannot be
      certain that their exposure will not be higher in the "no smoking" sections of
      certain venues when compared to the smoking sections of other venues. It is
      imperative that physicians and other healthcare providers actively and
      aggressively lobby local policymakers to pass regulatory and/or public health
      ordinances, which have been demonstrated to be effective in controlling exposure
      to secondhand smoke.

PMID- 16886881
TI  - Obstructive sleep apnea in a patient with basal cell nevus syndrome.
AB  - A 20-year-old male with basal cell nevus syndrome (also known as Gorlin-Goltz
      Syndrome) was evaluated for snoring, daytime hypersomnolence, and poorly
      controlled hypertension. Nocturnal polysomnography confirmed obstructive sleep
      apnea syndrome with correction of symptoms with nasal bilevel positive pressure
      ventilation. Assessment for sleep disordered breathing is imperative in ongoing
      care for patients with this disorder.

PMID- 16886882
TI  - Serum hs-CRP as a useful marker for predicting the efficacy of lumbar epidural
      steroid injections on pain relief in patients with lumbar disc herniations.
AB  - INTRODUCTION: We examined systemic inflammatory serum markers and pain responses
      to image-guided lumbar epidural steroid injections (LESI) both before and after
      LESI in patients with lumbar disc herniations with various pathological
      intervertebral disc changes. METHODS: Sixty male patients were scheduled for LESI
      every two weeks for three injections. Prior to injection therapy the following
      laboratory tests were performed: a complete blood count (CBC), high-sensitivity C
      reactive protein (hs-CRP), and an erythrocyte sedimentation rate (ESR). Five
      groups of fifteen patients each were classified according to MRI observation: I)
      control group, II) disc protrusion, III) disc prolapse, IV) disc extrusion, and
      V) sequestered disc herniation. LESI were scheduled two weeks apart and were done
      with fluoroscopy using 40 mg of triamcinolone with 5 ml of preservative-free
      lidocaine. All patients returned 6 weeks following their initial injection and
      repeat hs-CRP assays were obtained. RESULTS: No patient in this study had an
      abnormal CBC or ESR. No patient in the control group had an elevated hs-CRP. The
      percentage and number of patients in each experimental group with elevated hs-CRP
      levels were: II) 0% (0/15), III) 20% (3/15), IV) 80% (12/15), and V) 73% (11/15).
      LESI was more efficacious in the two contained disc herniation groups (II and
      III). It was found that the higher the hs-CRP levels prior to LESI therapy, the
      less improvement in pain scores following LESI. DISCUSSION: The results of this
      study suggest that elevated hs-CRP levels may be useful for objectively
      evaluating and predicting responses to LESI in those patients with lumbar disc
      pathology with lower extremity radiculitis.

PMID- 16886883
TI  - Physicians and hospitals.

PMID- 16886884
TI  - There is a plan.

PMID- 16886885
TI  - Continuous quality improvement initiatives in the cardiac catheterization
      laboratory: can we have our cake and eat it too?

PMID- 16886886
TI  - Polypharmacy with oral antidiabetic agents: an indicator of poor glycemic
      control.
AB  - OBJECTIVE: To evaluate antidiabetic drug treatment patterns and glycemic control
      among patients diagnosed with type 2 diabetes mellitus. STUDY DESIGN:
      Retrospective study using the automated databases of a 200 000-member HMO.
      METHODS: The study population consisted of patients > or =18 years of age with
      documented type 2 diabetes mellitus from January 1, 2002, through December 31,
      2002. We determined the proportion of patients who had optimal glycemic control
      (glycosylated hemoglobin <7%) during the 6 months after the initial documentation
      of diabetes during calendar year 2002 (index date). RESULTS: Of the 4282 patients
      who met the inclusion criteria, 1050 (25%) received 1 oral agent, 486 (11%)
      received 2 oral agents, 56 (1%) received > or =3 oral agents, 84 (2%) received
      insulin and an oral agent, and 107 (2%) received insulin exclusively within 90
      days after the index date. Among the 1075 patients receiving antidiabetic drug
      therapy who had a laboratory test result documented, 414 (39%) had optimal
      glycemic control. Optimal control was most frequent among patients receiving 1
      oral agent (47%) and least frequent among patients receiving > or =3 oral agents
      (13%) (P <.01). Patients with a prior history of suboptimal glycemic control were
      less likely to have optimal glycemic control. CONCLUSIONS: Multiple oral
      antidiabetic agents may serve as a marker for more severe, uncontrolled diabetes.
      The vast majority of patients treated with multiple oral antidiabetic agents had
      suboptimal glycemic control, suggesting a need for intensified efforts to treat
      this particular group of patients to recommended goal levels.

PMID- 16886887
TI  - Economic and clinical outcomes of a physician-led continuous quality improvement
      intervention in the delivery of percutaneous coronary intervention.
AB  - OBJECTIVE: To compare clinical and economic outcomes associated with percutaneous
      coronary intervention (PCI) in cohorts before and after continuous quality
      improvement (CQI) was instituted. STUDY DESIGN: Observational study. METHODS:
      Clinical, angiographic, procedural, and outcome data on 1441 pre-CQI and 1760
      post-CQI PCIs (performed in 1997 and 1998, respectively) were derived from an
      institutional PCI registry. Administrative data were used to estimate total
      procedural and postprocedural costs and length of stay (LOS). Logistic and
      generalized linear modeling was used to adjust in-hospital clinical and economic
      outcomes, respectively, for differences in patient characteristics. RESULTS: The
      2 cohorts were similar in terms of age, sex, and rate of diabetes. Post-CQI
      patients more often received intracoronary stents, had urgent PCIs, had a history
      of prior PCI, and received glycoprotein IIb/IIIa inhibitors. Procedural success
      without in-hospital complications occurred in 90% of both cohorts and did not
      differ statistically in adjusted analyses. Compared with patients treated pre
      CQI, those treated post-CQI had a reduced adjusted odds ratio for in-hospital
      death or any myocardial infarction (odds ratio = 0.66; 95% confidence interval =
      0.46, 0.95). Models predicted a mean postprocedural LOS difference of 0.8 days
      (2.8 days pre-CQI vs 2.0 days post-CQI; P <.001) and an average post-CQI cost
      savings of $5430 (P <.001). CONCLUSION: Physician-led, multidisciplinary practice
      management efforts were successful at significantly reducing PCI-related costs in
      an era of rapid technological advances while maintaining and perhaps improving
      quality of care.

PMID- 16886888
TI  - Frequency of follow-up care for adult and pediatric patients during initiation of
      antidepressant therapy.
AB  - OBJECTIVES: To measure the timing and frequency of follow-up care during the
      initiation phase of antidepressant therapy, and to compare the typical pattern of
      care with current product guidelines. STUDY DESIGN: Retrospective cohort study.
      METHODS: The study included 84514 adult and pediatric patients who started a new
      course of antidepressant therapy for any indication between July 2001 and
      September 2003. Patients were members of a large managed care organization in the
      northeastern United States. Ambulatory visits during the first 12 weeks of
      treatment were identified using medical claims data. Outcome measures were time
      to first follow-up visit, frequency of follow-up visits, and percentage of
      patients receiving recommended levels of care. RESULTS: During the first 4 weeks
      of treatment with antidepressants, only 55.0% of patients saw a healthcare
      provider for any purpose, and only 17.7% saw a provider for mental healthcare.
      Ambulatory visit rates during the first 4, 8, and 12 weeks were significantly
      lower than the minimum levels recommended in product labeling (P <.0001). Only
      14.9% of patients received the Food and Drug Administration-recommended level of
      follow-up care during the first 4 weeks, 18.1% at 8 weeks, and 22.6% at 12 weeks.
      CONCLUSIONS: Adults and children who begin a new course of antidepressant therapy
      tend to receive far less monitoring than is recommended in current product
      labeling. Given safety concerns during the initiation phase, earlier and more
      frequent follow-up care appears desirable. Further research is needed to identify
      the most cost-effective schedule of care.

PMID- 16886889
TI  - The effectiveness of a care coordination home telehealth program for veterans
      with diabetes mellitus: a 2-year follow-up.
AB  - OBJECTIVES: To assess healthcare use among veterans with diabetes mellitus (DM)
      enrolled in a Department of Veterans Affairs (VA) Care Coordination Home
      Telehealth (CCHT) program during 24 months and to contrast this utilization with
      the service use of a comparison group of veterans with DM not enrolled in the
      program. STUDY DESIGN: Two-year, retrospective, concurrent matched cohort study
      design. METHODS: The VA CCHT program included older veterans with type 2 DM at
      high risk for multiple VA inpatient and outpatient visits. Healthcare utilization
      (hospitalizations, length of stay, and outpatient visits by type) was assessed at
      baseline and at 24 months after intervention for the treatment (n = 400) and
      comparison (n = 400) groups. Propensity scores were used to improve the balance
      between the treatment and comparison groups. A difference-in-differences approach
      was used to control for selection bias and for intervening time factors. RESULTS:
      Two years after enrollment, the treatment group exhibited a statistically
      significant reduction in the likelihood of all-cause and DM-related
      hospitalizations. In a subgroup analysis in which we controlled for patients'
      baseline glycosylated hemoglobin levels, the treatment group had a lower
      likelihood of having any care coordinator-initiated primary care clinic visits
      (in which the care coordinator initiated referral to primary care based on health
      information received from patients' CCHT technology). CONCLUSION: After
      controlling for selection bias and for intervening time factors, the VA CCHT
      program reduced avoidable healthcare services for DM (such as hospitalizations)
      and reduced care coordinator-initiated primary care clinic visits.

PMID- 16886890
TI  - Development and validation of a medication intensity scale derived from
      computerized pharmacy data that predicts emergency hospital utilization for
      persistent asthma.
AB  - OBJECTIVE: To validate a risk stratification scheme using computerized pharmacy
      data to predict emergency hospital utilization for persistent asthma. STUDY
      DESIGN: Retrospective cohort. METHODS: The development sample consisted of 1079
      HMO members aged 18 to 56 years with persistent asthma. The scale used medication
      cut-points as predictors for next-year emergency hospital utilization in a
      stepwise logistic regression model. Prediction properties were evaluated in a
      validation sample of 24 370 patients aged 18 to 56 years in a separate persistent
      asthma database. RESULTS: Increasing use of beta-agonists (odds ratio [OR] of 2.2
      for 5-13 vs 0-4 canisters; OR of 2.4 for >13 vs 5-13 canisters) and oral
      corticosteroids (OR of 2.6 for >2 vs 0-2 dispensing events) in the first year
      independently predicted emergency hospital utilization in the second year.
      Assigning 1 point for exceeding each of the above 3 medication thresholds led to
      a 4-level medication intensity scale that was significantly (P <.0001) related to
      validated measures of asthma symptom severity, asthma control, and asthma quality
      of life in the development sample. In the validation sample, this scheme
      identified a high-risk group that was 6 times more likely than the low-risk group
      to require subsequent emergency hospital care, with overall sensitivity of 65%
      and specificity of 54%. This scale did not perform as well as a scale based on
      both baseline emergency hospital care and pharmacy data. CONCLUSION: This simple
      risk stratification scheme can be used for populations with persistent asthma for
      whom computerized pharmacy data, but not computerized prior utilization data, are
      available.

PMID- 16886892
TI  - Gene signature of breast cancer cell lines treated with lycopene.
AB  - Among the micronutrients studied in relation between nutrition and cancer,
      lycopene appears to be a breast cancer preventive phytochemical candidate found
      in raw tomatoes and tomato-derived products. In order to investigate the
      responsiveness of breast cancer genes to lycopene and to better understand the
      molecular mechanisms underlying the effects of lycopene, we used an
      oligonucleotide microarray approach. Human breast cancer cell lines (MCF-7 and
      MDA-MB-231) and a fibrocystic breast cell line (MCF-10a) were either exposed or
      not exposed to 10 microM lycopene for 48 h. Microarrays comprising 202 genes were
      used to identify genes responsive to lycopene supplementation. Hierarchical
      clustering revealed a cell line-specific lycopene modulation of breast cells.
      Based on the observed results, lycopene seems to exert regulation on apoptosis,
      cell cycle and DNA repair mechanisms according to estrogen and retinoic acid
      receptor cell status.

PMID- 16886893
TI  - Arylamine N-acetyltransferase gene polymorphisms: markers for atopic asthma,
      serum IgE and blood eosinophil counts.
AB  - INTRODUCTION: Polymorphisms in N-acetyltransferase 2 (NAT2), present on
      chromosome 8p22, are responsible for the N-acetylation variants, which segregate
      human populations into rapid, intermediate and slow acetylators and influence the
      susceptibility towards atopic disorders. We have undertaken a study of the North
      Indian population to screen for various NAT2 polymorphisms and to investigate
      their association with atopic asthma and related phenotypes. METHODS: First, to
      establish linkage of the 8p22 region with asthma, 158 families were recruited
      from North India. Next, a total of 219 unrelated atopic asthmatics and 210
      unrelated healthy controls were recruited for case-control disease association
      studies. RESULTS: A suggestive linkage was observed with microsatellite marker
      D8S549, 2.6 MB upstream of NAT2. By sequencing the DNA of 40 individuals, the
      T111C, G191A, A434C and C759T single nucleotide polymorphisms (SNPs) in NAT2 were
      found to be nonpolymorphic in our population and a pattern of strong linkage
      disequilibrium was observed among the T341C, C481T and A803G polymorphisms. Thus,
      a total of 429 individuals were genotyped for the C481T and unlinked C282T
      polymorphisms. The C481T polymorphism was found to be significantly associated
      with asthma in our case-control studies at the genotype level (Armitage p =
      0.00027). C481T also showed a marginal association with serum total IgE (TsIgE)
      (p = 0.022). Furthermore, percent blood eosinophil counts were found to be
      significantly higher in patients carrying the 481T allele (p = 0.0037).
      Significant association was also detected with respect to the C282T polymorphism
      and TsIgE (p = 0.008). Moreover, C_T was found to be an important risk (p =
      0.001), while C_C was a major protective haplotype (p = 0.0005). The associations
      remained significant after Bonferroni correction for multiple testing.
      CONCLUSION: In summary, the genetic variants of the NAT2 gene do not seem to
      affect asthma alone, but act as modulators of asthma-related traits, such as
      serum IgE and blood eosinophil counts, and therefore could serve as genetic
      markers.

PMID- 16886894
TI  - IL-1B and IL-1RN gene polymorphisms in rheumatoid arthritis: relationship with
      protein plasma levels and response to therapy.
AB  - OBJECTIVES: To analyze the association of interleukin (IL-1) gene polymorphisms
      with susceptibility to, and severity of, rheumatoid arthritis (RA) patients,
      comparing them with the genotype distribution in healthy controls. Also, to
      assess the influence of IL1-B and IL1RN gene polymorphism on IL-1beta/IL-1Ra
      plasma levels and response to therapy. PATIENTS AND METHODS: We tested the
      allelic distribution of IL-1B (-511 and +3953) and IL-1RN (variable number of
      tandem repeats) gene polymorphism in 126 RA patients and 178 healthy blood donors
      (HBDs). The patients were categorized into two subgroups in relation to the
      response to methotrexate (MTX) therapy. Group A included 70 RA patients in stable
      partial remission after 6 months of MTX treatment (MTX-R). Group B included 56 RA
      patients with active disease despite MTX therapy. This group received antitumor
      necrosis factor (TNF) biological drugs and were defined MTX-nonresponders (MTX
      NR). RESULTS: None of the two IL-1B (-511 and +3953) gene polymorphisms were
      significantly different in frequency between RA patients and healthy controls. We
      observed an increased frequency of the rare allele IL1RN*3 in RA patients with
      active disease, not responding to MTX therapy (MTX-NR) (4.5%) vs MTX-R (3.6%) and
      healthy controls (0.8%). Interestingly, RA patients whose genotypes included the
      IL1RN*long allele (haplotype long-C-T) showed the worse response to MTX. HBDs
      harboring the IL1RN*2/2 genotype showed significantly lower levels of plasma IL1
      Ra, but comparable levels of IL-1beta with regard to subjects with the presence
      of the IL1RN* long allele. Furthermore, the presence of the TT IL-1B +3953
      genotype was associated with lower plasma levels of IL1-Ra, both in HBDs and in
      RA patients. Carriers of the IL1RN*2 allele responded better to infliximab
      therapy. CONCLUSIONS: The results of this study provide evidence of an
      association between the IL1RN*long allele and RA, the strongest association being
      observed in RA patients with an aggressive disease resistant to MTX treatment.

PMID- 16886895
TI  - Genetic predisposition of responsiveness to therapy for chronic hepatitis C.
AB  - BACKGROUND: A combination of interferon-alpha (IFN-alpha) and ribavirin has been
      the choice for treating chronic hepatitis C (CHC) patients. It achieves an
      overall sustained response rate of approximately 50%; however, the treatment
      takes 6-12 months and often brings significant adverse reactions to some
      patients. It would therefore be beneficial to include a pretreatment evaluation
      in order to maximize the efficacy. In addition to viral genotypes, we hypothesize
      that patient genotypes might also be useful for the prediction of treatment
      response. METHODS: We retrospectively analyzed the genetic differences of CHC
      patients that are associated with IFN/ribavirin responses. The DNA polymorphisms
      among 195 sustained responders and 122 nonresponders of CHC patients of Taiwanese
      origin were compared. Statistical and algorithmic methods were used to select the
      genes associated with drug response and single nucleotide polymorphisms (SNPs)
      that permitted the construction of a predictive model. RESULTS: Association
      studies and haplotype reconstruction revealed selection of seven genes: adenosine
      deaminase, RNA-specific (ADAR), caspase 5, apoptosis-related cysteine peptidase
      (CASP5), fibroblast growth factor 1 (FGF1), interferon consensus sequence binding
      protein 1 (ICSBP1), interferon-induced protein 44 (IFI44), transporter 2, ATP
      binding cassette, subfamily B (TAP2) and transforming growth factor, beta
      receptor associated protein 1 (TGFBRAP1) for the responsiveness trait. Based on
      confirmed linkage disequilibrium block in the population, a minimal set of 26
      SNPs in the seven selected genes was inferred. To predict treatment outcome, a
      multiple logistic regression model was constructed using susceptible genotypes of
      SNPs. The performance of the resultant model had a sensitivity of 68.2% and
      specificity of 60.7% on 317 CHC patients treated with IFN-combined therapy. In
      addition, a prediction model with both the host genetic and viral genotype
      information was also constructed which enhanced the performance with a
      sensitivity of 80.7% and specificity of 67.2%. CONCLUSIONS: A genetic model was
      constructed to predict outcomes of the combination therapy in CHC patients with
      high sensitivity and specificity. Results also provide a possible process of
      selecting targets for predicting treatment outcomes and the basis for developing
      pharmacogenetic tests.

PMID- 16886896
TI  - Glutathione S-transferases mu 1, theta 1, pi 1, alpha 1 and mu 3 genetic
      polymorphisms and the risk of colorectal and gastric cancers in humans.
AB  - INTRODUCTION: Glutathione S-transferases (GSTs) are considered to be cancer
      susceptibility genes as they play a role in the detoxification of carcinogenic
      species. This study aimed to elucidate the influence of several GST polymorphisms
      on colorectal and gastric cancer risk. PATIENTS AND METHODS: GST mu1 (GSTM1),
      theta1 (GSTT1), pi1 (GSTP1), alpha1 (GSTA1) and mu3 (GSTM3) genotypes were
      determined in 144 colorectal cancer patients, 98 gastric cancer patients and 329
      healthy control individuals. RESULTS: Colorectal cancer: the risk is greater for
      carriers of the GSTM1 null genotype (odds ratio [OR] = 1.91, 95% confidence
      interval [CI] = 1.25-2.91), for carriers of the GSTT1 null genotype (OR = 3.62,
      95% CI = 2.34-5.62), and for simultaneous carriers of both GSTM1 and GSTT1 null
      genotypes (OR = 4.98, 95% CI = 2.77-9.00). Carriers of the GSTP1 104 Val/Val
      genotype are at a lower risk (OR = 0.31, 95% CI = 0.09-0.88). Among carriers of
      the GSTP1 Ile/Ile genotype, smoking increases the risk compared with nonsmoking
      (OR = 2.35, 95% CI = 1.11-4.99). Gastric cancer: the risk is greater for carriers
      of the GSTT1 null genotype (OR = 2.58, 95% CI = 1.53-4.36) and for simultaneous
      carriers of both GSTM1 and GSTT1 null genotypes (OR = 3.32, 95% CI = 1.62-6.77).
      Carriers of the GSTP1 104 Val/Val genotype are at a lower risk (OR = 0.20, 95% CI
      = 0.02-0.86). DISCUSSION: The GSTT1 null genotype, particularly if it is
      associated with the GSTM1 null genotype, greatly increases the risk for
      colorectal and gastric cancers. The GSTP1 104 Val/Val genotype may protect from
      both malignant tumors. CONCLUSION: This study indicates that GST polymorphisms,
      in particular the GSTM1/GSTT1 double-null haplotype, can be considered low
      penetrance genes for gastrointestinal cancer.

PMID- 16886897
TI  - Pharmacogenetics of alkylator-associated acute myeloid leukemia.
AB  - Therapy-related acute myeloid leukemia (t-AML) is a lethal late complication of
      alkylator chemotherapy. The genetic basis of susceptibility to t-AML is poorly
      understood. Both t-AML and de novo AML are complex genetic diseases, requiring
      cooperating mutations in interacting pathways for disease initiation and
      progression. Germline variants of these 'leukemia pathway' genes may cooperate
      with somatic mutations to induce both de novo and therapy-related AML. Several
      cancer susceptibility syndromes have been identified that cause an inherited
      predisposition to de novo and t-AML. The genes responsible for these syndromes
      are also somatically mutated in sporadic AML. We reason that germline
      polymorphism in any gene somatically mutated in AML could contribute to t-AML
      risk in the general population. Identification of these susceptibility alleles
      should help clinicians develop tailored therapies that reduce the relative risk
      of t-AML.

PMID- 16886898
TI  - Genetic association studies in epilepsy pharmacogenomics: lessons learnt and
      potential applications.
AB  - Although epilepsy is one of the most common neurological disorders and genetic
      factors are well known to play a role in response to antiepileptic drug (AED)
      treatment, the study of the pharmacogenetics of epilepsy has received relatively
      little attention and has not resulted in clinical applications to date. Our
      improved understanding of the pathogenesis of epilepsy and the mechanism of
      action of AEDs, together with recent advances in genetics and decreasing
      genotyping costs, have now paved the way for a more systematic application of
      pharmacogenetics in the field of epilepsy. It is hoped that the resulting
      knowledge will lead to a more rational treatment of epilepsy, development of more
      efficacious AEDs, and facilitation of clinical trials of new AEDs. However, there
      are formidable practical, methodological and theoretical hurdles to overcome
      before pharmacogenomic information will have any major utility in the clinical
      setting. Here, we discuss the evidence for a genetic contribution to AED
      response, review current knowledge in epilepsy pharmacogenetics and discuss
      potential future avenues with their implications, both for the clinical treatment
      of epilepsy and new AED development.

PMID- 16886899
TI  - Epigenetics: an emerging technology in the diagnosis and treatment of cancer.
AB  - Transcriptional silencing resulting from changes in epigenetic regulation of gene
      expression is the most frequent mechanism by which tumor suppressor genes are
      inactivated in human cancer. Genes participating in numerous functional groups
      and pathways leading to malignancy are subject to aberrant CpG methylation, with
      associated downregulation of expression, in human carcinogenesis. Methylation
      profiling can identify distinct subtypes of common human cancers and may have
      utility in predicting clinical phenotypes in individual patients, including
      sensitivity to chemotherapeutic agents. Hypomethylating agents have clinical
      activity in some hematological malignancies, and there is accumulating evidence
      correlating clinical response with demethylation and concomitant reactivation of
      expression of specific target genes. Epigenetic analysis is likely to have an
      increasingly important part to play in the diagnosis, prognostic assessment and
      treatment of malignant disease.

PMID- 16886900
TI  - The application of CD antigen proteomics to pharmacogenomics.
AB  - The advent of multiplexing technologies has raised the possibility that disease
      states can be defined using discrete genomic and proteomic patterns or
      signatures. However, this emerging area has been limited by the 'content
      problem', arising from the uncertainty of which molecules to focus on. The human
      cluster of differentiation (CD) antigens are expressed on cells of the human
      immune system (leukocytes) and on other cell types. These heterogeneous molecules
      perform a host of roles essential to immune function and to the physiology of
      other lineages. The 339 defined CD antigens and their, as yet, undefined
      counterparts constitute key components of the expressed human cell surface
      proteome. We propose that CD antigen expression patterns will form the basis of a
      rational, discrete and generalized diagnostic and prognostic system. Furthermore,
      disease-specific CD antigen proteomic signatures are likely to be more robust
      than corresponding genomic signatures and will also help to identify molecular
      targets for therapeutic intervention.

PMID- 16886901
TI  - Process map proposal for the validation of genomic biomarkers.
AB  - How can we encourage the application of novel genomic biomarkers in drug
      development? A major step in this direction would be a consensus on how to
      interpret results from measurements of these biomarkers in regulatory
      submissions. A transparent process for genomic biomarker validation would be of
      value both for the pharmaceutical industry as well as for regulatory agencies
      associated with it. A discussion on process map proposals for genomic biomarker
      validation can help with drafting of guidance documents for this process.

PMID- 16886902
TI  - Cost-effectiveness of pharmacogenomics in clinical practice: a case study of
      thiopurine methyltransferase genotyping in acute lymphoblastic leukemia in
      Europe.
AB  - Only a few studies have addressed the cost-effectiveness of pharmacogenetics
      interventions in healthcare. Lack of health economics data on aspects of
      pharmacogenetics is perceived as one of the barriers hindering its implementation
      for improving drug safety. Thus, a recent Institute for Prospective Technological
      Studies (IPTS) study, entitled 'Pharmacogenetics and pharmacogenomics: state-of
      the-art and potential socio-economic impact in the EU' included an explorative
      cost-effectiveness review for a pharmacogenetic treatment strategy compared with
      traditional medical practice. The selected case study examined the cost
      effectiveness of thiopurine methyltransferase (TMPT) genotyping prior to
      thiopurine treatment in children with acute lymphoblastic leukemia (ALL).
      Information for the cost-effectiveness model parameters was collected from
      literature surveys and interviews with experts from four European countries
      (Germany, Ireland, the Netherlands and the UK). The model has established that
      TPMT testing in ALL patients has a favorable cost-effectiveness ratio. This
      conclusion was based on parameters collected for TPMT genotyping costs, estimates
      for frequency of TMPT deficiency, rates of thiopurine-mediated myelosuppression
      in TPMT-deficient individuals, and myelosuppression-related hospitalization costs
      in each of the four countries studied. The mean calculated cost per life-year
      gained by TPMT genotyping in ALL patients in the four study countries was euro
      2100 (or euro 4800 after 3% discount) based on genotyping costs of euro 150 per
      patient. Cost per life-year gained is expected to further improve following the
      introduction of the wider use of TMPT genotyping and the availability of lower
      cost genotyping methods. Our analysis indicates that TPMT genotyping should be
      seriously considered as an integral part of healthcare prior to the initiation of
      therapy with thiopurine drugs.

PMID- 16886903
TI  - Gene Express Inc.
AB  - Gene Express, Inc. is a technology-licensing company and provider of Standardized
      Reverse Transcription Polymerase Chain Reaction (StaRT-PCR) services. Designed by
      and for clinical researchers involved in pharmaceutical, biomarker and molecular
      diagnostic product development, StaRT-PCR is a unique quantitative and
      standardized multigene expression measurement platform. StaRT-PCR meets all of
      the performance characteristics defined by the US FDA as required to support
      regulatory submissions [101,102] , and by the Clinical Laboratory Improvement Act
      of 1988 (CLIA) as necessary to support diagnostic testing [1] . A standardized
      mixture of internal standards (SMIS), manufactured in bulk, provides integrated
      quality control wherein each native template target gene is measured relative to
      a competitive template internal standard. Bulk production enables the compilation
      of a comprehensive standardized database from across multiple experiments, across
      collaborating laboratories and across the entire clinical development lifecycle
      of a given compound or diagnostic product. For the first time, all these data are
      able to be directly compared. Access to such a database can dramatically shorten
      the time from investigational new drug (IND) to new drug application (NDA), or
      save time and money by hastening a substantiated 'no-go' decision. High
      throughput StaRT-PCR is conducted at the company's automated Standardized
      Expression Measurement (SEM) Center. Currently optimized for detection on a
      microcapillary electrophoretic platform, StaRT-PCR products also may be analyzed
      on microarray, high-performance liquid chromatography (HPLC), or matrix-assisted
      laser desorption/ionization time-of-flight (MALDI-TOF) platforms. SEM Center
      services deliver standardized genomic data--data that will accelerate the
      application of pharmacogenomic technology to new drug and diagnostic test
      development and facilitate personalized medicine.

PMID- 16886904
TI  - Stem cells and chronic lung disease.
AB  - Stem cells have been shown to contribute to the repair and regeneration of
      injured lungs. These stem cells are resident in specific protected niches in the
      lung, or they can be mobilized from the bone marrow and recruited from the
      circulation in the setting of severe injury. Normal repair of the airway involves
      regeneration of the airway epithelium by stem cells in both the proximal airway
      and distal airspace, whereas aberrant repair of the lung may result from stem
      cells that lead to fibrosis. The stem cell niche in the lung is probably critical
      in determining whether "good" or "bad" stem cells are involved in local repair,
      and therefore whether fibrosis predominates. There is much excitement about the
      possibility of harnessing stem cells for repair and regeneration of the lungs.
      This review highlights current knowledge of this area and identifies gaps in our
      understanding of this complicated process.

PMID- 16886905
TI  - A human monoclonal antibody cocktail as a novel component of rabies postexposure
      prophylaxis.
AB  - The currently recommended treatment for individuals exposed to rabies virus is
      the combined administration of rabies vaccine and rabies immune globulin (RIG).
      This review sets out the criteria used to guide development of a cocktail of
      human monoclonal antibodies as a replacement for RIG. Using this process as a
      model, the general requirements for development of safe and efficacious
      monoclonal antibody alternatives to currently used polyclonal serum products are
      discussed.

PMID- 16886906
TI  - STAT5 proteins are involved in down-regulation of iron regulatory protein 1 gene
      expression by nitric oxide.
AB  - RNA-binding activity of IRP1 (iron regulatory protein 1) is regulated by the
      insertion/extrusion of a [4Fe-4S] cluster into/from the IRP1 molecule. NO (nitic
      oxide), whose ability to activate IRP1 by removing its [4Fe-4S] cluster is well
      known, has also been shown to down-regulate expression of the IRP1 gene. In the
      present study, we examine whether this regulation occurs at the transcriptional
      level. Analysis of the mouse IRP1 promoter sequence revealed two conserved
      putative binding sites for transcription factor(s) regulated by NO and/or changes
      in intracellular iron level: Sp1 (promoter-selective transcription factor 1) and
      MTF1 (metal transcription factor 1), plus GAS (interferon-gamma-activated
      sequence), a binding site for STAT (signal transducer and activator of
      transcription) proteins. In order to define the functional activity of these
      sequences, reporter constructs were generated through the insertion of
      overlapping fragments of the mouse IRP1 promoter upstream of the luciferase gene.
      Transient expression assays following transfection of HuH7 cells with these
      plasmids revealed that while both the Sp1 and GAS sequences are involved in basal
      transcriptional activity of the IRP1 promoter, the role of the latter is
      predominant. Analysis of protein binding to these sequences in EMSAs
      (electrophoretic mobility-shift assays) using nuclear extracts from mouse RAW
      264.7 macrophages stimulated to synthesize NO showed a significant decrease in
      the formation of Sp1-DNA and STAT-DNA complexes, compared with controls. We have
      also demonstrated that the GAS sequence is involved in NO-dependent down
      regulation of IRP1 transcription. Further analysis revealed that levels of STAT5a
      and STAT5b in the nucleus and cytosol of NO-producing macrophages are
      substantially lower than in control cells. These findings provide evidence that
      STAT5 proteins play a role in NO-mediated down-regulation of IRP1 gene
      expression.

PMID- 16886907
TI  - NF-Y, AP2, Nrf1 and Sp1 regulate the fragile X-related gene 2 (FXR2).
AB  - Fragile X syndrome, the most common heritable form of mental retardation, is
      caused by silencing of the FMR1 (fragile X mental retardation-1 gene). The
      protein product of this gene, FMRP (fragile X mental retardation protein), is
      thought to be involved in the translational regulation of mRNAs important for
      learning and memory. In mammals, there are two homologues of FMRP, namely FXR1P
      (fragile X-related protein 1) and FXR2P. Disruption of Fxr2 in mice produces
      learning and memory deficits, and Fmr1 and Fxr2 double-knockout mice have
      exaggerated impairments in certain neurobehavioral phenotypes relative to the
      single gene knockouts. This has led to the suggestion that FMR1 and FXR2
      functionally overlap and that increasing the expression of FXR2P may ameliorate
      the symptoms of an FMRP deficiency. Interestingly, the region upstream of the
      FXR2 translation start site acts as a bidirectional promoter in rodents, driving
      transcription of an alternative transcript encoding the ABP (androgen-binding
      protein) [aABP (alternative ABP promoter)]. To understand the regulation of the
      human FXR2 gene, we cloned the evolutionarily conserved region upstream of the
      FXR2 translation start site and showed that it also has bidirectional promoter
      activity in both neuronal and muscle cells as evidenced by luciferase reporter
      assay studies. Alignment of the human, mouse, rat, rabbit and dog promoters
      reveals several highly conserved transcription factor-binding sites. Gel
      electrophoretic mobility-shift assays, chromatin immunoprecipitation studies and
      co-transfection experiments with plasmids expressing these transcription factors
      or dominant-negative versions of these factors showed that NF-YA (nuclear
      transcription factor Yalpha), AP2 (activator protein 2), Nrf1 (nuclear
      respiratory factor/alpha-Pal) and Sp1 (specificity protein 1) all bind to the
      FXR2 promoter both in vitro and in vivo and positively regulate the FXR2
      promoter.

PMID- 16886908
TI  - Selection and characterization of an internalizing epidermal-growth-factor
      receptor antibody.
AB  - Antibody-therapeutic agent conjugates to be delivered directly into the cytosol
      of tumour cells is required for many target-based therapeutic strategies. For
      this work, a large non-immune phage-display library was used to select
      internalizing scFv (single chain variable fragment) directed against EGFR
      (epidermal growth factor receptor), a tyrosine kinase receptor that is
      overexpressed in a wide range of tumour cells. The CHO-EGFR-GFP1 (where CHO is
      Chinese-hamster ovary) cell line, a transfected cell line expressing EGFR-GFP
      (green fluorescent protein) fusion protein on membranes, and the untransfected
      cell line CHO-K1 were used as EGFR-positive cells and -negative cells
      respectively in the subtractive selection procedure. A novel human anti-EGFR scFv
      (F4-scFv) was isolated. F4-scFv bound native EGFR-bearing cell lines and could be
      internalized, but did not bind EGFR-negative cell lines. The K(D) value of F4
      scFv was 472 nM as determined on A431 cells. F4-scFv could be used to target
      therapeutic agents into tumour cells and was expected to be non-immunogenic in
      humans. Use of a transfected cell line expressing GFP-tagged receptors allows
      selection and characterization of antibodies to native receptors without the need
      for protein expression and purification, significantly speeding up the generation
      of targeting antibodies.

PMID- 16886910
TI  - Review article: management of hepatic disease following haematopoietic cell
      transplant.
AB  - Hepatic diseases are common complications of haematopoietic cell transplant. The
      causes are multiple: myeloablative conditioning regimens may cause sinusoidal
      injury; acute and chronic graft-versus-host disease lead to damaged hepatocytes
      and small bile ducts; microcrystalline deposits in the gall bladder can cause
      biliary symptoms; drug-induced liver injury is common; and the liver may be
      infected by viruses and fungi during the period of severe immune suppression that
      follows transplant. Pre-transplant evaluation and prevention of liver injury are
      often more useful than treatment of deeply jaundiced patients in improving
      transplant outcomes. This review covers pre-transplant evaluation, common
      hepatobiliary problems in the six months following transplant, and hepatic
      problems in long-term survivors.

PMID- 16886909
TI  - Spatial segregation of transport and signalling functions between human
      endothelial caveolae and lipid raft proteomes.
AB  - Lipid rafts and caveolae are biochemically similar, specialized domains of the PM
      (plasma membrane) that cluster specific proteins. However, they are
      morphologically distinct, implying different, possibly complementary functions.
      Two-dimensional gel electrophoresis preceding identification of proteins by MS
      was used to compare the relative abundance of proteins in DRMs (detergent
      resistant membranes) isolated from HUVEC (human umbilical-vein endothelial
      cells), and caveolae immunopurified from DRM fractions. Various signalling and
      transport proteins were identified and additional cell-surface biotinylation
      revealed the majority to be exposed, demonstrating their presence at the PM. In
      resting endothelial cells, the scaffold of immunoisolated caveolae consists of
      only few resident proteins, related to structure [CAV1 (caveolin-1), vimentin]
      and transport (V-ATPase), as well as the GPI (glycosylphosphatidylinositol)
      linked, surface-exposed protein CD59. Further quantitative characterization by
      immunoblotting and confocal microscopy of well-known [eNOS (endothelial nitric
      oxide synthase) and CAV1], less known [SNAP-23 (23 kDa synaptosome-associated
      protein) and BASP1 (brain acid soluble protein 1)] and novel [C8ORF2 (chromosome
      8 open reading frame 2)] proteins showed different subcellular distributions with
      none of these proteins being exclusive to either caveolae or DRM. However, the
      DRM-associated fraction of the novel protein C8ORF2 (approximately 5% of total
      protein) associated with immunoseparated caveolae, in contrast with the raft
      protein SNAP-23. The segregation of caveolae from lipid rafts was visually
      confirmed in proliferating cells, where CAV1 was spatially separated from eNOS,
      SNAP-23 and BASP1. These results provide direct evidence for the previously
      suggested segregation of transport and signalling functions between specialized
      domains of the endothelial plasma membrane.

PMID- 16886911
TI  - Review article: scoring systems for assessing prognosis in critically ill adult
      cirrhotics.
AB  - BACKGROUND: Cirrhotic patients admitted to intensive care units (ICU) still have
      poor outcomes. Some current ICU prognostic models [Acute Physiology and Chronic
      Health Evaluation (APACHE), Organ System Failure (OSF) and Sequential Organ
      Failure Assessment (SOFA)] were used to stratify cirrhotics into risk categories,
      but few cirrhotics were included in the original model development. Liver
      specific scores [Child-Turcotte-Pugh (CTP) and model for end-stage liver disease
      (MELD)] could be useful in this setting. AIM: To evaluate whether ICU prognostic
      models perform better compared with liver-disease specific ones in cirrhotics
      admitted to ICU. METHODS: We performed a structured literature review identifying
      clinical studies focusing on prognosis and risk factors for mortality in adult
      cirrhotics admitted to ICU. RESULTS: We found 21 studies (five solely dealing
      with gastrointestinal bleeding) published during the last 20 years (54-420
      patients in each). APACHE II and III, SOFA and OSF had better discrimination for
      correctly predicting death compared with the CTP score. The MELD score was
      evaluated only in one study and had good predictive accuracy [receiver operator
      characteristic (ROC) curve: 0.81). Organ dysfunction models (OSF, SOFA) were
      superior compared with APACHE II and III (ROC curve: range 0.83-0.94 vs. 0.66
      0.88 respectively). Cardiovascular, liver and renal system dysfunction were more
      frequently independently associated with mortality. CONCLUSIONS: General-ICU
      models had better performance in cirrhotic populations compared with CTP score;
      OSF and SOFA had the best predictive ability. Further prospective and validation
      studies are needed.

PMID- 16886912
TI  - Review article: evolutionary advances in the delivery of aminosalicylates for the
      treatment of ulcerative colitis.
AB  - Ulcerative colitis is a chronic and debilitating disease that involves
      inflammation of the colonic mucosa. Current therapies aim to reduce the symptom
      burden of ulcerative colitis and maintain disease quiescence. The standard first
      line treatment for mild-to-moderate ulcerative colitis is 5-aminosalicylate
      therapy, which is available in oral and rectal (topical) formulations. While
      current 5-aminosalicylate formulations are effective in the majority of patients,
      they are associated with a number of limitations including inconvenient dosing
      regimens and poor patient acceptability, which may lead to non-compliance with
      prescribed therapy. A variety of improved delivery mechanisms have been developed
      in an effort to overcome these limitations. Micropellet formulations and high
      dose tablets appear to offer comparable efficacy and tolerability to conventional
      formulations, although any benefit in terms of long-term patient compliance
      remains to be proven. Novel methods of delivery, such as those using a
      combination of hydrophilic and lipophilic matrices, designed to provide once
      daily dosing in a high-strength tablet, may offer a significant improvement in
      the therapy of active and quiescent ulcerative colitis. This review examines the
      limitations of current 5-aminosalicylate formulations and reports on the
      evolution of novel oral formulations designed to overcome these limitations,
      maximize patient compliance during both induction and maintenance of quiescence,
      and optimize overall clinical outcomes.

PMID- 16886913
TI  - Review article: current and emerging therapies for functional dyspepsia.
AB  - Functional dyspepsia represents a heterogeneous group of gastrointestinal
      disorders marked by the presence of upper abdominal pain or discomfort. Although
      its precise definition has evolved over the last several decades, this disorder
      remains shrouded in controversy. The symptoms of functional dyspepsia may overlap
      with those of other functional bowel disorders including irritable bowel syndrome
      and non-erosive reflux disease. There may be coexistent psychological distress or
      disease complicating its presentation and response to therapy. Given the
      prevalence and chronicity of functional dyspepsia, it remains a great burden to
      society. Suspected physiological mechanisms underlying functional dyspepsia
      include altered motility, altered visceral sensation, inflammation, nervous
      system dysregulation and psychological distress. Yet the exact pathophysiological
      mechanisms that cause symptoms in an individual patient remain difficult to
      delineate. Numerous treatment modalities have been employed including dietary
      modifications, pharmacological agents directed at various targets within the
      gastrointestinal tract and central nervous system, psychological therapies and
      more recently, complementary and alternative treatments. Unfortunately, to date,
      all of these therapies have yielded only marginal results. A variety of emerging
      therapies are being developed for functional dyspepsia. Most of these therapies
      are intended to normalize pain perception and gastrointestinal motor and reflex
      function in this group of patients.

PMID- 16886914
TI  - Personal view: crystalloid transfusion in acute gastrointestinal haemorrhage: is
      it beneficial? An historical perspective.
AB  - The conventional management of acute gastrointestinal haemorrhage mandates early
      repletion of blood volume with crystalloids and blood, as part of the initial
      management, where there is evidence of hypovolaemia. Meanwhile there is a major
      trend towards a restrained use of fluid to raise blood pressure to near normal
      for the bleeding patient in trauma and similar emergencies. This divergence of
      view requires analysis. An Ovid/MEDLINE, Google and extensive literature search
      focused on the resuscitation and transfusion of bleeding trauma patients was
      performed. In addition to clear evidence from animal experiments that early
      restoration of blood volume perpetuates bleeding, there is considerable evidence
      in humans - both in war and civilian life - that rapid crystalloid infusion is
      harmful. I also report a personal series of benefit from restricted transfusion
      in acute upper gastrointestinal haemorrhage in humans. Given the lack of evidence
      of benefit for rapid blood volume repletion in acute gastrointestinal
      haemorrhage, there is need for controlled studies of the most appropriate
      approach to crystalloid transfusion in acute gastrointestinal bleeding.

PMID- 16886915
TI  - Meta-analysis: intradermal vs. intramuscular vaccination against hepatitis B
      virus in patients with chronic kidney disease.
AB  - BACKGROUND: Dialysis patients have suboptimal response towards hepatitis B virus
      (HBV) vaccine and intradermal hepatitis B virus vaccination has been used to
      improve the response rate; however, its efficacy remains unclear. DESIGN: Meta
      analysis of controlled trials comparing intradermal vs. intramuscular vaccine
      against HBV among chronic kidney disease patients. IDENTIFICATION: Twelve studies
      involving 640 unique patients were included if they had controlled design,
      intervention and control group patients received intradermal or intramuscular
      vaccine against HBV, respectively. Patients were followed for a minimum of 7
      months after the first vaccine dose. MAIN OUTCOME MEASURES: The odds ratio of
      failure to respond to HBV vaccine among patients who received vaccine by
      intradermal vs. intramuscular route was the end point of interest. It was
      calculated at completion of HBV vaccination and over follow-up. RESULTS: Pooling
      of study results demonstrated a decreased risk of failure to respond to HBV
      vaccine among patients who were vaccinated by intradermal vs. intramuscular route
      (pooled odds ratio at completion of vaccine protocol: 0.36; 95% CI: 0.21-0.62;
      test of study heterogeneity, P = 0.089). This difference did not occur over
      follow-up (6-60 months after completing vaccine schedule; pooled odds ratio: 1.1;
      95% CI: 0.47-2.5). CONCLUSIONS: Dialysis patients show higher seroprotection
      after intradermal than intramuscular vaccination schedules; this was not apparent
      over follow-up. Further studies are warranted to assess if the higher
      seroprotection rates obtained by intradermal route translates into reduced
      incidence of de novo HBV virus among chronic kidney disease patients.

PMID- 16886916
TI  - Long-term reversal of hypocholesterolaemia in patients with chronic hepatitis C
      is related to sustained viral response and viral genotype.
AB  - BACKGROUND: Genotype-3 of hepatitis C virus (HCV) has been associated with serum
      lipid changes (reversible with sustained viral response) and liver steatosis.
      AIM: To characterize the relationships among hepatic steatosis, cholesterol and
      sustained viral response in these patients. METHODS: Patients (n = 215) with
      chronic hepatitis C (157 with genotype-1 of HCV) had age, body mass index,
      gender, alcohol intake, glycaemia, serum lipids, transaminases, grade and stage
      (METAVIR and Scheuer), degree of liver steatosis, sustained viral response,
      insulinaemia, leptinaemia, beta-hydroxybutyrate and glycerol measured, and were
      compared with 32 hepatitis B virus (HBV)-infected subjects. RESULTS: Genotype-3
      of HCV patients had age-adjusted hypocholesterolaemia and more frequent hepatic
      steatosis (P < 0.001). Steatosis was inversely correlated with serum cholesterol
      (P < 0.01) and directly with viral load (P < 0.03). In patients with genotype-3
      of HCV and sustained viral response, serum cholesterol increased from 138 (95%
      CI: 120-151) to 180 mg/dL (95% CI: 171-199) 12 months after treatment conclusion
      (P < 0.0001). By contrast, cholesterol values were unchanged in genotype-3 of HCV
      non-responders and in patients with genotype-1 of HCV regardless of response.
      Rising cholesterol in sustained viral response did not parallel the changes in
      beta-hydroxybutyrate. CONCLUSIONS: Besides causing hepatic steatosis, genotype-3
      specifically decreases serum cholesterol. This interference with the metabolic
      lipid pathway is related to viral load, is reversed with sustained viral
      response, and seems unrelated to mitochondrial dysfunction.

PMID- 16886917
TI  - Transient elastography: a valid alternative to biopsy in patients with chronic
      liver disease.
AB  - BACKGROUND: Transient elastography is a novel and non-invasive technique for the
      evaluation of fibrosis in chronic liver disease. Few studies that exist value the
      efficacy of transient elastography, mainly in hepatitis C virus-infected
      patients. AIM: To evaluate the effectiveness, objectivity, reproducibility and
      safety of this technique. METHODS: We included 103 consecutive patients who
      underwent a liver biopsy in the last 48 months with a wide spectrum of chronic
      liver diseases. Median stiffness value (expressed as kilopascals - kPa) was kept
      as representative of the liver elastic modulus. All biopsy specimens were
      analysed by the same pathologist according to the METAVIR scoring system.
      RESULTS: Median value of stiffness in patients with mild or moderate fibrosis (FI
      and FII), and severe fibrosis or cirrhosis (FIII and FIV) was of 7, 4 +/- 5 and
      16, 4 +/- 10 kPa, respectively, with a significant difference between them (P <
      0.05). The areas under the receiver operating characteristic curves showed the
      optimal liver stiffness cut-off values for each group. CONCLUSIONS: We found a
      positive correlation between the liver stiffness found by transient elastography
      and fibrosis stage on biopsy in all patients, independently of the liver disease
      aetiology. Transient elastography is an easy, quick to perform and safe non
      invasive procedure, reliable for assessing liver fibrosis.

PMID- 16886918
TI  - Clinical features of Japanese male patients with type 1 autoimmune hepatitis.
AB  - BACKGROUND: Recently, unusual patients with autoimmune hepatitis, such as male
      patients, have increased. AIM: To assess clinical feature of Japanese males with
      type 1 autoimmune hepatitis compared with females. METHODS: We investigated
      consecutive 160 patients with type 1 autoimmune hepatitis, who consisted of 20
      males and 140 females, with a median age of 55 (16-79) years. RESULTS: Compared
      with females, males had a lower frequency of definite diagnosis according to the
      revised scoring system proposed by the International Autoimmune Hepatitis Group
      (40% vs. 85%) and lower serum levels of immunoglobulin G [1932 (1085-3850) mg/dL
      vs. 2624 (1354-6562) mg/dL]. However, they were similar in age, form of clinical
      onset, symptomatic concurrent autoimmune disease, human leucocyte antigen DR
      status and frequency of cirrhosis at the time of diagnosis. The normalization of
      serum alanine aminotransferase levels within 6 months after the introduction of
      corticosteroid treatment was lower in males compared with females (73% vs. 93%).
      CONCLUSIONS: In male patients, a diagnosis of autoimmune hepatitis should be made
      carefully. In Japanese patients with a dominant frequency of human leucocyte
      antigen DR4, gender may affect the response to corticosteroid treatment.

PMID- 16886919
TI  - Interferon-alpha therapy in HBeAg-negative chronic hepatitis B: a long-term
      prospective study from north-western Greece.
AB  - AIMS: To determine the long-term response to interferon-alpha therapy in patients
      with hepatitis B e antigen-negative chronic hepatitis B, and the factors
      independently associated with response and survival. METHODS: Sixty-three
      patients with documented hepatitis B e antigen-negative chronic hepatitis B
      treated with interferon-alpha for a year were followed-up for a period of 6
      years. RESULTS: Sustained biochemical and virological response was seen in 34.91%
      and 33.33% of patients at 6 and 12 months of follow-up, respectively, and
      histological improvement in 54.5% of sustained responders compared with non
      responders (7.1%, P = 0.004, chi-squared test), at 6 months of follow-up.
      Multivariate analysis showed that patients with hepatitis B virus-DNA levels at 6
      months of treatment <10,000 copies/mL had a low probability of relapse, compared
      with those with levels >10 000 copies/mL (P = 0.032). Age (>65 years) and
      hepatitis B virus-DNA level at 6 months of treatment (>10,000 copies/mL) were the
      independent factors for disease progression and survival (P = 0.041 and P = 0.044
      respectively). At 6 years, a sustained response was still present in 19.04% of
      patients and 4.8% of them had developed anti-HBs. CONCLUSION: Hepatitis B virus
      DNA monitoring by quantitative polymerase chain reaction at 6 months of treatment
      may allow for early prediction of response to interferon-alpha, and may serve as
      an indicator of disease progression in the future.

PMID- 16886920
TI  - Coexistence between colorectal cancer/adenoma and coronary artery disease:
      results from 1382 patients.
AB  - BACKGROUND: Common risk factors exist in colorectal neoplasia (cancer or adenoma)
      and coronary artery disease. AIM: To investigate in a retrospective study if
      there is coexistence of the two events in patients > OR =50 years. METHODS:
      Computer data on colonoscopies performed on symptomatic patients, the
      corresponding medical record and colonic histology in 1997-2000 were retrieved.
      History of coronary artery disease was recorded. To adjust for the factors of age
      and sex, bivariate logistic regression analysis was used to test for coexistence.
      RESULTS: 1382 patients were recruited. Colorectal neoplasia and history of
      coronary artery disease were present in 27% (373) and 12% (167) of patients,
      respectively. The mean age of patients was older in colorectal neoplasia+ (75 +/-
      11 vs. 69 +/- 13 years, P < 0.0001) and in coronary artery disease+ (79 +/- 9 vs.
      69 +/- 12 years, P < 0.0001) patients. Male was the predominant sex in colorectal
      neoplasia+: 33% vs. 22% (P < 0.0001), but not in coronary artery disease+ (P =
      0.29). Colorectal neoplasia+ patients were more likely to have coronary artery
      disease+ [21.2% (79/373) vs. 8.8% (89/1098) (P < 0.0001)]. Bivariate logistic
      regression analysis showed strong association between the two events (OR: 2.12,
      95% CI: 1.5, 3.0). CONCLUSION: There is strong coexistence of colorectal
      neoplasia and coronary artery disease, probably due to exposure to common risk
      factors.

PMID- 16886921
TI  - Immunoglobulin A autoantibodies against transglutaminase 2 in the small
      intestinal mucosa predict forthcoming coeliac disease.
AB  - BACKGROUND: Reliable markers of early developing coeliac diseases are needed.
      Coeliac autoantibodies in the serum or Marsh I inflammation may be indicators of
      subsequent coeliac disease. AIM: To investigate whether determination of
      intestinal transglutaminase 2-targeted autoantibody deposits would detect early
      developing coeliac disease better than previous methods. METHODS: The study
      investigated patients previously excluded for coeliac disease: 25 had positive
      serum coeliac autoantibodies (endomysial), 25 antibody-negative had Marsh I, and
      25 antibody-negative had Marsh 0 finding. Seven (median) years after baseline
      investigation, new coeliac cases were recorded, and small bowel biopsy was
      offered to the rest of the patients. Serum and intestinal coeliac autoantibodies
      and intraepithelial lymphocytes were assessed as indicators of developing coeliac
      disease. RESULTS: Seventeen patients had developed coeliac disease: 13 in the
      autoantibody-positive group, three in the Marsh I group and one in the Marsh 0
      group. At baseline, intestinal coeliac autoantibody deposits had a sensitivity
      and specificity of 93% and 93% in detecting subsequent coeliac disease, CD3+ 59%
      and 57%, gammadelta+ 76% and 60%, and villous tip intraepithelial lymphocytes 88%
      and 71%, respectively. CONCLUSIONS: Endomysial antibodies with normal histology
      indicates early developing coeliac disease. Transglutaminase 2-targeted
      intestinal autoantibody deposits proved the best predictor of subsequent coeliac
      disease.

PMID- 16886922
TI  - Serum levels of soluble CD163 correlate with the inflammatory process in coeliac
      disease.
AB  - BACKGROUND: In coeliac disease, following the introduction of a gluten-free diet,
      monitoring mucosal disease activity requires repeated small intestinal biopsies.
      If a test measuring a circulating inflammatory marker was available, this would
      be clinically valuable. AIM: To determine if levels of soluble CD163, a scavenger
      receptor shed by tissue macrophages, correlated with the inflammatory lesion in
      coeliac disease. METHODS: Serum samples were collected from 131 patients with
      untreated coeliac disease, 40 patients with treated coeliac disease, 92 non
      coeliac disease control subjects and 131 healthy controls. A capture enzyme
      linked immunosorbance assay was established to measure levels of soluble CD163 in
      sera. The extent of the histological lesion in coeliac biopsies was assessed
      using a Marsh grading system. RESULTS: Levels of CD163 in untreated coeliac
      subjects were significantly elevated when compared with the treated coeliac
      patients, the disease control group and the healthy control subjects (P < 0.0001
      in each instance). Moreover, coeliac patients with the most marked histological
      lesion (Marsh 3) had significantly higher levels of soluble CD163 than patients
      with Marsh grade 2 lesions (P < 0.0004), with grade 1 lesions (P < 0.0001) and
      grade 0 lesions (P < 0.0001). CONCLUSIONS: Measurement of soluble CD163 may be a
      useful method of monitoring the inflammatory lesion in coeliac disease.

PMID- 16886923
TI  - A higher diagnostic profile is possible for microscopic colitis.

PMID- 16886925
TI  - Diaries and calendars for migraine. A review.
AB  - Headache is one of the most common types of pain and, in the absence of
      biological markers, headache diagnosis depends only on information obtained from
      clinical interviews and physical and neurological examinations. Headache diaries
      make it possible to record prospectively the characteristics of every attack and
      the use of headache calendars is indicated for evaluating the time pattern of
      headache, identifying aggravating factors and evaluating the efficacy of
      preventive treatment. This may reduce the recall bias and increase accuracy in
      the description. The use of diagnostic headache diaries does have some
      limitations because the patient's general acceptance is still limited and some
      subjects are not able to fill in a diary. In this review, we considered diaries
      and calendars especially designed for migraine and, in particular, we aimed at:
      (i) determining what instruments are available in clinical practice for diagnosis
      and follow-up of treatments; and (ii) describing the tools that have been
      developed for research and their main applications in the headache field. In
      addition to the literature review, we added two paragraphs concerning the
      authors' experience of the use of diaries and calendars in headache centres and
      their proposals for future areas of research.

PMID- 16886926
TI  - Side-shifting hemicrania continua with aura (migraine with aura with autonomic
      symptoms responsive to indomethacin?).
AB  - Atypical features of hemicrania continua (HC), including both visual aura and
      side shifting, have been reported previously. However, auras and variable
      unilaterality have never been reported together in HC. We report two patients
      with side-shifting HC with aura. These patients' symptoms are unilateral
      headaches, visual aura, autonomic features, throbbing pain, nausea and
      photo/phonophobia. One could speculate that the unilaterality and/or the
      autonomic symptom modules are indomethacin responsive. The patients can also be
      classified as chronic migraine with aura, with autonomic symptoms, responsive to
      indomethacin. Neither migraine subtype nor side-shifting HC with aura is included
      in the current International Headache Society (IHS) classification, so these
      patients are not classifiable. Side-shifting HC with aura implies the need to
      revisit the traditional IHS categorization of headaches into unique diagnostic
      groups. The modular headache theory may be a tool for the understanding of these
      rare and complex cases.

PMID- 16886927
TI  - The impact of different antimigraine compounds on platelet and erythrocyte
      aggregation.
AB  - Clinical and experimental data suggest that ergotamine compounds and triptans may
      contribute to vascular events such as myocardial infarction and stroke. The role
      of blood cell aggregation in this context is, however, not clarified. We aimed to
      evaluate the impact of different acute antimigraine compounds on platelet and
      erythrocyte aggregation in a human ex vivo experimental design. In 20 healthy
      subjects without migraine and in 20 healthy subjects with migraine without aura,
      platelet and erythrocyte aggregation were measured before and after intake of
      placebo, acetylsalicylic acid, ergotamine tartrate, zolmitriptan and sumatriptan.
      Platelet aggregation was measured by the so-called platelet reactivity index.
      Erythrocyte aggregation was measured by photometric assessment in an
      aggregometer. Ergotamine tartrate induced a significant increase of platelet
      aggregation, whereas acetylsalicylic acid induced a significant decrease in both
      subject groups. After placebo, after sumatriptan and after zolmitriptan, no
      significant changes of platelet aggregation were noted. Erythrocyte aggregation
      was affected by neither compound. We can conclude that platelet aggregation, but
      not erythrocyte aggregation, is increased after intake of ergotamine tartrate.
      This may in part contribute to vascular side-effects of this compound.
      Acetylsalicylic acid and the triptans appeared to be safe with respect to
      platelet and erythrocyte aggregation.

PMID- 16886928
TI  - Dipyridamole may induce migraine in patients with migraine without aura.
AB  - Dipyridamole inhibits phosphodiesterase 5 (PDE5) and adenosine re-uptake. The
      most prominent side-effect is headache. We examined the migraine-generating
      effects of dipyridamole as well as the cerebral blood velocity response in a
      single-blind study, including 10 patients with migraine without aura and 10
      healthy subjects. Dipyridamole 0.142 mg/kg per min was administered
      intravenously. Headache intensity was scored on a verbal rating scale along with
      pain characteristics and accompanying symptoms. Blood velocity in the middle
      cerebral artery (V(mca)), blood pressure and heart rate were recorded repeatedly.
      Headache was induced in all migraine patients and in eight of 10 healthy subjects
      (P = 0.47) with no significant difference in headache intensity (P = 0.53).
      However, five patients but only one healthy subject experienced the symptoms of
      migraine without aura, according to ICHD-2 criteria, within 12 h (P = 0.14). Four
      patients reported photophobia after dipyridamole compared with no healthy
      subjects (P = 0.087). V(mca) decreased (P < 0.001) during and after dipyridamole
      infusion with no difference between groups (P = 0.15) coinciding with initiation,
      but not cessation of immediate headache. Thus, dipyridamole induces symptoms of
      migraine and an initial decrease in V(mca) in migraine patients, but not
      significantly more than in healthy subjects. This relatively low frequency of
      migraine induction, compared with nitric oxide donors and sildenafil, is probably
      due to the less specific action of dipyridamole on the cGMP signalling pathway as
      well as a possible bidirectional effect of adenosine on migraine induction.

PMID- 16886929
TI  - Prevalence of patent foramen ovale in migraine patients with and without aura
      compared with stroke patients. A transcranial Doppler study.
AB  - The aim of this study was to investigate the prevalence of patent foramen ovale
      (PFO) in a consecutive unselected cohort of migraine patients (with and without
      aura) and compare it with a group of ischaemic young and elderly stroke patients.
      One hundred and forty-one migraine patients were compared with 330 stroke
      patients (130 young patients; 200 elderly patients) selected from our hospital
      stroke data bank. PFO was assessed with transcranial Doppler sonography with i.v.
      injection of agitated saline. The prevalence of PFO was 51.7% in migraine with
      aura (MA) patients, 33.7% in migraine without aura (MoA) patients, 33.8% in young
      stroke patients and 20.5% in elderly stroke patients (P < 0.001). The prevalence
      of PFO in cryptogenic stroke in young and elderly stroke patients was,
      respectively, 41.1% and 25% (P = 0.04). The difference between MA and MoA
      patients was significant (odds ratio = 2.1). The prevalence of PFO in MA patients
      is higher than in MoA patients and in young cryptogenic stroke patients.

PMID- 16886930
TI  - Generalized hyperalgesia in patients with chronic tension-type headache.
AB  - Increased pain sensitivity in the central nervous system may play an important
      role in the pathophysiology of chronic tension-type headache (CTTH). Previous
      studies using pain thresholds as a measure of central pain sensitivity have
      yielded inconsistent results and only a few studies have examined perception of
      muscle pain without involvement of adjacent tissues. It has been suggested that
      suprathreshold testing might be more sensitive than threshold measurements in
      evaluation of central hyperexcitability in CTTH. The aim of the study was to
      compare pain ratings to suprathreshold single and repetitive (2 Hz) electrical
      stimulation of muscle and skin in cephalic (temporal and trapezius) and
      extracephalic (anterior tibial) regions between patients with CTTH and healthy
      subjects. In addition, we aimed to examine gender differences in pain ratings to
      suprathreshold stimulation and degree of temporal summation of pain between
      patients and controls. Pain ratings to both single and repetitive suprathreshold
      stimulation were higher in patients than in controls in both skin and muscle in
      all examined cephalic and extracephalic regions (P < 0.04). Pain ratings to both
      single and repetitive suprathreshold electrical stimulation were significantly
      higher in female compared with male patients (P < 0.001) and in female compared
      with male controls (P < or = 0.001). The degree of temporal summation of muscular
      and cutaneous pain tended to be higher in patients than in controls but the
      differences were not statistically different. This study provides evidence for
      generalized increased pain sensitivity in CTTH and strongly suggests that pain
      processing in the central nervous system is abnormal in this disorder.
      Furthermore, it indicates that suprathreshold stimulation is more sensitive than
      recording of pain thresholds for evaluation of generalized pain perception.

PMID- 16886931
TI  - Do migraineurs have difficulty judging direction of simulated heading?
AB  - Some migraineurs have increased thresholds for the detection of global dot
      motion. We investigated whether migraineurs show consequential abnormalities in
      the determination of direction of self-motion (heading) from simulated optic
      flow. The ability to determine heading from optic flow is likely to be necessary
      for optimal determination of self-motion through the environment. Twenty-five
      migraineurs and 25 controls participated. Global dot motion coherence thresholds
      were assessed, in addition to performance on two simulated heading tasks: one
      with a symmetrical flow field, and the second with differing velocity of optic
      flow on the left and right sides of the participant. While some migraineurs
      demonstrated abnormal global motion coherence thresholds, there was no difference
      in performance on the heading tasks at either simulated walking (5 km/h) or
      driving (50 km/h) speeds. Increased global motion coherence thresholds in
      migraineurs do not result in abnormal judgements of heading from 100% coherent
      optic flow.

PMID- 16886932
TI  - Sick leave is related to frequencies of migraine and non-migrainous headache--The
      HUNT Study.
AB  - The aim of this large, cross-sectional, population-based study was to examine the
      association between sick leave and headache. Between 1995 and 1997, all 92 566
      adults in Nord-Trondelag County in Norway were invited to participate in a health
      survey. Out of 73 327 invited individuals <67 years old, a total of 38 192 (52%)
      responded to questions about headache, work situation and sick leave during the
      past year. Associations between sick leave, headache and migraine included were
      assessed in multivariate analyses, estimating prevalence odds ratios (ORs) with
      95% confidence intervals (CIs). There was an increasing prevalence of sick leave
      with increasing frequency of migraine and non-migrainous headache. The prevalence
      of sick leave >8 weeks during the past year was more than three times higher
      among individuals with headache >14 days per month (20%) compared with those
      without headache (6%). The results may indicate that better treatment of
      individuals with chronic headache may have beneficial economic implications.

PMID- 16886933
TI  - Abnormal platelet trace amine profiles in migraine with and without aura.
AB  - Trace amines, including tyramine, octopamine and synephrine, are closely related
      to classic biogenic amines. In one study, where these substances were found
      elevated in plasma of migraineurs, it was hypothesized that trace amine
      metabolism is deranged in migraine. To confirm these findings, we studied, using
      a multichannel electrochemical high-performance liquid chromatography system, the
      concentrations of trace amines in platelets of migraine without aura (MoA) and
      migraine with aura (MA) patients in headache-free period, compared with controls.
      Platelet concentrations of trace amines, although elevated in both migraine
      types, showed a different profile in MoA and MA. Octopamine was significantly
      higher in MoA sufferers (0.69 +/- 0.43 ng/10(8) platelets) compared with both
      control subjects (0.22 +/- 0.16 ng/10(8) platelets) and MA patients (0.39 +/-
      0.37 ng/10(8) platelets). Synephrine was significantly higher in MA patients
      (0.72 +/- 0.44 ng/10(8) platelets) with respect to both controls (0.33 +/- 0.25
      ng/10(8) platelets) and MoA sufferers (0.37 +/- 0.29 ng/10(8) platelets). These
      results strengthen the hypothesis that tyrosine metabolism is deranged in
      migraine and may participate in its pathophysiology.

PMID- 16886935
TI  - Efficacy of physiotherapy including a craniocervical training programme for
      tension-type headache; a randomized clinical trial.
AB  - We conducted a multicentre, randomized controlled trial with blinded outcome
      assessment. The treatment period was 6 weeks with follow-up assessment
      immediately thereafter and after 6 months. The objective was to determine the
      effectiveness of a craniocervical training programme combined with physiotherapy
      for tension-type headache. Eighty-one participants meeting the diagnostic
      criteria for tension-type headache were randomly assigned to an exercise group
      (physiotherapy and an additional craniocervical training programme) and a control
      group (physiotherapy alone). The primary outcome measure was headache frequency.
      Secondary outcomes included headache intensity and duration, Quality of Life (SF
      36) and the Multidimensional Headache Locus of Control scale (MHLC). At 6 months'
      follow-up, the craniocervical training group showed significantly reduced
      headache frequency, intensity and duration (P < 0.001 for all). Effect sizes were
      large and clinically relevant. Loss to follow-up amounted to 3.7%. Physiotherapy
      including craniocervical training reduces symptoms of tension-type headache
      significantly over a prolonged time frame.

PMID- 16886936
TI  - Vasoactive intestinal polypeptide evokes only a minimal headache in healthy
      volunteers.
AB  - The role of the parasympathetic nervous system in the pathogenesis of migraine is
      disputed. The headache-eliciting effect of the parasympathetic neurotransmitter,
      vasoactive intestinal polypeptide (VIP), and its effect on cerebral arteries and
      brain haemodynamics has not been systematically studied in man. We hypothesized
      that infusion of VIP might induce headache in healthy subjects and cause changes
      in cerebral haemodynamics. VIP (8 pmol/kg per min) or placebo (0.9% saline) was
      infused for 25 min into 12 healthy young volunteers in a crossover, double-blind
      design. Headache was scored on a verbal rating scale from 0 to 10, regional
      cerebral blood flow (rCBF) was measured with single-photon emission computed
      tomography and (133)Xe inhalation and mean flow velocity in the middle cerebral
      artery (V(meanMCA)) was measured with transcranial Doppler ultrasonography. The
      headache was very mild with a maximum score of 2 and described as a pressing or
      throbbing sensation. Five participants developed headache during VIP and one
      during placebo. During the infusion, a significant drop in V(meanMCA) was seen
      for VIP compared with placebo (P < 0.001), but the effect quickly waned and no
      difference was found when comparing the time between 30 and 120 min. In addition,
      no significant difference in the diameter of the MCA could be found during the
      infusion. No significant differences in rCBF (P = 0.10) were found between VIP
      and placebo. A marked dilation of the superficial temporal artery was seen (P =
      0.04) after VIP in the first 30 min but no difference was found when comparing
      the time between 30 and 120 min. We found no difference in mean arterial blood
      pressure between VIP and placebo days but the heart rate increased significantly
      on a VIP day compared with a placebo day (AUC(0-30 min), P < 0.001). Plasma VIP
      was significantly higher on a VIP day compared with placebo (AUC(0-80 min), P <
      0.001). These results show that VIP causes a decrease in V(meanMCA) without
      affecting rCBF. In spite of a marked vasodilator effect in the extracranial
      vessels and increased plasma VIP, healthy subjects developed only a very mild
      headache.

PMID- 16886934
TI  - Blindness and bias in a trial of antidepressant medication for chronic tension
      type headache.
AB  - This study aimed to examine penetration of the blind in a randomized, placebo
      controlled trial. Neurologists' ratings of improvement and medication side
      effects, participants' ratings of improvement and daily diary recordings of
      headaches were assessed along with participants' and neurologists' guesses about
      treatment group placement in participants who completed at least 3 months of
      treatment (N = 169). Despite blinding, treating neurologists successfully
      identified the medication condition for 82% of participants receiving medication
      only; trial participants accurately identified their medication condition when
      receiving active medication (77% of participants), but not when receiving
      placebo. Concurrent stress-management therapy reduced, but did not eliminate
      penetration of the blind. Irrespective of drug condition, when participants were
      improved they were judged to be on active medication and when unimproved they
      were judged to be on placebo. However, neurologists' ratings of improvement,
      participants' reports of improvement and daily headache recordings yielded
      equivalent outcomes. Penetration of the blind needs to be assessed, not assumed
      in clinical trials in headache. However, penetration of the blind did not produce
      a prodrug bias as has been asserted by critics. Better methods of assessing and
      quantifying blindness are needed.

PMID- 16886937
TI  - Imaging abnormalities in sporadic hemiplegic migraine on conventional MRI,
      diffusion and perfusion MRI and MRS.
AB  - Prolonged hemiparetic migraine aura can cause diagnostic confusion and be
      mistaken for ischaemic stroke occurring during the course of a migraine-
      'migrainous infarction'. We report a case of prolonged hemiparesis occurring
      during the course of a migraine attack. Though initially confused with migrainous
      infarction, we suggest with sequential magnetic resonance imaging, magnetic
      resonance angiography, diffusion, perfusion images and magnetic resonance
      spectroscopy that the hemiplegia was not of vascular origin and that the patient
      had sporadic hemiplegic migraine. We hypothesize that the mechanisms of sporadic
      hemiplegic migraine probably lie at a cellular level, similiar to familial
      hemiplegic migraine.

PMID- 16886938
TI  - Tracer clearance in radionuclide cisternography in patients with spontaneous
      intracranial hypotension.
AB  - We semiquantitatively analysed radionuclide cisternography in three patients with
      spontaneous cerebrospinal fluid (CSF) leakage diagnosed by typical symptoms and
      magnetic resonance imaging findings before and several months after treatment
      with epidural blood patch. Radioactivity in the whole CSF space was measured
      immediately after and at 1, 5, 7 and 24 h after intrathecal injection of (111)In
      diethylenetriaminepentaacetic acid (DTPA). Initial findings included the vague
      appearance of leakage in the thoracic spine in two patients, early bladder
      filling at 1 h in one and a lack of tracer filling into the high cranial
      convexity in all three. The radioactivity count rapidly decreased within several
      hours after injection and reached 20% of the initial value at 24 h. In contrast,
      no rapid decrease was observed after treatment and more than 50% of tracer
      remained at 24 h after injection. Semiquantitative analysis of tracer clearance
      may provide additional information in the diagnosis of CSF leakage, especially
      with no obvious qualitative findings.

PMID- 16886939
TI  - Midbrain cavernous malformation causing migraine-like headache.

PMID- 16886940
TI  - Idiopathic intracranial hypertension without headache.

PMID- 16886941
TI  - Secondary cluster headache: a presentation of cerebral venous thrombosis.

PMID- 16886942
TI  - Occipital nerve stimulation for chronic cluster headache and hemicrania continua:
      pain relief and persistence of autonomic features.

PMID- 16886943
TI  - Recurrent coital 'thunderclap' headache associated with ischaemic stroke.

PMID- 16886944
TI  - Pregabalin in the therapy of hypnic headache.

PMID- 16886945
TI  - Late-onset ophthalmoplegic migraine in a patient with previous childhood
      abdominal migraine.

PMID- 16886947
TI  - Intermittent angle-closure glaucoma in the presence of a white eye, posing as
      retinal migraine.

PMID- 16886948
TI  - Sumatriptan causes parallel decrease in plasma CGRP concentration and migraine
      headache during nitroglycerin-induced migraine attack.

PMID- 16886951
TI  - Obesity and polycystic ovary syndrome.
AB  - The aetiology of Polycystic Ovary Syndrome (PCOS) is complex and multifactorial.
      There is much evidence, however, to suggest that adipose tissue plays an
      important role in the development and maintenance of PCOS pathology. There is a
      close correlation between adiposity and symptom severity in women with PCOS, and
      even modest reductions in weight generally translate into significant
      improvements in menstrual regularity, fertility and hyperandrogenic features.
      This review article considers the various mechanisms that might underlie this
      link between excess adiposity and PCOS - including the effects of differential
      insulin sensitivity, abnormal steroid hormone metabolism and adipocytokine
      secretion. Greater attention to the therapeutic options available to reduce the
      impact of excess adiposity on ovarian and metabolic function is essential to the
      management of PCOS.

PMID- 16886952
TI  - Application of new homologous in vitro bioassays for human lactogens to assess
      the actual bioactivity of human prolactin isoforms in hyperprolactinaemic
      patients.
AB  - BACKGROUND: Prolactin (PRL) plays a central role in mammary gland development and
      lactation. Due to its molecular heterogeneity, measurement of PRL
      immunoreactivity does not necessarily reflect its intrinsic bioactivity. For many
      years the Nb2 rat lymphoma cell bioassay has been the only reference bioassay for
      human lactogens. This bioassay, however, does not always correlate with the
      clinical features found in some patients exhibiting normal or elevated
      immunoreactive serum PRL concentrations. OBJECTIVES: (1) To determine the
      concentrations of bioactive PRL in serum samples from individuals with
      normoprolactinaemia or with different forms of hyperprolactinaemia using two
      recently described homologous in vitro bioassays (i.e. a transcriptional bioassay
      in HEK-293 cells and a proliferation assay in Ba/F3 cells); and (2) to compare
      these results with those generated by the classical Nb2 cell bioassay. DESIGN:
      Cross-sectional study. SETTING: An institutional biomedical research laboratory.
      PARTICIPANTS: Ten patients with symptomatic hyperprolactinaemia due to
      prolactinoma, 11 patients with asymptomatic hyperprolactinaemia and
      macroprolactinaemia, and nine normal women. MAIN OUTCOME MEASURES: Measurement of
      immunoreactive and bioactive concentrations of serum PRL. RESULTS: Samples from
      normal women and patients with tumoral hyperprolactinaemia due to prolactinoma
      exhibited similar within-group concentration values of bioactive and
      immunoreactive serum PRL when tested by the three bioassays and the
      immunoradiometric assay employed. By contrast, measurement of bioactive PRL in
      samples from patients with macroprolactinaemia revealed that macroprolactin was
      poorly active in the homologous receptor bioassays, while it was more active in
      the Nb2 bioassay. CONCLUSIONS: The reduced bioactivity of PRL in patients with
      macroprolactinaemia may further explain the absence of clinical features of
      hyperprolactinaemia in these individuals. In addition, our findings indicate that
      species-specificity and sensitivity of the bioassays are determinant factors in
      the measurement of the intrinsic biological activity of circulating PRL.

PMID- 16886953
TI  - Evaluation by magnetic resonance imaging of aortic dilatation and coarctation in
      adult Turner syndrome patients.
AB  - OBJECTIVE: Turner syndrome has well-recognized cardiovascular complications that
      appear in up to 40% of the patients and are more common in monosomy X. Left-sided
      obstructive lesions are relatively more frequent and predispose to aortic root
      dilatation and life-threatening aortic dissection. However, bicuspid aortic
      valves, hypertension, coarctation and aortic stenosis are also at risk of aortic
      dissection. Currently there is no clear guideline regarding the best single test
      for detection or monitoring aortic disease progression. DESIGN: Routine thoracic
      aortic magnetic resonance imaging (MRI) was introduced to the dedicated Turner
      syndrome clinic, with repeated MRI examination every 2 years to detect or assess
      progression of aortic lesions. RESULTS: Seven out of a total of 17 patients
      developed aortic anomalies during the course of surveillance, which included
      coarctation as well as aortic dilatation. None of these patients had any
      cardiovascular symptoms and the vascular abnormalities were detected on MRI at
      presentation or during the course of their follow-up. In patients with previously
      normal aortic imaging, the time interval for the lesion to be detectable varied
      between 2 and 6 years. In one patient there was progression of an established
      lesion over the 2-year period. CONCLUSION: In the few patients presented here,
      regular imaging at first consultation followed by every 2 years would appear to
      be warranted, although the exact frequency of imaging and by what modality still
      need to be ascertained definitively.

PMID- 16886954
TI  - Ghrelin, motilin, insulin concentration in healthy infants in the first months of
      life: relation to fasting time and anthropometry.
AB  - AIMS: This study aimed to investigate: (i) the relation between fasting time and
      serum ghrelin, motilin and insulin concentrations and (ii) the correlations
      between these hormones and anthropometrical parameters of infants in the first 18
      months of life. PATIENT AND METHODS: A cross-sectional study on 62 term infants
      was performed. Blood samples for hormonal assay were obtained at least 1 h after
      feeding. Weight, length and head circumference were recorded. Plasma ghrelin,
      motilin and insulin concentrations were determined by radioimmunoassay. RESULTS:
      Ghrelin and motilin had a significant direct correlation with fasting time (r =
      0.447; P < 0.001 and r = 0.36; P = 0.004, respectively). We observed a negative
      influence of insulin on ghrelin levels (beta = -0.32; P = 0.036). Plasma ghrelin
      levels correlated significantly with age (r = 0.45, P < 0.001), weight (r = 0.31,
      P = 0.013), head circumference (r = 0.35, P = 0.006) and length (r = 0.39, P =
      0.001). A significant correlation emerged between motilin and age (r = 0.45, P <
      0.001), weight (r = 0.43, P = 0.001), head circumference (r = 0.47, P < 0.001)
      and length (r = 0.48, P < 0.001). CONCLUSIONS: Fasting influence on serum ghrelin
      concentration confirms the role of this hormone as a physiological meal initiator
      also in infancy. The correlation between ghrelin, anthropometrical parameters and
      age supports the hypothesis that this hormone could exert an important influence
      on growth in the first months of life. Considering motilin, age and weight might
      play a role in determining its secretion; motilin could be considered one of the
      numerous factors involved in long-term regulation of energy balance.

PMID- 16886955
TI  - Multiple endocrine neoplasia type 1 (MEN 1) is associated with an increased
      prevalence of diabetes mellitus and impaired fasting glucose.
AB  - OBJECTIVE: Multiple endocrine neoplasia type 1 (MEN 1) is an autosomal dominant
      syndrome characterized by primary hyperparathyroidism, pituitary neoplasia and
      foregut lineage neuroendocrine tumours. It has also been associated with
      premature cardiovascular death. As diabetes is a risk factor for increased
      cardiovascular mortality we investigated the prevalence and clinical correlates
      of glycaemic abnormalities in a large MEN 1 kindred. PATIENTS AND DESIGN: The
      glycaemic status of 72 MEN 1 affected and 133 unaffected members of a single
      large MEN 1 pedigree was assessed. Fasting glucose results were categorized and
      compared using WHO criteria. Associations between glycaemic status and MEN 1
      phenotype were assessed. RESULTS: Thirteen (18.1%) patients with MEN 1 compared
      to 5 (3.8%) control patients were diabetic (P < 0.001). Six (8.3%) MEN 1 patients
      had impaired fasting glucose compared to 4 (3%) of controls (P < 0.05). Of
      patients with MEN 1, uncontrolled hypercalcaemia (P < 0.05) and elevated serum
      gastrin (P < 0.05) were more common amongst patients diagnosed with abnormal
      glycaemia than those with normoglycaemia. There was a nonsignificant trend for
      elevated chromogranin A, pancreatic polypeptide, gastric inhibitory polypeptide
      (but not glucagon) and history of bronchopulmonary carcinoid in MEN 1 patients
      with elevated glycaemia. CONCLUSIONS: Diabetes and impaired fasting glucose occur
      significantly more frequently amongst MEN 1 patients than controls and is
      associated with uncontrolled hyperparathyroidism and evidence of enteropancreatic
      hyperstimulation.

PMID- 16886957
TI  - Growth hormone treatment and adverse events in Prader-Willi syndrome: data from
      KIGS (the Pfizer International Growth Database).
AB  - OBJECTIVE: To evaluate the response to recombinant GH treatment and adverse
      events in children with Prader-Willi syndrome (PWS) from KIGS, the Pfizer
      International Growth Database. PATIENTS: A total of 328 children (274
      prepubertal, median age 6.0 years; 54 pubertal, median age 12.7 years) were
      treated for 1 year and 161 children were treated for 2 years with GH. RESULTS:
      Height standard deviation score (SDS) increased significantly during treatment;
      the response was greater in prepubertal (-0.7 vs.-1.8 pretreatment) compared with
      pubertal children (-1.5 vs.-1.8). Predictors of first-year height velocity in
      multiple regression analysis were GH dose, body weight (positively correlated),
      height SDS minus mid-parental height SDS and chronological age (negatively
      correlated), together accounting for 39% of the variation in response to GH. Body
      mass index (BMI) SDS did not change significantly during 2 years of treatment. Of
      all the 675 GH-treated PWS patients in KIGS, there were five cases of sudden
      death (age range 3-15 years). Three were obese (weight for height > 200%) and
      causes of death included bronchopneumonia, respiratory insufficiency and sleep
      apnoea. Scoliosis was the most commonly reported adverse event (n = 24), four
      children developed hyperglycaemia and six had presumptive diabetes (type 2 in
      five, and one case of type 1). CONCLUSIONS: Short-term growth improved in
      response to conventional doses of GH in children with PWS. Prior to commencement
      of GH, examination of the upper airways and sleep studies should be performed in
      PWS patients. GH should be used with caution in those with extreme obesity or
      disordered breathing and all patients should be closely monitored for adverse
      events.

PMID- 16886958
TI  - Phaeochromocytomas presenting as acute crises after beta blockade therapy.
AB  - OBJECTIVE: Phaeochromocytoma crisis is a life-threatening emergency that may be
      undiagnosed because of its numerous, nonspecific manifestations. We analysed,
      retrospectively, the presentation, management and outcome of patients who were
      admitted to our institution with phaeochromocytoma crises over a 5-year period.
      RESULTS: Five patients (two males, three females; mean age 34.6 years, range 19
      51 years) who presented as emergencies requiring intensive care, with multiple
      non-specific manifestations and previously undiagnosed pheochromocytoma, were
      identified. The initial presentation included features of cardiomyopathy (n = 3),
      atypical pneumonia with myocarditis (n = 1) and acute abdomen (n = 1). Only one
      of the five cases had a raised blood pressure at the time of the acute
      presentation. Initiation of beta blockers in four patients was associated with
      further deterioration in haemodynamic status, labile blood pressure and cardiac
      arrhythmias, which led to the diagnosis of the underlying phaeochromocytoma.
      Following intensive supportive therapy and alpha blockade, all five patients
      recovered and underwent elective surgical removal of phaeochromocytoma,
      uneventfully. CONCLUSION: Unexplained cardiopulmonary dysfunction, particularly
      after the institution of beta blockers, should alert clinicians to the
      possibility of phaeochromocytoma. A high index of suspicion is essential to
      reduce morbidity and mortality in these patients through early diagnosis and
      aggressive management.

PMID- 16886959
TI  - Bone mineral density is not reduced in HIV-infected Caucasian men treated with
      highly active antiretroviral therapy.
AB  - OBJECTIVE: Recent studies have reported low bone mineral density (BMD) in
      patients infected with human immunodeficiency virus (HIV). Frequently these
      findings have been attributed to treatment with highly active antiretroviral
      therapy (HAART). We sought to determine whether BMD in HIV-infected men treated
      with HAART for at least 3 months is different from that in healthy controls, and,
      if so, what HIV-related factors might explain this finding. DESIGN: Cross
      sectional analysis. PATIENTS: Fifty-nine HIV-infected Caucasian men treated with
      HAART, and 118 healthy community-dwelling controls. Each HIV-infected man was age
      matched (within 5 years) to two controls. MEASUREMENTS: All participants had
      measurements of BMD and bone-related laboratory parameters. RESULTS: The mean
      duration of known HIV infection was 8.5 years, and of treatment with HAART was 52
      months. There was no significant difference in mean BMD between groups at the
      lumbar spine (HIV group: 1.23 g/cm2, controls: 1.25 g/cm2; P = 0.53) or total
      body (HIV group: 1.18 g/cm2, controls: 1.20 g/cm2; P = 0.09). At the total hip
      the HIV-infected group had significantly lower BMD than the control group (HIV
      group: 1.03 g/cm2, controls: 1.09 g/cm2; P = 0.01). The HIV-infected group were,
      on average, 6.3 kg lighter than the controls. After adjusting for this weight
      difference, HIV infection was not an independent predictor of BMD at any site
      (lumbar spine P = 0.79; total hip P = 0.18; total body P = 0.76). CONCLUSIONS:
      HIV-infected men treated with HAART are lighter than healthy controls. This
      weight difference is responsible for a small decrement in hip BMD. Overall, BMD
      is not significantly reduced in HIV-infected Caucasian men treated with HAART.

PMID- 16886956
TI  - GH peak response to GHRH-arginine: relationship to insulin resistance and other
      cardiovascular risk factors in a population of adults aged 50-90.
AB  - OBJECTIVE: To assess the GH response to GHRH-arginine in apparently healthy
      adults in relation to cardiovascular risk factors. DESIGN: Cross-sectional.
      PATIENTS: Eighty-six male and female volunteers aged 50-90. MEASUREMENTS: GH peak
      response to GHRH-arginine and cardiovascular risk factors, including obesity,
      insulin resistance, low levels of high density lipoprotein (HDL) cholesterol,
      elevated triglycerides, and hypertension. The primary outcome measurement was GH
      response to GHRH-arginine. The relationship between GH peak responses and
      cardiovascular risk factors was determined after data collection. RESULTS: GH
      peaks were highly variable, ranging from 2.3 to 185 microg/l (14% with GH peaks <
      9 microg/l). An increasing number of cardiovascular risk factors were associated
      with a lower mean GH peak (P < 0.0001). By univariate analysis, fasting glucose,
      insulin, body mass index (BMI), HDL cholesterol and triglycerides were
      significantly associated with GH peak (all P < 0.0001). Multiple regression
      analysis revealed that fasting glucose, fasting insulin, BMI, triglycerides and
      sex accounted for 54% of GH peak variability. The role of abdominal fat as it
      relates to GH peak was explored in a subset of 45 subjects. Trunk fat and
      abdominal subregion fat measured by dual energy X-ray absorptiometry (DXA) were
      inversely related to GH peak (P < 0.008 and 0.001, respectively). Analysis of
      this subgroup by multiple regression revealed that subregion abdominal fat became
      the significant obesity-related determinant of GH peak, but still lagged behind
      fasting insulin and glucose. CONCLUSIONS: GH response to secretagogues was highly
      variable in apparently healthy adults aged 50-90 years. Peak GH was significantly
      related to fasting glucose, insulin, BMI, HDL cholesterol, triglycerides, trunk
      fat and abdominal subregion fat, with fasting glucose ranking first by multiple
      regression analysis. There was a strong relationship between cardiovascular risk
      factors and low GH, with individual risk factors being additive. Although these
      data do not differentiate between low GH being a cause or an effect of these
      cardiovascular risk factors, they indicate that the relationship between low GH
      and increased cardiovascular risk may be physiologically important in the absence
      of pituitary disease.

PMID- 16886960
TI  - Identification and functional characterization of three novel human melanocortin
      4 receptor gene variants in an obese Chinese population.
AB  - OBJECTIVE: Mutations in the melanocortin-4 receptor gene (MC4R) are the most
      common monogenic form of human obesity. However, the contribution of MC4R
      mutations to obesity in Chinese has not been investigated. We studied the
      frequency of MC4R mutations in an obese southern Chinese population and the
      functional consequences of the novel variants identified. METHODS: We screened
      for MC4R mutations in 227 obese [body mass index (BMI) 35.29 +/- 5.75 kg/m2] and
      100 lean (BMI 21.57 +/- 0.29 kg/m2) southern Chinese subjects using PCR-direct
      sequencing. In vitro functional studies, including cell surface expression,
      ligand binding, and cyclic adenosine monophosphate (cAMP) accumulation, were
      performed to examine the functional properties of three novel missense mutations.
      RESULTS: Apart from two previously reported polymorphisms, V103I and -176 A > C,
      three novel missense heterozygous variants (Y35C, C40R and M218T) were
      identified. The polymorphisms -176 A > C and Y35C were detected in both obese and
      normal subjects with similar frequency. C40R was identified only in an obese
      subject. Pedigree analysis revealed M218T carriers in both lean and obese
      subjects. The prevalence of V103I carriers in normal-weight controls was
      significantly higher than that in obese subjects (5.3%vs. 1.3%, P < 0.05). In
      vitro functional studies showed that all three novel missense variants have
      normal functions. CONCLUSIONS: Two known polymorphisms and three novel variants
      of the MC4R were identified. No overt functional defects were observed for the
      three novel MC4R variants, suggesting that they might not be the cause of obesity
      in variant carriers.

PMID- 16886961
TI  - Variability of the administered radioiodine doses for the treatment of
      hyperthyroidism in Belgium.
AB  - OBJECTIVE: When using radioiodine for hyperthyroidism there is no consensus
      regarding the administration of fixed or calculated doses. Guidelines do not
      specify the preferable approach or the parameters to use to calculate the dose.
      Therefore, the dose might be quite different with regard to the chosen procedure.
      This study was undertaken to evaluate the variability of the amount of
      radioiodine administered in Belgium in various cases of hyperthyroidism. DESIGN
      AND PATIENTS: Twenty-one Belgian nuclear medicine physicians received summarized
      clinical files from 10 patients suffering from overt hyperthyroidism (n = 7) or
      subclinical hyperthyroidism (n = 3). Five patients had homogeneous goiters, one
      had multinodular goiter, and four had hot nodule. Participants had to determine
      the radioiodine dose (millicuries, mCi) they would give in each case. RESULTS:
      Proposed doses varied between 2 mCi and 25 mCi. Mean proposed dose for nodular
      disease was 10.71 mCi; it was 6.79 mCi for homogeneous goiter. For individual
      cases, a difference between the lowest and the highest dose of more than 17 mCi
      was observed in more than 50% of the cases. CONCLUSIONS: We believe that more
      precise guidelines are mandatory, underlying uncertainties, controversies but
      recommending however, as minimal and maximal doses to administer, as well as
      clinical and biological parameters, if any, to be taken into account in order to
      modulate these doses.

PMID- 16886962
TI  - Serum ghrelin levels are suppressed in hypopituitary patients following insulin
      induced hypoglycaemia irrespective of GH status.
AB  - OBJECTIVE: Circulating ghrelin is suppressed during insulin-induced hypoglycaemia
      in healthy subjects, but it is unknown whether this is determined by feedback
      inhibition from counter-regulatory hormones. We therefore investigated the impact
      of GH and cortisol on ghrelin secretion during insulin-induced hypoglycaemia.
      DESIGN: Serum levels of ghrelin, GH, and cortisol were measured in 41 adult
      patients with suspected hypopituitarism during insulin-induced hypoglycaemia.
      Based on their peak GH response (cut-off level: 3 microg/l), the patients were
      divided into a GH-sufficient group (GHS) and a GH-deficient group (GHD). RESULTS:
      The GHS patients (n = 16) were younger (P < 0.01), had lower baseline cortisol
      levels [255 +/- 37 vs. 372 +/- 38 nmol/l (P = 0.04)], and tended to have a lower
      body mass index (P = 0.09) as compared to GHD patients (n = 25). By definition,
      peak GH (microg/l) was higher in GHS patients [15.0 +/- 1.8 vs. 1.0 +/- 0.2 (P <
      0.0001)]. The increase in serum cortisol during the ITT (insulin-tolerance test)
      was higher and occurred later in GHS patients [Cmax (nmol/l): 561 +/- 41 vs. 412
      +/- 50 (P = 0.04); Tmax (minutes): 65 +/- 5 vs. 49 +/- 5 (P = 0.03)]. Serum
      ghrelin levels changed significantly with time during ITT in both groups (P <
      0.0001), characterized by a moderate decline during the initial 50-60 min and a
      return to baseline after 2 h. No significant differences were recorded in
      AUCghrelin during the ITT between the two groups. No gender differences in
      ghrelin levels were recorded. CONCLUSIONS: (i) Like in healthy subjects serum
      ghrelin levels are suppressed during an ITT in patients with suspected
      hypopituitarism. (ii) The suppression of ghrelin was similar in GHD and GHS
      subjects and was not determined by cortisol. (iii) We hypothesize that insulin
      rather than hypoglycaemia accounts for ghrelin suppression during an ITT.

PMID- 16886963
TI  - Dendritic cells as potential adjuvant for immunotherapy in adrenocortical
      carcinoma.
AB  - OBJECTIVE: Adrenocortical carcinoma (ACC) is a rare malignancy associated with a
      dismal prognosis. Dendritic cells (DCs) are professional antigen-presenting cells
      leading to an antitumour immune response. The aim of this study was to elaborate
      two methods of antigen delivery to DCs and to evaluate an immunotherapy protocol
      in ACC patients. DESIGN/PATIENTS: Autologous DCs were pulsed with autologous
      tumour lysate (TL). Fusion of DCs with tumour cells was based on a polyethylene
      glycol method. Two patients with metastasized hypersecretory ACC were vaccinated
      twice. MEASUREMENTS: In vitro data were quantified by measurement of PBMC
      (peripheral blood mononuclear cell) responses and cytokine secretion and by flow
      cytometry analyses. Clinical response was monitored by CT scan of tumour mass and
      measurement of angiogenic factors. RESULTS: The maximum loading of TL was
      obtained at 24 h as 48.2% (+/- 26.8%) of DCs were TL-positive. The DC/tumour cell
      fusion efficacy was approximately 45% as shown by double positive staining for
      ACTH receptor and DC-specific CD83. In vivo DC vaccination resulted in positive
      delayed-type hypersensitivity skin reactions reflecting specific memory T
      lymphocyte reaction. In vitro analyses revealed specific T-cell proliferation in
      patient 1 (stimulation index: 5.7 compared to pretreatment) and induction of
      cytotoxic granzyme B secreting T cells in patient 2 (0.41% CD8 + cells vs. 0.06%
      pretreatment) as indicators of specific cytotoxic T cells. Although angiogenic
      serum markers could be stabilized, no impact on tumour growth could be observed.
      CONCLUSION: Our data demonstrate that autologous dendritic cells induce antigen
      specific Th1 immunity in adrenocortical carcinoma. The clinical outcome, however,
      was not improved in the patients studied here.

PMID- 16886964
TI  - Metabolic effects of caffeine ingestion and physical work in 75-year old
      citizens. A randomized, double-blind, placebo-controlled, cross-over study.
AB  - OBJECTIVE: Whereas caffeine has been demonstrated to impact substantially on the
      metabolic response to exercise in healthy young subjects, this issue remains to
      be addressed in healthy elderly subjects. DESIGN AND PATIENTS: The metabolic
      response to caffeine ingestion (6 mg/kg) and exercise in healthy elderly citizens
      at 70 years was examined in a randomized, double-blind, placebo-controlled, cross
      over study. We included 30 subjects attending for driver license renewal at their
      general practitioner. Participants abstained from caffeinated drinks and food for
      48 h and were randomized to receive placebo-caffeine or caffeine-placebo with 1
      week between sessions. MEASUREMENTS: A cycling endurance test at 65% of the
      expected maximal heart rate was performed 1 h after intervention. Blood samples
      were taken before intervention, before cycling, after 5 min of cycling, and at
      exhaustion. Analysis was by intention-to-treat and P < 0.05 was regarded as
      significant. RESULTS: Caffeine significantly increased the concentration of
      plasma epinephrine (by 42%, 39%, and 49%), serum-free fatty acids (by 53%, 44%,
      and 50%), and plasma lactate (by 46%, 36%, and 48%), and insulin resistance
      (homeostasis model assessment-IR) (by 21%, 26%, and 23%) during rest, after 5 min
      of cycling, and at exhaustion. At exhaustion, the concentration plasma
      norepinephrine was elevated by 29%. A decrease was seen with caffeine treatment
      in blood potassium after 5 min of cycling and at exhaustion (by 3% and 2%,
      respectively). CONCLUSIONS: Caffeine treatment increased epinephrine, fatty
      acids, lactate and norepinephrine at different times during test session and led
      to insulin-resistance. Hence, caffeine ingestion elicits a similar metabolic
      response in elderly participants at 70 years old to that seen in younger
      subjects.

PMID- 16886966
TI  - Lifestyle factors and forearm bone density in young Greek men.
AB  - OBJECTIVE: The aim of this study was to evaluate the effects of dietary factors
      (calcium, proteins, alcohol, coffee and tea intake), exercise, sunlight exposure
      and immobilization on bone mineral content (BMC) and bone mineral density (BMD)
      in young men. PATIENTS AND MEASUREMENTS: We examined a group of 300 healthy men,
      aged 18-30. Mean weight was 80-81 kg (53-125 kg range) and height 179 cm (160-195
      cm range). Distal BMC (dBMC), distal BMD (dBMD) and ultradistal BMD (udBMD) at
      the radius were measured by single X-ray absorptiometry (Osteometer DTX). The
      data concerning lifestyle factors were obtained through a questionnaire. The 300
      men were divided in four groups according to calcium intake, four groups taking
      into account protein and three groups alcohol intake. There also were five groups
      of exercise level, six groups of sun exposure and two groups of duration of
      immobilization. RESULTS: In the group with the lowest levels of calcium intake (<
      400 mg/day), dBMD and udBMD were lower than in the other groups of calcium intake
      (P = 0.002). dBMC and udBMD were lower (P = 0.043 and 0.015, respectively) in
      subjects with low physical activity (< 2 h/week), whereas dBMC and udBMD were
      higher (P < 0.0005) in subjects with frequent sun exposure (group labelled 'very
      often'). Multiple regression analysis on bone mineral density of the forearm
      showed that, calcium intake, exercise and sunlight were also independent
      predictors of bone mass. No significant correlation between the other examined
      factors and BMD or BMC was detected. CONCLUSIONS: Calcium intake, exercise level
      and sun exposure showed a statistically significant correlation with distal BMD
      and BMC in young adult men.

PMID- 16886965
TI  - Iodine intake and incidence of thyroid cancer in Denmark.
AB  - OBJECTIVE: Iodine intake is suspected to be a risk factor for thyroid cancer.
      Eastern Denmark is characterized by mild and western Denmark by moderate iodine
      deficiency, and this difference is associated with a 50% difference in the
      occurrence of goitre and thyrotoxicosis. The objective of the study was to
      determine whether the incidence of thyroid cancer differs between these two
      regions, as any difference would have important safety implications for the
      national iodine supplementation programme. DESIGN AND METHODS: We studied all
      thyroid cancers notified to the Danish Cancer Registry in the period 1973-1997,
      focusing on the four most frequent subtypes: papillary, follicular, anaplastic
      and medullary thyroid cancer. A Poisson regression model was used with models of
      goodness-of-fit for age, period, sex. RESULTS: No regional difference was found
      in the overall incidence of follicular (0.3% 100 000 person-years) or papillary
      (0.7% 100 000 person-years) thyroid cancer. A slight but nonsignificant increase
      in total incidence, resulting mainly from a significant increase in the incidence
      for the papillary subtype, was observed in both regions. CONCLUSION: The results
      suggest that modest differences in iodine intake do not affect thyroid cancer
      incidence or the distribution of subtypes.

PMID- 16886968
TI  - Characteristics and mortality of severe hyponatraemia--a hospital-based study.
AB  - OBJECTIVE: To determine the characteristics, causes and outcome of severe
      hyponatraemia (< 125 mmol/l) in hospitalized patients, and to identify mortality
      predictors. DESIGN: Prospective case controlled study of sequentially presenting
      patients with a serum sodium (Na) < 125 mmol/l. PATIENTS AND METHODS: One hundred
      and four hyponatraemic and 104 randomly chosen normonatraemic (Na > 135 mmol/l)
      adult patients were studied. We measured hospital mortality and days in hospital,
      diagnoses, drug history and cause of hyponatraemia. Na was recorded at admission,
      as well as the closest level measured before death or discharge. In addition, the
      lowest Na was recorded (if this was not at admission). RESULTS: Hyponatraemic
      patients were older (mean age +/- 1 SD 69 +/- 14 years) than controls (61 +/- 16
      years, P < 0.001), but of similar sex ratio. On admission, Na in the
      hyponatraemic group was 125 +/- 7 mmol/l compared with 139 +/- 3 mmol/l in
      controls (P < 0.0001), but fell to 120 +/- 4 mmol/l before rising at discharge to
      131 +/- 7 mmol/l (all changes P < 0.001). Overall mortality was 27% in
      hyponatraemic patients compared with 9% in controls (P = 0.009), and length of
      admission was also greater (16 +/- 12 vs. 13 +/- 11 days, P < 0.005). Mortality
      was greater in patients whose Na levels fell during admission (34%vs. 16%, P <
      0.05), and these patients appeared to have an excess of diuretic-induced and
      possibly iatrogenic hyponatraemia. CONCLUSIONS: Severe hyponatraemia in hospital
      patients is associated with prolonged admissions and significantly increased
      mortality compared with normonatraemic patients. A particular group at high risk
      of death are those whose Na levels fall after admission. They may represent a
      'sicker' group, and deserve increased monitoring and surveillance.

PMID- 16886967
TI  - Presentation and evolution of organic central precocious puberty according to the
      type of CNS lesion.
AB  - OBJECTIVE: To evaluate the influence of the type and treatment of CNS lesion
      causing central precocious puberty (CPP) on the presentation, hypothalamic
      pituitary function and final height. PATIENTS: One hundred patients with CPP
      caused by central nervous system (CNS) lesion. RESULTS: The CPP was the
      presenting symptom of the lesion in 25 (10 boys) and occurred in 75 patients (23
      boys) previously treated for lesions. These were optic glioma or astrocytoma (n =
      45), hydrocephalus (n = 22), hypothalamic hamartoma (n = 15), suprasellar
      arachnoid cyst (n = 10) and others (n = 8). The percentages of patients with
      increased height, bone age advance, testicular volume, LH/FSH peaks ratio after
      gonadotrophin-releasing hormone (GnRH) test and plasma testosterone concentration
      in boys and oestradiol in girls varied from one aetiology to another. The boys
      with hamartoma were significantly taller and had greater bone age advance, LH
      peak and testosterone than boys with optic glioma. The girls with hamartoma and
      suprasellar arachnoid cyst were significantly younger and had greater LH peak
      than girls in the other groups. All patients treated for optic glioma had
      hypothalamic-pituitary deficiencies, including GH (100%), thyrotrophin (71.4%),
      corticotrophin (12.5%) and pubertal (34.3%) deficiencies. Sixty percent of those
      with suprasellar cysts lacked GH. Final height was below -2 SD in 15/59 (25%)
      patients, including 5/11 not treated with GnRH analogue, 3/5 not treated with GH
      despite GH deficiency, and 2 with hydrocephalus as a result of meningomyelocele.
      CONCLUSIONS: The type of CNS lesion influences the presentation of CPP. This is
      probably caused by differences in the mechanisms inducing puberty and to the
      hypothalamic-pituitary deficiencies associated with the CPP as a result of a
      lesion and/or its treatment.

PMID- 16886969
TI  - Age changes the diagnostic accuracy of mean profile and nadir growth hormone
      levels after oral glucose in postoperative patients with acromegaly.
AB  - BACKGROUND: This analytical, retrospective study was designed to select cut-off
      thresholds of mean GH levels during a diurnal profile and nadir GH levels after
      oral glucose tolerance test (OGTT) according to age to diagnose surgical
      remission of acromegaly. METHODS: One hundred forty-one patients (76 women, aged
      44 +/- 15 years and 65 men, aged 43 +/- 13 years) were included in this study.
      For the purpose of this study, remission was based on insulin-like growth factor
      I (IGF-I) levels in the normal range for age. Diagnostic accuracy was analysed by
      receiving-operator characteristics (ROC) curves in the entire series, and in
      young (20-40 years), middle-aged (41-60 years) and older patients (> 60 years),
      separately. RESULTS: Sixty patients (42.6%) had normal IGF-I levels after
      surgery. In the entire series, in young and in middle-aged patients, the ROC
      analysis showed that optimum cut-off for mean GH levels was 2.3 microg/l
      (diagnostic accuracy range, 94-97%) whereas that for nadir GH after OGTT were,
      respectively, 0.85, 0.9 and 0.8 microg/l (diagnostic accuracy range, 90-95%). In
      the older patients, the optimum cut-off selected for mean GH levels was 1.4
      microg/l and that for nadir GH after OGTT was 0.5 microg/l (diagnostic accuracy,
      100% for both). The comparative analysis of the ROC curves did not show any
      significant difference between mean GH and nadir GH after OGTT (P = 0.21).
      CONCLUSIONS: The criteria currently accepted for diagnosing post-surgical
      remission of acromegaly have high diagnostic accuracy only in the patients aged
      below 60 years. In older patients, lower cut-offs (i.e. = 1.4 microg/l for
      fasting GH and = 0.5 microg/l for nadir GH after OGTT) predict normal IGF-I
      levels. Mean GH levels during a diurnal profile have similar diagnostic accuracy
      of nadir GH levels after OGTT. This suggests that OGTT is not necessary to
      establish surgical cure.

PMID- 16886970
TI  - Resting and exercise energy use in Antarctica: effect of 50% restriction in
      temperate climate energy requirements.
AB  - OBJECTIVE: To determine the impact of energy restriction (ER) upon the previously
      reported increased resting and exercise-related oxygen utilization, reduced body
      temperature, increased serum TSH, and reduced serum free T3 concentrations found
      during Antarctic residence (AR). DESIGN: Prospective, intervention with both
      paired controls and a similar reference control group (RG). PATIENTS AND
      MEASUREMENTS: Seven subjects were assessed before and after a 50% ER period of 60
      h. This ER was carried out within 30 days of arriving in Antarctica in October
      (OCT) and again after 10 months AR in August (AUG). During the periods of ER,
      mean energy consumption was 5662 +/- 1344 kJ/day in OCT and 5529 +/- 967 kJ/day
      in AUG. Resting metabolic rate (RMR), a calculated resting metabolic rate
      (RMR(reg)) using a submaximal work regression, serum TSH, FT3 and tympanic
      temperature (Tty) were measured. These values were compared with a similar RG of
      12 subjects reported previously who were studied in California, USA before and
      then again during AR. RESULTS: Weight declined by 1.1 +/- 0.1 kg/day (OCT) and
      0.92 +/- 0.2 kg/day (AUG) with ER, resulting in a reduction of body weight by 3.1
      +/- 0.4% in OCT (P = 0.0001) and 2.5 +/- 0.4% in AUG (P = 0.0015) during AR. The
      RMR before ER did not change with AR and it was not significantly different from
      the RG studied in California. With ER the RMR tended to decline in both OCT (132
      +/- 5 to 122 +/- 4 mlO2/min/m2) and AUG (134 +/- 5 to 126 +/- 5 mlO2/min/m2), but
      these were not significant. By contrast, RMR(reg) obtained before ER was
      increased with AR by 22.5 +/- 7.8% (P = 0.01) in OCT and by 28.1 +/- 7.0% (P =
      0.0008) in AUG over the RG values obtained in California. RMR(reg) did not
      decrease with ER in either OCT or AUG. The total energy expenditure derived from
      these measures of weight loss suggests that 24-h energy requirements are
      74.4%[95% confidence interval (CI) 2.6-146.3; P < 0.05] more than those expected
      in temperate climates. Tty declined by 0.6 +/- 0.2 degrees C (P < 0.01) with AR
      compared with the RG measured in California, but was not affected by either
      period of ER. ER had no effect on FT3 but tended to decrease serum TSH in AUG (P
      = 0.06). CONCLUSIONS: Exercise-related energy requirements are increased with AR.
      Moderate ER may reduce resting but not exercise-related energy expenditure and it
      is associated with a weight loss exceeding expectations for 50% restriction of
      temperate climate energy predictions.

PMID- 16886971
TI  - Guidelines of the Pituitary Society for the diagnosis and management of
      prolactinomas.
AB  - In June 2005, an ad hoc Expert Committee formed by the Pituitary Society convened
      during the 9th International Pituitary Congress in San Diego, California. Members
      of this committee consisted of invited international experts in the field, and
      included endocrinologists and neurosurgeons with recognized expertise in the
      management of prolactinomas. Discussions were held that included all interested
      participants to the Congress and resulted in formulation of these guidelines,
      which represent the current recommendations on the diagnosis and management of
      prolactinomas based upon comprehensive analysis and synthesis of all available
      data.

PMID- 16886972
TI  - We live in the age of the clinical guideline.

PMID- 16886973
TI  - ILAE treatment guidelines: evidence-based analysis of antiepileptic drug efficacy
      and effectiveness as initial monotherapy for epileptic seizures and syndromes.
AB  - PURPOSE: To assess which antiepileptic medications (AEDs) have the best evidence
      for long-term efficacy or effectiveness as initial monotherapy for patients with
      newly diagnosed or untreated epilepsy. METHODS: A 10-member subcommission of the
      Commission on Therapeutic Strategies of The International League Against Epilepsy
      (ILAE), including adult and pediatric epileptologists, clinical pharmacologists,
      clinical trialists, and a statistician evaluated available evidence found through
      a structured literature review including MEDLINE, Current Contents and the
      Cochrane Library for all applicable articles from 1940 until July 2005. Articles
      dealing with different seizure types (for different age groups) and two epilepsy
      syndromes were assessed for quality of evidence (four classes) based on
      predefined criteria. Criteria for class I classification were a double-blind
      randomized controlled trial (RCT) design, >or=48-week treatment duration without
      forced exit criteria, information on >or=24-week seizure freedom data (efficacy)
      or >or=48-week retention data (effectiveness), demonstration of superiority or
      80% power to detect a <or=20% relative difference in efficacy/effectiveness
      versus an adequate comparator, and appropriate statistical analysis. Class II
      studies met all class I criteria except for having either treatment duration of
      24 to 47 weeks or, for noninferiority analysis, a power to only exclude a 21-30%
      relative difference. Class III studies included other randomized double-blind and
      open-label trials, and class IV included other forms of evidence (e.g., expert
      opinion, case reports). Quality of clinical trial evidence was used to determine
      the strength of the level of recommendation. RESULTS: A total of 50 RCTs and
      seven meta-analyses contributed to the analysis. Only four RCTs had class I
      evidence, whereas two had class II evidence; the remainder were evaluated as
      class III evidence. Three seizure types had AEDs with level A or level B efficacy
      and effectiveness evidence as initial monotherapy: adults with partial-onset
      seizures (level A, carbamazepine and phenytoin; level B, valproic acid), children
      with partial-onset seizures (level A, oxcarbazepine; level B, None), and elderly
      adults with partial-onset seizures (level A, gabapentin and lamotrigine; level B,
      None). One adult seizure type [adults with generalized-onset tonic-clonic (GTC)
      seizures], two pediatric seizure types (GTC seizures and absence seizures), and
      two epilepsy syndromes (benign epilepsy with centrotemporal spikes and juvenile
      myoclonic epilepsy) had no AEDs with level A or level B efficacy and
      effectiveness evidence as initial monotherapy. CONCLUSIONS: This evidence-based
      guideline focused on AED efficacy or effectiveness as initial monotherapy for
      patients with newly diagnosed or untreated epilepsy. The absence of rigorous
      comprehensive adverse effects data makes it impossible to develop an evidence
      based guideline aimed at identifying the overall optimal recommended initial
      monotherapy AED. There is an especially alarming lack of well-designed, properly
      conducted RCTs for patients with generalized seizures/epilepsies and for children
      in general. The majority of relevant existing RCTs have significant methodologic
      problems that limit their applicability to this guideline's clinically relevant
      main question. Multicenter, multinational efforts are needed to design, conduct
      and analyze future clinically relevant RCTs that can answer the many outstanding
      questions identified in this guideline. The ultimate choice of an AED for any
      individual patient with newly diagnosed or untreated epilepsy should include
      consideration of the strength of the efficacy and effectiveness evidence for each
      AED along with other variables such as the AED safety and tolerability profile,
      pharmacokinetic properties, formulations, and expense. When selecting a patient's
      AED, physicians and patients should consider all relevant variables and not just
      efficacy and effectiveness.

PMID- 16886974
TI  - Comparison of the cognitive effects of tiagabine and carbamazepine as monotherapy
      in newly diagnosed adult patients with partial epilepsy: pooled analysis of two
      long-term, randomized, follow-up studies.
AB  - PURPOSE: Patients with epilepsy are at greater risk for cognitive impairment than
      are age- and education-matched controls. Cognitive decline is a significant
      adverse event associated with many first-generation anticonvulsant drugs (AEDs);
      however, the past decade has seen the introduction of several new AEDs with more
      favorable cognitive profiles. Tiagabine (TGB) is indicated as adjunctive therapy
      for the treatment of partial seizures. The cognitive effects of TGB and
      carbamazepine (CBZ) monotherapy were evaluated in adult epilepsy patients with
      partial seizures. METHODS: This analysis pooled data from two randomized studies
      with similar populations, dosing, and cognitive assessments. TGB was titrated to
      20-30 mg/day and CBZ to 400-800 mg/day over a 6-week period. A control or no-drug
      group of untreated patients with a single epileptic seizure was included for
      comparison. Cognitive function was assessed at baseline and 52 weeks. RESULTS: Of
      the 105 epilepsy patients enrolled, 79 completed the 52 weeks of monotherapy
      (TGB, 74%; CBZ, 77%). Altogether, 19 untreated patients composed the no-drug
      group. During the 52-week follow-up, only one statistically significant
      difference was found between the treatment groups and the no-drug group [verbal
      fluency task: F(2, 92) = 3.16; p = 0.047]. On further analysis, it was determined
      that this statistical difference was solely based on the patients receiving CBZ
      performing worse than the control group (p = 0.048). Statistically significant
      improvements (p < 0.05) were found on six (26%) of 23 variables with TGB and CBZ,
      as well as the no-drug group, although the variables differed between the groups.
      Significant worsening in the test scores was not seen in any of the study groups.
      CONCLUSIONS: The results of this 52-week, follow-up study show that successful
      TGB monotherapy with 20-30 mg/day has a cognitive profile similar to that of
      successful long-term CBZ monotherapy with 400-800 mg/day in newly diagnosed
      patients with epilepsy and to that of untreated patients with a single seizure.
      We observed no significant decline in cognitive scores associated with TGB
      monotherapy.

PMID- 16886975
TI  - Levetiracetam intravenous infusion: a randomized, placebo-controlled safety and
      pharmacokinetic study.
AB  - PURPOSE: The primary objective of this placebo-controlled study was to evaluate
      the safety and tolerability of levetiracetam (LEV) administered intravenously
      (IV) at higher doses and/or at a faster infusion rate than proposed. The
      secondary objective was to assess LEV pharmacokinetics. METHODS: Single ascending
      doses of LEV administered by IV infusion (2,000, 3,000, 4,000 mg over 15 min;
      1,500, 2,000, 2,500 mg over 5 min) were evaluated in 48 healthy subjects in a
      randomized, single-blind, placebo-controlled study. RESULTS: All randomized
      subjects completed the study. Adverse events reported after IV administration of
      LEV (<or=4,000 mg infused over 15 min and <or=2,500 mg infused over 5 min) were
      primarily related to the CNS (dizziness, 52.8%; somnolence, 33.3%; fatigue,
      11.1%; headache, 8.3%) and were consistent with the established safety profile
      for the oral formulation. Safety profiles were similar for each dose level of LEV
      and for both IV infusion rates, with no clear relation noted between incidence of
      adverse events and IV dose level or infusion rate. The pharmacokinetics of LEV
      administered by IV infusion was comparable across all dose groups and infusion
      rates. Respective geometric means (coefficient of variation) for 4,000 mg
      administered over 15 min and 2,500 mg infused over 5 min were maximum plasma
      concentration, 145 (24.6%) and 94.3 (36.2%) mug/ml; area under the plasma
      concentration-time curve, 1,239 (19.2%) and 585 (9.6%) mug/h/ml; terminal half
      life, 8.0 (14.5%) and 7.0 (12.7%) h. CONCLUSIONS: LEV administered by IV infusion
      at dosages and/or infusion rates higher than those proposed was well tolerated in
      healthy subjects, and the pharmacokinetic profile was consistent with that for
      LEV administered orally.

PMID- 16886976
TI  - Valproate-associated coagulopathies are frequent and variable in children.
AB  - PURPOSE: Valproic acid (VPA) is an antiepileptic drug (AED) commonly used for
      generalized and focal epilepsies. The clinical relevance of coagulopathies, known
      as side effects of VPA therapy, especially thrombocytopenia, von Willebrand
      disease, and a decrease of factor XIII, is still unclear. METHODS: In our
      institute, we noticed a high incidence of clinically relevant coagulation
      problems related to VPA in eight patients within 1 year only and a further seven
      children with significant coagulopathy were identified in the context of planned
      surgery. RESULTS: We provide an overview of these patients and all six VPA
      induced coagulopathies. CONCLUSIONS: At this time, it cannot be recommended to
      control all hemostatic parameters in every patient. Whenever an increased
      bleeding tendency is observed, or before surgical procedures, a platelet count,
      thrombelastography, prothrombin time, activated partial thromboplastin time, TT,
      fibrinogen, von Willebrand factor, and factor XIII should be examined. With 385
      VPA-treated patients per year and 15 cases of coagulation disorders in this
      period, we estimate the incidence of coagulation disorders related to VPA in
      children to be nearly 4%.

PMID- 16886977
TI  - Neocortical hyperexcitability in a genetic model of absence seizures and its
      reduction by levetiracetam.
AB  - PURPOSE: To study the effect of the antiepileptic drug levetiracetam (LEV) on the
      patterns of intrinsic optical signals (IOSs) generated by slices of the
      somatosensory cortex obtained from 3- and 6-month-old WAG/Rij and age-matched,
      nonepileptic control (NEC) rats. METHODS: WAG/Rij and NEC animals were
      anesthetized with enfluorane and decapitated. Brains were quickly removed, and
      neocortical slices were cut coronally with a vibratome, transferred to a
      submerged tissue chamber, and superfused with oxygenated artificial cerebrospinal
      fluid (aCSF). Slices were illuminated with a dark-field condensor and examined
      with a x2.5 objective; images were processed with a real time digital video image
      enhancement system. Images were acquired before (background) and during
      electrical stimulation with a temporal resolution of 10 images/s and were
      displayed in pseudocolors. Extracellular stimuli (200 micros; <4 V) were
      delivered through bipolar stainless steel electrodes placed in the white matter.
      RESULTS: IOSs recorded in NEC slices bathed in control aCSF became less intense
      and of reduced size with age (p < 0.05); this trend was not seen in WAG/Rij
      slices. Age-dependent decreases in IOS intensity and area size were also seen in
      NEC slices superfused with aCSF containing the convulsant 4-aminopyridine (4-AP,
      5 microM); in contrast, significant increases in both parameters occurred with
      age in 4-AP-treated WAG/Rij slices (p < 0.05). Under any of these conditions, the
      IOS intensity and area size slices were larger in WAG/Rij than in NEC slices. LEV
      (50-500 microM) application to WAG/Rij slices caused dose-dependent IOS
      reductions that were evident both in control and in 4-AP-containing aCSF and were
      more pronounced in 6-month-old tissue. CONCLUSIONS: These data demonstrate age
      dependent IOS modifications in NEC and WAG/Rij rat slices and identify a clear
      pattern of hyperexcitability that occurs in 6-month-old WAG/Rij neocortical
      tissue, an age when absence seizures occur in all animals. The ability of LEV to
      reduce these patterns of network hyperexcitability supports the potential use of
      this new antiepileptic drug in primary generalized epileptic disorders.

PMID- 16886978
TI  - The effect of the new antiepileptic drug rufinamide on cognitive functions.
AB  - PURPOSE: Rufinamide (RUF 331; 1-(2,6-difluoro-phenyl)methyl-1H-1,2,3-triazole-4
      carboxamide) is a structurally novel compound that limits the frequency of sodium
      dependent neuronal action potentials. So far no data have been published on the
      cognitive effects of RUF, except for two animal studies. METHODS: The study used
      a multicenter, multinational double-blind, randomized, placebo-controlled
      parallel-study design with four different doses of RUF (based on prior studies):
      200 mg/day, 400 mg/day, 800 mg/day, and 1,600 mg/day as add-on to the existing
      medication. All patients had partial seizures, in the age range of 15-64 years
      (with an average of 37.5 years). Cognitive assessments were performed at baseline
      (before the start with RUF treatment) and at end point (after 3 months of
      treatment). RESULTS: In total, 189 patients were included, divided over the
      treatment groups: placebo (n = 41), 200 mg/day (n = 33), 400 mg/day (n = 38), 800
      mg/day (n = 37), and 1,600 mg/day (n = 40). The most important finding is that
      for none of the cognitive tests did a statistically significant worsening occur
      for any of the doses of RUF when the period after 12 weeks of treatment was
      compared with the baseline before introducing RUF. Also none of the comparisons
      between dose and placebo showed a statistically significant difference.
      CONCLUSIONS: RUF is a new AED with no serious cognitive effects even in add-on
      treatment and even in the higher dose ranges.

PMID- 16886979
TI  - Inactivation of caspase-1 in rodent brain: a novel anticonvulsive strategy.
AB  - PURPOSE: Cytokines and related inflammatory mediators are rapidly synthesized in
      the brain during seizures. We previously found that intracerebral administration
      of interleukin-1 (IL-1)-beta has proconvulsant effects, whereas its endogenous
      receptor antagonist (IL-1Ra) mediates potent anticonvulsant actions in various
      models of limbic seizures. In this study, we investigated whether seizures can be
      effectively inhibited by blocking the brain production of IL-1beta, by using
      selective inhibitors of interleukin-converting enzyme (ICE/caspase-1) or through
      caspase-1 gene deletion. METHODS: Caspase-1 was selectively blocked by using
      pralnacasan or VX-765. IL-1beta release was induced in mouse organotypic
      hippocampal slice cultures by proinflammatory stimuli [lipopolysaccharide (LPS) +
      adenosine triphosphate (ATP)] and measured with enzyme-linked immunosorbent assay
      (ELISA). IL-1beta production during seizures was measured in the rat hippocampus
      by Western blot. Seizures were induced in freely moving mice and rats by
      intrahippocampal injection of kainic acid and recorded by EEG analysis. RESULTS:
      Caspase-1 inhibition reduced the release of IL-1beta in organotypic slices
      exposed to LPS+ATP. Administration of pralnacasan (intracerebroventricular, 50
      microg) or VX-765 (intraperitoneal, 25-200 mg/kg) to rats blocked seizure-induced
      production of IL-1beta in the hippocampus, and resulted in a twofold delay in
      seizure onset and 50% reduction in seizure duration. Mice with caspase-1 gene
      deletion showed a 70% reduction in seizures and an approximate fourfold delay in
      their onset. CONCLUSIONS: Inhibition of caspase-1 represents an effective and
      novel anticonvulsive strategy, which acts by selectively reducing the brain
      availability of IL-1beta.

PMID- 16886981
TI  - Sleep disturbances reported by refractory partial-onset epilepsy patients
      receiving polytherapy.
AB  - PURPOSE: Although sleep disturbances are common in epilepsy, few studies examined
      the prevalence and impact of sleep disturbance in epilepsy patients. This study
      investigates these in a cross-sectional survey. METHODS: We surveyed 201 adult
      partial-onset epilepsy patients taking stable regimens of two or more
      antiepileptic medications. Community-based U.S. neurologists recorded patient
      demographic and clinical information. Patients completed the Medical Outcomes
      Study (MOS) Sleep Scale, the Quality of Life in Epilepsy-10 instrument (QOLIE
      10), and the EuroQol-5D (EQ-5D). We evaluated the associations of sleep with
      health-related quality of life and clinical and demographic characteristics by
      using correlation coefficients and analysis of variance. RESULTS: Mean (SD) age
      was 44.2 (12.5); 34% of patients had diagnosed sleep disturbances; 10% received
      prescription sleep medications. Patients with sleep disturbance reported poorer
      mean QOLIE-10 (55.2 vs. 63.7; p = 0.006) and EQ-5D (0.49 vs. 0.71; p < 0.001)
      scores relative to those without sleep disturbances. The mean (SD) MOS Sleep
      Problems Index score was 36.2 (20.8), worse than the general population mean of
      26. Patients with physician-reported anxiety or depression had more sleep
      problems than did those without these comorbidities. Higher Sleep Problems Index
      scores were significantly (p < 0.001) correlated with poorer QOLIE-10 (r=-0.49)
      and EQ-5D (r=-0.56) scores. Patients experiencing a seizure within the past week
      reported higher MOS Sleep Problems Index scores than did those with a less-recent
      seizure (41.5 vs. 32.8; p = 0.003). CONCLUSIONS: Diagnosed and self-reported
      sleep disturbances in patients with partial-onset epilepsy are frequently
      overlooked, but are negatively associated with everyday functioning and well
      being, and therefore contribute significantly to the burden of epilepsy.

PMID- 16886980
TI  - Antiepileptic effect of gap-junction blockers in a rat model of refractory focal
      cortical epilepsy.
AB  - PURPOSE: Epilepsy is the most common serious neurologic disease, and current
      treatments are ineffective for <or=30% of patients. Gap junctions have been
      implicated in seizure generation and propagation, and as such, may represent a
      novel therapeutic target but have been little investigated in vivo. We set out to
      assess the efficacy and tolerability of gap-junction blockers delivered to the
      seizure focus in a well-characterized model of refractory cortical epilepsy in
      rats. METHODS: A chronic epilepsy focus was induced in the cortex of rats by
      using tetanus toxin, and subsequent studies were conducted in freely moving
      unanesthetized animals with frequent spontaneous seizures, as we previously
      described. Carbenoxolone, meclofenamic acid, and saline were applied directly to
      the seizure focus. EEG, electromyogram (EMG), and behavioral parameters were
      measured for >or=1 h before drug infusion and for >or=3 h afterward. No ill
      effects were observed. RESULTS: An immediate and marked reduction in percentage
      of seizure time was seen in rats receiving carbenoxolone (baseline, 69.4%+/- 7.0%
      (SEM); maximum effect, 9.3%+/- 3.5%, p <or=0.001) and meclofenamic acid
      (baseline, 58.3%+/- 3.7%; maximum effect, 0.92%+/- 0.92%, p < 0.001). No effect
      was seen after saline infusion. CONCLUSIONS: Gap-junction blockers applied
      focally are effective at suppressing seizures and, as such, represent a potential
      new treatment for epilepsy. Development of focal treatment strategies is
      essential in this regard.

PMID- 16886982
TI  - Efficacy and safety of radiosurgical callosotomy: a retrospective analysis.
AB  - PURPOSE: Anterior callosotomy is a surgical option for the treatment of
      generalized tonic or atonic seizures associated with drop attacks. Besides open
      surgery, a radiosurgical callosal disconnection using the gamma knife (GK) also
      can be performed, but reliable data about tolerability and efficacy are sparse.
      METHODS: Eight patients (three female, five male age range, 5 to 69 years) with
      severe generalized epilepsy associated with disabling drop attacks underwent GK
      callosotomy between 1993 and 2004. In six patients, the anterior third of the
      corpus callosum was radiosurgically disconnected. In one patient a second
      procedure with GK treatment of the middle third of the corpus callosum was added
      17 months later. In two patients posterior GK callosotomy had followed partial
      hemispherotomy. RESULTS: Drop attacks (DAs) were completely abolished in three
      patients, and two patients had a marked DA seizure reduction of 60%. Two of four
      patients with additional generalized tonic-clonic seizures showed a reduction of
      100%, and the remaining, a 50% and 60% decrease, respectively. Other seizure
      types responded less well to the radiosurgical treatment. In both patients with
      posterior GK callosotomy after hemispherotomy, partial seizures decreased. Beside
      transient headache in two patients, no immediate or long-term postradiosurgical
      side effects were observed. CONCLUSIONS: Palliative radiosurgical callosotomy is
      an efficient and safe noninvasive alternative to the open procedure with
      comparable results. No signs of postradiosurgical side effects were noted within
      an up to 12-year posttreatment period.

PMID- 16886983
TI  - Transcallosal resection of hypothalamic hamartoma for intractable epilepsy.
AB  - PURPOSE: To present the results of transcallosal surgical resection of
      hypothalamic hamartoma (HH) in 26 patients with refractory epilepsy in a
      prospective outcome study. METHODS: Patients with refractory epilepsy symptomatic
      to HH were referred for surgical resection of their HH (mean age, 10.0 years;
      range, 2.1-24.2 years). A transcallosal, interforniceal approach was used to
      remove and/or disconnect the hamartoma. Volumetry was obtained on pre- and
      postoperative brain MRI scans to determine percentage of resection. Outcome
      assessment included determination of postoperative seizure frequencies in
      comparison to baseline and the incidence of postoperative complications.
      Postoperative changes in cognitive and behavioral functioning, in comparison to
      baseline, were elicited by parental report. RESULTS: The average postoperative
      follow-up interval was 20.3 months (range, 13-28 months). Fourteen (54%) patients
      were completely seizure free, and nine (35%) had at least a 90% improvement in
      total seizure frequency. Parents reported postoperative improvement in behavior
      in 23 (88%) patients and in cognition in 17 (65%) patients. Transient
      postoperative memory disturbance was seen in 15 (58%) patients, but persisted in
      only two (8%). Two (8%) patients had persisting endocrine disturbance requiring
      hormone replacement therapy (diabetes insipidus and hypothyroidism in one each).
      With univariate analysis, the likelihood of a seizure-free outcome correlated
      with younger age, shorter lifetime duration of epilepsy, smaller preoperative HH
      volume, and 100% HH resection. CONCLUSIONS: Refractory epilepsy associated with
      HH can be safely and effectively treated with surgical resection by a
      transcallosal, interforniceal approach. Short-term memory deficits appear to be
      transient for most patients, and family perception of the impact of surgery on
      cognitive and behavioral domains is favorable. Complete resection yields the best
      result.

PMID- 16886984
TI  - Neuromodulation of the centromedian thalamic nuclei in the treatment of
      generalized seizures and the improvement of the quality of life in patients with
      Lennox-Gastaut syndrome.
AB  - PURPOSE: Our aim was to evaluate the efficacy of ESCM (electrical stimulation of
      the centromedian thalamic nucleus) in treatment of generalized seizures of the
      Lennox-Gastaut syndrome (LGS) and improvement of patient disability. METHODS:
      Thirteen patients with LGS were studied. They had severe generalized tonic-clonic
      seizures (GTC) and atypical absences (AA). All patients had at least a 6-month
      baseline before bilateral electrode implantation to the centromedian (CM) nuclei
      of the thalamus to undergo therapeutic ESCM. Once implanted, electrodes were
      temporally externalized through a retromastoid point for electrophysiologic
      confirmation of their placement. After target confirmation, stimulation
      parameters were set. Patients came for follow-up assessment of seizures and
      neurophysiologic tests every 3 months during an 18-month period of time; AED
      therapy was not modified. RESULTS: The surgical procedure as well as electrical
      stimulation was well tolerated by all patients. No side effects occurred with the
      therapeutic stimulation parameters used, and patients were not aware of device
      activation. Two patients were explanted because of repeated and multiple skin
      erosions that could not be controlled by plastic surgery procedures. Overall
      seizure reduction was 80%. The three patients with poorest outcomes for seizure
      control did not improve their ability scale score. In contrast, the two patients
      rendered seizure free are living a normal life at present. The remaining eight
      patients experienced progressive improvement, from being totally disabled to
      becoming independent in five cases and partially dependent in two. Patients with
      adequate electrode placement had a seizure reduction >87%. To consider that an
      electrode is correctly placed, both stereotactic placement and neurophysiologic
      responses are taken into account. CONCLUSIONS: ESCM provides a nonlesional,
      neuromodulatory method with improvement in seizure outcome and in the abilities
      of patients with severe LGS.

PMID- 16886985
TI  - Pilot study of trigeminal nerve stimulation (TNS) for epilepsy: a proof-of
      concept trial.
AB  - The safety and preliminary efficacy of trigeminal nerve stimulation (TNS) for
      epilepsy was evaluated in a pilot feasibility study of transcutaneous stimulation
      of the infraorbital and supraorbital branches of the trigeminal nerve. TNS was
      well tolerated. Four (57%) of seven subjects who completed >or=3 months
      experienced a >or=50% reduction in seizure frequency. The results of this pilot
      study support further investigation into the safety and efficacy of TNS for
      epilepsy.

PMID- 16886986
TI  - Anticonvulsant effects of transcranial direct-current stimulation (tDCS) in the
      rat cortical ramp model of focal epilepsy.
AB  - PURPOSE: Weak direct currents induce lasting alterations of cortical excitability
      in animals and humans, which are controlled by polarity, duration of stimulation,
      and current strength applied. To evaluate its anticonvulsant potential,
      transcranial direct current stimulation (tDCS) was tested in a modified cortical
      ramp-stimulation model of focal epilepsy. METHODS: The threshold for localized
      seizure activity (TLS) was determined in freely moving rats by applying a single
      train of rising bipolar pulses through a unilateral epicranial electrode. After
      tDCS, TLS was determined repeatedly for 120 min at intervals of 15 min. The first
      group of animals received two sessions of cathodal tDCS at 100 microA, one for 30
      and one for 60 min. A third session consisted of 60 min of anodal tDCS. A second
      group received cathodal tDCS at 200 microA for 15 and for 30 min, as well as
      anodal tDCS for 30 min. RESULTS: Sixty minutes of cathodal tDCS at 100 microA
      resulted in a TLS increase lasting for >or=2 h. When the intensity was increased
      to 200 microA, a similar lasting TLS elevation occurred after a stimulation of
      just 30-min duration. In contrast, anodal tDCS at identical stimulation durations
      and current strengths had no significant effect on TLS. CONCLUSIONS: The
      anticonvulsive effect induced by cathodal tDCS depends on stimulation duration
      and current strength and may be associated with the induction of alterations of
      cortical excitability that outlast the actual stimulation. The results lead to
      the reasonable assumption that cathodal tDCS could evolve as a therapeutic tool
      in drug-refractory partial epilepsy.

PMID- 16886987
TI  - Epilepsy Care in the World: results of an ILAE/IBE/WHO Global Campaign Against
      Epilepsy survey.
AB  - PURPOSE: Information about existing resources available within the countries to
      tackle the huge medical, social, and economic burden caused by epilepsy is
      lacking. To fill this information gap, a survey of country resources available
      for epilepsy care was conducted within the framework of the ILAE/IBE/WHO Global
      Campaign Against Epilepsy. METHODS: The study represents a major collaborative
      effort involving the World Health Organization (WHO), the International League
      Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE). RESULTS:
      Data were collected from 160 countries representing 97.5% of the world
      population. The information included availability, role, and involvement of
      professional and patient associations for epilepsy, epilepsy treatment and
      services including antiepileptic drugs, human resources involved in epilepsy
      care, teaching in epileptology, disability benefits, and problems encountered by
      people with epilepsy and health professionals involved in epilepsy care. The data
      confirm that epilepsy care is grossly inadequate compared with the needs in most
      countries. In addition, large inequities exist across regions and income groups
      of countries, with low-income countries having extremely meager resources.
      Complete results of this survey can be found in the Atlas: Epilepsy Care in the
      World. CONCLUSIONS: The data reinforce the need for urgent, substantial, and
      systematic action to enhance resources for epilepsy care, especially in low
      income countries.

PMID- 16886988
TI  - Risk of aplastic anemia in patients using antiepileptic drugs.
AB  - PURPOSE: To assess the association between exposure to antiepileptic drugs (AEDs)
      and the occurrence of aplastic anemia. METHODS: A retrospective case-control
      study was conducted using data from the U.K. General Practitioners Research
      Database (GPRD). Cases were defined as patients diagnosed with aplastic anemia.
      For each case, up to three control patients were matched on age, sex, and medical
      practice. Cases and controls were compared with respect to AED use. The effects
      of duration of AED use were assessed. Characteristics of individual cases with
      AED use were reviewed. RESULTS: The study population comprised 173 cases and 497
      controls. AED use was more prevalent among cases (9.2%) than among controls
      (0.8%). After adjustment for confounders, the use of AEDs was significantly
      associated with aplastic anemia (adjusted odds ratio (OR), 9.5; 95% confidence
      interval (CI), 3.0-39.7). The most frequently used AEDs were carbamazepine (CBZ),
      valproic acid (VPA), and phenytoin. The 16 exposed cases were heterogeneous with
      respect to patient and exposure characteristics: the age of these patients varied
      from 1 to 92 years, and the duration of AED use varied from 17 days to 6.8 years.
      CONCLUSIONS: This study indicates that use of AEDs, in particular CBZ and VPA, is
      associated with a ninefold increased risk of aplastic anemia. Physicians should
      be alert to the possibility of AED-associated aplastic anemia.

PMID- 16886989
TI  - Temozolomide treatment of refractory epilepsy in a patient with an
      oligodendroglioma.
AB  - A 40-year-old man with a left frontotemporal grade II oligodendroglioma developed
      seizures that were refractory to 14 antiepileptic medications, the ketogenic
      diet, and epilepsy surgery. With temozolomide therapy, his seizure frequency
      gradually changed from 30 partial seizures per day to a single simple partial
      seizure in 6 months. No additional therapeutic measures were introduced during
      this time. This reduction in seizure frequency appears attributable solely to
      temozolomide therapy.

PMID- 16886990
TI  - Deep brain stimulation of the subthalamic nucleus as adjunct treatment for
      refractory epilepsy.
AB  - PURPOSE: We studied the efficacy and safety of bilateral subthalamic deep brain
      stimulation (DBS) for refractory partial-onset epilepsy in two cases. METHODS:
      This was an open treatment pilot study for subjects who had failed numerous
      medications and had seizure injuries. Seizure counts and adverse events were
      collected during a 3-4 month baseline, and for 26-32 months after DBS surgery,
      with AEDs held constant. RESULTS: Case 1, age 45, with bitemporal seizures, had
      about half the seizure frequency but still fell with injuries. Case 2, age 46,
      with left frontal encephalomalacia, had a frequency reduction of about one-third,
      but a more meaningful reduction of seizure severity and injuries. CONCLUSIONS:
      Subthalamic DBS partly reduced partial-onset seizures, but the quality of life
      was more affected by seizure-related injuries.

PMID- 16886991
TI  - Double-blind, randomized controlled study of bilateral cerebellar stimulation.

PMID- 16886994
TI  - Integration of structural and functional genomics.
AB  - This paper introduces a special issue of Animal Genetics, which is devoted to the
      recent symposium held at Iowa State University entitled 'Integration of
      Structural and Functional Genomics'. We describe issues and needs that confront
      the animal genomics community, and describe how this symposium was structured to
      address these issues by improving communication and collaboration across species
      and disciplines. The session topics and oral presentations are briefly described
      for all invited speakers.

PMID- 16886995
TI  - An integrative approach for the identification of quantitative trait loci.
AB  - The genetic dissection of complex traits is one of the most difficult and most
      important challenges facing science today. We discuss here an integrative
      approach to quantitative trait loci (QTL) mapping in mice. This approach makes
      use of the wealth of genetic tools available in mice, as well as the recent
      advances in genome sequence data already available for a number of inbred mouse
      strains. We have developed mapping strategies that allow a stepwise narrowing of
      a QTL mapping interval, prioritizing candidate genes for further analysis with
      the potential of identifying the most probable candidate gene for the given
      trait. This approach integrates traditional mapping tools, fine mapping tools,
      sequence-based analysis, bioinformatics and gene expression.

PMID- 16886996
TI  - Genetical genomics in livestock: potentials and pitfalls.
AB  - Genetical genomics combines gene mapping and gene expression approaches to
      identify loci controlling gene expression (eQTLs) that may underlie functional
      trait variation. The combination of genomic tools has great potential to
      facilitate dissection of complex traits, but studies need careful design and
      interpretation. Here we explore both the potential and the pitfalls of this
      approach with illustrations from actual studies. There are now an appreciable
      number of studies in model species and even humans demonstrating the feasibility
      of genetical genomics. However, most studies are too limited in size and design
      to unlock the full potential of the approach. Limited statistical power of
      studies exacerbates the problem of detection of false-positive eQTL and some
      reported results should be interpreted with caution. As one approach to more
      successful implementation of genetical genomics, we propose to combine expression
      studies with fine mapping of functional trait loci. This synergistic approach
      facilitates the implementation of genetical genomics for species without inbred
      resources but is equally applicable to model species. These properties make it
      particularly suitable for livestock populations where many QTL are already in the
      public domain and potentially very large pedigreed populations can be accessed.

PMID- 16886997
TI  - Selective transcriptional profiling for trait-based eQTL mapping.
AB  - There is currently great interest in identifying genetic loci associated with the
      expression of one or more genes by combining methods for the mapping of
      quantitative trait loci (QTL) with microarray technology. Because of the high
      cost of microarrays, it is useful to develop strategies for selecting a subset of
      individuals for expression profiling. We describe a method of selective
      transcriptional profiling that uses available information on individual
      quantitative traits and marker data to choose an optimal set of individuals for
      measurement with microarrays. We show how to analyse the resulting data to
      identify genes whose expression is associated with a QTL for a traditional trait
      or any other locus. Examples are used to illustrate the method and highlight some
      challenges associated with the analysis of selected data.

PMID- 16886998
TI  - Novel integrative genomics strategies to identify genes for complex traits.
AB  - Forward genetics is a common approach to dissecting complex traits like common
      human diseases. The ultimate aim of this approach was the identification of genes
      that are causal for disease or other phenotypes of interest. However, the forward
      genetics approach is by definition restricted to the identification of genes that
      have incurred mutations over the course of evolution or that incurred mutations
      as a result of chemical mutagenesis, and that as a result lead to disease or to
      variations in other phenotypes of interest. Genes that harbour no such mutations,
      but that play key roles in parts of the biological network that lead to disease,
      are systematically missed by this class of approaches. Recently, a class of novel
      integrative genomics approaches has been devised to elucidate the complexity of
      common human diseases by intersecting genotypic, molecular profiling, and
      clinical data in segregating populations. These novel approaches take a more
      holistic view of biological systems and leverage the vast network of gene-gene
      interactions, in combination with DNA variation data, to establish causal
      relationships among molecular profiling traits and between molecular profiling
      and disease (or other classic phenotypes). A number of novel genes for disease
      phenotypes have been identified as a result of these approaches, highlighting the
      utility of integrating orthogonal sources of data to get at the underlying causes
      of disease.

PMID- 16886999
TI  - Genetic analysis of NHLH2 and its putative role in bovine body weight control.
AB  - The control of energy balance is fundamental to adult animals and is necessary
      for weight gain/loss, reproductive capacity and general health. In mice, targeted
      deletion of the neuronal transcription factor Nhlh2 results in adult-onset
      obesity because of reduced exercise and infertility because of reduced sexual
      behaviour. Nhlh2 (NHLH2 for humans) is expressed in the hypothalamus,
      particularly in neurons that have been shown to regulate energy balance. We have
      cloned the bovine Nhlh2 gene (bNHLH2) and we have shown that bNHLH2 is also
      expressed in the hypothalamus. Phylogenetic analysis of Nhlh2 reveals that it is
      very highly conserved in humans, mice, chimps and cattle, and found in organisms
      with simpler nervous systems, including Caenorhabditis elegans and Drosophila.
      Using a cattle-human comparative map and online databases, we have evidence that
      bNHLH2 is located near a quantitative trait locus for marbling on bovine
      chromosome 3 between microsatellite markers BM723 and BMS963. Cloning of the
      bNHLH2 gene from Holstein cattle and a mixed breed individual and comparison with
      Hereford sequences shows that the gene is highly conserved among bovine breeds.

PMID- 16887000
TI  - From information to understanding: the role of model organism databases in
      comparative and functional genomics.
AB  - Data integration is key to functional and comparative genomics because
      integration allows diverse data types to be evaluated in new contexts. To achieve
      data integration in a scalable and sensible way, semantic standards are needed,
      both for naming things (standardized nomenclatures, use of key words) and also
      for knowledge representation. The Mouse Genome Informatics database and other
      model organism databases help to close the gap between information and
      understanding of biological processes because these resources enforce well
      defined nomenclature and knowledge representation standards. Model organism
      databases have a critical role to play in ensuring that diverse kinds of data,
      especially genome-scale data sets and information, remain useful to the
      biological community in the long-term. The efforts of model organism database
      groups ensure not only that organism-specific data are integrated, curated and
      accessible but also that the information is structured in such a way that
      comparison of biological knowledge across model organisms is facilitated.

PMID- 16887001
TI  - Genomic pathways database and biological data management.
AB  - In this paper, we discuss the properties of biological data and challenges it
      poses for data management, and argue that, in order to meet the data management
      requirements for 'digital biology', careful integration of the existing
      technologies and the development of new data management techniques for biological
      data are needed. Based on this premise, we present PathCase: Case Pathways
      Database System. PathCase is an integrated set of software tools for modelling,
      storing, analysing, visualizing and querying biological pathways data at
      different levels of genetic, molecular, biochemical and organismal detail. The
      novel features of the system include: (i) genomic information integrated with
      other biological data and presented starting from pathways; (ii) design for
      biologists who are possibly unfamiliar with genomics, but whose research is
      essential for annotating gene and genome sequences with biological functions;
      (iii) database design, implementation and graphical tools which enable users to
      visualize pathways data in multiple abstraction levels and to pose exploratory
      queries; (iv) a wide range of different types of queries including, 'path' and
      'neighbourhood queries' and graphical visualization of query outputs; and (v) an
      implementation that allows for web (XML)-based dissemination of query outputs
      (i.e. pathways data in BIOPAX format) to researchers in the community, giving
      them control on the use of pathways data.

PMID- 16887002
TI  - From 'omes to biology.
AB  - Technologies that have emerged from the genome project have dramatically
      increased our ability to generate data on the way in which organisms respond to
      their environments, how they execute their programmes of development and growth,
      and how these are altered in the development of disease states. However, our
      ability to analyse these large datasets has not kept pace with our ability to
      generate them and consequently new strategies must be developed to address the
      issues associated with their analysis. One approach that we have employed quite
      successfully is to look at data from microarrays (or proteomics or metabolomics
      experiments) not as independent datasets, but rather as elements of a much larger
      body of biological information across various scales that must be integrated
      with, and interpreted within, the context of such ancillary data. Here we outline
      the general approach and provide three examples from published studies of the way
      in which we have applied this strategy.

PMID- 16887004
TI  - 'Progression towards the minimum': the importance of standardizing the priming
      volume during the indirect measurement of intra-abdominal pressures.
AB  - The abdominal compartment syndrome is a state of serious organ dysfunction. The
      syndrome results from sustained intra-abdominal hypertension, which is indirectly
      identified by measuring intra-bladder pressures (IBPs) using various priming
      volumes. This technique is poorly standardized across published data. Malbrain
      and Deeren have identified the risk of falsely elevated IBPs with instillation
      priming volumes greater than 50 ml. This overestimation appears to increase with
      larger priming aliquots. As a result, erroneous IBP measurements may incorrectly
      label a patient with the abdominal compartment syndrome, and therefore subject
      them to the potential complications of surgical and/or medical decompression
      techniques. The utility and benefit of using continuous IBP monitoring is
      discussed. These data require confirmation in other patient subgroups with
      younger ages, altered body mass indices and varied diagnoses.

PMID- 16887005
TI  - Acute respiratory failure in the elderly.
AB  - With the current epidemiology of a growing advanced-age population and the
      specificities of critical illness in elderly patients, studies on this topic are
      appropriate. We need more clinical trials and evaluations of diagnostic and
      management procedures applied in the elderly, as well as studies designed to
      identify prognostic factors for inhospital mortality or mortality in the
      intensive care unit in the elderly. Studies evaluating long-term outcomes,
      including quality of life and costs, are also needed to try to define realistic
      goals for patients, families and physicians.

PMID- 16887006
TI  - Activated protein C in sepsis: down but not out, yet.

PMID- 16887003
TI  - Mouse models of breast cancer metastasis.
AB  - Metastatic spread of cancer cells is the main cause of death of breast cancer
      patients, and elucidation of the molecular mechanisms underlying this process is
      a major focus in cancer research. The identification of appropriate therapeutic
      targets and proof-of-concept experimentation involves an increasing number of
      experimental mouse models, including spontaneous and chemically induced
      carcinogenesis, tumor transplantation, and transgenic and/or knockout mice. Here
      we give a progress report on how mouse models have contributed to our
      understanding of the molecular processes underlying breast cancer metastasis and
      on how such experimentation can open new avenues to the development of innovative
      cancer therapy.

PMID- 16887008
TI  - The outcomes of severe sepsis and septic shock in the UK.

PMID- 16887007
TI  - Single nucleotide polymorphisms and breast cancer: not yet a success story.
AB  - Numerous studies have examined low penetrance susceptibility polymorphisms in
      candidate genes, with some reporting significant findings. However, for the most
      part these associations could not be replicated in subsequent studies, suggesting
      that the original observations were due to chance. The failure to identify
      meaningful common genetic variation in relation to breast cancer should give us
      pause for thought and make us reconsider our current research strategies. The
      most recent directions of pooling samples to increase statistical power and
      pursuing whole genome screens may overcome some obstacles while also creating new
      challenges. Future studies should perhaps also consider alternative designs such
      as using surrogate (preferably continuous) markers of breast cancer, focusing on
      high-risk populations, and defining pathologically distinct outcomes.

PMID- 16887009
TI  - The proximate determinants of insect size.
AB  - One of the least understood aspects of animal development--the determination of
      body size--is currently the subject of intense scrutiny. A new study employs a
      modeling approach to expose the factors that matter in the control of insect
      size.

PMID- 16887011
TI  - Measuring extravascular lung water: animals and humans are not the same.

PMID- 16887010
TI  - Biology and therapy of fibromyalgia. Genetic aspects of fibromyalgia syndrome.
AB  - Genetic and environmental factors may play a role in the etiopathology of
      fibromyalgia syndrome (FMS) and other related syndromes. There is a high
      aggregation of FMS in families of FMS patients. The mode of inheritance is
      unknown but it is most probably polygenic. There is evidence that polymorphisms
      of genes in the serotoninergic, dopaminergic and catecholaminergic systems play a
      role in the etiology of FMS. These polymorphisms are not specific for FMS and are
      associated with other functional somatic disorders and depression. Future genetic
      studies in the field of FMS and related conditions should be conducted in larger
      cohorts of patients and ethnically matched control groups.

PMID- 16887012
TI  - The outcome of patients presenting to the emergency department with severe sepsis
      or septic shock.
AB  - Although multiple studies of acute myocardial infarction, trauma, and stroke have
      been translated into improved outcomes by applying diagnosis and therapy at the
      most proximal stage of hospital presentation (before intensive care unit
      arrival), this approach to the sepsis patient has been lacking. In response to
      this, a trial comparing early goal-directed therapy (EGDT) versus standard care
      was performed using internally and externally validated criteria for early
      identification of high risk patients, established definitions, and a consensus
      derived protocol to reverse the hemodynamic perturbations of hypovolemia,
      vasoregulation, myocardial suppression and increased metabolic demands. That
      trial of EGDT resulted in significant reductions in morbidity, mortality,
      vasopressor use, and health care resource consumption. The end-points used in the
      protocol and the outcome results were subsequently externally validated,
      revealing similar or better mortality benefit. This commentary examines the
      rational and validation for the use of early markers of illness severity. Current
      evidence support the endpoints in the EGDT protocol, external validity in regards
      to outcome benefit and the universal need to improve the quality of care for
      early sepsis.

PMID- 16887013
TI  - Allowing for spontaneous breathing during high-frequency oscillation: the key for
      final success?
AB  - In the present issue of Critical Care, van Heerde and colleagues describe a new
      technical development (a flow-demand system during high-frequency oscillation)
      that may have an important impact on the future use of high-frequency ventilation
      in children and adults. Flow compensation on patient demand seems to reduce the
      imposed work of breathing, may therefore increase patient comfort, and should
      theoretically allow for maintaining spontaneous breathing while heavy sedation
      and muscular paralysis could be avoided. With further technical development of
      this concept, high-frequency oscillation can finally be added to the techniques
      of mechanical ventilatory support that maintain, rather than suppress,
      spontaneous breathing efforts. Furthermore, this concept will give high-frequency
      oscillation the chance to prove its potential role as primary therapy in patients
      with acute lung injury/acute respiratory distress syndrome, the chance to reduce
      the incidence of high-frequency oscillation failure for patient or physician
      discomfort as reported in so many clinical trials in the past, the chance to most
      probably allow successful weaning from high-frequency oscillation to extubation,
      and, ultimately, in analogy to what has been reported from the experience with
      other ventilator modes that allow for maintaining spontaneous breathing, the
      chance to decrease ventilator days in patients with acute lung injury/acute
      respiratory distress syndrome.

PMID- 16887015
TI  - Knowledge of the abortion legislation among South African women: a cross
      sectional study.
AB  - BACKGROUND: In order to ensure that legalized abortion in South Africa improves
      reproductive health, women must know that abortion is a legal option in the case
      of unwanted pregnancy. This study investigated knowledge of abortion legislation
      eight years after the introduction of legal abortion services in one province of
      South Africa. METHODS: In 2004/2005, we conducted a cross-sectional study among
      831 sexually-active women attending 26 public health clinics in one urban and one
      rural health region of the Western Cape Province. RESULTS: Thirty-two percent of
      women did not know that abortion is currently legal. Among those who knew of
      legal abortion, few had knowledge of the time restrictions involved. CONCLUSION:
      In South Africa there is an unmet need among women for information on abortion.
      Strategies should be developed to address this gap so that women are fully
      informed of their rights to a safe and legal termination of pregnancy.

PMID- 16887014
TI  - Familial, structural, and environmental correlates of MRI-defined bone marrow
      lesions: a sibpair study.
AB  - The aim of this study was to estimate the heritability and describe the
      correlates of bone marrow lesions in knee subchondral bone. A sibpair design was
      used. T2- and T1-weighted MRI scans were performed on the right knee to assess
      bone marrow lesions at lateral tibia and femora and medial tibia and femora, as
      well as chondral defects. A radiograph was taken on the same knee and scored for
      individual features of osteoarthritis (radiographic osteoarthritis; ROA) and
      alignment. Other variables measured included height, weight, knee pain, and lower
      limb muscle strength. Heritability was estimated with the program SOLAR
      (Sequential Oligogenetic Linkage Analysis Routines). A total of 115 siblings (60
      females and 55 males) from 48 families, representing 95 sib pairs, took part. The
      adjusted heritability estimates were 53 +/- 28% (mean +/- SEM; p = 0.03) and 65
      +/- 32% (p = 0.03) for severity of bone marrow lesions at lateral and medial
      compartments, respectively. The estimates were reduced by 8 to 9% after
      adjustment for chondral defects and ROA (but not alignment). The adjusted
      heritability estimate was 99% for prevalent bone marrow lesions at both lateral
      and medial compartments. Both lateral and medial bone marrow lesions were
      significantly correlated with age, chondral defects, and ROA of the knee (all p <
      0.05). Medial bone marrow lesions were also more common in males and were
      correlated with body mass index (BMI). Thus, bone marrow lesions have a
      significant genetic component. They commonly coexist with chondral defects and
      ROA but only share common genetic mechanisms to a limited degree. They are also
      more common with increasing age, male sex, and increasing BMI.

PMID- 16887016
TI  - Case-control geographic clustering for residential histories accounting for risk
      factors and covariates.
AB  - BACKGROUND: Methods for analyzing space-time variation in risk in case-control
      studies typically ignore residential mobility. We develop an approach for
      analyzing case-control data for mobile individuals and apply it to study bladder
      cancer in 11 counties in southeastern Michigan. At this time data collection is
      incomplete and no inferences should be drawn - we analyze these data to
      demonstrate the novel methods. Global, local and focused clustering of
      residential histories for 219 cases and 437 controls is quantified using time
      dependent nearest neighbor relationships. Business address histories for 268
      industries that release known or suspected bladder cancer carcinogens are
      analyzed. A logistic model accounting for smoking, gender, age, race and
      education specifies the probability of being a case, and is incorporated into the
      cluster randomization procedures. Sensitivity of clustering to definition of the
      proximity metric is assessed for 1 to 75 k nearest neighbors. RESULTS: Global
      clustering is partly explained by the covariates but remains statistically
      significant at 12 of the 14 levels of k considered. After accounting for the
      covariates 26 Local clusters are found in Lapeer, Ingham, Oakland and Jackson
      counties, with the clusters in Ingham and Oakland counties appearing in 1950 and
      persisting to the present. Statistically significant focused clusters are found
      about the business address histories of 22 industries located in Oakland (19
      clusters), Ingham (2) and Jackson (1) counties. Clusters in central and
      southeastern Oakland County appear in the 1930's and persist to the present day.
      CONCLUSION: These methods provide a systematic approach for evaluating a series
      of increasingly realistic alternative hypotheses regarding the sources of excess
      risk. So long as selection of cases and controls is population-based and not
      geographically biased, these tools can provide insights into geographic risk
      factors that were not specifically assessed in the case-control study design.

PMID- 16887017
TI  - Comparative proteomic analysis of metabolically labelled proteins from Plasmodium
      falciparum isolates with different adhesion properties.
AB  - The virulence of Plasmodium falciparum relates in part to the cytoadhesion
      characteristics of parasitized erythrocytes but the molecular basis of the
      different qualitative and quantitative binding phenotypes is incompletely
      understood. This paucity of information is due partly to the difficulty in
      working with membrane proteins, the variant nature of these surface antigens and
      their relatively low abundance. To address this two-dimensional (2D) protein
      profiles of closely related, but phenotypically different laboratory strains of
      P. falciparum have been characterized using proteomic approaches. Since the
      mature erythrocyte has no nucleus and no protein synthesis capability, metabolic
      labelling of proteins was used to selectively identify parasite proteins and
      increase detection sensitivity.A small number of changes (less than 10) were
      observed between four different P. falciparum laboratory strains with distinctive
      cytoadherence properties using metabolic labelling, with more parasite protein
      changes found in trophozoite iRBCs than ring stage. The combination of metabolic
      labelling and autoradiography can therefore be used to identify parasite protein
      differences, including quantitative ones, and in some cases to obtain protein
      identifications by mass spectrometry. The results support the suggestion that the
      membrane protein profile may be related to cytoadherent properties of the iRBCs.
      Most changes between parasite variants were differences in iso-electric point
      indicating differential protein modification rather than the presence or absence
      of a specific peptide.

PMID- 16887018
TI  - High-risk surgical stage 1 endometrial cancer: analysis of treatment outcome.
AB  - PURPOSE: To report the relapse and survival rates associated to treatment for
      patients with stage IC, grade 2 or grade 3 and IB grade 3 diseases considered
      high risk patients group for relapse. MATERIALS AND METHODS: From January 1993 to
      December 2003, 106 patients with endometrial cancer stage I were managed
      surgically in our institution. Based on data from the medical records, 106
      patients with epithelial endometrial cancer met the following inclusion criteria:
      stage IC grade 2 or 3 and IB grade 3 with or without lymphovascular invasion.
      Staging was defined according to the FIGO surgical staging system. Postoperative
      adjuvant radiotherapy consisted of external beam pelvic radiation, vaginal
      brachytherapy alone or both. The median age was 65 years (range, 32-83 years),
      lymph node dissection was performed in 45 patients (42.5%) and 14 patients
      (13.2%) received vaginal brachytherapy only, and 92 (86.8%) received combined
      vaginal brachytherapy and external beam radiotherapy. The median dose of external
      beam radiotherapy administered to the pelvis was 4500 cGy (range 4000-5040). The
      median dose to vaginal surface was 2400 cGy (range 2000-3000). Predominant
      pathological stage and histological grade were IC (73.6%) and grade 3 (51.9%).
      The lymphovascular invasion was present in 33 patients (31.1%) and pathological
      stage IC grade 2 was most common (48. 1%) combination of risk factors in this
      group. RESULTS: With a follow up median of 58.3 months (range 12.8-154), five
      year overall survival and event free survival were 78.5% and 72.4%, respectively.
      Locoregional control in five year was 92.4%. Prognostic factors related with
      survival in univariate analyses were: lymphadenectomy (p = 0.045), lymphovascular
      invasion (p = 0.047) and initial failure site (p < 0.0001). In multivariate
      analyses the initial failure in distant sites (p < 0.0001) was the only factor
      associated with poor survival. Acute and chronic gastrointestinal and
      genitourinary toxicity grades 3 were not observed. CONCLUSION: In conclusion, our
      results showed that the stage IC, grade 2, 3 and IB grade 3 endometrial cancer
      was associated with significantly increased risk of distant relapse and
      endometrial carcinoma-related death independently of salvage treatment modality.

PMID- 16887019
TI  - Establishing a gold standard for manual cough counting: video versus digital
      audio recordings.
AB  - BACKGROUND: Manual cough counting is time-consuming and laborious; however it is
      the standard to which automated cough monitoring devices must be compared. We
      have compared manual cough counting from video recordings with manual cough
      counting from digital audio recordings. METHODS: We studied 8 patients with
      chronic cough, overnight in laboratory conditions (diagnoses were 5 asthma, 1
      rhinitis, 1 gastro-oesophageal reflux disease and 1 idiopathic cough). Coughs
      were recorded simultaneously using a video camera with infrared lighting and
      digital sound recording. The numbers of coughs in each 8 hour recording were
      counted manually, by a trained observer, in real time from the video recordings
      and using audio-editing software from the digital sound recordings. RESULTS: The
      median cough frequency was 17.8 (IQR 5.9-28.7) cough sounds per hour in the video
      recordings and 17.7 (6.0-29.4) coughs per hour in the digital sound recordings.
      There was excellent agreement between the video and digital audio cough rates;
      mean difference of -0.3 coughs per hour (SD +/- 0.6), 95% limits of agreement 
      1.5 to +0.9 coughs per hour. Video recordings had poorer sound quality even in
      controlled conditions and can only be analysed in real time (8 hours per
      recording). Digital sound recordings required 2-4 hours of analysis per
      recording. CONCLUSION: Manual counting of cough sounds from digital audio
      recordings has excellent agreement with simultaneous video recordings in
      laboratory conditions. We suggest that ambulatory digital audio recording is
      therefore ideal for validating future cough monitoring devices, as this as this
      can be performed in the patients own environment.

PMID- 16887020
TI  - Kinetic modeling of tricarboxylic acid cycle and glyoxylate bypass in
      Mycobacterium tuberculosis, and its application to assessment of drug targets.
AB  - BACKGROUND: Targeting persistent tubercule bacilli has become an important
      challenge in the development of anti-tuberculous drugs. As the glyoxylate bypass
      is essential for persistent bacilli, interference with it holds the potential for
      designing new antibacterial drugs. We have developed kinetic models of the
      tricarboxylic acid cycle and glyoxylate bypass in Escherichia coli and
      Mycobacterium tuberculosis, and studied the effects of inhibition of various
      enzymes in the M. tuberculosis model. RESULTS: We used E. coli to validate the
      pathway-modeling protocol and showed that changes in metabolic flux can be
      estimated from gene expression data. The M. tuberculosis model reproduced the
      observation that deletion of one of the two isocitrate lyase genes has little
      effect on bacterial growth in macrophages, but deletion of both genes leads to
      the elimination of the bacilli from the lungs. It also substantiated the
      inhibition of isocitrate lyases by 3-nitropropionate. On the basis of our
      simulation studies, we propose that: (i) fractional inactivation of both
      isocitrate dehydrogenase 1 and isocitrate dehydrogenase 2 is required for a flux
      through the glyoxylate bypass in persistent mycobacteria; and (ii) increasing the
      amount of active isocitrate dehydrogenases can stop the flux through the
      glyoxylate bypass, so the kinase that inactivates isocitrate dehydrogenase 1
      and/or the proposed inactivator of isocitrate dehydrogenase 2 is a potential
      target for drugs against persistent mycobacteria. In addition, competitive
      inhibition of isocitrate lyases along with a reduction in the inactivation of
      isocitrate dehydrogenases appears to be a feasible strategy for targeting
      persistent mycobacteria. CONCLUSION: We used kinetic modeling of biochemical
      pathways to assess various potential anti-tuberculous drug targets that interfere
      with the glyoxylate bypass flux, and indicated the type of inhibition needed to
      eliminate the pathogen. The advantage of such an approach to the assessment of
      drug targets is that it facilitates the study of systemic effect(s) of the
      modulation of the target enzyme(s) in the cellular environment.

PMID- 16887021
TI  - Radiosensitization of colorectal carcinoma cell lines by histone deacetylase
      inhibition.
AB  - BACKGROUND: The tumor response to preoperative radiotherapy of locally advanced
      rectal cancer varies greatly, warranting the use of experimental models to assay
      the efficacy of molecular targeting agents in rectal cancer radiosensitization.
      Histone deacetylase (HDAC) inhibitors, agents that cause hyperacetylation of
      histone proteins and thereby remodeling of chromatin structure, may override cell
      cycle checkpoint responses to DNA damage and amplify radiation-induced tumor cell
      death. METHODS: Human colorectal carcinoma cell lines were exposed to ionizing
      radiation and HDAC inhibitors, and cell cycle profiles and regulatory factors, as
      well as clonogenicity, were analyzed. RESULTS: In addition to G(2)/M phase arrest
      following irradiation, the cell lines displayed cell cycle responses typical for
      either intact or defective p53 function (the presence or absence, respectively,
      of radiation-induced expression of the cell cycle inhibitor p21 and subsequent
      accumulation of G(1) phase cells). In contrast, histone acetylation was
      associated with complete depletion of the G1 population of cells with functional
      p53 but accumulation of both G(1) and G(2)/M populations of cells with defective
      p53. The cellular phenotypes upon HDAC inhibition were consistent with the
      observed repression of Polo-like kinase-1, a regulatory G(2)/M phase kinase.
      Following pre-treatment with HDAC inhibitors currently undergoing clinical
      investigation, the inhibitory effect of ionizing radiation on clonogenicity was
      significantly amplified. CONCLUSION: In these experimental models, HDAC
      inhibition sensitized the tumor cells to ionizing radiation, which is in
      accordance with the concept of increased probability of tumor cell death when
      chromatin structure is modified.

PMID- 16887022
TI  - Service utilization in community health centers in China: a comparison analysis
      with local hospitals.
AB  - BACKGROUND: Being an important part of China's Urban Health Care Reform System,
      Community Health Centers (CHCs) have been established throughout the entire
      country and are presently undergoing substantial reconstruction. However, the
      services being delivered by the CHCs are far from reaching their performance
      targets. In order to assess the role of the CHCs, we examined their performance
      in six cities located in regions of South-East China. The purpose of this
      investigation was to identify the utilization and the efficiency of community
      health resources that are able to provide basic medical and public health
      services. METHODS: The study was approved by Peking University Health Science
      Center Institutional Reviewing Board (NO: IRB00001052-T1). Data were collected
      from all the local health bureaux and processed using SPSS software. Methods of
      analysis mainly included: descriptive analysis, paired T-test and one-way ANOVA.
      RESULTS: The six main functions of the CHCs were not fully exploited and the
      surveys that were collected on their efficiency and utilization of resources
      indicate that they have a low level of performance and lack the trust of local
      communities. Furthermore, the CHCs seriously lack funding support and operate
      under difficult circumstances, and residents have less positive attitudes towards
      them. CONCLUSION: The community health service must be adjusted according to the
      requirements of urban medical and health reform, taking into account communities'
      health needs. More research is required on the living standards and health needs
      of residents living within the CHC's range, taking into consideration the users'
      needs in expanding the newly implemented service, and at the same time revising
      the old service system so as to make the development of CHCs realistic and
      capable of providing a better service to patients. Several suggestions are put
      forward for an attainable scheme for developing a community health service.

PMID- 16887023
TI  - The IMAGE project: methodological issues for the molecular genetic analysis of
      ADHD.
AB  - The genetic mechanisms involved in attention deficit hyperactivity disorder
      (ADHD) are being studied with considerable success by several centres worldwide.
      These studies confirm prior hypotheses about the role of genetic variation within
      genes involved in the regulation of dopamine, norepinephrine and serotonin
      neurotransmission in susceptibility to ADHD. Despite the importance of these
      findings, uncertainties remain due to the very small effects sizes that are
      observed. We discuss possible reasons for why the true strength of the
      associations may have been underestimated in research to date, considering the
      effects of linkage disequilibrium, allelic heterogeneity, population differences
      and gene by environment interactions. With the identification of genes associated
      with ADHD, the goal of ADHD genetics is now shifting from gene discovery towards
      gene functionality--the study of intermediate phenotypes ('endophenotypes'). We
      discuss methodological issues relating to quantitative genetic data from twin and
      family studies on candidate endophenotypes and how such data can inform attempts
      to link molecular genetic data to cognitive, affective and motivational processes
      in ADHD. The International Multi-centre ADHD Gene (IMAGE) project exemplifies
      current collaborative research efforts on the genetics of ADHD. This European
      multi-site project is well placed to take advantage of the resources that are
      emerging following the sequencing of the human genome and the development of
      international resources for whole genome association analysis. As a result of
      IMAGE and other molecular genetic investigations of ADHD, we envisage a rapid
      increase in the number of identified genetic variants and the promise of
      identifying novel gene systems that we are not currently investigating, opening
      further doors in the study of gene functionality.

PMID- 16887024
TI  - Single and multiple dose pharmacokinetics of maritime pine bark extract
      (pycnogenol) after oral administration to healthy volunteers.
AB  - BACKGROUND: Since plant extracts are increasingly used as phytotherapeutics or
      dietary supplements information on bioavailability, bioefficacy and safety are
      warranted. We elucidated the plasma kinetics of genuine extract components and
      metabolites after single and multiple ingestion of the standardized maritime pine
      bark extract Pycnogenol (USP quality) by human volunteers. METHODS: Eleven
      volunteers received a single dose of 300 mg pine bark extract, five volunteers
      ingested 200 mg daily for five days to reach steady state concentrations. Plasma
      samples were obtained before and at defined time points after intake of the
      extract. Samples were analyzed by HPLC with ion-pair reagents and simultaneous UV
      and electrochemical detection. RESULTS: We quantified total plasma concentrations
      of catechin, caffeic acid, ferulic acid, taxifolin and the metabolite M1 (delta
      (3,4-dihydroxy-phenyl)-gamma-valerolactone). Additionally, we describe plasma
      time courses and steady state appearance of ten so far unknown compounds, U1 to
      U10. After single ingestion, compounds derived from the extract were rapidly
      absorbed and the majority of them were detectable over whole experimental period
      of 14 h. The analysis of steady state plasma samples revealed significant phase
      II metabolism. CONCLUSION: We present the first systematic pharmacokinetic
      analysis of compounds derived from maritime pine bark extract. Beyond the known
      constituents and metabolites we uncovered the plasma time courses of ten unknown
      compounds. In concert with our previous detection of anti-inflammatory
      bioefficacy of these plasma samples ex vivo we suggest that constituents and
      metabolites of Pycnogenol bear potential for disclosure of novel active
      principles.

PMID- 16887025
TI  - Advertising and disclosure of funding on patient organisation websites: a cross
      sectional survey.
AB  - BACKGROUND: Patient organisations may be exposed to conflicts of interest and
      undue influence through pharmaceutical industry (Pharma) donations. We examined
      advertising and disclosure of financial support by pharmaceutical companies on
      the websites of major patient organisations. METHOD: Sixty-nine national and
      international patient organisations covering 10 disease states were identified
      using a defined Google search strategy. These were assessed for indicators of
      transparency, advertising, and disclosure of Pharma funding using an abstraction
      tool and inspection of annual reports. Data were analysed by simple tally, with
      medians calculated for financial data. RESULTS: Patient organisations websites
      were clear about their identity, target audience and intention but only a third
      were clear on how they derived their funds. Only 4/69 websites stated advertising
      and conflict of interest policies. Advertising was generally absent. 54% of sites
      included an annual report, but financial reporting and disclosure of donors
      varied substantially. Corporate donations were itemised in only 7/37 reports and
      none gave enough information to show the proportion of funding from Pharma. 45%
      of organisations declared Pharma funding on their website but the annual reports
      named more Pharma donors than did the websites (median 6 vs. 1). One third of
      websites showed one or more company logos and/or had links to Pharma websites.
      Pharma companies' introductions were present on 10% of websites, some of them
      mentioning specific products. Two patient organisations had obvious close ties to
      Pharma. CONCLUSION: Patient organisation websites do not provide enough
      information for visitors to assess whether a conflict of interest with Pharma
      exists. While advertising of products is generally absent, display of logos and
      corporate advertisements is relatively common. Display of clear editorial and
      advertising policies and disclosure of the nature and degree of corporate
      donations is needed on patient organisations' websites. An ethical code to guide
      patient organisations and their staff members on how to collaborate with Pharma
      is also necessary, if patient organisations are to remain independent and truly
      represent the interests and views of patients. As many organizations rely on
      Pharma donations, self-regulation may not suffice and independent oversight
      bodies should take the lead in requiring this.

PMID- 16887026
TI  - Walker-Warburg syndrome.
AB  - Walker-Warburg Syndrome (WWS) is a rare form of autosomal recessive congenital
      muscular dystrophy associated with brain and eye abnormalities. WWS has a
      worldwide distribution. The overall incidence is unknown but a survey in North
      eastern Italy has reported an incidence rate of 1.2 per 100,000 live births. It
      is the most severe form of congenital muscular dystrophy with most children dying
      before the age of three years. WWS presents at birth with generalized hypotonia,
      muscle weakness, developmental delay with mental retardation and occasional
      seizures. It is associated with type II cobblestone lissencephaly, hydrocephalus,
      cerebellar malformations, eye abnormalities and congenital muscular dystrophy
      characterized by hypoglycosylation of alpha-dystroglycan. Several genes have been
      implicated in the etiology of WWS, and others are as yet unknown. Several
      mutations were found in the Protein O-Mannosyltransferase 1 and 2 (POMT1 and
      POMT2) genes, and one mutation was found in each of the fukutin and fukutin
      related protein (FKRP) genes. Laboratory investigations usually show elevated
      creatine kinase, myopathic/dystrophic muscle pathology and altered alpha
      dystroglycan. Antenatal diagnosis is possible in families with known mutations.
      Prenatal ultrasound may be helpful for diagnosis in families where the molecular
      defect is unknown. No specific treatment is available. Management is only
      supportive and preventive.

PMID- 16887027
TI  - Flock-level risk factors for scrapie in Great Britain: analysis of a 2002
      anonymous postal survey.
AB  - BACKGROUND: In November 2002, an anonymous postal survey of sheep farmers in
      Great Britain (GB) was conducted to identify factors associated with the flock
      level occurrence of scrapie. This survey was undertaken to update an earlier
      postal survey in 1998, and was the first occasion in which a large-scale postal
      survey had been repeated. RESULTS: The results of the 2002 survey indicated that
      scrapie was more likely to occur in certain geographic regions; in purebred
      compared to commercial flocks; in larger flocks; in flocks which lambed in group
      pens compared to those which lambed in individual pens; in flocks which always
      lambed in the same location compared to those which did not; and in farms which
      kept certain breeds of sheep. In addition to these factors, the likelihood of the
      disease occurring in homebred animals was higher in flocks which bred a greater
      proportion of replacement animals or which bought-in lambs. Finally, within-flock
      transmission following exposure was more likely to occur in hill flocks compared
      to other farm types; in flocks which bred a greater proportion of replacement
      animals; and in farms which kept a certain crossbreed of ewe. CONCLUSION: The
      risk factors identified from the 1998 and 2002 anonymous postal surveys in Great
      Britain were similar. However, differences between the surveys were identified in
      the influence of region and of purchasing behaviour on the risk of scrapie. These
      differences are most likely a consequence of changes in farmer awareness and the
      impact of the 2001 foot-and-mouth disease epidemic, respectively.

PMID- 16887028
TI  - Review conclusions by Ernst and Canter regarding spinal manipulation refuted.
AB  - In the April 2006 issue of the Journal of Royal Society of Medicine, Ernst and
      Canter authored a review of the most recent systematic reviews on the
      effectiveness of spinal manipulation for any condition. The authors concluded
      that, except for back pain, spinal manipulation is not an effective intervention
      for any condition and, because of potential side effects, cannot be recommended
      for use at all in clinical practice. Based on a critical appraisal of their
      review, the authors of this commentary seriously challenge the conclusions by
      Ernst and Canter, who did not adhere to standard systematic review methodology,
      thus threatening the validity of their conclusions. There was no systematic
      assessment of the literature pertaining to the hazards of manipulation, including
      comparison to other therapies. Hence, their claim that the risks of manipulation
      outweigh the benefits, and thus spinal manipulation cannot be recommended as
      treatment for any condition, was not supported by the data analyzed. Their
      conclusions are misleading and not based on evidence that allow discrediting of a
      large body of professionals using spinal manipulation.

PMID- 16887029
TI  - Addressing the health workforce crisis: towards a common approach.
AB  - The challenges in the health workforce are well known and clearly documented.
      What is not so clearly understood is how to address these issues in a
      comprehensive and integrated manner that will lead to solutions. This editorial
      presents--and invites comments on--a technical framework intended to raise
      awareness among donors and multisector organizations outside ministries of health
      and to guide planning and strategy development at the country level.

PMID- 16887030
TI  - Double blind randomized placebo-controlled trial on the effects of testosterone
      supplementation in elderly men with moderate to low testosterone levels: design
      and baseline characteristics [ISRCTN23688581].
AB  - In ageing men testosterone levels decline, while cognitive function, muscle and
      bone mass, sexual hair growth, libido and sexual activity decline and the risk of
      cardiovascular diseases increase. We set up a double-blind, randomized placebo
      controlled trial to investigate the effects of testosterone supplementation on
      functional mobility, quality of life, body composition, cognitive function,
      vascular function and risk factors, and bone mineral density in older hypogonadal
      men. We recruited 237 men with serum testosterone levels below 13.7 nmol/L and
      ages 60-80 years. They were randomized to either four capsules of 40 mg
      testosterone undecanoate (TU) or placebo daily for 26 weeks. Primary endpoints
      are functional mobility and quality of life. Secondary endpoints are body
      composition, cognitive function, aortic stiffness and cardiovascular risk factors
      and bone mineral density. Effects on prostate, liver and hematological parameters
      will be studied with respect to safety. Measure of effect will be the difference
      in change from baseline visit to final visit between TU and placebo. We will
      study whether the effect of TU differs across subgroups of baseline waist girth
      (< 100 cm vs. > or = 100 cm; testosterone level (< 12 versus > or = 12 nmol/L),
      age (< median versus > or = median), and level of outcome under study (< median
      versus > or = median). At baseline, mean age, BMI and testosterone levels were 67
      years, 27 kg/m2 and 10.72 nmol/L, respectively.

PMID- 16887031
TI  - Dosimetric comparison of helical tomotherapy and Gamma Knife stereotactic
      radiosurgery for single brain metastasis.
AB  - BACKGROUND: Helical Tomotherapy (HT) integrates linear accelerator and
      computerized tomography (CT) technology to deliver IMRT. Targets are localized
      (i.e. outlined as gross tumor volume [GTV] and planning target volume [PTV]) on
      the planning kVCT study while daily MVCT is used for correction of patient's set
      up and assessment of inter-fraction anatomy changes. Based on dosimetric
      comparisons, this study aims to find dosimetric equivalency between single
      fraction HT and Gamma Knife stereotactic radiosurgery (GKSRS) for the treatment
      of single brain metastasis. METHODS: The targeting MRI data set from the GKSRS
      were used for tomotherapy planning. Five patients with single brain metastasis
      treated with GKSRS were re-planned in the HT planning station using the same
      prescribed doses. There was no expansion of the GTV to create the PTV. Sub
      volumes were created within the PTV and prescribed to the maximum dose seen in
      the GKSRS plans to imitate the hot spot normally seen in GKSRS. The PTV objective
      was set as a region at risk in HT planning using the same prescribed dose to the
      PTV periphery as seen in the corresponding GKSRS plan. The tumor volumes ranged
      from 437-1840 mm(3). RESULTS: Conformality indices are inconsistent between HT
      and GKSRS. HT generally shows larger lower isodose line volumes, has longer
      treatment time than GKSRS and can treat a much larger lesion than GKSRS. Both HT
      and GKSRS single fraction dose-volume toxicity may be prohibitive in treating
      single or multiple lesions depending on the number and the sizes of the lesions.
      CONCLUSION: Based on the trend for larger lower dose volumes and more constricted
      higher dose volumes in HT as compared to GKSRS, dosimetric equivalency was not
      reached between HT and GKSRS.

PMID- 16887032
TI  - Dexamethasone diminishes the pro-inflammatory and cytotoxic effects of amyloid
      beta-protein in cerebrovascular smooth muscle cells.
AB  - BACKGROUND: Cerebrovascular deposition of fibrillar amyloid beta-protein (Abeta),
      a condition known as cerebral amyloid angiopathy (CAA), is a prominent
      pathological feature of Alzheimer's disease (AD) and related disorders.
      Accumulation of cerebral vascular fibrillar Abeta is implicated in promoting
      local neuroinflammation, causes marked degeneration of smooth muscle cells, and
      can lead to loss of vessel wall integrity with hemorrhage. However, the
      relationship between cerebral vascular fibrillar Abeta-induced inflammatory
      responses and localized cytotoxicity in the vessel wall remains unclear.Steroidal
      based anti-inflammatory agents, such as dexamethasone, have been reported to
      reduce neuroinflammation and hemorrhage associated with CAA. Nevertheless, the
      basis for the beneficial effects of steroidal anti-inflammatory drug treatment
      with respect to local inflammation and hemorrhage in CAA is unknown. The cultured
      human cerebrovascular smooth muscle (HCSM) cell system is a useful in vitro model
      to study the pathogenic effects of Abeta in CAA. To examine the possibility that
      dexamethasone may influence CAA-induced cellular pathology, we investigated the
      effect of this anti-inflammatory agent on inflammatory and cytotoxic responses to
      Abeta by HCSM cells. METHODS: Primary cultures of HCSM cells were treated with or
      without pathogenic Abeta in the presence or absence of the steroidal anti
      inflammatory agent dexamethasone or the non-steroidal anti-inflammatory drugs
      indomethacin or ibuprofen. Cell viability was measured using a fluorescent live
      cell/dead cell assay. Quantitative immunoblotting was performed to determine the
      amount of cell surface Abeta and amyloid beta-protein precursor (AbetaPP)
      accumulation and loss of vascular smooth cell alpha actin. To assess the extent
      of inflammation secreted interleukin-6 (IL-6) levels were measured by ELISA and
      active matrix metalloproteinase-2 (MMP-2) levels were evaluated by gelatin
      zymography. RESULTS: Pathogenic Abeta-induced HCSM cell death was markedly
      reduced by dexamethasone but was unaffected by ibuprofen or indomethacin.
      Dexamethasone had no effect on the initial pathogenic effects of Abeta including
      HCSM cell surface binding, cell surface fibril-like assembly, and accumulation of
      cell surface AbetaPP. However, later stage pathological consequences of Abeta
      treatment associated with inflammation and cell degeneration including increased
      levels of IL-6, activation of MMP-2, and loss of HCSM alpha actin were
      significantly diminished by dexamethasone but not by indomethacin or ibuprofen.
      CONCLUSION: Our results suggest that although dexamethasone has no appreciable
      consequence on HCSM cell surface fibrillar Abeta accumulation it effectively
      reduces the subsequent pathologic responses including elevated levels of IL-6,
      MMP-2 activation, and depletion of HCSM alpha actin. Dexamethasone, unlike
      indomethacin or ibuprofen, may diminish these pathological processes that likely
      contribute to inflammation and loss of vessel wall integrity leading to
      hemorrhage in CAA.

PMID- 16887034
TI  - Generation of a large scale repertoire of Expressed Sequence Tags (ESTs) from
      normalised rainbow trout cDNA libraries.
AB  - BACKGROUND: Within the framework of a genomics project on livestock species
      (AGENAE), we initiated a high-throughput DNA sequencing program of Expressed
      Sequence Tags (ESTs) in rainbow trout, Oncorhynchus mykiss. RESULTS: We
      constructed three cDNA libraries including one highly complex pooled-tissue
      library. These libraries were normalized and subtracted to reduce clone
      redundancy. ESTs sequences were produced, and 96,472 ESTs corresponding to high
      quality sequence reads were released on the international database, currently
      representing 42.5% of the overall sequence knowledge in this species. All these
      EST sequences and other publicly available ESTs in rainbow trout have been
      included on a publicly available Website (SIGENAE) and have been clustered into a
      total of 52,930 clusters of putative transcripts groups, including 24,616
      singletons. 57.1% of these 52,930 clusters are represented by at least one Agenae
      EST and 14,343 clusters (27.1%) are only composed by Agenae ESTs. Sequence
      analysis also reveals that normalization and especially subtraction were
      effective in decreasing redundancy, and that the pooled-tissue library was
      representative of the initial tissue complexity. CONCLUSION: Due to present work
      on the construction of rainbow trout normalized cDNA libraries and their
      extensive sequencing, along with other large scale sequencing programs, rainbow
      trout is now one of the major fish models in term of EST sequences available in a
      public database, just after Zebrafish, Danio rerio. This information is now used
      for the selection of a non redundant set of clones for producing DNA micro-arrays
      in order to examine global gene expression.

PMID- 16887033
TI  - Polymorphisms in the glucocerebrosidase gene and pseudogene urge caution in
      clinical analysis of Gaucher disease allele c.1448T>C (L444P).
AB  - BACKGROUND: Gaucher disease is a potentially severe lysosomal storage disorder
      caused by mutations in the human glucocerebrosidase gene (GBA). We have developed
      a multiplexed genetic assay for eight diseases prevalent in the Ashkenazi
      population: Tay-Sachs, Gaucher type I, Niemann-Pick types A and B, mucolipidosis
      type IV, familial dysautonomia, Canavan, Bloom syndrome, and Fanconi anemia type
      C. This assay includes an allelic determination for GBA allele c.1448T>C (L444P).
      The goal of this study was to clinically evaluate this assay. METHODS:
      Biotinylated, multiplex PCR products were directly hybridized to capture probes
      immobilized on fluorescently addressed microspheres. After incubation with
      streptavidin-conjugated fluorophore, the reactions were analyzed by Luminex
      IS100. Clinical evaluations were conducted using de-identified patient DNA
      samples. RESULTS: We evaluated a multiplexed suspension array assay that includes
      wild-type and mutant genetic determinations for Gaucher disease allele c.1448T>C.
      Two percent of samples reported to be wild-type by conventional methods were
      observed to be c.1448T>C heterozygous using our assay. Sequence analysis
      suggested that this phenomenon was due to co-amplification of the functional gene
      and a paralogous pseudogene (PsiGBA) due to a polymorphism in the primer-binding
      site of the latter. Primers for the amplification of this allele were then
      repositioned to span an upstream deletion in the pseudogene, yielding a much
      longer amplicon. Although it is widely reported that long amplicons negatively
      impact amplification or detection efficiency in recently adopted multiplex
      techniques, this assay design functioned properly and resolved the occurrence of
      false heterozygosity. CONCLUSION: Although previously available sequence
      information suggested GBA gene/pseudogene discrimination capabilities with a
      short amplified product, we identified common single-nucleotide polymorphisms in
      the pseudogene that required amplification of a larger region for effective
      discrimination.

PMID- 16887035
TI  - Giant pulmonary hamartoma.
AB  - Pulmonary hamartomas are usually an incidental finding and range in size from 1
      cm to 8 cm in diameter in various series. We report a case of a massive pulmonary
      hamartoma (size 25.5 x 17.5 x 6.5 cm and weighing 1134 g) in a 61 year old male
      who presented with a short history of breathlessness. The tumour was arising from
      the medial border of the right lung and occupying most of the right chest
      extending in to the anterior mediastinum. The tumour was compressing the right
      lung and there was no evidence of infiltration into the surrounding structures.
      It was successfully treated by surgical resection and final histology was
      pulmonary hamartoma with predominantly adipose and leiomyomatous differentiation.

PMID- 16887036
TI  - Potassium channel gene mutations rarely cause atrial fibrillation.
AB  - BACKGROUND: Mutations in several potassium channel subunits have been associated
      with rare forms of atrial fibrillation. In order to explore the role of potassium
      channels in inherited typical forms of the arrhythmia, we have screened a cohort
      of patients from a referral clinic for mutations in the channel subunit genes
      implicated in the arrhythmia. We sought to determine if mutations in KCNJ2 and
      KCNE1-5 are a common cause of atrial fibrillation. METHODS: Serial patients with
      lone atrial fibrillation or atrial fibrillation with hypertension were enrolled
      between June 1, 2001 and January 6, 2005. Each patient underwent a standardized
      interview and physical examination. An electrocardiogram, echocardiogram and
      blood sample for genetic analysis were also obtained. Patients with a family
      history of AF were screened for mutations in KCNJ2 and KCNE1-5 using automated
      sequencing. RESULTS: 96 patients with familial atrial fibrillation were enrolled.
      Eighty-three patients had lone atrial fibrillation and 13 had atrial fibrillation
      and hypertension. Patients had a mean age of 56 years at enrollment and 46 years
      at onset of atrial fibrillation. Eighty-one percent of patients had paroxysmal
      atrial fibrillation at enrollment. Unlike patients with an activating mutation in
      KCNQ1, the patients had a normal QTc interval with a mean of 412 +/- 42 ms.
      Echocardiography revealed a normal mean ejection fraction of 62.0 +/- 7.2 % and
      mean left atrial dimension of 39.9 +/- 7.0 mm. A number of common polymorphisms
      in KCNJ2 and KCNE1-5 were identified, but no mutations were detected. CONCLUSION:
      Mutations in KCNJ2 and KCNE1-5 rarely cause typical atrial fibrillation in a
      referral clinic population.

PMID- 16887037
TI  - Insights from a national survey into why substance abuse treatment units add
      prevention and outreach services.
AB  - BACKGROUND: Previous studies have found that even limited prevention-related
      interventions can affect health behaviors such as substance use and risky sex.
      Substance abuse treatment providers are ideal candidates to provide these
      services, but typically have little or no financial incentive to do so. The
      purpose of this study was therefore to explore why some substance abuse treatment
      units have added new prevention and outreach services. Based on an ecological
      framework of organizational strategy, three categories of predictors were tested:
      (1) environmental, (2) unit-level, and (3) unit leadership. RESULTS: A lagged
      cross-sectional logistic model of 450 outpatient substance abuse treatment units
      revealed that local per capita income, mental health center affiliation, and
      clinical supervisors' graduate degrees were positively associated with likelihood
      of adding prevention-related education and outreach services. Managed care
      contracts and methadone treatment were negatively associated with addition of
      these services. No hospital-affiliated agencies added prevention and outreach
      services during the study period. CONCLUSION: Findings supported the study's
      ecological perspective on organizational strategy, with factors at environmental,
      unit, and unit leadership levels associated with additions of prevention and
      outreach services. Among the significant predictors, ties to managed care payers
      and unit leadership graduate education emerge as potential leverage points for
      public policy. In the current sample, units with managed care contracts were less
      likely to add prevention and outreach services. This is not surprising, given
      managed care's emphasis on cost control. However, the association with this
      payment source suggests that public managed care programs might affects
      prevention and outreach differently through revised incentives. Specifically,
      government payers could explicitly compensate substance abuse treatment units in
      managed care contracts for prevention and outreach. The effects of supervisor
      graduate education on likelihood of adding new prevention and outreach programs
      suggests that leaders' education can affect organizational strategy. Foundation
      and government officials may encourage prevention and outreach by funding
      curricular enhancements to graduate degree programs demonstrating the importance
      of public goods. Overall, these findings suggest that both money and professional
      education affect substance abuse treatment unit additions of prevention and
      outreach services, as well as other factors less amenable to policy intervention.

PMID- 16887038
TI  - An inventory of mucin genes in the chicken genome shows that the mucin domain of
      Muc13 is encoded by multiple exons and that ovomucin is part of a locus of
      related gel-forming mucins.
AB  - BACKGROUND: Mucins are large glycoproteins that cover epithelial surfaces of the
      body. All mucins contain at least one PTS domain, a region rich in proline,
      threonine and serine. Mucins are also characterized by von Willebrand D (VWD)
      domains or SEA domains. We have developed computational methods to identify mucin
      genes and proteins based on these properties of the proteins. Using such methods
      we are able to characterize different organisms where genome sequence is
      available with respect to their mucin repertoire. RESULTS: We have here made a
      comprehensive analysis of potential mucins encoded by the chicken (Gallus gallus)
      genome. Three transmembrane mucins (Muc4, Muc13, and Muc16) and four gel-forming
      mucins (Muc6, Muc2, Muc5ac, and Muc5b) were identified. The gel-forming mucins
      are encoded within a locus similar to the corresponding human mucins. However,
      the chicken has an additional gene inserted between Muc2 and Muc5ac that encodes
      the the alpha-subunit of ovomucin, a protein similar to Muc2, but it is lacking a
      PTS domain. We also show that the beta-subunit of ovomucin is the orthologue of
      human MUC6. The transmembrane Muc13 gene is in chicken as well as in mammals
      adjacent to the HEG (heart of glass) gene. HEG has PTS, EGF and transmembrane
      domains like Muc13, suggesting that these two proteins are evolutionary related.
      Unlike previously known mucins, the PTS domain of Muc13 is encoded by multiple
      exons, where each exon encodes a repeat unit of the PTS domain. CONCLUSION: We
      report new mucin homologues in chicken and this information will aid in
      understanding the evolution of mucins in vertebrates. The fact that ovomucin, a
      protein not found in mammals, was located in the same locus as other gel-forming
      mucins provides strong support that these proteins are evolutionary related.
      Furthermore, a relationship of HEG and the transmembrane Muc13 is suggested on
      the basis of their biochemical properties and their presence in the same locus.
      Finally, our finding that the chicken Muc13 is distributed between multiple exons
      raises the interesting possibility that the length of the PTS domain could be
      controlled by alternative splicing.

PMID- 16887039
TI  - Simultaneous gene transfer of bone morphogenetic protein (BMP) -2 and BMP-7 by in
      vivo electroporation induces rapid bone formation and BMP-4 expression.
AB  - BACKGROUND: Transcutaneous in vivo electroporation is expected to be an effective
      gene-transfer method for promoting bone regeneration using the BMP-2 plasmid
      vector. To promote enhanced osteoinduction using this method, we simultaneously
      transferred cDNAs for BMP-2 and BMP-7, as inserts in the non-viral vector pCAGGS.
      METHODS: First, an in vitro study was carried out to confirm the expression of
      BMP-2 and BMP-7 following the double-gene transfer. Next, the individual BMP-2
      and BMP-7 plasmids or both together were injected into rat calf muscles, and
      transcutaneous electroporation was applied 8 times at 100 V, 50 msec. RESULTS: In
      the culture system, the simultaneous transfer of the BMP-2 and BMP-7 genes led to
      a much higher ALP activity in C2C12 cells than did the transfer of either gene
      alone. In vivo, ten days after the treatment, soft X-ray analysis showed that
      muscles that received both pCAGGS-BMP-2 and pCAGGS-BMP-7 had better-defined
      opacities than those receiving a single gene. Histological examination showed
      advanced ossification in calf muscles that received the double-gene transfer. BMP
      4 mRNA was also expressed, and RT-PCR showed that its level increased for 3 days
      in a time-dependent manner in the double-gene transfer group.
      Immunohistochemistry confirmed that BMP-4-expressing cells resided in the matrix
      between muscle fibers. CONCLUSION: The simultaneous transfer of BMP-2 and BMP-7
      genes using in vivo electroporation induces more rapid bone formation than the
      transfer of either gene alone, and the increased expression of endogenous BMP-4
      suggests that the rapid ossification is related to the induction of BMP-4.

PMID- 16887040
TI  - Older adults' attitudes about continuing cancer screening later in life: a pilot
      study interviewing residents of two continuing care communities.
AB  - BACKGROUND: Individualized decision making has been recommended for cancer
      screening decisions in older adults. Because older adults' preferences are
      central to individualized decisions, we assessed older adults' perspectives about
      continuing cancer screening later in life. METHODS: Face to face interviews with
      116 residents age 70 or over from two long-term care retirement communities.
      Interview content included questions about whether participants had discussed
      cancer screening with their physicians since turning age 70, their attitudes
      about information important for individualized decisions, and their attitudes
      about continuing cancer screening later in life. RESULTS: Forty-nine percent of
      participants reported that they had an opportunity to discuss cancer screening
      with their physician since turning age 70; 89% would have preferred to have had
      these discussions. Sixty-two percent believed their own life expectancy was not
      important for decision making, and 48% preferred not to discuss life expectancy.
      Attitudes about continuing cancer screening were favorable. Most participants
      reported that they would continue screening throughout their lives and 43% would
      consider getting screened even if their doctors recommended against it. Only 13%
      thought that they would not live long enough to benefit from cancer screening
      tests. Factors important to consider stopping include: age, deteriorating or poor
      health, concerns about the effectiveness of the tests, and doctors
      recommendations. CONCLUSION: This select group of older adults held positive
      attitudes about continuing cancer screening later in life, and many may have had
      unrealistic expectations. Individualized decision making could help clarify how
      life expectancy affects the potential survival benefits of cancer screening.
      Future research is needed to determine whether educating older adults about the
      importance of longevity in screening decisions would be acceptable, affect older
      adults' attitudes about screening, or change their screening behavior.

PMID- 16887041
TI  - Estimating the cost of cervical cancer screening in five developing countries.
AB  - BACKGROUND: Cost-effectiveness analyses (CEAs) can provide useful information to
      policymakers concerned with the broad allocation of resources as well as to local
      decision makers choosing between different options for reducing the burden from a
      single disease. For the latter, it is important to use country-specific data when
      possible and to represent cost differences between countries that might make one
      strategy more or less attractive than another strategy locally. As part of a CEA
      of cervical cancer screening in five developing countries, we supplemented
      limited primary cost data by developing other estimation techniques for direct
      medical and non-medical costs associated with alternative screening approaches
      using one of three initial screening tests: simple visual screening, HPV DNA
      testing, and cervical cytology. Here, we report estimation methods and results
      for three cost areas in which data were lacking. METHODS: To supplement direct
      medical costs, including staff, supplies, and equipment depreciation using
      country-specific data, we used alternative techniques to quantify cervical
      cytology and HPV DNA laboratory sample processing costs. We used a detailed
      quantity and price approach whose face validity was compared to an adaptation of
      a US laboratory estimation methodology. This methodology was also used to project
      annual sample processing capacities for each laboratory type. The cost of sample
      transport from the clinic to the laboratory was estimated using spatial models. A
      plausible range of the cost of patient time spent seeking and receiving screening
      was estimated using only formal sector employment and wages as well as using both
      formal and informal sector participation and country-specific minimum wages. Data
      sources included primary data from country-specific studies, international
      databases, international prices, and expert opinion. Costs were standardized to
      year 2000 international dollars using inflation adjustment and purchasing power
      parity. RESULTS: Cervical cytology laboratory processing costs were I$1.57-3.37
      using the quantity and price method compared to I$1.58-3.02 from the face
      validation method. HPV DNA processing costs were I$6.07-6.59. Rural laboratory
      transport costs for cytology were I$0.12-0.64 and I$0.14-0.74 for HPV DNA
      laboratories. Under assumptions of lower resource efficiency, these estimates
      increased to I$0.42-0.83 and I$0.54-1.06. Estimates of the value of an hour of
      patient time using only formal sector participation were I$0.07-4.16, increasing
      to I$0.30-4.80 when informal and unpaid labor was also included. The value of
      patient time for traveling, waiting, and attending a screening visit was I$0.68
      17.74. With the total cost of screening for cytology and HPV DNA testing ranging
      from I$4.85-40.54 and I$11.30-48.77 respectively, the cost of the laboratory
      transport, processing, and patient time accounted for 26-66% and 33-65% of the
      total costs. From a payer perspective, laboratory transport and processing
      accounted for 18-48% and 25-60% of total direct medical costs of I$4.11-19.96 and
      I$10.57-28.18 respectively. CONCLUSION: Cost estimates of laboratory processing,
      sample transport, and patient time account for a significant proportion of total
      cervical cancer screening costs in five developing countries and provide
      important inputs for CEAs of alternative screening modalities.

PMID- 16887043
TI  - Population dynamics of sporogony for Plasmodium vivax parasites from western
      Thailand developing within three species of colonized Anopheles mosquitoes.
AB  - BACKGROUND: The population dynamics of Plasmodium sporogony within mosquitoes
      consists of an early phase where parasite abundance decreases during the
      transition from gametocyte to oocyst, an intermediate phase where parasite
      abundance remains static as oocysts, and a later phase where parasite abundance
      increases during the release of progeny sporozoites from oocysts. Sporogonic
      development is complete when sporozoites invade the mosquito salivary glands. The
      dynamics and efficiency of this developmental sequence were determined in
      laboratory strains of Anopheles dirus, Anopheles minimus and Anopheles
      sawadwongporni mosquitoes for Plasmodium vivax parasites circulating naturally in
      western Thailand. METHODS: Mosquitoes were fed blood from 20 symptomatic Thai
      adults via membrane feeders. Absolute densities were estimated for
      macrogametocytes, round stages (= female gametes/zygotes), ookinetes, oocysts,
      haemolymph sporozoites and salivary gland sporozoites. From these census data,
      five aspects of population dynamics were analysed; 1) changes in life-stage
      prevalence during early sporogony, 2) kinetics of life-stage formation, 3)
      efficiency of life-stage transitions, 4) density relationships between successive
      life-stages, and 5) parasite aggregation patterns. RESULTS: There was no
      difference among the three mosquito species tested in total losses incurred by P.
      vivax populations during early sporogony. Averaged across all infections,
      parasite populations incurred a 68-fold loss in abundance, with losses of ca. 19
      fold, 2-fold and 2-fold at the first (= gametogenesis/fertilization), second (=
      round stage transformation), and third (= ookinete migration) life-stage
      transitions, respectively. However, total losses varied widely among infections,
      ranging from 6-fold to over 2,000-fold loss. Losses during
      gametogenesis/fertilization accounted for most of this variability, indicating
      that gametocytes originating from some volunteers were more fertile than those
      from other volunteers. Although reasons for such variability were not determined,
      gametocyte fertility was not correlated with blood haematocrit, asexual
      parasitaemia, gametocyte density or gametocyte sex ratio. Round stages and
      ookinetes were present in mosquito midguts for up to 48 hours and development was
      asynchronous. Parasite losses during fertilization and round stage
      differentiation were more influenced by factors intrinsic to the parasite and/or
      factors in the blood, whereas ookinete losses were more strongly influenced by
      mosquito factors. Oocysts released sporozoites on days 12 to 14, but even by day
      22 many oocysts were still present on the midgut. The per capita production was
      estimated to be approximately 500 sporozoites per oocyst and approximately 75% of
      the sporozoites released into the haemocoel successfully invaded the salivary
      glands. CONCLUSION: The major developmental bottleneck in early sporogony
      occurred during the transition from macrogametocyte to round stage. Sporozoite
      invasion into the salivary glands was very efficient. Information on the natural
      population dynamics of sporogony within malaria-endemic areas may benefit
      intervention strategies that target early sporogony (e.g., transmission blocking
      vaccines, transgenic mosquitoes).

PMID- 16887042
TI  - Efficient generation of double heterologous promoter controlled oncolytic
      adenovirus vectors by a single homologous recombination step in Escherichia coli.
AB  - BACKGROUND: Oncolytic adenoviruses are promising agents for the multimodal
      treatment of cancer. However, tumor-selectivity is crucial for their
      applicability in patients. Recent studies by several groups demonstrated that
      oncolytic adenoviruses with tumor-/tissue-specific expression of the E1 and E4
      genes, which are pivotal for adenoviral replication, have a specificity profile
      that is superior to viruses that solely target the expression of E1 or E4 genes.
      Presently the E1 and E4 regions are modified in a time consuming sequential
      fashion. RESULTS: Based on the widely used adenoviral cloning system AdEasy we
      generated a novel transfer vector that allows efficient and rapid generation of
      conditionally replication-competent adenovirus type 5 based vectors with the
      viral E1 and E4 genes under the transcriptional control of heterologous
      promoters. For insertion of the promoters of interest our transfer vector has two
      unique multiple cloning sites. Additionally, our shuttle plasmid allows encoding
      of a transgene within the E1A transcription unit. The modifications, including E1
      mutations, are introduced into the adenoviral genome by a single homologous
      recombination step in Escherichia coli. Subsequently infectious viruses are
      rescued from plasmids. As a proof-of-concept we generated two conditionally
      replication-competent adenoviruses Ad.Ki x COX and Ad.COX x Ki with the promoters
      of the Ki-67 protein and the cyclooxygenase-2 (COX-2) driving E1 and E4 and vice
      versa. CONCLUSION: We demonstrated with our cloning system efficient generation
      of double heterologous promoter controlled oncolytic adenoviral vectors by a
      single homologous recombination step in bacteria. The generated viruses showed
      preferential replication in tumor cells and in a subcutaneous HT-29 colon cancer
      xenograft model the viruses demonstrated significant oncolytic activity
      comparable with dl327.

PMID- 16887044
TI  - G-InforBIO: integrated system for microbial genomics.
AB  - BACKGROUND: Genome databases contain diverse kinds of information, including gene
      annotations and nucleotide and amino acid sequences. It is not easy to integrate
      such information for genomic study. There are few tools for integrated analyses
      of genomic data, therefore, we developed software that enables users to handle,
      manipulate, and analyze genome data with a variety of sequence analysis programs.
      RESULTS: The G-InforBIO system is a novel tool for genome data management and
      sequence analysis. The system can import genome data encoded as eXtensible Markup
      Language documents as formatted text documents, including annotations and
      sequences, from DNA Data Bank of Japan and GenBank encoded as flat files. The
      genome database is constructed automatically after importing, and the database
      can be exported as documents formatted with eXtensible Markup Language or tab
      deliminated text. Users can retrieve data from the database by keyword searches,
      edit annotation data of genes, and process data with G-InforBIO. In addition,
      information in the G-InforBIO database can be analyzed seamlessly with nine
      different software programs, including programs for clustering and homology
      analyses. CONCLUSION: The G-InforBIO system simplifies genome analyses by
      integrating several available software programs to allow efficient handling and
      manipulation of genome data. G-InforBIO is freely available from the download
      site.

PMID- 16887045
TI  - Absence of erythrocyte sequestration in a case of babesiosis in a splenectomized
      human patient.
AB  - BACKGROUND: The importance of vascular occlusion in the pathogenesis of human
      haemoprotozoal disease is unresolved. METHODS: Giemsa-stained tissue sections
      from a human case of Babesia microti infection in a splenectomized patient with
      chronic lymphocytic leukaemia and colon cancer were examined to ascertain the
      distribution of parasitized erythrocytes within the vascular lumen. RESULTS: No
      evidence of sequestration was observed. CONCLUSION: This first report on the
      vascular location of B. microti in human tissue suggests that severe multi-organ
      failure due to babesiosis is independent of sequestration of parasitized
      erythrocytes. A similar pathogenesis may also cause multi-organ failure in other
      intraerythrocytic protozoal infections, including falciparum malaria.

PMID- 16887046
TI  - The mu-opioid receptor gene and smoking initiation and nicotine dependence.
AB  - The gene encoding the mu-opioid receptor (OPRM1) is reported to be associated
      with a range of substance dependence. Experiments in knockout mice indicate that
      the mu-opioid receptor may mediate reinforcing effects of nicotine. In humans,
      opioid antagonist naltrexone may reduce the reinforcing effects of tobacco
      smoking. Additionally, the OPRM1 gene is located in a region showing linkage to
      nicotine dependence. The OPRM1 is thus a plausible candidate gene for smoking
      behavior. To investigate whether OPRM1 contributes to the susceptibility of
      smoking initiation and nicotine dependence, we genotyped 11 SNPs in the gene for
      688 Caucasian subjects of lifetime smokers and nonsmokers. Three SNPs showed
      nominal significance for smoking initiation and one reached significance for
      nicotine dependence. The global test for three-marker (rs9479757-rs2075572
      rs10485057) haplotypes was significant for smoking initiation (p = 0.0022). The
      same three-marker haplotype test was marginal (p = 0.0514) for nicotine
      dependence. These results suggest that OPRM1 may be involved in smoking
      initiation and nicotine dependence.

PMID- 16887047
TI  - Osteoid osteoma of the ethmoid bone associated with dacryocystitis.
AB  - BACKGROUND: Osteoid osteomas (OO) are small, benign osteoblastic lesions. Ethmoid
      bone OO has been very rarely reported so far. CASE PRESENTATION: We report a case
      of a 16-year-old boy suffering from persistent epiphora and a mild pain in the
      area of median canthus, due to a bone density mass within the right ethmoid air
      cells extending to the ipsilateral right orbit. The mass was removed via an
      external ethmoidectomy approach. Histopathologic examination of the specimen set
      the diagnosis of OO. One year after the operation the patient is free of
      symptoms, while no recurrence occurred. CONCLUSION: A case of ethmoid bone OO
      associated with dacryocystitis is reported. Although benign and rare, OO should
      be considered in differential diagnosis of the ethmoid bone osteoblastic lesions.

PMID- 16887048
TI  - Claudins: emerging targets for cancer therapy.
AB  - The claudin (CLDN) family of transmembrane proteins plays a critical role in the
      maintenance of epithelial and endothelial tight junctions. In addition to their
      function in preserving the structure of tight junctions, CLDNs might also play a
      role in the maintenance of the cytoskeleton and in cell signalling.
      Interestingly, several studies have recently reported specific CLDN family
      members to be overexpressed in a wide variety of cancer types. Although their
      functional role in cancer progression remains unclear, the differential
      expression of these proteins between tumour and normal cells, in addition to
      their membrane localisation, makes them prime candidates for cancer therapy.
      Preclinical studies have shown that tumour cells overexpressing CLDNs can be
      successfully targeted via several approaches, including the use of anti-CLDN
      antibodies as well as the cytolytic enterotoxin from Clostridium perfringens.
      Further studies are needed to determine the potential systemic toxicity of this
      approach considering the ubiquitous expression of CLDNs in the body, but CLDN
      targeted therapeutics appear to have promise in the treatment of cancer.

PMID- 16887049
TI  - [Expression of various matrix metalloproteinases in mice with hyperoxia-induced
      acute lung injury].
AB  - OBJECTIVE: To investigate the role of matrix metalloproteinases (MMPs) and
      extracellular matrix metalloproteinase inducer (EMMPRIN) in the pathogenesis of
      acute lung injury induced by hyperoxia. METHODS: Fifty four mice were exposed in
      sealed cages to >98% oxygen (for 24-72 hours), and another 18 mice to room air.
      The severity of lung injury was assessed, and the expression of mRNA and protein
      of MMP-2, MMP-9 and EMMPRIN in lung tissue, after exposure for 24, 48 and 72
      hours of hyperoxia were studied by reverse transcription-polymerase chain
      reaction (RT-PCR) and immunohistochemistry. RESULTS: Hyperoxia caused acute lung
      injury; this was accompanied by increased expression of an upregulation of MMP-2,
      MMP-9 and EMMPRIN mRNA and protein in lung tissues. CONCLUSION: Hyperoxia causes
      acute lung injury in mice; increases in MMP-2, MMP-9 and EMMPRIN may play an
      important role in the development of hyperoxia induced lung injury in mice.

PMID- 16887050
TI  - [Effect of Rho kinase on hypoxia stimulated proliferation of pulmonary arterial
      smooth muscle cells].
AB  - OBJECTIVE: To study whether Rho kinase is involved in the proliferation of
      pulmonary arterial smooth muscle cells (PASMCs) induced by hypoxia. METHODS:
      Rat's PASMCs were isolated and cultured. Methyl thiazolyl tetrazolium (MTT) was
      used to determine the growth of cells. The cell cycle was analyzed by flow
      cytometry. Western blot was used to assess the expression of Rho kinase. RESULTS:
      The results of MTT showed that the number of PASMCs was increased after exposure
      to low oxygen tension for 12 hours compared with PASMCs in normoxia. After
      exposure of PASMCs to hypoxia for 24 hours,the cellular proliferation peaked,and
      was higher than that of PASMCs exposed to normal oxygen tension, hypoxia and
      Y27632 (Rho kinase inhibitor) groups,then it declined when exposed for 48 hours.
      Analysis of cell cycle indicated that the ability of cell proliferation increased
      significantly in PASMCs exposed to hypoxia compared with normoxia. Rho kinase
      level was higher in PASMCs exposed to hypoxia compared with normoxia. CONCLUSION:
      Hypoxia stimulates proliferation of PASMCs and promotes PASMCs into the phase of
      mitosis. The expression of Rho kinase is increased in PASMCs that are exposed to
      hypoxia, and it shows that Rho kinase is activated by hypoxia in PASMCs. Rho
      kinase maybe involve in the proliferation of PASMCs induced by hypoxia.

PMID- 16887052
TI  - [Therapeutic effects of low molecular weight heparin and aspirin on acute lung
      injury in rat].
AB  - OBJECTIVE: To investigate the possible effects of nuclear factor-KappaB (NF
      KappaB) activation on the expression of intercellular adhesion molecular-1 (ICAM
      1) and P-selectin in murine acute lung injury (ALI) and assess the potential
      beneficial effects and mechanism of low molecular weight heparin (LMWH) and
      aspirin (ASA). METHODS: Rat ALI model was reproduced by injection of
      lipopolysaccharide into tail vein. Sixty rats were divided randomly into four
      groups (n=15): normal control group, ALI group, LMWH group and ASA group. The
      change in NF-KappaB activity in the lung to show its relation with ICAM-1 and P
      selectin was observed by immunohistochemistry. RESULTS: Compared with normal
      control group, the activity of NF-KappaB and the expression of ICAM-1 and P
      selectin increased significantly in the lung tissue of ALI group (all P<0.05).
      Compared with ALI group, the level of NF-KappaB activity and the expression of
      ICAM-1 and P-selectin were obviously down regulated, and also the pathological
      lesion and inflammatory response of lung were improved in LMWH and ASA groups.
      However, the therapeutic effects of ASA were stronger than those of LMWH (all
      P<0.05). CONCLUSION: NF-KappaB activation plays an important role in ALI. NF
      KappaB takes part in the activation of many kinds of inflammatory cells such as
      neutrophil, endothelial cells and so on, and it adjusts the genetic expression of
      ICAM-1 and P-selectin. LMWH and ASA show their beneficial effects on lung injury
      in both functional and morphological aspects. But the mechanism is different.
      LMWH can indirectly inhibit the activation of NF-KappaB, improve lung
      microcirculation and decrease the adhesion of neutrophil and platelet. ASA plays
      the role as an inhibitor of NF-KappaB activation.

PMID- 16887053
TI  - [Effect of methylprednisolone on procollagen type III of rats with acute lung
      injury].
AB  - OBJECTIVE: To observe the effect of methylprednisolone on procollagen type III of
      rats with acute lung injury (ALI) induced by endotoxin. METHODS: Forty-five rats
      were randomly divided into three groups: endotoxin group, endotoxin plus
      methylprednisolone group, and control group, with 15 rats in each group. The
      model of ALI in rat was reproduced by intravenous injection of endotoxin in the
      dose of 6 mg/kg. On 1, 3, 14 days after the onset of ALI in rats, total cell
      number, classification of polymorphonuclear neutrophil (PMN), macrophages and
      procollagen type III in serum and bronchoalveolar lavage fluid (BALF) were
      determined by radioimmunology. RESULTS: Total cell number, classification of PMN
      and macrophages in BALF as well as procollagen type III level in serum and BALF
      were obviously increased in endotoxin group on the first day, then decreased
      gradually (all P<0.01). Methylprednisolone inhibited the increase of the above
      mentioned parameters (P<0.05 or P<0.01). CONCLUSION: Methylprednisolone can
      inhibit the increase of the procollagen type III levels in serum and BALF in rats
      with acute lung injury induced by endotoxin.

PMID- 16887056
TI  - [Influence and mechanism of peroxisome proliferation activated receptor-alpha
      expression induced by WY14643 in rat lung with acute lung injury].
AB  - OBJECTIVE: To investigate the effect of WY14643 [peroxisome proliferation
      activated receptor-alpha (PPAR-alpha) activator, 4-cholro-6-(2.3-xylidino)-2
      pyrimidinylthio acetic acid] on PPAR-alpha expression in lung of acute lung
      injury (ALI) induced by lipopolysaccharide (LPS) and its mechanism. METHODS: One
      hundred and four male Wistar rats were randomly divided into four groups: control
      group, ALI group, WY14643 1 mg group and WY14643 3 mg group. Wistar rats were
      given LPS (5 mg/kg) before intratracheal challenge with WY14643 (1 mg/kg and 3
      mg/kg). Rats of all groups were sacrificed at 1, 2, 4, 8 hours after LPS
      challenge. The levels of PPAR-alpha mRNA in lung were measured by semi
      quantitative reverse transcription-polymerase chain reaction, the levels of PPAR
      alpha protein in rats lung homogenate were measured by Western blot. RESULTS: The
      levels of PPAR-alpha mRNA at 2,4 and 8 hours in WY14643 1 mg group and WY14643 3
      mg group were significantly higher than that in ALI group (P<0.05 or P<0.01). The
      levels of PPAR-alpha mRNA at all time in ALI group was significantly lower than
      that in control group (P<0.01). Meanwhile,the levels of PPAR-alpha protein at all
      time in WY14643 1 mg group and WY14643 3 mg group were significantly higher than
      that in ALI group (P<0.01). The level of PPAR-alpha mRNA at 4 hours and 8 hours
      in WY14643 1 mg group and at 2,4 and 8 hours in WY14643 3 mg group were
      significantly higher than those in control group too (P<0.05 or P<0.01).
      CONCLUSION: The expressions of PPAR-alpha mRNA and protein are all significantly
      low in the lung of rats with acute lung injury. WY14643 may upregulate the level
      of PPAR-alpha in the lung tissue in rats with acute lung injury.

PMID- 16887054
TI  - [Expression and modulation of aquaporin 5 in hyperoxia induced lung injury].
AB  - OBJECTIVE: To explore the expression and the modulation of aquaporin 5(AQP5) in
      hyperoxia induced lung injury. METHODS: Sixty four Wistar rats of 2 weeks old,
      were randomly assigned to following groups (n=8): air group, hyperoxia 3, 7, 14
      days groups, air + dexamethasone (Dex), hyperoxia 3, 7, 14 days + Dex groups. The
      rats were kept in oxygen chamber at normal pressure (O(2)> or =95%) in hyperoxia
      groups, and in normal pressure air (O(2)=21%) in room-air group, and the rats in
      Dex groups were injected with Dex (5 mg.kg(-1).d(-1)) intraperitoneally for 3
      consecutive days in room-air or hyperoxia exposure. The expression of AQP5 mRNA
      level and the location were detected by reverse transcription-polymerase chain
      reaction and immunohistochemistry respectively. RESULTS: AQP5 was strongly
      labeled in alveolar epithelial type I cells, and was also expressed in the
      secretory epithelium plasma membrane in the airway. The location of AQP5 in
      hyperoxia groups was not changed, but the expression of AQP5 mRNA had a notable
      gradual decline when the time of hyperoxia exposure was prolonged, compared to
      control group (all P<0.05). There was no difference in AQP5 mRNA level between
      hyperoxia groups and hyperoxia + Dex groups at different time points (all
      P<0.05). CONCLUSION: The significant decrease in AQP5 may be an important factor
      of pulmonary edema formation in hyperoxia-induced lung injury. Dex does not have
      effect on modulating the AQP5 expression in acute lung injury.

PMID- 16887057
TI  - [Influence of different doses of porcine pulmonary on the therapeutic effects in
      rats with oleic acid induced acute lung injury].
AB  - OBJECTIVE: To investigate the therapeutic effects and dose effect relationship of
      intratracheal instillation of different doses of porcine pulmonary surfactant
      (PPS) in rats with oleic acid (OA) induced acute lung injury (ALI). METHODS:
      Arterial blood gases and respiratory rate during the experiments, survival rate,
      lung index, total protein (TP) content in bronchoalveolar lavage fluid (BALF),
      tumor necrosis factor-alpha (TNF-alpha) level in plasma, light microscopy
      examination of lung specimens after the experiments were determined and performed
      in control group, OA (0.2 ml/kg) + saline, OA + PPS 50 mg/kg, OA+PPS 80 mg/kg,
      OA+PPS 100 mg/kg, OA+PPS 150 mg/kg, OA+PPS 200 mg/kg groups, respectively.
      RESULTS: In PPS 50 mg/kg group, arterial blood gases were improved and
      respiratory rate was reduced during the first 2 hours (P<0.05). Arterial blood
      gases and reduced breath rates respiratory rate were not improved in other PPS
      treatment groups but 4 hours-survival rate was lowered, lung index was decreased,
      protein content s in BALF and TNF-alpha level in serum were lowered, and
      pathological changes were ameliorated compared with group given saline after OA,
      especially in high dosage of PPS (150-200 mg/kg) group (P<0.05). CONCLUSION:
      Administration of PPS via trachea provides obvious effects on respiratory
      functions in rats with OA induced ALI, moreover PPS (> or =80 mg/kg) alleviates
      lung injury. There is no dose-effect relationship of PPS in PPS-treatment groups.

PMID- 16887059
TI  - [Kinetics and mechanism in bleomycin-induced murine pulmonary fibrosis model].
AB  - OBJECTIVE: To investigate the kinetics of pathogenesis of bleomycin induced
      pulmonary fibrosis and its mechanism in mice. METHODS: Thirty six male ICR mice
      were randomized as a negative control (NC) group and pulmonary fibrosis model
      (FM) groups (FMA, FMB, FMC, FMD, FME sub groups). Except for NC group, mice in
      the other groups were given bleomycin by nasal instillation. Animals in each
      group were sacrificed on day 6, 14, 21, 28 and 35, respectively. T lymphocytes
      were quantified for Th1/Th2 and Tc1/Tc2 by flow cytometry. Accumulation of
      inflammatory cells in bronchioalveolar lavage fluid (BALF) was quantified by cell
      count. The sections of the right lung were stained with either hematoxylin eosin
      (HE) or Masson trichrome. The left lung was weighed and its hydroxyproline (HYP)
      content was assayed. Multi cytokine expression in lung tissue was assayed by semi
      quantitative reverse transcription polymerase chain reaction (RT-PCR). On day 35,
      the tidal volume (V(T)), forced expiratory volume in 1 second/forced vital
      capacity (FEV 0.1/FVC), static compliance (Cst) of mice were determined before
      they were sacrificed. RESULTS: (1)The total cell number in BALF in pulmonary
      fibrosis groups was statistically significantly higher than that in NC group (all
      P<0.01), and HYP content in lung tissue in pulmonary fibrosis groups was
      statistically significantly increased than that in NC group except for group FMA
      (all P<0.01). (2)V(T) and Cst in FME group were statistically significantly
      decreased than those in NC group (both P<0.01), and FEV 0.1/FVC was statistically
      significantly increased (P<0.05). (3)Th1 and Tc1 were demonstrated as the
      dominant expression in the acute inflammatory stage; Th2 and Tc2 were the
      dominant expression in the fibrosis forming stage, and then Th1 and Tc1 were
      again the dominant expression at the terminal stage of pulmonary fibrosis.
      (4)Compared with the content of cytokine in the lung in NC group, the expression
      of transforming growth factor-beta1 (TGF-beta1) and tissue inhibitor of
      metalloproteinase-1 (TIMP-1) mRNA were significantly higher in FM groups (all
      P<0.01). CONCLUSION: The changes in lung function of bleomycin-induced pulmonary
      fibrosis in mice are typical of that of restrictive ventilatory disorder. Th2,
      Tc2 and fibrotic promoting growth factors (TGF-beta1, TIMP-1, etc.) play pivotal
      roles in the pathogenesis of pulmonary fibrotic process.

PMID- 16887060
TI  - [Effect of interferon-gamma on bleomycin induced pulmonary fibrosis in rats].
AB  - OBJECTIVE: To observe the effects of interferon-gamma (IFN-gamma) on lung injury
      induced by bleomycin and its mechanism. METHODS: Sixty-six SD rats were randomly
      divided into three group: the normal control group (group N, n=24), the bleomycin
      group (group B, n=24) and IFN-gamma treatment group (group I, n=18). The degree
      of lung injury and the concentrations of tumor necrosis factor-alpha (TNF-alpha)
      and IFN-gamma in bronchoalveolar lavage fluid (BALF) and serum were measured.
      RESULTS: The degree of lung injury in group I was severer than group B, but with
      no significant difference. The concentration of TNF-alpha in BALF on 17, 21, 28
      days and in serum on 21 and 28 days were significantly increased after IFN-gamma
      administration compared with group N and group B (all P<0.05). The concentration
      of IFN-gamma in BALF and serum increased on 21 and 28 days in group I (all
      P<0.05). CONCLUSION: IFN-gamma might aggravate lung injury induced by bleomycin,
      and it might attribute to an increase in TNF-alpha.

PMID- 16887061
TI  - [Application of bronchoscopic lung volume reduction using one-way flap device in
      sheep model of heterogeneous emphysema].
AB  - OBJECTIVE: To evaluate the effectiveness of bronchoscopic lung volume reduction
      (BLVR) using one way flap device in sheep model of heterogeneous emphysema.
      METHODS: Six 6-month sheep (weight: 20-30 kg) were treated with localized papain
      instillations to generate heterogeneous emphysema, subsequently underwent BLVR
      using one way-flap device at subsegment. Lung functional residual capacity (FRC)
      was analyzed before and 8 weeks after operation. Animals were euthanized at the 8
      week time point. Lungs were removed en bloc and inflated with a super syringe to
      look for areas of gross collapse. Samples were collected from collapsed and non
      collapsed areas, fixed in 10% buffered formalin, made paraffin section and
      stained with hematoxylin-eosin (HE) to observe morphologic change of bronchi.
      RESULTS: BLVR was well tolerated without complications, and it reduced lung
      volumes (change in residual volume 49.5%). There was no evidence of infection,
      abscess, or granuloma formation, or allergic reaction. Scar tissue, generated by
      BLVR, replaced hyperinflated lung,improved respiratory function safely and
      consistently. CONCLUSION: BLVR using one-way flap device is a minimally invasive
      procedure and the stimulus of the devices to walls of bronchi is slight,
      moreover, the technique may attain effectiveness of surgery. Therefore maybe it
      will be a perspective treatment of chronic obstructive pulmonary disease.

PMID- 16887063
TI  - [Assessment on pathophysiological indexes of acute lung injury induced by
      lipopolysaccharide in rats].
AB  - OBJECTIVE: To observe and evaluate the pathophysiological indexes of acute lung
      injury (ALI) induced by lipopolysaccharide (LPS) in rats. METHODS: Thirty-three
      Wistar rats were randomly divided into normal control group and experiment group.
      Respiratory rate , mortality, arterial blood gases, compliance and wet weight of
      right lung/body weight ratio, tumor necrosis factor-alpha (TNF-alpha) in serum
      and bronchoalveolar lavage fluid (BALF) were determined 2, 4 and 6 hours after
      injection of LPS or normal saline in both groups. RESULTS: In the experiment
      group,the following changes were found. Arterial partial pressure of oxygen
      (PaO(2)) was reduced to 69.18 mm Hg (1 mm Hg=0.133 kPa), marked blood stasis, and
      edema in lung tissues could be grossly seen and pathological examination showed
      that there was a large number of inflammation cell infiltration and edema in
      interstitial spaces with disappearance of normal construction of alveolar. There
      was also dilatation of capillaries with congestion and adherent leukocytes.
      Furthermore, compliance was decreased to 47% of the normal value, and wet weight
      of right lung/body weight ratio increased to 137% of the normal value. Blood TNF
      alpha level increased markedly in serum and BALF. CONCLUSION: Specific
      pathological changes and decreased PaO(2) over 30% of the baseline value are the
      main signs of successful reproduction of ALI model in rats. Compliance and weight
      of right lung/body weight value can also reflect the status of ALI as helpful
      indexes.

PMID- 16887064
TI  - [Changes in lymph circulation in rats with experimental disseminated
      intravascular coagulation].
AB  - OBJECTIVE: To explore changes in lymph circulation in rats with experimental
      disseminated intravascular coagulation (DIC). METHODS: Thirty-two male Wistar
      rats were randomly divided into two groups: DIC group and sham-operation group,
      with 16 rats in each group.In each group, 8 rats were used to observe the
      lymphatic circulation of intestinal mesentery, and the others were used to
      observe lymphatic dynamics. Experimental DIC model was replicated by injecting
      dextran 500 via jugular vein in Wistar rats. The changes in lymph circulation
      were observed in these rats with lymphology methods. RESULTS: During the phase of
      DIC, the contractility of mesenteric micro-lymphatic (ML), the intestinal lymph
      flux, lymphocytes output were obviously decreased, and there was a few monocytes
      in the lymph fluid, but the lymph fluid viscosity was increased. After treatment
      with normal saline (NS), the contractility of ML, the intestinal lymph flux,
      lymphocytes output were obviously increased, and there was a large amount of
      monocytes in the lymph fluid, with significant difference compared with sham
      operation group (all P<0.05). Moreover, the lymph fluid viscosity was decreased
      compared with sham-operation group (P<0.05). CONCLUSION: The disturbance in lymph
      circulation mainly includes depression of contractility of lymphatics, the
      transport function of lymph circulation, and increased lymph fluid viscosity.

PMID- 16887065
TI  - [Effect of angiotensin II and its receptor antagonist on electrophysiology and L
      type calcium current in guinea cardiac myocytes].
AB  - OBJECTIVE: To evaluate the effect of angiotensin II (Ang II) and its receptor
      antagonist on action potential duration and L-type calcium current density of
      cardiac myocytes. METHODS: Single myocyte of the ventricle in guinea was
      isolated. Action potentials were recorded using a conventional glass
      microelectrode filled with 3 mol/L KCl solution. Membrane patch clamp whole cell
      recording technique was used to investigate L-type calcium current maximum in
      holding potential of -40 mV, length of time 200 ms, command potential 0 mV.
      RESULTS: Ang II induced arrhythmia of multiple electrophysiologic mechanisms.
      Action potential amplitude, 90% of action potential duration (APD90), and resting
      membrane potential (RMP) were significantly decreased or shortened after being
      perfused Ang II for 1 minute compared with controls. 30% of action potential
      duration (APD30), 50% of action potential duration (APD50), effective refractory
      period (ERP) were also shortened significantly after perfused Ang II for 3
      minutes compared with controls. Ang II increased the L-type calcium maximum
      current density after a perfusion of 5 minutes, but losartan perfusion for 1
      minute decreased the L-type calcium maximum current density, and it further
      decreased after perfusion for 3 minutes. However, the current voltage
      relationship curve was unchanged. CONCLUSION: Ang II could decrease amplitude of
      monophasic action potential, rest membrane potential, shorten duration of
      monophasic action potential and effective refractory period, increase maximum
      current density of voltage dependent L-type calcium, and possess the effect of
      inducing arrhythmia. Losartan decreased maximum current density of voltage
      dependent L-type calcium.

PMID- 16887066
TI  - [Treatment of acute myocardial infarction with autologous bone marrow stem cells
      mobilization combined with recombinant growth factor in rat].
AB  - OBJECTIVE: To observe the regeneration cardiomyocytes and neovascularization
      after mobilizing autologous bone marrow stem cells by granulocyte colony
      stimulating factor (G-CSF) alone or G-CSF combined with recombinant human growth
      hormone (rhGH) in Wistar rats with acute myocardial infarction (AMI). METHODS:
      AMI rat model was reproduced by liquid nitrogen cryoinjury. The rats were
      randomly divided into six groups: mobilization group (N group, n=8), sham
      operation group (SO group, n=6), myocardial infarction group (MI group, n=8), G
      CSF group (G group, n=8), rhGH group (GH group, n=8) and G-CSF combined with rhGH
      group (GG group, n=8). White blood cell (WBC) count and mononuclear cells
      proportion (MNC%) in peripheral blood were determined with ABX blood cell
      analyzer to estimate bone marrow stem cells mobilization. Four weeks after
      intervention, the rats were sacrificed, their respective body and heart weight
      were obtained, and the hearts were harvested for hematoxylin and eosin (HE) and
      immunohistochemical examination. RESULTS: (1)Comparing with baseline values,
      after 6 days administration of G-CSF, the WBC and MNC% increased in N and G
      groups (both P<0.01); WBC increased (P<0.01) but no difference of MNC% in MI
      group (P>0.05); WBC and MNC% were significantly higher in G group than those in
      MI group (all P<0.05). (2)Body and heart weights in GH and GG groups were higher
      than those in SO, MI and G groups respectively (all P<0.05). The ratio of heart
      and body weight was higher in GC group than that in MI,G and SO groups (P<0.05).
      (3)There were no significant differences in infarct size among MI, G, GH, and GG
      groups (P>0.05). (4)The capillary densities were higher in G, GH and GG groups
      than those in MI and SO groups; the density in GG group was higher than that in G
      and GH groups (all P<0.01). (5)BrdU positively stained neonatal cells were
      observed in G, GH and GG groups. Of them some developed into the endothelial
      cells. BrdU and cTnI double positive stained cells were observed in G and GG
      groups, which implied these cells might have differentiated into cardiac myocyte
      like cells. CONCLUSION: (1)G-CSF can mobilize bone marrow stem cells into
      peripheral blood in normal and cardiac infarct rats. The mobilized stem cells may
      enter into the infarct zone and induce the regeneration of cardiac myocyte like
      cells and vascular endothelial cells. (2)rhGH may promote the regeneration of
      capillary in the zone of infarction, but does not induce regeneration of cardiac
      myocyte like cells. (3)The combination of G-CSF with rhGH might promote more
      capillary regeneration than either of them used alone.

PMID- 16887067
TI  - [Study on specific cellular immunity of enhance intracellular survival antigen of
      Mycobacterium tuberculosis in patients with pulmonary tuberculosis].
AB  - OBJECTIVE: To investigate the level of specific cellular immunity in patients
      with active pulmonary tuberculosis and its potential relationship with severity
      of the disease. METHODS: Thirty active pulmonary tuberculosis patients with
      positive tubercle bacilli in sputum were enrolled for the study. Immune responses
      including lymphocytes proliferation enhanced by enhance intracellular survival
      (EIS) antigen and cytokine production including interferon-gamma (IFN-gamma) and
      interleukin-10 (IL-10), were assayed. Cell proliferation was determined by methyl
      thiazolyl tetrazolium (MTT), while cytokine production was quantified by enzyme
      linked immunoadsorbent assay (ELISA). The results were compared to those of 20
      healthy individuals and 16 persons recovered from tuberculosis. RESULTS: Cell
      proliferation response and IFN-gamma production were significantly higher in
      patients convalescent from tuberculosis compared to patients with active
      pulmonary tuberculosis, EIS antigen was found to elicit a dominant Th2 cytokine
      response. CONCLUSION: Impaired Th1 immune response to EIS is observed in patients
      with active pulmonary tuberculosis. Induction of imbalance of Th1/Th2 immune
      response may be the main action of EIS, which may be a factor of pathogenesis of
      tuberculosis.

PMID- 16887076
TI  - [Laparoscopic colectomy in patients with colon carcinoma].

PMID- 16887077
TI  - [Evolution of threshold retinopathy of prematurity after argon laser treatment
      under indirect ophthalmoscopy].
AB  - BACKGROUND: We undertook this study to evaluate the long-term effects of
      threshold retinopathy of prematurity (ROP) treatment using Argon laser under
      indirect ophthalmoscopy, as well as to analyze ocular diseases in those patients.
      METHODS: This is a descriptive, observational, longitudinal and prospective study
      carried out from March 1991 to February 2005, including patients with threshold
      retinopathy of prematurity for treatment using Argon laser under indirect
      ophthalmoscopy. Related ocular diseases were also reported. Descriptive
      statistics were applied. RESULTS: Follow-up was maintained for 14 years, 6.50 +/-
      1.39 (CI 95%, p < 0.05), and 170 patients were studied. Weight was 1216.50 +/-
      152.03 g (CI 95%, p < 0.05). Retinopathy was not present in 42% (72), in stage I
      III, 46% (78), and threshold stage, 12% (20). Forty eyes were treated with Argon
      laser. After treatment, no progressive disease was found in 92.75%. We found high
      myopia in 20%, macular displacement 7.5%, strabismus 35%, retinal detachment
      (5%), optical nerve atrophy 5%, and ocular atrophy 5%. CONCLUSIONS: We were able
      to demonstrate that Argon laser treatment under indirect ophthalmoscopy has been
      effective in the control of threshold disease. The most important related ocular
      diseases were strabismus and myopia. Long-term monitoring has permitted us to
      initiate timely treatment for ocular diseases related to prematurity.

PMID- 16887078
TI  - [Evaluation of cisplatin ototoxicity by the audiometric curve in retinoblastoma].
AB  - BACKGROUND: To evaluate hearing loss severity according to Brock's gradient and
      to compare it with the audiometric curve during cisplatin treatment in children
      with retinoblastoma. METHODS: This was an observational retrospective and
      retrolective study. Twenty children with the diagnosis of retinoblastoma under
      cisplatin treatment were included. Audiometric testing was performed before
      treatment, after the second and fourth doses, and after the final dose. RESULTS:
      Decreased audition was observed in 100% of the cases. Ototoxicity can be observed
      with cumulative doses of 240 mg/m(2) and higher. No improvement in audition was
      observed and the audition loss progressed from high to medium frequencies; 15% of
      the patients showed a grade II loss of high frequencies at the end of the second
      dose. This level was observed in 95% of the cases at the end of treatment. Two
      years after completion of therapy, no patient showed auditory recovery. Area
      below the curve showed higher sensitivity to identify initial auditory loss.
      CONCLUSIONS: Evaluation of audition with Brock's gradient can be performed. The
      area under the curve is a useful method to identify minor changes in serial
      conventional audiometry.

PMID- 16887079
TI  - [Algological treatment of trigeminal neuralgia. Experience of 15 years].
AB  - BACKGROUND: We present the experience in the treatment of trigeminal neuralgia
      (TN) during 15 years in one institute, evaluating epidemiological variables and
      clinical presentation, and comparing the results obtained with different
      treatments available. METHODS: A retrospective, descriptive study was carried out
      by reviewing cases diagnosed by the Neurology Service, such as TN, and treated by
      the Pain Medicine and Palliative Care Unit of the Insituto Nacional de Ciencias
      Medicas y Nutricion "Salvador Zubiran," from January 1, 1998 to December 31,
      2003. Age, sex, type of neuralgia, anatomical site affected and intensity of pain
      were evaluated by means of the Analogue Visual Scale (AVS). The following
      treatments were evaluated (pharmacologic, surgical, and blockade of Gasser
      ganglion). Descriptive statistics, linear regression and bivariate correlation
      were used (statistical package SPSS). RESULTS: Fifty two cases were studied with
      a female predominance (2:1). Average age was 60 years. Clinical presentation most
      frequently was typical neuralgia (51.9%), right predominance (59.6%) and affected
      branch V2 (50%). In 88%, pharmacological treatment was used. The reduction of
      pain was 74% in all cases, with r-.765 for the pharmacological treatment, r-.715
      in the blockade of the Gasser ganglion, and r-.901 for surgical treatment (p <
      0.01). CONCLUSIONS: In the experience of the INCMNSZ, treatment of choice in most
      cases of TN is pharmacological, with surgical treatment useful in cases where
      vascular alterations were identified.

PMID- 16887080
TI  - [Refundoplication for failed antireflux surgery. Experience in sixteen cases].
AB  - BACKGROUND: We undertook this study to identify the main causes leading to a
      failed funduplication and to determine the feasibility and effectiveness of
      reoperation by laparoscopic approach. METHODS: A retrospective and descriptive
      study was carried out with a review of patient charts. Patients were reoperated
      for failed antireflux surgery between January 1999 and September 2004. RESULTS:
      Sixteen patient charts were reviewed, 10 men (62.5%) and 6 women (37.5%), average
      age 42.1 +/- 15.4 years (21 to 72 years). Main preoperative symptoms were severe
      reflux in seven patients (43.7%), severe dysphagia in five (31.3%), and dysphagia
      and pain in four (25%). Thirteen patients (81%) had previous Nissen laparoscopic
      funduplication (NL), one (6%) open Nissen (ON) and two (13%) open Toupet (OT).
      Four patients were reoperated with open surgery (two Nissen and two Toupet), and
      12 laparoscopically (11 Nissen and 1 Toupet). The main causes of dysfunction were
      a) in LN: sliding of the funduplication in five patients (38%), angulation of the
      funduplication in three (23%) and others; b) in ON: sliding of the funduplication
      in one patient; and c) in OT: posterior sliding of the funduplication in two
      cases. The hospital stay for the laparoscopic group was 3.5 +/- 1 days (2 to 5
      days) and for the open group, 5.2 +/- 1.3 days (4 to 7 days, p < 0.013, Student t
      test). Morbidity 1 month postoperatively was 37.5%. Also reported were abdominal
      distention (19%), occasional distention with dysphagia (12%), reflux (6.5%), with
      0% mortality. CONCLUSIONS: Laparoscopic reoperation for failed antireflux surgery
      is feasible with an acceptable morbidity and good results.

PMID- 16887081
TI  - [Intraoperative endoscopy in laparoscopic fundoplications].
AB  - BACKGROUND: Laparoscopic fundoplications are the standard surgical treatment of
      patients with gastroesophageal reflux disorder. Adequate technique is the most
      important outcome factor. There is no standardized method to evaluate the
      procedure itself. Intraoperative endoscopy is a method to evaluate laparoscopic
      fundoplications. MATERIAL AND METHODS: This was a retrospective observational
      study of patients undergoing laparoscopic fundoplications from July 1999 to June
      2004, excluding open procedures and reoperations of previous failed laparoscopic
      fundoplications. Intraoperative endoscopy was performed during the dissection and
      suturing of the procedure to determine if correction of the technique is
      necessary. Number of changes were recorded and analyzed with Student's t-test.
      RESULTS: Three hundred patients were operated on, 23 were excluded (14
      reoperations and nine conventional laparotomies). Of the 277 patients included,
      178 were males and 99 females. Average age was 43.4 +/- 14 years (range: 12-85).
      There were 71 Toupet and 206 Nissen fundoplications. Intraoperative endoscopy
      determined correction of the technique in 77 patients with 1.69 +/- 0.96 changes;
      68 rotated and/or angled fundoplications, one rotation with distended stomach,
      one redundant gastric fundus, and seven change in the type of fundoplication from
      Nissen to Toupet because of tightness (3.7 +/- 1.1 changes, p = 0.0001) to
      achieve adequate fundoplication. CONCLUSIONS: Intraoperative endoscopy confirms
      adequate technique and prevents inadequate laparoscopic fundoplications. Further
      studies will determine if routine use is justified to prevent postoperative
      complications and to improve outcome.

PMID- 16887082
TI  - [Degenerative disease of the lumbar spine. Clinical and magnetic resonance
      imaging correlation].
AB  - BACKGROUND: Low back pain often affects the economically active population with
      repercussions in world productivity. MRI defines the diagnosis easily with high
      specificity, allowing the most adequate treatment to be initiated. We undertook
      this study to confirm the diagnostic sensitivity and specificity of MRI in the
      evaluation of degenerative lumbosacral disease with facet joint participation.
      METHODS: In a 6-month period we studied 358 patients with low back pain and/or
      sciatica due to degenerative disorders. We performed a basic evaluation on the
      clinical characteristics of pain. Plain sequences (T1 and T2) were used on axial,
      sagittal and coronal planes with MR equipment (0.5 T), evaluating the
      degenerative modifications of the lumbosacral region. RESULTS: Discal
      degeneration associated with multidirectional bulging of annulus and extrusion
      and protrusion of discal material affected mostly L4-L5 and L5-S1 levels. The
      same levels showed most degenerative changes on facet joints. The most relevant
      result in our study was articular facet joint disease present in all cases
      regardless of the association with intervertebral osteochondrosis, discal hernia
      and spinal stenosis. CONCLUSIONS: Diagnostic value of MRI in the study of low
      back pain offers a reliable evaluation with high sensitivity and specificity, in
      order to make appropriate therapeutic decisions.

PMID- 16887084
TI  - [General surgery in a rural hospital in the State of Quintana Roo, Mexico].
AB  - BACKGROUND: The general surgeon maintains extraordinary validity worldwide,
      especially in countries like the United States, Canada, India, and continents
      such as Australia and Africa. In addition to their role as a general surgeon,
      they assist with surgical pathologies in rural areas where there is generally a
      lack of technology to carry out complicated procedures. Therefore, we undertook
      this study to determine the number and type of surgical procedures carried out in
      a rural hospital with three general surgeons, as well as to determine morbidity
      and respective mortality. METHODS: The study was retrospective and longitudinal,
      using descriptive statistics during a 5.5-year period. RESULTS: During the period
      of June 1999 to December 2004, a total of 651 (100%) surgical procedures were
      carried out. There were 351 males (53%) and 300 females (47%) with average age of
      28.5 +/- 16.0 years. There were 408 (63%) minor surgical procedures accomplished
      in the operating room: 150 (45%) for females with average age of 25.8 +/- 13.8
      years old and 258 (55%) for males with average age of 27.7 +/- 15.5 years old.
      There were 243 major surgical procedures (37%): for females there were 150 (60%)
      with average age of 28.4 +/- 11.8 years old and for males there were 93 (40%)
      with average age of 29.5 +/- 16.6 years old [morbidity, six cases (0.9%) and
      mortality, two cases (0.3%)]. CONCLUSIONS: The demand for surgery in rural areas
      is not different from the surgery carried out in large cities, although there are
      limitations. It is important in this regard to adequately prepare the general
      surgeon in Mexico.

PMID- 16887083
TI  - [Use of vacuum-assisted closure in the treatment of surgical infection sites].
AB  - Surgical site infection is one of the most important health problems representing
      an increase in morbi-mortality and economical devastation for the patient. There
      have been a variety of procedures that surgeons have employed to control this
      situation, from very refined surgical procedures, advanced antimicrobial therapy
      to local therapy with alginates, hydrocolloid dressings and many others with
      active topical substances. One of the newest treatments is the VAC (Vacuum
      Assisted Closure). This therapy has been proven to be useful in wound infection
      control and we used it to carry out this study in 38 patients with wound
      infections. We present the results with this therapy in our institution.

PMID- 16887085
TI  - [Clear cell sarcoma and sentinel lymph node biopsy. Case report and literature
      review].
AB  - The procedure of sentinel node biopsy has been used previously in clear cell
      sarcoma. There are few studies reported. Due to the similar biological features
      with melanoma, this procedure can be effective. Sentinel biopsy is an option to
      detect nodal subclinical metastases. A 19-year-old man presented with ulcerated
      lesion in the fifth finger of the left hand. The biopsy reported clear cell
      sarcoma. Immunohistochemistry was positive for Vimentin and S-100. There was no
      evidence of regional disease. The sentinel lymph node biopsy, using patent blue
      and Tc-99 rhenium, was positive for metastases. Axillar dissection was carried
      out. The final report confirmed three metastasic nodes and the patient received
      adjuvant chemotherapy.

PMID- 16887087
TI  - [Acute abdomen secondary to spontaneous uterine rupture associated with
      pyometra].
AB  - A 71-year-old female with rheumatoid arthritis and chronic use of corticosteroids
      presented to the emergency room with 2 weeks of urinary symptoms, abdominal pain
      and a mass located in hypo-mesogastrium and both flanks. An X-ray film of the
      abdomen showed that bowels were displaced by the mass. Laboratory studies showed
      thrombocytosis (549,000/mm(3)) and leukocytosis (41,800/mm(3)). Several hours
      after her arrival the patient developed acute abdomen and surgery was indicated.
      A urinary catheter drained 2100 ml of urine and the abdominal mass was reduced in
      size but did not disappear. Surgery demonstrated that the urinary bladder covered
      the fundus and the anterior face of the uterus, where extensive necrosis and a 3
      cm perforation were found; 400 ml of foul-smelling pus was drained from the
      uterine cavity. Due to necrosis, a hysterectomy was performed. The
      histopathological report indicated necrosis, atrophic cervicitis and
      endometritis; pus culture developed Escherichia coli and Proteus vulgaris.
      Despite administration of broad-spectrum antibiotics, the patient developed
      severe sepsis and died 11 days postoperatively. During a literature review, only
      one similar case was found. Acute abdomen due to uterine perforation secondary to
      pyometra and associated with chronic use of corticosteroids is a rare
      complication.

PMID- 16887086
TI  - [Myocardial depression in the burn patient].
AB  - Myocardial depression and heart failure are frequent complications in critically
      ill burn patients. The physiopathology is complex and involves the activation of
      inflammatory pathways, ischemia-reperfusion, oxidative stress and endothelial
      lesion. Diagnosis should be made early by means of hemodynamic monitoring.
      Treatment is accomplished by inotropics that act on different pathways of the
      contractile function and immune response associated with antioxidants and
      allopurinol.

PMID- 16887088
TI  - [Importance of genetic counseling and molecular diagnosis testing in families at
      high risk for cancer].
AB  - Individuals with a family history of certain cancer types are at higher risk to
      develop a malignancy during their lifetime. The availability of the family
      history is a basic component for genetic counseling of these patients to
      determine illnesses that may affect other family members. The family history can
      help us to identify some inheritance patterns of cancer transmission among
      families. Nowadays it is possible to identify by clinical and molecular testing
      many of these familial cancer syndromes. The objective of this review is to
      provide a basis to the physician who the patient contacts first, in order to
      recognize the possibility of illnesses with a genetic transmission. This will
      allow the treating physician to refer the patient to a genetic specialist for
      possible molecular diagnosis of the illness.

PMID- 16887089
TI  - [How to win the battle against a shortage of tissues and organs for transplant?].

PMID- 16887091
TI  - Effects on accidents of periodic motor vehicle inspection in Norway.
AB  - An extensive programme of periodic motor vehicle inspection was introduced in
      Norway after 1995, when the treaty between Norway and the European Union (EU)
      granting Norway (not a member of the EU) access to the EU inner market took
      effect (The EEA treaty). This paper evaluates the effects on accidents of
      periodic inspections of cars. Trucks and buses were not included in the study.
      Negative binomial regression models were fitted to data on accidents and
      inspections created by merging data files provided by a major insurance company
      and by the Public Roads Administration. Technical defects prior to inspection
      were associated with an increased accident rate. Inspections were found to
      strongly reduce the number of technical defects in cars. Despite this, no effect
      of inspections on accident rate were found. This finding is inconsistent with the
      fact that technical defects appear to increase the accident rate; one would
      expect the repair of such defects to reduce the accident rate. Potential
      explanations of the findings in terms of behavioural adaptation among car owners
      are discussed. It is suggested that car owners adapt driving behaviour to the
      technical condition of the car and that the effect attributed to technical
      defects before inspection may in part be the result of a tendency for owners who
      are less concerned about safety to neglect the technical condition of their cars.
      These car owners might have had a higher accident rate than other car owners
      irrespective of the technical condition of the car.

PMID- 16887092
TI  - Differential detection of Blastocrithidia triatomae and Trypanosoma cruzi by
      amplification of 24salpha ribosomal RNA genes in faeces of sylvatic triatomine
      species from rural northwestern Argentina.
AB  - Flagellates indistinguishable from Trypanosoma cruzi were detected by microscopy
      in faecal samples of 2/110 Triatoma guasayana and 2/283 Triatoma garciabesi
      captured in a rural area of northwestern Argentina. Inoculation of faecal
      homogenates to mice followed by xenodiagnosis, haemoculture, histopathology and
      culture from cardiac homogenates, and PCR based on T. cruzi minicircle and
      nuclear sequences failed to detect T. cruzi infection, pointing to another
      trypanosomatidean. A PCR strategy targeted to the D7 domain of 24salpha ribosomal
      DNA genes amplified a 250 bp sequence from one T. guasayana and one T. garciabesi
      faecal lysate. Sequence analysis revealed 100% identity with 24salpha rDNA
      amplicons from Blastocrithidia triatomae obtained from faeces of reared Triatoma
      infestans bugs. Phylogenetic analysis clustered this sequence with C. fasciculata
      and L. major, separated from the Trypanosoma branch (bootstrap: 968/1000), in
      concordance with a Neighbour-joining dendrogram based on 18s rDNA sequences. This
      PCR procedure provides a rapid sensitive tool for differential diagnosis of
      morphologically similar trypanosomatids in field surveys of Chagas disease
      vectors and laboratory-reared triatomines used for xenodiagnosis.

PMID- 16887093
TI  - Effects of organic ligands, electrostatic and magnetic interactions in formation
      of colloidal and interfacial inorganic nanostructures.
AB  - This paper discusses effects of organic ligands, electrostatic and magnetic
      interactions involved in morphological control of chemically synthesized
      inorganic nanostructures including colloid and planar systems. The special
      attention was concentrated on noble metal (gold and palladium) nanoparticles and
      nanostructures formed at the gas-liquid interface. The analysis of experimental
      data showed that electrostatic and ligand-related interactions influence very
      strongly on the metal nanostructure morphology. The hydrophobicity of ligand,
      charge and binding affinity to inorganic phase are important factors influencing
      the morphology of inorganic nanostructures formed in a layer at the gas/liquid
      interface by the interfacial synthesis method. The important point of this method
      is the quasi two-dimensional character of reaction area and possibilities to
      realize ultimately thin and anisotropic dynamic monomolecular reaction system
      with two-dimensional diffusion and interactions of precursors, intermediates and
      ligands resulting in planar growth and organization of inorganic nanoparticles
      and nanostructures in the plain of Langmuir monolayer. The morphology of
      resulting inorganic nanostructures can be controlled efficiently by variations of
      growth conditions via changes in state and composition of interfacial planar
      reaction media with the same precursor, and by variations of composition of
      adjacent bulk phases. The extreme anisotropy and heterogeneity of two-dimensional
      interfacial reaction system allows creating conditions when growing inorganic
      particles floating on the aqueous phase surface interact selectively with
      hydrophobic water-insoluble ligands in interfacial monolayer or with hydrophilic
      bulk-phase ligands, or at the same time with ligands of different nature present
      in monolayer and in aqueous phase. The spatial anisotropy of interfacial reaction
      system and non-homogeneity of ligand binding to inorganic phase gives
      possibilities for growth of integrated anisotropic nanostructures with unique
      morphologies, in particularly those characterized by very high surface/volume
      ratio, high effective perimeter, and labyrinth-like structure. In a case of
      magnetic nanoparticles dispersed in colloids specific magnetic dipolar
      interactions can result in formation of chains, rings and more complex
      nanoparticulate structures or separated highly anisotropic nanoparticles.
      Theoretical considerations indicate to the importance of system dimensionality in
      relation to the energy balance which determines specific features of structure
      organization in planar charged metallic and magnetic nanostructures. For example,
      a requirement of Coulomb energy minimum, the possibility of free electron
      redistribution and strengthened attractive interactions between particles in
      metallic nanostructures can explain formation of very branchy systems with
      extremely high "effective perimeter". The obtained experimental and literature
      data show that system dimensionality, organic ligand nature along with
      electrostatic and magnetic interactions are most important factors of
      morphological control of chemically synthesized inorganic nanomaterials. The
      understanding and appropriate exploitation of these factors can be useful for
      further developments of efficient nanofabrication techniques based on colloidal
      and interfacial synthetic methods.

PMID- 16887094
TI  - Remote loading of doxorubicin into liposomes driven by a transmembrane phosphate
      gradient.
AB  - This study examines a new method for the remote loading of doxorubicin into
      liposomes. It was shown that doxorubicin can be loaded to a level of up to 98%
      into large unilamellar vesicles composed of egg phosphatidylcholine/cholesterol
      (7/3 mol/mol) with a transmembrane phosphate gradient. The different
      encapsulation efficiencies which were achieved with ammonium salts (citrate 100%,
      phosphate 98%, sulfate 95%, acetate 77%) were significantly higher as compared to
      the loading via sodium salts (citrate 54%, phosphate 52%, sulfate 44%, acetate
      16%). Various factors, including pH-value, buffer capacity, solubility of
      doxorubicin in different salt solutions and base counter-flow, which likely has
      an influence on drug accumulation in the intraliposomal interior are taken into
      account. In contrast to other methods, the newly developed remote loading method
      exhibits a pH-dependent drug release property which may be effective in tumor
      tissues. At physiological pH-value doxorubicin is retained in the liposomes,
      whereas drug release is achieved by lowering the pH to 5.5 (approximately 25%
      release at 25 degrees C or 30% at 37 degrees C within two h). The DXR release of
      liposomes which were loaded via a sulfate gradient showed a maximum of 3% at pH
      5.5.

PMID- 16887095
TI  - FTIR-microspectroscopy of prion-infected nervous tissue.
AB  - The family of transmissible spongiform encephalopathies (TSE), also termed prion
      diseases, is a group of fatal, neurodegenerative diseases characterized by the
      accumulation of a misfolded protein, the disease-associated prion protein PrPSc.
      This glycoprotein differs in secondary structure from its normal, cellular
      isoform PrPC, which is physiologically expressed mostly by neurons. Scrapie is a
      prion disease first described in the 18th century in sheep and goats, and has
      been established as a model in rodents to study the pathogenesis and pathology of
      prion diseases. Assuming a multitude of molecular parameters change in the tissue
      in the course of the disease, FTIR microspectroscopy has been proposed as a
      valuable new method to study and identify prion-affected tissues due to its
      ability to detect a variety of changes in molecular structure and composition
      simultaneously. This paper reviews and discusses results from previous FTIR
      microspectroscopic studies on nervous tissue of scrapie-infected hamsters in the
      context of histological and molecular alterations known from conventional
      pathogenesis studies. In particular, data from studies reporting on disease
      specific changes of protein structure characteristics, and also results of a
      recent study on hamster dorsal root ganglia (DRG) are discussed. These data
      include an illustration on how the application of a brilliant IR synchrotron
      light source enables the in situ investigation of localized changes in protein
      structure and composition in nervous cells or tissue due to PrPSc deposition, and
      a demonstration on how the IR spectral information can be correlated with results
      of complementary studies using immunohistochemistry and x-ray fluorescence
      techniques. Using IR microspectroscopy, some neurons exhibited a high
      accumulation of disease-associated prion protein evidenced by an increased amount
      of beta-sheet at narrow regions in or around the infected nervous cells. However,
      not all neurons from terminally diseased hamsters showed PrPSc deposition.
      Generally, the average spectral differences between all control and diseased DRG
      spectra are small but consistent as demonstrated by independent experiments.
      Along with studies on the purified misfolded prion protein, these data suggest
      that synchrotron FTIR microspectroscopy is capable of detecting the misfolded
      prion protein in situ without the necessity of immunostaining or purification
      procedures.

PMID- 16887096
TI  - Reorganization of actin filaments enhances chondrogenic differentiation of cells
      derived from murine embryonic stem cells.
AB  - Differentiation of embryonic stem cells is of great interest to developmental
      biology and regenerative medicine. This study investigated the effects of
      cytochalasin D (CD) on the distribution of actin filaments in mouse embryoid body
      (EB)-derived cells. Furthermore, CD was applied to chondrogenic medium to examine
      its chondrogenic effect. CD at a concentration of 1 microg/ml disrupted stress
      fibers in EB-derived cells. Actin filaments in treated cells reorganized into a
      peripheral pattern, and type II collagen was detected by immunocytochemistry. The
      expression of type II collagen, Sox9, and at a later time point, aggrecan was up
      regulated after CD treatment. In the CD-treated cells, Oct4 and Sox2,
      representing undifferentiation, were down-regulated as well as Sox1, AFP, and CTN
      1, representing ectoderm, endoderm, and cardiogenesis, respectively. In
      conclusion, CD treatment enhances chondrogenesis of EB-derived cells. Moreover,
      it promotes a more complete stem cell differentiation toward chondrogenesis, when
      cultured in chondrogenic medium.

PMID- 16887097
TI  - G protein-coupled receptor 12 deficiency results in dyslipidemia and obesity in
      mice.
AB  - Obesity has been proposed to be a result of an imbalance in the physiological
      system that controls and maintains the body energy homeostasis. Several G-protein
      coupled receptors (GPCRs) are involved in the regulation of energy homeostasis.
      To investigate the importance of GPCR12, mice deficient of this receptor (GPCR12
      KO) were studied regarding metabolism. Expression of GPCR12 was found primarily
      in the limbic and sensory systems, indicating its possible involvement in
      motivation, emotion together with various autonomic functions, and sensory
      information processing. GPCR12 KO mice were found to have higher body weight,
      body fat mass, lower respiratory exchange ratio (RER), hepatic steatosis, and
      were dyslipidemic. Neither food intake nor energy in faeces was affected in the
      GPCR12 KO mice. However, lower energy expenditure was found in the GPCR12 KO
      mice, which may explain the obesity. In conclusion, GPCR12 is considered
      important for the energy balance since GPCR12 KO mice develop obesity and have
      lower energy expenditure. This may be important for future drugs that target this
      receptor.

PMID- 16887098
TI  - Expression of human myoglobin in H9c2 cells enhances toxicity to added hydrogen
      peroxide.
AB  - Hydrogen peroxide (H2O2) is implicated in cardiac myocyte (CM) damage during
      myocardial ischemia-reperfusion (IR) injury. Myoglobin (Mb) is present in CM at
      significant concentrations and reacts with H2O2 to yield one- and two-electron
      oxidants that may promote myocardial injury. Paradoxically, hearts from mice
      lacking Mb are more susceptible to H2O2-induced dysfunction than the
      corresponding controls [U. Flogel, A. Godecke, L.O. Klotz, J. Schrader, Role of
      myoglobin in the anti-oxidant defense of the heart, FASEB J. 18 (2004) 1156
      1158]. We have overexpressed wild-type or Y103F variant of human Mb in cultured
      CMs to test whether Mb protects against H2O2 insult. Contrary to expectation,
      cells expressing WT or the Y103F Mb show increased mitochondrial dysfunction and
      apoptosis, and decreased ATP in response to H2O2 that follows the order native <
      Y103F Mb < WT human Mb consistent with the increasing pro-oxidant activity for
      these proteins. These data indicate that (i) Mb promotes oxidative damage to
      cultured CM and (ii) Mb may be a useful target for the design of inhibitors of
      myocardial IR injury.

PMID- 16887099
TI  - Muscle regeneration by adipose tissue-derived adult stem cells attached to
      injectable PLGA spheres.
AB  - The [corrected] use of adult stem cells for cell-based tissue engineering and
      regeneration strategies represents a promising approach for skeletal muscle
      repair. We have evaluated the combination of adipose tissue-derived adult stem
      cells (ADSCs) obtained from autologous liposuction and injectable poly(lactic-co
      glycolic acid) (PLGA) spheres for muscle regeneration. ADSCs attached to PLGA
      spheres and PLGA spheres alone were cultured in myogenic medium for 21 days and
      injected subcutaneously into the necks of nude mice. After 30 and 60 days, the
      mice were sacrificed, and newly formed tissues were analyzed by immunostaining, H
      and E staining, and RT-PCR. We found that ADSCs attached to PLGA spheres, but not
      PLGA spheres alone, were able to generate muscle tissue. These findings suggest
      that ADSCs and PLGA spheres are useful materials for muscle tissue engineering
      and that their combination can be used in clinical settings for muscle
      regeneration.

PMID- 16887100
TI  - Overexpression of adenine nucleotide translocase reduces Ca2+ signal transmission
      between the ER and mitochondria.
AB  - The adenine nucleotide translocase (ANT), besides transferring ATP from the
      mitochondrial matrix to the rest of the cell, has also been proposed to be
      involved in mitochondrial permeability transition (MPT), and accordingly in
      mitochondrial Ca2+ homeostasis. In order to assess the role of ANT in Ca2+ signal
      transmission from the endoplasmic reticulum (ER) to mitochondria, we
      overexpressed the various ANT isoforms and measured the matrix [Ca2+] ([Ca2+]m)
      increases evoked by stimulation with IP3-dependent agonists. ANT overexpression
      reduced the amplitude of the [Ca2+]m peak following Ca2+ release, an effect that
      was markedly greater for ANT-1 and ANT-3 isoforms than for ANT-2. Three further
      observations might explain these findings. First, the effect was partially
      reversed by treating the cells with cyclosporine A, suggesting the involvement of
      MPT. Second, the effect was paralleled by alterations of the 3D structure of the
      mitochondria. Finally, ANT-1 and ANT-3 overexpression also caused a reduction of
      ER Ca2+ loading that caused a marginal decrease in the cytosolic Ca2+ responses.
      Overall, these data provide evidence for the involvement of ANT-1 and ANT-3 in
      the induction of MPT and indicate the relevance of this phenomenon in ER
      mitochondria Ca2+ transfer.

PMID- 16887102
TI  - Effective attenuation of acute lung injury in vivo and the formyl peptide-induced
      neutrophil activation in vitro by CYL-26z through the phosphoinositide 3-kinase
      gamma pathway.
AB  - 5-[4-Acridin-9-ylamino]phenyl]-5-methyl-3-methylenedihydrofuran-2-one (CYL-26z)
      inhibited the polymorphonuclear leukocyte (PMNL) infiltration and protein leakage
      into the lungs in lipopolysaccharide (LPS)-induced acute lung injury (ALI) in
      mice as determined on the basis of PMNL and protein contents in bronchoalveolar
      lavage (BAL) fluid and myeloperoxidase (MPO) content in whole lung extracts. CYL
      26z also attenuated the formyl-Met-Leu-Phe (fMLP)-induced neutrophil chemotaxis
      and respiratory burst in vitro (IC(50) 8.4+/-0.9microM and 2.0+/-0.6microM,
      respectively). CYL-26z had no effect on superoxide anion (O(2)(-)) generation
      during dihydroxyfumaric acid autoxidation or on the NADPH oxidase activity in two
      cell-free systems (the arachidonic acid-induced assembly of NADPH oxidase and the
      preassembled oxidase caused by phorbol ester treatment), whereas it inhibited NaF
      induced respiratory burst. Inhibition of respiratory burst by CYL-26z was readily
      reversible by washing. Only slight, but significant, inhibition of extracellular
      signal regulated kinase (ERK) phosphorylation and p38 mitogen-activated protein
      kinase (MAPK) activation in response to fMLP by CYL-26z up to 30microM was
      obtained. CYL-26z effectively blocked the formation of phosphatidylinositol-3,4,5
      trisphosphate (PtdIns(3,4,5)P(3)) as determined by immunofluorescence microscopy
      and flow cytometry assays and the dual phosphorylation of protein kinase B
      (PKB/Akt) on S473 and T308 residues in fMLP-stimulated neutrophils. The membrane
      recruitment of p110gamma and Ras, the Ras activation, and the association between
      p110gamma and Ras were also attenuated by CYL-26z. These results indicate that
      the blockade of Ras activation by CYL-26z attenuated the downstream
      phosphoinositide 3-kinase (PI3K) gamma signaling, which is involved in
      chemoattractant-induced neutrophil chemotaxis and respiratory burst, and may have
      a beneficial anti-inflammatory effect on ALI.

PMID- 16887101
TI  - Characterization of a novel cyclic nucleotide-gated channel from zebrafish brain.
AB  - Cyclic nucleotide-gated (CNG) channels have been well characterized in the
      sensory receptors of vision and olfaction, but their characteristics in other
      tissues remain largely unknown. Here, we report characterization of a novel brain
      specific CNG channel from zebrafish. Unique among CNG channels, the transcript is
      expressed mainly in the brain. When expressed in Xenopus oocytes, the channel's
      electrophysiological properties are distinct compared to CNG channels from either
      rods (CNGA1), olfactory receptors (CNGA2), or cones (CNGA3). The channel is less
      sensitive to cAMP than cGMP (K(1/2) of 280 and 7 microM, respectively), with a
      maximum cAMP efficacy at least 80% of that with saturating levels of cGMP. The
      single-channel conductance of 58pS is larger than most other CNG channels. Like
      other CNG channels the channel is relatively nonselective among monovalent
      cations. However, unlike other CNG channels, there was rundown of the macroscopic
      current within 30-100 min after patch excision.

PMID- 16887103
TI  - Cytochrome P450 reductase dependent inhibition of cytochrome P450 2B1 activity:
      Implications for gene directed enzyme prodrug therapy.
AB  - Cytochrome P450 (P450) enzymes are often used in suicide gene cancer therapy
      strategies to convert an inactive prodrug into its therapeutic active
      metabolites. However, P450 activity is dependent on electrons supplied by
      cytochrome P450 reductase (CPR). Since endogenous CPR activity may not be
      sufficient for optimal P450 activity, the overexpression of additional CPR has
      been considered to be a valuable approach in gene directed enzyme prodrug therapy
      (GDEPT). We have analysed a set of cell lines for the effects of CPR on
      cytochrome P450 isoform 2B1 (CYP2B1) activity. CPR transfected human embryonic
      kidney 293 (HEK293) cells showed both strong CPR expression in Western blot
      analysis and 30-fold higher activity in cytochrome c assays as compared to
      parental HEK293 cells. In contrast, resorufin and 4-hydroxy-ifosfamide assays
      revealed that CYP2B1 activity was up to 10-fold reduced in CPR/CYP2B1
      cotransfected HEK293 cells as compared to cells transfected with the CYP2B1
      expression plasmid alone. Determination of ifosfamide-mediated effects on cell
      viability allowed independent confirmation of the reduction in CYP2B1 activity
      upon CPR coexpression. Inhibition of CYP2B1 activity by CPR was also observed in
      CYP2B1/CPR transfected or infected pancreatic tumour cell lines Panc-1 and Pan02,
      the human breast tumour cell line T47D and the murine embryo fibroblast cell line
      NIH3T3. A CPR mediated increase in CYP2B1 activity was only observed in the human
      breast tumour cell line Hs578T. Thus, our data reveal an effect of CPR on CYP2B1
      activity dependent on the cell type used and therefore demand a careful
      evaluation of the therapeutic benefit of combining cytochrome P450 and CPR in
      respective in vivo models in each individual target tissue to be treated.

PMID- 16887104
TI  - Embryonic expression of zebrafish AMPA receptor genes: zygotic gria2alpha
      expression initiates at the midblastula transition.
AB  - The AMPA-preferring receptors (AMPARs) mediate rapid excitatory synaptic
      transmission in the central nervous system of vertebrates. Expression profiles of
      8 AMPAR genes were studied by RT-PCR analyses to elucidate the properties of
      AMPARs during early zebrafish development. Transcripts of all AMPAR genes are
      detected at the time of fertilization, suggesting maternal transcriptions of
      zebrafish AMPAR genes. The amounts of gria1 and gria2 transcripts are several
      fold higher than that of gria3 and gria4 between 10 and 72 hpf (hour
      postfertilization). The edited gria2alpha transcript decreases during
      gastrulation period, suggesting that zygotic expression of gria2alpha begins
      around the time of midblastula transition. Relative to the amount of beta-actin,
      the amounts of AMPAR transcripts increase significantly after the completion of
      neurulation. The amounts of gria2 transcripts exceed the total amounts of the
      remaining AMPAR transcripts after 36 hpf, suggesting increases in the
      representation of low Ca2+ permeable AMPARs during neuronal maturation. Many but
      not all of the known mammalian protein-protein interaction motifs are preserved
      in the C-terminal domains (CTD) of zebrafish AMPARs. Before 16 hpf, the embryos
      express predominantly the alternative splice forms encoding longer CTD.
      Representations of the short CTD splice forms of gria2 and gria4alpha increase
      after 24 hpf, when neurulation is nearly completed.

PMID- 16887105
TI  - Phasic spike-timing-dependent plasticity of human motor cortex during walking.
AB  - Research into mechanisms for inducing long-lasting increases in human motor
      system excitability holds great promise for two prime reasons. First, the
      research may provide a better understanding of the role of cortex in human
      movement. Second, an induced increase in the excitability of the motor system
      during walking re-training following neural injury may emerge as a valuable
      therapeutic adjunct. The present study applied paired associative stimulation
      (PAS) to healthy humans during walking. PAS is based on the principles of spike
      timing-dependent plasticity. Our hypothesis predicted that PAS applied to
      tibialis anterior (TA) during walking would facilitate TA motor system
      excitability, would not be cycle-phase-specific and would not modulate motor
      system excitability of other lower limb muscles. Common peroneal nerve (CPN)
      stimulation paired with transcranial magnetic stimulation (TMS) at 0.2 Hz with an
      inter-spike interval chosen to achieve a long-lasting facilitation of TMS-induced
      responses in TA was delivered during the early swing, late swing and stance
      phases of the step cycle in three separate sessions. The amplitude of TMS-induced
      motor-evoked potentials was taken as a measure of motor system excitability. The
      PAS protocol increased the amplitude of TA responses to 130% of baseline in the
      late swing phase. A subsequent experiment conducted in two sessions revealed that
      this facilitation could be reversed to suppression if stimulus pairs with the
      same inter-spike interval were delivered in mid-swing. These novel findings
      demonstrate that spike-timing-dependent protocols modulate lower limb cortical
      circuitry during walking in a phasic manner.

PMID- 16887106
TI  - Fmrp is required for the establishment of the startle response during the
      critical period of auditory development.
AB  - Fragile X syndrome, the most common form of inherited mental retardation, is
      caused by the absence of the FMR-1 gene product FMRP. In addition to the hallmark
      cognitive defect, other symptoms are also apparent including hyperactivity,
      seizures and sensory abnormalities including a characteristic increase in
      sensitivity to auditory, tactile, visual, and olfactory stimuli. Fragile X is a
      developmental disorder with the first symptoms apparent in the first year of life
      but little is known about the role of FMRP in developmental processes. The
      sensory hyperreactivity of fragile X can be reproduced in fmr-1 knockout (KO)
      mice evident as abnormal audiogenic startle response and increased audiogenic
      seizure susceptibility. Here, we studied the onset and emergence of the startle
      deficit in fmr-1 KO mice during development. The startle response was first
      detectable at the end of the 2nd postnatal week in wild-type mice. The amplitude
      of startle response showed a substantial increase until the 4th postnatal week
      followed by a further but moderate increase up to adulthood. Expression of the
      fmr1 gene was detectable in the startle circuit before the onset and throughout
      the development of the startle response. Although the onset and amplitude of the
      startle response were not altered in fmr1 KO mice until the 3rd-4th postnatal
      week, beyond this age it failed to develop further resulting in an overall
      response deficit in adult KO mice. This indicates that although Fmrp is
      dispensable at the initial steps of startle response development, it is necessary
      for the full development of the response.

PMID- 16887107
TI  - Apoptosis of human macrophages by Flt-4 signaling: implications for
      atherosclerotic plaque pathology.
AB  - BACKGROUND: Neointimal inflammation and angiogenesis are important contributors
      of progression and destabilization of the atherosclerotic plaque. While the role
      of vascular endothelial growth factor (VEGF) and its receptors VEGF-R1 (Flt-1)
      and VEGF-R2 (Flk-1) in this process has clearly been defined, expression of the
      VEGF-R3 (Flt-4) has only been documented on lymphatic and tumor endothelium. This
      study examined Flt-4 expression in human atherosclerotic plaque and explored its
      implications for atherosclerotic disease. METHODS AND RESULTS: Carotid artery
      thrombendartherectomy specimens from 10 patients with unstable plaque were
      stained for Flt-4 and its specific growth factors VEGF-C and VEGF-D.
      Microvascular endothelial cells (MVEC) stained positive for VEGF-C and -D, but
      not for Flt-4. Interestingly, macrophages within inflammatory perivascular
      regions coexpressed Flt-4, VEGF-C and VEGF-D. In vitro studies confirmed the
      expression of Flt-4, VEGF-C and VEGF-D in human monocytes and cultured
      macrophages. Treatment of macrophages with VEGF-D induced apoptosis as determined
      by annexin V staining, by immunoblotting of activated caspase 3, and by the ratio
      of Bcl-2/Bax as well as by DNA fragmentation. Immunohistochemical studies of
      advanced human carotid atherosclerotic plaque confirmed the coexpression of Flt-4
      with activated caspase 3 and TUNEL staining in macrophages, indicating an ongoing
      apoptotic process. CONCLUSION: Human monocytes/macrophages express VEGF-C and -D
      and their receptor Flt-4 in vitro and in vivo within advanced atherosclerotic
      lesions. Flt-4, in turn, mediates monocyte/macrophage apoptosis and may this way
      alter plaque stability.

PMID- 16887108
TI  - Much ado about bone marrow stem cells: role in post-myocardial infarct repair.

PMID- 16887109
TI  - The role of intracellular zinc in chromium(VI)-induced oxidative stress, DNA
      damage and apoptosis.
AB  - Several studies have demonstrated that zinc is required for the optimal
      functioning of the skin. Changes in intracellular zinc concentrations have been
      associated with both improved protection of skin cells against various noxious
      factors as well as with increased susceptibility to external stress. Still,
      little is known about the role of intracellular zinc in hexavalent chromium
      (Cr(VI))-induced skin injury. To address this question, the effects of zinc
      deficiency or supplementation on Cr(VI)-induced cytotoxicity, oxidative stress,
      DNA injury and cell death were investigated in human diploid dermal fibroblasts
      during 48 h. Zinc levels in fibroblasts were manipulated by pretreatment of cells
      with 100 microM ZnSO4 and 4 or 25 microM zinc chelator TPEN. Cr(VI) (50, 10 and 1
      microM) was found to produce time- and dose-dependent cytotoxicity resulting in
      oxidative stress, suppression of antioxidant systems and activation of p53
      dependent apoptosis which is reported for the first time in this model in
      relation to environmental Cr(VI). Increased intracellular zinc partially
      attenuated Cr(VI)-induced cytotoxicity, oxidative stress and apoptosis by
      enhancing cellular antioxidant systems while inhibiting Cr(VI)-dependent
      apoptosis by preventing the activation of caspase-3. Decreased intracellular zinc
      enhanced cytotoxic effects of all the tested Cr(VI) concentrations, leading to
      rapid loss of cell membrane integrity and nuclear dispersion--hallmarks of
      necrosis. These new findings suggest that Cr(VI) as a model environmental toxin
      may damage in deeper regions residing skin fibroblasts whose susceptibility to
      such toxin depends among others on their intracellular Zn levels. Further
      investigation of the impact of Zn status on skin cells as well as any other cell
      populations exposed to Cr(VI) or other heavy metals is warranted.

PMID- 16887110
TI  - Bilirubin toxicity to human erythrocytes: a review.
AB  - Neonatal jaundice, a physiologic condition reflecting the interplay between
      developmentally modulated changes in bilirubin production and metabolism, affects
      virtually all newborn infants. Usually, it is an entirely benign process that is
      resolved at the end of the first week of life without treatment or sequelae.
      However, in a small percentage of neonates, unconjugated hyperbilirubinemia can
      pose a neurotoxic risk especially in the presence of aggravating conditions such
      as a diminished albumin binding capacity and/or affinity, acidosis, displacing
      drugs and prematurity. Although neuronal cells are considered the main target for
      unconjugated bilirubin (UCB) toxicity, circulating cells are also affected during
      neonatal hyperbilirubinemia. Moreover, the UCB ability to cause hemolysis shall
      further aggravate neonatal jaundice through a vicious circle. In this review, we
      summarize the most relevant data obtained by our group regarding UCB toxicity and
      the role of some risk factors for kernicterus. In order to improve the risk
      assessment of neurotoxicity it is essential to understand the underlying
      mechanisms of UCB pathophysiology.

PMID- 16887111
TI  - The basis for hyperactivity of antifreeze proteins.
AB  - Antifreeze proteins (AFPs) bind to the surface of ice crystals and lower the non
      equilibrium freezing temperature of the icy solution below its melting point. We
      have recently reported the discovery of three novel hyperactive AFPs from a
      bacterium, a primitive insect and a fish, which, like two hyperactive AFPs
      previously recognized in beetles and moths, are considerably better at depressing
      the freezing point than most fish AFPs. When cooled below the non-equilibrium
      freezing temperature, ice crystals formed in the presence of any of five
      distinct, moderately active fish AFPs grow suddenly along the c-axis. Ice
      crystals formed in the presence of any of the five evolutionarily and
      structurally distinct hyperactive AFPs remain stable to lower temperatures, and
      then grow explosively in a direction normal to the c-axis when cooled below the
      freezing temperature. We argue that this one consistent distinction in the
      behaviour of these two classes of AFPs is the key to hyperactivity. Whereas both
      AFP classes bind irreversibly to ice, the hyperactive AFPs are better at
      preventing ice growth out of the basal planes.

PMID- 16887112
TI  - A new approach for freezing of aqueous solutions under active control of the
      nucleation temperature.
AB  - An experimental setup for controlled freezing of aqueous solutions is introduced.
      The special feature is a mechanism to actively control the nucleation temperature
      via electrofreezing: an ice nucleus generated at a platinum electrode by the
      application of an electric high voltage pulse initiates the crystallization of
      the sample. Using electrofreezing, the nucleation temperature in pure water can
      be precisely adjusted to a desired value over the whole temperature range between
      a maximum temperature Tn(max) close to the melting point and the temperature of
      spontaneous nucleation. However, the presence of additives can inhibit the
      nucleus formation. The influence of hydroxyethylstarch (HES), glucose, glycerol,
      additives commonly used in cryobiology, and NaCl on Tn(max) were investigated.
      While the decrease showed to be moderate for the non-ionic additives, the
      hindrance of nucleation by ionic NaCl makes the direct application of
      electrofreezing in solutions with physiological salt concentrations impossible.
      Therefore, in the multi-sample freezing device presented in this paper, the ice
      nucleus is produced in a separate volume of pure water inside an electrode cap.
      This way, the nucleus formation becomes independent of the sample composition.
      Using electrofreezing rather than conventional seeding methods allows automated
      freezing of many samples under equal conditions. Experiments performed with model
      solutions show the reliability and repeatability of this method to start
      crystallization in the test samples at different specified temperatures. The
      setup was designed to freeze samples of small volume for basic investigations in
      the field of cryopreservation and freeze-drying, but the mode of operation might
      be interesting for many other applications where a controlled nucleation of
      aqueous solutions is of importance.

PMID- 16887113
TI  - Transmission of modified nucleosomes from the mouse male germline to the zygote
      and subsequent remodeling of paternal chromatin.
AB  - Rapidly after gamete fusion, the sperm nucleus loses its specific chromatin
      conformation and the DNA is repopulated with maternally derived nucleosomes. We
      evaluated the nature of paternally derived nucleosomes and the dynamics of sperm
      chromatin remodeling in the zygote directly after gamete fusion. We observed
      histone H4 acetylated at K8 or K12 already prior to full decondensation of the
      sperm nucleus, suggesting that these marks are transmitted by the spermatozoon.
      Tracking down the origin of H4K8ac and H4K12ac during spermiogenesis revealed the
      retention of nucleosomes with these modifications in the chromocenter of
      elongating spermatids. We show that sperm constitutive heterochromatin is
      enriched for nucleosomes carrying specific histone modifications which are
      transmitted to the zygote. Our results suggest an epigenetic mechanism for
      inheritance of chromosomal architecture. Furthermore, up to pronucleus formation,
      histone acetylation and phosphorylation build up in a cascade-like fashion in the
      paternal chromatin. After formation of the pronucleus, a subset of these marks is
      removed from the heterochromatin, which suggests a reestablishment of the
      euchromatin-heterochromatin partition.

PMID- 16887114
TI  - Drosophila Rho-kinase (DRok) is required for tissue morphogenesis in diverse
      compartments of the egg chamber during oogenesis.
AB  - The Rho-kinases are widely utilized downstream targets of the activated Rho
      GTPase that have been directly implicated in many aspects of Rho-dependent
      effects on F-actin assembly, acto-myosin contractility, and microtubule
      stability, and consequently play an essential role in regulating cell shape,
      migration, polarity, and division. We have determined that the single closely
      related Drosophila Rho-kinase ortholog, DRok, is required for several aspects of
      oogenesis, including maintaining the integrity of the oocyte cortex, actin
      mediated tethering of nurse cell nuclei, "dumping" of nurse cell contents into
      the oocyte, establishment of oocyte polarity, and the trafficking of oocyte yolk
      granules. These defects are associated with abnormalities in DRok-dependent actin
      dynamics and appear to be mediated by multiple downstream effectors of activated
      DRok that have previously been implicated in oogenesis. DRok regulates at least
      one of these targets, the membrane cytoskeletal cross-linker DMoesin, via a
      direct phosphorylation that is required to promote localization of DMoesin to the
      oocyte cortex. The collective oogenesis defects associated with DRok deficiency
      reveal its essential role in multiple aspects of proper oocyte formation and
      suggest that DRok defines a novel class of oogenesis determinants that function
      as key regulators of several distinct actin-dependent processes required for
      proper tissue morphogenesis.

PMID- 16887116
TI  - Housing and health counselling: preliminary results of a new medical referral
      system in France.
AB  - STUDY OBJECTIVES: Since 2002, a new unique service is available to physicians in
      southeast France. They may ask for a housing environmental inspection for their
      patients when they feel that the indoor environment has a negative influence on
      health status. This telephone survey was designed to evaluate the efficacy of
      this service. DESIGN: During this time period, 328 such housing environmental
      inspections have been performed. The protocol of these inspections included a
      detailed questionnaire and environmental sampling for mold identification, mite
      allergen evaluation and, in selected cases, measurement of volatile organic
      compounds (VOC). Inspections were performed by trained technicians. From April to
      September 2005, we performed a telephone interview survey, using a structured
      questionnaire, to evaluate the reported outcome. RESULTS: Main defects identified
      in houses were mold infestation (44%), mite contamination (32%), and VOC exposure
      (9%) from new furniture, repairs performed and hobbies. Substantial repairs,
      including carpentry, wall floors and ceilings repairs, mold decontamination, and
      plumbing, had been performed in 59.4% of those houses. Full compliance, partial
      compliance, and no compliance by the occupant with the recommendations provided
      by the housing environmental inspectors were 50%, 20%, and 30%, respectively.
      Reasons for non-compliance included moving, time, and money constraints. When
      rating the efficacy of the service, total, almost total, and partial
      effectiveness was reported by the families to be 3%, 31%, and 56%, respectively.
      CONCLUSION: This type of service holds great promise for patients as well as for
      physicians and should be investigated further by measuring physician-diagnosed
      health outcome and using cost-benefit analysis.

PMID- 16887115
TI  - Gata6 is an important regulator of mouse pancreas development.
AB  - Gata4, Gata5, and Gata6 represent a subfamily of zinc-finger transcriptional
      regulators that are important in the development and differentiation of numerous
      tissues, including many endodermally-derived organs. We demonstrate that Gata4
      and Gata6 have overlapping expression patterns in the early pancreatic
      epithelium. Later, Gata4 becomes restricted to exocrine tissue and Gata6 becomes
      restricted to a subset of endocrine cells. In addition, we show Gata6, but not
      Gata4, physically interacts with Nkx2.2, an essential islet transcription factor.
      To begin determining the roles that Gata4 and Gata6 play during pancreatic
      development, we expressed Gata4-Engrailed and Gata6-Engrailed dominant repressor
      fusion proteins in the pancreatic epithelium and in the islet. At e17.5,
      transgenic Gata6-Engrailed embryos exhibit two distinct phenotypes: a complete
      absence of pancreas or a reduction in pancreatic tissue. In the embryos that do
      form pancreas, there is a significant reduction of all pancreatic cell types,
      with the few differentiated endocrine cells clustered within, or in close
      proximity to, enlarged ductal structures. Conversely, the majority of transgenic
      Gata4-Engrailed embryos do not have a pancreatic phenotype. This study suggests
      that Gata6 is an important regulator of pancreas specification.

PMID- 16887117
TI  - Effect of tamsulosin on spontaneous bladder contraction in conscious rats with
      bladder outlet obstruction: comparison with effect on intraurethral pressure.
AB  - We investigated the effect of tamsulosin, an alpha(1)-adrenoceptor antagonist, on
      bladder function, especially spontaneous bladder contractions before micturition
      (premicturition contraction), in conscious rats with bladder outlet obstruction
      induced by partial urethral ligation, and compared the results with the effect on
      intraurethral pressure response in anesthetized rats. In obstructed rats, the
      alpha(1)-adrenoceptor antagonists tamsulosin, naftopidil and urapidil and non
      selective alpha-adrenoceptor antagonist phentolamine inhibited premicturition
      contractions in a dose-dependent fashion. In contrast, yohimbine, an alpha(2)
      adrenoceptor antagonist, and atropine, a muscarinic receptor antagonist, hardly
      inhibited them. Tamsulosin and urapidil showed clearly inhibitory effects on
      increases in intraurethral pressure induced by phenylephrine, an alpha(1)
      adrenoceptor agonist, in the same dose range as that at which they inhibited
      premicturition contractions, whereas naftopidil required somewhat higher doses to
      inhibit increases in intraurethral pressure than those at which it inhibited
      premicturition contractions. In conclusion, premicturition contractions observed
      in obstructed rats were sensitive to alpha(1)-adrenoceptor antagonists, but not
      to alpha(2)-adrenoceptor or muscarinic receptor antagonists. Tamsulosin was shown
      to be effective against both premicturition contraction and intraurethral
      pressure response in the same dose range in rats. These results partly support
      the fact that tamsulosin has improved storage symptoms as well as voiding
      symptoms in patients with lower urinary tract symptoms associated with bladder
      outlet obstruction by blocking alpha(1)-adrenoceptors.

PMID- 16887118
TI  - Altered synaptic function in Alzheimer's disease.
AB  - Alzheimer's disease is the leading cause of dementia in the elderly, presenting
      itself clinically by progressive loss of memory and learning. Since synaptic
      density correlates more closely with cognitive impairment than any other
      pathological lesion observable in the disease pathology, an increased
      understanding of the mechanisms behind synaptic disconnection is of vital
      importance. Our lab investigated the neurotransmitter-specific status of distinct
      cortical presynaptic bouton populations in various transgenic mouse models of the
      Alzheimer's-like amyloid pathology in order to assess their involvement
      throughout the progression of the pathology. These studies have revealed that the
      amyloid pathology appears to progress in a neurotransmitter-specific manner where
      the cholinergic terminals appear most vulnerable, followed by the glutamatergic
      terminals and finally by the somewhat more resilient GABAergic terminals. This
      review will discuss additional studies which also provide evidence of a
      neurotransmitter-specific pathology as well as comment on the potential
      explanations for the observed vulnerabilities, touching upon metabolic demand,
      trophic support and receptor mediated activation.

PMID- 16887119
TI  - A functional Jak2 tyrosine kinase domain is essential for mouse development.
AB  - Jak2 is a member of the Janus family of tyrosine kinases and is involved in
      cytokine signaling. As a part of a study to determine biological functions of
      Jak2, we used molecular modeling to identify W1038 as a residue that is critical
      for tyrosine kinase function. Mutation of W1038, in tandem with E1046, generates
      a dominant-negative form of the Jak2 protein. Mice that were engineered to
      express two copies of this dominant-negative Jak2 protein died in utero.
      Additionally, heterozygous mice expressing Jak2 with kinase activity that is
      moderately reduced when compared to wild-type activity appear phenotypically
      normal. Collectively, these data suggest that Jak2 kinase activity is essential
      for normal mammalian development.

PMID- 16887120
TI  - p75NTR enhances PC12 cell tumor growth by a non-receptor mechanism involving
      downregulation of cyclin D2.
AB  - p75NTR is a member of the tumor necrosis superfamily of proteins which is
      variably associated with induction of apoptosis and proliferation. Cyclin D2 is
      one of the mediators of cellular progression through G1 phase of the cell cycle.
      The present study demonstrates the inverse relationship between expression of
      cyclin D2 and expression of p75NTR in PC12 cells. Induction of p75NTR expression
      in p75NTR-negative PC12 cells results in downregulation of cyclin D2; suppression
      of p75NTR expression with siRNA in native PC12 cells results in upregulation of
      cyclin D2. The effects of p75NTR on cyclin D2 expression are mimicked in p75NTR
      negative cells by transfection with the intracellular domain of p75NTR. Cyclin-D2
      positive PC12 cell cultures grow more slowly than cyclin-D2-negative cultures,
      and induction of expression of cyclin D2 slows the culture growth rate of cyclin
      D2-negative cells. Finally, subcutaneous murine xenografts of cyclin-D2-negative,
      p75NTR-positive PC12 cells more frequently and more rapidly produce tumors than
      the analogous xenografts of cyclin-D2-positive, p75NTR-negative cells. These
      results suggest that p75NTR suppresses cyclin D2 expression in PC12 cells by a
      mechanism distinct from its function as a nerve growth factor receptor and that
      cyclin D2 expression decreases cell culture and xenografted tumor growth.

PMID- 16887121
TI  - Polyploidization increases the sensitivity to DNA-damaging agents in mammalian
      cells.
AB  - Polyploidization occurs during normal development as well as during
      tumorigenesis. In this study, we investigated if the responses to genotoxic
      stress in cancer cells are influenced by the ploidy. Prolonged treatment of Hep3B
      cells with the spindle inhibitor nocodazole resulted in mitotic slippage,
      followed by re-replication of the DNA to produce polyploids. Reintroduction of
      p53 restored the checkpoints and suppressed polyploidization. Remarkably, a
      stable tetraploidy cell line could be generated from Hep3B by a transient
      nocodazole treatment followed by a period of recovery. Using this novel
      tetraploid system, we found that tetraploidization increased the cell volume
      without significantly affecting the cell cycle. Although tetraploidization was
      accompanied by an increase in centrosome number, the majority of mitoses in the
      tetraploid cells remained bipolar. Polyploidization sensitized cells to genotoxic
      stress inflicted by ionizing radiation and topoisomerase inhibitors without
      affecting the sensitivity to spindle inhibitors. Accordingly, more gamma-H2AX
      foci were induced by radiation in tetraploids than in normal Hep3B cells.
      Likewise, primary tetraploid human fibroblasts displayed higher gamma-H2AX foci
      formation than diploid human fibroblasts. An implication for chemotherapy is that
      some cancer cells can be sensitized to genotoxic agents by a preceding step that
      induces polyploidization.

PMID- 16887122
TI  - Interfering polysialyltransferase ST8SiaII/STX mRNA inhibits neurite growth
      during early hippocampal development.
AB  - Polysialic acid (PSA) attached to NCAM is involved in cell-cell interactions
      participating in structural and functional plasticity of neuronal circuits. Two
      polysialyltransferases, ST8SiaII/STX and ST8SiaIV/PST, polysialylate NCAM. We
      previously suggested that ST8SiaII/STX is the key enzyme for polysialylation in
      hippocampus. Here, polysialyltransferase mRNA interference experiments showed
      that, knock down of ST8SiaIV/PST transcripts did not affect PSA expression, but
      PSA was almost absent from neuronal surfaces when ST8SiaII/STX mRNA was
      interfered. Non-polysialylated neurons bore a similar number of neurites per cell
      than polysialylated neurons. However, non-polysialylated processes were shorter
      and a lower density of synaptophysin clusters accompanied this reduced neuritic
      growth. Therefore, ST8SiaII/STX expression is essential to allow a correct
      neuritic development at initial stages of hippocampus ontogeny.

PMID- 16887123
TI  - Extended-release niacin raises adiponectin and leptin.
AB  - BACKGROUND: The lipid-lowering drug niacin has attracted renewed interest because
      it raises HDL-cholesterol and because it has recently been found to slow down the
      progression of intima media thickness in patients with coronary heart disease.
      Since niacin acts on adipocytes, we investigated its impact on adipokines and on
      some functions attributed to adipokines. METHODS AND RESULTS: In a randomized,
      placebo-controlled, double-blind study 30 men with the metabolic syndrome were
      treated for 6 weeks with 1500 mg extended-release niacin (n=20) or a placebo
      (n=10). Adiponectin increased by 56% (p<0.001) and leptin by 26.8% (p<0.012).
      Resistin, TNF-alpha, IL-6, and high sensitive CRP remained unchanged. In spite of
      the increase in adiponectin there was no improvement in endothelial function. The
      HOMA index actually deteriorated by 42% (p<0.014). CONCLUSION: Short-term
      treatment with extended-release niacin causes a pronounced increase in
      adiponectin but fails to improve atheroprotective functions attributed to
      adiponectin, such as insulin sensitivity, anti-inflammation and endothelial
      function.

PMID- 16887125
TI  - Measurement of local strain on cell membrane at initiation point of calcium
      signaling response to applied mechanical stimulus in osteoblastic cells.
AB  - In adaptive bone remodeling, it is believed that bone cells such as osteoblasts,
      osteocytes and osteoclasts can sense mechanical stimuli and modulate their
      remodeling activities. However, the mechanosensing mechanism by which these cells
      sense mechanical stimuli and transduce mechanical signals into intracellular
      biochemical signals is still not clearly understood. From the viewpoint of cell
      biomechanics, it is important to clarify the mechanical conditions under which
      the cellular mechanosensing mechanism is activated. The aims of this study were
      to evaluate a mechanical condition, that is, the local strain on the cell
      membrane, at the initiation point of the intracellular calcium signaling response
      to the applied mechanical stimulus in osteoblast-like MC3T3-E1 cells, and to
      investigate the effect of deformation velocity on the characteristics of the
      cellular response. To apply a local deformation to a single cell, a glass
      microneedle was directly indented to the cell and moved horizontally on the cell
      membrane. To observe the cellular response and the deformation of the cell
      membrane, intracellular calcium ions and the cell membrane were labeled using
      fluorescent dyes and simultaneously observed by confocal laser scanning
      microscopy. The strain distribution on the cell membrane attributable to the
      applied local deformation and the strain magnitude at the initiation point of the
      calcium signaling responses were analyzed using obtained fluorescence images.
      From two-dimensionally projected images, it was found that there is a local
      compressive strain at the initiation point of calcium signaling. Moreover, the
      cellular response revealed velocity dependence, that is, the cells seemed to
      respond with a higher sensitivity to a higher deformation velocity. From the
      viewpoint of cell biomechanics, these results provide us a fundamental
      understanding of the mechanosensing mechanism of osteoblast-like cells.

PMID- 16887126
TI  - Application of comprehensive two-dimensional gas chromatography with nitrogen
      selective detection for the analysis of fungicide residues in vegetable samples.
AB  - Comprehensive two-dimensional gas chromatography (GCxGC) with nitrogen-phosphorus
      detection (NPD) has been investigated for the separation and quantitation of
      fungicides in vegetable samples. The detector gas flows (H(2), N(2) and air) were
      adjusted to achieve maximum response of signal whilst minimizing peak width. The
      comparison of different column sets and selection of the temperature program were
      carried out with a mixture of nine N-containing standard fungicides, eight of
      which were chlorinated. The results from GCxGC-NPD and GCxGC with micro electron
      capture detection (muECD) were compared. External calibrations of fungicides were
      performed over a concentration range from 1 to 1,000 microgL(-1). The peak area
      calibration curves generally had regression coefficients of R(2)>0.9980, however
      for iprodione which was observed to undergo on-column degradation, an R(2) of
      0.990 was found. The limit of detection (LOD) and limit of quantitation (LOQ)
      were less than about 74 and 246 ng L(-1), respectively. The intra-day and inter
      day RSD values were measured for solutions of concentration 0.100, 0.500 and 1.50
      mg L(-1). For the 0.500 mg L(-1) solution, intra- and inter-day precision of peak
      area and peak height for most of the pesticides were about 2% and 8%,
      respectively. Excellent linearity was observed for these standards, from 0.001 to
      25.00 mg L(-1). The standard mixture peak positions were identified by using
      GCxGC with quadrupole mass spectrometry (qMS). To illustrate the potential and
      the versatility of both GCxGC-NPD and GCxGC-muECD, the method was applied to
      determination of fungicides in a vegetable extract. Decomposition of one
      fungicide standard (iprodione) during chromatography elution was readily observed
      in the two-dimensional (2D) GCxGC plot as a diagonal ridge response in the 2D
      chromatogram between the degrading compound and the decomposition product.

PMID- 16887127
TI  - Theoretical analysis of the effects of reversible dimerization in size exclusion
      chromatography.
AB  - Reversible dimer formation in size exclusion chromatography (SEC) can cause peak
      splitting, merging, tailing, and fronting. Such behavior can be predicted by the
      association rate and the dissociation rate relative to the convection rate. Slow
      association and dissociation result in separated monomer and dimer peaks. Fast
      association and slow dissociation result in one single dimer peak. Slow
      association and fast dissociation result in one single monomer peak. Intermediate
      association and dissociation result in a merged, broad peak with either fronting
      when monomers dominate or tailing when dimers dominate. A diagram based on the
      two relative rates is generated to predict general peak shape and retention
      behavior in SEC.

PMID- 16887129
TI  - Analysis of volatiles in water using headspace solid-phase microcolumn
      extraction.
AB  - A rapid solvent-free sample preparation method is presented in which volatilized
      organic substances are extracted via a solid-phase microcolumn mounted on a gas
      tight syringe by the aspiration of an appropriate volume of headspace (tens of
      millilitres) of the sample under investigation. The microcolumn with the analytes
      concentrated on an adsorbent material is then transferred to the analytical
      instrument for desorption and analysis. The instrumental set-up consists of a
      Twister desorption unit (Gerstel) mounted on an Agilent 6890 GC system equipped
      with a CIS 4 programmed temperature vaporiser injector and coupled with an
      Agilent 5973 MS system. The instrumentation is slightly modified in comparison
      with the analysis made with a twister (stir bar coated with a layer of
      polydimethylsiloxane) after stir bar sorptive extraction and, thus, its
      utilization has been extended. For volatiles in water, the method is applicable
      to the qualitative screening at the microg/l to sub-microg/l level and to the
      quantitative determination at the ng/l level.

PMID- 16887128
TI  - Histone proteins determined in a human colon cancer by high-performance liquid
      chromatography and mass spectrometry.
AB  - The application of reversed-phase high-pressure liquid chromatography under
      gradient conditions and electrospray ion trap mass spectrometry (LC-ESI-MS) to
      the analysis of global modification levels of core histones is described. The
      optimised LC-ESI-MS method was applied for the first time to the characterisation
      of histones extracted from HT29, a human colon cancer cell line. Eight histones
      (H1-1, H1-2, H2A-1, H2A-2, H2B, H3-1, H3-2, H4) were separated on a C4 stationary
      phase with complete resolution, never reached in previous HPLC-MS methods, by
      using a gradient elution with the combined presence of heptafluorobutyric acid
      and formic acid as acidic modifiers in the mobile phase. Heptafluorobutyric acid
      was found to improve selectivity, whereas the presence of formic acid decreased
      ion suppression. Histones eluted from the column were detected with an ion trap
      mass spectrometer with an electrospray source. The peak averaged mass spectra
      were reconstructed by Mag Tran 1.0 software and the mass of the various isoforms
      of histones were derived. Method validation was conducted by performing the same
      sample analysis by coupling LC-ESI to a quadrupole-time-of-flight mass
      spectrometer (Q-TOF). The number of histone forms and their mass were found to
      differ not significantly from those obtained by ion trap mass spectrometer. Also
      the relative modifications abundance within the same histone type was found
      following the same trend as the two mass analysers. This method was then applied
      to the characterisation of changes in histone modification in HT29, never
      analysed by LC-MS before, treated with histone deacetylase inhibitors such as
      valproate and sodium butyrate, also used in preclinical trials as anticancer
      drugs. In particular, both the inhibitors produced a significant increase in H4
      histone acetylated forms: 89% increase of the diacetyl dimethyl H4 form was
      observed with 1mM valproate supplementation, whereas 5 mM butyrate led to a 68%
      increase of the same form. Triacetyl monomethyl H4 (11,377 Da) and triacetyl
      dimethyl H4 (11,390 Da) were found only in cells treated with butyrate. Selective
      changes of H3 histone were detected with butyrate, in agreement with recently
      reported western blotting studies. Modifications in the H2A histone degree of
      acetylation were revealed by treatment of the cells with butyrate (H2A-1, H2A-2)
      and valproate (H2A-2). The results of the proposed methodology confirmed that
      inhibition of histone deacetylases caused histone hyperacetylation, responsible
      for decondensation and reorganization of interphase dynamic chromatin. This
      method resulted in selective and sensitive method to monitor variations in the
      acetylation and methylation state of histones after treatment of HT29 with
      inhibitors, and is therefore suitable for further application in new drug
      discovery for tumour therapy.

PMID- 16887130
TI  - Preparative separation of gambogic acid and its C-2 epimer using recycling high
      speed counter-current chromatography.
AB  - A recycling counter-current chromatographic system was first set up with a high
      speed counter-current chromatography instrument coupled with a column switching
      valve. This system was first successfully applied to the preparative separation
      of epimers, gambogic acid and epigambogic acid from Garcinia hanburyi using n
      hexane-methanol-water (5:4:1, v/v/v) as the two-phase solvent system. As a
      result, 28.2 mg gambogic acid and 18.4 mg epigambogic acid were separated from 50
      mg of mixture. Their purities were both above 97% as determined by HPLC. The
      chemical structures were then identified by their (1)H NMR and (13)C NMR spectra.

PMID- 16887131
TI  - Importance of bound water in hydration-dehydration behavior of hydroxylated
      poly(N-isopropylacrylamide).
AB  - In this study, a differential scanning calorimetric analysis was performed to
      investigate the role of water existing around the polymer chains on their
      thermoresponsive behaviors using the novel functional temperature-sensitive
      copolymer, poly(N-isopropylacrylamide-co-2-hydroxyisopropylacrylamide)
      (poly(NIPAAm-co-HIPAAm)). The HIPAAm comonomers were incorporated into the
      polymeric chains as hydrophilic parameters, and then the hydration states of
      poly(NIPAAm-co-HIPAAm) with various HIPAAm compositions were examined. Bound
      water, which is affected by the polymeric chains to some extent, was produced by
      adding the copolymers to the water, and the temperature due to the melting of the
      bound water decreased as the HIPAAm content increased. On the basis of this
      result, we considered that the interaction between the bound water and the
      polymeric chains is reinforced by the increasing HIPAAm composition. In addition,
      the cloud points of the copolymers shifted to a higher temperature, and the
      endothermic enthalpy for the phase transition decreased with increasing the
      HIPAAm content, suggesting that the number of water molecules disassociated from
      the polymeric chains decreased. Based on these results, we postulate that the
      changes in the interaction between the thermosensitive polymer and bound water
      exert a strong influence on its phase transition and/or separation, such as the
      cloud point or dehydration behavior.

PMID- 16887133
TI  - Chemical discrimination by a kinetic model of organic photooxidation in a
      heterosupramolecular assembly.
AB  - The photooxidation of range of common organic pollutants in a dye-sensitised
      photoelectrochemical cell (DS-PEC) is reported. A photoanode was prepared by the
      chemisorption of a photosensitiser, cis-bis-(2,2)-bipyridine)-(4,4'-bis
      (methyl)phosphonato-2,2'-bipyridine)ruthenium(II) dichloride
      ([Ru(bpy)2(dmpbpy]2+), to a nanoporous nanocrystalline TiO2 thin film on a
      conducting glass substrate. The photoanode was coupled to a platinum
      electroplated fluorine doped tin oxide glass substrate in a two electrode
      assembly and the cell cavity was filled with an aqueous solution of organic
      pollutants and irradiated with lambda>420 nm to give a measurable photocurrent.
      In addition to the ability of this cell to photooxidise a range of chemically
      diverse organic pollutants, the application of a kinetic model to observed
      photocurrent transients allowed the study of interfacial electron transfer
      processes. Through the mathematical fit of a five-parameter double exponential
      decay function, evidence to support numerous interfacial reactions for the
      oxidation process were identified. Rapid oxidation of species in close proximity
      to the photooxidation centre was proposed as the kinetically fast interfacial
      process with a first-order rate constant of the order 0.4 s(-1). The slower
      process was attributed to the diffusion of oxidisable species from the solution
      bulk to the surface prior to oxidation with a first-order rate constant of the
      order 0.01 s(-1). Theoretical profiling of the kinetic events supported the
      biphasic assignment of interfacial processes and indicated that non-exhaustive
      oxidation occurs for the solution concentrations examined.

PMID- 16887132
TI  - Adsorption of mixtures of nonionic sugar-based surfactants with other surfactants
      at solid/liquid interfaces I. Adsorption of n-dodecyl-beta-D-maltoside with
      anionic sodium dodecyl sulfate on alumina.
AB  - Sugar-based surfactants can be synthesized from renewable materials and are
      environmentally benign. They have some unique solution and interfacial properties
      and have potential applications in a wide variety of processes, and there is a
      need for corresponding information on their behavior at various interfaces. In
      this study, co-adsorption of nonionic sugar-based n-dodecyl-beta-D-maltoside (DM)
      and anionic sodium dodecyl sulfate (SDS) on alumina was studied as a function of
      mixing ratios and solution pHs. It is found that at solid-liquid interface,
      depending on the solid type and the solution conditions, there are various
      interactions that dictate synergy or antagonism. At pH 6 where alumina is
      positively charged, marked synergistic effects between DM and SDS were observed,
      while at pH 11 where alumina is negatively charged, SDS shows antagonistic
      adsorption effects with DM. The ratios of surfactant components on solids change
      as a function of surfactant structure and concentrations as well, indicating
      various interactions at solid/liquid interface under different conditions that
      can be utilized for many industrial processes.

PMID- 16887134
TI  - Heterogeneous Suzuki cross-coupling reactions over palladium/hydrotalcite
      catalysts.
AB  - The efficiency of various heterogeneous solids consisting of palladium supported
      on hydrotalcite as catalysts in the Suzuki cross-coupling reaction between
      bromobenzene and phenylboronic acid was studied. Based on the catalytic activity
      results, the reaction develops to an acceptable extent with 100% selectivity at
      moderate temperatures in the presence of some of the catalysts. The best results
      were provided by a catalyst consisting of an acetate-pyridine complex of Pd
      supported on hydrotalcite that gave high conversion values even after three
      reuses. The reactions conditions were very mild (a temperature of 55 degrees C
      and atmospheric pressure). In fact, the catalyst provided conversion and
      selectivity results surpassing those of existing heterogeneous phase catalysts
      and most homogeneous phase catalysts for the same purpose.

PMID- 16887135
TI  - Ligand and Charge Distribution (LCD) model for the description of fulvic acid
      adsorption to goethite.
AB  - The LCD model (Ligand and Charge Distribution) has recently been proposed to
      describe the adsorption of humic substances to oxides, in which the CD-MUSIC
      model and the NICA model for ion binding to respectively oxides and humic
      substances are integrated. In this paper, the LCD model is improved by applying
      the ADAPT model (ADsorption and AdaPTation) to calculate the equilibrium
      distribution of the humic substances based on the change of the average chemical
      state of the particles. The improved LCD model is applied to calculate the
      adsorption of fulvic acid (Strichen) to goethite, in which it is assumed that the
      carboxylic type of groups of fulvic acid can form innersphere complexes with the
      surface sites. The charge of the carboxylic groups in the innersphere complexes
      is distributed between the 0- and d-plane, whereas the charge of the other
      carboxylic and phenolic groups is located in the d-plane. The average
      distribution of the carboxylic and phenolic groups among their various chemical
      states (carboxylic groups: innersphere complex, protonated and deprotonated;
      phenolic groups: protonated and deprotonated) depends on pH, ionic strength and
      loading, and are the outcome of the model. The calculation shows that the LCD
      model can describe sufficiently the effects of pH, ionic strength and loading on
      the adsorption of fulvic acid, using one adjustable parameter (logK (S,1)). The
      model calculations indicate that the chemical complexation between fulvic acid
      and goethite is the main driving force of the adsorption, while the electrostatic
      repulsion between the particles and the surface is the major limiting factor for
      further adsorption.

PMID- 16887136
TI  - A promising system of mixed single- and double-short-tailed PEO ether phosphate
      esters: phase behavior and vesicle formation.
AB  - Acidic surfactants, single- and bi-2-methylheptanol polyethenoxy ether phosphate
      esters, H2PO3(OCH2CH2)nOCH2CH2CH2CH2CH2CH(CH3)2 (u-MHPEPE) and
      HPO3[(OCH2CH2)nOCH2CH2CH2CH2CH2CH(CH3)2]2 (d-MHPEPE), where n approximately 4,
      were synthesized. Phase behavior of u- and d-MHPEPE (u- and d-MHPEPE mixtures
      were abbreviated as MHPEPE) mixtures in aqueous solutions and vesicle formation
      were determined. Surface tension measurements showed that u-MHPEPE and MHPEPE
      have low surface tensions at critical micelle concentrations. gamma(cmc)=29.0
      mNm(-1) and cmc=16.0 mmolL(-1) for u-MHPEPE, MHPEPE has two transition points
      suggesting the mixtures of u- and d-MHPEPE with gamma(cmc1)=30.5 mNm(-1) and
      cmc1=4.0 mmolL(-1), and gamma(cmc2)=27.3 mNm(-1) and cmc2=42.0 mmolL(-1). These
      values, specific gamma(cmc), are much lower than those of traditionally cationic
      or anionic surfactants such as cetyltrimethylammonium bromide (CTAB,
      gamma(cmc)=37.1 mNm(-1) at cmc=0.92 mmolL(-1)) and sodium dodecyl sulfate (SDS,
      gamma(cmc)=39.0 mNm(-1) at cmc=8.1 mmolL(-1)). Rich phase behavior was observed
      with increasing MHPEPE concentration, an isotropic L(1)-phase (micelle solution),
      an unstable emulsion-region (with time, the samples separate into two-phase), a
      transparently bluish and birefringent Lalpha-phase up to 200 mmol L(-1) with
      unilamellar and multilamellar vesicles. These unilamellar and multilamellar
      vesicles were demonstrated by using staining transmission electron microscopy
      (staining-TEM), which were compared to freeze-fracture TEM (FF-TEM). The vesicle
      phase is stable for at least 1 year. Vesicle formation possibly could be
      explained in harmonization of the hydrophobic force of acidic surfactant tails,
      the hydrogen bonding (H-bonding) and the electrostatic interaction among polar
      headgroups of PEO ether phosphate ester. Phase transition from the flow
      birefringent unilamellar vesicles induced by addition of HCl, NaCl, NaOH, and
      increasing temperature has been observed. Surprisingly, for u-MHPEPE or d-MHPEPE
      in water, we just observed L1-phase (micelle solution) with increasing u-MHPEPE
      or d-MHPEPE concentration.

PMID- 16887137
TI  - Are the mixtures of homologous surfactants ideal?
AB  - The interaction between homologous surfactants in mixed micelles was studied by
      the Regular Solution Theory of mixed micelles. The interaction is independent of
      the nature of the polar head groups and attractive and the interaction parameter
      betaM depends linearly on the difference in chain length DeltanC. The interaction
      becomes ideal at DeltanC=0.75+/-0.06. Above DeltanC approximately 5, the
      dependence remains linear but the slope increased 2.7 times. The phenomenon is
      explained as the effect of the reduction of the hydrocarbon/water micelle
      interface and a better packing of the chains in the micelle core, caused by the
      inclusion of a shorter homologous surfactants. This reduction can be more
      effective when DeltanC>or=5.

PMID- 16887138
TI  - Colloidal stability of pluronic F68-coated PLGA nanoparticles: a variety of
      stabilisation mechanisms.
AB  - Poloxamers are a family of polypropylene oxide (PPO) and polyethylene oxide (PEO)
      tri-block copolymers that are usually employed in the micro- and nanoparticulate
      engineering for drug delivery systems. The aim of this work is to study the
      electrophoretic mobility (mu(e)) and colloidal stability of complexes formed by
      adsorbing a poloxamer (Pluronic F68) onto poly(d,l-lactic-co-glycolic acid)
      (PLGA) nanoparticles. A variety of stabilisation mechanisms have been observed
      for the Pluronic-coated PLGA nanoparticles, where DLVO interactions, solvent
      polymer segment interactions and hydration forces play different roles as a
      function of the adsorbed amount of Pluronic. In addition, the mu(e) and stability
      data of these complexes have been compared to those obtained previously using a
      PLGA-Pluronic F68 blend formulation. As both the mu(e) and the stability data are
      identical between the two systems, a phase separation of both components in the
      PLGA-Pluronic blend formulation is suggested, being the PLGA located in the core
      of the particles and the Pluronic in an adsorbed shell.

PMID- 16887140
TI  - Deficient implicit phonological representations in children with dyslexia.
AB  - This study tested the segmentation hypothesis of dyslexia by measuring implicit
      phonological representations in reading-disabled 11- to 13-year-olds. Implicit
      measures included lexical gating, priming, and syllable similarity tasks designed
      to reduce metalinguistic demands. Children with dyslexia performed consistently
      worse than CA and RA controls when more segmental representations were required
      across all three tasks. Implicit phonological representations were correlated
      with measures of speech perception, phoneme awareness, and phonological short
      term memory, but not rapid automatized naming, and accounted for unique variance
      in predicting reading ability. Results provide strong support for less mature
      implicit phonological representations in children with dyslexia.

PMID- 16887139
TI  - Cortical interactions underlying the production of speech sounds.
AB  - Speech production involves the integration of auditory, somatosensory, and motor
      information in the brain. This article describes a model of speech motor control
      in which a feedforward control system, involving premotor and primary motor
      cortex and the cerebellum, works in concert with auditory and somatosensory
      feedback control systems that involve both sensory and motor cortical areas. New
      speech sounds are learned by first storing an auditory target for the sound, then
      using the auditory feedback control system to control production of the sound in
      early repetitions. Repeated production of the sound leads to tuning of
      feedforward commands which eventually supplant the feedback-based control
      signals. Although parts of the model remain speculative, it accounts for a wide
      range of kinematic, acoustic, and neuroimaging data collected during speech
      production and provides a framework for investigating communication disorders
      that involve malfunction of the cerebral cortex and interconnected subcortical
      structures. LEARNING OUTCOMES: Readers will be able to: (1) describe several
      types of learning that occur in the sensory-motor system during babbling and
      early speech, (2) identify three neural control subsystems involved in speech
      production, (3) identify regions of the brain involved in monitoring auditory and
      somatosensory feedback during speech production, and (4) identify regions of the
      brain involved in feedforward control of speech.

PMID- 16887141
TI  - Efficient and reproducible large-scale isolation of human CD4+ CD25+ regulatory T
      cells with potent suppressor activity.
AB  - CD4+ CD25+ regulatory T cells have been the subject of intense investigation and
      have been shown to modulate immune responses in the settings of autoimmunity,
      cancer and transplantation. The assessment and optimization of purification
      schemes for specific cellular subtypes such as CD4+ CD25+ regulatory T cells is a
      critical consideration in developing cell-based therapies in the clinical
      setting. In the following studies, different strategies for magnetic isolation
      are compared and the parameters which affect the overall potency of purified
      human CD4+ CD25+ regulatory T cells are discussed. The data demonstrate that
      large-scale magnetic isolation can be used to efficiently and reproducibly purify
      human CD4+ CD25+ regulatory T cells capable of modulating alloreactive T cell
      responses. The ability to rapidly purify the desired cells from peripheral blood
      suggests that magnetic isolation may be a suitable alternative to cell sorting
      for clinical settings, where large numbers of CD4+ CD25+ regulatory T cells may
      be necessary.

PMID- 16887142
TI  - A critical developmental role for tgfbr2 in myogenic cell lineages is revealed in
      mice expressing SM22-Cre, not SMMHC-Cre.
AB  - Smooth muscle cell (SMC)-specific deletion of transforming growth factor beta
      (TGF-beta) signaling would help elucidate the mechanisms through which TGF-beta
      signaling contributes to vascular development and disease. We attempted to
      generate mice with SMC-specific deletion of TGF-beta signaling by mating mice
      with a conditional ("floxed") allele for the type II TGF-beta receptor
      (tgfbr2flox) to mice with SMC-targeted expression of Cre recombinase. We bred
      male mice transgenic for smooth muscle myosin heavy chain (SMMHC)-Cre with
      females carrying tgfbr2flox. Surprisingly, SMMHC-Cre mice recombined tgfbr2flox
      at low levels in SMC and at high levels in the testis. Recombination of
      tgfbr2flox in testis correlated with high-level expression of SMMHC-Cre in testis
      and germline transmission of tgfbr2null. In contrast, mice expressing Cre from a
      SM22alpha promoter (SM22-Cre) efficiently recombined tgfbr2flox in vascular and
      visceral SMC and the heart, but not in testis. Use of the R26R reporter allele
      confirmed that Cre-mediated recombination in vascular SMC was inefficient for
      SMMHC-Cre mice and highly efficient for SM22-Cre mice. Breedings that introduced
      the SM22-Cre allele into tgfbr2flox/flox zygotes in order to generate adult mice
      that are hemizygous for SM22-Cre and homozygous for tgfbr2flox- and would have
      conversion of tgfbr2flox/flox to tgfbr2null/null in SMC-produced no live SM22-Cre
      : tgfbr2flox/flox pups (P<0.001). We conclude: (1) "SMC-targeted" Cre lines vary
      significantly in specificity and efficiency of Cre expression; (2) TGF-beta
      signaling in the subset of cells that express SM22alpha is required for normal
      development; (3) generation of adult mice with absent TGF-beta signaling in SMC
      remains a challenge.

PMID- 16887143
TI  - Inhibition of RecBCD enzyme by antineoplastic DNA alkylating agents.
AB  - To understand how bulky adducts might perturb DNA helicase function, three
      distinct DNA-binding agents were used to determine the effects of DNA alkylation
      on a DNA helicase. Adozelesin, ecteinascidin 743 (Et743) and hedamycin each
      possess unique structures and sequence selectivity. They bind to double-stranded
      DNA and alkylate one strand of the duplex in cis, adding adducts that alter the
      structure of DNA significantly. The results show that Et743 was the most potent
      inhibitor of DNA unwinding, followed by adozelesin and hedamycin. Et743
      significantly inhibited unwinding, enhanced degradation of DNA, and completely
      eliminated the ability of the translocating RecBCD enzyme to recognize and
      respond to the recombination hotspot chi. Unwinding of adozelesin-modified DNA
      was accompanied by the appearance of unwinding intermediates, consistent with
      enzyme entrapment or stalling. Further, adozelesin also induced "apparent" chi
      fragment formation. The combination of enzyme sequestering and pseudo-chi
      modification of RecBCD, results in biphasic time-courses of DNA unwinding.
      Hedamycin also reduced RecBCD activity, albeit at increased concentrations of
      drug relative to either adozelesin or Et743. Remarkably, the hedamycin
      modification resulted in constitutive activation of the bottom-strand nuclease
      activity of the enzyme, while leaving the ability of the translocating enzyme to
      recognize and respond to chi largely intact. Finally, the results show that DNA
      alkylation does not significantly perturb the allosteric interaction that
      activates the enzyme for ATP hydrolysis, as the efficiency of ATP utilization for
      DNA unwinding is affected only marginally. These results taken together present a
      unique response of RecBCD enzyme to bulky DNA adducts. We correlate these effects
      with the recently determined crystal structure of the RecBCD holoenzyme bound to
      DNA.

PMID- 16887145
TI  - Kinetics of ATP-stimulated nuclease activity of the Escherichia coli RecBCD
      enzyme.
AB  - The RecBCD enzyme is an ATP-dependent nuclease on both single-stranded and double
      stranded DNA substrates. We have investigated the kinetics of the RecBCD
      catalyzed reaction with small, single-stranded oligodeoxyribonucleotide
      substrates under single-turnover conditions using rapid-quench flow techniques.
      RecBCD-DNA complexes were allowed to form in pre-incubation mixtures. The
      nuclease reactions were initiated by mixing with ATP. The reaction time-courses
      were fit to several possible reaction mechanisms and quantitative estimates were
      obtained for rate constants for individual reaction steps. The relative rates of
      forward reaction versus dissociation from the DNA, and the fact that inclusion of
      excess non-radiolabeled single-stranded DNA to trap free RecBCD has no effect on
      the nuclease reaction, indicates that the reaction is processive. The reaction
      products show that the reaction begins near the 3'-end of the [5'-32P]DNA
      substrates and the major cleavage sites are two to four phosphodiester bonds
      apart. The product distribution is unchanged as the ATP concentration varies from
      10 microM to 100 microM ATP, while the overall reaction rate varies by about
      tenfold. These observations suggest that DNA cleavage is tightly coordinated with
      movement of the enzyme along the DNA. The reaction time-courses at low
      concentrations of ATP (10 microM and 25 microM) have a significant lag before
      cleavage products appear. We propose that the lag represents ATP-dependent
      movement of the DNA from an initial binding site in the helicase domain of the
      RecB subunit to the nuclease active site in a separate domain of RecB. The extent
      of reaction of the substrate is limited (approximately 50%) under all conditions.
      This may indicate the formation of a non-productive RecBCD-DNA complex that does
      not dissociate in the 1-2 s time-scale of our experiments.

PMID- 16887144
TI  - The myosin filament superlattice in the flight muscles of flies: A-band lattice
      optimisation for stretch-activation?
AB  - Low-angle X-ray diffraction patterns from relaxed fruitfly (Drosophila) flight
      muscle recorded on the BioCat beamline at the Argonne Advanced Photon Source
      (APS) show many features similar to such patterns from the "classic" insect
      flight muscle in Lethocerus, the giant water bug, but there is a
      characteristically different pattern of sampling of the myosin filament layer
      lines, which indicates the presence of a superlattice of myosin filaments in the
      Drosophila A-band. We show from analysis of the structure factor for this lattice
      that the sampling pattern is exactly as expected if adjacent four-stranded myosin
      filaments, of repeat 116 nm, are axially shifted in the hexagonal A-band lattice
      by one-third of the 14.5 nm axial spacing between crowns of myosin heads. In
      addition, electron micrographs of Drosophila and other flies (e.g. the house fly
      (Musca) and the flesh fly (Sarcophaga)) combined with image processing confirm
      that the same A-band superlattice occurs in all of these flies; it may be a
      general property of the Diptera. The different A-band organisation in flies
      compared with Lethocerus, which operates at a much lower wing beat frequency
      (approximately 30 Hz) and requires a warm-up period, may be a way of optimising
      the myosin and actin filament geometry needed both for stretch activation at the
      higher wing beat frequencies (50 Hz to 1000 Hz) of flies and their need for a
      rapid escape response.

PMID- 16887146
TI  - Genetic structure of the dopamine receptor D4 gene (DRD4) and lack of association
      with schizophrenia in Japanese patients.
AB  - In order to investigate the contribution of genetic variation in the human
      dopamine receptor D4 gene (DRD4) to the risk of developing schizophrenia, we
      carried out a genetic analysis of 27 polymorphisms in 216 schizophrenic patients
      and 243 healthy controls from the Kyushu region of Japan. Twenty-two single
      nucleotide polymorphisms (SNPs) and five insertion/deletion polymorphisms were
      analyzed in this study, including four novel SNPs and a novel mononucleotide
      repeat. Linkage disequilibrium (LD) and haplotype analyses reveal weak LD across
      the DRD4 gene. In univariate analysis female individuals with allele -521C had a
      higher risk for schizophrenia. However, this finding was not significant after
      correction for multiple hypothesis testing. No other polymorphisms or haplotypes
      differed between schizophrenic patients and controls. Likewise, multivariate
      analyses did not reveal any statistically significant associations.

PMID- 16887148
TI  - Anxiety disorders: prevalence, comorbidity and outcomes.

PMID- 16887147
TI  - The relationship between psychological dimensions of depressive symptoms and
      cognitive functioning in the elderly - the MEMO-Study.
AB  - Aim of this study was to examine the association of symptom dimensions of
      depressive symptoms and cognitive functioning in the elderly. In a population
      based study with 365 participants 65-83 years of age, dimensions of depressive
      symptoms were assessed with the four subscales of the CES-D-score and
      standardized cognitive tests assessing attention, memory, cognitive speed, and
      motor speed were performed. Compared to men, women scored significantly higher on
      the subscales for depressed affect and somatic complaints. Older participants had
      a significantly higher score for interpersonal difficulties. Participants with
      lower education had higher scores on all four psychological dimensions of
      depressive symptoms than those with high education (only significant for
      depressive affect). Individuals scoring high on CES-D subscales for depressive
      affect and somatic complaints had statistically significant (after Bonferroni
      adjustment) lower scores in attention and motor function in multivariate
      analyses. No significant associations between the symptom dimensions of positive
      affect and interpersonal difficulties with any of the cognitive tests were found
      in univariate and multivariate analyses (after Bonferroni adjustment). Our
      findings suggest specific patterns in the relationships between symptom
      dimensions of depressive symptoms and cognitive dysfunction in the general
      elderly population. This novel approach might be useful in addressing the
      heterogeneity of cognitive impairment in depression and in predicting cognitive
      outcome in depression.

PMID- 16887149
TI  - Expression of CCR7 and its ligands CCL19/CCL21 in muscles of polymyositis.
AB  - Polymyositis is an autoimmune disorder in which autoaggressive CD8(+) T cells are
      important in the pathogenesis. However, the mechanisms underlying sustained
      recruitment of these cells in the muscle tissue are still unknown. CCR7 and its
      ligands CCL19 and CCL21 are a chemokine system related to mononuclear cell
      migration and antigen presentation, and are suggested to play a key role in
      several autoimmune disorders. We investigated the expression of CCR7, CCL19 and
      CCL21 in frozen muscles of polymyositis. In immunohistochemistry, CCR7 was
      expressed mainly on mononuclear cells that infiltrated in the endomysium of
      polymyositis. 34.8+/-9.4% of endomysial mononuclear cells expressed CCR7. By
      double immunostaining, about 60% of endomysial CD8(+) T cells that surrounded the
      nonnecrotic muscle fibers coexpressed CCR7. Because most endomysial CD8(+) T
      cells expressed CD45RO, these were regarded as CD45RO(+)CCR7(+)CD8(+) T cells. On
      the other hand, CCL19 was expressed mainly on muscle fibers in proximity to
      CCR7(+) mononuclear cells, on the endothelium of the vessels and some mononuclear
      cells. CCL21 immunoreactivities were found on small numbers of mononuclear cells.
      In some cases, CCL21 immunoreactivities were also found on muscle fibers and the
      endothelium of vessels. In RT-PCR analysis, transcripts of CCR7 and CCL21 were
      detected in all the polymyositis muscles examined and that of CCL19 was detected
      in five out of seven polymyositis muscles. The CCL19,CCL21/CCR7 chemokine system
      is expressed in inflamed muscles of polymyositis and may be involved in the
      pathomechanism of polymyositis.

PMID- 16887150
TI  - How canalization can make loops: a new model of reticulated leaf vascular pattern
      formation.
AB  - Formation of the vascular system in plant leaves can be explained by the
      canalization hypothesis which states that veins are formed in an initially
      homogeneous field by a self-organizing process between the plant hormone auxin
      and auxin carrier proteins. Previous models of canalization can generate vein
      patterns with branching but fail to generate vein patterns with closed loops.
      However, closed vein loops are commonly observed in plant leaves and are
      important in making them robust to herbivore attacks and physical damage. Here we
      propose a new model which generates a vein system with closed loops. We postulate
      that the "flux bifurcator" level is enhanced in cells with a high auxin flux and
      that it causes reallocation of auxin carriers toward neighbouring cells also
      having a high bifurcator level. This causes the auxin flux to bifurcate, allowing
      vein tips to attach to other veins creating vein loops. We explore several
      alternative functional forms for the flux bifurcator affecting the reallocation
      of efflux carriers and examine parameter dependence of the resulting vein
      pattern.

PMID- 16887151
TI  - Partnership dynamics and strain competition.
AB  - Models of epidemic spread that include partnership dynamics within the host
      population have demonstrated that finite length partnerships can limit the spread
      of pathogens. Here the influence of partnerships on strain competition is
      investigated. A simple epidemic and partnership formation model is used to
      demonstrate that, in contrast to standard epidemiological models, the constraint
      introduced by partnerships can influence the success of pathogen strains. When
      partnership turnover is slow, strains must have a long infectious period in order
      to persist, a requirement of much less importance when partnership turnover is
      rapid. By introducing a trade-off between transmission rate and infectious period
      it is shown that populations with different behaviours can favour different
      strains. Implications for control measures based on behavioural modifications are
      discussed, with such measures perhaps leading to the emergence of new strains.

PMID- 16887152
TI  - Age, rank, and personality effects on the cortisol sedation stress response in
      young chimpanzees.
AB  - Primates and other mammals exhibit a glucocorticoid response to somatic and
      psychosocial stressors. The pattern and degree of response varies both within and
      between species, but the factors affecting within-species variability have rarely
      been considered. Here we describe the 90-min serum cortisol response of 14
      juvenile and adolescent chimpanzees to the stress of sedation with ketamine
      hydrochloride. We show age differences in both baseline cortisol and time of peak
      cortisol, with younger individuals (ages 4-5 years) showing higher baseline
      levels and an earlier peak response than older individuals (ages 8-9 years).
      However, we found no sex or rank-related differences in any of the sedation
      measures: baseline cortisol, cortisol peak time, peak cortisol level, or cortisol
      change from baseline. We also examined the relationship between these sedation
      stress measures and behavioral style score, and found that individuals scoring
      high in the "mellow" behavioral style component showed a greater stress response
      than individuals scoring lower in this component. Future studies should consider
      the role of individual differences in age and personality in the cortisol
      response to stress.

PMID- 16887154
TI  - Induction of anxiety-like behavior in mice during the initial stages of infection
      with the agent of murine colonic hyperplasia Citrobacter rodentium.
AB  - Symptoms of anxiety frequently occur concomitant to the development and
      persistence of inflammatory bowel disease (IBD) in patients. In the present
      study, we utilized an animal model of IBD, infection with Citrobacter rodentium,
      to determine whether the infection per se can drive anxiety-like behavior. Nine
      week-old CF-1 male mice were challenged orally with either saline or C.
      rodentium. Early in the infective process (7-8 h later), mice were tested on a
      hole-board open field apparatus for anxiety-like behavior measurement.
      Immediately following behavioral testing, plasma samples were obtained for immune
      cytokine analysis and colons were excised for histological analysis. In
      additional animals, vagal ganglia were removed and processed for c-Fos protein
      detection. Challenge with C. rodentium significantly increased anxiety-like
      behavior as evidenced by avoidance of the center area and increased risk
      assessment behavior. Plasma levels of the cytokines IFN-gamma, TNF-alpha and IL
      12 were not different. However vagal sensory ganglia from C. rodentium-treated
      animals evinced significantly more c-Fos protein-positive neurons, consistent
      with vagal afferent transmission of C. rodentium-related signals from gut to
      brain. Histological examination of the colon indicated a lack of overt
      inflammation at the 8 h post-challenge time point, indicating that the
      differences in behavior were unlikely to follow from inflammation-related stress.
      The results of the present study demonstrate that infection with C. rodentium can
      induce anxiety-like symptoms that are likely mediated via vagal sensory neurons.

PMID- 16887153
TI  - Hindbrain catecholamine neurons control multiple glucoregulatory responses.
AB  - Reduced brain glucose availability evokes an integrated constellation of
      responses that protect and restore the brain's glucose supply. These include
      increased food intake, adrenal medullary secretion, corticosterone secretion and
      suppression of estrous cycles. Our research has focused on mechanisms and neural
      circuitry underlying these systemic glucoregulatory responses. Using
      microinjection techniques, we found that localized glucoprivation of hindbrain
      but not hypothalamic sites, elicited key glucoregulatory responses, indicating
      that glucoreceptor cells controlling these responses are located in the
      hindbrain. Selective destruction of hindbrain catecholamine neurons using the
      retrogradely transported immunotoxin, anti-dopamine beta-hydroxylase conjugated
      to saporin (DSAP), revealed that spinally-projecting epinephrine (E) or
      norepinephrine (NE) neurons are required for the adrenal medullary response to
      glucoprivation, while E/NE neurons with hypothalamic projections are required for
      feeding, corticosterone and reproductive responses. We also found that E/NE
      neurons are required for both consummatory and appetitive phases of glucoprivic
      feeding, suggesting that multilevel collateral projections of these neurons
      coordinate various components of the behavioral response. Epinephrine or NE
      neurons co-expressing neuropeptide Y (NPY) may be the neuronal phenotype required
      for glucoprivic feeding: they increase NPY mRNA expression in response to
      glucoprivation and are nearly eliminated by DSAP injections that abolish
      glucoprivic feeding. In contrast, lesion of arcuate nucleus NPY neurons, using
      the toxin, NPY-saporin, does not impair glucoprivic feeding or hyperglycemic
      responses. Thus, hindbrain E/NE neurons orchestrate multiple concurrent
      glucoregulatory responses. Specific catecholamine phenotypes may mediate the
      individual components of the overall response. Glucoreceptive control of these
      neurons resides within the hindbrain.

PMID- 16887155
TI  - The effect of repeated exposure to fruit drinks on intake, pleasantness and
      boredom in young and elderly adults.
AB  - The effect of a repeated monotonous exposure on ad libitum intake, pleasantness
      and boredom in elderly people in a real life situation is unclear. We therefore
      investigated the effects of repeated exposure to ad libitum intake of three
      orange-based drinks on boredom and acceptance in young and elderly people. Young
      (n=32) and elderly women (n=36) participated in a randomized within subjects
      cross over trial with three intervention periods of 12 days each followed by a 2
      day wash out period. During each intervention period, the participants received 1
      L of one type of drink per day. The three drinks varied in sweetness intensity.
      Intake was measured by weighing the returned packets and pleasantness, boredom
      and sweetness were rated on a 10-point scale. For the young women, mean
      consumption of the three drinks (p<0.01) and pleasantness decreased (p<0.01) and
      boredom increased (p<0.001). For the elderly women, consumption increased
      (p=0.03) whereas pleasantness (p=0.34) and boredom (p=0.40) were stable. In the
      young women, the orange peach drink which had the highest sugar content
      contributed the most to the effect of the repeated exposure. The consumption and
      pleasantness ratings for this drink decreased (r=-1.05, p=0.01 and r=-0.07,
      p=0.007, respectively) and boredom increased (r=0.12, p<0.001). In conclusion,
      elderly women experienced no increased boredom whereas young women did.

PMID- 16887156
TI  - Deterrent activity of plant lectins on cowpea weevil Callosobruchus maculatus
      (F.) oviposition.
AB  - A set of 14 plant lectins was screened in a binary choice bioassay for inhibitory
      activity on cowpea weevil Callosobruchus maculatus (F.) oviposition. Coating of
      chickpea seeds (Cicer arietinum L.) with a 0.05% (w/v) solution of plant lectins
      caused a significant reduction in egg laying. Control experiments with heat
      inactivated lectin and BSA indicated that the observed deterrent effects are
      specific and require carbohydrate-binding activity. However, no clear correlation
      could be established between deterrent activity and sugar-binding
      specificity/molecular structure of the lectins. Increasing the insect density
      reduced the inhibitory effect of the lectins confirming that female insects are
      capable of adjusting their oviposition rates as a function of host availability.

PMID- 16887157
TI  - Comparing the use of an accident and emergency department by children from two
      Local Authority Gypsy sites with that of their neighbours.

PMID- 16887158
TI  - Effect of intramammary infusion of bacterial lipopolysaccharide on experimentally
      induced Staphylococcus aureus intramammary infection.
AB  - Mastitis due to Staphylococcus aureus is a significant problem in the dairy
      industry and is refractory to antibiotic treatment and/or vaccine prevention.
      Relative to other mastitis-causing pathogens, S. aureus elicits a diminutive host
      inflammatory response during intramammary infection. To determine whether
      induction of a heightened inflammatory response could influence outcome of
      infection, the highly pro-inflammatory molecule bacterial lipopolysaccharide
      (LPS) was infused into udder quarters experimentally infected with S. aureus.
      Relative to S. aureus-infected udder quarters receiving saline, quarters infused
      with LPS demonstrated a heightened inflammatory response as demonstrated by the
      induction of TNF-alpha and higher milk somatic cell counts and albumin levels.
      Although there was no overall effect on bacterial clearance, a trend toward
      reduced bacterial numbers during the immediate pro-inflammatory response
      following LPS infusion was observed suggesting that this novel approach to
      treating S. aureus intramammary infection may warrant further investigation.

PMID- 16887159
TI  - Antibodies against Lutzomyia longipalpis saliva in the fox Cerdocyon thous and
      the sylvatic cycle of Leishmania chagasi.
AB  - Sera of 11 wild Cerdocyon thous foxes from an endemic area for American visceral
      leishmaniasis were tested for the presence of antibodies against salivary gland
      homogenates (SGH) of Lutzomyia longipalpis. All foxes had higher levels of anti
      Lu. longipalpis SGH antibodies than foxes from non-endemic areas, suggesting
      contact between foxes and the vector of visceral leishmaniasis. Sera of humans
      and dogs living in the same area were also tested for reactivity against Lu.
      longipalpis SGHs and had a lower proportion of reactivity than foxes. Antibodies
      against Leishmania chagasi were not detected in any of the foxes, but three foxes
      showed the presence of parasites in the bone marrow by direct examination, PCR or
      by infecting the vector. Both humans and dogs had higher levels of anti-Le.
      chagasi IgG antibodies than C. thous. The finding of an antibody response against
      saliva of Lu. longipalpis among C. thous together with the broad distribution of
      the vector in resting areas of infected foxes suggests that the natural foci of
      transmission of Le. chagasi exists independently of the transmission among dogs
      and humans.

PMID- 16887160
TI  - Non-equilibrium theory of the allele frequency spectrum.
AB  - A forward diffusion equation describing the evolution of the allele frequency
      spectrum is presented. The influx of mutations is accounted for by imposing a
      suitable boundary condition. For a Wright-Fisher diffusion with or without
      selection and varying population size, the boundary condition is lim(x downward
      arrow0)xf(x,t)=thetarho(t), where f(.,t) is the frequency spectrum of derived
      alleles at independent loci at time t and rho(t) is the relative population size
      at time t. When population size and selection intensity are independent of time,
      the forward equation is equivalent to the backwards diffusion usually used to
      derive the frequency spectrum, but this approach allows computation of the time
      dependence of the spectrum both before an equilibrium is attained and when
      population size and selection intensity vary with time. From the diffusion
      equation, a set of ordinary differential equations for the moments of f(.,t) is
      derived and the expected spectrum of a finite sample is expressed in terms of
      those moments. The use of the forward equation is illustrated by considering
      neutral and selected alleles in a highly simplified model of human history. For
      example, it is shown that approximately 30% of the expected total heterozygosity
      of neutral loci is attributable to mutations that arose since the onset of
      population growth in roughly the last 150,000 years.

PMID- 16887161
TI  - On dentinal innervation.

PMID- 16887162
TI  - Accumulation and depuration profiles of PSP toxins in the short-necked clam Tapes
      japonica fed with the toxic dinoflagellate Alexandrium catenella.
AB  - A toxic dinoflagellate responsible for paralytic shellfish poisoning (PSP),
      Alexandrium catenella (Ac) was fed to the short-necked clam Tapes japonica, and
      the accumulation and depuration profiles of PSP toxins were investigated by means
      of high-performance liquid chromatography with postcolumn fluorescence
      derivatization (HPLC-FLD). The short-necked clams ingested more than 99% of the
      Ac cells (4 x 10(7)cells) supplied once at the beginning of experiment, and
      accumulated a maximal amount of toxin (185 nmol/10 clams) after 12h. The rate of
      toxin accumulation at that time was 23%, which rapidly decreased thereafter.
      Composition of the PSP toxin accumulated in the clams obviously different from
      that of Ac even 0.5h after the cell supply, the proportion of C1+2 being much
      higher than in Ac, although the reason remains to be elucidated. In contrast, a
      higher ratio of gonyautoxin (GTX)1+4 than in Ac was detected in the toxin
      profiles of clam excrements. The variation in toxin composition derived
      presumably from the transformation of toxin analogues in clams was observed from
      0.5h, such as reversal of the ratio of C1 to C2, and appearance of carbamate
      (saxitoxin (STX), neoSTX and GTX2, 3) and decarbamoyl (dc) derivatives (dcSTX and
      dcGTX2, 3), which were undetectable in Ac cells. The total amount of toxin
      distributed over Ac cells, clams and their excrements gradually declined, and
      only 1% of supplied toxin was detected at the end of experiment.

PMID- 16887164
TI  - Quantitative analysis of a virulent bacteriophage transcription strategy.
AB  - An increasingly large number of bacteriophage genomes are being sequenced each
      year. What is an efficient experimental and computational procedure to analyze
      transcription strategies of newly sequenced novel bacteriophages? We address this
      issue using an example of bacteriophage Xp10, which infects rice pathogen
      Xanthomonas oryzae. This phage is particularly challenging for analysis, since
      part of its genome is jointly transcribed by two (host and viral) RNA
      polymerases. To understand the roles played by the two RNA polymerases, we
      developed a novel method of data analysis which combines quantitative analysis of
      Xp10 global gene expression data and kinetic modeling of the infection process.
      To generalize our approach, we discuss how our method can be applied to other
      systems and argue that genomic array experiments combined with the methods of
      data analysis that we present provide an efficient way to analyze gene expression
      strategies of novel bacteriophages.

PMID- 16887163
TI  - Effects of human TRIM5alpha polymorphisms on antiretroviral function and
      susceptibility to human immunodeficiency virus infection.
AB  - TRIM5alpha acts on several retroviruses, including human immunodeficiency virus
      (HIV-1), to restrict cross-species transmission. Using natural history cohorts
      and tissue culture systems, we examined the effect of polymorphism in human
      TRIM5alpha on HIV-1 infection. In African Americans, the frequencies of two non
      coding SNP variant alleles in exon 1 and intron 1 of TRIM5 were elevated in HIV-1
      infected persons compared with uninfected subjects. By contrast, the frequency of
      the variant allele encoding TRIM5alpha 136Q was relatively elevated in uninfected
      individuals, suggesting a possible protective effect. TRIM5alpha 136Q protein
      exhibited slightly better anti-HIV-1 activity in tissue culture than the
      TRIM5alpha R136 protein. The 43Y variant of TRIM5alpha was less efficient than
      the H43 variant at restricting HIV-1 and murine leukemia virus infections in
      cultured cells. The ancestral TRIM5 haplotype specifying no observed variant
      alleles appeared to be protective against infection, and the corresponding wild
      type protein partially restricted HIV-1 replication in vitro. A single logistic
      regression model with a permutation test indicated the global corrected P value
      of <0.05 for both SNPs and haplotypes. Thus, polymorphism in human TRIM5 may
      influence susceptibility to HIV-1 infection, a possibility that merits additional
      evaluation in independent cohorts.

PMID- 16887165
TI  - DNA sequence-directed assembly of two peptide bioconjugates.
AB  - Peptide bioconjugates combine the molecular recognition features of the
      polypeptide from a DNA-binding protein and the DNA-sensitive fluorescence of an
      intercalating dye. Here, DNA template-directed assembly of two bioconjugate
      probes was examined by steady-state fluorescence resonance energy transfer and
      time-resolved single photon counting. The Forster critical distance was
      determined to be approximately 26 A for the oxazole yellow and thiazole orange
      donor-acceptor pair. The efficiency of energy transfer for two bioconjugates was
      a function of the number of intervening base pairs between two DNA cognate sites.
      These probes were sufficiently sensitive to detect sequence dependent curvature
      and polypeptide induced bending of the DNA. Molecular probes capable of examining
      spatial aspects of protein complexes at promoter sites could yield important
      information about the early events in transcription initiation.

PMID- 16887166
TI  - Regression method of the hydrophobicity ruler approach for determining
      octanol/water partition coefficients of very hydrophobic compounds.
AB  - A regression method was developed for the hydrophobicity ruler approach, which is
      an indirect method for determining the octanol/water partition coefficients of
      very hydrophobic compounds. Two constants introduced into the mathematical model
      were obtained by regression of the absorption data sampled before the partition
      equilibrium. A water miscible organic solvent was used to increase the solubility
      of the very hydrophobic compounds in the aqueous solution so that the
      hydrophobicity scale was reduced and the equilibration was accelerated.
      Polydimethylsiloxane/methanol aqueous solution and a series of 21 polychlorinated
      biphenyls (PCBs) were used to demonstrate the regression method. The PCB
      compounds with known experimental logK(o/w) values served as reference compounds,
      while the PCB compounds without known logK(o/w) values were determined. The
      distribution coefficients (logK(p/s)), uptake and elimination rate constants were
      obtained from the two regression constants for each compound (reference or
      unknown). The correlation of the logK(p/s) values of the reference PCB compounds
      with their logK(o/w) values was linear (logK(o/w)=2.69logK(p/s)+0.76, R(2)=0.97).
      The logK(o/w) values were compared with literature values and suggested that some
      values from the literature far off the calibration line could be inaccurate. The
      critical experimental factors, the merits of the regression method were
      discussed.

PMID- 16887167
TI  - The use of a sequential leaching procedure for assessing the heavy metal
      leachability in lime waste from the lime kiln at a caustizicing process of a pulp
      mill.
AB  - A five-stage sequential leaching procedure was used to fractionate 13 heavy
      metals (Cd, Cu, Pb, Cr, Zn, Fe, Mn, Al, Ni, Co, As, V, Ba) and sulphur (S) in
      lime waste from the lime kiln at the causticizing plant of Stora Enso Oyj
      Veitsiluoto Pulp Mills at Kemi, Northern Finland, into the following fractions:
      (1) water-soluble fraction (H(2)O), (2) exchangeable fraction (CH(3)COOH), (3)
      easily reduced fraction (HONH(3)Cl), (4) oxidizable fraction
      (H(2)O(2)+CH(3)COONH(4)), and (5) residual fraction (HF+HNO(3)+HCl). Although
      metals were leachable in all fractions, the highest concentrations for most of
      the metals were observed in the residual fraction (stage 5). It was also notable
      that the total heavy metal concentrations in lime waste did not exceed the
      maximal allowable heavy metal concentrations for soil conditioner agents set by
      the ministry of the Agricultural and Forestry in Finland. The heavy metals
      concentrations in lime waste were also lower than the maximal allowable heavy
      metals concentrations of the European Union Directive 86/278/EEC on the
      protection of environment, and in particular of the soil, when sewage sludge is
      used in agriculture. The Ca concentration (420 g kg(-1); d.w.) was about 262
      times higher than the typical value of 1.6 g kg(-1) (d.w.) in arable land in
      Central Finland. However, the concentration Mg (0.2 g kg(-1); d.w.) in lime waste
      was equal to the Mg concentration in arable land in the Central Finland. The lime
      waste has strongly alkaline pH ( approximately 12.8) and a neutralizing value
      (i.e. liming effect) of 47.9% expressed as Ca equivalents (d.w.). This indicates
      lime waste to be a potential soil conditioner and improvement as well as a pH
      buffer.

PMID- 16887168
TI  - Is acid rain impacting the Sudetic lakes?
AB  - The diatoms and Cladocera (Crustacea) remains from two lakes in the Sudets
      Mountains were analyzed to indicate an influence of acidification induced by
      anthropogenic factors during the last 150 years. The border area of the Czech
      Republic, Germany and Poland, the so-called "Black Triangle", has been strongly
      impacted by developed industry for several decades. The most visible effect of
      this process is the destruction of mountain forests in the region by acid rains.
      The diatom communities of Maly Staw and Wielki Staw show that acid rain has
      strongly affected water biota. Diatom-inferred pH reconstruction suggests major
      acidification during the last two decades. This process was controlled mainly by
      anthropogenic factors. Cladoceran records also presented changes of dominant taxa
      in this period and point to significant changes in living conditions. The
      discovery of a pH decrease during the last decade is contradictory to emissions
      data that suggest decrease in industrial pollution.

PMID- 16887169
TI  - Mercury emissions to the atmosphere from anthropogenic sources in Europe in 2000
      and their scenarios until 2020.
AB  - The paper reviews the current state of knowledge regarding European emissions of
      mercury and presents estimates of European emissions of mercury to the atmosphere
      from anthropogenic sources for the year 2000. This information was then used as a
      basis for Hg emission scenario development until the year 2020. Combustion of
      coal in power plants and residential heat furnaces generates about half of the
      European emissions being 239 tonnes. The coal combustion is followed by the
      production of caustic soda with the use of the Hg cell process (17%). Major
      points of mercury emission generation in the mercury cell process include: by
      product hydrogen stream, end box ventilation air, and cell room ventilation air.
      This technology is now being changed to other caustic soda production
      technologies and further reduction of Hg emissions is expected in this
      connection. The third category on the list of the largest Hg emitters in Europe
      is cement production (about 13%). The largest emissions were estimated for Russia
      (the European part of the country), contributing with about 27% to the European
      emissions, followed by Poland, Germany, Spain, Ukraine, France, Italy and the
      United Kingdom. Most of these countries use coal as a major source of energy in
      order to meet the electricity and heat demands. In general, countries in the
      Central and Eastern Europe generated the main part of the European emissions in
      2000. Emission reductions between 20% and 80% of the 2000 emission amounts can be
      obtained by the year 2020, as estimated by various scenarios.

PMID- 16887170
TI  - Soil migration, plant uptake and volatilisation of radio-selenium from a
      contaminated water table.
AB  - The properties of (79)Se make it of likely potential importance in safety studies
      for geological disposal of radioactive wastes. Despite a substantial literature
      on toxic and nutritional aspects of selenium in the environment little
      consideration has been given to the behaviour of radioactive selenium and its
      potential transfer from a radioactive waste repository to the biosphere. Column
      experiments (15 x 50 cm), using a sandy loam soil, indicated that the upwards
      migration of (75)Se (as a surrogate for (79)Se) from a contaminated water table
      was dependent upon the redox status of the soil. Low redox conditions within the
      water table strongly limited upwards (75)Se soil migration, presumably due to the
      immobilisation of reduced Se species. Under natural conditions, (79)Se from a
      radioactive waste repository is therefore likely to accumulate at considerable
      depth. As a consequence, its absence from the rooting zone is likely to limit its
      transfer into plants. Nevertheless, the column experiments indicated that when an
      overlap between roots and soil contamination occurs, uptake into the plant is
      observed. Quantification of (75)Se volatilisation from the column surfaces
      suggested that this is a significant pathway by which (79)Se may move either
      directly from soil to the atmosphere, or from soil to plants and then to the
      atmosphere.

PMID- 16887171
TI  - Comparing the prothrombin time INR versus the APTT to evaluate the coagulopathy
      of acute trauma.
AB  - INTRODUCTION: In trauma patients, PT/INR or aPTT cutoffs of > or =1.5x normal are
      often used as triggers for the transfusion of plasma. MATERIAL AND METHODS: To
      evaluate the ability of the PT/INR or aPTT to predict low coagulation factor
      levels, these tests were compared to coagulation factor levels in samples with
      artificially prepared single and multiple factor deficiencies, 9 heparin
      contaminated samples, 10 lupus inhibitor-containing samples, 21 samples with
      elevated factor VIII levels, and 35 samples from acute trauma patients. RESULTS
      AND CONCLUSIONS: The PT/INR and aPTT showed comparable sensitivity for single or
      multiple factor deficiencies in artificially deficient plasmas, but the PT/INR
      was more sensitive than the aPTT to low coagulation factor levels in actual
      trauma patients (sensitivity 84% versus 50%). The aPTT can show false positives
      with lupus anticoagulants and heparin contamination and false negatives in
      samples with elevated factor VIII. Thus, in the acute trauma setting, the PT/INR
      cutoff is a more reliable indicator of reduced coagulation factor levels.

PMID- 16887173
TI  - Nrf2-Keap1 regulation of cellular defense mechanisms against electrophiles and
      reactive oxygen species.

PMID- 16887172
TI  - Ultrasound-facilitated thrombolysis using tissue-plasminogen activator-loaded
      echogenic liposomes.
AB  - INTRODUCTION: Targeted delivery of thrombolytics to the site of occlusion is an
      attractive concept, with implications for the treatment of many thrombo-occlusive
      diseases. Ultrasound enhances thrombolysis, which can be augmented by the
      addition of a contrast agent. We have previously reported development of
      echogenic liposomes (ELIP) for targeted highlighting of structures with potential
      for drug and gene delivery. This study evaluated the potential of ELIP for
      thrombolytic loading, and the effect of ultrasound exposure of thrombolytic
      loaded ELIP on thrombolytic efficacy. MATERIALS AND METHODS: Tissue-plasminogen
      activator (tPA) was loaded into ELIP. Echogenicity was assessed and reported as
      mean grayscale values. Whole porcine clots were treated with plasma, free tPA,
      tPA+Optison (echocontrast agent), or tPA-loaded ELIP, with and without ultrasound
      (1 MHz, continuous wave, 2 W/cm(2), for 2 min). Clots were weighed before and
      after a 30-min treatment period, and results reported as percent clot mass loss.
      RESULTS: tPA entrapment into ELIP was feasible with 50% entrapment, and retention
      of echogenicity. Treatment with tPA-loaded ELIP resulted in effective clot lysis
      with an effect similar to treatment with free tPA. Ultrasound exposure of tPA
      loaded ELIP resulted in enhanced thrombolysis (49.5% relative improvement vs. no
      ultrasound). Much of the ultrasound effect appeared to be related to drug release
      from the tPA-ELIP complex. CONCLUSIONS: We have demonstrated entrapment of tPA
      into ELIP with effective clot lysis and drug release using ultrasound. Our tPA
      loaded ELIP has potential for specific highlighting of clots to confirm agent
      delivery and help focus ultrasound therapy for targeted ultrasound-facilitated
      thrombolysis.

PMID- 16887174
TI  - Critical review of the methods used to measure the apparent dissociation constant
      and ligand purity in Ca2+ and Mg2+ buffer solutions.
AB  - Using simulated Ca2+ and Mg2+ buffers, methods proposed to measure both ligand
      purity and the apparent dissociation constant (Kapp) were investigated regarding
      (1) predicted accuracy of both parameters and (2) generality of the solution. The
      Bers' Ca2+ macroelectrode method [Bers, D. M., 1982 A simple method for the
      determination of free [Ca] in Ca-EGTA solutions Am. J. Physiol. 242, C404-C408]
      cannot be used with Mg2+ -macroelectrodes and is partly arbitrary since the
      linear part of the Scatchard plot is judged subjectively. Iterative methods have
      therefore been introduced. Iteration based on Bers' method or the lumped
      interference in the Nicolsky-Eisenman equation also failed with Mg2+
      macroelectrodes. The Oiki et al., method [Oiki, S., Yomamoto, T., Okada, Y.,
      1994. Apparent stability constants and purity of Ca-chelating agents evaluated
      using Ca-sensitive electrodes by the double-log optimization method Cell Calcium
      15, 209-46.] cannot be applied to Mg2+ macroelectrodes. The pH titration method
      of Moisescu and Pusch (Pflugers, Arch., 355, R122, 1975) predicted EGTA purity
      and Ca2+ contamination, but Kapp values for EGTA were approximate. It cannot be
      applied to Mg2+ binding. The partition method [Godt, R.E., 1974. Calcium
      activated tension of skinned muscle fibres of the frog. Dependence on magnesium
      adenosine triphosphate concentration J. Gen. Physiol. 63, 722-739.] only
      approximately estimated the K(app). Calibration, maintaining contaminating
      [Ca2+]/[Mg2+] at < 1micromol l(-1), and setting standards by dilution, is the
      ultimate check of calculated ionised concentrations, although technically
      difficult. The macroelectrode method of Luthi et al. [1997. Calibration of Mg2+ 
      selective macromolecules down to 1 micromol l(-1) in intracellular and Ca+ -
      containing extracellular solutions. Exp. Physiol. 82, 453-467] accurately
      predicted purity and Kapp at pKapp values > 4 and was independent of electrode
      characteristics. It is considered the method of choice. Macroelectrode primary
      calibration should be carried out in solutions varying from 0.5 to 10 mmol l(-1)
      combined with either Ca-EGTA or Mg-EDTA buffers; the [Ca2+] and [Mg2+] in other
      buffer ligands can be measured in a secondary calibration.

PMID- 16887176
TI  - Differently lasting effects of prenatal and postnatal chronic
      clozapine/haloperidol on activity and memory in mouse offspring.
AB  - We evaluated the behavioral effects of chronic haloperidol (HAL) and clozapine
      (CLO) during gestation and CNS development, compared with transient treatments
      that stopped 1-3 weeks before the test. RESULTS: 1) Chronic HAL (6 mg/l in
      drinking water) but not HAL-withdrawal caused hypo-activity in open-field test on
      postnatal days (PNDs) 35, 42 and 56. However, hyper-activity was found in both
      CLO (90 mg/l) and CLO-withdrawal pups. 2) In the step-through test, retention
      performance was significantly higher in HAL-treated mice than in the controls on
      PND 42, as well as in withdrawal mice on PNDs 35 and 42. However, both chronic
      CLO (90 mg/l) exposure and CLO-withdrawal tended to improve the acquisition of
      memory. Furthermore, chronic CLO (180 mg/l) ameliorated scopolamine (3 mg/kg)
      induced impairment of memory on PND 56. 3) In the water-maze test, both chronic
      HAL and HAL-withdrawal treatments significantly impaired performance on the 4th
      training day at PND 35, but not PNDs 42 and 56. Neither chronic CLO exposure nor
      CLO-withdrawal affected spatial memory. 4) Body weight following HAL/CLO
      administration decreased when compared with the controls during PND 21-35, but
      approached control levels at PND 40. CONCLUSION: HAL doesn't elicit permanent
      behavioral changes in offspring. By contrast, CLO had longer-lasting effects than
      HAL. The pups at age before PND 35 seem more sensitive to HAL/CLO than elder
      pups.

PMID- 16887175
TI  - Feasibility of ovarian preservation in patients with early stage endometrial
      carcinoma.
AB  - OBJECTIVES: Our objective was to determine the frequency of a coexisting ovarian
      malignancy and to evaluate the feasibility of ovarian preservation in patients
      with early stage endometrial carcinoma. METHODS: Endometrial cancer patients who
      received primary surgical treatment between 1992 and 2004 were identified using
      the institution's tumor registry. Information regarding patient age, preoperative
      and intraoperative evaluations, pathologic reports, and follow-up results was
      abstracted from medical records. RESULTS: Coexisting ovarian malignancy was
      detected in 19 (7.31%) of 260 patients who underwent surgical treatment (12
      metastatic and 7 synchronous primaries). The independent risk factors of a
      coexisting ovarian malignancy, as determined using a logistic regression model,
      were intraoperative extrauterine disease, non-endometrioid histology, lymph node
      metastasis, and patient age, and the presence of intraoperative extrauterine
      disease was found to most significantly predict ovarian involvement (OR=542.1;
      95% CI, 57.18 to 5139.23). Seventeen of the 19 cases showed abnormal
      intraoperative gross findings around adnexa or other sites. Among the 206
      patients without any evidence of intraoperative extrauterine disease, the
      coexisting ovarian malignancy rate was 0.97% (2/206), and zero for those under
      age of 45. In 35 patients, grossly normal ovaries were selectively saved, and no
      recurrence or cancer-related death occurred (median duration of follow-up: 76
      months, range 3-121). CONCLUSIONS: The risk of coexisting malignancy in patients
      without predictable risk factors is minimal. Therefore, it is possible to
      preserve ovaries in young women with early stage endometrial carcinoma with a
      thorough preoperative evaluation and extensive intraoperative exploration.

PMID- 16887177
TI  - Impaired drinking response in histamine H3 receptor knockout mice following
      dehydration or angiotensin-II challenge.
AB  - Histamine H3 receptors (H3Rs) are presynaptic receptors that negatively regulate
      the release of histamine. The present study examined the physiological role of
      H3Rs in drinking behavior. In water-replete rats, intracerebroventricular
      (i.c.v.) administration of R-alpha-methylhistamine (RalphaMeHA), an H3R agonist,
      elicited drinking behavior. In contrast, i.c.v. administration of thioperamide,
      an H3R inverse agonist, significantly attenuated the drinking behavior elicited
      by either overnight dehydration or i.c.v. administration of angiotensin-II (AT
      II). Inhibition of histamine release with alpha-fluoromethylhistidine, an
      inhibitor of histidine decarboxylase, did not elicit drinking behavior. Moreover,
      the inhibitory effects of thioperamide on drinking behavior in water-depleted
      rats were not mimicked by i.c.v. administration of histamine. These results
      suggest that the predominant effects of H3Rs on drinking behavior are not
      mediated by the modulation of histamine release. In H3R-deficient (H3RKO) mice,
      drinking behavior induced by overnight dehydration or i.c.v. administration of AT
      II was significantly impaired compared to wild type mice. Collectively, these
      observations suggest that brain H3Rs play a pivotal role in drinking behavior in
      response to dehydration and AT-II, and these effects may be largely independent
      of the modulation of histaminergic tone.

PMID- 16887178
TI  - Drosophila IKK-related kinase regulates nonapoptotic function of caspases via
      degradation of IAPs.
AB  - Caspase activation has been extensively studied in the context of apoptosis.
      However, caspases also control other cellular functions, although the mechanisms
      regulating caspases in nonapoptotic contexts remain obscure. Drosophila IAP1
      (DIAP1) is an endogenous caspase inhibitor that is crucial for regulating cell
      death during development. Here we describe Drosophila IKK-related kinase
      (DmIKKvarepsilon) as a regulator of caspase activation in a nonapoptotic context.
      We show that DmIKKvarepsilon promotes degradation of DIAP1 through direct
      phosphorylation. Knockdown of DmIKKvarepsilon in the proneural clusters of the
      wing imaginal disc, in which nonapoptotic caspase activity is required for proper
      sensory organ precursor (SOP) development, stabilizes endogenous DIAP1 and
      affects Drosophila SOP development. Our results demonstrate that DmIKKvarepsilon
      is a determinant of DIAP1 protein levels and that it establishes the threshold of
      activity required for the execution of nonapoptotic caspase functions.

PMID- 16887179
TI  - Speech perception in preschoolers at family risk for dyslexia: relations with low
      level auditory processing and phonological ability.
AB  - We tested categorical perception and speech-in-noise perception in a group of
      five-year-old preschool children genetically at risk for dyslexia, compared to a
      group of well-matched control children and a group of adults. Both groups of
      children differed significantly from the adults on all speech measures. Comparing
      both child groups, the risk group presented a slight but significant deficit in
      speech-in-noise perception, particularly in the most difficult listening
      condition. For categorical perception a marginally significant deficit was
      observed on the discrimination task but not on the identification task. Speech
      parameters were significantly related to phonological awareness and low-level
      auditory measures. Results are discussed within the framework of a causal model
      where low-level auditory problems are hypothesized to result in subtle speech
      perception problems that might interfere with the development of phonology and
      reading and spelling ability.

PMID- 16887181
TI  - Brief report: Binge drinking among high-risk male and female adolescents in
      Israel.
AB  - A major factor attributed to the problem and consequences of underage alcohol use
      is binge drinking. The objective of this study was to examine binge drinking and
      other alcohol-related problem behaviour among high-risk male and female
      adolescents who were from alternative schools and programs because of learning
      and/or behaviour problems. Self-report data were collected from a purposive
      sample of 917 adolescents in Israel who ranged from 12 to 18 years. Binge
      drinking during the last 30 days prior to the survey was reported by 33% of males
      and 23% of females (p<.001). Results of other alcohol-related behaviour showed
      gender status not related to being in a car when the driver had been drinking
      (12%) or having driven a car or motorcycle after drinking (5%). Multiple
      regression analysis showed binge drinking related to what a youth does with time;
      a decline in relations with family members; selling drugs; and, having been in a
      serious fight during the last 12 months. Country of origin, i.e. born in Israel
      or the Former Soviet Union, was not found linked to binge drinking. Further
      research of binge drinking and alcohol-related problem behaviour among high-risk
      youth is important so that it can be applied to immediate and longstanding
      prevention efforts.

PMID- 16887180
TI  - Delayed detection of tonal targets in background noise in dyslexia.
AB  - Individuals with developmental dyslexia are often impaired in their ability to
      process certain linguistic and even basic non-linguistic auditory signals. Recent
      investigations report conflicting findings regarding impaired low-level binaural
      detection mechanisms associated with dyslexia. Binaural impairment has been
      hypothesized to stem from a general low-level processing disorder for temporally
      fine sensory stimuli. Here we use a new behavioral paradigm to address this
      issue. We compared the response times of dyslexic listeners and their matched
      controls in a tone-in-noise detection task. The tonal signals were either Huggins
      Pitch (HP), a stimulus requiring binaural processing to elicit a pitch percept,
      or a pure tone-perceptually similar but physically very different signals. The
      results showed no difference between the two groups specific to the processing of
      HP and thus no evidence for a binaural impairment in dyslexia. However, dyslexic
      subjects exhibited a general difficulty in extracting tonal objects from
      background noise, manifested by a globally delayed detection speed.

PMID- 16887182
TI  - The effect of alpha-tocopherol on the oxidation and free radical decay in
      irradiated UHMWPE.
AB  - We developed a radiation cross-linked ultra-high molecular weight polyethylene
      (UHMWPE) stabilized with alpha-tocopherol (Vitamin E) as a bearing material in
      total joint replacements. The stabilizing effect of alpha-tocopherol on free
      radical reactions in UHMWPE is not well understood. We investigated the effect of
      alpha-tocopherol on the oxidation and transformation of residual free radicals
      during real-time aging of alpha-tocopherol-doped, irradiated UHMWPE (alphaTPE)
      and irradiated UHMWPE (control). Samples were aged at 22 degrees C (room
      temperature) in air, at 40 degrees C in air and at 40 degrees C in water for 7
      months. During the first month, alphaTPE showed some oxidation at the surface,
      which stayed constant thereafter. Control exhibited substantial oxidation in the
      subsurface region, which increased with time. The alkyl/allyl free radicals
      transformed to oxygen centered ones in both materials; this transformation
      occurred faster in alpha-TPE. In summary, the real-time oxidation behavior of
      alpha-TPE was consistent with that observed using accelerated aging methods. This
      new UHMWPE is oxidation resistant and is expected to maintain its properties in
      the long term.

PMID- 16887184
TI  - t(8;14)(q24;q32) in two patients with CD10-negative primary thyroid diffuse large
      B-cell lymphoma.
AB  - Diffuse large B-cell lymphoma (DLBCL) with the 8q24 translocation is occasionally
      seen in the gastrointestinal tract, but has rarely been reported in the thyroid
      gland. We experienced two cases of primary thyroid DLBCL having t(8;14)(q24;q32).
      The immunophenotype and karyotype of Case 1 (66-year-old female) and Case 2 (70
      year-old female) were: CD10-, CD20+, BCL-2+/add(13)(q34), t(8;14)(q24;q32) and
      CD10-, CD20-, CD79a+, BCL-2-/t(8;14)(q24;q32), respectively. Although long-term
      complete remission could be achieved in both of our patients by conventional
      chemotherapy with/without radiation therapy, accumulation of further such cases
      is necessary to develop a standard treatment protocol and also to elucidate the
      pathogenesis of t(8;14)(q24;q32)-positive primary thyroid DLBCL.

PMID- 16887183
TI  - Chemical and biological properties of supramolecular polymer systems based on
      oligocaprolactones.
AB  - We show that materials with a diverse range of mechanical and biological
      properties can be obtained using a modular approach by simply mixing different
      ratios of oligocaprolactones that are either end-functionalized or chain-extended
      with quadruple hydrogen bonding ureido-pyrimidinone (UPy) moieties. The use of
      two UPy-synthons allows for easy synthesis of UPy-modified polymers resulting in
      high yields. Comparison of end-functionalized UPy-polymers with chain-extended
      UPy-polymers shows that these polymers behave distinctively different regarding
      their material and biological properties. The end-modified UPy-polymer is rather
      stiff and brittle due to its high crystallinity. Disks made of this material
      fractures after subcutaneous implantation. The material shows a low inflammatory
      response which is accompanied by the formation of a fibrous capsule, reflecting
      the inertness of the material. The chain-extended UPy-material on the contrary is
      practically free of crystalline domains and shows clear flexible properties. This
      material deforms after in-vivo implantation, accompanied with cellular
      infiltration. By mixing both polymers, materials with intermediate properties
      concerning their mechanical and biological behaviour can be obtained.
      Surprisingly, a 20:80 mixture of both polymers with the chain-extended UPy
      polymer in excess shows flexible properties without visible deformation upon
      implantation for 42 days. This mixture, a blend formed by intimate mixing through
      UPy-UPy interaction, also shows a mild tissue response accompanied with the
      formation of a thin capsule. The material does not become more crystalline upon
      implantation. Hence, this mixture might be an ideal scaffold material for soft
      tissue engineering due to its flexibility and diminished fibrous tissue
      formation, and illustrates the strength of the modular approach.

PMID- 16887185
TI  - The innate immune response to grass carp hemorrhagic virus (GCHV) in cultured
      Carassius auratus blastulae (CAB) cells.
AB  - Virus infection of mammalian cells activates an innate antiviral immune response
      characterized by production of interferon (IFN) and the subsequent
      transcriptional upregulation of IFN-stimulated genes (ISGs) by the JAK-STAT
      signaling pathway. Here, we report that a fish cell line, crucian carp (Carassius
      auratus L.) blastulae embryonic (CAB) cells, can produce IFN activity and then
      form an antiviral state after infection with UV-inactivated grass carp
      hemorrhagic virus (GCHV), a double-stranded (ds) RNA virus. From UV-inactivated
      GCHV-infected CAB cells, 15 pivotal genes were cloned and sequenced, and all of
      them were shown to be involved in IFN antiviral innate immune response. These IFN
      system genes include the dsRNA signal sensing factor TLR3, IFN, IFN signal
      transduction factor STAT1, IFN regulatory factor IRF7, putative IFN antiviral
      effectors Mx1, Mx2, PKR-like, Viperin, IFI56, and other IFN stimulated genes
      (ISGs) IFI58, ISG15-1, ISG15-2, USP18, Gig1 and Gig2. The identified fish IFN
      system genes were highly induced by active GCHV, UV-inactivated GCHV, CAB IFN or
      poly(I).poly(C), and showed similar expression patterns to mammals. The data
      indicate that an IFN antiviral innate immune response similar to that in mammals
      exists in the UV-inactivated GCHV-infected CAB cells, and the IFN response
      contributes to the formation of an antiviral state probably through JAK-STAT
      signaling pathway. This study provides strong evidence for existence of IFN
      antiviral innate immune response in fish, and will assist in elucidating the
      origin and evolution of vertebrate IFN system.

PMID- 16887186
TI  - Evaluation of different phosphate amendments on availability of metals in
      contaminated soil.
AB  - A pot trial was conducted to assess the efficiency of P-induced metal
      immobilization in soils. Natural hydroxyapatite (HA), phosphate rock (PR), triple
      superphosphate (TSP), and diammonium phosphate (DAP) were evaluated for their
      ability to reduce cadmium (Cd), lead (Pb), and zinc (Zn) bioavailability in an
      artificially metal-contaminated soil with three addition levels: T0 (without
      metals added), T1 (Cd/Pb/Zn:0.6/100/66 mgkg(-1)), and T2 (Cd/Pb/Zn: 1.5/300/200
      mgkg(-1)). Phosphate compounds were applied at 2500 mg P(2)O(5) kg(-1) soil for
      each metal level with five treatments: CK (control), TSP, DAP, PR, and HA,
      respectively. The immobilization and bioavailability of Cd, Pb, and Zn were
      determined by plant (Brassica campestris L.) uptake, scanning electron microscope
      (SEM), and sequential extraction. The results showed that HA was superior to all
      other materials for reducing Pb, Zn, and Cd uptake in shoot with reductions of
      34.6-53.3% for Pb, 31.2-47.3% for Zn, and 39.1-42.4% for Cd, respectively, as
      compared with the control treatment. The mechanisms of Pb immobilization in the
      soil and the decreased Pb translocation from the plant root to shoot induced by
      added phosphate were identified with scanning electron microscope (SEM) equipped
      with energy dispersive X-ray elemental spectrometry (EDS). Sequential extraction
      results indicated that the phosphate amendments converted significant amounts of
      the soil Pb, Zn, and Cd from exchangeable (EX), organic bound (OC), carbonate
      bound (CB), amorphous Fe and Al oxides-bound (OX) (non-residual (RES) fractions)
      to RES fraction. In general, the effect of different phosphates on plant uptake
      of Pb, Zn, and Cd followed the order: HA>PR>DAP>TSP. The results suggested that
      HA and PR amendments could significantly reduce the bioavailability and increase
      the geochemical stability of soil Pb, Zn, and Cd in contaminated soils.

PMID- 16887187
TI  - Diffusion tensor imaging and aging.
AB  - Magnetic resonance diffusion tensor imaging (DTI) is a non-invasive in vivo
      method for characterizing the integrity of anatomical connections and white
      matter circuitry and provides a quantitative assessment of the brain's white
      matter microstructure. DTI studies reveal age-related declines in white matter
      fractional ansiotropy (FA) in normal healthy adults in whom volume declines are
      not necessarily detectable. The decline is equivalent in men and women, is linear
      from about age 20 years onwards, and has a frontal distribution. Studies
      combining regional DTI metrics and tests of specific cognitive and motor
      functions have shown that age-related declines in white matter integrity are
      associated with similar declines in interhemispheric transfer, especially
      dependent on frontal systems. Emerging from recent DTI findings and
      conceptualizations of neural causes of cognitive decline in aging, we propose
      three white matter-mediated neural system hypotheses of aging brain structure and
      function: (1) the anteroposterior gradient, (2) bilateral recruitment of brain
      systems via the corpus callosum for frontally based task execution, and (3)
      frontocerebellar synergism. These hypotheses are not mutually exclusive but
      establish a basis for posing testable questions about brain systems recruited
      when those used in youth are altered by aging.

PMID- 16887188
TI  - Brain development in children and adolescents: insights from anatomical magnetic
      resonance imaging.
AB  - Advances in neuroimaging have ushered in a new era of developmental neuroscience.
      Magnetic resonance imaging (MRI) is particularly well suited for pediatric
      studies because it does not use ionizing radiation which enables safe
      longitudinal scans of healthy children. Key findings related to brain anatomical
      changes during childhood and adolescent are increases in white matter volumes
      throughout the brain and regionally specific inverted U-shaped trajectories of
      gray matter volumes. Brain morphometric measures are highly variable across
      individuals and there is considerable overlap amongst groups of boys versus
      girls, typically developing versus neuropsychiatric populations, and young versus
      old. Studies are ongoing to explore the influences of genetic and environmental
      factors on developmental trajectories.

PMID- 16887189
TI  - DAF/Crry double deficiency in mice exacerbates nephrotoxic serum-induced
      proteinuria despite markedly reduced systemic complement activity.
AB  - Decay-accelerating factor (DAF) and complement receptor 1-related gene/protein y
      (Crry) are two membrane-anchored complement regulatory proteins in rodent.
      Although both proteins are broadly distributed and exert complement regulation at
      the same steps of the complement cascade, DAF knockout mice are viable whereas
      Crry knockout mice die in utero as a result of maternal complement attack. The
      latter outcome has prevented the dissection of overlapping functions of DAF and
      Crry in adult mouse tissues in vivo. By crossing female DAF(-/-)/Crry(-/-)/C3(-/
      ) mice with male DAF(-/-)/Crry(+/-)/C3(+/-) mice, we circumvented maternal
      complement attack during fetal development and generated viable DAF(-/-)/Crry(-/
      )/C3(+/-) mice to address the consequence of DAF/Crry double deficiency. DAF(-/
      )/Crry(-/-)/C3(+/-) mice were born at the expected frequency and survived to
      adulthood. However, they were found to have greatly reduced systemic complement
      activity due, at least in part, to spontaneous C3 activation and consumption.
      Plasma C3 proteins in DAF(-/-)/Crry(-/-)/C3(+/-) mice were 30% of that of wild
      type mice, and serum complement activity, as assessed by zymosan and immune
      complex C3 opsonization assays, was 90% reduced in DAF(-/-)/Crry(-/-)/C3(+/-)
      mice. Remarkably, despite greatly reduced systemic complement activity, DAF(-/
      )/Crry(-/-)/C3(+/-) mice developed more severe proteinuria after induction of
      nephrotoxic serum nephritis as compared with DAF(-/-)/Crry(+/-)/C3(+/-) and DAF(
      /-)/Crry(-/-)/C3(-/-) littermate controls. The results highlight the critical and
      overlapping role of Crry and DAF in vivo in preventing complement activation and
      tissue injury.

PMID- 16887190
TI  - Comment on "Thwaites et al., 2005, The influence of HIV infection on clinical
      presentation, response to treatment, and outcome in adults with Tuberculous
      meningitis" J Infect Dis. 2005 Dec 15;192(12):2134-41.

PMID- 16887191
TI  - Performance of a predictive rule to distinguish bacterial and viral meningitis.
AB  - OBJECTIVE: Although diagnostic performance has recently improved by using new
      diagnostic methodologies, acute patient management is usually initiated after
      considering only fairly elementary findings of CSF examination. Using these early
      findings it is often difficult to distinguish between bacterial and aseptic
      (viral) meningitis. In order to help distinguish these two categories, scoring
      tools have been proposed that are more or less complex and validated. METHODS:
      The aim of this study was to establish a simple scoring tool and compare it to
      other available decision making systems. We retrospectively analysed all the
      meningitis cases from our patients at our institution and established a scoring
      tool for pediatric meningitis and for meningitis in adults by using categorized
      analysis tree methodology. RESULTS: Main categories for bacterial etiology were,
      leucocytosis >15 giga, CSF leucocytes count >1700 per ml, CSF neutrophil
      percentage >80, CSF protein >2.3g/l and glucose CSF/blood ratio <0.33 for adults
      and CSF leucocytes count >1800, CSF neutrophil percentage >80, CSF protein
      >1.2g/l and glucose CSF/blood ratio <0.3 for children. Additionally, our new
      scoring tool and five published ones were compared using our data and two
      external data sets; from these scores, three, including ours, exhibited good
      sensitivity and specificity. We then performed several thousand Monte Carlo
      simulations of both bacterial and viral meningitis for children and adults. We
      found that our scoring tool (Meningitest) had very high performances with
      positive and negative predictive values of 97% and 94%, respectively. CONCLUSION:
      Thus, from this analysis of five meningitis scoring systems, we believe that our
      new tool is simple, does not need any complex calculation and is effective in
      identifying bacterial vs viral meningitis in fully immunocompetent children and
      adults.

PMID- 16887192
TI  - EEG alpha oscillations: the inhibition-timing hypothesis.
AB  - The traditional belief is that the event-related alpha response can solely be
      described in terms of suppression or event-related desynchronization (ERD).
      Recent research, however, has shown that under certain conditions alpha responds
      reliably with an increase in amplitudes (event-related synchronization or ERS).
      ERS is elicited in situations, where subjects withhold or control the execution
      of a response and is obtained over sites that probably are under, or exert top
      down control. Thus, we assume that alpha ERS reflects top-down, inhibitory
      control processes. This assumption leads over to the timing aspect of our
      hypothesis. By the very nature of an oscillation, rhythmic amplitude changes
      reflect rhythmic changes in excitation of a population of neurons. Thus, the time
      and direction of a change - described by phase - is functionally related to the
      timing of neuronal activation processes. A variety of findings supports this view
      and shows, e.g., that alpha phase coherence increases between task-relevant sites
      and that phase lag lies within a time range that is consistent with neuronal
      transmission speed. Another implication is that phase reset will be a powerful
      mechanism for the event-related timing of cortical processes. Empirical evidence
      suggests that the extent of phase locking is a functionally sensitive measure
      that is related to cognitive performance. Our general conclusion is that alpha
      ERS plays an active role for the inhibitory control and timing of cortical
      processing whereas ERD reflects the gradual release of inhibition associated with
      the emergence of complex spreading activation processes.

PMID- 16887193
TI  - An ex vivo preparation of mature mice spinal cord to study synaptic transmission
      on motoneurons.
AB  - Mammalian spinal cord motoneurons are highly susceptible to chemical and
      mechanical disturbances, which imposes substantial difficulties for
      electrophysiological investigation in acute in vitro preparations. The aim of the
      present study was to establish an isolated spinal cord preparation from adult
      mice and to examine the synaptic activities of motoneurons in vitro. We removed
      the lumbo-sacral cord from the vertebral canal by hydraulic extrusion and
      maintained the isolated cord in vitro for extracellular recordings. Population
      spikes of motoneurons were evoked by electrical stimulation of dorsal roots
      (orthodromic) or ventral roots (antidromic) and these evoked responses could be
      continuously monitored for 5-6 h. The orthodromic population spikes were
      reversibly suppressed by the AMPA/kainate receptor antagonist 2,3-dihyro-6-nitro
      7-sulfamoylbenzo quinoxaline (NBQX, 10 microM) but they persisted in the presence
      of the NMDA receptor antagonist D(-)-2-amino-5-phosphonovaleric acid (AP5, 50
      microM). The antidromic population spikes exhibited evident paired pulse
      inhibition when evoked at inter-stimulus intervals of pound 6 ms. Histological
      examination revealed that basic morphological features of the lumbo-sacral
      motoneurons were preserved after 3-4 h of in vitro maintenance. This in vitro
      preparation is ideally suited for the electrophysiological study of synaptic
      transmission on adult mouse spinal motoneurons.

PMID- 16887194
TI  - A tool for synthesizing spike trains with realistic interference.
AB  - Spike detection and spike sorting techniques are often difficult to assess
      because of the lack of ground truth data (i.e., spike timings for each neuron).
      This is particularly important for in vitro recordings where the signal to noise
      ratio is poor (as is the case for multi-electrode arrays at the bottom of a cell
      culture dish). We present an analysis of the transmission of intracellular
      signals from neurons to an extracellular electrode, and a set of MATLAB functions
      based on this analysis. These produce realistic signals from neighboring neurons
      as well as interference from more distant neurons, and Gaussian noise. They thus
      generate realistic but controllable synthetic signals (for which the ground truth
      is known) for assessing spike detection and spike sorting techniques. They can
      also be used to generate realistic (non-Gaussian) background noise. We use
      signals generated in this way to compare two automated spike-sorting techniques.
      The software is available freely on the web.

PMID- 16887195
TI  - Localized and non-contact mechanical stimulation of dorsal root ganglion sensory
      neurons using scanning ion conductance microscopy.
AB  - Mechanosensitive ion channels convert external mechanical force into electrical
      and chemical signals in cells, but their physiological function in different
      tissues is not clearly understood. One reason for this is that there is as yet no
      satisfactory physiological method to stimulate these channels in living cells.
      Using the nanopipette-probe of the Scanning Ion Conductance Microscope (SICM), we
      have developed a new technique to apply local mechanical stimulus to living cells
      to an area of about 0.385 microm2, determined by the pipette diameter. Our method
      prevents any physical contact and damage to the cell membrane by use of a
      pressure jet applied via the nanopipette. The study used whole-cell patch-clamp
      recordings and measurements of intracellular Ca2+ concentration to validate the
      application of the mechanical stimulation protocols in human and rat dorsal root
      ganglia (DRG) sensory neurons. We were able, for the first time, to produce a non
      contact, controlled mechanical stimulation on living neurites of human DRG
      neurons. Our methods will enable the identification and characterisation of
      compounds being developed for the treatment of clinical mechanical
      hypersensitivity states.

PMID- 16887196
TI  - Peripheral nerve morphometry: Comparison between manual and semi-automated
      methods in the analysis of a small nerve.
AB  - Manual nerve morphometry has been usually described as tedious, time consuming,
      difficult to perform correctly and subject to many sources of errors. The above
      considerations might suggest that fully automated image analysis systems could be
      ideally programmed to analyze myelinated fibers. However, operator intervention
      is necessary to manually eliminate dark tissue elements such as pericytes and
      Schwann cell nuclei. The aims of the present study were to compare the manual and
      semi-automated techniques in the evaluation of a small nerve, comparing the most
      commonly used morphometric parameters for nerve descriptions. The aortic
      depressor nerves (ADN) of male Wistar rats (N = 12) were prepared with
      conventional techniques for epoxy resin embedding. Manual morphometry was
      performed on photomicrographs using a digitizing tablet. Semi-automated
      morphometry was performed with the aid of computer software, on the same negative
      images used on the photographic procedure, which were scanned and digitized to a
      microcomputer. Our results show no differences between data obtained with both
      methods, for any of the evaluated parameters (area, perimeter, diameters, myelin
      sheath thickness, g ratio, distribution histograms). In conclusion, manual
      morphometry reproduced data obtained with semi-automated technique in a small
      nerve, with the advantages of being less-expensive and an affordable method.

PMID- 16887197
TI  - Stimulus waveform influences the efficacy of repetitive transcranial magnetic
      stimulation.
AB  - BACKGROUND: Optimising stimulus parameters is important in maximising the
      efficacy of repetitive transcranial magnetic stimulation (rTMS) in treatment
      applications. RTMS over motor cortex has been reported as more effective in
      producing corticospinal inhibition when a monophasic rather than a biphasic
      stimulus waveform is used. However, non-optimal coil orientation and high
      intensities of monophasic rTMS may have influenced previous results. METHODS: In
      eight healthy subjects, we measured motor evoked potentials (MEPs) in a hand
      muscle after monophasic and biphasic rTMS (1 Hz for 15 min) over the motor cortex
      with the coil always in the optimal orientation. MEPs were evoked by both
      monophasic and biphasic stimuli. RESULTS: MEPs were initially significantly
      reduced after monophasic but not biphasic rTMS. However, a late reduction was
      seen after biphasic rTMS. LIMITATIONS: These motor cortical findings may not be
      directly applicable to prefrontal rTMS. CONCLUSIONS: This study confirms that low
      frequency rTMS with monophasic pulses produces more corticospinal inhibition than
      with biphasic pulses, even when the direction of current and intensity are as
      well-matched as possible.

PMID- 16887198
TI  - An exploration of the patient's experience of electro-convulsive therapy in mid
      twentieth century creative literature: a historical study with implications for
      practice today.
AB  - BACKGROUND: Understanding a patient's subjective experience of electro-convulsive
      therapy (ECT) is important. Creative literature may both express such experiences
      and influence how ECT is perceived since scenarios and characters in literature
      become incorporated into cultural stereotypes and mythologies. Clinical
      discussions with patients and their families suggest that One Flew over the
      Cuckoo's Nest still has an impact on their perceptions of ECT, and therefore
      still has clinical relevance today. This study aims to explore experiences of ECT
      through creative literature focussing on novels from the 1960s. METHOD: Study of
      three novels depicting ECT in their historical context. RESULTS: Various factors
      identified in the books studied may be associated with reluctance to accept ECT
      as a treatment, in particular images related to electricity. LIMITATIONS: Since
      this is a historical survey rather than a clinical research project, and is based
      on creative literature, it may not reflect 21st century reality. CONCLUSIONS:
      Fear of electricity and other factors in the practice of ECT in the past may
      still be important in the acceptance of ECT as a clinical treatment. This
      warrants further qualitative exploration.

PMID- 16887199
TI  - Non-suicidal self-injury among adolescents: diagnostic correlates and relation to
      suicide attempts.
AB  - Non-suicidal self-injury (NSSI) is a prevalent behavioral problem, yet many
      fundamental aspects of NSSI remain unknown. This case series study reports on the
      diagnostic correlates of adolescents with a recent history of NSSI and examines
      the relation between NSSI and suicide attempts. Data are from clinical interviews
      with 89 adolescents admitted to an adolescent psychiatric inpatient unit who
      engaged in NSSI in the previous 12 months. Results revealed that 87.6% of
      adolescents engaging in NSSI met criteria for a DSM-IV Axis I diagnosis (M=3.0,
      S.D.=2.2, range=0 to 8 diagnoses), including externalizing (62.9%), internalizing
      (51.7%), and substance use (59.6%) disorders. Most adolescents assessed also met
      criteria for an Axis II personality disorder (67.3%). Overall, 70% of adolescents
      engaging in NSSI reported a lifetime suicide attempt and 55% reported multiple
      attempts. Characteristics of NSSI associated with making suicide attempts
      included a longer history of NSSI, use of a greater number of methods, and
      absence of physical pain during NSSI. These findings demonstrate the diagnostic
      heterogeneity of adolescents engaging in NSSI, highlight the significant overlap
      between NSSI and suicide attempts, and provide a point of departure for future
      research aimed at elucidating the relations between non-suicidal and suicidal
      self-injury.

PMID- 16887200
TI  - Evaluation of methods used to concentrate and detect hepatitis A virus in water
      samples.
AB  - Two adsorption-elution concentration methods, both involving negatively charged
      membranes, were evaluated in order to monitor hepatitis A virus (HAV)
      contamination in tap, river, mineral and coastal water samples: elution with urea
      arginine phosphate buffer/reconcentration with magnesium chloride (method 1); and
      sodium hydroxide elution/reconcentration with a commercial concentrator (method
      2). Nested (qualitative) reverse transcriptase PCR (RT-PCR) and real-time
      (quantitative) RT-PCR were used to detect and quantify HAV RNA in concentrated
      water samples. For concentrating HAV, method 1 was found to be the most suitable
      for tap water and method 2 most suitable for mineral water. HAV inoculated
      experimentally was detected in river water samples by both methods and in coastal
      water samples by neither method. The detection limits were 6 x 10(9) g equiv./ml
      for qualitative PCR and 60 g equiv./ml for quantitative PCR. In a field
      application study, HAV was detected in 20% of river and tap water samples but not
      in coastal or mineral water samples. River water samples contained subgenotype
      IA, and tap water samples contained subgenotype IB. It is concluded that,
      although influencing qualitative PCR, the concentration method does not affect
      quantitative PCR, which could therefore be used for all types of water samples.
      Both techniques are recommended for detecting HAV in environmental water samples.

PMID- 16887201
TI  - Effects of sex on object recognition and spatial navigation in humans.
AB  - Human tests designed to mirror rodent tests of object recognition and spatial
      navigation were administered to adult cognitively healthy humans. Facial
      recognition was also assessed. There was no sex difference in facial recognition,
      consistent with earlier studies. In the object recognition test, the test-retest
      NINL total scores during the same visit were highly correlated, comparable to the
      test-retest correlations obtained in the established facial recognition test.
      There were no effects of sex on object recognition. However, in the spatial
      navigation test, there were effects of sex on spatial learning and memory during
      the session with the hidden, but not visible, target. These tests might be useful
      to compare assessments of object recognition and spatial learning and memory in
      humans and animal models.

PMID- 16887202
TI  - The role of the subiculum within the behavioural inhibition system.
AB  - This paper summarises the picture of the subiculum presented by Gray and
      McNaughton [Gray JA, McNaughton N. The neuropsychology of anxiety: an enquiry
      into the functions of the septo-hippocampal system. Oxford: Oxford University
      Press; 2000]. It is a key node in their "Behavioural Inhibition System" and, as
      such, is embedded within a hierarchy of structures controlling anxiety that is in
      parallel with a separate hierarchy controlling fear. It can nonetheless be viewed
      as operating in a fairly simple manner. It receives information about available
      goals from areas that plan motor action. This is filtered by earlier elements of
      the essentially unidirectional hippocampal circuit that essentially block
      familiar and unimportant information while passing to the subiculum important
      information. The function of the subiculum is to compare and integrate this goal
      information and produce output when conflict between incompatible goals is
      detected. This output prevents execution of the responses that would address the
      conflicting goals, increases the valence of affectively negative stimuli and
      associations and releases external exploration and internal rumination intended
      to resolve the conflict. These subicular outputs are held to be computationally
      simple but to have complex consequences both because of the complexity of the
      target areas and because, in many cases, processing is recursive. It can involve
      multiple passages of essentially the same information round loops such as the
      circuit of Papez--each pass refining the solution to the original problem of
      conflicting goals.

PMID- 16887203
TI  - Hippocampal partial kindling decreased hippocampal GABAB receptor efficacy and
      wet dog shakes in rats.
AB  - To test the hypothesis that GABA(B) receptor efficacy in the behaving rat
      decreases after partial hippocampal kindling, we measured GABA(B) receptor
      efficacy by the number of wet dog shakes (WDSs) induced by baclofen (5mM in
      0.2muL of saline) infusion into the dorsal hippocampus; these WDSs were blocked
      by prior infusion of GABA(B) receptor antagonist CGP55845A. Rats were given 15
      afterdischarges (ADs) evoked in CA1 over 3 days or control stimulations. The
      partially kindled rats (after 15 ADs) showed a significant decrease in baclofen
      induced WDSs as compared to control rats, on days 1, 4 and 21 after kindling. In
      contrast, kindled and control rats did not show a significant difference in WDSs
      induced by hippocampal infusion of GABA(A) receptor antagonist bicuculline. Also,
      the number of WDSs induced after subcutaneous injection of serotonin-2A/2C
      agonist+/-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane was not different between
      kindled and control rats on 4 and 21 days after kindling. We further tested the
      hypothesis that the decrease in hippocampal AD-induced WDSs during kindling is
      caused by a decrease in GABA(B) receptor efficacy. However, we found no
      convincing evidence to support the latter hypothesis since the AD-induced WDSs
      were not suppressed by hippocampal infusion of CGP55845A, with the exception that
      CGP55845A infusion into ventral hippocampus suppressed both hippocampal ADs and
      WDSs. Together with results derived from previous electrophysiological studies in
      vitro, it is suggested that a decrease of GABA(B) receptor, possibly GABA(B)
      autoreceptor, efficacy may explain the decrease of baclofen-induced WDSs after
      hippocampal kindling.

PMID- 16887204
TI  - Mouse lines selected for difference in sensitivity to beta-CCM also differ in
      memory processes.
AB  - Methyl-beta-carboline-3-carboxylate (or beta-CCM) is a benzodiazepine receptor
      ligand with inverse agonist properties. Two strains of mice were selected, one
      for sensitivity (BS) and one for resistance (BR) to a convulsive dose of beta
      CCM. These two strains were then shown to differ in several biochemical,
      pharmacological and behavioral characteristics; specifically BS mice were less
      anxious than BR mice. The present work provides evidence of differences in the
      learning abilities of the two strains. Three different learning tasks were used:
      spatial delayed discrimination on the 4-hole board, a learned choice between a
      lit and a dark compartment in a T-maze, and place-learning in an 8-arm radial
      maze. In all three tasks, BS mice had consistently better performance levels than
      BR mice.

PMID- 16887205
TI  - Evidence of genotoxicity related to high PAH content of sediments in the upper
      part of the Seine estuary (Normandy, France).
AB  - In order to characterize the genotoxicity in the Seine estuary and Seine bay,
      chemical and toxicological analyses were performed on 17 sediments collected in
      June 2001 and June 2003. Many potent mutagenic and/or carcinogenic compounds -
      including polycyclic aromatic hydrocarbons (PAH), polychlorinated biphenyls (PCB)
      and metals - were detected. Those compounds were found to be at relatively high
      concentrations in the upper part of the Seine estuary but were barely detectable
      at sites outside the plume from the Seine. The levels of pollution did not vary
      significantly between the two sampling periods, except that PAH concentrations in
      sediments collected at Oissel and Le Havre showed a marked increase in June 2003.
      The toxicity of organic extracts from sediments was evaluated by both
      embryotoxicity and in vitro genotoxicity (SOS Chromotest) assays. Organic
      extracts from sediments taken from the Seine estuary appeared significantly more
      embryotoxic than those from the Seine bay. In addition, the sediment extracts
      from the upper part of the Seine estuary exhibited higher genotoxicity than those
      from the lower part, and no genotoxicity was reported for sediments from the
      Seine bay. The genotoxic activity was detected only after adding an S9 microsomal
      fraction, suggesting the preponderant involvement of pro-genotoxic organic
      compounds. In addition, SOS Chromotest responses obtained with purified organic
      fractions revealed that PAH and, to a lesser extent, unknown polar organic
      compounds were probably responsible for this genotoxicity. Altogether, these
      results suggest that sediments from the upper Seine estuary are genotoxic and
      embryotoxic, and therefore, could be potentially hazardous for species living or
      feeding in the area.

PMID- 16887206
TI  - Temperature-dependent stress response in oysters, Crassostrea virginica:
      pollution reduces temperature tolerance in oysters.
AB  - Combined effects of temperature and a toxic metal, cadmium (Cd), on energy
      metabolism were studied in a model marine bivalve, the eastern oyster Crassostrea
      virginica, acclimated at 20, 24 and 28 degrees C and exposed to 50microgl(-1) of
      Cd. Both increasing temperature and Cd exposure led to a rise in standard
      metabolic rates, and combined stressors appeared to override the capability for
      aerobic energy production resulting in impaired stress tolerance. Oysters exposed
      to elevated temperature but not Cd showed no significant change in condition,
      survival rate and lipid peroxidation, whereas those exposed to both Cd and
      temperature stress suffered high mortality accompanied by low condition index and
      elevated lipid peroxidation. Furthermore, RNA/DNA ratios indicative of protein
      synthesis rate, and levels of glutathione, which is involved in metal
      detoxification, increased in Cd-exposed oysters at 20 degrees C but not at 28
      degrees C. Implications of the synergism between elevated temperatures and
      cadmium stress on energy metabolism of oysters are discussed in the light of the
      potential effects of climate change on oyster populations in polluted areas.

PMID- 16887207
TI  - Divalent metal requirements for catalysis and stability of the RNA triphosphatase
      from Trypanosoma cruzi.
AB  - RNA triphosphatases act in the first step of the mRNA capping process, removing
      the gamma-phosphoryl group from the 5' end of nascent RNA. A metal-dependent
      catalysis is found in the enzymes from trypanosomes and several other lower
      eukaryotes. This contrasts with the cysteine-dependent activity of the
      corresponding enzymes of mammals, a difference that points to these enzymes as
      potential targets for drug design. This work describes the identification,
      expression, purification, enzyme kinetics, and the role of divalent metal in the
      ATPase activity of the RNA triphosphatase from Trypanosoma cruzi, the agent of
      Chagas' disease, and compares it with the previously characterized enzyme from
      Trypanosoma brucei. Sequence similarity of the T. cruzi enzyme with the RNA
      triphosphatase of Saccharomyces cerevisiae indicates that a tunnel domain
      containing the divalent metal forms its active site. Based on enzyme kinetics,
      circular dichroism, and intrinsic fluorescence analysis, a kinetic mechanism for
      the ATPase activity of the T. cruzi tunnel triphosphatase is proposed. A single
      metal is sufficient to interact with the enzyme through the formation of a
      productive MnATP-enzyme complex, while free ATP inhibits activity. Manganese is
      also required for the tunnel stability of the T. cruzi enzyme, while the T.
      brucei homologue remains stable in the absence of metal, as shown for other
      triphosphatases. These findings may be useful to devise specific triphosphatase
      inhibitors to the T. cruzi enzyme.

PMID- 16887208
TI  - Cytoplasmic Ca2+ signals and cellular death by apoptosis in myocardiac H9c2
      cells.
AB  - The incubation of H9c2 cells with 10 microM thapsigargin (TG) was associated with
      the appearance of a two-component cytoplasmic Ca2+ peak. Experiments performed in
      a Ca2+-free medium indicated that both components came from intracellular
      sources. The first component of the signal corresponded to the discharge of the
      sarco-endoplasmic reticulum (SER) Ca2+ store. The appearance of the second
      component was prevented by cell preincubation with cyclosporin A (CsA) and gave
      rise to a clear and permanent depolarization of the mitochondrial inner membrane.
      These features were indication of a mitochondrial origin. The observed release of
      mitochondrial Ca2+ was related with opening of the permeability transition pore
      (PTP). The two-component cytoplasmic Ca2+ peak, i.e., treatment with 10 microM
      TG, as compared with the first component alone, i.e., treatment with 3 microM TG,
      was associated with a faster process of cellular death. In both cases, chromatin
      fragmentation and condensation at the nuclear periphery were observed. Other
      prominent apoptotic events such as loss of DNA content and cleavage of poly(ADP
      ribose) polymerase (PARP) were also dependent on TG concentration and occurred in
      different time windows. PTP opening induced by 10 microM TG was responsible for
      the faster apoptotic death.

PMID- 16887209
TI  - SAECG parameters and left ventricular chamber sizes: lesson from anemia
      conditions in thalassemia major patients.

PMID- 16887210
TI  - Results of the Women's Health Study of Accra: assessment of blood pressure in
      urban women.
AB  - BACKGROUND: The Women's Health Study of Accra was conducted to determine the
      burden of illness in a representative sampling of adult urban women. METHODS:
      This community-based survey selected study participants by a 2-stage cluster
      probability sample stratified by socioeconomic status based on the 2000 Ghanaian
      census data. It included a comprehensive household survey and medical and
      laboratory examination for 1328 women. Hypertension was defined as systolic blood
      pressure measurement > or = 140 mmHg or a diastolic of > or = 90 mmHg. RESULTS: A
      positive review of systems for hypertension was reported in 309 (23.7%) with only
      52.5% using anti-hypertensive medication and only 4.4% had a normal blood
      pressure. The blood pressure measurement was elevated in 712/1303 (54.6%).
      Significant risk factors for an elevated blood pressure included age > or = 50
      years (OR=14.24 [10.74,18.8], p<0.001); BMI > or = 30.00 (OR=2.89 [2.26,3.70],
      p<0.001); parity of three or more children (OR=5.16 [2.90,9.19], p<0.001);
      menopause before age 50 years (OR=5.88 [1.11,31.17], p=0.037); elevated fasting
      blood glucose (OR=3.98 [2.38,6.64], p<0.001); elevated fasting cholesterol
      (OR=1.69 [1.24, 2.30], p=0.001); no formal education (OR=2.75 [1.70,4.43],
      p<0.001) and first degree family history of hypertension (p<0.001). There was no
      association with income level, diet or activity. Significant protective factors
      include young age, nulliparity, normal BMI, and a lower than normal fasting LDL
      cholesterol. CONCLUSION: The prevalence of presumptive hypertension is greater
      than anticipated. Public health initiatives to increase awareness of hypertension
      and to initiate and maintain treatment regimens will serve to improve the health
      of the women and the urban community.

PMID- 16887211
TI  - Autoantibodies to cardiac troponin I in patients with idiopathic dilated and
      ischemic cardiomyopathy.
AB  - BACKGROUND: Progressive dilatation and functional compromise of heart function is
      attributed to a variety of pathogenic mechanisms. Experimental data suggests that
      autoantibodies could promote myocardial damage by inducing either inflammation or
      alternatively, augmentation of Ca2+ currents or activation of surface receptors
      on cardiomyocytes. Cardiac troponin I (cTpnI) is an essential protein component
      of the contractile heart. Herein, we studied the presence and functional
      properties of autoantibodies to cTpnI in patients with idiopathic dilated
      cardiomyopathy (DCM) and ischemic cardiomyopathy (ICM). METHODS AND RESULTS: Anti
      cTpnI antibody ELISA was established for assessment of sera obtained from 33
      patients with ICM, 32 with DCM and 42 healthy subjects. Binding specificity of
      purified cTpnI-reactive IgG fractions from patients with ICM and DCM was
      confirmed by competitive inhibition studies employing fluid-phase cTpnI. The
      effect of IgG preparations on intracellular Ca2+ ([Ca2+]i) transients was tested
      in cultured neonatal rat ventricular myocytes (NRVM). Six of the 33 ICM patients
      (18.2%) and 5 of the 32 DCM patients (15.6%) had positive anti-cTpnI antibody
      titer as compared to none in the healthy subjects. Purified IgG from positive
      patients appeared specific to cTpnI. IgG preparations reactive with cTpnI did not
      exhibit measurable effects on [Ca2+]i transients in cultured NRVM nor did they
      bind the respective cells by direct immunofluorescence. CONCLUSION: IgG
      antibodies to TpnI are increased in a significant number of patients with both
      ICM and idiopathic DCM, yet it appears that these autoantibodies cannot bind
      heart muscle cells or influence [Ca2+]i transients.

PMID- 16887212
TI  - CardioSignal: a database of transcriptional regulation in cardiac development and
      hypertrophy.
AB  - BACKGROUND: Although extensive research has characterized intricate genetic
      programs in heart system, the information generated is highly fragmented. Here we
      have developed a new database called CardioSignal, which was designed for
      integration of regulatory information on the transcriptional regulation involved
      in heart development and cardiac hypertrophy. METHODS: Data about sequences,
      positions and functional annotation of transcription binding sites, cis
      regulatory modules as well as promoters were collected from scientific
      literature. Genes involved in both processes were also manually gathered,
      particularly those preferentially expressed in the heart. Data was stored in
      MySQL database and Perl was used as the server-side programming language.
      RESULTS: Currently, CardioSignal contains 677 cardiac genes from twenty species.
      Among them are 128 cardiac transcription factors. Of the approximately 179
      individual promoters from six species, the database also documented 247
      experimentally verified binding sites and 64 cis-regulatory modules. CardioSignal
      may be searched for the promoter of a specific gene by specifying a gene name,
      Entrez geneID, swissProt accession number and so on. Downstream targets of
      transcriptional factors and cardiac regulatory modules can also be retrieved
      through a user-friendly web interface. Also available is experimental supporting
      evidence. Computational analysis tools were implemented for on-the-fly motif
      finding and comparative genomic analysis respectively. CONCLUSIONS: CardioSignal
      offers a unique resource as it contains simultaneously the promoter collected
      while correlating the information of transcription factor binding sites and cis
      regulatory modules from heart system. We are hopeful that its implementation will
      contribute toward the elucidation of the complex processes in cardiac development
      and hypertrophy.

PMID- 16887214
TI  - Elevated levels of platelet-monocyte aggregates and related circulating
      biomarkers in patients with acute coronary syndrome.
AB  - AIMS: To investigate whether patients with acute coronary syndrome (ACS)
      possessed high levels of platelet-monocyte aggregates (PMAs) and related
      circulating biomarkers. METHODS: 74 ACS patients, 58 stable angina pectoris (SAP)
      patients and 46 control patients without coronary artery disease were selected
      and their PMAs were measured by flow cytometry. Their plasma IL-6, IL-8, MCP-1,
      soluble CD40L and soluble P-selectin were also measured simultaneously by flow
      cytometry. RESULTS: Patients with ACS exhibited higher level of PMAs compared
      with SAP patients and the control. Furthermore, the levels of IL-6, IL-8, MCP-1,
      soluble CD40L, soluble P-selectin and CRP were also significantly higher in ACS
      patients than in SAP patients and the control group. However, there were no
      significant difference in the levels of IL-8, sCD40L, sP-selectin and CRP between
      SAP patients and the control group. Correlation analysis showed that high levels
      of IL-6 and sP-selectin were significantly correlated with PMAs. Logistic
      analysis further demonstrated that the presence of elevated CRP, IL-6 and PMAs
      level each confers an increased risk of ACS. CONCLUSION: Elevated levels of PMAs
      and related circulating biomarkers might indicate the unstable coronary syndrome
      in ACS patients, and the levels of PMAs, CRP and IL-6 could be used for
      monitoring and guiding the early intervention of ACS patients.

PMID- 16887213
TI  - A cross-sectional study of hypertension in an elderly population (75 years and
      over) with atrial fibrillation: secondary analysis of data from the Birmingham
      Atrial Fibrillation in the Aged (BAFTA) randomised controlled trial.
AB  - BACKGROUND: Atrial fibrillation and hypertension are two common conditions in the
      elderly, associated with significant morbidity and mortality. Little information
      is available regarding the epidemiology of hypertension in elderly patients with
      atrial fibrillation. SUBJECTS AND METHODS: A secondary analysis of data from the
      Birmingham Atrial Fibrillation Treatment of the Aged study, a randomised
      controlled trial of thrombo-prophylaxis in atrial fibrillation in a primary care
      population. The study population comprised patients aged 75 and over with
      electrocardiogram (ECG) confirmed atrial fibrillation. Blood pressure was
      recorded in the general practice surgery on two occasions using standardised
      methods. History of hypertension was sought from the medical records and from
      asking the patient. RESULTS: 3059 subjects had ECG confirmed atrial fibrillation.
      The prevalence of a history of hypertension in this group was 57.5%. The mean
      systolic blood pressure was 141 mmHg (standard deviation: 21 mmHg) in men and 144
      mmHg (22 mmHg) in women. The mean diastolic blood pressure was 79 mmHg (12 mmHg)
      in men and 80 mmHg in women (12 mmHg). The mean systolic blood pressure was
      slightly lower than that of the general population aged 75 and over, but the mean
      diastolic blood pressure was significantly higher in patients in atrial
      fibrillation (by 8 mmHg). Among the patients with a diagnosis of hypertension,
      86.5% were on blood pressure lowering medications. CONCLUSIONS: Hypertension is
      more commonly diagnosed in older patients with atrial fibrillation than in the
      general population. The mean systolic blood pressure is slightly lower, but the
      mean diastolic blood pressure substantially higher in older patients in atrial
      fibrillation, compared to the general population.

PMID- 16887215
TI  - Effects of prolonged metoprolol treatment on neural remodeling and inducible
      ventricular arrhythmias after myocardial infarction in rabbits.
AB  - BACKGROUND: Neural remodeling is part of the pathophysiology of ventricular
      arrhythmias after myocardial infarction (MI). In this study, we developed a
      rabbit model of MI to investigate the effect of the beta-blocker metoprolol on
      ventricular neural remodeling and susceptibility to ventricular arrhythmias.
      METHODS: MI was induced by ligation of the left anterior descending coronary
      artery in 30 rabbits, and sham operations were performed in 12 control animals.
      Metoprolol was then administered to 15 of the MI animals. After
      electrophysiological recordings, the expression of nerve markers was studied at
      the infarct border and the non-infarct left ventricle free wall (LVFW) by
      immunostaining or RT-PCR. RESULTS: Eight weeks after MI, the incidence of
      inducible ventricular arrhythmias was significantly (P<0.01) higher in the MI
      group than in the sham group. However, metoprolol treatment decreased incidence
      of post-MI ventricular arrhythmias (8.3%) compared to those without treatment
      (58.3%, P<0.001). The density of nerve fibers was increased in MI group (3889+/
      521 microm(2)/mm(2)) compared to the sham group (1727+/-304 microm(2)/mm(2)).
      Treatment of MI rabbits with metoprolol resulted in a partial reduction (2725+/
      283 microm(2)/mm(2)). However, the shape and imbalance of nerve fibers appeared
      to be normalized by the metoprolol treatment. The expression levels of TH mRNA
      were reduced (P<0.01) by metoprolol treatment. CONCLUSION: Metoprolol reduces
      post-MI ventricular arrhythmias, partly by altering the neural remodeling
      process.

PMID- 16887216
TI  - Urotensin II is raised in acute myocardial infarction and low levels predict risk
      of adverse clinical outcome in humans.
AB  - BACKGROUND: UII is elevated in patients with heart failure; however its role in
      acute myocardial infarction (AMI) is unknown. We sought to compare levels of UII
      in patients with AMI to controls. We also compared UII to N terminal pro B type
      natriuretic peptide (NT-BNP) to evaluate whether levels of UII can be used to
      predict the risk of adverse clinical outcome (ACO). METHODS AND RESULTS: 129
      patients were studied with serial blood measurements and echocardiogram during
      their index admission. Plasma concentration of median UII was significantly
      elevated in AMI compared to controls (median 1.40 vs. 0.42 fmol/ml p<0.012). Over
      the median follow up of 102 days (range 0-189) there were 14 deaths and 14
      readmissions with AMI or heart failure. Using a Cox proportional hazards model
      the only independent predictors of ACO were UII (OR 0.29, p=0.046) and NT-BNP (OR
      4.78, p=0.012) between 73 and 96 h. The Kaplan-Meier survival curve revealed a
      significantly better clinical outcome in patients with UII above the median
      compared with UII below the median. CONCLUSIONS: UII levels are raised in AMI and
      is an independent predictor of ACO. Patients with a poor outcome mount a lower
      UII response suggesting a possible cardioprotective role for this peptide.

PMID- 16887217
TI  - Acute coronary syndrome associated with myocardial bridging due to ergotamine
      treatment for migraine.
AB  - A 48-year-old woman presented with acute coronary syndrome and underwent coronary
      angiography which revealed myocardial bridging at the distal end of the left
      anterior descending artery with otherwise normal coronary arteries. The patient
      used to take ergotamine for her chronic migraine. Possible association with
      myocardial bridging which was found in this patient is discussed.

PMID- 16887218
TI  - Intracoronary air embolism in open heart surgery--an uncommon source of
      myocardial ischaemia.
AB  - We report a case of air embolism detected by transesophageal echocardiography in
      a patient undergoing open heart surgery for acute mitral regurgitation.
      Intraoperative transesophageal echocardiography revealed an increased brightness
      of the apical wall and a severely compromised left ventricular myocardium with
      severe diffuse hypokinesis after removal of the aortic cross clamps and
      spontaneous resolution in the control echocardiography.

PMID- 16887219
TI  - Left coronary artery-to-left ventricular fistula. A follow-up report.

PMID- 16887220
TI  - Macroscopic assessment of porcine coronary vessel wall trauma after percutaneous
      cardiac catheterization and intervention.
AB  - A macroscopic pathological assessment of the coronary arteries of a pig's heart,
      in which stent implantation and intra-vascular ultrasound and thermography
      pullbacks were performed, shows that during percutaneous coronary catheterization
      and intervention, one of the major vessel traumas occurs in the very proximal
      part of the coronary arteries, where the guiding catheter tip is manipulated to
      adequately engage the vessels.

PMID- 16887221
TI  - Large patent ductus arteriosus closure with multiple controlled-release coils.

PMID- 16887222
TI  - Risk factors for unsuccessful dog ownership: an epidemiologic study in Taiwan.
AB  - This retrospective study of 259 Taiwanese dog owners in 2004 addressed one of the
      major contributors to dog overpopulation in Taiwan: unsuccessful dog ownership.
      We found an inverse association between age of the dog at acquisition and risk of
      unsuccessful dog ownership: the younger the dog at acquisition the higher the
      risk. The incidence-proportion ratios (IPRs) of unsuccessful dog ownership for
      the owners who had a history of pet abandonment or losing a pet compared with
      those without such a history were 1.8 (95% confidence interval (CI)=1.1, 3.0) and
      2.1 (95% CI=1.3, 3.3), respectively. Soiling (IPR=2.0, 95% CI=1.3, 3.1) and
      barking (IPR=1.6, 95% CI=1.0, 2.6) problems had the strongest effects on
      unsuccessful dog ownership among the post-acquisition variables studied.
      Preventing owners with a history of unsuccessful dog ownership from acquiring
      dogs was predicted to yield the largest reduction of risk of unsuccessful dog
      ownership among the investigated variables (population attributable fraction=33%,
      95% CI=11%, 50%).

PMID- 16887223
TI  - Evaluation of a contract breeding management program in selected Ohio dairy herds
      with event-time analysis I. Cox proportional hazards models.
AB  - An observational study was conducted in order to assess the impact of a contract
      breeding program on the reproductive performance in a selected group of Ohio
      dairies using event-time analysis. The contract breeding program was offered by a
      breeding co-operative and featured tail chalking and daily evaluation of cows for
      insemination by co-operative technicians. Dairy employees no longer handled
      estrus detection activities. Between early 2002 and mid-2004, test-day records
      related to production and reproduction were obtained for 16,453 lactations
      representing 11,398 cows in a non-random sample of 31 dairies identified as well
      managed client herds of the breeding co-operative. Of the 31 herds, 15 were using
      the contract breeding at the start of the data acquisition period, having started
      in the previous 2 years. The remaining 16 herds managed their own breeding
      program and used the co-operative for semen purchase. Cox proportional hazards
      modeling techniques were used to estimate the association of the contract
      breeding, as well as the effect of other significant predictors, with the hazard
      of pregnancy. Two separate Cox models were developed and compared: one that only
      considered fixed covariates and a second that included both fixed and time
      varying covariates. Estimates of effects were expressed as the hazard ratio (HR)
      for pregnancy. Results of the fixed covariates model indicated that, controlling
      for breed, herd size, use of ovulation synchronization protocols in the herd,
      whether somatic cell score exceeded 4.5 prior to pregnancy or censoring, parity,
      calving season, and maximum test-day milk prior to pregnancy or censoring, the
      contract breeding program was associated with an increased hazard of pregnancy
      (HR=1.315; 95% CI 1.261-1.371). The results of the time-varying covariates model,
      which controlled for breed, herd size, use of ovulation synchronization
      protocols, somatic cell score above 4.5, parity, calving season, and testing
      season also found that the program was associated with an increased hazard of
      pregnancy (HR=1.387; 95% CI 1.327-1.451). The fixed and time-varying covariates
      models both found similar sets of predictors when analyzing the association of
      the contract breeding program with hazard of pregnancy. Both models identified a
      30% or greater increase in hazard of pregnancy associated with use of the
      contract breeding program, suggesting that herds subscribing to the program
      achieved pregnancies in a more timely fashion.

PMID- 16887224
TI  - Combined sigB allelic typing and multiplex PCR provide improved discriminatory
      power and reliability for Listeria monocytogenes molecular serotyping.
AB  - Conventional serotyping has traditionally been used to subtype Listeria
      monocytogenes, but has several limitations, including low discriminatory power
      and poor reproducibility. Molecular serotyping methods have been developed for L.
      monocytogenes, but generally show limited discriminatory power and high
      misclassification rates. We selected 157 Listeria isolates to evaluate a
      combination of a previously described multiplex PCR assay and sigB allelic typing
      as an alternative molecular serotyping and subtyping strategy for L.
      monocytogenes. While the multiplex PCR assay differentiated five L. monocytogenes
      subtypes (Simpson's Index of Discrimination [SID]=0.78), including classification
      of the most common disease-associated serotypes (1/2a, 1/2b, 1/2c, and lineage I
      4b) into four distinct groups, it misclassified 3.8% of the isolates studied
      here. sigB allelic typing differentiated 29 subtypes (SID=0.87) and also allowed
      identification of lineage III L. monocytogenes, which could not be differentiated
      from the other Listeria spp. by the multiplex PCR assay. sigB allelic typing
      failed to differentiate serotype 1/2c and 1/2a isolates and one sigB allelic type
      included serotype 4b and 1/2b isolates. A molecular serotyping approach that
      combines multiplex PCR and sigB sequence data showed increased discriminatory
      power (SID=0.91) over either method alone as well as conventional serotyping
      (SID=0.87) and classifies the four major serotypes (i.e., 1/2a, 1/2b, 1/2c, and
      4b) into unique subgroups with a lower misclassification rate as compared to the
      multiplex PCR assay. This combined approach also differentiates lineage I
      serotype 4b isolates from the genetically distinct serotype 4b isolates
      classified into lineage III.

PMID- 16887225
TI  - A novel fluorescence imaging technique combining deconvolution microscopy and
      spectral analysis for quantitative detection of opportunistic pathogens.
AB  - A novel fluorescence imaging technique based on deconvolution microscopy and
      spectral analysis is presented here as an alternative to confocal laser scanning
      microscopy. It allowed rapid, specific and simultaneous identification of five
      major opportunistic pathogens, relevant for public health, in suspension and
      provided quantitative results.

PMID- 16887226
TI  - SCAR-based real time PCR to identify a biocontrol strain (T1) of Trichoderma
      atroviride and study its population dynamics in soils.
AB  - Strains of Trichoderma spp. are known for their antagonistic properties against
      plant pathogens, some are already on the market, others are under development. In
      order to launch a strain on the market its perfect identification at the species
      and strain levels is needed. The aim of this study is to (i) design a SCAR marker
      for specific identification of strain T1 of Trichoderma atroviride and (ii)
      monitor population dynamics of this strain in soil by real time PCR. A primer
      pair targeting a 141-bp fragment enabled specific detection of this strain
      without cross detection of autochthonous populations of Trichoderma in several
      field soils. In two soils, population dynamics assessed by real time PCR and the
      soil plate technique gave similar results. The molecular tools developed in this
      study satisfy the requirement for specific identification of the biocontrol
      strain and for detection and quantification of T. atroviride T1 population in
      complex environments.

PMID- 16887227
TI  - Evoked gamma band response in male adolescent subjects at high risk for
      alcoholism during a visual oddball task.
AB  - This study investigates early evoked gamma band activity in male adolescent
      subjects at high risk for alcoholism (HR; n=68) and normal controls (LR; n=27)
      during a visual oddball task. A time-frequency representation method was applied
      to EEG data in order to obtain stimulus related early evoked (phase-locked) gamma
      band activity (29-45 Hz) and was analyzed within a 0-150 ms time window range.
      Significant reduction of the early evoked gamma band response in the frontal and
      parietal regions during target stimulus processing was observed in HR subjects
      compared to LR subjects. Additionally, the HR group showed less differentiation
      between target and non-target stimuli in both frontal and parietal regions
      compared to the LR group, indicating difficulty in early stimulus processing,
      probably due to a dysfunctional frontoparietal attentional network. The results
      indicate that the deficient early evoked gamma band response may precede the
      development of alcoholism and could be a potential endophenotypic marker of
      alcoholism risk.

PMID- 16887228
TI  - Supplementation of the cultivation media with B-group vitamins enhances
      lovastatin biosynthesis by Aspergillus terreus.
AB  - The impact of the supplementation of cultivation media with B-group vitamins on
      the biosynthesis of lovastatin (mevinolinic acid) by Aspergillus terreus
      ATCC20542 was investigated. A hypothesis was formulated that as the biosynthesis
      of lovastatin requires a high throughput of coenzymes in the cells, the
      application of its precursors in the form of B-group vitamins might positively
      influence the process. In a nitrogen-deficient medium the B-group vitamins, both
      single, especially nicotinamide, pyridoxine and calcium D-pantothenate, and a
      mixture of thiamine, riboflavin, pyridoxine, calcium d-pantothenate and
      nicotinamide increased the efficiency of lovastatin biosynthesis. The vitamin
      supplementation also increased both volumetric and specific production rates of
      mevinolinic acid, especially before 80 h of the process, when no lactose
      limitation had been observed yet.

PMID- 16887229
TI  - Deformable gas-filled microbubbles targeted to P-selectin.
AB  - Ultrasound contrast microbubbles have been successfully targeted to a number of
      intravascular disease markers. We hypothesized that targeted delivery could be
      improved further, by making the microbubbles deformable, leading to increased
      microbubble-endothelium adhesion contact area and stabilized adhesion. Activated
      leukocytes utilize such strategy; they deform after binding to inflamed
      endothelium in the vasculature. Lipid-shell microbubbles were targeted to the
      endothelial inflammatory protein P-selectin with a monoclonal anti-P-selectin
      antibody attached to the microbubble shell. Deformable microbubbles were created
      by controlled pressurization with partial gas loss, which generated an average
      excess shell surface area of approximately 30% and the formation of outward
      projected wrinkles and folds. Targeted microbubble adhesion and deformability
      were assessed in the parallel plate flow chamber under shear flow. Sustained
      adhesion of deformable microbubbles at wall shear stresses between 0.4 and 1.35
      dyn/cm(2) was consistently better than adhesion of wrinkle-free microbubbles.
      Over this shear range, targeted wrinkled microbubbles were deformed by shear
      flow, unlike wrinkle-free microbubbles. In a murine cremaster inflammation model,
      a significant improvement of deformable microbubble targeting was observed by
      intravital microscopy. Overall, the mechanical aspects of adhesion, such as
      particle shape, deformability and surface microstructure, are important in
      engineering efficient site-targeted particle-based agents for medical imaging and
      therapy.

PMID- 16887230
TI  - DNA/cationic polymer complex attachment on a human vascular endothelial cell
      monolayer exposed to a steady laminar flow.
AB  - This study evaluated for the first time the binding of pDNA/polymer complexes
      (polyplexes) on a human lung microvascular endothelial cell (HLMEC) monolayer
      under flow conditions. A slide of a HLMEC monolayer was mounted on a parallel
      flow chamber connected to an open flow system from a reservoir containing
      fluorescent polyplexes to a syringe. A precise pump allowed their passage through
      the chamber under a range of shear stresses. The binding of polyethyleneimine
      (PEI)- and histidylated polylysine (His)-polyplexes was carried out over 30 min
      by time-lapse video microscopy. At 10 microg pDNA/ml in 10% serum, we found that
      360+/-80 PEI- and 250+/-50 His-polyplexes were bound per 1000 cells at a shear
      stress of 0.3-1 dyn/cm(2). This number dropped to approximately 100 at 2
      dyn/cm(2). These polyplexes exhibited differences in their interactions with the
      cell membrane. Concerning PEI-polyplexes, there was a shear threshold effect
      allowing a maximum binding at 0.06 dyn/cm(2) and a higher binding reduction (77%)
      at 5 microg/ml pDNA in 100% serum. The polyplex binding was augmented by 300%
      with PEI bearing tetraglucose moiety. This set-up is potentially helpful to
      screen a wide array of endothelial cells ligands prior in vivo experiments.

PMID- 16887232
TI  - Angiographic coronary artery disease is associated with progressively higher
      levels of fasting plasma glucose.
AB  - This study evaluated the association between progressively higher levels of
      fasting glycemia (G) and insulin resistance parameters with coronary artery
      disease (CAD) in patients referred for coronary angiography. All 145 patients
      (age 58.4+/-0.9 years, 51.7% men) underwent clinical and laboratory evaluation
      before coronary angiography and subjects were divided into four groups: normal
      (N, <88 mg/dl), high-normal (H-N, 89-99 mg/dl), impaired fasting glucose (IFG,
      100-125 mg/dl) and diabetes (DM, >126 mg/dl or known diabetics). Arteriographic
      evidence of CAD was determined by two criteria: (1) a 30% or greater diameter
      stenosis in at least one major coronary artery; (2) a 70% or greater diameter
      stenosis in at least one major coronary artery. HOMA-IR increased progressively
      according to each group: N=1.74+/-0.2, H-N=3.14+/-0.3, IFG=4.67+/-0.6 and
      DM=8.00+/-2.9; p=0.001. The proportion of patients with CAD according to both
      criteria increased with each G level: CAD criteria 1: N=39.4%, H-N=50%, IFG=60%
      and DM=69.6%, p=0.006; CAD criteria 2: N=27.3%, H-N=30%, IFG=36% and DM=50%,
      p=0.03. We demonstrated a significant association between subtle disturbances of
      the glucose metabolism, assessed by subnormal levels of fasting glucose and
      insulin resistance parameters, and angiographically documented coronary artery
      disease.

PMID- 16887233
TI  - Prognostic role of K-Ras mutations in non-small cell lung cancer: still an issue
      for open debate.
AB  - We herein comment on a recently published experience on circulating K-ras DNA in
      lung cancer patients.

PMID- 16887234
TI  - Early legume responses to inoculation with Rhizobium sp. NGR234.
AB  - Interactions between legumes and rhizobia are controlled by the sequential
      exchange of symbiotic signals. Two different techniques, 2D-PAGE electrophoresis
      and differential display were used to study the effects of rhizobial signals on
      legume development. Application of variously substituted lipo-oligo-saccharidic
      Nod-factors to roots of Vigna unguiculata resulted in changes in the
      phosphorylation patterns of microsomal proteins. Reliable amino-acid sequences
      were obtained for one Nod-factor enhanced protein which was highly homologous to
      the 57-kDa subunit from Arabidopsis thaliana vacuolar membrane H(+)-ATPase.
      Immuno-blotting techniques demonstrated that Nod-factors cause rapid and massive
      increases of this enzyme in treated roots, suggesting that H(+)-ATPases play
      symbiotic roles. Concomitantly, we used differential display (DD) techniques on
      mRNA isolated from root-hairs to analyse early root responses to NGR234.
      Significant matches of several DD clones to known sequences were found. Clone
      D2.62 was homologous to a multitude of receptor kinases including S receptor-like
      kinases of A. thaliana and clone D4.1 showed similarities to Lotus japonicus
      phosphatidylinositol transfer-like protein III and late nodulin 16. Independent
      confirmatory analyses of these differentially expressed clones indicated
      expression at very low levels.

PMID- 16887235
TI  - Biosynthesis of malonylated flavonoid glycosides on the basis of
      malonyltransferase activity in the petals of Clitoria ternatea.
AB  - The crude malonyltransferase from the petals of Clitoria ternatea was
      characterized enzymatically to investigate its role on the biosynthetic pathways
      of anthocyanins and flavonol glycosides. In C. ternatea, a blue flower cultivars
      (DB) and mauve flower variety (WM) accumulate polyacylated anthocyanins
      (ternatins) and delphinidin 3-O-(6''-O-malonyl)-beta-glucoside which is one of
      the precursors of ternatins, respectively. Moreover, WM accumulates minor
      delphinidin glycosides - 3-O-beta-glucoside, 3-O-(2''-O-alpha-rhamnosyl)-beta
      glucoside, 3-O-(2''-O-alpha-rhamnosyl-6''-O-malonyl)-beta-glucoside of
      delphinidin. These glycosidic patterns for minor anthocyanins in WM are also
      found among the minor flavonol glycosides in all the varieties including a white
      flower variety (WW) although the major flavonol glycosides are 3-O-(2''-O-alpha
      rhamnosyl)-beta-glucoside, 3-O-(6''-O-alpha-rhamnosyl)-beta-glucoside, 3-O
      (2'',6''-di-O-alpha-rhamnosyl)-beta-glucoside of kaempferol, quercetin, and
      myricetin. How do the enzymatic characteristics affect the variety of glycosidic
      patterns in the flavonoid glycoside biosynthesis among these varieties? While the
      enzyme from DB highly preferred delphinidin 3-O-beta-glucoside in the presence of
      malonyl-CoA, it also has a preference for other anthocyanidin 3-O-beta
      glucosides. It could use flavonol 3-O-beta-glucosides in much lower specific
      activities than anthocyanins; however, it could not utilize 3-O-(2''-O-alpha
      rhamnosyl)-beta-glucosides of anthocyanins and flavonols, and 3,3'-di- and
      3,3',5'-tri-O-beta-glucoside of delphinidin - other possible precursors in
      ternatins biosynthesis. It highly preferred malonyl-CoA as an acyl donor in the
      presence of delphinidin 3-O-beta-glucoside. The crude enzymes prepared from WM
      and WW had the same enzymatic characteristics. These results suggested that 3-O
      (2''-O-alpha-rhamnosyl-6''-O-malonyl)-beta-glucosides of flavonoids were
      synthesized via 3-O-(6''-O-malonyl)-beta-glucosides rather than via 3-O-(2''-O
      alpha-rhamnosyl)-beta-glucosides, and that malonylation proceeded prior to
      glucosylation at the B-ring of delphinidin in the early biosynthetic steps
      towards ternatins. It seemed that the substrate specificities largely affected
      the difference in the accumulated amount of malonylated glycosides between
      anthocyanins and flavonols although they are not simply proportional to the
      accumulation ratio. This enzyme might join in the production of both
      malonylanthocyanins and flavonol malonylglycosides as a result of broad substrate
      specificities towards flavonoid 3-O-beta-glucosides.

PMID- 16887236
TI  - Involvement of neurotensin in cancer growth: evidence, mechanisms and development
      of diagnostic tools.
AB  - Focusing on the literature of the past 15 years, we evaluate the evidence that
      neurotensin and neurotensin receptors participate in cancer growth and we
      describe possible mechanisms. In addition, we review the progress achieved in the
      use of neurotensin analogs to image tumors in animals and humans. These exciting
      advances encourage us to pursue further research and stimulate us to consider
      novel ideas regarding the multiple inputs to cancer growth that neurotensin might
      influence.

PMID- 16887237
TI  - Expression and p75 neurotrophin receptor dependence of cholesterol synthetic
      enzymes in adult mouse brain.
AB  - Normal brain function depends critically on cholesterol. Although cholesterol is
      synthesized locally in the adult brain, the precise anatomical localization of
      cholesterogenic enzymes is not known. Here we show that 3-hydroxy-3
      methylglutaryl-coenzyme A reductase (HMG-CoAred) and 7-dehydrocholesterol
      reductase (7dhcred), the first and last enzymes, respectively, in the cholesterol
      biosynthesis pathway, are co-expressed in neurons throughout adult murine brain.
      Co-localization is most prominent in cortical, hippocampal, and cholinergic
      neurons. Since adult hippocampal and cholinergic neurons express p75 neurotrophin
      receptors (p75NTR) we hypothesized that p75NTR regulates expression of
      cholesterogenic enzymes. Treatment of Neuro2a neuroblastoma cells or primary
      cerebellar cultures with siRNA downregulates p75NTR and decreases the expression
      level of HMG-CoAred and 7dhcred. Native neuroblastoma cell lines with
      differential expression of p75NTR differentially express 7dhcred; 7dhcred
      expression correlates with p75NTR expression. This suggests that, in p75NTR
      expressing cells, p75NTR regulates cholesterol synthesis through regulation of
      HMG-CoAred and 7dhcred expression. The unexpected localization of cholesterogenic
      enzymes in adult neurons suggests that at least some adult neurons retain the
      ability to synthesize cholesterol.

PMID- 16887238
TI  - Exploring factors affecting attrition of male students from an undergraduate
      nursing course: a qualitative study.
AB  - This article reports the findings of a qualitative study that investigated the
      factors influencing both the academic and clinical practice performance of
      undergraduate male nursing students at a regional Australian university. The
      impetus for the study evolved from the recognition that, despite increasing
      numbers of males choosing to undertake nursing as a career, attrition by males
      from nursing courses continues to be problematic. In a profession that is
      hallmarked by critical staff shortages, it was viewed as important to investigate
      reasons contributing to the attrition of male nursing students enrolled in
      undergraduate nursing courses. The informants for the research were eight male
      nursing students enrolled internally in the Bachelor of Nursing course at a
      regional university in Australia. Data were collected using in-depth interviews
      and written narratives in the form of a diary. Data were analysed using thematic
      analysis, the findings revealing that male nursing students face particular
      challenges from an academic and clinical practice perspective during their
      university experience. For example, themes identified from interviews and
      narratives highlighted the fact that there is a tendency for male nursing
      students to feel isolated and excluded from an academic and clinical perspective.
      As well as this, the informants in this study clearly highlighted their
      preference for engaging in the technical aspects of nursing. The implications for
      nurse educators are emphasized and from this, educational strategies are
      suggested to facilitate the retention of male nursing students in undergraduate
      nursing courses.

PMID- 16887239
TI  - Recombinant vaccines based on translocated effector proteins of Salmonella
      Pathogenicity Island 2.
AB  - Attenuated live Salmonella enterica are useful carriers for the delivery of
      heterologous antigens for vaccination. Effector proteins translocated by type III
      secretion systems (T3SS) of Salmonella have been successfully utilized for
      antigen delivery. Here we investigated the use of effector proteins of the T3SS
      encoded by Salmonella Pathogenicity Island 2 (SPI2). We observed that the
      effector protein SseF is suitable for delivery of various fusion proteins with
      heterologous antigens. The efficiency of this carrier protein was demonstrated in
      vaccination experiments with fusion proteins with Listeria monocytogenes
      protective antigens. SseF can thus be used as a versatile vehicle for
      translocation of heterologous proteins for vaccination.

PMID- 16887240
TI  - Immunologic synergism with IL-2 and effects of cCHMIs on mRNA expression of IL-2
      and IFN-gamma in chicken peripheral T lymphocyte.
AB  - Two compound Chinese herbal medicinal ingredients (cCHMIs) were prepared,
      respectively, with epimedium polysaccharide plus propolis flavone (cCHMIs 1) and
      astragalus polysaccharide plus ginsenoside (cCHMIs 2). In animal immune
      experiment, Newcastle disease vaccine was mixed, respectively, with two cCHMIs
      and IL-2 to vaccinate 15-day-old chicken in experimental groups. On days 7, 14,
      21 and 28 after vaccination, the dynamic changes of serum antibody titers were
      tested by micro-method. In gene expression experiment, each cCHMIs, at three
      concentrations, was added into cultured chicken peripheral T lymphocyte. After
      cultivation of 7h, the expression of IL-2 mRNA in the cell, 24h, IFN-gamma mRNA,
      were determined by semi-quantitative RT-PCR assay. The results showed that two
      cCHMIs, whether single or cooperative injection with IL-2, could significantly
      raise the antibody titers, while immunologic synergisms of two cCHMIs with IL-2
      were unconspicuous. cCHMs 1 at three doses and cCHMIs 2 at high dose could
      remarkably promote the expression of IL-2 mRNA in chicken T lymphocyte, two
      cCHMIs at three doses, the expression of IFN-gamma mRNA, which could explain why
      the immunologic synergism of cCHMIs with IL-2 was not obvious.

PMID- 16887241
TI  - Studies on immunogenicity and protective efficacy of DnaJ of Salmonella Typhi
      against lethal infection by Salmonella Typhimurium in mice.
AB  - In the present study DnaJ (HSP40) of Salmonella enterica serovar Typhi has been
      evaluated for its immunogenicity and efficacy in protecting mice against lethal
      challenge by S. enterica serovar Typhimurium infection. DnaJ was amplified by PCR
      of the genomic DNA of S. Typhi and subsequently cloned in pQE-30 expression
      vector. The protein was induced by IPTG and purified using Ni-NTA chromatography
      under denaturing conditions. After refolding in vitro the immune response was
      evaluated by injecting 40 microg DnaJ protein/mouse i.p. on 0th, 7th and 28th
      day. The results showed a significant increase in antibody titre and lymphocyte
      proliferation in animals immunised with DnaJ as compared to control. Further
      there was an appreciable increase in IL-2, IL-4, IFN-gamma production in
      lymphocytes isolated from immunised mice as compared to control. In this limited
      study, immunisation of mice with DnaJ was found to provide 70% protection against
      lethal challenge by S. Typhimurium indicating the possible use of DnaJ as vaccine
      candidate against typhoid.

PMID- 16887242
TI  - Adjuvant activity of Quillaja brasiliensis saponins on the immune responses to
      bovine herpesvirus type 1 in mice.
AB  - The chemical characterization of aqueous extracts (AE) of barks, leaves and
      branches and the saponin fraction denominated QB-90 obtained from Quillaja
      brasiliensis, a native species from Southern Brazil, show remarkable similarities
      to Quillaja saponaria saponins which are known as adjuvants in vaccine
      formulations. In vivo toxicity assays of AE and QB-90 showed not to be lethal for
      mice in doses ranging from 50 to 1600 microg and 50-400 microg, respectively.
      Experimental vaccines prepared with bovine herpesvirus type 1 (BHV-1) antigen and
      either AE (barks 100 microg, leaves 400 microg, branches 400 microg) or QB-90
      (100 microg) were able to enhance the immune responses of mice in a comparable
      manner to saponins from Q. saponaria (QuilA, 100 microg). BHV-1 specific IgG,
      IgG1 and IgG2a antibody levels in serum were also significantly enhanced by AE,
      QB-90 and QuilA compared to control group (p<0.05). These results showed that AE
      and QB-90 from Q. brasiliensis are potential candidates as adjuvants in vaccines.

PMID- 16887243
TI  - The investigation of 137Cs and 90Sr background radiation levels in soil and plant
      around Tianwan NPP, China.
AB  - (137)Cs and (90)Sr background levels in soil and plant around Tianwan Nuclear
      Power Plant (NPP) are reported. Eighty-four soil samples and 44 plant samples
      were collected from March 2000 to April 2002. The samples were analyzed by gamma
      spectrometry and radiochemical separation procedure to quantify (137)Cs and
      (90)Sr radioactivities. The concentrations (Bqkg(-1) dry weight) have been
      observed in the range of 0.6-1.6 for (90)Sr and 1.4-6.9 for (137)Cs in soils,
      their average values are 1.0+/-0.3 and 4.6+/-1.6, respectively, which are
      relatively lower than the reported values in neighboring countries. The mean
      concentrations (in Bqkg(-1) fresh weight except for tea and grass which is
      expressed in Bqkg(-1) dry weight) of (137)Cs and (90)Sr are 0.1+/-0.03 and 7.7+/
      4.1 in pine needle, 0.27+/-0.05 and 3.0+/-1.1 in tea, 0.65+/-0.19 and 2.1+/-0.3
      in grass, 0.033+/-0.021 and 0.084+/-0.045 in wheat, 0.019+/-0.01 and 0.23+/-0.06
      in China cabbage, and 0.009+/-0.007 and 0.024+/-0.084 in rice, respectively. The
      pine needle and tea can be regarded as indicator species for (90)Sr and (137)Cs.
      The soil-to-plant transfer factor (TF) values of (90)Sr and (137)Cs are,
      respectively, 0.022 and 0.031 for rice, 0.066 and 3.83 for China cabbage, 0.0088
      and 0.089 for wheat, and 0.037 and 0.56 for grass.

PMID- 16887244
TI  - Biogeochemical signatures in the lichen Hypogymnia physodes in the mid Urals.
AB  - Multi-element content and uranium (U) isotopes were investigated in the lichen
      Hypogymnia physodes (native and transplants) sampled across a 60-km transect,
      centred on Karabash smelter town, from Turgoyak Lake (SW) to Kyshtym (NE) to
      investigate the origin of U. Kyshtym was the site of a major nuclear accident in
      1957. (234)U/(238)U activity ratios in native thalli sampled during July 2001
      were within the natural isotopic ratio in minerals. Uranium/thorium (U/Th) ratios
      were higher in native thalli towards the NE (average 0.73) than those in the SW
      (average 0.57). Element signatures in native thalli and transplants suggest U was
      derived from fossil fuel combustion from Karabash and sources lying further to
      the east. Systematic and significant U enrichment indicative of a nuclear fuel
      cycle source was not detected in any sample. Element signatures in epiphytic
      lichen transplants and native thalli provide a powerful method to evaluate U
      deposition.

PMID- 16887245
TI  - Outpatient process quality evaluation and the Hawthorne Effect.
AB  - We examine the evidence that the behavior of clinicians is impacted by the fact
      that they are being observed by a research team. Data on the quality of care
      provided by clinicians in Arusha region of Tanzania show a marked fall in quality
      over time as new patients are consulted. By conducting detailed interviews with
      patients who consulted both before and after our research team arrived we are
      able to show strong evidence of the Hawthorne effect. Patient-reported quality is
      steady before we arrive, rises significantly (by 13 percentage points) at the
      moment we arrive and then falls steadily thereafter. We show that quality after
      we arrive begins to look similar to quality before we arrived between the 10th
      and 15th consultations. Implications for quality measurement and policy are
      discussed.

PMID- 16887246
TI  - Psychological distress, gender, and health lifestyles in Belarus, Kazakhstan,
      Russia, and Ukraine.
AB  - This paper examines the relationship between psychological distress, gender, and
      health lifestyles in Belarus, Kazakhstan, Russia, and Ukraine. These countries
      have been subjected to highly stressful and extensive social change associated
      with the transition out of communism. Data were collected by face-to-face
      interviews (n = 10,406) in November 2001. Distress was measured by 12
      psychological distress symptoms. Health lifestyles focused on measures of alcohol
      consumption, smoking and diet. We found that females carried a much heavier
      burden of psychological distress than males, but this distress did not translate
      into greater alcohol consumption and smoking for these women or for men. The
      greatest influence of distress on health lifestyle practices was on daily diets
      in that both less distressed females and males consumed a more balanced diet than
      more distressed persons. Our findings suggest that it is the normative demands of
      a particular lifestyle, rather than distress, that principally shapes the pattern
      of heavy male drinking. This is an important finding as some sources indicate
      heavy drinking is largely responsible for the health crisis in the former
      socialist states.

PMID- 16887247
TI  - Primary caregivers of cancer patients in the palliative phase: a path analysis of
      variables influencing their burden.
AB  - Research has shown that several variables influence the burden of primary
      caregivers of cancer patients staying at home in the palliative phase, but the
      associations between these variables have hardly been explored. The aim of this
      study was to examine the associations of theory-driven variables with the
      caregivers' burden by means of path analysis. The sample consisted of 96
      caregivers of cancer patients in the palliative phase staying at home recruited
      from a hospital trust in Norway. The dimensions of burden from the Caregiver
      Reaction Assessment, namely self esteem, lack of family support, impact on
      finances, and impact on daily schedule, were used as the dependent variable. The
      following independent variables were tested in the models: the patients' levels
      of pain, fatigue, and nausea; and the caregivers' physical quality of life,
      anxiety and depression, and social support. The Partial Least Squares approach to
      structural equation modelling was used for the path analysis. Model 1 shows the
      direct associations between the independent variables and the dependent variable,
      explaining 16% of the variance in caregiver burden. Model 1 supports the finding
      that only caregivers' depression has a direct significant association with
      caregiver burden, and shows further that the effects of the other independent
      variables on burden are mediated through depression. In Model 2, anxiety and
      depression are mediating factors between three other independent variables and
      caregiver burden, and 12% of the variance is explained. Model 2 supports none of
      the independent variables as antecedents of burden. Testing of the models
      suggested that caregivers' depression was the main factor associated with
      caregiver burden, but also an important mediator of indirect associations of
      indirect associations of caregivers' anxiety and physical health.

PMID- 16887248
TI  - A qualitative analysis of a dyad approach to health-related quality of life
      measurement in children with asthma.
AB  - The measurement of health-related quality of life (HRQOL) in children often
      relies on parents as proxy respondents. Yet, several studies have shown poor to
      moderate correlations between parent and child responses, questioning the
      validity of the parent as proxy. This qualitative study examined a dyad approach,
      where parent and child were interviewed together. The objective was to observe
      and describe the interaction in a dyad interview, wherein both parent and child
      perspectives are used and where the parent may expand the child's cognitive
      abilities to create a more meaningful description of the child's HRQOL. Children
      aged 8-15 years with a clinical diagnosis of asthma and their primary caregivers
      were recruited from The Hospital for Sick Children, Toronto, Canada. The dyads
      were administered the Health Utilities Index Mark II/III, the Pediatric Asthma
      Quality of Life Questionnaire and the PedsQL Pediatric Quality of Life Inventory.
      Interviews were audio-taped and a second researcher recorded observations.
      Consistent with Grounded Theory methodology, observations were indexed according
      to categories and subcategories related to the response process. Data were
      analysed using open, axial and selective coding and constant comparison.
      Saturation was achieved at 16 dyad interviews. A cultural review and reflexive
      role taking were included to minimize interviewer bias and enhance rigour.
      Findings were grouped in the following 11 themes: recall difficulty, respondent
      bias, interviewer bias, frustration, coercion/parental influence, inter
      relational conflict, psychic discomfort for health states, emotional sensitivity,
      parent as advocate, parent as enabler and comprehension. The specification of
      these categories facilitated the creation of an interview guide to accompany the
      administration of standardized HRQOL questionnaires to parent-child dyads. Such a
      guide would facilitate discussion between parent and child and enhance the
      consistency of the interview process.

PMID- 16887249
TI  - The interpretation of "culture": diverging perspectives on medical provision in
      rural Montana.
AB  - Seeking to address evident disparities in health care delivery to minority
      populations, researchers have developed a framework generally referred to as
      "cultural competency." This framework suggests that increasing providers'
      knowledge about culturally specific beliefs and behaviors will both assist
      providers in caring for particular, traditionally underserved groups and enhance
      the quality of health care delivery for all patients. Meanwhile, a number of
      critics have challenged the presuppositions of the "culture" concept underlying
      cultural competency, arguing that such well-intended efforts may merely
      exacerbate received stereotypes. Despite such criticism, the influence of
      cultural competency, along with the related categories of cultural sensitivity,
      cultural humility, cultural proficiency, and cultural awareness, continues to
      grow in medical schools, governmental agencies, and health care organizations,
      particularly in the United States. To better assess the varying theoretical and
      policy claims of proponents and opponents of the cultural competency framework,
      we undertook a modest qualitative, interview-based investigation. We explored how
      "culture" is being presented and enacted by Mexican agricultural workers and US
      health care providers in one rural Montana clinic. While the Mexican agricultural
      workers in the study emphasized structural dimensions of labor migration as the
      most relevant factors in shaping patient-provider interactions, the US health
      care providers tended to focus on the "cultural characteristics" peculiar to
      their patients. The discrepancy in these assessments serves to extend and
      complement existing criticism of cultural competency. While our study was limited
      to one locale with a limited number of participants, its findings highlight the
      paucity of empirical research in this area and suggest the need to examine the
      efficacy of cultural competency in settings outside conventional "needs
      assessment" or "outcome studies" models.

PMID- 16887250
TI  - Perospirone in treatment of Huntington's disease: a first case report.
AB  - Huntington's disease (HD) is a hereditary disorder clinically characterized by
      involuntary movements, cognitive decline and psychiatric symptoms. We report on a
      patient with HD, whose involuntary movements and psychiatric symptoms were
      clinically improved with perospirone, a second-generation antipsychotic agent
      with antagonistic effects on serotonin 5-HT(2A) and dopamine D(2) (D(2))
      receptors, as well as a unique agonistic effect on serotonin 5-HT(1A) (5-HT(1A))
      receptors. The fact that perospirone antagonizes D(2) receptors could explain its
      effects on the hyperkinetic syndrome, while its agonistic effects on 5-HT(1A)
      receptors may explain the amelioration of psychiatric symptoms (fear and anxiety)
      in this patient. Future studies would be valuable to elucidate the utility of
      perospirone for the treatment of involuntary movements and psychiatric symptoms
      in HD.

PMID- 16887251
TI  - Approaches to the risk assessment of genotoxic carcinogens in food: a critical
      appraisal.
AB  - The present paper examines the particular difficulties presented by low levels of
      food-borne DNA-reactive genotoxic carcinogens, some of which may be difficult to
      eliminate completely from the diet, and proposes a structured approach for the
      evaluation of such compounds. While the ALARA approach is widely applicable to
      all substances in food that are both carcinogenic and genotoxic, it does not take
      carcinogenic potency into account and, therefore, does not permit prioritisation
      based on potential risk or concern. In the absence of carcinogenicity dose
      response data, an assessment based on comparison with an appropriate threshold of
      toxicological concern may be possible. When carcinogenicity data from animal
      bioassays are available, a useful analysis is achieved by the calculation of
      margins of exposure (MOEs), which can be used to compare animal potency data with
      human exposure scenarios. Two reference points on the dose-response relationship
      that can be used for MOE calculation were examined; the T25 value, which is
      derived from linear extrapolation, and the BMDL10, which is derived from
      mathematical modelling of the dose-response data. The above approaches were
      applied to selected food-borne genotoxic carcinogens. The proposed approach is
      applicable to all substances in food that are DNA-reactive genotoxic carcinogens
      and enables the formulation of appropriate semi-quantitative advice to risk
      managers.

PMID- 16887252
TI  - Baicalein attenuates methamphetamine-induced loss of dopamine transporter in
      mouse striatum.
AB  - Methamphetamine (METH) has been shown to cause dopaminergic neurotoxicity. By
      using the loss of dopamine transporter (DAT) as a marker of neurotoxicity, this
      study was aimed to investigate the neuroprotective effect of baicalein against
      METH-induced striatal damages in mice. Results from Western blotting showed that
      repeated METH administration (5 mg/kg, i.p., four injections at 2-h interval)
      caused 40% decrease of DAT level in mouse striatum measured at 72h after the last
      injection. Despite of the ineffectiveness at high dose (3.0 mg/kg, i.p.),
      pretreatment with lower doses of baicalein (0.3-1.0 mg/kg, i.p.) significantly
      attenuated the METH-induced striatal DAT loss in a dose-dependent manner.
      Furthermore, baicalein diminished METH-induced increase in striatal
      malondialdehyde content and myeloperoxidase activity, markers for lipid
      peroxidation and neutrophil increase, respectively. In addition, the present
      study also revealed that baicalein effectively diminished the ROS production by
      leukocytes stimulated with METH or PMA, a phorbol ester used as a positive
      control of stimulant. Surprisingly, we found that METH-induced nNOS
      overexpression was further increased by the pretreatment with baicalein while the
      level of nNOS was not altered significantly by baicalein treatment alone. These
      results suggested that baicalein may attenuate methamphetamine-induced DAT loss
      by inhibiting the neutrophil increase and the lipid peroxidation caused by
      neutrophil-derived reactive oxygen species in striatum.

PMID- 16887253
TI  - Glutathione peroxidase and glutathione reductase activities are partially
      responsible for determining the susceptibility of cells to oxidative stress.
AB  - Different cell types response differently to toxic insult. In a previous study,
      it was demonstrated that the C6 glioma cell is more sensitive to Cd induced
      oxidative stress than the HepG2 cells. To explain the difference between the two
      cell lines in their response to oxidative stress, it was hypothesized that the
      activity of glutathione metabolizing enzymes may be different. The objective of
      this study is to determine the activities of glutathione peroxidase (GPx) and
      glutathione reductase (GR) in the two cell lines and to explain how these
      differences may affect the susceptibility of the two cells to oxidative stress.
      In the HepG2 cells, the activity of GPx was 2.24+/-0.18 micromol/mg protein/min
      and that for GR was 5.63+/-0.58 micromol/mg protein/min. For the C6 glioma cells,
      GPx and GR activities were 1.29+/-0.14 and 1.07+/-0.11 micromol/mg protein/min,
      respectively. Using the kinetic equilibrium:
      K(eq)=([GSSG]x[NADPH]x[H(+)])/([GSH](2)x[NADP(+)]), and the GSH/GSSG previously
      published (HepG2: 2.6 and C6 glioma: 3.6), resting NADPH/NADP(+) for the cell
      lines were calculated. The results showed that NADPH/NADP(+) for HepG2 cells
      (17.8) is higher than that in the C6 glioma cells (10.8). These data supported
      the notion that the reducing power (NADPH/NADP(+)) in the HepG2 cells is higher
      than that in the C6 glioma cell and thus, the later would be more susceptible to
      oxidative stress. The results also suggested that besides GSH/GSSG, the
      activities of GPx and GR are important in predicting tissue redox state. Applying
      this hypothesis to animal tissues, the ratio of the activities of the two enzymes
      in mouse liver, cerebral cortex, hippocampus and cerebellum were measured. It was
      demonstrated that the activities of GPx and GR were different in the different
      tissues studied. The possible correlation between enzymatic activities and the
      redox state in the different tissues were discussed.

PMID- 16887254
TI  - Molecular packing in 1-hexanol-DMPC bilayers studied by molecular dynamics
      simulation.
AB  - The structure and molecular packing density of a "mismatched" solute, 1-hexanol,
      in lipid membranes of dimyristoyl phosphatidylcholine (DMPC) was studied by
      molecular dynamics simulations. We found that the average location and
      orientation of the hexanol molecules matched earlier experimental data on
      comparable systems. The local density or molecular packing in DMPC-hexanol was
      elucidated through the average Voronoi volumes of all heavy (non-hydrogen) atoms.
      Analogous analysis was conducted on trajectories from simulations of pure 1
      hexanol and pure (hydrated) DMPC bilayers. The results suggested a positive
      volume change, DeltaV(m), of 4 cm(3) mol(-1) hexanol partitioned at 310 K in good
      accordance with experimental values. Analysis of the apparent volumes of each
      component in the pure and mixed states further showed that DeltaV(m) reflects a
      balance between a substantial increase in the packing density of the alcohol upon
      partitioning and an even stronger loosening in the packing of the lipid.
      Furthermore, analysis of Voronoi volumes along the membrane normal identifies a
      distinctive depth dependence of the changes in molecular packing. The outer
      (interfacial) part of the lipid acyl chains (up to C8) is stretched by about 4%.
      Concomitantly, the average lateral area per chain decreases and these two effects
      compensate so that the overall packing density in the outer region, where the
      hexanol molecules are located, remains practically constant. The core of the
      bilayer (C9-C13) is slightly thinned. The average lateral area per chain in this
      region expands, resulting in a looser packing density. The net effect in the core
      is a 2-3% decrease in density corresponding to a total volume increase of
      approximately 14 cm(3) mol(-1) hexanol partitioned.

PMID- 16887255
TI  - EPR spectroscopy and theoretical study of gamma-irradiated asparagine and
      aspartic acid in solid state.
AB  - Aspartic acid (Asp) and asparagine (Asn) are vulnerable amino acids. One-electron
      addition or withdrawal reactions initiate many deleterious processes involving
      these amino acids. To study these redox processes we have irradiated by gamma
      rays asparagine or aspartic acid in the solid state. The nature of the resulting
      free radicals was determined by electron paramagnetic resonance (EPR) and by
      calculations using DFT methods in various environments. Reactions initiated by
      electron transfer are different for both amino acids: Asn anion loses hydrogen
      atom whereas the cation undergoes decarboxylation. Conversely, Asp cation loses
      hydrogen atom from amine group, which triggers decarboxylation.

PMID- 16887256
TI  - Changes in vibrational modes of water and bioprotectants in solution.
AB  - Inelastic neutron scattering (INS) measurements have been performed on trehalose
      and sucrose/H(2)O mixtures at very low temperature as a function of concentration
      by using the TOSCA spectrometer at the ISIS Facility (DRAL, UK). The aim of this
      work is to investigate by INS the vibrational behaviour of water in presence of
      trehalose and sucrose in order to characterize the changes induced by these
      disaccharides on the H(2)O hydrogen-bonded network. In particular, we obtained
      information about the effects of the two disaccharides in the translational,
      librational and bending spectral regions of ice. The disaccharide bioprotective
      effectiveness can be linked by the high destructuring effect emphasised by the
      analysis of the librational modes region. On the other hand, the analysis of the
      vibrational region corresponding to the ice bending modes show a high
      "crystallinity" degree which can justify the cryptobiotic action of
      disaccharides.

PMID- 16887257
TI  - Sustainable rangeland management using a multi-fuzzy model: how to deal with
      heterogeneous experts' knowledge.
AB  - While fuzzy specialists commonly use homogeneous experts' knowledge to construct
      fuzzy models, it is much more difficult to deal with knowledge elicited from a
      heterogeneous group of experts. This issue is exemplified in the area of
      sustainable rangeland management (SRM). One way to deal with the diversity of
      opinions is to develop a fuzzy system for all experts and to combine all these,
      the so-called primary systems, into one multi-fuzzy model. To derive each of the
      primary fuzzy systems, several semi-structured interviews were held in three
      different areas of the Fars province in Southwest Iran using the knowledge of a
      group of administrative experts. To obtain the final output of the multi-fuzzy
      model, we applied different 'voting' methods. The first method simply uses the
      arithmetic average of the primary outputs as the final output of the multi-fuzzy
      model. This final output represents an estimation of the right rate of stocking
      (RRS). We also propose other (un)supervised voting methods. Most importantly, by
      harmonising the primary outputs such that outliers get less emphasis, we
      introduce an unsupervised voting method for calculating a weighted estimate of
      the RRS. This harmonising method is expected to provide a new useful tool for
      policymakers dealing with heterogenity in experts' opinions: it is especially
      useful where limited field data are available and one is forced to rely on
      experts' knowledge only. By constructing the three fuzzy models based on the
      elicitation of heterogeneous experts' knowledge, our study shows the
      multidimensional vaguenesses that exist in SRM. Finally, by comparing the final
      RRS with its common values, this study strongly points to the existence of
      overgrazing in pastures in the three regions of the Fars province in Southwest
      Iran.

PMID- 16887258
TI  - Analysis of the reasons for exclusion from tPA therapy after early arrival in
      acute stroke patients.
AB  - OBJECTIVE: Only a small percentage of patients with acute stroke receive
      thrombolytic therapy, mainly due to late hospital arrival. Factors excluding
      those who arrive within 3h after stroke onset are less well known. PATIENTS AND
      METHODS: During the first year after implementing a protocol for stroke
      thrombolysis, we prospectively evaluated all patients with stroke admitted to our
      center within 3h from onset. Within-hospital time intervals were calculated and
      the reasons for exclusion from thrombolysis were analyzed. RESULTS: Ninety-six
      patients (representing 16% of all stroke patients admitted) arrived in less than
      3h, and 25 of them (representing 7.5% of all patients with ischemic stroke)
      received thrombolytic therapy, with a door-to-needle interval of 51 min (range,
      33-121). The reasons that accounted for 75% of therapy exclusions were non
      modifiable (a too mild or improving deficit, and intracranial hemorrhage), except
      for a time window exceeded, which would probably require increasing public
      awareness about stroke. CONCLUSIONS: Most reasons for not applying thrombolysis
      to patients who arrive early enough are non-modifiable. Minimizing the door-to
      needle time could compensate for late hospital arrival, which continues to be the
      main reason for not applying this therapy to stroke patients throughout the
      world.

PMID- 16887259
TI  - Magnetoencephalography and diffusion tensor imaging in gelastic seizures
      secondary to a cingulate gyrus lesion.
AB  - Gelastic seizures are relatively uncommon and rarely observed secondary to
      frontal lobe lesions. This report presents magnetoencephalography (MEG) and
      diffusion tensor imaging (DTI) findings in an adolescent with gelastic seizures
      secondary to a left anterior cingulate gyrus lesion. Ictal scalp video EEG showed
      bilateral frontal 4 Hz theta discharges. Interictal EEG showed left fronto
      temporal spikes or sharp waves. Interictal MEG showed spike sources over
      bilateral temporal regions. DTI and tractography delineated slightly shifted
      corpus callosum posterior to the lesion, unaffected uncinate and inferior
      longitudinal fasciculi. The patient became seizure free for 12 months after
      surgical excision of a pleomorphic xanthoastrocytoma in the left anterior
      cingulate region. In our patient, MEG and EEG did not localize the deep-seated
      epileptogenic zone. The combination of DTI and neurophysiologic studies, however,
      possibly disclosed neuronal connections within the epileptic network and
      indicated that epileptic discharges propagated via the uncinate fibers from the
      primary epileptogenic zone in the anterior cingulate region to the mesial
      temporal region in this case with gelastic seizures secondary to a cingulate
      lesion.

PMID- 16887260
TI  - Experimental study of the spill and vaporization of a volatile liquid.
AB  - Pool and vapor cloud characteristics of an acetone spill issuing from the
      downstream wall of a flow obstruction oriented perpendicular to a uniform flow
      were investigated experimentally. Data indicate that the spill event was largely
      governed by the temperature of the surface in relation to the boiling point of
      the spilled liquid. The free stream velocity (ranging from 0.75 to 3.0m/s) also
      impacted the spreading of the spill. Planar laser-induced fluorescence (PLIF) was
      used to measure acetone vapor concentrations during the transient pool spreading
      and vaporization in a window 60cm long by 50cm high and located downstream of the
      16cm high obstruction. The recirculation region induced by the flow obstruction
      caused upstream transport of the acetone vapor along the spill surface, after
      which it was convected vertically along the obstruction wall before being
      entrained into the flow and convected downstream. The recirculating flow caused
      regions of vapor within the flammability limits to be localized near the flow
      obstruction. These regions moved into and out of the measurement plane by large
      three-dimensional flow structures. The flammable region of the evolved vapor
      cloud was observed to grow well past the downstream edge of the measurement
      domain. With decreasing wind speeds, both the mass of acetone vapor within the
      flammability limits and the total spill event time increased significantly. The
      data presented herein provides a basis for validating future spill models of
      hazardous chemical releases, where complex turbulent flow modeling must be
      coupled with spill spreading and vaporization dynamics.

PMID- 16887261
TI  - Risk-based maintenance--techniques and applications.
AB  - Plant and equipment, however well designed, will not remain safe or reliable if
      it is not maintained. The general objective of the maintenance process is to make
      use of the knowledge of failures and accidents to achieve the possible safety
      with the lowest possible cost. The concept of risk-based maintenance was
      developed to inspect the high-risk components usually with greater frequency and
      thoroughness and to maintain in a greater manner, to achieve tolerable risk
      criteria. Risk-based maintenance methodology provides a tool for maintenance
      planning and decision making to reduce the probability of failure of equipment
      and the consequences of failure. In this paper, the risk analysis and risk-based
      maintenance methodologies were identified and classified into suitable classes.
      The factors affecting the quality of risk analysis were identified and analyzed.
      The applications, input data and output data were studied to understand their
      functioning and efficiency. The review showed that there is no unique way to
      perform risk analysis and risk-based maintenance. The use of suitable techniques
      and methodologies, careful investigation during the risk analysis phase, and its
      detailed and structured results are necessary to make proper risk-based
      maintenance decisions.

PMID- 16887262
TI  - Effect of solids concentration on removal of heavy metals from mine tailings via
      bioleaching.
AB  - Mining of mineral ore and disposal of resulting waste tailings pose a significant
      risk to the surrounding environment. The objective of this work is to demonstrate
      the feasibility to remove heavy metals from mine tailings with the use of
      bioleaching and meanwhile to investigate the effect of solids concentration on
      removal of heavy metals from mine tailings by indigenous sulfur-oxidizing
      bacteria and the transformation of heavy metal forms after the bioleaching
      process. This work showed the laboratory results of bioleaching experiments on Pb
      Zn-Cu mine tailings. The results showed that 98.08% Zn, 96.44% Cu, and 43.52% Pb
      could be removed from mine tailings by the bioleaching experiment after 13 days
      at 1% (w/v) solids concentration and the rates of pH reduction, ORP rise and
      sulfate production were reduced with the increase of solids concentration, due to
      the buffering capacity of mine tailing solids. The results also indicated that
      solid concentration 1% was found to be best to bacterial activity and metal
      solubilization of the five solids concentration tested (1%, 2%, 5%, 8% and 10%)
      under the chosen experimental conditions. In addition, the bioleaching had a
      significant impact on changes in partitioning of heavy metals.

PMID- 16887263
TI  - Adsorption of direct dye on palm ash: kinetic and equilibrium modeling.
AB  - Palm ash, an agriculture waste residue from palm-oil industry in Malaysia, was
      investigated as a replacement for the current expensive methods of removing
      direct blue 71 dye from an aqueous solution. The experimental data were analyzed
      by the Langmuir and Freundlich models of adsorption. Equilibrium data fitted well
      with Freundlich model in the range of 50-600mg/L. The equilibrium adsorption
      capacity of the palm ash was determined with the Langmuir equation and found to
      be 400.01mg dye per gram adsorbent at 30 degrees C. The rates of adsorption were
      found to conform to the pseudo-second-order kinetics with good correlation. The
      results indicate that the palm ash could be employed as a low-cost alternative to
      commercial activated carbon.

PMID- 16887264
TI  - Thermal characteristics of lysine tri-isocyanate and its mixture with water.
AB  - The thermal reactivity of lysine tri-isocyanate (LTI, 2-isocyanatoethyl-2,6
      diisocyanato caproylate) and its mixture with 1% water was investigated after the
      occurrence of a runaway reaction at a plant. By using a sensitive thermal
      calorimeter, C80, and an adiabatic calorimeter, ARC, an onset reaction of LTI was
      observed at 70-100 degrees C and it became vigorous at 175-200 degrees C. The
      reaction is considered as co-polymerization at this stage, which causes a second
      decomposition reaction at 200 degrees C if the heat generation is accumulated in
      the vessel. On the other hand, the presence of water can catalyze LTI at much
      lower onset temperature and lead to a moderate reaction at 50 degrees C since
      carbamine is produced and in turn it induces decarbonization of the LTI molecule
      with significant release of CO2 gas which was detected by a gas chromatography
      and an FT-IR gas analyzer.

PMID- 16887265
TI  - Melamine-formaldehyde-NTA chelating gel resin: Synthesis, characterization and
      application for copper(II) ion removal from synthetic wastewater.
AB  - A new chelating resin was synthesised by anchoring nitrilotriacetic acid (NTA) to
      melamine during the melamine-formaldehyde gelling reaction in the presence of
      water, using acetone and guaiacol as a porogen mixture. This technique gives a
      porous chelating gel resin capable of removing heavy metals from wastewater. FT
      IR, XRD, elemental analysis, surface area and water regain measurements were
      conducted for characterization of the new chelating gel resin. A comprehensive
      adsorption study (kinetics isotherm, and thermodynamics) of Cu(II) removal from
      synthetic acidic aqueous solutions by adsorption on this resin was conducted
      regarding the effects of time, temperature, initial pH and copper(II) initial
      concentration.

PMID- 16887266
TI  - The operation characteristics and electrochemical reactions of a specific
      circulation-enhanced electrokinetics.
AB  - For electrokinetics remediation, the acid produced at the anode due to the water
      electrolysis will cause the soil acidification and destroy the soil constituents.
      Especially, the contaminated soils in Taiwan are usually agricultural lands; it
      is necessary to improve the performance of EK system to maintain the soils nature
      after remediation. In this study, a circulation-enhanced EK system (CEEK) was
      designed to neutralize the pH of the working solution and soils. Experiments were
      conducted by the control of different electrolyte species (sodium and potassium
      salts) and concentrations (10(-3) to 5x10(-2)M), respectively. Experimental
      results show the operational characteristics include: the CEEK system can
      effectively stabilize the pH of processing solution at neutral range and the
      current can be maintained at stable status with carbonate salts; the pH buffering
      range of working solution in the CEEK system depends on the electrolyte species
      and their concentration significantly; the water content remains roughly as their
      original nature in the CEEK system. For consideration of electrochemical
      reactions, the water electrolysis is the predominating electrochemical reaction
      in the CEEK system, which not only influences the pH but also the conductivity of
      the working solution. In the application of practical engineering, there exist
      linear relationships between the pH, conductivity, current and the electrolyte
      concentration, respectively, which can serve as a means to assist engineers to
      select operational parameters of CEEK.

PMID- 16887267
TI  - Keys to effective third-party process safety audits.
AB  - The Occupational Safety and Health Administration's (OSHA's) Process Safety
      Management (PSM) regulation was promulgated in 1992. The U.S. Environmental
      Protection Agency's (EPA's) corresponding Risk Management Program (RMP) rule
      followed in 1996. Both programs include requirements for triennial compliance
      audits. Effective compliance audits are critical in identifying program
      weaknesses and ensuring the safety of facility personnel and the surrounding
      public. Large companies with corporate and facility health, safety, and
      environmental groups typically have the resources and experience to conduct
      audits internally, either through a corporate audit team or the sharing of
      personnel between multiple facilities. Small to medium sized businesses
      frequently do not have the expertise or the resources to perform compliance
      audits, and rely on third-party consultants to provide these services. This paper
      will discuss the observations of the authors in performing audits and working
      with PSM/RMP programs across a number of market sectors (e.g. chemical,
      petrochemical, pharmaceutical, food and beverage, water treatment), including
      effective practices, hurdles to successful implementation and execution of
      programs, and typical program shortcomings. The paper will also discuss steps to
      improve the audit process and increase effectiveness whether performed by a third
      party or internally.

PMID- 16887268
TI  - Equilibrium and kinetic studies for the sorption of 3-methoxybenzaldehyde on
      activated kaolinites.
AB  - The sorption of 3-methoxybenzaldehyde on activated kaolinites has been
      investigated at different temperatures. Two types of activation tests were
      performed. The sorption equilibrium was studied by sorption isotherms in the
      temperature range 303-333K for natural (untreated), thermally and acid activated
      kaolinites. It was shown that the isotherm shapes were not affected by
      temperature and activation types of kaolinite. The absorbance data at 312nm were
      fitted reasonably well with the Langmuir and Freundlich isotherm models and the
      model parameters were determined for different temperatures. Thermodynamic
      quantities such as Gibbs free energy (DeltaG), the enthalpy (DeltaH) and the
      entropy change of sorption (DeltaS) were determined for natural, thermally and
      acid activated kaolinites. It was shown that the sorption processes were an
      endothermic reactions, controlled by physical mechanisms and spontaneously.
      Adsorption capacity of acid activated kaolinite for 3-methoxybenzaldehyde was
      higher compared to that of natural and thermally activated kaolinites at various
      temperatures. The adsorption and desorption rate constants (k(a) and k(d)) were
      obtained separately by applying a geometric approach to the first order Langmuir
      model. This method provided good conformity between the K from Langmuir
      parameters and K(geo) (k(a)/k(d)) from geometric approach.

PMID- 16887270
TI  - Prevalence and incidence of bovine trypanosomosis on the Adamaoua plateau in
      Cameroon 10 years after the tsetse eradication campaign.
AB  - Between March 2004 and February 2005, the monthly incidence of trypanosome
      infections was measured in cattle from nine sentinel herds in the Adamaoua
      province of Cameroon. Three herds of 20 cattle each were kept on the plateau
      which has been cleared from tsetse flies about 10 years ago, three other herds
      were grazing in the tsetse infested valley whereas the last three were herded in
      the buffer zone. The cross-sectional study showed that the initial trypanosomosis
      prevalence was 1.8, 5.2 and 2.0% on the plateau, in the buffer zone and the
      valley, respectively. During the longitudinal study, the trypanosomosis incidence
      was high in the valley (3.7-20%) and the buffer zone (1.8-13.4%), whereas it was
      significantly lower (0-2.1%) on the plateau. Tsetse flies, mainly Glossina
      morsitans submorsitans and a few G. tachinoides, were caught in the valley and
      the buffer zone, but none on the plateau. The data indicate a low trypanosomosis
      risk on the plateau. Further entomological studies, however, are required to
      clarify the origin of the trypanosome infections on the plateau.

PMID- 16887269
TI  - The effect of mixed or sequential grazing of cattle and sheep on the faecal egg
      counts and growth rates of weaned lambs when treated with anthelmintics.
AB  - An experiment was conducted over two successive years (2002 and 2003) to
      investigate the effects of grazing improved permanent pasture (mainly perennial
      ryegrass/white clover) by cattle or sheep, either sequentially or mixed, on the
      faecal egg counts and growth rates of weaned lambs when treated with
      anthelmintics. The grazing season was divided into two parts, May-July then July
      October, relating to the pre- and post-weaning of the lambs. Four grazing
      regimes, replicated three times, were compared: (1) sheep only from May to
      October (SS); (2) cattle May to July followed by lambs until October (C/S); (3)
      cattle and sheep May to July followed by lambs until October (C+S/S); and (4)
      cattle and sheep May to July followed by cattle and lambs until October
      (C+S/C+S). Sward height was maintained at 6 cm using a "put and take" stocking
      system. At weaning, lambs were weighed and treated with an anthelmintic (0.08%
      ivermectin drench, Oramec) before being allocated to plots. They were then
      weighed and drenched every 28 days until the end of the experiment (Day 84).
      Faecal egg counts (FEC) were measured in all lambs immediately prior to each
      anthelmintic treatment. In 2002 and 2003, there were differences between the
      groups in FEC, with the SS lambs having the highest values and C/S lambs the
      lowest (P<0.01). There were also differences in the rate of liveweight gain of
      the lambs in each of the study years: for this parameter SS lambs had the lowest
      growth rate but the fastest growth was in C+S/C+S lambs not C/S lambs (P<0.01),
      indicating that these differences were due to factors other than parasite
      infection. Overall, sequential grazing of pastures with cattle then sheep reduced
      the faecal egg counts in lambs regularly treated with anthelmintics when compared
      with lambs grazing in mixed systems with cattle and sheep or with sheep only
      systems, however, the highest growth rates were observed in lambs in the mixed
      cattle/sheep grazing system throughout.

PMID- 16887271
TI  - Human pancreatic lipase-related protein 2: tissular localization along the
      digestive tract and quantification in pancreatic juice using a specific ELISA.
AB  - Human pancreatic lipase-related protein 2 (HPLRP2) was previously found to be
      secreted by the exocrine pancreas. HPLRP2 shows a high level of activity on
      galactolipids, and might be involved in the digestion of these common vegetable
      lipids. Specific antibodies were raised in rabbits using a synthetic HPLRP2
      peptide selected for its weak amino acid homology with the corresponding peptides
      of classical human pancreatic lipase (HPL) and human pancreatic lipase-related
      protein 1 (HPLRP1). ELISA and Western blotting data showed that these antibodies
      did not react with HPL or HPLRP1. Various tissues from the digestive tract were
      subjected to Western blotting analysis with the specific anti-peptide HPLRP2
      antibody and the expression of HPLRP2 was detected in the pancreas and colon. An
      ELISA was developed for specifically measuring the HPLRP2 levels in pure
      pancreatic juice. This procedure was performed using the anti-peptide HPLRP2
      antibody as the captor antibody and a biotinylated anti-HPLRP2 polyclonal
      antibody as the detector antibody. The lowest HPLRP2 quantification limit was
      found to be 50 microg/L and the reference range for the present assay was 50
      microg-500 microg/L. HPL and HPLRP2 levels were measured using specific ELISAs in
      pancreatic juice from patients with and without pancreatic disorders. Patients
      with chronic calcifying pancreatitis (CCP) had significantly lower levels of both
      HPL and HPLRP2 than the controls subjects. The mean HPLRP2 to HPL ratio was
      estimated to be 28.30% (w/w) and 23.96% (w/w) in controls subjects and CCP
      patients, respectively, and the difference was not significant. The levels of HPL
      and HPLRP2 are therefore similarly reduced in both healthy patients and CCP
      patients.

PMID- 16887272
TI  - Radiotherapy-induced taste impairment.
AB  - Changes in taste perception occur in a significant proportion of cancer patients.
      Among cancer patients treated with radiotherapy (RT) in head and neck area, the
      vast majority reports an altered taste sense during and after treatments. Taste
      impairment starts a few weeks after the beginning of irradiation, and almost all
      such patients experienced loss of taste acuity at a dose of 60 Gy. Some studies
      investigated the four basic taste intensities (sweet, salty, sour and bitter) and
      the umami taste, and several of these reports identified diminished threshold
      sensitivity for at least one taste quality. Six months to one year after RT,
      taste acuity recovers to its previous level in many patients, but some patients
      show incomplete or no recovery even several years later. Taste impairment has
      profound effects on patients' quality of life because is associated with weight
      loss through reduced appetite and altered patterns of food intake. Damage to the
      major salivary glands during head and neck RT leads to disturbance in taste
      acuity. With the implementation of new radiation techniques, such as conformal
      and intensity-modulated RT in head and neck irradiation, the late-radiation
      effects can probably be reduced, but the remaining sequelae are still bothersome
      to the patients.

PMID- 16887274
TI  - Differential gene expression in the rat cochlea after exposure to impulse noise.
AB  - Understanding the molecular biology of noise trauma is vital to developing
      effective and timely interventions. In a model of explosion-mediated impulse
      noise injury, differential gene expression was studied in whole rat cochlea
      preparations at 3 and 24 h following the exposure. We developed a technique using
      mRNA from a single cochlea on each oligonucleotide microarray to avoid pooling of
      mRNA samples. Application of a conservative statistical analysis approach
      resulted in the identification of 61 differentially expressed genes. Within 3 h
      after the exposure, there was an up-regulation of immediate early genes, mainly
      transcription factors and genes involved in the tissue's response to oxidative
      stress. No genes were found to be significantly down-regulated. At 24 h following
      the exposure, up-regulated genes included members of inflammatory and antioxidant
      pathways and one gene involved in glutathione metabolism was down-regulated. A
      subset of genes was confirmed by real-time reverse transcriptase-polymerase chain
      reaction (RT-PCR). The present study demonstrates the power of the microarray
      technique in providing a global view of the gene regulation following noise
      exposure, and in identifying genes that may be mechanistically important in
      hearing loss, and thereby serve as a basis for the development of therapeutic
      interventions.

PMID- 16887273
TI  - Regulation of synaptic input to hypothalamic presympathetic neurons by GABA(B)
      receptors.
AB  - The hypothalamic paraventricular (PVN) neurons projecting to the spinal cord and
      brainstem play an important role in the control of homeostasis and the
      sympathetic nervous system. Although GABA(B) receptors are present in the PVN,
      their function in the control of synaptic inputs to PVN presympathetic neurons is
      not clear. Using retrograde tracing and whole-cell patch-clamp recordings in rat
      brain slices, we determined the role of presynaptic GABA(B) receptors in
      regulation of glutamatergic and GABAergic inputs to spinally projecting PVN
      neurons. The GABA(B) receptor agonist baclofen (1-50 microM) dose-dependently
      decreased the frequency but not the amplitude of spontaneous excitatory
      postsynaptic currents (sEPSCs) and inhibitory postsynaptic currents (sIPSCs). The
      effect of baclofen on sEPSCs and sIPSCs was completely blocked by 10 microM
      CGP52432, a selective GABA(B) receptor antagonist. Baclofen also significantly
      reduced the frequency of both miniature excitatory and miniature inhibitory
      postsynaptic currents (mEPSCs and mIPSCs). Furthermore, uncoupling pertussis
      toxin-sensitive G(i/o) proteins with N-ethylmaleimide abolished baclofen-induced
      inhibition of mEPSCs and mIPSCs. However, the inhibitory effect of baclofen on
      the frequency of mIPSCs and mEPSCs persisted in the presence of either Cd2+, a
      voltage-gated Ca2+ channel blocker, or 4-aminopyridine, a blocker of voltage
      gated K+ channels. Our results suggest that activation of presynaptic GABA(B)
      receptors inhibits synaptic GABA and glutamate release to PVN presympathetic
      neurons. This presynaptic action of GABA(B) receptors is mediated by the N
      ethylmaleimide-sensitive G(i/o) proteins, but independent of voltage-gated Ca2+
      and K+ channels.

PMID- 16887275
TI  - Olfactory bulb networks revealed by lateral olfactory tract stimulation in the in
      vitro isolated guinea-pig brain.
AB  - Olfactory information processing is mediated by synaptic connections between the
      olfactory bulbs (OBs) and piriform-limbic cortices. Limited accessibility using
      common in vivo and in vitro preparations has hindered previous attempts to define
      these synaptic interactions. We utilized the isolated guinea-pig brain
      preparation to overcome these experimental limitations. Previous studies
      demonstrated extensive functional preservation in this preparation maintained in
      vitro by arterial perfusion. Field potential laminar profiles were performed with
      multi-channel probes in the OB following stimulation of both the lateral
      olfactory tract (LOT) and the anterior piriform cortex (APC). Current-source
      density analysis was carried out on laminar profiles to reconstruct current
      sinks/sources associated with intrinsic synaptic activities. LOT stimulation
      induced sequentially i) an antidromic population spike (at 2.66+/-0.39 ms)
      located in the mitral cell layer that was resistant to 100 Hz high-frequency
      stimulation (HFS) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) (10 microM),
      ii) a component located in the external plexiform layer at 3.85+/-0.63 ms that
      was unaffected by HFS, iii) a large amplitude potential (peak amplitude at 5.84+/
      0.58 ms) generated in the external plexiform layer, abolished by HFS and CNQX,
      but not by bicuculline (50 microM), iv) a late response (onset at 20.00+/-2.94
      ms) abolished by CNQX and enhanced by bicuculline. Stimulation of the APC also
      induced a late potential abolished by HFS and CNQX. Both APC-evoked and late LOT
      evoked responses were abolished by a transverse cut to separate OB from APC.
      These results demonstrate in an isolated mammalian brain preparation the presence
      of reciprocal synaptic interactions between the OB and piriform cortical
      structures.

PMID- 16887277
TI  - Interactions among the medial prefrontal cortex, hippocampus and midline thalamus
      in emotional and cognitive processing in the rat.
AB  - The medial prefrontal cortex (mPFC) participates in several higher order
      functions including selective attention, visceromotor control, decision making
      and goal-directed behaviors. We discuss the role of the infralimbic cortex (IL)
      in visceromotor control and the prelimbic cortex (PL) in cognition and their
      interactions in goal-directed behaviors in the rat. The PL strongly interconnects
      with a relatively small group of structures that, like PL, subserve cognition,
      and together have been designated the 'PL circuit.' These structures primarily
      include the hippocampus, insular cortex, nucleus accumbens, basolateral nucleus
      of the amygdala, the mediodorsal and reuniens nuclei of the thalamus and the
      ventral tegmental area of the midbrain. Lesions of each of these structures, like
      those of PL, produce deficits in delayed response tasks and memory. The PL (and
      ventral anterior cingulate cortex) (AC) of rats is ideally positioned to
      integrate current and past information, including its affective qualities, and
      act on it through its projections to the ventral striatum/ventral pallidum. We
      further discuss the role of nucleus reuniens of thalamus as a major interface
      between the mPFC and the hippocampus, and as a prominent source of afferent
      limbic information to the mPFC and hippocampus. We suggest that the IL of rats is
      functionally homologous to the orbitomedial cortex of primates and the prelimbic
      (and ventral AC) cortex to the lateral/dorsolateral cortex of primates, and that
      the IL/PL complex of rats exerts significant control over emotional and cognitive
      aspects of goal-directed behavior.

PMID- 16887278
TI  - Increased apoptosis in rat brain after rapid eye movement sleep loss.
AB  - Rapid eye movement (REM) sleep loss impairs several physiological, behavioral and
      cellular processes; however, the mechanism of action was unknown. To understand
      the effects of REM sleep deprivation on neuronal damage and apoptosis, studies
      were conducted using multiple apoptosis markers in control and experimental rat
      brain neurons located in areas either related to or unrelated to REM sleep
      regulation. Furthermore, the effects of REM sleep deprivation were also studied
      on neuronal cytoskeletal proteins, actin and tubulin. It was observed that after
      REM sleep deprivation a significantly increased number of neurons in the rat
      brain were positive to apoptotic markers, which however, tended to recover after
      the rats were allowed to undergo REM sleep; the control rats were not affected.
      Further, it was also observed that REM sleep deprivation decreased amounts of
      actin and tubulin in neurons confirming our previous reports of changes in
      neuronal size and shape after such deprivation. These findings suggest that one
      of the possible functions of REM sleep is to protect neurons from damage and
      apoptosis.

PMID- 16887276
TI  - Robust increase of cutaneous sensitivity, cytokine production and sympathetic
      sprouting in rats with localized inflammatory irritation of the spinal ganglia.
AB  - We investigated the role and mechanisms of inflammatory responses within the
      dorsal root ganglion (DRG) in the development of chemogenic pathological pain.
      DRG inflammation was induced by a single deposit of the immune activator zymosan
      in incomplete Freund's adjuvant in the epidural space near the L5 DRG via a small
      hole drilled through the transverse process. After a single zymosan injection,
      rats developed bilateral mechanical hyperalgesia and allodynia which began by day
      1 after surgery, peaked at days 3-7, and lasted up to 28 days. The number of
      macrophages in ipsilateral and contralateral DRGs increased significantly,
      lasting over 14 days. Robust glial activation was observed in inflamed ganglia.
      Cytokine profile analysis using a multiplexing protein array system showed that,
      in normal DRG, all but interleukin (IL)-5, IL-10 and granulocyte-macrophage
      colony stimulating factor (GM-CSF) were detectable with concentrations of up to
      180 pg/mg protein. Local inflammatory irritation selectively increased IL-1beta,
      IL-6, IL-18, monocyte chemoattractant protein-1 (MCP-1), and growth-related
      oncogene (GRO/KC) up to 17-fold, and decreased IL-2 and IL-12 (p70) up to
      threefold. Inflaming the DRG also remarkably increased the incidence of
      spontaneous activity of A- and C-fibers recorded in the dorsal root. Many of the
      spontaneously active A-fibers exhibited a short-bursting discharge pattern.
      Changes in cytokines and spontaneous activity correlated with the time course of
      pain behaviors, especially light stroke-evoked tactile allodynia. Finally, local
      inflammation induced extensive sprouting of sympathetic fibers, extending from
      vascular processes within the inflamed DRG. These results demonstrate the
      feasibility of inducing chronic localized inflammatory responses in the DRG in
      the absence of traumatic nerve damage, and highlight the possible contribution of
      several inflammatory cytokines/chemokines to the generation of spontaneous
      activity and development and persistence of chemogenic pathologic pain.

PMID- 16887279
TI  - Beta-endorphin involvement in the regulatory response to body sodium overload.
AB  - The present study was performed to examine the role of the endogenous beta
      endorphinergic system on blood pressure regulation, sympathetic and brain
      activity during body sodium overload. Beta-endorphin knockout (beta end-/-),
      heterozygous (beta end+/-) and wild-type (beta end+/+) mice were submitted for
      two weeks to either a normal- or a high-sodium diet (NSD and HSD, respectively),
      and systolic blood pressure (SBP), urinary catecholamines (as an index of
      sympathetic nervous system activity), and the brain pattern of Fos-like
      immunoreactivity (as a marker of neuronal activation) were evaluated in each
      group. HSD caused a significant increase in SBP in beta end-/- mutant mice
      compared with beta end+/+ mice kept in the same experimental conditions (P <
      0.01), but no statistical differences were observed between beta end+/- and beta
      end+/+ on a HSD. Moreover, when animals from the three genetic lines were fed
      with a NSD no changes in SBP were evidenced. With regard to brain activity, beta
      end-/- mice maintained on a HSD showed a significant increase in Fos-like
      immunoreactive neurons in the median preoptic nucleus (P < 0.01) compared with
      beta end+/- and beta end+/+ animals. Additionally, beta end-/- mice had higher
      levels of urinary epinephrine excretion (P < 0.05) on a HSD in comparison to beta
      end+/+ and beta end+/- animals in the same experimental conditions. No
      differences, however, were registered in norepinephrine and dopamine urinary
      excretion in animals from the three genetic lines after two weeks on either a HSD
      or a NSD. In summary, our results indicate that the beta-endorphinergic system
      may play a part in the compensatory response to sodium overload, since the
      absence of beta-endorphin causes an increase in systolic blood pressure, and
      increases median preoptic nucleus neural activity and urinary epinephrine
      excretion.

PMID- 16887280
TI  - Mu opioid receptor-effector coupling and trafficking in dorsal root ganglia
      neurons.
AB  - Morphine induces profound analgesic tolerance in vivo despite inducing little
      internalization of the mu opioid receptor (muOR). Previously proposed
      explanations suggest that this lack of internalization could either lead to
      prolonged signaling and associated compensatory changes in downstream signaling
      systems, or that the receptor is unable to recycle and resensitize and so loses
      efficacy, either mechanism resulting in tolerance. We therefore examined, in
      cultured neurons, the relationship between muOR internalization and
      desensitization in response to two agonists, D-Ala2, N-MePhe4, Gly5-ol-enkephalin
      (DAMGO) and morphine. In addition, we studied the chimeric mu/delta opioid
      receptor (mu/ partial differentialOR) which could affect internalization and
      desensitization in neurons. Dorsal root ganglia neurons from muOR knockout mice
      were transduced with an adenovirus expressing either receptor and their
      respective internalization, desensitization and trafficking profiles determined.
      Both receptors desensitized equally, measured by Ca2+ current inhibition, during
      the first 5 min of agonist exposure to DAMGO or morphine treatment, although the
      mu/partial differentialOR desensitized more extensively. Such rapid
      desensitization was unrelated to internalization as DAMGO, but not morphine,
      internalized both receptors after 20 min. In response to DAMGO the mu/partial
      differentialOR internalized more rapidly than the muOR and was trafficked through
      Rab4-positive endosomes and lysosomal-associated membrane protein-1-labeled
      lysosomes whereas the muOR was trafficked through Rab4 and Rab11-positive
      endosomes. Chronic desensitization of the Ca2+ current response, after 24 h of
      morphine or DAMGO incubation, was seen in the DAMGO, but not morphine-treated,
      muOR-expressing cells. Such persistence of signaling after chronic morphine
      treatment suggests that compensation of downstream signaling systems, rather than
      loss of efficacy due to poor receptor recycling, is a more likely mechanism of
      morphine tolerance in vivo. In contrast to the muOR, the mu/partial
      differentialOR showed equivalent desensitization whether morphine or DAMGO
      treated, but internalized further with DAMGO than morphine. Such ligand
      independent desensitization could be a result of the observed higher rate of
      synthesis and degradation of this chimeric receptor.

PMID- 16887281
TI  - Nonreporting of cannabis use: Predictors and relationship to treatment outcome in
      methadone maintained patients.
AB  - Underreporting of drug use is common and influenced by multiple factors. Cannabis
      (THC) use nonreporting and its relationship to heroin and cocaine use were
      investigated in 690 patients enrolled in 25- to 29-week clinical trials of
      contingency management plus methadone maintenance. Urine specimens and self
      reports of drug use were collected 3 times/week. Potential predictors of THC use
      nonreporting were analyzed by multiple logistic regression; relationships between
      THC use nonreporting and % cocaine- and opiate-positive urines were analyzed by
      multiple regression. Compared to non-THC users (n=317), patients with THC
      positive urines (n=373) were more likely to be male and have more years of THC
      use, but were not different on other characteristics. Nonreporting to user ratios
      were: THC 191/373 (51.2%); opiates 17/686 (2.5%); cocaine 21/681 (3.1%).
      Predictors of THC use nonreporting were low rate of THC-positive urines during
      treatment, fewer days of THC use in the last 30 before treatment, African
      American race, and absence of antisocial personality disorder. Nonreporting of
      THC use was associated with significantly greater opiate and cocaine use.
      Contingency management decreased cocaine use in THC nonreporters to the level of
      reporters. Nonreporting of THC use is a significant predictor of greater cocaine
      and heroin use. This association can be eliminated with contingency management
      therapy.

PMID- 16887282
TI  - Targeting cerebral Bcl-2 expression as a potential therapeutic target in autism:
      potential usefulness of human recombinant nerve growth factor.

PMID- 16887283
TI  - Mustard lung secrets: long term clinicopathological study following mustard gas
      exposure.
AB  - Considering the undefinite nature of lung pathology in patients exposed to sulfur
      mustard (SM) many years after exposure, we conducted this study to document and
      quantify lung disease in this setting. In a cross sectional study, we selected 23
      patients exposed to SM gas approximately 14 years ago during the Iran-Iraq war
      (1980-1988). We studied their clinical history, physical examination, pulmonary
      function test (PFT), high-resolution computed tomography scan (HRCT) of the
      chest, bronchoscopy, and bronchoalveolar lavage (BAL) sampling, and
      transbronchial lung biopsies. Other potential causes of lung disease, including
      smoking of cigarettes, were excluded. All 23 patients were symptomatic with
      cough, dyspnea, and/or felt tight in the chest. All of them had significant air
      trapping in HRCT and a marked increase of residual volume in PFT. The most common
      inflammatory cell in BAL fluid was neutrophil (88%). Of the 23 cases, there was
      sufficient tissue for detailed evaluation in 22. Histologically, 11 cases showed
      airway epithelial injury, and nine of the 14 lung biopsies with alveoli had
      histopathological changes diagnosable as organizing pneumonia (OP) or
      bronchiolitis obliterans OP (BOOP). Two out of 14 cases showed changes suggestive
      of OP. Inhalation of SM can lead to persistant and clinically significant lung
      disease, including bronchial mucosal injury and OP, many years after exposure.

PMID- 16887284
TI  - Corpuscular thymoma: entity or variant of organotypical thymomas WHO B2/B3?
AB  - Hassall's corpuscles are regular structures in the medulla of the normal thymus
      and in non-neoplastic thymic conditions, e.g. in multilocular thymic cysts. In
      thymomas, however, they are inconsistently found, and are believed to indicate
      medullary differentiation of WHO type B1-3 thymomas. We present five
      organotypical thymomas resembling WHO type B2 and B3 thymomas, but with an
      abundance of Hassall's corpuscles. We wonder whether this exceedingly rare
      observation might herald a distinct entity. Four tumors were asymptomatic,
      incidental findings and of low Masaoka stage (I or II) [20] . One patient
      suffered from myasthenia gravis which disappeared upon surgical removal of the
      thymus, while all other patients had no concomitant autoimmune disease. Two
      patients had a relapse-free follow-up of 12 and 2 years, respectively, upon
      curative surgery, and another tumor was an autopsy finding; follow-up data of two
      more recent cases was not yet available. The neoplastic epithelium other than
      Hassall's corpuscles was arranged either in a cortical type B2 pattern or in type
      B3 solid cords. In all examples, there was cyst formation, inflammatory reaction
      and repair, indicative of a long-standing condition. Immature T cells were
      present in all instances. "Corpuscular thymomas" morphologically resemble WHO
      type B2 and B3 thymomas, but appear biologically indolent and are rarely
      associated with myasthenia gravis. Whether they qualify for a separate entity has
      to be proven by larger series, including genetic studies.

PMID- 16887285
TI  - Phase II Radiation Therapy Oncology Group trial of conventional radiation therapy
      followed by treatment with recombinant interferon-beta for supratentorial
      glioblastoma: results of RTOG 9710.
AB  - PURPOSE: The aim of this study was to determine whether recombinant human
      interferon beta-1a (rhIFN-beta), when given after radiation therapy, improves
      survival in glioblastoma. METHODS AND MATERIALS: After surgery, 109 patients with
      newly diagnosed supratentorial glioblastoma were enrolled and treated with
      radiation therapy (60 Gy). A total of 55 patients remained stable after radiation
      and were treated with rhIFN-beta (6 MU/day i.m., 3 times/week). Outcomes were
      compared with the Radiation Therapy Oncology Group glioma historical database.
      RESULTS: RhIFN-beta was well tolerated, with 1 Grade 4 toxicity and 8 other
      patients experiencing Grade 3 toxicity. Median survival time (MST) of the 55
      rhIFN-beta-treated patients was 13.4 months. MST for the 34 rhIFN-beta-treated in
      RPA Classes III and IV was 16.9 vs. 12.4 months for historical controls (hazard
      ratio [HR] = 1.27, 95% confidence interval [CI] = 0.89-1.81). There was also a
      trend toward improved survival across all RPA Classes comparing the 55 rhIFN-beta
      treated patients and 1,658 historical controls (HR = 1.24, 95% CI = 0.94-1.63).
      The high rate of early failures (54/109) after radiation and before initiation of
      rhIFN-beta was likely caused by stricter interpretation of early radiographic
      changes in the current study. Matched-pair and intent-to-treat analyses performed
      to try to address this bias showed no difference in survival between study
      patients and controls. CONCLUSION: RhIFN-beta given after conventional radiation
      therapy was well tolerated, with a trend toward survival benefit in patients who
      remained stable after radiation therapy. These data suggest that rhIFN-beta
      warrants further evaluation in additional studies, possibly in combination with
      current temozolomide-based regimens.

PMID- 16887286
TI  - Comparison of risk of local-regional recurrence after mastectomy or breast
      conservation therapy for patients treated with neoadjuvant chemotherapy and
      radiation stratified according to a prognostic index score.
AB  - PURPOSE: We previously developed a prognostic index that stratified patients
      treated with breast conservation therapy (BCT) after neoadjuvant chemotherapy
      into groups with different risks for local-regional recurrence (LRR). The purpose
      of this study was to compare the rates of LRR as a function of prognostic index
      score for patients treated with BCT or mastectomy plus radiation after
      neoadjuvant chemotherapy. METHODS: We retrospectively analyzed 815 patients
      treated with neoadjuvant chemotherapy, surgery, and radiation. Patients were
      assigned an index score from 0 to 4 and given 1 point for the presence of each
      factor: clinical N2 to N3 disease, lymphovascular invasion, pathologic size>2 cm,
      and multifocal residual disease. RESULTS: The 10-year LRR rates were very low and
      similar between the mastectomy and BCT groups for patients with an index score of
      0 or 1. For patients with a score of 2, LRR trended lower for those treated with
      mastectomy vs. BCT (12% vs. 28%, p=0.28). For patients with a score of 3 to 4,
      LRR was significantly lower for those treated with mastectomy vs. BCT (19% vs.
      61%, p=0.009). CONCLUSIONS: This analysis suggests that BCT can provide excellent
      local-regional treatment for the vast majority of patients after neoadjuvant
      chemotherapy. For the few patients with a score of 3 to 4, LRR was >60% after BCT
      and was <20% with mastectomy. If these findings are confirmed in larger
      randomized studies, the prognostic index may be useful in helping to select the
      type of surgical treatment for patients treated with neoadjuvant chemotherapy,
      surgery, and radiation.

PMID- 16887287
TI  - Proton or photon irradiation for hemangiomas of the choroid? A retrospective
      comparison.
AB  - PURPOSE: The aim of this study was to compare, on a retrospective basis, the
      results of therapy in patients with uveal hemangioma treated with photon or
      proton irradiation at a single center. METHODS: From 1993 to 2002 a total of 44
      patients were treated. Until 1998 radiotherapy was given with 6 MV photons in
      standard fractionation of 2.0 Gy 5 times per week. In 1998 proton therapy became
      available and was used since then. A dose of 20 to 22.5 Cobalt Gray Equivalent
      (CGE) 68 MeV protons was given on 4 consecutive days. Progressive symptoms or
      deterioration of vision were the indications for therapy. RESULTS: Of the 44
      patients treated, 36 had circumscribed choroidal hemangiomas and 8 had diffuse
      choroidal hemangiomas (DCH) and Sturge-Weber syndrome. Of the patients, 19 were
      treated with photons with a total dose in the range of 16 to 30 Gy. A total of 25
      patients were irradiated with protons. All patients with DCH but 1 were treated
      with photons. Stabilization of visual acuity was achieved in 93.2% of all
      patients. Tumor thickness decreased in 95.4% and retinal detachment resolved in
      92.9%. Late effects, although generally mild or moderate, were frequently
      detected. In all, 40.9% showed radiation-induced optic neuropathy, maximum Grade
      I. Retinopathy was found in 29.5% of cases, but only 1 patient experienced more
      than Grade II severity. Retinopathy and radiation-induced optic neuropathy were
      reversible in some of the patients and in some resolved completely. No
      differences could be detected between patients with circumscribed choroidal
      hemangiomas treated with protons and photons. Treatment was less effective in DCH
      patients (75%). CONCLUSIONS: Radiotherapy is effective in treating choroidal
      hemangiomas with respect to visual acuity and tumor thickness but a benefit of
      proton therapy could not be detected. Side effects are moderate but careful
      monitoring for side effects should be part of the follow-up procedures.

PMID- 16887288
TI  - Low local recurrence rate without postmastectomy radiation in node-negative
      breast cancer patients with tumors 5 cm and larger.
AB  - PURPOSE: To assess the need for adjuvant radiotherapy following mastectomy for
      patients with node-negative breast tumors 5 cm or larger. METHODS AND MATERIALS:
      Between 1981 and 2002, a total of 70 patients with node-negative breast cancer
      and tumors 5 cm or larger were treated with mastectomy and adjuvant systemic
      therapies but without radiotherapy at three institutions. We retrospectively
      assessed rates and risk factors for locoregional failure (LRF), overall survival
      (OS), and disease-free survival (DFS) in these patients. RESULTS: With a median
      follow-up of 85 months, the 5-year actuarial LRF rate was 7.6% (95% confidence
      interval, 3%-16%). LRF was primarily in the chest wall (4/5 local failures), and
      lymphatic-vascular invasion (LVI) was statistically significantly associated with
      LRF risk by the log-rank test (p=0.017) and in Cox proportional hazards analysis
      (p=0.038). The 5-year OS and DFS rates were 83% and 86% respectively. LVI was
      also significantly associated with OS and DFS in both univariate and multivariate
      analysis. CONCLUSIONS: This series demonstrates a low LRF rate of 7.6% among
      breast cancer patients with node-negative tumors 5 cm and larger after mastectomy
      and adjuvant systemic therapy. Our data indicate that further adjuvant radiation
      therapy to increase local control may not be indicated by tumor size alone in the
      absence of positive lymph nodes. LVI was significantly associated with LRF in our
      series, indicating that patients with this risk factor require careful
      consideration with regard to further local therapy.

PMID- 16887289
TI  - Impact of involved field radiotherapy in partial response after doxorubicin-based
      chemotherapy for advanced aggressive non-Hodgkin's lymphoma.
AB  - PURPOSE: Whether salvage therapy in patients with advanced aggressive non
      Hodgkin's lymphoma (NHL) in partial remission (PR) should consist of radiotherapy
      or autologous stem-cell transplantation (ASCT) is debatable. We evaluated the
      impact of radiotherapy on outcome in PR patients treated in four successive
      European Organization for Research and Treatment of Cancer trials for aggressive
      NHL. PATIENTS AND METHODS: Records of 974 patients (1980-1999) were reviewed
      regarding initial response, final outcome, and type and timing of salvage
      treatment. After 8 cycles of doxorubicin-based chemotherapy, 227 NHL patients
      were in PR and treated: 114 received involved field radiotherapy, 16 ASCT, 93
      second-line chemotherapy, and 4 were operated. Overall survival (OS) and
      progression-free survival (PFS) after radiotherapy were estimated (Kaplan-Meier
      method) and compared with other treatments (log-rank). Impact on survival was
      evaluated by multivariate analysis (Cox proportional hazards model). RESULTS: The
      median PFS in PR patients was 4.2 years and 48% remained progression-free at 5
      years. Half of the PR patients converted to a complete remission. After
      conversion, survival was comparable to patients directly in complete remission.
      Radiotherapy resulted in better OS and PFS compared with other treatments,
      especially in patients with low to intermediate International Prognostic Index
      score, bulky disease, or nodal disease only. Correction by multivariate analysis
      for prognostic factors such as stage, bulky disease, and number of extranodal
      locations showed that radiotherapy was clearly the most significant factor
      affecting both OS and PFS. CONCLUSION: This retrospective analysis demonstrates
      that radiotherapy can be effective for patients in PR after fully dosed
      chemotherapy; assessment in a randomized trial (radiotherapy vs. ASCT) is
      justified.

PMID- 16887291
TI  - Using decision analysis to determine the cost-effectiveness of intensity
      modulated radiation therapy in the treatment of intermediate risk prostate
      cancer.
AB  - BACKGROUND: The specific aim of this study is to evaluate the cost-effectiveness
      of intensity-modulated radiation therapy (IMRT) compared with three-dimensional
      conformal radiation therapy (3D-CRT) in the treatment of a 70-year-old with
      intermediate-risk prostate cancer. METHODS: A Markov model was designed with the
      following states; posttreatment, hormone therapy, chemotherapy, and death.
      Transition probabilities from one state to another were calculated from rates
      derived from the literature for IMRT and 3D-CRT. Utility values for each health
      state were obtained from preliminary studies of preferences conducted at Fox
      Chase Cancer Center. The analysis took a payer's perspective. Expected mean
      costs, cost-effectiveness scatterplots, and cost acceptability curves were
      calculated with commercially available software. RESULTS: The expected mean cost
      of patients undergoing IMRT was $47,931 with a survival of 6.27 quality-adjusted
      life years (QALYs). The expected mean cost of patients having 3D-CRT was $21,865
      with a survival of 5.62 QALYs. The incremental cost-effectiveness comparing IMRT
      with CRT was $40,101/QALYs. Cost-effectiveness acceptability curve analysis
      revealed a 55.1% probability of IMRT being cost-effective at a $50,000/QALY
      willingness to pay. CONCLUSION: Intensity-modulated radiation therapy was found
      to be cost-effective, however, at the upper limits of acceptability. The results,
      however, are dependent on the assumptions of improved biochemical disease-free
      survival with fewer patients undergoing subsequent salvage therapy and improved
      quality of life after the treatment. In the absence of prospective randomized
      trials, decision analysis can help inform physicians and health policy experts on
      the cost-effectiveness of emerging technologies.

PMID- 16887290
TI  - Evaluation of an infrared camera and X-ray system using implanted fiducials in
      patients with lung tumors for gated radiation therapy.
AB  - PURPOSE: To report on the initial clinical use of a commercially available system
      to deliver gated treatment using implanted fiducials, in-room kV X-rays, and an
      infrared camera tracking system. METHODS AND MATERIALS: ExacTrac Adaptive Gating
      from BrainLab is a localization system using infrared cameras and X-rays. Gating
      signals are the patient's breathing pattern obtained from infrared reflectors on
      the patient. kV X-rays of an implanted fiducial are synchronized to the breathing
      pattern. After localization and shift of the patient to isocenter, the breathing
      pattern is used to gate the radiation. Feasibility tests included localization
      accuracy, radiation output constancy, and dose distributions with gating.
      Clinical experience is reported on treatment of patients with small lung lesions.
      RESULTS: Localization accuracy of a moving target with gating was 1.7 mm. Dose
      constancy measurements showed insignificant change in output with gating.
      Improvements of dose distributions on moving targets improved with gating. Eleven
      patients with lung lesions were implanted with 20 mmx0.7 mm gold coil (Visicoil).
      The implanted fiducial was used to localize and treat the patients with gating.
      Treatment planning and repeat computed tomographic scans showed that the change
      in center of gross target volume (GTV) to implanted marker averaged 2.47 mm due
      in part to asymmetric tumor shrinkage. CONCLUSION: ExacTrac Adaptive Gating has
      been used to treat lung lesions. Initial system evaluation verified its accuracy
      and usability. Implanted fiducials are visible in X-rays and did not migrate.

PMID- 16887292
TI  - Two-field versus three-field irradiation technique in the postoperative treatment
      of head-and-neck cancer.
AB  - PURPOSE: We have increasingly used a two-field noncoplanar "caudal tilt"
      technique (CTT) for irradiating postlaryngectomy and pharyngectomy patients to
      avoid matchline problems that can be encountered with the classic three-field
      head-and-neck radiation technique (3FT). This report compares the clinical
      outcomes of patients treated with postoperative radiation (PORT) using either 3FT
      or CTT. METHODS AND MATERIALS: We conducted a retrospective review of the medical
      records of all patients with laryngeal or hypopharyngeal cancers consecutively
      treated with PORT between 1997 and 2002. Three-dimensional dosimetric planning
      was carried out for all patients. RESULTS: Of 91 patients, 39 were treated with
      3FT and 52 with CTT. The median follow-up was 34 months. Estimated rates of 2
      year locoregional control, disease-free survival, and overall survival for
      patients treated with 3FT and CTT were, respectively, 92% and 85% (p=0.241), 62%
      and 55% (p=0.497), and 77% and 72% (p=0.616). There were no significant
      differences in the incidence of acute or late side effects in the two groups.
      CONCLUSIONS: "Caudal tilt" technique is often used as an alternative to 3FT for
      postoperative radiotherapy in cases of greater medical and technical complexity.
      Despite its use in more challenging cases, CTT provides similar long-term
      clinical outcomes compared with standard 3FT, when computerized three-dimensional
      dosimetry is used to assure adequate dosimetry throughout the treated volume.

PMID- 16887293
TI  - Second malignancies after prostate brachytherapy: incidence of bladder and
      colorectal cancers in patients with 15 years of potential follow-up.
AB  - PURPOSE: To report the incidence of second bladder and colorectal cancers after
      prostate brachytherapy. METHODS AND MATERIALS: This review included 125 patients
      treated with I-125 brachytherapy alone, and 223 patients who received
      supplemental external beam radiation therapy. Median follow-up was 10.5 years.
      Patients were followed for the development of lower genitourinary and colorectal
      cancers. Second malignancies arising five years after radiation therapy were
      defined as being potentially associated with treatment; observed rates were then
      compared with age-matched expected rates according to Surveillance, Epidemiology,
      and End Results data. RESULTS: Five years out of treatment, there were 15
      patients with a second solid tumor, including bladder cancer (n = 11), colorectal
      cancer (n = 3), and prostatic urethra cancer (n = 1). The incidence of second
      malignancy was no different in patients treated with brachytherapy alone (1.6%)
      vs. those receiving external beam radiotherapy (5.8%, p = 0.0623). There were
      more observed bladder cancers compared with those expected (relative risk, 2.34,
      95% confidence interval 0.96-3.72; absolute excess risk 35 cancers per 10,000
      patients). Relative risk did not significantly change over increasing follow-up
      intervals up to 20 years after treatment. CONCLUSIONS: There may be an increased
      but small risk of developing a second malignancy after radiation therapy for
      prostate cancer. This outcome could be related to radiation carcinogenesis, but
      more vigilant screening and thorough workup as a result of radiation side effects
      and predisposing conditions (e.g., genetic and environmental factors) in many of
      the patients found to have second malignancies likely contributed to the higher
      number of observed malignancies than expected.

PMID- 16887294
TI  - Long-term toxicity of an intraoperative radiotherapy boost using low energy X
      rays during breast-conserving surgery.
AB  - PURPOSE: Intraoperative radiotherapy (IORT) as a boost for breast cancer delivers
      a high single dose of radiation to a late-reacting tissue; therefore late
      toxicity is of particular interest, and long-term follow-up is warranted. To date
      there are only limited data available on breast cancer patients treated with IORT
      using low energy X-rays. We analyzed toxicity and cosmesis after IORT as a boost
      with a minimum follow-up of 18 months. METHODS AND MATERIALS: A total of 73
      patients treated with IORT (20 Gy/50 kV X-rays; INTRABEAM [Carl Zeiss Surgical,
      Oberkochen, Germany]) to the tumor bed during breast-conserving surgery as a
      boost followed by whole-breast radiotherapy (WBRT, 46 Gy) underwent a
      prospective, predefined follow-up (median, 25 months; range 18-44 months),
      including clinical examination and breast ultrasound at 6-months and
      mammographies at 1-year intervals. Toxicities were documented using the common
      toxicity criteria (CTC)/European Organization for Research and Treatment of
      Cancer and the LENT-SOMA score. Cosmesis was evaluated with a score from 1 to 4.
      RESULTS: The IORT in combination with WBRT was well tolerated, with no Grade 3 or
      4 skin toxicities and no telangiectasias. Fibrosis of the entire breast was
      observed in 5% of the patients. A circumscribed fibrosis around the tumor bed was
      palpable in up to 27% with a peak around 18 months after therapy and a decline
      thereafter. The observed toxicitiy rates were not influenced by age, tumor stage,
      or systemic therapy. The cosmetic outcome was good to excellent in>or=90% of
      cases. CONCLUSIONS: After IORT of the breast using low-energy X-rays, no
      unexpected toxicity rates were observed during long-term-follow-up.

PMID- 16887295
TI  - Low-dose rate prostate brachytherapy is well tolerated in patients with a history
      of inflammatory bowel disease.
AB  - PURPOSE: We report on the follow-up of 24 patients with a prior history of
      inflammatory bowel disease (IBD) treated with brachytherapy for early-stage
      prostate cancer. METHODS AND MATERIALS: Twenty-four patients with a history of
      inflammatory bowel disease (17 with ulcerative colitis (UC), 7 with Crohn's
      disease [CD]) underwent prostate brachytherapy between 1992 and 2004. Fifteen
      patients were treated with I-125 implantation and 6 patients were treated with Pd
      103 alone or in combination with 45 Gy external beam radiation. Charts were
      reviewed for all patients, and all living patients were contacted by phone.
      National Cancer Institute common toxicity scores for proctitis were assigned to
      all patients. Actuarial risk of late toxicity was calculated by the Kaplan-Meier
      method. Statistical analysis was performed using SPSS software. Follow-up ranged
      from 3 to 126 months (median, 48.5 months; mean, 56.8 months). RESULTS: None of
      the patients experienced Grade 3 or 4 rectal toxicity. Four patients experienced
      Grade 2 late rectal toxicity. The 5-year actuarial freedom from developing late
      Grade 2 rectal toxicity was 81%. At a median follow-up of 48.5 months, 23
      patients were alive and had no evidence of disease with a median prostate
      specific antigen for the sample of 0.1 ng/mL (range, <0.05-0.88 ng/mL). One
      patient died of other causes unrelated to his prostate cancer. CONCLUSIONS:
      Prostate brachytherapy is well tolerated in patients with a history of controlled
      IBD. Therefore, brachytherapy should be considered a viable therapeutic option in
      this patient population.

PMID- 16887296
TI  - Constituents of the flowers of Punica granatum.
AB  - A new polyphenol compound named pomegranatate (1), together with, ellagic acid,
      3,3',4'-tri-O-methylellagic acid, ethyl brevifolincarboxylate, urolic and
      maslinic acids, and daucosterol were isolated from the ethanolic extract of the
      flowers of Punica granatum. The structure of compound 1 was determined by
      spectroscopic analysis. Maslinic acid exhibited antioxidant activity, evaluated
      by measurement of LDL susceptibility to oxidation.

PMID- 16887297
TI  - Cytotoxic constituents from Anagyris foetida leaves.
AB  - Anagyris foetida extracts were investigated in preliminary cytotoxic tests
      against two tumour cell lines. Chromatographic separations on active extracts led
      to the isolation of two alkaloids, anagyrine (1) and baptifoline (2), as well of
      isorhamnetin (3) and syringin 4-O-beta-D-glucopyranoside (4). In vitro
      cytotoxicity of compounds 1-3 was also evaluated.

PMID- 16887298
TI  - Structural organization and expression of human MTUS1, a candidate 8p22 tumor
      suppressor gene encoding a family of angiotensin II AT2 receptor-interacting
      proteins, ATIP.
AB  - The Mitochondrial Tumor suppressor 1 (MTUS1) gene is a newly identified candidate
      tumor suppressor gene at chromosomal position 8p22. We report here that MTUS1
      encodes a family of proteins whose leader member (ATIP1) was previously isolated
      in our laboratory as a novel interacting partner of the angiotensin II AT2
      receptor involved in growth inhibition (Nouet, JBC 279: 28989-97, 2004). The
      MTUS1 gene contains 17 coding exons distributed over 112 kb of genomic DNA.
      Alternative exon usage generates three major transcripts (ATIP1, ATIP3 and
      ATIP4), each showing different tissue distribution. ATIP polypeptides are
      identical in their carboxy-terminal region carrying four coiled-coil domains. In
      their amino-terminal portion, ATIP polypeptides exhibit distinct motifs for
      localisation in the cytosol, nucleus or cell membrane, suggesting that MTUS1 gene
      products may be involved in a variety of intracellular functions in an AT2
      dependent and independent manner. ATIP1 is ubiquitous and highly expressed in the
      brain. ATIP3 is the major transcript in tissues (prostate, bladder, breast,
      ovary, colon) corresponding to cancer types with frequent loss of heterozygosity
      at 8p22. Interestingly, ATIP4 is a brain-specific transcript highly abundant in
      the cerebellum and fetal brain. High evolutionary conservation of ATIP amino-acid
      sequences suggests important biological roles for this new family of proteins in
      tumor suppression and/or brain function.

PMID- 16887299
TI  - Long-term consequences of early nutrition.
AB  - Nutritional and metabolic exposure during critical periods of early human
      development can have a long-term programming effect on health in adulthood. This
      is supported by evidence from epidemiological studies, numerous animal models and
      clinical intervention trials. An improved understanding of the mechanisms and
      effects of metabolic programming has the potential to contribute significantly to
      the prevention of some major health risks. Obesity and the metabolic syndrome,
      whose prevalences increase in almost all countries of the world, may have partly
      developmental origins. Collaboration of clinicians, epidemiologists and basic
      scientists in an EU funded research project on the relationship between early
      nutrition and later health (The EU Early Nutrition Programming Project,
      www.metabolic-programming.org) should provide further insights into metabolic
      programming and help to transfer scientific progress into clinical practice.

PMID- 16887300
TI  - Lead-induced apoptosis in PC 12 cells: involvement of p53, Bcl-2 family and
      caspase-3.
AB  - It has been reported that lead could induce apoptosis in a variety of cell types.
      Although mitochondrion is regarded as the most pertinent pathway in mediating
      apoptosis, the exact mechanisms of lead-induced apoptosis are still largely
      unknown. Furthermore, there is little information about expressions and
      regulations of Bax, Bcl-2, and p53 in lead-induced apoptosis, which are critical
      regulators of mitochondrial stability. The present study was undertaken to
      determine whether lead could induce DNA damage and apoptosis in PC 12 cells, and
      the involvement of Bax, Bcl-2, p53, and caspase-3 in this process. The results
      showed that lead could induce DNA damage and apoptosis in PC 12 cells,
      accompanying with upregulation of Bax and downregulation of Bcl-2. Additionally,
      the expression of p53 increased, and caspase-3 was activated. Therefore, it
      suggests that lead can induce activation of p53 by DNA damage, which may lead to
      imbalance of Bax/Bcl-2 and mitochondrial dysfunction. Subsequently, after
      activation of caspase-3, lead-induced apoptosis occurres.

PMID- 16887301
TI  - Tibolone (Livial) enhances warfarin-induced anticoagulation in postmenopausal
      women.
AB  - OBJECTIVE: To investigate the potential drug interaction between tibolone and
      warfarin in healthy postmenopausal women. METHODS AND RESULTS: The study was
      designed as a double-blind, randomized, placebo-controlled, two-way crossover
      study in postmenopausal women. After stabilization of the International
      Normalized Ratio (INR; a standardized prothrombin time, PT) between 1.4 and 2.0
      with warfarin, subjects were randomized to receive either tibolone (2.5mg/day) or
      placebo for 21 days. After a 7-day wash-out period (during which warfarin
      treatment was continued) the treatments were crossed over. Primary efficacy
      parameters were INR and coagulation Factors II, VII, VIIa and X (means of
      measurements at Days 18 and 20 and Days 46 and 48). Treatment with tibolone
      induced a statistically significant increase in INR (estimate of mean
      difference=0.40; P=0.002), and a statistically significant decrease in
      coagulation factors. Treatments were generally well tolerated and no clinically
      significant adverse events were observed. CONCLUSIONS: Tibolone enhances warfarin
      induced anticoagulation in postmenopausal women, as reflected by increases in INR
      and decreases in coagulation Factors II, VII, VIIa and X, compared to placebo. It
      is advisable to monitor for changes in coagulation status during (and after
      discontinuation of) simultaneous use of tibolone and warfarin.

PMID- 16887302
TI  - In situ coating--an approach for particle modification and encapsulation of
      proteins during spray-drying.
AB  - In this paper, we present a method for in situ coating of individual protein
      particles in a respirable size. The aim of the coating was to influence the
      particle/powder properties, and to reduce or prevent surface-induced
      conformational changes of the protein, during spray-drying, which was the method
      used for simultaneously preparing and coating particles. The investigated
      formulations included bovine serum albumin (BSA), trehalose and either of the two
      non-ionic polymers, hydroxypropyl methylcellulose (HPMC) and poly(ethylene oxide)
      poly(propylene oxide) triblock co-polymer (Poloxamer 188). Complete protein
      coating as measured by electron spectroscopy for chemical analysis (ESCA) was
      achieved at a polymer concentration of approximately 1% of the total solids
      weight, and could be predicted from the dynamic surface tension at the air/water
      interface, as measured by the pendant drop method. Further, particle properties
      such as: size, dissolution time, powder flowability, and apparent particle
      density, as measured by gas pycnometry, were affected by the type and
      concentration of the polymer. In addition, the particle surface morphology could
      possibly be correlated to the surface elasticity of the droplet surface during
      drying. Moreover, an extensive investigation (Fourier transform infrared
      spectroscopy, circular dichroism and size exclusion chromatography) of the
      structural effects of protein encapsulated in a polymeric coating suggested that
      in situ coating provide particulate formulations with preserved native
      conformation and with a high stability during rehydration.

PMID- 16887303
TI  - PLA/PLGA nanoparticles for sustained release of docetaxel.
AB  - This study investigates the potentiality of nanosphere colloidal suspensions as
      sustained release systems for intravenous administration of docetaxel (DTX).
      Nanospheres were prepared by solvent displacement method using polylactic acids
      (PLA) at different molecular weight and polylactic-co-glycolic (PLGA) as
      biodegradable matrices. The systems were characterized by light scattering
      analysis for their mean size, size distribution and zeta potential and by
      scanning electron microscopy (SEM) for surface morphology. The average diameters
      of the nanoparticles ranged from 100 to 200 nm. Negative zeta potential values
      were observed for all systems, particularly the nanospheres produced with the
      lowest molecular weight PLA showed a zeta potential value of -28mV. Differential
      scanning calorimetry analysis (DSC) suggested that DTX was molecularly dispersed
      in the polymeric matrices. A biphasic release of DTX was observed for all
      colloidal suspensions, after a burst effect in which about 50% (w/w) of the
      loaded drug was released a sustained release profile for about 10 days was
      observed. To evaluate the influence of the polymeric carrier on the interaction
      of DTX with biological membranes, we performed an in vitro study using lipid
      vesicles made of dipalmitoylphosphatidylcholine (DPPC) as a biomembrane model.
      DSC was used as a simple and not invasive technique of analysis. DTX produced a
      depression of DPPC pretransition peak, no variation of the main phase transition
      temperature and a significative increase of DeltaH value, showing a superficial
      penetration of the drug into DPPC bilayer. Kinetic experiments demonstrated that
      the release process of DTX form nanospheres is affected by the molecular weight
      of the employed polymers.

PMID- 16887304
TI  - The role of monocarboxylate transporters in uptake of lactic acid in HeLa cells.
AB  - This study was aimed to identify the monocarboxylate transporters (MCTs) in HeLa
      cells and to delineate their role in transportation of L-lactic acid. The
      functional role of MCTs in lactic acid transport was evaluated at various mucosal
      pHs (4.5-7.4) or in the presence of various loading doses (0.2-2mM) of lactic
      acid, MCT substrates (nicotinic acid, n-butyric acid, etc.) and inhibitors (alpha
      cyano-4-hydroxycinnamate and para-chloromercuribenzoic acid). The molecular
      properties of MCTs were characterized using reverse transcription-polymerase
      chain reaction (RT-PCR). The uptake rate of lactic acid by HeLa cells
      significantly increased from 0.353+/-0.052 to 1.103+/-0.196 micromol/mg protein
      as the extra-cellular pH changed from 7.4 to 4.5, indicating that activities of
      MCT were mediated through H(+)-linked mechanism. The uptake profile of lactic
      acid followed the saturable process with the K(m) value of 0.53 mM. The uptake
      rate of lactic acid is concentration dependent and is reduced in the presence of
      MCT inhibitors. MCT isoforms 1, 5 and 6 in HeLa cells were identified by RT-PCR.
      HeLa cell line can be used as an effective screening tool for intravaginally
      administered drugs targeted toward MCT.

PMID- 16887305
TI  - Volterra Slice otoacoustic emissions recorded using maximum length sequences from
      patients with sensorineural hearing loss.
AB  - When normally hearing ears are stimulated with maximum length sequences (MLS) of
      clicks, a family of non-linear temporal interaction components of otoacoustic
      emissions (OAEs) can be derived, which have been named Volterra Slice OAEs (VS
      OAEs). This study investigates the sensitivity of VS OAEs to sensorineural
      hearing impairment in adults, compared to that of the widely used derived non
      linear click evoked OAE (DNL CEOAE). VS OAEs and DNL CEOAEs were obtained from 24
      normally hearing and 24 hearing impaired ears using a custom-built MLS system and
      a Otodynamics 'ILO88' OAE Analyzer, respectively. The results show that, based on
      waveform reproducibility, VS OAEs are as successful as DNL CEOAEs at separating
      normal from impaired ears at the audiometric frequencies of 1 and 2 kHz, where a
      strong correlation is found between the amplitudes of the two OAE types. At 4 kHz
      however, VS OAEs are a significantly better indicator of hearing loss than DNL
      CEOAEs. This difference at 4 kHz appears to be due to the lack of stimulus
      artefact contamination of VS OAEs in the early, high frequency portion of the
      response. The findings suggest that VS OAEs may provide a better diagnostic and
      monitoring tool for hearing loss at high frequencies than the conventional DNL
      CEOAE.

PMID- 16887306
TI  - A new spontaneous mutation in the mouse protocadherin 15 gene.
AB  - We have characterized a new allele of the protocadherin 15 gene
      (designatedPcdh15(av-6J)) that arose as a spontaneous, recessive mutation in the
      C57BL/6J inbred strain at Jackson Laboratory. Analysis revealed an inframe
      deletion in Pcdh15, which is predicted to result in partial deletion of cadherin
      domain (domain 9) in Pcdh15. Morphologic study revealed normal to moderately
      defective cochlear hair cell stereocilia in Pcdh15(av-6J) mutants at postnatal
      day 2 (P2). Stereocilia abnormalities were consistently present at P5 and P10.
      Degenerative changes including loss of inner and outer hair cells were seen at
      P20, with severe sensory cell loss in all cochlear turns occurring by P40. The
      hair cell phenotype observed in the 6J allele between P0 and P20 is the least
      severe phenotype yet observed in Pcdh15 alleles. However, young Pcdh15(av-6J)
      mice are unresponsive to auditory stimulation and show circling behavior
      indicative of vestibular dysfunction. Since these animals show severe functional
      deficits but have relatively mild stereocilia defects at a young age they may
      provide an appropriate model to test for a direct role of Pcdh15 in
      mechanotransduction.

PMID- 16887307
TI  - Evaluation of the mouse model for acute otitis media.
AB  - Various animal models have been employed for otitis media research. The mouse has
      been studied less, in spite of its many advantages. To better understand the
      suitability of the mouse for studies of otitis media, an evaluation was made of
      its middle ear inflammatory processes following inoculation with heat-killed
      Streptococcus pneumoniae (strain 6A), one of the three most common bacteria to
      cause otitis media in the human. A total of 94 BALB/c mice were injected
      transtympanically with three concentrations of heat-killed bacteria (10(4),
      10(6), and 10(9) organisms per ml) and inflammation evaluated with both
      histologic examination and auditory brainstem response audiometry. Dose-related
      measures of the time course of inflammation showed it was maximal at 3 days. PBS
      injected control mice also demonstrated some degree of middle ear inflammation.
      Therefore, inflammation measures from PBS injected mice were used as the
      threshold above which histologic inflammatory changes would be considered a
      response to bacteria. These quantitative comparisons of bacterial and PBS
      inoculations revealed the most significant middle ear measures of inflammation
      were amount of fluid in the middle ear, tympanic membrane thickness, and number
      of inflammatory cells. The induction of middle ear inflammation in the mouse
      demonstrated the applicability of this model for investigations of otitis media.

PMID- 16887308
TI  - Comparison between lung weight and blood strontium in bodies found in seawater.
AB  - This paper examines the use of lung weight increase as an indicator of seawater
      drowning compared to the amount of Sr absorbed by the blood. The study population
      was limited to male victims older than 20 years. Significant differences between
      cases of drowning and "non-drowning" were detected in terms of the lung-heart
      weight ratio (L/H) (p<0.001) or lung-body weight ratio (L/B) (p=0.005). However,
      using lung weight (L), L/H or L/B to distinguish between seawater drownings and
      saltwater non-drownings some overlap was produced. The factor rendering least
      overlap was L/B, which also appeared to be non-dependent on the victim's age. Our
      findings suggest that a value of L/B higher than 19.5 g/kg could be a useful
      indicator of death by drowning, but that when a lower value is found, additional
      drowning diagnoses would be needed to establish the manner of death.

PMID- 16887309
TI  - Max Frei theory revisitation: does really strokes depth change along time?
AB  - A serious problem in questioned document examination is to establish the age of
      written lines. With respect to paper dating, in the past, Max Frei theory (based
      only on microscope analysis) claimed that strokes are time-dependent. Therefore,
      according to this theory, it has been asserted that from the analysis of the
      strokes depth changes it is possible to try to date the handwritten document (to
      find out that the document is older than ...). In the present work, we
      investigate the strokes depth change by a laser profilometer considering not only
      the time but also microclimatic variations. First, we analyze the stability of
      stroke characteristics along the time. In particular, we demonstrate that if the
      document is preserved without change of temperature and humidity, the depth of
      the strokes has not appreciable changes. In this way, we have the purpose to
      verify the real possibility of documents dating by means of Max Frei theory.
      Subsequently, we test how the 3D profile of strokes changes in connection with
      the microclimatic variations. In particular, we test humidity variations. With
      this experiment, we show that humidity variations reduce the strokes depth.
      Moreover, this effect shows a non-linear trend, leaving a hysteresis on the
      depth. Finally, we show that the analysis of 3D stroke profile is unable to
      determine the age of documents.

PMID- 16887311
TI  - Will genetic polymorphism of tetranucleotide sequences help in the diagnostics of
      major psychiatric disorders?
AB  - Expecting a significant breakthrough in the diagnosis of complex disorders of
      neuropsychiatric background, intensive efforts are taking place to establish
      genetic markers correlated with these disorders. During the last decade, this
      research was focused on code regions connected with neurotransmission and
      metabolism of catecholamines. Nowadays big diagnostic expectations are associated
      with sequences of STR type, which are widespread throughout the genome. These
      microsatellite sequences do not code proteins, but may have function of
      regulatory elements in the process of gene transcription and expression. One of
      these is polymorphic TH01 locus with TCAT tetranucleotide repetitive motive. It
      is located in chromosomal position 11p15 in the first intron of the tyrosine
      hydroxylase gene (TH). We examined the existence of the association between
      polymorphism of TH01 marker and schizophrenia. The results of statistical
      comparative analysis between neuropsychiatric patients from Poland and their
      regionally matched healthy subjects were presented.

PMID- 16887310
TI  - Myocardial Cx43 expression in the cases of sudden death due to dilated
      cardiomyopathy.
AB  - PURPOSE: Probing into myocardial connexin (Cx) 43 expression in the cases of
      sudden death due to dilated cardiomyopathy (DCM) and relationship between Cx43
      expression and sudden death. METHOD: Myocardial Cx43 was detected with
      immunohistochemical staining in the cases of 11 sudden death caused by DCM and 14
      cases of control group who died of violent reasons and other diseases, which were
      autopsied in our department from 1997 to 2003. RESULT: Of 11 cases of DCM, there
      were 10 men and 1 woman with ranging in age from 7 to 49 years old (x (37.8)
      years old for 9 adult cases). Of 14 cases in the control group, there were 10 men
      and 4 women with ranging in age from 11 to 53 years old (x (29.9) years old for
      11 adult cases). Myocardial Cx43 expression was obviously decreased in DCM group.
      Positive dyeing spots were different in size, distribution, color and disparity,
      some of them were distributed in the form of particle. Obvious change had not
      been observed in the cases of control group or with only slight changes in
      coloring degree and expressive area. The quantitative data showed that there was
      significant difference between two groups (p=0.0075) about Cx43 expressive area,
      but there was no difference between the left and right ventricles (p>0.05) in
      each group itself. And there was not difference between the two groups about
      average optical density of expression. CONCLUSION: Myocardial Cx43 expression is
      obviously reduced in the patients with DCM who die suddenly. The alteration of
      quantity and distribution of myocardial Cx43 expression is probably related to
      sudden death of the patients with DCM.

PMID- 16887312
TI  - Acoustic parameters of snoring sound to assess the effectiveness of the Muller
      Manoeuvre in predicting surgical outcome.
AB  - OBJECTIVE: To assess the effectiveness of the Muller Manoeuvre in predicting
      surgical outcome in non-apnoeic snorers. METHODS: Forty-one non-apnoeic snorers
      performed the Muller Manoeuvre, prior to palatal surgery for snoring. Pre
      operatively and between 1.0 and 4.1 months (mean 2.5 months) post-operatively,
      patients were admitted overnight when their sleeping position and snoring sounds
      were recorded. At the time of the post-operative recordings, patients were
      required to complete a specifically designed questionnaire. Snore files
      comprising the inspiratory component of the first 100 snores whilst the patient
      was supine, were extracted. Snore duration (s), snore loudness (dBA), snore
      periodicity (%) and the energy ratios for the frequency bands 0-200, 0-250 and 0
      400 Hz were calculated. Only patients who showed improvements in snore
      periodicity and all energy ratios were considered to be surgical successes. In
      addition, patients were also categorised as 'successes' or 'failures' depending
      on their responses to specific questionnaire questions. The effectiveness of the
      Muller Manoeuvre in predicting surgical outcome was then tested using these
      categories. RESULTS: The 41 patients included 35 men and 6 women. Mean age: 47
      years (24-67 years). Mean PNIFR 145 (80-230). Median reported alcohol intake was
      11-15 units/week (0 to 26-30 units/week). Mean BMI: 30.6 kg/m2 (24.3-47.2 kg/m2).
      Twenty-four patients underwent an uvulopalatal elevation palatoplasty and
      seventeen a traditional palatoplasty. Following the Muller Manoeuvre, patients
      were categorised as 'ideal', 'suboptimal, but acceptable' or 'unsuitable' for
      surgery. Using the acoustic parameters, 23/41 patients were considered a surgical
      success, whilst 18/41 were considered failures. Using the questionnaire
      responses, 14/40 patients were considered a surgical success, whilst 26/40 were
      considered failures. There was no correlation between the subjective and
      objective outcomes (rho=0.193; p=0.227). Neither pre-operative BMI, type of
      palatoplasty performed, patient gender, age, PNIFR or reported alcohol intake
      were confounders of surgical outcome. For patients considered 'ideal' and
      'suboptimal, but acceptable', using acoustic outcomes, the Muller Manoeuvre had a
      specificity of 55.5% and a sensitivity of 30.4%, compared with a sensitivity of
      57.7% and a specificity of 28.6% when questionnaire responses were used. If only
      patients considered 'ideal' were considered, the specificity was 66.7%, and the
      sensitivity 21.7% when using acoustic outcomes, compared with a sensitivity of
      69.2% and a specificity of 78.6% when questionnaire responses were used.
      CONCLUSION: The Muller Manoeuvre appears to have no role in the pre-operative
      assessment of palatal surgery for non-apnoeic snorers.

PMID- 16887313
TI  - Diagnostic value of multislice computed tomography angiography in coronary artery
      disease: a meta-analysis.
AB  - PURPOSE: To perform a meta-analysis of the diagnostic value of multislice CT
      (MSCT) angiography in the detection of coronary artery disease (CAD) when
      compared to conventional coronary angiography. MATERIALS AND METHODS: A search of
      PubMed and MEDLINE databases for English literature was performed. Only studies
      with at least 10 patients comparing MSCT angiography with conventional coronary
      angiography in the detection of CAD were included. Diagnostic value of MSCT
      angiography compared to coronary angiography was compared and analyzed at segment
      , vessel- and patient-based assessment. RESULTS: 47 studies (67 comparisons) met
      the criteria and were included in our study. Pooled overall sensitivity,
      specificity and 95% confidence interval for MSCT angiography in the detection of
      CAD were 83% (79%, 89%), 93% (91%, 96%) at segment-based analysis; 90% (87%,
      94%), 87% (80%, 93%) at vessel-based analysis; and 91% (88%, 95%), 86% (81%, 92%)
      at patient-based analysis, respectively. Diagnostic accuracy of MSCT angiography
      in evaluating assessable segments was significantly improved with 64-slice
      scanners when compared to that with 4- and 16-slice scanners (p<0.05).
      CONCLUSION: Our meta-analysis showed that MSCT angiography has potential
      diagnostic accuracy in the detection of CAD. Diagnostic performance of MSCT
      angiography has been significantly improved with the latest 64-slice CT, with
      resultant high qualitative and quantitative diagnostic accuracy. 16-slice CT was
      limited in spatial resolution which makes it difficult to perform quantitative
      assessment of coronary artery stenoses.

PMID- 16887314
TI  - Paget's disease of the breast: clinical, mammographic, sonographic and pathologic
      findings in 52 cases.
AB  - PURPOSE: To determine and quantitate radiologic characteristics of Paget's
      disease of the breast and to report clinical and pathologic findings. MATERIALS
      AND METHODS: A retrospective review of records of 2872 women who received a
      diagnosis of breast carcinoma between January 1988 and January 2006 revealed 52
      histologically proved Paget's disease of the breast. Analysis included history,
      findings at physical examination, mammography and sonography (US) and histologic
      type of Paget's disease. RESULTS: At physical examination, palpable mass (n=33,
      63%), nipple erythema-eczema-ulceration (n=17, 33%) and blood-stained nipple
      discharge (n=5, 10%) were noted. Among 17 patients who had clinically evident
      Paget's disease, the mammographic findings were isolated microcalcifications in 3
      (18%), mass associated with microcalcifications in 5 (29%), mass in 2 (12%) and
      negative in 7 (41%) patients. In the 35 patients with clinically inevident
      Paget's disease, these mammographic findings were 43% (n=15), 34% (n=12), 20%
      (n=7) and 3% (n=1), respectively. US depicted 43 masses in 35 patients, all of
      which were lobulated or irregularly contoured, mostly (n=41, 95%) without
      posterior acoustic shadowing. The cancer was clinically occult in 10% (n=5),
      mammographically occult in 15% (n=8) and radiologically occult in 13% (n=7) of
      the 52 patients. Histologically, the tumor was multifocal and/or multicentric in
      11 (21%) patients. CONCLUSION: The clinical features of Paget's disease are
      characteristic and should alert the clinician to the likelihood of an underlying
      carcinoma, which should be evaluated radiologically. However, as Paget's disease
      is primarily a clinical diagnosis and mammograms may be negative, screening
      programs without clinical examination may result with delay in diagnosis. As a
      result, both clinical and imaging findings are complementary and should be
      correlated to confirm or exclude a diagnosis of Paget's disease.

PMID- 16887316
TI  - High throughput HPLC-ESI-MS method for the quantitation of dexamethasone in blood
      plasma.
AB  - Dexamethasone is a synthetic glucocorticoid with potent anti-inflammatory
      properties. However, its administration causes significant side effects,
      specially in long-term therapy. A new approach for limiting adverse effects
      consists in the slow and constant deliver of this drug, using dexamethasone-21
      phosphate-loaded erythrocytes (RBC) as circulating bioreactors converting the non
      diffusible dexamethasone-21-phosphate into the diffusible dexamethasone. In order
      to evaluate the real possibility to use this new method of administration, a
      simple, cheap and rapid assay was set to manage a large number of samples
      originating from clinical studies. Due to the sample complexity and analite
      polarity, electrospray mass spectrometry (MS) is the most powerful technique to
      achieve qualitative and quantitative data. In order to overcome the complex, time
      consuming and expensive LC-MS/MS methods reported in the literature in the
      present work a standard fluxes HPLC-ESI-MS method was set up for quantitative
      evaluation of dexamethasone. Thanks to the extraction ion chromatogram (XIC)
      feature of the software, it was possible to obtain sharp profiles for
      dexamethasone (DXM) and for the employed internal standard (IS) flumethasone
      (FM), in spite of the extremely complicated chromatogram obtained after HPLC
      separation of acetonitrile extracted plasma sample, thus avoiding the use of the
      expensive deuterated internal standard. This enabled us to obtain a linear
      response curve, allowing the quantification of DXM from blood samples at the
      picomoles level.

PMID- 16887315
TI  - Advantages of using tetrahydrofuran-water as mobile phases in the quantitation of
      cyclosporin A in monkey and rat plasma by liquid chromatography-tandem mass
      spectrometry.
AB  - A new analytical method is described here for the quantitation of anti
      inflammatory drug cyclosporin A (CyA) in monkey and rat plasma. The method used
      tetrahydrofuran (THF)-water mobile phases to elute the analyte and internal
      standard, cyclosporin C (CyC). The gradient mobile phase program successfully
      eluted CyA into a sharp peak and therefore improved resolution between the
      analyte and possible interfering materials compared with previously reported
      analytical approaches, where CyA was eluted as a broad peak due to the rapid
      conversion between different conformers. The sharp peak resulted from this method
      facilitated the quantitative calculation as multiple smoothing and large number
      of bunching factors were not necessary. The chromatography in the new method was
      performed at 30 degrees C instead of 65-70 degrees C as reported previously.
      Other advantages of the method included simple and fast sample extraction-protein
      precipitation, direct injection of the extraction supernatant to column for
      analysis, and elimination of evaporation and reconstitution steps, which were
      needed in solid phase extraction or liquid-liquid extraction reported before.
      This method is amenable to high-throughput analysis with a total chromatographic
      run time of 3 min. This approach has been verified as sensitive, linear (0.977
      4000 ng/mL), accurate and precise for the quantitation of CyA in monkey and rat
      plasma. However, compared with the usage of conventional mobile phases, the only
      drawback of this approach was the reduced detection response from the mass
      spectrometer that was possibly caused by poor desolvation in the ionization
      source. This is the first report to demonstrate the advantages of using THF-water
      mobile phases to elute CyA in liquid chromatography.

PMID- 16887318
TI  - In silico insight into two rice chromosomal regions associated with submergence
      tolerance and resistance to bacterial leaf blight and gall midge.
AB  - Plants respond to both biotic and abiotic stresses through a common signaling
      system to provide defense and protection against many adverse environments. Many
      genes/QTLs governing resistance to both biotic and abiotic stresses have been
      studied and mapped in rice. Sub1, a major QTL for submergence tolerance is
      collocated with a gene Gm1 for gall midge resistance on chromosome 9 (Region 1).
      Likewise a bigger region on chromosome 5 (Region 2) has a minor QTL for
      submergence tolerance collocated with genes for bacterial blight resistance.
      Utilizing the rice sequence and annotation data (TIGR) and rice genome annotation
      project database (RAP-DB), we wanted to know the kinds of genes underlying these
      two chromosomal regions where genes/QTL governing tolerance to both biotic and
      abiotic stresses are collocated. We also analyzed the pattern of distribution of
      these genes across the BAC/PAC clones spanning the region so that candidate genes
      can be short listed for a functional analysis. Genes known to have a role in
      submergence tolerance were present in both the regions. Region 1, had a unique
      transcription factor like trithorax protein, which is a positional candidate gene
      for submergence tolerance. Pyruvate decarboxylase (PDC) gene for alcohol
      fermentation and cation transporting ATPase c-terminal domain are likely
      candidates for submergence QTL in Region 2. Genes such as SKP1 and elicitor
      induced cytochrome p450 associated with tissue necrosis and insect resistance
      were found in region 1. Multiple copies of ORFs for signal transduction proteins,
      transcription factors, genes for systemic acquired resistance, Ubiquitin proteins
      and pathogen elicitor identification and degrading proteins were located as a
      cluster in Region 2, where bacterial blight resistance genes mapped. Validation
      of the data obtained from TIGR with other databases (RAP and KOME) confirmed our
      findings. The functional role of some of the significant candidate genes needs to
      be established. Allele/gene specific markers can then be designed for use in MAS
      thus enhancing durable tolerance/resistance faster.

PMID- 16887317
TI  - A new hydrophilic interaction liquid chromatographic (HILIC) procedure for the
      simultaneous determination of pseudoephedrine hydrochloride (PSH),
      diphenhydramine hydrochloride (DPH) and dextromethorphan hydrobromide (DXH) in
      cough-cold formulations.
AB  - A new HILIC method has been developed for the simultaneous determination of
      pseudoephedrine hydrochloride (PSH), diphenhydramine hydrochloride (DPH) and
      dextromethorphan hydrobromide (DXH) in cough-cold syrup. Mobile phase consists of
      methanol:water (containing 6.0 g of ammonium acetate and 10 mL of triethylamine
      per liter, pH adjusted to 5.2 with orthophosphoric acid), 95:5 (v/v). Column
      containing porous silica particles (Supelcosil LC-Si, 25 cm x 4.6 mm, 5 microm)
      is used as stationary phase. Detection is carried out using a variable wavelength
      UV-vis detector at 254 nm for PSH and DPH, and at 280 nm for DXH. Solutions are
      injected into the chromatograph under isocratic condition at constant flow rate
      of 1.2 mL/min. Linearity range and percent recoveries for PSH, DPH and DXH were
      150-600, 62.5-250, 75-300 microg/mL and 100.7%, 100.1% and 100.8%, respectively.
      Method is stability indicating and excipients like saccharin sodium, sodium
      citrate, flavour and sodium benzoate did not interfere in the analysis. Compounds
      elute in order of increasing ionization degree caused by cation-exchange
      mechanism in a run time of less than 15 min. Mobile phase pH is manipulated to
      regulate ionization and ion-exchange interaction and thereby retention of
      compounds.

PMID- 16887319
TI  - The complexity of patient participation: lessons learned from patients' illness
      narratives.
AB  - OBJECTIVE: To describe the meaning of active participation from the patient's
      perspective. METHODS: We used a narrative framework to analyze transcripts
      generated from 16 qualitative open-ended, semi-structured interviews with primary
      care patients in Houston, Texas. RESULTS: Patients' illness narratives reflected
      several themes related to patient participation. These included patients'
      perspectives of illness (i.e., how central the illness is in the patient's
      overall life story and how changeable the patient believes their illness to be)
      and aspects of actions pursued in the context of patients' illness narratives
      (i.e., the degree of illness-related activity that a patient engages in and the
      role of partnership with the patient's physician in health decision making and
      illness management). The relationships among these themes explained a limited
      number of distinct illness-management strategies pursued by patients. CONCLUSION:
      Our findings revealed a level of complexity to patients' healthcare participation
      that has not been previously described. Patients' illness-management strategies
      were explained by four thematic story elements in dynamic interplay with unique
      variations for each individual. Further research is needed to explore how these
      story elements influence communication between patients and physicians. PRACTICE
      IMPLICATIONS: By understanding the nature of and relationships between the
      thematic elements in patients' illness narratives, practitioners will be able to
      better inform their negotiations with patients regarding participation in
      healthcare.

PMID- 16887321
TI  - Cytoreductive surgery and perioperative intraperitoneal chemotherapy for
      peritoneal carcinomatosis from colorectal carcinoma: non-mucinous tumour
      associated with an improved survival.
AB  - AIMS: Cytoreductive surgery combined with perioperative intraperitoneal
      chemotherapy has been reported as a treatment option for patients with peritoneal
      carcinomatosis from colorectal carcinoma. METHODS: Thirty patients with
      colorectal peritoneal carcinomatosis underwent cytoreductive surgery and
      perioperative intraperitoneal chemotherapy. All appendiceal cancers were
      excluded. All patients were followed until January 2006 or death. Univariate
      analysis was performed to evaluate significant prognostic factors for overall
      survival, defined from the time of surgery. RESULTS: There were 13 male patients.
      The mean age at the time of surgery was 54years. There was no hospital mortality.
      The mean duration of hospital stay was 27days. The overall median survival was
      29months, with 1- and 2-year survival of 72% and 64%, respectively. Twenty-one
      patients had complete cytoreduction and their 1- and 2-year survival rates were
      85% and 71%, respectively. Univariate analysis demonstrated that patients with
      non-mucinous colorectal adenocarcinoma, Peritoneal Cancer Index (PCI) < or =13,
      and complete cytoreduction were associated with an improved survival.
      CONCLUSIONS: This study reported on 30 patients who underwent cytoreductive
      surgery and perioperative intraperitoneal chemotherapy for colorectal peritoneal
      carcinomatosis. Patients with mucinous tumour had relatively more extensive
      intraperitoneal disease. Non-mucinous colorectal adenocarcinoma, PCI < or =13,
      and complete cytoreduction were associated with an improved survival.

PMID- 16887322
TI  - Molecular and pharmacodynamic characteristics of the novel multi-target tumor
      growth inhibitor ZK 304709.
AB  - Loss of cell cycle control and tumor-induced neovascularization are major drivers
      of human tumor growth. The multi-target tumor growth inhibitor ZK 304709 is a
      nanomolar inhibitor of cyclin-dependent kinases 1, 2, 4, 7 and 9, as well as
      vascular endothelial growth factor receptor tyrosine kinase 1-3 and of platelet
      derived growth factor receptor beta tyrosine kinase. The multi-targeted mode of
      action of ZK 304709 acting on cell cycle and angiogenesis resulted in superior
      efficacy compared to standard chemotherapeutic compounds both in s.c. human tumor
      xenografts as well as orthotopic human pancreatic carcinoma models.

PMID- 16887320
TI  - Prognostic significance of total number of nodes removed, negative nodes removed,
      and ratio of positive nodes to removed nodes in node positive breast carcinoma.
AB  - BACKGROUND: This study was undertaken to investigate whether total number of
      nodes (pNtot) removed, negative nodes removed (pNneg), and ratio of positive
      nodes to total nodes removed (pNratio) are predictors of survival in node
      positive patients. STUDY DESIGN: The records of 801 consecutive invasive breast
      cancer patients with T1-3 tumour and positive axillary lymph node who underwent
      modified radical mastectomy in our hospital were reviewed. pNtot and pNneg were
      categorized, and pNratio was computed. The influence of these probable prognostic
      factors on survival was investigated. Survival curves were generated by Kaplan
      Meier method and log-rank test was used for comparisons. Multivariate analyses
      were performed by Cox proportional hazard model. RESULTS: Median pNtot, and pNneg
      are 19 (range 5-54), and 13 (range 0-53), respectively. pNtot>15, and pNneg>15
      were independently associated with reduced hazard ratios (HRs) of 0.62 (CI 0.48
      0.79), and 0.68 (CI 0.52-0.89), respectively. The highest ratio (>0.25) of
      pNratio is associated with the highest hazard ratio for death (HR 3.8, CI 2.74
      5.50) compared to the lowest ratio for death (<0.001). CONCLUSIONS: pNtot, pNneg,
      and pNratio appear prognostic factors for survival in node positive breast
      cancers. Axillary lymph node dissection with more number of nodes removed (>15)
      or negative nodes (>15) are associated with increased survival.

PMID- 16887323
TI  - Dissociation of the component processes of attention in healthy adults.
AB  - Cohen's [Cohen, R. (1993). The Neuropsychology of Attention. New York: Plenum
      Publishing] model of attention proposes four interrelated processes, namely
      Sensory Selective Attention, Response Selection/Control, Focus/Capacity, and
      Sustained Attention. Though this model has been supported in patient samples, it
      has not been examined in a healthy adult cohort. Using Principal Components
      Analysis, we examined the explanatory power of this model in 342 adults screened
      for significant medical and psychiatric history. The four derived components
      accounted for 58.7% of the total variance. Results were generally supportive of
      Cohen's [Cohen, R. (1993). The Neuropsychology of Attention. New York: Plenum
      Publishing] model, though further clarification of the relationship between
      processing speed and more complex aspects of attention (e.g. working memory, set
      shifting) is needed. These findings support the notion that attention is not a
      unitary process, but instead comprised of distinct components. Future studies
      including both neuropsychological testing and functional neuroimaging may provide
      important insight into the underpinnings of attentional processes.

PMID- 16887325
TI  - Expectations and associations that heal: Immunomodulatory placebo effects and its
      neurobiology.
AB  - The use of placebo may have accompanied healing and medical practices since their
      origins (Plato; Charmides, 155-156). Recent experimental data indicate that we
      would be well advised to further consider placebo effects in future therapeutic
      strategies, with a better knowledge of their potency, psychological basis and
      underlying neurobiological mechanisms. Current research in the areas of pain,
      depression and Parkinson's disease has uncovered some of the potential
      neurobiological mechanisms of placebo effects. These data indicate that conscious
      expectation and unconscious behavioral conditioning processes appear to be the
      major neurobiological mechanisms capable of releasing endogenous
      neurotransmitters and/or neurohormones that mimic the expected or conditioned
      pharmacological effects. To date, research on placebo responses affecting immune
      related diseases is scarce, but there are consistent indications that skin and
      mucosal inflammatory diseases, in particular, are strongly modulated by placebo
      treatments. However, the brain's capability to modulate peripheral immune
      reactivity has been impressively demonstrated by paradigms of behavioral
      conditioning in animal experiments and human studies. Thus, placebo effects can
      benefit end organ functioning and the overall health of the individual through
      positive expectations and behavioral conditioning processes.

PMID- 16887326
TI  - PECS and VOCAs to enable students with developmental disabilities to make
      requests: an overview of the literature.
AB  - This paper provides an overview of the literature dealing with the use of the
      Picture Exchange Communication System (PECS) and voice output communication aids
      (VOCAs) for promoting the performance of requests by students with developmental
      disabilities. Computerized and manual searches were carried out to identify the
      studies published during the last 15 years (i.e., the period between 1992 and
      2006 during which PECS and VOCA approaches became popular). Thirty-seven studies
      were identified and then divided into three groups concerning the use of the PECS
      or equivalents, the use of VOCAs or equivalents, and the comparison of both these
      approaches, respectively. Of the 173 students involved in studies using the PECS
      or equivalents only three could be considered failures, while a fourth one did
      not progress in the program due to illness. Similarly, of the 39 students who
      used VOCAs or equivalents only three could be considered failures, while one was
      partly successful. Finally, of the 11 students involved in the comparisons
      between PECS and VOCAs none could be classified as a failure. The results are
      very encouraging but methodological concerns and the relatively limited use of
      the systems in terms of request items and request opportunities suggest caution.
      Caution may also be needed in interpreting the reported similarities between the
      two systems in usability and effectiveness.

PMID- 16887327
TI  - The effects of a third generation combined oral contraceptive pill on the
      classical singing voice.
AB  - The success of professional operatic singers depends upon the quality of their
      vocal mechanism. This is known to be sensitive to changes in the endocrine
      environment. Despite a widespread belief among singers that vocal quality changes
      according to the stage of the menstrual cycle, this has received little
      attention. In particular, the possibility that use of the contraceptive pill
      might stabilize vocal quality by "dampening" hormonal fluctuations has not
      previously been studied systematically. Here, we show that drospirenone
      containing oral contraceptive pill (Yasmin, Schering AG, West Sussex, UK) with
      antiandrogenic and antimineralocorticoid properties demonstrates a significant
      reduction in the irregularity of the pattern of vibration of the vocal folds
      during the performance of highly trained classical singers. This study
      constitutes the first double blind, randomized placebo controlled trial to assess
      the effects of the contraceptive pill on the patterns of vibration of the vocal
      folds during the performance of Western classical singing repertoire.

PMID- 16887328
TI  - Correlation of the Voice Handicap Index (VHI) and the Voice-Related Quality of
      Life Measure (V-RQOL).
AB  - The purpose of this study was to investigate the correlation between the Voice
      Handicap Index (VHI) and the Voice-Related Quality of Life Measure (V-RQOL), and
      to test conversion of scores between the two instruments. Understanding the
      relationship between instruments will facilitate comparison of voice outcome
      studies using different measures. A retrospective medical chart review of 140
      consecutive patients with a chief complaint related to their voice presenting for
      speech pathology voice evaluation following laryngology evaluation and diagnosis
      was adopted. Each patient who filled out the VHI and V-RQOL within a 2-week
      period with no intervening treatment was included in the study. Correlation
      analysis for total scores was performed for the patients meeting inclusion
      criteria (n=132). Correlations were also performed as a function of diagnosis.
      Calculated VHI score based on measured V-RQOL score was compared to measured VHI
      score. Pearson correlation between scores on the VHI and V-RQOL was -0.82. There
      was no significant difference between the mean measured and mean calculated VHI
      scores. For individual scores, however, regression analysis did reveal a
      significant difference between calculated and measured VHI. The VHI and V-RQOL
      are highly correlated; however, this study suggests that the two instruments are
      not interchangeable for individuals.

PMID- 16887329
TI  - The voice handicap index: correlation between subjective patient response and
      quantitative assessment of voice.
AB  - The aim of this prospective study is to elucidate the relationship between the
      Voice Handicap Index (VHI) and several voice laboratory measurements in the
      network of the multidimensional voice assessment. Fifty-eight patients were
      included. Each patient replies to the questionnaire and performs a voice
      assessment during the same time. The following parameters were measured: minimum
      frequency, maximum frequency, range, minimum intensity, subglottic pressure, mean
      flow, maximum phonation time, jitter, and dysphonia severity index. Regarding the
      relationship with the scores of the VHI, poor correlations with the minimal
      frequency for all the scores except the emotional one (total and subscales) and
      with the range for only the physical one are found. Seventeen questions correlate
      with the voice laboratory measurements we performed, with a decreased
      distribution between physical, functional, and emotional subscales. We observe
      that acoustic parameter is correlated with the emotional subscale, the parameters
      of the profile range are more often involved in the emotional subscale, as is the
      minimal frequency, but never with the physical subscale, and all the subscales
      are interesting despite the smaller number of differences with the emotional one.
      The VHI and the laboratory measurements give independent informations in
      practice.

PMID- 16887330
TI  - Dynamic switching of neural codes in networks with gap junctions.
AB  - Population rate coding and temporal coding are common neural codes. Recent
      studies suggest that these two codes may be alternatively used in one neural
      system. Based on the fact that there are massive gap junctions in the brain, we
      explore how this switching behavior may be related to neural codes in networks of
      neurons connected by gap junctions. First, we show that under time-varying
      inputs, such neural networks show switching between synchronous and asynchronous
      states. Then, we quantify network dynamics by three mutual information measures
      to show that population rate coding carries more information in asynchronous
      states and temporal coding does so in synchronous states.

PMID- 16887331
TI  - Short-chain fatty acids induce acute phosphorylation of the p38 mitogen-activated
      protein kinase/heat shock protein 27 pathway via GPR43 in the MCF-7 human breast
      cancer cell line.
AB  - The expression of GPR41 and 43, which have recently been identified as G-protein
      coupled cell-surface receptors for short-chain fatty acids (SCFAs), was detected
      in a human breast cancer cell line (MCF-7) by RT-PCR. Acetate, propionate and
      butyrate induced an increase in intracellular Ca2+ in these cells that was not
      blocked by treatment with pertussis toxin (PTX). SCFAs significantly reduced
      forskolin-induced cAMP levels in these cells. The phosphorylation of mitogen
      activated protein kinase (MAPK) p38 was selectively increased by SCFAs. The
      downstream substrate heat shock protein 27 (HSP27) was also phosphorylated by
      SCFAs at Ser-78 and-82, but not-15. Propionate induced elevations in
      intracellular Ca2+ and the phosphorylation of p38 were inhibited by the silencing
      of GPR43 using a specific siRNA. These results suggest that GPR41 and 43 mediate
      SCFA signaling in mammary epithelial cells and thereby play an important role in
      their stress management.

PMID- 16887332
TI  - UNC-51-like kinase regulation of fibroblast growth factor receptor substrate 2/3.
AB  - UNC-51-like kinases (ULK) are members of an evolutionarily conserved sub-family
      of ubiquitously expressed serine/threonine-specific protein kinases. Here we
      report that fibroblast growth factor receptor substrate (FRS) 2/3 are novel ULK2
      carboxy-terminal domain interacting proteins. FRS2/3 are homologs that function
      as adaptor proteins to mediate signaling of multiple receptor tyrosine kinases.
      ULK2 interacts with the phospho-tyrosine binding (PTB) domain of FRS2/3. We
      demonstrate that siRNA targeting ULK2 in mouse P19 cells results in elevated
      FGFR1 mediated FRS3 and SHP2 tyrosyl phosphorylation. In addition, RNAi-mediated
      decrease in ULK2 causes increased interaction between FGFR1 and FRS3. ULK2
      phosphorylates FRS2/3 in vitro, suggesting that ULK2 mediated phosphorylation may
      be a mechanism of FRS2/3 regulation. The data presented support a model in which
      ULK2, by interaction with FRS2/3 and inhibition of SynGAP, functions to
      negatively regulate tyrosyl phosphorylation of signaling proteins downstream of
      FGFR1.

PMID- 16887333
TI  - Molecular genetics of febrile seizures.
AB  - Febrile seizures (FSs) represent the most common form of childhood seizures,
      occurring in 2-5% of infants in Europe and North America and in 6-9% in Japan. It
      has been recognized that there is a significant genetic component for
      susceptibility to this type of seizure. Six susceptibility FS loci have been
      identified on chromosomes 8q13-q21 (FEB1), 19p (FEB2), 2q23-q24 (FEB3), 5q14-q15
      (FEB4), 6q22-q24 (FEB5), and 18p11 (FEB6). Furthermore, mutations in the voltage
      gated sodium channel alpha-1, alpha-2 and beta-1 subunit genes (SCN1A, SCN2A and
      SCN1B) and the GABA(A) receptor gamma-2 subunit gene (GABRG2) have been
      identified in families with a clinical subset of seizures termed "generalized
      epilepsy with febrile seizure plus (GEFS+)". However, the causative genes have
      not been identified in most patients with FSs or GEFS+. Common forms of FSs are
      genetically complex disorders believed to be influenced by variations in several
      susceptibility genes. Recently, several association studies in FSs have been
      reported, but the results vary among different groups and no consistent or
      convincing FS susceptibility genes have emerged. To find a true association,
      larger sample size and newer methodologic refinements are recommended.

PMID- 16887334
TI  - Olanzapine and haloperidol in first episode psychosis: two-year data.
AB  - Few studies have assessed the comparative efficacy and safety of atypical and
      typical antipsychotic medications in patients within their first episode of
      psychosis. This study examined the effectiveness of the atypical antipsychotic
      olanzapine and the typical antipsychotic haloperidol in patients experiencing
      their first episode of a schizophrenia-related psychotic disorder over a 2-year
      treatment period. Two hundred and sixty-three patients were randomized to
      olanzapine or haloperidol in a doubleblind, multisite, international 2-year
      study. Clinical symptoms and side effects were assessed at baseline and
      longitudinally following randomization for the duration of the study. Olanzapine
      and haloperidol treatment were both associated with substantial and comparable
      reductions in symptom severity (the primary outcome measure) over the course of
      the study. However, the treatment groups differed on two secondary efficacy
      measures. Patients were less likely to discontinue treatment with olanzapine than
      with haloperidol: mean time (in days) in the study was significantly greater for
      those treated with olanzapine compared to haloperidol (322.09 vs. 230.38,
      p<0.0085). Moreover, remission rates were greater in patients treated with
      olanzapine as compared to those treated with haloperidol (57.25% vs. 43.94%,
      p<0.036). While extrapyramidal side effects were greater in those treated with
      haloperidol, weight gain, cholesterol level and liver function values were
      greater in patients treated with olanzapine. The data from this study suggest
      some clinical benefits for olanzapine as compared to haloperidol in first episode
      patients, which must be weighed against those adverse effects that are more
      likely with olanzapine.

PMID- 16887336
TI  - Weight gain in first-episode psychosis over three years.

PMID- 16887335
TI  - Project among African-Americans to explore risks for schizophrenia (PAARTNERS):
      recruitment and assessment methods.
AB  - The Project among African-Americans to Explore Risks for Schizophrenia
      (PAARTNERS) is a multi-site, NIMH-funded study that seeks to identify genetic
      polymorphisms that confer susceptibility to schizophrenia among African-Americans
      by linkage mapping and targeted association analyses. Because deficits in certain
      dimensions of cognitive ability are thought to underlie liability to
      schizophrenia, the project also examines cognitive abilities in individuals
      affected by schizophrenia and their extended family members. This article
      describes PAARTNERS study design, ascertainment methods and preliminary sample
      characteristics. We aim to recruit a sample of 1260 African-American families,
      all of whom have at least one proband with schizophrenia or schizoaffective
      disorder. The data collection protocol includes a structured Diagnostic Interview
      for Genetic Studies, Family Interview for Genetic Studies, focused neurocognitive
      assessment, medical records review, and the collection of blood or buccal cells
      for genetic analyses. We have currently completed study procedures for 106
      affected sib-pair, 457 case-parent trio and 23 multiplex families. A total of 289
      probands have completed the best estimate final diagnosis process and 1153
      probands and family members have been administered the computerized
      neuropsychological battery. This project lays the foundation for future analysis
      of cognitive and behavioral endophenotypes. This novel integration of diagnostic,
      neurocognitive and genetic data will also generate valuable information for
      future phenotypic and genetic studies of schizophrenia.

PMID- 16887324
TI  - Analysis of ESTs from Lutzomyia longipalpis sand flies and their contribution
      toward understanding the insect-parasite relationship.
AB  - An expressed sequence tag library has been generated from a sand fly vector of
      visceral leishmaniasis, Lutzomyia longipalpis. A normalized cDNA library was
      constructed from whole adults and 16,608 clones were sequenced from both ends and
      assembled into 10,203 contigs and singlets. Of these 58% showed significant
      similarity to known genes from other organisms, <4% were identical to described
      sand fly genes, and 42% had no match to any database sequence. Our analyses
      revealed putative proteins involved in the barrier function of the gut
      (peritrophins, microvillar proteins, glutamine synthase), digestive physiology
      (secreted and membrane-anchored hydrolytic enzymes), and the immune response
      (gram-negative binding proteins, thioester proteins, scavenger receptors,
      galectins, signaling pathway factors, caspases, serpins, and peroxidases).
      Sequence analysis of this transcriptome dataset has provided new insights into
      genes that might be associated with the response of the vector to the development
      of Leishmania.

PMID- 16887337
TI  - HAN11 binds mDia1 and controls GLI1 transcriptional activity.
AB  - BACKGROUND: The Hedgehog pathway is important in normal and diseased skin. One of
      the key transcription factors in the pathway is GLI1. GLI1-dependent
      transcription is positively regulated by DYRK1A, which is reported to bind HAN11.
      HAN11 is the human homologue of AN11, which controls flavonoid synthesis in
      plants. OBJECTIVE: We wanted to identify other binding partners of HAN11 and
      investigate whether HAN11 regulates GLI1-dependent transcription. METHODS: We
      used TAP-tag purification and GST pull down to identify protein-protein
      interactions and performed luciferase assays of transcriptional activity. We used
      immunofluorescence microscopy to examine the subcellular distribution of HAN11,
      mDia1 and GLI1. We performed in situ hybridisation to compare expression of HAN11
      with GLI1 and patched in mouse embryos. RESULTS: We identified the cytoskeletal
      regulator mDia1 as a binding partner of HAN11. We showed that HAN11 binds the FH2
      actin binding domain of mDia1 and confirmed that HAN11 also interacts with
      DYRK1A. Overexpression of mDia1 or active RhoA caused translocation of HAN11 from
      nucleus to cytoplasm. HAN11 and mDia1 repressed DYRK1A-dependent GLI1
      transcriptional activity. HAN11 overexpression decreased SZ95 sebocyte
      proliferation and increased cytoplasmic GLI1. AN11 was highly expressed in E10.5
      mouse embryo limb buds, in an overlapping pattern with Ptc and GLI1. CONCLUSION:
      These results suggest that AN11 may be a physiological regulator of GLI1
      transcriptional activity.

PMID- 16887338
TI  - Skin barrier function, epidermal proliferation and differentiation in eczema.
AB  - Skin permeability barrier function is impaired in eczema, particularly in contact
      and atopic dermatitis (AD). In contact dermatitis disruption of the barrier by
      irritants and allergens is the primary event, followed by sensitization,
      inflammation, increased epidermal proliferation and changes in differentiation.
      Genetically impaired skin barrier function is already present in non-lesional and
      more pronounced in lesional skin in AD. Increased epidermal proliferation and
      disturbed differentiation, including changes in lipid composition, cause impaired
      barrier function in AD. Defective permeability barrier function enables the
      enhanced penetration of environmental allergens into the skin and initiates
      immunological reactions and inflammation. Barrier dysfunction is therefore
      crucially involved in the pathogenesis of AD. The atopic syndrome represents a
      genetically impaired skin barrier function as well as impaired nasal, bronchial,
      and intestinal mucous membranes leading to AD, allergic rhinitis, bronchial
      asthma or aggravation of AD. Common treatment strategies for eczema include the
      application of lipid-based creams and ointments, which aim toward the restoration
      of the defective permeability barrier, thus helping to normalize proliferation
      and differentiation.

PMID- 16887339
TI  - Effects of nutritional and environmental conditions on Sinorhizobium meliloti
      biofilm formation.
AB  - Rhizobia are non-spore-forming soil bacteria that fix atmospheric nitrogen into
      ammonia in a symbiosis with legume roots. However, in the absence of a legume
      host, rhizobia manage to survive and hence must have evolved strategies to adapt
      to diverse environmental conditions. The capacity to respond to variations in
      nutrient availability enables the persistence of rhizobial species in soil, and
      consequently improves their ability to colonize and to survive in the host plant.
      Rhizobia, like many other soil bacteria, persist in nature most likely in sessile
      communities known as biofilms, which are most often composed of multiple
      microbial species. We have been employing in vitro assays to study environmental
      parameters that might influence biofilm formation in the Medicago symbiont
      Sinorhizobium meliloti. These parameters include carbon source, amount of
      nitrate, phosphate, calcium and magnesium as well as the effects of osmolarity
      and pH. The microtiter plate assay facilitates the detection of subtle
      differences in rhizobial biofilms in response to these parameters, thereby
      providing insight into how environmental stress or nutritional status influences
      rhizobial survival. Nutrients such as sucrose, phosphate and calcium enhance
      biofilm formation as their concentrations increase, whereas extreme temperatures
      and pH negatively affect biofilm formation.

PMID- 16887340
TI  - Potency of DX-619, a novel des-F(6)-quinolone, in haematogenous murine
      bronchopneumonia caused by methicillin-resistant and vancomycin-intermediate
      Staphylococcus aureus.
AB  - In this study, the potency of DX-619, a novel des-fluoro(6)-quinolone agent, was
      compared with that of vancomycin (VCM) in a murine model of haematogenous
      bronchopneumonia infection caused by methicillin-resistant Staphylococcus aureus
      (MRSA) and vancomycin-intermediate S. aureus (VISA). The minimum inhibitory
      concentrations (MICs) of DX-619 and VCM against MRSA were 0.03 microg/mL and 1.0
      microg/mL, respectively, whilst the MICs against VISA were 0.125 microg/mL and
      8.0 microg/mL, respectively. Treatment with DX-619 resulted in a significant
      decrease in the number of viable bacteria in the MRSA infection model (mean+/
      standard error of the mean for control, VCM and DX-619 groups: 7.97+/-0.32,
      7.19+/-0.33 and 2.91+/-0.60 log(10) colony-forming units/lung, respectively). For
      infection with VISA, mice were pre-treated with cyclophosphamide. The survival
      rate of mice treated with DX-619 (90% survival) was significantly higher than
      survival rates in the other two groups (45% both for VCM and control groups;
      P<0.05). Histopathological examination revealed that inflammatory changes in the
      DX-619-treated group were less marked than in the other two groups. The
      parameters in lung tissue for the area under the concentration-time curve/MIC
      ratio both for MRSA and VISA were higher in the DX-619 group than in the VCM
      group. Our results emphasise the potency of DX-619 against MRSA and VISA murine
      haematogenous pulmonary infection.

PMID- 16887341
TI  - Current treatment of adult Duchenne muscular dystrophy.
AB  - Patients with Duchenne muscular dystrophy (DMD) are living longer into adulthood
      due to a variety of improvements in health care practices. This growing patient
      population presents new therapeutic challenges. In this article, we review the
      literature on current treatment of adult DMD as well as our own experience as a
      multidisciplinary team actively caring for 23 men ages 19-38 years of age.
      Approximately one quarter of our adult DMD patients have remained on moderate
      dose corticosteroids. Daily stretching exercises are recommended, particularly of
      the distal upper extremities. Cardiomyopathy is anticipated, detected, and
      treated early with afterload reduction. Oxygen saturation monitoring, noninvasive
      positive pressure ventilation and cough assist devices are routinely used. Other
      medical issues such as osteoporosis, gastrointestinal and urinary symptoms are
      addressed. Current and future therapies directed at prolonging the lifespan of
      those with DMD will result in further increases in this adult population with
      special needs and concerns. These needs are best addressed in a multidisciplinary
      clinic.

PMID- 16887342
TI  - Parcellating the temporal lobes from magnetic resonance images using generic
      software in subjects at high risk of developing schizophrenia.
AB  - A number of reliable techniques have been described that can parcellate temporal
      neo-cortex from MRI images to preserve topographical characteristics of
      individual brains, but these tend to use in-house software. We describe here an
      adaptation of the methods previously described by Kim et al. [Kim, J.J., Crespo
      Facorro, B., Andreasen, N.C., O'Leary, D.S., Zhang, B., Harris, G., Magnotta,
      V.A., 2000. An MRI-based parcellation method for the temporal lobe. Neuroimage
      11, 271-288], but utilising commercially and, therefore, generally available
      software. Using Analyze, we traced individual sulci and identified coronal
      bounding planes, and used a combination of three orthogonal plane views, manual
      limit tracing and semi-automated edge detection to parcellate 13 sub-regions of
      temporal neo-cortex from sets of serial coronal slices. We applied this technique
      to the baseline scans of the first seven subjects in the Edinburgh High Risk
      Study (EHRS) who developed schizophrenia, and a matched group of healthy
      controls, to see if temporal lobe sub-regional volumes could predict the onset of
      schizophrenia. Two relatively inexperienced raters developed these techniques in
      a short time period, and intra-rater intra-class correlation coefficients (ICC)
      ranged from 0.56 to 0.99, while the mean inter-rater ICC was 0.90 (range 0.55
      0.99). There were, however, no significant differences in temporal lobe sub
      regional volumes between the two groups we examined. We have, therefore,
      developed a reliable parcellation technique that requires relatively little
      training. It is, however, a laborious process, and it remains uncertain whether
      it is more sensitive to early disease processes in pre-schizophrenia than are
      other image-analysis techniques.

PMID- 16887343
TI  - 3-Methylglutaric acid as a 13C solid-state NMR standard.
AB  - The calibration of a solid-state NMR spectrometer requires setting the magic
      angle, setting the reference and decoupler frequencies, ensuring that the
      magnetic field is homogeneous across the sample volume, optimizing the signal-to
      noise ratio, determining the pi/2 pulse durations, and optimizing the Hartman
      Hahn matching condition. Each task has one or more widely accepted standards,
      such as potassium bromide for setting the magic angle, adamantane for optimizing
      magnet homogeneity, and hexamethylbenzene or glycine for measuring the signal-to
      noise ratio. We show that all of these tasks can be performed using 3
      methylglutaric acid (MGA). In the case of high-powered decoupling, the CH(2) and
      CH carbon peaks of MGA provide an opportunity to evaluate the decoupling in a
      manner that is superior to any of the commonly used standard compounds. Thus, MGA
      can be used as a single solid-state NMR standard compound to perform all
      calibration steps except for magnet shimming.

PMID- 16887344
TI  - Oxygen tolerance of an implantable polymer/enzyme composite glutamate biosensor
      displaying polycation-enhanced substrate sensitivity.
AB  - Biosensors were fabricated at neutral pH by sequentially depositing the
      polycation polyethyleneimine (PEI), the stereoselective enzyme L-glutamate
      oxidase (GluOx) and the permselective barrier poly-ortho-phenylenediamine (PPD)
      onto 125-microm diameter Pt wire electrodes (Pt/PEI/GluOx/PPD). These devices
      were calibrated amperometrically at 0.7 V versus SCE to determine the Michaelis
      Menten parameters for enzyme substrate, l-glutamate (Glu) and co-substrate,
      dioxygen. The presence of PEI produced a 10-fold enhancement in the detection
      limit for Glu (approximately 20 nM) compared with the corresponding PEI-free
      configurations (Pt/GluOx/PPD), without undermining their fast response time
      (approximately 2 s). Most remarkable was the finding that, although some designs
      of PEI-containing biosensors showed a 10-fold increase in linear region
      sensitivity to Glu, their oxygen dependence remained low.

PMID- 16887345
TI  - A rapid competitive binding nonseparation electrochemical enzyme immunoassay
      (NEEIA) test strip for microcystin-LR (MCLR) determination.
AB  - A competitive binding nonseparation electrochemical enzyme immunoassay (NEEIA) is
      described for the determination of microcystin-LR (MCLR) using a double-sided
      microporous gold electrode in cartridge-type cells. A gold film sputtered on one
      side of porous nylon membrane constitutes a working electrode, while another gold
      film formed on the opposite side serves as a pseudo reference electrode. After
      immobilizing MCLR antibody on working electrode by physical adsorption, the
      double-sided electrode was placed simply in a diffusion U-type or within a dry
      strip-type cell with a conjugate pad pre-loaded with a glucose oxidase labeled
      MCLR (GOx-MCLR) on working electrode side. Assays were performed in two steps: an
      MCLR-containing sample mixed with a known amount of GOx-MCLR conjugate either in
      buffer solution or in pre-loaded dry pad was incubated for an appropriate period
      (about 10 min) to induce competitive reaction with an immobilized anti-MCLR
      antibody on working electrode, and a fixed concentration of glucose solution
      (substrate) was then added to the backside of the working electrode. Due to the
      competitive nature of the assay, enzymatically generated product, hydrogen
      peroxide (H2O2), was detected at the working gold electrode (at +800 mV versus
      Au) by oxidation, and the magnitude of amperometric current was inversely
      proportional to the concentration of MCLR in the sample. The response time after
      substrate addition was about 30s. Mean recovery of MCLR added to tap water was
      93.5%, with a coefficient of variation (CV) of 6.6%. The proposed competitive
      NEEIA system is in general comparable to existing heterogeneous enzyme
      immunoassays with a similar detection limit (100 pg/mL MCLR), and suitable for
      developing a disposable type biosensor for on-site monitoring of environment.

PMID- 16887346
TI  - Hemoglobin niobate composite based biosensor for efficient determination of
      hydrogen peroxide in a broad pH range.
AB  - Inorganic layered niobates (HCa2Nb3O10) were used as immobilization matrices of
      hemoglobin (Hb) because of their tunable interlayer spaces, large surface areas
      and good biocompatibilities. A pair of well-defined, quasi-reversible cycle
      voltammertric peaks were obtained at the Hb-HCa2Nb3O10 modified pyrolytic
      graphite electrode, suggesting that the layered niobates facilitate the electron
      transfer between the proteins and the electrode. Hb-HCa2Nb3O10 modified electrode
      exhibited electrocatalytic response for monitoring H2O2 with a large linear
      detection range from 25 microM to 3.0 mM and a relatively high sensitivity of 172
      microA mM-1 cm-2. Based on the stabilizing effect of the layered niobates, Hb
      HCa2Nb3O10 modified electrode can detect H2O2 in strongly acidic and basic
      solutions with pH of 1-12, which greatly expands the application fields of
      biosensors.

PMID- 16887347
TI  - Novel tricyclic azepine derivatives: Biological evaluation of pyrimido[4,5-b]-1,4
      benzoxazepines, thiazepines, and diazepines as inhibitors of the epidermal growth
      factor receptor tyrosine kinase.
AB  - Novel tricyclic derivatives containing an oxazepine, thiazepine, or diazepine
      ring were studied for their EGFR tyrosine kinase inhibitory activity. While the
      oxazepines were in general more potent than thiazepines, the diazepines displayed
      somewhat different structure-activity relationships. Moreover, the diazepines, in
      contrast to the oxazepines, showed appreciable inhibitory activity against the
      KDR tyrosine kinase. Furthermore, both oxazepines and diazepines demonstrated
      significant ability to inhibit autophosphorylation of EGFR in DiFi cells
      (generally, IC(50) values in the single-digit micromolar to submicromolar range).

PMID- 16887348
TI  - Solid-phase synthesis and structure-activity relationships of novel biarylethers
      as melanin-concentrating hormone receptor-1 antagonists.
AB  - Melanin-concentrating hormone (MCH) is a cyclic 19 amino acid orexigenic
      neuropeptide. The action of MCH on feeding is thought to involve the activation
      of its respective G protein-coupled receptor MCH-R1. Consequently, antagonists
      that block MCH regulated MCH-R1 activity may provide a viable approach to the
      treatment of diet-induced obesity. This communication reports the discovery of a
      novel MCH-R1 receptor antagonist, the biarylether 7, identified through high
      throughput screening. The solid-phase synthesis and structure-activity
      relationship of related analogs is described.

PMID- 16887349
TI  - Current use of antibiotic prophylaxis in breast surgery: a nationwide survey.
AB  - There is currently no consensus regarding the use of antibiotic prophylaxis in
      breast surgery. This postal survey aimed to establish the current practice in
      perioperative antibiotic use for breast surgery in the United Kingdom.
      Questionnaires were sent to 406 breast surgeons, enquiring about antibiotic use
      for common breast procedures. A total of 266 completed questionnaires were
      returned (65.5%). Over 80% of surgeons who performed breast augmentations,
      myocutaneous flap reconstructions and implant reconstructions used antibiotic
      prophylaxis. Up to 33% used antibiotic prophylaxis for wide local excisions
      (WLEs), mastectomies and axillary surgery for breast cancer, while 62% and 45%
      used antibiotics for breast reductions and duct excisions, respectively. The most
      common antibiotic used was co-amoxiclav. The variation in practice regarding
      antibiotic prophylaxis in breast surgery reflects the lack of reliable evidence
      for its efficacy. Further randomised controlled trials are required, taking into
      consideration specific risk factors affecting postoperative infection rate for
      breast surgery.

PMID- 16887351
TI  - Averaged EMG profiles in jogging and running at different speeds.
AB  - EMGs were collected from 14 muscles with surface electrodes in 10 subjects
      walking 1.25-2.25 ms(-1) and running 1.25-4.5 ms(-1). The EMGs were rectified,
      interpolated in 100% of the stride, and averaged over all subjects to give an
      average profile. In running, these profiles could be decomposed into 10 basic
      patterns, 8 of which represented only a single burst. Muscles could be divided
      into a quadriceps, hamstrings, calf and gluteal group, the profiles of which were
      composed of the same basic patterns. The amplitude of some bursts was constant,
      but other ones varied with running speed. This speed dependency was generally
      different between muscles of the same group. Many muscles show a similar profile
      in running as in walking. The most notable exception is the calf group, which
      shows activation in early stance (86-125%), together with quadriceps, instead of
      in late stance (26-55%) as in walking. This is also visible in low-speed running,
      'jogging', where stance extends to 46% or 57%, instead of 30-37% as in normal
      running. Jogging shows some additional differences with normal running, related
      to this prolonged stance phase.

PMID- 16887350
TI  - IKK epsilon regulates F actin assembly and interacts with Drosophila IAP1 in
      cellular morphogenesis.
AB  - Differentiated cells assume complex shapes through polarized cell migration and
      growth. These processes require the restricted organization of the actin
      cytoskeleton at limited subcellular regions. IKK epsilon is a member of the
      IkappaB kinase family, and its developmental role has not been clear. Drosophila
      IKK epsilon was localized to the ruffling membrane of cultured cells and was
      required for F actin turnover at the cell margin. In IKK epsilon mutants,
      tracheal terminal cells, bristles, and arista laterals, which require accurate F
      actin assembly for their polarized elongation, all exhibited aberrantly branched
      morphology. These phenotypes were sensitive to a change in the dosage of
      Drosophila inhibitor of apoptosis protein 1 (DIAP1) and the caspase DRONC without
      apparent change in cell viability. In contrast to this, hyperactivation of IKK
      epsilon destabilized F actin-based structures. Expression of a dominant-negative
      form of IKK epsilon increased the amount of DIAP1. The results suggest that at
      the physiological level, IKK epsilon acts as a negative regulator of F actin
      assembly and maintains the fidelity of polarized elongation during cell
      morphogenesis. This IKK epsilon function involves the negative regulation of the
      nonapoptotic activity of DIAP1.

PMID- 16887352
TI  - The effect of a single treatment of the Protonics system on lower extremity
      kinematics during gait and the lateral step up exercise.
AB  - INTRODUCTION: Patellofemoral pain (PFP) is often attributed to abnormal patellar
      tracking. The Protonics knee orthosis was developed to reduce femoral internal
      rotation by altering pelvic alignment via hamstring activation. The purpose of
      this research was to determine if a single treatment with the orthosis improved
      lower extremity alignment during gait and the lateral step up exercise. We
      hypothesized that anterior pelvic tilt, hip internal rotation and adduction, and
      external rotation of the tibia with respect to the femur would decrease after use
      of the brace. METHODS: Nineteen females (23.4+/-3.1 year, 1.66+/-0.05 m, 65.3+/
      20.4 kg) with chronic PFP participated. Three-dimensional kinematic data were
      collected for each subject at 60 Hz during pre-treatment (PRE), after a placebo
      condition with the orthosis set at zero resistance (PLAC), and post-treatment
      (POST). Treatment consisted of having the subject perform the rehabilitation
      exercises recommended by the Protonics manufacturer. A repeated measures ANOVA
      was performed on each dependent variable (alpha=0.05). RESULTS: This
      investigation did not verify the changes in alignment proposed by the
      manufacturer as a result of acute application of the Protonics system. However,
      after the use of the brace, pelvic rotation and hip hike were decreased during
      the lateral step up exercise. CONCLUSION: Based on the results of this study, it
      was concluded that a single application of the Protonics system did not alter
      anterior pelvic tilt, hip internal rotation and adduction, or tibial external
      rotation during the lateral step up and gait.

PMID- 16887353
TI  - Novel 1,3-dicarbonyl compounds having 2(3H)-benzazolonic heterocycles as
      PPARgamma agonists.
AB  - A series of 1,3-dicarbonyl compounds having 2(3H)-benzazolonic heterocycles has
      been synthesized and tested for PPARgamma agonist activity. SAR were developed
      and revealed that 6-acyl-2(3H)-benzothiazolone derivatives with 1,3-dicarbonyl
      group were the most potent. IP administration of compound 22 exhibited comparable
      levels of glucose and triglyceride correction to PO administration of
      rosiglitazone in the ob/ob mouse studies.

PMID- 16887354
TI  - Synthesis and antiproliferative evaluation of certain pyrido[3,2-g]quinoline
      derivatives.
AB  - The present report describes the synthesis and evaluation of tricyclic pyrido[3,2
      g]quinoline derivatives in which an additional pyridine ring is linearly fused on
      the antibacterial quinoline-3-carboxylic acid. Among them, only diethyl 4,6
      diamino-10-methylpyrido[3,2-g]quinoline-3,7-dicarboxylate (9a) and diethyl 4,6
      bis-(3-dimethylaminopropylamino)-10-methylpyrido[3,2-g]quinoline-3,7
      dicarboxylate (9d) were able to completely inhibit cell proliferation of MCF7
      (Breast), NCI-H460 (Lung), and SF-268 (CNS) implying either amino or
      dimethylaminopropyl moiety at C-4 and C-6 positions is crucial for the
      antiproliferative activity of pyrido[3,2-g]quinoline derivatives. Compounds 9a-9d
      were further evaluated for their activity against the growth of MCF-7 and two
      prostate cancer cell lines, LNCaP and PC-3. Results indicated the
      antiproliferative activity decreased in an order 9d>9a>>9b and 9c. Compound 9d
      was the most cytotoxic with an IC50 value of 5.63 and 3.96 microM, respectively,
      against LNCaP and MCF-7. Flow cytometric analyses revealed that growth inhibition
      of LNCaP by 9d was due to cell cycle arrest in G1 phase, and followed by
      apoptosis.

PMID- 16887355
TI  - Structure-activity relationships in nitrothiophenes.
AB  - The structure and electronic properties of a series of biologically active 2
      nitrothiophenes (1) have been calculated using both semi-empirical and ab initio
      molecular orbital methods. Multi-linear regression analysis suggests that there
      is a reasonable correlation between the experimental activity of the derivatives
      against either Escherichia coli or Micrococcus luteus and calculated properties
      such as the HOMO energies, the total atomic charges and ring angles at the
      heterocyclic sulfur atom, but there is no correlation with the calculated
      solvation energies or dipole moments. The presence or absence of an additional
      nitro group at the 3-position of the ring also has a significant effect on the
      activity. From the derived QSAR equations, the 2-chloro- or 2-bromo-3,5
      dinitrothiophenes (1a and 1c) are predicted to show the highest activity against
      both bacteria, while 2-nitrothiophene (1n) is predicted to be the least active,
      in line with the experimental results.

PMID- 16887356
TI  - Experimental investigation and nuclear model calculations on proton-induced
      reactions on highly enriched 114Cd at low energies.
AB  - The excitation functions of both Cd(p,n)(114m)In114 and Cd(p,2n)(113m)In114
      reactions were evaluated experimentally by the stacked-foil technique on highly
      enriched (114)Cd isotope. Two stacks were irradiated by proton beam with energies
      14.7 and 18MeV on the MGC-20 cyclotron at Nuclear Research Center, AEA, Egypt.
      The present results support the previous measurements. The theoretical
      interpretations of the measured excitation functions were done by EMPIRE-II
      (v2.18 Mondovi) code. Compatibility with predictions of hybrid Monte Carlo
      simulation (HMS) pre-equilibrium mechanism was obtained.

PMID- 16887358
TI  - Early-life fluoxetine exposure reduced functional deficits after hypoxic-ischemia
      brain injury in rat pups.
AB  - Neuroplasticity after perinatal programming may allow for neuroprotection against
      hypoxic-ischemia (HI) at birth. The cAMP response element-binding protein (CREB)
      is a key mediator of stimulus-induced nuclear responses that underlie survival,
      memory and plasticity of nervous system. Chronic treatment of fluoxetine, a
      selective serotonin reuptake inhibitor, can upregulate CREB activation in the
      hippocampus. We examined whether fluoxetine administration before HI may protect
      against neonatal HI brain injury through CREB-mediated mechanisms. We found that
      low-dose fluoxetine pretreatment in a neonatal HI brain injury model
      significantly reduced functional deficits at adulthood. The neuroprotective
      mechanisms were associated with increased CREB phosphorylation and increased
      brain-derived neurotrophic factor and synapsin I mRNA expression in the
      hippocampus. Neurogenesis also increased because of greater precursor cell
      survival in the hippocampal dentate gyrus. These findings suggest that functional
      deficits after HI in the developing brain can be reduced by agents that enhance
      neural plasticity and neurogenesis through CREB activation.

PMID- 16887357
TI  - Activated microglia stimulate transcriptional changes in primary oligodendrocytes
      via IL-1beta.
AB  - No therapy currently exists to repair demyelinated lesions in multiple sclerosis.
      However, the use of IgM antibodies may provide a valuable therapeutic avenue for
      evoking such repair. Unfortunately, the mechanism of immunoglobulin action in CNS
      repair is currently unknown but may depend upon complex interactions between
      multiple cell types rather than upon direct activation of a single cell type.
      Using rat mixed glial cultures containing oligodendrocytes, microglia, and
      astrocytes, we found that the Fc portion of human IgM shifts microglia to an
      activated phenotype, reduces glial proliferation, upregulates a variety of
      immediate early genes, including JunB, Egr-1, and c-Fos, and stimulates
      microglial production and release of IL-1beta. Microglia-derived IL-1beta
      consequently triggers transcriptional upregulation of immediate early genes such
      as c-Jun, Egr-1, and c-Fos in the mixed glial cultures, and stimulates the
      upregulation of late response genes such as lipocalin in purified
      oligodendrocytes. Treatment with an IL-1beta receptor antagonist abrogates the
      effects of Fcmu on glial proliferation and prevents the upregulation of lipocalin
      in response to Fcmu, but does not prevent Fcmu-mediated upregulation of IL-1beta,
      suggesting that IL-1beta mediates at least some of the downstream effects of Fcmu
      in mixed glial cultures. We hypothesize that Fcmu-stimulated IL-1beta-induced
      upregulation of immediate early and late response genes in oligodendrocytes may
      promote CNS repair.

PMID- 16887360
TI  - Assessment of coronary artery bypass grafts patency with different magnetic
      resonance technologies.
AB  - OBJECTIVE: The aim of the study was to evaluate the diagnostic accuracy of
      different magnetic resonance (MR) sequences in the assessment of coronary artery
      bypass graft patency and the evaluation of distal anastomoses with a spin echo
      sequence (Haste). PATIENTS AND METHODS: Twenty-five patients were examined with
      all the three techniques and 185 patients with 481 distal anastomoses were
      examined with the Haste sequence at a 1.5 TMR scanner and coronary angiography. A
      two-dimensional T(2)-weigthed breath-hold half-Fourier acquisition single-shot
      turbo spin echo sequence (Haste), a Navigator sequence and a gadolinium-enhanced
      Fisp-3-D sequence were performed. All images were evaluated independently by a
      radiologist and cardiologist and compared to the conventional coronary
      angiography. The observers were blinded to the coronary angiography findings, but
      informed in regard to the surgical graft anastomosis. RESULTS: With the Haste
      sequence 80% of the distal anastomoses were recognized. The sensitivity and
      specificity for the evaluation of the distal anastomosis with the Haste sequence
      was 94% and 75%. The Navigator and the Fisp-3-D sequences showed a sensitivity of
      74% and 94% and a specificity of 78% and 88%. CONCLUSION: The best results were
      achieved with the Haste sequence, a reliable assessment of graft patency of the
      distal anastomosis is possible. The best imaging of proximal IMA segments was
      possible with the Fisp-3-D sequence. Due to the low sensitivity and specificity,
      the use of the Navigator sequence was stopped in our center. Further improvements
      of the spatial resolution and the image quality are necessary to recommend this
      MR techniques for routine clinical use.

PMID- 16887359
TI  - Characterization of alpha1-antitrypsin as a heme oxygenase-1 suppressor in
      Alzheimer plasma.
AB  - Heme oxygenase-1 (HO-1) mRNA and protein levels are diminished in Alzheimer
      disease (AD) blood, cerebrospinal fluid (CSF) and choroid plexus. Herein, the
      presence of a heme oxygenase-1 suppressor (HOS) factor was ascertained by
      astroglial bioassay, biochemical techniques and immunofluorescence confocal
      microscopy. We report significantly augmented plasma HOS activity in AD patients
      relative to healthy elderly and neurological controls. The HOS factor was
      determined to be a 50-100 kDa heat-labile, heparin-binding glycoprotein that is
      unrelated to antioxidant ingestion, plasma total antioxidant capacity,
      circulating cortisol levels or apolipoprotein E epsilon4 carrier status. HOS
      bioactivity was recapitulated by exogenous alpha(1)-antitrypsin. alpha(1)
      antitrypsin levels were significantly increased in AD plasma and correlated with
      HOS activity and MMSE scores. alpha(1)-antitrypsin immunodepletion attenuated HOS
      activity of AD plasma. In AD brain, alpha(1)-antitrypsin immunoreactivity was
      augmented and co-distributed with HO-1. HOS activity of alpha(1)-antitrypsin may
      curtail HO-1-dependent derangement of cerebral iron homeostasis and account for
      diminished HO-1 expression in AD peripheral tissues.

PMID- 16887361
TI  - Video-assisted thoracic surgery utilizing local anesthesia and sedation.
AB  - OBJECTIVE: Video-assisted thoracic surgery (VATS) is usually performed with
      general anesthesia and double-lumen endotracheal intubation, but minor procedures
      have been carried out with patients spontaneously breathing and with epidural or
      regional analgesia. We have broadened our indications for VATS utilizing purely
      local anesthesia and sedation. METHODS: The medical records of all patients
      undergoing VATS under local anesthesia and sedation at Geisinger Wyoming Valley
      Medical Center between 7/1/02 and 6/1/06 were reviewed. All procedures were
      performed in the operating room with patients in full lateral position; no
      patient had endotracheal intubation or epidural or nerve block analgesia.
      RESULTS: One hundred and fifteen patients, ranging in age from 21 to 88 years and
      in size from 40 to 172 kg, underwent 126 video-assisted thoracic operations:
      pleural biopsy/effusion drainage with or without talc 81, drainage of empyema 21,
      lung biopsy 18, evacuate hemothorax 3, pericardial window 2, biopsy chest wall
      mass 1. No patient required intubation or conversion to thoracotomy. Three
      patients who underwent lung biopsy died of their underlying disease
      (cytomegalovirus and pneumocystis, primary amyloidosis, metastatic cancer to
      contra-lateral lung) on postoperative days 18, 14, and 4, respectively. One
      patient developed transient renal insufficiency attributed to ketorolac.
      CONCLUSION: VATS utilizing local anesthesia and sedation is well tolerated, safe,
      and valuable for an increasing number of indications.

PMID- 16887362
TI  - Inverse correlation between serum free IGF-I and IGFBP-3 levels and blood
      pressure in patients affected with type 1 diabetes.
AB  - BACKGROUND: Even though the gene encoding for IGF-I is considered of most
      importance amongst blood pressure-regulating genes in mouse models, little and
      discordant data are available in literature for what concerns a possible
      relationship between blood pressure and serum free IGF-I values in humans. In
      addition, no information is available on type 1 diabetes patients. AIM: Our aim
      is to analyze the relationship between systolic and diastolic blood pressure and
      serum free IGF-I and IGFBP-3 levels in subjects suffering from type 1 diabetes.
      RESULTS: A highly significant inverse correlation was observed between serum free
      IGF-I levels and both systolic and diastolic blood pressure in subjects affected
      with type 1 diabetes. Similar but less significant relationships were observed
      for IGFBP-3, whose levels were also significantly and directly correlated with
      those of free IGF-I. The correlation between systolic and diastolic blood
      pressures with free IGF-I and between systolic blood pressure and IGFBP-3 levels
      were confirmed after adjusting for age, gender, age at diagnosis, disease
      duration, familial history, HBA1c, and amount of insulin administered by
      multivariate logistic regression analysis. A decrease in free IGF-I and IGFBP-3
      levels, along with increases in blood pressure, significantly influenced the
      presence of diabetic complications, confirming how these molecules may be
      considered as severity markers for patients with type 1 diabetes as well as risk
      factors for altered pressure control linked diseases.

PMID- 16887363
TI  - The effect of caffeic acid phenethyl ester (CAPE) on histopathological changes in
      testicular ischemia-reperfusion injury.
AB  - Testicular torsion causes an enhanced formation of reactive oxygen species which
      contributes to the pathophysiology of ischemia-reperfusion injury in the testis.
      We evaluated here the effect of caffeic acid phenethyl ester (CAPE), a new
      antioxidant and anti-inflammatory agent on histopathological changes in
      testicular ischemia-reperfusion injury. Adult male Wistar rats were divided into
      six groups of five each: control group 1 (n=5), sham operation group 2 (n=5),
      torsion/detorsion (T/D) group 3 (n=5), T/D+saline group 4 (n=5), T/D+CAPE group 5
      (n=5) and T/D+CAPE group 6 (n=5). Group 1 served to determine baseline values of
      histopathological parameters, group 2 animals that underwent sham operation
      served as a control, while groups 3-6 animals were subjected to left unilateral
      torsion (2 h) and detorsion (24 h) periods. All the groups were sacrified 24 h
      later except group 6. CAPE was injected 2 days with the same dose to the group 6
      and it was sacrified 48 h later. One testis removed and fixed in Bouin's
      solution. After routine tissue processing myeloperoxidase (MPO) and inducible
      nitric oxide synthase (iNOS) immunohistochemical methods were studied from
      paraffin embedded tissues. Treating rats with CAPE (applied at 10 micromol/kg, 30
      min prior to T/D) attenuated the testicular injury and as well as the tissue
      levels of MPO. At the same time testis tissue showed a decrease in iNOS activity.
      Our results suggest that CAPE treatment have a protective role on testicular T/D
      and this effect may be due to inhibiting the neutrophil mediated cellular injury.

PMID- 16887364
TI  - An analytical strategy for quaternary ammonium neuromuscular blocking agents in a
      forensic setting using LC-MS/MS on a tandem quadrupole/time-of-flight instrument.
AB  - An analytical strategy is described for analyzing quaternary ammonium
      neuromuscular blocking agents in a wide variety of biological specimens in a
      forensic setting. Neuromuscular blocking agents such as succinylcholine,
      pancuronium, and tubocurarine, often used as paralytic agents during surgery, are
      occasionally suspected as paralytic poisoning agents involved in suspected
      homicide and suicide cases. Because suspicion in such cases can develop slowly,
      the age, nature, and quality of available specimens varies greatly. The compounds
      are challenging analytically because of their simultaneous precharged yet
      lipophilic character. An analytical strategy has been devised for extracting
      these compounds from complex matrices using a combination of a modified Bligh and
      Dyer liquid-liquid extraction (used in reverse) followed by reverse-phase ion
      pairing solid-phase extraction using heptafluorobutyric acid as an ion pairing
      reagent. Final analysis is by LC-MS/MS using a tandem quadrupole orthogonal
      acceleration time of flight instrument (Q-TOF) with repetitive product ion
      scanning at high resolution. Native and spiked specimens are compared for both
      quantitative and especially qualitative purposes. The method has been applied to
      a wide variety of fluid and tissue specimen types, including numerous specimens
      from exhumation autopsies. For most specimens, detection limits are in the 2 to
      10 ng/g range. Succinylmonocholine has been demonstrated to be present at low
      levels in normal posthumous kidney and liver. The Q-TOF is an excellent platform
      for forensic analytical investigations. This analytical strategy should also be
      applicable to other problematic analytes and sample matrices.

PMID- 16887365
TI  - Gene targeting methods for studying nuclear transport factors in mice.
AB  - Genetically engineered mice have been widely used to study gene function in a
      variety of life-science disciplines. However, the use of animal models in the
      field of nucleocytoplasmic transport has been limited, mainly because disruption
      of individual transport factors is expected to deregulate basic biological
      processes so severely that the embryo dies at an early stage in development.
      Early studies in which transport factors were knocked out in mice have confirmed
      this notion. Recent work has shown that hypomorphic alleles are very useful for
      studying essential genes at the organismal level. In combination with wild-type
      and knockout alleles, hypomorphic alleles can be used to generate a series of
      mice in which the expression of a protein is gradually reduced from normal to
      zero. Within this series, there is often an allelic combination that yields
      liveborn mice that develop overt phenotypes as they age, and that can be used to
      study the physiological relevance of the protein. In this article, we present an
      efficient method for generating an allelic series of mice. It involves the use of
      a multi-purpose gene-targeting vector that produces a hypomorphic allele that can
      also be converted into conditional and knockout alleles within the mouse. This
      method saves time and provides flexibility in terms of choosing the most
      appropriate model for studying components of the nucleocytoplasmic machinery at
      the organismal level.

PMID- 16887366
TI  - Enhancer detection in the zebrafish using pseudotyped murine retroviruses.
AB  - Vectors based on murine retroviruses are among the most efficient means to insert
      reporter constructs into the context of a vertebrate chromosome with the aim to
      visualize cis-regulatory information available to a basal promoter at the site of
      insertion. In combination with using the zebrafish embryo as a readout for the
      activity of regulatory elements, enhancer detection becomes a powerful technique
      for gene discovery and for the mapping of the extent of regulatory domains in a
      vertebrate genome. Our laboratory has performed the only large-scale enhancer
      detection screen to date in any vertebrate and we describe in this paper the
      methods we developed to generate viral particles, to insert reporter constructs
      into the zebrafish germ line, the screening of detection events in heterozygous
      F1 embryos, and the isolation of genomic sequence flanking the inserted vector
      for the purpose of genomic mapping. Given sufficient scale, the technology
      described here can be used to obtain cis-regulatory information across the entire
      zebrafish genome for any given basal promoter.

PMID- 16887367
TI  - Segmentation of focal cortical dysplasia lesions on MRI using level set
      evolution.
AB  - Focal cortical dysplasia (FCD) is the most frequent malformation of cortical
      development in patients with medically intractable epilepsy. On MRI, FCD lesions
      are not easily differentiable from the normal cortex and defining their spatial
      extent is challenging. In this paper, we introduce a method to segment FCD
      lesions on T1-weighted MRI. It relies on two successive three-dimensional
      deformable models, whose evolutions are based on the level set framework. The
      first deformable model is driven by probability maps obtained from three MRI
      features: cortical thickness, relative intensity and gradient. These features
      correspond to the visual characteristics of FCD and allow discriminating lesions
      and normal tissues. In a second stage, the previous result is expanded towards
      the underlying and overlying cortical boundaries, throughout the whole cortical
      section. The method was quantitatively evaluated by comparison with manually
      traced labels in 18 patients with FCD. The automated segmentations achieved a
      strong agreement with the manuals labels, demonstrating the applicability of the
      method to assist the delineation of FCD lesions on MRI. This new approach may
      become a useful tool for the presurgical evaluation of patients with intractable
      epilepsy related to cortical dysplasia.

PMID- 16887368
TI  - Functional neuroimaging with MEG: normative language profiles.
AB  - The reliability of language-specific brain activation profiles was assessed using
      Magnetoencephalography (MEG) in five experiments involving ninety-seven normal
      volunteers of both genders ranging in age from seven to eighty-four years. MEG
      data were analyzed with a fully automated method to eliminate subjective
      judgments in the process of deriving the activation profiles. Across all
      experiments, profiles were characterized by significant bilateral activity
      centered in the superior temporal gyrus, and in activity lateralized to the left
      middle temporal gyrus. These features were invariant across age, gender,
      variation in task characteristics, and mode of stimulus presentation. The
      absolute amount of activation, however, did decline with age in the auditory
      tasks. Moreover, contrary to the commonly held belief that left hemisphere
      dominance for language is greater in men than in women, our data revealed an
      opposite albeit a not consistently significant trend.

PMID- 16887369
TI  - A randomised trial of endovascular and open surgery for ruptured abdominal aortic
      aneurysm - results of a pilot study and lessons learned for future studies.
AB  - INTRODUCTION: EVAR has the potential to improve outcome after ruptured abdominal
      aortic aneurysm (AAA). Published series have been based upon selected
      populations. METHODS: An interim analysis of a single centre prospective
      randomised controlled trial comparing endovascular aneurysm repair (EVAR) with
      open aneurysm repair (OAR) in patients with ruptured AAA was performed. Patients
      who had a ruptured AAA and who were considered fit for open repair were
      randomised to EVAR or OAR after consent had been obtained. Those in the EVAR
      group had pre-operative spiral computed tomographic angiography (CTA). The
      primary endpoint was operative (30-day) mortality and secondary endpoints were
      moderate or severe operative complications, hospital stay and time between
      diagnosis and operation. A power study calculation required 100 patients to be
      recruited. RESULTS: Between September 2002 and December 2004, 103 patients were
      admitted with suspected ruptured AAA. Only 32 patients were recruited to the
      study. Of these, four patients died before receiving surgical treatment. On an
      intention to treat basis the 30-day mortality rate was 53% in the EVAR group and
      53% in the OAR group. Moderate or severe operative complications occurred in 77%
      in the EVAR group and in 80% in the OAR group. Median total hospital stay in the
      EVAR group was 10 days (inter-quartile range 6-28) and 12 days (4-52) in the OAR
      group. Median time between diagnosis and operation was 75 minutes (64-126) in the
      EVAR group and 100 minutes (48-138) in the OAR group. CONCLUSIONS: Despite the
      relative high operative mortality in the EVAR group, these preliminary results
      show that it is possible to recruit patients to a randomised trial of OAR and
      EVAR in patients with ruptured AAA. CT scanning does not delay treatment.

PMID- 16887370
TI  - Vertebrate reproductive stem cells: recent insights and technological advances.
AB  - How limited is the ability of stem cells to generate gametes or differentiated
      somatic cells? Recent outcomes of research with stem cells from both embryonic
      and adult origin will be discussed with particular attention to results that
      challenge conventional wisdom about the presence of reproductive stem cells in
      adults and the plasticity of adult stem cell types. The ability of embryonic germ
      cells, primordial germ cells, oogonia, gonocytes and spermatogonial stem cells to
      differentiate or dedifferentiate into overlapping cell types is described as well
      as the implications of generating differentiated somatic cells of multiple
      lineages from adult reproductive stem cells.

PMID- 16887371
TI  - Taurine in the anterior cingulate cortex diminishes neuropathic nociception: a
      possible interaction with the glycine(A) receptor.
AB  - Taurine is an inhibitory amino-acid which has been proposed as a nociceptive
      process neuromodulator. The glycine(A) receptor (glyR(A)) has been postulated as
      a receptor in which taurine exerts its function. Functional image studies have
      documented the role of the anterior cingulate cortex (ACC) in the affective
      component of pain. The aim of this study was to investigate the role of taurine
      as a glycinergic agonist in the ACC using a neuropathic pain model related to
      autotomy behaviour (AB). In order to test whether glyR(A) is responsible for
      taurine actions, we microinjected strychnine, a glyR(A) antagonist. We used
      taurine microinjected into the ACC, followed by a thermonociceptive stimulus and
      a sciatic denervation. Chronic nociception was measured by the autotomy score,
      onset and incidence. The administration of taurine 7 days after denervation
      modifies the temporal course of AB by inhibiting it. Our results showed a
      decreased autotomy score and incidence in the taurine groups, as well as a delay
      in the onset. Those experimental groups in which strychnine was microinjected
      into the ACC, either on its own or before the microinjection of taurine, showed
      no difference as compared to the control group. When taurine was microinjected
      prior to strychnine, the group behaved as if only taurine had been administered.
      Our results evidence a significant neuropathic nociception relief measured as an
      AB decrease by the microinjection of taurine into the ACC. Besides, the role of
      the glyR(A) is evidenced by the fact that strychnine antagonises the
      antinociceptive effect of taurine.

PMID- 16887372
TI  - Fgfrl1, a fibroblast growth factor receptor-like gene, is found in the
      cephalochordate Branchiostoma floridae but not in the urochordate Ciona
      intestinalis.
AB  - FGFRL1 is a novel member of the fibroblast growth factor receptor family that
      controls the formation of musculoskeletal tissues. Some vertebrates, including
      man, cow, dog, mouse, rat and chicken, possess a single copy the FGFRL1 gene.
      Teleostean fish have two copies, fgfrl1a and fgfrl1b, because they have undergone
      a whole genome duplication. Vertebrates belong to the chordates, a phylum that
      also includes the subphyla of the cephalochordates (e.g. Branchiostoma floridae)
      and urochordates (tunicates, e.g. Ciona intestinalis). We therefore investigated
      whether other chordates might also possess an FGFRL1 related gene. In fact, a
      homologous gene was found in B. floridae (amphioxus). The corresponding protein
      showed 60% sequence identity with the human protein and all sequence motifs
      identified in the vertebrate proteins were also conserved in amphioxus Fgfrl1. In
      contrast, the genome of the urochordate C. intestinalis and those from more
      distantly related invertebrates including the insect Drosophila melanogaster and
      the nematode Caenorhabditis elegans did not appear to contain any related
      sequences. Thus, the FGFRL1 gene might have evolved just before branching of the
      vertebrate lineage from the other chordates.

PMID- 16887373
TI  - Solitary plasmacytoma of bone in two successfully treated cats.
AB  - This is the first report of feline solitary plasmacytoma of bone. We describe the
      clinical, clinico-pathological, radiographic and pathological findings of two
      successfully treated cats with long-term follow-up. The first case presented with
      spinal pain and neurological deficits. Radiographs demonstrated sclerosis of
      lumbar vertebra L6 and a myelogram confirmed interference to flow of contrast in
      the L4-7 region. A biopsy of L6 revealed neoplastic plasma cell infiltration.
      There was no evidence of paraproteinaemia on serum protein electrophoresis. The
      cat underwent hypofractionated megavoltage radiotherapy. Clinical signs resolved
      completely and 4 years after diagnosis the cat remains well and has no
      electrophoretically detectable paraproteinaemia. The second case presented with
      neurological deficits of the tail and spinal radiographs revealed extensive
      osteolysis of the sacrum. A biopsy of sacral bone demonstrated neoplastic plasma
      cell infiltration. The animal was normoglobulinaemic. The cat improved clinically
      with induction chemotherapy (melphalan and methylprednisolone). The same
      chemotherapeutics were continued at maintenance doses for 4.3 years, at which
      time there was recurrence of neurological deficits and a palpable sacral mass.
      Cytological examination of a fine needle aspirate confirmed recurrence of plasma
      cell neoplasia. A low concentration monoclonal paraproteinaemia was detected.
      Vincristine was administered resulting in resolution of neurological deficits and
      a palpably smaller sacral mass. Eighteen months into vincristine therapy, there
      was recurrence of clinical signs and the cat was euthanased, more than 6 years
      after the initial diagnosis.

PMID- 16887374
TI  - Exploring the relationship between essential tremor and Parkinson's disease.
AB  - Although essential tremor (ET) and Parkinson's disease (PD) are considered
      distinct disorders, there is overlap in some clinical features. In some PD
      patients, a long-standing postural tremor in the hands may precede the onset of
      parkinsonian features by several years or decades. Furthermore, large families
      with both ET and PD phenotypes have been described and autopsy studies have
      demonstrated Lewy body pathology in brains of ET patients. Functional
      neuroimaging suggests that some ET patients have dopaminergic deficit. We examine
      here the evidence for and against an association between ET and PD, and
      critically review data supporting the notion that a subset of ET patients is
      predisposed to developing PD.

PMID- 16887375
TI  - Robust mosaicing with correction of motion distortions and tissue deformations
      for in vivo fibered microscopy.
AB  - Real-time in vivo and in situ imaging at the cellular level can be achieved with
      fibered confocal microscopy. As interesting as dynamic sequences may be, there is
      a need for the biologist or physician to get an efficient and complete
      representation of the entire imaged region. For this demand, the potential of
      this imaging modality is enhanced by using video mosaicing techniques. Classical
      mosaicing algorithms do not take into account the characteristics of fibered
      confocal microscopy, namely motion distortions, irregularly sampled frames and
      non-rigid deformations of the imaged tissue. Our approach is based on a
      hierarchical framework that is able to recover a globally consistent alignment of
      the input frames, to compensate for the motion distortions and to capture the non
      rigid deformations. The proposed global alignment scheme is seen as an estimation
      problem on a Lie group. We model the relationship between the motion and the
      motion distortions to correct for these distortions. An efficient scattered data
      approximation scheme is proposed both for the construction of the mosaic and to
      adapt the demons registration algorithm to our irregularly sampled inputs.
      Controlled experiments have been conducted to evaluate the performance of our
      algorithm. Results on several sequences acquired in vivo on both human and mouse
      tissue also demonstrate the relevance of our approach.

PMID- 16887376
TI  - Statistical representation of high-dimensional deformation fields with
      application to statistically constrained 3D warping.
AB  - This paper proposes a 3D statistical model aiming at effectively capturing
      statistics of high-dimensional deformation fields and then uses this prior
      knowledge to constrain 3D image warping. The conventional statistical shape model
      methods, such as the active shape model (ASM), have been very successful in
      modeling shape variability. However, their accuracy and effectiveness typically
      drop dramatically in high-dimensionality problems involving relatively small
      training datasets, which is customary in 3D and 4D medical imaging applications.
      The proposed statistical model of deformation (SMD) uses wavelet-based
      decompositions coupled with PCA in each wavelet band, in order to more accurately
      estimate the pdf of high-dimensional deformation fields, when a relatively small
      number of training samples are available. SMD is further used as statistical
      prior to regularize the deformation field in an SMD-constrained deformable
      registration framework. As a result, more robust registration results are
      obtained relative to using generic smoothness constraints on deformation fields,
      such as Laplacian-based regularization. In experiments, we first illustrate the
      performance of SMD in representing the variability of deformation fields and then
      evaluate the performance of the SMD-constrained registration, via comparing a
      hierarchical volumetric image registration algorithm, HAMMER, with its SMD
      constrained version, referred to as SMD+HAMMER. This SMD-constrained deformable
      registration framework can potentially incorporate various registration
      algorithms to improve robustness and stability via statistical shape constraints.

PMID- 16887377
TI  - Genotoxic evaluation of workers employed in pesticide production.
AB  - Pesticides are widely used throughout the world in agriculture to protect crops
      and in public health to control diseases. Nevertheless exposure to pesticides can
      represent a potential risk to humans. Pesticide manufacturing unit workers are
      prone to possible occupational pesticide exposure. Therefore, this study was
      performed to evaluate the genotoxic effect of pesticide exposure in these
      workers. In the present investigation 54 pesticide workers and an equal number of
      control subjects were assessed for genome damage in blood lymphocytes utilizing
      the chromosomal aberration analysis and the buccal epithelial cell by adopting
      the micronucleus test. The results suggested that pesticide workers had a
      significantly increased frequency of chromosomal aberrations when compared with
      controls (mean+/-S.D., 8.43+/-2.36 versus 3.32+/-1.26; P<0.05). Similarly, the
      pesticides exposed workers showed a significant increase in micronucleated cells
      compared with controls (1.24+/-0.72 versus 0.32+/-0.26; P<0.05). Analysis of
      variance revealed that occupational exposure to pesticides had a significant
      effect on frequency of micronuclei (P<0.05), whereas smoking, age, gender and
      alcohol consumption had no significant effect on genetic damage (P>0.05).
      However, no association was found between years of exposure, smoking, age,
      gender, alcohol consumption and higher levels of genetic damage as assessed by
      the chromosomal aberration assay (P>0.05). Our findings indicate that
      occupational exposure to pesticides could cause genome damage in somatic cells.

PMID- 16887379
TI  - Nutritional supplement chromium picolinate generates chromosomal aberrations and
      impedes progeny development in Drosophila melanogaster.
AB  - Chromium picolinate, [Cr(pic)(3)], is a popular nutritional supplement found in a
      variety of consumer products. Despite its popularity, safety concerns over its
      use have arisen. The supplement has been shown to generate clastogenic damage,
      mitochondrial damage, oxidative damage, and mutagenic effects in cultured cells
      and oxidative DNA damage and lipid peroxidation in rats. Recently [Cr(pic)(3)]
      has been demonstrated to generate heritable genetic change and delays in progeny
      development in Drosophila melanogaster. Based on the damage to chromosomes of
      cultured cells and of animal models, similar chromosome damage appeared to be a
      likely source of the mutagenic effects of the supplement in Drosophila. The
      current three-part study examines the effects of several chromium-containing
      supplements and their components on hatching and eclosion rates and success of
      development of first generation progeny of adult Drosophila fed food containing
      these compounds. It further examines the effects of the compounds on longevity of
      virgin male and female adults. Finally, the chromosomes in the salivary glands of
      Drosophila late in the third instar larval stage, which were the progeny of
      Drosophila whose diets were supplemented with nutritional levels of [Cr(pic)(3)],
      are shown to contain on average over one chromosomal aberration per two
      identifiable chromosomal arms. No aberrations were observed in chromosomes of
      progeny of untreated flies. The results suggest that human consumption of the
      supplement should be a matter of concern and continued investigation to provide
      insight into the requirements of chromium-containing supplements to give rise to
      genotoxic effects.

PMID- 16887378
TI  - Genotoxicity of industrial wastewaters obtained from two different pollution
      sources in northern India: a comparison of three bioassays.
AB  - The genotoxicity of industrial wastewater samples from Aligarh and Ghaziabad
      cities was compared using the Ames plate incorporation test, the Ames fluctuation
      test and the Allium cepa test. While TA102 and TA104 strains exhibited the
      highest sensitivity against the Aligarh sample (AWW) in terms of the slope (m) of
      the dose-response curve in the plate incorporation assay, TA98 and TA97a were the
      most sensitive strains based on the induction factor, Mi(p). TA98 once again, was
      the most sensitive strain against the test sample from Ghaziabad (GWW) in terms
      of 'Mi(p)' while TA102 was the most sensitive strain on the basis of the slope
      (m). TA100 displayed the highest susceptibility towards the samples from Aligarh
      in the fluctuation test. However, TA102 and TA98 responded maximally to GWW in
      this bioassay. The mutagenicity of the test samples seemed to be partly mediated
      by reactive oxygen species (ROS) as evidenced by the use of free radical
      scavengers. Mannitol brought about the maximum decline in the number of
      revertants of TA102 by the Aligarh sample, whereas such a reduction in case of
      Ghaziabad sample was exhibited with superoxide dismutase. Both the test water
      samples induced various anaphase aberrations in the root cells of Allium cepa.
      Fragmentation of the chromosome was the predominant effect of the Aligarh water
      sample while the Ghaziabad sample induced chromosome stickiness. The crucial
      roles of heavy metals and pesticides in the genotoxicity of AWW and GWW,
      respectively, have been suggested. In view of the problem associated with the
      interpretations of data, we recommend that all the test bioassays should be
      carried out in the presence of ROS scavengers for the fool proof evaluation of
      the genotoxicity of water samples.

PMID- 16887380
TI  - On the use of bipolar montages for time-series analysis of intracranial
      electroencephalograms.
AB  - OBJECTIVE: Bipolar montages are routinely employed for the interpretation of
      scalp and intracranial EEGs (icEEGs). In this manuscript we consider the
      assumptions that support the use of a bipolar montage and question the universal
      appropriateness of bipolar representation of icEEGs for the time-series analysis
      of these signals. Bipolar montages introduce an element of spatial processing
      into the observed time-series. In the case of icEEGs, we argue ambiguity may be
      introduced in some settings through this operation because of a lack of
      certifiability of local differentiability and continuity of the spatial structure
      of icEEGs, and their suboptimal spatial sampling. METHODS: Example icEEGs were
      collected from three patients being studied for possible resective epilepsy
      surgery. Referential and bipolar representations of these signals were subjected
      to different visual and time-series analysis. The time-series measures calculated
      were the power spectral density and magnitude squared coherence. RESULTS: Visual
      analysis and time-series measures revealed that the icEEG time-series was altered
      by the use of a bipolar montage. The changes resulted from either the
      introduction of unrelated information from the two referential time-series into
      the bipolar time-series, or from the removal or alteration of information common
      to the two referential time-series in the bipolar time-series. The changes could
      not be predicted without prior knowledge of the relationship between measurement
      sites that form the bipolar montage. CONCLUSIONS: In certain settings, bipolar
      montages alter icEEGs and can confound the time-series analysis of these signals.
      In such settings, bipolar montages should be used with caution in the time-series
      analysis of icEEGs. SIGNIFICANCE: This manuscript addresses the representation of
      the intracranial EEG for time-series analysis. There may be contexts where the
      assumptions underpinning correct application of the bipolar montage to the
      intracranial EEG are not satisfied.

PMID- 16887381
TI  - Enhanced magnetic auditory steady-state response in early Alzheimer's disease.
AB  - OBJECTIVE: Previous studies have reported abnormalities in both spontaneous and
      evoked electromagnetic brain activity in Alzheimer's disease (AD). We studied the
      auditory steady-state response (SSR) which represents the net effect of entrained
      background activity and superimposed cortical evoked responses, in AD patients
      and healthy controls. METHODS: Whole-head magnetoencephalography (MEG) was used
      to measure SSR to monaural 40-Hz stimulation in AD patients and age-matched
      controls. Equivalent current dipoles (ECD) of the SSR were modeled in each
      hemisphere, and source amplitudes were compared between the two groups using time
      varying ECD models. RESULTS: Our results indicate that the SSR is significantly
      increased in AD patients with mild to moderate cognitive deterioration in
      comparison with healthy elderly subjects. CONCLUSIONS: Goal-directed functioning
      requires optimization of inhibitory and excitatory inputs in the cortex, allowing
      the adaptation of responsiveness to repetitive stimulation with low relevance.
      The present results suggest that this balance is impaired in AD, manifesting
      itself in decreased inhibition in cortical auditory processing and impaired
      adaptation of the stimulus-locked activity, probably due to abnormalities in
      cholinergic modulation. SIGNIFICANCE: MEG appears to be a sensitive tool to
      detect abnormalities of auditory processing already in early stages of AD.

PMID- 16887382
TI  - Oscillatory cortical activity related to voluntary muscle relaxation: influence
      of normal aging.
AB  - OBJECTIVE: In this study we aimed to investigate if there are age-related
      differences in cortical oscillatory activity induced by self-paced muscular pure
      relaxation in comparison with muscle contraction as reference movement. METHODS:
      Event-related (de)synchronization (ERD/ERS) have been recorded related to
      voluntary muscle contraction and relaxation in 10 young and 10 elderly right
      handed healthy subjects. The muscle relaxation task consisted in a voluntary
      relaxation of maintained wrist extension without any overt, associated muscle
      contraction. The muscle contraction task corresponded to a self-initiated brief
      wrist extension. RESULTS: In elderly subjects compared to young ones, mu and beta
      ERD preceding muscular relaxation was more widespread, beginning significantly
      earlier over contralateral frontocentral and parietocentral regions (p<0.05) as
      well as over ipsilateral regions (p<0.05). The beta synchronization was
      significantly attenuated (p<0.05). CONCLUSIONS: These results suggest an
      alteration of inhibitory motor systems and an altered post-movement somesthetic
      inputs processing with normal aging. These alterations were accompanied by
      compensatory mechanisms. SIGNIFICANCE: These age-related alterations during
      different phases of muscle relaxation could participate to explain global
      sensorimotor slowing observed with normal aging.

PMID- 16887384
TI  - Quantitative topographic differentiation of the neonatal EEG.
AB  - OBJECTIVE: To test the discriminatory topographic potential of a new method of
      the automatic EEG analysis in neonates. A quantitative description of the
      neonatal EEG can contribute to the objective assessment of the functional state
      of the brain, and may improve the precision of diagnosing cerebral dysfunctions
      manifested by 'disorganization', 'dysrhythmia' or 'dysmaturity'. METHODS: 21
      healthy, full-term newborns were examined polygraphically during sleep (EEG-8
      referential derivations, respiration, ECG, EOG, EMG). From each EEG record, two 5
      min samples (one from the middle of quiet sleep, the other from the middle of
      active sleep) were subject to subsequent automatic analysis and were described by
      13 variables: spectral features and features describing shape and variability of
      the signal. The data from individual infants were averaged and the number of
      variables was reduced by factor analysis. RESULTS: All factors identified by
      factor analysis were statistically significantly influenced by the location of
      derivation. A large number of statistically significant differences were also
      established when comparing the effects of individual derivations on each of the
      13 measured variables. Both spectral features and features describing shape and
      variability of the signal are largely accountable for the topographic
      differentiation of the neonatal EEG. CONCLUSIONS: The presented method of the
      automatic EEG analysis is capable to assess the topographic characteristics of
      the neonatal EEG, and it is adequately sensitive and describes the neonatal
      electroencephalogram with sufficient precision. SIGNIFICANCE: The discriminatory
      capability of the used method represents a promise for their application in the
      clinical practice.

PMID- 16887383
TI  - Low frequency rTMS of the SMA transiently ameliorates peak-dose LID in
      Parkinson's disease.
AB  - OBJECTIVE: To determine whether low-frequency repetitive transcranial magnetic
      stimulation (rTMS) may modulate l-DOPA-induced dyskinesia (LID) in dyskinetic
      Parkinson's disease (PD) patients. LID is a severe motor complication in advanced
      PD patients. The neural mechanisms involved in LID are not clear, and it is
      apparent that both an excessive decrease in internal pallidus firing and a
      modification and overactivation of cortical motor and premotor areas are involved
      in its pathogenesis. METHODS: Using low frequency 1Hz repetitive rTMS we
      investigated whether decrease of excitability of the supplementary motor area
      (SMA) may result in modification of LID in PD patients. Furthermore we tested
      whether it was possible to enhance and/or prolong the beneficial effects of the
      treatment with repeated sessions of stimulation. RESULTS: We observed that 1Hz
      rTMS induced a transient reduction of dyskinesias. A single session of rTMS
      improved LID, while repeated sessions of stimulation failed to enhance and/or
      prolong the beneficial effects of the procedure, without causing motor
      deterioration or other adverse effects. CONCLUSIONS: These results suggest that
      LID may depend on an increased excitability of the SMA. SIGNIFICANCE: SMA rTMS is
      effective in reducing transiently LID, although cannot yet be considered
      clinically useful.

PMID- 16887385
TI  - Pre-movement modulation of tibial nerve SEPs caused by a self-initiated
      dorsiflexion.
AB  - OBJECTIVE: To investigate the centrifugal effect on somatosensory evoked
      potentials (SEPs), we recorded the pre-movement modulation of SEPs following
      stimulation of the tibial nerve caused by a self-initiated dorsiflexion. METHODS:
      SEPs following stimulation of the right tibial nerve at the popliteal fossa were
      recorded during self-initiated dorsiflexion of the right ankle every 5-7s. Based
      on the onset of Bereitschaftspotential and negative slope, the preparatory period
      before dorsiflexion was divided into four sub-periods (pre-BP, BP1a, BP1b and BP2
      sub-period), and SEPs in each sub-period were averaged. SEPs were also recorded
      in a stationary condition. RESULTS: P30, N40, P50 and N70 were identified at Cz
      in all subjects. The amplitude of P30 was significantly smaller in the BP2 sub
      period than in the pre-BP sub-period. The N40 amplitude was significantly
      attenuated in the BP2 sub-period compared with the stationary condition, the pre
      BP sub-period, the BP1a sub-period and the BP1b sub-period. CONCLUSIONS: These
      results suggested that the motor-related areas involved in generating negative
      slope modulated the tibial nerve SEPs preceding a self-initiated contraction of
      the agonist muscle. SIGNIFICANCE: The centrifugal gating effect on SEPs extends
      to the somatosensory information from the antagonistic body part.

PMID- 16887386
TI  - Peripheral median nerve block impairs precision pinch movement.
AB  - OBJECTIVE: The objective of this study was to investigate the effects of a
      simulated peripheral median nerve lesion on precision pinch movement by the thumb
      and index finger. METHODS: A median neuropathy was created by blocking the median
      nerve at the wrist using an anesthetic. The subjects (n=5) were asked to perform
      pulp-to-pulp precision pinch movements before and after the nerve block. Digit
      motion data was obtained with a marker-based motion analysis system. RESULTS: The
      radial offset of the thumb tip, as defined by the minimum distance of the thumb
      tip to the flexion-extension plane of the index finger, showed an increase of
      11.2mm after the nerve block. For the thumb, the nerve block caused a decrease in
      the range of motion at the metacarpophalangeal (MCP) joint, and a compensatory
      increase in the range of motion at the interphalangeal (IP) joint. The range of
      motion ratio (MCP:IP) changed from 1:4.8 (pre-block) to 1:1.0 (post-block). The
      maximum flexion angle at the MCP joint increased from 18.8 degrees (pre-block) to
      33.7 degrees (post-block), and maximum flexion angle at the IP joint decreased
      from 42.6 degrees (pre-block) to 18.8 degrees (post-block). For the index finger,
      the nerve block caused a decrease in the range of motion at the MCP joint, and
      compensatory increases in the ranges of motion at the proximal and distal
      interphalangeal (PIP and DIP) joints. The range of motion ratio (MCP:PIP:DIP)
      changed from 1:1.1:0.7 (pre-block) to 1:2.4:1.8 (post-block). The maximum flexion
      angle at the MCP joint decreased from 56.8 degrees (pre-block) to 34.6 degrees
      (post-block), and the maximum flexion angle at the PIP joint increased from 51.2
      degrees (pre-block) to 76.0 degrees (post-block), but the change at the DIP joint
      was insignificant. CONCLUSIONS: The median nerve block caused remarkable
      degradation of the pinch performance as quantified by an inaccurate pulp-to-pulp
      contact of the thumb to the index finger and an alteration of joint motion of the
      digits. SIGNIFICANCE: Many fine manual tasks require accurate pulp-to-pulp
      positioning of the thumb to the index finger. Within the hand, the median nerve
      is critical to the fine sensorimotor function due to the motor supply and the
      sensory endings to the thumb and index finger. People with median neuropathies
      (for example, carpal tunnel syndrome) experience clumsiness while performing
      simple manual tasks. The current approach to the examination of precision pinch
      movement may be utilized to quantify the apparent hand clumsiness observed in
      individuals with peripheral neuropathy such as carpal tunnel syndrome.

PMID- 16887387
TI  - Clinical trials update from the European Society of Cardiology heart failure
      meeting: TNT subgroup analysis, darbepoetin alfa, FERRIC-HF and KW-3902.
AB  - This article provides information and a commentary on trials relevant to the
      pathophysiology, prevention and treatment of heart failure, presented at the
      European Society of Cardiology heart failure meeting held in June 2006. All
      reports should be considered as preliminary data, as analyses may change in the
      final publication. In a sub-group analysis of the TNT study, intensive treatment
      with high-dose atorvastatin significantly reduced hospitalisations for heart
      failure in patients with stable coronary heart disease, compared with low-dose
      atorvastatin; this benefit was most evident in patients with a history of heart
      failure at baseline. In a combined analysis of two studies of darbepoetin alfa,
      which included 475 patients, treatment increased and maintained haemoglobin
      levels and produced non-significant improvements in symptoms and morbidity in
      anaemic heart failure patients compared to placebo. In the FERRIC-HF study
      (n=35), intravenous iron sucrose therapy improved exercise capacity and symptom
      status in iron-deficient heart failure patients. In a combined analysis of two
      studies (n=186), the adenosine A(1) receptor antagonist KW-3902 showed diuretic
      properties and appeared to enhance response to loop diuretics in heart failure
      patients hospitalised with fluid overload.

PMID- 16887388
TI  - Biotechnology SMEs, start-ups, spin-offs or microenterprises are they molecules
      coming from the research results? If so, what place do they hold in the global
      industrial tissue?
AB  - In recent years, the number of biotech enterprises in Europe has grown
      spectacularly, largely fueled by the increasing number of entrepreneurial
      initiatives from Europe's leading research institutes. The place held on the
      economic market by these enterprises, is a question that market analysts have
      been asking themselves since their rapid growth and, more particularly, their
      over valuation which, at times, has led to the crash of their shares on the stock
      markets. To be sure, this article does not claim to go into an in-depth financial
      analysis to explain the details of certain "shipwrecks". Rather, it just would
      like to provide some useful indications for all those having embarked, or
      desirous of doing so, in the creation of biomedical enterprises.

PMID- 16887390
TI  - Complete sequence of the large virulence plasmid pSFO157 of the sorbitol
      fermenting enterohemorrhagic Escherichia coli O157:H- strain 3072/96.
AB  - The large virulence plasmid pSFO157 of sorbitol-fermenting E. coli O157:H(-)
      strain 3072/96 has a size of 121,239bp and contains 96 open reading frames >50bp.
      It is therefore 29,162bp larger (ca. 32%) than plasmid pO157 of E. coli O157:H7
      strain EDL933. Major differences between the plasmids are the absence of katP,
      espP, and toxB in pSFO157 and, instead of these, the presence of the sfp fimbriae
      gene cluster and a large part of an F-plasmid transfer region, the latter
      accounting for most of the additional DNA. The differences in the order of the
      genes and their composition, as well as the presence of a number of replication
      associated genes and mobile genetic elements suggests that the large E. coli O157
      virulence plasmids have a complex evolutionary origin.

PMID- 16887389
TI  - Multiple cosmopolitan ecotypes within a microbial eukaryote morphospecies.
AB  - Microbial eukaryotes that are morphologically indistinguishable (i.e.
      'morphospecies') tend to be genetically diverse. While most protist morphospecies
      have cosmopolitan distribution, it has been suggested that ribotypes (unique rRNA
      gene sequences) or rRNA sequence clusters do have biogeography and such clusters
      may correlate with particular (non-morphological) adaptations. We have studied
      this in the ciliated protozoan morphospecies Cyclidium glaucoma. Fifty-four
      isolates collected worldwide represented 31 distinct ribotypes. There was no
      evidence of biogeographic distribution patterns. For example, identical ribotypes
      occurred in samples from Argentina, Peru, Morocco, Russia and Ukraine; in samples
      from Denmark and Australia; and in samples from Great Salt Lake and hyperhaline
      ponds in Spain. The morphospecies Cyclidium glaucoma is euryhaline and occurs in
      freshwater, brackish water, seawater, and hyperhaline waters. Evidence suggests
      that one ribotype cluster occurs only in marine or brackish habitats, and another
      one has so far been found only in hyperhaline habitats. Two clades seem to occur
      only in freshwater, but one clade includes ribotypes that were found in
      freshwater as well as in brackish water.

PMID- 16887392
TI  - The contributions of psychological disposition and risk factor status to health
      following treatment for coronary artery disease.
AB  - BACKGROUND: Successful adjustment following treatment for coronary artery disease
      is related to both psychological disposition and risk factor status.
      Consideration of the interplay between these variables is required to better
      acknowledge their relationship with health outcome. AIMS: To determine the
      salience of self-efficacy and locus of control to both general self-rated health
      and current cardiac health, relative to risk factor status. To determine whether
      self-efficacy is a more salient predictor of health status than locus of control.
      METHODS: Men (n=248) treated in the previous 3 years for either coronary artery
      disease alone or a myocardial infarction completed a questionnaire in which
      clinical, risk factor (knowledge of risk factors, current risk factors, change in
      risk factors), psychological (self-efficacy, locus of control) and health
      information were sought. RESULTS: Self-efficacy and internal locus of control had
      both direct and indirect influences on health in the models in which knowledge of
      risk factors was treated as the potential mediator. This pattern of results was
      not evident when either current risk factors or change in risk factors were
      examined as potential mediators. In the models in which self-efficacy was
      considered as a potential mediator of locus of control in the prediction of
      health status, self-efficacy was determined to be the more relevant psychological
      construct. CONCLUSION: The consistent positive associations obtained among self
      efficacy, cognitive risk factor status and health suggest that health
      professionals involved in cardiac rehabilitation should be encouraged to tailor
      interventions that allow patients to both improve their understanding of CAD and
      also to develop greater self-confidence in their ability to implement the
      acquired knowledge.

PMID- 16887391
TI  - The vertical distribution of house dust mite allergen in carpet and the effect of
      dry vacuum cleaning.
AB  - BACKGROUND: Carpets are large reservoirs of the dust mite allergen Der p 1. The
      effect of vacuum cleaning on the distribution of Der p 1 in carpets is poorly
      understood. METHODS: Samples were cut from 7 used household carpets, all over 5
      years of age. From each carpet, 10 samples were left untreated, 10 vacuumed with
      an upright vacuum cleaner, and 10 vacuumed with a canister vacuum cleaner. Each
      section was then cut into 3 horizontal layers: the top 2mm, the remainder of the
      carpet pile, and the carpet base. The mass of Der p 1 as a proportion of carpet
      volume was then determined. RESULTS: The concentrations of Der p 1 in each depth
      layer varied considerably between the 7 untreated carpets. In the top layer, Der
      p 1 concentrations were (median; 25th-75th percentiles): 41.9; 28.3-92.6 pg/mm3.
      For the middle layer they were similar (38.1; 22.4-108.5 pg/mm3), and for the
      carpet base, higher (212.4; 98.8-456.2 pg/mm3). In most cases, cleaning using
      either type of vacuum cleaner resulted in no significant reduction in allergen
      concentration throughout all depth layers. A subset of carpets showed an apparent
      increase in Der p 1 concentration in one or more layers following vacuum
      cleaning. In all tests Der p 1 was collected in the vacuum cleaners' filter bags.
      CONCLUSIONS: The depth-distribution of Der p 1 differs widely amongst used
      carpets. Vacuum cleaning changes the distribution of Der p 1 within such carpets
      but does not necessarily result in a reduction in the overall content.

PMID- 16887393
TI  - The challenge of implementing heart failure management programmes throughout
      Europe.

PMID- 16887395
TI  - Antiepileptic drug-induced mania in patients with epilepsy: what do we know?
AB  - Although mood disorders have a major impact on quality of life in patients with
      epilepsy, the nature of some aspects, such as mania, has received little
      attention. With the introduction of several new antiepileptic drugs into clinical
      practice, attention to psychiatric treatment-emergent adverse effects has been
      renewed. This article explores the relationship between antiepileptic drugs and
      mania in patients with epilepsy, with special emphasis on the clinical
      pathophysiology of this phenomenon.

PMID- 16887394
TI  - Modulation of ceramide metabolism enhances viral protein apoptin's cytotoxicity
      in prostate cancer.
AB  - Despite local and systemic therapies, the National Cancer Institute estimates
      that prostate cancer will cause over 30,000 deaths in 2006. This suggests that
      additional therapeutic approaches are needed. The chicken anemia viral protein
      Apoptin causes tumor-selective apoptosis in human tumor lines independent of p53
      and Bcl-2 status. Tet-regulated expression of Apoptin from an adenoviral vector
      showed cytotoxicity in DU145, PC-3, and LNCaP tumor cells regardless of
      expression of p53, Bcl-2, Bcl-xL, Bax, survivin, FLIP(S), XIAP, or CIAP. Apoptin
      expression caused an increase in the tumor suppressor lipid ceramide, which
      regulates the cellular stress response. Interestingly, 10 of 15 primary prostate
      cancers examined by Western blotting overexpressed acid ceramidase (AC),
      suggesting that ceramide deacylation might serve to negate elevated levels of
      ceramide, creating a more antiapoptotic phenotype. This was confirmed in AC
      overexpressing cells in which we observed decreased sensitivity to apoptosis
      following treatment with Apoptin. Addition of the AC inhibitor LCL204, in
      combination with Apoptin, augmented cell killing. This effect was also
      demonstrated in vivo in that Apoptin and LCL204 cotreatment significantly reduced
      tumor growth in DU145 xenografts (P<0.05). Taken together, our data demonstrated
      that Apoptin is a promising therapeutic agent for prostate cancer and that its
      function is improved when combined with acid ceramidase inhibitors.

PMID- 16887396
TI  - Arachnid lipoproteins: comparative aspects.
AB  - Findings on hemolymph lipoproteins in the class Arachnida are reviewed in
      relation to their lipid and protein compositions, hydrated densities, the
      capacity of apoproteins to bind lipids, and the influence of xenobiotics on their
      structures and functionality. The occurrence of hemolymphatic lipoproteins in
      arachnids has been reported in species belonging to the orders Araneida,
      Scorpionida, Solpugida and Acarina. However, lipoproteins were properly
      characterized in only three species, Eurypelma californicum, Polybetes
      pythagoricus and Latrodectus mirabilis. Like insect and crustaceans the arachnids
      examined contain high density lipoproteins (HDLs) as predominant circulating
      lipoproteins. Although in most arachnids these particles resemble those of insect
      HDLs called "lipophorins", in two arachnid species they differ from lipophorins
      in their apoproteins, total mass and lipid composition. The hemolymph of P.
      pythagoricus and L. mirabilis contains another HDL of higher density, while P.
      pythagoricus and E. californicum hemolymph contain a third lipoprotein of very
      high density (VHDL). Composition of arachnid lipoproteins regarding apoprotein
      classes as well as lipid classes differ among species. Hemocyanin, in addition to
      the classical role of this protein as respiratory pigment, is presented here
      performing the function of apolipoprotein in some arachnid species. Reports on
      experiments demonstrating the capacity of hemocyanin to bind neutral and polar
      lipid classes, including ecdysteroids, are commented. Recent works about the
      changes evoked by a phosphorous pesticide on the structures and functionality of
      spider lipoproteins are also reviewed.

PMID- 16887397
TI  - Corrosion evaluation of Ti-48Al-2Cr-2Nb (at.%) in Ringer's solution.
AB  - The corrosion behavior of Ti-48Al-2Cr-2Nb (at.%) in Ringer's solution was studied
      to evaluate its potential as a biocompatible material. Corrosion properties of Ti
      6Al-4V were determined under the same conditions for comparison. Two
      electrochemical techniques, potentiodynamic anodic polarization and
      electrochemical impedance spectroscopy, were employed to test Ti-48Al-2Cr-2Nb and
      Ti-6Al-4V. Surface modifications to the samples were made by autoclaving and by
      oxidation in air at 500 degrees C and 800 degrees C. The results show excellent
      corrosion resistance for unmodified Ti-48Al-2Cr-2Nb, corroborated by the high
      values of polarization resistance and corrosion potential and low values of
      corrosion current and corrosion rate. Ti-48Al-2Cr-2Nb appears to possess
      corrosion characteristics similar to Ti-6Al-4V. Surface modification rendered the
      Ti-48Al-2Cr-2Nb material extremely corrosion resistant.

PMID- 16887398
TI  - Abstracts from the International Conference on Progress in Bone and Mineral
      Research. November 16-18, 2006. Vienna, Austria.

PMID- 16887399
TI  - A case of tuberculous pericarditis: a rare but deadly disease.

PMID- 16887400
TI  - Rituximab-induced elimination of acquired angioedema due to C1-inhibitor
      deficiency.

PMID- 16887401
TI  - Severe hepatic injury caused by orlistat.

PMID- 16887402
TI  - Isopropyl alcohol-induced pseudo-azotemia: taking advantage of a laboratory
      error.

PMID- 16887403
TI  - Online buyers beware: a warning for physicians and patients.

PMID- 16887404
TI  - Systematic review and meta-analysis of adverse events of low-dose aspirin and
      clopidogrel in randomized controlled trials.
AB  - PURPOSE: We performed a systematic review to define the relative and absolute
      risk of clinically relevant adverse events with the antiplatelet agents, aspirin
      and clopidogrel. MATERIALS AND METHODS: Databases were searched for randomized
      controlled trials of low-dose aspirin (75-325 mg/day) or clopidogrel administered
      for cardiovascular prophylaxis. Relative risks (RR) were determined by meta
      analysis of 22 trials for aspirin versus placebo and from single studies for
      aspirin versus clopidogrel, aspirin versus aspirin/clopidogrel, and clopidogrel
      versus aspirin/clopidogrel. Absolute risk increase was calculated by multiplying
      RR increase by the pooled weighted incidence of the control. RESULTS: Aspirin
      increased the risk of major bleeding (RR=1.71; 95% confidence interval [CI], 1.41
      2.08), major gastrointestinal (GI) bleeding (RR=2.07; 95% CI, 1.61-2.66), and
      intracranial bleeding (RR=1.65; 95% CI, 1.06-5.99) versus placebo. No difference
      between 75-162.5 mg/day and >162.5-325 mg/day aspirin versus placebo was seen.
      The absolute annual increases attributable to aspirin were major bleeding: 0.13%
      (95% CI, 0.08-0.20); major GI bleeding: 0.12% (95% CI, 0.07-0.19), intracranial
      bleeding: 0.03% (95% CI, 0.01-0.08). No study compared clopidogrel with placebo.
      One study showed increased major GI bleeding (but not non-GI bleeding endpoints)
      with aspirin versus clopidogrel (RR=1.45; 95% CI, 1.00-2.10). The absolute annual
      increase was 0.12% (95% CI, 0.00-0.28). CONCLUSIONS: Low-dose aspirin increases
      the risk of major bleeding by approximately 70%, but the absolute increase is
      modest: 769 patients (95% CI, 500-1250) need to be treated with aspirin to cause
      one additional major bleeding episode annually. Compared with clopidogrel,
      aspirin increases the risk of GI bleeding but not other bleeding; however, 883
      patients (95% CI, 357-infinity) would need to be treated with clopidogrel versus
      aspirin to prevent one major GI bleeding episode annually at a cost of over 1
      million dollars.

PMID- 16887405
TI  - Pulmonary adverse events of anti-tumor necrosis factor-alpha antibody therapy.
AB  - It is well established that anti-tumor necrosis factor-alpha (TNFalpha) antibody
      is an efficacious disease-modifying drug for rheumatoid arthritis and Crohn's
      disease. Unfortunately, its long-term use can be associated with ominous
      pulmonary adverse events, most notably mycobacterial and fungal lung infections.
      To this end, reactivation of latent tuberculosis infection represents a serious
      concern of anti-TNFalpha antibody therapy. Given the anticipated increase in the
      approved indications for these drugs, community-based physicians should be made
      aware of these events for implementation of better patient selection for anti
      TNFalpha antibody therapy and initiation of appropriate measures once these
      adverse events are observed. This review will address this issue by outlining: 1)
      the role of TNFalpha in host inflammatory response to injury, particularly during
      mycobacterial and fungal infections; 2) the salutary effects of anti-TNFalpha
      antibody therapy in human diseases; and 3) the ominous pulmonary adverse events
      associated with these drugs.

PMID- 16887406
TI  - An Intranet-based system for inpatient billing in an academic medical center.
AB  - Academic physicians face great economic challenges. There is therefore a growing
      need to increase the efficiency of academic practice. One potential target for
      improving the "business" of medicine is inpatient billing. Currently many
      academic centers use "yellow" cards for inpatient billing. This is an inefficient
      system for capturing patient charges. We describe an Intranet-based system for
      inpatient billing that improves physician "productivity," reduces billing lag
      time, and increases the collection rate and total revenues.

PMID- 16887407
TI  - A necessary detour.

PMID- 16887408
TI  - It's all connected.

PMID- 16887409
TI  - Skin tears?

PMID- 16887410
TI  - Why is she fainting?

PMID- 16887411
TI  - An exotic bloom.

PMID- 16887412
TI  - Do patients with diabetes and low socioeconomic status receive less care and have
      worse outcomes? A national study.
AB  - PURPOSE: The objective of the study was to assess the influence of socioeconomic
      status (SES) on the care of patients with diabetes. METHODS: Quality indicators
      for patients who were taking medication for diabetes were established. Overall
      compliance with the quality indicators, as well as prevalence of diabetes by age,
      were obtained from a national database. Patients with national tax exemptions
      (used as a marker for low SES) were compared to those without. RESULTS: Of
      4,110,852 citizens aged 18-74, 210,988 (5.1%) were receiving medication for
      diabetes. The prevalence of diabetes reached 19.9% in people aged 65-74. 495,392
      citizens had an exemption, and they had a higher prevalence of diabetes that
      those who did not (15.4% vs. 3.7%). Patients with an exemption had a higher rate
      of having a yearly HbA1c done, a yearly LDL level done, a yearly eye exam, a
      yearly urinary protein exam, of being treated with insulin for an elevated HbA1c
      than those without an exemption. In patients with an exemption there was a lower
      percentage with an HbA1c less than 7%, a higher percentage with an HbA1c greater
      than 9%, and a lower percentage with an LDL less than 130. Multivariate analysis
      showed that exemption status was a predictor of better performance on process
      measures (LDL test done, OR-1.03, 95% CI 1.01-1.06, HbA1c test done, OR 1.03, 95%
      CI- 1.01-1.05) and of worse outcomes (high LDL, OR 0.92, 95% CI, 0.90-0.95 and
      high HbA1c, OR, 0.85, 95% CI, 0.83-0.87). CONCLUSIONS: In a country with
      universal healthcare, patients from a lower SES had an increased prevalence of
      diabetes and had greater adherence to preventive healthcare measures However,
      they were less successful in meeting target treatment goals.

PMID- 16887413
TI  - Migraines, angiographic coronary artery disease and cardiovascular outcomes in
      women.
AB  - PURPOSE: There are conflicting data regarding the association between migraines
      and cardiovascular events. We evaluated the relationship between migraine
      headaches, angiographic coronary artery disease, and cardiovascular events in
      women. SUBJECTS AND METHODS: The Women's Ischemia Syndrome Evaluation (WISE)
      study is a National Heart, Lung and Blood Institute (NHLBI)-sponsored
      prospective, multicenter study aiming to improve ischemia evaluation in women. A
      total of 944 women presenting with chest pain or symptoms suggestive of
      myocardial ischemia were enrolled and underwent complete demographic, medical,
      and psychosocial history, physical examination, and coronary angiography testing.
      A smaller subset of 905 women, representing a mean age of 58 years, answered
      questions regarding a history of migraines. We prospectively followed 873 women
      for 4.4 years for cardiovascular events and all-cause mortality. RESULTS: Women
      reporting a history of migraines (n=220) had lower angiographic coronary severity
      scores, and less severe (> or = 70% luminal stenosis) angiographic coronary
      artery disease compared to women without a history of migraines (n=685). These
      differences remained statistically significant after adjustment for age and other
      important cardiac risk factors. On prospective follow-up of a median of 4.4
      years, women with a history of migraines were not more likely to have a
      cardiovascular event (hazard ratio [HR] 1.2; 95% confidence interval [CI], 0.93
      1.58) and migraines did not predict all-cause mortality (HR 0.96; 95% CI, 0.49
      1.99). CONCLUSION: Among women undergoing coronary angiography for suspected
      ischemia, those reporting migraines had less severe angiographic coronary artery
      disease. We could not support an association between migraines and cardiovascular
      events or death. Further research studying the common pathophysiology underlying
      migraines and cardiovascular disease is warranted.

PMID- 16887414
TI  - Contemporary management of dyslipidemia in high-risk patients: targets still not
      met.
AB  - PURPOSE: Our objective was to evaluate treatment patterns and the attainment of
      current National Cholesterol Education Program (NCEP)-recommended lipid targets
      in unselected high-risk ambulatory patients. METHODS: Between December 2001 and
      December 2004, the prospective Vascular Protection and Guidelines Oriented
      Approach to Lipid Lowering Registries recruited 8056 outpatients with diabetes,
      established cardiovascular disease (CVD), or both, who had a complete lipid
      profile measured within 6 months before enrollment. The primary outcome measure
      was treatment success, defined as the achievement of LDL-cholesterol<2.6 mmol/L
      (100 mg/dL) according to NCEP guidelines. We examined patient characteristics and
      use of lipid-modifying therapy in relation to treatment outcome, which included
      the recently proposed optional LDL-cholesterol target (<1.8 mmol/L [70 mg/dL])
      for very high-risk patients. RESULTS: Overall, 78.2% of patients were treated
      with a statin and 51.2% had achieved the recommended LDL-cholesterol target.
      Treatment success rate was highest in diabetic patients with CVD (59.6%),
      followed by nondiabetic patients with CVD (51.8%), and lowest (44.8%) in diabetic
      patients without CVD (P<.0001). Compared with untreated patients, those on
      statins were more likely to achieve target (34.4% vs 55.9%, P<.0001). Of the
      patients who failed to meet target, only 9.9% were taking high-dose statin, while
      29.3% were not prescribed any statin therapy. Among very high-risk patients,
      20.8% attained the optional LDL-cholesterol goal. In multivariable analysis,
      advanced age, male sex, diabetes, coronary artery disease, coronary
      revascularization, and use of statin were associated with treatment success (all
      P<.0001). CONCLUSION: Despite the well-established benefits of available lipid
      modifying drugs, current management of dyslipidemia continues to be suboptimal,
      with a substantial proportion of patients failing to achieve guideline
      recommended lipid targets. There remains an important opportunity to improve the
      quality of care for these high-risk patients.

PMID- 16887415
TI  - Predischarge C-reactive protein and 1-year outcome after acute coronary
      syndromes.
AB  - PURPOSE: To investigate the relationship between high-sensitivity C-reactive
      protein and cardiovascular events following acute coronary syndrome. METHODS:
      This nationwide, cross-sectional, prospective study involved 439 patients with an
      acute coronary syndrome who presented to the hospital within 24 hours of symptom
      onset. Patients with a concomitant inflammatory process were excluded.
      Predischarge C-reactive protein samples were measured using a high-sensitivity
      method in a core laboratory. The outcome was the composite of death, acute
      myocardial infarction, stroke/transient ischemic attack, urgent hospitalization
      for unstable angina, and urgent revascularization within 1 year. RESULTS: At 1
      year, event rates were 10.2% for the lowest, 8.2% for the middle, and 11.0% for
      the highest C-reactive protein tertiles (P = .75) with similar event-free
      survival (P = .70). The hazard ratio (HR) for event rates between the highest and
      lowest tertiles was 1.10 (95% confidence interval [CI]: 0.54 to 2.20) There was
      marked overlap of C-reactive protein values between patients with and without
      events (median [interquartile range]: 8.39 [3.27 to 32.63] vs 9.55 [4.07 to
      24.02], respectively; P = .91). C-reactive protein was not an independent
      predictor of 1-year events (HR for highest tertile: 1.19; 95% CI: 0.58 to 2.43; P
      = .64) and performed poorly on receiver operating characteristic curve analysis
      (C statistic = 0.51). CONCLUSION: Predischarge high-sensitivity C-reactive
      protein level is a poor predictor of cardiovascular events at 1 year after acute
      coronary syndrome.

PMID- 16887416
TI  - A randomized, double-blind, placebo-controlled trial of nutritional
      supplementation during acute illness.
AB  - PURPOSE: The study tested whether nutritional support of older patients during
      acute illness leads to a clinical benefit. METHODS: In this randomized, double
      blind, placebo-controlled study, we randomly assigned 445 hospitalized patients
      aged 65 to 92 years to receive either a normal hospital diet plus 400 mL oral
      nutritional supplements (223 subjects) or a normal hospital diet plus a placebo
      (222 subjects) daily for 6 weeks. The composition of the supplement was such as
      to provide 995 kcal of energy and 100% of the Reference Nutrient Intakes for
      vitamins and minerals for a healthy older person. Patients had three assessments:
      at baseline, at 6 weeks, and at 6 months post-randomization. Outcome measures
      were 6 months of disability, non-elective readmission and length of hospital
      stay, discharge destination, morbidity, and mortality. RESULTS: Randomization to
      the supplement group led to a significant improvement in nutritional status. Over
      6 months, 65 patients (29%) in the supplements group were readmitted to the
      hospital compared with 89 patients (40%) in the placebo group (adjusted hazard
      ratio 0.68 [95% confidence interval 0.49-0.94]). The mean length of hospital stay
      was 9.4 days in the supplements group compared with 10.1 days in the placebo
      group. Thirty-two people (14%) died in the supplement group compared with 19
      people (9%) in the placebo group at 6 months (adjusted hazard ratio 1.65 [95%
      confidence interval, 0.93-2.92]). CONCLUSION: Oral nutritional supplementation of
      acutely ill patients improved nutritional status and led to a statistically
      significant reduction in the number of non-elective readmissions.

PMID- 16887418
TI  - Low-level environmental exposure to lead and progressive chronic kidney diseases.
AB  - PURPOSE: To determine whether low-normal body lead burden (BLB) accelerates
      progressive renal insufficiency in nondiabetic patients with chronic kidney
      diseases (CKD). METHODS: One hundred eight CKD patients (serum creatinine between
      1.5 and 2.9 mg/dL) with low-normal BLB (<80 microg) and no lead exposure history
      were observed for 24 months. Following the observation, 32 patients with low
      normal BLB (> or =20 microg and <80 microg) were randomly assigned to chelation
      and control groups. The chelation group patients were given edetate calcium
      disodium (EDTA) chelation therapy for 3 months and repeated chelation therapy
      during the following 24 months to maintain their BLB below 20 mug, while the
      control group patients underwent placebo therapy. The primary endpoint was an
      increased serum creatinine level to 1.25 times the baseline value. The secondary
      endpoint was temporal changes in renal function. RESULTS: The primary endpoint
      occurred in 14 patients in the observation period. Baseline BLB was the important
      risk factor in determining progressive renal insufficiency. The mean glomerular
      filtration rate (GFR) change in the chelation group patients was 6.6+/-10.7
      mL/min/1.73m(2), compared with -4.6+/-4.3 mL/min/1.73 m2 in control group
      patients (P <.001) at the end of the intervention period. The mean decrease in
      GFR per year of chelation group patients was lower than that of control group
      patients during the repeated chelation period. CONCLUSION: Environmental exposure
      to lead, even at low level, may accelerate progressive renal insufficiency of
      nondiabetic patients with CKD.

PMID- 16887417
TI  - Long-term prognosis and causes of death in systemic lupus erythematosus.
AB  - PURPOSE: We studied survival rate, prognostic factors, and causes of death in
      patients with systemic lupus erythematosus (SLE), particularly focusing on the
      influence of disease severity. PATIENTS AND METHODS: A cohort of 207 consecutive
      Italian patients with SLE were prospectively studied. All prominent clinical and
      serologic parameters were evaluated and considered as prognostic risk factors.
      Causes of death were defined on the basis of clinical data and, when available,
      postmortem examination. Survival was calculated from the time of diagnosis by
      Kaplan-Meier method. RESULTS: A total of 17 of 207 patients died; causes of death
      were active disease manifestations in 35.3% of cases and complication of the
      disease or its treatment in 64.7% of cases. The survival rates at 5, 10, and 15
      years after the diagnosis were 96%, 93% and 76%, respectively. By multivariate
      analysis of the risk factors, a predictive model consisting of male gender,
      positive lupus anticoagulant, and "severe" SLE was identified. The survival curve
      of the patients with severe disease was similar to that of patients with mild
      disease until 10 to 15 years from the diagnosis. Thereafter the two curves tended
      to diverge, showing a clear survival decline in patients with severe disease.
      CONCLUSIONS: Our study confirms the increase of short- and medium-term survival
      in patients with SLE, but long-term prognosis remains poor in patients with
      severe SLE manifestations.

PMID- 16887419
TI  - Paradoxical rebound platelet activation after painkillers cessation: missing risk
      for vascular events?
AB  - BACKGROUND: Several reliable reports strongly indicate that the use of
      nonsteroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase-2 (COX-2)
      inhibitors is associated with an increased risk of cardiovascular events.
      Considering the key role of platelets in coronary atherosclerosis and the fact
      that antiplatelet therapy with aspirin (and more recently, clopidogrel) has been
      associated with reduced vascular mortality, we sought to determine the effect of
      therapy and withdrawal of NSAIDs and COX-2 inhibitors on platelet activity.
      METHODS: Platelet characteristics from 34 aspirin-naive volunteers who were
      receiving NSAIDs and COX-2 inhibitors were compared with 138 drug-free controls.
      Platelets were assessed twice at baseline (at least 1 month of NSAIDs and COX-2
      inhibitors) and after a 14-day washout. We used adenosine diphosphate-induced
      conventional aggregometry, the point-of-care Ultegra analyzer (Ultegra
      Accumetrics, San Diego, Calif), and whole blood flow cytometry. RESULTS: Platelet
      activity during therapy with NSAIDs and COX-2 inhibitors was similar and
      unremarkable between groups. However, there was a highly significant increase of
      platelet activity as assessed by conventional aggregometry (P=.0003), Ultegra
      analyzer readings (P=.03), and expression of GPIIb/IIIa (P=.02), P-selectin
      (P=.03), and platelet endothelial cell adhesion molecule-1 (P=.001) after
      withdrawal from NSAIDs and COX-2 inhibitors. CONCLUSIONS: These data suggest that
      drug cessation, rather than continuous therapy with NSAIDs and COX-2 inhibitors,
      may be associated with rebound platelet activation, which may predispose one to a
      higher risk of vascular events. This hypothesis requires intensive testing in
      crossover randomized studies and may justify more aggressive antiplatelet
      regimens in patients after discontinuation of therapy with NSAIDs and COX-2
      inhibitors.

PMID- 16887420
TI  - Outcomes-based evaluation in resident education: creating systems and structured
      portfolios.

PMID- 16887422
TI  - Who's training whom?

PMID- 16887421
TI  - Initial successes and challenges in the development of a pediatric resident
      research curriculum.

PMID- 16887424
TI  - How low can we go...safely?: factors affecting intensive diabetes management.

PMID- 16887423
TI  - Neurodevelopmental impact of low-grade intraventricular hemorrhage in very
      preterm infants.

PMID- 16887425
TI  - No the evidence: what have measurements of exhaled nitric oxide got to offer?

PMID- 16887426
TI  - Autosomal recessive polycystic kidney disease and congenital hepatic fibrosis:
      summary statement of a first National Institutes of Health/Office of Rare
      Diseases conference.

PMID- 16887427
TI  - Beliefs about the appropriate age for initiating toilet training: are there
      racial and socioeconomic differences?
AB  - OBJECTIVE: To examine racial and socioeconomic differences in parental beliefs
      about the appropriate age at which to initiate toilet training. STUDY DESIGN: A
      cross-sectional survey of 779 parents visiting child health providers in 3
      clinical sites in Washington, DC and the surrounding metropolitan area completed
      a self-report survey. The main outcome variable was parental beliefs about the
      appropriate age at which to initiate toilet training. Using multiple linear
      regression, differences in beliefs were assessed in relation to race, family
      income, parental education, parental age, and age of the oldest and youngest
      children. RESULTS: Among respondents, parents felt that the average age at which
      toilet training should be initiated was 20.6 months (+/-7.6 months), with a range
      of 6 to 48 months. Caucasian parents believed that toilet training should be
      initiated at a significantly later age (25.4 months) compared with both African
      American parents (18.2 months) and parents of other races (19.4 months). In the
      multiple regression model, factors predicting belief in when to initiate toilet
      training were Caucasian race and higher income. CONCLUSIONS: Race and income were
      independent predictors of belief in age at which to initiate toilet training.
      More research is needed to determine what factors contribute to toilet training
      practices in diverse populations.

PMID- 16887428
TI  - Grades I-II intraventricular hemorrhage in extremely low birth weight infants:
      effects on neurodevelopment.
AB  - OBJECTIVE: To quantify the effect of grades I-II intraventricular hemorrhage
      (IVH) on the neurosensory and cognitive outcomes of extremely low birth weight
      infants. STUDY DESIGN: Of 706 extremely low birth weight infants without major
      malformations admitted to our center from 1992 to 2000, 537 survived to 20
      months' corrected age (CA) and had cranial ultrasound studies performed, of whom
      490 (91%) had complete neurodevelopmental assessments. Infants with severe
      cranial ultrasound abnormalities or meningitis were excluded, leaving a
      population of 362 infants, 258 of whom had a normal cranial ultrasound and 104
      had an isolated grade I-II IVH. The groups had similar birth weight (808 vs 801
      grams) and gestational age (26.5 vs 26.3 weeks). Outcomes of infants with normal
      cranial ultrasound were compared with those with grades I-II IVH at 20 months'
      CA. Outcomes included the Bayley Scales of Infant Development Mental
      Developmental Index (MDI) and major neurosensory abnormality. Logistic regression
      was used to assess the effect of grades I-II IVH on outcomes while adjusting for
      other risk factors. RESULTS: Extremely low birth weight infants with grades I-II
      IVH had a significantly lower mean MDI score than infants with normal cranial
      ultrasound (74 +/- 16 vs 79 +/- 14, P = .006). They had higher rates of MDI <<70
      (45% vs 25%; OR, 2.00; 95% CI, 1.20 to 3.30; P = .008), major neurologic
      abnormality (13% vs 5%; OR, 2.60; 95% CI, 1.06 to 6.36; P = .036), and
      neurodevelopmental impairment (47% vs 28%; OR, 1.83; 95% CI, 1.11 to 3.03; P =
      .018) at 20 months' CA, even when adjusting for confounding factors. CONCLUSIONS:
      Extremely low birth weight infants with grades I-II IVH have poorer
      neurodevelopmental outcomes at 20 months' CA than infants with normal cranial
      ultrasound. Advanced radiologic imaging may indicate additional brain injury
      associated with grade I-II IVH, which could explain these outcomes.

PMID- 16887429
TI  - Early bisphosphonate treatment in infants with severe osteogenesis imperfecta.
AB  - OBJECTIVE: To evaluate prospectively the efficacy of bisphosphonate treatment in
      infants with severe forms of osteogenesis imperfecta (OI). STUDY DESIGN: Of 10
      children (6 females) with OI type III, 5 (group A) started treatment (2 mg/kg
      neridronate administered intravenously for 2 consecutive days, every 3 months)
      just after diagnosis at birth and 5 (group B) after 6 months. Ten untreated
      children, matched for sex, age, and clinical severity of OI, constituted a
      historical control group (group C). We measured weight, length, and number of
      fractures every 3 months and serum and urinary levels of calcium, phosphorus,
      creatinine, serum alkaline phosphatase, 25-hydroxyvitamin D, insulin-like growth
      factor I, parathyroid hormone, and osteocalcin, urinary type I collagen N
      terminal telopeptide, and lateral radiography of vertebral column every 6 months.
      RESULTS: Group A had better growth and a lower incidence of fractures than groups
      B and C in the first 6 months of treatment. In the second 6 months, both groups A
      and B had lower fracture rates than group C. After 12 months of therapy,
      osteocalcin and insulin-like growth factor I levels significantly increased only
      in group A. The urinary Ca/Cr ratio and N-terminal telopeptide/Cr ratio
      significantly declined only in treated patients. Vertebral body area and the
      structure of vertebral bodies improved in all treated patients, but especially in
      group A. CONCLUSIONS: Cyclical neridronate treatment, started just after
      diagnosis at birth, had positive effects on growth and fracture rate.

PMID- 16887430
TI  - Theophylline for renal function in term neonates with perinatal asphyxia: a
      randomized, placebo-controlled trial.
AB  - OBJECTIVE: To study whether prophylactic theophylline can reduce the incidence
      and/or severity of renal failure in term infants with perinatal asphyxia. STUDY
      DESIGN: Term neonates with severe perinatal asphyxia were randomized to receive a
      single dose of either theophylline (study group, n = 40) or placebo (control
      group, n = 30) during the first hour of life. Daily weight, output/input ratio,
      24-hour fluid intake, and urine volumes were recorded during the first 5 days of
      life. Those infants with asphyxial renal failure were followed up for 1 year.
      RESULTS: The incidence of severe renal dysfunction was increased in the control
      group. Creatinine clearance was higher and excretion of beta 2 microglobulin
      (beta2M) was lower in the theophylline group. Conversely, the glomerular
      filtration rate was lower in the control group. In infants with renal failure,
      serum creatinine and creatinine clearance returned to normal in the neonatal
      period, and the increased beta2M excretion normalized by age 6 weeks.
      CONCLUSIONS: A single dose of theophylline within the first hour of birth in term
      neonates with perinatal asphyxia results in a significant decrease in serum
      creatinine level and urinary excretion of beta2M, along with an increase in
      creatinine clearance.

PMID- 16887431
TI  - The association of maternal overweight and obesity with breastfeeding duration.
AB  - OBJECTIVE: To determine whether maternal prepregnancy overweight or obesity has
      an independent effect on breastfeeding duration. STUDY DESIGN: A prospective
      birth cohort study of 1803 live-born children and their mothers ascertained
      through antenatal clinics at the major tertiary obstetric hospital in Perth,
      Australia, were followed until 3 years of age. Unconditional logistic, Cox
      regression, and Kaplan Meier analyses were used to model the association between
      maternal prepregnancy overweight and obesity and the duration of predominant or
      any breastfeeding allowing for adjustment of confounders (infant factors: gender,
      birth weight, gestational age, age solids introduced, and older siblings;
      maternal factors: smoking, education, age, race, marital status, pregnancy and
      birth complications, cesarean section, and socioeconomic status). RESULTS:
      Overweight and obese women were more likely to have discontinued breastfeeding at
      any time before 6 months than normal weight women (P < .0005) following
      adjustment for potential confounders. CONCLUSION: We have shown that prepregnancy
      body mass index is associated with reduced breastfeeding duration, and that
      mothers who are overweight or obese before pregnancy tend to breastfeed their
      infants for a shorter duration than normal weight mothers independent of maternal
      socioeconomic and demographic characteristics.

PMID- 16887432
TI  - Neurocognitive findings in Prader-Willi syndrome and early-onset morbid obesity.
AB  - OBJECTIVES: To examine whether early-onset morbid obesity is associated with
      cognitive impairment, neuropathologic changes, and behavioral problems. STUDY
      DESIGN: This case-control study compared head MRI scans and cognitive,
      achievement, and behavioral evaluations of subjects with Prader-Willi syndrome
      (PWS), early-onset morbid obesity (EMO), and normal-weight sibling control
      subjects from both groups. Head MRI was done on 17 PWS, 18 EMO, and 21 siblings,
      and cognitive, achievement, and behavioral evaluations were done on 19 PWS, 17
      EMO, and 24 siblings. RESULTS: The mean General Intellectual Ability score of the
      EMO group was 77.4 +/- 17.8; PWS, 63.3 +/- 14.2; and control subjects, 106.4 +/-
      13.0. Achievement scores for the three groups were EMO, 78.7 +/- 18.8; PWS, 71.2
      +/- 17.0; and control subjects, 104.8 +/- 17.0. Significant negative behaviors
      and poor adaptive skills were found in the EMO group. White matter lesions were
      noted on brain MRI in 6 subjects with PWS and 5 with EMO. None of the normal
      weight control subjects had these findings. CONCLUSIONS: Individuals with EMO
      have significantly lower cognitive function and more behavioral problems than
      control subjects with no history of childhood obesity. Both EMO and PWS subjects
      have white matter lesions on brain MRI that have not previously been described.

PMID- 16887433
TI  - Ghrelin levels in young children with Prader-Willi syndrome.
AB  - OBJECTIVE: To explore the hypothesis that high ghrelin levels contribute to
      obesity in Prader-Willi syndrome (PWS), we assessed whether the increased levels
      observed in older persons with PWS exist in very young children, before the onset
      of hyperphagia. STUDY DESIGN: We measured ghrelin levels in nine children with
      PWS (17-60 months of age) and eight healthy control subjects of equivalent body
      mass index (BMI), age, and sex. RESULTS: PWS and control groups had equivalent
      BMI (16.8 +/- 1.4 vs 16.1 +/- 0.9 kg/m(2), respectively; P = .24), age (37.8 +/-
      15.4 vs 50.3 +/- 17.7 months; P = .14), and sex. PWS and control groups also had
      equivalent fasting levels of total ghrelin (787 +/- 242 vs 716 +/- 135 pg/mL,
      respectively; P = .24), bioactive ghrelin (102 +/- 35 vs 91 +/- 23 pg/mL; P =
      .45), insulin, and glucose. Ghrelin correlated negatively with BMI among controls
      (r = -0.760, P = .029) but not PWS (r = 0.015, P = .97). CONCLUSIONS: Children <5
      years of age with PWS, who had not yet developed hyperphagia or excessive
      obesity, had normal ghrelin levels, in contrast with the hyperghrelinemia of
      older, hyperphagic people with PWS. It is possible that ghrelin levels increase
      suddenly before hyperphagia develops.

PMID- 16887435
TI  - Somatic growth after ventricular septal defect in malnourished infants.
AB  - OBJECTIVE: To assess somatic growth after ventricular septal defect (VSD) repair
      in severely malnourished infants. STUDY DESIGN: Ninety consecutive infants (age
      at surgery: 7.2 +/- 3.2 months) were followed after VSD closure at a referral
      center in southern India to evaluate somatic growth. RESULTS: At surgery, 44% and
      30% of patients had weight and height Z score <-3, respectively. On follow-up
      (age 5.4 +/- 0.8 years), despite a significant improvement from baseline (Z score
      -1.8 +/- 1.2 vs -2.8 +/- 1.3, P <.001), weight was significantly lower compared
      with healthy Indian children, particularly for boys. Height Z score improved
      significantly only in girls (-0.8 +/- 1.3 vs -1.8+/-2.1, P = .01). Weight,
      height, and combined weight and height Z scores (failure to thrive) of <-2 were
      observed in 42%, 27%, and 18 % of patients, respectively. On multivariate
      analysis, weight Z score <-2 on follow-up was predicted by weight Z score at
      surgery and male sex, height Z score <-2 by maternal height and male sex, and
      failure to thrive by maternal height and caloric intake. CONCLUSIONS: There is
      suboptimal recovery of somatic growth after repair of VSD in severely
      malnourished infants. Preoperative malnutrition affected only weight on follow
      up, whereas height recovery and failure to thrive were influenced by
      constitutional factors.

PMID- 16887436
TI  - Comparison of classifications for heart failure in children undergoing valvular
      surgery.
AB  - OBJECTIVES: To characterize correlations between clinical classifications of
      heart failure and diagnostic workup. STUDY DESIGN: Pre- and postoperative
      characteristics of 20 children with heart failure secondary to valvular rheumatic
      disease were studied. RESULTS: Both scoring systems correlated with N-terminal
      pro-brain natriuretic peptide (N-proBNP) but not with troponin I (TnI). The PHFI
      correlated with N-proBNP, end-systolic wall stress, left ventricular mass index
      and left atrium to aorta diameter ratio. No correlation could be established
      between modified Ross score, or the New York Heart Association (NYHA) grade and
      echocardiographic measurements. Cardiothoracic and Sokolow indexes were
      correlated with the PHFI as well as to the NYHA classification. CONCLUSION: In
      this study, PHFI seems better correlated with radiologic, electrocardiographic,
      echocardiographic, and biologic assessment of heart failure in children. Clinical
      severity was correlated with N-proBNP but not with TnI.

PMID- 16887437
TI  - Evaluation of gastroesophageal reflux in pediatric patients with asthma using
      impedance-pH monitoring.
AB  - OBJECTIVES: To determine the proportion of acid and nonacid reflux events in
      children with asthma suspected to have gastroesophageal reflux (GER) using
      combined impedance-pH monitoring, and to determine the symptom index (SI) for
      nonacid and acid reflux events. STUDY DESIGN: This was a prospective study of
      children with asthma (age 5 months to 6 years) referred for evaluation of GER.
      Exclusion criteria were congenital anomalies, cerebral palsy, mental retardation,
      and cardiac disease. The children underwent a 20-hour multichannel intraluminal
      impedance (MII)-pH study. RESULTS: A total of 24 children (17 male; mean age, 33
      months) were enrolled from March 2004 to February 2005. MII-pH detected 1184
      reflux events, versus 419 reflux events by pH alone; 51% (605 events) were
      nonacid. The proportion of nonacid reflux events decreased with time elapsed from
      last meal (P < .0001 by Pearson's chi2 test). A total of 555 symptoms were
      recorded, including 331 cases of cough, 243 of which (73.4%) were not associated
      with a reflux event. The SI for MII-pH was significantly different than that for
      the pH probe (37% vs 0%; P = .008). CONCLUSIONS: Acid and nonacid reflux occurs
      with equal frequency in children with asthma. Most symptoms occur in the absence
      of a reflux event.

PMID- 16887438
TI  - Environmental exposures and exhaled nitric oxide in children with asthma.
AB  - OBJECTIVE: To evaluate the relation of environmental factors with exhaled nitric
      oxide (FENO) concentrations among asthmatic children. STUDY DESIGN: Cross
      sectional analysis of 170 tobacco smoke-exposed children, ages 6 to 12 years, who
      have doctor-diagnosed asthma using measures of FENO, medication use, and
      exposures to settled indoor allergens and tobacco smoke. RESULTS: In
      multivariable analysis, child's age, uncarpeted flooring, not owning a cat,
      higher income, dust mite exposure, and being sensitized to any allergens were
      associated with higher FENO concentrations. Children who were sensitized to
      indoor allergens had an adjusted geometric mean FENO of 15.4 ppb (95% CI, 13.1,
      18.2) compared with 10 ppb (95% CI, 8.2, 12.2) for unsensitized children. There
      was no statistically significant association of serum cotinine, hair cotinine, or
      reported corticosteroid therapy with FENO. CONCLUSIONS: FENO is higher among
      children who are sensitized to indoor allergens and exposed to dust mites. The
      results hold promise for the use of FENO as a tool to manage childhood asthma by
      using both pharmacologic and environmental treatments.

PMID- 16887440
TI  - Optimal control of type 1 diabetes mellitus in youth receiving intensive
      treatment.
AB  - OBJECTIVE: To investigate the impact of factors that might interfere with optimal
      glycemic control in youth with type 1 diabetes mellitus (T1DM) in the current era
      of intensive management, including the interplay of race/ethnicity and
      socioeconomic status (SES) on HbA1c levels. STUDY DESIGN: This study comprised a
      database review of all patients under age 18 years with T1DM for at least 6
      months duration. Sex, age, race/ethnicity, duration of diabetes, mode of insulin
      administration (pump vs injection), body mass index, SES, and HbA1c level were
      recorded at each patient's most recent visit between January and September 2003.
      RESULTS: Mean HbA1c level for the 455 patients was 7.6% +/- 1.4%; only 31% of
      patients failed to meet the therapeutic goal of < 8.0%. Multiple linear
      regression analysis identified female sex (P = .02), older age (P = .001), longer
      duration of diabetes (P < .001), injection therapy (P < .001), and lower SES (P =
      .001) as significantly associated with higher HbA1c level. After adjustment for
      SES, race/ethnicity was not a determinant of HbA1c level. CONCLUSIONS: Low SES
      had a greater association with poor metabolic control than did race/ethnicity,
      which was not associated with differences in HbA1c level after controlling for
      SES. Most children were able to attain glycemic targets at least as good as the
      Diabetes Control and Complications Trial recommendations in a large clinical
      practice.

PMID- 16887441
TI  - Testicular microlithiasis in patients with Down syndrome.
AB  - OBJECTIVES: Testicular microlithiasis (TM) occurs with benign as well as with
      pathological conditions, such as testicular cancer. Since Down syndrome (DS) may
      be associated with increased frequency of testicular cancer, we determined the
      prevalence of TM in DS in patients from a DS clinic and evaluated the prevalence
      by age group. STUDY DESIGN: We compared results of research scrotal ultrasounds
      obtained from 1998 to 2001 from 92 Latino patients with DS (ages newborn to 29.7
      years) and clinical ultrasounds obtained from 1998 to 2004 from 200 Latino
      patients without DS (ages newborn to 18.3 years). We also reviewed the medical
      records. RESULTS: The prevalence of TM in DS was 29%, significantly higher than
      the 7% found in patients without DS (P < .0001). Twenty of the 27 patients with
      DS and TM had no testicular pathology clinically or by history. The TM prevalence
      in the entire group of patients with and without DS increased with advancing age.
      CONCLUSIONS: We found a significantly increased prevalence of TM in DS. The
      clinical significance of TM needs to be investigated further.

PMID- 16887442
TI  - Prediction of resistance to intravenous immunoglobulin treatment in patients with
      Kawasaki disease.
AB  - OBJECTIVES: The objective of this study was to find the predictors and generate a
      prediction score of resistance to intravenous immunoglobulin (IVIG) in patients
      with Kawasaki disease (KD). STUDY DESIGN: Patients diagnosed as having KD were
      sampled when they received initial high-dose IVIG treatment (2 g/kg dose) within
      9 days of illness (n = 320). These patients were divided into 2 groups: the
      resistance (n = 41) and the responder (n = 279). The following data were obtained
      and compared between resistance and responder: age, sex, illness days at initial
      treatment, and laboratory data. RESULTS: Multivariate logistic regression
      analysis identified age, illness days, platelet count, alanine aminotransferase
      (ALT), and C-reactive protein (CRP) as significant predictors for resistance to
      IVIG. We generated prediction score assigning 1 point for (1) infants less than 6
      months old, (2) before 4 days of illness, (3) platelet count <or= 30 x 10(10)/L,
      (4) CRP >or= 8 mg/dL, as well as 2 points for (5) ALT >or= 80 IU/L. Using a cut
      off point of 3 and more with this prediction score, we could identify the IVIG
      resistant group with 78% sensitivity and 76% specificity. CONCLUSIONS: Resistance
      to IVIG treatment can be predicted using age, illness days, platelet count, ALT,
      and CRP. Randomized, multicenter clinical trials are necessary to create a new
      strategy to treat these high-risk patients.

PMID- 16887444
TI  - Congenital localized scleroderma.
AB  - OBJECTIVES: Juvenile localized scleroderma (JLS) usually has its onset during
      later childhood. This report describes the clinical and serologic features of six
      children with congenital localized scleroderma (CLS). STUDY DESIGN: A large,
      multinational study was conducted among pediatric rheumatology and dermatology
      centers by collecting information on demographics, family history, triggering
      environmental factors, clinical features, laboratory reports, and treatment of
      patients with JLS. Patients with onset at birth were carefully examined. RESULTS:
      Among 750 patients with JLS, 6 patients (0.8%) had scleroderma-related lesions at
      birth. Female-to-male ratio was 2:1. All patients had linear scleroderma, in four
      involving the face with en coup de sabre appearance. Two patients were
      misdiagnosed as having skin infection, one nevus, one salmon patch, and two
      undefined skin lesions. The mean diagnostic delay was 3.9 years. In comparison
      with the group of 733 patients with late-onset JLS, CLS presented a significantly
      more prolonged disease duration at diagnosis and a higher frequency of en coup de
      sabre subtypes. CONCLUSIONS: Congenital localized scleroderma is a rare and
      probably underestimated condition in neonates. The linear subtype was the
      exclusive manifestation of the disease. CLS should be included in the
      differential diagnosis of infants with cutaneous erythematous fibrotic lesions to
      avoid functional and aesthetic sequelae and to allow prompt therapy.

PMID- 16887443
TI  - Early prednisone therapy in Henoch-Schonlein purpura: a randomized, double-blind,
      placebo-controlled trial.
AB  - OBJECTIVE: To evaluate the efficacy of early prednisone therapy in preventing
      renal and treating extrarenal and renal symptoms in Henoch-Schonlein purpura
      (HSP) in a placebo-controlled trial. STUDY DESIGN: A total of 171 patients (84
      treated with prednisone and 87 receiving placebo) were included and followed up
      for 6 months. The endpoints were renal involvement at 1, 3, and 6 months and
      healing of extrarenal symptoms. The analyses were performed on an intent-to-treat
      basis. RESULTS: Prednisone (1 mg/kg/day for 2 weeks, with weaning over the
      subsequent 2 weeks) was effective in reducing the intensity of abdominal pain
      (pain score, 2.5 vs 4.8; P = .029) and joint pain (4.6 vs 7.3; P = .030).
      Prednisone did not prevent the development of renal symptoms but was effective in
      treating them; renal symptoms resolved in 61% of the prednisone patients after
      treatment, compared with 34% of the placebo patients (difference = 27%; 95%
      confidence interval = 3% to 47%; P = .024). CONCLUSIONS: The general use of
      prednisone in HSP is not supported, but patients with disturbing symptoms may
      benefit from early treatment, because prednisone reduces extrarenal symptoms and
      is effective in altering (but not preventing) the course of renal involvement.

PMID- 16887445
TI  - Beyond psychopathology: assessing seriously disruptive students in school
      settings.
AB  - OBJECTIVE: To obtain a demographic profile of aggressive students in an urban
      setting and discern psychiatric diagnoses, functional impairment, and
      psychosocial stressors. STUDY DESIGN: Participants were 33 students in an urban
      public school district referred for comprehensive psychiatric evaluation by
      school staff because they were viewed as a threat to school safety. Evaluations
      included a review of records, interviews with school and mental health
      professionals, and student and parent interviews. RESULTS: Students were
      characterized by severe and untreated or undertreated psychopathology together
      with high levels of psychosocial stressors and learning disorders. Thirty-two
      students received at least one Axis I diagnosis, and the mean number of diagnoses
      for each student was 3; 33% had substance abuse problems, and 30% had
      nonpsychiatric medical conditions. CONCLUSIONS: The sample is a chronically
      impaired group of students confronting serious adversity in their daily lives,
      whose psychosocial and psychiatric needs are not met by current educational and
      mental health programming. Necessary interventions include prevention and early
      identification, substance abuse and family treatment, and appropriate
      psychopharmacological treatment. A comprehensive psychiatric assessment can help
      change the outcomes for this group of aggressive students.

PMID- 16887446
TI  - Validity of the revised Impact on Family (IOF) scale.
AB  - OBJECTIVE: To assess psychometric properties of the revised 15-item Impact on
      Family (IOF) Scale. STUDY DESIGN: A secondary analysis of items using data
      collected from 252 parents during an earlier randomized clinical trial. RESULTS:
      Exploratory factor analysis and confirmatory factor analysis identified a single
      factor with factor loadings similar to that of IOF developers. The one factor
      accounts for 45.7% of the sample variance. An Item Response Theory analysis found
      that 11 of the 15 items had alpha values greater than 1.00, with good to
      excellent item characteristic and item information curves. The test information
      and measurement error curves for the entire IOF were excellent. Construct
      validity of the IOF also was supported. Parent IOF scores correlated in the
      expected directions with maternal mood (r = -0.50), sibling behavior problems (r
      = -0.35), and severity of illness (r = 0.31) and were associated with family
      socioeconomic status (t = -4.5, all P < .001). CONCLUSIONS: This study provides
      independent support for validity and reliability of the revised IOF scale. This
      scale is a promising, easy-to-use instrument for the measurement of impact of
      illness and disability on families of children with chronic illness or
      disability.

PMID- 16887447
TI  - Pediatric workforce: a look at pediatric pulmonology data from the American Board
      of Pediatrics.

PMID- 16887449
TI  - Physician documentation of neonatal risk assessment for perinatal infections.
AB  - Charts of newborn infants were reviewed for documentation of maternal risk
      factors and prenatal screening test results. Physician documentation was
      incomplete in most infants. Nearly half of all infants were discharged without
      documentation regarding maternal status of hepatitis B, syphilis, and group B
      streptococcus. These lapses in newborn assessment have a potential for
      significant medical errors.

PMID- 16887450
TI  - Salt-wasting 21-hydroxylase deficiency congenital adrenal hyperplasia and pyloric
      stenosis in two Hispanic brothers.
AB  - The differential diagnosis of vomiting and dehydration in the first month of life
      includes congenital adrenal hyperplasia (CAH) and pyloric stenosis (PS). Each
      diagnosis may mask the presence of the other, requiring careful evaluation and
      follow-up. We document the occurrence of CAH and PS in two Hispanic siblings.

PMID- 16887451
TI  - Variable presentation of precocious puberty associated with the D564G mutation of
      the LHCGR gene in children with testotoxicosis.
AB  - We report on a family with familial male-limited precocious puberty (FMPP) due to
      a D564G mutation of the LHCGR gene. Family members show a varied phenotypic
      expression from severe precocity unresponsive to therapy with compromise of the
      predicted final height in some members, to attainment of tall final stature in
      other members who never received medical treatment. DNA amplification and
      sequencing of exon 11 of the LHCGR gene was done for the three affected male
      members and their mother. DNA analysis revealed a D564G mutation in the third
      cytoplasmic loop of the LHCGR receptor. All three males had precocious puberty
      with elevated testosterone levels. The index case developed central precocious
      puberty and evidence of compromised final height while on therapy. In contrast,
      the untreated older siblings attained a tall final height. This report
      underscores the possibility that the effects of the mutant luteinizing
      hormone/choriogonadotropin receptor on phenotypic expression of FMPP, such as
      adult final height, are modified by other factors.

PMID- 16887452
TI  - Pediatric reference intervals for uncommon bleeding and thrombotic disorders.
AB  - This study provides pediatric reference intervals and median values for factors
      II, V, VII, X, fibrinogen, alpha-2-antiplasmin (AP), antithrombin (AT),
      plasminogen, protein C (PC), and protein S (PS) for children 7 to 17 years of
      age. All analytes exhibited at least some age dependence in late childhood and
      adolescence either when compared against adult values or when medians for
      children were regressed against age.

PMID- 16887453
TI  - Accessory male pseudogenitalia?

PMID- 16887454
TI  - Non-traumatic nasopharyngeal suction in premature newborn infants with upper
      airway obstruction from secretions following nasal CPAP.

PMID- 16887455
TI  - The mitochondrial DNA A3243A>G mutation must be an infrequent cause of Asperger
      syndrome.

PMID- 16887456
TI  - More on oxygen and cancer.

PMID- 16887457
TI  - Chronic arthritis without uveitis in velocardiofacial syndrome.

PMID- 16887458
TI  - Reply to clonidine exposures, not toxicity.

PMID- 16887459
TI  - Fasting glucose is not useful in identifying obese white children with impaired
      glucose tolerance.

PMID- 16887460
TI  - Epileptiform discharges and the behavior of children with epilepsy.

PMID- 16887462
TI  - Propylthiouracil and antineutrophil cytoplasmic antibody associated vasculitis:
      the detective finds a clue.

PMID- 16887463
TI  - Propylthiouracil-induced autoimmune syndromes: two distinct clinical
      presentations with different course and management.
AB  - OBJECTIVES: To report 4 cases of propythiouracil (PTU)-induced lupus or
      vasculitis and to review the literature on that subject. METHODS: We describe the
      clinical presentation, course, and outcome of 4 patients and review the medical
      literature registered in the Medline PubMed database from 1966 to 2004 by using
      the keywords: Graves, thyrotoxicosis, propylthiouracil, lupus, vasculitis,
      arthritis, rash, ANA, and ANCA. Cases were classified into drug-induced lupus
      (DIL) or vasculitis using accepted definitions and evaluated with emphasis on
      gender, age, origin, duration of treatment, delay in diagnosis, clinical and
      serological features, and outcome. RESULTS: We described our 4 patients and
      analyzed 42 well-documented cases of DIL- and PTU-induced vasculitis (30 had
      vasculitis and 12 fulfilled the classification criteria of DIL). Patients with
      vasculitis were significantly older (mean 43 versus 22 years) and had a longer
      duration of treatment in comparison with DIL (35 versus 24 weeks).
      Musculoskeletal symptoms were prominent in DIL, while renal and pulmonary
      involvement was found in a significantly higher proportion of PTU-induced
      vasculitis. ANA, anti-DNA, and anti-histone were predominantly found in DIL,
      while p-ANCA was found in a similar proportion of patients in both groups. c-ANCA
      was detected only in patients with vasculitis. All patients with DIL completely
      recovered (most after stopping PTU), while about 50% of PTU-induced vasculitis
      needed steroids or immunosuppressive drugs, including cyclophosphamide and
      plasmapheresis. CONCLUSIONS: Most of the cases of PTU-induced autoimmune
      phenomena are due to vasculitis. Despite the common presence of p-ANCA in both
      DIL- and PTU-induced vasculitis, substantial differences in demographic,
      clinical, and outcome features of these entities allow an accurate diagnosis and
      consequent management.

PMID- 16887464
TI  - The effects of antifracture therapies on the components of bone strength:
      assessment of fracture risk today and in the future.
AB  - OBJECTIVE: To summarize the current knowledge regarding the impact of the most
      common antifracture medications on the various determinants of bone strength.
      METHODS: Relevant English-language articles acquired from Medline from 1966 to
      January 2005 were reviewed. Searches included the keywords bone AND 1 of the
      following: strength, remodeling, microcrack, structure, mineralization, collagen,
      organic, crystallinity, osteocyte, porosity, diameter, anisotropy, stress risers,
      or connectivity AND alendronate, estrogen, etidronate, hormone replacement
      therapy, parathyroid hormone, risedronate, OR teriparatide. Abstracts from
      relevant conference proceedings were also reviewed for pertinent information.
      RESULTS: Antiresorptive therapies increase bone strength through decreasing bone
      turnover. This lower bone turnover results in a higher mean mineralization and
      decreases the number of active resorption pits within bone at any given time.
      These resorption pits are speculated to be areas of focal weakness and a higher
      number of them would, if all other things were equal, result in greater
      fragility. Parathyroid hormone therapy increases the rate of bone remodeling,
      which introduces many resorption pits, but this source of strength loss is
      thought to be compensated by rapid increases in bone mass. CONCLUSIONS: Both the
      antiresorptives, particularly bisphosphonates, and the parathyroid hormone
      therapy increase bone strength; however, the changes that are elicited to achieve
      this differ significantly.

PMID- 16887465
TI  - Bone strength: the whole is greater than the sum of its parts.
AB  - OBJECTIVE: To summarize the current knowledge regarding the various determinants
      of bone strength. METHODS: Relevant English-language articles acquired from
      Medline from 1966 up to January 2005 were reviewed. Searches included the
      keywords bone AND 1 of the following: strength, remodeling, microcrack,
      structur*, mineralization, collagen, organic, crystallinity, osteocyte, porosity,
      diameter, anisotropy, stress risers, or connectivity. Abstracts from applicable
      conference proceedings were also reviewed for pertinent information. RESULTS:
      Bone strength is determined from both its material and its structural properties.
      Material properties such as its degree of mineralization, crystallinity, collagen
      characteristics, and osteocyte viability have substantial impacts on bone
      strength. Structural properties such as the diameter and thickness of the
      cortices, the porosity of the cortical shell, the connectivity and anisotropy of
      the trabecular network, the thickness of trabeculae, and the presence of
      trabecular stress risers and microcracks impact bone strength in diverse manners.
      Remodeling activity either directly or indirectly impacts all of these processes.
      CONCLUSIONS: Bone strength is dependent on numerous, interrelated factors.
      Remodeling activity has a direct impact on almost all of the components of bone
      strength and requires further investigation as to its impact on these factors in
      isolation and in unison.

PMID- 16887466
TI  - The role of mast cells in osteoporosis.
AB  - OBJECTIVES: The notion that mast cells and their secreted products play a
      potentially pathogenic role in osteoporosis bone loss is novel, but gaining
      substantial support. We reviewed the literature from 1950 to present to
      demonstrate an association between mast cells and bone turnover. The effect of
      primary increase in mast cells, deficiency in mast cells, and effect of mast
      cells during high remodeling states is discussed in this review. METHODS: A
      retrospective review of the literature was performed using Medline and MD Consult
      databases from 1957 to 2004. The keywords mast cell and osteoporosis revealed 200
      abstracts, limited to English and review articles. The references were further
      selected based on relevance to pathogenesis, research, and histamine's role in
      osteoporosis. RESULTS: Using the model of systemic mastocytosis, increased
      numbers of mast cells led to an acceleration of bone turnover. Activation
      mutations in tyrosine growth factor receptor, KIT, may be responsible for this
      occurrence. Mast cell deficiency demonstrates delayed osteoclastic recruitment
      and a delayed osteoblastic formation phase. Histamine deficiencies lead to a
      decrease in osteoclast number as reflected by tartrate-resistant acid phosphatase
      staining. Osteoblasts stimulated by parathyroid hormone synthesize abundant stem
      cell factor, which contributes to enhanced osteoclastogenesis. CONCLUSIONS: Mast
      cells appear to be relevant in the pathogenesis of bone turnover. Their
      deficiency has been associated with low remodeling states, while their excess is
      associated with accelerated bone loss. Even their byproducts are responsible for
      increased bone resorption. Inhibiting mast cells and/or their products many be a
      novel therapy for treating osteoporosis in the future.

PMID- 16887467
TI  - Prostaglandins in health and disease: an overview.
AB  - OBJECTIVES: Prostaglandins are a group of biologically active compounds that play
      major roles in human physiology in both health and disease. They function in many
      different ways and in all major organs. This article reviews the basic physiology
      of prostaglandins and their application to specific effects on these systems in
      normal and abnormal clinical states. The critical therapeutic implications of the
      use of nonsteroidal antiinflammatory drugs in altering organ homeostasis are also
      examined. METHODS: References were taken from Medline, Embase, and Index Medicus
      from 1966 to September 2005. A search was done with keywords, including
      prostaglandins, nonsteroidal antiinflammatory drugs, inflammation, arachidonic
      acid, Cox-1 (cyclooxygenase-1), and Cox-2 (cyclooxygenase-2). RESULTS: There was
      a close correlation and predictability between basic prostaglandin physiology and
      the anticipated effects of these compounds on the heart, lungs, kidneys,
      gastrointestinal tract, bones and joints, brain, and male and female reproductive
      systems. These effects are organ and tissue specific. Despite these findings,
      unexplained and sometimes paradoxical physiologic responses were identified. A
      prime example of this is the role of prostaglandins in bone metabolism
      demonstrating both stimulatory and inhibitory effects. In addition all NSAIDs
      have the potential to impair the normal physiologic effects of prostaglandins
      depending primarily on the specific organ and the clinical setting. CONCLUSIONS:
      Prostaglandins are regulatory compounds that play important roles in many
      physiologic processes in the human body. An understanding of the basic science of
      prostaglandins is valuable in anticipating the organ-specific biologic effects of
      these unique compounds in health and disease. However, at selected sites and
      under different physiologic conditions, unexplained and sometimes paradoxical
      effects are generated. Impairment of their regulatory functions can lead to
      significant short- or long-term organ dysfunction.

PMID- 16887468
TI  - Alternative decision analysis modeling in the economic evaluation of tumor
      necrosis factor inhibitors for rheumatoid arthritis.
AB  - OBJECTIVES: To provide a review of the studies that use decision models in the
      economic evaluation of tumor necrosis factor (TNF) inhibitors in rheumatoid
      arthritis (RA) and to address some important issues surrounding the choice of
      such modeling techniques in these economic evaluations. METHODS: A systematic
      literature search was conducted by 1 author from the literature published from
      January 1996 to March 2005 through Medline, Embase, and Cochrane library
      databases. RESULTS: The review yielded 29 studies that used decision models. Only
      10 studies used a decision model in the economic analysis of the TNF inhibitors
      and were included in the final review. Decision model types included the
      following in the review articles: decision tree (2), Markov model (7), and
      discrete event simulation (1). These models vary in complexity and their choice
      depends on the course of disease, the impact of treatment, and the available
      data. CONCLUSIONS: Based on the results derived from alternative modeling
      techniques, it is safe to say that all methods can provide useful information
      with regard to economic evaluations of TNF inhibitors. Even though different
      modeling techniques provide an appropriate representation of available data,
      their results should be interpreted contingent on the input data, assumptions,
      sensitivity analyses, and other alternative scenario analyses. RELEVANCE: The
      transparency in the models will encourage end users such as policymakers and
      prescribers to make informed judgments regarding the appropriateness of the
      methods and the validity of the results.

PMID- 16887469
TI  - Septic arthritis in patients with systemic lupus erythematosus: salmonella and
      nonsalmonella infections compared.
AB  - OBJECTIVES: To assess the clinical characteristics and outcome of systemic lupus
      erythematosus (SLE) with septic arthritis. METHODS: In this 20-year retrospective
      study, we reviewed the charts of SLE patients with septic arthritis confirmed by
      synovial fluid analysis and culture. To identify risk factors for septic
      arthritis, data of SLE patients with septic arthritis were compared with data of
      100 hospitalized SLE patients without septic arthritis. RESULTS: There were
      10,732 inpatient records of 3,127 SLE patients; 29 SLE patients had septic
      arthritis. Their ages ranged from 14 to 68 years (mean, 35.1 +/- 14.1 years). The
      mean SLE duration before septic arthritis onset was 30.6 months. All patients
      received corticosteroids; 93% had active disease (SLEDAI > or = 4). Compared with
      controls, avascular necrosis (AVN) of the femoral head was the most common
      predisposing articular disease (Odds ratio, 3.799;CI, 1.59 to 9.05). Of the 29
      patients, 17 (59%) had salmonella infections and 12 (41%) had other infections.
      Salmonella-infected patients were younger (28.7 +/- 10.4 years) than those with
      nonsalmonella infections (44.1 +/- 14.0 years; P = 0.002). The hip was the most
      commonly affected joint, especially in the salmonella group, followed by the
      knees and ankles. Salmonella-infected patients were more prone to oligo-articular
      septic arthritis. The overall mortality rate was 10%. CONCLUSIONS: Salmonella
      enteritidis B is the most common pathogen causing septic arthritis in younger SLE
      patients. Septic arthritis tended to be oligo-articular and involve the hip
      joint. AVN of the femoral head was the most common predisposing articular
      disease. Once septic arthritis is suspected, culture specimens should be
      collected and appropriate antibiotics given immediately.

PMID- 16887470
TI  - Standards for quality of rheumatologic care.

PMID- 16887471
TI  - Population pharmacokinetic modeling and Monte Carlo simulation of varying doses
      of intravenous metronidazole.
AB  - Population pharmacokinetic modeling and Monte Carlo simulation (MCS) are
      approaches used to determine probability of target attainment (PTA) of
      antimicrobial therapy. The objectives of this study were 1) to determine a
      population pharmacokinetic model (PPM) using metronidazole and hydroxy
      metronidazole concentrations from healthy subjects and critically ill patients,
      and 2) to determine the probability of attaining the pharmacodynamic target area
      under the plasma concentration (AUC)/MIC ratio >or=70 against 218 clinical
      isolates of Bacteroides fragilis using MCS. Eighteen healthy subjects were
      randomized to 3 dosages of intravenous metronidazole (500 mg every 8 h, 1000 mg
      day(-1), 1500 mg day(-1)) in an open-label 3-way crossover fashion. Serial blood
      samples were collected over 25.5 h on the 3rd day of each study period. An
      additional of 8 critically ill patients received intravenous metronidazole 500 mg
      every 8 h. Serial blood samples were collected over 8 h after the 2nd day of
      dosing. Plasma metronidazole and hydroxy-metronidazole concentrations were
      analyzed using a high-performance liquid chromatographic assay. The 834 plasma
      concentrations from 62 data sets were simultaneously modeled with Non-Parametric
      Adaptive Grid population modeling program. A 4-compartment model with a
      metabolite and zero-order infusion into the central compartment was used. The
      mean parameter vector and covariance matrix from PPM were inserted into the
      simulation module of ADAPT II. A 10,000-subject MCS was performed to determine
      the probability of PTA for a total drug AUC to MIC ratio >or=70 against 218
      isolates of B. fragilis (MIC range, 0.125-2.0 mg L(-1)). Mean parameter values
      were CL(non-OH), 3.08 L h(-1); Vc, 35.4 L; K(OH), 0.04 h(-1); CL(OH), 2.78 L h(
      1); and V(OH), 9.66 L. The regression values of the observed versus predicted
      concentrations (r2) of metronidazole and hydroxy-metronidazole were 0.972 and
      0.980, respectively. The PTA for metronidazole 1500 mg day(-1) or 500 mg every 8
      h (taken together) and 1000 mg day(-1) were 99.9% and 99.8%, respectively, over
      the reported MIC distribution range. For an MIC of 4 mg L(-1), the predicted PTA
      decreased to 80.0% and 28.5%, respectively. A PPM was determined by comodeling
      metronidazole and hydroxy-metronidazole concentrations from healthy subjects and
      critically ill patients. Based on this model, attainment of the target
      pharmacodynamic parameter (AUC/MIC ratio >or=70) against B. fragilis isolates is
      >99% when MICs are <2 mg L(-1), irrespective of the dosing interval of 24 h.

PMID- 16887472
TI  - Ethics of preimplantation genetic diagnosis for cancer.

PMID- 16887473
TI  - Keynote comment: challenges of teenage and young-adult oncology.

PMID- 16887474
TI  - Two approaches to cancer of the cardia.

PMID- 16887476
TI  - Dose and fractionation regimens for breast cancer.

PMID- 16887475
TI  - Is radiotherapy boost needed in young patients with ductal carcinoma-in-situ?

PMID- 16887477
TI  - Dose and fractionation regimens for breast cancer.

PMID- 16887480
TI  - Comprehensive side-effect profile of anastrozole and tamoxifen as adjuvant
      treatment for early-stage breast cancer: long-term safety analysis of the ATAC
      trial.
AB  - BACKGROUND: The Arimidex (anastrozole), Tamoxifen, Alone or in Combination (ATAC)
      trial was designed to compare the efficacy and safety of anastrozole with
      tamoxifen as adjuvant treatment for postmenopausal women with early-stage breast
      cancer. After an extended follow-up beyond the 5 years of treatment, we aimed to
      assess the safety, tolerability, and risk-benefit indices of these compounds.
      METHODS: We analysed postmenopausal women (mean age 64 years [SD 9]) with
      localised breast cancer randomly assigned to anastrozole (n=3125) or tamoxifen
      (n=3116). Efficacy measures, including death and risk-benefit indices, were
      analysed by intention to treat. Safety analyses were based on treatment first
      received (n=3092 for anastrozole and n=3094 tamoxifen). We calculated a risk
      benefit analysis using the two global indices for the Women's Health Initiative
      and for Disease-Free Survival and Serious Adverse Events. This study is
      registered as an International Standard Randomised Controlled Trial, number
      ISRCTN18233230. FINDINGS: At median follow-up of 68 months (range 1-93),
      treatment-related adverse events occurred significantly less often with
      anastrozole than with tamoxifen (1884 [61%] vs 2117 [68%]; p<0.0001), as did
      treatment-related serious adverse events (146 [5%] vs 277 [9%]; p<0.0001) and
      adverse events leading to withdrawal (344 [11%] vs 442 [14%]; p=0.0002). Patients
      given anastrozole had significantly fewer overall events for the Global Index of
      the Women's Health Initiative (744 [24%] vs 851 [27%]; hazard ratio 0.85 [95% CI
      0.77-0.94], p=0.001) and the Global Index of Disease-Free Survival and Serious
      Adverse Events (1453 [46%] vs 1594 [51%]; 0.88 [0.82-0.94]; p=0.0004).
      INTERPRETATION: Anastrozole is tolerated better than tamoxifen by postmenopausal
      women with early-stage breast cancer, and results in fewer serious adverse
      events. Furthermore, it has a more favourable overall risk-benefit profile and
      lower recurrence rate than tamoxifen.

PMID- 16887481
TI  - Left thoracoabdominal approach versus abdominal-transhiatal approach for gastric
      cancer of the cardia or subcardia: a randomised controlled trial.
AB  - BACKGROUND: Because of the inaccessibility of mediastinal nodal metastases, the
      left thoracoabdominal approach (LTA) has often been used to treat gastric cancer
      of the cardia or subcardia. In a randomised phase III study, we aimed to compare
      LTA with the abdominal-transhiatal approach (TH) in the treatment of these
      tumours. METHODS: Between July, 1995, and December, 2003, 167 patients were
      enrolled from 27 Japanese hospitals and randomly assigned to TH (n=82) or LTA
      (n=85). The primary endpoint was overall survival, and secondary endpoints were
      disease-free survival, postoperative morbidity and hospital mortality, and
      postoperative symptoms and change of respiratory function. The projected sample
      size was 302. After the first interim analysis, the predicted probability of LTA
      having a significantly better overall survival than TH at the final analysis was
      only 3.65%, and the trial was closed immediately. Analysis was by intention to
      treat. This study is registered with , number NCT00149266. FINDINGS: 5-year
      overall survival was 52.3% (95% CI 40.4-64.1) in the TH group and 37.9% (26.1
      49.6) in the LTA group. The hazard ratio of death for LTA compared with TH was
      1.36 (0.89-2.08, p=0.92). Three patients died in hospital after LTA but none
      after TH. Morbidity was worse after LTA than after TH. INTERPRETATION: Because
      LTA does not improve survival after TH and leads to increased morbidity in
      patients with cancer of the cardia or subcardia, LTA cannot be justified to treat
      these tumours.

PMID- 16887482
TI  - Boost radiotherapy in young women with ductal carcinoma in situ: a multicentre,
      retrospective study of the Rare Cancer Network.
AB  - BACKGROUND: Outcome data in young women with ductal carcinoma in situ (DCIS) are
      rare. The benefits of boost radiotherapy in this group are also unknown. We aimed
      to assess the effect of boost radiotherapy in young patients with DCIS. METHODS:
      We included 373 women from 18 institutions who met the following inclusion
      criteria: having tumour status Tis and nodal status (N)0, age 45 years or younger
      at diagnosis, and having had breast-conserving surgery. 57 (15%) patients had no
      radiotherapy after surgery, 166 (45%) had radiotherapy without boost (median dose
      50 Gy [range 40-60]), and 150 (40%) had radiotherapy with boost (60 Gy [53-76]).
      The primary outcome was local relapse-free survival. FINDINGS: Median follow-up
      was 72 months (range 1-281). 55 (15%) patients had local relapse. Local relapse
      free survival at 10 years was 46% (95% CI 24-67) for patients given no
      radiotherapy, 72% (61-83) for those given radiotherapy without boost, and 86% (78
      93) for those given radiotherapy and boost (difference between all three groups,
      p<0.0001). Age, margin status, and radiotherapy dose were significant predictors
      of local relapse-free survival. Compared with patients who had no radiotherapy,
      those who had radiotherapy had a decreased risk of local relapse (without boost,
      hazard ratio 0.33 [95% CI 0.16-0.71], p=0.004; with boost, 0.15 [0.06-0.36],
      p<0.0001). INTERPRETATION: In the absence of randomised trials, boost
      radiotherapy should be considered in addition to surgery for breast-conserving
      treatment for DCIS.

PMID- 16887483
TI  - Emerging use of nanoparticles in diagnosis and treatment of breast cancer.
AB  - The biological application of nanoparticles is a rapidly developing area of
      nanotechnology that raises new possibilities in the diagnosis and treatment of
      human cancers. In cancer diagnostics, fluorescent nanoparticles can be used for
      multiplex simultaneous profiling of tumour biomarkers and for detection of
      multiple genes and matrix RNA with fluorescent in-situ hybridisation. In breast
      cancer, three crucial biomarkers can be detected and accurately quantified in
      single tumour sections by use of nanoparticles conjugated to antibodies. In the
      near future, the use of conjugated nanoparticles will allow at least ten cancer
      related proteins to be detected on tiny tumour sections, providing a new method
      of analysing the proteome of an individual tumour. Supermagnetic nanoparticles
      have exciting possibilities as contrast agents for cancer detection in vivo, and
      for monitoring the response to treatment. Several chemotherapy agents are
      available as nanoparticle formulations, and have at least equivalent efficacy and
      fewer toxic effects compared with conventional formulations. Ultimately, the use
      of nanoparticles will allow simultaneous tumour targeting and drug delivery in a
      unique manner. In this review, we give an overview of the use of clinically
      applicable nanoparticles in oncology, with particular focus on the diagnosis and
      treatment of breast cancer.

PMID- 16887484
TI  - People's perceptions of cancer survivability: implications for oncologists.
AB  - Individuals typically overestimate survival for lung cancer and underestimate it
      for melanoma. However, reporting of results generally masks the extent of
      disagreement between people on survival rates. Most methods used to question
      individuals are of little use and are not comparable across studies. The topic of
      people's perceptions of survival for various cancers is under-researched. A
      clearer definition is needed of survivability, as is a standard way to measure it
      and then present the information. We have undertaken a review of studies
      reporting public perceptions of cancer survival rates and compared the results,
      where possible, with actual survival rates. We also investigate some potential
      implications of people's underestimation or overestimation of survival for
      screening and prevention behaviours and delineate implications for oncologists.

PMID- 16887485
TI  - Particle therapy and treatment of cancer.
AB  - The desire of radiation oncologists and medical physicists to maximise the
      radiation dose to the tumour while minimising that to healthy tissues has led to
      attempts to improve the dose distributions and biological effects achievable with
      photons and electrons. Protons, neutrons, pions, boron-neutron capture therapy,
      and charged-nuclei therapy (with argon, carbon, helium [alpha particles], neon,
      nitrogen, and silicon) have been assessed for their physical, biological, and
      clinical effects. In the 90 years since protons and neutrons were discovered,
      investigations of particle therapy for cancer have helped to elucidate many
      fundamental radiobiological ideas, such as linear energy transfer, relative
      biological effectiveness, oxygen effect, and oxygen enhancement. Particle therapy
      has contributed to our understanding of medical ethics when neutron therapy
      became intertwined with the debate over standards of informed consent in
      radiation experiments in humans during the cold war era. Particle teletherapy and
      brachytherapy continue to show promise in some clinical situations. In the
      future, the insights of molecular biology might clarify the ideal particles for
      clinical situations.

PMID- 16887486
TI  - Sentinel lymph nodes in breast cancer after 10 years: rethinking basic
      principles.
AB  - New techniques and treatments in medicine occasionally take on a life of their
      own. Sometimes, an idea's use is inherently obvious from the outset, sometimes
      not, in which case it becomes technology in search of an application.
      Identification of sentinel lymph nodes in breast cancer is a combination of these
      two options: to some extent the technique has been overused and its results
      overinterpreted. 10 years after the procedure's introduction and general
      acceptance, a few issues still deserve further discussion despite much published
      work on this topic. Use of sentinel-lymph-node identification has been extended
      to other organ systems, yet not all the lessons learned in the breast might apply
      to other sites. Review of the theory behind the technique and breast cancer
      experience to date is important. Many of the published controversies about
      sentinel lymph nodes in breast cancer can be resolved by consideration of the
      basic ideas underlying the procedure, which is the aim of this Essay.

PMID- 16887487
TI  - Rituximab plus CHOP for treatment of diffuse large B-cell lymphoma during second
      trimester of pregnancy.

PMID- 16887488
TI  - Antiangiogenic therapy in metastatic prostate carcinoma complicated by cutaneous
      lupus erythematodes.

PMID- 16887489
TI  - Combined three-dimensional microscopic visualisation of tumour-invasion front of
      cervical carcinoma.

PMID- 16887490
TI  - Translating translational research.

PMID- 16887491
TI  - Clinical and translational science awards: a framework for a national research
      agenda.

PMID- 16887492
TI  - Molecular diagnosis of alpha-thalassemia by combining real-time PCR with SYBR
      Green1 and dissociation curve analysis.
AB  - The aim of the study was to set up an automatic molecular diagnostic method for
      deletional alpha-thalassemia without gel electrophoresis and TaqMan probe. Four
      real-time polymerase chain reactions (PCRs) with SYBR Green1 and ABI7000 (SYBR
      PCR) followed by dissociation curve (DC) analysis were used to detect the -
      (SEA), - alpha(3.7), -alpha(4.2), and non-deletion-type alleles (alpha alpha or
      alpha(T)alpha), respectively. Positive results of the SYBR-PCRs were defined by
      the special shapes of the dissociation curves and the peak height at specific Tm
      for each predetermined PCR at a specific Tm for each PCR amplicon > or = cutoff
      values. Molecular diagnosis of alpha-thalassemia was determined by combining all
      four SYBR-PCR results. The specific Tms for the SYBR-PCR1-4, which was used to
      detect the --(SEA), - alpha(3.7), -alpha(4.2), and non-deletion-type alleles were
      82.5 +/- 1 degrees Celsius, 82.8 +/- 1 degrees Celsius, 81.5 +/- 1 degrees
      Celsius, and 83.0 +/- 1 degrees Celsius, respectively. The cutoff values of the
      specific peaks for the positive amplificons were 40, 20, 10, and 70. The C(T) VS
      log copies of a recombinant plasmid DNA showed a good linear relationship between
      10(5) approximately 10(0). Sensitivity of the SYBR-PCR-based method was at least
      16 times higher than the multiplex PCR (mPCR)/gel electrophoresis method.
      Diagnostic outcomes of the 120 alpha-thalassemia cases by using the SYBR-PCR and
      DC analysis techniques were shown to be the same as that by using the mPCR/gel
      electrophoresis methods. The SYBR-PCR combined with the DC analysis technique is
      an alternative assay for the routine molecular diagnosis of alpha-thalassemia.

PMID- 16887493
TI  - Point-of-care Helicobacter pylori urine antibody detection in a multi-ethnic
      adult population in the United States.
AB  - A need exists for accurate point-of-care tests for diagnosis of Helicobacter
      pylori (H. pylori) infection to evaluate a rapid urine-H. pylori antibody test
      device for detection of H. pylori infection in a point-of-care setting in the
      United States. A multi-center study in a multi-ethnic population compared the
      RAPIRUN urine antibody test with the (13)C-urea breath test (C-UBT) and a
      traditional serologic test, the high-molecular-weight cell-associated protein
      enzyme immunoassay (HM-CAP EIA). The primary comparator was with "definite
      positive" and "definite negative" patients defined as a concordance of combined
      results of the UBT and the HM-CAP IgG EIA. Overall, 188 eligible patients were
      enrolled (61 men, age range: 18-73 years, including 84 Hispanics, 73 Asian
      Pacific Americans, 22 Black African-Americans, 6 non-Hispanic Caucasians, and 3
      of "other" ethnicity). Compared with "definite positive" and "definite negative"
      results, the sensitivity and specificity of the urine antibody test were 0.9 and
      1.0, respectively. The urine antibody test proved suitable for point-of-care
      rapid diagnosis of anti-H. pylori antibodies indicative of active or past H.
      pylori infection.

PMID- 16887494
TI  - Lactadherin binding and phosphatidylserine expression on cell surface-comparison
      with annexin A5.
AB  - BACKGROUND: Transbilayer movement of anionic phospholipids from the inner to the
      outer leaflet of the plasma membrane occurs during platelet activation, red cell
      senescence, and apoptosis. The anionic phospholipid-binding protein, annexin A5,
      has been used to detect the presence of phosphatidylserine on the outer leaflet
      of the cell membrane. Lactadherin, a glycoprotein secreted by macrophages, binds
      to phosphatidylserine on apoptotic cells and promote their clearance by
      macrophages. METHODS: The authors isolated and labeled lactadherin and annexin A5
      with FITC and compared their ability to detect phosphatidylserine expression by
      flow cytometry. RESULTS: FITC-lactadherin induced greater shift in the histogram
      and a higher mean fluorescence intensity than FITC-annexin A5 when platelets were
      activated with thrombin (0.1 unit/mL) or Ca(2+) ionophore A23187 (1 microM).
      Similarly, lactadherin was more sensitive in detecting phosphatidylserine in red
      cells induced to express phosphatidylserine. Also, in HL 60 cells undergoing
      apoptosis, lactadherin detected phosphatidylserine expression earlier than
      annexin A5. In patients with disseminated intravascular coagulation, lactadherin
      detected phosphatidylserine-expressing platelets in most patients, whereas under
      similar conditions, FITC-annexin A5 could not. CONCLUSIONS: The authors' studies
      show that FITC-lactadherin is a better probe than annexin A5 in detecting
      phosphatidylserine-expressing activated platelets, red cells, and apoptotic
      cells.

PMID- 16887495
TI  - The cardiovascular risk marker asymmetrical dimethylarginine is not affected by
      venous thromboembolism.
AB  - Asymmetrical dimethylarginine (ADMA) is an endogenous inhibitor of endothelial
      nitric oxide synthase, causes vasoconstriction, impairs cardiac function, and may
      predict cardiovascular risk. The prognostic value of plasma ADMA concentrations
      in acute vascular situations may be confounded by concomitant factors such as
      clot formation. In an effort to address the effect of hemostatic system
      activation, the authors have measured plasma concentrations of ADMA, its
      stereoisomer symmetrical dimethylarginine (SDMA), and L-arginine in 74 patients
      with suspected deep vein thrombosis (DVT). DVT was confirmed by sonography or
      venography in 39 subjects. There was no difference of L-arginine, ADMA, or SDMA
      (all P > 0.05) between subjects with or without DVT. ADMA correlated with SDMA, L
      arginine, and plasma creatinine (all P < 0.05) but not with age, body mass index,
      D-dimer, thrombus extension, or history of symptoms. Venous thrombembolism does
      not influence circulating ADMA concentrations. The lack of association between
      ADMA and DVT argues against a contribution of endogenous NO synthase inhibition
      in hemostatic systemic activation.

PMID- 16887496
TI  - Reduced cardiac functional reserve in apolipoprotein E knockout mice.
AB  - Several years ago, the authors reported that aortic flow velocity under resting
      conditions was significantly higher in apolipoprotein E knockout (apoE-KO) mice
      than in age-matched C57Black/6J wildtype (WT) controls. The goal of this study
      was to examine whether the cardiac functional reserve is impacted in response to
      a pharmacological stress agent in apoE-KO mice. Cardiac function was measured
      noninvasively by the Doppler ultrasound method at baseline and at 1 min, 5 min,
      10 min, and 20 min after intraperitoneal injection of dobutamine at the doses of
      1 microg/g, 3 microg/g, or 10 microg/g in 16-month-old male apoE-KO (n = 9) and
      WT (n = 10) mice under light anesthesia with 1.5% isoflurane via inhalation. The
      baseline peak and mean aortic flow velocities were 39% to 48% higher, and left
      ventricular contractility measured by peak acceleration rate of aortic flow
      velocity was 24% higher in apoE-KO compared with WT mice (P < 0.01). Dobutamine
      stress dose-dependently increased cardiac function, which, however, was
      significantly smaller with a right shift of the dose-response curve in apoE-KO
      mice compared with WT controls. The hypotensive response to dobutamine was not
      significantly different between the 2 groups. Thus, despite an elevated resting
      aortic flow velocity and left ventricular contractility, cardiac functional
      reserve in response to dobutamine stress was significantly reduced in apoE-KO
      mice, which could be the consequence of coronary atherosclerosis and endothelial
      dysfunction that limits blood supply to the heart.

PMID- 16887498
TI  - Reduced podocyte expression of alpha3beta1 integrins and podocyte depletion in
      patients with primary focal segmental glomerulosclerosis and chronic PAN-treated
      rats.

PMID- 16887500
TI  - Anaerobic infections in humans: an overview.

PMID- 16887501
TI  - Pasteur, oxygen and the anaerobes revisited.
AB  - As a biochemist, Louis Pasteur focused on fermentation, demonstrating that it was
      a vital process. In 1860, he discovered anaerobic life and the strict anaerobes,
      particularly those responsible for butyric fermentation. Then, in spite of his
      lack of medical background, Pasteur turned to investigating the role of bacteria
      in human and animal diseases. In 1877, Pasteur and Joubert described for the
      first time a pathogenic anaerobe, the 'septic vibrio' (now Clostridium septicum).
      Not only was the bacterium cultivated, but the disease symptoms described and the
      disease experimentally reproduced. Pasteur also described what are now known as
      mixed anaerobic infections. A historical review of Pasteur's work is made in the
      light of our present knowledge of this field.

PMID- 16887497
TI  - Effects of chenodeoxycholic acid and deoxycholic acid on cholesterol absorption
      and metabolism in humans.
AB  - Quantitative and qualitative differences in intralumenal bile acids may affect
      cholesterol absorption and metabolism. To test this hypothesis, 2 cross-over
      outpatient studies were conducted in adults with apo-A IV 1/1 or apo-E 3/3
      genotypes. Study 1 included 11 subjects 24 to 37 years of age, taking 15
      mg/kg/day chenodeoxycholic acid (CDCA) or no bile acid for 20 days while being
      fed a controlled diet. Study 2 included 9 adults 25 to 38 years of age, taking 15
      mg/kg/day deoxycholic acid (DCA) or no bile acid, following the same experimental
      design and procedures as study 1. CDCA had no effect on plasma lipid
      concentrations, whereas DCA decreased (P < 0.05) plasma high-density lipoprotein
      (HDL)-cholesterol and tended to decrease (P = 0.15) low-density lipoprotein (LDL)
      cholesterol. CDCA treatment enriched (P < 0.0001) bile with CDCA and increased
      cholesterol concentration in micelles, whereas meal-stimulated bile acid
      concentrations were decreased. DCA treatment enriched (P < 0.0001) bile with DCA
      and tended to increase intralumenal cholesterol solubilized in micelles (P =
      0.06). No changes were found in cholesterol absorption, free cholesterol
      fractional synthetic rate (FSR), or 3-hydroxy-3 methylglutaryl (HMG) CoA
      reductase and LDL receptor messenger ribonucleic acid (mRNA) levels after CDCA
      treatment. DCA supplementation tended to decrease cholesterol absorption and
      reciprocally increase FSR and HMG CoA reductase and LDL receptor mRNA levels.
      Results of these 2 studies suggest that the solubilization of cholesterol in the
      intestinal micelles is not a rate-limiting step for its absorption.

PMID- 16887502
TI  - Isolation of Propionibacterium acnes from central nervous system infections.
AB  - Propionibacterium acnes is a common skin colonizer and its involvement in central
      nervous system (CNS) infections may be related with previous neurosurgical
      procedures. P. acnes was isolated in pure or mixed cultures from ten patients
      with CNS infections during a 5-year period. The clinical presentation, treatment
      and outcome were retrospectively reviewed. Nine out of 11 patients had CNS
      infections after a neurosurgical procedure. The clinical presentation was: brain
      abscess (five patients), subdural or epidural empyema (four patients) and shunt
      meningitis (one patient). Three patients had also secondary meningitis. All
      patients received antibiotic therapy and all abscesses and empyemas were drained.
      The patient with shunt meningitis cured without catheter removal. Only one
      patient with a brain abscess by P. acnes died, but several months thereafter and
      as a consequence of a Gram-negative superinfection. P. acnes is a pathogen for
      the CNS and infections must be surgically managed under adequate antibiotic
      treatment.

PMID- 16887503
TI  - Preliminary evidence of endotoxic activity of Bilophila wadsworthia.
AB  - In this study we describe two properties of the Gram-negative bacterium Bilophila
      wadsworthia, namely the ability to clot Limulus lysate and the capacity to induce
      the production of tissue factor-like procoagulant activity by human mononuclear
      cells in vitro. Although exhibited at a lower degree when compared with those of
      typical Gram-negative bacteria or Gram-negative endotoxin those activities may
      account in part for Bilophila's pathogenicity. The capacity indeed to induce
      fibrin formation through the interaction with mononuclear cells suggests one
      mechanism by which the microorganism might cause abscess formation in the host.
      Moreover, since this activity is dependent on the number of Bilophila interacting
      with mononuclear cells, we hypothesize that this biological activity is closely
      influenced by growth environment.

PMID- 16887504
TI  - Carbohydrate utilization patterns and substrate preferences in Bacteroides
      thetaiotaomicron.
AB  - Specific growth rates of Bacteroides thetaiotaomicron NCTC 10582 with either
      glucose, arabinose, mannose, galactose or xylose as sole carbon sources were
      0.42/h, 0.10/h, 0.38/h, 0.38/h and 0.16/h respectively, suggesting that hexose
      metabolism was energetically more efficient than pentose fermentation in this
      bacterium. Batch culture experiments to determine whether carbohydrate
      utilization was controlled by substrate-induced regulatory mechanisms
      demonstrated that mannose inhibited uptake of glucose, galactose and arabinose,
      but had less effect on xylose. Arabinose and xylose were preferentially utilized
      at high dilution rates (D > 0.26/h) in carbon-limited continuous cultures grown
      on mixtures of arabinose, xylose, galactose and glucose. When mannose was also
      present, xylose was co-assimilated at all dilution rates. Under nitrogen-limited
      conditions, however, mannose repressed uptake of all sugars, showing that its
      effect on xylose utilization was strongly concentration dependent. Studies with
      individual D-ZU-14C]-labelled substrates showed that transport systems for
      glucose, galactose, xylose and mannose were inducible. Measurements to determine
      incorporation of these sugars into trichloroacetic acid-precipitable material
      indicated that glucose and mannose were the principal precursor monosaccharides.
      Xylose was only incorporated into intracellular macromolecules when it served as
      growth substrate. Phosphoenolpyruvate:phosphotransferase systems were not
      detected in preliminary experiments to elucidate the mechanisms of sugar uptake,
      and studies with inhibitors of carbohydrate transport showed no consistent
      pattern of inhibition with glucose, galactose, xylose and mannose. These results
      indicate the existence of a variety of different systems involved in sugar
      transport in B. thetaiotaomicron.

PMID- 16887505
TI  - Evidence for H2 and formate formation during syntrophic butyrate and propionate
      degradation.
AB  - Both H2 and formate were formed during butyrate oxidation by Syntrophospora
      bryantii with pentenoate as electron acceptor and during propionate oxidation by
      a mesophilic propionate oxidizing bacterium (MPOB) with fumarate as electron
      acceptor. H2 and formate levels were affected by the bicarbonate concentration. S
      bryantii and MPOB were also able to interconvert formate and H2+ HCO3-; the
      apparent K(M) values for formate were of 2.9 mM and 1.8 mM, respectively. The
      conversion of H2+ HCO3- to formate was detected only when the H2 partial pressure
      was above 80 kPa. This interconversion seems to be rather unimportant under
      conditions prevailing during syntrophic propionate and butyrate oxidation.

PMID- 16887506
TI  - Carbohydrate fermentation by three species of polycentric ruminal fungi from
      cattle and water buffalo in tropical Australia.
AB  - Fructose, glucose and xylose were the only monosaccharides to be fermented by the
      polycentric fungi, Orpinomyces joyonii (three cattle isolates) and O.
      intercalaris (two cattle isolates) and Anaeromyces spp. (four cattle isolates and
      two water buffalo isolates). Both Orpinomyces spp. utilised a similar range of
      oligosaccharides and polysaccharides by fermenting cellobiose, gentiobiose,
      lactose, maltose, sucrose, cellulose, glycogen, starch and xylan. In contrast,
      there was considerable variation in carbohydrate fermentation amongst Anaeromyces
      spp., with only cellobiose, gentiobiose and cellulose being fermented by all
      strains. Formate, acetate and ethanol were the major fermentation end-products
      formed from glucose by all polycentric fungi. In addition, Anaeromyces spp.
      produced considerable amounts of lactate, although only small amounts were formed
      by Orpinomyces spp. This difference was explained by the low specific activity
      for lactate dehydrogenase in Orpinomyces spp. Several Anaeromyces spp. also
      produced malate as a significant end-product of glucose fermentation.
      Fermentation of specifically-labelled Z14C]glucose molecules by polycentric fungi
      showed that hexose was catabolised by both polycentric and monocentric fungi via
      the glycolysis pathway with end-products being derived from the following carbon
      atoms: lactate and malate (C1-C3; C4-C6), acetate and ethanol (C1-C2; C5-C6), CO2
      and formate (C3; C4). The results were compared to those obtained for monocentric
      and polycentric fungi isolated from temperate climate ruminants.

PMID- 16887507
TI  - Catalytic site targeted mutagenesis of the alpha-gingivain gene of Porphyromonas
      gingivalis using Tn-4351 to generate isogenic mutants.
AB  - The extracellular proteinases of the anaerobe Porphyromonas gingivalis, are
      implicated in the destruction of host defence mechanisms in periodontitis. We
      have previously purified one of these enzymes, alpha-gingivain, and established
      that it belongs to the cysteine proteinase family of enzymes. In the present
      study, transposon Tn4351 was used to alter the open reading frame encoding a
      region that includes the catalytic site of alpha-gingivain by targeted
      mutagenesis. Escherichia coli HB101 which harbours R751 was used to introduce the
      transposon into P. gingivalis ATCC 33277 by conjugal transfer. E. coli was
      transformed using the altered plasmid with a Cla I site insertion of a sequence
      common to the catalytic site histidine or cysteine of many cysteine proteinases.
      The frequency of the transconjugation was 4.5 x 10(5) while the recipient viable
      counts comprised 60% of the original P. gingivalis. The result of this targeted
      mutagenesis was inactivation of gingivains such that some colonies on skimmed
      milk agar plates showed no clear surrounding zones of hydrolysis and their normal
      catalytic activity towards L-BAPNA was destroyed.

PMID- 16887508
TI  - Isolation and preliminary characterization of a soluble nitrate reductase from
      the sulfate reducing organism Desulfovibrio desulfuricans ATCC 27774.
AB  - Desulfovibrio desulfuricans ATCC 27774 is a sulfate reducer that can adapt to
      nitrate respiration, inducing the enzymes required to utilize this alternative
      metabolic pathway. Nitrite reductase from this organism has been previously
      isolated and characterized, but no information was available on the enzyme
      involved in the reduction of nitrate. This is the first report of purification to
      homogeneity of a nitrate reductase from a sulfate reducing organism, thus
      completing the enzymatic system required to convert nitrate (through nitrite) to
      ammonia. D. desulfuricans nitrate reductase is a monomeric (circa 70 kDa)
      periplasmic enzyme with a specific activity of 5.4 K(m) for nitrate was estimated
      to be 20 microM. EPR signals due to one [4Fe-4S] cluster and Mo(V) were
      identified in dithionite reduced samples and in the presence of nitrate.

PMID- 16887509
TI  - Hydrogenase I of Clostridium pasteurianum functions as a novel selenite
      reductase.
AB  - Clostridium pasteurianum's hydrogenase I, an important constitutive metabolic
      enzyme, has been shown to function as a 'novel selenite reductase'. Selenite
      reductase activity was found to co-purify with hydrogenase I activity; the fold
      purification and specific activities for these two activities paralleled each
      other throughout the purification steps. The highly purified hydrogenase I
      apparent K(m) for the selenite substrate was 0.2 mM. The stoichiometry for the
      enzymatic reduction of SeO3(2-) to Se(0) via H2 oxidation, was determined to be
      2.3:1 (H2:Se(0)), very close to the theoretical ratio of 2:1 for this reduction
      reaction. Known electron carriers required for hydrogenase I activity were also
      found to couple its selenite reductase activity, the most efficient one being
      ferredoxin. The purified hydrogenase I not only reduced selenite but also
      tellurite, and its selenite activity was completely inhibited by O2 and CuSO4,
      potent inhibitors of hydrogenase I activity.

PMID- 16887510
TI  - Antimicrobial resistance in anaerobic bacteria: current situation.

PMID- 16887511
TI  - Reduction of metronidazole by hydrogenase from clostridia.

PMID- 16887512
TI  - Resistance of veillonella to hydrosoluble pristinamycins: a possible outer
      membrane barrier effect.
AB  - An in vitro study on 25 Veillonella strains showed a consistent clindamycin
      susceptibility with resistance to erythromycin and to the hydrosoluble
      pristinamycins, quinupristin and dalfopristin and its 30:70 combination, the
      synergistin RP59500. Double erythromycin-clindamycin disk tests did not show any
      inducible resistance pattern. The addition of 10 or 50 mug/mL of polymyxin B
      nonapeptide, an outer membrane permeabilizing agent, consistently reduced
      quinupristin and dalfopristin MICs in most strains. This result suggests that the
      Veillonella outer membrane may act as a permeability barrier to these
      antibiotics, as in the case of other Gram-negative bacteria.

PMID- 16887513
TI  - Comparison of arbitrarily primed polymerase chain reaction and ribotyping for
      subtyping Actinobacillus actinomycetemcomitans.
AB  - This study investigated the compatibility of arbitrarily primed polymerase chain
      reaction (AP-PCR) and ribotyping in the characterization of Actinobacillus
      actinomycetemcomitans , a major pathogen in the mixed anaerobic microflora of
      human periodontitis. AP-PCR was performed directly on lysed bacterial colonies
      using a random-sequence 10-base oligonucleotide primer. Ribotyping was carried
      out by using purified bacterial chromosomal DNA digested with BglI. DNA fragments
      were separated electrophoretically, blotted onto a nylon membrane and hybridized
      with the plasmid pKK3535 containing the rRNA operon of Escherichia coli. The two
      genetic methods were evaluated on isolates from single individuals and from
      family members. Twelve AP-PCR types and 47 ribotypes were distinguished among 76
      A. actinomycetemcomitans isolates of different serotypes. AP-PCR typing and
      ribotyping gave compatible results in 18 of 20 comparisons. Although AP-PCR
      detected less genetic heterogeneity in A. actinomycetemcomitans than ribotyping,
      the rapid and relatively simple AP-PCR technique seems to be sufficiently
      discriminative to be used in large scale epidemiological studies which preclude
      the application of the more laborious ribotyping technique.

PMID- 16887514
TI  - Arabinogalactan utilization in continuous cultures of Bifidobacterium longum:
      effect of co-culture with Bacteroides thetaiotaomicron.
AB  - Studies showed that the plant cell wall polysaccharide arabinogalactan supported
      growth of Bifidobacterium longum in batch culture. Galactose was also utilized,
      but not arabinose, the other major constituent sugar of the polymer. Enzymes
      required for hydrolysis of arabinogalactan ('arabinogalactanase', alpha
      arabinopyranosidase, beta-galactosidase) were inducible and cell-associated in B.
      longum, and their expression was repressed by glucose. Considerable amounts of
      alpha-arabinopyranosidase and beta-galactosidase were synthesized during growth
      on arabinogalactan, but only low levels of arabinogalactanase were detected. B.
      longum only grew on arabinogalactan in continuous culture under putative carbon
      excess conditions. In C-limited chemostats, the bifidobacterium could not
      establish unless Bacteroides thetaiotaomicron was present in co-culture. The
      relationship between the two organisms was not simply commensal; at low specific
      growth rates, bacteroides cell population densities were approximately 30% lower
      than those recorded in axenic culture, indicating the existence of competitive
      interactions with the bifidobacterium. In contrast, at high specific growth
      rates, a mutualistic association was observed, in that Bact. thetaiotaomicron was
      maintained in the chemostats at high dilution rates if bifidobacteria were also
      present. Measurements of residual carbohydrate in spent culture fluid from C
      limited chemostats indicated that a large part of the arabinogalactan molecule
      could not be broken down by either B. longum or Bact. thetaiotaomicron alone, or
      in co-culture. Formate and acetate were the major fermentation products of B.
      longum cultured in the presence of high concentrations of arabinogalactan,
      confirming that these bacteria were growing under energy-limited conditions.

PMID- 16887515
TI  - Effect of the feed frequency on the performance of anaerobic filters.
AB  - Anaerobic filter technology is suitable for the treatment of biodegradable
      organic wastes: for example, wastewaters from food industries. These wastewaters
      are not produced in a continuous mode since they are of seasonal nature and hence
      their production varies considerably during the year. In this work, a study of
      the performance of anaerobic filters with changing feeding systems was
      undertaken. A comparison was made between continuous feeding and different
      semicontinuous modes of feeding (in which the overall volume to be added into the
      reactors was divided into several doses and each of them were added at a constant
      interval of time). Filter performance was characterized by determining the
      different operational variables: depurative efficiency, methane production,
      biogas composition and volatile acids. From the obtained results, we conclude
      that the optimum feed frequency range is 24 doses/day or more. The continuously
      fed system has both greater stability and degradation efficiency.

PMID- 16887516
TI  - Antibacterial activity of the metabolic by-products of a Veillonella species and
      Bacteroides fragilis.
AB  - A Veillonella species and Bacteroides fragilis were isolated from the cecal
      contents of adult chickens. When growth on an agar medium supplemented with 0.4%
      glucose and adjusted to pH 6.5, mixed cultures containing Veillonella and B.
      fragilis inhibited the growth of Salmonella typhimurium; Salmonella enteritidis,
      Escherichia coli 0157:H7 and Pseudomonas aeruginosa. Decreasing the glucose
      concentration of the agar decreased the inhibitory activity of the mixed culture.
      Mixed cultures grown on agar media supplemented with 0.5% glucose and adjusted to
      pH 6.5, 7.0 or 7.5 also inhibited the growth of S. typhimurium, S. enteritidis,
      E. coli 0157:H7 and P. aeruginosa. However, increasing the pH of the agar
      decreased the inhibitory activity of the mixed culture. Pure cultures of
      Veillonella or B. fragilis did not inhibit the growth of S. typhimurium, S.
      enteritidis, E. coli 0157:H7 or P. aeruginosa on any of the agar supplemented
      with different concentrations of glucose or on any of the agar adjusted to
      different pH levels. The inhibitory activity of the mixed culture was correlated
      with the concentration of volatile fatty acids that were formed as B. fragilis
      metabolized glucose to produce succinate and acetate and as the succinate
      produced by B. fragilis was decarboxylated by Veillonella to produce propionate.

PMID- 16887517
TI  - Outer membrane-associated deoxyribonuclease activity of Porphyromonas gingivalis.
AB  - Extracellular outer membrane vesicles which are produced by Gram-negative
      bacteria may enclose deoxyribonucleic acid (DNA). While characterizing vesicles
      of Porphyromonas gingivalis, it was found that they do not contain detectable
      amount of DNA. It was also shown that the presence of deoxyribonuclease activity
      on whole cells and vesicles can degrade plasmidic and linear DNA.
      Deoxyribonuclease activity was also demonstrated in several other Gram-negative
      oral bacterial species. The nuclease activity of P. gingivalis was further
      characterized. When deoxyribonuclease activity was analyzed by zymography, only
      one active band was detected under the conditions tested. This nuclease enzyme
      showed a molecular weight of approximately 50 kDa. The activity was inhibited by
      5 mM ZnCl2 or 100 mM EDTA whereas Mg2+ or Ca2+ ions were not required for
      activity. Activity was totally destroyed by treatment at 70 degrees C for 15 min.
      Although the enzyme may participate in virulence or provide nucleic acid
      precursors for bacterial growth, its exact role is still unknown.

PMID- 16887518
TI  - Sphingolipid composition in Bacteroides species.
AB  - Sphingolipid profiles of strains from species of genus Bacteroides, and
      representative strains from Prevotella and Porphyromonas, were analyzed by thin
      layer chromatography and infrared spectrophotometry. Two major types of
      phosphosphingolipid, ceramide phosphorylethanolamine and ceramide
      phosphorylglycerol, were detected in B. fragilis, B. ovatus, B. uniformis, B.
      caccae, B. eggerthii, B. thetaiotaomicron, and B. stercoris, but not in B.
      merdae, B. distasonis, and B. vulgatus. Strains from the genera Prevotella and
      Porphyromonas also contained these two sphingolipids. These sphingolipid profiles
      were conserved within the species tested, and may be useful for differentiation
      and recognition of relationships within the genera Bacteroides, Prevotella and
      Porphyromonas.

PMID- 16887520
TI  - Conjugative transposons: the force behind the spread of antibiotic resistance
      genes among Bacteroides clinical isolates.

PMID- 16887519
TI  - Society for Anaerobic Microbiology.

PMID- 16887521
TI  - Variability in survival of Pectinatus cerevisiiphilus, strictly anaerobic
      bacteria, under different oxygen conditions.
AB  - Survival of Pectinatus cerevisiiphilus DSM 20466 in pure culture at variable
      temperatures under different oxygen concentrations was measured. Survival of P.
      cerevisiiphilus in co-culture with Saccharomyces cerevisiae under both saturated
      oxygen and brewing conditions was also studied. The survival of strictly
      anaerobic bacteria to oxygen seems to follow the classical laws of heat
      resistance. The D(oxy) values of P. cerevisiiphilus , calculated as a function of
      oxygen level, shows that the oxygen level is important for the survival duration
      of the bacteria. The temperature greatly influences the oxygen resistance of P.
      cerevisiiphilus, which increases when the temperature decreases. P.
      cerevisiiphilus resists better in co-culture than in pure culture under saturated
      oxygen conditions. Therefore, the oxygenation of the wort does not totally
      eliminate the risk of beer contamination by this bacterium. Under brewing
      conditions in co-culture at 8 degrees C, P. cerevisiiphilus grows slowly to reach
      a final cell concentration up to 10(6) cells/mL in beer, which is undrinkable.
      Pectinatus is a strictly anaerobic bacterium; however, it is resistant under
      certain oxygen conditions of incubation. This resistance is considerably higher
      in the presence of Saccharomyces cerevisiae .

PMID- 16887522
TI  - A rapid test for the presumptive identification of Clostridium perfringens.
AB  - A novel rapid method for the identification of colonies of Clostridium
      perfringens (key iD Lab M Ltd. Bury, UK) was evaluated. The method consists of a
      test strip containing substrates for pre-formed enzymes selected for optimum
      differentiation of C. perfringens from other clostridia. One hundred and forty
      six strains of clostridia were tested using the key iD strip. The strip
      successfully confirmed the identity of all 73 strains of C. perfringens tested,
      and differentiated these from 73 strains of 20 other clostridial species. C.
      absonum and C. baratii, spedes which are very similar to C. perfringens, could
      also be differentiated by this method. The key iD strip is recommended for
      laboratories as a rapid alternative to more conventional tests for presumptive
      identification of C. perfringens.

PMID- 16887523
TI  - Polyphosphate accumulation among denitrifying bacteria in activated sludge.
AB  - Bacterial polyphosphate accumulation and denitrification are important processes
      in biological removal of nutrients from wastewater. It has been suggested that
      phosphorus accumulators are able to denitrify. However, the bacteria known as the
      most important phosphorus accumulators, belonging to the genus Acinetobacter are
      generally not known to denitrify. To clarify how commonly both physiological
      traits are present in the same organism, we screened 165 isolates from activated
      sludge and wastewater for their ability to denitrify, and the ability of the
      denitrifying isolates to accumulate polyphosphate. Of the 165 isolates, 149 were
      from acetate mineral medium (87 of these identified as Acinetobacter by the API
      20 NE identification system) and 16 were from nutrient broth and nitrate medium.
      Only 15 of 165 isolates tested showed true respiratory denitrification activity.
      In the presence of acetylene they converted more than 80% of 5mM NO3- to N2O in 6
      days. None of the Acinetobacter isolates were among the 15 respiratory
      denitrifiers. The denitrifying isolates were identified as species of
      Pseudomonas, Agrobacterium, Pasteurella, Sphingomonas or could not be identified
      by the API 20 NE identification system. According to the BIOLOG identification
      system the denitrifiers were species of Pseudomonas, Hydrogenophaga, Citrobacter,
      Xanthomonas or they could not be identified. The ability of confirmed
      denitrifiers to accumulate phosphate was measured in experiments where cells
      pregrown under phosphorus limitation were exposed to phosphate (8 mg P/L) under
      aerobic conditions. The rates of excess phosphate uptake varied from 0.3 to more
      than 23 mg P/g dry matter/h. Rates for four isolates were higher than those
      reported for Acinetobacter strains. These results show that polyphosphate
      accumulation and denitrification in activated sludge can be carried out by the
      same organisms.

PMID- 16887524
TI  - Sequence of a 10.5 kbp fragment of Clostridium pasteurianum genomic DNA
      encompassing the hydrogenase I gene and two spore germination genes.
AB  - The gene encoding hydrogenase I from Clostridium pasteurianum had previously been
      cloned and sequenced as part of a 2.3 kbp Sau3A genomic DNA fragment. The
      analysis of the regions surrounding the hydrogenase gene has been extended by
      cloning and sequencing two EcoRI fragments, both partially overlapping the 2.3
      kbp Sau3A fragment. An uninterrupted genomic sequence of 10.5 kbp has thus been
      obtained, including 6.7 kbp upstream of the hydrogenase gene, and 2 kbp
      downstream. The hydrogenase gene is separated by 473 bp from the next open
      reading frame on its 5' side and by 366 bp from the next open reading frame on
      its 3' side. It is preceded by putative promoter regions, and followed by a
      strong transcription termination signal. Therefore the hydrogenase I gene from C.
      pasteurianum probably belongs to a monocistronic operon. This is consistent with
      previous biochemical evidence showing that the enzyme is monomeric. The sequence
      data also show that in the case of this Fe-hydrogenase, in contrast to the NiFe
      hydrogenases, there are no accessory genes cotranscribed with, or located near,
      the structural genes. The sequenced region contains six open reading frames in
      addition to the hydrogenase gene. One of these probably encodes
      phosphatidylserine decarboxylase, and two others are homologous to two of the
      three genes of the gerA and gerB loci (spore germination) from Bacillus subtilis.
      These are the first spore germination gene sequences obtained from a bacterium of
      the genus Clostridium.

PMID- 16887525
TI  - Formate dehydrogenase activity in cells and outer membrane blebs of Desulfovibrio
      gigas.
AB  - Formate dehydrogenase in Desulfovibrio gigas was measured by following the
      release of 14CO2 from radiolabeled formate. Experiments with whole cells using
      sulfate as the electron acceptor revealed optimal formate dehydrogenase activity
      at pH 7.0 and formate utilization followed saturation kinetics. While formate
      dehydrogenase was constitutively produced in pyruvate or lactate media, the
      formate dehydrogenase activity was markedly increased in cells grown with formate
      as the electron donor. In cell-free experiments with methyl viologen or 2,6
      dichlorophenolindophenol, about 1% of the cellular formate dehydrogenase activity
      was present in blebs from the outer membrane. Electron microscopy revealed that
      these blebs were closed structures with diameters ranging from 80-800A and were
      not induced by changes in osmotic pressure or cellular autolysis. Analysis of
      blebs revealed the presence of lipopolysaccharides and two proteins with
      molecular masses of 70 and 53 kDa.

PMID- 16887526
TI  - The anaerobic chamber at the National Institutes of Health.

PMID- 16887527
TI  - The taxonomic status of the fermentative halophilic anaerobic bacteria:
      description of Haloanaerobiales ord. nov., Halobacteroidaceae fam. nov., Orenia
      gen. nov. and further taxonomic rearrangements at the genus and species level.

PMID- 16887528
TI  - Kinetics of Congo-red binding by haemin-limited and haemin-excess cells of
      Porphyromonas gingivalis W50.
AB  - The binding of Congo red to P. gingivalis W50 grown in a chemostat under haemin
      limitation and haemin-excess was quantified. Congo red bound to both haemin
      excess and haemin-limited cells with similar capacity and affinity. Binding of
      Congo red was greater than for ferri- (haemin) or ferroprotoporphyrin IX (haem),
      and was not influenced by redox potential at low added ligand concentrations.
      Both haemin-limited and haemin-excess cells showed positive co-operativity
      towards Congo red binding. Pre-exposure of haemin-limited and haemin-excess cells
      to sub-saturating concentrations of ferriprotoporphyrin IX did not affect Congo
      red binding, whereas pre-exposure of haemin-excess cells to ferroprotoporphyrin
      IX increased binding. Iron protoporphyrin IX binding was enhanced after exposure
      of both haemin-excess and haemin-limited cells to Congo red, especially under
      reducing conditions. These results confirm that Congo red binding cannot be used
      as an indirect measure of haemin binding, nor can Congo red be used to inhibit
      haemin binding to P. gingivalis.

PMID- 16887529
TI  - Identification and strain differentiation of 'Bacteroides fragilis group' species
      and Prevotella bivia by PCR fingerprinting.
AB  - Using single consensus primers of genomic nucleotide sequences, PCR-generated
      fingerprints were used for identification and differentiation of the Bacteroides
      fragilis group (B. fragilis, B. thetaiotaomicron, B. ovatus, B. distasonis, B.
      vulgatus) and Prevotella bivia (B. bivius) by comparing the DNA profiles with
      those of reference strains from the American Type Culture Collection and German
      Culture Collection. When primed by a single primer phage M13 core sequence, intra
      species specific differences and species-specific bands were detected. Using
      primers derived from the evolutionarily conserved tRNA gene sequence, species
      specific patterns were produced. A computer program, GelManager, was used to
      analyze the profiles and generate dendrograms. The correlation coefficients
      determined from the DNA fingerprint profiles of the clinical isolates (using the
      M13 core primer) fell within a narrow range, reflecting a high level of homology
      within the species. Based on the dendrograms, strains of one species were clearly
      differentiated from strains of other species. For comparison, SDS-PAGE analysis
      of whole cell extracts was also performed to obtain protein band patterns of
      various strains. Because of the simplicity of the PCR fingerprinting method and
      the ease of performance of computerized evaluation of data, this technique is a
      useful method for both species and strain differentiation, as well as for
      characterization of Bacteroides species and Prevotella bivia.

PMID- 16887530
TI  - A cytochrome cd1-type nitrite reductase isolated from the marine denitrifier
      Pseudomonas nautica 617: purification and characterization.
AB  - Nitrite reductase (cytochrome cd1) was purified to electrophoretic homogeneity
      from the soluble extract of the marine denitrifying bacterium Pseudomonas nautica
      strain 617. Cells were anaerobically grown with 10 mM nitrate as final electron
      acceptor. The soluble fraction was purified by four successive chromatographic
      steps and the purest cytochrome cd1 exhibited an A280
      nm(oxidized)/A410nm(oxidized) coefficient of 0.90. In the course of purification,
      cytochrome cd1 specific activity presented a maximum value of 0.048 units/mg of
      protein. This periplasmic enzyme is a homodimer and each 60 kDa subunit contains
      one heme c and one heme d1 as prosthetic moieties, both in a low spin state.
      Redox potentials of hemes c and d1 were determined at three different pH values
      (6.6, 7.6 and 8.6) and did not show any pH dependence. The first 20 amino acids
      of the NH2-terminal region of the protein were identified and the sequence showed
      45% identity with the corresponding region of Pseudomonas aeruginosa nitrite
      reductase but no homology to Pseudomonas stutzeri and Paracoccus denitrificans
      enzymes. Spectroscopic properties of Pseudomonas nautica 617 cytochrome cd1 in
      the ultraviolet-visible range and in electron paramagnetic resonance are
      described. The formation of a heme d1 -nitric-oxide complex as an intermediate of
      nitrite reduction was demonstrated by electron paramagnetic resonance
      experiments.

PMID- 16887531
TI  - Malate metabolism by Desulfovibrio gigas and its link to sulfate and fumarate
      reduction: purification of the malic enzyme and detection of NAD(P)+
      transhydrogenase activity.
AB  - Malate metabolism was investigated in lactate grown cells of Desulfovibrio gigas
      ; 3 mol of malate are converted into 2 mol succinate and 1 mol acetate. The malic
      enzyme (L-malate:NADP+ oxidoreductase) was purified to homogeneity and partially
      characterized. The enzyme is monomeric with molecular weight of 45 kDa. Its
      spectrum has no visible absorption and the activity is stimulated by K+ and Mg2+.
      The presence of an NAD(P)+ transhydrogenase, the observation of partial reduction
      of adenylylsulfate reductase by NADH (via NADH-rubredoxin oxidoreductase) and
      evidence for NADH-linked fumarate reductase activity support the involvement of
      pyridine nucleotides in the electron pathway toward the reduction of sulfur
      compounds and/or fumarate. An electron transfer chain to fumarate is proposed,
      taking into consideration these results and the stoichiometry of end-products
      derived from malate dismutation.

PMID- 16887532
TI  - Summary of the ASM first international conference on the molecule genetics and
      pathogenesis of the clostridia.

PMID- 16887533
TI  - Genomic clusters and codon usage in relation to gene expression in oral Gram
      negative anaerobes.

PMID- 16887534
TI  - Acid exposure enhances sporulation of certain strains of Clostridium perfringens.
AB  - A gastroenteritis results when Clostridium perfringens is ingested in high
      numbers and sporulates releasing enterotoxin in the intestines. Since the
      organism must pass through the stomach, its ability to form spores may be
      affected by the acidic environment. Five strains of C. perfringens were exposed
      to acidic conditions and then assessed for survival and their ability to form
      spores. An acidic pH environment kills the bacteria over time but surviving cells
      are able to recover and form spores. Two of the five strains demonstrated
      enhanced sporulation following a 30-min exposure to a pH 2 environment. For four
      of the strains tested, enterotoxin concentrations were higher from acid-exposed
      cells than from untreated cells. Exposure to a pH 3.5 environment did not affect
      sporulation when compared to an untreated control. Bacteria in the stationary
      phase of growth were the most able to resist the acid and sporulate. The results
      indicate that some strains will produce more spores and enterotoxin following
      exposure to an acidic environment.

PMID- 16887535
TI  - Antibiotic susceptibility of Bacteroides fragilis group strains in Hungary.
AB  - Resistance rates to different antibiotics of 495 Bacteroides fragilis group
      strains were followed between 1987 and 1994 in Hungary. In 1992 the strains were
      collected in three different laboratories, whereas during the other periods
      strains were isolated in one centre. Metronidazole, chloramphenicol, imipenem and
      amoxicillin/clavulanic acid were the most active drugs. A high level of
      resistance was observed in 1987 for ampicillin (88% at > 4 mg/L), erythromycin
      (51% at > 4 mg/L), tetracyclin (53% at > 8 mg/L) and clindamycin (27% at > 4
      mg/L). The same level of resistance was seen during the further years for
      clindamycin and ampicillin. Resistance to cefoxitin increased from 6% to 11%
      between 1987 and 1993/1994. No differences in resistance rates were observed
      between the strains collected in the three centers. For 100 strains, the results
      of the E test were compared with those of the micro-broth dilution test, both
      being used routinely for testing the antibiotic susceptibility of Bacteroides
      fragilis group strains in this period.

PMID- 16887536
TI  - Co-culture of Bifidobacterium adolescentis and Bacteroides thetaiotaomicron in
      arabinogalactan-limited chemostats: effects of dilution rate and pH.
AB  - The effects of dilution rate (D = 0.04-0.38/h) and pH (5.0-6.5) on co-cultures of
      Bifidobacterium adolescentis and Bacteroides thetaiotaomicron were studied in
      arabinogalactan-limited chemostats. B. thetaiotaomicron outcompeted B.
      adolescentis at all dilution rates at culture pH values between 5.0 and 6.0,
      although the bifidobacterium was always detected in the fermenters. At pH 6.5,
      however, B. adolescentis predominated in co-cultures at dilution rates above
      0.24/h. Arabinogalactan degrading enzymes (beta-galactosidase, alpha
      arabinofuranosidase) were strongly catabolite repressed in bacteroides at high
      dilution rates, but were constitutive and growth rate-associated in B.
      adolescentis. The increased competitiveness of B. adolescentis at high specific
      growth rates was not related to its ability to synthesise increased levels of
      depolymerising enzymes. Measurements of residual carbohydrate in pure and mixed
      culture chemostats showed that the bacteroides extensively digested the galactose
      backbone of the polymer, and to a lesser degree, the arabinose sidechains.
      Nevertheless, arabinose monomers and oligosaccharides (d.p. < 10) accumulated in
      these cultures under all growth conditions. In contrast, the bifidobacterium
      utilized considerably less arabinogalactan than the bacteroides, and this was
      reflected in the mixed culture studies. These experiments demonstrate that B.
      thetaiotaomicron was able to compete most successfully for this plant cell wall
      polysaccharide under nutritional, physiological and environmental conditions
      broadly similar to those encountered in the human colon, and indicate the
      existence of synergistic interactions between the two organisms that were growth
      rate dependent.

PMID- 16887537
TI  - Purification and characterization of a DnaK-like and a GroEL-like protein from
      Porphyromonas gingivalis.
AB  - Heat-shock proteins of Porphyromonas gingivalis were demonstrated and two of them
      were purified and further characterized. The amplified de novo synthesis of two
      different proteins, with apparent molecular weights of 75 kDa and 68 kDa, was
      observed by autofluorography when a P. gingivalis culture incubated in a 14C
      labeled amino acid mixture was shifted from 37 degrees C to 44 degrees C. Both
      proteins possessed ATP-binding abilities and were purified to almost homogeneity
      employing affinity chromatography on ATP-agarose followed by preparative SDS
      PAGE. Purified 75 kDa and 68 kDa proteins had isoelectric points of 4.4 and 4.6,
      respectively. They were shown to be immunoreactive with commercial anti-DnaK and
      anti-GroEL polyclonal antibodies, respectively. Immunoblotting analysis of whole
      cells using antiserum raised against each purified protein from P. gingivalis,
      confirmed elevated synthesis of both proteins during thermal shock. A GroEL
      protein reacted strongly with antiserum against the 68 kDa protein. However, a
      DnaK protein reacted weakly with antiserum to the 75 kDa protein. Analysis of the
      N-terminal amino acid sequence of the DnaK-like protein (75 kDa) showed a high
      degree of homology with those of the HSP70 family including both prokaryotic and
      eukaryotic cells. The N-terminal amino acid analysis of the GroEL-like protein
      (68 kDa) indicated that it was identical to those of cloned GroEL homologues from
      P. gingivalis.

PMID- 16887539
TI  - Toluene metabolism under anaerobic conditions: a review.

PMID- 16887540
TI  - The aerobic and anaerobic microbiology of pustular acne lesions.
AB  - Specimens from 32 pustular acne lesions that were inoculated on media supportive
      for the growth of aerobic and anaerobic bacteria showed bacterial growth. Only
      aerobic or facultative bacteria were recovered in 15 (47%) specimens, only
      anaerobic bacteria in 11 (34%) specimens, and mixed aerobic and anaerobic
      bacteria in 6 (18%) specimens. A total of 57 isolates, 31 anaerobes (1.0 per
      specimen) and 26 aerobes (0.8 per specimen) were recovered. The predominant
      isolates were Staphylococcus sp. (19 isolates), Peptostreptococcus sp. (15), and
      Propionibacterium sp. (10). Twelve (37.5%) of the comedones yielded only one
      organism. This retrospective study highlighted the polymicrobial nature of over
      two-thirds of culture positive pustular acne lesions and suggests the potential
      for pathogenic role of aerobic and anaerobic organisms other than P. acnes and
      Staphylococcus sp. in acne vulgaris.

PMID- 16887541
TI  - United States National Hospital Survey of anaerobic culture and susceptibility
      methods, II.
AB  - To assess the status of clinical anaerobic bacteriology in the United States, we
      surveyed (by means of a questionnaire) 120 hospitals selected at random with bed
      capacities of 200-1000, and we received responses from 78 (65%), all of which
      performed some degree of clinical anaerobic microbiology. Separate anaerobic
      blood culture bottles were used by 73 labs (94%) (median, 450 specimens/mo): 56%
      used Bactec 7, 27 or 37; 15% used 'BacT-Alert'; 11% used Columbia broth; 5% used
      thioglycolate and 'lytic'; 3% each used, Dupont Isolator, Supplemented peptone or
      other media. Selective media was used for primary anaerobe isolation by 89% labs
      which included: LKV, 76%; PEA, 53%; BBE, 31%; CNA, 28%; 'CDC', 12%. Sixty labs
      (78%) stored anaerobes after isolation (median 7 days), most using blood agar
      plates (31%), chopped meat (26%) or thioglycolate broth (27%) either for further
      identification (30 out of 78) or susceptibility testing (33 out of 78), if
      clinically indicated. Only 23% performed routine anaerobic susceptibility testing
      of clinical isolates. Of the 77% that do not perform susceptibility studies, 59%
      would not even perform them upon physician request; 30% relied on published
      surveys; 68% did not publish results of anaerobic susceptibility in annual
      summaries. When susceptibility testing was performed, the test agents selected
      were related to availability on a commercial system (21), NCCLS recommendation
      (20), hospital formulary (15) or hospital committee input (20). Nine of 78 labs
      (12%) had discussed stopping or decreasing the performance of both anaerobic
      bacteriology and susceptibility testing. Despite educational and published
      guidelines, clinical anaerobic bacteriology is not uniformly practiced and could
      be improved. In addition, an educational effort must be made in order to stress
      the relevance and increase performance of anaerobic bacteriology.

PMID- 16887542
TI  - A new method for routine isolation of oral treponemes using U-tubes and pectin
      medium.
AB  - Determination of the composition of the oral microflora has traditionally been
      based on cultivation. Treponemes are prevalent in many oral infections but,
      unfortunately, are not regularly cultured. In this study a new method was
      established for routine isolation of oral treponemes from clinical samples.
      Bacterial samples from 47 periodontal pockets and 4 endodontic infections were
      incubated anaerobically under nitrogen atmosphere at 37 degrees C in U-tubes
      containing pectin medium. In the U-tube a 'bacterial sample side' and a 'sterile
      medium side' were established on separate sides of a membrane filter and an agar
      plug. Using this method we were able to isolate viable treponemes from all
      bacterial samples. This was in contrast to previously established methods such as
      the agar dilution technique, the technique involving the membrane filter placed
      on the surface of solid agar media and the well in agar plate technique. We
      believe that the 'U-tube method' is a valuable supplement to previously described
      techniques in routine isolation of treponemes from clinical samples.

PMID- 16887543
TI  - Characterization of tannin acylhydrolase activity in the ruminal bacterium
      Selenomonas ruminantium.
AB  - A strain of the anaerobe Selenomonas ruminantium subsp. ruminantium that is
      capable of growing on tannic acid or condensed tannin as a sole energy source has
      been isolated from ruminal contents of feral goats browsing tannin-rich Acacia
      sp. Growth on tannic acid was accompanied by release of gallic acid into the
      culture medium but the bacterium was incapable of using gallic acid as a sole
      energy source. Tannin acylhydrolase (EC 3.1.1.20) activity was measured in crude
      cell-free extracts of the bacterium. The enzyme has a pH optimum of 7, a
      temperature optimum of 30-40 degrees C and a molecular size of 59 kDa. In crude
      extracts, the maximal rate of gallic acid methyl ester hydrolysis was 6.3
      micromol min(-1) mg(-1) of protein and the K(m) for gallic acid methyl ester was
      1.6 mM. Enzyme activity was displayed in situ in polyacrylamide and isoelectric
      focusing gels and was demonstrated to increase 17-fold and 36-fold respectively
      when cells were grown in the presence of gallic acid methyl ester or tannic acid.

PMID- 16887544
TI  - Localization of carbohydrate and DNA in cyst-like structures from a human
      intestinal spirochaete.
AB  - This study examined the cyst-like structures found in human intestinal
      spirochaetes by transmission electron microscopy and by histochemical and
      immunocytochemical analysis. A human intestinal spirochaete which morphologically
      resembled other intestinal spirochaetes was grown anaerobically on blood agar
      plates and in Tryptone Soya broth (Oxoid) and harvested by centrifugation after 8
      days growth. Specimens were either conventionally fixed for transmission electron
      microscopy or fixed in 0.5% glutaraldehyde in 0.1M sodium cacodylate buffer and
      embedded in LR White resin for immunocytochemistry. En bloc histochemical
      investigation using a periodic acid-thiosemicarbazide-silver proteinate technique
      was undertaken for the localization of carbohydrate. A post-embedding immunogold
      labelling technique was used on ultrathin sections to label DNA. Results from the
      histochemical study demonstrated a reaction product which was confined to the
      cytoplasm of mature spirochaetes and in the central bodies within the cysts.
      Immunogold labelling demonstrated the presence of DNA in both the mature
      protoplasmic cylinders and in the central bodies. The results of the present
      study indicate that spirochaetal cysts are highly organized structures, which
      contain both DNA and carbohydrate. These findings are compatible with the view
      that these structures have a functional role rather than representing
      degenerative artifacts.

PMID- 16887545
TI  - Cleavage of di- and tripeptides by Prevotella ruminicola.
AB  - The final step in the conversion of protein to amino acids by the common Gram
      negative rumen bacterium, Prevotella (formerly Bacteroides) ruminicola , is the
      cleavage of di- and tripeptides. Dipeptidase and tripeptidase activities were
      predominantly cytoplasmic, and toluene treatment increased the rate of Ala2 and
      Ala3 hydrolysis by whole cells, suggesting that transport limited the rate of
      hydrolysis of extracellular di- and tripeptides. The hydrolysis of Ala2 and Ala3
      by whole cells was not affected by protonophores, ionophores or
      dicyclohexylcarbodiimide, but Ala2 hydrolysis by EDTA-treated cells was inhibited
      by the Ca2+/H+ ionophore, tetronasin. Ala3 hydrolysis was not affected by
      protonophores or ionophores in EDTA-treated cells. The dipeptidase of strain M384
      was inhibited > 99% by 1,10-phenanthroline and 39% by EDTA but not other protease
      inhibitors, consistent with the enzyme being a metalloprotease. Tripeptidase was
      insensitive to protease inhibitors, except for a 33% inhibition by EDTA. Cleavage
      of tripeptides occurred at the bond adjacent to the N-terminal amino acid.
      Distinct di-, tri- and oligopeptidase peaks were obtained by anion-exchange
      liquid chromatography of disrupted cells. Banding patterns on native PAGE using
      activity staining also indicated that P. ruminicola M384 had separate single
      dipeptidase and tripeptidase enzymes which hydrolysed a range of peptides. The
      dipeptidase of strain M384 was different from other strains of P. ruminicola:
      strains GA33 and B(1)4 had activities which ran at the same R(f); strain GA33 had
      another band of lower activity; strain 23 had two bands different from those of
      the other strains. The tripeptidases ran at the same R(f) for the different
      strains. Dipeptidase activity of all strains was inhibited by 1,10-phenanthroline
      on gels. Gel permeation chromatography indicated that the M(r) of the
      dipeptidases from strains M384 and B(1)4 were 115,000 and 114,500 respectively,
      and 112,500 and 121,500 for the corresponding tripeptidases. Thus the metabolism
      of small peptides by P. ruminicola involves separate permeases and intracellular
      peptidases for di- and tripeptides.

PMID- 16887546
TI  - Swarming characteristics of Proteus mirabilis under anaerobic and aerobic
      conditions.
AB  - Nutrients have a pronounced effect on the growth and swarming behaviour of
      Proteus mirabilis 7002. Iron, zinc, amino acids, and dioxygen are important for
      rapid growth and normal swarming. Anaerobically grown cultures of P. mirabilis
      7002 were unable to swarm on anaerobically maintained rich nutrient agar. Upon
      exposure to aerobic conditions, P. mirabilis 7002 resumed swarming behaviour.
      Scanning electron microscopy was used to demonstrate the presence of community
      organization and mature rafts during normal swarming. These results support the
      importance of dioxygen and redox status in cell differentiation.

PMID- 16887547
TI  - Localization of cytochromes in the outer membrane of Desulfovibrio vulgaris
      (Hildenborough) and their role in anaerobic biocorrosion.
AB  - A protocol was developed whereby the outer and cytoplasmic membranes of the
      sulfate-reducing bacterium Desulfovibrio vulgaris (Hildenborough) were isolated
      and partially characterized. The isolated outer membrane fractions from cultures
      grown under high (100 ppm) and low (5 ppm) Fe2+ conditions were compared by SDS
      PAGE electrophoresis, and showed that several protein bands were derepressed
      under the low iron conditions, most notably at 50 kDa, and 77.5 kDa. Outer
      membrane isolated from low iron cultured cells was found to contain two proteins,
      77.5 kDa and 62.5 kDa in size, that reacted with a heme-specific stain and were
      referred to as high molecular weight cytochromes. Studies conducted on the low
      iron isolated outer membrane by a phosphate/mild steel hydrogen evolution system
      showed that addition of the membrane fraction caused an immediate acceleration in
      H2 production. A new model for the anaerobic biocorrosion of mild steel is
      proposed.

PMID- 16887548
TI  - Summary of Clostridium difficile workshop and symposium, 4-5 May 1995, Tours and
      Paris, France.

PMID- 16887551
TI  - Genetics of 5-nitroimidazole resistance in Bacteroides species.

PMID- 16887552
TI  - Winogradsky discovered a new modus vivendi.

PMID- 16887549
TI  - Anaerobes response to oxygen: the sulfate-reducing bacteria.

PMID- 16887553
TI  - Chaim Weizmann: from fermentation chemist to president of Israel.

PMID- 16887554
TI  - Comparative growth of Porphyromonas gingivalis strains in a defined basal medium.
AB  - Porphyromonas gingivalis is an asaccharolytic bacterium whose metabolism is
      dependent on the uptake of small peptides and amino acids. The aim of this work
      was to study the growth of P. gingivalis in a defined basal medium (DBM)
      supplemented with various sources of proteins. The strain 49417 as well as other
      virulent isolates could grow in DBM containing 1% bovine serum albumin (BSA).
      Cells cultivated under this condition showed a slightly modified protein profile,
      and expressed hemagglutinating as well as proteolytic activities. Other natural
      proteins under investigation could not support the growth in the DBM. On the
      other hand, the strain 33277 as well as other avirulent strains of P. gingivalis
      could not use BSA as a substrate. The ability of P. gingivalis to grow in DBM-BSA
      is not entirely dependent on its ability to degrade the protein substrate as
      strain 33277 was able to extensively hydrolyse the molecule. Differences in
      either metabolic enzymes or peptide transport mechanisms may explain the
      distinctive behavior between virulent and avirulent strains. Data from this work
      suggest a relationship between nutritional requirements and virulence of P.
      gingivalis in an animal model. The DBM-BSA may represent a more appropriate
      medium for studies on the physiology of P. gingivalis.

PMID- 16887555
TI  - The rumen: a unique source of enzymes for enhancing livestock production.
AB  - Increasing competition in the livestock industry has forced producers to cut
      costs by adopting new technologies aimed at increasing production efficiency. One
      particularly promising technology is feeding enzymes as supplements for animal
      diets. Supplementation of diets for non-ruminants (e.g., swine and poultry) with
      fibrolytic enzymes, such as cellulases, xylanases and beta-glucanases, increases
      the feed conversion efficiency and growth rate of the animals. Enzymatic
      hydrolysis of plant cell wall polymers (e.g., cellulose, xylan, beta-glucans)
      releases glucose and xylose and eliminates the antinutritional effects of beta
      glucans and arabinoxylans. Enzyme supplementation of diets for ruminants has also
      been shown to improve growth performance, even though the rumen itself represents
      the most potent fibrolytic fermentation system known. Implementation of this
      technology in the livestock industry has been limited largely because of the cost
      of development and production of enzymes. Over the last decade, however,
      developments in recombinant DNA technology have increased the efficiency of
      existing microbial production systems and facilitated exploitation of alternative
      sources of industrial enzymes. The ruminal ecosystem is among the novel enzyme
      sources currently being explored. Understanding the role of enzymes in feed
      digestion through characterization of the enzymology and genetics involved in
      digestion of feedstuffs by ruminants will provide insight required to improve the
      products currently available to producers. Characterization of genes encoding a
      variety of hydrolytic enzymes, such as cellulases, xylanases, beta-glucanases,
      amylases, pectinases, proteases, phytases and tannases, will foster the
      development of more efficacious enzyme supplements and enzyme expression systems
      for enhancing nutrient utilization by domestic animals. Characteristics of the
      original source organism need no longer restrict the production of a useful
      enzyme. Recent reports of transgenic plants expressing fibrolytic or phytase
      activity and of transgenic mice able to produce endoglucanase in the pancreas
      speak to the feasibility of improving feed digestion through genetic modification
      of the feedstuffs and the animals.

PMID- 16887556
TI  - Clostridium difficile: an update on virulence mechanisms.

PMID- 16887557
TI  - Microbial anaerobic aromatic metabolism.

PMID- 16887558
TI  - Peptostreptococcus vaginalis or Peptostreptococcus prevotii? Identification and
      clinical importance of a new species of Peptostreptococcus.
AB  - Peptostreptococcus vaginalis is a recently described species of Gram-positive
      anaerobic coccus. We report one case in which P. vaginalis was isolated in pure
      culture from an abscess on the upper arm, and summarise nine further cases where
      it was isolated in mixed culture from other superficial sites, particularly
      infected leg ulcers. We suggest that clinical strains of P. vaginalis have
      probably been described in the past as Peptostreptococcus prevotii, a species
      which has frequently been reported from clinical surveys of anaerobic infections;
      their relative importance and appropriate treatment are discussed. Preformed
      enzyme profiles provide a simple method of identification accessible to routine
      diagnostic laboratories; when clinically significant isolates of GPAC are
      isolated in pure growth, they should be identified to the species level by use of
      preformed enzyme kits.

PMID- 16887559
TI  - Production and characterization of monoclonal antibodies to a Veillonella species
      from a continuous-flow culture system of chicken cecal bacteria.
AB  - Administering native intestinal flora to newly hatched chicks protects against
      cecal Salmonella colonization, and is known as competitive exclusion. Continuous
      flow culture systems have been used to maintain defined competitive exclusion
      cultures. We have recently demonstrated that such a stable continuous-flow
      culture, CF3, contains 29 bacterial strains representing ten genera. Broiler
      chicks treated with CF3 are protected against Salmonella colonization of the
      ceca. Such protection is correlated with elevated concentrations of proprionic
      acid in the cecal contents of treated chicks. In this study we report on the
      preparation and characterization of monoclonal antibodies to one of the
      proprionic acid producing anaerobes contained in CF3, namely Veillonella CF3.
      Five different monoclonal antibodies were characterized with respect to: (1)
      isotype; (2)Veillonella specificity as judged by cross-reactivity profiles with
      other bacteria; (3) sensitivity as measured by the limit of detection of the
      number of colony forming units of Veillonella; and (4) antigen recognition of
      Veillonella by Western Blot analysis. These antibodies have been used to
      enumerate Veillonella in both the CF3 cultures and in the ceca of young chicks.

PMID- 16887560
TI  - Peptidases of the rumen bacterium, Prevotella ruminicola.
AB  - Prevotella (formerly Bacteroides) ruminicola is a numerous rumen bacterium which
      plays a significant role in the metabolism of proteins and peptides in the rumen.
      Measurement of the hydrolysis of synthetic aminopeptidase substrates by sonicated
      extracts and whole cells of different species of rumen bacteria indicated that P.
      ruminicola had the greatest range and specific activity of dipeptidyl peptidases
      among the species tested. Streptococcus bovis hydrolysed some dipeptidyl
      peptidase substrates to a lesser extent, and several species broke down Ala2-p
      nitroanilide, including Ruminobacter amylophilus, Ruminococcus spp. and
      Veillonella parvula. Dipeptidyl peptidases, which cleave dipeptides from the
      amino-terminus of longer peptides, were much more active than aminopeptidases
      removing single amino acids in P. ruminicola. Ion-exchange chromatography of
      sonicated extracts of P. ruminicola M384 revealed at least four distinct
      activities: one hydrolysed Ala2-p-nitroanilide, ValAla-p-nitroanilide, Ala4and
      Ala5; another was an O2-sensitive activity hydrolysing GlyArg-4
      methoxynapthylamide, ArgArg-4-methoxynaphthylamide, Gly5 and ValGlySerGlu,
      similar to dipeptidyl peptidase type I DPP-1); a third hydrolysed GlyPro-p
      nitroanilide and GlyPro-4-methoxynapthylamide and was similar to dipeptidyl
      peptidase type IV XDPP-4); a fourth broke down LysAla-4-methoxynaphthylamide. All
      of the enzymes, and particularly those active against Ala2-p-nitroanilide and
      GlyPro-p-nitroanilide, were inhibited by serine protease inhibitors, and all
      except DPP-4 were inhibited by EDTA. Both DPP-1 and the enzyme hydrolysing LysAla
      4-methoxynaphthylamide were inhibited strongly by iodoacetate. DPP-4 was
      inhibited completely by diprotin A. Competitive inhibition experiments suggested
      that DPP-1 was less important than the other enzymes in the breakdown of peptide
      mixtures.

PMID- 16887561
TI  - Polysaccharide inducible outer membrane proteins of Bacteroides xylanolyticus X5
      1.
AB  - Little is known about how bacteria degrade structural polysaccharides or the
      regulatory systems that control this degradation. Bacteroides xylanolyticus X5-1
      is a Gram-negative, anaerobic bacterium that can grow on structural
      polysaccharides such as xylan and pectin. In order to determine the response of
      this organism to specific substrates,B. xylanolyticus was grown on a variety of
      mono-, di-, and polysaccharides. Electrophoretic analysis revealed no distinct
      differences in the polypeptide profile of the inner membrane enrichments of cells
      grown on different carbohydrates. However, distinct differences in protein
      composition of outer membrane enrichments were clearly observed. The profiles
      from cells grown on starch, xylan, and pectin were distinct from each other and
      their respective monosaccharide. In addition, cells initially grown on xylan did
      not alter their total membrane protein composition after three generations of
      growth in medium containing xylan and glucose. Thus,B. xylanolyticus X5-1 altered
      its outer membrane protein composition in response to specific polysaccharide
      substrates, but analysis of this specific response revealed no evidence that
      glucose was preferred over xylan as a substrate.

PMID- 16887562
TI  - Dilution rate increases production of plant cell-wall degrading enzymes by
      anaerobic fungi in continuous-flow culture.
AB  - The gut anaerobic fungi,Neocallimastix hurleyensis and aOrpinomyces sp., were
      grown in 100 mL batch and continuous-flow cultures on wheat straw at a
      concentration of 80 g dry matter/L of culture liquid. In batch cultures,N.
      hurleyensis and Orpinomyces sp. degraded only ca. 9% and 5% of the wheat straw,
      respectively. In continuous-flow cultures, however, the two fungi degraded 52-56%
      of the apparent dry matter of wheat straw. Both fungi were able to produce
      greater quantities (up to x 30) of cell-wall degrading enzymes (CMCase, xylanase,
      beta-glucosidase and beta-xylosidase) in continuous-flow cultures than in the
      corresponding batch cultures. Increasing the dilution rate in continuous-flow
      culture resulted in the production of increased enzyme activity for all the
      measured cell-wall degrading enzymes, with proportional relationships between
      dilution rate and the cumulative activities of beta-glucosidase and beta
      xylosidase. Dilution rates, however, had no consistent effect on the cumulative
      production of the fermentation end-products, acetate, formate, D- and L-lactate
      from both fungi. In addition to acetate and formate,N. hurleyens is produced D-
      and L-lactate in both batch and continuous-flow cultures, whereas only trace
      amounts of L-lactate were detected in the Orpinomyces sp. cultures.

PMID- 16887563
TI  - Distinction of Prevotella intermedia and Prevotella nigrescens from endodontic
      bacteremia through their fatty acid contents.
AB  - Prevotella nigrescens has recently been recognized as a new species distinct from
      Prevotella intermedia. The distinction is based largely on DNA-DNA hybridization,
      electrophoretic migration of malate and glutamate dehydrogenase, and peptidase
      and lipase activities of type strains. Gas chromatography of cellular fatty acids
      can be a useful adjunct for characterization and identification of bacterial
      species. In the present study, cellular fatty acid profiles were determined for
      seven strains of P. intermedia and six strains of P. nigrescens. Six of these 13
      strains were isolated from the root canal and blood of three patients during
      endodontic therapy of teeth with Asymptomatic apical periodontitis. The bacteria
      were cultivated anaerobically in 10 mL prereduced anaerobically sterilized
      peptone-yeast extract-glucose broth for 24 h. Dried cells of each isolate were
      methanolysed and their fatty acid contents determined by the Microbial
      Identification System software package by MIDI. The data were treated by
      principal component analysis, which distinguished P. nigrescensfromP. intermedia.
      Cellular fatty acid profiles of these strains of the species in blood matched the
      profiles of their respective root canal isolates, as demonstrated by Euclidean
      Distance Square assessment. This suggested that the organisms in the root canal
      had spread to the bloodstream during endodontic treatment.

PMID- 16887565
TI  - Pharmaceutical probiotics for the treatment of anaerobic and other infections.
AB  - Pharmaceutical probiotics have been used as alternative treatments or
      preventative therapies for a variety of clinical diseases. The overuse of
      antibiotics and emergence of multiple-antibiotic resistant pathogens has
      refocused clinical attention on the field of probiotics. Anaerobic infections
      which seem to respond well to probiotics are infections which involve the
      disruption of normal microbial flora. Gastrointestinal infections (travelers'
      diarrhea, antibiotic-associated diarrhea,Clostridium difficile disease, rotavirus
      diarrhea) have been studied using the following pharmaceutical
      probiotics:Saccharomyces boulardii, Lactobacillus casei GG, Lactobacillus
      acidophilus, Lactobacillus bulgaricus, Bifidobacterium bifidum, Streptococcus
      thermophilus and Enterococcus faecium. Vaginitis has been experimentally studied
      using L. acidophilus and L. casei GG. The efficacy, safety and mechanisms of
      action of these various probiotics are reviewed. Requirements for drug approval
      are similar for biologic probiotics and new drug entities and these requirements
      involve preclinical tolerability studies, pharmacokinetic studies and large, well
      controlled blinded clinical trials.

PMID- 16887567
TI  - Bilophila wadsworthia: a unique Gram-negative anaerobic rod.
AB  - Although comprising less than 0.01% of the normal human gastrointestinal
      microbiota, Bilophila wadsworthia is the third most common anaerobe recovered
      from clinical material obtained from patients with perforated and gangrenous
      appendicitis. Since its discovery in 1988, B. wadsworthia has been recovered from
      clinical specimens associated with a variety of infections, including sepsis,
      liver abscesses, cholecystitis, Fournier's gangrene, soft tissue abscesses,
      empyema, osteomyelitis, Bartholinitis, and hidradenitis suppurativa. In addition,
      it has been found in the saliva and vaginal fluids of asymptomatic adults and
      even in the periodontal pockets of dogs. The organism is a saccharolytic,
      fastidious, and is easily recognized by its strong catalase reaction with 15%
      H2O2, production of hydrogen sulfide, and growth stimulation by bile (oxgall) and
      pyruvate. Approximately 75% of strains are urease positive. When grown on
      pyruvate-containing media, > 85% of strains demonstrate beta-lactamase
      production. Ribosomal RNA-based phylogenetic studies show Bilophila to be a
      homogeneous species, most closely related to Desulfovibrio species. Both
      adherence to human cells and endotoxin have been observed, and preliminary work
      suggests that environmental iron has a role in expression of outer membrane
      proteins. Penicillin-binding proteins appear to mediate the organism's
      susceptibility to at least some beta-lactam agents, which induce spheroplast
      formation that results in a haze of growth on agar dilution susceptibility test
      plates which is difficult to interpret. Bilophilastrains are inhibited in vitro
      by most antibiotics.

PMID- 16887566
TI  - Anaerobes isolated from clinical material over three years.
AB  - Data on anaerobic bacteria isolated from clinical specimens at the bacteriology
      department within the 3-year period (1992-1994) were analysed. Anaerobic
      cultivation was carried out in all aspirates and swabs were transferred in
      transport media in syringes or blood cultures. Established growth occurred in all
      samples cultivated in thioglycollate broth after 4 days of incubation.
      Cultivation methods included enrichment media, GasPak jar, and API (BioMerieux)
      for final identification. A sulfite-reduction test using the Wilson-Blair medium
      and the Ellner-Smith sporulation medium was also used for the isolation of
      Clostridium perfringens. Anaerobes were diagnosed in 899 samples. Wound swabs
      (266 samples) and aspirates (106 samples) were the most common clinical material
      used. In total, 964 anaerobes were isolated: Peptostreptococcus species (299
      strains), Eubacterium species (188 strains), Propionibacterium species (153
      strains), Bacteroides fragilis(149 strains), Bacteroides species (95 strains) and
      Clostridium perfringens(80 strains).

PMID- 16887568
TI  - Enterotoxigenic Bacteroides fragilis in Hungary.
AB  - Bacteroides fragilis, which constitutes about 1% of the colonic microflora in
      humans, is the most frequent anaerobic species involved in abscesses, soft-tissue
      infections and bacteraemias. Additionally, enterotoxigenic strains of B. fragilis
      have been demonstrated to be associated with diarrhoea in domestic animals and
      humans. Enterotoxigenic strains of B. fragilis derived from stool specimens and
      from infectious processes produce a toxin which induces a cytotoxic response in
      HT-29 colon carcinoma cells. These findings prompted us to investigate the
      prevalence of enterotoxigenic strains of B. fragilis isolated from various
      clinical specimens in Hungary. A total of 134 strains were collected from
      different clinical settings: 74 from infectious processes, 20 from stools of
      healthy subjects and 40 from the faeces of patients with diarrhoea where no other
      enteric pathogen could be isolated. Cell culture assays with HT-29 cells were
      performed on the filtered culture supernatants of the isolated strains. Of the
      134 strains, 34 (25.3%) proved toxin-positive. The presence of free toxin was
      also observed in 20 of 50 (40%) of the faeces of adults with diarrhoea.

PMID- 16887569
TI  - Binding of extracellular matrix proteins to the surface of Bacteroides spp.
AB  - The binding of fibronectin an vitronectin to 207 Bacteroides strains and the
      binding of collagen and sialoproteins to 55 Bacteroides strains were investigated
      by means of latex agglutination tests. The binding of fibronectin, collagen and
      lactoferrin to the same 55 strains was also tested by using 125I-labelled
      proteins. The 207 strains, belonging to ten Bacteroides species, were isolated
      from different infections (51%) and from faeces of healthy subjects (49%). Most
      of the strains displaying fibronectin binding belonged in the species B. fragilis
      or B. vulgatus. The binding could be inhibited by preincubation of the cells with
      an excess amount of fibronectin. No inhibition of the binding was observed with
      carbohydrates. The vitronectin binding of the strains was less common, but was
      always observed to accompany fibronectin binding. None of the examined 55 strains
      exhibited any binding to fetuin or asialofetuin. The radiolabelling method
      indicated a low binding to 125I-fibronectin. The binding of 125I-collagen-I and
      125I-lactoferrin in the Bacteroides strains tested was higher than that of 125I
      fibronectin.

PMID- 16887570
TI  - Periodontal microflora of HIV infected patients with periodontitis.
AB  - The aim of this study was to determine the microbial profile of periodontal
      lesions in HIV seropositive patients and to compare it with rapidly progressing
      periodontal lesions in systemically healthy patients. The subgingival microflora
      of 20 CDC II, 20 CDC III, 20 CDC IV/V and 20 systemically healthy patients with
      rapidly progressing periodontitis was examined. Four sites with greatest probing
      depth in each patient were selected for microbiological sampling. The samples
      were cultured aerobically and anaerobically for bacterial isolation using
      selective and non-selective media. Isolates were characterized to species level
      by conventional biochemical tests and various identification kits. The microflora
      of periodontitis lesions within the three stages of the HIV infection was similar
      to that of progressing periodontitis in systemically healthy adults including
      Campylobacter rectus, Capnocytophaga spp., Fusobacterium nucleatum, Porphyromonas
      gingivalis, Prevotella intermedia, Selenomonas spp. and Peptostreptococcus
      micros. However, HIV seropositive periodontitis lesions harboured a range of
      exogenous pathogens rarely associated with common types of periodontitis
      including Staphylococcus aureus, Enterobacter cloaca, Pseudomonas aeruginosa,
      Candida albicans, Enterococcus faecalis, Enterococcus avium, Clostridium
      difficile, Aspergillus fumigatus, Klebsiella pneumoniae and Mycoplasma
      incognitum. The lack of immune effector and regulatory cells in HIV infected
      patients could in fact explain the increase of some opportunistic pathogens and
      the characteristic and rapidly progressing nature of the periodontal disease in
      these patients.

PMID- 16887571
TI  - Changes of serum and tissue amoxicillin levels following chlorpromazine
      administration in rats.
AB  - Patients under treatment with chlorpromazine (CPZ) may need antibacterial
      administration. Amoxicillin is the most widely used antibacterial agent in dental
      infections. The aim of this study was to investigate the possible interactions
      between amoxicillin and CPZ and the eventual changes in amoxicillin levels using
      an experimental model in rats. Thirty male Wistar rats weighing 200-260 g were
      used for this study. They were divided into three groups: group A taking 15 mg/kg
      amoxicillin every 8 h for 4 days; group B taking amoxicillin as group A, and 1.07
      mg/kg CPZ every 8 h for 4 days; and group C taking only CPZ in the same dose as
      group B. Drugs were given per os for 4 days, using a special catheter. The rats
      were sacrificed 2 h after the last dose. Antibacterial levels were estimated in
      blood serum, jaw bones, tongue and liver. An increase in the level of amoxicillin
      in serum as well as in tissues was observed in group B. No significant
      antibacterial activity of CPZ was detected. The increase in amoxicillin
      concentration in serum and jaws of group B was statistically significant in
      relation to group A.

PMID- 16887572
TI  - Bilophila wadsworthiain brain abscess: case report.
AB  - A case of a patient with a 20-year history of chronic otitis media complicated by
      cholesteatoma and brain abscess is described. A CT scan with contrast material
      showed three abscess cavities in the right cerebellar hemisphere. A culture from
      a specimen of the cholesteatoma yielded a significant amount of growth of
      Bilophila wadsworthia, Bacteroides fragilis and Prevotella oris and a moderate
      growth of alpha-streptococci and Staphylococcus simulans. From the pus of the
      brain abscess we also isolated numerous Bilophila wadsworthia, Bacteroides
      fragilis and Prevotella oris and some Prevotella buccae and Peptostreptococcus
      anaerobius. No aerobes were present. The patient underwent a craniotomy and the
      biggest abscess was removed together with the capsule. The antimicrobial therapy
      included penicillin plus metronidazole and later augmentin. The result of the
      treatment was a complete cure and total recovery of the patient. This is the
      first documentation of isolation of B. wadsworthia in chronic otitis media and in
      brain abscess.

PMID- 16887573
TI  - Anaerobes in waters.
AB  - The classification of anaerobic bacteria in the aquatic environment with regard
      to their ability to survive in extreme environments (such as high or low
      temperatures, high salinity and pH) as well as the pathogenicity of Clostridia
      are presented briefly in this article. The importance of anaerobic bacteria in
      environmental pollution and several types of corrosion is discussed. The
      usefulness of anaerobic bacteria as pollution indicators of pollution in the
      aquatic environment and the methods used for their isolation, enumeration and
      identification are also presented.

PMID- 16887574
TI  - Anaerobic infections of the soft tissue and bones.
AB  - Severe soft tissue infections, usually necrotizing, are associated with a
      mortality of 40-60% and with amputations where the bones and joints are involved.
      The anaerobic bacteria associated with these infections are usually present in
      patients with underlying predisposing conditions (diabetes, vascular problems,
      immunosuppression). They are in the majority polymicrobial, endogenous or
      exogenous. There are many clinical and laboratory characteristics to establish
      the diagnosis of the different forms of these infections. Treatment of
      necrotizing soft tissue and bone infections requires early and aggressive
      surgical debridment. Timing of diagnosis and surgery influence essentially the
      outcome. Colostomy can be helpful in cases of perineal involvement. Antibiotic
      covering (broad spectrum) is mandatory as well as the systemic support of the
      patient.

PMID- 16887576
TI  - Protective activity of different immunosera against Clostridium chauvoei.
AB  - The protective activity of several antiserum preparations against C. chauvoei
      strain 5078 challenge is studied. Immunosera were obtained from the following
      antigenic preparations from 12 h-old cultures of C. chauvoei at 37 degrees C in
      anaerobic conditions: (1) flagellar suspension (F); (2) cellular extract (CE):
      lyophilised cells (0.5 g) extracted by using veronal buffer, pH = 8.6; (3)
      formaldehyde-treated cell suspension with 0.5% of formol (FC); and (4) heated
      cells boiled for 2 h(OC). Lots of white rabbits were inoculated by i.v. route for
      each immunogenic preparation. The immunosera agglutination titres were: F:1:476,
      CE: 1:13186; FC 1:476 and OC: 1:64. Passive immunisation was carried out by
      injecting by the i.p. route groups of ten mice with 0.5 mL of pooled sera. Mice
      were challenged 6 h later with a spore suspension in CaCl2 2.5% containing 10
      LD50. Both immunised and non-immunised animals were observed for 4 days. Anti-CE
      and anti-FC protected 100% of the animals, while anti-F and anti-OC protected 75%
      and 50%, respectively. Results showed that protective antigens were extracted by
      the veronal buffer, and that heat destroys some of them. Although FC protected
      100% of immunised animals, it has been shown elsewhere that CE presented the same
      protective response in mice when diluted at least 1:500. Results also show that
      flagella contributes in part to the immunogenicity of the strain.

PMID- 16887575
TI  - An investigation of the prevalence of the toxigenic types of Clostridium
      perfringens in horses with anterior enteritis: preliminary results.
AB  - Equine anterior enteritis is an acute syndrome with unknown aetiology, although
      salmonellosis and infection with Clostridium perfringens have both been suggested
      as potential causes. The main aim of this preliminary study was to compare the
      prevalence of toxigenic types of C. perfringens in clinically healthy horses and
      in horses with anterior enteritis. From horses admitted with colic at Phillip
      Leverhulme Large Animal Hospital in 1995-1996, samples of gastric reflux, small
      intestinal contents and faeces were taken for isolation of C. perfringens. Five
      of those horses were admitted as anterior enteritis cases, of which C.
      perfringens was isolated in pure culture in all five horses. Two of the anterior
      enteritis cases from which viable bacterial counts had been performed revealed
      10(6) CFU/g faeces C. perfringens. Samples of gastric reflux and small intestinal
      contents submitted from one of these horses revealed 10(4) CFU/mL and 10(5)
      CFU/mL respectively. The number of C. perfringens observed in the gastric reflux
      was considered significant as the total volume removed was 12 L. The counts
      observed in faeces taken from horses admitted with anterior enteritis, were
      significantly higher than the <10(2) CFU/g faeces observed in faeces from healthy
      horses and horse presenting with colic and with other diagnoses. The major
      toxigenic types of C. perfringens in both healthy and diseased horses are being
      investigated using the polymerase chain reaction (PCR) to amplify target DNA
      sequences of the toxin genes. Primers have been designed from the published DNA
      sequences of the enterotoxin, alpha, beta, epsilon and iota toxin genes. PCR
      products obtained from NCTC strains of C. perfringens have been cloned and the
      sequenced, to verify that the amplicon sequence is correct. Initial typing
      suggests that C. perfringens type A is the predominant toxin type isolated from
      healthy horses and horses with colic with other diagnoses.C. perfringens strains
      isolated from horses with anterior enteritis are of type D.

PMID- 16887577
TI  - Bifidobacteria and human health: regulatory effect of indigenous bifidobacteria
      on Escherichia coli intestinal colonization.
AB  - Bifidobacteria are assumed to exert colonization resistance to enteric pathogens.
      We associated C3H germfree mice with either Bifidobacterium longum or Escherichia
      coli or both strains and studied how they settled in the gut and the lymphoid
      organs as well as their effect on mucus composition. Within 24 hE. coli colonized
      the gut of germfree or B. longum ex-germfree mice. In contrast,B. longum was
      established in the intestine of E. coli ex-germfree mice only 1 month after
      inoculation whereas it colonized the germfree gut within 24 h. Although B. longum
      did not exert colonization resistance to E. coli, the establishing of
      bifidobacteria in the gut partly prevented changes in the E. coli cell wall.
      After colonization of the germfree or B. longum mono-associated mice, E. coli
      lipopolysaccharide exhibited a higher concentration of Kdo and the O-antigen side
      chain disappeared. A reduction in Kdo content was observed within 1 month in E.
      coli-B. longum diassociated mice whereas it remained at a high level in E. coli
      mono-associated mice. Association in a second step with B. longum led to Kdo
      reduction. Changes in E. coli LPS might be related to mucus modification.
      Inoculation of either bacterium led to a slow increase in mucus protein content
      which was however twice as high after E. coli implantation. Inoculation of B.
      longum in a second step led to a reduction in protein content before B. longum
      colonized the intestine at a high level suggesting that the protein concentration
      in the mucus was controlled by the host itself. A new glycoprotein of 200-230 kDa
      detected during the period preceeding colonization seemed to be broken down by B.
      longum. The resulting end product might participate in the restoration of E. coli
      LPS. Finally,B. longum inoculation led to the disappearance of E. coli from
      kidneys, liver, spleen and lung. The organs were cleared of E. coli before B.
      longum highly colonized the intestine suggesting that high intestinal
      colonization by B. longum was not required. Regulation of E. coli invasion seemed
      to depend on the ability of B. longum to stimulate the immune system.

PMID- 16887578
TI  - Cell-free wheys from bifidobacteria fermented milks exert a regulatory effect on
      the intestinal microflora of mice and humans.
AB  - Bacteroides fragilis and clostridia are normally present in the human colon but
      they may exert pathogenic effects when the homeostasis is upset following various
      forms of stress. One approach to preventing gastrointestinal disorders is to use
      bifidobacteria fermented milk. It has been suggested that the efficacy of such a
      product is related to abiotic compounds produced during milk fermentation.
      Experiments reported in this paper attempt to check this theory. Six whey
      retentates were prepared by fermenting cow's milk with six human strains of
      Bifidobacterium breve and acetic and lactic acids were eliminated by
      ultrafiltration. Their ability to reduce intestinal clostridial carriage was
      assessed in C3H mice. Only one whey retentate led to a decrease in clostridia,
      bacilli, B. fragilis and fecal pH and to an increase in bifidobacteria. Assays in
      ten human volunteers resulted in similar changes in fecal flora and fecal pH
      within 7 days of whey retentate intake (30 mL/day). No antibiotic-like effect was
      demonstrated in vitro. Compounds involved in microflora regulation were located
      in two ultrafiltrated fractions (30-100 and 100-300 kDa). Both fractions
      contained mainly low molecular weight glycoproteins (20-40 kDa) and two high
      molecular weight glycoproteins (121, 211 kDa) that were almost undetectable in
      the inactive 10-30 kDa fraction.

PMID- 16887579
TI  - Influence of antibiotics on some intestinal microflora associated
      characteristics.
AB  - Intestinal functions related to the presence of microbes in host organisms are
      normally heavily influenced by administration of antimicrobial drugs. We have
      investigated the effect of several antibiotics in man and rat, on some MACs
      (Microflora Associated Characteristics). A MAC is defined as the recording of any
      anatomical structure, biochemical or physiological function in the host organism
      which is influenced by microflora. When functional, active microbes are absent as
      in germfree animals, healthy newborns, or in relation to antimicrobial therapies,
      a MAC defined as a GAC (Germfree Animal Characteristic). Faecal samples have been
      collected prior to, during and up to several weeks after the antimicrobial
      administration in order to investigate different MAC/GAC patterns. Microbial
      conversion of cholesterol to coprostanol, bilirubin to urobilinogen and 7-alpha
      dehydroxylation of cholic acid have been investigated to evaluate
      hepatic/intestinal co-functions, and degradation of intestinal mucin in order to
      evaluate the integrity in the intestinal mucosa. Furthermore, degradation of the
      dietary derived beta-aspartylglycine, the level of faecal trypsin and production
      of short chain fatty acids were investigated to evaluate dietary/intestinal co
      functions. It is concluded that each antimicrobial drug creates its own profile,
      both with regard to duration and function.

PMID- 16887581
TI  - Subgingival microflora in smokers with early onset periodontitis.
AB  - Cigarette smoking is a potent risk factor which has recently been associated with
      periodontal disease progression. The objective of this study was to detect the
      microbial profile of early onset periodontitis in smokers and compare it to that
      of non-smokers. The study population consisted of 50 systemically healthy
      individuals aged 25 to 38 years, exhibiting early onset periodontitis. 25
      patients were smokers (> 20 cigarettes/day) and 25 non-smokers. Two pooled
      bacterial samples comprised of four periodontal sites with probing depth > 5 mm
      each, were collected from each individual. The samples were cultured aerobically
      and anaerobically for bacterial isolation using selective and non-selective
      media. Isolates were characterized to species level by conventional biochemical
      tests and various identification kits. The differences in bacterial counts using
      the Mann Whitney U test were statistically significant for Staphylococcus aureus,
      Campylobacter concisus, Eikenella corrodens, Escherichia coli, Bacteroides
      forsythus, Bacteroides gracilis, Campylobacter rectus, Porphyromonas gingivalis,
      Selenomonas sputigena and Candida albicans in smokers. Statistically significant
      differences for Peptostreptococcus micros, Actinomyces naeslundii, Eubacterium
      lentum and Capnocytophaga gingivalis were detected in non-smokers. The isolation
      of bacteria belonging to the exogenous flora like E. coli, C. albicans and S.
      aureus in smokers microflora underscores the importance of the host which is
      adversely affected by cigarette smoking.

PMID- 16887580
TI  - Postanginal sepsis syndrome with metastatic lung abscess in a young man.
AB  - A postanginal Sepsis Syndrome with metastatic lung abscess caused by
      Fusobacterium necrophorumin a 25-year-old previously healthy man is described.
      The incomplete and ineffective antibiotic treatment at onset of angina ended
      progressively in septicaemia and metastatic infections in a 3-week time period.
      The early parenteral use of Metronidazole based only on the clinical picture, the
      Gram stain findings and the strict anaerobic feature of the blood isolate in
      parallel with the long-term antibiotic treatment were possibly the main reasons
      for the good outcome of this serious infection.

PMID- 16887583
TI  - One-stage full-mouth disinfection to overcome intra-oral transmission of
      periodontopathogens.
AB  - The oral cavity offers a range of different niches where periodontopathogens can
      adhere and survive (e.g. the mucosa, the tongue, the tonsils, the saliva and all
      intra-oral hard surfaces such as teeth, dentures, oral implants). Transmission of
      bacteria from one niche to another is likely to occur. Recent studies, for
      example, illustrated that initially sterile abutments of oral implants were
      rapidly colonized by bacteria from the subgingival environment around teeth. This
      transmission of bacteria can occur spontaneously via the saliva, or by means of
      oral hygiene aids and/or dental instruments. Such an intra-oral transmission, if
      it occurs at a high speed, could jeopardize the outcome of periodontal therapy.
      To overcome a bacterial transmission, a 'one-stage full-mouth disinfection' was
      recently introduced for the treatment of periodontal infections. This new
      treatment strategy resulted in significant clinical and microbiological
      improvements when compared with the standard sequential treatment.

PMID- 16887582
TI  - Anaerobic bacteria in clinical infections.
AB  - The findings of 275 cultures from routine clinical specimens obtained from
      lesions in different sites of body, during a period of 11 months, are presented.
      The clinical specimens were obtained from surgical wounds, abdominal infections,
      orthopaedic operations, biliary tract infections and pleuropulmonary infections.
      The total number of positive cultures including both aerobes and anaerobes was
      203 out of 275 (73.8%). Of the 38 cultures positive for anaerobes, 29 (76.3%)
      grew both aerobic and anaerobic bacteria, while in nine (23.7%) cultures only
      anaerobes were found. A total of 42 strains of anaerobic bacteria were isolated.
      The majority of them were found in clinical specimens obtained from abdominal
      infections (62%), while a low percentage (3.6%) was found in specimens from
      orthopaedic operations. Strains belonging to the genus Bacteroides were the most
      frequently isolated anaerobes, accounting for 35.7% of the total, followed by
      Clostridia 28.5%, Peptostreptococci 23.8% and Prevotella 12%.

PMID- 16887584
TI  - Distribution of Clostridium perfringens in polluted lake environments.
AB  - Many of the directives that relate to the prevention of pollution or the
      improvement of fresh water also relate to lake waters since lake waters
      ultimately inherit much of the pollution that enters into fresh water. In order
      to determine the influence of the water depth on Clostridium perfringens, we
      utilised a new medium, lactose-sulfite (LS) broth, suggested for rapid
      enumeration and identification of C. perfringens. Duplicate samples were
      collected at each one of the following sites of the polluted station: surface, 60
      cm, 90 cm and bottom (1.18 cm). Membrane filtration equipment was used. All
      samples were alternatively passed through two membrane filters, the first (20-25
      microm pore size) was used for retention of the abundant phytoplankton and the
      second (porosity 0.45 microm) for C. perfringens. Membranes were placed into the
      first tube of ten-fold dilutions from 10(1) to 10(4) and incubated aerobically in
      a waterbath at 46 degrees C for 24 h. The numbers of C. perfringens fluctuated
      depending on the water depth. Vegetative forms were found only in the bottom
      sampling; they were never found in surface, 60 cm and 90 cm sampling sites.
      Sporulated forms were found in all sampling sites with the exception of the
      surface sampling. Clostridium perfringens as an anaerobic bacterium never
      occurred in the surface waters in vegetative or spore forms, even if the waters
      were extremely polluted by domestic or industrial activities. Vegetative forms
      occurred only in the bottom samples but spore forms which are more resistant to
      various environmental effects occurred in all depths except for the surface.

PMID- 16887585
TI  - The intestinal microflora during the first weeks of life.
AB  - Bacterial colonization of the neonatal gastrointestinal tract begins during birth
      when the neonate comes into contact with the maternal cervical and vaginal flora.
      In infants delivered by Caesarean section, bacteria colonizing the neonate
      gastrointestinal tract are provided by the environment. The first bacteria
      encountered in the majority of healthy infants, are facultative anaerobes, which
      remain predominant during the first 2 weeks of life. Among them, Staphylococcus,
      Enterobacteriaceae and Streptococcus were the genera most commonly isolated from
      the newborn faecal flora at birth. Facultative anaerobic bacteria are followed
      closely by Bifidobacterium sp. Clostridium perfringens is present within 2 days
      with an increase incidence in newborns delivered by a Caesarean section.
      Clostridium perfringens seems to be the precursor for installation of other
      anaerobic putrefactive bacteria, as Bacteroides and other Clostridium sp. The
      impact of Caesarean section and the period and quality of hospitalization are
      mainly implicated in changes of the normal newborn flora. Feeding seems to
      modulate the colonization pattern. In humans, breast milk plays a role in passive
      immunization of the neonatal intestine, and contains factors that promote the
      growth of Bifidobacterium bifidum in the intestinal flora. Formula feeding seems
      to promote implantation and persistence of Clostridium perfringens, and clearly
      enhances intestinal colonization of C. difficile in newborns.

PMID- 16887586
TI  - What is currently known about the molecular mechanisms of colonisation
      resistance.
AB  - Anaerobes are the main bacteria which inhabit the digestive tract. They have
      adapted their development to many environmental factors such as host secretions,
      corresponding to control mechanisms which allow a relative stability of
      microflora in healthy humans. These control mechanisms include the control of
      endogenous and exogenous bacterial populations which corresponds to bacterial
      antagonism occurring in the digestive tract of mammals and represents one of its
      main functions. The main antagonism to study is colonisation resistance since
      this function of the gut microflora is responsible for the prevention of many
      intestinal diseases. However, only a few things are currently known about this
      function and the main questions which need attention are: (1) which bacteria are
      responsible for colonisation resistance? and (2) what are the molecular
      mechanisms involved in such a function? In order to answer these questions, we
      need to study simplified models based on gnotobiotic animals. Two models are
      currently being studied in France. One corresponds to the colonisation resistance
      of C. perfringens which seems to be linked to the in vivo secretions of an
      antimicrobial substance by a Ruminococcus species. The other corresponds to the
      colonisation resistance of C. difficile whose mechanisms are different and seem
      to be linked to an interaction between mucin and microflora.

PMID- 16887587
TI  - Fermented products with probiotic qualities.
AB  - For several centuries, fermented products derived from plant or animal materials
      have been an acceptable and essential part of the diet in most parts of the
      world. Health benefits have also often been associated with them. Probiotics can
      be defined as fermented food containing specific live microorganisms or a live
      microbial food or feed supplement, which beneficially effects the human or the
      host animal by improving its intestinal microbial balance. Nearly all probiotics
      currently on the market contain Lactobacilli, Streptococci, Enterococci or
      Bifidobacteria. In contrast to Japan, where freeze-dried microorganisms are
      consumed by a substantial part of the human population, in Europe, probiotic
      action towards humans are only claimed for certain fermented dairy products (e.g.
      yoghurts). Those species that have been extensively studied so far, with several
      experimental trials on man, are the two yoghurt bacteria Streptocaccus
      thermophilus and Lactobacillus bulgaricus, L. casei and Bifidobacteria. L.
      acidophilus has also received important scientific interest, however, only a few
      human studies have been carried out. From the technological point of view a good
      probiotic should be stable and viable for long periods under storage, should be
      able to survive the low pH levels of the stomach, be able to colonise the
      epithelium of the gastro-intestinal tract of the host, should not be pathogenic
      and, last but not least, must be capable of exerting a growth promoting effect or
      a resistance to infectious diseases. The beneficial effects of probiotics are
      mainly contributed to a direct antagonistic effect against specific groups of
      microorganisms (Enteropathogenes), by an effect on the metabolism in the gut or
      by a stimulation of systemic or mucosal immunity. We will present major proven
      health benefits of milks fermented with those bacterial species and discuss,
      where possible, the impact of the specific selection and utilisation of
      particular strains.

PMID- 16887588
TI  - Rapid Identification of Clostridium perfringens in animal feedstuffs.
AB  - Clostridium perfringens is a common contaminant of grains and meals used for
      animal feeding and its presence in feedstuffs has been implicated in outbreaks of
      foodborne poisoning in farm animals. In order to evaluate a new rapid procedure
      for C. perfringens isolation and identification, we examined qualitatively 120
      duplicate samples of feedstuffs used for farm animal and poultry feeding, using
      the Lactose-Sulfite broth (LS) proposed for rapid C. perfringens detection and
      the conventional Cooked Meat Medium (CMM). The results suggest that LS medium is
      fairly successful in the detection of C. perfringens vegetative cells and spores,
      despite the presence of the bacterial and fungal flora normally found in animal
      feedstuffs.

PMID- 16887589
TI  - Fournier's Gangrene: a clinical and bacteriological study.
AB  - Bacteriological studies were conducted in patients presenting with Fournier's
      Gangrene (FG) in our Department during a period of 11 years. These studies showed
      high numbers of anaerobes (96%) and the ratio of aerobes to anaerobes was
      reported to be 1.4: 3.2. Among the anaerobes,Peptostreptococci, Bacteroides and
      Prevotella were more frequently isolated. The predominant facultative aerobic
      microorganisms were Streptococci and Escherichia coli. Clinical investigation
      showed necrotic cellulitis and fasciitis of the scrotum due to mixed aerobic
      anaerobic infection. Patients with complicated paraproctitis and periurethral
      abscesses and urinary phlegmones who also presented with symptoms of FG were
      treated during this same period. Microbiological studies gave similar results and
      clinical studies showed that the process had spread to the scrotum. The question
      was then raised whether FG should be diagnosed as an independent nosological
      entity in cases where the underlying cause of the disease was obscure or if FG
      should be the result of different pathological processes which occurred within
      the scrotal surfaces. In other cases, FG is secondary and occurred after reaching
      the scrotum per continuitatem.

PMID- 16887590
TI  - Alpha-toxin production by Clostridium septicum at different culture conditions.
AB  - Clostridium septicum is responsible for a number of diseases, the most serious of
      which are a frequently fatal non-traumatic gas gangrene in man and braxy
      malignant oedema and blackquarter in farm animals. Immunity to these diseases is
      mediated mainly by antitoxin raised against C. septicum alpha toxin, which has
      hemolytic, lethal and necrotizing activities. Clostridium septicum produces
      lethal antigen only in low titre and in a variable way. In addition, the
      immunogenicity of native toxic filtrates is weak, which results in poor antibody
      response in animals. The aim of this work was to determine the best culture
      conditions for obtention of the protective antigen. To do this, the presence of
      the alpha toxin was identified in culture filtrates by means of SDS
      polyacrylamide gel electrophoresis (SDS-PAGE) under different culture conditions.
      The strain used was C. septicum 3606. The cultures were performed in anaerobic
      conditions at 37 degrees C. Two systems were employed: (a) batch (0.5% initial
      glucose concentration); and (b) batch with partial feeding of the carbon source
      (0.1% glucose concentration) at controlled pH. The hemolytic activity of
      supernatants was determined using human erythrocytes, and the final biomass
      concentration was estimated by dry weight determination. The proteins present in
      supernatants were concentrated by ultrafiltration and identified in 10% SDS
      polyacrylamide gels. With partial feeding of the carbon source the final biomass
      (2.22 g/L) was three times higher than the amount reached in batch system (0.70
      g/L), however, no difference was found in the hemolytic activity (16 HU50/mL)
      showing no correlations between cell growth and hemolytic activity of the
      supernatants. Electrophoresis of filtrate cultures obtained with partial feeding
      of the carbon source allowed us to identify several bands, two of them
      corresponded to non-active alpha-protoxin (46 kDa) and the active toxin (42 kDa)
      and the aggregate of the active toxin at the seeding line. On the other hand, the
      ultrafiltrate from batch system showed less number of bands and the 46 kDa band
      was much weaker, suggesting a lower toxin production in this system. It becomes
      important to determine culture conditions and correlate with extracellular
      protein presence to optimize C. septicum antigen protector production.

PMID- 16887591
TI  - Bacterioides fragilis: production and sensitivity to bacteriocins.
AB  - Bacteriocin production and sensitivity to bacteriocins have been successfully
      applied as an epidemiological tool in several species of bacteria. However,
      little work has been carried out on the bacteriocins produced by Bacteroides
      fragilis, which is the most frequently isolated anaerobe species from clinical
      specimens. Thirty two clinical isolates of B. fragilis grown anaerobically on a
      0.22 microm membrane filter spotted on an agar plate, were tested for bacteriocin
      production and used in a screen for bacteriocin sensitivity. Sensitivity to at
      least one bacteriocin was found in 94% of the strains, 62.5% were sensitive to
      two bacteriocins, whereas 34.4% were sensitive to three or more and finally one
      strain was found sensitive to 17 bacteriocins. Of the strains studied, 94%
      inhibited at least one strain, 66% inhibited two strains, and 30% inhibited at
      least three strains or more. Finally, one strain was extremely active by
      inhibiting the growth of 17 strains. Bacteriocin types are characterised by
      geographic variation, and their epidemiological investigation by a simple method
      could be promoted.

PMID- 16887592
TI  - Bacteriologic and therapeutic considerations in intra-abdominal surgical
      infections.
AB  - The most important factor in the treatment of intra-abdominal infections are
      early diagnosis and prompt surgical intervention while antibiotics play a
      secondary role. The goals of surgical procedures should be to stop peritoneal
      contamination, to debride necrotic tissue, to remove debris and foreign bodies
      and to drain any pus collection. Antibiotics should be initiated before surgery
      and they must encompass both colonic aerobes and anaerobes including Bacteroides
      fragilis group but not necessary Enterococcus sp. Antibacterial agents with pure
      activity against anaerobes include chloramphenicol, clindamycin and the
      nitroimidazoles while ampicillin/sulbactam, amoxicillin/clavulanate,
      ticarcillin/clavulanate, cefoxitin, cefotetan, ceftizoxime imipenem/cilastatin,
      meropenem and some advanced quinolones like sparfloxacin, represent a single drug
      to cover both aerobic and anaerobic microflora. Although almost all clinical
      trials usually result in a 90% efficacy rate, the final outcome is dependant on
      the stage of the infection (early versus late), sepsis score, underlying diseases
      and the applied surgical procedures. On the other hand the choice of
      antibiotic(s) must be influenced by its toxicity, profiles local nosocomial
      susceptibility patterns, resistance inducing ability and price.

PMID- 16887593
TI  - Robert E. Hungate: pioneer of anaerobic microbial ecology.

PMID- 16887594
TI  - Recovery of Bilophila wadsworthiafrom Clinical Specimens in Italy.
AB  - This report is the first survey in Italy to evaluate the incidence of recovery of
      Bilophila wadsworthia in clinical situations. The survey was carried out at the
      departments of Microbiology in two Northern Italian hospitals over a one-year
      period. Tests for B. wadsworthia were carried out on a range of specimens from
      different body sites, when etiology by anaerobes was suspected. Out of a total of
      350 samples examined, 67% were positive in bacteriological tests. Mixed anaerobic
      infections were detected in 53 specimens, corresponding to 23% of all cases.
      Strains of B. wadsworthia were isolated from 12 samples, equivalent to 5% and 22%
      of total and mixed/anaerobic infections, respectively. Bilophila wadsworthia was
      always isolated in mixed infections, mainly from the large intestine (67% of
      cases). The infectious process of B. wadsworthia was often complicated by abscess
      formation, regardless of body site. Interestingly, a strain was isolated from one
      case of bacteremia. The microorganisms most frequently isolated with B.
      wadsworthia were Escherichia coli for facultative species (38%), and Bacteroides
      fragilis, from anaerobic isolates (25%). Production of beta-lactamases by B.
      wadsworthia isolates was found in ten strains (83%), which appeared to be
      penicillin G resistant at concentration equal to or greater than the break-point
      (4 microg/mL). Epidemiological and clinical data from this and previous studies
      point to the involvement of B. wadsworthia in mixed infections. To assess the
      specific contribution of the species to the disease, studies of pathogenetic
      factors are to be considered in parallel. Nonetheless, production of beta
      lactamases by most B. wadsworthia isolates could easily interfere with the
      therapeutical approach to infections involving the new species. The addition of a
      selective medium to culture specimens from the abdominal cavity should be
      considered in order to detect the presence of B. wadsworthia.

PMID- 16887595
TI  - Broth disk elution method for anaerobic bacteria: a collaborative study to assess
      its reliability for clinical purposes.
AB  - A collaborative study involving seven laboratories was undertaken to evaluate the
      reproducibility and the reliability of the broth disk elution test against
      anaerobic bacteria by comparing with the reference agar dilution method. A two
      breakpoint broth test was also evaluated. Assays were performed using the same
      testing conditions (i.e. medium, temperature, atmosphere and incubation time).
      One hundred Gram-negative and Gram-positive clinical isolates were initially
      studied. Overall agreement of 98.5% and 97.5%, were found for disk elution and
      the two breakpoint tests, respectively. In order to assess the reliability of the
      disk elution test, two different lots (LOT1 and LOT2) of disks of piperacillin
      and clindamycin were selected, to obtain two final concentrations after dilution
      (10 and 60 mg/mL; 1 and 4 mg/mL, respectively). Two hundred and eighty assays
      were performed against one strain of both Bacteroides fragilis(piperacillin MIC,
      8.0 mg/mL; clindamycin MIC, <0.5 mg/mL) and Bacteroides
      thetaiotaomicron(piperacillin MIC, 16.0 mg/mL; clindamycin MIC, <0.5 mg/mL). With
      LOT 1, considering both species and both antibiotics, the agreement among six
      laboratories ranged from 85% to 100% (P > 0.05) with the higher concentration.
      Overall agreement among all laboratories was 91%. No optimal agreement (>90%) for
      clindamycin-Bacteroides thetaiotaomicron using the LOT1 (77%) was found. Since
      this finding was not observed with LOT2 (100% agreement), discrepancies were
      attributed to variation between lots. Overall agreement with LOT2 was 100% for
      all centres. The present study indicates that the broth disk elution method
      proved to be a reliable and suitable alternative for routine susceptibility
      testing for anaerobic bacteria, as a resistance screening method for clinical
      purposes.

PMID- 16887596
TI  - Distinctive outer membrane protein and lipopolysaccharide composition of
      Bacteroides fragilis strains that produce metallo-beta-lactamase.
AB  - The outer membrane protein and lipopolysaccharide compositions of Bacteroides
      fragilis strains which produced metallo-beta-lactamase were shown to be different
      from those of fully sensitive random clinical isolates of Bacteroides fragilis in
      which metallo-beta-lactamase production was not detected. This may reflect
      differences in the permeability barrier and provides phenotypic evidence that
      Bacteroides fragilis which produce metallo-beta-lactamase may belong to a
      separate biotype. Outer membrane profiles may provide a rapid means of
      identifying these problem strains.

PMID- 16887597
TI  - Ribotyping of bacteria from root canal and blood of patients receiving endodontic
      therapy.
AB  - DNA restriction patterns and corresponding ribotypes of 26 bacterial isolates
      (Propionibacterium acnes, Peptostreptococcus prevotii, Fusobacterium nucleatum,
      Prevotella intermedia, Prevotella nigrescens, Actinomyces israelii, Streptococcus
      intermedius, and Streptococcus sanguis) recovered from patients with infected
      root canals and their peripheral blood, collected during and after endodontic
      therapy, were examined. Eleven additional reference strains including type
      strains were also examined. Purified DNA was digested with BglI,EcoRI, and
      HindIII. Hybridization was carried out with a digoxigenin-labeled cDNA probe
      obtained by reverse transcription of Escherichia coli 16S + 23S rRNA. Ribotypes
      of the bacteria recovered from root canal and blood showed identical
      characteristics within the patients, and differed between the patients. The
      results were confirmed when the similarity coefficient (S(AB)) of the ribotypes
      from the isolates were assessed by the Dendron computer-assisted system. These
      results suggested that the bacteria isolated from the blood originated from the
      root canal.

PMID- 16887598
TI  - Typing of Clostridium perfringens strains by use of Random Amplified Polymorphic
      DNA (RAPD) system in comparison with zymotyping.
AB  - The definition of strain clonality postulates that strains showed identical
      phenotypic and genetic traits are likely to descend from a common ancestor even
      if they were isolated from different sources and locations. Regarding this
      definition, non-epidemiologically linked strains might be clonal strains. To
      overcome this ambiguity, the discriminatory capability of RAPD typing was
      assessed firstly on eight Clostridium perfringens strains proven to be
      chromosomally different with one being the mutant of another one. Thirteen
      primers were tested but only two were able to differentiate seven of the eight
      strains. With none of the used primers it was possible to differentiate the
      parental strain and its mutant harboring an insertion of 180 kb. The four most
      discriminant primers were retained to determine the RAPD fingerprints of a
      further 20 previously zymotyped strains from which seventeen were unrelated. To
      compare the two typing systems, the zymotype of the eight chromosomally different
      strains was determined. Thus, the discriminatory index was calculated on the
      basis of 25 unrelated C. perfringens strains. This was 0.97 with RAPD typing and
      0.99 with zymotyping. From these results we conclude that the RAPD typing which
      is less fastidious than zymotyping can be used as an epidemiological marker for
      C. perfringens.

PMID- 16887599
TI  - Peptidase activity of human colonic bacteria.
AB  - Aminopeptidase activities of mixed faecal suspensions from four human donors and
      12 of the most numerous species of human colonic bacteria were measured using
      alanine oligopeptides and various dipeptidyl- and amino acyl-arylamidase
      substrates. The pattern of hydrolysis of Ala(4)and Ala(5)in faecal suspensions,
      whereby Ala(2)was the first breakdown product, suggested that the main mechanism
      of peptide hydrolysis was dipeptidyl peptidase. Dipeptidyl p-nitroanilides and 4
      methoxynaphthylamides were broken down more rapidly than amino acyl derivatives
      in three out of four individuals tested, consistent with this conclusion. The
      predominant Bacteroides spp. of the intestine also had greater dipeptidyl
      peptidase activity than amino acyl aminopeptidase activity, while
      Bifidobacterium, Clostridium, Enterococcus and Propionibacterium spp. had a more
      variable pattern of peptidase activities. Thus, peptide hydrolysis in the human
      intestine, as in the rumen, appears to be mainly a two-stage process which is
      initiated by dipeptidyl peptidases present in the most numerous Bacteriodes spp.

PMID- 16887600
TI  - Molecular cloning, nucleotide sequencing, and expression of genes encoding
      alcohol dehydrogenases from the thermophile Thermoanaerobacter brockii and the
      mesophile Clostridium beijerinckii.
AB  - Proteins play a pivotal role in thermophily. Comparing the molecular properties
      of homologous proteins from thermophilic and mesophilic bacteria is important for
      understanding the mechanisms of microbial adaptation to extreme environments. The
      thermophile Thermoanaerobacter (Thermoanaerobium) brockii and the mesophile
      Clostridium beijerinckii contain an NADP(H)-linked, zinc-containing secondary
      alcohol dehydrogenase (TBADH and CBADH) showing a similarly broad substrate
      range. The structural genes encoding the TBADH and the CBADH were cloned,
      sequenced, and highly expressed in Escherichia coli. The coding sequences of the
      TB adh and the CB adh genes are, respectively, 1056 and 1053 nucleotides long.
      The TB adh gene encoded an amino acid sequence identical to that of the purified
      TBADH. Alignment of the deduced amino acid sequences of the TB and CB adh genes
      showed a 76% identity and a 86% similarity, and the two genes had a similar
      preference for codons with A or T in the third position. Multiple sequence
      alignment of ADHs from different sources revealed that two (Cys-46 and His-67) of
      the three ligands for the catalytic Zn atom of the horse-liver ADH are preserved
      in TBADH and CBADH. Both the TBADH and CBADH were homotetramers. The substrate
      specificities and thermostabilities of the TBADH and CBADH expressed inE. coli
      were identical to those of the enzymes isolated from T. brockii and C.
      beijerinckii, respectively. A comparison of the amino acid composition of the two
      ADHs suggests that the presence of eight additional proline residues in TBADH
      than in CBADH and the exchange of hydrophilic and large hydrophobic residues in
      CBADH for the small hydrophobic amino acids Pro, Ala, and Val in TBADH might
      contribute to the higher thermostability of the T. brockii enzyme.

PMID- 16887601
TI  - RAPD fingerprinting for the distinction of Prevotella intermedia sensu stricto
      from Prevotella nigrescens.
AB  - A collection of 70 oral strains including reference strains and clinical isolates
      identified as Prevotella intermedia sensu lato was constituted to cover a large
      clinical and geographical diversity. Electrophoresis of the enzyme malate
      dehydrogenase allowed the identification of the 70 study strains as Prevotella
      intermedia sensu stricto (n= 36), Prevotella nigrescens (n= 31) and three
      unclassified strains. By using four primers, DNA fingerprints were generated from
      20 strains as random amplified polymorphic DNA (RAPD). Matching co-migrating
      amplicon positions by pairwise comparison allowed the clustering of the
      fingerprints as two groups coincident with the P. intermedia/P. nigrescens
      assignment by enzyme electrophoresis of malate dehydrogenase. Our data suggest
      that isolates identified asP. intermedia sensu lato by conventional criteria can
      be speciated asP. intermedia sensu stricto or P. nigrescens by RAPD
      fingerprinting.

PMID- 16887602
TI  - Nitrate and nitrite utilization in sulfate-reducing bacteria.

PMID- 16887603
TI  - Marvin P. Bryant and bacteria in methanogenic ecosystems.

PMID- 16887604
TI  - Identification of Bacteroides fragilis by co-agglutination, using a specific
      monoclonal antibody.
AB  - A monoclonal antibody, mAbC3 (IgG(2b)), specific for the Bacteroides fragilis
      lipopolysaccharide (LPS) was produced and found to react with a common epitope in
      most strains within the species. mAbC3 was adsorbed to Staphylococcus aureus
      Cowan I strain and used in a co-agglutination assay for identification of B.
      fragilis. Almost 98% of the B. fragilis strains were positive in co
      agglutination. Among the 283 non-B. fragilis only two strains showed false
      positive reaction. These results show that the mAbC3 has a high specificity and
      can be used for the rapid identification of the B. fragilis species.

PMID- 16887605
TI  - In vitro activity of linezolid and eperezolid, two novel oxazolidinone
      antimicrobial agents, against anaerobic bacteria.
AB  - Linezolid (formerly U-100766) and eperezolid (formerly U-100592) are novel
      oxazolidinone antimicrobial agents that are active against multi-drug-resistant
      staphylococci, streptococci, enterococci, corynebacteria, and mycobacteria.
      Preliminary studies also demonstrated that the compounds inhibited some test
      strains of anaerobic bacteria. Therefore, we extended the in vitro evaluation of
      these agents to include a total of 54 different anaerobic species. Minimal
      inhibitory concentration (MIC) values were determined using a standard agar
      dilution method for 143 anaerobic bacterial isolates. Eperezolid and linezolid
      demonstrated potent activity against the anaerobic Gram-positive organisms with
      most MIC values in the range of 0.25-4 microg/mL. Viridans streptococci
      demonstrated MICs of 1-2 microg/mL; Peptostreptococcus species and
      Propionibacterium species were inhibited by </=0.25-1 microg/mL. Clostridial
      species were generally susceptible to the oxazolidinones (MICs of </=0.25-8
      microg/mL); however, seven strains of Clostridium difficile with linezolid MICs
      of 16 microg/mL or greater were detected. Against the anaerobic Gram-negative
      organisms, linezolid was more potent than eperezolid, especially for Bacteroides
      species. Linezolid inhibited most bacteroides in the range of 2-8 microg/mL,
      while eperezolid was generally two- to eight-fold less active. Linezolid and
      eperezolid both demonstrated potent activity against Fusobacterium
      species,Mobiluncus species,Prevotella intermedia, and Porphyromonas
      asaccharolytica (MICs of </=0.25-0.5 microg/mL). Overall, the oxazolidinones
      demonstrated a significant level of activity against a number of clinically
      important anaerobic bacterial species. Linezolid may potentially provide a
      broader spectrum of anaerobic coverage than eperezolid due to its greater
      activity against Bacteroides species.

PMID- 16887606
TI  - H2/CO2 metabolism in acetogenic bacteria isolated from the human colon.
AB  - The present work reports on autotrophic metabolism in four H2/CO2-utilizing
      acetogenic bacteria isolated from the human colon (two Clostridium species, one
      Streptococcus species, and Ruminococcus hydrogenotrophicus). H2/CO2-utilization
      by these human acetogenic strains occurred during both exponential and stationary
      phases of growth. Acetate was the major metabolite produced by all isolates
      following the stoichiometric equation of reductive acetogenesis. Furthermore, the
      ability of these acetogenic bacteria to incorporate 13CO2 into acetate in the
      presence of H2 in the gas phase demonstrated the utilization of the reductive
      pathway of acetate formation from a one-carbon compound. Energy conservation
      during the autotrophic metabolism in colonic acetogens might involve sodium- or
      proton-chemiosmotic mechanisms. A sodium-dependent ATP generation was only
      demonstrated in one Clostridium species, whereas sodium could be replaced by
      potassium in other strains. The minimal thresholds of hydrogen uptake were
      determined and varied from 1100 to 3680 ppm depending on the acetogenic strain.
      These values appeared higher than those measured for the colonic
      methanogen,Methanobrevibacter smithii.

PMID- 16887607
TI  - Ribotyping of adherent Lactobacillus from weaning pigs: a basis for probiotic
      selection based on diet and gut compartment.
AB  - Dietary inoculates for weaned pigs often include lacobacilli, but the effects of
      age and diet on the ecology of adherent lactobacilli are not well known. Four
      experimental treatments included 16 newborn piglets: a pre-weaning treatment (PW)
      included four pigs that were sacrificed at 28 days of age; a sow treatment (Sow)
      had four pigs that remained with the sow (Sow) from 28 to 38 days of age and were
      sacrificed at 38 days of age; and two treatments in which four pigs each, were
      placed on a corn-soy diet with (CSL), or without (CS) 40% lactose. Adherent
      lactobacilli were isolated from the pars esophagus, ileum, and cecum, and
      characterised phenotypically. A 23S rDNA probe hydrized toEcoRI orPstI digested
      DNA, and a 74.8% cut-off individualize isolates into 36 clusters. The most
      predominant strains found in the Sow, CSL, and CS treatments were the same, but
      different strains predominated in the PW animals. The most predominant strains
      found in the pars esophagus and ileum were the same, but different strains
      predominated in the cecum.

PMID- 16887608
TI  - Dissimilatory amino Acid metabolism in human colonic bacteria.
AB  - The abilities of slurries of human faecal bacteria to ferment 20 different amino
      acids were investigated in batch culture incubations. Ammonia, short chain fatty
      acids, and in some cases, amines, were the principal products of dissimilatory
      metabolism. The types of SCFA produced were dependent on the chemical
      compositions of the test substrates. Thus, acetate and butyrate were formed from
      the acidic amino acid glutamate, while acetate and propionate predominated in
      aspartate fermentations. Breakdown of the basic amino acids lysine and arginine
      was rapid, and yielded butyrate and acetate, and ornithine and citrulline,
      respectively. The major products of histidine deamination were also acetate and
      butyrate. However, fermentation of sulphur-containing amino acids was slow and
      incomplete. Acetate, propionate and butyrate were formed from cysteine, whereas
      the main products of methionine metabolism were propionate and butyrate. The
      simple aliphatic amino acids alanine and glycine were fermented to acetate,
      propionate and butyrate, and acetate and methylamine, respectively. Branched
      chain amino acids were slowly fermented by colonic bacteria, with the main acidic
      products being branched-chain fatty acids one carbon atom shorter than the parent
      amino acid. Low concentrations of amines were also detected in these
      fermentations. Aliphatic-hydroxy amino acids were rapidly deaminated by large
      intestinal microorganisms. Serine was primarily fermented to acetate and
      butyrate, while threonine was mainly metabolised to propionate. Proline was
      poorly utilized by intestinal bacteria, but hydroxyproline was efficiently
      fermented to acetate and propionate. The aromatic amino acids tyrosine,
      phenylalanine and tryptophan were broken down to a range of phenolic and indolic
      compounds.

PMID- 16887609
TI  - Membrane-bound cytochromes in a sulfate-reducing strict anaerobe Desulfovibrio
      vulgaris Miyazaki F.
AB  - Cytoplasmic membranes were isolated from the cells of a sulfate-reducing strict
      anaerobe Desulfovibrio vulgaris Miyazaki F and membrane-bound cytochromes were
      characterized. Redox difference spectra at 77 K revealed the presence of
      cytochromes with the alpha peaks at 552 and 556 nm while CO-binding difference
      spectra showed the presence of o-type cytochrome(s). Partial purification of the
      cytochromes demonstrated that the membranes contain cytochromes c550, c551, c556
      and possibly d1 besides high molecular mass cytochrome c and cytochrome c3. It
      turned out that two kinds of novel CO-binding c-type cytochromes are present in
      the membrane. The membranes and a partially purified fraction showed weak
      ubiquinol-1 oxidase activity but no cytochrome c oxidase activity. Results
      suggest that D. vulgaris does not express the heme-copper terminal oxidase under
      our growth conditions in spite of the presence of the col gene, which is
      homologous to the gene of subunit I of the aa3-type oxidase.

PMID- 16887610
TI  - Determination of immunological homology between cellulosome subunits and cloned
      endoglucanases and xylanase of Clostridium thermocellum.
AB  - Immuno-cross reactivity between the subunits of Clostridium thermocellum
      cellulosome and cloned endogucanases and xylanase from the same bacterium was
      studied using the polyclonal antibodies raised against cloned enzymes. Dot blot
      analysis showed that the cellulosome, S8 and S11 subunits cross-reacted strongly
      with the antibodies of all cloned enzymes tested except that raised against CelC.
      Western blot analysis revealed that S8 and S11 subunits cross-reacted with the
      antibodies of CelA, CelB, CelD, CelG, CelH and XynZ, but the antibodies of CelB
      and CelG were highly specific for S8 and S11 subunits, respectively. Similar
      analysis using dissociated cellulosome showed that the antibodies of all cloned
      enzymes tested cross-reacted with more than one subunit of the cellulosome.
      Antibodies of CelC showed a very low cross-reactivity against all subunits of the
      cellulosome. The results indicate that immunological cross-reactivity studies
      could be useful, not only for demonstrating the similarities between native and
      cloned enzymes, but also for identifying native enzymes using antibodies of
      cloned enzymes.

PMID- 16887611
TI  - Ion exchange in facultative anaerobes: does a proton-potassium pump exist in
      anaerobic Escherichia Coli?

PMID- 16887612
TI  - Degradation and utilization of xylans by the rumen anaerobe Prevotella bryantii
      (formerly P. ruminicola subsp. brevis) B(1)4.
AB  - Freshly harvested whole cells from cultures of P. bryantii B(1)4 grown with oat
      spelt xylan (OSX) as an energy source showed less than 25% of the enzyme activity
      against OSX, and less than 15% of the activity against birchwood xylan (BWX) and
      carboxymethylcellulose, that was detectable in sonicated cell preparations. This
      indicates that much of this hydrolytic activity is either periplasmic, membrane
      associated or intracellular and may be concerned with the processing of
      transported oligosaccharides.P. bryantii B(1)4 cultures were able to utilise up
      to 45% and 51% of the total pentose present in OSX and BWX, respectively, after
      24 h, but could utilize 84% of a water-soluble fraction of BWX. Analysis of the
      xylan left undegraded after incubation with P. bryantii showed that while xylose
      and arabinose were removed to a similar extent, uronic acids were utilized to a
      greater extent than xylose. Predigestion of xylans with two cloned xylanases from
      the cellulolytic rumen anaerobe Ruminococcus flavefaciens gave little increase in
      overall pentose utilization suggesting that external P. bryantii xylanases are as
      effective as the cloned R. flavefaciens enzymes in releasing products that can be
      utilised by P. bryantii cells. The xylanase system of P. bryantiiis able to
      efficiently utilise not only xylo-oligosaccharides but also larger water-soluble
      xylan fragments.

PMID- 16887613
TI  - Effect of Methanobrevibacter sp MF1 inoculation on glycoside hydrolase and
      polysaccharide depolymerase activities, wheat straw degradation and volatile
      fatty acid concentrations in the rumen of gnotobiotically-reared lambs.
AB  - Four naturally born lambs were placed in sterile isolators 24 h after birth
      before the natural establishment of cellulolytic microorganisms and archaea
      methanogens. At the age of 6 weeks they were inoculated with pure cultures of the
      strains FD1 and 007 of Ruminococcus flavefaciens and at the age of 4 months with
      a pure culture of Methanobrevibacter sp. MF1. Following the establishment of MF1,
      the population of R. flavefaciens slightly increased in the rumen of the four
      lambs, there was also an increase in straw degradation, in the activity of some
      glycoside and polysaccharide hydrolases of the adherent microbial populations and
      in the concentration of acetate in ruminal contents.

PMID- 16887614
TI  - Comparison of batch culture growth and fermentation of a poultry Veillonella
      isolate and selected Veillonella species grown in a defined medium.
AB  - The objective of this study was to develop a defined medium for quantitating
      nutritional requirements and fermentation products of a poultry cecal isolate of
      Veillonella and to compare these parameters with representative Veillonella
      species. The poultry isolate is one of 29 organisms from a continuous-flow
      culture that has been shown to be effective against Salmonella colonization in
      broilers. When the Veillonella species were grown in anaerobic batch culture,
      propionate and acetate were the only volatile fatty acids detected. Lactate was
      needed to provide energy for the growth of the Veillonella in the defined medium.
      The poultry isolate had significantly (p< 0.05) higher Y(lactate)(g of dry cell
      weight per mole of lactate utilized) and dry cell weight than the other
      Veillonella species when grown on amino acid supplemented defined media. Cultures
      of the Veillonella species in the defined medium grown with supplemented amino
      acids aspartate, threonine, arginine, and serine indicated that these amino acids
      were metabolized to acetate and propionate. Amino acid analysis on media
      inoculated with either V. atypica or the poultry isolate also indicated that
      these organisms may have different amino acid preferences. For nearly all of the
      amino acid supplemented media combinations the poultry isolate utilized
      significantly (p< 0.05) more threonine and serine whereas V. atypica utilized
      significantly (p< 0.05) more aspartate. The defined medium supported growth of
      all of the Veillonella species tested and should enable further in-depth
      physiological studies to be conducted on the poultry Veillonella studies.

PMID- 16887615
TI  - Anaerobic aquifer transformations of 2,4-dinitrophenol under different terminal
      electron accepting conditions.
AB  - We evaluated the susceptibility of 2,4-dinitrophenol (2,4-DNP) and 2,4
      diaminophenol to anaerobic biodegradation in aquifer slurries. Aquifer
      microorganisms depleted 2,4-DNP at rates of 25, 9 and 0.4 microM/day under
      methanogenic, sulfate-reducing and nitrate-reducing conditions, respectively.
      Rates of abiotic, 2,4-DNP loss in autoclaved control incubations were 7.2, 6.2
      and 0.95 microM/day respectively. Abiotic, 2,4-DNP reduction was especially
      important as the first step in its transformation. 2-Amino-4-nitrophenol was
      produced by this process, but this compound was further metabolized in
      methanogenic and sulfate-reducing aquifer slurries. This partially reduced
      compound persisted in autoclaved controls and in the nitrate-reducing aquifer
      slurries. Aquifer slurries incubated with either 2,4-DNP or 2,4-diaminophenol
      produced methane when incubated with no other electron acceptor suggesting that
      mineralization had occurred under these conditions. In parallel experiments,
      aquifer slurries amended with 2,6-dinitrophenol or picric acid did not produce
      methane at levels above the substrate unamended controls.

PMID- 16887616
TI  - Utilization of serine, leucine, isoleucine, and valine by Thermoanaerobacter
      brockii in the presence of thiosulfate or Methanobacterium sp. as electron
      acceptors.
AB  - Thermoanaerobacter brockii fermented serine to acetate and ethanol. It oxidized
      leucine to isovalerate, isoleucine to 2-methylbutyrate, and valine to isobutyrate
      only in the presence of thiosulfate, or when co-cultured with Methanobacterium
      sp. This oxidative deamination was rendered thermodynamically possible by the
      ability ofT. brockii to reduce thiosulfate to sulfide or the transfer of reducing
      equivalents to the hydrogenotrophic methanogen. The results suggest that T.
      brockii may be of ecological significance in thermal environments in the turnover
      of amino acids, especially with thiosulfate or H(2)-utilizing methanogens are
      present.

PMID- 16887617
TI  - Characterisation of a transposon-induced pleiotropic mutant of Clostridium
      acetobutylicum P262.
AB  - Transposon-induced metronidazole resistance was used as a selection system for
      the isolation of Clostridium acetobutylicum P262 mutants with altered electron
      transport pathways. The metronidazole resistant transconjugant of interest,
      mutant 3R, displayed resistance to DNA damaging agents, UV and bleomycin, and
      harboured a single transposon insertion within a structural gene, designated
      sum(susceptibility to metronidazole). The sum gene encoded a 334 amino-acid
      protein, with 36% identity and 57-58% similarity at the amino acid level to two
      archaebacterial protein sequences which appear to represent a class of
      uncharacterised reductase enzymes. Physiological studies of mutant 3R revealed a
      number of pleiotropic characteristics which included enhanced autolysin activity,
      increased motility, impaired clostridial cell formation, and resistance to the
      toxic tripeptide analogue, bialaphos. The introduction of the sum gene in
      multiple copies on a plasmid vector into the related strain Clostridium
      beijerinckii NCIMB 8052, resulted in inhibition of cell division, motility and
      autolysin activity. The sum gene appears to be a member of a new subgroup of
      activases with reducing activity, which may control a regulon affecting different
      stationary phase processes such as clostridial differentiation and sporulation in
      C. acetobutylicum P262. The metronidazole resistant phenotype of the sum mutant
      can be attributed to an increased capacity for DNA repair.

PMID- 16887618
TI  - Relationship between effect of ethanol on proton flux across plasma membrane and
      ethanol tolerance, in Pichia stipitis.
AB  - Pichia stipitis efficiently converts glucose or xylose into ethanol but is
      inhibited by ethanol concentrations exceeding 30 g/L. In Saccharomyces
      cerevisiae, ethanol has been shown to alter the movement of protons into and out
      of the cell. In P. stipitis the passive entry of protons into either glucose- or
      xylose-grown cells is unaffected at physiological ethanol concentrations. In
      contrast, active proton extrusion is affected differentially by ethanol,
      depending on the carbon source catabolized. In fact, in glucose-grown cells, the
      H(+)-extrusion rate is reduced by low ethanol concentrations, whereas, in xylose
      grown cells, the H(+)-extrusion rate is reduced only at non-physiological ethanol
      concentrations. Thus, the ethanol inhibitory effect on growth and ethanol
      production, in glucose-grown cells, is probably caused by a reduction in H(+)
      extrusion. Comparison of the rates of H(+)-flux with the related in vitro H(+)
      ATPase activity suggests a new mechanism for the regulation of the proton pumping
      plasma membrane ATPase (EC 3.6.1.3) of P. stipitis, by both glucose and ethanol.
      Glucose activates both the ATP hydrolysis and the proton-pumping activities of
      the H(+)-ATPase, whereas ethanol causes an uncoupling between the ATP hydrolysis
      and the proton-pumping activities. This uncoupling may well be the cause of
      ethanol induced growth inhibition of glucose grown P. stipitis cells.

PMID- 16887619
TI  - Virulence factors of oral treponemes.

PMID- 16887620
TI  - Adherence of Bilophila wadsworthia to cultured human embryonic intestinal cells.
AB  - Adherence of Bilophila wadsworthia to the cultured human embryonic intestinal
      cell line, Intestine 407 (Int 407), varied among the strains tested from strongly
      adherent (76-100% cells positive for one or more adherent bacteria) to non- or
      weakly adherent (0-25% positive cells). Although negative staining revealed that
      infrequent cells of an adherent strain, WAL 9077, the adherent type-strain, WAL
      7959, and a non-adherent strain, WAL 8448, expressed loosely associated fimbrial
      structures, a role for these structures in adhesion could not be confirmed with
      either scanning or thin-section electron micrography. Ruthenium red staining of
      thin-section preparations and subsequent electron microscopy failed to reveal an
      extensive extracellular polysaccharide layer. SDS-PAGE analysis of crude outer
      membrane fractions of WAL 9077 and WAL 8448 demonstrated clear differences in
      their major and minor outer membrane protein components. Thus, we postulate that
      the adherence of B. wadsworthia to Int 407 cells is mediated by an outer membrane
      or cell wall component.

PMID- 16887621
TI  - Comparison of E test and agar dilution methods for determining antibiotic
      susceptibilities of anaerobic bacteria and viridans streptococci isolated from
      blood.
AB  - The antimicrobial susceptibilities of 311 strains of anaerobic bacteria and 140
      strains of aerobic bacteria, isolated from blood after dental extraction, were
      determined by the E test and compared with the results obtained by the agar
      dilution method on PDM-ASM 2 agar. E test MICs agreed within +/-1 dilution step
      to the agar dilution MICs in 93%, 52%, 90%, 94% of the tested anaerobes for
      penicillin V, cefaclor, clindamycin and erythromycin, respectively. For aerobic
      bacteria the agreement was > or = 90% for the antibiotics tested. The in vitro
      activities of penicillin V, clindamycin and erythromycin were higher than the
      activity of cefaclor against the majority of bacteria tested.

PMID- 16887622
TI  - Features of Fibrobacter intestinalis DR7 mutant which is impaired with its
      ability to adhere to cellulose.
AB  - A spontaneous adhesion-defective mutant (DR7-M) of Fibrobacter intestinalis DR7
      was isolated which was capable of growing on glucose and cellobiose, but impaired
      in its capacity to degrade cellulose. Levels of enzyme activities were determined
      in solubilized fractions of DR7 and DR7-M. Total endoglucanases and xylanase
      activity values of parent DR7 fractions were 2.84 and 1.85 folds higher than
      those of the mutant, and were distributed mainly in the bacterial envelope
      fractions, with some activity also found in the extracellular fluid. In a
      separate assay, measurement of the enzymatic activity bound to cellulose showed
      that a portion of the endoglucanase activity bound to cellulose while most
      xylanase activity did not bind. Notwithstanding, the wild type DR7 cells had 26
      fold higher total activities of cellulose-degrading enzymes than the mutant, and
      96% of its activity was exclusively located in outer membrane and periplasm
      fractions. In the mutant, the lower cellulose degrading enzymes activity was
      located only in the extracellular fluid. Most of the cellulose degrading enzymes
      activity of DR7 had the capability to bind to cellulose. SDS-page electrophoresis
      of outer membrane and periplasm cell fractions showed that DR7 and DR7-M possess
      similar molecular weight (MW) profiles but different quantities of 16 cellulose
      binding-proteins (CBPs) in the MW range of 36 up to 225 kDa. Zymogram analysis
      with soluble substrates, either carboxymethylcellulose or soluble xylan,
      following SDS-page of DR7 and DR7-M fractions, suggested that CBPs of approximate
      MW 120, 110, 100, 90, 70 and 40 kDa have endoglucanase activity, and that CBPs of
      all fractions lack any xylanase activity.

PMID- 16887623
TI  - Molecular study and partial characterization of iron-only hydrogenase in
      Desulfovibrio fructosovorans.
AB  - An iron-only hydrogenase was partially purified and characterized from
      Desulfovibrio fructosovorans wild-type strain. The enzyme exhibits a molecular
      mass of 56 kDa and is composed of two distinct subunits HydA and HydB (46 and 13
      kDa, respectively). The N-terminal amino acid sequences of the two subunits of
      the enzyme were determined with the aim of designing degenerate oligonucleotides.
      Direct and inverse polymerase chain reaction techniques were used to clone the
      hydrogenase encoding genes. A 9-nucleotide region located 75 bp upstream from the
      translational start codon of the D. fructosovorans hydA gene was found to be
      highly conserved. The analysis of the deduced amino acid sequence of these genes
      showed the presence of a signal sequence located in the small subunit, exhibiting
      the consensus sequence which is likely to be involved in the specific export
      mechanism of hydrogenases. Two ferredoxin-like motives involved in the
      coordination of [4Fe-4S] clusters were identified in the N-terminal domain of the
      large subunit. The amino acid sequence of the [Fe] hydrogenase from D.
      fructosovorans was compared with the amino acid sequences from eight other
      hydrogenases (cytoplasmic and periplasmic). These enzymes share an overall 18%
      identity and 28% similarity. The identity reached 73% and 69% when the D.
      fructosovorans hydrogenase sequence was compared with the hydrogenase sequences
      from Desulfovibrio vulgaris Hildenborough and Desulfovibrio vulgaris oxamicus
      Monticello, respectively.

PMID- 16887624
TI  - Butyrivibrio spp. and other xylanolytic microorganisms from the rumen have
      cinnamoyl esterase activity.
AB  - High concentrations of hydroxycinnamic acids in the hemicellulosic fraction of
      dry season tropical grasses may influence the rate of microbial degradation of
      arabinoxylans by ruminant animals. The ability of 22 strains of Butyrivibrio
      fibrisolvens, other ruminal bacteria (Ruminococcus albus SY3, Ruminococcus
      flavefaciens RF1,Prevotella ruminicola AR20) and the ruminal phycomycete
      Neocallimastix patriciarum CX to digest the tropical grass Heteropogon
      contortus(spear grass) and hydrolyse esterified ferulic and p-coumaric acid was
      examined. Significant digestion (8-36%) of spear grass occurred with the B.
      fibrisolvens strains H17c, A38, LP92-1-1, 49,R. albus SY3 and N. patriciarum.
      Hydrolysis of ester-linked ferulic and p-coumaric acid occurred with all
      organisms except B. fibrisolvens strains GS113, OB156 and LP1028 and P.
      ruminicola AR20. The ratio of ferulic to p-coumaric acid hydrolysed by different
      strains of Butyrivibrio spp. varied markedly from 0.96 for AR 51 to 0.16 for A38.
      Butyrivibrios which were fibrolytic (H17c and A38) had higher extracellular
      cinnamoyl esterase activity than bacteria that did not digest spear grass fibre
      (LP 91-4-1 and AR 20) which had low activities or only produced cell associated
      enzyme. Cell associated and extracellular esterase activity were induced when
      Butyrivibrio spp. strains H17c, A38 and E14 and the Ruminococcus spp. were grown
      on birchwood xylan but induction did not occur to the same extent with N.
      patriciarum. This is the first reported observation of cinnamoyl esterase
      activity in the genus Ruminococcus. The fungus N. patriciarum had significantly
      higher digestibility of spear grass and solubilisation of phenolic acids than the
      bacteria. The study shows that high levels of extracellular cinnamoyl esterases
      are characteristic of a selection of fibre-degrading ruminal bacteria and fungi
      which probably indicates that these enzymes are common amongst xylanolytic
      ruminal microorganisms.

PMID- 16887625
TI  - Phenotypic characterization of enterotoxigenic Clostridium perfringens isolates
      from non-foodborne human gastrointestinal diseases.
AB  - Clostridium perfringens enterotoxin (CPE) has been implicated as an important
      virulence factor inC. perfringens type A food poisoning and several non-foodborne
      human gastrointestinal (GI) illnesses, including antibiotic-associated diarrhea
      (AAD) and sporadic diarrhea (SPOR). Recent studies have revealed genotypic
      differences between cpe-positive isolates originating from different disease
      sources, with most, or all, food poisoning isolates carrying a chomosomal cpe and
      most, or all, non-foodborne human GI disease isolates carrying an episomal cpe.
      To evaluate whether these genotypic differences cause phenotypic effects that
      could influence the pathogenesis of CPE-associated non-foodborne human GI
      illnesses, a collection of SPOR and AAD isolates has been phenotypically
      characterized in the current study. All cpe-positive non-foodborne disease
      isolates examined were found to express CPE in a sporulation-associated manner.
      The CPE made by these AAD and SPOR isolates was shown to have the same deduced
      amino acid sequence and toxicity as the classical CPE made by food poisoning
      isolates. All of the surveyed non-foodborne human GI disease isolates were found
      to classify as type AC. perfringens, since they produce alpha toxin, but not
      beta, iota, or epsilon toxins. Finally, no consistent clonal relationships were
      detected between the surveyed non-foodborne human GI disease isolates. Since, by
      the criteria examined, all non-foodborne human GI disease isolates examined in
      this study appear to be phenotypically similar to food poisoning isolates, the
      current results confirm that the examined AAD and SPOR isolates have
      enteropathogenic potential. However, given the phenotypic similarities between
      food poisoning, AAD, and SPOR isolates that have been demonstrated in this study,
      it remains unclear why the symptomology of non-foodborne human GI diseases is
      typically more severe and longer-lasting than that of C. perfringens type A food
      poisoning.

PMID- 16887626
TI  - Microbial mineralization of VC and DCE under different terminal electron
      accepting conditions.
AB  - Production of 14CO2 from [1,2-14C] dichloroethene (DCE) or [1,2-14C] vinyl
      chloride (VC) was quantified in aquifer and stream-bed sediment microcosms to
      evaluate the potential for microbial mineralization as a pathway for DCE and VC
      biodegradation under aerobic, Fe(III)-reducing, SO4-reducing, and methanogenic
      conditions. Mineralization of [1,2-14C] DCE and [1,2-14C] VC to 14CO2 decreased
      under increasingly reducing conditions, but significant mineralization was
      observed for both sediments even under anaerobic conditions. VC mineralization
      decreased in the order of aerobic > Fe(III)-reducing > SO4-reducing >
      methanogenic conditions. For both sediments, VC mineralization was greater than
      DCE mineralization under all electron-accepting conditions examined. For both
      sediments, DCE mineralization was at least two times greater under aerobic
      conditions than under anaerobic conditions. Although significant microbial
      mineralization of DCE was observed under anaerobic conditions, recovery of 14CO2
      did not differ substantially between anaerobic treatments.

PMID- 16887627
TI  - Isolation from the rumen of a new acetogenic bacterium phylogenetically closely
      related to Clostridium difficile.
AB  - Five strains of filamentous acetogenic bacterium were isolated from high
      dilutions of ruminal content of newborn lambs. These Gram-positive spore-forming
      bacteria grew either chemolithotrophically with H2+ CO2 or chemo
      organotrophically with glucose, cellobiose, fructose, maltose, mannose and
      syringic acid. The DNA base composition of the five strains were between 29.1 and
      31.3 mol% G + C. Their temperature and pH optimum for growth were 35-40 degrees C
      and 6.5-7.0, respectively. The full 16S rRNA gene sequence analysis of the
      reference strain indicated that it was most closely related to Clostridium
      difficile. The sequence similarity value between the 16S rRNA gene of the
      reference strain and this pathogenic strain was 99.7%.

PMID- 16887628
TI  - Degradation of 2-nitrodiphenylamine, a component of Otto Fuel II, by Clostridium
      spp.
AB  - Otto Fuel II, a propellant in torpedoes, is composed of 76% 1,2 propanediol
      dinitrate (PGDN), 22.5% di-n-butyl sebacate, and 1.5% 2-nitrodiphenylamine
      (NDPA), and is largely recalcitrant to aerobic microbial degradation. Anaerobic
      microbial degradation of Otto Fuel II was tested by inoculating anaerobic
      enrichment media, containing either 2% (vol:vol) complete Otto Fuel II or 2% of a
      0.02% solution of Otto Fuel II in methanol, with soil and water from sites
      contaminated with munitions or with landfill leachate. Anaerobic bacterial growth
      was completely inhibited by 2% Otto Fuel II. Two mixed bacterial enrichments
      developed in anaerobic media containing 2% (v/v) of a 0.02% solution of Otto Fuel
      II in methanol. After incubation, PGDN could not be detected in either
      enrichment, but was also not detectable in sterile controls, suggesting abiotic
      degradation of low concentrations of PGDN in reduced anaerobic medium. NDPA did
      not degrade in either enrichment. Similarly, complete Otto Fuel was recalcitrant
      to degradation by highly reducing methanogenic biomass collected from an upflow
      anaerobic sludge blanket bioreactor (UASB). A comparison of the degradative
      ability of autoclaved and viable biomass showed that low concentrations of PGDN
      autodegraded, however unlike the autoclaved anaerobic biomass, the viable
      anaerobic biomass degraded the NDPA component of Otto Fuel II. Two strains of
      anaerobic clostridia, strains SP3 and SPF, that caused the disappearance of NDPA
      at its limit of solubility in culture media, were isolated from the UASB
      bioreactor biomass. SP3 and SPF were shown, by comparison of 16S rDNA sequences,
      to be most closely related to Clostridium butyricum and Clostridium cochlearium
      respectively. Although NDPA was lost from cultures of both strains, metabolic end
      products were not identified. Neither strain could degrade NDPA unless supplied
      with an alternative energy source. In the culture system used, NDPA stimulated
      the growth of SP3 but it had no appreciable effect on the growth of SPF. Both SP3
      and SPF degraded low concentrations of trinitrotoluene (TNT), without the
      production of detectable concentrations of aromatic amines. A possible method for
      the remediation of small spills of Otto Fuel II is suggested.

PMID- 16887629
TI  - Effects of host iron transport compounds on growth kinetics and outer-membrane
      protein expression of Bilophila wadsworthia.
AB  - Since the environmental iron concentration has emerged as an important attribute
      in the expression of bacterial virulence, the purpose of this study was to
      determine the effects of transferrin, lactoferrin, heme compounds, and inorganic
      iron sources (ferric and ferrous sulfate) on the growth of Bilophila wadsworthia
      and to study its outer membrane composition when grown under these different
      simulated in vivo conditions. Lactoferrin, transferrin, hemin and hemoglobin
      supported full growth of the bacteria in media lacking other iron sources.
      Bilophila wadsworthia was also capable of growing in the presence of ferrous and
      ferric sulfate. Profiles obtained by SDS-PAGE showed two iron-regulated outer
      membrane proteins (IROMPs) of 190 kDa and 88 kDa. The 190 kDa was susceptible to
      proteinase K cleavage in whole cells, indicating its exposure at the cell
      surface. These two major IROMPs were expressed in iron-restricted media
      supplemented with iron-bound organic sources and repressed by the addition of
      inorganic iron sources.

PMID- 16887630
TI  - The behaviour of Fusobacterium nucleatum chemostat-grown in glucose- and amino
      acid-based chemically defined media.
AB  - Fusobacterium nucleatum is a Gram-negative anaerobe, found in a number of
      different areas of human and animal bodies as part of the resident microbiota.
      However, it also appears to be involved in polymicrobial infections in such
      sites. It occurs in the oral cavity where it is a prominent member of various
      bacterial consortia associated with periodontal diseases. Like most fusobacteria,
      it derives energy via the fermentation of amino acids which it can obtain through
      the dissimilation of small peptides. However, the role of simple carbohydrates,
      such as glucose, in its growth and metabolism are not well understood.
      Accordingly, the aim of the present study was to study the behaviour ofF.
      nucleatum grown anaerobically in continuous culture in two different chemically
      defined media (CDM); one containing only amino acids as the energy source, the
      other containing glucose as the predominant energy provider. At various dilution
      rates the culture were assayed for dry weight, intracellular polyglucose (IP)
      content, residual amino acids and glucose and acidic metabolic end-products. In
      the carbohydrate-free CDM the acidic end-products were a constant acetate :
      butyrate : formate of 1.5 : 1 : 0.4. The values of Y(max)amino acids, maximum
      yield of bacteria per mol of amino acids consumed, for two strains were estimated
      to be 15.2 and 18.6 g dry wt/mol, respectively. Them(amino acids), maintenance
      energy requirement for growth on amino acids, for the two strains was 0.81 and
      0.94 mmol/g dry wt/h, respectively. Growth of one strain in the glucose-based CDM
      gave an estimated Y(max)glucose of 67.2 and an m(glucose) of 0.38; the acidic end
      products were a fairly constant acetate : butyrate : formate : lactate of 0.7 : 1
      : 0.3 : 2.5. Only at low growth rates, and then only in small amount, was IP
      produced in this medium. Overall, it was concluded that the occurrence of F.
      nucleatum in widely-differing oral niches may be explained, at least in part, by
      its metabolic versatility.

PMID- 16887631
TI  - Isolation and characterisation of a novel sulphate-reducing bacterium of the
      Desulfovibrio genus.
AB  - A novel sulphate-reducing bacterium (Ind 1) was isolated from a biofilm removed
      from a severely corroded carbon steel structure in a marine environment. Light
      microscopy observations revealed that cells were Gram-negative, rod shaped and
      very motile. Partial 16S rRNA gene sequencing and analysis of the fatty acid
      profile demonstrated a strong similarity between the new species and members from
      the Desulfovibrio genus. This was confirmed by the results obtained following
      purification and characterisation of the key proteins involved in the sulphate
      reduction pathway. Several metal-containing proteins, such as two periplasmic
      proteins: hydrogenase and cytochrome c3, and two cytoplasmic proteins: ferredoxin
      and sulphite reductase, were isolated and purified. The latter proved to be of
      the desulfoviridin type which is typical of the Desulfovibrio genus. The study of
      the remaining proteins revealed a high degree of similarity with the homologous
      proteins isolated from Desulfovibrio gigas. However, the position of the strain
      within the phylogenetic tree clearly indicates that the bacterium is closely
      related to Desulfovibrio gabonensis, and these three strains form a separate
      cluster in the delta subdivision of the Proteobacteria. On the basis of the
      results obtained, it is suggested that Ind 1 belongs to a new species of the
      genus Desulfovibrio, and the name Desulfovibrio indonensis is proposed.

PMID- 16887633
TI  - Induction of release of tumor necrosis factor and IL-6 from human mononuclear
      cells by Bacteroides strains.
AB  - The role of anaerobic Gram-negative bacteria in inducing cytokines during mixed
      infections involving aerobic and anaerobic bacteria is relatively poorly defined.
      The purpose of this study was to establish whether or not intact Bacteroides
      fragilis and related species, isolated from severe infections and from the faeces
      of healthy persons are capable of releasing tumor necrosis factor (TNF) and IL-6
      from human mononuclear cells and whole blood. The purified lipopolysaccharides of
      Bacteroides fragilis strain (No. 7), extracted by the aqueous phenol method from
      BHI cultures and from BHI culture supplemented with 5% horse serum, were also
      tested. TNF release was detected by the WEHI 164-dependent bioassay and IL-6
      production by the B-9 cell-dependent bioassay. Heat-inactivated Bacteroides
      strains belonging to different species were able to induce TNF (1x10(1)-5x10(2)
      U/mL) and IL-6 (1x10(1)-5x10(5) pg/mL) release from human mononuclear cells. When
      whole blood was used, the production of TNF and IL-6 was more pronounced (very
      probably because of the presence of certain serum factors). The culturing
      conditions (the presence of 5% horse serum in the BHI broth) influenced the
      inducing activity of almost all strains tested. The isolated lipopolysaccharide
      of Bacteroides fragilis strain No. 7 proved to have a rough profile on PAGE.
      There were no differences in TNF and IL-6 induction when the lipopolysaccharides
      of the strain was cultured in BHI or in BHI supplemented with 5% horse serum.
      Bacteroides strains often outnumber Enterobacteriaceae in the faeces and in mixed
      infections, and their role in inducing and/or modulating the host response in
      septic shock should not be overlooked.

PMID- 16887634
TI  - apaH polymorphism in Clinical Actinobacillus actinomycetemcomitans isolates.
AB  - In the present study the apaH polymorphism in clinical A. actinomycetemcomitans
      isolates were investigated in relation to their serotype and periodontal status
      of the donor subjects. The material included 122A. actinomycetemcomitans isolates
      representing serotypes a-e from 103 periodontally healthy and diseased subjects.
      The apaH polymorphism was investigated by both restriction analysis of the
      specific PCR amplification product and also by sequencing of PCR amplification
      products from selected clinical isolates. An apaH specific PCR amplification
      product was obtained from all isolates but the restriction patterns of the
      amplification products varied. Serotype c and genogroup 2 within serotype e
      formed genetically distinct groups, whereas isolates of serotype a, b, d and
      genogroup 1 within serotype e could not be separated from each other based on the
      apaH restriction analysis. No relation between the restriction pattern of apaH
      and the periodontal status of the individuals was detected. These results
      indicate that serotype c isolates form a uniformly distinct group within A.
      actinomycetemcomitans and that a subpopulation of serotype e isolates clearly
      diverge from all other A. actinomycetemcomitans isolates.

PMID- 16887635
TI  - Estimation of the growth rate of mixed ruminal bacteria from short-term DNA
      radiolabeling.
AB  - A method based on 32P-labeling of DNA in short-term incubations was developed for
      estimating the growth rate of mixed rumen bacteria. A freeze/thaw procedure was
      optimized to quantitatively disrupt mixed rumen bacteria and extract bacterial
      DNA. The preliminary enzymatic lysis step, with lysozyme rather than proteinase
      K, sodium lauroyl sarcosine, and, to a lesser extent, sodium dodecyl sulfate
      (SDS) strongly improved cell disruption and DNA recovery rates. Sodium
      deoxycholate, CHAPS or Triton X-100 had no significant effect. Increasing the
      number of cycles or lowering the freezing temperature from -20 degrees C to -50
      degrees C had no effect on DNA extraction efficiency while setting the thawing
      temperature at +60 degrees C rather than +37 degrees C slightly increased DNA
      yield but also increased its contamination with RNA. The method finally selected
      led to the lysis of at least 93% of cells and to the extraction of 85% of
      bacterial DNA. The kinetics of in vitro 32P incorporation into rumen bacteria DNA
      was then determined in batch incubations of strained rumen contents with no
      additional substrate. The curvilinear effects of the amount of 32P and the
      incubation time (5-15 min) on the DNA radioactivity were investigated by applying
      a Doehlert experimental design and fitting a second order polynomial model to
      data. The DNA radioactivity was linearly related to time (p<0.02) with other
      coefficients in the model being equal to zero (p>0.20). The incorporation of 32P
      into bacterial DNA was initiated approximately 70 s after the start of
      incubation. Taking into account the accuracy of scintillation counting, 10-15 min
      incubations, with 15 microCi 32P and 10 mL rumen contents per tube, appeared
      satisfactory for future studies.

PMID- 16887636
TI  - Phylogenetic analysis of rumen bacteria by comparative sequence analysis of
      cloned 16S rRNA genes.
AB  - Comparative DNA sequence analysis of 16S rRNA genes (rDNA) was undertaken to
      further our understanding of the make-up of bacterial communities in the rumen
      fluid of dairy cattle. Total DNA was extracted from the rumen fluid of 10 cattle
      fed haylage/corn silage/concentrate rations at two different times. Rumen samples
      were collected on two separate occasions from five cows each. In experiment 1, 31
      cloned rDNA sequences were analysed. In experiment 2, DNA extractions were
      amplified using either 12 or 30 cycles of PCR in order to examine biases
      introduced during the reactions. A set of 53 sequences were analysed in
      experiment 2 from DNA amplified using 12 cycles and 49 sequences from PCR using
      30 cycles. Sequences from the 5' end of 16S rRNA gene were compared with existing
      sequences in the Ribosomal Database Project. Clones from experiment 1 produced a
      data set in which 55% of the sequences were similar to low G+C Gram-positive
      bacteria related to the genus Clostridia, the majority of which were closely
      related to bacteria in Cluster XIV. Approximately 30% of the cloned sequences
      were related to bacteria in the Prevotella-Bacteroides group. Clones from
      experiment 2 produced a data set in which the majority of sequences were related
      to the Prevotella-Bacteroides group, regardless of the number of cycles of PCR.
      The remaining sequences clustered with members of the genus Clostridia. The
      majority of rDNA sequences analysed in this study represent novel rumen bacteria
      which have not yet been isolated.

PMID- 16887637
TI  - Identification and Phylogenetic analysis of thermophilic sulfate-reducing
      bacteria in oil field samples by 16S rDNA gene cloning and sequencing.
AB  - Thermophilic sulfate-reducing bacteria (SRB) have been recognized as an important
      source of hydrogen sulfide (H2S) in hydrocarbon reservoirs and in production
      systems. Four thermophilic SRB enrichment cultures from three different oil field
      samples (sandstone core, drilling mud, and production water) were investigated
      using 16S rDNA sequence comparative analysis. In total, 15 different clones were
      identified. We found spore-forming, low G+C content, thermophilic, sulfate
      reducing Desulfotomaculum-related sequences present in all oil field samples, and
      additionally a clone originating from sandstone core which was assigned to the
      mesophilic Desulfomicrobium group. Furthermore, three clones related to Gram
      positive, non-sulfate-reducing Thermoanaerobacter species and four clones close
      to Clostridium thermocopriae were found in enrichment cultures from sandstone
      core and from production water, respectively. In addition, the deeply rooted
      lineage of two of the clones suggested previously undescribed, Gram-positive, low
      G+C content, thermophilic, obligately anaerobic bacteria present in production
      water. Such thermophilic, non-sulfate-reducing microorganisms may play an
      important ecological role alongside SRB in oil field environments.

PMID- 16887639
TI  - Classification of Clostridium butyricum based on sodium dodecyl sulfate
      polyacrylamide gel electrophoresis and pulsed-field gel electrophoresis.
AB  - Eleven strains of Clostridium butyricum collected from different sources were
      analysed by both sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS
      PAGE) and pulsed-field gel electrophoresis (PFGE). The strains could be
      classified into four groups based on their banding profiles of the proteins
      extracted from the cells on SDS-PAGE. Group I consisted of seven strains, and
      these strains were further divided into five subgroups by PFGE. The strains
      belonging to groups II, III, and IV on SDS-PAGE were also classified into the
      same II to IV groups by PFGE. These data indicate that grouping of the strains of
      C. butyricum can be performed by employing both SDS-PAGE and PFGE.

PMID- 16887640
TI  - Colonisation of Clostridium in the body is restricted to hypoxic and necrotic
      areas of tumours.
AB  - The use of gene therapy is one of the most recent molecular strategies for the
      treatment of cancer. It is essential, however, to have an efficient transfer
      system by which the desired gene can be delivered to the correct environment. The
      experiments described in this report investigate apathogenic Clostridium as a
      possible vector to transfer a specific gene product into the extracellular
      microenvironment of the tumour which is hypoxic/necrotic in parts, using WAG/Rij
      rats with transplantable rhabdomyosarcomas as a model. Our data show that
      Clostridium, after systemic administration of at least 10(7) spores, specifically
      colonises the hypoxic/necrotic areas of our tumour model, the most efficient
      species being C. acetobutylicum (NI-4082) and C. oncolyticum. Although spores
      were also detected in normal tissues for up to 4 weeks, they did not germinate in
      these tissues. We conclude that it seems likely that these bacteria can be used
      as a selective transfer system into the extracellular environment of tumours
      which have hypoxic regions. This strategy would be more tumour-specific than
      various other strategies that are currently being investigated in anti-cancer
      gene therapy.

PMID- 16887641
TI  - Identification of Bacteroides fragilisby a modified immuno polymerase chain
      reaction (mIPCR), using a specific monoclonal antibody.
AB  - Bacteroides fragilis is the anaerobic species most commonly isolated from human
      clinical specimens, and is resistant to many antimicrobial agents. A monoclonal
      antibody, mAb4H8 (IgG3), reacting with a specific epitope in the
      lipopolysaccharide (LPS) isolated from most of the B. fragilis strains, was
      produced and employed with modified Immuno Polymerase Chain Reaction (mIPCR) for
      identification of B. fragilis with a detection limit of 10(4) cfu/mL bacterial
      suspension. A number of bacterial strains were examined, including B. fragilis,
      Bacteroides spp. other than B. fragilis and other genera. All the B. fragilis
      strains with the immunodominant (beta1,6-linked D-galactosyl chain) epitope were
      positive. None of the other strains showed the positive reaction. The results
      indicate that mIPCR assay with mAb4H8 has a high specificity and high
      sensitivity.

PMID- 16887643
TI  - Ralph S. Wolfe (1921-). Pioneer of biochemistry of methanogenesis.

PMID- 16887642
TI  - Effect of specific inhibitors on the anaerobic reductive dechlorination of 2,4,6
      trichlorophenol by a stable methanogenic consortium.
AB  - The transformation of 2,4,6-trichlorophenol (TCP) into 4-chlorophenol (4CP) was
      studied using a stable methanogenic enrichment culture derived from an anaerobic
      fixed bed reactor. Using acetate as a growth substrate, different inhibitors of
      methanogenesis exhibited distinct effects on TCP dechlorination. Whereas
      reductive dechlorination activity was not affected by 2% ethylene in the gas
      phase, 25 mM bromoethanesulfonic acid (BESA) had a direct inhibitory effect on
      this process. The choice of BESA as a specific inhibitor for identifying the
      subpopulations involved in reductive dechlorination of chloroaromatics is thus
      questionable. Inhibitors of sulfate reduction such as molybdate (20 mM) and
      selenate (20 mM) had a direct inhibitory effect on reductive dechlorination
      independently of the presence of sulfate in the medium supplemented with acetate
      as growth substrate. Consequently much more care must also be taken with these
      inhibitors to prove that reductive chlorination is coupled to sulfate reduction.

PMID- 16887644
TI  - Preterm labor and bacterial intra-amniotic infection: arachidonic acid liberation
      by phospholipase A2 of Prevotella bivia.
AB  - There is a strong association between preterm labor and infection, presumably
      through an increase in prostaglandin formation. The studies presented in this
      report were undertaken to evaluate whether Prevotella bivia, a common anaerobic
      isolate of intrauterine infection, stimulates arachidonic acid metabolism, as a
      rate-limiting step for prostaglandin synthesis in the human uterine endometrium.
      When human uterine endometrial cells prelabeled with [3H]arachidonic acid to an
      isotopically steady state were exposed to an extract of P. bivia, arachidonic
      acid liberation was stimulated, accompanied by lysophospholipid formation.
      Similar stimulatory effect on phospholipid degradation was also observed in the
      experiment with the bacterial conditioned media which was spent as culture media.
      These results suggests that P. bivia stimulates endometrial phospholipid
      metabolism, related with activity of phospholipase A2, which might induce the
      onset of labor associated with intra-amniotic infection.

PMID- 16887645
TI  - Ribotyping of Fusobacterium necrophorum strains isolated from bovine and ovine
      hepatic abscesses.
AB  - A microbiological study was made of 100 strains of Fusobacterium necrophorum
      isolated from hepatic abscesses in bovine and ovine herds. Differences between
      the biological activity and ribotypes within the two F. necrophorum subspecies
      were studied. Conventional methods identified 89 isolates as F. necrophorum
      subsp. necrophorum and 11 as F. necrophorum subsp. funduliforme. For ribotyping,
      50 strains (35 F.n. subsp. necrophorum, 11 F.n. subsp. funduliforme and 4
      reference strains) were digested with restriction endonucleases (HindIII, EcoRI
      and BamHI) and examined after hybridization with digoxigenin-labelled cDNA probe
      transcribed from a 16 and 23S rRNAs from Escherichia coli. The most
      discriminating restriction endonuclease enzymes for ribotyping were EcoRI and
      BamHI. The presence or absence of two distinct band of 5 kb (EcoRI) and 10.5 kb
      (BamHI) differentiated the two subspecies. This technique also revealed genetic
      differences between isolates which could be used in the epidemiological study of
      clinical processes caused by F. necrophorum.

PMID- 16887646
TI  - Start-up of an anaerobic hybrid (UASB/filter) reactor treating wastewater from a
      coffee processing plant.
AB  - The ability of an anaerobic hybrid reactor, treating coffee wastewater, to
      achieve a quick start-up was tested at pilot scale. The unacclimatized seed
      sludge used showed a low specific methanogenic activity of 26.47 g CH4 as
      chemical oxygen demand (COD)/kg volatile suspended solids (VSS) x day. This
      strongly limited the reactor performance. After a few days of operation, a COD
      removal of 77.2% was obtained at an organic loading rate (OLR) of 1.89 kg COD/m3
      x day and a hydraulic retention time (HRT) of 22 h. However, suddenly increasing
      OLR above 2.4 kg COD/m3 x day resulted in a deterioration in treatment
      efficiency. The reactor recovered from shock loads after shutdowns of 1 week. The
      hybrid design of the anaerobic reactor prevented the biomass from washing-out but
      gas clogging in the packing material was also observed. Wide variations in
      wastewater strength and flow rates prevented stable reactor operation in the
      short period of the study.

PMID- 16887647
TI  - FgoI, a Type II restriction endonuclease from the thermoanaerobe Fervidobacterium
      gondwanense AB39(T).
AB  - Restriction endonuclease activity was detected in 11 out of 13 Fervidobacterium
      isolates, including F. islandicum H21(T), F. gondwanense AB39(T), and nine other
      Fervidobacterium-like strains isolated from the Great Artesian Basin of
      Australia. The restriction endonuclease from F. gondwanense AB39(T) was partially
      purified and designated FgoI. FgoI recognized a 4 nucleotide sequence 5'-CTAG-3'
      and cleaved between nucleotides C and T to produce a 2 base 5' overhang (5'-C/TAG
      3'). As predicted from the enzyme recognition and cleavage specificity, FgoI was
      found to cleave delta DNA 13 times, phiX174 three times, pBR322 five times, pUC18
      four times, and pSK six times. FgoI exhibited a broad temperature optimum range
      (between 60 to 70 degrees C) and was active at pH 6.5 to 8.5, but not at pH 9.0.
      Manganese could replace magnesium as a cofactor for activity, but not cobalt
      chloride, calcium chloride, cupric chloride, or zinc chloride. The restriction
      endonuclease was completely inactivated by phenol/chloroform extraction and was
      heat inactivated at 80 degrees C for 60 min or at 100 degrees C for 15 min. FgoI
      has been identified as a heat stable isoschizomer of the Type II restriction
      endonucleases, MaeI and BfaI.

PMID- 16887648
TI  - Isolation and characterization of non-pigmented rough colony of Porphyromonas
      gingivalis from periodontitis.
AB  - During isolation of Porphyromonas gingivalis from periodontal pockets of
      patients, the appearance of an unusual rough colony form, designated NUM 114, was
      observed. The NUM 114 strain grew in aggregated cell form in a liquid culture and
      formed a light-beige rough colony on blood agar medium. The identifications and
      DNA studies confirmed that the NUM 114 strain was P. gingivalis. The enzymatic
      activities and fatty acid end products were in lower levels than found in P.
      gingivalis 381, a representative strain. The NUM 114 strain had enhanced
      hydrophobicity, hemagglutination of human erythrocytes and adherence to human
      buccal epithelial cells. The NUM 114 cells were phagocytized at a two-fold higher
      rate compared with the 381 strain. NUM 114 cells were also more susceptible to
      killing by phagocytosis than the 381 cells. The carbohydrates of the outer
      membrane and crude lipopolysaccharide preparation from the NUM 114 strain were in
      larger amounts than those of 381 strain. LPS from NUM 114 were observed to be
      smooth-type.

PMID- 16887649
TI  - Aminobacterium colombiensegen. nov. sp. nov., an amino acid-degrading anaerobe
      isolated from anaerobic sludge.
AB  - A new gram-negative, non-sporulating, mesophilic, amino acid fermenting
      bacterium, designated strain ALA-1(T) (T = type strain), was isolated from an
      anaerobic lagoon of a dairy wastewater treatment plant. The strain is curved (3-4
      microm x 0.2-0.3 microm) and occurs singly or in pairs. Optimum growth occurs at
      37 degrees C and pH 7.3. The G+C content of the DNA is 46 mol %. The strain
      requires yeast extract for growth, grows poorly on casamino acids, peptones,
      cysteine, and alpha-ketoglutarate, but readily grows on serine, threonine,
      glycine and pyruvate. When cocultured with the hydrogenotrophic methanogen
      Methanobacterium formicicum, strain ALA-1(T) oxidized alanine, glutamate,
      leucine, isoleucine, valine, aspartate, and methionine. Phylogenetic analysis
      revealed that it forms a distinct and independent line of descent in the vicinity
      of Dethiosulfovibrio peptidovorans, Dictyoglomus thermophilum, and Anaerobaculum
      thermoterrenum which are members of the low G+C containing gram-positive
      bacteria. The phylogenetic results concur with the phenotypic and genomic data
      which reveal that it is a novel strain. Based on these findings, we designate
      strain ALA-1(T) as Aminobacterium colombiense (DSM 12261) gen. nov., sp. nov.

PMID- 16887650
TI  - Survival of a Salmonella typhimurium poultry isolate in the presence of propionic
      acid under aerobic and anaerobic conditions.
AB  - Propionic acid is commonly found as a fermentation product in the
      gastrointestinal tracts of food animals and has also been used to limit the
      microbial contaminants in animal feeds. Because propionic acid is known to have
      antibacterial activity, the propionic acid encountered by foodborne pathogens
      during their life cycles may play an important role in inhibiting the survival of
      the pathogens. The survival patterns of Salmonella typhimurium poultry isolate
      were determined both in aerobic and anaerobic tryptic soy broth (TSB; pH 5.0 or
      7.0) containing various concentrations of propionic acid (0-200 mM). The levels
      of recovered cells were consistently greater at pH 7.0 compared to those at pH
      5.0. For the first 4 days, the levels were significantly decreased by incubation
      under anaerobic conditions as compared to aerobic condition at pH 7.0 (P<0.05).
      However, there were fluctuations of cell populations with different patterns
      depending on both concentrations and growth conditions. To characterize the
      nature of the capability which allowed the cell multiplication following
      decreases in cell population during incubation at pH 7.0, the cells isolated from
      the outgrowth cultures were tested for survival in aerobic or anaerobic TSB (pH
      5.0 or pH 7.0) containing propionic acid (50 mM). The outgrowth isolates did not
      show significant differences in the level of recovered cells in the presence of
      propionic acid when compared to the wild type strain (P>0.05), suggesting that
      the cells in the outgrowth cultures did not harbour mutation(s) conferring
      increased resistance to propionic acid. In addition, the level of recovered cells
      of isogenic rpoS mutant strain of S. typhimurium was not significantly different
      from that of the wild type strain in the same assay conditions (P<0.05). The
      results of this study show that the bactericidal activity of propionic acid on S.
      typhimurium can be affected by environmental conditions such as acidic pH levels
      and anaerobiosis in food materials and gastrointestinal tracts. However, S.
      typhimurium is also able to multiply in the presence of sublethal concentrations
      of propionic acid at neutral pH during prolonged incubation under both aerobic
      and anaerobic conditions.

PMID- 16887651
TI  - In vitro prebiotic effects of Acacia gums onto the human intestinal microbiota
      depends on both botanical origin and environmental pH.
AB  - Acacia gums are commonly used food additives. It is currently unclear how
      extensively these non-digestible polysaccharides are fermented in the human large
      intestine. However, they have been shown to support bifidobacterial growth in
      vitro and may represent useful candidate prebiotics. In these investigations, in
      vitro 24-h batch incubations and chemostat continuous-cultures of human faecal
      bacteria were conducted using two acacia gums (Fibregum standard and Fibregum
      AS). Our aim was to study the effects of these gums on bacterial ecology and
      fermentation in the large bowel. Fructooligosaccharides (Actilight-950P) were
      also investigated as a reference. Both Acacia gums were extensively fermented by
      intestinal flora although there were marked differences in fermentation product
      formation and ecological effects, probably due to their differing botanical
      origins and/or biochemical characteristics. In particular, fermentation of
      Fibregum AS led to significantly higher proportions of propionate both in batch
      and chemostat experiments. Both gums decreased Clostridium sp. levels but only
      Fibregum-standard induced higher Lactobacillus sp. counts compared to control.
      These bacterial modifications were highly dependent of the operating pH of the
      fermentation system with acidic conditions promoting both the prebiotic and the
      butyrogenic effects of fructooligosaccharides. In these studies, we have
      demonstrated that, similarly to fructooligosaccharides, Acacia gums can exert
      putatively beneficial effects on host health through both the improvement of the
      composition of the large intestine microflora and SCFA formation.

PMID- 16887652
TI  - 16S rDNA sequence diversity of a culture-accessible part of an anaerobic digestor
      bacterial community.
AB  - A bacterial culture-based inventory with 16S rDNA identification of the isolates
      was carried out on an anaerobic digestor microbial ecosystem to compare to the
      16S rDNA sequences directly retrieved from the ecosystem by a molecular inventory
      previously made in our laboratory. Twenty OTUs (Operational Taxonomic Units)
      belonging to five of the major bacterial groups were identified from 338 isolated
      colonies. The sequences of 13 of the 20 OTUs were not closely related to any
      hitherto published sequences (less than 96% sequence identity). Six OTUs out of
      20 were found to have sequences similar to sequences of the molecular inventory.
      Despite the biases expected to be associated with the molecular and culture-based
      methods, the distribution of the isolated OTUs into the different bacterial phyla
      was similar to that of the molecular OTUs.

PMID- 16887653
TI  - Carbohydrate oxidation coupled to Fe(III) reduction, a novel form of anaerobic
      metabolism.
AB  - An isolate, designated GC-29, that could incompletely oxidize glucose to acetate
      and carbon dioxide with Fe(III) serving as the electron acceptor was recovered
      from freshwater sediments of the Potomac River, Maryland. This metabolism yielded
      energy to support cell growth. Strain GC-29 is a facultatively anaerobic, gram
      negative motile rod which, in addition to glucose, also used sucrose, lactate,
      pyruvate, yeast extract, casamino acids or H2 as alternative electron donors for
      Fe(III) reduction. Stain GC-29 could reduce NO3(-), Mn(IV), U(VI), fumarate,
      malate, S2O3(2-), and colloidal S0 as well as the humics analog, 2,6
      anthraquinone disulfonate. Analysis of the almost complete 16S rRNA sequence
      indicated that strain GC-29 belongs in the Shewanella genus in the epsilon
      subdivision of the Proteobacteria. The name Shewanella saccharophilia is
      proposed. Shewanella saccharophilia differs from previously described
      fermentative microorganisms that metabolize glucose with the reduction of Fe(III)
      because it transfers significantly more electron equivalents to Fe(III); acetate
      and carbon dioxide are the only products of glucose metabolism; energy is
      conserved from Fe(III) reduction; and glucose is not metabolized in the absence
      of Fe(III). The metabolism of organisms like S. saccharophilia may account for
      the fact that glucose is metabolized primarily to acetate and carbon dioxide in a
      variety of sediments in which Fe(III) reduction is the terminal electron
      accepting process.

PMID- 16887654
TI  - Eubacterium aggreganssp. nov., a new homoacetogenic bacterium from olive mill
      wastewater treatment digestor.
AB  - A strictly anaerobic, homoacetogenic, gram-positive, non spore-forming bacterium,
      designated strain SR12(T) (T = type strain), was isolated from an anaerobic
      methanogenic digestor fed with olive mill wastewater. Yeast extract was required
      for growth but could also be used as sole carbon and energy source. Strain
      SR12(T) utilized a few carbohydrates (glucose, fructose and sucrose), organic
      compounds (lactate, crotonate, formate and betaine), alcohols (methanol), the
      methoxyl group of some methoxylated aromatic compounds, and H2 + CO2. The end
      products of carbohydrate fermentation were acetate, formate, butyrate, H2 and
      CO2. End-products from lactate and methoxylated aromatic compounds were acetate
      and butyrate. Strain SR12(T) was non-motile, formed aggregates, had a G+C content
      of 55 mol % and grew optimally at 35 degrees C and pH 7.2 on a medium containing
      glucose. Phylogenetically, strain SR12(T) was related to Eubacterium barkeri, E.
      callanderi, and E. limosum with E. barkeri as the closest relative (similarity of
      98%) with which it bears little phenotypic similarity or DNA homology (60%). On
      the basis of its phenotypic, genotypic, and phylogenetic characteristics, we
      propose to designate strain SR12(T) as Eubacterium aggregans sp. nov. The type
      strain is SR12(T) (= DSM 12183).

PMID- 16887655
TI  - Peptostreptococcus ivorii-associated skin abscess in a HIV-infected patient.
AB  - Peptostreptococcus ivorii, a recently described species of gram-positive
      anaerobic coccus, has so far rarely been found in human infections. The isolation
      of this anaerobe from a polybacterial skin abscess in a HIV-infected patient,
      which formed after antiretroviral therapy had been discontinued is reported.
      Local treatment led to the abscess healing without specific antibiotics. As the
      type strain was isolated from a mixed infected leg ulcer, Peptostreptococcus
      ivorii could play an important role in synergistic infections of the skin.

PMID- 16887656
TI  - Comparison of recovery of anaerobic bacteria using the Anoxomat, anaerobic
      chamber, and GasPak jar systems.
AB  - The Anoxomat system provides an automated evacuation-replacement technique to
      create an anaerobic or microaerophilic environment in a jar. We evaluated the
      Anoxomat system for the growth of obligate anaerobes and for the recovery of
      anaerobic organisms from clinical specimens, and compared its performance to that
      of an anaerobic chamber and the GasPak System. Of the 54 stock strains tested,
      the Anoxomat, the chamber, and the GasPak recovered 95%, 95% and 93% at 24 h,
      respectively. On 29 occasions (51%), the colonies on the Anoxomat plates were
      slightly larger than those in the chamber and on 17 (30%) occasions larger than
      the colonies on the GasPak jar plates. At 48 h, the Anoxomat, the chamber, and
      the GasPak recovered 93.5%, 94.4% and 88.9%, respectively; of 108 anaerobes
      isolated from 31 clinical specimens. Methylene blue indicators became decolorized
      (average of 10 tests) within 2 h inside the Anoxomat jars, 2 h 10 min inside the
      anaerobic chamber, and 2 h 30 min inside the GasPak jars.

PMID- 16887657
TI  - Characterization of beta-lactam-resistant Bacteroides fragilis isolates by use of
      PCR fingerprinting.
AB  - PCR fingerprinting was used for characterization of 35 beta-lactam-resistant
      Bacteroides fragilis strains isolated in Sweden and Hungary. Ten B. fragilis
      strains showed unique PCR fingerprints by use of the M13 core primer. Their main
      product was a DNA fragment with a length of 2000-bp which was absent in the other
      25 strains and the reference strain B. fragilis ATCC 25285. The 2000-bp fragment
      from four imipenem-resistant strains gave rise to positive reactions in a
      specific PCR for detection of ccrA. Printed by the T3B primer, five B. fragilis
      strains, including the imipenem-resistant strains showed unique PCR fingerprints.
      The investigated imipenem-resistant strains produced carbapenem-hydrolysing
      metallo-beta-lactamases. The study indicates that the unique PCR fingerprinting
      profiles shown in highly beta-lactam resistant B. fragilis strains are correlated
      to antimicrobial resistance. The PCR fingerprinting technique is a useful tool
      for differentiation of Bacteroides fragilis strains with high-level beta-lactam
      resistance.

PMID- 16887658
TI  - Persistence and multiplication of obligate anaerobe bacteria in amebae under
      aerobic conditions.
AB  - After co-cultivation of Mobiluncus curtisii, an obligate non-sporeforming
      anaerobe, with free living amebae from the Acanthamoeba spp. under aerobic
      conditions, internalization, multiplication and persistence of bacterial cells
      were established for at least 4-6 weeks. Under the same conditions and media
      without viable amebae, the cells of M. curtisii did not replicate and died in 4-7
      days. The infection of amebae occurred with 10 to 100 bacteria per ml of co
      cultivation media. In 7-14 days the amount of bacterial cells increased to
      1x10(5)-1x10(6) CFU/mL. Electron microscopic examinations revealed bacteria
      within vacuoles in the amebae and intracellular replication. These results
      suggest a previously undescribed mechanism for spread, replication and
      persistence of obligately anaerobe bacteria in the environment and new possible
      sources, reservoirs and transfer mechanisms of infections caused by obligate
      anaerobe bacteria.

PMID- 16887659
TI  - Degradation of phenol under meso- and thermophilic, anaerobic conditions.
AB  - Based on the results of preliminary studies on phenol degradation under
      mesophilic conditions with a mixed methanogenic culture, we proposed a
      degradation pathway in which phenol is fermented to acetate: Part of the phenol
      is reductively transformed to benzoate while the rest is oxidised, forming
      acetate as end product. According to our calculations, this should result in
      three moles of phenol being converted to two moles of benzoate and three moles of
      acetate (3 phenol + 2 CO2 + 3 H2O --> 3 acetate + 2 benzoate): To assess the
      validity of our hypothesis concerning the metabolic pathway, we studied the
      transformation of phenol under mesophilic and thermophilic conditions in relation
      to the availability of hydrogen. Hence, methanogenic meso- and thermophilic
      cultures amended with phenol were run with or without an added over-pressure of
      hydrogen under methanogenic and non-methanogenic conditions. Bromoethanesulfonic
      acid (BES) was used to inhibit methanogenic activity. In the mesophilic
      treatments amended with only BES, about 70% of the carbon in the products found
      was benzoate. During the course of phenol transformation in these BES-amended
      cultures, the formation pattern of the degradation products changed: Initially
      nearly 90% of the carbon from phenol degradation was recovered as benzoate,
      whereas later in the incubation, in addition to benzoate formation, the aromatic
      nucleus degraded completely to acetate. Thus, the initial reduction of phenol to
      benzoate resulted in a lowering of H2 levels, giving rise to conditions allowing
      the degradation of phenol to acetate as the end product. Product formation in
      bottles amended with BES and phenol occurred in accordance with the hypothesised
      pathway; however, the overall results indicate that the degradation of phenol in
      this system is more complex. During phenol transformation under thermophilic
      conditions, no benzoate was observed and no phenol was transformed in the BES
      amended cultures. This suggests that the sensitivity of phenol transformation to
      an elevated partial pressure of H2 is higher under thermophilic conditions than
      under mesophilic ones. The lack of benzoate formation could have been due to a
      high turnover of benzoate or to a difference in the phenol degradation pathway
      between the thermophilic and mesophilic cultures.

PMID- 16887660
TI  - Prevalence of CTGCAG recognizing restriction and modification systems in ruminal
      selenomonades.
AB  - Analysis of restriction and modification activities in natural population of
      Selenomonas ruminantium have revealed the prevalence of CTGCAG (Pst I
      isoschizomers) recognizing restriction and/or modification systems in these
      bacteria. Pst I isoschizomeric restriction endonucleases were detected in 4 out
      of 15 strains tested. In one strain, the Pst I isoschizomeric restriction system
      was accompanied by another restriction and modification system recognizing GAATTC
      sequence (Eco RI isoschizomer). Four other strains contained CTGCAG specific
      methylases which lacked cognate endo-nuclease activities. Presence of identical
      restriction and modification systems in both of subspecies of S. ruminantium, as
      well as the occurrence of Pst I isoschizomers in various combinations, indicate
      the possibility of horizontal transfer of genes coding for these systems.

PMID- 16887661
TI  - Isolation and characterization of heat-modifiable proteins from the outer
      membrane of Porphyromonas asaccharolytica and Acinetobacter baumannii.
AB  - Active porins were isolated and purified from the outer membranes of the gram
      negative anaerobic rod Porphyromonas asaccharolytica and the aerobic
      coccobacillus Acinetobacter baumannii. The porins from both bacteria appear to be
      monomers when isolated and purified. Both porins exhibited decreased mobility on
      SDS-PAGE after boiling for 10 min in the sample buffer. After heating, their
      molecular weight is estimated at 43 kDa while without heating they run as
      proteins with a molecular weight of approximately 37 kDa. Due to their
      characteristic heat-modifiability, these proteins were named HMP (heat-modifiable
      protein)-P. asaccharolytica and HMP-A. baumannii. Amino acid analysis revealed
      both porins to be hydrophilic proteins. These proteins have been shown to be
      active in transporting sugars when incorporated into liposomes. The permeability
      of both porins for L-arabinose was less than that produced by the porin of
      Escherichia coli B. Permeability to high molecular weight disaccharides was lower
      than for small monosaccharides. Western blot analysis did not reveal any
      antigenic cross reaction between HMP-A. baumannii and the HMP-P. asaccharolytica.
      The results obtained in this study confirm that although these heat-modifiable
      proteins are pore forming proteins and have similar activity they differ in their
      antigenicity.

PMID- 16887662
TI  - The Clostridium perfringens alpha-toxin.
AB  - The gene encoding the alpha-(cpa) is present in all strains of Clostridium
      perfringens, and the purified alpha-toxin has been shown to be a zinc-containing
      phospholipase C enzyme, which is preferentially active towards
      phosphatidylcholine and sphingomyelin. The alpha-toxin is haemolytic as a result
      if its ability to hydrolyse cell membrane phospholipids and this activity
      distinguishes it from many other related zinc-metallophospholipases C. Recent
      studies have shown that the alpha-toxin is the major virulence determinant in
      cases of gas gangrene, and the toxin might play a role in several other diseases
      of animals and man as diverse as necrotic enteritis in chickens and Crohn's
      disease in man. In gas gangrene the toxin appears to have three major roles in
      the pathogenesis of disease. First, it is able to cause mistrafficking of
      neutrophils, such that they do not enter infected tissues. Second, the toxin is
      able to cause vasoconstriction and platelet aggregation which might reduce the
      blood supply to infected tissues. Finally, the toxin is able to detrimentally
      modulate host cell metabolism by activating the arachidonic acid cascade and
      protein kinase C. The molecular structure of the alpha-toxin reveals a two domain
      protein. The amino-terminal domain contains the phospholipase C active site which
      contains zinc ions. The carboxyterminal domain is a paralogue of lipid binding
      domains found in eukaryotes and appears to bind phospholipids in a calcium
      dependent manner. Immunisation with the non-toxic carboxyterminal domain induces
      protection against the alpha-toxin and gas gangrene and this polypeptide might be
      exploited as a vaccine. Other workers have exploited the entire toxin as the
      basis of an anti-tumour system.

PMID- 16887663
TI  - Study of the caecal microflora of broiler ducks: a comparison with published data
      for chickens.

PMID- 16887664
TI  - Horace A. Barker (1907-) pioneer of anaerobic metabolism.
AB  - Dr Horace A. Barker was born and raised in California. He obtained his Ph.D. in
      chemistry from the University of California, Berkeley in 1933, and became a
      faculty member at the same campus in 1936. He devoted his research to the study
      of bacterial metabolism. His contributions include the detailed studies of
      various aspects of metabolism such as synthesis and oxidation of fatty acids,
      fermentation of amino acids and purines, and carbohydrate transformations. He
      isolated and determined the structure and function of some enzymes and coenzymes
      from bacteria. He also specifically described many anaerobic metabolic pathways.
      Dr Barker retired in 1976.

PMID- 16887665
TI  - Intrafamilial transmission of black-pigmented, putative periodontal pathogens.
AB  - Porphyromonas gingivalis and Prevotella intermedia are black-pigmented, putative
      periodontopathogenic bacteria considered to cause some forms of periodontal
      disease. Porphyromonas gingivalis and P. intermedia can be transmitted between
      humans and produce periodontal disease in susceptible hosts. In this article,
      studies using molecular typing methods for determining the transmission of black
      pigmented, putative periodontopathogens between family members are reviewed. As
      individuals living close to each other are more prone to transmit bacteria, the
      studies on transmission of periodontopathogens have been performed on family
      members. It has been shown that black-pigmented bacteria are not only transferred
      between spouses but also between parents and child. Since only a limited number
      of studies have been done, longitudinal and controlled studies should be carried
      out to elucidate further the transmittance potential of these bacteria.

PMID- 16887666
TI  - Taxonomic, phylogenetic, and ecological diversity of methanogenic Archaea.

PMID- 16887667
TI  - An examination of 'unidentified' Prevotella (formerly PINLO) using RAPD-PCR and
      partial 16S rRNA gene sequencing.
AB  - Prevotella intermedia- and Prevotella nigrescens-like organisms (PINLO) have been
      described as organisms which are phenotypically and biochemically similar to P.
      intermedia and P. nigrescens and the species P. pallens was created to include
      some of them. Other PINLO groups which do not fit the definition of P. pallens
      exist, and in this study these 'unidentified' Prevotella sp. were compared with
      P. corporis, P. intermedia, P. nigrescens and P. pallens using commercial
      identification kits, GLC, RAPD-PCR and partial 16S rRNA gene sequencing. The
      Rapid ID 32 A and the RapID ANA II system both identified all 'unidentified'
      Prevotella as P. intermedia. Similarly they gave this identification to all the
      species tested (with the exception of P. corporis using the RapID ANA II system)
      clearly demonstrating biochemical similarities. Gas liquid chromatography (GLC)
      analysis of the volatile end-products of fermentation could not distinguish
      between strains. RAPD-PCR using arbitrary primer L10 demonstrated intra-species
      homogeneity within PINLO strains with amplification profiles which differed from
      other Prevotella species tested. Cluster analysis of the amplification profiles
      confirmed species divisions and yielded a distinct 'unidentified' Prevotella
      cluster. Comparison of partial 16S rDNA sequences displayed 98% sequence
      similarity between the 'unidentified' Prevotella strains, although 2 strains, HST
      1156 and HST 2160 displayed 100% identity. The highest similarity between groups
      was seen between 'unidentified' Prevotella strains and P. corporis (approximately
      94% similarity). The DNA techniques used here confirm that 'unidentified'
      Prevotella strains are distinct from the other species of Prevotella tested,
      including P. pallens. Partial 16S rDNA sequence comparisons suggested a close
      relationship with P. corporis.

PMID- 16887668
TI  - Susceptibility of Prevotella intermedia/Prevotella nigrescens (and Porphyromonas
      gingivalis) to propolis (bee glue) and other antimicrobial agents.
AB  - Black-pigmented gram-negative anaerobes such as Porphyromonas gingivalis and
      Prevotella intermedia are suspected pathogens in adult periodontitis, whereas
      Prevotella nigrescens has been associated with health. Antimicrobial resistance
      among bacteria from this group has been reported in the past decade. This
      research aimed to evaluate and compare the susceptibility profile of 17 P.
      intermedia/P. nigrescens isolates recovered from patients with periodontitis and
      three reference strains to six antimicrobials, prescribed in dentistry in Brazil,
      and propolis (bee glue). The antimicrobial agents tested were tetracycline,
      penicillin, clindamycin, erythromycin, metronidazole, meropenem and six ethanolic
      extracts of propolis (EEPs) from Brazil. The reference strains P. gingivalis ATCC
      33277 and P. intermedia ATCC 25611 were used for determination of minimum
      bactericidal concentration (MBC) and for time-kill assay to the EEPs. All of the
      strains were susceptible to penicillin, erythromycin, meropenem, metronidazole
      and 95% of them (n=19) to tetracycline. Thirty six percent (n=7) of the P.
      intermedia/P. nigrescens strains tested were resistant to clindamycin. As for
      propolis activity, all strains were susceptible and the minimum inhibitory
      concentration values ranged from 64 to 256 microg/mL. For the reference strains
      P. gingivalis ATCC 33277 and Prevotella intermedia ATCC 25611 the MBC was 256
      microg/mL and death was observed within 3 h of incubation for P. gingivalis and
      within 6 h for P. intermedia. The action of propolis (bee glue) against suspected
      periodontal pathogens suggests that it may be of clinical value.

PMID- 16887669
TI  - Characterization of hemoglobin binding to Actinobacillus actinomycetemcomitans.
AB  - In this study, binding of hemoglobin to Actinobacillus actinomycetemcomitans was
      characterized. The ability of A. actinomycetemcomitans to utilize hemoglobin as
      an iron source was examined by growth studies. Although the bacterial growth was
      limited almost completely by adding 400 microM 2, 2'-dipyridyl to culture medium,
      addition of hemoglobin recovered the growth in a dose-dependent manner, revealing
      that hemoglobin can be utilized effectively as an iron source by A.
      actinomycetemcomitans. Binding of A. actinomycetemcomitans to hemoglobin was
      examined by dot-blot assay. Optimal hemoglobin-binding activity occurred at pH 6
      and activity under acidic conditions was found to be higher than that under
      alkaline conditions. Hemoglobin-binding activity was higher under anaerobic
      conditions than under aerobic conditions, and iron restriction in culture medium
      decreased the activity by 55%. Heat and trypsin treatments of the bacterial
      components reduced the activity by 28% and 60%, respectively. Globin inhibited
      the activity by 49%, while transferrin, lactoferrin and tested amino acids and
      sugars had little or no inhibitory effects. These results indicate that
      proteinaceous components of the bacterial cells may be involved in hemoglobin
      binding and that globin moiety of the hemoglobin molecule may be essential for
      the binding. In order to identify hemoglobin-binding proteins, the bacterial cell
      components extracted with n-octyl-beta-D-thioglucoside were subjected to SDS-PAGE
      and transferred to a nitrocellulose membrane. The membrane was incubated with
      hemoglobin and bound hemoglobin was detected with anti-hemoglobin antibodies.
      About 40- and 65-kDa proteins from A. actinomycetemcomitans reacted with
      hemoglobin. The 65-kDa protein was detected despite the iron concentration in
      culture medium, whereas expression of the 40-kDa protein was enhanced only when
      the organism was grown in iron-restricted culture medium. From these results, it
      is suggested that 40- and 65-kDa proteins of A. actinomycetemcomitans may be
      involved in hemoglobin binding.

PMID- 16887670
TI  - Taxonomy--General comments and update on taxonomy of Clostridia and Anaerobic
      cocci.
AB  - Since such things as sites of normal carriage, type and severity of infections
      produced, and antimicrobial susceptibility patterns may vary according to the
      particular species involved, accurate taxonomy for differentiation of species is
      important. For example, reclassification of the 'Bacteroides gracilis group'
      revealed that Sutterella wadsworthensis is actually responsible for the
      antimicrobial resistance seen in that group. With clostridia and anaerobic cocci,
      as with other taxa, there have been a number of recent changes in classification
      of existing taxa as well as description of novel taxa. It is important that both
      clinicians and microbiologists adapt quickly to new classification schemes and
      new taxa as soon as they are validated. For example, Peptostreptococcus is now
      restricted to the species P. anaerobius and five new genera have been created.
      There has also been significant reclassification of clostridia and new species of
      clostridia have also been described.

PMID- 16887672
TI  - Comparison of the post-antibiotic effect (PAE) induced by ceftizoxime,
      ceftriaxone, cefoxitin, ampicillin-sulbactam, and ticarcillin-clavulanate against
      selected isolates of Bacteroides fragilis and B. thetaiotaomicron.
AB  - The exposure of bacteria to various groups of antimicrobials at different
      concentrations can produce damage to the bacteria that persists even after
      removal of the antimicrobial agent. The post antibiotic effect (PAE) of beta
      lactams on aerobic gram-negative bacilli is relatively short (<1 h), however,
      little information is available regarding anaerobic gram-negative bacilli. We
      studied the PAE of ceftizoxime, ampicillin-sulbactam, ticarcillin-clavulanate,
      cefoxitin, and ceftriaxone against strains of Bacteroides fragilis and B.
      thetaiotaomicron at antimicrobial concentrations 4x, 8x, and 16x the MIC values
      using colony count determinations of treated and untreated cultures. Against B.
      fragilis H931, ceftizoxime-induced PAE values were 2 h, 3 h 24 min, and 11 h 36
      min at 4xMIC, 8xMIC, and 16xMIC while for the B. thetaiotaomicron isolates PAEs
      ranged from 2 h 27 min to 6 h 12 min at the same concentrations. Cefoxitin PAE
      values were 3 h 6 min and 2 h 18 min for the clinical isolates at 16xMIC and 3 h
      24 min and 1 h 12 min against the laboratory strains at 16xMIC respectively, and
      for ceftriaxone 1 h 12 min and 5 h 12 min, respectively, for the B.
      thetaiotaomicron D933 and B. fragilis H931 strains at 16xMIC. With ampicillin
      sulbactam, the longest PAE values were observed at 16xMIC with all the test
      isolates of B. fragilis and B. thetaiotaomicron. PAE values induced by
      ticarcillin-clavulanate overall were the shortest for the two clinical isolates.
      These studies indicate substantial PAE values for beta-lactams against selected
      anaerobes which may be an important factor in the dosing regimen of these test
      agents.

PMID- 16887671
TI  - Effect of pH and dose on the growth of gut bacteria on prebiotic carbohydrates in
      vitro.
AB  - The effect of pH and substrate dose on the fermentation profile of a number of
      commercial prebiotics was analysed in triplicate using stirred, pH and
      temperature controlled anaerobic batch culture fermentations, inoculated with a
      fresh faecal slurry from one of three healthy volunteers. Bacterial numbers were
      enumerated using fluorescence in situ hybridisation. The commercial prebiotics
      investigated were fructooligosaccharides (FOS), inulin, galactooligosaccharides
      (GOS), isomaltooligosaccharides (IMO) and lactulose. Two pH values were
      investigated, i.e. pH 6 and 6.8. Doses of 1% and 2% (w/v) were investigated,
      equivalent to approximately 4 and 8 g per day, respectively, in an adult diet. It
      was found that both pH and dose altered the bacterial composition. It was
      observed that FOS and inulin demonstrated the greatest bifidogenic effect at pH
      6.8 and 1% (w/v) carbohydrate, whereas GOS, IMO and lactulose demonstrated their
      greatest bifidogenic effect at pH 6 and 2% (w/v) carbohydrate. From this we can
      conclude that various prebiotics demonstrate differing bifidogenic effects at
      different conditions in vitro.

PMID- 16887673
TI  - Susceptibility trending of blood isolates of the Bacteroides fragilis group over
      a 12-year period to clindamycin, ampicillin-sulbactam, cefoxitin, imipenem, and
      metronidazole.
AB  - Numerous reports have described a steady overall increase in resistance among
      clinical isolates of the Bacteroides fragilis group to several antimicrobial
      agents, particularly clindamycin. Determination of resistance rates is
      significantly influenced by the number of isolates of each species within the B.
      fragilis group tested. Historically, the B. fragilis species has remained the
      most susceptible to most antimicrobials when compared to non-B. fragilis species.
      This study compares the effect of a gradually changing ratio of blood isolates of
      B. fragilis to non-B. fragilis species tested by broth micro-dilution over a 12
      year period on selected antimicrobial agents. In 1987, the ratio of blood
      isolates of B. fragilis to non-B. fragilis was 68% to 32%; in 1991 it was 59% to
      41%; and in 1999 it was 51% to 49%. Both metronidazole and imipenem showed the
      least changes because of their inherent high activity against all species. For
      clindamycin, decreases in susceptibility ranged from 84% to 64% for B. fragilis
      compared to 58% to 67% for non-B. fragilis species. Ampicillin-sulbactam showed a
      decrease in susceptibility in B. fragilis and non-B. fragilis species, but was
      highest in 1999 when the ratio of non-B. fragilis species was the highest.
      Overall resistance rates to cefoxitin varied from 8% to 25% during the testing
      years and was consistently higher among the non-B. fragilis species. These
      comparisons indicate that the ratio of B. fragilis group species isolated from
      the blood has changed over the last 12 years and has appreciably affected the
      resistance rates to some commonly used anti-anaerobic agents. Whether the noted
      changes in species isolation rates are a result of selective antibiotic pressure
      or other factors is yet to be determined.

PMID- 16887674
TI  - Bacteroides fragilis adherence to Caco-2 cells.
AB  - The ability of ten Bacteroides fragilis strains isolated from intestinal and non
      intestinal infections, normal flora and environment to adhere to human colon
      carcinoma cells, Caco-2, was examined. The adherence capacity varied among the
      strains tested from strongly adherent (76-100%) to non- or weakly adherent (0
      25%). Negative staining with Indian ink showed that all the strains were
      capsulated, although strain 1032 (strongly adherent and originated from
      bacteremia) had the highest rate of capsulated cells in the culture. All strains
      studied presented an electron-dense layer and no fimbrial structures in their
      surface after PTA negative staining. The analysis of the strains with ruthenium
      red showed the presence of an acidic polysaccharide and also surface vesicles in
      all of them. The strain 1032 presented an aggregative adherence pattern toward
      Caco-2 cells monolayers. It could be seen trapped by elongated microvilli and
      surrounded by extracellular material in the scanning electron microscope.
      Treatment with sodium periodate (100 mM/1 h) reduced significantly its adherence
      capacity and also the expression of an electron-dense layer and of the capsule,
      detected with PTA and Indian ink staining, respectively. We suggest that the
      capsular polysaccharide might mediate the adherence of the B. fragilis to Caco-2
      cells.

PMID- 16887675
TI  - Biotechnological potential of sulfate-reducing bacteria for transformation of
      nitrocellulose.
AB  - The biotransformation of NC by Desulfovibrio sp. was studied. The mass of NC was
      decreased by 4.9-9.3%. The rate of NC transformation was between 46 and 73 mg NC
      per mg of bacterial protein in 10 days. Moreover, N content (%N) in the remaining
      NC was reduced by 2-12%. The inhibitory effect of NC was clearly expressed when
      the growth of D. desulfuricans 1388 in lactate/sulfate medium was initiated. The
      growth rate of bacteria was 1.5-fold greater when NC was not added (0.074 and
      0.05 h(-1) respectively). The transformation of NC by D. desulfuricans was
      accompanied by the appearance of nitrate in the culture liquid, the amount of
      which reached the peak by the 8th day.

PMID- 16887676
TI  - Chitosan oligosaccharides, dp 2-8, have prebiotic effect on the Bifidobacterium
      bifidium and Lactobacillus sp.
AB  - In order to investigate the prebiotic potential of chitosan oligosaccharide
      (COS), prepared by enzymatic hydrolysis of fully deacetylated chitosan polymer,
      the effect of COS on bacterial growth was studied. The degree of polymerization
      (dp) of COS was determined by MALDI-ToF mass spectrometry, and the COS was found
      to be composed of dimer (33.6%), trimer (16.9%), tetramer (15.8%), pentamer
      (12.4%), hexamer (8.3%), heptamer (7.1%), and octamer (5.9%). The minimum
      inhibitory concentrations (MIC) of chitosan polymer against lactic acid bacteria
      and bifidobacteria were below 0.31%. However, this only applied to two strains,
      the other bacteria tested grew on MRS broth containing 5% COS. The effects of COS
      on the growth of bifidobacteria and lactic acid bacteria were compared with those
      of fructo-oligosaccharide (FOS). FOS was found to have a growth stimulatory
      effect on only three strains: Bifidobacterium bifidium, B. infantis and
      Lactobacillus casei. However, COS stimulated the growth of most Lactobacillus sp.
      and B. bifidium KCTC 3440. The amount of the growth and the specific growth rate
      of B. bifidium increased with increasing COS concentration. The cultivation time
      required to obtain maximum growth was reduced to about 25% in MRS broth
      supplemented with 0.2-0.4% COS. These results demonstrate that COS has
      considerable bifidogenic potential. Both cell growth and specific growth rates of
      L. brevis in MRS broth supplemented with 0.1% COS increased by 25%. The present
      study shows that COS stimulates the growth of some enteric bacteria, and that COS
      has potential use as a prebiotic health-food.

PMID- 16887677
TI  - Hydrogen metabolism in Desulfovibrio desulfuricans strain New Jersey (NCIMB 8313)
      -comparative study with D. vulgaris and D. gigas species.
AB  - This article aims to study hydrogen production/consumption in Desulfovibrio (D.)
      desulfuricans strain New Jersey, a sulfate reducer isolated from a medium
      undergoing active biocorrosion and to compare its hydrogen metabolism with two
      other Desulfovibrio species, D. gigas and D. vulgaris Hildenborough. Hydrogen
      production was followed during the growth of these three bacterial species under
      different growth conditions: no limitation of sulfate and lactate, sulfate
      limitation, lactate limitation, pyruvate/sulfate medium and in the presence of
      molybdate. Hydrogen production/consumption by D. desulfuricans shows a behavior
      similar to that of D. gigas but a different one from that of D. vulgaris, which
      produces higher quantities of hydrogen on lactate/sulfate medium. The three
      species are able to increase the hydrogen production when the sulfate became
      limiting. Moreover, in a pyruvate/sulfate medium hydrogen production was lower
      than on lactate/sulfate medium. Hydrogen production by D. desulfuricans in
      presence of molybdate is extremely high. Hydrogenases are key enzymes on
      production/consumption of hydrogen in sulfate reducing organisms. The specific
      activity, number and cellular localization of hydrogenases vary within the three
      Desulfovibrio species used in this work, which could explain the differences
      observed on hydrogen utilization.

PMID- 16887678
TI  - Nitric oxide production by murine spleen cells stimulated with lipopolysaccharide
      from Actinobacillus actinomycetemcomitans.
AB  - The aim of this study was to determine whether Actinobacillus
      actinomycetemcomitans lipopolysaccharide (LPS-A. actinomycetemcomitans) could
      induce murine spleen cells to produce nitric oxide (NO). Spleen cells derived
      from Balb/c mice were stimulated with LPS-A. actinomycetemcomitans or LPS from
      Escherichia coli for 4 days. The effects of N(G)-monomethyl-L-arginine (NMMA),
      polymyxin B, and cytokines (IFN-gamma and IL-4) on the production of NO were also
      assessed. The NO production from the carrageenan-treated spleen cells stimulated
      with LPS-A. actinomycetemcomitans or both LPS-A. actinomycetemcomitans and IFN
      gamma was determined. The carrageenan-treated mice were transferred with splenic
      macrophages and the NO production was assessed from the spleen cells stimulated
      with LPS-A. actinomycetemcomitans or LPS-A. actinomycetemcomitans and IFN-gamma.
      The results showed that NO production was detectable in the cultures of spleen
      cells stimulated with LPS-A. actinomycetemcomitans in a dose-dependent fashion,
      but was lower than in the cells stimulated with LPS from E. coli. The NO
      production was blocked by NMMA and polymyxin B. IFN-gamma up-regulated but IL-4
      suppressed the production of NO by the spleen cells stimulated with LPS-A.
      actinomycetemcomitans. The carrageenan-treated spleen cells failed to produce NO
      after stimulation with LPS-A. actinomycetemcomitans or both LPS-A.
      actinomycetemcomitans and IFN-gamma. Adoptive transfer of splenic macrophages to
      the carrageenan-treated mice could restore the ability of the spleen cells to
      produce NO. The results of the present study suggest that LPS-A.
      actinomycetemcomitans under the regulatory control of cytokines induces murine
      spleen cells to produce NO and that splenic macrophages are the cellular source
      of the NO production. Therefore, these results may support the view that NO
      production by LPS-A. actinomycetemcomitans-stimulated macrophages may play a role
      in the course of periodontal diseases.

PMID- 16887679
TI  - Bifidobacteria identification based on 16S rRNA and pyruvate kinase partial gene
      sequence analysis.
AB  - The lack of a simple and rapid identification system for Bifidobacterium species
      makes them difficult to use in industrial applications. To obtain valuable
      discriminating factor, we studied different strains, and human isolates by two
      molecular taxonomy methods. First method was based on chrono-differentiation. A
      metabolic gene (pyruvate kinase) was chosen to be used as a systematic
      discriminating factor. A comparison of about 40 pyruvate kinase protein sequences
      allowed us to synthesize two oligonucleotides that were able to amplify a
      fragment of this corresponding gene in our strains. Based on these partial
      pyruvate kinase gene sequences, several clusters could be identified. The second
      method used in this study was based on 16S rRNA sequences analysis. We compared
      sequences present in GenBank database, and this allowed to separate
      bifidobacteria species into different clusters. They were different from those
      obtained with partial pyruvate kinase gene sequences analysis. So, by combining
      both methods, we were able to identify our isolates, when only 10% of them could
      be strictly identified using the 16S rRNA method. Moreover, pyruvate kinase
      analysis allowed to differentiate very ambivalent groups such as B. animalis/B.
      lactis or B. infantis/B. longum, but created different clusters for B. infantis
      species group, questioning on the homogeneity of this species.

PMID- 16887680
TI  - An in vitro time-kill assessment of linezolid and anaerobic bacteria.
AB  - Linezolid is a novel oxazolidinone antibacterial agent active against
      staphylococci (including methicillin-resistant strains), enterococci (including
      vancomycin-resistant strains), streptococci (including penicillin-intermediate
      and -resistant Streptococcus pneumoniae), and other aerobic and facultative
      bacteria. The agent has also demonstrated activity against a broad spectrum of
      Gram-positive and Gram-negative anaerobic bacteria. Previous time-kill
      assessments have shown linezolid to be generally bacteriostatic against
      staphylococci and enterococci, and bactericidal against streptococci. In this
      study, an anaerobic glovebox technique was employed to conduct time-kill
      assessments for four strains of anaerobic Gram-positive, and seven strains of
      anaerobic Gram-negative bacteria. The time-kill experiment was performed using
      Anaerobe Broth medium. The drugs were tested at four-fold the minimum inhibitory
      concentration (MIC), or at the higher concentration of 8mg/L for linezolid, 2mg/L
      for clindamycin, and 8mg/L for metronidazole. Samples for viable count were taken
      at 0, 6, and 24h, and plated using the Bioscience International Autospiral DW.
      Exposure of samples to the aerobic environment during plating was held to less
      than 30min. Plates were counted after a 48h anaerobic incubation (37 degrees C).
      The species tested included Bacteroides fragilis (2), B. distasonis, B.
      thetaiotaomicron, Fusobacterium nucleatum, F. varium, Prevotella melaninogenica,
      Clostridium perfringens, Eubacterium lentum and Peptostreptococcus anaerobius
      (2). The activity of linezolid was compared to that of metronidazole and
      clindamycin, two standard anti-anaerobe agents. As expected, the control agents
      were very active in these assays. Metronidazole yielded log(10)CFU/mL reductions
      of 3.0 or greater for nine of ten strains; clindamycin yielded log(10)CFU/mL
      reductions of 2.0 or greater for six of 11 strains, and 3.0 or greater for three
      strains. Linezolid also produced significant in vitro killing in this model
      achieving log(10)CFU/mL reductions of 2.0 or greater for six of 11 strains, and
      3.0 or greater for four strains. The profile of activity was similar to that of
      clindamycin indicating that additional developmental studies of linezolid with
      anaerobic bacteria are warranted.

PMID- 16887681
TI  - Identification of Propionibacterium acnes by polymerase chain reaction for
      amplification of 16S ribosomal RNA and lipase genes.
AB  - Propionibacterium acnes belongs to the cutaneous flora and is present in
      sebaceous follicles. The fatty acids that are released from sebum triglycerides
      by the action of this bacterial lipase play an important role in the pathogenesis
      of acne vulgaris. P. acnes is also involved in postoperative disorders and
      opportunistic infections in immunosuppressed hosts. Recently, it has been
      proposed that P. acnes causes sarcoidosis. Therefore, rapid isolation and
      identification of P. acnes is important. This study evaluated the polymerase
      chain reaction (PCR) for the detection of the 16S rRNA and lipase genes of P.
      acnes. The PCR used to detect the 16S rRNA gene could amplify the gene of P.
      acnes, but not the genes of the other tested strains of P. avidum, P. granulosum,
      P. lymphophilum, P. jensenii, P. acidipropionici and P. thoenii. The PCR to
      detect the lipase gene of P. acnes, however, could amplify not only the gene of
      P. acnes but also that of P. avidum. The PCR product of this lipase gene was not
      found in the strains of the other species tested. Therefore, the organism that
      has both the 16S rRNA gene and lipase gene was identified as P. acnes, while the
      strain with the lipase gene but not the 16S rRNA gene of P. acnes was
      characterized as P. avidum. These findings were confirmed by the conventional
      biochemical tests including lipase activity. Furthermore, out of the seven
      clinical isolates from acne vulgaris, four were identified as P. acnes and three
      as P. avidum by the PCR method and biochemical tests. The combination of two PCR,
      one for the detection of the 16S rRNA and the other of lipase genes was shown to
      be an easier, faster and more accurate method to identify P. acnes and P. avidum
      than conventional methods.

PMID- 16887682
TI  - The micro-flora of the small bowel in health and disease.
AB  - The micro-flora of the proximal jejunum in healthy volunteers was compared with
      the micro-flora in patients with gastrointestinal symptoms suggestive of
      spontaneous bacterial overgrowth in the small intestine. Biopsies were taken
      distally to the ligament of Treitz with a Watson capsule. The samples were
      diluted and inoculated on selective and non-selective agar plates that were
      incubated aerobically and anaerobically. No major differences were found in the
      small jejunum micro-flora in healthy persons or in a heterogenous group of
      patients with gastrointestinal disorders. Oropharyngeal micro-organisms dominated
      the micro-flora in all subjects and colonic micro-organisms were found in low
      numbers in a few subjects from both groups. Streptococcus intermedius and
      Haemophilus parahaemolyticus were only found in the micro-flora of healthy
      subjects while Lactobacillus spp. was more frequently found in the samples from
      patients. Eight of 20 healthy subjects and five of 18 patients met the criterion
      of small intestinal overgrowth. Emerging evidence suggests that other factors are
      involved in the pathogenesis of the irritable bowel syndrome complex. There is a
      need for better understanding of the complicated interactions between the host
      and the endogenous micro-flora.

PMID- 16887683
TI  - Effect of heavy ion irradiation on DNA DSB repair in Methanosarcina barkeri.
AB  - Archaea are expected to be highly repair proficient since they survived the
      vicious onslaught of radiation damage at the time of their early appearance. The
      DNA double strand break repairing ability of mesophilic archaea Methanosarcina
      barkeri (DSM 804) was studied using (7)Li, (12)C and (16)O heavy ions and
      compared with that of (60)Co gamma-rays. They can repair double strand breaks
      and, as in eukaryotes, the nature as well as extent of induction and its
      subsequent repair were dependent on the linear energy transfer of the radiation
      source.

PMID- 16887684
TI  - Susceptibility of Fusobacterium nucleatum to killing by peroxidase-iodide
      hydrogen peroxide combination in buffer solution and in human whole saliva.
AB  - Some Gram-negative anaerobic bacteria have been associated with the infection of
      tooth supporting tissues, i.e. periodontitis. Of these bacteria, Fusobacterium
      nucleatum is sensitive to lactoperoxidase/myeloperoxidase-iodide-hydrogen
      peroxide system in vitro, but salivary concentrations of thiocyanate abolishes
      the bactericidality. These bacteria are located in periodontal pockets, on oral
      mucosa and in saliva. Although F. nucleatum most probably does not belong to the
      group of main periodontal pathogens, it sustains its proportion in the
      periodontal flora when gingivitis progresses to periodontitis. In this study, the
      sensitivity of F. nucleatum to different horseradish peroxidase-iodide-hydrogen
      peroxide combinations was tested both in buffer and in sterilized human whole
      saliva. Horseradish peroxidase was chosen because it does not bind thiocyanate at
      pH > or = 6. After 1h incubation at 37 degrees C, the cell viability was
      estimated by plate count and with flow cytometer using LIVE/DEAD BacLight kit
      (Molecular Probes, USA). In saliva, the horseradish peroxidase (50 microg/mL)
      iodide (2.5 mM)-hydrogen peroxide (2.5 mM) combination decreased the amount of
      viable bacteria to 37% compared to 85% in the control without any of the
      components when measured with flow cytometer. Replacement of buffer by saliva
      decreased the bactericidality of the peroxidase system. However, in buffer less
      iodide and hydrogen peroxide was needed to produce significant decrease in the
      number of viable bacteria when measured by plate count than with flow cytometer.
      Our study shows that horseradish peroxidase-iodide-hydrogen peroxide combination
      is able to kill F. nucleatum cells in saliva. Horseradish peroxidase-iodide
      hydrogen peroxide combination may be useful to diminish the degree of re
      colonization of periodontitis-associated bacteria after periodontal therapy and
      to inhibit the transmission of these bacteria via saliva.

PMID- 16887685
TI  - Biochemical analysis of neomycin-resistance in the methanoarchaeon
      Methanothermobacter thermautotrophicus and some implications for energetic
      processes in this strain.
AB  - Methanogenesis-driven ATP synthesis in a neomycin-resistant mutant of
      Methanothermobacter thermautotrophicus (formerly Methanobacterium
      thermoautotrophicum strain DeltaH) was strongly inhibited at both pH 6.8 and pH
      8.5 by the uncoupler 3,3',4',5 -tetrachlorosalicylanilide (TCS) in the presence
      of either 1 or 10 mM NaCl. The generation of a membrane potential in the mutant
      cells at pH 6.8 was also strongly inhibited by TCS in the presence of 1 or 10 mM
      NaCl. On the other hand, at pH 8.5 in the presence of 10mM NaCl, a protonophore
      resistant membrane potential of approximately 150 mV was found. These results
      indicate that in the mutant cells the process of energy transduction between
      methanogenesis and membrane potential generation is not impaired. In contrast to
      the wild-type strain, ATP synthesis in the mutant cells was driven by an
      electrochemical gradient of H(+) under alkaline conditions. Unlike wild-type
      cells, the mutant lacks the capacity to transduce an uncoupler-resistant membrane
      potential energy at pH 8.5 into ATP synthesis. Na(+)/H(+) exchange was comparable
      in the wild type and the mutant cells. Western blots of sub-cellular fractions
      with polyclonal antiserum reactive to the B-subunit of the halobacterial A-type
      H(+)-translocating ATPase confirmed the presence of A-type ATP synthase in the
      mutant cells. Furthermore, in the mutant cells a protein band of molecular mass
      about 45 kDa is absent but there was an abundant protein band at about 67 kDa.
      Based on the observed bioenergetic features of the mutant cells, neither the
      A(1)A(o) ATP synthase alone nor together with the Na(+)/H(+) antiporter seems to
      be responsible for ATP synthesis driven by sodium motive force. Rather, some
      other links between neomycin-resistance and failure of sodium motive force
      dependent ATP synthesis in the neomycin resistant mutant are discussed.

PMID- 16887686
TI  - Anti-oxidant defense of the cell Desulfovibrio desulfuricans B-1388.
AB  - The extracts of Desulfovibrio desulfuricans B-1388 cells, grown in anaerobic
      condition, display the superoxide dismutase activity. The maximum value of level
      activity (1.02 E/min/mg) is observed in the stationary phase of growth.
      Essentially the whole enzyme is localized in periplasmic fraction. Cells
      Desulfovibrio desulfuricans B-1388 do not show the catalase activity but contain
      active NADH- and NADPH-peroxidases. The activity of involved peroxidases depends
      on the physiological condition of culture.

PMID- 16887687
TI  - Colonic spirochetosis of colony-raised rhesus macaques associated with
      Brachyspira and Helicobacter.
AB  - Colonic spirochetosis is an inflammatory bowel disease that affects a broad range
      of hosts, including human and non-human primates. The disease in humans and non
      human primates is characterized by intimate attachment of the anaerobic
      spirochetes Brachyspira aalborgi and B. pilosicoli, and some unclassified
      flagellated microbes along the apical membrane of colonic enterocytes. Although
      the presence of spiral-shaped bacteria with single polar flagella and blunted
      ends in colonic spirochetosis is well established, the identities of many of
      these organisms is still unknown. Recently, Helicobacter species with a
      morphology similar to the flagellated bacteria present in colonic spirochetosis
      have been cultured from intestinal specimens obtained from rhesus macaques, some
      with idiopathic colitis. The purpose of the present study was to determine
      whether or not the flagellated bacteria seen in the colons of rhesus macaques
      with colonic spirochetosis are Helicobacter. The presence of flagellated bacteria
      alone (n=2) or together with spirochetes (n=1) in formalin-fixed and paraffin
      embedded colons of three rhesus macaques with the naturally occurring disease was
      demonstrated by immunohistochemical staining and ultrastructural examination.
      Total DNA extracted from affected and control intestinal specimens was amplified
      by polymerase chain reaction (PCR) using Helicobacter 16S rRNA gene-specific
      primers. Comparative nucleotide sequence analysis of PCR products cloned from
      positive reactions indicated that two distinct Helicobacter genomospecies were
      present either alone or in combination with Brachyspira in the colons of rhesus
      macaques with microscopic lesions indicative of colonic spirochetosis.

PMID- 16887688
TI  - Antibiotic susceptibility of clinically relevant anaerobes in Estonia from 1999
      to 2001.
AB  - At present little or no data is available regarding the resistance profiles of
      anaerobic bacteria in relation to the general usage of antibiotics. The objective
      of this study was to assess whether any potential relationship exists between the
      dynamics of antibiotic resistance of anaerobic bacteria and the consumption of
      antibiotics during the last 3 years within the Estonian population. In total, 416
      anaerobic isolates were investigated from various clinical samples. The anaerobes
      were isolated on Wilkins-Chalgren Agar, incubated in an anaerobic glove box and
      identified by standard methods. beta-lactamase negative strains were tested
      against metronidazole, clindamycin, benzylpenicillin and the positive strains
      were further tested against metronidazole, clindamycin, and ampicillin/sulbactam
      by E-tests. The results of the susceptibility tests were interpreted according to
      the current criteria of NCCLS. Data from the Estonian State Agency of Medicines
      was used to assess the antibiotic consumption rate in the population (Defined
      Daily Doses per 1000 inhabitants annually). The following species of anaerobes
      were isolated: B. fragilis group, Bacteroides sp., Fusobacterium sp.,
      Porphyromonas sp., Prevotella sp., Peptostreptococcus sp., in addition to various
      unidentified Gram-positive rods. Metronidazole resistance was not found among
      Gram-negative bacteria despite a relatively high consumption of this
      antimicrobial agent in Estonia. Only ampicillin/sulbactam demonstrated excellent
      in vitro activity against all anaerobes. Unexpectedly despite a relatively low
      rate of consumption of clindamycin a high rate of resistance to this agent
      occurred; a similar situation was noted for penicillin. In the present study we
      did not observe a relationship between the changes in antibiotic consumption
      (DDD/1000) rate and the resistance pattern of anaerobic bacteria to
      metronidazole, clindamycin, penicillin and ampicillin/sulbactam during a 3-year
      follow-up period. High resistance to penicillin among some species and also to
      clindamycin is similar to the global trend and argues for limited use of these
      antibiotics in empirical treatment. We would suggest that monitoring of local
      susceptibility pattern is necessary for the selection of initial empirical
      therapy.

PMID- 16887689
TI  - Acquired tetracycline and/or macrolide-lincosamides-streptogramin resistance in
      anaerobes.
AB  - In general bacterial antibiotic resistance is acquired on mobile elements such as
      plasmids, transposons and/or conjugative transposons. This is also true for many
      antibiotic resistant anaerobic species described in the literature. Of the 23
      different tetracycline resistant efflux genes identified, tet(B), tet(K), tet(L),
      and tetA(P) have been found in anaerobic species and six of the ten tetracycline
      resistant genes coding for ribosomal protection proteins, tet(M), tet(O),
      tetB(P), tet(Q), tet(W), and tet(32), have been identified in anaerobes. There
      are now three enzymes which inactivate tetracycline, of which the tet(X) has been
      identified in Bacteroides though is not functional under anaerobic growth
      conditions. A similar situation exists with the genes conferring macrolide
      lincosamide-streptogramin (MLS) resistance. Of the 26 rRNA methylase MLS
      resistant genes characterized, five genes; erm(B), erm(C), erm(F), erm(G), and
      erm(Q), have been identified in anaerobes. In contrast, no genes coding for MLS
      resistant efflux proteins or inactivating enzymes have been described in
      anaerobic species. This mini-review will summarize what is known about
      tetracycline and MLS resistance in genera with anaerobic species and the mobile
      elements associated with acquired tetracycline and/or MLS resistance genes.

PMID- 16887690
TI  - Clinical multicenter studies on surgical infections caused by Bacteroides
      fragilis.

PMID- 16887691
TI  - Review of the in vitro activity and potential clinical efficacy of levofloxacin
      in the treatment of anaerobic infections.
AB  - The activity of levofloxacin against aerobic bacteria has been well documented
      both in vitro and clinically, but its anaerobic activity has been infrequently
      studied. This new fluoroquinolone exhibits good in vitro activity (MIC(S) < or
      =2.0 microg/mL) against many anaerobic pathogens associated with acute sinusitis,
      bite wounds, and other soft-tissue infections. It is less active against
      Bacteroides fragilis (MIC (90)=2-4 microg/mL ) and has poor inhibitory activity
      against non-fragilis B. fragilis group species that are associated with
      gastrointestinal and genitourinary tract infections. Levofloxacin does not
      antagonize the in vitro activity of clindamycin and metronidazole and often
      provides additive or synergistic activity against anaerobic bacteria with these
      agents. In pharmacodynamic models, levofloxacin exhibits rapid bactericidal
      activity at 2-4 times the MIC of anaerobic bacteria. Prolonged killing is
      observed when the area-under-the concentration-time-curve to MIC ratio is greater
      than 40. In clinical efficacy trials, levofloxacin has been effective in the
      treatment of patients with gynecologic, skin and skin-structure, and bone
      infections involving anaerobic pathogens. Both micro-biologic and pharmacodynamic
      studies support further evaluations of levofloxacin in the treatment of selective
      mixed aerobic/anaerobic infections.

PMID- 16887692
TI  - Bacteriology of human bite wound infections.
AB  - This study was designed to define the bacteriology of infected soft-tissue wounds
      from human bites, and to compare this with the bacteriology of infected animal
      bites in humans as determined in previous studies. The specimens were collected
      from 57 patients presenting to emergency rooms at 12 locations around the
      country. Three hundred and eighty organisms were isolated (224 aerobes and 156
      anaerobes), for an average of 6.6 per specimen. The most prevalent anaerobes
      recovered were Prevotella spp. (34%), while streptococci comprised 44% of all
      aerobic organisms, over half of which were in the "Streptococcus milleri" group,
      particularly S. anginosus. The study demonstrated that the pathogens in human
      bite infections differ considerably from those present in animal bites.

PMID- 16887693
TI  - Porphyromonas asaccharolytica liver abscess.
AB  - The black pigmented Gram-negative anaerobes, Porphyromonas species, have been
      isolated from clinical specimens in cases of central nervous system, dental-oral,
      pleuropulmonary and genitourinary infections and bacteremia. Herein, we report an
      unusual case of liver abscess caused by Porphyromonas asaccharolytica that has
      not been previously reported.

PMID- 16887694
TI  - Susceptibility of hamsters to human pathogenic Clostridium difficile strain B1
      following clindamycin, ampicillin or ceftriaxone administration.
AB  - Clindamycin-treated hamsters are predictably susceptible to infection with
      pathogenic strains of Clostridium difficile. This animal model parallels most of
      the important aspects of human C. difficile associated disease (CDAD). In humans,
      almost any antibiotic may precipitate CDAD, but clindamycin, ampicillin and
      second-and third-generation cephalosporins are implicated most often. We studied
      the effect of ampicillin and ceftriaxone compared to clindamycin on the
      susceptibility of hamsters to challenge with C. difficile strain designated B1 by
      restriction endonuclease typing, an epidemic strain from one hospital. Hamsters
      were highly susceptible to CDAD following a single dose of clindamycin (30 mg/kg
      orogastrically) from 1 to 4 days when challenged with 100 colony-forming units
      (CFU) of spores of epidemic CD strain B1. Ampicillin was given orogastrically at
      60 mg/kg to groups of three hamsters that were challenged with 10000 CFU of CD
      strain B1 spores on days 1-4 following ampicillin. Hundred percent CDAD mortality
      occurred in all groups on each challenge day. Ceftriaxone, given
      intraperitoneally at 60 mg/kg, induced susceptibility to CDAD for a more limited
      time course and at a higher CD inoculum, producing 100% mortality when hamsters
      were challenged with 10000 CFU of CD strain B1 on day 1 following ceftriaxone,
      33% mortality at day 2, and no CDAD when challenged on days 3 and 4 following
      ceftriaxone. Hamsters are susceptible to CD infection for at least 4 days
      following ampicillin and clindamycin, but ceftriaxone has a shorter duration of
      susceptibility.

PMID- 16887695
TI  - Desulfovibrio capillatus sp. nov., a novel sulfate-reducing bacterium isolated
      from an oil field separator located in the Gulf of Mexico.
AB  - A new spirilloid sulfate-reducing bacterium designated strain MET2(T) (T=type
      strain), was isolated from a Mexican oil field separator. Electron microscopy
      revealed a Gram-negative cell wall consisting of a 150nm thick undulating outer
      membrane. Strain MET2(T) appeared singly or in long chains and was actively
      motile with a corkscrew-like motion. The isolate grew optimally at 40 degrees C,
      pH 7.4 and 3% NaCl in a medium containing lactate, thiosulfate and yeast extract.
      Sulfate, sulfite, thiosulfate, and elemental sulfur served as electron acceptors
      but not nitrate or fumarate. Lactate, pyruvate and H(2) (with acetate as carbon
      source) were used as electron donors. Pyruvate was fermented. Desulfoviridin and
      cyt c were present. The G+C content of the DNA was 58.7mol%. Phylogenetic
      analysis based on 16S rDNA sequencing showed that strain MET2(T) was a member of
      the genus Desulfovibrio with "D. gracilis" and D. longus being its closest
      relatives (similarities of 98.3% and 97.1%, respectively). However, DNA-DNA
      hybridization studies indicated poor homologies (values <70%) with both species.
      On the basis of genotypic, phenotypic, and phylogenetic characteristics, strain
      MET2(T) (=DSM14982(T)=CIP107483(T)) is proposed as the type strain of a new
      species, Desulfovibrio capillatus sp. nov. GenBank accession number for the 16S
      rDNA sequence for MET2(T) is AY176773.

PMID- 16887696
TI  - Antibiotic resistance among anaerobic Gram-negative bacilli: lessons from a
      French multicentric survey.
AB  - Temporal changes of antibiotic susceptibilities among anaerobes in France are
      followed in our laboratory since 1992. For Bacteroides strains, resistance
      increased from 1992 to 1998 for amoxicillin-clavulanic acid, cefotetan and
      clindamycin. The present study evaluates the situation in 2000 for 434 Gram
      negative anaerobic clinical isolates (obtained from 9 large university hospitals)
      by testing amoxicillin and ticarcillin alone or combined with clavulanic acid,
      cefoxitin, cefotetan, imipenem, clindamycin and metronidazole (using the NCCLS
      approved method for MIC determination. The main genera tested included
      Bacteroides (359 strains of the fragilis group), Prevotella (40 strains),
      Fusobacterium (23 strains) and miscellaneous species (8 strains). Resistance
      rates within the B. fragilis group were: amoxicillin-clavulanic acid 5.6%,
      ticarcillin 33%, ticarcillin-clavulanic acid 2%, cefoxitin 13%, cefotetan 44%,
      clindamycin 33%, imipenem 1% and metronidazole <1%, respectively. Only one strain
      of B. fragilis was resistant to metronidazole (MIC=64 mg/L); due to the presence
      of the nimA gene on the chromosome. Resistance to imipenem or metronidazole was
      only found among the B. fragilis species. These two former drugs excepted, B.
      fragilis was less resistant to antibiotics than the other species. beta-lactamase
      production was detected for 357/359 strains of the fragilis group, 26/40 stains
      of Prevotella and 3/23 strains of Fusobacterium. Dynamic changes of antibacterial
      resistance are occurring within the B. fragilis group: decreased resistance to
      amoxicillin-clavulanic acid, ticarcillin-clavulanic acid, imipenem while
      resistance for cefoxitin, cefotetan, clindamycin continues to increase. Regular
      antibiotic surveys are needed as a source of information to guide the empirical
      therapy of anaerobic infections.

PMID- 16887697
TI  - Clostridium difficile-associated diarrhea from a general hospital in Argentina.
AB  - Clostridium difficile is responsible for 15-25% of all cases of antibiotic
      associated diarrhea. The incidence of infection with this organism is increasing
      in hospitals worldwide, consequent to the widespread use of broad-spectrum
      antibiotics. Although the clinical and financial impact of nosocomial C.
      difficile infection is believed to be significant, only limited information is
      available on the importance of C. difficile as a cause of diarrhea in Argentina.
      The aim of the study was to evaluate the impact and diagnosis methods of CDAD
      from symptomatic patients in a general hospital from Argentina. Consecutive
      diarrheal stool samples from symptomatic patients from a General Hospital in
      Argentina were screened for toxigenic C. difficile between April 2000 and April
      2001. Toxins were detected in stools by the Premier Cytoclone A+B EIA. Each
      specimen was examined for toxigenic C. difficile strains by culture. From 104
      specimens, 40 (38.5%) [32 of 87 patients (36.8%)] were positive and 64 (61.5%)
      [55 of 87 patients (63.2%)] were negative by stool toxin assay and/or toxigenic
      culture. In 11 of 40 positives samples C. difficile toxins were detected only by
      toxigenic culture. Five (15.6%) patients presented with symptomatic recurrences.
      Toxin-negative strains were not isolated. This data indicates that the high
      prevalence of toxigenic strains of C. difficile is of concern in routine
      diagnostic testing for C. difficile toxins in our study population. Detection of
      toxins in stools by EIA, coupled with testing strains for toxigenicity only in
      those cases in which direct toxin assay produces negative results, may be a
      satisfactory strategy. CDAD is an emerging nosocomial problem in our hospital. It
      will be necessary to evaluate the epidemiology and measures to control nosocomial
      spread.

PMID- 16887698
TI  - Anaerobic seminal fluid micro-flora in chronic prostatitis/chronic pelvic pain
      syndrome patients.
AB  - We investigated the seminal micro-flora of 116 men. Eighty-four men had chronic
      prostatitis/chronic pelvic pain syndrome (CP/CPPS), and 34 of them were also
      leukocytospermic. Thirty-two asymptomatic men formed the control group. Micro
      organisms were found in all of the 116 seminal fluid specimens. More than 20
      different micro-organisms were found in both groups. Neisseria gonorrhoeae and
      Chlamydia trachomatis were not found. A high frequency of anaerobic bacteria was
      found in all groups (68-79%), and in most of the specimens, anaerobic micro
      organisms were equal to or outnumbered the aerobic strains. We found 1-8
      different micro-organisms in each semen sample, the total count of micro
      organisms ranged from 10(2) to 10(7)/mL of semen. Both parameters were
      significantly higher in leukocytospermic CP/CPPS (NIH IIIA category) patients
      (median=5 different micro-organisms; total median count 5 x 10(4)) than in the
      control group (median=3 different micro-organisms; total median count 10(3)). In
      the CP/CPPS patients, the prevalence and/or count of some opportunistic bacteria
      was higher than in the control group. To show that the micro-organisms do not
      originate from the urethra, first voided urine was also investigated in 17
      prostatitis patients and 15 controls. One patient had significantly fewer micro
      organisms (median 1 vs. 4) and a lower total count of micro-organisms (median
      10(2) vs. 10(4)/mL) in the first-catch urine than in the seminal fluid. We found
      only one third of the micro-organisms to be similar in urine and semen while
      anaerobic bacteria and some aerobic opportunists were infrequent in urine. Semen
      is a suitable specimen for the diagnosis of prostatitis.

PMID- 16887699
TI  - Effects of electron transport inhibitors on iron reduction in Aeromonas
      hydrophila strain KB1.
AB  - The aim of this study was to determine the influence of respiratory chain
      inhibitors upon iron (III) reduction in Aeromonas hydrophila strain KB1. Optimal
      conditions of the reduction process were established by determining the amount of
      biomass, optimal pH, temperature and substrate concentration. The obtained
      results allowed us to determine Hill equation coefficients (K(m)=1.45+/-0.18 mM;
      V(max)=83.40+/-2.70 microM/min, and h=0.7+/-0.03). The value of h points to
      Michaelis-like kinetics of the process. The substrate concentration used in our
      study was such as to allow the maximum iron reduction rate. The reaction was
      mesophilic. The participation of electron carriers in the iron reduction process
      was investigated using respiratory chain inhibitors. Rotenone and capsaicin were
      used to study Q sites of the respiratory chain complex I. Dicumarol was used as
      an inhibitor of the quinone loop, while quinacrine was used to inhibit alloxazine
      centers. Additionally, complex III inhibitors, such as antimycin A, myxothiazole
      and 2-heptyl-4-hydroxy-quinoline N-oxide (HQNO) were used. Azide was used to
      inhibit complex IV. The observed inhibition of iron reduction by rotenone and
      capsaicin may suggest the existence of Q sites in formate reductase, analogous to
      those in complex I. Inhibition of quinones, isoalloxazine centers and complex III
      suggests participation of these carriers in the electron transport during iron
      reduction. Lack of inhibition of iron reduction by azide suggests that complex IV
      does not participate in this process.

PMID- 16887700
TI  - A comparative analysis of two cDNA clones of the cellulase gene family from
      anaerobic fungus Piromyces rhizinflata.
AB  - Cellulase family and some other glycosyl hydrolases of anaerobic fungi inhabiting
      the digestive tract of ruminants are believed to form an enzyme complex called
      cellulosome. Study of the individual component of cellulosome may shed light on
      understanding the organization of this complex and its functional mechanism. We
      have analysed the primary sequences of two cellulase clones, cel5B and cel6A,
      isolated from the cDNA library of ruminal fungus, Piromyces rhizinflata strain
      2301. The deduced amino acid sequences of the catalytic domain of Cel5B, encoded
      by cel5B, showed homology with the subfamily 4 of the family 5 (subfamily 5(4))
      of glycosyl hydrolases, while cel6A encoded Cel6A belonged to family 6 of
      glycosyl hydrolases. Phylogenetic tree analysis suggested that the genes of
      subfamily 5(4) glycosyl hydrolases of P. rhizinflata might have been acquired
      from rumen bacteria. Cel5B and Cel6A were modular enzymes consisting of a
      catalytic domain and dockerin domain(s), but not a cellulose binding domain. The
      occurrence of dockerin domains indicated that both enzymes were cellulosome
      components. The catalytic domain of the Cel5B (Cel5B') and Cel6A (Cel6A')
      recombinant proteins were purified. The optimal activity conditions with
      carboxymethyl cellulose (CMC) as the substrate were pH 6.0 and 50 degrees C for
      Cel5B', and pH 6.0 and 37-45 degrees C for Cel6A'. Both Cel5B' and Cel6A'
      exhibited activity against CMC, barley beta-glucan, Lichenan, and oat spelt
      xylan. Cel5B' could also hydrolyse p-nitrophenyl-beta-d-cellobioside, Avicel and
      filter paper while Cel6A' did not show any activity on these substrates. It is
      apparent that Cel6A' acted as an endoglucanase and Cel5B' possessed both
      endoglucanase and exoglucanase activities. No synergic effect was observed for
      these recombinant enzymes in vitro on Avicel and CMC.

PMID- 16887701
TI  - Heat and acid tolerance of Clostridium novyi Type A spores and their survival
      prior to preparation of heroin for injection.
AB  - Clostridium novyi Type A was implicated as a cause of an outbreak of serious
      illness and deaths among drug users in the United Kingdom who injected heroin
      intramuscularly. A contaminated batch of heroin was believed to be the source of
      infection. To test the ability of the outbreak strain to survive certain
      processes associated with heroin use, it was tested for its ability to survive a
      range of temperature and pH and the process used in preparation of "street"
      heroin for injection. C. novyi spores survived temperatures of up to 100 degrees
      C in aqueous solution for 5 min and survived pH 2.0 at ambient temperatures for a
      similar time. However, a combination of low pH and raised temperatures reduced
      survival times. An experiment reconstructing the "street" preparation of heroin
      demonstrated that any C. novyi spores present would survive this process and thus
      be capable of initiating infection under the right conditions.

PMID- 16887702
TI  - In vitro effects of Clostridium perfringens type D epsilon toxin on water and ion
      transport in ovine and caprine intestine.
AB  - Clostridium perfringens type D produces enterotoxaemia in sheep, goats and other
      animals. The disease is caused by C. perfringens epsilon toxin, and while
      enterotoxaemia in goats is usually characterized by enterocolitis, the disease in
      sheep is characterized by systemic lesions (such as lung and brain oedema) with
      minor and inconsistent changes observed in the intestine. A possible explanation
      for these differences is that epsilon toxin is more promptly absorbed by sheep
      than goat intestine. In an attempt to clarify this, we examined the in vitro
      effects of epsilon toxin on sheep and goat intestine. Pieces of intestinal mucosa
      from recently slaughtered animals were mounted in a modified Ussing-type chamber
      where net water flux (J(w)), short-circuit current (I(sc)) and tissue conductance
      (G(t)) were simultaneously recorded. After 70 min of incubation with epsilon
      toxin a reduction in absorptive J(w) and an increase in I(sc) and G(t) were
      observed in colonic tissues of both sheep and goats, but no alterations were
      registered in the ileum of either species. These in vitro results show that
      epsilon toxin affects the transport function of the colonic mucosa but it does
      not seem to produce any transport alteration in the ileum mucosa.

PMID- 16887703
TI  - Characterization of the predominant anaerobic bacterium recovered from digital
      dermatitis lesions in three Michigan dairy cows.
AB  - Digital dermatitis is a superficial epidermatitis of the feet of cattle. Data
      from previous work suggest that spirochaetes, Campylobacter spp., and Bacteroides
      spp. may be important in the disease, but the etiology of this disease is not
      entirely clear. Tissue samples collected from digital dermatitis lesions in three
      Holstein-Friesian cows from a Michigan dairy yielded a predominant colony type
      when incubated anaerobically on blood agar at 35 degrees C for 24-48 h. The
      isolate was a non-flagellated Gram-negative rod, 7 microM long and <0.5 microM
      wide; its growth was strictly anaerobic and resulted in slight ss-hemolysis on
      blood agar; 16S rRNA gene sequence analysis indicated it belonged to the
      cytophoga-flexibacter-bacteroides phylum. The finding that this bacterium was the
      predominant anaerobe recovered from digital dermatitis lesions suggests it may be
      involved in the digital dermatitis disease process.

PMID- 16887704
TI  - Therapeutic efficacy of moxifloxacin in a murine model of severe systemic mixed
      infection with Escherichia coli and Bacteroides fragilis.
AB  - The therapeutic efficacy of moxifloxacin was studied in an experimental murine
      model of a systemic aerobic/anaerobic mixed infection and compared to therapies
      with either imipenem or ciprofloxacin plus metronidazole. Groups of 20 mice each
      were intravenously (iv) infected with approximately 2.5 x 10(6) colony forming
      units (CFU) of Escherichia coli and 2 x 10(7)CFU of Bacteroides fragilis. Iv
      therapy was started 24 h post-infection (pi) with either moxifloxacin, imipenem,
      or ciprofloxacin plus metronidazole, for 3 days. A control group of 20 mice was
      left untreated. Survival rate at day seven pi was recorded, mice were then
      sacrificed and bacterial organ contents of livers and kidneys were determined.
      All mice treated survived at day seven, while six animals of the untreated group
      died. B. fragilis was not detected in any of the treated mice. E. coli was found
      in two of the moxifloxacin-treated mice and in two and five of the ciprofloxacin
      plus metronidazole and imipenem-treated animals, respectively. The results
      indicate that a therapy of severe mixed aerobic/anaerobic infections with
      moxifloxacin might be feasible and possibly be as efficacious as current therapy
      regimens with ciprofloxacin plus metronidazole or imipenem.

PMID- 16887705
TI  - Clostridium difficile and enterotoxigenic Bacteroides fragilis strains isolated
      from patients with antibiotic associated diarrhoea.
AB  - From the fecal samples of 332 patients with a clinical diagnosis of antibiotic
      associated diarrhoea (AAD), 131 Clostridium difficile strains were isolated. For
      detection of toxin A in the isolated strains the enzymatic immunoassay was used.
      The cytopathic effect was determined on McCoy cell line. PCR was used for the
      detection of non-repeating and repeating sequences of toxin A gene and non
      repeating sequences of toxin B gene. One hundred and six isolated C. difficile
      strains were TcdA(+)TcdB(+), 10 strains TcdA(-)TcB(+) and 15 were non-toxigenic
      TcdA(-)TcdB(-). Out of the same fecal samples 50 Bacteroides fragilis strains
      were isolated. All B. fragilis strains were tested in PCR reaction for
      fragilysine gene detection (bft). In 9 strains (18%) this gene was detected and
      the strains could be assumed as enterotoxigenic Bacteroides fragilis (ETBF). In 4
      fecal samples toxigenic C. difficile (TcdA(+)TcdB(+)) was found simultaneously
      with ETBF. One sample contained C. difficile (TcdA(-)TcdB(+)) and ETBF. Out of 4
      fecal samples only ETBF was isolated. The cytotoxicity of ETBF strains was tested
      on HT29/C1 human colon carcinoma cell line. The cytotoxicity titer in the range
      of 20 and 80 was observed.

PMID- 16887706
TI  - The complex oxidative stress response of Bacteroides fragilis: the role of OxyR
      in control of gene expression.
AB  - Gram-negative anaerobes in the genus Bacteroides are the predominant members of
      the GI-tract microflora where they play an important role in normal intestinal
      physiology. Bacteroides spp. also are significant opportunistic pathogens
      responsible for an array of intra-abdominal and other infections. Bacteroides
      fragilis is the most common anaerobic pathogen and it possesses virulence factors
      such as a capsule and neuraminidase that contribute to its success as a pathogen.
      Infection occurs when organisms escape from the anaerobic colon to aerobic sites
      such as the peritoneum where O(2) concentrations average 6%. Thus in addition to
      the classic virulence factors, resistance to oxidative stress is essential and
      may be involved in the initiation and persistence of infection. In fact, B.
      fragilis is highly O(2) tolerant, surviving extended periods (>24h) of O(2)
      exposure without a significant affect on viability. For protection against this
      oxidative stress B. fragilis mounts a complex physiological response that
      includes induction of >28 proteins involved in detoxification of oxygen radicals,
      protection of macromolecules, and adaptive physiology. One experimental strategy
      used to characterize this oxidative stress response is the direct detection of
      genes and proteins induced during exposure to O(2) or H(2)O(2). The methods
      employed have included RNA differential display to capture unique mRNA
      transcripts produced during oxidative stress, and native or 2D-gel
      electrophoresis to isolate and identify newly formed stress-induced proteins.
      Using these and other approaches a wide array of genes induced by oxidative
      stress have been discovered. These include genes for catalase, superoxide
      dismutase, thioredoxin-peroxidase, p20-peroxidase, cytochrome c peroxidase, Dps,
      alkyl hydroperoxidase, aerobic ribonucleotide reductase, ruberythrin, starch
      utilization, aspartate decarboxylase, and an RNA binding protein. The genes
      encoding these activities fall into three regulatory classes: (1) induced by O(2)
      only, (2) induced by H(2)O(2) only, and (3) induced by either O(2) or H(2)O(2).
      Such a complex regulatory response will likely involve multiple regulators. Thus
      far one regulator has been identified, OxyR, which controls a subset of the class
      3 genes that are induced by either O(2) or H(2)O(2). OxyR responds rapidly to
      oxidative stress and transcriptional analyses have shown that OxyR-controlled
      genes are activated by as little as 0.5% O(2) or 10 microM H(2)O(2). Maximal
      expression of most OxyR regulon genes was reached at 50 microM H(2)O(2) and 2%
      O(2). These oxidant concentrations are similar to environmental levels that would
      be experienced by the organisms in tissues outside of the colon suggesting that
      the OxyR regulon would be induced during the course of an infection.

PMID- 16887707
TI  - Analysis of 16S rDNA reveals bacterial shift during in vitro fermentation of
      fermentable carbohydrate using piglet faeces as inoculum.
AB  - In vitro fermentation of sugar beet pulp (SBP) was carried out to determine which
      bacterial species would be enriched by use of this carbohydrate source. Faeces
      from four weaning piglets as a source of inoculum was also compared. The
      microbial diversity of the prominent bacteria before and after this in vitro
      fermentation was analysed using denaturing gradient gel electrophoresis (DGGE) of
      PCR amplicons of 16S rDNA. Before fermentation, the DGGE profiles showed
      differences between cultures inoculated with faeces from different piglets,
      though some bands were common to all piglets. After fermentation of SBP, three
      dominant bands appeared, of which two bands appeared in all samples and one for
      both replicates of one piglet. Sequences of the corresponding 16S rDNA of two
      bands showed 92% similarity to Eubacterium eligens and 96% similarity to
      Lachnospira pectinoschiza, and that of the third band 95% to L. pectinoschiza.

PMID- 16887708
TI  - Development of bacterial and bifidobacterial communities in feces of newborn
      babies.
AB  - Microbial 16S rDNA from babies' fecal samples were amplified by PCR, and analysed
      by denaturing gradient gel electrophoresis (DGGE), cloning and sequencing. PCR
      DGGE profiles were used to follow in time the colonization of the intestine by
      bacteria. Four healthy babies, one baby who received antibiotics and their
      parents participated to the present study to determine the extent to which
      administration of antibiotics can modify the bacterial colonization of neonatal
      human gut and verify the influence of parental factors on the formation of the
      fecal bacterial community. In the healthy babies, Escherichia coli or bacteria
      belonging to Clostridium spp. were the initial colonizers rapidly followed by
      Bifidobacterium, Bacteroides, Clostridium, Streptococcus, Enterococcus and
      Actinomyces. Bifidobacterium species appeared already after five days in the
      breast-fed babies while there was a delay in the baby who received a formula
      based diet during only one day after birth. In each baby two or three
      bifidobacterial species including B. infantis were found. The observed variations
      in species were not associated with the feeding changes. The comparison of DGGE
      profiles of the babies and their parents patterns showed bands with equal
      migration suggesting a vertical transmission determined by genetic and
      environmental factors. The brief appearance of pioneer bacteria determined as
      being E. coli and Enterococcus spp. in the profile from the baby under antibiotic
      therapy, was succeeded by a small stable community consisting of Ruminococcus
      species. No Bifidobacterium sequences were detectable in this antibiotic-treated
      baby in spite of a partly breast-milk diet.

PMID- 16887709
TI  - Mixed culture fermentation studies on the effects of synbiotics on the human
      intestinal pathogens Campylobacter jejuni and Escherichia coli.
AB  - Batch and continuous culture anaerobic fermentation systems, inoculated with
      human faeces, were utilised to investigate the antimicrobial actions of two
      probiotics, Lactobacillus plantarum 0407, combined with oligofructose and
      Bifidobacterium bifidum Bb12, combined with a mixture of oligofructose and xylo
      oligosaccharides (50:50 w/w) against E. coli and Campylobacter jejuni. In batch
      fermenters, both E. coli and C. jejuni were inhibited by the synbiotics, even
      when the culture pH was maintained at around neutral. In continuous culture C.
      jejuni was inhibited but the synbiotic failed to inhibit E. coli. Although no
      definitive answer in addressing the mechanisms underlying antimicrobial activity
      was derived, results suggested that acetate and lactate directly were conferring
      antagonistic action, rather than as a result of lowering culture pH. In the
      course of the study culturing and fluorescent in situ hybridisation (FISH)
      methodologies for the enumeration of bacterial populations were compared.
      Bifidobacterial populations were underestimated using plating techniques,
      suggesting the non-culturability of certain bifidobacterial species.

PMID- 16887710
TI  - Anaerobic bacteria cultured from the tongue dorsum of subjects with oral malodor.
AB  - The bacteria on the dorsum of the tongue are the most frequent cause of oral
      malodor; however, the bacterial flora of the tongue has not been well defined.
      Although recent studies have used DNA probes to detect the presence of certain
      periodontal pathogens, cultural studies have been limited because of the
      complexity of the flora of the tongue dorsum. The purpose of this study was to
      grow and to identify maximum numbers of capnophylic Gram-negative bacilli and
      anaerobic micro-organisms by culturing tongue samples on to several selective and
      non-selective media. The most frequently isolated species included
      Peptostreptococcus anaerobius, Collinsella aerofaciens, Eubacterium group,
      Actinomyces spp., Eikenella corrodens, Veillonella spp., Fusobacterium nucleatum,
      pigmented Prevotella spp. and Selenomonas spp. Reported for the first time are
      Actinomyces turicensis, Collinsella aerofaciens, Eubacterium saburreum, E.
      timidum, Prevotella tannerae, Campylobacter concisus, Campylobacter mucosalis,
      Leptotrichia buccalis, Selenomonas flueggei, and Centipeda periodontii. Species
      not previously reported in studies that used only molecular techniques were
      identified in the present study.

PMID- 16887711
TI  - Antimicrobial susceptibility and strain prevalence of Korean vaginal
      Lactobacillus spp.
AB  - One hundred eight vaginal lactobacilli were isolated from Korean women and
      characterized in terms of their antibiotics susceptibility and PCR-RFLP
      (polymerase chain reaction-restriction fragment length polymorphism) pattern. The
      in vitro antibiotics susceptibilities of 108 vaginal isolates to 13 antimicrobial
      agents were determined by broth dilution method based on NCCLS reference
      protocol. High rates of resistance were demonstrated for gentamicin, kanamycin,
      metronidazole, and streptomycin whereas all the isolates were susceptible to
      erythromycin. The concentrations of gentamicin, kanamycin, metronidazole,
      streptomycin, and erythromycin at which 90% of the vaginal isolates were
      inhibited (MIC90) were 100, 200, >200, 200 and 0.39 microg/mL, respectively. For
      molecular identification, PCR-RFLP analysis was employed where the 16S rDNA was
      amplified by PCR and the PCR products were digested with 8 different restriction
      endonucleases prior to being electrophoresed in agarose gels. Based on PCR-RFLP
      results, approximately half of the isolates were identified as Lactobacillus
      crispatus. Several isolates were further identified by DNA sequence analysis of
      their 16S rDNA.

PMID- 16887712
TI  - E-test antibiotics susceptibility of strict anaerobic bacteria.
AB  - The E-test is convenient for testing susceptibility of anaerobes. From September
      1998 to September 1999, 194 strains (105 Gram-positive bacteria, 89 Gram-negative
      bacteria) of clinically relevant samples were tested against five antibiotics
      benzylpenicillin, amoxicillin-clavulanic acid, clindamycin, metronidazole and
      imipenem on blood agar plates. Resistance to benzyl penicillin is widespread and
      Gram-negative bacteria and resistance to amoxicillin-clavulanic acid is
      exceptional. Metronidazole is very effective against anaerobes except non-spore
      forming aerotolerant Gram-positive rods and Peptostreptococcus micros.

PMID- 16887713
TI  - Fusobacterium necrophorum septicemia following Epstein-Barr virus infectious
      mononucleosis.
AB  - We report herein a case of a 20-year-old previously healthy man who presented, 25
      days after the onset of clinically and serologically confirmed Epstein-Barr virus
      (EBV) infectious mononucleosis, Fusobacterium necrophorum septicemia. The
      diagnosis of postanginal septicemia was confirmed by repeated demonstration of
      fusiform, obligate anaerobic, Gram-negative bacilli in anaerobic blood cultures,
      identified as F. necrophorum 15 days after admission. This case report aims at
      underlining the need of taking into consideration the possibility of severe
      Fusobacterium septicemia in previously healthy patients following EBV infectious
      mononucleosis in order to prevent increased mortality and morbidity.

PMID- 16887714
TI  - Binary toxin producing Clostridium difficile strains.
AB  - Clostridium difficile produces three toxins, TcdA, TcdB and CDT. TcdA and TcdB
      are single-stranded molecules acting as glucosyltransferases specific for small
      GTPases. CDT is an actin specific ADP-ribosylating binary toxin
      characteristically composed of two independent components, enzymatic CDTa (48
      kDa) and binding CDTb (99 kDa). The cdtA and cdtB genes were sequenced in two CDT
      positive strains of C. difficile (CD 196 and 8864) and at least two CDT-negative
      strains with truncated form of binary toxin genes are known (VPI 10463 and C.
      difficile genome strain 630). The prevalence of binary toxin producing strains is
      estimated to be from 1.6% to 5.5%, although a much higher proportion has been
      reported in some studies. The role of the binary toxin as an additional virulence
      factor is discussed.

PMID- 16887715
TI  - Occurrence of Clostridium difficile in fecal samples of HIV-infected children in
      Poland.
AB  - The prevalence of Clostridium difficile and its toxins (A and B) in HIV-positive
      children in Poland was investigated in a group of 18 children, aged 6 months to 8
      1/2 years. Stool samples were tested using an antigen detection method for toxin
      A/B, cytotoxicity-neutralization and culture. In 3 cases (17%) C. difficile
      toxins were detected in both stool samples and strains recovered from culture.
      The three strains isolated were shown by PCR methods to contain toxins A and B
      genes. All children had been treated previously with antimicrobial and antiviral
      agents. All three C. difficile-positive children had mild diarrhea that resolved
      without specific therapy. Further studies involving a large number of children
      and molecular analyses of isolated C. difficile strains are necessary to
      determine the frequency and rate of carriage of C. difficile strains among HIV
      positive children in Poland.

PMID- 16887716
TI  - Honey consumption in the state of Sao Paulo: a risk to human health?
AB  - Infantile botulism was recognized in 1976 as a paralyzing disease caused by the
      ingestion of viable spores that would germinate and colonize the intestinal tract
      of infants, with local production and absorption of Clostridium botulinum toxin.
      The possible origins of botulinic spores are dust and honey, which has been
      identified as a dietary risk factor for infantile botulism. The objectives of the
      present study were to investigate 100 honey samples obtained in the state of Sao
      Paulo (Brazil) in terms of incidence of botulinic spores and of microbiologic
      quality, in agreement with Decree 367/9. All 100 samples analysed were negative
      for the presence of Salmonella, Shigella, total coliforms. C. botulinum spores
      were present in 3 samples (3%) and molds and yeasts, in 64 samples (64%), but
      only 25 (25%) exceeded established criteria, with counts ranging from zero to 1.5
      x 10(5)CFU/g. The presence of small sporogenic Gram-positive rods was observed in
      42 (42%) of the 100 samples tested but these bacteria were not identified.

PMID- 16887717
TI  - Characterisation and subcellular localisation of the GroEL-like and DnaK-like
      proteins isolated from Fusobacterium nucleatum ATCC 10953.
AB  - Fusobacterium nucleatum is associated with periodontitis in humans, and is a
      central member of the dental biofilm. Heat shock proteins (HSPs) of many
      different bacteria have been considered to play important roles during
      inflammations and infections. We have identified and characterised the HSP60 and
      HSP70, the Escherichia coli GroEL and DnaK homologues, respectively, in F.
      nucleatum ATCC 10953. The N-terminal 22 amino acid residues of HSP60 exhibited up
      to 63.6% identity with members of the HSP60 heat shock protein family of some
      selected bacterial species, while the N-terminal of 25 residues of HSP70 revealed
      up to 80% identity with members of the HSP70 family. The subcellular localisation
      of HSP60 and HSP70 was analysed by immunoblotting of bacterial cell fractions and
      immunoelectron microscopy of whole cells. HSP60 and HSP70 were localised in the
      cytosol, associated with membranes and extracellular fractions. These results are
      consistent with localisation for HSPs found in other micro-organisms, which
      further lead to the suggestion of a potential role in the pathogenesis of
      infectious diseases.

PMID- 16887718
TI  - Travelling to the Commonwealth games, Melbourne, Australia.

PMID- 16887719
TI  - Threats to international travellers posed by tick-borne diseases.
AB  - To date, 14 tick-borne diseases have been reported in international travellers,
      the majority of cases being Lyme borreliosis caused by Borrelia burgdorferi sensu
      lato in North America and Eurasia, African tick bite fever caused by Rickettsia
      africae in sub-Saharan Africa and eastern Caribbean, and Central European
      encephalitis caused by tick-borne encephalitis virus in Europe. The clinical
      presentation is frequently non-specific, and tick-borne diseases should always,
      in the absence of other likely diagnoses, be suspected in travellers with flu
      like symptoms following a recent visit to tick-infested areas. Feasible
      microbiological diagnostic tests are widely unavailable, at least outside areas
      of endemicity where many infected travellers present. Empiric treatment with
      doxycycline should be considered in suspected cases of tick-borne bacterial
      diseases. Since ecotourism and adventure travel are increasingly popular
      worldwide, the incidence of travel-associated tick-borne diseases is likely to
      increase in the future.

PMID- 16887720
TI  - Clinical features and diagnosis of 42 travellers with cutaneous leishmaniasis.
AB  - BACKGROUND: Leishmania species that occur within different geographical areas may
      cause different clinical manifestations, virulence and drug sensitivity.
      Patients/Methods. All patients with a clinical diagnosis of cutaneous
      leishmaniasis seen at the Hospital for Tropical Diseases from 1997 to 2000 were
      identified and clinical details recorded onto a database, with emphasis on
      clinical presentation, risk factors, travel history and laboratory diagnosis.
      RESULTS: Forty-two patients were identified, 23 of whom had travelled to New
      World and 19 to Old World countries. Clinical presentation typically consisted of
      a single nodule with ulceration. In 50% infection was caused by L. (Viannia)
      braziliensis. PCR was performed in specimens from 34 patients and species
      identification was possible in 32 cases (sensitivity 94%), the two PCR negative
      patients had amastigotes demonstrated by histology and culture. Patients were
      treated with established therapies. Seventy one percent were cured by treatment,
      12% had a spontaneous cure, 7% were lost to follow-up and the remaining 10%
      required a second-line therapy. No relapses were reported during a mean follow-up
      period of 27 months. CONCLUSIONS: Our study highlights the need for comprehensive
      investigations and the advantages of PCR in the diagnosis of patients with
      suspected leishmaniasis in non-endemic regions of the world.

PMID- 16887721
TI  - A loophole in international quarantine procedures disclosed during the SARS
      crisis.
AB  - This study describes a loophole in the international quarantine system during the
      recent Asian severe acute respiratory syndrome (SARS) outbreak. Specifically,
      that of travelers disguising symptoms of respiratory tract infection at
      international airports, in order to board aircraft to return to their home
      countries-notwithstanding the infection risks this involves to others. High
      medical fees for treatment to non-residents in epidemic areas were found to be
      the main cause for this behaviour. This phenomenon revealed a loophole in the
      control mechanisms of international quarantine procedures, letting travelers
      carrying a highly contagious virus slip by undetected and causing possible multi
      country outbreaks of communicable diseases. Clinical evidence collected from
      medical records at medical centers can highlight this oversight.

PMID- 16887722
TI  - Intradermal pre-exposure rabies immunisation in New Zealand.
AB  - BACKGROUND: Rabies is a fatal infection and immunisation is important to consider
      in those travellers going to rabies endemic areas. In those at high risk, a
      course of three immunisations may be given by the intramuscular (IM) or
      intradermal (ID) route, both of which are approved by the World Health
      Organization (WHO) and the Centers for Disease Control (CDC). Little is known in
      the New Zealand context regarding the effectiveness of pre-exposure ID rabies
      immunisation. METHODS: The data was collected prospectively on all travellers
      requiring the immunisation from July 2001 to September 2003 in Auckland. The
      standard WHO rabies immunisation protocol was used with three ID injections of
      0.1 ml, given on days 0, 7, and 21 or 28 with a booster after 12 months. The
      vaccine used was the Pasteur Merieux human diploid cell vaccine (HDCV) or the
      Rabipur Purified chick embryo cell (PCEC) vaccine. Both vaccines are approved by
      the WHO and the CDC, and are interchangeable. Serology was performed
      approximately 2 weeks after completion of the primary immunisation course or
      after a booster, wherever possible. Antibody levels were measured using EIA, and
      levels of >0.5 IU/ml were considered protective. RESULTS: Of the 263 travellers
      assessed in this study, 125 were males and 138 were females. The mean age of the
      cohort was 34.8 years (SD=11.7). There were not found to be any statistically
      significant correlations between age and antibody levels neither was there any
      significant association between gender and antibody levels. In addition to the
      sample group, a further 12 travellers had rabies serology performed but were
      excluded from the study because they had IM vaccines as part of their primary
      course. Whilst rabies serology ranged from 0.2 to 27.9 IU/ml in the study cohort,
      the mean antibody level for the group was 4.7 IU/ml (SD=4.1 IU/ml). The mean
      antibody level for males was 4.3 IU/ml (SD=3.3), and for females, 5.2 IU/ml
      (SD=4.6). Of the 263 travellers, all had some level of detectable antibodies. The
      overall seroconversion rate was 95.1%. CONCLUSIONS: ID rabies immunisation
      appears effective, when given according to the standard WHO protocol, in New
      Zealand. ID rabies immunisation is also more affordable for travellers,
      especially those on a restrictive budget. ID rabies immunisation can continue to
      be recommended, particularly where follow-up serology can be done before travel
      and where there are staff who are experienced in ID immunisation.

PMID- 16887723
TI  - Alveolar echinococcosis in a Thai patient after migration to an endemic area in
      Central Europe.

PMID- 16887724
TI  - Oral cholera vaccine--for whom, when, and why?
AB  - The search for a safe, effective, well tolerated, low cost vaccine against the
      ancient cholera enemy has been ongoing since the 19th century and has been
      revitalized in the past two decades since the advent of recombinant technology.
      Large-scale field trials have readily demonstrated the tolerability and safety of
      oral cholera vaccine in various forms. Variable levels of protection have been
      shown and one challenge has been to demonstrate whether this is a cost effective
      treatment in differing environments including its use in endemic and epidemic
      areas as well as for travelers. A review of recent literature was undertaken to
      assess the effectiveness and uses of currently available oral cholera vaccine.
      While the evidence does not support the creation of formal guidelines, some clear
      recommendations can be made. There is undoubtedly the potential to reduce the
      burden of illness both in endemic and epidemic situations. For travelers, certain
      higher risk groups may benefit from protection against cholera. More
      significantly, the short term cross-protection afforded by whole cell, B subunit
      (WC BS) oral cholera vaccine formulations against enterotoxigenic E. coli,
      (ETEC), the commonest causative agent of traveler's diarrhoea, may prove to be
      the most important raison d'etre.

PMID- 16887725
TI  - The severe acute respiratory syndrome: impact on travel and tourism.
AB  - SARS and travel are intricately interlinked. Travelers belonged to those
      primarily affected in the early stages of the outbreak, travelers became vectors
      of the disease, and finally, travel and tourism themselves became the victims.
      The outbreak of SARS created international anxiety because of its novelty, its
      ease of transmission in certain settings, and the speed of its spread through jet
      travel, combined with extensive media coverage. The psychological impacts of
      SARS, coupled with travel restrictions imposed by various national and
      international authorities, have diminished international travel in 2003, far
      beyond the limitations to truly SARS hit areas. Governments and press, especially
      in non SARS affected areas, have been slow to strike the right balance between
      timely and frequent risk communication and placing risk in the proper context.
      Screening at airport entry points is costly, has a low yield and is not
      sufficient in itself. The low yield in detecting SARS is most likely due to a
      combination of factors, such as travel advisories which resulted in reduced
      travel to and from SARS affected areas, implementation of effective pre-departure
      screening at airports in SARS-hit countries, and a rapid decline in new cases at
      the time when screening was finally introduced. Rather than investing in airport
      screening measures to detect rare infectious diseases, investments should be used
      to strengthen screening and infection control capacities at points of entry into
      the healthcare system. If SARS reoccurs, the subsequent outbreak will be smaller
      and more easily contained if the lessons learnt from the recent epidemic are
      applied. Lessons learnt during the outbreak in relation to international travel
      will be discussed.

PMID- 16887727
TI  - Effects of weight, age, and time on artemether-lumefantrine associated
      ototoxicity and evidence of irreversibility.
AB  - An association between artemether-lumefantrine treatment of uncomplicated
      falciparum malaria and decreases in audiometrically determined hearing thresholds
      has been reported. Questions arising from this report were whether the effect
      described is attributable to drug or disease, the effects of subject weight and
      age on audiometric changes, and whether the changes are reversible. Spearman's
      correlation coefficients were calculated to look for relationships between
      audiometric changes and: (1) the interval spanning artemether-lumefantrine
      exposure and study exit audiogram; (2) subject age; (3) subject weight. The study
      utilised prospectively collected data from an occupational health clinic in
      Mozambique (N = 150). The exposure-exit audiogram interval ranged from 3 to 392
      days (mean 163.8 days, SD 91.91 days). Spearman's correlation coefficients were
      effectively zero for analyses (1) and (2), and too weak to contribute
      significantly to variances for analysis (3). Previous audiometric studies in
      malaria patients and healthy volunteers point away from malaria as causing
      irreversible audiometric changes. The audiometric changes associated with the
      artemether-lumefantrine treatment of malaria appear irreversible. Ototoxicity is
      common to many antimalarials and the elucidation of a common antiparasitic and
      ototoxic pathway will assist in the design of safer new antimalarials.

PMID- 16887726
TI  - Fever in travelers returning from tropical areas: prospective observational study
      of 613 cases hospitalised in Marseilles, France, 1999-2003.
AB  - BACKGROUND: Febrile travelers may pose a diagnostic challenge for Western
      physicians who are frequently involved in the assessment of these patients but
      unfamiliar with tropical diseases. Evaluation of this situation requires an
      understanding of the common etiologies, which are associated with the
      demographics of travelers and the destinations. METHODS: We conducted a 5-year
      prospective observational study on the etiologies of fever in travelers returning
      from the tropics admitted to the infectious and tropical diseases unit of a
      university teaching hospital in Marseilles, France. RESULTS: A total of 613
      patients were enrolled, including 364 migrants (59.4%), 126 travelers (20.6%), 37
      visitors (6%), 24 expatriates (3.9%), and 62 patients (10.1%) who could not be
      classified. Malaria was the most common diagnosis (75.2%), with most cases (62%)
      acquired by migrants from the Comoros archipelago and who had traveled to these
      islands to visit friends and relatives. Agents of food-borne and water-borne
      infections (3.9%) and respiratory tract infections (3.4%) were also frequently
      identified as the cause of fever. Other infections included emerging diseases
      such as gnathostomiasis, hepatitis E infection and rickettsial diseases, as well
      as common infections or exotic diseases. CONCLUSIONS: Although we have identified
      here various causes of imported fever, 8.2% of the fevers remained unexplained.
      An improved approach to diagnosis may allow for the discovery of new diseases in
      travelers in the future.

PMID- 16887728
TI  - Serum procalcitonin in uncomplicated falciparum malaria: a preliminary study.
AB  - BACKGROUND: Procalcitonin (PCT) has been found elevated in complicated forms of
      Plasmodium falciparum malaria. Its usefulness has almost never been assessed in
      uncomplicated falciparum malaria. METHOD: We assessed diagnostic and prognostic
      value of PCT in a prospective series of 25 adults with uncomplicated P.
      falciparum malaria. Patients originated mainly from western Africa and were
      infected during a stay back in their native country (19 semi-immune and 6 non
      immune subjects; 11 had not received any chemoprophylaxis). RESULTS: Parasitaemia
      ranged from 0.01 to 3%. Eighteen patients had their first PCT determined at
      admission or within 24h thereafter (mean +/- SD: 3.0 +/- 4.6 ng/ml; range: 0.1
      19.7). PCT was higher than 0.5 ng/ml in 14 patients (78%), higher than 2 ng/ml in
      7 (39%). PCT correlated with parasitaemia (r = 0.53; p = 0.027), not with C
      reactive protein (CRP). Delay between first symptoms and diagnosis was much
      longer among patients with PCT higher than 2 ng/ml than among those with a lower
      PCT. CONCLUSION: PCT was often elevated in uncomplicated malaria, especially when
      delay between first symptoms and diagnosis was long or parasitaemia was high
      (prognostic marker).

PMID- 16887730
TI  - International travel and sexually transmitted diseases.
AB  - Despite concerted efforts to control sexually transmitted diseases (STDs)
      worldwide, they still remain a major public health problem. Out of the 25
      organisms known to be transmitted sexually, travelers are at greater risk of
      acquiring HIV and other STDs in developing countries in view of the high
      prevalence rates in these countries, particularly after sexual exposure to local
      commercial sex workers (CSWs). Some of the STDs acquired during international
      travel are more likely to be resistant to standard antimicrobial regimens for the
      STDs. HIV, gonorrhoea, syphilis, non-specific urethritis, hepatitis B, hepatitis
      C, and other STDs are a significant risk for travelers who engage in unprotected
      sex, especially with overseas CSWs. It is recognized that barrier contraceptives
      provide considerable protection against STDs, but they are not regarded as 100%
      protective. Sexual abstinence and sexual monogamy with a 'known' partner carry a
      much lower risk than the safest of 'safer sex' practices. However, in the event
      of a sexual exposure to a new partner in the country being visited, prior
      hepatitis B immunization and the consistent and proper use of a latex condom are
      strongly advised, followed by proper medical investigations and physical
      examination on returning home, before sexual activity is resumed.

PMID- 16887729
TI  - Malaria prevention and stand-by emergency treatment among Japanese travelers.
AB  - BACKGROUND: While chemoprophylaxis remains the safest option for most travelers
      to malaria high-risk areas, stand-by emergency treatment (SBET) may also be a
      sensible option especially for travelers to low-risk areas, due to the possible
      adverse effects (AEs) of prophylactic antimalarials. However, studies on the
      suitability of SBET actually implemented by travelers are scarce, especially
      those targeting Japanese travelers. We investigated to what extent malaria
      prevention measures are taken and how effectively SBET is used by Japanese
      travelers to malaria-endemic areas. MATERIALS AND METHODS: A questionnaire study
      was conducted targeting Japanese travelers who visited quarantine stations for
      pre-travel health advice and who had previously visited malaria-endemic areas as
      defined by the World Health Organization (N = 160). RESULTS: The results showed
      that only a minority (13%) of travelers to malaria-endemic areas took
      chemoprophylaxis. Although most (89%) of the SBET users (N = 9) took antimalarial
      drugs when they experienced both fever and chills, characteristic of clinical
      malaria, there were several problems related to SBET. Some (22%) of the subjects
      conducted SBET less than 7 days after entering the area, most (89%) of them did
      so when a medical facility was readily accessible, and many (56%) failed to seek
      medical attention soon after SBET or did not at all. CONCLUSIONS: Japanese
      travelers to malaria-endemic areas seemed less protected with the use of
      chemoprophylaxis. Furthermore, problems related to SBET among Japanese travelers
      were identified. These should be taken into full consideration when educating
      both travelers and travel health professionals to avoid risks of malaria and
      possible AEs of antimalarial drugs.

PMID- 16887731
TI  - Late vaccination against yellow fever of travelers visiting endemic countries.
AB  - BACKGROUND: Guidelines issued by the WHO call for immunization against yellow
      fever (YF) at least 10 days before entering an endemic area. We assessed the
      extent at which travelers complied with these guidelines. METHODS: A two-phase
      study at one travel center in Israel. Phase I-travelers planning to visit YF
      endemic areas (n = 295) were evaluated in regard to the timing of administration
      of YF vaccine before travel. Phase II-the specific causes of arriving late were
      studied prospectively in another group of 132 travelers. RESULTS: Phase I-one
      half of the travelers (n = 148) headed to South America (SA), and 147 to Africa.
      The mean age (+/-SD) of this cohort was 30.9 (+/-14.9) years (range 6-75 years).
      Overall, 64 (21.7%; 95% confidence interval, 17.4-26.8) received the vaccine less
      then 10 days before departure. However, only 10.8% of those heading to SA arrived
      late, as compared to 32.7% of those heading to Africa (p < 0.0001). Phase II-a
      last minute's decision was the commonest reason given for arriving late (43.2%).
      CONCLUSION: One-fifth of travelers fail to comply with the WHO guidelines
      concerning YF vaccination. Travelers and travel agents alike need to be reminded
      of the importance of timely vaccination against YF.

PMID- 16887734
TI  - Running a travel clinic.
AB  - Annually, 1.5 billion passengers travel by air and 700 million travellers cross
      international borders, and around 50% of them can become unwell in some way. In
      today's world travel is important for business people as it is for humanitarian
      groups and immigrants, as it is also for holiday makers. All travellers need to
      be aware of potential health problems and consequences of their travel, and they
      need up to date authoritative advice. Travel health clinics provide this advice
      in a structured, practical and authoritative format. Such a format is discussed,
      and applied with the skills of medical, nursing and management practitioners. The
      four steps for giving travellers the foundation for healthy journeys are all
      explored: to assess pre-health, to analyse itineraries, to select appropriate
      vaccines, and to provide education about the prevention and self-treatment of
      travel-related diseases.

PMID- 16887735
TI  - Risk assessment in travel medicine.
AB  - Risk assessment is an integral part of pre-travel and post- assessment. Risk
      assessment largely determines what health and safety advice and interventions are
      given within the relevant prevailing travel health guidelines. Risk assessment
      needs time and depends on information, including that given by the traveller.
      Risk assessment also needs to be documented. Risk assessment of the traveller
      preferably starts before they enter the consulting room, where travellers may
      complete a pre-travel health questionnaire. Armed with this information, risk
      assessment may be assisted by access to computerised travel health databases and
      the published literature. Experience of travel to the destination may also assist
      in risk assessment and the tour operator, overseas employer or agency, the
      traveller or even the travel health advisers themselves may provide this
      information.

PMID- 16887736
TI  - Accidents and repatriation.
AB  - Accidents and injury contribute greatly to the morbidity and mortality of
      travellers worldwide, with road traffic accidents being a major contributer.
      Those travelers with serious illness and injury may need specialised medical
      evacuation services, which may involve an air ambulance and a specialised medical
      team. Such aeromedical repatriations require considerable organisation and
      liaison between the sending and receiving medical services and other interested
      parties. However, the majority of travellers requiring emergency assistance are
      stable patients requiring referral for medical or dental attention or special
      requirements for carriage on scheduled aircraft.

PMID- 16887737
TI  - Travelling to Africa: health risks reviewed.
AB  - Africa's varied ecology presents a wide range of travel health threats:
      infections; accidents; envenomations; an uncertain drug supply; problematic
      access to competent medical care outside South Africa. Important vaccine
      preventable diseases include yellow fever, meningococcal disease, typhoid, polio,
      rabies, and hepatitis A and B; routine vaccinations should be up to date. Much,
      but not all, of sub-Saharan Africa is malarious with chloroquine resistant
      falciparum dominating; chemoprophylaxis and personal protection measures will
      often be indicated. Other threats are less obvious, e.g. helminth and protozoal
      infections. The immunocompromised and other high-risk groups may require special
      attention. Risk mitigation strategies may include education, vaccination,
      chemoprophylaxis, personal protection measures, provision of treatment and
      equipment packs, behaviour modification, and evacuation insurance.

PMID- 16887738
TI  - Malaria.
AB  - Malaria is increasing worldwide due to the emergence and spread of drug resistant
      strains. This poses major health and economic problems for the population living
      in endemic areas and increases the risk of infections in travelers. The diagnosis
      of malaria relies on a biological proof of infection by microscopy or with a
      rapid test. The treatment must be initiated without delay preferably with an
      artemisinin containing regimen. Uncomplicated malaria can be treated with oral
      drugs while severe infections will be hospitalized and treated with injectables.
      Special attention will be given to the most susceptible groups: children and
      pregnant women.

PMID- 16887739
TI  - HIV and travel.
AB  - There is a high demand for travel among HIV-positive individual. This demand
      arises partly from those who have benefited from advances in antiretroviral
      therapy as well as those with disease progression. The key to a successful and
      uneventful holiday lies in careful pre-trip planning, yet many patients fail to
      obtain advice before travelling. Travel advice for HIV patients is becoming
      increasingly specialized. In addition to advice on common travel-related
      infectious diseases, HIV-positive travellers are strongly advised to carry
      information with them and they need specific advice regarding country entry
      restrictions, HIV inclusive travel insurance, safety of travel vaccinations and
      highly active antiretroviral therapy-related issues. A wide range of relevant
      issues for the HIV-positive traveller are discussed in this review and useful
      websites can be found at the end.

PMID- 16887740
TI  - Sexually transmitted infections and HIV among travellers: a review.
AB  - Sexually transmitted infections are often acquired during travel. Infections are
      most often seen in young adults, travelling without a regular partner and among
      those who have higher numbers of partners while at home. Alcohol and recreational
      drug use may increase risk. The risks are highest from having unprotected sex
      with local partners in developing countries where the prevalence of infection can
      be many times higher than at home. The risks of acquiring HIV are highest in
      Africa, followed by South Asia. Special precautions are required by those going
      to work in health-care settings in high HIV prevalence countries. Travellers may
      benefit from advice about safer sex, condom use, emergency contraception and
      vaccination against hepatitis B. In special circumstances a starter pack for HIV
      post-exposure prophylaxis should be considered. Following return travellers
      should consider attending specialist services for a screen for sexually
      transmitted infections and HIV if they are concerned about exposure whilst
      travelling. A number of reports suggest that travel clinics need to pay more
      attention to the sexual health of travellers.

PMID- 16887741
TI  - The pregnant traveller.
AB  - Counselling pregnant women seeking advice about travel should begin with a frank,
      in-depth discussion about their contemplated trip. While most travel during
      pregnancy is relatively safe, some women should be urged not to go on their
      planned trip, or to change their itineraries. But some women are not receptive to
      such advice. Much of today's popular culture preaches that pregnancy is a normal
      phase of life, not a health issue, and that restrictions placed on women during
      pregnancy by the medical profession are largely unnecessary. The women must truly
      and totally understand potential risks and realise that medical science does not
      have all the answers, especially as far as risks to the foetus are concerned. The
      women should be aware that travel may remove them from access to medical care,
      require immunisations and prophylactic medications, involve long hours sitting in
      aircraft, necessitate dietary restrictions at the destination, and expose them to
      extremes of climate, to mention just a few.

PMID- 16887742
TI  - Family travel: an overview.
AB  - Paediatric travel medicine involves the education of parents about the numerous
      health and safety issues related to traveling with infants and young children-
      whether overseas or a weekend at a local lake. It includes providing children
      with vaccines and medications, giving telephone advice to parents while they are
      traveling, and treating children should they come home ill. Practitioners must be
      knowledgeable about such varied topics like avoiding diarrhoea, infant safety
      seats for air travel, altitude sickness, sun exposure, waterfront safety, insect
      protection, dealing with hot and cold environments, and at what age it is safe to
      begin scuba diving, to name just a very few. Practitioners must also know when
      adult recommendations can--and cannot--be adapted for children; that vaccine
      doses, needle size, and injection site may vary with the size of the child; and
      the answers to hundreds of everyday questions such as how to administer an
      essential but bitter tasting medication to an uncooperative child--and what to do
      when the child refuses to take the medication or vomits it.

PMID- 16887743
TI  - The elderly travellers.
AB  - As the population increases, older people have the opportunity to travel for
      longer periods and to destinations that are quite different from what they are
      used to. Older people do indeed have more ongoing medical issues and some
      limitations due to the aging process. Most of the time these chronic conditions
      are not a contraindication to travel. Preparing for travel frequently involves
      starting an exercise program, updating routine immunizations such as tetanus,
      pneumonia, and influenza as well as getting destination specific immunizations
      such as hepatitis, yellow fever and typhoid. Medications should be reviewed as
      they relate to altitude, climate and concurrent travel medications including
      malaria prophylaxis. There are many organizations and foundations that deal with
      travel and specific medical problems such as diabetes, asthma, dialysis and for
      those with spinal cord injuries. The traveler would be wise to seek the advice of
      specialists related to their specific medical condition as well as a travel
      medical physician. One should also be sure that their medical insurance would
      cover them in a foreign country.

PMID- 16887744
TI  - Altitude medicine and physiology including heat and cold: a review.
AB  - With increasing numbers of people travelling to high altitude destinations for
      recreation or work, there is a need for practitioners of Travel Medicine to be
      familiar with altitude illnesses and the physiology of altitude. In mountainous
      areas travellers may also be exposed to problems of heat and cold. This article
      reviews these topics and gives practical advice on the management of the clinical
      problems involved, together with a discussion of underlying mechanisms, as far as
      they are understood at present.

PMID- 16887745
TI  - Diving medicine.
AB  - Recreational diving developed in the late 1940s when self-contained underwater
      breathing apparatus (SCUBA) first became available for civilian use. At the same
      time the development of the commercial airliner, in particular the jet airliner,
      made possible the concept of international travel for pleasure as opposed to
      business. Over the past 50 years the number of international tourists has
      increased by over 2500% from a mere 25 million in 1950 to over 700 million in
      2002 (Treadwell TL. Trends in travel. In: Zuckerman JN, editor. Principles and
      practice of travel medicine, 2001; p. 2-6). The popularity of recreational diving
      has also increased over the same period from an activity experienced by a small
      number of individuals in the early 1950s to an activity today enjoyed by many
      millions. The combination of increased international travel and the means by
      which to enter and explore the underwater world has led to diving becoming
      increasingly popular as a tourist activity.

PMID- 16887746
TI  - The circadian regulation of Presenilin-2 gene expression.
AB  - Circadian rhythms are generated by a molecular clock composed of clock genes and
      their protein products. Other genes are regulated in a rhythmic way by this
      molecular clockwork, but are not themselves constituents of the clock. This study
      shows that one of these clock-controlled genes encodes the signalling protein
      Presenilin-2. Indeed, evidence is presented that the promoter of the mouse
      Presenilin-2 gene is bound and activated by CLOCK and BMAL1, transcription
      factors of the mammalian circadian clock. Quantification of Presenilin-2 RNA
      shows that its expression is non-rhythmic in many peripheral tissues (heart,
      muscle, kidney, spleen, and thymus). Note, though, that careful analysis of the
      liver data shows that Presenilin-2 RNA exists in distinct isoforms in this
      tissue, and that rhythmicity is restricted to only a subset of these RNA
      isoforms. These data indicate a unique mode of regulation of Presenilin-2
      transcripts, the circadian control of which appears to happen at the
      transcriptional and post-transcriptional levels.

PMID- 16887747
TI  - Day-night differences in membrane-bound pyroglutamyl-2-naphthylamide-hydrolyzing
      activity in rat hypothalamus, pituitary, and retina.
AB  - Membrane-bound pyroglutamyl-2-naphthylamide-hydrolyzing enzyme activity was
      analyzed fluorometrically in the anterior hypothalamus, pituitary, and retina of
      adult male rats to investigate day-night differences. Six groups (n=6 per group)
      were assessed--three during the light span and three during the dark span--under
      a standard 12 h-12 h light-dark cycle (light on from 07:00 to 19:00 h) and
      controlled temperature environment, with food and water available ad libitum. In
      the hypothalamus, enzyme activity levels were higher for time points of the dark
      than the light period. In contrast, the pituitary and retina exhibited the
      highest levels at the time points of the light period. The pituitary and retina
      also exhibited significant differences between the clock-hour means of the light
      period. Day-night differences in membrane-bound pyroglutamyl-2-naphthylamide
      hydrolyzing activity may reflect differences in its susceptible endogenous
      substrates.

PMID- 16887748
TI  - Comparative study of the activity/rest rhythms in young and old ringdove
      (Streptopelia risoria): correlation with serum levels of melatonin and serotonin.
AB  - Aging is characterized by changes in the circadian rhythms of melatonin,
      serotonin, and sleep/wakefulness, alterations that affect sleep quality. The
      authors studied the circadian rhythms of serotonin and melatonin in young and old
      ringdoves (Streptopelia risoria) (2-3 and 10-12 yrs old, respectively), animals
      that are characterized by being monophasic and active by day, like humans. The
      aim was to correlate the indole rhythms with the animals' activity/rest periods.
      The animals were kept under a 12:12 h light/dark cycle, fed ad libitum, and
      housed in separate cages equipped for activity recording. Activity pulses were
      recorded with one actometer per animal (two perpendicular infrared transmitters)
      and were logged every 15 min by a computer program (DAS 16) throughout the
      experiment. Melatonin was measured by radioimmunoassay and serotonin by ELISA at
      intervals of 3 h (from 09:00 to 18:00 h) and 1 h (from 21:00 to 06:00 h),
      respectively. The results showed a reduction in nocturnal vs. diurnal activity of
      89% and 61% in the young and old animals, respectively, with 100% considered to
      be the diurnal activity of each group. The amplitude of a cosine function fit to
      the melatonin concentrations of the old animals was half that of the young birds.
      The acrophase and nadir were at 02:00 and 14:00 h in the young and 01:00 and
      13:00 h in the old animals, respectively. The amplitude of the corresponding
      cosine function fit to the serotonin concentrations in the old birds was one
      third that of the young animals. The acrophase and nadir were at 15:00 and 03:00
      h in the young and 16:00 and 04:00 h in the old animals, respectively. For both
      melatonin and serotonin, the concentrations in the young animals were
      significantly higher than in the old at most of the measurement times. There was
      a clear negative correlation between the circadian rhythms of activity and the
      serum melatonin levels in both young and old animals. The equivalent correlation
      for serotonin was positive, and stronger in the case of the young animals. The
      results suggest a possible relationship between the observed decline in the
      amplitude of the old animals' melatonin and serotonin rhythms and the lower
      percentage reduction in their nocturnal relative to diurnal activity pulses
      compared to the young animals. In conclusion, the circadian rhythms of melatonin
      and serotonin undergo alterations with age that could be involved in the changes
      in age-associated sleep.

PMID- 16887749
TI  - Circadian rhythms in heart rate, motility, and body temperature of wild-type C57
      and eNOS knock-out mice under light-dark, free-run, and after time zone
      transition.
AB  - The nitric oxide (NO) system is involved in the regulation of the cardiovascular
      system in controlling central and peripheral vascular tone and cardiac functions.
      It was the aim of this study to investigate in wild-type C57BL/6 and endothelial
      nitric oxide synthase (eNOS) knock-out mice (eNOS-/-) the contribution of NO on
      the circadian rhythms in heart rate (HR), motility (motor activity [MA]), and
      body temperature (BT) under various environmental conditions. Experiments were
      performed in 12:12 h of a light:dark cycle (LD), under free-run in total darkness
      (DD), and after a phase delay shift of the LD cycle by -6 h (i.e., under
      simulation of a westward time zone transition). All parameters were monitored by
      radiotelemetry in freely moving mice. In LD, no significant differences in the
      rhythms of HR and MA were observed between the two strains of mice. BT, however,
      was significantly lower during the light phase in eNOS-/- mice, resulting in a
      significantly greater amplitude. The period of the free-running rhythm in DD was
      slightly shorter for all variables, though not significant. In general,
      rhythmicity was greater in eNOS-/- than in C57 mice both in LD and DD. After a
      delay shift of the LD cycle, HR and BT were resynchronized to the new LD schedule
      within 5-6 days, and resynchronization of MA occurred within 2-3 days. The
      results in telemetrically instrumented mice show that complete knock-out of the
      endothelial NO system--though expressed in the suprachiasmatic nuclei and in
      peripheral tissues--did not affect the circadian organization of heart rate and
      motility. The circadian regulation of the body temperature was slightly affected
      in eNOS-/- mice.

PMID- 16887750
TI  - Gender dependency of circadian blood pressure and heart rate profiles in
      spontaneously hypertensive rats: effects of beta-blockers.
AB  - This study investigated (i) blood pressure (BP), heart rate (HR), and their
      relation to urinary NOx and eNOS protein expression in male and female
      spontaneously hypertensive rats (SHR), as well as (ii) gender-dependent
      cardiovascular effects of nebivolol (NEB) in comparison to metoprolol (MET) in
      SHR. BP and HR were measured telemetrically after a single intraperitoneal
      application of NEB or MET at 07.00 and 19.00 h in male rats and at 19.00 h in
      proestrus female rats. The two beta-blockers varied in time of decreasing BP and
      HR and also in duration. In males, MET decreased BP and HR for few hours
      exclusively when applied at the onset of the activity phase (i.e., at 19.00 h),
      while after its application at 07.00 h, BP and HR were unchanged. In females, MET
      also caused a short-lasting BP and HR reduction, with the effect being more
      pronounced than in males. In males, NEB at either dosing time decreased HR and BP
      to a greater extent than did MET. This effect was evident both during the
      activity and rest periods and persisted for at least five days. In females, NEB
      provoked a similar, but more pronounced, effect on BP and HR in comparison to
      males. These findings demonstrate that significant gender-dependent differences
      in the circadian profile of BP and HR exist. BP and urinary NOx as well as eNOS
      expression are inversely correlated, and the cardiovascular effects of NEB and
      MET vary, depending on the time of application as well as gender.

PMID- 16887751
TI  - Age-related differences in the lifestyle regularity of seniors experiencing
      bereavement, care-giving, insomnia, and advancement into old-old age.
AB  - Compared to younger adults, seniors (> or = 60 yrs) often adopt a highly regular
      lifestyle, perhaps as an adaptive response to age-related changes in their sleep
      and circadian rhythms. At baseline, diary measures of lifestyle regularity (SRM
      5) were obtained from 104 seniors of three separate groups. Thirty-three subjects
      were challenged by spousal bereavement or the need to care for a spouse at home
      with dementia (Challenged); 33 were suffering from formally diagnosed (DSM-IV)
      insomnia (Insomnia); and 38 were healthy, well-functioning older seniors in the
      second half of their eighth decade of life or later (Healthy Older). The
      objective of this study was to determine whether lifestyle regularity increased
      as a function of age within each of these three senior groups. Overall, age was
      significantly correlated with SRM-5 (r=0.41, p<0.001), with the SRM score
      increasing by 0.67 units/decade. The same was true for the Challenged and
      Insomnia groups, which also showed a significant correlation between SRM and age
      (Challenged: r=0.48, p<0.01; Insomnia: r=0.36, p<0.05), though with a slightly
      faster rate of SRM increase in the Challenged (0.95 units/decade) than Insomnia
      (0.55 units/decade) group. Perhaps there was no correlation between age and SRM
      (r=0.07, n.s.) in the Healthy Older group due to the small age range, although
      this group did have a higher overall SRM score than the other two groups
      (p<0.01). The study thus confirmed that the previously observed increase in
      lifestyle regularity over the adult lifespan persists into later life. This may
      represent an adaptive behavioral response that might be used in future
      therapeutic approaches.

PMID- 16887752
TI  - Aircrew fatigue in trans-Atlantic morning and evening flights.
AB  - The aim of the investigation was to compare sleepiness and sleep on westward
      morning and evening flights. Seven morning-crew pilots and seven evening-crew
      pilots participated. Data were collected before, during, and after outward-bound
      (westward) and homeward-bound (eastward) flights across six time zones. A
      sleep/wake diary (with repeated sleepiness and performance ratings) and wrist
      actigraphy were used for data collection. Maximum sleep was obtained after return
      and minimum sleep before the outward-bound flights. Actigraphy measures and sleep
      efficiency over the course of the study showed no significant differences between
      the morning and evening crews. There was a trend for a significant effect of
      morning vs. evening flight for time with heavy eyelids, with the homeward-bound
      flight showing more time with heavy eyelids. There were no significant
      differences between morning and evening crews with regard to napping during the
      flight. The duration of wakefulness was longer for the evening flight crew. There
      were significant interactions for Karolinska sleepiness scale (KSS) self-ratings
      on both the outward-bound and homeward-bound flights, and KSS was elevated during
      a considerable portion of the evening flights. Rated performance showed a
      significant time effect, but there was no difference in self-ratings between
      morning and evening crews. Evening flights involve higher levels of sleepiness
      than morning flights, presumably because of the close proximity in time to the
      circadian trough of alertness.

PMID- 16887754
TI  - Effect of pedal rate on diurnal variations in cardiorespiratory variables.
AB  - Recently, it was observed that the freely chosen pedal rate of elite cyclists was
      significantly lower at 06:00 than at 18:00 h, and that ankle kinematics during
      cycling exhibits diurnal variation. The modification of the pedaling technique
      and pedal rate observed throughout the day could be brought about to limit the
      effect of diurnal variation on physiological variables. Imposing a pedal rate
      should limit the subject's possibility of adaptation and clarify the influence of
      time of day on physiological variables. The purpose of this study was to
      determine whether diurnal variation in cardiorespiratory variables depends on
      pedal rate. Ten male cyclists performed a submaximal 15 min exercise on a cycle
      ergometer (50% Wmax). Five test sessions were performed at 06:00, 10:00, 14:00,
      18:00, and 22:00 h. The exercise bout was divided into three equivalent 5 min
      periods during which different pedal rates were imposed (70 rev x min(-1), 90 rev
      x min(-1) and 120 rev x min(-1)). No significant diurnal variation was observed
      in heart rate and oxygen consumption, whatever the pedal rate. A significant
      diurnal variation was observed in minute ventilation (p=0.01). In addition, the
      amplitude of the diurnal variation in minute ventilation depended on pedal rate:
      the higher the pedal rate, the greater the amplitude of its diurnal variation
      (p=0.03). The increase of minute ventilation throughout the day is mainly due to
      variation in breath frequency (p=0.01)--the diurnal variation of tidal volume
      (all pedal rate conditions taken together) being non-significant--but the effect
      of pedal rate x time of day interaction on minute ventilation specific to the
      higher pedal rate conditions (p=0.03) can only be explained by the increase of
      tidal volume throughout the day. Even though an influence of pedal rate on
      diurnal rhythms in overall physiological variables was not also evidenced, high
      pedal rate should have been imposed when diurnal variations of physiological
      variables in cycling were studied.

PMID- 16887753
TI  - A compromise phase position for permanent night shift workers: circadian phase
      after two night shifts with scheduled sleep and light/dark exposure.
AB  - Night shift work is associated with a myriad of health and safety risks. Phase
      shifting the circadian clock such that it is more aligned with night work and day
      sleep is one way to attenuate these risks. However, workers will not be satisfied
      with complete adaptation to night work if it leaves them misaligned during days
      off. Therefore, the goal of this set of studies is to produce a compromise phase
      position in which individuals working night shifts delay their circadian clocks
      to a position that is more compatible with nighttime work and daytime sleep yet
      is not incompatible with late nighttime sleep on days off. This is the first in
      the set of studies describing the magnitude of circadian phase delays that occurs
      on progressively later days within a series of night shifts interspersed with
      days off. The series will be ended on various days in order to take a "snapshot"
      of circadian phase. In this set of studies, subjects sleep from 23:00 to 7:00 h
      for three weeks. Following this baseline period, there is a series of night
      shifts (23:00 to 07:00 h) and days off. Experimental subjects receive five 15 min
      intermittent bright light pulses (approximately 3500 lux; approximately 1100
      microW/cm2) once per hour during the night shifts, wear sunglasses that attenuate
      all visible wavelengths--especially short wavelengths ("blue-blockers")--while
      traveling home after the shifts, and sleep in the dark (08:30-15:30 h) after each
      night shift. Control subjects remain in typical dim room light (<50 lux)
      throughout the night shift, wear sunglasses that do not attenuate as much light,
      and sleep whenever they want after the night shifts. Circadian phase is
      determined from the circadian rhythm of melatonin collected during a dim light
      phase assessment at the beginning and end of each study. The sleepiest time of
      day, approximated by the body temperature minimum (Tmin), is estimated by adding
      7 h to the dim light melatonin onset. In this first study, circadian phase was
      measured after two night shifts and day sleep periods. The Tmin of the
      experimental subjects (n=11) was 04:24+/-0.8 h (mean+/-SD) at baseline and 7:36+/
      1.4 h after the night shifts. Thus, after two night shifts, the Tmin had not yet
      delayed into the daytime sleep period, which began at 08:30 h. The Tmin of the
      control subjects (n=12) was 04:00+/-1.2 h at baseline and drifted to 4:36+/-1.4 h
      after the night shifts. Thus, two night shifts with a practical pattern of
      intermittent bright light, the wearing of sunglasses on the way home from night
      shifts, and a regular sleep period early in the daytime, phase delayed the
      circadian clock toward the desired compromise phase position for permanent night
      shift workers. Additional night shifts with bright light pulses and daytime sleep
      in the dark are expected to displace the sleepiest time of day into the daytime
      sleep period, improving both nighttime alertness and daytime sleep but not
      precluding adequate sleep on days off.

PMID- 16887758
TI  - Neurosciences and the Third Reich introduction.

PMID- 16887755
TI  - Increased REM sleep associated with melatonin deficiency after pinealectomy: a
      case study.
AB  - The objectives of the investigation were to assess hypersomnia, which
      progressively appeared in a young patient after a pinealectomy, chemotherapy, and
      radiotherapy for a typical germinoma, as well as the potential benefit of
      melatonin administration in the absence of its endogenous secretion. 24 h
      ambulatory polysomnography and the Multiple Sleep Latency Test (MSLT) were
      performed; in addition, daily plasma melatonin, cortisol, growth hormone,
      prolactin, and rectal temperature profiles were determined before and during
      melatonin treatment (one 2 mg capsule given nightly at 21:00 h for 4 weeks). MSLT
      showed abnormal sleep latency and two REM sleep onsets. Nighttime total sleep
      duration was lengthened, mainly as a consequence of an increased REM sleep
      duration. These parameters were slightly modified by melatonin replacement.
      Plasma melatonin levels, which were constantly nil in the basal condition, were
      increased to supraphysiological values with melatonin treatment. The plasma
      cortisol profile showed nycthemeral variation within the normal range, and the
      growth hormone profile showed supplementary diurnal peaks. Melatonin treatment
      did not modify the secretion of either hormone. The plasma prolactin profile did
      not display a physiological nocturnal increase in the basal condition; however,
      it did during melatonin treatment, with the rise coinciding with the nocturnal
      peak of melatonin concentration. A 24 h temperature rhythm of normal amplitude
      was persistent, though the mean level was decreased and the rhythm was dampened
      during melatonin treatment. The role of radiotherapy on the studied parameters
      cannot be excluded; the findings of this case study suggest that the observed
      hypersomnia is not the result of melatonin deficiency alone. Overall, melatonin
      treatment was well tolerated, but the benefit on the sleep abnormality,
      especially on daytime REM sleep, was minor, requiring the re-introduction of
      modafinil treatment.

PMID- 16887759
TI  - Neuropathological research at the "Deutsche Forschungsanstalt fuer Psychiatrie"
      (German Institute for Psychiatric Research) in Munich (Kaiser-Wilhelm-Institute).
      Scientific utilization of children's organs from the "Kinderfachabteilungen"
      (Children's Special Departments) at Bavarian State Hospitals.
AB  - During National Socialism, the politically motivated interest in psychiatric
      genetic research lead to the founding of research departments specialized in
      pathological-anatomical brain research, the two Kaiser Wilhelm-Institutes (KWI)
      in Berlin and Munich. The latter was indirectly provided with brain material by
      Bavarian State Hospitals, to three of which "Kinderfachabteilungen" (Special
      Pediatric Units) were affiliated. As children became victims of the
      systematically conducted child "euthanasia" in these Special Pediatric Units,
      this paper will address the question whether and to which extent the organs from
      victims of child "euthanasia" were used for (neuro-) pathological research at the
      KWI in Munich. By means of case studies and medical histories (with focus on the
      situation in Kaufbeuren-Irsee), I will argue that pediatric departments on a
      regular base delivered slide preparations, that the child "euthanasia" conduced
      in these departments systematically contributed to neuropathological research and
      that slide preparations from victims of child "euthanasia" were used in
      scientific publications after 1945.

PMID- 16887760
TI  - Neurosciences and research on chemical weapons of mass destruction in Nazi
      Germany.
AB  - As a side-product of industrial research, new chemical nerve agents (Tabun,
      Sarin, Soman) superior to those available to the Allied Forces were discovered in
      Nazi Germany. These agents were never used by Germany, even though they were
      produced at a large scale. This article explores the toxicological and
      physiological research into the mechanisms of action of these novel nerve agents,
      and the emergence of military research objectives in neurophysiological and
      neurotoxicological research. Recently declassified Allied military intelligence
      files document secret nerve agent research, leading to intensified research on
      anticholinesterase agents in the peripheral and the central nervous system. The
      article discusses the involvement of IG Farben scientists, educational, medical
      and military institutions, and of Nobel Prize laureate Richard Kuhn, director of
      the Kaiser Wilhelm Institute for Medical Research.

PMID- 16887761
TI  - Phases in the postwar German reception of the "Euthanasia Program" (1939-1945)
      involving the killing of the mentally disabled and its exploitation by
      neuroscientists.
AB  - The killing of disabled patients with mental diseases during 1939-1945 is
      regarded as the precursor to the Holocaust. Although known at least since the
      Nuremberg Doctors Trial (1946-1947), the reception accorded these crimes against
      humanity varied (and evolved through time) depending on the parties: the old
      establishment, the younger generation, the different political interests, and the
      jurists, the theologians, the historians, the medical authorities. I attempt to
      distinguish five phases in the debate in light of the political background
      between 1945 until the present.

PMID- 16887762
TI  - A possible account of synaesthesia dating from the seventeenth century.
AB  - An account of a blind man able to detect colors by touch, dating from the mid
      seventeenth century, is presented. The details come to us through the physician
      John Finch, the scientist Robert Boyle, and the author Jonathan Swift. The
      details in the account suggest the possibility that this may be an early report
      of colored-touch synaesthesia.

PMID- 16887763
TI  - Seventeenth century concepts of "apoplexy" as reflected in Bonet's
      "Sepulchretum".
AB  - The term "apoplexy," which has been in use since antiquity, referred to a
      catastrophic illness with an abrupt loss of consciousness and a frequently fatal
      outcome. During the sixteenth and seventeenth centuries scholastic approaches
      that relied on authorities were merging with an observational approach to
      medicine and Galen's speculation that apoplexy was due to an accumulation of
      phlegm or black bile in the cerebral ventricles began to be seriously challenged.
      The most extensive collection of case reports with autopsies published in the
      seventeenth century was Theophile Bonet's Sepulchretum sive Anatomia Practica.
      Section 2 of Book I of the Sepulchretum contains 70 case reports of patients that
      died with the diagnosis of apoplexy. The scholia in this section provide an idea
      for the modern reader of the notions physicians had of apoplexy in the
      seventeenth century. The Sepulchretum was an important book for physicians of the
      late seventeenth and eighteenth centuries. It played an important role in the
      development of modern medicine and it was an important foundation for Morgagni's
      De Sedibus et Causis Morborum. This essay reviews the pathological findings
      reported in victims of apoplexy and examines the views concerning the
      symptomatology, pathogenesis, etiology, and treatment of this condition that were
      prevalent at that time.

PMID- 16887764
TI  - Nicolas Saucerotte: Acromegaly before Pierre Marie.

PMID- 16887765
TI  - NEUROwords "Munchausen Syndrome by Proxy": Karl Friedrich Hieronymus, Baron von
      Munchhausen, hasn't got anything to do with it.

PMID- 16887774
TI  - Divergent thinking in Alzheimer's and frontotemporal dementia.
AB  - Twenty-three patients with mild dementia of the Alzheimer's type (DAT) or
      frontotemporal type (DFT) and age- and education-matched control subjects were
      administered tests of complex fluency involving divergent thinking and tests of
      letter, category, and figural fluency. The tests of complex fluency discriminated
      the dementia patients from control subjects more strongly than did the other
      fluency tests. The results suggest that divergent thinking as assessed by complex
      fluency tests is a cognitive domain that is impaired early in the course of
      dementia. The sensitivity of complex fluency tests compared to that of letter,
      category, and figural fluency tests may be related to greater demands for
      conceptualization in relating stimulus attributes to function and greater demands
      for flexible thinking during self-directed search processes.

PMID- 16887775
TI  - Verified hormone therapy improves episodic memory performance in healthy
      postmenopausal women.
AB  - Studies of hormone therapy (HT) and cognition have yielded conflicting results.
      The aim of this observational study was to examine the effect of estradiol, via
      serum verified HT (estradiol, estriol, progesterone) and endogenous estradiol, on
      108 healthy postmenopausal women's cognitive performance. The results
      demonstrated that the 43 HT-users performed at a significantly higher level than
      non-users on episodic memory tasks and on a verbal fluency task, whereas HT-users
      and non-users did not differ on tasks assessing semantic memory and spatial
      visualization. In addition, there was a positive relationship between serum
      estradiol level and episodic memory performance, indicating that postmenopausal
      HT is associated with enhanced episodic memory and verbal fluency, independent of
      age and education. These observational results suggest that HT use may be
      sufficient to exert small, yet positive effects on female sensitive cognitive
      tasks. Hormone therapy compliance and formulation is discussed as confounding
      factors in previous research.

PMID- 16887776
TI  - Repetition priming across the adult lifespan--the long and short of it.
AB  - Previous reports suggest that repetition priming (i.e., enhanced processing of a
      stimulus after experience with that stimulus) is long lasting and impervious to
      the effects of age, in contrast to the pattern found with explicit memory.
      However, the nature of repetition priming in aged individuals remains unclear, as
      conflicting findings have also been reported. We used a longitudinal design to
      examine how repetition priming is affected by multiple stimulus repetitions
      (three presentations) and different delay intervals (no delay, 1 day, 1 week, and
      1 month) in young adults, as well as in two groups of aging adults (young-elderly
      and old-elderly). Our findings extend previous reports that priming is long
      lasting, even when 1 month intervenes between the initial experience with an item
      and the subsequent priming test of that item (Cave, 1997), and is relatively
      impervious to the effects of age (Mitchell, et al., 1990). In addition, a more
      detailed characterization of priming and the effects of aging was revealed.
      Although priming is long lasting, remaining significant even at the month delay
      for all groups, it did decline over time and the rate of that decline differed
      with age. Both young-elderly and old-elderly groups showed a marked drop-off at 1
      day, whereas young adults did not show a decline until 1 week. All groups
      benefited from multiple repetitions; however, this benefit disappeared at the
      month delay (in contrast to recognition memory, where the benefit remained
      significant). These findings support the assertion that repetition priming and
      explicit memory reflect the operation of distinct systems, and that these systems
      may undergo different rates of change in aging.

PMID- 16887777
TI  - The relation of white matter hyperintensities to cognitive performance in the
      normal old: education matters.
AB  - This study examined whether the severity of cerebral white matter abnormalities
      (evident on MR images as white matter hyperintensities (WMH)) was related to the
      cognitive performance of 141 high-functioning older adults. The elderly showed
      the typical age decrement on measures of processing speed, working memory, and
      inhibition; however WMH severity was significantly related only to processing
      speed. The strength of this relationship was, however, influenced by the
      educational level of the participants, such that processing speed was more
      associated with WMH severity in less-educated than in well-educated participants.
      This is consistent with recent concepts of cognitive reserve, but does raise a
      question as to the underlying source of the cognitive decrement found in the sort
      of well-educated elders typically used in cognitive-aging studies.

PMID- 16887778
TI  - Interference resolution in the elderly: evidence suggestive of differences in
      strategy on measures of prepotent inhibition and dual task processing.
AB  - The ability to effectively resolve interference was investigated in young and
      elderly participants using a test of inhibition and a dual task measure. The
      tasks stressed the ability to suppress prepotent responding, and balance primary
      and secondary task demands, respectively. Successful performance on both measures
      hinged on the ability to minimize the distraction generated between competing
      aspects of each task. Increasing demands resulted in performance decrements
      despite titration for individual differences in span size and generalized
      slowing. These were more pronounced on the hardest condition of each task,
      especially in older participants. Furthermore, the nature of the decrements
      suggested the use of different strategies between groups. It is argued that a
      fundamental source of the age-associated variability in cognition is due to
      compromised ability to effectively resolve interference, and cannot be
      sufficiently explained by memory span differences or generalized slowing.

PMID- 16887779
TI  - Age-related differences in working memory and force control under dual-task
      conditions.
AB  - The aim of this study was to investigate the relationship between force control
      and cognitive performance under dual-task conditions in younger (18-22 years) and
      older adults (65-77 years). Cognitive (n-back test) and motor performance (force
      tracking) was measured independently and simultaneously. Results indicated
      overall age-related differences for the n-back and the force-tracking task. Age
      related differences increased during dual-task conditions. While younger adults
      exhibited no decrease in cognitive or motor performance during dual-task
      conditions, older adults showed a decrease in motor and cognitive performance.
      Additionally, when older adults made an error in the cognitive task they tended
      to show greater variability in the force-tracking task. These results suggest
      that cognitive motor deficits are responsible for older adults' performance
      decrements under dual-task conditions.

PMID- 16887780
TI  - Practice effects on motor control in healthy seniors and patients with mild
      cognitive impairment and Alzheimer's disease.
AB  - This research was designed to test the hypothesis that motor practice can enhance
      the capabilities of motor control in healthy controls (NC) and patients with a
      diagnosis of probable Alzheimer's disease (AD) and mild cognitive impairment
      (MCI), and consequently results in better motor performance. Approximately half
      of the subjects in the NC (n = 31), AD (n = 28), and MCI (n = 29) either received
      or did not receive practice on a task of fast and accurate arm movement with a
      digitizer. Changes in movement time (MT), movement smoothness (jerk), and
      percentage of primary submovement (PPS) were recorded and compared among the
      three groups across six blocks of trials (baseline and five training sessions).
      For all subjects, practice improved motor functions as reflected by faster and
      smoother motor execution, as well as a greater proportion of programming control.
      Compared to unaffected matched controls, AD and MCI subjects exhibited a greater
      reduction in movement jerk due to practice. Movement time and PPS data revealed
      that motor practice appeared to reduce the use of "on-line" correction adopted by
      the AD or MCI patients while performing the aiming movements. Evidently, their
      arm movements were quicker, smoother, and temporally more consistent than their
      untrained peers. The findings of this study shed light on how MCI and AD may
      affect motor control mechanisms, and suggest possible therapeutic interventions
      aimed at improving motor functioning in these impaired individuals.

PMID- 16887781
TI  - The effect of age on rule-based category learning.
AB  - An explicit, rule-based, category-learning task with abstract visual stimuli was
      administered to 50 healthy older adults and 48 younger adults. Accuracy and
      reaction time (RT) were examined for the effects of age, perceptual abilities,
      rule memory, rule complexity, stimulus novelty, and response competition. Older
      adults performed at equivalent levels to younger adults when applying a simple
      rule, but showed performance decrements when applying a more complex rule. The
      age effect interacted with both stimulus novelty and response competition, and
      was not eliminated after controlling for basic perceptual abilities and rule
      memory. The authors suggest that older adults show category learning deficits in
      conditions that require enhanced cognitive control. These results are discussed
      in reference to the growing body of literature regarding age-related change in
      executive abilities and frontal lobe function.

PMID- 16887782
TI  - Aging and comparative search for feature differences.
AB  - In a comparative visual search experiment, two halves of a display contained
      visual primitives of various shapes and colors. These halves were identical (50%
      of trials) or contained a non-matching pair (50% of trials). Response time (RT),
      accuracy, and eye movements were measured in both young and older adults. There
      were Age Group x Display Size interactions found for RT, with older adult RT
      affected more than younger adult RT by increases in display size. This
      interaction was consistent with predictions generated by sequential-sampling
      models for RT. There were age group main effects on fixation number and fixation
      duration, but no age group main effects on accuracy, saccade amplitude, or
      measures of scan-path efficiency; this indicated that search strategies were
      similar across age groups. Overall, the results showed no special age group
      deficits for comparative visual search.

PMID- 16887783
TI  - Aging, encoding fluency, and metacognitive monitoring.
AB  - Encoding fluency (how rapidly one generates a mediator for a new association) may
      be a cue used to judge one's own learning. To evaluate age differences in
      utilization of this cue, older and younger adults were instructed to use
      interactive imagery to study paired associates, pressing a button to indicate
      when an image had been formed for a given pair. A judgment of learning (JOL) was
      also made immediately after each pair had been studied. Hence, at least two cues
      pertaining to encoding fluency-whether an image had been formed (a diagnostic
      cue) and the latency of formation (a nondiagnostic one)-were available when
      making JOLs. Age equivalence was found in JOL accuracy, and JOLs for both age
      groups were positively related to imagery formation and were negatively related
      to the latency of image formation. Moreover, subjectively judged latency
      correlated higher with JOLs than actual (objective) latency, supporting the
      hypothesis that perceived fluency is a cue used in constructing JOLs.

PMID- 16887784
TI  - Gender effects on reaction time variability and trial-to-trial performance: reply
      to Deary and Der (2005).
AB  - Deary and Der (2005) reported significant gender effects on intraindividual
      variability in choice reaction time (CRT), and suggested several potential
      causes. In their procedure it was not possible to examine RTs on a trial-to-trial
      basis. We therefore investigate an additional possible cause: that men and women
      differ in their rate of performance improvement across trials, creating an
      apparent difference in variability. Using data from a large online CRT study, we
      replicate the finding that women are more variable in RT than men. However, we
      also demonstrate an interaction between gender and trial number for RT: women
      were initially slower than men, but became faster than men across a block. When
      the first two trials of the block are excluded, the gender effects on RT
      variability disappear.

PMID- 16887785
TI  - Episodic encoding in normal aging: attentional resources hypothesis extended to
      musical material.
AB  - The goal of the present study was to examine age-related changes in musical
      episodic memory for novel tunes. This was conducted by manipulating the encoding
      condition in a recognition paradigm. After receiving memory instructions
      (intentional condition), older and younger participants obtained equivalent hits.
      In contrast, when intentional encoding was accompanied by a dancing judgment
      (dancing + intentional condition), the recognition performance of the older
      persons was severely impaired. Impaired recognition was also found when
      participants only judged the excerpts without being instructed to memorize them
      (dancing judgment condition). Although older participants demonstrated a
      preserved ability to perform the dancing judgment on its own, this ability was
      not optimal and likely precluded the initiation of more elaborate encoding
      strategies. These results suggest that asking older persons to divide their
      attention in the study phase reduces the quality of their musical encoding. Given
      this extension to musical material, we discuss the notion that the age-related
      attentional resource decline appears to be domain-general rather than specific to
      verbal material.

PMID- 16887786
TI  - Heterogeneity in verbal memory: a marker of preclinical Alzheimer's disease?
AB  - Demonstrations of memory changes in those at risk for Alzheimer's disease by the
      presence of the APOE e4 allele have been inconsistent to date. The present study
      went beyond traditional analyses of central tendency (i.e., group differences on
      mean test scores) and also conducted distribution analyses to search for subtle
      cognitive differences in subgroups of normal-functioning elderly persons with the
      APOE e4 genotype. The results of the study revealed that (a) the e4 and non-e4
      groups failed to differ in terms of their mean scores on tests of memory and
      verbal skills; and (b) relative to the non-e4 group, the e4 subjects had
      significantly greater heterogeneity of variance on the memory measures but not on
      fundamental verbal skills. Logistic regression analyses indicated that the
      discrepancy in scores on the memory measures was a significant predictor of
      genotype group membership (82% correct classification rate). Implications of
      these findings for the detection of a preclinical phase of AD are discussed.

PMID- 16887787
TI  - The relation of lifetime cognitive activity and lifetime access to resources to
      late-life cognitive function in older African Americans.
AB  - Research in older Caucasians has demonstrated that cognitive activity is related
      to cognitive function in late adulthood. Knowledge of this association is limited
      in older minority populations. We examined the relation of cognitive activity and
      access to cognitive resources, with cognitive function in a group of 108 older
      African Americans. We constructed two scales to measure the frequency of
      cognitive activity and the presence of resources that promote cognitive activity
      during early and late life. Both measures had high internal consistency and the
      cognitive activity scale had adequate temporal stability over a 4-week interval.
      In analyses that controlled for age and education, more frequent lifetime
      cognitive activity was related to current cognitive function, but lifetime
      cognitive resources only approached significance. The results suggest that both
      measures are psychometrically sound in a minority population and that lifetime
      cognitive activity may contribute to current cognitive function in African
      Americans.

PMID- 16887788
TI  - Covariates of production and perseveration on tests of phonemic, semantic and
      alternating fluency in normal aging.
AB  - Standard measures of phonemic and semantic fluency, as well as fluency measures
      that impose additional demands upon set-switching were administered to younger
      and older adults. No age effect was found for total output on semantic fluency,
      while older participants generated significantly more responses relative to their
      younger counterparts on the phonemic measure. However, older adults made
      significantly more perseverative errors on both these measures. For tests of
      alternating fluency, only where participants were required to switch between two
      semantic dimensions, was an age deficit observed. Although the correlation
      between phonemic repetitions and age remained significant when performance on the
      Digit Symbol Test or a measure of fluid intelligence was partialled out, age
      effects for semantic repetitions and semantic alternating fluency were
      substantially reduced. The age benefit for number of correct responses upon
      phonemic fluency was significantly attenuated when a measure of crystallized
      intelligence was entered as a control variable. The theoretical and practical
      implications of these results are discussed.

PMID- 16887790
TI  - Sex differences in cognition are stable over a 10-year period in adulthood and
      old age.
AB  - Sex differences in declarative memory and visuospatial ability are robust in
      cross-sectional studies. The present longitudinal study examined whether sex
      differences in cognition were present over a 10-year period, and whether age
      modified the magnitude of sex differences. Tests assessing episodic and semantic
      memory, and visuospatial ability were administered to 625 nondemented adults
      (initially aged 35-80 years), participating in the population-based Betula study
      at two follow-up occasions. There was stability of sex differences across five
      age groups and over a 10-year period. Women performed at a higher level than men
      on episodic recall, face and verbal recognition, and semantic fluency, whereas
      men performed better than women on a task-assessing, visuospatial ability. Sex
      differences in cognitive functions are stable over a 10-year period and from 35
      to 90 years of age.

PMID- 16887789
TI  - Aging and repetition priming for targets and distracters in a working memory
      task.
AB  - A combined working memory/repetition priming task was administered to 13 young
      (mean age 23) and 13 elderly (mean age 69) adults. Each participant memorized a
      sample target face at the beginning of a trial and then determined whether each
      of 13 serially presented test faces matched the sample target. In each trial,
      both the target and one particular distracter face were repeated during the test
      phase. Within-trial repetition priming effects indicated the contribution of
      implicit memory to task performance. Response times decreased as items were
      tested repeatedly within a trial, but this decrement was greater for distracters
      than for targets. Young and older participants were equally accurate at
      identifying targets, but elderly were slightly less accurate for distracters.
      Elderly participants showed repetition priming effects for both targets and
      distracters, while the young showed such effects only for distracters. The
      results suggest that active maintenance in working memory, but not inhibition or
      rejection of distracters, may suppress implicit memory systems.

PMID- 16887791
TI  - Accounting for cognitive aging: context processing, inhibition or processing
      speed?
AB  - Age-related deficits in context processing were examined in relationship to two
      predominant theories of cognitive aging (the Inhibitory Deficit and Processing
      Speed Models). Older and younger adults completed a measure of context processing
      (AX Continuous Performance Test (CPT) task) as well as a computerized battery of
      inhibitory tasks: Stroop, garden path sentences, go no-go, and the stop-signal
      paradigm. Participants also completed a simple processing speed task. After
      controlling for baseline differences in processing speed, age effects were
      detected on the AX-CPT. Smaller, but significant age effects were noted on the
      Stroop and stop-signal tasks, but no significant age effects were found on the
      garden path sentence and go no-go tasks. Intertask correlations were weak,
      providing little evidence for a homogenous or uniform construct of inhibition.
      The sensitivity of the AX-CPT to cognitive aging is discussed in the context of
      existing theories of cognitive aging. The authors suggest that deficits in
      context processing and utilization may underlie cognitive aging phenomena.

PMID- 16887792
TI  - Short- and long-term implicit memory in aging and Alzheimer's disease.
AB  - Implicit memory processes were investigated via picture naming in healthy young
      and older adults and in persons with mild Alzheimer's disease (AD). Repetition
      priming in picture-naming was intact in all groups over the course of a short
      retention interval (seconds), and only the AD group revealed a deficit over a
      longer interval (72 hours). In addition, the AD group showed impaired procedural
      memory, with no benefit of practice on picture-naming. Impaired long-term priming
      was related to severity of AD. Both theoretical and methodological implications
      are discussed.

PMID- 16887793
TI  - Emotional experience and facial expression in Alzheimer's disease.
AB  - Emotional experiences and facial muscle activity of individuals with Alzheimer's
      Disease (AD) (n = 13) and healthy elderly control subjects (n = 21) were measured
      while viewing emotion-eliciting images. Alzheimer's disease and control groups
      rated their emotional experiences similarly and in the expected directions on
      dimensions of valence and arousal. Change in corrugator activity while viewing
      images, compared to baseline, was comparable across groups and was greatest while
      viewing negative images. Change in zygomatic activity, however, was significantly
      different between AD and control groups, with AD subjects demonstrating an
      inverted pattern of activity compared to controls. These findings are discussed
      as possible consequences of frontal cortical system involvement accompanying the
      disease process.

PMID- 16887794
TI  - Evaluation of approaches to generation of tissue-specific knock-in mice.
AB  - We explored three approaches to create tissue-specific knock-in mice by
      generating knock-in mice in which a substrate-docking site of the PDK1 protein
      kinase was ablated in Cre-expressing tissues in a way that prevented activation
      of one of its substrates, p70 ribosomal S6 kinase (S6K), but not another (protein
      kinase B (PKB)). Employing two of the approaches, termed the "heterozygous" and
      "minigene" methods, we generated mice in which Cre-expressing skeletal and
      cardiac muscle produced the mutant rather than wild type PDK1. Consistent with
      this, injection of these mice with insulin only induced activation of PKB but not
      S6K in muscle tissues. We have also demonstrated that insulin-stimulated glucose
      uptake proceeds normally in knock-in mice, consistent with the notion that PKB
      mediates this process. In contrast to conditional knock-out of PDK1 in muscle,
      the knock-in mice did not develop dilated cardiomyopathy, suggesting that PKB
      plays a key role in protecting mice from heart failure. The third knock-in
      strategy that was evaluated, termed the "inversion" method, did not proceed with
      high efficiency. We discuss the merits and disadvantages of each of the
      conditional knock-in approaches, along with the applications for which they may
      be most suited, and suggest how they could be further refined.

PMID- 16887795
TI  - Deletion of the transmembrane transporter ABCG1 results in progressive pulmonary
      lipidosis.
AB  - We show that mice lacking the ATP-binding cassette transmembrane transporter
      ABCG1 show progressive and age-dependent severe pulmonary lipidosis that
      recapitulates the phenotypes of different respiratory syndromes in both humans
      and mice. The lungs of chow-fed Abcg1(-/-) mice, >6-months old, exhibit extensive
      subpleural cellular accumulation, macrophage, and pneumocyte type 2 hypertrophy,
      massive lipid deposition in both macrophages and pneumocytes and increased levels
      of surfactant. No such abnormalities are observed at 3 months of age. However,
      gene expression profiling reveals significant changes in the levels of mRNAs
      encoding key genes involved in lipid metabolism in both 3- and 8-month-old Abcg1(
      /-) mice. These data suggest that the lungs of young Abcg1(-/-) mice maintain
      normal lipid levels by repressing lipid biosynthetic pathways and that such
      compensation is inadequate as the mice mature. Studies with A-549 cells, a model
      for pneumocytes type 2, demonstrate that overexpression of ABCG1 specifically
      stimulates the efflux of cellular cholesterol by a process that is dependent upon
      phospholipid secretion. In addition, we demonstrate that Abcg1(-/-), but not wild
      type macrophages, accumulate cholesterol ester droplets when incubated with
      surfactant. Together, these data provide a mechanism to explain the lipid
      accumulation in the lungs of Abcg1(-/-)mice. In summary, our results demonstrate
      that ABCG1 plays essential roles in pulmonary lipid homeostasis.

PMID- 16887796
TI  - Stat3 mediates interleukin-6 [correction of interelukin-6] inhibition of human
      endothelial nitric-oxide synthase expression.
AB  - Chronic activation of the acute phase response (APR) is associated with
      atherosclerosis. Elevated levels of interleukin-6, the major inducer of the APR,
      are associated with an increased risk of cardiovascular events. One of the
      clinical hallmarks of atherogenesis is endothelial dysfunction, characterized by
      a decrease in endothelial production of nitric oxide (NO). We hypothesized that
      interleukin-6 (IL-6) decreases endothelial NO synthase (eNOS) expression. We now
      show that IL-6 treatment of human aortic endothelial cells (HAEC) decreases
      steady-state levels of human eNOS mRNA and protein. This decrease in eNOS
      expression is caused in part by IL-6 inhibition of transactivation of the human
      eNOS promoter. To explore the mechanism by which IL-6 affects eNOS expression, we
      examined activation of signal transducer and transactivator-3 (Stat3). The IL-6
      receptor (IL-6R) is expressed in HAEC, and Stat3 is phosphorylated in response to
      IL-6 stimulation of the IL-6R. We identified four consensus sequences for Stat3
      binding (SIE) in the eNOS promoter at positions -1520, -1024, -840, and -540.
      Transfection of eNOS promoter mutants revealed that the SIE at -1024 mediates
      Stat3 inhibition of eNOS promoter activity. Gel-shift analysis of nuclear
      extracts from HAEC treated with IL-6 confirms that Stat3 binds to a complex
      containing the SIE at -1024. RNA silencing of STAT3 blocks the inhibitory effect
      of IL-6 on eNOS expression. Our data show that IL-6 has direct effects upon
      endothelial cells, inhibiting eNOS expression in part through Stat3. Decreased
      levels of eNOS may be an important component of the pro-atherogenic effect of the
      APR.

PMID- 16887798
TI  - The iron-sulfur cluster-free hydrogenase (Hmd) is a metalloenzyme with a novel
      iron binding motif.
AB  - The iron-sulfur cluster-free hydrogenase (Hmd) from methanogenic archaea harbors
      an iron-containing cofactor of yet unknown structure. X-ray absorption
      spectroscopy of the active, as isolated enzyme from Methanothermobacter
      marburgensis (mHmd) and of the active, reconstituted enzyme from
      Methanocaldococcus jannaschii (jHmd) revealed the presence of mononuclear iron
      with two CO, one sulfur and one or two N/O in coordination distance. In jHmd, the
      single sulfur ligand is most probably provided by Cys176, as deduced from a
      comparison of the activity and of the x-ray absorption and Mossbauer spectra of
      the enzyme mutated in any of the three conserved cysteines. In the isolated Hmd
      cofactor, two CO, one sulfur, and two nitrogen/oxygen atoms coordinate the iron,
      the sulfur ligand being most probably provided by mercaptoethanol, which is
      absolutely required for the extraction of the iron-containing cofactor from the
      holoenzyme and for the stabilization of the extracted cofactor. In active mHmd
      holoenzyme, the number of iron ligands increased by one when one of the Hmd
      inhibitors (CO or KCN) were present, indicating that in active Hmd, the iron
      contains an open coordination site, which is proposed to be the site of H2
      interaction.

PMID- 16887797
TI  - Substrate specificity of the adenylation enzyme SgcC1 involved in the
      biosynthesis of the enediyne antitumor antibiotic C-1027.
AB  - C-1027 is an enediyne antitumor antibiotic composed of a chromophore with four
      distinct chemical moieties, including an (S)-3-chloro-4,5-dihydroxy-beta
      phenylalanine moiety that is derived from l-alpha-tyrosine. SgcC4, a novel
      aminomutase requiring no added co-factor that catalyzes the formation of the
      first intermediate (S)-beta-tyrosine and subsequently SgcC1 homologous to
      adenylation domains of nonribosomal peptide synthetases, was identified as
      specific for the SgcC4 product and did not recognize any alpha-amino acids. To
      definitively establish the substrate for SgcC1, a full kinetic characterization
      of the enzyme was performed using amino acid-dependent ATP-[(32)P]PP(i) exchange
      assay to monitor amino acid activation and electrospray ionization-Fourier
      transform mass spectroscopy to follow the loading of the activated beta-amino
      acid substrate to the peptidyl carrier protein SgcC2. The data establish (S)-beta
      tyrosine as the preferred substrate, although SgcC1 shows promiscuous activity
      toward aromatic beta-amino acids such as beta-phenylalanine, 3-chloro-beta
      tyrosine, and 3-hydroxy-beta-tyrosine, but all were <50-fold efficient. A
      putative active site mutant P571A adjacent to the invariant aspartic acid residue
      of all alpha-amino acid-specific adenylation domains known to date was prepared
      as a preliminary attempt to probe the substrate specificity of SgcC1; however the
      mutation resulted in a loss of activity with all substrates except (S)-beta
      tyrosine, which was 142-fold less efficient relative to the wild-type enzyme. In
      total, SgcC1 is now confirmed to catalyze the second step in the biosynthesis of
      the (S)-3-chloro-4,5-dihydroxy-beta-phenylalanine moiety of C-1027, presenting
      downstream enzymes with an (S)-beta-tyrosyl-S-SgcC2 thioester substrate, and
      represents the first beta-amino acid-specific adenylation enzyme characterized
      biochemically.

PMID- 16887799
TI  - Inhibition of cyclin-dependent kinase 5 activity protects pancreatic beta cells
      from glucotoxicity.
AB  - Type 2 diabetes (T2D) and Alzheimer disease are degenerative diseases that may
      share common pathophysiologic mechanisms. Neuronal dysfunction in Alzheimer
      patients has been linked to overactivity of the cyclin-dependent kinase 5 (CDK5)
      and its activator p35. Both of these proteins are expressed in the insulin
      producing beta cells of the pancreas. Further, glucose enhances p35 gene
      expression, promoting the formation of active p35/CDK5 complexes that regulate
      the expression of the insulin gene. In T2D, chronic elevations of glucose,
      glucotoxicity, impair beta cell function. We therefore postulated that CDK5 and
      p35 may be responsible for this beta cell impairment and that inhibition of CDK5
      might have a beneficial effect. To test this hypothesis, the pancreatic cell line
      INS-1 was selected as a known in vitro model of glucotoxicity, and roscovitine
      (10 mum) was used as a CDK5 inhibitor. Chronic exposure of INS-1 cells to high
      glucose (20-30 mm) reduced both insulin mRNA levels and the activity of an
      insulin promoter reporter gene. Inhibition of CDK5 prevented this decrease of
      insulin gene expression. We used DNA binding (gel shift) assays and Western
      immunoblots to demonstrate that cellular levels of the transcription factor PDX
      1, normally decreased by glucotoxicity, were preserved with CDK5 inhibition, as
      was the binding of PDX-1 to the insulin promoter. Analyses of nuclear and
      cytoplasmic PDX-1 protein levels revealed that CDK5 inhibition restores nuclear
      PDX-1, without affecting its cytoplasmic concentration, suggesting that CDK5
      regulates the nuclear/cytoplasm partitioning of PDX-1. Using a Myc-tagged PDX-1
      construct, we showed that the translocation of PDX-1 from the nucleus to the
      cytoplasm during glucotoxic conditions was prevented when CDK5 was inhibited.
      These studies indicate that CDK5 plays a role in the loss of beta cell function
      under glucotoxic conditions and that CDK5 inhibitors could have therapeutic value
      for T2D.

PMID- 16887800
TI  - Immunophilin-like TWISTED DWARF1 modulates auxin efflux activities of Arabidopsis
      P-glycoproteins.
AB  - The immunophilin-like protein TWISTED DWARF1 (TWD1/FKBP42) has been shown to
      physically interact with the multidrug resistance/P-glycoprotein (PGP) ATP
      binding cassette transporters PGP1 and PGP19 (MDR1). Overlapping phenotypes of
      pgp1/pgp19 and twd1 mutant plants suggested a positive regulatory role of TWD1 in
      PGP-mediated export of the plant hormone auxin, which controls plant development.
      Here, we provide evidence at the cellular and plant levels that TWD1 controls PGP
      mediated auxin transport. twd1 and pgp1/pgp19 cells showed greatly reduced export
      of the native auxin indole-3-acetic acid (IAA). Constitutive overexpression of
      PGP1 and PGP19, but not TWD1, enhanced auxin export. Coexpression of TWD1 and
      PGP1 in yeast and mammalian cells verified the specificity of the regulatory
      effect. Employing an IAA-specific microelectrode demonstrated that IAA influx in
      the root elongation zone was perturbed and apically shifted in pgp1/pgp19 and
      twd1 roots. Mature roots of pgp1/pgp19 and twd1 plants revealed elevated levels
      of free IAA, which seemed to account for agravitropic root behavior. Our data
      suggest a novel mode of PGP regulation via FK506-binding protein-like
      immunophilins, implicating possible alternative strategies to overcome multidrug
      resistance.

PMID- 16887801
TI  - Mapping conformational changes of a type IIb Na+/Pi cotransporter by voltage
      clamp fluorometry.
AB  - The fluorescence of a fluorophore depends on its environment, and if attached to
      a protein it may report on conformational changes. We have combined two-electrode
      voltage clamp with simultaneous fluorescence measurements to detect
      conformational changes in a type IIb Na(+)/P(i) cotransporter expressed in
      Xenopus oocytes. Four novel Cys, labeled with a fluorescent probe, yielded
      voltage- and substrate-dependent changes in fluorescence (F). Neither Cys
      substitution nor labeling significantly altered the mutant electrogenic
      properties. Different F responses to voltage and substrate were recorded at the
      four sites. S155C, located in an intracellular re-entrant loop in the first half
      of the protein, and E451C, located in an extracellular re-entrant loop in the
      second half of the protein, both showed Na(+), Li(+), and P(i)-dependent F
      signals. S226C and Q319C, located at opposite ends of a large extracellular loop
      in the middle of the protein, mainly responded to changes in Na(+) and Li(+).
      Hyperpolarization increased F for S155C and S226C but decreased F for Q319C and
      E451C. The labeling and F response of S155C, confirmed that the intracellular
      loop containing Ser-155 is re-entrant as it is accessible from the extracellular
      milieu. The behavior of S155C and E451C indicates a strong involvement of the two
      re-entrant loops in conformational changes during the transport cycle. Moreover,
      the data for S226C and Q319C suggest that also the large extracellular loop is
      associated with transport function. Finally, the reciprocal voltage dependences
      of the S155C-E451C and S226C-Q319C pairs suggest reciprocal conformational
      changes during the transport cycle for their respective local environments.

PMID- 16887802
TI  - Controlling electron transfer in Acyl-CoA oxidases and dehydrogenases: a
      structural view.
AB  - Plants produce a unique peroxisomal short chain-specific acyl-CoA oxidase (ACX4)
      for beta-oxidation of lipids. The short chain-specific oxidase has little
      resemblance to other peroxisomal acyl-CoA oxidases but has an approximately 30%
      sequence identity to mitochondrial acyl-CoA dehydrogenases. Two biochemical
      features have been linked to structural properties by comparing the structures of
      short chain-specific Arabidopsis thaliana ACX4 with and without a substrate
      analogue bound in the active site to known acyl-CoA oxidases and dehydrogenase
      structures: (i) a solvent-accessible acyl binding pocket is not required for
      oxygen reactivity, and (ii) the oligomeric state plays a role in substrate pocket
      architecture but is not linked to oxygen reactivity. The structures indicate that
      the acyl-CoA oxidases may encapsulate the electrons for transfer to molecular
      oxygen by blocking the dehydrogenase substrate interaction site with structural
      extensions. A small binding pocket observed adjoining the flavin adenine
      dinucleotide N5 and C4a atoms could increase the number of productive encounters
      between flavin adenine dinucleotide and O2.

PMID- 16887804
TI  - Neurotrophic factors stabilize microtubules and protect against rotenone toxicity
      on dopaminergic neurons.
AB  - Parkinson disease is characterized by the selective degeneration of dopaminergic
      (DA) neurons in substantia nigra. Long term epidemiological studies have
      implicated exposure to agricultural pesticides as a significant risk factor.
      Systemic administration of rotenone, a widely used pesticide, causes selective
      degeneration of nigral DA neurons and Parkinson disease-like symptoms in rats.
      Our previous study has shown that the microtubule depolymerizing activity of
      rotenone plays a critical role in its selective toxicity on DA neurons. Rotenone
      toxicity is mimicked by the microtubule-depolymerizing drug colchicine and
      attenuated by the microtubule-stabilizing agent taxol. Here we show that nerve
      growth factor (NGF) significantly reduced rotenone toxicity on TH(+) neurons in
      midbrain neuronal cultures. The protective effect of NGF was completely abolished
      by inhibiting the microtubule-associated protein kinase kinase (MEK) and
      partially reversed by blocking phosphatidylinositol 3-kinase. In addition, NGF
      decreased colchicine toxicity on TH(+) neurons in a manner dependent on MEK but
      not phosphatidylinositol 3-kinase. The protective effect of NGF against rotenone
      toxicity was occluded by the microtubule-stabilizing drug taxol. In a MEK
      dependent manner, NGF significantly attenuated rotenone- or colchicine-induced
      microtubule depolymerization and ensuing accumulation of vesicles in the soma and
      elevation in protein carbonyls. Moreover, other neurotrophic factors such as
      brain-derived neurotrophic factor and glia cell line-derived neurotrophic factor
      also reduced rotenone- or colchicine-induced microtubule depolymerization and
      death of TH(+) through a MEK-dependent mechanism. Thus, our results suggest that
      neurotrophic factors activate the microtubule-associated protein kinase pathway
      to stabilize microtubules, and this action significantly attenuates rotenone
      toxicity on dopaminergic neurons.

PMID- 16887803
TI  - Nitrated fatty acids: Endogenous anti-inflammatory signaling mediators.
AB  - Nitroalkene derivatives of linoleic acid (LNO2) and oleic acid (OA-NO2) are
      present; however, their biological functions remain to be fully defined. Herein,
      we report that LNO2 and OA-NO2 inhibit lipopolysaccharide-induced secretion of
      proinflammatory cytokines in macrophages independent of nitric oxide formation,
      peroxisome proliferator-activated receptor-gamma activation, or induction of heme
      oxygenase-1 expression. The electrophilic nature of fatty acid nitroalkene
      derivatives resulted in alkylation of recombinant NF-kappaB p65 protein in vitro
      and a similar reaction with p65 in intact macrophages. The nitroalkylation of p65
      by fatty acid nitroalkene derivatives inhibited DNA binding activity and
      repressed NF-kappaB-dependent target gene expression. Moreover, nitroalkenes
      inhibited endothelial tumor necrosis factor-alpha-induced vascular cell adhesion
      molecule 1 expression and monocyte rolling and adhesion. These observations
      indicate that nitroalkenes such as LNO2 and OA-NO2, derived from reactions of
      unsaturated fatty acids and oxides of nitrogen, are a class of endogenous anti
      inflammatory mediators.

PMID- 16887805
TI  - Differential effects of mitochondrial heat shock protein 60 and related molecular
      chaperones to prevent intracellular beta-amyloid-induced inhibition of complex IV
      and limit apoptosis.
AB  - Defects in mitochondrial oxidative metabolism, in particular decreased activity
      of cytochrome c oxidase, have been reported in Alzheimer disease tissue and in
      cultured cells that overexpress amyloid precursor protein. Mitochondrial
      dysfunction contributes to neurodegeneration in Alzheimer disease partly through
      formation of reactive oxygen species and the release of sequestered molecules
      that initiate programmed cell death pathways. The heat shock proteins (HSP) are
      cytoprotective against a number of stressors, including accumulations of
      misfolded proteins and reactive oxygen species. We reported on the property of
      Hsp70 to protect cultured neurons from cell death caused by intraneuronal beta
      amyloid. Here we demonstrate that Hsp60, Hsp70, and Hsp90 both alone and in
      combination provide differential protection against intracellular beta-amyloid
      stress through the maintenance of mitochondrial oxidative phosphorylation and
      functionality of tricarboxylic acid cycle enzymes. Notably, beta-amyloid was
      found to selectively inhibit complex IV activity, an effect selectively
      neutralized by Hsp60. The combined effect of HSPs was to reduce the free radical
      burden, preserve ATP generation, decrease cytochrome c release, and prevent
      caspase-9 activation, all important mediators of beta-amyloid-induced neuronal
      dysfunction and death.

PMID- 16887806
TI  - Homer 1 mediates store- and inositol 1,4,5-trisphosphate receptor-dependent
      translocation and retrieval of TRPC3 to the plasma membrane.
AB  - Store-operated Ca(2+) channels (SOCs) mediate receptor-stimulated Ca(2+) influx.
      Accumulating evidence indicates that members of the transient receptor potential
      (TRP) channel family are components of SOCs in mammalian cells. Agonist
      stimulation activates SOCs and TRP channels directly and by inducing
      translocation of channels in intracellular vesicles to the plasma membrane (PM).
      The mechanism of TRP channel translocation in response to store depletion and
      agonist stimulation is not known. Here we use TRPC3 as a model to show that IP(3)
      and the scaffold Homer 1 (H1) regulate the rate of translocation and retrieval of
      TRPC3 from the PM. In resting cells, TRPC3 exists in TRPC3-H1b/c-IP(3)Rs
      complexes that are located in part at the PM and in part in intracellular
      vesicles. Binding of IP(3) to the IP(3)Rs dissociates the interaction between
      IP(3)Rs and H1 but not between H1 and TRPC3 to form IP(3)Rs-TRPC3-H1b/c. TIRFM
      and biotinylation assays show robust receptor- and store-dependent translocation
      of the TRPC3 to the PM and their retrieval upon termination of cell stimulation.
      The translocation requires depletion of stored Ca(2+) and is prevented by
      inhibition of the IP(3)Rs. In HEK293, dissociating the H1b/c-IP(3)R complex with
      H1a results in TRPC3 translocation to the PM, where it is spontaneously active.
      The TRPC3-H1b/c-IP(3)Rs complex is reconstituted by infusing H1c into these
      cells. Reconstitution is inhibited by IP(3). Deletion of H1 in mice markedly
      reduces the rates of translocation and retrieval of TRPC3. Conversely, infusion
      of H1c into H1(-/-) cells eliminates spontaneous channel activity and increases
      the rate of channel activation by agonist stimulation. The effects of H1c are
      inhibited by IP(3). These findings together with our earlier studies
      demonstrating gating of TRPC3 by IP(3)Rs were used to develop a model in which
      assembly of the TRPC3-H1b/c-IP(3)Rs complexes by H1b/c mediates both the
      translocation of TRPC3-containing vesicles to the PM and gating of TRPC3 by
      IP(3)Rs.

PMID- 16887807
TI  - Interleukin-1 beta released by gp120 drives neural death through tyrosine
      phosphorylation and trafficking of NMDA receptors.
AB  - Interleukin-1beta is a proinflammatory cytokine implicated under pathological
      conditions involving NMDA receptor activation, including the AIDS dementia
      complex (HAD). No information is available on the molecular mechanisms recruited
      by native interleukin-1beta produced under this type of condition. Using a
      sandwich co-culture of primary hippocampal neurons and glia, we investigated
      whether native interleukin-1beta released by HIV-gp120-activated glia (i) affects
      NMDAR functions and (ii) the relevance on neuronal spine density and survival,
      two specific traits of HAD. Increased phosphorylation of NR2B Tyr-1472 was
      observed after 24 h of exposure of neurons to 600 pm gp120. This effect occurred
      only when neurons were treated in the presence of glial cells and was abolished
      by the interleukin-1 receptor antagonist (IL-1ra). Gp120-induced phosphorylation
      of NR2B resulted in a sustained elevation of intracellular Ca(2+) in neurons and
      in a significant increase of NR2B binding to PSD95. Increased intracellular
      Ca(2+) was prevented by 10 mum ifenprodil, that selectively inhibits receptors
      containing the NR2B, by interleukin-1ra and by Ca-pYEEIE, a Src family SH2
      inhibitor peptide. These last two inhibitors, prevented also NR2B binding to
      PSD95. Finally, gp120 reduced by 35% of the total PSD95 positive spine density
      after 48 h of treatment and induced by 30% of the neuronal death. Again, both of
      these effects were blocked by Ca-pYEEIE. Altogether, our data show that gp120
      releasing interleukin-1beta from glia increases tyrosine phosphorylation of
      NMDAR. Thus, tyrosine phosphorylation may contribute to the sensitization of the
      receptor increasing its function and synaptic localization. Both of these effects
      are relevant for neurodegeneration.

PMID- 16887808
TI  - The anti-HIV-1 editing enzyme APOBEC3G binds HIV-1 RNA and messenger RNAs that
      shuttle between polysomes and stress granules.
AB  - Deoxycytidine deaminases APOBEC3G (A3G) and APOBEC3F (A3F) (members of the
      apolipoprotein B mRNA-editing catalytic polypeptide 3 family) have RNA-binding
      motifs, invade assembling human immunodeficiency virus (HIV-1), and hypermutate
      reverse transcripts. Antagonistically, HIV-1 viral infectivity factor degrades
      these enzymes. A3G is enzymatically inhibited by binding RNA within an
      unidentified large cytosolic ribonucleoprotein, implying that RNA degradation
      during reverse transcription may activate intravirion A3G at the necessary
      moment. We purified a biologically active tandem affinity-tagged A3G from human
      HEK293T cells. Mass spectrometry and coimmunoprecipitation from HEK293T and T
      lymphocyte extracts identified many RNA-binding proteins specifically associated
      with A3G and A3F, including poly(A)-binding proteins (PABPs), YB-1, Ro-La, RNA
      helicases, ribosomal proteins, and Staufen1. Most strikingly, nearly all A3G
      associated proteins were known to bind exclusively or intermittently to
      translating and/or dormant mRNAs. Accordingly, A3G in HEK293T and T lymphocyte
      extracts was almost completely in A3G-mRNA-PABP complexes that shifted reversibly
      between polysomes and dormant pools in response to translational inhibitors. For
      example arsenite, which inhibits 5'-cap-dependent translational initiation,
      shifted mRNA-A3G-PABP from polysomes into stress granules in a manner that was
      blocked and reversed by the elongation inhibitor cycloheximide.
      Immunofluorescence microscopy showed A3G-mRNA-PABP stress granules only partially
      overlapping with Staufen1. A3G coimmunoprecipitated HIV-1 RNA and many mRNAs.
      Ribonuclease released nearly all A3G-associated proteins, including A3G homo
      oligomers and A3G-A3F hetero-oligomers, but the viral infectivity factor remained
      bound. Many proteins and RNAs associated with A3G are excluded from A3G
      containing virions, implying that A3G competitively partitions into virions based
      on affinity for HIV-1 RNA.

PMID- 16887810
TI  - HIV-1 TAR RNA subverts RNA interference in transfected cells through
      sequestration of TAR RNA-binding protein, TRBP.
AB  - TAR RNA-binding protein, TRBP, was recently discovered to be an essential partner
      for Dicer and a crucial component of the RNA-induced silencing complex (RISC), a
      critical element of the RNA interference (RNAi) of the cell apparatus. Human TRBP
      was originally characterized and cloned 15 years ago based on its high affinity
      for binding the HIV-1 encoded leader RNA, TAR. RNAi is used, in part, by cells to
      defend against infection by viruses. Here, we report that transfected TAR RNA can
      attenuate the RNAi machinery in human cells. Our data suggest that TAR RNA
      sequesters TRBP rendering it unavailable for downstream Dicer-RISC complexes. TAR
      induced inhibition of Dicer-RISC activity in transfected cells was partially
      relieved by exogenous expression of TRBP.

PMID- 16887809
TI  - Lipidic antagonists to SNARE-mediated fusion.
AB  - SNARE proteins mediate the fusion of lipid bilayers by the directed assembly of
      coiled-coil domains arising from apposing membranes. We have utilized inverted
      cone-shaped lipids, antagonists of the necessary membrane deformation during
      fusion to characterize the extent and range of SNARE assembly up to the moment of
      stalk formation between bilayers. The inverted cone-shaped lipid family of acyl
      CoAs specifically inhibits the completion of fusion in an acyl-chain length
      dependent manner. Removal of acyl-CoA from the membrane relieves the inhibition
      and initiates a burst of membrane fusion with rates exceeding any point in the
      control curves lacking acyl-CoA. This burst indicates the accumulation of semi
      assembled fusion complexes. These preformed complexes are resistant to cleavage
      by botulinum toxin B and thus appear to have progressed beyond the "loosely
      zippered" state of docked synaptic vesicles. Surprisingly, application of the
      soluble domain of VAMP2, which blocks SNARE assembly by competing for binding on
      the available t-SNAREs, blocks recovery from the acyl-CoA inhibition. Thus,
      complexes formed in the presence of a lipidic antagonist to fusion are
      incompletely assembled, suggesting that the formation of tightly assembled SNARE
      pairs requires progression all the way through to membrane fusion. In this
      regard, physiologically docked exocytic vesicles may be anchored by a highly
      dynamic and potentially even reversible SNAREpin.

PMID- 16887811
TI  - Polycomb complexes and the propagation of the methylation mark at the Drosophila
      ubx gene.
AB  - Polycomb group proteins are transcriptional repressors that control many
      developmental genes. The Polycomb group protein Enhancer of Zeste has been shown
      in vitro to methylate specifically lysine 27 and lysine 9 of histone H3 but the
      role of this modification in Polycomb silencing is unknown. We show that H3
      trimethylated at lysine 27 is found on the entire Ubx gene silenced by Polycomb.
      However, Enhancer of Zeste and other Polycomb group proteins stay primarily
      localized at their response elements, which appear to be the least methylated
      parts of the silenced gene. Our results suggest that, contrary to the prevailing
      view, the Polycomb group proteins and methyltransferase complexes are recruited
      to the Polycomb response elements independently of histone methylation and then
      loop over to scan the entire region, methylating all accessible nucleosomes. We
      propose that the Polycomb chromodomain is required for the looping mechanism that
      spreads methylation over a broad domain, which in turn is required for the
      stability of the Polycomb group protein complex. Both the spread of methylation
      from the Polycomb response elements, and the silencing effect can be blocked by
      the gypsy insulator.

PMID- 16887812
TI  - Effects of oncogenic mutations and DNA response elements on the binding of p53 to
      p53-binding protein 2 (53BP2).
AB  - The tumor suppressor p53 is frequently mutated in human cancers. Upon activation
      it can induce cell cycle arrest or apoptosis. ASPP2 can specifically stimulate
      the apoptotic function of p53 but not cell cycle arrest, but the mechanism of
      enhancing the activation of pro-apoptotic genes over cell cycle arrest genes
      remains unknown. In this study, we analyzed the binding of 53BP2 (p53-binding
      protein 2, the C-terminal domain of ASPP2) to p53 core domain and various mutants
      using biophysical techniques. We found that several p53 core domain mutations
      (R181E, G245S, R249S, R273H) have different effects on the binding of DNA
      response elements and 53BP2. Further, we investigated the existence of a ternary
      complex consisting of 53BP2, p53, and DNA response elements to gain insight into
      the specific pro-apoptotic activation of p53. We found that binding of 53BP2 and
      DNA to p53 is mutually exclusive in the case of GADD45, p21, Bax, and PIG3. Both
      pro-apoptotic and non-apoptotic response elements were competed off p53 by 53BP2
      with no indication of a ternary complex.

PMID- 16887813
TI  - Excision of the Sinorhizobium meliloti group II intron RmInt1 as circles in vivo.
AB  - Excision of group II introns as circles has been described only for a few
      eukaryotic introns and little is known about the mechanisms involved, the
      relevance or consequences of the process. We report that splicing of the
      bacterial group II intron RmInt1 in vivo leads to the formation of both intron
      lariat and intron RNA circles. We determined that besides being required for the
      intron splicing reaction, the maturase domain of the intron-encoded protein also
      controls the balance between lariat and RNA intron circle production.
      Furthermore, comparison with in vitro self-splicing products indicates that in
      vivo, the intron-encoded protein appears to promote the use of a correct
      EBS1/IBS1 intron-exon interaction as well as cleavage at, or next to, the
      expected 3' splice site. These findings provide new insights on the mechanism of
      excision of group II introns as circles.

PMID- 16887814
TI  - Identification and characterization of the CD226 gene promoter.
AB  - CD226 is one of the main activating receptors on natural killer cells, and it can
      induce cytotoxicity to target cells through interaction with its ligands CD155 or
      CD112. CD226 is also involved in T cell differentiation, activation, and
      cytotoxicity. The expression of CD226 on natural killer cells and T cells can be
      regulated by cytokines and chemical stimuli; however, the mechanism of the
      regulation of the CD226 gene is still unknown. In this study, we have identified
      two promoters in the human CD226 gene named P1 and P2, which are located at -810
      to -287 bp and +33 to +213 bp, respectively, and a negative regulation element
      between P1 and P2. Both P1 and P2 can be regulated by phorbol ester (12-O
      tetradecanoylphorbol-13-acetate) and calcium ionophore (A23187). Bioinformatics
      analysis shows that, within this CD226 gene region, there are putative binding
      sites for transcription factors AP-1, Sp1, PEA3, and Ets-1. We have found that
      transcription factor activating protein-1 (AP-1) can up-regulate CD226 promoters
      P1 and P2 in human hepatocarcinoma cells, a hepatocarcinoma cell line with low
      expression of endogenous AP-1 and Ets-1. Interestingly, the transcription factor
      Ets-1 promotes AP-1-induced P2 activity but inhibits AP-1-induced P1 activity for
      which a 10-bp AP-1/Ets-1 composite site (CCTTCCTTCC) in P1 may be responsible.

PMID- 16887815
TI  - The Na+:Cl- cotransporter is activated and phosphorylated at the amino-terminal
      domain upon intracellular chloride depletion.
AB  - The renal Na(+):Cl(-) cotransporter rNCC is mutated in human disease, is the
      therapeutic target of thiazide-type diuretics, and is clearly involved in
      arterial blood pressure regulation. rNCC belongs to an electroneutral cation
      coupled chloride cotransporter family (SLC12A) that has two major branches with
      inverse physiological functions and regulation: sodium-driven cotransporters (NCC
      and NKCC1/2) that mediate cellular Cl(-) influx are activated by phosphorylation,
      whereas potassium-driven cotransporters (KCCs) that mediate cellular Cl(-) efflux
      are activated by dephosphorylation. A cluster of three threonine residues at the
      amino-terminal domain has been implicated in the regulation of NKCC1/2 by
      intracellular chloride, cell volume, vasopressin, and WNK/STE-20 kinases. Nothing
      is known, however, about rNCC regulatory mechanisms. By using rNCC heterologous
      expression in Xenopus laevis oocytes, here we show that two independent
      intracellular chloride-depleting strategies increased rNCC activity by 3-fold.
      The effect of both strategies was synergistic and dose-dependent. Confocal
      microscopy of enhanced green fluorescent protein-tagged rNCC showed no changes in
      rNCC cell surface expression, whereas immunoblot analysis, using the R5-anti
      NKCC1-phosphoantibody, revealed increased phosphorylation of rNCC amino-terminal
      domain threonine residues Thr(53) and Thr(58). Elimination of these threonines
      together with serine residue Ser(71) completely prevented rNCC response to
      intracellular chloride depletion. We conclude that rNCC is activated by a
      mechanism that involves amino-terminal domain phosphorylation.

PMID- 16887816
TI  - Effect of TRB3 on insulin and nutrient-stimulated hepatic p70 S6 kinase activity.
AB  - Insulin and nutrients activate hepatic p70 S6 kinase (S6K1) to regulate protein
      synthesis. Paradoxically, activation of S6K1 also leads to the development of
      insulin resistance. In this study, we investigated the effect of TRB3, which acts
      as an endogenous inhibitor of Akt, on S6K1 activity in vitro and in vivo. In
      cultured cells, overexpression of TRB3 completely inhibited insulin-stimulated
      S6K1 activation by mammalian target of rapamycin, whereas knockdown of endogenous
      TRB3 increased both basal and insulin-stimulated activity. In C57BL/6 mice,
      adenoviral overexpression of TRB3 inhibited insulin-stimulated activation of
      hepatic S6K1. In contrast, overexpression of TRB3 did not inhibit nutrient
      stimulated S6K1 activity. We also investigated the effect of starvation, feeding,
      or insulin treatment on TRB3 levels and S6K1 activity in the liver of C57BL/6 and
      db/db mice. Both insulin and feeding activate S6K1 in db/db mice, but only
      insulin activates in the C57BL/6 strain. TRB3 levels were 3.5-fold higher in
      db/db mice than C57BL/6 mice and were unresponsive to feeding or insulin, whereas
      both treatments reduced TRB3 in C57BL/6 mice. Akt was activated by insulin alone
      in the C57BL/6 strain and but not in db/db mice. Both insulin and feeding
      activated mammalian target of rapamycin similarly in these mice; however, feeding
      was unable to activate the downstream target S6K1 in C57BL/6 mice. These results
      suggest that the nutrient excess in the hyperphagic, hyperinsulinemic db/db mouse
      primes the hepatocyte to respond to nutrients resulting in elevated S6K1
      activity. The combination of elevated TRB3 and constitutive S6K1 activity results
      in decreased insulin signaling via the IRS-1/phosphatidylinositol 3-kinase/Akt
      pathway.

PMID- 16887817
TI  - Requirement for Map2k1 (Mek1) in extra-embryonic ectoderm during placentogenesis.
AB  - Map2k1(-/-) embryos die at mid-gestation from abnormal development and
      hypovascularization of the placenta. We now show that this phenotype is
      associated with a decreased labyrinth cell proliferation and an augmented cell
      apoptosis. Although the activation of MAP2K1 and MAP2K2 is widespread in the
      labyrinthine region, MAPK1 and MAPK3 activation is restricted to the cells lining
      the maternal sinuses, suggesting an important role for the ERK/MAPK cascade in
      these cells. In Map2k1(-/-) placenta, ERK/MAPK cascade activation is perturbed.
      Abnormal localization of the syncytiotrophoblasts is also observed in Map2k1(-/-)
      placenta, even though this cell lineage is specified at the correct time during
      placentogenesis. The placental phenotype can be rescued in tetraploid
      experiments. In addition, Map2k1-specific deletion in the embryo leads to normal
      embryo development and to the birth of viable Map2k1(-/-) mice. Altogether, these
      data enlighten the essential role of Map2k1 in extra-embryonic ectoderm during
      placentogenesis. In the embryo, the Map2k1 gene function appears dispensable.

PMID- 16887818
TI  - Disruption of early proximodistal patterning and AVE formation in Apc mutants.
AB  - In the postimplantation mouse embryo, axial patterning begins with the
      restriction of expression of a set of genes to the distal visceral endoderm
      (DVE). This proximodistal (PD) axis is subsequently transformed into an
      anteroposterior axis as the VE migrates anteriorly to form the anterior visceral
      endoderm (AVE). Both Nodal and Wnt signaling pathways are involved in these
      events. We show here that loss of function in the adenomatous polyposis coli gene
      (Apc) leads to constitutive beta-catenin activity that induces a proximalization
      of the epiblast with the activation of a subset of posterior mesendodermal genes,
      and loss of ability to induce the DVE. The loss of some DVE genes such as Hex and
      goosecoid is rescued in chimeras where only the epiblast was wild type; however,
      these DVE markers were no longer restricted distally but covered the entire
      epiblast. Thus, the Apc gene is needed in both embryonic and extraembryonic
      lineages for normal PD patterning around implantation, suggesting that early
      restricted activation of the Wnt pathway may be important for initiating axial
      asymmetries. In addition, we found that nuclear beta-catenin and other molecular
      markers are asymmetrically expressed by 4.5 days.

PMID- 16887819
TI  - Analysis of cell migration, transdifferentiation and apoptosis during mouse
      secondary palate fusion.
AB  - Malformations in secondary palate fusion will lead to cleft palate, a common
      human birth defect. Palate fusion involves the formation and subsequent
      degeneration of the medial edge epithelial seam. The cellular mechanisms
      underlying seam degeneration have been a major focus in the study of
      palatogenesis. Three mechanisms have been proposed for seam degeneration: lateral
      migration of medial edge epithelial cells; epithelial-mesenchymal trans
      differentiation; and apoptosis of medial edge epithelial cells. However, there is
      still a great deal of controversy over these proposed mechanisms. In this study,
      we established a [Rosa26<-->C57BL/6] chimeric culture system, in which a Rosa26
      originated ;blue' palatal shelf was paired with a C57BL/6-derived ;white' palatal
      shelf. Using this organ culture system, we observed the migration of medial edge
      epithelial cells to the nasal side, but not to the oral side. We also observed an
      anteroposterior migration of medial edge epithelial cells, which may play an
      important role in posterior palate fusion. To examine epithelial-mesenchymal
      transdifferentiation during palate fusion, we bred a cytokeratin 14-Cre
      transgenic line into the R26R background. In situ hybridization showed that the
      Cre transgene is expressed exclusively in the epithelium. However, beta
      galactosidase staining gave extensive signals in the palatal mesenchymal region
      during and after palate fusion, demonstrating the occurrence of an epithelial
      mesenchymal transdifferentiation mechanism during palate fusion. Finally, we
      showed that Apaf1 mutant mouse embryos are able to complete palate fusion without
      DNA fragmentation-mediated programmed cell death, indicating that this is not
      essential for palate fusion in vivo.

PMID- 16887820
TI  - Milton controls the early acquisition of mitochondria by Drosophila oocytes.
AB  - Mitochondria in many species enter the young oocyte en mass from interconnected
      germ cells to generate the large aggregate known as the Balbiani body. Organelles
      and germ plasm components frequently associate with this structure. Balbiani body
      mitochondria are thought to populate the germ line, ensuring that their genomes
      will be inherited preferentially. We find that milton, a gene whose product was
      previously shown to associate with Kinesin and to mediate axonal transport of
      mitochondria, is needed to form a normal Balbiani body. In addition, germ cells
      mutant for some milton or Kinesin heavy chain (Khc) alleles transport
      mitochondria to the oocyte prematurely and excessively, without disturbing
      Balbiani body-associated components. Our observations show that the oocyte
      acquires the majority of its mitochondria by competitive bidirectional transport
      along microtubules mediated by the Milton adaptor. These experiments provide a
      molecular explanation for Balbiani body formation and, surprisingly, show that
      viable fertile offspring can be obtained from eggs in which the normal program of
      mitochondrial acquisition has been severely perturbed.

PMID- 16887821
TI  - Dual function of the Drosophila Alk1/Alk2 ortholog Saxophone shapes the Bmp
      activity gradient in the wing imaginal disc.
AB  - Wing patterning in Drosophila requires a Bmp activity gradient created by two Bmp
      ligands, Gbb and Dpp, and two Bmp type I receptors, Sax and Tkv. Gbb provides
      long-range signaling, while Dpp signals preferentially to cells near its source
      along the anteroposterior (AP) boundary of the wing disc. How each receptor
      contributes to the signaling activity of each ligand is not well understood.
      Here, we show that while Tkv mediates signals from both Dpp and Gbb, Sax exhibits
      a novel function for a Bmp type I receptor: the ability to both promote and
      antagonize signaling. Given its high affinity for Gbb, this dual function of Sax
      impacts the function of Gbb in the Bmp activity gradient more profoundly than
      does Dpp. We propose that this dual function of Sax is dependent on its receptor
      partner. When complexed with Tkv, Sax facilitates Bmp signaling, but when alone,
      Sax fails to signal effectively and sequesters Gbb. Overall, our model proposes
      that the balance between antagonizing and promoting Bmp signaling varies across
      the wing pouch, modulating the level and effective range, and, thus, shaping the
      Bmp activity gradient. This previously unknown mechanism for modulating ligand
      availability and range raises important questions regarding the function of
      vertebrate Sax orthologs.

PMID- 16887823
TI  - DIG-1, a novel giant protein, non-autonomously mediates maintenance of nervous
      system architecture.
AB  - Dedicated mechanisms exist to maintain the architecture of an animal's nervous
      system after development is completed. To date, three immunoglobulin superfamily
      members have been implicated in this process in the nematode Caenorhabditis
      elegans: the secreted two-Ig domain protein ZIG-4, the FGF receptor EGL-15 and
      the L1-like SAX-7 protein. These proteins provide crucial information for
      neuronal structures, such as axons, that allows them to maintain the precise
      position they acquired during development. Yet, how widespread this mechanism is
      throughout the nervous system, and what other types of factors underlie such a
      maintenance mechanism, remains poorly understood. Here, we describe a new
      maintenance gene, dig-1, that encodes a predicted giant secreted protein
      containing a large number of protein interaction domains. With 13,100 amino
      acids, the DIG-1 protein is the largest secreted protein identifiable in any
      genome database. dig-1 functions post-developmentally to maintain axons and cell
      bodies in place within axonal fascicles and ganglia. The failure to maintain axon
      and cell body position is accompanied by defects in basement membrane structure,
      as evidenced by electron microscopy analysis of dig-1 mutants. Expression pattern
      and mosaic analysis reveals that dig-1 is produced by muscles to maintain nervous
      system architecture, demonstrating that dig-1 functions non-autonomously to
      preserve the proper layout of neural structures. We propose that DIG-1 is a
      component of the basement membrane that mediates specific contacts between
      cellular surfaces and their environment through the interaction with a cell-type
      specific set of other maintenance factors.

PMID- 16887822
TI  - Actin capping protein alpha maintains vestigial-expressing cells within the
      Drosophila wing disc epithelium.
AB  - Tissue patterning must be translated into morphogenesis through cell shape
      changes mediated by remodeling of the actin cytoskeleton. We have found that
      Capping protein alpha (Cpa) and Capping protein beta (Cpb), which prevent
      extension of the barbed ends of actin filaments, are specifically required in the
      wing blade primordium of the Drosophila wing disc. cpa or cpb mutant cells in
      this region, but not in the remainder of the wing disc, are extruded from the
      epithelium and undergo apoptosis. Excessive actin filament polymerization is not
      sufficient to explain this phenotype, as loss of Cofilin or Cyclase-associated
      protein does not cause cell extrusion or death. Misexpression of Vestigial, the
      transcription factor that specifies the wing blade, both increases cpa
      transcription and makes cells dependent on cpa for their maintenance in the
      epithelium. Our results suggest that Vestigial specifies the cytoskeletal changes
      that lead to morphogenesis of the adult wing.

PMID- 16887824
TI  - Primordial germ cell deficiency in the connexin 43 knockout mouse arises from
      apoptosis associated with abnormal p53 activation.
AB  - Connexin 43 knockout (Cx43alpha1KO) mice exhibit germ cell deficiency, but the
      underlying cause for the germ cell defect was unknown. Using an Oct4-GFP reporter
      transgene, we tracked the distribution and migration of primordial germ cells
      (PGCs) in the Cx43alpha1KO mouse embryo. Analysis with dye injections showed PGCs
      are gap-junction-communication competent, with dye coupling being markedly
      reduced in Cx43alpha1-deficient PGCs. Time-lapse videomicroscopy and motion
      analysis showed that the directionality and speed of cell motility were reduced
      in the Cx43alpha1KO PGCs. This was observed both in E8.5 and E11.5 embryos. By
      contrast, PGC abundance did not differ between wild-type and
      heterozygous/homozygous Cx43alpha1KO embryos until E11.5, when a marked reduction
      in PGC abundance was detected in the homozygous Cx43alpha1KO embryos. This was
      accompanied by increased PGC apoptosis and increased expression of activated p53.
      Injection of alpha-pifithrin, a p53 antagonist, inhibited PGC apoptosis and
      prevented the loss of PGC. Analysis using a cell adhesion assay indicated a
      reduction in beta1-integrin function in the Cx43alpha1KO PGCs. Together with the
      abnormal activation of p53, these findings suggest the possibility of anoikis
      mediated apoptosis. Overall, these findings show Cx43alpha1 is essential for PGC
      survival, with abnormal p53 activation playing a crucial role in the apoptotic
      loss of PGCs in the Cx43alpha1KO mouse embryos.

PMID- 16887825
TI  - Slug stability is dynamically regulated during neural crest development by the F
      box protein Ppa.
AB  - The neural crest is a population of stem-cell-like precursors found only in
      vertebrates. Slug, a member of the Snail family of zincfinger transcriptional
      repressors, is a critical regulator of neural crest development and has also been
      implicated in the acquisition of invasive behavior during tumor progression.
      Despite its central role in these two important processes, little is known about
      the mechanisms that control the expression and/or activity of Slug. We
      demonstrate that Slug is a labile protein whose stability is positively
      reinforced through activation of the neural crest regulatory program. We identify
      Partner of paired (Ppa) as the F-box component of a modular E3 ligase, and show
      that it is expressed in neural crest-forming regions, and that it binds to and
      promotes ubiquitin-mediated proteasomal degradation of Slug. Misexpression of Ppa
      inhibits the formation of neural crest precursors, and Slug mutants in which Ppa
      binding has been abrogated rescue this inhibition. These results provide novel
      insight into the regulation of Slug, a protein that plays a central role in
      neural crest precursor formation, as well as in developmental and pathological
      epithelial to mesenchymal transitions.

PMID- 16887826
TI  - The autophagy-related kinase UNC-51 and its binding partner UNC-14 regulate the
      subcellular localization of the Netrin receptor UNC-5 in Caenorhabditis elegans.
AB  - UNC-51 and UNC-14 are required for the axon guidance of many neurons in
      Caenorhabditis elegans. UNC-51 is a serine/threonine kinase homologous to yeast
      Atg1, which is required for autophagy. The binding partner of UNC-51, UNC-14,
      contains a RUN domain that is predicted to play an important role in multiple Ras
      like GTPase signaling pathways. How these molecules function in axon guidance is
      largely unknown. Here we observed that, in unc-51 and unc-14 mutants, UNC-5, the
      receptor for axon-guidance protein Netrin/UNC-6, abnormally localized in neuronal
      cell bodies. By contrast, the localization of many other proteins required for
      axon guidance was undisturbed. Moreover, UNC-5 localization was normal in animals
      with mutations in the genes for axon guidance proteins, several motor proteins,
      vesicle components and autophagy-related proteins. We also found that unc-5 and
      unc-6 interacted genetically with unc-51 and unc-14 to affect axon guidance, and
      that UNC-5 co-localized with UNC-51 and UNC-14 in neurons. These results suggest
      that UNC-51 and UNC-14 regulate the subcellular localization of the Netrin
      receptor UNC-5, and that UNC-5 uses a unique mechanism for its localization; the
      functionality of UNC-5 is probably regulated by this localization.

PMID- 16887827
TI  - IKKbeta/2 induces TWEAK and apoptosis in mammary epithelial cells.
AB  - The Nuclear Factor-kappaB (NF-kappaB) family of transcription factors are
      ubiquitously expressed and control a wide range of cellular responses, including
      apoptosis, proliferation, differentiation, inflammation and immunity. Here, we
      investigated the function of the NF-kappaB upstream regulator IkappaB kinase
      2/beta (IKK2) in apoptosis regulation in the normal physiological setting of
      regressing mammary gland. Conditional deletion of the gene encoding IKK2
      resulted, surprisingly, in delayed apoptosis and remodelling, and abrogation of
      caspase 3 cleavage. This failure to induce involution was associated with reduced
      expression, within 24 hours of involution, of the death receptor (DR) ligand TNF
      and its receptor TNFR1, which are known NF-kappaB targets. This was associated
      with elevated levels of active AKT and phosphorylated FOXO3a. Furthermore, we
      show that expression of TWEAK, another DR ligand, is dramatically downregulated,
      even in heterozygous IKK2 mammary glands. Unlike other DR ligands, the TWEAK
      promoter has six consensus FOXO-binding sites, further suggesting that it is
      differentially regulated. Interestingly, a cleaved form of TWEAK is upregulated
      during involution. This unexpected function of the IKK2/NF-kappaB pathway as a
      regulator of TWEAK expression and inducer of apoptosis has significant
      consequences for future therapeutic approaches for cancer and inflammatory
      diseases.

PMID- 16887829
TI  - Bone morphogenetic protein receptor 1A signaling is dispensable for hematopoietic
      development but essential for vessel and atrioventricular endocardial cushion
      formation.
AB  - Bone morphogenetic protein 4 (BMP4) is crucial for the formation of FLK1
      expressing (FLK1(+)) mesodermal cells. To further define the requirement for BMP
      signaling in the differentiation of blood, endothelial and smooth muscle cells
      from FLK1(+) mesoderm, we inactivated Alk3 (Bmpr1a) in FLK1(+) cells by crossing
      Alk3(floxed/floxed) and Flk1(+/Cre)Alk3(+/floxed) mice. Alk3 conditional knockout
      (CKO) mice died between E10.5 and E11.5. Unexpectedly, Alk3 CKO embryos did not
      show any hematopoietic defects. However, Alk3 CKO embryos displayed multiple
      abnormalities in vascular development, including vessel remodeling and
      maturation, which contributed to severe abdominal hemorrhage. Alk3 CKO embryos
      also displayed defects in atrioventricular canal (AVC) endocardial cushion
      formation in the heart. Collectively, our studies indicate a crucial role for
      ALK3 in vessel remodeling, vessel integrity and endocardial cushion formation
      during the development of the circulation system.

PMID- 16887828
TI  - DNA methylation is a primary mechanism for silencing postmigratory primordial
      germ cell genes in both germ cell and somatic cell lineages.
AB  - DNA methylation is necessary for the silencing of endogenous retrotransposons and
      the maintenance of monoallelic gene expression at imprinted loci and on the X
      chromosome. Dynamic changes in DNA methylation occur during the initial stages of
      primordial germ cell development; however, all consequences of this epigenetic
      reprogramming are not understood. DNA demethylation in postmigratory primordial
      germ cells coincides with erasure of genomic imprints and reactivation of the
      inactive X chromosome, as well as ongoing germ cell differentiation events. To
      investigate a possible role for DNA methylation changes in germ cell
      differentiation, we have studied several marker genes that initiate expression at
      this time. Here, we show that the postmigratory germ cell-specific genes Mvh,
      Dazl and Scp3 are demethylated in germ cells, but not in somatic cells. Premature
      loss of genomic methylation in Dnmt1 mutant embryos leads to early expression of
      these genes as well as GCNA1, a widely used germ cell marker. In addition, GCNA1
      is ectopically expressed by somatic cells in Dnmt1 mutants. These results provide
      in vivo evidence that postmigratory germ cell-specific genes are silenced by DNA
      methylation in both premigratory germ cells and somatic cells. This is the first
      example of ectopic gene activation in Dnmt1 mutant mice and suggests that dynamic
      changes in DNA methylation regulate tissue-specific gene expression of a set of
      primordial germ cell-specific genes.

PMID- 16887830
TI  - Smad5 determines murine amnion fate through the control of bone morphogenetic
      protein expression and signalling levels.
AB  - Smad5 is an intracellular mediator of bone morphogenetic protein (Bmp)
      signalling. It is essential for primordial germ cell (PGC) development, for the
      development of the allantois and for amnion closure, as demonstrated by loss of
      Bmp signalling. By contrast, the appearance of ectopic PGC-like cells and
      regionalized ectopic vasculogenesis and haematopoiesis in thickened Smad5(m1/m1)
      amnion are amnion defects that have not been associated with loss of Bmp
      signalling components. We show that defects in amnion and allantois can already
      be detected at embryonic day (E) 7.5 in Smad5 mutant mice. However, ectopic Oct4
      positive (Oct4(+)) and alkaline phosphatase-positive (AP(+)) cells appear
      suddenly in thickened amnion at E8.5, and at a remote distance from the allantois
      and posterior primitive streak, suggesting a change of fate in situ. These
      ectopic Oct4(+), AP(+) cells appear to be Stella negative and hence cannot be
      called bona fide PGCs. We demonstrate a robust upregulation of Bmp2 and Bmp4
      expression, as well as of Erk and Smad activity, in the Smad5 mutant amnion. The
      ectopic expression of several Bmp target genes in different domains and the
      regionalized presence of cells of several Bmp-sensitive lineages in the mutant
      amnion suggest that different levels of Bmp signalling may determine cell fate.
      Injection of rBMP4 in the exocoelom of wild-type embryos can induce thickening of
      amnion, mimicking the early amnion phenotype in Smad5 mutants. These results
      support a model in which loss of Smad5 results paradoxically in gain of Bmp
      function defects in the amnion.

PMID- 16887831
TI  - The Drosophila caspase Ice is important for many apoptotic cell deaths and for
      spermatid individualization, a nonapoptotic process.
AB  - Caspase family proteases play important roles in the regulation of apoptotic cell
      death. Initiator caspases are activated in response to death stimuli, and they
      transduce and amplify these signals by cleaving and thereby activating effector
      caspases. In Drosophila, the initiator caspase Nc (previously Dronc) cleaves and
      activates two short-prodomain caspases, Dcp-1 and Ice (previously Drice),
      suggesting these as candidate effectors of Nc killing activity. dcp-1-null
      mutants are healthy and possess few defects in normally occurring cell death. To
      explore roles for Ice in cell death, we generated and characterized an Ice null
      mutant. Animals lacking Ice show a number of defects in cell death, including
      those that occur during embryonic development, as well as during formation of
      adult eyes, arista and wings. Ice mutants exhibit subtle defects in the
      destruction of larval tissues, and do not prevent destruction of salivary glands
      during metamorphosis. Cells from Ice animals are also markedly resistant to
      several stresses, including X-irradiation and inhibition of protein synthesis.
      Mutations in Ice also suppress cell death that is induced by expression of Rpr,
      Wrinkled (previously Hid) and Grim. These observations demonstrate that Ice plays
      an important non-redundant role as a cell death effector. Finally, we demonstrate
      that Ice participates in, but is not absolutely required for, the non-apoptotic
      process of spermatid differentiation.

PMID- 16887832
TI  - An unusual Zn-finger/FH2 domain protein controls a left/right asymmetric neuronal
      fate decision in C. elegans.
AB  - Gene regulatory networks that control the terminally differentiated state of a
      cell are, by and large, only superficially understood. In a mutant screen aimed
      at identifying regulators of gene batteries that define the differentiated state
      of two left/right asymmetric C. elegans gustatory neurons, ASEL and ASER, we have
      isolated a mutant, fozi-1, with a novel mixed-fate phenotype, characterized by de
      repression of ASEL fate in ASER. fozi-1 codes for a protein that functions in the
      nucleus of ASER to inhibit the expression of the LIM homeobox gene lim-6,
      neuropeptide-encoding genes and putative chemoreceptors of the GCY gene family.
      The FOZI-1 protein displays a highly unusual domain architecture, that combines
      two functionally essential C2H2 zinc-finger domains, which are probably involved
      in transcriptional regulation, with a formin homology 2 (FH2) domain, normally
      found only in cytosolic regulators of the actin cytoskeleton. We demonstrate that
      the FH2 domain of FOZI-1 has lost its actin polymerization function but maintains
      its phylogenetically ancient ability to homodimerize. fozi-1 genetically
      interacts with several transcription factors and micro RNAs in the context of
      specific regulatory network motifs. These network motifs endow the system with
      properties that provide insights into how cells adopt their stable terminally
      differentiated states.

PMID- 16887833
TI  - Cooperative activities of drosophila DE-cadherin and DN-cadherin regulate the
      cell motility process of ommatidial rotation.
AB  - Ommatidial rotation is a cell motility read-out of planar cell polarity (PCP)
      signaling in the Drosophila eye. Although the signaling aspects of PCP
      establishment are beginning to be unraveled, the mechanistic aspects of the
      associated ommatidial rotation process remain unknown. Here, we demonstrate that
      the Drosophila DE- and DN-cadherins have opposing effects on rotation. DE
      cadherin promotes rotation, as DE-cad mutant ommatidia rotate less than wild type
      or not at all. By contrast, the two DN-cadherins act to restrict this movement,
      with ommatidia rotating too fast in the mutants. The opposing effects of DE- and
      DN-cadherins result in a coordinated cellular movement, enabling ommatidia of the
      same stage to rotate simultaneously. Genetic interactions, phenotypic analysis
      and localization studies indicate that EGF-receptor and Frizzled-PCP signaling
      feed into the regulation of cadherin activity and localization in this context.
      Thus, DE- and DN-cadherins integrate inputs from at least two signaling pathways,
      resulting in a coordinated cell movement. A similar input into mammalian E- and N
      cadherins might function in the progression of diseases such as metastatic
      ovarian cancer.

PMID- 16887834
TI  - Rebuilding a health care system: war, reconstruction and health care reforms in
      Kosovo.
AB  - This article explores the complexity of a health care system reforms in a post
      conflict situation. It describes how the health care system was revamped
      immediately after the war, and then reorganized with Primary Health Care (PHC) as
      the fulcrum for change. It highlights the coordination problems, typical of a
      post-war situation when un-coordinated humanitarian assistance pours in. From the
      vantage points of Ministry of Health officials, the article details how the
      change process has gone over the years, the directions it has taken and the
      lessons learnt. It notes that reforms are often so fast that they outstrip the
      absorption capacity of the potential change agents because of their inadequate
      preparation for the new roles and responsibilities. This in turn threatens to
      undermine and weaken the very system that the reforms seek to strengthen. Several
      options adopted for change in Kosovo's health care system are at varying levels
      of implementation today. Some commentators have questioned if the policy for the
      new health care system has failed. We contend that there have been major
      organizational successes. But there are also shortcomings. There is also a
      potential danger that the health care system could partly revert to the old
      system. While some of the successes and shortcomings may be specific to Kosovo,
      many lessons learnt from Kosovo apply to health care reforms elsewhere.

PMID- 16887835
TI  - Comparison of routine care self-reported and biometrical data on hypertension and
      diabetes: results of the Utrecht Health Project.
AB  - BACKGROUND: Information on the prevalence of diseases is commonly gathered by
      questionnaires. Although the method is relatively inexpensive and efficient as
      opposed to physical examinations, the validity of the information collected is
      often questioned. The objective of this study was to assess the value of
      biometrical data complementary to self-reported questionnaire information for
      estimating the prevalence of hypertension and diabetes in the population at large
      and to examine factors that affect the accuracy of self-reporting. METHODS:
      Baseline data of 4950 adult participants of the Utrecht Health Project, a
      community-based prospective cohort study, were used to calculate sensitivity and
      specificity of self-reported hypertension and diabetes with the results of blood
      pressure measurements and blood glucose levels, corrected for current medication
      use, as the reference standard. Multivariate logistic regression analysis was
      performed to determine which participants' characteristics independently
      predicted the accuracy of self-reports. RESULTS: Overall sensitivity was 34.5%
      for self-reported data on hypertension and 58.9% for diabetes, while overall
      specificity was high for both conditions (96.4 and 99.4%, respectively). The
      agreement between self-reported and biometrical data was higher for diabetes than
      for hypertension and varied per subgroup. CONCLUSIONS: The use of self-reported
      data to estimate the prevalence of hypertension and diabetes may lead to
      underestimated prevalence estimates and biased associations with risk factors due
      to differential misclassification. Adding biometrical measurements to self
      reported questionnaire information will assure the validity of the data. The
      magnitude of the additional value of biometrical data depends on the condition
      studied and the characteristics of the population under investigation.

PMID- 16887836
TI  - Does a minimum-age law for purchasing tobacco make any difference? Swedish
      experiences over eight years.
AB  - BACKGROUND: The purpose was to study possible changes in adolescents'
      opportunities for purchasing tobacco during the period 1996-2005. The study also
      investigated regional differences in adolescents' opportunities for purchasing
      tobacco, and elucidated the efforts by the authorities to affect the compliance
      with the minimum-age law of 18. METHODS: In 1996, 1999, 2002, and 2005, 3150 test
      purchases of tobacco were conducted in controlled forms by 48 adolescents in
      three regions of Sweden. In addition, in 2005, 28 structured telephone interviews
      were conducted with key people in tobacco prevention work. RESULTS: In 1996, 84%
      of all test purchases in shops with a voluntary age-limit ended with the test
      purchasers succeeding in purchasing tobacco. This may be compared with 48% in
      2005, 8 years after the age-limit law was introduced. The result of the test
      purchases and of the interviews showed differences between the three regions in
      compliance and in activities connected with the minimum-age tobacco law.
      CONCLUSIONS: The study shows that the minimum-age law for the purchase of tobacco
      has had an effect on adolescents' opportunities for purchasing tobacco and that
      compliance has improved since its introduction in 1997. The result also indicates
      avenues for further improving compliance with the age-limit law.

PMID- 16887837
TI  - Early phase II study of uracil-tegafur plus doxorubicin in patients with
      unresectable advanced biliary tract cancer.
AB  - BACKGROUND: Standard chemotherapy for advanced biliary tract cancer has not been
      established. The purpose of this study was to evaluate the efficacy and toxicity
      of a combination chemotherapy of uracil-tegafur (UFT) and doxorubicin in patients
      with unresectable advanced biliary tract cancer. METHODS: Patients with
      histologically or cytologically confirmed, measurable biliary tract cancer,
      including intrahepatic or extrahepatic cholangiocarcinoma, gallbladder cancer and
      ampulla of Vater cancer, which was not amenable to surgery, were eligible for the
      study. Patients received oral UFT 300 mg/m(2) per day divided into two doses on
      Days 1-14 and intravenous doxorubicin 30 mg/m(2) on Day 1. This cycle was
      repeated every 21 days. Additional courses of this regimen were given until a
      maximum of 15 courses, disease progression or the appearance of unacceptable
      toxicity. RESULTS: Twenty-four patients from five institutions were enrolled
      between March 2004 and November 2004. Of the 24 patients, three had partial
      responses for an objective response rate of 12.5% (95% confidence interval, 2.7
      32.4%), 13 patients had stable disease, 7 had progressive disease and the final
      patient was not evaluated. Grade 3 toxicity was observed in 5 of the 24 patients
      (20.8%), and these toxicities included anorexia, fatigue, anemia and neutropenia.
      None had grade 4 toxicity. The median progression-free and overall survival time
      was 2.5 and 7.6 months, respectively. CONCLUSIONS: Combination chemotherapy of
      UFT and doxorubicin was well tolerated and showed preliminary moderate activity
      against advanced biliary tract cancer. Further investigation in a late phase II
      study involving a large number of patients is recommended.

PMID- 16887838
TI  - Surgery for dedifferentiated liposarcoma, presenting two radiologically and
      pathologically distinctive patterns.
AB  - In this paper, we report three cases with dedifferentiated liposarcoma in the
      lower extremities, presenting two patterns that are distinctively different
      radiologically and pathologically. The first case was a 67-year-old male who had
      discovered a mass in his left thigh, which was shown as a low and iso density
      mass between the muscles on computed tomography (CT). The second case was a 61
      year-old male who had suffered from an intramuscular tumor with a non-fatty
      sarcomatous area within the fatty components as shown on magenetic resonance
      imaging (MRI). The third case was a 52-year-old female who had presented with an
      intramuscular tumor of the left thigh, consisting of a mass with fat and another
      soft tissue tumor adjacent to the lipomatous component as detected with CT and
      MRI. The final pathological diagnoses of the resected specimens in all three
      cases were concluded to be dedifferentiated liposarcoma, composed of well
      differentiated liposarcomas and spindle and/or pleomorphic sarcomas, compatible
      with malignant fibrous histiocytoma. In all three cases, wide resection of the
      tumor was successfully carried out, and all patients have been continuously
      disease-free up to the most recent follow-up. Evaluation of the surgical margins
      for the resected specimens indicated that the safety margin for a
      dedifferentiated lesion should be accomplished as an adequate margin or more, and
      a marginal margin or more could be considered as safe only for the confined part
      of a well-differentiated liposarcoma.

PMID- 16887839
TI  - Early effect of surgery on quality of life in women with operable breast cancer.
AB  - BACKGROUND: Quality of life (QOL) after a diagnosis of breast cancer varies
      considerably across individuals. The treatment modality of the patients
      significantly contributes to their QOL. The present study reports the initial
      findings on the early effects of surgery in patients with breast cancer. METHODS:
      Two hundred and fifty-one women with breast cancer undergoing surgery were
      interviewed prior to and after the surgery using the Functional Assessment of
      Cancer Therapy for Breast (FACT-B). Trial Outcome Index (TOI) was calculated
      besides total and subscale scores. The results were analyzed using paired t-test
      and two-sample paired Wilcoxon signed rank test. Multivariate analysis was
      carried out using repeated measures general liner model with 2-way interactions.
      RESULTS: Significant reduction in physical well-being (P = 0.001), functional
      well-being (P = 0.00) and the breast-specific subscale (P = 0.000) was observed
      after surgery. No significant change was observed in social or emotional well
      being. Total FACT scores and TOI too showed significant declines (P = 0.000; and
      P = 0.000 respectively) on univariate analysis. Multivariate analysis, however,
      showed no difference in QOL after surgery, but QOL was significantly poor among
      women undergoing mastectomy. CONCLUSIONS: Results of the present study indicate
      no significant change in overall QOL immediately after the surgery, probably
      reflecting strong family and social support for these women. QOL was
      significantly better among women undergoing breast conservation compared with
      mastectomy.

PMID- 16887840
TI  - A case of acinar cell adenocarcinoma in the pancreatic tail.

PMID- 16887841
TI  - International comparisons of cumulative risk of uterine cancer, from cancer
      incidence in five continents Vol. VIII.

PMID- 16887842
TI  - Characterization of cyanobacteriochrome TePixJ from a thermophilic cyanobacterium
      Thermosynechococcus elongatus strain BP-1.
AB  - A putative photoreceptor gene, TepixJ, of a thermophilic cyanobacterium is
      homologous to SypixJ1 that mediates positive phototaxis in the unicellular motile
      cyanobacterium Synechocystis sp. PCC 6803. The putative chromophore-binding GAF
      domain of TePixJ protein was overexpressed as a fusion with a polyhistidine tag
      (His-TePixJ_GAF) in Synechocystis cells and isolated to homogeneity. The
      photoreversible conversion of His-TePixJ_GAF showed peaks at 531, 341 and 266 nm
      for the green light-absorbing form (Pg form), and peaks at 433 and 287 nm for the
      blue light-absorbing form (Pb form). At 77K, the Pg form fluoresced at 580 nm,
      while the Pb form did not emit any fluorescence. Mass spectrometry of the tryptic
      chromopeptide demonstrated that a phycocyanobilin isomer binds to the conserved
      cysteine at ring A via a thioether bond. It is established that TePixJ and
      SyPixJ1 are novel photoreceptors in cyanobacteria ('cyanobacteriochromes') that
      are similar, but distinct from the phytochromes and bacteriophytochromes.

PMID- 16887843
TI  - The poplar glycosyltransferase GT47C is functionally conserved with Arabidopsis
      Fragile fiber8.
AB  - Xylan is the major hemicellulose in dicot wood. Unraveling genes involved in the
      biosynthesis of xylan will be of importance in understanding the process of wood
      formation. In this report, we investigated the possible role of poplar GT47C, a
      glycosyltransferase belonging to family GT47, in the biosynthesis of xylan.
      PoGT47C from the hybrid poplar Populus alba x tremula exhibits 84% sequence
      similarity to Fragile fiber8 (FRA8), which is involved in the biosynthesis of
      glucuronoxylan in Arabidopsis. Phylogenetic analysis of glycosyltransferase
      family GT47 in the Populus trichocarpa genome revealed that GT47C is the only
      close homolog of FRA8. In situ hybridization showed that the PoGT47C gene was
      expressed in developing primary xylem, secondary xylem and phloem fibers of
      stems, and in developing secondary xylem of roots. Sequence analysis suggests
      that PoGT47C is a type II membrane protein, and study of the subcellular
      localization demonstrated that fluorescent protein-tagged PoGT47C was located in
      the Golgi. Immunolocalization with a xylan monoclonal antibody LM10 revealed a
      nearly complete loss of xylan signals in the secondary walls of fibers and
      vessels in the Arabidopsis fra8 mutant. Expression of PoGT47C in the fra8 mutant
      restored the secondary wall thickness and xylan content to the wild-type level.
      Together, these results suggest that PoGT47C is functionally conserved with FRA8
      and it is probably involved in xylan synthesis during wood formation.

PMID- 16887844
TI  - The female-specific Cs-ACS1G gene of cucumber. A case of gene duplication and
      recombination between the non-sex-specific 1-aminocyclopropane-1-carboxylate
      synthase gene and a branched-chain amino acid transaminase gene.
AB  - Cucumber (Cucumis sativus L.) is a monoecious plant in which female sex
      expression (gynoecy) is controlled by the Female (F) locus that can be modified
      by other sex-determining genes as well as by environmental and hormonal factors.
      As in many other cucurbits, ethylene is the major plant hormone regulating female
      sex expression. Previously we isolated the Cs-ACS1 (ACS, 1-aminocyclopropane-1
      carboxylate synthase) gene that encodes the rate-limiting enzyme in the ethylene
      biosynthetic pathway. We proposed that Cs-ACS1 is present in a single copy in
      monoecious (ffMM) plants whereas gynoecious plants (FFMM) contain an additional
      copy Cs-ACS1G that was mapped to the F locus. To study the origin of Cs-ACS1G, we
      cloned and analyzed both the gynoecious-specific Cs-ACS1G gene and the non-sex
      specific Cs-ACS1 gene. Our results indicate that Cs-ACS1G is the result of a
      relatively recent gene duplication and recombination, between Cs-ACS1 and a
      branched-chain amino acid transaminase (BCAT) gene. Taking into consideration
      that the Cs-ACS1G gene was mapped to the F locus, we propose that this
      duplication event gave rise to the F locus and to gynoecious cucumber plants.
      Computer analysis of the 1 kb region upstream of the transcription initiation
      site revealed several putative cis-acting regulatory elements that can
      potentially confer the responsiveness of Cs-ACS1G to developmental and hormonal
      factors and thereby control female sex determination in cucumber. These findings
      lead us to a model explaining the action of Cs-ACS1 and Cs-ACS1G in cucumber
      floral sex determination.

PMID- 16887845
TI  - Wegener's granulomatosis--probing the untold past of the man behind the eponym.

PMID- 16887846
TI  - Rheumatology in China--brief introduction of the development of Chinese
      rheumatology.

PMID- 16887848
TI  - Cervical cancer with pyometra--an insidious cause of uraemia in a post-menopausal
      woman.

PMID- 16887847
TI  - Visceral leishmaniasis infection in a rheumatoid arthritis patient treated with
      adalimumab.

PMID- 16887849
TI  - Screening for early chronic kidney disease--what method fits best?

PMID- 16887850
TI  - Renal fibrosis and the origin of the renal fibroblast.

PMID- 16887852
TI  - Xenotransplantation--will tolerance be essential?

PMID- 16887851
TI  - Anti-neutrophil cytoplasmic antibody (ANCA)-associated microscopic polyangiitis
      following a suppurative wound infection.

PMID- 16887853
TI  - Mathematical modelling of the course of chronic renal failure.

PMID- 16887854
TI  - Benefits of achieving the NCEP optional LDL-C goal among elderly patients with
      ACS.
AB  - AIMS: To assess the efficacy and safety of the achievement of the NCEP goal of
      LDL-C <1.8 mmol/L in elderly patients with ACS. METHODS AND RESULTS: The
      relationship between LDL-C at 30 days after ACS and subsequent clinical outcomes
      were compared among elderly patients (aged > or =70 years) vs. younger
      counterparts in the PROVE IT-TIMI 22 trial, using the composite endpoint of
      death, myocardial infarction, or unstable angina. Among 634 elderly patients, the
      achievement of the NCEP goal was associated with an 8% absolute and a 40%
      relative lower risk of events [Hazard ratio (HR) 0.60, 95% confidence interval
      (CI) 0.41-0.87, P = 0.008] vs. corresponding benefits of 2.3 and 26% in 3150
      younger patients (HR 0.74, 95% CI 0.59-0.94, P = 0.013). The estimated number of
      events preventable among the elderly by the achievement of these goals was 80
      events at 2 years for every 1000 patients at goal vs. those not at goal, compared
      with 23 events potentially prevented in younger patients. The incidence of major
      side effects among the elderly was similar to that in younger patients and did
      not differ with the intensity of the statin regimen. CONCLUSION: Among elderly
      ACS patients, achieving the new NCEP LDL-C optional goal as part of a secondary
      prevention strategy can be both as safe and effective as in younger patients.

PMID- 16887856
TI  - Deoxyribonuclease I: exploring the hidden side of myocardial infarction.

PMID- 16887857
TI  - The cost of implantable defibrillators: perceptions and reality.
AB  - AIMS: Recent guidelines have recommended more wide-ranging indications for the
      use of implantable cardioverter defibrillator (ICD) therapy, yet even more
      restrained previous guidelines have not been implemented for a variety of
      reasons. METHODS AND RESULTS: This brief review critically examines the reasons
      most frequently put forward to explain this failure. Contrary to the frequently
      repeated speculation that the risk stratification for sudden death and hence
      prophylactic placement of ICDs is reasonably accurate, there is little cost
      difference between pharmacotherapy and ICD treatment over the long term. ICD
      therapy does not utilize an undue proportion of the healthcare budget, and the
      healthcare systems in Europe can afford this therapy. CONCLUSION: Financial
      reasons are neither accurate nor adequate explanations for the failure of the
      European medical community to implement European guidelines for the implantation
      of ICDs for primary and secondary prevention of sudden cardiac death.

PMID- 16887858
TI  - Pride, prejudice, and paediatrics (women paediatricians in England before 1950).
AB  - Within the literature of the Enlightenment there are voices that called for the
      emancipation of women, and so began a--still unfinished--struggle for equality at
      home and in society. The campaign for women to enter the professions started in
      the 19th century. Women who wished to qualify and work as doctors faced what must
      have seemed to those of lesser courage and ability, to be insurmountable
      resistance. The early women doctors of the 19th century who were forced to obtain
      their training on the continent--in Zurich, Bern, and Paris--were part of a
      political movement and transatlantic network concerned with issues of women's
      rights, universal suffrage, women's health and public health measures. These
      women who "stormed the citadel" wanted to, and did, change society as well as
      medicine. Opposition to women's entry into medicine was led by doctors who
      defended the male monopoly against the threat to their prestige and purse. They
      argued that a woman's place was in the home as a wife and mother. Women's bodies,
      intellect, and temperament were not up to the demands of studying medicine, let
      alone practising as doctors. These arguments did not stop, but echoed down the
      20th century long after women had gained the right to qualify in medicine.

PMID- 16887859
TI  - Breast feeding and resilience against psychosocial stress.
AB  - BACKGROUND: Some early life exposures may result in a well controlled stress
      response, which can reduce stress related anxiety. Breast feeding may be a marker
      of some relevant exposures. AIMS: To assess whether breast feeding is associated
      with modification of the relation between parental divorce and anxiety. METHODS:
      Observational study using longitudinal birth cohort data. Linear regression was
      used to assess whether breast feeding modifies the association of parental
      divorce/separation with anxiety using stratification and interaction testing.
      Data were obtained from the 1970 British Cohort Study, which is following the
      lives of those born in one week in 1970 and living in Great Britain. This study
      uses information collected at birth and at ages 5 and 10 years for 8958 subjects.
      Class teachers answered a question on anxiety among 10 year olds using an
      analogue scale (range 0-50) that was log transformed to minimise skewness.
      RESULTS: Among 5672 non-breast fed subjects, parental divorce/separation was
      associated with a statistically significantly raised risk of anxiety, with a
      regression coefficient (95% CI) of 9.4 (6.1 to 12.8). Among the breast fed group
      this association was much lower: 2.2 (-2.6 to 7.0). Interaction testing confirmed
      statistically significant effect modification by breast feeding, independent of
      simultaneous adjustment for multiple potential confounding factors, producing an
      interaction coefficient of -7.0 (-12.8 to -1.2), indicating a 7% reduction in
      anxiety after adjustment. CONCLUSIONS: Breast feeding is associated with
      resilience against the psychosocial stress linked with parental
      divorce/separation. This could be because breast feeding is a marker of exposures
      related to maternal characteristics and parent-child interaction.

PMID- 16887860
TI  - Auditory integration training and other sound therapies for autism spectrum
      disorders: a systematic review.
AB  - OBJECTIVES: To determine the effectiveness of auditory integration training (AIT)
      or other methods of sound therapy in people with autism spectrum disorders (ASD).
      STUDY DESIGN: A systematic review was carried out of randomised controlled trials
      (RCTs) of adults or children with ASD. Meta-analysis was attempted. RESULTS: Six
      RCTs of AIT, including one crossover trial, were identified, with a total of 171
      participants aged 3-39 years. 17 different outcome measures were used, with only
      two outcome measures used by three or more studies. Meta-analysis was not
      possible owing to very high heterogeneity or presentation of data in unusable
      forms. Three studies did not show any benefit of AIT over control conditions.
      Three studies reported improvements at 3 months in the AIT group for total mean
      scores of the Aberrant Behaviour Checklist (ABC), which is of questionable
      validity. Of these, one study also reported improvements at 3 months in the AIT
      group for ABC subgroup scores. No significant adverse effects of AIT were
      reported. CONCLUSION: At present there is not sufficient evidence to support its
      use.

PMID- 16887861
TI  - The changing clinical presentation of coeliac disease.
AB  - BACKGROUND: There has been a growing recognition that coeliac disease is much
      more common than previously recognised, and this has coincided with the
      increasingly widespread use of serological testing. AIM: To determine whether the
      age at presentation and the clinical presentation of coeliac disease have changed
      with the advent of serological testing. METHODS: A 21-year review of
      prospectively recorded data on the mode of presentation of biopsy confirmed
      coeliac disease in a single regional centre. Presenting features over the past 5
      years were compared with those of the previous 16 years. Between 1983 and 1989
      (inclusive), no serological testing was undertaken; between 1990 and 1998,
      antigliadin antibody was used with occasional use of antiendomysial antibody and
      antireticulin antibody. From 1999 onwards, anti-tissue transglutaminase was used.
      RESULTS: 86 patients were diagnosed over the 21-year period: 50 children between
      1999 and 2004 compared with 25 children between 1990 and 1998 and 11 children
      between 1983 and 1989. The median age at presentation has risen over the years.
      Gastrointestinal manifestations as presenting features have decreased
      dramatically. In the past 5 years, almost one in four children with coeliac
      disease was diagnosed by targeted screening. CONCLUSION: This study reports
      considerable changes in the presentation of coeliac disease-namely, a decreased
      proportion presenting with gastrointestinal manifestations and a rise in the
      number of patients without symptoms picked up by targeted screening. Almost one
      in four children with coeliac disease is now diagnosed by targeted screening.
      Most children with coeliac disease remain undiagnosed. Paediatricians and primary
      care physicians should keep the possibility of coeliac disease in mind and have a
      low threshold for testing, so that the potential long-term problems associated
      with untreated coeliac disease can be prevented.

PMID- 16887862
TI  - The rate of NSAID-induced endoscopic ulcers increases linearly but not
      exponentially with age: a pooled analysis of 12 randomised trials.
AB  - The risk of major ulcer complications on treatment with non-steroidal anti
      inflammatory drugs (NSAIDs) is known to increase exponentially with age. However,
      in a pooled analysis of 12 trial arms, the incidence of endoscopic ulcers on
      treatment with NSAID was found to increase with age in a roughly linear fashion.
      Thus, it is concluded that increasing age is associated with both more frequent
      and more serious NSAID gastropathy.

PMID- 16887863
TI  - Smoking interacts with genetic risk factors in the development of rheumatoid
      arthritis among older Caucasian women.
AB  - OBJECTIVE: To determine whether the impact of tobacco exposure on rheumatoid
      arthritis (RA) risk is influenced by polymorphisms at the HLA-DRB1 and
      glutathione S-transferase M1 (GSTM1) loci. METHODS: Subjects were participants
      from a case-control study nested within the Iowa Women's Health Study, a
      population based, prospective cohort study of postmenopausal women. Incident RA
      cases (n = 115) were identified and medical records reviewed to confirm RA
      diagnosis. Controls without RA (n = 466) were matched with RA cases by age and
      ethnic background. HLA-DRB1 typing classified subjects according to the presence
      of alleles encoding the RA "shared epitope" (SE) sequence. GSTM1 was genotyped
      using a multiplex polymerase chain reaction assay. Conditional logistic
      regression was used to estimate the odds ratios (ORs) and 95% confidence
      intervals. RESULTS: Strong positive associations of smoking (OR = 6.0, p =
      0.004), SE positivity (OR = 4.6, p = 0.0006), and GSTM1 null genotype (OR = 3.4,
      p = 0.007) with risk of RA, and significant gene-environment interactions
      (smoking by SE interaction p = 0.034; smoking by GSTM1 interaction p = 0.047)
      were observed. Stratified analyses indicated that exposure to tobacco smoke
      primarily increased the risk of RA among subjects who lacked genetic risk factors
      for the disease (that is, SE negative or GSTM1 present). CONCLUSIONS: Although
      these findings require confirmation in other groups, the results support the
      importance of considering both genetic and environmental factors, and also their
      interaction, in studies of complex diseases like RA.

PMID- 16887864
TI  - Deoxycholate induces mitochondrial oxidative stress and activates NF-kappaB
      through multiple mechanisms in HCT-116 colon epithelial cells.
AB  - Nuclear factor kappa B (NF-kappaB) is a redox-associated transcription factor
      that is involved in the activation of survival pathways. We have previously shown
      that deoxycholate (DOC) activates NF-kappaB in hepatocytes and colon epithelial
      cells and that persistent exposure of HCT-116 cells to increasing concentrations
      of DOC results in the constitutive activation of NF-kappaB, which is associated
      with the development of apoptosis resistance. The mechanisms by which DOC
      activates NF-kappaB in colon epithelial cells, and whether natural antioxidants
      can reduce DOC-induced NF-kappaB activation, however, are not known. Also, it is
      not known if DOC can generate reactive oxygen species within mitochondria as a
      possible pathway of stress-related NF-kappaB activation. Since we have previously
      shown that DOC activates the NF-kappaB stress-response pathway in HCT-116 cells,
      we used this cell line to further explore the mechanisms of NF-kappaB activation.
      We found that DOC induces mitochondrial oxidative stress and activates NF-kappaB
      in HCT-116 cells through multiple mechanisms involving NAD(P)H oxidase, Na+/K+
      ATPase, cytochrome P450, Ca++ and the terminal mitochondrial respiratory complex
      IV. DOC-induced NF-kappaB activation was significantly (P < 0.05) inhibited by
      pre-treatment of cells with CAPE, EGCG, TMS, DPI, NaN3, EGTA, Ouabain and RuR.
      The NF-kappaB-activating pathways, induced by the dietary-related endogenous
      detergent DOC, provide mechanisms for promotion of colon cancer and identify
      possible new targets for chemoprevention.

PMID- 16887865
TI  - Sustained monomorphic ventricular tachycardia associated with unrepaired double
      chambered right ventricle.
AB  - Double-chambered right ventricle (DCRV) is a congenital anomaly characterized by
      the division of the ventricular cavity into two chambers separated by an abnormal
      hypertrophied muscular band or by severe hypertrophy of the muscle wall. Two
      adult patients with a diagnosis of DCRV presented sustained monomorphic
      ventricular tachycardia. In both cases, the clinical tachycardia was induced with
      programmed stimulation. After surgically resecting, the muscular band tachycardia
      could no longer be induced in the patient who underwent follow-up
      electrophysiological study. The outcome was favourable; there was no clinical
      recurrence of ventricular tachycardia in the two patients at 48 and 36 months,
      respectively.

PMID- 16887866
TI  - Right diaphragmatic paralysis following endocardial cryothermal ablation of
      inappropriate sinus tachycardia.
AB  - Inappropriate sinus tachycardia (IST) is a rare disorder amenable to catheter
      ablation when refractory to medical therapy. Radiofrequency (RF) catheter
      modification/ablation of the sinus node (SN) is the usual approach, although it
      can be complicated by right phrenic nerve paralysis. We describe a patient with
      IST, who had symptomatic recurrences despite previous acutely successful RF SN
      modifications, including the use of electroanatomical mapping/navigation system.
      We decided to try transvenous cryothermal modification of the SN. We used 2 min
      applications at -85 degrees C at sites of the earliest atrial activation guided
      by activation mapping during isoprenaline infusion. Every application was
      preceded by high output stimulation to reveal phrenic nerve proximity. During the
      last application, heart rate slowly and persistently fell below 85 bpm despite
      isoprenaline infusion, but right diaphragmatic paralysis developed. At 6 months
      follow-up, the patient was asymptomatic and the diaphragmatic paralysis had
      partially resolved. This is the first report, we believe, of successful SN
      modification for IST by endocardial cryoablation, although this case also
      demonstrates the considerable risk of right phrenic nerve paralysis even with
      this ablation energy.

PMID- 16887868
TI  - Negative flecainide test in Brugada syndrome patients with previous positive
      response.
AB  - Class I antiarrhythmic drug infusion has been established as the standard test to
      unmask Brugada syndrome. This report presents two patients with Brugada syndrome
      with positive flecainide response which was not reproducible in a subsequent
      test.

PMID- 16887867
TI  - Optimization of cardiac resynchronization guided by Doppler echocardiography:
      haemodynamic improvement and intraindividual variability with different pacing
      configurations and atrioventricular delays.
AB  - AIMS: Cardiac resynchronization therapy (CRT) improves symptoms in heart failure
      patients with intraventricular conduction delay (IVCD). Different pacing
      modalities produce variable activation patterns and are likely to result in
      different haemodynamic changes. The objective of this study was to demonstrate
      acute haemodynamic changes with different CRT configurations. METHODS AND
      RESULTS: In 26 patients (left ventricular ejection fraction 22.7+/-6.1%, QRS
      176+/-29 ms, New York Heart Association III/IV 18/8), a CRT device was implanted.
      An optimization procedure was performed including left (LVPEI) and right
      ventricular pre-ejection intervals, interventricular mechanical delay (IVD), left
      ventricular filling fraction (FTc), and myocardial performance index (MPI) during
      left and biventricular pacing with three different atrioventricular (AV) delays.
      An optimal mode and AV delay were defined. LVPEI changed from 166+/-27 to 139+/
      25 ms, IVD from 49+/-19 to 6+/-18 ms, MPI from 0.98+/-0.25 to 0.62+/-0.22, and
      FTc from 0.42+/-0.08 to 0.51+/-0.08 (P<0.001 for all comparisons). The
      variability was 39+/-20 ms for LVPEI, 55+/-24 ms for IVD, 0.11+/-0.07 for FTc,
      and 0.35+/-0.18 for MPI. CONCLUSION: Optimized resynchronization in heart failure
      patients with IVCD produces marked acute improvement of the altered cardiac cycle
      timing. The variability of Doppler parameters with different CRT modalities
      underlines the necessity of individualized settings and suggests that the
      patients' benefit may be jeopardized without optimization.

PMID- 16887869
TI  - The mammalian transcriptome and the cellular complexity of the brain.

PMID- 16887870
TI  - A spoonful of sugar helps the KV channel activity go down.

PMID- 16887871
TI  - AMPA type glutamate receptor mediates neurotransmission at turtle vestibular
      calyx synapse.
AB  - Glutamate is thought to be the main neurotransmitter at the synapse between the
      type I vestibular hair cell and its cognate calyx afferent. The present study was
      designed to identify the type of glutamate receptors involved in
      neurotransmission at this unusual synapse. Immunocytochemistry showed that AMPA
      GluR2, NMDA NR1 and NR2A/B subunits of the glutamate receptors were confined to
      the synaptic contact. We then examined the electrical activity at calyx terminals
      using direct electrophysiological recordings from intact dendritic terminals in
      explanted turtle posterior crista. We found that sodium-based action potentials
      support a background discharge that could be modulated by the mechanical
      stimulation of the hair bundle of the sensory cells. These activities were
      prevented by blocking both the mechano-electrical transduction channels and L
      type voltage-gated Ca(2+) channels involved in synaptic transmission. Although
      pharmacological analysis revealed that NMDA receptors could operate, our results
      show that AMPA receptors are mainly involved in synaptic neurotransmission. We
      conclude that although both AMPA and NMDA glutamate receptor subunits are present
      at the calyx synapse, only AMPA receptors appear to be involved in the synaptic
      transmission between the type I vestibular hair cell and the calyx afferent.

PMID- 16887872
TI  - 5-HT evokes sensory long-term facilitation of rodent carotid body via activation
      of NADPH oxidase.
AB  - 5-Hydroxytryptamine (5-HT) evokes long-term activation of neuronal activity in
      the nervous system. Carotid bodies, the sensory organs for detecting arterial
      oxygen, express 5-HT. In the present study we examined whether 5-HT evokes
      sensory long-term facilitation (LTF) of the carotid body, and if so by what
      mechanism(s). Experiments were performed on anaesthetized adult rats and mice.
      Sensory activity was recorded from carotid bodies ex vivo. Spaced (3 x 15 s of
      100 nm at 5 min intervals) but not mass (300 nm, 45 s) application of 5-HT
      elicited LTF, whereas both modes of 5-HT application evoked initial sensory
      excitation of the carotid bodies in rats. Ketanserin, a 5-HT(2) receptor
      antagonist prevented sensory LTF but not the initial sensory excitation. Spaced
      application of 5-HT activated protein kinase C (PKC) as evidenced by increased
      phosphorylations of PKC at Thr(514) and myristoylated alanine-rich C kinase
      substrate (MARCKS) and these effects were abolished by ketanserin as well as
      bisindolylmaleimide (Bis-1), an inhibitor of PKC. Bis-1 prevented 5-HT-evoked
      sensory LTF. 5-HT increased NADPH oxidase activity and PKC-dependent
      phosphorylation of p47(phox) subunit of the oxidase complex. NADPH oxidase
      inhibitors (apocynin and diphenyl iodinium), as well as an anti-oxidant (N-acetyl
      cysteine), prevented 5-HT-evoked sensory LTF. Mice deficient in gp91(phox), the
      membrane subunit of the NADPH oxidase complex, showed no sensory LTF, although
      responding to 5-HT with initial afferent nerve activation, whereas both LTF and
      initial excitation by 5-HT were seen in wild-type mice. These results demonstrate
      that spaced but not mass application of 5-HT elicits sensory LTF of the carotid
      body via activation of 5-HT(2) receptors, which involves a novel signalling
      mechanism coupled to PKC-dependent activation of NADPH oxidase.

PMID- 16887873
TI  - Ancillary subunits and stimulation frequency determine the potency of chromanol
      293B block of the KCNQ1 potassium channel.
AB  - KCNQ1 (Kv7.1 or KvLQT1) encodes the alpha-subunit of a voltage-gated potassium
      channel found in tissues including heart, brain, epithelia and smooth muscle.
      Tissue-specific characteristics of KCNQ1 current are diverse, due to modification
      by ancillary subunits. In heart, KCNQ1 associates with KCNE1 (MinK), producing a
      slowly activating voltage-dependent channel. In epithelia, KCNQ1 co-assembles
      with KCNE3 (Mirp2) producing a constitutively open channel. Chromanol 293B is a
      selective KCNQ1 blocker. We studied drug binding and frequency dependence of 293B
      on KCNQ1 and ancillary subunits expressed in Xenopus oocytes. Ancillary subunits
      altered 293B potency up to 100-fold (IC(50) for KCNQ1 = 65.4 +/- 1.7 microm;
      KCNQ1/KCNE1 = 15.1 +/- 3.3 microm; KCNQ1/KCNE3 = 0.54 +/- 0.18 microm). Block of
      KCNQ1 and KCNQ1/KCNE3 was time independent, but 293B altered KCNQ1/KCNE1
      activation. We therefore studied frequency-dependent block of KCNQ1/KCNE1.
      Repetitive rapid stimulation increased KCNQ1/KCNE1 current biphasically, and 293B
      abolished the slow component. KCNQ1/KCNE3[V72T] activates slowly with a
      KCNQ1/KCNE1-like phenotype, but retains the high affinity binding of KCNQ1/KCNE3,
      demonstrating that subunit-mediated changes in gating can be dissociated from
      subunit-mediated changes in affinity. This study demonstrates the KCNQ1
      pharmacology is significantly altered by ancillary subunits. The response of
      KCNQ1 to specific blockers will therefore be critically dependent on the
      electrical stimulation pattern of the target organ. Furthermore, the dissociation
      between gating and overall affinity suggests that mutations in ancillary subunits
      can potentially strongly alter drug sensitivity without obvious functional
      changes in gating behaviour, giving rise to unexpected side-effects such as a
      predisposition to acquired long QT syndrome.

PMID- 16887874
TI  - Active hair bundle movements in auditory hair cells.
AB  - The frequency selectivity of mammalian hearing depends on not only the passive
      mechanics of the basilar membrane but also an active amplification of the
      mechanical stimulus by the cochlear hair cells. The common view is that
      amplification stems from the somatic motility of the outer hair cells (OHCs),
      changes in their length impelled by voltage-dependent transitions in the membrane
      protein prestin. Whether this voltage-controlled mechanism, whose frequency range
      may be limited by the membrane time constant, has the band width to cover the
      entire auditory range of mammals is uncertain. However, there is ample evidence
      for an alternative mode of force generation by hair cells of non-mammals, such as
      frogs and turtles, which probably lack prestin. The latter process involves
      active motion of the hair bundle underpinned by conformational changes in the
      mechanotransducer (MT) channels and activation of one or more isoforms of myosin.
      This review summarizes evidence for active hair bundle motion and its connection
      to MT channel adaptation. Key factors for the hair bundle motor to play a role in
      the mammalian cochlea include the size and speed of force production.

PMID- 16887875
TI  - Differences between the scaling of miniature IPSCs and EPSCs recorded in the
      dendrites of CA1 mouse pyramidal neurons.
AB  - Anatomical studies have described inhibitory synaptic contacts on apical
      dendrites, and an abundant number of GABAergic synapses on the somata and
      proximal dendrites of CA1 pyramidal cells of the hippocampus. The number of
      inhibitory contacts decreases dramatically with distance from the soma, but the
      local electrophysiological characterization of these synapses at their site of
      origin in the dendrites is missing. We directly recorded dendritic GABA receptor
      mediated inhibitory synaptic events in adult mouse hippocampal CA1 pyramidal
      neurons and compared them to excitatory synaptic currents recorded at the same
      sites. Miniature GABAergic events were evoked using localized application of a
      hyperosmotic solution to the apical dendrites in the vicinity of the dendritic
      whole-cell recording pipette. Glutamatergic synaptic events were blocked by
      kynurenic acid, leaving picrotoxin-sensitive IPSCs. We measured the amplitude and
      kinetic properties of mIPSCs at the soma and at three different dendritic
      locations. The amplitude of mIPSCs recorded at the various sites was similar
      along the somato-dendritic axis. The rise- and decay-times of local mIPSCs were
      also independent of the location of the synapses. The frequency of mIPSCs was 5
      Hz at the soma, in contrast to < 0.5 Hz at dendritic sites, which could be
      increased to 10-20 Hz and 6-10 Hz, respectively, by our hyperosmotic stimulation
      protocol. Miniature glutamatergic events were evoked with the same protocol after
      blocking inhibitory synapses by bicucculine. The measured amplitudes increased
      along the somato-dendritic axis proportionally with their distance from the soma.
      The measured kinetic properties were independent of location. Consistent with the
      idea that IPSCs may have a restricted local effect in the dendrites, our data
      show a lack of distance-dependent scaling of miniature inhibitory synaptic
      events, in contrast to the scaling of excitatory events recorded at the same
      sites.

PMID- 16887876
TI  - Regulation of electromotility in the cochlear outer hair cell.
AB  - Mechanosensory outer hair cells play an essential role in the amplification of
      sound-induced vibrations within the mammalian cochlea due to their ability to
      contract or elongate following changes of the intracellular potential. This
      unique property of outer hair cells is known as electromotility. Selective
      efferent innervation of these cells within the organ of Corti suggests that
      regulation of outer hair cell electromotility may be the primary function of the
      efferent control in the cochlea. A number of studies demonstrate that outer hair
      cell electromotility is indeed modulated by the efferent neurotransmitter,
      acetylcholine. The effects of acetylcholine on outer hair cells include cell
      hyperpolarization and a decrease of the axial stiffness, both mediated by
      intracellular Ca(2+). This article reviews these results and considers other
      potential mechanisms that may regulate electromotility, such as direct
      modification of the plasma membrane molecular motors, alteration of intracellular
      pressure, and modification of intracellular chloride concentration.

PMID- 16887877
TI  - Spontaneous rhythmic field potentials of isolated mouse hippocampal-subicular
      entorhinal cortices in vitro.
AB  - The rodent hippocampal circuit is capable of exhibiting in vitro spontaneous
      rhythmic field potentials (SRFPs) of 1-4 Hz that originate from the CA3 area and
      spread to the CA1 area. These SRFPs are largely correlated with GABA-A IPSPs in
      pyramidal neurons and repetitive discharges in inhibitory interneurons. As such,
      their generation is thought to result from cooperative network activities
      involving both pyramidal neurons and GABAergic interneurons. Considering that the
      hippocampus, subiculum and entorhinal cortex function as an integrated system
      crucial for memory and cognition, it is of interest to know whether similar SRFPs
      occur in hippocampal output structures (that is, the subiculum and entorhinal
      cortex), and if so, to understand the cellular basis of these subicular and
      entorhinal SRFPs as well as their temporal relation to hippocampal SRFPs. We
      explored these issues in the present study using thick hippocampal-subicular
      entorhinal cortical slices prepared from adult mice. SRFPs were found to spread
      from the CA1 area to the subicular and entorhinal cortical areas. Subicular and
      entorhinal cortical SRFPs were correlated with mixed IPSPs/EPSPs in local
      pyramidal neurons, and their generation was dependent upon the activities of GABA
      A and AMPA glutamate receptors. In addition, the isolated subicular circuit could
      elicit SRFPs independent of CA3 inputs. We hypothesize that the SRFPs represent a
      basal oscillatory activity of the hippocampal-subicular-entorhinal cortices and
      that the subiculum functions as both a relay and an amplifier, spreading the
      SRFPs from the hippocampus to the entorhinal cortex.

PMID- 16887878
TI  - A novel site of synaptic relay for climbing fibre pathways relaying signals from
      the motor cortex to the cerebellar cortical C1 zone.
AB  - The climbing fibre projection from the motor cortex to the cerebellar cortical C1
      zone in the posterior lobe of the rat cerebellum was investigated using a
      combination of physiological, anatomical and neuropharmacological techniques.
      Electrical stimulation of the ipsilateral fore- or hindimbs or somatotopically
      corresponding parts of the contralateral motor cortex evoked climbing fibre field
      potentials at the same cerebellar recording sites. Forelimb-related responses
      were located in the C1 zone in the paramedian lobule or lobulus simplex and
      hindlimb-related responses were located in the C1 zone in the copula pyramidis.
      Microinjections of anterograde axonal tracer (Fluoro-Ruby or Fluoro-Emerald) were
      made into the fore- or hindlimb parts of the motor cortex where stimulation
      evoked the largest cerebellar responses. After a survival period of 7-10 days,
      the neuraxis was examined for anterograde labelling. No terminal labelling was
      ever found in the inferior olive, but labelled terminals were consistently found
      in a well-localized site in the dorso-medial medulla, ventral to the gracile
      nucleus, termed the matrix region. Pharmacological inactivation of the matrix
      region (2 mm caudal to the obex) selectively reduced transmission in descending
      (cerebro-olivocerebellar) but not ascending (spino-olivocerebellar) paths
      targeting fore- or hindlimb-receiving parts of the C1 zone. Transmission in spino
      olivocerebellar paths was either unaffected, or in some cases increased. The
      identification of a novel pre-olivary relay in cerebro-olivocerebellar paths
      originating from fore- and hindlimb motor cortex has implications for the
      regulation of transmission in climbing fibre pathways during voluntary movements
      and motor learning.

PMID- 16887879
TI  - The N-terminal transmembrane domain (TMD0) and a cytosolic linker (L0) of
      sulphonylurea receptor define the unique intrinsic gating of KATP channels.
AB  - ATP-sensitive potassium (K(ATP)) channels comprise four pore-forming Kir6 and
      four regulatory sulphonylurea receptor (SUR) subunits. SUR, an ATP-binding
      cassette protein, associates with Kir6 through its N-terminal transmembrane
      domain (TMD0). TMD0 connects to the core domain of SUR through a cytosolic linker
      (L0). The intrinsic gating of Kir6.2 is greatly altered by SUR. It has been
      hypothesized that these changes are conferred by TMD0. Exploiting the fact that
      the pancreatic (SUR1/Kir6.2) and the cardiac (SUR2A/Kir6.2) K(ATP) channels show
      different gating behaviours, we have tested this hypothesis by comparing the
      intrinsic gating of Kir6.2 with the last 26 residues deleted (Kir6.2Delta26) co
      expressed with SUR1, S1-TMD0, SUR2A and S2-TMD0 at -40 and -100 mV (S is an
      abbreviation for SUR; TMD0/Kir6.2Delta26, but not TMD0/Kir6.2, can exit the
      endoplastic reticulum and reach the cell membrane). Single-channel kinetic
      analyses revealed that the mean burst and interburst durations are shorter for
      TMD0/Kir6.2Delta26 than for the corresponding SUR channels. No differences were
      found between the two TMD0 channels. We further demonstrated that in isolation
      even TMD0-L0 (SUR truncated after L0) cannot confer the wild-type intrinsic
      gating to Kir6.2Delta26 and that swapping L0 (SUR truncated after L0)between SUR1
      and SUR2A only partially exchanges their different intrinsic gating. Therefore,
      in addition to TMD0, L0 and the core domain also participate in determining the
      intrinsic gating of Kir6.2. However, TMD0 and L0 are responsible for the
      different gating patterns of full-length SUR1 and SUR2A channels. A kinetic model
      with one open and four closed states is presented to explain our results in a
      mechanistic context.

PMID- 16887881
TI  - Focus-on-form instructional methods promote deaf college students' improvement in
      English grammar.
AB  - Focus-on-form English teaching methods are designed to facilitate second-language
      learners' noticing of target language input, where "noticing" is an acquisitional
      prerequisite for the comprehension, processing, and eventual integration of new
      grammatical knowledge. While primarily designed for teaching hearing second
      language learners, many focus-on-form methods lend themselves to visual
      presentation. This article reports the results of classroom research on the
      visually based implementation of focus-on-form methods with deaf college students
      learning English. Two of 3 groups of deaf students received focus-on-form
      instruction during a 10-week remedial grammar course; a third control group
      received grammatical instruction that did not involve focus-on-form methods. The
      2 experimental groups exhibited significantly greater improvement in English
      grammatical knowledge relative to the control group. These results validate the
      efficacy of visually based focus-on-form English instruction for deaf students of
      English and set the stage for the continual search for innovative and effective
      English teaching methodologies.

PMID- 16887880
TI  - Sensory elements within the circular muscle are essential for mechanotransduction
      of ongoing peristaltic reflex activity in guinea-pig distal colon.
AB  - We have recently identified a population of mechanosensory myenteric S
      interneurons in the distal colon of guinea-pigs. However, the role of the
      longitudinal (LM) and circular muscle (CM) in transducing these mechanosensory
      signals into enteric reflexes is unclear. In this study, we have investigated
      whether the LM or CM layer is necessary for activation of ascending excitatory
      and descending inhibitory neuronal pathways by static stretch of the paralysed
      isolated guinea-pig distal colon. Simultaneous intracellular recordings were made
      from pairs of CM cells at either end of isolated sheet preparations of distal
      colon that were devoid of mucosa and submucous plexus; and were maintained under
      circumferential stretch. In the presence of nifedipine (1 microm), an ongoing
      discharge of excitatory junction potentials (EJPs) and inhibitory junction
      potentials (IJPs) were recorded simultaneously at the oral and anal ends of the
      preparation. When the LM was sharp dissected off the myenteric plexus, the
      synchronized discharge of ascending EJPs and descending IJPs in the CM layer was
      unaffected. In contrast, when the majority of CM was sharp dissected off the
      myenteric plexus, ongoing neural activity was absent, or substantially decreased
      in both the LM and CM. In these preparations, immunohistochemical staining,
      together with transmural electrical stimuli confirmed that the myenteric plexus
      was always present and intact in these preparations. When full-thickness strips
      of CM were removed from progressively longer lengths of myenteric plexus, a
      graded reduction in the correlation of coordinated oral EJPs and anal IJPs
      occurred. However, removing approximately 40% of the thickness of CM layer from
      the entire preparation did not significantly disrupt, nor reduce the degree of
      correlation between oral EJPs and anal IJPs, suggesting that critical sensory
      elements did not lie adjacent to the submucosal plexus. It is concluded that
      mechanosensory transmission that underlies repetitive firing of ascending
      excitatory and descending inhibitory neuronal pathways is critically dependent
      upon sensory elements within the CM layer. These elements are likely to activate
      stretch-sensitive interneurons in the myenteric plexus. No evidence was found to
      suggest that the connectivity between the LM and the myenteric plexus was
      required for mechanotransduction.

PMID- 16887882
TI  - Thyroid hormone transport by the human monocarboxylate transporter 8 and its rate
      limiting role in intracellular metabolism.
AB  - Cellular entry of thyroid hormone is mediated by plasma membrane transporters. We
      have identified rat monocarboxylate transporter 8 (MCT8) as an active and
      specific thyroid hormone transporter. The MCT8 gene is located on the X
      chromosome. The physiological relevance of MCT8 has been demonstrated by the
      identification of hemizygous mutations in this gene in males with severe
      psychomotor retardation and elevated serum T(3) levels. We have characterized
      human (h) MCT8 by analysis of iodothyronine uptake and metabolism in cell lines
      transiently transfected with hMCT8 cDNA alone or together with cDNA coding for
      iodothyronine deiodinase D1, D2, or D3. MCT8 mRNA was detected by RT-PCR in a
      number of human cell lines as well as in COS1 cells but was low to undetectable
      in other cell lines, including JEG3 cells. MCT8 protein was not detected in
      nontransfected cell lines tested by immunoblotting using a polyclonal C-terminal
      hMCT8 antibody but was detectable in transfected cells at the expected size (61
      kDa). Transfection of COS1 and JEG3 cells with hMCT8 cDNA resulted in 2- to 3
      fold increases in uptake of T(3) and T(4) but little or no increase in rT(3) or
      3,3'-diiodothyronine (3,3'-T(2)) uptake. MCT8 expression produced large increases
      in T(4) metabolism by cotransfected D2 or D3, T(3) metabolism by D3, rT(3)
      metabolism by D1 or D2, and 3,3'-T(2) metabolism by D3. Affinity labeling of
      hMCT8 protein was observed after incubation of intact transfected cells with N
      bromoacetyl-[(125)I]T(3). hMCT8 also facilitated affinity labeling of
      cotransfected D1 by bromoacetyl-T(3). Our findings indicate that hMCT8 mediates
      plasma membrane transport of iodothyronines, thus increasing their intracellular
      availability.

PMID- 16887883
TI  - Peroxisome proliferator-activated receptor-gamma activates p53 gene promoter
      binding to the nuclear factor-kappaB sequence in human MCF7 breast cancer cells.
AB  - The aim of the present study was to provide new mechanistic insight into the
      growth arrest and apoptosis elicited by peroxisome proliferator-activated
      receptor (PPAR)gamma in breast cancer cells. We ascertained that PPARgamma
      mediates the inhibition of cycle progression in MCF7 cells exerted by the
      specific PPARgamma agonist rosiglitazone [BRL4653 (BRL)], because this response
      was no longer notable in the presence of the receptor antagonist GW9662. We also
      provided evidence that BRL is able to up-regulate mRNA and protein levels of the
      tumor suppressor gene p53 and its effector p21(WAF1/Cip1) in a time- and dose
      dependent manner. Moreover, in transfection experiments with deletion mutants of
      the p53 gene promoter, we documented that the nuclear factor-kappaB sequence is
      required for the transcriptional response to BRL. Interestingly, EMSA showed that
      PPARgamma binds directly to the nuclear factor-kappaB site located in the
      promoter region of p53, and chromatin immunoprecipitation experiments
      demonstrated that BRL increases the recruitment of PPARgamma on the p53 promoter
      sequence. Next, both PPARgamma and p53 were involved in the cleavage of caspases
      9 and DNA fragmentation induced by BRL, given that GW9662 and an expression
      vector for p53 antisense blunted these effects. Our findings provide evidence
      that the PPARgamma agonist BRL promotes the growth arrest and apoptosis in MCF7
      cells, at least in part, through a cross talk between p53 and PPARgamma, which
      may be considered an additional target for novel therapeutic interventions in
      breast cancer patients.

PMID- 16887884
TI  - In vivo induction of glial cell proliferation and axonal outgrowth and
      myelination by brain-derived neurotrophic factor.
AB  - Brain-derived neurotrophic factor (BDNF) belongs to the neurotrophin family of
      neuronal cell survival and differentiation factors but is thought to be involved
      in neuronal cell proliferation and myelination as well. To explore the role of
      BDNF in vivo, we employed the intermediate pituitary melanotrope cells of the
      amphibian Xenopus laevis as a model system. These cells mediate background
      adaptation of the animal by producing high levels of the prohormone
      proopiomelanocortin (POMC) when the animal is black adapted. We used stable X.
      transgenesis in combination with the POMC gene promoter to generate transgenic
      frogs overexpressing BDNF specifically and physiologically inducible in the
      melanotrope cells. Intriguingly, an approximately 25-fold overexpression of BDNF
      resulted in hyperplastic glial cells and myelinated axons infiltrating the
      pituitary, whereby the transgenic melanotrope cells became located dispersed
      among the induced tissue. The infiltrating glial cells and axons originated from
      both peripheral and central nervous system sources. The formation of the
      phenotype started around tadpole stage 50 and was induced by placing white
      adapted transgenics on a black background, i.e. after activation of transgene
      expression. The severity of the phenotype depended on the level of transgene
      expression, because the intermediate pituitaries from transgenic animals raised
      on a white background or from transgenics with only an approximately 5-fold BDNF
      overexpression were essentially not affected. In conclusion, we show in a
      physiological context that, besides its classical role as neuronal cell survival
      and differentiation factor, in vivo BDNF can also induce glial cell proliferation
      as well as axonal outgrowth and myelination.

PMID- 16887885
TI  - A novel pathway involving progesterone receptor, endothelin-2, and endothelin
      receptor B controls ovulation in mice.
AB  - The steroid hormone progesterone (P) plays a pivotal role during ovulation. Mice
      lacking P receptor (Pgr) gene fail to ovulate due to a defect in follicular
      rupture. The P receptor (PGR)-regulated pathways that modulate ovulation,
      however, remain poorly understood. To identify these pathways, we performed gene
      expression profiling using ovaries from mice subjected to gonadotropin-induced
      superovulation in the presence and in the absence of CDB-2914, a synthetic PGR
      antagonist. Prominent among the genes that were down-regulated in response to CDB
      2914 was endothelin (ET)-2, a potent vasoactive molecule. ET-2 mRNA was
      transiently induced in mural granulosa cells of the preovulatory follicles
      immediately preceding ovulation. This induction was absent in the ovaries of PGR
      null mice, indicating a critical role of this receptor in ET-2 expression. To
      investigate the functional role of ET-2 during ovulation, we employed selective
      antagonists of endothelin receptors, ETR-A and ETR-B. Mice treated with an ETR-B
      antagonist exhibited a dramatic (>85%) decline in the number of released oocytes.
      Strong expression of ETR-B was observed in the mural and cumulus granulosa cells
      of the preovulatory follicles as well as in the capillaries lining the inner
      border of the theca interna. We also identified cGMP-dependent protein kinase II,
      a previously reported PGR-regulated gene, as a downstream target of ET-2 during
      ovulation. Collectively, our studies uncovered a unique pathway in which ET-2,
      produced by PGR in mural granulosa cells, acts in a paracrine or autocrine manner
      on multiple cell types within the preovulatory follicle to control the final
      events leading to its rupture.

PMID- 16887886
TI  - Selective modulation of protein kinase A I and II reveals distinct roles in
      thyroid cell gene expression and growth.
AB  - A global gene expression profiling of TSH stimulation on differentiated (FRTL5)
      and partially dedifferentiated [FRT/TSHR (TSH receptor)] rat thyroid cells was
      performed. A total of 123 TSH-regulated genes (95 newly described) were
      identified in FRTL5, whereas no significant transcriptional modifications were
      seen in FRT/TSHR cells. Because regulatory subunit IIbeta (RIIbeta) of protein
      kinase A (PKA), a key element downstream of cAMP, was expressed in FRTL5 but not
      in cAMP-refractory FRT/TSHR cells, we hypothesized that this gene may play an
      important role in TSH signaling. We therefore performed a series of experiments
      to investigate the involvement of RIIbeta and the different PKA isoforms. A
      positive effect of PKA II- but not of PKA I-selective activation on gene
      transcription and proliferation in FRTL5 cells, as well as an impairment of TSH
      nuclear effects after RIIbeta silencing were observed, suggesting that PKA II
      plays an essential role in TSH signaling. This view was supported by the
      restoration of TSH nuclear effects after reexpression of RIIbeta in FRT/TSHR
      cells. Because PKA I stimulation could increase iodide uptake in FRTL5 cells
      without affecting gene transcription, PKA I may mediate TSH actions at
      posttranscriptional levels. Analyses on three human cancer cell lines confirmed
      the possible loss of RIIbeta expression and antiproliferative activity of PKA I
      selective cAMP analogs ( approximately 60% at 200 microm in BRAF-mutated cells).
      The inhibitory effect of PKA I apparently required constitutive MAPK activation
      and was associated with an inhibition of ERK phosphorylation. These findings may
      open new therapeutic perspectives in patients with thyroid cancer.

PMID- 16887887
TI  - A phosphorylation cluster of five serine and threonine residues in the C-terminus
      of the follicle-stimulating hormone receptor is important for desensitization but
      not for beta-arrestin-mediated ERK activation.
AB  - Classically, the FSH receptor (FSH-R) mediates its effects through coupling to
      guanine nucleotide-binding protein alpha S subunit (Galpha(s)) and activation of
      the cAMP/protein kinase A (PKA) signaling pathway. beta-Arrestins are rapidly
      recruited to the FSH-activated receptor and play key roles in its desensitization
      and internalization. Here, we show that the FSH-R expressed in HEK 293 cells
      activated ERK by two temporally distinct pathways dependent, respectively, on
      Galpha(s)/PKA and beta-arrestins. Galpha(s)/PKA-dependent ERK activation was
      rapid, transient, and blocked by H89 (a PKA inhibitor), but it was insensitive to
      small interfering RNA-mediated depletion of beta-arrestins. beta-Arrestin
      dependent ERK activation was slower but more sustained and was insensitive to
      H89. We identified five Ser/Thr residues in the C terminus of the receptor (638
      644) as a major phosphorylation site. Mutation of these residues into Ala (5A FSH
      R) significantly reduced the stability of FSH-induced beta-arrestin 1 and 2
      interaction when compared with the wild-type receptor. As expected, the 5A FSH-R
      mediated cAMP accumulation was enhanced, and its internalization was reduced. In
      striking contrast, the ability of the 5A FSH-R to activate ERK via the beta
      arrestin-dependent pathway was increased. G protein-coupled receptor kinase 5
      (GRK5) and GRK6 were required for beta-arrestin-dependent ERK activation by both
      the wild-type and 5A FSH-R. By contrast, GRK2 depletion enhanced ERK activation
      by the wild-type FSH-R but not by the 5A FSH-R. In conclusion, we demonstrate the
      existence of a beta-arrestin-dependent, GRK-regulated mechanism for ERK
      activation by the FSH-R. A phosphorylation cluster in the C terminus of the FSH
      R, identified as a site of beta-arrestin recruitment, positively regulated both
      desensitization and internalization but negatively regulated beta-arrestin
      dependent ERK activation.

PMID- 16887888
TI  - Violence exposure and burn-out among Turkish nursing home staff.
AB  - AIM: The aim of this study was to describe the frequency of violence against
      personnel from residents and to identify the prevalence of burn-out among staff
      working in nursing homes. METHODS: The study was performed in two cities in the
      west of Turkey. A semi-structured questionnaire on violence and Pines' Burnout
      scale were distributed among all the staff working in six nursing homes, and 214
      of them responded. RESULTS: Of the total number of respondents, 56% stated that
      they had been exposed to violence during the preceding year. More than 20% stated
      that they had reported violence to their supervisor. Less than 10% had received
      medical or psychological support following the event. Violent incidents were
      reported significantly more frequently among staff who reported problems working
      with elderly residents. There was no relationship between violence towards staff
      and burn-out. CONCLUSIONS: Violence is commonly experienced by care workers in
      nursing homes for the elderly. Strategies to improve occupational conditions in
      nursing homes are required.

PMID- 16887889
TI  - Medication adherence in schizophrenia: exploring patients', carers' and
      professionals' views.
AB  - One of the major clinical problems in the treatment of people with schizophrenia
      is suboptimal medication adherence. Most research focusing on determinants of
      nonadherence use quantitative research methods. These studies have some important
      limitations in exploring the decision-making process of patients concerning
      medication. In this study we explore factors influencing medication adherence
      behavior in people with schizophrenia using concept mapping. Concept mapping is a
      structured qualitative method and was performed in 4 European countries.
      Participants were 27 patients with schizophrenia, 29 carers, and 28 professionals
      of patients with schizophrenia. Five clinically relevant themes were identified
      that affect adherence: medication efficacy, external factors (such as patient
      support and therapeutic alliance), insight, side effects, and attitudes toward
      medication. Importance ratings of these factors differed significantly between
      professionals and carers and patients. Professionals, carers, and patients do not
      have a shared understanding of which factors are important in patients'
      medication adherence behavior. Adherence may be positively influenced if
      professionals focus on the positive aspects of medication, on enhancing insight,
      and on fostering a positive therapeutic relationship with patients and carers.

PMID- 16887890
TI  - Psychotic spectrum disorders and alcohol abuse: a review of pharmacotherapeutic
      strategies and a report on the effectiveness of naltrexone and disulfiram.
AB  - The rate of substance-use disorders in patients with mental illnesses within the
      psychotic spectrum, such as schizophrenia, schizoaffective disorder, and bipolar
      disorder, is higher than the rate observed in the general population and is
      associated with significant morbidity and mortality. Although there are currently
      3 medications approved by the Food and Drug Administration for the treatment of
      alcohol dependence, no medications have been approved for the specific treatment
      of dually diagnosed patients. A small but growing body of literature supports the
      use of 2 of these medications, disulfiram and naltrexone, in dually diagnosed
      individuals. This article outlines a review of the literature about the use of
      disulfiram and naltrexone for alcoholism and in patients with comorbid mental
      illness. In addition, results are presented of a 12-week randomized clinical
      trial of disulfiram and naltrexone alone and in combination for individuals with
      Axis I disorders and alcohol dependence who were also receiving intensive
      psychosocial treatment. Individuals with a psychotic spectrum disorder, including
      schizophrenia, schizoaffective disorder, and bipolar disorder, had worse alcohol
      outcomes than those without a psychotic spectrum disorder. Individuals with a
      psychotic spectrum disorder had better alcohol-use outcomes on an active
      medication compared with placebo, but there was no clear advantage of disulfiram
      or naltrexone or of the combination. Retention rates and medication compliance in
      the study were high and exceeded 80%. Pharmacotherapeutic strategies should take
      into account the advantages and disadvantages of each medication. Future
      directions of pharmacotherapeutic options are also discussed.

PMID- 16887891
TI  - Changes in nicotine intake and cigarette use over time in two nationally
      representative cross-sectional samples of smokers.
AB  - Population surveys have observed decreases in cigarette use over time among
      smokers. These decreases have probably been influenced by tobacco control
      measures implemented over the past several decades, but few data exist on whether
      smokers have also reduced their nicotine intake. The authors examined data from
      two cross-sectional National Health and Nutrition Examination Surveys (NHANES),
      conducted in 1988-1994 and 1999-2002. Laboratory, examination, and interview data
      from current smokers not reporting nicotine intake from other sources were
      examined. From NHANES III (1988-1994) to NHANES 1999-2002, the average number of
      cigarettes smoked per day (CPD) fell by nearly 15% (three cigarettes), while the
      mean serum cotinine level fell by 13% (30 ng/ml). Finer breakdowns of CPD data in
      each time period suggested that most of the change occurred in the lower (<10
      CPD) and higher (>or=20 CPD) smoking categories. These data suggest that CPD may
      represent a proxy for exposure to nicotine and perhaps other tobacco smoke
      constituents on the population level, since the decline in serum cotinine levels
      observed among smokers closely paralleled the decline in self-reported CPD
      between 1988-1994 and 1999-2002. In addition, these data are inconsistent with
      the hypothesis that the remaining population of smokers is becoming more
      dependent on nicotine over time.

PMID- 16887892
TI  - Estimating in real time the efficacy of measures to control emerging communicable
      diseases.
AB  - Controlling an emerging communicable disease requires prompt adoption of measures
      such as quarantine. Assessment of the efficacy of these measures must be rapid as
      well. In this paper, the authors present a framework to monitor the efficacy of
      control measures in real time. Bayesian estimation of the reproduction number R
      (mean number of cases generated by a single infectious person) during an outbreak
      allows them to judge rapidly whether the epidemic is under control (R < 1). Only
      counts and time of onset of symptoms, plus tracing information from a subset of
      cases, are required. Markov chain Monte Carlo and Monte Carlo sampling are used
      to infer the temporal pattern of R up to the last observation. The operating
      characteristics of the method are investigated in a simulation study of severe
      acute respiratory syndrome-like outbreaks. In this particular setting, control
      measures lacking efficacy (R > or = 1.1) could be detected after 2 weeks in at
      least 70% of the epidemics, with less than a 5% probability of a wrong
      conclusion. When control measures are efficacious (R = 0.5), this situation may
      be evidenced in 68% of the epidemics after 2 weeks and 92% of the epidemics after
      3 weeks, with less than a 5% probability of a wrong conclusion.

PMID- 16887893
TI  - Age at natural menopause in women exposed to diethylstilbestrol in utero.
AB  - Age at natural menopause is related to several health outcomes, including
      cardiovascular disease and overall mortality. Age at menopause may be influenced
      by the number of follicles formed during gestation, suggesting that prenatal
      factors could influence menopausal age. Diethylstilbestrol (DES), a nonsteroidal
      estrogen widely prescribed during the 1950s and 1960s, is related to reproductive
      tract abnormalities, infertility, and vaginal cancer in prenatally exposed
      daughters but has not been studied in relation to age at menopause. The authors
      used survival analyses to estimate the risk of natural menopause in 4,210 DES
      exposed versus 1,829 unexposed US women based on responses to questionnaires
      mailed in 1994, 1997, and 2001. DES-exposed women were 50% more likely to
      experience natural menopause at any given age (hazard ratio = 1.49, 95%
      confidence interval: 1.28, 1.74). Among women for whom dose information was
      complete, there were dose-response effects, with a greater than twofold risk for
      those exposed to >10,000 mg. The causal mechanism for earlier menopause may be
      related to a smaller follicle pool, more rapid follicle depletion, or changes in
      hormone synthesis and metabolism in DES-exposed daughters. Age at menopause has
      been related, albeit inconsistently, to several exposures, but, to the authors'
      knowledge, this is the first study to suggest that a prenatal exposure may
      influence reproductive lifespan.

PMID- 16887894
TI  - What is the influence of weight change on forearm bone mineral density in peri-
      and postmenopausal women? The health study of Nord-Trondelag, Norway.
AB  - Weight loss in the elderly increases bone loss and the risk of fractures,
      especially at the hip and spine. The influence of weight change on non-weight
      bearing parts of the skeleton is less well known. The purpose of this study was
      to investigate an association between weight change during the peri- and
      postmenopausal years and forearm bone mineral density (BMD). Among 8,856 women
      aged 45-60 years attending the first Health Study of Nord-Trondelag, Norway (HUNT
      I, 1984-1986), a random sample of 2,795 women was invited to forearm densitometry
      (single x-ray absorptiometry technology) at HUNT II (1995-1997), after a mean
      period of 11.3 years. A total of 2,005 women (mean age: 65.1 years) were
      eligible. The mean weight had increased 3.4 kg; the gain was greater in the
      youngest women. A total of 382 women (19.1%) had lost and 1,331 women (66.3%) had
      gained weight. Weight change explained little of the BMD variance, 0.7% and 0.4%
      for weight loss and weight gain, respectively. Weight loss was an independent and
      statistically significant negative predictor of BMD, adjusted for body weight,
      age, age at menopause, smoking, and ovarian hormone treatment, particularly among
      women with a baseline body mass index greater than 25 kg/m2. No independent
      association between weight gain and forearm BMD was found.

PMID- 16887895
TI  - Isolation and characterization of IRO2, a novel iron-regulated bHLH transcription
      factor in graminaceous plants.
AB  - To clarify the molecular mechanism that regulates iron (Fe) acquisition in
      graminaceous plants, a time-course analysis of gene expression during Fe
      deficiency stress was conducted using a rice 22K oligo-DNA microarray. Twenty-one
      genes for proteins that function in gene regulation were induced by Fe
      deficiency. Of these genes, a putative basic helix-loop-helix (bHLH)
      transcription factor gene, named OsIRO2, was strongly expressed in both roots and
      shoots during Fe deficiency stress. The expression of OsIRO2 was induced
      exclusively by Fe deficiency, and not by deficiencies in other metals. Expression
      of the barley HvIRO2 gene, which is a homologue of OsIRO2, was also induced by Fe
      deficiency. An in silico search revealed that IRO2 is highly conserved among
      graminaceous plants, which include wheat, sorghum, and maize. The cyclic
      amplification and selection of targets (CASTing) technique revealed that OsIRO2
      bound preferentially to the sequence 5'-ACCACGTGGTTTT-3', and the electrophoretic
      mobility shift assay revealed 5'-CACGTGG-3' as the core sequence for OsIRO2
      binding. Sequences similar to the OsIRO2-binding sequence were found upstream of
      several genes that are involved in Fe acquisition, such as OsNAS1, OsNAS3,
      OsIRT1, OsFDH, OsAPT1, and IDS3. The core sequence of the OsIRO2-binding sequence
      occurred more frequently in the upstream regions of Fe deficiency-inducible genes
      than in the corresponding regions of non-inducible genes. These results suggest
      that IRO2 is involved in the regulation of gene expression under Fe-deficient
      conditions.

PMID- 16887896
TI  - A multiplex assay for the detection and mapping of complex glycerol kinase
      deficiency.
AB  - BACKGROUND: Glycerol kinase deficiency (GKD) is an X-linked recessive disorder
      that presents in both isolated and complex forms. The contiguous deletion that
      leads to GKD also commonly affects NR0B1 (DAX1), the gene associated with adrenal
      hypoplasia congenita, and DMD, the Duchenne muscular dystrophy gene. Molecular
      testing to delineate this deletion is expensive and has only limited
      availability. METHODS: We designed a multiplex PCR assay for the detection and
      mapping of a contiguous deletion potentially affecting the IL1RAPL1, NR0B1, GK,
      and DMD genes in a 29-month-old male patient with GKD. RESULTS: Multiplex PCR
      detected a contiguous deletion that involved the IL1RAPL1, NR0B1, GK, and DMD
      genes. Although the patient had a creatine kinase concentration within the
      reference interval, further mapping with PCR revealed that exon 74 was the last
      intact exon at the 3' end of the DMD gene. CONCLUSIONS: Multiplex PCR is an
      effective and inexpensive way to detect and map the contiguous deletion in cases
      of complex GKD. The extension of a deletion to include DMD exon 75 in a patient
      with a creatine kinase concentration within the reference interval suggests that
      this region of the gene may not be essential for protein function.

PMID- 16887897
TI  - Definition of an XML markup language for clinical laboratory procedures and
      comparison with generic XML markup.
AB  - BACKGROUND: Clinical laboratory procedure manuals are typically maintained as
      word processor files and are inefficient to store and search, require substantial
      effort for review and updating, and integrate poorly with other laboratory
      information. Electronic document management systems could improve procedure
      management and utility. As a first step toward building such systems, we have
      developed a prototype electronic format for laboratory procedures using
      Extensible Markup Language (XML). METHODS: Representative laboratory procedures
      were analyzed to identify document structure and data elements. This information
      was used to create a markup vocabulary, CLP-ML, expressed as an XML Document Type
      Definition (DTD). To determine whether this markup provided advantages over
      generic markup, we compared procedures structured with CLP-ML or with the
      vocabulary of the Health Level Seven, Inc. (HL7) Clinical Document Architecture
      (CDA) narrative block. RESULTS: CLP-ML includes 124 XML tags and supports a
      variety of procedure types across different laboratory sections. When compared
      with a general-purpose markup vocabulary (CDA narrative block), CLP-ML documents
      were easier to edit and read, less complex structurally, and simpler to traverse
      for searching and retrieval. CONCLUSION: In combination with appropriate
      software, CLP-ML is designed to support electronic authoring, reviewing,
      distributing, and searching of clinical laboratory procedures from a central
      repository, decreasing procedure maintenance effort and increasing the utility of
      procedure information. A standard electronic procedure format could also allow
      laboratories and vendors to share procedures and procedure layouts, minimizing
      duplicative word processor editing. Our results suggest that laboratory-specific
      markup such as CLP-ML will provide greater benefit for such systems than generic
      markup.

PMID- 16887898
TI  - Performance and clinical utility of a commercial von Willebrand factor collagen
      binding assay for laboratory diagnosis of von Willebrand disease.
AB  - BACKGROUND: Von Willebrand disease (VWD) diagnosis and classification usually
      require a combination of nonspecific and VW-factor (VWF)-specific assays. We
      evaluated the analytical performance of a commercially available collagen-binding
      assay (CBA) and its usefulness in conjunction with other assays for laboratory
      diagnosis of VWD. METHODS: We used a commercial CBA ELISA (Life Technologies) to
      evaluate 3085 plasma samples. We used standard procedures to perform other
      assays, including factor VIII activity (FVIII:C), VWF antigen (VWF:Ag),
      ristocetin cofactor activity, VWF collagen binding capacity (VWF:CB), and VWF
      multimeric analysis. RESULTS: CBA intra- and interassay CVs were <6% and <13%,
      respectively. Reference intervals were 45%-198% for VWF:CB and 0.75-1.32 for the
      VWF:CB/Ag ratio. Of 3085 samples tested, 235 (8%) had results commonly associated
      with VWD. Multimer analysis and phenotypic data in 156 samples identified VWD
      types as: 91 (58%) type 1, 62 (40%) type 2, and 3 (2%) type 3. Of the 91 type 1
      samples, proportional decreases in functional activity were seen in 75 samples
      (82%) according to CBA and in 63 samples (69%) according to the ristocetin
      cofactor assay. Of the type 2 samples, 10 were further identified as probable
      type 2A, 26 as probable type 2B, 12 as probable type 2M, and 14 could not be
      subtyped. VWF:CBA/Ag ratios <0.5 occurred in 83% of VWD type 2A and 2B samples,
      indicating characteristic functional discordance. Mean (SD) VWF:CB values were
      significantly higher in individuals without group O blood [113 (45)] than in
      those with group O blood [83 (32)] (t-test, P = 0.007). CONCLUSIONS: The
      commercial CBA assay produces reliable results and is useful for laboratory
      diagnosis of VWD.

PMID- 16887899
TI  - Proteomic analysis of cerebrospinal fluid changes related to postmortem interval.
AB  - BACKGROUND: The study of proteins with altered production in postmortem
      cerebrospinal fluid (CSF) compared with antemortem CSF may improve the
      understanding of biochemical changes that occur immediately after death. METHODS:
      Two CSF samples (1 antemortem and 1 postmortem) were collected from 7 patients
      and analyzed by 2-dimensional gel electrophoresis. An analysis was also performed
      to identify proteins that showed a correlation between concentration change and
      postmortem interval. Tandem mass spectrometry was used to identify the proteins.
      RESULTS: Fifty-four protein spots were identified that showed a consistent and
      significant change in concentration in the postmortem CSF of all 7 patients (>3.5
      fold, P <0.01). The proteins in these spots derive from a variety of functional
      groups, including cytoskeletal proteins, enzymes involved in glycolysis, and
      proteins that prevent oxidative stress. Fourteen protein spots were found to have
      an increase in production that correlated with postmortem interval. CONCLUSIONS:
      Changes in protein production of postmortem vs antemortem CSF were studied. The
      proteins observed to change production in the postmortem CSF include several
      proteins previously observed as potential stroke biomarkers.

PMID- 16887901
TI  - First international proficiency study on West Nile virus molecular detection.
AB  - BACKGROUND: West Nile virus (WNV) molecular detection is being conducted by a
      growing number of laboratories, but the degree of proficiency may vary between
      them. External quality control is needed. METHODS: We have conducted an
      international quality assurance study on WNV molecular detection. Participating
      laboratories tested noninfectious samples inactivated by heat and gamma
      irradiation. Participants received 7 coded lyophilized samples containing WNV of
      genetic lineages 1a, 1b, and 2 at 2600 to 18 000 000 RNA copies/mL, 3 samples
      containing heterologous flaviviruses, and 2 negative samples. RESULTS: Thirty
      laboratories participated. The average laboratory achieved 50% detection
      probability from 7762 copies/mL onward (probit analysis; 95% CI = 1174-24547
      copies/mL). Lineages 1a and 1b were detected with equal efficiencies, but the
      lineage 2 strain (Ug37) was detected at significantly lower rates. Only 27% of
      participants were able to detect the 6 samples containing > or =1.8 x 10(4)
      copies/mL. Three laboratories generated false-positive results in negative
      samples. Six of 30 laboratories reported correct strain identification in 3
      samples containing non-WNV flaviviruses. We observed a significant positive
      correlation between the capability of detecting non-WNV flaviviruses and
      detecting WNV lineage 2. CONCLUSIONS: Most participants showed good performance
      in detecting lineage 1 WNV, the predominant virus in the Northern Hemisphere. The
      inability of some laboratories to detect even highly concentrated lineage 2 WNV
      downgraded the overall outcome. The lineage 2 material received through this
      study will provide laboratories with the necessary template for improving their
      assays. Such material is otherwise hard to obtain.

PMID- 16887900
TI  - Protease inhibitor-associated dyslipidemia in HIV-infected patients is strongly
      influenced by the APOA5-1131T->C gene variation.
AB  - BACKGROUND: Hyperlipidemia associated with the protease inhibitor (PI) component
      of highly active antiretrovial treatment can lead to accelerated atherosclerosis.
      The apolipoprotein A-V (APOA5) gene, which affects VLDL production and lipolysis,
      may play a role in PI-induced hyperlipidemia, particularly in individuals with
      the APOA5-1131T-->C genotype. METHODS: We measured lipoprotein changes in HIV
      positive patients (n = 229) who had been followed for 5 years. For statistical
      analyses, we segregated the patients with respect to PI treatment and APOA5-1131T
      ->C genotype. RESULTS: The frequency of the C allele was 0.08, similar to that in
      the general population. We found a strong effect of the APOA5-1131T-->C genotype
      among patients receiving PIs. Carriers of the C allele had consistently increased
      mean (SD) triglyceride concentrations compared with noncarriers after 1 year
      [2.11 (1.62) vs 3.71 (4.27) mmol/L; P = 0.009], 2 years [2.48 (2.09) vs 4.02
      (4.05) mmol/L, P = 0.050], 3 years [2.32 (1.71) vs 4.13 (4.26) mmol/L; P =
      0.013], 4 years [2.90 (2.95) vs 5.35 (7.12) mmol/L; P was not significant], and 5
      years [4.25 (5.58) vs 9.23 (9.63) mmol/L; P was not significant]. We observed the
      same effect on total cholesterol concentrations: after 1 year [4.93 (1.31) vs
      5.87 (1.66) mmol/L; P = 0.006], 2 years [5.03 (1.12) vs 6.42 (2.48) mmol/L; P =
      0.001], 3 years [5.11 (1.17) vs 6.38 (2.43) mmol/L; P = 0.009], 4 years [5.49
      (1.71) vs 6.78 (3.03) mmol/L; P was not significant], and 5 years [5.56 (1.75) vs
      7.90 (3.60) mmol/L; P was not significant]. HDL cholesterol showed a progressive
      reduction, leading to a considerably higher cholesterol/HDL cholesterol ratio
      after 3 years. CONCLUSION: Variability in the APOA5 gene predisposes patients
      with HIV, particularly those treated with PI, to severe hyperlipidemia.

PMID- 16887902
TI  - Genome sequence comparison reveals independent inactivation of the caspase-15
      gene in different evolutionary lineages of mammals.
AB  - We have recently demonstrated that placental mammalian species such as pig and
      dog express a novel proapoptotic protease, caspase-15, whereas mouse and humans
      lack this enzyme. Here we investigated the evolutionary fate of the caspase-15
      gene in different mammalian lineages by analyzing whole-genome shotgun sequences
      of 30 mammalian species for the presence of caspase-15 orthologs. Caspase-15 gene
      sequences were found in representatives of all major mammalian clades except for
      the superorders Afrotheria (tenrec, rock hyrax, and elephant) and
      Euarchontoglires (rodents, rabbit, tree shrew, and primates), which either lacked
      any caspase-15-like sequences or contained mutated remnants of the caspase-15
      gene. Polymerase chain reaction screenings confirmed the results of the database
      searches and showed that the caspase-15 gene is expressed not only in various
      placental mammals but also in the marsupial, Monodelphis domestica. The observed
      species distribution implies that caspase-15 has originated in an early ancestor
      of modern mammals and has been conserved, over more than 180 Myr, in marsupials
      and many placental mammals, whereas it was independently lost in 2
      phylogenetically distant clades of placental mammals, that is, Afrotheria and
      Euarchontoglires. Our data suggest that the inactivation of the caspase-15 gene
      was not counteracted by, and may even have been driven by, evolutionary
      constraints in these clades, and therefore, caution against the uncritical use of
      gene absence for the inference of phylogenetic relationships.

PMID- 16887903
TI  - Impacts of gene essentiality, expression pattern, and gene compactness on the
      evolutionary rate of mammalian proteins.
AB  - Understanding the determinants of the rate of protein sequence evolution is of
      fundamental importance in evolutionary biology. Many recent studies have focused
      on the yeast because of the availability of many genome-wide expressional and
      functional data. Yeast studies revealed a predominant role of gene expression
      level and a minor role of gene essentiality in determining the rate of protein
      sequence evolution. Whether these rules apply to complex organisms such as
      mammals is unclear. Here we assemble a list of 1,138 essential and 2,341
      nonessential mouse genes based on targeted gene deletion experiments and report a
      significant impact of gene essentiality on the rate of mammalian protein
      evolution. Gene expression level has virtually no effect, although tissue
      specificity in expression pattern has a strong influence. Unexpectedly, gene
      compactness, measured by average intron size and untranslated region length, has
      the greatest influence. Hence, the relative importance of the various factors in
      determining the rate of mammalian protein evolution is gene compactness > gene
      essentiality approximately tissue specificity > expression level. Our results
      suggest a considerable variation in rate determinants between unicellular
      organisms such as the yeast and multicellular organisms such as mammals.

PMID- 16887904
TI  - Conservation of distantly related membrane proteins: photosynthetic reaction
      centers share a common structural core.
AB  - Photosynthesis was established on Earth more than 3 billion years ago. All
      available evidences suggest that the earliest photosynthetic organisms were
      anoxygenic and that oxygen-evolving photosynthesis is a more recent development.
      The reaction center complexes that form the heart of the energy storage process
      are integral membrane pigment proteins that span the membrane in vectorial
      fashion to carry out electron transfer. The origin and extent of distribution of
      these proteins has been perplexing from a phylogenetic point of view mostly
      because of extreme sequence divergence. A series of integral membrane proteins of
      known structure and varying degrees of sequence identity have been compared using
      combinatorial extension-Monte Carlo methods. The proteins include photosynthetic
      reaction centers from proteobacteria and cyanobacterial photosystems I and II, as
      well as cytochrome oxidase, bacteriorhodopsin, and cytochrome b. The reaction
      center complexes show a remarkable conservation of the core structure of 5
      transmembrane helices, strongly implying common ancestry, even though the
      residual sequence identity is less than 10%, whereas the other proteins have
      structures that are unrelated. A relationship of sequence with structure was
      derived from the reaction center structures; with characteristic decay length of
      1.6 A. Phylogenetic trees derived from the structural alignments give insights
      into the earliest photosynthetic reaction center, strongly suggesting that it was
      a homodimeric complex that did not evolve oxygen.

PMID- 16887905
TI  - Epigenetic regulation of human trophoblastic cell migration and invasion.
AB  - Pivotal to successful mammalian reproduction is the ability of a developing
      embryo to implant to the uterine wall and establish a nutrient supply via
      placentation. Herein, we have examined the potential epigenetic regulation of
      human trophoblastic cell migration and invasion by use of the choriocarcinoma
      cell line, BeWo. Treatment of BeWo cells with a DNA methyltransferase inhibitor,
      5'-aza-2'-deoxycytidine (AZA), resulted in conversion of cell morphology to a
      nonmigratory phenotype. This was exemplified by the ability of AZA to prevent
      BeWo cell migration in wound healing and transwell migration assays. AZA
      consequently inhibited BeWo cell invasion through reconstituted basement
      membrane. Examination of components of the adherens junction complex pivotal for
      determination of cell phenotype revealed that AZA specifically increased the mRNA
      level of E-cadherin and plakoglobin (gamma-catenin), but not alpha-catenin and
      beta-catenin. AZA also increased the gene promoter activity of both plakoglobin
      and E-cadherin. Protein levels of both plakoglobin and E-cadherin were increased
      by AZA, and AZA enhanced their localization to sites of intercellular contact.
      Forced expression of plakoglobin and E-cadherin abrogated BeWo cell migration,
      indicative that repression of these genes was required for BeWo cell migration.
      Small interfering RNA-mediated depletion of the individual DNA methyltransferase
      (DNMT) molecules did not affect plakoglobin and E-cadherin promoter activity or
      BeWo cell migration. However, increases in plakoglobin and E-cadherin promoter
      activity and inhibition of BeWo cell migration was achieved with small
      interfering RNA-mediated depletion of both DNMT-3a and DNMT-3b. Epigenetic
      regulation of plakoglobin and E-cadherin is therefore pivotal for appropriate
      trophoblastic invasion in vitro.

PMID- 16887906
TI  - Isoform-specific regulation of uridine diphosphate-glucuronosyltransferase 2B
      enzymes in the human prostate: differential consequences for androgen and
      bioactive lipid inactivation.
AB  - Androgens as well as monohydroxy-fatty acids are implicated in the pathogenesis
      of prostate cancer. Like a huge variety of endo- and xenobiotics, they are
      eliminated as glucuronide conjugates formed by uridine diphosphate
      glucuronosyltransferase (UGT) enzymes. In the present study, we observe that
      treatment of the prostate cancer cells LNCaP with natural and synthetic
      androgens, IL-1alpha, or epidermal growth factor (EGF) differently modulates the
      glucuronidation of androgen and bioactive lipid metabolites. Indeed,
      glucuronidation of 5alpha-androstane-3alpha,17beta-diol and 13
      hydroxyoctadecadienoic acid was drastically reduced, whereas 12
      hydroxyeicosatetraenoic acid conjugation by UGT was increased after androgen
      treatment. These effects reflected the reduction of UGT2B10, -B15, and -B17
      enzyme expression, and the activation of the UGT2B11 gene. In human prostate
      epithelial cells, only UGT2B11 and -B15 mRNAs are detected and are regulated by
      androgens in a similar manner as in LNCaP cells. In LNCaP cells, IL-1alpha and
      EGF also regulate UGT2B expression in an isoform-specific manner; IL-1alpha
      induced UGT2B10 and reduced UGT2B17, while having no effects on UGT2B11 mRNA
      levels. EGF treatment resulted in a decreased UGT2B17 expression, whereas UGT2B10
      and -B11 mRNA remained at their basal levels. Overall, these results demonstrate
      that in the human prostate, androgens do not only affect their own inactivation
      but also influence the levels of monohydroxy-fatty acids by regulating the
      expression of UGT2B enzymes in an isoform-specific manner. These differential
      effects of androgens, IL-1alpha, and EGF on lipid metabolism likely constitute an
      additional mechanism by which these endogenous factors promote prostate cancer
      development.

PMID- 16887907
TI  - Neutral endopeptidase expressed by decidualized stromal cells suppresses akt
      phosphorylation and deoxyribonucleic acid synthesis induced by endothelin-1 in
      human endometrium.
AB  - Endothelin-1 (ET-1) in human endometrium has been proposed to have a potential
      paracrine role, for its receptors are also present within this tissue. In
      addition, the expression of ET-1 varies during the menstrual cycle, and
      therefore, ET-1 may be involved in the cyclic change of the human endometrium,
      such as proliferation and decidualization. However, neither the inactivation of
      ET-1 in the endometrium nor the paracrine effect of ET-1 on endometrial cells has
      been determined. We investigated the production of ET-1 and the presence of
      neutral endopeptidase (NEP), which cleaves and inactivates ET-1, in primary
      cultured human endometrial cells. We found primary cultured endometrial
      epithelial cells, not stromal cells, to be the major source of ET-1. Western blot
      analysis and RT-PCR demonstrated that NEP was predominantly expressed by
      endometrial stromal cells. We also demonstrated that ET-1 stimulated the
      phosphorylation of Akt and DNA synthesis in endometrial stromal cells via the
      ET(A) receptor and phospahtidylinositol-3 kinase signaling pathways. The effect
      of ET-1 was regulated by NEP expressed by stromal cells. We also found that
      conditioned medium containing ET-1 from endometrial epithelial cell culture
      stimulated phosphorylation of Akt via the ET(A) receptor. In conclusion, ET-1 has
      a paracrine effect of Akt phosphorylation and cell proliferation on endometrial
      stromal cells, which occurs via the ET(A) receptor and phospahtidylinositol-3
      kinase signaling pathways, and is regulated by cell-surface NEP.

PMID- 16887908
TI  - Ghrelin increases neuropeptide Y and agouti-related peptide gene expression in
      the arcuate nucleus in rat hypothalamic organotypic cultures.
AB  - Ghrelin, which was identified from the rat stomach, is a potent stimulant for
      food intake. Several lines of evidence suggest that the orexigenic action of
      ghrelin is mediated via the neuropeptide Y (NPY) neurons in the arcuate nucleus,
      although the detailed mechanisms by which ghrelin stimulates NPY neurons are not
      clear. In this study, we examined the gene regulation of NPY and agouti-related
      peptide (AGRP), another orexigenic peptide synthesized in the NPY neurons, in the
      arcuate nucleus by ghrelin in hypothalamic organotypic cultures. Incubation of
      the hypothalamic explants with ghrelin significantly increased NPY and AGRP mRNA
      expression in the presence, but not absence, of dexamethasone. Glucocorticoids
      were also necessary for ghrelin action in vivo because an intracerebroventricular
      injection of ghrelin significantly increased NPY and AGRP mRNA expression in the
      arcuate nucleus only in sham-operated, but not in adrenalectomized rats. The
      stimulatory effects of ghrelin on gene expression were not blocked by a sodium
      channel blocker tetrodotoxin in the organotypic cultures. Ghrelin also increased
      NPY heteronuclear (hn) RNA expression, the first transcript that has been used as
      an indicator for gene transcription. The stimulatory effects of ghrelin on NPY
      gene expression were abolished in the presence of cycloheximide, which blocks
      translation, suggesting that de novo protein synthesis is required for ghrelin
      action. These data suggest that ghrelin stimulates NPY and AGRP gene expression
      independently of action potentials only in the presence of glucocorticoids.
      Furthermore, our data demonstrate stimulatory action of ghrelin on NPY gene
      transcription, which requires de novo protein synthesis.

PMID- 16887909
TI  - Differential expression of activator protein-1 proteins in the pineal gland of
      Syrian hamster and rat may explain species diversity in arylalkylamine N
      acetyltransferase gene expression.
AB  - Species differences have been reported for the nighttime regulation of
      arylalkylamine N-acetyltransferase (AA-NAT), the melatonin rhythm-generating
      enzyme. In particular, de novo synthesis of stimulatory transcription factors is
      required for Aa-nat transcription in the Syrian hamster but not in the rat pineal
      gland. The present work investigated the contribution of phosphorylated cAMP
      responsive element-binding protein, c-FOS, c-JUN, and JUN-B in the regulation of
      Aa-nat transcription in Syrian hamsters compared with rats. The nighttime pattern
      of cAMP-responsive element-binding protein phosphorylation and regulation by
      norepinephrine observed in the Syrian hamster was similar to those reported in
      the rat. On the contrary, strong divergences in c-FOS, c-JUN, and JUN-B
      expression were observed between both species. In Syrian hamster, predominant
      expression of c-FOS and c-JUN was observed at the beginning of night, whereas a
      predominant expression of c-JUN and JUN-B was observed in the late night in rat.
      The early peak of c-FOS and c-JUN, known to form a stimulatory transcription
      dimer, suggests that they are involved in the nighttime stimulation of Aa-nat
      transcription. Indeed, early-night administration of a protein synthesis
      inhibitor (cycloheximide) markedly decreased AA-NAT mRNA levels in Syrian
      hamster. In the rat, high levels of JUN-B and c-JUN, constituting an inhibitory
      transcription dimer, are probably involved in the late-night inhibition of Aa-nat
      transcription. Early-night administration of cycloheximide actually increased AA
      NAT mRNA levels toward the late night. Therefore, composition and timing of the
      pineal activator protein-1 complexes differ between rat and Syrian hamster and
      may be an activator (Syrian hamster) or an inhibitor (rat) of Aa-nat
      transcription.

PMID- 16887910
TI  - Roles of 11beta-hydroxysteroid dehydrogenase in fish spermatogenesis.
AB  - In fish spermatogenesis, the main action of progestins is generally regarded as
      the induction of sperm maturation. Our previous in vitro study demonstrated that
      a progestin, 17alpha,20beta-dihydroxy-4-pregnen-3-one (DHP), induced the
      initiation of meiosis in spermatogenesis in the Japanese eel (Anguilla japonica).
      In the present study, to elucidate the molecular mechanisms underlying the action
      of DHP, we attempted to clone cDNAs encoding genes whose expression was induced
      by DHP in eel testis, using cDNA subtraction. One of the cDNAs we isolated
      encodes eel 11beta-hydroxysteroid dehydrogenase short form (e11beta-HSDsf), and
      Northern blot and RT-PCR analysis showed that transcripts of e11beta-HSDsf in
      testis were induced by DHP. The recombinant e11beta-HSDsf had 11beta
      dehydrogenase activity, metabolizing cortisol to cortisone, and 11beta
      hydroxytestosterone to 11-ketotestosterone (11-KT). In vitro experiments revealed
      that eel immature testis had 11beta-dehydrogenase activity, and DHP treatment
      enhanced the activity. To understand the role of 11beta-HSD in spermatogenesis,
      we examined the direct effects of cortisol on eel spermatogenesis using an organ
      culture system. Cortisol induced DNA replication in spermatogonia and enhanced
      the spermatogonial proliferation induced by 11-KT. However, excess cortisol
      inhibited proliferation. In addition, 11-KT production was induced in testicular
      fragments incubated with cortisol. These results suggest that optimal levels of
      cortisol induced spermatogonial mitosis by increasing 11-KT production.
      Furthermore, two possible roles of DHP on spermatogenesis, via the up-regulation
      of 11beta-HSD expression, are suggested: positive feedback control of 11-KT
      production and the modulation of cortisol levels to protect testes from excess
      circulating cortisol.

PMID- 16887911
TI  - Inverse relationship between nitric oxide synthases and endothelin-1 synthesis in
      bovine corpus luteum: interactions at the level of luteal endothelial cell.
AB  - Endothelin-1 (ET-1) and nitric oxide (NO) play pivotal roles in corpus luteum
      (CL) function. The present study examined the interplay between NO and ET-1
      synthesis in the bovine CL. We found similar inducible and endothelial NO
      synthase (iNOS and eNOS, respectively) activities in the young CL (d 1-5)
      expressing the highest levels of both eNOS and iNOS mRNA. These values later
      declined at mid-cycle (d 8-15) and remained low at later stages (d 16-18).
      Luteolysis, initiated by prostaglandin F2alpha analog administration, further
      reduced NOS mRNA and by 24 h, NOS values dropped to approximately 15% of those at
      mid-cycle. eNOS protein levels followed a similar pattern to its mRNA. Because
      endothelial cells (ECs) are the main site for ET-1 and NO production in the CL,
      we examined the direct effects of the NO donor, NONOate on luteal ECs (LECs).
      Elevated NO levels markedly decreased ET-1 mRNA, and peptide concentrations in
      cultured and freshly isolated LECs in a dose-dependent manner. In agreement, NOS
      inhibitor, NG-nitro-l-arginine methyl ester, stimulated ET-1 mRNA expression in
      these cells. Interestingly, NO also up-regulated prostaglandin F2alpha receptors
      in LECs. These data show that there is an inverse relationship between NOS and ET
      1 throughout the CL life span, and imply that this pattern may be the result of
      their interaction within the resident LECs. NOS are expressed in a
      physiologically relevant manner: elevated NO at an early luteal stage is likely
      to play an important role in angiogenesis, whereas reduced levels of NO during
      luteal regression may facilitate the sustained up-regulation of ET-1 levels
      during luteolysis.

PMID- 16887912
TI  - Prevention of adipose tissue depletion during food deprivation in angiotensin
      type 2 receptor-deficient mice.
AB  - Angiotensin (Ang) II is produced locally in various tissues, but its role in the
      regulation of tissue metabolism is still unclear. Recent studies have revealed
      the role of type 2 Ang II receptor (AT2R) in the control of energy homeostasis
      and lipid metabolism. The contribution of the AT2R to adaptation to starvation
      was tested using AT2R-deficient (AT2R (y)(/-)) mice. Fasted AT2R (y)(/-) mice
      exhibited a lower loss of adipose tissue weight associated to a decreased free
      fatty acid (FFA) release from stored lipids than the controls. In vitro studies
      show that Ang II causes an AT1R-mediated antilipolytic effect in isolated
      adipocytes. AT1R expression is up-regulated by fasting in both genotypes, but the
      increase is more pronounced in AT2R (y/-) mice. In addition, the increased muscle
      beta-oxidation displayed in AT2R (y/-) mice on a fed state, persists after
      fasting compared with wild-type mice. In liver from fed mice, AT2R deficiency did
      not modify the expression of genes involved in fatty acid oxidation. However, in
      response to fasting, the large increase of the expression of this subset of genes
      exhibited by wild-type mice, was impaired in AT2R (y/-) mice. Taken together,
      decreased lipolytic capacity and increased muscle fatty acid oxidation
      participate in the decreased plasma FFA observed in fasted AT2R (y/-) mice and
      could account for the lower FFA metabolism in the liver. These data reveal an
      important physiological role of AT2R in metabolic adaptations to fasting.

PMID- 16887913
TI  - Orphanin FQ/nociceptin is a physiological regulator of prolactin secretion in
      female rats.
AB  - Orphanin FQ/nociceptin (OFQ/N), the most recently identified endogenous opioid
      peptide, stimulates prolactin secretion in both male and female rats. OFQ/N,
      however, did not elicit this stimulatory effect through the mu-, delta-, or kappa
      opiate receptor subtype. The role OFQ/N plays in prolactin regulation under
      physiological conditions and its mechanism of action are not known. The purpose
      of these studies was to determine the physiological significance and
      pharmacological specificity of the prolactin secretory response to OFQ/N. In
      addition, the role of the tuberoinfundibular dopaminergic (TIDA) neurons in
      mediating this response was examined. Opioid receptor-like-1 (ORL-1) receptors
      were blocked by pretreatment with compound B (Comp B), a purported OFQ/N
      antagonist, or receptor synthesis was disrupted by pretreatment with ORL-1
      receptor antisense oligonucleotides. The prolactin secretory response to OFQ/N
      administration in diestrous females was measured. Furthermore, the suckling
      induced prolactin response was also determined after Comp B pretreatment. TIDA
      neuronal activity was quantified in diestrous female rats to determine whether
      OFQ/N stimulates prolactin release by inhibiting TIDA neurons. OFQ/N
      significantly inhibited the TIDA neurons by 1 min, preceding the prolactin
      secretory response. Both Comp B and antisense pretreatment blocked the
      stimulatory effects of OFQ/N on prolactin release, and Comp B abolished the
      suckling-induced prolactin response. These studies indicate that OFQ/N is a
      potent stimulus for prolactin secretion in female rats and that it mediates this
      effect by rapid and transient inhibition of TIDA neuronal activity. Furthermore,
      OFQ/N plays a physiologically significant role in the regulation of prolactin
      secretion during lactation, and it mediates its effects via actions at the ORL-1
      receptor subtype.

PMID- 16887914
TI  - Interleukin-1beta signals through a c-Jun N-terminal kinase-dependent inducible
      nitric oxide synthase and nitric oxide production pathway in Sertoli epithelial
      cells.
AB  - Our recent Sertoli cell (SC) studies showed that the c-Jun N-terminal kinase
      (JNK) and inducible cyclooxygenase-2 (COX-2) pathways are key regulatory
      components of IL (IL-1alpha, IL-1beta, and IL-6) expression and START-domain
      containing StARD1 and StARD5 proteins. IL-1beta regulates SC autocrine/paracrine
      activities and subsequently influences developing germ cells and spermatogenesis.
      This study was designed to evaluate whether IL-1beta mediates high-output
      inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO)
      production in these specialized epithelial cells and characterize gonadotropin
      and cytokine-regulation of NO. Purified SCs were maintained in serum-free
      cultures and treated with FSH (100 ng-1 microg/ml) or IL-1beta (10 ng/ml) in time
      course studies. To determine obligatory intracellular pathways, treatments were
      conducted with or without activity inhibitors: COX-2 selective (NS-398, 10
      microM) or JNK (SP600125, 10 microM) for 1, 3, 6, and 24 h. NOS mRNAs and
      proteins were evaluated by RT-PCR and Western analysis, respectively. NO and
      reactive oxygen species were measured by flow cytometry and ELISA. IL-1beta
      transiently induces intracellular NO (30 min) but not reactive oxygen species.
      Subsequently, iNOS mRNA and protein expression (3-6 h) significantly increased
      after IL-1beta but not FSH stimulation, and in time-dependent manner, markedly
      increased extracellular NO (24 h, 8-fold). No change in the constitutive
      endothelial NOS isoform was observed. Inhibition of JNK, but not COX-2, activity
      inhibits IL-1beta-induced iNOS expression and NO production. Such findings
      suggest that intra- and extracellular NO within the tubule may alert SCs
      monitoring the microenvironment to an aberrant cytokine, triggering antioxidant
      and antiinflammatory activities to avoid disruption of spermatogenesis.

PMID- 16887915
TI  - Glucocorticoid up-regulates transforming growth factor-beta (TGF-beta) type II
      receptor and enhances TGF-beta signaling in human prostate cancer PC-3 cells.
AB  - Previous studies have shown that dexamethasone (Dex) induces the expression of
      TGF-beta1 in androgen-independent prostate cancer both in vitro and in vivo.
      However, it is not clear whether Dex has a direct effect on the expression of TGF
      beta receptors. In this study, using the androgen-independent human prostate
      cancer cell line, PC-3 cells, we demonstrated that Dex increased the expression
      of TGF-beta receptor type II (TbetaRII), but not TGF-beta receptor type I
      (TbetaRI) in a time- and dose-dependent manner. The up-regulation of TbetaRII
      expression by Dex was mediated by glucocorticoid receptor and occurred at the
      transcriptional level. Dex also enhanced TGF-beta1 signaling and increased the
      expression of cyclin-dependent kinase inhibitors p15(INK4B) (p15) and p27(KIP1)
      (p27), which are the target genes of TGF-beta1 and have been identified as
      inducers of cell cycle arrest at the G1 checkpoint. The antiproliferative effect
      of Dex was partially blocked by anti-TbetaRII antibody, indicating that elevated
      TbetaRII and TGF-beta1 signaling were involved in the antiproliferative effect of
      Dex. Because the TGF-beta1 pathway could not fully explain the antiproliferative
      effect of Dex, we further examined the effects of Dex on the transcriptional
      activity of nuclear factor-kappaB (NF-kappaB) and the expression of IL-6 and
      found that Dex suppressed the transcriptional activity of NF-kappaB and IL-6 mRNA
      expression in PC-3 cells. These results demonstrated that glucocorticoid
      inhibited the proliferation of PC-3 cells not only through enhancing growth
      inhibitory TGF-beta1 signaling, but also through suppressing transcriptional
      activities of NF-kappaB.

PMID- 16887916
TI  - Somatostatin regulates aggressive behavior in an African cichlid fish.
AB  - Animals respond to environmental and social change with plasticity in the neural
      substrates underlying particular behavioral states. In the African cichlid fish
      Astatotilapia burtoni, social dominance status in males is accompanied by reduced
      somatic growth rate as well as increased somatostatin neuron size in the preoptic
      area. Although somatostatin is commonly studied within the context of growth, we
      show here for the first time that this ancient neuropeptide also plays a role in
      controlling social behavior. Somatostatin antagonists increased aggressive
      behavior in a dose-dependent fashion and the potent somatostatin agonist
      octreotide decreased aggression. We cloned and sequenced the genes encoding two
      somatostatin receptor subtypes in this species to study transcription in the
      gonads. When we examined somatostatin receptor gene expression in testes,
      expression of the somatostatin type 3 receptor was negatively correlated with an
      aggressive display and androgen levels. However, octreotide treatment did not
      reduce plasma testosterone or 11-ketotestosterone levels, suggesting that the
      behavioral effects of somatostatin are not mediated by androgens. These results
      show that somatostatin has important effects on social behavior. In dominant male
      A. burtoni, somatostatin may function to contain energetically costly processes
      such as somatic growth and aggressive behavior.

PMID- 16887917
TI  - Sphingosine regulates the transcription of CYP17 by binding to steroidogenic
      factor-1.
AB  - Steroidogenic factor (SF1, Ad4BP, NR5A1) is a nuclear receptor that is essential
      for steroid hormone biosynthesis and endocrine development. Recent
      crystallographic studies have found that phospholipids are ligands for SF1. In
      the present study, our aim was to identify endogenous ligands for SF1 and
      characterize their functional significance in mediating cAMP-dependent
      transcription of human CYP17. Using tandem mass spectrometry, we show that in
      H295R adrenocortical cells, SF1 is bound to sphingosine (SPH) and lyso
      sphingomyelin (lysoSM) under basal conditions and that cAMP stimulation decreases
      the amount of SPH and lysoSM bound to the receptor. Silencing both acid and
      neutral ceramidases using small interfering RNA induces CYP17 mRNA expression,
      suggesting that SPH acts as an inhibitory ligand. SPH antagonized the ability of
      cAMP and the coactivator steroid receptor coactivator-1 to increase CYP17
      reporter gene activity. These studies demonstrate that SPH is a bonafide
      endogenous ligand for SF1 and a negative regulator of CYP17 gene expression.

PMID- 16887918
TI  - Calcium flux in turtle ventricular myocytes.
AB  - The relative contribution of the sarcoplasmic reticulum (SR), the L-type Ca(2+)
      channel and the Na(+)/Ca(2+) exchanger (NCX) were assessed in turtle ventricular
      myocytes using epifluorescent microscopy and electrophysiology. Confocal
      microscopy images of turtle myocytes revealed spindle-shaped cells, which lacked
      T-tubules and had a large surface area-to-volume ratio. Myocytes loaded with the
      fluorescent Ca(2+)-sensitive dye Fura-2 elicited Ca(2+) transients, which were
      insensitive to ryanodine and thapsigargin, indicating the SR plays a small role
      in the regulation of contraction and relaxation in the turtle ventricle.
      Sarcolemmal Ca(2+) currents were measured using the perforated-patch voltage
      clamp technique. Depolarizing voltage steps to 0 mV elicited an inward current
      that could be blocked by nifedipine, indicating the presence of Ca(2+) currents
      originating from L-type Ca(2+) channels (I(Ca)). The density of I(Ca) was 3.2 +/-
      0.5 pA/pF, which led to an overall total Ca(2+) influx of 64.1 +/- 9.3 microM/l.
      NCX activity was measured as the Ni(+)-sensitive current at two concentrations of
      intracellular Na(+) (7 and 14 mM). Total Ca(2+) influx through the NCX during
      depolarizing voltage steps to 0 mV was 58.5 +/- 7.7 micromol/l and 26.7 +/- 3.2
      micromol/l at 14 and 7 mM intracellular Na(+), respectively. In the absence of
      the SR and L-type Ca(2+) channels, the NCX is able to support myocyte contraction
      independently. Our results indicate turtle ventricular myocytes are primed for
      sarcolemmal Ca(2+) transport, and most of the Ca(2+) used for contraction
      originates from the L-type Ca(2+) channel.

PMID- 16887919
TI  - Homer Wheelon, M.D., physiologist, artist, and poet: origins of the tailpieces in
      journals of the American Physiological Society.
AB  - Since 1953, illustrations have been inserted as "tailpieces" at the ends of
      articles in The American Journal of Physiology and The Journal of Applied
      Physiology. The drawings were made by Homer Wheelon, a member of the American
      Physiological Society from 1919 until his death in 1960. Forty-five years after
      his death, Wheelon is unknown, but he contributed 32 publications to the medical
      literature and trained J. Earl Thomas, an important 20th century gastrointestinal
      physiologist. Wheelon was born into poverty in 1883 to itinerant Methodist
      preachers, circumstances that guided his education and career choices. Throughout
      his life, Wheelon exhibited a fondness and talent for art and photography and an
      unusual breadth of intellectual interests and knowledge. Wheelon received a
      bachelor's degree from the University of Washington, then studied at the
      University of Oregon, Northwestern University, and St. Louis University. Earning
      his M.D. from St. Louis University and assuming a faculty position there, Wheelon
      and his graduate student, Thomas, conducted widely recognized gastrointestinal
      research. Returning to Seattle in 1921, Wheelon became a highly respected
      physician and hospital administrator, but he also found time to indulge his
      interest in visual art and poetry. In 1933, inspired by observing a rabbit being
      used in a pregnancy test, Wheelon began to write and illustrate an epic, 322-page
      poem, Rabbit No. 202, illustrations from which became the journals' tailpieces.
      The present study traces Wheelon's personal life and scientific career in an
      attempt to understand this complex man and the origins of his unusual poem and
      its drawings.

PMID- 16887920
TI  - Responses of thoracic spinal neurons to activation and desensitization of cardiac
      TRPV1-containing afferents in rats.
AB  - The purpose of this study was to examine how upper thoracic spinal neurons
      responded to activation and desensitization of cardiac transient receptor
      potential vanilloid-1 (TRPV1)-containing afferent fibers. Extracellular
      potentials of single T3 spinal neurons were recorded in pentobarbital
      anesthetized, paralyzed, and ventilated male rats. To activate cardiac
      nociceptive receptors, a catheter was placed in the pericardial sac to administer
      various chemicals: bradykinin (BK; 10 microg/ml, 0.2 ml), capsaicin (CAP, 10
      microg/ml, 0.2 ml), or a mixture of algesic chemicals (AC; 0.2 ml) containing
      adenosine 10(-3) M, BK, serotonin, histamine, and PGE(2), 10(-5) M for each.
      Spinal neurons that responded to intrapericardial BK and/or CAP were used in this
      study. Results showed that 81% (35/43) of the neurons had excitatory responses to
      both intrapericardial BK and CAP, and the remainder responded to either BK or
      CAP. Intrapericardial resiniferatoxin (RTX) (0.2 microg/ml, 0.2 ml, 1 min), which
      desensitizes TRPV1-containing nerve endings, abolished excitatory responses to
      both BK (n = 8) and CAP (n = 7), and to AC (n = 5) but not to somatic stimuli.
      Intrapericardial capsazepine (1 mg/ml, 0.2 ml, 3 min), a specific antagonist of
      TRPV1, sharply attenuated excitatory responses to CAP in 5/5 neurons, but
      responses to BK in 5/5 neurons was maintained. Additionally, intrapericardial
      capsazepine had no significant effect on excitatory responses to AC in 3/3
      neurons. These data indicated that intrapericardial BK-initiated spinal neuronal
      responses were linked to cardiac TRPV1-containing afferent fibers, but were not
      dependent on TRPV1. Intraspinal signaling for cardiac nociception was mediated
      through CAP-sensitive afferent fibers innervating the heart.

PMID- 16887921
TI  - Sympathetic but not sensory denervation stimulates white adipocyte proliferation.
AB  - White adipocyte proliferation is a hallmark of obesity, but it largely remains a
      mechanistic mystery. We and others previously demonstrated that surgical
      denervation of white adipose tissue (WAT) triggers increases in fat cell number,
      but it is unknown whether this was due to preadipocyte proliferation or
      maturation of existing preadipocytes that allowed them to be counted. In
      addition, surgical denervation severs not only sympathetic but also sensory
      innervation of WAT. Therefore, we tested whether sympathetic WAT denervation
      triggers adipocyte proliferation using 5-bromo-2'-deoxyuridine (BrdU) as a marker
      of proliferation and quantified BrdU-immunoreactive (ir) cells that were co
      labeled with AD-3-ir, an adipocyte-specific membrane protein marker. The
      unilateral denervation model was used for all experiments where Siberian hamster
      inguinal WAT (IWAT) was unilaterally denervated, the contralateral pad was sham
      denervated serving as a within-animal control, and then BrdU was injected
      systemically for 6 days. When IWAT was surgically denervated, severing both
      sympathetic and sensory nerves, tyrosine hydroxylase (TH)-ir, a sympathetic nerve
      marker, and calcitonin gene-related peptide (CGRP)-ir, a sensory nerve marker,
      were significantly decreased, and BrdU+AD-3-ir adipocytes were increased
      approximately 300%. When IWAT was selectively sensory denervated via local
      microinjections of capsaicin, a sensory nerve-specific toxin, CGRP-ir, but not TH
      ir, was decreased, and BrdU+AD-3-ir adipocytes were unchanged. When IWAT was
      selectively sympathetically denervated via local microinjections of 6-hydroxy
      dopamine, a catecholaminergic-specific toxin, TH-ir, but not CGRP-ir, was
      significantly decreased, and BrdU+AD-3-ir adipocytes were increased approximately
      400%. Collectively, these data provide the first direct evidence that sympathetic
      nerves inhibit white adipocyte proliferation in vivo.

PMID- 16887922
TI  - Facilitators and obstacles to sperm banking in young men receiving gonadotoxic
      chemotherapy for cancer: the perspective of survivors and health care
      professionals.
AB  - BACKGROUND: Testicular cancer and Hodgkin's disease are among the most common
      malignancies to affect young men of reproductive age. Although both are
      associated with high rates of infertility, sperm banking (SB) remains
      underutilized by both diagnostic groups. Reasons for this remain elusive.
      METHODS: This study used a qualitative design. In-depth interviews were conducted
      with 20 cancer survivors and 18 health care professionals (HCPs) to examine their
      perspectives on factors that facilitate or hinder SB. Interview data were
      analysed using a mixed approach and a three-step process of data reduction, data
      display and conclusion drawing and verification. RESULTS: Eight factors were
      identified as having an impact on SB, and findings suggest that effective
      promotion of SB involves adequate communication around the severity and personal
      risk for infertility, assessing the importance of patients place on having
      children, emphasizing the benefits of SB and addressing possible obstacles such
      as cost, misperceptions or cultural and other factors. In addition, the
      communicator should be perceived as appealing. CONCLUSIONS: These results are
      conceptually consistent with both the Health Belief Model and the Elaboration
      Likelihood Model of health promotion and are useful in informing HCPs on how to
      better promote SB.

PMID- 16887923
TI  - ART outcome in HIV-infected patients.
AB  - BACKGROUND: To assess assisted reproductive technique (ART) outcome in couples
      affected by human immunodeficiency virus (HIV). METHODS: Intrauterine
      insemination (IUI), IVF and ICSI were performed in 85 couples affected by HIV
      between January 2000 and June 2005. RESULTS: In 33 of the 85 couples, women were
      HIV positive-the clinical pregnancy rate (CPR) and cancellation rate (CR) after
      34 IUI cycles were, respectively, 25 and 18%. The CPR after 26 IVF and 30 ICSI
      cycles were, respectively, 37.5 and 18.8% with CRs of 38.5 and 46.7%,
      respectively. In 38 couples, men were infected-the CPR and CR after 85 IUI cycles
      were, respectively, 14.7 and 20%; 62 ICSI cycles were performed leading to CPR of
      23.4% with a CR of 25%. In 14 couples, the two partners were infected: none of
      the four IUI cycles carried out was successful (CR, 20%); the CPR and CR after 35
      ICSI cycles were, respectively, 12.5% with 31%. All children born had a negative
      HIV test. CONCLUSION: In couples affected by HIV, an acceptable pregnancy rate
      was obtained. The worst results were obtained when both partners were infected.
      The CR was elevated among HIV-infected couples.

PMID- 16887924
TI  - Histological evaluation of the human testis--approaches to optimizing the
      clinical value of the assessment: mini review.
AB  - Testicular biopsy is a crucial assessment in reproductive practice with
      diagnostic and prognostic importance for assisted reproductive technologies
      (ARTs) and risk of testicular neoplasia. Endocrine and genetic tests cannot
      reliably distinguish obstructive azoospermia (OA) from non-obstructive
      azoospermia (NOA) or predict recovery of mature spermatids by testicular sperm
      extraction (TESE). Currently, divergent histological reporting systems and the
      use of imprecise terminology seriously degrade the value of the literature on
      TESE recovery rates and hamper evaluation of treatments and research on genotype
      phenotype relationships. The rising incidence of testis cancer and carcinoma in
      situ (CIS), especially in infertile populations, requires that every effort be
      made for its early detection. We provide a systematic approach to the
      histological classification of spermatogenic disorders and detection of CIS in
      adult patients. We evaluate a large consecutive series of bilateral biopsies from
      infertile men and report (i) the frequency of bilateral or discordant patterns
      that supports the use of bilateral biopsy for comprehensive evaluation and (ii) a
      high prevalence of mixed patterns, particularly within the hypospermatogenesis
      classification, that helps account for reported success of TESE. We propose a new
      diagnosis code for testicular biopsies that addresses the needs of ART clinicians
      and allows data storage and retrieval of value in clinical practice and research.

PMID- 16887926
TI  - On the benefit of assisted reproduction techniques, a comparison of the USA and
      Europe.

PMID- 16887928
TI  - The difference in pregnancy rates between elective single embryo transfer (SET)
      compared to double embryo transfer is dependent on the implantation rates of
      embryos being transferred. Using mathematical modeling to determine when SET
      becomes a viable option.

PMID- 16887929
TI  - Peptide microarray analysis of substrate specificity of the transmembrane Ser/Thr
      kinase KPI-2 reveals reactivity with cystic fibrosis transmembrane conductance
      regulator and phosphorylase.
AB  - Human lemur (Lmr) kinases are predicted to be Tyr kinases based on sequences and
      are related to neurotrophin receptor Trk kinases. This study used homogeneous
      recombinant KPI-2 (Lmr2, LMTK2, Cprk, brain-enriched protein kinase) kinase
      domain and a library of 1,154 peptides on a microarray to analyze substrate
      specificity. We found that KPI-2 is strictly a Ser/Thr kinase that reacts with
      Ser either preceded by or followed by Pro residues but unlike other Pro-directed
      kinases does not strictly require an adjacent Pro residue. The most reactive
      peptide in the library corresponds to Ser-737 of cystic fibrosis transmembrane
      conductance regulator, and the recombinant R domain of cystic fibrosis
      transmembrane conductance regulator was a preferred substrate. Furthermore the
      KPI-2 kinase phosphorylated peptides corresponding to the single site in
      phosphorylase and purified phosphorylase b, making this only the second known
      phosphorylase b kinase. Phosphorylase was used as a specific substrate to show
      that KPI-2 is inhibited in living cells by addition of nerve growth factor or
      serum. The results demonstrate the utility of the peptide library to probe
      specificity and discover kinase substrates and offer a specific assay that
      reveals hormonal regulation of the activity of this unusual transmembrane kinase.

PMID- 16887930
TI  - Modulation of testicular receptor 4 activity by mitogen-activated protein kinase
      mediated phosphorylation.
AB  - Testicular receptor 4 (TR4) is an orphan member of the nuclear receptor
      superfamily. Despite the lack of identified ligands, its functional role has been
      demonstrated both in animals and cell cultures. However, it remains unclear how
      the biological activity of TR4 is regulated without specific ligands. In this
      study, we showed that in the absence of specific ligands the activity of TR4
      could be modulated by mitogen-activated protein kinase (MAPK)-mediated
      phosphorylation of its activation function 1 (AF-1) domain. A mass spectrometry
      based proteome analysis of TR4 expressed in insect cells revealed three
      phosphorylation sites in its AF-1 domain, specifically on Ser(19), Ser(55), and
      Ser(68). Site-directed mutagenesis studies demonstrated the functionality of
      phosphorylation on Ser(19) and Ser(68) but not Ser(55). We also demonstrated that
      MAPK-mediated phosphorylation of the AF-1 domain rendered TR4 a repressor,
      mediated through the preferential recruitment of corepressor RIP140.
      Dephosphorylation of its AF-1 made TR4 an activator due to its selective
      recruitment of coactivator, P300/cyclic AMP-responsive element binding protein
      binding protein-associated factor (PCAF). The biological effects were validated
      by using the wild type TR4 and its constitutive negative (dephosphorylated) and
      constitutive positive (phosphorylated) mutants in the studies of regulation of
      its natural target gene, apoE. This study uncovered, for the first time, a ligand
      independent mechanism underlying the biological activity of TR4 that was mediated
      by MAPK-mediated receptor phosphorylation of AF-1 domain.

PMID- 16887932
TI  - Synergistic effects of peloruside A and laulimalide with taxoid site drugs, but
      not with each other, on tubulin assembly.
AB  - Previous studies on the drug content of pelleted tubulin polymers suggest that
      peloruside A binds in the laulimalide site, which is distinct from the taxoid
      site. In a tubulin assembly system containing microtubule-associated proteins and
      GTP, however, peloruside A was significantly less active than laulimalide,
      inducing assembly in a manner that was most similar to sarcodictyins A and B.
      Because peloruside A thus far seems to be the only compound that mimics the
      action of laulimalide, we examined combinations of microtubule-stabilizing agents
      for synergistic effects on tubulin assembly. We found that peloruside A and
      laulimalide showed no synergism but that both compounds could act synergistically
      with a number of taxoid site agents [paclitaxel, epothilones A/B, discodermolide,
      dictyostatin, eleutherobin, the steroid derivative 17beta-acetoxy-2-ethoxy-6-oxo
      B-homo-estra-1,3,5(10)-trien-3-ol, and cyclostreptin]. None of the taxoid site
      compounds showed any synergism with each other. From an initial study with
      peloruside A and cyclostreptin, we conclude that the synergism phenomenon
      derives, at least in part, from an apparent lowering of the tubulin critical
      concentration with drug combinations compared with single drugs. The apparent
      binding of peloruside A in the laulimalide site led us to attempt construction of
      a pharmacophore model based on superposition of an energy-minimized structure of
      peloruside A on the crystal structure of laulimalide. Although the different
      sizes of the macrocycles limited our ability to superimpose the two molecules,
      atom correspondences that were observed were consistent with the difficulty so
      far experienced in creation of fully active analogs of laulimalide.

PMID- 16887931
TI  - Advances and challenges in liquid chromatography-mass spectrometry-based
      proteomics profiling for clinical applications.
AB  - Recent advances in proteomics technologies provide tremendous opportunities for
      biomarker-related clinical applications; however, the distinctive characteristics
      of human biofluids such as the high dynamic range in protein abundances and
      extreme complexity of the proteomes present tremendous challenges. In this review
      we summarize recent advances in LC-MS-based proteomics profiling and its
      applications in clinical proteomics as well as discuss the major challenges
      associated with implementing these technologies for more effective candidate
      biomarker discovery. Developments in immunoaffinity depletion and various
      fractionation approaches in combination with substantial improvements in LC-MS
      platforms have enabled the plasma proteome to be profiled with considerably
      greater dynamic range of coverage, allowing many proteins at low ng/ml levels to
      be confidently identified. Despite these significant advances and efforts, major
      challenges associated with the dynamic range of measurements and extent of
      proteome coverage, confidence of peptide/protein identifications, quantitation
      accuracy, analysis throughput, and the robustness of present instrumentation must
      be addressed before a proteomics profiling platform suitable for efficient
      clinical applications can be routinely implemented.

PMID- 16887933
TI  - The concerted contribution of the S4-S5 linker and the S6 segment to the
      modulation of a Kv channel by 1-alkanols.
AB  - Gating of voltage-gated K(+) channels (K(v) channels) depends on the
      electromechanical coupling between the voltage sensor and activation gate. The
      main activation gate of K(v) channels involves the COOH-terminal section of the
      S6 segment (S6-b) and the S4-S5 linker at the intracellular mouth of the pore. In
      this study, we have expanded our earlier work to probe the concerted contribution
      of these regions to the putative amphipathic 1-alkanol site in the Shaw2 K(+)
      channel. In the S4-S5 linker, we found a direct energetic correlation between
      alpha-helical propensity and the inhibition of the Shaw2 channel by 1-butanol.
      Spectroscopic structural analyses of the S4-S5 linker supported this correlation.
      Furthermore, the analysis of chimeric Shaw2 and K(v)3.4 channels that exchanged
      their corresponding S4-S5 linkers showed that the potentiation induced by 1
      butanol depends on the combination of a single mutation in the S6 PVPV motif
      (PVAV) and the presence of the Shaw2 S4-S5 linker. Then, using tandem-heterodimer
      subunits, we determined that this potentiation also depends on the number of S4
      S5 linkers and PVAV mutations in the K(v) channel tetramer. Consistent with the
      critical contribution of the Shaw2 S4-S5 linker, the equivalent PVAV mutation in
      certain mammalian K(v) channels with divergent S4-S5 linkers conferred weak
      potentiation by 1-butanol. Overall, these results suggest that 1-alkanol action
      in Shaw2 channels depends on interactions involving the S4-S5 linker and the S6-b
      segment. Therefore, we propose that amphiphilic general anesthetic agents such as
      1-alkanols may modulate gating of the Shaw2 K(+) channel by an interaction with
      its activation gate.

PMID- 16887934
TI  - Hypoxia-inducible factor-1 (HIF-1).
AB  - Adaptation to low oxygen tension (hypoxia) in cells and tissues leads to the
      transcriptional induction of a series of genes that participate in angiogenesis,
      iron metabolism, glucose metabolism, and cell proliferation/survival. The primary
      factor mediating this response is the hypoxia-inducible factor-1 (HIF-1), an
      oxygen-sensitive transcriptional activator. HIF-1 consists of a constitutively
      expressed subunit HIF-1beta and an oxygen-regulated subunit HIF-1alpha (or its
      paralogs HIF-2alpha and HIF-3alpha). The stability and activity of the alpha
      subunit of HIF are regulated by its post-translational modifications such as
      hydroxylation, ubiquitination, acetylation, and phosphorylation. In normoxia,
      hydroxylation of two proline residues and acetylation of a lysine residue at the
      oxygen-dependent degradation domain (ODDD) of HIF-1alpha trigger its association
      with pVHL E3 ligase complex, leading to HIF-1alpha degradation via ubiquitin
      proteasome pathway. In hypoxia, the HIF-1alpha subunit becomes stable and
      interacts with coactivators such as cAMP response element-binding protein binding
      protein/p300 and regulates the expression of target genes. Overexpression of HIF
      1 has been found in various cancers, and targeting HIF-1 could represent a novel
      approach to cancer therapy.

PMID- 16887937
TI  - The 8th world conference.

PMID- 16887935
TI  - Overcoming trastuzumab resistance in HER2-overexpressing breast cancer cells by
      using a novel celecoxib-derived phosphoinositide-dependent kinase-1 inhibitor.
AB  - Although trastuzumab has been successfully used in patients with HER2
      overexpressing metastatic breast cancer, resistance is a common problem that
      ultimately culminates in treatment failure. In light of the importance of Akt
      signaling in trastuzumab's antitumor action, we hypothesized that concurrent
      inhibition of Akt could enhance trastuzumab sensitivity and moreover reverse the
      resistant phenotype in HER2-positive breast cancer cells. Based on our finding
      that celecoxib mediates antitumor effects through the inhibition of
      phosphoinositide-dependent kinase-1 (PDK-1)/Akt signaling independently of
      cyclooxygenase-2 (COX-2), we used celecoxib as a scaffold to develop a COX-2
      inactive PDK-1 inhibitor, 2-amino-N-[4-[5-(2-phenanthrenyl)-3-(trifluoromethyl)
      1H-pyrazol-1-yl]phenyl]-acetamide (OSU-03012). Here, we investigated the effect
      of OSU-03012 on trastuzumab-mediated apoptosis in four breast cancer cell lines
      with different HER2 expression and trastuzumab-resistance status, including MDA
      MB-231, BT474, SKBR3, and insulin-like growth factor-I receptor-overexpressing
      SKBR3 (SKBR3/IGF-IR). Effects of trastuzumab and OSU-03012, individually or in
      combination, on cell viability and changes in pertinent biomarkers including HER2
      expression, phosphorylation of Akt, p27(kip1), and the PDK-1 substrate p70(S6K)
      were assessed. OSU-03012 alone was able to trigger apoptosis in all cell lines
      with equal potency (IC(50) = 3-4 microM), suggesting no cross-resistance with
      trastuzumab. Medium dose-effect analysis indicates that OSU-03012 potentiated
      trastuzumab's antiproliferative effect in HER2-positive cells, especially in
      SKBR3/IGF-IR cells, through the down-regulation of PDK-1/Akt signaling. This
      synergy, however, was not observed in HER2-negative MDA-MB-231 cells. This
      combination treatment represents a novel strategy to increase the efficacy of
      trastuzumab and to overcome trastuzumab resistance in the treatment of HER2
      positive breast cancer.

PMID- 16887938
TI  - WHO's Plan of Action.

PMID- 16887936
TI  - Inhibition of in vivo glioma growth and invasion by peroxisome proliferator
      activated receptor gamma agonist treatment.
AB  - The peroxisome proliferator-activated receptor gamma (PPARgamma), a member of the
      nuclear hormone receptor family, represents a possible new target in glioma
      therapy. Because PPARgamma plays a crucial role in regulation of insulin
      sensitivity, synthetic agonists are already in clinical use for type II diabetes
      treatment. Beyond these metabolic effects, PPARgamma agonists exhibit
      antineoplastic effects. In this study, we investigated the antineoplastic effects
      of the PPARgamma agonist pioglitazone in glioma cells. Pioglitazone reduced
      cellular viability of rat, human, and PPARgamma-overexpressing glioma cells in
      vitro in a time- and concentration-dependent manner. No antineoplastic effects
      were induced by pioglitazone in glioma cells overexpressing a PPARgamma mutant.
      Furthermore, proliferation was reduced by pioglitazone, as measured by Ki-67
      immunoreactivity, in vitro. Continuous intracerebral infusion of pioglitazone
      into gliomas induced by intrastriatal injection of C6 cells reduced tumor volumes
      by 83%. Oral administration of pioglitazone reduced tumor volumes by 76.9%.
      Subsequent brain tissue analysis revealed induction of apoptotic cell death. Ki
      67 expression and BrdU incorporation revealed a reduction of proliferation in
      vivo. Reduced invasion of C6 cells and lower matrix metalloproteinase 9 levels in
      vivo indicate pioglitazone-mediated reduction of invasion. Together, these data
      indicate that pioglitazone may be of potential use in treatment of malignant
      gliomas.

PMID- 16887939
TI  - The International Society for Violence and Injury Prevention.

PMID- 16887940
TI  - When reviewers disagree.

PMID- 16887941
TI  - Incidence and lifetime costs of injuries in the United States.
AB  - BACKGROUND: Standardized methodologies for assessing economic burden of injury at
      the national or international level do not exist. OBJECTIVE: To measure national
      incidence, medical costs, and productivity losses of medically treated injuries
      using the most recent data available in the United States, as a case study for
      similarly developed countries undertaking economic burden analyses. METHOD: The
      authors combined several data sets to estimate the incidence of fatal and non
      fatal injuries in 2000. They computed unit medical and productivity costs and
      multiplied these costs by corresponding incidence estimates to yield total
      lifetime costs of injuries occurring in 2000. MAIN OUTCOME MEASURES: Incidence,
      medical costs, productivity losses, and total costs for injuries stratified by
      age group, sex, and mechanism. RESULTS: More than 50 million Americans
      experienced a medically treated injury in 2000, resulting in lifetime costs of
      406 billion dollars; 80 billion dollars for medical treatment and 326 billion
      dollars for lost productivity. Males had a 20% higher rate of injury than
      females. Injuries resulting from falls or being struck by/against an object
      accounted for more than 44% of injuries. The rate of medically treated injuries
      declined by 15% from 1985 to 2000 in the US. For those aged 0-44, the incidence
      rate of injuries declined by more than 20%; while persons aged 75 and older
      experienced a 20% increase. CONCLUSIONS: These national burden estimates provide
      unequivocal evidence of the large health and financial burden of injuries. This
      study can serve as a template for other countries or be used in intercountry
      comparisons.

PMID- 16887942
TI  - Police deaths in New York and London during the twentieth century.
AB  - OBJECTIVES: To describe the incidences and causes of occupational police deaths
      in New York City in the United States and Greater London in the United Kingdom
      during the twentieth century. To assess the relation between overall societal
      violence and violence directed toward police officers in these metropolitan
      areas. DESIGN AND SETTING: Ecological study of New York and London from 1900
      through 1999. MAIN OUTCOME MEASURES: Intentional and unintentional occupational
      police mortality rates for New York and London were estimated for each decade.
      The general population homicide rates of both New York and London were assessed
      for their correlation with their respective intentional occupational police
      mortality rates. RESULTS: During the 20th century, 585 police officers in New
      York and 160 police officers in London died while participating in law
      enforcement activities. New York had markedly greater intentional police
      mortality rates compared to London throughout most of the 20th century, but these
      differences decreased significantly by the end of the century. Intentional
      gunshot wounds comprised 290 police deaths in New York, but only 14 police deaths
      in London. In New York, gun shot wounds (both intentional and unintentional)
      accounted for more occupational police deaths (51.6%) than did all other injury
      mechanisms combined. In London, motor vehicle collision was the most common cause
      (47.5%) of occupational police death. There were no apparent correlations between
      the general population homicide rates and intentional police mortality rates in
      either New York (r(2) = 0.05, 95% CI -0.77 to 0.81) or London (r(2) = 0.34, 95%
      CI -0.61 to 0.89). CONCLUSIONS: During the 20th century, both intentional and
      unintentional occupational police mortality rates were significantly greater in
      New York compared to London. These differences are likely from several
      socioeconomic, cultural, and occupational factors. The declines in police deaths
      in New York during the latter part of the 20th century indicate that at least
      some measures taken by the New York Police Department have been successful at
      significantly reducing the incidence of both intentional and unintentional police
      deaths.

PMID- 16887943
TI  - Effects of undercover police stings of gun dealers on the supply of new guns to
      criminals.
AB  - OBJECTIVE: To assess the effects of undercover police stings and lawsuits against
      gun dealers suspected of facilitating illegal gun sales in three US cities
      (Chicago, Detroit, Gary) on the flow of new firearms to criminals. METHODS: An
      interrupted time series design and negative binomial regression analyses were
      used to test for temporal change in the recovery of guns used in crimes within
      one year of retail sale in both intervention and comparison cities. RESULTS: The
      stings were associated with an abrupt 46.4% reduction in the flow of new guns to
      criminals in Chicago (95% confidence interval, -58.6% to -30.5%), and with a
      gradual reduction in new crime guns recovered in Detroit. There was no
      significant change associated with the stings in Gary, and no change in
      comparison cities that was coincident with the stings in Chicago and Detroit.
      CONCLUSIONS: The announcement of police stings and lawsuits against suspect gun
      dealers appeared to have reduced the supply of new guns to criminals in Chicago
      significantly, and may have contributed to beneficial effects in Detroit. Given
      the important role that gun stores play in supplying guns to criminals in the US,
      further efforts of this type are warranted and should be evaluated.

PMID- 16887944
TI  - Economic disparity in bicycle helmet use by children six years after the
      introduction of legislation.
AB  - BACKGROUND: Studies evaluating the effectiveness of bicycle helmet legislation
      often focus on short term outcomes. The long term effect of helmet legislation on
      bicycle helmet use is unknown. OBJECTIVE: To examine bicycle helmet use by
      children six years after the introduction of the law, and the influence of area
      level family income on helmet use. METHODS: The East York (Toronto) health
      district (population 107,822) was divided into income areas (designated as low,
      mid, and high) based on census tract data from Statistics Canada. Child cyclists
      were observed at 111 preselected sites (schools, parks, residential streets, and
      major intersections) from April to October in the years 1995-1997, 1999, and
      2001. The frequency of helmet use was determined by year, income area, location,
      and sex. Stratified analysis was used to quantify the relation between income
      area and helmet use, after controlling for sex and bicycling location. RESULTS:
      Bicycle helmet use in the study population increased from a pre-legislation level
      of 45% in 1995 to 68% in 1997, then decreased to 46% by 2001. Helmet use
      increased in all three income areas from 1995 to 1997, and remained above pre
      legislation rates in high income areas (85% in 2001). In 2001, six years post
      legislation, the proportion of helmeted cyclists in mid and low income areas had
      returned to pre-legislation levels (50% and 33%, respectively). After adjusting
      for sex and location, children riding in high income areas were significantly
      more likely to ride helmeted than children in low income areas across all years
      (relative risk = 3.4 (95% confidence interval, 2.7 to 4.3)). CONCLUSION: Over the
      long term, the effectiveness of bicycle helmet legislation varies by income area.
      Alternative, concurrent, or ongoing strategies may be necessary to sustain
      bicycle helmet use among children in mid and low income areas following
      legislation.

PMID- 16887945
TI  - Blurring the distinctions between on and off the job injuries: similarities and
      differences in circumstances.
AB  - OBJECTIVES: To compare the causes of non-fatal work and non-work injuries and the
      places or environments where they occur. It has been suggested that many injuries
      may have similar etiologies on and off the job and thus involve some common
      prevention strategies. However lack of comparable data on work relatedness has
      prevented testing this proposition. METHODS: The National Health Interview Survey
      (NHIS) now collects information on the cause, location, and work relatedness of
      all medically attended injuries. National US estimates of non-fatal work and non
      work injuries were compared by cause and place/location for working age adults
      (18-64 years). RESULTS: Overall 28.6% of injuries to working age adults were work
      related (37.5% among employed people). The causes and locations of many work and
      non-work injuries were similar. Falls, overexertion, and struck/caught by were
      leading causes for work and non-work injuries. Motor vehicle injuries were less
      likely to be work related (3.4% at work v 19.5% non-work) and overexertion
      injuries more likely to be work related (27.1% v 13.8%). Assaults were less than
      1% of work injuries and 1.8% of non-work injuries. Both work and non-work
      injuries occurred in every location examined-including the home where 3.5% of
      injuries were work related. CONCLUSIONS: Work and non-work injuries share many
      similarities suggesting opportunities to broaden injury prevention programs
      commonly restricted to one setting or the other. Comprehensive efforts to prevent
      both non-work and work injuries may result in considerable cost savings not only
      to society but also directly to employers, who incur much of the associated
      costs.

PMID- 16887946
TI  - The impact of driver distraction on road safety: results from a representative
      survey in two Australian states.
AB  - OBJECTIVE: To quantify the prevalence and effects of distracting activities while
      driving. DESIGN: Cross sectional driver survey. SETTING: New South Wales and
      Western Australia, Australia. PARTICIPANTS: 1347 licensed drivers aged between 18
      and 65 years. Data were weighted to reflect the corresponding driving population.
      MAIN OUTCOME MEASURES: Prevalence of distracting activities while driving;
      perceived risks and adverse outcomes due to distractions. RESULTS: The most
      common distracting activities during the most recent driving trip were lack of
      concentration (weighted percentage (standard error, SE) 71.8% (1.4%) of drivers);
      adjusting in-vehicle equipment (68.7% (1.5%)); outside people, objects or events
      (57.8% (1.6%)); and talking to passengers (39.8% (1.6%)). On average, a driver
      engaged in a distracting activity once every six minutes. One in five crashes
      (21%) during the last three years, involving one in 20 drivers (5.0% (0.7%)), was
      attributed to driver distraction based on self-report. In the population under
      study, this equated to 242,188 (SE 34,417) drivers. Younger drivers (18-30 years)
      were significantly more likely to report distracting activities, to perceive
      distracting activities as less dangerous, and to have crashed as a result.
      CONCLUSIONS: Distracting activities while driving are common and can result in
      driving errors. Driver distraction is an important cause of crashes. Further
      research is needed to estimate the risk conferred by different distracting
      activities and the circumstances during which activities pose greatest risk.
      These results suggest that a strategy to minimize distracting activities while
      driving, with a focus on young drivers, is indicated.

PMID- 16887948
TI  - The properties of the International Classification of the External Cause of
      Injury when used as an instrument for injury prevention research.
AB  - OBJECTIVE: To demonstrate properties of the International Classification of the
      External Cause of Injury (ICECI) as a tool for use in injury prevention research.
      METHODS: The Childhood Injury Prevention Study (CHIPS) is a prospective
      longitudinal follow up study of a cohort of 871 children 5-12 years of age, with
      a nested case crossover component. The ICECI is the latest tool in the
      International Classification of Diseases (ICD) family and has been designed to
      improve the precision of coding injury events. The details of all injury events
      recorded in the study, as well as all measured injury related exposures, were
      coded using the ICECI. This paper reports a substudy on the utility and
      practicability of using the ICECI in the CHIPS to record exposures. Interrater
      reliability was quantified for a sample of injured participants using the Kappa
      statistic to measure concordance between codes independently coded by two
      research staff. RESULTS: There were 767 diaries collected at baseline and event
      details from 563 injuries and exposure details from injury crossover periods.
      There were no event, location, or activity details which could not be coded using
      the ICECI. Kappa statistics for concordance between raters within each of the
      dimensions ranged from 0.31 to 0.93 for the injury events and 0.94 and 0.97 for
      activity and location in the control periods. DISCUSSION: This study represents
      the first detailed account of the properties of the ICECI revealed by its use in
      a primary analytic epidemiological study of injury prevention. The results of
      this study provide considerable support for the ICECI and its further use.

PMID- 16887947
TI  - Lower rates of emergency department injury visits among Latino children in the
      USA: no association with health insurance.
AB  - BACKGROUND AND OBJECTIVE: Latino children have lower rates of injury visits to
      emergency departments (EDs) than non-Latino white and African American children.
      This study tests the hypothesis that this difference reflects health insurance
      status. DESIGN: Secondary analysis. Patients/ SETTING: Children under 19 years of
      age visiting EDs in the USA, sampled in the National Hospital Ambulatory Medical
      Care Survey of EDs (NHAMCS-ED) from 1997 to 2001. MAIN OUTCOME MEASURES: Rates of
      ED injury visits; ED injury visit rates by race/ethnicity stratified by health
      insurance and adjusted for other covariates; subtypes of injury visits; and
      procedures and hospital admissions by race/ethnicity. RESULTS: Injuries accounted
      for >56 million, or 40.5%, of total ED visits among pediatric patients. Injury
      visits occurred at lower rates for Latino children (9.9 per 100 person years)
      than non-Latino white and African American children (16.2 and 18.3,
      respectively), although total ED visit rates were similar. Regardless of health
      insurance status, Latino children had lower rates of injury visits than non
      Latino white and African American children. Latino children had lower rates of
      the three major subtypes of injury visits (sports, accidental falls, struck
      by/between objects). Latino children had similar rates of procedures and hospital
      admissions to non-Latino white children. CONCLUSIONS: Irrespective of their
      insurance status, Latino children have lower rates of ED injury visits in the USA
      than non-Latino white children. Possible reasons for this difference include
      different healthcare seeking behavior or different injury patterns by
      race/ethnicity, but not differences in health insurance status or barriers to
      accessing ED care.

PMID- 16887949
TI  - International survey of seat belt use exemptions.
AB  - BACKGROUND: Substantial evidence of seatbelt efficacy has been shown by several
      studies, and it is widely recommended that motor vehicle occupants use properly
      fitted seat belts. However, some (but a heretofore unknown number of) countries
      with national seat belt laws permit various exemptions which may lower use rates.
      The aim of this study was to survey the variety of exemptions to national seat
      belt laws. METHODS: This investigation relied on identifying respondents from
      national traffic safety agencies, other governmental and non-governmental
      organizations, Internet searches, personal contacts, and other sources.
      Questionnaires were deployed through a web based survey supplemented by email and
      postal versions. RESULTS: Responses were received from 30 countries of which 28
      (93.7%) had a national seat belt law. About two thirds (63.7%) of the 28 national
      laws applied to both front and back seat passengers. The leading exemption types
      included vehicles made before a certain year (n = 13), antique vehicles (n = 12),
      military vehicles (n = 11), buses (n = 9), and emergency vehicles (n = 8). Most
      responding countries reported one or more specific categories of individuals as
      exempt including those with medical exemptions (n = 20), taxi drivers (n = 11),
      police (n = 9), emergency medical personnel (n = 8), physically disabled people
      (n = 6), and pregnant women (n = 6). Out of 26 responses to the question
      regarding current level of enforcement, 42.3% felt enforcement was "very good or
      good" and 57.7% characterized it as "fair or poor". CONCLUSIONS: This study
      represents one of the largest international traffic law surveys reported. Most
      national seatbelt laws offer perilous exemptions to a broad array of vehicle
      types and road user groups. These findings, coupled with concern over the level
      of enforcement in the majority of countries surveyed, suggest that international
      road safety efforts have a long way to go to improve coverage and enforcement of
      national seat belt laws.

PMID- 16887950
TI  - Bicycle helmet prevalence two years after the introduction of mandatory use
      legislation for under 18 year olds in Alberta, Canada.
AB  - OBJECTIVE: To determine changes in helmet use in cyclists following the
      introduction of a bicycle helmet law for children under age 18. METHODS: Cyclists
      were observed by two independent observers from July to August 2004 (post
      legislation) in Edmonton, Alberta. The data were compared with a similar survey
      completed at the same locations and days in July to August 2000 (pre
      legislation). Data were collected for 271 cyclists in 2004 and 699 cyclists in
      2000. RESULTS: The overall prevalence of helmet use increased from 43% (95% CI 39
      to 47%) in 2000 to 53% (95% CI 47 to 59%) in 2004. Helmet use increased in those
      under 18, but did not change in those 18 and older. In the cluster adjusted
      multivariate Poisson regression model, the prevalence of helmet use significantly
      increased for those under age 18 (adjusted prevalence ratio (APR) 3.69, 95% CI
      2.65 to 5.14), but not for those 18 years and older (APR 1.17, 95% CI 0.95 to
      1.43). CONCLUSION: Extension of legislation to all age groups should be
      considered.

PMID- 16887951
TI  - Motorcycle injuries in a developing country and the vulnerability of riders,
      passengers, and pedestrians.
AB  - At a Nigerian university hospital, none of the motorcyclists who presented over a
      12 month period had been wearing a helmet, and of the eight patients who died,
      seven had head injuries. Of the five collision types described, the rate of
      motorcycle-other vehicle collisions was highest at 40.6%, while the motorcycle
      pedestrian rate was 23.4%. Measures to prevent these collisions might reduce
      overall crashes by 64%; in addition, helmet law should be enforced.

PMID- 16887953
TI  - The logic of comparing international terrorism with other causes of injury.

PMID- 16887952
TI  - Audit of an intervention to decrease cycle related head injuries in primary
      school children.

PMID- 16887954
TI  - Alcohol related harm.

PMID- 16887956
TI  - Comment on "CCR7 is critically important for migration of dendritic cells in
      intestinal lamina propria to mesenteric lymph nodes".

PMID- 16887955
TI  - Flagellasialin: a novel sulfated alpha2,9-linked polysialic acid glycoprotein of
      sea urchin sperm flagella.
AB  - A novel alpha2,9-linked polysialic acid (polySia)-containing glycoprotein of sea
      urchin sperm flagella was identified and named "flagellasialin." Flagellasialin
      from Hemicentrotus pulcherrimus shows a diverse relative molecular mass on sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of 40-80 kDa.
      Flagellasialin is a 96-amino acid, threonine-rich, heavily O-glycosylated (80-90%
      by weight) glycoprotein with a single transmembrane segment at its C-terminus and
      no apparent cytosolic domain. Of 12 extracellular Thr residues, eight are O
      glycosylated and three are nonglycosylated. Flagellasialin is highly expressed in
      the testis but cannot be detected in the ovary. The amino acid sequences of
      flagellasialin from three sea urchin species (H. pulcherrimus, Strongylocentrotus
      purpuratus, and Strongylocentrotus franciscanus) are identical, but some species
      differences exist in the three core glycan structures to which the sulfated
      alpha2,9-linked polyNeu5Ac chain is linked. Finally, the treatment of sperm with
      a specific antibody against the alpha2,9-linked polyNeu5Ac structure results in
      the elevation of intracellular Ca(2+) and inhibition of sperm motility and
      fertilization, implicating flagellasialin as a regulator of these critical
      processes.

PMID- 16887957
TI  - Comment on "Cutting edge: anti-CD25 monoclonal antibody injection results in the
      functional inactivation, not depletion, of CD4+CD25+ T regulatory cells".

PMID- 16887958
TI  - Comment on "Cutting edge: anti-CD25 monoclonal antibody injection results in the
      functional inactivation, not depletion, of CD4+CD25+ T regulatory cells".

PMID- 16887959
TI  - Comment on "Duration and intensity of NF-kappa B activity determine the severity
      of endotoxin-induced acute lung injury".

PMID- 16887960
TI  - CCR5 in T cell-mediated liver diseases: what's going on?
AB  - The chemokine receptor CCR5 came into worldwide prominence a decade ago when it
      was identified as one of the major coreceptors for HIV infectivity. However,
      subsequent studies suggested an important modulatory role for CCR5 in the
      inflammatory response. Specifically, CCR5 has been reported to directly regulate
      T cell function in autoimmune diseases, including multiple sclerosis, rheumatoid
      arthritis, and type 1 diabetes. Moreover, T cell-mediated immune responses are
      proposed to be critical in the pathogenesis of autoimmune and viral liver
      diseases, and recent clinical and experimental studies have also implicated CCR5
      in the pathogenesis of autoimmune and viral liver diseases. Therefore, in this
      brief review, we highlight the evidence that supports an important role of CCR5
      in the pathophysiology of T cell-mediated liver diseases with specific emphasis
      on autoimmune and viral liver diseases.

PMID- 16887961
TI  - Cutting edge: dexamethasone negatively regulates Syk in mast cells by up
      regulating SRC-like adaptor protein.
AB  - We have identified Src-like adaptor protein (SLAP) as one of several
      dexamethasone-inducible inhibitory regulators in mast cells. SLAP is a known
      inhibitor of T cell signaling and interacts with the tyrosine kinase, Zap70.
      Exposure of RBL-2H3 mast cells to dexamethasone markedly increased expression of
      SLAP. Cells so exposed or made to overexpress SLAP exhibited reduced Ag
      stimulated phosphorylation of Syk (a cognate of Zap70), linker for activation of
      T cells, phospholipase Cgamma, and ERK. Ca(2+) mobilization, Ca(2+)-dependent
      degranulation, and ERK-dependent release of arachidonic acid were suppressed as
      well. Small interfering RNA directed against SLAP blocked the induction of SLAP
      and reversed the inhibitory effects of dexamethasone on phosphorylation of Syk,
      linker for activation of T cells, and phospholipase Cgamma, but not downstream
      events, which are likely suppressed by up-regulation of downstream of tyrosine
      kinase-1 and MAPK phosphatase-1. The induction of these inhibitory regulators may
      contribute to the immunosuppressive activity of dexamethasone in mast cells.

PMID- 16887962
TI  - Cutting edge: inhibition of TLR and FcR responses in macrophages by triggering
      receptor expressed on myeloid cells (TREM)-2 and DAP12.
AB  - DAP12 is an ITAM-containing adapter that associates with receptors in myeloid and
      NK cells. DAP12-associated receptors can give activation signals leading to
      cytokine production; however, in some situations, DAP12 inhibits cytokine
      production stimulated through TLRs and FcRs. Here we show that Triggering
      Receptor Expressed on Myeloid cells (TREM)-2 is responsible for the DAP12
      mediated inhibition in mouse macrophages. A chimeric receptor composed of the
      extracellular domain of TREM-2 and the cytoplasmic domain of DAP12 inhibited the
      TLR- and FcR-induced TNF production of DAP12-deficient macrophages, whereas a
      TREM-1 chimera did not. In wild-type macrophages, TREM-2 knockdown increased TLR
      induced TNF production. A TREM-2 Fc fusion protein bound to macrophages,
      indicating that macrophages express a TREM-2 ligand. Thus, the interaction of
      TREM-2 and its ligand results in an inhibitory signal that can reduce the
      inflammatory response.

PMID- 16887963
TI  - Cutting edge: Epstein-Barr virus transactivates the HERV-K18 superantigen by
      docking to the human complement receptor 2 (CD21) on primary B cells.
AB  - EBV, a ubiquitous human herpesvirus, is the causative agent of infectious
      mononucleosis and is associated with many carcinomas. We have previously shown
      that the EBV latent genes LMP-1 and LMP-2A (for latent membrane proteins 1 and
      2A), transactivate a human endogenous retrovirus (HERV), HERV-K18, in infected B
      lymphocytes. The envelope (Env) protein of HERV-K18 encodes a superantigen that
      strongly stimulates a large number of T cells. In this study we report that HERV
      K18 env is transactivated even earlier in the infection process, before the
      establishment of latency; namely, we found that EBV, through its interaction with
      its cellular receptor CD21, induces the HERV-K18 env gene in resting B
      lymphocytes. This transactivation is direct and immediate, as up-regulation of
      transcripts can be detected within 30 min after EBV exposure. Thus, EBV binding
      to human CD21 on resting B cells triggers the expression of an endogenous
      superantigen. The biological significance of this superantigen expression for the
      EBV life cycle is discussed.

PMID- 16887964
TI  - 1-Methyl-tryptophan can interfere with TLR signaling in dendritic cells
      independently of IDO activity.
AB  - The compound 1-methyl-tryptophan (1-MT) is a competitive inhibitor of IDO that
      can break tolerance and induce fetus, graft, and tumor rejection. Because of its
      broad effect on immune-related mechanisms, the direct action of 1-MT on human
      monocyte-derived dendritic cells (DC) was analyzed. It is shown here that the
      effect of 1-MT on DC is dependent on the maturation pathway. Although 1-MT had no
      effect on DC stimulated by the TLR3 ligand poly(I:C), it strongly enhanced the
      Th1 profile of DC stimulated with TLR2/1 or TLR2/6 ligands. Drastic changes in
      the function of DC stimulated by the TLR4 ligand LPS were induced by 1-MT. These
      cells could still activate allogeneic and syngeneic T cells but stimulation
      yielded T cells secreting IL-5 and IL-13 rather than IFN-gamma. This action of 1
      MT correlated with an increased phosphorylation of p38 and ERK MAPKs and
      sustained activation of the transcription factor c-Fos. Inhibiting p38 and ERK
      phosphorylation with synthetic inhibitors blocked the effect of 1-MT on LPS
      stimulated DC. Thus, 1-MT can modulate DC function depending on the maturation
      signal and independently of its action on IDO. This is consistent with previous
      observations and will help further understanding the mechanisms of DC
      polarization.

PMID- 16887965
TI  - Characterization of (4-hydroxy-3-nitrophenyl)acetyl (NP)-specific germinal center
      B cells and antigen-binding B220- cells after primary NP challenge in mice.
AB  - Previous studies examining the primary germinal center (GC) response to SRBC in
      mice demonstrated a steady ratio of IgM(+) to isotype-switched GC B cells and a
      persistent population of GC B cells with a founder phenotype. These
      characteristics held true at the inductive, plateau, and dissociative phases of
      the GC response, suggesting a steady-state environment. To test whether these
      characteristics apply to the primary response of other T cell-dependent Ags, the
      present study examined the GC response after challenge with (4-hydroxy-3
      nitrophenyl)acetyl (NP) in C57BL/6 mice. Multiparameter flow cytometric analysis
      was used to assess the phenotype of splenic NP-reactive cells at multiple time
      points after immunization. Results of these studies demonstrated the
      characteristics of the SRBC-induced GC reaction to be fully maintained in the NP
      response. In particular, there was a steady ratio of nonswitched to switched B
      cells, with the majority of NP-reactive GC B cells displaying IgM. In addition, a
      substantial frequency of B220(-) NP-binding cells was observed in the spleen at
      later time points after NP challenge. Although these cells were IgE(+), they were
      found to express both kappa and lambda L chains and display the high-affinity IgE
      Fc (FcepsilonRI) receptor, suggesting that this population is not of B cell
      origin. Adoptive transfer studies further demonstrated the B220(-) NP-binding
      subset to be derived from the myeloid lineage.

PMID- 16887966
TI  - Mesenchymal stem cells inhibit generation and function of both CD34+-derived and
      monocyte-derived dendritic cells.
AB  - Mesenchymal stem cells (MSCs) are not only able to evade the immune system, but
      they have also been demonstrated to exert profound immunosuppressive properties
      on T cell proliferation. However, their effect on the initiators of the immune
      response, the dendritic cells (DCs), are relatively unknown. In the present
      study, the effects of human MSCs on the differentiation and function of both
      CD34+ -derived DCs and monocyte-derived DCs were investigated. The presence of
      MSCs during differentiation blocked the differentiation of CD14+CD1a- precursors
      into dermal/interstitial DCs, without affecting the generation of CD1a+
      Langerhans cells. In line with these observations, MSCs also completely prevented
      the generation of immature DCs from monocytes. The inhibitory effect of MSCs on
      DC differentiation was dose dependent and resulted in both phenotypical and
      functional modifications, as demonstrated by a reduced expression of
      costimulatory molecules and hampered capacity to stimulate naive T cell
      proliferation. The inhibitory effect of MSCs was mediated via soluble factors.
      Taken together, these data demonstrate that MSCs, next to the antiproliferative
      effect on T cells, have a profound inhibitory effect on the generation and
      function of both CD34+ -derived and monocyte-derived DCs, indicating that MSCs
      are able to modulate immune responses at multiple levels.

PMID- 16887967
TI  - TLR7 ligands induce higher IFN-alpha production in females.
AB  - IFN-alpha exercises multiple immune modulatory and antiviral activities and has
      been suggested to play a critical role in the pathogenesis of systemic lupus
      erythematosus (SLE). Plasmacytoid dendritic cells (pDCs) release IFN-alpha upon
      TLR7 and TLR9 ligation. With respect to the nine times higher incidence of SLE in
      women and the clinical use of synthetic TLR ligands as novel immune adjuvants, we
      analyzed IFN-alpha and TNF-alpha production in healthy human individuals. Blood
      samples were incubated with synthetic TLR7 and TLR9 ligands. In three independent
      groups (n(1) = 120, n(2) = 101, and n(3) = 123), analysis revealed a capacity of
      female PBLs to produce significantly higher IFN-alpha levels after TLR7
      stimulation (p(1) < 0.0000001, p(2) < 0.0000001, and p(3) < 0.0001) compared with
      male PBLs. In contrast, no sex differences were evident after TLR9 stimulation.
      TNF-alpha production after TLR7 stimulation and also total pDC numbers were not
      different between females and males. X-inactivation escape of the TLR7 gene was
      investigated in monoclonal B cell lines and, independently, in pDCs after cell
      sorting and single-cell picking, indicating regular silencing of one TLR7 allele
      in females. Additionally, exogenous 17beta-estrogen and estrogen receptor
      antagonism did not indicate a significant role on TLR7-induced IFN-alpha
      production. Our data reveal for the first time a profound sex-dependent pathway
      of TLR7-induced IFN-alpha with higher production in females. These findings may
      explain the higher prevalence of SLE in females and the reported decreased
      therapeutic efficacy of synthetic TLR7 ligands in male individuals.

PMID- 16887968
TI  - Endogenous myelin basic protein is presented in the periphery by both dendritic
      cells and resting B cells with different functional consequences.
AB  - Multiple sclerosis is an inflammatory disease believed to be triggered by
      erroneous activation of self-reactive T cells specific for myelin proteins such
      as myelin basic protein (MBP). Inflammation is limited to the CNS, suggesting
      that the myelin-specific T cells encounter their Ags only after they cross the
      blood-brain barrier. However, our previous studies in mice showed that MBP
      epitopes are constitutively presented in lymphoid tissues. Here we identified
      which APCs in lymph nodes present endogenous MBP epitopes and determined the
      functional consequences of this presentation for both naive and activated MBP
      specific T cells. Both CD8alpha+ and CD8alpha- dendritic cells were potent
      stimulators of proliferation for both naive and previously activated/memory MBP
      specific T cells. Surprisingly, resting B cells also presented endogenous MBP
      that was acquired using a BCR-independent mechanism. Interaction with resting B
      cells triggered proliferation of both naive and activated MBP-specific T cells.
      Activated/memory MBP-specific T cells proliferating in response to resting B
      cells presenting endogenous MBP did not produce cytokines and became more
      refractory to subsequent stimulation. Interestingly, cytokine production by
      activated/memory T cells was triggered by resting B cells if the number of MBP
      epitopes presented was increased by adding exogenous MBP peptide. These results
      suggest that activated MBP-specific T cells may become less pathogenic in vivo
      following encounter with resting B cells presenting steady-state levels of
      endogenous MBP but can expand and remain pathogenic if the amount of MBP
      presented by B cells is increased, which could occur during chronic demyelinating
      disease.

PMID- 16887969
TI  - RUNX3 negatively regulates CD36 expression in myeloid cell lines.
AB  - CD36 is a member of the scavenger receptor type B family implicated in the
      binding of lipoproteins, phosphatidylserine, thrombospondin-1, and the uptake of
      long-chain fatty acids. On mononuclear phagocytes, recognition of apoptotic cells
      by CD36 contributes to peripheral tolerance and prevention of autoimmunity by
      impairing dendritic cell (DC) maturation. Besides, CD36 acts as a coreceptor with
      TLR2/6 for sensing microbial diacylglycerides, and its deficiency leads to
      increased susceptibility to Staphylococcus aureus infections. The RUNX3
      transcription factor participates in reprogramming DC transcription after
      pathogen recognition, and its defective expression leads to abnormally
      accelerated DC maturation. We present evidence that CD36 expression is negatively
      regulated by the RUNX3 transcription factor during myeloid cell differentiation
      and activation. In molecular terms, RUNX3 impairs the activity of the proximal
      regulatory region of the CD36 gene in myeloid cells through in vitro recognition
      of two functional RUNX-binding elements. Moreover, RUNX3 occupies the CD36 gene
      proximal regulatory region in vivo, and its overexpression in myeloid cells
      results in drastically diminished CD36 expression. The down-regulation of CD36
      expression by RUNX3 implies that this transcription factor could impair harmful
      autoimmune responses by contributing to the loss of pathogen- and apoptotic cell
      recognition capabilities by mature DCs.

PMID- 16887970
TI  - Modulation of monocyte function by activated protein C, a natural anticoagulant.
AB  - Activated protein C is the first effective biological therapy for the treatment
      of severe sepsis. Although activated protein C is well established as a
      physiological anticoagulant, emerging data suggest that it also exerts anti
      inflammatory and antiapoptotic effects. In this study, we investigated the
      ability of activated protein C to modulate monocyte apoptosis, inflammation,
      phagocytosis, and adhesion. Using the immortalized human monocytic cell line THP
      1, we demonstrated that activated protein C inhibited camptothecin-induced
      apoptosis in a dose-dependent manner. The antiapoptotic effect of activated
      protein C requires its serine protease domain and is dependent on the endothelial
      cell protein C receptor and protease-activated receptor-1. In primary blood
      monocytes from healthy individuals, activated protein C inhibited spontaneous
      apoptosis. With respect to inflammation, activated protein C inhibited the
      production of TNF, IL-1beta, IL-6, and IL-8 by LPS-stimulated THP-1 cells.
      Activated protein C did not influence the phagocytic internalization of Gram
      negative and Gram-positive bioparticles by THP-1 cells or by primary blood
      monocytes. Activated protein C also did not affect the expression of adhesion
      molecules by LPS-stimulated blood monocytes nor the ability of monocytes to
      adhere to LPS-stimulated endothelial cells. We hypothesize that the protective
      effect of activated protein C in sepsis reflects, in part, its ability to prolong
      monocyte survival in a manner that selectively inhibits inflammatory cytokine
      production while maintaining phagocytosis and adherence capabilities, thereby
      promoting antimicrobial properties while limiting tissue damage.

PMID- 16887972
TI  - Type 2 cytotoxic T lymphocytes modulate the activity of dendritic cells toward
      type 2 immune responses.
AB  - Activated CD8+ T cells can differentiate into type 1 (Tc1) cells, producing
      mainly IFN-gamma, and type 2 (Tc2) cells, producing mostly IL-4, IL-5, and IL-10.
      Tc1 cells are potent CTL involved in the defense against intracellular pathogens
      and cancer cells. The role of Tc2 cells in the immune response is largely
      unknown, although their presence in chronic infections, cancer, and autoimmune
      diseases is associated with disease severity and progression. Here, we show that
      mouse Tc2 cells modify, through a cell-to-cell contact mechanism, the function of
      bone marrow-derived dendritic cells (DC). Indeed, Tc2-conditioned DC displayed a
      reduced expression of MHC class II and costimulatory molecules, produced IL-10
      instead of IL-12, and favored the differentiation of both naive CD4+ and CD8+ T
      cells toward type 2 cells in the absence of added polarizing cytokines. The novel
      function for Tc2 cells suggests a type 2 loop in which Tc2 cells modify DC
      function and favor differentiation of naive T cells to type 2 cells. The type 2
      loop may at least in part explain the unexpected high frequency of type 2 cells
      during a chronic exposure to the Ag.

PMID- 16887971
TI  - The role of structurally conserved class I MHC in tumor rejection: contribution
      of the Q8 locus.
AB  - The mouse multimember family of Qa-2 oligomorphic class I MHC genes is
      continuously undergoing duplications and deletions that alter the number of the
      two "prototype" Qa-2 sequences, Q8 and Q9. The frequent recombination events
      within the Q region lead to strain-specific modulation of the cumulative Qa-2
      expression levels. Q9 protects C57BL/6 hosts from multiple disparate tumors and
      functions as a major CTL restriction element for shared tumor-associated Ags. We
      have now analyzed functional and structural properties of Q8, a class I MHC that
      differs significantly from Q9 in the peptide-binding, CTL-interacting alpha(1)
      and alpha(2) regions. Unexpectedly, we find that the extracellular domains of Q8
      and Q9 act similarly during primary and secondary rejection of tumors, are
      recognized by cross-reactive antitumor CTL, have overlapping peptide-binding
      motifs, and are both assembled via the transporter associated with the Ag
      processing pathway. These findings suggest that shared Ag-presenting functions of
      the "odd" and "even" Qa-2 loci may contribute to the selective pressures shaping
      the haplotype-dependent quantitative variation of Qa-2 protein expression.

PMID- 16887973
TI  - Screening and identification of severe acute respiratory syndrome-associated
      coronavirus-specific CTL epitopes.
AB  - Severe acute respiratory syndrome (SARS) is a highly contagious and life
      threatening disease that emerged in China in November 2002. A novel SARS
      associated coronavirus was identified as its principal etiologic agent; however,
      the immunopathogenesis of SARS and the role of special CTLs in virus clearance
      are still largely uncharacterized. In this study, potential HLA-A*0201-restricted
      spike (S) and nucleocapsid protein-derived peptides were selected from an online
      database and screened for potential CTL epitopes by in vitro refolding and T2
      cell-stabilization assays. The antigenicity of nine peptides which could refold
      with HLA-A*0201 molecules was assessed with an IFN-gamma ELISPOT assay to
      determine the capacity to stimulate CTLs from PBMCs of HLA-A2(+) SARS-recovered
      donors. A novel HLA-A*0201-restricted decameric epitope P15 (S411-420,
      KLPDDFMGCV) derived from the S protein was identified and found to localize
      within the angiotensin-converting enzyme 2 receptor-binding region of the S1
      domain. P15 could significantly enhance the expression of HLA-A*0201 molecules on
      the T2 cell surface, stimulate IFN-gamma-producing CTLs from the PBMCs of former
      SARS patients, and induce specific CTLs from P15-immunized HLA-A2.1 transgenic
      mice in vivo. Furthermore, significant P15-specific CTLs were induced from HLA
      A2.1-transgenic mice immunized by a DNA vaccine encoding the S protein;
      suggesting that P15 was a naturally processed epitope. Thus, P15 may be a novel
      SARS-associated coronavirus-specific CTL epitope and a potential target for
      characterization of virus control mechanisms and evaluation of candidate SARS
      vaccines.

PMID- 16887974
TI  - Porcine UL16-binding protein 1 expressed on the surface of endothelial cells
      triggers human NK cytotoxicity through NKG2D.
AB  - Cellular rejection mechanisms, including NK cells, remain a hurdle for successful
      pig-to-human xenotransplantation. Human anti-pig NK cytotoxicity depends on the
      activating receptor NKG2D. Porcine UL16-binding protein 1 (pULBP1) and porcine
      MHC class I chain-related protein 2 (pMIC2) are homologues of the human NKG2D
      ligands ULBP 1-4 and MICA and B, respectively. Although transcribed in porcine
      endothelial cells (pEC), it is not known whether pULBP1 and pMIC2 act as
      functional ligands for human NKG2D. In this study, surface protein expression of
      pULBP1 was demonstrated by flow cytometry using a novel pULBP1-specific
      polyclonal Ab and by cellular ELISA using NKG2D-Fc fusion protein. Reciprocally,
      pULBP1-Fc bound to primary human NK cells, whereas pMIC2-Fc did not. Transient
      and stable down-regulation of pULBP1 mRNA in pEC using short-interfering RNA
      oligonucleotide duplexes and short hairpin RNA, respectively, resulted in a
      partial inhibition of xenogeneic NK cytotoxicity through NKG2D in (51)Cr release
      assays. In contrast, down-regulation of pMIC2 mRNA did not inhibit NK
      cytotoxicity. Human NK cytotoxicity against pEC mediated by freshly isolated or
      IL-2-activated NK cells through NKG2D was completely blocked using anti-pULBP1
      polyclonal Ab. In conclusion, this study suggests that pULBP1 is the predominant,
      if not only, functional porcine ligand for human NKG2D. Thus, the elimination of
      pULBP1 on porcine tissues represents an attractive target to protect porcine
      xenografts from human NK cytotoxicity.

PMID- 16887975
TI  - Structurally distinct ligand-binding or ligand-independent Notch1 mutants are
      leukemogenic but affect thymocyte development, apoptosis, and metastasis
      differently.
AB  - We previously found that provirus insertion in T cell tumors of mouse mammary
      tumor virus/c-myc transgenic (Tg) mice induced two forms of Notch1 mutations.
      Type I mutations generated two truncated molecules, one intracellular (IC)
      (Notch1(IC)) and one extracellular (Notch1(EC)), while in type II mutations
      Notch1 was deleted of its C terminus (Notch1(DeltaCT)). We expressed these
      mutants in Tg mice using the CD4 promoter. Both Notch1(IC) and Notch1(DeltaCT),
      but not Notch1(EC), Tg mice developed double-positive (DP) thymomas. These
      disseminated more frequently in Notch1(DeltaCT) Tg mice. Double (Notch1(IC) x
      myc) or (Notch1(DeltaCT) x myc) Tg mice developed thymoma with a much shorter
      latency than single Tg mice, providing genetic evidence of a collaboration
      between these two oncogenes. FACS analysis of preleukemic thymocytes did not
      reveal major T cell differentiation anomalies, except for a higher number of DP
      cells and an accumulation of TCR(high)CD2(high)CD25(high) DP cells in Notch1(IC),
      and less so in Notch1(DeltaCT) Tg mice. This was associated with enhanced in vivo
      thymocyte proliferation. However, Notch1(IC), but not Notch1(DeltaCT), DP
      thymocytes were protected against apoptosis induced in vivo by dexamethasone and
      anti-CD3 and in vitro by anti-CD3/CD28 Abs. This indicates that the C terminus of
      Notch1 and/or the conserved regulation by its ligands have a significant impact
      on the induced T cell phenotype. Therefore, Notch1(IC) and Notch1(DeltaCT) behave
      as oncogenes for T cells. Because these two Notch1 mutations are very similar to
      those described in some forms of human T cell leukemia, these Tg mice may
      represent relevant models of these human leukemias.

PMID- 16887976
TI  - Regulatory and effector T cell activation levels are prime determinants of in
      vivo immune regulation.
AB  - Little is known about the in vivo conditions in which CD4+CD25+ regulatory T
      cells (T(reg)) exert their suppressive effect in nonlymphopenic mice. To this
      end, we analyzed T(reg)-mediated suppression of expansion and cytokine production
      at different levels of Ag-specific CD4+CD25- T cell activation. Using Ab-mediated
      depletion of endogenous T(reg), we show that basal immunosuppression is dependent
      on effector T cell activation. These polyclonal T(reg), which were poorly
      activated in our immunization conditions, were effective in weak but not high T
      cell activation context. In contrast, the same immunization conditions led to
      proliferation of cotransferred Ag-specific T(reg). Those efficiently inhibited T
      cell proliferation and cytokine production even in strong T cell activation
      context. Interestingly, T(reg) selectively suppressed expansion or cytokine
      production depending on the experimental approach. The importance of the immune
      context for efficient suppression is further supported by the observation that
      T(reg) depletion exacerbated diabetes of NOD mice only at the early stage of the
      disease. Overall, our study suggests that T(reg)-mediated suppression depends on
      the relative activation of T(reg) and effector T cells in vivo. This balance may
      be a critical factor in the regulation of immune responses.

PMID- 16887977
TI  - Induction of allospecific tolerance by immature dendritic cells genetically
      modified to express soluble TNF receptor.
AB  - The ability of dendritic cells (DC) to initiate immune responses or induce immune
      tolerance is strictly dependent on their maturation state. TNF-alpha plays a
      pivotal role in the differentiation and maturation of DC. Blockade of TNF-alpha
      action may arrest DC in an immature state, prolonging their window of tolerogenic
      opportunity. Immature DC (imDC) were transfected with recombinant adenovirus to
      express soluble TNF-alpha receptor type I (sTNFRI), a specific inhibitor of TNF
      alpha. The capacity of sTNFRI gene-modified imDC (DC-sTNFRI) to induce immune
      tolerance was analyzed. sTNFRI expression renders imDC resistant to maturation
      induction and impairs their capacity to migrate or present Ag. This process leads
      to induction of allogeneic T cell hyporesponsiveness and the generation of IL-10
      producing T regulatory-like cells. In vivo pretreatment of transplant recipients
      with DC-sTNFRI induces long-term survival of cardiac allografts in 50% of cases,
      and leads to a substantial increase in the generation of microchimerism and T
      regulatory cell numbers. Thus, blockade of TNF-alpha action by sTNFRI genetic
      modification can inhibit the maturation of DC and potentiate the in vivo capacity
      of imDC to induce donor-specific immune tolerance and prolong allograft survival.

PMID- 16887978
TI  - Defective activation of protein kinase C and Ras-ERK pathways limits IL-2
      production and proliferation by CD4+CD25+ regulatory T cells.
AB  - Naturally occurring CD4+CD25+ regulatory T cells (Tregs), which play an important
      role in the maintenance of self-tolerance, proliferate poorly and fail to produce
      IL-2 following stimulation in vitro with peptide-pulsed or anti-CD3-treated APCs.
      When TCR proximal and distal signaling events were examined in Tregs, we observed
      impairments in the amplitude and duration of tyrosine phosphorylation when
      compared with the response of CD4+CD25- T cells. Defects were also seen in the
      activity of phospholipase C-gamma and in signals downstream of this enzyme
      including calcium mobilization, NFAT, NF-kappaB, and Ras-ERK-AP-1 activation.
      Enhanced stimulation of diacylglycerol-dependent pathways by inhibition of
      diacylglycerol metabolism could overcome the "anergic state" and support the
      ability of Tregs to up-regulate CD69, produce IL-2, and proliferate. Our results
      demonstrate that Tregs maintain their hyporesponsive state by suppressing the
      induction and propagation of TCR-initiated signals to control the accumulation of
      second messengers necessary for IL-2 production and proliferation.

PMID- 16887979
TI  - Spi-C has opposing effects to PU.1 on gene expression in progenitor B cells.
AB  - The Ets transcription factor Spi-C, expressed in B cells and macrophages, is
      closely related to PU.1 and has the ability to recognize the same DNA consensus
      sequence. However, the function of Spi-C has yet to be determined. The purpose of
      this study is to further examine Spi-C activity in B cell development. First,
      using retroviral vectors to infect PU.1(-/-) fetal liver progenitors, Spi-C was
      found to be inefficient at inducing cytokine-dependent proliferation and
      differentiation of progenitor B (pro-B) cells or macrophages relative to PU.1 or
      Spi-B. Next, Spi-C was ectopically expressed in fetal liver-derived, IL-7
      dependent pro-B cell lines. Wild-type (WT) pro-B cells ectopically expressing Spi
      C (WT-Spi-C) have several phenotypic characteristics of pre-B cells such as
      increased CD25 and decreased c-Kit surface expression. In addition, WT-Spi-C pro
      B cells express increased levels of IgH sterile transcripts and reduced levels of
      expression and transcription of the FcgammaRIIb gene. Gel-shift analysis suggests
      that Spi-C, ectopically expressed in pro-B cells, can bind PU.1 consensus sites
      in the IgH intronic enhancer and FcgammaRIIb promoter. Transient transfection
      analysis demonstrated that PU.1 functions to repress the IgH intronic enhancer
      and activate the FcgammaRIIb promoter, while Spi-C opposes these activities. WT
      Spi-C pro-B cells have reduced levels of dimethylation on lysine 9 of histone H3
      within the IgH 3' regulatory region, indicating that Spi-C can contribute to
      removal of repressive features in the IgH locus. Overall, these studies suggest
      that Spi-C may promote B cell differentiation by modulating the activity of PU.1
      dependent genes.

PMID- 16887980
TI  - Intradermal delivery of adenoviral type-35 vectors leads to high efficiency
      transduction of mature, CD8+ T cell-stimulating skin-emigrated dendritic cells.
AB  - Recombinant adenovirus (Ad) type 35 (rAd35) shows great promise as vaccine
      carrier with the advantage of low pre-existing immunity in human populations, in
      contrast to the more commonly used rAd5 vector. The rAd35 vector uses CD46 as a
      high-affinity receptor, which, unlike the rAd5 receptor, is expressed on human
      dendritic cells (DC), the most powerful APCs identified to date. In this study,
      we show that in contrast to rAd5, rAd35 infects migrated and mature CD83+
      cutaneous DC with high efficiency (up to 80%), when delivered intradermally in an
      established human skin explant model. The high transduction efficiency is in line
      with high expression levels of CD46 detected on migratory cutaneous DC, which
      proved to be further increased upon intradermal administration of GM-CSF and IL
      4. As compared with Ad5, these Ad35 infection characteristics translate into
      higher absolute numbers of skin-emigrated DC per explant that both express the
      transgene and are phenotypically mature. Finally, we demonstrate that upon
      intracutaneous delivery of a rAd35 vaccine encoding the circumsporozoite (CS)
      protein of Plasmodium falciparum, emigrated DC functionally express and process
      CS-derived epitopes and are capable of activating specific CD8+ effector T cells,
      as evidenced by activation of an HLA-A2-restricted CS-specific CD8+ T cell clone.
      Collectively, these data demonstrate the utility of rAd35 vectors for efficient
      in vivo human DC transduction.

PMID- 16887981
TI  - Constitutive activation of STAT5 supersedes the requirement for cytokine and TCR
      engagement of CD4+ T cells in steady-state homeostasis.
AB  - The transcription factor STAT5 is one of several signaling mediators activated
      via common gamma-chain cytokine receptors. As such, it plays an important role in
      lymphocyte survival and proliferation during normal homeostasis as well as under
      lymphopenic conditions. Transgenic mice expressing a constitutively activated
      form of STAT5b have been shown previously to contain increased numbers of
      peripheral CD4+CD25- T cells. To define the mechanism(s) for this occurrence, we
      have used adoptive transfer studies to examine the effects of STAT5 activity on
      steady-state CD4+ T cell homeostasis. We observed that constitutive STAT5
      signaling induced 4- to 7-fold increased levels of basal steady-state
      proliferation, which was accompanied by a comparable increase in T cell recovery.
      Most strikingly, steady-state CD4 T cell proliferation occurred independently of
      both MHC class II and IL-15. These observations demonstrate that the STAT5-driven
      pathway is important to lymphocyte homeostasis and can supersede the need for
      both TCR engagement and cytokine stimulation. This suggests that the need for TCR
      stimulation to induce common gamma-chain cytokine receptor expression, and thus
      STAT5 activation, is a key factor in maintaining normal CD4+ T cell homeostasis.

PMID- 16887982
TI  - Salmonella typhimurium infection in nonobese diabetic mice generates
      immunomodulatory dendritic cells able to prevent type 1 diabetes.
AB  - Infection, commencing across a wide age range, with a live, attenuated strain of
      Salmonella typhimurium, will halt the development of type 1 diabetes in the NOD
      mouse. The protective mechanism appears to involve the regulation of autoreactive
      T cells in a manner associated with long lasting changes in the innate immune
      compartment of these mice. We show in this study that autoreactive T cell priming
      and trafficking are altered in mice that have been infected previously by S.
      typhimurium. These changes are associated with sustained alterations in patterns
      of chemokine expression. We find that small numbers of dendritic cells from mice
      that have been previously infected with, but cleared all trace of a S.
      typhimurium infection are able to prevent the development of diabetes in the
      highly synchronized and aggressive cyclophosphamide-induced model. The effects we
      observe on autoreactive T cell trafficking are recapitulated by the
      immunomodulatory dendritic cell transfers in the cyclophosphamide model.

PMID- 16887983
TI  - Impaired intracellular calcium mobilization and NFATc1 availability in tolerant
      anti-insulin B cells.
AB  - B lymphocytes that recognize soluble self-Ags are routinely found in normal
      individuals in a functionally inactive or anergic state. Current models indicate
      that this tolerant state is maintained by interactions with self-Ags that
      uncouple the BCR from downstream signaling pathways and increase levels of free
      calcium. Contrary to this expectation, B cells that harbor anti-insulin Ig
      transgenes (125Tg) are maintained in a tolerant state even though free calcium
      levels remain normal and tyrosine kinase substrate phosphorylation is preserved
      following BCR stimulation. Under basal conditions, intracellular levels of
      inositol 1,4,5-trisphosphate are increased and NFATc1 levels are reduced in 125Tg
      B cells. The 125Tg B cells are markedly impaired in their ability to mobilize
      calcium upon stimulation with ionomycin, and BCR-induced calcium mobilization
      from internal stores is decreased. In contrast, poisoning intracellular calcium
      pumps with thapsigargin increases calcium mobilization in 125Tg B cells. Changes
      in calcium signaling are accompanied by a failure of 125Tg B cells to translocate
      NFATc1 into the nucleus following stimulation with either anti-IgM or ionomycin.
      Thus, disassociation of BCR from multiple signaling pathways is not essential for
      maintaining tolerance in anti-insulin 125Tg B cells. Rather, BCRs that are
      occupied by autologous insulin deliver signals that induce changes in
      intracellular calcium mobilization and maintain tolerance by preventing
      activation of key transcription factors such as NFAT.

PMID- 16887984
TI  - Pre-B cell receptor assesses the quality of IgH chains and tunes the pre-B cell
      repertoire by delivering differential signals.
AB  - It is well understood how a variety of Ig H and L chains, components of BCR, are
      generated in the DNA level during B cell development. However, it has remained
      largely unknown whether and how each component is monitored for its quality and
      selected before the assembly into the BCR. Here we show that muH chains produced
      by pre-B cells display a wide spectrum of ability to form the pre-BCR, which is
      composed of muH and surrogate light (SL) chains and is crucial for B cell
      development. The level of surface pre-BCR expression varies among pre-B cells,
      depending on the ability of their muH chains to pair with SL chains. The higher
      the level of pre-BCR expression by pre-B cells, the stronger their pre-BCR
      signaling, and the better they proliferate and differentiate. Thus, the extent of
      survival, proliferation, and differentiation of individual pre-B cells is
      primarily determined by the SL-pairing ability of their muH chains. Furthermore,
      IgH chains with higher potential to assemble with IgL chains appear to be
      positively selected and amplified through the assessment of their ability to pair
      with SL chains at the pre-BCR checkpoint before the assembly into the BCR. These
      results indicate that the pre-BCR assesses the quality of muH chains and tunes
      the pre-B cell repertoire by driving the preferential expansion and
      differentiation of cells with the higher quality of muH chains.

PMID- 16887985
TI  - FcR gamma presence in TCR complex of double-negative T cells is critical for
      their regulatory function.
AB  - TCRalphabeta+CD4-CD8- double-negative (DN) T regulatory (Treg) cells have
      recently been shown to suppress Ag-specific immune responses mediated by CD8+ and
      CD4+ T cells in humans and mice. Our previous study using cDNA microarray
      analysis of global gene expression showed that FcRgamma was the most highly
      overexpressed gene in functional DN Treg cell clones compared with nonfunctional
      mutant clones. In this study, we demonstrate that FcRgamma-deficient DN T cells
      display markedly reduced suppressive activity in vitro. In addition, unlike
      FcRgamma-sufficient DN T cells, FcRgamma-deficient DN T cells were unable to
      prolong donor-specific allograft survival when adoptively transferred to
      recipient mice. Protein analyses indicate that in addition to FcRgamma, DN Treg
      cell clones also express higher levels of TCRbeta, while mutant clones expressed
      higher levels of Zap70 and Lck. Within DN Treg cells, we found that FcRgamma
      associates with the TCR complex and that both FcRgamma and Syk are phosphorylated
      in response to TCR cross-linking. Inhibition of Syk signaling and FcRgamma
      expression were both found to reduce the suppressive function of DN Treg cells in
      vitro. These results indicate that FcRgamma deficiency significantly impairs the
      ability of DN Treg cells to down-regulate allogeneic immune responses both in
      vitro and in vivo, and that FcRgamma plays a role in mediating TCR signaling in
      DN Treg cells.

PMID- 16887986
TI  - Sialoadhesin promotes the inflammatory response in experimental autoimmune
      uveoretinitis.
AB  - Macrophages are a prominent component of the effector cell compartment in a
      number of CD4+ T cell-mediated organ-specific autoimmune diseases. In this study,
      we investigated the role of the sialic acid binding Ig-like lectin sialoadhesin
      (Sn, Siglec-1) in a model of interphotoreceptor retinal binding protein peptide
      induced experimental autoimmune uveoretinitis in mice with targeted deletion of
      Sn. Our data show that compared with wild-type mice, experimental autoimmune
      uveoretinitis is reduced in severity in the initial stages in the Sn knockout
      (KO) mice. In addition, there is a reduction in the proliferative capacity of T
      cells from the KO mice draining lymph nodes after immunization with
      interphotoreceptor retinal binding protein peptides, which is manifest some days
      before disease onset and persists for the duration of disease. Furthermore,
      activated T cells from the draining lymph nodes of Sn KO mice secrete lower
      levels of IFN-gamma. The data suggest a role for Sn in "fine tuning" the immune
      response to autoantigens by modulating T cell priming.

PMID- 16887987
TI  - Dendritic cell-lysosomal-associated membrane protein (LAMP) and LAMP-1-HIV-1 gag
      chimeras have distinct cellular trafficking pathways and prime T and B cell
      responses to a diverse repertoire of epitopes.
AB  - Ag processing is a critical step in defining the repertoire of epitope-specific
      immune responses. In the present study, HIV-1 p55Gag Ag was synthesized as a DNA
      plasmid with either lysosomal-associated membrane protein-1 (LAMP/gag) or human
      dendritic cell-LAMP (DC-LAMP/gag) and used to immunize mice. Analysis of the
      cellular trafficking of these two chimeras demonstrated that both molecules
      colocalized with MHC class II molecules but differed in their overall trafficking
      to endosomal/lysosomal compartments. Following DNA immunization, both chimeras
      elicited potent Gag-specific T and B cell immune responses in mice but differ
      markedly in their IL-4 and IgG1/IgG2a responses. The DC-LAMP chimera induced a
      stronger Th type 1 response. ELISPOT analysis of T cell responses to 122
      individual peptides encompassing the entire p55gag sequence (15-aa peptides
      overlapping by 11 residues) showed that DNA immunization with native gag,
      LAMP/gag, or DC-LAMP/gag induced responses to identical immunodominant CD4+ and
      CD8+ peptides. However, LAMP/gag and DC-LAMP/gag plasmids also elicited
      significant responses to 23 additional cryptic epitopes that were not recognized
      after immunization with native gag DNA. The three plasmids induced T cell
      responses to a total of 39 distinct peptide sequences, 13 of which were induced
      by all three DNA constructs. Individually, DC-LAMP/gag elicited the most diverse
      response, with a specific T cell response against 35 peptides. In addition,
      immunization with LAMP/gag and DC-LAMP/gag chimeras also promoted Ab secretion to
      an increased number of epitopes. These data indicate that LAMP-1 and DC-LAMP Ag
      chimeras follow different trafficking pathways, induce distinct modulatory immune
      responses, and are able to present cryptic epitopes.

PMID- 16887988
TI  - Preferential induction of CD4+ T cell responses through in vivo targeting of
      antigen to dendritic cell-associated C-type lectin-1.
AB  - Targeting of Ags and therapeutics to dendritic cells (DCs) has immense potential
      for immunotherapy and vaccination. Because DCs are heterogeneous, optimal
      targeting strategies will require knowledge about functional specialization among
      DC subpopulations and identification of molecules for targeting appropriate DCs.
      We characterized the expression of a fungal recognition receptor, DC-associated C
      type lectin-1 (Dectin-1), on mouse DC subpopulations and investigated the ability
      of an anti-Dectin-1 Ab to deliver Ag for the stimulation of immune responses.
      Dectin-1 was shown to be expressed on CD8alpha-CD4-CD11b+ DCs found in spleen and
      lymph nodes and dermal DCs present in skin and s.c. lymph nodes. Injection of Ag
      anti-Dectin-1 conjugates induced CD4+ and CD8+ T cell and Ab responses at low
      doses where free Ag failed to elicit a response. Notably, qualitatively different
      immune responses were generated by targeting Ag to Dectin-1 vs CD205, a molecule
      expressed on CD8alpha+CD4-CD11b- DCs, dermal DCs, and Langerhans cells. Unlike
      anti-Dectin-1, anti-CD205 conjugates failed to elicit an Ab response. Moreover,
      when conjugates were injected i.v., anti-Dectin-1 stimulated a much stronger CD4+
      T cell response and a much weaker CD8+ T cell response than anti-CD205. The
      results reveal Dectin-1 as a potential targeting molecule for immunization and
      have implications for the specialization of DC subpopulations.

PMID- 16887989
TI  - The Th2 lymphoproliferation developing in LatY136F mutant mice triggers
      polyclonal B cell activation and systemic autoimmunity.
AB  - Lat(Y136F) knock-in mice harbor a point mutation in Tyr(136) of the linker for
      activation of T cells and show accumulation of Th2 effector cells and IgG1 and
      IgE hypergammaglobulinemia. B cell activation is not a direct effect of the
      mutation on B cells since in the absence of T cells, mutant B cells do not show
      an activated phenotype. After adoptive transfer of linker for activation of T
      cell mutant T cells into wild-type, T cell-deficient recipients, recipient B
      cells become activated. We show in vivo and in vitro that the Lat(Y136F) mutation
      promotes T cell-dependent B cell activation leading to germinal center, memory,
      and plasma cell formation even in an MHC class II-independent manner. All the
      plasma and memory B cell populations found in physiological T cell-dependent B
      cell responses are found. Characterization of the abundant plasmablasts found in
      secondary lymphoid organs of Lat(Y136F) mice revealed the presence of a
      previously uncharacterized CD93-expressing subpopulation, whose presence was
      confirmed in wild-type mice after immunization. In Lat(Y136F) mice, B cell
      activation was polyclonal and not Ag-driven because the increase in serum IgG1
      and IgE concentrations involved Abs and autoantibodies with different
      specificities equally. Although the noncomplement-fixing IgG1 and IgE are the
      only isotypes significantly increased in Lat(Y136F) serum, we observed early
      onset systemic autoimmunity with nephritis showing IgE autoantibody deposits and
      severe proteinuria. These results show that Th2 cells developing in Lat(Y136F)
      mice can trigger polyclonal B cell activation and thereby lead to systemic
      autoimmune disease.

PMID- 16887990
TI  - Constitutively active beta-catenin promotes expansion of multipotent
      hematopoietic progenitors in culture.
AB  - This study was designed to investigate one component of the Wnt/beta-catenin
      signaling pathway that has been implicated in stem cell self-renewal. Retroviral
      mediated introduction of stable beta-catenin to primitive murine bone marrow
      cells allowed the expansion of multipotential c-Kit(low)Sca-1(low/-)CD19(-)
      CD11b/Mac-1(-)Flk-2(-)CD43(+)AA4.1(+)NK1.1(-)CD3(-)CD11c(-)Gr-1(-)CD45R/B220(+)
      cells in the presence of stromal cells and cytokines. They generated myeloid, T,
      and B lineage lymphoid cells in culture, but had no T lymphopoietic potential
      when transplanted. Stem cell factor and IL-6 were found to be minimal
      requirements for long-term, stromal-free propagation, and a beta-catenin
      transduced cell line was maintained for 5 mo with these defined conditions.
      Although multipotential and responsive to many normal stimuli in culture, it was
      unable to engraft several types of irradiated recipients. These findings support
      previous studies that have implicated the canonical Wnt pathway signaling in
      regulation of multipotent progenitors. In addition, we demonstrate how it may be
      experimentally manipulated to generate valuable cell lines.

PMID- 16887992
TI  - Opposite fate of endocytosed CCR7 and its ligands: recycling versus degradation.
AB  - The chemokine receptor CCR7 and its ligands CCL19 and CCL21 play a crucial role
      for the homing of lymphocytes and dendritic cells to secondary lymphoid tissues.
      Nevertheless, how CCR7 senses the gradient of chemokines and how migration is
      terminated are poorly understood. In this study, we demonstrate that CCR7(-GFP)
      is endocytosed into early endosomes containing transferrin receptor upon CCL19
      binding, but less upon CCL21 triggering. Internalization of CCR7 was independent
      of lipid rafts but relied on dynamin and Eps15 and was inhibited by hypertonic
      sucrose, suggesting clathrin-dependent endocytosis. After chemokine removal,
      internalized CCR7 recycled back to the plasma membrane and was able to mediate
      migration again. In contrast, internalized CCL19 was sorted to lysosomes for
      degradation, showing opposite fate for endocytosed CCR7 and its ligand.

PMID- 16887991
TI  - TRAIL-mediated apoptosis in HIV-1-infected macrophages is dependent on the
      inhibition of Akt-1 phosphorylation.
AB  - HIV-1 uses mononuclear phagocytes (monocytes, tissue macrophages, and dendritic
      cells) as a vehicle for its own dissemination and as a reservoir for continuous
      viral replication. The mechanism by which the host immune system clears HIV-1
      infected macrophages is not understood. TRAIL may play a role in this process.
      TRAIL is expressed on the cell membrane of peripheral immune cells and can be
      cleaved into a soluble, secreted form. The plasma level of TRAIL is increased in
      HIV-1-infected patients, particularly those with high viral loads. To study the
      effect of elevated TRAIL on mononuclear phagocytes, we used recombinant human
      (rh) TRAIL and human monocyte-derived macrophages (MDM) as an in vitro model. Our
      results demonstrated rhTRAIL-induced apoptosis in HIV-1-infected MDM and
      inhibited viral replication, while having a reduced effect on uninfected MDM. HIV
      1 infection significantly decreased Akt-1 phosphorylation; rhTRAIL exposure
      further decreased Akt-1 phosphorylation. Infection with a dominant-negative Akt-1
      adenovirus potentiated rhTRAIL-induced apoptosis, while constitutively active Akt
      1 blocked rhTRAIL-induced apoptosis in HIV-1-infected MDM. From this data we
      conclude the death ligand TRAIL preferentially provokes apoptosis of HIV-1
      infected MDM, and the mechanism is reliant upon the inhibition of Akt-1
      phosphorylation. Understanding this mechanism may facilitate the elimination of
      HIV-1-infected macrophages and lead to new therapeutic avenues for treatment of
      HIV-1 infection.

PMID- 16887993
TI  - Antigen chemically coupled to the surface of liposomes are cross-presented to
      CD8+ T cells and induce potent antitumor immunity.
AB  - We have previously demonstrated that liposomes with differential lipid components
      display differential adjuvant effects when Ags are chemically coupled to their
      surfaces. In the present study, Ag presentation of liposome-coupled OVA was
      investigated in vitro, and it was found that OVA coupled to liposomes made using
      unsaturated fatty acid was presented to both CD4+ and CD8+ T cells, whereas OVA
      coupled to liposomes made using saturated fatty acid was presented only to CD4+ T
      cells. Confocal laser scanning microscopic analysis demonstrated that a portion
      of the OVA coupled to liposomes made using unsaturated, but not saturated fatty
      acid, received processing beyond the MHC class II compartment, suggesting that
      the degradation of OVA might occur in the cytosol, and that the peptides
      generated in this manner would be presented to CD8+ T cells via MHC class I. The
      ability to induce cross-presentation of an Ag coupled to liposomes consisting of
      unsaturated fatty acid was further confirmed by in vivo induction of CTL and by
      the induction of tumor eradication in mice; E.G7 tumors in mice that received
      combined inoculation with OVA(257-264)-liposome conjugates, CpG, and anti-IL-10
      mAbs were completely eradicated. In those mice, the frequency of CD8+ T cells
      reactive with OVA(257-264) peptides in the context of H-2K(b) was significantly
      increased. These results suggested that, by choosing lipid components for
      liposomes, surface-coupled liposomal Ags might be applicable for the development
      of tumor vaccines to present tumor Ags to APCs and induce antitumor responses.

PMID- 16887994
TI  - TGF-beta-mediated suppression by CD4+CD25+ T cells is facilitated by CTLA-4
      signaling.
AB  - CD4+CD25+ T cells play a pivotal role in immunological homeostasis by their
      capacity to exert immunosuppressive activity. However, the mechanism by which
      these cells function is still a subject for debate. We previously reported that
      surface (membrane) TGF-beta produced by CD4+CD25+ T cells was an effector
      molecule mediating suppressor function. We now support this finding by imaging
      surface TGF-beta on Foxp3+CD4+CD25+ T cells in confocal fluorescence microscopy.
      Then, using a TGF-beta-sensitive mink lung epithelial cell (luciferase) reporter
      system, we show that surface TGF-beta can be activated to signal upon cell-cell
      contact. Moreover, if such TGF-beta signaling is blocked in an in vitro assay of
      CD4+CD25+ T cell suppression by a specific inhibitor of TGF-betaRI, suppressor
      function is also blocked. Finally, we address the role of CTLA-4 in CD4+CD25+ T
      cell suppression, showing first that whereas anti-CTLA-4 does not block in vitro
      suppressor function, it does complement the blocking activity of anti-TGF-beta.
      We then show with confocal fluorescence microscopy that incubation of CD4+CD25+ T
      cells with anti-CTLA-4- and rB7-1/Fc-coated beads results in accumulation of TGF
      beta at the cell-bead contact site. This suggests that CTLA-4 signaling
      facilitates TGF-beta-mediated suppression by intensifying the TGF-beta signal at
      the point of suppressor cell-target cell interaction.

PMID- 16887995
TI  - Homeostatic lymphoid chemokines synergize with adhesion ligands to trigger T and
      B lymphocyte chemokinesis.
AB  - Homeostatic chemokines such as CCL19, CCL21, and CXCL13 are known to elicit
      chemotaxis from naive T and B cells and play a critical role in lymphocyte homing
      to appropriate zones within secondary lymphoid organs (SLO). Here we tested
      whether CCL21 and CXCL13 modulate murine lymphocyte motility in the absence of
      concentration gradients, using videomicroscopy to directly observe the migration
      of single cells. CCL21 treatment of T cells induced rapid polarization and
      sustained random migration with average speeds of 5.16 +/- 2.08 microm/min; B
      cell migration (average velocity 4.10 +/- 1.58 microm/min) was similarly induced
      by CXCL13. Migration required the presence of both chemokine and adhesion ligands
      and was sustained for >24 h. Furthermore, in in vitro assays modeling the
      relative infrequency of Ag-specific T cell-dendritic cell (DC) encounters during
      primary immune responses, we found that CCL21 addition to T-DC cocultures
      accelerated the kinetics of CD69 up-regulation and enhanced by 2-fold the
      proliferation of Ag-specific T cells in a manner dependent on G-protein-coupled
      receptor signaling in T cells. These results suggest that homeostatic chemokines
      could substantially impact the dynamics and priming of lymphocytes within SLO
      even in the absence of significant concentration gradients.

PMID- 16887996
TI  - Vav1 controls DAP10-mediated natural cytotoxicity by regulating actin and
      microtubule dynamics.
AB  - The NK cell-activating receptor NKG2D recognizes several MHC class I-related
      molecules expressed on virally infected and tumor cells. Human NKG2D transduces
      activation signals exclusively via an associated DAP10 adaptor containing a YxNM
      motif, whereas murine NKG2D can signal through either DAP10 or the DAP12 adaptor,
      which contains an ITAM sequence. DAP10 signaling is thought to be mediated, at
      least in part, by PI3K and is independent of Syk/Zap-70 kinases; however, the
      exact mechanism by which DAP10 induces natural cytotoxicity is incompletely
      understood. Herein, we identify Vav1, a Rho GTPase guanine nucleotide exchange
      factor, as a critical signaling mediator downstream of DAP10 in NK cells.
      Specifically, using mice deficient in Vav1 and DAP12, we demonstrate an essential
      role for Vav1 in DAP10-induced NK cell cytoskeletal polarization involving both
      actin and microtubule networks, maturation of the cytolytic synapse, and target
      cell lysis. Mechanistically, we show that Vav1 interacts with DAP10 YxNM motifs
      through the adaptor protein Grb2 and is required for activation of PI3K-dependent
      Akt signaling. Based on these findings, we propose a novel model of ITAM
      independent signaling by Vav downstream of DAP10 in NK cells.

PMID- 16887997
TI  - ICOS-induced B7h shedding on B cells is inhibited by TLR7/8 and TLR9.
AB  - We report in this study that B7h, the ligand for the ICOS costimulatory receptor,
      is rapidly shed from mouse B cells following either ICOS binding or BCR
      engagement. Shedding occurs through proteolytic cleavage that releases the
      extracellular ICOS-binding region of B7h. Prior exposure of B7h-expressing APCs
      to ICOS-expressing cells inhibits their subsequent ability to costimulate IFN
      gamma and IL-4 production from CD4+ T cells. Shedding is regulated as TLR7/8 and
      TLR9 ligands inhibit B7h shedding. A shedding-resistant B7h mutant elicits
      greater costimulation of IFN-gamma production from CD4+ T cells than does wild
      type B7h. These data define shedding of B7h as a novel mechanism for controlling
      costimulatory signaling by B7-CD28 family members that is regulated on B cells by
      TLR signaling.

PMID- 16887999
TI  - Distinct responses of lung and spleen dendritic cells to the TLR9 agonist CpG
      oligodeoxynucleotide.
AB  - Dendritic cells (DCs) sense various components of invading pathogens via pattern
      recognition receptors such as TLRs. CpG oligodeoxynucleotides (ODNs), which mimic
      bacterial DNA, inhibit allergic airways disease and promote responses in the
      spleen to bacterial components. Because many TLR agonists are currently being
      tested for potential therapeutic effects, it is important to characterize the
      expression and function of TLRs in different tissues. We show that both myeloid
      and plasmacytoid DCs in the spleen express TLR9, the receptor for CpG ODNs, but
      lung DCs show no detectable expression in either subset. TLR4 expression in
      contrast was detected on both lung and spleen DCs. LPS was superior to CpG ODN in
      increasing the allostimulatory potential of lung DCs and their expression of
      CD40. However, both agonists efficiently stimulated spleen DCs. CpG ODNs
      administered to mice efficiently inhibited Th2 cytokine production both in the
      lung draining lymph node and in the spleen. Surprisingly, inhibition of Th2
      cytokine production was evident despite high levels of expression of GATA-3 and
      additional transcription factors that regulate Th2 responses. Although in the
      spleen CpG ODNs induced IL-6, a key cytokine induced via TLR9-MyD88 signaling, no
      IL-6 was detectable in lung LN cells. These studies show for the first time that
      lung DCs lack TLR9 expression, but, despite this deficiency, CpG ODNs induce
      potent inhibitory effects on Th2 cytokine production in the lung without inducing
      expression of the proinflammatory cytokine, IL-6, which has been linked to
      chronic diseases in the lung and the gut.

PMID- 16887998
TI  - B7RP-1-ICOS interactions are required for optimal infection-induced expansion of
      CD4+ Th1 and Th2 responses.
AB  - Although initial reports linked the costimulatory molecule ICOS preferentially
      with the development of Th2 cells, there is evidence that it is not required for
      protective type 2 immunity to helminths and that it contributes to Th1 and Th2
      responses to other parasites. To address the role of ICOS in the development of
      infection-induced polarized Th cells, ICOS(-/-) mice were infected with Trichuris
      muris or Toxoplasma gondii. Wild-type mice challenged with T. muris developed Th2
      responses and expelled these helminths by day 18 postinfection, whereas ICOS(-/-)
      mice failed to clear worms and produced reduced levels of type 2 cytokines.
      However, by day 35 postinfection, ICOS(-/-) mice were able to mount an effective
      Th2 response and worms were expelled. This delay in protective immunity was
      associated with a defect in infection-induced increases in the number of
      activated and proliferating CD4+ T cells. Similarly, following challenge with T.
      gondii ICOS was required for optimal proliferation by CD4+ T cells. However, the
      reduced number of activated CD4+ T cells and associated defect in the production
      of IFN-gamma did not result in increased susceptibility to T. gondii, but rather
      resulted in decreased CNS pathology during the chronic phase of this infection.
      Taken together, these data are consistent with a model in which ICOS is not
      involved in dictating polarity of the Th response but rather regulates the
      expansion of these subsets.

PMID- 16888000
TI  - Activation of NFAT signal in vivo leads to osteopenia associated with increased
      osteoclastogenesis and bone-resorbing activity.
AB  - The transcription factor family member NFAT plays an important role in the
      regulation of osteoclast differentiation. However, the role of NFAT in
      osteoclasts in vivo is still not fully understood. Thus, we generated transgenic
      mice in which constitutively active-NFAT1/NFATc2 (CA-NFAT1) is specifically
      expressed in the osteoclast lineage, using the tartrate-resistant acid
      phosphatase gene promoter. Both x-ray and histological analyses demonstrated an
      osteopenic bone phenotype in the CA-NFAT1 transgenic mice, whereas the number of
      tartrate-resistant acid phosphatase-positive osteoclasts was markedly higher in
      the long bones of these mice. Furthermore, the bone-resorbing activity of mature
      osteoclasts derived from the transgenic mice was much higher than that of wild
      type mice. Interestingly, the introduction of CA-NFAT1 into osteoclasts or RAW264
      cells increased the expression and activity of c-Src and stimulated actin ring
      formation. In contrast, CA-NFAT1 or GFP-tagged VIVIT peptide, a specific
      inhibitor of NFAT, did not affect the survival of mature osteoclasts.
      Collectively, our data indicate that NFAT controls bone resorption in vivo by
      stimulating the differentiation and functioning of osteoclasts but not their
      survival.

PMID- 16888001
TI  - Cyclooxygenase-2 inhibitor enhances the efficacy of a breast cancer vaccine: role
      of IDO.
AB  - We report that administration of celecoxib, a specific cyclooxygenase-2 (COX-2)
      inhibitor, in combination with a dendritic cell-based cancer vaccine
      significantly augments vaccine efficacy in reducing primary tumor burden,
      preventing metastasis, and increasing survival. This combination treatment was
      tested in MMTV-PyV MT mice that develop spontaneous mammary gland tumors with
      metastasis to the lungs and bone marrow. Improved vaccine potency was associated
      with an increase in tumor-specific CTLs. Enhanced CTL activity was attributed to
      a significant decrease in levels of tumor-associated IDO, a negative regulator of
      T cell activity. We present data suggesting that inhibiting COX-2 activity in
      vivo regulates IDO expression within the tumor microenvironment; this is further
      corroborated in the MDA-MB-231 human breast cancer cell line. Thus, a novel
      mechanism of COX-2-induced immunosuppression via regulation of IDO has emerged
      that may have implications in designing future cancer vaccines.

PMID- 16888002
TI  - A pathogenic role for CD8+ T cells in a spontaneous model of demyelinating
      disease.
AB  - Transgenic (Tg) mice that overexpress the costimulatory ligand B7.2/CD86 on
      microglia spontaneously develop a T cell-mediated demyelinating disease.
      Characterization of the inflammatory infiltrates in the nervous tissue revealed a
      predominance of CD8+ T cells, suggesting a prominent role of this T cell subset
      in the pathology. In this study, we show that the same neurological disease
      occurred in Tg mice deficient in the generation of CD4+ T cells, with an earlier
      time of onset. Analysis of the CD8+ T cell repertoire at early stage of disease
      revealed the presence of selected clonal expansions in the CNS but not in
      peripheral lymphoid organs. We further show that Tg animals deficient in IFN
      gamma receptor expression were completely resistant to disease development.
      Microglia activation that is an early event in disease development is IFN-gamma
      dependent and thus appears as a key element in disease pathogenesis.
      Collectively, our data indicate that the spontaneous demyelinating disease in
      this animal model occurs as a consequence of an inflammatory response initiated
      through the activation of CNS-specific CD8+ T cells by Tg expression of B7.2
      within the target organ. Thus, autoreactive CD8+ T cells can contribute directly
      to the pathogenesis of neuroinflammatory diseases such as multiple sclerosis.

PMID- 16888003
TI  - B cells expressing a natural polyreactive autoantibody have a distinct phenotype
      and are overrepresented in immunoglobulin heavy chain transgenic mice.
AB  - Despite stringent regulation of disease-associated autoantibodies, a substantial
      proportion of circulating Abs in sera of healthy individuals exhibit self
      reactivity. These Abs are referred to as naturally occurring or natural
      autoantibodies (NAAs). To understand the origin and function of NAAs, we have
      generated a new site-directed transgenic mouse model in which a prerearranged VDJ
      gene coding for the H chain of a typical polyreactive NAA, ppc1-5, is inserted
      into the IgH locus. This H chain, when combined with its original L chain, the
      lambda1 L chain, yields a NAA that characteristically binds a variety of self and
      non-self Ags including ssDNA, actin, ubiquitin, and nitrophenyl phosphocholine.
      Despite their autoreactivity, B cells expressing ppc1-5H/lambda1 NAA are not
      negatively selected, but rather are overrepresented in the transgenic mice. The
      shift toward lambda1 expression mainly occurs during the transition of immature
      to mature B cells in the spleen, suggesting a BCR selection process. The ppc1
      5H/lambda1 B cells exhibit a phenotype that is different from those of the known
      mature B cell populations, and they are located predominantly in the lymphoid
      follicles of the spleen and the lymph nodes. These B cells are functionally
      active, producing high levels of Abs in vivo and responding well to BCR
      stimulation in vitro. The findings indicate that the ppc1-5/lambda1 natural
      autoantibodies originate from a distinct B cell subset that may be positively
      selected by virtue of its poly/autoreactivity.

PMID- 16888004
TI  - Structure-activity profiles of Ab-derived TNF fusion proteins.
AB  - TNF application in humans is limited by severe side effects, including life
      threatening symptoms of shock. Therefore, TNF can be successfully applied as a
      tumor therapeutic reagent only under conditions that prevent its systemic action.
      To overcome this limitation, genetic fusion of TNF to tumor-selective Abs is a
      favored strategy to increase site-specific cytokine targeting. Because wild-type
      TNF displays its bioactivity as noncovalently linked homotrimer, the challenge is
      to define structural requirements for a TNF-based immunokine format with
      optimized structure-activity profile. We compared toxicity and efficacy of a
      dimerized CH2/CH3 truncated IgG1-TNF fusion protein and a single-chain variable
      fragment-coupled TNF monomer recognizing fibroblast-activating protein. The
      former construct preserves its dimeric structure stabilized by the natural
      disulfide bond IgG1 hinge region, while the latter trimerizes under native
      conditions. Analysis of complex formation of wild-type TNF and of both fusion
      proteins with TNFR type 1 (TNF-R1) using surface plasmon resonance correlated
      well with in vitro and in vivo toxicity data. There is strong evidence that TNF
      subunits in a trimeric state display similar toxicity profiles despite genetic
      fusion to single-chain variable fragment domains. However, LD(50) of either
      immunodeficient BALB/c nu/nu or immunocompetent BALB/c mice was significantly
      decreased following administration of TNF in the formation of IgG1-derived
      dimeric fusion protein. Reduction of unspecific peripheral complexation of TNF-R1
      resulted in higher anticancer potency by immunotargeting of fibroblast-activating
      protein-expressing xenografts. The broader therapeutic window of the IgG1-derived
      TNF fusion protein favors the dimeric TNF-immunokine format for systemic TNF
      based tumor immunotherapy.

PMID- 16888005
TI  - Activation of murine CD4+ and CD8+ T lymphocytes leads to dramatic remodeling of
      N-linked glycans.
AB  - Differentiation and activation of lymphocytes are documented to result in changes
      in glycosylation associated with biologically important consequences. In this
      report, we have systematically examined global changes in N-linked glycosylation
      following activation of murine CD4 T cells, CD8 T cells, and B cells by MALDI-TOF
      mass spectrometry profiling, and investigated the molecular basis for those
      changes by assessing alterations in the expression of glycan transferase genes.
      Surprisingly, the major change observed in activated CD4 and CD8 T cells was a
      dramatic reduction of sialylated biantennary N-glycans carrying the terminal
      NeuGcalpha2-6Gal sequence, and a corresponding increase in glycans carrying the
      Galalpha1-3Gal sequence. This change was accounted for by a decrease in the
      expression of the sialyltransferase ST6Gal I, and an increase in the expression
      of the galactosyltransferase, alpha1-3GalT. Conversely, in B cells no change in
      terminal sialylation of N-linked glycans was evident, and the expression of the
      same two glycosyltransferases was increased and decreased, respectively. The
      results have implications for differential recognition of activated and
      unactivated T cells by dendritic cells and B cells expressing glycan-binding
      proteins that recognize terminal sequences of N-linked glycans.

PMID- 16888006
TI  - Identification of PP1alpha as a caspase-9 regulator in IL-2 deprivation-induced
      apoptosis.
AB  - One of the mechanisms that regulate cell death is the reversible phosphorylation
      of proteins. ERK/MAPK phosphorylates caspase-9 at Thr(125), and this
      phosphorylation is crucial for caspase-9 inhibition. Until now, the phosphatase
      responsible for Thr(125) dephosphorylation has not been described. Here, we
      demonstrate that in IL-2-proliferating cells, phosphorylated serine/threonine
      phosphatase type 1alpha (PP1alpha) associates with phosphorylated caspase-9. IL-2
      deprivation induces PP1alpha dephosphorylation, which leads to its activation
      and, as a consequence, dephosphorylation and activation of caspase-9 and
      subsequent dissociation of both molecules. In cell-free systems supplemented with
      ATP caspase-9 activation is induced by addition of cytochrome c and we show that
      in this process PP1alpha is indispensable for triggering caspase-9 as well as
      caspase-3 cleavage and activation. Moreover, PP1alpha associates with caspase-9
      in vitro and in vivo, suggesting that it is the phosphatase responsible for
      caspase-9 dephosphorylation and activation. Finally, we describe two novel
      phosphatase-binding sites different from the previously described PP1alpha
      consensus motifs, and we demonstrate that these novel sites mediate the
      interaction of PP1alpha with caspase-9.

PMID- 16888008
TI  - Conserved functions of Ikaros in vertebrate lymphocyte development: genetic
      evidence for distinct larval and adult phases of T cell development and two
      lineages of B cells in zebrafish.
AB  - Zebrafish has been advocated as an alternative animal model to study lymphocyte
      development, although the similarities in the genetic requirements of
      lymphopoiesis between fish and mammals have not yet been investigated. In this
      study, we examine the role of the transcription factor Ikaros in zebrafish
      lymphopoiesis. In fish larvae homozygous for an ikaros allele predicted to lack
      the C-terminal zinc fingers, T lymphopoiesis is absent; the presence of
      V(H)DmuJmu rearrangements in adolescent fish is delayed in mutants. In adolescent
      mutant fish, T cells expressing tcrb and tcrd and B cells expressing igm are
      formed with low efficiency and display an oligoclonal Ag receptor repertoire. By
      contrast, B cells expressing the igz isotype do not develop, providing genetic
      evidence for two separate B cell lineages in zebrafish. Thus, Ikaros appears to
      play similar roles in fish and mammalian lymphopoiesis.

PMID- 16888007
TI  - Diverse immunoglobulin light chain organizations in fish retain potential to
      revise B cell receptor specificities.
AB  - We have characterized the genomic organization of the three zebrafish L chain
      isotypes and found they all differed from those reported in other teleost fishes.
      Two of the zebrafish L chain isotypes are encoded by two loci, each carrying
      multiple V gene segments. To understand the derivation of these L chain genes and
      their organizations, we performed phylogenetic analyses and show that IgL
      organization can diverge considerably among closely related species. Except in
      zebrafish, the teleost fish IgL each contain only two to four recombinogenic
      components (one to three V, one J) and exist in multiple copies. BCR
      heterogeneity can be generated, but this arrangement apparently provides neither
      combinatorial diversification nor an opportunity for the secondary rearrangements
      that, in mammals, take place during receptor editing, a process crucial to the
      promotion of tolerance in developing lymphocytes. Examination of the zebrafish
      IgL recombination possibilities gave insight into how the suppression of self
      reactivity by receptor editing might be managed, including in miniloci. We
      suggest that, despite the diverse IgL organizations in early and higher
      vertebrates, two elements essential to generating the Ab repertoire are retained:
      the numerous genes/loci for ligand-binding diversification and the potential for
      correcting unwanted specificities that arise.

PMID- 16888009
TI  - TCR-alpha CDR3 loop audition regulates positive selection.
AB  - How positive selection molds the T cell repertoire has been difficult to examine.
      In this study, we use TCR-beta-transgenic mice in which MHC shapes TCR-alpha use.
      Differential AV segment use is directly related to the constraints placed on the
      composition of the CDR3 loops. Where these constraints are low, efficient
      selection of alphabeta pairs follows. This mode of selection preferentially uses
      favored AV-AJ rearrangements and promotes diversity. Increased constraint on the
      alpha CDR3 loops leads to inefficient selection associated with uncommon
      recombination events and limited diversity. Further, the two modes of selection
      favor alternate sets of AJ segments. We discuss the relevance of these findings
      to the imprint of self-MHC restriction and peripheral T cell activation.

PMID- 16888010
TI  - Autoantibodies from synovial lesions in chronic, antibiotic treatment-resistant
      Lyme arthritis bind cytokeratin-10.
AB  - Although the causative agent of Lyme disease is definitively known to be the tick
      borne spirochete, Borrelia burgdorferi, the etiology of chronic joint
      inflammation that ensues in a subset of patients remains less well understood.
      Persistence of arthritis after apparent eradication of the spirochete suggests an
      autoimmune reaction downstream of the original bacterial infection. We have
      generated recombinant Ab probes from synovial lesions within affected arthritic
      joints in an attempt to recapitulate disease-relevant Ag-binding specificities at
      the site of injury. Using this panel of intra-articular probes, as well as Ab
      fragments derived from patient peripheral blood, we have identified cytokeratin
      10, present in synovial microvascular endothelium, as a target ligand and a
      putative autoantigen in chronic, antibiotic treatment-resistant Lyme arthritis.
      Furthermore, there is cross-reactivity between cytokeratin 10 and a prominent B.
      burgdorferi Ag, outer surface protein A. Release of the self protein in the
      context of inflammation-induced tissue injury and the resulting in situ response
      to it could set in motion a feed-forward loop, which amplifies the inflammatory
      process, thereby rendering it chronic and self-perpetuating, even in the absence
      of the inciting pathogen.

PMID- 16888011
TI  - E2A promotes the survival of precursor and mature B lymphocytes.
AB  - The basic helix-loop-helix transcription factor E2A is an essential regulator of
      B lymphocyte lineage commitment and is required to activate the expression of
      numerous B lineage-specific genes. Studies involving ectopic expression of Id
      proteins, which inhibit E2A as well as other basic helix-loop-helix proteins such
      as HEB, suggest additional roles of E2A at later stages of B cell development. We
      use E2A-deficient and E2A and HEB double-deficient pre-B cell lines to directly
      assess the function of E2A and HEB in B cell development after lineage
      commitment. We show that, in contrast to the established role of E2A in lineage
      commitment, elimination of E2A and HEB in pre-B cell lines has only a modest
      negative impact on B lineage gene expression. However, E2A single and E2A and HEB
      double-deficient but not HEB single-deficient cell lines show dramatically
      enhanced apoptosis upon growth arrest. To address the possible role of E2A in the
      regulation of B cell survival in vivo, we crossed IFN-inducible Cre-transgenic
      mice to E2A conditional mice. Cre-mediated E2A deletion resulted in a block in
      bone marrow B cell development and a significant reduction in the proportion and
      total number of splenic B cells in these mice. We show that Cre-mediated deletion
      of E2A in adoptively transferred mature B cells results in the rapid depletion of
      the transferred population within 24 h of Cre induction. These results reveal
      that E2A is not required to maintain B cell fate but is essential in promoting
      pre-B and B cell survival.

PMID- 16888012
TI  - Identification and characterization of a FcR homolog in an ectothermic
      vertebrate, the channel catfish (Ictalurus punctatus).
AB  - An FcR homolog (IpFcRI), representing the first such receptor from an ectothermic
      vertebrate, has been identified in the channel catfish (Ictalurus punctatus).
      Mining of the catfish expressed sequence tag databases using mammalian FcR
      sequences for CD16, CD32, and CD64 resulted in the identification of a teleost Ig
      binding receptor. IpFcRI is encoded by a single-copy gene containing three Ig C2
      like domains, but lacking a transmembrane segment and cytoplasmic tail. The
      encoded Ig domains of IpFcRI are phylogenetically and structurally related to
      mammalian FcR and the presence of a putative Fc-binding region appears to be
      conserved. IpFcRI-related genomic sequences are also present in both pufferfish
      and rainbow trout, indicating the likely presence of a soluble FcR in other fish
      species. Northern blot and qualitative PCR analyses demonstrated that IpFcRI is
      primarily expressed in IgM-negative leukocytes derived from the lymphoid kidney
      tissues and PBL. Significantly lower levels of IpFcRI expression were detected in
      catfish clonal leukocyte cell lines. Using the native leader, IpFcRI was secreted
      when transfected into insect cells and importantly the native IpFcRI glycoprotein
      was detected in catfish plasma using a polyclonal Ab. Recombinant IpFcRI binds
      catfish IgM as assessed by both coimmunoprecipation and cell transfection studies
      and it is presumed that it functions as a secreted FcR akin to the soluble FcR
      found in mammals. The identification of an FcR homolog in an ectothermic
      vertebrate is an important first step toward understanding the evolutionary
      history and functional importance of vertebrate Ig-binding receptors.

PMID- 16888013
TI  - CD8+ T lymphocyte-mediated loss of marginal metallophilic macrophages following
      infection with Plasmodium chabaudi chabaudi AS.
AB  - The splenic architecture is essential for the quick resolution of a primary
      infection with Plasmodium. A critical component of this architecture is the
      marginal zone (MZ), an area of the spleen that separates the reticuloendothelial
      red pulp of the spleen from the lymphoid white pulp compartment. There are two
      unique macrophage populations found in the MZ: MZ macrophages (MZM) found on the
      outer border of the MZ, and marginal metallophilic macrophages (MMM) found on the
      inner border, adjacent to the white pulp. We investigated the homeostasis of MMM
      and MZM following infection with Plasmodium chabaudi and demonstrated that a
      complete loss of both MMM and MZM occurred by the time of peak parasitemia, 8
      days after infection. The loss was not induced by up-regulation of the
      inflammatory cytokines TNF or IFN-gamma. In contrast, following only CD8+ T cell
      depletion (not dendritic cell), MMM but not MZM were retained, implicating CD8+ T
      cells in the P. chabaudi-induced loss of MMM. Retention of MMM occurred in mice
      deficient in CD95, CD95-ligand, and perforin, indicating that these signals are
      involved in the death pathway of MMM. These data have significant implications
      for the understanding of the immune-mediated pathology of the spleen as a result
      of infection with Plasmodium.

PMID- 16888014
TI  - Nuclear accumulation of cRel following C-terminal phosphorylation by TBK1/IKK
      epsilon.
AB  - The NF-kappaB transcription factors are key regulators of immunomodulatory, cell
      cycle, and developmental gene regulation. NF-kappaB activity is mainly regulated
      through the phosphorylation of IkappaB by the IkappaB kinase (IKK) complex
      IKKalphabetagamma, leading to proteasome-mediated degradation of IkappaB, nuclear
      translocation of NF-kappaB dimers, DNA binding, and gene induction. Additionally,
      direct posttranslational modifications of NF-kappaB p65 and cRel subunits
      involving C-terminal phosphorylation has been demonstrated. The noncanonical IKK
      related homologs, TNFR-associated factor family member-associated NF-kappaB
      activator (TANK)-binding kinase (TBK)1 and IKKepsilon, are also thought to play a
      role in NF-kappaB regulation, but their functions remain unclear. TBK1 and
      IKKepsilon were recently described as essential regulators of IFN gene activation
      through direct phosphorylation of the IFN regulatory factor-3 and -7
      transcription factors. In the present study, we sought to determine whether
      IKKepsilon and TBK1 could modulate cRel activity via phosphorylation. TBK1 and
      IKKepsilon directly phosphorylate the C-terminal domain of cRel in vitro and in
      vivo and regulate nuclear accumulation of cRel, independently of the classical
      IkappaB/IKK pathway. IkappaBalpha degradation is not affected, but rather
      IKKepsilon-mediated phosphorylation of cRel leads to dissociation of the
      IkappaBalpha-cRel complex. These results illustrate a previously unrecognized
      aspect of cRel regulation, controlled by direct IKKepsilon/TBK1 phosphorylation.

PMID- 16888015
TI  - Local CD11c+ MHC class II- precursors generate lung dendritic cells during
      respiratory viral infection, but are depleted in the process.
AB  - Increases in numbers of lung dendritic cells (DC) observed during respiratory
      viral infections are assumed to be due to recruitment from bone marrow
      precursors. No local production has been demonstrated. In this study, we isolated
      defined populations of murine lung cells based on CD11c and MHC class II (MHC II)
      expression. After culture for 12 days with GM-CSF, we analyzed cell numbers, DC
      surface markers, and Ag-presenting capacity. Only CD11c+ MHC II- cells from naive
      mice proliferated, yielding myeloid DC, which induced Ag-specific proliferation
      of naive T cells. After respiratory syncytial virus (RSV) infection, numbers of
      pulmonary CD11c+ MHC II- precursor cells were significantly reduced and DC could
      not be generated. Moreover, RSV infection prevented subsequent in vivo expansion
      of pulmonary DC in response to influenza infection or LPS treatment. These
      results provide direct evidence of local generation of fully functional myeloid
      DC in the lung from CD11c+ MHC II(-) precursor cells that are depleted by RSV
      infection, leading to an inability to expand lung DC numbers in response to
      subsequent viral infection or exposure to bacterial products. This depletion of
      local DC precursors in respiratory viral infections may be important in
      explaining complex interactions between multiple and intercurrent pulmonary
      infections.

PMID- 16888016
TI  - CD46 (membrane cofactor protein) acts as a human epithelial cell receptor for
      internalization of opsonized uropathogenic Escherichia coli.
AB  - Escherichia coli is a common urinary pathogen whose uptake into epithelial cells
      is mediated by attachment through type 1 fimbriae. In this study, we show by
      using using human urinary tract epithelial cells that maximal internalization of
      E. coli is achieved only when bacteria are opsonized with complement. The
      concentrations of complement proteins in the urine rise sufficiently during
      infection to allow bacterial opsonization. The complement regulatory protein,
      CD46 (membrane cofactor protein), acts in cohort with fimbrial adhesion to
      promote the uptake of pathogenic E. coli. This uptake is inhibited by RNA
      interference to lower the expression of CD46 and by soluble CD46 that will
      competitively inhibit opsonized bacteria binding to cell surface CD46. We propose
      that efficient internalization of uropathogenic E. coli by the human urinary
      tract depends on cooperation between fimbrial-mediated adhesion and C3 receptor
      (CD46)-ligand interaction. Complement receptor-ligand interaction could pose a
      new target for interrupting the cycle of reinfection due to intracellular
      bacteria.

PMID- 16888018
TI  - IL-10 is required for optimal CD8 T cell memory following Listeria monocytogenes
      infection.
AB  - IL-10 is an important immunoregulatory cytokine that plays a central role in
      maintaining a balance between protective immunity against infection and limiting
      proinflammatory responses to self or cross-reactive Ags. We examined the full
      effects of IL-10 deficiency on the establishment and quality of T cell memory
      using murine listeriosis as a model system. IL-10(-/-) mice had reduced bacterial
      loads and a shorter duration of primary infection than did wild-type mice.
      However, the number of Ag-specific T cells in secondary lymphoid and nonlymphoid
      organs was diminished in IL-10(-/-) mice, compared with wild-type mice, at the
      peak of the effector response. Moreover, the frequency and protective capacity of
      memory T cells also were reduced in IL-10(-/-) mice when assessed up to 100 days
      postinfection. Remarkably, this effect was more pronounced for CD8 T cells than
      CD4 T cells. To address whether differences in the number of bacteria and
      duration of primary infection could explain these findings, both strains of mice
      were treated with ampicillin 24 hours after primary infection. Despite there
      being more comparable bacterial loads during primary infection, IL-10(-/-) mice
      still generated fewer memory CD8 T cells and were less protected against
      secondary infection than were wild-type mice. Finally, the adoptive transfer of
      purified CD8 T cells from previously infected wild-type mice into naive
      recipients conferred better protection than the transfer of CD8 T cells from
      immune IL-10(-/-) mice. Overall, these data show that IL-10 plays an unexpected
      role in promoting and/or sustaining CD8 T cell memory following Listeria
      monocytogenes infection.

PMID- 16888017
TI  - Subunit recombinant vaccine protects against monkeypox.
AB  - The smallpox vaccine Dryvax, a live vaccinia virus (VACV), protects against
      smallpox and monkeypox, but is contraindicated in immunocompromised individuals.
      Because Abs to VACV mediate protection, a live virus vaccine could be substituted
      by a safe subunit protein-based vaccine able to induce a protective Ab response.
      We immunized rhesus macaques with plasmid DNA encoding the monkeypox orthologs of
      the VACV L1R, A27L, A33R, and B5R proteins by the intradermal and i.m. routes,
      either alone or in combination with the equivalent recombinant proteins produced
      in Escherichia coli. Animals that received only DNA failed to produce high titer
      Abs, developed innumerable skin lesions after challenge, and died in a manner
      similar to placebo controls. By contrast, the animals vaccinated with proteins
      developed moderate to severe disease (20-155 skin lesions) but survived.
      Importantly, those immunized with DNA and boosted with proteins had mild disease
      with 15 or fewer lesions that resolved within days. DNA/protein immunization
      elicited Th responses and binding Ab titers to all four proteins that correlated
      negatively with the total lesion number. The sera of the immunized macaques
      recognized a limited number of linear B cell epitopes that are highly conserved
      among orthopoxviruses. Their identification may guide future efforts to develop
      simpler, safer, and more effective vaccines for monkeypox and smallpox.

PMID- 16888020
TI  - Toxoplasma gondii genotype determines MyD88-dependent signaling in infected
      macrophages.
AB  - Infection of mouse macrophages with Toxoplasma gondii elicits MAPK activation and
      IL-12 production, but host cell signaling pathways have not been clearly
      delineated. Here, we compared macrophage signaling in response to high virulence
      type I (RH) vs low virulence type II (ME49) strain infection. Tachyzoites of both
      strains induced p38 MAPK-dependent macrophage IL-12 release, although ME49
      elicited 2- to 3-fold more cytokine than RH. IL-12 production was largely
      restricted to infected cells in each case. RH-induced IL-12 release did not
      require MyD88, whereas ME49-triggered IL-12 production was substantially
      dependent on this TLR/IL-1R adaptor molecule. MyD88 was also not required for RH
      stimulated p38 MAPK activation, which occurred in the absence of detectable
      upstream p38 MAPK kinase activity. In contrast, ME49-driven p38 MAPK activation
      displayed an MyD88-dependent component. This parasite strain also induced MyD88
      dependent activation of MKK4, an upstream activator of p38 MAPK. The results
      suggest that RH triggers MAPK activation and IL-12 production using MyD88
      independent signaling, whereas ME49 uses these pathways as well as MyD88
      dependent signaling cascades. Differences in host signaling pathways triggered by
      RH vs ME49 may contribute to the high and low virulence characteristics displayed
      by these parasite strains.

PMID- 16888019
TI  - NK cells use NKG2D to recognize a mouse renal cancer (Renca), yet require
      intercellular adhesion molecule-1 expression on the tumor cells for optimal
      perforin-dependent effector function.
AB  - The NKG2D receptor on NK cells can recognize a variety of ligands on the tumor
      cell surface. Using a mouse renal cancer (Renca), we show that NKG2D recognition
      by NK cells was crucial for their ability to limit tumor metastases in vivo in
      both liver and lungs using perforin-dependent effector mechanisms. However, for
      the R331 cell line established from Renca, NKG2D recognition and perforin
      dependent lysis played no role in controlling liver metastases. R331 cells were
      also more resistant to perforin-dependent lysis by NK cells in vitro. We
      therefore used these phenotypic differences between Renca and R331 to further
      investigate the crucial receptor:ligand interactions required for triggering
      lytic effector functions of NK cells. Reconstitution of R331 cells with ICAM-1,
      but not Rae-1gamma, restored NKG2D-mediated, perforin-dependent lysis.
      Interestingly, R331 cells were efficiently lysed by NK cells using death ligand
      mediated apoptosis. This death ligand-mediated killing did not depend on NKG2D
      recognition of its ligands on tumor cells. This result suggests that the
      intracellular signaling in NK cells required for perforin and death ligand
      mediated lysis of tumor target cell are quite distinct, and activation of both of
      these antitumor lytic effector functions of NK cells could improve therapeutic
      benefits for certain tumors.

PMID- 16888021
TI  - Heme oxygenase-1 mediates the anti-inflammatory effects of acute alcohol on IL-10
      induction involving p38 MAPK activation in monocytes.
AB  - Inflammation and immunoregulatory cytokines play a central role in alcohol
      induced liver damage. We previously reported that acute alcohol treatment
      augments IL-10 and inhibits TNF-alpha production in monocytes. Heme oxygenase-1
      (HO-1), a stress-inducible protein, also regulates IL-10 and TNF-alpha
      production. Here, we report that augmentation of LPS-induced IL-10 production by
      alcohol was prevented by inhibition of HO-1 activity. Acute ethanol increased LPS
      induced enzyme activity and RNA levels of HO-1, and DNA binding of AP-1, a
      transcription factor essential in HO-1 regulation. LPS-induced phospho-p38 MAPK
      levels were augmented by ethanol treatment and the p38 inhibitor, SB203580,
      prevented both the ethanol-induced increase in IL-10 production and the
      inhibitory effect of ethanol on TNF-alpha production. Ethanol-induced down
      regulation of TNF-alpha production was abrogated by inhibition of HO-1. We found
      that LPS-induced activation of NF-kappaB, a regulator of TNF-alpha, was inhibited
      by both ethanol treatment and HO-1 activation, but the ethanol-induced inhibition
      of NF-kappaB was HO-1 independent. In LPS-challenged mice in vivo, both acute
      alcohol administration and HO-1 activation augmented IL-10 and inhibited TNF
      alpha serum levels. These results show that 1) acute alcohol augments HO-1
      activation in monocytes, 2) HO-1 activation plays a role in alcohol-induced
      augmentation of IL-10 production likely via increased p38 MAPK activation, and 3)
      HO-1 activation is involved in attenuation of TNF-alpha production by alcohol
      independent of inhibition of NF-kappaB activation by alcohol. Thus, HO-1
      activation is a key mediator of the anti-inflammatory effects of acute alcohol on
      monocytes.

PMID- 16888022
TI  - Inflammation-responsive transcription factor SAF-1 activity is linked to the
      development of amyloid A amyloidosis.
AB  - Abundantly expressed serum amyloid A (SAA) protein under chronic inflammatory
      conditions gives rise to insoluble aggregates of SAA derivatives in multiple
      organs resulting in reactive amyloid A (AA) amyloidosis, a consequence of
      rheumatoid arthritis, Crohn's disease, ankylosing spondylitis, familial
      Mediterranean fever, and Castleman's disease. An inflammation-responsive
      transcription factor, SAF (for SAA activating factor), has been implicated in the
      sustained expression of amyloidogenic SAA under chronic inflammatory conditions.
      However, its role in the pathogenesis of AA amyloidosis has thus far remained
      obscure. In this paper we have shown that SAF-1, a major member of the SAF
      family, is abundantly present in human AA amyloidosis patients. To assess whether
      SAF-1 is directly linked to the pathogenesis of AA amyloidosis, we have developed
      a SAF-1 transgenic mouse model. SAF-1-overexpressing mice spontaneously developed
      AA amyloidosis at the age of 14 mo or older. Immunohistochemical analysis
      confirmed the nature of the amyloid deposits as an AA type derived from
      amyloidogenic SAA1. Furthermore, SAF-1 transgenic mice rapidly developed severe
      AA amyloidosis in response to azocasein injection, indicating increased
      susceptibility to inflammation. Also, during inflammation SAF-1 transgenic mice
      exhibited a prolonged acute phase response, leading to an extended period of SAA
      synthesis. Together, these results provide direct evidence that SAF-1 plays a key
      role in the development of AA amyloidosis, a consequence of chronic inflammation.

PMID- 16888023
TI  - TWEAK is a novel arthritogenic mediator.
AB  - TNF-like weak inducer of apoptosis (TWEAK) is a TNF family member with
      pleiotropic effects on a variety of cell types, one of which is the induction of
      proinflammatory cytokines by synovial fibroblasts derived from rheumatoid
      arthritis (RA) patients. In this study, we report that the serum TWEAK level was
      dramatically elevated during mouse collagen-induced arthritis (CIA) and blocking
      TWEAK by a neutralizing mAb significantly reduced the clinical severity of CIA.
      Histological analyses also revealed that TWEAK inhibition diminished joint
      inflammation, synovial angiogenesis, as well as cartilage and bone erosion. Anti
      TWEAK treatment proved efficacious when administered just before the disease
      onset but not during the priming phase of CIA. Consistent with this, TWEAK
      inhibition did not affect either cellular or humoral responses to collagen. In
      contrast, TWEAK inhibition significantly reduced serum levels of a panel of
      arthritogenic mediators, including chemokines such as MIP-1beta (CCL-4),
      lymphotactin (XCL-1), IFN-gamma-inducible protein 10 (IP-10) (CXCL-10), MCP-1
      (CCL-2), and RANTES (CCL-5), as well as the matrix metalloprotease-9. Exploring
      the possible role of the TWEAK/Fn14 pathway in human RA pathogenesis, we showed
      that TWEAK can target human primary chondrocytes and osteoblast-like cells, in
      addition to synovial fibroblasts. We further demonstrated that TWEAK induced the
      production of matrix metalloproteases in human chondrocytes and potently
      inhibited chondrogenesis and osteogenesis using in vitro models. These results
      provide evidence for a novel cytokine pathway that contributes to joint tissue
      inflammation, angiogenesis, and damage, as well as may inhibit endogenous repair,
      suggesting that TWEAK may be a new therapeutic target for human RA.

PMID- 16888024
TI  - Prostaglandin D2 plays an essential role in chronic allergic inflammation of the
      skin via CRTH2 receptor.
AB  - PGD(2) plays roles in allergic inflammation via specific receptors, the PGD
      receptor designated DP and CRTH2 (chemoattractant receptor homologous molecule
      expressed on Th2 cells). We generated mutant mice carrying a targeted disruption
      of the CRTH2 gene to investigate the functional roles of CRTH2 in cutaneous
      inflammatory responses. CRTH2-deficent mice were fertile and grew normally. Ear
      swelling responses induced by hapten-specific IgE were less pronounced in mutant
      mice, giving 35-55% of the responses of normal mice. Similar results were seen in
      mice treated with a hemopoietic PGD synthase inhibitor, HQL-79, or a CRTH2
      antagonist, ramatroban. The reduction in cutaneous responses was associated with
      decreased infiltration of lymphocytes, eosinophils, and basophils and decreased
      production of macrophage-derived chemokine and RANTES at inflammatory sites. In
      models of chronic contact hypersensitivity induced by repeated hapten
      application, CRTH2 deficiency resulted in a reduction by approximately half of
      skin responses and low levels (63% of control) of serum IgE production, although
      in vivo migration of Langerhans cells and dendritic cells to regional lymph nodes
      was not impaired in CRTH2-deficient mice. In contrast, delayed-type
      hypersensitivity to SRBC and irritation dermatitis in mutant mice were the same
      as in wild-type mice. These findings indicate that the PGD(2)-CRTH2 system plays
      a significant role in chronic allergic skin inflammation. CRTH2 may represent a
      novel therapeutic target for treatment of human allergic disorders, including
      atopic dermatitis.

PMID- 16888025
TI  - Lipoic acid affects cellular migration into the central nervous system and
      stabilizes blood-brain barrier integrity.
AB  - Reactive oxygen species (ROS) play an important role in various events underlying
      multiple sclerosis (MS) pathology. In the initial phase of lesion formation, ROS
      are known to mediate the transendothelial migration of monocytes and induce a
      dysfunction of the blood-brain barrier (BBB). In this study, we describe the
      beneficial effect of the antioxidant alpha-lipoic acid (LA) on these phenomena.
      In vivo, LA dose-dependently prevented the development of clinical signs in a rat
      model for MS, acute experimental allergic encephalomyelitis (EAE). Clinical
      improvement was coupled to a decrease in leukocyte infiltration into the CNS, in
      particular monocytes. Monocytes isolated from the circulation of LA-treated rats
      revealed a reduced migratory capacity to cross a monolayer of rat brain
      endothelial cells in vitro compared with monocytes isolated from untreated EAE
      controls. Using live cell imaging techniques, we visualized and quantitatively
      assessed that ROS are produced within minutes upon the interaction of monocytes
      with brain endothelium. Monocyte adhesion to an in vitro model of the BBB
      subsequently induced enhanced permeability, which could be inhibited by LA.
      Moreover, administration of exogenous ROS to brain endothelial cells induced
      cytoskeletal rearrangements, which was inhibited by LA. In conclusion, we show
      that LA has a protective effect on EAE development not only by affecting the
      migratory capacity of monocytes, but also by stabilization of the BBB, making LA
      an attractive therapeutic agent for the treatment of MS.

PMID- 16888026
TI  - Human mast cell-derived gelatinase B (matrix metalloproteinase-9) is regulated by
      inflammatory cytokines: role in cell migration.
AB  - Mast cells are key effectors in the pathogenesis of inflammatory and tissue
      destructive diseases such as rheumatoid arthritis (RA). These cells contain
      specialized secretory granules loaded with bioactive molecules including
      cytokines, growth factors, and proteases that are released upon activation. This
      study investigated the regulation of matrix metalloproteinase MMP-9 (gelatinase
      B) in human mast cells by cytokines that are known to be involved in the
      pathogenesis of RA. Immunohistochemical staining of synovial tissue showed
      abundant expression of MMP-9 by synovial tissue mast cells in patients with RA
      but not in normal controls. The expression, activity, and production of MMP-9 in
      mast cells was confirmed by RT-PCR, zymography, and Western blotting using cord
      blood-derived human mast cells (CB-HMC). Treatment of CB-HMC with TNF-alpha
      significantly increased the expression of MMP-9 mRNA and up-regulated the
      activity of MMP-9 in a time- and dose-dependent manner. By contrast, IFN-gamma
      inhibited MMP-9 mRNA and protein expression. The cytokine-mediated regulation of
      MMP-9 was also apparent in the human mast cell line (HMC-1) and in mouse bone
      marrow-derived mast cells. Furthermore, TNF-alpha significantly increased the
      invasiveness of CB-HMC across Matrigel-coated membranes while the addition of IFN
      gamma, rTIMP-1, or pharmacological MMP inhibitors significantly reduced this
      process. These observations suggest that MMP-9 is not a stored product in mast
      cells but these cells are capable of producing this enzyme under inflammatory
      conditions that may facilitate the migration of mast cell progenitors to sites of
      inflammation and may also contribute to local tissue damage.

PMID- 16888027
TI  - CCL2 regulates angiogenesis via activation of Ets-1 transcription factor.
AB  - Although recent studies have suggested that CC chemokine CCL2 may directly affect
      the angiogenesis, the signaling events involved in such regulation remain to be
      determined. This study investigated a potential signal mechanism involved in CCL2
      induced angiogenesis. Our in vitro and in vivo (hemangioma model of angiogenesis)
      experiments confirmed earlier findings that CCL2 can induce angiogenesis
      directly. Using a gene array analysis, CCL2 was found to induce expression of
      several angiogenic factors in brain endothelial cells. Among the most prominent
      was an up-regulation in Ets-1 transcription factor. CCL2 induced a significant
      increase in Ets-1 mRNA and protein expression as well as Ets-1 DNA-binding
      activity. Importantly, Ets-1 antisense oligonucleotide markedly abrogated in
      vitro CCL2-induced angiogenesis, suggesting that Ets-1 is critically involved in
      this process. Activation of Ets-1 by CCL2 further regulated some of Ets-1 target
      molecules including beta(3) integrins. CCL2 induced significant up-regulation of
      beta(3) mRNA and protein expression, and this effect of CCL2 was prevented by the
      Ets-1 antisense oligonucleotide. The functional regulation of Ets-1 activity by
      CCL2 was dependent on ERK-1/2 cascade. Inhibition of ERK1/2 activity by PD98509
      prevented CCL2-induced increases in Ets-1 DNA-binding activity and Ets-1 mRNA
      expression. Based on these findings, we suggest that Ets-1 transcription factor
      plays a critical role in CCL2 actions on brain endothelial cells and CCL2-induced
      angiogenesis.

PMID- 16888028
TI  - Papillomavirus-like particles are an effective platform for amyloid-beta
      immunization in rabbits and transgenic mice.
AB  - Immunization with amyloid-beta (Abeta) prevents the deposition of Abeta in the
      brain and memory deficits in transgenic mouse models of Alzheimer's disease (AD),
      opening the possibility for immunotherapy of AD in humans. Unfortunately, the
      first human trial of Abeta vaccination was complicated, in a small number of
      vaccinees, by cell-mediated meningoencephalitis. To develop an Abeta vaccine that
      lacks the potential to induce autoimmune encephalitis, we have generated
      papillomavirus-like particles (VLP) that display 1-9 aa of Abeta protein
      repetitively on the viral capsid surface (Abeta-VLP). This Abeta peptide was
      chosen because it contains a functional B cell epitope, but lacks known T cell
      epitopes. Rabbit and mouse vaccinations with Abeta-VLP were well tolerated and
      induced high-titer autoAb against Abeta, that inhibited effectively assembly of
      Abeta(1-42) peptides into neurotoxic fibrils in vitro. Following Abeta-VLP
      immunizations of APP/presenilin 1 transgenic mice, a model for human AD, we
      observed trends for reduced Abeta deposits in the brain and increased numbers of
      activated microglia. Furthermore, Abeta-VLP vaccinated mice also showed increased
      levels of Abeta in plasma, suggesting efflux from the brain into the vascular
      compartment. These results indicate that the Abeta-VLP vaccine induces an
      effective humoral immune response to Abeta and may thus form a basis to develop a
      safe and efficient immunotherapy for human AD.

PMID- 16888030
TI  - Calcineurin is expressed and plays a critical role in inflammatory arthritis.
AB  - Calcineurin is a calcium-activated phosphatase to mediate lymphocyte activation
      and neuron signaling, but its role in inflammatory arthritis remains largely
      unknown. In this study, we demonstrate that calcineurin was highly expressed in
      the lining layer, infiltrating leukocytes, and endothelial cells of rheumatoid
      synovium. The basal expression levels of calcineurin were higher in the cultured
      synoviocytes of rheumatoid arthritis patients than those of osteoarthritis
      patients. The calcineurin activity in the synoviocytes was increased by the
      stimulation with proinflammatory cytokines such as IL-1beta and TNF-alpha.
      Moreover, rheumatoid arthritis synoviocytes had an enlarged intracellular Ca(2+)
      store and showed a higher degree of [Ca(2+)](i) release for calcineurin activity
      than osteoarthritis synoviocytes when stimulated with either TNF-alpha or phorbol
      myristate acetate. IL-10, an anti-inflammatory cytokine, failed to increase the
      Ca(2+) and calcineurin activity. The targeted inhibition of calcineurin by the
      overexpression of calcineurin-binding protein 1, a natural calcineurin
      antagonist, inhibited the production of IL-6 and matrix metalloproteinase-2 by
      rheumatoid synoviocytes in a similar manner to the calcineurin inhibitor,
      cyclosporin A. Moreover, the abundant calcineurin expression was found in the
      invading pannus in the joints of mice with collagen-induced arthritis. In these
      mice, calcineurin activity in the cultured synovial and lymph node cells
      correlated well with the severity of arthritis, but which was suppressed by
      cyclosporin A treatment. Taken together, our data suggest that the abnormal
      activation of Ca(2+) and calcineurin in the synoviocytes may contribute to the
      pathogenesis of chronic arthritis and thus provide a potential target for
      controlling inflammatory arthritis.

PMID- 16888031
TI  - Monocyte-derived human macrophages mediate anergy in allogeneic T cells and
      induce regulatory T cells.
AB  - Activation of alloreactive T cells by APCs such as dendritic cells (DC) has been
      implicated as crucial step in transplant rejection. In contrast, it has been
      proposed that macrophages (Mphi) maintain tolerance toward alloantigens. It was
      therefore the aim of this study to further analyze the T cell-stimulatory
      capacity of mature DC and Mphi in vitro using the model of allogeneic MLR. There
      was a strong proliferative response in T cells cocultured with DC, which was
      further increased upon restimulation in a secondary MLR. In contrast, T cells did
      not proliferate in cocultures with Mphi despite costimulation with anti-CD28 and
      IL-2. Cytokine analysis revealed considerable levels of IL-10 in cocultures of T
      cells with Mphi, whereas high amounts of IL-2 and IFN-gamma were present in
      cocultures with DC. There was only minimal T cell proliferation in a secondary
      MLR when T cells were rescued from primary MLR with Mphi and restimulated with DC
      of the same donor, or DC of an unrelated donor (third party), whereas a strong
      primary proliferative response was observed in resting T cells, demonstrating
      induction of T cell anergy by Mphi. Functional analysis of T cells rescued from
      cocultures with Mphi demonstrated that anergy was at least partly mediated by IL
      10-producing regulatory T cells induced by Mphi. These results demonstrate that
      Mphi drive the differentiation of regulatory T cells and mediate anergy in
      allogeneic T cells, supporting the concept that Mphi maintain peripheral
      tolerance in vivo.

PMID- 16888029
TI  - Paucity of clinical disease despite serological autoimmunity and kidney pathology
      in lupus-prone New Zealand mixed 2328 mice deficient in BAFF.
AB  - Constitutive overexpression of B cell-activating factor belonging to the TNF
      family (BAFF) promotes development of systemic lupus erythematosus (SLE), and
      treatment of SLE mice with BAFF antagonists ameliorates disease. To determine
      whether SLE can develop de novo in BAFF-deficient hosts, BAFF-deficient New
      Zealand Mixed (NZM) 2328 (NZM.Baff(-/-)) mice were generated. In NZM.Baff(-/-)
      mice, spleen B cells (including CD5(+) B1a and CD5(-) B1b B cells), germinal
      centers, Ig-secreting cells, and T cells were reduced in comparison to
      NZM.Baff(+/+) mice. Serum total Ig and autoantibody levels were reduced at 4-6 mo
      but approached wild-type levels with increasing age, indicating that autoreactive
      B cells can survive and secrete autoantibodies despite the complete absence of
      BAFF. At least some of these autoantibodies are nephrophilic in that glomerular
      deposition of total IgG and IgG1 (but not of IgG2a, IgG2b, or C3) was substantial
      in NZM.Baff(-/-) mice by 12-13 mo of age. Despite proliferative
      glomerulonephritis, highlighted by widespread glomerular hyaline thrombi, being
      common among NZM.Baff(-/-) mice by 6-7 mo of age, severe proteinuria and
      mortality were greatly attenuated. These results demonstrate that the lifelong
      absence of BAFF does not protect NZM 2328 mice from serological autoimmunity and
      renal pathology. Nevertheless, the character of the renal pathology is altered,
      and the mice are largely spared from clinically overt disease (severe proteinuria
      and premature death). These observations may have profound ramifications for the
      use of BAFF antagonists in human SLE and related diseases.

PMID- 16888032
TI  - Increased levels of soluble CD40L in African tick bite fever: possible
      involvement of TLRs in the pathogenic interaction between Rickettsia africae,
      endothelial cells, and platelets.
AB  - The pathophysiological hallmark of spotted fever group rickettsioses comprises
      infection of endothelial cells with subsequent infiltration of inflammatory
      cells. Based on its ability to promote inflammation and endothelial cell
      activation, we investigated the role of CD40L in African tick bite fever (ATBF),
      caused by Rickettsia africae, using different experimental approaches. Several
      significant findings were revealed. 1) Patients with ATBF (n = 15) had increased
      serum levels of soluble CD40 ligand (sCD40L), which decreased during follow-up.
      2) These enhanced sCD40L levels seem to reflect both direct and indirect (through
      endothelial cell activation involving CX3CL1-related mechanisms) effects of R.
      africae on platelets. 3) In combination with sCD40L, R. africae promoted a
      procoagulant state in endothelial cells by up-regulating tissue factor and down
      regulating thrombomodulin expression. 4) Although the R. africae-mediated
      activation of platelets involved TLR2, the combined procoagulant effects of R.
      africae and sCD40L on endothelial cells involved TLR4. 5) Doxycycline
      counteracted the combined procoagulant effects of R. africae and sCD40L on
      endothelial cells. Our findings suggest an inflammatory interaction between
      platelets and endothelial cells in ATBF, involving TLR-related mechanisms. This
      interaction, which includes additive effects between sCD40L and R. africae, may
      contribute to endothelial inflammation and hypercoagulation in this disorder.

PMID- 16888033
TI  - The antineoplastic agent bryostatin-1 differentially regulates IFN-gamma receptor
      subunits in monocytic cells: transcriptional and posttranscriptional control of
      IFN-gamma R2.
AB  - Bryostatin-1 (Bryo-1) is a potent ligand and modulator of protein kinase C that
      exerts antineoplastic and immunomodulatory activities both in vitro and in vivo.
      We have previously reported that Bryo-1 synergized with IFN-gamma to induce NO
      synthase and NO by macrophages. To determine whether this effect was associated
      with changes in levels of IFN-gammaR, we investigated the effects of Bryo-1 on
      the expression and regulation of IFN-gammaR chains in monocytic cells. Northern
      blot analysis revealed that Bryo-1 treatment of the human monocytic cell lines
      MonoMac6 and THP-1 and human monocytes enhanced the expression of IFN-gammaR2
      mRNA but did not affect IFN-gammaR1 mRNA expression. Bryo-1 increased IFN-gammaR2
      mRNA in a dose-dependent manner as early as 3 h posttreatment. Bryo-1-induced up
      regulation of IFN-gammaR2 mRNA levels is not dependent on de novo protein
      synthesis as shown by cell treatment with the protein-synthesis inhibitor
      cycloheximide. Bryo-1 treatment increased the IFN-gammaR2 mRNA half-life by 2 h.
      EMSA analysis from Bryo-1-treated MonoMac6 cells showed an increased nuclear
      protein binding to the NF-kappaB motif present in the 5' flanking region of the
      human IFN-gammaR2 promoter that was markedly decreased by pretreatment with the
      NF-kappaB inhibitor SN50. These results show for the first time that Bryo-1 up
      regulates IFN-gammaR2 expression in monocytic cells. Given the pivotal role that
      IFN-gamma exerts on monocyte activation and in the initiation and outcome of the
      immune response, the induction of IFN-gammaR2 by Bryo-1 has significant
      implications in immunomodulation and could overcome some of the immune defects
      observed in cancer patients.

PMID- 16888034
TI  - Spontaneous CD4+ T cell responses against TRAG-3 in patients with melanoma and
      breast cancers.
AB  - The taxol resistance gene TRAG-3 was initially isolated from cancer cell lines
      that became resistant to taxol in vitro. TRAG-3 is a cancer germline Ag expressed
      by tumors of different histological types including the majority of melanoma,
      breast, and lung cancers. In the present study, we report that patients with
      stage IV melanoma and breast cancers developed spontaneous IFN-gamma-producing
      CD4+ T cell responses against a single immunodominant and promiscuous peptide
      epitope from TRAG-3 presented in the context of multiple HLA-DR molecules. The
      TRAG-3-specific CD4+ T cells and clones were expanded in vitro and recognized not
      only peptide pulsed APCs but also autologous dendritic cells (DCs) loaded with
      the TRAG-3 protein. All stage IV melanoma patients with TRAG-3-expressing tumors
      developed spontaneous CD4+ T cell responses against TRAG-3, demonstrating its
      strong immunogenicity. None of these patients had detectable IgG Ab responses
      against TRAG-3. TCRbeta gene usage studies of TRAG-3-specific CD4+ T cell clones
      from a melanoma patient and a normal donor suggested a restricted TCR repertoire
      in patients with TRAG-3-expressing tumors. Altogether, our data define a novel
      profile of spontaneous immune responses to cancer germline Ag-expressing tumors,
      showing that spontaneous TRAG-3-specific CD4+ T cells are directed against a
      single immunodominant epitope and exist independently of Ab responses. Because of
      its immunodominance, peptide TRAG-3(34-48) is of particular interest for the
      monitoring of spontaneous immune responses in patients with TRAG-3-expressing
      tumors and for the development of cancer vaccines.

PMID- 16888035
TI  - Melanoma growth is reduced in fat-1 transgenic mice: impact of omega-6/omega-3
      essential fatty acids.
AB  - An important nutritional question as to whether the ratio of omega-6 (n-6) to
      omega-3 (n-3) fatty acids plays a role in tumorigenesis remains to be clarified
      in well qualified experimental models. The recently engineered fat-1 mice, which
      can convert n-6 to n-3 fatty acids and have a balanced ratio of n-6 to n-3 fatty
      acids in their tissues and organs independent of diet, allow carefully controlled
      studies to be performed in the absence of potential confounding factors of diet
      and therefore are a useful model for elucidating the role of n-6/n-3 fatty acid
      ratio in tumorigenesis. We implanted mouse melanoma B16 cells into transgenic and
      WT littermates and examined the incidence of tumor formation and tumor growth
      rate. The results showed a dramatic reduction of melanoma formation and growth in
      fat-1 transgenic mice. The level of n-3 fatty acids and their metabolite
      prostaglandin E(3) (PGE(3)) were much higher (but the n-6/n-3 ratio is much
      lower) in the tumor and surrounding tissues of fat-1 mice than that of WT
      animals. The phosphatase and tensin homologue deleted on the chromosome 10 (PTEN)
      gene was significantly up-regulated in the fat-1 mice. In vitro experiments
      showed that addition of the n-3 fatty acid eicosapentaenoic acid or PGE(3)
      inhibited the growth of B16 cell line and increased the expression of PTEN, which
      could be partially attenuated by inhibition of PGE(3) production, suggesting that
      PGE(3) may act as an antitumor mediator. These data demonstrate an anticancer
      (antimelanoma) effect of n-3 fatty acids through, at least in part, activation of
      PTEN pathway mediated by PGE(3).

PMID- 16888036
TI  - A picornavirus protein interacts with Ran-GTPase and disrupts nucleocytoplasmic
      transport.
AB  - Active nucleocytoplasmic transport of protein and RNA in eukaryotes depends on
      the Ran-GTPase system to regulate cargo-receptor interactions. Several viruses,
      including the RNA picornaviruses, encode factors that alter nuclear transport
      with the aim of suppressing synthesis of antiviral factors and promoting viral
      replication. Picornaviruses in the cardiovirus genus express a unique 67-aa
      Leader protein (L), known to alter the subcellular distribution of IFN regulatory
      proteins targeted to the nucleus. We report here that L binds directly to Ran and
      blocks nuclear export of new mRNAs. In Xenopus egg extracts, recombinant L also
      inhibits mitotic spindle assembly, a RanGTP function crucial to cell-cycle
      progression. We propose that L inhibits nucleocytoplasmic transport during
      infection by disrupting the RanGDP/GTP gradient. This inhibition triggers an
      efflux of nuclear proteins necessary for viral replication and causes IFN
      suppression. To our knowledge, L is the first viral picornaviral protein to
      interact directly with Ran and modulate the Ran-dependent nucleocytoplasmic
      pathway.

PMID- 16888037
TI  - Lateral positioning at the dorsal midline: Slit and Roundabout receptors guide
      Drosophila heart cell migration.
AB  - Heart morphogenesis requires the coordinated regulation of cell movements and
      cell-cell interactions between distinct populations of cardiac precursor cells.
      Little is known about the mechanisms that organize cardiac cells into this
      complex structure. In this study, we analyzed the role of Slit, an extracellular
      matrix protein and its transmembrane receptors Roundabout (Robo) and Roundabout2
      (Robo2) during morphogenesis of the Drosophila heart tube, a process analogous to
      early heart formation in vertebrates. During heart assembly, two types of
      progenitor cells align into rows and coordinately migrate to the dorsal midline
      of the embryo, where they merge to assemble a linear heart tube. Here we show
      that cardiac-specific expression of Slit is required to maintain adhesion between
      cells within each row during dorsal migration. Moreover, differential Robo
      expression determines the relative distance each row is positioned from the
      dorsal midline. The innermost CBs express only Robo, whereas the flanking
      pericardial cells express both receptors. Removal of robo2 causes pericardial
      cells to shift toward the midline, whereas ectopic robo2 in CBs drives them
      laterally, resulting in an unfused heart tube. We propose a model in which Slit
      has a dual role during assembly of the linear heart tube, functioning to regulate
      both cell positioning and adhesive interactions between migrating cardiac
      precursor cells.

PMID- 16888038
TI  - Memory enhancement in healthy older adults using a brain plasticity-based
      training program: a randomized, controlled study.
AB  - Normal aging is associated with progressive functional losses in perception,
      cognition, and memory. Although the root causes of age-related cognitive decline
      are incompletely understood, psychophysical and neuropsychological evidence
      suggests that a significant contribution stems from poorer signal-to-noise
      conditions and down-regulated neuromodulatory system function in older brains.
      Because the brain retains a lifelong capacity for plasticity and adaptive
      reorganization, dimensions of negative reorganization should be at least
      partially reversible through the use of an appropriately designed training
      program. We report here results from such a training program targeting age
      related cognitive decline. Data from a randomized, controlled trial using
      standardized measures of neuropsychological function as outcomes are presented.
      Significant improvements in assessments directly related to the training tasks
      and significant generalization of improvements to nonrelated standardized
      neuropsychological measures of memory (effect size of 0.25) were documented in
      the group using the training program. Memory enhancement appeared to be sustained
      after a 3-month no-contact follow-up period. Matched active control and no
      contact control groups showed no significant change in memory function after
      training or at the 3-month follow-up. This study demonstrates that intensive,
      plasticity-engaging training can result in an enhancement of cognitive function
      in normal mature adults.

PMID- 16888039
TI  - The significance of direct sunlight and polarized skylight in the ant's celestial
      system of navigation.
AB  - As textbook knowledge has it, bees and ants use polarized skylight as a backup
      cue whenever the main compass cue, the sun, is obscured by clouds. Here we show,
      by employing a unique experimental paradigm, that the celestial compass system of
      desert ants, Cataglyphis, relies predominantly on polarized skylight. If ants
      experience only parts of the polarization pattern during training but the full
      pattern in a subsequent test situation, they systematically deviate from their
      true homeward courses, with the systematics depending on what parts of the
      skylight patterns have been presented during training. This "signature" of the
      polarization compass remains unaltered, even if the ants can simultaneously
      experience the sun, which, if presented alone, enables the ants to select their
      true homeward courses. Information provided by direct sunlight and polarized
      skylight is picked up by different parts of the ant's compound eyes and is
      channeled into two rather separate systems of navigation.

PMID- 16888040
TI  - Microfluidic vias enable nested bioarrays and autoregulatory devices in Newtonian
      fluids.
AB  - We report on a fundamental technological advance for multilayer
      polydimethylsiloxane (PDMS) microfluidics. Vertical passages (vias), connecting
      channels located in different layers, are fabricated monolithically, in parallel,
      by simple and easy means. The resulting 3D connectivity greatly expands the
      potential complexity of microfluidic architecture. We apply the vias to printing
      nested bioarrays and building autoregulatory devices. A current source is
      demonstrated, while a diode and a rectifier are derived; all are building blocks
      for analog circuitry in Newtonian fluids. We also describe microfluidic septa and
      their applications. Vias lay the foundation for a new generation of microfluidic
      devices.

PMID- 16888042
TI  - beta2-Adrenergic receptor downregulation and performance decrements during high
      intensity resistance exercise overtraining.
AB  - Previous research on overtraining due to excessive use of maximal resistance
      exercise loads [100% 1 repetition maximum (1 RM)] indicates that peripheral
      muscle maladaptation contributes to overtraining-induced performance decrements.
      This study examined the cellular and molecular responses of skeletal muscle to
      performance decrements due to high-relative-intensity (%1 RM) resistance exercise
      overtraining. Weight-trained men were divided into overtrained (OT, n = 8) and
      control (Con, n = 8) groups. The OT group performed 10 x 1 at 100% 1 RM daily for
      2 wk, whereas the Con group performed normal training 2 days/wk. Muscle biopsies
      from the vastus lateralis muscle, voluntary static and dynamic muscle
      performances, and nocturnal urinary epinephrine were assessed before (pre) and
      after (post) overtraining. Overtraining occurred as indicated by a decrease in 1
      RM strength for the OT group (mean +/- SE; OT pre = 159.3 +/- 10.1 kg, OT post =
      151.4 +/- 9.9 kg, Con pre = 146.0 +/- 12.9 kg, Con post = 144.9 +/- 13.3 kg), as
      well as a 36.3% decrease in mean power at 100% 1-RM loads. Normal training could
      be resumed only after 2-8 wk of training cessation. Muscle beta(2)-adrenergic
      receptor (beta(2)-AR; fmol/mg protein) density significantly decreased by 37.0%
      for the OT group and was unchanged for the Con group (-1.8%). Nocturnal urinary
      epinephrine for the OT group increased by 49%, although this was not significant
      (effect size = 0.42). The ratio of nocturnal urinary epinephrine to beta(2)-AR
      density suggested a decreased beta(2)-AR sensitivity for the OT group (2.4-fold
      increase). Overtraining occurred based on decreased muscular force and power.
      Desensitization of the beta(2)-AR system suggests that this may be an important
      contributor to performance decrements due to excessive use of maximal resistance
      exercise loads.

PMID- 16888043
TI  - Effect of carbon dioxide on neonatal mouse lung: a genomic approach.
AB  - Despite the deleterious effects associated with elevated carbon dioxide (CO(2))
      or hypercapnia, it has been hypothesized that CO(2) can protect the lung from
      injury. However, the effects of chronic hypercapnia on the neonatal lung are
      unknown. Hence, we investigated the effect of chronic hypercapnia on neonatal
      mouse lung to identify genes that could potentially contribute to hypercapnia
      mediated lung protection. Newborn mouse litters were exposed to 8% CO(2), 12%
      CO(2), or room air for 2 wk. Lungs were excised and analyzed for morphometric
      alterations. The alveolar walls of CO(2)-exposed mice appeared thinner than those
      of controls. Analyses of gene expression differences by microarrays revealed that
      genes from a variety of functional categories were differentially expressed
      following hypercapnia treatment, including those encoding growth factors,
      chemokines, cytokines, and endopeptidases. In particular and of major interest,
      the expression level of genes encoding surfactant proteins A and D, as well as
      chloride channel calcium-activated 3, were significantly increased, but the
      expression of WNT1-inducible signaling pathway protein 2 was significantly
      decreased. The significant changes in gene expression occurred mostly at 8%
      CO(2), but only a few at 12% CO(2). Our results lead us to conclude that 1) there
      are a number of gene families that may contribute to hypercapnia-mediated lung
      protection; 2) the upregulation of surfactant proteins A and D may play a role as
      anti-inflammatory or antioxidant agents; and 3) the effects of CO(2) seem to
      depend on the level to which the lung is exposed.

PMID- 16888041
TI  - Molecular model of a type III secretion system needle: Implications for host-cell
      sensing.
AB  - Type III secretion systems are essential virulence determinants for many Gram
      negative bacterial pathogens. The type III secretion system consists of
      cytoplasmic, transmembrane, and extracellular domains. The extracellular domain
      is a hollow needle protruding above the bacterial surface and is held within a
      basal body that traverses both bacterial membranes. Effector proteins are
      translocated, via this external needle, directly into host cells, where they
      subvert normal cell functions to aid infection. Physical contact with host cells
      initiates secretion and leads to formation of a pore, thought to be contiguous
      with the needle channel, in the host-cell membrane. Here, we report the crystal
      structure of the Shigella flexneri needle subunit MxiH and a complete model for
      the needle assembly built into our three-dimensional EM reconstruction. The
      model, combined with mutagenesis data, reveals that signaling of host-cell
      contact is relayed through the needle via intersubunit contacts and suggests a
      mode of binding for a tip complex.

PMID- 16888045
TI  - Responses to mild cold stress are predicted by different individual
      characteristics in young and older subjects.
AB  - Older individuals' ability to maintain core temperature during cold stress is
      impaired; however, the relative importance of individual characteristics that
      influence this response are unknown. The purpose of this study was to determine
      the relative influence of individual characteristics on core temperature and
      tissue insulation (I(t)) during mild cold stress. Forty-two young (23 +/- 1 yr,
      range 18-30 yr) and 46 older (71 +/- 1 yr, range 65-89 yr) subjects, varying
      widely in muscularity, adiposity, and body size, underwent a transient cooling
      protocol during which esophageal temperature (T(es)) was measured continuously
      and I(t) was calculated using standard equations. Multiple-regression analyses
      were performed to determine predictors of T(es) and I(t), and standardized
      regression coefficients were analyzed to determine the relative influence of each
      predictor. Candidate predictors included age, sex, weight, body surface area,
      body surface area-to-mass ratio, sum of skinfolds, percent fat, appendicular
      skeletal muscle mass, and thyroid hormone concentrations (triiodothyronine,
      thyronine). The sum of skinfolds explained 67% (P < 0.01) of the T(es) variance
      in young subjects vs. 2% (P = 0.30) in older subjects. Conversely, appendicular
      skeletal muscle mass explained a greater portion of the variance in older
      subjects for both T(es) (older: 28%, P < 0.01; young: 8%, not significant) and
      I(t) (older: 46%, P < 0.01; young: 17%, P < 0.01). The T(es) residual variance
      was considerably larger in older subjects (59-72% vs. 14-42% in young subjects),
      possibly due to varying rates of physiological aging. These results suggest that
      the relative influence of individual characteristics changes with aging.

PMID- 16888046
TI  - Growth hormone and muscle function responses to skeletal muscle ischemia.
AB  - We examined the effects of ischemia (ISC) alone and with low-intensity exercise
      (ISC+EX) on growth hormone (GH) and muscle function responses. Nine men (22 +/-
      0.7 yr) completed 3 study days: an ISC day (thigh cuff inflated five times, 5 min
      on, 3 min off), an ISC+EX day [knee extension at 20% maximal voluntary
      contraction (MVC) with ISC], and a control day. MVCs and submaximal contraction
      tasks (15 and 30% MVC) were performed before and following the perturbations.
      Surface electromyogram signals were collected from thigh muscles and analyzed for
      median frequency and root mean square alterations. Blood samples were collected
      every 10 min (190 min total) and analyzed for GH concentrations. Peak GH
      concentrations and GH area under the curve were highest (P < 0.01) on the ISC+EX
      day (7.5 microg/l and 432 microg.l(-1).min(-1), respectively) compared with the
      ISC (0.9 microg/l and 76.4 microg.l(-1).min(-1)), and CON (1.1 microg/l and 83.8
      microg.l(-1).min(-1)) days. A greater GH pulse amplitude, mass/pulse, and
      production rate were also observed on the ISC+EX day (P < 0.05). Following the
      intervention, force production decreased on the ISC and ISC+EX days by 16.1 and
      55.8%, respectively, and did not return to baseline values within 5 min of
      recovery. During the submaximal contractions, median frequency shifted to lower
      frequencies for most of the muscles examined, and root mean square electromyogram
      was consistently elevated for ISC+EX day. In conclusion, ISC coupled with
      resistance exercise acutely increases GH levels and reduces MVC, whereas ISC
      alone decreases force capacity, without alterations in GH levels.

PMID- 16888047
TI  - Changes in muscle coordination with training.
AB  - Three core concepts, activity-dependent coupling, the composition of muscle
      synergies, and Hebbian adaptation, are discussed with a view to illustrating the
      nature of the constraints imposed by the organization of the central nervous
      system on the changes in muscle coordination induced by training. It is argued
      that training invoked variations in the efficiency with which motor actions can
      be generated influence the stability of coordination by altering the potential
      for activity-dependent coupling between the cortical representations of the focal
      muscles recruited in a movement task and brain circuits that do not contribute
      directly to the required behavior. The behaviors that can be generated during
      training are also constrained by the composition of existing intrinsic muscle
      synergies. In circumstances in which attempts to produce forceful or high
      velocity movements would otherwise result in the generation of inappropriate
      actions, training designed to promote the development of control strategies
      specific to the desired movement outcome may be necessary to compensate for
      protogenic muscle recruitment patterns. Hebbian adaptation refers to processes
      whereby, for neurons that release action potentials at the same time, there is an
      increased probability that synaptic connections will be formed. Neural
      connectivity induced by the repetition of specific muscle recruitment patterns
      during training may, however, inhibit the subsequent acquisition of new skills.
      Consideration is given to the possibility that, in the presence of the
      appropriate sensory guidance, it is possible to gate Hebbian plasticity and to
      promote greater subsequent flexibility in the recruitment of the trained muscles
      in other task contexts.

PMID- 16888048
TI  - A simple technique to characterize proximal and peripheral nitric oxide exchange
      using constant flow exhalations and an axial diffusion model.
AB  - The most common technique employed to describe pulmonary gas exchange of nitric
      oxide (NO) combines multiple constant flow exhalations with a two-compartment
      model (2CM) that neglects 1) the trumpet shape (increasing surface area per unit
      volume) of the airway tree and 2) gas phase axial diffusion of NO. However,
      recent evidence suggests that these features of the lungs are important
      determinants of NO exchange. The goal of this study is to present an algorithm
      that characterizes NO exchange using multiple constant flow exhalations and a
      model that considers the trumpet shape of the airway tree and axial diffusion
      (model TMAD). Solution of the diffusion equation for the TMAD for exhalation
      flows >100 ml/s can be reduced to the same linear relationship between the NO
      elimination rate and the flow; however, the interpretation of the slope and the
      intercept depend on the model. We tested the TMAD in healthy subjects (n = 8)
      using commonly used and easily performed exhalation flows (100, 150, 200, and 250
      ml/s). Compared with the 2CM, estimates (mean +/- SD) from the TMAD for the
      maximum airway flux are statistically higher (J'aw(NO) = 770 +/- 470 compared
      with 440 +/- 270 pl/s), whereas estimates for the steady-state alveolar
      concentration are statistically lower (CA(NO) = 0.66 +/- 0.98 compared with 1.2
      +/- 0.80 parts/billion). Furthermore, CA(NO) from the TMAD is not different from
      zero. We conclude that proximal (airways) NO production is larger than previously
      predicted with the 2CM and that peripheral (respiratory bronchioles and alveoli)
      NO is near zero in healthy subjects.

PMID- 16888049
TI  - H1 and H2 receptors mediate postexercise hyperemia in sedentary and endurance
      exercise-trained men and women.
AB  - In sedentary individuals, H(1) receptors mediate the early portion of
      postexercise skeletal muscle hyperemia, whereas H(2) receptors mediate the later
      portion. It is not known whether postexercise hyperemia also presents in
      endurance-trained individuals. We hypothesized that the postexercise skeletal
      muscle hyperemia would also exist in endurance-trained individuals and that
      combined blockade of H(1) and H(2) receptors would abolish the long-lasting
      postexercise hyperemia in trained and sedentary individuals. We studied 28
      sedentary and endurance trained men and women before and through 90 min after a
      60-min bout of cycling at 60% peak O(2) uptake on control and combined H(1)- and
      H(2)-receptor antagonist days (fexofenadine and ranitidine). We measured arterial
      pressure (brachial auscultation) and femoral blood flow (Doppler ultrasound). On
      the control day, femoral vascular conductance (calculated as flow/pressure) was
      elevated in all groups 60 min after exercise (sedentary men: Delta86 +/- 35%,
      trained men, Delta65 +/- 18%; sedentary women, Delta61 +/- 19%, trained women:
      Delta59 +/- 23%, where Delta is change; all P < 0.05 vs. preexercise). In
      contrast, on the histamine antagonist day, femoral vascular conductance was not
      elevated in any of the groups after exercise (sedentary men: Delta21 +/- 17%,
      trained men: Delta9 +/- 5%, sedentary women: Delta19 +/- 4%, trained women:
      Delta11 +/- 11%; all P > 0.16 vs. preexercise; all P < 0.05 vs. control day).
      These data suggest postexercise skeletal muscle hyperemia exists in endurance
      trained men and women. Furthermore, histaminergic mechanisms produce the long
      lasting hyperemia in sedentary and endurance-trained individuals.

PMID- 16888050
TI  - Oxygen pressures in the interstitial space and their relationship to those in the
      blood plasma in resting skeletal muscle.
AB  - This study compared oxygen pressures (Po(2)), measured by oxygen-dependent
      quenching of phosphorescence, in the intravascular (blood plasma) space in the
      muscle with those in the interstitial (pericellular) space. Our hypothesis was
      that the capillary wall would not significantly impede oxygen diffusion from the
      blood plasma to the pericellular space. A new near-infrared oxygen sensitive
      probe, Oxyphor G3, was used to obtain oxygen distributions in the interstitial
      space. Oxyphor G3 is a Pd-tetrabenzoporphyrin encapsulated inside generation 2
      poly-arylglycine (AG) dendrimer. The periphery of the dendrimer is modified with
      oligoethylene glycol residues (average molecular weight 350) to make the probe
      water soluble and biologically inert. Oxyphor G3 was injected into thigh muscle
      using a 30-gauge needle. Histograms of the Po(2) in the interstitial space were
      measured in awake and anesthetized animals and compared with those for Oxyphor G2
      in the intravascular (blood plasma) space. For awake mice, the lowest 10% of
      Po(2) values for the interstitial and intravascular spaces (believed to represent
      capillary bed) were not significantly different [23.8 (SD 4.5) and 25 Torr (SD
      4.3), respectively], whereas, in isoflurane-anesthetized mice, there was a small
      but significant (P = 0.01) difference [20.4 (SD 6.3) and 27.9 Torr (SD 3.5),
      respectively]. The peak values for the histograms for the interstitial space in
      awake and isoflurane-anesthetized mice were 40.8 (SD 7.5) and 36.9 Torr (SD 8.3),
      respectively, whereas those for the intravascular space were 52.2 (SD 4.9) and
      55.9 Torr (SD 8.4), respectively, showing no significant difference due to
      isoflurane anesthesia. The histograms for the intravascular space were
      significantly wider, with more contribution at higher Po(2) values. A different
      anesthetic, ketamine plus xylazine injected intraperitoneally, caused a marked
      decrease in the tissue Po(2) values in both spaces, with the time course and
      extent of the decrease dependent on the time after injection and variable among
      mice. It was, therefore, not further used.

PMID- 16888051
TI  - Microarray analysis of the tendinopathic rat supraspinatus tendon: glutamate
      signaling and its potential role in tendon degeneration.
AB  - Degenerative tendon injury or "tendinopathy" is one of the most common disorders
      of the musculoskeletal system. We used a rat model (Soslowsky LJ, Thomopoulos S,
      Tun S, Flanagan CL, Keefer CC, Mastaw J, and Carpenter JE. J Shoulder Elbow Surg
      9: 79-84, 2000) to identify novel gene expression in the exercised-induced
      degenerated supraspinatus tendon by microarray and real-time PCR analyses. We
      identified several novel groups of differentially expressed genes, including
      those involved in apoptosis and related stress responses, and also genes that
      appear to be involved in glutamate signaling in tendon tissue, similar to recent
      findings by us in a microarray study of healing in the transected Achilles tendon
      of the rat (24). Until recently this kind of cellular communication was thought
      only to exist in cells of the central nervous system (CNS), where it is vital for
      CNS function. We further show that glutamate appears to induce a proapoptotic
      response in cultured tendon cells, similar to the "excitotoxic" response of cells
      in the CNS that become overstimulated. This may prove to be at least a partial
      cause of degeneration in overused tendon tissue and allow the development of
      treatments or "prehibilitation" regimens for tendinopathy based on currently used
      non-toxic glutamate antagonists.

PMID- 16888052
TI  - Acute lung injury augments hypoxic ventilatory response in the absence of
      systemic hypoxemia.
AB  - The objective of the present study was to examine the impact of early stages of
      lung injury on ventilatory control by hypoxia and hypercapnia. Lung injury was
      induced with intratracheal instillation of bleomycin (BM; 1 unit) in adult, male
      Sprague-Dawley rats. Control animals underwent sham surgery with saline
      instillation. Five days after the injections, lung injury was present in BM
      treated animals as evidenced by increased neutrophils and protein levels in
      bronchoalveolar lavage fluid, as well as by changes in lung histology and
      computed tomography images. There was no evidence of pulmonary fibrosis, as
      indicated by lung collagen content. Basal core body temperature, arterial Po(2),
      and arterial Pco(2) were comparable between both groups of animals. Ventilatory
      responses to hypoxia (12% O(2)) and hypercapnia (7% CO(2)) were measured by whole
      body plethysmography in unanesthetized animals. Baseline respiratory rate and the
      hypoxic ventilatory response were significantly higher in BM-injected compared
      with control animals (P = 0.003), whereas hypercapnic ventilatory response was
      not statistically different. In anesthetized, spontaneously breathing animals,
      response to brief hyperoxia (Dejours' test, an index of peripheral chemoreceptor
      sensitivity) and neural hypoxic ventilatory response were augmented in BM-exposed
      relative to control animals, as measured by diaphragmatic electromyelograms. The
      enhanced hypoxic sensitivity persisted following bilateral vagotomy, but was
      abolished by bilateral carotid sinus nerve transection. These data demonstrate
      that afferent sensory input from the carotid body contributes to a selective
      enhancement of hypoxic ventilatory drive in early lung injury in the absence of
      pulmonary fibrosis and arterial hypoxemia.

PMID- 16888053
TI  - A critical understanding of the fractal model of metabolic scaling.
AB  - The exponent of the scaling of metabolic rate with body mass has been the subject
      of debate for more than a century. The argument is at two levels, one concerning
      questions of empirical support for the exponent and the other, how to derive it
      theoretically. At this second level, the exponent is usually treated as the
      outcome of an underlying physical burden and approached as the search for a
      natural law emerging within energetic and geometric constraints. Recently, a
      model relying on fractal geometry was proposed as a general explanation for the
      phenomenon. In the present study, a reanalysis of the fractal model is performed
      to verify its validity. All the conditions that allow for the connection between
      the geometric proposition and the allometric exponent are evaluated, as well as
      the energy loss minimization procedure put forward in the model. It is
      demonstrated that the minimization procedure is mathematically incorrect and ill
      posed. Also, it is shown that none of the connecting conditions are fulfilled.
      Therefore, it is concluded that the fractal model lacks self-consistency and
      correct statement: it relies on strong assumptions of homogeneity in morpho
      physiological features among organisms instead of demonstrating them, as claimed
      by its authors. It is proposed that empiricists and theoreticians should rather
      evaluate the frameworks for addressing metabolic scaling phenomena.

PMID- 16888054
TI  - Effect of parental age and associated size on fecundity, growth and survival in
      the yellow seahorse Hippocampus kuda.
AB  - Seahorses, together with the pipefishes (Family Syngnathidae), are the only
      vertebrates in which embryonic development takes place within a specialised body
      compartment, the brood pouch, of the male instead of the female. Embryos develop
      in close association with the brood pouch epithelium in a manner that bears some
      resemblance to embryo-placental relationships in mammals. We have explored the
      hypothesis that parental body size and age should affect offspring postnatal
      growth and survival if brood pouch quality impacts upon prenatal embryonic
      nutrition or respiration. Using an aquarium population of the yellow seahorse,
      Hippocampus kuda, we show here that large parents produce offspring whose initial
      postnatal growth rates (weeks one to three) were significantly higher than those
      of the offspring of younger and smaller parents. Whereas 90% of offspring from
      the larger parents survived for the duration of the study (7 weeks), less that
      50% of offspring from smaller parents survived for the same period. For the
      offspring of large parents, growth rates from individual males were negatively
      correlated with the number of offspring in the cohort (r=-0.82; P<0.05); this was
      not the case for offspring from small parents (r=0.048; P>0.9). Observations of
      embryos within the pouch suggested that when relatively few embryos are present
      they may attach to functionally advantageous sites and thus gain physiological
      support during gestation. These results suggest that male body size, and pouch
      size and function, may influence the future fitness and survival of their
      offspring.

PMID- 16888055
TI  - Seasonal modulation of sickness behavior in free-living northwestern song
      sparrows (Melospiza melodia morphna).
AB  - A variety of vertebrate species modulate immune function on a seasonal basis to
      cope with seasonal energy deficits and competing life-history demands, such as
      reproduction. Most studies to date have focused upon seasonal variation of
      cellular and humoral immunity, while neglecting behavioral responses to
      infection. These behavioral strategies are collectively termed sickness behaviors
      and are hypothesized to divert energy away from normal activities to combat and
      overcome infection. Sickness behavior can be triggered experimentally by
      injecting bacterial lipopolysaccharide (LPS). In this study, we provide the first
      evidence for seasonal modulation of sickness behavior in a free-living animal.
      Male song sparrows of western Washington state (Melospiza melodia morphna) are
      sedentary and territorial year round, except for a brief time during molt.
      Treatment with LPS decreased territorial aggressive behavior of males in the
      winter (nonbreeding), but not in the spring (breeding). Subjects were recaptured
      approx. 25 h after treatment. Recaptured LPS males in the winter lost more body
      mass than saline-injected controls while LPS males in the spring did not. These
      data indicate that birds in breeding condition were relatively insensitive to the
      effects of LPS. On a proximate level, suppression of sickness behavior during
      breeding is likely mediated by seasonal differences in energy allocation, as
      wintering sparrows were significantly heavier and had larger subcutaneous fat
      reserves and lower baseline corticosterone levels than breeding birds.
      Ultimately, suppression of sickness behavior may represent an allocation strategy
      to balance current reproductive opportunities with the life-history costs of self
      defense.

PMID- 16888056
TI  - Identification of two cationic amino acid transporters required for nutritional
      signaling during mosquito reproduction.
AB  - The defining characteristic of anautogenous mosquitoes is their requirement for a
      blood meal to initiate reproduction. The need for blood drives the association of
      vector and host, and is the primary reason why anautogenous mosquitoes are
      effective disease vectors. During mosquito vitellogenesis, a key process in
      reproduction, yolk protein precursor (YPP) gene expression is activated
      specifically in the fat body, the insect analogue of the vertebrate liver. We
      have demonstrated that blood meal derived amino acids (AAs) activate YPP genes
      via the target of rapamycin (TOR)-signal transduction pathway. Here we show, by
      stimulating fat bodies with balanced AA solutions lacking individual AAs, that
      specific cationic and branched AAs are essential for activation of the
      vitellogenin (vg) gene, the major YPP gene. Treatment of fat bodies with AA
      uptake inhibitors results in a strong inhibition of AA-induced vg gene expression
      proving that an active transport mechanism is necessary to transduce the AA
      signal. We identified two cationic AA transporters (CATs) in the fat body of
      Aedes aegypti females--Aa slimfast and iCAT2. RNAi knockdown of slimfast and
      iCAT2 results in a strong decrease in the response to AAs by the vg gene similar
      to that seen due to TOR inhibition. These data demonstrate that active uptake of
      specific AAs plays a key role in nutritional signaling during the onset of
      vitellogenic gene expression in mosquitoes and it is mediated by two cationic AA
      transporters.

PMID- 16888057
TI  - Beauty in the eye of the beholder: the two blue opsins of lycaenid butterflies
      and the opsin gene-driven evolution of sexually dimorphic eyes.
AB  - Although previous investigations have shown that wing coloration is an important
      component of social signaling in butterflies, the contribution of opsin evolution
      to sexual wing color dichromatism and interspecific divergence remains largely
      unexplored. Here we report that the butterfly Lycaena rubidus has evolved
      sexually dimorphic eyes due to changes in the regulation of opsin expression
      patterns to match the contrasting life histories of males and females. The L.
      rubidus eye contains four visual pigments with peak sensitivities in the
      ultraviolet (UV; lambdamax=360 nm), blue (B; lambdamax=437 nm and 500 nm,
      respectively) and long (LW; lambdamax=568 nm) wavelength range. By combining in
      situ hybridization of cloned opsin-encoding cDNAs with epi
      microspectrophotometry, we found that all four opsin mRNAs and visual pigments
      are expressed in the eyes in a sex-specific manner. The male dorsal eye, which
      contains only UV and B (lambdamax=437 nm) visual pigments, indeed expresses two
      short wavelength opsin mRNAs, UVRh and BRh1. The female dorsal eye, which also
      has the UV and B (lambdamax=437 nm) visual pigments, also contains the LW visual
      pigment, and likewise expresses UVRh, BRh1 and LWRh mRNAs. Unexpectedly, in the
      female dorsal eye, we also found BRh1 co-expressed with LWRh in the R3-8
      photoreceptor cells. The ventral eye of both sexes, on the other hand, contains
      all four visual pigments and expresses all four opsin mRNAs in a non-overlapping
      fashion. Surprisingly, we found that the 500 nm visual pigment is encoded by a
      duplicate blue opsin gene, BRh2. Further, using molecular phylogenetic methods we
      trace this novel blue opsin gene to a duplication event at the base of the
      Polyommatine+Thecline+Lycaenine radiation. The blue opsin gene duplication may
      help explain the blueness of blue lycaenid butterflies.

PMID- 16888058
TI  - Sarcolemmal ion currents and sarcoplasmic reticulum Ca2+ content in ventricular
      myocytes from the cold stenothermic fish, the burbot (Lota lota).
AB  - The burbot (Lota lota) is a cold stenothermic fish species whose heart is adapted
      to function in the cold. In this study we use whole-cell voltage-clamp techniques
      to characterize the electrophysiological properties of burbot ventricular
      myocytes and to test the hypothesis that changes in membrane currents and
      intracellular Ca2+ cycling associated cold-acclimation in other fish species are
      routine for stenothermic cold-adapted species. Experiments were performed at 4
      degrees C, which is the body temperature of burbot for most of the year, and
      after myocytes were acutely warmed to 11 degrees C, which is in the upper range
      of temperatures experienced by burbot in nature. Results on K+ channels support
      our hypothesis as the relative density of K-channel conductances in the burbot
      heart are similar to those found for cold-acclimated cold-active fish species.
      I(K1) conductance was small (39.2+/-5.4 pS pF(-1) at 4 degrees C and 71.4+/-1.7
      pS pF(-1) at 11 degrees C) and I(Kr) was large (199+/-27 pS pF(-1) at 4 degrees C
      and 320.3+/-8 pS pF(-1) at 11 degrees C) in burbot ventricular myocytes. We found
      high Na+-Ca2+ exchange (NCX) activity (35.9+/-6.3 pS pF(-1) at 4 degrees C and
      58.6+/-8.4 pS pF(-1) at 11 degrees C between -40 and 20 mV), suggesting that it
      may be the primary pathway for sarcolemmal (SL) Ca2+ influx in this species. In
      contrast, the density (I(Ca), 0.81+/-0.13 pA pF(-1) at 4 degrees C, and 1.35+/
      0.18 pA pF(-1) at 11 degrees C) and the charge (Q(Ca), 0.24+/-0.043 pC pF(-1) at
      4 degrees C and 0.21+/-0.034 pC pF(-1) at 11 degrees C) carried by the L-type
      Ca2+ current was small. Our results on sarcolemmal ion currents in burbot
      ventricular myocytes suggest that cold stenothermy and compensative cold
      acclimation involve many of the same subcellular adaptations that culminate in
      enhanced excitability in the cold.

PMID- 16888059
TI  - Signalling pathways involved in hypertonicity- and acidification-induced
      activation of Na+/H+ exchange in trout hepatocytes.
AB  - In trout hepatocytes, hypertonicity and cytosolic acidification are known to
      stimulate Na+/H+ exchanger (NHE) activity, which contributes to recovery of cell
      volume and intracellular pH (pHi), respectively. The present study investigated
      the signalling mechanisms underlying NHE activation under these conditions.
      Exposing trout hepatocytes to cariporide, a specific inhibitor of NHE-1,
      decreased baseline pHi, completely blocked the hypertonicity-induced increase of
      pHi and reduced the hypertonicity-induced proton secretion by 80%. Changing
      extracellular pH (pHe) above and below normal values, and allowing cells to
      adjust pHi accordingly, significantly delayed alkalinization during hypertonic
      exposure, whereas following an acid load an enhanced pHi recovery with increasing
      pHe was seen. Chelating Ca2+, and thereby preventing the hypertonicity-induced
      increase in intracellular Ca2+ ([Ca2+]i), significantly diminished hypertonic
      elevation of pHi, indicating that Ca2+ signalling might be involved in NHE
      activation. A reduction in alkalinization and proton secretion was also observed
      in the presence of the protein kinase A (PKA) inhibitor H-89 or the calmodulin
      (CaM) inhibitor calmidazolium. A complete inhibition of hypertonic- and
      acidification-induced changes of pHi concurrent with an increase in
      hypertonically induced proton efflux was seen with the protein kinase C (PKC)
      inhibitor chelerythrine. Recovery of pHi following sodium propionate addition was
      reduced by more than 60% in the presence of cariporide, was sensitive to PKA
      inhibition, and tended to be reduced by CaM inhibition. In conclusion, we showed
      that NHE-1 is the main acid secretion mechanism during hypertonicity and recovery
      following acid loading. In addition, Ca2+-, PKA- and CaM-dependent pathways are
      involved in NHE-1 activation for recovery of cell volume and pHi. On the other
      hand, PKC appeared to have an impact on NHE-independent pathways affecting
      intracellular acid-base homeostasis.

PMID- 16888060
TI  - Flight control in the hawkmoth Manduca sexta: the inverse problem of hovering.
AB  - The inverse problem of hovering flight, that is, the range of wing movements
      appropriate for sustained flight at a fixed position and orientation, was
      examined by developing a simulation of the hawkmoth Manduca sexta. Inverse
      problems arise when one is seeking the parameters that are required to achieve a
      specified model outcome. In contrast, forward problems explore the outcomes given
      a specified set of input parameters. The simulation was coupled to a microgenetic
      algorithm that found specific sequences of wing and body motions, encoded by ten
      independent kinematic parameters, capable of generating the fixed body position
      and orientation characteristic of hovering flight. Additionally, we explored the
      consequences of restricting the number of free kinematic parameters and used this
      information to assess the importance to flight control of individual parameters
      and various combinations of them. Output from the simulated moth was compared to
      kinematic recordings of hovering flight in real hawkmoths; the real and simulated
      moths performed similarly with respect to their range of variation in position
      and orientation. The simulated moth also used average wingbeat kinematics
      (amplitude, stroke plane orientation, etc) similar to those of the real moths.
      However, many different subsets of the available kinematic were sufficient for
      hovering flight and available kinematic data from real moths does not include
      sufficient detail to assess which, if any, of these was consistent with the real
      moth. This general result, the multiplicity of possible hovering kinematics,
      shows that the means by which Manduca sexta actually maintains position and
      orientation may have considerable freedom and therefore may be influenced by many
      other factors beyond the physical and aerodynamic requirements of hovering
      flight.

PMID- 16888061
TI  - Unraveling the mechanical properties of composite silk threads spun by cribellate
      orb-weaving spiders.
AB  - Orb-web weaving spiders depend upon the mechanical performance of capture threads
      to absorb the energy of flying prey. Most orb-weavers spin wet capture threads
      with core fibers of flagelliform silk. These threads are extremely compliant and
      extensible due to the folding of their constituent proteins into molecular
      nanosprings and hydration by a surrounding coating of aqueous glue. In contrast,
      other orb-weavers use cribellate capture threads, which are composite structures
      consisting of core fibers of pseudoflagelliform silk surrounded by a matrix of
      fine dry cribellar fibrils. Based on phylogenetic evidence, cribellate capture
      threads predate the use of viscid capture threads. To better characterize how
      pseudoflagelliform and cribellar fibrils function, we investigated the mechanical
      performance of cribellate capture threads for three genera of spiders (Deinopis,
      Hyptiotes and Uloborus). These taxa spin very diverse web architectures, ranging
      from complete orbs to evolutionarily reduced triangle webs and cast nets. We
      found that the pseudoflagelliform core fibers of these webs were stiffer and
      stronger, but also less extensible, than flagelliform silk. However, cribellate
      capture threads achieved overall high extensibilities because the surrounding
      cribellar fibrils contributed substantially to the tensile performance of threads
      long after the core pseudoflagelliform fibers ruptured. In the case of Deinopis
      capture threads, up to 90% of the total work performed could be attributed to
      these fibrils. These findings yield insight into the evolutionary transition from
      cribellate to viscid capture threads.

PMID- 16888062
TI  - Acclimation to different thermal conditions in a northerly wintering shorebird is
      driven by body mass-related changes in organ size.
AB  - Seasonal acclimatization and experimental acclimation to cold in birds typically
      results from increased shivering endurance and elevated thermogenic capacity
      leading to improved resistance to cold. A wide array of physiological
      adjustments, ranging from biochemical transformations to organ mass variations,
      are involved in this process. Several studies have shown that improved cold
      endurance is accompanied by increases in summit metabolic rate (M(sum)), a
      measure of maximal heat production and an indicator of the level of sustainable
      thermogenic capacity. However, improved endurance to cold can also be achieved
      without significant changes in M(sum). The same is true for basal metabolic rate
      (BMR), which is known to increase in association with cold acclimatization or
      acclimation in some species but not in others. We investigated cold acclimation
      in a migrant shorebird known for extreme physiological flexibility, the red knot
      (Calidris canutus, the northerly wintering subspecies islandica). We measured BMR
      and M(sum) over two months in birds caught in the wild and transferred to
      experimentally controlled conditions representative of aspects of their seasonal
      thermal environment (two groups at constant 25 degrees C, one group at constant 4
      degrees C and two groups experiencing variable outdoor temperatures). Birds
      maintained in both cold and variable ambient temperatures showed a 14-15% higher
      body mass, 33-45% higher food intake, and 26% and 13% elevations in BMR and
      M(sum), respectively, compared with birds kept at thermoneutrality. These
      results, together with data on alimentary tract size and pectoral muscle
      thickness measured by ultrasonography, suggest that red knots acclimate to cold
      primarily through modulation of (lean) body mass components. Heavier individuals
      have larger muscles, which allow higher maximal heat production and better
      thermal compensation. Cold acclimation effects on BMR are most probably due to
      changes in the size of visceral organs, although not the alimentary tract in this
      specific case. The liver, known for its thermogenic capacity, is a probable
      candidate. Overall, our results indicate that relatively small changes in body
      mass and muscle size allow enough reserve capacity in terms of heat production to
      cope with typical wintering ambient temperature variations as measured on the red
      knot's wintering grounds.

PMID- 16888063
TI  - Age determination in individual wild-caught Drosophila serrata using pteridine
      concentration.
AB  - Fluorescence spectrophotometry can reliably detect levels of the pteridine 6
      biopterin in the heads of individual Drosophila serrata Malloch 1927. Pteridine
      content in both laboratory and field captured flies is typically a level of
      magnitude higher than the minimally detectable level (mean(lab)=0.54 units,
      mean(field)=0.44 units, minimum detectable level=0.01 units) and can be used to
      predict individual age in laboratory populations with high certainty (r2=57%).
      Laboratory studies of individuals of known age (from 1 to 48 days old) indicate
      that while pteridine level increases linearly with age, they also increase in a
      linear manner with rearing temperature and ambient light levels, but are
      independent of sex. As expected, the longevity of laboratory-reared males (at
      least 48 days) is higher than the range of predicted ages of wild-caught males
      based on individual pteridine levels (40 days). However, the predictive equation
      based on pteridine level alone suggested that a number of wild-caught males were
      less than 0 days old, and the 95% confidence limits for these predictions based
      on the inverse regression are broad. The age of the oldest wild-caught male is
      predicted to fall within the range of 2 to 50 days. The significant effects of
      temperature and light intensity determined in the laboratory study (effect sizes
      omega2=14.3 and 20.4%, respectively) suggests that the calibration of the age
      prediction equation for field populations would be significantly improved when
      combined with fine-scaled studies of habitat temperature and light conditions.
      The ability to determine relative age in individual wild-caught D. serrata
      presents great opportunities for a variety of evolutionary studies on the
      dynamics of natural populations.

PMID- 16888064
TI  - The energetic consequences of dietary specialization in populations of the garter
      snake, Thamnophis elegans.
AB  - We investigated the intraspecific variation in digestive energetics between
      dietary specialist and generalist populations of the Western Terrestrial garter
      snake (Thamnophis elegans) in northern California. Coastal populations have a
      specialized diet of slugs and inland populations have a generalized diet of fish,
      anurans, mice and leeches. The difference in prey preference between the two
      populations is congenital, heritable and ontogenetically stable. To examine
      energetic specializations and trade-offs in these populations, we measured the
      net assimilation efficiency of each snake population on both slug (Ariolimax
      columbianus) and fish (Rhinichthys osculus) diets. The net assimilation
      efficiency was measured during digestion of a meal and continued until metabolic
      rate re-attained prefeeding levels. Coastal snakes were able to utilize 62% more
      of the ingested energy towards production from slug diets through both increased
      assimilation of nutrients and reduced digestive costs. For fish, assimilation and
      digestive costs were the same in both coastal and inland populations. These
      results support the hypothesis that snakes with specialized diets can evolve
      physiological traits to extract nutrients more efficiently. However, there was no
      apparent trade-off on the more generalized diet that was associated with this
      specialization.

PMID- 16888065
TI  - Visual stimulation of saccades in magnetically tethered Drosophila.
AB  - Flying fruit flies, Drosophila melanogaster, perform ;body saccades', in which
      they change heading by about 90 degrees in roughly 70 ms. In free flight, visual
      expansion can evoke saccades, and saccade-like turns are triggered by similar
      stimuli in tethered flies. However, because the fictive turns in rigidly tethered
      flies follow a much longer time course, the extent to which these two behaviors
      share a common neural basis is unknown. A key difference between tethered and
      free flight conditions is the presence of additional sensory cues in the latter,
      which might serve to modify the time course of the saccade motor program. To
      study the role of sensory feedback in saccades, we have developed a new
      preparation in which a fly is tethered to a fine steel pin that is aligned within
      a vertically oriented magnetic field, allowing it to rotate freely around its yaw
      axis. In this experimental paradigm, flies perform rapid turns averaging 35
      degrees in 80 ms, similar to the kinematics of free flight saccades. Our results
      indicate that tethered and free flight saccades share a common neural basis, but
      that the lack of appropriate feedback signals distorts the behavior performed by
      rigidly fixed flies. Using our new paradigm, we also investigated the features of
      visual stimuli that elicit saccades. Our data suggest that saccades are triggered
      when expanding objects reach a critical threshold size, but that their timing
      depends little on the precise time course of expansion. These results are
      consistent with expansion detection circuits studied in other insects, but do not
      exclude other models based on the integration of local movement detectors.

PMID- 16888066
TI  - Molecular characterization of the first aromatic nutrient transporter from the
      sodium neurotransmitter symporter family.
AB  - Nutrient amino acid transporters (NATs, subfamily of sodium neurotransmitter
      symporter family SNF, a.k.a. SLC6) represent a set of phylogenetically and
      functionally related transport proteins, which perform intracellular absorption
      of neutral, predominantly essential amino acids. Functions of NATs appear to be
      critical for the development and survival in organisms. However, mechanisms of
      specific and synergetic action of various NAT members in the amino acid transport
      network are virtually unexplored. A new transporter, agNAT8, was cloned from the
      malaria vector mosquito Anopheles gambiae (SS). Upon heterologous expression in
      Xenopus oocytes it performs high-capacity, sodium-coupled (2:1) uptake of
      nutrients with a strong preference for aromatic catechol-branched substrates,
      especially phenylalanine and its derivatives tyrosine and L-DOPA, but not
      catecholamines. It represents a previously unknown SNF phenotype, and also
      appears to be the first sodium-dependent B(0) type transporter with a narrow
      selectivity for essential precursors of catecholamine synthesis pathways. It is
      strongly and specifically transcribed in absorptive and secretory parts of the
      larval alimentary canal and specific populations of central and peripheral
      neurons of visual-, chemo- and mechano-sensory afferents. We have identified a
      new SNF transporter with previously unknown phenotype and showed its important
      role in the accumulation and redistribution of aromatic substrates. Our results
      strongly suggest that agNAT8 is an important, if not the major, provider of an
      essential catechol group in the synthesis of catecholamines for neurochemical
      signaling as well as ecdysozoan melanization and sclerotization pathways, which
      may include cuticle hardening/coloring, wound curing, oogenesis, immune responses
      and melanization of pathogens.

PMID- 16888067
TI  - Molecular and cellular characterization of a new aquaporin, AQP-x5, specifically
      expressed in the small granular glands of Xenopus skin.
AB  - A new toad aquaporin (AQP) cDNA was cloned from a cDNA library constructed from
      the ventral skin of Xenopus laevis. This AQP (Xenopus AQP-x5) consisted of 273
      amino acid residues with a high sequence homology to mammalian AQP5. The
      predicted amino acid sequence contained the two conserved Asn-Pro-Ala motifs
      found in all major intrinsic protein (MIP) family members and six putative
      transmembrane domains. The sequence also contained a mercurial-sensitive cysteine
      and a putative phosphorylation motif site for protein kinase A at Ser-257. The
      swelling assay using Xenopus oocytes revealed that AQP-x5 facilitated water
      permeability. Expression of AQP-x5 mRNA was restricted to the skin, brain, lungs
      and testes. Immunofluorescence and immunoelectron microscopical studies using an
      anti-peptide antibody (ST-156) against the C-terminal region of the AQP-x5
      protein revealed the presence of immunopositive cells in the skin, with the label
      predominately localized in the apical plasma membrane of the secretory cells of
      the small granular glands. These glands are unique both in being close to the
      epidermal layer of the skin and in containing mitochondria-rich cells with
      vacuolar H+-ATPase dispersed among its secretory cells. Results from
      immunohistochemical experiments on the mucous or seromucous glands of several
      other anurans verified this result. We conclude that the presence of AQP-x5 in
      the apical plasma membrane of the small granular glands suggests its involvement
      in water secretion from the skins. The physiological roles of the AQP-x5 protein
      in the small or mucous glands are discussed.

PMID- 16888070
TI  - Exploring with damaged antennae: do crayfish compensate for injuries?
AB  - Appendages are important sources of sensory information for all animals that
      possess them but they are commonly damaged in nature. We describe how the tactile
      system of the crayfish Cherax destructor functioned when subjected to the kind of
      damage found in wild-caught or cultured animals. Touch information was
      methodically varied by the removal of antennae and chelae. The resulting
      behaviour was analysed in a T-maze. Crayfish with a single antenna ablated turned
      toward the intact appendage, however, those with only a partial ablation did not,
      suggesting that a tactile information threshold exists for normal behaviour. When
      exposed to the same environment after an antennal ablation but with no prior
      experience in that terrain, crayfish also turned toward the side of the intact
      antenna. By contrast, when animals with experience obtained in a previous trial
      with intact antennae were tested after ablation of one antenna, they did not turn
      into one arm of the maze more than the other. These two outcomes indicate that
      behaviour is affected by an interaction between the time at which an injury
      occurs and an animal's knowledge of the topography, and that an injury may affect
      learning. We also tested to see if other appendages could provide tactile
      information to compensate for antennal loss. Input from the chelae did not affect
      the turning behaviour of crayfish in the maze.

PMID- 16888068
TI  - Decreased expression of myogenic transcription factors and myosin heavy chains in
      Caenorhabditis elegans muscles developed during spaceflight.
AB  - The molecular mechanisms underlying muscle atrophy during spaceflight are not
      well understood. We have analyzed the effects of a 10-day spaceflight on
      Caenorhabditis elegans muscle development. DNA microarray, real-time quantitative
      PCR, and quantitative western blot analyses revealed that the amount of MHC in
      both body-wall and pharyngeal muscle decrease in response to spaceflight.
      Decreased transcription of the body-wall myogenic transcription factor HLH-1
      (CeMyoD) and of the three pharyngeal myogenic transcription factors, PEB-1, CEH
      22 and PHA-4 were also observed. Upon return to Earth animals displayed reduced
      rates of movement, indicating a functional defect. These results demonstrate that
      C. elegans muscle development is altered in response to spaceflight. This altered
      development occurs at the level of gene transcription and was observed in the
      presence of innervation, not simply in isolated cells. This important finding
      coupled with past observations of decreased levels of the same myogenic
      transcription factions in vertebrates after spaceflight raises the possibility
      that altered muscle development is a contributing factor to spaceflight-induced
      muscle atrophy in vertebrates.

PMID- 16888069
TI  - Critical role of zinc in hardening of Nereis jaws.
AB  - Hardening of invertebrate jaws and mandibles has been previously correlated to
      diverse, potentially complex modifications. Here we demonstrate directly, for the
      first time, that Zn plays a critical role in the mechanical properties of
      histidine-rich Nereis jaws. Using nanoindentation, we show that removal of Zn by
      chelation decreases both hardness and modulus by over 65%. Moreover,
      reconstitution of Zn yields a substantial recovery of initial properties. Modulus
      and hardness of Zn-replete jaws exceed those attainable by current engineering
      polymers by a factor of >3. Zn-mediated histidine cross-links are proposed to
      account for this enhancement in mechanical properties.

PMID- 16888071
TI  - Hydrogen sulfide mediates hypoxia-induced relaxation of trout urinary bladder
      smooth muscle.
AB  - Hydrogen sulfide (H2S) is a recently identified gasotransmitter that may mediate
      hypoxic responses in vascular smooth muscle. H2S also appears to be a signaling
      molecule in mammalian non-vascular smooth muscle, but its existence and function
      in non-mammalian non-vascular smooth muscle have not been examined. In the
      present study we examined H2S production and its physiological effects in urinary
      bladder from steelhead and rainbow trout (Oncorhynchus mykiss) and evaluated the
      relationship between H2S and hypoxia. H2S was produced by trout bladders, and its
      production was sensitive to inhibitors of cystathionine beta-synthase and
      cystathionine gamma-lyase. H2S produced a dose-dependent relaxation in
      unstimulated and carbachol pre-contracted bladders and inhibited spontaneous
      contractions. Bladders pre-contracted with 80 mmol l(-1) KCl were less sensitive
      to H2S than bladders contracted with either 80 mmol l(-1) KC2H3O2 (KAc) or
      carbachol, suggesting that some of the H2S effects are mediated through an ion
      channel. However, H2S relaxation of bladders was not affected by the potassium
      channel inhibitors, apamin, charybdotoxin, 4-aminopyridine, and glybenclamide, or
      by chloride channel/exchange inhibitors 4,4'-Diisothiocyanatostilbene-2,2'
      disulfonic acid disodium salt, tamoxifen and glybenclamide, or by the presence or
      absence of extracellular HCO3-. Inhibitors of neuronal mechanisms, tetrodotoxin,
      strychnine and N-vanillylnonanamide were likewise ineffective. Hypoxia (aeration
      with N2) also relaxed bladders, was competitive with H2S for relaxation, and it
      was equally sensitive to KCl, and unaffected by neuronal blockade or the presence
      of extracellular HCO3-. Inhibitors of H2S synthesis also inhibited hypoxic
      relaxation. These experiments suggest that H2S is a phylogenetically ancient
      gasotransmitter in non-mammalian non-vascular smooth muscle and that it serves as
      an oxygen sensor/transducer, mediating the effects of hypoxia.

PMID- 16888072
TI  - Members of the crustacean hyperglycemic hormone (CHH) peptide family are
      differentially distributed both between and within the neuroendocrine organs of
      Cancer crabs: implications for differential release and pleiotropic function.
AB  - The crustacean hyperglycemic hormone (CHH) family of peptides includes CHH, moult
      inhibiting hormone (MIH) and mandibular organ-inhibiting hormone (MOIH). In the
      crab Cancer pagurus, isoforms of these peptides, as well as CHH precursor-related
      peptide (CPRP), have been identified in the X-organ-sinus gland (XO-SG) system.
      Using peptides isolated from the C. pagurus SG, antibodies to each family member
      and CPRP were generated. These sera were then used to map the distributions and
      co-localization patterns of these peptides in the neuroendocrine organs of seven
      Cancer species: Cancer antennarius, Cancer anthonyi, Cancer borealis, Cancer
      gracilis, Cancer irroratus, Cancer magister and Cancer productus. In addition to
      the XO-SG, the pericardial organ (PO) and two other neuroendocrine sites
      contained within the stomatogastric nervous system, the anterior cardiac plexus
      (ACP) and the anterior commissural organ (ACO), were studied. In all species, the
      peptides were found to be differentially distributed between the neuroendocrine
      sites in conserved patterns: i.e. CHH, CPRP, MIH and MOIH in the XO-SG, CHH, CPRP
      and MOIH in the PO, and MOIH in the ACP (no immunolabeling was found in the ACO).
      Moreover, in C. productus (and probably in all species), the peptides present in
      the XO-SG and PO were differentially distributed between the neurons within each
      of these neuroendocrine organs (e.g. CHH and CPRP in one set of XO somata with
      MIH and MOIH co-localized in a different set of cell bodies). Taken collectively,
      the differential distributions of CHH family members and CPRP both between and
      within the neuroendocrine organs of crabs of the genus Cancer suggests that each
      of these peptides may be released into the circulatory system in response to
      varied, tissue-specific cues and that the PO- and/or ACP-derived isoforms may
      possess functions distinct from those classically ascribed to their release from
      the SG.

PMID- 16888073
TI  - Regulation of osmotic stress transcription factor 1 (Ostf1) in tilapia
      (Oreochromis mossambicus) gill epithelium during salinity stress.
AB  - Mechanisms of induction of osmotic stress transcription factor 1 (Ostf1) were
      analyzed in gill epithelium of tilapia exposed to salinity stress. Experiments
      with primary cultures of gill epithelial cells revealed that hyperosmotic Ostf1
      induction was independent of systemic factors. In addition, the synthetic
      glucocorticoid receptor agonist dexamethasone did not affect Ostf1 levels,
      arguing against cortisol being the signal for Ostf1 induction during hyperosmotic
      stress. Exposure of primary gill cell cultures to a hyperosmotic agent that is
      cell permeable and non-hypertonic (glycerol) did not trigger Ostf1 induction.
      However, when gill cells were exposed to hypertonicity (either in the form of
      NaCl or other forms) Ostf1 was rapidly and significantly induced. Analysis of
      hnRNA and mRNA levels revealed that Ostf1 upregulation in gill cells of intact
      fish and primary cultures of gill epithelial cells was mediated by transient mRNA
      stabilization. In addition to the initial transient mRNA stabilization a
      subsequent transcriptional induction of Ostf1 was observed. In cultured gill
      cells increase in Ostf1 mRNA synthesis was stable and very potent, whereas in
      gill cells of intact fish this increase was transient. This observation suggests
      positive feedback by Ostf1 or one of its targets and negative feedback by
      systemic factors on Ostf1 transcription. We conclude that Ostf1 induction in gill
      epithelial cells of tilapia exposed to salinity stress (1) is independent of
      cortisol or other systemic factors; (2) depends on hypertonicity as the signal;
      and (3) is based on transient mRNA stabilization. Moreover, our data on primary
      cell cultures show that systemic signals are necessary to prevent sustained
      transcriptional induction of Ostf1 during hyperosmotic stress, indicating
      feedback regulation and a high degree of complexity of osmosensing and signaling
      networks in euryhaline fishes.

PMID- 16888074
TI  - What can bees really tell us about the face processing system in humans?

PMID- 16888075
TI  - Haplotypes, mutations and male fertility: the story of the testis-specific
      ubiquitin protease USP26.
AB  - Recently, mutations in the X-linked ubiquitin protease 26 (USP26) gene have been
      proposed to be associated with male infertility. In particular a 371insACA,
      494T>C and 1423C>T haplotype, which results in a T123-124ins, L165S and H475Y
      amino acid change respectively, has been reported to be associated with Sertoli
      cell-only syndrome (SCOS) and an absence of sperm in the ejaculate. Here, we
      demonstrate that two of these changes actually correspond to the ancestral
      sequence of the gene and that the USP26 haplotype is present in significant
      frequencies in sub-Saharan African and South and East Asian populations,
      including in individuals with known fertility. This indicates that the allele is
      not associated with infertility. The pattern of frequency distribution of the
      derived haplotype (371delACA, 494T), which is present at high frequencies in most
      non-African populations could be interpreted as either a result of migration
      followed by simple genetic drift or alternatively as positive selection acting on
      the derived alleles. The latter hypothesis seems likely, because there is
      evidence of strong positive selection acting on the USP26 gene.

PMID- 16888076
TI  - PGE2 up-regulates EGF-like growth factor biosynthesis in human granulosa cells:
      new insights into the coordination between PGE2 and LH in ovulation.
AB  - LH and prostaglandin E(2) (PGE(2)) share many similar effects on the pre
      ovulatory follicle. They can induce independently cumulus expansion, the
      resumption of meiosis and progesterone production. However, cyclooxygenase-2 (COX
      2) inhibitors were found to hinder most of the LH-induced effects. Recently, EGF
      like growth factors amphiregulin (Ar) and epiregulin (Ep) were found to be
      produced in response to LH stimulation and to induce cumulus expansion and oocyte
      maturation. We aimed at evaluating whether PGE(2) induces Ar and Ep syntheses in
      human granulosa cells and whether the inhibition of PGE(2) production by
      selective COX-2 inhibitor, nimesulide, affects LH-induced Ar and Ep biosynthesis.
      Ar and Ep mRNA levels increased following PGE(2) stimulation, in a dose- and time
      dependent manner, which resembled those of LH. The blockade of protein kinase A
      (PKA) (by H89) and mitogen-activated protein kinase (MAPK) (by UO126) reduced the
      expression of PGE(2)-induced Ar and Ep biosynthesis. Although the stimulation of
      the cells with LH in the presence of nimesulide did not change the progesterone
      levels, it resulted in a significant reduction of Ar and Ep biosynthesis. In
      conclusion, PGE(2) may mimic LH action, at least in part, by the induction of Ar
      and Ep biosynthesis, which involves cAMP/PKA and MAPK pathways. The negative
      effect of nimesulide on the ovulatory process may be due to the reduction of Ar
      and Ep biosynthesis, which implies a possible collaborative role between PGE(2)
      and LH on their induction.

PMID- 16888077
TI  - Interleukin-1-induced NF-kappaB recruitment to the oxytocin receptor gene
      inhibits RNA polymerase II-promoter interactions in cultured human myometrial
      cells.
AB  - The myometrial oxytocin receptor (OTR) is highly regulated during pregnancy,
      reaching maximal concentrations near term. These levels are then abruptly reduced
      in advanced labour and the post-partum period. Our goal was to examine the
      molecular basis for this reduction, using chromatin immunoprecipitation (ChIP).
      Interleukin-1alpha (IL1A) treatment of cultured human myometrial cells has
      previously been shown to reduce steady-state levels of OTR mRNA. We show further
      that IL1A reduced RNA polymerase II cross-linking to the otr promoter, as
      reflective of transcriptional inhibition. IL1A also increased the recruitment of
      nuclear factor kappaB (NF-kappaB) to a site 955 bp upstream from the
      transcriptional start site. Inhibition of NF-kappaB activation negated the
      effects of IL1A on polymerase II dissociation, indicating a causal relationship,
      at least in part, between recruitment of NF-kappaB and detachment of polymerase
      from the otherwise constitutively active otr promoter. IL1A treatment also
      resulted in increased histone H4 acetylation in the otr promoter region. Whereas
      NF-kappaB recruitment and histone acetylation are generally associated with
      activation of gene expression, our findings show that both processes can be
      involved in dissociation of RNA polymerase II from an active promoter. The
      results of these studies suggest that the elevation of IL1 in the myometrium
      occurring at the end of pregnancy initiates the process of down-regulation of
      OTRs in advanced labour, resulting in the desensitization of the myometrium to
      elevated levels of OT in the blood during lactation.

PMID- 16888078
TI  - Flow cytometric analysis of micronuclei in peripheral blood reticulocytes: I.
      Intra- and interlaboratory comparison with microscopic scoring.
AB  - Accumulating evidence suggests that reticulocytes (RETs) in the peripheral blood
      of rats may represent a suitable cell population for use in the micronucleus
      assay, despite the ability of the rat spleen to selectively remove micronucleated
      erythrocytes from the peripheral circulation. To evaluate the analytical
      performance of a previously described flow cytometric method (Torous et al.,
      2003, Toxicol. Sci. 74, 309-314) that may allow this assay to be conducted using
      peripheral blood in lieu of bone marrow sampling, we compared the sensitivity and
      performance characteristics of the flow cytometric technique with two established
      microscopy-based scoring methods. Peripheral blood samples from single Sprague
      Dawley rats treated for 6 days with either vehicle or cyclophosphamide were
      prepared in replicate for scoring by the three methods at different laboratories.
      These blood-based measurements were compared to those derived from bone marrow
      specimens from the same animals, stained with acridine orange, and scored by
      microscopy. Through the analysis of replicate specimens, inter- and
      intralaboratory variability were evaluated for each method. Scoring
      reproducibility over time was also evaluated. These data support the premise that
      rat RETs harvested from peripheral blood are a suitable cell population to assess
      genotoxicant-induced micronucleus formation. The interlaboratory comparison
      provides evidence of the general robustness of the micronucleus endpoint using
      different analytical approaches. Furthermore, data presented herein demonstrate a
      clear advantage of flow cytometry-based scoring over microscopy-significantly
      lower inter- and intralaboratory variation and higher statistical sensitivity.

PMID- 16888079
TI  - Flow cytometric analysis of micronuclei in peripheral blood reticulocytes: II. An
      efficient method of monitoring chromosomal damage in the rat.
AB  - We have evaluated a flow cytometric method that allows assessment of
      micronucleated reticulocytes (MN-RETs) in microliter quantities of peripheral
      blood and compared results using this assay with those of established microscopic
      methods of scoring bone marrow and peripheral blood from rats treated with well
      characterized genotoxic agents. Young reticulocytes (RETs) are labeled with FITC
      anti-CD71 (transferrin receptor) and micronuclei with propidium iodide (with
      RNase treatment). Red blood cells parasitized with Plasmodia serve as a
      calibration standard for DNA content. Microscopic scoring used acridine orange
      (AO) staining of methanol-fixed slides or supravital AO staining. The effect of
      the rat spleen on the parameters evaluated was determined by comparing age- and
      sex-matched normal and splenectomized rats treated with cyclophosphamide, cis
      platin, or vinblastine under treatment conditions that established a steady-state
      frequency of MN-RETs in the bone marrow and peripheral blood compartments. The
      data demonstrate the sensitivity and reproducibility of the flow cytometric assay
      in the Sprague-Dawley rat, and comparative studies using identical blinded
      samples at multiple laboratories show that inter- and intra-laboratory
      reproducibility is much higher with the flow method than with the microscopic
      methods currently employed for regulatory studies. A significant effect of
      splenic selection against genotoxicant-induced MN-RETs was observed with each of
      the three scoring methodologies, despite the fact that the flow and supravital AO
      techniques restrict analysis to the youngest fraction of RETs. The high precision
      of flow-based measurements also demonstrated a slight but statistically
      significant level of selection against spontaneously arising MN-RET. Despite
      these spleen effects, assay sensitivity for blood-based analyses was maintained
      by the flow method as it was shown to have superior counting statistics, lower
      variability, and higher sensitivity than manual scoring. The data suggest that
      flow cytometric assessment of micronucleus induction can be integrated into
      routine toxicity testing, eliminating the need for a separate bioassay.

PMID- 16888080
TI  - Sequential high dose chemotherapy as initial treatment for aggressive sub-types
      of non-Hodgkin lymphoma: results of the international randomized phase III trial
      (MISTRAL).
AB  - INTRODUCTION: Sequential high dose (SHiDo) chemotherapy with stem cell support
      has been shown to prolong the event-free survival in patients with diffuse large
      B-cell lymphoma. METHODS: To confirm this result in a multicenter trial, we
      randomized patients with aggressive NHL, to receive either eight cycles of CHOP
      or SHiDo. The primary endpoint was overall survival. RESULTS: 129 evaluable
      patients were randomized to receive either CHOP or SHiDo: median age, 48 years;
      62% male; stage III+IV: 73%; age adjusted International Prognostic Index 1/2/3:
      21%/52%/27%. Toxicity grades 3+4 were more pronounced in the SHiDo-arm with 13%
      versus 3% of patients with fever; 34% versus 13% with infections; 13% versus 2%
      with esophagitis/dysphagia/gastric ulcer. The remission rates were similar in
      SHiDo and CHOP arms with 34%/37% complete remissions and 31%/31% partial
      remissions, respectively. After a median observation time of 48 months, there was
      no difference in overall survival at 3 years, with 46% for SHiDo and 53% for CHOP
      (P = 0.48). CONCLUSION: In this multicenter trial, early intensification with
      SHiDo did not confer any survival benefit in previously untreated patients with
      aggressive NHL and was associated with a higher incidence of grades 3/4 toxicity.

PMID- 16888081
TI  - Effect of transforming growth factor-beta receptor I kinase inhibitor 2,4
      disubstituted pteridine (SD-208) in chronic allergic airway inflammation and
      remodeling.
AB  - Transforming growth factor (TGF)-beta is a multifunctional regulator of cell
      growth and differentiation with both pro- and anti-inflammatory properties. We
      used an inhibitor of TGF-beta receptor I (TGF-betaRI) kinase, SD-208 (2,4
      disubstituted pteridine, a ATP-competitive inhibitor of TGF-betaRI kinase), to
      determine the role of TGF-beta in airway allergic inflammation and remodeling.
      Brown-Norway rats sensitized and repeatedly exposed to ovalbumin (OVA) aerosol
      challenge were orally administered SD-208 twice daily, before each of six OVA
      exposures to determine the preventive effects, or only before each of the last
      three of six OVA exposures to investigate its reversal effects. SD-208 (60 mg/kg)
      reversed bronchial hyperresponsiveness (BHR) induced by repeated allergen
      exposure, but it did not prevent it. SD-208 prevented changes in serum total and
      OVA-specific IgE, but it did not reverse them. SD-208 had both a preventive and
      reversal effect on airway inflammation as measured by major basic protein
      positive eosinophils and CD2(+) T-cell counts in mucosal airways, cell
      proliferation measured by 5-bromo-2'-deoxyuridine expression in airway smooth
      muscle (ASM) cells and epithelial cells, and goblet cell hyperplasia induced by
      repeated allergen challenges. There was a significant decrease in intracellular
      Smad2/3 expression. SD-208 did not significantly decrease the increased ASM
      thickness induced by allergen exposure. These findings support a proinflammatory
      and proremodeling role for TGF-beta in allergic airway inflammation. Inhibition
      of TGF-betaRI kinase activities by SD-208 may be a useful approach to the
      reversal of BHR and to the prevention and reversal of inflammatory and remodeling
      features of chronic asthma.

PMID- 16888082
TI  - Enhanced thromboxane receptor-mediated responses and impaired endothelium
      dependent relaxation in human corpus cavernosum from diabetic impotent men: role
      of protein kinase C activity.
AB  - We have evaluated the influence of protein kinase C (PKC) activity on penile
      smooth muscle tone in tissues from diabetic and nondiabetic men with erectile
      dysfunction. Human corpus cavernosum (HCC) strips were obtained from impotent
      diabetic and nondiabetic men at the time of penile prosthesis implantation and
      studied in organ chambers. Contractility responses to a prostanoid precursor, to
      prostanoids, and to the endothelium-dependent vasodilator acetylcholine were
      studied. Arachidonic acid (AA; 100 microM) caused cyclooxygenase-dependent
      relaxation of HCC. This relaxation was impaired in diabetic tissues and
      normalized by blocking thromboxane (TP) receptors with 20 nM [1S
      [1alpha,2alpha(Z),3alpha,4alpha]]-7-[3-[[2
      [(phenylamino)carbonyl]hydrazino]methyl]-7-oxabicyclo[2.2.1]hept-2-yl]-5
      heptenoic acid (SQ29548). Diabetes did not affect prostaglandin (PG)E(1)-induced
      relaxation, but it reduced relaxation induced by the PGE(1) metabolite PGE(0).
      This effect was related to an interaction of PGE(0) with TP receptors. Diabetic
      tissues had reduced endothelium-dependent relaxation, which was partially
      improved by SQ29548 and completely normalized by the PKC inhibitor 3-[1-[3
      (dimethylaminopropyl]-1H-indol-3-yl]-4-(1H-indol-3-yl)-1H-pyrrole-2,5-dione
      monohydrochloride (GF109203X; 1 microM). In HCC from nondiabetic patients,
      treatment with the PKC activator phorbol-12,13-dibutyrate (0.3 microM)
      significantly attenuated endothelium-dependent relaxation, an effect prevented by
      coadministration of GF109203X. Tissues from diabetic patients had enhanced
      sensitivity to the contractile effects of the TP receptor agonist 9,11-dideoxy
      9alpha,11alpha-epoxymethano PGF(2alpha) (U46619) (EC(50) = 0.65 +/- 0.42 and 6.01
      +/- 2.28 nM in diabetic and nondiabetic patients, respectively). Inhibition of
      PKC with 1 microM GF109203X, prevented diabetes-induced hypersensitivity to
      U46619-induced contractions (EC(50) = 8.55 +/- 3.12 microM). Overactivity of PKC
      in diabetes is responsible for enhanced contraction and reduced endothelium
      dependent relaxation of HCC smooth muscle. Such alterations can result in
      erectile dysfunction.

PMID- 16888083
TI  - Suppression of experimental colitis by intestinal mononuclear phagocytes.
AB  - The contribution of innate immunity to inflammatory bowel disease (IBD) remains
      an area of intense interest. Macrophages (MO) and dendritic cells (DC) are
      considered important factors in regulating the onset of IBD. The goal of this
      study was to determine if intestinal mononuclear phagocytes (iMNP) serve a
      pathological or protective role in dextran sulfate sodium (DSS)-induced colitis
      in mice. Using a conditional MO/DC depletion transgenic mouse line--MO Fas
      induced apoptosis--to systemically deplete iMNP, DSS colitis histopathology was
      shown to be more severe in MO/DC-depleted compared with MO/DC-intact mice.
      Similarly, localized iMNP depletion by clodronate-encapsulated liposomes into
      C57BL/6, BALB/c, and CB.17/SCID mice also increased DSS colitis severity, as
      indicated by increased histopathology, weight loss, rectal bleeding, decreased
      stool consistency, and colon length compared with MO/DC-intact, DSS-treated mice.
      Histology revealed that iMNP depletion during DSS treatment led to increased
      neutrophilic inflammation, increased epithelial injury, and enhanced mucin
      depletion from Goblet cells. iMNP depletion did not further elevate DSS-induced
      expression of TNF-alpha and IFN-gamma mRNA but significantly increased expression
      of CXCL1 chemokine mRNA. Myeloperoxidase activity was increased in colons of
      MO/DC-depleted, DSS-treated mice, compared with DSS alone, coincident with
      increased neutrophil infiltration in diseased colons. Neutrophil depletion
      combined with MO/DC depletion prevented the increase in DSS colitis severity
      compared with MO/DC depletion alone. This study demonstrates that iMNP can serve
      a protective role during development of acute colitis and that protection is
      associated with MO/DC-mediated down-regulation of neutrophil infiltration.

PMID- 16888084
TI  - A selective small molecule agonist of the melanocortin-1 receptor inhibits
      lipopolysaccharide-induced cytokine accumulation and leukocyte infiltration in
      mice.
AB  - It is well established that melanocortins are peptides that have potent anti
      inflammatory activity. Recent research has focused on understanding which of the
      known melanocortin receptors mediates the anti-inflammatory actions of the
      melanocortins. The aim of this study was to assess the anti-inflammatory activity
      of a synthetic MC-1R agonist. BMS-470539 is a potent, selective, full agonist of
      human and murine MC-1R with EC(50) values in a cAMP accumulation assay of 16.8
      and 11.6 nM, respectively. BMS-470539 dose-dependently inhibited TNF-alpha
      induced activation of a NF-kappaB transcriptional reporter in human melanoma
      cells, which endogenously express MC-1R. In vivo studies with BMS-470539
      demonstrated that subcutaneous administration of BMS-470539 resulted in a dose
      dependent inhibition of LPS-induced TNF-alpha production in BALB/c mice. In this
      model, the compound had an ED(50) of approximately 10 micromol/kg and a
      pharmacodynamic half-life of approximately 8 h. Pharmacokinetic analysis of the
      compound indicated that the compound had a t(1/2) of 1.7 h. In a model of lung
      inflammation, administration of 15 micromol/kg BMS-470539 resulted in a 45%
      reduction in LPS-induced leukocyte infiltration (an infiltrate comprised
      primarily of neutrophils). The compound was also effective in a model of delayed
      type hypersensitivity, reducing paw swelling by 59%, comparable with that seen
      with 5 mg/kg dexamethasone. These studies demonstrate that a selective small
      molecule agonist of the melanocortin-1 receptor is a potent anti-inflammatory
      agent in vivo and provides compelling evidence for the involvement of this
      receptor in the modulation of inflammation.

PMID- 16888086
TI  - The bone marrow constitutes a reservoir of pericyte progenitors.
AB  - Adult bone marrow is a rich reservoir of hematopoietic and mesenchymal stem and
      progenitor cells. Mobilization and recruitment of bone marrow-derived cells to
      injured or ischemic tissue or tumors endorse the initiation and maintenance of
      angiogenic processes in the adult by incorporating endothelial progenitor cells
      (EPC) into the developing vasculature and by recruiting accessory hematopoietic
      cells. Recent data have now revealed that the origin of bone marrow-derived
      vascular cells is not restricted to endothelial cells but also includes pericytes
      -the perivascular support cells. Several laboratories have now reported the
      existence of pericyte progenitor cells, and these cells, like EPC, can be
      mobilized and recruited to the remodeling vasculature under ischemic conditions
      and in tumors. This review focuses on pericytes in vessel formation and on recent
      discoveries about their bone marrow origin in the adult.

PMID- 16888085
TI  - Identification and characterization of a human monoclonal antagonistic antibody
      AL-57 that preferentially binds the high-affinity form of lymphocyte function
      associated antigen-1.
AB  - LFA-1 (alpha(L)beta(2)) mediates cell-cell and cell-extracellular matrix
      adhesions essential for immune and inflammatory responses. One critical mechanism
      regulating LFA-1 activity is the conformational change of the ligand-binding
      alpha(L) I domain from low-affinity (LA), closed form, to the high-affinity (HA),
      open form. Most known integrin antagonists bind both forms. Antagonists specific
      for the HA alpha(L) I domain have not been described. Here, we report the
      identification and characterization of a human antibody AL-57, which binds to the
      alpha(L) I domain in a HA but not LA conformation. AL-57 was discovered by
      selection from a human Fab-displaying library using a locked-open HA I domain as
      target. AL-57 Fab-phage bound HA I domain-expressing K562 cells (HA cells) in a
      Mg(2+)-dependent manner. AL-57 IgG also bound HA cells and PBMCs, activated by
      Mg(2+)/EGTA, PMA, or DTT. The binding profile of AL-57 IgG on PBMCs was the same
      as that of ICAM-1, the main ligand of LFA-1. In contrast, an anti-alpha(L) murine
      mAb MHM24 did not distinguish between the HA and LA forms. Moreover, AL-57 IgG
      blocked ICAM-1 binding to HA cells with a potency greater than MHM24. It also
      inhibited ICAM-1 binding to PBMCs, blocked adhesion of HA cells to keratinocytes,
      and inhibited PHA-induced lymphocyte proliferation with potencies comparable with
      MHM24. These results indicate that specifically targeting the HA I domain is
      sufficient to inhibit LFA-1-mediated, adhesive functions. AL-57 represents a
      therapeutic candidate for treatment of inflammatory and autoimmune diseases.

PMID- 16888088
TI  - Human CD4+ T lymphocytes with increased intracellular cAMP levels exert
      regulatory functions by releasing extracellular cAMP.
AB  - We have previously shown that cholera toxin (CT) and other cAMP-elevating agents
      induce up-regulation of the inhibitory molecule CTLA-4 on human resting T
      lymphocytes. In this study, we evaluated the function of these cells. We found
      that purified human CD4(+) T lymphocytes pretreated with CT were able to inhibit
      proliferation of autologous PBMC in a dose-dependent manner. It is interesting
      that this phenomenon was not mediated by inhibitory cytokines such as IL-10, IL
      4, or TGF-beta but was in part caused by the release of extracellular cAMP by the
      CD4(+) T lymphocytes. Purified CD4(+) T cells pretreated with forskolin, a
      transient cAMP inducer, or with dibutyryl cAMP, an analog of cAMP, did not exert
      suppressive functions, suggesting that a sustained production of cAMP, such as
      that induced by CT, was required to identify a novel regulatory function mediated
      by CD4(+) T cells. Our results show that CD4(+) T lymphocytes can exert
      regulatory functions through the release of extracellular cAMP and that the
      cyclic nucleotide acts as a primary messenger, which could play a biological role
      in the modulation of immune responses.

PMID- 16888087
TI  - Normal hematopoiesis after conditional targeting of RXRalpha in murine
      hematopoietic stem/progenitor cells.
AB  - Because of the retinoic acid receptor-alpha (RARalpha) gene's involvement in
      acute promyelocytic leukemia, the important role of RARs in hematopoiesis is now
      well established. However, relatively few studies of hematopoiesis have focused
      on the role of the retinoid X receptors (RXRs), the obligate heterodimeric
      partners of the RARs. We sought to establish whether conditional targeting of
      RXRalpha in early hematopoietic progenitors, ideally to the level of the
      hematopoietic stem cell (HSC), would compromise hematopoiesis. For hematopoietic
      targeting of RXRalpha, we characterized IFN-inducible MxCre mice for use in
      studying the role of RXRalpha in hematopoiesis. We established that MxCre
      executes recombination of loxP-flanked RXRalpha in hematopoietic progenitors
      immunophenotypically enriched for HSC, leading to widespread and sustained
      targeting of RXRalpha in hematopoietic cells. However, we found no evidence of
      hematologic compromise in mice lacking RXRalpha, suggesting that RXRalpha is
      dispensable for normal murine hematopoiesis. Nonetheless, RXRalpha null bone
      marrow cells cultured in methylcellulose form colonies more efficiently than bone
      marrow cells obtained from control mice. This result suggests that although
      RXRalpha is not required for murine hematopoiesis, there may be hematopoietic
      signaling pathways that respond selectively to RXRalpha or settings in which
      combined expression of RXR (alpha, beta, and gamma) is limiting.

PMID- 16888089
TI  - Acetylation of GATA-1 is required for chromatin occupancy.
AB  - All 3 hematopoietic GATA transcription factors, GATA-1, GATA-2, and GATA-3, are
      acetylated, although the in vivo role of this modification remains unclear. We
      examined the functions of an acetylation-defective mutant of GATA-1 in maturing
      erythroid cells. We found that removal of the acetylation sites in GATA-1 does
      not impair its nuclear localization, steady-state protein levels, or its ability
      to bind naked GATA elements in vitro. However, chromatin immunoprecipitation
      (ChIP) experiments revealed that mutant GATA-1 was dramatically impaired in
      binding to all examined cellular target sites in vivo, including genes that are
      normally activated and repressed by GATA-1. Together, these results suggest that
      acetylation regulates chromatin occupancy of GATA-1. These findings point to a
      novel function for transcription factor acetylation, perhaps by facilitating
      protein interactions required for stable association with chromatin templates in
      vivo.

PMID- 16888090
TI  - CXCR4 is a prognostic marker in acute myelogenous leukemia.
AB  - CXCR4 chemokine receptors retain hematopoietic progenitors and leukemia cells
      within the marrow microenvironment. We prospectively evaluated the prognostic
      implication of CXCR4 in 90 consecutive patients with acute myelogenous leukemia
      (AML) by flow cytometry. Patients were divided into groups with low (n=32),
      intermediate (n=26), or high (n=32) CXCR4 expression, as defined by CXCR4 mean
      fluorescence intensity ratio thresholds of less than 5, 5 to 10, or more than 10,
      respectively. We found that low CXCR4 expression on AML cells correlated with a
      better prognosis, resulting in a longer relapse-free and overall survival of
      24.3+/-2.9 months for low CXCR4-expressing patients, compared with 17.4+/-3.4
      months for intermediate and 12.8+/-2 months (mean+/-SEM) for patients with high
      expression. In univariate analyses, CXCR4 expression, cytogenetics, white blood
      cell count, and serum lactate dehydrogenase (LDH) predicted for shorter survival.
      Multivariate analysis revealed CXCR4 expression and unfavorable cytogenetics as
      independent prognostic factors. We conclude that CXCR4 expression in AML is an
      independent prognostic predictor for disease relapse and survival that can
      rapidly and easily be determined at disease presentation. These findings warrant
      further investigation into the role of CXCR4 in AML and suggest that CXCR4 should
      be incorporated into the risk assessment of AML patients.

PMID- 16888091
TI  - Negative regulation of primitive hematopoiesis by the FGF signaling pathway.
AB  - Hematopoiesis is controlled by multiple signaling molecules during embryonic and
      postnatal development. The function of the fibroblast growth factor (FGF) pathway
      in this process is unclear. Here we show that FGF plays a key role in the
      regulation of primitive hematopoiesis in chicks. Using hemoglobin mRNA expression
      as a sensitive marker, we demonstrate that timing of blood differentiation can be
      separated from that of initial mesoderm patterning and subsequent migration. High
      FGF activity inhibits primitive blood differentiation and promotes endothelial
      cell fate. Conversely, inhibition of FGFR activity leads to ectopic blood
      formation and down-regulation of endothelial markers. Expression and functional
      analyses indicate that FGFR2 is the key receptor mediating these effects. The FGF
      pathway regulates primitive hematopoiesis by modulating Gata1 expression level
      and activity. We propose that the FGF pathway mediates repression of globin gene
      expression and that its removal is essential before terminal differentiation can
      occur.

PMID- 16888092
TI  - AML1/Runx1 rescues Notch1-null mutation-induced deficiency of para-aortic
      splanchnopleural hematopoiesis.
AB  - The Notch1-RBP-Jkappa and the transcription factor Runx1 pathways have been
      independently shown to be indispensable for the establishment of definitive
      hematopoiesis. Importantly, expression of Runx1 is down-regulated in the para
      aortic splanchnopleural (P-Sp) region of Notch1- and Rbpsuh-null mice. Here we
      demonstrate that Notch1 up-regulates Runx1 expression and that the defective
      hematopoietic potential of Notch1-null P-Sp cells is successfully rescued in the
      OP9 culture system by retroviral transfer of Runx1. We also show that Hes1, a
      known effector of Notch signaling, potentiates Runx1-mediated transactivation.
      Together with the recent findings in zebrafish, Runx1 is postulated to be a
      cardinal down-stream mediator of Notch signaling in hematopoietic development
      throughout vertebrates. Our findings also suggest that Notch signaling may
      modulate both expression and transcriptional activity of Runx1.

PMID- 16888093
TI  - Differential effects of recombinant thrombopoietin and bone marrow stromal
      conditioned media on neonatal versus adult megakaryocytes.
AB  - Umbilical cord blood (CB) is a valuable source of stem cells for transplantation,
      but CB transplantations are frequently complicated by delayed platelet
      engraftment. The reasons underlying this are unclear. We hypothesized that CB-
      and peripheral-blood (PB)-derived megakaryocytes (MKs) respond differently to the
      adult hematopoietic microenvironment and to thrombopoietin (Tpo). To test this,
      we cultured CB- and PB-CD34(+) cells in adult bone marrow stromal conditioned
      media (CM) or unconditioned media (UCM) with increasing concentrations of
      recombinant Tpo and compared the effects of these conditions on CB-versus PB-MKs.
      PB-MKs reached highest ploidy in response to UCM + 100 ng/mL rTpo, and the
      addition of CM inhibited their maturation. In contrast, CB-MKs reached highest
      ploidy in CM without rTpo, and high rTpo concentrations (> 0.1 ng/mL) inhibited
      their maturation. This is the first evidence that human neonatal and adult MKs
      have substantially different biologic responses to Tpo and potentially to other
      cytokines.

PMID- 16888094
TI  - Humoral immunity is the dominant barrier for allogeneic bone marrow engraftment
      in sensitized recipients.
AB  - We evaluated the relative contribution of the humoral and cellular arms of the
      immune response to bone marrow cells transplanted into sensitized recipients. We
      report here for the first time that humoral immunity contributes predominantly to
      allosensitization. Although the major role for nonmyeloablative conditioning is
      to control alloreactive host T cells in nonsensitized recipients, strikingly,
      none of the strategies directed primarily at T-cell alloreactivity enhanced
      engraftment in sensitized mice. In evaluating the mechanism behind this barrier,
      we found that humoral immunity plays a critical role in the rejection of
      allogeneic marrow in sensitized recipients. Adoptive transfer of as little as 25
      microL serum from sensitized mice abrogated engraftment in secondary naive
      recipients. With the use of microMT mice as recipients, we found that T-cell
      mediated immunity plays a secondary but still significant role in allorejection.
      Targeting of T cells in sensitized B-cell-deficient microMT mice enhanced
      alloengraftment. Moreover, both T- and B-cell tolerance were achieved in
      sensitized recipients when allochimerism was established, as evidenced by the
      acceptance of second donor skin grafts and loss of circulating donor-specific
      Abs. These findings have important implications for the management of sensitized
      transplant recipients and for xenotransplantation in which B-cell reactivity is a
      predominant barrier.

PMID- 16888096
TI  - Protein tyrosine phosphatase receptor-type O truncated (PTPROt) regulates SYK
      phosphorylation, proximal B-cell-receptor signaling, and cellular proliferation.
AB  - The strength and duration of B-cell-receptor (BCR) signaling depends upon the
      balance between protein tyrosine kinase (PTK) activation and protein tyrosine
      phosphatase (PTP) inhibition. BCR-dependent activation of the SYK PTK initiates
      downstream signaling events and amplifies the original BCR signal. Although BCR
      associated SYK phosphorylation is clearly regulated by PTPs, SYK has not been
      identified as a direct PTP substrate. Herein, we demonstrate that SYK is a major
      substrate of a tissue-specific and developmentally regulated PTP, PTP receptor
      type O truncated (PTPROt). PTPROt is a member of the PTPRO family (also
      designated GLEPP, PTP-O, PTP-oc, and PTPu2), a group of highly conserved receptor
      type PTPs that are thought to function as tumor suppressor genes. The
      overexpression of PTPROt inhibited BCR-triggered SYK tyrosyl phosphorylation,
      activation of the associated adaptor proteins SHC and BLNK, and downstream
      signaling events, including calcium mobilization and mitogen-activated protein
      kinase/extracellular signal-regulated kinase (MAPK/ERK) activation. PTPROt
      overexpression also inhibited lymphoma cell proliferation and induced apoptosis
      in the absence of BCR cross-linking, suggesting that the phosphatase modulates
      tonic BCR signaling.

PMID- 16888097
TI  - Overlapping functions of human CD3delta and mouse CD3gamma in alphabeta T-cell
      development revealed in a humanized CD3gamma-mouse.
AB  - Humans lacking the CD3gamma subunit of the pre-TCR and TCR complexes exhibit a
      mild alphabeta T lymphopenia, but have normal T cells. By contrast, CD3gamma
      deficient mice are almost devoid of mature alphabeta T cells due to an early
      block of intrathymic development at the CD4(-)CD8(-) double-negative (DN) stage.
      This suggests that in humans but not in mice, the highly related CD3delta chain
      replaces CD3gamma during alphabeta T-cell development. To determine whether human
      CD3delta (hCD3delta) functions in a similar manner in the mouse in the absence of
      CD3gamma, we introduced an hCD3delta transgene in mice that were deficient for
      both CD3delta and CD3gamma, in which thymocyte development is completely arrested
      at the DN stage. Expression of hCD3delta efficiently supported pre-TCR-mediated
      progression from the DN to the CD4(+)CD8(+) double-positive (DP) stage. However,
      alphabetaTCR-mediated positive and negative thymocyte selection was less
      efficient than in wild-type mice, which correlated with a marked attenuation of
      TCR-mediated signaling. Of note, murine CD3gamma-deficient TCR complexes that had
      incorporated hCD3delta displayed abnormalities in structural stability resembling
      those of T cells from CD3gamma-deficient humans. Taken together, these data
      demonstrate that CD3delta and CD3gamma play a different role in humans and mice
      in pre-TCR and TCR function during alphabeta T-cell development.

PMID- 16888095
TI  - CCL18/PARC stimulates hematopoiesis in long-term bone marrow cultures indirectly
      through its effect on monocytes.
AB  - Chemokines play a role in regulating hematopoietic stem cell function, including
      migration, proliferation, and retention. We investigated the involvement of CCL18
      in the regulation of bone marrow hematopoiesis. Treatment of human long-term bone
      marrow cultures (LTBMCs) with CCL18 resulted in significant stimulation of
      hematopoiesis, as measured by the total number of hematopoietic cells and their
      committed progenitors produced in culture. Monocytes/macrophages, whose survival
      was almost doubled in the presence of CCL18 compared with controls, were the
      primary cells mediating this effect. Conditioned media from CCL18-treated mature
      monocytes fostered colony-promoting activity that increased the number of
      colonies formed by hematopoietic progenitor cells. Gene expression profiling of
      CCL18-stimulated monocytes demonstrated more than 200 differentially expressed
      genes, including those regulating apoptosis (caspase-8) and proliferation (IL-6,
      IL-15, stem cell factor [SCF]). Up-regulation of these cytokines was confirmed on
      the protein expression level. The contribution of SCF and IL-6 in CCL18-mediated
      stimulatory activity for hematopoiesis was confirmed by SCF- and IL-6-blocking
      antibodies that significantly inhibited the colony-promoting activity of CCL18
      stimulated conditioned medium. In addition to the effect on monocytes, CCL18
      facilitated the formation of the adherent layer in LTBMCs and increased the
      proliferation of stromal fibroblast-like cells.

PMID- 16888098
TI  - Prolonged bleeding-free period following prophylactic infusion of recombinant
      factor VIII reconstituted with pegylated liposomes.
AB  - Prophylactic treatment for hemophilia A involves infusion of factor VIII (FVIII)
      concentrates every 2 to 3 days. Liposomes can be efficacious vehicles for
      medicines, and surface modification by PEGylation can prolong liposome
      circulation time. When reconstituted with PEGylated liposomes (PEGLip's),
      recombinant FVIII binds noncovalently but with high affinity to the external
      liposome surface. This preparation showed prolongation of FVIII half-life and
      increased protection from bleeding in preclinical models. Here we report a
      blinded, controlled, crossover, multicenter clinical study that evaluated the
      time free from bleeding episodes in patients with hemophilia A during prophylaxis
      with standard rFVIII (no liposomes) or PEGLip rFVIII (PEGLip reconstituted) at 25
      and 35 IU/kg doses. Of 24 enrolled patients, 23 were eligible for efficacy
      analysis. Mean number of days without bleeds was 7.2 +/- 1.7 with standard rFVIII
      compared with 13.3 +/- 4.8 with PEGLip rFVIII at the 35 IU/kg dose and 5.9 +/-
      1.7 with standard rFVIII versus 10.9 +/- 2.9 with PEGLip rFVIII at the 25 IU/kg
      dose (P < .05 between treatment groups for each dose). PEGLip rFVIII was well
      tolerated. These data suggest that reconstitution of rFVIII with PEGLip's may
      reduce the frequency of treatment during prophylaxis.

PMID- 16888099
TI  - Diminished proteasomal degradation results in accumulation of Gfi1 protein in
      monocytes.
AB  - Gfi1 is a transcriptional repressor essential during myeloid differentiation.
      Gfi1-/- mice exhibit a block in myeloid differentiation resulting in the
      accumulation of an immature myelo-monocytic cell population and the complete
      absence of mature neutrophils. Even though mRNA levels of Gfi1 appear to be very
      low in monocytes, Gfi1 might play a role in the monocytic lineage as Gfi1-/- mice
      exhibit diminished monocyte-derived dendritic cells and disturbed cytokine
      production by macrophages in response to LPS. We show here that Gfi1 protein
      levels are mainly regulated by the ubiquitin-proteasome system. Upon forced
      monocytic differentiation of U937 cells, Gfi1 mRNA levels dropped but protein
      levels increased due to diminished proteasomal turnover. Similarly, Gfi1 mRNA
      levels are low in primary monocytes whereas the protein is clearly detectable.
      Conversely, Gfi1 mRNA levels are high in granulocytes but the protein is swiftly
      degraded by the proteasome in these cells. Chromatin immunoprecipitation
      experiments showed that Gfi1 binds to the promoter of several granulocyte
      specific genes in primary monocytes, including C/EBPalpha, neutrophil elastase,
      and Gfi1 itself. The binding of the repressor Gfi1 to these promoters correlated
      with low expression of these genes in monocytes compared with granulocytes. Our
      data fit a model in which Gfi1 protein levels are induced in primary monocytes,
      due to diminished proteasomal degradation, to repress genes that play a role in
      granulocytic differentiation.

PMID- 16888101
TI  - Discovery of a young planetary-mass binary.
AB  - We have identified a companion to the young planetary-mass brown dwarf Oph 162225
      240515. This pair forms a resolved binary consisting of two objects with masses
      comparable to those of extrasolar giant planets. Several lines of evidence
      confirm the coevality and youth of the two objects, suggesting that they form a
      physical binary. Models yield masses of approximately 14 and approximately 7
      times the mass of Jupiter for the primary and the secondary object, respectively,
      at an age of approximately 1 million years. A wide ( approximately 240
      astronomical unit) binary in the ultra-low-mass regime poses a challenge to some
      popular models of brown dwarf formation.

PMID- 16888100
TI  - STAT3 governs distinct pathways in emergency granulopoiesis and mature
      neutrophils.
AB  - Granulocyte colony-stimulating factor (G-CSF) is essential for the host response
      to bacterial infection by controlling neutrophil production in the bone marrow.
      The G-CSF receptor (G-CSFR) activates the Jak/STAT pathway, although little is
      understood about how these signals regulate basal and stress-induced
      granulopoiesis. We examined STAT3 function in granulocytes using a bone marrow
      conditional knockout mouse model. Our results show that STAT3 has a crucial role
      in emergency granulopoiesis and mature neutrophil function. STAT3-deficient mice
      have an aberrant response to G-CSF in vivo, characterized by failure to
      accumulate immature granulocytes and an increased ratio of mature to immature
      neutrophils in the bone marrow, peripheral blood, and spleen. Acute neutrophil
      mobilization is impaired in STAT3-deficient mice as judged by their failure to up
      regulate circulating neutrophils following short-term G-CSF exposure. STAT3 also
      controls neutrophil chemotactic responses to natural ligands for CXCR2 and
      regulates the magnitude of chemoattractant-induced actin polymerization. These
      functions of STAT3 are independent of its principal target gene Socs3, which
      encodes a crucial feedback inhibitor of cytokine signaling. Our results
      demonstrate the existence of distinct STAT3 target pathways in neutrophils
      required for granulopoiesis and innate immunity.

PMID- 16888102
TI  - Manipulation of host hepatocytes by the malaria parasite for delivery into liver
      sinusoids.
AB  - The merozoite stage of the malaria parasite that infects erythrocytes and causes
      the symptoms of the disease is initially formed inside host hepatocytes. However,
      the mechanism by which hepatic merozoites reach blood vessels (sinusoids) in the
      liver and escape the host immune system before invading erythrocytes remains
      unknown. Here, we show that parasites induce the death and the detachment of
      their host hepatocytes, followed by the budding of parasite-filled vesicles
      (merosomes) into the sinusoid lumen. Parasites simultaneously inhibit the
      exposure of phosphatidylserine on the outer leaflet of host plasma membranes,
      which act as "eat me" signals to phagocytes. Thus, the hepatocyte-derived
      merosomes appear to ensure both the migration of parasites into the bloodstream
      and their protection from host immunity.

PMID- 16888104
TI  - The G8 on energy: too little.

PMID- 16888105
TI  - Scientific publishing. The undisclosed background of a paper on a depression
      treatment.

PMID- 16888103
TI  - Human IRGM induces autophagy to eliminate intracellular mycobacteria.
AB  - Immunity-related p47 guanosine triphosphatases (IRG) play a role in defense
      against intracellular pathogens. We found that the murine Irgm1 (LRG-47)
      guanosine triphosphatase induced autophagy and generated large autolysosomal
      organelles as a mechanism for the elimination of intracellular Mycobacterium
      tuberculosis. We also identified a function for a human IRG protein in the
      control of intracellular pathogens and report that the human Irgm1 ortholog,
      IRGM, plays a role in autophagy and in the reduction of intracellular bacillary
      load.

PMID- 16888106
TI  - Planetary science. At last, methane lakes on Saturn's icy moon Titan--but no
      seas.

PMID- 16888107
TI  - Earth science. China grapples with seismic risk in its northern heartland.

PMID- 16888108
TI  - International science. Singapore-Hopkins partnership ends in a volley of fault
      finding.

PMID- 16888109
TI  - Neuroscience. The emotional brain weighs its options.

PMID- 16888111
TI  - Physics. High-temperature superconductors feel the vibe after all.

PMID- 16888110
TI  - Avian influenza. Hybrid viruses fail to spread.

PMID- 16888112
TI  - Physics. Physicists see solid helium flow, but not in the most exciting way.

PMID- 16888113
TI  - Sociology. Making connections.

PMID- 16888114
TI  - Sociology. Looking for patterns.

PMID- 16888116
TI  - Climate research. Waiting for the monsoon.

PMID- 16888115
TI  - Solar physics. Space weather forecasters plan a boost in surveillance missions.

PMID- 16888118
TI  - Boycott of Israeli academics misguided.

PMID- 16888117
TI  - U.S. Homeland Security. Congress dials back research on understanding terrorism.

PMID- 16888119
TI  - Keeping bandits at bay?

PMID- 16888120
TI  - Making U.S. graduate education more diverse.

PMID- 16888121
TI  - Recognizing computational science.

PMID- 16888122
TI  - Comment on "Post-wildfire logging hinders regeneration and increases fire risk".
AB  - Donato et al. (Brevia, 20 January 2006, p. 352) concluded that logging after
      wildfire kills natural regeneration and increases fire risk. We argue that their
      paper lacks adequate context and supporting information to be clearly interpreted
      by scientists, resource managers, policy-makers, and the public.

PMID- 16888123
TI  - Comment on "Post-wildfire logging hinders regeneration and increases fire risk".
AB  - Based on limited sampling 2 years after the 2002 Biscuit Fire in Oregon, Donato
      et al. (Brevia, 20 January 2006, p. 352) concluded that postfire logging reduced
      seedling regeneration by 71%. Analysis of the study methodology and raw data
      suggest that this estimate is statistically flawed and misleading and says
      nothing about the impacts of more prompt postfire harvest.

PMID- 16888124
TI  - Sustainability. Resolving mismatches in U.S. ocean governance.

PMID- 16888125
TI  - Geophysics. A new class of earthquake observations.

PMID- 16888126
TI  - Climate. Caving in to new chronologies.

PMID- 16888127
TI  - Planetary science. Solving Laplace's lunar puzzle.

PMID- 16888128
TI  - Climate. How do aerosols affect cloudiness and climate?

PMID- 16888129
TI  - Cell biology. Extinguishing a cell cycle checkpoint.

PMID- 16888130
TI  - Microbiology. Timing the sexual development of parasites.

PMID- 16888131
TI  - Immunology. Sugar determines antibody activity.

PMID- 16888132
TI  - The primary cilium as the cell's antenna: signaling at a sensory organelle.
AB  - Almost every vertebrate cell has a specialized cell surface projection called a
      primary cilium. Although these structures were first described more than a
      century ago, the full scope of their functions remains poorly understood. Here,
      we review emerging evidence that in addition to their well-established roles in
      sight, smell, and mechanosensation, primary cilia are key participants in
      intercellular signaling. This new appreciation of primary cilia as cellular
      antennae that sense a wide variety of signals could help explain why ciliary
      defects underlie such a wide range of human disorders, including retinal
      degeneration, polycystic kidney disease, Bardet-Biedl syndrome, and neural tube
      defects.

PMID- 16888134
TI  - Imaging the Mott insulator shells by using atomic clock shifts.
AB  - Microwave spectroscopy was used to probe the superfluid-Mott insulator transition
      of a Bose-Einstein condensate in a three-dimensional optical lattice. By using
      density-dependent transition frequency shifts, we were able to spectroscopically
      distinguish sites with different occupation numbers and to directly image sites
      with occupation numbers from one to five, revealing the shell structure of the
      Mott insulator phase. We used this spectroscopy to determine the onsite
      interaction and lifetime for individual shells.

PMID- 16888133
TI  - Fibrin fibers have extraordinary extensibility and elasticity.
AB  - Blood clots perform an essential mechanical task, yet the mechanical behavior of
      fibrin fibers, which form the structural framework of a clot, is largely unknown.
      By using combined atomic force-fluorescence microscopy, we determined the elastic
      limit and extensibility of individual fibers. Fibrin fibers can be strained 180%
      (2.8-fold extension) without sustaining permanent lengthening, and they can be
      strained up to 525% (average 330%) before rupturing. This is the largest
      extensibility observed for protein fibers. The data imply that fibrin monomers
      must be able to undergo sizeable, reversible structural changes and that
      deformations in clots can be accommodated by individual fiber stretching.

PMID- 16888135
TI  - Evidence for a past high-eccentricity lunar orbit.
AB  - The large differences between the Moon's three principal moments of inertia have
      been a mystery since Laplace considered them in 1799. Here we present
      calculations that show how past high-eccentricity orbits can account for the
      moment differences, represented by the low-order lunar gravity field and
      libration parameters. One of our solutions is that the Moon may have once been in
      a 3:2 resonance of orbit period to spin period, similar to Mercury's present
      state. The possibility of past high-eccentricity orbits suggests a rich dynamical
      history and may influence our understanding of the early thermal evolution of the
      Moon.

PMID- 16888136
TI  - Crustal dilatation observed by GRACE after the 2004 Sumatra-Andaman earthquake.
AB  - We report the detection of an earthquake by a space-based measurement. The
      Gravity Recovery and Climate Experiment (GRACE) satellites observed a +/-15
      microgalileo gravity change induced by the great December 2004 Sumatra-Andaman
      earthquake. Coseismic deformation produces sudden changes in the gravity field by
      vertical displacement of Earth's layered density structure and by changing the
      densities of the crust and mantle. GRACE's sensitivity to the long spatial
      wavelength of gravity changes resulted in roughly equal contributions of vertical
      displacement and dilatation effects in the gravity measurements. The GRACE
      observations provide evidence of crustal dilatation resulting from an undersea
      earthquake.

PMID- 16888137
TI  - Synthesis of biaryls via catalytic decarboxylative coupling.
AB  - We present a safe and convenient cross-coupling strategy for the large-scale
      synthesis of biaryls, commercially important structures often found in
      biologically active molecules. In contrast to traditional cross-couplings, which
      require the prior preparation of organometallic reagents, we use a copper
      catalyst to generate the carbon nucleophiles in situ, via decarboxylation of
      easily accessible arylcarboxylic acid salts. The scope and potential economic
      impact of the reaction are demonstrated by the synthesis of 26 biaryls, one of
      which is an intermediate in the large-scale production of the agricultural
      fungicide Boscalid.

PMID- 16888138
TI  - Gender differences in patenting in the academic life sciences.
AB  - We analyzed longitudinal data on academic careers and conducted interviews with
      faculty members to determine the scope and causes of the gender gap in patenting
      among life scientists. Our regressions on a random sample of 4227 life scientists
      over a 30-year period show that women faculty members patent at about 40% of the
      rate of men. We found that the gender gap has improved over time but remains
      large.

PMID- 16888139
TI  - Regulation of sexual development of Plasmodium by translational repression.
AB  - Translational repression of messenger RNAs (mRNAs) plays an important role in
      sexual differentiation and gametogenesis in multicellular eukaryotes.
      Translational repression and mRNA turnover were shown to influence stage-specific
      gene expression in the protozoan Plasmodium. The DDX6-class RNA helicase, DOZI
      (development of zygote inhibited), is found in a complex with mRNA species in
      cytoplasmic bodies of female, blood-stage gametocytes. These translationally
      repressed complexes are normally stored for translation after fertilization.
      Genetic disruption of pbdozi inhibits the formation of the ribonucleoprotein
      complexes, and instead, at least 370 transcripts are diverted to a degradation
      pathway.

PMID- 16888140
TI  - Anti-inflammatory activity of immunoglobulin G resulting from Fc sialylation.
AB  - Immunoglobulin G (IgG) mediates pro- and anti-inflammatory activities through the
      engagement of its Fc fragment (Fc) with distinct Fcg receptors (FcgRs). One class
      of Fc-FcgR interactions generates pro-inflammatory effects of immune complexes
      and cytotoxic antibodies. In contrast, therapeutic intravenous gamma globulin and
      its Fc fragments are anti-inflammatory. We show here that these distinct
      properties of the IgG Fc result from differential sialylation of the Fc core
      polysaccharide. IgG acquires anti-inflammatory properties upon Fc sialylation,
      which is reduced upon the induction of an antigen-specific immune response. This
      differential sialylation may provide a switch from innate anti-inflammatory
      activity in the steady state to generating adaptive pro-inflammatory effects upon
      antigenic challenge.

PMID- 16888141
TI  - N- to C-terminal SNARE complex assembly promotes rapid membrane fusion.
AB  - Assembly of the soluble N-ethylmaleimide-sensitive factor attachment protein
      receptors (SNAREs) syntaxin 1, SNAP-25, and synaptobrevin 2 is thought to be the
      driving force for the exocytosis of synaptic vesicles. However, whereas
      exocytosis is triggered at a millisecond time scale, the SNARE-mediated fusion of
      liposomes requires hours for completion, which challenges the idea of a key role
      for SNAREs in the final steps of exocytosis. We found that liposome fusion was
      dramatically accelerated when a stabilized syntaxin/SNAP-25 acceptor complex was
      used. Thus, SNAREs do have the capacity to execute fusion at a speed required for
      neuronal secretion, demonstrating that the maintenance of acceptor complexes is a
      critical step in biological fusion reactions.

PMID- 16888144
TI  - Editorial independence for CMAJ: signposts along the road.

PMID- 16888142
TI  - Frames, biases, and rational decision-making in the human brain.
AB  - Human choices are remarkably susceptible to the manner in which options are
      presented. This so-called "framing effect" represents a striking violation of
      standard economic accounts of human rationality, although its underlying
      neurobiology is not understood. We found that the framing effect was specifically
      associated with amygdala activity, suggesting a key role for an emotional system
      in mediating decision biases. Moreover, across individuals, orbital and medial
      prefrontal cortex activity predicted a reduced susceptibility to the framing
      effect. This finding highlights the importance of incorporating emotional
      processes within models of human choice and suggests how the brain may modulate
      the effect of these biasing influences to approximate rationality.

PMID- 16888146
TI  - Clues to VIP function from knockout mice.
AB  - We have taken advantage of the availability of vasoactive intestinal polypeptide
      (VIP) knockout (KO) mice to examine the possible influence of deletion of the VIP
      gene on: (a) airway reactivity and airway inflammation, as indicators of
      bronchial asthma; (b) mortality from endotoxemia, a model of septic shock; and
      (c) the pulmonary circulation. VIP KO mice showed: (a) airway hyperresponsiveness
      to the cholinergic agonist methacholine, as well as peribronchial and
      perivascular inflammation; (b) a greater susceptibility to death from
      endotoxemia; and (c) evidence suggestive of pulmonary hypertension.

PMID- 16888145
TI  - Treatment of renal failure associated with multiple myeloma and other diseases by
      PACAP-38.
AB  - Myeloma kidney injury is caused by the large amount of light chain (LC) of
      immunoglobulins produced by cancerous plasma cells through stimulation of
      proinflamatory cytokines like TNF-alpha and IL-6. PACAP-38 suppressed LC
      stimulated cytokine production by tubular epithelial cells in vitro and in vivo,
      and prevented injury of these epithelial cells. The suppressive effect is
      comparable or greater than dexamethasone (dex). Although dex produces adverse
      side effects when it is given for a long time period, PACAP-38 is a natural and
      safe neuropeptide and no adverse effect has been reported when administered to
      produce significant biological effects. Furthermore, PACAP-38 suppressed growth
      of myeloma cells in culture and also suppressed production of their growth
      factor, IL-6, production from the bone marrow stromal cells that was stimulated
      by adhesion of myeloma cells. These findings render PACAP-38 worth evaluation as
      a safe and potent renoprotectant in myeloma kidney as well as a new antitumor
      agent for myeloma cells.

PMID- 16888147
TI  - The glucagon-like peptides: pleiotropic regulators of nutrient homeostasis.
AB  - The glucagon-like peptides, GLP-1 and GLP-2, are cosecreted by intestinal L cells
      in response to nutrient ingestion. These peptides exert multiple effects on the
      gastrointestinal tract and pancreas to regulate the digestion, absorption, and
      assimilation of ingested nutrients, as well as providing feedback signals to the
      brain to modulate food intake. Tropic effects of GLP-1 and GLP-2 on their major
      peripheral target tissues, the beta cell and the intestinal epithelium,
      respectively, further enhance capacity for nutrient handling. When taken
      together, these findings demonstrate the diverse actions of the intestinal
      glucagon-like peptides to regulate nutrient homeostasis.

PMID- 16888148
TI  - Secretin: a pleiotrophic hormone.
AB  - Secretin holds a unique place in the history of endocrinology and
      gastrointestinal physiology, as it is the first peptide designated as a hormone.
      During the last century since its first discovery, the hormonal effects of
      secretin in the gastrointestinal tract were extensively studied, and its
      principal role in the periphery was found to stimulate exocrine secretion from
      the pancreas. Recently, a functional role of secretin in the brain has also been
      substantiated, with evidence suggesting a possible role of secretin in embryonic
      brain development. Given that secretin and its receptors are widely expressed in
      multiple tissues, this peptide should therefore exhibit pleiotrophic functions
      throughout the body. The present article reviews the current knowledge on the
      central and peripheral effects of secretin as well as its therapeutic uses.

PMID- 16888149
TI  - VIP-PACAP system in immunity: new insights for multitarget therapy.
AB  - Our research about VIP/PACAP and the immune system goes back to 1990 when our
      group described the expression of VIP on lymphocytes for the first time. Since
      this year, using three models of disease, septic shock, rheumathoid arthritis,
      and Crohn's disease, we are trying to contribute with new pieces to the puzzle of
      immunity to approach the use of VIP/PACAP system as a therapeutic agent. In 1999
      we established that the first step in the beneficial effect of the VIP/PACAP
      system exerts consists in its potent anti-inflammatory action. Thus, VIP and
      PACAP inhibit the expression and release of proinflammatory cytokines and
      chemokines, and enhance the production of the anti-inflammatory factors. These
      effects were reported both in vitro and in vivo, are mediated by the presence of
      PAC1, VPAC1, and VPAC2 receptors, in the three models of diseases used. The next
      step was that the system favors Th2 responses versus Th1 contributing to the
      remission of illness as rheumatoid arthritis or Crohn's disease by blocking the
      autoimmune component of these diseases. Because it appears that inflammatory
      processes requires more than blockade of a single mediator, new therapies
      blocking several components of both the infection- and the autoimmunity-induced
      inflammation cascades should be an interesting focus of attention. In this sense,
      at present we are trying to dissect new aspects of the potential therapeutic of
      the VIP/PACAP system in the control of CC and CXC chemokine and their receptors,
      coagulation factors, adhesion molecules, acute phase proteins, and
      osteoclastogenesis mediators as well as in the modulation of the expression of
      Toll-like receptors. Our more recent data open a hopeful door for the therapeutic
      use of VIP/PACAP in humans.

PMID- 16888150
TI  - New insights into the central PACAPergic system from the phenotypes in PACAP- and
      PACAP receptor-knockout mice.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) is a structurally
      highly conserved neuropeptide and displays pleiotropic activity, including
      functioning as a neurotransmitter, neuromodulator, and neurotrophic factor. A
      series of recent experiments, including genetic manipulation of PACAP and its
      receptors, has led to better understanding of both normal and pathological
      processes in which PACAP has been proposed to play a role, and sheds light on
      previously uncharacterized functions of endogenous PACAP. The aim of this article
      is to briefly review the recent advances in understanding the role of PACAP in
      the central nervous system from PACAP- and PACAP receptor-deficient mice,
      particularly with respect to behavioral and neurological features, including
      psychomotor behavior, feeding, stress responses, memory performance, ethanol
      sensitivity, chronic pain, and circadian rhythms. This article also discusses
      their potential involvement in human diseases.

PMID- 16888151
TI  - Complexing receptor pharmacology: modulation of family B G protein-coupled
      receptor function by RAMPs.
AB  - The most well-characterized subgroup of family B G protein-coupledreceptors
      (GPCRs) comprises receptors for peptide hormones, such as secretin, calcitonin
      (CT), glucagon, and vasoactive intestinal peptide (VIP). Recent data suggest that
      many of these receptors can interact with a novel family of GPCR accessory
      proteins termed receptor activity modifying proteins (RAMPs). RAMP interaction
      with receptors can lead to a variety of actions that include chaperoning of the
      receptor protein to the cell surface as is the case for the calcitonin receptor
      like receptor (CLR) and the generation of novel receptor phenotypes. RAMP
      heterodimerization with the CLR and related CT receptor is required for the
      formation of specific CT gene-related peptide, adrenomedullin (AM) or amylin
      receptors. More recent work has revealed that the specific RAMP present in a
      heterodimer may modulate other functions such as receptor internalization and
      recycling and also the strength of activation of downstream signaling pathways.
      In this article we review our current state of knowledge of the consequence of
      RAMP interaction with family B GPCRs.

PMID- 16888152
TI  - The three-dimensional structure of the N-terminal domain of corticotropin
      releasing factor receptors: sushi domains and the B1 family of G protein-coupled
      receptors.
AB  - The corticotropin-releasing factor (CRF) receptors, CRF-R1 and CRF-R2, belong to
      the B1 subfamily of G protein-coupled Receptors (GPCRs), including receptors for
      secretin, growth hormone-releasing hormone (GHRH), vasoactive intestinal peptide
      (VIP), pituitary adenylate cyclase-activating polypeptide (PACAP), calcitonin,
      parathyroid hormone (PTH), glucagon, and glucagon-like peptide-1 (GLP-1). The
      peptide ligand family comprises CRF, Ucn 1, 2, and 3. CRF plays the major role in
      integrating the response to stress. Additionally, the ligands exhibit many
      effects on muscle, pancreas, heart, and the GI, reproductive, and immune systems.
      CRF-R1 has higher affinity for CRF than does CRF-R2 while both receptors bind Ucn
      1 equally. CRF-R2 shows specificity for Ucns 2 and 3. A major binding domain of
      the CRFRs is the N terminus/first extracellular domain (ECD1). Soluble proteins
      corresponding to the ECD1s of each receptor bind CRF ligands with nanomolar
      affinities. Our three-dimensional (3D) nuclear magnetic resonance (NMR) structure
      of a soluble protein corresponding to the ECD1 of CRF-R2beta (1) identified its
      structural fold as a Sushi domain/short consensus repeat (SCR), stabilized by
      three disulfide bridges, two tryptophan residues, and an internal salt bridge
      (Asp65-Arg101). Disruption of the bridge by D65A mutation abrogates ligand
      recognition and results in loss of the well-defined disulfide pattern and Sushi
      domain structure. NMR analysis of the ECD1 in complex with astressin identified
      key amino acids involved in ligand recognition. Mutation of some of these
      residues in the full-length receptor reduces its affinity for CRF ligands. A
      structure-based sequence comparison shows conservation of key amino acids in all
      the B1 subfamily receptors, suggesting a corresponding conservation of a Sushi
      domain structural fold of their ECD1s.

PMID- 16888153
TI  - Hedgehog signaling: new targets for GPCRs coupled to cAMP and protein kinase A.
AB  - Hedgehog (HH) is a secreted protein named for the bristle phenotype observed in
      Drosophila embryos that lack the corresponding gene. Three homologs have been
      characterized in vertebrates, all which have critical roles in the development of
      multiple organ systems. Moreover, these proteins regulate stem cell production
      and activation during tissue repair after injury, and appear to drive
      proliferation in a variety of type of tumors, including those arising in the
      brain, foregut, lung, breast, pancreas, stomach, and prostate. Early evidence
      from Drosophila, and later work in vertebrates established the cAMP/protein
      kinase A (PKA) pathway as a major pathway which opposes HH signaling, doing so by
      phosphorylating intracellular signaling mediators and targeting them for
      degradation. Thus, it seems possible that ligands which activate G protein
      coupled receptors (GPCR) may act in some cases to oppose or enhance HH signaling.
      We studied a possible interaction of pituitary adenylyl cyclase-activating
      peptide (PACAP) with sonic hedgehog (SHH) in the developing cerebellum, where
      both PACAP and SHH are know to act. PACAP and the PAC1-specific agonist,
      maxadilan, were found to completely block the proliferative action of SHH on
      developing cerebellar granule neurons. It remains to be determined if HH/GPCR
      antagonistic interactions play additional important roles in development,
      plasticity, tissue repair, cancer, and other processes.

PMID- 16888155
TI  - Immunocytochemical distribution of VIP and PACAP in the rat brain stem:
      implications for REM sleep physiology.
AB  - Recent evidence indicates that pituitary adenylate cyclase-activating polypeptide
      (PACAP) and vasoactive intestinal polypeptide (VIP) might play an important role
      in rapid eye movement sleep (REMS) generation at the pontine level in rats. We
      have thus examined the immunohistochemical distribution of VIP and PACAP in the
      pontine and mesencephalic areas known to be involved in REMS control in rats. A
      dense network of VIP-immunoreactive cell bodies and fibers was found in the
      dorsal raphe nucleus. A large number of PACAP-positive perikarya and nerve fibers
      was observed in the area known as the REMS induction zone within the pontine
      reticular formation (PRF). The present results provide an anatomical basis to our
      previous functional data, and suggest that PACAPergic mechanisms within the PRF
      play a critical role in long-term regulation of REMS.

PMID- 16888154
TI  - Effect of VIP on TLR2 and TLR4 expression in lymph node immune cells during TNBS
      induced colitis.
AB  - Toll-like receptors (TLRs) are a family of pattern recognition receptors (PRRs),
      which recognize numerous molecules collectively named pathogen-associated
      molecular patterns, with an essential role in inflammatory conditions and
      connecting innate and acquired immune responses. Moreover, a new function of TLRs
      in the intestinal mucosa has been described. Under homeostatic conditions, TLRs
      act to protect the intestinal epithelium; but when homeostasis is disrupted, TLRs
      appear deregulated. Disruption of intestinal homeostasis occurs in disorders,
      such as Crohn's disease (CD). Trinitrobenzene sulfonic acid (TNBS)-induced
      colitis is a murine model of human CD and vasoactive intestinal polypeptide (VIP)
      exerts a beneficial effect, by decreasing both inflammatory and autoimmune
      components of the disease. Recently, we have demonstrated the constitutive
      expression of TLR2 and TLR4 at mRNA and protein levels in colon extracts and
      their upregulation in TNBS-treated mice as well as the effect of VIP treatment,
      approaching control levels. However, the systemic effect is little known. The
      present results demonstrate a beneficial role of VIP, restoring homeostatic
      conditions through the regulation of both lymphoid cell traffic and TLR2/4
      expression on macrophages (MO), dendritic cells (DCs), and CD4 and CD8 T
      lymphocytes.

PMID- 16888156
TI  - Microiontophoretically applied PACAP blocks excitatory effects of kainic acid in
      vivo.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) has been shown to be
      neuroprotective in animal models of different brain pathologies, including focal
      and global cerebral ischemia. The application of glutaminergic excitotoxin kainic
      acid (KA), similar to ischemic events, may lead to neurodegeneration. In the
      present article, we investigated the effects of microiontophoretic application of
      PACAP on the excitatory effects of KA. During recording-maintained spontaneous
      activity of single neurons, we microiontophoretized KA, which was followed by the
      application of PACAP-38. We found that PACAP could block the excitatory effects
      of KA in several brain areas (cortex: 89%, hippocampus: 36%, and thalamus: 50%).
      Moreover, we detected a lower level excitatory effect of PACAP alone (41%). The
      present results may explain the neuroprotective effects of PACAP observed in
      experimental models of glutamate (GLU)-receptor-mediated degenerative processes.

PMID- 16888157
TI  - Search for the optimal monosodium glutamate treatment schedule to study the
      neuroprotective effects of PACAP in the retina.
AB  - We have previously shown the protective effects of pituitary adenylate
      cyclaseactivating polypeptide (PACAP) in monosodium glutamate (MSG)-induced
      retinal degeneration. In the present article, we have investigated the optimal
      model for examining this neuroprotective effect. One MSG treatment on postnatal
      (P) days 1 or 5, in spite of leading to same ultrastructural changes, does not
      cause enough damage to study neuroprotection. When retinas were treated three
      times with MSG, the entire inner retina degenerated. Neuroprotection with PACAP
      was achieved with at least two treatments. Evidence suggests that PACAP provides
      protection against excitotoxicity, therefore, it may be a useful agent in
      reducing excitotoxic damage in the retina.

PMID- 16888158
TI  - Can PACAP-38 modulate immune and endocrine responses during lipopolysaccharide
      (LPS)-induced acute inflammation?
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) shows a potential anti
      inflammatory activity and interacts with the endocrine system. The aim of the
      present article was to evaluate the effects of PACAP38 on the endocrine and
      immune systems during acute inflammation. Rats used in the experiments, divided
      into four groups, were given intraperitoneal injection of, respectively 0.9%
      NaCl, LPS, PACAP38, and LPS+PACAP38. Hormone (pituitary, adrenal, and thyroid)
      and cytokine (TNF-alpha, IL-6, IL10) concentrations were measured 2 and 4 h after
      the injection. Treatment with LPS + PACAP, as compared to LPS, caused TNF-alpha
      and corticosterone to decrease and T4 to increase after 2 h. These data suggest
      that PACAP modulates both the endocrine and immune responses in this model of
      septic shock.

PMID- 16888159
TI  - The glucagon-miniglucagon interplay: a new level in the metabolic regulation.
AB  - Miniglucagon (glucagon 19-29) is the ultimate processing product of proglucagon,
      present in the glucagon-secreting granules of the alpha cells, at a close
      vicinity of the insulin-secreting beta cells. Co-released with glucagon and
      thanks to its original mode of action and its huge potency, it suppresses, inside
      the islet of Langerhans, the detrimental effect of glucagon on insulin secretion,
      while it leaves untouched the beneficial effect of glucagon on glucose competence
      of the beta cell. At the periphery, miniglucagon is processed at the surface of
      glucagon- and insulin-sensitive cells from circulating glucagon. At that level,
      it acts via a cellular pathway which uses initial molecular steps distinct from
      that of insulin which, when impaired, are involved in insulin resistence. This
      bypass allows miniglucagon to act as an insulin-like component, a characteristic
      which makes this peptide of particular interest from a pathophysiological and
      pharmacological point of views in understanding and treating metabolic diseases,
      such as the type 2 diabetes.

PMID- 16888160
TI  - Effects of VIP and VIP-DAP on proliferation and lipid peroxidation metabolism in
      human KB cells.
AB  - In the present study, we have utilized the transglutaminase (TGase) enzyme to
      modify the primary structure of VIP with diaminopropane (DAP) at the level of the
      Gln16. We have investigated the conformational stability of VIP and VIP-DAP in
      solution by limited proteolysis experiments. The VIP-DAP appears to be more
      resistant to the proteolytic attack of trypsin, thus indicating that the
      derivatization in position 16 is able to stabilize the structure of the peptide.
      However, we have studied their role in cell cycle modulation and antioxidant
      activity in the oropharyngeal epidermoid carcinoma KB cells.

PMID- 16888162
TI  - Spatial approximation between the C-terminus of VIP and the N-terminal ectodomain
      of the VPAC1 receptor.
AB  - Vasoactive intestinal peptide (VIP) exerts many biological functions through
      interaction with the VPAC1 receptor, a class II G protein-coupled receptor.
      Photoaffinity labeling studies associated with receptor mapping and three
      dimensional molecular modeling demonstrated that the central part of VIP (6-24)
      interacts with the N-terminal ectodomain of VPAC1 receptor. However, the domain
      of the VPAC1 receptor interacting with the C-terminus of VIP is still unknown. A
      photoaffinity probe, Bpa28-VIP, was synthetized by substitution of amidated Asn28
      of VIP by amidated photoreactive para-benzoyl-L-Phe (Bpa). Bpa28-VIP was shown to
      be a hVPAC1 receptor agonist in CHO cells expressing the recombinant VPAC1
      receptor. After obtaining a covalent 125I-[Bpa28-VIP]/hVPAC1 complex, it was
      cleaved by CNBr, PNGase F, and endopeptidase Glu-C and the cleavage products were
      analyzed by electrophoresis. The data demonstrated that 125I-[Bpa28-VIP] was
      covalently bonded to the 121-133 fragment within the N-terminal ectodomain of the
      receptor. This fragment is adjacent to those covalently attached to the central
      part (6-24) of VIP.

PMID- 16888161
TI  - The delayed rectifier channel current IK plays a key role in the control of
      programmed cell death by PACAP and ethanol in cerebellar granule neurons.
AB  - Alcohol exposure during development causes severe brain malformations, and thus,
      identification of molecules that can counteract the neurotoxicity of ethanol
      deserves high priority. Since activation of potassium (K+) currents has been
      shown to play a critical role in the control of programmed cell death, we have
      investigated the effects of ethanol and PACAP on K+ currents in cultured
      cerebellar granule cells using the patch-clamp technique in the whole cell
      configuration. In the presence of the fast-inactivating IA current blocker 4-AP,
      a focal application of ethanol (200 mM) in the vicinity of granule cells provoked
      a robust hyperpolarization and a marked increase of the delayed rectifier IK
      current. Addition of PACAP (0.1 microM) in the bath solution prevented ethanol
      induced membrane hyperpolarization and suppressed the stimulatory effect of
      ethanol on IK current. These data suggest that ethanol alters neuronal survival,
      at least in part, through activation of IK, and that PACAP abolishes ethanol
      induced cerebellar granule cell death via inhibition of IK..

PMID- 16888163
TI  - PACAP and VIP promote initiation of electrophysiological activity in
      differentiating embryonic stem cells.
AB  - Owing to their capacity to differentiate in vitro into various types of neuronal
      cells, embryonic stem (ES) cells represent a suitable model for studying the
      first steps of neuronal differentiation and cerebral development. Since pituitary
      adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal
      polypeptide (VIP) are known to control maturation of the nervous system, we have
      investigated the possible effects of these two neuropeptides on the
      differentiation of ES cells. Reverse transcription polymerase chain reaction (RT
      PCR) analysis revealed that mouse ES cells express PAC1 and VPAC2 receptors.
      Electrophysiological recordings demonstrated that PACAP and VIP facilitate the
      emission of currents, suggesting that these peptides can initiate the genesis of
      an electrophysiological activity in differentiating ES cells.

PMID- 16888164
TI  - Vasoactive intestinal peptide generates CD4+CD25+ regulatory T cells in vivo:
      therapeutic applications in autoimmunity and transplantation.
AB  - CD4+ CD25+ regulatory T cells (Treg) control the immune response to a variety of
      antigens, including self-antigens, and several models support the idea of the
      peripheral generation of CD4+ CD25+ Treg from CD4+ CD25- T cells. However, little
      is known about the endogenous factors and mechanisms controlling the peripheral
      expansion of CD4+ CD25+ Treg. We have found that the immunosuppressive
      neuropeptide vasoactive intestinal peptide (VIP) induces functional Treg in vivo.
      The administration of VIP together with specific antigen to TCR-transgenic mice
      results in the expansion of the CD4+ CD25+, Foxp-3/neuropilin 1-expressing T
      cells, which inhibit responder T cell proliferation through direct cellular
      contact. The VIP-generated CD4+ CD25+ Treg transfer suppression, inhibiting
      delayed-type hypersensitivity in the hosts, prevent graft-versus-host disease in
      irradiated host reconstituted with allogeneic bone marrow, and significantly
      ameliorate the clinical score in the collagen-induced arthritis model for
      rheumatoid arthritis and in the experimental autoimmune encephalomyelitis model
      for multiple sclerosis.

PMID- 16888165
TI  - Endogenous release of secretin from the hypothalamus.
AB  - Previous studies demonstrated that secretin could be released from the
      cerebellum, where it exerts a facilitatory action on the GABAergic inputs into
      the Purkinje neurons. In the present article, we provide evidence of the
      endogenous release of secretin in the hypothalamus and the mechanisms underlying
      this release. Incubation of the hypothalamic explants with KCl induces the
      release of secretin to 4.35 +/- 0.45-fold of the basal level. This K+-induced
      release was tetrodotoxin and cadmium sensitive, suggesting the involvement of
      voltage-gated sodium and calcium channels. The use of specific blockers further
      revealed the involvement of L-, N-, and P-type high voltage-activated (HVA)
      calcium channels. Results present in the current article provide further and more
      solid evidence of the role of secretin as a neuropeptide in the mammalian central
      nervous system.

PMID- 16888166
TI  - Expression of PACAP receptors in the frog brain during development.
AB  - This study describes the expression of PAC1 and VPAC1 receptor (PAC1-R and VPAC1
      R) mRNAs in the brain of frog (Rana esculenta) during development. PAC1-R mRNA
      was detected in the periventricular and subependymal layers of the thalamus and
      epithalamus and in the ependymal layer of the mesencephalon and rhombencephalon
      (stage 20), in the amygdala, in the habenular complex, in the periventricular
      nucleus of the hypothalamus, and in the ventral cerebellum (stage 30). VPAC1-R
      mRNA expression was observed only at stage 20, in the floor of the hypothalamus.
      These results suggest that, in amphibians, pituitary adenylate cyclase-activating
      polypeptide (PACAP) may play a role in brain development.

PMID- 16888168
TI  - VPAC2 receptor activation mediates VIP enhancement of population spikes in the
      CA1 area of the hippocampus.
AB  - The receptors mediating vasoactive intestinal polypeptide (VIP) enhancement of
      synaptic transmission to pyramidal cell bodies were investigated. RO 25-1553
      (VPAC2agonist) mimicked the excitatory effect of VIP on population spike (PS)
      amplitude. [K15, R16, L27] VIP (1-7)/GRF (8-27) (VPAC1 agonist) caused only a
      small increase in PS amplitude. The effect of VPAC2 agonist (but not of the VPAC1
      agonist) persisted upon blockade of GABAergic transmission and was strongly
      attenuated upon inhibition of PKA. In conclusion, VPAC2 receptor activation
      mediates VIP enhancement of PS amplitude in the hippocampus essentially through a
      PKA-dependent mechanism.

PMID- 16888167
TI  - The human VPAC1 receptor: identification of the N-terminal ectodomain as a major
      VIP-binding site by photoaffinity labeling and 3D modeling.
AB  - The human VPAC1 receptor for VIP and PACAP is a class II Gprotein-coupled
      receptor (GPCR). The N-terminal ectodomain of the VPAC1 receptor plays a crucial
      role in VIP binding. Photoaffinity experiments clearly indicated that the 6-28
      part of VIP physically interacts with the N-terminal ectodomain. Construction of
      a 3D model of the N-terminal ectodomain of VPAC1 receptor based on the NMR
      structure of the mouse CRF receptor 2 indicated the presence of short consensus
      repeat/Sushi domain. Docking of VIP in the N-terminal ectodomain structural model
      was performed taking into account the severe constraints provided by
      photoaffinity. A VIP-binding site was identified on the side of the structured
      core of the N-terminal ectodomain of the receptor.

PMID- 16888169
TI  - Expression and GTP sensitivity of peptide histidine isoleucine high-affinity
      binding sites in rat.
AB  - High-affinity-binding sites for the vasoactive intestinal peptide (VIP) analogs
      peptide histidine/isoleucine-amide (PHI)/carboxyterminal methionine instead of
      isoleucine (PHM) are expressed in numerous tissues in the body but the nature of
      their receptors remains to be elucidated. The data presented indicate that PHI
      discriminated a high-affinity guanosine 5'-triphosphate (GTP)-insensitive-binding
      subtype that represented the totality of the PHI-binding sites in newborn rat
      tissues but was differentially expressed in adult animals. The GTP-insensitive
      PHI/PHM-binding sites were also observed in CHO cells over expressing the VPAC2
      but not the VPAC1 VIP receptor.

PMID- 16888170
TI  - PACAP, VIP, and PHI: effects on AC-, PLC-, and PLD-driven signaling systems in
      the primary glial cell cultures.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP), vasoactive intestinal
      peptide (VIP), and peptide histidine-isoleucine (PHI) are members of a
      superfamily of structurally related peptides widely distributed in the body and
      displaying pleiotropic biological activities. All these peptides are known to act
      via common receptors-VPAC1 and VPAC2. In addition, the effects of PACAP are
      mediated through its specific receptor named PAC1. The main signal transduction
      pathway of the mentioned receptors is adenylyl cyclase (AC)-->cAMP system. PACAP
      and VIP may also signal through receptor-linked phospholipase C (PLC)-->IP3/DAG-
      >PKC and phospholipase D (PLD)-->phosphatidic acid (PA) pathways. In the present
      article, we have studied the effects of PACAP, VIP, and PHI (0.001-5000 nM) on
      the AC-, PLC-, and PLD-driven signaling pathways in rat primary glial cell
      (astrocytes) cultures. All tested peptides dose-dependently and strongly
      stimulated cyclic adenosine 3',5'-monophosphate (cAMP) production in this
      experimental model, displaying the following rank order of potency: PACAP >> VIP
      > or = PHI. Their effects on PLC-IP3/DAG were weaker, while only PACAP and VIP
      (0.1-5 microM) significantly stimulated PLD activity. The obtained results showed
      that rat cerebral cortex-derived astrocytes are responsive to PACAP, VIP and
      PHI/PHM and possess PAC1 and likely VPAC-type receptors linked to activation of
      AC-cAMP-, PLC-IP3/DAG-, and PLD-PA signaling systems.

PMID- 16888172
TI  - Vasoactive intestinal peptide: the dendritic cell --> regulatory T cell axis.
AB  - Tolerogenic dendritic cells (tDCs) play an important role in maintaining
      peripheral tolerance through the induction/activation of regulatory T cells
      (Treg). Endogenous factors contribute to the functional development of tDCs. In
      this article, we present evidence that two known immunosuppressive neuropeptides,
      the vasoactive intestinal peptide (VIP) and the pituitary adenylate cyclase
      activating polypeptide (PACAP), contribute to the development of bone marrow
      derived tDCs. The VIP/PACAP-generated DCs are CD11clowCD45RBhigh, do not
      upregulate CD80, CD86, and CD40 following lipopolysaccharide (LPS) stimulation,
      and secrete high amounts of IL-10. The VIP/PACAP-generated DCs induce functional
      Treg in vitro and in vivo. VIP/DCs induce antigen-specific tolerance in vivo,
      suppress delayed-type hypersensitivity (DTH), and T cells from VIP/DC-inoculated
      mice transfer the suppression to naive hosts. The effect of VIP/PACAP on the DC
      Treg axis represents an additional mechanism for their general anti-inflammatory
      role, particularly in anatomical sites that exhibit immune deviation or
      privilege.

PMID- 16888171
TI  - Vasoactive intestinal polypeptide induces regulatory dendritic cells that prevent
      acute graft versus host disease and leukemia relapse after bone marrow
      transplantation.
AB  - Acute graft-versus-host disease (GVHD) is a major cause of morbidity and
      mortality in patients undergoing allogeneic bone marrow transplantation (BMT) for
      the treatment of leukemia and other immunogenetic disorders. The use of
      tolerogenic dendritic cells (DCs) with potent immunoregulatory properties by
      inducing the generation/activation of regulatory T cells (Tr) for the treatment
      of acute GVHD following allogeneic BMT has been recently established. Here we
      report the use of the known immunosuppressive neuropeptide, vasoactive intestinal
      polypeptide (VIP), as a new approach to inducing tolerogenic DCs with the
      capacity to prevent acute GVHD. DCs differentiated with VIP impair allogeneic
      haplotype-specific responses of donor CD4+ T cells in transplanted mice by
      inducing the generation of Tr in the graft. Importantly, VIP-induced tolerogenic
      DCs did not abrogate the graft versus leukemia response, probably because they do
      not abrogate cytotoxicity of transplanted T cells against the leukemic cells.
      Therefore, the inclusion of VIP-induced tolerogenic DC in future therapeutic
      regimens may facilitate the successful transplantation from mismatched donors,
      reducing the deleterious consequences of acute GVHD, extending the applicability
      of BMT.

PMID- 16888173
TI  - VIP and PACAP receptor pharmacology: a comparison of intracellular signaling
      pathways.
AB  - VIP/PACAP receptor activation stimulates the production of [cAMP]i and [Ca2+]i by
      coupling to independent G-protein subunits, although agonist potencies for the
      different transduction pathways appear to differ. Using CHO-K1 cells stably
      expressing the human VIP/PACAP receptors (hVPAC1R, hVPAC2R, and hPAC1R),
      functional assays ([cAMP]i and [Ca2+]i) were established and the receptor
      pharmacology was characterized with five peptide agonists (VIP, PACAP-27, PACAP
      38, [Ala(11,22,28)]VIP, and R3P65). The rank order of potency (ROP) was
      consistent between assays for the individual receptor subtypes, however, higher
      agonist concentrations (approximately 100-fold) were required for stimulating
      [Ca2+]i when compared to [cAMP]i.

PMID- 16888174
TI  - Molecular approximation between residue 10 of secretin and its receptor
      demonstrated by photoaffinity labeling.
AB  - Using photoaffinity labeling, we have previously explored the molecular
      approximations between multiple positions of secretin and its receptor.
      Interestingly, the amino-terminal secretin probe incorporating a photolabile
      residue in position 1 labels the top of the sixth transmembrane domain of the
      receptor, whereas other probes with photolabile residue in positions 6, 12, 13,
      14, 18, 22, and 26 all label the long amino-terminal domain of the secretin
      receptor. Recently, we have developed a secretin probe that incorporated a
      radioiodinatable photolabile p-(4-hydroxybenzoyl)phenylalanine in position 10 and
      demonstrated that it efficiently labeled the secretin receptor in a saturable and
      specific manner. In this work, we attempted to further map its domain of labeling
      by cyanogen bromide (CNBr) cleavage of the wild-type and mutant receptors.
      Surprisingly, this position 10 probe labeled the top of the sixth transmembrane
      domain of the receptor, a domain labeled by the position 1 probe. These data
      provide an important constraint for modeling the agonist-bound G protein-coupled
      secretin receptor and should add substantially to our current understanding of
      the molecular basis of ligand binding of this important receptor.

PMID- 16888175
TI  - Use of photoaffinity labeling to understand the molecular basis of ligand binding
      to the secretin receptor.
AB  - The secretin receptor was the first member of the Class B family of G protein
      coupled receptors that was identified in 1991, 89 years after secretin action was
      first recognized. That report resulted in the introduction of the term hormone
      and in the birth of the field of endocrinology. The secretin receptor has become
      prototypic of this receptor family, binding a moderately long linear peptide with
      a diffuse pharmacophoric domain. Here, we provide a detailed account of the
      contributions of photoaffinity labeling to establish the molecular basis of
      natural ligand binding to this receptor, as well as to provide insights into
      possible mechanisms for receptor activation and initiation of signaling. Each of
      the themes discussed are also relevant to other members of this physiologically
      and pharmacologically important receptor family.

PMID- 16888176
TI  - PACAP and ceramides exert opposite effects on migration, neurite outgrowth, and
      cytoskeleton remodeling.
AB  - During brain development, cells that fail to reach their final destination or to
      establish proper connections are eliminated. It has been shown that the
      proinflammatory cytokine second messenger ceramides and the neuropeptide
      pituitary adenylate cyclase-activating polypeptide (PACAP) play pivotal roles in
      the histogenesis of the cerebellum. However, little is known regarding the
      effects of these two factors on cerebellar granule cell migration. We have found
      that PACAP prevents the effects of C2-ceramide on granule cell motility and
      neurite outgrowth. These actions are attributable to opposite effects on actin
      distribution, tubulin polymerization, and Tau phosphorylation. These data suggest
      that PACAP and factors inducing ceramide production may control granule cell
      migration during cerebellar development.

PMID- 16888177
TI  - The effects of PACAP and VIP on the in vitro melatonin secretion from the
      embryonic chicken pineal gland.
AB  - The effects of in vitro VIP administration and those of in ovo pretreatment with
      PACAP antagonist (PACAP6-38) on the development of the embryonic melatonin (MT)
      secretion were investigated. With dynamic in vitro bioassay we showed that (1)
      the development of the circadian MT secretion seems to be unaffected by VIP
      administrations or by PACAP6-38 pretreatments; (2) exposure of the embryonic
      chicken pineal gland to VIP induces transitory increase in MT secretion at or
      before the 14th embryonic day in vitro.

PMID- 16888179
TI  - C-type natriuretic peptide is specifically augmented by pituitary adenylate
      cyclase-activating polypeptide in rat astrocytes.
AB  - In rat-cultured astrocytes, pituitary adenylate cyclase-activating polypeptide
      (PACAP) activates gene expression and secretion of C-type natriuretic peptide
      (CNP) in a dose- and time-dependent manner. These results suggest that PACAP
      might be involved in the regulation of CNP biosynthesis in astrocytes.

PMID- 16888178
TI  - VIP prevents experimental multiple sclerosis by downregulating both inflammatory
      and autoimmune components of the disease.
AB  - Multiple sclerosis (MS) is a disabling inflammatory, autoimmune demyelinating
      disease of the central nervous system (CNS). Despite intensive investigation, the
      mechanisms of disease pathogenesis remain unclear, and curative therapies are
      unavailable for MS. The current study describes a new possible strategy for the
      treatment of MS, based on the administration of the vasoactive intestinal peptide
      (VIP). Treatment with VIP significantly reduced incidence and severity of
      experimental autoimmune encephalomyelitis (EAE), an MS-related rodent model. VIP
      suppressed EAE neuropathology by reducing CNS inflammation and by selective
      blocking encephalitogenic T-cell reactivity, emerging as an attractive candidate
      for the treatment of human MS.

PMID- 16888180
TI  - Aromatase gene expression and regulation in the female rat pituitary.
AB  - Aromatase cytochrome P450, the key enzyme of estrogen biosynthesis from
      androgens, is encoded by CYP19. Its structure shows some peculiarities: exons II
      to X encode the protein, while multiple alternative exons I encode unique 5'
      untranslated regions of the aromatase mRNA transcripts. Immunohistochemistry
      studies in the rat have shown that pituitary aromatase expression is sex
      dependent and varies across the estrous cycle, suggesting that estrogens might be
      involved in the regulation of aromatase activity and might act locally as a
      paracrine or autocrine factor in the pituitary. In the present study, we used RT
      PCR to characterize aromatase transcripts and real-time PCR to quantify the
      expression of the total aromatase mRNA at the different stages of the estrous
      cycle and from an ovariectomy and estradiol replacement model. We identified the
      two previously described aromatase transcripts with a specific 5'untranslated
      region of the brain 1f and the gonadal PII transcripts. Total aromatase mRNA
      expression in the pituitary varied significantly during the estrous cycle, with
      the highest level occurring on the day of metestrus. After ovariectomy, we
      observed an increase of aromatase mRNA levels, and this effect was completely
      prevented by estradiol administration. These results suggest that pituitary
      aromatase mRNA expression is downregulated by estrogens.

PMID- 16888181
TI  - Modulation of pituitary adenylate cyclase-activating polypeptide (PACAP)
      expression in explant-cultured guinea pig cardiac neurons.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) expression was
      quantified in explant-cultured guinea pig cardiac ganglia neurons. In explant
      culture, both the percentage of PACAP-immunoreactive neurons and pro-PACAP
      transcript levels increased significantly. Treatment with neurturin or glial
      derived neurotrophic factor significantly suppressed the percentage of PACAP-IR
      neurons, but not pro-PACAP transcript levels.

PMID- 16888182
TI  - VIP: an agent with license to kill infective parasites.
AB  - Antimicrobial peptides are small, cationic, and amphipathic peptides of variable
      length, sequence, and structure. They are effector molecules of innate immunity
      with microbicidal and both pro- or anti-inflammatory activities. Vasoactive
      intestinal polypeptide (VIP) and the structurally related pituitary adenylate
      cyclase-activating polypeptide (PACAP) are well-known immunomodulators. On the
      basis of their cationic and amphipathic structures, resembling antimicrobial
      peptides, we propose that their immune role could also include a direct lethal
      effect against pathogens. We thus investigated the potential antiparasitic
      activities of VIP and PACAP against the African trypanosome Trypanosoma brucei
      (T. brucei). Both peptides killed the bloodstream (infective) form but not the
      insect (noninfective) form of the parasite. VIP and PACAP caused complete
      destruction of the parasite integrity through a mechanism involving their entry
      and accumulation into the cytosol. These results provide the basis for further
      studies of these and other structurally related peptides as alternative
      treatments for parasitic diseases mainly with associated drug resistances.

PMID- 16888183
TI  - PACAP stimulates the release of the secretogranin II-derived peptide EM66 from
      chromaffin cells.
AB  - The aim of the present article was to examine the effect of PACAP on the release
      of the SgII-derived peptide EM66 from primary cultures of bovine chromaffin
      cells. PACAP dose dependently stimulated EM66 release from cultured chromaffin
      cells. A significant response was observed after 6 h of treatment with PACAP and
      increased to reach a 3.6-fold stimulation at 72 h. The stimulatory effect of
      PACAP was mediated through multiple signaling pathways, including calcium influx
      through L-type channels, PKA, PKC, and MAP-kinase cascades, to regulate EM66
      release from chromaffin cells. These data suggest that EM66 may act downstream of
      the trans-synaptic stimulation of the adrenal medulla by neurocrine factors.

PMID- 16888184
TI  - New nonradioactive technique for vasoactive intestinal peptide-receptor-ligand
      binding studies.
AB  - We describe fluorescent-labeled peptide (FLP) studies on living cells. The new
      technique is nonradioactive and it allows monitoring of the binding and
      internalization of Vasoactive Intestinal Peptide (VIP) in VIP receptor-expressing
      cells. The technique is easy to perform and the observed reaction is peptide
      sequence specific.

PMID- 16888185
TI  - Calcium influx through channels other than voltage-dependent calcium channels is
      critical to the pituitary adenylate cyclase-activating polypeptide-induced
      increase in excitability in guinea pig cardiac neurons.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) effects on
      intracellular calcium ([Ca2+]i) and excitability have been studied in adult
      guinea pig intracardiac neurons. PACAP increased excitability, but did not elicit
      Ca2+ release from intracellular stores. Exposure to a Ca2+-deficient solution did
      not deplete [Ca2+]i stores but did eliminate the PACAP-induced increase in
      excitability. We postulate that Ca2+ influx is required for the PACAP-induced
      increase in excitability.

PMID- 16888186
TI  - Mechanisms and modulation of pituitary adenylate cyclase-activating protein
      induced calcium mobilization in human neutrophils.
AB  - The neuropeptide pituitary adenylate cyclase-activating protein (PACAP) acts via
      the G protein-coupled receptor vasoactive intestinal peptide (VIP)/PACAP receptor
      1 to induce phospholipase C (PLC)/calcium and mitogen-activated protein kinase
      (MAPK)-dependent proinflammatory activities in human polymorphonuclear
      neutrophils (PMNs). In this article, we evaluate other mechanisms that regulate
      PACAP-evoked calcium transients, the nature of the calcium sources, and the role
      of calcium in proinflammatory activities. Reduction in the activity of PMNs to
      respond to PACAP was observed after cell exposure to inhibitors of the
      cAMP/protein kinase A (PKA), protein kinase C (PKC), and PI3K pathways, to
      pertussis toxin (PTX), genistein, and after chelation of intracellular calcium or
      after extracellular calcium depletion. Mobilization of intracellular calcium
      stores was based on the fact that PACAP-associated calcium transient was
      decreased after exposure to (a) thapsigargin (Tg), (b) xestospongin C (XeC), and
      (c) the protonophore carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone;
      inhibition of calcium increase by calcium channel blockers, by nifedipine and
      verapamil, indicated that PACAP was also acting on calcium influx. Such
      mobilization was not dependent on a functional actin cytoskeleton. Homologous
      desensitization with nanomoles of PACAP concentration and heterologous receptors
      desensibilization by G protein-coupled receptor agonists were observed.
      Intracellular calcium depletion modulated PACAP-associated ERK but not p38
      phosphorylation; in contrast, extracellular calcium depletion modulated PACAP
      associated p38 but not ERK phosphorylation. In PACAP-treated PMNs, reactive
      oxygen species production and CD11b membrane upregulation in contrast to
      lactoferrin release were dependent on both intra- and extracellular calcium,
      whereas matrix metalloproteinase-9 release was unaffected by extracellular
      calcium depletion. These data indicate that both extracellular and intracellular
      calcium play key roles in PACAP proinflammatory activities.

PMID- 16888187
TI  - PACAP enhances mouse urinary bladder contractility and is upregulated in
      micturition reflex pathways after cystitis.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) elicits a transient
      contraction, sustained increase in the amplitude of spontaneous phasic
      contractions, and significantly increases the amplitude of nerve-mediated
      contractions in mouse urinary bladder smooth muscle (UBSM) strips. PACAP
      immunoreactivity (IR) is increased in micturition reflex pathways following
      cystitis. PACAP may contribute to altered sensation and bladder overactivity in
      the chronic bladder inflammatory syndrome, interstitial cystitis.

PMID- 16888188
TI  - Protective role for plasmid DNA-mediated VIP gene transfer in non-obese diabetic
      mice.
AB  - Studies focused on the development of diabetes in NOD mice-a model for human type
      1 diabetes-have revealed that an autoimmune inflammatory process is produced by
      the effect of Th1 cells and their secreted cytokines. DNA vaccination has been
      shown to be an effective method for modulating immunity in viral infections and
      experimental autoimmune diseases, including diabetes. VIP's immunomodulatory
      properties are partly mediated by skewing the pattern of cytokines from a
      proinflammatory response to an anti-inflammatory response. Using gene delivery to
      express VIP, we interfered in the immune process leading to diabetes in prone,
      cyclophosphamide-treated NOD mice. Our results extend the role of VIP in the
      control of immunoregulatory networks and open new perspectives for
      immunointervention through VIP-based gene therapy.

PMID- 16888189
TI  - Inhibition of self-renewal and induction of neural differentiation by PACAP in
      neural progenitor cells.
AB  - Several lines of evidence have suggested roles for pituitary adenylate cyclase
      activating polypeptide (PACAP) in the developing nervous system. Previously, we
      showed that mRNA for PACAP, vasoactive intestinal peptide (VIP), and their three
      receptor subtypes, is differentially expressed in embryonic stem (ES) cells, ES
      cell-derived, neural stem cell-enriched cultures, and differentiated neurons, by
      using the five steps of the in vitro neuronal culture model of ES cell
      differentiation. Here, we examined the effects of PACAP on self-renewal and cell
      lineage determination of neural progenitor/stem cells. PACAP inhibited the basic
      fibroblast growth factor-induced proliferation (self-renewal), as assessed by
      neurosphere formation. PACAP increased microtubule-associated protein 2-positive
      neurons without affecting the number of cells positive for the neural stem cell
      marker nestin, astrocyte marker glial fibrillary acidic protein, and
      oligodendrocyte marker CNPase. These results suggest that PACAP inhibits self
      renewal but, instead, induces early neuronal differentiation of neural progenitor
      cells.

PMID- 16888190
TI  - Presence of PACAP and VIP in embryonic chicken brain.
AB  - The aim of the present article was to investigate the occurrence and temporary
      changes of pituitary adenylate cyclase-activating polypeptide (PACAP)-38 and
      vasoactive intestinal peptide (VIP) in various brain areas of chicken embryos by
      means of radioimmunoassay. The highest concentrations of PACAP-38 were measured
      in the brain stem followed by the hypothalamus, cerebellum, and telencephalon.
      PACAP-38 levels were significantly higher than those of VIP in all examined brain
      areas. The levels of both PACAP-38 and VIP showed a tendency to decrease until
      hatching during embryonic development of the chicken.

PMID- 16888191
TI  - Short-term fasting differentially alters PACAP and VIP levels in the brains of
      rat and chicken.
AB  - The present article investigated the levels of pituitary adenylate cyclase
      activating polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP) in the
      brains of rats and chickens 12, 36, and 84 h after starvation. PACAP levels
      increased in both species, 12 h after food deprivation in rats, and with a 24-h
      delay in chickens. VIP levels showed a more complex pattern: a gradual increase
      in the hypothalamus and telencephalon, and a significant decrease in the brain
      stem of rats. In chickens, a decrease was observed in every brain area after 36 h
      of starvation. These data show that PACAP and VIP are differentially regulated
      and are involved in the regulatory processes under a food-restricted regimen, and
      are differentially altered in nocturnal and diurnal species.

PMID- 16888192
TI  - VIP decreases TLR4 expression induced by LPS and TNF-alpha treatment in human
      synovial fibroblasts.
AB  - It has been demonstrated that VIP produces beneficial effects both in a murine
      model of rheumatoid arthritis and in human rheumatoid synovial fibroblasts
      through the modulation of proinflammatory mediators. Toll-like receptors (TLRs)
      play a key role in the immediate recognition of microbial surface components by
      immune cells prior to the development of adaptative microbe-specific immune
      responses. In this study, we demonstrate that VIP decreases lipopolysaccharide
      (LPS) and TNF-alpha-induced expression of TLR4 and its correlation with the
      production of CCL2 and CXCL8 chemokines in human synovial fibroblasts from
      patients with rheumatoid arthritis and osteoarthritis. Our results add a new step
      for the use of VIP, as a promising candidate, for the treatment of rheumatoid
      arthritis.

PMID- 16888193
TI  - Effects of systemic PACAP treatment in monosodium glutamate-induced behavioral
      changes and retinal degeneration.
AB  - The present article investigated effects of systemic pituitary adenylate cyclase
      activating polypeptide (PACAP) treatment in monosodium glutamate (MSG)-induced
      retinal degeneration and neurobehavioral alterations in neonatal rats. It was
      found that the dose of PACAP that effectively enhances neurobehavioral
      development in normal rats was able to counteract the retarding effect of MSG on
      righting, forelimb placing, and grasp reflexes and caused a significant
      amelioration of the righting and gait reflex performance and motor coordination
      at 2 weeks of age. In the retina, significant amelioration of neuronal loss in
      the inner retinal layers was achieved, but it was much less than that observed by
      local administration.

PMID- 16888194
TI  - Localization of small heterodimer partner (SHP) and secretin in mouse duodenal
      cells.
AB  - Previous studies have demonstrated the transcriptional repressive property of the
      atypical nuclear receptor, small heterodimer partner (SHP), on NeuroD. NeuroD is
      a basic helix-loop-helix transcription factor that has also been shown to be
      important in modulating secretin gene expression. The present study revealed the
      activation of the human secretin core promotor by overexpressing NeuroD, and the
      localization of SHP and secretin-producing cells in mouse duodenal epithelium by
      immunohistochemical stainings. These results indicated that SHP and secretin are
      potentially co-expressed and lead us to propose a novel regulatory pathway, in
      which SHP represses NeuroD's positive regulatory activity on secretin gene.

PMID- 16888195
TI  - Differential mechanisms for PACAP and GnRH cAMP induction contribute to cross
      talk between both hormones in the gonadotrope LbetaT2 cell line.
AB  - The effects and respective influence of pituitary adenylate cyclase-activating
      polypeptide (PACAP) and gonadotropin-releasing hormone (GnRH) on cyclic AMP
      (cAMP) production in pituitary gonadotropes were analyzed using the LbetaT2 cell
      line. Both hormones induced cAMP with, however, different intensity and time
      course. In addition, the GnRH effect was markedly reduced by PKC inhibitors.
      Despite its positive coupling to cAMP pathway, GnRH counteracted PACAP induction
      of cAMP and this effect was mimicked by the PKC activator phorbol 12-myristate 13
      acetate (PMA). The data reveal major differences in the mechanisms by which PACAP
      and GnRH activate cAMP/PKA pathway in LbetaT2 cells and suggest that PKC
      activation serves GnRH not only to increase cAMP but also to counteract the PACAP
      stimulation of this signaling pathway.

PMID- 16888196
TI  - Identification of proteins regulated by PACAP in PC12 cells by 2D gel
      electrophoresis coupled to mass spectrometry.
AB  - The rat pheochromocytoma PC12 cell line has been widely used as a model to study
      neuronal differentiation. In particular, after serum depletion, PC12 cells stop
      to proliferate and undergo apoptosis. Under such conditions, treatment with
      pituitary adenylate cyclase-activating polypeptide (PACAP) promotes cell survival
      and induces neurite outgrowth. The identification of the proteins regulated by
      PACAP in PC12 cells under apoptotic conditions should provide valuable
      information concerning the mechanisms controlling neuronal cell survival and
      differentiation. To this aim, PC12 cells cultured in serum-free medium were
      treated with PACAP (10(-7) M), proteins were extracted, separated by two
      dimensional gel electrophoresis (2-DE), and identified by MALDI-ToF mass
      spectrometry. The comparison between 16 2-DE maps led to the characterization of
      110 proteins regulated by PACAP among which 22 have been identified by automatic
      query of the Mascot, Aldente, and Profound servers with the ProGeR-CDD database.
      Seventy-six percent of these proteins, including the p17 subunit of caspase-3,
      the heat shock protein hsp60, and the GTPase ran were found to be repressed
      whereas the others notably hsp27, tubulin beta-5, and calmodulin were
      overexpressed. Investigation of the putative functions indicated that some of the
      proteins regulated by PACAP and identified in the present article could control
      cell survival or differentiation.

PMID- 16888197
TI  - Identification of repressor element 1 in secretin/PACAP/VIP genes.
AB  - Repressor element 1 (RE-1) is a negative, cis-acting regulatory element that
      interacts with the transcription factor RE-1-silencing transcription factor
      (REST). REST represses gene expression by two repressor domains that recruit
      other factors including mSin3 and CoREST. RE-1 has been identified in an
      increasing number of neuronal-specific genes, and recently, functional REST sites
      have also been discovered in VIP and PACAP genes. In the present article, we
      demonstrated for the first time that RE-1 sites are present in the 5' flanking
      regions of several secretin/PACAP/VIP genes by in silico analysis. This
      observation suggests that RE-1/REST is a common negative regulatory pathway of
      this peptide family.

PMID- 16888198
TI  - Retinoic acid-induced human secretin gene expression in neuronal cells is
      mediated by cyclin-dependent kinase 1.
AB  - Previously, we found that secretin transcript levels were induced by all-trans
      retinoic acid (RA) in a neuroblastoma cell model, SH-SY5Y. In this article, this
      RA-dependent upregulation process was further investigated. In the cyclin
      dependent kinase 1 (Cdk1) inhibitor-treated cells, the RA-dependent induction of
      secretin gene expression was inhibited. Together with our previous works, we
      propose here that the RA responsiveness of the secretin promotor is mediated by
      two different pathways. The first pathway is by changing the expression levels of
      NFI-C and Sp proteins while the second pathway is by modifying the
      phosphorylation status of both NFI-C and Sp proteins via Cdk1.

PMID- 16888200
TI  - PAC1 receptor: emerging target for septic shock therapy.
AB  - Septic shock is a systemic response to severe bacterial infections, generally
      caused by Gram-negative bacterial endotoxins, with multiple manifestations such
      as hypotension, tissue injury, disseminated intravascular coagulation, and multi
      organ failure. All these effects, are induced by the generation of pro
      inflammatory and vasodilator mediators, cell adhesion molecules, coagulation
      factors, and acute-phase proteins. Vasoactive intestinal polypeptide (VIP) and
      pituitary adenylate cyclase-activating polypeptide (PACAP) are two immunopeptides
      with anti-inflammatory properties exerted through type 1 and 2 VIP receptors
      (VPAC1 and VPAC2, respectively), and PACAP receptor (PAC1). The present results
      recapitulate the protective role of PAC1 in an experimental model of lethal
      endotoxemia using a knockout for the PAC1 receptor. Our results demonstrate that
      VIP and PACAP decrease lipopolysaccharide (LPS)-induced interleukin-6 (IL-6)
      production, neutrophil infiltration and intercellular adhesion molecule-1 (ICAM
      1), vascular cell adhesion molecule-1 (VCAM-1), and fibrinogen expression through
      PAC1 receptor, providing an advantage to design more specific drugs complementing
      standard intensive care therapy in septic shock.

PMID- 16888201
TI  - PACAP stimulates biosynthesis and release of endozepines from rat astrocytes.
AB  - Astrocytes synthesize and release endozepines, a family of neuropeptides related
      to diazepam-binding inhibitor (DBI). Astroglial cells also express the receptors
      of pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive
      intestinal polypeptide (VIP). In the present article, we show that PACAP dose
      dependently increases DBI gene expression and stimulates endozepine release
      through activation of PAC1-R. PACAP increases cAMP formation, enhances
      polyphosphoinositide turnover, and evokes calcium mobilization from intracellular
      Ca2+ pools. The effect of PACAP on endozepine release is mediated through the
      adenylyl cyclase/PKA pathway while the downregulation of astrocyte response to
      PACAP can be ascribed to activation of the PLC/PKC pathway.

PMID- 16888202
TI  - Effects of pituitary adenylate cyclase-activating polypeptide and vasoactive
      intestinal polypeptide on food intake and locomotor activity in the goldfish,
      Carassius auratus.
AB  - We investigated the effects of intracerebroventricular (ICV) and intraperitoneal
      (IP) administration of pituitary adenylate cyclase-activating polypeptide (PACAP)
      and vasoactive intestinal polypeptide (VIP) on food intake in the goldfish,
      Carassius auratus. Cumulative food intake was significantly decreased by ICV
      injection of PACAP or VIP. Similarly, IP administration of PACAP or VIP induced a
      significant decrease in food intake. ICV injection of PACAP or VIP also induced a
      significant decrease in locomotor activity. These results suggest that PACAP and
      VIP may be involved in the regulation of feeding in goldfish.

PMID- 16888199
TI  - Neuroendocrine tumors express PAC1 receptors.
AB  - Neuroendocrine tumors (NETs) of the gastrointestinal tract can be grossly divided
      into two general types: carcinoid and pancreatic endocrine tumors. The former
      develop in the luminal intestine whereas the latter occur within the pancreas. To
      ascertain whether pituitary adenylate cyclase-activating polypeptide (PACAP) has
      a biological effect on the regulation of secretion or growth, we studied the well
      established NET cell line, BON. BON cells have been shown previously to contain
      chromogranin A, neurotensin, and serotonin. In response to mechanical
      stimulation, BON cells have been demonstrated to release serotonin. The current
      article demonstrates that the high-affinity PAC1 receptor is expressed on the NET
      cell line BON. These results indicate that PACAP may regulate the biological
      release of peptides and serotonin from BON cells and that, like in solid tumors,
      PACAP could potentially stimulate the growth of BON cells.

PMID- 16888203
TI  - Functional splice variants of the type II G protein-coupled receptor (VPAC2) for
      vasoactive intestinal peptide in mouse and human lymphocytes.
AB  - A PCR-based search for splice variants of the VPAC2 G protein-coupled receptor
      for vasoactive intestinal peptide (VIP) revealed: (a) a short-deletion variant in
      mouse lymphocytes termed VPAC2de367-380, that lacks 14 amino acids in the seventh
      transmembrane domain, and (b) a long-deletion variant in human lymphocytes termed
      VPAC2de325-438(i325-334), that lacks 114 amino acids beginning with the carboxyl
      terminal end of the third cytoplasmic loop and has 10 new carboxy-terminal amino
      acids. VPAC2de367-380 binds VIP normally, but shows reduced VIP-evoked signaling
      and effects on immune functions, whereas VPAC2de325-438(i325-334) shows reduced
      binding affinity for VIP and a complex pattern of functional differences. These
      splice variants may modify the immunoregulatory contributions of the VIP-VPAC2
      axis.

PMID- 16888204
TI  - Comparative anatomy of PACAP-immunoreactive structures in the ventral nerve cord
      ganglia of lumbricid oligochaetes.
AB  - By means of a whole mount immunocytochemical approach, the distribution patterns
      of pituitary adenylate cyclase-activating polypeptide (PACAP)-27 and PACAP-38
      were identified in the ventral nerve cord (VNC) ganglia of the earthworms Eisenia
      fetida and Lumbricus terrestris. Each PACAP form appears to occur in a distinct
      neuron population. Positions of these populations, as well as numbers and sizes
      of the constituting neurons do not essentially differ between the two species.
      The data suggest that in Lumbricid Oligochaetes, PACAP-27 and PACAP-38 neuron
      populations may mediate distinct physiological processes.

PMID- 16888205
TI  - Involvement of the adenylyl cyclase/protein kinase A signaling pathway in the
      stimulatory effect of PACAP on frog adrenocortical cells.
AB  - We have previously shown that PACAP stimulates in vitro the secretion of
      corticosteroids by frog adrenal explants and that PACAP increases cAMP formation
      and cytosolic calcium concentration ('Ca2+'i) in adrenocortical cells. The aim of
      the present study was to investigate the involvement of cAMP and 'Ca2+'i in the
      stimulatory effect of PACAP on steroid production. Incubation of adrenal explants
      with PACAP resulted in a significant increase in total inositol phosphate
      formation. Administration of the protein kinase A inhibitor, H89, markedly
      reduced the stimulatory effect of PACAP on corticosterone and aldosterone
      secretion by perifused adrenal slices. In contrast, chelation of intracellular or
      extracellular calcium, or incubation with calcium channel blockers, had no effect
      on PACAP-evoked steroid secretion. Incubation of the cells with BAPTA or
      thapsigargin totally suppressed the stimulatory effect of PACAP on 'Ca2+'i. In
      contrast, suppression of extracellular calcium with EGTA or blockage of voltage
      dependent Ca2+ channels did not impair PACAP-induced Ca2+ response. These data
      indicate that, in frog adrenocortical cells, the stimulatory effect of PACAP on
      steroid secretion is mediated through activation of the cAMP/PKA pathway.
      Concurrently, PACAP causes calcium mobilization from IP(3)-dependent
      intracellular stores through activation of a phospholipase C, while the calcium
      response is not involved in the stimulatory effect of PACAP on corticosteroid
      secretion.

PMID- 16888207
TI  - PACAP and type I PACAP receptors in human prostate cancer tissue.
AB  - We characterized the expression and localization of pituitary adenylate cyclase
      activating polypeptide (PACAP) and its specific type I receptor variants in
      prostatic, hyperplastic, and carcinomatous tissue collected from patients
      undergoing prostate biopsy and surgery for benign prostatic hyperplasia (BPH) and
      prostate cancer (PCa). The immunohistochemical studies using an indirect
      immunoperoxidase technique evidenced positive immunostaining for PACAP in the
      cytoplasm of epithelial cells of hyperplastic and carcinomatous prostate
      specimens and in some scattered cells of the stroma. Type I PACAP receptors (PAC1
      R) in healthy and BPH tissues were localized in all epithelial cells lining the
      lumen of the acini and in some stromal cells, while in specimens from PCa the
      anti-PAC1 R antibody stained the apical portion of a large percentage of cells.
      Furthermore, our molecular studies provide evidence that several PAC1 R isoforms
      (null, SV1/SV2) are present in normal, hyperplastic, and neoplastic tissue, the
      null variant being the most intensely expressed in PCa. These observations
      provide additional evidence for a role of PACAP and PAC1 R in the events
      determining the outcome of PCa.

PMID- 16888208
TI  - Lack of trimethyltin (TMT)-induced elevation of plasma corticosterone in PACAP
      deficient mice.
AB  - Accumulating evidence implicates pituitary adenylate cyclase-activating
      polypeptide (PACAP) in a number of stress responses. By using PACAP-deficient
      mice, PACAP has been shown to have an in vivo role in the regulation of the
      sympathoadrenal axis, but a role in regulating the hypothalamo-pituitary-adrenal
      (HPA) axis has not been fully addressed. To elucidate the role of endogenous
      PACAP in HPA axis regulation during pathological conditions, mice lacking the
      Adcyap1 gene encoding the neuropeptide PACAP (Adcyap1-/-) were injected with
      trimethyltin (TMT), a neurotoxin known to induce neuronal damage and several
      systemic responses including elevated plasma corticosterone levels. In wild-type
      controls, TMT induced transient decreases in water and food intake, with a
      concomitant decrease in body weight; however, no significant changes were
      observed in Adcyap1-/- mice. Basal corticosterone levels were not significantly
      different between the mutant and wild-type mice. TMT induced a marked elevation
      of plasma corticosterone above basal levels in wild-type mice but no significant
      increase was seen in Adcyap1-/- mice. The present article suggests that PACAP is
      involved in the corticosterone release in some pathological conditions but not in
      the basal state.

PMID- 16888206
TI  - Breast cancer VPAC1 receptors.
AB  - VIP receptors were investigated in breast cancer biopsy specimens. Twenty biopsy
      specimens bound 125I-VIP with high affinity. Also, each of the 20 biopsy
      specimens had high amounts of VPAC1 receptor mRNA. MCF-7 cells have VPAC1
      receptors that bound the VIP chemotherapeutic conjugate, (Ala2,8,9,19,24,25,27
      Nle17, Lys28)VIP-L2-camptothecin, with high affinity. VIP chemotherapeutic
      conjugates may be useful agents to inhibit the growth of breast cancer.

PMID- 16888209
TI  - Expression of PACAP receptor mRNAs by neuropeptide Y neurons in the rat arcuate
      nucleus.
AB  - Neuropeptide Y (NPY) and pituitary adenylate cyclase-activating polypeptide
      (PACAP) exert opposite actions in energy homeostasis: NPY is a potent orexigenic
      peptide whereas PACAP reduces food intake. PAC1-R and VPAC2-R mRNAs are actively
      expressed in the arcuate nucleus of the hypothalamus which contains a prominent
      population of NPY neurons. By using a double-labeling in situ hybridization
      technique, we now show that a significant proportion of NPY neurons express PAC1
      R or VPAC2-R mRNA. This observation indicates that PACAP may regulate the
      activity of NPY neurons, suggesting that the inhibitory effect of PACAP on food
      intake may be mediated, at least in part, through modulation of NPY
      neurotransmission.

PMID- 16888210
TI  - Developmental pattern of VIP binding sites in the human hypothalamus.
AB  - We have studied the developmental patterns of vasoactive intestinal polypeptide
      (VIP) binding sites in the human hypothalamus. VIP recognition sites were widely
      distributed throughout the rostrocaudal extent of the hypothalamus. VIP binding
      was generally low in the fetal and neonatal periods and a tendency in increasing
      densities was observed during postnatal development. The age comparison of
      binding density indicates variations in several structures. Thus, the densities
      were higher in older infants in the preoptic area, lamina terminalis, and
      infundibular (IN) nucleus. These differences suggest the implication of VIP
      receptors in the development of this brain structure and the maintenance of its
      various functions.

PMID- 16888211
TI  - Changes in PACAP levels in the central nervous system after ovariectomy and
      castration.
AB  - The aim of the present article was to investigate the influence of gonadectomy on
      pituitary adenylate cyclase-activating polypeptide (PACAP) levels in different
      brain areas. In males, there seems to be an inverse relationship between
      gonadotropins and PACAP in the brain in the acute phase of castration: PACAP
      levels decreased in almost all brain areas examined within the first week after
      castration. In females, such pattern was observed in the hypothalamus, brain
      stem, and temporal cortex. In the pituitary, levels decreased only on the first
      day after ovariectomy, and later, as in the thalamus, increases were observed.
      Although the pattern of change showed gender differences, our results provide
      further evidence that levels of gonadotropins and possibly gonadotropin-releasing
      hormone influence PACAP levels and that PACAP is involved in the regulation of
      gonadal functions.

PMID- 16888213
TI  - The vasoactive intestinal peptide receptor turnover in pulmonary arteries
      indicates an important role for VIP in the rat lung circulation.
AB  - Vasoactive intestinal peptide (VIP) is a potent vasorelaxing peptide that plays a
      role in lung physiology and possibly in pulmonary hypertension. We investigated
      the turnover of the VIP receptors on rat pulmonary arteries ex vivo. There was
      evidence for a fast receptor turnover in pulmonary arteries, which underlines the
      important role of VIP for the regulation of pulmonary circulation and pulmonary
      pathology.

PMID- 16888212
TI  - Effects of pituitary adenylate cyclase-activating polypeptide, vasoactive
      intestinal polypeptide, and somatostatin on the release of thyrotropin from the
      bullfrog pituitary.
AB  - The recent development of a specific radioimmunoassay for amphibian (bullfrog,
      Rana catesbeiana) thyrotropin (TSH) has made it possible to study the effects of
      various neuropeptides on the release of TSH from the pituitary in vitro. Up to
      now, corticotropin-releasing factor of bullfrog origin has been shown to have a
      potent TSH-releasing activity, whereas gonadotropin-releasing hormone and TSH
      releasing hormone exhibit a moderate TSH-releasing effect on the adult, but not
      larval, pituitary. In the present study, the effects of pituitary adenylate
      cyclase-activating polypeptide (PACAP), vasoactive intestinal polypeptide (VIP),
      and somatostatin (SS) on the in vitro release of TSH from the bullfrog pituitary
      were investigated. Both frog (R. ridibunda) PACAP-38 and PACAP-27 caused a
      concentration-dependent stimulation of the release of TSH from dispersed
      pituitary cells during a 24-h culture. The PACAP-38- and PACAP-27-induced TSH
      release was suppressed by a simultaneous application of PACAP6-38. Application of
      high concentrations of PACAP6-38 alone caused a slight but significant
      stimulatory effect on the release of TSH. Frog VIP also stimulated TSH release
      from pituitary cells concentration-dependently. Frog SS1 (homologous to mammalian
      somatostatin-14) and SS2 (homologous to mammalian cortistatin) did not affect the
      basal release of TSH but caused a concentration-dependent suppression of the
      PACAP-38-induced release of TSH. These results suggest the involvement of
      multiple neuropeptides in the regulation of the release of TSH from the amphibian
      pituitary.

PMID- 16888214
TI  - A splice variant to PACAP receptor that is involved in spermatogenesis is
      expressed in astrocytes.
AB  - The pituitary adenylate cyclase-activating polypeptide (PACAP) receptor, PAC1,
      recognizes PACAP with a higher affinity than it recognizes vasoactive intestinal
      peptide (VIP) and belongs to the subfamily G protein-coupled receptors. So far,
      more than 10 different splice variants of PAC1 have been cloned from rat tissue.
      Interestingly, the various PAC1 splice variants exhibit different signaling
      pathways. These splice variants are suggested to play a functional role mostly in
      the brain as well as in the testes. The present article introduces PAC1(3a) that
      was originally discovered in testes as another potential regulator in rat
      astrocytes.

PMID- 16888215
TI  - Glucose activation of the glucagon receptor gene: functional dissimilarity with
      several other glucose response elements.
AB  - The glucagon receptor (GLR) expression is positively regulated by glucose. This
      regulation is allowed by the presence, in the promotor of the rat GLR gene, of a
      sequence feature similar to the two E-boxes motifs constituting the carbohydrate
      response elements (ChoRE) described for several glycolytic and lipogenic enzyme
      genes. Using reporter gene assays, we demonstrated here that, despite structural
      homologies with these ChoREs, the GLR gene glucose response element presents
      various functional dissimilarities. Testing glucose analogs, we demonstrated
      that, as for other genes, the glucose must be first phosphorylated. However, at
      variance with others homologue genes, our data showed the implication of the
      nonoxidative branch of the pentose phosphate pathway in the transmission of the
      glucose signal and lack of inhibition by adenosine monophosphate (AMP)-kinase.
      Furthermore, the activity of our reporter gene was strongly stimulated by
      butyrate, propionate, and acetate. This observation contrasts with fatty-acid
      induced inhibition of the glucose activation, observed for all other genes
      containing homolog ChoREs. We also showed that glucose and butyrate influence the
      reporter gene expression via different features.

PMID- 16888216
TI  - NAP, a peptide derived from the activity-dependent neuroprotective protein,
      modulates macrophage function.
AB  - NAP is an eight-amino acid neuroprotective peptide NAPVSIPQ; it is the smallest
      active element derived from the recently cloned activity-dependent
      neuroprotective protein (ADNP). NAP readily enters the brain from the blood. It
      will be important to learn whether NAP, in addition to its neuroprotective
      activity, also might influence immune-mediated inflammation. Here, we report
      that: (a) macrophages express ADNP; (b) expression of ADNP in macrophages
      responds to VIP; and (c) NAP downregulates the key inflammatory cytokines tumor
      necrosis factor (TNF-alpha), interleukin-16 (IL-16), and IL-12 in macrophages.
      These findings indicate that ADNP/NAP can play an important role in immune
      regulation as well as in neuroprotection, which may be mutually related
      processes.

PMID- 16888217
TI  - Mechanisms of VIP-induced neuroprotection against neonatal excitotoxicity.
AB  - Two VIP receptors, shared with a similar affinity by pituitary adenylate cyclase
      activating polypeptide (PACAP), have been cloned: VPAC1 and VPAC2. PHI binds to
      these receptors with a lower affinity. We previously showed that VIP protects
      against excitotoxic white matter damage in newborn mice. This article aimed to
      determine the receptor involved in VIP-induced neuroprotection. VIP effects were
      mimicked with a similar potency by VPAC2 agonists and PHI but not by VPAC1
      agonists, PACAP 27 or PACAP 38. VIP neuroprotective effects were lost in mice
      lacking VPAC2 receptor. In situ hybridization confirmed the presence of VPAC2
      mRNA. These data suggest that, in this model, VIP-induced neuroprotection is
      mediated by VPAC2 receptors. The pharmacology of this VPAC2 receptor seems
      unconventional as PACAP does not mimic VIP effects and PHI acts with a comparable
      potency.

PMID- 16888218
TI  - Comparative study of the effects of PACAP in young, aging, and castrated males in
      a rat model of Parkinson's disease.
AB  - We have previously shown that PACAP ameliorates the neurological symptoms and
      reduces the dopaminergic cell loss in young male rats, in a 6-hydroxydopamine (6
      OHDA)-induced lesion of the substantia nigra, a model of Parkinson's disease. In
      the present study, we compared the effects of PACAP in young, aging, and
      castrated males. Our results show that PACAP significantly reduced the
      dopaminergic cell loss in young and aging males. In castrated males, 6-OHDA did
      not induce such a severe cell loss, and it was not altered by PACAP. However,
      PACAP effectively ameliorated behavioral symptoms in all groups, with a degree of
      recovery depending on age and endocrine status.

PMID- 16888219
TI  - VIP and tolerance induction in autoimmunity.
AB  - Vasoactive intestinal peptide (VIP) is a potent anti-inflammatory agent with
      immunoregulatory properties, skewing the immune response to a Th2 pattern of
      cytokine production. Here, we studied the effect of treatment with VIP in the
      development of diabetes in nonobese diabetic (NOD) mice, an animal model of type
      1 diabetes. Mice treated with VIP from 4 weeks of age did not develop diabetes
      and showed milder insulitis than nontreated mice. The protective mechanism of VIP
      was associated with a reduction in the circulating levels of Th1 cytokines. In
      the pancreas of VIP-treated animals, regulatory T cell markers predominate, as
      indicated by the upregulation of FoxP3 and transforming growth factor-beta (TGF
      beta), and the downregulation of the transcription factor, T-bet. These findings
      indicate that VIP restores tolerance to pancreatic islets by promoting the local
      differentiation and function of regulatory T cells.

PMID- 16888220
TI  - Neuroprotective effect of PACAP against kainic acid-induced neurotoxicity in rat
      retina.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) is well known to
      protect delayed neuronal cell death in the brain of rodents. In order to
      investigate the neuroprotective action of PACAP in the retina, we examined the
      effects of PACAP on kainic acid (KA)-induced neurotoxicity in the rat retina.
      Many ganglion cells in the retina died after KA injection in the control group
      and PACAP treatment significantly promoted cell survival. These findings strongly
      suggest that PACAP plays very important roles in preventing cell death in the
      retina.

PMID- 16888221
TI  - PACAP stimulates the release of interleukin-6 in cultured rat Muller cells.
AB  - We have investigated the in vivo effect of PACAP on rat Muller cells that are the
      predominant glial element in the retina. Muller cells were treated with PACAP38,
      either alone or in the presence of the PACAP-selective antagonist, PACAP6-38.
      Cellular proliferation was determined by measuring the incorporation of
      bromodeoxyuridine, while interleukin-6 (IL-6) levels in the culture medium were
      examined using a B9 cell bioassay. In cultured rat Muller cells, the expression
      of PACAP receptor (PAC1-R) was assessed with immunohistochemistry using a PAC1-R
      specific antiserum. PACAP stimulated IL-6 production in Muller cells at a
      concentration as low as 10(-12) M, which was not sufficient to induce cell
      proliferation. This elevation of IL-6 production was significantly inhibited by
      PACAP6-38. These data suggest that Muller cells are one of the target cells for
      PACAP, stimulating the release of IL-6, and providing a mechanism whereby PACAP
      exerts a significant neuroprotective effect in the retina.

PMID- 16888222
TI  - VIP protects Th2 cells by downregulating granzyme B expression.
AB  - Selective differentiation of Th1/Th2 effectors contributes to cell- or antibody
      mediated immunity. Vasoactive intestinal peptide (VIP) induces Th2 responses by
      promoting Th2 differentiation and survival. Here we investigate the mechanisms of
      VIP-induced Th2 survival. Microarray and protein data indicate that VIP prevents
      the upregulation of granzyme B (GrB) in Th2, but not Th1 effectors. This is the
      first report of GrB expression and of its involvement in activation-induced
      apoptosis of T helper cells. The enhanced responsiveness of Th2 cells to VIP is
      probably due to the higher expression of VIP receptors and alternative signaling
      pathways. This study identifies GrB as a new significant player in Th1/Th2
      activation-induced cell death, and characterizes the mechanisms for the
      protective effect of VIP on Th2 survival.

PMID- 16888223
TI  - Serotonergic inhibition of intense jumping behavior in mice lacking PACAP
      (Adcyap1-/-).
AB  - Genetic manipulation of pituitary adenylate cyclase-activating polypeptide
      (PACAP) in mice has uncovered its involvement in psychomotor function. We
      previously observed that mice lacking the Adcyap1 gene encoding the neuropeptide
      PACAP (Adcyap1-/-) displayed intense jumping behavior when placed in a novel
      environment such as an open field. Here, we show that Adcyap1-/- mice manifest
      jumping behavior as early as at least 6 weeks of age when compared with wild-type
      mice and that the selective serotonin (5-HT) reuptake inhibitor, fluoxetine, as
      well as the serotonin precursor, 5-hydroxytryptophan, suppress jumping behavior.
      Our previous study showed a slight decrease in 5-HT metabolite, 5
      hydroxyindoleacetic acid (5-HIAA) in Adcyap1-/- mouse brain. Taken together,
      these results suggest that there is a developmental aspect to the jumping
      behavior seen in Adcyap1-/- mice, and that jumping behaviour may involve the
      serotonergic system.

PMID- 16888224
TI  - Pleiotropic functions of PACAP in the CNS: neuroprotection and neurodevelopment.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) is a pleiotropic
      neuropeptide that belongs to the secretin/glucagon/vasoactive intestinal peptide
      (VIP) family. PACAP prevents ischemic delayed neuronal cell death (apoptosis) in
      the hippocampus. PACAP inhibits the activity of the mitogen-activated protein
      kinase (MAPK) family, especially JNK/SAPK and p38, thereby protecting against
      apoptotic cell death. After the ischemia-reperfusion, both pyramidal cells and
      astrocytes increased their expression of the PACAP receptor (PAC1-R). Reactive
      astrocytes increased their expression of PAC1-R, released interleukin-6 (IL-6)
      that is a proinflammatory cytokine with both differentiation and growth-promoting
      effects for a variety of target cell types, and thereby protected neurons from
      apoptosis. These results suggest that PACAP itself and PACAP-stimulated secretion
      of IL-6 synergistically inhibit apoptotic cell death in the hippocampus. The PAC1
      R is expressed in the neuroepithelial cells from early developmental stages and
      in various brain regions during development. We have recently found that PACAP,
      at physiological concentrations, induces differentiation of mouse neural stem
      cells into astrocytes. Neural stem cells were prepared from the telencephalon of
      mouse embryos and cultured with basic fibroblast growth factor. The PAC1-R
      immunoreactivity was demonstrated in the neural stem cells. When neural stem
      cells were exposed to PACAP, about half of these cells showed glial fibrillary
      acidic protein (GFAP) immunoreactivity. This phenomenon was significantly
      antagonized by a PAC1-R antagonist (PACAP6-38), indicating that PACAP induces
      differentiation of neural stem cell into astrocytes. Other our physiological
      studies have demonstrated that PACAP acts on PAC1-R in mouse neural stem cells
      and its signal is transmitted to the PAC1-R-coupled G protein Gq but not to Gs.
      These findings strongly suggest that PACAP plays very important roles in
      neuroprotection in adult brain as well as astrocyte differentiation during
      development.

PMID- 16888225
TI  - The prenatal expression of secretin receptor.
AB  - Secretin is a classical gastrointestinal peptide while its neuroactive functions
      in the central nervous system have recently been consolidated. In the past, there
      was little information regarding the expression of secretin receptor in prenatal
      development. In this article, using mouse embryos and by in situ hybridization,
      secretin receptor transcripts were detected in several developing brain regions
      including the cerebellar primordium and choroid plexus. In the developing
      intestine, secretin receptor is present in the epithelial lining of the villi and
      the inner circular muscle. Interestingly, the transcripts for secretin receptor
      were also detected in the epicardium and myocardium of the developing heart as
      well as the glomerulus and collecting duct in the developing kidney. Taken
      together, our data suggest a potential pleiotrophic role of secretin during
      embryonic development.

PMID- 16888226
TI  - Cyclic AMP formation in C6 glioma cells: effect of PACAP and VIP in early and
      late passages.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive
      intestinal peptide (VIP) exert their actions via common receptors, VPAC1 and
      VPAC2, which are equally sensitive to both peptides, while PACAP stimulates its
      specific PAC1-type receptors. Both peptides potently stimulate cAMP production in
      different biological systems. In the present article, we examined the effects of
      PACAP and VIP on cAMP formation in C6 rat glioma cells used between passages 12
      28 (early) and 120-136 (late). In the presence of the PDE inhibitor IBMX (0.1
      mM), PACAP (0.1 microM) and VIP (1 microM) strongly stimulated cAMP synthesis in
      C6 cells in early passages, but not in C6 cells in late passages. In contrast,
      forskolin (10 microM), a direct activator of adenylyl cyclase, and isoprenaline
      (10 microM), a beta-adrenergic receptor agonist, strongly stimulated cAMP
      production in both early and late C6 cell passages. Concentration-dependent
      studies carried out in early passages with PACAP-38, PACAP-27, mammalian and
      chicken VIPs, and PHI/PHM peptides (1-5 microM) revealed that both forms of PACAP
      produced strong cAMP accumulation, VIP peptides were less effective than PACAP,
      while the cAMP effects of PHI/PHM peptides were noticeable only at the highest
      doses tested. These results suggest that C6 glioma cells in early passages
      possess functional PAC1 and possibly VPAC-type receptors, but either the density
      of PACAP/VIP receptors progressively declines or the PACAP/VIP receptor-Gs
      protein coupling becomes less effective through culture passages.

PMID- 16888227
TI  - Protective effects of PACAP in excitotoxic striatal lesion.
AB  - The present article investigated the effects of pituitary adenylate cyclase
      activating polypeptide (PACAP) treatment in a quinolinic acid (QA)-induced
      unilateral lesion of the striatum, a model of Huntington;s disease (HD). PACAP
      was given locally, preceding the lesion. Behavioral analysis was performed after
      1, 10, and 30 days, when motor activity and asymmetrical signs were evaluated.
      Three weeks after the treatment, a catalepsy test was performed by haloperidol
      administration, and finally histological assessment of the striatum was done. Our
      results show that PACAP treatment attenuated the behavioral deficits and reduced
      the number of lesioned neurons in the striatum.

PMID- 16888228
TI  - Characterization of the new photoaffinity probe (Bz2-K24)-VIP.
AB  - Site-directed mutagenesis and molecular modeling demonstrated that the N-terminal
      ectodomain of the VPAC1 receptor is a major site of vasoactive intestinal peptide
      (VIP) binding. Previous studies with the [Bpa6]-VIP and [Bpa22]-VIP probes
      (substitution with the photoactivable Bpa for the residues 6 and 22 in VIP)
      showed spatial approximation between the amino acids 6 and 22 of VIP and the 104
      108 and 109-119 sequences within the N-terminal ectodomain of the receptor,
      respectively. Here, we characterize the new probe (Bz2-K24)-VIP (substitution
      with the photoreactive Bz2-K for the residue 24 in VIP). After photolabeling and
      sequential digestions of the receptor, the 121-133 sequence of the N-terminal
      ectodomain was identified as the site of interaction. The N-terminal ectodomain
      of the VPAC1 receptor is therefore an affinity trap for the central part of VIP,
      at least between residues 6 and 24.

PMID- 16888229
TI  - PACAP receptor (PAC1-R) expression in rat and rhesus monkey thymus.
AB  - The expression of PACAP receptor (PAC1-R) was investigated in the thymus of rats
      and rhesus monkeys. In the rat thymus, PAC1-R positive cells were found in the
      intermediate type of thymic epithelial cells of the medulla. PAC1-R-positive
      cells were also seen in the thymic medulla of the rhesus monkey. The thymus
      showed unusual structures in some rhesus monkey dams (F0) and offspring (F1)
      exposed to 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD). Additionally, in these
      rhesus monkeys, PAC1-R expression was different from that in the control thymus.

PMID- 16888230
TI  - Characterization of the PAC1 variants expressed in the mouse heart.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP), a pleiotropic
      neuropeptide, exerts a variety of physiological functions through three types of
      G protein-coupled receptors, PAC1, VPAC1, and VAPC2. Characterization of the
      molecular forms of PAC1 in mouse heart revealed the presence of four types of
      variant receptors harboring the N or S variant in the first extracellular domain
      (EC1 domain) with or without the HOP1 insert in the third intracellular
      cytoplasmic loop (IC3 loop). Then, we assessed the binding affinity and ability
      to stimulate adenylyl cyclase of the PCA1 variant-expressing cells for PACAP.
      Adenylyl cyclase activation by PACAP was markedly influenced with the variant in
      the EC1 domain as well as that in the IC3 loop, in spite of a little difference
      in their binding properties. These data suggest that the combination of EC1
      domain variants and IC3 loop variants might account for the diversity of
      intracellular signaling, which might contribute to multiple functions of PACAP
      including a role in the cardiovascular system.

PMID- 16888231
TI  - Distribution of PACAP in the brain of the cartilaginous fish torpedo marmorata.
AB  - In this article, we investigated the distribution of pituitary adenylate cyclase
      activating polypeptide (PACAP) and its mRNA by immunohistochemistry, in situ
      hybridization, and RT-PCR techniques, in the central nervous system of the
      elasmobranch Torpedo marmorata. RT-PCR analysis showed that the CNS of T.
      marmorata expresses a messenger encoding PACAP. The immunohistochemistry and in
      situ hybridization patterns were partly overlapping, with a major expression in
      the hypothalamo-pituitary region and, surprisingly, in the saccus vasculosus. Our
      results show that, in T. marmorata, PACAP is synthesized and widely distributed
      in the CNS, suggesting an as yet unidentified role for this peptide in
      elasmobranch brain physiology.

PMID- 16888232
TI  - Involvement of protein kinase C in the PACAP-induced differentiation of neural
      stem cells into astrocytes.
AB  - Expression of members of the conventional protein kinase C (cPKC) family in the
      differentiation of mouse neural stem cells (NSCs) induced by pituitary adenylate
      cyclase-activating polypeptide (PACAP) was investigated. In particular,
      expression of the alpha and beta subtypes of cPKC in NSCs was observed. In
      response to activation by PACAP, cPKCbeta transiently increased twofold by day 2
      and returned to basal levels by day 4, suggesting that cPKCbeta might be
      responsible for the differentiation process.

PMID- 16888233
TI  - Role of two genes encoding PACAP in early brain development in zebrafish.
AB  - To study the role of pituitary adenylate cyclase-activating polypeptide (PACAP)
      in early brain development, we examined PACAP and its receptors for first
      expression and then separately knocked down the two forms of PACAP in zebrafish
      where development is rapid and observable. We injected morpholinos (antisense
      oligonucleotides) into fertilized eggs to block PACAP. Morphological changes in
      the brain were observed in embryos at 27 h post fertilization (hpf). Using in
      situ hybridization of early brain marker genes, we found that the most striking
      effects were an increase in pax2.1 expression in eye stalks associated with
      absence of either form of PACAP or an increase in eng2 and fgf8 in the midbrain
      hindbrain boundary after loss of PACAP2. These marker genes are among the
      earliest factors in the formation of the midbrain-hindbrain boundary, an early
      organizing center. We suggest that PACAP is a target gene with feedback
      inhibition on pax2.1, eng2, or fgf8 in specific brain areas. In the hindbrain,
      the absence of either form of PACAP had little effect, as shown by expression of
      ephA4 and meis1.1. During midbrain development, our evidence suggests that PACAP1
      can activate mbx. In both the diencephalon and/or forebrain, lack of PACAP1 or
      PACAP2 led to an increase in fgf8, again suggesting a suppressive effect of PACAP
      during development on these important genes that help to define cells in the
      forebrain. The early expression of transcripts for PACAP and its receptors by 0.5
      6 hpf make both PACAP1 and PACAP2 candidates for factors that influence brain
      development.

PMID- 16888234
TI  - A role for pituitary adenylate cyclase activating polypeptide (PACAP) in detrusor
      hyperreflexia after spinal cord injury (SCI).
AB  - Intrathecal administration of the PAC1 receptor antagonist, PACAP6-38 (10 nM),
      significantly (P < or = 0.05) reduced intermicturition, threshold and micturition
      pressures in chronic (3-6 weeks) spinal cord injured rats but intravesical
      administration (100-300 nM) was without effect. Intrathecal PACAP6-38 reduced the
      number and amplitude of nonvoiding bladder contractions observed after spinal
      cord injury (SCI). PACAP may contribute to detrusor hyperreflexia induced by SCI
      and PACAP antagonists may be a novel approach to reduce detrusor hyperreflexia
      after SCI.

PMID- 16888235
TI  - Impaired development of atherosclerosis in hyperlipidemic Ldlr-/- and ApoE-/-
      mice transplanted with Abcg1-/- bone marrow.
AB  - OBJECTIVE: The lungs of Abcg1-/- mice accumulate macrophage foam cells that
      contain high levels of unesterified and esterified cholesterol, consistent with a
      role for ABCG1 in facilitating the efflux of cholesterol from macrophages to high
      density lipoprotein (HDL) and other exogenous sterol acceptors. Based on these
      observations, we investigated whether loss of ABCG1 affects foam cell deposition
      in the artery wall and the development of atherosclerosis. METHODS AND RESULTS:
      Bone marrow from wild-type or Abcg1-/- mice was transplanted into Ldlr-/- or ApoE
      /- mice. After administration of a high-fat/high-cholesterol diet, plasma and
      tissue lipid levels and atherosclerotic lesion size were quantified and compared.
      Surprisingly, transplantation of Abcg1-/- bone marrow cells resulted in a
      significant reduction in lesion size in both mouse models, despite the fact that
      lipid levels increased in the lung, spleen, and kidney. Lesions of Ldlr-/- mice
      transplanted with Abcg1-/- cells contained increased numbers of apoptotic cells.
      Consistent with this observation, in vitro studies demonstrated that Abcg1-/-
      macrophages were more susceptible to oxidized low-density lipoprotein (ox-LDL)
      dependent apoptosis than Abcg1+/+ cells. CONCLUSIONS: Diet-induced
      atherosclerosis is impaired when atherosclerotic-susceptible mice are
      transplanted with Abcg1-/- bone marrow. The demonstration that Abcg1-/-
      macrophages undergo accelerated apoptosis provides a mechanism to explain the
      decrease in the atherosclerotic lesions.

PMID- 16888236
TI  - Angiotensin II type 1 receptor-mediated inflammation is required for choroidal
      neovascularization.
AB  - BACKGROUND: Choroidal neovascularization (CNV) is a critical pathogenesis in age
      related macular degeneration, the most common cause of blindness in the developed
      countries. The aim of the current study was to determine the involvement of the
      renin-angiotensin system (RAS) with the development of CNV, using human surgical
      samples and the murine model of laser-induced CNV. METHODS AND RESULTS: In the
      human and murine CNV tissues, the vascular endothelium expressed angiotensin II
      type 1 receptor (AT1-R), AT2-R, and angiotensin II. The CNV volume was
      significantly suppressed by treatment with an AT1-R blocker telmisartan, but not
      with an AT2-R blocker. AT1-R signaling blockade with telmisartan inhibited
      various inflammatory mechanisms including macrophage infiltration and
      upregulation of VEGF, intercellular adhesion molecule-1 (ICAM-1), MCP-1, and IL-6
      in the retinal pigment epithelium-choroid complex. A PPAR-gamma antagonist
      partially but significantly reversed the suppressive effect of telmisartan on in
      vivo induction of CNV and in vitro upregulation of ICAM-1 and MCP-1 in
      endothelial cells and IL-6 in macrophages, showing the dual contribution of PPAR
      gamma-agonistic and AT1-R-antagonistic actions in the telmisartan treatment.
      CONCLUSIONS: AT1-R-mediated inflammation plays a pivotal role in the development
      of CNV, indicating the possibility of AT1-R blockade as a novel therapeutic
      strategy to inhibit CNV.

PMID- 16888237
TI  - Blockade of angiotensin II receptors reduces the expression of receptors for
      advanced glycation end products in human endothelial cells.
AB  - OBJECTIVE: Receptors for advanced glycation end products (RAGEs) play crucial
      roles in atherogenesis. Because tumor necrosis factor alpha (TNFalpha) is
      expressed and upregulates RAGE expression in atherosclerotic lesions, the
      TNFalpha-RAGE interaction might be involved in the inflammatory process of
      atherogenesis. On the other hand, an angiotensin II type-1 receptor blocker
      (ARB), widely used as an antihypertensive drug, has been reported to have also
      antiatherosclerotic effects. Thus we investigated whether an ARB exerts
      antiatherosclerotic effects via inhibiting the TNFalpha-RAGE interaction. METHODS
      AND RESULTS: Stimulation of human endothelial cells with candesartan as well as
      olmesartan decreased TNFalpha-induced RAGE expression in both mRNA and protein
      levels along with the decrease in the activity of nuclear factor kappaB and the
      expression of inflammatory mediators such as vascular cell adhesion molecule
      (VCAM)-1. Both candesartan and olmesartan inhibited the binding of nuclear factor
      kappaB to the RAGE gene promoter. Furthermore, gene silencing of RAGE by RNA
      interference decreased the expression of TNFalpha-induced VCAM-1 in both mRNA and
      protein levels. CONCLUSIONS: RAGE contributes at least partially to the TNFalpha
      induced VCAM-1 expression in both mRNA and protein levels. Blockade of
      angiotensin II receptors might exert antiatherosclerotic effects via reducing
      TNFalpha-RAGE interaction.

PMID- 16888238
TI  - Repetitive fluctuations in blood glucose enhance monocyte adhesion to the
      endothelium of rat thoracic aorta.
AB  - BACKGROUND: The aim of this study was to elucidate the effect of repetitive
      fluctuations in blood glucose concentrations on monocyte adhesion to the aortic
      endothelium. METHODS AND RESULTS: Nonobese type 2 diabetes, Goto-Kakizaki (GK)
      rats were fed twice daily to induce repetitive postprandial glucose spikes. Then,
      we compared the number of monocytes adherent to the endothelium of thoracic aorta
      in these rats with that in rats fed ad libitum. To suppress the glucose spikes,
      rats were injected with an inhibitor of sodium-glucose transporter, phloridzin,
      just before each meal for 12 weeks. GK rats fed twice daily showed significantly
      lower HbA1c than GK rats fed ad libitum. However, the former group showed
      markedly higher number of monocytes adherent to the endothelium than the latter,
      together with increased arterial intimal thickening. Phloridzin significantly
      reduced the number of adherent monocytes in GK rats fed twice daily. CONCLUSIONS:
      Our data demonstrated that repetitive postprandial fluctuation in glucose
      concentration evokes monocyte adhesion to endothelial cells that was worse than
      that induced by stable hyperglycemia in vivo. Suppression of such fluctuations
      efficiently suppressed monocyte adhesion to the aortic endothelium.

PMID- 16888239
TI  - Quantitation and localization of matrix metalloproteinases and their inhibitors
      in human carotid endarterectomy tissues.
AB  - BACKGROUND: Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) play a
      central role in arterial wall remodeling, affecting stability of fibrous caps
      covering atherosclerotic plaques. The objective of this study was to determine
      the spatial distribution of TIMP mass and MMP mass and activity of carotid
      endarterectomy (CEA) tissues and relate it to the distribution of atherosclerotic
      lesions. METHODS AND RESULTS: Fresh CEA tissues were imaged by multicontrast MRI
      to generate 3D reconstructions. Tissue segments were cut transversely from the
      common, bifurcation, internal, and external regions. Segments were subjected to
      total protein extractions and analyzed by ELISA for MMP-2 and -9 and TIMP-1 and 
      2 mass and by zymography for gelatinase activity. Segments at or near the
      bifurcation with highly calcified lesions contained higher MMP levels and
      activity than segments distant from the bifurcation; highly fibrotic or necrotic
      plaque contained lower MMP levels and activity and higher TIMP levels. Fatty
      streak, fibroatheroma with hemorrhage and calcification, and fully occluded
      lesions were enriched in MMP-2, MMP-9, and TIMP-1 and TIMP-2, respectively.
      CONCLUSIONS: The spatial distribution of MMPs and TIMPs in carotid
      atherosclerotic lesions is highly heterogeneous, reflecting lesion location,
      size, and composition. This study provides the first semi-quantitative maps of
      differential distribution of MMPs and TIMPs over atherosclerotic plaques.

PMID- 16888240
TI  - Beta-adrenoceptor blockade markedly attenuates transgene expression from
      cytomegalovirus promoters within the cardiovascular system.
AB  - OBJECTIVE: The major immediate-early cytomegalovirus enhancer/promoter (MIECMV),
      widely used in cardiovascular gene therapy, contains several positively
      regulatory cAMP response elements (CRE). Catecholamine signaling via beta
      adrenoceptors might increase transgene expression from MIECMV, and if so, beta
      blockers may have a detrimental effect on the efficacy of clinical cardiovascular
      gene therapy strategies. METHODS AND RESULTS: Cultured smooth muscle cells were
      exposed to isoprenaline, atenolol, or propranolol, alone and in combination
      before infection with adenoviruses expressing beta-galactosidase. beta
      galactosidase expression was assayed 72 hours later. Isoprenaline increased
      transgene expression from MIECMV up to 8-fold (P<0.001), but had no effect on a
      promoter containing no CRE. The effect of isoprenaline was inhibited by beta
      blockade and by specific CRE-decoy oligonucleotides. Beta-blockers did not reduce
      transgene expression below basal levels. After adenovirus-mediated porcine
      intracoronary gene transfer, however, beta-blockade reduced beta-galactosidase
      expression by up to 250-fold compared with non-beta-blocked animals (P<0.01).
      CONCLUSIONS: Enhancement of promoter activity by endogenous catecholamines is
      essential for high-level transgene expression from MIECMV within the vasculature.
      Beta-blocker-mediated suppression of transgene expression from MIECMV in vascular
      tissues has a significant bearing on clinical studies of cardiovascular gene
      transfer. This is the first described interaction to our knowledge between widely
      prescribed pharmaceuticals and a commonly used promoter of clinical transgene
      expression.

PMID- 16888241
TI  - l-Caldesmon regulates proliferation and migration of vascular smooth muscle cells
      and inhibits neointimal formation after angioplasty.
AB  - OBJECTIVE: Light-type caldesmon (l-CaD) is a potent cytostatic and antiangiogenic
      protein that regulates cell growth and survival via modulation of the cell shape
      and cytoskeleton. The aim of this study is to explore the potential value of l
      CaD for use as a cytostatic agent to inhibit neointimal formation after
      angioplasty by suppressing vascular smooth muscle cell (VSMC) growth and
      migration. METHODS AND RESULTS: We tested the cytostatic function of l-CaD in
      cultured VSMCs using assays for apoptosis, cell proliferation, and migration, and
      evaluated the expression pattern of relevant signaling proteins (focal adhesion
      kinase [FAK] and mitogen-activated protein kinases) in VSMCs. Transfection of
      adenoviral vector encoding l-CaD (Ad-l-CaD) resulted in progressive loss of actin
      stress fibers and cell retraction. Enzyme-linked immunosorbent assay demonstrated
      that Ad-l-CaD transfection increased the apoptosis rate by 75% and reduced BrdU
      uptake by 49%. Furthermore, transfection of Ad-l-CaD inhibited migration of VSMCs
      induced by platelet-derived growth factor-BB (PDGF) by 36% (P<0.05).
      Immunoblotting analysis revealed that l-CaD overexpression reduced PDGF-induced
      phosphorylation of both FAK and extracellular signal regulated-kinase (ERK). In
      balloon-injured rat carotid arteries, Ad-l-CaD transfection inhibited neointimal
      formation by 37% (P<0.05) without delaying re-endothelialization at 14 days.
      CONCLUSIONS: Overexpression of l-CaD suppressed cell growth and survival in VSMCs
      and inhibited neointimal formation after experimental angioplasty, partly by
      regulating the cytoskeletal tension-FAK-ERK axis.

PMID- 16888242
TI  - FHL2/SLIM3 decreases cardiomyocyte survival by inhibitory interaction with
      sphingosine kinase-1.
AB  - Sphingosine kinase-1 (SK1) is a key enzyme catalyzing the phosphorylation of
      sphingosine to sphingosine-1-phosphate (S1P). Recent studies suggest that SK1,
      and its product S1P, regulate diverse biological functions, including cell
      growth, differentiation, proliferation, and apoptosis. S1P may also play an
      important role in cardiac development and ischemic preconditioning, but the
      mechanism underlying these effects is not known. Using a yeast 2-hybrid screen
      with SK1 as bait and a cardiac cDNA library to identify novel proteins involved
      in regulating SK1 activity in cardiomyocytes, we identified the LIM-only factor
      FHL2 (SLIM3) as a SK1-interacting protein in both yeast and mammalian cells.
      FHL2, but not FHL1 or FHL3, interacted with SK1, and FHL2 colocalized with SK1 in
      the cytoplasm. The interaction sites with SK1 consisted of at least 4 LIM domains
      in FHL2, whereas the C-terminal portion of SK1 mediates the binding of FHL2 in
      SK1. Overexpression of FHL2 attenuated the activity and antiapoptotic effects of
      SK1. Indeed, endothelin-1, which is a potent survival factor in cardiomyocytes,
      inhibited FHL2-SK1 association and increased SK1 activity. These findings
      indicate that FHL2 is a novel inhibitor of SK1 activity in cardiomyocytes and
      suggest that targeting FHL2 for inhibition may prevent myocardial apoptosis
      through activation of SK1.

PMID- 16888243
TI  - Regionalized sequence of myocardial cell growth and proliferation characterizes
      early chamber formation.
AB  - Increase in cell size and proliferation of myocytes are key processes in cardiac
      morphogenesis, yet their regionalization during development of the heart has been
      described only anecdotally. We have made quantitative reconstructions of
      embryonic chicken hearts ranging in stage from the fusion of the heart-forming
      fields to early formation of the chambers. These reconstructions reveal that the
      early heart tube is recruited from a pool of rapidly proliferating cardiac
      precursor cells. The proliferation of these small precursor cells ceases as they
      differentiate into overt cardiomyocytes, producing a slowly proliferating
      straight heart tube composed of cells increasing in size. The largest cells were
      found at the ventral side of the heart tube, which corresponds to the site of the
      forming ventricle, as well as the site where proliferation is reinitiated. The
      significance of these observations is 2-fold. First, they support a model of
      early cardiac morphogenesis in 2 stages. Second, they demonstrate that regional
      increase in size of myocytes contributes significantly to chamber formation.

PMID- 16888244
TI  - Life, sudden death, and intracellular calcium.

PMID- 16888245
TI  - Myosin light chain 2 into the mainstream of cardiac development and
      contractility.

PMID- 16888246
TI  - Containing hypertrophy with a PICOT fence.

PMID- 16888247
TI  - Small molecule approaches for promoting ischemic tissue vascularization.

PMID- 16888248
TI  - Does 2-methoxyestradiol represent the new and improved hormone replacement
      therapy for atherosclerosis?

PMID- 16888249
TI  - Rho-kinase: a potential link between hypercholesterolemia and abnormal vascular
      smooth muscle contraction.

PMID- 16888250
TI  - Recent advances of intervention to inhibit progression of carotid intima-media
      thickness in patients with type 2 diabetes mellitus.
AB  - BACKGROUND AND PURPOSE: Type 2 diabetes is associated with a high cardiovascular
      morbidity and mortality. Recent advances of intervention studies in type 2
      diabetes with use of carotid intima-media thickness (CIMT) measurement as a
      surrogate end point may allow for better understanding of the undetermined
      process of atherosclerosis, the effect of interventions, and the usefulness of
      CIMT to inhibit events of cardiovascular disease. SUMMARY OF REVIEW: Data were
      available from 11 studies (n=1578) in subjects with type 2 diabetes (including
      impaired glucose tolerance, n=132) that evaluated the effect of interventions on
      change in CIMT. The overall weighed rate of change in mean CIMT based on data
      among control groups (ie, type 2 diabetes without interventions) was 0.034 mm/y
      (95% CI, 0.029 to 0.039; median SD, 0.054), in which mean HbA(1c) was 7.86% (95%
      CI, 7.72 to 8.00; median SD, 1.5). A significant close correlation of HbA(1c)
      with rate of CIMT change was found (R(2)=0.35, P=0.01). Agents for lowering of
      blood glucose, platelet activation, or blood pressure significantly reduced the
      CIMT increase, independent of blood glucose control. This implies that other
      mechanisms of such agents to diminish CIMT increase should be explored.
      CONCLUSIONS: CIMT measurement may contribute to elucidating the short- and/or
      long-term effect of interventions on the rate of change in CIMT in relation to
      the levels of various risk factors. Although the method needs further
      standardization, pharmacological interventions are likely to inhibit progression
      of CIMT, leading to a reduction of cardiovascular events.

PMID- 16888251
TI  - Intra-arterial thrombolysis is the treatment of choice for basilar thrombosis:
      con.

PMID- 16888252
TI  - Intra-arterial thrombolysis is the treatment of choice for basilar thrombosis:
      pro.

PMID- 16888253
TI  - Hyperperfusion syndrome after intracranial angioplasty and stent placement.

PMID- 16888254
TI  - Cerebral blood flow thresholds in acute stroke triage.

PMID- 16888257
TI  - Eligibility for anticoagulation in elderly patients with atrial fibrillation.

PMID- 16888258
TI  - Role of hyperglycemia and glutamate receptors in ischemic injury in acute
      cerebral infarction.

PMID- 16888260
TI  - Measuring treatment effect in acute stroke trials.

PMID- 16888261
TI  - Controversial molecular classification of human cerebrovascular malformations.

PMID- 16888262
TI  - Long-term outcome after stroke: evaluating health-related quality of life using
      utility measurement.

PMID- 16888263
TI  - Cluster randomized pilot controlled trial of an occupational therapy intervention
      for residents with stroke in UK care homes.
AB  - BACKGROUND AND PURPOSE: A pilot evaluation of an occupational therapy
      intervention to improve self-care independence for residents with stroke-related
      disability living in care homes was the basis of this study. METHODS: A cluster
      randomized controlled trial with care home as the unit of randomization was
      undertaken in Oxfordshire, UK. Twelve homes (118 residents) were randomly
      allocated to either intervention (6 homes, 63 residents) or control (6 homes, 55
      residents). Occupational therapy was provided to individuals but included carer
      education. The control group received usual care. Assessments were made at
      baseline, postintervention (3 months) and at 6-months to estimate change using
      the Barthel Activity of Daily Living Index (BI) scores, "poor global outcome",
      (defined as deterioration in BI score, or death) and the Rivermead Mobility
      Index. RESULTS: At 3 months BI score in survivors had increased by 0.6 (SD 3.9)
      in the intervention group and decreased by 0.9 (2.2) in the control group; a
      difference of 1.5 (95% CI allowing for cluster design, -0.5 to 3.5). At 6 months
      the difference was 1.9 (-0.7 to 4.4). Global poor outcome was less common in the
      intervention group. At 3 months, 20/63 (32%) were worse/dead in the intervention
      group compared with 31/55 (56%) in the control group, difference -25% (-51% to
      1%). At 6 months the difference was similar, -26% (-48% to -3%). Between-group
      changes in Rivermead Mobility Index scores were not significantly different.
      CONCLUSIONS: Residents who received an occupational therapy intervention were
      less likely to deteriorate in their ability to perform activities of daily
      living.

PMID- 16888265
TI  - Sex-based differences in the effect of intra-arterial treatment of stroke: a plea
      to stop torturing the old data and do large trials!

PMID- 16888264
TI  - Plaque echolucency is not associated with the risk of stroke in carotid stenting.
AB  - BACKGROUND AND PURPOSE: Plaque characteristics are suggested to play a
      potentially important role as risk factors for poor outcome after carotid artery
      stenting (CAS). We therefore correlated objectively and subjectively determined
      carotid plaque morphology with neurological complications after CAS. METHODS: We
      enrolled 698 consecutive patients undergoing elective CAS from a prospective
      single-center registry database and classified the preinterventional plaque
      status according to gray-scale median levels and the standardized Beletsky and
      Gray-Weale plaque scores. Patients were followed for 30-day neurological
      complications. RESULTS: Neurological complications including transient ischemic
      attack, minor and major stroke occurred in 5.9% (41/698) of the patients. Median
      gray-scale median, Beletsky and Gray-Weale scores were 45 (interquartile range
      [IQR] 25 to 70), 3.0 (IQR 2.0 to 3.0) and 2.0 (IQR 2.0 to 3.0), respectively.
      None of the scores was significantly associated with adverse outcome adjusting
      for traditional risk factors, medication, preinterventional symptoms, degree of
      stenosis, contralateral occlusion and use of cerebral protection, neither with
      respect to all neurological complications nor with respect to stroke and death
      (all P>0.05). CONCLUSIONS: Plaque echolucency measured by objective and
      subjective grading did not identify patients with an increased risk of peri
      interventional neurological events. Evaluation of plaque echolucency therefore
      cannot be recommended for risk stratification in CAS patients.

PMID- 16888266
TI  - Tandem internal carotid artery/middle cerebral artery occlusion: an independent
      predictor of poor outcome after systemic thrombolysis.
AB  - BACKGROUND AND PURPOSE: Although tandem internal carotid artery/middle cerebral
      artery (MCA; TIM) occlusion has been associated with low recanalization rate
      after IV tissue plasminogen activator (tPA), its independent contribution on
      stroke outcome remains unknown. Moreover, whether the relative resistance to
      thrombolysis in tandem lesions varies depending on the location of MCA clot
      remains uncertain. METHODS: Two hundred and twenty-one consecutive stroke
      patients with an acute MCA occlusion treated with IV tPA were studied. Emergent
      carotid artery ultrasound and transcranial Doppler (TCD) examinations were
      performed in all patients before treatment. Recanalization was assessed on TCD at
      2 hours of tPA bolus. National Institutes of Health Stroke Scale (NIHSS) scores
      were obtained at baseline and after 24 hours. Modifed Rankin Scale score was used
      to assess outcome at 3 months. RESULTS: Median prebolus NIHSS score was 16
      points. On TCD, 156 (71.6%) patients had a proximal and 65 (29.4%) a distal MCA
      occlusion. TIM occlusion was identified in 44 (19.9%) patients. Eighteen (41.9%)
      patients with and 123 (69.5%) without TIM lesions achieved an MCA recanalization
      (P=0.01). In a logistic regression model, hyperglycemia >140 mg/dL (odds ratio
      [OR] 3.3, 95% CI, 1.6 to 6.8) and the presence of TIM occlusion (OR 2.8, 95% CI,
      1.1 to 6.9) emerged as independent predictors of absence of recanalization.
      However, the independent contribution of TIM lesions on poor response to
      thrombolysis varied depending on the location of MCA occlusion. TIM occlusion
      independently predicted resistance to thrombolysis in patients with proximal (OR
      4.63, 95% CI, 1.79 to 11.96), but not in those with distal MCA occlusion.
      Patients with TIM occlusion had worse short- (P<0.0001) and long-term (P<0.0001)
      clinical outcome. CONCLUSIONS: TIM occlusion independently predicts poor outcome
      after IV thrombolysis. However, its impact varies depending on the location of
      MCA clot. Therefore, emergent carotid ultrasound plus TCD examinations may
      improve the selection of patients for more aggressive reperfusion strategies.

PMID- 16888267
TI  - Basilar artery thrombosis: recanalization is the key.

PMID- 16888268
TI  - Cerebral blood flow threshold of ischemic penumbra and infarct core in acute
      ischemic stroke: a systematic review.

PMID- 16888269
TI  - Sex-based differences in the effect of intra-arterial treatment of stroke:
      analysis of the PROACT-2 study.
AB  - BACKGROUND AND PURPOSE: Sex influences outcome after intravenous thrombolysis. In
      a combined analysis of the tissue plasminogen activator clinical trials, a sex-by
      treatment interaction was observed. We sought to confirm that observation in an
      independent data set. METHODS: Data were from the Pro-Urokinase for Acute
      Cerebral Thromboembolism-2 (PROACT-2) trial. Baseline factors were compared by
      sex. The primary outcome was an assessment of a sex-by-treatment interaction term
      within a logistic regression model, using a modified Rankin Scale score <or=2 at
      90 days as the binary outcome. We also assessed whether there were differences in
      CT-scan appearance and recanalization at 2 hours post-treatment. RESULTS: In the
      PROACT-2 study of intra-arterial stroke thrombolysis, in both women and men,
      prourokinase resulted in better outcomes than control. A sex by prourokinase
      treatment interaction was observed, with women showing a larger treatment effect
      (20% absolute benefit) compared with men (10% absolute benefit). The reason for
      this interaction is that thrombolytic treatment nullifies the worse outcome for
      untreated women compared with men. The reasons for effect modification do not
      include improved recanalization at 2 hours among women. CONCLUSIONS: Women with
      middle cerebral artery ischemic stroke benefit more from intra-arterial therapy.
      Further study of how sex affects stroke outcome is needed.

PMID- 16888270
TI  - Randomized controlled trial of acetylsalicylic acid in aneurysmal subarachnoid
      hemorrhage: the MASH Study.
AB  - BACKGROUND AND PURPOSE: A previous systematic review of randomized trials
      suggested a positive effect of antiplatelet therapy in patients with aneurysmal
      subarachnoid hemorrhage (SAH). We performed a randomized controlled trial to
      assess whether acetylsalicylic acid (ASA) reduces the risk of delayed ischemic
      neurological deficit (DIND) in patients with SAH. METHODS: Criteria for inclusion
      were aneurysm treatment within 4 days after SAH. Trial medication (14 daily
      suppositories with 100 mg ASA or placebo) was started within 12 hours after
      aneurysm treatment. Analysis for the primary outcome event DIND was made
      according to the "on-treatment" principle and for the secondary outcome measures
      "poor outcome" and "nonexcellent outcome" according to the "intention-to-treat"
      principle. RESULTS: Inclusion was stopped after the second interim analysis, when
      161 of the planned 200 patients were included, because by then the chances of a
      positive effect were negligible. At the final analysis, ASA did not reduce the
      risk of DIND (hazard ratio, 1.83; 95% CI, 0.85 to 3.9). The relative risk
      reduction for poor outcome was 21% (relative risk, 0.79; 95% CI, 0.38 to 1.6).
      CONCLUSIONS: ASA given after aneurysm treatment does not appreciably reduce the
      occurrence of DIND.

PMID- 16888271
TI  - Additive role of plasma von Willebrand factor levels to clinical factors for risk
      stratification of patients with atrial fibrillation.
AB  - BACKGROUND AND PURPOSE: To aid decisions for thromboprophylaxis in atrial
      fibrillation (AF), several risk stratification schemes that predict stroke risk
      according to clinical and echocardiographic features have been published. von
      Willebrand factor (vWf) is a plasma markers of endothelial damage/dysfunction and
      is associated with the risk of stroke and vascular events in AF patients. This
      study determined the additive role of plasma vWf levels to clinical factors for
      risk stratification in patients with AF. METHODS: We classified 994 AF patients
      who were enrolled in the SPAF III trial as being at low, moderate, or high risk
      of stroke and thromboembolism according to the Birmingham and CHADS(2) risk
      stratification schemes. vWf levels were classified as elevated when >or=158 IU
      /dL. Rates of ischemic stroke and vascular events within each clinical risk
      stratum with and without plasma vWf levels were compared. RESULTS: The accuracy
      of both clinical risk stratification schemes was similar for predicting event
      rates (Birmingham: ischemic strokes, 0.642; vascular events, 0.670; CHADS(2):
      ischemic strokes, 0.672; vascular events, 0.672). Subsequent addition of
      categorized vWf levels to both clinical risk stratification schemes further
      refined risk stratification for stroke and vascular events. When added to the
      Birmingham and CHADS(2) clinical risk stratification, high vWf levels were
      independently associated with a risk of vascular events (hazard ratio, 2.05; 95%
      confidence interval, 1.30 to 3.22 and 2.01, 1.27 to 3.18 with Birmingham and
      CHADS(2), respectively) but not ischemic stroke. CONCLUSIONS: When added to
      clinical risk stratification schemes (Birmingham; CHADS(2)), plasma vWf levels
      refined clinical risk stratification for stroke and vascular events among AF
      patients. vWf levels may aid decisions about thromboprophylaxis, particularly
      among AF patients at moderate risk.

PMID- 16888272
TI  - Candesartan- and atenolol-based treatments induce different patterns of carotid
      artery and left ventricular remodeling in hypertension.
AB  - BACKGROUND AND PURPOSE: Angiotensin receptor blocker (ARB)-based treatment
      reduces cardiovascular events and stroke more than does beta-blocker-based
      treatment despite similar blood pressure (BP) reduction. We investigated whether
      these treatments have different effects on cardiac and large-artery remodelling
      and evaluated the relation of arterial remodelling to hemodynamic changes in
      subjects with hypertension. METHODS: We compared the treatment effects of an ARB
      (candesartan cilexetil)-based regimen and a beta-blocker (atenolol)-based regimen
      for 52 weeks on common carotid artery (CCA) and left ventricular structure in
      hypertensive patients in a randomized, double-blind study. Clinic brachial BP and
      24-hour ambulatory BP, carotid BP, left ventricular mass index, CCA intima-media
      thickness, lumen diameter, intima-media area, and carotid blood flow were
      measured. Distensibility, circumferential tensile stress, Young's elastic modulus
      (E(m)), and shear stress (tau) in the CCA were also calculated. RESULTS: Both
      candesartan and atenolol reduced intima-media thickness and intima-media area and
      increased distensibility to similar extents after 52 weeks of treatment. Despite
      similar reductions in BP, treatment with atenolol resulted in a lesser reduction
      in left ventricular mass index, a decrease in lumen diameter, and a reduction in
      carotid blood flow compared with candesartan. CONCLUSIONS: BP-independent effects
      of ARB on cardiac and arterial structure may contribute to the beneficial effects
      of these agents on cardiovascular disease.

PMID- 16888273
TI  - Course of platelet activation and platelet-leukocyte interaction in
      cerebrovascular ischemia.
AB  - BACKGROUND AND PURPOSE: Platelet activation plays a crucial role in the
      pathophysiology of cerebral ischemia. The aim of this study was to investigate
      the contribution of platelet activation and leukocyte-platelet interactions to
      the disease. METHODS: One hundred thirty-five patients with transient ischemic
      attack (TIA) or stroke were enrolled in this single-center study. They underwent
      cranial computer tomography within 24 hours of clinical onset and after 3 months,
      and systemic venous blood samples were drawn. Platelet activation (CD62P
      expression), leukocyte activation (L-selectin expression), and the appearance of
      platelet-specific antigens on leukocytes as an index of platelet-leukocyte
      aggregation were measured by flow cytometric techniques in the acute state and at
      3-month follow-up. RESULTS: Patients with a completed stroke or TIA had
      significantly increased circulating platelet-leukocyte aggregates, increased P
      selectin expression on platelets, and decreased L-selectin expression in the
      acute state compared with the control group (healthy volunteers). No differences
      in regard to the tested activation markers could be detected between patients
      with stroke or TIA in the acute phase of the disease. However, platelet and
      leukocyte activations were normalized after 3 months in patients with TIA,
      whereas leukocyte activation (reduced L-selectin expression) remained in stroke
      patients. CONCLUSIONS: In patients with TIA and completed stroke, platelet and
      leukocyte activation is substantially enhanced in the acute phase of the disease.
      The sustained leukocyte activation observed in stroke but not in TIA patients at
      3-month follow up might play a pathophysiological role in the course of the
      disease.

PMID- 16888274
TI  - Severe sleep apnea and risk of ischemic stroke in the elderly.
AB  - BACKGROUND AND PURPOSE: Convincing evidence of a causal relationship between
      sleep apnea and stroke has been shown recently in several prospective, well
      designed studies. However, these studies have focused on middle-aged people,
      excluding the elderly population from analysis. To investigate whether sleep
      apnea represents an independent risk factor in this population, we performed a
      prospective longitudinal study in a population-based cohort of subjects from 70
      to 100 years old. METHODS: Within the context of the Vitoria Sleep Project, a
      population-based study designed to investigate the prevalence of sleep apnea in
      the population of Vitoria, Spain, we performed a 6-year longitudinal study in a
      subsample cohort of 394 noninstitutionalized, initially event-free subjects (70
      to 100 years old, median 77.28 years, 57.1% males). Demographic and
      polysomnographic data and known confounding factors (age, sex, smoking and
      alcohol consumption status, body mass index, systolic and diastolic blood
      pressure, total serum cholesterol levels, and the presence or absence of diabetes
      mellitus, atrial fibrillation, and hypertension) were assessed at baseline.
      Hazard ratio for developing an ischemic stroke in relation to the apnea-hypopnea
      index at baseline was calculated. RESULTS: Over the 6-year follow-up period, 20
      ischemic strokes were registered. After adjustment for confounding factors,
      subjects with severe obstructive sleep apnea hypopnea (defined as apnea-hypopnea
      index >or=30) at baseline had an increased risk of developing a stroke (hazard
      ratio=2.52, 95% CI=1.04 to 6.01, P=0.04). CONCLUSIONS: This study shows that
      severe obstructive sleep apnea hypopnea (defined as apnea-hypopnea index >or=30)
      increases the risk of ischemic stroke in the elderly population, independent of
      known confounding factors.

PMID- 16888275
TI  - Thyroid autoimmunity and spontaneous cervical artery dissection.
AB  - BACKGROUND AND PURPOSE: The possibility that a disorder of immunity might have a
      role in the mechanism of local inflammatory alterations leading to spontaneous
      cervical artery dissection (sCAD) has been recently advocated. METHODS: We
      explored this hypothesis in a case-control study, including patients with sCAD
      (n=29) and patients with non-CAD ischemic stroke (non-CAD; n=29). Serum levels of
      antithyroperoxidase, antithyroglobulin, and antithyroid-stimulating hormone
      receptor antibodies, antinuclear antibodies, antineutrophil cytoplasmic
      antibodies, antidouble-stranded deoxyribonucleic acid antibodies, antiextractable
      nuclear antigen antibodies, rheumatoid factor, C3 and C4 complement fraction, and
      cryoglobulins were measured in all subjects. RESULTS: Antithyroid autoimmunity
      was found in 31.0% (9 of 29) of patients with sCAD and 6.9% (2 of 29) of patients
      with non-CAD ischemic stroke (P=0.041). CONCLUSIONS: Autoimmunity may be involved
      in the process of local inflammation related to sCAD occurrence. The hypothesis
      that the arterial disease might be one phenotypic expression of a generalized
      activation of immunity warrants further investigations.

PMID- 16888276
TI  - Dental and periodontal status and risk for progression of carotid
      atherosclerosis: the inflammation and carotid artery risk for atherosclerosis
      study dental substudy.
AB  - BACKGROUND AND PURPOSE: Dental and periodontal disease are potentially involved
      in the pathogenesis of atherosclerosis. We investigated whether dental and
      periodontal status is associated with the presence and future progression of
      carotid stenosis. METHODS: We randomly selected 411 of 1268 participants from the
      prospective Inflammation and Carotid Artery Risk for Atherosclerosis Study and
      evaluated dental and periodontal status and oral hygiene at baseline measuring
      three World Health Organization-validated indices: DMFT (decayed, missing, filled
      teeth), SLI (Silness-Loe Index), and CPITN (community periodontal index for
      treatment needs), respectively. The degree of carotid stenosis was measured by
      duplex ultrasound at baseline and after median 7.5 months (range=6 to 9 months)
      to identify patients with progressive carotid stenosis. RESULTS: DMFT (P<0.01),
      SLI (P=0.048), CPITN (P=0.007), and edentulousness (P=0.007) were associated with
      the baseline degree of carotid stenosis. Atherosclerosis progression was observed
      in 48 of 411 patients (11.7%). DMFT (adjusted odds ratio [OR]=1.11, 95% CI=1.01
      to 1.22, P=0.032) and SLI (adjusted OR=1.77, 95% CI=1.09 to 2.79, P=0.021), but
      not CPITN (adjusted OR=1.51, 95% CI=0.89 to 2.45, P=0.16) were significant
      predictors of disease progression, irrespective of traditional cardiovascular
      risk factors and the baseline degree of stenosis. Edentulous patients had a
      significantly increased risk for disease progression as compared with patients
      with teeth (adjusted OR=2.10, 95% CI=1.06 to 4.16, P=0.33). CONCLUSIONS: Dental
      status, oral hygiene, and particularly tooth loss are associated with the degree
      of carotid stenosis and predict future progression of the disease.

PMID- 16888277
TI  - Incidence of new brain lesions after carotid stenting with and without cerebral
      protection.
AB  - BACKGROUND AND PURPOSE: Diffusion-weighted imaging (DWI) may be a useful tool to
      evaluate the efficacy of cerebral protection devices in preventing thromboembolic
      complications during carotid angioplasty and stenting (CAS). The goals of this
      study were (1) to compare the frequency, number, and size of new DWI lesions
      after unprotected and protected CAS; and (2) to determine the clinical
      significance of these lesions. METHODS: DWI was performed immediately before and
      within 48 hours after unprotected or protected CAS. Clinical outcome measures
      were stroke and death within 30 days. RESULTS: The proportion of patients with
      any new ipsilateral DWI lesion (49% versus 67%; P<0.05) as well as the number of
      new ipsilateral DWI lesions (median=0; interquartile range [IQR]=0 to 3 versus
      median=1; IQR=0 to 4; P<0.05) were significantly lower after protected (n=139)
      than unprotected (n=67) CAS. The great majority of these lesions were
      asymptomatic and less than 10 mm in diameter. Although there were no significant
      differences in clinical outcome between patients treated and not treated with
      protection devices (7.5% versus 4.3%, not significant), the number of new DWI
      lesions was significantly higher in patients who developed a stroke (median=7.5;
      IQR=1.5 to 17) than in patients who did not (median=0; IQR=1 to 3.25; P<0.01).
      CONCLUSIONS: The use of cerebral protection devices significantly reduces the
      incidence of new DWI lesions after CAS of which the majority are asymptomatic and
      less than 10 mm in diameter. The frequent occurrence of these lesions and their
      close correlation with the clinical outcome indicates that DWI could become a
      sensitive surrogate end point in future randomized trials of unprotected versus
      protected CAS.

PMID- 16888278
TI  - Basilar artery diameter and 5-year mortality in patients with stroke.
AB  - BACKGROUND AND PURPOSE: Few and conflicting data exist on the case fatality rate
      in stroke patients with basilar artery dolichoectasia. We analyzed basilar artery
      characteristics (diameter, height of bifurcation, transverse position) and 5-year
      mortality (all-cause, nonstroke vascular, and stroke) in patients with brain
      infarction. METHODS: The basilar artery diameter was measured with a 16-diopter
      lens in 466 consecutively recruited patients with brain infarction confirmed by
      magnetic resonance imaging. The height of the bifurcation and the transverse
      position of the basilar artery were assessed on semiquantitative scales. Patients
      were followed up for a median of 5.3 years (range, 1.5 to 6.6) and were
      classified as having had stroke, nonstroke vascular, and nonvascular death
      according to the French national registry of death certificates. RESULTS: Of the
      157 deaths, 88 were vascular (including 54 stroke deaths). Basilar artery
      diameter was associated with an increased 5-year stroke mortality rate but not
      with all-cause or nonstroke vascular mortality. The adjusted hazard ratio (HR) of
      stroke mortality per 1-mm increase in basilar artery diameter was 1.23 (95%
      confidence interval [CI], 1.07 to 1.41). A higher risk of stroke death was
      associated with basilar artery diameter at the 95th percentile (diameter >4.3 mm;
      adjusted HR 3.69; 95% CI, 1.63 to 8.38) and the height of bifurcation (adjusted
      HR for score >1, 2.08; 95% CI, 0.93 to 4.68) but not with transverse position.
      CONCLUSIONS: Basilar artery diameter was independently associated with
      cerebrovascular mortality. A diameter >4.3 mm may be a marker for a high risk of
      fatal stroke.

PMID- 16888279
TI  - The minimal instrumentation requirements for Hoechst side population analysis:
      stem cell analysis on low-cost flow cytometry platforms.
AB  - The Hoechst side population (SP) technique is a critical method of identifying
      stem cells and early progenitors in rodent, nonhuman primate, and human
      hematopoietic and nonhematopoietic tissues. In this technique, the cell-permeable
      DNA-binding dye Hoechst 33342 is loaded into the cell population of interest;
      stem cells and early progenitors subsequently pump this dye out via an ATP
      binding cassette membrane pump-dependent mechanism, resulting in a low
      fluorescence "tail" (the SP) when the cells are analyzed by flow cytometry. This
      population contains stem cells and early progenitors. One significant drawback of
      this method is the requirement of an UV laser to excite the Hoechst 33342.
      Unfortunately, flow cytometers equipped with UV sources are expensive to own and
      operate and are not readily available to many laboratories or institutions. In
      the interests of designing a less expensive flow cytometric system for stem cell
      analysis, we determined the minimum UV excitation and instrumentation
      requirements for measuring Hoechst SP. Less than 3 mW of UV laser output was
      required for adequate resolution of Hoechst SP on two cuvette-based flow
      cytometers, one of which was a simple, inexpensive benchtop analyzer (the Quanta
      Analyzer; NPE Systems). Furthermore, Hoechst SP could also be adequately resolved
      on this epifluorescence-based cytometer platform using two nonlaser UV sources, a
      mercury arc lamp with a UV bandpass filter and a UV-emitting light-emitting
      diode. These results suggest that an economical flow cytometric system can be
      designed that is capable of resolving Hoechst SP, with a cost far lower than most
      UV laser-equipped commercial systems. An inexpensive system of this type would
      make Hoechst SP analysis available to a much broader group of stem cell
      investigators.

PMID- 16888280
TI  - Sequential analysis of alpha- and beta-globin gene expression during
      erythropoietic differentiation from primate embryonic stem cells.
AB  - The temporal pattern of embryonic, fetal, and adult globin expression in the
      alpha (zeta --> alpha) and beta (epsilon --> gamma and gamma --> beta) clusters
      were quantitatively analyzed at the transcriptional and translational levels in
      erythrocytes induced from primate embryonic stem cells in vitro. When vascular
      endothelial growth factor receptor-2(high) CD34(+) cells were harvested and
      reseeded onto OP9 stromal cells, two-wave erythropoiesis occurred sequentially.
      Immunostaining and real-time reverse transcription-polymerase chain reaction
      analyses of floating mature erythrocytes revealed that globin switches occurred
      in parallel with the erythropoietic transition. Colony-forming assays showed
      replacement of primitive clonogenic progenitor cells with definitive cells during
      culturing. A decline in embryonic zeta- and epsilon-globin expression at the
      translational level occurred in individual definitive erythroid progenitors.
      Expression of beta-globin in individual definitive erythroid progenitors was
      upregulated in the presence of OP9 stromal cells. Thus, this system reproduces
      early hematopoietic development in vitro and can serve as a model for analyzing
      the mechanisms of the globin switch in humans.

PMID- 16888281
TI  - Bone marrow transplantation attenuates the myopathic phenotype of a muscular
      mouse model of spinal muscular atrophy.
AB  - Bone marrow (BM) transplantation was performed on a muscular mouse model of
      spinal muscular atrophy that had been created by mutating the survival of motor
      neuron gene (Smn) in myofibers only. This model is characterized by a severe
      myopathy and progressive loss of muscle fibers leading to paralysis.
      Transplantation of wild-type BM cells following irradiation at a low dose (6 Gy)
      improved motor capacity (+85%). This correlated with a normalization of myofiber
      number associated with a higher number of regenerating myofibers (1.6-fold
      increase) and an activation of CD34 and Pax7 satellite cells. However, BM cells
      had a very limited capacity to replace or fuse to mutant myofibers (2%). These
      data suggest that BM transplantation was able to attenuate the myopathic
      phenotype through an improvement of skeletal muscle regeneration of recipient
      mutant mice, a process likely mediated by a biological activity of BM-derived
      cells. This hypothesis was further supported by the capacity of muscle protein
      extracts from transplanted mutant mice to promote myoblast proliferation in vitro
      (1.6-fold increase). In addition, a tremendous upregulation of hepatocyte growth
      factor (HGF), which activates quiescent satellite cells, was found in skeletal
      muscle of transplanted mutants compared with nontransplanted mutants. Eventually,
      thanks to the Cre-loxP system, we show that BM-derived muscle cells were strong
      candidates harboring this biological activity. Taken together, our data suggest
      that a biological activity is likely involved in muscle regeneration improvement
      mediated by BM transplantation. HGF may represent an attractive paracrine
      mechanism to support this activity.

PMID- 16888282
TI  - Isolation of multipotent neural crest-derived stem cells from the adult mouse
      cornea.
AB  - We report the presence of neural crest-derived corneal precursors (COPs) that
      initiate spheres by clonal expansion from a single cell. COPs expressed the stem
      cell markers nestin, Notch1, Musashi-1, and ABCG2 and showed the side population
      cell phenotype. COPs were multipotent with the ability to differentiate into
      adipocytes, chondrocytes, as well as neural cells, as shown by the expression of
      beta-III-tubulin, glial fibrillary acidic protein, and neurofilament-M. COP
      spheres prepared from E/nestin-enhanced green fluorescent protein (EGFP) mice
      showed induction of EGFP expression that was not originally observed in the
      cornea, indicating activation of the neural-specific nestin second intronic
      enhancer in culture. COPs were Sca-1(+), CD34(+), CD45(-), and c-kit(-). Numerous
      GFP(+) cells were observed in the corneas of mice transplanted with whole bone
      marrow of transgenic mice ubiquitously expressing GFP; however, no GFP(+) COP
      spheres were initiated from these mice. On the other hand, COP spheres from
      transgenic mice encoding P0-Cre/Floxed-EGFP as well as Wnt1-Cre/Floxed-EGFP were
      GFP(+), indicating the neural crest origin of COPs, which was confirmed by the
      expression of the embryonic neural crest markers Twist, Snail, Slug, and Sox9.
      Taken together, these data indicate the existence of neural crest-derived,
      multipotent stem cells in the adult cornea.

PMID- 16888283
TI  - Gut-like structures from mouse embryonic stem cells as an in vitro model for gut
      organogenesis preserving developmental potential after transplantation.
AB  - Recently, we reported the formation of gut-like structures from mouse ESCs in
      vitro. To determine whether ESCs provide an in vitro model of gastrointestinal
      (GI) tracts and their organogenesis, we investigated the morphological features,
      formation process, cellular development, and regional location within the GI
      tract by immunohistochemistry, electron microscopy, and reverse transcription
      polymerase chain reaction. We also examined the developmental potential by
      transplantation into kidney capsules. The results demonstrated that Id2
      expressing epithelium developed first, alpha-smooth muscle actin appeared around
      the periphery, and finally, the gut-like structures were formed into a three
      layer organ with well-differentiated epithelium. A connective tissue layer and
      musculature with interstitial cells of Cajal developed, similar to organogenesis
      of the embryonic gut. Enteric neurons appeared underdeveloped, and blood vessels
      were absent. Many structures expressed intestinal markers Cdx2 and 5
      hydroxytryptamine but not the stomach marker H(+)/K(+) ATPase. Transplants
      obtained blood vessels and extrinsic nerve growth from the host to prolong life,
      and even grafts of premature structures did not form teratoma. In conclusion, gut
      like structures were provided with prototypical tissue components of the GI tract
      and are inherent in the intestine rather than the stomach. The formation process
      was basically same as in gut organogenesis. They maintain their developmental
      potential after transplantation. Therefore, gut-like structures provide a unique
      and useful in vitro system for development and stem cell studies of the GI tract,
      including transplantation experiments.

PMID- 16888284
TI  - Endothelial differentiation potential of human monocyte-derived multipotential
      cells.
AB  - We previously reported a unique CD14(+)CD45(+)CD34(+) type I collagen(+) cell
      fraction derived from human circulating CD14(+) monocytes, named monocyte-derived
      multipotential cells (MOMCs). This primitive cell population contains progenitors
      capable of differentiating along the mesenchymal and neuronal lineages. Here, we
      investigated whether MOMCs can also differentiate along the endothelial lineage.
      MOMCs treated with angiogenic growth factors for 7 days changed morphologically
      and adopted a caudate appearance with rod-shaped microtubulated structures
      resembling Weibel-Palade bodies. Almost every cell expressed CD31, CD144,
      vascular endothelial growth factor (VEGF) type 1 and 2 receptors, Tie-2, von
      Willebrand factor (vWF), endothelial nitric-oxide synthase, and CD146, but
      CD14/CD45 expression was markedly downregulated. Under these culture conditions,
      the MOMCs continued to proliferate for up to 7 days. Functional characteristics,
      including vWF release upon histamine stimulation and upregulated expression of
      VEGF and VEGF type 1 receptor in response to hypoxia, were indistinguishable
      between the MOMC-derived endothelial-like cells and cultured mature endothelial
      cells. The MOMCs responded to angiogenic stimuli and promoted the formation of
      mature endothelial cell tubules in Matrigel cultures. Finally, in xenogenic
      transplantation studies using a severe combined immunodeficient mouse model,
      syngeneic colon carcinoma cells were injected subcutaneously with or without
      human MOMCs. Cotransplantation of the MOMCs promoted the formation of blood
      vessels, and more than 40% of the tumor vessel sections incorporated human
      endothelial cells derived from MOMCs. These findings indicate that human MOMCs
      can proliferate and differentiate along the endothelial lineage in a specific
      permissive environment and thus represent an autologous transplantable cell
      source for therapeutic neovasculogenesis.

PMID- 16888285
TI  - Notch signaling in stem cell systems.
AB  - The Notch signaling pathway is among the most commonly used communication
      channels in animal cells. Recent studies have demonstrated that this pathway is
      indispensable for cells in various stages of maturation, including terminal
      differentiation. One main focus in mammalian studies is the role of Notch in
      embryonic and postembryonic stem cell systems. In this review, the roles of Notch
      signaling in various mammalian stem and early progenitor cells are summarized.

PMID- 16888286
TI  - Cystic fibrosis mouse models.
AB  - Animal models of cystic fibrosis (CF) are powerful tools that enable the study of
      the mechanisms and complexities of human disease. Murine models have several
      intrinsic advantages compared with other animal models, including lower cost,
      maintenance, and rapid reproduction rate. Mice can be easily genetically
      manipulated by making transgenic or knockout mice, or by backcrossing to well
      defined inbred strains in a reasonably short period of time. However, anatomic
      and immunologic differences between mice and humans mean that murine models have
      inherent limitations that must be considered when interpreting the results
      obtained from experimental models and applying these to the pathogenesis of CF
      disease in humans. This review will focus on the different CF mouse models
      available that represent diverse phenotypes observed in humans with CF and that
      can help researchers elucidate the diverse functions of the CFTR protein.

PMID- 16888288
TI  - Alveolar cell senescence in patients with pulmonary emphysema.
AB  - RATIONALE AND OBJECTIVES: The prevalence of chronic obstructive pulmonary disease
      (COPD) is age-dependent, suggesting an intimate relationship between the
      pathogenesis of COPD and aging. In this study we investigated whether the
      senescence of alveolar epithelial and endothelial cells is accelerated in
      emphysematous lungs. METHODS: Samples of lung tissue were obtained from patients
      with emphysema, asymptomatic smokers, and asymptomatic nonsmokers. Paraffin
      embedded lung tissue sections were evaluated for cellular senescence by
      quantitative fluorescence in situ hybridization to assess telomere shortening,
      and by immunohistochemistry to assess the expression of senescence-associated
      cyclin-dependent kinase inhibitors. Tissue sections were also immunostained for
      proliferating cell nuclear antigen (PCNA), surfactant protein A, and CD31. MAIN
      RESULTS: The patients with emphysema had significantly higher percentages of type
      II cells positive for p16INK4a and p21CIP1/WAF1/Sdi1 than the asymptomatic
      smokers and nonsmokers. They had also significantly higher percentages of
      endothelial cells positive for p16INK4a than the asymptomatic smokers and
      nonsmokers, and higher percentages of endothelial cells positive for
      p21CIP1/WAF1/Sdi1 than the asymptomatic nonsmokers. Telomere length in alveolar
      type II cells and endothelial cells was significantly shorter in the patients
      with emphysema than in the asymptomatic nonsmokers. The level of p16INK4a
      expression was negatively correlated with the level of PCNA expression. The level
      of alveolar cell senescence was positively correlated with airflow limitation.
      CONCLUSIONS: These results suggest that the senescence of alveolar epithelial and
      endothelial cells is accelerated in patients with emphysema. Cellular senescence
      may explain the abnormal cell turnover that promotes the loss of alveolar cells
      in emphysematous lungs.

PMID- 16888287
TI  - IL-1beta disrupts postnatal lung morphogenesis in the mouse.
AB  - Pulmonary inflammation and increased production of the inflammatory cytokine IL
      1beta are associated with the development of bronchopulmonary dysplasia (BPD) in
      premature infants. To study the actions of IL-1beta in the fetal and newborn lung
      in vivo, we developed a bitransgenic mouse in which IL-1beta is expressed under
      conditional control in airway epithelial cells. Perinatal pulmonary expression of
      IL-1beta caused respiratory insufficiency that was associated with increased
      postnatal mortality. While intrauterine growth of IL-1beta-expressing mice was
      normal, their postnatal growth was impaired. IL-1beta disrupted alveolar
      septation and caused abnormalities in alpha-smooth muscle actin and elastin
      deposition in the septa of distal airspaces. IL-1beta disturbed capillary
      development and inhibited the production of vascular endothelial growth factor in
      the lungs of infant mice. IL-1beta induced the expression of CXC chemokines KC
      (CXCL1) and macrophage inflammatory protein-2 (CXCL2) and of CC chemokines
      monocyte chemotactic protein (MCP)-1 (CCL2) and MCP-3 (CCL7), consistent with
      neutrophilic and monocytic infiltration of the lungs. IL-1beta caused goblet cell
      metaplasia and bronchial smooth muscle hyperplasia. Perinatal expression of IL
      1beta in epithelial cells of the lung caused a lung disease that was clinically
      and histologically similar to BPD.

PMID- 16888289
TI  - Tricuspid annular displacement predicts survival in pulmonary hypertension.
AB  - RATIONALE: Right ventricular (RV) function is an important determinant of
      prognosis in pulmonary hypertension. However, noninvasive assessment of the RV
      function is often limited by complex geometry and poor endocardial definition.
      OBJECTIVES: To test whether the degree of tricuspid annular displacement
      (tricuspid annular plane systolic excursion [TAPSE]) is a useful echo-derived
      measure of RV function with prognostic significance in pulmonary hypertension.
      METHODS: We prospectively studied 63 consecutive patients with pulmonary
      hypertension who were referred for a clinically indicated right heart
      catheterization. Patients underwent right heart catheterization immediately
      followed by transthoracic echocardiogram and TAPSE measurement. RESULTS: In the
      overall cohort, a TAPSE of less than 1.8 cm was associated with greater RV
      systolic dysfunction (cardiac index, 1.9 vs. 2.7 L/min/m2; RV % area change, 24
      vs. 33%), right heart remodeling (right atrial area index, 17.0 vs. 12.1
      cm(2)/m), and RV-left ventricular (LV) disproportion (RV/LV diastolic area, 1.7
      vs. 1.2; all p < 0.001), versus a TAPSE of 1.8 cm or greater. In patients with
      pulmonary arterial hypertension (PAH; n = 47), survival estimates at 1 and 2 yr
      were 94 and 88%, respectively, in those with a TAPSE of 1.8 cm or greater versus
      60 and 50%, respectively, in subjects with a TAPSE less than 1.8 cm. The
      unadjusted risk of death (hazard ratio) in patients with a TAPSE less than 1.8
      versus 1.8 cm or greater was 5.7 (95% confidence interval, 1.3-24.9; p = 0.02)
      for the PAH cohort. For every 1-mm decrease in TAPSE, the unadjusted risk of
      death increased by 17% (hazard ratio, 1.17; 95% confidence interval, 1.05-1.30; p
      = 0.006), which persisted after adjusting for other echocardiographic and
      hemodynamic variables and baseline treatment status. CONCLUSIONS: TAPSE
      powerfully reflects RV function and prognosis in PAH.

PMID- 16888290
TI  - Congenital central hypoventilation syndrome: PHOX2B mutations and phenotype.
AB  - RATIONALE: Congenital central hypoventilation syndrome (CCHS), a unique disorder
      of respiratory control associated with Hirschsprung disease (HSCR) and tumors of
      neural crest origin, results from polyalanine repeat expansion mutations in the
      paired-like homeobox (PHOX)2B gene in more than 90% of cases, and alternative
      PHOX2B mutations in remaining cases. OBJECTIVES: To characterize CCHS-associated
      nonpolyalanine repeat mutations in PHOX2B, evaluate genotype-phenotype
      relationships, and compare clinical features of CCHS in cases with nonpolyalanine
      repeat mutations to those with polyalanine expansion mutations. METHODS: DNA from
      probands was analyzed by polymerase chain reaction for the common polyalanine
      repeat expansion. If no expansion was present, coding regions and intron-exon
      boundaries of PHOX2B were sequenced. When possible, parents and siblings were
      screened for the mutation found in the proband. RESULTS: Fourteen nonpolyalanine
      repeat mutations, including missense, nonsense, and frameshift mutations, and 170
      polyalanine repeat mutations were identified in 184 CCHS probands. Both
      incomplete penetrance and parental mosaicism were observed within the family
      members of probands with nonpolyalanine repeat mutations. Increased prevalence of
      continuous ventilatory dependence, HSCR, and neural crest tumors was seen in the
      nonpolyalanine repeat group compared to those with polyalanine repeat mutations.
      CONCLUSIONS: These data suggest that nonpolyalanine repeat mutations produce more
      severe disruption of PHOX2B function. Patients carrying these mutations should be
      evaluated for HSCR and neural crest tumors. Because incomplete penetrance can
      occur in families of CCHS probands with PHOX2B mutations, genetic screening of
      appropriate family members is indicated to evaluate reproductive risk and because
      asymptomatic mutation carriers may be at risk for developing alveolar
      hypoventilation.

PMID- 16888291
TI  - Surveillance and management of all types of Staphylococcus aureus bacteraemia.

PMID- 16888292
TI  - Further lessons from the TGN1412 tragedy.

PMID- 16888293
TI  - What to tell patients about radioiodine therapy.

PMID- 16888294
TI  - Classification of illegal and harmful drugs.

PMID- 16888295
TI  - Measuring disparities in health care.

PMID- 16888296
TI  - Changes to death certificates waste golden opportunity.

PMID- 16888297
TI  - Tobacco and alcohol should be classed as dangerous drugs.

PMID- 16888298
TI  - Doctor struck off after vaccines scandal.

PMID- 16888299
TI  - Rules for drug trials should be tightened, say experts.

PMID- 16888300
TI  - US journal in row over sponsored supplement.

PMID- 16888301
TI  - Humanitarian aid corridor fails to materialise.

PMID- 16888302
TI  - Drug industry told to disclose details of doctors' events.

PMID- 16888303
TI  - Two Albanians die from black widow spider bites.

PMID- 16888304
TI  - FDA to clarify rules on advisory committee members.

PMID- 16888305
TI  - Varicose veins and their management.

PMID- 16888306
TI  - Triggering radiation alarms after radioiodine treatment.

PMID- 16888308
TI  - Overcoming barriers to recruitment in health research.

PMID- 16888309
TI  - Regulation and revalidation of doctors: summary of other responses.

PMID- 16888310
TI  - Regulation and revalidation of doctors: dangers and opportunities.

PMID- 16888311
TI  - Regulation and revalidation of doctors: response from the General Medical
      Council.

PMID- 16888312
TI  - Stirrups or no stirrups for routine speculum examinations? Patient comfort is
      secondary to cervical smear quality...

PMID- 16888314
TI  - Is public health action worth while if many cases are being missed?

PMID- 16888313
TI  - Why do poor outcomes persist in diabetic pregnancy?

PMID- 16888315
TI  - Minerva might help you get something published.

PMID- 16888316
TI  - Doctors and patients need to hunt together.

PMID- 16888317
TI  - Stirrups or no stirrups for routine speculum examinations? Patient's perspective.

PMID- 16888318
TI  - Stirrups or no stirrups for routine speculum examinations? ...but we do not need
      to do a trial of smear quality.

PMID- 16888319
TI  - Protective effect of apolipoprotein E2 on coronary artery disease in African
      Americans is mediated through lipoprotein cholesterol.
AB  - We studied the relationship of apolipoprotein E (apoE) isoforms and coronary
      artery disease (CAD) in 224 African Americans and 326 Caucasians undergoing
      diagnostic coronary angiography. The presence of CAD was defined as >50% stenosis
      in at least one artery. ApoE allele frequencies were 0.12, 0.62, and 0.26 for
      epsilon 2, epsilon 3, and epsilon 4, respectively, in African Americans and 0.08,
      0.78, and 0.14 for epsilon 2, epsilon 3, and epsilon 4, respectively, in
      Caucasians. Among African Americans, CAD was present in 9 of 34 epsilon 2
      carriers (26%), significantly smaller (P < 0.05) in proportion compared with 39
      of 82 epsilon 3 carriers and 43 of 92 epsilon 4 carriers (48% and 47%,
      respectively), suggesting a protective effect of the epsilon 2 allele. No such
      difference was seen in Caucasians. In African Americans but not Caucasians, LDL
      cholesterol was lower in epsilon 2 carriers than in epsilon 3 and epsilon 4
      carriers (106 vs. 127 and 134 mg/dl, respectively; P < 0.005). After adjusting
      for lipid levels, the association between apoE2 and CAD was no longer
      significant. Thus, the protective effect of apoE2 seen in African Americans could
      be explained by a favorable lipid profile in epsilon 2 carriers, whereas in
      Caucasians, the absence of such a protective effect could be attributable to the
      lack of effect of apoE2 on the lipid profile.

PMID- 16888320
TI  - Autoantibody titers against OxLDL are correlated with Achilles tendon thickness
      in patients with familial hypercholesterolemia.
AB  - Achilles tendon xanthomas are associated with increased cardiovascular risk in
      patients with familial hypercholesterolemia (FH). Oxidized low density
      lipoprotein (OxLDL), the antibodies against OxLDL, and the LDL-associated
      phospholipase A(2) (Lp-PLA(2)) may play important roles in atherogenesis. We
      investigated the possible association between plasma levels of OxLDL, Lp-PLA(2)
      activity, and autoantibody titers against various types of mildly OxLDL with
      Achilles tendon thickness (ATT). ATT was determined by sonography in 80 unrelated
      heterozygous FH patients. Three different types of mildly OxLDL were prepared:
      OxLDL(L), OxLDL(P), and OxLDL(D), at the end of the lag, propagation, and
      decomposition phases of oxidation, respectively. Similar types of OxLDL were also
      prepared after inactivation of the LDL-associated Lp-PLA(2). These types were
      denoted OxLDL(-)(L), OxLDL(-)(P), and OxLDL(-)(D). FH patients exhibited
      significantly higher plasma OxLDL levels and serum IgG titers against OxLDL(P)
      and OxLDL(D) compared with 40 normolipidemic apparently healthy controls. ATT
      values were positively correlated with autoantibody titers against OxLDL(P) and
      OxLDL(D); however, in multiple regression analysis, ATT was independently
      associated only with the autoantibody titers against OxLDL(D). We conclude that
      the IgG autoantibody titers against OxLDL(D) but not OxLDL or Lp-PLA(2) may play
      an important role in the pathogenesis of Achilles tendon xanthomas in FH
      patients.

PMID- 16888321
TI  - A microRNA detection system based on padlock probes and rolling circle
      amplification.
AB  - The differential expression and the regulatory roles of microRNAs (miRNAs) are
      being studied intensively these years. Their minute size of only 19-24
      nucleotides and strong sequence similarity among related species call for
      enhanced methods for reliable detection and quantification. Moreover, miRNA
      expression is generally restricted to a limited number of specific cells within
      an organism and therefore requires highly sensitive detection methods. Here we
      present a simple and reliable miRNA detection protocol based on padlock probes
      and rolling circle amplification. It can be performed without specialized
      equipment and is capable of measuring the content of specific miRNAs in a few
      nanograms of total RNA.

PMID- 16888322
TI  - RNA aptamers selectively modulate protein recruitment to the cytoplasmic domain
      of beta-secretase BACE1 in vitro.
AB  - The beta-amyloid peptide (Abeta) is a major component of the Alzheimer's disease
      (AD)-associated senile plaques and is generated by sequential cleavage of the
      beta-amyloid precursor protein (APP) by beta-secretase and gamma-secretase. Since
      BACE1 initiates Abeta generation it represents a valuable target to interfere
      with Abeta production and treatment of AD. While the enzymatic activity of BACE1
      resides in the extracellular domain, the protein also contains a short
      cytoplasmic tail (B1-CT). This domain serves as a binding site for at least two
      proteins, the copper chaperone for superoxide dismutase-1 (CCS), and the Golgi
      localized, gamma-ear-containing, ADP ribosylation factor-binding (GGA1) protein,
      and contains a single phosphorylation site. However, the precise role of the B1
      CT for the overall biological function of this protein is largely unknown.
      Functional studies focusing on the activity of this domain would strongly benefit
      from the availability of domain-specific inhibitors. Here we describe the
      isolation and characterization of RNA aptamers that selectively target the B1-CT.
      We show that these RNAs bind to authentic BACE1 and provide evidence that the
      binding site is restricted to the membrane-proximal half of the C terminus.
      Aptamer-binding specifically interferes with the recruitment of CCS, but still
      permits GGA1 association and casein kinase-dependent phosphorylation, consistent
      with selective binding site targeting within this short peptide. Because
      phosphorylation and GGA1 binding to B1-CT regulate BACE1 transport, these RNA
      inhibitors could be applied to investigate B1-CT activity without affecting the
      subcellular localization of BACE1.

PMID- 16888323
TI  - MicroRNA promoter element discovery in Arabidopsis.
AB  - In this study we present a method of identifying Arabidopsis miRNA promoter
      elements using known transcription factor binding motifs. We provide a
      comparative analysis of the representation of these elements in miRNA promoters,
      protein-coding gene promoters, and random genomic sequences. We report five
      transcription factor (TF) binding motifs that show evidence of overrepresentation
      in miRNA promoter regions relative to the promoter regions of protein-coding
      genes. This investigation is based on the analysis of 800-nucleotide regions
      upstream of 63 experimentally verified Transcription Start Sites (TSS) for miRNA
      primary transcripts in Arabidopsis. While the TATA-box binding motif was also
      previously reported by Xie and colleagues, the transcription factors AtMYC2, ARF,
      SORLREP3, and LFY are identified for the first time as overrepresented binding
      motifs in miRNA promoters.

PMID- 16888324
TI  - Pokeweed antiviral protein depurinates the sarcin/ricin loop of the rRNA prior to
      binding of aminoacyl-tRNA to the ribosomal A-site.
AB  - Ribosome-inactivating proteins, such as the pokeweed antiviral protein (PAP),
      inhibit translation by depurinating the conserved sarcin/ricin loop of the large
      ribosomal RNA. Depurinated ribosomes are unable to bind elongation factor 2, and,
      thus, the translocation step of the elongation cycle is inhibited. Though the
      consequences of depurination are well characterized, the ribosome conformation
      required for depurination to take place has not been described. In this report,
      we correlate biochemical and genetic data to conclude that pokeweed antiviral
      protein depurinates the sarcin/ricin loop when the A-site of the ribosomal
      peptidyl-transferase center is unoccupied. We show that prior incubation of
      ribosomes with puromycin, an analog of the 3'-terminus of aminoacyl-tRNA,
      inhibits both binding and depurination by PAP in a concentration-dependent
      manner. Expression of PAP in the yeast strain mak8-1 results in little
      depurination unless the cells are lysed, a process that would promote loss of
      aminoacyl-tRNA from the ribosome. The mak8-1 strain is known to exhibit a higher
      affinity for aminoacyl-tRNA compared with wild-type cells, and therefore, its
      ribosomes are more resistant to PAP in vivo. These data contribute to the
      mechanism of action of pokeweed antiviral protein; specifically, they have
      uncovered the ribosomal conformation required for depurination that leads to
      subsequent translation inhibition.

PMID- 16888325
TI  - The drosophila fragile X protein dFMR1 is required during early embryogenesis for
      pole cell formation and rapid nuclear division cycles.
AB  - The FMR family of KH domain RNA-binding proteins is conserved from invertebrates
      to humans. In humans, inactivation of the X-linked FMR gene fragile X is the most
      common cause of mental retardation and leads to defects in neuronal architecture.
      While there are three FMR family members in humans, there is only a single gene,
      dfmr1, in flies. As in humans, inactivation of dfmr1 causes defects in neuronal
      architecture and in behavior. dfmr1 has other functions in the fly in addition to
      neurogenesis. Here we have analyzed its role during early embryonic development.
      We found that dfmr1 embryos display defects in the rapid nuclear division cycles
      that precede gastrulation in nuclear migration and in pole cell formation. While
      the aberrations in nuclear division are correlated with a defect in the assembly
      of centromeric/centric heterochromatin, the defects in pole cell formation are
      associated with alterations in the actin-myosin cytoskeleton.

PMID- 16888327
TI  - Genomewide expression profiling in the zebrafish embryo identifies target genes
      regulated by Hedgehog signaling during vertebrate development.
AB  - Hedgehog proteins play critical roles in organizing the embryonic development of
      animals, largely through modulation of target gene expression. Little is
      currently known, however, about the kinds and numbers of genes whose expression
      is controlled, directly or indirectly, by Hedgehog activity. Using techniques to
      globally repress or activate Hedgehog signaling in zebrafish embryos followed by
      microarray-based expression profiling, we have discovered a cohort of genes whose
      expression responds significantly to loss or gain of Hedgehog function. We have
      confirmed the Hedgehog responsiveness of a representative set of these genes with
      whole-mount in situ hybridization as well as real time PCR. In addition, we show
      that the consensus Gli-binding motif is enriched within the putative regulatory
      elements of a sizeable proportion of genes that showed positive regulation in our
      assay, indicating that their expression is directly induced by Hedgehog. Finally,
      we provide evidence that the Hedgehog-dependent spatially restricted
      transcription of one such gene, nkx2.9, is indeed mediated by Gli1 through a
      single Gli recognition site located within an evolutionarily conserved enhancer
      fragment. Taken together, this study represents the first comprehensive survey of
      target genes regulated by the Hedgehog pathway during vertebrate development. Our
      data also demonstrate for the first time the functionality of the Gli-binding
      motif in the control of Hedgehog signaling-induced gene expression in the
      zebrafish embryo.

PMID- 16888326
TI  - Ltv1 is required for efficient nuclear export of the ribosomal small subunit in
      Saccharomyces cerevisiae.
AB  - In eukaryotes, 40S and 60S ribosomal subunits are assembled in the nucleus and
      exported to the cytoplasm independently of one another. Nuclear export of the 60S
      requires the adapter protein Nmd3, but no analogous adapter has been identified
      for the 40S. Ltv1 is a nonessential, nonribosomal protein that is required for
      40S subunit biogenesis in yeast. Cells lacking LTV1 grow slowly, are
      hypersensitive to inhibitors of protein synthesis, and produce about half as many
      40S subunits as do wild-type cells. Ltv1 interacts with Crm1, co-sediments in
      sucrose gradients with 43S/40S subunits, and copurifies with late 43S particles.
      Here we show that Ltv1 shuttles between nucleus and cytoplasm in a Crm1-dependent
      manner and that it contains a functional NES that is sufficient to direct the
      export of an NLS-containing reporter. Small subunit export is reduced in
      Deltaltv1 mutants, as judged by the altered distribution of the 5'-ITS1 rRNA and
      the 40S ribosomal protein RpS3. Finally, we show a genetic interaction between
      LTV1 and YRB2, a gene that encodes a Ran-GTP-, Crm1-binding protein that
      facilitates the small subunit export. We propose that Ltv1 functions as one of
      several possible adapter proteins that link the nuclear export machinery to the
      small subunit.

PMID- 16888328
TI  - Cumulative effects of spontaneous mutations for fitness in Caenorhabditis: role
      of genotype, environment and stress.
AB  - It is often assumed that the mutation rate is an evolutionarily optimized
      property of a taxon. The relevant mutation rate is for mutations that affect
      fitness, U, but the strength of selection on the mutation rate depends on the
      average effect of a mutation. Determination of U is complicated by the
      possibility that mutational effects depend on the particular environmental
      context in which the organism exists. It has been suggested that the effects of
      deleterious mutations are typically magnified in stressful environments, but most
      studies confound genotype with environment, so it is unclear to what extent
      environmental specificity of mutations is specific to a particular starting
      genotype. We report a study designed to separate effects of species, genotype,
      and environment on the degradation of fitness resulting from new mutations.
      Mutations accumulated for >200 generations at 20 degrees in two strains of two
      species of nematodes that differ in thermal sensitivity. Caenorhabditis briggsae
      and C. elegans have similar demography at 20 degrees, but C. elegans suffers
      markedly reduced fitness at 25 degrees. We find little evidence that mutational
      properties differ depending on environmental conditions and mutational
      correlations between environments are close to those expected if effects were
      identical in both environments.

PMID- 16888330
TI  - The fate of transposable elements in asexual populations.
AB  - Sexual reproduction and recombination are important for maintaining a stable copy
      number of transposable elements (TEs). In sexual populations, elements can be
      contained by purifying selection against host carriers with higher element copy
      numbers; however, in the absence of sex and recombination, asexual populations
      could be driven to extinction by an unchecked proliferation of TEs. Here we
      provide a theoretical framework for analyzing TE dynamics under asexual
      reproduction. Analytic results show that, in an infinite asexual population, an
      equilibrium in copy number is achieved if no element excision is possible, but
      that all TEs are eliminated if there is some excision. In a finite population,
      computer simulations demonstrate that small populations are driven to extinction
      by a Muller's ratchet-like process of element accumulation, but that large
      populations can be cured of vertically transmitted TEs, even with excision rates
      well below transposition rates. These results may have important consequences for
      newly arisen asexual lineages and may account for the lack of deleterious
      retrotransposons in the putatively ancient asexual bdelloid rotifers.

PMID- 16888329
TI  - Repair of DNA damage induced by bile salts in Salmonella enterica.
AB  - Exposure of Salmonella enterica to sodium cholate, sodium deoxycholate, sodium
      chenodeoxycholate, sodium glycocholate, sodium taurocholate, or sodium
      glycochenodeoxycholate induces the SOS response, indicating that the DNA-damaging
      activity of bile resides in bile salts. Bile increases the frequency of GC --> AT
      transitions and induces the expression of genes belonging to the OxyR and SoxRS
      regulons, suggesting that bile salts may cause oxidative DNA damage. S. enterica
      mutants lacking both exonuclease III (XthA) and endonuclease IV (Nfo) are bile
      sensitive, indicating that S. enterica requires base excision repair (BER) to
      overcome DNA damage caused by bile salts. Bile resistance also requires DinB
      polymerase, suggesting the need of SOS-associated translesion DNA synthesis.
      Certain recombination functions are also required for bile resistance, and a key
      factor is the RecBCD enzyme. The extreme bile sensitivity of RecB-, RecC-, and
      RecA- RecD- mutants provides evidence that bile-induced damage may impair DNA
      replication.

PMID- 16888331
TI  - The genetic architecture of life span and mortality rates: gender and species
      differences in inbreeding load of two seed-feeding beetles.
AB  - We examine the inbreeding load for adult life span and mortality rates of two
      seed beetle species, Callosobruchus maculatus and Stator limbatus. Inbreeding
      load differs substantially between males and females in both study populations of
      C. maculatus--life span of inbred females was 9-13% shorter than the life span of
      outbred females, whereas the life span of inbred males did not differ from the
      life span of outbred males. The effect of inbreeding on female life span was
      largely due to an increase in the slope of the mortality curve. In contrast,
      inbreeding had only a small effect on the life span of S. limbatus--life spans of
      inbred beetles were approximately 5% shorter than those of outbred beetles, and
      there was no difference in inbreeding load between the sexes. The inbreeding load
      for mean life span was approximately 0.4-0.6 lethal equivalents per haploid
      gamete for female C. maculatus and approximately 0.2-0.3 for both males and
      females of S. limbatus, all within the range of estimates commonly obtained for
      Drosophila. However, contrary to the predictions of mutation-accumulation models,
      inbreeding load for loci affecting mortality rates did not increase with age in
      either species, despite an effect of inbreeding on the initial rate of increase
      in mortality. This was because mortality rates decelerated with age and converged
      to a mortality plateau for both outbred and inbred beetles.

PMID- 16888332
TI  - Inheritance patterns of transcript levels in F1 hybrid mice.
AB  - Genetic analysis of transcriptional regulation is a rapidly emerging field of
      investigation that promises to shed light on the regulatory networks that control
      gene expression. Although a number of such studies have been carried out, the
      nature and extent of the heritability of gene expression traits have not been
      well established. We describe the inheritance of transcript levels in liver
      tissue in the first filial (F1) generation of mice obtained from reciprocal
      crosses between the common inbred strains A/J and C57BL/6J. We obtain estimates
      of genetic and technical variance components from these data and demonstrate that
      shrinkage estimators can increase detectable heritability. Estimates of
      heritability vary widely from transcript to transcript, with one-third of
      transcripts showing essentially no heritability (<0.01) and one-quarter showing
      very high heritability (>0.50). Roughly half of all transcripts are
      differentially expressed between the two parental strains. Most transcripts show
      an additive pattern of inheritance. Dominance effects were observed for 20% of
      transcripts and a small number of transcripts were identified as showing an
      overdominance mode of inheritance. In addition, we identified 314 transcripts
      with expression levels that differ between the reciprocal F1 animals. These genes
      may be related to maternal effect.

PMID- 16888333
TI  - Genetic and environmental effects on complex traits in mice.
AB  - The interaction between genotype and environment is recognized as an important
      source of experimental variation when complex traits are measured in the mouse,
      but the magnitude of that interaction has not often been measured. From a study
      of 2448 genetically heterogeneous mice, we report the heritability of 88 complex
      traits that include models of human disease (asthma, type 2 diabetes mellitus,
      obesity, and anxiety) as well as immunological, biochemical, and hematological
      phenotypes. We show that environmental and physiological covariates are involved
      in an unexpectedly large number of significant interactions with genetic
      background. The 15 covariates we examined have a significant effect on behavioral
      and physiological tests, although they rarely explain >10% of the variation. We
      found that interaction effects are more frequent and larger than the main
      effects: half of the interactions explained >20% of the variance and in nine
      cases exceeded 50%. Our results indicate that assays of gene function using mouse
      models should take into account interactions between gene and environment.

PMID- 16888334
TI  - Bayesian clustering using hidden Markov random fields in spatial population
      genetics.
AB  - We introduce a new Bayesian clustering algorithm for studying population
      structure using individually geo-referenced multilocus data sets. The algorithm
      is based on the concept of hidden Markov random field, which models the spatial
      dependencies at the cluster membership level. We argue that (i) a Markov chain
      Monte Carlo procedure can implement the algorithm efficiently, (ii) it can detect
      significant geographical discontinuities in allele frequencies and regulate the
      number of clusters, (iii) it can check whether the clusters obtained without the
      use of spatial priors are robust to the hypothesis of discontinuous geographical
      variation in allele frequencies, and (iv) it can reduce the number of loci
      required to obtain accurate assignments. We illustrate and discuss the
      implementation issues with the Scandinavian brown bear and the human CEPH
      diversity panel data set.

PMID- 16888335
TI  - Assessing the significance of quantitative trait loci in replicable mapping
      populations.
AB  - Replicable populations, such as panels of recombinant inbred or doubled haploid
      lines, are convenient resources for the mapping of QTL. To increase mapping
      power, replications are often collected within each RI line and a common way to
      analyze such data is to include in the QTL model only a single measurement from
      each line that represents the average among the replicates (a line means model).
      An obvious, but seldom explored, alternative, is to include every replicate in
      the model (a full data model). Here, we use simulations to compare these two
      approaches. Further, we propose an extension of the standard permutation
      procedure that is required to correctly control the type I error in mapping
      populations with nested structure.

PMID- 16888336
TI  - Zebrafish genomic instability mutants and cancer susceptibility.
AB  - Somatic loss of tumor suppressor gene function comprising the second hit of
      Knudson's two-hit hypothesis is important in human cancer. A genetic screen was
      performed in zebrafish (Danio rerio) to find mutations that cause genomic
      instability (gin), as scored by Streisinger's mosaic-eye assay that models this
      second hit. The assay, based on a visible test for loss of wild-type gene
      function at a single locus, golden, is representative of genomewide events.
      Twelve ENU-induced genomic instability (gin) mutations were isolated. Most
      mutations showed weak dominance in heterozygotes and all showed a stronger
      phenotype in homozygotes. Trans-heterozygosity for 7 of these mutations showed
      greatly enhanced instability. A variety of spontaneous tumors were found in
      heterozygous adults from all gin lines, consistent with the expectation that
      genomic instability (mutator) mutations can accelerate carcinogenesis. The
      incidence of spontaneous cancer at 30-34 months was increased 9.6-fold in
      heterozygotes for the mutant with the strongest phenotype, gin-10. Tumors were
      seen in skin, colon, kidney, liver, pancreas, ovary, testis, and neuronal
      tissues, with multiple tumors in some fish. The study of these mutants will add
      to our understanding of the mechanisms of somatic loss of gene function and how
      those mechanisms contribute to cancer susceptibility.

PMID- 16888337
TI  - Variable populations within variable populations: quantifying mitochondrial
      heteroplasmy in natural populations of the gynodioecious plant Silene vulgaris.
AB  - Populations of mitochondria reside within individuals. Among angiosperms, these
      populations are rarely considered as genetically variable entities and typically
      are not found to be heteroplasmic in nature, leading to the widespread assumption
      that plant mitochondrial populations are homoplasmic. However, empirical studies
      of mitochondrial variation in angiosperms are relatively uncommon due to a
      paucity of sequence variation. Recent greenhouse studies of Silene vulgaris
      suggested that heteroplasmy might occur in this species at a level that it is
      biologically relevant. Here, we use established qualitative methods and a novel
      quantitative PCR method to study the intraindividual population genetics of
      mitochondria across two generations in natural populations of S. vulgaris. We
      show incidences of heteroplasmy for mitochondrial atpA and patterns of
      inheritance that are suggestive of more widespread heteroplasmy at both atpA and
      cox1. Further, our results demonstrate that quantitative levels of mitochondrial
      variation within individuals are high, constituting 26% of the total in one
      population. These findings are most consistent with a biparental model of
      mitochondrial inheritance. However, selection within individuals may be
      instrumental in the maintenance of variation because S. vulgaris is
      gynodioecious. Male sterility is, in part, regulated by the mitochondrial genome,
      and strong selection pressures appear to influence the frequency of females in
      these populations.

PMID- 16888338
TI  - Drosophila mus301/spindle-C encodes a helicase with an essential role in double
      strand DNA break repair and meiotic progression.
AB  - mus301 was identified independently in two genetic screens, one for mutants
      hypersensitive to chemical mutagens and another for maternal mutants with
      eggshell defects. mus301 is required for the proper specification of the oocyte
      and for progression through meiosis in the Drosophila ovary. We have cloned
      mus301 and show that it is a member of the Mus308 subfamily of ATP-dependent
      helicases and the closest homolog of human and mouse HEL308. Functional analyses
      demonstrate that Mus301 is involved in chromosome segregation in meiosis and in
      the repair of double-strand-DNA breaks in both meiotic and mitotic cells. Most of
      the oogenesis defects of mus301 mutants are suppressed by mutants in the
      checkpoint kinase Mei41 and in MeiW68, the Spo11 homolog that is thought to
      generate the dsDNA breaks that initiate recombination, indicating that these
      phenotypes are caused by activation of the DNA damage checkpoint in response to
      unrepaired Mei-W68-induced dsDNA breaks. However, neither mei-W68 nor mei-41
      rescue the defects in oocyte specification of mus301 mutants, suggesting that
      this helicase has another function in oocyte selection that is independent from
      its role in meiotic recombination.

PMID- 16888339
TI  - Marker genotypes and population admixture and their association with body weight,
      height and relative body mass in United States federal bison herds.
AB  - Elucidating genetic influences on bison growth and body composition is of
      interest, not only because bison are important for historical, cultural, and
      agricultural reasons, but also because their unusual population history makes
      them valuable models for finding influential loci in both domestic cattle and
      humans. We tested for trait loci associated with body weight, height, and bison
      mass index (BMI) while controlling for estimated ancestry to reduce potential
      confounding effects due to population admixture in 1316 bison sampled from four
      U.S. herds. We used 60 microsatellite markers to model each phenotype as a
      function of herd, sex, age, marker genotypes, and individual ancestry estimates.
      Statistical significance for genotype and its interaction with ancestry was
      evaluated using the adaptive false discovery rate. Of the four herds, two
      appeared to be admixed and two were nonadmixed. Although none of the main effects
      of the loci were significant, estimated ancestry and its interaction with marker
      loci were significantly associated with the phenotypes, illustrating the
      importance of including ancestry in the models and the dependence of genotype
      phenotype associations on background ancestry. Individual loci contributed
      approximately 2.0% of variation in weight, height, and BMI, which confirms the
      utility and potential importance of adjusting for population stratification.

PMID- 16888341
TI  - Marker-based prediction of the parental genome contribution to inbred lines
      derived from biparental crosses.
AB  - Molecular markers can be employed to predict the parental genome contribution to
      inbred lines. The proportion alpha of alleles originating from parent P1 at
      markers polymorphic between the parental lines P1 and P2 is commonly used as a
      predictor for the genome contribution of parent P1 to an offspring line. Our
      objectives were to develop a new marker-based predictor xi for the parental
      genome contribution, which takes into account not only the alleles at marker loci
      but also their map distance, and to compare the prediction precision of xi with
      that of alternative methods. We derived formulas for xi for inbreds derived from
      biparental crosses (F1 and backcrosses) with the single-seed descent or double
      haploid method and presented an extension xi* possessing statistical optimum
      properties. In a simulation study, alpha showed a systematic overestimation of
      large parental genome contribution that was not observed for xi. The mean squared
      prediction error of xi was at least 50% smaller than that of alpha for linkage
      maps with unequal distances between adjacent markers. A data set from a study on
      plant variety protection in maize was used to illustrate the application of xi.
      We conclude that xi provides substantially greater prediction precision than the
      commonly used predictor alpha in a broad range of applications in genetics and
      breeding.

PMID- 16888340
TI  - Design of microarray experiments for genetical genomics studies.
AB  - Microarray experiments have been used recently in genetical genomics studies, as
      an additional tool to understand the genetic mechanisms governing variation in
      complex traits, such as for estimating heritabilities of mRNA transcript
      abundances, for mapping expression quantitative trait loci, and for inferring
      regulatory networks controlling gene expression. Several articles on the design
      of microarray experiments discuss situations in which treatment effects are
      assumed fixed and without any structure. In the case of two-color microarray
      platforms, several authors have studied reference and circular designs. Here, we
      discuss the optimal design of microarray experiments whose goals refer to
      specific genetic questions. Some examples are used to illustrate the choice of a
      design for comparing fixed, structured treatments, such as genotypic groups.
      Experiments targeting single genes or chromosomic regions (such as with transgene
      research) or multiple epistatic loci (such as within a selective phenotyping
      context) are discussed. In addition, microarray experiments in which treatments
      refer to families or to subjects (within family structures or complex pedigrees)
      are presented. In these cases treatments are more appropriately considered to be
      random effects, with specific covariance structures, in which the genetic goals
      relate to the estimation of genetic variances and the heritability of
      transcriptional abundances.

PMID- 16888343
TI  - Sequence conservation of homeologous bacterial artificial chromosomes and
      transcription of homeologous genes in soybean (Glycine max L. Merr.).
AB  - The paleopolyploid soybean genome was investigated by sequencing homeologous BAC
      clones anchored by duplicate N-hydroxycinnamoyl/benzoyltransferase (HCBT) genes.
      The homeologous BACs were genetically mapped to linkage groups C1 and C2.
      Annotation of the 173,747- and 98,760-bp BACs showed that gene conservation in
      both order and orientation is high between homeologous regions with only a single
      gene insertion/deletion and local tandem duplications differing between the
      regions. The nucleotide sequence conservation extends into intergenic regions as
      well, probably due to conserved regulatory sequences. Most of the homeologs
      appear to have a role in either transcription/DNA binding or cellular signaling,
      suggesting a potential preference for retention of duplicate genes with these
      functions. Reverse transcriptase-PCR analysis of homeologs showed that in the
      tissues sampled, most homeologs have not diverged greatly in their transcription
      profiles. However, four cases of changes in transcription were identified,
      primarily in the HCBT gene cluster. Because a mapped locus corresponds to a
      soybean cyst nematode (SCN) QTL, the potential role of HCBT genes in response to
      SCN is discussed. These results are the first sequenced-based analysis of
      homeologous BACs in soybean, a diploidized paleopolyploid.

PMID- 16888342
TI  - Genetic analysis of slipper/mixed lineage kinase reveals requirements in multiple
      Jun-N-terminal kinase-dependent morphogenetic events during Drosophila
      development.
AB  - Mixed lineage kinases (MLKs) function as Jun-N-terminal kinase (JNK) kinase
      kinases to transduce extracellular signals during development and homeostasis in
      adults. slipper (slpr), which encodes the Drosophila homolog of mammalian MLKs,
      has previously been implicated in activation of the JNK pathway during embryonic
      dorsal epidermal closure. To further define the specific functions of SLPR, we
      analyzed the phenotypic consequences of slpr loss and gain of function throughout
      development, using a semiviable maternal-effect allele and wild-type or dominant
      negative transgenes. From these analyses we confirm that failure of dorsal
      closure is the null phenotype in slpr germline clones. In addition, there is a
      functional maternal contribution, which can suffice for embryogenesis in the
      zygotic null mutant, but rarely suffices for pupal metamorphosis, revealing later
      functions for slpr as the maternal contribution is depleted. Zygotic null mutants
      that eclose as adults display an array of morphological defects, many of which
      are shared by hep mutant animals, deficient in the JNK kinase (JNKK/MKK7)
      substrate for SLPR, suggesting that the defects observed in slpr mutants
      primarily reflect loss of hep-dependent JNK activation. Consistent with this, the
      maternal slpr contribution is sensitive to the dosage of positive and negative
      JNK pathway regulators, which attenuate or potentiate SLPR-dependent signaling in
      development. Although SLPR and TAK1, another JNKKK family member, are
      differentially used in dorsal closure and TNF/Eiger-stimulated apoptosis,
      respectively, a Tak1 mutant shows dominant genetic interactions with slpr,
      suggesting potential redundant or combinatorial functions. Finally, we
      demonstrate that SLPR overexpression can induce ectopic JNK signaling and that
      the SLPR protein is enriched at the epithelial cell cortex.

PMID- 16888346
TI  - Use of genome browsers to locate your favorite genes.
AB  - The completion of whole-genome sequencing projects offers the opportunity of
      creating high-resolution maps of specific segments in a known genomic DNA
      sequence. For this purpose, several genome browsers have been created. They
      include the map-view (http://www.ncbi.nlm.nih.gov/mapview/), the Ensembl genome
      browser (http://www.ensembl.org/), and the genome browser at UCSC
      (http://genome.ucsc.edu/). For the beginners in the field, through a specific
      example, this chapter provides a step-by-step procedure for creating a map using
      the genome browser at UCSC. The example describes mapping, in the human genome,
      the promoter region of the NF-IL6 gene. The procedure is applicable to creating
      maps of the desired regions in genomes of other species available at the genome
      browser at UCSC.

PMID- 16888345
TI  - Population genetics models of competition between transposable element
      subfamilies.
AB  - Transposable elements are one of the major components of genomes. Some copies are
      fully efficient; i.e., they are able to produce the proteins needed for their own
      transposition, and they can move and duplicate into the genome. Other copies are
      mutated. They may have lost their moving ability, their coding capacity, or both,
      thus becoming pseudogenes slowly eliminated from the genome through deletions and
      natural selection. Little is known about the dynamics of such mutant elements,
      particularly concerning their interactions with autonomous copies. To get a
      better understanding of the transposable elements' evolution after their initial
      invasion, we have designed a population genetics model of transposable elements
      dynamics including mutants or nonfunctional sequences. We have particularly
      focused on the case where these sequences are nonautonomous elements, known to be
      able to use the transposition machinery produced by the autonomous ones. The
      results show that such copies generally prevent the system from achieving a
      stable transposition-selection equilibrium and that nonautonomous elements can
      invade the system at the expense of autonomous ones. The resulting dynamics are
      mainly cyclic, which highlights the similarities existing between genomic selfish
      DNA sequences and host-parasite systems.

PMID- 16888344
TI  - Genetic variation in Drosophila melanogaster resistance to infection: a
      comparison across bacteria.
AB  - Insects use a generalized immune response to combat bacterial infection. We have
      previously noted that natural populations of D. melanogaster harbor substantial
      genetic variation for antibacterial immunocompetence and that much of this
      variation can be mapped to genes that are known to play direct roles in immunity.
      It was not known, however, whether the phenotypic effects of variation in these
      genes are general across the range of potentially infectious bacteria. To address
      this question, we have reinfected the same set of D. melanogaster lines with
      Serratia marcescens, the bacterium used in the previous study, and with three
      additional bacteria that were isolated from the hemolymph of wild-caught D.
      melanogaster. Two of the new bacteria, Enterococcus faecalis and Lactococcus
      lactis, are gram positive. The third, Providencia burhodogranaria, is gram
      negative like S. marcescens. Drosophila genotypes vary highly significantly in
      bacterial load sustained after infection with each of the four bacteria, but mean
      loads are largely uncorrelated across bacteria. We have tested statistical
      associations between immunity phenotypes and nucleotide polymorphism in 21
      candidate immunity genes. We find that molecular variation in some genes, such as
      Tehao, contributes to phenotypic variation in the suppression of only a subset of
      the pathogens. Variation in SR-CII and 18-wheeler, however, has effects that are
      more general. Although markers in SR-CII and 18-wheeler explain >20% of the
      phenotypic variation in resistance to L. lactis and E. faecalis, respectively,
      most of the molecular polymorphisms tested explain <10% of the total variance in
      bacterial load sustained after infection.

PMID- 16888347
TI  - Methods for identifying and mapping recent segmental and gene duplications in
      eukaryotic genomes.
AB  - The aim of this chapter is to provide instruction for analyzing and mapping
      recent segmental and gene duplications in eukaryotic genomes. We describe a
      bioinformatics-based approach utilizing computational tools to manage eukaryotic
      genome sequences to characterize and understand the evolutionary fates and
      trajectories of duplicated genes. An introduction to bioinformatics tools and
      programs such as BLAST, Perl, BioPerl, and the GFF specification provides the
      necessary background to complete this analysis for any eukaryotic genome of
      interest.

PMID- 16888348
TI  - Identification and mapping of paralogous genes on a known genomic DNA sequence.
AB  - The completion of whole genome sequencing projects offers the opportunity to
      examine the organization of genes and the discovery of evolutionarily related
      genes in a given species. For the beginners in the field, through a specific
      example, this chapter provides a step-by-step procedure for identifying
      paralogous genes, using the genome browser at UCSC (http://genome.ucsc.edu/). The
      example describes identification and mapping in the human genome, the paralogs of
      TCF12/HTF4. The example identifies TCF3 and TCF4 as paralogs of the TCF12/HTF4
      gene. The example also identifies a related sequence, corresponding to a
      pseudogene, in one of the introns of the JAK2 gene. The procedure described
      should be applicable to the discovery and creation of maps of paralogous genes in
      the genomic DNA sequences that are available at the genome browser at UCSC.

PMID- 16888349
TI  - Quantitative DNA fiber mapping in genome research and construction of physical
      maps.
AB  - Efforts to prepare a first draft of the human DNA genomic sequence forced
      multidisciplinary teams of researchers to face unique challenges. At the same
      time, these unprecedented obstacles stimulated the development of many highly
      innovative approaches to biomedical problem solving, robotics, and
      bioinformatics. High-resolution physical maps are required for ordering
      individual segments of information for the construction of a comprehensive map of
      the entire genome. This chapter describes a novel way to identify, delineate, and
      characterize selected, often small DNA sequences along a larger piece of the
      human genome. The technology is based on immobilization of high molecular weight
      DNA molecules on a solid substrate (such as a glass slide) followed by uniform
      stretching of the DNA molecule by the force of a receding meniscus. The
      hydrodynamic force stretches the DNA molecules homogeneously to approximately 2.3
      kb/microm, so that distances measured after probe binding in microm can be
      converted directly into kb distances. Out of a large number of applications, this
      article focuses on mapping of genomic sequences relative to one another, the
      assembly of physical maps with near kb resolution, and, finally, quality control
      during physical map assembly and sequencing.

PMID- 16888350
TI  - PRINS for mapping single-copy genes.
AB  - Primed in situ labeling (PRINS) is a sensitive and specific method that can be
      used for the localization of single copy genes and sequences too small for
      detection by conventional fluorescence in situ hybridization. By the use of
      PRINS, the human SRY gene was localized to Yp11.31-p11.32 and the SOX3 gene to
      Xq26-q27. In other studies, we localized specific deletions of RBM and DAZ,
      candidate genes for AZF (azoospermia factor) to proximal Yq11.2, the AZF region,
      in an infertile male. Locus-specific oligonucleotide probes (PRINS primers) were
      annealed to chromosomal DNA in situ and extended on preparations fixed on glass
      slides in the presence of dATP, dCTP, dGTP, dTTP, biotin-16-dUTP, and Taq DNA
      polymerase. After addition of avidin-conjugated fluorophore, signals were
      visualized by fluorescence microscopy in metaphase spreads from patients and
      controls. With further development, the PRINS method may prove useful for
      localization of single-copy genes, in general, and for the detection of gene
      deletions.

PMID- 16888351
TI  - VISTA family of computational tools for comparative analysis of DNA sequences and
      whole genomes.
AB  - Comparative analysis of DNA sequences is becoming one of the major methods for
      discovery of functionally important genomic intervals. Presented here the VISTA
      family of computational tools was built to help researchers in this undertaking.
      These tools allow the researcher to align DNA sequences, quickly visualize
      conservation levels between them, identify highly conserved regions, and analyze
      sequences of interest through one of the following approaches: . Browse
      precomputed whole-genome alignments of vertebrates and other groups of organisms.
      . Submit sequences to Genome VISTA to align them to whole genomes. . Submit two
      or more sequences to mVISTA to align them with each other (a variety of alignment
      programs with several distinct capabilities are made available).. Submit
      sequences to Regulatory VISTA (rVISTA) to perform transcription factor binding
      site predictions based on conservation within sequence alignments.Use stand-alone
      alignment and visualization programs to run comparative sequence analysis locally
      All VISTA tools use standard algorithms for visualization and conservation
      analysis to make comparison of results from different programs more
      straightforward. The web page http://genome.lbl.gov/vista/ serves as a portal for
      access to all VISTA tools. Our support group can be reached by email at
      vista@lbl.gov.

PMID- 16888352
TI  - Computational prediction of cis-regulatory modules from multispecies alignments
      using Galaxy, Table Browser, and GALA.
AB  - One major goal of genomics is to identify all the functional sequences in
      genomes, including sequences that regulate the expression of genes. Sequence
      conservation is a good, albeit imperfect, guide to these functional elements. We
      describe how to use publicly available servers (Galaxy, the UCSC Table Browser,
      and GALA) to find genomic sequences whose alignments (from blastZ and multiZ)
      show properties associated with cis-regulatory modules, such as high conservation
      score, high regulatory potential score, and conserved transcription factor
      binding sites. Links to these servers can be accessed at http://www.bx.psu.edu/
      and http://genome.ucsc.edu/.

PMID- 16888354
TI  - cis-regulatory region analysis using BEARR.
AB  - Genome-wide studies are fast becoming the norm, partly fueled by the availability
      of genome sequences and the feasibility of high-throughput experimental
      platforms, e.g., microarrays. An important aspect in any genome-wide studies is
      determination of regulatory relationships, believed to be primarily transacted
      through transcription factor binding to DNA. Identification of specific
      transcription factor binding sites in the cis-regulatory regions of genes makes
      it possible to list direct targets of transcription factors, model
      transcriptional regulatory networks, and mine other associated datasets for
      relevant targets for experimental and clinical manipulation. We have developed a
      web-based tool to assist biologists in efficiently carrying out the analysis of
      genes from studies of specific transcription factors or otherwise. The batch
      extraction and analysis of cis-regulatory regions (BEARR) facilitates
      identification, extraction, and analysis of regulatory regions from the large
      amount of data that is typically generated in genome-wide studies. This chapter
      highlights features and serves as a tutorial for using this publicly available
      software. The URL is http://giscompute.gis.a-star.edu.sg/~vega/BEARR1.0/.

PMID- 16888353
TI  - Comparative promoter analysis in vertebrate genomes with the CORG workbench.
AB  - CORG is a versatile web-based workbench for comparative promoter analysis in
      vertebrate model organisms. Two kinds of information are explicitly considered in
      the automated annotation process. First, local conservation patterns in upstream
      regions of homologous genes: These phylogenetic footprints are likely to stem
      from sequence elements that are under selective pressure. The CORG pipeline
      detects and exploits patterns of local similarity to annotate promoter regions.
      Second, experimental data on transcription start sites: exon positions and DNA
      binding site descriptions complete the promoter annotation. These data are made
      available via an interactive web portal. Individual promoter studies are
      supported by a JAVA applet that supplies all data down to the nucleotide level.

PMID- 16888355
TI  - A database of 9-mers from promoter regions of human protein-coding genes.
AB  - Discovery of lexical characteristics of specific sequence motifs in human genomic
      DNA can help with predicting and classifying regulatory cis elements according to
      the genes they control. In lexical models, some "words" may serve as downstream
      targets of signaling systems, whereas other "words" may specify sequences that
      selectively control the expression of a subset of genes to produce the various
      cell types and tissues. To discover lexical features of potential regulatory
      "words," we have created a database of 9-mers derived from the promoter regions
      of a subset of human protein-coding genes. This report describes the procedure
      for extracting information from that database through the web.

PMID- 16888356
TI  - A program toolkit for the analysis of regulatory regions of genes.
AB  - A major challenge in systems biology is to discover and reconstruct the cis
      regulatory networks through which the expression of genes is controlled. Even
      though a variety of sequences have been shown to interact with the transcription
      factors that bind DNA, extensive work is needed to discover and classify
      regulatory "codes" and to elucidate the role played by the sequence context of
      genomic DNA in the regulation of genes. Databases of sequence elements extracted
      from regulatory regions may facilitate this process. This report provides a
      Toolkit and instructions for creating a database for collecting and analyzing 9
      base elements (9-mers) from a large collection of DNA sequences. A reference set
      consisting of all possible 9-mers is included for extracting potential control
      elements, irrespective of their orientation and order in DNA.

PMID- 16888357
TI  - Analysis of allele-specific gene expression.
AB  - The analysis of allele-specific gene expression has been of long-standing
      interest in the study of genomic imprinting, but there is growing awareness that
      differences in allelic expression are widespread among autosomal nonimprinted
      genes. Recent research into cis-acting regulatory polymorphisms has utilized the
      analysis of allele-specific gene expression to identify functionally important
      regulatory haplotypes and specific genetic polymorphisms. Allele-specific effects
      are typically of modest magnitude, requiring techniques for analysis of high
      sensitivity and specificity. Here, strategic approaches to the analysis of allele
      specific gene expression are reviewed with protocols for in vivo analysis. These
      include analysis of the relative allelic abundance of transcribed RNA and of
      transcription factor recruitment and Pol II loading by chromatin
      immunoprecipitation.

PMID- 16888358
TI  - Construction of microRNA-containing vectors for expression in mammalian cells.
AB  - MicroRNAs (miRNAs) are a class of noncoding RNAs that regulate gene expression by
      single-stranded RNAs of 18 to 25 nucleotides in length. Hundreds of miRNAs have
      been found in animals and plants, some of which play important roles in
      development or differentiation. Increasing attention has thus been paid to their
      biogenesis and regulation mechanisms and the identification of target genes. We
      are constructing a comprehensive expression vector library containing predicted
      human miRNAs. miRNA expression vectors containing human RNA polymerase II or III
      promoters, and utilizing a flexible vector system, can be useful for functional
      analysis.

PMID- 16888359
TI  - Mining microarray data at NCBI's Gene Expression Omnibus (GEO)*.
AB  - The Gene Expression Omnibus (GEO) at the National Center for Biotechnology
      Information (NCBI) has emerged as the leading fully public repository for gene
      expression data. This chapter describes how to use Web-based interfaces,
      applications, and graphics to effectively explore, visualize, and interpret the
      hundreds of microarray studies and millions of gene expression patterns stored in
      GEO. Data can be examined from both experiment-centric and gene-centric
      perspectives using user-friendly tools that do not require specialized expertise
      in microarray analysis or time-consuming download of massive data sets. The GEO
      database is publicly accessible through the World Wide Web at
      http://www.ncbi.nlm.nih.gov/geo.

PMID- 16888360
TI  - The Stanford Microarray Database: a user's guide.
AB  - The Stanford Microarray Database (SMD) is a DNA microarray research database that
      provides a large amount of data for public use. This chapter describes the use of
      the primary tools for searching, browsing, retrieving, and analyzing data
      available for SMD. With this introduction, researchers and students will be able
      to examine and analyze a large body of gene expression and other experiments.
      Additional tools for depositing, annotating, sharing, and analyzing data,
      available only to registered users, are also described. SMD is available for
      installation as a local database.

PMID- 16888361
TI  - Detecting nucleosome ladders on unique DNA sequences in mouse liver nuclei.
AB  - Nucleosome arrangements and possibly chromatin higher order structures differ in
      different regions of genomic DNA, and these differences could be functionally
      important. Nucleosome arrangements are reflected by the nucleosome ladders they
      give rise to upon micrococcal nuclease digestion of the chromatin. Here we
      describe how Southern hybridization can be used to detect the nucleosome ladders
      arising from different regions of DNA in mouse liver nuclei.

PMID- 16888362
TI  - DNA methyltransferase probing of DNA-protein interactions.
AB  - Effective methods of probing chromatin structure without disrupting DNA-protein
      interactions and associations are necessary for creating an accurate picture of
      chromatin and its processes in vivo. Expression of cytidine-5 DNA
      methyltransferases (C5 DMTases) in Saccharomyces cerevisiae provides a powerful
      noninvasive method of assaying relative DNA accessibility in chromatin. DNA
      MTases are occluded from protein-associated DNA based on the strength and span of
      the DNA-protein interaction. Ectopic regulation of C5 DMTase expression systems
      allows for minimal disruption of yeast physiology. Methylated sites are detected
      by bisulfite genomic sequencing, which leads to a positive signal corresponding
      to modified cytidine residues. High-resolution C5 DMTases with dinucleotide
      recognition specificity are shown to provide sufficient coverage to map
      interactions spanning a relatively short distance.

PMID- 16888363
TI  - Protein binding microarrays (PBMs) for rapid, high-throughput characterization of
      the sequence specificities of DNA binding proteins.
AB  - DNA binding proteins play a number of key roles in cells, in processes including
      transcriptional regulation, recombination, genome rearrangements, and DNA
      replication, repair, and modification. Of particular interest are the
      interactions between transcription factors and their DNA binding sites, as they
      are an integral part of the transcriptional regulatory networks that control gene
      expression. Despite their importance, the DNA binding specificities of most DNA
      binding proteins remain unknown, as earlier technologies aimed at characterizing
      DNA-protein interactions have been time consuming and not highly scalable. We
      have developed a new DNA microarray-based technology, termed protein binding
      microarrays (PBMs), that allows rapid, high-throughput characterization of the in
      vitro DNA binding site sequence specificities of transcription factors in a
      single day. The resulting DNA binding site data can be used in a number of ways,
      including for the prediction of the genes regulated by a given transcription
      factor, annotation of transcription factor function, and functional annotation of
      the predicted target genes.

PMID- 16888364
TI  - Quantitative profiling of protein-DNA binding on microarrays.
AB  - Recent studies on genome-wide localization of transcription factor (TF) binding
      to DNA have shown that a large proportion of identified sequences do not contain
      consensus motifs predicted by databases of transcription factor binding sites,
      such as TRANSFAC. The main limitation of these databases is that they are based
      on a literature search of published examples of binding; consequently the data
      are not from a systematic survey and may be subject to sampling biases if
      investigators focused on particular motifs. Thus, there is an urgent need for
      systematic profiling of vertebrate transcription factor binding to DNA. We have
      developed a high-throughput platform for the quantitative analysis of protein-DNA
      interactions based on microarray technology.

PMID- 16888366
TI  - Isolation and mass spectrometry of specific DNA binding proteins.
AB  - A subset of the proteome that binds to specific DNA sequences is at the center of
      genome function, integrity, and dynamics. We present a detailed protocol that
      allows the isolation of any specific DNA binding protein and its subsequent
      identification by mass spectrometry. The procedure involves prefractionation of
      crude nuclear extract by phosphocellulose (P11) chromatography, followed by a
      series of positive/negative selections on wild-type and site-mutated ligand DNA
      in a magnetic microparticulate format. DNA-affinity capture requires
      concatamerized and biotinylated ligand, selective salt conditions, and improved
      competitor DNAs. The amount of protein(s) captured on DNA-magnetic beads is
      generally sufficient for successful MALDI-TOF and TOF/TOF MS-based protein
      identification. As an example, we describe the procedures used to isolate and
      identify four specific transcription factors from 2 x 10(9) promyelocytic NB4
      cells.

PMID- 16888365
TI  - Analysis of protein-DNA binding by streptavidin-agarose pulldown.
AB  - Binding of nuclear transactivators to sequence-specific regulatory elements on
      the promoter regions is of fundamental importance in gene expression and
      regulation. DNA-bound transactivators recruit transcription coactivators or
      repressors and an array of associated proteins that interact with the basal
      transcription factors, thereby activating the transcription machinery. Analysis
      of the large complex of proteins that bind to DNA is an important step in
      elucidating the mechanisms by which gene expressions are regulated. Commonly used
      techniques to determine DNA-protein binding such as the electrophoretic mobility
      shift assay (EMSA) have limited value for analyzing simultaneously a large number
      of proteins in the complex. We describe here a streptavidin-agarose pulldown
      assay that is capable of analyzing quantitatively binding of an array of proteins
      to DNA probes. The assay is easy to perform and does not require radiolabeled
      probes. It involves incubation of nuclear extract proteins with 5'biotinylated
      double-stranded DNA probes and streptavidin-agarose beads. The complex is pulled
      down, and proteins in the complex are dissociated and analyzed by Western
      blotting. This method has been shown to be useful in determining the regulation
      of binding of transactivators, p300/CBP, and associated proteins to the
      cyclooxygenase-2 (COX-2) promoter.

PMID- 16888367
TI  - Isolation of transcription factor complexes by in vivo biotinylation tagging and
      direct binding to streptavidin beads.
AB  - Efficient tagging methodologies are an integral aspect of protein complex
      characterization by proteomic approaches. Owing to the very high affinity of
      biotin for avidin and streptavidin, biotinylation tagging offers an attractive
      approach for the efficient purification of protein complexes. The very high
      affinity of the biotin/(strept)avidin system also offers the potential for the
      single-step capture of lower abundance protein complexes, such as transcription
      factor complexes. The identification of short peptide tags that are efficiently
      biotinylated by the bacterial BirA biotin ligase led to an approach for the
      single-step purification of transcription factor complexes by specific in vivo
      biotinylation tagging. A short sequence tag fused N-terminally to the
      transcription factor of interest is very efficiently biotinylated by BirA
      coexpressed in the same cells, as was demonstrated by the tagging of the
      essential hematopoietic transcription factor GATA-1. The direct binding to
      streptavidin of biotinylated GATA-1 in nuclear extracts resulted in the single
      step capture of the tagged factor and associated proteins, which were eluted and
      identified by mass spectrometry. This led to the characterization of several
      distinct GATA-1 complexes with other transcription factors and chromatin
      remodeling cofactors, which are involved in activation and repression of gene
      targets. Thus, BirA-mediated tagging is an efficient approach for the direct
      capture and characterization of transcription factor complexes.

PMID- 16888368
TI  - The clinician through the looking glass: sputum microbiology in COPD
      exacerbations.

PMID- 16888369
TI  - What's a good night's sleep worth?

PMID- 16888370
TI  - Effects of calcitriol on type 5b tartrate-resistant acid phosphatase and
      interleukin-6 in secondary hyperparathyroidism.
AB  - BACKGROUND/AIMS: Secondary hyperparathyroidism (SHP) is characterized by high
      bone turnover and elevated serum bone remodeling markers. Elevation of serum
      interleukin-6 (IL-6) levels is also characteristic of end-stage renal disease.
      This study investigates the effects of intravenous calcitriol on serum bone
      resorptive markers, namely, type 5b tartrate-resistant acid phosphatase (TRACP5b)
      and IL-6 in patients with SHP. METHODS: Intravenous calcitriol therapy was given
      for 16 weeks to 24 patients on maintenance hemodialysis with plasma intact
      parathyroid hormone (iPTH) levels >300 pg/ml. Blood was drawn at baseline and
      every 4 weeks for 16 weeks for determination of the levels of biochemical
      parameters, iPTH, IL-6 and bone remodeling markers, including bone-specific
      alkaline phosphatase (bAP) and TRACP5b. RESULTS: Only 21 patients responded to
      the calcitriol therapy, with significant decrements in serum iPTH after 4 weeks
      of therapy and thereafter. After 16 weeks of calcitriol therapy, 21 patients had
      significant decrements in serum iPTH (707.9 +/- 317.8 vs. 205.0 +/- 63.1 pg/ml, p
      < 0.01). Prior to treatment, a significant correlation was found between
      increased levels of serum iPTH and IL-6 levels (r = 0.45, p < 0.05). After
      treatment, there was also a significant and parallel lowering of levels of serum
      iPTH, IL-6 (8.52 +/- 3.59 vs. 7.24 +/- 2.81 pg/ml, p < 0.01), bAP (54.68 +/-
      36.17 vs. 24.55 +/- 13.84 U/l, p < 0.01) and TRACP5b (3.41 +/- 1.89 vs. 1.80 +/-
      0.55 U/l, p < 0.01). Our results additionally showed significant positive
      correlationsbetween baseline levels of serum IL-6 and those of iPTH, bAP and
      TRACP5b. After 16 weeks of calcitriol treatment, the correlation between IL-6 and
      iPTH levels lost significance but levels of serum IL-6, bAP and TRACP5b remained
      significantly correlated. CONCLUSIONS: Elevated levels of serum IL-6 and bone
      remodeling markers, namely, bAP and TRACP5b which are common features of SHP, are
      effectively suppressed by calcitriol therapy. This indicates that
      hyperparathyroidism not only accelerates bone remodeling but may also aggravate
      inflammation in patients on maintenance hemodialysis.

PMID- 16888371
TI  - Incidence and prevention of ischemic stroke following myocardial infarction:
      review of current literature.
AB  - Myocardial infarction is the leading cause of death today. With the fast progress
      in pharmacotherapy and revascularization technology, outcomes following a
      myocardial infarction have become very favorable. While most of the complications
      from a myocardial infarction can be adequately managed, thus leading to reduced
      mortality, stroke following a myocardial infarction remains a challenge even
      today, and can lead to potentially devastating complications. We discuss the
      incidence, pathophysiology, and management options of non-hemorrhagic stroke
      following a myocardial infarction.

PMID- 16888372
TI  - Johann Jacob Wepfer Award 2006 of the ESC to Prof. Markku Kaste.

PMID- 16888373
TI  - Evidence, education and practice.
AB  - Stroke causes greater loss of quality-adjusted life years than any other disease
      and is also one of the most expensive disorders. The burden of stroke will
      increase in the future due to change in the age structure of populations. We have
      a vast body of evidence on how to prevent stroke and how to treat stroke
      patients. Good examples are treatment of hypertension, antithrombotic agents and
      carotid surgery in stroke prevention, thrombolysis in ischaemic stroke and stroke
      unit care for all stroke patients. We only have to translate scientific evidence
      into daily practice. If some pieces are missing, it is our duty to generate them
      through research. While taking part in randomized clinical trials (RCTs), the
      discipline, an essential part of RCTs, will improve the daily care of all stroke
      patients. Besides RCTs there are many other sources of scientific evidence for
      stroke management, one of which is the European Stroke Initiative (EUSI). The
      mission of the EUSI is to improve and optimize stroke management in Europe
      through education and by offering best practice guidelines. Also national and
      international societies and organizations play an important role in providing
      education. The human factor is one obstacle to more successful stroke management
      because to be more effective we must change our own clinical routine. We can make
      a difference by applying available evidence to our daily practice.

PMID- 16888374
TI  - Barthel index in a Middle-East country: translation, validity and reliability.
AB  - BACKGROUND: In Iran, a Middle-East country, no disability scale has been
      translated and validated for use in stroke clinical trials. This study was
      designed to translate the Barthel Index and make its Persian translated form
      valid and reliable. METHODS: All items of the Barthel Index were translated into
      Persian. Also, the Modified Rankin Scale (MRS) was also translated to Persian.
      Telephone interview was used as the method of data acquisition. Two interviewers
      were chosen for this means in order to accelerate data gathering and measure
      interrater agreement. Samples were selected from Isfahan Cardiovascular Research
      Center's Stroke Registry Unit, a WHO collaborating center in the center of Iran.
      All the patients were registered as stroke or intracerebral hemorrhage (ICH).
      These patients were inhabitants of Isfahan Province who had suffered from stroke
      or ICH between 12 and 24 months before data acquisition. Chronbach's alpha, test
      retest reliability, concurrent validity with MRS, interrater agreement and item
      analysis were done for the translated questionnaire. RESULTS: Translated
      questionnaires were filled by interview from 459 stroke patients. Their mean age
      was 68.11 +/- 11.59 years. 243 of them were male (52.9%). Cronbach's alpha was
      0.9354. Spearman's correlation coefficient between translated Barthel Index
      scores and MRS scores was -0.912. Spearman's correlation coefficient between 2
      scores, to determine test-retest reliability was 0.989. Concordance correlation
      to determine interrater agreement was 0.994. All corrected item-total
      correlations were greater than 0.5. CONCLUSIONS: The Persian translated version
      of the Barthel Index is a reliable and valid questionnaire for use in stroke
      clinical trials.

PMID- 16888375
TI  - High blood pressure in acute ischemic stroke and underlying disorders.
AB  - BACKGROUND: The Acute Candesartan Cilexetil Therapy in Stroke Survivors (ACCESS)
      study indicated that early treatment with an angiotensin type 1 receptor blocker
      in acute stroke patients who had relatively high blood pressure improved
      cardiovascular morbidity and mortality in the chronic stage. To better interpret
      the findings of this study, we determined whether stroke patients with high acute
      blood pressure had specific underlying conditions. METHODS: We divided 712
      consecutive patients who were hospitalized within 48 h after the onset of brain
      infarction into two groups: 77 patients with high acute blood pressure that met
      the criteria of the ACCESS study and the 635 remaining patients. Underlying risk
      factors and comorbidities, stroke characteristics, as well as mortality, vascular
      events, and disability at 3 weeks were compared between the two groups. RESULTS:
      Patients with high acute blood pressure more frequently had diabetes mellitus (p
      < 0.01), intracranial arterial stenosis (p < 0.02), higher levels of hemoglobin
      A1c (p < 0.005), higher creatinine levels (p < 0.005), and tended to more
      frequently have ischemic heart disease (p < 0.09) and infarcts <1.5 cm in
      diameter (p < 0.09) than the other patients. On multivariate analysis, high
      levels of hemoglobin A1c, high creatinine levels, and intracranial arterial
      stenosis were independently predictive of high acute blood pressure. At 3 weeks
      after the stroke onset, patients with high acute blood pressure were more
      dependent in their daily living activities (p < 0.02) and more frequently
      developed vascular events or death (p < 0.005) than the other patients.
      CONCLUSIONS: Poorly controlled diabetes mellitus and advanced renal damage
      appeared to correlate with acute hypertension after stroke. Since intracranial
      arterial stenosis also seemed to contribute to high acute blood pressure, one
      should be careful not to induce cerebral hypoperfusion by the early use of
      antihypertensives.

PMID- 16888376
TI  - CT angiography in acute stroke: does it provide additional information on
      occurrence of infarction and functional outcome after 3 months?
AB  - OBJECTIVE: To investigate whether acute phase intracranial CT angiography (CTA)
      independently predicts infarction and functional outcome in ischemic stroke.
      METHODS: Hundred and fifty-one consecutive patients with acute (<12 h) ischemic
      stroke who received intracranial CTA were investigated. Stroke severity on
      admission was determined using the National Institute of Health Stroke Scale
      (NIHSS). Reconstructed CTAs were investigated for relevant pathology. Follow-up
      imaging was performed 24-48 h after admission. Functional outcome was assessed
      after 3 months using the modified Rankin scale. Single factor and multiple
      logistic regression analyses were performed to predict infarction and dependency
      (modified Rankin scale > or = 3) on follow-up. RESULTS: Median NIHSS on admission
      was 10 (IQR 3-14). Out of the 151 patients, 61 (40%) had pathological CTA
      findings. Infarction was demonstrated in 60/61 patients (98%) with and in 67/90
      patients (74%) without vessel pathology. Presence of infarction on follow-up
      imaging and dependency at 3 months were correlated with pathological CTA findings
      on admission in single factor analysis (each p < 0.001). After adjustment for age
      (> or =/<65 years), NIHSS (> or =/<10), sex, therapy, and time to presentation (>
      or =/<3 h), only NIHSS > or = 10 on admission was predictive of dependency at
      follow-up (p < 0.001). CONCLUSIONS: Pathological CTA findings in the acute phase
      of ischemic stroke do not independently predict a poor outcome at 3 months after
      acute stroke.

PMID- 16888377
TI  - High prevalence of abnormal glucose metabolism and poor sensitivity of fasting
      plasma glucose in the chronic phase of stroke.
AB  - BACKGROUND: Cardiovascular disease is the leading cause of death in long-term
      stroke survivors, and whole-body glucose metabolism is strongly linked to
      cardiovascular disease risk. This study provides important preliminary
      information on the prevalence of abnormal glucose metabolism in chronic stroke
      patients (mean 3 years after stroke) and reports on the utility of screening for
      abnormalities using fasting plasma glucose (FPG) in this population. METHODS: Two
      hundred and sixteen chronic hemiparetic stroke patients were screened for
      diabetes status by medical history and FPG. A subset (n = 80) was evaluated by
      oral glucose tolerance test to assess the utility of screening for abnormalities
      using FPG alone. RESULTS: Seventy-five of the 216 (35%) had type 2 diabetes by
      medical history. Another 70 were either diabetic (n = 11) or had impaired fasting
      glucose (n = 59) based on a single blood draw at the time of screening. FPG among
      non-diabetic stroke patients had a sensitivity of 49% for predicting
      abnormalities in the 2-hour glucose level during oral glucose tolerance test.
      Cumulative results identify 77% as abnormal (impaired or diabetic) on the basis
      of medical history, fasting plasma glucose, and/or 2-hour glucose level.
      CONCLUSIONS: The prevalence of abnormal glucose metabolism is extremely high in
      chronic stroke and is underestimated on the basis of FPG.

PMID- 16888378
TI  - Could platelet aggregation ratio be an indicator for differential diagnosis of
      transient ischemic attack and cerebral ischemic stroke?
AB  - BACKGROUND: Platelet aggregation plays an important role in the pathogenesis of
      thromboembolic cerebrovascular disease. Platelet aggregation ratio (PAR) and its
      derivates have been used successfully to identify the effectiveness of
      antiplatelet agents and their optimum dosage in patients suffering from stroke.
      However, we failed to find any study using PAR as a predictive factor in
      differential diagnosis of ischemic cerebrovascular diseases. In this study, we
      aimed to investigate PAR in patients with acute ischemic stroke and transient
      ischemic attack (TIA), comparing their neuroradiological features, and whether
      PAR values could be an indicator for differential diagnosis of TIA and cerebral
      ischemic stroke. METHODS: The study consisted of 75 adult patients who were
      admitted with suspected stroke and 25 control healthy individuals. All patients
      were diagnosed with acute ischemic stroke or TIA and the diagnoses were confirmed
      by clinical examination and computed tomography (CT). The stroke group consisted
      of 45, and the TIA group of 30 consecutive patients. The patients included in
      this study had noncardioembolic stroke. PAR values were measured on admission in
      all groups, according to the modified method of Wu and Hoak. The statistical
      significance of differences was evaluated using one-way ANOVA, the unpaired
      Student t test and the Bonferroni and Tamhane post hoc tests. RESULTS:
      Differences in PARs between the control and TIA groups, control and stroke groups
      and stroke and TIA groups were significant (p < 0.001). Nevertheless, in each
      group, differences between genders were not statistically significant. Initial CT
      scan demonstrated early infarction sign in 26 stroke patients (57%); however, in
      19 stroke patients, it was not detected. Differences in PARs between TIA and
      stroke patients, whose initial CT scan findings were negative, were found to be
      significant. However, differences in PARs between CT negative stroke patients and
      positive stroke patients were not significant. CONCLUSION: We believe that the
      use of PAR values in the assessment of acute ischemic stroke and TIA could open
      up a new perspective in the management of such patients. In differential
      diagnosis, PAR values have to combine with neurological examination and CT scan
      signs. The current test is not able to differentiate vascular occlusive diseases
      in other organs from vascular occlusive problems in the brain. Further study is
      needed to determine the sensitivity and specificity of this test in all patients
      and to confirm the prognostic value in stroke patients.

PMID- 16888379
TI  - Predictors of cerebral microbleeds in acute ischemic stroke and TIA patients.
AB  - BACKGROUND: Cerebral microbleeds (CMB) detected on gradient-echo T2*-weighted MRI
      have been associated with cognitive impairment and the potential for increased
      risk of intracranial hemorrhage. We evaluated risk factors for these
      microangiopathic lesions in a cohort of stroke and transient ischemic attack
      patients. METHODS: Presence and number of CMB in consecutive acute stroke
      patients admitted to a university hospital stroke service over an 18-month period
      were rated. Multivariate models were generated to determine the contribution of
      21 demographic and clinical variables to the frequency and number of CMB.
      RESULTS: Of 164 patients (mean age 71 years, 52% female), 57 (35%) had CMB
      evident on gradient-echo T2*-weighted MRI. CMB were more commonly noted among
      patients with small vessel disease ischemic stroke mechanism (47%) than large
      vessel atherothromboembolic (12%) or cardioembolic (18%, p = 0.0001). In
      univariate analysis, patients with CMB were older, (p = 0.008), more likely to
      have been on >1 antihypertensive prior to admission (p = 0.024) than those
      without CMB. In multivariate logistic regression analyses, presumed small vessel
      stroke subtype, history of atrial fibrillation, being on >1 antihypertensive
      prior to admission, and smoking were independent factors increasing the risk of
      CMB. Logistic regression analysis by number of CMB showed almost similar
      findings. CONCLUSIONS: CMB are more frequently noted in hospitalized stroke and
      transient ischemic attack patients with small vessel ischemia, as well as those
      with important modifiable vascular risk factors like atrial fibrillation and
      smoking.

PMID- 16888380
TI  - Does clinical-CT 'mismatch' predict early response to treatment with recombinant
      tissue plasminogen activator?
AB  - BACKGROUND: We hypothesized that patients with clinically severe strokes but less
      severe early ischemic changes on brain CT (i.e., clinical-CT mismatch) may
      respond better to intravenous recombinant tissue plasminogen activator (i.v. rt
      PA) within 3 h of symptom onset. METHODS: In this secondary analysis of the
      CLOTBUST data, patients with middle cerebral artery occlusions on transcranial
      Doppler (TCD) were treated with i.v. rt-PA. Alberta Stroke Program Early CT
      Scores were obtained with raters blinded to the NIH Stroke Scale and TCD results.
      Two mismatch criteria and three criteria of response to therapy were explored.
      RESULTS: Of 126 patients, 67% had a mismatch type 1 and 74% had a mismatch type
      2. The presence of clinical-CT mismatch by either definition did not correlate
      with any of the three criteria of response to rt-PA. Recanalization was a strong
      determinant of response, whether or not mismatch was present. CONCLUSIONS:
      Mismatch between severity of neurological deficit and CT findings is common but
      does not predict response to rt-PA therapy given within 3 h.

PMID- 16888381
TI  - NIH Stroke Scale reliability in ratings from a large sample of clinicians.
AB  - OBJECTIVE: The NIH Stroke Scale (NIHSS) is widely used in stroke clinical care
      and trials. Certification in its use, most commonly through rating of video
      vignettes, is routinely required. To investigate the reliability of the NIHSS in
      a representative sample of raters, we examined the results of the most frequently
      used certification examination. METHODS: At the invitation of the National Stroke
      Association, we analyzed the results of all raters who completed one of two
      multiple patient videotaped certification examinations from 1998 to 2004. Total
      scores for each vignette were calculated and ratings were compared based on
      percentile of responses and modified kappa scores. RESULTS: There were 7,405
      unique raters with 38,148 individual NIHSS item responses; median scores for each
      vignette ranged from 0 to 31. Total NIHSS scores varied widely between raters;
      scoring for 7 of the 11 patients (64%) had a four or more point difference in
      NIHSS score from the 5th to 95th percentile. The aphasia (kappa = 0.60) and
      facial palsy (0.65) items on the test contributed most to the variance in the
      total NIHSS score. Nurses agreed with the most common response on scoring more
      frequently than physicians (p < 0.0001). Taking the certification examination
      multiple times did not improve agreement. CONCLUSIONS: In a large diverse sample
      of clinicians, inter-rater reliability for individual elements of the NIHSS on
      videotaped vignettes was generally good, but overall scoring was inconsistent and
      could impact clinical trial results. Whether additional training, modification of
      examination elements, or clearer definitions for scoring could improve
      reliability requires further study.

PMID- 16888382
TI  - Patterns of cerebral perfusion in patients with asymptomatic internal carotid
      artery disease.
AB  - BACKGROUND: The perfusion profile of patients with asymptomatic internal carotid
      artery (ICA) disease has not been well studied. The purpose of this study is to
      describe the perfusion patterns of patients with asymptomatic ICA disease using
      computed tomography perfusion (CTP) and its potential value in identifying
      patients at higher risk for transient ischemic attacks (TIAs) or strokes.
      METHODS: We analyzed 32 patients with asymptomatic high grade ICA disease who had
      CTP and computed tomography angiography (CTA) of the head and neck. Twenty-four
      patients had severe ICA stenosis and eight had ICA occlusion. The degree of
      ipsilateral external carotid artery (ECA) and contralateral ICA stenosis, patency
      of the anterior communicating artery (ACOM), A1 segment and posterior
      communicating artery (PCOM) were evaluated in all patients. RESULTS: Sixteen
      patients had normal CTP and the other 16 patients had cerebral hypoperfusion,
      characterized by abnormalities in one or more of the three perfusion maps.
      Ipsilateral hypoplastic A1 segment was more frequent in the group with cerebral
      hypoperfusion (p = 0.025). Ipsilateral TIAs occurred in two patients, both with
      cerebral hypoperfusion. CONCLUSION: Cerebral hypoperfusion is present in half of
      the patients with asymptomatic ICA disease, predominantly in patients with a
      hypoplastic ipsilateral A1 segment. These patients likely represent a higher-risk
      group for symptomatic brain ischemia.

PMID- 16888384
TI  - Body mass index and risk of stroke mortality among a random sample of Japanese
      adults: 19-year follow-up of NIPPON DATA80.
AB  - BACKGROUND: The relationship between body mass index (BMI) and stroke mortality
      remains unclear. The aim of the present study was to elucidate the relationship
      between BMI and stroke death in a representative cohort of Japanese men and
      women. METHODS: We analyzed a database of 9,526 men and women aged 30 years and
      older who were randomly selected throughout Japan in 1980. These individuals had
      no history of stroke and were followed for 19 years. Hazard ratios (HR) and their
      95% confidence intervals (CI) of deaths due to total stroke, cerebral infarction,
      and intracerebral hemorrhage were examined using Cox's proportional hazards
      regression models of BMI levels. RESULTS: A U-shaped association between BMI and
      cerebral infarction mortality was observed. Participants with the highest BMI
      category (BMI > or = 30.0) showed a significantly highest HR for cerebral
      infarction (HR 2.46, 95% CI 1.01-5.99). The excess risk at the lower extreme of
      the BMI was confined to men. These associations did not change after excluding
      deaths occurring in the first 2 years of follow-up. CONCLUSIONS: In the Japanese
      general population, a U-shaped association between BMI and cerebral infarction
      mortality was found and the excess risk at the lower extreme of the BMI was
      confined to men.

PMID- 16888383
TI  - Effect of carotid artery stenting on ocular circulation and chronic ocular
      ischemic syndrome.
AB  - BACKGROUND: The authors evaluated the effect of carotid artery stenting (CAS) on
      ocular circulation and chronic ocular ischemic syndrome. METHODS: We examined 38
      patients with carotid artery stenosis (>80%) at its origin treated with CAS.
      Ocular circulation and symptoms were examined before, within 24 h, and 1 week, 1
      month, and 3 months after CAS based on ophthalmic artery color Doppler flow
      imaging and ophthalmological examinations. RESULTS: Ocular circulation: Before
      CAS, 13 patients showed reversed ophthalmic artery flow, and 25 antegrade flow.
      Average peak systolic flow velocity was -0.038 m/s. Within 24 h after CAS, all
      patients showed antegrade ophthalmic artery flow; reversed flow before CAS was
      thus resolved. Average peak systolic flow velocity rose significantly to 0.36 m/s
      (p < 0.05). One week, 1 month and 3 months after CAS, there were no significant
      changes compared to the findings at 1 week after CAS. Ocular symptoms: Before
      CAS, 8 patients showed chronic ocular ischemic syndrome. During the follow-up
      period (mean: 2.8 years), the visual acuity improved in 7 cases. Average retinal
      artery pressure and arm-to-retina circulation time improved significantly to the
      normal level (p < 0.05). The other 30 patients complained of recurrent and
      worsened visual symptoms during the follow-up period. CONCLUSION: CAS was
      effective in improving ocular circulation, and also improved the chronic ocular
      ischemic syndrome caused by the severe carotid artery stenosis.

PMID- 16888385
TI  - Usefulness of MRI to demonstrate the mechanisms of myocardial ischemia in
      hypertrophic cardiomyopathy with myocardial bridge.
AB  - We present a case of symptomatic primary hypertrophic cardiomyopathy (HCM)
      associated with myocardial bridging of the left anterior descending (LAD) artery
      and suspected ischemia that could be related either to LAD artery compression or
      to microvascular perfusion abnormalities. MRI demonstrated the morphological
      appearance of myocardial hypertrophy, and coronary MR angiography evidenced the
      myocardial bridge and its functional consequences with stress MR perfusion. In
      conclusion, as a non-invasive comprehensive imaging technique, MRI should be
      considered in identifying the mechanisms of myocardial ischemia in HCM with
      myocardial bridge.

PMID- 16888386
TI  - Incident dementia cases and mortality. Results of the leipzig Longitudinal Study
      of the Aged (LEILA75+).
AB  - Mortality caused by dementia has mainly been examined in population-based studies
      relying on prevalent cases. This study aims to investigate the impact of incident
      dementia on mortality as well as to identify factors influencing the course of
      dementia and those predicting early death in demented individuals. A
      representative community sample of 1,692 individuals aged 75 years and over was
      examined by neuropsychological testing in a four-wave study. Data were analyzed
      with the Cox proportional hazards model after making necessary adjustments for
      potential covariates. At the third follow-up 51% of the incident demented and 19%
      of the participants without dementia had died. The mean survival time was 3.1
      years (95% CI = 2.8-3.4) for the demented subjects and 4.0 years (95% CI = 3.9
      4.0) for those without dementia (p < 0.001). In the total sample, the relative
      risk of dying after developing dementia was estimated to be 2.4 (95% CI = 1.6
      3.6) with age, sex, education, co-morbidity, and institutionalization being taken
      into consideration. Those persons with incident dementia who died had a more
      severe dementia. Population-based studies relying on incident cases are
      especially valuable in describing course and outcome of dementia. Studies relying
      on prevalent cases and clinical samples tend to overestimate mortality and
      propose course-modifying factors that are challenged by studies relying on
      incident cases.

PMID- 16888387
TI  - Nutritional status as a risk factor in esophageal surgery.
AB  - BACKGROUND: Nutritional condition is one of the factors determining postoperative
      outcome in esophageal surgery. This study explored the relation between
      preoperative nutritional status and postoperative infectious complications.
      METHODS: From a prospective database, 400 patients who underwent esophageal
      resection for malignancy were selected. Preoperative nutritional status was
      assessed by body mass index, prognostic nutritional index (PNI), nutritional risk
      index (NRI) and weight loss. The association between nutritional parameters and
      postoperative complications and mortality, gender, age and hospitalization was
      assessed. RESULTS: PNI and NRI differed between the patients with and without
      postoperative infectious complications (p = 0.031 and p = 0.009, respectively).
      However, receiver operating characteristic curves showed that PNI and NRI have a
      low predictive value for such complications. Also, no associations were found
      between nutritional parameters and in-hospital mortality. Although mean
      nutritional parameters were significantly lower, i.e. worse, in patients with
      neoadjuvant treatment as compared to no such treatment, the incidence of
      complications did not significantly differ between these treatment groups.
      Although PNI and NRI correlated negatively with age, no association was found
      between age and infectious complications. Multivariate analysis of various
      factors showed the male gender to be the only significant risk factor for
      development of infectious complications. DISCUSSION: Preoperative nutritional
      status established by PNI, NRI, body mass index and weight loss has limited value
      in predicting complications following esophageal resection.

PMID- 16888388
TI  - Molecular mediators of alphavbeta3-induced endothelial cell survival.
AB  - The alphavbeta3 integrin interaction with the extracellular matrix (ECM) plays an
      essential role in inhibiting apoptosis in endothelial cells. We have recently
      shown that alphavbeta3 ligation on rat aortic endothelial cells (RAECs)
      specifically activates the transcription factor nuclear factor kappaB (NF-kappaB)
      and promotes cell survival. Inhibiting NF-kappaB nuclear translocation abolished
      the protective effect of alphavbeta3 ligands. Here, we report that ligation of
      alphavbeta3 by its ligand, osteopontin (OPN), induces the phosphorylation and
      activation of inhibitory kappa B kinase beta IKKbeta and promotes the specific
      degradation of inhibitory kappa Balpha (IkappaBalpha) in RAECs. Overexpression of
      a dominant negative (DN) IKKbeta protein prevents IkappaBalpha phosphorylation,
      NF-kappaB activation, and inhibits the protective effects of OPN. The NF-kappaB
      inducing kinase (NIK) has been shown to be one of the upstream kinases involved
      in IKK activation. OPN-mediated NF-kappaB activity is increased upon NIK wild
      type (WT) overexpression and blocked following NIK DN overexpression. In
      addition, NIK-/-mouse embryonic fibroblasts (MEFs) plated on OPN display reduced
      NF-kappaB activity and decreased IkappaBalpha phosphorylation compared to
      NIK+/+MEFs. Finally, functional inhibition of integrin beta3-dependent NF-kappaB
      signaling decreases OPN-induced IkappaBalpha, IKKbeta and NIK phosphorylation.
      These studies for the first time show that the alphavbeta3-NF-kappaB-dependent
      endothelial survival pathway is dependent on IkappaBalpha, IKKbeta, and NIK.

PMID- 16888389
TI  - Human obesity: its hormonal basis and the role of gastric inhibitory polypeptide.
AB  - Obesity is an abnormal expansion of the adipose organ and is a pathophysiological
      response to an imbalance between energy intake and energy expenditure. It is the
      result of a large number of diverse factors involving heritable and environmental
      characteristics. A simple definition of obesity is difficult and unsatisfactory
      and its age dependency has largely been ignored. Differentiation between healthy,
      age-related plumpness and obesity is often blurred and responsible for
      overdiagnosis of obesity in the developed world. In the past, epidemiological
      studies have often ignored the different prognostic significance of the two major
      phenotypes of human obesity making their conclusions of limited value. The role
      of heritable factors in determining both the propensity to develop obesity under
      favourable environmental conditions, including inactivity and unlimited access to
      fat-rich foods, and the phenotype it assumes received an enormous fillip from
      experiments involving genetically modified animals. The most important of these
      have demonstrated the key role played by a number of newly discovered or recently
      resurrected polypeptide hormones that are released from the intestine in response
      to food. Molecular manipulation of these hormones, especially of glucose
      dependent insulin-stimulatory polypeptide offers a new therapeutic approach.

PMID- 16888390
TI  - Risk factors of spontaneous pneumothorax in Kuwait.
AB  - OBJECTIVES: To determine the risk factors of spontaneous pneumothorax (SP) in
      Kuwait. SUBJECTS AND METHODS: From January 2002 through December 2003, 254
      consecutive cases with a diagnosis of SP were reviewed. Analyses of pneumothorax
      rates by age, sex, smoking, body mass index (BMI) and climatic conditions were
      evaluated. RESULTS: Of the 254 patients, 242 (95%) were male and 12 (5%) were
      female; a larger proportion of 180 (88%) were Kuwaitis and 74 (12%) were
      expatriates. Two hundred and eight (82%) episodes were regarded as primary SP and
      46 (18%) as secondary SP. The mean age was 24.5 +/- 5.8 years for primary SP and
      45.7 +/- 14.5 years for secondary SP. One hundred and ninety-six (77%)
      individuals were current smokers. BMI in primary and secondary SP was 19.3 and
      22.4, respectively (p < 0.001). There was no relationship between SP and climatic
      conditions (a rise or fall in temperature, humidity or atmospheric pressure).
      However, a slight increase in SP occurred in July, probably the hottest month in
      Kuwait. CONCLUSIONS: The data indicate that the most important risk factors of SP
      in Kuwait are smoking, low BMI and the male gender.

PMID- 16888391
TI  - Residual need for early orthodontic treatment and orthodontic treatment
      experience among 13- to 14-year-old school children in Kuwait.
AB  - OBJECTIVE: Our purpose was to determine the residual need for early orthodontic
      treatment and the parameters associated with orthodontic treatment experience in
      13- to 14-year-old school children in Kuwait. SUBJECTS AND METHODS: A total of
      788 boys and 795 girls, representing about 6.7% of the target population, were
      selected according to cluster sampling methods. Information on nationality,
      family income and orthodontic treatment experience was collected through subject
      and family interviews. The occlusal morphology was recorded in a well-lit
      classroom or from initial study models of subjects with orthodontic treatment
      experience. RESULTS: Only 6.7% of the 225 subjects with early treatment need,
      defined as overjet >or=6.5 mm, and functional posterior and anterior crossbite on
      1 or more teeth, had treatment experience. Residual need for early treatment was
      present in 13.4% of the subjects. Only 26.8% of the subjects with treatment
      experience met our criteria for early treatment need. The odds of treatment
      experience were higher in the subjects attending private schools (p < 0.05), in
      those from families with an income of KWD >2,000 (USD 6,600; p < 0.01) and in
      subjects meeting the criteria for early treatment need (p < 0.01). CONCLUSIONS:
      About 15% of each birth cohort of school children in Kuwait need early
      orthodontic treatment. Less than 10% of those with a need have treatment
      experience at 13-14 years of age, and about 75% of those with treatment
      experience at that age do not need early treatment. The predictors for treatment
      experience at 13-14 years of age are private-school attendance, a high family
      income and need for early treatment.

PMID- 16888392
TI  - Practice and opinion towards disposal of unused medication in Kuwait.
AB  - OBJECTIVES: The aim of this study was to measure the attitude and practice of
      Kuwaiti patients in Kuwait with regard to safe disposal of unwanted medicines.
      SUBJECTS AND METHODS: Three-hundred patients or their family members waiting for
      prescriptions at public general hospitals in Kuwait completed a questionnaire
      soliciting their practice with regard to medication use and disposal, and their
      opinion of the best way to dispose of unwanted medicines. RESULTS: Almost half of
      the respondents (45.4%) obtained medicines on prescription more than 3 times a
      year and almost all had unwanted medicines in the home. Reasons for possessing
      unused medication were mostly due to a change of medication by the doctor
      (48.9%), or self-discontinuation (25.8%). Their most common method of disposal
      was to throw unwanted medicines in the trash (76.5%) or flush them down the drain
      (11.2%). Half (54.0%) thought that a system of taking medicines to pharmacies for
      safe disposal would be favorable. CONCLUSION: The study indicates that the need
      for an appropriate method for disposal of unwanted medication exists in Kuwait.
      Hence, guidelines on safe disposal of unwanted medicines are required and an
      organized method of collecting unused medication needs to be introduced.

PMID- 16888393
TI  - Intravenous contrast media in uroradiology: evaluation of safety and tolerability
      in almost 50,000 patients.
AB  - OBJECTIVE: To evaluate the frequency of adverse events and possible risk factors
      after the administration of an intravenous contrast medium (CM), iobitridol, in a
      large multicentre postmarketing surveillance study. SUBJECTS AND METHODS: A total
      of 49,975 patients undergoing intravenous urography were included in this study.
      A water-soluble, non-ionic CM (iobitridol, 1 ml/kg body weight) was administered.
      Age, sex, indication for the actual examination and adverse events were
      documented. Also, high-risk patients were identified. RESULTS: Of the 49,975
      patients, 28,336 (56.7%) were males and 21,639 (43.3%) females. Indications for
      urography were mainly urolithiasis (39.1%), inflammatory diseases (25.6%) and
      tumours (13.9%). Additionally, 7.4% were risk patients: 1.9% with creatinine >1.5
      mg/dl (0.1% were on haemodialysis); 0.8% had a history of previous allergic
      reactions to CM, 3.7% pre-existing asthma or allergies and 2% other risk factors
      against CM examination. Only 0.9% of the patients experienced acute adverse
      events that were non-serious and transient. Less than 0.1% of the patients
      experienced vomiting, dizziness or cardiovascular problems. Only 1 patient
      developed an anaphylactic shock but recovered fully under treatment. A chi(2)
      analysis revealed that adverse reactions occurred in patients with pre-existing
      renal insufficiency or allergies. Significantly more females had contrast-agent
      related symptoms compared to men. Patients undergoing urography for urolithiasis
      had significantly fewer symptoms compared to patients with other indications.
      CONCLUSION: Iobitridol is clinically safe and well tolerated in urography as
      demonstrated in this study of a large patient population, producing mainly minor
      symptoms as adverse events. However, caution is advised when administering
      iobitridol to high-risk patients.

PMID- 16888394
TI  - Sociodemographic and clinical characteristics of patients with dissociative
      disorders in an Arabian society.
AB  - OBJECTIVE: The aim of the study was to determine the sociodemographic and
      clinical characteristics of patients with dissociative disorders among
      psychiatric patients in the population of the United Arab Emirates. SUBJECTS AND
      METHODS: Six hundred inpatients with dissociative disorders were approached
      during the period 1997-2003, and 468 agreed to participate in the study. These
      patients were recruited from Al-Ain and Tawam Teaching Hospitals and Al-Jahili
      Primary Health Care Centers in Al-Ain, United Arab Emirates. The study is based
      on a questionnaire that included sociodemographic and clinical variables.
      Dissociative disorders were diagnosed according to the classification set forth
      in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) and the
      International Classification of Diseases (ICD-10) of the World Health
      Organization. RESULTS: Of the 468 patients studied, the majority (67.9%) were
      young, under the age of 25 years; 55% were UAE nationals, 59.4% female and 40.6%
      male. Disorganized movement was significantly lower among females (34.2%) than
      males (44.2%, p < 0.03). Disapproving of the key relative behaviour was higher in
      females (24.1%) compared to males (13.2%); comorbid anxiety was higher in females
      (37.4%) vs. males (25.3%). Disturbed relationships were more common in females
      (40.3%) while precipitating factors, such as intolerable stressful events, were
      significantly higher in males (42.6%, p < 0.01). Furthermore, males (20.5%) had a
      significantly higher history of similar episodes and other psychiatric illnesses
      (7.5%) than females. Finally, females (41%) showed more statistically significant
      improvements compared to males (29.5%, p < 0.001). CONCLUSION: Patients under 25
      years of age suffered more from dissociative disorders with no correlation to
      educational level as a predisposing factor. The most common symptoms were fits or
      unorganized movements.

PMID- 16888395
TI  - Evidence of occult hepatitis B virus infection among Omani blood donors: a
      preliminary study.
AB  - OBJECTIVES: The aim of this study was to determine the prevalence of hepatitis B
      surface antigen (HBsAg), hepatitis B core antibodies (anti-HBc) and hepatitis B
      virus (HBV) DNA among a selected group of Omani blood donors. MATERIALS AND
      METHODS: Two hundred HBsAg-negative donors were screened for anti-HBc. Those
      found to be positive were investigated for HBV DNA by polymerase chain reaction.
      HBsAg was retested on these sera following an immune complex dissociation
      technique. RESULTS: HBsAg was present in 2.8% of the donors. Forty-one out of 200
      (20.5%) HBsAg-negative donors were positive for anti-HBc. Eleven were positive
      for HBsAg after dissociation, whereas 8 gave readings just over the cutoff. HBV
      DNA was not detected in this group. CONCLUSION: Findings indicate that testing
      donors for HBsAg alone is not sufficient to eliminate HBV from the blood supply
      in Oman.

PMID- 16888396
TI  - Determination of berberine content in the stem extracts of Coscinium fenestratum
      by TLC densitometry.
AB  - OBJECTIVE: To develop the optimal extraction procedure (i.e. maceration,
      percolation or Soxhlet extraction) and thin- layer chromatographic (TLC)
      densitometric method for the determination of berberine content of Coscinium
      fenestratum. MATERIALS AND METHODS: Maceration, percolation and Soxhlet
      extraction techniques were used to extract alkaloids from dried stems of C.
      fenestratum. The solvents used were 50 and 80% ethanol. Crude extracts and
      berberine content recovered from the TLC fingerprint were evaluated for chemical
      components of each extraction method. Precoated silica gel GF(254) plates were
      used as stationary phase while butanol:glacial acetic acid:water (14:3:4) was
      used as a mobile phase. Detection and quantitation of berberine were performed by
      densitometry at the wavelength of 415 nm over the linearity range of 240-840 ng
      (r(2) = 0.9982). The relative standard deviations from intraday and interday
      precisions were less than 4.13%. RESULTS: The recovery of standard berberine was
      97.58-98.71% (%RSD = 3.85), and the limit of detection and quantitation were 25
      and 50 ng/spot, respectively. Eighty percent ethanol gave a higher content of
      berberine than 50% ethanol. Berberine contents from maceration, percolation and
      Soxhlet extraction with 80% ethanol were 3.37+/- 0.30, 3.08+/- 0.38 and 2.67+/-
      0.27% w/w, respectively. CONCLUSION: The TLC-densitometric method was simple,
      accurate and precise for quantitating berberine in the stem extract of C.
      fenestratum. Maceration with 80% ethanol gave the highest content of berberine in
      the extract. TLC of the extracts from different methods showed a similar pattern.

PMID- 16888397
TI  - Agenesis of the gallbladder with primary choledochal stones.
AB  - OBJECTIVE: To report a case of true agenesis of the gallbladder (GB) with
      obstructive jaundice due to primary choledochal stone. CLINICAL PRESENTATION AND
      INTERVENTION: A 66-year-old woman presented with a full picture of obstructive
      jaundice, both clinically and biochemically. Ultrasound and endoscopic retrograde
      cholangiopancreatography failed to show the GB but showed dilatation of
      extrahepatic ducts with a stone in the common bile duct (CBD). Upon exploration,
      the GB was found to be absent and through a choledochotomy, the stone in the CBD
      was removed. CONCLUSION: This case shows that proper exploratory laparotomy and
      intraoperative cholangiography may be required to confirm absence of the GB.

PMID- 16888398
TI  - Tuberculosis of the greater trochanter. Report of four cases.
AB  - OBJECTIVE: To present four cases of tuberculosis of the greater trochanter. CASE
      PRESENTATION AND INTERVENTION: The four cases (3 females and 1 male), aged 45-70
      years, presented with mechanical pain in the trochanteric area associated with
      progressive swelling in the 3 female patients in whom mobility was also
      restricted. X-ray revealed a mass in 2 females; CT scan and MRI exhibited an
      abscess in the 3 females. Histological and bacteriological examinations showed
      Mycobacterium bovis in the 3 females and M. tuberculosis in the male. In the
      females, tritherapy and surgery were performed, while in the male quadritherapy
      and surgery. All the patients recovered and were followed up for 4-9 years.
      CONCLUSION: These cases show that both chemotherapy and surgery must be synergic
      if tuberculosis is diagnosed and an abscess is confirmed by imaging.

PMID- 16888400
TI  - Cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy: an imaging mimic of multiple sclerosis. A report of two
      cases.
AB  - OBJECTIVE AND IMPORTANCE: To describe the imaging findings of two cases of
      cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy (CADASIL) mimicking multiple sclerosis. CLINICAL PRESENTATION
      AND INTERVENTION: Two cases presenting with neurological signs and symptoms were
      referred for magnetic resonance imaging (MRI) evaluation of the brain. Case 1 was
      a 36-year-old female patient presenting with recurrent headaches and recent onset
      numbness in the fingers of the right hand. Neurological examination showed a mild
      sensory deficit in the right hand. Case 2 was a 31-year-old female patient
      presenting with attacks of right-sided numbness of the face and body. The
      neurological examination revealed a sensory loss in the face and brisk deep
      tendon reflexes. Routine MRI sequences showed two types of lesions in both cases:
      'punctate' hyperintense lesions on T(2)-weighted images (T(2)WI)/fluid-attenuated
      inversion recovery (FLAIR) images, hypointense on T(1)-weighted images (T(1)WI)
      and 'diffuse' white matter lesions, hyperintense on T(2)WI/FLAIR sequences and
      isointense to hypointense on T(1)WI. All lesions showed no contrast enhancement.
      Both cases were previously clinically and radiologically diagnosed as multiple
      sclerosis. There was a strong family history consistent with recurrent
      infarctions in other family members of both patients. Both cases were later
      diagnosed as CADASIL by skin biopsy/genetic linkage studies and follow-up.
      CONCLUSION: The cases showed that CADASIL causes stroke-like episodes in adults
      and can mimic multiple sclerosis on imaging. Clinical evaluation and MRI findings
      allow a differentiation of the two entities.

PMID- 16888399
TI  - Osteochondroma of the scapula associated with winging and large bursa formation.
AB  - OBJECTIVE: To report a case of scapular osteochondroma associated with pain and
      winging that is rarely reported in the medical literature. CASE PRESENTATION AND
      IDENTIFICATION: A 19-year-old male presented with pain and winging of the right
      scapula. CT scan revealed an osteochondroma of the medial border of the scapula
      with a large bursa between the chest wall and the tumour. Excision of the tumour
      relieved the symptoms. Pathological study showed osteochondroma of the scapula.
      In a follow-up 1 year later he was free of pain with no clinical or radiological
      sign of recurrence. CONCLUSION: A case of scapular osteochondroma associated with
      pain and winging treated by excision and follow-up showed no sign of clinical or
      radiological recurrence.

PMID- 16888401
TI  - Carotid body tumors and adrenal pheochromocytomas in siblings of a Turkish
      family.
AB  - OBJECTIVE: This is a report of 2 hypertensive siblings with a history of carotid
      body tumors and subsequent benign adrenal pheochromocytomas (pheos) in a family
      where the mother had died of possible adrenal carcinoma. CLINICAL PRESENTATION
      AND INTERVENTION: The first case was a 35-year-old woman with paroxysmal
      hypertensive attacks and a right adrenal mass. She had earlier undergone surgery
      to remove bilateral carotid body tumors. Investigation revealed excessive
      excretion of catecholamines and their metabolites in the urine. Abdominal MRI and
      (131)I-MIBG scintigraphy revealed a right adrenal tumor. Right adrenalectomy was
      performed. The second case, the 45-year-old brother of the first case, was found
      to have a left adrenal mass on abdominal MRI. Catecholamines and their
      metabolites in the urine were found to be increased. He had also had surgery to
      remove bilateral carotid body tumors of the neck. Left adrenalectomy was
      performed. Both siblings showed no evidence of other familial syndromes, such as
      multiple neoplasia type 2, von Hippel-Lindau disease or neurofibromatosis type 1.
      CONCLUSION: Although the combination of familial carotid body tumors and pheo is
      rare, a patient who remains hypertensive after removal of a carotid body tumor
      deserves a careful evaluation to exclude pheo. Such tumors may be extra-adrenal
      or multifocal.

PMID- 16888402
TI  - Long-term in vitro growth of human insulin-secreting insulinoma cells.
AB  - OBJECTIVE: Long-term in vitro maintenance of human insulin-secreting insulinoma
      cells. METHODS: (1) Cell culture of ex vivo-derived insulinoma cell suspensions
      from 8 individual human donors, using various cell culture medium
      supplementations; (2) determination of insulin synthesis and secretion using
      immunocytochemistry and insulin and pro-insulin radioimmunoassays; (3) nestin
      immunostaining of long-term in vitro grown insulinoma cell suspensions, and (4)
      phase-contrast light microscopy for analyzing the in vitro growth characteristics
      of the insulinoma cells. RESULTS: (1) Parallel persistence of in vitro insulinoma
      cell proliferation as well as insulin-synthesizing and -secreting capacity
      depended on both the co-culture of insulinoma cells with human fibroblasts and
      the supplementation of the cell culture medium with tissue culture supernatant
      derived from the rodent pituitary adenoma cell line GH-3; (2) immunostaining for
      insulin and secretagogin confirmed the neuroendocrine origin of the insulinoma
      cells grown in vitro; (3) insulin secretion capability persisted up to an
      observation period of 25 weeks; (4) insulin secretion rates after 6 weeks of in
      vitro growth ranged from 3.5 to 83.3 muU/ml/h/60,000 cells plated, and (5) after
      long-term in vitro growth of insulinoma-derived cell suspensions with persistent
      insulin-secreting capacity, nestin staining was observed predominantly in co
      cultured fibroblasts. CONCLUSION: Our data describe for the first time the long
      term in vitro culture of insulin-secreting human insulinomas and highlight the
      importance of beta-cell trophic factors for insulinoma cell growth.

PMID- 16888403
TI  - Inhalation of low-level formaldehyde increases the Bcl-2/Bax expression ratio in
      the hippocampus of immunologically sensitized mice.
AB  - OBJECTIVE: A recent study from our research group showed that repeated exposure
      to low-level formaldehyde (FA) increases the production of nerve growth factor,
      involving the survival and maintenance of neurons, in the hippocampus of
      immunized mice. In the present study, we examined the effects of FA on apoptotic
      mechanisms regulating survival and death of cells and on N-methyl-D-aspartate
      (NMDA) receptors related to hippocampal functions in the mouse hippocampus.
      METHODS: Western blot analyses were performed for Bcl-2, Bax and NMDA receptor
      subtypes 2A and 2B of the hippocampus taken from C3H mice exposed to 0 or 400 ppb
      of FA with or without ovalbumin (OVA) immunization. Immunohistochemical analysis
      for active caspase-3 was also carried out for these mice. RESULTS: The ratio of
      Bcl-2 to Bax expression levels significantly increased with 400-ppb FA exposure
      in OVA-immunized mice but not in mice without OVA immunization, although
      differences in each protein level were not significant among groups. Active
      caspase- 3-immunoreactive cells were found in the hippocampus. However, the
      number was only a few and not significantly affected by FA exposure and OVA
      immunization. NMDA receptor type 2A and 2B expression levels of FA-exposed mice
      were sustained at comparative levels with those for the control mice with or
      without OVA immunization. CONCLUSIONS: These results indicate that changes in the
      Bcl-2/Bax expression ratio, which occurs with low-level FA exposure and
      immunization and may follow enhancement of nerve growth factor production, exerts
      a protective effect against cell death by apoptosis.

PMID- 16888404
TI  - Spatially filtered magnetoencephalographic analysis of cortical oscillatory
      changes in basic brain rhythms during the Japanese 'Shiritori' Word Generation
      Task.
AB  - BACKGROUND: 'Shiritori' (capping verses) is a traditional Japanese word
      generation game, and is very familiar to native Japanese speakers. The shiritori
      task is expected to more strongly activate temporal language-related regions than
      conventional word generation to letters because of its characteristic way to make
      cue letters. OBJECTIVES: The aim of this study was to examine the cortical
      oscillatory changes in basic brain rhythms during silently performing a shiritori
      task. METHODS: Using synthetic aperture magnetometry (SAM) analysis of
      magnetoencephalography, we estimated the tomographic distributions of the
      statistically significant differences of the power in the alpha and beta
      frequency bands between the resting and the task periods. RESULTS: Significant
      event-related desynchronization (ERD) in the 8- to 25-Hz band, thought to reflect
      neural activation, was localized within task-related cortical regions with left
      side dominance. The significant ERDs were estimated in both the frontal and
      temporal language-related regions encompassing Broca's and Wernicke's areas,
      although previous neuroimaging studies using word generation to letters showed
      neural activation predominantly in frontal regions. CONCLUSIONS: Our results show
      the potential of SAM analysis for reliable brain mapping of language processing,
      and suggest that the shiritori task might be more suitable for examining the
      language-related network in the brain than conventional word generation to
      letters.

PMID- 16888405
TI  - Facilitated beam-walking recovery during acute phase by kynurenic acid treatment
      in a rat model of photochemically induced thrombosis causing focal cerebral
      ischemia.
AB  - We previously demonstrated the presence of activated areas in the non-injured
      contralateral sensorimotor cortex in addition to the ipsilateral sensorimotor
      cortex of the area surrounding a brain infarction, using a rat model of focal
      photochemically induced thrombosis (PIT) and functional magnetic resonance
      imaging. Using this model, we next applied gene expression profiling to screen
      key molecules upregulated in the activated area. RNA was extracted from the
      ipsilateral and contralateral sensorimotor cortex to the focal brain infarction
      and from the sham controlled cortex, and hybridized to gene-expression profiling
      arrays containing 1,322 neurology-related genes. Results showed that glycine
      receptors were upregulated in both the ipsilateral and contralateral cortex to
      the focal ischemic lesion. To prove the preclinical significance of upregulated
      glycine receptors, kynurenic acid, an endogenous antagonist to glycine receptors
      on neuronal cells, was administered intrathecally. As a result, the kynurenic
      acid significantly improved behavioral recovery within 10 days from paralysis
      induced by the focal PIT (p < 0.0001), as evaluated with beam walking. These
      results suggest that intrathecal administration of a glycine receptor antagonist
      may facilitate behavioral recovery during the acute phase after brain infarction.

PMID- 16888407
TI  - Combined proton beam radiotherapy and transpupillary thermotherapy for large
      uveal melanomas: a randomized study of 151 patients.
AB  - INTRODUCTION: Exudation from the tumour scar and glaucoma can be major problems
      after proton beam irradiation of uveal melanoma and can sometimes lead to
      secondary enucleation. We conducted a randomized study to determine whether
      systematic transpupillary thermotherapy (TTT) after proton beam radiotherapy
      could have a beneficial effect. PATIENTS AND METHOD: Between February 1999 and
      April 2003, all the patients treated by proton beam radiotherapy for uveal
      melanomas >/=7 mm thick or >/=15 mm in diameter were included in this study after
      giving their informed consent. One half of the patients received proton beam
      radiotherapy alone (60 Gy in 4 fractions) and the other half received the same
      dose of proton beam radiotherapy followed by TTT at 1, 6 and 12 months. All the
      information concerning the initial tumour parameters, treatments and follow-up
      was recorded and a statistical analysis was performed. RESULTS: We randomized 151
      patients. The median follow-up was 38 months. The 2 groups of patients were
      similar in terms of age, gender and tumour characteristics. The patients treated
      with TTT showed a greater reduction of tumour thickness (p = 0.06), less retinal
      detachment at the latest follow-up (p = 0.14) and a lower secondary enucleation
      rate (p = 0.02). DISCUSSION: The present study is the first randomized analysis
      to demonstrate a significant decrease in the secondary enucleation rate in
      patients treated with TTT after proton beam radiotherapy. Further studies should
      be performed to determine whether TTT could be beneficial to smaller tumours and
      to define its optimal dose.

PMID- 16888408
TI  - Lentiviral vector-mediated downregulation of ornithine decarboxylase inhibits
      tumor cell growth in vitro and in vivo.
AB  - Ornithine decarboxylase (ODC), a molecule that is overexpressed in various
      cancers, has been associated with cell growth and proliferation. Downregulation
      of ODC may inhibit tumor cell growth. To verify this hypothesis, ODC gene
      silencing was studied in colorectal cancer cells in vitro and in vivo. A
      lentiviral system harboring both enhanced green fluorescent protein reporter gene
      and the ODC short hairpin RNA expression cassette was firstly constructed. Then
      the stable ODC gene silencing cell lines HT29/ODC and LoVo/ODC were established
      and their growth-inhibiting characteristics were identified. Real-time RT-PCR
      analysis of mRNA and Western blot analysis of proteins were used to evaluate the
      expression of the ODC gene. In the cells studied, ODC expression was
      significantly decreased. Proliferation of HT29/ODC and LoVo/ODC cells was
      obviously retarded. In animal experiments, HT29/ODC and LoVo/ODC cell xenografts
      demonstrated growth suppression compared to parental or control colorectal cancer
      cell xenografts. The results demonstrated that lentiviral vector was capable of
      downregulating ODC, resulting in impressive anticancer effects. It offers a
      powerful new strategy for cancer gene therapy and may be useful in the control of
      solid tumors, such as human colorectal carcinomas.

PMID- 16888406
TI  - Targeting pericytes diminishes neovascularization in orthotopic uveal melanoma in
      nerve/glial antigen 2 proteoglycan knockout mouse.
AB  - In this investigation, we explored whether knockout of nerve/glial antigen 2
      (NG2), a pericyte component, inhibited neovascularization and growth of uveal
      melanoma xenografts. For this, we used multichannel laser scanning confocal
      microscopy and quantitative image analysis. Orthotopic human uveal melanoma (OCM
      1A) xenografts were induced in NG2 knockout and wild-type mice, which were
      immunosuppressed with cyclosporin A. Inhibition of pericytes through NG2
      proteoglycan decreased neovascularization and tumor end volume, rendering
      pericytes and NG2 proteoglycan potential cellular and molecular therapeutic
      targets in uveal melanoma.

PMID- 16888409
TI  - Expression of tumor-associated differentially expressed Gene-14 (TADG-14/KLK8)
      and its protein hK8 in uterine endometria and endometrial carcinomas.
AB  - To clarify the biological behavior of TADG-14/KLK8, we investigated TADG-14/KLK8
      mRNA by semiquantitative RT-PCR and hK8 expression by immunohistochemistry using
      37 normal endometria and 44 endometrial carcinoma tissues. TADG-14/KLK8 mRNA
      expression levels were significantly higher in proliferative compared to
      secretory phase endometria (p = 0.0143). Levels of TADG-14/KLK8 mRNA expression
      correlated with hK8 protein levels. hK8 was detected in 73.3% (11/15) of
      endometria with a significantly higher detection rate in the proliferative
      compared to secretory and atrophic phase endometria (p = 0.0002). High expression
      of hK8 was found in 61.4% of endometrial carcinomas compared to 35.1% of
      endometrial tissue samples (p = 0.0187). hK8 expression was significantly higher
      in stage I (p = 0.0433, 0.0038) and grade 1/2 (G1/2) of the tumors (p = 0.0195,
      0.0044). We suggest that expression of TADG-14/KLK8may be regulated by sex
      steroid hormones in endometria. Our results indicate that elevated TADG-14/KLK8
      expression is an early event in endometrial carcinogenesis, and may potentially
      serve as a useful early biomarker for the detection of endometrial carcinomas in
      menopausal women.

PMID- 16888410
TI  - Renal injury: 5-year experience and literature review.
AB  - INTRODUCTION: Appropriate management of renal trauma is controversial. The
      purpose of this study is to present our 5-year experience in renal trauma and
      review the literature. MATERIALS AND METHODS: From 1999 to 2003, 28 patients were
      identified with renal injuries. 25 (89.3%) of the injuries were caused by blunt
      trauma, 2 (7.1%) by stab wounds, and 1 (3.6%) by gunshot wound. Methods for
      diagnosis included ultrasonography (US), computed tomography (CT), diagnostic
      peritoneal lavage (DPL), combinations of more than one technique or no one of
      them. The English-language literature about renal trauma was also identified
      using Medline, and additional cited works not detected in the initial search
      obtained. RESULTS: 18 patients underwent immediate or during 24 h operation;
      while 5 nephrectomies were performed. 11 patients with grade I to III injuries
      were selected for nonoperative management of renal injuries. All complications
      were noted and studied according to the initial therapeutic management and grade.
      Follow-up was clinical and radiological. 3 postoperative deaths were observed.
      CONCLUSION: The goals of treatment of renal injuries include accurate staging and
      minimal complications. Surgery can be avoided in most cases of blunt renal injury
      but there is also a trend towards conservative management of penetrating trauma.
      Nephrectomy is associated with high-grade renal injuries, while minor renal
      injuries can safely be managed conservatively.

PMID- 16888411
TI  - Modified extravesical ureteroneocystostomy for completely duplicated ureters in
      renal transplantation.
AB  - INTRODUCTION: Completely duplicated ureters are the most common congenital
      malformation of the upper urinary tract. However, there are very few reports on
      transplantation using kidneys with double ureters, and the technique of
      ureterocystoneostomy for completely duplicated ureters has not yet been
      established. PATIENTS AND METHODS: We treated 3 patients with completely
      duplicated ureters at our institutions from January 1998 to October 2005. We
      modified the extravesical technique for treating these 3 cases and evaluated the
      52-month follow-up period for possible urological complications. RESULTS: Neither
      urological complications nor urinary tract infections occurred in the follow-up
      period after using our new technique. CONCLUSION: We conclude that this technique
      is an appropriate procedure for the transplantation of kidneys with completely
      duplicated ureters.

PMID- 16888412
TI  - CD10 expression in urothelial bladder carcinomas: a pilot study.
AB  - OBJECTIVES: The aims of this study were to investigate the expression of CD10 in
      normal bladder tissue and urothelial bladder carcinomas and to clarify its
      association with histopathological variables. MATERIALS AND METHODS: A total of
      79 urothelial bladder carcinomas were selected from routine archival material.
      All cases were reevaluated histopathologically and graded according to the World
      Health Organization (WHO) 1973, WHO/ISUP 1998, and WHO 1999 systems. The TNM
      system was used for their pathological staging. CD10 immunohistochemical staining
      was performed in selected slides. RESULTS: Tumoral cases consisted of 74 men
      (93.7%) and 5 women (6.3%). According to the pathological stage, 25 (31.6%), 33
      (41.8%), and 21 (26.6%) cases had pTa, pT1, and pT2-3 carcinomas, respectively.
      34 of 79 (43%) urothelial carcinomas and only 1 of 11 (9.1%) nontumoral cases
      showed positive CD10 immunostaining. It was a cytoplasmic diffuse or granular
      immunostaining pattern both in nontumoral and tumoral urothelia. There was no
      statistically significant difference between tumoral and nontumoral cases with
      respect to CD10 reactivity (p = 0.051), but there was a trend toward
      significance. In urothelial tumors, there was a significant inverse correlation
      between pathological stages and CD10 immunoreactivity (p = 0.036, r = -0,237).
      There was also a statistically significant difference between pTa and pT2-3
      urothelial tumors in relation to the CD10 expression (p = 0.034). No association
      was detected between CD10 expression and grades according to all systems used (p
      > 0.05). CONCLUSIONS: According to our findings, the CD10 expression in
      noninvasive carcinomas showed a higher level than that in invasive carcinomas,
      and it is inversely correlated with the pathological stage. CD10 may play an
      important role in the progression of urothelial bladder carcinomas, and
      downregulation probably facilitates invasion, especially muscle invasion.

PMID- 16888413
TI  - Adolescent varicocele: association with somatometric parameters.
AB  - INTRODUCTION: The developmental changes that occur as a result of puberty have
      been hypothesized to be important causes of varicocele. Various somatometric
      parameters were known to affect the occurrence of varicocele during the growth
      period. We conducted this study in order to examine these relationships and to
      determine the incidence of varicocele in adolescent males. PATIENTS AND METHODS:
      We evaluated 1,200 healthy males aged 0-19 years for varicocele and correlated it
      with the following somatometric parameters: age, height, body mass index (BMI),
      pubic hair distribution, penile length and testicular volume. RESULTS: Adolescent
      varicocele was found in 5.6% of the participants. The 13- to 19-year age-group
      had the highest incidence of varicocele (10.5%). Logistic regression analysis
      showed that the incidence was positively correlated with age, height and penile
      length (odds ratio 1.61, 1.04 and 1.37, respectively) and negatively correlated
      with left testicular volume, BMI and pubic hair distribution (odds ratio 0.87,
      0.87 and 0.47, respectively). CONCLUSION: Varicocele was more prevalent in tall
      boys with a lower BMI, who had quickly progressed through puberty. Our
      observations suggest that varicocele is associated with various somatometric
      parameters.

PMID- 16888414
TI  - Is laparoscopic approach safe for ectopic pelvic kidneys?
AB  - OBJECTIVE: To assess the feasibility and safety of a laparoscopic approach to
      pelvic kidneys for ablative and reconstructive surgery. METHODS: Between January
      2002 and February 2005, 6 patients with a left pelvic kidney; 2 with
      ureteropelvic junction obstruction, 2 with nonfunctioning kidney and 2 with
      pelvic stones were selected. These patients underwent dismembered pyeloplasty,
      simple nephrectomy and pyelolithotomy by laparoscopic approach. For pyeloplasty,
      omitting the prior retrograde stent facilitated dissection around the pelvis,
      which was identified first and then the ureter was traced downwards. Dismembered
      pyeloplasty was done by continuous sutures using 4-0 vicryl over a double-J stent
      placed antegradely. During nephrectomy, the ureter was identified over the iliac
      vessels and divided first. Subsequent dissection was carried out after lifting
      the kidney to identify ectopic renal vessels. Pyelolithotomy was performed for a
      large single pelvic stone after placing the ureteric catheter and confirming the
      stone's position by fluoroscopy. RESULTS: One patient with pyelolithotomy was
      converted to open surgery while the others were completed laparoscopically. Mean
      hospital stay was 4.16 (range 3-5) days, blood loss 115 (range 30-300) ml and
      mean operative time was 170 (range 140-220) min. There were no post-operative
      complications. After pyeloplasty there was significant improvement in renal
      function and drainage pattern on diuretic scan at 11 and 12 months. CONCLUSION:
      The laparoscopic approach provides all the benefits of a minimally invasive
      procedure to the patients. Due to the different locations of renal vessels, it is
      safe to approach the ureter first when performing nephrectomy. When performing
      pyeloplasty, omitting the prior stent placement helps in the identification and
      dissection of the renal pelvis.

PMID- 16888415
TI  - The limited significance of a longer duration of neoadjuvant hormonal therapy
      prior to radical prostatectomy for high-risk prostate cancer in Japanese men.
AB  - INTRODUCTION: The objective of this study was to evaluate the therapeutic
      significance of a longer duration of neoadjuvant hormonal therapy (NHT) followed
      by radical prostatectomy (RP) in Japanese men with high-risk prostate cancer.
      MATERIALS AND METHODS: This study included a total of 42 patients with high-risk
      prostate cancer who were treated with NHT for >or=8 months prior to RP. In this
      series high-risk prostate cancer was defined as clinical stage T2c or T3,
      pretreatment serum prostate-specific antigen (PSA) >20 ng/ml and/or a biopsy
      Gleason score of 8-10. Biochemical recurrence was defined as a serum PSA level of
      >or=0.2 ng/ml. The data of these patients were retrospectively reviewed to
      clarify the relationships between treatment outcomes and various
      clinicopathological parameters. RESULTS: The clinical stage was T2c in 13
      patients and T3 in 29, the median value of pretreatment serum PSA was 43.3 ng/ml
      (range 9.7-322.2), and the biopsy Gleason score was 6 in 3 patients, 7 in 16 and
      >or=8 in 23. Following NHT (median 12 months, range 8-27), the median value of
      serum PSA decreased to 0.05 ng/ml (<0.01-18.3 ng/ml), and 15 patients (35.7%)
      were pathologically downstaged. During the median follow-up of 38 months (range 8
      58), 11 patients (26.2%) developed biochemical recurrence, and the multivariate
      analysis identified pretreatment serum PSA, biopsy Gleason score and percentage
      of positive biopsy core as independent predictors of biochemical recurrence. The
      3-year biochemical recurrence-free survival rate of the 42 patients was 68.3%,
      which was not significantly different from that of 34 patients who underwent RP
      for high-risk prostate cancer without NHT during the same period. CONCLUSION: A
      longer duration of NHT followed by RP for patients with high-risk prostate cancer
      resulted in a comparatively favorable outcome. However, despite the nonrandomized
      retrospective analysis, the present findings suggest no significant impact of
      long-term NHT on biochemical recurrence. Longer follow-up is needed to determine
      whether this therapeutic strategy is beneficial for high-risk prostate cancer
      patients.

PMID- 16888416
TI  - Systemic inflammatory response, prostate-specific antigen and survival in
      patients with metastatic prostate cancer.
AB  - BACKGROUND: It is increasingly recognised that, in cancer patients, disease
      progression is dependent on a complex interaction of the tumour and the host
      inflammatory response and that the systemic inflammatory response, as evidenced
      by an elevated C-reactive protein (CRP) concentration, may be a useful prognostic
      factor. MATERIALS AND METHODS: The prognostic value of CRP compared with prostate
      specific antigen (PSA) was examined in 62 patients with metastatic prostate
      cancer receiving androgen-deprivation therapy. RESULTS: In all, 41 (66%) of
      patients died, 38 (61%) of their disease. On univariate survival analysis, PSA (p
      < 0.05) and CRP (p < 0.05) were significant predictors of cancer-specific
      survival. On multivariate analysis, both PSA (HR 1.96, 95% CI 1.00-3.83, p =
      0.049) and CR (HR 1.97, 95% CI 0.99-3.92, p = 0.052) were independent predictors
      of cancer-specific survival. PSA concentrations were significantly correlated
      with those of CRP (r(s) = 0.46, p < 0.001). CONCLUSION: The results of the
      present study suggest that, in patients with metastatic prostate cancer, the
      presence of an elevated CRP concentration predicts poor outcome, independent of
      PSA.

PMID- 16888417
TI  - Characterization of biochemical recurrence after radical prostatectomy.
AB  - BACKGROUND: This study sought to characterize the variables that predict
      postoperative prostate-specific antigen doubling time (PSADT) and biochemical
      recurrence time (RT) in patients who have failed radical prostatectomy (RP).
      METHODS: A total of 477 patients underwent RP at our institution for clinically
      localized prostate cancer. Of these patients, 64 (13.4%) demonstrated evidence of
      postoperative biochemical failure. PSADT and biochemical RT were calculated for
      all patients. PSADT and RT were correlated with clinical variables including
      preoperative PSA level, patient age, race, prostate weight and with pathologic
      characteristics of the operative specimen using uni- and multivariate analyses.
      In addition, PSADT and RT were also correlated with each other and with the time
      to postoperative adjuvant therapy. RESULTS: Median postoperative PSADT for
      patients who recurred after radical prostatectomy was 9.7 months. Postoperative
      PSADT was predicted by lymph node involvement (p < 0.001) and Gleason grade (p =
      0.06). Rapid PSADT also correlated with institution of postoperative adjuvant
      therapy (p = 0.003). Median biochemical RT for all patients was 6.7 months.
      Gleason grade and pathologic stage were found to be predictors of RT (p < 0.002).
      Postoperative PSADT did not correlate with RT (r = 0.08; p = 0.53). PSADT and RT
      were not different between Caucasian- versus African-Americans. CONCLUSIONS:
      These results serve to better characterize our cohort of patients who have
      evidence of biochemical recurrence after radical prostatectomy. Aggressiveness of
      recurrent disease (i.e. PSADT) seems to be predicted by lymph node involvement
      and higher pathologic grade. Furthermore, the lack of correlation of RT and PSADT
      suggests that early recurrences are not necessarily aggressive tumors:
      conversely, aggressive recurrences may occur at any point in the postoperative
      period. This information may aid in the postoperative treatment of recurrent
      disease and help to better define those patients who are at higher risk for
      developing clinical recurrence and who would benefit from greater vigilance
      during the postoperative period.

PMID- 16888418
TI  - Failure to maintain a suppressed level of serum testosterone during long-acting
      depot luteinizing hormone-releasing hormone agonist therapy in patients with
      advanced prostate cancer.
AB  - OBJECTIVES: It was the aim of this study to analyze the failure rates in
      achieving or maintaining castrate levels of serum testosterone in patients with
      advanced prostate cancer treated with the 3-month luteinizing hormone-releasing
      hormone agonist (LH-RH) therapy. METHODS: Total serum testosterone was determined
      in 234 patients with prostate cancer in a cross-sectional study. A subset of 90
      patients submitted to radical prostatectomy was used as the control group (group
      1), and 144 patients with advanced prostate cancer under androgen suppression
      therapy were included in the study group (groups 2 and 3). The study group was
      divided into 93 patients (group 2) treated with 50 mg daily bicalutamide and LH
      RH agonist (maximal androgen blockade, MAB) and 51 patients treated with the LH
      RH agonist alone (group 3). Median follow-up after androgen suppression was 42
      months. The castrate testosterone level was defined below 50 ng/dl. RESULTS: The
      mean serum testosterone level was 29.1 ng/dl in patients undergoing MAB (group 2)
      and 29.5 ng/dl in patients treated with the LH-RH agonist (group 3; p > 0.05). In
      group 1, the mean serum testosterone was 445.2 ng/dl (p < 0.0001). The rate of
      patients with a serum testosterone level higher than 50 ng/dl was 10.9% in
      patients undergoing androgen suppression, 10% in patients with MAB treatment and
      12.5% in those with LH-RH agonist therapy (p > 0.05). In group 1, 98.9% of the
      patients had a serum testosterone level higher than 50 ng/dl. CONCLUSIONS: A
      small but clinically significant rate of patients under 3-month LH-RH agonist
      therapy fail to achieve or maintain castrate testosterone serum levels. This
      finding supports the need of monitoring testicular response during LH-RH agonist
      therapy.

PMID- 16888419
TI  - Optimal nutrition should improve the outcome and costs of radical cystectomy.
AB  - INTRODUCTION: Nutritional support has been demonstrated to improve recovery from
      radical cystectomy, but is expensive and when used inappropriately may actually
      increase the costs and morbidity of surgery. We sought to establish national
      patterns of practice with regard to feeding following cystectomy in the UK. AIMS
      AND METHODS: Following consultation with the specialist nutrition team, a
      questionnaire was designed to investigate the feeding strategy after cystectomy
      and dispatched by post to all UK urologists. RESULTS: The majority (60%) of
      respondents employed a traditional strategy of resting the bowel and feeding
      orally after bowel recovery. A minority used either early total parenteral
      nutrition (TPN; 18.5%) or enteral nutrition (6.5%), but a larger proportion (29%)
      felt enteral nutrition was the 'optimal' feeding regime. Only 30% used guidelines
      and 52% felt trials would help to establish a nutrition strategy following
      cystectomy. CONCLUSION: There is little evidence that TPN improves the outcome of
      cystectomy and it may actually increase morbidity and costs, whereas enteral
      nutrition may improve recovery. Despite this evidence TPN is widely used by
      urologists whereas enteral nutrition is used infrequently. Implementation of an
      evidence-based feeding regime after cystectomy is likely to reduce the morbidity
      and financial costs of cystectomy.

PMID- 16888420
TI  - Comparison of transurethral resection and plasmakinetic transurethral resection
      applications with regard to fluid absorption amounts in benign prostate
      hyperplasia.
AB  - INTRODUCTION: We compare the absorption of irrigant fluid during gyrus
      plasmakinetic transurethral prostatectomy (PK-TURP) and transurethral resection
      of the prostate (TURP). PATIENTS AND METHODS: 42 patients with clinical benign
      prostatic hyperplasia were randomly assigned to undergo PK-TURP or TURP. In the
      PK-TURP group 0.9% NaCl was used as an irrigation fluid and 1.5% glycine in the
      TURP group. By adding ethanol to the irrigation fluids 1% ethanol-containing
      solutions were formed. All operations were carried out under spinal anesthesia
      and alcohol concentration of the ventilated air measurements were made just at
      the beginning of the operation, every 10 min peroperatively and at the end of the
      operation by using an alcoholmeter. RESULTS: There was no difference in age,
      prostate volume and the length of operation time in either group. In both groups,
      the estimated absorbed fluid volume increased with the duration of surgery (p <
      0.05). The difference between mean fluid absorption during PK-TURP and during
      TURP was the statistically significant (p < 0.01). CONCLUSION: PK-TURP operation
      causes lesser absorption of the irrigation fluid than the TURP operation. The
      lesser absorption of irrigation fluid and using saline instead of glycine
      decreases the risk of TUR syndrome.

PMID- 16888421
TI  - Operative failure during ureteroscopic pneumatic lithotripsy: factors affecting
      successful outcome.
AB  - AIM: We aimed to evaluate the predictive factors that would in turn indicate
      stone migration and the effects of these factors on the ultimate success of the
      intervention. METHOD: Patients were divided into two groups with respect to the
      migration of the stone treated. Group I: patients demonstrating stone migration
      during manipulation; group II: no migration of the stones noted. In the second
      phase of the study, the results of ureteroscopic management in 433 patients were
      evaluated with respect to the success rates obtained. Parameters such as stone
      size, stone burden, experience of the surgeon, length of the ureter proximal to
      the stone treated, and lastly transverse diameter of the ureter were noted in all
      patients as possible risk factors for stone migration. RESULTS: Statistical
      analysis of ureteroscopic success in all patients revealed that there was a
      meaningful correlation with respect to the length of the proximal ureteral
      portion (p < 0.0001) and surgeon's experience (p = 0.004). p value for the
      correlation between stone burden and operative success was 0.056. There was no
      significant correlation between stone size (p = 0.51), ureter diameter (p =
      0.78), and operative success. CONCLUSION: Stones that are close to the renal
      pelvis and treated by inexperienced physicians are the ones most likely to
      migrate to the renal pelvis during manipulation with pneumatic lithotripsy.

PMID- 16888422
TI  - Preliminary report of a multicentric study on environmental risk factors in Ta-T1
      transitional cell carcinoma of the bladder. A study from Gruppo Studi Tumori
      Urologici Foundation.
AB  - OBJECTIVE: The distribution of potential environmental risk factors among
      patients affected by superficial transitional cell carcinoma of the bladder
      (TCCB) has been analyzed. METHODS: Patients affected by superficial TCCB
      underwent TUR and early intravesical chemotherapy. Detailed data about age, sex,
      residence, employment, active and passive cigarette smoking, water resource and
      hair dye use were centralized. Analysis has been conducted on 474 patients
      affected by Ta-T1 G1-2 TCCB at medium risk for recurrence. Patients with primary
      single Ta G1-2, Tis or T1G3 tumors were excluded from the present analysis.
      RESULTS: Over 80% of the patients lived in urban areas, 22% were employed in
      industries presumed at risk for bladder cancer, 8% used hair dye and 75% were
      smokers. Bottled water was the only water resource in 42% of the patients.
      Employment in industry at risk (p = 0.01) and cigarette smoking (p = 0.04)
      resulted in being statistically related to tumor multiplicity. Moreover, the
      period of cigarette smoking was significantly longer in patients with recurrent
      tumors (p = 0.026). The municipal water supply represented the main water source
      in never-smokers (p = 0.01) rather than in smokers and in patients harboring T1
      rather than Ta tumors (p = 0.03). CONCLUSIONS: Employment in industry at risk and
      cigarette smoking resulted in being related to tumor multiplicity. The length of
      exposure to cigarette smoking was related to the natural history of the tumor. A
      drinkable water source emerged as a risk factor in absence of cigarette smoking.

PMID- 16888423
TI  - Epidemiological aspects of recruitment of male volunteers for non-invasive
      urodynamics.
AB  - INTRODUCTION: We studied epidemiological aspects of recruitment of volunteers for
      a non-invasive urodynamic study. MATERIALS AND METHODS: 9,236 volunteers were
      invited by 20 general practitioners (GPs), using two different recruitment
      methods, i.e. by mail only, or during a subsequent visit to the GP's office.
      Factors influencing the response rates were analyzed. We also tested how much the
      recruited population of volunteers differed from the general population, by
      comparing it to another, proven representative study carried out earlier in 1,662
      subjects. RESULTS: In the recruited population the prostate volumes were not
      significantly different from the proven representative study, but the symptom
      score was statistically significantly higher, although the difference was so
      small it may be called clinically irrelevant. Recruitment of volunteers in two
      steps, i.e. asking them first to visit the GP's office, and inviting them there
      to visit the outpatient clinic, rather than directly inviting them (in writing)
      to the clinic seemed to lead to a higher response, although this effect could not
      be statistically discriminated from the difference in response rates between GPs.
      CONCLUSION: The population recruited was not urologically different from the
      general population. The response depended on age, being highest around the age of
      60, and increased with social economic status. It also depended on the GP who
      recruited the subjects, and/or on the recruitment method.

PMID- 16888424
TI  - Comparison of transperitoneal versus retroperitoneal approach in laparoscopic
      radical nephrectomy for renal cell carcinoma: a single-center experience of 63
      cases.
AB  - BACKGROUND: We report our experience with the retroperitoneal (RP) and
      transperitoneal (TP) approaches for laparoscopic nephrectomy for clinically
      localized renal cell carcinoma. METHODS: Sixty-three patients with renal cell
      carcinoma were treated with laparoscopic nephrectomy, 34 by TP and 29 by RP
      approach between June 1999 and June 2003. Average age, ASA score, tumor stage and
      tumor size were similar in both groups. Early complications within 30 days and
      surgical time were retrospectively reviewed. RESULTS: Surgical time was with a
      mean of 183 and 190 minutes equal for the TP and RP approach. Intraoperative
      complications occurred in 4 patients and were vascular, requiring blood
      transfusion in 2 patients each per group. Postoperative complications were
      thromboembolism in 1 patient and subcutaneous seroma in 1 patient, both in the TP
      group. CONCLUSIONS: Although the sample size is small, it appears that the tumor
      control and surgical time in laparoscopic nephrectomy are not significantly
      influenced by the approach.

PMID- 16888425
TI  - Effects of sildenafil citrate (Viagra) on renal arteries: an evaluation with
      Doppler ultrasound.
AB  - INTRODUCTION: We aimed to determine hemodynamic alterations in renal arteries
      that may have resulted from oral intake of sildenafil citrate in healthy
      volunteers. MATERIALS AND METHODS: Twelve healthy volunteers were included in our
      study. Renal Doppler ultrasonography (US) was performed before the drug intake to
      assess the basal values. Maximum peak systolic velocity, and resistivity and
      pulsatility indices were measured from the segmental branches of both renal
      arteries in all the examinations. After the basal measurements 50 mg of
      sildenafil or placebo were randomly given to the 12 subjects. Renal Doppler US
      examinations were carried out 1 h after sildenafil or placebo intake. On the
      following day sildenafil was administered to the subjects who had previously
      taken placebo or vice versa. Renal Doppler US was repeated after 1 h. The effect
      of sildenafil on renal vascular hemodynamics was evaluated by comparison of basal
      values with postplacebo and postsildenafil values. RESULTS: No statistically
      significant differences were found between the basal values of bilateral renal
      arteries and maximum peak systolic velocity, and resistivity and pulsatility
      index values measured after the placebo or sildenafil intake. CONCLUSION: We
      demonstrated that single-dose sildenafil did not cause any significant effect on
      renal artery hemodynamics in healthy individuals.

PMID- 16888426
TI  - Indications and results of surgery for incidentally found adrenal tumors.
AB  - INTRODUCTION: The accidental discovery of an adrenal mass called incidentaloma
      has become an increasingly frequent clinical problem with the question of a
      correct and appropriate therapeutic approach being the subject of controversial
      discussions. MATERIALS AND METHODS: Clinical charts of 52 patients (22 male, 30
      female) who underwent adrenalectomy for an incidentaloma at our institution
      between 1987 and 2001 were reviewed. RESULTS: Median age was 56.4 years. Reasons
      for surgery were unclear significance in 22 patients, suspicion of malignancy in
      5, increase in size in 8, maximum tumor diameter of more than 5 cm in 7, fear of
      malignancy in 1, and subclinical secretion of cortisol in 5 patients. No data
      were available for 4 patients. Surgical resection was performed using a
      conventional transabdominal approach in 28 patients, a conventional dorsal
      approach in 17 patients, and an endoscopic retroperitoneal approach in 7
      patients. Histopathologic examination ruled out adrenal adenoma in 32 patients,
      adrenal myelolipoma in 12, unilateral nodular hyperplasia in 4, cystic lesion in
      3, and adrenocortical carcinoma in 1 patient. The mean size of all lesions was
      5.5 cm. Evaluating the criteria for surgical treatment regarding age of the
      patients and size of the lesions, 25 patients (48%), including the patient with
      the adrenocortical carcinoma, were younger than 60 years and had an adrenal
      lesion exceeding 4 cm in size. During postoperative follow-up that was available
      for 39 patients, 3 developed contralateral tumors that were treated by resection
      in 1 and by close follow-up in 2. CONCLUSIONS: Size should not be the sole
      criterion; treatment should be tailored to the individual patient. Especially in
      patients younger than 60 years with an adrenal lesion exceeding 4 cm in size, an
      adrenalectomy, predominantly via an endoscopic approach, should be carried out,
      because a repeated and life-long close follow-up of an anxious patient who has
      been informed of the diagnosis will in some cases exceed the cost of a single
      endoscopic operation.

PMID- 16888427
TI  - Shock wave lithotripsy in solitary functioning kidneys: is prophylactic stenting
      necessary?
AB  - OBJECTIVE: To assess the safety of shock wave lithotripsy (SWL) without
      prophylactic stents in solitary functioning kidneys. PATIENTS AND METHODS:
      Sixteen solitary functioning kidneys with 23 renal stones with a size of <15 mm
      were treated with SWL as the primary modality. All patients were counseled about
      the possibility of obstruction, and treatment was offered to those who consented.
      The safety of SWL was assessed by the need for interventions and the
      posttreatment renal function. RESULTS: In 14 patients lithotripsy was uneventful.
      The duration of treatment ranged from 5 to 35 days. One patient with a 15-mm
      pelvic calculus presented with anuria which resolved before intervention. In 1
      patient fragmentation failed, and percutaneous nephrolithotomy was performed.
      CONCLUSIONS: In solitary functioning kidneys, SWL is safe without prophylactic
      stents in properly selected and closely monitored patients. Avoiding stents
      decreases costs, duration of treatment, and stent-related morbidity without
      unduly compromising safety.

PMID- 16888428
TI  - Spontaneous priapism after radical retropubic prostatectomy.
AB  - We present the first case of priapism following radical prostatectomy. A 66-year
      old man with normal erections underwent radical retropubic prostatectomy with
      unilateral nerve sparing. Pathology showed a pT2c pN0 Gleason score 3 + 3 = 6
      prostate cancer and the postoperative course was uneventful. Ten days after
      surgery he recognized a spontaneous painful penile erection without sexual
      stimulation which occurred in a standing position and disappeared in a supine
      position. These episodes recurred several times during the next 3 weeks and then
      completely vanished. Pathophysiologically, we postulate intermittent position
      depending venous obstruction due to local hematoma or thrombosis.

PMID- 16888429
TI  - Renal medullary carcinoma. Case report and review of the literature.
AB  - Young patients with sickle cell trait or disease present a higher risk for renal
      medullary carcinoma, an aggressive renal tumor, with dismal prognosis, with a
      median survival of 4 months from the time of diagnosis. We report a 26-year-old
      patient with a 2-month history of bone pain at the right iliac crest, loss of
      weight, recurrent macroscopic hematuria and abdominal mass. Imaging studies
      demonstrated a 10-cm mass in the right kidney. Pathological evaluation revealed a
      medullary carcinoma and the patient died after 4 months, despite adjuvant
      treatment. Whenever a patient with sickle cell trait or disease presents with
      hematuria and/or flank pain, the possibility of a renal medullary carcinoma
      should always be kept in mind, with thorough investigation and expeditious
      treatment.

PMID- 16888430
TI  - Adenomatous polyp of the verumontanum accompanied by parabulbous epidermoid cyst
      and cryptorchidism in an adult male.
AB  - The coexistence of polyp of the verumontanum, epidermoid paraurethral cyst and
      cryptorchidism presents a mosaic of congenital anomalies of the urogenital tract.
      We present a 30-year-old patient with a medical history of unilateral
      cryptorchidism, urinary tract infections, obstructive voiding symptoms and
      perineal discomfort. Clinical and laboratory evaluation revealed a pending
      filling defect in the prostatic urethra and a palpable elastic mass located on
      the right side of the bulbar urethra. Transurethral resection of the urethral
      polyp with a simultaneous excision of the cystic formation via a perineal
      approach followed by a left-sided funiculolysis and orchiopexy were performed.
      Discussion focuses on the etiology and differential diagnosis of this unusual
      complex entity.

PMID- 16888431
TI  - Treatment of radiation-induced hemorrhagic cystitis with laparoscopic
      cystoprostatectomy.
AB  - Hemorrhagic cystitis can occur 6 months to 10 years after pelvic irradiation.
      Various palliative treatment alternatives may be unsuccessful in the management
      of severe hemorrhagic cystitis, so that in rare cases radical surgery will be the
      last resort.A 77-year-old man with persistent bleeding due to hemorrhagic
      cystitis after radiotherapy for prostate cancer was initially treated with
      conservative measures. All of these treatment methods were unsuccessful. His
      condition deteriorated and became life-threatening. As a last resort,
      laparoscopic cystoprostatectomy and mini-laparotomy ileal conduit diversion were
      successfully performed with no intraoperative or postoperative complications. To
      our knowledge, this is the first report on laparoscopic cystoprostatectomy for a
      patient with previous radiotherapy to the pelvis.

PMID- 16888433
TI  - Gene therapy for hemophilia.
AB  - PURPOSE OF REVIEW: This review will highlight the progress achieved in the past 2
      years on using gene therapy to treat hemophilia in animals and humans. RECENT
      FINDINGS: There has been substantial progress in using gene therapy to treat
      animals with hemophilia. Novel approaches for hemophilia A in mice include
      expression of Factor VIII in blood cells or platelets derived from ex-vivo
      transduced hematopoietic stem cells, or in-vivo transfer of transposons
      expressing Factor VIII into endothelial cells or hepatocytes. Advances in large
      animal models include the demonstration that neonatal administration of a
      retroviral vector expressing canine Factor VIII completely corrected hemophilia A
      in dogs, and that double-stranded adeno-associated virus vectors resulted in
      expression of Factor IX that is 28-fold that obtained using single-stranded adeno
      associated virus vectors. In humans, one hemophilia B patient achieved 10% of
      normal activity after liver-directed gene therapy with a single-stranded adeno
      associated virus vector expressing human Factor IX. Expression fell at 1 month,
      however, which was likely due to an immune response to the modified cells.
      SUMMARY: Gene therapy has been successful in a patient with hemophilia B, but
      expression was unstable due to an immune response. Abrogating immune responses is
      the next major hurdle for achieving long-lasting gene therapy.

PMID- 16888434
TI  - Continuous infusion of coagulation factors: current opinion.
AB  - PURPOSE OF REVIEW: To review the most recent reports on continuous infusion of
      coagulation factors, focusing on the current issues relating to this mode of
      therapy. RECENT FINDINGS: Continuous infusion has been extensively used as an
      alternative to intermittent bolus factor replacement since the 1990s. To date,
      more than 100 reports comprising more than 800 continuous infusion treatments in
      various clinical situations have been published, with an increase in the current
      utilization of recombinant coagulation factors. An excellent hemostatic efficacy
      of continuous infusion has been reported. Continuous infusion protocols, however,
      still vary widely in terms of the different hemostatic levels targeted, dosage
      regimens, modes of continuous infusion and duration of therapy, which obviously
      result in variations in the cost-effectiveness reported by different centers.
      SUMMARY: Continuous infusion has been shown to be a safe and cost-effective mode
      of replacement for treatment of hemophilia. The lack of evidence-based
      information on the hemostatic levels to be maintained in specific clinical
      situations, and recent concerns regarding the development of inhibitors,
      particularly in patients with mild hemophilia treated with continuous infusion,
      need to be addressed by prospective, randomized studies that compare traditional
      intermittent injections and the continuous infusion mode of factor replacement.

PMID- 16888435
TI  - Risk of inhibitors in haemophilia and the type of factor replacement.
AB  - PURPOSE OF REVIEW: Inhibitors in haemophilia are a serious complication that may
      render usual replacement therapy ineffective. The risk is greatest in previously
      untreated children with severe haemophilia A. The role of replacement factor VIII
      in this group is an important issue. RECENT FINDINGS: Until now, few clinical
      studies have correctly taken into account the variety of cofactors involved in
      inhibitor development: genetic (familial antecedents, ethnicity, F8 and immune
      response genotypes), and environmental cofactors (age at first infusion,
      prophylaxis and intensity of treatment). This is a prerequisite to correctly
      evaluating the putative role of the type of factor replacement. Prospective
      cohort studies are therefore urgently needed. Depending on the expected inhibitor
      risk in the reference group, the intensity of the relationship between risk
      factor and endpoint, the duration of patient follow up, and the design of the
      study (balanced or unbalanced groups), cohorts including 200-500 previously
      untreated children should be sufficient to demonstrate an increased intensity of
      risk of about 2 or more with one product compared with another. SUMMARY: Aside
      from clinical studies, fundamental research is essential to test the multiple
      hypotheses that could explain a difference in inhibitor risk between the
      currently available factor VIII concentrates in order to develop less immunogenic
      factor VIII.

PMID- 16888436
TI  - A critical comparison of platelet preparation methods.
AB  - PURPOSE OF REVIEW: Platelet concentrates may be prepared from whole blood or by
      plateletpheresis. Currently, the non-evidence-based preponderance of apheresis
      units in the United States and the 50: 50 ratio in Europe may not optimize the
      gifts of whole-blood donors or minimize healthcare costs. Post-storage pooled,
      whole-blood-derived platelets, on the other hand, do not provide the convenience
      of or an equivalent level of safety as apheresis platelets. RECENT FINDINGS: Some
      data suggest that different methods of manufacture of whole-blood-derived
      platelets (platelet-rich plasma or buffy coat intermediate steps) result in
      differing degrees of platelet activation, which may impact on the quality of
      stored concentrates. Recent studies have observed superior radiolabel recovery
      and post-transfusion increments for platelets derived from apheresis compared
      with platelet-rich plasma whole-blood-derived platelets. A pre-storage pooling
      system for whole-blood-derived platelets has just been licensed in the USA, and
      may eventually combine the benefits of apheresis-derived and whole-blood-derived
      platelets. The advantages of the European method of manufacture of buffy coat
      whole-blood-derived platelet concentrate have convinced the Canadian Blood
      Services to abandon platelet-rich-plasma-derived concentrates. SUMMARY: We
      present a literature-based review of the relative merits of apheresis-derived and
      whole-blood-derived platelets. Additional studies are needed in order to define
      the optimal proportion of the platelet supply from apheresis collections and the
      choice of whole-blood-derived production method for US blood providers.

PMID- 16888437
TI  - Aspirin resistance: is this term meaningful?
AB  - PURPOSE OF REVIEW: To review data for and against the existence of 'aspirin
      resistance', a term coined to indicate aspirin-treated patients having ex-vivo
      tests of platelet activation insensitive to aspirin treatment and recurrence of
      cardiovascular disease. RECENT FINDINGS: 'Aspirin resistance' defined by ex-vivo
      tests of platelet activation yielded values ranging from 21 to 78%, indicating
      that such tests do not provide a useful measurement. In long-term aspirin-treated
      patients, studies demonstrated small but functionally relevant platelet
      thromboxane A2 formation that was responsible for an enhanced platelet activation
      in response to platelet agonist. These studies, however, did not fully exclude
      that aspirin compliance may be implicated in such phenomena. Two trials performed
      in patients with coronary artery disease demonstrated that laboratory evidence of
      aspirin resistance was no longer detectable when aspirin compliance was
      accurately monitored. SUMMARY: Given the multifactorial nature of
      atherothrombosis, recurrence of cardiovascular events in aspirin-treated patients
      does not necessarily suggest 'drug failure'. A cause-effect relationship between
      platelet insensitivity to aspirin and cardiovascular recurrence has not been
      defined overall because aspirin compliance has been scarcely considered. Until
      this information is taken into account, the existence of 'clinical resistance' to
      aspirin should be reconsidered.

PMID- 16888438
TI  - Who should be tested for thrombophilia?
AB  - PURPOSE OF REVIEW: The purpose of this review is to identify on the basis of
      available data and expert opinions who would benefit most from screening for
      thrombophilia. RECENT FINDINGS: Recent studies have clearly defined the risk of
      venous thromboembolism in members of families with inherited thrombophilia. Meta
      analyses have shown the role of the most common thrombophilic conditions in
      increasing the risk of recurrent venous thromboembolism in carriers. Screening
      for thrombophilia in venous thromboembolism patients might help identify those at
      higher risk of recurrences even though it is unclear how this information can be
      of use in modifying their management. Thrombophilia seems to play a role in early
      fetal losses as also shown in women at their first intended pregnancy, which
      makes it interesting to screen women after only one bad pregnancy outcome.
      SUMMARY: Screening for thrombophilia can be performed particularly in young
      patients with venous thromboembolism. Carriers of inherited thrombophilia are at
      increased risk of venous thromboembolism recurrences. Screening families of
      venous thromboembolism patients with thrombophilia allows the identification of
      still asymptomatic carriers who may benefit from thromboprophylaxis. This may be
      true of women in fertile age belonging to thrombophilic families. In
      thrombophilic women with pregnancy complications prophylaxis may be offered to
      prevent recurrences.

PMID- 16888439
TI  - Diagnosis of pulmonary embolism: in transition.
AB  - PURPOSE OF REVIEW: To discuss reports published in 2005 on the diagnosis of
      clinically suspected nonmassive pulmonary embolism. RECENT FINDINGS: Progress has
      been made in assessing the clinical probability of pulmonary embolism, in
      addressing diagnosis in the elderly, in evaluating the diagnostic performance of
      single-detector and multidetector row helical computed tomography, and in the
      role of D-dimer measurement and lower limb venous compression ultrasonography in
      the diagnostic work-up of pulmonary embolism. SUMMARY: Diagnosing venous
      thromboembolism depends mainly on noninvasive diagnostic tools that are used
      sequentially. In most patients, a noninvasive work-up is feasible and the
      diagnostic algorithms are becoming simpler. This review focuses on developments
      in clinical probability assessment, pulmonary embolism in the elderly, potential
      new uses of D-dimer measurement, advent of multidetector row helical computed
      tomography, and utility of ultrasonography in detecting deep vein thrombosis in
      patients with suspected pulmonary embolism. With the development of potentially
      more sensitive diagnostic tests for pulmonary embolism, physicians are now facing
      the risk of overdiagnosis and hence overtreatment. The issue will no longer be
      just to detect clots but to identify patients who must be treated using
      anticoagulants, a complicated question.

PMID- 16888440
TI  - Retrievable vena cava filters: a review.
AB  - PURPOSE OF REVIEW: To examine the current literature regarding retrievable
      inferior vena cava filters and to discuss the appropriate indications for their
      clinical use. RECENT FINDINGS: Permanent filters have been shown to be effective,
      but have a number of long-term complications such as filter thrombosis or
      migration. Indications for their placement should be accurately evaluated,
      especially in patients with a long life expectancy, or in whom the period of
      contraindication to anticoagulation is short. On the other hand, temporary
      filters are difficult to manage and their maximum implantation time is often
      insufficient to solve the clinical problem leading to their placement. Four
      different retrievable filters recently received approval for temporary insertion.
      Recent data suggest that the use of these filters may be related to a low rate of
      pulmonary embolism and insertion complications. Nevertheless, no randomized
      clinical trials have been performed, and the only available data refer to
      retrospective or prospective studies. SUMMARY: Retrievable filters are a new
      generation of filter that offers the attractive possibility of being left in
      place permanently or being removed after quite a long period when they become
      unnecessary.

PMID- 16888441
TI  - Genetic influences on the response to warfarin.
AB  - PURPOSE OF REVIEW: Warfarin has a narrow therapeutic index and there is wide
      interindividual variability in the drug dose requirement. Uncertainty of response
      renders currently used loading regimens inaccurate as they fail to take into
      account individual patient factors that have a major influence on anticoagulation
      response. This review focuses on recent research findings demonstrating the
      impact of genetics on warfarin sensitivity and dose requirement and the issues
      concerning the clinical utility of individualized therapy. RECENT FINDINGS:
      Single-nucleotide polymorphisms in cytochrome P450 2C9 and vitamin K epoxide
      reductase have been shown to make significant contributions to the variability in
      warfarin dose requirements. Polymorphisms in other genes that mediate the actions
      of warfarin make little or no contribution to the variability. Racial and
      cultural differences influence dose requirements, which can be explained at least
      in part by genetic and dietary factors. SUMMARY: Individualization of therapy
      based on genetic and environmental factors has the potential to reduce the
      adverse effects associated with the commencement of warfarin therapy. Prospective
      studies that incorporate both CYP2C9 and VKORC1 genes and environmental factors
      in warfarin dose calculation will be required to demonstrate the safety, cost
      effectiveness, and feasibility of individualized dosing regimens.

PMID- 16888442
TI  - Thrombosis as a harbinger of cancer.
AB  - PURPOSE OF REVIEW: The aim of this review is to explore the state of the art
      knowledge on the possible association between venous thromboembolism, especially
      idiopathic venous thromboembolism, and occult cancer, and to speculate on its
      implications. RECENT FINDINGS: Venous thromboembolism, especially idiopathic
      venous thromboembolism, is sometimes associated with a subsequent increased risk
      of newly discovered cancers during the follow-up period. Its incidence
      approximates 10%. The performance of extensive screening procedures for cancer
      identification when venous thromboembolism is diagnosed appears advisable if it
      provides an impact on cancer-related mortality. Recent prospective trials have
      observed that, thanks to extensive screening procedures, most hidden cancers are
      detected at baseline or at an earlier stage. Data from these studies do not
      conclusively demonstrate that earlier diagnosis ultimately prolongs life, but the
      collective observation makes such a beneficial effect likely. SUMMARY: Venous
      thromboembolism, especially in its idiopathic presentation, may sometimes be a
      marker for a hidden cancer. With extensive screening procedures, the earlier
      discovery of cancer, which might mean identification of the disease at an
      attachable stage, may be crucial, because innovations in treatment protocols
      provide increasing chances of success and the eradication of cancer.

PMID- 16888443
TI  - Antiphospholipid antibodies and the antiphospholipid syndrome: an update on
      treatment and pathogenic mechanisms.
AB  - PURPOSE OF REVIEW: The antiphospholipid syndrome is a disorder of recurrent
      thrombosis, pregnancy loss and thrombocytopenia associated with the presence of
      antiphospholipid antibodies and persistently positive anticardiolipin or lupus
      anticoagulant positive tests. Since its recognition in the 1980s, growing
      interest in the field, not only with respect to diagnosis and treatment, but also
      regarding the pathogenesis of antiphospholipid antibodies, has emerged. RECENT
      FINDINGS: First, this review addresses the recently updated classification
      criteria for diagnosis and treatment of the antiphospholipid syndrome. A
      discussion on the newly described potential beneficial roles of
      hydroxychloroquine and the statins for the treatment of antiphospholipid syndrome
      associated clinical manifestations is included. Importantly, this article
      analyzes recent data that examine the molecular and intracellular events that
      antiphospholipid antibodies trigger in target cells, as well as new findings in
      the identification of the receptors for these antibodies on the membrane of those
      cells. A separate section discusses novel pathogenic mechanisms of
      antiphospholipid antibodies, including the activation of complement and their
      interaction with homologous catalytic domains of several serine proteases of the
      coagulation system. SUMMARY: Understanding the molecular interactions and the
      intracellular signaling that antiphospholipid antibodies trigger, new therapeutic
      and targeted strategies to ameliorate clinical manifestations in patients with
      antiphospholipid syndrome may be established.

PMID- 16888444
TI  - Prophylaxis and treatment of thrombophilia in pregnancy.
AB  - PURPOSE OF REVIEW: This review addresses the prophylaxis and treatment of
      thrombophilia in pregnancy, which is associated with increased risk of venous
      thromboembolism and placental vascular complications. RECENT FINDINGS: Topics
      include preventing deep vein thrombosis recurrence in pregnant women with
      constitutional thrombophilias, using prophylactic heparins throughout pregnancy
      and postpartum anticoagulants. Cases of thrombosis still occur in the postpartum
      period and other therapeutics should be tested. Primary prophylaxis is acceptable
      for high-risk thrombophilias. Early pregnancy losses (before the 10th week) are
      not associated with constitutional thrombophilias. The natural prognosis of
      embryonic losses associated with current thrombogenic polymorphisms is good,
      unlike fetal losses associated with the same thrombophilias: in this case, a
      prophylactic low-molecular-weight heparin given from the beginning of the 8th
      week is more efficient than low-dose aspirin. Data are lacking on the prevention
      of severe preeclampsia, placental abruption, or intrauterine growth restriction
      in women with constitutional thrombophilias; preliminary results indicate that
      low-molecular-weight heparin may have some preventive effect. Specific studies
      are needed. SUMMARY: Recent studies have shown the limits of available procedures
      for women with constitutional thrombophilia and have helped define the clinical
      situations in thrombophilia-related placental insufficiency in which prophylactic
      low-molecular-weight heparin may be indicated.

PMID- 16888445
TI  - The endothelial protein C receptor.
AB  - PURPOSE OF REVIEW: The endothelial cell protein C receptor is known to be
      critical for the regulation of natural anticoagulant functions and some anti
      inflammatory and anti-apoptotic functions of activated protein C. This leads to
      the prediction that abnormalities in endothelial cell protein C receptor might be
      associated with altered thrombotic tendencies and hyperinflammatory responses to
      infectious agents. This review covers the most recent evidence that relatively
      common genetic and acquired abnormalities of endothelial cell protein C receptor
      do contribute to pathophysiological disease processes. RECENT FINDINGS: In mice,
      increases and decreases in endothelial cell protein C receptor expression are
      shown to modulate the coagulation and inflammatory proceses. Genetic
      polymorphisms are associated with alterations in protein expression and familial
      and acquired thrombotic disease. SUMMARY: The emerging clinical evidence of
      endothelial cell protein C receptor involvement in thrombotic disease suggests
      that the understanding of endothelial cell protein C receptor genotype and the
      knowledge of auto-antibodies may aid in diagnosing the risk of thrombotic events
      in patients.

PMID- 16888446
TI  - Bibliography. Current world literature. Hemostasis and thrombosis.

PMID- 16888447
TI  - Pathophysiological characteristics of heart rate recovery in heart failure.
AB  - PURPOSE: Heart failure (HF) is associated with blunted HR recovery after
      exercise. The determinants of altered HR recovery in HF are unknown. The aim of
      this study was to investigate clinical correlates of HR recovery in HF patients.
      METHODS: Echocardiography, pulmonary function tests, exercise testing, and
      neurohormonal measurements were performed in 98 HF patients. HR recovery was
      calculated as the difference between heart rate at peak exercise and at 1 min
      into a recovery period. Study subjects were divided into three groups based on HR
      recovery tertiles: group 1 (HR recovery < or = 6 bpm), group 2 (7 < or = HR
      recovery < or = 12), and group 3 (HR recovery > or = 13). RESULTS: There were
      significant differences between the groups in multiple parameters. Compared with
      group 3, patients in group 1 had greater E/A ratios (1.81 +/- 0.26 vs 0.98 +/-
      0.12, P = 0.011), shorter deceleration time (170 +/- 11 vs 223 +/- 11 ms, P =
      0.016), and higher plasma atrial natriuretic peptide levels (207 +/- 32 vs 101 +/
      12 pg.mL, P = 0.008), indicating higher left ventricular filling pressures and
      elevated left atrial pressures. Pulmonary function tests were suggestive of
      greater restrictive changes in the lungs. Finally, subjects in group 1 had
      impaired exercise capacity, as evidenced by shorter exercise duration (5.2 +/-
      0.2 vs 8.3 +/- 0.4 min, P < 0.001), lower peak VO2 (14.6 +/- 0.6 vs 22.2 +/- 1.0
      mL.kg(-1).min(-1), P < 0.001), higher VE/VCO2 ratios (36.4 +/- 1.1 vs 31.1 +/-
      0.9, P = 0.001), and reduced chronotropic responses to exercise (39 +/- 3 vs 69
      +/- 4 bpm, P < 0.001). CONCLUSION: HR recovery may be a clinically useful index
      identifying HF patients with distinct echocardiographic, neurohormonal, and
      hemodynamic characteristics. This may have implications for our understanding of
      the pathophysiology of impaired HR recovery in HF as well as for the clinical
      evaluation of such patients.

PMID- 16888448
TI  - Noninvasive evaluation of skeletal muscle oxidative metabolism after heart
      transplant.
AB  - PURPOSE: The main aim of the present study was to investigate skeletal muscle
      oxidative metabolism in heart transplant recipients (HTR) by noninvasive tools.
      METHODS: Twenty male HTR (age 50.4 +/- 2.6 yr; mean +/- SE) and 17 healthy
      untrained age-matched controls (CTRL) performed an incremental exercise (IE) and
      a series of constant-load (CLE) moderate-intensity exercise tests on a
      cycloergometer. The following variables were determined: heart rate (HR); breath
      by-breath pulmonary O2 uptake (VO2); and skeletal muscle (vastus lateralis)
      oxygenation indices by continuous-wave near-infrared spectroscopy. Changes in
      concentration of deoxygenated hemoglobin (Hb) and myoglobin (Mb) (Delta[deoxy(Hb
      + Mb)]), expressed as a fraction of values obtained during a transient limb
      ischemia, were taken as an index of skeletal muscle O2 extraction. "Peak" values
      were determined at exhaustion during IE. Kinetics of adjustment of variables were
      determined during CLE. RESULTS: VO2peak, HRpeak, and Delta[deoxy(Hb + Mb)] peak
      were significantly lower in HTR than in CTRL (17.1 +/- 0.7 vs 34.0 +/- 1.9 mL.kg(
      1).min(-1), 133.8 +/- 3.8 vs 173.0 +/- 4.8 bpm, and 0.42 +/- 0.03 vs 0.58 +/-
      0.04, respectively). In HTR, Delta[deoxy(Hb + Mb)] increase at submaximal
      workloads was steeper than in CTRL, suggesting an impaired O2 delivery to
      skeletal muscles, whereas the lower Delta[deoxy(Hb + Mb)] peak values suggest an
      impaired capacity of O2 extraction at peak exercise. VO2 and HR kinetics during
      CLE were significantly slower in HTR than in CTRL, whereas, unexpectedly, no
      significant differences were found for Delta[deoxy(Hb+Mb)] kinetics (mean
      response time: 21.3 +/- 1.1 vs 20.2 +/- 1.2 s). CONCLUSION: The findings confirm
      the presence of both "central" (cardiovascular) and "peripheral" (at the skeletal
      muscle level) impairments to oxidative metabolism in HTR. The noninvasiveness of
      the measurements will allow for serial evaluation of the patients, in the
      presence and/or absence of rehabilitation programs.

PMID- 16888450
TI  - VO2peak prediction and exercise prescription for pregnant women.
AB  - PURPOSE: The present study was designed to develop and validate a prediction
      equation for peak oxygen consumption VO2peak) using a progressive treadmill test
      and to refine the current target HR exercise guidelines for pregnancy (PARmed-X
      for Pregnancy). METHODS: One hundred fifty-six women between 16 and 22 wk of
      gestation performed the test to volitional fatigue (peak exercise test). Data
      from every fourth subject were used to form the cross-validation group. The women
      were separated into two age groups; 20-29 (N = 60) and 30-39 (N = 96) yr of age
      and then further separated into fit (VO2peak at the top 25th percentile), unfit
      (VO2peak at the bottom 25th percentile), and active (between these two ranges).
      HR and VO2peak values were used in the regression equation to predict target HR
      ranges at 60 and 80% VO2peak. RESULTS: The prediction equation (R2 = 0.72,
      R2adjusted = 0.71 and SEE = 2.7) was compared with cross validation (N = 39; P =
      0.78). Fit women had a VO2peak > or = 27.2 mL.kg(-1).min(-1) and > or = 26.1
      mL.kg.min for ages 20-29 and 30-39 yr, respectively, representing the top 25th
      percentile. Unfit women had a VO2peak of < or = 21.0 mL.kg(-1).min(-1) and < or =
      19.6 mL.kg(-1).min(-1), respectively, representing the bottom 25th percentile.
      HR/VO2peak regression lines for each fitness level were used to generate the
      target HR zones in each age group. CONCLUSION: This is the first study to provide
      a validated prediction equation of VO2peak for pregnant women using a progressive
      treadmill exercise test. The defined target HR zones based on age and the
      appropriate fitness levels can be used for exercise prescription in healthy
      pregnant women.

PMID- 16888449
TI  - The effect of type 2 diabetes on diastolic function.
AB  - PURPOSE: This study aimed to determine whether sedentary overweight subjects with
      type 2 diabetes have impaired diastolic function compared with equally sedentary
      and overweight nondiabetic subjects. METHODS: Mitral valve pulsed Doppler
      echocardiography and tissue Doppler imaging (TDI) were used to assess left
      ventricular structure and diastolic function in 40- to 60-yr-old sedentary
      overweight subjects with type 2 diabetes (N = 13) and age- and body mass-matched
      sedentary nondiabetic subjects (N = 15). Pseudonormal filling was identified
      using preload reduction and TDI. RESULTS: Traditional Doppler mitral inflow
      parameters were not different between groups; however, early diastolic
      relaxation, as measured by peak early mitral annular velocity (E') and the ratio
      of E' and peak late mitral annular velocity (E'/A'), was reduced in type 2
      diabetic subjects (P < 0.05). The ratio of peak early mitral inflow (E) to E'
      (E/E'), an estimate of left ventricular filling pressure, was also higher in the
      type 2 diabetes group (P < 0.05). The proportions of diastolic impairment (69 vs
      40%) and pseudonormal filling (39 vs 20%) were not different between groups (P =
      0.18). CONCLUSION: These findings suggest that type 2 diabetes has an effect on
      diastolic function that is independent of age and body composition.

PMID- 16888451
TI  - Genetic effects on physical activity: results from the Swedish Twin Registry.
AB  - PURPOSE: The aim of this study was to investigate the genetic effects on leisure
      time physical activity using data from the Swedish Twin Registry. METHODS: We
      investigated 13,362 twin pairs (5334 monozygotic and 8028 dizygotic pairs) aged
      14-46 yr. Information on leisure-time physical activity was obtained by
      questionnaire. Correlations and odds ratios of physical activity were calculated
      for males, females, and monozygotic and dizygotic twins, respectively. Structural
      equation modeling was used to estimate the contribution of genetic effects as
      well as common and nonshared environmental factors on leisure-time physical
      activity. RESULTS: About one third of the twins reported that they exercised
      regularly (26% in females and 39% in males). The correlations of physical
      activity were twice as high in monozygotic compared with dizygotic twins,
      suggesting the presence of genetic effects. The variation in physical activity
      due to heritage was 57% (95% confidence interval (CI) = 0.49-0.63) in males and
      50% (95% CI = 0.49-0.55) in females. The common environmental influence on
      physical activity was very small compared with the influence from environmental
      factors unique to the individual. CONCLUSIONS: Our study establishes heredity as
      an important component behind individual differences in physical activity in
      adult men and women. This may be one reason behind difficulties in convincing
      people to adopt an active lifestyle. Still, this study shows that there is a
      substantial influence on physical activity from environmental factors unique to
      the individual.

PMID- 16888452
TI  - Pedometer-determined physical activity and body composition in New Zealand
      children.
AB  - PURPOSE: The objectives of this study were to examine current levels of pedometer
      determined physical activity in a multiethnic sample of New Zealand children and
      to investigate associations among weekday and weekend step counts, body mass
      index (BMI), waist circumference (WC), and percentage body fat (%BF). METHODS: A
      total of 1115 children (536 boys, 579 girls) aged 5-12 yr wore sealed multiday
      memory pedometers for three weekdays and two weekend days. The ethnic composition
      of the sample was 49.2% European, 30.0% Polynesian, and 16.5% Asian, with 4.3%
      from other ethnicities. BMI was determined from height and weight, and %BF was
      measured using hand-to-foot bioelectrical impedance analysis. Participants were
      classified as normal weight, overweight, or obese using international BMI cutoff
      points (4), and into normal or central fat distribution groups using national WC
      standards (28). The 90th percentile of %BF for each age and sex subgroup was used
      to identify normal and high body fatness. RESULTS: Mean step counts for this
      sample were 16,133 +/- 3,864 (boys) and 14,124 +/- 3,286 (girls) on weekdays, and
      12,702 +/- 5,048 (boys) and 11,158 +/- 4,309 (girls) on weekends. Significant
      differences in step counts were observed between weekdays and weekends, boys and
      girls, and among age, ethnic, and socioeconomic groups. Analysis of variance
      revealed stronger associations between step counts and %BF category than between
      step counts and BMI or WC groups. CONCLUSION: This study provides evidence of a
      link between daily step counts and body fatness in children. Our results also
      suggest that the promotion of physical activity during the weekend is a key
      priority for young New Zealanders.

PMID- 16888453
TI  - Leukocyte's Hif-1 expression and training-induced erythropoietic response in
      swimmers.
AB  - PURPOSE: Altitude training is popular among athletes to augment oxygen delivery
      capabilities to tissues and to improve physical performance. Hypoxia inducible
      factor-1 (HIF-1) controls the expression of several genes' encoding involved in
      physiological responses towards reduced oxygen availability, in particular by
      increasing serum erythropoietin (EPO). It may be involved in the individual
      variability for erythropoietic markers and/or sea-level performance of athletes
      using altitude during their training. Therefore, we investigated whether, before
      training, evolutions of hif-1alpha and ahif (HIF-1alpha natural antisense)
      transcript amounts and HIF-1alpha protein quantities in leukocytes measured
      during an acute hypoxia normobaric test (3 h at 3000 m at rest) could allow to
      predict poor and good responders for hematological markers after a "living high
      training low" protocol. METHODS: Eighteen elite swimmers were divided into two
      groups that followed a 13-d training program: "living low-training low" (1200 m)
      (LL) or "living high (2500-3000 m)-training low (1200 m)" (LH). RESULTS: During
      the initial hypoxia test, a strong interindividual variability in the amounts of
      HIF-1alpha mRNA, aHIF transcript, and HIF-1alpha protein was observed in athlete
      leukocytes (after vs before): -82%/+396%, -100%/+229%, and -100%/+633%,
      respectively. After the test, serum erythropoietin concentration was increased
      (11.2 +/- 0.8 vs 9.8 +/- 0.8 IU.L(-1); +18%, P = 0.01). After the training
      protocol, total red cell volume (+7.6%, P = 0.04) and circulating hemoglobin
      amount (48.8 +/- 2.8 vs 45.5 +/- 3.0 mmol; i.e., +7.9%, P = 0.02) were
      significantly augmented in LH. CONCLUSION: We conclude that hif-1alpha gene
      expression quantification in leukocytes after a 3-h hypoxia test performed before
      training does not predict poor and good responder athletes to "living high
      training low" model.

PMID- 16888454
TI  - Voluntary muscle function after creatine supplementation in acute hypobaric
      hypoxia.
AB  - PURPOSE: To determine whether creatine (Cr) supplementation improves muscle
      performance during exposure to acute hypobaric hypoxia. METHODS: Seven healthy
      men (28 +/- 6 yr, mean +/- SD) performed submaximal intermittent static knee
      contractions interspersed with maximal voluntary contractions (MVCs) every minute
      to exhaustion (approximately 50% of rested MVC force) in normoxia and hypobaric
      hypoxia (separated by 3 d) after supplementation with Cr (20 g.d(-1) for 7 d then
      5 g.d(-1) for 4-7 d) or placebo (Pla) in a double-blind, randomized crossover
      study. A 5-wk period without supplementation separated treatments. Each test day,
      subjects performed two bouts (separated by 2 min) at their preset submaximal
      force, 32 +/- 4% rested MVC). RESULTS: Rested MVC force (860 +/- 66 N) and MVC
      force at exhaustion (396 +/- 27 N; 47 +/- 3% rested MVC) did not differ among
      treatments or environments (P > 0.05). For bout 1, endurance time was shorter in
      hypobaria (26 +/- 3 min) than normoxia (34 +/- 2 min) (P < 0.01), but did not
      differ between Cr (27 +/- 3 min) and Pla (33 +/- 3 min) (P > 0.05). MVC force
      returned to similar levels (P >0.05) in bout 2 after recovery in all four
      sessions (to approximately 615 N). For bout 2, endurance time also was shorter in
      hypobaria (7 +/- 1 min) than normoxia (9 +/- 1 min) (P < 0.03) but did not differ
      between Cr and Pla (P > 0.05). CONCLUSION: This study, which used an exercise
      model designed to impose the same target contraction force under all experimental
      conditions, found no effect of Cr on maximal force, muscle endurance, or recovery
      in normoxia or hypobaric hypoxia.

PMID- 16888455
TI  - Changes in ventilatory threshold at high altitude: effect of antioxidants.
AB  - PURPOSE: To investigate the effects of prolonged hypoxia and antioxidant
      supplementation on ventilatory threshold (VT) during high-altitude (HA) exposure
      (4300 m). METHODS: Sixteen physically fit males (25 +/- 5 yr; 77.8 +/- 8.5 kg)
      performed an incremental test to maximal exertion on a cycle ergometer at sea
      level (SL). Subjects were then matched on VO2peak, ventilatory chemosensitivity,
      and body mass and assigned to either a placebo (PL) or antioxidant (AO)
      supplement group in a randomized, double-blind manner. PL or AO (12 mg of beta
      carotene, 180 mg of alpha-tocopherol acetate, 500 mg of ascorbic acid, 100 mug of
      selenium, and 30 mg of zinc daily) were taken 21 d prior to and for 14 d at HA.
      During HA, subjects participated in an exercise program designed to achieve an
      energy deficit of approximately 1400 kcal.d(-1). VT was reassessed on the second
      and ninth days at HA (HA2, HA9). RESULTS: Peak power output (Wpeak) and VO2peak
      decreased (28%) in both groups upon acute altitude exposure (HA2) and were
      unchanged with acclimatization and exercise (HA9). Power output at VT (WVT)
      decreased from SL to HA2 by 41% in PL, but only 32% in AO (P < 0.05). WVT
      increased in PL only during acclimatization (P < 0.05) and matched AO at HA9.
      Similar results were found when VT was expressed in terms of % Wpeak and %
      VO2peak. CONCLUSIONS: VT decreases upon acute HA exposure but improves with
      acclimatization. Prior AO supplementation improves VT upon acute, but not chronic
      altitude exposure.

PMID- 16888456
TI  - Exogenous nitric oxide and bubble formation in divers.
AB  - PURPOSE: Prevention of bubble formation is a central goal in standard
      decompression procedures. Previously we have shown that exercise 20-24 h prior to
      a dive reduces bubble formation and increases survival in rats exposed to a
      simulated dive. Furthermore, we have demonstrated that nitric oxide (NO) may be
      involved in this protection; blocking the production of NO increases bubble
      formation while giving rats a long-lasting NO donor 20 h and immediately prior to
      a dive reduces bubble formation. This study determined whether a short-lasting NO
      donor, nitroglycerine, reduced bubble formation after standard dives and
      decompression in man. METHODS: A total of 16 experienced divers were randomly
      assigned into two groups. One group performed two dives to 30 m of seawater (msw)
      for 30 min breathing air, and performed exercise at an intensity corresponding to
      30% of maximal oxygen uptake during the bottom time. The second group performed
      two simulated dives to 18 msw for 80 min breathing air in a hyperbaric chamber,
      and remained sedentary during the bottom period. The first dive for each diver
      served as the control dive, whereas the divers received 0.4 mg of nitroglycerine
      by oral spray 30 min before the second dive. Following the dive, gas bubbles in
      the pulmonary artery were recorded using ultrasound. RESULTS: The open-water dive
      resulted in significantly more gas bubbles than the dry dive (0.87 +/- 1.3 vs
      0.12 +/- 0.23 bubbles per square centimeter). Nitroglycerine reduced bubble
      formation significantly in both dives from 0.87 +/- 1.3 to 0.32 +/- 0.7 in the in
      water dive and from 0.12 +/- 0.23 to 0.03 +/- 0.03 bubbles per square centimeter
      in the chamber dive. CONCLUSION: The present study demonstrates that intake of a
      short-lasting NO donor reduces bubble formation following decompression after
      different dives.

PMID- 16888457
TI  - Oxidative stress response in trained men following repeated squats or sprints.
AB  - PURPOSE: The purpose of this investigation was to measure the oxidative stress
      response to similarly matched work bouts of squat and sprint exercise. METHODS:
      Twelve anaerobically trained men performed six 10-s sprints and, on a separate
      occasion, repeated barbell squats to approximately equal the amount of work
      performed during the sprints. Blood lactate, heart rate, and perceived exertion
      was measured before and following each exercise bout. Muscle soreness, muscle
      force, and creatine kinase activity was determined preexercise and through 48 h
      of recovery. Desmin cytoskeletal protein was determined via muscle biopsy of the
      vastus lateralis before and at 24 h following each exercise. Plasma protein
      carbonyls (PC) and malondialdehyde (MDA) were measured as biomarkers of oxidative
      stress. RESULTS: Heart rate and perceived exertion was not different between
      exercise sessions (P > 0.05), although lactate was higher following sprinting
      compared with squatting (P = 0.002). Muscle soreness was greater for squatting
      than sprinting (P = 0.003) and reached a peak immediately postexercise for both
      sessions (P = 0.0003). Muscle force was unaffected by either exercise session (P
      > 0.05), and creatine kinase activity was elevated to a similar extent following
      both sessions. Desmin-negative fibers were virtually nonexistent after either
      exercise bout, indicating no loss of this cytoskeletal protein. Neither PC nor
      MDA was affected by the exercise (P > 0.05). CONCLUSION: These results suggest
      that in anaerobically trained men, the oxidative stress and muscle injury
      response to similarly matched anaerobic exercise bouts is minimal, and not
      different between exercise modes. Furthermore, when compared with previous
      literature on untrained subjects, the response is significantly attenuated,
      possibly because of adaptations occurring as a result of chronic, strenuous
      anaerobic training.

PMID- 16888458
TI  - Exercise-induced oxidative stress in G6PD-deficient individuals.
AB  - PURPOSE: This study was designed to investigate whether individuals with glucose
      6-phosphate dehydrogenase (G6PD) deficiency can exercise without greater
      perturbations in their redox status compared with non-G6PD-deficient individuals.
      METHODS: Nine males with established G6PD deficiency and nine males with normal
      G6PD activity performed two exhaustive treadmill exercise protocols of different
      duration (the shorter one lasting 12 min and the longer one 50 min). Several
      hematological parameters, reduced glutathione (GSH), oxidized glutathione (GSSG),
      thiobarbituric acid reactive substances (TBARS), protein carbonyls, catalase, and
      total antioxidant capacity (TAC) were measured in the blood before and after each
      exercise bout. RESULTS: Both GSH and GSSG were significantly higher in the
      control group compared with the G6PD-deficient group at baseline (0.404 +/- 0.101
      vs 0.195 +/- 0.049 mmol.L(-1) for GSH and 0.047 +/- 0.012 vs 0.012 +/- 0.006
      mmol.L(-1) for GSSG; P < 0.05); as a result, their ratio was not significantly
      different between the two groups (P > 0.05). All other oxidative stress indices
      were not different between groups at rest (P > 0.05). Exercise of both durations
      affected significantly (P < 0.05) and similarly the levels of all oxidative
      stress indices either in the G6PD-deficient group or in the control group. Only
      the long exercise affected GSH status significantly (P < 0.05), whereas both
      short and long exercise increased the levels of TBARS, protein carbonyls,
      catalase activity, and TAC to a similar extent (P < 0.05). CONCLUSION: G6PD
      deficient individuals are able to exercise until exhaustion without higher
      oxidative stress compared with non-G6PD-deficient individuals. Exercise duration
      is an important determinant of the magnitude of exercise-induced changes for GSH,
      GSSG, and GSH/GSSG, but not for TBARS, protein carbonyls, catalase activity, or
      TAC.

PMID- 16888459
TI  - Testosterone prohormone supplements.
AB  - Testosterone prohormones such as androstenedione, androstenediol, and
      dehydroepiandrosterone (DHEA) have been heavily marketed as testosterone
      enhancing and muscle-building nutritional supplements for the past decade.
      Concerns over the safety of prohormone supplement use prompted the United States
      Food and Drug Administration to call for a ban on androstenedione sales, and
      Congress passed the Anabolic Steroid Control Act of 2004, which classifies
      androstenedione and 17 other steroids as controlled substances. As of January
      2005, these substances cannot be sold without prescription. Here, we summarize
      the current scientific knowledge regarding the efficacy and safety of prohormone
      supplementation in humans. We focus primarily on androstenedione, but we also
      discuss DHEA, androstenediol, 19-nor androstenedione, and 19-nor androstenediol
      supplements. Contrary to marketing claims, research to date indicates that the
      use of prohormone nutritional supplements (DHEA, androstenedione, androstenediol,
      and other steroid hormone supplements) does not produce either anabolic or
      ergogenic effects in men. Moreover, the use of prohormone nutritional supplements
      may raise the risk for negative health consequences.

PMID- 16888460
TI  - Effects of body position on slide boarding performance by cross-country skiers.
AB  - PURPOSE: In this study, we examined the effects of body position (from deep to
      high position) in slide boarding by well-trained cross-country skiers. The main
      hypothesis was that a deeper, more "crouched" position would lead to reduced air
      resistance and enhanced power production during explosive extension of the lower
      limbs, and thereby to an increased performance, even though the upper extremity
      may not be used for poling in this deep position. METHODS: Measurements (air
      resistance in a wind tunnel, power output, kinematics, gas exchange, and blood
      lactate levels) were performed during a 30-s maximal test and a 3-min maximal
      test performing (imitation) ski-skating movements on a sliding board at three
      different body positions (high, moderate, and deep). RESULTS: Our findings
      indicate that a deep position enhances power production by 24% and reduces air
      resistance by 30% for the 30-s maximal test. Power production did not increase in
      the 3-min test, but lactate levels after exercise were increased in the deep
      position. Calculated efficiency was not affected by body position. CONCLUSION:
      The current results indicate that for a short duration, the deeper sit provides
      sufficient advantages that it may prove useful to apply such a position in sprint
      ski-skating, even though the use of the upper extremities in poling will be
      strongly hampered.

PMID- 16888461
TI  - Determining the extent of neural activation during maximal effort.
AB  - PURPOSE: The purpose of this study was to compare the extent of neural activation
      assessed by the central activation ratio (CAR) versus activation estimated from
      T2 magnetic resonance imaging (MRI) and neuromuscular electrical stimulation
      (NMES). METHODS: Seven college-age individuals volunteered for this study. CAR
      was determined by manually superimposing a train of NMES (50 Hz, 450-mus biphasic
      pulses) for 1 s during a maximal voluntary effort. The MRI-NMES method assessed
      activation by stimulating the knee extensors for 3 min in a 2 s on, 2 s off
      cycle. T2 MR images were taken at rest and after NMES was administered.
      Theoretical maximal torque (TMT) of the knee extensors was calculated based on
      the MRI-NMES activation data. The TMT was then divided by the maximal voluntary
      isometric contraction (MVIC) of each subject to determine the extent of neural
      activation during a MVIC. RESULTS: The results for CAR reveal the percent
      activation (mean +/- SD) of the quadriceps femoris during a MVIC was 92 +/- 7%
      for the right thigh and 96 +/- 4% for the left thigh. The MRI-NMES method
      estimated that MVIC could be achieved if 75 +/- 14% of the knee extensors on the
      right thigh and 74 +/- 14% on the left thigh were activated. These results are
      similar to findings that showed MVIC could be achieved by stimulating 71% of the
      knee extensors. CONCLUSIONS: We conclude that CAR overestimates the extent of
      neural activation during an MVIC because the 3D shape of the thigh is altered.
      This will change electric current flow to the axonal motor neuron branches and
      limit the artificially evoked torque, thereby resulting in an overestimation of
      CAR.

PMID- 16888462
TI  - Failure of protein to improve time trial performance when added to a sports
      drink.
AB  - INTRODUCTION: Recent studies have reported that adding approximately 2% protein
      to a carbohydrate sports drink increased cycle endurance capacity compared with
      carbohydrate alone. However, the practical implications of these studies work are
      hampered by the following limitations: (a) the rate of carbohydrate ingestion was
      less than what is considered optimal for endurance performance, and (b) the
      performance test (exercise time to fatigue) did not mimic the way in which
      athletes typically compete (i.e., a race in which a fixed distance or set amount
      of work is performed as quickly as possible). PURPOSE: We tested the hypothesis
      that adding 2% protein to a 6% carbohydrate drink (CHO-PRO) would improve 80-km
      cycling time trial performance, as compared with a 6% carbohydrate drink (CHO)
      and a nonenergetic sweetened placebo (PLAC). METHODS: Ten trained male cyclists
      (24 +/- 2 yr; VO2peak = 63 +/- 2 mL.kg(-1).min(-1); mean +/- SE) performed an 80
      km laboratory time trial (TT) on three occasions separated by 7 d. In a double
      blind crossover manner, subjects ingested CHO-PRO, CHO, or PLAC at a rate of 250
      mL every 15 min with no temporal, verbal, or physiological feedback. RESULTS:
      Time to complete the TT was 4.4% lower (P < 0.002) during CHO (135 +/- 9 min) and
      CHO-PRO (135 +/- 9) compared with PLAC (141 +/- 10), with no difference between
      CHO and CHO-PRO (P = 0.92). CONCLUSION: Ingesting 6% carbohydrate at a rate of 1
      L.h(-1) (60 g.h(-1)) improved an 80-km TT performance in trained male cyclists.
      However, adding 2% protein to a 6% carbohydrate drink provided no additional
      performance benefit during a task that closely simulated the manner in which
      athletes typically compete.

PMID- 16888463
TI  - Pacing strategy and the occurrence of fatigue in 4000-m cycling time trials.
AB  - PURPOSE: The present study was designed to examine the role of central and
      peripheral fatigue on 4000-m cycling time trial performance by comparing changes
      in power output and integrated electromyography (iEMG) in differently paced
      maximal efforts. METHODS: Eight well-trained men performed three randomly ordered
      time trials with different pacing strategies, in which the first 2000 m were
      manipulated to evoke an increasing, even, and decreasing power output profile
      (SUB, EVEN, and SUPRA, respectively). Subjects were instructed to finish the last
      2000 m of all trials in the shortest time possible. iEMG of the rectus femoris
      (RF), vastus lateralis (VL), and biceps femoris (BF) muscle, mechanical power
      output, and gas exchange variables were measured. Anaerobic and aerobic
      contributions to mechanical power output were calculated from gas exchange data.
      RESULTS: The increase in mechanical power output during the SUB time trials was
      always associated with an increase in iEMG in all muscles. A decrease in
      mechanical power output near the end of the time trials was also marked by an
      increase in iEMG for all muscles, except for the RF. Comparing the last 2000-m
      interval with the first, aerobic power output increased for all strategies.
      Anaerobic power output increased in SUB and decreased in EVEN and SUPRA.
      CONCLUSION: The relationship between iEMG and mechanical power output pattern was
      consistent with peripheral fatigue rather than central downregulation of
      mechanical power output. Specifically, anaerobic energy resources seem to be
      important in regulating pacing strategy.

PMID- 16888464
TI  - Metabolism and performance in repeated cycle sprints: active versus passive
      recovery.
AB  - PURPOSE: To compare active versus passive recovery on performance and metabolism
      during a test of repeated-sprint ability. METHODS: Nine males performed four
      repeated-sprint cycle tests (six 4-s sprints, every 25 s) in a randomized,
      counterbalanced order: two tests with active recovery (approximately 32% VO2max)
      and two with passive recovery. Muscle biopsies were taken during the four tests
      from the vastus lateralis pretest, immediately posttest, and following 21 s of
      recovery to determine phosphocreatine ([PCr]), creatine, and muscle lactate
      concentration ([MLa]). RESULTS: Active recovery resulted in a greater power
      decrement than passive recovery (7.4 +/- 2.2 vs 5.6 +/- 1.8%, P = 0.01) and lower
      final peak power (14.9 +/- 1.5 vs 15.3 +/- 1.5 W.kg(-1), P = 0.02). However,
      there was no significant difference in work decrement or total work. The percent
      of resting [PCr] was lower and approached significance posttest (32.6 +/- 10.6 vs
      45.3 +/- 18.6%; P = 0.06; effect size (ES) = 0.8) and following 21 s of recovery
      (54.6 +/- 9.6 vs 71.7 +/- 14.1%; P = 0.06; ES = 1.2) during active recovery. The
      [MLa] was significantly higher posttest during active recovery (71.7 +/- 12.3 vs
      55.2 +/- 15.7 mmol.kg(-1)dm; P = 0.048; ES = 1.2); however, no significant
      differences were evident following 21 s of recovery (55.0 +/- 11.3 vs 48.4 +/-
      16.7 mmol.kg(-1)dm, P = 0.07; ES = 0.5). CONCLUSIONS: Despite no differences in
      the majority of performance measures, active recovery resulted in a significantly
      lower final peak power, a greater peak power decrement, a higher [MLa], and a
      strong trend towards lower [PCr], suggesting a potential suboptimal effect of
      active recovery during repeated-sprint exercise.

PMID- 16888465
TI  - Influence of maxillary mouthguards on physiological parameters.
AB  - INTRODUCTION: The purpose of this study was to test the influence of two types of
      maxillary mouthguards (a self-adapted and a custom-made model: SA and CM,
      respectively) on various physiological parameters generally associated with
      performance in team sports. METHODS: Nineteen trained male subjects participating
      in team sports were tested. Visual reaction time, explosive power, ventilation at
      rest, and ventilation and oxygen consumption during submaximal and maximal
      exercise were measured in three randomized conditions: normal, with SA
      mouthguards, or with CM mouthguards. RESULTS: Wearing SA or CM mouthguards did
      not significantly alter any of the measured parameters compared with the normal
      condition. CONCLUSIONS: Wearing a maxillary mouthguard does not affect the main
      physiological parameters generally associated with team sport performance. These
      results provide additional support to the policy of encouraging athletes to wear
      individually fitted maxillary mouthguards.

PMID- 16888466
TI  - Reliability of air displacement plethysmography in a large, heterogeneous sample.
AB  - INTRODUCTION: Several studies have assessed the validity of air displacement
      plethysmography (ADP), but few have assessed the reliability of ADP using a
      large, heterogeneous sample. PURPOSE: This study was conducted to determine the
      reliability of ADP using the Bod Pod in a large, heterogeneous sample. METHODS: A
      total of 980 healthy men and women (30 +/- 15 yr, mean +/- SD) completed two body
      composition assessments separated by 15-30 min. All testing was done in
      accordance with the manufacturer's instructions. RESULTS: A significant
      correlation (r = 0.992, P = 0.001) was found between body density (BD) 1 (1.046
      +/- 0.001 kg.L(-1); mean +/- SEM) and BD 2 (1.046 +/- 0.001 kg.L(-1). A paired t
      test revealed no significant difference between BD 1 and 2 (P = 0.935). The
      coefficient of variation (CV) for BD was 0.15%. A significant intraclass
      correlation coefficient (ICC) was found for BD (ICC = 0.996, P = 0.001), and the
      standard error of measurement (SEM) was 0.001 kg.L(-1). Body mass (BM) 1 and 2
      were correlated significantly (r = 0.999, P = 0.001); however, a significant (P =
      0.001) decrease was seen from BM 1 (75.510 +/- 0.461 kg) to BM 2 (75.497 +/-
      0.461 kg). Body volume (BV) tended to decrease (P = 0.08) from BV 1 (69.900 +/-
      0.449 L) to BV 2 (69.884 +/- 0.449 L). CONCLUSION: ADP using the Bod Pod appears
      to assess BD reliably; however, the observed CV suggests that multiple trials are
      necessary to detect small treatment effects.

PMID- 16888467
TI  - Accelerometry and heart rate as a measure of physical fitness: cross-validation.
AB  - PURPOSE: We recently reported on a new method to assess physical fitness, based
      on the combined use of accelerometry and heart rate (HR) registration. This study
      tested the validity of the prediction formula in a group of healthy young adults.
      METHODS: Twenty-six healthy subjects performed a maximal incremental test on a
      bicycle ergometer to determine VO2max. A triaxial accelerometer and a HR monitor
      were worn for 7 d under free-living conditions. The prediction formula developed
      in a previous experimental group (EXP) was applied on the cross-validation group
      (CV). RESULTS: No difference was found in subjects' characteristics between the
      EXP and CV groups except for accelerometer output (activity counts). Although
      measured VO2max could be predicted for 80% (P < 0.0001), a paired t-test showed a
      significant difference between measured and predicted VO2max (178 mL.min(-1); P =
      0.015). Because of the difference in activity between the EXP and the CV groups,
      all data were combined and sorted according to activity counts, then two new
      groups were formed. As a result, EXP and CV groups were created that did not
      significantly differ in activity or any other parameters. The formula developed
      in the new experimental group (R2 = 0.74; P < 0.0001) explained 72% (P < 0.0001)
      of the variation in VO2max in the cross-validation group, a paired t-test showed
      no difference between measured and predicted VO2max, and Bland-Altman plotting
      showed no systematic bias. CONCLUSION: Although a good correlation was seen
      between measured and predicted VO2max in the cross-validation group, care should
      be taken in applying the prediction formula on groups that differ in physical
      activity from the current study population.

PMID- 16888468
TI  - Effect of physical education and activity levels on academic achievement in
      children.
AB  - PURPOSE: This study was conducted to determine the effect of physical education
      class enrollment and physical activity on academic achievement in middle school
      children. METHODS: Participants were 214 sixth-grade students randomly assigned
      to physical education during either first or second semesters. Moderate and
      vigorous physical activity (MVPA) (number of 30-min time blocks) outside of
      school was assessed using the 3-d physical activity recall (3DPAR). The 3DPAR
      time blocks were converted to ordinal data with scores of 1 (no activity), 2
      (some activity), or 3 (activity meeting Healthy People 2010 guidelines). Academic
      achievement was assessed using grades from four core academic classes and
      standardized test scores (Terra Nova percentiles). RESULTS: Grades were similar
      regardless of whether students were enrolled in physical education during first
      or second semesters. Physical education classes averaged only 19 min of MVPA.
      Students who either performed some or met Healthy People 2010 guidelines for
      vigorous activity had significantly higher grades (P < 0.05) than students who
      performed no vigorous activity in both semesters. Moderate physical activity did
      not affect grades. Standardized test scores were not significantly related to
      physical education class enrollment or physical activity levels. CONCLUSION:
      Although academic achievement was not significantly related to physical education
      enrollment, higher grades were associated with vigorous physical activity,
      particularly activity meeting recommended Healthy People 2010 levels.

PMID- 16888469
TI  - Calculation of energy expenditure in women using the MET system.
AB  - PURPOSE: Interpretation of physical activity as energy expenditure requires
      adjustment for body size. This is usually accomplished by means of the MET
      system, which assumes a basal metabolic rate (BMR) of 4.184 kJ.kg(-1).h(-1) and,
      when the standard calculation is used, that the energy costs of different
      activities are proportional to BMR. These relationships may be altered by
      increases in percent total body fat (% TBF), and this paper examines
      relationships between % TBF and total energy expenditure (TEE) obtained using the
      standard and a proposed calculation. METHODS: Published data regarding body
      composition, physical activity (heart rate recording), and BMR in 11 American
      women (before and after weight gain) and in 15 Swedish women (before and during
      pregnancy) were used to calculate TEE. Reference estimates of TEE were obtained
      using doubly labeled water. RESULTS: In Swedish women, reference TEE minus
      standard TEE (MJ.24 h(-1)) was 1.37 +/- 1.29 (P < 0.01) before and 1.03 +/- 1.13
      (P < 0.05) during pregnancy. For proposed TEE these differences were 0.43 +/-
      1.63 (P > 0.05) and 0.31 +/- 1.28 (P > 0.05) (MJ.24 h(-1)), respectively. In
      American women before and after weight gain, reference TEE minus standard TEE
      (MJ.24 h(-1)) were 0.38 +/- 1.79 (P > 0.05) and 1.39 +/- 2.36 (P > 0.05),
      respectively, whereas the corresponding differences for proposed TEE (MJ.24 h(
      1)) were -0.52 +/- 2.20 (P > 0.05) and 0.21 +/- 2.36 (P > 0.05), respectively. In
      Swedish women before pregnancy and American women after weight gain (N = 26, BMI
      = 18-39), significant (P < 0.001) relationships were found for standard
      TEE/proposed TEE (y) versus % TBF, (x, r = -0.65) and versus BMI (x, r = -0.70).
      CONCLUSIONS: : In individuals with a TBF content typical for contemporary Western
      women, standard TEE is lower than proposed TEE. This bias increases as the TBF
      content of subjects increases. The results indicate that proposed TEE is more
      accurate than standard TEE, but this requires confirmation.

PMID- 16888470
TI  - Factors associated with physical activity in Canadian adults with diabetes.
AB  - INTRODUCTION: The purpose of this study was to identify key demographic and
      health factors associated with physical activity (PA) participation in adults
      with type 1 or type 2 diabetes. METHODS: Participants were adults > or = 18 yr of
      age living in the province of Alberta, Canada who were previously diagnosed with
      type 1 (N = 697) or type 2 (N = 1614) diabetes. Individuals were recruited from
      the Canadian Diabetes Association (Alberta) registry and through a random digit
      dialing protocol. Multiple and logistic regression models were employed to
      identify demographic and health factors related to PA levels, of which many to
      date have not been examined in this population. Analyses were conducted
      separately for type 1 and type 2 groups. RESULTS: Of those with type 1 and type 2
      diabetes, 63.7 and 71.9%, respectively, were not achieving recommended PA levels.
      For those with type 1, higher PA levels were associated with a younger age, being
      single, higher income, lower level of perceived disability, and not smoking. For
      the type 2 group, a younger age, male gender, higher education, higher income,
      lower body mass index, and lower level of perceived disability were associated
      with higher PA levels. CONCLUSIONS: Many of our results for both diabetes types
      are consistent with findings from other limited research in this domain. Contrary
      to previous research, however, a significant negative relationship was reported
      between body mass index and PA for the type 2 group. In addition, perceived
      disability was negatively associated with PA, which, to date, has not been
      reported in the literature with type 2 individuals. Research and practice related
      to physical activity promotion for this population should take into account
      specific demographic and health factors associated with PA.

PMID- 16888471
TI  - Population-based reference standards for cardiovascular fitness: an unanswered
      question.

PMID- 16888483
TI  - C. difficile: a menace in hospitals and homes alike.

PMID- 16888484
TI  - Gauging cardiovascular risk with the PLAC test.

PMID- 16888485
TI  - Using a spinal cord stimulator to ease chronic pain.

PMID- 16888486
TI  - Helping your patient manage Parkinson's disease.

PMID- 16888491
TI  - Enjoy "smarter" patient monitoring.

PMID- 16888489
TI  - Reducing medication errors by using applied technology.

PMID- 16888508
TI  - Pressure ulcers: a renewed awareness.

PMID- 16888510
TI  - Is your patient a suicide risk?

PMID- 16888511
TI  - First aid for sprains.

PMID- 16888512
TI  - Helping patients who need a permanent pacemaker.

PMID- 16888513
TI  - Mean ol' cuss-or pussycat?

PMID- 16888519
TI  - Tips for using implanted ports safely.

PMID- 16888522
TI  - Myths and facts... About ectopic pregnancy.

PMID- 16888514
TI  - New drugs 06, part II.

PMID- 16888523
TI  - Documenting preoperative education.

PMID- 16888524
TI  - Acute adrenal crisis.

PMID- 16888526
TI  - C. T. Brighton/ABJS workshop on orthopaedic education: editorial comment.

PMID- 16888527
TI  - Editorial: Development of certification in hand surgery. 1989.

PMID- 16888528
TI  - Fifty years of the American Board of Orthopaedic Surgery. 1990.

PMID- 16888529
TI  - Continuing competency in orthopaedics: the future of recertification.
AB  - The American Board of Orthopaedic Surgery implemented a recertification program
      in 1986. This process has expanded to include a number of examination pathways
      that take into account subspecialty practices. Over the past two decades, general
      competencies of physicians have been defined and programs for evaluation and
      maintenance of these competencies developed. In an effort to have a more
      continuous process rather than episodic examinations only, and stimulate lifelong
      learning and practice improvement, recertification is now undergoing
      transformation to a Maintenance of Certification program. Maintenance of
      Certification as a process will emphasize ongoing self-assessment and lifelong
      learning, with required components occurring more frequently during the 10 year
      recertification cycle. Patient satisfaction and communication surveys will be
      incorporated to provide feedback to physicians to improve practice performance.
      Case list reviews, with a focus on patient safety measures, will also be a new
      addition to the process.

PMID- 16888530
TI  - Effect of duty hour standards on burnout among orthopaedic surgery residents.
AB  - We surveyed orthopaedic surgery residents and faculty from two university
      training programs to quantify quality of life measures including burnout, general
      health, and relationship issues. Residents exhibited high levels of burnout and
      emotional exhaustion but only average levels of personal achievement, while
      faculty showed lower levels of burnout and emotional exhaustion with above
      average scores for personal achievement. Resident burnout was positively
      correlated with number of hours worked while faculty hours worked was inversely
      related to burnout. The survey was readministered two years after implementing
      the Accreditation Council on Graduate Medical Education guidelines on residency
      duty hours. At this time resident scores for personal accomplishment had
      improved, while scores for emotional exhaustion showed a strong trend towards
      decreasing, and depersonalization scores also showed a possible trend towards
      decreasing. Resident duty hour limitation was associated with improvement in
      objective measures of burnout.

PMID- 16888531
TI  - Institutional barriers to the orthopaedic clinician-scientist.
AB  - The clinician-scientist faces many career barriers that changes in medicine over
      the past two decades have accentuated. Political, socioeconomic, and cultural
      changes in medicine have increased financial pressures on physicians and
      hospitals, negatively impacting the ability of clinicians to pursue research
      activities. Examples of institutional barriers include pressure on physicians to
      increase clinical productivity to help offset rising costs and declining
      reimbursements, inadequate resources and structures to protect research time, a
      lack of consideration of the importance of spatial colocalization of interacting
      researchers and clinicians, insufficient focus on integrating clinician
      scientists into research teams, and inadequate accessibility of administrative
      research infrastructure. Lack of mentorship and role models in orthopaedics also
      contributes to the barriers confronting the clinician-scientist. A number of
      steps could be taken by institutions to positively influence orthopaedic
      clinician-scientist career development. Creation of research teams in which
      orthopaedic clinician-scientists can collaborate effectively with other
      researchers is a critical step, as is providing protected time free of clinical
      responsibilities to be devoted to research. Increased attention to physical co
      localization of the research activities of clinicians and scientists, and
      provision of research infrastructure at the department level are additional
      approaches that can be taken to ameliorate the institutional barriers to the
      orthopaedic clinician-scientist.

PMID- 16888532
TI  - Patellofemoral overstuff and its relationship to flexion after total knee
      arthroplasty.
AB  - Flexion is an important outcome variable after total knee arthroplasty.
      Traditionally, matched implant-bone resections of the distal and posterior
      aspects of the femur are used to prevent loss of knee flexion or extension.
      However, given limited implant sizes, resection of these portions of the femur
      may affect the shape of the knee. Variations in the anterior aspects of the femur
      along with implant size constraints may increase trochlear groove height in the
      anterior compartment, increase the arc that the extensor mechanism must travel,
      and thereby decrease passive flexion. We determined the trochlear groove height
      change in 55 patients after primary total knee arthroplasties. The thickness of
      the replaced lateral and medial anterior flanges increased by 1.1 +/- 2.6 mm and
      0.5 +/- 2.2 mm, respectively, whereas the change in trochlear groove thickness
      was 0 +/- 1.1 mm. We examined varying amounts of patellofemoral buildup in a
      cadaver model to observe the effect on passive range of motion of the knee. A 2
      mm and 4-mm buildup of the anterior cortex resulted in flexion loss of 1.8
      degrees and 4.4 degrees, respectively. The change in the shape of the anterior
      aspect of the femur may have small effects on flexion but they may not be
      clinically important.

PMID- 16888533
TI  - Painful toe in a 51-year-old man.

PMID- 16888535
TI  - Mini-incision total knee arthroplasty can increase risk of component
      malalignment.

PMID- 16888538
TI  - Retrosigmoid intradural suprameatal approach: advantages and disadvantages from
      an anatomical perspective.
AB  - OBJECTIVE: To assess the advantages and disadvantages of the retrosigmoid
      intradural suprameatal approach by studying the microsurgical anatomy. This study
      was performed primarily to assess the advantages of the retrosigmoid intradural
      suprameatal approach by measuring the amount of increased exposure it provides
      for lesions of the cerebellopontine and petroclival region as well as to identify
      the disadvantages of the approach. METHODS: Twenty sides of 10 cadaver heads
      (embalmed and injected) were dissected under x3 to x40 magnification. A standard
      retrosigmoid craniotomy was made. The cerebellopontine cistern was entered to
      expose the neurovascular structures, and the internal auditory canal was opened
      by drilling the margin of the internal auditory meatus. After this, the
      suprameatal tubercle was drilled, followed by additional drilling to resect the
      petrous apex. The trigeminal root was mobilized completely after opening Meckel's
      cave. During drilling, care was taken to preserve the posterior and superior
      semicircular canals, petrosal sinus, and the internal carotid artery. RESULTS:
      The approach enhanced the exposure of the cerebellopontine cistern and Meckel's
      cave. There was an additional exposure of 10.7 +/- 1.16 mm length of trigeminal
      nerve on the right side and an additional 10.7 +/- 1.25 mm on the left. This
      helped to mobilize and further retract the trigeminal root. Although it
      facilitated the view of the neurovascular structures medial to the internal
      acoustic meatus, the depth of exposure did not vary much from a traditional
      retrosigmoid approach nor did it increase the angle of exposure or the
      visualization of the clivus and more medially located structures. CONCLUSION:
      This approach is suitable for lesions mainly in the posterior fossa with some
      extension into the middle fossa in the anterolateral direction. The key benefits
      of this approach are the length of trigeminal nerve exposure and the subsequent
      mobilization that improves visualization of the structures medial to the internal
      auditory canal, to the petrous apex, Meckel's cave, and the posterior end of the
      cavernous sinus.

PMID- 16888539
TI  - The "yo-yo" technique to prevent cerebrospinal fluid rhinorrhea after anterior
      clinoidectomy for proximal internal carotid artery aneurysms.
AB  - OBJECTIVE: Resection of the anterior clinoid process is important for the
      exposure of aneurysms on clinoidal and supraclinoidal segments of the internal
      carotid artery. Cerebrospinal fluid (CSF) rhinorrhea can complicate anterior
      clinoidectomy when the optic strut is pneumatized and its removal communicates
      the subarachnoid space with the sphenoid sinus. We present a technique for
      repairing this defect and preventing CSF rhinorrhea. METHODS: A suture is secured
      around a strip of temporalis muscle, which is then pushed through the opening in
      the optic strut completely into the sphenoid sinus. The ends of suture that trail
      the muscle are used to retract the muscle from the sphenoid sinus back into the
      optic strut. The suture is trimmed and the repair is covered with sealant or
      fibrin glue. RESULTS: During an 8-year period in which 127 patients with proximal
      internal carotid artery aneurysms that required anterior clinoidectomy were
      treated, pneumatized optic struts were encountered in 14 patients (11%). Four
      patients were treated with the "yo-yo" technique, none of whom experienced CSF
      rhinorrhea. Before using this technique, 10 patients were managed with standard
      packing techniques (wax, muscle, and gel foam) and four of these patients
      subsequently experienced CSF rhinorrhea (40%). In these four patients, all
      required reoperation with either craniotomy and packing with pericranium (one
      patient), Couldwell-Luc procedure (one patient), or endoscopic transnasal
      obliteration of the sphenoid sinus with fat (two patients). CONCLUSION: The "yo
      yo" technique of tightly wedging a muscle plug into the optic strut proved to be
      simple, fast, and effective, preventing CSF rhinorrhea in all patients in whom it
      was applied. Although experience with this technique is limited, reversing the
      direction of packing and pulling muscle from the sphenoid sinus into the optic
      strut eliminated a complication that occurred in 40% of patients with standard
      packing techniques.

PMID- 16888540
TI  - A surgical technique for the removal of clinoidal meningiomas.
AB  - Clinoidal meningiomas, also referred to as medial or inner sphenoid wing
      meningiomas, are often difficult and challenging to remove completely and safely,
      especially when they become large enough to encircle, compress, or displace the
      adjacent critical neurovascular structures such as the optic nerve, the internal
      carotid artery and its branches, and the oculomotor nerve. In this article, the
      authors describe the detailed surgical technique used in their practice in
      addition to subtle nuances learned from their experience of operating on more
      than 40 patients with clinoidal meningiomas over the past several years. The
      primary goals of surgery are to achieve aggressive tumor removal with avoidance
      of intraoperative morbidity and, in addition, for those with preoperative
      compromised vision, to provide improvement in their visual function after
      surgery.

PMID- 16888541
TI  - The combined transmastoid retro- and infralabyrinthine transjugular transcondylar
      transtubercular high cervical approach for resection of glomus jugulare tumors.
AB  - Complex tumors OF the glomus jugulare present a surgical challenge because of
      their difficult location, extreme vascularity, and involvement with multiple
      cranial nerves. Modern microneurosurgical and cranial base techniques have
      enabled safe total removal of these complicated tumors. We describe a one-stage
      transjugular posterior infratemporal fossa approach for radical resection of
      glomus jugulare tumors located around the jugular foramen, the lower clivus, and
      the high cervical region from an anterolateral direction. This approach is a
      combination of transmastoid, suprajugular, transjugular, extreme lateral
      infrajugular transcondylar transtubercular, and high cervical approaches. Total
      exposure of the jugular foramen can be achieved, and multidirectional approaches
      can be performed, including infralabyrinthine/suprajugular,
      retrosigmoid/transcondylar/infrajugular, and transjugular exposures. Exposure of
      the vertical C7 segment of the infratemporal internal carotid artery and the
      lower clivus can be performed without permanent rerouting of the facial nerve.
      The details of this approach are described and illustrated in a stepwise fashion,
      and the microsurgical anatomy is reviewed.

PMID- 16888542
TI  - Preserving the ligamentum flavum in lumbar discectomy: a new technique that
      prevents scar tissue formation in the first 6 months postsurgery.
AB  - OBJECTIVE: Postoperative fibrosis is one of the most important causes of failed
      back surgery syndrome after lumbar disc surgery. Numerous natural and synthetic
      materials have been investigated as means to prevent or reduce postoperative
      scarring after these operations. Preservation of the ligamentum flavum for this
      purpose has not been studied in depth. A prospective, randomized, controlled
      clinical study was conducted. The aim was to present a new technique for
      preserving the ligamentum flavum during lumbar discectomy, and to evaluate
      whether this helps prevent or diminish postoperative fibrosis. METHODS: Twenty
      patients with unilateral L5-S1 disc herniation were randomly divided into two
      equal groups. Group A patients underwent classic microlumbar discectomy, and
      Group B patients underwent the same procedure but with preservation of the
      ligamentum flavum. Visual analog pain scale (VAPS) scores, Oswestry scale scores,
      and straight-leg raising angles were recorded preoperatively and at 6 months
      postoperatively. Differences between the pre-operative and postoperative findings
      for each group were statistically compared using the Wilcoxon test. Magnetic
      resonance imaging was also done at 6 months to assess the extent of postoperative
      fibrosis, and a "scarring grade" was recorded for each patient. The group
      findings for this were analyzed with Levene's test. RESULTS: Both groups'
      clinical parameters were significantly improved at 6 months postsurgery. In Group
      A, the mean pre- and postoperative VAPS scores were 9.2 and 3.2, respectively (P
      < 0.05); the corresponding mean Oswestry scale scores were 88 and 28.2,
      respectively (P < 0.05); and the corresponding mean straight-leg raising angles
      were 290 and 630, respectively (P < 0.05). In Group B, the mean pre- and
      postoperative VAPS scores were 9.2 and 2.6, respectively (P < 0.05); the
      corresponding mean Oswestry scores were 85.2 and 22.2, respectively (P < 0.05);
      and the corresponding mean straight-leg raising scores were 260 and 710,
      respectively (P < 0.05). The mean scarring grades in Groups A and B were 1.8 and
      1.0, respectively (P < 0.05). CONCLUSION: The groups both showed satisfactory
      clinical outcomes and the improvements were comparable; however, the group with
      preserved ligamentum flavum showed significantly less local fibrosis at 6 months
      postoperatively. The authors speculate that this surgical technique provides a
      physical protective barrier that can reduce or even eliminate fibrosis-related
      complications after lumbar disc surgery.

PMID- 16888543
TI  - Accuracy of pedicle screw placement for lumbar fusion using anatomic landmarks
      versus open laminectomy: a comparison of two surgical techniques in cadaveric
      specimens.
AB  - OBJECTIVE: We determined whether the accuracy of lumbar pedicle screw placement
      is optimized by performing a laminectomy before screw placement with screw entry
      point and trajectory being guided by pedicle visualization and palpation
      (Technique 1). This technique was compared with a technique using anatomic
      landmarks for pedicle screw placement (Technique 2). The biomechanical stability
      of the instrumented constructs, in the absence and presence of a laminectomy, was
      also compared. METHODS: Twelve L1-L3 specimens were harvested from fresh
      cadavers. The intact laminectomy and instrumented spines were biomechanically
      tested in flexion and extension, lateral bending, and axial rotation.
      Laminectomies were performed in six of the 12 specimens before pedicle screw
      placement using Technique 1. The remaining six specimens underwent pedicle screw
      and rod fixation using Technique 2. Computed tomographic images were obtained for
      all instrumented specimens. Deviation of the screws from the ideal entry point or
      trajectory was analyzed to quantitatively compare the two techniques. RESULTS:
      Computed tomographic analysis of the specimens showed that all screw placements
      were within the pedicles. Scatter plot analysis demonstrated that screws placed
      using Technique 2 were more likely to have the combination of entry points and
      trajectories medial to the ideal entry point and trajectory. Laminectomy did not
      weaken the final pedicle screw and rod-fixated constructs. CONCLUSION: All screw
      placements were grossly within the confines of the pedicles, regardless of
      technique, as evidenced by computed tomographic analysis. Furthermore, the
      anatomic landmark technique and the open laminectomy technique yielded
      biomechanically equivalent pedicle screw and rod-fixated constructs.

PMID- 16888544
TI  - Robotic virtual endoscopy: development of a multidirectional rigid endoscope.
AB  - INTRODUCTION: The use of neuroendoscopy has increased in the past 20 years.
      Despite an increase in the number of indications for use, novel adjuncts and
      modifications to existing endoscopes remain all but nonexistent. We introduce a
      robotic virtual endoscope with applications for neurosurgery that could serve as
      a novel step in the evolution of future endoscopic technologies. METHODS: Over
      the past 8 years, we have worked on the construction of a prototype endoscope
      with three degrees of freedom that was designed to allow for enhanced safety
      while maximizing the benefits of virtual field rendition and robotic control. We
      have developed a prototype to examine a cerebral ventricular model in vitro that
      functions via either a direct video- or computer-based interface. RESULTS:
      Assessment of viewing angulation with robotic feedback has verified the accuracy
      of the prototype. Models support the ability of the endoscope to localize regions
      identified via a software interface. CONCLUSION: The endoscope is a rigid virtual
      robotic endoscope that provides complete visual coverage of a three-dimensional
      space by controlling an adjustable viewing direction with three degrees of
      freedom.

PMID- 16888545
TI  - Applicability of an electrosurgical device based on electromagnetics in
      neurosurgery.
AB  - Because of electrical and thermal spread to healthy nervous tissue, the
      application of electrosurgical tools in neurosurgery has specific limitations.
      This is true for both bipolar and monopolar devices. These limitations are not
      inherent to an instrument in which action is based on electromagnetic interaction
      with human tissue. We evaluated the indications and the clinical applicability of
      a new radiofrequency electrosurgical unit that works on this biophysical
      principle. The system was found to be a useful addition for the resection of
      morphologically tougher tissue with keyhole approaches in which the ultrasound
      aspirator cannot easily be applied.

PMID- 16888546
TI  - Quantification of true in vivo (application) accuracy in cranial image-guided
      surgery: influence of mode of patient registration.
AB  - OBJECTIVE: Very few studies have attempted to quantify the true (application)
      accuracy of image-guidance systems during craniotomy. This is, in part, because
      of the lack of millimetric intraoperative targets to allow such measurements. Few
      in vivo studies have compared the influence of mode of patient registration on
      subsequent true accuracy. METHODS: Seven modes of patient registration (anatomic
      landmarks, 5 or 10 adhesive fiducials, bone-implanted fiducials [Stryker
      Leibinger], surface matching using 45 or 100 points over scalp convexity or
      nose/auditory meatus contours) were compared. Thirty patients were involved in
      the study. Millimetric targets (bone drill holes or deep 1-mm titanium hemoclips)
      were placed then localized and saved at surgery. These targets were then
      identified on postoperative volumetric computed tomography fused with operative
      data sets. Localization errors of the targets were measured for each registration
      on an optical image-guidance system (StealthStation). RESULTS: Only implanted
      cranial fiducials had a statistically significant accuracy advantage (1.7 +/- 0.7
      mm). All other registrations had similar accuracies (approximately 4.0 +/- 1.7
      mm) except anatomic landmarks, which were worse (4.8 +/- 1.9 mm). Calculated
      accuracies (root mean squared) had no predictive value for true (application)
      accuracies. CONCLUSION: Not surprisingly, application accuracy of image-guidance
      is worse without implanted cranial markers. Unexpectedly, there was no major
      difference in localization of deep targets between the other registrations tested
      in this study. Care must be taken when using image-guidance tools to consider
      error introduced by registration. Cranium-implanted fiducials should be
      considered when high accuracy and reproducibility are needed.

PMID- 16888547
TI  - Anatomical variations of the V2 segment of the vertebral artery.
AB  - OBJECTIVE: Our goal was to evaluate the incidence of anatomic variations of the
      V2 segment (from its entrance into the transverse canal to C2) of the vertebral
      artery. Ignoring such variations during anterior or lateral approach to the
      cervical spine can lead to inadvertent injury and potentially serious
      complications. METHODS: We studied the course of 500 vertebral arteries on 200
      magnetic resonance imaging and 50 contrast-enhanced computed tomographic scans.
      RESULTS: The vertebral artery entered the C6 transverse foramen in 93.0% of all
      specimens. An abnormal level of entrance was observed in 7.0% of specimens (35
      courses), with a level of entrance into the C3, C4, C5, or C7 transverse foramen,
      respectively, in 0.2% (n = 1; 2.9% of all anomalies), 1.0% (n = 5; 14.3% of all
      anomalies), 5.0% (n = 25; 71.4% of all anomalies), and 0.8% (n = 4; 11.4% of all
      anomalies) of all specimens. Seventeen (48.6%) abnormalities were right-sided and
      18 (51.4%) were left-sided. Thirty-one out of 250 patients (12.4%) had a
      unilateral anomaly and two had a bilateral anomaly (0.8%). In cases of abnormal
      entrance into the transverse foramen on computed tomographic images (n = 6), the
      area of the unfilled transverse foramens was significantly smaller than the
      contralateral filled foramen (P < 0.0001) and was significantly smaller than the
      filled foramen of all patients at the same level (P < 0.0001). In five patients
      (2.0%), the vertebral artery formed a medial loop either into an unusually large
      transverse foramen whose internal border was medial to the uncovertebral joint or
      into the intervertebral foramen. CONCLUSION: The incidence of anatomic variations
      of the vertebral artery V2 segment is high. Potentially dangerous conditions can
      be detected on preoperative imaging.

PMID- 16888548
TI  - Exposure of the cervical internal carotid artery: surgical steps to the cranial
      base and morphometric study.
AB  - OBJECTIVE: Several studies have reported on approaches to increase exposure of
      the distal cervical internal carotid artery (ICA), but these studies have neither
      systematically addressed the anatomic aspects nor quantified the additional
      exposure of each maneuver. We describe surgical steps to expose the ICA region,
      quantify the additional exposure of each operative step, and discuss ways to
      minimize surgical morbidity. METHODS: The ICA was exposed in 10 formalin-fixed
      cadaveric heads using the following four steps: 1) anterior sternocleidomastoid
      approach, 2) retroparotid dissection and division of the digastric muscle, 3)
      section of the styloid apparatus, and 4) mandibulotomy. After completion of each
      step, the most distal level of ICA exposure was marked with a hemoclip and
      segment lengths were measured between each clip. RESULTS: Sectioning of the
      digastric muscle and sectioning of the styloid apparatus provided the most
      significant exposure of the ICA (14.15 and 15.08 mm, respectively) with minimal
      risks. Mandibulotomy added 10.20 mm in length and 20.65 degrees in width, but is
      a maneuver that must be weighed against the heightened risk of morbidity.
      CONCLUSION: Surgical exposure of the distal cervical ICA is associated with
      relatively high morbidity that increases with higher levels of exposure. Staged
      maneuvers have been shown to increase ICA exposure, especially in our systematic
      approach. The number of steps required varies depending on the level of lesion.
      Complete understanding of the surgical anatomy is essential to minimize surgical
      morbidity and to develop surgical expertise.

PMID- 16888549
TI  - Speculum opening in transsphenoidal surgery.
AB  - OBJECTIVE: To assess the extent to which the transsphenoidal speculum can be
      safely opened at the face of and within the sphenoid sinus without risking damage
      to the optic nerves in the optic canals and at the orbital apex and the nerves
      coursing adjacent the walls of the sphenoid sinus. METHODS: The distance was
      measured between the optic nerves at the level of the anterior wall of the
      sphenoid sinus and 0.5 and 1.0 cm within the sinus. In addition, the distance
      between the middle turbinates and the contralateral optic canals was assessed
      because this turbinate is the largest structure blocking access to the sphenoid
      sinus in the transsphenoidal approach and tends to force the speculum away from
      the midline and toward the optic nerve in the contralateral side of the approach.
      RESULTS: Opening the transsphenoidal speculum at the anterior wall of the
      sphenoid sinus beyond 2.5 centimeters carries some risk of damaging the optic
      nerves and this distance narrows when the speculum opening is positioned inside
      the sphenoid sinus. Displacement of the speculum to one side by the middle
      turbinate places the speculum near the contralateral optic nerve and may be
      associated with optic nerve injury with lesser degrees of speculum opening.
      CONCLUSIONS: Careful attention should be directed to avoiding excessive opening
      of the transsphenoidal speculum at the anterior face of the sphenoid or within
      the sphenoid sinus.

PMID- 16888550
TI  - Posterior interhemispheric approach: surgical technique, application to vascular
      lesions, and benefits of gravity retraction.
AB  - OBJECTIVE: To review an experience with the posterior interhemispheric approach
      applied to vascular lesions in the posterior midline, to examine the effects of
      patient position and gravity retraction of the occipital lobe, and to identify
      circumstances requiring increased exposure by sectioning the falx and tentorium.
      METHODS: During a 6.5-year period, 46 posterior interhemispheric approaches were
      performed to treat 28 arteriovenous malformations, 10 dural arteriovenous
      fistulae, seven cavernous malformations, and one posterior cerebral artery
      aneurysm. Twenty-three patients were positioned prone and 23 patient were
      positioned laterally. RESULTS: A standard posterior interhemispheric approach was
      used in 38 patients, and the occipital bitranstentorial/falcine approach was used
      in seven patients. A contralateral occipital transfalcine approach was used with
      one thalamic cavernous malformation. All lesions were resected completely and/or
      obliterated angiographically, with good neurological outcomes in 83% of patients
      and no operative mortality. Blood loss was lower, operative durations were
      shorter, postoperative cerebral edema was decreased, and visual outcomes were
      improved in patients positioned laterally. CONCLUSION: The posterior
      interhemispheric approach, without additional dural cuts, is appropriate for most
      vascular lesions in the posterior midline. Gravity retracts the occipital lobes
      when patients are positioned laterally, enhancing operative exposure and reducing
      morbidity. Extension of the posterior interhemispheric approach to a
      transtentorial or transfalcine approach is required for falcotentorial dural
      arteriovenous fistulae and vein of Galen arteriovenous malformations, but is not
      usually necessary with cavernous malformations or other arteriovenous
      malformations.

PMID- 16888551
TI  - The endoscopic transnasal transsphenoidal approach for the treatment of cranial
      base chordomas and chondrosarcomas.
AB  - OBJECTIVE: We report our experience with endoscopic transsphenoidal or extended
      endoscopic transsphenoidal approaches for the treatment of cranial base lesions
      such as clival chordomas and chondrosarcomas. METHODS: Between May 1998 and April
      2004, 11 patients (four were recurrences because they previously had been treated
      with surgery and/or radiotherapy) underwent transnasal transsphenoidal endoscopic
      surgery for cranial base chordomas and chondrosarcomas at the Neurosurgical
      Department of Bellaria Hospital in Bologna. The transsphenoidal endoscopic
      approach and the ethmoid-pterygo-sphenoidal endoscopic approach were used to
      accomplish resection of the lesions involving the clivus and extending up to the
      parasellar region and to the petrous apex, or within the cavernous sinus.
      RESULTS: Patient follow-up periods ranged from 15 to 69 months (mean, 27 mo).
      Three patients died of chordoma progression at 20, 14, and 10 months,
      respectively, after endoscopic treatment. One patient experienced two
      recurrences; the first was treated using a new endoscopic approach, whereas the
      second, 1 year later, was treated by means of a far lateral approach. Four
      patients underwent postoperative proton beam radiotherapy, whereas one underwent
      a conventional megavoltage x-radiation therapy. However, postoperative
      radiotherapy was not administered in the two patients treated for cranial base
      chondrosarcoma. CONCLUSION: The flexibility of this new technique with respect to
      the classical microscopic transsphenoidal approach permits us to widen the
      horizon of surgical management of aggressive cranial base tumors such as clival
      chordomas and chondrosarcomas.

PMID- 16888552
TI  - The anterolateral partial vertebrectomy approach for ventrally located cervical
      intramedullary cavernous angiomas.
AB  - OBJECTIVE: We report three cases with ventral cervical intramedullary cavernous
      angiomas. An anterolateral partial vertebrectomy was performed to surgically
      approach and successfully resect these lesions. MATERIALS AND METHODS: All three
      patients presented with numbness in the upper extremities and investigation
      revealed a cavernous angioma on the ventral aspect of the spinal cord in each
      case. The lesion was exposed by an anterolateral partial vertebrectomy in all
      cases. Postoperative stabilization was achieved by using autografted iliac bone
      in all patients. In two patients, locking screws and plates were also used.
      RESULTS: Complete resection of the cavernous angioma was performed in all
      patients. There was symptomatic relief in all cases, and there was no
      postoperative morbidity. CONCLUSION: Anterolateral partial vertebrectomy provides
      direct exposure and is probably an ideal approach for selected cases with
      ventrally located intramedullary cavernous angiomas.

PMID- 16888553
TI  - The role of free flaps in the treatment of persistent scalp osteomyelitis.
AB  - OBJECTIVE: To evaluate the efficacy of the combination of an extensive surgical
      debridement and simultaneous free flap repair in case of troublesome cranial
      osteomyelitis. METHODS: Five patients with persistent, frontal bone osteomyelitis
      were treated with surgical debridement of the infected bone and reconstruction
      with a free flap. In all patients, osteomyelitis occurred after neurosurgical
      procedures and lasted from 1 to 7 years. A latissimus dorsi muscle flap with a
      split skin graft has been performed. RESULTS: No flap failure occurred and donor
      site morbidity was negligible. No signs of osteomyelitis or soft tissue infection
      were observed during the mean follow-up period of 3.2 years. Furthermore, the
      contour of the cranium could be preserved without a need for bone grafts or
      implants. CONCLUSION: In our experience, the combination of an extensive surgical
      debridement and a free flap transfer is demonstrated to be an effective treatment
      for "chronic" osteomyelitis of the cranium.

PMID- 16888554
TI  - The impact of petrosal vein preservation on postoperative auditory function in
      surgery of petrous apex meningiomas.
AB  - OBJECTIVE: The importance of preserving the superior petrosal vein has received
      increasing attention in the surgical treatment of pathologies involving the
      petrous apex. Recent reports have associated postoperative auditory nerve
      dysfunction with petrosal vein sacrifice. However, there is no systematic
      clinical study available thus far focusing on the postoperative auditory function
      after petrosal vein obliteration. METHODS: In 55 patients with meningiomas
      involving the petrous apex, pre- and intraoperative findings including petrosal
      vein sectioning were analyzed retrospectively concerning their impact on
      postoperative auditory function. RESULTS: The petrosal vein was preserved in 26
      (47%) cases. In 27 (49%) cases, this vein was not preserved. Hearing loss
      occurred in 11% of all cases. In the preserved-vein group, postoperative hearing
      loss occurred in 3 of 26 (11%) cases and in the sacrificed-vein group in 3 of 27
      (11%) cases. CONCLUSION: Sacrifice of the petrosal vein during surgery of petrous
      apex meningiomas seems not to have an impact on postoperative auditory function.

PMID- 16888555
TI  - Three-dimensional computed tomographic analysis of the relationship between the
      arcuate eminence and the superior semicircular canal.
AB  - OBJECTIVE: The location of the superior semicircular canal (SSC) is often
      determined intraoperatively based on its topographic association with the arcuate
      eminence (AE). This determination is not always possible because of the potential
      variability in the relationship between these two structures. The goal of this
      study was to describe the three-dimensional (3-D) relationship between the AE and
      SSC using 3-D computed tomography (CT) and to evaluate the utility of 3-D CT for
      preoperative planning for surgical approaches to the middle cranial fossa.
      METHODS: We studied 11 patients (22 sides) radiographically using 0.8- to 1-mm
      thick reconstructed CT images. A standard set of structural relationships was
      measured between the AE, SSC, and other regional landmarks. RESULTS: 3-D CT
      clearly demonstrated the relationships between traditional landmarks along the
      petrous ridge and middle cranial fossa. The relationship between the arcuate
      eminence and SSC was found to be highly variable. The average distance between
      the tips of the two structures was found to be 5.7 mm (range, 2.7-10.4 mm).
      CONCLUSIONS: There is significant variability in the relationship between the AE
      and the SSC. The AE is not a consistent or reliable landmark for identifying the
      precise position of the SSC. Detailed preoperative information regarding the
      relationship between the AE, SSC, and other bony landmarks can be easily and
      quickly assessed using 3-D CT.

PMID- 16888557
TI  - C2 crossing laminar screws: cadaveric morphometric analysis.
AB  - OBJECTIVE: C2 screw fixation through the pars or pedicle involves a small but
      finite risk of vertebral artery injury. Recently, C2 crossing laminar screws were
      described as a method for rigid fixation of the axis. This technique, confined to
      the dorsal aspect of C2, presents minimal chance of injury to the neighboring
      neural or vascular structures. METHODS: Morphometric analysis was performed on 38
      cadaveric spines obtained from the Keck School of Medicine at the University of
      Southern California. Critical measurements were determined for screw entry
      points, trajectories, and lengths for application of the technique, as described
      by Wright, using 3.5 and 4.0 mm screws. RESULTS: The average maximal screw length
      was 32 mm with a range of 27 to 37 mm. The minimal total laminar cross sectional
      area averaged 75 mm2, and the cancellous bone cross sectional area averaged 39
      mm2. The minimal laminar cross sectional diameter was determined to be too small
      to accommodate a 3.5-mm diameter screw, assuming a 1 mm tolerance on each side,
      in 16 sides of 14 specimens, and to be too small to accommodate a 4.0 mm diameter
      screw, assuming a 1 millimeter tolerance, in 32 sides of 18 specimens.
      CONCLUSION: C2 laminar screw placement is straightforward and carries little risk
      of injury to the neural and vascular structures as long as the implants remain
      intraosseous. However, the highly variable thickness of the C2 lamina
      necessitates preoperative computed tomographic scanning to ensure that the
      patient's anatomy can accommodate screws entirely within the bone.

PMID- 16888556
TI  - The endoscopic extended transsphenoidal approach for craniopharyngiomas.
AB  - OBJECTIVE: The endoscope has recently been applied to the supradiaphragmatic
      transsphenoidal approach, but only case reports dealing with different
      pathological features have been described. The authors present their experience
      with this technique in 10 patients with craniopharyngiomas. METHODS: A pure
      endoscopic endonasal technique was used. From November 1998 through May 2005,
      four males and six females with a craniopharyngioma, either purely
      supradiaphragmatic (six patients) or with a significant suprasellar component
      (four patients), were treated. The tumors had a mean diameter of 2.9 cm (range, 1
      4 cm); four patients had a major prechiasmatic component and six had a
      retrochiasmatic one. RESULTS: Seven total, one subtotal, and two partial
      resections were obtained. Vision symptoms improved significantly in six out of
      eight patients. Endocrine function did not improve after surgery, and diabetes
      insipidus was the most frequent deficit, although it was transient in five out of
      eight patients. Cerebrospinal fluid leak was the most frequent complication and
      required reoperation in two patients. Postoperative obesity occurred in two
      patients. No recurrence has yet been documented in the total resection group. The
      mean follow-up period is 37 months (range, 3-75 mo). CONCLUSION: The endoscopic
      technique allows results comparable with the best microscopic series. We think
      that this technique increases the safety of the procedure because of improved
      vision. Further studies are required to better define the exact location of the
      tumor with respect to the arachnoidal plane, the extra-arachnoidal
      craniopharyngioma being the most suitable for a radical removal using a
      transsphenoidal supradiaphragmatic approach.

PMID- 16888558
TI  - A novel endoscopic technique in treating single nerve entrapment syndromes with
      special attention to ulnar nerve transposition and tarsal tunnel release:
      clinical application.
AB  - OBJECTIVE: To describe a simple retractor integrated endoscopic technique for
      treating idiopathic solitary compression neuropathies with special attention to
      the anterior transposition of the ulnar nerve and tarsal tunnel release, and to
      present the clinical results. METHODS: Eleven patients with ulnar sulcus
      syndrome, eight with tarsal tunnel syndrome, and one with meralgia paraesthetica
      (seven females and 13 males; age range, 12-64 yr) were treated with endoscopic
      anterior ulnar nerve transposition and in situ decompression of the tibial (eight
      patients) and lateral femoral cutaneous nerves (one patient), respectively. The
      selection criteria were: classical nerve compression symptoms, failed
      conservative treatment, abnormal electrophysiology, and a nonviolated anatomic
      region. The degree of nerve compression (after Dellon) was rated as moderate in
      five out of 20 patients and as severe in 15 out of 20 patients.
      Electrophysiological studies were conducted independently by physicians
      specializing in these techniques. Postoperative recovery was evaluated according
      to the nine-point Bishop rating system. RESULTS: Of the 11 patients with anterior
      ulnar nerve transposition, seven scored excellent, three scored good, and one
      scored fair (mean follow-up, 15.5 mo; range, 6-27 mo). Five patients with tarsal
      tunnel release scored excellent and three scored good (mean follow-up, 10.1 mo;
      range, 3-24 mo). The patient with meralgia paraesthetica showed an excellent
      score at 28 months after surgery. There were no technical or postoperative
      complications. None of the operations had to be converted to open surgery.
      CONCLUSION: We describe a new endoscopic technique for transposing the ulnar
      nerve and decompressing the tibial nerve. This technique could be extrapolated to
      release other single nerve entrapments. The simplicity of the technique, and our
      preliminary clinical results, may encourage other groups to adapt this method.

PMID- 16888559
TI  - Eyebrow surgery: the supraciliary craniotomy: technical note.
AB  - OBJECTIVE: Many approaches have been recommended for the surgical treatment of
      anterior and middle cranial fossa lesions. The frontobasal approach and its many
      modifications have been proposed and developed for such situated lesions. An
      alternative approach is the frontolateral craniotomy through a supraciliary skin
      incision. METHODS: This minimally invasive technique, a 2.5 x 3.0 cm craniotomy,
      just above the eyebrow through a supraciliary incision, is a simple but elegant
      modification of the traditional approach to the anterior cranial fossa. RESULTS:
      A step-by-step description of the approach is offered in this report to
      facilitate a clear understanding of the lesions treatable with this minimally
      invasive technique. CONCLUSION: The supraciliary frontolateral keyhole craniotomy
      is a minimally invasive cosmetic approach that provides excellent exposure to a
      variety of intracranial lesions. This approach cannot be used for all
      intracranial pathologies, but is recommended for many anterior and middle cranial
      fossa lesions.

PMID- 16888560
TI  - Removal of an orbital apex hemangioma using an endoscopic transethmoidal
      approach: technical note.
AB  - OBJECTIVE: The posterior orbit contains a number of important and vulnerable
      structures, including the optic nerve, the ophthalmic artery and vein, and the
      ocular muscles and their motor nerves, which makes surgical access to the lesion
      in this region quite difficult. Transfrontal, transfrontal-ethmoidal, and
      transmaxillary procedures have the disadvantage of possible injuries to a number
      of nontumor structures, whereas an endoscopic transethmoidal approach is a
      minimally invasive surgery for the retrobulbar lesions. Retrobulbar cavernous
      hemangioma was successfully removed by a transethmoidal approach. METHODS: Tumor
      removal was performed in a patient with an intraconal cavernous hemangioma of
      approximately 15 mm in diameter. By a transethmoidal approach, the medial
      inferior part of the orbit, as well as the apex of the orbit, were clearly
      visualized after endonasal ethmoidectomy. After the removal of the medial orbital
      bone, the orbital periosteum was incised and elevated. By elevating the orbital
      fat, the tumor could be identified separately from the orbital contents. RESULTS:
      Cavernous hemangioma at the orbital apex was removed without complications.
      CONCLUSION: An endoscopic transethmoidal approach, which requires no skin
      incision, is a minimally invasive surgery for retrobulbar orbital tumor, leading
      to excellent cosmetic results with less bleeding.

PMID- 16888561
TI  - The expanded endonasal approach for an endoscopic transnasal clipping and
      aneurysmorrhaphy of a large vertebral artery aneurysm: technical case report.
AB  - OBJECTIVE: Aneurysms of the vertebral artery are rare, comprising less than 5% of
      all aneurysms. They can present with subarachnoid hemorrhage, medullary
      compression, and cranial neuropathies. In consideration of their surrounding
      regional anatomy, they present a formidable surgical challenge to the
      neurosurgeon using traditional techniques. Recent advances in endoscopic
      transnasal surgery have provided an additional approach for the treatment of
      these difficult lesions. CLINICAL PRESENTATION: We present a case of a large
      vertebral artery aneurysm causing mass effect on the medulla. Initial treatment
      consisted of endovascular trapping of the aneurysm; however, because of concerns
      that the remaining aneurysm and intraluminal thrombus was causing mass effect and
      continued brainstem compression, a decompressive procedure was required.
      INTERVENTION: After the endovascular trapping, the patient underwent a completely
      endoscopic transnasal surgical clipping and aneurysmorrhaphy. After exposure of
      the aneurysm, distal and proximal clips were applied transnasal, and the
      aneurysmorrhaphy completed using suction and ultrasonic aspiration. CONCLUSION:
      In consideration of their surrounding regional anatomy, aneurysms of the
      vertebral artery present a formidable surgical challenge to the neurosurgeon.
      Although endovascular techniques have proven to be extremely valuable for the
      treatment of these lesions, they are limited when patients have significant mass
      effect with brainstem compression or cranial neuropathy. Advances in endoscopic
      transnasal surgery have provided an additional approach for the treatment of
      these difficult lesions. This case report represents, to our knowledge, the first
      literature report of a transnasal endoscopic aneurysm clipping and thrombectomy.

PMID- 16888562
TI  - Treatment of a partially thrombosed giant aneurysm of the vertebral artery by
      aneurysm trapping and direct vertebral artery-posterior inferior cerebellar
      artery end-to-end anastomosis: technical case report.
AB  - OBJECTIVE: The purpose of this article is to focus for the first time on the
      operative management of a direct vertebral artery (VA)-posterior inferior
      cerebellar artery (PICA) end-to-end anastomosis in a partially thrombosed giant
      VA-PICA-complex aneurysm and to underline its usefulness as an additional
      treatment option. METHODS: The operative technique of a direct VA-PICA end-to-end
      anatomosis is described in detail. The VA was entering the large aneurysm sack.
      Distally, the PICA originated from the aneurysm sack-VA-complex. The donor and
      recipient vessel were cut close to the aneurysm. Whereas the VA was cut in a
      straight manner, the PICA was cut at an oblique 45-degree angle to enlarge the
      vascular end diameter. Vessel ends were flushed with heparinized saline and
      sutured. The thrombotic material inside the aneurysm sack was removed and the
      distal VA clipped, leaving the anterior spinal artery and brainstem perforators
      free. RESULTS: The patient regained consciousness without additional morbidity.
      Magnetic resonance imaging scans revealed a completely decompressed brainstem
      without infarction. The postoperative angiograms demonstrated a good filling of
      the anastomosed PICA. CONCLUSION: Despite the caliber mistmatch of these two
      vessels the direct VA-PICA end-to-end anastomosis provides an accurate
      alternative in addition to other anastomoses and bypass techniques, when donor
      and recipient vessels are suitable and medullary perforators do not have to be
      disrupted.

PMID- 16888563
TI  - Treatment of a superior sagittal sinus dural arteriovenous fistula with Onyx:
      technical case report.
AB  - OBJECTIVE: The endovascular treatment of a complex superior sagittal sinus dural
      arteriovenous fistula with ethylene vinyl alcohol copolymer (Onyx) in one session
      is described. CLINICAL PRESENTATION: A 54-year-old man presented with dizziness
      and a bruit. A cerebral angiogram demonstrated a superior sagittal sinus dural
      arteriovenous fistula with a patent superior sagittal sinus that was supplied via
      multiple branches of the external carotid arteries bilaterally and the left
      anterior and middle cerebral arteries. Drainage was mainly through the superior
      sagittal sinus and, only in part, retrogradely through the cortical veins. A
      decision was made to proceed with endovascular treatment followed by surgery.
      INTERVENTION: Transarterial injection of one pedicle of middle meningeal artery
      on both sides with Onyx resulted in complete obliteration of the dural supply and
      some of the pial supply to the malformation without complications. The superior
      sagittal sinus remained patent. Based on this result, surgical treatment was
      cancelled. The residual pial supply had disappeared by the 10-month angiographic
      follow-up examination and the patient remained neurologically intact and without
      symptoms. CONCLUSION: Definitive treatment may be attained with Onyx in dural
      arteriovenous fistulas. The potential of Onyx for use as a permanent embolic
      agent in dural arteriovenous fistulae needs to be investigated.

PMID- 16888565
TI  - [Technology: always more efficient].

PMID- 16888564
TI  - Use of the Amplatzer vascular plug as an anchoring scaffold for coil-mediated
      parent vessel occlusion: technical case report.
AB  - OBJECTIVE: Parent vessel sacrifice is a useful treatment strategy for fusiform
      intracranial aneurysms. Originally performed using the detachable silicone
      balloon, endovascular arterial occlusion is currently achieved using coils, a
      process which can be limited by coil mass migration. METHODS: We demonstrate the
      use of the Amplatzer vascular plug as a fixed anchor within the target parent
      vessel to facilitate coil-mediated occlusion, especially in vascular segments not
      encased by a bony canal. The technique was used successfully in two patients: a
      90-year-old woman presenting with IIIrd and VIth cranial nerve palsy from a
      fusiform left cavernous internal carotid aneurysm and a 44-year-old man with
      distal thromboemboli from a fusiform dissecting-type right vertebral artery
      involving the origin of the posterior inferior cerebellar artery. RESULTS: Both
      patients were treated successfully with proximal parent vessel occlusion using
      coils after deployment of an Amplatzer vascular plug proximal to the target
      lesion. With the Amplatzer device acting as a fixed anchor in the parent vessel,
      coils were deployed proximally in a compact configuration. After deployment of
      the vascular plugs and coils, hermetic occlusion of the parent vessel was
      documented angiographically. CONCLUSION: The Amplatzer vascular plug can
      facilitate coil occlusion of large cervical vessels by acting as a focal coil and
      embolic material immobilizer, which can prevent coil mass migration and lead to
      improved packing density.

PMID- 16888566
TI  - [Cardiac imaging].

PMID- 16888567
TI  - [Imaging of the GI tract].

PMID- 16888568
TI  - [Gynecological imaging].

PMID- 16888569
TI  - [Imaging of the liver].

PMID- 16888570
TI  - [Oncologic imaging: current status].

PMID- 16888571
TI  - [ENT imaging].

PMID- 16888572
TI  - [Osteo-articular imaging].

PMID- 16888573
TI  - [Breast imaging].

PMID- 16888574
TI  - [Pulmonary imaging].

PMID- 16888575
TI  - [Urology].

PMID- 16888576
TI  - [Vascular and interventional imaging].

PMID- 16888577
TI  - [Informatics and medical imaging: a year of transition?].

PMID- 16888578
TI  - [Neuroradiology].

PMID- 16888580
TI  - [Pediatric radiology].

PMID- 16888579
TI  - [Interventional radiology].

PMID- 16888581
TI  - [Ultrasound imaging].

PMID- 16888582
TI  - [MRI: multiplicity of platforms and applications!].

PMID- 16888583
TI  - [Sonography: consolidation and new perspectives].

PMID- 16888584
TI  - [CT: status on multi-detector row scanners!!!].

PMID- 16888585
TI  - [Nuclear medicine: from nuclear medicine to molecular imaging].

PMID- 16888586
TI  - [Digital imaging: update on detectors].

PMID- 16888587
TI  - [PACS or the patient's radiological files].

PMID- 16888588
TI  - [What is your diagnosis? Vertebral fracture due to ankylosing spondylarthritis].

PMID- 16888589
TI  - [What is your diagnosis? Multifocal osseous tuberculosis confirmed by bone
      biopsy].

PMID- 16888590
TI  - [What is your diagnosis? Partial right abnormal pulmonary venous return with
      intra-atrial venous sinus communication].

PMID- 16888591
TI  - [What is your diagnosis? Von Hippel-Lindau disease].

PMID- 16888592
TI  - [What is your diagnosis? Rheumatoid purpura with digestive involvement].

PMID- 16888593
TI  - [What is your diagnosis? Brown tumor of the right maxillary sinus].

PMID- 16888594
TI  - [What is your diagnosis? Frontal solitary plasmacytoma].

PMID- 16888595
TI  - [What is your diagnosis? Hypertrophic degeneration of the olivary nucleus].

PMID- 16888596
TI  - [What is your diagnosis? Hydatid cyst of the arm].

PMID- 16888597
TI  - [Laparoscopic appendectomy or evidence based medicine under fire].

PMID- 16888598
TI  - [Air in the portal venous system: radiologic differential diagnosis and etiology
      specific treatment].
AB  - Portal venous air is a rare but potentially grave radiologic sign. The routine
      use of abdominal CT and ultrasound allows the detection of minimal amounts of
      portal air, often at an asymptomatic stage. The first diagnosis to consider by
      both frequency and gravity is intestinal necrosis which carries a 75% mortality.
      And yet there are also benign etiologies of portal venous air, usually
      asymptomatic, which do not require surgical intervention. The aim of this study
      is to describe the differential diagnosis of portal venous air and its clinical
      management.

PMID- 16888599
TI  - [Management of choledocholithiasis].
AB  - Choledocholithiasis is a not uncommon and potentially grave condition which
      requires a well-adapted approach. Echo endoscopy and biliary MRI have improved
      the ability to make the diagnosis non-invasively, but intraoperative
      cholangiography remains the most accurate study. A surgical approach permits
      simultaneous treatment of both choledocholithiasis and the associated
      cholecystolithiasis; laparoscopic common duct exploration has been more
      frequently performed through a laparoscopic approach in recent years, but this
      procedure requires specific equipment and surgical experience. In most
      circumstances, surgery should be preferred to endoscopic clearance of the common
      duct, but endoscopy may be preferred in the setting of severe cholangitis or
      pancreatitis. The importance of a systematic search for asymptomatic
      choledocholithiasis is once again emphasized.

PMID- 16888600
TI  - [Appendicitis: yes or no to laparoscopic approach?].
AB  - Whether or not there is a benefit to laparoscopy versus open surgery in the
      management of acute appendicitis remains a subject of controversy despite the
      publication of numerous randomized studies. Operative time is longer for the
      laparoscopic approach. The incidence of abdominal wall abscess is decreased for
      laparoscopy but the incidence of deep intra-abdominal abscess may be increased,
      especially in the case of complicated appendicitis. Post-operative pain is
      diminished and resumption of normal activity is quicker with the laparoscopic
      approach. Hospitalization is shorter but the cost of hospital care is higher;
      nevertheless, the global cost may be less - particularly for patients whose
      return to work is hastened by a laparoscopic approach. Laparoscopy diminishes the
      number of normal appendectomies, particularly in women of reproductive age where
      the diagnosis may be unclear. Laparoscopic appendectomy is practicable and has
      advantages over open appendectomy under certain circumstances. These advantages
      are most evident in the young female, the working patient, and the obese patient.
      Overall, the advantages of laparoscopy are, at best, modest and clinical benefit
      is not always demonstrable. The risk of deep abscess, particularly in patients
      with perforated or gangrenous appendicitis, remains an unknown and should be
      evaluated by further studies.

PMID- 16888601
TI  - [Laparoscopic surgery. The recommendations of specialty societies in 2006 (SFCL
      SFCE)].

PMID- 16888602
TI  - [Rectocele repair by perineal approach with mesh prosthesis].

PMID- 16888603
TI  - [Right hepatectomy by the anterior approach].

PMID- 16888604
TI  - [Ruptured infra-renal abdominal aortic aneurysm].

PMID- 16888605
TI  - [Acute gastric necrosis].

PMID- 16888606
TI  - [Tumor of the third portion of the duodenum].

PMID- 16888608
TI  - [Etiology of liver abscess. 2. A mysterious etiology...].

PMID- 16888607
TI  - [Etiology of liver abscess. 1. A rare etiology...].

PMID- 16888609
TI  - [Hernia of Petit's Triangle (lumbar hernia): laparoscopic repair].

PMID- 16888610
TI  - Pertussis outbreak in an Amish community--Kent County, Delaware, September 2004
      February 2005.
AB  - Vaccine-preventable disease outbreaks continue to occur among undervaccinated
      populations in the United States, including contained religious communities. The
      Amish practice separation from the world through group solidarity and caring for
      their own. Amish religious doctrine does not prohibit vaccination; however,
      coverage levels for routine childhood vaccination remain low in many Amish
      communities. This report describes an outbreak of pertussis in an Amish community
      in Kent County, Delaware, during September 2004-February 2005, that resulted in
      345 cases and affected primarily preschool-aged children. The outbreak
      underscores the need to promote vaccination in Amish communities through
      culturally appropriate strategies, such as education and outreach to community
      leaders.

PMID- 16888611
TI  - Secondary school health education related to nutrition and physical activity-
      selected sites, United States, 2004.
AB  - Eating a healthful diet and engaging in physical activity have important health
      benefits for youths, such as reducing overweight, a condition that affected 17%
      of those aged 12-19 years during 2003-2004. School health education that includes
      information about nutrition and physical activity is an important component of a
      comprehensive approach to improving dietary behavior, reducing sedentary
      behavior, and increasing physical activity among youths. A previous study
      suggested that professional development for health education teachers helps
      ensure the quality of health education instruction. To identify which nutrition
      and physical activity topics are being taught in school health education courses
      and what percentage of lead health education teachers have received professional
      development on nutrition and physical activity, CDC analyzed data from the 2004
      School Health Profiles for public secondary schools (i.e., middle, junior high,
      and senior high schools) serving students in grades 6-12 in 25 states and 10
      large urban school districts. This report summarizes the results of that
      analysis, which indicated that in 2004, approximately one half to three fourths
      of schools in the participating states and school districts taught all 15
      nutrition and dietary behavior topics listed in the School Health Profiles
      questionnaire in a required health education course, and approximately one third
      to two thirds taught all 12 physical activity and fitness topics. State and local
      education agencies should continue to encourage schools to provide education on
      nutrition and physical activity as part of a coordinated school health program
      and promote staff development for health education teachers.

PMID- 16888612
TI  - Sexually transmitted diseases treatment guidelines, 2006.
AB  - These guidelines for the treatment of persons who have sexually transmitted
      diseases (STDs) were developed by CDC after consultation with a group of
      professionals knowledgeable in the field of STDs who met in Atlanta, Georgia,
      during April 19-21, 2005. The information in this report updates the Sexually
      Transmitted Diseases Treatment Guidelines, 2002 (MMWR 2002;51[No. RR-6]).
      Included in these updated guidelines are an expanded diagnostic evaluation for
      cervicitis and trichomoniasis; new antimicrobial recommendations for
      trichomoniasis; additional data on the clinical efficacy of azithromycin for
      chlamydial infections in pregnancy; discussion of the role of Mycoplasma
      genitalium and trichomoniasis in urethritis/cervicitis and treatment-related
      implications; emergence of lymphogranuloma venereum protocolitis among men who
      have sex with men (MSM); expanded discussion of the criteria for spinal fluid
      examination to evaluate for neurosyphilis; the emergence of azithromycin-
      resistant Treponema pallidum; increasing prevalence of quinolone-resistant
      Neisseria gonorrhoeae in MSM; revised discussion concerning the sexual
      transmission of hepatitis C; postexposure prophylaxis after sexual assault; and
      an expanded discussion of STD prevention approaches.

PMID- 16888613
TI  - The Mll-Een knockin fusion gene enhances proliferation of myeloid progenitors
      derived from mouse embryonic stem cells and causes myeloid leukaemia in chimeric
      mice.
AB  - Rearrangement of the mixed lineage leukaemia (MLL) gene with extra eleven
      nineteen (EEN) was previously identified in an infant with acute myeloid
      leukaemia. Using homologous recombination, we have created a mouse equivalent of
      the human MLL-EEN allele and showed that when Mll(Een/+) embryonic stem (ES)
      cells were induced to differentiate in vitro into haemopoietic cells, there was
      increased proliferation of myeloid progenitors with self-renewal property. We
      also generated Mll(Een/+) chimeric mice, which developed leukaemia displaying
      enlarged livers, spleens, thymuses and lymph nodes owing to infiltration of
      Mll(Een/+)-expressing leukemic cells. Immunophenotyping of cells from enlarged
      organs and bone marrow (BM) of the Mll(Een/+) chimeras revealed an accumulation
      of Mac-1+/Gr-1- immature myeloid cells and a reduction in normal B- and T-cell
      populations. We observed differential regulation of Hox genes between myeloid
      cells derived from Mll(Een/+) ES cells and mouse BM leukemic cells which
      suggested different waves of Hox expression may be activated by MLL fusion
      proteins for initiation (in ES cells) and maintenance (in leukemic cells) of the
      disease. We believe studies of MLL fusion proteins in ES cells combined with in
      vivo animal models offer new approaches to the dissection of molecular events in
      multistep pathogenesis of leukaemia.

PMID- 16888614
TI  - JAK2 V617F mutation analysis in different myeloid lineages (granulocytes,
      platelets, CFU-MK, BFU-E and CFU-GM) in essential thrombocythemia patients.

PMID- 16888615
TI  - Novel FISH probes designed to detect IGK-MYC and IGL-MYC rearrangements in B-cell
      lineage malignancy identify a new breakpoint cluster region designated BVR2.
AB  - Detection of translocations involving MYC at 8q24.1 in B-cell lineage
      malignancies (BCL) is important for diagnostic and prognostic purposes. However,
      routine detection of MYC translocations is often hampered by the wide variation
      in breakpoint location within the MYC region, particularly when a gene other than
      IGH, such as IGK or IGL, is involved. To address this issue, we developed and
      validated four fluorescence in situ hybridization (FISH) probes: two break apart
      probes to detect IGK and IGL translocations, and two dual-color, dual-fusion FISH
      (D-FISH) probes to detect IGK-MYC and IGL-MYC. MYC rearrangements (four IGK-MYC,
      12 IGL-MYC and four unknown partner gene-MYC) were correctly identified in 20 of
      20 archival BCL specimens known to have MYC rearrangements not involving IGH.
      Seven specimens, all of which lacked MYC rearrangements using a commercial
      IGH/MYC D-FISH probe, were found to have 8q24 breakpoints within a cluster region
      >350-645 kb 3' from MYC, provisionally designated as Burkitt variant
      rearrangement region 2 (BVR2). FISH is a useful ancillary tool in identifying MYC
      rearrangements. In light of the discovery of the distally located BVR2 breakpoint
      cluster region, it is important to use MYC FISH probes that cover a breakpoint
      region at least 1.0 Mb 3' of MYC.

PMID- 16888617
TI  - The current status of reduced-intensity allogeneic hematopoietic stem cell
      transplantation for multiple myeloma.
AB  - Of all the treatment modalities employed to control multiple myeloma, only
      allogeneic hematopoietic stem cell transplantation is potentially curative, due
      in large part to a graft-versus-myeloma (GVM) effect. Whereas patients who
      receive either allogeneic or autologous stem cell transplants for multiple
      myeloma have similar 3-5-year survival, only allograft recipients appear to enjoy
      long-term disease-free survival. High transplant-related mortality (TRM)
      associated with allogeneic stem cell transplantation is currently the major
      limitation to wider use of this potentially curative modality. This high
      mortality has been the major impetus for exploration of reduced intensity
      conditioning (RIC) regimens designed to allow engraftment of allogeneic stem
      cells. With follow-up now extending to 7 years, it is clear that when compared to
      myeloablative transplants, RIC allografts are associated with lower TRM; however,
      reduced mortality comes at a cost of higher rates of disease progression and
      relapse. Strategies designed to improve the therapeutic index of allografts
      include the use of more intensive, yet still non-myeloablative conditioning
      regimens, tandem autologous plus RIC allografts, peripheral blood cells rather
      than bone marrow, graft engineering to improve the GVM activity while reducing
      graft-versus-host disease, post-transplant maintenance and targeted conditioning
      therapies such as bone-seeking radioisotopes.

PMID- 16888616
TI  - Telomere length dynamics in normal hematopoiesis and in disease states
      characterized by increased stem cell turnover.
AB  - Telomeres both reflect and limit the replicative lifespan of normal somatic
      cells. Immature sub-populations of human CD34+38- hematopoietic stem cell (HSC)
      can be identified in vitro based on their growth kinetics and telomere length.
      Fluorescence in situ hybridization and flow cytometry (flow-FISH) has been used
      to characterize telomere length dynamics as a surrogate marker for HSC turnover
      in vivo. Investigations in normal steady-state hematopoiesis provided the basis
      for follow-up studies in model scenarios characterized by increased HSC turnover.
      Disorders with underlying malignant transformation of HSC (e.g., chronic myeloid
      leukemia (CML)) can be discriminated from disease states with increased HSC
      turnover rates secondary to depletion of the stem cell compartment, for example,
      as in defined bone marrow failure syndromes. In some of these model scenarios,
      the degree of telomere shortening can be correlated with disease duration,
      disease stage and severity as well as with response to disease-modifying
      treatment strategies. Whether increased telomere shortening represents a causal
      link between HSC turnover, replicative senescence and/or the induction of genetic
      instability in acquired HSC disorders remains to be shown. However, data from
      congenital disorders, like dyskeratosis congenita (DKC), suggest that disturbed
      telomere maintenance may play a role for replicative exhaustion of the HSC pool
      in vivo.

PMID- 16888618
TI  - Optimization of allogeneic transplant conditioning: not the time for dogma.
AB  - Numerous reduced-intensity conditioning regimens for allogeneic hematopoietic
      cell transplantation are currently being explored, primarily in older patients
      and in individuals with comorbid conditions who are not eligible for conventional
      myeloablative conditioning regimens. There is agreement that these approaches
      have reduced early transplant-related (non-relapse) toxicity and mortality. It is
      unclear, however, whether these strategies improve long-term survival.
      Furthermore, as most trials with reduced-intensity regimens have enrolled older
      patients and patients with comorbid conditions, it is not appropriate to compare
      the results of these trials to those obtained with more conventional approaches.
      It remains to be determined whether younger patients, and patients without
      comorbid conditions, will derive significant long-term benefits from reduced
      intensity regimens when compared to conventional strategies. It may be that the
      different approaches are complementary and in the end will preferentially serve
      specific patient populations based on age, comorbid conditions and malignancy
      type. To determine the role of reduced-intensity approaches, controlled
      prospective trials are needed, with enrolled patients being stratified according
      to comorbid conditions, disease characteristics, pre-transplant therapy and
      source of stem cells, at a minimum.

PMID- 16888619
TI  - Loss of antibodies and response to (re-)vaccination in children after treatment
      for acute lymphocytic leukemia: a systematic review.
AB  - Intensified chemotherapy regimens resulting in improved survival of children with
      acute lymphocytic leukemia (ALL) lead to concerns about therapy-induced immune
      damage reflected by the loss of protection of previous immunizations and the
      efficacy of (re-)vaccination. The severity of secondary immunodeficiency,
      however, is not clear and knowledge is based on a limited number of studies. We
      performed a systematic review on literature concerning vaccination data of
      children with ALL published since 1980. Eight studies fulfilled the inclusion
      criteria. Regarding antibody titers after treatment, the number of children who
      had preserved the defined protection level for antibodies differed widely,
      ranging from 17 to 98% for diphtheria, 27 to 82% for Bordetella pertussis, 20 to
      98% for tetanus, 62 to 100% for poliomyelitis, 35 to 100% for Haemophilus
      influenzae type B (HiB), 29 to 92% for mumps, 29 to 60% for measles and 72 to 92%
      for rubella. Most patients however responded to revaccination, demonstrating
      immunological recovery. Although the designs and results of the included studies
      varied widely, it can be concluded that cytostatic therapy for ALL in children
      results in a temporarily reduction of specific antibody levels. Memory is
      preserved but revaccination may be warranted. This is the first systematic review
      and the best possible current approximation of chemotherapy-induced immune damage
      in children after ALL treatment.

PMID- 16888620
TI  - CISK attenuates degradation of the chemokine receptor CXCR4 via the ubiquitin
      ligase AIP4.
AB  - HER2 overexpression in cancers causes hyperactivation of the PI 3-kinase pathway
      and elevated levels of the chemokine receptor CXCR4, which is strongly associated
      with increased metastatic potential. Here, we provide evidence that the cytokine
      independent survival kinase CISK is activated downstream of the PI 3-kinase
      dependent kinase PDK1 on endosomes and negatively regulates the lysosomal
      degradation of CXCR4. We demonstrate that CISK prevents CXCR4 degradation by
      inhibiting sorting of the receptor from early endosomes to lysosomes. In
      contrast, CISK does not interfere with ligand-induced degradation of epidermal
      growth factor receptors. CISK strongly interacts and colocalizes with the E3
      ubiquitin ligase AIP4, which is important for the ubiquitin-dependent lysosomal
      degradation of CXCR4. Moreover, the observed inhibition is both dependent on the
      interaction between CISK and AIP4 and on the activation status of CISK.
      Consistent with this, an activated form of CISK but not of the related kinase
      SGK1 phosphorylates specific sites of AIP4 in vitro. Taken together, these
      results reveal a critical function of CISK in specifically attenuating ubiquitin
      dependent degradation of CXCR4, and provide a mechanistic link between the PI 3
      kinase pathway and CXCR4 stability.

PMID- 16888621
TI  - Spo0A, the key transcriptional regulator for entrance into sporulation, is an
      inhibitor of DNA replication.
AB  - The transcription factor Spo0A is a master regulator for entry into sporulation
      in Bacillus subtilis and also regulates expression of the virulent B. subtilis
      phage phi29. Here, we describe a novel function for Spo0A, being an inhibitor of
      DNA replication of both, the phi29 genome and the B. subtilis chromosome. Binding
      of Spo0A near the phi29 DNA ends, constituting the two origins of replication of
      the linear phi29 genome, prevents formation of phi29 protein p6-nucleoprotein
      initiation complex resulting in inhibition of phi29 DNA replication. At the B.
      subtilis oriC, binding of Spo0A to specific sequences, which mostly coincide with
      DnaA-binding sites, prevents open complex formation. Thus, by binding to the
      origins of replication, Spo0A prevents the initiation step of DNA replication of
      either genome. The implications of this novel role of Spo0A for phage phi29
      development and the bacterial chromosome replication during the onset of
      sporulation are discussed.

PMID- 16888623
TI  - MUC1 oncoprotein blocks nuclear targeting of c-Abl in the apoptotic response to
      DNA damage.
AB  - The nonreceptor c-Abl tyrosine kinase binds to cytosolic 14-3-3 proteins and is
      targeted to the nucleus in the apoptotic response to DNA damage. The MUC1
      oncoprotein is overexpressed by most human carcinomas and blocks the induction of
      apoptosis by genotoxic agents. Using human carcinoma cells with gain and loss of
      MUC1 function, we show that nuclear targeting of c-Abl by DNA damage is abrogated
      by a MUC1-dependent mechanism. The results demonstrate that c-Abl phosphorylates
      MUC1 on Tyr-60 and forms a complex with MUC1 by binding of the c-Abl SH2 domain
      to the pTyr-60 site. Binding of MUC1 to c-Abl attenuates phosphorylation of c-Abl
      on Thr-735 and the interaction between c-Abl and cytosolic 14-3-3. We also show
      that expression of MUC1 with a mutation at Tyr-60 (i) disrupts the interaction
      between MUC1 and c-Abl, (ii) relieves the MUC1-induced block of c-Abl
      phosphorylation on Thr-735 and binding to 14-3-3, and (iii) attenuates the MUC1
      antiapoptotic function. These findings indicate that MUC1 sequesters c-Abl in the
      cytoplasm and thereby inhibits apoptosis in the response to genotoxic anticancer
      agents.

PMID- 16888622
TI  - SAGA binds TBP via its Spt8 subunit in competition with DNA: implications for TBP
      recruitment.
AB  - In yeast, the multisubunit SAGA (Spt-Ada-Gcn5-acetyltransferase) complex acts as
      a coactivator to recruit the TATA-binding protein (TBP) to the TATA box, a
      critical step in eukaryotic gene regulation. However, it is unclear which SAGA
      subunits are responsible for SAGA's direct interactions with TBP and precisely
      how SAGA recruits TBP to the promoter. We have used chemical crosslinking to
      identify Spt8 and Ada1 as potential SAGA subunits that interact with TBP, and we
      find that both Spt8 and SAGA bind directly to TBP monomer in competition with TBP
      dimer. We further find that Spt8 and SAGA compete with DNA to bind TBP rather
      than forming a triple complex. Our results suggest a handoff model for SAGA
      recruitment of TBP: instead of binding together with TBP at the TATA box,
      activator-recruited SAGA transfers TBP to the TATA box. This simple model can
      explain SAGA's observed ability to both activate and repress transcription.

PMID- 16888624
TI  - TOR regulates late steps of ribosome maturation in the nucleoplasm via Nog1 in
      response to nutrients.
AB  - The protein kinase TOR (target of rapamycin) controls several steps of ribosome
      biogenesis, including gene expression of rRNA and ribosomal proteins, and
      processing of the 35S rRNA precursor, in the budding yeast Saccharomyces
      cerevisiae. Here we show that TOR also regulates late stages of ribosome
      maturation in the nucleoplasm via the nuclear GTP-binding protein Nog1. Nog1
      formed a complex that included 60S ribosomal proteins and pre-ribosomal proteins
      Nop7 and Rlp24. The Nog1 complex shuttled between the nucleolus and the
      nucleoplasm for ribosome biogenesis, but it was tethered to the nucleolus by both
      nutrient depletion and TOR inactivation, causing cessation of the late stages of
      ribosome biogenesis. Furthermore, after this, Nog1 and Nop7 proteins were lost,
      leading to complete cessation of ribosome maturation. Thus, the Nog1 complex is a
      critical regulator of ribosome biogenesis mediated by TOR. This is the first
      description of a physiological regulation of nucleolus-to-nucleoplasm
      translocation of pre-ribosome complexes.

PMID- 16888625
TI  - RNA polymerase and an activator form discrete subcomplexes in a transcription
      initiation complex.
AB  - Using high-resolution atomic force microscopy (AFM) we show that in a ternary
      complex of an activator protein, FIS, and RNA polymerase containing the sigma(70)
      specificity factor at the Escherichia coli tyrT promoter the polymerase and the
      activator form discrete, but connected, subcomplexes in close proximity. This is
      the first time that a ternary complex between an activator, a sigma(70)
      polymerase holoenzyme and promoter DNA has been visualised. Individually FIS and
      RNA polymerase wrap approximately 80 and 150 bp of promoter DNA, respectively. We
      suggest that the architecture of the ternary complex provides a general paradigm
      for the facilitation of direct, but weak, interactions between polymerase and an
      activator.

PMID- 16888626
TI  - Mutation in the U2 snRNA influences exon interactions of U5 snRNA loop 1 during
      pre-mRNA splicing.
AB  - The U2 and U6 snRNAs contribute to the catalysis of intron removal while U5 snRNA
      loop 1 holds the exons for ligation during pre-mRNA splicing. It is unclear how
      different exons are positioned precisely with U5 loop 1. Here, we investigate the
      role of U2 and U6 in positioning the exons with U5 loop 1. Reconstitution in
      vitro of spliceosomes with mutations in U2 allows U5-pre-mRNA interactions before
      the first step of splicing. However, insertion in U2 helix Ia disrupts U5-exon
      interactions with the intron lariat-3' exon splicing intermediate. Conversely, U6
      helix Ia insertions prevent U5-pre-mRNA interactions before the first step of
      splicing. In vivo, synthetic lethal interactions have been identified between U2
      insertion and U5 loop 1 insertion mutants. Additionally, analysis of U2 insertion
      mutants in vivo reveals that they influence the efficiency, but not the accuracy
      of splicing. Our data suggest that U2 aligns the exons with U5 loop 1 for
      ligation during the second step of pre-mRNA splicing.

PMID- 16888627
TI  - Nud1p, the yeast homolog of Centriolin, regulates spindle pole body inheritance
      in meiosis.
AB  - Nud1p, a protein homologous to the mammalian centrosome and midbody component
      Centriolin, is a component of the budding yeast spindle pole body (SPB), with
      roles in anchorage of microtubules and regulation of the mitotic exit network
      during vegetative growth. Here we analyze the function of Nud1p during yeast
      meiosis. We find that a nud1-2 temperature-sensitive mutant has two meiosis
      related defects that reflect genetically distinct functions of Nud1p. First, the
      mutation affects spore formation due to its late function during spore
      maturation. Second, and most important, the mutant loses its ability to
      distinguish between the ages of the four spindle pole bodies, which normally
      determine which SPB would be preferentially included in the mature spores. This
      affects the regulation of genome inheritance in starved meiotic cells and leads
      to the formation of random dyads instead of non-sister dyads under these
      conditions. Both functions of Nud1p are connected to the ability of Spc72p to
      bind to the outer plaque and half-bridge (via Kar1p) of the SPB.

PMID- 16888628
TI  - Genome-wide replication profiles of S-phase checkpoint mutants reveal fragile
      sites in yeast.
AB  - The S-phase checkpoint kinases Mec1 and Rad53 in the budding yeast, Saccharomyces
      cerevisiae, are activated in response to replication stress that induces
      replication fork arrest. In the absence of a functional S-phase checkpoint,
      stalled replication forks collapse and give rise to chromosome breakage. In an
      attempt to better understand replication dynamics in S-phase checkpoint mutants,
      we developed a replication origin array for budding yeast that contains 424 of
      432 previously identified potential origin regions. As expected, mec1-1 and rad53
      1 mutants failed to inhibit late origin activation. Surprisingly however, 17
      early-firing regions were not replicated efficiently in these mutants. This was
      not due to a lack of initiation, but rather to problems during elongation, as
      replication forks arrested in close proximity to these origins, resulting in the
      accumulation of small replication intermediates and eventual replication fork
      collapse. Importantly, these regions were not only prone to chromosome breakage
      in the presence of exogenous stress but also in its absence, similar to fragile
      sites in the human genome.

PMID- 16888631
TI  - Congenital melanocytic nevi frequently harbor NRAS mutations but no BRAF
      mutations.
AB  - Most melanocytic nevi develop on sun-exposed skin during childhood and
      adolescence and commonly harbor BRAF mutations or, less frequently, NRAS
      mutations. A small subset of nevi is present at birth, and therefore must develop
      independently of UV light. To assess whether these nevi have a different mutation
      spectrum than those that develop on sun-exposed skin, we determined the BRAF and
      NRAS mutation frequencies in 32 truly congenital nevi. We found no BRAF
      mutations, but 81% (26/32) harbored mutations in NRAS. Consistently, seven of 10
      (70%) proliferating nodules that developed early in life in congenital nevi
      showed mutations in NRAS. A separate set of nevi that displayed histological
      features frequently found in nevi present at birth ("congenital pattern nevi")
      but lacked a definitive history of presence at birth showed an inverse mutation
      pattern with common BRAF mutations (20/28 or 71%) and less frequent NRAS
      mutations (7/28 or 25%). Thus, nevi that develop in utero are genetically
      distinct from those that develop later, and histopathologic criteria alone are
      unable to reliably distinguish the two groups. The results are consistent with
      the finding in melanoma that BRAF mutations are uncommon in neoplasms that
      develop in the absence of sun-exposure.

PMID- 16888630
TI  - Structure of the monomeric outer-membrane porin OmpG in the open and closed
      conformation.
AB  - OmpG, a monomeric pore-forming protein from Escherichia coli outer membranes, was
      refolded from inclusion bodies and crystallized in two different conformations.
      The OmpG channel is a 14-stranded beta-barrel, with short periplasmic turns and
      seven extracellular loops. Crystals grown at neutral pH show the channel in the
      open state at 2.3 A resolution. In the 2.7 A structure of crystals grown at pH
      5.6, the pore is blocked by loop 6, which folds across the channel. The
      rearrangement of loop 6 appears to be triggered by a pair of histidine residues,
      which repel one another at acidic pH, resulting in the breakage of neighbouring H
      bonds and a lengthening of loop 6 from 10 to 17 residues. A total of 151 ordered
      LDAO detergent molecules were found in the 2.3 A structure, mostly on the
      hydrophobic outer surface of OmpG, mimicking the outer membrane lipid bilayer,
      with three LDAO molecules in the open pore. In the 2.7 A structure, OmpG binds
      one OG and one glucose molecule as sugar substrates in the closed pore.

PMID- 16888632
TI  - Novel anti-inflammatory properties of the angiogenesis inhibitor vasostatin.
AB  - Endothelial cells are critically involved in the pathogenesis of inflammation,
      which is characterized by vasopermeability, plasma leakage, leukocyte
      recruitment, and neovascularization. Therefore, inhibitors of endothelial cell
      function could reduce inflammation. In this study, we evaluated the effects of
      the angiogenesis inhibitor vasostatin on inflammations induced by contact
      hypersensitivity reactions in mouse ears. Vasostatin-treated mice revealed
      significantly reduced edema formation, resulting from lower plasma leakage and
      inhibition of inflammation-associated vascular remodeling. Intravital microscopy
      studies of inflamed ears showed a decrease in the fraction of rolling leukocytes
      in vasostatin-treated mice, and Lycopersicon esculentum lectin-perfused ears
      revealed fewer leukocytes adherent to the vessel wall. The inflammatory
      infiltrate from vasostatin-treated mice was characterized by fewer CD8+ T cells,
      neutrophils, and macrophages compared to the saline-treated animals. In a
      modified Miles assay, vasostatin inhibited vascular endothelial growth factor-A
      induced permeability, and inflamed ear tissues from vasostatin-treated mice
      expressed significantly reduced levels of the vascular destabilizer angiopoietin
      2. These results reveal a previously unrecognized anti-inflammatory property of
      the angiogenesis inhibitor vasostatin, and suggest that vasostatin is a potential
      candidate drug for the treatment of inflammation.

PMID- 16888629
TI  - Structure of the Keap1:Nrf2 interface provides mechanistic insight into Nrf2
      signaling.
AB  - Keap1 is a BTB-Kelch substrate adaptor protein that regulates steady-state levels
      of Nrf2, a bZIP transcription factor, in response to oxidative stress. We have
      determined the structure of the Kelch domain of Keap1 bound to a 16-mer peptide
      from Nrf2 containing a highly conserved DxETGE motif. The Nrf2 peptide contains
      two short antiparallel beta-strands connected by two overlapping type I beta
      turns stabilized by the aspartate and threonine residues. The beta-turn region
      fits into a binding pocket on the top face of the Kelch domain and the glutamate
      residues form multiple hydrogen bonds with highly conserved residues in Keap1.
      Mutagenesis experiments confirmed the role of individual amino acids for binding
      of Nrf2 to Keap1 and for Keap1-mediated repression of Nrf2-dependent gene
      expression. Our results provide a detailed picture of how a BTB-Kelch substrate
      adaptor protein binds to its cognate substrate and will enable the rational
      design of novel chemopreventive agents.

PMID- 16888633
TI  - Expression profiling of UVB response in melanocytes identifies a set of p53
      target genes.
AB  - Epidermal melanocytes execute specific physiological programs in response to UV
      radiation (UVR) at the cutaneous interface. Many melanocytic responses, including
      increased dendrite formation, enhanced melanogenesis/melanization, and cell cycle
      arrest impact the ability of melanocytes to survive and to attenuate the UVR
      insult. Although some of the molecules that underlie these UVR programs are
      known, a coherent view of UVR-induced transcriptional changes is lacking. Using
      primary melanocyte cultures, we assessed for UVR-mediated alterations in over
      47,000 transcripts using Affymetrix Human Genome U133 Plus 2.0 microarrays. From
      the 100 most statistically robust changes in transcript level, there were 84
      genes that were suppressed >2.0-fold by UVR; among these transcripts, the
      identities of 48 of these genes were known. Similarly, there were 99 genes that
      were induced >2.0-fold by UVR; the identity of 57 of these genes were known. We
      then subjected these top 100 changes to the Ingenuity Pathway analysis program
      and identified a group of p53 targets including the cell cycle regulator CDKN1A
      (p21CIP), the WNT pathway regulator DKK1 (dickkopf homolog 1), the receptor
      tyrosine kinase EPHA2, growth factor GDF15, ferrodoxin reductase (FDXR), p53
      inducible protein TP53I3, transcription factor ATF3, DNA repair enzyme DDB2, and
      the beta-adrenergic receptor ADBR2. These genes were also found to be
      consistently elevated by UVR in six independent melanocyte lines, although there
      were interindividual variations in magnitude. WWOX, whose protein product
      interacts and regulates p53 and p73, was found to be consistently suppressed by
      UVR. There was also a subgroup of neurite/axonal developmental genes that were
      altered in response to UVR, suggesting that melanocytic and neuronal arborization
      may share similar mechanisms. When compared to melanomas, the basal levels of
      many of these p53-responsive genes were greatly dysregulated. Three genes-
      CDKN1A, DDB2 and ADRB2--exhibited a trend towards loss of expression in melanomas
      thereby raising the possibility of a linked role in tumorigenesis. These
      expression data provide a global view of UVR-induced changes in melanocytes and,
      more importantly, generate novel hypotheses regarding melanocyte physiology.

PMID- 16888637
TI  - The presentation of data relating to visual acuity.

PMID- 16888636
TI  - Intravitreal triamcinolone staining observation of residual undetached cortical
      vitreous after posterior vitreous detachment.

PMID- 16888639
TI  - The prevalence of low vision and blindness in an inner city in Canada.

PMID- 16888640
TI  - Performance of GDx VCC in eyes with peripapillary atrophy: comparison of three
      circle sizes.
AB  - PURPOSE: A scanning laser polarimetry (GDx VCC) equips three different sized
      measurement circles. In eyes with peripapillary atrophy (PPA), the GDx
      measurement becomes inaccurate when the circle falls on PPA. The aim of this
      study was to evaluate performance of the three circles of GDx measurement in eyes
      with PPA. METHODS: Three different sized circles were compared regarding
      frequency of PPA, which fell on each circle in 282 open-angle glaucoma (OAG)
      eyes, reproducibility of GDx parameters in 24 normal and 22 OAG eyes, and ability
      to detect glaucoma in 50 normal and 50 OAG eyes. RESULTS: PPA was observed in 230
      (82%) of 282 OAG eyes. PPA fell on the small circle (default setting), medium,
      and large circles in 119 (43%), 38 (14%), and 12 (4%) of the 280 OAG eyes.
      Reproducibility of GDx parameters was not significantly different among three
      circles in normal eyes (P>0.05), whereas coefficients of reproducibility of TSNIT
      average (P=0.006) and superior average (P=0.035) were smaller in the smaller
      circles in OAG eyes. GDx parameters significantly correlated (P<0.001), but were
      significantly different (P<0.05) between the small and medium circles. The area
      under receiver operating characteristic curves for dividing OAG from normal eyes
      using GDx parameters was similar between the small and medium circles.
      CONCLUSIONS: If the medium circles were used, obstructing influences of PPA on
      GDx measurement could be avoided more often in Japanese OAG eyes with similar
      reproducibility and comparable ability to detect glaucoma compared to those with
      the default small circle.

PMID- 16888641
TI  - Cellular retention on diagnostic contact lenses: an evaluation of current
      cleaning protocol.
AB  - AIMS: To compare cellular contamination of diagnostic contact lenses after two
      different cleaning methods. METHODS: Twenty-five used diagnostic contact lenses
      were cleaned by two different methods and the material retained on their contact
      surface examined for cells. Two diagnostic contact lenses were examined using
      electron microscopy and surface debris was subjected to x-ray photoelectron
      spectroscopy. RESULTS: Significantly more cells were present on used lenses
      compared with controls (P<0.001). There was no significant difference in total
      cell count between the lenses subjected to the two cleaning strategies but the
      lenses simply wiped clean retained marginally more nucleated cells than controls
      (P=0.039). Electron microscopy showed the majority of the debris on or close to
      the rim of the lens. X-ray photoelectron spectroscopy confirmed the presence of
      proteinaceous material. CONCLUSIONS: Regardless of cleaning method, significant
      cellular debris is retained on the surface of diagnostic contact lenses after
      use.

PMID- 16888642
TI  - Optical coherence tomography, frequency-doubling technology, and colour Doppler
      imaging in ocular hypertension.
AB  - PURPOSE: To study in ocular hypertension (OH) the retinal nerve fibre layer
      (RNFL) with optical coherence tomography (OCT) and the neuronal function with
      frequency-doubling technology (FDT) to assess which of the two methods was more
      sensitive in detecting early glaucomatous damage. Furthermore, a colour Doppler
      imaging (CDI) of the optic nerve was carried out to highlight any correlation
      with RNFL thickness and FDT abnormality. MATERIALS AND METHODS: We enrolled 28
      ocular hypertensive patients who underwent OCT of the RNFL and FDT. Moreover, we
      performed a CDI of the ophthalmic artery (OA), central retinal artery (CRA), and
      posterior ciliary arteries (PCAs). RESULTS: The patients with OH following OCT
      revealed a significant thinning in the RNFL as compared to the control group only
      in the inferior quadrant: 122.250+/-14.091 vs131.750+/-10.729 mum (P<0.045). As
      regards FDT, there was a significant difference between the two groups only for
      pattern standard deviation (PSD): 3.873+/-1.488 vs1.938+/-0.704 dB (P<0.044). In
      OH and in the control group, CDI resistance index (RI) in the OA was 0.768+/
      0.012 vs0.745+/-0.019 (P<0.022), in the CRA was 0.66+/-0.012 vs0.645+/-0.019
      (P<0.032), and in PCAs was 0.673+/-0.039 vs0.622+/-0.012 (P<0.037). The OCT had a
      sensitivity of 83% but only in the inferior RNFL quadrant. The FDT-PSD revealed a
      sensitivity of 85%. CONCLUSIONS: Both FDT and OCT detect early glaucomatous
      damage with a slightly superior sensitivity of FDT vsOCT. The CDI measurements
      suggest that circulatory abnormalities may have a role in the development of OCT
      and FDT damage.

PMID- 16888643
TI  - Cardiolipin deficiency releases cytochrome c from the inner mitochondrial
      membrane and accelerates stimuli-elicited apoptosis.
AB  - Cardiolipin (CL) is a mitochondria-specific phospholipid synthesized by CL
      synthase (CLS). We describe here a human gene for CLS and its analysis via RNAi
      knockdown on apoptotic progression. Although mitochondrial membrane potential is
      unchanged in cells containing only 25% of the normal amount of CL, free
      cytochrome c (cyt. c) is detected in the intermembrane space and the mitochondria
      exhibit signs of reorganized cristae. However, the release of cyt. c from the
      mitochondria still requires apoptotic stimulation. Increased sensitivity to
      apoptotic signals and accelerated rates of apoptosis are observed in CL-deficient
      cells, followed by elevated levels of secondary necrosis. Apoptosis is thought to
      progress via binding of truncated Bid (tBid) to mitochondrial CL, followed by CL
      oxidation which results in cyt. c release. The exaggerated and accelerated
      apoptosis observed in CL-deficient cells is matched by an accelerated reduction
      in membrane potential and increased cyt. c release, but not by decreased tBid
      binding. This study suggests that the CL/cyt. c relationship is important in
      apoptotic progression and that regulating CL oxidation or/and deacylation could
      represent a possible therapeutic target.

PMID- 16888644
TI  - Targeted Vpr-derived peptides reach mitochondria to induce apoptosis of
      alphaVbeta3-expressing endothelial cells.
AB  - The HIV-1 encoded apoptogenic protein Vpr induces mitochondrial membrane
      permeabilization (MMP) via interactions with the voltage-dependent anion channel
      (VDAC) and the adenine nucleotide translocator (ANT). We have designed a peptide,
      TEAM-VP, composed of two functional domains, one a tumor blood vessel RGD-like
      'homing' motif and the other an MMP-inducing sequence derived from Vpr. When
      added to isolated mitochondria, TEAM-VP interacts with ANT and VDAC, reduces
      oxygen consumption and overcomes Bcl-2 protection to cause inner and outer MMP.
      TEAM-VP specifically recognizes cell-surface expressed alpha(V)beta(3) integrins,
      internalizes, temporarily localizes to lysosomes and progressively co-distributes
      with the mitochondrial compartment with no sign of lysosomal membrane
      permeabilization. Finally TEAM-VP reaches mitochondria of angiogenic endothelial
      cells to induce mitochondrial fission, dissipation of the mitochondrial
      transmembrane potential (DeltaPsi(m)), cytochrome c release and apoptosis
      hallmarks. Hence, this chimeric peptide constitutes the first example of a virus
      derived mitochondriotoxic compound as a candidate to kill selectively tumor neo
      endothelia.

PMID- 16888645
TI  - FKHRL1-mediated expression of Noxa and Bim induces apoptosis via the mitochondria
      in neuroblastoma cells.
AB  - Protein kinase-B (PKB) and its target, the forkhead transcription factor like 1
      (FKHRL1)/FoxO3a, have been suggested as regulators of neurotrophin-mediated cell
      survival in neuronal cells. We analyzed human neuroblastoma cells and found that
      FKHRL1 was phosphorylated, suggesting its inactivation. To study FKHRL1 function,
      we infected SH-EP and NB15 cells with a 4OH-tamoxifen-regulated FKHRL1(A3)ER(tm)
      transgene. Activation of FKHRL1 promoted cytochrome-c release and caspase
      dependent apoptosis. FKHRL1 induced TRAIL and the BH3-only proteins Noxa and Bim,
      implicating both extrinsic and intrinsic death pathways. However, expression of
      dnFADD did not inhibit FKHRL1-induced cell death, whereas Bcl2 protected against
      apoptosis. This excluded the death-receptor pathway and suggested that cell death
      decision is regulated by Bcl2-rheostat. Importantly, RNAi knockdown of Noxa or
      Bim decreased apoptosis, indicating that Noxa and Bim cooperate to mediate FKHRL1
      induced cell death. We conclude that Noxa and Bim establish a connection between
      FKHRL1 and mitochondria, and that both BH3-only proteins are critically involved
      in FKHRL1-induced apoptosis in neuroblastoma.

PMID- 16888646
TI  - Functional characterization of the Bcl-2 gene family in the zebrafish.
AB  - Members of the Bcl-2 protein family control the intrinsic apoptosis pathway. To
      evaluate the importance of this family in vertebrate development, we investigated
      it in the zebrafish (Danio rerio). We found that the zebrafish genome encodes
      structural and functional homologs of most mammalian Bcl-2 family members,
      including multi-Bcl-2-homology (BH) domain proteins and BH3-only proteins.
      Apoptosis induction by gamma-irradiation required zBax1 and zPuma, and could be
      prevented by overexpression of homologs of prosurvival Bcl-2 family members.
      Surprisingly, zebrafish Bax2 (zBax2) was homologous to mammalian Bax by sequence
      and synteny, yet demonstrated functional conservation with human Bak. Morpholino
      knockdown of both zMcl-1a and zMcl-1b revealed their critical role in early
      embryonic zebrafish development, and in the modulation of apoptosis activation
      through the extrinsic pathway. These data indicate substantial functional
      similarity between zebrafish and mammalian Bcl-2 family members, and establish
      the zebrafish as a relevant model for studying the intrinsic apoptosis pathway.

PMID- 16888647
TI  - Delineation of the cell-extrinsic apoptosis pathway in the zebrafish.
AB  - The mammalian extrinsic apoptosis pathway is triggered by Fas ligand (FasL) and
      Apo2 ligand/tumor necrosis factor (TNF)-related apoptosis-inducing ligand
      (Apo2L/TRAIL). Ligand binding to cognate receptors activates initiator caspases
      directly in a death-inducing signaling complex. In Drosophila, TNF ligand binding
      activates initiator caspases indirectly, through JNK. We characterized the
      extrinsic pathway in zebrafish to determine how it operates in a nonmammalian
      vertebrate. We identified homologs of FasL and Apo2L/TRAIL, their receptors, and
      other components of the cell death machinery. Studies with three Apo2L/TRAIL
      homologs demonstrated that they bind the receptors zHDR (previously linked to
      hematopoiesis) and ovarian TNFR (zOTR). Ectopic expression of these ligands
      during embryogenesis induced apoptosis in erythroblasts and notochord cells.
      Inhibition of zHDR, zOTR, the adaptor zFADD, or caspase-8-like proteases blocked
      ligand-induced apoptosis, as did antiapoptotic Bcl-2 family members. Thus, the
      extrinsic apoptosis pathway in zebrafish closely resembles its mammalian
      counterpart and cooperates with the intrinsic pathway to trigger tissue-specific
      apoptosis during embryogenesis in response to ectopic Apo2L/TRAIL expression.

PMID- 16888648
TI  - Altered gene expression in cells from patients with lysosomal storage disorders
      suggests impairment of the ubiquitin pathway.
AB  - By comparing mRNA profiles in cultured fibroblasts from patients affected with
      lysosomal storage diseases, we identified differentially expressed genes common
      to these conditions. These studies, confirmed by biochemical experiments,
      demonstrated that lysosomal storage is associated with downregulation of
      ubiquitin C-terminal hydrolase, UCH-L1 in the cells of eight different lysosomal
      disorders, as well as in the brain of a mouse model of Sandhoff disease.
      Induction of lysosomal storage by the cysteine protease inhibitor E-64 also
      reduced UCH-L1 mRNA, protein level and activity. All cells exhibiting lysosomal
      storage contained ubiquitinated protein aggregates and showed reduced levels of
      free ubiquitin and decreased proteasome activity. The caspase-mediated apoptosis
      in E-64-treated fibroblasts was reversed by transfection with a UCH-L1 plasmid,
      and increased after downregulation of UCH-L1 by siRNA, suggesting that UCH-L1
      deficiency and impairment of the ubiquitin-dependent protein degradation pathway
      can contribute to the increased cell death observed in many lysosomal storage
      disorders.

PMID- 16888649
TI  - RAD18-independent ubiquitination of proliferating-cell nuclear antigen in the
      avian cell line DT40.
AB  - Ubiquitination of proliferating-cell nuclear antigen (PCNA) at K164 by RAD6/RAD18
      has a key role in DNA damage tolerance in yeast. Here, we report on the first
      genetic study of this modification in a vertebrate cell. As in yeast, mutation of
      K164 of PCNA to arginine in the avian cell line DT40 results in sensitivity to
      DNA damage but, by contrast, the DT40 pcnaK164R mutant is more sensitive than the
      rad18 mutant. Consistent with this, we show the presence of residual
      ubiquitination of PCNA at K164 in the absence of functional RAD18, suggesting the
      presence of an alternate PCNA ubiquitinating enzyme in DT40. Furthermore, RAD18
      and PCNA K164 have non-overlapping roles in the suppression of sister chromatid
      exchange in DT40, showing that RAD18 has other functions that do not involve the
      ubiquitination of PCNA.

PMID- 16888650
TI  - Glucocorticoids cause rapid dissociation of a T-cell-receptor-associated protein
      complex containing LCK and FYN.
AB  - Although glucocorticoid (GC)-induced nongenomic effects have been reported, the
      underlying mechanisms remain unexplained. We previously described that lymphocyte
      specific protein tyrosine kinase (LCK) and FYN oncogene related to SRC, FGR, YES
      (FYN) mediate GC-induced inhibition of T-cell-receptor (TCR) signalling. Here we
      characterize the underlying molecular mechanism. The present study shows that the
      GC receptor is part of a TCR-linked multiprotein complex containing heat-shock
      protein (HSP)90, LCK and FYN, which is essential for TCR-dependent LCK/FYN
      activation. Experiments with cells transfected with GC-receptor short interfering
      RNA (siRNA) showed that the GC receptor is an essential component of the TCR
      signalling complex. Short-term GC treatment induces dissociation of this protein
      complex, resulting in impaired TCR signalling as a consequence of abrogated
      LCK/FYN activation. HSP90siRNA-transfected cells are not able to assemble this
      TCR-associated multiprotein complex, and accordingly HSP90siRNA treatment mimics
      GC effects on LCK/FYN activities. These observations support a model for
      nongenomic GC-induced immunosuppression on the basis of dissolution of membrane
      bound GC-receptor multiprotein complexes after GC-receptor ligation.

PMID- 16888651
TI  - Double-strand breaks arising by replication through a nick are repaired by
      cohesin-dependent sister-chromatid exchange.
AB  - Molecular studies on double-strand break (DSB) repair in mitosis are usually
      performed with enzymatically induced DSBs, but spontaneous DSBs might arise
      because of replication failures, for example when replication encounters nicks.
      To study repair of replication-born DSBs, we defined a system in Saccharomyces
      cerevisiae for the induction of a site-specific single-strand break. We show that
      a 21-base pair (bp) HO site is cleaved at only one strand by the HO endonuclease,
      with the resulting nick being converted into a DSB by replication during the S
      phase. Repair of such replication-born DSBs occurs by sister-chromatid exchange
      (SCE). We provide molecular evidence that cohesins are required for repair of
      replication-born DSBs by SCE, as determined in smc3, scc1 and scc2 mutants, but
      not for other recombinational repair events. This work opens new perspectives to
      understand the importance of single-strand breaks as a source of recombination
      and the relevance of cohesion in the repair of replication-born DSBs.

PMID- 16888653
TI  - High-spin [Fe(TTP)(THF)(2)].

PMID- 16888652
TI  - Drug-target residence time and its implications for lead optimization.
AB  - Much of drug discovery today is predicated on the concept of selective targeting
      of particular bioactive macromolecules by low-molecular-mass drugs. The binding
      of drugs to their macromolecular targets is therefore seen as paramount for
      pharmacological activity. In vitro assessment of drug-target interactions is
      classically quantified in terms of binding parameters such as IC(50) or K(d).
      This article presents an alternative perspective on drug optimization in terms of
      drug-target binary complex residence time, as quantified by the dissociative half
      life of the drug-target binary complex. We describe the potential advantages of
      long residence time in terms of duration of pharmacological effect and target
      selectivity.

PMID- 16888655
TI  - A management case study: challenges of initiating an information service in
      molecular biology and genetics.

PMID- 16888656
TI  - Jean Pugh Shipman AHIP, Medical Library Association President 2006-2007.

PMID- 16888657
TI  - Open access: implications for scholarly publishing and medical libraries.
AB  - PURPOSE: The paper reviews and analyzes the evolution of the open access (OA)
      publishing movement and its impact on the traditional scholarly publishing model.
      PROCEDURES: A literature survey and analysis of definitions of OA, problems with
      the current publishing model, historical developments, funding agency responses,
      stakeholder viewpoints, and implications for scientific libraries and publishing
      are performed. FINDINGS: The Internet's transformation of information access has
      fueled interest in reshaping what many see as a dysfunctional, high-cost system
      of scholarly publishing. For years, librarians alone advocated for change, until
      relatively recently when interest in OA and related initiatives spread to the
      scientific community, governmental groups, funding agencies, publishers, and the
      general public. CONCLUSIONS: Most stakeholders acknowledge that change in the
      publishing landscape is inevitable, but heated debate continues over what form
      this transformation will take. The most frequently discussed remedies for the
      troubled current system are the "green" road (self-archiving articles published
      in non-OA journals) and the "gold" road (publishing in OA journals). Both
      movements will likely intensify, with a multiplicity of models and initiatives
      coexisting for some time.

PMID- 16888658
TI  - Medicus Deus: a review of factors affecting hospital library services to patients
      between 1790-1950.
AB  - QUESTION: What are some of the historical societal, medical, and public health
      trends leading to today's provision of hospital library services to patients?
      DATA SOURCES: Literature from the archives of the Bulletin of the Medical Library
      Association and other library sources, medical journals, primary historical
      documents, and texts from the history of medicine form the core of this review.
      STUDY SELECTION: The period of review extends from about 1790 through 1950 and
      focuses solely on trends in the United States. Of primary concern are explicitly
      documented examples that appear to illustrate the patient-physician relationship
      and those between librarians and their patient-patrons during the earliest years
      of the profession's development. DATA EXTRACTION: An historical timeline was
      created to allow the identification of major trends that may have affected
      library services. Multiple literature searches were conducted using library,
      medical, and health anthropology resources. When possible, primary sources were
      preferred over reviews. MAIN RESULTS: Juxtapositioning historical events allows
      the reader to obtain an overview of the roots of consumer health services in
      medical libraries and to consider their potential legacy in today's health care
      libraries. CONCLUSION: This review article highlights early developments in
      hospital library service to patients. Further research is needed to verify a
      preliminary conclusion that in some medical library settings, services to the
      general public are shaped by the broader health care environment as it has
      evolved.

PMID- 16888659
TI  - Team effectiveness in academic medical libraries: a multiple case study.
AB  - OBJECTIVES: The objective of this study is to apply J. Richard Hackman's
      framework on team effectiveness to academic medical library settings. METHODS:
      The study uses a qualitative, multiple case study design, employing interviews
      and focus groups to examine team effectiveness in three academic medical
      libraries. Another site was selected as a pilot to validate the research design,
      field procedures, and methods to be used with the cases. In all, three interviews
      and twelve focus groups, with approximately seventy-five participants, were
      conducted at the case study libraries. FINDINGS: Hackman identified five
      conditions leading to team effectiveness and three outcomes dimensions that
      defined effectiveness. The participants in this study identified additional
      characteristics of effectiveness that focused on enhanced communication,
      leadership personality and behavior, and relationship building. The study also
      revealed an additional outcome dimension related to the evolution of teams.
      CONCLUSIONS: Introducing teams into an organization is not a trivial matter.
      Hackman's model of effectiveness has implications for designing successful
      library teams.

PMID- 16888660
TI  - The National Institutes of Health (NIH) Policy on Enhancing Public Access:
      tracking institutional contribution rates.

PMID- 16888662
TI  - Broad issues to consider for library involvement in bioinformatics.
AB  - BACKGROUND: The information landscape in biological and medical research has
      grown far beyond literature to include a wide variety of databases generated by
      research fields such as molecular biology and genomics. The traditional role of
      libraries to collect, organize, and provide access to information can expand
      naturally to encompass these new data domains. METHODS: This paper discusses the
      current and potential role of libraries in bioinformatics using empirical
      evidence and experience from eleven years of work in user services at the
      National Center for Biotechnology Information. FINDINGS: Medical and science
      libraries over the last decade have begun to establish educational and support
      programs to address the challenges users face in the effective and efficient use
      of a plethora of molecular biology databases and retrieval and analysis tools. As
      more libraries begin to establish a role in this area, the issues they face
      include assessment of user needs and skills, identification of existing services,
      development of plans for new services, recruitment and training of specialized
      staff, and establishment of collaborations with bioinformatics centers at their
      institutions. CONCLUSIONS: Increasing library involvement in bioinformatics can
      help address information needs of a broad range of students, researchers, and
      clinicians and ultimately help realize the power of bioinformatics resources in
      making new biological discoveries.

PMID- 16888663
TI  - A Web-based assessment of bioinformatics end-user support services at US
      universities.
AB  - OBJECTIVES: This study was conducted to gauge the availability of bioinformatics
      end-user support services at US universities and to identify the providers of
      those services. The study primarily focused on the availability of short-term
      workshops that introduce users to molecular biology databases and analysis
      software. METHODS: Websites of selected US universities were reviewed to
      determine if bioinformatics educational workshops were offered, and, if so, what
      organizational units in the universities provided them. RESULTS: Of 239 reviewed
      universities, 72 (30%) offered bioinformatics educational workshops. These
      workshops were located at libraries (N = 15), bioinformatics centers (N = 38), or
      other facilities (N = 35). No such training was noted on the sites of 167
      universities (70%). Of the 115 bioinformatics centers identified, two-thirds did
      not offer workshops. CONCLUSIONS: This analysis of university Websites indicates
      that a gap may exist in the availability of workshops and related training to
      assist researchers in the use of bioinformatics resources, representing a
      potential opportunity for libraries and other facilities to provide training and
      assistance for this growing user group.

PMID- 16888664
TI  - Vignettes: Diverse library staff offering diverse bioinformatics services.
AB  - OBJECTIVES: The paper gives examples of the bioinformatics services provided in a
      variety of different libraries by librarians with a broad range of educational
      background and training. METHODS: Two investigators sent an email inquiry to
      attendees of the "National Center for Biotechnology Information's (NCBI)
      Introduction to Molecular Biology Information Resources" or "NCBI Advanced
      Workshop for Bioinformatics Information Specialists (NAWBIS)" courses. The thirty
      five-item questionnaire addressed areas such as educational background, library
      setting, types and numbers of users served, and bioinformatics training and
      support services provided. Answers were compiled into program vignettes.
      DISCUSSION: The bioinformatics support services addressed in the paper are based
      in libraries with academic and clinical settings. Services have been established
      through different means: in collaboration with biology faculty as part of formal
      courses, through teaching workshops in the library, through one-on-one
      consultations, and by other methods. Librarians with backgrounds from art history
      to doctoral degrees in genetics have worked to establish these programs.
      CONCLUSION: Successful bioinformatics support programs can be established in
      libraries in a variety of different settings and by staff with a variety of
      different backgrounds and approaches.

PMID- 16888665
TI  - Design and implementation of a library-based information service in molecular
      biology and genetics at the University of Pittsburgh.
AB  - SETTING: In summer 2002, the Health Sciences Library System (HSLS) at the
      University of Pittsburgh initiated an information service in molecular biology
      and genetics to assist researchers with identifying and utilizing bioinformatics
      tools. PROGRAM COMPONENTS: This novel information service comprises hands-on
      training workshops and consultation on the use of bioinformatics tools. The HSLS
      also provides an electronic portal and networked access to public and commercial
      molecular biology databases and software packages. EVALUATION MECHANISMS:
      Researcher feedback gathered during the first three years of workshops and
      individual consultation indicate that the information service is meeting user
      needs. NEXT STEPS/FUTURE DIRECTIONS: The service's workshop offerings will expand
      to include emerging bioinformatics topics. A frequently asked questions database
      is also being developed to reuse advice on complex bioinformatics questions.

PMID- 16888666
TI  - Developing library bioinformatics services in context: the Purdue University
      Libraries bioinformationist program.
AB  - SETTING: Purdue University is a major agricultural, engineering, biomedical, and
      applied life science research institution with an increasing focus on
      bioinformatics research that spans multiple disciplines and campus academic
      units. The Purdue University Libraries (PUL) hired a molecular biosciences
      specialist to discover, engage, and support bioinformatics needs across the
      campus. PROGRAM COMPONENTS: After an extended period of information needs
      assessment and environmental scanning, the specialist developed a week of focused
      bioinformatics instruction (Bioinformatics Week) to launch system-wide, library
      based bioinformatics services. EVALUATION MECHANISMS: The specialist employed a
      two-tiered approach to assess user information requirements and expectations. The
      first phase involved careful observation and collection of information needs in
      context throughout the campus, attending laboratory meetings, interviewing
      department chairs and individual researchers, and engaging in strategic planning
      efforts. Based on the information gathered during the integration phase, several
      survey instruments were developed to facilitate more critical user assessment and
      the recovery of quantifiable data prior to planning. NEXT STEPS/FUTURE
      DIRECTIONS: Given information gathered while working with clients and through
      formal needs assessments, as well as the success of instructional approaches used
      in Bioinformatics Week, the specialist is developing bioinformatics support
      services for the Purdue community. The specialist is also engaged in training PUL
      faculty librarians in bioinformatics to provide a sustaining culture of library
      based bioinformatics support and understanding of Purdue's bioinformatics-related
      decision and policy making.

PMID- 16888667
TI  - The University of Washington Health Sciences Library BioCommons: an evolving
      Northwest biomedical research information support infrastructure.
AB  - SETTING: The University of Washington Health Sciences Libraries and Information
      Center BioCommons serves the bioinformatics needs of researchers at the
      university and in the vibrant for-profit and not-for-profit biomedical research
      sector in the Washington area and region. PROGRAM COMPONENTS: The BioCommons
      comprises services addressing internal University of Washington, not-for-profit,
      for-profit, and regional and global clientele. The BioCommons is maintained and
      administered by the BioResearcher Liaison Team. The BioCommons architecture
      provides a highly flexible structure for adapting to rapidly changing resources
      and needs. EVALUATION MECHANISMS: BioCommons uses Web-based pre- and post-course
      evaluations and periodic user surveys to assess service effectiveness. Recent
      surveys indicate substantial usage of BioCommons services and a high level of
      effectiveness and user satisfaction. NEXT STEPS/FUTURE DIRECTIONS: BioCommons is
      developing novel collaborative Web resources to distribute bioinformatics tools
      and is experimenting with Web-based competency training in bioinformation
      resource use.

PMID- 16888668
TI  - Carving a niche: establishing bioinformatics collaborations.
AB  - OBJECTIVES: The paper describes collaborations and partnerships developed between
      library bioinformatics programs and other bioinformatics-related units at four
      academic institutions. METHODS: A call for information on bioinformatics
      partnerships was made via email to librarians who have participated in the
      National Center for Biotechnology Information's Advanced Workshop for
      Bioinformatics Information Specialists. Librarians from Harvard University, the
      University of Florida, the University of Minnesota, and Vanderbilt University
      responded and expressed willingness to contribute information on their
      institutions, programs, services, and collaborating partners. Similarities and
      differences in programs and collaborations were identified. RESULTS: The four
      librarians have developed partnerships with other units on their campuses that
      can be categorized into the following areas: knowledge management, instruction,
      and electronic resource support. All primarily support freely accessible
      electronic resources, while other campus units deal with fee-based ones. These
      demarcations are apparent in resource provision as well as in subsequent support
      and instruction. CONCLUSIONS AND RECOMMENDATIONS: Through environmental scanning
      and networking with colleagues, librarians who provide bioinformatics support can
      develop fruitful collaborations. Visibility is key to building collaborations, as
      is broad-based thinking in terms of potential partners.

PMID- 16888669
TI  - Challenges and strategies of the Genetics Home Reference.
AB  - OBJECTIVE: This paper focuses on the first two years of operation of Genetics
      Home Reference (GHR), a Web-based resource <http://www.ghr.nlm.nih.gov> for the
      general public that helps to explain the health implications of findings from the
      Human Genome Project. METHODS AND FINDINGS: Key challenges of Web-based consumer
      health communication encountered in the growth and maintenance of GHR are
      discussed: prioritizing topics for GHR, streamlining the development process
      while keeping genetic information accurate, and designing a system that helps
      consumers navigate complex genetic relationships. Various strategies are used to
      address these challenges. Tying content development to topics of national
      priority and addressing topics requested by users makes the site increasingly
      important for both consumers and health professionals. Informatics methods are
      essential for quality control, particularly for genetic information that changes
      frequently. Indexing and hierarchical browsing features help to facilitate
      navigation. CONCLUSIONS: GHR is a credible, dynamic Website that uses lay
      language to explain the effects of genetic variation on human health. Informatics
      strategies are key to effective management of a large and expanding body of
      genetics information. Feedback from formal and informal sources indicates
      increasing usage and favorable acceptance of GHR.

PMID- 16888670
TI  - GeneTests: an online genetic information resource for health care providers.
AB  - OBJECTIVE: This paper describes the GeneTests genetic testing information
      resource with a focus on the GeneReviews component. METHODS AND FINDINGS: The
      need for authoritative genetic testing information and issues in the development
      and maintenance of GeneReviews are discussed: Hampered by lack of currency and
      content deficits, traditional medical information resources such as textbooks and
      the published literature are generally inadequate sources of genetic testing
      information. Problems encountered in developing GeneReviews include the evolution
      of new authorship models and academic and genetics professionals' skepticism
      about the quality of Web-based publications. CONCLUSIONS: GeneTests is an
      authoritative, highly used, and well-regarded resource in the international
      medical community that is intended for health care providers. Future development
      issues to address include ways to (1) manage the increasing editing and updating
      load as content grows and (2) address technical and content issues that need to
      be considered in displaying GeneReviews as a "just in time" resource in the
      electronic medical record to achieve the project goal of integrating appropriate
      use of genetic testing into patient care.

PMID- 16888671
TI  - [Study of drugs against neoplastic metastasis].
AB  - Further progress in the therapy of malignant diseases is expected from the
      introduction of potent antimetastatic drugs. Surveying of the complex and multi
      step behavior of the metastatic process, compounds showing inhibitory action
      against tumor cell migration may be ranked among the promising antimetastatic
      agents. Our present study indicate, however, that the antimigratory actions of
      certain antitumor drugs (doxorubicin, taxol), and inhibitors of signal
      transduction (PD-98059, LY-294002, SB-203580) are highly dependent on the assay
      applied (Boyden-chamber, 3D ECM cell culture). It has been proposed that agents
      interrupting cell-extracellular matrix contacts (hexyldeoxyuridine, borrelidin)
      and others interfering with the regulatory mechanism of gene translation
      (rapamycin, ribavirin) could be regarded as leading compounds in the
      antimetastatic drug development process. Nevertheless, for introducing
      diagnostically based targeted therapy the forthcoming tasks must include the
      further elucidation of the molecular mechanisms implicated in the amoeboid and
      cluster type of cell migration.

PMID- 16888672
TI  - [Tumor stem cells--a possible scenario].
AB  - More and more evidence support that tumors arise from somatic stem cells or from
      cells, either progenitors or differentiated ones, with the properties of
      stemness. It is a question whether all tumor cells have the capacity for self
      renewal and unlimited growth or only a fraction of them, i.e. the tumor stem
      cells. The concept is challenging, since the existence of tumor stem cells has an
      important practical consequence: only stem cells should be removed or stopped in
      order to control the tumor, while the other cells have temporary proliferative
      capacity.

PMID- 16888673
TI  - [Hepatocarcinogenesis in human liver].
AB  - Due to the development of the imaging techniques and liver surgery, pathologists
      are encountered more frequently with preneoplastic liver lesions. Well-defined
      stages of human hepatocarcinogenesis have been distinguished recently. Dysplastic
      foci represent the earliest stage of this process. Small-cell dysplastic foci are
      tumor precursors, but the large-cell form of this lesion does not progress
      further. The next stage is the dysplastic nodule, this larger lesion can be
      recognized by imaging techniques and gross examination of the specimen. Low- and
      high-risk forms are distinguished based on the level of cytological and
      structural atypia. The small hepatocellular carcinomas have a diameter of less
      than 2 cm by definition. The small HCC of indistinctly nodular type is equivalent
      of in situ carcinomas in other organs and designated sometimes as early HCC. The
      small HCC of the distinctly nodular type can be interpreted as advanced cancer
      despite its small size. The distinction between these lesions can be facilitated
      by ancillary techniques. The so-called capillarization of the liver sinusoids
      during the progression is characterized by the increased expression of
      endothelial markers as CD31 and CD34. Immunostaining for CD44, beta-catenin and
      p53 has prognostic value. Molecular biological techniques reveal gradual
      epigenetic and DNA changes during the process of hepatocarcinogenesis. Global
      gene expression profiling of hepatocellular carcinomas may result in a new
      classification of this tumor and can reveal new potential therapeutic targets.

PMID- 16888674
TI  - [Role of syndecan-1 proteoglycan in the invasiveness of HT-1080 fibrosarcoma].
AB  - Syndecan-1 is a transmembrane heparan sulfate proteoglycan which plays pivotal
      role in cell-cell and cell-extracellular matrix interactions. However, its
      implication in the establishment of malignant phenotype is still controversial.
      Its expression indicates differentiated phenotype in certain tumors, while it
      confers invasive nature for others. For the better understanding of the role of
      syndecan-1 in cancer we transfected HT-1080 fibrosarcoma cell line with the full
      and a truncated construct of syndecan-1 and established stable cell lines with
      them. We studied the in vitro and in vivo growth capacity and metastatic
      potential of the transfectants in comparison with the cell line bearing only the
      EGFP expression vector. Our results showed that the growth rate of syndecan
      transfectants increased and they developed more lung metastases than the control
      cells. As local growth of the full transfectant was faster than that of the 78sig
      we presume that the full protein and maybe the shedding is needed for the local
      development of the tumor, but the intracellular and transmembrane domain is
      sufficient to promote metastasis formation.

PMID- 16888675
TI  - [Imaging technics in bronchology].
AB  - Bronchoscopic imaging and diagnostics are tightly connected with radiological and
      pathological techniques. While computer tomography (virtual bronchoscopy) makes
      possible to mimic a realistic endobronchial situation, autofluorescent
      bronchoscopy holds significant potential to discover precancerous lesions not
      identifiable by standard bronchoscopy. Endoscopic ultrasound and fluoroscopy can
      be applied in order to obtain images and tissue samples from the extrabronchial
      areas. Electromagnetic navigation during flexible bronchoscopy, a novel
      technology that facilitates approaching peripheral lung lesions, involves
      creating an electromagnetic field around the thorax and localizing an endoscopic
      tool using a microsensor overlaid upon previously acquired CT images. In
      conclusion, parallel use of invasive and non-invasive imaging has the potential
      for considerable improvements in the diagnostic possibilities of routine
      bronchoscopic procedures.

PMID- 16888676
TI  - [Correlations of insulin resistance and neoplasms].
AB  - Insulin resistance is a worldwide risk factor for the two most dangerous human
      disease groups; namely, for cardiovascular lesions and malignancies. The insulin
      resistance syndrome have five basic criteria: hyperglycemia, visceral obesity,
      elevated serum triglyceride level, low HDL-cholesterol level (dyslipidemia) and
      hypertension. Each of these criteria alone are risk factors for cancer, and they
      mean together a multiple risk. Insulin resistance of the liver, skeletal muscles,
      and fatty tissue leads to a reactive hyperinsulinemia by the increased secretory
      activity of the beta-cells. Insulin has diverse metabolic effects, and at the
      same time is a growth factor. It enhances the production and mitogenic activity
      of other, insulin-like growth factors, and leads to pathological cell
      proliferation. In the uncompensated phase of insulin resistance hyperglycemia
      appears, which promotes tumor genesis by several pathways. The elevated serum
      glucose level is advantageous for the increased DNA synthesis of the tumor cells.
      It provokes deliberation of free radicals, which will cause derangement of both
      the DNA and the enzymes having a role in the repair mechanisms. Hyperglycemia
      leads to a nonenzymatic glycation of protein structures, and the glycated
      products enhance the deliberation of free radicals, cytokines and growth factors.
      Insulin resistance means an enhanced risk for breast, pancreas, liver, colon,
      bladder, prostate and oral cavity cancers. The moderately increased fasting
      glucose level is also a risk factor for breast, stomach and colon cancers, even
      without manifestation of type 2 diabetes. Insulin resistance promotes tumor
      progression as well. In cancer patients with hyperglycemia or type 2 diabetes,
      the rate of tumor recurrence, metastatic spread and fatal outcome is higher as
      compared with the tumor patients without metabolic disease. The correlation
      between insulin resistance and tumor promotion reveals new possibilities in the
      prevention and treatment of cancer. The healthy diet, physical activity and
      weight loss increase insulin sensitivity, and decrease the risk for both
      cardiovascular diseases and malignancies.

PMID- 16888677
TI  - [Changes in gene expression in the course of proliferative processes in the
      parathyroid gland].
AB  - The aim of this study was to investigate the changes in expression pattern of the
      most important genes connected with apoptosis in proliferative apoptotic lesions
      (hyperplasia, adenoma), applying cDNA microarray technique, in order to promote
      the possible diagnostic or therapeutic utilisation of any difference in gene
      expression compared to the healthy (normal) parathyroid gland. Samples were taken
      from surgically removed 2 hyperplasias, 2 adenomas and 2 normal parathyroid
      glands. The Apoptosis Gene Array (Superarray) was used. This contains 112 genes,
      in tetraspot arrangement. The probes measured 250-600 base pairs. Streptavidin
      was bound to the array. CDP Star TM chemiluminescent substrate was used for
      detection. The samples deriving from hyperplasia or adenoma were compared to
      samples from normal parathyroid glands. The following genes were overexpressed in
      both hyperplasia and adenoma: CHEK1, ATM, BCL-XL, FAS, TNF, cIAP1, TRAIL, FADD,
      CASP 4,5,6,8, CD120b, CD137, LTA, TANK, TARF2, CAD, LIGHTR, DR3LG. CASP1,10,
      BFAR, BOD, BCL2L2, TRANCE were underexpressed in both hyperplasia and adenoma.
      Genes overexpressed only in hyperplasia were: MDM2, MCL1, BCL2A1, BLK, RIPK2,
      CD40LG, TRAF5, HUS1, BNIP3. Underexpressed only in hyperplasia: BOK, CIDEA,
      TRAF1, TRIP. Overexpressed only in adenoma: APOLLON, RIPK1, LTB, LTBR, CASP2,13,
      cIAP2, CIDEB. Underexpressed only in adenoma: TRAF4 and FASLG. Overexpresion or
      underexpression meant 1.5-fold difference from normal average values. As a result
      of this study, both pro-apoptotic and antiapoptotic genes were identified in
      hyperplasia and adenoma of the parathyroid gland. It seems that increased
      proliferation is connected also with increased apoptotic activity, but tumor cell
      candidates are able to survive, by activation of signal pathways resulting in
      overexpresion of anti-apoptotic genes.

PMID- 16888678
TI  - [Rationale of antiangiogenic therapy].
AB  - Vascularization of cancer is a complex and heterogenous process where
      neoangiogenesis by sprouting is only one of the possible mechanisms that also
      include postnatal vasculogenesis, vessel incorporation, intussusceptive
      microvascular growth, glomeruloid angiogenesis and vascular mimicry. Furthermore,
      the mechanism of vascularization may also depend on the cancer type and the host
      tissue as well. Antivascular agents can be divided into angiosuppressive ones
      (endothelial cell proliferation inhibitors), vascular-targeted agents
      (microvessel disrupting agents) and anti-hypoxia agents (targeting the molecular
      pathways responsible for the development of the angiogenic phenotype). Since
      antivascular therapy is a special form of targeted therapy, it is necessary to
      apply it in a rational manner to consider the type of vascularization, the
      molecular background of the angiogenic phenotype, the stage of the disease and
      the standard anticancer therapy. Whithout such a fine-tuning, antivascular
      therapies cannot be integrated more successfully into the management of cancer
      patients.

PMID- 16888679
TI  - [The state of health of oncology nurses characterized by genetic and
      immunotoxicologic biomarkers].
AB  - Statistical data indicate a chronic shortage of work-force due to overwork, ill
      health state and increased risk of chronic noninfectious diseases in Hungarian
      health care personnel, which needs investigations in order to decrease the risk.
      Nurses of oncology units, often exposed to carcinogens when preparing and
      handling cytostatic drugs, are especially at high risk. In the present
      publication we report a complex clinical, geno- and immunotoxicology risk
      assessment of altogether 500 nurses, performed during the last 10 years at
      various oncology units in Hungary. The obtained results indicate that the health
      status of nurses at oncology units is better than the Hungarian average,
      especially of hypertonia and type II diabetes. However, the prevalence of iron
      deficiency anemia and different thyroid gland diseases is significantly higher
      than those of the controls matched for sex and age. The results suggest that iron
      deficiency can potentiate the resistance to insulin, i.e. the persistence of iron
      deficiency may increase the serum glucose levels and thus the risk of diabetes.
      Among the studied geno- and immunotoxicology biomarkers, the frequency of
      chromosome aberrations, sister chromatid exchange and B lymphocytes was
      significantly increased compared to the matched controls. The obtained
      alterations demonstrate the occupational exposure of the nurses to cytostatic
      drugs, thus the introduction of more strict hygienic controls and compliance with
      the European Union chemical safety regulations is necessary.

PMID- 16888680
TI  - [Familial pancreatic cancer].
AB  - Familial clustering is estimated in 5-10% of pancreatic cancers. In different
      countries Familial Pancreatic Cancer Registries have been established to
      investigate the epidemiology, and genetic background in these families and, to
      organize the screening programs for high-risk relatives and for follow-up. The
      largest such registry is found at Johns Hopkins University Hospital. Evaluating
      the available data revealed that familial pancreatic cancer is heterogeneous: it
      may occur in kindreds of pancreatic cancer patients, but it may also be
      associated with various familial cancer syndromes. Such syndromes include FAMMM
      syndrome, hereditary breast cancer, Peutz-Jeghers syndrome, but other
      associations can also be taken into account. The germline mutations are also
      heterogeneous, and although they are not absolutely decisive, they significantly
      increase the risk of the affected persons, making the organ more susceptible for
      environmental carcinogens. High-risk family members should be screened for gene
      mutations (especially for BRCA2, STK11/LKB1, CDKN2A/p16, PRSS1 genes), and by
      using endoscopic ultrasound. These methods are useful for identifying the
      preneoplastic conditions, but of equal importance is the cessation of smoking. In
      Hungary there are no relevant data about the epidemiology of familial pancreatic
      cancer, but their number is estimated to be about 80-150 annually. Considering
      the very high (and continuously increasing) incidence, it seems to be necessary
      to register and screen these families. This review emphasizes the importance of
      these goals.

PMID- 16888681
TI  - Dual androgen-response elements mediate androgen regulation of MMP-2 expression
      in prostate cancer cells.
AB  - AIM: To characterize the matrix metalloproteinases (MMP)-2 promoter and to
      identify androgen response elements (AREs) involved in androgen-induced MMP-2
      expression. METHODS: MMP-2 mRNA levels was determined by reverse transcription
      polymerase chain reaction (RT-PCR). MMP-2 promoter-driven luciferase assays were
      used to determine the fragments responsible for androgen-induced activity.
      Chromatin-immunoprecipitation assay and electrophoretic mobility shift assays
      (EMSA) were used to verify the identified AREs in the MMP-2 promoter. RESULTS:
      Androgen significantly induced MMP-2 expression at the mRNA level, which was
      blocked by the androgen antagonist bicalutamide. Deletion of a region
      encompassing base pairs -1591 to -1259 (relative to the start codon) of the MMP-2
      promoter led to a significant loss of androgen-induced reporter activity.
      Additional deletion of the 5'-region up to -562 bp further reduced the androgen
      induced MMP-2 promoter activity. Sequence analysis of these two regions revealed
      two putative ARE motifs. Introducing mutations in the putative ARE motifs by site
      directed mutagenesis approach resulted in a dramatic loss of androgen-induced MMP
      2 promoter activity, indicating that the putative ARE motifs are required for
      androgen-stimulated MMP-2 expression. Most importantly, the androgen receptor
      (AR) interacted with both motif-containing promoter regions in vivo in a
      chromatin immunoprecipitation assay after androgen treatment. Furthermore, the AR
      specifically bound to the wild-type but not mutated ARE motifs-containing probes
      in an in vitro EMSA assay. CONCLUSION: Two ARE motifs were identified to be
      responsible for androgen-induced MMP-2 expression in prostate cancer cells.

PMID- 16888682
TI  - Single nucleotide polymorphism C677T in the methylenetetrahydrofolate reductase
      gene might be a genetic risk factor for infertility for Chinese men with
      azoospermia or severe oligozoospermia.
AB  - AIM: To analyze the distribution of the single nucleotide polymorphism (SNP)
      C677T in the methylenetetrahydrofolate reductase (MTHFR) gene in 355 infertile
      Chinese patients with idiopathic azoospermia or severe oligozoospermia and 252
      fertile Chinese men as controls to explore the possible association of the SNP
      and male infertility. METHODS: Using the polymerase chain reaction (PCR)
      restriction fragment length polymorphism technique, the allele and genotype
      distribution of SNP C677T in the MTHFR gene were investigated in both patients
      and controls. RESULTS: The frequencies of allele T (40.9% vs 30.4%, P = 0.002,
      odds ration [OR] = 1.58, 95% confidence interval [CI]: 1.24-2.02) and mutant
      homozygote (TT) (18.3% vs. 11.5%, P=0.023, OR=1.72, 95% CI: 1.07-2.76) as well as
      carrier with allele (TT + CT) (63.4% vs. 49.2%, P = 0.0005, OR = 1.79, 95% CI:
      1.29-2.48) in infertile patients were significantly higher than those in
      controls. After patient stratification, the significant differences in
      distribution of the SNP between each patient subgroup and control group still
      remained. CONCLUSION: Our findings indicate that there is an association of SNP
      C677T in the MTHFR gene with male infertility, suggesting that this polymorphism
      might be a genetic risk factor for male infertility in Chinese men.

PMID- 16888683
TI  - Gene therapy and erectile dysfunction: the current status.
AB  - Current available treatment options for erectile dysfunction (ED) are effective
      but not without failure and/or side effects. Although the development of
      phosphodiesterase type 5 (PDE5) inhibitors (i.e. sildenafil, tadalafil and
      vardenafil) has revolutionized the treatment of ED, these oral medications
      require on-demand access and are not as effective in treating ED related to
      diabetic, post-prostatectomy and severe veno-occlusive disease states.
      Improvement in the treatment of ED is dependent on understanding the regulation
      of human corporal smooth muscle tone and on the identification of relevant
      molecular targets. Future ED therapies might consider the application of
      molecular technologies such as gene therapy. As a potential therapeutic tool,
      gene therapy might provide an effective and specific means for altering
      intracavernous pressure "on demand" without affecting resting penile function.
      However, the safety of gene therapy remains a major hurdle to overcome before
      being accepted as a mainstream treatment for ED. Gene therapy aims to cure the
      underlying conditions in ED, including fibrosis. Furthermore, gene therapy might
      help prolong the efficacy of the PDE5 inhibitors by improving penile nitric oxide
      bioactivity. It is feasible to apply gene therapy to the penis because of its
      location and accessibility, low penile circulatory flow in the flaccid state and
      the presence of endothelial lined (lacunar) spaces. This review provides a brief
      insight of the current role of gene therapy in the management of ED.

PMID- 16888684
TI  - Cross-sectional and longitudinal studies on interaction between bladder
      compliance and outflow obstruction in men with benign prostatic hyperplasia.
AB  - AIM: To explore the interaction between bladder compliance (BC) and bladder
      outflow obstruction (BOO) in men with benign prostatic hyperplasia (BPH) using
      cross-sectional and longitudinal studies. METHODS: A total of 181 men with BPH
      were recruited, and 100 of them were followed for one year. Cystometry was
      performed in a standing or a sitting position with 30 mL/min infusion. BC was
      manually corrected and defined. Obstruction coefficient (OCO), linear passive
      urethral resistance relation and international continence society (ICS) nomogram
      were used to diagnose BOO. The obstructed parameters were compared between the
      reduced BC group and the non-reduced group. BC was compared between the first
      investigation at the beginning of study and the second investigation at the end
      of study during the one-year follow-up period. RESULTS: The group with reduced BC
      had increased OCO and linear passive urethral resistance relation. BC was
      significantly lower in the obstructed group (55.7 mL/cm water) than that in
      unobstructed and equivocal one (74.9 mL/cm water, P <0.01). BC gradually reduced
      with the increased obstructed grade. There was a significantly weak negative
      correlation between BC and OCO (r = -0.132, P < 0.01). Over the one-year follow
      up period in the longitudinal study, BC for all men changed from 54.4 to 48.8
      mL/cm water (P >0.05), and BC for the group with BOO fell from 58.4 +/- 70.1 to
      46.5 +/- 38.7 mL/cm water (P>0.05). CONCLUSION: In men with BPH, a significant
      systematic decrease occurred in BC in the obstructed group and a significant
      systematic increase with urethral resistance occurred in the low BC group. A
      longitudinal study of the tendency of BC reduction in a group with BOO is
      necessary in the future.

PMID- 16888685
TI  - Persistent Muellerian duct syndrome with transverse testicular ectopia.
AB  - Persistent Muellerian duct syndrome (PMDS) is a rare form of male
      pseudohermaphrodism without the feature of ambiguous genitalia. We present a case
      of PMDS with transverse testicular ectopia (TTE).

PMID- 16888687
TI  - Surface tension in tears.

PMID- 16888688
TI  - [OCT: a new concept of diagnosis].

PMID- 16888686
TI  - [Medical and legal issues related to the drugs currently used in the treatment of
      Age-Related Macular Degeneration (ARMD)].

PMID- 16888689
TI  - [Autosomal dominant granular corneal dystrophy caused by a TGFBI gene mutation in
      a Mexican family].
AB  - OBJECTIVE: To describe the clinical data and the results of molecular analyses of
      the TGFBI gene in a patient with classic granular stromal corneal dystrophy (type
      I). METHODS: A female patient aged 60-years complaining of a long-standing
      decrease of visual acuity bilaterally associated with photophobia and foreign
      body sensation, underwent a complete ophthalmologic examination. Molecular
      analyses of DNA from the patient and from an affected brother included PCR
      amplification of exons 4, 11, 12, and 14 of the TGFBI gene and direct automated
      sequencing of the PCR products. RESULTS: The affected patient showed a pattern of
      corneal stromal lesions that was compatible with a diagnosis of classic granular
      dystrophy. No involvement of other corneal layers was evident. Molecular analysis
      disclosed a point mutation in exon 14 of the TGFBI gene which consisted of an
      adenine to guanine change at nucleotide position 1924, predicting a substitution
      of arginine instead of histidine at residue 626 of the TGFBI protein (H626R). An
      identical mutation was detected in DNA from her affected brother. CONCLUSIONS:
      This is the first time that a case of stromal granular dystrophy has been
      demonstrated to be caused by the H626R mutation, a molecular defect classically
      detected in the phenotypically distinct lattice corneal dystrophy. Our data
      indicate that the same molecular defects in the TGFBI gene lead to different
      phenotypes in stromal dystrophies, thus expanding the genotypic-phenotypic
      spectrum in this group of corneal diseases.

PMID- 16888690
TI  - [Identification of adenovirus associated with conjunctivitis by molecular
      methodology].
AB  - OBJECTIVE: To identify adenovirus in patients with conjunctivitis by molecular
      methods such as the Polymerase Chain Reaction (PCR) and DNA sequencing. METHODS:
      Samples of scrapings from the inferior fornix of 51 patients (39 diagnosed with
      Follicular Conjunctivitis and 12 diagnosed with Vernal Conjunctivitis) were
      processed by generic PCR to identify adenovirus. All the samples that were PCR
      positive were cultured on VERO cells for virus isolation, with this being
      demonstrated by immunofluorescence. For the identification of the isolated
      serotype, the multiplex PCR was utilized and DNA automated sequencing was
      employed to identify the genetic variants. RESULTS: Twenty-eight of the
      individuals diagnosed with Follicular Conjunctivitis and six of those diagnosed
      with Vernal Conjunctivitis, had positive results to adenovirus (67%). The
      cultures in VERO cells allowed the isolation of eight samples. Only three of the
      isolated viruses (one Ad1 and two Ad2) were identified by the multiplex PCR used
      to identify the subgenus C adenovirus. An Ad1 genetic variant was identified by
      automated sequencing while the Ad2 serotypes were identical to the ones reported
      by Genbank. CONCLUSIONS: The Polymerase Chain Reaction and DNA sequencing are
      useful tools to identify and characterize microorganisms responsible for diseases
      such as conjunctivitis caused by adenoviruses.

PMID- 16888691
TI  - [Utility of optic coherence tomography (OCT) in the follow-up of idiopathic
      intracranial hypertension in childhood].
AB  - PURPOSE: To show the utility of optic coherence tomography (OCT) in the follow up
      of the idiopathic intracranial hypertension (IIH) in childhood. METHODS: Three
      girls, aged between 4 and 11 years, were diagnosed and subsequently followed with
      the help of OCT for an episode of idiopathic intracranial hypertension. All of
      them had presented with non-specific symptoms such as visual disturbance,
      headache, stomach ache, and in one case diplopia and torticolis. Brain imaging
      studies were normal, however lumbar puncture found an elevated intracranial
      pressure. Visual fields were tested using Octopus automated perimetry and the
      optic nerve fiber layer (ONF) was measured by OCT at each of the attendances.
      RESULTS: The visual acuity was normal in all cases, but two girls had evidence of
      an abducens nerve palsy. Fundus biomicroscopy revealed marked papilledema. The
      thickness of the ONF was increased 2-3 times over normally expected levels. The
      follow up and the treatment with prednisone and azetazolamide was monitored by
      OCT, with a good outcome and return of the ONF levels to normal. In one case,
      however, a recurrence was detected after three months without treatment.
      CONCLUSION: IIH in childhood is an uncommon condition, often with a different
      presentation from what is seen in teenagers and adults. OCT is a useful technique
      helping in both the diagnosis and the follow-up of this disorder in children
      (Arch Soc Esp Oftalmol 2006; 81: 383-390).

PMID- 16888692
TI  - [Expression of B7 molecules and TLR-9 on corneal epithelial cells infected with
      adenovirus: clinico-pathological implications in viral keratoconjunctivitis].
AB  - PURPOSE: B7 molecules are a family of proteins that co-stimulate T cells during
      immune activation. Normally the corneal epithelial cells (CEC) do not express
      these molecules on their cell surface. Toll-like receptors play an important role
      in the innate immune response to invading pathogens and recently have been
      demonstrated to be expressed on mice cornea. The objective of this study was to
      determine whether adenoviral infection induces B7 molecules and TLR9 on human
      CEC. METHODS: CEC were isolated from human corneas treated with dispase-II, and
      grown in the presence of supplemented hormonal epithelial medium until
      confluence. Then CEC were then infected with adenovirus 5 (Ad5) and cultured for
      different times. The CEC were then recovered and stained against human CD80,
      CD86, TLR-9 and cytokeratin. All cells were analyzed by flow cytometry. RESULTS:
      Ad5 infection of CEC induced the expression of B7 molecules and TLR-9 after 24
      hours in culture, rising to maximum levels at 72 hours. B7 expression at 72 hours
      was as follows: CD80 expression on infected CEC was 62% (standard error [SE] 2.6)
      versus 3% (SE 1.2) on non-infected CEC (p<0.001); CD86 expression on infected CEC
      was 95% (SE 2.1) versus 5% (SE 1.2) on non-infected CEC (p<0.001). TLR-9
      expression at 72 hours was 80% (SE 1.2) on infected CEC versus 5% (SE 1) on non
      infected CEC (p<0.001). CONCLUSIONS: Ad5 infection induced the expression of B7
      molecules and TLR-9 on CEC.

PMID- 16888693
TI  - [Results of treatment of retinal angiomatous proliferation with photodynamic
      therapy].
AB  - PURPOSE: To determine the effects of phothodynamic therapy using verteporfin in
      the treatment of patients with retinal angiomatous proliferation (RAP) and the
      incidence of this retinal disease in our area. METHODS: We performed a
      retrospective study of 11 cases of RAP who were treated with photodynamic therapy
      using verteporfin (PDT). RESULTS: The incidence of RAP in the group of eyes with
      minimally classic or occult subfoveal choroidal neovascularization was 8%. The
      mean follow-up time after treatment was 15 months. The visual acuity improved in
      3, remained the same in 4, and decreased in 4. In 4 patients, angiomatous lesions
      were observed in both eyes. CONCLUSIONS: There is no method proven to be
      effective for the treatment of retinal angiomatous proliferation. Our results
      suggest that PDT may be useful therapy in patients with RAP as it appeared to
      reduce the risk of visual loss.

PMID- 16888694
TI  - [Side-effects of triamcinolone in young patients].
AB  - CASE REPORTS: Intravitreal triamcinolone is being increasingly employed for the
      treatment of macular diseases. We report two cases of intraocular pressure
      elevation and cataract formation after intravitreal triamcinolone therapy, and
      wonder if these complications are more likely when this agent is used in young
      patients. Intravitreal triamcinolone was injected into both eyes of the two young
      patients with chronic posterior and intermediate uveitis refractory to peribulbar
      and oral corticosteroid therapy. Chronic cystoid macular edema improved in both
      patients, however the intraocular pressure increased, requiring topical
      antihypertensive therapy, and this was followed by accelerated cataract
      formation. DISCUSSION: Young age and chronic inflammation could be associated
      with an intraocular pressure rise and subsequent cataract development after
      intravitreal triamcinolone.

PMID- 16888695
TI  - [Uveal effusion syndrome after strabismus surgery].
AB  - CASE REPORT: A woman was operated on for strabismus under topical anesthesia. An
      exudative conjunctivitis was diagnosed immediately after the surgery, and a uveal
      effusion syndrome diagnosed 15 days later. Surgery exploration, vycril suture
      removal and therapy with systemic, sub-tenon, and topical corticosteroid and
      antibiotics was initiated. Intraoperative culture revealed evidence of
      Staphylococcus epidermidis. Good resolution occurred in 4 months. DISCUSSION:
      Uveal effusion secondary to strabismus surgery has not been reported in the
      published literature. Implant and suture infection by Staphylococcus epidermidis
      following scleral buckling surgery may be a possible, but rare, cause of the
      uveal effusion syndrome.

PMID- 16888697
TI  - [Ophthalmic remedies in the Dioscorides' Materia Medica (IV)].

PMID- 16888696
TI  - [Retinal cholesterol embolization after coronary angiography].
AB  - CASE REPORT: We report a patient with multiple cholesterol retinal embolism in
      both eyes following coronary angiography. She also had associated renal, skin and
      cardiac manifestations of the Cholesterol Embolization Syndrome (CES) and died 10
      weeks later. Autopsy revealed cholesterol crystal emboli in several organs.
      DISCUSSION: Atheromatous plaques can be ruptured and displaced during a
      diagnostic catheterisation, and thus can be a potential source of these massive
      emboli. Retinal cholesterol crystals help to establish the diagnosis of the
      syndrome, particularly when other systemic manifestations exist. When this
      complication occurs, the prognosis can be devastating because of associated
      multiorgan failure.

PMID- 16888698
TI  - [Don't lose them!].

PMID- 16888699
TI  - [A young infant with afebrile pneumonia caused by Chlamydia trachomatis].
AB  - Pregnant women who have an urogenital Chlamydia trachomatis infection may
      transmit the infection to their infants. Conjunctivitis and nasopharyngeal
      infection are the most frequent manifestations. Less frequently the infants may
      develop pneumonia. We report a case of a 5-week-old girl with poor feeding,
      staccato cough and clinical signs of pneumonia. Chest radiography revealed severe
      bronchopneumonia. Despite of intravenous therapy with ampicillin and gentamicin
      respiration deteriorated and oxygen supplementation became necessary. After
      additional treatment with oral erythromycin (50 mg/kg per day) had been started
      the clinical condition improved. Polymerase chain reaction with a nasopharyngeal
      specimen was found to be positive for Chlamydia trachomatis.

PMID- 16888701
TI  - [The 109th Meeting of German Physicians in Magdeburg].

PMID- 16888702
TI  - A comparison of non-radioactive methods for assessing viability in ex vivo
      cultured cancellous bone: technical note.
AB  - Biocompatibility studies are carried out either in two dimensional monolayer
      culture or in animal studies. Bone organ cultures are therefore required in order
      to reduce the number of animal studies performed, while at the same time ensuring
      a more natural environment than that provided by monolayer culture of isolated
      cells. Due to the three dimensional nature of bone explants, assays that
      determine the distribution of viable cells are required, however dense
      mineralised bone is not easily penetrated by soluble factors. We sought to
      compare a number of non-radioactive viability methods in order to assess their
      suitability for use with cancellous bone. Fluorescent live/dead staining, MTT
      activity and lactate dehydrogenase detection were all investigated on either
      whole bone explants (9.5 mm in diameter, 5 mm high) or on sections of explants.
      All these assays are routinely used in 2 dimensional cell culture systems, yet
      each required modifications to be suitable for use with cancellous bone. Factors
      such as penetration of reagent, incubation time, assay temperature and ease of
      determining viable cells were all compared. It was demonstrated that penetration
      of the reagents into whole cores was a major problem which easily led to
      artefacts that could be overcome by preparing 250 mum unfixed sections.
      Fluorescent live/dead staining had extra complications caused by the
      autofluorescence of the bone generating a high signal to noise ratio, making
      assessment of osteocyte viability impossible. MTT staining was difficult to
      interpret due to the punctate nature of the stain. We found that lactate
      dehydrogenase staining of 250 mum thick unfixed sections led to excellent
      viability determination of osteocytes within the mineralised matrix. It also
      maintained marrow structure and enabled marrow viability to be assessed as a
      factor of volume occupied by viable marrow. Decreasing the viscosity of the LDH
      assay solution used in published methods led to a greatly improved penetration
      into the calcified matrix. Quantification of thick sections is aided by using the
      autofluorescence of the bone to highlight the darkly stained osteocytes against
      the fluorescing bone.

PMID- 16888704
TI  - Stress, self-efficacy and quality of life in cancer patients.
AB  - The purpose of the study was to examine the effect of different stressors on
      various domains of quality of life (QOL) in cancer patients. The study focused on
      testing a model describing interrelations between two kinds of stress
      antecedents, two mediating variables--perceived stress and self-efficacy--and
      QOL. The participants were 60 cancer patients of both genders and various
      diagnoses. They were administered questionnaires of background information, QOL,
      perceived stress and general self-efficacy. Two stress indices were defined
      empirically: health stress (based on advanced disease stage, long disease
      duration, and undergoing treatment) and social stress (based on unemployment,
      recent immigration, and older age). Confirmatory factor analysis enabled defining
      five factors of QOL. Hierarchical regression analyses showed that the index of
      social stress was related to more QOL scales than the index of health stress and
      very few interactions with the mediating variables. Structural equation modeling
      provided a more comprehensive and accurate view. It showed that the index of
      health stress affected QOL mainly through perceived stress, and that self
      efficacy affected QOL by reducing perceived stress and increasing QOL. The major
      conclusions are that QOL is affected negatively by both health stresses and
      social stresses, but the former are mediated primarily by the experience of
      perceived stress.

PMID- 16888703
TI  - Activation of lymphocyte proliferation by boronate-containing polymer immobilised
      on substrate: the effect of boron content on lymphocyte proliferation.
AB  - This study demonstrates that boronic acid-containing polymers coated onto solid
      support function as synthetic mitogens for mouse lymphocytes. The polymer was
      synthesized by radical copolymerization of 3-acrylamidophenylboronic acid with
      dimethylacrylamide (poly(AAPBA-DMAA)). The boronic acid in the trigonal form in
      the copolymer activated lymphocytes, probably by crosslinkage to glycoprotein
      moieties on the plasma membrane surface, as in the case of lectin stimulation. A
      higher concentration of phenylboronic acid on the copolymer surface resulted in
      greater activation of lymphocytes, suggesting that the number of phenylboronic
      acid residues per unit area may be a crucial factor in lymphocyte proliferation.
      The proliferative response of lymphocytes was also affected by the surface
      wettability, probably due to a difference in the flexibility of polymer strands
      at the cell-polymer interface.

PMID- 16888705
TI  - Contribution of fetal magnetic resonance imaging and amniotic fluid digestive
      enzyme assays to the evaluation of gastrointestinal tract abnormalities.
AB  - OBJECTIVE: To analyze the contribution of fetal magnetic resonance imaging (MRI)
      and amniotic fluid digestive enzyme (AFDE) assays to the evaluation of
      gastrointestinal tract abnormalities. METHODS: This was a prospective study
      involving 24 fetuses suspected of having gastrointestinal tract abnormalities on
      ultrasound examination. MRI was used to analyze the location of the obstruction,
      the visibility of the small bowel not involved in the obstruction, and the
      visibility and size of the colon and rectum. Abnormalities were further evaluated
      by AFDE assays. The final diagnosis was based on postnatal or fetopathological
      examination. RESULTS: In duodenojejunal obstructions, MRI (6/6) and AFDE assays
      (4/4) correctly identified the level of obstruction, but were less accurate for
      small bowel obstructions (MRI, 10/11; AFDE assays, 7/11). The small bowel not
      involved in the obstruction was correctly evaluated by MRI as being viable in six
      cases and as abnormal in eight cases (multiple obstructions or necrosis).
      However, it was thought antenatally to be abnormal by MRI in four cases in which
      it was found to be normal on postnatal findings. Three cases in which the colon
      was found to have abnormal echogenicity were considered normal both by MRI and
      AFDE assay, in agreement with postnatal findings. Two cases of microcolon
      megacystis-intestinal hypoperistalsis syndrome (MMIHS) were diagnosed both by MRI
      and AFDE assay. Of the three anorectal malformations, two were overlooked by
      ultrasonography and one by MRI. MRI also overlooked 2/3 associated rectourethral
      fistulas. CONCLUSION: MRI and enzyme analysis are good complementary tools to
      ultrasonography for identifying the level of gastrointestinal obstruction and
      diagnosing MMIHS. MRI can assess the normality of the intestinal tract not
      involved in the obstruction, but not multiple obstructions, necrosis and small
      urodigestive fistulas.

PMID- 16888706
TI  - Randomized clinical trial assessing the effect of Doppler-optimized fluid
      management on outcome after elective colorectal resection.
AB  - BACKGROUND: Protocolized fluid administration using oesophageal Doppler
      monitoring may improve the postoperative outcome in patients undergoing surgery.
      METHODS: A total of 108 patients undergoing elective colorectal resection were
      recruited into a double-blind prospective randomized controlled trial. An
      oesophageal Doppler probe was placed in all patients. The control group received
      perioperative fluid at the discretion of the anaesthetist, whereas the
      intervention group received additional colloid boluses based on Doppler
      assessment. Primary outcome was length of postoperative hospital stay. Secondary
      outcomes were morbidity, return of gastrointestinal function and cytokine markers
      of the systemic inflammatory response. Standard preoperative and postoperative
      management was used in all patients. RESULTS: Demographic and surgical details
      were similar in the two groups. Aortic flow time, stroke volume, cardiac output
      and cardiac index during the intraoperative period were higher in the
      intervention group (P<0.050). The intervention group had a reduced postoperative
      hospital stay (7 versus 9 days in the control group; P=0.005), fewer intermediate
      or major postoperative complications (2 versus 15 percent; P=0.043) and tolerated
      diet earlier (2 versus 4 days; P=0.029). There was a reduced rise in
      perioperative level of the cytokine interleukin 6 in the intervention group
      (P=0.039). CONCLUSION: A protocol-based fluid optimization programme using
      intraoperative oesophageal Doppler monitoring leads to a shorter hospital stay
      and decreased morbidity in patients undergoing elective colorectal resection.

PMID- 16888707
TI  - Echogenic foci in the dilated fetal colon may be associated with the presence of
      a rectourinary fistula.
AB  - Intraintestinal meconium calcification in the fetus and newborn is a rare
      finding, occurring in patients with intestinal obstruction. The intraluminal
      location of the enterolithiasis enables differentiation from calcifications that
      are secondary to bowel perforation and meconium peritonitis. We report on a term
      male neonate with VACTERL (vertebral defects, imperforate anus, cardiac
      anomalies, tracheoesophageal fistula, renal anomalies, limb anomalies)
      association and rectourethral fistula, in whom enterolithiasis was documented by
      prenatal ultrasound imaging at 21 weeks' gestation. A review of the literature
      and a summary of all previously described cases of neonates with intraluminal
      meconium calcifications are provided. Prenatal ultrasonographic detection of
      enterolithiasis in fetuses with anal atresia may indicate the presence of an
      enterourinary fistula.

PMID- 16888708
TI  - Ultrasound finding of an echogenic mass in women with secondary postpartum
      hemorrhage is associated with retained placental tissue.
AB  - OBJECTIVES: To describe sonographic findings associated with retained placental
      tissue in patients with secondary postpartum hemorrhage, and to compare these
      findings with those of women with a normal puerperium. METHODS: This was a
      prospective observational study of 79 women with secondary postpartum hemorrhage.
      Ultrasound examinations were performed on the day the patients presented with
      clinical symptoms and were scheduled for postpartum days 1, 3, 7, 14, 28 and 56,
      continuing until uterine surgical evacuation was performed or until the bleeding
      stopped. The maximum anteroposterior (AP) diameters of the uterus and uterine
      cavity were measured and morphological findings in the cavity were recorded. The
      findings were compared with previously published results from a normal
      population. RESULTS: The patients were divided into two groups. Group 1 (n = 18)
      underwent surgery and Group 2 (n = 61) was treated conservatively. Sonography
      revealed an echogenic mass in the uterine cavity in 17 patients from Group 1, and
      in 14 of these patients histology confirmed placental tissue. The AP diameter of
      the uterine cavity was above the 90(th) percentile in all but two of the 18 Group
      1 patients. In 18 patients from Group 2 the cavity was empty and in 43 a mixed
      echo pattern was found. The uterine cavity was wider compared with the controls,
      but the values largely overlapped. CONCLUSION: This report supports the opinion
      that the sonographic finding of an echogenic mass in the uterine cavity in women
      with secondary postpartum hemorrhage is associated with retained placental
      tissue.

PMID- 16888709
TI  - Dialysis-assisted two-dimensional gel electrophoresis.
AB  - 2-DE is an important tool in proteomics research. However, intrinsic gel-to-gel
      variability of 2-DE often masks the biological differences between the samples
      and compromises quantitative comparison of protein expression levels. Here, we
      describe a modification of 2-DE that results in improved matching and
      quantification of proteins. This was accomplished by performing IEF of two
      samples in two IPG strips separated by a dialysis membrane. After IEF running,
      the strips were separated and the SDS-PAGE dimension was accomplished on two
      individual gels. After gel staining with CBB, ImageMaster 2D Platinum software
      (Amersham) was used for spot detection and quantification. Analysis of protein
      extracts from C2C12 myoblasts by this method resulted in 99% spot-matching
      efficiency and CV in stain intensity (% volume) was less than 0.5 for 98% of
      spots. We conclude that this technique, called dialysis-assisted gel
      electrophoresis, gives superior spot matching and quantitative reproducibility
      compared to IEF conducted on separate strips.

PMID- 16888711
TI  - DNA profiling of shahtoosh.
AB  - The population of the Tibetan Antelope (Pantholops hodgsonii) has recently
      declined dramatically due to the illegal trade in its wool. The animal lives at
      high altitude and is protected from the extremely cold climate due to a coat of
      very fine wool. These hairs are highly sought for weaving a shawl called
      shahtoosh. The large-scale poaching of the antelope has resulted in the species
      being placed on CITES Appendix I. We report on a method of DNA profiling on a
      confiscated shahtoosh using the cytochrome b (cyt b) gene to produce a test that
      will identify unambiguously the presence of P. hodgsonii. Two shahtoosh samples
      were provided by the Council of Agriculture, Taiwan, and ten shawl samples of
      sheep wool (Ovis aries), cashmere from the Kashmir goat (Capra hircus), and
      pashmina from the Himalayan goat (C. hircus) were collected from local stores for
      comparison. Two primer pairs were used to amplify a 271 bp fragment of cyt b gene
      which would distinguish these three species. The resulting amplification products
      were directly sequenced. When the DNA sequences were compared with the sequences
      registered in GenBank and EMBL databases, the sequences with the highest homology
      were the cyt b genes of P. hodgsonii, C. hircus, and O. aries. This study
      demonstrates that there is still sufficient DNA present in the finished wool of a
      shahtoosh shawl to allow DNA typing and the method established was highly
      plausible to identify the CITES protected species.

PMID- 16888710
TI  - A novel sol-gel calix[4]arene-modified capillary column for open-tubular
      capillary electrochromatography.
AB  - A novel open-tubular CEC (OT-CEC) column was prepared by immobilized 5,11,17,23
      tetra-tert-butyl-25,27-diethoxy-26,28-dihydroxy-calix[4]arene (Calix[4]) on fused
      silica capillary column with sol-gel technology. Calix[4] was initially reacted
      with gamma-glycidoxypropyltrimethoxysilane (KH-560) to form a new sol-gel
      precursor (calix[4]-KH-560), and then mixed with another precursor, namely
      tetraethoxysilane (TEOS). After hydrolysis and condensation, a sol-gel matrix was
      obtained, in which calix[4] was incorporated. Successful calix[4]-modified sol
      gel coating was suggested by infrared (IR) spectra and greatly decreased EOF. In
      comparison with OT columns prepared by the sol-gel method with TEOS and KH-560
      only, the calix[4]-modified sol-gel column showed greatly improved separation of
      isomeric toluidines, nitrophenols, picolines and neurotransmitters with
      structural similarity. Migration time and theoretical plate number
      reproducibility were satisfactory with RSDs less than 1 and 6% each for within
      column runs and not more than 3 and 7% each for column-to-column measurements,
      using toluidine and nitrophenol isomers as test solutes on this column. High
      separation efficiencies (96,000-300,000 plates/m) for basic toluidine isomers
      were obtained. This column was also successfully employed to combine extraction
      procedure for the determination of dopamine (DA) and norepinephrine (NE) in
      Portulaca oleracea L. The recoveries of DA and NE were 93.3 and 94.2%,
      respectively.

PMID- 16888712
TI  - Synthesis of water-soluble phenylazosalicylaldehyde analogues and their
      application to capillary electrophoretic determination of primary amines.
AB  - Several primary amines are known to be endogenous substances, and they are to be
      detected at very low concentration level. Novel water-soluble azo dyes as
      precolumn derivatizing reagents were synthesized for the analysis of primary
      amines with strong visible-light absorption by CZE. A coupling reaction was used
      to introduce a sulfophenylazo group to salicylaldehyde or 1-hydroxy-2
      naphthaldehyde to extend the conjugation and to improve the solubility in water
      of the derivatizing reagents, as well as the target compounds of the reaction
      products with the primary amines. Two azo dyes of 5-(4
      sulfophenylazo)salicylaldehyde sodium salt (AZO1) and 4-(4-sulfophenylazo)-1
      hydroxy-2-naphthaldehyde sodium salt (AZO2) were synthesized. Separation of eight
      kinds of n-alkylamines was performed by CZE after the derivatization with AZO1 or
      AZO2. The addition of Brij 35 to the running electrolyte and to the sample
      solutions was necessary to improve the solubility and the resolution among the
      analytes. Both reagents, AZO1 and AZO2, were compared with each other in terms of
      the reaction time of derivatization, the detection sensitivity and the total
      analysis time. The derivatization process using AZO2 was applied to the
      determination of four biogenic amines, histamine, tyramine, cadaverine and
      putrescine, and LODs at around micromolar level were achieved for the four
      amines.

PMID- 16888714
TI  - Identification of microbial mixtures by LC-selective proteotypic-peptide analysis
      (SPA).
AB  - This paper describes a method--using a combination of LC-MS/MS of selected
      bacteria-specific peptides and database search--for determining the species of
      bacteria present in a mixture. We identified the proteotypic peptides that were
      associated with specific bacteria by searching protein databases for the LC-MS/MS
      data. The retention time windows for specific peptide markers were used as an
      extra constraint so that the peptide markers of many bacterial species could be
      analyzed in a single LC-selective proteotypic-peptide analysis (SPA). We
      performed LC-MS/MS analyses on the proteolytic digest of cell extracts and
      monitored only the selected marker peptide ions at given elution time windows.
      The corresponding bacterial species could be characterized when the selected
      peptides that eluted at expected elution windows were identified correctly from
      the database. We managed to identify up to eight bacterial species simultaneously
      during a single LC-MS/MS analysis, as well as bacteria mixed in various
      abundances. Two marker ions having similar values of m/z, but obtained from two
      different bacterial samples, which would otherwise be selected as precursors
      within mass tolerance and would complicate the MS/MS data, were time-resolved
      using LC and then used to correctly identify their bacterial sources. The
      coupling of selective MS/MS monitoring with separation methods, such as LC,
      provides a highly selective and accurate analytical method for characterizing
      complex mixtures of bacterial species.

PMID- 16888713
TI  - Mass spectrometry assisted assignments of binding and cleavage sites of
      copper(II) and platinum(II) complexes towards oxidized insulin B chain.
AB  - Interaction of cis-[Pt(en)(H2O)2]2+ and [CuL(H2O)]2+, where L is 2-[bis(2
      aminoethyl)amino]ethanol, with oxidized insulin B chain in molar ratio of 1 : 1,
      1 : 2 and 1 : 3 at pH 2.5 and 40 degrees C has been investigated by electrospray
      ionization mass spectrometry (ESI-MS) and tandem mass spectrometry (MS/MS). The
      results show that the binding sites of the two complexes with oxidized insulin B
      chain are terminal NH2, imidazole groups of His5 and His10. The hydrolytic
      cleavage studies show that the [CuL(H2O)]2+, upon a pendant hydroxyl group of the
      ligand, selectively cleaves the peptide bonds at Gly8-Ser9, Asn3-Gln4 and Phe1
      Val2, and the cis-[Pt(en)(H2O)2]2+ only cleaves the peptide bond at His10-Leu11.
      This is the first report of cis-[Pt(en)(H2O)2]2+-promoted cleavage of His-X
      peptide bond.

PMID- 16888715
TI  - Diastereomeric differentiation of peptides with CuII and FeII complexation in an
      ion trap mass spectrometer.
AB  - Complexation by transition metal ions (CuII and FeII) was successfully used to
      differentiate the diastereomeric YAGFL, YDAGFL and Y(D)AGF(D)L pentapeptides by
      electrospray ionization-ion trap mass spectrometry in the positive ion mode using
      low-energy collision conditions. This distinction was allowed by the
      stereochemical effects due to the (D)Leu/(L)Leu and the (D)Ala/(L)Ala residues
      yielding various steric interactions which direct relative dissociation rate
      constants of the binary [(M - H) + MeII]+ complexes (Me = Cu or Fe) subjected to
      low-energy, collision-induced dissociation processes. The interpretation of the
      collision-induced dissociation spectra obtained from the diastereomeric
      cationized peptides allowed the location of the deprotonated site(s), leading to
      the postulation of ion structures and fragmentation pathways for both the [(M -
      H) + CuII]+ and [(M - H) + FeII]+ complexes, which differed significantly. With
      CuII, consecutive fragmentations, initiated by the decarboxylation at C-terminus,
      were favored relative to sequence product ions. On the other hand, with FeII,
      competitive fragmentations resulting in abundant sequence product ions and
      significant internal losses were preferred. This could be explained by different
      localizations of the negative charge, which directs the orientation of both the
      [(M - H) + CuII]+ and [(M - H) + FeII]+ binary complexes fragmentations. Indeed,
      the free negative charge of the [(M - H) + CuII]+ ions was mainly located at one
      oxygen atom: either at the C-terminal carboxylic group or, to a minor extent, at
      the Tyr phenol group (i.e. zwitterionic forms). On the other hand, the negative
      charge of the [(M - H) + FeII]+ ions was mainly located at one of the nitrogen
      atoms of the peptide backbone and coordinated to FeII (i.e. salt non-zwitterionic
      form).Moreover, this study reveals the particular behavior of CuII reduced to
      CuI, which promotes radical losses not observed from the peptide-FeII complexes.
      Finally, this study shows the analytical potentialities of the complexation of
      transition metal ions with peptides providing structural information
      complementary to that obtained from low-energy, collision-induced dissociation
      processes of protonated or deprotonated peptides.

PMID- 16888716
TI  - Structure elucidation of cyclic pyoverdins and examination of rearrangement
      reactions in MS/MS experiments by determination of exact product ion masses.
AB  - Structure elucidation of naturally occurring linear and cyclic peptidic compounds
      can be complicated by rearrangement reactions induced upon collision activation
      (CA) when parts of the molecule migrate, suggesting incorrect substitution
      patterns. Such complex rearrangements are examined and discussed for two iron
      complexing compounds produced by the bacterial genus Pseudomonas (so-called
      pyoverdins). Various MS2- and MS3-product ion experiments were performed using a
      quadrupole-ion trap (QIT) at low resolution and a FT-ICR at high resolution
      allowing accurate mass determinations. The results of the multidimensional study
      confirm the proposed processes. On the basis of the series of tandem-MS
      experiments the structure of a new pyoverdin from a P. fluorescens strain
      [PVD(D47)] is deduced.

PMID- 16888717
TI  - Metabolite profile of sibutramine in human urine: a liquid chromatography
      electrospray ionization mass spectrometric study.
AB  - We present a detailed experimental approach to detection and subsequent
      structural characterization of unknown metabolites of sibutramine, using liquid
      chromatography-mass spectrometric techniques. The full-, precursor ion, and
      constant neutral loss scan modes of a triple quadrupole mass spectrometer were
      used for screening sibutramine metabolites in human urine. The structural
      assessment of unknown metabolites was based on MSn ion trap mass spectrometric
      analysis and comparison of MSn spectra between the standards and compounds
      detected. Two phase-I (M1 and M2) and eight phase-II (M3-M6) metabolites of
      sibutramine were found in human urine. Metabolites M1 and M2, which were found as
      minor metabolites, originated from N-demethylation of sibutramine. Carbamoyl
      glucuronides formed from metabolites M1, M2, and their hydroxylated analogs were
      the main metabolites of sibutramine and were characterized by tandem mass
      spectrometric analysis and by the chemical modification of their structure. We
      demonstrate the usefulness of the chemical derivatization approach for estimation
      of the site of glucuronidation and propose the formation of hydroxylated
      regioisomers of metabolites M4 and M6.

PMID- 16888718
TI  - Decomposition of health inequality by determinants and dimensions.
AB  - The study integrates two methodologies so that income-related inequality in
      general health can be decomposed into contributions from socio-demographic
      characteristics to each of the dimensions defining general health. It is found
      that these relative contributions vary substantially across dimensions. For
      policy purposes such information is valuable as it indicates at which population
      groups and at which aspects of health efforts to reduce inequalities in health
      should be targeted.

PMID- 16888720
TI  - A comprehensive dictionary of protein accession codes for complete protein
      accession identifier alias resolving.
AB  - In mass spectrometry-based proteomics, protein identification results usually
      consist of peptide sequences and database-dependent accession identifiers of the
      matching proteins. Often certain annotations are only available in particular
      databases that in turn must be queried by a certain identifier. In order to
      simplify and unify the tracing of identified proteins back to their original
      annotation information, a system capable of set-oriented mapping the different
      accession identifiers of proteins derived from multiple sequence database sources
      has been developed. This allows unification of the access to protein information
      and tracing to other online resources providing additional information as well as
      resolving cross-references of protein identifications. The interface of seqDB is
      available via http://www.protein-ms.de following the link to seqDB.

PMID- 16888721
TI  - Identification of blottin: a novel gastric trefoil factor family-2 binding
      protein.
AB  - The trefoil factor family (TFF) peptides are important in gastro-intestinal
      mucosal protection and repair. Their mechanism of action remains unclear and
      receptors are sought. We aimed to identify and characterise proteins binding to
      TFF2. A fusion protein of mouse TFF2 with alkaline phosphatase was generated and
      used to probe 2-D protein blots of mouse stomach. The resulting spots were
      analysed by MS. The protein identified was characterised by bioinformatics, rapid
      amplification of cDNA ends, in situ hybridisation (ISH) and immunohistochemistry
      (IHC). Functional assays were performed in gastrointestinal cell lines. A single
      major murine protein was identified and named blottin. It was previously unknown
      as a translated product. Blottin is also present in rat and human; the latter
      gene is also known as GDDR. The predicted full-length proteins are 184 amino
      acids long (20 kDa), reducing to 164 amino acids (18 kDa) after signal peptide
      cleavage. ISH of gastrointestinal tissues shows abundant blottin mRNA in gastric
      surface and foveolar epithelium. IHC shows cytoplasmic staining for blottin
      protein, and by immunoelectron microscopy in mucus granules and Golgi stacks.
      Previous work showed that blottin is down-regulated in gastric cancers. Blottin
      contains a BRICHOS domain, and has 56% similarity with gastrokine-1. Cultured HT
      29 cells express blottin and show increased DNA synthesis with antiblottin
      antibody; however, this effect is reversed by the immunising peptide. We have
      identified and characterised a TFF2-binding protein produced by gastric
      epithelium. Blottin may play a role in gastrointestinal mucosal protection and
      modulate gut epithelial cell proliferation.

PMID- 16888722
TI  - Proteomic analysis of Escherichia coli biofilms reveals the overexpression of the
      outer membrane protein OmpA.
AB  - Bacterial colonisation and biofilm formation on the surface of urinary catheters
      is a common cause of nosocomial infection, and as such is a major impediment to
      their long-term use. Understanding the mechanisms of biofilm formation on urinary
      catheters is critical to their control and will aid the future development of
      materials used in their manufacture. In this report we have used proteomic
      analysis coupled with immunoassays to show that the major outer membrane protein
      (OmpA) of Escherichia coli is overexpressed during biofilm formation. A series of
      synthetic hydrogels being developed for potential use as catheter coatings were
      used as the substrata and OmpA expression was increased in biofilms on all these
      surfaces, as well as being a feature of both a laboratory and a clinical strain
      of E. coli. Up-regulation of OmpA may, therefore, be a common feature of E. coli
      biofilms. These findings present OmpA as a potential target for biofilm
      inhibition and may contribute to the rational design of biofilm inhibiting
      hydrogel coatings for urinary catheters.

PMID- 16888723
TI  - Correlation of protein expression, Gleason score and DNA ploidy in prostate
      cancer.
AB  - The prognosis of prostate cancer correlates with tumor differentiation. Gleason
      score and DNA ploidy are two prognostic factors that correlate with prognosis. We
      analyzed differences in protein expression in prostate cancer of high and low
      aggressiveness according to these measures. From 35 prostatectomy specimens, 29
      cancer samples and 10 benign samples were harvested by scraping cells from cut
      surfaces. DNA ploidy was assessed by image cytometry. Protein preparations from
      cell suspensions were examined by 2-DE. Protein spots that differed
      quantitatively between sample groups were identified by MS fingerprinting of
      tryptic fragments and MS/MS sequence analysis. We found 39 protein spots with
      expression levels that were raised or lowered in correlation with Gleason score
      and/or DNA ploidy pattern (31 overexpressed in high-malignant cancer, 8
      underexpressed). Of these, 30 were identified by MS. Among overexpressed proteins
      were heat-shock, structural and membrane proteins and enzymes involved in gene
      silencing, protein synthesis/degradation, mitochondrial protein import (metaxin
      2), detoxification (GST-pi) and energy metabolism. Stroma-associated proteins
      were generally underexpressed. The protein expression of prostate cancer
      correlates with tumor differentiation. Potential prognostic markers may be found
      among proteins that are differentially expressed and the clinical value of these
      should be validated.

PMID- 16888724
TI  - Proteomic analysis of anti-angiogenic effects by a combined treatment with
      vinblastine and rapamycin in an endothelial cell line.
AB  - Angiogenesis controls the new blood supply routes into the tumor mass via the
      host endothelial cells (ECs). In this study, the EA.hy926 endothelial cell line
      has been treated with vinblastine (VBL) and rapamycin (RAP), both separately and
      in combination at low doses. Recently, we demonstrated the synergistic
      antiangiogenic effects of a combination of VBL and RAP at very low doses in vitro
      and in vivo. Herein, we confirm the ability of this combined treatment to
      statistically inhibit the proliferation of ECs, in a synergistic manner, by
      inducing apoptosis. The aim of this study was to substantiate these findings at
      the protein level. Differential proteomic analysis was performed on untreated
      control cells, treated with VBL, incubated with RAP, or subjected to a drug
      combination. Differentially expressed 113 polypeptide chains were visualized and
      65 were identified via MALDI-TOF analysis. Some of the regulated proteins are
      involved in the processes of angiogenesis, proliferation, migration, and
      apoptosis. The down-modulation of ATP synthase, annexin A2, heat shock p70,
      glucose-6-phosphate dehydrogenase, vasodilator-stimulated phosphoprotein,
      proteasome 26S, tryptophanyl-tRNA synthetase, and stathmin/OP18, as well as the
      up-modulation of carbonyl reductase, Rho-GDI, and histone H1.0 correlates with
      the synergistic antiangiogenic activity of VBL and RAP.

PMID- 16888727
TI  - Soft actuators based on liquid-crystalline elastomers.

PMID- 16888726
TI  - 18F-labeling of peptides by means of an organosilicon-based fluoride acceptor.

PMID- 16888728
TI  - Regioselectivity with hemispherical chelators: increasing the catalytic
      efficiency of complexes of diphosphanes with large bite angles.

PMID- 16888729
TI  - Double proton coupled charge transfer in DNA.

PMID- 16888730
TI  - A simple and powerful flow cytometric method for the simultaneous determination
      of multiple parameters at G protein-coupled receptor subtypes.
AB  - The quantification of pharmacological parameters at G protein-coupled receptors
      (GPCRs) is indispensable in drug research but costly and time-consuming when
      conventional methods are sequentially applied. With neuropeptide Y (NPY) Y(1),
      Y(2), and Y(5) receptors as model systems, a homogenous flow cytometric method
      for the simultaneous determination of the affinity, selectivity, and activity of
      GPCR ligands was developed. Mixtures of cells expressing the receptors of
      interest and cyanine-labeled NPY as a universal fluorescent Y(1), Y(2), and Y(5)
      receptor agonist were used. Calcium mobilization was measured in different
      channels with the aid of fluo-4 and fura red. A combination of dye-loaded HEL
      Y(1) and CHO-Y(2)-Galpha(qi5) cells with unloaded HEC-1B-Y(5) cells allowed the
      simultaneous determination of Y(1), Y(2), and Y(5) receptor selectivity preceded
      by the Y(1) and Y(2) receptor-mediated response with one and the same sample. The
      data are in good agreement with those determined by radioligand binding and
      spectrofluorimetry. The convenient, robust, and inexpensive multiparametric
      procedure offers a broad range of applications in the pharmacological
      characterization of GPCR ligands.

PMID- 16888731
TI  - Molecular basis of substrate recognition in D-3-hydroxybutyrate dehydrogenase
      from Pseudomonas putida.
AB  - D-3-Hydroxybutyrate dehydrogenase from Pseudomonas putida (EC 1.1.1.30) belongs
      to the family of short-chain dehydrogenases/reductases (SDRs). It catalyzes the
      reversible and stereospecific oxidation of D-3-hydroxybutyrate (D-3-HB) to
      acetoacetate with the aid of NAD(+) as coenzyme. This study contributes to
      understanding the mechanism and the high specificity of this enzyme towards its
      negatively charged and hydrophilic substrate. Sequence comparison of 44 bacterial
      HBDHs shows the residues Gln91, His141, Lys149, Lys192, and Gln193 to be strictly
      conserved. Site-directed mutagenesis of these amino acids to alanine and
      subsequent kinetic characterization of the mutated enzymes provides insight into
      the importance of these residues for substrate recognition and catalysis. Docking
      studies and molecular-dynamics simulations based on a three-dimensional structure
      model of a complex between P. putida HBDH and its coenzyme obtained by
      comparative molecular modeling were performed and provided deeper insight into
      the binding of the ligands at the molecular level. They show the residues Gln91,
      His141, Gln193, and, in particular, Lys149 to be involved in a hydrogen-bonding
      network with the carboxylate group of the substrate.

PMID- 16888732
TI  - Differential protein assembly on micropatterned surfaces with tailored molecular
      and surface multivalency.

PMID- 16888733
TI  - Silica pattern formation in diatoms: species-specific polyamine biosynthesis.
AB  - Diatoms are eukaryotic, unicellular algae that are well known for the intricate
      architecture of their silica-based cell walls. Species identification is mainly
      based on variations of their hierarchically organized silica structures.
      Particularly striking silica frameworks are found among diatoms that belong to
      the genus Coscinodiscus. Recent work indicates an important role for long-chain
      polyamines in guiding silica precipitation as well as in silica-pattern
      formation. Here we demonstrate that polyamines, even if isolated from closely
      related diatom species, exhibit substantial structural differences. Structural
      variations include the overall chain length, the degree of methylation, positions
      of secondary amino functionalities, and, unexpectedly, site-specific
      incorporation of a quaternary ammonium functionality. These findings support a
      specific role for polyamines in creating silica nanostructures.

PMID- 16888734
TI  - Catalysis and rational engineering of trans-acting pH6DZ1, an RNA-cleaving and
      fluorescence-signaling deoxyribozyme with a four-way junction structure.

PMID- 16888735
TI  - Bioassay labels based on apoferritin nanovehicles.

PMID- 16888736
TI  - Kinetic, thermodynamic, and mechanistic patterns for free (unbound) cytochrome c
      at Au/SAM junctions: impact of electronic coupling, hydrostatic pressure, and
      stabilizing/denaturing additives.
AB  - Combined kinetic (electrochemical) and thermodynamic (calorimetric)
      investigations were performed for an unbound (intact native-like) cytochrome c
      (CytC) freely diffusing to and from gold electrodes modified by hydroxyl
      terminated self-assembled monolayer films (SAMs), under a unique broad range of
      experimental conditions. Our approach included: 1) fine-tuning of the charge
      transfer (CT) distance by using the extended set of Au-deposited hydroxyl
      terminated alkanethiol SAMs [-S-(CH(2))(n)-OH] of variable thickness (n=2, 3, 4,
      6, 11); 2) application of a high-pressure (up to 150 MPa) kinetic strategy toward
      the representative Au/SAM/CytC assemblies (n=3, 4, 6); 3) complementary
      electrochemical and microcalorimetric studies on the impact of some stabilizing
      and denaturing additives. We report for the first time a mechanistic changeover
      detected for "free" CytC by three independent kinetic methods, manifested through
      1) the abrupt change in the dependence of the shape of the electron exchange
      standard rate constant (k(o)) versus the SAM thickness (resulting in a variation
      of estimated actual CT range within ca. 15 to 25 A including ca. 11 A of an
      "effective" heme-to-omega-hydroxyl distance). The corresponding values of the
      electronic coupling matrix element vary within the range from ca. 3 to 0.02 cm(
      1); 2) the change in activation volume from +6.7 (n=3), to approximately 0 (n=4),
      and -5.5 (n=6) cm(3) mol(-1) (disclosing at n=3 a direct pressure effect on the
      protein's internal viscosity); 3) a "full" Kramers-type viscosity dependence for
      k(o) at n=2 and 3 (demonstrating control of an intraglobular friction through the
      external dynamic properties), and its gradual transformation to the viscosity
      independent (nonadiabatic) regime at n=6 and 11. Multilateral cross-testing of
      "free" CytC in a native-like, glucose-stabilized and urea-destabilized (molten
      globule-like) states revealed novel intrinsic links between local/global
      structural and functional characteristics. Importantly, our results on the high
      pressure and solution-viscosity effects, together with matching literature data,
      strongly support the concept of "dynamic slaving", which implies that
      fluctuations involving "small" solution components control the proteins'
      intrinsic dynamics and function in a highly cooperative manner as far as CT
      processes under adiabatic conditions are concerned.

PMID- 16888737
TI  - Acid-base and metal-ion-binding properties of xanthosine 5'-monophosphate (XMP)
      in aqueous solution: complex stabilities, isomeric equilibria, and extent of
      macrochelation.
AB  - The four acidity constants of threefold protonated xanthosine 5'-monophosphate,
      H3(XMP)+, reveal that at the physiological pH of 7.5 (XMP-H)(3-) strongly
      dominates (and not XMP(2-) as given in textbooks); this is in contrast to the
      related inosine (IMP(2-)) and guanosine 5'-monophosphate (GMP(2-)) and it means
      that XMP should better be named as xanthosinate 5'-monophosphate. In addition,
      evidence is provided for a tautomeric (XMP-HN1)(3-)/(XMP-HN3)(3-) equilibrium.
      The stability constants of the M(H;XMP)+ species were estimated and those of the
      M(XMP) and M(XMP-H)- complexes (M2+=Mg2+, Ca2+, Sr2+, Ba2+, Mn2+, Co2+, Ni2+,
      Cu2+, Zn2+, Cd2+) measured potentiometrically in aqueous solution. The primary
      M2+ binding site in M(XMP) is (mostly) N7 of the monodeprotonated xanthine
      residue, the proton being at the phosphate group. The corresponding macrochelates
      involving P(O)2(OH)- (most likely outer-sphere) are formed to approximately 65%
      for nearly all M2+. In M(XMP-H)- the primary M2+ binding site is (mostly) the
      phosphate group; here the formation degree of the N7 macrochelates varies widely
      from close to zero for the alkaline earth ions, to approximately 50% for Mn2+,
      and approximately 90% or more for Co2+, Ni2+, Cu2+, Zn2+, and Cd2+. Because for
      (XMP-H)(3-) the micro stability constants quantifying the M2+ affinity of the
      xanthosinate and PO3(2-) residues are known, one may apply a recently developed
      quantification method for the chelate effect to the corresponding macrochelates;
      this chelate effect is close to zero for the alkaline earth ions and it amounts
      to about one log unit for Co2+, Ni2+, Cu2+. This method also allows calculation
      of the formation degrees of the monodentatally coordinated isomers; this
      information is of relevance for biological systems because it demonstrates how
      metal ions can switch from one site to another through macrochelate formation.
      These insights are meaningful for metal-ion-dependent reactions of XMP in
      metabolic pathways; previous mechanistic proposals based on XMP(2-) need
      revision.

PMID- 16888739
TI  - A new basic motif in cyanometallate coordination polymers: structure and magnetic
      behavior of M(mu-OH2)2[Au(CN)2]2 (M=Cu, Ni).
AB  - The structures of two cyanoaurate-based coordination polymers, M(mu
      OH(2))(2)[Au(CN)(2)](2) (M=Cu, Ni), were determined by using a combination of
      powder and single-crystal X-ray diffraction techniques. The basic structural
      motif for both polymers contains rarely observed M(mu-OH(2))(2)M double aqua
      bridges, which generate an infinite chain; two trans [Au(CN)(2)](-) units also
      dangle from each metal center. The chains form ribbons that interact three
      dimensionally through CNH hydrogen bonding. The magnetic properties of both
      compounds and of the dehydrated analogue Cu[Au(CN)(2)](2) were investigated by
      direct current (dc) and alternating current (ac) magnetometry; muon spin
      relaxation data was also obtained to probe their magnetic properties in zero
      field. In M(mu-OH(2))(2)[Au(CN)(2)](2), ferromagnetic chains of M(mu-OH(2))(2)M
      are present below 20 K. Interchain magnetic interactions mediated through
      hydrogen bonding, involving water and cyanoaurate units, yield a long-range
      magnetically ordered system in Cu(mu-OH(2))(2)[Au(CN)(2)](2) below 0.20 K, as
      indicated by precession in the muon spin polarization decay. Ni(mu
      OH(2))(2)[Au(CN)(2)](2) undergoes a transition to a spin-glass state in zero
      field at 3.6 K, as indicated by a combination of muon spin-relaxation and ac
      susceptibility data. This transition is probably due to competing interactions
      that lead to spin frustration. A phase transition to a paramagnetic state is
      possible for Ni(mu-OH(2))(2)[Au(CN)(2)](2) upon application of an external field;
      the critical field was determined to be 700 Oe at 1.8 K. The dehydrated compound
      Cu[Au(CN)(2)](2) shows weak antiferromagnetic interactions at low temperatures.

PMID- 16888740
TI  - Investigation of a molecular morphology effect on polyphenylazomethine
      dendrimers; physical properties and metal-assembling processes.
AB  - A series of novel dendritic polyphenylazomethines (DPA) with asymmetric
      morphologies was synthesized. Their physical properties, such as encapsulating
      effect, molecular dynamics, and metal assembly, are strongly dependent on the
      entire conformation of the molecules. The most important property is layer-by
      layer metal assembly in the dendrimer structure from the core to the outside. Bis
      and tris-substituted DPAs of the fourth generation also act as frameworks for
      stepwise assembly of a metal component (SnCl2), like the fully substituted
      symmetric DPA. However, extensive investigation of metal assembly in specific
      DPAs revealed that they do not follow the stepwise process. The molecular density
      calculated from the experimental hydrodynamic volume indicated that bis- and tris
      substituted DPAs with asymmetric morphology still retain a free space similar to
      that of fully substituted symmetric DPA. The monosubstituted DPA, however,
      displayed a slightly higher density (smaller space) than the other DPAs. The
      experimental results suggest a bent conformation of the dendrimer in which the
      core moiety is folded into the dendron structure. In addition, the molecular
      dynamics were probed by means of the 1H NMR signals of the porphyrin core. It was
      demonstrated that the conformation is not fixed at room temperature in solvated
      DPAs, especially in monosubstituted DPA. A similar observation was for the
      smaller DPAs (third generations) with asymmetric morphologies. These dendrimers
      do not follow the stepwise complexation process. The structures of bis- and tris
      substituted dendrimers which accurately follow the stepwise process are fixed.
      These observations provide a new insight into the finely controlled metal
      assembly chemistry of dendritic macromolecules, and a rigid and fixed
      conformation is one of important factors for their unique properties.

PMID- 16888738
TI  - Syntheses, photophysical properties, and application of through-bond energy
      transfer cassettes for biotechnology.
AB  - We have designed fluorescent "through-bond energy-transfer cassettes" that can
      harvest energy of a relatively short wavelength (e.g., 490 nm), and emit it at
      appreciably longer wavelengths without significant loss of intensity. Probes of
      this type could be particularly useful in biotechnology for multiplexing
      experiments in which several different outputs are to be observed from a single
      excitation source. Cassettes 1-4 were designed, prepared, and studied as model
      systems to achieve this end. They were synthesized through convergent routes that
      feature coupling of specially prepared fluorescein- and rhodamine-derived
      fragments. The four cassettes were shown to emit strongly, with highly efficient
      energy transfer. Their emission maxima cover a broad range of wavelengths
      (broader than the four dye cassettes currently used for most high-throughput DNA
      sequencing), and they exhibit faster energy-transfer rates than a similar through
      space energy-transfer cassette. Specifically, energy-transfer rates in these
      cassettes is around 6-7 ps, in contrast to a similar through-space energy
      transfer system shown to have a decay time of around 35 ps. Moreover, the
      cassettes are considerably more stable to photobleaching than fluorescein, even
      though they each contain fluorescein-derived donors. This was confirmed by bulk
      fluorescent measurements, and in single-molecule-detection studies. Modification
      of a commercial automated DNA-sequencing apparatus to detect the emissions of
      these four energy-transfer cassettes enabled single-color dye-primer sequencing.

PMID- 16888741
TI  - Bleomycin is a potent small-molecule inhibitor of hepatitis C virus replication.

PMID- 16888742
TI  - Nanoswitches based on DNA base pairs: why adenine-thymine is less suitable than
      guanine-cytosine.
AB  - Substituted Watson-Crick guanine-cytosine (GC) base pairs were recently shown to
      yield robust three-state nanoswitches. Here, we address the question: Can such
      supramolecular switches also be based on Watson-Crick adenine-thymine (AT) base
      pairs? We have theoretically analyzed AT pairs in which purine-C8 and/or
      pyrimidine-C6 positions carry a substituent X=NH(-), NH(2), NH(3) (+) (N series),
      O(-), OH or OH(2) (+) (O series), using the generalized gradient approximation
      (GGA) of density functional theory at the BP86/TZ2P level. Thus, we explore the
      trend in geometrical shape and hydrogen bond strengths in AT pairs along a series
      of stepwise protonations of the substituents. Introducing a charge on the
      substituents leads to substantial and characteristic changes in the individual
      hydrogen bond lengths when compared to the neutral AT pair. However, the trends
      along the series of negative, neutral, and positive substituents are less
      systematic and less pronounced than for GC. In certain instances, internal proton
      transfer from thymine to adenine occurs. Our results suggest that AT is a less
      suitable candidate than GC in the quest for chemically controlled nanoswitches.

PMID- 16888743
TI  - Dissociating the past from the present in the activity of place cells.
AB  - It has been proposed that declarative memories can be dependent on both an
      episodic and a semantic memory system. While the semantic system deals with
      factual information devoid of reference to its acquisition, the episodic system,
      characterized by mental time travel, deals with the unique past experience in
      which an event took place. Episodic memory is characteristically hippocampus
      dependent. Place cells are recorded from the hippocampus of rodents and their
      firing reflects many of the key characteristics of episodic memory. For example,
      they encode information about "what" happens "where," as well as temporal
      information. However, when these features are expressed during an animal's
      behavior, the neuronal activity could merely be categorizing the present
      situation and could therefore reflect semantic memory rather than episodic
      memory. We propose that mental time travel is the key feature of episodic memory
      and that it should take a form, in the awake animal, similar to the replay of
      behavioral patterns of activity that has been observed in hippocampus during
      sleep. Using tasks designed to evoke episodic memory, one should be able to see
      memory reactivation of behaviorally relevant sequences of activity in the awake
      animal while recording from hippocampus and other cortical structures.

PMID- 16888744
TI  - Fast rate coding in hippocampal CA3 cell ensembles.
AB  - Environments with overlapping features are represented by distinct patterns of
      activity in the hippocampus, enabling information to be stored and retrieved with
      minimal interference. This orthogonalization of correlated inputs is thought to
      take place within the hippocampus itself. However, the orthogonalization process
      has been shown to take days to develop in CA1. This prolonged time course is in
      striking contrast to the fast encoding of behavioral memory by the hippocampus.
      To explore this apparent paradox, we asked whether orthogonalization depended on
      the type of remapping exhibited by the hippocampal network. We have previously
      distinguished two types of remapping, global remapping, which results in the
      activation of different assemblies of place fields, and rate remapping, which
      encodes differences between cue constellations by substantial changes in firing
      rate without a change in the place code. Global remapping has previously been
      shown to be expressed immediately at novel locations. Here we asked if rate
      remapping follows a slower time course. Ensemble activity was recorded
      simultaneously from CA3 and CA1 in rats exposed to two similar, novel
      environments. It was found that rate changes in response to novel sensory cue
      configurations can form immediately, just as during global remapping, in
      particular in CA3. The fast encoding of both spatial and nonspatial information
      in CA3 is consistent with a role for the autoassociative CA3 circuitry in the
      acquisition and expression of episodic memories.

PMID- 16888746
TI  - One hundred years of light quanta (Nobel lecture).

PMID- 16888745
TI  - Tandem mass spectra of ammonium adducts of monosaccharides: differentiation of
      diastereomers.
AB  - Tandem mass spectra of ammonium adducts of monosaccharides gave characteristic
      fragmentation patterns involving elimination of NH3/H2O followed by multiple
      eliminations of H2O and cross ring cleavages. Tandem mass spectra were examined
      over a range of collision energies (1-20 eV) on a triple-quadrupole mass
      spectrometer. The breakdown behavior of the ammonium adducts revealed patterns
      that could differentiate diastereomers of monosaccharides.

PMID- 16888747
TI  - Vibrational structure of endohedral fullerene Sc3N@C78 (D3h'): evidence for a
      strong coupling between the Sc3N cluster and C78 cage.
AB  - The vibrational structure of the endohedral cluster fullerene Sc(3)N@C(78) is
      studied by FTIR spectroscopy, Raman spectroscopy and DFT-based quantum chemical
      calculations. Remarkably good agreement between experimental and calculated
      spectra is achieved and a full assignment of the Sc(3)N-based vibrational modes
      is given. Significant differences in the vibrational structure of the endohedral
      cluster fullerene Sc(3)N@C(78) and the empty, charged C(78) (6-): 5 (D(3h)') are
      rationalized by the strong coupling between the Sc(3)N cluster and the fullerene
      cage. This coupling has its origin in a significant overlap of the Sc(3)N and
      C(78) molecular orbitals, and causes atomic-charge and bond-length
      redistributions compared to the neutral C(78) and the C(78) (6-) anion. An ionic
      model is not sufficient to describe the electronic, geometric and vibrational
      structure of the Sc(3)N@C(78) nitride cluster fullerene.

PMID- 16888748
TI  - Theoretical dynamic studies on the reaction of CH3C(O)CH3-nFn with the hydroxyl
      radical and the chlorine atom.
AB  - The mechanisms of the reactions: CH(3)C(O)CH(2)F+OH/Cl-->products (R1/R2) and
      CH(3)C(O)CF(3)+OH/Cl-->products (R3/R4) are studied over a wide temperature range
      (200-2000 K) by means of the dual-level direct dynamics method. The optimized
      geometries and frequencies of the stationary points are calculated at the MP2/cc
      pVDZ and B3LYP/6-311G(d,p) levels. The energy profiles of the reactions are then
      refined with the interpolated single-point-energy method (ISPE) at the BMC-CCSD
      level. The canonical variational transition-state theory (CVT) with the small
      curvature-tunneling (SCT) correction method is used to calculate the rate
      constants. Using group-balanced isodesmic reactions as working chemical
      reactions, the standard enthalpies of formation for CH(3)C(O)CH(2)F,
      CH(3)C(O)CF(3), CH(3)C(O)CHF, CH(2)C(O)CH(2)F, and CH(2)C(O)CF(3) are evaluated
      at the CCSD(T)/6-311+G(2d,p)//MP2/cc-pVDZ level of theory. The results indicate
      that the hydrogen abstraction is dominated by removal from the fluoromethyl
      position rather than from the methyl position.

PMID- 16888749
TI  - New developments in natural products-based anti-AIDS research.
AB  - This review discusses anti-HIV natural products from several compound classes,
      including terpenoids, coumarins, alkaloids, polyphenols, tannins, and flavonoids.
      Natural products can provide novel anti-AIDS chemotherapeutic leads that are
      structurally unique or have new mechanisms of action. The drug discovery and
      development process proceeds from bioactivity-directed isolation and
      identification of a promising lead natural product, followed by rational design
      based structural modification and structure-activity relationship analyses to
      optimize the lead compound as a drug candidate. This process is notably
      exemplified by the discovery of the modified betulinic acid derivative, DSB [PA
      457], which is currently in Phase II clinical trial and is the first-in-class HIV
      maturation inhibitor (MI).

PMID- 16888750
TI  - A theoretical study of the mechanism and kinetics of F+N3 reactions.
AB  - Both the singlet(1A') and triplet(3A'') potential energy surfaces (PESs) of
      F+N(3) reactions are investigated using the complete-active-space self-consistent
      field (CASSCF) and the multireference configuration interaction (MRCI) methods
      with a proper active space. The minimum energy crossing point (MECP) at the
      intersection seam between the 1A' and 3A'' PESs is located and used to clarify
      the reaction mechanisms. Two triplet transition states are found, with one in the
      cis form and the other one in the trans form. Further kinetic calculations are
      performed with the canonical unified statistical (CUS) theory on the singlet PES
      and the improved canonical variational transition-state (ICVT) method on the
      triplet PES. The rate constants are also reported. At 298 K, the calculated rate
      constant is in reasonably good agreement with experimental values, and spin-orbit
      coupling effects lower it by 28 %. The spectroscopic constants derived from the
      fitted potential-energy curves for the singlet and triplet states of NF are in
      very good agreement with experimental values. Our calculations indicate that the
      adiabatic reaction on the singlet PES leading to NF(a(1)Delta)+N(2) is the major
      channel, whereas the nonadiabatic reaction through the MECP, which leads to
      NF(X(3)Sigma(-))+N(2), is a minor channel.

PMID- 16888751
TI  - New developments in the chemistry and biology of the bioactive constituents of
      Tanshen.
AB  - Tanshen, the rhizome of Salvia miltiorrhiza Bunge, has been used in Chinese
      traditional medicine (TCM) for multiple therapeutic remedies. The major
      constituents of Tanshen include water-soluble phenolic acids and lipophilic
      tanshinones. Phenolic acids possess antioxidant and anticoagulant activities,
      whereas tanshinones show antibacterial, antioxidant, and antineoplastic
      activities. This review will focus on recent developments concerning the chemical
      constituents of Tanshen and their biological activities. These chemical and
      biological studies continue to increase our understanding about a scientific
      basis for the traditional clinical use of Tanshen and can also contribute to the
      development of new drug candidates. Recently, in the author's laboratory, a new
      compound, neo-tanshinlactone, was discovered to have potent selective antibreast
      cancer activity. This compound might serve as a lead for developing promising
      antibreast cancer clinical trials candidates.

PMID- 16888752
TI  - Mass spectrometric characterization of covalent modification of human serum
      albumin by 4-hydroxy-trans-2-nonenal.
AB  - Several pieces of evidence indicate that albumin modified by HNE is a promising
      biomarker of systemic oxidative stress and that HNE-modified albumin may
      contribute to the immune reactions triggered by lipid peroxidation-derived
      antigens. In this study, we found by HPLC analysis that HNE is rapidly quenched
      by human serum albumin (HSA) because of the covalent adduction to the different
      accessible nucleophilic residues of the protein, as demonstrated by electrospray
      ionization mass spectrometry (ESI-MS) direct infusion experiments (one to nine
      HNE adducts, depending on the molar ratio used, from 1:0.25 to 1:5 HSA:HNE). An
      LC-ESI-MS/MS approach was then applied to enzymatically digested HNE-modified
      albumin, which permitted the identification of 11 different HNE adducts, 8
      Michael adducts (MA) and 3 Schiff bases (SB), involving nine nucleophilic sites,
      namely: His67 (MA), His146 (MA), His242 (MA), His288 (MA), His510 (MA), Lys 195
      (SB), Lys 199 (MA, SB), Lys525 (MA, SB) and Cys34 (MA). The most reactive HNE
      adduction site was found to be Cys34 (MA) followed by Lys199, which primarily
      reacts through the formation of a Schiff base, and His146, giving the
      corresponding HNE Michael adduct. These albumin modifications are suitable tags
      of HNE-adducted albumin and could be useful biomarkers of oxidative and
      carbonylation damage in humans.

PMID- 16888753
TI  - The effects of expanding patient choice of provider on waiting times: evidence
      from a policy experiment.
AB  - Long waiting times for inpatient treatment in the UK National Health Service have
      been a source of popular and political concern, and therefore a target for policy
      initiatives. In the London Patient Choice Project, patients at risk of breaching
      inpatient waiting time targets were offered the choice of an alternative hospital
      with a guaranteed shorter wait. This paper develops a simple theoretical model of
      the effect of greater patient choice on waiting times. It then uses a difference
      in difference econometric methodology to estimate the impact of the London choice
      project on ophthalmology waiting times. In line with the model predictions, the
      project led to shorter average waiting times in the London region and a
      convergence in waiting times amongst London hospitals.

PMID- 16888754
TI  - Ambient Eberlin reactions via desorption electrospray ionization mass
      spectrometry.

PMID- 16888756
TI  - Can anti-migratory drugs be screened in vitro? A review of 2D and 3D assays for
      the quantitative analysis of cell migration.
AB  - The aim of the present review is to detail and analyze the pros and cons of in
      vitro tests available to quantify the anti-migratory effects of anti-cancer drugs
      for their eventual use in combating the dispersal of tumor cells, a clinical need
      which currently remains unsatisfied. We therefore briefly sum up why anti
      migratory drugs constitute a promising approach in oncology while at the same
      time emphasizing that migrating cancer cells are resistant to apoptosis. To
      analyze the pros and cons of the various in vitro tests under review we also
      briefly sum up the molecular and cellular stages of cancer cell migration, an
      approach that enables us to argue both that no single in vitro test is sufficient
      to characterize the anti-migratory potential of a drug and that standardization
      is needed for the efficient quantitative analysis of cell locomotion in a 3D
      environment. Before concluding our review we devote the final two parts (i) to
      the description of new prototypes which, in the near future, could enter the
      screening process with a view to identifying novel anti-migratory compounds, and
      (ii) to the anti-migratory compounds currently developed against cancer, with
      particular emphasis on how these compounds were selected before entering the
      clinical trial phase.

PMID- 16888757
TI  - Evaluation of the integrated cognitive model of depression and its specificity in
      a migrant population.
AB  - This study empirically tested the specificity of the integrated cognitive model
      (ICM) of depression, which postulates that negative life events interact with
      dysfunctional attitudes to increase the frequency and severity of automatic
      thoughts, subsequently affecting depressive symptoms. We also examined the three
      competing models: the linear mediation model, the alternative etiologies model,
      and the symptom model. We anticipated that we might examine these models more
      appropriately using data from a population at an increased risk of developing
      depressive symptoms. As such, two-wave panel data were obtained from a group of
      107 Korean migrants who had been in Australia less than 1 year. Structural
      equation modeling revealed that the ICM provided an adequate and much better fit
      than the three competing models. The ICM was also found to support the cognitive
      specificity theory of depression and anxiety. These findings suggest that
      dysfunctional attitudes can be a common cognitive moderator of depression and
      anxiety, whereas automatic thoughts and anxious self-statements can be specific
      cognitive mediators of anxiety and depression, respectively.

PMID- 16888758
TI  - Mass spectrometry in sports drug testing: Structure characterization and
      analytical assays.
AB  - Owing to the sensitive, selective, and unambiguous nature of mass spectrometric
      analyses, chromatographic techniques interfaced to various kinds of mass
      spectrometers have become the most frequently employed strategy in the fight
      against doping. To obtain utmost confidence in analytical assays, mass
      spectrometric characterization of target analytes and typical dissociation
      pathways have been utilized as basis for the development of reliable and robust
      screening as well as confirmation procedures. Methods for qualitative and/or
      quantitative determinations of prohibited low and high molecular weight drugs
      have been established in doping control laboratories preferably employing gas or
      liquid chromatography combined with electron, chemical, or atmospheric pressure
      ionization followed by analyses using quadrupole, ion trap, linear ion trap, or
      hyphenated techniques. The versatility of modern mass spectrometers enable
      specific as well as comprehensive measurements allowing sports drug testing
      laboratories to determine the misuse of therapeutics such as anabolic-androgenic
      steroids, stimulants, masking agents or so-called designer drugs in athletes'
      blood or urine specimens, and a selection of recent developments is summarized in
      this review.

PMID- 16888761
TI  - Vinorelbine, doxorubicin, and prednisone in androgen-independent prostate cancer.
AB  - BACKGROUND: Ultimately, patients with metastatic prostate cancer progress on
      androgen ablation therapy. The investigation of new chemotherapeutic regimens for
      the treatment of androgen-independent prostate cancer (AIPC) is essential. The
      authors conducted a Phase II trial with vinorelbine, doxorubicin, and daily
      prednisone (NAP) to investigate the antitumor activity and palliative response of
      this regimen in patients with AIPC. METHODS: Forty-six patients entered this
      Phase II combination chemotherapy trial. Patients were treated with both
      vinorelbine and doxorubicin at doses of 20 mg/m2 on Days 1, 8, and 15 every 28
      days and prednisone 5 mg twice daily. Endpoints included prostate-specific
      antigen (PSA) response and palliation, as measured by the Functional Assessment
      of Cancer Therapy-Prostate (FACT-P) instrument, the Brief Pain Inventory Scale,
      and a narcotic analgesic log. RESULTS: The median follow-up for all 46 patients
      was 13.4 months. Fifty-two percent of patients had impaired performance status at
      baseline. One responding patient remained on NAP and was progression-free at 11.5
      months. Thirty-nine patients progressed, 3 patients died prior to response
      assessment, and 3 patients refused therapy. The median overall survival was 57
      weeks (95% confidence interval [95% CI], 36-76 weeks), and the median time to
      disease progression was 17 weeks (range, 11-24 weeks). The PSA response among the
      36 patients who completed 3 cycles of NAP was 42% (95% CI, 26-59%). There was a
      statistically significant improvement in quality of life measured both by the
      FACT-General instrument (P = .03) and the FACT-P instrument (P = .0006) over the
      3 months compared with baseline measurements. Pain medicine use also improved:
      The median morphine equivalents among patients who were taking pain medications
      at the time of study enrollment showed a substantial decline after 1 cycle of
      treatment that was maintained. Pain (as assessed by the Brief Pain Inventory)
      improved compared with baseline pain at the 2nd-month assessment (worst pain, P =
      .08; least pain, P = .02; and average pain, P = .003). Overall, the regimen was
      tolerated well. The most common side effects were mild fatigue and
      gastrointestinal complaints (all of which were Grade 1 or 2 [according to Version
      2.0 of the Expanded Common Toxicity Criteria]). Seventeen patients (37%)
      experienced Grade 3 or 4 neutropenia. Five patients (11%) developed a cardiac
      ejection fraction of <50% during treatment and had doxorubicin discontinued. No
      patients developed clinical congestive heart failure. CONCLUSIONS: The NAP
      combination produced substantive palliation and a moderate response rate in men
      with AIPC.

PMID- 16888762
TI  - Gel-free mass spectrometry-based high throughput proteomics: tools for studying
      biological response of proteins and proteomes.
AB  - Revolutionary advances in biological mass spectrometry (MS) have provided a basic
      tool to make possible comprehensive proteomic analysis. Traditionally, two
      dimensional gel electrophoresis has been used as a separation method coupled with
      MS to facilitate analysis of complex protein mixtures. Despite the utility of
      this method, the many challenges of comprehensive proteomic analysis has
      motivated the development of gel-free MS-based strategies to obtain information
      not accessible using two-dimensional gel separations. These advanced strategies
      have enabled researchers to dig deeper into complex proteomes, gaining insights
      into the composition, quantitative response, covalent modifications and
      macromolecular interactions of proteins that collectively drive cellular
      function. This review describes the current state of gel-free, high throughput
      proteomic strategies using MS, including (i) the separation approaches commonly
      used for complex mixture analysis; (ii) strategies for large-scale quantitative
      analysis; (iii) analysis of post-translational modifications; and (iv) recent
      advances and future directions. The use of these strategies to make new
      discoveries at the proteome level into the effects of disease or other cellular
      perturbations is discussed in a variety of contexts, providing information on the
      potential of these tools in electromagnetic field research.

PMID- 16888763
TI  - Proteome modifications of the medicinal leech nervous system under bacterial
      challenge.
AB  - Once considered as lacking intrinsic immune mechanisms, the CNS of vertebrates is
      now known to be capable of mounting its own innate immune response.
      Interestingly, while invertebrates have been very useful in the interpretation of
      general vertebrate innate immunity mechanisms, only scarce data are available on
      the immune response of nervous tissue within this group. This study provides new
      data on the innate immune response of medicinal leech Hirudo medicinalis CNS. We
      identified several spots in 2-D gels of leech CNS proteins that showed specific
      changes following bacterial challenge, thus demonstrating the ability of the
      leech nervous system to mount a response to an immune stress. Protein
      identifications were based on comparison of sequence data with publicly available
      databases and a recently established leech ESTs database. The broad nature of the
      identified proteins suggests a clear involvement of cytoskeletal rearrangements,
      endoplasmic reticulum stress, modulation of synaptic activity and calcium
      mobilization, all during the first 24 hours of this response. Moreover, several
      of these proteins are specifically expressed in glial cells, suggesting an
      important role for glial cells in the immune response of the leech nervous
      system, similar to what has been observed in vertebrates.

PMID- 16888764
TI  - Toward a comprehensive quantitative proteome database: protein expression map of
      lymphoid neoplasms by 2-D DIGE and MS.
AB  - Using 2-D DIGE, we constructed a quantitative 2-D database including 309 proteins
      corresponding to 389 protein spots across 42 lymphoid neoplasm cell lines. The
      proteins separated by 2-D PAGE were identified by MS and assigned to the
      expression data obtained by 2-D DIGE. The cell lines were categorized into four
      groups: those from Hodgkin's lymphoma (HL) (4 cell lines), B cell malignancies
      (19 cell lines), T cell malignancies (16 cell lines), and natural killer (NK)
      cell malignancies (3 cell lines). We characterized the proteins in the database
      by classifying them according to their expression level. We found 28 proteins
      with more than a 2-fold difference between the cell line groups. We also noted
      the proteins that allowed multidimensional separation to be achieved (1) between
      HL cells and other cells, (2) between the cells derived from B cells, T cells and
      NK cells, and (3) between HL cells and anaplastic large cell lymphoma cells.
      Decision tree classification identified five proteins that could be used to
      classify the 42 cell lines according to differentiation. These results suggest
      that the quantitative 2-D database using 2-D DIGE will be a useful resource for
      studying the mechanisms underlying the differentiation phenotypes of lymphoid
      neoplasms.

PMID- 16888765
TI  - Metabolomics: current technologies and future trends.
AB  - The ability to sequence whole genomes has taught us that our knowledge with
      respect to gene function is rather limited with typically 30-40% of open reading
      frames having no known function. Thus, within the life sciences there is a need
      for determination of the biological function of these so-called orphan genes,
      some of which may be molecular targets for therapeutic intervention. The search
      for specific mRNA, proteins, or metabolites that can serve as diagnostic markers
      has also increased, as has the fact that these biomarkers may be useful in
      following and predicting disease progression or response to therapy. Functional
      analyses have become increasingly popular. They include investigations at the
      level of gene expression (transcriptomics), protein translation (proteomics) and
      more recently the metabolite network (metabolomics). This article provides an
      overview of metabolomics and discusses its complementary role with
      transcriptomics and proteomics, and within system biology. It highlights how
      metabolome analyses are conducted and how the highly complex data that are
      generated are analysed. Non-invasive footprinting analysis is also discussed as
      this has many applications to in vitro cell systems. Finally, for studying biotic
      or abiotic stresses on animals, plants or microbes, we believe that metabolomics
      could very easily be applied to large populations, because this approach tends to
      be of higher throughput and generally lower cost than transcriptomics and
      proteomics, whilst also providing indications of which area of metabolism may be
      affected by external perturbation.

PMID- 16888767
TI  - Effects of global system for mobile communications 1800 MHz radiofrequency
      electromagnetic fields on gene and protein expression in MCF-7 cells.
AB  - Despite many studies over a decade, it still remains ambiguous as to the real
      biological effects induced by radiofrequency electromagnetic fields (RF EMF)
      utilized in mobile telephony. Here we investigated global gene and protein
      responses to RF EMF simulating the Global System for Mobile Communications (GSM)
      1800 MHz signal in human breast cancer cell line MCF-7 using genomic and
      proteomic approaches. GeneChip analysis identified a handful of consistent
      changed genes after exposure to RF EMF at specific absorption rates (SAR) of up
      to 3.5 W/kg for 24 h. However, these differentially transcribed genes could not
      be further confirmed by real-time RT-PCR assay. Meanwhile, systematic proteome
      analysis of the MCF-7 cells revealed that a few but different proteins were
      differentially expressed under continuous or intermittent RF EMF exposure at SAR
      of 3.5 W/kg for 24 h or less, implying that the observed effects might have
      occurred by chance. Overall, the present study does not provide convincing
      evidence that RF EMF exposure under current experimental conditions can produce
      distinct effects on gene and protein expression in the MCF-7 cells.

PMID- 16888766
TI  - The discovery of labile methyl esters on proliferating cell nuclear antigen by
      MS/MS.
AB  - The post-translational modification of proliferating cell nuclear antigen (PCNA)
      has been implicated in modulating its function for over 20 years. With multiple
      interacting partners, PCNA is involved in processes ranging from DNA replication
      and repair to cell cycle control and apoptosis. The ability of PCNA to
      distinguish between specific binding partners in different tasks is currently of
      intense interest, and several post-translational modifications have been reported
      to modulate its function. Unfortunately, these reports have produced
      contradictory information on the type(s) of modification present on the molecule.
      Here we report a detailed structural analysis of a single acidic PCNA isoform,
      cancer-specific polyferating nuclear anitgen (csPCNA), isolated from breast
      cancer cells by 2D-PAGE and LC-MS/MS. With this approach we fully characterized
      the csPCNA isoform and confidently identified a single post-translational
      modification, methyl esterification. Interestingly, the methyl esters
      consistently localized to 15 specific glutamic and aspartic acid residues of
      csPCNA. The methyl esterification of csPCNA represents a novel type of post
      translational modification in mammalian cells that could ultimately hold the key
      towards unlocking its diverse functions.

PMID- 16888768
TI  - Questions and answers concerning applicability of proteomics and transcriptomics
      in EMF research.
AB  - The applicability of high-throughput screening techniques of transcriptomics,
      proteomics and metabolomics in the search for biological and health effects of
      electromagnetic fields is a hotly debated issue. On the one hand, use of these
      modern screening technologies speeds up the discovery process and gives broader
      insight into biochemical events that follow the exposure to electromagnetic
      fields. On the other hand these modern screening technologies have the problem of
      reproducibility and variability between experiments and are prone to produce
      false positive results. These and other issues concerning the applicability of
      modern screening technologies were the topic of a workshop held at STUK in 2005
      (30 October to 1 November) in Helsinki, Finland, and this Report summarizes the
      discussions at this workshop.

PMID- 16888769
TI  - High intensity solid-state UV source for time-gated luminescence microscopy.
AB  - BACKGROUND: The unique discriminative ability of immunofluorescent probes can be
      severely compromised when probe emission competes against naturally occurring,
      intrinsically fluorescent substances (autofluorophores). Luminescence microscopes
      that operate in the time-domain can selectively resolve probes with long
      fluorescence lifetimes (tau > 100 micros) against short-lived fluorescence to
      deliver greatly improved signal-to-noise ratio (SNR). A novel time-gated
      luminescence microscope design is reported that employs an ultraviolet (UV) light
      emitting diode (LED) to excite fluorescence from a europium chelate
      immunoconjugate with a long fluorescence lifetime. METHODS: A commercial Zeiss
      epifluorescence microscope was adapted for TGL operation by fitting with a time
      gated image-intensified CCD camera and a high-power (100 mW) UV LED. Capture of
      the luminescence was delayed for a precise interval following excitation so that
      autofluorescence was suppressed. Giardia cysts were labeled in situ with antibody
      conjugated to a europium chelate (BHHST) with a fluorescence lifetime >500
      micros. RESULTS: BHHST-labeled Giardia cysts emit at 617 nm when excited in the
      UV and were difficult to locate within the matrix of fluorescent algae using
      conventional fluorescence microscopy, and the SNR of probe to autofluorescent
      background was 0.51:1. However in time-gated luminescence mode with a gate-delay
      of 5 mus, the SNR was improved to 12.8:1, a 25-fold improvement. CONCLUSION: In
      comparison to xenon flashlamps, UV LEDs are inexpensive, easily powered, and
      extinguish quickly. Furthermore, the spiked emission of the LED enabled removal
      of spectral filters from the microscope to significantly improve efficiency of
      fluorescence excitation and capture.

PMID- 16888770
TI  - Quantitative linear unmixing of CFP and YFP from spectral images acquired with
      two-photon excitation.
AB  - BACKGROUND: Spectrally distinct fluorescent proteins (FPs) have been developed
      permitting the visualization of several proteins simultaneously in living cells.
      The emission spectra of FPs, in most cases, overlap, making signal separation
      based on filter technology inefficient and in cases of bleed-through, inaccurate.
      Spectral imaging can overcome these obstacles through a process called linear
      unmixing. Given a complex spectra composed of multiple fluorophores, linear
      unmixing can reduce the complex signal to its individual, weighted, component
      spectra. Spectral imaging with two-photon excitation allows the collection of
      nontruncated emission spectra. The accuracy of linear unmixing under these
      conditions needs to be evaluated. METHODS: Capillaries containing defined
      mixtures of CFP and YFP were used to test the accuracy of linear unmixing using
      spectral images obtained with two-photon excitation. RESULTS: Linear unmixing can
      be accurate when wavelength and power-matched reference spectra are provided to
      the algorithm. Linear unmixing errors can occur due to (1) excitation laser
      contamination of emission signals, (2) the presence of FRET, (3) poor selection
      of excitation wavelength, and (4) failure to background subtract reference
      spectra. CONCLUSIONS: Linear unmixing, when judiciously performed, can accurately
      measure the abundance of CFP and YFP in mixed samples, even when their relative
      intensities range from 90:1.

PMID- 16888771
TI  - Flow cytometry controls, instrument setup, and the determination of positivity.
AB  - A frequent goal of flow cytometric analysis is to classify cells as positive or
      negative for a given marker, or to determine the precise ratio of positive to
      negative cells. This requires good and reproducible instrument setup, and careful
      use of controls for analyzing and interpreting the data. The type of controls to
      include in various kinds of flow cytometry experiments is a matter of some debate
      and discussion. In this tutorial, we classify controls in various categories,
      describe the options within each category, and discuss the merits of each option.

PMID- 16888772
TI  - Vibrational spectroscopic characteristics of secondary structure polypeptides in
      liquid water: constrained MD simulation studies.
AB  - Using the constrained MD simulation method in combination with quantum chemistry
      calculation, Hessian matrix reconstruction, and fragmentation approximation
      methods, we established a computational scheme for numerical simulations of amide
      I IR absorption, vibrational circular dichroism (VCD), and 2D IR photon echo
      spectra of peptides in solution. Six different secondary structure peptides,
      i.e., alpha-helix, 3(10)-helix, pi-helix, antiparallel and parallel beta-sheets,
      and polyproline II (P(II)), are considered, and the vibrational characteristic
      features in their linear and nonlinear spectra in the amide I band region are
      discussed. Isotope-labeling effects on IR and VCD spectra are notable only for
      alpha- and pi-helical peptides due to the strong vibrational couplings between
      two nearest neighboring amide I local oscillators. The amplitudes of difference
      2D IR spectra are shown to be strongly dependent on both the extent of mode
      delocalization and the relative orientation of local mode transition dipoles
      determined by secondary structure.

PMID- 16888774
TI  - Emerging techniques: whole-body screening and staging with MRI.
AB  - Strategies for screening or tumor staging include various modalities such as
      plain radiography, computed tomography (CT), MRI, and ultrasound. Technical
      innovations have created the feasibility to use MRI to image the entire body in a
      relatively short time-period. Whole-body MRI may play a potentially important
      role in evaluating for cancer or vascular disease. This article describes the
      rationale for using MRI to display the entire body, the techniques employed in
      whole-body MRI, possibilities and limitations, and summarizes first clinical
      results for screening and staging purposes.

PMID- 16888773
TI  - The chemical synthesis of the GstI protein by NCL on a X-Met site.
AB  - The small GstI protein (63 amino acids) of Rhizobium leguminosarum is the
      endogenous inhibitor of the glnII (glutamine synthetase II) gene expression. It
      has been suggested that GstI has a predominantly beta-structure and mediates the
      block of translation and stabilization of glnII mRNA through direct binding to
      its 5' untranslated region. Because of the unavailability of adequate amounts of
      purified recombinant protein, the mechanism as well as the protein tridimensional
      structure remain very poorly understood. To obtain the full-length protein, we
      have undertaken the chemical synthesis of the protein by different approaches. In
      a first attempt, the stepwise synthesis was unsuccessful, with strong aggregation
      experienced on the N-terminal side, after residue 44 from the C-terminus. In a
      second approach, we set up the conditions to carry out a native chemical ligation
      (NCL). Albeit the protein contains two Cysteine residues, located at positions 40
      and 47, to minimize the size of the N-terminal segment to be synthesized, we have
      devised an alternative strategy of ligation on Met32, utilizing homoCys as the
      ligating moiety and then alkylating the resulting polypeptide with methyl iodide.
      New conditions to quantitatively methylate thiol groups in complex polypeptides
      have been conceived, obtaining the protein in very good yields and purity. A CD
      spectroscopy investigation has revealed that the protein does not adopt canonical
      secondary structures but is very rich in beta-structure (approximately 60%), in
      agreement with a previous study carried out on samples obtained by recombinant
      methods.

PMID- 16888775
TI  - Quantitative measurements of regional lung ventilation using helium-3 MRI in a
      methacholine-induced bronchoconstriction model.
AB  - PURPOSE: To demonstrate ventilation changes in an animal model of methacholine
      induced bronchoconstriction using hyperpolarized (HP) helium-3 (He-3) MRI.
      MATERIALS AND METHODS: Bronchoconstriction was induced in 11 healthy rats using
      an intravenous injection of methacholine. The He-3 was laser-polarized using a
      custom-built system. MRI studies were performed on a 2-Tesla bore magnet. Coronal
      dynamic ventilation images were obtained using a single inhalation of the laser
      polarized He-3 gas before and after methacholine injection. Ventilation image
      series were processed on a pixel-by-pixel basis to generate three regional
      ventilation parameters: gas flow rate, filling time, and maximum gas volume.
      Student's paired t-test was used for analysis. RESULTS: Ventilation image series
      with a temporal resolution of 5 msec were obtained before and after methacholine
      challenge. Quantitative regional gas dynamic information demonstrated
      statistically significant differences between the baseline and constricted
      states. Following methacholine injection, the mean flow values were significantly
      lower for the right lung (RL) (P = 0.006) and left lung (LL) (P = 0.024), while
      the mean filling time was found to be greater (RL: P = 0.08, LL: P = 0.021). Gas
      volume values at maximum inspiration were found to be significantly lower after
      methacholine (RL: P = 0.002; LL: P = 0.036). CONCLUSION: He-3 MRI demonstrated
      and quantified regional ventilation changes in bronchoconstriction conditions in
      rats.

PMID- 16888777
TI  - Adult celiac disease: what is the role of MRI?
AB  - PURPOSE: To evaluate the ability of MRI to identify intra- and extraintestinal
      findings of celiac disease in an adult population. MATERIALS AND METHODS: Forty
      one subjects (18 men and 23 women; mean age = 41.3 years; 31 with biopsy-proven
      celiac disease, and 10 healthy volunteers) underwent MRI of the small bowel. MR
      studies were performed on a 1.5-T magnet using T2-weighted half-Fourier single
      shot turbo spin-echo (HASTE) and true fast imaging in steady-state precession
      (True-FISP) sequences. The MR features and sensitivity, and the specificity and
      accuracy of some of these features are described. RESULTS: In the 31 celiac
      patients, MRI showed bowel dilatation in 61.3% (N = 19), increased number of
      ileal folds in 48.4% (N = 15), reversed fold pattern abnormality in 38.7% (N =
      12), increased wall thickness in 16.1% (N = 5), duodenal stenosis in 6.5% (N =
      2), intussusception in 12.9% (N = 4), mesenteric lymphadenopathy in 41.9% (N =
      13), mesenteric vascular changes in 22.6% (N = 7), ascites in 6.5% (N = 2), and
      no abnormalities in 12.9% (N = 4). The volunteers had unremarkable exams. The
      overall specificity and accuracy were 100%, and sensitivity was 79% and 75% for
      increased number of ileal folders and reversed fold pattern abnormality,
      respectively. CONCLUSION: MRI is able to demonstrate intra- and extraintestinal
      features that may lead to the diagnosis of celiac disease in adults.

PMID- 16888776
TI  - Feasibility of dynamic susceptibility contrast perfusion MR imaging at 3T using a
      standard quadrature head coil and eight-channel phased-array coil with and
      without SENSE reconstruction.
AB  - PURPOSE: To investigate changes in image and dynamic signal-to-noise ratios
      (SNRs) of the DeltaR2* curve, as well as magnetic susceptibility-induced
      artifacts between a standard quadrature head coil and an eight-channel phased
      array coil with and without sensitivity-encoding (SENSE) at 3T, compared to the
      current clinical standard head coil acquisition at 1.5T. MATERIALS AND METHODS:
      Dynamic susceptibility contrast (DSC) perfusion MRI was performed on 80 brain
      tumor patients using a gradient-echo, echo-planar imaging (EPI) sequence. Image
      and dynamic SNR were compared between 1.5T and 3T field strengths, a quadrature
      and eight-channel phased-array coil, and a conventional vs. partially parallel
      EPI acquisition with SENSE reconstruction. The amount of geometric distortion and
      signal dropout was quantified and compared between conventional and SENSE EPI
      acquisitions within the same exam at 3T. RESULTS: An initial 2.6-fold elevation
      in dynamic SNR was observed in normal-appearing white matter when doubling the
      field strength (P < 0.001), with an additional 1.7-fold increase found when
      employing an eight-channel phased-array coil (P < 0.002). Compared to the
      standard 3T eight-channel coil acquisition, the implementation of SENSE reduced
      the number of voxels experiencing large anterior shifts in the phase-encode
      direction, lowered the volume of signal dropout by 2.0-11.5%, and allowed a 1.4
      fold increase in slice coverage, while only decreasing the dynamic SNR by 22%.
      CONCLUSION: SENSE EPI at 3T yielded a significant improvement in dynamic SNR over
      the 1.5T acquisitions. A significant reduction in magnetic susceptibility-induced
      artifacts was achieved with SENSE EPI compared to the standard EPI eight-channel
      coil acquisition at 3T.

PMID- 16888778
TI  - Focal adhesion signaling is required for myometrial ERK activation and
      contractile phenotype switch before labor.
AB  - In late pregnancy rapidly increasing fetal growth dramatically increases uterine
      wall tension. This process has been implicated in the activation of the
      myometrium for labor, but the mechanisms involved are unclear. Here, we tested,
      using a rat model, the hypothesis that gestation-dependent stretch, via
      activation of focal adhesion signaling, contributes to the published activation
      of myometrial ERK at the end of pregnancy. Consistent with this hypothesis, we
      show here that ERK is targeted to adhesion plaques during late pregnancy.
      Furthermore, myometrial stretch triggers a dramatic increase in myometrial
      contractility and ERK and caldesmon phosphorylation, confirming the presence of
      stretch sensitive myometrial signaling element. Screening by anti-phosphotyrosine
      immunoblotting for focal adhesion signaling in response to stretch reveals a
      significant increase in the tyrosine phosphorylated bands identified as focal
      adhesion kinase (FAK), A-Raf, paxillin, and Src. Pretreatment with PP2, a Src
      inhibitor, significantly suppresses the stretch-induced increases in FAK,
      paxillin, Src, ERK and caldesmon phosphorylation and myometrial contractility.
      Thus, focal adhesion-Src signaling contributes to ERK activation and promotes
      contraction in late pregnancy. These results point to focal adhesion signaling
      molecules as potential targets in the modulation of the myometrial contractility
      and the onset of labor.

PMID- 16888779
TI  - Molecular and immunohistochemical analyses of cardiac troponin T during cardiac
      development in the Mexican axolotl, Ambystoma mexicanum.
AB  - The Mexican axolotl, Ambystoma mexicanum, is an excellent animal model for
      studying heart development because it carries a naturally occurring recessive
      genetic mutation, designated gene c, for cardiac nonfunction. The double
      recessive mutants (c/c) fail to form organized myofibrils in the cardiac
      myoblasts resulting in hearts that fail to beat. Tropomyosin expression patterns
      have been studied in detail and show dramatically decreased expression in the
      hearts of homozygous mutant embryos. Because of the direct interaction between
      tropomyosin and troponin T (TnT), and the crucial functions of TnT in the
      regulation of striated muscle contraction, we have expanded our studies on this
      animal model to characterize the expression of the TnT gene in cardiac muscle
      throughout normal axolotl development as well as in mutant axolotls. In addition,
      we have succeeded in cloning the full-length cardiac troponin T (cTnT) cDNA from
      axolotl hearts. Confocal microscopy has shown a substantial, but reduced,
      expression of TnT protein in the mutant hearts when compared to normal during
      embryonic development.

PMID- 16888781
TI  - Cardiac tamponade as the presenting symptom of chronic myelogenous leukemia.

PMID- 16888780
TI  - FAP-1-mediated activation of NF-kappaB induces resistance of head and neck cancer
      to Fas-induced apoptosis.
AB  - Molecular mechanisms responsible for tumor resistance to apoptosis often involve
      the Fas/FasL pathway. While squamous cell carcinomas of the head and neck (SCCHN)
      express both Fas and FasL, their resistance to self-induced apoptosis or
      apoptosis mediated by Fas agonistic antibody (CH-11Ab) was independent of the
      level of Fas surface expression or the presence of soluble Fas in supernatants of
      primary or metastatic SCCHN cell lines. By in vitro immunoselection, using PCI
      15A cell line treated with successive cycles of CH-11 Ab, Fas-resistant sublines
      with the parental genotype were selected. Such sublines failed to cleave caspase
      8 upon Fas engagement and were resistant to CH-11 Ab, although they remained
      sensitive to VP-16 or staurosporin. In the presence of cycloheximide, the
      selected SCCHN sublines become susceptible to CH-11 Ab, and showed cleavage of
      caspase-8, suggesting that apoptosis resistance was mediated by an inhibitory
      protein(s) acting upstream of caspase-8. Overexpression of Fas-associated
      phosphatase 1 (FAP-1), but not cellular FLICE-inhibitory protein (cFLIP) in SCCHN
      sublines was documented by Western blots and RT-PCR analyses. The FAP-1+ selected
      sublines also downregulated cell surface Fas. A high phosphorylation level of
      IkappaB kappa, NFkappaB activation and upregulation of Bcl-2 expression were
      observed in the FAP-1+ sublines. Treatment with the phosphatase inhibitor,
      orthovanadate, or silencing of FAP-1 with siRNA abolished their resistance to
      apoptosis, suggesting that FAP-1 phosphatase activity could be responsible for NF
      kappaB activation and resistance of SCCHN cells to Fas-mediated apoptosis.

PMID- 16888782
TI  - Waldenstrom's macroglobulinemia presenting with spinal cord compression: a case
      report.
AB  - Waldenstrom's macroglobulinemia (WM) is a rare lymphoplasmacytic lymphoma
      characterized by a wide range of clinical presentations related to direct tumor
      infiltration and the production of IgM. Most commonly it presents with cytopenia,
      hepatosplenomegaly, lymphadenopathy, constitutional symptoms, and hyperviscosity
      syndrome. We report a case of WM in an 81-year-old man who initially presented
      with severe back pain. The patient had no peripheral lymphadenopathy or
      hepatosplenomegaly and his peripheral blood smear was normal. MRI of the spine
      revealed an epidural mass causing spinal cord compression at T9. Surgical
      decompression was performed and pathological analysis of the mass revealed a
      lymphoproliferative B-cell process. The diagnosis of WM was established after
      cytomorphologic and immunohistochemical analysis of the patient's bone marrow
      revealed the presence of a lymphoid/lymphoplasmacytoid-like bone marrow
      infiltrate along with an elevated serum IgM level. The patient responded both
      clinically and serologically to local radiotherapy. This case is unusual because
      the patient lacked all common clinical features of WM. This is the first reported
      case of epidural spinal cord compression as the initial manifestation of WM,
      adding to the spectrum of clinical presentations seen in this disease.

PMID- 16888783
TI  - VAD combination chemotherapy followed by bortezomib may be an effective treatment
      in secondary plasma cell leukemia.

PMID- 16888784
TI  - Effect of blood cyclosporine concentration on the outcome of hematopoietic stem
      cell transplantation from an HLA-matched sibling donor.
AB  - We retrospectively evaluated the effect of the blood cyclosporine (CsA)
      concentration on the outcome of allogeneic hematopoietic stem cell
      transplantation from an HLA-matched sibling donor in 171 patients who received a
      continuous infusion of CsA and short-course methotrexate to prevent graft-versus
      host disease (GVHD). CsA was started at 3.0 mg/kg/day and the dose was adjusted
      to maintain the blood CsA concentration between 250 and 350 ng/ml. The actual
      dose of CsA averaged 1.9 mg/kg/day at the 3rd week after transplantation. The
      incidence of grade II-IV acute GVHD was 29.9%. Patient age and sex were
      identified as independent significant risk factors for acute GVHD. The CsA
      concentration during the 3rd week after transplantation most strongly affected
      the incidence of grade II-IV acute GVHD (RR 0.995 for an increase in CsA
      concentration by 1 ng/ml, P = 0.037) adjusted for other risk factors. The
      incidence of acute GVHD was significantly lower in patients with a 3rd-week CsA
      concentration higher than 300 ng/ml than in those with values between 200 and 300
      ng/ml (20% vs. 35%, P = 0.036). We concluded that the blood CsA concentration at
      peri-engraftment period may be important in preventing acute GVHD.

PMID- 16888786
TI  - High-dose therapy and autologous peripheral blood stem cells transplantation
      followed by a very low reduced intensity regimen with fludarabine +
      cyclophosphamide and allograft improve complete remission rate in de novo
      multiple myeloma patients.
AB  - The recent development of reduced intensity conditioning and allotransplantation
      (RICT) has opened a new way to assure engraftment of donor cells while reducing
      early transplant-related mortality. We evaluated the combination of high-dose
      therapy and autologous peripheral blood stem cells transplantation (APBSCT)
      followed by RICT to extend the benefit of allografting procedures in de novo
      multiple myeloma (MM) patients. Fifteen subjects with stage III MM (median age 51
      years, range 40-57) received high dose melphalan (200 mg/m(2)) followed by APBSCT
      previously collected after cyclophosphamide (4 g/m(2)) and granulocyte colony
      stimulating factor (G-CSF). After 3-4 months from APBSCT, the patients underwent
      RICT, consisting of fludarabine 30 mg/m(2) + cyclophosphamide 300 mg/m(2) on days
      -4, -3, and -2. Acute graft-versus-host disease (GVHD) occurred in 2 patients; 6
      patients developed chronic GVHD; 4 patients developed CMV antigenemia and were
      treated pre-emptively with ganciclovir. No transplant related mortality was
      shown. Response was simultaneously measured by both electrophoresis (EP) and
      immunofixation (IF); when IF was negative, patients were classified in complete
      remission (CR) and when it remained positive, near CR (nCR). After a median
      follow up of 44 months post APBSCT, 100 and 43% of patients are still alive and
      progression-free, respectively. Overall, the CR + nCR rate after dose-reduced
      allograft was enhanced from 26.7 to 73.3%. A correlation not statistically
      significant between GVHD and remission was found. In conclusion, an up-front
      tandem strategy with a very low reduced intensity-conditioning regimen for
      allografting following autografting is feasible and induces high CR/nCR rate in
      MM.

PMID- 16888785
TI  - Molecular profiling of chronic myeloid leukemia in eastern India.
AB  - Molecular breakpoint of the BCR-ABL fusion gene has been characterized for 122
      chronic myeloid leukemia patients. Out of 122 cases, 33 b2a2, 69 b3a2, 2 e1a2,
      and 2 e19a2 cases have been detected. Six coexpressed both b2a2 and b3a2
      transcripts. All the coexpressing samples had an A>G polymorphism at the putative
      splice branchpoint in intron 13. The T>C polymorphism in exon 13, reported to be
      linked to coexpression, was not present in all the coexpressing patients. No
      correlation of transcript type with platelet count was detected. Those expressing
      b2a2 transcript were diagnosed at relatively younger age and with higher white
      blood cell count, in agreement with other reports. However, the correlation was
      not statistically significant.

PMID- 16888787
TI  - Outcomes in the treatment of thrombotic thrombocytopenic purpura with
      splenectomy: a retrospective cohort study.
AB  - The mainstay of treatment for thrombotic thrombocytopenic purpura (TTP) is plasma
      exchange (PE), but the role of splenectomy is still undefined. The records of all
      patients with TTP at a single center over a 20-year period were retrospectively
      reviewed. Response to plasma exchange was determined. The outcome of patients
      treated with splenectomy in the setting of TTP was evaluated. Sixty-one patients
      had been treated for TTP. Thirty-nine patients (64%) achieved complete remission
      (CR) with PE, nineteen (31%) of these achieving sustained CR and seventeen (28%)
      with relapsed TTP. Twenty patients (33%) had PE refractory TTP and two patients
      (3%) had PE dependent TTP. During this time period, 10 patients (16%) underwent
      splenectomy, four patients (7%) for PE dependent TTP, three (5%) for relapsed
      TTP, and three (5%) for refractory TTP. All of the patients achieved CR after
      splenectomy. Two patients who had undergone splenectomy had subsequent relapses,
      both with previously relapsed TTP. In relapsed patients the relapse rate after
      splenectomy was 0.27 events per patient year compared to 0.6 events per patient
      year before splenectomy. Median follow-up after splenectomy was 19 months (range
      0.13-90 months). In conclusion, relapses in TTP can be managed successfully with
      additional PE or with splenectomy. PE dependent or refractory TTP can be
      successfully treated with splenectomy.

PMID- 16888788
TI  - A case of myelodysplastic syndrome with erythroid hypoplasia associated with a
      familial translocation t(3;14)(p21.1;q24.1).
AB  - Myelodysplastic syndrome (MDS) with erythroid hypoplasia, a rare form of MDS, has
      not yet been clearly defined. We report here a 20-year-old woman with severe
      transfusion-dependent anemia and reticulocytopenia. White blood cells and
      platelet counts were normal. Bone marrow examination showed a low percentage of
      erythroid precursors (6%) and a marked dyserythropoiesis and dysmegakaryopoiesis.
      A diagnosis of MDS (refractory anemia according to the FAB classification) with
      erythroid hypoplasia was made. Cytogenetic analysis of the bone marrow and
      peripheral blood revealed a 46,XX,t(3;14)(p21.1;q24.1) translocation, which was
      confirmed by fluorescence in situ hybridization analysis. This translocation was
      detected in the apparently healthy younger brother, father, and aunt (father's
      sister) of the patient. Clonality of T cells in the patient was not confirmed by
      the polymerase chain reaction and heteroduplex temperature-gradient gel
      electrophoresis. IgM serology for B19 parvovirus was negative. Other conditions
      known to be associated with erythroid hypoplasia, such as thymoma, were not
      present. The patient failed to respond to immunosuppressive therapy
      (antithymocyte globulin and cyclosporin A). Administration of recombinant human
      erythropoietin improved her anemia. To our knowledge, this balanced
      translocation, namely t(3;14)(p21.1;q24.1), which is present both in the patient
      with MDS with erythroid hypoplasia and in the healthy members of the family, has
      not been defined previously.

PMID- 16888789
TI  - A rare occurrence of diffuse lymphoblastic lymphoma in pregnancy.

PMID- 16888790
TI  - Evaluation of hepatic lesions and hepatic parenchyma using diffusion-weighted
      echo-planar MR with three values of gradient b-factor.
AB  - PURPOSE: To determine whether diffusion-weighted echo-planar (EP) MR images with
      very small, small, and large gradient b-factors are useful in evaluating hepatic
      lesions and hepatic parenchyma. MATERIALS AND METHODS: Approximate values of the
      apparent diffusion coefficients for diffusion (D) and for flowing spins (D*) for
      96 hepatic lesions (26 hepatocellular carcinomas [HCCs], 28 metastases, 26
      hemangiomas, and 16 cysts) and the non-lesion-bearing regions of parenchyma in 78
      livers (50 noncirrhotic and 28 cirrhotic) were calculated from EP images
      (modified for gradient b-factors of 3, 50, and 300 second/mm(2)). RESULTS: Liver
      cysts and noncirrhotic livers showed statistically higher mean D* values than
      HCCs, hemangiomas, metastases, and cirrhotic livers (P < 0.05 on Scheffe post hoc
      analysis). Liver cysts showed statistically higher mean D values than HCCs,
      metastases, noncirrhotic livers, and cirrhotic livers (P < 0.05). Liver
      hemangiomas showed statistically higher mean D values than HCCs, noncirrhotic
      livers, and cirrhotic livers (P < 0.05). CONCLUSION: The D* value in addition to
      the D value may be useful for evaluating the nature of diffusion and flowing
      spins in hepatic lesions and hepatic parenchyma.

PMID- 16888791
TI  - Histone deacetylase inhibitor FK228 is a potent inducer of human fetal
      hemoglobin.
AB  - We investigated the induction of the human fetal globin gene using five potent
      histone deacetylase (HDAC) inhibitors: FK-228, HC-Toxin, Trichostatin, MS-275,
      and Apicidin, using in vitro assays and cultures of primary human erythroblasts.
      The results showed that FK228 is the most potent inducer of fetal hemoglobin and
      exhibits its effects in picomolar concentrations. FK228 should be considered as a
      potential therapeutic for induction of fetal hemoglobin in patients with beta
      chain hemoglobinopathies.

PMID- 16888792
TI  - Apparent diffusion coefficient in malignant lymphoma and carcinoma involving
      cavernous sinus evaluated by line scan diffusion-weighted imaging.
AB  - PURPOSE: To evaluate the apparent diffusion coefficient (ADC) of malignant
      lymphomas and carcinomas involving cavernous sinus by line scan diffusion
      weighted imaging (LSDWI) and to determine the usefulness of this method for
      differentiating between the two tumors. MATERIALS AND METHODS: Four patients with
      malignant lymphomas and six patients with carcinomas were prospectively studied.
      LSDWI images were obtained with two different b values of 5 seconds/mm(2) and
      1000 seconds/mm(2) in the coronal plane. The ADC values of the two types of
      tumors were calculated and compared. RESULTS: LSDWI provided diagnostic images
      with minimum susceptibility artifacts and enabled measurement of the ADC. The ADC
      value (mean +/- SD) was 0.51 +/- 0.06 x 10(-3) mm(2)/second in malignant
      lymphomas and 0.99 +/- 0.08 x 10(-3) mm(2)/second in carcinomas. A significant
      difference in ADC values was found between the two (P < 0.01). CONCLUSION:
      Malignant lymphomas showed significantly lower ADC value than carcinomas. ADC
      provides additional useful information about differentiation between these
      tumors.

PMID- 16888793
TI  - The interplay of sequence and stereochemistry in defining conformation in
      proteins and polypeptides.
AB  - Sequential specification of conformation in proteins and polypeptides is a
      triangular interplay involving the system of linked peptides, the sequences in
      side chains, and water as solvent. Stereochemistry in side chain linkages is
      obviously important in the interaction between all of the players, but no
      specification of its explicit role, if any, in linking sequence with conformation
      has been made. Flory and coworkers made a puzzling observation in 1967 that, when
      mutated from poly-L to alternating-L,D stereochemical structure, polypeptides
      will suffer a reduction in overall dimension or characteristic ratio by an
      astonishing factor of 10 and to a value even lower than that predicted for free
      rotation (Miller, W. G.; Brant, D. A.; Flory, P. J. J Mol Biol 1967, 23, 67-80).
      Enquiring into this longstanding puzzle, Durani and coworkers found that the
      stereochemical modification will also abolish conformational sensitivity in
      polypeptide structure to solvent, because electrostatic interactions in the
      system of linked peptides are transformed from a condition of mutual conflict to
      one of harmony (Ramakrishnan, V.; Ranbhor, R.; Kumar, A.; Durani, S. J Phys Chem
      B 2006, 110, 9314-9323). Thus, poly-L stereochemistry could be the fulcrum
      linking sequences with phi,psis in protein and polypeptide structures, via
      dielectric arbitrations in a conflicting type of interpeptide electrostatics, in
      agreement with the electrostatic screening model of Avbelj and Moult (Avbelj, F.;
      Moult, J. Biochemistry 1995, 34, 755-764).

PMID- 16888794
TI  - Hyperintense nodules on non-enhanced T1-weighted gradient-echo magnetic resonance
      imaging of cirrhotic liver: fate and clinical implications.
AB  - PURPOSE: To investigate the fate of hyperintense hepatic nodules on nonenhanced
      T1-weighted (T1w) gradient-echo (GRE) magnetic resonance (MR) images in cirrhotic
      patients. MATERIALS AND METHODS: A total of 79 cirrhotic patients with
      hyperintense nodules (>5 mm) on precontrast opposed-phase (repetition time
      (TR)/echo time (TE) = 140/2.7 msec) GRE images from initial MRI without T2
      weighted (T2w) hyperintensity or arterial hypervascularity were subjected to
      analysis of subsequent MR images obtained at intervals of 12-56 months (mean =
      24.5 months). Multiplicity of hyperintense nodules (group A, up to 8; group B,
      >8) was correlated with follow-up changes. RESULTS: Group B patients were younger
      (P = 0.003) than group A patients (mean = 47.5 and 56.2 years, respectively). In
      66 group A patients, 39 out of 143 lesions (27%) were enlarged, including 20
      malignantly transformed or borderline lesions. Of the 104 lesions (the eight
      largest lesions in each patient) in 13 group B patients, only three (2.9%) were
      enlarged. The results of best- and worst-case analyses showed that overall the
      lesions were benign in 91% and 82% of patients, respectively. CONCLUSION: T1w
      hyperintense nodules without T2w hyperintensity or arterial hypervascularity in
      the cirrhotic liver are benign in most cases. In younger patients with numerous
      macronodules, almost all of these lesions follow a benign course.

PMID- 16888795
TI  - Elevated mRNA levels of DNA methyltransferase-1 as an independent prognostic
      factor in primary nonsmall cell lung cancer.
AB  - BACKGROUND: Despite many reports about the involvement of DNA methyltransferases
      (DNMTs) in human cancers, including nonsmall cell lung cancer (NSCLC), the
      clinicopathologic significance of DNMTs in primary NSCLC remains to be
      elucidated. METHODS: The relation between the mRNA levels of DNMTs (1 and 3b) and
      the promoter methylation of the p16, RARbeta2, H-cadherin, GSTP1, RIZ, and FHIT
      genes and the clinicopathologic features in 102 fresh-frozen tissues and paraffin
      blocks were retrospectively studied. The mRNA levels of the DNMTs were assessed
      via semiquantitative reverse-transcription polymerase chain reaction (RT-PCR),
      and the methylation status of the CpG islands were determined by methylation
      specific PCR. RESULTS: The mRNA levels of DNMT1 and DNMT3b were elevated in 53%
      and 58% of 102 NSCLCs, respectively. Hypermethylation of p16, RARbeta2, H
      cadherin, GSTP1, RIZ, and FHIT occurred in 37%, 38%, 34%, 18%, 9%, and 31% of
      patients, respectively. Univariate analysis showed that elevated DNMT mRNA levels
      were not significantly associated with the hypermethylation of 6 genes. However,
      the elevated mRNA levels of DNMT1 were determined to be significantly associated
      with the hypermethylation of the p16 promoter (odds ratio [OR] = 2.70, 95%
      confidence interval [95% CI], 1.02-7.15; P = .02), after controlling for age,
      gender, pack-years smoked, histology, and pathologic stage. The hazard of failure
      in cases with elevated mRNA levels of DNMT1 was 3.51 (95% CI, 1.18-12.76; P =
      .02) times higher than that in those without. The elevated mRNA levels of DNMT3b
      were not ultimately associated with patient prognosis. CONCLUSIONS: Elevated mRNA
      expression of DNMT1 may be an independent prognostic factor in NSCLC and CpG
      island hypermethylation in NSCLC may be maintained by a complex interaction of
      several factors rather than by a simple transcriptional up-regulation of DNMT1.

PMID- 16888796
TI  - Focal Wallerian degeneration of the corpus callosum in large middle cerebral
      artery stroke: serial diffusion tensor imaging.
AB  - PURPOSE: To detect lesion-related focal Wallerian degeneration (WD) changes in
      different segments of the corpus callosum (CC) in patients with large middle
      cerebral arterial (MCA) territory stroke using diffusion tensor imaging (DTI).
      MATERIALS AND METHODS: Eight patients underwent DTI scans at three different time
      points: six to eight weeks, 10-12 weeks, and beyond six months of stroke onset.
      Eight healthy age-matched controls were also scanned using the same protocol at
      three different time points. Region-of-interest (ROI) analysis was performed on
      seven segments of the CC to determine the fractional anisotropy (FA), mean
      diffusivity (MD), and corresponding callosal cross-sectional areas. RESULTS: On
      repeated-measures analysis of variance (ANOVA), a significant reduction in the FA
      values was observed from the first to the third study compared to controls,
      reflecting temporal degeneration in the rostrum, genu, rostral body, anterior
      midbody, and splenium of the CC. However, a significant temporal elevation in MD
      values was observed in only the rostral body and anterior midbody of the CC. This
      was associated with a significant region-specific reduction in the cross
      sectional areas at time points beyond six months, and appears to be consistent
      with the loss of callosal structural components due to interruption of the
      cortico-callosal fibers secondary to WD. CONCLUSION: These results indicate that
      cortico-callosal topographical changes exhibit a significant temporal decline in
      observed FA values that is suggestive of cortico-callosal WD in patients with
      large MCA territory stroke.

PMID- 16888797
TI  - MRI detects myocardial iron in the human heart.
AB  - Iron-induced cardiac dysfunction is a leading cause of death in transfusion
      dependent anemia. MRI relaxation rates R2(1/T2) and R2*(1/T2*) accurately predict
      liver iron concentration, but their ability to predict cardiac iron has been
      challenged by some investigators. Studies in animal models support similar R2 and
      R2* behavior with heart and liver iron, but human studies are lacking. To
      determine the relationship between MRI relaxivities and cardiac iron, regional
      variations in R2 and R2* were compared with iron distribution in one freshly
      deceased, unfixed, iron-loaded heart. R2 and R2* were proportionally related to
      regional iron concentrations and highly concordant with one another within the
      interventricular septum. A comparison of postmortem and in vitro measurements
      supports the notion that cardiac R2* should be assessed in the septum rather than
      the whole heart. These data, along with measurements from controls, provide
      bounds on MRI-iron calibration curves in human heart and further support the
      clinical use of cardiac MRI in iron-overload syndromes.

PMID- 16888799
TI  - Nuclear localization of liver X receptor alpha and beta is differentially
      regulated.
AB  - Activity of nuclear receptors is regulated by their nuclear localization. Liver X
      receptors (LXR) alpha and beta are nuclear receptors that regulate transcription
      of genes for cholesterol metabolism, cholesterol transport, and lipogenesis.
      While LXR alpha and beta are very similar in structure and exhibit similar ligand
      binding properties, their physiological roles are quite different. Since the LXRs
      fall into a class of receptors that move between the nucleus and cytoplasm,
      experiments were conducted to determine whether LXR alpha and LXR beta show
      differences in their nuclear localization pattern. To determine the location of
      each receptor, cell lines stably expressing yellow fluorescent protein (YFP)
      chimeras with either LXR alpha or LXR beta were examined. Retention in the
      nucleus of the chimeric proteins in the presence or absence of ligands was
      assessed using fluorescence microscopy coupled with digitonin permeabilization
      assays. Surprisingly, differences were found between LXR alpha and LXR beta.
      Whereas unliganded LXR alpha was retained in the nucleus, unliganded LXR beta was
      partially exported. Mutations were then introduced into putative nuclear
      localization sequences (NLS) to determine which sequences are important for
      nuclear localization and function. Mutation in one such sequence abolished
      nuclear localization of LXR alpha, whereas the analogous change in LXR beta had a
      much less dramatic effect. Mutations in analogous putative NLS also
      differentially affected transcriptional activation by LXR alpha and LXR beta.
      These data demonstrate for the first time that nuclear retention and localization
      as well as function of LXR alpha and LXR beta are differentially regulated.

PMID- 16888800
TI  - Limited plasticity of mesenchymal stem cells cocultured with adult
      cardiomyocytes.
AB  - In order to assess, in a controlled in vitro model, the differentiation potential
      of adult bone marrow derived stem cells we have developed a coculture procedure
      using adult rat cardiomyocytes and mesenchymal stem cells (MSCs) from transgenic
      GFP positive rats. We investigated in the cocultured MSCs the time course of
      cellular processes that are difficult to monitor in in vivo experiments. Adult
      rat cardiomyocytes and adult rat MSCs were cocultured for up to 7 days and
      analyzed by confocal microscopy. Several markers were studied by
      immunofluorescence technique. The fluorescent ST-BODIPY-Dihydropyridine was used
      to label calcium channels in living cells. Intracellular calcium was monitored
      with the fluorescent probe X-Rhod-1. Immunofluorescence experiments showed the
      presence of connexin-43 between cardiomyocytes and MSCs and between MSCs, while
      no sarcomeric structures were observed at any time of the coculture. We looked at
      the expression of calcium channels and development of voltage-dependent calcium
      signaling in cocultured MSCs. MSCs showed a time-dependent increase of labeling
      of ST-BODIPY-Dihydropyridine, reaching a relatively strong level after 72 h of
      coculture. The treatment with a non-fluorescent DHP, Nifedipine, completely
      abolished ST-BODIPY labeling. We investigated whether depolarization could
      modulate intracellular calcium. Depolarization-induced calcium transients
      increased in MSCs in relation to the coculture time. We conclude that MSCs
      cocultured with adult cardiomyocytes present preliminary evidence of voltage
      dependent calcium modulation uncoupled with the development of nascent or adult
      myofibrils, thus showing a limited lineage specification and a low plasticity to
      differentiate in a full cardiomyocyte-like phenotype.

PMID- 16888801
TI  - Regulation of Sprouty2 stability by mammalian Seven-in-Absentia homolog 2.
AB  - Mammalian Sprouty (Spry) gene expression is rapidly induced upon activation of
      the FGF receptor signaling pathway in multiple cell types including cells of
      mesenchymal and epithelial origin. Spry2 inhibits FGF-dependent ERK activation
      and thus Spry acts as a feedback inhibitor of FGF-mediated proliferation. In
      addition, Spry2 interacts with the ring-finger-containing E3 ubiquitin ligase, c
      Cbl, in a manner that is dependent upon phosphorylation of Tyr55 of Spry2. This
      interaction results in the poly-ubiquitination and subsequent degradation of
      Spry2 by the proteasome. Here, we describe the identification of another E3
      ubiquitin ligase, human Seven-in-Absentia homolog-2 (SIAH2), as a Spry2
      interacting protein. We show by yeast two-hybrid analysis that the N-terminal
      domain of Spry2 and the ring finger domain of SIAH2 mediated this interaction. Co
      expression of SIAH2 resulted in proteasomal degradation of Spry1, 2, and to a
      lesser extent Spry4. The related E3 ubiquitin-ligase, SIAH1, had little effect on
      Spry2 protein stability when co-expressed. Unlike c-Cbl-mediated degradation of
      Spry2, SIAH2-mediated degradation was independent of phosphorylation of Spry2 on
      Tyr55. Spry2 was also phosphorylated on Tyr227, and phosphorylation of this
      residue was also dispensable for SIAH2-mediated degradation of Spry2. Finally, co
      expression of SIAH2 with Spry2 resulted in a rescue of FGF2-mediated ERK
      phosphorylation. These data suggest a novel mechanism whereby Spry2 stability is
      regulated in a manner that is independent of tyrosine phosphorylation, and
      provides an addition level of control of Spry2 protein levels.

PMID- 16888802
TI  - Prostaglandin F2alpha inhibits adipocyte differentiation via a G alpha q-calcium
      calcineurin-dependent signaling pathway.
AB  - Prostaglandin F2alpha (PGF2alpha) is a potent physiological inhibitor of
      adipocyte differentiation, however the specific signaling pathways and molecular
      mechanisms involved in mediating its anti-adipogenic effects are not well
      understood. In the current study, we now provide evidence that PGF2alpha inhibits
      adipocyte differentiation via a signaling pathway that requires heterotrimeric G
      protein G alpha q subunits, the elevation of the intracellular calcium
      concentration ([Ca2+]i), and the activation of the Ca2+/calmodulin-regulated
      serine/threonine phosphatase calcineurin. We show that while this pathway acts to
      inhibit an early step in the adipogenic cascade, it does not interfere with the
      initial mitotic clonal expansion phase of adipogenesis, nor does it affect either
      the expression, DNA binding activity or differentiation-induced phosphorylation
      of the early transcription factor C/EBPbeta. Instead, we find that PGF2alpha
      inhibits adipocyte differentiation via a calcineurin-dependent mechanism that
      acts to prevent the expression of the critical pro-adipogenic transcription
      factors PPARgamma and C/EBPalpha. Furthermore, we demonstrate that the inhibitory
      effects of PGF2alpha on both the expression of PPARgamma and C/EBPalpha and
      subsequent adipogenesis can be attenuated by treatment of preadipocytes with the
      histone deacetylase (HDAC) inhibitor trichostatin A. Taken together, these
      results indicate that PGF2alpha inhibits adipocyte differentiation via a G alpha
      q-Ca2+-calcineurin-dependent signaling pathway that acts to block expression of
      PPARgamma and C/EBPalpha by a mechanism that appears to involves an HDAC
      sensitive step.

PMID- 16888803
TI  - Twist negatively regulates osteoblastic differentiation in human periodontal
      ligament cells.
AB  - Periodontal ligament (PDL) is a thin fibrous connective tissue located between
      two mineralized tissues, alveolar bone and cementum, which maintains a constant
      width physiologically. The mechanisms by which PDL resists mineralization are not
      well understood. Twist is a basic helix loop helix protein that plays a central
      role in regulation of early osteogenesis. We investigated the localization of
      Twist in PDL and compared the expression of Twist and osteoblast-related genes in
      PDL cells with those in osteoblast-like cells in the presence or absence of
      recombinant human bone morphogenetic protein (BMP)-2. Histochemical analysis
      showed that Twist was expressed along alveolar bone surface in PDL. PDL cells
      constitutively expressed Twist gene and the expression level was higher than that
      in osteoblast-like cells. In osteoblast-like cell culture, BMP-2 enhanced
      osteoblast-related gene expression, while Twist expression was slightly
      decreased. In contrast, BMP-2 increased runt-related transcription factor (Runx)
      2, but failed to enhance alkaline phosphatase (ALP) and osteocalcin (OCN) gene
      expression in PDL cells. Interestingly, unlike in osteoblast-like cells, Twist
      expression was upregulated by BMP-2 in PDL cells. We transiently knocked down
      Twist gene in PDL cells using a short interference RNA expression vector
      (siTwist) and found that ALP, osteopontin (OPN), bone sialoprotein (BSP) genes
      expression and basal level of ALP activity were slightly increased, whereas Runx2
      and OCN genes were not affected. Collectively, these results suggest that Twist
      may act as a negative regulator of osteoblastic differentiation in PDL cells.

PMID- 16888804
TI  - Cytokines and hematopoietic stem cell mobilization.
AB  - Hematopoietic stem cell transplantation (HSCT) has become the standard of care
      for the treatment of many hematologic malignancies, chemotherapy sensitive
      relapsed acute leukemias or lymphomas, multiple myeloma; and for some non
      malignant diseases such as aplastic anemia and immunodeficient states. The
      hematopoietic stem cell (HSC) resides in the bone marrow (BM). A number of
      chemokines and cytokines have been shown in vivo and in clinical trials to
      enhance trafficking of HSC into the peripheral blood. This process, termed stem
      cell mobilization, results in the collection of HSC via apheresis for both
      autologous and allogeneic transplantation. Enhanced understanding of HSC biology,
      processes involved in HSC microenvironmental interactions and the critical
      ligands, receptors and cellular proteases involved in HSC homing and
      mobilization, with an emphasis on G-CSF induced HSC mobilization, form the basis
      of this review. We will describe the key features and dynamic processes involved
      in HSC mobilization and focus on the key ligand-receptor pairs including
      CXCR4/SDF1, VLA4/VCAM1, CD62L/PSGL, CD44/HA, and Kit/KL. In addition we will
      describe food and drug administration (FDA) approved and agents currently in
      clinical development for enhancing HSC mobilization and transplantation outcomes.

PMID- 16888805
TI  - Interleukin-1beta and tetradecanoylphorbol acetate-induced biosynthesis of tumor
      necrosis factor alpha in human hepatoma cells involves the transcription factors
      ATF2 and c-Jun and stress-activated protein kinases.
AB  - The proinflammatory cytokine tumor necrosis factor (TNF) alpha is mainly produced
      in cells from the monocyte/macrophage lineage. TNFalpha is also a key signaling
      molecule in the liver functioning as an important physiological and pathogenic
      mediator. In hepatocytes or human hepatoma cells TNFalpha is expressed at
      extremely low levels but TNFalpha biosynthesis can be induced by interleukin (IL)
      1beta or 12-O-tetradecanoylphorbol-13-acetate (TPA). Here, we show that IL-1beta
      and TPA stimulated TNFalpha gene transcription in hepatoma cells mediated by a
      composite TPA-responsive element/cAMP response element. Both IL-1beta and TPA
      triggered phosphorylation and activation of the basic region leucine zipper
      transcription factors c-Jun and ATF2 and expression of dominant-negative mutants
      of c-Jun and ATF2-reduced TNFalpha promoter activity and secretion of TNFalpha.
      Expression of the nuclear dual-specific MAP kinase phosphatase-1 (MKP-1) blocked
      TNFalpha promoter activity and TNFalpha secretion following IL-1beta or TPA
      stimulation, indicating that MKP-1 functions as a nuclear shut-of-device of IL
      1beta and TPA-induced TNFalpha expression.

PMID- 16888806
TI  - Nanotopographical stimulation of mechanotransduction and changes in interphase
      centromere positioning.
AB  - We apply a recently developed method for controlling the spreading of cultured
      cells using electron beam lithography (EBL) to create polymethylmethacrylate
      (PMMA) substrata with repeating nanostructures. There are indications that the
      reduced cell spreading on these substrata, compared with planar PMMA, results
      from a reduced adhesivity since there are fewer adhesive structures and fewer of
      their associated stress fibres. The reduced cell spreading also results in a
      reduced nuclear area and a closer spacing of centrosomes within the nucleus,
      suggesting that the tension applied to the nucleus is reduced as would be
      expected from the reduction in stress fibres. In order to obtain further evidence
      for this, we have used specific inhibitors of components of the cytoskeleton and
      have found effects comparable with those induced by the new substrata. We have
      also obtained evidence that these subtrata result in downregulation of gene
      expression which suggests that this may be due to the changed tension on the
      nucleus: an intriguing possibility that merits further investigation.

PMID- 16888807
TI  - Phosphatidic acid regulates the affinity of the murine phosphatidylinositol 4
      phosphate 5-kinase-Ibeta for phosphatidylinositol-4-phosphate.
AB  - Type I phosphatidylinositol 4-phosphate 5-kinase (PI4P5K) catalyzes the
      phosphorylation of phosphatidylinositol 4 phosphate [PI(4)P] at carbon 5,
      producing phosphatidylinositol 4,5 bisphosphate [PI(4,5)P2]. Phosphatidic acid
      (PA) activates PI4P5K in vitro and plays a central role in the activation of
      PIP5K pathways in vivo. This report demonstrates that actin fiber formation in
      murine fibroblasts involves PA activation of PIP5Ks and defines biochemical
      interactions between PA and the PIP5Ks. Inhibition of phospholipase D production
      of PA results in the loss of actin fibers. Overexpression of the beta isoform of
      the type I murine phosphatidylinositol 4-phosphate 5-kinase (mPIP5K-Ibeta)
      maintains actin fiber structure in the face of phospholipase D inhibition. PA
      activates mPIP5K-Ibeta by direct binding to mPIP5K-Ibeta through both
      electrostatic and hydrophobic interactions, with the fatty acid acyl chain length
      and degree of saturation acting as critical determinants of binding and
      activation. Furthermore, kinetic analysis suggests that phosphorylation of the
      PI(4)P substrate does not follow classical Michaelis-Menten kinetics. Instead,
      the kinetic data are consistent with a model in which mPIP5K-Ibeta initially
      binds to the lipid micelle and subsequently binds the PI(4)P substrate. In
      addition, the kinetics indicate substrate inhibition, suggesting that mPIP5K
      Ibeta contains an inhibitory PI(4)P-binding site. These results suggest a model
      in which mPIP5K-Ibeta is surrounded by PI(4)P, but is unable to catalyze its
      conversion to PI(4,5)P2 unless PA is bound.

PMID- 16888808
TI  - Elucidating progesterone effects in breast cancer: cross talk with PDGF signaling
      pathway in smooth muscle cell.
AB  - Several studies indicate that progesterone exerts relevant effects in breast
      tissue. However, the exact role of this steroid in breast cancer development and
      progression has not been elucidated. Here, we show that platelet-derived growth
      factor (PDGF)-A is one of the progesterone target genes on breast cancer MCF7 and
      T47D cells. A paracrine role for PDGF-A was investigated, since its receptor
      expression was down-regulated from breast cancer cells. Progesterone increased
      PDGF-A protein release as evaluated by Western blotting and ELISA. Medium from
      Progesterone-treated MCF7 cells resulted in phosphorylation of smooth muscle
      cells PDGF receptor alpha. This effect was not observed after treatment with PDGF
      inhibitor. MCF7 cells-secreted PDGF-A was able to increase smooth muscle cell
      viability and proliferation and decrease apoptosis, effects that were prevented
      by the use of a PDGF-A neutralizing antibody. Notably, cell invasion was not
      influenced by PDGF-A secreted by MCF7 cells. Our results elucidated for the first
      time the cross talk between progesterone and PDGF signaling pathway. The fact
      that MCF7-secreted PDGF elicited crucial roles in vascular wall smooth muscle
      cells, suggested a paracrine pathway for progesterone. Targeting these
      progesterone-induced processes may provide novel therapeutic strategies for
      hormone-dependent human breast cancer.

PMID- 16888809
TI  - Functional analysis of Survivin in spindle assembly in Xenopus egg extracts.
AB  - Survivin is a member of the inhibitor of apoptosis (IAP) protein family that
      serves critical roles in mitosis and cytokinesis. Many studies have suggested
      Survivin's involvement in spindle regulation, but direct biochemical evidence for
      this has been lacking. Using the cell-free system of Xenopus egg extracts, we
      tested whether Survivin was necessary for the assembly of metaphase spindles.
      Removal or inhibition of Xenopus Survivin causes the disruption in the formation
      of metaphase spindles. In particular, we observe the generation of microtubule
      (MT) asters or poorly formed shortened spindle structures. In the latter
      phenotype the spindle structures display a decrease pole-to-pole length and a
      reduction of MTs around the chromatin indicating that Survivin may promote the
      stabilization of MT-chromatin interactions. In addition, function analysis of
      Survivin's conserved phosphorylation site Thr34 (Thr43 in Xenopus) and tubulin
      binding domain was also assessed in regulating spindle assembly. Treatment of
      Xenopus egg extracts with a recombinant Survivin mutant that contained an alanine
      residue substitution at Thr43 (SURT43A mutant) or that was missing the C-terminal
      tubulin-binding domain (SURCL mutant) produced an increased frequency of MT
      asters and shorten abnormal spindle structures in Xenopus egg extracts.
      Interestingly, a phosphomimetic mutation made at residue Thr43 of Survivin
      (SURT43E mutant) generated a high frequency of MT asters implying that premature
      'activation' of Survivin may interfere with an early stage of spindle assembly.
      Taken together, we propose that Survivin is a necessary component of the mitotic
      spindle and its phosphorylation at residue Thr43 is important for Survivin
      function in spindle assembly.

PMID- 16888810
TI  - ERK 1/2 signaling pathway is involved in nicotine-mediated neuroprotection in
      spinal cord neurons.
AB  - Evidence indicates that agonists of neuronal nicotinic receptors (nAChRs),
      including nicotine, can induce neuroprotective and anti-apoptotic effects in the
      CNS. To study these mechanisms, the present study focused on nicotine-mediated
      modulation of the extracellular regulated kinase 1 and 2 (ERK1/2) pathway in
      cultured spinal cord neurons. Exposure to nicotine (0.1-10 microM) for as short
      as 1 min markedly upregulated levels of phosphorylated ERK1/2 (pERK1/2) and
      increased total ERK1/2 activity. Inhibition studies with mecamylamine and alpha
      bungarotoxin revealed that these effects were mediated by the alpha7 nicotinic
      receptor. In addition, pre-exposure to U0126, a specific inhibitor of the ERK1/2
      signaling, prevented nicotine-mediated anti-apoptotic effects. To indicate if
      treatment with nicotine also can activate ERK1/2 in vivo, a moderate spinal cord
      injury (SCI) was induced in rats using a weight-drop device and nicotine was
      injected 2 h post-trauma. Consistent with in vitro data, nicotine increased
      levels of pERK1/2 in this animal model of spinal cord trauma. Results of the
      present study indicate that the ERK1/2 pathway is involved in anti-apoptotic
      effects of nicotine in spinal cord neurons and may be involved in therapeutic
      effects of nicotine in spinal cord trauma.

PMID- 16888811
TI  - Extreme sensitivity to Yondelis (Trabectedin, ET-743) in low passaged sarcoma
      cell lines correlates with mutated p53.
AB  - Yondelis (Trabectedin, ET-743) is a marine anticancer agent currently in Phase
      II/III development in patients with advanced pretreated soft tissue sarcoma. In
      the present study, we generated a panel of low passaged tumor cell lines from
      samples explanted from chemonaive sarcoma patients with different tumor types. We
      assessed in vitro sensitivity/resistance to Trabectedin and doxorubicin in a
      panel of sarcoma cell lines and examined the correlation between molecular
      alterations in DNA repair genes and sensitivity to Trabectedin. We treated cell
      lines with Trabectedin and doxorubicin in both 96-h and clonogenic assays. In
      both assays, well-defined groups of resistant and sensitive cell lines were
      observed. Resistance to Trabectedin did not correlate with resistance to
      doxorubicin, indicating that the two drugs may have different mechanisms of
      resistance. p53 mutations and deletions correlated with extreme sensitivity (IC50
      < 1 nM) to Trabectedin (P < 0.01). In a pair of isogenic cell lines differing
      only in the presence or absence of wild-type p53, the absence of p53 rendered
      cells threefold more sensitive to Trabectedin.

PMID- 16888813
TI  - An effective method for adenoviral-mediated delivery of small interfering RNA
      into mesenchymal stem cells.
AB  - Mesenchymal stem cells (MSCs) promise as a main actor of cell-based therapeutic
      strategies, due to their intrinsic ability to differentiate along different
      mesenchymal cell lineages, able to repair the diseased or injured tissue in which
      they are localized. The application of MSCs in therapies requires an in depth
      knowledge of their biology and of the molecular mechanisms leading to MSC
      multilineage differentiation. The knockdown of target genes through small
      interfering RNA (siRNA) carried by adenoviruses (Ad) represents a valid tool for
      the study of the role of specific molecules in cell biology. Unfortunately, MSCs
      are poorly transfected by conventional Ad serotype 5 (Ad5) vectors. We set up a
      method to obtain a very efficient transduction of rat MSCs with low doses of
      unmodified Ad5, carrying the siRNA targeted against the mRNA coding for Rb2/p130
      (Ad-siRNA-Rb2), which plays a fundamental role in cell differentiation. This
      method allowed a 95% transduction rate of Ad-siRNA in MSC, along with a siRNA
      mediated 85% decrease of Rb2/p130 mRNA and a 70% decrease of Rb2/p130 protein 48
      h after transduction with 50 multiplicities of infection (MOIs) of Ad5. The
      effect on Rb2/p130 protein persisted 15 days after transduction. Finally, Ad
      siRNA did not compromise the viability of transduced MSCs neither induced any
      cell cycle modification. The effective Ad-siRNA-Rb2 we constructed, together with
      the efficient method of delivery in MSCs we set up, will allow an in depth
      analysis of the role of Rb2/p130 in MSC biology and multilineage differentiation.

PMID- 16888812
TI  - TGFbeta inducible early gene-1 (TIEG1) and cardiac hypertrophy: Discovery and
      characterization of a novel signaling pathway.
AB  - Cellular mechanisms causing cardiac hypertrophy are currently under intense
      investigation. We report a novel finding in the TGFbeta inducible early gene
      (TIEG) null mouse implicating TIEG1 in cardiac hypertrophy. The TIEG(-/-) knock
      out mouse was studied. Male mice age 4-16 months were characterized (N = 86
      total) using echocardiography, transcript profiling by gene microarray, and
      immunohistochemistry localized upregulated genes for determination of cellular
      mechanism. The female mice (N = 40) did not develop hypertrophy or fibrosis. The
      TIEG(-/-) knock-out mouse developed features of cardiac hypertrophy including
      asymmetric septal hypertrophy, an increase in ventricular size at age 16 months,
      an increase (214%) in mouse heart/weight body weight ratio TIEG(-/-), and an
      increase in wall thickness in TIEG(-/-) mice of (1.85 +/- 0.21 mm), compared to
      the control (1.13 +/- 0.15 mm, P < 0.04). Masson Trichrome staining demonstrated
      evidence of myocyte disarray and myofibroblast fibrosis. Microarray analysis of
      the left ventricles demonstrated that TIEG(-/-) heart tissues expressed a 13.81
      fold increase in pituitary tumor-transforming gene-1 (Pttg1). An increase in
      Pttg1 and histone H3 protein levels were confirmed in the TIEG(-/-) mice hearts
      tissues. We present evidence implicating TIEG and possibly its target gene,
      Pttg1, in the development of cardiac hypertrophy in the TIEG null mouse.

PMID- 16888814
TI  - Insulin-like growth factors induce apoptosis as well as proliferation in LIM 1215
      colon cancer cells.
AB  - The insulin-like growth factor (IGF) system plays an important role in cell
      proliferation and survival. However, more recently, a small number of studies
      have shown that IGFs induce apoptosis in some cells. Our initial studies showed
      this occurred in LIM 1215 colon cancer cells but not RD rhabdomyosarcoma cells.
      IGFs induced both proliferation and apoptosis in LIM 1215 cells, and the
      induction of apoptosis was dose-dependent. [R54, R55]IGF-II, which binds to the
      IGF-I receptor with normal affinity but does not bind to the IGF-II receptor,
      induced apoptosis to the same extent as IGF-II, whereas [L27]IGF-II, which binds
      to the IGF-I receptor with 1000-fold reduced affinity, had no effect on
      apoptosis. These results suggest that the IGF-I receptor is involved in induction
      of apoptosis. Western blot analyses demonstrated that Akt and Erk1/2 were
      constitutively activated in RD cells. In contrast, phosphorylation of Akt and
      Erk1/2 were transient and basal expression of Akt protein was lower in LIM 1215
      cells. Analysis of apoptosis-related proteins showed that IGFs decreased pro
      caspase-3 levels and increased expression of pro-apoptotic Bad in LIM 1215 cells.
      IGFs co-activate proliferative and apoptotic pathways in LIM 1215 cells, which
      may contribute to increased cell turnover. Since high turnover correlates with
      poor prognosis in colorectal cancer, this study provides further evidence for the
      role of the IGF system in its progression.

PMID- 16888815
TI  - In vitro differentiation of hepatic progenitor cells from mouse embryonic stem
      cells induced by sodium butyrate.
AB  - Recently it was shown that embryonic stem (ES) cells could differentiate into
      hepatocytes both in vitro and in vivo, however, prospective hepatic progenitor
      cells have not yet been isolated and characterized from ES cells. Here we
      presented a novel 4-step procedure for the differentiation of mouse ES cells into
      hepatic progenitor cells and then hepatocytes. The differentiated hepatocytes
      were identified by morphological, biochemical, and functional analyses. The
      hepatic progenitor cells were isolated from the cultures after the withdrawal of
      sodium butyrate, which was characterized by scant cytoplasm, ovoid nuclei, the
      ability of rapid proliferation, expression of a series of hepatic progenitor cell
      markers, and the potential of differentiation into hepatocytes and bile duct-like
      cells under the proper conditions that favor hepatocyte and bile epithelial
      differentiation. The differentiation of hepatocytes from hepatic progenitor cells
      was characterized by a number of hepatic cell markers including albumin
      secretion, upregulated transcription of glucose-6-phosphatase and tyrosine
      aminotransferase, and functional phenotypes such as glycogen storage. The results
      from our experiments demonstrated that ES cells could differentiate into a novel
      bipotential hepatic progenitor cell and mature into hepatocytes with typical
      morphological, phenotypic and functional characteristics, which provides an
      useful model for the studies of key events during early liver development and a
      potential source of transplantable cells for cell-replacement therapies.

PMID- 16888816
TI  - Mouse translation elongation factor eEF1A-2 interacts with Prdx-I to protect
      cells against apoptotic death induced by oxidative stress.
AB  - eEF1A-1 and eEF1A-2 are two isoforms of translation elongation factor eEF1A. In
      adult mammalian tissues, isoform eEF1A-1 is present in all tissues except
      neurons, cardiomyocytes, and myotubes, where its isoform, eEF1A-2, is the only
      form expressed. Both forms of eEF1A have been characterized to function in the
      protein elongation step of translation, and eEF1A-1 is shown to possess
      additional non-canonical roles in actin binding/bundling, microtubule
      bundling/severing, and cellular transformation processes. To study whether eEF1A
      2 has similar non-canonical functions, we carried out a yeast two-hybrid
      screening using a full sequence of mouse eEF1A-2 as bait. A total of 78 hits,
      representing 23 proteins, were identified and validated to be true positives. We
      have focused on the protein with the highest frequency of hits, peroxiredoxin I
      (Prdx-I), for in-depth study of its functional implication for eEF1A-2. Here we
      show that Prdx-I coimmunoprecipitates with eEF1A-2 from extracts of both cultured
      cells and mouse tissues expressing this protein, but it does not do so with its
      isoform, eEF1A-1, even though the latter is abundantly present. We also report
      that an eEF1A-2 and Prdx-I double transfectant increases resistance to peroxide
      induced cell death as high as 1 mM peroxide treatment, significantly higher than
      do single transfectants with either gene alone; this protection is correlated
      with reduced activation of caspases 3 and 8, and with increased expression of pro
      survival factor Akt. Thus, our results suggest that eEF1A-2 interacts with Prdx-I
      to functionally provide cells with extraordinary resistance to oxidative stress
      induced cell death.

PMID- 16888817
TI  - Chondrocyte apoptosis is not essential for cartilage calcification: evidence from
      an in vitro avian model.
AB  - The calcification of cartilage is an essential step in the process of normal bone
      growth through endochondral ossification. Chondrocyte apoptosis is generally
      observed prior to the transition of calcified cartilage to bone. There are,
      however, contradictory reports in the literature as to whether chondrocyte
      apoptosis is a precursor to cartilage calcification, a co-event, or occurs after
      calcification. The purpose of this study was to test the hypothesis that
      chondrocyte apoptosis is not a requirement for initial calcification using a cell
      culture system that mimics endochondral ossification. Mesenchymal stem cells
      harvested from Stages 21-23 chick limb buds were plated as micro-mass cultures in
      the presence of 4 mM inorganic phosphate (mineralizing conditions). The cultures
      were treated with either an apoptosis inhibitor or stimulator and compared to un
      treated controls before the start of calcification on day 7. Inhibition of
      apoptosis with the caspase inhibitor Z-Val-Ala-Asp (O-Me)-fluoromethylketone (Z
      VAD-fmk) caused no decreases in calcification as indicated by radioactive calcium
      uptake or Fourier transform infrared (FT-IR) analysis of mineral properties. When
      apoptosis was inhibited, the cultures showed more robust histological features
      (including more intense staining for proteoglycans, and more intact cells within
      the nodules as well as along the periphery of the cells as compared to untreated
      controls), more proliferation as noted by bromo-deoxyuridine (BrdU) labeling,
      decreases in terminal deoxynucleotidyl transferase (Tdt)-mediated dUTP nick-end
      labeling (TUNEL) staining, and fewer apoptotic bodies in electron microscopy.
      Stimulation of apoptosis with 40-120 nM staurosporine prior to the onset of
      calcification resulted in inhibition of calcium accretion, with the extent of
      total calcium uptake significantly decreased, the amount of matrix deposition
      impaired, and the formation of abnormal mineral crystals. These results indicate
      that chondrocyte apoptosis is not a pre-requisite for calcification in this
      culture system.

PMID- 16888819
TI  - Enantioselective total synthesis of (-)-acylfulvene and (-)-irofulven.

PMID- 16888818
TI  - Damage and recovery of the bone growth mechanism in young rats following 5
      fluorouracil acute chemotherapy.
AB  - Chemotherapy-induced bone growth arrest and osteoporosis are significant problems
      in paediatric cancer patients, and yet how chemotherapy affects bone growth
      remains unclear. This study characterised development and resolution of damage
      caused by acute chemotherapy with antimetabolite 5-fluorouracil (5-FU) in young
      rats in the growth plate cartilage and metaphyseal bone, two important tissues
      responsible for bone lengthening. In metaphysis, 5-FU induced apoptosis among
      osteoblasts and preosteoblasts on days 1-2. In growth plate, chondrocyte
      apoptosis appeared on days 5-10. Interestingly, Bax was induced prior to
      apoptosis and Bcl-2 was upregulated during recovery. 5-FU also suppressed cell
      proliferation on days 1-2. While proliferation returned to normal by day 3 in
      metaphysis, it recovered partially on day 3, overshot on days 5-7 and normalised
      by day 10 in growth plate. Histologically, growth plate heights decreased by days
      4-5 and returned normal by day 10. In metaphysis, primary spongiosa height was
      also reduced, mirroring changes in growth plate thickness. In metaphyseal
      secondary spongiosa, a reduced bone volume was observed on days 7-10 as there
      were fewer but more separated trabeculae. Starting from day 4, expression of some
      cartilage/bone matrix proteins and growth factors (TGF-beta1 and IGF-I) was
      increased. By day 14, cellular activity, histological structure and gene
      expression had returned normal in both tissues. Therefore, 5-FU chemotherapy
      affects bone growth directly by inducing apoptosis and inhibiting proliferation
      at growth plate cartilage and metaphyseal bone; after the acute damage, bone
      growth mechanism can recover, which is associated with upregulated expression of
      matrix proteins and growth factors.

PMID- 16888820
TI  - Gold(I)-catalyzed cyclizations of silyl enol ethers: application to the synthesis
      of (+)-lycopladine A.

PMID- 16888823
TI  - Highly efficient asymmetric michael addition of aldehydes to nitroalkenes
      catalyzed by a simple trans-4-hydroxyprolylamide.

PMID- 16888821
TI  - The case for cytomegalovirus prophylaxis in solid organ transplantation.
AB  - Cytomegalovirus prevention strategies have been debated for the past decade. This
      review argues in favour of the prophylaxis strategy. Clinical trials comparing
      prophylaxis to pre-emptive therapy have, thus far, had insufficient power to
      differentiate strategies, especially with regard to the indirect effects of CMV.
      From meta-analyses, prospective trials, observational studies, and case control
      studies, there is evidence that prophylaxis prevents cytomegalovirus infection
      and disease, reduces the indirect effects of cytomegalovirus, including organ
      rejection and transplant associated, all cause mortality as well as opportunistic
      infection, and even bacteremia as well as post transplant lymphoproliferative
      disease. Prophylaxis has also been shown to be cost effective. One must recognise
      that with the current prophylaxis regimens employed for 3 months post
      transplantation, late onset cases of cytomegalovirus disease may occur.
      Cytomegalovirus replication monitoring may be necessary after cessation of
      prophylaxis, especially in the high risk cytomegalovirus seropositive donor to
      cytomegalovirus seronegative recipient. Future trials with longer periods of
      prophylaxis are being undertaken.

PMID- 16888822
TI  - Enantioselective catalytic intramolecular cyclopropanation using modified
      cinchona alkaloid organocatalysts.

PMID- 16888824
TI  - The search for single DNA damage among millions of base pairs: DNA glycosylases
      trapped at work.

PMID- 16888825
TI  - Metallic magnesium nano/mesoscale structures: their shape-controlled preparation
      and mg/air battery applications.

PMID- 16888826
TI  - Manganese oxide nanoparticles electrodeposited on platinum are superior to
      platinum for oxygen reduction.

PMID- 16888827
TI  - Proton-fueled, reversible assembly of gold nanoparticles by controlled triplex
      formation.

PMID- 16888828
TI  - Metallic striped nanowires as multiplexed immunoassay platforms for pathogen
      detection.

PMID- 16888829
TI  - Radical-mediated alkenylation, alkynylation, methanimination, and cyanation of B
      alkylcatecholboranes.

PMID- 16888830
TI  - Storing and releasing hydrogen with a redox switch.

PMID- 16888831
TI  - beta-Disubstituted allylic chlorides: substrates for the Cu-catalyzed asymmetric
      SN2' reaction.

PMID- 16888832
TI  - Studies on iejimalide B: preparation of the seco acid and identification of the
      molecule's "Achilles heel".

PMID- 16888833
TI  - AIDS history research: new ArchiveGrid available.
AB  - A newly available online service allows anyone to locate private historical
      collections at more than 3,000 institutions, mostly in the U.S. A search for "ACT
      UP" found 61 collections of papers, videos, and other materials.

PMID- 16888834
TI  - Aphasia and leg weakness.

PMID- 16888835
TI  - Depression in the fly.

PMID- 16888837
TI  - Summary of the 2005 annual research and education meeting of the
      Spondyloarthritis Research and Therapy Network (SPARTAN).

PMID- 16888836
TI  - Passing potassium with and without gap junctions.

PMID- 16888838
TI  - Abstracts of the 30th Annual Meeting of the Society for the Study of
      Reproduction, July 29-August 1, 2006, Omaha, Nebraska, USA.

PMID- 16888839
TI  - Panamerican Congress of Spondyloarthropathies, Cartagena, Columbia, October 20
      22, 2005: Latin American rheumatology comes of age!

PMID- 16888840
TI  - Abstracts of the 6th European Conference on Health Economics without Frontiers,
      July 6-9, 2006, Budapest, Hungary.

PMID- 16888841
TI  - Balloon angioplasty or nitinol stents for peripheral-artery disease.

PMID- 16888842
TI  - Balloon angioplasty or nitinol stents for peripheral-artery disease.

PMID- 16888844
TI  - Abstracts of the National Osteoporosis Society 11th Conference on Osteoporosis,
      25-28 June 2006, Harrogate, United Kingdom.

PMID- 16888843
TI  - Balloon angioplasty or nitinol stents for peripheral-artery disease.

PMID- 16888845
TI  - Shattuck Lecture--medical education.

PMID- 16888846
TI  - Lineage-specific hematopoietic growth factors.

PMID- 16888848
TI  - Europerio 5, Madrid, Spain, 2006. Abstracts.

PMID- 16888847
TI  - Appraisal of treatment for severe sepsis in intensive care units.

PMID- 16888849
TI  - Renal research in Italy, directory of nephrology units.

PMID- 16888850
TI  - Glass behaviour: Poisson's ratio and liquid's fragility.
AB  - The lack of a reliable theory of glass physics has led to the pursuit of
      correlations between various glass or viscous liquid parameters, one of which is
      the slope m of the plot of log(viscosity) against Tg/T, extrapolated at the glass
      transition temperature, Tg, also termed 'fragility'. Novikov and Sokolov conclude
      that the value of m for a liquid varies linearly with the ratio of the
      instantaneous bulk and shear moduli, K infinity/G infinity, of its glass
      according to the relation m=29(K infinity/G infinity -0.41). Because of the
      obvious importance of the elastic properties of a glass, we have investigated the
      basis for this relation and find that its premise is flawed because of the
      unjustifiable preference for an empirical variation of m with elastic properties,
      and because of the selected use of glasses. When more glasses are considered in
      the same way, m does not seem to be linearly related to K infinity/G infinity.

PMID- 16888851
TI  - [What is the value of sports for young type 1 diabetics? (interview by Dr. Thomas
      Meissner)].

PMID- 16888852
TI  - [Can relaxation exercises calm the legs?].

PMID- 16888853
TI  - [Hormone substitution--a questionable IGeL indication].

PMID- 16888854
TI  - [Pathogenicity of bird flu virus H5N1].

PMID- 16888855
TI  - Limited life expectancy for the American health care system.

PMID- 16888856
TI  - What's to drink? Staying hydrated in the heat.

PMID- 16888858
TI  - Eating across America. New England specialties.

PMID- 16888857
TI  - Diabetes and your skin. Protecting your outermost layer.

PMID- 16888859
TI  - Antioxidants. Should you supplement?

PMID- 16888860
TI  - Treating foot ulcers. How a wound care center can help.

PMID- 16888861
TI  - Your diabetes management plan. Why it pays to have one.

PMID- 16888862
TI  - Supermarket smarts. Nuts, seeds, and nut butters.

PMID- 16888863
TI  - Diabetes resources. Travel tips.

PMID- 16888864
TI  - Diabetes quiz. How much do you know about blood glucose monitoring?

PMID- 16888865
TI  - Diabetes basics. Exenatide and pramlintide. New meds on the block.

PMID- 16888866
TI  - For parents. School's out! Adjusting to summer.

PMID- 16888867
TI  - Dyspepsia and its overlap with irritable bowel syndrome.
AB  - Patients with functional dyspepsia and the irritable bowel syndrome are commonly
      seen in both primary care and gastroenterology subspecialty settings. Although
      functional dyspepsia and the irritable bowel syndrome can occur separately,
      recent research suggests that they often appear together as an overlap syndrome
      and thus may represent different portions of a unifying spectrum of disease.
      Despite their widespread prevalence, the pathogenesis of these disorders is not
      well established but may include impaired gastric emptying, gastric dysrhythmias,
      hypersensitivity (to acid exposure and to stretch), and Helicobacter pylori
      infection. Once other disorders in the differential diagnosis have been excluded,
      treatment of patients with functional dyspepsia, irritable bowel syndrome, and
      the overlap syndrome without alarm signs underscores current prevailing
      pathophysiologies and is generally empiric and symptom based. It is hoped that
      management of these disorders will become more targeted and efficacious as our
      understanding of them improves.

PMID- 16888868
TI  - Irritable bowel syndrome: update on colonic neuromuscular dysfunction and
      treatment.
AB  - Recent discoveries regarding the relatively autonomous workings of the enteric
      nervous system have expanded our understanding of the pathophysiology of
      irritable bowel syndrome (IBS). However, the heterogeneity of the pathogenesis of
      IBS continues to create unique challenges for clinicians who care for these
      patients. Advances in our understanding of the structure and functions of the
      brain-gut axis and its interplay with other potentially important factors, such
      as genetic predisposition, inflammation, and psychological unrest, have led to
      new developments in the field of targeted pharmacotherapy for IBS sufferers.
      Therapies designed specifically to modulate gut motility, secretion, and/or
      sensation have been created and introduced into the marketplace in recent years,
      and additional designer formulations are in various stages of development.
      Concurrently, new discoveries of potentially beneficial effects of agents
      approved for other, often non-gastroenterologic, conditions continue to be
      reported. This article reviews the accumulating body of evidence supporting the
      importance of neuromuscular dysfunction as a central cause of IBS symptoms and
      provides a rationale for the discussion of current and future drug development.

PMID- 16888869
TI  - Irritable bowel syndrome and chronic constipation: emerging drugs, devices, and
      surgical treatments.
AB  - Irritable bowel syndrome (IBS) and chronic constipation (CC) are two of the most
      common functional disorders of the gut. CC and IBS are estimated to affect up to
      20% and 27% of the North American population respectively. Although not life
      threatening, CC and IBS can profoundly and negatively affect quality of life and
      are associated with a significant economic burden related to direct and indirect
      annual health-care costs. Possible etiologies for IBS and CC include alterations
      in visceral sensation and gastrointestinal motility. IBS may be caused by
      disturbances in brain-gut interactions affecting gastrointestinal motility and
      visceral sensitivity. Research efforts in CC have begun to identify abnormalities
      in myenteric neurons, alterations in neurotransmitters and their receptors, and
      incoordination of the muscles of the pelvic floor or anorectum. Both disorders
      may be influenced by genetic predisposition, environmental factors, and stress.
      In this article, the safety and efficacy of traditional and emerging therapies
      for CC and IBS are examined. In addition, their pathophysiology and symptoms are
      briefly reviewed.

PMID- 16888870
TI  - Defecation disorders: neuromuscular aspects and treatment.
AB  - Chronic constipation and fecal incontinence affect 20% of the population and are
      more prevalent in women, the elderly, those of lower socioeconomic status, and
      nursing home residents. These disorders pose a significant economic burden and
      affect quality of life. During the past decade, significant strides have been
      made in the understanding and treatment of defecation disorders, which have led
      to real advances in the management of these disorders. These treatments include
      biofeedback therapy, tegaserod, and lubiprostone for chronic constipation.

PMID- 16888873
TI  - Cholera 2005.

PMID- 16888874
TI  - AIDS treatment enters its 25th year.

PMID- 16888875
TI  - South African methamphetamine boom could fuel further HIV.

PMID- 16888876
TI  - Influenza pandemic vaccines: how to ensure a low-cost, low-dose option.

PMID- 16888877
TI  - Faecal matters.

PMID- 16888878
TI  - Novel finding in yeast gives insight into neurofibromatosis.

PMID- 16888879
TI  - Notice of redundant publication. About the paper "Plasma levels of interleukin-18
      and interleukin-12 in Plasmodium falciparum malaria" by Lucia Malaguarnera,
      Salvatore Pignatelli, Jacques Simpore, Mariano Malaguarnera and Salvatore
      Musumeci, from Department of Pediatrics, Sassari, Italy.

PMID- 16888880
TI  - No time to lose.

PMID- 16888881
TI  - Is competition good for care?

PMID- 16888882
TI  - Use of autogenous bone graft from the iliac crest to restore an atrophic maxilla
      with implant-retained prosthesis.

PMID- 16888884
TI  - Researchers identify genes that allow oral bacteria to infect arteries.

PMID- 16888883
TI  - How can I tell if a patient has obstructive sleep apnea?

PMID- 16888885
TI  - What are the roles of surgery, radiation therapy and chemotherapy in the
      treatment of  oral cancer?

PMID- 16888886
TI  - Can an impacted mandibular third molar be removed in a way that prevents 
      subsequent formation of a periodontal pocket behind the second molar?

PMID- 16888887
TI  - A 25-year-old woman presents for treatment with a chipped front tooth and a black
      eye. Should I ask about domestic violence and, if it is occurring, what should I
      do?

PMID- 16888888
TI  - Role of the Indian Medical Association (IMA) in polio eradication.

PMID- 16888889
TI  - Is a peaceful coexistence possible in health care?

PMID- 16888890
TI  - Seeking to understand case management in New York.

PMID- 16888891
TI  - [Pathology in Bamberg].

PMID- 16888892
TI  - [Classification and differential diagnosis of B-cell lymphomas].
AB  - The standard for the pathological identification of B-cell lymphomas is the World
      Health Organization (WHO) classification, which integrates tumor morphology,
      immunophenotype, recurrent genetic abnormalities and clinical features. The
      lymphoma entities defined in this classification are derived from virtually every
      stage of normal B-cell differentiation. This classification which has gained wide
      acceptance has proven useful in patient management and treatment. Novel findings
      based on gene expression profiling have however started to reveal that not all
      described entities are entirely molecularly homogeneous. This report describes
      distinct examples of the more common B-cell lymphomas along with the pathogenetic
      models and gives some information on the novel gene expression profiling data.

PMID- 16888872
TI  - Long-term follow-up of patients receiving lung-volume-reduction surgery versus
      medical therapy for severe emphysema by the National Emphysema Treatment Trial
      Research Group.
AB  - BACKGROUND: The National Emphysema Treatment Trial defined subgroups of patients
      with severe emphysema in whom lung-volume-reduction surgery (LVRS) improved
      survival and function at 2 years. Two additional years of follow-up provide
      valuable information regarding durability. METHODS: A total of 1218 patients with
      severe emphysema were randomized to receive LVRS or medical treatment. We present
      updated analyses (4.3 versus 2.4 years median follow-up), including 40% more
      patients with functional measures 2 years after randomization. RESULTS: The
      intention-to-treat analysis of 1218 randomized patients demonstrates an overall
      survival advantage for LVRS, with a 5-year risk ratio (RR) for death of 0.86 (p =
      0.02). Improvement was more likely in the LVRS than in the medical group for
      maximal exercise through 3 years and for health-related quality of life (St.
      George's Respiratory Questionnaire [SGRQ]) through 4 years. Updated comparisons
      of survival and functional improvement were consistent with initial results for
      four clinical subgroups of non-high-risk patients defined by upper-lobe
      predominance and exercise capacity. After LVRS, the upper-lobe patients with low
      exercise capacity demonstrated improved survival (5-year RR, 0.67; p = 0.003),
      exercise throughout 3 years (p < 0.001), and symptoms (SGRQ) through 5 years (p <
      0.001 years 1 to 3, p = 0.01 year 5). Upper-lobe-predominant and high-exercise
      capacity LVRS patients obtained no survival advantage but were likely to improve
      exercise capacity (p < 0.01 years 1 to 3) and SGRQ (p < 0.01 years 1 to 4).
      CONCLUSIONS: Effects of LVRS are durable, and it can be recommended for upper
      lobe-predominant emphysema patients with low exercise capacity and should be
      considered for palliation in patients with upper-lobe emphysema and high exercise
      capacity.

PMID- 16888893
TI  - [Classification and differential diagnosis of NK/T-cell lymphomas].
AB  - The first classifications deviding B- and T-cell lymphomas were given with the
      Kiel classification and in the classification of Lukes and Collins. Those
      entities first described like T-zone lymphomas or T-CLL are the rarest types of
      the known entities today. The updated Kiel classification contained a large
      number of especially nodal peripheral T-cell lymphomas and seperated
      lymphoblastic ones from those which derive from peripheral T-cells. The
      increasing knowledge on T-cell differentiation allowed a more detailed
      description of entities according either to their primary organ manifestation
      (subcutaneous panniculitis-like T-cell lymphoma), their immunophenotype (NK/T
      cell lymphomas with expression of CD56) or their rearrangement of the T-cell
      receptor (predominantly gamma/sigma-rearrangement in hepatosplenic T-cell
      lymphoma). The today's nodal and extranodal NK/T-cell lymphoma entities are
      summarized by the WHO classification. They can be seperated in primary leukemic
      ones, primary nodal ones, primary extranodal and primary cutaneous ones. In
      extranodal sites some lymphoma entities show a characteristic picture which is
      unique for this localisation. It has become clear that morphology alone is not
      able to lead to a reproducable classification of T-cell lymphomas. Today
      immunhistochemistry together with the distinct primary organ localisation are the
      major tools for classifying peripheral NK/T-cell lymphomas. In this paper
      distinct examples which are interesting in the differential diagnosis or which
      are distinct clinico-pathological entities are described. Moreover, an indication
      is given on some new rare entities which have not yet been listed in the WHO
      classification.

PMID- 16888894
TI  - [Pathology of Hodgkin's lymphoma].
AB  - Hodgkin's lymphoma can be divided with the help of morphologic and
      immunohistochemical techniques into classical and nodular lymphocyte predominant
      Hodgkin's lymphoma. By single cell analyses it could be established that the
      tumor cells of Hodgkin's lymphoma are clonal B-cells with germinal center origin.
      In rare cases (less than 5 %), the Hodgkin and Reed Sternberg cells represent
      clonal tumor cells that derive from T-cells. By gene expression analyses it can
      be shown that Hodgkin cell lines represent an entity independently of their B- or
      T-cell-origin. Hodgkin cell lines show similarities to EBV transformed B-cells
      and in vitro activated B-cells. The genes found with the help of gene expression
      analyses may have crucial importance in the pathogenesis and are potentially new
      diagnostic markers and therapeutic targets.

PMID- 16888895
TI  - [25 years of the German Study Group of Hodgkin's Disease--a successful
      cooperation of pathologists and clinicians].

PMID- 16888896
TI  - Acute leukemia: subtype discovery and prediction of outcome by gene expression
      profiling.
AB  - Contemporary treatment of acute leukemia requires the accurate assignment of
      patients at diagnosis to specific risk groups. To determine whether gene
      expression profiling could enhance risk assignment, we used oligonucleotide
      microarrays to analyze the pattern of genes expressed in leukemic blasts from 360
      pediatric ALL patients and 130 pediatric AML patients. Our analysis demonstrates
      that the single platform of gene expression profiling can accurately identify the
      known prognostically important genetic subtypes of ALL, including T-ALL, E2A
      PBX1, TEL-AML1, MLL rearrangements, BCR-abl, and hyperdiploid >50 chromosomes,
      and AML, including t(15;17)[PML-RARalpha], t(8;21)[AML1-ETO], inv(16)[CBFbeta
      MYH11], MLL gene rearrangement, and cases with FAB-M7 morphology. In addition,
      within ALL, a novel subgroup was identified based on its unique expression
      profile. Examination of the gene expression signatures for the different genetic
      subtypes of acute leukemia provided important insights into the molecular
      pathology of these leukemias.

PMID- 16888897
TI  - New insights into the biology of acute myeloid leukemia and their impact on
      treatment.
AB  - Acute myeloid leukemia (AML) is a heterogeneous group of disorders that can be
      discriminated by morphology, immunophenotyping or more recently by cytogenetic
      and molecular techniques. By cytogenetics two major groups of AML can be
      discriminated: One group with detectable chromosomal aberrations accounting for
      approximately 52 % of all de novo AML and the second group without
      cytogenetically detectable karyotype abnormalities. In the first group two major
      subtypes can be further distinguished. The first group comprises AML with
      balanced aberrations mainly consisting in t(8;21), t(15;17) and inv(16). The
      second group comprizes cases with unbalanced aberrations including particularly
      5q-, 17q- -5 and AML with complex karyotypes. AMLs with balanced aberrations have
      a good prognosis with long term survival being achieved in approximately 60 %-80
      % of cases. AMLs with non-balanced aberrations on the other hand have a poor
      prognosis with only 10 %-15 % long-term survivors. AMLs with no detectable
      abnormalities or other cytogenetic aberrations comprise a group with an
      intermediate prognosis in which long term survival is achieved in approximately
      25 %-30 % of cases. Biologically, AMLs with balanced aberrations regularly
      involve the deregulation of transcription factors resulting in an impairment of
      cell differentiation and proliferation. AMLs with unbalanced aberrations are
      mostly characterized by a loss of genetic material resulting in an alteration of
      cell cycle control and DNA repair. A new view on the biology of AML has recently
      been made possible through the analysis of gene expression profiles. This
      technique is still under investigation. First results, however, already show that
      gene expression patterns have a high diagnostic potential and allow to detect
      biology subgroups with a high accuracy. Furthermore, by this technique pathways
      can be identified that are altered in the leukemic process. Gene expression
      profiling therefore opens a new and exciting perspective in leukemia biology and
      therapy that may have substantial impact on the improvement of diagnosis and more
      importantly may guide therapeutic strategies.

PMID- 16888898
TI  - The pathogenetic significance of deregulated signal transduction pathways in
      Hodgkin's disease: the NF-kappaB-AP-1 network.
AB  - In the recent years, progress has been made in defining the lineage origin of
      malignant cells of Hodgkin's disease. The use of single cell PCR analysis and of
      other molecular probes has allowed to determine that the malignant Hodgkin/Reed
      Sternberg cells correspond mostly to a post germinal center stage of normal B
      lymphocyte development. However, the agents which cause primary transformation
      events are still unknown. A comprehensive analysis of dysregulated signaling
      pathways in H/RS-cells with a focus on inducible and lymphoid-specific
      transcription factors has provided an independent approach to characterize
      molecular lesions, which may account for the tumorigenicity of H/RS-cells.
      Transcription factors of the NF-kappaB and AP-1 multigene families could be
      identified as crucial mediators of both, cell cycle promoting and cell-death
      inhibiting pathways in H/RS-cells. High level activity of these regulators has
      multifarious consequences for the gene expression repertoire of H/RS-cells, as
      has been revealed by large scale gene profiling. The dissection of the molecular
      mechanisms which constitutively activate NF-kappaB and AP-1 may help to gain
      further insight into the pathogenesis of Hodgkin's disease and may provide novel
      targets for pharmacological intervention.

PMID- 16888899
TI  - Shaping up adaptive immunity: the impact of CCR7 and CXCR5 on lymphocyte
      trafficking.
AB  - The effective onset of adaptive immune responses requires that naive antigen
      specific lymphocytes, being inherently rare throughout the body, rapidly
      encounter foreign antigens. This problem has been elegantly solved in evolution
      by inventing secondary lymphoid tissues as intersections in the migratory pathway
      of antigen-presenting dendritic cells and antigen-specific lymphocytes.
      Chemokines play a central role in guiding cell movements in the course of immune
      responses and in lymphoid system homeostasis. In particular, the chemokine
      receptors CCR7 and CXCR5 are key molecules for the entry of lymphocytes and
      dendritic cells into secondary lymphoid organs and their homing to T-cell and B
      cell zones therein. CCR7 and CXCR5 are differentially expressed on the cell
      surface of lymphocytes and dendritic cells depending of the stage of cellular
      differentiation and activation, thus allowing these cells to change their homing
      capacity and prospective traffic routes.

PMID- 16888901
TI  - [Lymphocytic proliferation in gastric mucosa].
AB  - There is the substantial problem as how to exactly define the minimal
      requirements for the diagnosis of a marginal zone B cell lymphoma of MALT type in
      the stomach. Consequently, there is vigorous disagreement in the literature
      whether or not clonal B cell proliferation exists in chronic gastritis. This
      situation was the starting point of a retrospective multicenter study of
      German/Swiss lymph node registries. The panel contributed gastric biopsies of 26
      cases of consensually diagnosed gastric marginal zone lymphoma, 18 borderline
      cases and 53 cases of consensually diagnosed chronic gastritis. The Wotherspoon
      criteria were used and were found very appropriate in conjunction with CD20
      immunohistology highlighting lymphoepithelial lesions. The gastritis cases scored
      Wotherspoon 1 or 2, the borderline cases 3 or 4, the lymphomas 5. Extensive PCR
      analysis, carried out independently at two institutions using two methodologies,
      revealed, 1., an excellent interinstitutional accordance in detection of
      clonality; 2., B cell clonality in 24/26 lymphoma cases, 4/18 borderline cases,
      and in 1/53 gastritis cases. Thus, "clonal gastritis", if existing at all, is
      exceedingly rare. Based on Wotherspoon criteria, the proposal is to define and
      proclaim a state of "B cell clonality of unknown significance, BCUS" for clonal
      cases scoring less than 5. "BCUS" should induce re-biopsies, and, in this special
      clinical setting, justifies a wachfull waiting strategy. Further, the problem of
      coexisting diffuse large B cell lymphoma in gastric MALT lymphoma is addressed
      and discussed. It is demonstrated why the panel dismissed the de Jong criteria as
      non-applicable in praxi.

PMID- 16888900
TI  - Clonality and malignancy. PCR assays for the diagnosis of clonal B- and T-cell
      proliferations: potentials and pitfalls.
AB  - The discrimination between lymphomas and reactive lymphoproliferations is
      difficult or even impossible in a proportion of cases by means of histology and
      additional immunhistochemistry alone. Therefore, the analysis of the clonality of
      the rearranged immunoglobulin genes and T-cell receptor genes, respectively, is
      often employed as an additional diagnostic tool. This analysis is based on the
      fact that the tumor cells of lymphomas harbor identically (clonally) rearranged
      antigen receptor genes whereas reactive lymphoproliferations consist of cells
      with differently (polyclonally or oligoclonally) rearranged antigen receptor
      genes. Initially Southern blot analysis was used to determine the presence of
      clonal lymphoid cell populations. Meanwhile polymerase chain reaction (PCR) is
      the method of choice because of its higher sensitivity and its applicability to
      DNA extracted from formalin-fixed tissues. Although this PCR approach appears to
      be simple, there are many pitfalls, which can lead to false negative or false
      positive results. In a diagnostic setting, these false clonality results could
      give rise to a wrong final diagnosis and, as a consequence, to the performance of
      an inadequate therapy. The reasons for the non-detectability of clonal B-cell or
      T-cell populations or for the detection of false clonality (e.g. clonal
      rearrangement pattern in the absence of a lymphoma) are manifold. In the
      following the most frequent reasons are discussed and recommendations are given
      to avoid false negative and false positive results.

PMID- 16888902
TI  - Gastric lymphomas: genetics and resistance to H. pylori eradication.
AB  - Gastric mucosa associated lymphoid tissue (MALT) lymphoma is a histologically
      distinct tumour derived from MALT acquired as a result of Helicobacter pylori
      infection. Eradication of H. pylori causes clinical regression of the lymphoma n
      75 % of cases. In seeking to identify those cases resistant to this therapy, and
      in the interests of further understanding the biology of MALT lymphoma, genetic
      alterations of MALT lymphomas have been investigated. Three translocations,
      t(11;18)(q21; q21), t(1;14)(p22;q32) and t(14;18)(q32;q21) are specifically
      associated with MALT lymphoma and the genes involved have been identified.
      T(11;18) results in a chimeric fusion between the API2 and MALT1 genes and is
      specifically associated with gastric MALT lymphomas that do not respond to
      eradication of H. pylori. T(1; 14) and t(14; 18) deregulate bcl-10 and MALT1
      expression respectively. These three chromosomal translocations that involve
      different genes appear to share common oncogenic properties by targeting the to
      target the same NFkappaB oncogenic pathway.

PMID- 16888903
TI  - [Molecular carcinogenesis of the upper gastrointestinal tract].
AB  - Carcinomas of the upper gastrointestinal tract have been intensively studied for
      decades in order to identify markers for a) design of simple blood tests to
      detect presence or recurrence of the disease, b) prediction of therapy response,
      c) identification of molecular targets for novel therapies. These aims have not
      yet been fully reached by analysing single genes. However, some genes, including
      E-cadherin that is altered in sporadic and familial cases of gastric cancer and
      interleukin 1-beta whose polymorphisms together with Helicobacter pylori
      infection are associated with an increased risk for gastric cancer, may have the
      potential for clinical use. In this review we summarize current data for the
      single gene approach and provide an overview for recent results from cDNA
      microarray studies.

PMID- 16888904
TI  - [Early carcinomas of the upper gastrointestinal tract: diagnostic problems].
AB  - Problems arising when diagnosing biopsy material from the upper gastrointestinal
      tract are encountered in particular with changes that might minic a carcinoma. In
      the squamous epithelium of the oesophagus, such problem lesions are viral
      infections, regenerative changes in reflux disease, and pseudoepitheliomatous
      hyperplasia in subepithelial lesion. In Barrett's mucosa, regenerative changes
      are often overdiagnosed as low grade dysplasia, and will-differentiated
      adenocarcinomas underdiagnosed as high grade dysplasia. In the stomach, the
      regenerative mucosa at the margins of erosions and ulcers--in particular in the
      case of NSAID/ASA-induced lesions--is the most common cause of the wrong
      diagnosis of carcinoma. Such misdiagnoses can usually be avoided by taking
      careful account of the endoscopic findings. In the case of doubt, a second
      pathological opinion, an extensive endoscopy/biopsy follow-up examination (after
      treatment), or a diagnostic endoscopic mucosectomy, is to be recommended.

PMID- 16888906
TI  - [Molecular cytopathology of lung cancer--prevalence of genetic alterations and
      their role in the development of molecular biomarkers].
AB  - Carcinogenesis of lung cancer proceeds via a complex process that involves
      multiple genetic abnormalities, which do not necessarily have a linear
      progression. Genetic alterations include aneuploidy, deletions and amplifications
      of chromosomal regions, loss of heterozygosity (LOH), microsatellite alterations,
      point mutations and aberrant promoter methylation. There is considerable effort
      to use these genetic alterations as molecular biomarkers for early cancer
      diagnosis applying different approaches. An ideal tumor marker should be highly
      sensitive, tumor specific, easily to handle and non-cost intensive. While
      previous studies used screening for mutations, LOH and microsatellite
      alterations, more recent strategies concentrate on multicolor fluorescence in
      situ hybridization (FISH) and aberrant promoter methylation. Since in general the
      genetic alterations are prone to be more extensive in tumor cells as compared to
      non-tumor cells, methods that provide quantitative data (e.g., methylation
      specific real-time PCR) are likely to improve specificity. Consequently,
      molecular biomarkers could constribute to a more accurate risk assessment in
      carcinogen exposed individuals and early molecular cytologic diagnosis of
      precancerous lesions and cancers of the lung.

PMID- 16888905
TI  - [Diagnosis and therapy of early neoplasia in Barrett's esophagus].
AB  - There has been a dramatic increase in recent years in the incidence of Barrett's
      esophagus and the esophageal adenocarcinoma associated with it. Adequate
      monitoring strategies and improved diagnostic procedures are therefore essential.
      Alongside conventional video endoscopy with four-quadrant biopsies, many
      additional diagnostic procedures are now available to improve monitoring. These
      allow early diagnosis of dysplastic areas and early carcinomas. Endoscopic
      therapy has gained more and more importance in the treatment of early esophageal
      neoplasias over the last few years. Localized lesions in the Barrett's segment
      should be treated by endoscopic resection (ER). Only in patients with not
      localized or multifocal superficial lesions photodynamic therapy (PDT) should be
      used. Between the different ER techniques the "suck and cut"-technique with
      ligation device or cap should be favoured to normal strip biopsy in the esophagus
      because of the size of the resected specimen and its technical feasibility. ER of
      high grade intraepithelial neoplasia and mucosal adenocarcinoma in Barrett's
      esophagus should be considered as the treatment of choice. ER of early neoplasia
      in Barrett's esophagus is a safe and effective method but should only be
      performed by experienced endoscopists.

PMID- 16888907
TI  - ["Politics is nothing else than large scale medicine"--Rudolf Virchow and his
      role in the development of social medicine].

PMID- 16888908
TI  - [From single disseminated tumor cells to metastasis insights from molecular
      genetic analyses of single cells].
AB  - The prevailing models of cancer metastasis postulate that, after a series of
      accumulating genetic and epigenetic changes during transformation and invasive
      growth, the most advanced clone within a primary tumour acquires the critical
      cellular phenotype enabling dissemination and metastasis. This postulate is
      particularly based on observations that metastases usually display more genetic
      changes than the primary tumour. The development of several novel techniques is
      now enabling experimental testing of the model: The detection of single
      disseminated cancer cells by epithelial specific antibodies directed against
      cytokeratin in mesenchymal tissues has become possible even before manifestation
      of metastasis. After their isolation by micromanipulation comprehensive
      amplification of the single cell genomes allows the application of several
      molecular genetic methods for further characterisation. Our first data from
      single cytokeratin-positive cells that were isolated from the bone marrow of
      breast cancer patients indicate that the model of cancer progression should be
      revised. Cancer cells already disseminate in an early stage of genomic
      development and still have to acquire the critical chromosomal aberrations needed
      for metastatic outgrowth and full malignant potential. These observations
      apparently imply consequences for the development of novel adjuvant therapies.
      The early diversification of primary tumours and disseminated cancer cells
      precludes a simple extrapolation from local to systemic disease eventually
      necessitating increasing efforts for the direct analysis of single disseminated
      cancer cells as the cellular targets of adjuvant therapies.

PMID- 16888909
TI  - [A new dimension of DNA analysis: genomic profiling by matrix CGH].
AB  - Analysis of genetic alterations in tumor cells represent a first step to
      understand the molecular mechanism of cancer etiology and development. Due to the
      progress in genome research, it is feasible to assess the complexity of genomic
      changes on a large scale. Protocols for gene expression profiling using cDNA
      arrays have been developed allowing to test the activity of almost all human
      genes in tumor cells. Another important approach is matrix-CGH which was recently
      developed to assess gains and losses on the genomic level with high resolution.
      This method not only allows to narrow down the position of novel oncogenes or
      tumor suppressor-genes but also contributes to a refinement of tumor
      classifications. Since matrix-CGH can be performed under highly standardized
      conditions in a fully automatized way, it is suited for diagnostics in clinical
      laboratories.

PMID- 16888910
TI  - [Molecular changes in development and progression of urothelial carcinoma].
AB  - The multistep development of malignant tumors with increasing accumulation of
      genetic alterations from preneoplastic lesions to invasive carcinoma is an
      accepted model of carcinogenesis. Urothelial carcinoma of the bladder and upper
      urinary tract is an interesting model system to study tumor development and
      progression. There is both clinical and molecular evidence that urothelial
      carcinoma can be divided in two groups with different characteristics: 1) well
      differentiated genetic stable and mostly superficial papillary tumors with
      frequent recurrence and low progression risk and 2) poorly differentiated mostly
      solid and invasive tumors with a high number of genetic alterations. The aim of
      the studies summarized in this manuscript were: 1) to identify genetic changes
      with importance for urothelial carcinogenesis by investigation of preneoplastic
      and early neoplastic urothelial lesions, 2) to define molecular markers for
      progression of papillary carcinoma, and 3) to investigate the importance of
      microsatellite instability and mismatch repair defects for development of tumors
      of the upper urinary tract which are frequently found within the HNPCC syndrome.
      The investigation of urothelial hyperplasias, dysplasias and carcinoma in situ by
      deletion mapping (LOH analysis), FISH, CGH and mutation detection revealed that
      urothelial hyperplasias are precursors of papillary bladder tumors and flat
      dysplasias can be regarded as precursors of solid bladder cancers. In bladder
      cancer patients, there are genetic alterations already detectable in
      histologically inconspicous urothelium. The investigation of papillary bladder
      cancers for progression-related genetic alterations showed that mutations in the
      wnt pathway genes APC and beta-Catenin do not play an important role in
      urothelial carcinogenesis. Instead, the expression of the antagonistic wnt
      related genes WIF-1 and sFRPI is strongly reduced in bladder cancer and
      associated with poor prognosis in papillary tumors. Loss of sFRP1 expression is
      not due to gene mutation but to epigenetic inactivation by promoter
      hypermethylation and is related to deletions at chromosome 8p12. In contrast to
      bladder cancers, tumors of the ureter and renal pelvis develop through a
      different genetic pathway in 30% of cases. The loss of mismatch repair proteins
      (hMSH2, hMLH1 or hMSH6) leads to a mutator phenotype with accumulation of genetic
      alterations in multiple repetitive sequences (microsatellite instability, MSI).
      MSI-positive tumors were predominantly located in the ureter and showed a lower
      tumor stage and grade and papillary and frequently inverted growth pattern. They
      were more frequent in females and younger patients and had a higher incidence of
      colorectal carcinomas and other tumors in the family. Chromosome 9 deletions, a
      hallmark of urothelial carcinomas, and the number of chromosomal alterations as
      detected by CGH analysis were significantly less frequent in these tumors. These
      data strongly suggest a distinct molecular pathway in the development of upper
      urinary tract tumors with mutator phenotype.

PMID- 16888911
TI  - [Differential gene expression signatures in well differentiated thyroid
      carcinomas].
AB  - Despite their common origin from follicular epithelial cells, papillary and
      follicular thyroid carcinomas differ in their histology and clinical course. In
      this study the transcriptional profiles of these tumors in comparison with normal
      thyroid tissue were established. The aim was the development of a molecular tool
      providing additional information to current histopathological diagnosis and
      allowing further insight into tumorigenesis. Genome wide expression profiling was
      performed using Human Unigene Set--RZPD 2 high density cDNA macroarrays
      comprising 76,000 genes as probes and radioactively labeled cDNA targets
      retrotranscribed from the isolated RNA of three papillary and three follicular
      thyroid carcinomas as well as three normal thyroid tissues. 8600 genes differing
      in their expression between the three groups were selected and printed onto
      subarrays. Radioactively labeled cDNA targets obtained from 16 papillary
      carcinomas, 13 follicular carcinomas and 17 normal thyroid tissues were
      hybridized to these subarrays. 200 genes exhibited a statistically significant
      expression difference between the two tumor types (p <0.01). In a hierarchical
      cluster analysis of 124 of these genes (46 known genes and 78 ESTs) the algorythm
      divided the tumor samples into two groups corresponding to the papillary and
      follicular thyroid carcinomas. The clearcut diagnostic potential of this method
      has to be corroborated in a prospective study. Several of the differentiallly
      expressed genes are known to play a role in tumor development and metastasis.
      Some of the genes up- or down-regulated in both tumor types are members of known
      oncogenic pathways in thyroid carcinomas. The complete understanding of complex
      genome wide expression profiles however awaits a longstanding advancement of
      hypothesis driven research.

PMID- 16888912
TI  - Mathematical tree models for cytogenetic development in solid tumors.
AB  - We present a new approach for modeling the occurrence of genetic changes in human
      tumors over time. In solid tumors, data on genetic alterations are usually only
      available at a single point in time, allowing no direct insight into the
      sequential order of genetic events. In our approach, genetic tumor development
      and progression is assumed to follow a probabilistic tree model. We use maximum
      likelihood estimation to reconstruct a tree model for the genetic evolution of a
      given tumor type. The use of the proposed method is illustrated by an application
      to cytogenetic data from 173 cases of clear cell renal cell carcinoma, which
      results in a model for the karyotypic evolution of this tumor.

PMID- 16888913
TI  - Secretory carcinoma of the breast: a genetically defined carcinoma entity.
AB  - Secretory carcinomas (SBC) are characterized by their characteristic
      histomorphology and more favorable prognosis compared to invasive ductal
      carcinoma of usual type (IDC). On this basis, 13 SBCs are evaluated by molecular
      and immunohistochemical (IH) methods. 13 SBCs and 4 IDCs were analyzed for ETV6
      NTRK3 gene fusion by reverse transcriptase-polymerase chain reaction (RT-PCR) and
      by Fluorescence in situ Hybridization (FISH). 8 of 13 microdissected SBCs with
      evaluable DNA were evaluated for genetic alterations (GA) by comparative genomic
      hybridization (CGH). IH included estrogen-receptor (ER), progesterone-receptor
      (PR), Her-2/neu and Ki-67 (MIB-1) in all 13 cases. Molecular and
      immunohistochemical results in SBCs were compared with previous data regarding
      immunohistochemical and molecular characteristics of IDCs. 12 of 13 (92 %) SBC
      cases, but not IDCs expressed the ETV6-NTRK3 fusion gene which encodes a chimeric
      tyrosine kinase. Retroviral transfer of ETV6-NTRK3 (EN) into murine mammary
      epithelial cells resulted in transformed cells that readily formed epithelial
      tumors in nude mice. CGH revealed an average of 2.0 GAs (range 0-6), including
      recurrent gains of chromosome 8q and 1q and losses of 22q. Four SBCs were
      positive for ER and 2 were positive for PR. The mean MIB-1-labeling index was
      11.4% (range: <1-34%). Her-2/ neu protein overexpression was detected in 1 case
      (score 3+). Compared to previous findings in IDCs, SBCs are characterized by the
      recurrent expression of ETV6-NTRK3 fusion gene, a relatively low number of GAs,
      low proliferative rate, infrequent Her-2/ neu protein overexpression and a lower
      rate of steroid hormone receptor expression. These results support the hypothesis
      that SBCs have immunohistochemical and genetic features that specifically
      distinguish them from IDCs.

PMID- 16888914
TI  - [Differential gene expression in the wear particle induced and infectious
      periprosthetic membrane of loosened knee-endoprostheses].
AB  - About 5 to 12 % of hip endoprostheses will loosen after ten years. The
      periprosthetic membran between bone and prosthesis plays a crucial role in
      prosthesis loosening. Different pathomechanisms lead to the growth of such a
      membran, which can be discriminated by different histomorphologies: wear particle
      induced type, infectious type, combined type, indifferent type. 8 hybridizations
      were performed on PIQOR cDNA arrays. Objects of the study were periprosthetic
      interface tissue samples from 3 patients with particle induced and 2 patients
      with infectious prosthesis loosening. Tissue parts directly adjacent to the site
      of RNA-isolation were analyzed immuno-/ histopathologically in order to overcome
      the problem of tissue heterogeneity. 34 genes were found constantly
      differentially expressed, among which were cd9, cd11b, cd18, cd68, osteopontin,
      ferritin heavy-chain upregulated in the particle induced membrane and collagen
      types 1alpha-1, 3alpha-1, integrin alpha-1, thrombospondin 2 and nidogen
      upregulated in the infectious membrane. The most striking finding was the strong
      upregulation (from 20 fold to 323 fold) of megakaryocyte stimulating factor (msf)
      in all wear particle cases and 1 out of 2 infectious cases, which was confirmed
      by real-time RT-PCR. The upregulation of msf suggests an important pathogenetic
      role: The msf splice product lubricin is responsible for the lubrification of
      healthy joints, but its excellent lubrification ability may disturb the tight
      interaction between bone and prosthesis and thereby contribute to prosthesis
      loosening.

PMID- 16888916
TI  - [Overexpression of NPM-ALK induces different types of malignant lymphomas in IL-9
      transgenic mice].
AB  - Anaplastic large cell lymphoma (ALCL) comprises approximately 25 % of all non
      Hodgkin lymphomas in children and young adults. 40% of these tumours have a
      translocation t(2;5)(p23;q35), which fuses the nucleophosmin gene (NPM) to the
      anaplastic lymphoma kinase gene (ALK) resulting in a hybrid protein which
      contributes to the pathogenensis of ALCL. To further analyse the transforming
      activity in an animal model, a cDNA encoding the protein product, NPM-ALK, was
      incorporated into a retrovirus construct and introduced into mouse bone marrow
      progenitors by infection. In a bone marrow gene transfer and transplantation
      protocol the hematopoietic compartments of lethally irradiated IL-9 transgenic
      mice were reconstituted with npm-alk infected progenitor cells. IL-9 transgenic
      mice were chosen, because IL-9, a pleiotropic T helper 2 cytokine, is expressed
      in most cases of human ALCL and was shown to have an oncogenic potential at least
      on T cells. Reconstituted mice developed NPM-ALK positive lymphomas including
      lymphoblastic lymphomas of T-cell type (T-LB), mature and immature plasmacytoma
      (PZ) and plasmoblastic/anaplastic diffuse large B-cell lymphoma after 10-30
      weeks. The combined overexpression of NPM-ALK and IL-9 exerts cooperative
      oncogenic activity in the transformation of murine lymphoid cells leading to
      accelerated and enhanced development of T-LB. Many animals developed
      plasmacytic/plasmoblastic neoplasms, of which the most aggressive tumours share
      many features with human anaplastic/plasmoblastic diffuse large B-cell lymphoma.

PMID- 16888915
TI  - [The "classical" macrophage marker CD68 is strongly expressed in primary human
      fibroblasts].
AB  - AIM: Monoclonal antibodies against the human homologue of mouse macrosialin,
      CD68, are generally commercialized as markers for human monocytes and
      macrophages. Indeed, CD68 is considered as a selective marker for human myeloid
      cells, although several previous immunohistochemical studies indicate that some
      antibody clones also react with other hematopoietic and non-hematopoietic cell
      types. The aim of our study was to verify these observations and to evaluate the
      reliability of CD68 as a macrophage marker. METHODS: We investigated protein and
      RNA expression of CD68 in various fibroblast types and carcinoma cell lines as
      compared to monocytes and macrophages using immunohistochemistry, flow cytometry,
      and specific RT-PCR. Different monoclonal antibody clones against CD68 were
      applied including KP-1 and EBM11. RESULTS: As expected, the intensity of
      immunohistochemical and flow cytometric CD68 staining was dependent on both the
      antibody clone and the fixation procedure. However, fibroblasts isolated from
      normal skin, normal breast, breast tumor tissue, and osteoarthritis synovia
      clearly expressed CD68 protein at levels comparable to macrophages. The
      specificity of CD68 expression in fibroblasts was verified by RT-PCR which also
      showed some tumor cell types to express CD68 mRNA. CONCLUSION: Our findings
      clearly demonstrate that the expression of CD68 is not restricted to the
      macrophage lineage. This is highly relevant for experimental and diagnostic
      purposes, since anti CD68 antibodies cannot be accepted without reservations for
      the discrimination of myeloid cells and fibroblasts even in paraffin sections
      after formalin fixation.

PMID- 16888918
TI  - [List of member. German Society for Pathology].

PMID- 16888917
TI  - [Autocrine stimulation of receptor-tyrosine kinases (RTK) in human tumor cell
      lines in vitro: therapeutic implications].
AB  - AIMS: The VEGF/VEGFR system is known to play an important role in the development
      of new blood vessels during tumor formation. There is evidence that VEGFRs are
      not only present on endothelial cells but also on tumor cells. Since VEGF is able
      to induce proliferation and migration via VEGFR-2 we have studied the expression
      of VEGFRs and related receptor tyrosine kinases (RTKs) in different tumor cell
      lines and the effect of growth factor stimulation. METHODS: RTK expression was
      investigated in 5 different human tumor cell lines on protein and mRNA levels.
      Tumor cell lines were exposed to growth factors such as VEGF and the
      phosphorylation of downstream molecules involved in proliferation, migration and
      apoptosis were assessed. Under comparable conditions proliferation and migration
      essays were performed. Endogenous production of VEGF and PDGF by the tumor cells
      was measured by ELISA of cell culture supernatants. RESULTS: Most tested cell
      lines expressed all known VEGFR's, PDGFR-beta on protein and mRNA levels to a
      varying extent. 3 out of 5 cell lines could be stimulated after addition of VEGF
      reflected by an increased phosphorylation of MAPK, AKT/PKB and to a lesser extent
      of p38. This was underlined by an increased cell number and reduced number of
      apoptotic cells. After stimulation with PDGF-BB a stronger induction of MAPK and
      AKT/PKB phosphorylation than for VEGF could be seen. In contrast, no effect on
      tumor cell migration was detectable in all examined cell lines. The investigation
      of cell culture supernatants revealed that most cell lines do not produce VEGF or
      PDGF. CONCLUSIONS: Tumor cell lines express RTKs and the receptor is stimulable
      after addition of growth factors such as VEGF. Thus, secretion of groth factors
      in the tumor microenvironment is not only able to stimulate proliferation and
      survival of endothelial cells but also tumor cells themselve. One cell line
      displayed high levels of endogenous VEGF which could explain the lack of an
      increased cell number after addition of VEGF. It remains obscure why another cell
      line could not be stimulated although receptors were present at the cellular
      surface. Further investigations should prove that RTK's could be influenced by
      therapeutic drugs in order to suppress cell proliferation and migration and
      induce apoptosis in tumor cell lines.

PMID- 16888919
TI  - [Botulism in cattle].
AB  - Botulism is an intoxication caused by ingestion of feed or water contaminated
      with the toxin of Clostridium botulinum. In cattle, intoxication usually results
      from the ingestion of feed containing preformed type C or D toxin, either in feed
      which has been contaminated with toxin-containing carcasses or in feed in which
      there has been primary multiplication of C. botulinum and toxin production. The
      initial signs of botulism are progressive difficulty in chewing and swallowing,
      caused by paralysis of the tongue and muscles of mastication. This results in
      slow prehension and chewing of feed, water and feed falling out of the mouth,
      excessive salivation and weakness of the tongue. After 1 to 3 days, generalised
      paralysis occurs followed by death due to respiratory paralysis. Intravenous
      fluid therapy is the recommended treatment. The administration of antiserum is of
      limited value in advanced stages and is used mainly as a prophylactic measure in
      cattle herds in which an outbreak has just started. Active immunization of cattle
      in high-risk herds is also an option. It is critical that cattle not be fed feed
      contaminated with soil or carcasses.

PMID- 16888920
TI  - [TSE surveillance in small ruminants and pigs: a pilot study].
AB  - Switzerland is controlling Transmissible Spongiform Encephalopathies (TSE) in
      cattle (BSE) and small ruminants (scrapie). Since BSE is potentially
      transmissible to sheep, goats or pigs through feeding of contaminated meat and
      bone meal, implementation of an active surveillance programme for TSE in these
      species is discussed. The aim of this pilot study was to obtain preliminary data
      on the prevalence ofTSE and other neurological disorders in these populations.
      For that purpose, a total of 398 perished and 825 slaughtered adult small
      ruminants and pigs was examined for the presence of neuropathological changes.
      None of these animals revealed positive for TSE. However, the investigations
      demonstrated that perished sheep and goats exhibited a higher prevalence of
      relevant neuropathological changes when compared with slaughtered animals. From
      these results, it is concluded that perished small ruminants are probably a risk
      population for TSE and should be considered as target populations for an active
      surveillance programme.

PMID- 16888921
TI  - [Retrospective evaluation of the results of the microbiological meat examination
      (MFU) from calves and cows].
AB  - The microbiological meat examination (MFU), consisting of a bacteriological
      analysis and a testing for antibiotic residues, is one of several additional
      analyses used for an edibility rating of carcasses made during meat inspection.
      Reasons for performing a microbiological meat examination and procedures in the
      laboratory are defined in the Swiss ordinance for meat examination (FUV). The aim
      of this study was to analyze the data of 313 microbiological meat examinations
      from calves and 2882 microbiological meat examinations from cows carried out at
      the Institute for Food Safety and Hygiene during a period of 8 years. Reasons for
      microbiological meat examinations as reported by the meat inspectors were mainly
      classified to the category of "inflammation and necroses" (FUV, Annex 4, Pt 1.2;
      calves: 73%, cows: 48%). As declarations of the age of the pathological
      anatomical changes (that influences directly the probability of detection of
      pathogens) were generally missing, it is not surprising that the compliance
      between a particular pathological-anatomical change and a specific detection of
      pathogens is poor (calves: 19%, cows: 18% of all MFU). About 18% (calves) and 45%
      (cows) of the reasons for microbiological meat examinations did not correspond to
      one of the reasons mentioned in the ordinance for meat examination. However,
      according to the data set, some reasons require a microbiological meat
      examination due to an often-found specific detection of pathogens. Otherwise, a
      remarkable number of reasons mentioned were missing the link to bacteriological
      etiology. Moreover, 14% (calf) and 7% (cow) of microbiological meat examinations
      with the declaration "no pretreatment" as well as 15% (calf) and 11% (cow) of
      microbiological meat examinations without declaration showed a positive result in
      the testing for antibiotic residues.

PMID- 16888922
TI  - Observations and immunohistochemical detection of Coronavirus, Cryptosporidium
      parvum and Giardia intestinalis in neonatal diarrhoea in lambs and kids.
AB  - In this study, clinical, parasitological, macroscopical, histopathological and
      immunohistochemical examinations were performed on 19 kids and 11 lambs (30
      animals) with neonatal diarrhoea to detect the presence of Coronavirus,
      Cryptosporidium parvum and Giardia intestinalis. Clinically, severe dehydration,
      yellowish-green to brown coloured diarrhoea and death were observed. Mortality
      rates were 10-30% in the examined flocks. The most common agent was C. parvum
      diagnosed in 20 animals as a single causative agent, whereas G. intestinalis was
      found in 5 of 30 animals. These two protozoa were detected together in 4 animals
      upon faeces examination. Fifteen of 24 cases of C. parvum and 3 of 11 cases of G.
      intestinalis were also confirmed histopathologically. Following
      immunohistochemical examination, all cryptosporidiosis cases were confirmed by
      positive immunostaining of intestinal sections. Two additional Giardiosis cases
      with negative results upon parasitological and histopathological examinations
      were diagnosed by means of immunohistochemical examination. Coronavirus was
      detected immunohistochemically in one kid with neonatal enteritis. Following
      diagnosis, herds were treated with Trimethoprim + Sulfodoxine and multivitamin
      complexes. Intravenous and intramuscular administrations of these drugs were
      effective for both treatment and prevention of neonatal diarrhoea in lambs and
      kids.

PMID- 16888923
TI  - [Arterial hypertension. 4. Pregnancy-induced hypertension].

PMID- 16888924
TI  - [Accidental hypothermia: an extreme case of successful resuscitation].
AB  - This case involved a 65-year-old male with severe hypothermia who presented a
      cardiorespiratory arrest on his arrival in hospital. He was treated by means of a
      cardiopulmonary bypass and subsequently made good recovery. In this article we
      summarise the signs and symptoms of hypothermia, the treatment of a patient with
      hypothermia and the different rewarming strategies, based on the current
      literature on the subject.

PMID- 16888925
TI  - [ECTS--33rd European Symposium on Calcified Tissues].

PMID- 16888926
TI  - [A 25-year-old woman with fever and hepatosplenomegaly: diagnostic approach].
AB  - We proceeded to an extensive etiologic search in a young women with a
      hepatosplenomegaly and a chronic persistent fever. We discuss the differential
      diagnosis of this situation with a final diagnosis of sarcoidosis.

PMID- 16888927
TI  - [FOSAVANCE -- alendronate plus vitamin D in a weekly tablet].

PMID- 16888928
TI  - [Cerebellar abscess--unusual reason for ataxia in an alcoholic patient].
AB  - A 45-year-old alcoholic man showing an acute ataxia followed by a central
      respiratory arrest caused by multiple cerebellar abscesses is hospitalised. We
      describe here a differential diagnosis of an acute ataxia as well as the cerebral
      abscess mechanisms and causes.

PMID- 16888929
TI  - [Spontaneous hemoperitoneum: diagnosis, prognosis and possible therapeutics].
AB  - We report the case of a 58-year-old diabetic man admitted to the hospital in a
      comatose state due to medicamentous hypoglycemia in a context of hypovolemic
      acute renal failure. Hypovolemia was due to hemoperitoneum in a alcoholic patient
      with cirrhotic hepatic failure. CT-scan and arterial angiographies revealed a
      voluminous isolated hepatic mass with active bleeding suggesting the diagnosis of
      spontaneous bleeding from a hepatocellular carcinoma. The hemorrhage resolved
      after selective arterial embolization, but the patient died two weeks later from
      an infectious cause. The differential diagnosis of a spontaneous hemoperitoneum
      and possibilities of treatment in the case of ruptured hepatocellular carcinoma
      are discussed.

PMID- 16888930
TI  - [Is the parasite fauna of Poland well recognized?].
AB  - The studies of parasite fauna have in Poland a long tradition. Generally the
      helmint fauna of all groups of vertebrates was more or less examined and as much
      as over 100 species of Monogenea, almost 400 Digenea, over 250 Cestoda, about 500
      Nematoda and 32 Acanthocephala have been recorded. The best recognized are the
      helminths of fish (especially those of Cyprinidae, Esocidae, Percidae and
      Salmonidae), frogs examined in various regions of Poland, some birds (especially
      connected with water environment: Anseriformes, Ciconiformes, Podicipediformes),
      most of insectivores (although examined only in few localities), European bisons,
      deers, foxes and wild boars (all under permanent monitoring), as well as domestic
      animals (cattle, horses, sheeps) and pets. Such groups like some amphibians,
      reptiles, bats, carniwores, some birds (especially Passeriformes,
      Charadriiformes, falcons and eagles) need further exploration, as some host
      species were not the subject of parasitological investigation. In some cases it
      will be rather difficult goal, as most of these animals are under strict
      preservation, and only dead (naturally or accidentally) specimens can be
      autopsied.

PMID- 16888931
TI  - [Faunistics--the science of XIX or XXI age?].
AB  - Rapid development of modern research techniques which has exploded in the second
      half of 20th century supressed interest in faunistic research. On the other hand
      the negative impact of human activity on the biosphere caused the need of
      intensification of the biodiversity studies. Several international and regional
      programs were founded to gather data about all species living in Europe and other
      continents. They also emphasize the importance of the faunistic researches that
      comprise studies on nature of parasite fauna (description of species, their
      morphology, variability, life cycles). Since faunistics and systematics are
      regain their weight, they are becoming the important area of twenty first century
      research.

PMID- 16888932
TI  - [Resistance in the hematophagous arthropods--problem on the rise. I. Resistance
      mechanisms to insecticides].
AB  - Hematophagous arthropods are pesky but can also be very dangerous to human health
      due to their ability to act as vectors to many viral, bacterial or parasite
      related diseases. The common application of chemicals to control pests leaded to
      the increasing resistance to pesticides among both insects and ticks. The causes
      underlying the appearance of the resistance and the mechanisms involved are
      presented in this article. The description of mechanisms is presented starting
      from decreased penetration of the pesticide, to an increase in metabolism of
      pesticide, to the reduced sensitivity of the pesticide's target.

PMID- 16888933
TI  - [50 anniversary of the Commitee on Parasitology of the Polish Academy of
      Sciences].

PMID- 16888935
TI  - The activity of hydrolases of entomopathogenic nematodes.
AB  - Similar patterns of hydrolases were observed in three species representing two
      genera of entomopathogenic nematodes: Steinernema affinis, S. feltiae, and
      Heterorhabditis zealandica. The same enzymes were present in the studied
      nematodes but they differed in the level of activity of individual sub-classes of
      enzymes. A higher activity of esterases and proteolytic enzymes could be observed
      for H. zealandica than for S. affinis and S. feltiae. On the other hand, the
      activity of glycosidases in steinernematids was generally much higher than in H.
      zealandica.

PMID- 16888934
TI  - [Biodiversity of mycocoenoses of oral cavity, throat and nose of children aged 6
      15 years].
AB  - The purpose of this study was analysis of biodiversity of mycoflora in selected
      ontocenoses of healthy children. The material for the study was consisted of
      swabs taken from oral cavity, pharynx, and nose of healthy children: 128 girls
      and 142 boys. The material for the study was collected in May and November,
      dividing the children into two age groups: 6-9 years and 10-15 years. A total of
      13 species representing 5 genera: Candida, Rhodotorula, Saccharomyces,
      Saccharomycopsis and Trichosporon were found in the material studied. The
      dominant group were yeasts-like fungi. Candida albicans, the basic etiological
      factor of the majority of mycotic diseases in humans, was found most frequently.
      Appearance of Candida glabrata and C. krusei is a reason for concern, as
      increasing numbers of their strains are resistant to basic antimycotic drugs, as
      well as relatively frequent appearance of Trichosporon beigelii, Saccharomycopsis
      capsularis, and Saccharomyces sp.--the fungi showing increasing expansiveness and
      enzymatic activity. The fungi were most frequently isolated from oral cavity and
      pharynx. No phenological changes in fungal prevalence were found in the pharynx.
      In the other ontocenoses fungi were found much more frequently in the spring than
      in the autumn. Regardless of the season, the largest fluctuations in biodiversity
      and numbers of the studied mycocoenoses were observed in the oral cavity and nose
      -the organs that come into direct contact with environmental contaminants and
      many agents of transmission for potentially pathological fungi.

PMID- 16888936
TI  - [Joint Conference of The 42nd Clinical Day of Medical Parasitology & VIIIth
      Polish National Symposium "Ecology of the Contemporary Man". "Environmental
      Conditions of Parasitic Diseases and Mycoses, and other Ecological Issues"].

PMID- 16888937
TI  - [What is going on in the International Commission of Trichinellosis].

PMID- 16888938
TI  - [Parasites as a natural element of any ecosystem].
AB  - The article presents some ideas upon the functioning of the parasite populations
      and communities in relation to the whole ecosystem. The author underlines that
      the parasites are one of the natural elements of every biocenosis and their
      existence submittes to similar ecological rules as the populations and
      communities of free-living organisms. Colonization of their particular
      environment (living organism) demands some adaptations allowing to resist
      immunological defense of the host, and to coexist with other parasite species
      harboured by the same host, not exploiting the supplies over the host "carying
      capacity", what could provoke the strong pathogenic effects, including host
      death. The mechanims maintaning the state of relative stability in host-parasite
      system are similar as in the case of free-living organisms, and are of both
      parasite- and host origin. They can confine the number of parasites (elimination
      of some specimens) or their biomass (growth restraint), limit their fecundity
      (maturation restraint), or make particular species to use different supply
      (niches separation). On the other hand parasite can regulate the demography of
      host population: restrict their fecundity, or kill their host directly or
      indirectly (making them an easier prey for predators). The author presents and
      discusses some examples illustrating the activity of the regulating mechanisms in
      host-parasite relationship, as well as the role of parasites in energetic
      ballance of ecosystem and in "engineering of ecosystem".

PMID- 16888939
TI  - [Strongyloidosis. Part VIII. Parasitological diagnosis].
AB  - The effectiveness and safety of the methods of detecting Strongyloides
      stercoralis, by passing larvae from the faeces to water, in duodenal fluid
      (duodenal intubation, Enterotest), in sputum and other body fluids, have been
      estimated. The author recommend Baermann technique for detecting S. stercoralis
      in individual examinations and Dancescu technique in mass field examinations. The
      detection of S. stercoralis larvae by the two methods ought to be checked by
      Fulleborn agar Petri dish technique in order to identify parasite to the species
      level.

PMID- 16888940
TI  - [Strongyloidosis. Part IX. Treatment].
AB  - The treatment of chronic and massive (uncomplicated) and severe (complicated)
      disseminated strongyloidosis, was presented from the historical point of view.
      The sequence of achievements in regard of treatment of the gentian violet,
      dithiazine iodide, benzimidazoles (thiabendazole, mebendazole, albendazole,
      cambendazole), ivermectin and cyclosporin A, was described. The recommendations
      for treatment of strongyloidosis are also given.

PMID- 16888941
TI  - Colonization of the round goby, Neogobius melanostomus (Gobiidae) by parasites in
      the new environment of the Gulf of Gdansk (Southern Baltic).
AB  - The round goby (Neogobius melanostomus) is a non-indigenous species in the Baltic
      Sea, introduced to its waters (the Gulf of Gdansk) from the Black, Azov, and
      Caspian Seas. For this reason, an attempt was made to determine the species'
      parasitic fauna in its new environment. Within 1994-2000, a total of 201 round
      goby specimens caught in the Gulf of Gdansk were examined. The parasites found
      represented protozoans (Trichodina domerguei domerguei), digeneans (Diplostomum
      spp. metacercariae), cestodes (Bothriocephalus scorpii, plerocercoids), nematodes
      (Hysterothylacium aduncum L3, L4, and adults), and acanthocephalans
      (Echinorhynchus gadi and Pomphorhynchus laevis). The parasitic species found are
      common in the Gulf of Gdansk. It should be emphasized that, since the round goby
      has only recently appeared in the Gulf, the parasitic fauna of this fish is not
      yet complete.

PMID- 16888942
TI  - [The occurrence of Ixodes ricinus in the selected recreative areas in the
      province of Szczecin. Part III].
AB  - Within the last years, the incidences of diseases transmitted by Ixodes ricinus
      tick have rapidly increased. We estimated the occurrence of Ixodes ricinus in the
      popular recreation urban areas in Szczecin and in the Province of Szczecin. The
      study was carried out in 1999, with two samples at each site, and were compared
      with data of 1998. The temperature and humidity of air were measured. The most
      ticks were found in the range of 70-80% relative humidity of air. Among 3.198
      specimens collected 59.5% were nymphs, 19.0% larvae, 11.1% females and 10.4%
      males. The nymphs were the most frequent in spring and in autumn, while the
      larvae were most frequent in autumn (26.2%) then in spring (11.9%).

PMID- 16888943
TI  - Parasite fauna of selected fish species of Lake Miedwie.
AB  - A total of 136 fishes, representing 9 species (perch, Perca fluviatilis L.; pike,
      Esox lucius L.; European eel, Anguilla anguilla (L.); common bream, Abramis brama
      (L.); roach, Rutilus rutilus (L.); tench Tinca tinca (L.); European whitefish,
      Coregonus lavaretus (L.); vendace, Coregonus albula (L.); and zander, Sander
      lucioperca (L.)), from Lake Miedwie were studied within 1997-1999. The necropsies
      yielded 41 parasite species (taxa). The most diversified were parasite faunas of
      pike (19 parasite species) and perch (16 species). The parasites found
      represented 13 higher taxa: Monera, Fungi, Protista, Myxozoa, Monogenea, Cestoda,
      Digenea, Nematoda, Acanthocephala, Branchiura, Copepoda, Mollusca, and Acarina.
      The parasites affecting fishes of Lake Miedwie exhibited diversified host
      specificity. The most fish species were infected by metacercariae of Diplostomum
      spp. (8 fish species) and Tylodelphys clavata (7). Three fish species harboured:
      Ichthyocotylurus platycephalus, Ergasilus sieboldi, and glochidia Unionidae gen.
      sp. while Dermocystidium sp., Trichodinella epizootica, Henneguya psorospermica,
      Triaenophorus nodulosus, Posthodiplostomum cuticula, and Camallanus lacustris
      parasitised two host species. The remaining parasites were found in single fish
      species.

PMID- 16888944
TI  - Influence of Anisakis simplex stage III larvae upon the activity of proteases
      under in vitro conditions.
AB  - The larvae of Anisakis simplex had the largest influence upon decreasing the
      activity of porcine pepsin. The activity of that enzyme in tests, where the
      larvae were present during the entire period of incubation, was lower than in the
      controls. No similar trends were observed in case of the solutions with bovine
      and porcine trypsin. The activity of those enzymes in the solutions containing
      the larvae was higher than in the controls. Only the activity of porcine trypsin
      after 10 h of incubation was slightly lower in the experimental sample than in
      the control, however, during the later hours the dynamics of the activity
      decrease of that enzyme in the controls was higher than in the experimental
      samples. The recorded activity of papain in the samples containing the larvae was
      higher than that in the controls during the entire time of the experiment.

PMID- 16888945
TI  - [The influence of Fasciola hepatica invasion on the assorted milk quality
      parameters in cows].
AB  - The investigations of the influence of Fasciola hepatica invasion on the assorted
      parameters of milk quality were performed in cows. Mean protein content in the
      milk from infected animals ammounted 3.60% and was higher than in the milk from
      uninfected cows (3.30%). Similar tendency was observed in the case of the fat
      (5.08% and 3.91%) and lactose (4.36% and 4.34%). The count of somatic cells in
      milk from infected cows was lower than in milk from uninfected animals (356.07
      and 1776.92). It can indicate immunosupressive activity of Fasciola hepatica on
      the host.

PMID- 16888946
TI  - [Role of gastropods in epidemiology of human parasitic diseases].
AB  - Pulmonate and prosobranch snails, being necessary hosts for parthenogenetic
      generations of digenetic trematodes, participate in transmission of all
      trematodoses important from medical point of view. Role of particular gastropods
      in epidemiology of these diseases is discussed in details. Invasion of land
      snails and slugs is mainly passive by eggs containing developed miracidia, while
      enter of these larvae into snails inhabiting fresh-water environments is usually
      active. Generations in the snail host between miracidia and cercariae vary
      considerable, depending upon the fluke species. Generally, the cercaria is
      produced by the sporocyst or the redia. Cercariae usually actively penetrate out
      of the infected snail and enter water. Leaving out of account cases of
      encystation of cercariae in external environment (liver flukes of the family
      Fasciolidae) and active penetration into the final host (blood flukes of the
      family Schistosomatidae), encystation of these larvae takes place in the second
      intermediate host. Cercariae of medically important flukes may develop into
      metacercariae in tissues of fish (liver flukes - Opisthorchis felineus,
      Clonorchis sinensis, intestinal flukes--Heterophyes heterophyes, Metagonimus
      yokogawai, Troglotrema salmincola), as well as in crustaceans (pulmonary flukes
      of the genus Paragonimus), insects (the bipathogenic liver fluke Dicrocoelium
      dendriticum and other species of the family Plagiorchiidae incidentally found in
      man), and gastropods (flukes of the family Echinostomatidae, among them perhaps
      the best known is the Oriental species--Echinostoma ilocanum). In prevention and
      control of human trematodoses, especially in endemic foci, elimination of snail
      hosts is a great importance. Using molluscides may be objectionable from the
      stadpoint of environmental modification through their toxicity to other
      organisms. Biological control of snail hosts is more attractive. It includes
      introduction and management of predators, parasites, or pathogens, and
      intramolluscan competition. Moreover, certain slugs and terrestrial snails
      participate in transmission of nematode larval stages, including species known as
      pathogenic for man - the strongylid nematodes of the genus Angiostrongylus). Such
      infections may be prevented by abstanding from eating raw or inadequately cooked
      molluscs in endemic areas.

PMID- 16888948
TI  - Bloodsucking arthropods: the danger for travellers and hazard of vector
      travelling.
AB  - The newly obtained data supplemented our knowledge about risk for travellers,
      tourists and natives of Europe connected with malaria, leishmaniasis and other
      tropical diseases. It was discovered that healthy carriers of Epstein-Barr virus
      (nearly 90% of human population) have a great risk to get chronic Burkitt
      lymphoma disease as a result of Plasmodium falciparum (tropical malaria agent)
      infection. HIV carriers being occasionally in contact with visceral leishmaniasis
      vectors (sand-flies infected on dogs in the Mediterranean area) not only got a
      heavy form of disease but became a source of infection for healthy people.
      Airport malaria and outbreaks of dengue fever sometimes were (and are) connected
      with an import of infective Anopheles or Aedes mosquitoes. The high risk of
      borreliosis and ehrlichiosis infection exists in the forested European areas
      along the highways, where picnics and other types of recreation of travellers and
      tourists are typical and where the anthropogenically changed Ixodes ticks
      subpopulations are distributed. Such physiologically changed part of tick
      population is more aggressive and "changed ticks" more often are vectors of one,
      two or even more agent species simultaneously.

PMID- 16888947
TI  - [Predacious nematode-destroying fungi].
AB  - Gastrointestinal nematodes are considered a serious economic problem affecting
      the livestock industry around the world. Current methods of their control,
      relaying mainly on organic drugs, are not sustainable because parasites develop
      resistance to anthelmintic and bacause of increasing public concern about
      chemicals residues in livestock products and environment. Nematode-trapping fungi
      offer a very promissing, nonchemotherapeutic approach to nematode parasite
      control. Their potential in preventing nematodosis is well documented. In this
      paper we outline the present knowlege on mechanisms involved in trapping and
      killing nematodes by the predacious nematode-destroying fungi.

PMID- 16888950
TI  - Occurrence of Trichodina pediculus Ehrenberg, 1838 in Dgal Wielki Lake.
AB  - Parasitological investigation were performed in Dgal Wielki, occurrence T.
      pediculus Ehrenberg 1838 on the roach gills were recorded. On the 277 examined
      roach in 9 roach specimens T. pediculus were found. Prevalence of roach infection
      was 3.25%, mean intensity 3.5 and abundance 0.11 parasite per number of fish
      examined. T. pediculus were found on fish in May and June.

PMID- 16888949
TI  - [Trials of penetration modification by inflammatory infiltrating cells into
      Trichinella spiralis larva capsules].
AB  - The inflammatory infiltration cells penetrating through the larval capsule walls
      were observed. The observation were carried out in the masseter muscle of the
      mice infected with Trichinella spiralis larvae only (control) or infected and
      treated with PHA-P, TFX or dexamethason. The more numerous cells, than in the
      control, in the mice treated with PHA-P and TFX were seen. Opposite, the fever
      numerous cells inside the capsula walls in the mice that received dexamethason
      were found. The authors supposed that the phenomenon of inflammatory cells
      penetration through larval capsule play an important role in the defence
      mechanisms of the host.

PMID- 16888951
TI  - Seasonal dynamics of Ceratophyllus sciurorum sciurorum (Schrank, 1803)
      (Siphonaptera) in Slovakia.
AB  - The authors pay attention to an occurrence of the taxon Ceratophyllus sciurorum
      sciurorum (Schrank, 1803) (Siphonaptera) in Slovakia during the whole season. The
      curve of occurrence this taxon of fleas has showed two high points. The first top
      has been achieved in April and second one followed in October. In December the
      authors have noticed a period and named it "cocoon block". This course of the
      curve has been found at the species from family Myoxidae, mostly. On the other
      hand, the course of curve of the birdboxes nesters has the opossite position, the
      high points have been recorded in autumn. A conspicuous differences has been
      probably caused by different biology of nesters of Myoxidae and birds in boxes.
      The ratio of males to females these ecological groups of hosts was different,
      too.

PMID- 16888953
TI  - [Dynamics of infestation of the Lipoptena cervi (L.) (Diptera, Hippoboscidae)
      with the fallow deer from Pomerania].
AB  - In yers 1996 - 2000 fallow deer were examined in the area of north-western part
      of Poland (Pomeranian Lakeland). 295 fallow deer were examined and Lipoptena
      cervi was found on 220 of them; the prevalence was 75%, intensity ca 9.9
      individuals.

PMID- 16888952
TI  - [Argas reflexus (Fabricius, 1794) as a cause of acarosis in people].
AB  - The studies were carried out between 1997-1999 within the administrative district
      of Torun. Forty sports pigeon breeders together with their pigeonswere understudy
      annually. The collected material allowed noticing the following issues: in 1997
      and 1998 the Argas reflexus (Fabricius, 1794) was present in dovecotes
      (individuals) and t he breeds' owners were pricked. In 1998 numerous specimens of
      the A. reflexus were obtained from the material from the sanitary-epidemiological
      station. The specimens were collected from the bodies of the people, family
      members and from their flat located on the highest third floor of the old house.
      In the mite-infected dovecotes and in the old houserooms, the following steps
      were suggested: mechanical cleansing, whitewashing, disinfecting, and triple
      disinsecting, with fourteen-day-long intervals. The people with the symptoms of
      acariosis were subjected to treatment with calcium, anti-allergic, and anti-fever
      mixtures, and, in some cases, cortisone ointments were applied. In spite of a
      considerable growth in the symptoms, the used methods turned out to be successful
      in all the studied cases.

PMID- 16888955
TI  - Position, structure and function of pulsatile vesicles in parasitic leeches
      Codonobdella truncata Grube, 1873 and Caspiobdella fadejewi Epshtein, 1961
      (Hirudinea, Piscicolidae, Piscicolinae).
AB  - Histological analysis of frontal section through the body of parasitic leeches
      (Codonobdella truncata, Caspiobdella fadejewi) of the subfamily Piscicolinae
      revealed the presence of 11 pairs of subepidermal pulsatile vesicles. The
      vesicles of C. truncata are poorly visible on the body surface, contrary to those
      of C. fadejewi, which results from the fact that in the former species the
      vesicles are located in a layer of subepidermal connective tissue thicker (82. 82
      microm) than in C. fadejewi (20.6 microm). In the studied species the pulsatile
      vesicles have a club-like shape, are surronded by a muscular tunicle and
      connected with a short canal that penetrates the body wall. Some of the sections
      show that the vesicles are divided in two chambers (lower and upper) with an
      incomplete membrane.

PMID- 16888954
TI  - [The influence of Baycox and Anticoc on the dynamics of Eimeria sp. course in
      calves].
AB  - The studies were carried out in the farm SK Bielin, on 45 calves. The prevalence
      and intensity of the Coccidia infection were determined by means of the Willis
      Schlaaf's and McMaster's methods. Whereas the Coccidia composition in the
      examined animals was determined by the morphological features of the oocysts and
      the sporulation time. The following six Eimeria species were isolated in the
      commercial farms--E. bovis, E. aubernensis, E. zurni, E. ellipsolidalis, E.
      subspherica and E. cylindrica. The calves were divided into control and two
      experimental groups--15 animals per group. Anticoc was administered for 5 days in
      a dose of 0,9 ml/ 10 kg of body weight . Baycox was administered twice in 7 days
      interval in a dose of 20 mg/kg of body weight. The weight gain and the course of
      coccidia infection in calves before and after treatment with Baycox and Anticoc
      were examined. In control group the coccidia infection was very high. After
      administration of Anticoc the intensity of coccidia infection was falling down
      and 0-180 oocysts were found in 1 g of feces. After administration of Baycox the
      intensity of coccidia infection was very low and only 0-80 oocysts were found in
      1 g of feces. The results were analysed statistically, and significant
      differences between the treated and untreated animals at P < or = 0.01 were
      observed.

PMID- 16888957
TI  - [Strongyloidosis--a case report].
AB  - A case of Strongyloides stercoralis infection was described.

PMID- 16888956
TI  - [Autoimmune thrombocytopenia in recurrent polietiological malaria (Plasmodium
      falciparum, Plasmodium vivax)].
AB  - Thrombocytopenia frequently appear in severe malaria. The reasons of low blood
      platelets count are different and its results of hypersplenism, subclinical
      course of intravascular coagulation (DIC). Thrombocytopenia from "consumption" is
      consequence of sequestration of blood platelets in blood vessels of lungs and
      cerebral. We examination 29 years old men, who was as forest worker in islands on
      Indonesia. He was treated with recurrent, poliethiological malaria (Plasmodium
      falciparum, Plasmodium vivar) and severe thrombocytopenia (17.0 G/L) without
      hepatosplenomegalia. Antiplatelet antibody was examined in blood serum by ELISA
      methods (GTI - PAKPLUS. In blood serum was detected IgG antibody agai
      nstglicoprotein receptors on surface of blood platelets GPIIb/IIIa, GPIV,
      GPIb/IX, GPV, GPIa/IIa. Chronic infections of Plasmodium may conduct to
      autoimmune destruction of blood platelets.

PMID- 16888958
TI  - [Prevelance of the etiological agent of human ehrlichiosis (HGE) in ticks from
      west-north Poland].
AB  - Ehrlichias occur in ticks in the cells of their haemolymph-hematocytes. They
      enter the vertebrate host organism with the saliva of the tick, during a blood
      meal. Humans can also be the hosts for this pathogen. Two pathogens cause a
      humane disease-monocytic ehrlichiasis (E. chaffensis) or granulocytic
      ehrlichiasis (HGE factor). The above disease units are difficult to diagnose
      because of their non-specific symptoms. A preliminary study has been conducted on
      the prevalence of the HGE factor in the ticks, Ixodes ricinus in the recreational
      areas of the West-Pomeranian Province. All forms of I. ricinus were collected
      from 3 sites. All the sites are known to be frequented by hikers and gatherers of
      forest mushrooms and berries. The site selection involved also careful
      consideration of the tree- and underbrush type. The ticks were collected twice a
      year in spring (May/June) and in autumn (August?September), which was associated
      with the biological activity of the collected acarines. A total of 1159 Ixodes
      ricinus ticks were collected, in this number 172 females, 167 males, 597 nymphs,
      and 223 larvae. Using the PCR technique, the 16SrRNA-gene fragment was amplified
      using primers specific for the HGE factor: EHR 790 and EHR 521. The studied
      population contained 3.7% infected females in spring and 2.7% in autumn, 0.68%
      infected males in spring, no infected in autumn. The nymphs were infected in
      spring (2.17%) and in autumn too (0.73%), but the larvae were not infected in
      both seasons. Analysing the above-mentioned results it can be concluded that the
      decisive majority of the individuals transmitting the HGE factor are the adult
      forms. The present study was only a preliminary one. In the future much more
      sites will be monitored, in the recreational areas of both the city of Szczecin
      and the entire province.

PMID- 16888959
TI  - [The cases of teratology in Mallophaga of South Africa].
AB  - The following types ofteratology were found in the collection of 1278 individuals
      of Mallophaga coming from the birds of South Africa origin: deformity clypeus in
      Quadraceps kilimandjarensis (KELL.) from Stephanibyx coronatus (BURCH.), partial
      atrophy of one of the antennae of two males Q. kilimandjarensis and abdomen
      plates deformity of two females Q. kilimandjarensis, in male and female
      Quadraceps chorleyi TIMM. from Hoplopterus armatus (BURCH.), in female
      Saemundssonia africana TIMM. from Stephanibyx coronatus (BODD.) and male
      Plegadiphilus threskiornis (BEDF.) from Threskiornis aethiopicus (LATH.) the only
      representative of Amblycera (the other teratology belonged to Ischnocera
      suborder). Generally teratology was found in 0.70% of the collection.

PMID- 16888960
TI  - [Taeniosis in the lower Silesia province in the 1993 - 1997 years].
AB  - This paper is the result of investigations of taeniosis in inhabitants of four
      former provinces of the Lower Silesia area in the 1993 - 1997 years. Analysis of
      frequency taneniosis (according to place of living and sex) confirmed clearly the
      decrease of tendency of thisparasitosis.

PMID- 16888961
TI  - Triungulin larvae of Meloe variegatus donov (Coleoptera: Meloidae); morphology,
      biology and an incident of apiary infestation.
AB  - The beetle Meloe variegatus is a pest of sugar beet, cabbage and winter rye. Its
      larvae are parasites and pests of solitary bees, but sometimes they get into the
      nests of the honey bee.

PMID- 16888962
TI  - Piscicola brylinskae, a new leech species from the Netherlands (Hirudinea:
      Piscicolidae).
AB  - Piscicola brylinskae n. sp. is described from the lake Vechten in the village of
      Bunnik (Prov. Utrecht), The Netherlands. The characteristic features of this
      leeches allow to conclude that this species is a member of the subfamily
      Piscicolinae, probably a parasite of fish.

PMID- 16888963
TI  - [The structure of low-abundance and crowded infrapopulations of the tapeworm
      Hymenolepis diminuta inbred line--WMS IL1].
AB  - An average of 4.9 tapeworms were discovered on day 7 of a low-abundance H.
      diminuta infection of rats of race WAG alb. After 11 months, the mean was only
      relatively slightly lower at 3.6. These means represent 97.1 and 71.4% of the 5
      cysticercoids supplied. In turn, 7 days and 11 months after rats were supplied
      with 110 cysticercoids, the respective percent-ages were 85.1 and 56.0. All 7-
      and 12-day tapeworms from the low-abundance and crowded infrapopulations were
      characterized by the presence of a terminal proglottid of lingulate shape, in
      which the excretory canals joined. In contrast, older (48-day and 11-month-old)
      worms showed typical apolysis of gravid proglottids. There were no reports of the
      destrobilation of tapeworms, and the relatively large number of tapeworms
      persisting 11 months into the infection is particularly noteworthy. The results
      point to the lack of any rapid rejection of tapeworms of the kind characterized
      in many other studies on H. diminuta.

PMID- 16888964
TI  - The effect of infestation with Diplostomum sp. on growth rate of Siberian
      sturgeon fry Acipenser baeri brandt.
AB  - The objective of the experiment was to compare the growth rate in two groups of
      Siberian sturgeon fry, one of which was infested with metacercariae of
      Diplostomum, the infestation degree was from 1 to 160/fish. The fish fed on
      natural as well as artificial food; the latter was given at the rate sufficient
      to cover 50% of the fish requirements. The average initial body weight in the
      control group was 16.8 +/- 1.9g, and in the group with Diplostomum - 28.4 +/- 3.6
      g. During the period of favorable temperatures, viz. for about 90 days, the fry
      was showed satisfactory growth, but the growth rate became inhibited as the
      temperatures decreased to below 12 degrees C, so that throughout the wintering
      period the fish weight decreased by some 10%. Fish from the control group showed
      a higher growth rate than the infested ones, and by the end of the experiment the
      controls weighted 7.5% more than the infested group in spite of their lower
      initial weight.

PMID- 16888965
TI  - [Soil contamination with Toxocara spp. eggs in the Elblag area].
AB  - The distribution of Toxocara spp. eggs in Elbl4g was studied. Out of 72 soil
      samples collected in public places of the city 13.9% were positive and the mean
      egg density was 3.75/100g soil. The city backyards were much more contaminated
      with Toxocara spp. eggs (18.0%) than the playgrounds (4.5%). In sandpits examined
      the eggs were not found. Almost 80% of Toxocara spp. eggs recovered were
      infective. T. cati eggs were more frequent than T. canis eggs. Additionally in
      examined samples two eggs of Ancylostoma caninum and one egg of Ascaris
      lumbricoides were recognized.

PMID- 16888966
TI  - [Varroa destructor (Anderson and Trueman, 2000); the change in classification
      within the genus Varroa (Oudemans, 1904)].
AB  - Varroa jacobsoni was noted for the first time in 1904, in the nest ofApis cerana.
      In Apis mellifera nests the first Varroa mites were probably found in Korea
      (1950), next in Japan (1958). In the following years they have spread all over
      the world. All the time they were regarded as V. jacobsoni. Recently Anderson and
      Trueman have proved that Varroa jacobsoni is more than one species. They gave the
      new name Varroa destructor n. sp. to the group of six haplotypes. Mites, which
      became pests ofA. mellifera worldwide, belong to V. destructor.

PMID- 16888967
TI  - [8th European Multicolloquium of Parasitology - EMOP8, Poznan 2000].

PMID- 16888968
TI  - [Professor Tadeusz Mazur (obituary notice)].

PMID- 16888969
TI  - [Molecular methods and techniques used in diagnosis and epidemiology of
      infections caused by pathogenic fungi].
AB  - In this paper we reviewed the latest literature on molecular techniques used in
      diagnosis and epidemiology of infections caused by pathogenic fungi. Traditional
      methods used for the identification and typing of medically relevant fungi
      include morphological and biochemical analysis. These methods are time-consuming
      and base on phenotypic features what makes them unreliable. We described the
      usefulness in mycological studies of fast and very sensitive molecular methods
      which rely on PCR and hybridization techniques.

PMID- 16888970
TI  - [Current data about fungi prevalence in various ontocenoses in women during
      procreation period].
AB  - The aim of study was to analyse fungi prevalence in three ontocenoses (vagina,
      oral cavity and anus) in women during procreation period, which should be helpful
      in developing prophylactic programmes for pregnant womem, newborns and infants
      infected with fungi. In 716 examined women (age 20-45 years), 1411 samples of
      appropriate biological materials were taken and inoculated in the fluid Sabouraud
      medium and then axenic fungi strains were isolated in Sabouraud agar. High fungi
      prevalence in three ontocenoses of examined women was noted. Mean percentage for
      ontocenosis was: 39% +/- 1.8% for vagina, 42.18% +/- 1.8% for oral cavity and
      25.03 +/- 1.6% for anus. These data indicate the necessity for further
      examinations of multifocal fungal infection in women during procreation period.

PMID- 16888971
TI  - [Relationship between activity of hydrolases in fungi isolated from vagina of
      pregnant women and selected symptoms].
AB  - Pregnancy is considered a factor of vulvovaginal mycosis. Secretion of hydrolases
      is an important determinant of Candida virulence. Thus, the aim of the study was
      to found the relationship between activity of 19 hydrolases in fungi isolated
      from vagina of pregnant women and symptoms of mycosis. 251 pregnant women were
      examined. Samples were collected from vagina and cultured on Sabouraud media.
      Activity of hydrolytic enzymes was evaluated using API ZYM (bioMerieux) test
      Fungi were found in 20.1% of vaginal samples. Symptoms were detected in 45.8% of
      women. Only 32.1% of women with discharge and 26.4% with pruritus had mycosis.
      Out of the 19 examined hydrolazes, 13 active enzymes were detected in fungal
      strains. We found for the first time the relationship between activity of fungal
      esterase lipase and the presence of vaginal discharge in pregnant women.

PMID- 16888972
TI  - [Analysis of sIgA concentrations in the contents of the cervical canal of the
      uterus and of the oral cavity in women with Candida or without fungi in
      ontocenoses of these organs].
AB  - The aim of the study was to search for fungi in ontocenoses of genital organs and
      oral cavity (the fungal reservoir for multifocal infections) in women; evaluation
      of the concentration of sIgA in the contents of the cervical canal of the uterus
      and of the oral cavity. 102 women (age: 18-35 years) were examined. Fungi were
      isolated from ontocenoses of the vagina and the oral cavity; axenic strains were
      differentiated with API 20 C and API 20 C AUX tests (bioMerieux). The
      concentrations of sIgA in the content of the cervical canal of the uterus and
      from the oral cavity were evaluated by LC-Partigen IgA (Behring) tests. Candida
      occurence in the oral cavity was significant (p < 0.02) higher than in the
      vagina. Candida albicans (6 codes) was the predominat species; there were also C.
      tropicalis, C. kefyr, C. krusei, C. guilliermondii and C. glabrata. There were no
      significant differences between sIgA concentrations and the presence or absence
      of fungi in the vagina or oral cavity.

PMID- 16888973
TI  - [Mycotic complications of shunt infection in children with primary
      hydrocephalus].
AB  - Recently, the incidence of fungal infections in children, including children with
      shunt-dependent hydrocephalus, has increased. The analysis comprised 8 children
      treated in the III Clinic of Pediatrics of ICZMP during the period of 12 months
      (12% of all infectious complications of the shunt system). The clinical picture
      of fungal infection included symptoms of shunt dysfunction: febrile conditions,
      vomiting, distress and loss of appetite. The most common pathogens isolated from
      the cerebro-spinal fluid were fungi from the Candida species. Mean value of
      pleocytosis in the cerebro-spinal fluid was 812 cell/microl, and mean protein
      concentration was 311 mg/dl. Treatment consisted of monotherapy with Diflucan,
      monotherapy with Ancotil or combined treatment with Ancotil and Amphotericine B.
      The drugs were administered intravenously and intraventricularly after removal of
      the shunt and application of external drainage. Sterility of cerebro-spinal fluid
      was obtained in the shortest time with the use of Ancotil. Prophylactic
      application of antifungal drugs decreases the frequency of infections in children
      with shunt-dependent hydrocephalus.

PMID- 16888974
TI  - [Occurrence of Pneumocystis carinii DNA and anti-Pneumocystis antibodies in the
      sera of infants during a period of of physiologic decreased immune response].
AB  - The polymerase chain reaction (PCR) and indirect immunofluorescent test (IF) were
      used for examination of serum samples obtained from infants with respiratory
      tract infections. Sixty (11.9%) out of the 503 examined infant samples were
      positive for anti-P. carinii IgM and 354 (70.4%) contained anti-Pneumocystis IgG.
      P. carinii DNA was found in 6 (6.7%) sera from 90 of infected infants. Five out
      these 6 samples were for anti-Pneumocystis antibodies positive; 4 contained both
      IgG and IgM classes and one had only IgG. The sixth sample had neither IgG nor
      IgM, despite of P. carinii DNA presence. The results of the studies indicated
      that for diagnosis Pneumocystis carinii pneumonia (PCP) in infants on serum
      specimens detection of antibodies by IF test is of greater value than
      Pneumocystis DNA amplification by PCR method.

PMID- 16888975
TI  - [The prevalence of Toxoplasma gondii infection among 2016 pregnant women and
      their children in the Institute of Mother and Child in Warsaw].
AB  - During the year 2000 a screening was performed to estimate the frequency of
      Toxoplasma gondii infections in 2016 pregnant women and their children in the
      Department of Gynaecology and Obstetrics and in the Outpatient Clinic of the
      Institute of Mother and Child in Warsaw. The study was based on identifying IgG
      and IgM specific antibodies. All tests were done in the Department of Immunology.
      Women with serologically diagnosed primary infection were offered further follow
      up, antibiotic therapy and care during delivery in the Institute of Mother and
      Child. Children born by infected mothers were examined serologically and observed
      in terms of congenital abnormality. There were 1294 (64.19%) seronegative; 722
      (35.81%) were infected before pregnancy (the presence of IgG antibodies). Five
      women with previous seronegative results (0.29%) were diagnosed as having primary
      infection during pregnancy. Congenital infection, confirmed serologically, was
      recognized in 3 newborn infants.

PMID- 16888976
TI  - [Detection of Toxoplasma gondii in human placenta by PCR and placental histologic
      findings].
AB  - Since isolation of Toxoplasma gondii from human placenta strongly correlates with
      fetal infection, the aims of the study were: to detect fragments of T. gondii B1
      gene in human placentae by PCR and to evaluate their pathology. 36 placentae
      included in three groups were obtained: group I (n = 7) from pregnancies with
      prenatal diagnosis of fetal toxoplasmosis; II (n = 17) from women with serologic
      features of primary infection during pregnancy; III (n and 13) from pregnancies
      with fetal T. gondii infection based on clinical signs. T. gondii DNA was found
      in 2/4 samples from the I group and in 1/14 from the II group. Villitis was
      identified in 3/15 other placentae from the II group. In the III group we did not
      recognize neither T. gondii DNA nor villitis. We consider PCR and pathologic
      evaluations of placentae as the two complementary methods. PCR can be especially
      helpful in pregnancies not screened against T. gondii as positive result in
      placenta can confirm mother's primary infection.

PMID- 16888978
TI  - Principles of contemporary treatment in trichinellosis.
AB  - Principles of trichinellosis treatment were presented, based on contemporary
      parasitologic and clinical criteria. Significance of the Trichinella sp. life
      cycle, phase of the invasion and the disease was presented. The role of
      anthelmintics was stressed, as drugs of choice in eradication of the intestinal
      phase and in prevention against development of the muscular phase. Role of
      glucocorticoids was described in suppression of acute clinical signs/symptoms.
      Pathology of the late period oftrichinellosis and of the late invasion sequele
      were discussed.

PMID- 16888977
TI  - [Detection of congenital toxoplasmosis in utero with a polymerase chain reaction
      on amniotic fluid].
AB  - To establish a prenatal diagnosis of congenital toxoplasmosis the PCR test was
      done on amniotic fluids from 47 women suspected of primary Toxoplasma infection
      during pregnancy. Fragments of Toxoplasma B1 gene were found in 5 examined
      samples. Positive tests were confirmed by mouse inoculation or by serologic
      testing of newborns. It was concluded that the PCR performed on amniotic fluid
      should be recommended for the prenatal diagnosis of congenital toxoplasmosis,
      however, negative results of the test can not rule out congenital infection.

PMID- 16888979
TI  - Clinical analysis and evaluation of selected laboratory parameters in patients
      examined in distant periods after trichinellosis.
AB  - Since early times, opinions of clinicians in distant sequele of the experienced
      once trichinellosis remain controversial. A set of studies was performed in 75
      patients who had experienced trichinellosis 1, 3, 4, 6, or 7 years earlier.
      Persistence of the general clinical symptoms and of the motor system symptoms as
      well as persistence of IgG class antibodies against the E/S antigen of
      Trichinella sp. it was found in 77.3% examined patients. In 84.0% patients
      bioelectric disturbances (EMG, ENG) were detected. Parasitological studies and
      pathomorphological examination of muscle biopsies performed in 24 patients
      pointed to degradation of Trichinella larvae and to the incompletely extinguished
      pathological process.

PMID- 16888981
TI  - Detection of Trichinella spiralis antigens in urine of men and animals.
AB  - The practical inability to diagnose Trichinella spiralis antibodies in man before
      day 20 post infection (dpi) has stimulated interest in the development of
      immunodiagnostic test to detect circulating antigens. Our previous experience
      showed that soon after infection immune complexes as well as uncomplexed parasite
      antigens in sera of infected rats could be detected. To diagnose the presence of
      antigen in urine, double sandwich-capture ELISA was applied using a peroxidase
      conjugated rabbit immunoglobulin to T. spiralis larval antigens. The plates were
      coated with metabolic (AES) or somatic (AS) larval antigens. Mice were infected
      with 500 T. spiralis larvae. The urine samples from experimentally infected mice
      taken from 1 to 41 dpi. and the urine samples from patients of the Clinical
      Hospital in Bialystok taken from 3 to 120 dpi were examined. Before testing, the
      urine samples were heated for 6 min. at 100 degrees C and centrifuged for 6 min.
      at 5000 g, supernatants were used in ELISA. The presence of T. spiralis antigens
      in mice urine samples was detected between 6-26 days post infection (dpi) using
      double sandwich-capture ELISA. All samples taken later were negative as samples
      taken from uninfected mice. 3 from 9 human urine samples taken 3-10 dpi were
      positive, the remaining samples taken 3-10 and 10-30 dpi showed values near to
      "cut-off". In both mice and human urine samples the higher level of antigens was
      detected in ELISA when somatic larval antigen was used. The T. spiralis antigens
      were present in urine of infected men and mice in the first phase of infection.

PMID- 16888980
TI  - Attempts of modification of apoptosis in the course of experimental
      trichinellosis in mice.
AB  - The influence of the some immunomodulators (PHA-P, TFX and dexamethasone) on the
      process of apoptosis, occurring in the course of trichinellosis in mice, has been
      studied. It has been found that PHA-P activates this process in the jejunum
      mucosa and prolongs it in the muscular inflammatory infiltration, whereas TFX has
      no influence and dexamethasone distinctly decreases the level of the apoptotic
      cells. The number of the intestinal trichinae on the successive days of infection
      was similar in all groups of animals, however, the number of the muscular larvae
      in the groups receiving immunostimulators was much lower and in the group treated
      with dexamethasone--a little higher than that in control. As in mice receiving
      PHA-P and TFX, the cellular inflammatory infiltration in the muscles was larger
      than that in control, and in the group to which dexamethasone was administrated-
      smaller, the authors think that it was extensiveness of the infiltration and not
      the level of the apoptotic cells that influenced the number of the outliving
      larvae.

PMID- 16888982
TI  - Glutathione-S-transferase activity in mouse muscle during experimental
      trichinellosis.
AB  - The role of glutathione-S-transferase (GST, EC 2.5.1.18) in biochemical host
      defence in experimental trichinellosis was evaluated. The activity of GST in
      mouse skeletal muscles was measured during the muscular phase of trichinellosis,
      starting from the 3rd week post infection (w.p.i.) to the 11th w.p.i. Activity
      was determined spectrophotometrically by monitoring the formation of thioether (S
      2,4-dinitrophenylglutathione) from the reduced form of glutathione and 1-chloro
      2,4-dinitrobenzene used as a substrate and as an example of xenobiotics. The
      changes in the activity of GST were as follows: an increase in activity starts in
      the 4th w.p.i., peaks (up to 310% of the normal value) in the 6th w.p.i.,
      decreases in the 8th week and a final, weak rise was observed in week 11. The
      statistically significant changes in GST activity in this phase of experimental
      trichinellosis suggest that this enzyme participates in the biochemical defence
      of the host against Trichinella infection.

PMID- 16888983
TI  - Trichinellosis in swine and wild boars in Poland from 1993 to 1998.
AB  - The prevalence of Trichinella sp. among 97, 193, 480 swine and 309,040 wild boars
      was determined by artificial digestion method. Pork meat was about 6 times less
      infected with Trichinella sp. in the years 1997-1998 than in the years 1993-1994.
      In the years 1993-1994 894 positive Trichinella sp. cases (prevalence--0.0029%)
      in pork meat were established. The prevalence of Trichinella larvae infection in
      pork meat in the years 1997-1998 was 0.00030%--larvae were found in 141 cases,
      only.

PMID- 16888984
TI  - Trichinellosis in Poland during recent years (1996-1999).

PMID- 16888985
TI  - [Introduction to biology and control of mosquitoes].
AB  - Mosquitoes systematics, life cycle as well as morphology and bionomics of
      developmental stages, mosquitoes borne diseases, ecology and reemergence,
      vectorial capacity of some domestic species were presented with regard to
      mosquitoes control by the integrated methods and ecological prophylaxis.

PMID- 16888986
TI  - [Biology of house dust mites (Acari: Astigmata: Pyroglyphidae)].
AB  - This article is a first part of the rewiev of the house-dust-mite-atopy problem
      data. It includes informations on biology of these mites with emphasis of medical
      aspect and control. We hope that these informations will be of considerable
      interest to many readers because of the greatly increased investigations into the
      role of house dust mite sensitivity in allergic diseases.

PMID- 16888987
TI  - [House dust mites (Acari: Pyroglyphidae) as the frequent cause of allergies in
      humans].
AB  - House dust mites from the family Pyroglyphidae (Dermatophagoides pteronyssinus,
      D. farinae and Euroglyphus maynei) are recognized as the major source of
      allergens in house dust and indoor environment. In this review their
      allergenicity, diagnostics and some biochemical and allergological assays of the
      allergens produced by these mites are discussed. A brief summary of the mite
      derived allergens, their occurrence in some indoor environments and annual
      dynamics of the mite populations are provided as background.

PMID- 16888988
TI  - [Antigens of Toxoplasma gondii].
AB  - The paper presents antigenic structure of T. gondii tachyzoites and bradyzoites
      in respect of potential use of some chosen antigens for diagnostic and
      immunoprophylactic purposes.

PMID- 16888989
TI  - Compatibility in snail--fluke associations.
AB  - The compatibility of the species forming the fluke-snail complex is biochemical
      in nature. Trematode larvae are capable of modulating the immunological response
      of the host, while snails are capable of secreting substances affecting the
      mobility of the parasites invasive stages.

PMID- 16888990
TI  - [Attempt of deworming of red and fallow deer in deer farm with rintal premix].
AB  - Rintal 2.4% premix (Bayer) in single dose 7.5 mg of active substance on kg body
      weight was given to the calves of red and fallow deer. Effectiveness of deworming
      against nematodes from family Trichostrongylidae was 85.2% in red and 97.8% in
      fallow deer. Against namatodes from genus Trichocephalus the effectiveness was
      higher extending in red deer 98.1%, and in fallow deer 99.5%. Anthelmintic was
      not effective against nematodes Varestrongylus sagittatus and Elaphostrongylus
      cervi.

PMID- 16888991
TI  - Parasites of Chaffinch (Fringilla coelebs) population. Part I. Coccidia
      (Protozoa, Apicomplexa).
AB  - Coccidia infection in Chaffinch population in Mazurian Lakeland was studied.
      Birds were caught in mist nets from June to September and droppings were
      collected after defecation. Prevalence of infection was high -80% of Chaffinches
      excreted oocysts of Isospora sp. Intensity of oocysts' production varied
      depending on the time of the day and therefore coccidia prevalence in Chaffinch
      should be best detectable in birds caught after midday.

PMID- 16888992
TI  - Where have all the fleas gone? Low levels of Blue Tit Parus caeruleus nests
      infestation.
AB  - Prevalence of flea infestation in nests of Blue Tit Parus caeruleus was analyzed
      and compared with these of other hole-nesting birds. Nests were collected from
      nestboxes prior to youngs fledging. It was found that prevalence of fleas was
      very low in comparison to other studies of Blue Tits nests and to other bird
      species. The possible reasons of this low prevalence are discussed.

PMID- 16888993
TI  - [The occurrence of Ixodes ricinus in the select recreative areas in the Province
      of Szczecin. Part I].
AB  - Among Polish ticks species the most common Ixodes ricinus has the biggest medical
      importance. Within the last few years, the incidence of disease transmitted by
      ticks has rapidly increased. We have made a thorough analysis of the quantative
      and rate per cent of occurrence of various stages Ixodes ricinus in the forest
      areas of some places in Szczecin province and in the parks of Szczecin, that are
      known as highly recreative and frequently visted by many people. A total of 426
      (68% numphs) specimens collected there show that ticks frequently occupy habitats
      closely associated with man.

PMID- 16888994
TI  - [Biography of Professor Jan Starzyk, Ph.D].

PMID- 16888995
TI  - [Scientific conference: "Biology and Ecology of Vectors in Fighting Diseases"].

PMID- 16888996
TI  - Occurrence of the spirochetes Borrelia burgdorferi Sensulato in ticks Ixodes
      ricinus (L.) from selected municipal woods of the city of Poznan.

PMID- 16888997
TI  - Vectors of lymphatic filariasis of human.

PMID- 16888998
TI  - Integrated methods of mosquito control in Wroclaw area.

PMID- 16888999
TI  - Seasonal and diurnal activity of ticks Ixodes ricinus (Linnaeus, 1758) in Masyw
      Sleza (lower Silesia).

PMID- 16889000
TI  - Phytoparasitic nematodes of forest ecosystems of the Ukrainian Carpathians.

PMID- 16889001
TI  - Phytoparasitic nematodes of Pinus mugo turra in the highlands of the Ukrainian
      Carpatihans.

PMID- 16889002
TI  - Basic research to uncover stimuli for environmentally sound control of house
      flies.

PMID- 16889004
TI  - Biology of vectors of cestodes in Antarctic.

PMID- 16889003
TI  - Role of gastropods in epidemiology of human parasitic diseases.

PMID- 16889005
TI  - Ecology of ectoparasite vectors.

PMID- 16889006
TI  - Effect of temperature and relative humidity on the development and hatching of
      larvae of the tick Dermacentor reticulatus (Fabricius, 1794) (Acari: Ixodida).

PMID- 16889007
TI  - Epidemic threat caused by mosquitoes (Culicidae).

PMID- 16889009
TI  - Ecological differences amoung four genera of Phthiraptera infesting south-eastern
      Brazilian humming-birds.

PMID- 16889008
TI  - The need of schooling in environmental-aware methods of mosquito control.

PMID- 16889010
TI  - Physiological control of host-seeking behavior by mosquitoes.

PMID- 16889011
TI  - Laboratory vector models in regard to animal protection legislation.

PMID- 16889012
TI  - [Toxoplasma gondii proteome].
AB  - The article presents data concerning methods of proteomics and main achievements
      of studies on Toxoplasma gondii proteom.

PMID- 16889013
TI  - [Transgenic bioinsecticides inimical to parasites, but imical to environment].
AB  - Identification of Bacillus thuringiensis (Bt) parasporal crystalline inclusions
      composed of Cry proteins (=delta-endotoxins) resulted in introduction of
      microbial pesticides for biological control of some parasites. Delta-endotoxins
      are encoded by cry genes and are active against pest and nuisance insects (mostly
      mosquitoes and black flies--vectors of still important infectious diseases). The
      recent significant progress in DNA recombination technique may overcome
      limitations (a short residual persistence and a narrow spectrum of activity)
      associated with application of Bt conventional products. An introduction of cry
      genes from mosquitocidal subspecies B. th. israelensis (Bti) to the aquatic
      microorganisms inhabiting the same water bodies as mosquito and fly larvae
      (Diptera), has considerably improved the toxin delivery system to target insects.
      However, in the first experiments, in which Bti genes were cloned in
      cyanobacteria (Agmenellum quadruplicatum, Synechocystis PCC6803), a low gene
      expression was observed. Thus, it was necessary to integrate cry genes with
      strong promoters or to increase the number of vector-introduced copies. To
      overcome the obstacles of low gene expression and regulatory restriction for
      recombinant organisms, Bti spore/crystal formulations were encapsulated in the
      aquatic protozoan, Tetrahymena pyriformis. Large numbers of crystals (180 to
      240/cell) were accumulated in its food vacuoles. This system resulted also in an
      increase in toxin persistence from 24 to 71 h. Cloning Bti genes in B. sphaericus
      (which also produces mosquitocidal proteins) was another way of an increasing Bt
      crystal residual activity. In this case, the crystals were additionally protected
      by B. sphaericus exosporium. These transgenic bacteria produced large amounts of
      delta-endotoxins that remained under water surface longer than the wild B.
      sphaericus strains. Moreover, they had a broader spectrum of insecticidal
      activity, because B. sphaericus is toxic mostly to Culex and Anopheles, and Bti-
      mostly to Culex, Aedes and some Simmulidae. Gram-negative bacteria (Asticcacaulis
      excentricus, Caulobacter crescentus and Ancylobacter aquaticus) turned out also
      to be effective delta-endotoxin producers. They grow on simple media and do not
      contain proteases which could degrade Cry proteins. In some cases, 100% mosquito
      larvae mortality was observed as a result of an exposure to transgenic
      microorganisms containing Bti genes. However, transgenic techniques are still not
      very popular in the world, despite their efficacy in biological control of
      insects. The transgenic organism construction is expensive and time-consuming.
      Genetic engineering is still raising a lot of anxieties and doubts concerning
      inappropriate use of modified organisms. On the other hand, this technology could
      solve many problems associated with vectors of important diseases, which are
      still unapproachable to contemporary medicine.

PMID- 16889014
TI  - [Occurrence of parasitic Metazoa of bream (Abramis brama) in the natural and
      artificial reservoirs in Poland].
AB  - The occurrence of parasitic Metazoa of bream in Poland was analyzed. Three types
      of reservoirs were studied--lakes, lakes heated with thermal effluents and
      artificial reservoirs. The estimated model S = 3.367 * ln(N)--1.192 described
      relationship between sample size and richness of the component community of bream
      parasites in lakes. On the basis of this model the confidence intervals for each
      artificial reservoir and thermally affected lake were computed. The richness of
      the component communitites of bream did not depend on the type of reservoir
      (natural vs. artificial). It was affected by the thermal effluents (richer
      communities in heated lakes), geographical isolation of the reservoir, and young
      age of the reservoir. Most spectacular influence of the artificial origin of the
      reservoir was found in Monogenea (group missing in 5-year old reservoir) and
      Acanthocephalus anguillae (present in 1 out of 4 artificial reservoirs).

PMID- 16889015
TI  - Parasites of chaffinch (Fringilla coelebs) population. Part II. Blood parasites.
AB  - Blood parasites of Chaffinches caught from June to October near Luknajno Lake
      (Mazurian Lakeland) were studied. Only parasites belonging to the genera
      Haemoproteus were found. A decrease in prevalence as the season progressed was
      observed. No differences in blood parasite infections in relation to the sex of
      the birds were found. Also males body weight was not affected by the presence of
      parasites.

PMID- 16889016
TI  - [Prevalence of Borrelia burgdorferi sensu lato in ticks, Ixodes ricinus in
      Tarnowskie Gory district].
AB  - Borrelia burgdorferi is an aetiological factor of borreliosis (Lyme disease). The
      main vectors of Borrelia burgdorferi are larvae, nymphs, and females of Ixodes
      ricinus. The aim of this paper was to analyse infection parameters of Borrelia
      burgdorferi in a selected populations of Ixodes ricinus. The study was conducted
      in Tarnowskie Gory administrative district (Krupski Mlyn, Zielona, Lubliniec,
      Tarnowskie Gory, Swierklaniec, Tworog, and Zbroslawice). A total of 85 ticks were
      collected with a piece of cloth dragged over the vegetation. The Borrelia
      burgdorferi infection was confirmed with a PCR method, using flagellin protein
      gene DNA amplification. DNA of Borrelia burgderferi sensu lato was present in 14
      ticks, which constituted 16.5% of the population studied. The percentage of
      infected females and nymphs was 26.8%, 22.2%, and 5.6%, respectively. A high
      prevalence of the pathogen (50%) was in ticks revealed in the recreation areas
      and the community forest in Swierklaniec.

PMID- 16889017
TI  - [The prevalence of anti-Toxoplasma gondii antibodies among abattoir workers in
      Lublin].
AB  - Abattoir workers are occupationally exposed to Toxoplasma gondii by the contact
      with raw meat. One hundred and seven abattoir workers from the Meat Factory in
      Lublin were examined for the presence of anti-Toxoplasma antibodies. Sixty-one
      blood donors were also tested as the reference group. Sera from workers and
      referents were tested by direct agglutination with 2-mercaptoethanol (DA-2ME),
      and also by ELFA IgG and ELFA IgM tests (Vidas Toxo IgM, Vidas Toxo IgG,
      bioMerieux, France). In the workers group, out of 107 tested sera, 70 were found
      positive (65.4%). The highest percentage of seropositive results was found in the
      Cured Meat Division--76.2%. In the Meat Production Division 66.6% of seropositive
      results were found, and in the Slaughter Division--46.1%. Three persons with the
      presence of IgM antibodies were found in the Cured Meat Division. In the
      reference group, 34 out of 61 sera (55.7%) were positive. The difference in
      seropositivity between Cured Meat Division workers and reference group was
      statistically significant (p < 0.05). The high percentage of seropositive
      reactions among the workers of Cured Meat Division and the presence of persons in
      early stage of invasion suggest an increased risk of exposure to T. gondii in
      this section.

PMID- 16889018
TI  - [Soil contamination with Toxocara spp. eggs in the Katowice area and its
      environs].
AB  - Toxocara spp. is a nematode which causes "larvae migrans visceralis" syndrome in
      human, especially in children. Cats and dogs are the source of infective eggs of
      this parasite in human environment. The eggs appear in a soil of urban and rural
      areas in large number. We have investigated samples of a soil from the recreation
      areas in Katowice city and its suburbs. The goal of this study was to determine
      the degree of soil contamination with eggs of Toxocara spp. Of 157 samples
      examined 79 (50%) contained the eggs. The highest number of eggs has been found
      in samples collected from landscapes, particulary from the lawn and playgrounds.

PMID- 16889019
TI  - Effect of electromagnetic waves on sensitivity of fungi of the genus Candida to
      miconazole.
AB  - Increasing use of elctromagnetic fields (EF) in the treatment of various diseases
      may have potential impacts on fungi--possible aetiological factors of concomitant
      mycoses. The aim of this study was to investigate the effects of EF on miconazole
      susceptibility among fungi of the genus Candida showing confirmed pathogenicity
      in humans. Fifteen Candida strains obtained from patients were used and their
      susceptibility to miconazole was determined by diffusion in agar gel. Antifungal
      activity of miconazole was assessed as minimal inhibitory concentration (MIC)
      which was calculated for Candida strains not exposed to EF (control) and EF
      exposed (3 experiments). In the majority of cases the susceptibility of Candida
      species to miconazole decreased (higher MICs) after the first week of EF
      exposure, regardless of the EF's parameters. This was followed by an increase in
      susceptibility (lower MICs) after the second week of exposure to EF of 2 mT
      intensity and frequency 3 Hz (experiment I) and an EF of 9 mT intensity and 12.5
      Hz frequency (experiment II) relative to control. An increase in susceptibility
      (lower MICs) was observed in the second week of exposure, whatever the parameters
      of the EF. The application of low intensity, low frequency EF for a period of at
      least two weeks may be beneficial in the treatment of mycoses caused by
      pathogenic fungi of Candida genus.

PMID- 16889020
TI  - [Prof. Alicia Kurnatowska: 50 year jubilee of her scientific work in the field of
      parasitology and medical mycology].

PMID- 16889021
TI  - [Calodium hepaticum (Bancroft, 1893) Moravec, 1982--capillaria with an atypical
      life cycle].
AB  - Calodium hepaticum (Bancroft, 1893)--commonly known as Capillaria hepatica is a
      nematode parasitising in liver of rodents, some domestic and wild mammals:
      Insectivora, Carnivora, Artiodactyla and Primates including human as well. C.
      hepaticum is the only nematode--geohelminth, which for the continuity of the life
      cycle needs the death of the host being the intermediate and final host at the
      same time. The eggs of the parasite deposited by female worms in liver of the
      host became entrapped in fibrotic tissue. C. hepaticum is a cosmopolitic
      nematode. Rats and mice (domestic and field) are the main hosts of this parasite,
      the prevalence of infection can be very high e.g. Rattus norvegicus--100% in the
      Baltimore Zoo (Farhang-Azad 1977) as well as from the urban area of Milan (Italy)
      -the prevalence of infection was 36% (Ceruti et al. 2001). Hepatic capillariasis
      was not recorded in our country but its existence seems to be very probable.

PMID- 16889022
TI  - Diversity of the parasite fauna of cyprinid (Cyprinidae) and percid (Percidae)
      fishes in the Vistula Lagoon, Poland.
AB  - A total of 2398 fish specimens (1091 Percidae and 1307 Cyprinidae) belonging to
      16 species (3 Percidae and 13 Cyprinidae), caught in the Polish part of the
      Vistula Lagoon were examined within December 1994-March 1997. The parasites found
      were identified as belonging to 63 taxa (61 species as well as Diplostomum spp.
      flukes and glochidia Unionidae gen. sp. which could not be identified to species)
      of the Microsporea (1), Protozoa (1), Myxozoa (2), Monogenea (10), Digenea (15),
      Cestoda (11), Nematoda (11), Acanthocephala (5), Hirudinea (1), Mollusca (1),
      Copepoda (4), and Branchiura (1). The percids and cyprinids were found to support
      37 and 40 parasitic taxa, respectively, the taxon-richest parasite fauna
      occurring in zander, Sander lucioperca (26 taxa), followed by carp bream, Abramis
      brama (24), European perch, Perca fluviatilis (24), roach, Rutilus rutilus (19),
      ruffe, Gymnocephalus cernuus (15), and Prussian carp, Carassius gibelio (11). The
      remaining fish species hosted less than 10 parasitic species each. Metacercariae
      of the genus Diplostomumn, found in about 37% of the fish examined, and
      Tylodelphys clavata, recorded in about 24% of the fish, proved the commonest
      parasites. The study showed the Vistula Lagoon cyprinid and percid parasite fauna
      to be dominated by freshwater species, frequencies of their occurrence in the
      brackishwater lagoon being lower than those in freshwater reservoirs. Frequencies
      of the 6 marine parasitic species found in the lagoon were, too, lower than those
      in the sea. It is suggested that some of the parasites (Ancyrocephalus paradoxus,
      Diplozoon paradoxum of the Monogenea, Diplostomum spp., Tylodelphys clavata of
      the Digenea, and Achtheres percarum of the Copepoda) prefer brackishwater
      habitats.

PMID- 16889023
TI  - [Evaluation of occurrence of spirochetes Borrelia burgdorferi sensu lato in
      Ixodes ricinus ticks in selected areas of the Lublin region by polymerase chain
      reaction method (PCR)].
AB  - During the period 2001-2002, 1098 Ixodes ricinus ticks were collected at forest
      sampling sites and the degree of their infection with Borrelia burgdorferi
      spirochetes was determined by means of polimerase chain reaction (PCR). The
      presence of Borrelia burgdorferi genetic material was noted in 69 cases (6.3%).
      It was confirmed that the frequency of infection of adult forms of ticks (males
      and females) was nearly twice as high as nymphs. The highest degree of infection
      was observed in females--9.5%. The degree of infection among males and nymphs was
      smaller--5.9% and 4.4% respectively in individual provinces. The percentage of
      infected females ranged from 7.9% in the Zamosc Province to 13.6% in the Wlodawa
      Province. In males, the percentage of infected ticks remained within the range
      from 3.1% in the Lublin Province to 13.3% in the Lubartow Province.

PMID- 16889024
TI  - Prevalence of potentially pathogenic fungi in the bathing sites of the Sulejow
      Reservoir.
AB  - Progressive degradation of water ecosystems may contribute to the propagation of
      fungi pathogenic to humans and animals. The aim of this study was a quantitative
      evaluation and identification of species of potentially pathogenic fungi in the
      littoral zone of the Sulejow Reservoir used as recreation site. We studied
      samples of surface water and sediments collected from 6 sampling sites of the
      reservoir in the years 2000 and 2001. In 2000, fungi were isolated from 82.7% of
      samples, while in 2001 from as many as 95.4%. There were 28 species representing
      genera: Candida, Cryptococcus, Geotrichum, Kloeckera, Rhodotorula, Saccharomyces,
      and Trichosporon. The most common species were Rhodotorula glutinis and Candida
      guilliermondii. The density of the population of identified species depended on
      the season and sampling site and ranged from 80 to 328000 cells/dm3 (also
      uncountable growth). The waters of the Sulejow Reservoir may be a covenient place
      of anamorphic developmental forms, for the 15 cultured species which can also
      propagate in humans and other mammals.

PMID- 16889025
TI  - Preliminary evaluation of maternotoxic effect of Ascaris extract in mice.
AB  - Administration intraperitoneally of the Ascaris suum extract--ASE-(0.6-1.4 g of
      Ascaris proteins/kg/day) at a late stage of organogenesis (8-12 days of
      gestation) disturbed course of mouse pregnancy. It has been found that injections
      of higher doses of ASE to pregnant mice caused the symptoms manifesting maternal
      toxicity (decreased body weight gain/p < 0.001/as compared to control,
      intrauterine resorption of litter, vaginal hemorrhages, female mortality and
      altered behaviour). There is a linear interrelationship between the logarithm of
      the dose of ASE and mortality of pregnant mice. The DL50 value of Ascaris
      proteins for pregnant mice was 1.02 g/kg/day (confidence interval 0.97-1.07
      g/kg/day). ASE exerted embryotoxic effects: significantly decreased the number of
      surviving fetuses per litter and the mean body weight of fetuses, increased the
      number of fetal resorptions.

PMID- 16889026
TI  - The study of cell and tissue mechanisms of the homeostasis of "helminth-host"
      system at muscle trichinellosis before and after the administration of a herb
      biostimulator and anthelminthic.
AB  - Results of micromorphological and histological studies of larvae of Trichinella
      spiralis and T. pseudospiralis, as well as, muscles, liver and small intestine of
      the rat-host before and after biostimulator administration of phytohemagglutinin
      and phytoanthelminthic were presented. It has been established that rats with
      Trichinella larvae of both species developed unspecific allergic angiomyositis,
      hepatitis, cholangitis, and erosio-haemorrhagic enterocolitis in the host's
      organism on the 35th day after infection. Furthermore, processes of compensatory
      hypertrophy, that support the host's (rats) homeostasis, on cell and tissue
      levels, were observed at histodestructional and morpho functional deficiency. It
      has been revealed that phytohemagglutinin, biostimulator injected into the host's
      organism before infection, is of immunostimulating nature and partially destroys
      the larvae of Trichinella. The phytoanthelminthic produces a significant
      trichinellocide effect: RNA synthesis and glycogen is intensified in the organs
      of the treated animals, their pathomicromorphogenesis weakened, and their
      compensatory and regenerative processes were observed. The combined use of the
      phytohemagglutinin and phytoanthelminthic fails to intensify the mentioned
      effect.

PMID- 16889027
TI  - [The influence of levamisol on the level of total protein in haemolymph of bees
      infected with Varroa destructor].
AB  - The studies were performed in 1997 in bee colonies with carnica queens. Levamisol
      in dose 2,5 mg/l and 5 mg/l of sugar syrup was given to experimental group, while
      the control one was treated with the same dose of sugar syrup. From May to
      September, once a month, the segments of honeycombs containing 15-17 day brood
      were taken for farer housing. The level of total protein was investigated in the
      haemolymph of freshly hatched bee workers. It was found that levamisol given in
      sugar syrup did not caurse disturbances in the development of bee colonies,
      however, it was noticed that levamisol influenced on the rise of total protein
      level in haemolymph of bees and decrease of Varroa destructor infection.

PMID- 16889028
TI  - [The chaos theory in parasitology].
AB  - Fundamental ideas of the chaotic non-linear dynamical systems and their
      application in parasitology (e.g. Cephalomyvia populations, Trichomronas
      vaginalis invasions, Homo-Plasmodium systems) are discussed.

PMID- 16889029
TI  - [Eosynophils in parasitic infections--clinical and functional significance].
AB  - Eosinophils are multifunctional cells which contain and produce many biologically
      active substances. Their presence is mainly associated with parasitic infections
      or allergic manifestations. Eosinophilia is a common feature of helminth
      infections occurring both in the blood and at local sites of infection. The
      highly toxic basic proteins in eosinophil granules exert a range of biological
      effects not only against helminth parasites but also in host tissue being
      responsible for their damage. Eosinophils have been shown to be strong effectors
      killing helminth parasites in vitro, especially the larval stages. However, this
      function in vivo was established only for the very small number of parasites. In
      the last years an opportunity has appeared to perform experiments with parasites
      on genetically modified mice: over expressing the gene encoding Il-5 as well as
      lacking some receptors on eosinophils. These new studies in mice demonstrated
      that Il-5 and eosinophils had a different impact on different helminth
      infections. Eosinophilia in human patients has only a limited predictive value
      for the presence of helminth infections. However, the likelihood of the presence
      of helminth infections increases considerably with the extent of eosinophilia.

PMID- 16889030
TI  - [Prevalence of Borrelia burgdorferi sensu lato in Ixodes ricinus population in
      forests of north-western Poland].
AB  - The ticks Ixodes ricinus were collected during three growing seasons in forested
      areas of north-western Poland. The ticks were collected by flagging at 30 sites.
      The specimens collected (nymphs and adults) were subjected, after an appropiate
      treatment, to indirect immunofluorescence analysis (IFA). In addition, effects of
      temperature and atmospheric precipitation on the tick infection with the
      spirochaete Borrelia burgdorferi were investigated based on data supplied by the
      Institute of Meteorology. A total of 8519 individuals of I. ricinus were
      collected at the sampling sites within May-October of three consecutive years.
      The pool of individuals obtained consisted of 7356 nymphs, 559 females, and 604
      males. The B. burgdorferri prevalence varied rather widely, from 10 to 19%.
      Compared to nymphs, adult individuals showed a higher infection rate. A
      relationship between infection rate and I. ricinus activity in different years
      and months was studied in detail. The boreliosis risk was found to increase with
      increasing tick activity. On the other hand, no correlation was found between the
      meteorological parameters (temperature, precipitation), tick abundance, and the
      B. burgdorferi infection rate.

PMID- 16889031
TI  - [Occurrence of Babesia microti in ticks Ixodes ricinus on selected areas of
      western Pomerania].
AB  - The aim of present study was to evaluate acquisition risk of babesiosis in human
      population exposed to ticks Ixodes ricinus by examination of Babesia microti DNA
      occurrence in ticks of all development stages. The polymerase chain reaction
      (PCR) was applied to estimate the occurrence of DNA Babesia microti in Ixodes
      ricinus. The Bab1 and Bab4 primers were used to amplify fragment. 238bp in
      length, of 18S rRNA gene for small ribosomal subunit. Amplicons were
      electroforeticaly separated in agarose gels. Ticks were collected in year 1999
      and 2000, twice in each year in spring-summer (May-July) and summer-autumn
      (August-October) seasons from Goleni6w Forest and Pobierowo. These places have
      been classified as people attendance and tourist areas. The 716 I. ricinus ticks
      were collected in 1999 with 61.3% of nymphs, 17.8% larvae, 10.9% females and 9.9%
      males. Highest range of infection was observed in females--28.8% studied, than
      males--18.3%, nymphs--7.7% and larvae--3.l1%. The total number of 416 I. ricinus
      was collected in year 2000 with 64% of nymphs. 13.4%/males. 11.9% females and
      10.7% larvae. The infection with Babesia microtri occurred only in three nymphs,
      which was 0.7% of studied population.

PMID- 16889032
TI  - [Occurrence and morphology of some predatory fungi, amoebicidal, rotifericidal
      and nematodicidal, in the surface waters of Bialystok region].
AB  - Studies concerned the occurrence of some predatory fungi in the surface waters:
      springs, rivers, lakes and ponds of Bialystok region, collected in years 1999
      2002. The following species of predatory fungi, amoebicidal, rotifericidal and
      nematodicidal were found: Arthrobotrys oligospora Fresenius, Zoophagus insidians
      Somlnestorff, Somnuerstorffia spinosa Arnaudov, Dactylaria brochopaga Drechsler,
      Euryancale sacciospora Dreschler and Zoopage phanera Drechsler. Physico-chemical
      parameters of waters in basins and water-courses did not prove important effect
      on existence of fungi. A little more species of predatory fungi were recorded in
      samples of water in early spring and late autumn.

PMID- 16889033
TI  - Digenean fauna of the great cormorant Phalacrocorax carbo sinensis (Blumenbach,
      1798) in the brackish waters of the Vistula Lagoon and the Gulf of Gdansk
      (Poland).
AB  - The great cormorant Phalacrocorax carbo sinensis (Blumenbach, 1798) is one of the
      most important birds in the Vistula Lagoon and the Gulf of Gdansk area. As a
      typical piscivore, the bird plays a significant part in life cycles of parasites
      in aquatic ecosystems. Within January 2000-June 2001, a complete helminthological
      examination was performed on great cormorants collected in the nesting area at
      Katy Rybackie on the Vistula Spit (80 specimens) and in the Vistula Lagoon (10
      specimens). The infection prevalence, mean intensity, and intensity range were
      92.2%, 376.5, and 1-4524, respectively. The presence of 9 digenean species
      (Paryphostomum radiatum (Dujardin, 1845), Petasiger exaeretus Dietz, 1909, P.
      phalacrocoracis (Yamaguti, 1939), Mesorchis pseudoechinatus (Olsson, 1876),
      Metorchis xanthosomus (Creplin, 1846), Cryptocotyle concavum (Creplin, 1825),
      Hysteromorpha triloba (Rudolphi, 1819), Tylodelphys clavata (Nordmann, 1832), and
      Holostephanus dubinini Vojtek et Vojtkova, 1968) was recorded, P. phalacrocoracis
      being the most common parasite (prevalence 92.2%, mean intensity 323.8).
      Tylodelplhys clavata proved a parasite new for the great cormorant moreover the
      records of P. phalacrocoracis, H. triloba, and H. dubinini are the first in
      Poland, while C. concavum and M. pseudoechinatus were for the first time recorded
      in the great cormorant in Poland.

PMID- 16889034
TI  - [Helminths of wolves (Canis lupus) from south Mazurian Lakeland, a coprological
      study].
AB  - 52 wolf scats collected during winter 2001/2002 in Puszcza Piska and Napiwodzko
      Ramuckic forests were examined using Fulleborn's method. The overall helminth
      prevalence was 28.8%. Six helminth species were recorded, the most frequent
      species were Uncinaria stenocepmhala/Ancylostoma caninmu (treated together; found
      in 6 samples), Toxocara canis and Trichuris vulpis (both identified in 4
      samples). The mean intensity of egg expulsion was 2.0 eggs/g feces, the most
      intense infection was this with Toxocara canis (average 23.0 eggs/g feces). There
      were observed differences in prevalence of parasite' species between packs.
      Present paper is first such an investigation in northeastern Poland.

PMID- 16889035
TI  - [Helminths of dogs and the soil contamination in Warsaw area].

PMID- 16889036
TI  - [The role of hemocytes in the defensive reactions in insect].

PMID- 16889037
TI  - [Analysis of philogenetic relations among six species of Diplostomum].

PMID- 16889038
TI  - [Second Thematic Validation Workshop--Parasite Fauna, Wilno, Lithuania].

PMID- 16889039
TI  - [The activity of prof. dr hab. med Jozef Grott at the field of clinical
      parasitology].

PMID- 16889040
TI  - [About use of some parasitological termsin writing].

PMID- 16889041
TI  - [A "problem" patient in nephrology].

PMID- 16889042
TI  - [Urine excretion of a monocytic chemotaxic protein-1 and a transforming growth
      factor beta1 as an indicator of chronic glomerulonephritis progression].
AB  - AIM: To measure urine and renal tissue levels of profibrogenic mediators
      (monocytic chemotaxic protein-1-MCP-1 and transforming growth factor beta1 - TGF
      b1) in patients with chronic glomerulonephritis (CGN); to specify significance of
      these mediators for assessment of inflammation and fibrosis in the kidney and as
      prognosis criteria. ELISA, immunohistochemical tests, morphometry were used to
      study urine excretion of MCP-1 and TGF-b1, expression of TGF-b1 in renal tissue,
      interstitial area, respectively, in 63 patients with active proteinuric CGN.
      RESULTS: Patients with active proteinuric forms of CGN have higher urine
      excretion of MCP-1 and TGF-b1 than healthy controls. Urine excretion of MCP-1 in
      patients with nephrotic syndrome was significantly higher than in patients with
      moderate urinary syndrome. The highest MCP-1 urine excretion was observed in
      patients with persistent renal failure. Urine excretion of TGF-b1 depended on the
      level of creatinemia being the highest in marked proteinuria and stable renal
      dysfunction. Intensive urine excretion of TGF-b1 occurred in CGN patients with
      expression of this cytokine in renal interstitium. This confirms its local-renal
      origin. A correlation was found between urine values of MCP-1, TGF-b1 and
      severity of tubulo-interstitial fibrosis (TIF). High informative value
      (sensitivity and specificity) of urine MCP-1 and TGF-b1 are for the first time
      shown as markers of interstitial fibrosis. They are also important for making
      prognosis of CGN. CONCLUSION: It is shown that MCP-1 and TGF-b1 are essential for
      remodeling of tubulointerstitium. The urinary parameters mark TIF and can be used
      as criteria of activity and prognosis of CGN.

PMID- 16889043
TI  - [Features of a cytokine profile in patients with chronic glomerulonephritis with
      progressive chronic renal failure].
AB  - AIM: To specify the cytokine profile in chronic glomerulonephritis (CGN) with
      aggravating renal function, to assess prognostic value of some cytokines in
      development of CGN in these patients. MATERIAL AND METHODS: Indices of the
      cytokine profile were followed up in 56 CGN patients with nephrotic syndrome and
      arterial hypertension and compared in those patients who developed CGN for 2
      years (group 2) versus patients with intact renal function (group 1). RESULTS:
      Serum levels of IL-1beta and TNF-alpha were maximal in CGN patients with
      aggravating renal function. Such patients had a low concentration of serum IL
      1beta receptors antagonists. Severity of proteinurea correlated with serum level
      of TNF-alpha. If the latter was higher than 120 pg/ml, there was a high
      probability of CRF development within 2 years. CONCLUSION: Pathogenesis of CRF in
      CGN is associated with proinflammatory cytokines, especially TNF-alpha. Its serum
      concentration can be used for evaluating risk of renal function deterioration.

PMID- 16889044
TI  - [The role of smooth muscle alpha-actin in development of renal fibrosis in
      patients with chronic glomerulonephritis].
AB  - AIM: To estimate expression of smooth muscle alpha-actin (a-SMA) in renal
      glomeruli and interstitium of patients with chronic glomerulonephritis (CGN) for
      assessment of the disease progression and prognosis. MATERIAL AND METHODS:
      Expression of a-SMA in renal tissue was studied immunohistochemically, area of
      the interstitium and the degree of its interstitial inflammatory infiltration
      were investigated morphometrically in 45 biopsy specimens of renal tissue from
      patients with different morphological types of CGN and 7 specimens of normal
      renal tissue. RESULTS: a-SMA expression in the glomeruli was higher in patients
      with proliferative morphological forms of CGN [34.3% (26.1-40.6)] than in
      patients with nonproliferative nephritis forms [22.3% (18.5-22.3)], p < 0.001; it
      was the highest in patients with sclerotic alterations in the glomeruli [55.3%
      (37-61.8)], p < 0.01. The degree of a-SMA expression in renal interstitium of CGN
      patients correlated most closely with severity of tubulo-interstitial fibrosis
      (Rs = 0.08, p < 0.001). There was no significant correlation between glomerular a
      SMA expression in renal biopsies and proteinuria, creatinine level in the serum
      of CGN patients, while a-SMA interstitial expression correlated both with
      severity of proteinuria (rs = 0.5, p < 0.05) and that of renal failure (rs = 0.7,
      p < 0.001). CONCLUSION: High expression of a-SMA in CGN occurs both in the
      glomeruli and interstitium of the kidney and evidences for activation of
      fibrogenesis but only interstitional expression can be considered as a
      morphological sign of CGN progression and as a factor of an unfavourable
      prognosis.

PMID- 16889045
TI  - [Clinical and morphological characteristics of lupus nephritis in systemic lupus
      erythematosus with antiphospholipid syndrome].
AB  - AIM: To ascertain clinical and morphological features of lupus nephritis (LN) in
      systemic lupus erythematosus (SLE) associated with antiphospholipid syndrome
      (APS). MATERIAL AND METHODS: Immunological markers of SLE and APS, clinical
      picture, urine indices were examined in 138 patients with SLE, APS and renal
      dysfunction. RESULTS: LN associated with APS is characterized with marked
      arterial hypertension, such patients had arterial thromboses more frequently than
      patients with isolated LN. Patients with anticardiolipin antibodies have
      arteriolosclerosis, in APS - diffuse interstitial sclerosis. CONCLUSION: Renal
      impairment in SLE may run not only with LN but also with thrombotic
      microangiopathy modifying clinical symptoms and course of the disease.

PMID- 16889046
TI  - [An AA-amyloidosis course in patients with rheumatoid arthritis].
AB  - AIM: To characterize renal amyloidosis in patients with rheumatoid arthritis and
      stages of amyloid nephropathy. MATERIAL AND METHODS: The trial covered 30
      patients (6 males and 24 females) with documented rheumatoid arthritis (RA)
      complicated with secondary AA-amyloidosis. Amyloidosis diagnosis was confirmed in
      all the patients morphologically, the samples were studied with the peroxidase
      immunohistochemical method using specific monoclonal antibodies to SAA. Clinical
      manifestations of RA were assessed by the disease activity, functional impairment
      of the joints, x-ray alterations, extraarticular signs of RA, etc. All the
      patients were examined clinically, total blood count and biochemical tests were
      made. RESULTS: In 23 (77%) of 30 examinees with RA, proteinuria as the first
      clinical symptom of AA-amyloidosis emerged with the first 15 years of RA. RA of
      the second-third degree of activity were diagnosed in 25 (83%) patients, 21 (70%)
      patients had apparent destructive changes in the joints (x-ray stage III-IV).
      Severe functional insufficiency of the joints was observed in 25 (83%) patients,
      deformation of the joints - in 27 (90%) patients. Clinically, renal amyloidosis
      was characterized by change of stages - from moderate proteinuria to nephrotic
      syndrome and renal failure. Prognosis of amyloid nephropathy in RA depends on
      duration of the proteinuric stage: if this stage is short (3 years maximum), the
      prognosis is worse than in its long duration. CONCLUSION: RA ranks first among
      causes of secondary AA-amyloidosis. Development of AA-amyloidosis in RA patients
      is most probable in the first 15 years of the course of the articular process.
      Amyloidosis is more frequent in patients with severe clinical manifestations of
      RA.

PMID- 16889047
TI  - [Development of renal affection in obese patients].
AB  - AIM: To characterize mechanisms, early markers and clinical signs of renal damage
      in obesity. MATERIAL AND METHODS: The trial covered 29 males aged under 50 years
      (mean age 37.7+/-9.3 years) with abdominal obesity having neither carbohydrate
      metabolism disturbances nor chronic renal disease. All the patients were examined
      for microalbuminuria (MAU), serum level of leptin. Radionuclide scintigraphy of
      the kidneys with an acute captopril test, tests for serum concentrations of
      endothelin-1, homocistein, uric acid, ultrasound dopplerography of the brachial
      artery for assessment of endothelium-related vasodilation (ERVD) were made in 24
      patients. In 9 patients MAU and ERVD were estimated after 3 months of valsartan
      treatment (80 mg/day). RESULTS: MAU was detected in 62% patients, its rate
      increasing with elevation of serum leptin and endothelin concentration. Under
      normal values of creatininemia and GFR, obese patients showed deletion of renal
      functional reserve (RFR). Patients with low RFR had maximal uricemia and
      homocysteinemia, serum endothelin-1. Such patients demonstrated also abnormal
      ERVD. 3-month valsartan intake led to elevation of ERVD and disappearance of MAU.
      CONCLUSION: Excessive leptin registered in obese patients provoked dysfunction of
      the endothelium of the intrarenal vessels manifesting with MAU, growth of
      endothelin-1 serum concentration and disorder of ERVD. This leads to unfavourable
      changes in filtrating function of the kidneys as seen from gradual deletion of
      RFR in the absence of hypercreatininemia. Elimination of MAU and ERVD disorders
      in obesity can be achieved by administration of angiotensin II receptor blockers.

PMID- 16889048
TI  - [Relationships between arterial hypertension, metabolic disturbances and uric
      acid nephropathy].
AB  - AIM: To study effects of uric acid disbolism in combination with other metabolic
      disturbances on prevalence and clinical symptoms of arterial hypertension;
      contribution of uric acid nephropathy to its development. MATERIAL AND METHODS: A
      cohort of 243 representatives from a general population (107 males, 136 females,
      age 19-59 years) was studied in 1986 and 15 years later. At the beginning and end
      of the trial the participants were examined for arterial hypertension,
      microalbuminuria, uric acid nephropathy, blood biochemical tests were made.
      RESULTS: For 15-year follow-up prevalence of arterial hypertension doubled,
      incidence of hyperuricemia and hyperuricosuria, hypertriglyceridemia increased
      considerably. The number of hypertensive subjects was maximal in the group with
      the greatest number of signs of uric acid nephropathy. CONCLUSION: The population
      studied exhibited increasing frequency of some risk factors, especially of uric
      acid metabolism, contributing to formation of arterial hypertension.

PMID- 16889050
TI  - [Structural-functional alterations in the heart affecting dynamics of transmitral
      blood flow during a hemodialysis session].
AB  - AIM: To study dynamics of transmitral circulation (TMC) during a hemodialysis
      (HD) session in patients with chronic renal failure (CRF) regarding structural
      functional alterations of the heart and baseline condition of the diastolic
      function of left ventricular (LV) myocardium. MATERIAL AND METHODS: Sixty one
      patients (34 females and 27 males, mean age 47 +/- 11 years) on programmed HD
      free of heart valvular disease, ischemic heart disease, acute myocardial
      infarction, atrial fibrillation. Before and after HD session the patients
      underwent echocardiography, including Doppler regime. RESULTS: Normal LV geometry
      was detected in 3 (4.9%) patients, concentric remodeling - in 9 (14.8%),
      concentric LV hypertrophy (LVH) - in 37 (60.7%), excentric LVH - in 12 (19.7%)
      patients. The ejection fraction was under 45% in 5 (8.2%) patients. Diastolic
      dysfunction of LV myocardium was found in 42 (68.9%) patients, TMC characteristic
      of slow relaxation was registered most frequently (47.6%). A pseudonormal type of
      TMC was recorded in 16 (38.1%) patients. HD did not change TMC significantly in
      patients with normal diastolic function (before HD E peak velocity was 88.7 +/-
      19.8 cm/s, after - 80.0 +/- 24.6 cm/s, p > 0.05). In patients with initially
      disturbed relaxation the velocity of early diastolic flow (Vp) (color M-mode
      Doppler) increased (before HD, Vp was 67.6 +/- 17.1 cm/s, after - 72.9 +/- 15.7
      cm/s, p < 0.05), E/Vp reduced (before HDm E/Vp was 1.2 +/- 0.4, after 1.0 +/-
      0.4, p < 0.05). The subgroup with initially pseudonormal TMC showed decreased
      velocity in the E peak (before HD - 103.4 +/- 13.5 cm/s, after - 76.8 +/- 24.0
      cm/s, p < 0.001). In restrictive TMC this velocity also decreased - 129.0 +/-
      17.8 cm/s and 108.8 +/- 14.7 cm/s, p < 0.05, respectively). CONCLUSION: TMC
      alteration during a HD session depends more on initial type of diastolic
      dysfunction than on LV geometry. A HD session improves intracardiac hemodynamics
      in patients with pseudonormal TMC.

PMID- 16889049
TI  - [Risk factors of vascular complications in patients at a predialysis stage of
      chronic renal failure].
AB  - AIM: To specify risk factors of vascular complications at a predialysis stage of
      renal failure. MATERIAL AND METHODS: The trial enrolled 165 patients with chronic
      renal failure (CRF) aged 46 +/- 15 years, glomerular filtration rate (GFR) - 37.2
      (35.02-40.83) and arterial hypertension (96%). The examination included
      ultrasound dopplerography of the common carotid arteries (CCA) and common femoral
      arteries (CFA) for detection of atherosclerotic plaques (AP), estimation of the
      thickness of arterial intima-media, elasticity and rigidity of the vascular wall.
      Factors of risk for atherosclerosis and cardiovascular complications were
      assessed. RESULTS: Aortic atherosclerosis was detected in 60 patients, that of
      cardiac vessels, brain, kidneys and lower limbs - in 35, 30, 23 and 8 patients,
      respectively. Acute cardiovascular complications occurred in 13 patients. Main
      atherosclerosis risk factors were age, body mass index, systolic and pulse
      arterial pressure, disturbances of phosphorus-calcium metabolism. Structure and
      function of CCA and CFA were studied with dopplerography in 37 CRF patients.
      Increased intima-media thickness was associated with age, male sex, overweight,
      hypercholesterinemia, systolic and pulse arterial pressure. Body mass index, GFR,
      creatinin level were independent factors of intima-media thickness. Abnormal
      elasticity of CCA was related to hypertension, CFA - to hypercholesterolemia.

PMID- 16889051
TI  - [Atherosclerosis/calcinosis of the carotid and peripheral arteries in patients
      with initial and terminal stages of chronic renal failure].
AB  - AIM: To perform ultrasound dopplerography (UD) investigation of severity and
      prevalence of atherosclerosis/calcinosis of the central and peripheral arteries
      in patients with chronic renal failure (CRF); to estimate correlation between the
      vascular lesions and cardiovascular risk factors. MATERIAL AND METHODS: UD of
      major arteries and echocardiography were made in 46 patients with CRF: 10
      patients with initial CRF (creatinine 1.4-2.2 mg/dl) and 36 patients with
      terminal CRF on hemodialysis. RESULTS: Calcinates and atherosclerotic plaques
      were registered in the carotid and femoral arteries of all the patients.
      Atherosclerotic lesion was more frequent than calcinosis in the carotid arteries.
      Calcinosis was more frequent in the femoral arteries. The popliteal and tibial
      arteries were affected only by calcinosis which occurred in 20% patients with
      initial and 44.4% patients with terminal CRF. Calcinosis severity increased with
      progression of CRF while atherosclerosis severity depended more on the patients'
      age than on severity of CRF. The pulse wave speed in the carotid and femoral
      arteries was higher in marked left ventricular hypertrophy, seven (19.4%) of
      these patients had reduced ejection fraction of the left ventricle < 40%.
      CONCLUSION: Compound atherosclerotic/calcinosis lesion of the vessels is
      registered at early stages of CRF and progress with progression of renal failure.

PMID- 16889052
TI  - [Risk factors of diabetic nephropathy progression in patients with a long history
      of diabetic mellitus as shown by a retrospective analysis].
AB  - AIM: To ascertain prognostic factors defining the risk of progression of diabetic
      nephropathy (DN) in patients with diabetes mellitus (DM) type 1 and 2 suffering
      from DM over 20 years. MATERIAL AND METHODS: A one-stage comparative trial
      studied 141 patients with DM type 1 and 149 patients with DM type 2 with DN of
      different severity and 20 year history of the disease. The follow-up study
      covered 34 CD-1 patients and 45 CD-2 patients with normo-, micro- and
      macroalbuminuria. The groups were made by the principle case-control. The control
      group consisted of 24 patients with DM-1 and 19 patients with DM-2 having stable
      renal function, the case group consisted of 10 and 26 patients, respectively,
      with DN progression. A total duration of the follow-up was 6 years. The end point
      of the analysis was chronic renal failure (CRF). RESULTS: Multivariate regression
      analysis has shown that the following risk factors of microalbuminuria in DM-1
      and DM-2 are independent: the level of HbA1c (RR 3,1 and 2.7, respectively) and
      duration of arterial hypertension (RR 2.1 and 2.0, respectively); proteinuria -
      HbA1c (RR 4.4 and 3.4, respectively), systolic blood pressure (RR 3.4 and 3.1,
      respectively), CRF - systolic blood pressure (RR 5.0 and 4.5, respectively),
      triglycerides (RR 2.8 and 4.9, respectively) and hemoglobin (RR 3.3 and 5.3,
      respectively). IN DM-2 other risk factors of CRF were male sex (RR 2.0), family
      history of hypertension (RR 3.8) and 24-h proteinuria > 2 g (RR 6.7). CONCLUSION:
      Inadequate compensation of carbohydrate metabolism (HbA1c), arterial hypertension
      and dyslipidemia are main risk factors of MAU and its progression to proteinuria
      in DM patients. In progression of DN to CRF main risk factors are hypertension,
      dyslipidemia and severity of anemia.

PMID- 16889053
TI  - [Combined therapy with amlodipin and lisinopril in arterial hypertension:
      efficacy of a low-dose combination].
AB  - AIM: To assess antihypertensive efficacy of a low-dose combination of amlodipin
      with lisinopril in the treatment of patients with arterial hypertension (AH) of
      the second degree. MATERIAL AND METHODS: A total of 42 patients with the second
      degree of AH (16 males, 26 females, mean age 55-9 +/- 1.9 years) entered an open,
      comparative and controlled trial. They were divided into three groups by the
      treatment. Group 1 (n = 14) received amlodipin (normodipin, Gedeon Richter)
      monotherapy in a mean dose 8.9 +/- 0.6 mg/day, group 2 (n = 12) - lisinopril
      (diroton, Gedeon Richter) in a mean dose 17.5 +/- 1.4 mg/day, group 3 (n = 16)
      was given combined therapy with amlodipin+lisinopril in a dose 6.8 +/- 0.7 and
      8.7 +/- 0.6 mg/day, respectively. The drugs were given for 12 weeks. The efficacy
      of the treatment was assessed by the results of 24-h monitoring of blood
      pressure, echocardiography, endothelium-related vasodilatation of the brachial
      artery (ERVD), dopplerographic investigation of circulation in the middle
      cerebral artery (MCA), heart rate and cost-effect estimation. RESULTS: Combined
      low-dose treatment with amlodipin and lisinopril for 12 weeks allowed achievement
      of target blood pressure in more patients and lower systolic and diastolic blood
      pressure than monotherapy with each of the drugs. There was also a positive
      effect on E/A index, ERVD, MCA circulation. CONCLUSION: Low-dose combined
      treatment with lisinopril and amlodipin is more effective and cost-efficient.
      Moreover, lisinopril addition to amlodipin corrects side effects of amlodipin on
      central nervous system.

PMID- 16889054
TI  - [Uric acid nephropathy as a cause of reversible acute renal failure in a young
      male].

PMID- 16889055
TI  - [Experience with successful administration of statins in combined therapy of
      nephrotic syndrome in a patient with AL-amy-loidosis].

PMID- 16889056
TI  - [Ischemic disease of the kidneys in a patient with morbid obesity:
      characteristics of the course and diagnostic policy].

PMID- 16889057
TI  - [Lupus nephritis: strategy and treatment].

PMID- 16889059
TI  - [C-reactive protein and arterial hypertension: are they related?].

PMID- 16889058
TI  - [Kidney involvement in sarcoidosis].

PMID- 16889060
TI  - [The VI congress of Russian Nephrology Society].

PMID- 16889061
TI  - [A new medicine for treatment of stable angina pectoris].

PMID- 16889062
TI  - [Derivatives of exemestane--synthesis and evaluation of aromatase inhibition].
AB  - The irreversible aromatase inhibitor exemestane (6) reacts with nitromethane and
      sodium ethanolate to yield the Michael adduct 9. The aldehyde 10 is obtained by
      Nef reaction of the nitro compound 9 and affords the 1,4-dihydropyridine (DHP) 11
      by Hantzsch reaction using methyl beta-aminocrotonate in acetic acid. The new
      compounds showed a reduced inhibitory potency towards aromatase (IC50 values: 9,
      0.91 microM; 10, 2.5 microM; 11, 10 microM) compared to 6 (IC50 = 0.23 microM).
      The 1,4-DHP 11 was dehydrogenated with CAN or electrochemically (E1/2 =1.18 V) to
      yield the corresponding pyridine 12.

PMID- 16889063
TI  - An efficient HPLC method for the quantification of isoflavones in soy extracts
      and soy dietary supplements in routine quality control.
AB  - Food supplements containing soy extracts are increasingly used to treat
      menopausal complaints. For the quality control of such products a RP-HPLC method
      for the quantification of daidzein, genistein, glycitein and their respective
      glucosides and acetylglucosides in soy extracts and nutraceuticals was developed
      and validated. The extraction of the samples is very simple and avoids time
      consuming handling and expensive cartridges or reagents. The compounds are
      quantified by internal standardization with 4'-hydroxyflavanon which is easily
      available at a reasonable price. On a base-deactivated C18 column good separation
      and excellent peak shape of the analytes are achieved in short time by gradient
      elution with water and acetonitrile. Accompanying substances do not interfere.
      The method was applied to the analysis of different commercial soy preparations.

PMID- 16889064
TI  - Determination and validation of ketoprofen, pantoprazole and valsartan together
      in human plasma by high performance liquid chromatography.
AB  - A rapid and specific high-performance liquid chromatographic method was developed
      and validated for the simultaneous determination of ketoprofen, valsartan and
      pantoprazole in human plasma. Chromatographic separation of ketoprofen, valsartan
      and pantoprazole was performed using a Chromasil C18 column (250 mm x 4.6 mm
      i.d., 5 microm particle size). The mobile phase consisted of a mixture of 0.02 M
      sodium dihydrogen phosphate buffer (pH 3.15) and acetonitrile (58:42, v/v) pumped
      through the chromatographic system at a flow rate of 1 mL x min(-1). The Diode
      Array detector was operated at 225 and 272 nm. Rofecoxib was used as an internal
      standard. Sample treatment procedure consisted of deproteinisation with
      acetonitrile-methanol (50:50 v/v). Analytical recoveries were in the range of
      79.00-118.00% of nominal values of valsartan, ketoprofen and pantoprazole. The
      method was reproducible and accurate with lower limits of quantification 250
      microg x L(-1) for pantoprazole and 500 microg x L(-1) for ketoprofen and
      valsartan. This method was relatively easy to perform and allows simultaneous
      determination of these three drugs in plasma at nanogram levels.

PMID- 16889065
TI  - Quantification of parthenolide in Tanacetum species by LC-UV/LC-MS and
      microscopic comparison of Mexican/US feverfew samples.
AB  - LC-UV and LC-MS methods have been developed which permit the analysis of
      parthenolide in different Mexican/US feverfew samples and commercial products.
      The study was undertaken to confirm the presence of parthenolide in Mexican plant
      samples and its comparison with US feverfew samples. The best results were
      obtained with a Phenomenex Luna C18 (2) column using gradient mobile phase of
      water and acetonitrile:methanol (9 : 1). Elution was run at a flow rate of 1.0 mL
      per min and ultraviolet detection at 210 nm. The results obtained using LC-UV
      were comparable to those obtained using LC-MS. Parthenolide was detected in all
      the samples analyzed and is the major chemical constituent of feverfew. The
      samples collected in Oaxaca, Mexico (0.28%) and Puebla, Mexico (0.25%) showed the
      highest content of parthenolide. All Parthenium samples were also examined under
      light and fluorescent microscopy.

PMID- 16889066
TI  - Increased dissolution and physical stability of micronized nifedipine particles
      encapsulated with a biocompatible polymer and surfactants in a wet ball milling
      process.
AB  - Suspensions of nifedipine, a practically water-insoluble drug, were prepared in
      the presence of a biocompatible polymer, polyvinylpyrrolidone (PVP, K value 17),
      and three surfactants, sodium lauryl sulfate (SLS, anionic),
      cetyltrimethylammonium bromide (CETAB, cationic), polysorbate 80 (Tween 80,
      nonionic), by wet milling in ceramic ball mills. Nifedipine powders encapsulated
      with PVP and the surfactants were recovered from the suspensions after milling
      and evaluated for changes in particle size, morphology, sedimentation rate in
      aqueous suspensions, crystal form, and dissolution. Particle size analysis
      indicated that milling of suspensions in solutions of PVP and surfactants is an
      efficient method for reducing the particle size of nifedipine to below 10 microm.
      Furthermore, DSC and XPS analysis indicated that during milling the nifedipine
      crystals were coated with the PVP or surfactants and that milling with PVP
      stabilized the nifedipine crystal form during milling while nifedipine was
      gradually amorphisized when milled in a quaternary nifedipine/PVP/SLS/CETAB
      system. The decrease in particle size caused a significant decrease in
      sedimentation rate and increased the dissolution rate of nifedipine in simulated
      gastric fluid when compared to milled nifedipine and powder mixtures of the drug
      and the excipients.

PMID- 16889067
TI  - Different physicochemical properties of antimycotic agents are relevant for
      penetration into and through human nails.
AB  - This article reports the characterization of the physicochemical properties of
      two important antifungal topical drugs, amorolfine and ciclopirox. Furthermore,
      the release of the drugs from commercial lacquer formulations for treatment of
      onychomycosis was studied using the online FTIR-ATR technique. Based on the
      physicochemical background of these two drugs and their release from commercial
      lacquer formulations for treatment of onychomycosis, the suitability of these
      drugs for optimized local antifungal therapy to human nails is discussed.
      Amorolfine appears to be more suitable for drug delivery to human nails because
      it penetrates into the nails via the hydrophilic pathway. Furthermore amorolfine
      penetrates very well into fungal cells, due to the pH value of the nail, as well
      as the pKa value of this antimycotic agent and the lipophilic properties of its
      base form.

PMID- 16889068
TI  - Development and in vitro evaluation of expandable gastroretentive dosage forms
      based on compressed collagen sponges.
AB  - The objective of this study was to develop and evaluate new collagen
      gastroretentive dosage forms (GRDFs) which expand in the stomach after contact
      with gastric fluids. The GRDFs should remain in the stomach for a prolonged
      period of time due to their size. The dosage forms were prepared from collagen
      sponges. The sponges were manufactured by freeze-drying a riboflavin-containing
      collagen solution. A computer controlled material supply was constructed to
      transport precompressed collagen into a tablet machine. A second type of tablet
      was manufactured by combining compressed collagen sponges with hydrophilic matrix
      layers of hydroxypropylmethylcellulose. Matrix layers containing captopril or
      aciclovir were developed. In vitro experiments were performed with both types of
      dosage forms. The collagen tablets expand within a few minutes after contact with
      artificial gastric juice and form a drug delivery system with a size of 8 mm x 18
      mm x 60 mm. Riboflavin is released over 16 h. If two layer tablets are used, the
      release of aciclovir or captopril can be controlled by the composition of the
      sustained release layer.

PMID- 16889070
TI  - Inhibition of albendazole crystallization in poly(vinylpyrrolidone) solid
      molecular dispersions.
AB  - The main aim of the study was to investigate the mechanisms of the stabilizing
      effect of poly(vinylpyrrolidone) (PVP) on amorphous albendazole (ABZ). Solid
      dispersions of ABZ with PVP polymers and with a copolymer containing
      poly(vinylacetate) (PVP/VA) were prepared using the solvent casting method. The
      effects of PVP molecular weight, composition and content on the crystallization
      of ABZ from the amorphous state were investigated using differential scanning
      calorimetry. Stability of the amorphous drug with respect to isothermal
      crystallization was studied at different polymer concentrations and storage
      temperatures. Solid dispersions were found to be X-ray amorphous and exhibited a
      single glass transition temperature (Tg). Onset of crystallization and extent of
      inhibition increased with concentration and molecular weight of the homopolymer.
      In spite of its having a higher molecular weight, replacement of about 40% of
      vinylpyrrolidone monomers with vinylacetate groups (as in the copolymer) resulted
      in reduced inhibition of crystallization. ABZ crystallized from the amorphous
      state in the absence of polymer even when stored below the Tg. The solvent
      casting method greatly reduced the requirement for polymer to achieve X-ray
      amorphous solid dispersions. Such dispersions exhibited a significant increase in
      induction time and reduction in the rate of crystallization at polymer
      concentrations as low as 5% and at temperatures as high as 70 degrees C. Factors
      other than mobility, such as drug-polymer hydrogen bonding' were also found to be
      involved in crystallization inhibition.

PMID- 16889069
TI  - Influence of microencapsulation method and peptide loading on formulation of
      poly(lactide-co-glycolide) insulin nanoparticles.
AB  - Insulin stability during microencapsulation and subsequent release is essential
      for retaining its biological activity. Therefore we investigated a novel
      solid/oil/water anhydrous encapsulation method with a combination of stabilizers
      for maintaining the integrity of insulin during formulation and delivery. Two
      methods were used for preparation of nanoparticles, namely water/oil/water
      solvent evaporation and s/o/w anhydrous encapsulation to study the influence of
      the microencapsulation method on nanoparticle characteristics such as size and
      morphology, drug content, encapsulation efficiency, and in vitro and in vivo
      release profile. Poly (lactic-co-glycolic) acid (PLGA) with co-polymer ratio
      50:50 was selected to prepare drug-loaded nanoparticles. When nanoparticles were
      prepared by solvent evaporation higher encapsulation efficiencies could be
      obtained, e.g. 74 +/- 13 with 5% target loading, whereas with 12% target loading,
      encapsulation efficiency was 27 +/- 8.6. The s/o/w method has a direct influence
      on the evaluation parameters where very poor encapsulation efficiencies 11 +/-
      6.8 (max) were observed. The presence of stabilizers in the nanoparticles
      resulted in an increase in particle size but a reduction of encapsulation
      efficiency. Insulin release rate was comparatively higher for the batches
      prepared by the w/o/w method containing stabilizers than the s/o/w method. Also
      the presence of stabilizers resulted in sustained release of insulin resulting in
      prolonged reduction of blood glucose levels in streptozotocin induced diabetic
      rats. From the in vitro and in vivo studies, it can be concluded that careful
      selection of processing conditions and combination of stabilizers also result in
      beneficial effects without compromising the advantages of these delivery systems.

PMID- 16889071
TI  - High sensitivity of chicken's skeletal muscle sarcoplasmatic reticulum to effects
      of diltiazem or verapamil on calcium uptake and release.
AB  - In this study, the effects of two different calcium channel blockers, diltiazem
      and verapamil on calcium uptake and release from the membrane of heavy
      sarcoplasmic reticulum (SR) of chicken skeletal muscle were investigated. A
      fluorescent chelate probe technique was employed to determine calcium movement
      through the SR. Chlortetracycline was used as a fluorescent indicator which is
      able to penetrate the membrane, bind to the calcium on the inner face of the
      membrane and show an increase in fluorescence intensity when calcium uptake
      occurs. Addition of tris-ATP to the microsomes caused ATP-induced calcium uptake
      in a concentration dependent manner with half-maximal calcium uptake around 0.126
      mM. Pretreatment of the medium containing sarcoplasmic reticulum with different
      concentrations of diltiazem or verapamil followed by added tris-ATP resulted a
      significant decrease in the fluorescence intensity of chlortetracycline, showing
      that these calcium channel blockers can diminish ATP-induced calcium uptake in a
      concentration-dependent manner. The maximum fluorescence intensity of tris-ATP
      falls to 50% in the presence of 1.75 microM diltiazem and 25 nM verapamil. In
      addition, diltiazem and verapamil can significantly induce rapid calcium release
      from the membrane of sarcoplasmic reticulum in a concentration-dependent manner.
      Therefore, membrane-bound or sequestered calcium in the sarcoplasmic reticulum
      may be targeted by these two calcium channel blockers in chicken skeletal muscle.
      Chicken SR is about 1000 times more sensitive to the effects of diltiazem on Ca2+
      uptake and release than rabbit SR as shown previously.

PMID- 16889072
TI  - DNA damage and oxidative stress induced by Helicobacter pylori in gastric
      epithelial cells: protection by vitamin C and sodium selenite.
AB  - The direct effect of intact Helicobacter pylori on gastric epithelial cells SGC
      7901 and the protection given by the antioxidants vitamin C and sodium selenite
      were studied. Incubation of SGC-7901 cells with H. pylori simultaneously caused a
      significant increase of DNA damage (DNA strand breakage and DNA fragmentation)
      and ROS formation, as well as a significant decrease of intracellular GSH content
      in a H. pylori multiplicity of infection (MOI) dependent manner in gastric cells.
      ROS formation was strongly positively correlated while GSH content was negatively
      correlated with DNA strand breakage and fragmentation, indicating that DNA damage
      may be mainly caused by H. pylori-induced oxidative stress in gastric cells. The
      antioxidants, vitamin C and sodium selenite, directly increased GSH content while
      diminishing ROS formation and DNA damage in H. pylori-infected SGC-7901 cells,
      indicating that vitamin C and sodium selenite can protect gastric cells against
      H. pylori damage. The protections by vitamin C and sodium selenite further
      demonstrated that DNA damage may be derived from oxidative stress in H. pylori
      infected gastric cells. The results suggested that DNA damage caused by H. pylori
      induced oxidative stress may be one important factor in the pathogenesis of H.
      pylori, and that vitamin C and sodium selenite may have a preventive or
      therapeutic role against H. pylori-associated gastric diseases.

PMID- 16889073
TI  - Genotoxic potential of Turkish propolis in peripheral blood lymphocytes.
AB  - Propolis is a natural product that is collected by the honeybee (Apis mellifera
      L.) from plants. The in vitro genotoxic potential of propolis in human
      lymphocytes was investigated. Blood samples were obtained from ten healthy (five
      female and five male), non-smoking and alcohol volunteers, which were incubated
      and exposed to increasing concentrations of propolis (5, 25, 50 and 250 mg/ml).
      The mean sister chromatid exchange (SCE) rates were 10.398 +/- 1.47-21.522 +/-
      2.08. The differences between the control and exposed cells were statistically
      significant (p < 0.05). Increasing SCE rates showed that propolis could have
      genotoxic effects in high concentrations. SCE rates of women donors exceeded
      those of men donors. Women donors had the highest SCE rates (25.674 +/- 8.71,
      22.456 +/- 7.97 and 15.756 +/- 5.09 for mean of SCE).

PMID- 16889074
TI  - Phenolic glycosides from Exostema mexicanum leaves.
AB  - Phytochemical investigation of the leaves of Exostema mexicanum led to the
      isolation of two novel acylated flavonol glycosides 6, 7 and three glycosides 1-4
      structurally belonging to the group of 4-phenylcoumarins. One of them, 5-O-beta-D
      glucopyranosyl-4'-hydroxy-7-methoxy-4-phenylcoumarin (2), turned out to be new.
      Furthermore, the 4-phenylcoumarin aglycone 3'-hydroxy-4',5,7-trimethoxy-4
      phenylcoumarin (5) was obtained. The in vitro cytotoxicity of 3-5 against the
      cell line ECV-304 was evaluated; the aglycone 5 was highly cytotoxic, whereas the
      glycosidic compounds 3 and 4 were inactive.

PMID- 16889075
TI  - New polyoxygenated steroids from the South China Sea gorgonian Echinogorgia
      aurantiaca.
AB  - Three new polyoxygenated steroids, named 3beta,7alpha,9alpha-trihydroxy-cholestan
      6-one (1), 3beta,5alpha,6beta-trihydroxycholestan-1-one (2) and cholestane
      3beta,5alpha,6beta,11beta-tetrol (3), along with four known steroids (4-7) were
      isolated from the South China Sea gorgonian Echinogorgia aurantiaca. The
      structures of 1-3 were established by extensive spectroscopic analysis, including
      1D and 2D NMR data.

PMID- 16889076
TI  - Synthesis of gem-difluoromethylenated daidzein analogues and their inhibitory
      effect on U2OS cell cycle.
AB  - gem-Difluoromethylenated daidzein analogues 2 and 4 were obtained by the
      insertion reaction of difluorocarbene. A series of alkylated fluorine-containing
      daidzein analogues 3a-f and 5a-f were synthesized. All the compounds were tested
      for the inhibitory effect on U2OS cell cycle in vitro. The results showed that 7
      octyloxy-3-(4-difluoromethoxyphenyl)-chromen-4-one 5d was the most active
      inhibitor.

PMID- 16889077
TI  - Microemulsions with timolol as potential eye drops.
AB  - Stable microemulsions oil-in-water (o/w) and water-in-oil (w/o) with timolol were
      obtained. These formulations were sterilized using two methods: by autoclaving
      and by sterile filtering according to the Polish Pharmacopeia V. Microemulsions
      were kept in the temperatures of 25 degrees C and 5 degrees C during three
      months. The following physical parameters were investigated: density, dynamic
      viscosity, refractive index, surface tension, pH and osmotic tension. All the
      microemulsions met the requirements for eye drops.

PMID- 16889078
TI  - Absorption of myo-inositol hexakisphosphate (InsP6) through the skin in humans.
AB  - In this paper, we present a pilot study of the absorption of myo-inositol
      hexakisphosphate (InsP6) through the skin in humans. We found that, after topical
      treatment with a 4% InsP6 rich gel, InsP6 urinary excretion increased 54%
      compared to the control situation (participants submitted to an InsP6-poor diet
      for 15 days, n = 6), clearly demonstrating that InsP6 is absorbed through the
      skin of humans. These results demonstrate the topical application as a suitable
      administration route of InsP6 in humans.

PMID- 16889079
TI  - Lawsuit follows new Medicaid citizenship documentation rule.

PMID- 16889081
TI  - [Transurethral electroresection of prostatic adenoma under transrectal ultrasonic
      control].
AB  - The aim of the study was to improve the results of transurethral prostatic
      resection (TUPR) by introduction of intraoperative transrectal ultrasonic
      investigation (TRUSI) and to determine topographic-anatomic features of the
      prostate, intraorgan relations of adenomatous nodes and surgical prostatic
      capsule on-line in TUPR. A total of 64 patients with prostatic adenoma (PA) of
      the second degree aged 52-79 participated in the study. All of them have
      undergone TUPR. The patients were divided into two study groups (15 patients with
      volume of the prostate 36.5-78.6 cm3 and 17 patients with prostate size 80-4
      141.2 cm3) in which TRUSI was performed and two control groups (n = 14, size 34.9
      to 79.2 cm3 and n = 18, size 81.7-130.8 cm3, respectively) who have not undergone
      intraoperative TRUSI. PA clinical symptoms were similar in all the groups.
      Intraoperative TRUSI was conducted in 3 stages (in the beginning, middle and end
      of surgery) in two planes--transverse and sagittal. Postoperative complications
      required repeated endoscopic interventions in 2 and 4 patients of groups 2, 3 and
      4, respectively. Control TRUSI on day 7 after TUPR registered mean volume of the
      prostate to be 19.3 +/- 1.4 cm3 in group 1, 39.8 +/- 2.1 cm3 in group 2, 28.1 +/-
      1.6 cm3 in group 3, 47.7 +/- 3.2 cm3 in group 4. Maximal flow rate 1 month after
      TUPR was, on the average, 21.4 +/- 1.4 ml/s, 18.8 +/- 1.1 ml/s, 18.3 +/- 1.6 ml/s
      and 15.5 +/- 1.2 ml/s in groups 1, 2, 3 and 4, respectively. Thus, intraoperative
      TRUSI provides information which helps the surgeon to orient in the course of
      surgery and minimize the threat of perforation of the prostatic capsule;
      minimizes intraoperative complications and enhances efficacy of radical
      transurethral electroresection of prostatic hyperplasia improving long-term
      outcomes of the operation.

PMID- 16889080
TI  - [Pilot results of using tamsulone-FS in patients with prostatic adenoma according
      to the results of a randomized multicenter comparative trial].
AB  - Tamsulone-FS--a novel Russian alpha1A/D-adrenoblocker (Farm-Syntez)--was studied
      in a randomized multicenter comparative trial in patients with prostatic adenoma.
      Pilot results agreed with other trials published in the literature and
      demonstrated tamsulone-FS efficacy and safety for management of lower urinary
      tract symptoms caused by prostatic adenoma. The efficacy and safety of tamsulone
      FS was comparable to those of omnik. This drug can be recommended for wide
      clinical practice in prostatic adenoma. It is registered by Roszdravnadzor
      (certificate N LC-000859 of 03.11.2005) and allowed for production and sale.

PMID- 16889083
TI  - [Local recurrence of renal cell carcinoma after radical nephrectomy].
AB  - Radical nephrectomy was made in 483 patients with renal cell carcinoma (RCC)
      without metastases admitted to National Urology Center in 1989-2004. Isolated
      local recurrence was observed in 10 (2.07%) patients who were divided into two
      groups. The recurrent tumor was removed in 6 patients of group 1, four patients
      of group 2 received conservative treatment. Statistic processing was made with
      Kolmogorov-Smirnov test and unmatched t-test. Survival was estimated according to
      Kaplan-Meyer, significance of the differences--by log rank test. Three patients
      of group 1 died of progression of basic disease. Only 1 patient from group 2 was
      alive 22 months after detection of the recurrence. Mean survival in group 1 was
      27.5 +/- 14.9 months, in group 2--10 +/- 8.5 months (p = 0.045). A mean size of
      the recurrent tumor in survivors was 5.4 +/- 2.1 cm, while in dead patients-
      10.05 +/- 2.76 cm (p = 0.02). Radicalism of the recurrent tumor removal
      influenced survival of the patients (p = 0.019). In survivors local recurrence
      developed 35.7 +/- 28.1 months after radical nephrectomy; in the deceased the
      recurrence arose 23.3 +/- 25.5 months after nephrectomy (p = 0.46). Thus, early
      detection of isolated local recurrence of a relatively small size allows complete
      recovery in some surgically treated patients.

PMID- 16889082
TI  - [Transurethral plasmokinetic resection and vaporization is a new method of
      treatment of prostatic adenoma].
AB  - Clinical efficacy and safety ofplasmakinetic resection and vaporization were
      studied in 28 patients with prostatic adenoma (mean age 68 years, mean size of
      the prostate 65 cm3). Complaints by IPSS scale, quality of life index, results of
      uroflowmetry and prostatic ultrasonography were assessed before surgery
      (transurethral plasmakinetic resection and prostatic vaporization) and 1, 3, 6
      and 12 months after it. Twenty-five and 15 patients after 6 and 12 months after
      the operation were examined with the following results: IPSS was 6 scores, on the
      average (22.5 scores before the operation), quality of life index--3.1 (5.3
      scores). Qmax was in 3 months 20 ml/s, on the average (7.5 ml/s), residual urine
      was under 35 ml (130.7 ml). Pilot results point to high clinical efficacy and
      safety of plasmakinetic resection and vaporization in patients with prostatic
      adenoma. Therefore, further studies of the method and accumulation of clinical
      experience are necessary.

PMID- 16889084
TI  - [Comparative value of molecular forms of prostate-specific antigen in diagnosis
      of prostatic cancer].
AB  - The aim of the study was to compare diagnostic significance of free PSA
      (fPSA)/total PSA (tPSA) versus PSA complex with alpha1-antichymotrypsin (cPSA) in
      tPSA level within 4-10 ng/ml in differential diagnosis of prostatic cancer (PC).
      A complete urological examination (digital rectal test, transrectal ultrasound
      investigation, serum assay for fPSA and tPSA, multifocal transperineal prostatic
      biopsy) was made in 108 patients with tPSA blood level 4-10 ng/ ml. Prostatic
      adenoma (PA) was histologically verified in 61 of 108 patients, fPSA/tPSA was
      normal. In the other 39 of 108 patients fPSA/tPSA was under 15% while cPSA was in
      the range 3.8-9.6 ng/ml. A course of etiotropic therapy of chronic prostatic
      inflammation produced no significant changes in fPSA/tPSA and cPSA in 28 out of
      39 patients. Histologically, these 28 patients had PC. In the rest 11 of 39
      patients chronic prostatitis treatment fPSA/tPSA significantly rose to 18.2%, on
      the average. CPSA decreased to 2.4 ng/ml. These 11 patients were found
      histologically to have PA and signs of chronic inflammation. In 8 of 108 patients
      fPSA/tPSA was not indicative of PC being 18,2% on the average while cPSA
      indicated the presence of PC and was 4.2 ng.ml, on the average. PC was verified
      histologically in these 8 patients. Thus, cPSA in PC suspects is more informative
      than fPSA/tPSA in PC diagnosis. CPSA in the serum depends on prostatic
      inflammation making difficult differential diagnosis of PC in interpretation of
      tPSA, fPSA/tPSA and cPSA. Therefore, estimation of PSA variants and molecular
      forms in PC suspects and prostatic inflammation should be made after etiotropic
      therapy.

PMID- 16889085
TI  - [Photodynamic therapy of urinary bladder cancer using a chlorin based
      photosensitizer].
AB  - Photodynamic therapy (PDT) is a modem, low-invasive method of urinary bladder
      (UB) cancer treatment. PDT can induce complete or partial destruction of the
      tumor, reduce recurrence rate, provide assistance to elderly patients with
      compromised somatic status who are not radically operable. A combined technique
      improves the results of photodynamic therapy in patients with surface and
      invasive UB cancer of stage T2 because photodynamic impact affects not only the
      tumor but also all UB mucosa by light fiber with cylindric diffusor introduced in
      a silicon balloon with water. This leads to tumor destruction and a recurrence
      rate decrease.

PMID- 16889086
TI  - [Urgent problems of prostatic cancer diagnosis in a small district clinic].
AB  - Diagnostic methods in prostatic pathology used in a surgical department of a
      small town of Pavlovo (Nizhny Novgorod Region) are analysed. Infrared
      spectroscopy was for the first time used in Pavlovo for diagnosis of cancer.
      Examination of 57 patients aged 38-89 years has detected prostatic cancer in 16
      (28 +/- 5.9%) patients, chronic prostatitis in 6 (10.5 +/- 4%) patients,
      prostatic adenoma in 34 (59.6 +/- 6.4%) patients, prostatic abscess--in 1 (1.9 +/
      1.7%) patient. Infrared spectroscopy of the blood serum according to the
      proposed technique provides accurate (91.2 +/- 4.8%, p < 0.01) differential
      diagnosis of benign and malignant diseases of the prostate.

PMID- 16889087
TI  - [Extended lymphadenectomy in radical cystectomy: margins, scope, methodology].
AB  - Radical cystectomy with pelvic lymphadenectomy is a gold standard for treatment
      of muscle-invasive urinary bladder cancer. However, therapeutic and prognostic
      value of pelvic lymphadenectomy is still controversial. Recent studies have
      demonstrated a better prognosis after extended lymphadenectomy. A multicenter
      study was made to standardize an extended lymphadenectomy procedure. We examined
      prospectively the total number of lymph nodes removed from various sites, number
      and location of positive nodes and its relation to location of primary tumors in
      the urinary bladder. Thirty five radical cystectomies with extended
      lymphadenectomy were performed for the treatment of invasive bladder cancer in
      National Urology Center in 1999-2004. The margins of extended lymphadenectomy
      were: cranial level of a.mesenterica inferior; lateral--n.n. genitofemoralis;
      caudal-fossa obturatoria. A total amount of removed lymph nodes comprised 1081,
      mean 34.2 +/- 8.1 lymph node per patient (range from 10 to 58). Fourteen patients
      (40.0%) were node positive (69 nodes). According to N category: N1--6 patients;
      N2--7 patients. Six patients had lymph node metastases up to the aortic
      bifurcation. In 6 cases a positive node was found on the contralateral side.
      Thus, we recommend extended radical lymphadenectomy for all patients undergoing
      radical cystectomy for bladder cancer.

PMID- 16889088
TI  - [Cancer of the urinary bladder and prostatic gland in Kalmykia].
AB  - The article presents data on prevalence of urological cancer in Kalmykia by
      environmental zones and among males and females. In 1998 urological cancer
      accounted for 18.6% of all cancer cases. Urinary system cancer occurred in 6.8%
      of all cancer cases in the republic in 1997, prostatic cancer was encountered in
      31.7%. In the recent decade prostatic cancer morbidity has risen from 6.9 to 16.9
      per 100000, while the rate of advanced cases of urological cancer decreased.
      Transrectal ultrasonic investigation, puncture biopsy of the prostate, assay for
      PSA are among available diagnostic methods.

PMID- 16889089
TI  - [Experimental study of the effects of impulse-electric discharge on chemotaxis
      and cytoadhesion of urinary infection pathogens].
AB  - The aim of the experimental study was to evaluate effects of impulse-electric
      discharge in liquid on chemotaxis and cytoadhesion of urinary infection
      pathogens. Chemotaxis was determined in respect to the lung, liver, spleen,
      kidney, ureter, urinary bladder, urethra of white mice by S. Likholetov's
      modified method. Cytoadhesion was assessed by V. Brilis. The experiments show
      that the impulse-electric discharge holds promise for urological practice.

PMID- 16889090
TI  - [The kidneys and their vascular system in deficient inflow of arterial blood (an
      experimental study)].
AB  - Structural alterations of the kidneys and their vascular system were studied in
      condition of arterial circulation deficiency induced by narrowing of the isthmus
      of the aorta in 30 pups. The animals were followed up from 6 to 24 months. The
      model of chronic renal ischemia was achieved in which there was a fall in blood
      flow in the descending aorta and in pressure of blood coming to the kidneys. The
      capacity of the arterial part of the renal circulation with reactive thinning of
      the walls of renal arteries of different caliber was diminished. Adaptation of a
      part of these vessels caused closure rearrangement and decreased blood filling of
      glomerular capillaries with collaboration of some of them. The capacity of renal
      venous collectors increased due to blood deposit. Sclerotic changes of renal
      arteries, veins and glomeruli, atrophy of renal parenchyma, stromal overgrowth
      developed with time.

PMID- 16889091
TI  - [Influence of low intensive laser irradiation on ultrastructural changes in
      kidney tissue in experimental colic].
AB  - This investigation aimed at estimation of the influence of low-intensive laser
      irradiation on ultrastructural changes in renal tissue according to electronic
      microscopy data in case of experimental renal colic. The experiment was made on
      twenty rabbits with a single or recurrent colic. Ten animals after a single colic
      were exposed to low intensive laser therapy. Electronic microscopy showed that
      single renal colic is associated with marked ultrastructural changes in the
      proximal tubules. In recurrent colic the edema and destruction were more
      expressed in all nephron parts. Low intensive laser irradiation suppresses
      pathological processes in nephrocytes both after a single renal colic and after a
      recurrent renal colic; has a systemic effect on the body; stimulates compensatory
      processes in the contralateral kidney.

PMID- 16889092
TI  - [Endoprosthesis of the ureter].
AB  - A stent made of titanium nikelide monothread was used in the treatment of 37-63
      year old male patients with recurrent and long strictures of the ureters. A metal
      stent was used in 3 patients with recurrent and long structures of the ureter. A
      long pyeloureteral stricture developed in two patients with allotransplanted
      kidney after several operations. The stricture in one patient was caused by a
      failed resection of the pyeloureteral segment and subsequent attempts of
      endoscopic correction of the upper urinary tract. Metal stents were used in all
      the cases. No serious postoperative complications were observed. The operations
      were effective. No lethal outcomes occurred. Follow-up for 6 to 13 months stated
      normalization of urodynamics and function of the affected kidney. Thus, a metal
      stent in some cases of recurrent and long ureteral strictures reestablishes
      passability of the upper urinary tract and improves quality of life.

PMID- 16889093
TI  - [Vesicoureteral reflux in renal transplantation].
AB  - Frequency of vesicoureteral reflux (VUR) variants was studied with miction
      cystography in 40 patients with chronic renal insufficiency. In 8 (20%) patients
      VUR was in their kidneys. The kidney was transplanted in 30 patients. The rate of
      urological complications was compared in ureterocystostomy by our technique and
      other procedures. In patients operated by our technique VUR did not occur. In 3
      of 10 patients operated by other methods VUR into the transplant was found. Own
      kidney on the side of the reflux was removed in 4 patients after kidney
      transplantation. Indication for removal of own kidneys after allotransplantation
      of the kidney is urinary infection, arterial hypertension, pain in the lumbar
      spine. The proposed technique of ureterocystostomy has advantages in prevention
      of VUR into the renal transplant.

PMID- 16889094
TI  - [Efficacy of a plant complex Prolit after extracorporeal lithotripsy in patients
      with urolithiasis].
AB  - A study of an additive prolit efficacy was made in the urological clinic of Kazan
      State Medical University. All the examinees were divided into two groups: 20
      patients of group 1 were exposed to extracorporeal lithotripsy (EL) followed by
      conventional postoperative conservative therapy, 22 patients of group 2 received
      EL plus prolit. The latter was able to reduce twice the time of concrement
      elimination from the urinary tract after EL, to lower leukocyturia from 86.4 to
      18% and bacteriuria from 50 to 13.6%, renal colic rate and risk of stone path
      after EL, to improve renal blood flow and to reduce the risk of traumatic
      parenchymal damage due to the shock wave impact in EL.

PMID- 16889095
TI  - [Tuberculosis of the urinary bladder: diagnosis and treatment].
AB  - Tuberculosis of the urinary bladder (UB) is registered in 10-45.6% patients with
      urogenital tuberculosis. It is a severe incapacitating complication of kidney
      tuberculosis which significantly lowers quality of life. The results of the
      standard therapy of 76 patients with tuberculous cystitis are analysed. UB
      tuberculosis is diagnosed more often in women, outcomes of their treatment are
      worse. Twenty six patients with UB tuberculosis at the stage of overactive
      bladder received polychemotherapy and adjuvant trospium. After 3 months urination
      frequency decreased 4.3 times, on the average; UB volume increased 4.7 times, on
      the average. Complications were not registered.

PMID- 16889096
TI  - [Premature ejaculation: diagnosis, classification, algorithm of the patients'
      examination and results of their application].
AB  - We have analysed literature data and own experience with management of premature
      ejaculation (PE) in 3200 patients. This gave grounds for formulation of this
      phenomenon, creation of the classification and the examination algorithm. We
      applied the proposed methods in the treatment of 258 PE patients and made the
      conclusion about their adequacy and efficacy. PE is a polyetiological phenomenon
      and a multidisciplinary problem. Urological examination must be used as the first
      stage of the diagnostic process.

PMID- 16889097
TI  - [Advantages of the use of Andro-Gin device for treatment of secretory
      infertility].
AB  - The trial included 144 patients aged from 24 to 46 years with secretory
      infertility in the presence of chronic prostatitis of 2 to 13 year duration. The
      study group consisted of 96 patients who received conventional treatment in
      combination with physical factors provided by the unit APK-ELM-01 Andro-Gin. The
      control group consisted of 48 patients on conventional treatment alone. The
      results were processed mathematically and statistically. The patients were
      examined before, 2 weeks, 1 and 6 months after the treatment. Positive response
      was greater in the study group: better parameters of prostatic secretion,
      spermogram. Normalization of all the parameters occurred in 95 and 80% patients
      of the study and control groups, respectively. Thus, Andro-Gin is effective for
      treatment of chronic prostatitis with secretory infertility.

PMID- 16889098
TI  - [Clinicoimmunological disorders in patients with chronic prostatitis caused by
      latent urogenital infection].
AB  - The study enrolled 506 males 20 to 50 years of age (mead age 30.8 +/- 0.5 years)
      with chronic prostatitis (CP). Group 1 consisted of 332 (65 +/- 4.1) patients
      with CP caused by lateral urogenital infection (LUGI) due to chlamydias,
      ureaplasmas, mycoplasmas, gardnerellas, herpes virus type 2. Group 2 comprised
      174 patients free of LUGI. T-cell and humoral immunity parameters were assessed
      by T-lymphocytes CD3, T-helpers CD4, T-suppressors CD8, CD4/CD8, natural killer
      cells CD16 using indirect immunofluorescence. Phagocytic activity of T
      lymphocytes was estimated with latex as the antigen. An etiological factor was
      ureaplasmas, chlamydias and others in 170 (51.2 +/- 5.4%) and 155 (46.7 +/- 5.4%)
      patients, respectively. Mixed infection was diagnosed in 94 (28.3 +/- 4.8%)
      patients. Secondary immune and interferon deficiencies were detected in 155
      (30.6%) patients of both groups. The patients received etiological
      (antimicrobial) and pathogenetic (immunological) therapy. The highest effect was
      obtained in prostatitis caused by mono-LUGI. Pain and pollakiuria attenuated, the
      copulative function improved. The conclusion is made that CP, especially
      secondary to LUGI, should be treated by combination of etiotropic with
      immunotropic methods.

PMID- 16889099
TI  - [Invagination vasoepididymoanastomosis with application of microsurgical tools].
AB  - A variant of microsurgical invagination vasoepididymostomy (patent of the Russian
      Federation N 2195205, 2002) was developed in 2001-2004 in experiment on 21
      mongrel dogs. Fourteen dogs have undergone 22 vasoepididymostomies according to
      the novel technique and 5 control vasoepididymoanastomoses side-to-side. The
      proposed operation implies deep antegrade submersion and fixation of the stump of
      the epididymis duct in the lumen of the deferent duct through a small slit wound
      of the latter. Duration of the operation is 62 +/- 3 min. Passability of the
      anastomosis was assessed 6 months after the operation with ejaculate microscopy,
      retrograde staining of the deferent ducts on the preparations and with microscopy
      of stained histological sections. Spermatozoa were detected in ejaculate of all
      the operated on dogs. By microscopy, 20 anastomoses were capable. This operation
      technique was introduced into clinical practice: 3 patients with epididymic
      obstruction were operated on. Passability recovered 1.5-2 months after the
      operation in two of them. Thus, this variant of invagination vasoepididymostomy
      is perspective for wide clinical practice.

PMID- 16889100
TI  - [Comparative characteristics of testosterone preparations for androgen-replacing
      therapy in male hypogonadism].

PMID- 16889101
TI  - [Quality of life in prostatic cancer].

PMID- 16889102
TI  - Various forms of depression.
AB  - The current subtyping of depression is based on the Diagnostic and Statistical
      Manual of Mental Disorders, 4th ed, Text Revision (DSM-IV-TR) categorical
      division of bipolar and depressive disorders. Current evidence, however, supports
      a dimensional approach to depression, as a continuum/spectrum of overlapping
      disorders, ranging from bipolar I depression to major depressive disorder. Types
      of depression which have recently been the focus of most research will be
      reviewed: bipolar II depression, mixed depression, agitated depression, atypical
      depression, melancholic depression, recurrent brief depression, minor depressive
      disorder, seasonal depression, and dysthymic disorder. Most research has focused
      on bipolar II depression, mixed depression (defined by depression and
      superimposed manic/hypomanic symptoms), and atypical depression. Mixed
      depression, by its combination of opposite polarity symptoms, has been found to
      be common by systematic probing for co-occurring manic/hypomanic symptoms. Mixed
      depression is a treatment challenge for clinicians, because antidepressants alone
      (ie, not protected by mood-stabilizing agents) may worsen its manic/hypomanic
      symptoms, such as irritability and psychomotor agitation, which the Food and Drug
      Administration (FDA) has listed as possible precursors to suicidality.

PMID- 16889103
TI  - Changes in the immune system in depression and dementia: causal or coincidental
      effects?
AB  - Epidemiological studies show that there is a correlation between chronic
      depression and the likelihood of dementia in later life. There is evidence that
      inflammatory changes in the brain are pathological features of both depression
      and dementia. This suggests that an increase in inflammation-induced apoptosis,
      together with a reduction in the synthesis of neurotrophic factors caused by a
      rise in brain glucocorticoids, may play a role in the pathology of these
      disorders. A reduction in the neuroprotective components of the kynurenine
      pathway such as kynurenic acid, and an increase in the neurodegenerative
      components, 3-hydroxykynurenine and quinolinic acid, contribute to the
      pathological changes. Such changes are postulated to cause neuronal damage, and
      thereby predispose chronically depressed patients to dementia.

PMID- 16889106
TI  - Rating scales in depression: limitations and pitfalls.
AB  - Since the introduction of antidepressants to psychopharmacology in the 1960s, the
      Hamilton Depression Rating Scale (HAM-D) has been the most frequently used rating
      scale for depression. When used as a scale for prediction of outcome with
      antidepressants, the HAM-D, by its total score, has obtained limited use
      analogous to the Diagnostic and Statistical Manual of Mental Disorders. 4th ed
      (DSM-IV) diagnosis of major depression. Most research has been devoted to the use
      of the HAM-D to discriminate between placebo and active drugs or to show dose
      response relationship in patients with major depression. An improvement in the
      total HAM-D score during a drug trial does not, however, in itself qualify the
      drug as an antidepressant, because the total score is not a sufficient statistic.
      The problem of statistical versus clinical significance when analyzing placebo
      controlled trials, including dose-response relationship, is outlined, with the
      recommendation to use effect size statistics.

PMID- 16889104
TI  - Future prospects in depression research.
AB  - Major depression is a common, disabling, and often difficult-to-treat illness.
      Decades of research into the neurobiology and treatment of depression have
      greatly advanced our ability to manage this disorder. However, a number of
      challenges remain. A substantial number of depressed patients do not achieve full
      remission despite optimized treatment. For patients who do achieve resolution of
      symptoms, depression remains a highly recurrent illness, and repeated episodes
      are common. Finally, little is known about how depression might be prevented,
      especially in individuals at increased risk. In the face of these challenges, a
      number of exciting research efforts are currently under way and promise to
      greatly expand our knowledge of the etiology, pathophysiology, and treatment of
      depression. This review highlights these future prospects for depression research
      with a specific focus on lines of investigation likely to generate novel, more
      effective treatment options.

PMID- 16889105
TI  - Treatments in depression.
AB  - Major depression is believed to be a multifactorial disorder involving
      predisposing temperament and personality traits, exposure to traumatic and
      stressful life events, and biological susceptibility. Depression, both unipolar
      and bipolar, is a "phasic" disease. Stressful life events are known to trigger
      depressive episodes, while their influence seems to decrease over the course of
      the illness. This suggests that depression is associated with progressive stress
      response abnormalities, possibly linked to impairments of structural plasticity
      and cellular resilience. It therefore appears crucial to adequately treat
      depression in the early stages of the illness, in order to prevent morphological
      and functional abnormalities. While evidence suggests that a severely depressed
      patient needs antidepressant drug therapy and that a non-severely depressed
      patient may benefit from other approaches (ie, "nonbiological"), little research
      has been done on the effectiveness of different treatments for depression. The
      assertion that the clinical efficacy of antidepressants is comparable between the
      classes and within the classes of those medications may be true from a
      statistical viewpoint, but is of limited value in practice. The antidepressant
      drugs may produce differences in therapeutic response and tolerability. Among the
      possible predictors of outcome in depression treatment, those derived from
      clinical assessment, neuroendocrine investigations, polysomnographic sleep
      parameters, genetic variables, and brain imaging techniques have been extensively
      studied. This article also reviews therapeutic strategies used when initial
      treatment fails, and describes briefly new concepts in antidepressant therapies
      such as the regulation of disturbances in circadian rhythms. The treatment of
      depressive illness does not stop with treatment of acute episodes, and has to be
      envisaged as a continuous therapeutic intervention, of which we are still not
      able to determine the optimal duration of treatment and the moment that it should
      be ceased.

PMID- 16889107
TI  - Depression and sleep: pathophysiology and treatment.
AB  - This review examines the relationship between sleep and depression. Most
      depressive disorders are characterized by subjective sleep disturbances, and the
      regulation of sleep is intricately linked to the same mechanisms that are
      implicated in the pathophysiology of depression. After briefly reviewing the
      physiology and topography of normal sleep, the disturbances revealed in studies
      of sleep in depression using polysomnographic recordings and neuroimaging
      assessments are discussed. Next, treatment implications of the disturbances are
      reviewed at both clinical and neurobiologic levels. Most antidepressant
      medications suppress rapid eye movement (REM) sleep, although this effect is
      neither necessary nor sufficient for clinical efficacy. Effects on patients'
      difficulties initiating and maintaining sleep are more specific to particular
      types of antidepressants. Ideally, an effective antidepressant will result in
      normalization of disturbed sleep in concert with resolution of the depressive
      syndrome, although few interventions actually restore decreased slow-wave sleep.
      Antidepressants that block central histamine 1 and serotonin 2 tend to have
      stronger effects on sleep maintenance, but are also prone to elicit complaints of
      daytime sedation. Adjunctive treatment with sedative hypnotic medications-
      primarily potent, shorter-acting benzodiazepine and gamma-aminobutyric acid (GABA
      A)-selective compounds such as zolpidem--are often used to treat associated
      insomnia more rapidly. Cognitive behavioral therapy and other nonpharmacologic
      strategies are also helpful.

PMID- 16889108
TI  - Somatic symptoms in depression.
AB  - Both painful and nonpainful somatic symptoms essentially characterize clinical
      states of depressive mood. So far, this well-established psychopathological
      knowledge has been appreciated only insufficiently by the official diagnostic
      systerms of the Diagnostic and Statistical Manual of Mental Disorders, 4th
      edition, Text Revision (DSM-IV TR) and the ICD-10 Classification of Mental and
      Behavioral Disorders. Clinical Descriptions and Diagnostic Guidelines (ICD-10).
      From a perspective of primary care services, this unmet diagnostic need is
      deplorable, as the main mode of presenting a depression is by reporting somatic
      symptoms. This somatic form of presentation, however, significantly contributes
      to low rates of recognition in primary care. A diagnostic challenge may be seen
      in the differentiation of a depression with prevailing somatic symptoms from
      anxiety, somatoform disorders, and medical conditions. When somatic symptoms,
      particularly painful physical conditions, accompany the already debilitating
      psychiatric and behavioral symptoms of depression, the course of the illness may
      be more severe, implying a higher risk of early relapse, chronicity, suicide, or
      mortality due to other natural causes, the economic burden increases considerably
      the functional status may be hampered heavily, and health-related quality of life
      may be lowered dramatically. The neurobiological underpinnings of somatic
      symptoms in depression may guide more promising treatment approaches.

PMID- 16889110
TI  - Depression and associated physical diseases and symptoms.
AB  - Depression can occur in association with virtually all the other psychiatric and
      physical diagnoses. Physical illness increases the risk of developing severe
      depressive illness. There are two broadly different mechanisms. The most obvious
      has a psychological or cognitive mechanism. Thus, the illness may provide the
      life event or chronic difficulty that triggers a depressive episode in a
      vulnerable individual. Secondly, more specific associations appear to exist
      between depression and particular physical disorders. These may turn out to be of
      particular etiological interest. The best examples are probably stroke and
      cardiovascular disease. Finally, major depression, but especially minor
      depression, dysthymia, and depressive symptoms merge with other manifestations of
      human distress with which patients present to their doctors. Such somatic
      presentations test the conventional distinction between physical and mental
      disorder and are a perennial source of controversy.

PMID- 16889112
TI  - Occupational risk: the outrageous reaction to HIV positive public safety and
      health care employees in the workplace.

PMID- 16889111
TI  - Community health centers: health care as it could be.

PMID- 16889113
TI  - The doctor will e-mail you now: physicians' use of telemedicine to treat patients
      over the Internet.
AB  - This article examines the problems currently associated with the practice of
      telemedicine and suggests that the best solution for this particular field of
      medicine is a national standard of care. This article also suggests that the Food
      and Drug Administration's (FDA) current functions are easily expandable to the
      telemedicine context; therefore, the agency should regulate the implementation of
      such a standard in the telemedicine field. This article proposes that the FDA use
      medical practice guidelines in developing the applicable standard. Other
      agencies, such as the American Medical Association (AMA) and other website
      alliances, could also aid the FDA in implementing this standard because of their
      experience in setting such guidelines for the traditional medical context.
      Finally, this article suggests that in implementing the national standard of
      care, the FDA should increase the standard of care that telephysicians, as
      compared to traditional physicians, owe their patients because of the risks
      associated with treating patients in the absence of hands-on consultations. By
      implementing a national standard of care, problems currently associated with
      telemedicine will be resolved, and physicians and patients will have more
      confidence in telemedicine.

PMID- 16889109
TI  - Nonpharmacological, somatic treatments of depression: electroconvulsive therapy
      and novel brain stimulation modalities.
AB  - Until recently, a review of nonpharmacological, somatic treatments of psychiatric
      disorders would have included only electroconvulsive therapy (ECT). This
      situation is now changing very substantially. Although ECT remains the only
      modality in widespread clinical use, several new techniques are under
      investigation. Their principal indication in the psychiatric context is the
      treatment of major depression, but other applications are also being studied. All
      the novel treatments involve brain stimulation, which is achieved by different
      technological methods. The treatment closest to the threshold of clinical
      acceptability is transcranial magnetic stimulation (TMS). Although TMS is safe
      and relatively easy to administer, its efficacy has still to be definitively
      established. Other modalities, at various stages of research development, include
      magnetic seizure therapy (MST), deep brain stimulation (DBS), and vagus nerve
      stimulation (VNS). We briefly review the development and technical aspects of
      these treatments, their potential role in the treatment of major depression,
      adverse effects, and putative mechanism of action. As the only one of these
      treatment modalities that is in widespread clinical use, more extended
      consideration is given to ECT Although more than half a century has elapsed since
      ECT was first introduced, it remains the most effective treatment for major
      depression, with efficacy in patients refractory to antidepressant drugs and an
      acceptable safety profile. Although they hold considerable promise, the novel
      brain stimulation techniques reviewed here will be need to be further developed
      before they achieve clinical acceptability.

PMID- 16889114
TI  - The mentally ill offender: a brighter tomorrow through the eyes of the Mentally
      Ill Offender Treatment and Crime Reduction Act of 2004.

PMID- 16889115
TI  - How Ohio v. Talty provided for future bans on procreation and the consequences
      that action brings: Ohio v. Talty: hiding in the shadow of the Supreme Court of
      Wisconsin.

PMID- 16889116
TI  - Theories of therapeutic evolution for juvenile drug courts in the face of the
      onset of the co-occurrence of mental health issues and substance/alcohol abuse.

PMID- 16889118
TI  - Design, synthesis and diuretic activity of some novel 2,4-diamino-6-aryl-7
      arylaminopyrimido [4,5-d]pyrimidin-5(6H)-ones.
AB  - Synthesis and diuretic activity of some novel 2,4-diamino-6-aryl-7
      arylaminopyrimidol4,5-d]pyrimidin-5(6H) -ones were described. The series was
      designed on the basis of structural similarity between pteridines and
      pyridopyrimidines. Designed molecules were synthesized by cyclo-condensation of 5
      cyano-6-methylmercapto-3-aryl-2-arylaminopyrimidin-4(3H)-one with guanidine. All
      the compounds were screened for their diuretic activity using triamterene and
      furosemide as standard drugs. Compounds 2a, 2b, 2d, 2e and 2f were found more
      potent than triamterene. Compound 2e exhibited diuretic activity comparable to
      furosemide with greater natriuretic effect. It also exhibited significant
      antihypertensive activity.

PMID- 16889117
TI  - Pharmacological and toxicological testing of the enantiomers of two chiral
      fomocaine alkylmorpholine derivatives in comparison to their in vitro
      interactions on drug metabolism in rats.
AB  - Between the stereoisomers of amide-type local anaesthetics differences have been
      noticed with respect to pharmacokinetics and side effects, but not regarding
      local anaesthetic capacity. Therefore, only S-(-)-ropivacaine has been introduced
      into clinical practice and with bupivacaine both the racemate and the S-(-)
      enantiomer (levobupivacaine) are available by now. Based on this background, the
      aim of the present study was to evaluate if there are also dissimilarities to be
      found both in the toxicity and in the effectiveness of the enantiomers of two
      newly synthesized chiral fomocaine alkylmorpholine derivatives, OW3 and OW13,
      with an additional C2-chain in 2- or an additional C3-chain in 3-position at the
      morpholine ring, respectively. For this purpose, in vitro the interaction
      capacity with cytochrome P450 (CYP)-mediated monooxygenase and oxidase functions
      was investigated using rat liver 9000 g supernatants or microsomes. In vivo LD50,
      paresis of the N. ischiadicus and surface and conduction anaesthesia (cornea, N.
      ischiadicus) were tested in rats. The enantiomers of both OW3 and OW13 caused a
      concentration dependent inhibition of all CYP-mediated model reactions
      investigated. With all model reactions the (-)-enantiomer of OW3 was less
      effective than the (+)-form, whereas the opposite was the case with OW13. Also
      toxicity was lower with the (-)-enantiomer of OW3 and with the (+)-form of OW13
      than with the respective counterparts. With both derivatives no clear-cut
      dissimilarities were noticed in the local anaesthetic capacity of the
      enantiomers. None of the four compounds caused paresis. Thus, similar to amide
      type local anaesthetics, also with the enantiomers of chiral fomocaine
      alkylmorpholine derivatives differences in pharmacokinetic properties and
      toxicity could be demonstrated.

PMID- 16889119
TI  - HPLC determination of omeprazole in human plasma using a monolithic column.
AB  - A rapid and sensitive HPLC method using a monolithic column has been developed
      for quantification of omeprazole (CAS 73590-58-6) in plasma. The method was
      specific and sensitive with a quantification limit of 10 ng/ml. Sample
      preparation involves simple, one-step extraction procedure and analytical
      recovery was complete. The separation was carried out in reversed-phase
      conditions using a Chromolith Performance (RP-18e, 100 x 4.6 mm) column with an
      isocratic mobile phase consisting of 0.01 mol/l disodium hydrogen phosphate
      buffer-acetonitrile (73:27 v/v) adjusted to pH 7.1. The wavelength was set at 302
      nm. The calibration curve was linear over the concentration range 20-1500 ng x
      ml(-1). The coefficients of variation for inter-day and intra-day assay were
      found to be less than 7%.

PMID- 16889120
TI  - Double-blind, randomized evaluation of clinical efficacy and tolerability of an
      apple pectin-chamomile extract in children with unspecific diarrhea.
AB  - BACKGROUND: Acute diarrhea is one of the most common childhood diseases. The main
      aim of therapy is oral rehydration, mostly using a glucose-electrolyte solution.
      Results from a previous study (DIALOG I) investigating adjuvant treatment with a
      medicinal preparation containing an apple pectin-chamomile extract (Diarrhoesan)
      indicated a significantly reduced duration of diarrhea in children. OBJECTIVES:
      The objective of the present clinical placebo-controlled, double-blind study
      (DIALOG II) was to assess the clinical efficacy and tolerability of the apple
      pectin-chamomile extract on a larger number of patients. METHODS: The
      investigation was designed as a multicenter, randomized, double-blind, placebo
      controlled parallel study enrolling 255 patients presenting with acute diarrhea.
      Patients were aged between 6 months and 6 years and treated on an outpatient
      basis with either an apple pectin-chamomile preparation or placebo. As a basic
      medication, each child received a glucose-electrolyte solution on the first day
      of treatment. RESULTS: The primary outcome (primary efficacy parameter) included
      a combined analysis of stool frequency, stool The statistical analysis revealed a
      superior efficacy of the tested preparation over placebo with a significantly
      reduced stool frequency in the treatment group compared to the control group. The
      results were corroborated by efficacy assessment performed by investigators and
      patients. Treatment was well tolerated, with an incidence of adverse effects
      similar to placebo. CONCLUSION: These findings support the concept of a
      beneficial influence of the investigated vegetable extract in shortening the
      course of the disease and relieving associated symptoms.

PMID- 16889121
TI  - Structure-activity relationship study of androstene steroids with respect to
      local anti-inflammatory activity.
AB  - A sex hormone, 3beta-acetoxy-17beta-hydroxy-androst-5-ene (1) (CAS 1639-43-6),
      was isolated from aerial parts of Acacia nilotica. This compound is reported to
      have anti-inflammatory activity. In view of this, considering this molecule as a
      lead molecule different androstene compounds were synthesized to study their
      potency and structure-activity relationship with respect to local anti
      inflammatory activity. The experiments indicated that 17 ketonic compounds were
      more active towards inflammation than their oxime analogues. Similarly, for the
      compounds containing an acetyl group fixed at C-3 position a decreasing trend of
      activity was observed in the order of ketonic, hydroxyl, oxime and acetyl group,
      respectively, when these groups are at C-17 position.

PMID- 16889122
TI  - Clinical activity of folinic acid in patients with chronic fatigue syndrome.
AB  - A high incidence of severe B-cell immunodeficiency and chronic reactivated
      Epstein-Barr virus (EBV) infection in patients with chronic fatigue syndrome
      (CFS) is reported herein. Of the 58 patients evaluated, 100% had evidence of
      prior EBV exposure and 72% had evidence for reactivated EBV infection. Notably,
      94% of CFS patients had B-cell immunodeficiency with a marked depletion of their
      CD19+IgM+ mature B-lymphocyte population. A remarkable 81% of CFS patients
      experienced subjective improvement of their symptoms after treatment with folinic
      acid (CAS 58-05-9, leucovorin). The findings provide unprecedented evidence that
      CFS frequently is a folinic acid responsive clinical entity accompanied by B-cell
      immunodeficiency and inappropriate antibody responses to EBV.

PMID- 16889123
TI  - Novel antitumor and radioprotective sulfonamides containing pyrrolo [2,3
      d]pyrimidines.
AB  - Several sulfonamides having pyrrole (5a-c, 8, 11b-19, 23, 24), pyrrolo[2,3-d]
      pyrimidine (6, 7, 10, 20, 21, 25) and pyrrolo[2,3-b]pyridine (22) were
      synthesized and evaluated for their antitumor and radioprotective activities. The
      structure of the synthesized compounds was elucidated by elemental analyses and
      spectral data. Compounds 5a, 16, 17, 19, and 23 displayed more potent antitumor
      activities than the reference drug, doxorubicin. On the other hand compounds 19,
      23 and 25 exhibited radioprotective activities.

PMID- 16889125
TI  - Unmarried cohabitation and union stability: testing the role of diffusion using
      data from 16 European countries.
AB  - Cohabitors and married people who cohabited before marriage have higher risks of
      union dissolution than people who married without prior cohabitation. However,
      these differences in union stability vary markedly between countries. We
      hypothesize that the impact of cohabitation on union stability depends on how far
      cohabitation has diffused within a society. We test this hypothesis with data
      from 16 European countries. The results support our hypothesis: former cohabitors
      run a higher risk of union dissolution than people who married without prior
      cohabitation only in societies in which cohabitation is a small minority or a
      large majority phenomenon.

PMID- 16889124
TI  - Reliability of the cloned-enzyme donor immunoassay (CEDIA) for cocaine in human
      serum in the range between the detection limit and the cut-off.
AB  - Immunoassays are used worldwide for the rapid screening of drugs. Despite the
      fact that they are highly valuable tools for the testing of legal and illicit
      drugs, there is a non-negligable risk of false-positive and false-negative
      findings and many pitfalls must be taken into account when using these tests in
      an uncritical manner and without valid confirmation procedures. In order to check
      the correlation between cloned-enzyme donor immunoassay (CEDIA) readings and
      exact determined gas chromatography/mass spectrometry (GC/MS) values for
      benzoylecgonine, a total of 472 serum samples was measured with an immunoassay
      (CEDIA) as well as GC/MS. As a result, it was shown that in the lower area of
      concentration, up to approx. 300 ng equ. benzoylecgonine/ml, there is a
      semiquantitative useful correlation. With higher concentrations, the values shift
      more and more apart and many runaways are visible. Generally the use of tests for
      materials other than those declared is excluded from the manufacturer's warranty
      and is at the user's own risk, but the authors found that many immunochemical
      tests with a certification only for the use in urine are well suited to the
      screening of serum samples, and even low readings could be confirmed by GC/MS.
      With blood or serum as sample, it could be regularly observed that generally very
      small readings could not only be confirmed with mass spectrometry but could in
      most cases also be quantified. This was the key factor in determining the rate of
      confirmation in 495 cases. In total, an incredibly high reliability for the CEDIA
      cocaine test (via benzoylecgonine) was shown up to the area of detection
      (detection limit), far below the cut-off. These results confirm the extraordinary
      sensitivity and specificity of this test also for blood or serum as sample
      material to be tested.

PMID- 16889127
TI  - The rising share of nonmarital births: fertility choice or marriage behavior?
AB  - Much of the sharp rise in the share of nonmarital births in the United States has
      been attributed to changes in the fertility choices of unmarried and married
      women-in response, it is often argued, to public policy. In contrast, we develop
      and test a model that attributes the rise to changes in marriage behavior, with
      no necessary changes infertility. A variety of empirical tests strongly support
      this conclusion and invites focused attention to issues related to marriage
      behavior as well as to the interactions between marriage and fertility.

PMID- 16889126
TI  - Marriage or dissolution? Union transitions among poor cohabiting women.
AB  - The objective of this paper is to identify the incentives and barriers to
      marriage among cohabiting women, especially disadvantaged mothers who are targets
      of welfare reform. We use the newly released cohabitation data from the National
      Longitudinal Survey of Youth (1979-2000), which tracks the partners of cohabiting
      women across survey waves. Our results support several conclusions. First,
      cohabiting unions are short-lived--about one-half end within one year, and over
      90% end by the fifth year. Unlike most previous research, our results show that
      most cohabiting unions end by dissolution of the relationship rather than by
      marriage. Second, transitions to marriage are especially unlikely among poor
      women; less than one-third marry within five years. Cohabitation among poor women
      is more likely than that among nonpoor women to be a long-term alternative or
      substitute for traditional marriage. Third, our multinomial analysis of
      transitions from cohabitation into marriage or dissolution highlights the
      salience of economically disadvantaged family backgrounds, cohabitation and
      fertility histories, women's economic resources, and partner characteristics.
      These results are interpreted in a policy environment that increasingly views
      marriage as an economic panacea for low-income women and their children.

PMID- 16889128
TI  - Gendering family composition: sex preferences for children and childbearing
      behavior in the Nordic countries.
AB  - It has been argued that a society's gender system may influence parents' sex
      preferences for children. If this is true, one should expect to find no evidence
      of such preferences in countries with a high level of gender equality. In this
      article, we exploit data from population registers from Denmark, Finland, Norway,
      and Sweden to examine continuities and changes in parental sex preferences in the
      Nordic countries during the past three to four decades. First, we do not observe
      an effect of the sex of the first born child on second-birth risks. Second, we
      detect a distinct preference for at least one child of each sex among parents of
      two children. For third births, Danish, Norwegian, and Swedish parents seem to
      develop a preference for having a daughter, while Finns exhibit a significant
      preference for having a son. These findings show that modernization and more
      equal opportunities for women and men do not necessarily lead to parental gender
      indifference. On the contrary, they may even result in new sex preferences.

PMID- 16889129
TI  - Sex preferences and fertility in South Korea during the year of the Horse.
AB  - Since antiquity, people in several East Asian countries, such as China, Japan,
      and South Korea, have believed that a person is destined to possess specific
      characteristics according to the sign of the zodiac under which he or she was
      born. South Koreans, in particular, have traditionally considered that the year
      of the Horse bears inauspicious implications for the birth of daughters. Using
      monthly longitudinal data at the region level in South Korea between 1970 and
      2003, we found that in the year of the Horse, the sex ratio at birth
      significantly increased while fertility decreased.

PMID- 16889130
TI  - Reproductive health and domestic violence: are the poorest women uniquely
      disadvantaged?
AB  - We use Demographic and Health Survey data from Cambodia, the Dominican Republic,
      and Haiti to compare women in different poverty and violence categories in terms
      of their experience of selected reproductive health outcomes. "Poor" women are
      those who belong to the bottom quintile of households arrayed according to a
      widely accepted asset-based wealth index. The results suggest that women who are
      both poor and have experienced violence are not unique in their reproductive
      health disadvantage. In particular, for all three reproductive health outcomes we
      consider the negative association with having experienced violence cuts across
      all women, poor and wealthy.

PMID- 16889131
TI  - The foster care crisis: what caused caseloads to grow?
AB  - Foster care caseloads more than doubled from 1985 to 2000. This article provides
      the first comprehensive study of this growth by relating state-level foster care
      caseloads to state-specific characteristics and policies. We present evidence
      that increases in female incarcerations and reductions in cash welfare benefits
      played dominant roles in explaining the growth in foster care caseloads over this
      period. Our results highlight the need for child welfare policies designed
      specifically for the children of incarcerated parents and parents who are facing
      less generous welfare programs.

PMID- 16889132
TI  - Unhealthy assimilation: why do immigrants converge to American health status
      levels?
AB  - It is well documented that immigrants are in better health upon arrival in the
      United States than their American counterparts but that this health advantage
      erodes over time. We study the potential determinants of this "healthy immigrant
      effect, " with a particular focus on the tendency of immigrants to converge to
      unhealthy American BMI levels. Using data from the National Health Interview
      Survey, we find that average female and male immigrants enter the United States
      with BMIs that are approximately two and five percentage points lower than native
      born women and men, respectively. Consistent with the declining health status of
      immigrants the longer they remain in the United States, we also find that female
      immigrants almost completely converge to American BMIs within 10 years of
      arrival, and men close a third of the gap within 15 years.

PMID- 16889133
TI  - Foreign-born emigration: a new approach and estimates based on matched CPS files.
AB  - The utility of postcensal population estimates depends on the adequate
      measurement of four major components of demographic change: fertility, mortality,
      immigration, and emigration. Of the four components, emigration, especially of
      the foreign-born, has proved the most difficult to gauge. Without "direct"
      methods (i.e., methods identifying who emigrates and when), demographers have
      relied on indirect approaches, such as residual methods. Residual estimates,
      however are sensitive to inaccuracies in their constituent parts and are
      particularly ill-suited for measuring the emigration of recent arrivals. Here we
      introduce a new method for estimating foreign-born emigration that takes
      advantage of the sample design of the Current Population Survey (CPS): repeated
      interviews of persons in the same housing units over a period of 16 months.
      Individuals appearing in a first March Supplement to the CPS but not the next
      include those who died in the intervening year, those who moved within the
      country, and those who emigrated. We use statistical methods to estimate the
      proportion of emigrants among those not present in the follow-up interview. Our
      method produces emigration estimates that are comparable to those from residual
      methods in the case of longer-term residents (immigrants who arrived more than 10
      years ago), but yields higher--and what appear to be more accurate--estimates for
      recent arrivals. Although somewhat constrained by sample size, we also generate
      estimates by age, sex, region of birth, and duration of residence in the United
      States.

PMID- 16889134
TI  - Reassessing racial and socioeconomic disparities in environmental justice
      research.
AB  - The number of studies examining racial and socioeconomic disparities in the
      geographic distribution of environmental hazards and locally unwanted land uses
      has grown considerably over the past decade. Most studies have found
      statistically significant racial and socioeconomic disparities associated with
      hazardous sites. However there is considerable variation in the magnitude of
      racial and socioeconomic disparities found; indeed, some studies have found none.
      Uncertainties also exist about the underlying causes of the disparities. Many of
      these uncertainties can be attributed to the failure of the most widely used
      method for assessing environmental disparities to adequately account for
      proximity between the hazard under investigation and nearby residential
      populations. In this article, we identify the reasons for and consequences of
      this failure and demonstrate ways of overcoming these shortcomings by using
      alternate, distance-based methods. Through the application of such methods, we
      show how assessments about the magnitude and causes of racial and socioeconomic
      disparities in the distribution of hazardous sites are changed. In addition to
      research on environmental inequality, we discuss how distance-based methods can
      be usefully applied to other areas of demographic research that explore the
      effects of neighborhood context on a range of social outcomes.

PMID- 16889135
TI  - Pathogenesis of progressive adolescent idiopathic scoliosis. Platelet activation
      and vascular biology in immature vertebrae: an alternative molecular hypothesis.
AB  - Altered paraspinal muscle activity was suggested by Lowe et al (2002) to explain
      a relationship between Cobb angle changes and platelet calmodulin level changes
      in adolescent idiopathic scoliosis (AIS). We formulate an alternative platelet
      skeletal hypothesis which involves: (1) a small scoliosis curve; (2) axial loads
      transmitted directly from the intervertebral discs to vertebral body growth
      plates (endplate physes) as axial inward bulges that create mechanical micro
      insults; (3) the latter cause dilatation of juxta-physeal vessels and, in
      deforming vertebrae, vascular damage with exposure of subendothelial collagen and
      other agonist proteins; (4) subject to predisposition, platelet activation with
      calmodulin changes occurs within dilated vessels of deforming vertebral bodies;
      (5) the activated platelets in juxta-physeal vessels release growth factors that,
      after extravasation, abet the hormone-driven growth of the already mechanically
      compromised vertebral endplate physes to promote the relative anterior spinal
      overgrowth and curve progression of AIS. The hypothesis links several fields in
      each of which research within ethical restraints is suggested to refute it.

PMID- 16889136
TI  - Massive osteolysis (Gorham's disease) affecting the femur.
AB  - Gorham's massive osteolysis is one of the five classical types of idiopathic
      osteolysis. The femoral localisation is rare. The diagnosis is based on
      anamnestic data (non-hereditary), on biochemical data (absence of nephropathy),
      on radiographical data (progressive monocentric osteolysis without periosteal
      reaction), and on histological data (intraosseous angiomatosis with either
      capillaries or lymph vessels, or both; eventually fibrosis). Nowadays, treatment
      mostly consists of amputation or arthroplasty, combined with radiotherapy.
      Spontaneous arrest of the disease occasionally occurs, but this is unpredictable.
      The possible role of gene-therapy in the regulation of osteoclastic activity has
      to be determined in the future. Review of the literature produced 22 cases of
      Gorham's massive osteolysis with a localisation at the femur massive osteolysis,
      including one personal case.

PMID- 16889137
TI  - Elastic stable intramedullary nailing for midclavicular fractures in athletes:
      indications, technical pitfalls and early results.
AB  - This prospective consecutive case series was done to evaluate indications,
      technical pitfalls and functional outcome of elastic stable intramedullary
      nailing of displaced midclavicular fractures in 14 athletes. Constant score and
      radiographs were evaluated after 1 and 6 weeks, 3 months and 6 months in 13
      patients. Mean age was 28 years. The average follow-up was 17 months. Mean
      operation time was 62 minutes. Open reduction through an additional small
      incision was necessary for 7 fractures. Mean hospital stay was 1.2 days.
      Secondary fracture displacement was observed in 1 patient. The Constant score
      averaged 81 after 1 week, 96 after 6 weeks and 98 after 6 months. Compared to the
      contralateral side, average shortening of the clavicle was 1.7 mm. Overall,
      elastic stable intramedullary nailing provided good restoration of the length of
      the clavicle and allowed immediate active mobilisation with early return to
      normal activity. Functional results were excellent.

PMID- 16889138
TI  - Calcifying tendinitis of the rotator cuff: functional outcome after arthroscopic
      treatment.
AB  - In this study, we assessed the functional results after arthroscopic excision of
      rotator cuff calcifications. Sixty-one shoulders in 57 patients with chronic
      calcifying tendinitis of the rotator cuff were treated with arthroscopic
      excision, subacromial bursa debridement and shaving. In patients with fraying or
      roughness of the coracoacromial ligament, an acromioplasty was also performed.
      Patients were evaluated after a mean follow-up of 15 months. The modified
      Constant score and DASH score significantly improved from 33.4 to 66.8 and from
      49.7 to 17.3 respectively. Performing an acromioplasty did not influence the
      final outcome. Frozen shoulder was a frequent complication (18%) without
      significant effect on the final DASH or Constant score. The presence of residual
      calcifications after arthroscopic needling did not influence the final outcome.
      We therefore believe that the presence of residual calcifications can be accepted
      if this is deemed necessary to preserve the integrity of the tendon.

PMID- 16889139
TI  - Clinical and radiological presentation of tuberculosis of the elbow.
AB  - The diagnosis of tuberculosis of the elbow is often missed in the early stages,
      so that irreversible osteoarticular destruction may occur. The authors describe
      their experience with 48 elbows in 47 patients. Most patients were in the first
      three decades of life. All patients presented with pain, swelling and loss of
      motion. Sixteen elbows had discharging sinuses. Eight elbows had a palpable
      supratrochlear lymph node. Six were completely ankylosed in flexion, at an angle
      of 73.3 degrees on average; the other elbows had a mean range of motion from 31.3
      degrees to 105.2 degrees. Plain radiographs showed periosteal reaction in 6
      elbows without discharging sinus and thus free of superinfection, and para
      articular round to oval lytic lesions in 29. According to the radiological
      classification of Martini, 6 elbows were in stage 1, 13 in stage 2, 20 in stage 3
      and 9 in stage 4. All the patients were treated conservatively with
      antituberculous drugs for a minimum period of 9 months. Twenty-seven elbows were
      available for follow-up, with a minimum follow-up period of 9 months. The
      functional results were related to the radiological stage at presentation, not to
      the duration of symptoms or to the initial loss of range of motion.

PMID- 16889140
TI  - Outcome of open versus endoscopic approach for the surgical treatment of carpal
      tunnel syndrome.
AB  - The authors retrospectively evaluated two comparable groups of patients who
      underwent either open (103 patients) or endoscopic decompression (86 patients) of
      the carpal tunnel with the two portal technique. There were 95 patients available
      for follow-up in the open group and 79 in the endoscopic group. The average
      follow-up period was 38 months (range: 12 to 60). Each patient received a
      questionnaire in order to determine if there was any difference in severity of
      symptoms and functional status, patient satisfaction and time to return to
      activities of daily living. The questionnaire also focused on complications and
      on readiness to undergo the same operation again. There was no significant
      difference between the two techniques in any of the outcome measurements.

PMID- 16889141
TI  - Poor outcome following bilateral sacroiliac joint fusion for degenerative
      sacroiliac joint syndrome.
AB  - The purpose of this retrospective study was to evaluate the clinical and
      radiological outcome of bilateral sacroiliac joint (SIJ) fusion, using a new
      technique, in patients with a chronic SIJ syndrome. Seventeen patients with
      chronic low back pain, with a positive response to specific diagnostic tests for
      the SIJ, were considered candidates for bilateral sacroiliac fusion. The surgical
      indication was based on the results of local anaesthetic joint infiltration,
      temporary external fixation or bone scan. Ten patients had had previous surgery
      on the lumbar spine. Bilateral posterior SIJ fusion was performed with internal
      fixation and decortication of the sacroiliac joint, using a separate approach to
      each joint. Local bone grafting was performed. At the time of follow-up (on
      average 39 months after surgery), 3 patients reported moderate or absent pain, 8
      marked pain and 6 severe pain. Seven patients showed a symptomatic non-union;
      union occurred in only 6 cases. Eighteen percent of the patients were satisfied,
      but in the other 82% the results were not acceptable. Reoperation was performed
      in 65% of the patients. Our results with bilateral posterior SIJ fusion were
      disappointing, which may be related with difficulties in patient selection, as
      well as with surgical technique. Better diagnostic procedures and possibly other
      surgical techniques might provide more predictable results, but this remains to
      be demonstrated.

PMID- 16889142
TI  - Epiphysiodesis of the greater trochanter in Legg-Calve-Perthes disease: The
      importance of timing.
AB  - Patients with Legg-Calve-Perthes disease (LCP) often exhibit relative overgrowth
      of the greater trochanter and shortening of the femoral neck. Biomechanically,
      this corresponds to a shorter lever arm and a decreased muscle tension which may
      result in a Trendelenburg gait and pelvic instability. This is a retrospective
      study of 31 patients (32 hips) with LCP disease and relative overgrowth of the
      greater trochanter who were treated with an epiphyseodesis. The average age at
      operation was 10 years and 6 months. We evaluated the patients clinically with
      the Trendelenburg sign and analysed on radiographs the growth of the greater
      trochanter and the neck-shaft angle of the normal hip and the pre- and
      postoperative growth and angle of the involved hip. We did not find any
      significant differences between the pre- and postoperative values. After a mean
      follow-up of 4 years and 2 months, however, 27 patients presented with a negative
      Trendelenburg sign (versus 14 patients preoperatively).

PMID- 16889143
TI  - The percutaneous compression plate (PCCP) in the treatment of trochanteric hip
      fractures in elderly patients.
AB  - We carried out a prospective study to assess the value of mini-invasive
      osteosynthesis with the PerCutaneous Compression Plate (PCCP) in the treatment of
      trochanteric hip fractures in elderly patients. Sixty five consecutive patients
      were included, with an average age at surgery of 84.2 years (range : 63 to 99),
      with more than 93% ASA 2, 3 or 4 patients. No perioperative complications were
      noted. All but two patients were ambulatory with weight bearing two days after
      operation. The postoperative blood transfusion rate was only 25%. No patient was
      lost to follow-up. We noted 11 deaths (17%) at the end of follow-up (5 during
      hospitalisation and 6 during the first 9 months). The re-operation rate was 4.5%.
      Osteosynthesis with the PCCP allows for decreased intraoperative bleeding and
      minimises injury to muscle and tendon structures. The stability and quality of
      the construct enable early recovery of patients while limiting morbidity for this
      type of fracture.

PMID- 16889144
TI  - Clinical and radiological outcome following total hip arthroplasty with an
      uncemented trabecular metal monoblock acetabular cup.
AB  - Uncemented acetabular components are associated with a significant incidence of
      polyethylene wear and secondary osteolysis. The new tantalum/polyethylene
      composite (Hedrocel) acetabular component is designed to reduce the polyethylene
      wear and to increase the longevity of the acetabular cups. We report our short-
      term clinical outcome and patient satisfaction following use of an uncemented
      tantalum acetabular component in a single centre. During 1999 to 2002, 113
      uncemented tantalum acetabular cups were implanted in 105 patients in our
      institution. The average age at operation was 56.8 years. All patients were
      assessed pre- and post-operatively with the Oxford 12 item hip questionnaire and
      standard radiographs of the pelvis. At a mean follow-up of 32 months (range: 18
      to 48), 112 Hedrocel cups were assessed in 104 patients. Subjective patient's
      satisfaction was also assessed. At the time of evaluation, one patient had died
      due to an unrelated cause. Eight patients had bilateral acetabular cups
      implanted. The mean Oxford hip score improved from 45 preoperatively to 14 post
      operatively. Subjectively 99% were very satisfied or satisfied. Only one patient
      expressed dissatisfaction about the outcome of this surgery. Radiologically,
      there were no signs of cup loosening or wear. This study shows that at short-term
      the new uncemented tantalum/polyethylene composite (Hedrocel) acetabular
      component can yield a satisfactory clinical and radiological outcome and has a
      high patient satisfaction. Although the short-term result from our centre is very
      encouraging, similar results from other centres and longer follow-up are
      required.

PMID- 16889145
TI  - Hedrocel trabecular metal monoblock acetabular cups: mid-term results.
AB  - The most important factors for long-term survival of cementless prostheses are
      the initial fixation, the osteoconducting properties of the metal shell and the
      bony response. Porous tantalum, a new biomaterial with a geometric structure
      similar to trabecular bone, was reported in animal studies to allow for bone
      ingrowth even when 3-mm gaps exist between the implant and the bone. This new
      material may improve the durability and stability of hip arthroplasties. We
      analysed the behaviour of the underlying acetabular bone, based on radiographs
      taken 46 months or longer after implantation of monoblock cementless acetabular
      cups made of porous tantalum. Clinical evaluation was done by means of the Harris
      Hip Score. The acetabular ARA-score, ranging from poor to excellent, was
      excellent in 80 % of the cases, 46 months or longer after implantation. The
      clinical condition of the patients as assessed with the Harris Hip Score was
      excellent for 65 % of the patients.

PMID- 16889146
TI  - Treatment of Gustilo grade III B supracondylar fractures of the femur with
      Ilizarov external fixation.
AB  - Twenty patients who had been treated with Ilizarov external fixation for a
      Gustilo grade IIIB supracondylar fracture of the femur were functionally assessed
      12 to 52 months after treatment. Fourteen fractures were type C3 and 6 were type
      C2 according to the AO classification. Fractures were united at an average of 39
      +/- 9 weeks. There was a final knee extension deficit of 5 degrees to 10 degrees
      (12.2 degrees +/- 3.5 degrees) and flexion reached 110 degrees +/- 10 degrees in
      type C2 and 73 degrees +/- 36 degrees in C3 supracondylar fractures. Forty
      percent of the supracondylar fractures had 4cm shortening and 40% had 1.5 cm. Pin
      track infection occurred in 21%. Half of the C3 fracture cases had problems with
      pain on walking, needed support and had pain at rest, whereas no patients had
      difficulty getting out of a chair, going up and down stairs. However, all C2 type
      fractures had problems with all types of function.

PMID- 16889147
TI  - Tuberculous spondylitis: abscess drainage after failure of anti-tuberculous
      therapy.
AB  - Spinal tuberculous abscesses usually respond to anti-tuberculous drugs. The
      purpose of this study was to evaluate the results of surgical drainage after
      failure of first-line anti-tuberculous drugs. Patients with spinal instability or
      vertebral collapse were excluded from the study. The authors retrospectively
      reviewed 11 patients. The operation was successful in all patients.
      Anterior/posterior spinal fusion or curettage was not performed. Drains were
      removed after two to three days. None of the patients required a second
      operation. Complications, such as spinal instability, vertebral collapse, or
      death did not occur.

PMID- 16889148
TI  - Prospective assessment of cervical fusion status: plain radiographs versus CT
      scan.
AB  - The purpose of this prospective study was to compare the pseudarthrosis rate
      after anterior cervical fusion, estimated either with static and dynamic plain
      radiographs or with two-dimensional CT-scans. There is a plethora of radiographic
      tools and criteria used to determine pseudarthrosis after cervical spine fusion.
      However, it is not known to which extent these tools correlate with each other.
      Forty-seven adult patients were enrolled in this study, about one year after
      surgery. Four independent blinded observers evaluated the roentgenological data.
      CT assessment led to higher pseudarthrosis rates than plain radiographs: 13 to
      31% according to CT; 2 to 16% according to plain radiographs. The difference
      averaged 11%. Consistency between reviewers was higher with CT (average
      agreement: 89%; range 82%-96%) than with plain radiographs (average agreement:
      81%; range: 76% to 87%). The need to accurately document pseudarthrosis is
      critical as it helps direct the postoperative management of the patient. The
      present study stresses the value of computed tomography. However, surgical
      exploration continues to be the gold standard.

PMID- 16889149
TI  - Posterior endoscopic discectomy for the treatment of lumbar disc herniation.
AB  - The procedure of posterior endoscopic discectomy (PED) is an attempt to allow for
      a standard familiar microsurgical discectomy to be performed using standard
      microsurgical techniques via a minimally invasive approach. The aim of this study
      was to evaluate our results with PED for lumbar disc herniation and to assess the
      advantages, disadvantages and clinical outcomes of the technique. Between
      February 2002 and August 2004, 71 patients with a mean age of 44 years (range :
      24 to 73) underwent PED. The operated disc levels were L5-S1 in 37 patients, L4
      L5 in 26 patients and L3-L4 in 8 patients. Mean operative time was 84 min. (41
      135 min.). All patients experienced substantial relief of their leg pain
      immediately after the operation, mobilised very early after recovery from the
      anaesthesia and were discharged home within 24 hours of surgery with only oral
      NSAID +/- myorelaxants. PED has advantages like better illumination, better
      magnification, and better visualisation through the rotation of the 25 degrees
      lens, minimal bone resection and minimal epidural fibrosis, less postoperative
      pain, better cosmesis, shorter hospitalisation, early mobilisation and shorter
      recovery. On the other hand, PED has a longer learning curve than open
      discectomy, the operative time is usually longer than with open procedures and
      bidimensional vision may cause loss of depth sensation, and it entails a longer
      anaesthesia time due to the preparation period of the system.

PMID- 16889150
TI  - Stabilisation of a posteriorly unstable glenohumeral joint during total shoulder
      arthroplasty: A novel capsulorrhaphy technique.
AB  - Restoration of the soft tissue balance is of great importance during shoulder
      arthroplasty. We report a novel technique of posterior capsulorrhaphy through an
      anterior approach for the management of intraoperative posterior instability
      during implantation of the prosthesis. After the operation, the patients were
      able to follow a rehabilitation program with some minor restrictions, avoiding
      the necessity of a shoulder spica or other constrictive measures. This technique
      is simple, safe and sufficient to address instability due to abundance of the
      posterior shoulder capsule.

PMID- 16889151
TI  - Congenital pseudarthrosis of the clavicle: the role of CT-scanning.
AB  - Congenital pseudarthrosis of the clavicle is a rare entity. It presents on the
      right side in 90% of the patients, and bilaterally in up to 10%. The authors
      report the case of a 4-year-old boy who presented with a painful deformity over
      his right mid-clavicular area. Plain radiographs were inconclusive, although the
      opposite is true in most cases. A computed tomography (CT) 3-D reconstruction
      showed a pseudarthrosis of the clavicle, and excluded a neoplastic, infective or
      traumatic origin. Treatment involved excision of the pseudarthrosis, internal
      fixation with a contoured reconstruction locking plate, and bone grafting. The
      authors prefer operative treatment, but this is not universally accepted.

PMID- 16889152
TI  - Paediatric transverse divergent dislocation of the elbow.
AB  - Paediatric elbow dislocations are uncommon injuries, accounting for 3-6% of all
      elbow injuries in childhood. A divergent elbow dislocation is an even more
      infrequent injury, where in addition to the elbow dislocation there is divergence
      of the proximal radius and ulna, either in a transverse (extremely rare) or in an
      anteroposterior plane, as a result of the distal humerus being forced between the
      proximal ends of the forearm bones. The lesion results from indirect forces
      transmitted to the elbow from a fall on the outstretched hand. The authors report
      a case of transverse divergent elbow dislocation in an 8-year-old boy, treated by
      closed reduction and immobilisation in a cast. At 6 months follow-up the patient
      had regained a full range of motion, without instability or pain.

PMID- 16889153
TI  - Bicipitoradial bursitis. A case report.
AB  - Mass lesions in the antecubital fossa are uncommon and therefore unknown. We
      report a case of bicipitoradial bursitis, which initially was mistaken for a
      malignant lesion.

PMID- 16889154
TI  - Diphtheroid infection of a total knee arthroplasty following femoral percutaneous
      transluminal coronary angioplasty.
AB  - A 61-year-old male had a successful left total knee arthroplasty but one year
      later developed a deep diphtheroides infection of the joint following femoral
      percutaneous transluminal coronary angioplasty without antimicrobial prophylaxis.
      Diphtheroides is an uncommon organism to infect a joint replacement and it has
      not been reported in the medical literature previously to our knowledge. There is
      little evidence to support the routine use of prophylactic antibiotics to cover
      percutaneous transluminal coronary angioplasty in the general population;
      however, we would encourage its use, and the use of an alternative entry site
      (such as the radial artery) if a patient has a joint replacement in situ.

PMID- 16889155
TI  - Periprosthetic fracture of the tibial plateau after unicompartmental knee
      arthroplasty.
AB  - The authors report three cases of unicompartmental knee arthroplasty (UKA),
      complicated with peri-operative periprosthetic fracture of the tibial plateau.
      The surgical technique was held responsible in all cases. The initial treatment
      was different in every case; all patients ultimately underwent revision total
      knee arthroplasty with a good functional outcome. The authors emphasise the
      importance of careful preparation of the tibial plateau during UKA, adequate
      sizing of the tibial component and caution when using a hammer during
      implantation of the tibial component. When a tibial plateau fracture occurs, the
      treatment of choice should be immediate revision total knee arthroplasty.

PMID- 16889156
TI  - Atraumatic haemarthrosis following total knee replacement treated with selective
      embolisation.
AB  - Spontaneous haemarthrosis in the absence of anticoagulant medication or a
      bleeding disorder is a very rare complication after total knee arthroplasty. A
      case of recurrent spontaneous haemarthrosis following total knee replacement in a
      69-year-old patient is reported. Angiography was used to aid the diagnosis. It
      demonstrated an abnormal blush of vessels around the anterior aspect of the knee
      joint, that was fed by genicular branches and a recurrent branch of the anterior
      tibial artery. Selective embolisation of the bleeding vessels with coils led to
      immediate control of the bleeding. No further recurrence of haemarthrosis has
      been recorded.

PMID- 16889157
TI  - Publication bias in the pulmonary/allergy literature: effect of pharmaceutical
      company sponsorship.
AB  - BACKGROUND: A publication bias exists towards positive results in studies funded
      by pharmaceutical companies. OBJECTIVES: To determine whether drug studies in the
      pulmonary/allergy literature also demonstrate a publication bias towards more
      favorable results when a pharmaceutical company funds the study. METHODS: We
      reviewed all original articles published in seven pulmonary and allergy journals
      between October 2002 and September 2003. Included in the review were studies of
      inhaled corticosteroids (oral or nasal), long- or short-acting bronchodilators,
      or leukotriene receptor antagonists. Articles with funding from a pharmaceutical
      company and/or one or more authors employed by a pharmaceutical company were
      considered pharmaceutical company-sponsored studies. The remaining studies were
      considered not sponsored by a pharmaceutical company. Results were compared to
      ascertain whether positive results were obtained more frequently in the company
      sponsored studies. RESULTS: Of the 100 articles included in this review 63 were
      considered pharmaceutical company-sponsored research. Results favorable for the
      drugs studies were significantly more common in those funded by a pharmaceutical
      company (98% vs. 32%). CONCLUSIONS: In the pulmonary and allergy literature, as
      in other fields, there is a publication bias towards positive results in
      pharmaceutical company-sponsored research.

PMID- 16889158
TI  - Radiofrequency ablation of atrioventricular nodal reentry tachycardia: a 14 year
      experience with 901 patients at the Tel Aviv Sourasky Medical Center.
AB  - BACKGROUND: Atrioventricular nodal reentry tachycardia is the most frequent cause
      of regular, paroxysmal supraventricular tachycardia. Radiofrequency ablation of
      the slow pathway has been recommended as first-line therapy for curing AVNRT.
      OBJECTIVES: To report a 14 year experience of RFA of the slow pathway in patients
      with AVNRT treated in our laboratory. METHODS: A total of 901 consecutive
      patients (aged 9-92, mean 50.8 +/- 18.2 years) underwent RFA of the slow pathway.
      All patients had sustained AVNRT induced with or without intravenous
      administration of isoproterenol. A standard electrophysiologic method with three
      diagnostic and one ablation catheter was used in 317 patients (35.2%); in the
      remaining 584 patients (64.8%), only two electrode catheters (one diagnostic, one
      ablation) were used ("two-catheter approach"). RESULTS: Catheter ablation of the
      slow pathway abolished AVNRT induction in 877 patients (97.3%). In 14 patients
      (1.6%) the procedure was discontinued while in 10 (1.1%) the procedure failed. In
      864 patients (95.9%) there were no complications. Transient or permanent AV block
      occurred during the procedure in 31 patients (3.4%), of whom 8 (0.9%) eventually
      required pacemaker insertion (n = 7) or upgrade of a previously implanted WI
      pacemaker (n = 1) during the month following the procedure. The number of
      catheters used did not significantly affect the rate of results or complications
      of the ablation procedure. The success and complication rates remained stable
      over the years, although a significant trend for increased age and associated
      heart disease was observed during the study period. CONCLUSIONS: The results of
      this single-center large study, which included patients with a wide age range,
      showed results similar to those of previous studies. The use of a "two-catheter
      approach" (one diagnostic and one ablation) was as effective and safe as a multi
      catheter approach.

PMID- 16889159
TI  - Assessment of functional capacity in patients with chronic obstructive pulmonary
      disease: correlation between cardiopulmonary exercise, 6 minute walk and 15 step
      exercise oximetry test.
AB  - BACKGROUND: Different exercise tests are used to evaluate the functional capacity
      in chronic obstructive pulmonary disease. The cardiopulmonary exercise test is
      considered the gold standard, but the 6 minute walk and the 15 step exercise
      oximetry test are considerably less expensive. OBJECTIVES: To determine whether
      reliable data could be obtained at lower cost. METHODS: The study sample
      consisted of 50 patients with mild to severe stable COPD. All underwent pulmonary
      function test and the cardiopulmonary exercise test, 6 minute walk and 15 step
      exercise oximetry test as part of their regular follow-up visit. Functional
      capacity was graded according to each test separately and the functional
      capacities obtained were correlated. RESULTS: The results showed that most of the
      patients had severe COPD according to pulmonary function tests (mean forced
      expiratory volume in the first second 46.3 +/- 19.9% of predicted value). There
      was a good correlation between the cardiopulmonary exercise test and the 6 minute
      walk functional capacity classes (r = 0.44, P = 0.0013). We did not find such
      correlation between the 15 step exercise oximetry test and the cardiopulmonary
      exercise test (r = 0.07, P = 0.64). CONCLUSIONS: The study shows that the 6
      minute walk is a reliable and accurate test in the evaluation of functional
      capacity in COPD patients.

PMID- 16889161
TI  - Colchicine therapy and the cognitive status of elderly patients with familial
      Mediterranean fever.
AB  - BACKGROUND: [corrected] Colchicine is widely used for treating gout and familial
      Mediterranean fever. However, studies in animal models have reported ill effects
      of colchicine on the central nervous system, including cognitive function.
      OBJECTIVES: To evaluate the cognitive status of elderly FMF patients on long-term
      colchicine treatment. METHODS: The study group consisted of 55 FMF patients aged
      74 +/- 5, attending an FMF outpatient clinic and receiving colchicine treatment
      for 25.1 +/- 8.9 years. The Mini-Mental State Examination was used for cognitive
      evaluation. Patients' scores were compared with accepted age- and education
      adjusted cutoff scores, population-based norms, and scores of a matched control
      group of 56 subjects. RESULTS: Individually, all colchicine-treated FMF patients
      scored well above the age- and education-corrected cutoff scores. Overall, there
      was a large difference, 5.0 +/- 1.6, from the expected cutoff points, in favor of
      the study group scores (P < 0.001). The individual scores of the control group
      were also above the cutoff points, however with a lower but still statistically
      significant difference (3.71 +/- 1.15 points, P < 0.001). Compared to population
      based norms adjusted by age and education, the study group had significantly
      higher mean MMSE scores (27.2 +/- 2.2 vs. 25.5 +/- 2.4, P < 0.001). The control
      group's scores were also somewhat higher than expected, but not significantly so.
      CONCLUSIONS: Our results do not support the view that prolonged colchicine
      treatment may be associated with cognitive impairment. On the contrary, it is
      possible that long-term colchicine treatment may even confer protection against
      cognitive decline in patients with FMF.

PMID- 16889160
TI  - Adult calcific aortic stenosis and Chlamydia pneumoniae: the role of Chlamydia
      infection in valvular calcification.
AB  - BACKGROUND: Adult calcific aortic stenosis is a well-known clinical entity but
      its pathophysiology and cellular mechanism have yet to be defined. OBJECTIVES: To
      determine whether there is an association between the presence and severity of
      adult calcific aortic stenosis and Chlamydia pneumoniae seropositivity. METHODS:
      Forty adult patients (23 women, 17 men) were divided into three groups according
      to echocardiographic aortic valve area: Group A - 7 symptomatic subjects (age 67
      +/- 7 years) with normal aortic valve and normal coronary angiogram, Group B - 16
      patients (age 73 +/- 6) with moderate ACAS (AVA > 0.8 < or = 1.5 cm2), and Group
      C - 17 patients (age 76 +/- 7) with severe ACAS (AVA +/- 0.8 cm2). We tested for
      immunoglobulins M, G and A as retrospective evidence of C. pneumoniae infection
      using the micro-immunofluorescence method. Past C. pneumoniae infection was
      defined by IgG titer > 16 < or = 512. RESULTS: No patients in group A showed
      positive Ig for C. pneumoniae. IgM was not detected in any of the patients with
      ACAS (groups B and C) while 2 of 17 patients (12%) in group C showed IgA for the
      pathogen. High titers of IgG were found in 14 of 33 (42%) of the patients with
      moderate or severe ACAS: 5 of 16 (31%) in group B and 9 of 17 (53%) in group C (P
      = 0.2). Both groups had the same prevalence of coronary artery disease (66%). AVA
      was lower in IgG-seropositive patients than in the seronegative group (0.88 +/-
      0.3 cm2 vs. 1.22 +/- 0.4 cm2, respectively, P = 0.02). CONCLUSIONS: Past C.
      pneumoniae infection may be associated with a higher prevalence and greater
      severity of ACAS.

PMID- 16889162
TI  - Discharge of respiratory-compromised children after respiratory rehabilitation.
AB  - BACKGROUND: There is a growing demand for respiratory rehabilitation services for
      children dependent on tracheostomy and/or chronic mechanical ventilation.
      Discharging these patients home following their rehabilitation can be an arduous
      process. OBJECTIVES: To define the length of time required to rehabilitate and
      discharge these patients, and to identify predictors of a prolonged or failed
      discharge process. METHODS: We conducted a retrospective chart review of patients
      admitted to the Respiratory Rehabilitation Unit at Alyn Hospital, Jerusalem, over
      a 4 year period. RESULTS: Of the 48 patients identified, 31 (64.7%) were
      eventually discharged, 13 (27.1%) remained hospitalized long-term, and 4 (8.3%)
      died during their hospitalization. The median length of hospitalization was 10
      months: 6 months for purposes of rehabilitation therapy, and 4 months thereafter
      to resolve the logistics of discharge. Specific family characteristics--an
      unemployed father (odds ratio = 4.6, P = 0.02) and an additional family member
      with a disability (OR = 5.8, P = 0.03)--as well as ongoing mechanical ventilation
      at the time of discharge (OR = 5.5, P < 0.01) were found to positively correlate
      with a prolonged or failed discharge process. CONCLUSIONS: Hospitalization in a
      pediatric respiratory rehabilitation unit may be prolonged for both medical and
      non-medical reasons, with the process of discharge home being particularly
      difficult in certain subsets of patients. A proactive discharge policy by
      hospitals, improved community support services, and legislation defining the
      rights of home-ventilated children may facilitate more efficient discharge home
      of these patients.

PMID- 16889163
TI  - Neonatal transport of very low birth weight infants in Jerusalem, revisited.
AB  - BACKGROUND: Maternal transport, rather than neonatal transport, to tertiary care
      centers is generally advocated. Since a substantial number of premature
      deliveries still occur in hospitals with level I and level II nurseries, it is
      imperative to find means to improve their outcome. OBJECTIVES: To compare the
      neonatal outcome (survival, intraventricular hemorrhage and bronchopulmonary
      dysplasia) of inborn and outborn very low birth weight infants, accounting for
      sociodemographic, obstetric and perinatal variables, with reference to earlier
      published data. METHODS: We compared 129 premature infants with birth weights of
      750-1250 g delivered between 1996 and 2000 in a hospital providing neonatal
      intensive care to 99 premature babies delivered in a referring hospital. In the
      statistical analysis, variables with a statistical significant association with
      the outcome variables and dissimilar distribution in the two hospitals were
      identified and entered together with the hospital of birth as explanatory
      variables in a logistic regression. RESULTS: Accounting for the covariates, the
      odds ratios (outborns relative to inborns) were 0.31 (95% confidence interval =
      0.11-0.86, P = 0.03) for mortality, 1.37 (95% CI = 0.64-2.96, P = 0.42) for
      severe intraventricular hemorrhage, and 0.86 (95% CI = 0.38-1.97, P = 0.78) for
      bronchopulmonary dysplasia. The odds ratio for survival without severe
      intraventricular hemorrhage was 1.10 (95% CI = 0.55-2.20, P = 0.78). Comparing
      the current results with earlier (1990-94) published data from the same
      institution showed that mortality decreased in both the outborn and inborn
      infants (OR = 0.23, 95% CI = 0.09-0.58, P = 0.002 and 0.46; 95% CI = 0.20-1.04, P
      = 0.06, respectively), but no significant change in the incidence of severe
      intraventricular hemorrhage or brochopulmonary dysplasia was observed. Increased
      survival was observed also in these infants receiving surfactant, more so among
      the outborn. The latter finding could be attributed to the early, pre-transport
      surfactant administration, implemented only in the current study. CONCLUSIONS:
      Our data suggest that very low birth weight outborn infants may share an outcome
      comparable with that of inborn babies, if adequate perinatal care including
      surfactant administration is provided prior to transportation to a tertiary
      center.

PMID- 16889164
TI  - The Dead Sea, a unique natural health resort.

PMID- 16889165
TI  - Human herpesvirus-8: beyond Kaposi's .
AB  - Today, more than 10 years and 2000 articles since human herpesvirus 8 was first
      described by Chang et al., novel insights into the transmission and molecular
      biology of HHV-8 have unveiled a new spectrum of diseases attributed to the
      virus. The association of HHV-8 with proliferative disorders--including Kaposi's
      sarcoma, multicentric Castleman disease and primary effusion lymphoma--is well
      established. Other aspects of HHV-8 infection are currently the subject of
      accelerated research. Primary HHV-8 infection may manifest as a mononucleosis
      like syndrome in the immunocompetent host, or in various forms in the
      immunocompromised host. The association of HHV-8 with primary pulmonary
      hypertension was observed by Cool et al. in 2003, but six clinical trials
      evaluating the role of HHV-8 in pulmonary hypertension have not been able to
      replicate this intriguing observation. It has been speculated that HHV-8 may
      secondarily infect proliferating endothelium in patients with pulmonary
      hypertension. HHV-8 epidemiology, modes of transmission, new spectrum of disease
      and treatment are presented and discussed.

PMID- 16889166
TI  - The evidence behind our evidence-based decisions: cheques and balances.

PMID- 16889167
TI  - Radiofrequency catheter ablation of atrioventricular nodal reentrant tachycardia:
      does the number of catheters matter?

PMID- 16889168
TI  - Medicine is flourishing at the Dead Sea.

PMID- 16889169
TI  - Malignant mesothelioma: A disease that continues to mystify.

PMID- 16889170
TI  - Enteral feeding in terminal dementia--a dilemma without a consensual solution.

PMID- 16889171
TI  - Non-benefit of active nutritional support in advanced dementia.

PMID- 16889172
TI  - To feed or not to feed the terminal demented patient--is there any question?

PMID- 16889173
TI  - Familial Mediterranean fever and peritoneal malignant mesothelioma: a possible
      association?

PMID- 16889174
TI  - Benign cystic mesothelioma of the peritoneum.

PMID- 16889175
TI  - Behcet's disease in an HIV-1-infected patient treated with highly active
      antiretroviral therapy.

PMID- 16889176
TI  - Peripheral primitive neuroectodermal tumor of bowel mesentery in adults.

PMID- 16889177
TI  - Giant femoral abscesses due to suprapatellar pouch perforation.

PMID- 16889178
TI  - Fetal growth curves.

PMID- 16889179
TI  - Use of CAM in rheumatology.

PMID- 16889180
TI  - [Cardiotocographic monitoring (non stress test) in pregnancies, complicated by
      preeclampsia].
AB  - Cardiotocographic monitoring (NST) is well accepted in obstetrical practice. It
      provides direct and valuable information about neurological and myocardial
      function of the fetus. In a retrospective and prospective study, including 544
      preeclamptic women for period of 10 years cardiotocographic monitoring of the
      fetus was applied. At admission in 427 (82.80%) of the cases, CTG readings were
      found normal. In the rest of 89 (17.20%) preeclamptic patients the NST records
      were found pathological. A correlation between mean values of resistance indices
      (RI) of umbilical and uterine arteries (RI = 0.73; RI = 0.75 respectively) and
      pathological NST was demonstrated. A similar correlation is found for newborn's
      Apgar score at 5th minute--7.16. Although the difference is found statistically
      significant, it is not possible to conclude that Doppler velocimetry is more
      predictive than cardiotocographic records.

PMID- 16889181
TI  - [Intrauterine infection in cases with premature rupture of fetal membranes-
      incidence, structure].
AB  - OBJECTIVE: The study deals with the question about the real incidence of the
      intrauterine infection (IUI) after PROM; the correlation between the clinical
      manifestation of IUI and histological findings as well as its relationships with
      the incidence of the neonatal infections. DESIGN: Prospective study. METHODS AND
      PATIENTS: One hundred eighty two pregnant women with premature delivery and their
      newborn infants were included. Clinical and laboratory signs concerning the
      presence of IUI were followed. A histological study of the fetal membranes, cord
      and placenta was done classifying the inflammatory changes according to there
      severity. The newborn infants were observed for signs of neonatal infection.
      Juxtaposition between the clinical manifestation of the IUI and the morphological
      signs of inflammation in the fetal membranes, cord and placenta was done.
      RESULTS: In 114 women histological signs of IUI were found but clinical signs of
      IUI were observed in only 51 cases (44.7%), i.e. in the other 63 cases the
      infection ran subclinically. An incidence of 11.5% (21 cases) of neonatal
      infection after PROM was registered and in 20 of them there were histological
      signs of intrauterine infection (in 14 cases with umbilical cord involvement-
      66.7%). CONCLUSION: The cases with clinically manifested IUI do not reflect the
      real incidence of IUI--in about 34.5% of women with premature delivery infections
      run subclinically. There is a strong relationship between inflammatory changes in
      fetal membranes, cord and placenta and the neonatal infections. Among cases with
      severe inflammation (with fetal cord involvement) about one third of the newborn
      infants develop neonatal infections.

PMID- 16889182
TI  - [The efficacy of the misoprostol in cases of abnormal and pathologic hypotonic
      hemorrhage in the early puerperium].
AB  - The aim of this study is to determine the efficacy of the Misoprostol (Cytotec)
      in cases of abnormal and pathologic hypotonic hemorrhage in the early puerperium
      as a result of hypotonia of the uterus. MATERIAL AND METHODS: A group of 50 women
      with vaginal or abdominal labor developing hypotonic abnormal/pathologic bleeding
      after the placental delivery were given Misoprostol (Cytotec 200-400 microgr per
      rectum and/or per oral every 15 min). We compared this group with a control group
      without having postpartum bleeding. RESULTS: The application of Misoprostol
      resulted in uterine contraction and discontinuing the abnormal bleedings in both
      vaginal and Caesarian deliveries. The main blood lost in the next two hours
      period after vaginal labor didn't differ with the blood lost of the normal labors
      (66 ml vs. 75 ml). In the Caesarian deliveries the blood lost after application
      of the Misoprostol also didn't differ with the blood lost after normal caesarian
      section (78 ml vs. 80 ml). CONCLUSIONS: Misoprostol decreases the hypotonic
      uterine bleedings in the placental and early puerperal period. The significance
      of the Misoprostol in the group of therapeutic events is determined by its fast
      therapeutic effect, its convenient application and its good tolerance.

PMID- 16889183
TI  - [Therapeutic approach in locally advanced cervical cancer].
AB  - Patients with locally advanced cervical cancer (LACC) consist over 60% of
      diagnosed cases. They are therapeutic problem, because the more the stage
      increases,the more survival decreases,the incidence of lymph node metastases and
      the resistance to the treatment raises. Therapeutic approaches to each one of the
      stages,consisting the category LACC are presented in this study. Authors reported
      on the response rate to the applied therapy, operability urvival rate, sites of
      recurrences and distant metastases and the histopathological the postoperative
      specimen.

PMID- 16889184
TI  - [Use of yasmin in the treatment of women with polycystic ovary syndrome].
AB  - AIM OF STUDY: To prove the clinical efficiency over hyperandrogenism in women
      with PCOS after the application of the combined oral contraceptive Yasmin
      containing 30 mcg ethynilestradiol and 2 mg drospirenone. METHODS: Prospective
      open study over 15 women taking Yasmin for six months. At the beginning and at
      the end of the study the following values have been checked--the Ferriman-Gallwey
      /F-G/ index, BMI, the waist/hip ratio (WHR), some hormonal and biochemical
      indexes--testosterone, SHBG, immune reactive insulin (IRI), glucose, as well as
      the values of free androgenic index (FAI) and insulin resistance (HOMA). RESULTS:
      All fifteen women completed 6 months of therapy. The drug has been accepted very
      well. At the end of the study there was a significant improvement of hirsutism,
      expressed in the decrease of F-G index, accompanied by an increase of
      testosterone and SHBG values. The carbohydrate parameters haven't changed
      significantly. CONCLUSION: Yasmin is an effective drug in the treatment of
      hyperandrogenism in women with PCOS with few side effects and no significant
      influence over insulin resistance.

PMID- 16889185
TI  - [Use of aminoglycoside antibiotic gentamycin in extremely premature infants-
      administration schedule and suggested dosage based on pharmacokinetic studies in
      plasma].
AB  - The pharmacokinetics of Gentamycin administered to 22 infants intravenously at
      currently recommended doses (2-2.5 mg every 24 h for infants less than 7 days of
      life and 28 g.a. and 12 h for infants 32 g.a). The results showed a statistically
      significant relation between half-life and postconsiptional age and direct
      correlation between total body clearance and postconsiptional age. These
      pharmacokinetics data were used to calculate a new dosage schedule for preterm
      infants. Ondoing therapeutic drug monitoring is essential to tailor the dosage to
      the individual patient. Gentamycin.

PMID- 16889187
TI  - [The feeding of newborns with low birth weight with milk formula "Nenatal" and
      "Nutrilon-premium"].
AB  - The aim of the study is to make retrospective analysis of 9 years experience in
      the feeding of praematuries and high risk newborn in that ward in First City
      Hospital-Sofia with formula milks "Nenatal" and "Nutrilon-premium". 721--42.4%
      from all babies in this period were feed with those formulas. With Nenatal only-
      11.8%, with Nutrilon-premium 88.2%. This the fact is due that all babies under
      2000 gr. were fed with Nenatal, and after reaching 2000 gr.--with Nutrilon
      premium. The results confirm that Nenatal is right formula for feeding of low and
      very low birth weight infant, due to its special content and qualities. The
      results from Nutrilon-premium illustrated that mean gain weight is the biggest in
      I grade of prematurity--33 grams, followed by matures--30 gr, after them II grade
      -29 gr., III grade--27 gr., IV grade--26 gr. As a conclusion we may say that mean
      gain weight for all groups is 29 grams. Consuming all gain weight of the babies
      feeding with Nutrilon-premium data appear that the biggest is in III of
      prematurity--1499 grams, followed by IV grade--1418 gr., I grade--1341 spama, II
      grade--1219 gr., and last matures--745 gr.

PMID- 16889186
TI  - [Prevention of brain hemorrhage in infants with low and extremely low birth
      weight and infants treated with surfactants. Late observation].
AB  - Prematurely born infants with intraventricular haemorrhage (IVH) suffer
      significant morbidity and mortality, particularly those infants with high grade
      haemorrhage. The more premature infants have a higher incidence, experiencing
      more severe IVH. The etiology of IVH is clearly multifactorial. Prevention, both
      prenatal and postnatal. These include efforts to prevent preterm delivery.
      Postnatally, the importance of optimal resuscitation and neonatal care practices
      is stressed, particularly those which minimize cerebral blood flow fluctuation.
      130 premature infants of less than 32 weeks gestation with a very low birth
      weight (VLBW) and extremely low birth weight (ELBW) were studied. They were
      divided in four groups: group I (n=35) received Indocid; group II (n=42) received
      Indocid and Phenobarbital; group III (n=53) received Indocid and Phenobarbital;
      surfactant. These three groups were compare to a reference group (n=45). Newborns
      from the main group were given Indocid 0.1 mg/kg from 6-12 h of life and during
      next three days, Phenobarbital 5 mg/kg first five days after delivery and
      surfactant in the first 4 hours of life according to the protocol provided with
      the specific surfactant replacement product. Cerebral netrasaund in 24 hours, day
      3, 5 and 10 of life and follow up till one year age were performed. We found that
      IVH/PVH percentage is lowest in newborns from group III, followed by newborns
      from group II and group I.

PMID- 16889188
TI  - [Inborn anomalies in the development of Mullerian ducts--literature review].

PMID- 16889189
TI  - [Effect of oral contraceptives on vaginal flora].
AB  - The contraceptive and non contraceptive advantages of oral chormonal
      contraceptives as well as the good control on fertility, make it one of the most
      preffered method of contraception. The normal vaginal flora is a dynamic
      ecosystem and itsequilibrium and status of eubyosis amongst its inhabitants is an
      important mechanism against exogenous infections. The use of oral contraceptives
      is not associated with significant changes in the vaginal microbial flora; the
      normal concentration of the lactobacillli is preserved.

PMID- 16889190
TI  - [Placental angiogenic factors. Essentials and clinical significance in
      preeclampsia].

PMID- 16889191
TI  - [Three cases of vaginal adenosis after topical 5-fluorouracil therapy for vaginal
      HPV-associated lesions].
AB  - Three cases of vaginal adenosis after topical 5-fluorouracil therapy for vaginal
      HPV-associated lesions are reported. Three patients with colposcopic, histologic
      and viral evidences for subclinical papillomavirus infection (in combination with
      low-grade vaginal intraepithelial neoplasia in of them) are treated with 5-FU. In
      follow-up control examinations persistent ulcerations were found without
      regression after applied therapy. By colposcopic and histologic examinations
      vaginal adenosis was proved without histories of intrautering DES exposure. After
      the destructive therapy the reported lesions were regressed without appearance of
      new lesions in follow-up control examinations. The application of 5-fluorouracil
      has to be used only in cases of recurrent vaginal warts and in cases of high
      grade vaginal intraepithelial neoplasia with strict folow-up cytological and
      colposcopic control examinations.

PMID- 16889192
TI  - [Effectiveness of antihypertensive medications in patients with preeclampsia].
AB  - The presented study is retrospective and prospective in design. It is based on
      the medical records of Maternity hospital "Majchin dom" and planned studies
      during the period 1994-2005. 544 preeclamptic patients with singleton pregnancies
      were included. 334 (61.3%) of them were diagnosed with mild preeclampsia and 210
      (38.7%) had severe preeclampsia. Blood pressure was monitored at least four times
      daily, depending on the severity of the case with mechanical manometer. In
      special cases cardiopulsometry was applied. In order to compare the effectiveness
      of different antihypertensive medications, administered orally, either alone, or
      in combination (no antihypertensive medication, Methyldopa, Nifedipin, beta
      blockers and combinations between them), patients were divided in seven groups.
      The mean values of systolic and diastolic blood pressure, measured before
      delivery were compared. No statistically significant difference between the
      groups was noticed. We were not also able to find statistically significant
      difference in blood pressure measurements before delivery, between patients with
      severe preeclampsia, treated with parenteral Nepresol or Chlofazolin.

PMID- 16889194
TI  - [Using GnRH-agonists (Zoladex) in the treatment of genital endometriosis].
AB  - METHODS AND MATERIALS: The study is prospective and involves 112 patients
      suffering from pelvic endometriosis aging from 19-38 years. (28.6 average age).
      The disease was diagnosed via laparoscopy and the stage was determined using the
      revised AFS classification. Zoladex (Goserelin depot--3.6 mg) is being applied
      every 28 days for 6 months in the hypodermic tissue of the front abdomen wall.
      All patients are being examined monthly after every Zoladex application (for
      subjective complaints--dysmenorrheal, dyspareunea, pelvic pain; serum estradyol
      E2; amenorrhea; side effects) and every 24 months (recuperation of the menstrual
      cycle, pregnancy). RESULTS: In 88% of the patients amenohrea is obsereved in the
      first eight weeks of therapy. The menstrual cycle takes an avarege of 68 (31-139)
      after the last Zoladex application to reappear. At the end of the first month
      after the first application the serum level of estradyol E2 is lowered to a
      menopause level (from 750-800 to 120-130 Pmol/L) and it remains as low till the
      end of the treatment. Eight weeks after the completion of the therapy it goes
      back to its normal values. During the course of the first month of amenorrhea
      condition a 38% fall in the level of complaints (dysmenorrheal, dyspareunea,
      pelvic pain) is observed. After the 6th month 88% of the patients have no
      complaints. Side effects observed during the course of treatment include warm
      waves, sweating, vaginal dehydration (60-80%) which do not in any way disturb the
      patients to the point of quitting the therapy and do disappear with its end. The
      focus group contains 54 infertile patients with endometrioses willing to get
      pregnant. In 12 months after the completion of the treatment 16 of the patients
      become pregnant, followed by 12 more in the next one year. CONCLUSION: Zoladex
      causes amenorrhea, which lasts till the end of the treatement. It causes a rapid
      drop of the serum consentration to a menopause level. Causes a strong and durable
      treatment of the symptoms of endometriosis. The side effects disappear with the
      end of the therapy. The treatment is easy to go through and there no cases of a
      quitting patient. The treatment has a curable effect over the endometriosys and
      in cases of infertility provides a possibility for pregnancy.

PMID- 16889193
TI  - [Intrauterine infection in premature rupture of fetal membranes--dynamics].
AB  - One of the controversies in the theoretical and practical obstetrics is the
      relationship between the length of the latent period after the PROM and the
      incidence of the intrauterine infection (IUI). AIM OF THE STUDY: To establish how
      the incidence of IUI changes with the duration of the latent period after PROM.
      DESIGN: Prospective study. METHODS AND PATIENTS: Five hundred seventy six
      pregnant women with PROM and their newborn infants were included. The clinical,
      laboratory and histological signs of IUI were observed. The incidence of the
      cases with clinically manifested IUI, histologically approved IUI and neonatal
      infections at different length of the latent period were explored. RESULTS: The
      incidence of the inflammatory changes in the fetal membranes, umbilical cord and
      placenta increased progressively with the prolongation of the latent period,
      respectively--in 34.4% after 24 hours, 52.0% after 48 hours, 87% after the 72-th
      hour. Inflammatory changes in umbilical cord rised sharply from 8.0 to 47.8%
      after 72 hours from the PROM. Clinically manifested IUI and neonatal infection
      also rised sharply after the 72-th hour after the PROM, respectively--at 62.9%
      and 22.5%. CONCLUSION: There is a relationship between the incidence of the
      infectious complications and the duration of the latent period after the PROM.
      The risk of IUI rises sharply between the 24-th and the 72-th hour after the
      PROM.

PMID- 16889195
TI  - [New approaches to the treatment of advanced ovarian cancer].
AB  - With this research work our aim is to summarise the bulgarian and the experience
      of foreign /western/ authors in the field of treatment of the advanced ovarian
      cancer. We summerised the experience from the treatment of 250 patients for 5
      years period /from 2000 till 2006/. On the basis from the results of treatment we
      tried to produce algorrhythm, which can be used from the oncogynaecologists in
      their everyday practice. We are convinced that with the development of the
      oncogynaecological science and practice this algorrhythm can be bettered. The
      main therapeutical approaches for the treatment of the advanced ovarian cancer
      include: primary cytoreductive surgery, neoadjuvant and adjuvant chemotherapy,
      interval debulking, second look laparotomy, intestinal resections and
      anastomosis. Very often is made resection of the bladder and reanastomosis of the
      ureters. The use of new chemotherapeutics, radiotherapy, hormonal medicaments and
      immunotherapy will better the fight against the advanced ovarian cancer.

PMID- 16889196
TI  - [Anatomical and surgical meaning of the bladder during the performance of radical
      hysterectomy].
AB  - During the performance of radical hysterectomies in the everyday practice,
      oncologists continuously face difficulties and problems related to the urinary
      tract at the time of early and late postoperative period and occasionally
      intraoperatively. Bladder complications are hypo- and atonia, which may lead to
      hydroyreter and hydronephrosis. These hypo- and atonia sometimes delate adjuvant
      therapies and this influences therapeutic results. Thus in the present review are
      reported the blood supply, nerve structures and bladder function, which
      preserving may result in less complications after radical hysterectomy

PMID- 16889197
TI  - [Anatomical and surgical meaning of the ureters during the performance of radical
      hysterectomy].
AB  - During the pelvic surgery ureters are dissected until they flow to the bladder.
      For this reason surgen must be knowleadgable about the anatomy of the vesico
      ureteral unit and the blood supply of the ureters,because the majority of the
      early and late complications, especially following pelvic irradiation,are related
      to the function of kidneys and ureters. In the present review attention is paid
      on the ureters as an anatomical marker during the performance of radical
      hysterectomy and on the possible intraoperative complications, identification and
      avoidance of ureteral injuries,as well. Authors also discussed on the management
      of ureteral damages.

PMID- 16889198
TI  - [Whether long-term use of oral contraceptives and hormone replacement therapy
      affects the pathology of mammary gland?].
AB  - The authors presented a retrospective analysis of the risk of using hormonal
      drugs in 162 women over a period of 5 years, which were operated for benign and
      malignant diseases of the mammary gland. For comparison we have used a control
      group of 100 women presenting with pathology of the mammary gland, without use of
      hormonal drugs, for the same period of time. The patients have been selected
      according to their age, parity, body weight, menarche, time of beginning of
      menopause, continuity of using and a daily dose of hormonal drug, history of
      gynecological operations, type of pathological changes in mammary gland and the
      range of surgical intervention for their treatment. It is proved by dispersion
      analysis the presence or the absence of statistical difference in the pathology
      of mammary gland between the studied and the control group in reference to the
      described risk factors.

PMID- 16889199
TI  - [Thrombophilia and pregnancy].
AB  - The incidence of venous thromboembolism is increased five to six times in
      pregnancy; and it is estimated that thromboembolic episodes- superficial and deep
      venous thromboembolism and pulmonary embolism occur in 1:1000 to 1:1500
      pregnancies. These complications during pregnancy and puerperium, are not common
      but serious and leading cause of maternal morbidity and mortality. Thrombophilias
      -acquired or inherited, result of anticoagulant regulatory proteins deficiency,
      could compromise normal pregnancy by increasing the risk of developing first or
      recurrent thromboembolic incidents and adverse obstetric events.

PMID- 16889200
TI  - [Inborn bacterial infections during neonatal period].
AB  - Considering the high mortality and serios morbilidy associatent with neonatal
      infections. A competent diagnostic marker also needs to have reasonably high
      specificity. Good evidence exists to support the use of CRP measurements in
      conjunction with other established diagnostic tests (such as a white blood cell
      (WBC) count with differential and blood culture) to establish or exclude the
      diagnosis of sepsis in full-term or near-term infants. Sepsis was suspected
      within the first 3 days after birth in. There were 20% early-onset and 53% late
      onset episodes of proven sepsis. CRP had sensitivities of 39.4% and 64.6% for
      proven or probable sepsis and 35.0% and 61.5% for proven sepsis in early-onset
      and late-onset episodes, respectively. To compare the clinical informative value
      of and C-reactive protein (CRP) plasma concentrations in the detection of
      infection and sepsis and in the assessment of severity of sepsis. PCT is a better
      marker of sepsis than CRP. The course of PCT shows a closer correlation than that
      of CRP with the severity of infection and organ dysfunction. Diagnostic markers
      are useful indicators of neonatal bacterial infections C-reactive protein (CRP),
      procalcitonin (PCT) Intralevcin 6, 8 are early sensitive markers of infection.

PMID- 16889201
TI  - [Acute intermittent porphyria and pregnancy (case report)].
AB  - A case of acute intermittent porphyria [AIP] known before pregnancy is reported
      in a patient who delivered by elective caesarean section. The pathogenesis of the
      disease, its symptoms and diagnosis are described as well as specific aspects of
      its clinical manifestation and differential diagnosis during pregnancy The
      therapeutic approach both during and out of pregnancy is discussed.

PMID- 16889202
TI  - [Multiple sclerosis and pregnancy (two additional cases)].
AB  - The authors made a short analysis of the epidemiology, etiology, pathogenesis,
      clinical presentation and treatment of multiple sclerosis. There were presented
      facts about the influence of pregnancy over the progress of this neurological
      disease, and the effect of multiple sclerosis on the pregnancy and delivery
      development. There also were described two clinical cases of pregnant women with
      multiple sclerosis, who delivered in the last 10 years in Clinic of Obstetrics in
      MBAL-Pleven.

PMID- 16889203
TI  - [Multa et multum].

PMID- 16889204
TI  - [To the history of organisation and development of cardiac anesthesiology in the
      A. N. Bakulev Research Center of Cardiovascular Surgery of the Russian Academy of
      Medical Sciences: the start of activities (1956-1965)].
AB  - The authors present data on the development and introduction of anesthetic
      techniques during cardiac surgery at the Institute of Thoracic Surgery, USSR
      Academy of Medical Sciences, in 1956-1960 and after its reorganization to the
      Institute of Cardiovascular Surgery, USSR Academy of Medical Sciences, in 1961
      1965. It is shown that in the years of introduction of closed operations on the
      heart, the methods of one- and many component inhalational anesthesia were
      mastered, its techniques were developed, anesthesia apparatuses and an anesthesia
      schedule were designed, cardiac anesthesiological studies were conducted,
      training of physicians from the country's regions was initiated, and the first
      guidelines for general anesthesia were published. In these years, the firm
      foundation was laid for the development of cardiac anesthesia. Later on the
      Institute developed and introduces all basic types of inhalational anesthesia
      during operations on the open heart under both extracorporeal circulation and
      hypothermia. The gained experience allowed the laboratory staff to defend several
      dissertations, to issue two monographs, and to analyze errors and risks of
      general anesthesia in patients with cardiovascular diseases at surgery.

PMID- 16889205
TI  - [Anesthesiological provision of patients with tachyarrhythmias during radio
      frequency ablations].
AB  - The paper presents the results of anesthesia in 55 patients aged 18 to 70 years
      during radio-frequency ablation for different types of tachycardias.

PMID- 16889206
TI  - [The clinical and diagnostic value of some hemodynamic indices for the assessment
      of silent ischemia in patients with low myocardial contractility].
AB  - During initial anesthesia, central and peripheral hemodynamic parameters were
      studied in 32 patients operated on for coronary heart disease (CHD). The patients
      were divided into 3 groups: 1) those with < 35% ejection fraction (EF) with
      postinfarct left ventricular (LV) aneurysm (PLVA); 2) those with > 35% EF with
      PLVA; 3) those with > 35% EF without PLVA. All the examinees were assigned as
      having NYHA functional class III-IV. During the study, the authors examined
      central and peripheral hemodynamic parameters: ECG, invasive blood pressure (BP),
      pulmonary pressure, central venous pressure, and cardiac output. The findings
      were used to calculate cardiac index (CI) and its changes (CI). In addition, the
      indices of rate pressure product, a marker of myocardial contractility and the
      Buffington index (I baf) is a BPmean-heart rate ratio), a marker of possible
      myocardial ischemia, were calculated. To gain some insight into the role of
      ischemia in the reduction of SI in the examinees, the authors modified the index
      I baf: they used the index perfusion pressure in the coronary bed instead of
      BPmean in the formula.

PMID- 16889207
TI  - [Pathophysiology of the brain lesion during operations with extracorporeal
      circulation].

PMID- 16889208
TI  - [Experience with epidural anesthesia during myocardial revascularization
      operations].
AB  - The paper presents the results of 213 myocardial revascularization using epidural
      anesthesia. The used anesthesiological protocol combining intravenous proforol
      sedation and epidural naropine block proved to be effective and safe and ensured
      adequate anesthesia that made possible myocardial revascularization both without
      using extracorporeal circulation (transmyocardial laser revascularization, mini
      invasive myocardial revascularization) and with complex repairs of the geometry
      of the left ventricle and cardiac valvular apparatus and provides a means for the
      activation of patients and extubation on the operating table in the absence of
      surgical complications, hemorrhages, and extracorporeal circulation procedures
      even after reconstructive surgery.

PMID- 16889210
TI  - [Inflammatory response mediators in newborns and infants with congenital heart
      diseases during surgical treatment under extracorporeal circulation].
AB  - Surgical treatment of complex congenital heart disease under extracorporeal
      circulation is accompanied by a systemic inflammatory reaction occurring in
      neonatal infants and babies. There were drastic increases in the concentration of
      tumor necrosis factor, interleukin-8, neutrophilic elastase and a predominance of
      a proinflammatory response over an inflammatory one at the warming stages and
      after administration of protamine sulfate. The rate of an inflammatory response
      depended on the duration of extracorporeal circulation. Modified ultrafiltration
      could remove cytokines; however, their concentration in the body remains high. A
      relationship was found between the course of a postoperative period and the rate
      of a developing reaction to extracorporeal circulation in the surgical treatment
      of congenital heart diseases.

PMID- 16889209
TI  - [The plasma level of an inactive moiety of B-type natriuretic peptide precursor
      as a predictor of cardiac function during operations under extracorporeal
      circulation].
AB  - Ventricular cardiomyocytes secrete brain natriuretuc peptide (BNP) and an
      inactive moiety of its precursor (nt-proBNP). It is recommended the blood level
      of the latter should be monitored to ascertain the severity of myocardial lesion.
      This investigation was undertaken to study the diagnostic and prognostic value of
      a substantial increase in blood nt-proBNP levels (600 pg/ml or more) in patients
      operated on under extracorporeal circulation. Thirty-eight patients operated on
      for coronary heart disease were examined. Before surgery, the plasma
      concentration of nt-proBNP had been determined by electrochemiluminescence
      (Elescys, Roche). According to plasma nt-proBNP levels, the patients were divided
      into 2 groups: 1) 24 patients with nt-proBNP levels of less than 600 pg/ml; 2) 14
      patients with its levels of 600 pg/ml or more. Group 1 patients showed signs of
      diastolic dysfunction of the right ventricle: the lower ratio of its early to
      atrial filling linear velocity integrals and the increased end-diastolic volume
      index. In the postperfusion period, nt-proBNP is a significant independent
      predictor of left ventricular function. The patients with the baseline nt-proBNP
      levels of above 600 pg/ml were found to have decreases in ejection fraction of
      the left ventricle and in its pump ratio along with elevated pulmonary wedge
      pressure.

PMID- 16889211
TI  - [Evaluation of the safety of auxiliary venous drainage in the surgical treatment
      of patients with acquired cardiac diseases].
AB  - The present study has comparatively analyzed two procedures of auxiliary venous
      drainage: 1) that by means of vacuum (VaVD), 2) that using an additional roller
      pump (ARP) and the conventional extracorporeal circulation (EC) with gravitation
      venous drainage (GVD). The material for the study was the number of microembolic
      signals (MES) in the middle cerebral artery bed and neurological disorders in
      patients operated on for cardiac valvular diseases. According to the venous
      drainage procedure, the patients (n = 90) were divided into 3 groups: 1) those (n
      = 30) with traditional GVD; 2) those (n = 30) with VaVD; 3) those (n = 30) with
      ARP. The study revealed the impact of different venous drainage procedures on the
      number of MES and the patients' neurological status.

PMID- 16889212
TI  - [Clinical experience with voluven solution used as a basic component for pump
      oxygenator filling during operations on the cardiac valves and coronary
      arteries].
AB  - The present study comparatively analyzed the clinical effects of three solutions
      used to fill an extracorporeal circulatory circuit (ECCC). The arterial and
      venous blood samples taken from patients operated on for valvular disease and
      coronary heart disease were studied. All patients (n = 61) were divided into 3
      groups according to the basic component of the primary volume of ECCC filling: 1)
      Ringer's crystalloid solution; 2) gelofusin; 3) the hydroxyethyl starch 130/0.4
      Voluven. The resultant samples were examined for the following parameters: a)
      hematological: the levels of formed blood elements, hemoglobin, erythrocytic
      hemoglobin, and free hemoglobin and the histograms of leukocytes, erythrocytes,
      and platelets; b) physicochemical: arterial and venous blood pH, pO2, pCO2,
      SatO2; c) biochemical: blood electrolytic balance and lactate levels. The values
      of hemoglobin, hematocrit, and blood gas composition were used to calculate
      oxygen consumption (ml/min x m2). The parameters of central hemodynamics and the
      temperatures in the rectum, esophagus, and venous oxygenator port were
      continuously monitored during extracorporeal circulation (EC). At its end,
      overall diuresis and water balance were determined. The plasma-substituting
      effect of Voluven was found to be highly effective during a clinical study. The
      found beneficial properties of the agent may be particularly attractive while
      applying EC to the surgery of acquired heat diseases when the duration of an
      operation and, accordingly, extracorporeal support forces the physician to
      administer large solution doses many times.

PMID- 16889213
TI  - [Perioperative hemodynamic monitoring in cardiosurgical patients: new
      potentialities and old shortcomings].

PMID- 16889214
TI  - [Intensive care for newborns and infants after anatomic correction of
      transposition of great vessels].
AB  - A retrospective study was made in 48 babies undergone an arterial switching
      operation at the Bakulev Research Center of Cardiovascular Surgery in January
      2004 to September 2005. Their age at surgery was 5 days to 11 months; body
      weight, 3.9 +/- 1.1 kg (2.4-8.7 kg). According to the course of a postoperative
      period, the patients were divided into 2 groups: 1) 28 (58.3%) neonates with
      simple transposition of great vessels (TGV) and older babies (above 3 weeks of
      life) with simple TGV; 2) 20 (41.6%) patients with TGV + ventricular septal
      defect. The postoperative management of all the patients was based on the delayed
      bringing the sternum together in babies at risk for close mediastinum syndrome,
      on the reduction in left and right ventricular afterload with the mean blood
      pressure (BPmean) minimally sufficient to maintain adequate coronary blood flow
      and diuresis, by using inodilatators and nitric oxide (II) and by limiting the
      volume of administered fluid. The sternum was primarily brought together in 20
      (41.6%) patients, in 13 (27.1%) on day 2. Sternal separation was required in 1
      patient from Group 1 on postoperative day 2. The duration of artificial
      ventilation was 3.3 +/- 5.2 days (0.7-15 days); the length of stay in an
      intensive care unit was 4.8 +/- 8.2 days (1-20 days). There were 9 (18.7%)
      deaths. Left ventricular failure, high pulmonary hypertension, and coronary
      insufficiency were causes of death in 2 (4.8%), 1 (2.4%), and 2 (4.8%) patients,
      respectively. After arterial switching, the optimum management of patients with
      low cardiac output is to maintain low peripheral resistance and to restrict
      preload and to use FDE III inhibitors as the drugs of choice.

PMID- 16889215
TI  - [Acute respiratory distress syndrome in pediatric cardiosurgery].
AB  - The prognosis in acute respiratory distress syndrome (ARDS) is poor; its
      mortality is generally 40-60%. The mortality in patients with ARDS is more
      commonly associated with the sequels of sepsis and multiple organ dysfunction
      than with respiratory failure although the latest papers on protective
      ventilation suggest that death in these patients directly results from lung
      lesion in a number of cases. There have been encouraging data on the reduced
      mortality rates due to acute lung lesion/ARDS in the past decade. The development
      and introduction of new technologies of respiratory support, the emergence of new
      effective treatments for sepsis, and the improvement of general maintenance
      therapy in patients with ARDS may be a possible explanation for such changes for
      the best.

PMID- 16889216
TI  - [The arsenal of extracorporeal circulation systems in pediatric cardiosurgery].
AB  - The paper presents the arsenal of extracorporeal circulation systems used in the
      surgical treatment congenital cardiac diseases. It provides some experience in
      using the extracorporeal circulation systems, indications for and
      contraindications for their use, and a working classification of extracorporeal
      circulatory techniques. Their methodological features, criteria for the adequate
      use of extracorcopreal techniques, and the results of their application are
      described.

PMID- 16889217
TI  - [The time course of changes in early postoperative echocardiographic parameters
      in patients after reparative operations on the left ventricle and coronary bypass
      surgery].
AB  - The echocardiographic functional features of the left ventricle after its
      geometrical reconstruction in combination with myocardial revascularization were
      studied in 31 patients. The most significant parameters were defined, by
      evaluating the course of an early postoperative period.

PMID- 16889218
TI  - [Hybrid technologies of renal replacement therapy in the treatment of multiple
      organ failure in cardiosurgical patients].
AB  - Composite reparative cardiosurgical operations frequently lead to ischemia and
      hypoxia of vitally important organs and systems, which may be later a cause of
      the multiple organ dysfunction syndrome (MODS). Up to now, after operations on
      the heart and vessels, the incidence of this menacing complication remains rather
      high. In the postoperative period, isolated acute renal failure (ARF) occurs
      extremely rarely; its incidence is not greater than 5-8% whereas ARF is much more
      frequently (as high as 90%) a component of MODS and an indicator of a patient's
      status. Among patients undergoing cardiac resuscitation, ARF is encountered in 20
      27% of cases, 71.7% of them need replacement renal therapy (RRT). The latter
      should be regarded as an intermediate treatment that allows the patient to
      survive up to the time that native kidney function restores. Choice of an
      adequate and effective treatment option for acute renal dysfunction remains to be
      urgent. On-going discussions between the advocates of continuous RRT (CRRT) and
      the adherents of intermittent RRT (IRRT) are a prominent case in point. These two
      modalities have a variety of good and bad points. In this connection, there is an
      idea of developing hybrid procedures that can combine the best properties of both
      IRRT and CRRT in order to use them in the treatment of critically ill patients
      with multiply organ dysfunction and, judging from the first not numerous
      publications, their application has reduced the incidence of complications due to
      routine extracorporeal blood purifying procedures.

PMID- 16889219
TI  - [Significance of the blood homeostasis and rheology studies for the prevention
      and treatment of hemorrhages].

PMID- 16889220
TI  - [Complex intensive care for acute gastroduodenal hemorrhages in patients after
      operations on the heart and vessels].
AB  - The purpose of the study was to define the most effective principles of intensive
      care for acute gastroduodenal hemorrhages in patients undergoing operations on
      the heart and vessels. The outcomes of 13,345 operations on the heart and
      vessels, performed at the A. N. Bakulev Research Center of Cardiovascular
      Surgery, Russian Academy of Medical Sciences, were analyzed. Gastroduodenal
      hemorrhages were diagnosed in 114 patients, which amounted to 0.8% of the total
      number of operated patients. In the vast majority (86.8%) patients,
      gastroduodenal hemorrhages occurred after surgery under extracorporeal
      circulation. The results of medical and surgical treatment were analyzed. The
      medical treatment for gastroduodenal hemorrhages included intensive drug therapy
      and endoscopic hemostasis. The comprehensive and intensive approach to performing
      antiulcer therapy (concomitant use of the antisecretory agents: proton pump
      inhibitors, gastric protectors, and reparative agents) could reduce the incidence
      of recurrent bleeding and the timing of epithelization of gastrointestinal
      mucosal defects. Analyzing the results of the treatments has indicated that the
      efficiency of conservative measures significantly exceeds the beneficial effect
      of the treatment of gastroduodenal bleedings, including urgent abdominal surgical
      interventions. Emergency surgical interventions for gastroduodenal hemorrhages in
      cardiosurgical patients deteriorate the postoperative period and lead to an
      increase in postoperative morbidity, which determines the expediency of their
      performance only when conservative measures are ineffective. An algorithm of
      tactical actions has been developed for gastroduodenal hemorrhages occurring
      after operations on the heart and vessels.

PMID- 16889221
TI  - [Systemic inflammation after operations on the open heart: significance of a
      microbial factor].
AB  - The given review of the literature discusses, from the present standpoints, the
      pathogenetic, clinical, and diagnostic aspects of a systemic inflammatory
      reaction developing during cardiac surgery under extracorporeal circulation.
      There is evidence that endogenous infection is of importance in developing
      systemic inflammation during cardiosurgical interventions. Current approaches to
      the early diagnosis of systemic bacterial inflammation, by applying the
      procalcitonin test and the chromatographic mass-chromatographic technique are
      proposed. The prevention of systemic inflammation and its sequels is considered.

PMID- 16889222
TI  - [Diagnostic and therapeutic aspects of pneumonias after cardiosurgical operations
      associated with artificial ventilation].
AB  - Artificial ventilation (AV)-associated pneumonias are the most common infectious
      complication in cardiosurgery. This prospective comparative study covered 50
      patients with AV-associated pneumonias occurring after surgery under
      extracorporeal circulation (EC). All the patients received the routine
      perioperative antibiotic prevention regimen (cefuroxime or ceftriaxone).
      According to the initial therapy, the patients with evolving pneumonia, the
      patients were divided into 2 groups: 1) those were given cefuroxime (maxipim); 2)
      those receiving a combination of maxipim or clarithromycin (clacid). The analysis
      has indicated that if pneumonia develops after surgery under EC, then this most
      frequently occurs in the first 5 postoperative days, i.e. early AV-associated
      pneumonias are prevalent. In cases of concurrent pneumonia, the duration of EC,
      the length of stay in an intensive care unit, and the total period of hospi-
      talization considerably increase. For cardiosurgical patients, the laboratory
      guide for establishing the diagnosis of AV-associated pneumonia is the elevated
      blood cell levels of more than 15 x 10(9)/l, unlike those of more than 10 x
      10(9)/l proposed for most patients. The etiology of AV-associated pneumonia is
      shown to vary with the timing of complication occurrence. There is evidence for
      the involvement of intracellular microorganisms (Chlamydia, Mycoplasma) in the
      development of early AV-associated pneumonias in at least every 10 patients. The
      advantages of a study of bronchoalveolar lavage samples over that of endotracheal
      aspirates for the etiological diagnosis of pneumonias were revealed. The
      advisability of prescribing a combination of a beta-lactam antibiotic (third- or
      fourth-generation cephalosporin) and a macrolide (clarythromycin) in early AV
      associated pneumonias is warranted. The objective criterion for the adequacy of
      this combination is positive changes in the marker of severe bacterial infections
      (procalcitonin). An algorithm is offered for antibacterial therapy for AV
      associated pneumonias developing after cardiosurgical operations, which considers
      the performed antibiotic prevention and the timing of pneumonia development.

PMID- 16889224
TI  - Backup programs in drug discovery.

PMID- 16889223
TI  - [Cardiac pump function during high-frequency ventilation].

PMID- 16889225
TI  - Target selection and pharma industry productivity: what can we learn from
      technology S-curve theory?
AB  - The number of new drug approvals per annum has been decreasing regularly over the
      past decade, and changes made 12 to 15 years ago to the research and development
      approach of the pharmaceutical industry may have contributed to this fall in
      productivity. In particular, the rapid switch at that time away from an
      'observation-led' approach toward a 'hypothesis-led' approach to target selection
      may be a key contributing factor to this issue. The strengths and weaknesses of
      both approaches are analyzed herein, and it is suggested that unsolved weaknesses
      in both approaches are holding back the productivity of the
      pharmaceutical/biotechnology industry.

PMID- 16889226
TI  - Exploiting QSAR methods in lead optimization.
AB  - Quantitative structure-activity relationship (QSAR) models play a key role in
      lead optimization, where the focus is on increased efficiency and lower
      attrition. When experimental data becomes rate limiting, a suitable model can
      bridge the experimental resource gap and direct investigation of a lead series
      toward productive lines. Technically, QSAR models can be readily generated and
      published to a wide community via the World Wide Web. We therefore focus this
      review on issues affecting model quality rather than on cataloguing models that
      are available. We also review the area of inverse QSAR, in which a model can be
      harnessed to semi-automated methods to provide an efficient way to explore vast
      areas of chemical space.

PMID- 16889227
TI  - Expediting drug discovery: recent advances in fast medicinal chemistry-
      optimization of hits and leads.
AB  - This article reviews the literature from January 2004 to January 2006 relating to
      the use of parallel chemistry compound libraries in drug discovery. Examples of
      libraries that have yielded active compounds across a range of biological targets
      are presented, together with synthetic details where relevant. The background of
      the biological target, and any structure-activity relationship that can be
      discerned from members of a library series, are also commented upon. A brief
      discussion of new technological developments in library design and synthesis, and
      likely future directions for parallel chemistry in the context of drug discovery,
      is also presented.

PMID- 16889228
TI  - Rational approaches to natural-product-based drug design.
AB  - Natural-product-based drug discovery has encountered significant challenges
      during the past decade. In recent years the pharmaceutical industry has placed
      low emphasis on natural-product-based drug discovery efforts because of an
      increasing reliance on newer technologies, such as combinatorial synthesis and
      high-throughput screening, and their associated approaches to drug discovery.
      However, recent natural-product-based lead-identifying strategies have
      successfully and rapidly integrated rational approaches that exploit and evolve
      the structural diversity provided by nature. These rational approaches include
      the application of structure- and ligand-based design, relationship building
      between biosynthetic enzymes and targets as well as within the target and natural
      product scaffold space, and biology-oriented synthesis-guided library design.
      This review focuses on the recent clinical and preclinical development of natural
      product-based compounds derived from these rational approaches, and is organized
      according to disease areas as well as novel concepts that may provide a rational
      basis for future developments.

PMID- 16889229
TI  - Nuclear magnetic resonance in target profiling and compound file enhancement.
AB  - Nuclear magnetic resonance (NMR) has matured as an important tool in drug
      discovery and development, with firm establishment of its roles in lead
      generation and optimization through application of NMR-based fragment screening
      and structure-based drug design. Besides these applications, NMR technology has
      expanded to make contributions both earlier and later in the drug discovery
      process. This review will focus on the impact of NMR in the early stages of drug
      discovery, in particular in characterizing the viability of targets for further
      discovery exercises and improving high-throughput screening through compound file
      enhancement initiatives.

PMID- 16889230
TI  - Advances in cathepsin S inhibitor design.
AB  - Cathepsin S is expressed in antigen-presenting cells and plays a role in
      invariant chain processing and major histocompatibility complex class II (MHCII)
      antigen presentation leading to CD4+ T-cell activation. An oral cathepsin S
      inhibitor that blocks MHCII antigen presentation could result in a T-cell
      selective immunosuppressant agent with improved safety over the current standard
      of care for the treatment of rheumatoid arthritis, psoriasis, multiple sclerosis
      and other autoimmune-based inflammatory diseases. This review focuses on advances
      in cathepsin S inhibitor utility and design since January of 2004.

PMID- 16889231
TI  - Targeting Hsp90 for the treatment of cancer.
AB  - Heat shock protein (Hsp)90 is a molecular chaperone that is responsible for the
      correct folding of a large number of proteins, which allows these proteins to
      achieve their functional conformation. Client proteins of Hsp90 include many
      overexpressed or mutated oncogenes that are known to be critical for the
      transformed phenotype observed in tumors. The compounds 17-AAG (Kosan Biosciences
      Inc/National Cancer Institute) and 17-DMAG (Kosan Biosciences Inc/National Cancer
      Institute) are Hsp90 inhibitors that are derived from the prototypical ansamycin
      natural product Hsp90 inhibitor geldanamycin. These compounds have demonstrated
      preclinical efficacy in mouse xenograft models, and are now undergoing phase II
      and I clinical trials, respectively. Preclinical efficacy studies of these
      compounds are collated and discussed in this review. More recent disclosures of
      small-molecule Hsp90 inhibitors include purine and resorcinol analogs, and the
      first small-molecule Hsp90 compounds showing oral efficacy have been described.
      Inhibition of Hsp90 not only results in the degradation of client proteins, but
      also results in the induction of another chaperone, Hsp70. Hsp70 is known to be
      anti-apoptotic, and therefore the induction of Hsp70 may ultimately limit the
      efficacy of Hsp90 inhibitors under certain circumstances. Histone deacetylase
      inhibitors have recently been demonstrated to exert some of their effect through
      modulation of Hsp90 chaperoning activity, and some mechanistic aspects of this
      control are also discussed herein.

PMID- 16889232
TI  - Recent advances in the discovery of melanin-concentrating hormone receptor
      antagonists.
AB  - In recent years, obesity therapy has become a major focus of pharmaceutical
      research. The worldwide market for obesity therapeutics has increased
      dramatically over tile past decade, and obesity has been linked with numerous co
      morbidities. Tile discovery of the role of melanin-concentrating hormone (MCH) in
      the regulation of energy homeostasis has attracted tile interest of several
      research groups worldwide. In conjunction with energy balance, a growing body of
      evidence suggests that MCH is also involved in the regulation of certain types of
      behavior, including anxiety and depression. Major developments in tile discovery
      of MCH receptor antagonists over tile past year, including the demonstration of
      oral efficacy in several rodent models for the treatment of obesity, as well as
      depression and anxiety, will be highlighted in this review.

PMID- 16889233
TI  - Growth hormone secretagogue receptor antagonists as anti-obesity therapies? Still
      an open question.
AB  - Ghrelin woas recently de-orphaned as an endogenous ligand of growth hormone
      secretagogue receptor (GHS-R), and is implicated as a short-term meal initiator
      and a long-term energy balance regulator. Administration of ghrelin causes
      increases in food intake and body weight in both rodents and humans. Inhibiting
      its actions with GHS-R anti-sense oligonucleotides, anti-ghrelin antibodies, and
      peptide antagonists leads to decreased food intake and weight loss in rodents.
      Despite the much-publicized promise of providing a novel approach for anti
      obesity treatment, limited progress has been made in developing small-molecule
      GHS-R antagonists and no such compound has been advanced to clinical trials. This
      review will summarize the recent progress in small-molecule GHS-R antagonists and
      offer some insight into this area of research based on the experience at Abbott
      Laboratories.

PMID- 16889234
TI  - Recent developments in CCR3 antagonists.
AB  - Selective eosinophil recruitment into inflammatory sites and their subsequent
      activation is a characteristic of allergic diseases, such as asthma, rhinitis and
      atopic dermatitis. CC chemokine receptor-3 (CCR3) is the principal mediator of
      eosinophil chemotaxis and is expressed on a variety of inflammatory cells
      associated with allergic responses; these cells include basophils, mast cells and
      T-helper-2 lymphocytes, and resident tissue cells such as airway epithelium.
      Animal studies suggest that CCR3 is a prominent mediator of allergic responses
      and that antagonizing the receptor will lead to a reduction in airway
      inflammation. The potential importance of CCR3 in allergic inflammation has made
      this receptor a target for drug development. This review summarizes the efforts
      in this research area that have been reported in the last two years.

PMID- 16889235
TI  - Key features of successful BNR operation.
AB  - Biological phosphorus removal has come of age after having been introduced with
      the treatment plants for the city of Johannesburg, South Africa, in 1974. There
      is a large number of plants in the world today and a great variety of basin
      configurations is used. Generally, we see excellent performance with the right
      wastewater characteristics and the correct design and operation, but there are
      still some issues not fully understood that have led to the perception that
      biological phosphorus removal is unreliable and unpredictable. These issues
      include nitrates in the feed, excessive return activated sludge recycle rates,
      secondary release of phosphorus and toxicity. This paper focuses on some of the
      issues that still frustrate designers and plant operators. There are also many
      claims for excellent removal by plants that appear not to conform to the
      established requirements for biological phosphorus removal. There is normally an
      explanation if the full picture is considered. The conclusion is that biological
      phosphorus removal is predictable and reliable if the process is properly
      understood.

PMID- 16889236
TI  - Biological treatment of sludge digester liquids.
AB  - Nitrogen removal in side stream processes offers a good potential for upgrading
      wastewater treatment plants (WWTPs) that need to meet stricter effluent
      standards. Removing nutrients from these internal process flows significantly
      reduces the N-load to the main treatment plant. These internal flows mainly
      result from the sludge processing and have a high temperature and a high
      concentration of ammonia. Therefore, the required reactor volumes as well as the
      required aerobic SRT are small. Generally, biological treatment processes are
      more economical and preferred over physical-chemical processes. Recently, several
      biological treatment processes have been introduced for sludge water treatment.
      These processes are available now on the activated sludge market (e.g. SHARON,
      ANAMMOX and BABE processes). The technologies differ in concept and in the
      limitations guiding the application of these processes for upgrading WWTPs. This
      paper reviews and compares different biological alternatives for nitrogen removal
      in side streams. The limitations for selecting a technology from the available
      ones in the activated sludge market are noted and analysed. It is stressed that
      the choice for a certain process is based on more aspects than pure process
      engineering arguments.

PMID- 16889237
TI  - Chemical phosphorus removal to extremely low levels: experience of two plants in
      the Washington, DC area.
AB  - Chemical phosphorus removal using metal (iron and aluminium) salts is frequently
      used to control effluent soluble phosphorus levels in wastewater treatment
      plants. In the Washington DC area effluent phosphorus requirements are extremely
      stringent to protect the Chesapeake Bay. Full-scale data from two plants in the
      area were analysed to establish phosphate behaviour in the presence of iron.
      Titration experiments and mathematical modelling were performed to determine the
      role of ferric phosphate and hydroxide precipitation and other mechanisms that
      may potentially be involved in phosphorus removal. Iron addition is described in
      the model using a chemical equilibrium approach extended with surface charges and
      adsorption. The model verifies key observations from full-scale data: (a)
      extremely low orthophosphate levels can be achieved over a wide range of pH
      values, (b) a mixture of ferric phosphate and ferric hydroxide precipitate is
      forming with the hydroxide acting as sorbent, (c) molar ratios of Fe/P (iron
      dosed to phosphate removed) vary widely (1.0-3.9) based on the technology used
      and residual phosphate levels. The model will be a useful tool for engineers to
      optimise preliminary, simultaneous and tertiary P removal, both for design and
      plant operation.

PMID- 16889238
TI  - Calcium effect on enhanced biological phosphorus removal.
AB  - The role of calcium (Ca) in enhanced biological phosphorus removal and its
      possible implications on the metabolic pathway have been studied. The experience
      has been carried out in an SBR under anaerobic-aerobic conditions for biological
      phosphorus removal during 8 months. The variations of influent Ca concentration
      showed a clear influence on the EBPR process, detecting significant changes in
      Y(PO4). These Y(PO4) variations were not due to influent P/COD ratio, pH,
      denitrification and calcium phosphate formation. The Y(PO4) has been found to be
      highly dependent on the Ca concentration, increasing as Ca concentration
      decreases. The results suggest that high Ca concentrations produce "inert"
      granules of polyphosphate with Ca as a counterion that are not involved in P
      release and uptake. Furthermore, microbiological observations confirmed that
      appreciable changes in PAO and GAO populations were not observed. This behaviour
      could suggest a change in the bacterial metabolic pathway, with prevailing
      polyphosphate-accumulating metabolism (PAM) at low influent Ca concentration and
      glycogen-accumulating metabolism (GAM) at high concentration.

PMID- 16889239
TI  - Insitu bioaugmentation of nitrification in the regeneration zone: practical
      application and experiences at full-scale plants.
AB  - Nitrification is the rate-limiting process in the design of activated sludge
      process. It is especially unstable during the winter season (when the temperature
      of activated sludge mixed liquor drops below 13 degrees C). It is therefore
      difficult to meet the ammonia effluent standards in winter. The common way to
      compensate for low nitrification rates at low temperatures is to increase sludge
      retention time (SRT). However, the increase of SRT is accompanied by negative
      factors such as elevated sludge concentration, higher sludge loading of secondary
      clarifiers, formation of unsettleable microflocs, etc. The low performance of
      nitrification at low temperatures can also be compensated for by enhancing the
      nitrification population in activated sludge. This paper describes such a method
      called bioaugmentation of nitrification in situ. This procedure takes place in a
      so-called regeneration tank, which is situated in the return activated sludge
      stream. The results of the operation of two wastewater treatment plants with
      regeneration zones are described in this paper, together with some economic
      evaluation of the bioaugmentation method.

PMID- 16889240
TI  - Hydrolysis of return sludge for production of easily biodegradable carbon: effect
      of pre-treatment, sludge age and temperature.
AB  - Return sludge from two Swedish and two Danish wastewater treatment plants were
      hydrolysed in laboratory reactors. Treatment plants with/without pre
      sedimentation and with/without nitrification were represented. Soluble organic
      matter was produced from all types of sludge, but the yield was to a large extent
      dependent on what type of sludge was hydrolysed. Activated sludge from wastewater
      treatment plants without pre-treatment returned more soluble carbon after
      hydrolysis than sludge from treatment plants with pre-sedimentation. In addition,
      more soluble carbon was formed from non-nitrifying activated sludge than from
      nitrifying sludge. Moreover, the maximum yield of soluble COD at 10 degrees C was
      less than the yield at 20 degrees C. The initial hydrolysis rate was found to be
      between 0.35 and 1.8 mg soluble COD/(g VS x h). With the exception of one case,
      between 15 and 50% of the produced soluble COD was shown to be volatile fatty
      acids, a suitable carbon source for biological phosphorus removal. Nitrification
      rate measurements indicated that the viability of the activated sludge was not
      affected by the hydrolysis.

PMID- 16889241
TI  - Hydrolysis and fermentation of activated sludge to enhance biological phosphorus
      removal.
AB  - The conventional mainstream enhanced biological phosphorus removal (EBPR) process
      depends on the quality of the raw incoming wastewater. An alternative sidestream
      EBPR process is presented, where the substrates for storage by the polyphosphate
      accumulating organisms (PAOs) instead come from hydrolysis of the return
      activated sludge. This process is studied in full-scale at two treatment plants
      and quantified by means of phosphorus release rates and readily biodegradable COD
      (RBCOD) accumulation rates. It was seen that not only was a significant amount of
      RBCOD stored by PAOs but an approximately equal amount was accumulated in the
      sidestream hydrolysis tank and made available for the subsequent nitrogen removal
      process. The phosphorus release of the sludge with and without addition of
      different substrates was furthermore studied in laboratory scale. The study
      showed that the process is promising and in a number of cases will have
      significant advantages compared with the conventional mainstream EBPR

PMID- 16889242
TI  - Integrated chemical--physical processes kinetic modelling of multiple mineral
      precipitation problems.
AB  - A three-phase (aqueous/gas/solid) mixed weak acid/base chemistry kinetic model is
      applied to evaluate the processes operative in the aeration treatment of swine
      wastewater (SWW) and sewage sludge anaerobic digester liquor (ADL). In both
      applications, with a single set of constants (except for the aeration rates which
      are situation specific), close correlation could be obtained between predicted
      and measured data, except for the Ca concentration-time profile in the SWW. For
      this wastewater, the model application highlighted an inconsistency in the
      measured Ca data which could not be resolved; this illustrates the value of a
      mass balance-based model in evaluating experimental data. From the model
      applications, in both wastewaters the dominant minerals precipitating are
      struvite and amorphous calcium phosphate (ACP), which precipitate simultaneously
      competing for the same species, P. The absolute and relative masses of the two
      precipitants are governed by the initial solution state (e.g. total inorganic C
      (C(T)), Mg, Ca and P concentrations), their relative precipitation rates
      (struvite > ACP) and the system conditions imposed (aeration rates and time
      applied). It is concluded that the kinetic model is able to predict correctly the
      time-dependent weak acid/base chemistry reactions and final equilibrium state for
      situations where multiple minerals competing for the same species precipitate
      simultaneously or sequentially, a deficiency in traditional equilibrium chemistry
      based algebraic models.

PMID- 16889243
TI  - Fixed film phosphorus removal--flexible enough?
AB  - While biological phosphorus removal (BPR) has been practised for 30 years, up to
      recently it has been restricted mainly to activated sludge processes, with the
      corresponding need for large basin volumes. Yet, research with biofilm reactors
      showed that the principle of alternate anaerobic and aerated conditions was
      applicable to fixed bacteria by changing the conditions in time rather than in
      space. Attached growth enhanced biological phosphorus removal (EBPR) systems are
      attractive because of their compactness and capability to retain high biomass
      levels. However, the phosphorus extraction depends on backwashes to enhance the
      phosphorus-rich attached biomass, and correct control of unsteady effluent
      quality created by frequently modified process conditions. Accordingly, EBPR
      remains a challenging task in terms of combining nitrogen and phosphorus removal
      using attached growth systems. Nevertheless, a combination of activated sludge
      and biofilm carriers, in the integrated fixed-film activated sludge system,
      provides treatment opportunities not readily available using suspended growth
      systems. Current practice is only at the beginning of exploiting the full
      potential of this combination, but the first full-scale results show that compact
      tankage and low nutrient results based on biological principles are possible.

PMID- 16889244
TI  - 10 years of operation of an integrated nutrient removal treatment plant: ups and
      downs. Background and water treatment.
AB  - Water retention times less than 3 h from inlet to outlet were necessary to meet
      new effluent requirements without extending the footprint of the existing plant.
      Nitrogen removal was required at the existing, high loaded, direct precipitation
      plant and space was not readily available. The staff at the VEAS WWTP took on the
      task to design a new process at their own risk. Selected solutions and ups and
      downs in the water treatment during the past 10 years of operations and further
      developments are presented in this paper. Always asking for well-proven solutions
      might make life easy. The intent of this paper is to encourage some of our
      colleagues to be more daring in their approach to new challenges. However, expect
      sleepless nights in order to solve the unexpected problems along the way.

PMID- 16889245
TI  - Simultaneous biological removal of sulphide and nitrate by autotrophic
      denitrification in an activated sludge system.
AB  - The feasibility of an autotrophic denitrification process in an activated sludge
      reactor, using sulphide as the electron donor, was tested for simultaneous
      denitrification and sulphide removal. The reactor was operated at nitrate (N) to
      sulphide (S) ratios between 0.5 and 0.9 to evaluate their effect on the N-removal
      efficiency, the S-removal efficiency and the product formation during anoxic
      oxidation of sulphide. One hundred per cent removal of both nitrate and sulphide
      was achieved at a NLR of 7.96 mmol N-L(-1) x d(-1) (111.44 mg NO3- -N x L(-1) x
      d(-1)) and at a N/S ratio of 0.89 with complete oxidation of sulphide to
      sulphate. The oxygen level in the reactor (10%) was found to influence the N
      removal efficiency by inhibiting the denitrification process. Moreover, chemical
      (or biological) oxidation of sulphide with oxygen occurred, resulting in a loss
      of the electron donor. FISH analysis was carried out to study the microbial
      population in the system.

PMID- 16889246
TI  - A novel process for organic acids and nutrient recovery from municipal wastewater
      sludge.
AB  - In this paper, a novel process for organic acids and nutrient recovery from
      municipal sludge was introduced and evaluated based on laboratory-scale studies.
      An economical estimation for its practical application was also performed by mass
      balance in a full-scale plant (Q=158,000 m3 d(-1)). This novel process comprises
      an upflow sludge blanket-type high performance elutriated acid fermenter (5d of
      SRT) for organic acids recovery followed by an upflow-type crystallisation (3 h
      of HRT) reactor using waste lime for nutrient recovery. In the system, the
      fermenter is characterised by thermophilic (55 degrees C) and alkaline conditions
      (pH 9), contributing to higher hydrolysis/acidogenesis (0.18 g VFA(COD) g(-1)
      VSS(COD), 63.3% of VFA(COD)/COD produced, based on sludge characteristics of the
      rainy season) and pathogen-free stabilised sludge production. It also provides
      the optimal condition for the following crystallisation reactor. In the process,
      the waste lime, which is an industrial waste, can be used for pH control and
      cation (Ca and Mg) sources for crystallisation reaction. A cost estimation for
      full-scale application demonstrates that this process has economic benefits
      (about 67 dollars per m3 of wastewater except for the energy expense) even in the
      rainy season.

PMID- 16889247
TI  - Modelling and evaluation of nitrogen removal performance in subsurface flow and
      free water surface constructed wetlands.
AB  - With the aim of protecting drinking water sources in rural regions, pilot-scale
      subsurface water flow (SSF) and free water surface flow (FWS) constructed wetland
      systems were evaluated for removal efficiencies of nitrogenous pollutants in
      tertiary stage treated wastewaters (effluent from the Pasakoy biological nutrient
      removal plant). Five different hydraulic application rates and emergent (Canna,
      Cyperus, Typhia sp., Phragmites sp., Juncus, Poaceae, Paspalum and Iris) and
      floating (Pistia, Salvina and Lemna) plant species were assayed. The average
      annual NH4-N, NO3-N and organic-N treatment efficiencies were 81, 40 and 74% in
      SSFs and 76, 59 and 75% in FWSs, respectively. Two types of the models (first
      order plug flow and multiple regression) were tried to estimate the system
      performances. Nitrification, denitrification and ammonification rate constants
      (k20) values in SSF and FWS systems were 0.898 d-1 and 0.541 d(-1), 0.486 d(-1)
      and 0.502 d(-1), 0.986 d(-1) and 0.908, respectively. Results show that the first
      order plug flow model clearly estimates slightly higher or lower values than
      observed when compared with the other model.

PMID- 16889248
TI  - Solved upscaling problems for implementing deammonification of rejection water.
AB  - So far, extremely efficient metabolic pathways for nitrogen removal exclusively
      by autotrophic organisms are well established in scientific literature but not in
      practice. This paper presents results from the successful implementation of
      rejection water deammonification in a full-scale single sludge system at the WWTP
      Strass, Austria. Anaerobic ammonia oxidising biomass has been accumulated during
      a 2.5 year start-up period when the reactor size was gradually scaled up in the
      steps. The pH-controlled deammonification system (DEMON) has reached a design
      capacity of eliminating approximately 300 kg of nitrogen per day. Energy savings
      outperform expectations, decreasing the mean specific demand for compressed air
      from 109 m3(kg N)(-1) to 29 m3(kg N)(-1). Dominance of autotrophic metabolism is
      confirmed by organic effluent loads topping influent loads.

PMID- 16889249
TI  - Autotrophic nitrogen removal from anaerobic supernatant of Florence's WWTP
      digesters.
AB  - In municipal WWTP with anaerobic sludge digestion, 10-20% of total nitrogen load
      comes from the return supernatant produced by the final sludge dewatering. In
      recent years a completely autotrophic nitrogen removal process based on Anammox
      biomass has been tested in a few European countries, in order to treat anaerobic
      supernatant and to increase the COD/N ratio in municipal wastewater. This work
      reports the experimental results of the SHARON-ANAMMOX process application to
      anaerobic supernatant taken from the urban Florentine area wastewater treatment
      plant (S. Colombano WWTP). A nitritation labscale chemostat (7.4 L) has been
      started-up seeded with the S. Colombano WWTP nitrifying activated sludge. During
      the experimental period, nitrite oxidising bacteria wash-out was steadily
      achieved with a retention time ranging from 1 to 1.5 d at 35 degrees C. The
      Anammox inoculum sludge was taken from a pilot plant at EAWAG (Zurich). Anammox
      biomass has been enriched at 33 degrees C with anaerobic supernatant diluted with
      sodium nitrite solution until reaching a maximum specific nitrogen removal rate
      of 0.065 kgN kg(-1) VSS d(-1), which was 11 times higher than the one found in
      inoculum sludge (0.005 kgN kg(-1) VSS d(-1). In a lab-scale SBR reactor (4 L),
      coupled with nitritation bioreactor, specific nitrogen removal rate (doubling
      time equal to 26 d at 35 degrees C and at nitrite-limiting condition) reached the
      value of 0.22 kgN kg(-1) VSS d(-1), which was approximately 44 times larger than
      the rate measured in the inoculum Anammox sludge.

PMID- 16889250
TI  - Disc filtration for separation of flocs from a moving bed bio-film reactor.
AB  - A Discfilter with 10 and 18 microm filter openings, respectively, was placed in
      parallel to a flotation plant for separation of biological flocs from a post
      denitrifying Kaldnes Moving Bed Process, the last treatment step at the municipal
      wastewater treatment plant at Sjounda, Malmo, Sweden. The effluent concentrations
      from the 10 and 18 microm filter were 2-5 and 2-8 mg SS L(-1), respectively,
      which is comparable to, or better than, the flotation plant. Comparison with
      experiences from activated sludge plants shows that the Discfilter works
      especially well after the Kaldnes process. Particle size distribution (PSD)
      studies show that particles larger than the filter openings of 10 and 18 microm
      are separated with approximately 90% efficiency, whereas most of the smaller
      particles pass the filter. This fact indicates that the major particle separation
      mechanism is physical blocking. These findings point to the possibility of
      improving the prediction of the separation efficiency by combining measurements
      of turbidity and suspended solids with particle size analysis.

PMID- 16889251
TI  - Combined partial nitritation/Anammox system for treatment of digester
      supernatant.
AB  - One-year (2004) comprehensive investigations in a semi-industrial pilot plant (5
      m3) were carried out with the aim of assessing the influence of operational
      parameters on the partial nitritation/Anammox system performance. In the system
      designed as a moving-bed biofilm reactor, the influent nitrogen load to the
      Anammox reactor was progressively increased and a stable Anammox bacterial
      culture was obtained. Interaction between subsequent aerobic and anaerobic
      conditions in the partial nitritation and Anammox reactors, respectively, granted
      conditions to remove nitrogen through the nitrite route. It implies that the
      oxygen supply can be limited to a high extent. A control strategy for the partial
      nitritation step relied on concomitant adjustment of the air supply with a
      variable influent nitrogen load, which can be monitored by both pH and
      conductivity measurements. In the Anammox reactor, an influent nitrite-to
      ammonium ratio plays a vital role in obtaining efficient nitrogen removal. During
      the 1-year experimental period, the Anammox reactor was operated steadily and
      average nitrogen removal efficiency was 84% with 97% as the maximum value.

PMID- 16889252
TI  - Application of a fuzzy algorithm for pH control in a struvite crystallisation
      reactor.
AB  - A struvite crystallisation process is highly dependent on pH. To achieve a high
      phosphorus recovery as struvite it is important to have an accurate control of pH
      in the reactor. The high non-linear response of pH value makes manual pH control
      difficult. Therefore, a software based on fuzzy logic control (FLC) has been
      developed to maintain the pH at a set value in a stirred reactor to crystallise
      struvite. The FLC developed has been based on Larsen's inference. In order to
      confirm the improvement of the pH stability using FLC software, different
      experiments have been carried out with manual control of the pH value, and with
      the FLC software. It has been demonstrated that using FLC software allows a
      precise control of pH with high stability, optimises the process, and minimises
      the operator intervention.

PMID- 16889253
TI  - Phosphorus removal using novel crystallisation technology.
AB  - A soy protein manufacturing facility was faced with the challenge of reducing its
      effluent phosphorus (P) content from 20-50 mg L(-1) down to <2 mg L(-1) total P
      without increasing soluble salt levels to comply with discharge and receiving
      water requirements. A number of biological and chemical P removal technologies
      previously evaluated either failed to achieve the new standards or would have
      produced prohibitive amounts of residual sludge and unacceptably high effluent
      salt concentrations. Lime precipitation, utilising a novel crystallisation
      technology, was demonstrated through on-site pilot testing to meet the process
      objectives. It is capable of achieving the required P removal at pH 10 while not
      increasing soluble salts and producing rapid settling and filterable particles.
      Also, minimal carbonate removal was observed with residual solids generation
      being only 40% of a complete lime softening reaction. This paper describes the
      technical evaluation that led to the full-scale treatment system that was put
      into operation in late 2005.

PMID- 16889255
TI  - Uncertainties of spectral in situ measurements in wastewater using different
      calibration approaches.
AB  - Three calibration methods were applied to UV/VIS spectra recorded in the influent
      of six wastewater treatment plants (WWTPs) to measure total COD (CODtot),
      filtered COD (CODfil), nitrate and nitrite nitrogen (NO(x)-N) and total suspended
      solids (TSS). It could be shown that a calibration of the sensor using data sets
      from four Swiss WWTPs leads to an improvement of the precision in comparison to
      the global calibration provided by the manufacturer. A calibration to the
      specific wastewater matrix always improves the results and gives the highest
      accuracy. For CODtot a mean coefficient of variation CVx of 12.5% could be
      reached, whereas for NOx-N only weak results were achieved (average CVx = 36%).

PMID- 16889254
TI  - Anaerobic co-digestion of sludge with other organic wastes and phosphorus
      reclamation in wastewater treatment plants for biological nutrients removal.
AB  - This paper deals with the performances obtained in full scale anaerobic digesters
      co-digesting waste activated sludge from biological nutrients removal wastewater
      treatment plants, together with different types of organic wastes (solid and
      liquid). Results showed that the biogas production can be increased from 4000 to
      some 18,000 m3 per month when treating some 3-5 tons per day of organic municipal
      solid waste together with waste activated sludge. On the other hand, the specific
      biogas production was improved, passing from 0.3 to 0.5 m3 per kgVS fed the
      reactor, when treating liquid effluents from cheese factories. The addition of
      the co-substrates gave minimal increases in the organic loading rate while the
      hydraulic retention time remained constant. Further, the potentiality of the
      struvite crystallisation process for treating anaerobic supernatant rich in
      nitrogen and phosphorus was studied: 80% removal of phosphorus was observed in
      all the tested conditions. In conclusion, a possible layout is proposed for
      designing or upgrading wastewater treatment plants for biological nutrients
      removal process.

PMID- 16889256
TI  - Calibration and simulation of ASM2d at different temperatures in a phosphorus
      removal pilot plant.
AB  - In this work, an organic and nutrient removal pilot plant was used to study the
      temperature influence on phosphorus accumulating organisms. Three experiments
      were carried out at 13, 20 and 24.5 degrees C, achieving a high phosphorus
      removal percentage in all cases. The ASM2d model was calibrated at 13 and 20
      degrees C and the Arrhenius equation constant was obtained for phosphorus removal
      processes showing that the temperature influences on the biological phosphorus
      removal subprocesses in a different degree. The 24.5 degrees C experiment was
      simulated using the model parameters obtained by means of the Arrhenius equation.
      The simulation results for the three experiments showed good correspondence with
      the experimental data, demonstrating that the model and the calibrated parameters
      were able to predict the pilot plant behaviour.

PMID- 16889257
TI  - Potential of activated sludge disintegration.
AB  - The disposal of sewage sludge and the agricultural use of stabilised sludge are
      decreasing due to more stringent regulations in Europe. An increasing fraction of
      sewage sludge must therefore be dewatered, dried, incinerated and the ashes
      disposed of in landfills. These processes are cost-intensive and also lead to the
      loss of valuable phosphate resources incorporated in the sludge ash. The
      implementation of processes that could reduce excess sludge production and
      recycle phosphate is therefore recommended. Disintegration of biological sludge
      by mechanical, thermal and physical methods could significantly reduce excess
      sludge production, improve the settling properties of the sludge and reduce
      bulking and scumming. The solubilised COD could also improve denitrification if
      the treated sludge is recycled to the anoxic zone. However, disintegration partly
      inhibits and kills nitrifiers and could therefore shorten their effective solid
      retention time, thus reducing the safety of the nitrification. This paper
      discusses the potential of disintegration on sludge reduction, the operating
      stability of nitrification, the improvement of denitrification and also presents
      an energy and cost evaluation.

PMID- 16889258
TI  - Operation of a new sewage treatment process with technologies of excess sludge
      reduction and phosphorus recovery.
AB  - This paper shows the potential application of a new sewage treatment process with
      technologies of excess sludge reduction and phosphorus recovery. The process
      incorporated ozonation for excess sludge reduction and crystallisation process
      for phosphorus recovery to a conventional anaerobic/oxic (A/O) phosphorus removal
      process. A lab-scale continuous operation experiment was conducted with the ratio
      of sludge flow rate to ozonation tank of 1.1% of sewage inflow under 30 to 40
      mgO3/gSS of ozone consumption and with sludge wasting ratio of 0.34% (one-fifth
      of a conventional A/O process). Throughout the operational experiment, a 60%
      reduction of excess sludge production was achieved in the new process. A biomass
      concentration of 2300 mg/L was maintained, and the accumulation of inactive
      biomass was not observed. The new process was estimated to give a phosphorus
      recovery degree of more than 70% as an advantage of excess sludge reduction. The
      slight increase in effluent COD was observed, but the process performance was
      maintained at a satisfactory level. These facts demonstrate an effectiveness of
      the new process for excess sludge reduction as well as for phosphorus recovery.

PMID- 16889259
TI  - Disintegration of excess activated sludge--evaluation and experience of full
      scale applications.
AB  - Anaerobic digestion of sewage sludge can be improved by introducing a
      disintegration of excess activated sludge as a pretreatment process. The
      disintegration brings a deeper degradation of organic matter and less amount of
      output sludge for disposal, a higher production of biogas and consequently energy
      yield, in some cases suppression of digesters foaming and better dewaterability.
      The full-scale application of disintegration by a lysate-thickening centrifuge
      was monitored long term in three different WWTPs. The evaluation of contribution
      of disintegration to biogas production and digested sludge quality was assessed
      and operational experience is discussed. Increment of specific biogas production
      was evaluated in the range of 15-26%, organic matter in digested sludge
      significantly decreased to 48-49%. Results proved that the installation of a
      disintegrating centrifuge in WWTPs of different sizes and conditions would be
      useful and beneficial.

PMID- 16889260
TI  - Evolution of an ASM2d-like model structure due to operational changes of an SBR
      process.
AB  - To model biological nitrogen and phosphorus removal systems with an affordable
      complexity, the ASM2d model structure is based on many assumptions. In this
      study, some of these assumptions, however, were observed to become invalid when
      the biological behaviour in the system altered in response to changes in the
      operation of the system, a pilot-scale N and P removing SBR. Particularly, the
      three applied operational scenarios resulted in three distinctive responses in
      the SBR, namely pronounced limitation of the hydrolysis of the organic nitrogen,
      nitrite build-up during aerobic conditions and also nitrite build-up during
      anoxic conditions. This shows that even for the same system with the same
      influent wastewater composition, the model structure of the ASM2d does not remain
      constant but adapts parallel to dynamic changes in the activated sludge
      community. On the other hand, the three calibrated ASM2d models still lacked the
      ability to entirely describe the observed dynamics particularly those dealing
      with the phosphorus dynamics and hydrolysis. Understanding the underlying reasons
      of this discrepancy is a challenging task, which is expected to improve the
      modelling of bio-P removing activated sludge systems.

PMID- 16889261
TI  - ASM1 dynamic calibration and long-term validation for an intermittently aerated
      WWTP.
AB  - Activated sludge models, and ASM1 in particular, are well recognised and useful
      mathematical representations of the macroscopic processes involved in the
      biological degradation of the pollution carried by wastewater. Nevertheless, the
      use of these models through simulation software requires a careful methodology
      for their calibration (determination of the model parameters' values) and the
      validation step (verification with an independent data set). This paper presents
      the methodology and the results of dynamic calibration and validation tasks as a
      prior work to a modelling project for defining a reference guideline destined to
      French designers and operators. To reach these goals, a biological nutrient
      removal (BNR) wastewater treatment plant (WWTP) with intermittent aeration was
      selected and monitored for 2 years. Two sets of calibrated parameters are given
      and discussed. The results of the long-term validation task are presented through
      a 2-month simulation with lots of operation changes. Finally, it is concluded
      that, even if calibrating ASM1 with a high degree of confidence with a single set
      of parameters was not possible, the results of the calibration are sufficient to
      obtain satisfactory results over long-term dynamic simulation. However,
      simulating long periods reveals specific calibration issues such as the variation
      of the nitrification capacity due to external events.

PMID- 16889262
TI  - Computational fluid dynamics modelling of hydraulics and sedimentation in process
      reactors during aeration tank settling.
AB  - Aeration tank settling is a control method allowing settling in the process tank
      during high hydraulic load. The control method is patented. Aeration tank
      settling has been applied in several waste water treatment plants using the
      present design of the process tanks. Some process tank designs have shown to be
      more effective than others. To improve the design of less effective plants,
      computational fluid dynamics (CFD) modelling of hydraulics and sedimentation has
      been applied. This paper discusses the results at one particular plant
      experiencing problems with partly short-circuiting of the inlet and outlet
      causing a disruption of the sludge blanket at the outlet and thereby reducing the
      retention of sludge in the process tank. The model has allowed us to establish a
      clear picture of the problems arising at the plant during aeration tank settling.
      Secondly, several process tank design changes have been suggested and tested by
      means of computational fluid dynamics modelling. The most promising design
      changes have been found and reported.

PMID- 16889263
TI  - Anammox process for nitrogen removal from anaerobically digested fish canning
      effluents.
AB  - The Anammox process was used to treat the effluent generated in an anaerobic
      digester which treated the wastewater from a fish cannery once previously
      processed in a Sharon reactor. The effluents generated from the anaerobic
      digestion are characterised by their high ammonium content (700-1000 g NH4+ -Nm(
      3)), organic carbon content (1000-1300 g TOCm(-3)) and salinity up to 8,000
      10,000 g NaCl m(-3). In the Sharon reactor, approximately 50% of the NH4+ -N was
      oxidised to NO2- -N via partial nitrification. The effluent of the Sharon step
      was fed to the Anammox reactor which treated an averaged nitrogen loading rate of
      500 g N m(-3) x d(-1). The system reached an averaged nitrogen removal efficiency
      of 68%, mainly limited due to the nonstoichiometric relation, for the Anammox
      process, between the ammonium and nitrite added in the feeding. The Anammox
      reactor bacterial population distribution, followed by FISH analysis and batch
      activity assays, did not change significantly despite the continuous entrance to
      the system of aerobic ammonium oxidisers coming from the Sharon reactor. Most of
      the bacteria corresponded to the Anammox population and the rest with slight
      variable shares to the ammonia oxidisers. The Anammox reactor showed an
      unexpected robustness despite the continuous variations in the influent
      composition regarding ammonium and nitrite concentrations. Only in the period
      when NO2- -N concentration was higher than the NH4+ -N concentration did the
      process destabilise and it took 14 days until the nitrogen removal percentage
      decreased to 34% with concentrations in the effluent of 340g NH4+ -N m(-3) and
      440 g NO2- -N m(-3), respectively. Based on these results, it seems that the
      Sharon-Anammox system can be applied for the treatment of industrial wastewaters
      with high nitrogen load and salt concentration with an appropriate control of the
      NO2- -N/NH4+ -N ratio.

PMID- 16889265
TI  - Effect of inorganic carbon on nitrite accumulation in an aerobic granule reactor.
AB  - Pilot scale experiments were performed to evaluate the potential of nitrite type
      nitrification process with an airlift reactor and granular biomass. Initially,
      oxygen limitation was used as the main control parameter for accumulating nitrite
      in the effluent. After 30 d operation, the maximum nitrite conversion rate
      reached 2.5 kgNO2-N m(-3) d(-1), average diameter of the granule was 0.7 mm.
      Nitrite type reaction continued over 100 d, but nitrate formation increased after
      150 d of operation. Once nitrate formation increased, oxygen limitation could not
      eliminate nitrite oxidising bacteria from granule. To overcome nitrate formation,
      laboratory scale batch experiments were conducted and it revealed a high
      concentration of inorganic carbon which had a significant effect on nitrite
      accumulation. Following this new concept, inorganic carbon was fed to the pilot
      scale reactor by changing pH adjustment reagent from NaOH to Na2CO3 and nitrite
      accumulation was recovered successfully without changing DO concentration. These
      results show that a high concentration of inorganic carbon is one of the control
      parameters for accumulating nitrite in biofilm nitrification system.

PMID- 16889264
TI  - Performance evaluation of SBR treatment for nitrogen removal from tannery
      wastewater.
AB  - Performance of SBR treatment for nitrogen removal from tannery is evaluated for a
      wide range of wastewater temperature between 7 and 30 degrees C. A pilot-scale
      SBR unit fed with plain-settled wastewater is operated on site for this purpose.
      Effective nitrogen removal is sustained by adjustment of the sludge age from 28
      to 5 days. Concentration profiles of nitrogen compounds within a selected
      complete SBR cycle during the steady state operation at different wastewater
      temperatures and sludge ages are evaluated by model simulation. System
      performance is also interpreted in terms of modeling and stoichiometric
      calculation. Additional nitrate loss was observed during aerobic period when the
      aeration intensity was reduced by the factor of 50%.

PMID- 16889266
TI  - A comparison of BNR activated sludge systems with membrane and settling tank
      solid-liquid separation.
AB  - Installing membranes for solid-liquid separation into biological nutrient removal
      (BNR) activated sludge (AS) systems makes a profound difference not only to the
      design of the membrane bio-reactor (MBR) BNR system itself, but also to the
      design approach for the whole wastewater treatment plant (WWTP). In multi-zone
      BNR systems with membranes in the aerobic reactor and fixed volumes for the
      anaerobic, anoxic and aerobic zones (i.e. fixed volume fractions), the mass
      fractions can be controlled (within a range) with the inter-reactor recycle
      ratios. This zone mass fraction flexibility is a significant advantage of MBR BNR
      systems over BNR systems with secondary settling tanks (SSTs), because it allows
      changing the mass fractions to optimise biological N and P removal in conformity
      with influent wastewater characteristics and the effluent N and P concentrations
      required. For PWWF/ADWF ratios (fq) in the upper range (fq approximately 2.0),
      aerobic mass fractions in the lower range (f(maer) < 0.60) and high (usually raw)
      wastewater strengths, the indicated mode of operation of MBR BNR systems is as
      extended aeration WWTPs (no primary settling and long sludge age). However, the
      volume reduction compared with equivalent BNR systems with SSTs will not be large
      (40-60%), but the cost of the membranes can be offset against sludge thickening
      and stabilisation costs. Moving from a flow unbalanced raw wastewater system to a
      flow balanced (fq = 1) low (usually settled) wastewater strength system can
      double the ADWF capacity of the biological reactor, but the design approach of
      the WWTP changes away from extended aeration to include primary sludge
      stabilisation. The cost of primary sludge treatment then has to be offset against
      the savings of the increased WWTP capacity.

PMID- 16889267
TI  - Nitrogen recovery by urea hydrolysis and struvite precipitation from
      anthropogenic urine.
AB  - Human urine is a source of nutrients and has a significant potential for recycle
      of nitrogen. Recently, much research focused on separate collection and treatment
      of human urine. Recovery of nutrients from human urine requires hydrolysis of
      urea into ammonia and subsequent removal of ammonia and sometimes phosphorus.
      This study attempted to evaluate urea hydrolysis of human urine in both untreated
      fresh samples and urease added urine samples. Recovery of nutrients by struvite
      precipitation on pre-hydrolysed samples was also assessed on undiluted and 1:1
      diluted samples. Results of urea hydrolysis on untreated urine samples indicated
      that the process was slow and pH exerted a significant effect on the process. No
      hydrolysis occurred above pH 10. From pH 2 to 7.5, 25% of urea could be
      hydrolysed in 30 d. Urease added hydrolysis with the enzyme doses 25-49 mg L(-1)
      was a rapid process providing complete conversion into ammonia in 1.5 h. Struvite
      precipitation conducted on enzyme hydrolysed urine sample proved to be an
      efficient process and ammonia removals up to 95% were obtained. Struvite
      precipitation also provided 50% organic nitrogen removal.

PMID- 16889268
TI  - Sensitivity analysis of a biofilm model describing mixed growth of nitrite
      oxidisers in a CSTR.
AB  - A simple kinetic model has been developed for describing nitrite oxidation by
      autotrophic aerobic nitrifiers in a CSTR reactor, in which mixed (suspended and
      attached) growth conditions are prevailing. In this work, a critical
      dimensionless parameter is identified containing both biofilm characteristics and
      microbial kinetic parameters, as well as the specific (per volume) surface of the
      reactor configuration used. Evaluation of this dimensionless parameter can easily
      provide information on whether or not wall attachment is critical, and should be
      taken into account either in kinetic studies or in reactor design, when specific
      pollutants are to be removed from the waste influent stream. The effect of bulk
      dissolved oxygen (DO) concentration on the validity of this model is addressed
      and minimum non-limiting DO concentrations are proposed depending on the reactor
      configuration.

PMID- 16889269
TI  - An innovative technology based on aerobic granular biomass for treating municipal
      and/or industrial wastewater with low environmental impact.
AB  - The paper reports the results of an investigation carried out at lab scale to
      assess the effectiveness of an innovative technology (SUPERBIO) for treating
      municipal and/or industrial wastewater. When this technology was applied for
      treating municipal wastewater, the results showed that even at maximum organic
      load (i.e. 7 kg COD m(-3) d(-1)), the COD in the treated effluent was lower than
      50 mg L(-1). In addition, both ammonia and TKN removal efficiencies resulted in
      higher than 87% up to an organic load of 5.7 kg COD m(-3) d(-1) corresponding to
      a nitrogen load of 0.8 kg TKN m(-3) d(-1). Very satisfactory process performances
      also resulted during tannery wastewater treatment, when a chemical oxidation step
      (i.e. ozonation) was inserted in the treatment cycle of SUPERBIO. In such an
      instance, at organic and nitrogen loadings of 3 kgCOD m(-3) d(-1) and 0.20 kg N
      m(-3) d(-1), COD, NH4+ -N and TSS average removals were 96, 99 and 98%,
      respectively. Finally, during the whole experimentation, SUPERBIO was always
      characterised by a very low sludge production. Such a result was ascribed mainly
      to the characteristics of biomass that grew in the form of very dense granules
      (i.e. 130 gVSS L(Biomass)(-1) allowing a biomass concentration as high as 50-60
      gTSS l(bed)(-1) to be achieved.

PMID- 16889270
TI  - Specialist trusts lobby ministers for change in tarriff.

PMID- 16889271
TI  - Reconfiguration. Herts and minds: 100 m pound hole that could defeat protesters.

PMID- 16889272
TI  - On effective health messages.

PMID- 16889273
TI  - Consultant clinical activity is key to improving productivity.

PMID- 16889274
TI  - Barometer. PCTS June 2006.

PMID- 16889275
TI  - Staying Power.
AB  - A U.S. firm's pioneering approach to healthcare for older patients has produced
      lower admission rates and shorter stays than equivalent care in the NHS. The
      firm's approach involves closer integration between primary and secondary care.
      Pilot sites in the U.K. show the importance of integration across sectors and
      into the community.

PMID- 16889276
TI  - On public health.

PMID- 16889277
TI  - Social care. A champion for change.

PMID- 16889278
TI  - Adherence to treatment: assessment of an unmet need in asthma.
AB  - BACKGROUND: In asthma, as in other chronic conditions, poor adherence to
      treatment and to medical advice is common and contributes to substantial
      worsening of the disease and increased health care costs. OBJECTIVE: The aim of
      the present study was to evaluate patients' self-reported adherence to asthma
      medication regimens and to identify possible correlations between treatment
      adherence and depression, anxiety, and coping strategies. METHODS: Sixty-three
      asthmatic outpatients (27 men and 36 women; mean age +/- SD, 38.5 +/- 14.1) were
      consecutively enrolled during their routine control visit. Patients were asked to
      complete 3 different questionnaires: the Adherence Schedule in Asthma, the
      Hospital Anxiety and Depression Scale, and the Coping Orientations to Problem
      Experienced questionnaires. RESULTS: Depression was detected in 32.3% of patients
      and anxiety in 34.9%. A negative correlation was found between older age and
      perception of family support (rho = -0.33). The presence of anxiety displayed a
      positive correlation with difficulty in accepting the illness (rho = 0.33) and a
      negative correlation with acceptance of illness limitations (p = -0.30); it was
      also positively correlated with fear of the side effects of medication (rho =
      0.37). The presence of depression was negatively correlated with acceptance of
      illness limitations (rho = -0.32), knowledge of the illness (p = -0.29), and with
      ability to identify worsening signs (rho = -0.31). CONCLUSION: This study shows
      how different factors may modulate adherence to asthma treatment. The opportunity
      to identify reasons for nonadherence through a simple assessment will allow a
      tailored intervention to be planned for each patient.

PMID- 16889279
TI  - Hymenoptera venom immunotherapy and field stings.
AB  - BACKGROUND: Anaphylactic sting reactions in patients with Hymenoptera venom
      allergy are prevented by venom immunotherapy (VIT) in most patients. OBJECTIVE:
      The aim of this study was to investigate re-sting reactions in the field during
      VIT or during an observation period of up to 13 years after cessation of
      treatment. Furthermore we sought to identify patients at higher risk of
      developing a systemic allergic reaction (SAR) and to assess possible correlations
      with basal serum tryptase concentration. METHODS: The clinical data of 192
      patients with a recorded field sting during VIT were evaluated and the patients
      were questioned regarding possible re-stings after cessation of VIT. Baseline
      mast-cell tryptase concentrations and specific IgE were analyzed in patients with
      a reported SAR. RESULTS: Of 192 patients with reported re-stings in the field, 27
      developed SARs (14.1%). A SAR occurred in 11.9% of the stings delivered during
      VIT, whereas 9.7% of the stings resulted in a SAR after VIT. The majority of SARs
      in response to a field sting during VIT were mild, whereas severe SARs occurred
      more often after VIT and repeated reexposure. Out of 23 patients with reported
      SARs, 2 (8.7%) had elevated basal serum tryptase. CONCLUSIONS: VIT lasting for at
      least 3 years is effective in protecting the vast majority of patients. The
      individual predictability of the response of patients to a field sting is low.
      SARs of increased severity mainly occur after therapy and after tolerating
      consecutive stings.

PMID- 16889280
TI  - Rush hymenoptera venom immunotherapy is efficacious and safe.
AB  - BACKGROUND: Although rapid venom immunotherapy (VIT) protocols have been shown to
      be safe and effective, this issue has not yet been clarified in Turkey.
      OBJECTIVE: The aim of this study was to evaluate the side effects of rush VIT as
      well as early clinical and immunological responses in patients with a venom
      allergy. METHODS: Eighteen patients who had a history of severe systemic
      reactions after Hymenoptera sting were included in the study. The diagnosis was
      made on the basis of positive skin test reactivity and the presence of specific
      IgE in serum to either bee or vespid venoms. Fourteen patients underwent an
      average 7-day rush VIT regimen under careful monitoring in our clinic. Among them
      7 patients were treated with Vespula species and 7 with Apis mellifera venom
      extracts. Four patients were followed up as a control group. Skin test response,
      specific IgE and IgG4 levels were determined before and after a year of VIT.
      Local and systemic reactions due to injections were monitored during the
      induction and maintenance phases of VIT. RESULTS: Specific IgG4 levels
      significantly increased after 1 year compared with levels before VIT (mean
      concentration before and after; 13.04 vs 21.85 mg/L, respectively; P < .05)
      whereas specific IgE levels did not change (11.54 vs. 13.32 kU/L). No significant
      differences were observed before and after one year of VIT in skin prick (2.34 vs
      3.66 mm) and intradermal (0.12-0.11 microg/mL) test reactivities (P > .05). A
      single patient treated with bee venom developed 4 mild systemic reactions (4/469
      injections, 0.85%) during the course of VIT. More local reactions occurred in
      patients receiving bee venom extract (3.33%) than in those receiving yellow
      jacket venom (1.33%). Two patients tolerated field stings without reactions.
      CONCLUSION: Our experience confirms that rush VIT is safe and has a low systemic
      reaction. It can be considered for patients requiring rapid protection.

PMID- 16889282
TI  - A Mexican population-based study on exposure to paracetamol and the risk of
      wheezing, rhinitis, and eeczema in childhood.
AB  - BACKGROUND: There is some evidence suggesting a link between paracetamol exposure
      and atopy in both adults and children. OBJECTIVE: We aimed to investigate whether
      further epidemiological support for a link between paracetamol intake and allergy
      could be found in a population of Mexican children. METHODS: In a cross-sectional
      study design, we applied the ISAAC questionnaire to 3493 children aged 6 to 7
      years old. Two analyses were performed: (1) children were classified as cases if
      they had wheezing, rhinitis, or eczema at any time from their neonatal period up
      until they reached the age of 6 to 7 years, or as controls if they had never
      experienced these conditions, and (2) children were classified as cases if they
      had wheezing, rhinitis, or eczema in the 12 months prior to the study.
      Paracetamol intake was considered positive if it frequently occurred during the
      first year of life (first analysis) or in the last 12 months (second analysis).
      RESULTS: Paracetamol intake in the first year of life was significantly
      associated with an increased risk of ev having wheezing (adjusted odds ratio
      [OR], 1.69; 95% confidence interval [CI], 1.23 to 2.34) and rhinitis (adjusted
      OR, 1.37; 95% CI, 1.20 to 1.59) but not eczema (adjusted OR, 1.45; 95% CI, 0.91
      to 2.32). Frequent paracetamol intake in the last year increased the risk of
      wheezing (OR, 3.3; 95% CI, 1.54 to 7.18), rhinitis (OR, 1.61; 95% CI, 1.33 to
      1.95), or eczema (OR, 1.82; 95% CI, 1.24 to 2.66). CONCLUSION: Frequent
      paracetamol exposure was associated with a significantly increased risk of
      wheezing and rhinitis and probably eczema in a Mexican population of children.

PMID- 16889281
TI  - Comparison of exhaled nitric oxide measurement with conventional tests in steroid
      naive asthma patients.
AB  - BACKGROUND: Nitric oxide (NO) is a molecule with potent biological activity that
      plays an important role in the physiology of the respiratory system. Increased
      expression of inducible nitric oxide synthase (iNOS) and elevated fractional
      concentration of exhaled nitric oxide (F(ENO)) are seen in asthmatic patients.
      Measurement of F(ENO) has become increasingly recognized for use in the
      evaluation of bronchial inflammation during monitoring of antiinflammatory
      treatment. OBJECTIVES: The aim of this study was to evaluate F(ENO) in a group of
      steroid-naive asthmatics and assess the relationship of this parameter with the
      results of other tests used in the diagnosis of asthma and monitoring of
      antiinflammatory treatment in asthmatic patients. METHODS: The study was
      conducted in a group of 101 steroid-naive asthmatics (56 allergic and 45
      nonallergic) and 39 healthy volunteers. All patients underwent measurement of
      F(ENO), skin prick tests with common inhaled allergens, analysis of serum
      eosinophil cationic protein (ECP) and blood eosinophilia, and flow-volume
      spirometry. When the forced expiratory volume in the first second (FEV1) was less
      than 80% of predicted, reversibility of airway obstruction with a beta2-agonist
      was assessed. A nonspecific bronchial provocation test with histamine was carried
      out in asthmatic patients with a baseline FEV1 of more than 70% of predicted.
      RESULTS: Compared to the healthy volunteers, F(ENO) was elevated in both groups
      of asthmatics. F(ENO) in the allergic asthma group was higher than in the group
      of nonallergic asthmatics. In allergic and nonallergic asthmatics, F(ENO) was
      significantly correlated with bronchial hyperresponsiveness to histamine,
      reversibility of airway obstruction, serum ECP levels, and blood eosinophilia.
      F(ENO) did not correlate with baseline FEV, in either group of asthmatics. In 31%
      of nonallergic and 9% of allergic patients, F(ENO) was less than 20 parts per
      billion. CONCLUSIONS: We suggest that measurement of F(ENO) could be clinically
      useful in steroid-naive asthmatics and should be more widely used in clinical
      practice. Measurement of F(ENO) is a noninvasive, simple, and reproducible
      procedure, the results of which correlate with other routinely used methods in
      the diagnosis of asthma. However, it is worth noting that some patients,
      especially those with nonallergic asthma, do not display elevated F(ENO).

PMID- 16889283
TI  - Pollen specific immunotherapy is not a risk factor for de novo sensitization to
      cross-reacting allergens in monosensitized subjects.
AB  - BACKGROUND: Some studies have suggested that specific immunotherapy (SIT) may
      cause de novo sensitization to allergenic proteins to which patients were not
      previously allergic. This event might theoretically involve cross-reacting pollen
      allergens, such as profilin or polcalcins, posing a risk of SIT-induced
      polysensitization to pollens in patients who were originally monosensitized.
      OBJECTIVES: The aim of this study was to assess whether injection SIT with
      commercial pollen extract represents a risk factor for the de novo development of
      sensitization to different pollens in monosensitized patients. METHODS: The study
      involved 142 subjects diagnosed as being monosensitized to a single pollen: 64
      patients who were administered a 3-year course of injection SIT and 78 controls.
      Subjects underwent control skin prick tests (SPT) with a series of 8 seasonal
      airborne allergens at least 3 years after the first visit. Patients with 5 or
      more new sensitivities on SPT were considered to be de novo polysensitized.
      RESULTS: At the end of the 3-year follow-up period, the proportion of
      polysensitized subjects was identical in previously monosensitized patients who
      underwent SIT and control individuals (11% and 10%, respectively). Individuals
      who were polysensitized were significantly younger than those who were not (mean
      age +/- SD, 21.6 +/- 11.0 years vs. 31.6 +/- 15.6 years; P < .05). CONCLUSION:
      SIT does not represent a risk factor for progression towards multiple pollen
      sensitization in monosensitized pollen-allergic patients.

PMID- 16889284
TI  - Anisakis simplex allergy after eating chicken meat.
AB  - BACKGROUND: Allergic reactions to food can be produced by contaminants that
      induce sensitization. Among these, Anisakis simplex can cause seafood
      infestation, and allergic symptoms (urticaria-angioedema, anaphylaxis, and
      asthma) can follow the eating or handling of affected fish. Although seafood is
      the principal source of human infections by this parasite, we have found allergic
      symptoms in 8 patients previously diagnosed as having A simplex sensitization
      after they ate chicken meat. Chicken feed usually has a high proportion of
      fishmeal, which might possibly be contaminated by this nematode. OBJECTIVE: The
      aim of our study was to determine whether parasite proteins present in chicken
      meat could be responsible for the symptoms reported by these subjects. METHODS:
      We carried out in vivo tests (prick, bronchial challenge, and double-blind
      placebo-controlled challenge with meat chicken) in these 8 patients. We performed
      immunoblotting using the sera from the 8 patients and controls in order to detect
      A simplex sensitization. We also investigated the presence of A simplex proteins
      in sera from chickens fed with fishmeal and in other sera from chickens fed only
      with cereals. We excluded sensitization to other chicken nematodes by serologic
      methods. RESULTS: All 8 patients presented positive prick and challenges to A
      simplex. When we used serum from chickens fed with fishmeal as the antigen in
      blotting, patients 3, 4, 5, 6, 7, and 8 recognized a band of 16 kd, also obtained
      when using pools of fish-shellfish and A simplex larva. No detection was observed
      with sera from chickens fed with only cereals. CONCLUSION: We provide evidence,
      based on in vivo and in vitro tests, that subjects highly sensitized to A simplex
      can detect the presence of Anisakis species allergens in chicken meat.

PMID- 16889285
TI  - Fixed exanthema from systemic tobramycin.
AB  - Eye drops contain several ophthalmic medications which can produce allergic
      reactions. We report the case of a patient with contact dermatitis from neomycin
      and a probable fixed exanthema after parenteral administration of tobramycin who
      tolerated topical tobramycin and other aminoglycosides.

PMID- 16889286
TI  - Ibuprofen-induced fever in Sjogren's syndrome.
AB  - A 68-year-old woman with a medical history significant for Sjogren syndrome and
      leukocytoclastic vasculitis of small vessels presented to the emergency
      department with chills, malaise, a temperature of 39 degrees C, nausea, vomiting,
      and hypotension. Fifteen minutes earlier she had taken ibuprofen for flu-like
      symptoms. She was treated with a perfusion of intravenous saline, paracetamol,
      and ciprofloxacin with improvement 24 hours later. Three months later, she had a
      similar episode, without hypotension. An oral challenge test with ibuprofen in
      the hospital produced the same symptoms 3 hours after the last dose. She was
      treated with metamizole and paracetamol and was asymptomatic the next day. This
      is the first report of a febrile reaction to ibuprofen in a patient with
      Sjogren's syndrome.

PMID- 16889287
TI  - Severe dapsone hypersensitivity syndrome.
AB  - Dapsone, a potent antiparasitic and anti-inflammatory compound, is mainly used in
      the treatment of leprosy and a variety of blistering skin diseases. It may cause
      a severe adverse drug reaction with multiorgan involvement known as dapsone
      hypersensitivity syndrome. We report the case of a 21-year-old female patient
      with dapsone hypersensitivity syndrome. The clinical presentation mimicked a
      viral exanthema.

PMID- 16889289
TI  - Friction points!

PMID- 16889288
TI  - Simultaneous allergy to vine pollen and grape.
AB  - We report the case of an 18-year-old female student suffering from seasonal
      rhinoconjunctivitis with sensitization to pollens from vine and also from grass,
      olive, and Chenopodiaceae plants who had recently developed episodes of itching,
      maculopapular rash, and facial angioedema after eating grapes. Testing revealed
      positive reactions to vine pollen and grapes, and specific IgE were found for
      both allergens. Immunoblotting and inhibition assays revealed cross-reactivity
      between the allergenic structures of vine pollen and grape fruit and also among
      botanically unrelated pollens.

PMID- 16889290
TI  - Knowing no boundaries: five crucial conversations for influencing administration.

PMID- 16889291
TI  - Separately together--build unity by strengthening physician groups.

PMID- 16889292
TI  - Structured dialogue between physicians and administrators yields positive
      results.

PMID- 16889293
TI  - On the firing line.

PMID- 16889294
TI  - JCAHO standards up the ante for leadership.

PMID- 16889295
TI  - Pay for performance--a clash of cultures.
AB  - Implementation of pay for performance is being widely heralded as a new paradigm.
      However, the concept is not only alien to physicians, but may be ethically
      abhorrent, as well.

PMID- 16889296
TI  - Peer review and privileging. One pill cures all--but it's tough to swallow.

PMID- 16889298
TI  - Health care whistleblower suits expected to increase.

PMID- 16889297
TI  - Patient safety checklist: keys to successful implementation.

PMID- 16889300
TI  - A seat at the power table: the physician's role on the hospital board.

PMID- 16889299
TI  - Do your people want to do what is needed?

PMID- 16889301
TI  - The key to collaboration is to accept and manage conflict.

PMID- 16889302
TI  - Trouble brews between medical staff management. If you must blame someone, blame
      Herbert Spencer.

PMID- 16889303
TI  - Funding row could see 1800 patients rejected by foundation.

PMID- 16889304
TI  - SHA chief execs. Inside the minds of the new leaders.

PMID- 16889305
TI  - On overlooking talent.

PMID- 16889306
TI  - Public procurement. Good buy to all that.

PMID- 16889307
TI  - Data briefing. Cost benchmarking for foundations.

PMID- 16889308
TI  - Mental health. Ten points for a big difference.

PMID- 16889309
TI  - Working lives. Serving to win on centre court.

PMID- 16889310
TI  - American College Health Association National College Health Assessment (ACHA
      NCHA) Spring 2005 Reference Group Data Report (Abridged).
AB  - Assessing and understanding the health needs and capacities of college students
      is paramount to creating healthy campus communities. The American College Health
      Association-National College Health Assessment (ACHA-NCHA) is a survey instrument
      developed by the ACHA in 1998 to assist institutions of higher education in
      achieving this goal. The ACHA-NCHA contains approximately 300 questions assessing
      student health status and health problems, risk and protective behaviors, access
      to health information, impediments to academic performance, and perceived norms
      across a variety of content areas (eg, injury prevention; personal safety and
      violence; alcohol, tobacco, and other drug use; sexual health; weight, nutrition,
      and exercise; mental health). Twice a year, the ACHA compiles aggregate data from
      participating institutions in a reference group report for data comparison.
      Results from the Spring 2005 Reference Group (N = 54,111) are presented in this
      article.

PMID- 16889311
TI  - Assessing the risk factors for suicidal thoughts at a nontraditional commuter
      school.
AB  - The sample of students completing the National College Health Assessment (NCHA)
      Survey at the University of Utah differs from the national reference group for
      the NCHA 2003 in age, employment, residence, and marital status. The purpose of
      this study is to determine if the defining characteristics of a commuter school
      increase the risk for suicidal thoughts. During the fall semester of 2004, the
      University of Utah implemented a randomized electronic survey assessing the
      student body's health status in several areas. The authors compared 88
      respondents who endorsed seriously considered suicide in the previous 12 months
      were with the remaining 954 respondents to identify discriminating variables.
      Those students who seriously considered suicide more likely lived off campus,
      indicated they were emotionally abused, were in only fair health, experienced
      being assaulted, experienced unwanted sexual touching, or were not heterosexual.
      Students who were employed were significantly less likely to consider suicide.

PMID- 16889312
TI  - Texas college students' opinions of no-smoking policies, secondhand smoke, and
      smoking in public places.
AB  - Abstract. The authors examined college student opinions of no-smoking policies,
      secondhand smoke, and smoking in public places. A convenience sample of 1,188
      (66.4% female; 26.9% White, 64.1% Black, and 9.0% Hispanic) students attending 5
      Texas colleges volunteered to complete a 60-item anonymous survey on tobacco
      attitudes and behaviors. Results of our study showed that women, Black students,
      and nonsmoking students reported the most favorable attitudes toward no smoking.
      Male students, white students, and students who smoked in the past 30 days
      (current smokers) reported the least favorable attitudes. The lowest level of
      agreement by all subgroups was provided for prohibiting smoking everywhere on
      campus (inside and outside of buildings). Implications for tobacco control on
      college campuses are discussed.

PMID- 16889313
TI  - Evaluation of the energize your life! Social marketing campaign pilot study to
      increase fruit intake among community college students.
AB  - In this study, the authors evaluated the effectiveness of the Energize Your Life!
      social-marketing campaign pilot study to improve knowledge, attitudes, and fruit
      intake among community college students. The authors used a cross-sectional,
      quasi-experimental, pre- and posttest design. They randomly selected community
      college students (N = 1,367) and exposed the intervention campus to fruit fairs
      to distribute fresh fruit, 100% fruit juice, and fruit smoothie samples and
      information about fruit to students. The authors also addressed policy change to
      increase the accessibility of fruit on campus. There was a significant increase
      in fruit intake between pre- and posttest at the intervention campus. Although
      students had positive attitudes toward intake, most did not achieve the minimum
      recommended daily 2 servings of fruit. Approximately 25% of the students had
      insufficient funds, which affected their food intake. Longer-term social
      marketing interventions may be an effective means of improving the dietary
      quality of community college students.

PMID- 16889314
TI  - Changes in body weight and fat mass of men and women in the first year of
      college: A study of the "freshman 15".
AB  - Students entering their first year of college are faced with many stresses and
      changes, including changes in eating and exercise behavior. A common but often
      undocumented myth among college students is that there is a high risk of gaining
      15 pounds of weight during freshman year. The objective of this study was to
      measure changes in body weight and percentage of body fat among first-year
      college students. Using a digital scale with bio-electrical impedance, the
      authors measured height, weight, and percentage of body fat for a sample of
      students who volunteered to be weighed during a health assessment in the
      university dining halls. The authors sent e-mails inviting those same students to
      complete a second measurement in February of the academic year. Sixty-seven of
      the 217 students who volunteered for the health assessment agreed to undergo a
      second set of measurements in the spring. The mean change in body weight was 2.86
      pounds (1.3 kg, SD = 4.0 kg), and the mean change in percentage of body fat was
      0.7% (SD = 4.0%). For those students who gained weight only, the mean increase in
      body weight (as measured by body mass index, weight divided by height in kg/m2)
      was 6.82 pounds (3.1 +/- 2.4 kg) and percentage of body fat was 0.9 +/- 3.8%. The
      authors found that the first year of college is a period in which weight and fat
      gain may occur. The exact causes behind these changes are unclear and warrant
      further research to plan or improve intervention and prevention.

PMID- 16889316
TI  - A view through a different lens: photovoice as a tool for student advocacy.
AB  - To complement National College Health Assessment data and to further assess
      student lives and health needs, staff at the Rutgers University Health Services'
      Department of Health Education used a participatory research method called
      photovoice. Using this methodology, health care professionals provided a discrete
      and tangible way for students to feel empowered, as the students conducted the
      project themselves, collecting data using photography, analyzing the results
      qualitatively, and meeting with policy makers to discuss their photos and offer
      recommendations for change. Policy recommendations addressed issues of safety,
      nutrition, sexual health information, alcohol and drugs, and campus parking. In
      this article, the authors offer a description of this process as another tool for
      assessment and advocacy.

PMID- 16889315
TI  - If you feed them, will they come? The use of social marketing to increase
      interest in attending a college alcohol program.
AB  - The authors used social marketing to design and test advertisement components
      aimed at increasing students' interest in attending an alcohol program focused on
      reaching students who drink heavily, although the authors offered no such
      program. Participants were undergraduate students in introductory psychology
      courses (N = 551). Questionnaires included measures assessing demographic
      information, alcohol use and negative consequences, and interest in attending an
      alcohol program in response to exposure to 1 of 12 systematically varied
      advertisements. The authors found that approximately 20% of participants across
      all ad types indicated some level of interest in attending the alcohol program.
      Students who use alcohol reported more interest in attending when an
      informational message was used. Of the participants offered food, 41.9% indicated
      the food offered in the advertisement impacted their interest in attending.
      Results suggest market segmentation plays a role in developing effective
      advertisements to recruit different groups of students based on their reported
      drinking behavior.

PMID- 16889318
TI  - The goals of palliative care: beyond symptom control.

PMID- 16889317
TI  - Goodness of fit assessment of an alcohol intervention program and the underlying
      theories of change.
AB  - The authors conducted an investigation of The Pennsylvania State University's
      Alcohol Intervention Program Level 2 (AIP2) to determine goodness of fit of the
      program components and its underpinning theories. They determined that the Health
      Belief Model, Social Norms Theory, Social Learning Theory, and the
      Transtheoretical Model Stages of Change and Process of Change are associated with
      AIP2's program elements. Although elements of AIP2 fit with these theories, gaps
      did exist within the program. The authors put forth recommendations for
      additional program elements that would strengthen the fit with these theories and
      enhance the program. In addition, upon examining the Transtheoretical Model
      Stages of Change and Process of Change in terms of sequence, the authors found
      that information from the readiness to change assessment was not being used to
      tailor the program elements to individual participant needs. Moreover, the
      postreadiness-to-change measure adapted by a prereadiness-to-change assessment
      was not useful in determining behavior change.

PMID- 16889319
TI  - The appraisal of positive life changes following cancer diagnosis: an interview
      study.
AB  - OBJECTIVE: This research examines positive life changes that cancer patients may
      experience following their diagnosis. Although cancer is often believed to have
      negative impacts on the life of patients, positive impacts have been also
      discussed empirically. This study focuses on cancer patients' appraisal of
      positive life changes following their diagnosis and examines how and in which
      fields they recognize their lives as positively changed based on the study of
      Petrie et al. (1999). METHODS: A total of eight cancer patients in a cancer
      support group participated in this research. A group discussion and
      semistructured interviews were conducted. Content analysis was applied. RESULTS:
      The content analysis produced insights into the seven types of cancer-related
      life changes: improved empathy, greater knowledge about health, renewed
      recognition of life, change in personal life priorities, greater appreciation of
      health and life, improved close relationships, and healthy lifestyle change.
      Negative life changes were also reported. SIGNIFICANCE OF THE RESEARCH: This
      research showed that cancer patients tended to find and appraise their own
      positive life changes following cancer. The categorization of positive life
      changes basically supported that of Petrie et al. (1999), but produced an
      original category: renewed recognition of life. Positive life changes might be
      seen as a natural process that encourages patients' adjustment to cancer.
      Understanding positive impacts of cancer could be important in capturing the life
      sized features of cancer patients. Future research could expand the view of the
      impacts of cancer and demonstrate how people recognize them as benefits.

PMID- 16889320
TI  - Collective soul: the spirituality of an interdisciplinary palliative care team.
AB  - OBJECTIVE: Although spirituality as it relates to patients is gaining increasing
      attention, less is known about how health care professionals (HCP) experience
      spirituality personally or collectively in the workplace. This study explores the
      collective spirituality of an interdisciplinary palliative care team, by studying
      how individuals felt about their own spirituality, whether there was a shared
      sense of a team spirituality, how spirituality related to the care the team
      provided to patients and whether they felt that they provided spiritual care.
      METHODS: A qualitative autoethnographic approach was used. The study was
      conducted in a 10-bed Tertiary Palliative Care Unit (TPCU) in a large acute-care
      referral hospital and cancer center. Interdisciplinary team members of the TPCU
      were invited to participate in one-to-one interviews and/or focus groups. Five
      interviews and three focus groups were conducted with a total of 20 participants.
      RESULTS: Initially participants struggled to define spirituality. Concepts of
      spirituality relating to integrity, wholeness, meaning, and personal journeying
      emerged. For many, spirituality is inherently relational. Others acknowledged
      transcendence as an element of spirituality. Spirituality was described as being
      wrapped in caring and often manifests in small daily acts of kindness and of
      love, embedded within routine acts of caring. Palliative care served as a
      catalyst for team members' own spiritual journeys. For some participants,
      palliative care represented a spiritual calling. A collective spirituality
      stemming from common goals, values, and belonging surfaced. SIGNIFICANCE OF
      RESULTS: This was the first known study that focused specifically on the
      exploration of a collective spirituality. The culture of palliative care seems to
      foster spiritual reflection among health care professionals both as individuals
      and as a whole. While spirituality was difficult to describe, it was a shared
      experience often tangibly present in the provision of care on all levels.

PMID- 16889321
TI  - The impact of supervised exercise intervention on short-term postprogram leisure
      time physical activity level in cancer patients undergoing chemotherapy: 1- and 3
      month follow-up on the body & cancer project.
AB  - BACKGROUND: Exercise is becoming an important component of cancer rehabilitation
      programs. A consistent finding across studies is that patients experience
      improved physical fitness and reduced fatigue. However, sustained physical
      activity is essential if the benefits are to be preserved over the course of
      cancer survivorship. OBJECTIVE: This study examined self-reported short-term
      exercise adherence following a 6-week, supervised exercise program (muscle
      strength, cardiovascular fitness, relaxation, body awareness, and massage) in a
      heterogeneous group of 61 cancer patients (mean age 42.9 years, 82% oncological
      and 18% haematological) from the Body & Cancer Project. METHODS: Semistructured
      interviews were used to quantitatively assess leisure time physical activity
      level 1 and 3 months after completion of the program. The study furthermore
      included 3-month follow-up assessment of psychological distress (Hospital Anxiety
      and Depression Scale-HADS). Patient statements were selected that best
      illustrated trends found in the statistical material. RESULTS: There was a
      significant postprogram reduction in physical activity from 6 to 10 weeks and
      from 6 to 18 weeks. However, the patients (half of whom were still undergoing
      treatment at the time of follow-up) reported a higher physical activity level
      postprogram compared to their baseline levels. The analyses showed a positive
      association between the 3-month postprogram physical activity level and pre
      illness physical activity level, treatment, and postprogram changes in
      depression. SIGNIFICANCE OF RESEARCH: Given the significant decrease in
      postprogram PA level, especially in subjects still undergoing cancer treatment,
      the study suggests that continuous supervised programs may be required in order
      to encourage and support exercise adherence in this population. However,
      randomized clinical controlled trials and more follow-up studies are needed to
      establish the optimal program length and content for sustained exercise adherence
      in cancer patients.

PMID- 16889322
TI  - An interdisciplinary workshop to improve palliative care: advanced heart failure-
      clinical guidelines and healing words.
AB  - OBJECTIVE: Effective communication is recognized as an essential process to
      providing quality care, including palliative and end-of-life care. Discussion of
      prognosis and support needs of patients with heart failure is particularly
      challenging given the nature of the condition and care across several settings.
      The objective was to design, implement, and evaluate an interdisciplinary
      workshop aimed at improving attitudes and skills related to communication with
      patients and family, health team communication and documentation, and assessment
      of physical and emotional symptoms. METHODS: A pretest, delayed posttest
      evaluation design was used to evaluate two 4-h workshops offered to nurses,
      social workers, and other nonphysician clinicians. RESULTS: Although baseline
      reports of skills were high for the participants, significant improvement was
      noted for objectives emphasized in the workshop. SIGNIFICANCE OF RESULTS: This
      project demonstrated the feasibility of designing, marketing a brief workshop,
      and positively impacting communication and documentation skills.

PMID- 16889323
TI  - Psychological morbidity and quality of life in women with advanced breast cancer:
      a cross-sectional survey.
AB  - OBJECTIVE: Our purpose was to determine the frequency of psychiatric morbidity
      and to assess the quality of life of women with advanced breast cancer. METHODS:
      The 227 women in the sample were recruited in Melbourne, Australia, and were
      interviewed (prior to intervention) for a randomized controlled trial of
      supportive-expressive group therapy. The main outcome measures were DSM-IV
      psychiatric diagnoses plus quality of life data based on the EORTC QLQ-C30 (core)
      and QLQ-BR23 (breast module) instruments. RESULTS: Forty-two percent of the women
      (97/227) had a psychiatric disorder; 35.7% (81) of these had depression or
      anxiety or both. Specific diagnoses were minor depression in 58 women (25.6%),
      major depression in 16 (7%), anxiety disorder in 14 (6.2%), and phobic disorder
      in 9 (4%). Seventeen (7.5%) women had more than one disorder. In terms of quality
      of life, one-third felt less attractive, one-quarter were dissatisfied with their
      body image, and, in most, sexual interest had waned. Menopausal symptoms such as
      hot flashes affected less than one-third, whereas symptoms of lymphedema were
      experienced by 26 (11.5%). SIGNIFICANCE: Women with advanced breast cancer have
      high rates of psychiatric and psychological disturbance. Quality of life is
      substantially affected. Clinicians need to be vigilant in monitoring
      psychological adjustment as part of a comprehensive biopsychosocial approach.

PMID- 16889324
TI  - Art therapy improves coping resources: a randomized, controlled study among women
      with breast cancer.
AB  - OBJECTIVE: Women with breast cancer suffer from considerable stress related to
      the diagnosis, surgery, and medical treatment. It is important to develop
      strategies to strengthen coping resources among these women. Research in art
      therapy has shown outcomes such as an increase in self-esteem and cohesion,
      significant improvement in global health, and a decrease in anxiety and
      depression. The aim of the present article was to describe the effects of an art
      therapy intervention program on coping resources in women with primary breast
      cancer. METHOD: In this article, we report some of the results from a study
      including 41 women, aged 37-69 years old, with nonmetastatic primary breast
      cancer, referred to the Department of Oncology at Umea University Hospital in
      Sweden for postoperative radiotherapy. The women represented various
      socioeconomic backgrounds. They were randomized to a study group (n = 20) with
      individual art therapy for 1 h/week during postoperative radiotherapy or to a
      control group (n = 21). The article focuses on changes in coping resources, as
      measured by the Coping Resources Inventory (CRI) before and 2 and 6 months after
      the start of radiotherapy. The study protocol was approved by the Umea University
      Ethical Committee at the Medical Faculty (archive number 99-386). RESULTS: There
      was an overall increase in coping resources among women with breast cancer after
      taking part in the art therapy intervention. Significant differences were seen
      between the study and control groups in the social domain on the second and third
      occasions. Significant differences were also observed in the total score on the
      second occasion. SIGNIFICANCE OF RESULTS: This study shows that individual art
      therapy provided by a trained art therapist in a clinical setting can give
      beneficial support to women with primary breast cancer undergoing radiotherapy,
      as it can improve their coping resources.

PMID- 16889325
TI  - Caregiver stress and burnout in an oncology unit.
AB  - PURPOSE: Caring for patients with cancer can be taxing for front-line health care
      providers. The growing intensity of treatment protocols, in conjunction with
      staff shortages, reduced hospital stays, and broader pressures on the health care
      system may exacerbate these challenges, leading to increased risk for burnout.
      This article reviews the research literature regarding the prevalence of burnout
      and psychosocial distress among oncology providers, examines multifactorial
      occupational and personal determinants of risk, and considers intervention
      strategies to enhance resilience. METHODS: Literature review of empirical peer
      reviewed studies focusing on prevalence and correlates of burnout among oncology
      physicians and nurses. RESULTS: Findings from a number of studies using validated
      measures and large samples suggest that prevalence rates for burnout and
      psychosocial distress are high among oncology staff, though not necessarily
      higher than in non-cancer-practice settings. A growing database has examined
      occupational (e.g., workload) and demographic (e.g., gender) factors that may
      contribute to risk, but there is less information about personal (e.g., coping)
      or organizational (e.g., staffing, physician-nurse relations) determinants or
      multilevel interactions among these factors. Oncologist burnout may adversely
      affect anticipated staff turnover. Other important endpoints (biological stress
      markers, health status, patient satisfaction, quality-of-care indices) have yet
      to be examined in the oncology setting. Intervention research is at a more
      rudimentary phase of development. CONCLUSIONS: Burnout and distress affect a
      significant proportion of oncology staff. There is a need for additional
      conceptually based, longitudinal, multivariate studies regarding burnout and its
      associated risk factors and consequences.

PMID- 16889326
TI  - The physician's role in the assessment and treatment of spiritual distress at the
      end of life.
AB  - OBJECTIVE: Patients at the end of their life typically endure physical,
      emotional, interpersonal, and spiritual challenges. Although physicians assume a
      clearly defined role in approaching the physical aspects of terminal illness, the
      responsibility for helping their patients' spiritual adaptation is also
      important. METHODS: This article (1) describes the terms and definitions that
      have clinical utility in assessing the spiritual needs of dying patients, (2)
      reviews the justifications that support physicians assuming an active role in
      addressing the spiritual needs of their patients, and (3) reviews clinical tools
      that provide physicians with a structured approach to the assessment and
      treatment of spiritual distress. RESULTS: This review suggests that physicians
      can and should be equipped to play a key role in relieving suffering at the end
      of life. SIGNIFICANCE OF RESULTS: Physicians can help their patients achieve a
      sense of completed purpose and peace.

PMID- 16889328
TI  - In the depths of human circumstance.

PMID- 16889327
TI  - Brief psychotic disorder mimicking the symptoms of cerebrovascular attack evoked
      by symptoms that symbolized death in a patient with terminal stage stomach
      cancer: case report and review of the literature.
AB  - OBJECTIVE: We report here a terminally ill patient with stomach cancer who
      developed a brief psychotic disorder mimicking cerebrovascular attack after a
      short episode of nasal bleeding. Close examination of the patient revealed that
      nasal bleeding was an event that symbolized deterioration of the general
      condition leading to death for the patient. METHODS: A 77-year-old male, who was
      diagnosed as having stomach cancer and was receiving palliative care, presented
      with tremor and insomnia just after a short episode of nasal bleeding and showed
      reduced response to stimuli mimicking cerebrovascular attack. Laboratory data
      were unremarkable. The next day, catatonic behavior developed. He had no history
      of psychiatric illness or drug or alcohol abuse. After receiving haloperidol,
      psychiatric symptoms disappeared and he returned to the previous level of
      functioning within 3 days. The patient explained that he had seen a patient whose
      general condition deteriorated after nasal bleeding and regarded nasal bleeding
      as a symptom of deteriorating general condition leading to death and thereafter
      became afraid of the nasal bleeding. RESULTS AND SIGNIFICANCE OF RESULTS:
      Although, nasal bleeding is common and usually not severe in medical settings,
      for the patient, it was an event that symbolized deterioration of the general
      condition leading to death. Brief psychotic disorder in cancer patients is rare
      in the literature, although patients receiving terminal care share various kinds
      of psychological burden. Medical staff in the palliative care unit should be
      aware of the psychological distress experienced by each patient and consider
      brief psychotic disorder as part of the differential diagnosis when patients show
      unexplained neurological-like and/or psychiatric symptoms.

PMID- 16889329
TI  - Inverted mesa-type quartz crystal resonators fabricated by deep-reactive ion
      etching.
AB  - In this letter, we present experimental data showing Q change versus thickness
      for a quartz-crystal resonator fabricated with deep-reactive ion etching.
      Measurements show that Q increases as etch depth increases, and further that Q
      can be optimized as a function of etch depth and diameter of the resonator.

PMID- 16889330
TI  - Mass sensitivity of thickness-shear modes in an isotropic elastic circular
      cylinder.
AB  - Theoretical prediction of the mass sensitivity of axial and tangential thickness
      shear modes in an isotropic elastic circular cylinder due to a thin surface mass
      layer is presented. Results suggest the possibility of new mass sensors with
      certain advantages.

PMID- 16889331
TI  - A domain evolution model for hysteresis in piezoceramic materials.
AB  - In this paper, we use a circular distribution to quantify certain domain
      properties and model the hysteresis behavior of piezoceramic materials. The model
      is constructed by bridging the characteristics of microscopic domain distribution
      into the macroscopic (or bulk) behavior. Contributions, other than those
      associated with the polarization of domains, to bulk quantities are also counted.
      A domain orientation distribution function is first selected and the
      corresponding distribution function parameters are chosen as the internal state
      variables. For the two-dimensional model, a von Mises-Fisher circular
      distribution is used. Instead of micromechanical analysis of domain motions that
      would involve large computation efforts, the delineation of domain evolution is
      simplified by considering the evolution of the domain orientation distribution,
      which is determined by the dynamic variations of the internal state variables. We
      also develop a procedure to identify the material constants introduced in the
      constitutive equations. The models are used to quantitatively characterize
      various hysteresis loops observed in piezoceramic materials.

PMID- 16889332
TI  - Continuous geodetic time-transfer analysis methods.
AB  - We address two issues that limit the quality of time and frequency transfer by
      carrier phase measurements from the Global Positioning System (GPS). The first
      issue is related to inconsistencies between code and phase observations. We
      describe and classify several types of events that can cause inconsistencies and
      observe that some of them are related to the internal clock of the GPS receiver.
      Strategies to detect and overcome time-code inconsistencies have been developed
      and implemented into the Bernese GPS Software package. For the moment, only
      inconsistencies larger than the 20 ns code measurement noise level can be
      detected automatically. The second issue is related to discontinuities at the day
      boundaries that stem from the processing of the data in daily batches. Two new
      methods are discussed: clock handover and ambiguity stacking. The two approaches
      are tested on data obtained from a network of stations, and the results are
      compared with an independent time-transfer method. Both methods improve the
      stability of the transfer for short averaging times, but there is no benefit for
      averaging times longer than 8 days. We show that continuous solutions are
      sufficiently robust against modeling and preprocessing errors to prevent the
      solution from accumulating a permanent bias.

PMID- 16889333
TI  - Impact of propagation through an aberrating medium on the linear effective
      apodization of a nonlinearly generated second harmonic field.
AB  - Techniques based on the nonlinearly generated second harmonic signal (tissue
      harmonic imaging) have rapidly supplanted linear (fundamental) imaging methods as
      the standard in two-dimensional echocardiography. Enhancements to the compactness
      of the nonlinearly generated second harmonic (2f) field component with respect to
      the fundamental (1f) field component are widely considered to be among the
      factors contributing to the observed image quality improvements. The objective of
      this study was to measure the impact of phase and amplitude aberrations resulting
      from propagation through an inhomogeneous tissue, on the beamwidths associated
      with: the fundamental (1f); the nonlinearly generated second harmonic (2f); and
      the linearly propagated, effective apodization signal at the same (21) frequency.
      Modifications to the transmit characteristics of a phased-array imaging system
      were validated with hydrophone measurements. Results demonstrate that the
      characteristics of the diffraction pattern associated with the linear-propagation
      effective apodization transmit case were found to be in good agreement with the
      detailed spatial characteristics of the nonlinearly generated second harmonic
      field. The effects of the abdominal wall tissue aberrators are apparent for all
      three of the beam profiles studied. Consistent with the improved image quality
      associated with harmonic imaging, the aberrated nonlinearly generated second
      harmonic beam was shown to remain more compact than the corresponding aberrated
      fundamental beam patterns in the presence of the interposed aberrator.

PMID- 16889334
TI  - Motion compensation for intravascular ultrasound palpography.
AB  - Rupture of vulnerable plaques in coronary arteries is the major cause of acute
      coronary syndromes. Most vulnerable plaques consist of a thin fibrous cap
      covering an atheromous core. These plaques can be identified using intravascular
      ultrasound (IVUS) palpography, which measures radial strain by cross-correlating
      RF signals at different intraluminal pressures. Multiple strain images (i.e.,
      partial palpograms) are averaged per heart cycle to produce a more robust
      compounded palpogram. However, catheter motion due to cardiac activity causes
      misalignment of the RF signals and thus of the partial palpograms, resulting in
      less valid strain estimates. To compensate for in-plane catheter rotation and
      translation, we devised four methods based on block matching. The global rotation
      block matching (GRBM) and contour mapping (CMAP) methods measure catheter
      rotation, and local block matching (LBM) and catheter rotation and translation
      (CRT) estimate displacements of local tissue regions. These methods were applied
      to nine in vivo pullback acquisitions, made with a 20 MHz phased-array
      transducer. We found that all these methods significantly increase the number of
      valid strain estimates in the partial and compounded palpograms (P < 0.008). The
      best method, LBM, attained an average increase of 17% and 15%, respectively.
      Implementation of this method should improve the information coming from IVUS
      palpography, leading to better vulnerable plaque detection.

PMID- 16889335
TI  - A 2-D anatomic breast ductal computer phantom for ultrasonic imaging.
AB  - Most breast cancers (85%) originate from the epithelium and develop first in the
      ductolobular structures. In screening procedures, the mammary epithelium should
      therefore be investigated first by the performing of an anatomically guided
      examination. For this purpose (mass screening, surgical guidance), we developed a
      two-dimensional anatomic phantom corresponding to an axial cross section of the
      ductolobular structures, which makes it possible to better understand the
      interactions between the breast composition and ultrasound. The various
      constitutive tissues were modeled as a random inhomogeneous continuum with
      density and sound speed fluctuations. Ultrasonic pulse propagation through the
      breast computer phantom was simulated using a finite element time domain method
      (the phantom can be used with other propagation codes). The simulated ductal
      echographic image is compared with the ductal tomographic (DT) reconstruction.
      The preliminary results obtained show that the DT method is more satisfactory in
      terms of both the contrast and the resolution.

PMID- 16889336
TI  - Directional velocity estimation using a spatio-temporal encoding technique based
      on frequency division for synthetic transmit aperture ultrasound.
AB  - This paper investigates the possibility of flow estimation using spatio-temporal
      encoding of the transmissions in synthetic transmit aperture imaging (STA). The
      spatial encoding is based on a frequency division approach. In STA, a major
      disadvantage is that only a single transmitter (denoting single transducer
      element or a virtual source) is used in every transmission. The transmitted
      acoustic energy will be low compared to a conventional focused transmission in
      which a large part of the aperture is used. By using several transmitters
      simultaneously, the total transmitted energy can be increased. However, to focus
      the data properly, the signals originating from the different transmitters must
      be separated. To do so, the pass band of the transducer is divided into a number
      of subbands with disjoint spectral support. At every transmission, each
      transmitter is assigned one of the subbands. In receive, the signals are
      separated using a simple filtering operation. To attain high axial resolution,
      broadband spectra must be synthesized for each of the transmitters. By
      multiplexing the different waveforms on different transmitters over a number of
      transmissions, this can be accomplished. To further increase the transmitted
      energy, the waveforms are designed as linear frequency modulated signals.
      Therefore, the full excitation amplitude can be used during most of the
      transmission. The method has been evaluated for blood velocity estimation for
      several different velocities and incident angles. The program Field II was used.
      A 128-element transducer with a center frequency of 7 MHz was simulated. The 64
      transmitting elements were used as the transmitting aperture and 128 elements
      were used as the receiving aperture. Four virtual sources were created in every
      transmission. By beamforming lines in the flow direction, directional data were
      extracted and correlated. Hereby, the velocity of the blood was estimated. The
      pulse repetition frequency was 16 kHz. Three different setups were investigated
      with flow angles of 45, 60, and 75 degrees with respect to the acoustic axis.
      Four different velocities were simulated for each angle at 0.10, 0.25, 0.50, and
      1.00 m/s. The mean relative bias with respect to the peak flow for the three
      angles was less than 2%, 2%, and 4%, respectively.

PMID- 16889338
TI  - Acoustic destruction of a microcapsule having a hard plastic shell.
AB  - Acoustic destruction of a microcapsule having a hard plastic shell is discussed.
      In an ultrasonic drug delivery system, microcapsules having thin elastic shells
      release drugs that are contained therein when the shell is destroyed. In this
      paper, two subjects related to capsule destruction are discussed: the driving
      pulse duration for capsule destruction and the frequency dependence of capsule
      destruction. Optical observation of microcapsule destruction is performed with a
      high-speed video camera. In the case of capsule destruction by a pulse wave, the
      internal gas of the microcapsule cannot be ejected completely, and a portion of
      the internal gas remains inside the broken shell. It is found that capsule
      destruction by pulse waves depends on both the amplitude of the driving pressure
      and the pulse duration. The frequency dependence of microcapsule destruction also
      is investigated. In the case of capsule destruction by a low-amplitude acoustic
      wave, the destruction rate under the resonance condition is higher than under
      nonresonance conditions. By controlling the driving frequency, selective capsule
      destruction can be achieved.

PMID- 16889339
TI  - Oscillatory interaction between bubbles and confining microvessels and its
      implications on clinical vascular injuries of shock-wave lithotripsy.
AB  - This paper presents a detailed study of the oscillation characteristics of a
      bubble confined inside a deformable microvessel, whose size is comparable with
      the bubble size. The vessel's compliance is characterized by a nonlinear relation
      between the intraluminal pressure and the expansion ratio of the vessel radius,
      which represents the variation of the vessel stiffness with the pressure of the
      filling liquid. In this analysis, an initially spherical bubble evolves into an
      ellipsoid, and the asymmetric oscillation appears immediately after the driving
      pressure is applied and magnifies with oscillation cycles. Compared with the
      symmetric oscillation in an unconstrained environment, the vessel constraint
      makes the bubble contract significantly more and subsequently expand in a more
      violent rebound, inducing substantially larger peaks of the intraluminal pressure
      exerted on the vessel wall. A larger initial bubble/vessel radius ratio leads to
      not only a larger peak but also a higher oscillation frequency of the
      intraluminal pressure, which are the two most dominating parameters in
      determining the vessel's failure under cyclic loading. The numerical results have
      further shown that an increase of the vessel wall stiffness strengthens the
      asymmetric effect, i.e., a larger peak of the intraluminal pressure with a higher
      oscillation frequency, and so does a larger pre-existing pressure in the liquid
      filling the vessel. These findings imply that the asymmetric effect is one of the
      primary mechanisms for clinical injuries of capillary and small blood vessels and
      for the higher risk of pediatric and hypertension patients in shock wave
      lithotripsy.

PMID- 16889337
TI  - Ultrasonic tracking of acoustic radiation force-induced displacements in
      homogeneous media.
AB  - The use of ultrasonic methods to track the tissue deformation generated by
      acoustic radiation force is subject to jitter and displacement underestimation
      errors, with displacement underestimation being primarily caused by lateral and
      elevation shearing within the point spread function (PSF) of the ultrasonic beam.
      Models have been developed using finite element methods and Field II, a linear
      acoustic field simulation package, to study the impact of focal configuration,
      tracking frequency, and material properties on the accuracy of ultrasonically
      tracking the tissue deformation generated by acoustic radiation force
      excitations. These models demonstrate that lateral and elevation shearing
      underneath the PSF of the tracking beam leads to displacement underestimation in
      the focal zone. Displacement underestimation can be reduced by using tracking
      beams that are narrower than the spatial extent of the displacement fields.
      Displacement underestimation and jitter decrease with time after excitation as
      shear wave propagation away from the region of excitation reduces shearing in the
      lateral and elevation dimensions. The use of higher tracking frequencies in
      broadband transducers, along with 2D focusing in the elevation dimension, will
      reduce jitter and improve displacement tracking accuracy. Relative displacement
      underestimation remains constant as a function of applied force, whereas jitter
      increases with applied force. Underdeveloped speckle (SNR < 1.91) leads to
      greater levels of jitter and peak displacement underestimation. Axial shearing is
      minimal over the tracking kernel lengths used in acoustic radiation force impulse
      imaging and thus does not impact displacement tracking.

PMID- 16889340
TI  - Broadband ultrasound field mapping system using a wavelength tuned, optically
      scanned focused laser beam to address a Fabry Perot polymer film sensor.
AB  - An optical system for rapidly mapping broad-band ultrasound fields with high
      spatial resolution has been developed. The transduction mechanism is based upon
      the detection of acoustically induced changes in the optical thickness of a thin
      polymer film acting as a Fabry Perot sensing interferometer (FPI). By using a PC
      controlled galvanometer mirror to line-scan a focused laser beam over the surface
      of the FPI, and a wavelength-tuned phase bias control system to optimally set the
      FPI working point, a notional 1D ultrasound array was synthesized. This system
      enabled ultrasound fields to be mapped over an aperture of 40 mm, in 50-microm
      steps with an optically defined element size of 50 microm and an acquisition time
      of 50 ms per step. The sensor comprised a 38-microm polymer film FPI which was
      directly vacuum-deposited onto an impedance-matched polycarbonate backing stub.
      The -3 dB acoustic bandwidth of the sensor was 300 kHz to 28 MHz and the peak
      noise-equivalent-pressure was 10 kPa over a 20-MHz measurement bandwidth. To
      demonstrate the system, the outputs of various planar and focused pulsed
      ultrasound transducers with operating frequencies in the range 3.5 to 20 MHz were
      mapped. It is considered that this approach offers a practical and inexpensive
      alternative to piezoelectric-based arrays and scanning systems for rapid
      transducer field characterization and biomedical and industrial ultrasonic
      imaging applications.

PMID- 16889341
TI  - Shear mode coupling and tilted grain growth of A1N thin films in BAW resonators.
AB  - Polycrystalline A1N thin films were deposited by RF reactive magnetron sputtering
      on Pt(111)/Ti electrode films. The substrates were tilted by an angle ranging
      from 40 degrees to 70 degrees with respect to the target normal. A low deposition
      temperature and a high sputter gas pressure were found ideal for tilted growth.
      The resulting grain tilt angle amounts to about half the substrate tilt angle.
      For coupling evaluation, 5 GHz solidly mounted resonator structures have been
      realized. The tilted grain A1N films exhibited a permittivity in the 9.5-10.5
      range and loss tangent of 0.3%. Two shear modes as well as the longitudinal mode
      could be clearly identified. The coupling coefficient k2(eff) of the fundamental
      thickness shear mode (TS0) was found to be about 0.5%, which is compatible with a
      c-axis tilt of about 6 degrees.

PMID- 16889342
TI  - A high-power traveling wave ultrasonic motor.
AB  - In the present work, a traveling wave ultrasonic motor (TWUSM) is proposed. It is
      composed of an annular-shaped stator and two cone-shaped rotors that are pressed
      in contact to the borders of the inner surface of the stator. A rotating
      traveling wave has been generated in the stator by using as vibration generators
      two bolted Langevin transducers (BLT) opportunely shifted in space and in time.
      The vibrational behavior of the stator as well as the traveling wave generation
      has been simulated with the finite-element method (FEM) software. A prototype of
      the motor has been manufactured and experimentally characterized. It exhibits a
      static torque of about 0.8 N x m and a maximum angular speed of about 300 rpm.
      Possible variations of the present design aimed to increase output torque or
      minimize encumbrance are described and discussed.

PMID- 16889343
TI  - Sensitivity analysis and optimization of a standing wave ultrasonic linear motor.
AB  - This paper presents the sensitivity analysis of an ultrasonic linear motor using
      design of experiments (DOE) and the finite element (FE) optimization of its
      deformation amplitude. A first ultrasonic linear motor prototype has been built
      at the laboratory. A deformation amplitude of about 6.6 microm can be obtained by
      applying a 100 V voltage. The goal is to obtain a bigger deformation amplitude by
      varying the motor parameters, in particular the vibratory piece dimensions. First
      of all, a parametrization of the motor structure is carried out. Then, with the
      aim of reducing the variation ranges of the input parameters--but also to avoid
      performing a large number of simulations--a preoptimization stage is necessary.
      Thus, sensitivity analysis is carried out using design of experiments, which is a
      good way to obtain the influence of the input parameters on the objective
      function. Factorial designs have been chosen to find out the effects of each
      input factor but also the effect of their interactions. This method then is
      compared with Doehlert design technique, which is generally used for optimization
      approaches. The results show that it is absolutely necessary to take into account
      the quadratic terms in the model because they represent an important effect. The
      use of design of experiments revealed to be an interesting way to analyze
      numerically the ultrasonic motor as a preoptimization stage and already allows
      one to improve the deformation amplitude but also to reduce the input parameter
      variation ranges. Different FE optimization methods are then applied, and results
      show that the deformation amplitude can be increased by a factor higher than 10
      compared to the initial design.

PMID- 16889344
TI  - Nonlinear processing of the output voltage of a piezoelectric transformer.
AB  - Reducing the size of power supplies raises the problem of new components that
      could be better candidates for integration. In this field, electromagnetic
      transformers may be replaced with significant benefit by piezoelectric
      transformers (PT). In a PT, the input electrical energy is transferred to the
      output by an acoustical means, using the direct and converse effects of
      piezoelectric materials. Its main advantages over an electromagnetic transformer
      are no magnetic noise generation, small size, high power density, and high
      efficiency. This paper deals with an innovative technique that produces a
      significant improvement of the power capability of piezoelectric transformers.
      This technique is based on a particular output voltage processing of the PT. Its
      effect is a vibration level reduction of the PT structure while keeping the
      output power practically constant. Vibration level is a critical parameter that
      determines the maximum power capability of a given PT. Thus, the new processing
      reduces significantly the losses of the PT. Both theoretical predictions and
      experimental results show that the increase of the power capability may reach
      200%.

PMID- 16889345
TI  - High-frequency piezopolymer transducers with a copper-clad polyimide backing
      layer.
AB  - The effect of a copper-clad polyimide (CCP) backing layer on piezopolymer
      transducer performance is evaluated. High-frequency, spherically curved
      polyvinylidene fluoride (PVDF) transducers with and without a CCP backing layer
      are electrically and acoustically tested. The results showed very similar
      operating characteristics. B-mode in vivo images of a mouse embryo also showed no
      qualitative differences, indicating that the CCP backing layer does not affect
      transducer performance.

PMID- 16889347
TI  - Nonlinear behavior of a piezoelectric power harvester near resonance.
AB  - We analyze the behavior of a model piezoelectric power harvester near resonance.
      Nonlinear effects of large deformations due to resonance are considered using a
      cubic theory of the displacement gradient. Results on the output current and
      power are presented, which exhibit multivaluedness and jump phenomena.

PMID- 16889346
TI  - Flexible acoustic fiber ultrasound motor modeling using impedance and
      transmission matrices.
AB  - The four-port matrix modeling is here applied to the power transfer mechanism
      through the different sections of the acoustic fiber motor, in order to evaluate
      the performances of the design. Analytical results are compared with experimental
      measurements on a motor prototype (fiber length 115 mm and diameter 0.8 mm,
      maximum torque 1.4 mNm, maximum speed 3200 rpm), showing a good agreement.

PMID- 16889348
TI  - [General approach to evaluation, comparison and norm-setting of health risks
      associated with various environmental factors].
AB  - The authors analyze modern approaches to health risk evaluation and establishing
      safety standards concerning ionizing radiation, chemicals, and other health
      hazard sources. Some recommendations on general approaches are given. A special
      individual risk index is offered to make decisions concerning human safety:
      establishing safety standards and other levels of protection, comparing different
      health hazard sources, etc. General approach to establishing public and
      occupational safety standards in terms of this index has been developed.

PMID- 16889349
TI  - [Important problems of high quality drinking water supply, and the ways of their
      solution].
AB  - The article covers the results of experimental and natural studies concerning
      important directions in the field of drinking water supply, including such
      aspects as: research into and classification of the barrier role of conventional
      and prospective technologies of water preparation in terms of chemical and
      biological pollution; revision of the standards of drinking water quality control
      in accordance with international documents; the main aspects of revision of the
      general conception of high quality water supply, within which hygienic
      requirements concerning the quality of prepackaged waters and the ranking of
      different techniques of water preparation used in water purification units, have
      been developed for the first time. The authors present the results of
      experimental studies on the patterns of disinfection, purification, and
      conditioning of drinking water quality using energetic- and-information
      technologies of water preparation.

PMID- 16889350
TI  - [Comparative evaluation of health hazards associated with industrial chemicals
      and their derivates forming during water chlorination].
AB  - Many industrial chemicals found in waste waters are able to form organochlorine
      by-products during water disinfection. The transformation of seven model
      compounds, cyclohexene, n-butanol, diphenylmethane, acetophenone, aniline, 1
      methylnaphthalene, and phenylxylylethane during a reaction with active chlorine
      was studied. Aqueous chlorine and sodium hypochlorite were used as chlorinating
      agents. The products of the reaction were analyzed by means of chromatomass
      spectrometry. A schematic model of diphenylmethane transformation was proposed.
      Comparative evaluation of hazards associated with the model chemicals and their
      derivates confirmed that chlorination products can be more toxic and dangerous
      than the initial compounds, and may possess mutagenic and cancerigenic
      properties.

PMID- 16889352
TI  - [Electrochemical purification of natural waters from humic compounds].
AB  - The article presents a comparative analysis of chemical substances which are
      formed in natural waters with different concentrations of humic and fulvic acids
      under the influence of ozone and chlorine, as a result of electrochemical
      processing. The authors present thermodynamic evaluation of the probability of
      the formation of transformation products under the influence of oxidizing
      reagents and during anode oxidation, and demonstrate the effectiveness of
      electrochemical purification of natural waters from humic compounds by cathode
      activated carbon. The scheme of a device to perform this process has been
      developed.

PMID- 16889351
TI  - [Improvement of sanitary-virologic monitoring of different waters].
AB  - The article is dedicated to present-day problems of sanitary-virologic monitoring
      of water with different degree of pollution. The authors assess some indirect
      indicators of viral contamination of water and present perfected methods of water
      monitoring such as PCR, OT-PCR, and OT-PCR integrated with tissue culture for
      detecting viral RNA and DNA.

PMID- 16889353
TI  - [Methodology of harmonizing hygienic standards for water substances, and its
      application to improving sanitary water legislation].
AB  - The article deals with methodology of harmonizing hygienic standards in order to
      correct and improve Russian sanitary water legislation. This methodology allows
      drawing on the world experience in the field of water hygiene, which is
      profitable in terms of cost-effectiveness and can contribute greatly to the
      national legislation.

PMID- 16889354
TI  - [A complex approach to evaluation of human genome instability].
AB  - In this study, evaluation of genome instability in individuals exposed to
      chemical compounds included detection of the genetic polymorphism of some
      xenobiotic metabolic enzymes (CYP1A1, CYP1E1, PON1, GSTM1, GSTT1), as well as
      measurement of oxidative state chemiluminescent variables and the level of
      cytogenetic damage. According to the study, the level of chromosomal aberrations
      in peripheral blood lymphocytes shows a strong correlation with PON54 left allele
      and GSTM1 null genotype, and can be described by the polynomial function of blood
      plasma luminol-dependent chemiluminescence. The frequencies of micronuclei in
      buccal epithelium displayed a weak association with GSTT1 null genotype.

PMID- 16889355
TI  - [Proliferative activity parameters and their correlation with genetic damage of
      blood lymphocytes during cultivation under the conditions of cytokinetic block].
AB  - The subjects of the study were 15 volunteers aged 22 to 25 years, who underwent
      25 air ionization sessions. The effects of genome instability were evaluated, and
      correlations between indicators of genome damage (lesions of micronuclei and
      nucleoplasmatic bridges) and parameters of proliferative and replicative activity
      (mitotic index, proliferative pool, the fraction of rapidly dividing cells, and
      replication index) of blood lymphocytes in the culture were studied. In order to
      establish the associations between the parameters, the parallel cultures were
      exposed to 0.07 mM of the standard mutagen MNNG during 5 hours. The study showed
      that the course of air ionization did not induce the micronuclei and
      nucleoplasmatic bridges in binuclear cells, but increased proliferative cell
      activity. This effect was accompanied by an increase in the fraction of rapidly
      dividing cells among all the dividing cells, and an increase in the dispersion of
      all proliferation parameters. MNNG induced a constant level of micronuclei in
      binuclear cells during the whole course, but not before the beginning of air
      ionization. The changes in the parameter "the fraction of dividing cells"
      (proliferative pool) were the most prominent manifestation of the suppression of
      proliferation by MNNG. MNNG loading inhibited the formation of binuclear cells
      most of all. The results demonstrate a non-random character of the correlation
      between the level of micronuclei in binuclear cells and proliferative activity
      parameters during cell cultivation under the conditions of cytokinetic block.

PMID- 16889356
TI  - [Application of quantum-chemical methods to prediction of the carcinogenicity of
      chemical substances].
AB  - A version of logical-combinatorial JSM type intelligent system was used to
      predict the presence and the degree of a carcinogenic effect. This version was
      based on combined description of chemical substances including both structural
      and numeric parameters. The new version allows for the fact that the toxicity and
      danger caused by chemical substances often depend on their biological activation
      in the organism. The authors substantiate classifying chemicals according to
      their carcinogenic activity, and illustrate the use of the system to predict the
      carcinogenicity of polycyclic aromatic hydrocarbons using a model of
      bioactivation via the formation of diolepoxides, and the carcinogenicity of
      halogenated alkanes using a model of bioactivation via oxidative dehalogenation.
      The paper defined the boundary level of an energetic parameter, the exceeding of
      which correlated with the inhibition of halogenated alkanes's metabolism and the
      absence of carcinogenic activity.

PMID- 16889357
TI  - What do we know and when do we know it? Hypnosis research, Cochrane reviews, and
      evidence-based medicine.

PMID- 16889358
TI  - An early nineteenth century absorption-based theory of mesmerism.
AB  - In 1844, an obscure and little-remembered American theorist, A. Yorke (no further
      identification is available), published a theory of mesmerism based on
      absorption, i.e., mental concentration. Unlike Mesmer's conceptualization of
      animal magnetism as a biological fluid, however, Yorke's theory emphasized the
      psychological importance of the mutual interaction between mesmerist and subject.
      This paper discusses the latter's theory of absorption as an important
      development in neo-mesmerism, the circumstances that led him to his conclusions,
      and his role in advancing our knowledge of the historical origins of modern
      hypnosis.

PMID- 16889359
TI  - Hypnosis in film and television.
AB  - When a hypnotist appears on screen, expect evil. If his induction features
      'magnetic' hand passes, he's probably about to compel someone to commit a crime.
      Ifhe hypnotizes with an intense stare, his intent is likelier seduction-in fact
      many screen inductions are identical to the eye contact ethologists have labeled
      "the copulatory gaze." This paper explores to role of hypnosis in more than 230
      films in which it has been depicted and categorizes the--mostly negative-
      stereotypes about it. A handful of exceptions in which hypnosis is positive
      and/or realistic are examined. The discussion compares this to the role of
      psychotherapy and dreams in cinema. It discusses why hypnosis is so maligned and
      whether there is anything practitioners can do to alter the stereotype.

PMID- 16889360
TI  - Tele-hypnosis in the treatment of adolescent school refusal.
AB  - Few studies have presented the use of hypnosis in the treatment of school
      refusal. These studies haven't approached the problem of self-hypnosis during the
      stressful morning hours. This paper introduces a therapeutic approach, which
      utilizes known hypnotic techniques, but rehearses them via the telephone, while
      the patient is at his/her house or on the way to school and the therapist is at
      the office. Twelve school-refusal adolescents were treated with different
      hypnotherapy techniques. Equipped with cellular phones and with the therapist's
      availability, these adolescents could benefit from hypnosis as an alternative
      coping strategy when the anxiety occurred. Results showed that 8 of the
      participants maintained full-time attendance, 3 showed partial improvement and 1
      failed to improve his attendance. This study illustrates the benefits of self
      hypnosis in the treatment of school refusal, while also enabling the patient to
      maintain the connection with the therapist so that the anxiety may be confronted
      when it arises.

PMID- 16889361
TI  - Mind styles and the hypnotic induction profile: measure and match to enhance
      medical treatment.
AB  - Modern medical technology and economic impositions tend to dehumanize the medical
      patient. This paper describes a targeted use of the hypnotic modality for
      relationship building, symptom management, and restoring a sense of self to the
      patient. To humanize medical care one patient at a time, examples are given for
      the use of the Hypnotic Induction Profile, the Eye Roll sign and AOD (Apollonian
      Odyssean-Dionysian) Mind-Style Questionnaire as a basis for choosing bio-psycho
      social treatment strategies. This trio of assessments can be used together, in
      approximately 10 to 15 minutes, or separately, if treatment decisions need to be
      made in a few minutes or less. The hypothesis presented is that matching
      treatment strategies, with or without formal hypnosis, to hypnotic capacity and
      mind style can increase respectful care and efficacy of treatment outcome.
      Clinical examples will illustrate this approach to enhance recovery, morale, and
      maximize patients' ability to become active partners on their own behalf.

PMID- 16889362
TI  - The effect of hypnotherapeutic ego strengthening with female spouses of South
      African coronary artery bypass surgery patients.
AB  - In addition to exacerbating morbidity in male coronary artery bypass surgery
      (CABS) patients, their plight can also impose considerable strain on their female
      spouses' mood states, resulting in compromised quality of life. The current study
      was aimed at determining the impact of pre postoperative hypnotherapeutic ego
      strengthening (HES) on anxiety and depression in female spouses. It was conducted
      simultaneously with a recently published study of their CABS husbands' response
      to HES. Spouses whose husbands had been randomly assigned to an experimental
      group, were designated the experimental spouse group (n = 25) and spouses whose
      husbands constituted the control group, likewise comprised the control spouse
      group (n = 25). Assessment occurred preoperatively, on the day of discharge and
      at six week follow-up. Spouses in the experimental group (n = 25) were introduced
      to hypnotherapeutic ego strengthening (HES), pre and postoperatively. In the
      postoperative assessment experimental female spouses showed significantly reduced
      morbidity levels, which were maintained at follow-up. In contrast, females in the
      control group (n = 25) showed no change. The results supported the value of brief
      hypnotherapy as a means of psychologically empowering spouses whose husbands'
      were undergoing CABS.

PMID- 16889363
TI  - Combinatorial Bioengineering-Protein Display and its Development. Proceedings of
      an international symposium, December 2005, Honolulu, Hawaii.

PMID- 16889364
TI  - Photoimmobilization for microarrays.
AB  - A photoimmobilization method has been developed for the preparation of microarray
      biochips. This photoimmobilization method makes it possible to easily covalently
      immobilize various types of organic molecules and cells on a chip. In addition,
      by using hydrophilic polymers as matrixes, it is possible to reduce nonspecific
      interactions with biological components. Various proteins, antibodies, and cells
      have been microarrayed using this technique, and interactions between these
      proteins, antibodies, and cells have been investigated. This type of microarray
      biochip will be important for academic applications such as genomics, proteomics,
      and cellomics, and clinical analyses.

PMID- 16889365
TI  - Enhancement of cellulase activity by clones selected from the combinatorial
      library of the cellulose-binding domain by cell surface engineering.
AB  - To improve the cellulolytic activity of a yeast strain displaying endoglucanase
      IotaIota (EG II) from Trichoderma reesei, a combinatorial library of the
      cellulose-binding domain (CBD) of EG II was constructed by using cell surface
      engineering. When EG II degrades celluloses, CBD binds to cellulose, and its
      catalytic domain cleaves the glycosidic bonds of cellulose. CBD had a flat face,
      composed of five amino acids for binding. It was supposed that the three
      hydrophobic amino acid residues of the five amino acid residues were essential
      for binding to cellulose. Therefore, by improving the two remaining amino acid
      residues, construction of mutants with a combinatorial library of the two amino
      acids in CBD was carried out and binding ability and hydrolysis activity were
      measured. In the first screening by halo assay using the Congo Red staining
      method, about 200 of the 2000 colonies formed clear halos, and then five colonies
      with the clearest halos were finally selected. In the second screening, the
      binding ability of the five mutants to phosphoric acid-swollen Avicel was
      measured. In addition, the measurement of hydrolysis activity toward
      carboxymethylcellulose (CMC) using the screened mutants was carried out. As a
      result, the mutated EG II exhibiting higher binding ability (1.5-fold) had higher
      hydrolysis activity (1.3-fold) compared to the parent EG II-displaying yeast
      cell, demonstrating that CBD has confirmatively some effect on the cellulase
      activity through its binding ability of the enzyme to cellulose.

PMID- 16889367
TI  - Construction of a cultivation system of a yeast single cell in a cell chip
      microchamber.
AB  - A novel single cell screening system was constructed using a yeast cell chip in
      combination with the yeast cell surface engineering [NanoBiotechnology 2005, 1,
      105-111]. Enzymes or functional proteins displayed on a yeast cell surface can be
      used as a protein cluster. To achieve high-throughput screening of protein
      libraries on the cell surface, a catalytic reaction by a single cell-surface
      engineered yeast cell was successfully carried out in the microchamber on the
      yeast cell chip. After screening, to replicate a target cell for use in measuring
      of activity, DNA sequencing, and preservation, a novel single cell cultivation
      system in the yeast cell chip was constructed. To avoid damage of the rapid dry
      up of medium in the microchamber array, the yeast cell chip was modified with a
      protection sheet, so that the modified chip was like a micro-culture tank
      constructed on the yeast cell chip microchamber. As a result, single yeast cell
      cultivation in the yeast cell chip microchamber was observed, and the modified
      yeast cell chip was evaluated to be good for a single cell selection. The
      improvement showed that the single cell screening system coupled with the single
      cell cultivation using the modified yeast cell chip may be superior to that by a
      cell sorter for the isolation of a target cell and its practical use.

PMID- 16889366
TI  - Surface display of organophosphorus hydrolase on Saccharomyces cerevisiae.
AB  - The gene encoding organophosphorus hydrolase (OPH) from Flavobacterium species
      was expressed on the cell surface of Saccharomyces cerevisiae MT8-1 using a
      glycosylphosphatidylinositol (GPI) anchor linked to the C-terminal region of OPH.
      Immunofluorescence microscopy confirmed the localization of OPH on the cell
      surface, and fluorescence intensity measurement of cells revealed that 1.4 x
      10(4) molecules of OPH per cell were displayed. Seventy percent of OPH whole-cell
      activity was detected on the cell surface by protease accessibility assay. The
      activity of OPH was highly dependent on cell growth conditions. The maximum
      activity was obtained when cells were grown in a synthetic dextrose medium
      lacking tryptophan (SD-W) buffered by 2-[4-(2-hydroxyethyl)-1
      piperazinyl]ethanesulfonic acid (HEPES, 200 mM, pH 7.0) at 20 degrees C, and
      cobalt chloride was added at 0.1 mM. S. cerevisiae MT8-1 displaying OPH which
      exhibited a higher activity than Escherichia coli displaying OPH using the ice
      nucleation protein (INP) anchor. The use of S. cerevisiae MT8-1, which has a
      "generally regarded as safe (GRAS)" status, as a host for the easy expression of
      the OPH gene provides a new biocatalyst useful for simultaneous detoxification
      and detection of organophosphorus pesticides.

PMID- 16889368
TI  - Application of the arming system for the expression of the 380R antigen from red
      sea bream iridovirus (RSIV) on the surface of yeast cells: a first step for the
      development of an oral vaccine.
AB  - The cell surface is a functional interface between the inside and the outside of
      the cell. Moreover, cells have systems for anchoring surface specific proteins
      and for confining surface proteins to particular domains on the cell surface. For
      use in bioindustrial processes applied to oral vaccination, we consider that cell
      surface display systems must be useful and that the yeast Saccharomyces
      cerevisiae, the most suitable microorganism for practical purposes, is available
      as a host for genetic engineering because it can be subjected to many genetic
      manipulations. In particular, the rigid structure of the cell makes the yeast
      suitable for several of the applications. In this study, we describe the
      expression of one of the target antigens, 380R, from the red sea bream iridovirus
      (RSIV), which is one of the most common viral diseases in the cultured marine
      fish Pagrus major in Japan, using the arming yeast system and aiming at its
      application for oral vaccination. We first performed the molecular cloning and
      expression of the 380R antigen from RSIV in Escherichia coli. The nucleotide
      sequence of the 380R antigen was composed of an open reading frame (ORF) of 1360
      bp encoding a protein of 453 residues. To prepare a specific antibody against the
      380R antigen, the recombinant protein was overexpressed and purified in E. coli.
      As a result of indirect immunofluorescence with the specific antibody, we could
      observe the expression of the 380R antigen on the surface of the yeast cells.
      Thus, we have successfully prepared the source of an oral vaccine using cell
      surface display technology in yeast.

PMID- 16889369
TI  - Quantitative and dynamic analyses of G protein-coupled receptor signaling in
      yeast using Fus1, enhanced green fluorescence protein (EGFP), and His3 fusion
      protein.
AB  - The mechanism of G protein-coupled receptor (GPCR) signaling in yeasts is similar
      to that in mammalian cells. Therefore, yeasts can be used in GPCR assays, and
      several ligand detection systems using a pheromone signaling pathway in yeasts
      have been developed by employing yeasts with disrupted chromosomal genes that
      code for proteins producing specific effects. In this study, the construction of
      yeast strains that can detect ligand binding mediated by interactions between the
      G protein and GPCR using either fluorescence or auxotrophic selectivity is
      demonstrated. The strain was constructed by integrating the fusion gene of
      pheromone-responsive protein (FUS1), enhanced green fluorescence protein (EGFP),
      and auxotrophic marker protein (HIS3) into the FUS1 locus. Moreover, the
      influence of gene disruptions on the yeast signal transduction cascade is closely
      investigated with respect to both quantitative and dynamic aspects to further
      develop a high-throughput screening system for the GPCR assay using yeasts. Yeast
      strains with a disrupted SST2 gene, which is a member of the RGS (regulator of G
      protein signaling) family, and a disrupted FAR1 gene, which mediates cell cycle
      arrest in response to a pheromone, were monitored by measuring their fluorescence
      and growth rate. This method will be applicable to other comprehensive GPCR
      ligand screening methods.

PMID- 16889370
TI  - Pooling for improved screening of combinatorial libraries for directed evolution.
AB  - Following diversity generation in combinatorial protein engineering, a
      significant amount of effort is expended in screening the library for improved
      variants. Pooling, or combining multiple cells into the same assay well when
      screening, is a means to increase throughput and screen a larger portion of the
      library with less time and effort. We have developed and validated a Monte Carlo
      simulation model of pooling and used it to screen a library of beta-galactosidase
      mutants randomized in the active site to increase their activity toward
      fucosides. Here, we show that our model can successfully predict the number of
      highly improved mutants obtained via pooling and that pooling does increase the
      number of good mutants obtained. In unpooled conditions, we found a total of
      three mutants with higher activity toward p-nitrophenyl-beta-D-fucoside than that
      of the wild-type beta-galactosidase, whereas when pooling 10 cells per well we
      found a total of approximately 10 improved mutants. In addition, the number of
      "supermutants", those with the highest activity increase, was also higher when
      pooling was used. Pooling is a useful tool for increasing the efficiency of
      screening combinatorial protein engineering libraries.

PMID- 16889371
TI  - Detection of protein tyrosine phosphorylation by open sandwich fluoroimmunoassay.
AB  - In the era of proteomics, high-throughput screening of posttranslational
      modification states of proteins, especially protein phosphorylation, is
      considered of utmost importance. However, current protein phosphorylation
      detection methods depend on either the combination of proteolysis and mass
      spectrometry, or time-consuming immunoassay that requires inevitable washing
      processes. As a way to rapidly assay protein phosphorylation events, here we
      propose the use of Open Sandwich immunoassay that detects antigen-dependent
      stabilization of antibody variable region (Fv). As a model system, the heavy and
      light chain variable regions (V(H)/V(L)) of anti-phosphotyrosine antibody PY20
      were used to evaluate its performance. When V(H)/V(L) interaction was first
      estimated by phage ELISA, wild-type Fv showed a modest phosphotyrosine (PY)
      dependent increase in signal. However, after screening of mutants at an interface
      residue, one with weak V(H)/V(L) interaction (HQ39R) showed markedly improved
      (>200%) antigen-dependent signals. Using this mutant, two fusion proteins in
      which each variable region fragment was tethered to a GFP color variant were made
      (V(H)-eYFP/V(L)-eCFP) to monitor PY-induced fluorescence resonance energy
      transfer (FRET) between them. The results showed significant PY- or tyrosine
      phosphorylated peptide-induced enhancement in FRET in homogeneous solutions,
      indicating applicability of the method for rapid screening of tyrosine
      phosphorylation in vitro or in situ and possibly in vivo.

PMID- 16889372
TI  - Selection and properties for the recognition of P19 embryonic carcinoma stem
      cells.
AB  - The P19 cell is a pluripotent stem cell of murine teratocarcinoma. When treated
      with retinoic acid, P19 cells can be differentiated along a neural cell lineage
      in culture. To isolate peptides that bind to the stem cell, we employed a phage
      display technology with undifferentiated P19 cells as the target. To reduce
      nonspecific binding of phages to the cell surface, the phage libraries were
      preadsorbed to the differentiated P19 cells before each selection on the
      undifferentiated P19 cells. After eight rounds of the selection, No. 28 phage
      displaying ALPSTSSQMPQL-peptide was isolated. Immunofluorescence analysis
      revealed that No. 28 phage selectively binds to the undifferentiated P19 cells
      but not to the differentiated P19 cells or SHSY cell line. The chemically
      synthesized peptide ALPSTSSQMPQL presented on the No. 28 phage efficiently
      inhibited the binding of No. 28 phage to the undifferentiated P19 cells. This
      result confirmed that No. 28 phage binding to the cell was mediated by the
      displayed peptide. The identified peptide may be targeted to a marker expressed
      on the stem cell and thus become a practical tool for the isolation of somatic
      stem cells.

PMID- 16889373
TI  - A novel strategy for generation of monoclonal antibodies from single B cells
      using rt-PCR technique and in vitro expression.
AB  - Monoclonal antibodies (Mabs) are important biomolecules in immunology and have
      widespread applications in prognosis, diagnosis, and therapeutics. Here, we
      describe a novel approach called single-cell RT-PCR-linked in vitro expression
      (SICREX), which enables the high-throughput generation and screening of Mabs.
      This approach entails the isolation of B cells from immunized mouse spleen or
      human peripheral blood using magnetic microbeads conjugated with a B-cell
      selective marker, anti-CD19. The light chain (Lc) and Fd portion of heavy-chain
      (Hc) genes of each cell are separately amplified by RT-PCR and then combined with
      the sequences of a T7 promoter, a ribosome binding site (rbs), and a T7
      terminator by an overlapping PCR technique. The paired full-length DNA fragments
      of Lc and Hc genes from single B cells are simultaneously expressed by an
      Escherichia coli in vitro transcription and translation system followed by an
      enzyme-linked immunosorbent assay to find positive fragments possessing the
      affinity for the antigen. From spleen cells of an immunized mouse with calcium
      binding protein 40, a Fab fragment with K(d) of 1.6 (+/- 0.3) x 10(-8) against
      the antigen was obtained. From human peripheral blood, Fab fragments against a
      blood group B-BSA were obtained in a similar manner. The SICREX approach is
      simple, rapid and versatile, allowing the high-throughput generation of naturally
      paired Lc and Hc with antigen-binding activity from various animal sources.

PMID- 16889374
TI  - Construction of a Pichia pastoris cell-surface display system using Flo1p anchor
      system.
AB  - A Pichia pastoris cell-surface display system was constructed using a Flo1p
      anchor system, which was developed in Saccharomyces cerevisiae. The lipase from
      Rhizopus oryzae with a pro sequence (ProROL) was used as the model protein and
      was genetically fused to the anchor consisting of amino acids 1-1099 of Flo1p (FS
      anchor). The resulting fusion protein FSProROL was expressed under the control of
      the alcohol oxidase 1 promoter (pAOX1). The fluorescence microscopy of
      immunolabeled P. pastoris cells revealed that ProROL was displayed on the cell
      surface, and Western blot analysis revealed that the fusion protein FSProROL was
      noncovalently attached to the cell wall and highly glycosylated. The lipase
      activity of P. pastoris cells was affected by the methanol concentration for the
      induction phase. Surprisingly, the activity of lipase displayed on the cells
      incubated at 60 degrees C was not only stable but also increased to about 6.5
      times the initial value after 4 h incubation.

PMID- 16889375
TI  - Development of novel yeast cell surface display system for homo-oligomeric
      protein by coexpression of native and anchored subunits.
AB  - Streptavidin derived from Streptomyces avidinii was displayed on the cell surface
      of the yeast Saccharomyces cerevisiae by cell-surface engineering using two types
      of plasmid for the expression of a native subunit and an anchored subunit fused
      with the C-terminus of 318 amino acids of Flo1p containing a
      glycosylphosphatidylinositol anchor attachment signal. The displayed streptavidin
      had the binding ability for biotinylated compounds. This was confirmed by
      fluorescence microscopy after the adsorption of yeast cells displaying
      streptavidin and biotinylated fluorescein isothiocyanate. On the other hand,
      streptavidin produced by cells harboring only the plasmid for the expression of
      the anchored subunit showed a very low binding activity for biotinylated
      compounds. Cells displaying streptavidin may constitute novel whole-cell affinity
      adsorbents widely used for immunoassay and biosensing. This coexpression method
      will ensure that proteins, such as homo- and hetero-oligomeric proteins, are
      displayed on the cell surface in an active form.

PMID- 16889376
TI  - Enhancement of activity of lipase-displaying yeast cells and their application to
      optical resolution of (R,S)-1-benzyloxy-3-chloro-2-propyl monosuccinate.
AB  - Rhizopus oryzae lipase (ROL) was displayed on the cell surface of Saccharomyces
      cerevisiae via the Flo1 N-terminal region (1100 amino acids), which corresponds
      to a flocculation functional domain. The activity of lipase-displaying yeast
      whole-cell biocatalysts was enhanced 7.3-fold by incubation of the yeast cells at
      20 degrees C in distilled water for 8 days after 8 day cultivation. The amount of
      lipase molecules present in cell wall and intracellular fractions was found to be
      increased 4.5- and 1.8-fold, respectively, by incubation, which proves that ROL
      molecules are expressed during incubation. The ROL-displaying yeast whole-cell
      biocatalyst with enhanced activity was successfully catalyzed by optical
      resolution of the pharmaceutical precursor (R,S)-1-benzyloxy-3-chloro-2-propyl
      monosuccinate. Moreover, it showed stable activity through at least eight
      reaction cycles. These results demonstrate that ROL-displaying yeast cells with
      enhanced activity by incubation in distilled water are very effective in
      industrial bioconversion processes.

PMID- 16889377
TI  - In vivo 15N-enrichment of metabolites in suspension cultured cells and its
      application to metabolomics.
AB  - The incorporation of stable isotopes in suspension cultured cells is very simple
      and useful as a preliminary experimental method in the experimental scene of
      plant metabolomics to elucidate the metabolic profiles of mutants and
      transformants. Stable isotope methods would afford a dynamic explanation of
      turnover speed that would concern the metabolic flux. Utilization of suspension
      cultured cells allows genes to be easily induced or suppressed, culture
      conditions to be controlled, and samples to be easily prepared. Stable isotope
      tracing allows an index of metabolic flux to be obtained. Here we present an
      experiment feeding (15)N-labeled inorganic salts to Arabidopsis (cell line T87)
      and Coptis cultured cells. Results of a comparison of (15)N labeling ratios of
      amino acids derived from T87 cells cultured under light with those cultured in
      the dark corresponded to transcriptional expressions revealed by microarray
      experiments published previously, demonstrating the validity of this procedure.
      Furthermore, (15)N labeling ratios of Coptis cultured cells revealed arginine and
      lysine metabolism inhibition, which should result in inhibition of polyamine
      biosynthesis and cell division. This very simple experiment allowed us to uncover
      metabolic dynamic features of the plant cell. Therefore this method is very
      useful for forming working hypotheses and experimental design.

PMID- 16889378
TI  - Energy and emission benefits of alternative transportation liquid fuels derived
      from switchgrass: a fuel life cycle assessment.
AB  - We conducted a mobility chains, or well-to-wheels (WTW), analysis to assess the
      energy and emission benefits of cellulosic biomass for the U.S. transportation
      sector in the years 2015-2030. We estimated the life-cycle energy consumption and
      emissions associated with biofuel production and use in light-duty vehicle (LDV)
      technologies by using the Greenhouse gases, Regulated Emissions, and Energy use
      in Transportation (GREET) model. Analysis of biofuel production was based on
      ASPEN Plus model simulation of an advanced fermentation process to produce fuel
      ethanol/protein, a thermochemical process to produce Fischer-Tropsch diesel (FTD)
      and dimethyl ether (DME), and a combined heat and power plant to co-produce steam
      and electricity. Our study revealed that cellulosic biofuels as E85 (mixture of
      85% ethanol and 15% gasoline by volume), FTD, and DME offer substantial savings
      in petroleum (66-93%) and fossil energy (65-88%) consumption on a per-mile basis.
      Decreased fossil fuel use translates to 82-87% reductions in greenhouse gas
      emissions across all unblended cellulosic biofuels. In urban areas, our study
      shows net reductions for almost all criteria pollutants, with the exception of
      carbon monoxide (unchanged), for each of the biofuel production option examined.
      Conventional and hybrid electric vehicles, when fueled with E85, could reduce
      total sulfur oxide (SO(x)) emissions to 39-43% of those generated by vehicles
      fueled with gasoline. By using bio-FTD and bio-DME in place of diesel, SO(x)
      emissions are reduced to 46-58% of those generated by diesel-fueled vehicles. Six
      different fuel production options were compared. This study strongly suggests
      that integrated heat and power co-generation by means of gas turbine combined
      cycle is a crucial factor in the energy savings and emission reductions.

PMID- 16889379
TI  - Numerical simulation of oxygen delivery to muscle tissue in the presence of
      hemoglobin-based oxygen carriers.
AB  - This work represents a culmination of research on oxygen transport to muscle
      tissue, which takes into account oxygen transport due to convection, diffusion,
      and the kinetics of simultaneous reactions between oxygen and hemoglobin and
      myoglobin. The effect of adding hemoglobin-based oxygen carriers (HBOCs) to the
      plasma layer of blood in a single capillary surrounded by muscle tissue based on
      the geometry of the Krogh tissue cylinder is examined for a range of HBOC oxygen
      affinity, HBOC concentration, capillary inlet oxygen tension (pO(2)), and
      hematocrit. The full capillary length of the hamster retractor muscle was modeled
      under resting (V(max) = 1.57 x 10(-4) mLO(2) mL(-1) s(-1), cell velocity (v(c)) =
      0.015 cm/s) and working (V(max) = 1.57 x 10(-3) mLO(2) mL(-1) s(-1), v(c) = 0.075
      cm/s) conditions. Two spacings between the red blood cell (RBC) and the capillary
      wall were examined, corresponding to a capillary with and without an endothelial
      surface layer. Simulations led to the following conclusions, which lend
      physiological insight into oxygen transport to muscle tissue in the presence of
      HBOCs: (1) The reaction kinetics between oxygen and myoglobin in the tissue
      region, oxygen and HBOCs in the plasma, and oxygen and RBCs in the capillary
      lumen should not be neglected. (2) Simulation results yielded new insight into
      possible mechanisms of oxygen transport in the presence of HBOCs. (3) HBOCs may
      act as a source or sink for oxygen in the capillary and may compete with RBCs for
      oxygen. (4) HBOCs return oxygen delivery to muscle tissue to normal for varying
      degrees of hypoxia (inlet capillary pO(2) < 30 mmHg) and anemia (hematocrit <
      46%) for the hamster model.

PMID- 16889380
TI  - Characterization of three genes encoding the subunits of light-independent
      protochlorophyllide reductase in Chlorella protothecoides CS-41.
AB  - Light is necessary for hydrogenation of the D ring of protochlorophyllide leading
      to chlorophyllide formation in higher plants (light-dependent pathway), but it is
      not essential in phototrophic bacteria (dark pathway). Both pathways, however,
      occur in some algae, mosses, ferns, and gymnosperms, and each chloroplast genome
      of these organisms contains three genes, chlL, chlN, and chlB, encoding the three
      subunits of light-independent protochlorophyllide reductase (LIPOR) required for
      protochlorophyllide reduction in the dark. In this study, the three LIPOR genes
      chlL, chlN, and chlB were cloned from the chloroplast of Chlorella protothecoides
      CS-41 (CSIRO), which grew heterotrophically with considerable chlorophyll yield.
      Phylogenetic analysis of ChlL/BchL showed that C. protothecoides CS-41 and
      Chlorella vulgaris C-27 were closely related. Alignment of their amino acid
      sequences demonstrated that the conserved domains, including the ATP-binding
      motif and the Fe-S binding motif in the three subunits, were similar to those in
      nitrogenases. The three-dimensional structural model of ChlL revealed a
      hypothetical Fe-S center for redox control. Results from RT-PCR amplification
      indicated that the chlL gene in C. protothecoides contained a 951-bp intron, and
      the splicing catalytic core structure was similar to that of the light-regulated
      intron in the psbA gene of Chlamydomonas. The three genes were expressed in E.
      coli BL21. The sizes of ChlL, ChlN, and ChlB were estimated to be 38, 49, and 58
      kDa, respectively, based on the SDS-PAGE analysis.

PMID- 16889381
TI  - MFA for overdetermined systems reviewed and compared with rna expression data to
      elucidate the difference in shikimate yield between carbon- and phosphate-limited
      continuous cultures of E. coli W3110.shik1.
AB  - The present contribution focuses on the mathematical techniques used to solve
      steady state metabolic models for the case of an overdetermined system. Even when
      parts of the system are underdetermined it is possible to solve the model
      partially and obtain statistically meaningful results. This is illustrated with
      data gathered from a set of E. coli W3110.shik1 phosphate- or carbon-limited
      continuous cultures. It is shown that the low yield in shikimate for C-limited
      cultures is not due to a lower flux going to the shikimate pathway but is caused
      by a high secretion of byproducts. Carbon-limited cultures could be better for
      shikimate production than carbon-abundant cultures provided the byproduct
      secretion is reduced. Finally, flux calculations are compared with RNA expression
      data.

PMID- 16889383
TI  - Expression of single-chain Fv gene specific for gamma-seminoprotein by RTS and
      its biological activity identification.
AB  - Fabricating a single-chain variable fragment specific for human seminoprotein is
      very important in antibody-directed enzyme prodrug therapy and NMR imaging for
      prostate cancer. Here a single-chain Fv specific for gamma-seminoprotein was
      expressed by RTS. Its activity and the efficiency of entry into prostate cancer
      cells are investigated by immunoprecipitation and Western blotting and
      immunofluorescent staining, as well as entry of conjugated magnetic beads into
      cells. Results showed that ScFv peptides specific for gamma-seminoprotein were
      successfully prepared, which can bind with the prostate cells specifically and
      can bring magnetic beads into prostate cancer cells within 15 min, the amount of
      magnetic beads inside prostate cancer cells increased as the culture time
      prolonged. ScFv-conjugated magnetic beads did not enter into control cells. In
      conclusion, the ScFv peptide against human gamma-seminoprotein with biological
      activity was successfully fabricated, which can take magnetic beads to prostate
      cancer cells specifically and not to the control cells. This ScFv peptide against
      human gamma-seminoprotein should be useful in improving the detection and therapy
      of prostate cancer at early stages and NMR imaging.

PMID- 16889382
TI  - Monitoring and modeling of the reaction dynamics in the valine/leucine synthesis
      pathway in Corynebacterium glutamicum.
AB  - The intracellular concentrations of the valine and leucine pathway intermediates
      in a Corynebacterium glutamicum strain were measured during a transient state.
      The data were obtained by performing a glucose stimulus-response experiment with
      the use of a rapid sampling device and advanced mass spectrometry. The glucose
      stimulus resulted in a 3-fold increase in the intracellular pyruvate
      concentration within less than a second, demonstrating the very fast interactions
      in metabolic networks. The samples were taken at subsecond intervals for a time
      period of 25 s. The time courses of the metabolite concentrations formed the
      experimental basis of a mathematical model simulating the fluxes and
      concentrations in the valine/leucine pathway. The implementation of a model
      selection criterion based on the second law of thermodynamics is demonstrated to
      be essential for the identification of realistic and unique models. Large
      differences between the enzyme properties determined in vitro and those
      determined in vivo by the model were observed with the in vivo maximal rates
      being almost an order of magnitude larger than the in vitro maximal rates. The
      transamination of ketoisovalerate (KIV) to valine is carried out mainly by the
      transaminase B enzyme, with the transaminase C enzyme playing a minor role. The
      availability of the cofactors NADP and NADPH only has modest influence on the
      flux through the valine pathway, while the influence of NAD and NADH on the flux
      through the leucine pathway is negligible.

PMID- 16889385
TI  - Expression of an Aspergillus niger glucose oxidase in saccharomyces cerevisiae
      and its use to optimize fructo-oligosaccharides synthesis.
AB  - Fructo-oligosaccharides (FOS) represent the most abundantly supplied and utilized
      group of nondigestible oligosaccharides as food ingredients. These prebiotics can
      be produced from sucrose using the transglycosylating activity of beta
      fructofuranosidases (EC 3.2.1.26) at high concentrations of the starting
      material. The main problem during FOS synthesis is that the activity of the
      enzyme is inhibited by the glucose generated during the reaction, and therefore
      the maximum FOS content in commercial products reaches up to 60% on a dry
      substance basis. The glucose oxidase (gox) gene from Aspergillus niger BT18 was
      cloned and integrated, as part of an expression cassette, into the ribosomal DNA
      of a Saccharomyces cerevisiae host strain. One of the recombinant strains with a
      high copy number of the gox gene and showing a high GOX specific activity was
      used to produce the enzyme. Addition of the extracellular glucose oxidase to the
      FOS synthesis reaction helped to remove the glucose generated, avoiding the
      inhibition of the fungal beta-fructofuranosidase. As a result, a final syrup
      containing up to 90% of FOS was obtained.

PMID- 16889384
TI  - Enhanced secretion of heterologous proteins in Pichia pastoris following
      overexpression of Saccharomyces cerevisiae chaperone proteins.
AB  - In Pichia pastoris, secretory proteins are folded and assembled in the
      endoplasmic reticulum (ER). However, upon introduction of foreign proteins,
      heterologous proteins are often retained in the cytoplasm or in the ER as a
      result of suboptimal folding conditions, leading to protein aggregation. The
      Hsp70 and Hsp40 chaperone families in the cytoplasm or in ER importantly regulate
      the folding and secretion of heterologous proteins. However, it is not clear
      which single chaperone is most important or which combination optimally
      cooperates in this process. In the present study we evaluated the role of the
      chaperones Kar2p, Sec63, YDJ1p, Ssa1p, and PDI from Saccharomyces cerevisiae. We
      found that the introduction of Kar2p, Ssa1p, or PDI improves protein secretion 4
      7 times. In addition, we found that the combination chaperones of YDJ1p/PDI,
      YDJ1p/Sec63, and Kar2p/PDI synergistically increase secretion levels 8.7, 7.6,
      and 6.5 times, respectively. Therefore, additional integration of chaperone genes
      can improve the secretory expression of the heterologous protein. Western blot
      experiments revealed that the chaperones partly relieved the secretion bottleneck
      resulting from foreign protein introduction in P. pastoris. Therefore, the
      findings from the present study demonstrate the presence of a network of
      chaperones in vivo, which may act synergistically to increase recombinant protein
      yields.

PMID- 16889387
TI  - Surface functionalized electrospun biodegradable nanofibers for immobilization of
      bioactive molecules.
AB  - A blend mixture of biodegradable poly(epsilon-caprolactone) (PCL) and poly(d,l
      lactic-co-glycolic acid)-poly(ethylene glycol)-NH(2) (PLGA-b-PEG-NH(2)) block
      copolymer was electrospun to produce surface functionalized nanofibers. The
      resulting nanofibrous mesh with primary amine groups on the surface was applied
      for immobilization of biologically active molecules using lysozyme as a model
      enzyme. Lysozyme was immobilized via covalent conjugation by using a
      homobifunctional coupling agent. The nanofibrous mesh could immobilize a far
      greater amount of lysozyme on the surface with concomitantly increased activity,
      primarily due to its larger surface area, compared to that of the solvent casting
      film. It was also found that the enzyme immobilization process slightly altered
      thermal and pH-dependent catalytic activity profiles compared to those of native
      lysozyme. The results demonstrated the surface functionalized electrospun
      nanofibrous mesh could be used as a promising material for immobilizing a wide
      range of bioactive molecules.

PMID- 16889386
TI  - Chip-based polyketide biosynthesis and functionalization.
AB  - We demonstrate construction and novel compound synthesis from a synthetic
      metabolic pathway consisting of a type III polyketide synthase (PKS) known as
      1,3,6,8-tetrahydroxynaphthalene synthase (THNS) from Streptomyces coelicolor and
      soybean peroxidase (SBP) in a microfluidic platform. THNS immobilized to Ni-NTA
      agarose beads is prepacked into a microfluidic channel, while SBP is covalently
      attached to the walls of a second microfluidic channel precoated with a reactive
      poly(maleic anhydride) derivative. The result is a tandem, two-step biochip that
      enables the synthesis of novel polyketide derivatives. The first microchannel,
      consisting of THNS, results in the conversion of malonyl-CoA to flaviolin in
      yields up to 40% with a residence time of 6 min. This conversion is similar to
      that obtained in several-milliliter batch reactions after 2 h. Linking this
      microchannel to the SBP microchannel results in biflaviolin synthesis. During the
      course of this work, we discovered that the substrate specificity of THNS could
      be manipulated by simply changing the reaction pH. As a result, the starter acyl
      CoA specificity can be broadened to yield a series of truncated pyrone products.
      When combined with variations in the ratio of acyl-CoA and malonyl-CoA (extender
      substrate) feed rates, high yields of the pyrone products could be achieved,
      which is further structurally diversified from self- and cross-coupling in the
      SBP microchannel. The ability to rapidly evaluate the effects of reaction
      conditions and synthetic multienzyme pathways on a microfludic platform provides
      a new paradigm for performing metabolic pathway engineering, namely, the
      reconstruction of pathways for use in new compound discovery.

PMID- 16889388
TI  - Toward a stochastic formulation of microbial growth in relation to bioreactor
      performances: case study of an E. coli fed-batch process.
AB  - A stochastic microbial growth model has been elaborated in the case of the
      culture of E. coli in fed-batch and scale-down reactors. This model is based on
      the stochastic determination of the generation time of the microbial cells. The
      determination of generation time is determined by choosing the appropriate value
      on a log-normal distribution. The appropriateness of such distribution is
      discussed and growth curves are obtained that show good agreement compared with
      the experimental results. The mean and the standard deviation of the log-normal
      distribution can be considered to be constant during the batch phase of the
      culture, but they vary when the fed-batch mode is started. It has been shown that
      the parameters related to the log-normal distribution are submitted to an
      exponential evolution. The aim of this study is to explore the bioreactor
      hydrodynamic effect on microbial growth. Thus, in a second time, the stochastic
      growth model has been reinforced by data coming from a previous stochastic
      bioreactor mixing model (1). The connection of these hydrodynamic data with the
      actual stochastic growth model has allowed us to explain the scale-down effect
      associated with the glucose concentration fluctuations. It is important to point
      out that the scale-down effect is induced differently according to the feeding
      strategy involved in the fed-batch experiments.

PMID- 16889389
TI  - Characteristics of a mesoporous silicate immobilized trypsin bioreactor in
      organic media.
AB  - Mesoporous silicates (MPS) materials are attractive materials for immobilizing
      proteins/enzymes because of their well ordered structures, large surface areas
      (up to 1000 m(2) g(-1)), narrow pore size distributions, large pore diameters,
      and pore volumes. MPS with average pore diameters ranging from 28 to 300
      Angstroms were prepared using cationic and nonionic surfactants. The influence of
      water content, pH, storage, and thermal treatment on the activity of trypsin
      immobilized onto MPS was investigated. In a range of solvents, the amidolytic
      activity of immobilized trypsin was higher than that of the lyophilized
      preparation. Significant increases in k(cat)/K(M) occurred in propanol, ethanol,
      methanol, and formamide of 90, 62, 45 and 26, respectively. The observed
      increases were primarily a result of substantial increases in k(cat).

PMID- 16889390
TI  - A study of long-term effects on plasmid-containing Escherichia coli in carbon
      limited chemostat using 2D-fluorescence spectrofluorimetry.
AB  - Strain stability of plasmid-containing recombinant organisms is clearly important
      for industrial applications. Stability is normally assessed by methods such as
      selective colony forming units or by simply measuring the recombinant product.
      These methods are typically performed off-line, are time-consuming, and do not
      give detailed information on the changes in the metabolism. In the current work,
      long-term stability of a plasmid-containing strain of Escherichia coli
      (W3110.shik1) capable of shikimic acid overproduction was studied by means of a
      2D-fluorescence sensor (BioView) able to emit and detect light in ranges of 260
      560 nm and 300-600 nm, respectively. Long-term carbon-limited chemostat
      experiments were made under both selective (tetracycline-containing medium) and
      nonselective conditions. It is shown that the fluorescence spectra provide
      information about metabolic changes at an earlier stage, thereby giving a
      noninvasive method for monitoring of strain stability. Further, the fluorescence
      measurements showed that (i) the metabolic changes in the strain W3110.shik1 with
      time were qualitatively different in selective and nonselective environment, (ii)
      plasmid recombination resulted primarily in increased biomass yield, and (iii) a
      change in metabolism probably involving FAD/FMN and pyridoxal-5-P occurred in all
      experiments. It was concluded that the strain was not stable in any growth
      condition for more than about 25 growth generations and even less if plasmid
      recombination took place.

PMID- 16889391
TI  - Immobilization and stabilization of a cyclodextrin glycosyltransferase by
      covalent attachment on highly activated glyoxyl-agarose supports.
AB  - Covalent immobilization of cyclodextrin glycosyltransferase on glyoxyl-agarose
      beads promotes a very high stabilization of the enzyme against any distorting
      agent (temperature, pH, organic solvents). For example, the optimized immobilized
      preparation preserves 90% of initial activity when incubated for 22 h in 30%
      ethanol at pH 7 and 40 degrees C. Other immobilized preparations (obtained via
      other immobilization protocols) exhibit less than 10% of activity after
      incubation under similar conditions. Optimized glyoxyl-agarose immobilized
      preparation expressed a high percentage of catalytic activity (70%).
      Immobilization using any technique prevents enzyme inactivation by air bubbles
      during strong stirring of the enzyme. Stabilization of the enzyme immobilized on
      glyoxyl-agarose is higher when using the highest activation degree (75 micromol
      of glyoxyl per milliliter of support) as well as when performing long enzyme
      support incubation times (4 h) at room temperature. Multipoint covalent
      immobilization seems to be responsible for this very high stabilization
      associated to the immobilization process on highly activated glyoxyl-agarose. The
      stabilization of the enzyme against the inactivation by ethanol seems to be
      interesting to improve cyclodextrin production: ethanol strongly inhibits the
      enzymatic degradation of cyclodextrin while hardly affecting the cyclodextrin
      production rate of the immobilized-stabilized preparation.

PMID- 16889392
TI  - In silico prediction of medium effects on esterification equilibrium using the
      COSMO-RS method.
AB  - This paper presents a new approach for predicting solvent effects on
      esterification reactions of industrial importance in the field of biocatalysis.
      The COSMO-RS method has been used to calculate the activity coefficients of the
      chemical species involved in various reactions, carried out in different
      solvents. For comparison we also used the traditional UNIFAC method. Three lipase
      catalyzed esterifications were considered: (1) 1-dodecanoic acid with menthol in
      n-hexane, n-heptane, cyclohexane, 2,2,4-trimethylpentane, toluene, acetonitrile,
      and 2-methyl-2-butanol; (2) 1-dodecanoic acid and 1-dodecanol in n-hexane, n
      heptane, cyclohexane, 2,2,4-trimethylpentane, and toluene; and (3) glycerol and n
      octanoic acid in acetonitrile, benzene, and toluene and in the neat reaction
      mixture (without any solvent). Predicted activities were used to calculate the
      thermodynamic equilibrium ratio. This should be independent of medium, and the
      variation in COSMO-RS values is at most 9-fold (corresponding to a DeltaG degrees
      of about 5.5 kJ/mol, which would still be a very useful prediction) and often
      only 2-fold (corresponding to less than 2 kJ/mol or 0.5 kcal/mol, therefore
      comparable with experimental error). UNIFAC is weaker, especially when important
      roles are played by conformational freedom, intramolecular interactions, strong
      polar effects, and charge distribution of molecules in the mixture. The relative
      percent deviations from the mean of equilibrium constants in different solvents
      range between 17 and 49 for COSMO-RS versus 32 to 65 for UNIFAC. The COSMO-RS
      method opens up new perspectives for the development of theoretical models for
      solvent selection with general applicability.

PMID- 16889393
TI  - Ion-exchange purification of proteins using magnetic nanoclusters.
AB  - Polymer-coated magnetic nanoclusters were used for recovery and purification of
      proteins from both model systems and cell-free Pichia pastoris fermentation
      broth. The nanoclusters exhibited extremely high capacity for proteins, up to 900
      mg/mL adsorbent, and were recovered by high gradient magnetic separation (HGMS)
      at flow rates of up to 3,600 cm(3)/cm(2) h (flow rates up to 15,000 cm(3)/cm(2) h
      are possible). The nanoclusters were coated with a primary coating of
      poly(acrylic acid-co-styrenesulfonic acid-co-vinylsulfonic acid), which allowed
      both electrostatic and hydrophobic interactions with the protein to be used to
      enhance specificity for targeted products. With this dual mode separation, nearly
      pure protein could be recovered from complex mixtures, such as fermentation
      broth, in a few quick steps.

PMID- 16889394
TI  - Protein fouling of virus filtration membranes: effects of membrane orientation
      and operating conditions.
AB  - The capacity of virus filters used in the purification of therapeutic proteins is
      determined by the rate and extent of membrane fouling. Current virus filtration
      membranes have a complex multilayer structure that can be used with either the
      skin-side up or with the skin-side facing away from the feed, but there is
      currently no quantitative understanding of the effects of membrane orientation or
      operating conditions on the filtration performance. Experiments were performed
      using Millipore's Viresolve 180 membrane under both constant pressure and
      constant flux operation with sulfhydryl-modified BSA used as a model protein. The
      capacity with the skin-side up was greater during operation with constant flux
      and at low transmembrane pressures, with the flux decline or pressure rise due
      primarily to osmotic pressure effects. In contrast, data obtained with the skin
      side down showed a slower, steady increase in total resistance with the
      cumulative filtrate volume, with minimal contribution from osmotic pressure. The
      capacity with the skin-side down was significantly greater than that with the
      skin-side up, reflecting the different fouling mechanisms in the different
      membrane orientations. These results provide important insights for the design
      and operation of virus filtration membranes.

PMID- 16889395
TI  - Design and characterization of stimuli-responsive FLAG-tag analogues and the
      illumination-induced modulation of their interaction with antibody 4E11.
AB  - An azobenzene group containing beta-amino acid N-Fmoc-4-aminomethyl
      phenylazobenzoic acid was synthesized and with the exception of the C-terminal
      amino acid residue was substituted by solid-phase peptide synthesis into all
      positions of the FLAG sequence (DYKDDDDK), an octapeptide capable of specific
      interaction with the monoclonal antibody 4E11. The trans state of the beta-amino
      acid was thermodynamically more stable than the cis state. However, the molecule
      could be switched into the cis conformation by illumination at 340 nm. Peptides
      containing the artificial amino acid also became photoresponsive. In the absence
      of light, the spontaneous back-isomerization into the trans conformation of the
      photoresponsive was extremely slow (>8 h no significant increase in trans
      content). When illuminated with visible light (440 nm), the back-isomerization
      from the cis to the trans state was accelerated and occurred with a half-life of
      approximately 10 min. The cis form of the photopeptides was more hydrophilic than
      the trans form, as evidenced by differences in the retention time of the two
      isomeric forms in reversed-phase chromatography. Photopeptides that contained the
      intact sequences responsible for binding of the FLAG tag to the antibody, namely,
      the DYK motive at the N-terminus, showed binding to the antibody in both a dot
      blot immunoassay and in Biacore binding studies, albeit with lower affinity than
      the unmodified FLAG sequence. Peptides with a substitution in positions 4-6
      showed differences in binding strength between the trans and the cis form in the
      Biacore studies, no such difference could be observed for the peptide with a
      substitution in position 7.

PMID- 16889396
TI  - Optimization of isopropanol and ammonium sulfate precipitation steps in the
      purification of plasmid DNA.
AB  - Large-scale processes used to manufacture grams of plasmid DNA (pDNA) should be
      cGMP compliant, economically feasible, and environmentally friendly. Alcohol and
      salt precipitation techniques are frequently used in plasmid DNA (pDNA)
      downstream processing, as concentration and prepurification steps, respectively.
      This work describes a study of a standard 2-propanol (IsopOH; 0.7 v/v) and
      ammonium sulfate (AS; 2.5 M) precipitation. When inserted in a full process, this
      tandem precipitation scheme represents a high economic and environmental impact
      due to the large amounts of the two precipitant agents and their environmental
      relevance. Thus, major goals of the study were the minimization of precipitants
      and the selection of the best operating conditions for high pDNA recovery and
      purity. The pDNA concentration in the starting Escherichia coli alkaline lysate
      strongly affected the efficiency of IsopOH precipitation as a concentration step.
      The results showed that although an IsopOH concentration of at least 0.6 (v/v)
      was required to maximize recovery when using lysates with less than 80 microg
      pDNA/mL, concentrations as low as 0.4 v/v could be used with more concentrated
      lysates (170 microg pDNA/mL). Following resuspension of pDNA pellets generated by
      0.6 v/v IsopOH, precipitation at 4 degrees C with 2.4 M AS consistently resulted
      in recoveries higher than 80% and in removal of more than 90% of the impurities
      (essentially RNA). An experimental design further indicated that AS
      concentrations could be reduced down to 2.0 M, resulting in an acceptable purity
      (21-23%) without compromising recovery (84-86%). Plasmid recovery and purity
      after the sequential IsopOH/AS precipitation could be further improved by
      increasing the concentration factor (CF) upon IsopOH precipitation from 2 up to
      25. Under these conditions, IsopOH and AS concentrations of 0.60 v/v and 1.6 M
      resulted in high recovery (approximately 100%) and purity (32%). In conclusion,
      it is possible to reduce substantially the mass of precipitation agents used
      without affecting recovery, if a small concession is made regarding purity. This
      directly translates into an improvement of the process economics and in a
      reduction of the environmental impact of the process.

PMID- 16889397
TI  - Intensified process for the purification of an enzyme from inclusion bodies using
      integrated expanded bed adsorption and refolding.
AB  - This work describes the integration of expanded bed adsorption (EBA) and
      adsorptive protein refolding operations in an intensified process used to recover
      purified and biologically active proteins from inclusion bodies expressed in E.
      coli. Delta(5)-3-Ketosteroid isomerase with a C-terminal hexahistidine tag was
      expressed as inclusion bodies in the cytoplasm of E. coli. Chemical extraction
      was used to disrupt the host cells and simultaneously solubilize the inclusion
      bodies, after which EBA utilizing immobilized metal affinity interactions was
      used to purify the polyhistidine-tagged protein. Adsorptive refolding was then
      initiated in the column by changing the denaturant concentration in the feed
      stream from 8 to 0 M urea. Three strategies were tested for performing the
      refolding step in the EBA column: (i) the denaturant was removed using a step
      change in feed-buffer composition, (ii) the denaturant was gradually removed
      using a gradient change in feed-buffer composition, and (iii) the liquid flow
      direction through the column was reversed and adsorptive refolding performed in
      the packed bed. Buoyancy-induced mixing disrupted the operation of the expanded
      bed when adsorptive refolding was performed using either a step change or a rapid
      gradient change in feed-buffer composition. A shallow gradient reduction in
      denaturant concentration of the feed stream over 30 min maintained the stability
      of the expanded bed during adsorptive refolding. In a separate experiment,
      buoyancy-induced mixing was completely avoided by performing refolding in a
      settled bed, which achieved comparable yields to refolding in an expanded bed but
      required a slightly more complex process. A total of 10% of the available KSI
      (His(6)) was recovered as biologically active and purified protein using the
      described purification and refolding process, and the yield was further increased
      to 19% by performing a second iteration of the on-column refolding operation.
      This process should be applicable for other polyhistidine tagged proteins and is
      likely to have the greatest benefit for proteins that tend to aggregate when
      refolded by dilution.

PMID- 16889398
TI  - Growth of human keratinocytes and fibroblasts on bacterial cellulose film.
AB  - Thin films of bacterial cellulose (BC) from a nata de coco culture system were
      developed, characterized, and investigated for the growth of human keratinocytes
      and fibroblasts. The average pore diameter and total surface area of the dried BC
      films estimated by BET were 224 A and 12.62 m(2)/g, respectively. With an film
      thickness of 0.12 mm, the average tensile strength and break strain of the dried
      films were 5.21 MPa and 3.75%, whereas those of the wet films were 1.56 MPa and
      8.00%, respectively. The water absorption capacity of air-dried film was 5.09 g
      water/g dried films. For uses in the therapy of skin wounds, the potential
      biological mechanism of action of BC film was evaluated by using human
      keratinocytes and fibroblasts. Our results were the first direct demonstration
      that BC film supported the growth, spreading, and migration of human
      keratinocytes but not those of human fibroblasts. Expressions of E-cadherin and
      the alpha-3 chain of laminin confirmed the phenotype of human keratinocytes on BC
      film.

PMID- 16889399
TI  - A flow cytometric assay for screening improved heterologous protein secretion in
      yeast.
AB  - Selection of highly productive hosts for protein expression is a significant
      component of bioprocess design. As an alternative to traditional plate, halo, and
      suppression-based screens, we describe a high-throughput, flow cytometric assay,
      the Cell Surface Secretion Assay (CeSSA), that can be used to select for improved
      heterologous protein secretion from a population of S. cerevisiae mutants. A
      ligand is covalently attached to the cell surface via a PEG linker, and as cells
      secrete a protein that binds the tethered ligand, the protein is captured on the
      surface where it can be labeled and the cells sorted using flow cytometry. This
      report describes three different protein/ligand interactions that have been
      demonstrated with this system. Single-pass sorting enrichments from 23- to 54
      fold have been validated in the separation of a 3-fold higher secretor from a
      background population of wild-type secretors making this system applicable to
      large library screening (10(8) clones). A mathematical model was developed to
      improve the parameters of the assay further. The model was validated with time
      course data and predicts an optimal screening window. The model also predicts a
      60-fold enrichment rate for the validation experiment described above. With the
      development of this selection system, limitations presented by traditional,
      particularly plate-based, secretion assays can be overcome so that a larger
      search space can be examined under conditions closer to the growth physiology
      experienced by cells in fermentors.

PMID- 16889400
TI  - A heterogeneous kinetic model for the cutinase-catalyzed hydrolysis of cyclo-tris
      ethylene terephthalate.
AB  - The kinetics of enzyme-catalyzed hydrolysis of the polyester oligomer cyclo-tris
      ethylene terephthalate, commonly known as cyclic trimer, using a developmental
      cutinase is reported. The effect of substrate surface area and enzyme
      concentration, in a largely aqueous medium, on the rate of hydrolysis was
      measured via spectrophotometric measurement using high performance liquid
      chromatography (lambda 254 nm) at 60 degrees C in a glycine buffer (pH 8). The
      rate was strongly dependent on the substrate's surface characteristics. When the
      substrate surface area was relatively small and the substrate was relatively low
      in crystallinity, the reaction followed zero order kinetics, whereas a first
      order rate constant was obtained when the substrate surface area was increased
      considerably and the crystallinity was relatively high.

PMID- 16889401
TI  - Innovative modular membrane adsorber system for high-throughput downstream
      screening for protein purification.
AB  - To develop the most efficient strategy for the purification of proteins, two
      types of adsorber membrane devices with different functionalities were designed
      and tested: 8-strips and single spin columns. The most suitable type of membrane
      adsorber and the optimal chromatographic loading/elution conditions for several
      target proteins from different biological matrices could be determined
      simultaneously in microliter scale. Ion exchange (IEX), metal chelate (MC), and
      Concanavalin A (Con A) modified membrane types were tested in the devices. Bovine
      serum albumin (BSA) and lysozyme were used as model proteins for investigations
      of the binding capacity and protein recovery percentage of the 8-strip anion
      exchange and the cation exchange membrane. The isolation of His(6)-tagged
      proteins, Bgl-His and GFP-His from fermentation broth and lysate, respectively,
      was performed using an 8-strip metal chelate affinity membrane loaded with
      different metal ions. Separation behavior of a ternary protein mixture (BSA,
      lysozyme, and Bgl-His) was studied in 8-strips IEX and metal chelate membrane
      chromatography. The Con A affinity devices were developed on the basis of metal
      chelate membrane spin columns loaded with Cu(2+) ions and investigated using
      glucose oxidase (GOD) as model protein. In summary, the advantages of the
      membrane adsorber technology, such as fast processing and easy scale-up, were
      utilized. The devices made it possible to load the membrane directly with
      preclarified fermentation broth or cell lysate and separate the protein of
      interest often in a single step.

PMID- 16889402
TI  - Linear DNA low efficiency transfection by liposome can be improved by the use of
      cationic lipid as charge neutralizer.
AB  - A plasmid expressing the beta-galactosidase enzyme was used to transfect Vero
      cells in order to evaluate the efficiency of a liposome-mediated transfection by
      circular and linear DNA. The results obtained showed a low rate of transfection
      by linear DNA:liposome complexes. To explore whether the structure of the
      complexes was interfering with the transfection, atomic force microscopy (AFM)
      was used. It has confirmed the difference between the linear and circular
      condensates: whereas the circular DNA:liposome complexes presented compact
      spherical or cylindrical structures of about 100-800 nm, the linear DNA showed
      pearl necklace-like structures, with pearls varying from 250 to 400 nm. On the
      basis of the theory proposed by Kuhn et al. (1999), low concentrations of
      cationic amphihile were used to neutralize or reverse the DNA charge in order to
      improve the transfection efficiency of the linear DNA. Using this method, we were
      able to obtain the expression of the transgene without an associated toxicity
      observed with the linear DNA liposome delivery.

PMID- 16889403
TI  - Providing an oxidizing environment for the cell-free expression of disulfide
      containing proteins by exhausting the reducing activity of Escherichia coli S30
      extract.
AB  - We developed a novel method of producing proteins containing multiple disulfide
      bonds in a cell-free protein synthesis system. To provide an optimized redox
      potential during the synthesis of truncated plasminogen activator (rPA), we
      pretreated the E. coli S30 extract with an excess amount of oxidized glutathione
      based on the anticipation that the reducing potential of the S30 extract would be
      exhausted through the reduction of the oxidized glutathione molecules. As
      expected, it was found that the reducing activity of the S30 extract was
      remarkably decreased through the pretreatment, and active rPA was produced when
      the pretreated S30 extract was used after removing the residual glutathione
      molecules. In particular, compared to the method involving the iodoacetamide
      treatment of S30 extract, the present protocol was effective in producing active
      rPA during the batch reaction of cell-free protein synthesis.

PMID- 16889404
TI  - Protein intrinsic disorder and human papillomaviruses: increased amount of
      disorder in E6 and E7 oncoproteins from high risk HPVs.
AB  - It is recognized now that many functional proteins or their long segments are
      devoid of stable secondary and/or tertiary structure and exist instead as very
      dynamic ensembles of conformations. They are known by different names including
      natively unfolded, intrinsically disordered, intrinsically unstructured,
      rheomorphic, pliable, and different combinations thereof. Many important
      functions and activities have been associated with these intrinsically disordered
      proteins (IDPs), including molecular recognition, signaling, and regulation. It
      is also believed that disorder of these proteins allows function to be readily
      modified through phosphorylation, acetylation, ubiquitination, hydroxylation, and
      proteolysis. Bioinformatics analysis revealed that IDPs comprise a large fraction
      of different proteomes. Furthermore, it is established that the intrinsic
      disorder is relatively abundant among cancer-related and other disease-related
      proteins and IDPs play a number of key roles in oncogenesis. There are more than
      100 different types of human papillomaviruses (HPVs), which are the causative
      agents of benign papillomas/warts, and cofactors in the development of carcinomas
      of the genital tract, head and neck, and epidermis. With respect to their
      association with cancer, HPVs are grouped into two classes, known as low (e.g.,
      HPV-6 and HPV-11) and high-risk (e.g., HPV-16 and HPV-18) types. The entire
      proteome of HPV includes six nonstructural proteins [E1, E2, E4, E5, E6, and E7
      (the latter two are known to function as oncoproteins in the high-risk HPVs)] and
      two structural proteins (L1 and L2). To understand whether intrinsic disorder
      plays a role in the oncogenic potential of different HPV types, we have performed
      a detailed bioinformatics analysis of proteomes of high-risk and low-risk HPVs
      with the major focus on E6 and E7 oncoproteins. The results of this analysis are
      consistent with the conclusion that high-risk HPVs are characterized by the
      increased amount of intrinsic disorder in transforming proteins E6 and E7.

PMID- 16889405
TI  - Using annotated peptide mass spectrum libraries for protein identification.
AB  - A system for creating a library of tandem mass spectra annotated with
      corresponding peptide sequences was described. This system was based on the
      annotated spectra currently available in the Global Proteome Machine Database
      (GPMDB). The library spectra were created by averaging together spectra that were
      annotated with the same peptide sequence, sequence modifications, and parent ion
      charge. The library was constructed so that experimental peptide tandem mass
      spectra could be compared with those in the library, resulting in a peptide
      sequence identification based on scoring the similarity of the experimental
      spectrum with the contents of the library. A software implementation that
      performs this type of library search was constructed and successfully used to
      obtain sequence identifications. The annotated tandem mass spectrum libraries for
      the Homo sapiens, Mus musculus, and Saccharomyces cerevisiae proteomes and search
      software were made available for download and use by other groups.

PMID- 16889406
TI  - PPARalpha and PPARgamma regulation of liver and adipose proteins in obese and
      dyslipidemic rodents.
AB  - Zucker fatty rats and ob/ob mice are both frequently used hyperlipidemic and
      insulin-resistant spontaneous genetic models of obesity. We used them to study
      the effect of PPAR agonists on the protein-expression level in liver and white
      adipose tissue. PPARalpha-agonist treatments of the rats resulted in that 27% of
      the quantified hepatic proteins were altered; implicating pronounced peroxisome
      proliferation and increase in capacity for beta-oxidation of fatty acids although
      no correction of plasma triglycerides were obtained. On treatment with PPARgamma
      agonists, adipose proteins were regulated to a much larger extent in the rats
      compared to mice, 18% and 2%, respectively.

PMID- 16889407
TI  - Comprehensive proteomic analysis of Shigella flexneri 2a membrane proteins.
AB  - Shigella flexneri is the causative agent of most shigellosis cases in developing
      countries. We used different proteolytic enzymes to selectively shave the
      protruding proteins on the surface of purified bacterial membrane sheets or
      vesicles, and recovered peptides were subsequently identified using 2-D LC-MS/MS.
      As a result, a total of 666 proteins were unambiguously assigned, including 159
      integral membrane proteins, 35 outer membrane proteins and 114 proteins
      previously annotated as hypothetical. The former had an average grand average
      hydrophobicity score of 0.362 and were predicted to separate within a pH range of
      4.1-10.6 with molecular mass 8-148 kDa, which represents the largest validated
      set of integral membrane proteins in this organism to date. A functional
      classification revealed that a large proportion of the identified proteins were
      involved in cell envelope biogenesis and energy production and conversion. For
      the first time, this work provides a global view of the S. flexneri 2a membrane
      subproteome.

PMID- 16889408
TI  - Mass spectrometry-based study of the plasma proteome in a mouse intestinal tumor
      model.
AB  - Early detection of cancer can greatly improve prognosis. Identification of
      proteins or peptides in the circulation, at different stages of cancer, would
      greatly enhance treatment decisions. Mass spectrometry (MS) is emerging as a
      powerful tool to identify proteins from complex mixtures such as plasma that may
      help identify novel sets of markers that may be associated with the presence of
      tumors. To examine this feature we have used a genetically modified mouse model,
      Apc(Min), which develops intestinal tumors with 100% penetrance. Utilizing liquid
      chromatography-tandem mass spectrometry (LC-MS/MS), we identified total plasma
      proteome (TPP) and plasma glycoproteome (PGP) profiles in tumor-bearing mice.
      Principal component analysis (PCA) and agglomerative hierarchial clustering
      analysis revealed that these protein profiles can be used to distinguish between
      tumor-bearing Apc(Min) and wild-type control mice. Leave-one-out cross-validation
      analysis established that global TPP and global PGP profiles can be used to
      correctly predict tumor-bearing animals in 17/19 (89%) and 19/19 (100%) of cases,
      respectively. Furthermore, leave-one-out cross-validation analysis confirmed that
      the significant differentially expressed proteins from both the TPP and the PGP
      were able to correctly predict tumor-bearing animals in 19/19 (100%) of cases. A
      subset of these proteins was independently validated by antibody microarrays
      using detection by two color rolling circle amplification (TC-RCA). Analysis of
      the significant differentially expressed proteins indicated that some might
      derive from the stroma or the host response. These studies suggest that mass
      spectrometry-based approaches to examine the plasma proteome may prove to be a
      valuable method for determining the presence of intestinal tumors.

PMID- 16889409
TI  - Split-field drift tube/mass spectrometry and isotopic labeling techniques for
      determination of single amino acid polymorphisms.
AB  - A combination of split-field drift tube/mass spectrometry and isotopic labeling
      techniques is evaluated as a means of identifying single amino acid polymorphisms
      (SAAPs) in proteins. The method is demonstrated using cytochromec (equine and
      bovine) and hemoglobin (bovine and sheep). For these studies, proteins from
      different species are digested with trypsin, and the peptides are labeled at
      primary amine groups [using either a light (H(3))- or heavy (D(3))-isotopic
      reagent]. SAAP analysis is carried out by mixing the light-labeled peptides of
      one species with the heavy-labeled peptides of the other and electrospraying the
      resulting mixture into a split-field drift tube/mass spectrometer. Peptides
      having the same sequence in both species appear as doublets in the mass spectrum
      [shifted in mass-to-charge (m/z) according to the number of incorporated labels];
      additionally, these species have identical mobility distributions. Peptides
      having sequences that differ by one amino acid appear as peaks in the mass
      spectrum that are shifted in m/z according to the mass difference associated with
      the SAAP and the number of incorporated labels. The ion mobility distributions
      for these peptides (differing by only a single amino acid) can often be
      rationalized by their expected similarities or differences providing additional
      evidence that they are related. In all, 12 and 26 peptide variants (between
      species) corresponding to 5 and 11 amino acid polymorphisms have been identified
      for the cytochrome c and hemoglobin protein samples, respectively.

PMID- 16889410
TI  - Predicting eukaryotic protein subcellular location by fusing optimized evidence
      theoretic K-Nearest Neighbor classifiers.
AB  - Facing the explosion of newly generated protein sequences in the post genomic
      era, we are challenged to develop an automated method for fast and reliably
      annotating their subcellular locations. Knowledge of subcellular locations of
      proteins can provide useful hints for revealing their functions and understanding
      how they interact with each other in cellular networking. Unfortunately, it is
      both expensive and time-consuming to determine the localization of an
      uncharacterized protein in a living cell purely based on experiments. To tackle
      the challenge, a novel hybridization classifier was developed by fusing many
      basic individual classifiers through a voting system. The "engine" of these basic
      classifiers was operated by the OET-KNN (Optimized Evidence-Theoretic K-Nearest
      Neighbor) rule. As a demonstration, predictions were performed with the fusion
      classifier for proteins among the following 16 localizations: (1) cell wall, (2)
      centriole, (3) chloroplast, (4) cyanelle, (5) cytoplasm, (6) cytoskeleton, (7)
      endoplasmic reticulum, (8) extracell, (9) Golgi apparatus, (10) lysosome, (11)
      mitochondria, (12) nucleus, (13) peroxisome, (14) plasma membrane, (15) plastid,
      and (16) vacuole. To get rid of redundancy and homology bias, none of the
      proteins investigated here had >/=25% sequence identity to any other in a same
      subcellular location. The overall success rates thus obtained via the jack-knife
      cross-validation test and independent dataset test were 81.6% and 83.7%,
      respectively, which were 46 approximately 63% higher than those performed by the
      other existing methods on the same benchmark datasets. Also, it is clearly
      elucidated that the overwhelmingly high success rates obtained by the fusion
      classifier is by no means a trivial utilization of the GO annotations as prone to
      be misinterpreted because there is a huge number of proteins with given accession
      numbers and the corresponding GO numbers, but their subcellular locations are
      still unknown, and that the percentage of proteins with GO annotations indicating
      their subcellular components is even less than the percentage of proteins with
      known subcellular location annotation in the Swiss-Prot database. It is
      anticipated that the powerful fusion classifier may also become a very useful
      high throughput tool in characterizing other attributes of proteins according to
      their sequences, such as enzyme class, membrane protein type, and nuclear
      receptor subfamily, among many others. A web server, called "Euk-OET-PLoc", has
      been designed at http://202.120.37.186/bioinf/euk-oet for public to predict
      subcellular locations of eukaryotic proteins by the fusion OET-KNN classifier.

PMID- 16889411
TI  - Global analysis of protein tyrosine phosphatase activity with ultra-sensitive
      fluorescent probes.
AB  - Protein tyrosine phosphatases (PTPs) consist of a large family of enzymes known
      to play important roles in controlling virtually all aspects of cellular
      processes. However, assigning functional significance of PTPs in normal
      physiology and in diseases remains a major challenge in cell signaling. Since the
      function of a PTP is directly associated with its intrinsic activity, which is
      subject to post-translational regulation, new tools are needed to monitor the
      dynamic activities of PTPs, rather than mere abundance, on a global scale within
      the physiologically relevant environment of cells. To meet this objective, we
      report the synthesis and characterization of two rhodamine-conjugated probes that
      covalently label the active site of the PTPs in an activity-dependent manner,
      thus providing a direct readout of PTP activity and superior sensitivity,
      robustness, and quantifiability to previously reported biotinylated probes. We
      present evidence that the fluorescent probes can be used to identify new PTP
      markers and targets for potential diagnosis and treatment of human diseases. We
      also show that the fluorescent probes are capable of monitoring H(2)O(2)-mediated
      PTP inactivation, which should facilitate the study of regulated H(2)O(2)
      production as a new tier of control over tyrosine phosphorylation-dependent
      signal transduction. The ability to profile the entire PTP family on the basis of
      changes in their activity is expected to yield new functional insights into
      pathways regulated by PTPs and contribute to the discovery of PTPs as novel
      therapeutic targets.

PMID- 16889412
TI  - High-sensitivity blood-based detection of breast cancer by multi photon detection
      diagnostic proteomics.
AB  - We have developed several new methods for blood-based cancer detection by
      diagnostic proteomics. Ultrasensitive methods of immunoassay using multiphoton
      detection (IA/MPD) increase sensitivity by 200- to 1,000-fold (1 femtogram/mL).
      This has allowed the measurement of cancer biomarkers with very low
      concentrations in blood that could not be measured for full patient cohorts with
      conventional immunoassays. Sensitivity and specificity in cancer detection have
      been found to be potentiated by use of immunoassay panels which include tissue
      specific cancer biomarkers as well as cytokines and angiogenic factors. The
      ultrasensitive immunoassays revealed that patient to patient variations in the
      concentrations of individual biomarkers in blood can extend over many orders of
      magnitude (up to six) and that the distributions of biomarker concentrations over
      patient cohorts are non-Gaussian. New methods of data analysis which correlate
      abundances of multiple, different biomarkers have been developed to deal with
      such data sets. Sensitivity and specificity of about 95% have been achieved for
      blood-based detection of breast cancer in pilot studies on 250 patients and 95
      controls. Pilot studies indicate that this methodology may also allow
      differentiation of malignant breast cancer from benign lesions and can provide
      similar sensitivity and specificity for other epithelial cancers such as prostate
      cancer, ovarian cancer and melanoma. The methods developed for selection,
      application, and evaluation of very high sensitivity biomarker panels are
      expected to have general relevance for diagnostic proteomics.

PMID- 16889413
TI  - NMR metabolic profiling of Aspergillus nidulans to monitor drug and protein
      activity.
AB  - We describe a general protocol for using comparative NMR metabolomics data to
      infer in vivo efficacy, specificity and toxicity of chemical leads within a drug
      discovery program. The methodology is demonstrated using Aspergillus nidulans to
      monitor the activity of urate oxidase and orotidine-5'-phosphate decarboxylase
      and the impact of 8-azaxanthine, an inhibitor of urate oxidase. 8-azaxanthine is
      shown to inhibit A. nidulans hyphal growth by in vivo inactivation of urate
      oxidase.

PMID- 16889414
TI  - Multivariate approach to comparing whole-cell proteomes of Bacillus cereus
      indicates a biofilm-specific proteome.
AB  - Biofilm bacteria are widely held to exhibit a unique phenotype, typified by their
      increased resistance to antimicrobial agents. Numerous studies have been devoted
      to the identification of biofilm-specific genes, but surprisingly few have been
      reported to date. We compared the whole cell proteomes of 24 h old Bacillus
      cereus biofilms and the associated suspended population to exponential, transient
      and stationary phase planktonic cultures using the unbiased approach of principal
      component analysis, comparing the quantity variations of the 823 detected spots.
      The analyses support the hypothesis that biofilms of Gram positive bacteria have
      a unique pattern of gene expression. The data provides proteomic evidence for a
      new biofilm and surface influenced planktonic population which is distinct to
      both planktonic and biofilm cells.

PMID- 16889415
TI  - Probing early growth response 1 interacting proteins at the active promoter in
      osteoblast cells using oligoprecipitation and mass spectrometry.
AB  - Current advances in proteomics have allowed for a rapidly expanding integration
      of associated methodologies with more traditional molecular and biochemical
      approaches to the study of cell function. Recent studies on the role of inorganic
      phosphate have suggested this ion is a novel signaling molecule capable of
      altering the function of numerous cell types. Elevated inorganic phosphate
      generated in the extracellular microenvironment by differentiating osteoblasts
      has recently been determined to act through a largely uncharacterized mechanism
      as an important signaling molecule responsible for altering the transcription of
      various genes during osteoblast differentiation. The transcription factor, early
      growth response protein 1 (EGR1), has previously been shown to be involved in the
      early response of osteoblasts to inorganic phosphate. To elucidate the role of
      EGR1 as a potential early regulator of transcription in the inorganic phosphate
      response, an oligoprecipitation procedure was optimized to capture the DNA bound,
      transcriptionally active form of EGR1. The interacting proteins thusly captured
      were identified using mass spectrometry (MS). Proteins involved in transcription,
      RNA processing, and chromatin modification were identified by this approach. The
      combined oligoprecipitation-MS approach presented here is highly effective for
      isolating and characterizing entire transcriptional complexes in the DNA bound
      state and is broadly extendable to the identification of both known and unknown
      transcription factor protein complexes.

PMID- 16889417
TI  - Comparative proteomics in neurodegenerative and non-neurodegenerative diseases
      suggest nodal point proteins in regulatory networking.
AB  - Neurodegenerative disorders (ND) encompass clinically and genetically
      heterogeneous diseases with considerable overlap of their clinical,
      neuropathological and molecular phenotype. Various causes of neurodegeneration in
      disease may affect eventually the same proteins within protein networks. To
      identify common changes in ND, we compared brain protein changes detected by 2-D
      electrophoresis in four mouse models for ND: (i) Parkinson's disease, (ii)
      Huntington's disease, (iii) prion disease Scrapie, and (iv) a model for impaired
      synaptic transmission. To determine specificity of these changes for ND, we
      extended the scope of our investigation to three neurological conditions that do
      not result in neurodegeneration (non-ND). We detected 12 to 216 consistent
      qualitative or quantitative protein changes in individual ND and non-ND models
      when compared to controls. Up to 36% of these proteins were found to be altered
      in multiple disease states (at least three) and were therefore termed nodal point
      proteins. Alterations in alpha B-Crystallin and splicing factor 3b (subunit 4)
      occurred in at least three ND but not in non-ND. In contrast, alterations in
      peroxiredoxin 1 and 3, astrocytic phosphoprotein PEA15, complexin 2 and
      aminoacylase 1 were common to both ND and non-ND. Finally, we investigated the
      expression pattern of the nodal point proteins in three inbred mouse strains and
      found different protein abundance (expression polymorphisms) in all cases. Nodal
      point proteins showing expression polymorphisms may be candidate proteins for
      disease associated modifiers.

PMID- 16889416
TI  - Application of the accurate mass and time tag approach to the proteome analysis
      of sub-cellular fractions obtained from Rhodobacter sphaeroides 2.4.1. Aerobic
      and photosynthetic cell cultures.
AB  - The high-throughput accurate mass and time (AMT) tag proteomic approach was
      utilized to characterize the proteomes for cytoplasm, cytoplasmic membrane,
      periplasm, and outer membrane fractions from aerobic and photosynthetic cultures
      of the gram-nagtive bacterium Rhodobacter sphaeroides 2.4.1. In addition, we
      analyzed the proteins within purified chromatophore fractions that house the
      photosynthetic apparatus from photosynthetically grown cells. In total, 8,300
      peptides were identified with high confidence from at least one subcellular
      fraction from either cell culture. These peptides were derived from 1,514 genes
      or 35% percent of proteins predicted to be encoded by the genome. A significant
      number of these proteins were detected within a single subcellular fraction and
      their localization was compared to in silico predictions. However, the majority
      of proteins were observed in multiple subcellular fractions, and the most likely
      subcellular localization for these proteins was investigated using a Z-score
      analysis of estimated protein abundance along with clustering techniques. Good
      (81%) agreement was observed between the experimental results and in silico
      predictions. The AMT tag approach provides localization evidence for those
      proteins that have no predicted localization information, those annotated as
      putative proteins, and/or for those proteins annotated as hypothetical and
      conserved hypothetical.

PMID- 16889418
TI  - Detection and identification of sub-nanogram levels of protein in a nanoLC
      trypsin-MS system.
AB  - Proteomic workflows involving liquid-based protein separations are an alternative
      to gel-based protein analysis, however the trypsin digestion procedure is usually
      difficult to implement, particularly when processing low abundance proteins from
      capillary column effluent. To convert the protein to peptides for the purpose of
      identification, current protocols require several sample handling steps, and
      sample losses become an issue. In this study, we present an improved system that
      conducts reversed-phase protein chromatography and rapid on-line tryptic
      digestion requiring sub-nanogram quantities of protein. This system employs a
      novel mirror-gradient concept that allows for dynamic titration of the column
      effluent to create optimal conditions for real-time tryptic digestion. The
      purpose behind this development was to improve the limits of detection of the
      online concept, to support flow-based alternatives to gel-based proteomics and to
      simplify the characterization of low abundance proteins. Using test mixtures of
      proteins, we show that peptide mass fingerprinting with high sequence
      representation can be easily achieved at the 20 fmol level, with detection limits
      down to 5 fmol (85 pg myoglobin). Limits of identification using standard data
      dependent MS/MS experiments are as low as 10 fmol. These results suggest that the
      nanoLC-trypsin-MS/MS system could represent an alternative to the conventional
      "1D-gel to MS" proteomic strategy.

PMID- 16889419
TI  - Comparison of vacuum matrix-assisted laser desorption/ionization (MALDI) and
      atmospheric pressure MALDI (AP-MALDI) tandem mass spectrometry of 2-dimensional
      separated and trypsin-digested glomerular proteins for database search derived
      identification.
AB  - Mass spectrometric based sequencing of enzymatic generated peptides is widely
      used to obtain specific sequence tags allowing the unambiguous identification of
      proteins. In the present study, two types of desorption/ionization techniques
      combined with different modes of ion dissociation, namely vacuum matrix-assisted
      laser desorption/ionization (vMALDI) high energy collision induced dissociation
      (CID) and post-source decay (PSD) as well as atmospheric pressure (AP)-MALDI low
      energy CID, were applied for the fragmentation of singly protonated peptide ions,
      which were derived from two-dimensional separated, silver-stained and trypsin
      digested hydrophilic as well as hydrophobic glomerular proteins. Thereby, defined
      properties of the individual fragmentation pattern generated by the specified
      modes could be observed. Furthermore, the compatibility of the varying PSD and
      CID (MS/MS) data with database search derived identification using two public
      accessible search algorithms has been evaluated. The peptide sequence tag
      information obtained by PSD and high energy CID enabled in the majority of cases
      an unambiguous identification. In contrast, part of the data obtained by low
      energy CID were not assignable using similar search parameters and therefore no
      clear results were obtainable. The knowledge of the properties of available MALDI
      based fragmentation techniques presents an important factor for data
      interpretation using public accessible search algorithms and moreover for the
      identification of two-dimensional gel separated proteins.

PMID- 16889420
TI  - Metabolomics approach for enzyme discovery.
AB  - The search for novel enzymes is an important but difficult task in functional
      genomics. Here, we present a systematic method based on in vitro assays in
      combination with metabolite profiling to discover novel enzymatic activities. A
      complex mixture of metabolites is incubated with purified candidate proteins and
      the reaction mixture is subsequently profiled by capillary electrophoresis
      electrospray ionization mass spectrometry (CE-MS). Specific changes in the
      metabolite composition can directly suggest the presence of an enzymatic activity
      while subsequent identification of the compounds whose level changed specifically
      can pinpoint the actual substrate(s) and product(s) of the reaction. We first
      evaluated the method using several Escherichia coli metabolic enzymes and then
      applied it to the functional screening of uncharacterized proteins. In this
      manner, YbhA and YbiV proteins were found to display both phosphotransferase and
      phosphatase activity toward different sugars/sugar phosphates. Our approach
      should be broadly applicable and useful for enzyme discovery in any system.

PMID- 16889421
TI  - Proteomic analysis of recurrent joint inflammation in juvenile idiopathic
      arthritis.
AB  - The synovial fluid proteome in juvenile idiopathic arthritis was investigated to
      isolate joint-specific biomarkers that are expressed in patients displaying
      recurrent joint inflammation. To identify the synovial specific proteome, matched
      synovial fluid and plasma samples were subjected to protein separation by 2
      dimension electrophoresis (2DE). Forty-three protein spots, overexpressed in the
      joint, were identified. Synovial fluids from children with single-event knee
      joint inflammation were then compared with a group with recurrent knee disease.
      Nine synovial specific proteins were significantly differentially expressed in
      the recurrent group. Proteolytic fragments of collagen X, fibrin beta-chain, and
      T-cell receptor alpha-region have been identified among this protein cluster.
      Putative biomarkers, overexpressed in the joint and differentially expressed in
      children with recurrent joint inflammation, have been identified. These proteins
      may play a significant role determining the pathological state within the
      chronically inflamed joint and influence disease progression in JIA. This is the
      first study of the synovial proteome in children.

PMID- 16889422
TI  - Prevalent structural disorder in E. coli and S. cerevisiae proteomes.
AB  - Intrinsically unstructured proteins, which exist without a well-defined 3D
      structure, carry out essential functions and occur with high frequency, as
      predicted for genomes. The generality of this phenomenon, however, is questioned
      by the uncertainty of what fraction of genomes actually encodes for expressed
      proteins. Here, we used two independent bioinformatic predictors, PONDR VSL1, and
      IUPred, to demonstrate that disorder prevails in the recently characterized
      proteomes and essential proteins of E. coli and S. cerevisiae, at levels
      exceeding that estimated from the genomes. The S. cerevisiae proteome contains
      three times as much disorder as that of E. coli, with 50-60% of proteins
      containing at least one long (>30 residues) disordered segment. This evolutionary
      advance can be explained by the observation that disorder is much higher in Gene
      Ontology categories related to regulatory, as opposed to metabolic, functions,
      and also in categories unique to yeast. Thus, protein disorder is a widespread
      and functionally important phenomenon, which needs to be characterized in full
      detail for understanding complex organisms at the molecular level.

PMID- 16889423
TI  - Two-dimensional microcolumn separation platform for proteomics consisting of on
      line coupled capillary isoelectric focusing and capillary electrochromatography.
      1. Evaluation of the capillary-based two-dimensional platform with proteins,
      peptides, and human serum.
AB  - In this report, an on-line coupling of capillary isoelectric focusing (CIEF) to
      capillary electrochromatography (CEC) is developed via a nanoinjector valve for
      performing two-dimensional (2D) proteomics separation. CIEF constitutes the first
      separation dimension, while CEC operates as the second separation dimension.
      Besides the orthogonal migration mechanisms of the two capillary-based separation
      modes, which lead to a 2D system whose overall peak capacity is the product of
      the peak capacity of the individual modes, the solvent of the CIEF mode is a weak
      eluent for the reversed-phase CEC (RP-CEC) mode, thus, allowing the transferring
      of focused fractions from CIEF to CEC without inducing band broadening, and
      instead zone sharpening would result. In fact, the transferred focused protein
      fraction from the CIEF column to the CEC column will stay tightly adsorbed to the
      inlet top of the CEC column until it will be eluted and separated into its
      protein components with a hydro-organic mobile phase. The theoretical peak
      capacity of the CIEF-CEC 2D platform is estimated at n(CIEF) (= 560) x n(CEC) (=
      97) = 54 320. This peak capacity is more than needed for proteomics profiling.
      Also, only a fraction of this peak capacity is needed when looking at heart cuts
      for performing subproteomics. The 2D platform described here offers the
      convenience to generate the needed peak capacity to solve a given proteomic
      separation problem. This is facilitated by the RP-CEC dimension, which ensures
      rapid isocratic separation of proteins and peptides and rapid solvent change and
      column equilibration and avoids lengthy gradient elution. The RP-CEC column is
      based on neutral C17 monolith, which offers high separation efficiency and
      relatively high column permeability. To the best of our knowledge, the proposed
      2D platform combining CIEF and CEC is reported for the first time for proteins
      and proteomics.

PMID- 16889424
TI  - Quantitative analysis of acrylamide labeled serum proteins by LC-MS/MS.
AB  - Isotopic labeling of cysteine residues with acrylamide was previously utilized
      for relative quantitation of proteins by MALDI-TOF. Here, we explored and
      compared the application of deuterated and (13)C isotopes of acrylamide for
      quantitative proteomic analysis using LC-MS/MS and high-resolution FTICR mass
      spectrometry. The method was applied to human serum samples that were
      immunodepleted of abundant proteins. Our results show reliable quantitation of
      proteins across an abundance range that spans 5 orders of magnitude based on ion
      intensities and known protein concentration in plasma. The use of (13)C isotope
      of acrylamide had a slightly greater advantage relative to deuterated acrylamide,
      because of shifts in elution of deuterated acrylamide relative to its
      corresponding nondeuterated compound by reversed-phase chromatography. Overall,
      the use of acrylamide for differentially labeling intact proteins in complex
      mixtures, in combination with LC-MS/MS provides a robust method for quantitative
      analysis of complex proteomes.

PMID- 16889425
TI  - Selective ion tracing and MSn analysis of peptide digests from FSBA-treated
      kinases for the analysis of protein ATP-binding sites.
AB  - Kinases play a key role in many cellular processes by catalyzing the transfer of
      phosphoryl groups from ATP to a broad number of substrates, including amino acids
      on target proteins. The reagent 5'-fluorosulfonylbenzoyl-5'-adenosine (FSBA) has
      been widely used to identify ATP-binding sites in kinases since it reacts with
      nucleophilic amino acids occurring within these motifs, determining a mass
      increase of 433 Da. In this study, we present a versatile MS approach that has
      been developed to recognize labeled peptides generated after enzymatic digestion
      of FSBA-treated kinases. Using selective ion tracing and MS(2)/MS(3) experiments,
      we were able to easily identify peptides occurring at protein ATP-binding sites,
      also affording a complete characterization of the modified amino acids. This
      methodology may be used in the development of future parent ion scanning-based
      applications directed to large scale analysis of kinases within complex protein
      mixtures.

PMID- 16889426
TI  - Characterization of the Drosophila melanogaster ribosomal proteome.
AB  - We have combined high-resolution two-dimensional (2-D) gel electrophoresis with
      mass spectrometry to identifying proteins represented in a 2-D gel database of
      Drosophila melanogaster ribosomes. First, we purified ribosomes from third instar
      Drosophila larvae and constructed a high-resolution 2-D gel database containing
      58 Coomassie blue stained polypeptides. Next, we carried out preparative 2-D PAGE
      to isolate some of the polypeptides and characterize them by MALDI-TOF. Using
      this strategy we identified 52 ribosomal spots in the database, and in each case
      confirmed their identity by MALDI-TOF/TOF. The database can be used to analyze
      Minute mutants of Drosophila.

PMID- 16889427
TI  - ProteomIQ blue, a potent post-stain for the visualization and subsequent mass
      spectrometry based identification of fluorescent stained proteins on 2D-gels.
AB  - Manual spot excision for protein identification from fluorescent stained two
      dimensional (2-D) gels is hard to accomplish. Here, we explore the use of
      ProteomIQ Blue as a post-stain method for the visualization of fluorescent
      stained/labeled proteins. We show that ProteomIQ Blue post-staining is almost as
      sensitive as staining with SYPRO Ruby or cyanine dyes alone. More than 90% of the
      protein spots that are stained with the fluorescent stains are still detectable
      with ProteomIQ Blue. In protein identification by mass spectrometry, ProteomIQ
      Blue post-stained spots provide high sensitivity and high protein sequence
      coverage of the peptide mass maps in both MALDI-TOF-MS and ESI-MS/MS analyses. In
      conclusion, post-staining of fluorescent stained gels with ProteomIQ Blue
      provides a facile and a powerful method to achieve quantitative protein analysis
      as well as protein identification in the same semianalytical gel without
      requiring sophisticated/expensive robotic equipment.

PMID- 16889428
TI  - New algorithm for 15N/14N quantitation with LC-ESI-MS using an LTQ-FT mass
      spectrometer.
AB  - A new algorithm (QN) for the (15)N /(14)N quantitation of relative protein
      abundances in complex proteomic samples is described. QN takes advantage of the
      high resolution, mass accuracy and throughput of the hybrid mass spectrometer LTQ
      FT MS. Peptide quantitation is based on MS peak intensity (measured in the FT
      MS), while peptide identification is performed in the MS/MS mode (measured in the
      LTQ linear ion trap). Accuracy of the protein abundance is enhanced by a novel
      scoring procedure, allowing filtering of less reliable measurements of peptide
      abundances. The performance of QN is illustrated in the relative quantitative
      analysis of M. acetivorans C2A cultures grown with carbon monoxide vs methanol as
      substrate. Roughly 1,000 proteins were quantitated with an average CV of 9% for
      the protein abundance ratios. QN performs quantitation without manual
      intervention, does not require high processing power, and generates files
      compatible with the Guidelines for Proteomic Data Publication.

PMID- 16889429
TI  - Looking for Thom's biomarkers with proteomics.
AB  - In recent years, large numbers of putative disease biomarkers have been
      identified. Combinations of protein biomarkers have been proposed to overcome the
      lack of single, magic-bullet identifiers of disease conditions. The number of
      biomarkers in a panel must be kept small to avoid the combinatorial explosion
      that requires very large, uneconomical sample cohorts for validation. Recent
      results on high sensitivity blood-based diagnostic proteomics (Godovac
      Zimmermann, J et al., J. Proteome Res. 2006) suggest that the keys to identifying
      useful panels include judicious application of physiological knowledge to choose
      appropriate combinations of local, tissue/disease markers and global, systemic
      markers and to use very high sensitivity protein detection. Biomarkers that show
      non-Gaussian landscapes reminiscent of Rene Thom's multiple, stable-state
      landscapes seem to have the greatest predictive value for breast cancer (Godovac
      Zimmermann, J. et al., J. Proteome Res. 2006).

PMID- 16889431
TI  - Apomorphine in dopaminergic therapy.
AB  - Apomorphine is a potent molecule for the treatment of Parkinson's disease (PD).
      It can be obtained in both the R and S forms, and it is the former that is the
      therapeutically active form. Due to its structural similarity with 3,4
      dihydroxyphenethylamine, dopamine, apomorphine can function as an agonist in the
      treatment of PD as it can stimulate both the D1 and D2 receptors of the striatum.
      The clinical efficacy of apomorphine is similar to that of 3,4
      dihydroxyphenylalanine, levodopa (L-dopa), the cornerstone drug in dopaminergic
      therapy. (R)-Apomorphine is efficacious for one of the most challenging aspects
      in the management of PD, namely, managing the unpredictable "on-off" period as a
      rescue medication after oral administration of a therapeutic drug such as L-dopa.
      The effectiveness is due to its rapid control of the wearing-off period of the
      orally administered medicine. This short review will trace the progress of
      apomorphine use starting with its initial discovery and the first indications for
      which it was used, discovery of its "cure" for PD, and the studies that led to
      demonstrating its therapeutic efficacy. The key structural features of
      apomorphine responsible for its activity are illustrated along with major issues
      of chemical stability. From a drug delivery point of view, the current form of
      administration of apomorphine and some of the potential alternate methods of
      delivery are reviewed.

PMID- 16889432
TI  - Hepatocyte targeting of nucleic acid complexes and liposomes by a T7 phage p17
      peptide.
AB  - A critical step for liver-directed gene therapy is the selective targeting of
      nucleic acids to hepatocytes. We have previously discovered that the proximal
      half of the T7 phage tail fiber protein (p17) targeted intact T7 phage and
      recombinant proteins to hepatocytes in vivo. In the present study, we have
      localized the targeting activities to a 33 amino acid sequence within the p17
      coiled-coil rod domain. Given that the tail fiber domain from which the peptide
      was derived may form alpha and triple helical structures, biophysical studies (CD
      spectra and analytical ultracentrifugation) were conducted to determine the
      secondary and tertiary structures of the peptide. This peptide is able to target
      proteins, polymers, and siRNA and also particles such as DNA polyplexes and
      liposomes to hepatocytes. A variety of coupling strategies and chemistries were
      employed, thus demonstrating that this peptide is a versatile system for
      delivering cargo. The ability of this hepatocyte-targeting peptide to target DNA
      containing particles suggests that it should be useful in the development of both
      nonviral and viral vectors. However, biological function of delivered cargo has
      not been demonstrated. This was primarily due to failure of delivered cargo to
      escape the endosomes. Further studies are in progress to provide functional
      activity of delivered nucleic acids by enabling their endosomal escape.

PMID- 16889433
TI  - Intravesical antisense therapy for cystitis using TAT-peptide nucleic acid
      conjugates.
AB  - The present study investigated the potential of intravesical instillation for
      localized reduction of NGF (nerve growth factor) expression in the urinary
      bladder. Overexpression of NGF has been linked to the pathogenesis of
      interstitial cystitis (IC). A minimum free energy algorithm was used to predict
      suitable regions in mRNA of rat betaNGF, which can be targeted for an antisense
      approach. The candidate antisense oligos were evaluated for their ability to
      reduce NGF expression in vitro by cotransfecting HEK293 cells with NGF cDNA. A
      single oligonucleotide ODN sequence was chosen for testing in an acute cystitis
      model in rat induced by cyclophosphamide. Overexpression of NGF is known to
      mediate inflammation of bladder in this model. For improved stability, antisense
      ODN was replaced with antisense peptide nucleic acid (PNA) and its penetration
      into bladder was facilitated by tethering TAT peptide sequence. Rat bladders were
      instilled with either antisense or its scrambled control prior to cystitis
      induction. Cystometrograms performed on rats under urethane anaesthesia exhibited
      bladder contraction frequency that was significantly decreased in the antisense
      treated rats than rats treated with the control. NGF immunoreactivity was also
      decreased in the urothelium of the antisense treated bladders. Our findings
      demonstrate the feasibility of using TAT-PNA conjugates for intravesical
      antisense therapy.

PMID- 16889434
TI  - Solubilization of single-wall carbon nanohorns using a PEG-doxorubicin conjugate.
AB  - A procedure for dispersing oxidized single-wall carbon nanohorns (oxSWNHs) in
      aqueous solution using a polyethylene glycol-doxorubicin (PEG-DXR) conjugate is
      described. In this procedure, oxSWNHs were first incubated with PEG-DXR in
      dimethyl sulfoxide (DMSO) or N,N-dimethylformamide (DMF), two organic solvents
      with relatively high electric dipole moments, after which the solvent was
      gradually changed to an aqueous one via addition of water until the final
      concentration of DMSO or DMF reached 10%. The PEG-DXR-oxSWNH complex that was
      obtained was able to pass through dextran-based chromatographic media (Sephadex
      G25) equilibrated with water. By contrast, untreated oxSWNHs and DXR-treated or
      PEG-treated oxSWNHs were unable to penetrate the column, indicating that the PEG
      DXR conjugate endowed oxSWNHs with dispersibility in aqueous solution. In gel
      filtration experiments, the presence of free DXR had an inhibitory effect on the
      penetrability of PEG-DXR-oxSWNH complexes, which is consistent with the idea that
      PEG-DXR interacts with the surfaces of oxSWNHs via its DXR moiety. Quantitative
      analyses showed that the complex contained more than 250 mg of PEG-DXR for each
      gram of oxSWNHs. The average diameter of the dispersed complex was estimated to
      be approximately 160 nm using dynamic light scattering analysis. These results
      suggest that our method has the potential to open the way for the use of oxSWNHs
      as a clinically practical drug carrier.

PMID- 16889430
TI  - Recent advances in intravesical drug/gene delivery.
AB  - Targeting of drugs administered systemically relies on the higher affinity of
      ligands for specific receptors to obtain selectivity in drug response. However,
      achieving the same goal inside the bladder is much easier with an intelligent
      pharmaceutical approach that restricts drug effects by exploiting the pelvic
      anatomical architecture of the human body. This regional therapy involves
      placement of drugs directly into the bladder through a urethral catheter. It is
      obvious that drug administration by this route holds advantage in chemotherapy of
      superficial bladder cancer, and it has now become the most widely used treatment
      modality for this ailment. In recent years, the intravesical route has also been
      exploited either as an adjunct to an oral regimen or as a second-line treatment
      for neurogenic bladder. (Lamm, D. L.; Griffith, J. G. Semin. Urol. 1992, 10, 39
      44. Igawa, Y.; Satoh, T.; Mizusawa, H.; Seki, S.; Kato, H.; Ishizuka, O.;
      Nishizawa, O. BJU Int. 2003, 91, 637-641.) Instillation of DNA via this route
      using different vectors has been able to restrict the transgene expression in
      organs other than bladder. The present review article will discuss the
      shortcomings of the current options available for intravesical drug delivery
      (IDD) and lay a perspective for future developments in this field.

PMID- 16889436
TI  - JNK1 as a molecular target to limit cellular mortality under hypoxia.
AB  - Many pathological conditions and environmental impacts lead to a decrease in
      tissue oxygen supply and severe cellular hypoxia. This secondary hypoxia can
      disturb cellular homeostasis, limiting the efficacy of the prescribed treatment
      for the primary lesion, eventually leading to cellular and organismal death. Jun
      N-terminal kinase 1 (JNK1) plays a major role in the hypoxic cellular damage.
      Therefore, we hypothesized that suppression of JNK1 activity will decrease
      cellular mortality under hypoxia and might increase the efficacy of traditional
      treatment of many pathological conditions. These investigations are aimed at
      studying the influence of the suppression of JNK1 activity on the development of
      cellular hypoxic damage. We used antisense oligonucleotides (ASO) and small
      interfering RNA (siRNA) targeted to JNK1 mRNA to inhibit the protein synthesis.
      Experiments were carried out on a cell culture under normoxia and hypoxic
      conditions that led to the death of approximately 50% of cells. ASO or siRNA was
      delivered by neutral or cationic liposomes. Intracellular localization of ASO and
      liposomes and mechanisms of apoptosis were studied. We found that the suppression
      of JNK1 activity by liposomal antisense oligonucleotides or siRNA limits the
      caspase-dependent apoptosis signaling pathway and decreases cellular mortality
      after severe hypoxia. JNK1 protein might be an attractive target for antihypoxic
      therapy in increasing resistance to many pathological conditions and diseases,
      leading to the oxygen deficit.

PMID- 16889435
TI  - Diacyllipid micelle-based nanocarrier for magnetically guided delivery of drugs
      in photodynamic therapy.
AB  - We report the design, synthesis using nanochemistry, and characterization of a
      novel multifunctional polymeric micelle-based nanocarrier system, which
      demonstrates combined function of magnetophoretically guided drug delivery
      together with light-activated photodynamic therapy. Specifically, the nanocarrier
      consists of polymeric micelles of diacylphospholipid-poly(ethylene glycol) (PE
      PEG) coloaded with the photosensitizer drug 2-[1-hexyloxyethyl]-2-devinyl
      pyropheophorbide-a (HPPH), and magnetic Fe3O4 nanoparticles. The nanocarrier
      shows excellent stability and activity over several weeks. The physicochemical
      characterizations have been carried out by transmission electron micrography and
      optical spectroscopy. An efficient cellular uptake has been confirmed with
      confocal laser scanning microscopy. The loading efficiency of HPPH is practically
      unaffected upon coloading with the magnetic nanoparticles, and its phototoxicity
      is retained. The magnetic response of the nanocarriers was demonstrated by their
      magnetically directed delivery to tumor cells in vitro. The magnetophoretic
      control on the cellular uptake provides enhanced imaging and phototoxicity. These
      multifunctional nanocarriers demonstrate the exciting prospect offered by
      nanochemistry for targeting photodynamic therapy.

PMID- 16889437
TI  - In vivo ocular pharmacokinetics of acyclovir dipeptide ester prodrugs by
      microdialysis in rabbits.
AB  - In vivo corneal absorption of the dipeptide prodrugs of acyclovir (ACV) was
      evaluated using microdialysis in rabbits. A corneal well was placed on the cornea
      of the anesthetized New Zealand White rabbits with implanted linear probes into
      the aqueous humor. Two hundred microliters of a 1% solution of L-valine-ACV
      (VACV), glycine-valine-ACV (GVACV), valine-valine-ACV (VVACV), and valine
      tyrosine-ACV (VYACV) was placed in the corneal well and was allowed to diffuse
      for a period of 2 h, following which the drug solution was aspirated and well
      removed. Samples were collected every 20 min throughout the infusion and
      postinfusion phases and were analyzed by HPLC to obtain the aqueous humor
      concentrations. Absorption rate constants of all the compounds were found to be
      lower than the elimination rate constants. GVACV exhibited highest absorption
      rate (ka) compared with other prodrugs, but all the prodrugs showed similar
      terminal elimination rate (lambda(z)). The time of maximum absorption (Tmax) of
      ACV after administration of VACV and the dipeptide prodrugs did not vary
      significantly (p < 0.05). GVACV exhibited the highest concentration (Cmax) and
      area under curve (AUC) upon absorption (p < 0.05) compared to VACV, VVACV, and
      VYACV. Dipeptide prodrugs of ACV were absorbed through the cornea at similar
      rates but to varying extents. The dipeptide prodrug GVACV owing to its enhanced
      absorption of ACV seems to be a promising candidate for the treatment of ocular
      HSV infections.

PMID- 16889438
TI  - Cytotoxicity of organic compounds against ovarian cancer cells: a quantitative
      structure-activity relationship study.
AB  - The interest in the application of structure-activity relationships has steadily
      increased in recent decades. In the present paper, we have discussed the
      cytotoxicity of various sets of organic compounds against ovarian cancer cells by
      the formulation of a total number of 11 QSARs. Hydrophobicity is found to be one
      of the most important determinants of activity followed by steric parameters.
      Parabolic correlation with hydrophobicity is an encouraging example, where the
      optimal hydrophobicity is well-defined. We believe that this may be the
      predictive model to narrow the synthetic challenges in order to yield very
      specific OVCAR-3 inhibitors. On the basis of this model, we can predict three
      compounds that may be the next synthetic target. Cross-validation and Y
      randomization tests were used to validate all the QSAR models.

PMID- 16889439
TI  - Synthesis and biological activity of N-2,3-dihydroxypropyl-N-4-chlorobutyl
      nucleoside phosphoramidate prodrugs.
AB  - N-2,3-dihydroxypropyl-N-4-chlorobutyl phosphoramidate prodrugs of thymidine and 5
      fluoro-2'-deoxyuridine (5-FdU) 2-4 were synthesized as analogues of the known
      prodrugs 1a,b to assess the effects of the dihydroxypropyl moiety on prodrug
      activation, log P, and growth inhibitory activity in vitro. The thymidine
      analogues 2 and 3 were prepared as model compounds for kinetics and log P
      studies. 31P NMR kinetics following hydrogenolysis of 2 showed that the thymidine
      N-dihydroxypropyl phosphoramidate released thymidine monophosphate with a half
      life of 212 min under model physiologic conditions compared to approximately 2
      min for the corresponding N-methyl phosphoramidate reported previously. The
      measured log P for compound 3 was 1.1 log units lower than that of the analogous
      1b, confirming that the dihydroxypropyl group significantly decreased prodrug
      lipophilicity. The dihydroxypropyl prodrug 4 showed cell growth inhibition
      activity in the NCI 60 cell line panel similar to that of the N-methyl analogue
      1a previously reported.

PMID- 16889440
TI  - Laulimalide and synthetic laulimalide analogues are synergistic with paclitaxel
      and 2-methoxyestradiol.
AB  - Some of the most significant therapeutic leads and agents used for the treatment
      of cancer target microtubule dynamics. Paclitaxel is an exceptional example that
      is currently used for treating a wide range of tumors. New, non-taxane
      microtubule stabilizers, including several epothilones, are advancing through
      clinical trials. Laulimalide is a potent microtubule stabilizer that binds to
      tubulin at a site that does not overlap the taxane-binding site. It is active
      against paclitaxel-resistant cancer cells. Notwithstanding its therapeutic
      potential, laulimalide is relatively unstable, rearranging to a more stable but
      less active isomer. The goal of this study was to evaluate the ability of
      laulimalide and two designed laulimalide analogues, C16-C17-des-epoxy laulimalide
      (LA1) and C20-methoxy laulimalide (LA2), to inhibit cell proliferation in
      combination with other tubulin-binding and non-tubulin-binding antiproliferative
      antimitotic agents. The synthetic laulimalide analogues retain the mechanism of
      action of the natural compound but do not share its instability. We studied the
      ability of the laulimalides to act synergistically with paclitaxel, 2
      methoxyestradiol, and monastrol, an Eg5 kinesin inhibitor. The results show that
      all three of the laulimalides acted synergistically with paclitaxel and 2
      methoxyestradiol to inhibit proliferation with the analogues exhibiting
      significantly larger synergistic effects. The combination of laulimalide and
      monastrol was not synergistic and provided only additive effects. The laulimalide
      analogues LA1 and LA2 had a greater degree of synergy with both paclitaxel and 2
      methoxyestradiol than was observed with laulimalide. Our results show that the
      laulimalides together with other tubulin-binding antimitotic agents provide
      synergistic antiproliferative actions. The data are consistent with the
      previously reported ability of laulimalide and paclitaxel to act synergistically
      to polymerize tubulin in vitro. These important findings suggest that specific
      combinations of microtubule-targeting agents should be considered for clinical
      utilities as they have excellent potential to improve clinical response.

PMID- 16889441
TI  - Design of manganese porphyrin modified with mitochondrial signal peptide for a
      new antioxidant.
AB  - A new design of antioxidant, consisting of manganese (Mn) porphyrin and signal
      peptide for mitochondrial targeting, is reported. The resulting Mn-porphyrin
      oligopeptide conjugate exhibited significant superoxide dismutase (SOD) activity
      and decomposed peroxynitrite (ONOO-). The new antioxidant caused the swelling of
      isolated mitochondria. By using the pH-sensitive drug carrier for intracellular
      delivery, furthermore, the new conjugate recovered the viability of
      lipopolysaccharide (LPS)-stimulated macrophage RAW 264.7 cells. These results
      suggest that the Mn-porphyrin modified with signal peptide for mitochondrial
      targeting is promising for a new class of antioxidants.

PMID- 16889443
TI  - Pharmacotherapy for the treatment of aggressive behavior in general adult
      psychiatry: A systematic review.
AB  - OBJECTIVE: To systematically review the evidence for pharmacologic management of
      outwardly directed aggressive behavior in general adult psychiatry. DATA SOURCES:
      Literature searches in PubMed, EMBASE, PsycINFO, and Cochrane libraries from 1966
      through March 2005 were used to identify relevant studies. The keywords
      aggression, violence, anger, and hostility combined with drug therapy,
      psychotropic drugs, adrenergic beta-antagonists, anticonvulsants, anti
      depressants, antipsychotic agents, benzodiazepines, and lithium were searched.
      Furthermore, the retrieved publications were searched for additional references.
      STUDY SELECTION: All randomized controlled trials addressing pharmacotherapy for
      aggression or aggression-related symptoms were included, except studies
      addressing the "emergency situation" and studies conducted in specialized
      psychiatric or non-psychiatric settings. DATA EXTRACTION: Evidence synthesis was
      performed using the "best-evidence principle." Two authors independently
      adjudicated methodological quality and generalizability to daily clinical
      practice. DATA SYNTHESIS: Thirty-five randomized controlled trials met the
      inclusion criteria and were evaluated. On the basis of a best-evidence synthesis
      model, weak evidence for antiaggressive effects of antipsychotics, anti
      depressants, anticonvulsants, and beta-adrenergic-blocking drugs was found.
      Atypical antipsychotics appeared superior to typical antipsychotics. The use of
      various outcome measures and insufficient data reporting in the individual
      studies hampered the quantitative assessment of efficacy across studies. Further
      limitations of the available randomized controlled trials included small sample
      sizes, short study duration, and poor generalizability to daily clinical practice
      setting. CONCLUSIONS: Whereas pharmacotherapy is frequently applied in aggressive
      patients, only weak evidence of efficacy of various drug classes was found.
      Consensus about the use of aggression measurement scales in clinical trials is
      necessary for future research. Furthermore, large-scale trials with more
      naturalistic designs, as opposed to classical randomized controlled trials with
      strict inclusion and exclusion criteria, may be advisable in order to obtain
      results that are more generalizable to daily clinical practice.

PMID- 16889445
TI  - Associations between bipolar disorder and metabolic syndrome: A review.
AB  - OBJECTIVES: To examine the pathophysiologic mechanisms that may link bipolar
      disorder and metabolic syndrome and to discuss whether the consequences of
      metabolic syndrome underlie a substantive portion of the premature morbidity and
      mortality observed in persons with bipolar disorder. DATA SOURCES: A MEDLINE
      search, citing articles from 1966 onward, supplemented by a review of
      bibliographies, was conducted to identify relevant studies. Bipolar disorder,
      mood disorder, metabolic syndrome, diabetes, cardiovascular illness, and obesity
      were used as keywords. Criteria used to select studies included (1) English
      language, (2) published studies with original data in peer-reviewed journals, and
      (3) studies that confirmed the nature of the mood disorder examined. RESULTS:
      Ninety-seven studies met criteria and were reviewed for evidence of dysregulation
      in various physiologic systems. Bipolar disorder and metabolic syndrome share
      features of hormonal, immunologic, and autonomic nervous system dysregulation.
      CONCLUSION: Lifestyle features may account, in part, for the premature mortality
      observed in bipolar disorder, but the somatic correlates of the illness may also
      predispose patients to metabolic syndrome and the consequent increased risk of
      diseases such as diabetes and vascular disease.

PMID- 16889444
TI  - A 7-week, randomized, double-blind trial of olanzapine/fluoxetine combination
      versus lamotrigine in the treatment of bipolar I depression.
AB  - OBJECTIVE: Determine the efficacy and tolerability of olanzapine/fluoxetine
      combination (OFC) for treatment of acute bipolar I depression compared with
      lamotrigine. METHOD: The 7-week, acute phase of a randomized, double-blind study
      compared OFC (6/25, 6/50, 12/25, or 12/50 mg/day; N = 205) with lamotrigine
      ([LMG] titrated to 200 mg/day; N = 205) in patients with DSM-IV-diagnosed bipolar
      I disorder, depressed. The study was conducted from November 2003 to August 2004.
      RESULTS: Completion rates were similar between treatments (OFC, 66.8% vs. LMG,
      65.4%; p = .835). OFC-treated patients had significantly greater improvement than
      lamotrigine-treated patients in change from baseline across the 7-week treatment
      period on the Clinical Global Impressions-Severity of Illness scale (primary
      outcome) (p = .002, effect size = 0.26), Montgomery-Asberg Depression Rating
      Scale (MADRS) (p = .002, effect size = 0.24), and Young Mania Rating Scale total
      scores (p = .001, effect size = 0.24). Response rates did not significantly
      differ between groups when defined as > or = 50% reduction in MADRS score (OFC,
      68.8% vs. LMG, 59.7%; p = .073). Time to response was significantly shorter for
      OFC-treated patients (median days [95% CI] = OFC, 17 [14 to 22] vs. LMG, 23 [21
      to 34]; p = .010). There was a significant difference in incidence of "suicidal
      and self-injurious behavior" adverse events (OFC, 0.5% vs. LMG, 3.4%; p = .037).
      Somnolence, increased appetite, dry mouth, sedation, weight gain, and tremor
      occurred more frequently (p < .05) in OFC-treated patients than lamotrigine
      treated patients. Weight, total cholesterol, and triglyceride levels were
      significantly elevated in OFC-treated patients compared with lamotrigine-treated
      patients (all p < or = .001). CONCLUSIONS: Patients with acute bipolar I
      depression had statistically significantly greater improvement in depressive and
      manic symptoms, more treatment-emergent adverse events, greater weight gain, and
      some elevated metabolic factors with OFC than lamotrigine. Treatment differences
      were of modest size.

PMID- 16889446
TI  - Efficacy and tolerability of quetiapine in the treatment of borderline
      personality disorder: A pilot study.
AB  - OBJECTIVE: Second-generation antipsychotics with a favorable tolerability profile
      have offered new treatment options for patients with borderline personality
      disorder. Sparse data are available on the use of quetia-pine in treating this
      disorder. The aim of the present study is to investigate efficacy and
      tolerability of quetia-pine in a group of patients with borderline personality
      disorder. METHOD: Fourteen consecutive outpatients with a DSM-IV diagnosis of
      borderline personality disorder were treated for 12 weeks with open-label
      quetiapine at the dose of 200-400 mg/day. Patients were assessed at baseline,
      week 4, and week 12 with the Clinical Global Impressions (CGI) severity item, the
      Brief Psychiatric Rating Scale (BPRS), the Hamilton Rating Scale for Depression
      (HAM-D), the Hamilton Rating Scale for Anxiety (HAM-A), the Social and
      Occupational Functioning Assessment Scale (SOFAS), the Borderline Personality
      Disorder Severity Index (BPDSI), and the Barratt Impulsiveness Scale-version 11
      (BIS-11). Adverse effects were evaluated using the Dosage Record and Treatment
      Emergent Symptom Scale. Statistical analysis was performed with the ANOVA for
      repeated measures. Significant p values were < or = .05. RESULTS: Eleven patients
      completed the study. Three patients (21.4%) dropped out due to excessive
      somnolence or noncompliance. The mean +/- SD dose of quetia-pine was 309.09 +/-
      83.12 mg/day. A significant change was found for the scores of the following
      scales: CGI severity item, BPRS, HAM-A, SOFAS, BPDSI total score, BPDSI items
      "impulsivity" and "outbursts of anger," and BIS-11. Common adverse effects were
      mild-to-moderate somnolence, dry mouth, and dizziness. CONCLUSION: Initial data
      suggest that quetiapine is efficacious and well tolerated in treating patients
      who have borderline personality disorder, particularly when
      impulsiveness/aggressiveness-related symptoms are prominent. At the moment, no
      reliable comparison is available in the literature. Double-blind controlled
      trials are needed to verify these findings.

PMID- 16889447
TI  - Evaluation of an interchangeability switch in patients treated with clozapine: A
      retrospective review.
AB  - OBJECTIVE: To report the findings of a switch from brand-name to generic
      clozapine in a Canadian outpatient population. METHOD: The medical records of 58
      outpatients diagnosed with schizophrenia and other psychotic disorders and
      stabilized on brand-name clozapine therapy were reviewed retrospectively.
      Patients were switched from brand-name to generic clozapine on their next
      dispensing supply after September 29, 2003. Data regarding clozapine dose
      regimens, physicians' visits, hospitalizations, and adverse events were collected
      from the patients' charts for the 6 months preceding and the 6 months after the
      switch from brand-name to generic clozapine. Relevant measurement changes in
      those data associated with the switch are evaluated. RESULTS: No significant
      changes in dose, number of physician's visits, or hospitalization rates were
      observed as a consequence of the switch from brand-name to generic clozapine. In
      addition, there were no reported increases in the frequency of the most common
      adverse events, including decreases in white blood cell counts. None of the
      patients received a "nonrechallengeable" status, and no discontinuation of
      clozapine therapy occurred for any reason (toxicity or treatment failure) in the
      6 months after the formulation switch. CONCLUSION: In the current outpatient
      population, retrospective evaluation of the conversion from brand-name clozapine
      to the first generic alternative available on the Canadian market did not reveal
      any significant treatment changes.

PMID- 16889448
TI  - Risk of diabetes mellitus associated with atypical antipsychotic use among
      patients with bipolar disorder: A retrospective, population-based, case-control
      study.
AB  - BACKGROUND: Drug-induced diabetes onset has not been adequately quantified in
      patients with bipolar disorder, although atypical antipsychotics have been widely
      used as new mood stabilizers. OBJECTIVES: To quantify the association between
      atypical antipsychotics and diabetes mellitus. METHOD: A retrospective,
      population-based, case-control study was conducted using the medical claims
      database from U.S. managed care organizations from January 1, 1998, to December
      31, 2002. Nine hundred twenty incident cases of diabetes were matched with 5258
      controls by age, sex, and bipolar index month and year. Diabetes cases were
      identified by either diagnosis of ICD-9 codes or diabetic medications. Patients
      with diabetes had a minimum 3-month exposure to any medications or at least 3
      prescriptions for their bipolar or comorbidity treatment. Cox proportional hazard
      regression was conducted to assess the risk of diabetes associated with
      antipsychotic use. RESULTS: Of 920 cases, 41% received atypical antipsychotics
      (e.g., olanzapine, risperidone, quetiapine, ziprasidone, clozapine) and 34%
      received conventional antipsychotics. Compared to patients receiving conventional
      antipsychotics, the risk of diabetes was greatest among patients taking clozapine
      (hazard ratio [HR] = 7.0, 95% confidence interval [CI] = 1.7 to 28.9),
      risperidone (HR = 3.4, 95% CI = 2.8 to 4.2), olanzapine (HR = 3.2, 95% CI = 2.7
      to 3.8), and quetiapine (HR = 1.8, 95% CI =1.4 to 2.4), with controlling
      covariates of age; sex; duration of follow-up; use of lithium, anticonvulsants,
      antidepressants, or concomitant drugs; and psychiatric and medical comorbidities.
      CONCLUSION: Development or exacerbation of diabetes mellitus is associated with
      antipsychotic use in bipolar patients. Metabolic complications are a major issue
      in patients receiving antipsychotic therapy. Thus, the propensity of an
      antipsychotic to induce diabetes should be a consideration when selecting an
      agent for patients with bipolar disorder.

PMID- 16889449
TI  - Prevalence, correlates, and comorbidity of nonmedical prescription drug use and
      drug use disorders in the United States: Results of the National Epidemiologic
      Survey on Alcohol and Related Conditions.
AB  - OBJECTIVE: To present national data on the prevalence, correlates, and
      comorbidity of nonmedical prescription drug use and drug use disorders for
      sedatives, tranquilizers, opioids, and amphetamines. METHOD: Data were derived
      from the National Epidemiologic Survey on Alcohol and Related Conditions
      (NESARC), a face-to-face nationally representative survey of 43,093 adults
      conducted during 2001 and 2002. RESULTS: Lifetime prevalences of nonmedical use
      of sedatives, tranquilizers, opioids, and amphetamines were 4.1%, 3.4%, 4.7%, and
      4.7%, respectively. Corresponding rates of abuse and/or dependence on these
      substances were 1.1%, 1.0%, 1.4%, and 2.0%. The odds of nonmedical prescription
      drug use and drug use disorders were generally greater among men, Native
      Americans, young and middle-aged, those who were widowed/ separated/divorced or
      never married, and those residing in the West. Abuse/dependence liability was
      greatest for amphetamines, and nonmedical prescription drug use disorders were
      highly comorbid with other Axis I and II disorders. The majority of individuals
      with non-medical prescription drug use disorders never received treatment.
      CONCLUSIONS: Nonmedical prescription drug use and disorders are pervasive in the
      U.S. population and highly comorbid with other psychiatric disorders. Native
      Americans had significantly greater rates of nonmedical prescription drug use and
      drug use disorders, highlighting the need for culturally-sensitive prevention and
      intervention programs. Unprecedented comorbidity between nonmedical prescription
      drug use disorders and between nonmedical prescription drug use disorders and
      illicit drug use disorders suggests that the typical individual abusing or
      dependent on these drugs obtained them illegally, rather than through a
      physician. Amphetamines had the greatest abuse/dependence liability, and recent
      increases in the potency of illegally manufactured amphetamines may portend an
      epidemic in the youngest NESARC cohort.

PMID- 16889450
TI  - Association between the accessibility to lethal methods and method-specific
      suicide rates: An ecological study in Taiwan.
AB  - OBJECTIVE: To examine the association between availability of lethal methods of
      suicide and method-specific suicide rates at the city/ county level in Taiwan.
      METHOD: Age-adjusted and age-specific suicide rates of 23 cities/counties in
      Taiwan for the years 1999 to 2003 were calculated. Partial correlation
      coefficients were used to examine cross-sectional associations between
      independent variables, i.e., proportion of agricultural population and proportion
      of households living on the sixth floor or above, and suicide rates by different
      methods (poisoning by solids/liquids, jumping, and hanging) after adjusting for
      unemployment rates and prevalence of depression. RESULTS: The partial correlation
      coefficient was 0.77 (p < .001) for proportion of agricultural population with
      solids/liquids poisoning suicide rates. It was 0.73 (p < .001) for the proportion
      of households living on the sixth floor or above with suicide rates by jumping.
      Correlations between hanging suicide rates and proportion of agricultural
      population or between hanging suicide rates and proportion of households living
      on the sixth floor or above were not significant. CONCLUSION: The results showed
      strong positive associations between access to lethal methods and method-specific
      suicide rates. Controlling the availability of pesticides and fencing high
      buildings or installing window guards may be effective measures for suicide
      prevention.

PMID- 16889451
TI  - Psychiatric disorder comorbidity and association with eating disorders in
      bariatric surgery patients: A cross-sectional study using structured interview
      based diagnosis.
AB  - OBJECTIVE: This study examined the prevalence of DSM-IV Axis I psychiatric
      disorders in severely obese bariatric surgery candidates and explored whether
      eating disorders were associated with psychiatric comorbidity. METHOD: The
      Structured Clinical Interview for DSM-IV Axis I Disorders was administered to a
      study group of 174 consecutively evaluated bariatric surgery candidates. All
      evaluations were completed between September 2002 and November 2004. RESULTS:
      Overall, 36.8% of the participants met criteria for at least one lifetime
      psychiatric disorder, with 24.1% meeting criteria for a current disorder. The
      most commonly observed lifetime psychiatric diagnoses were affective disorders
      (22.4%), anxiety disorders (15.5%), and eating disorders (13.8%). Participants
      with eating disorders were significantly more likely than those without eating
      disorders to meet criteria for psychiatric disorders overall (66.7% vs. 26.7%)
      and specifically for anxiety disorders (45.8% vs. 10.7%). CONCLUSIONS:
      Psychiatric disorders are not uncommon among severely obese patients who present
      for bariatric surgery. The observed prevalence rates based on structured
      diagnostic interviews are lower than previously reported based on questionnaire,
      clinical, and chart review methods but are similar to those reported for
      nationally representative samples. Among bariatric surgery candidates, the
      presence of eating disorders is associated with higher rates of other psychiatric
      disorders. The findings highlight the importance of systematic diagnostic
      assessment using a structured diagnostic interview for determining the full
      spectrum of Axis I disorders.

PMID- 16889452
TI  - Single modality versus dual modality treatment for trichotillomania: sertraline,
      behavioral therapy, or both?
AB  - BACKGROUND: Trichotillomania is a psychiatric condition characterized by chronic
      hair pulling. Both cognitive behavioral therapy (CBT) and the selective serotonin
      reuptake inhibitors (SSRIs) have shown promise in the treatment of
      trichotillomania, with comparison studies favoring CBT over pharmacotherapy.
      However, no randomized, controlled studies to date have compared the efficacy of
      individual SSRI or CBT treatment to the combination of both treatment modalities.
      METHOD: In this study, which ran from February 2000 through April 2003, subjects
      who met DSM-IV criteria for trichotillomania were randomly assigned to treatment
      with sertraline or placebo in a double-blind study design. Following 12 weeks of
      active pharmacotherapy, subjects not demonstrating significant trichotillomania
      symptom improvement had habit reversal training (HRT) added to their treatment
      regimen. Primary outcome measures were the Hair Pulling Scale and the Clinical
      Global Impressions scale. RESULTS: Thirteen subjects completing the 22-week study
      received single modality treatment of either sertraline or HRT, and 11 received
      both modalities of treatment. Trichotillomania symptoms in both groups improved,
      although the dual modality treatment group demonstrated larger gains and were
      much more likely to reach responder status at final evaluation. CONCLUSION: These
      results suggest that the combination of sertraline and HRT may be more
      efficacious in the treatment of trichotillomania than either approach alone.

PMID- 16889453
TI  - Comparison of quetiapine and risperidone in the treatment of schizophrenia: A
      randomized, double-blind, flexible-dose, 8-week study.
AB  - OBJECTIVE: To compare the efficacy and tolerability of quetiapine and risperidone
      in the treatment of schizophrenia. METHOD: In this 8-week, double-blind,
      multicenter, flexible-dose study, patients with schizophrenia (DSM-IV diagnosis)
      were randomly assigned to quetiapine (200-800 mg/day) or risperidone (2-8
      mg/day). The primary hypothesis was that quetiapine was not inferior to
      risperidone. The primary efficacy measure was change from baseline in Positive
      and Negative Syndrome Scale (PANSS) total scores; secondary outcomes included
      response rate (> or = 40% reduction in PANSS scores), Clinical Global Impression
      Change (CGI-C), and cognitive and social functioning. Tolerability assessments
      included treatment-emergent adverse events and changes in weight, glucose, and
      prolactin. Patients were recruited from June 2001 to September 2002. RESULTS:
      Patients (N = 673) were randomly assigned to quetiapine (N = 338, mean dose = 525
      mg/day) or risperidone (N = 335, mean dose = 5.2 mg/day). The primary analysis
      demonstrated noninferiority between treatments (p < .05). Improvements with both
      treatments were comparable on PANSS total, negative, and general psychopathology
      subscales. Risperidone-treated patients had a significantly (p = .03) greater
      improvement in PANSS positive subscale score among all patients, but not among
      completers. Improvements in PANSS response rates, CGI-C, and cognitive function
      were similar between treatment groups. Changes in serum glucose and weight were
      minimal and comparable. The rate of extrapyramidal symptom (EPS)-related adverse
      events was significantly higher with risperidone (22%) than quetiapine (13%; p <
      .01). Somnolence was more common with quetiapine (26%) than risperidone (20%; p =
      .04). Prolactin levels increased with risperidone (+35.5 ng/mL), but decreased
      with quetiapine (-11.5 ng/mL; p < .001). CONCLUSIONS: Quetiapine and risperidone
      had broadly comparable clinical efficacy. Both agents improved cognitive and
      social functioning, and neither had a clinically significant effect on weight or
      glucose. Somnolence was more common with quetiapine; EPS and elevated prolactin
      rates were significantly higher with risperidone.

PMID- 16889454
TI  - Preventing depression after stroke: Results from a randomized placebo-controlled
      trial.
AB  - OBJECTIVE: We designed this study to determine whether the daily treatment of
      nondepressed acute stroke patients with sertraline reduced the incidence of
      depression at follow-up. METHOD: 111 patients with recent stroke (< 2 weeks;
      International Classification of Diseases, Tenth Revision criteria) were randomly
      assigned to treatment with placebo (N = 56) and sertraline (N = 55, 50 mg once
      daily) in this double-blind, placebo-controlled 24-week clinical trial. Subjects
      were recruited from the 2 largest teaching hospitals of Western Australia between
      June 2002 and June 2004. The primary endpoint of interest was development of
      clinically significant depressive symptoms as assessed by a Hospital Anxiety and
      Depression Scale-depression subscale score of 8 or above, or as diagnosed by the
      treating physician during 24 weeks. RESULTS: There was no significant difference
      in the incidence of depressive symptoms during 24 weeks of treatment (16.7%
      [8/48] sertraline vs. 21.6% [11/51] placebo, rate ratio = 0.8, 95% CI = 0.3 to
      2.1, p = .590). The trial medication was discontinued by 51.8% (29/56) of
      patients assigned placebo and 47.3% (26/55) assigned sertraline (p = .634), most
      often because of perceived side effects or because the treating physician
      introduced an antidepressant medication. CONCLUSIONS: Twenty-four-week treatment
      with 50 mg of sertraline once daily initiated within 2 weeks of onset of acute
      stroke is not a significantly more effective strategy to prevent 6-month
      depression than usual care plus placebo among nondepressed stroke patients. New
      pharmacologic and nonpharmacologic strategies need to be developed to reduce the
      health and financial burden associated with depression after stroke.

PMID- 16889455
TI  - Risperidone-induced hyperprolactinemia in adolescents: A case series.
AB  - OBJECTIVE: To study the effect of risperidone on prolactin levels in 3 adolescent
      patients. METHOD: This is a case study of 3 adolescent patients with DSM-IV
      diagnosis of schizophreni-form disorder, major depressive disorder with psychotic
      features, or chronic undifferentiated schizophrenia who were treated in inpatient
      and outpatient psychiatric settings with risperidone. Patients developed
      hyperprolactinemia with clinical symptoms. Risperidone was discontinued gradually
      over 2 weeks, and patients were treated with other atypical antipsychotics.
      RESULTS: Prolactin levels returned to normal, and clinical symptoms of
      hyperprolactinemia resolved in all 3 patients after 2 weeks of tapering and
      discontinuation of risperidone. CONCLUSION: Hyperprolactinemia can be a
      troublesome side effect with potentially serious complications. It is being
      increasingly reported in younger patients treated with risperidone. Recognition
      and treatment of this condition including switching to a prolactin-sparing agent
      are important to prevent this complication.

PMID- 16889456
TI  - A prospective study of risk factors for nonadherence with antipsychotic
      medication in the treatment of schizophrenia.
AB  - OBJECTIVES: This study aimed to prospectively identify the best single predictor
      and the best set of predictors of risk for nonadherence with anti-psychotic
      medication in the treatment of patients with schizophrenia. METHOD: We used data
      from 1579 patients in a 3-year, prospective, naturalistic, nonrandomized,
      multisite study of schizophrenia patients conducted from July 1997 to September
      2003 (U.S. Schizophrenia Care and Assessment Program). Adherence with any oral
      antipsychotic medication was assessed using patient-reported medication adherence
      and an indirect adherence measure based on medical record prescription
      information. Patients who reported poor medication adherence or had a medication
      possession ratio < or = 80% (percentage of days with prescriptions for any oral
      antipsychotic) during the first year after enrollment were defined as nonadherent
      (N = 296, 18.8%). Thirty-nine previously reported potential risk factors of
      nonadherence with antipsychotic medication were assessed at enrollment with valid
      and reliable measures. Risk factors represented patient-, environment-, and
      treatment-related domains, including sociodemographics, symptom severity,
      substance use, threat to safety of self and others, other illness-related
      factors, need for supervision, medication-related adverse events, and prior
      medication-utilization patterns. RESULTS: The best single predictor of future
      nonadherence was nonadherence during the 6 months prior to enrollment (odds ratio
      = 4.1, 95% confidence interval = 3.1 to 5.6, p < .001). The best set of
      predictors of nonadherence, ordered by strength of association, included prior
      non-adherence, recent illicit drug use, recent alcohol use, prior treatment with
      antidepressants, and greater patient-reported, medication-related cognitive
      impairment. CONCLUSION: Nonadherence with antipsychotic medication is associated
      with a well-defined set of risk factors that can be used to identify patients who
      are predisposed to poor adherence.

PMID- 16889457
TI  - Using data mining to explore complex clinical decisions: A study of
      hospitalization after a suicide attempt.
AB  - BACKGROUND: Medical education is moving toward developing guidelines using the
      evidence-based approach; however, controlled data are missing for answering
      complex treatment decisions such as those made during suicide attempts. A new set
      of statistical techniques called data mining (or machine learning) is being used
      by different industries to explore complex databases and can be used to explore
      large clinical databases. METHOD: The study goal was to reanalyze, using data
      mining techniques, a published study of which variables predicted psychiatrists'
      decisions to hospitalize in 509 suicide attempters over the age of 18 years who
      were assessed in the emergency department. Patients were recruited for the study
      between 1996 and 1998. Traditional multivariate statistics were compared with
      data mining techniques to determine variables predicting hospitalization.
      RESULTS: Five analyses done by psychiatric researchers using traditional
      statistical techniques classified 72% to 88% of patients correctly. The model
      developed by researchers with no psychiatric knowledge and employing data mining
      techniques used 5 variables (drug consumption during the attempt, relief that the
      attempt was not effective, lack of family support, being a housewife, and family
      history of suicide attempts) and classified 99% of patients correctly (99%
      sensitivity and 100% specificity). CONCLUSIONS: This reanalysis of a published
      study fundamentally tries to make the point that these new multivariate
      techniques, called data mining, can be used to study large clinical databases in
      psychiatry. Data mining techniques may be used to explore important treatment
      questions and outcomes in large clinical databases and to help develop guidelines
      for problems where controlled data are difficult to obtain. New opportunities for
      good clinical research may be developed by using data mining analyses.

PMID- 16889458
TI  - A randomized clinical trial of cognitive-behavioral group therapy and sertraline
      in the treatment of obsessive-compulsive disorder.
AB  - BACKGROUND: Cognitive-behavioral group therapy (CBGT) and serotonin reuptake
      inhibitors have proven efficacy in reducing symptoms of obsessive-compulsive
      disorder (OCD). There is no consensus about which of these forms of treatment is
      more effective. This study was conducted to evaluate the efficacy of CBGT as
      compared to that of sertraline in reducing OCD symptoms. METHOD: Fifty-six
      outpatients with an OCD diagnosis, according to DSM-IV criteria, participated in
      the randomized clinical trial: 28 took 100 mg/day of sertraline and 28 underwent
      CBGT for 12 weeks. Efficacy of treatments was rated according to the reduction in
      scores on the Yale-Brown Obsessive Compulsive Scale (YBOCS) and the Clinical
      Global Impressions-Severity of Illness scale. The trial was performed in 4
      successive periods from March 2002 to December 2003. RESULTS: Both treatments
      were effective, although patients treated with CBGT obtained a mean YBOCS
      reduction of symptoms of 44%, while those treated with sertraline obtained only a
      28% reduction (p = .033). Cognitive-behavioral group therapy was also
      significantly more effective in reducing the intensity of compulsions (p = .030).
      Further, 8 patients (32%) treated with CBGT presented a complete remission of OCD
      symptoms (YBOCS score < or = 8) as compared to only 1 patient (4%) among those
      who received sertraline (p = .023). CONCLUSION: Cognitive-behavioral group
      therapy and sertraline have shown to be effective in reducing OCD symptoms.
      Nevertheless, the rate of symptom reduction, intensity reduction of compulsions,
      and percentage of patients who obtained full remission were significantly higher
      in patients treated with CBGT.

PMID- 16889463
TI  - Resilience in the aftermath of terrorism and during warzone exposure: Is it
      religiousness or is it number of blood relatives?

PMID- 16889464
TI  - Facial hyperhidrosis-induced social fear alleviated with topiramate.

PMID- 16889465
TI  - Tolerability of high-dose aripiprazole in treatment-refractory schizophrenic
      patients.

PMID- 16889466
TI  - Levetiracetam-induced depression in a healthy adult.

PMID- 16889467
TI  - Risperidone and lamotrigine: no evidence of a drug interaction.

PMID- 16889468
TI  - The use and performance of BioSand filters in the Artibonite Valley of Haiti: a
      field study of 107 households.
AB  - INTRODUCTION: Approximately one billion people world-wide lack access to adequate
      amounts of safe water. Most are in developing countries, especially in rapidly
      expanding urban fringes, poor rural areas, and indigenous communities. METHODS:
      In February and March 2005, a field study of 107 households was conducted to
      evaluate the use and performance of the Manz BioSand filter in the Artibonite
      Valley of Haiti. Approximately 2000 filters had been installed in this area over
      the preceding 5 years by the staff in Community Development at Hospital Albert
      Schweitzer, Deschappelle, Haiti. Interviews, observations, and water samplings
      were carried-out by two teams of Haitian enumerators, each consisting of a nurse
      and a filter technician. Water analyses were performed by Haitian lab technicians
      using the membrane filtration method to determine Escherichia coli counts. The
      enumerators and the lab technicians completed a 2 week training program before
      beginning the study; they worked under the direct supervision of the primary
      investigator. Laboratory quality was monitored by running 10% blank and 10%
      duplicate samples. RESULTS: The households contained an average of 5.4 persons.
      Filters had been in use for an average of 2.5 years, and participants were
      generally satisfied with their filter's performance. Shallow, hand-dug wells
      provided the only source of water for 61% of the households, with 26% using water
      piped from springs or deep wells, and 13% having access to both. Only 3% had
      plumbing in their homes. Source water from shallow wells contained an average of
      234 E. coli cfu/100 mL. Piped sources averaged 195 E. coli cfu/100 mL. Of the
      source water samples 26% contained 0-10 E. coli cfu/100 mL. Of the filtered water
      samples 97% contained 0-10 E. coli cfu/100 mL (80% with 0 cfu/100 mL, and 17%
      with 1-10 cfu/100 mL). Overall bacterial removal efficiency for the filters was
      calculated to be 98.5%. Turbidity decreased from an average of 6.2 NTU in source
      water samples to 0.9 NTU in the filtered water. None of the households treated
      the water after filtering; 91% used the filtered water only for drinking. No
      problems related to filter construction were observed; 13% were found to have
      significantly decreased flow rates (all restored by cleaning the filter).
      Recontamination was found to occur, with only 3% of the samples from the filters'
      spouts containing >10 E. coli cfu/100 mL and 22% of the stored filtered water
      samples at point-of-use containing >10 cfu/100 mL. CONCLUSION: The Manz BioSand
      filters are an attractive option for supplying water treatment to family units in
      rural areas of poorly developed countries.

PMID- 16889469
TI  - Building bridges with decision-makers: rules for rural and remote health
      researchers.
AB  - CONTEXT: Until recently, rural and remote health researchers have undertaken
      predominantly investigator-driven research. In Canada and elsewhere, major health
      research funding agencies have begun to expect researchers to incorporate into
      funding proposals, a well-developed plan for sharing research findings with
      decision-makers, those who can incorporate relevant findings into clinical
      practice, programs and services. ISSUE: The research arising from the interests
      of investigators, although frequently relevant to communities, too often has
      resulted in data extraction that parallels resource extraction from resource
      based rural or remote communities. Such research can result in non-usable
      findings, and in the non-use of research findings by decision-makers. LESSONS
      LEARNED: In order that useful and usable knowledge is created, bridges need to be
      built between researchers and decision-makers. Six 'rules for researchers' are
      proposed to help build bridges with decision-makers: Rule 1. Engage the right
      decision-makers; Rule 2. Determine what's in it for you and for them; Rule 3.
      Develop a sustained relationship; Rule 4. Live in their world once in a while;
      Rule 5. Think of doing research differently; Rule 6. Build integrative research
      infrastructures.

PMID- 16889470
TI  - Unraveling adaptation and mutual inhibition in perceptual rivalry.
AB  - When the visual system is confronted with incompatible images in the same part of
      the visual field, the conscious percept switches back and forth between the
      rivaling stimuli. Such spontaneous flips provide important clues to the neuronal
      basis for visual awareness. The general idea is that two representations compete
      for dominance in a process of mutual inhibition, in which adaptation shifts the
      balance to and fro. The inherent nonlinear nature of the rivalrous flip-flop and
      its stochastic behavior, however, made it impossible to disentangle inhibition
      and adaptation. Here we report a general method to measure the time course, and
      asymmetries, of mechanisms involved in perceptual rivalry. Supported by model
      simulations, we show the dynamics of opponent interactions between mutual
      inhibition and adaptation. The findings not only provide new insight into the
      mechanism underlying rivalry but also offer new opportunities to study and
      compare a wide range of bistable processes in the brain and their relation to
      visual awareness.

PMID- 16889471
TI  - The receptive field and internal noise for position acuity change with feature
      separation.
AB  - Humans are exquisitely sensitive to changes in relative position. A fundamental
      and long-standing question is how information for position acuity is integrated
      along the length of the target, and why visual performance deteriorates when the
      feature separation increases. To address this question, we used a target made of
      discrete samples, each subjected to binary positional noise, combined with
      reverse correlation to estimate the behavioral "receptive field" (template), and
      a novel 10-pass method to quantify the internal noise that limits position
      acuity. Our results show that human observers weigh individual parts of the
      stimulus differently and importantly, that the shape of the template changes
      markedly with feature separation. Compared to an ideal observer, human
      performance is limited by a template that becomes less efficient as feature
      separation increases and by an increase in random internal noise. Although
      systematic internal noise is thought to be one of the important components
      limiting detection thresholds, we found that systematic noise is negligible in
      our position task.

PMID- 16889472
TI  - Same calculation efficiency but different internal noise for luminance- and
      contrast-modulated stimuli detection.
AB  - There is no consensus on whether luminance-modulated (LM) and contrast-modulated
      (CM) stimuli are processed by common or separate mechanisms. To investigate this,
      the sensitivity variations to these stimuli are generally compared as a function
      of different parameters (e.g., sensitivity as a function of the spatial or
      temporal window sizes) and similar properties have been observed. The present
      study targets the sensitivity difference between LM and CM stimuli processing.
      Therefore, instead of studying the variation of sensitivity in different
      conditions, we propose to decompose the sensitivities in internal equivalent
      noise (IEN) and calculation efficiency (CE) to evaluate at which processing level
      the two mechanisms differ. For each stimulus type, the IEN and CE of four
      observers were evaluated using three different carriers (plaid, checkerboard, and
      binary noise). No significant CE differences were noted in all six conditions (3
      carriers x 2 modulation types), but important differences were found between the
      IEN of the two stimulus types. These data support the hypothesis that the two
      pathways are initially separate and that the two stimuli may be treated by common
      mechanisms at a later processing stage. Based on ideal observer analysis, pre
      rectification internal noise could explain the difference of IEN between LM and
      CM stimuli detection when using binary noise as a carrier but not when using a
      plaid or a checkerboard. We conclude that a suboptimal rectification process
      causes higher IEN for CM stimuli detection compared with LM stimuli detection and
      that the intrinsic noise of the binary carrier had a greater impact on the IEN
      than the suboptimal rectification.

PMID- 16889473
TI  - Classification images for detection, contrast discrimination, and identification
      tasks with a common ideal observer.
AB  - We consider three simple forced-choice visual tasks--detection, contrast
      discrimination, and identification--in Gaussian white noise. The three tasks are
      designed so that the difference signal in all three cases is the same difference
      of-Gaussians (DOG) profile. The distribution of the image noise implies that the
      ideal observer uses the same DOG filter to perform all three tasks. But do human
      observers also use the same visual strategy to perform these tasks? We use
      classification image analysis to evaluate the visual strategies of human
      observers. We find significantly different subject classification images across
      the three tasks. The domain of greatest variability appears to be low spatial
      frequencies [<5 cycles per degree (cpd)]. In this range, we find frequency
      enhancement in the detection task, and frequency suppression and reversal in the
      contrast discrimination task. In the identification task, subject classification
      images agree reasonably well with the ideal observer filter. We evaluate the
      effect of nonlinear transducers and intrinsic spatial uncertainty to explain
      divergence from the ideal observer found in detection and contrast discrimination
      tasks.

PMID- 16889474
TI  - The spatiotemporal properties of visual completion measured by response
      classification.
AB  - A constant problem faced by the visual system is the identification of partly
      occluded objects within the visual scene. Recent experiments have demonstrated
      that the visual system engages in a process of visual completion, where the
      hidden parts of objects are filled into the visual representation. Recent
      experiments have also suggested that there may be a time course to this
      completion process. Here, we examined the spatiotemporal properties of visual
      completion by having observers classify figures defined by either luminance
      defined or illusory contours and then correlating their decisions with externally
      added spatiotemporal visual noise. This "response classification" technique
      allowed us to derive a spatiotemporal correlation map (a "classification movie")
      that revealed the locations used by observers at each point in space and time
      during the stimulus presentation. We found that observers gradually became more
      influenced by noise at locations corresponding to illusory contours across the
      first 175 ms of stimulus presentation. Our results are consistent with the idea
      that there is a time course to the completion process on the order of
      approximately 175 ms.

PMID- 16889475
TI  - Additive effects in a rod-and-frame illusion estimated by response
      classification.
AB  - Previous research has shown that not all segments of a square frame are necessary
      to produce the illusory tilt of an enclosed vertical line. Indeed, the presence
      of a single tilted line is often sufficient to induce the illusory tilt of a
      nearby vertical line (Carpenter & Blakemore, 1973). How do the four segments of a
      quadrilateral frame contribute to the illusory tilt if any one of them is
      sufficient to induce the illusion? Response classification (RC) was used in two
      experiments to examine the independent contributions of the four segments of a
      quadrilateral frame to judgments of the direction of tilt of an enclosed vertical
      line. Orientation perturbations were added independently to the four frame
      segments. The orientation of the top segment contributed most systematically to
      these judgments, whereas the orientation of the bottom segment contributed very
      little. Individual differences were observed with two of the four observers
      showing the largest apparent tilt of the test line for shear configurations of
      the quadrilateral in which the top and bottom segments were rotated in a
      direction opposite to the right and left segments. Logistic regression was used
      with a double-pass technique to estimate the relative importance of the four
      segments. Interactions between the segments were not systematically related to
      the observers' judgments. The results are discussed in terms of the utility of RC
      and logistic regression for studying perceptual phenomena whose mechanisms are
      thought to lie at levels such as orientation that are different from those
      typically examined with RC and pixel noise.

PMID- 16889476
TI  - Visual search in noise: revealing the influence of structural cues by gaze
      contingent classification image analysis.
AB  - Visual search experiments have usually involved the detection of a salient target
      in the presence of distracters against a blank background. In such high signal-to
      noise scenarios, observers have been shown to use visual cues such as color,
      size, and shape of the target to program their saccades during visual search. The
      degree to which these features affect search performance is usually measured
      using reaction times and detection accuracy. We asked whether human observers are
      able to use target features to succeed in visual search tasks in stimuli with
      very low signal-to-noise ratios. Using the classification image analysis
      technique, we investigated whether observers used structural cues to direct their
      fixations as they searched for simple geometric targets embedded at very low
      signal-to-noise ratios in noise stimuli that had the spectral characteristics of
      natural images. By analyzing properties of the noise stimulus at observers'
      fixations, we were able to reveal idiosyncratic, target-dependent features used
      by observers in our visual search task. We demonstrate that even in very noisy
      displays, observers do not search randomly, but in many cases they deploy their
      fixations to regions in the stimulus that resemble some aspect of the target in
      their local image features.

PMID- 16889478
TI  - Dimensionality reduction in neural models: an information-theoretic
      generalization of spike-triggered average and covariance analysis.
AB  - We describe an information-theoretic framework for fitting neural spike responses
      with a Linear-Nonlinear-Poisson cascade model. This framework unifies the spike
      triggered average (STA) and spike-triggered covariance (STC) approaches to neural
      characterization and recovers a set of linear filters that maximize mean and
      variance-dependent information between stimuli and spike responses. The resulting
      approach has several useful properties, namely, (1) it recovers a set of linear
      filters sorted according to their informativeness about the neural response; (2)
      it is both computationally efficient and robust, allowing recovery of multiple
      linear filters from a data set of relatively modest size; (3) it provides an
      explicit "default" model of the nonlinear stage mapping the filter responses to
      spike rate, in the form of a ratio of Gaussians; (4) it is equivalent to maximum
      likelihood estimation of this default model but also converges to the correct
      filter estimates whenever the conditions for the consistency of STA or STC
      analysis are met; and (5) it can be augmented with additional constraints on the
      filters, such as space-time separability. We demonstrate the effectiveness of the
      method by applying it to simulated responses of a Hodgkin-Huxley neuron and the
      recorded extracellular responses of macaque retinal ganglion cells and V1 cells.

PMID- 16889477
TI  - Classification images with uncertainty.
AB  - Classification image and other similar noise-driven linear methods have found
      increasingly wider applications in revealing psychophysical receptive field
      structures or perceptual templates. These techniques are relatively easy to
      deploy, and the results are simple to interpret. However, being a linear
      technique, the utility of the classification-image method is believed to be
      limited. Uncertainty about the target stimuli on the part of an observer will
      result in a classification image that is the superposition of all possible
      templates for all the possible signals. In the context of a well-established
      uncertainty model, which pools the outputs of a large set of linear frontends
      with a max operator, we show analytically, in simulations, and with human
      experiments that the effect of intrinsic uncertainty can be limited or even
      eliminated by presenting a signal at a relatively high contrast in a
      classification-image experiment. We further argue that the subimages from
      different stimulus-response categories should not be combined, as is
      conventionally done. We show that when the signal contrast is high, the subimages
      from the error trials contain a clear high-contrast image that is negatively
      correlated with the perceptual template associated with the presented signal,
      relatively unaffected by uncertainty. The subimages also contain a "haze" that is
      of a much lower contrast and is positively correlated with the superposition of
      all the templates associated with the erroneous response. In the case of spatial
      uncertainty, we show that the spatial extent of the uncertainty can be estimated
      from the classification subimages. We link intrinsic uncertainty to invariance
      and suggest that this signal-clamped classification-image method will find
      general applications in uncovering the underlying representations of high-level
      neural and psychophysical mechanisms.

PMID- 16889479
TI  - Strategies optimize the detection of motion transients.
AB  - Strategies are implicitly formed when a task is consistent and can be used to
      improve performance. To investigate how strategies can alter perceptual
      performance, I trained animals in a reaction time (RT) detection task in which
      the probability of a fixed duration motion pulse appearing varied over time in a
      consistent manner. Consistent with previous studies suggesting the implicit
      representation of task timing, I found that RTs were inversely related to the
      probability of the pulse appearing and decreased with training. I then inferred
      the sensory integration underlying responses using behavioral reverse correlation
      analysis. This analysis revealed that training and anticipation optimized
      detection by improving the correlation between sensory integration and the
      spatiotemporal extent of the motion pulse. Moreover, I found that these
      improvements in sensory integration could largely explain observed changes in the
      distribution of RT with training and anticipation. These results suggest that
      training can increase detection performance by optimizing sensory integration
      according to implicitly formed representations of the likelihood and nature of
      the stimulus.

PMID- 16889480
TI  - Estimating nonlinear receptive fields from natural images.
AB  - The response of visual cells is a nonlinear function of their stimuli. In
      addition, an increasing amount of evidence shows that visual cells are optimized
      to process natural images. Hence, finding good nonlinear models to characterize
      visual cells using natural stimuli is important. The Volterra model is an
      appealing nonlinear model for visual cells. However, their large number of
      parameters and the limited size of physiological recordings have hindered its
      application. Recently, a substantiated hypothesis stating that the responses of
      each visual cell could depend on an especially low-dimensional subspace of the
      image space has been proposed. We use this low-dimensional subspace in the
      Volterra relevant-space technique to allow the estimation of high-order Volterra
      models. Most laboratories characterize the response of visual cells as a
      nonlinear function on the low-dimensional subspace. They estimate this nonlinear
      function using histograms and by fitting parametric functions to them. Here, we
      compare the Volterra model with these histogram-based techniques. We use
      simulated data from cortical simple cells as well as simulated and physiological
      data from cortical complex cells. Volterra models yield equal or superior
      predictive power in all conditions studied. Several methods have been proposed to
      estimate the low-dimensional subspace. In this article, we test projection
      pursuit regression (PPR), a nonlinear regression algorithm. We compare PPR with
      two popular models used in vision: spike-triggered average (STA) and spike
      triggered covariance (STC). We observe that PPR has advantages over these
      alternative algorithms. Hence, we conclude that PPR is a viable algorithm to
      recover the relevant subspace from natural images and that the Volterra model,
      estimated through the Volterra relevant-space technique, is a compelling
      alternative to histogram-based techniques.

PMID- 16889481
TI  - Computing dynamic classification images from correlation maps.
AB  - We used Pearson's correlation to compute dynamic classification images of
      biological motion in a point-light display. Observers discriminated whether a
      human figure that was embedded in dynamic white Gaussian noise was walking
      forward or backward. Their responses were correlated with the Gaussian noise
      fields frame by frame, across trials. The resultant correlation map gave rise to
      a sequence of dynamic classification images that were clearer than either the
      standard method of A. J. Ahumada and J. Lovell (1971) or the optimal weighting
      method of R. F. Murray, P. J. Bennett, and A. B. Sekuler (2002). Further, the
      correlation coefficients of all the point lights were similar to each other when
      overlapping pixels between forward and backward walkers were excluded. This
      pattern is consistent with the hypothesis that the point-light walker is
      represented in a global manner, as opposed to a fixed subset of point lights
      being more important than others. We conjecture that the superior performance of
      the correlation map may reflect inherent nonlinearities in processing biological
      motion, which are incompatible with the assumptions underlying the previous
      methods.

PMID- 16889482
TI  - Spike-triggered neural characterization.
AB  - Response properties of sensory neurons are commonly described using receptive
      fields. This description may be formalized in a model that operates with a small
      set of linear filters whose outputs are nonlinearly combined to determine the
      instantaneous firing rate. Spike-triggered average and covariance analyses can be
      used to estimate the filters and nonlinear combination rule from extracellular
      experimental data. We describe this methodology, demonstrating it with simulated
      model neuron examples that emphasize practical issues that arise in experimental
      situations.

PMID- 16889483
TI  - Bayesian models of binocular 3-D motion perception.
AB  - Psychophysical studies on three-dimensional (3-D) motion perception have shown
      that perceived trajectory angles of a small target traveling in depth are
      systematically biased. Here, predictions from Bayesian models, which extend
      existing models of motion-first and stereo-first processing, are investigated.
      These statistical models are based on stochastic representations of monocular
      velocity and binocular disparity input in a binocular viewing geometry. The
      assumption of noise in these inputs together with a plausible prior for 3-D
      motion leads to testable predictions of perceived trajectory angle and velocity.
      Results from two experiments are reported, suggesting that disparity rather than
      motion processing introduces perceptual bias.

PMID- 16889484
TI  - Visual search near threshold: Some features are more equal than others.
AB  - While searching for objects, we combine information from multiple visual
      modalities. Classical theories of visual search assume that features are
      processed independently prior to an integration stage. Based on this, one would
      predict that features that are equally discriminable in single feature search
      should remain so in conjunction search. We test this hypothesis by examining
      whether search accuracy in feature search predicts accuracy in conjunction
      search. Subjects searched for objects combining color and orientation or size;
      eye movements were recorded. Prior to the main experiment, we matched feature
      discriminability, making sure that in feature search, 70% of saccades were likely
      to go to the correct target stimulus. In contrast to this symmetric single
      feature discrimination performance, the conjunction search task showed an
      asymmetry in feature discrimination performance: In conjunction search, a similar
      percentage of saccades went to the correct color as in feature search but much
      less often to correct orientation or size. Therefore, accuracy in feature search
      is a good predictor of accuracy in conjunction search for color but not for size
      and orientation. We propose two explanations for the presence of such asymmetries
      in conjunction search: the use of conjunctively tuned channels and differential
      crowding effects for different features.

PMID- 16889486
TI  - CpG island methylation of tumor-related promoters occurs preferentially in
      undifferentiated carcinoma.
AB  - OBJECTIVE: To understand the role of epigenetic inactivation of tumor-related
      genes in the pathogenesis of thyroid cancer, we investigated the methylation
      profile of distinct thyroid neoplasms. DESIGN: We analyzed the methylation
      pattern of 17 gene promoters in nine thyroid cancer cell lines and in 38 primary
      thyroid carcinomas (13 papillary thyroid carcinoma [PTC], 10 follicular thyroid
      carcinoma [FTC], 9 undifferentiated thyroid carcinoma [UTC], 6 medullary thyroid
      carcinoma [MTC]), 12 goiters, and 10 follicular adenomas (FA) by methylation-
      specific polymerase chain reaction (PCR). Epigenetic inactivation was validated
      by expression analysis. MAIN OUTCOME: Twelve of these genes (RASSF1A, p16(INK4A),
      TSHR, MGMT, DAPK, ERalpha, ERbeta, RARbeta, PTEN, CD26, SLC5A8, and UCHL1) were
      frequently methylated in UTC (15%-86%) and thyroid cancer cell lines (25%-100%).
      In the more aggressive UTC, the mean methylation index (MI = 0.44) was the
      highest compared to other thyroid alterations PTC (MI = 0.29, p = 0.123), FTC (MI
      = 0.15, p = 0.005), MTC (MI = 0.13; p = 0.017), FA (MI = 0.27; p = 0.075) and
      goiters (MI = 0.23; p = 0.024). Methylation of TSHR, MGMT, UCHL1, and p16
      occurred preferentially in UTC and this inactivation was reverted by a
      demethylating agent. CONCLUSIONS: Our results show that hypermethylation of
      several tumor-related gene promoters is a frequent event in UTC. The
      hypermethylation status may be reversed by DNA demethylating agents. Their
      clinical value remains to be investigated.

PMID- 16889485
TI  - Functional characterization of the 258 A/G (D2-ORFa-Gly3Asp) human type-2
      deiodinase polymorphism: a naturally occurring variant increases the enzymatic
      activity by removing a putative repressor site in the 5' UTR of the gene.
AB  - OBJECTIVE: 5' deiodination of thyroid hormone represents an important step in the
      modulation of the hormonal message. Previous studies indicate that the naturally
      occurring polymorphism located in 5'-untranslated region of the gene, 258 A/G, is
      associated with a decrease in circulating T4/T3 ratio, suggesting an increased
      gene expression. The aim of this study was to characterize the gene variant in
      vitro. DESIGN: This was designed as an in vitro study. MAIN OUTCOME: The wild
      type and mutant promoters were cloned into a reporter vector and transfected into
      HEK-293, GH3, and H3B cells. Compared to the 258G wild-type allele, the 258A
      variant had an increased basal activity in all the cell lines (HEK-293 258A 13998
      +/- 371.9 RLU vs. 258G 5593 +/- 124.2 RLU, p < 0.0001). Electrophoresis mobility
      shift assay (EMSA) experiments were performed with nuclear extracts obtained from
      HEK-293 cells and from human thyroid, muscle, and liver. The EMSA experiments
      showed that the 258A variant decreased the binding ability of a nuclear protein
      in HEK-293 cells, thyroid, and muscle. No specific binding was observed in liver
      nuclei. CONCLUSION: These data suggest that the increase in gene transcription
      induced by the 258A polymorphism could be mediated by reduction in the binding
      ability of a putative nuclear repressor.

PMID- 16889487
TI  - Fractional allelic loss of tumor suppressor genes identifies malignancy and
      predicts clinical outcome in follicular thyroid tumors.
AB  - Thyroid follicular tumors can be challenging diagnostically and clinically,
      because the cytologic and histologic features can be subtle and prognosis is also
      difficult to predict. In this study, we analyzed thyroid follicular tumors with
      known long-term follow-up for a molecular panel of tumor suppressor genes to
      determine whether this molecular approach has prognostic significance.
      Microdissection and DNA extraction were performed from tumor and normal tissue.
      Polymerase chain reaction (PCR) was performed for 13 short tandem repeats at or
      near tumor suppressor genes. PCR product was detected using semiquantitative
      capillary gel electrophoresis and fractional allelic loss (FAL) was calculated.
      We included eight adenomas, three minimally invasive carcinomas, four
      angioinvasive carcinomas, and three widely invasive carcinomas with a mean follow
      up of 77 months. Three patients died of disease and an additional two are alive
      with disease recurrence/metastasis. The mean FAL for benign tumors (14%) was
      significantly different from that of malignant tumors (56%, p < 0.001). Patients
      with a follicular tumor who had no evidence of disease recurrence had a mean FAL
      of 22% and those with disease recurrence or death from disease had a mean of 78%
      (p < 0.002). Based on these results, a tumor suppressor gene panel for allelic
      imbalance in follicular-derived tumors (FTT) may correlate with both malignancy
      and outcome in patients with follicular-derived carcinomas of the thyroid.

PMID- 16889489
TI  - Are possible risk factors for differentiated thyroid cancer of prognostic
      importance?
AB  - OBJECTIVE: The only established risk factor for differentiated thyroid cancer
      (DTC) is ionizing radiation. How ionizing radiation and other possible risk
      factors for DTC influence the prognosis has not extensively been investigated. We
      studied if factors such as smoking, number of children, previous thyroid
      disorders, previous radiotherapy toward the neck, family history of thyroid
      diseases, and malignancies influenced survival for patients with DTC. DESIGN: A
      nested case-control study was conducted within the cohort of all patients
      diagnosed with DTC in Sweden between 1958-1987. Cases consisted of patients who
      died from DTC. One control, matched by age at diagnosis, gender, and calendar
      period was randomly selected from the risk set for each case. Information of risk
      factors was collected from the medical records. Associations between these
      factors and prognosis were assessed using conditional logistic regression. MAIN
      OUTCOME: Smokers had a borderline significant increased risk of dying from DTC.
      Previous radiotherapy towards the neck region had no prognostic implication. A
      family history of DTC influenced prognosis although not significant due to few
      cases. The remaining risk factors studied did not influence survival.
      CONCLUSIONS: In conclusion, smokers seemed to have a worsened prognosis compared
      to nonsmokers and a family history of thyroid cancer had a nonsignificant
      negative effect on survival.

PMID- 16889488
TI  - Differential Susceptibility of BALB/c and BALB/cBy mice to Graves'
      hyperthyroidism.
AB  - BALB/c mice are susceptible to the induction of Graves' hyperthyroidism. To
      investigate the susceptibility of BALB/c substrains of mice to the induction of
      hyperthyroidism, we immunized BALB/cJ and BALB/cByJ mice with an adenovirus
      expressing amino acid residues 1-289 of thyrotropin receptor (TSHR). The data
      presented in this article showed that 17 of 26 (65%) BALB/c and only 4 of 30
      (13%) BALB/cBy mice developed hyperthyroidism. Hyperthyroid mice displayed
      characteristics of Graves' disease, such as thyroid-stimulating antibodies and
      enlarged thyroid glands. To explore the differences in the susceptibility of
      these substrains for hyperthyroidism, we examined the TSHR antibodies in three
      different assays. The TSHR antibodies determined in a radioreceptor assay (TSH
      binding inhibitory immunoglobulins) were similar in both of these BALB/c
      substrains. The TSHR antibody titers of total IgG, IgG1, and IgG2a were measured
      by an enzyme-linked immunosorbent assay and were found to be similar in these
      mice. There were no significant differences between these two groups of mice in
      the thyroid-stimulating antibody activity. However, BALB/cBy mice had
      significantly higher TSH-blocking antibody activity compared to BALB/c mice. TSHR
      specific proliferation of splenocytes and secretion of cytokines interferon-gamma
      and interleukin-4 by spleen cells were comparable in both the groups. BALB/cJ and
      BALB/cByJ mice both belong to same MHC haplotype, H-2(d), but differ in the Qa-2
      region of class Ib molecule. This report shows the importance of other genes,
      such as Qa-2 region of class Ib molecule in addition to MHC class II, in the
      susceptibility of Graves' hyperthyroidism.

PMID- 16889490
TI  - Testicular function after radioiodine therapy in patients with thyroid cancer.
AB  - Our aim was to assess testicular function in patients treated with high-dose
      radioiodine. Luteinizing hormone (LH), follicle-stimulating hormone (FSH), and
      testosterone levels were determined in 52 men with thyroid carcinoma before and
      6, 12, and 18 months after radioiodine therapy (3.7-5.5 GBq (131)I; mean, 4.25
      GBq (131)I) (group 1) and were also determined before and 18 months after the
      last radioiodine therapy in 22 patients who received high cumulative activities
      (13-27.7 GBq; mean, 20.3 GBq (131)I) (group 2). FSH levels were increased 6
      months after therapy in all patients of group 1, while a decline was observed
      after 12 months, with 37 of 52 (71%) subjects presenting normal values. FSH
      values returned to normal after 18 months in all patients. In group 2, 12 of 22
      (54.5%) patients presented elevated FSH and 8 (66%) of these individuals had
      oligospermia. Six months after radioiodine, increased LH levels were observed in
      only 5 of 52 (9.6%) patients of group 1, which returned to normal after 12
      months, and in 5 of 22 (22%) of group 2. All patients showed normal testosterone
      levels. We conclude that 131I therapy may cause impairment of testicular
      function. A generally transient increase in FSH is highly common but is usually
      reversed within 18 months. Oligospermia was common (one third) after high
      cumulative (131)I activities. Becausee we did not perform a spermiogram before
      therapy, we cannot state that high cumulative (131)I activities cause permanent
      infertility. We recommend the routine use of sperm banks in the cases of men who
      still wish to have children and who will undergo therapy with (131)I activities
      of 14 GBq or more or in the case of patients with pelvic metastases.

PMID- 16889491
TI  - Trisomy 21 causes persistent congenital hypothyroidism presumably of thyroidal
      origin.
AB  - OBJECTIVE AND DESIGN: Lowered neonatal plasma thyroxine (T(4)) and mildly
      elevated thyrotropin concentrations together with developmental benefits from
      neonatally started T(4) treatment in a randomized clinical trial demonstrated
      Down syndrome (DS) neonates to be mildly hypothyroid, at least during their first
      weeks of life. To prove that this hypothyroid state persists beyond this period
      in all, and to elucidate its etiology, we evaluated the course of the thyroid
      function determinants in all DS infants participating in this 24-month trial.
      MAIN OUTCOME: Mean plasma thyrotropin concentrations and thyrotropin frequency
      distributions of 97 placebo-treated infants were persistently shifted to
      substantially higher concentrations, while free T(4) frequency distributions were
      in the lower two thirds of the reference interval. Mean thyroglobulin
      concentrations were normal. To normalize plasma thyrotropin, T(4)-treated DS
      infants (N = 99) needed rather high free T(4) concentrations, like T(4)- treated
      non-DS children with thyroidal congenital hypothyroidism. At ages 12 and 24
      months, thyroid peroxidase antibodies were detected in 1.1% and 5.4% of all DS
      infants. CONCLUSIONS: These findings suggest that as a group DS infants have a
      novel type of persistent mild congenital hypothyroidism, presumably of thyroidal
      origin. The group character suggests a direct relation with the trisomic state of
      chromosome 21, hypothetically through genomic dosage imbalance of dosage
      sensitive genes interfering with thyroid hormone production.

PMID- 16889492
TI  - Thyroid function and serum ferritin levels: the study of health in Pomerania.
AB  - OBJECTIVE: Serum ferritin levels are assumed to be an atherosclerotic risk
      factor. Ferritin production is increased in individuals with activated liver
      production, which has been shown in hyperthyroid conditions. An association
      between subclinical hyperthyroidism and serum ferritin levels would add an
      explanation to the relation between low serum thyrotropin levels and mortality.
      The aim of the present analysis was to investigate an association between thyroid
      function and serum ferritin levels. We hypothesized low serum thyrotropin to be
      related to high serum ferritin levels. DESIGN: The Study of Health in Pomerania
      (SHIP) is a population-based study comprising male and female adults aged 20 to
      79 years. Data of 4111 subjects (2071 females) were available for the present
      analysis. Serum ferritin levels were determined by an immunoturbidimetric assay.
      Multivariable analyses were performed to investigate an independent relation
      between thyroid function and serum ferritin levels. MAIN OUTCOME: Age-adjusted
      and gender-stratified analyses revealed no association between thyroid function
      and serum ferritin levels, neither in females nor in males. This finding remained
      stable after adjustment for potential confounders and in sensitivity analyses.
      CONCLUSION: There was no association between thyroid function and serum ferritin
      levels. We conclude that serum ferritin levels do not account for the relation
      between subclinical hyperthyroidism and vascular mortality.

PMID- 16889493
TI  - Triiodothyronine production in Graves' hyperthyroidism.
AB  - OBJECTIVE: To quantify the relative contributions of thyroid secretion and
      peripheral generation to triiodothyronine (T(3)) production in untreated Graves'
      hyperthyroidism. PATIENTS, DESIGN, AND MEASUREMENTS: Thirty-one patients with
      hyperthyroidism, of whom 6 had T(3) toxicosis, and 21 surgically and radioiodine
      ablated patients with thyroid cancer on thyroid stimulating hormone-suppressive
      therapy in whom serum T(3) should reflect peripheral generation alone were
      compared with respect to serum free thyroxine (T(4)) and serum free T(3)
      concentrations. MAIN OUTCOMES: Serum free T(4)/free T(3) molar ratios were
      virtually identical in the patients with T(4)+T(3) toxicosis (2.7 +/- 0.4) and
      those with T(3) toxicosis (2.6 +/- 0.4) and were significantly lower than in the
      patients with thyroid cancer (4.0 +/- 0.4) (p < 0.001). In the hyperthyroid
      patients, peripherally generated T(3) was calculated as the quotient of the
      individual serum free T(4) concentration and the free T(4)/free T(3) molar ratio
      in thyroid cancer; this value was subtracted from the individual measured free
      T(3) concentration to derive the value for secreted T3. Secreted T(3) accounted
      for 33 +/- 6% of T(3) production in T(4)+T(3) toxicosis and 34 +/- 10% in T(3)
      toxicosis. CONCLUSIONS: This study indicates that about one third of T3
      production in untreated Graves' hyperthyroidism, irrespective of whether
      presenting as T4+T3 toxicosis or T3 toxicosis, arises from thyroid secretion as
      compared to about 20% in normal individuals.

PMID- 16889494
TI  - Intravenous methimazole in the treatment of refractory hyperthyroidism.
AB  - BACKGROUND: Management of a hyperthyroid patient unable to take oral or rectal
      medication is a difficult clinical problem. The need for an alternative
      parenteral route of antithyroid medication administration in thyrotoxic patients
      occurs in certain rare cases, such as emergent gastrointestinal surgery, bowel
      ileus or obstruction, or severe vomiting and diarrhea. We report a simple and
      successful protocol for the preparation and use of intravenous methimazole (MMI)
      for treatment of hyperthyroidism in patients intolerant of orally and rectally
      administered thionamides. METHODS: Five hundred milligrams of methimazole USP
      powder was reconstituted with pH-neutral 0.9% sodium chloride solution to a final
      volume of 50 mL using aseptic technique, then filtered through a 0.22-microm
      filter. MMI injection was administered as a slow intravenous push over 2 minutes
      and followed by a saline flush. CASES: A 76-year-old man, intolerant of oral and
      rectal medications because of an ileus and intractable diarrhea, who developed
      worsening thyrotoxicosis after an emergent spinal cord decompression, and a 42
      year-old man with chronic liver disease and hyperthyroidism, requiring emergent
      exploratory laparotomy and maintenance of complete bowel rest because of
      persistent gastrointestinal bleeding were rendered euthyroid using intravenous
      MMI. CONCLUSION: Two cases of hyperthyroidism successfully treated with a
      preparation of intravenous MMI are described.

PMID- 16889495
TI  - Transient vocal cord paralysis after fine-needle aspiration biopsy of thyroid
      tumor.
AB  - OBJECTIVE: Complications of thyroid fine-needle aspiration biopsy (FNAB) are
      exceedingly rare. Hematoma formation is the most commonly encountered
      complication. Infection and seeding of carcinoma cells in the needle track has
      also been reported in a rare case. Here we describe patients diagnosed as having
      transient vocal cord paralysis after FNAB of benign thyroid tumor. DESIGN:
      Retrospective review of patients with concurrent diagnosis of vocal cord
      paralysis after FNAB. MAIN OUTCOME: Among 10,974 patients who underwent FNAB, 4
      patients showed vocal cord paralysis on laryngoscopy. These patients had solid
      and/or cystic lesion in the thyroid. Routine FNAB of the nodule was performed
      using a 23-gauge needle. Cytologic findings were benign tumor. Change of voice in
      the patients occurred 1 or 2 days after FNAB and vocal cord paralysis ipsilateral
      to FNAB was determined by flexible laryngoscopy. Vocal cord paralysis of all
      patients resolved spontaneously within 6 months (average, 4 months). CONCLUSION:
      Although the incidence of vocal cord paralysis in patients with thyroid tumor
      after FNAB is reported to be 0.036%, the true incidence is unknown because
      asymptomatic subjects are not screened. This report should alert the examiner to
      the possibility of vocal cord palsy after FNAB.

PMID- 16889496
TI  - Ectopic thyroid tissue and Graves' disease in an elderly patient.

PMID- 16889497
TI  - Graves' disease discovered by angiography.

PMID- 16889498
TI  - Thyroid uptake of radioactive iodine and scintigraphy in mice.

PMID- 16889499
TI  - Factors predicting the occurrence of hypothyroidism after hemithyroidectomy.

PMID- 16889500
TI  - Thyroid stimulation-blocking antibody and Graves' ophthalmopathy.

PMID- 16889501
TI  - Treatment-resistant severe, active Graves' ophthalmopathy successfully treated
      with B lymphocyte depletion.

PMID- 16889503
TI  - Engineering of vascularized transplantable bone tissues: induction of axial
      vascularization in an osteoconductive matrix using an arteriovenous loop.
AB  - INTRODUCTION: Vascularization remains an obstacle to engineering of larger volume
      bone tissues. Our aim was to induce axial vascularization in a processed bovine
      cancellous bone (PBCB) matrix using an arteriovenous (AV) loop (artery, vein
      graft, and vein). METHODS: Custom-made PBCB discs (9 x 5 mm) were implanted into
      rats. In group A (n = 19), the matrices were inserted into microsurgically
      constructed AV loops between the femoral vessels using a vein graft from the
      contralateral side. In group B (n = 19), there was no vascular carrier. The
      matrices were encased in isolation chambers. After 2, 4, and 8 weeks, the animals
      were perfused with India ink via the abdominal aorta. Matrices were explanted and
      subjected to histological and morphometric analysis. Results were compared with
      intravital dynamic micro & magnetic resonance imaging and scanning electron
      microscopy images of vascular corrosion replicas. RESULTS: In group A,
      significant vascularization of the matrix had occurred by the 8th week. At this
      time, vascular remodeling with organization into vessels of different sizes was
      evident. Blood vessels originated from all 3 zones of the AV loop. Group A was
      significantly superior to group B in terms of vascular density and
      vascularization kinetics. DISCUSSION: This study demonstrates for the first time
      successful vascularization of solid porous matrices by means of an AV loop.
      Injection of osteogenic cells into axially prevascularized matrices may
      eventually create functional bioartificial bone tissues for reconstruction of
      large defects.

PMID- 16889504
TI  - Microencapsulated cells genetically modified to overexpress human transforming
      growth factor-beta1: viability and functionality in allogeneic and xenogeneic
      implant models.
AB  - This study explores the suitability of using encapsulated genetically modified
      fibroblasts for orthopedic tissue engineering by examining cell survival and
      persistence of human transforming growth factor-beta (hTGF-beta) overexpression
      in xenogeneic and allogeneic implant models. Human wild-type fibroblasts,
      modified to produce a latent form of hTGF-beta, and murine mutant-type
      fibroblasts, engineered to release a constitutively active form of hTGF-beta,
      were encapsulated separately in Ca2+ -alginate microcapsules. Following a
      percentage viability assessment by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5
      diphenyltetrazolium bromide) test, microcapsules were implanted into either the
      subcutaneous or intraperitoneal cavities of mice. Explanted encapsulated cells
      were characterized for percentage viability and subjected to a release study and
      a viability test 1 week and 3 weeks following implantation, a time frame
      consistent with the requirement for orthopedic tissue engineering application of
      this growth factor. On average, percentage viabilities of encapsulated cells were
      64%at implantation, 52% at explantation, and 56%after 1 week following either 1-
      or 3-week explantation. hTGF-beta release declined following in vivo
      implantation, more so for xenogeneic than allogeneic models, but remained in the
      clinically attractive range of 2 to 30 ng/(10(6) implanted cells 24 h). This
      technical platform for hTGF-beta is very encouraging for cartilage regeneration
      using orthopedic tissue engineering, and further evaluation is warranted.

PMID- 16889505
TI  - Lentiviral manipulation of gene expression in human adult and embryonic stem
      cells.
AB  - Human stem cells could revolutionize the field of medicine by providing a diverse
      range of cell types for tissue replacement therapies and drug discovery. To
      achieve this goal, genetic tools need to be optimized and developed for
      controlling and manipulating stem cells ex vivo. Here we describe a lentiviral
      delivery system capable of high infection rates in human mesenchymal and
      embryonic stem cells. The lentiviral backbone was modified to express mono- and
      bi-cistronic transgenes and was also used to deliver short hairpin ribonucleic
      acid for specific silencing of gene expression in human stem cells. We show that
      lentiviral transduction can be used to alter gene expression without altering the
      genes' ability to differentiate in vitro. These vectors will enable rapid
      analysis of gene function in stem cells and permit the generation of knock-in /
      knock-out models of human disease in the rapidly developing field of gene
      therapy.

PMID- 16889506
TI  - Efficacy of bone marrow-derived stem cells in strengthening osteoporotic bone in
      a rabbit model.
AB  - Osteoporosis might be due to defects in mesenchymal stem cells (MSCs) that lead
      to reduced proliferation and osteoblast differentiation. We hypothesized that
      transplantation of MSCs into sites at risk for developing osteoporotic bone could
      improve bone structure and biomechanics. The aim of this study was to establish
      an osteoporosis rabbit model by ovariectomy (OVX), characterize the autologous
      MSCs from the OVX rabbits, and transplant the autologous MSCs into the OVX
      rabbits. MSCs harvested from bone marrow of normal and OVX rabbits were culture
      expanded and differentiated in osteogenic medium. Phenotypes were evaluated by
      collagen I immunostaining, von Kossa staining, and quantitative assays of bone
      specific alkaline phosphatase (B-ALP) and osteocalcin (OCN). MSCs were
      transfected with green fluorescence protein (GFP) and implanted in the gluteus
      muscle to trace their fate in vivo. Cultured autologous MSCs from OVX rabbits
      were constructed in calcium alginate gels and then transplanted in the distal
      femurs. At 4 and 8 weeks after implantation, histomorphometrical and
      biomechanical analyses were performed on the samples. MSCs from OVX rabbits
      displayed higher B-ALP activity, but had similar OCN levels as compared to those
      from sham rabbits. After 8 weeks of implantation, more bone apposition was found
      in the MSC-alginate-treated group. Histomorphometry indicated increased
      trabecular thickness. Histology also illustrated improved microstructures with
      newly formed osteoids and enhanced trabecular thickness. In addition,
      biomechanical testing revealed stronger stiffness in the MSC-alginate treatment
      group. Therefore, this study implies that transplantation of MSCs can help to
      strengthen osteoporotic bone in rabbits.

PMID- 16889507
TI  - Aragonite crystalline biomatrices support astrocytic tissue formation in vitro
      and in vivo.
AB  - Astrocytes play a pivotal role in the development and function of the central
      nervous system by regulating synaptic activity and supporting and guiding growing
      axons. It is therefore a central therapeutic and scientific challenge to develop
      means to control astrocytic survival and growth. We cultured primary hippocampal
      astrocytes on a crystalline three-dimensional (3D) aragonite biomatrix prepared
      from the exoskeleton of the coral Porites lutea. Such culturing led to the
      formation of astrocytic tissue-like 3D structures in which the cells had a higher
      survival rate than astrocytes grown in conventional cell culture. Within the pore
      void areas, multiple layers of astrocytic processes formed concave sheet
      structures that had no physical contact with the surface. The astrocytes attached
      to the crystalline perpendicular edges of the crystalline template surface
      extended processes in 3D and expressed glial fibrillary acidic protein. The
      astrocytes also expressed gap junctions and developed partly synchronized
      cytosolic Ca2+ oscillations. Preliminary in vivo models showed that astrocytic
      networks were also developed when the matrices were implanted into cortical areas
      of postnatal rat brains. Hence, we suggest that the biomatrix is a biocompatible
      supportive scaffold for astrocytes and may be exploited in applications for
      neuronal tissue restoration in injured or diseased central nervous system.

PMID- 16889508
TI  - Chondrocyte phenotype in engineered fibrous matrix is regulated by fiber size.
AB  - A biomaterial scaffold acting as a functional substitute for the native
      extracellular matrix provides space for cell accommodation. In this study, we
      seeded chondrocytes, isolated from 4- to 6-month-old calves, in 2 types of poly(L
      lactide) scaffolds, composed of micro- and nanofibers, and compared the effects
      on cellular activities. Scanning electron microscopy revealed a well-spread
      morphology for chondrocytes grown on microfibers. In contrast, chondrocytes on
      the nanofibers were found to have a rounded morphology and displayed a
      disorganized actin cytoskeletal structure compared to the organized cytoskeleton
      seen in well-spread chondrocytes culture on the microfibrous scaffold. Both
      scaffolds supported chondrocyte proliferation, with a higher rate seen in
      cultures in nanofibrous scaffold. Quantitative reverse transcription-polymerase
      chain reaction analysis showed that both cultures supported expression of
      collagen types I and II and aggrecan. Biochemical analysis showed a higher level
      of sulfated glycosaminoglycan in the nanofiber culture, confirmed by more intense
      alcian blue histologic staining. The nanofiber cultures also showed higher
      immunostaining for collagen types II and IX, aggrecan, and cartilage proteoglycan
      link protein. Based on these results, we conclude that chondrocytes respond
      differently to fibrous scaffolds of varying diameters, and that the scaffolds
      made of nanofibrous biomaterial promote efficient cell-based cartilage tissue
      engineering.

PMID- 16889509
TI  - Maturation of tissue engineered cartilage implanted in injured and osteoarthritic
      human knees.
AB  - The regeneration of damaged organs requires that engineered tissues mature when
      implanted at sites of injury or disease. We have used new analytic techniques to
      determine the extent of tissue regeneration after treatment of knee injury
      patients with a novel cartilage tissue engineering therapy and the effect of pre
      existing osteoarthritis on the regeneration process. We treated 23 patients, with
      a mean age of 35.6 years, presenting with knee articular cartilage defects 1.5
      cm2 to 11.25 cm2 (mean, 5.0 cm2) in area. Nine of the patients had X-ray evidence
      of osteoarthritis. Chondrocytes were isolated from healthy cartilage removed at
      arthroscopy. The cells were cultured for 14 days, seeded onto esterified
      hyaluronic acid scaffolds (Hyalograft C), and grown for a further 14 days before
      implantation. A second-look biopsy was taken from each patient after 6 to 30
      months (mean, 16 months). After standard histological analysis, uncut tissue was
      further analyzed using a newly developed biochemical protocol involving digestion
      with trypsin and specific, quantitative assays for type II collagen, type I
      collagen, and proteoglycan, as well as mature and immature collagen crosslinks.
      Cartilage regeneration was observed as early as 11 months after implantation and
      in 10 out of 23 patients. Tissue regeneration was found even when implants were
      placed in joints that had already progressed to osteoarthrosis. Cartilage
      injuries can be effectively repaired using tissue engineering, and osteoarthritis
      does not inhibit the regeneration process.

PMID- 16889511
TI  - New technique of seeding chondrocytes into microporous poly(L-lactide-co-epsilon
      caprolactone) sponge by cyclic compression force-induced suction.
AB  - The initial requirement for a functional engineered cartilage tissue is the
      effective and reproducible seeding of chondrocytes into the interior of
      microporous scaffolds. High seeding efficiency, high cell viability, uniform cell
      distribution, and short operation time are also essential. We devised a new
      technique of seeding rabbit chondrocytes into microporous poly(L-lactide-co
      epsilon-caprolactone) (PLCL) (porosity, 71- 80%; wall thickness, 2 and 6 mm)
      sponges under compression force-induced suction using a custom designed loading
      apparatus. Cell distribution and cell viability were determined using confocal
      laser scanning microscopy with fluorescent dye-staining techniques. Factors that
      affect the quality of a cell seeded construct were studied, namely, the porosity
      and thickness of sponges and suction cycles. Under 1 cycle of suction, an
      increase in porosity promoted cell seeding efficiency (CSE; defined as the
      percentage of the number of cells in the sponges relative to the initial number
      of cells seeded), cell viability (at 1 day post seeding), and a relatively
      uniform cell distribution, whereas thick sponges exhibited an inhomogeneous cell
      distribution irrespective of incubation time. Multiple cycles of suction of 5 and
      10 at 0.1 Hz significantly improved the CSE, whereas high cell viability was
      maintained and even spatial cell distribution was achieved in 1 week. This study
      revealed that our newly developed cell seeding technique with multiple cycles of
      suction is a promising approach to inoculating cells into microporous sponges
      with high CSE, high cell viability, and homogeneous cell distribution.

PMID- 16889510
TI  - A newly developed bioartificial pancreas successfully controls blood glucose in
      totally pancreatectomized diabetic pigs.
AB  - Construction of a safe and functional bioartificial pancreas (BAP) that provides
      an adequate environment for islet cells may be an important approach to treating
      diabetic patients. Various types of BAP devices have been developed, but most of
      them involve extravascular implantation of islets in microcapsules or diffusion
      chambers. These devices have poor diffusive exchange between the islets and
      blood, and often rupture. To overcome these problems, we developed a new type of
      BAP composed of polyethylene-vinyl alcohol (EVAL) hollow fibers that are
      permeable to glucose and insulin and a poly-amino-urethane-coated, non-woven
      polytetrafluoroethylene (PTFE) fabric that allows cell adhesion. Porcine islets
      attached to the surface of the PTFE fabric, but not to the surface of the EVAL
      hollow fibers, allowing nutrient and oxygen exchange between blood flowing inside
      the fibers and cells outside. We inoculated this BAP with porcine islets and
      connected it to the circulation of totally pancreatectomized diabetic pigs. We
      found that blood glucose levels were reduced to a normal range and general health
      was improved, resulting in longer survival times. In addition, regulation of
      insulin secretion from the BAP was properly controlled in response to glucose
      both in vitro and in vivo. These results indicate that our newly developed BAP
      may be a potential therapy for the treatment of diabetes in humans.

PMID- 16889512
TI  - In situ monitoring of tendon structural changes by elastic scattering
      spectroscopy: correlation with changes in collagen fibril diameter and crimp.
AB  - The aim of this study was to monitor structural changes in loaded rabbit digital
      flexor tendons in situ and ex situ via elastic scattering spectroscopy (ESS). The
      optical setup consisted of a xenon white light source (lambda = 320-860 nm),
      connected to a fiber optic probe (with a source-detector separation of
      approximately 350 microm) and a spectrometer, controlled by a personal computer
      (PC). Cadaveric rabbit tendons were studied in situ under 3 tensional regimens:
      unloaded (no extrinsic tension applied), stretched, and 1-kg loaded and compared
      with excised tendons (i.e., no tension). Four times more light was detected in in
      situ unloaded tendons perpendicular to the tendon long axis than parallel to it.
      Backscatter anisotropy was expressed as the anisotropy factor (AF600nm: ratio of
      greatest to least backscatter intensity, measured with orthogonal probe
      positions). Differences in backscatter anisotropy between tendons from different
      digits were not significant. AF600nm had the smallest value (2.72 +/- 0.38) for
      the least aligned tendon preparations (excised tendons), and increased to 7.17 +/
      0.54 (1-kg loaded) as in situ loads were applied. Electron microscopy revealed
      that the distribution of collagen fibril diameters changed as loads were applied,
      with the diameter of larger fibrils decreasing approximately 33% for 1-kg loaded
      compared with excised tendons. Polarized light microscopy showed a characteristic
      crimp pattern in excised tendons, but this was hardly detectable in unloaded
      tendons and not detectable in tendons fixed in situ under a 1-kg load. We propose
      that the increase in optical anisotropy is a function of collagen fibril
      straightening and reducing fibril diameter as the tendon undergoes progressive
      loading. These findings are important for monitoring structure in vivo and in
      bioreactors for tissue engineers.

PMID- 16889513
TI  - Paracrine release of insulin-like growth factor 1 from a bioengineered tissue
      stimulates skeletal muscle growth in vitro.
AB  - Bioengineered tissues transduced to secrete recombinant proteins may serve as a
      long-term delivery vehicle for therapeutic proteins when implanted in vivo.
      Insulin-like growth factor 1 (IGF1) is an anabolic growth factor for skeletal
      muscle that can stimulate myoblast proliferation and myofiber hypertrophy. To
      determine whether the release of IGF1 from an engineered bioartificial skeletal
      muscle (BAM) could stimulate the growth of skeletal muscle in a paracrine manner,
      we established an in vitro perfusion system for genetically engineered IGF1 BAMs.
      BAMs were bioengineered from C2C12 murine myoblasts stably transduced with a
      retroviral vector to synthesize and secrete IGF1 (C2-IGF1 BAMs). C2-IGF1 BAMs or
      nontransduced control C2 BAMs were cocultured with avian BAMS (ABAMs) in
      constantly perfused biochambers. During 11 days of perfusion, IGF1 levels in the
      C2-IGF1 BAM perfusion medium increased linearly from 1 to 20 ng/mL. The ABAMs
      maintained in biochambers with the C2-IGF1 BAMs had significantly more myofibers
      (69%, p < 0.005) and larger myofiber cross-sectional areas (40%, p < 0.001)
      compared to those cocultured with control C2 BAMs. These studies show that levels
      of IGF1 secreted from the C2-IGF1 BAMs are sufficient to produce an anabolic
      paracrine effect on nongenetically engineered BAMs, and the in vitro perfusion
      system provides a model for screening proteins effective in stimulating localized
      skeletal muscle growth.

PMID- 16889514
TI  - Phenotypic drift in human tenocyte culture.
AB  - Tendon ruptures are increasingly common, repair can be difficult, and healing is
      poorly understood. Tissue engineering approaches often require expansion of cell
      numbers to populate a construct, and maintenance of cell phenotype is essential
      for tissue regeneration. Here, we characterize the phenotype of human Achilles
      tenocytes and assess how this is affected by passaging. Tenocytes, isolated from
      tendon samples from 6 patients receiving surgery for rupture of the Achilles
      tendon, were passaged 8 times. Proliferation rates and cell morphology were
      recorded at passages 1, 4, and 8. Total collagen, the ratio of collagen types I
      and III, and decorin were used as indicators of matrix formation, and expression
      of the integrin beta1 subunit as a marker of cell-matrix interactions. With
      increasing passage number, cells became more rounded, were more widely spaced at
      confluence, and confluent cell density declined from 18,700/cm2 to 16,100/cm2 ( p
      = 0.009). No change to total cell layer collagen was observed but the ratio of
      type III to type I collagen increased from 0.60 at passage 1 to 0.89 at passage 8
      ( p < 0.001). Decorin expression significantly decreased with passage number,
      from 22.9 +/- 3.1 ng/ng of DNA at passage 1, to 9.1 +/- 1.8 ng/ng of DNA at
      passage 8 ( p < 0.001). Integrin expression did not change. We conclude that the
      phenotype of tenocytes in culture rapidly drifts with progressive passage.

PMID- 16889516
TI  - Effects of cell seeding density and collagen concentration on contraction
      kinetics of mesenchymal stem cell-seeded collagen constructs.
AB  - Our group has been engineering cell-scaffold constructs to improve tendon repair
      by contracting mesenchymal stem cells (MSCs) in collagen gels and then evaluating
      their repair potential in wound sites in rabbits. Because the construct's initial
      conditions may influence the ultimate repair outcome, this two-part study sought
      to distinguish which factors most influence contraction kinetics in culture.
      (1)We optically determined if varying cell-to-collagen ratio significantly
      affected construct contraction. Temporal changes in construct area were monitored
      up to 168 h for 4 cell-to-collagen ratios (HK = 0.04, LK = 0.08, HM = 0.4, and LM
      = 0.8, where H, L = 2.6, 1.3 mg/mL collagen and K,M = 0.1, 1 million cells/mL,
      respectively).A mathematical model was created with terms that represent the
      different combinations of cell densities and collagen concentrations in order to
      predict the contraction kinetics as a function of time. Highly significant
      differences in construct areas were found among all 4 ratios after 8 h of
      contraction with the exception of the LK (0.08) vs. HM(0.4) conditions. This
      similar pattern raised the question of whether cell density or collagen
      concentration more influenced these events. (2) To isolate these effects, the
      contraction kinetics of the HM construct were compared to those of a new
      construct (L5K) with equivalent cell-to-collagen ratio (0.4) but half the cell
      density (500 K MSCs/mL) and half the collagen concentration (1.3 mg/mL). The L5K
      construct contracted significantly faster and more completely than the HM
      construct but no differently than the LM construct. These results indicate that
      above a threshold value of cell density, percentage reductions in collagen
      concentration influence contraction kinetics more than equivalent percentage
      increases in cell seeding density. The fact that our model successfully predicted
      intermediate time points of contraction suggests its utility for examining other
      cell and collagen densities. Controlling scaffold as well as cellular initial
      conditions will be critical in achieving our goal of functional tissue
      engineering (FTE) a successful tendon repair.

PMID- 16889515
TI  - A rapid seeding technique for the assembly of large cell/scaffold composite
      constructs.
AB  - These studies address critical technical issues involved in creating human
      mesenchymal stem cell (hMSC)/ scaffold implants for cartilage repair. These
      issues include obtaining a high cell density and uniform spatial cell
      distribution within the scaffold, factors that are critical in the initiation and
      homogeneity of chondrogenic differentiation. For any given scaffold, the initial
      seeding influences cell density, retention, and spatial distribution within the
      scaffold, which eventually will affect the function of the construct. Here, we
      discuss the development of a vacuum-aided seeding technique for HYAFF -11 sponges
      which we compared to passive infiltration. Our results show that, under the
      conditions tested, hMSCs were quantitatively and homogeneously loaded into the
      scaffolds with 90+% retention rates after 24 h in perfusion culture with no
      negative effect on cell viability or chondrogenic potential. The retention rates
      of the vacuum-seeded constructs were at least 2 times greater than those of
      passively seeded constructs at 72 h. Histomorphometric analysis revealed that the
      core of the vacuum-seeded constructs contained 240% more cells than the core of
      passively infiltrated scaffolds. The vacuum seeding technique is safe, rapid,
      reproducible, and results in controlled quantitative cell loading, high
      retention, and uniform distribution.

PMID- 16889517
TI  - 3-O-methyl-D-glucose improves desiccation tolerance of keratinocytes.
AB  - Transplantation of autologous skin grafts and tissue engineered skin replacements
      for the treatment of burns, trauma, and ulcerative wounds has been shown to
      restore a protective barrier to infection and fluid loss, reduce heat loss,
      provide mechanical strength, diminish pain, and dampen the hypermetabolic stress
      response to thermal injury. Patencies of these grafts depend mainly on the high
      viability and sustained function of the enmeshed keratinocytes. With growing
      demand in tissue replacement therapies, development of successful and economical
      preservation techniques for skin grafts and replacements becomes essential. In
      this regard, if attained, desiccated state storage offers an economical solution
      to availability, storage, and transportation problems. Recent studies indicate
      that carbohydrates are very efficient in stabilizing mammalian cells against
      various types of stresses, including those associated with cryopreservation and
      desiccation. In this study we introduce the use of 3-O-methyl-D-glucose (3-OMG),
      a nonmetabolizable glucose derivative, as a new means of providing protection for
      keratinocytes undergoing desiccation. We show that with decreasing water
      contents, viability of the cells decreases; however, at the same water content
      the immediate post-rehydration viability and long-term survival of the cells
      exposed to 3-OMG are much higher than those of controls.

PMID- 16889518
TI  - Morphological and functional analysis of rat hepatocyte spheroids generated on
      poly(L-lactic acid) polymer in a pulsatile flow bioreactor.
AB  - Liver neo-tissue suitable for transplantation has not been established. Primary
      rat hepatocytes were cultured on three-dimensional biodegradable polymer matrices
      in a pulsatile flow bioreactor with the intention of inducing tissue formation
      and improving cell survival. Functional and structural analysis of the
      hepatocytes forming liver neo-tissue was performed. Biodegradable poly(L-lactic
      acid) (PLLA) polymer discs were seeded with 4 x 10(6) primary rat hepatocytes
      each, were exposed to a pulsatile medium flow of 24 mL/min for 1, 2, 4, or 6 days
      and were investigated for monoethylglycinexylidine (MEGX) formation, ammonia
      detoxification, Cytokeratin 18 (CK18) expression, and preserved glycogen storage.
      Fine structural details were obtained using scanning and transmission electron
      microscopy. Spheroids of viable hepatocytes were formed. MEGX-specific production
      was maintained and ammonia removal capacity remained high during the entire flow
      culture period of 6 days. CK18 distribution was normal. Periodic-acid- Schiff
      reaction demonstrated homogenous glycogen storage. The hepatocytes reassembled to
      form intercellular junctions and bile canaliculi. Functional and morphological
      analysis of rat hepatocytes forming spheroids in a pulsatile flow bioreactor
      indicated preserved and intact hepatocyte morphology and specific function.
      Pulsatile flow culture on PLLA scaffolds is a promising new method of hepatic
      tissue engineering leading to liver neo-tissue formation.

PMID- 16889519
TI  - Mouse adipose-derived stem cells undergo multilineage differentiation in vitro
      but primarily osteogenic and chondrogenic differentiation in vivo.
AB  - Human, rat, and mouse studies have demonstrated the existence of a population of
      adipose-derived adult stem (ADAS) cells that can undergo multilineage
      differentiation in vitro. However, it remains unclear whether these cells
      maintain their multilineage potential in vivo. The aim of this study was to
      examine the in vitro and in vivo characteristics and behavior of a potential
      population of murine ADAS (muADAS) cells isolated from the visceral fat of the
      abdominal cavity of C57BL/10J mice. We used flow cytometry to examine the cells'
      expression of CD29, CD31, CD45, CD34, CD44, CD144, CD146, Flk1, and Sca-1. The
      isolated cell population was CD45 negative, which precludes contamination by
      hematopoietic cells, but was partially positive for Sca-1 and CD34: 2 stem-cell
      markers. After induction in conditioned medium, the muADAS cells gained the
      ability to undergo adipogenic, osteogenic, chondrogenic, myogenic, and
      hematopoietic differentiation in vitro. The muADAS cells readily differentiated
      to form bone and cartilage in vivo for up to 24 weeks, but their ability to
      regenerate muscle or reconstitute bone marrow was found to be limited.

PMID- 16889520
TI  - Small molecule inducers of angiogenesis for tissue engineering.
AB  - Engineering of implantable tissues requires rapid induction of angiogenesis to
      meet the significant oxygen and nutrient demands of cells during tissue repair.
      To this end, our laboratories have utilized medicinal chemistry to synthesize non
      peptide-based inducers of angiogenesis to aid tissue engineering. In this study,
      we describe the evaluation of SC-3-149, a small molecule compound with
      proliferative effects on vascular endothelial cells. Specifically, exogenous
      exposure of SC-3-149 induced an 18-fold increase in proliferation of human
      microvascular endothelial cells in vitro at low micromolar potency by day 14 in
      culture. Moreover, SC-3-149 significantly increased the formation of endothelial
      cord and tubelike structures in vitro, and improved endothelial scratch wound
      healing within 24 h. SC-3-149 also significantly inhibited vascular endothelial
      cell death owing to serum deprivation and high acidity (pH 6). Concurrent
      incubation of SC-3-149 with vascular endothelial growth factor increased cell
      survivability under serum-deprived conditions by an additional 7%. In addition,
      in vivo injection of SC-3-149 into the rat mesentery produced qualitative
      increases in microvessel length density. Taken together, our studies suggest that
      SC-3-149 and its analogs may serve as promising new angiogenic agents for
      targeted drug delivery and therapeutic angiogenesis in tissue engineering.

PMID- 16889521
TI  - Impact of cell type and density on nerve growth factor distribution and
      bioactivity in 3-dimensional collagen gel cultures.
AB  - Local delivery of protein agents is potentially important in many tissue
      engineering systems. In this report, we evaluate an experimental system for
      measuring the rate of nerve growth factor (NGF) transport and biological activity
      within a 3-dimensional, tissue-like environment. Fetal brain cells or PC12 cells
      were suspended throughout collagen gel cultures; controlled-release matrices were
      used to control the spatial and temporal pattern of NGF release. Experimentally
      measured concentration profiles were compared to profiles predicted by a
      mathematical model encompassing diffusion and first-order elimination. Our
      results suggest that NGF moves through gels by diffusion while being eliminated
      at a rate that depends on cell density. Since diffusion and elimination also
      govern protein transport in brain tissue, the collagen gel serves as a model
      system that replicates the main features of transport in the brain and,
      therefore, can be used to identify new strategies that enhance NGF distribution
      in the central nervous system. As an example of the utility of this biophysical
      model, we demonstrate that implantation of multiple controlled-release matrices
      can broaden NGF distribution in gel cultures; this broadening was accompanied by
      a significant increase in cellular biological activity. This approach may be
      useful in customizing NGF distribution throughout degenerating or damaged central
      nervous system tissue while minimizing toxicity to surrounding healthy tissue.

PMID- 16889522
TI  - Myoblast-acellular skeletal muscle matrix constructs guarantee a long-term repair
      of experimental full-thickness abdominal wall defects.
AB  - To obtain a valuable treatment of congenital muscle defect, cell-matrix
      constructs composed of satellite cell-derived myoblasts (XY karyotype) seeded on
      muscle acellular matrices were used to repair a previously created full-thickness
      defect of abdominal wall of 18 1-month-old female Lewis rats. Acellular abdominal
      matrices, obtained by a detergent-enzymatic method, were positive for both basic
      fibroblast growth factor and transforming growth factor-beta, and were able to
      support in vitro cell adhesion. All animals survived the surgery, without signs
      of infection or implant rejection, and were humanely killed at 1, 3, or 9 months
      after surgery. The implants appeared well preserved, were integrated in the host
      tissue, and maintained their original dimension and thickness until 9 months.
      Vesicular acetylcholine transporter was expressed on the surface of muscle fibers
      from 1 month postsurgery. Finally, implanted male myoblasts were present inside
      the patches until 9 months, as demonstrated by the expression of SrY mRNA and by
      the presence of Y chromosome probe signal. These results allow us to conclude
      that cell-matrix constructs could represent a promising approach to the repair of
      muscle defects, because they are repopulated in vivo by skeletal muscle cells and
      nervous elements and maintain their structural integrity over the long term.

PMID- 16889523
TI  - Tissue engineering of flexor tendons: optimization of tenocyte proliferation
      using growth factor supplementation.
AB  - A significant problem in flexor tendon repair is the lack of suitable graft
      material for reconstruction. The ex vivo production of flexor tendon graft
      constructs requires the expansion of primary cells. Growth factors, such as
      platelet-derived growth factor-BB (PDGF-BB), insulin-like growth factor-1 (IGF
      1), and basic fibroblast growth factor (bFGF), are known to promote tendon
      healing and tendon cell proliferation. The purpose of these experiments was to
      optimize tenocyte proliferation in 3 tendon cell populations using growth factor
      supplementation. Cells of the synovial sheath, epitenon, and endotenon were
      isolated from rabbit flexor digitorum profundus tendons and maintained in
      culture. Cell cultures were supplemented with IGF-1, PDGF-BB, and bFGF alone and
      in combination. The conditions used for individual growth factor supplementation
      were IGF-1 (10, 50, and 100 ng/mL), PDGF-BB (1, 10, and 50 ng/mL), and bFGF (0.5,
      1, and 5 ng/mL). The conditions used for combinations of growth factors were IGF
      1 + PDGF-BB (50 + 10 and 100 + 50 ng/mL, respectively) and IGF-1 + PDGF-BB+ bFGF
      (50 + 10 + 1; 50 + 10 + 5; 100 + 50 + 1; and 100 + 50 + 5 ng/mL, respectively).
      For all 3 tendon cell populations, proliferation at 72 h was greater in the
      presence of individual growth factors as compared to controls. With PDGF-BB (50
      ng/mL) supplementation, mean absorbance values increased 97% (0.57 to 1.13) in S
      cells, 37% (0.51 to 0.70) in E cells, and 33% (0.33 to 0.44) in T cells ( p <
      0.001). In addition, a synergistic effect was observed. The combination of growth
      factors resulted in greater proliferation as compared to maximal doses of
      individual growth factors. In cultures supplemented with IGF-1 (100 ng/mL) +PDGF
      BB (50 ng/mL), mean absorbance increased 114% (0.57 to 1.22) in S cells, 63%
      (0.51 to 0.831) in E cells, and 47% (0.33 to 0.48) in T cells ( p < 0.001). IGF-1
      (100 ng/mL) + PDGF-BB (50 ng/mL) + bFGF (5 ng/mL) resulted in the greatest amount
      of cell proliferation for all 3 tendon cell populations. The mean absorbances
      increased 251% in S cells, 98% in E cells, and 106% in T cells ( p < 0.001). In
      summary, IGF-1, PDGF-BB, and bFGF can be used in combination to maximize tenocyte
      proliferation. Synergism among growth factors may provide a means to facilitate
      tendon engineering.

PMID- 16889524
TI  - Biodegradable elastomeric polyurethane membranes as chondrocyte carriers for
      cartilage repair.
AB  - Autologous chondrocyte implantation in combination with an autologous periosteal
      patch has become a clinically accepted procedure for the treatment of articular
      cartilage defects. The use of periosteum has, however, several drawbacks. We have
      been able to fabricate thin elastomeric biodegradable polyurethane (PU) membranes
      that may possibly have an application as a tissue-engineered substitute for the
      periosteal patch. Three types of membranes varying in pore size and surface
      texture were used as substrates for bovine chondrocytes in culture. The
      membranes, marked as P-I, P-II, and P-R, had average pore sizes of 10 to 20
      microm, 40 to 60 microm, and less than 5 microm, respectively. A poly(L/DL
      lactide) 80/ 20% micro-porous membrane (PLA) with an average pore size in the
      range of 10 to 70 microm was used as a control. There was no difference in the
      cell proliferation profile among the 4 membranes. In terms of proteoglycan and
      collagen production, P-I, P-R, and PLA performed similarly to one another. The
      rate of matrix production appears to be greater in the PU membranes than in the
      PLA membrane in the first 10 days, although by day 30, the PLA membrane had
      caught up. In all comparisons, the performance of P-II lagged behind those of the
      other materials. In conclusion, this preliminary study supports the potential use
      of this novel group of PUs as a periosteal flap substitute or perhaps as a
      chondrocyte carrier for matrix-assisted chondrocyte implantation and related
      techniques. Further studies will be necessary to better define their role in
      clinical applications for cartilage repair.

PMID- 16889525
TI  - Cellular and molecular dynamics in the foreign body reaction.
AB  - Intracorporally implanted materials, such as medical devices, will provoke the
      body to initiate an inflammatory reaction. This inflammatory reaction to
      implanted materials is known as the foreign body reaction (FBR) and is
      characterized by 3 distinct phases: onset, progression, and resolution. The FBR
      proceeds in the creation of a dynamic microenvironment that is spatially well
      organized. The progression of the FBR is regulated by soluble mediators, such as
      cytokines, chemokines, and matrix metalloproteinases (MMPs), which are produced
      locally by tissue cells and infiltrated inflammatory cells. These soluble
      mediators orchestrate the cascade of cellular processes in the microenvironment
      that accompanies the FBR, consisting of cellular activation, angiogenesis,
      extravasation, migration, phagocytosis, and, finally, fibrosis. The nature of the
      FBR requires that the soluble mediators act in a spatial and temporally regulated
      manner as well. This regulation is well known for several inflammatory processes,
      but scarce knowledge exists about the intricate relationship between the FBR and
      the expression of soluble mediators. This review discusses the key processes
      during the initiation, progression, and resolution phase, with emphasis on the
      role of soluble mediators. Besides other sites of implantation, we focus on the
      subcutaneous implantation model.

PMID- 16889526
TI  - The chondrocyte: biology and clinical application.
AB  - Chondrocyte is a unique cell type in articular cartilage tissue and is essential
      for cartilage formation and functionality. It arises from mesenchymal stem cells
      (MSCs) and is regulated by a series of cytokine and transcription factor
      interactions, including the transforming growth factor-beta super family,
      fibroblast growth factors, and insulin-like growth factor-1. To understand the
      biomechanisms of the chondrocyte differentiation process, various cellular model
      systems have been employed, such as primary chondrocyte culture, clonal normal
      cell lines (HCS-2/8, Ch-1, ATDC5, CFK-2, and RCJ3.1C5.18), and transformed clonal
      cell lines (T/C-28a2, T/C-28a4, C-28/I2, tsT/AC62, and HPV-16 E6/E7).
      Additionally, cell culture methods, including conventional monolayer culture,
      three-dimensional scaffold culture, bioreactor culture, pellet culture, and organ
      culture, have been established to create stable environments for the expansion,
      phenotypic maintenance, and subsequent biological study of chondrocytes for
      clinical application. Knowledge gained through these study systems has allowed
      for the use of chondrocytes in orthopedics for the treatment of cartilage injury
      and epiphyseal growth plate defects using tissue-engineering approaches.
      Furthermore, the potential of chondrocyte implantation for facial reconstruction,
      the treatment of long segmental tracheal defects, and urinary incontinence and
      vesicoureteral reflux are being investigated. This review summarizes the present
      study of chondrocyte biology and the potential uses of this cell in orthopedics
      and other disciplines.

PMID- 16889527
TI  - Effects of electromagnetic stimulation on calcified matrix production by SAOS-2
      cells over a polyurethane porous scaffold.
AB  - There is increasing interest in designing new biomaterials that could potentially
      be used in the form of scaffolds as bone substitutes. In this study we used a
      hydrophobic crosslinked polyurethane in a typical tissue-engineering approach,
      that is, the seeding and in vitro culturing of cells using a porous scaffold.
      Using an electromagnetic bioreactor (magnetic field intensity, 2 mT; frequency,
      75 Hz), we investigated the effect of the electromagnetic stimulation on SAOS-2
      human osteoblast proliferation and calcified matrix production. Cell
      proliferation was twice as high; expression of decorin, osteocalcin, osteopontin,
      type I collagen, and type III collagen was greater (1.3, 12.2, 12.1, 10.0, and
      10.5 times as great, respectively); and calcium deposition was 5 times as great
      as under static conditions without electromagnetic stimulation. RT-PCR analysis
      revealed the electromagnetically upregulated transcription specific for decorin,
      fibronectin, osteocalcin, osteopontin, transforming growth factor-beta, type I
      collagen, and type III collagen. The immunolocalization of the extracellular
      matrix constituents showed their colocalization in the cell-rich areas. The
      bioreactor and the polyurethane foam were designed to obtain cell colonization
      and calcified matrix deposition. This cultured biomaterial could be used, in
      clinical applications, as an osteoinductive implant for bone repair.

PMID- 16889528
TI  - Functional analysis of encapsulated hepatic progenitor cells.
AB  - A major challenge in developing therapies based on progenitor or stem cell
      populations (from sources other than bone marrow) involves developing a mode to
      deliver these cells in a manner that optimizes their viability, engraftment,
      proliferation, and differentiation. We have previously isolated a hepatic
      progenitor cell (HPC) population from adult liver tissue that differentiates into
      hepatic and biliary cell subtypes. We postulated that, using electrostatic
      encapsulation, we could reproducibly generate an ex vivo environment for the
      HPCs. We also theorized that this approach would foster cellular viability and
      function of the progenitor cell population. Using this encapsulation process, we
      consistently produced beads with uniform diameters between 200 and 700 microm. In
      vitro analysis of the encapsulated beads demonstrated extended periods of
      viability and function based on albumin production, urea metabolism, and glycogen
      storage. In conclusion, HPC encapsulation fosters the subsequent differentiation
      of HPCs into functional cells while maintaining their viability in long-term
      culture. These results demonstrate the efficacy of this method using somatic
      derived progenitor cell populations and pave the way for clinical therapies.

PMID- 16889530
TI  - Antibiotics reduce the growth rate and differentiation of embryonic stem cell
      cultures.
AB  - Embryonic stem cells (ESCs) are being investigated increasingly for their
      potential as a cell source for tissue engineering. Antibiotics are regularly used
      in ESC culture media to control contamination, although they can be cytotoxic and
      interfere with protein synthesis. Our aim was to examine the effects of the
      frequently used antibiotics gentamicin and combined penicillin and streptomycin
      on ESC culture using differentiation of murine ESC into type II pneumocytes as a
      model. Antibiotics reduced the expression of the specific marker for type II
      pneumocytes, SPC mRNA, by up to 60%. We also identified an adverse effect on the
      growth rate of differentiating embryoid bodies, causing a significant ( p < 0.05)
      reduction of up to 40%, and an increase in population doubling time of up to 48%.
      No contamination was seen in any of the cultures. Our findings suggest that the
      routine use of antibiotics in ESC culture should be avoided as it may reduce the
      efficiency of the culture system.

PMID- 16889529
TI  - Chondrogenic differentiation on perlecan domain I, collagen II, and bone
      morphogenetic protein-2-based matrices.
AB  - Extracellular matrix (ECM) molecules in cartilage cooperate with growth factors
      to regulate chondrogenic differentiation and cartilage development. Domain I of
      perlecan (Pln) bears heparan sulfate chains that bind and release heparin binding
      growth factors (HBGFs). We hypothesized that Pln domain I (PlnDI) might be
      complexed with collagen II (P-C) fibrils to improve binding of bone morphogenetic
      protein-2 (BMP-2) and better support chondrogenesis and cartilage-like tissue
      formation in vitro. Our results showed that P-C fibrils bound more BMP-2 than
      collagen II fibrils alone, and better sustained BMP-2 release. Polylactic acid
      (PLA)-based scaffolds coated with P-C fibrils immobilized more BMP-2 than either
      PLA scaffolds or PLA scaffolds coated with collagen II fibrils alone.
      Multipotential mouse embryonic mesenchymal cells, C3H10T1/2, were cultured on 2
      dimensional P-C fibrils or 3-dimensional P-C/BMP-2-coated (P-C-B) PLA scaffolds.
      Chondrogenic differentiation was indexed by glycosaminoglycan (GAG) production,
      and expression of the pro-chondrogenic transcription factor, Sox9, as well as
      cartilaginous ECM proteins, collagen II, and aggrecan. Immunostaining for
      aggrecan, perlecan, tenascin, and collagen X revealed that both C3H10T1/2 cells
      and primary mouse embryonic fibroblasts cultured on P-C-B fibrils showed the
      highest expression of chondrogenic markers among all treatment groups. Safranin O
      Fast Green staining indicated that cartilage-like tissue was formed in the P-C-B
      scaffolds, while no obvious cartilage-like tissue formed in other scaffolds. We
      conclude that P-C fibrils provide an improved biomimetic material for the binding
      and retention of BMP-2 and support chondrogenic differentiation.

PMID- 16889531
TI  - Functions of vitamin D, retinoic acid, and dexamethasone in mouse adipose-derived
      mesenchymal cells.
AB  - Adipose-derived mesenchymal cells (AMCs) offer great promise for tissue
      engineering of bone. Previously, 1,25-dihydroxyvitamin D3, retinoic acid (RA),
      and dexamethasone had been shown to promote osteogenesis in bone marrow-derived
      mesenchymal cells (BMSCs). To study the osteogenic characteristics of mouse AMCs,
      we applied these 3 hormones alone and in combination to the AMCs and examined
      markers of osteogenic differentiation. Interestingly, vitamin D and RA
      demonstrated a consistent, dose-dependent enhancement of osteogenesis and
      upregulated osteoblast specific markers including osteopontin and osteocalcin.
      However, in AMCs, dexamethasone clearly inhibited osteogenic differentiation in a
      dose dependent fashion and greatly increased the adipogenic marker peroxisome
      proliferator activated receptor gamma (PPAgamma). In summary, we show in vitro
      that vitamin D and RA are potential candidates to serve as enhancers of
      osteogenesis of AMCs and may be incorporated into future cell-based strategies
      for bone tissue engineering.

PMID- 16889532
TI  - Contact with existing adipose tissue is inductive for adipogenesis in matrigel.
AB  - The effect of adipose tissue on inductive adipogenesis within Matrigel (BD
      Biosciences) was assessed by using a murine chamber model containing a vascular
      pedicle. Three-chamber configurations that varied in the access to an adipose
      tissue source were used, including sealed- and open-chamber groups that had no
      access and limited access, respectively, to the surrounding adipose tissue, and a
      sealed-chamber group in which adipose tissue was placed as an autograft. All
      groups showed neovascularization, but varied in the amount of adipogenesis seen
      in direct relation to their access to preexisting adipose tissue: open chambers
      showed strong adipogenesis, whereas the sealed chambers had little or no adipose
      tissue; adipogenesis was restored in the autograft chamber group that contained 2
      to 5-mg fat autografts. These showed significantly more adipogenesis than the
      sealed chambers with no autograft ( p < 0.01). Autografts with 1mg of fat were
      capable of producing adipogenesis but did so less consistently than the larger
      autografts. These findings have important implications for adipose tissue
      engineering strategies and for understanding de novo production of adipose
      tissue.

PMID- 16889537
TI  - ACE gene insertion/deletion polymorphism modulates capillary permeability in
      hypertension.
AB  - A D/D (deletion/deletion) polymorphism within the ACE (angiotensin 1-converting
      enzyme) gene increases the risk of microalbuminuria, a predictor of
      atherosclerotic vascular disease, in essential hypertension. It is unknown,
      however, whether this genetic profile is accompanied by disturbed macromolecular
      permeability of systemic capillary endothelium, possibly in the context of
      generalized endothelial dysfunction. In the present study, the ACE gene
      polymorphism was determined by PCR in 79 never-treated uncomplicated hypertensive
      men and 16 normotensive men as controls. Evaluation variables were TERalb
      (transcapillary escape rate of albumin; the 1-h decline rate of intravenous
      (125)I-albumin, a measure of integrity of systemic capillary endothelium),
      albuminuria and forearm vasodilation to intra-arterial acetylcholine, an index of
      NO (nitric oxide)-mediated vasomotion, in addition to a series of sensitive
      parameters of albumin permeation (blood pressure, metabolic status and smoking
      habits). Analyses were done by comparing D/D homozygotes with grouped I/D
      (insertion/deletion) and I/I (insertion/insertion) subjects. TERalb was higher in
      D/D hypertensives, who had higher albuminuria, more frequent microalbuminuria and
      comparable forearm responsiveness to intra-arterial acetylcholine. Fasting
      glucose and insulin, insulin sensitivity, 24-h blood pressure, smoking habits and
      metabolic parameters did not differ between the two groups. TERalb and urine
      albumin values were positively associated in the hypertensive subjects. In
      conclusion, ACE D/D homozygosis, independently of several confounding factors,
      associates with higher TERalb in men with essential hypertension. This may
      reflect noxious genetic influences on systemic vascular permeability, a critical
      control mechanism for atherogenesis in the absence of grossly impaired NO
      mediated arteriolar responsiveness. The parallel behaviour of TERalb and
      albuminuria suggests some shared genetically mediated determinant of renal and
      systemic microvascular abnormalities in hypertension.

PMID- 16889538
TI  - Histologic findings from positive crossmatch or ABO-incompatible renal
      allografts: accomodation or chronic allograft injury?

PMID- 16889539
TI  - An appraisal of tolerance in liver transplantation.
AB  - Human liver allografts have a lower susceptibility to rejection than other
      organs. In addition, in some liver transplant recipients immunosuppressive drugs
      can be completely withdrawn, and these patients are considered as 'operationally'
      tolerant. Careful scrutiny of accumulated clinical experience indicates that
      elective immunosuppressive drug weaning is feasible in almost 20% of selected
      liver transplant recipients. This is associated with an incidence of 12% to 76%
      of acute cellular rejection, but these episodes are commonly mild and often
      resolve by return to baseline immunosuppression (IS), many times without the need
      to administer steroid boluses. Study of tolerance in liver transplantation (LT)
      has been hampered by confusion regarding the definitions of rejection and
      tolerance, and by the absence of prospective studies correlating results of
      immune monitoring assays and clinical outcome. Thus, we lack a clinically
      validated treatment-stopping rule capable of predicting the success of IS
      withdrawal and this procedure has to be performed on a 'trial and error' basis.
      The search for an accurate means to identify allograft tolerance among
      immunosuppressed recipients should become a priority in LT research. This
      information would provide a biological basis for guiding IS withdrawal protocols
      and for the implementation of tolerance-promoting strategies in LT.

PMID- 16889540
TI  - CD4+25+ regulatory T cells limit Th1-autoimmunity by inducing IL-10 producing T
      cells following human lung transplantation.
AB  - Chronic human lung allograft rejection is manifested by bronchiolitis obliterans
      syndrome (BOS). BOS has a multifactorial etiology. Previous studies have
      indicated that both cellular and humoral alloimmunity play a significant role in
      the pathogenesis of BOS. Recently, autoimmunity has also been demonstrated to
      contribute to lung allograft rejection in animal models. However, the
      significance of autoimmunity in BOS remains unknown. In this report, we
      investigated the role of naturally occurring CD4(+)CD25(+) regulatory T cells (T
      regs) in modulating cellular autoimmunity to collagen type V (col-V), a
      'sequestered' yet immunogenic self-protein present in the lung tissue, following
      lung transplantation (LT). We demonstrated that col-V reactive CD4(+) T cells
      could be detected in the peripheral blood of lung transplant recipients. There
      was a predominance of IL-10 producing T cells (T(IL-10)) reactive to col-V with
      significantly lower levels of IFN-gamma and IL-2 producing T cells (Th1 cells).
      The col-V specific T(IL-10) cells suppressed the proliferation and expansion of
      col-V specific Th1 cells by IL-10-dependent and contact-independent pathways. The
      T(IL-10) cells were distinct but their development was dependent on the presence
      of T-regs. Furthermore, during chronic lung allograft rejection there was a
      significant decline of T(IL-10) cells with concomitant expansion of col-V
      specific IFN-gammaproducing Th1 cells.

PMID- 16889541
TI  - TGF-beta inhibition of CTL re-stimulation requires accessory cells and induces
      peroxisome-proliferator-activated receptor-gamma (PPAR-gamma).
AB  - Effective cellular immunity to Epstein-Barr virus (EBV), necessary to prevent or
      cure many post-transplant lymphoproliferative disorders (PTLD), can be inhibited
      by transforming growth factor-beta (TGF-beta). In vitro, TGF-beta inhibits memory
      CTL re-stimulation from whole PBMC. We show that the effect of TGF-beta on CTL re
      stimulation is not directly on the T cell, but requires an accessory cell (AC)
      population. Further, pre-treatment of AC with TGF-beta significantly reduces
      memory CTL re-stimulation and suppresses delayed type hypersensitivity (DTH)
      responses. Addition of exogenous interferon-gamma to the AC overcomes the effects
      of TGF-beta. TGF-beta pre-treatment also up-regulates expression of peroxisome
      proliferator-activated receptor-gamma (PPAR-gamma) in CD14(+) AC. Importantly,
      pre-treatment of AC with the PPAR-gamma ligand, ciglitazone, results in
      significantly reduced memory CTL re-stimulation. Thus, the effects of TGF-beta in
      this system may be mediated in part via PPAR-gamma, and PPAR-gamma activation
      could have significant inhibitory effects on memory T-cell responses by affecting
      AC function. These data have important implications in understanding how memory
      CTL are re-stimulated and function to prevent disease, especially PTLD.

PMID- 16889542
TI  - C4d and C3d staining in biopsies of ABO- and HLA-incompatible renal allografts:
      correlation with histologic findings.
AB  - Biopsies of ABO-incompatible and positive crossmatch (HLA-incompatible) renal
      allografts were retrospectively examined to compare results of C4d and C3d
      staining, and the correlation between such staining and histologic findings
      suggestive of antibody-mediated rejection (AMR). A total of 75 biopsies (55
      protocol, 17 for graft dysfunction, 3 for other indications) of 24 ABO
      incompatible grafts and 244 biopsies (103 protocol, 129 for graft dysfunction, 12
      for other indications) of 66 HLA-incompatible grafts were examined; all were
      stained for C4d and approximately 40% for C3d. In ABO-incompatible grafts, 80% of
      protocol biopsies and 59% performed for graft dysfunction showed C4d staining in
      peritubular capillaries (PTC); this staining was not correlated with neutrophil
      margination in PTC. In HLA-incompatible grafts, PTC C4d was present in 26% of
      protocol biopsies and 60% of biopsies for graft dysfunction; 92% of biopsies with
      >1+ (0-4+ scale), diffuse PTC C4d had > or =1+ margination and/or thrombotic
      microangiopathy (TMA), compared with 12% of C4d-negative biopsies. C3d was
      somewhat more predictive of margination than C4d in ABO-incompatible, but not HLA
      incompatible, grafts. In summary, while PTC C4d deposition indicates probable AMR
      in biopsies of HLA-incompatible grafts, including protocol biopsies, there is no
      histologic evidence that C4d deposition is correlated with injury in most ABO
      incompatible grafts.

PMID- 16889543
TI  - Outcomes of donor evaluations for adult-to-adult right hepatic lobe living donor
      liver transplantation.
AB  - The purpose of this study is to determine the role of liver biopsy and outcome of
      patients undergoing donor evaluation for adult-to-adult right hepatic lobe living
      donor liver transplantation (LDLT). Records of patients presenting for a
      comprehensive donor evaluation between 1997 and February 2005 were reviewed.
      Liver biopsy was performed only in patients with risk factors for abnormal
      histology. Two hundred and sixty patients underwent a comprehensive donor
      evaluation and 116 of 260 (45%) were suitable for donation, 14 of 260 (5.4%) did
      not complete evaluation and 130 of 260 (50%) were rejected. Four patients
      underwent unsuccessful hepatectomy surgery due to discovery of intraoperative
      abnormalities. Between 1997 and 2001, the acceptance rate of donor candidates
      (63%) was higher than 2002-2005 (36%), p < 0.0001. Sixty-six of the 150 eligible
      patients (44%) fulfilled criteria for liver biopsy and 28 of 66 (42%) had an
      abnormal finding. Less than half of the patients undergoing donor evaluation were
      suitable donors and the donor acceptance rate has declined over time. A large
      proportion of the patients undergoing liver biopsy have abnormal findings. Our
      evaluation process failed to identify 4 of 103 who had aborted donor surgeries.

PMID- 16889544
TI  - Prevalence and risk factors for diabetes mellitus in moderate term survivors of
      liver transplantation.
AB  - The prevalence and risk factors for diabetes mellitus after liver transplantation
      are not well understood. Thus, we sought to identify independent risk factors for
      the development of diabetes after liver transplantation using currently accepted
      medical criteria. We studied the prevalence and risk factors in 253 adult
      recipients transplanted at UCLA between January 1998 and December 2002. Analysis
      of the retrospective data was performed using demographic, immunosuppression and
      liver disease variables. Factors found to be significant on a univariate analysis
      were further studied in a multivariate analysis. There were 158 men and 95 women
      in our study. The mean age was 51.4 +/- 11.0 years. The mean [+/- standard
      deviation (SD) pretransplant body mass index was 26.7 (+/-5.1). Most patients
      were transplanted for hepatitis C (HCV). The prevalence of diabetes after
      transplantation was 17.8%. In a multivariate analysis only gender [odds ratio
      (OR) = 0.37; p = 0.02] was independently predictive of the development of
      diabetes. This study in a large liver transplant recipient population identifies
      male gender as an independent risk factor for the development of diabetes. Follow
      up studies are needed to assess the impact of diabetes, and its intervention on
      post-transplant morbidity and mortality.

PMID- 16889545
TI  - A randomized trial of exercise and dietary counseling after liver
      transplantation.
AB  - We report results of a randomized clinical trial of a combined intervention of
      exercise and dietary counseling (ExD) after orthotopic liver transplantation
      (OLT). Of the 151 patients randomized into ExD or usual care (UC), 119 completed
      testing 2, 6 and 12 months post-OLT. Testing included assessment of exercise
      capacity (VO(2peak)), quadricep muscle strength, body composition (DXA),
      nutritional intake (Block 95) and health-related quality of life (SF-36). The
      intervention consisted of individualized counseling and follow-up to home-based
      exercise and dietary modification. Repeated measure ANOVA was performed to
      determine differences over time between ExD and UC with a secondary analysis to
      determine differences over time between adherers (Adh), nonadherers (Nadh) to the
      intervention and UC. The ExD group showed greater increases in VO(2peak) (p =
      0.036), and self-reported general health (p = 0.038) compared to UC. Both groups
      demonstrated increases in muscle strength, body weight, body fat and other SF-36
      scale scores. Adherence to the intervention was 37% with positive trends in
      VO(2peak) and body composition observed in Adh compared to Nadh and UC. These
      data suggest improvements in exercise capacity and body composition are achieved
      with nutrition and exercise behavior modifications initiated early after OLT and
      with regular follow-up.

PMID- 16889546
TI  - CMV-IVIG for prevention of Epstein Barr virus disease and posttransplant
      lymphoproliferative disease in pediatric liver transplant recipients.
AB  - A randomized controlled trial of CMV-IVIG (cytomegalovirus-intravenous
      immunoglobulin) for prevention of Epstein Barr virus (EBV) posttransplant
      lymphoproliferative disease (PTLD) in pediatric liver transplantation (PLTx)
      recipients was begun in Pittsburgh and subsequently expanded to four additional
      sites. Protocol EB viral loads were obtained in a blinded fashion; additional
      loads could be obtained for clinical indications. Patients were followed for 2
      years post-LTx. Eighty-two evaluable patients (39 CMV-IVIG, 43 placebo) developed
      18 episodes of EBV disease (7 CMV-IVIG, 11 placebo) including nine cases of PTLD
      (three CMV-IVIG, six placebo). No significant differences were seen in the
      adjusted 2-year EBV disease-free rate (CMV-IVIG 79%, placebo 71%) and PTLD-free
      rate (CMV-IVIG 91%, placebo 84%) between treatment and placebo groups at 2 years
      (p > 0.20). The absence of significant effect of CMV-IVIG may be explained by a
      lack of efficacy of the drug or limitations of sample size.

PMID- 16889547
TI  - The effect of reflux and bile acid aspiration on the lung allograft and its
      surfactant and innate immunity molecules SP-A and SP-D.
AB  - Gastro-esophageal reflux and related pulmonary bile acid aspiration were
      prospectively investigated as possible contributors to postlung transplant
      bronchiolitis obliterans syndrome (BOS). We also studied the impact of aspiration
      on pulmonary surfactant collectin proteins SP-A and SP-D and on surfactant
      phospholipids--all important components of innate immunity in the lung. Proximal
      and distal esophageal 24-h pH testing and broncho-alveolar lavage fluid (BALF)
      bile acid assays were performed prospectively at 3-month posttransplant in 50
      patients. BALF was also assayed for SP-A, SP-D and phospholipids expressed as
      ratio to total lipids: phosphatidylcholine; dipalmitoylphosphatidylcholine;
      phosphatidylglycerol (PG); phosphatidylinositol; sphingomyelin (SM) and
      lysophosphatidylcholine. Actuarial freedom from BOS was assessed. Freedom from
      BOS was reduced in patients with abnormal (proximal and/or distal) esophageal pH
      findings or BALF bile acids (Log-rank Mantel-Cox p < 0.05). Abnormal pH findings
      were observed in 72% (8 of 11) of patients with bile acids detected within the
      BALF. BALF with high levels of bile acids also had significantly lower SP-A, SP
      D, dipalmitoylphosphatidylcholine; PG and higher SM levels (Mann-Whitney, p <
      0.05). Duodeno-gastro-esophageal reflux and consequent aspiration is a risk
      factor for the development of BOS postlung transplant. Bile acid aspiration is
      associated with impaired lung allograft innate immunity manifest by reduced
      surfactant collectins and altered phospholipids.

PMID- 16889548
TI  - Trajectories of change in quality of life in 12-month survivors of lung or heart
      transplant.
AB  - Survival and functional outcomes for lung transplant recipients continue to lag
      behind those for heart recipients. Whether these poorer physical outcomes
      translate into poorer quality of life (QOL) for lung recipients relative to heart
      recipients is unknown. Lung versus heart transplant recipients' perceptions of
      QOL were longitudinally compared at three time-points across the first year
      posttransplant. Additionally, potentially important predictors of patient QOL
      were examined. Adult transplant recipients (N = 199) participated in semi
      structured interviews that included measures of QOL, optimism, mastery, social
      support, religiosity and coping. Temporal patterns of QOL change were compared
      between lung and heart recipients who survived until 1 year posttransplant using
      mixed-model, hierarchical analysis of variance (ANOVA). Demographic and
      psychosocial predictors were examined with multiple regression analysis to
      identify the unique effects of each variable on QOL 1 year posttransplant. While
      heart recipients' QOL across several domains was higher shortly after transplant,
      lung patients' QOL improved and was equivalent to that of heart recipients by 1
      year posttransplant. Greater optimism and support from friends predicted better
      QOL in physical, psychological and social domains. Conversely, avoidant coping
      strategies predicted poorer physical functioning. Thus, while clinical
      interventions designed to improve QOL posttransplant should be tailored to
      transplant recipients' initial psychosocial assets and liabilities, they need not
      be distinguished by transplant type.

PMID- 16889549
TI  - Favorable long-term outcome after liver-kidney transplant for recurrent hemolytic
      uremic syndrome associated with a factor H mutation.
AB  - A male child initially presented with atypical hemolytic uremic syndrome (HUS) at
      the age of 4 months and progressed within weeks to end stage renal disease
      (ESRD). At the age of 2 years he received a live-related kidney transplant from
      his mother, which, despite initial good function, was lost to recurrent disease
      after 2 weeks. Complement factor H analysis showed low serum levels and the
      presence of two mutations on different alleles (c.2918G > A, Cys973Tyr and
      c.3590T > C, Val1197Ala). His survival on dialysis was at risk because of access
      failure and recurrent bacteremic episodes. Therefore, at the age of 5 years he
      received a combined liver-kidney transplant with pre-operative plasma exchange.
      Initial function of both grafts was excellent and this has been maintained for
      over 2 years. This report suggests that despite setbacks in previous experience,
      combined liver-kidney transplantation offers the prospect of a favorable long
      term outcome for patients with HUS associated with complement factor H mutations.

PMID- 16889550
TI  - Reverse diastolic intrarenal flow due to calcineurin inhibitor (CNI) toxicity.
AB  - Renal calcineurin inhibitor (CNI) toxicity is a frequent side effect of
      immunosuppression with CNIs in solid organ transplantation, leading to acute and
      chronic renal failure. Acute CNI toxicity is due to vasoconstriction of the vasa
      afferens and efferens and vacuolization of smooth muscle cells with medial
      hyalinosis, leading to vessel lumen narrowing. Our case had an acute renal
      failure 8 months after deceased donor kidney transplantation under treatment with
      tacrolimus, sirolimus and prednisolone. In Doppler sonography, we observed
      reverse diastolic intrarenal blood flow, reflecting intense vessel narrowing.
      There were histological signs of acute CNI toxicity. Within days of reducing the
      tacrolimus trough level, renal function improved markedly and Doppler sonography
      showed orthograde intrarenal blood flow. This is the first case of functional,
      Doppler sonographic evidence for CNI-induced, rapidly reversible narrowing of
      intrarenal vessels. This case illustrates the potential role of tacrolimus and
      sirolimus dosing in combination therapy to produce severe intrarenal
      vasoconstriction.

PMID- 16889551
TI  - Ureteral reconstruction and bladder augmentation using intestinal allograft in a
      modified multivisceral transplant patient.
AB  - Segments of ileum are used as conduits following ureteral resection and for
      bladder augmentation to achieve adequate bladder capacity. We herein report the
      use of a segment of transplanted ileum for this purpose in a patient with
      Gardner's syndrome who underwent multivisceral transplantation. To our knowledge
      this is the first such case report.

PMID- 16889552
TI  - Successful kidney transplantation from donor with Marfan's syndrome.
AB  - Marfan's syndrome is caused by mutations in the extracellular matrix protein
      fibrillin-1 with aortic aneurysm and dissection being its most life-threatening
      manifestations. Kidney transplantation from donors with Marfan's syndrome has
      never been reported in the literature, possibly because of reticences due to the
      underlying connective tissue disease. Here, we report two patients with end-stage
      renal disease, transplanted with the kidneys from a donor with Marfan's syndrome
      who died of aortic dissection and cerebral hemorrhage. After delayed graft
      function in both recipients, renal function normalized with no renovascular
      complications and negative proteinuria for 6 years in one patient and 2 years in
      the other patient, who died from an ischemic cerebrovascular insult. Kidneys from
      organ donors with Marfan's syndrome might be suitable for transplantation.

PMID- 16889553
TI  - Cardiovascular magnetic resonance imaging has much to offer in the assessment of
      renal transplant recipients.

PMID- 16889556
TI  - PTLD visualization by FDG-PET: improved detection of extranodal localizations.

PMID- 16889557
TI  - Update on the pathophysiology and classification of von Willebrand disease: a
      report of the Subcommittee on von Willebrand Factor.
AB  - von Willebrand disease (VWD) is a bleeding disorder caused by inherited defects
      in the concentration, structure, or function of von Willebrand factor (VWF). VWD
      is classified into three primary categories. Type 1 includes partial quantitative
      deficiency, type 2 includes qualitative defects, and type 3 includes virtually
      complete deficiency of VWF. VWD type 2 is divided into four secondary categories.
      Type 2A includes variants with decreased platelet adhesion caused by selective
      deficiency of high-molecular-weight VWF multimers. Type 2B includes variants with
      increased affinity for platelet glycoprotein Ib. Type 2M includes variants with
      markedly defective platelet adhesion despite a relatively normal size
      distribution of VWF multimers. Type 2N includes variants with markedly decreased
      affinity for factor VIII. These six categories of VWD correlate with important
      clinical features and therapeutic requirements. Some VWF gene mutations, alone or
      in combination, have complex effects and give rise to mixed VWD phenotypes.
      Certain VWD types, especially type 1 and type 2A, encompass several
      pathophysiologic mechanisms that sometimes can be distinguished by appropriate
      laboratory studies. The clinical significance of this heterogeneity is under
      investigation, which may support further subdivision of VWD type 1 or type 2A in
      the future.

PMID- 16889558
TI  - When it comes to von Willebrand disease, does 1 + 1 = 3?

PMID- 16889559
TI  - Muscle metabolism in patients with polymyositis simultaneously evaluated by using
      31P-magnetic resonance spectroscopy and near-infrared spectroscopy.
AB  - Simultaneous measurements of muscle energy metabolism using (31)P-magnetic
      resonance spectroscopy ((31)P-MRS) and the kinetics of muscular oxygen metabolism
      using near-infrared spectroscopy (NIRS) were conducted in polymyositis (PM)
      patients. The subjects were 12 PM patients (age 45 +/- 12 years) and 12 normal
      controls (age 41 +/- 12 years). The muscle phosphocreatine (PCr) index and
      intracellular pH (pHi) were determined with (31)P-MRS and the changes in
      intramuscular oxygenated (oxy-Hb), deoxygenated (deoxy-Hb), and total haemoglobin
      (total Hb) were evaluated with NIRS . The pHi and PCr index before steroid
      therapy in PM patients were significantly lower during exercise than in normal
      controls, and their recovery was statistically significantly delayed compared
      with the controls. The pattern of changes in NIRS over time before steroid
      therapy in PM patients differed from that in normal controls. There were smaller
      changes in deoxy-Hb and oxy-Hb during exercise, and total Hb decreased during
      exercise. In contrast, the kinetics of muscular metabolism after steroid therapy
      showed changes similar to those seen in normal controls. Simultaneous (31)P-MRS
      and NIRS measurements to determine the kinetics of muscular metabolism are
      expected to be useful as a noninvasive approach for the evaluation of treatment
      effects in PM patients.

PMID- 16889560
TI  - The survival and function of baboon red blood cells, platelets, and plasma
      proteins: a review of the experience from 1972 to 2002 at the Naval Blood
      Research Laboratory, Boston, Massachusetts.
AB  - The studies reported in this monograph were performed between 1972 and 2002 when
      it was possible to study healthy male and female baboons. A colony of baboons was
      maintained for 30 years without any adverse events observed in these baboons in
      the numerous studies that were performed. These protocols were reviewed and
      approved by the institutional animal care and use committees (IACUC) at the sites
      where the studies were performed and by the veterinarian services of the U.S.
      Navy's Bureau of Medicine and Surgery, the Office of Naval Research, and the
      Department of Defense. The physiology of red blood cells (RBCs), platelets
      (PLTs), and plasma proteins in the baboon was investigated together with the
      viability and function of preserved RBCs, PLTs, and plasma proteins. These
      studies in the baboon could not have been performed in normal volunteers and
      patients. The data obtained have provided critical information to explain the
      clinical observations reported in normal volunteers and patients after
      transfusion of fresh and preserved blood products. These studies were supported
      by the U.S. Navy's Bureau of Medicine and Surgery and the Office of Naval
      Research. In addition, the support of the late Congressman J. Joseph Moakley from
      Massachusetts is acknowledged because without his support many of these studies
      could not have been performed. The authors acknowledge the contributions of the
      numerous research collaborators identified in the 52 peer-reviewed publications
      that cite other funding agencies that supported the research that is reported,
      the editorial assistance of Ms Cynthia Ann Valeri, and the assistance of Ms
      Deborah Tattersall who prepared the figures and tables reported in this
      publication.

PMID- 16889562
TI  - Abstracts of the 42nd Annual Scientific Meeting of the Australian and New Zealand
      Society of Nephrology. August 14-18, 2006. Melbourne, Australia.

PMID- 16889563
TI  - Impact of off-pump coronary artery bypass surgery on postoperative renal
      dysfunction: current best available evidence.
AB  - Renal dysfunction is a serious complication after coronary artery bypass surgery
      with cardiopulmonary bypass. Cardiopulmonary bypass-related non-pulsatile flow,
      hypothermia, haemolysis, systemic inflammatory reactions and emboli are mentioned
      as possible causes for this postoperative renal dysfunction. In an attempt to
      avoid these deleterious effects of cardiopulmonary bypass, off-pump coronary
      artery bypass surgery has been rediscovered. Resurgence of interest in off-pump
      coronary artery bypass surgery is associated with the expectation that avoiding
      deleterious effects of the cardiopulmonary bypass leads to better outcomes and
      possibly decreased costs and resource use. We are currently practising in an era
      of evidence-based medicine that mandates the prospective randomized controlled
      trial as the most accurate tool for determining a treatment benefit compared with
      a control population. The present review article attempts to evaluate the current
      best available evidence from randomized controlled trials on the impact of off
      pump coronary artery bypass surgery on postoperative renal dysfunction.

PMID- 16889564
TI  - Role of podocyte slit diaphragm as a filtration barrier.
AB  - Although the role of glomerular basement membrane has been emphasised as the
      barrier for retaining plasma proteins in the past three decades, some recent
      studies have demonstrated that the slit diaphragm of the glomerular epithelial
      cell (podocyte) is the structure likely to be the barrier in the glomerular
      capillary wall. Nephrin and podocin were identified as gene products mutated in
      Finnish-type congenital nephrotic syndrome and autosomal recessive steroid
      resistant nephrotic syndrome, respectively. Nephrin s located at the outer
      leaflet of plasma membranes of the slit diaphragm. Podocin is reported to have an
      interaction with nephrin. The anti-nephrin antibody is capable of inducing
      massive proteinuria, which indicates that nephrin is a key functional molecule in
      the slit diaphragm. The expression of nephrin and podocin was reduced in
      glomeruli of minimal change nephrotic syndrome, which suggested that the altered
      expression of these molecules contributes to the development of proteinuria also
      in acquired diseases. Some recent studies demonstrated that CD2-associated
      protein (CD2AP) is also a functional molecule in the slit diaphragm, and its
      expression is altered in membranous nephropathy. These observations suggested
      that alteration of the molecular arrangement in the slit diaphragm is involved in
      the development of proteinuria in several kinds of glomerular diseases.

PMID- 16889565
TI  - Rhabdomyolysis following laparoscopic radical nephrectomy: a case to heighten
      awareness.
AB  - Rhabdomyolysis, myoglobinuria and acute renal failure are rare complication of
      surgery. Long operative time, increased body mass, lateral decubitus positioning
      and extracellular volume depletion may predispose to this condition. The authors
      describe the case of a 70-year-old man with renal cell carcinoma who underwent a
      laparoscopic right radical nephrectomy in the lateral decubitus position. His
      postoperative course was complicated by acute renal failure due to
      rhabdomyolysis. Heightened awareness, early recognition and treatment of this
      condition are important, particularly as laparoscopic nephrectomy is becoming a
      common procedure for living donor transplantation.

PMID- 16889566
TI  - Bioartificial kidney in the treatment of acute renal failure associated with
      sepsis.
AB  - Acute renal failure (ARF) associated with sepsis has a high rate of mortality. It
      is not merely a surrogate marker for severity of disease but also an independent
      predictor of mortality and a separate pathogenic entity, even when nearly
      physiological doses of fluid and small-molecule clearance are maintained with
      currently available renal replacement therapies (RRT). The techniques to remove
      cytokines, including high-volume haemofiltration, haemodialysis using high-cut
      off haemofilters, and absorptive techniques, lead to some improvement in outcome
      but are still insufficient to reverse the complicated biological dysregulation
      resulting from ARF associated with sepsis. The novel and exciting technique of
      cell therapy, which is based on the principle of using functional cells to
      replace a greater range of renal functions, may add significant benefit to
      current RRT in dealing with this disease process. Because renal tubule cells
      appear to play critical roles in immunoregulation, renal tubule cell therapy
      during ARF associated with sepsis should alter the detrimental multiple-organ
      consequences of sepsis. The development of a bioartificial kidney consisting of a
      conventional haemofiltration cartridge in series with a renal tubule assist
      device containing renal proximal tubule cells represents a new therapeutic
      approach to this clinical disorder. The results to date of large animal studies
      and recent Phase I/II and Phase II clinical trials show that such a device
      replaces multiple kidney functions and modifies the sepsis condition to improve
      survival in ARF.

PMID- 16889567
TI  - Residual renal function and dialysis modality: is it really beneficial to
      preserve residual renal function in dialysis patients?
AB  - Residual renal function (RRF) contributes to the achievement of treatment
      adequacy in stage 5 chronic kidney disease (CKD-5) patients. It may facilitate
      patients' acceptance of renal replacement therapy (RRT) in allowing reduction of
      treatment time duration and minimising dietary and fluid restriction. It has been
      confirmed to improve dialysis patient outcomes. Attempts to preserve RRF in
      incident Stage 5 chronic kidney disease patients are still subject to intense
      controversies in the nephrology community. The aim of this review is to analyse
      the role of renal replacement modalities in the maintenance of RRF in dialysis
      patients. Under the scope of this manuscript, four questions are explored: Is the
      preservation of residual renal function an objective for dialysis adequacy? Does
      dialysis modality affect the decline of RRF? What are the factors implicated by
      this loss of RRF? At what expense can the maintenance of RRF be achieved in
      dialysis patients? Preservation of RRF is undoubtedly an interesting means to
      enhance the efficacy of renal replacement therapy and reduce dietary fluid
      restriction but it should not be considered as a goal of dialysis adequacy in
      dialysis patients. Further, preservation of RRF must be considered as a permanent
      trade-off between patient comfort and chronic fluid volume overload.

PMID- 16889568
TI  - Preventing catheter-related infections with antibiotic lock solutions: are we
      spoilt for choice?

PMID- 16889569
TI  - Enhancing the survival of tunneled haemodialysis catheters using an antibiotic
      lock in the elderly: a randomised, double-blind clinical trial.
AB  - BACKGROUND: Tunneled-cuffed catheters (TCC) are often used among the elderly to
      commence and carry out haemodialysis (HD). Complications like infection and
      thrombosis frequently reduce the lifespan of TCC. The role of an antibiotic
      heparin 'lock' in the prevention of thrombotic and infectious complications and
      enhancement of TCC survival in the elderly has not been investigated previously.
      METHODS: In this prospective, double-blind clinical trial, TCC (n = 119, placed
      among 113 elderly patients requiring HD during March 2002 - February 2003) were
      randomised to either group I having TCC (n = 59, placed in 58 elderly patients)
      locked with cefotaxime (10 mg/mL) and heparin (5000 U/mL), or group II with TCC
      (n = 60, placed in 55 elderly patients) having catheter-restricted filling of
      heparin (5000 U/mL) alone. Symptomatic catheter-related blood stream infections
      (CRBSI) and catheter thrombosis were the primary end points in this study.
      Thrombosis was defined as an inability to use the catheter at a blood flow of 200
      mL/min that did not respond to catheter repositioning and/or intraluminal
      thrombolysis. The incidence of catheter thrombosis, CRBSI and percentage of
      catheter survival were estimated and statistically compared between the two
      groups. RESULTS: Kaplan-Meier survival analysis using log rank test showed higher
      thrombosis-free TCC survival (84.7%vs 63.3%, P = 0.021), infection-free survival
      (68.7%vs 31.3%, P < 0.001) and infection and thrombosis-free survival (65.0%vs
      35.0%, P = 0.006) at 365 days in group I compared with group II. CONCLUSION:
      Cefotaxime and heparin locks safely and effectively enhance the lifespan of TCC
      by lowering the incidence of thrombotic and infectious complications among
      elderly end-stage renal failure (ESRD) patients.

PMID- 16889570
TI  - Novel renoprotective actions of erythropoietin: new uses for an old hormone.
AB  - Erythropoietin (EPO) has been used widely for the treatment of anaemia associated
      with chronic kidney disease and cancer chemotherapy for nearly 20 years. More
      recently, EPO has been found to interact with its receptor (EPO-R) expressed in a
      large variety of non-haematopoietic tissues to induce a range of cytoprotective
      cellular responses, including mitogenesis, angiogenesis, inhibition of apoptosis
      and promotion of vascular repair through mobilization of endothelial progenitor
      cells from the bone marrow. Administration of EPO or its analogue, darbepoetin,
      promotes impressive renoprotection in experimental ischaemic and toxic acute
      renal failure, as evidenced by suppressed tubular epithelial apoptosis, enhanced
      tubular epithelial proliferation and hastened functional recovery. This effect is
      still apparent when administration is delayed up to 6 h after the onset of injury
      and can be dissociated from its haematological effects. Based on these highly
      encouraging results, at least one large randomized controlled trial of EPO
      therapy in ischaemic acute renal failure is currently underway. Preliminary
      experimental and clinical evidence also indicates that EPO may be renoprotective
      in chronic kidney disease. The purpose of the present article is to review the
      renoprotective benefits of different protocols of EPO therapy in the settings of
      acute and chronic kidney failure and the potential mechanisms underpinning these
      renoprotective actions. Gaining further insight into the pleiotropic actions of
      EPO will hopefully eventuate in much-needed, novel therapeutic strategies for
      patients with kidney disease.

PMID- 16889571
TI  - L-carnitine ameliorates doxorubicin-induced nephrotic syndrome in rats.
AB  - AIM: Effects of L-carnitine on nephrotoxicity and oxidative stress induced by
      doxorubicin (DOX) in rats were investigated. METHODS: The rats were divided into
      four groups: group 1, control (0.9% NaCl); group 2, DOX injection (7.5 mg/kg,
      i.v.); group 3, DOX plus low dose (40 mg/kg) L-carnitine; and group 4, DOX plus
      high dose (200 mg/kg) L-carnitine. L-carnitine was administered 1 h before
      doxorubicin injection and daily thereafter for 15 days. RESULTS: Rats in group 2
      were associated with hypoalbuminaemia, hyperlipidaemia, high urinary excretion of
      protein and elevated plasma creatinine and urea nitrogen. The glomerular
      filtration rate (GFR) and effective renal plasma flow (ERPF) decreased with
      increased renal vascular resistance (RVR). Kidney catalase (CAT) activity was
      decreased. In group 3 and 4, plasma triglyceride and cholesterol declined. L
      carnitine improved renal functions by elevated GFR and ERPF and decreased plasma
      creatinine and urea nitrogen. The kidney CAT activity were increased
      significantly compared with group 2. From histopathological results, group 2 rats
      were found to have glomerular capillary dilation and tubular dilation. The
      lesions were less in group 3 and 4 rats. CONCLUSION: L-carnitine can protect
      renal impairment functionally, biochemically and histopathologically with a
      corresponding reduction of oxidative stress.

PMID- 16889572
TI  - Prevention programmes of progressive renal disease in developing nations.
AB  - Development of strategies for the early detection and prevention of non
      communicable diseases, including kidney disease, is the only realistic strategy
      to avert an imminent global health and economic crisis and enhance equity in
      health care worldwide. In this article, we briefly examine the burden of non
      communicable diseases, including diabetes, hypertension, cardiovascular disease
      and how chronic kidney disease (CKD) represents a key integrated element in the
      setting, even in developing countries. A possible explanation of the increasing
      number of people who have or are at risk to develop CKD in poor countries is also
      given. A survey of major screening and intervention programmes performed or
      ongoing globally is then presented, highlighting differences and hurdles of
      projects planned in developed or developing nations as well as in unprivileged
      communities in developed countries. Finally, some recommendations on future steps
      to implement prevention programmes in emerging worlds are provided.

PMID- 16889573
TI  - Markers of inflammation and atherosclerosis in Egyptian patients with systemic
      lupus erythematosus.
AB  - BACKGROUND: Cardiovascular events are markedly increased in systemic lupus
      erythematosus (SLE) and the mechanism of atherogenesis remains poorly understood.
      Low-grade inflammation and endothelial dysfunction play pivotal roles in the
      initiation, progression and propagation of the atherosclerotic process. Several
      methods have been employed to assess endothelial function, among them the
      measurement of biomarkers of endothelial activation and dysfunction
      (intercellular adhesion molecule (ICAM)-1). Since then, it has been reported that
      such biomarkers play a more important role than traditional risk factors in
      cardiovascular disease. OBJECTIVE: To measure (tumour necrosis factor (TNF)
      alpha, interleukin (IL)-6 and ICAM-1) levels as markers of inflammation and
      atherosclerosis in 40 Egyptian patients with SLE with various degrees of activity
      in comparison with 20 healthy volunteers, and to investigate their relationship
      to disease activity and hypertension. METHODS: Sixty subject (40 with SLE and 20
      healthy controls) were the subject of this study, their clinical disease activity
      was scored according to the SLE Disease Activity Index (SLEDAI), and serum
      sampling was obtained for TNF-alpha, IL-6 and ICAM-1 level assay. Renal biopsy
      was carried out and examined by light microscopy. The mean level of TNF-alpha, IL
      6 and ICAM-1 were significantly higher in SLE patients with active disease
      (766.95 +/- 357.82 Pg/mL, 135.4 +/- 54.23 Pg/mL, 826.05 +/- 367.1 Pg/mL) when
      compared with those with inactive disease (314.01 +/- 100.87 Pg/mL, 47.33 +/-
      18.61 pg/mL, 441.33 +/- 225.19 Pg/mL) and healthy control volunteers (172.7 +/-
      39.19 Pg/mL, 21.15 +/- 10.99 Pg/mL, 111.5 +/- 17.36 Pg/mL), respectively.
      Furthermore, these levels were significantly higher in hypertensive (614.08 +/-
      333.05 Pg/mL, 107.86 +/- 54.96 Pg/mL and 862.13 +/- 333.29 Pg/mL) compared to
      normotensive patients (267.5 +/- 112.72 Pg/mL, P = 0.008, 35.75 +/- 20.26 Pg/mL,
      P = 0.02I, and 337.25 +/- 235.62 Pg/mL, P = 0.02) for TNF-alpha, IL-6 and ICAM,
      respectively. There were no statistically significant difference regarding age,
      sex, smoking, cholesterol and high-density lipoprotein (HDL) levels between
      hypertensive and normotensive patients. CONCLUSION: A high concentration of
      soluble ICAM-1 in Egyptian patients with SLE and nephritis is reported here for
      the first time. Our finding of increased concentrations of TNF-alpha, IL-6 and
      ICAM-1 in Egyptian patients with SLE and lupus nephritis underlines the
      importance of inflammation and endothelial involvement in this disorder, but
      their predictive value in the disease monitoring needs to be further studied.

PMID- 16889574
TI  - Clinical characteristics of patients with segmental renal infarction.
AB  - BACKGROUND: Renal infarction is usually an underestimated disease due to its rare
      and non-specific presentations; the renal survival of these patients is not well
      studied. The aim of the present analysis is to study the clinical features and
      outcome in patients who had documented renal infarction. METHODS: Twenty-two
      patients (12 men and 10 women, mean age of 57.7 +/- 3.44 years (28.4-83.3 years))
      with image-confirmed segmental renal infarction in the past 15 years were
      enrolled. All patients were followed up at outpatient department with a median of
      4 years (1-14 years). Initial and follow-up clinical characteristics and
      laboratory results were recorded. RESULTS: The most common underlying disease was
      cardiovascular disease. Renal infarction often presented with non-specific
      symptoms, including flank pain (55%), vague abdominal pain (50%), nausea/vomiting
      (46%) and fever (27%). The levels of leucocytes, lactate dehydrogenase, blood
      urea nitrogen and serum creatinine were all elevated at admission. The early
      diagnosis group (12/22) had more obvious flank pain, nausea/vomiting (P < 0.001)
      and higher alanine transaminase (P = 0.02). It also predisposed to undergo
      antiplatelet or anticoagulant therapy (all P < 0.04). During follow up, there was
      no recurrence in the whole study group, and a trend of better recovery of renal
      function was noted in the early diagnosis group. CONCLUSION: The serum creatinine
      level correlates with longer hospitalization length (P < 0.05). As regards long
      term prognosis, no definite factor or treatment was found to have significant
      effect in segmental renal infarction patients. However, early diagnosis and early
      initiation of treatment seems to have a positive effect on future renal outcome.

PMID- 16889575
TI  - Biosimilars: how similar or dissimilar are they?
AB  - The imminent expiry of patents on biological medicinal products, such as epoetin
      alfa in 2006, has significant implications for nephrology in Australia. The
      purpose of this review is to examine the differences between biosimilars (similar
      biological medicinal products) and generic low molecular weight (chemical) drugs.
      The approach that regulatory agencies, including the European Medicines Agency
      (EMEA) and the Therapeutic Goods Administration (TGA), are taking towards
      biosimilars is also discussed. Biosimilars differ from generic chemical drugs in
      many important ways, including the size and complexity of the active substance,
      the nature of the starting materials (cell banks, tissues and other biological
      products), and the complexity of the manufacturing processes. Therefore, it has
      been acknowledged by the EMEA that established legal and regulatory principles of
      'essential similarity' that are applied to standard chemical generics cannot be
      readily applied to biosimilars. One of the key areas of concern with the
      introduction of biosimilars into the field of nephrology will be guaranteeing the
      safety and efficacy of biosimilars. New manufacturers will need to ensure that
      their biopharmaceutical has a similar efficacy and safety profile to the
      innovator product through more extensive clinical trials than the limited testing
      done for generic versions of low molecular weight chemical medicines.

PMID- 16889576
TI  - Prevalence and risk factors of undetected proteinuria in an elderly South-East
      Asian population.
AB  - BACKGROUND: Urinalysis is not a standard component of health screening in the
      elderly population. OBJECTIVE: We investigated the prevalence and risk factors of
      undetected renal disease as defined by proteinuria (PR) in an elderly South-East
      Asian population. METHOD: There were 19,848 participants of age >or=65 years in
      National Kidney Foundation's Nationwide Screening programme at Singapore. Mean
      age was 70.6 +/- 5.3 years. After excluding the 1.1% who had pre-existing renal
      disease, 8.5% were identified to have previously undetected PR defined as >or=1+
      protein on urine dipstick analysis. Multivariate regression revealed that male
      gender (OR = 1.2, reference category (Ref): female), known diabetes (odds ratio
      (OR) = 2.28; P < 0.0001), hypertension (OR = 1.62; P = 0.0001), presence of
      elevated blood pressure (BP) (>or=120/90 mmHg) on screening (OR = 1.38, 1.89,
      3.45 for mild, moderate and severe BP, respectively, all P < 0.0001), elevated
      body mass index (BMI) (OR = 1.3 for BMI >or=23 vs BMI < 23 kg/m(2)), and smoking
      (OR = 1.2, ref: non-smokers) were significantly associated with PR. Finally, a
      progressive increase in OR for PR was observed with stepwise increase in age
      (years) (OR for 67-68.9: 1.2, P = 0.025; 69-72.9, 1.49, P = 0.49; >or=73: 1.56, P
      < 0.0001, Ref: 65-66.9 years). CONCLUSION: We conclude that there is high
      prevalence of previously undetected proteinuria in elderly South-East Asians.
      Because proteinuria is a risk factor for cardiovascular disease, our findings
      support inclusion of urinalysis in routine health screening for this population.

PMID- 16889578
TI  - Gout in renal transplant recipients.
AB  - AIMS: The aims of the present audit were to determine the prevalence of gout in
      renal transplant recipients in Canterbury, New Zealand, to identify risk factors
      for gout, and to assess the range of treatments used, their efficacy and
      complications. In addition, the authors wished to assess the impact of post-renal
      transplant gout on the patient. METHODS: Patients with post-transplantation gout
      were identified from the Christchurch Hospital Nephrology database. For each
      patient with gout a post-renal transplantation recipient without gout post
      transplant was found matched for age, sex and date of transplant. Case notes were
      audited and patients interviewed. RESULTS: In total, 47/202 (23%) living renal
      transplant recipients had gout post transplant. Those patients with gout were
      more likely to be taking a loop diuretic (68%vs 34%, P < 0.001), to have a higher
      serum urate and impaired renal function and to have had gout prior to the
      transplant. Of those patients who developed gout post transplant 70% had an
      attack at least every 3 months. Of those who returned to work post transplant 48%
      required time off work because of gout. CONCLUSION: out is an important problem
      in the post-transplant population causing significant morbidity and time off
      work. Diuretics, impaired renal function, gout prior to transplantation and
      hyperuricaemia are important risk factors. The need for diuretic therapy should
      be kept under review in these patients. Hypouricaemic therapy should be
      considered early in those who develop gout post renal transplantation. Further
      studies are required to determine whether treatment for asymptomatic
      hyperuricaemia is justified.

PMID- 16889577
TI  - Review of Epstein-Barr virus and post-transplant lymphoproliferative disorder
      post-solid organ transplantation.
AB  - Post-transplant lymphoproliferative disorder (PTLD) following solid organ
      transplantation is an important form of post-transplant malignancy. PTLD is
      typically associated with Epstein-Barr virus (EBV) and occurs in the setting of
      profound immunosuppression resulting in a deficiency of EBV-specific cytotoxic T
      lymphocytes (CTL). Predisposing factors include EBV mismatch between donor and
      recipient, use of immunosuppression especially T-cell depletive therapies and
      genetic predisposition of recipients. The standard approach has been to reduce
      immunosuppression but is often insufficient to induce tumour regression. Further
      understanding of the immunobiology of PTLD has resulted in improved monitoring
      techniques (including EBV viral load determined by polymerase chain reaction) and
      newer treatment options. Recent work has highlighted a potential role for
      dendritic cells in both the pathogenesis and treatment of PTLD. Current treatment
      modalities include adoptive immunotherapy using ex vivo generated autologous EBV
      specific CTL or allogeneic CTL, cytokine therapies, antiviral agents, and more
      recently, rituximab and dendritic-cell based therapies. This review focuses on
      the developments and progress in the pathogenesis, diagnosis and treatment of
      PTLD.

PMID- 16889579
TI  - Subcapsular collection of glomerular filtrate: rare form of page kidney.

PMID- 16889580
TI  - Spontaneous gluteus muscle haematoma in a haemodialysis patient.

PMID- 16889581
TI  - Thrombotic microangiopathy in a patient with anti-glomerular basement membrane
      antibody disease.

PMID- 16889582
TI  - mTOR inhibitors in ADPKD.

PMID- 16889584
TI  - Depression is the core of suicidality--its treatment is the cure.

PMID- 16889585
TI  - Prospective studies of suicidal behavior in major depressive and bipolar
      disorders: what is the evidence for predictive risk factors?
AB  - OBJECTIVE: Prospective studies over the past 30 years have identified an array of
      predictive indicators for suicidal acts in mood disorders. However, prediction of
      suicidal behavior remains an elusive goal. This paper reviewed evidence from
      prospective studies for clinical factors that elevate risk of suicidal acts in
      that group. METHOD: English language prospective studies of suicidal behavior in
      major depressive and bipolar disorders were examined. RESULTS: The predictors
      with the best support were a past history of suicidal behavior and the presence
      of refractory or recurrent depressions. For other risk factors, there was either
      not enough data to consider them robust or findings were contradictory.
      CONCLUSION: Future studies must not only be comprehensive in their inclusion of
      potentially contributing factors, but must also address their relative importance
      towards the goal of developing predictive models and enhance suicide prevention
      efforts.

PMID- 16889586
TI  - Increased antidepressant use and fewer suicides in Jamtland county, Sweden, after
      a primary care educational programme on the treatment of depression.
AB  - OBJECTIVE: To consider and evaluate a continuing medical education programme for
      general practitioners (GPs) on depression in Jamtland county, Sweden, inspired by
      the Gotland study. METHOD: Interactive seminars were conducted between 1995 and
      2002 in Jamtland county. For evaluation, suicide rates and annual sales
      statistics of antidepressants were compared with national averages.
      Questionnaires were used for information about attitudes and prescribing habits.
      RESULTS: The suicide rate in Jamtland decreased to the same level as the national
      average. The use of antidepressants increased from 25% below the Swedish average
      to the same level. The selective serotonin re-uptake inhibitors (SSRIs) were
      preferred because of their tolerability. Suicide issues were considered to be
      most important in the management of depressed patients. CONCLUSION: A trend
      towards a greater prescription of antidepressants and fewer suicides after an
      educational programme on depression for GPs replicated the findings from the
      Gotland study. The educational programme will be conducted annually and could be
      a model for other regions.

PMID- 16889587
TI  - Temporal changes in suicide rates for persons treated and not treated with
      antidepressants in Denmark during 1995-1999.
AB  - OBJECTIVE: To compare the temporal changes in suicide rate among patients treated
      with antidepressants with the change in suicide rate among persons who have not
      been treated with antidepressants during 1995-1999. METHOD: In a historic
      prospective national pharmacoepidemiological register linkage study by using four
      Danish registers we included 438,625 patients who had purchased antidepressants,
      and compared them with 1,199,057 population based control persons. The annual
      rate of suicide was estimated using Poisson regression analyses. RESULTS: The
      suicide rate decreased for persons treated with antidepressants as well as for
      persons not treated with antidepressants. The proportion of persons, who
      committed suicide and who had not been treated with antidepressants decreased.
      The reduction in suicide rate was more pronounced among persons treated with
      SSRIs or older antidepressants than among persons not treated with
      antidepressants. CONCLUSION: Several factors contribute to the decreasing suicide
      rate. The most pronounced decrease in suicide rate was found among persons
      treated with antidepressants.

PMID- 16889588
TI  - Understanding suicidal ideation in psychosis: findings from the Psychological
      Prevention of Relapse in Psychosis (PRP) trial.
AB  - OBJECTIVE: To examine the clinically important phenomenon of suicidal ideation in
      psychosis in relation to affective processes and the multidimensional nature of
      hallucinations and delusions. METHOD: In a cross-sectional study of 290
      individuals with psychosis, the associations between level of suicidal ideation,
      affective processes, positive symptoms, clinical and demographic variables were
      examined. RESULTS: Forty-one per cent of participants expressed current suicidal
      ideation. Suicidal ideation was associated with depressed mood, anxiety, low self
      esteem, negative illness perceptions, negative evaluative beliefs about the self
      and others and daily alcohol consumption. Frequency of auditory hallucinations
      and preoccupation with delusions were not associated with suicidal ideation;
      however, positive symptom distress did relate to suicidal thoughts. CONCLUSION:
      Affective dysfunction, including distress in response to hallucinations and
      delusions, was a key factor associated with suicidal ideation in individuals with
      psychotic relapse. Suicidal ideation in psychosis appears to be an
      understandable, mood-driven process, rather than being of irrational or
      'psychotic' origin.

PMID- 16889589
TI  - Clinical correlates of DHEA associated with post-traumatic stress disorder.
AB  - OBJECTIVE: Increased plasma dehydroepiandrosterone (DHEA) and
      dehydroepiandrosterone-sulfate (DHEAS) have been demonstrated in post-traumatic
      stress disorder (PTSD), but the documented beneficial effects of these steroids
      in enhancing mood and cognition, as well as neuroprotection, suggest their
      presence in PTSD may be associated with defensive rather than maladaptive
      effects. METHOD: We, therefore, examined plasma DHEA, DHEAS, cortisol, and the
      DHEA/cortisol ratio in 40 male veterans with or without PTSD, and determined
      their relationships to PTSD symptom severity and symptom improvement. RESULTS:
      The PTSD group showed significantly higher plasma DHEA and non-significantly
      higher DHEAS levels as well as a significantly lower cortisol/DHEA ratio,
      controlling for age. Regression analyses demonstrated that DHEA and DHEAS levels
      could be predicted by symptom improvement and coping, whereas the cortisol/DHEA
      ratio was predicted by severity of childhood trauma and current symptom severity.
      CONCLUSION: That greater symptom improvement was related to DHEA levels may
      suggest for a role for these hormones in modulating recovery from PTSD.

PMID- 16889590
TI  - Predictors of psychological distress in survivors of the 1999 earthquakes in
      Turkey: effects of relocation after the disaster.
AB  - OBJECTIVE: Relocations after disasters are known to cause added distress in
      survivors. This study examined the effects of migration and other factors on
      psychological status of survivors 4 years after the two severe earthquakes in
      Turkey. METHOD: Five hundred and twenty-six adult survivors of the 1999
      earthquakes currently living in Ankara were given self-report measures assessing
      traumatic stress, depression, earthquake experience and social support. RESULTS:
      The rates of current post-traumatic stress disorder (PTSD) and depression were
      25% and 11%, respectively. Although both traumatic stress and depression factors
      were predicted by some demographic and trauma severity variables, relocation
      status predicted depression but not traumatic stress. CONCLUSION: The rates of
      psychological distress were higher than expected in a city considered to be safe
      in terms of earthquake risk. Relocation after the disaster may increase
      psychological distress by disrupting the social network.

PMID- 16889591
TI  - The effect of temperament and character on response to selective serotonin
      reuptake inhibitors in panic disorder.
AB  - OBJECTIVE: In this prospective study, temperament and character were evaluated in
      patients with panic disorder (PD), before 1 year of medication therapy, to verify
      whether these factors influenced the outcome of treatment. METHOD: Seventy-one PD
      patients were evaluated with the SCID-IV, the Temperament and Character Inventory
      (TCI), the SCL-90, the Ham-A and the Ham-D. Patients were treated with
      pharmacotherapy and were evaluated monthly over 1 year. RESULTS: Before
      treatment, non-remitted patients showed higher levels of harm avoidance (HA) and
      lower levels of persistence (P), self-directedness (SD) and cooperativeness (C),
      whereas remitted patients showed only higher levels of HA. After controlling the
      effect of the confounding variables, the likelihood to achieve remission was
      positively related to SD score (OR = 1.12; P = 0.002), particularly 'self
      acceptance' SD dimension (OR = 1.30; P = 0.02). CONCLUSIONS: Our data suggest
      that in PD: i) the evaluation of personality, using the Cloninger's model,
      confirms the presence of personality pathology as one predictor of non-response
      to treatment; ii) in patients with low SD a combination of medication and
      cognitive-behaviour therapy should be the most effective treatment.

PMID- 16889592
TI  - Regulation of alpha7-nicotinic receptor subunit and alpha7-like gene expression
      in the prefrontal cortex of patients with bipolar disorder and schizophrenia.
AB  - OBJECTIVE: The alpha7-nicotinic receptor subunit gene (CHRNA7) is located at
      chromosome 15q13-14, a region previously linked with schizophrenia. Genetic
      association and mRNA expression studies also implicate CHRNA7 in schizophrenia.
      The CHRNA7 gene has a partial duplication that constitutes the alpha7-like
      nicotinic receptor gene (CHRFAM7A). We hypothesized that major psychoses could
      affect the expression of both CHRNA7 and CHRFAM7A. METHOD: CHRNA7 and CHRFAM7A
      mRNA levels were measured in postmortem prefrontal cortex (donated by the Stanley
      Foundation) from subjects with schizophrenia, bipolar disorder and unaffected
      controls (n = 35 each). RESULTS: The mRNA levels of alpha7 and alpha7-like genes
      have a positive correlation overall (r = 0.25; P = 0.009), however, there is no
      significant difference in the expression of CHRNA7 among the three diagnostic
      groups. CONCLUSION: This correlation is driven by the bipolar group (r = 0.43; P
      = 0.009), and is absent in schizophrenia and unaffected controls, suggesting an
      alteration in the CHRNA7:CHRFAM7A ratio in bipolar disorder.

PMID- 16889593
TI  - Bright light therapy for seasonal affective disorder in Israel (latitude 32.6
      degrees N): a single case placebo-controlled study.
AB  - INTRODUCTION: We describe a patient diagnosed as having seasonal affective
      disorder (SAD, winter depression), an unlikely condition in Israel (latitude 32.6
      degrees N), a country with relatively minor daylight photoperiodic changes
      between seasons. METHOD: Case report. RESULTS: A 46-year-old woman with a
      clinical picture of depression (Diagnostic and Statistical Manual of Mental
      Disorders diagnostic criteria for 'major depression with seasonal pattern')
      reacted positively to 3 weeks of daily bright light therapy of 10,000 lux/wide
      spectrum. She was asked to wear dark sunglasses during placebo sessions to
      accommodate an A-B-C single-case-design. The intervention resulted in an
      improvement of 74-80% in the Hamilton anxiety and depression scales (clinician
      rated) and the Beck depression inventory, similar to results obtained in high
      latitude regions. The depression and anxiety levels returned close to baseline
      levels following 1 week of the placebo intervention. CONCLUSION: Seasonal
      affective disorder is apparently not limited to certain latitudes. The effect of
      light therapy was short-lived after discontinuation of the treatment, with rapid
      relapse occurring in the placebo phase.

PMID- 16889596
TI  - Evaluation of islet transplantation from non-heart beating donors.
AB  - We evaluated islet transplantation from non-heart beating donors (NHBDs) with our
      Kyoto Islet Isolation Method. All patients had positive C-peptide after
      transplantation. The average HbA(1C) levels of the five recipients significantly
      improved from 7.8 +/- 0.4% at transplant to 5.2 +/- 0.2% currently (p < 0.01).
      Three patients with no or a single autoantibody became insulin independent while
      the other two patients with double autoantibodies reduced their insulin
      requirement but did not become insulin independent. C-peptide in patients who
      became insulin-independent gradually increased after each transplantation whereas
      C-peptide in patients who did not become insulin-independent from 3 months after
      the first transplantation to the next transplantation dramatically decreased. The
      beta-score of the three patients who became insulin independent was the best of
      eight. In conclusion, our method makes it feasible to use NHBDs for islet
      transplant into type 1 diabetic patients efficiently.

PMID- 16889597
TI  - Direct versus indirect allorecognition: Visualization of dendritic cell
      distribution and interactions during rejection and tolerization.
AB  - Interactions of donor and recipient dendritic cells (DCs) with CD4+ T cells
      determine the alloantigenic response in organ transplantation, where recipient T
      cells respond either directly to donor MHC, or indirectly to processed donor MHC
      allopeptides in the context of recipient MHC molecules. The present study
      evaluates donor and recipient alloantigen-presenting DC trafficking and their
      interactions with CD4+ T cells in the lymph nodes (LNs) and the spleen under
      tolerogenic treatment with anti-CD2 plus anti-CD3 mAb compared with untreated
      rejecting conditions. CX3CR1(GFP) BALB/c (I-A(d)) donor hearts were transplanted
      into C57BL/6 (I-A(b)) mice and quantification of donor DC direct (GFP+ or I
      A(d+)) and recipient DC indirect (YAe+) trafficking and interactions with host
      CD4+ T cells was performed by fluorescent microscopy. Our data indicate that
      although both direct and indirect interactions between CD4+ T cells and donor and
      recipient DCs occur shortly after engraftment, only indirect presentation
      persists in the LN, but not the spleen, of tolerized recipients. These data
      suggest that distinct anatomic lymphoid compartments play a critical role in
      peripheral tolerance induction and maintenance, and persistent indirect
      presentation to CD4+ T cells within the LNs is an important process during
      tolerization.

PMID- 16889598
TI  - Impact of recipient MELD score on resource utilization.
AB  - The model for end stage liver disease (MELD) system prioritizes deceased donor
      organs to the sickest patients who historically require higher healthcare
      expenditures. Limited information exists regarding the association of recipient
      MELD score with resource use. Adult recipients of a primary liver allograft (n =
      222) performed at a single center in the first 27 months of the MELD system were
      analyzed. Costs were obtained for each recipient for the 12 defined categories of
      resource utilization from the time of transplant until discharge. True
      (calculated) MELD scores were used. Inpatient transplant costs were significantly
      associated with recipient MELD score (r = 0.20; p = 0.002). Overall 1-year
      patient survival was 85.0% and was not associated with MELD score (p = 0.57, log
      rank test). Recipient MELD score was significantly associated with costs for
      pharmacy, laboratories, radiology, dialysis and physical therapy. Multivariate
      linear regression revealed that MELD score was most strongly associated with cost
      compared to other demographic and clinical factors. Recipient MELD score is
      correlated with transplant costs without significantly impacting survival.

PMID- 16889599
TI  - Monitoring of human cytomegalovirus-specific CD4 and CD8 T-cell immunity in
      patients receiving solid organ transplantation.
AB  - Absolute and human cytomegalovirus (HCMV)-specific CD4+ and CD8+ T-cell counts
      were monitored in 38 solid organ (20 heart, 9 lung and 9 kidney) transplant
      recipients during the first year after transplantation by a novel assay based on
      T-cell stimulation with HCMV-infected autologous dendritic cells. According to
      the pattern of T-cell restoration occurring either within the first month after
      transplantation or later, patients were classified as either early (n = 21) or
      late responders (n = 17). HCMV-specific CD4+ and CD8+ T-cell counts were
      consistently lower in late compared to early responders from baseline through 6
      months after transplantation. In addition, in late responders, while HCMV
      infection preceded immune restoration, HCMV-specific CD4+ restoration was
      significantly delayed with respect to CD8+ T-cell restoration. The number of HCMV
      specific CD4+ and CD8+ T-cells detected prior to transplantation significantly
      correlated with time to T-cell immunity restoration, in that higher HCMV-specific
      T-cell counts predicted earlier immune restoration. Clinically, the great
      majority of early responders (18/21, 85.7%) underwent self-resolving HCMV
      infections (p = 0.004), whereas the great majority of late responders (13/17,
      76.5%) were affected by HCMV infections requiring antiviral treatment (p =
      <0.0001). Simultaneous monitoring of HCMV infection and HCMV-specific T-cell
      immunity predicts T-cell-mediated control of HCMV infection.

PMID- 16889600
TI  - Long-term outcome of adult-to-adult living donor liver transplantation for post
      Kasai biliary atresia.
AB  - Our objective was to analyze problems in the perioperative management and long
      term outcome of living donor liver transplantation (LDLT) for biliary atresia
      (BA). Many reports have described the effectiveness of liver transplantation (LT)
      for BA, particularly in pediatric cases, but little information is available
      regarding LT in adults (> or =16 years old). Between June 1990 and December 2004,
      464 patients with BA underwent LDLT at Kyoto University Hospital, of whom 47
      (10.1%) were older than 16 years. In this study, we compared the outcomes between
      adult (> or =16 years old) and pediatric (<16 years old) patients. The incidence
      of post-transplant intestinal perforation, intra-abdominal bleeding necessitating
      repeat laparotomy and biliary leakage was significantly higher (p < 0.0001,
      <0.001 and <0.001, respectively) in adults. Overall cumulative 1-, 5- and 10-year
      survival rates in pediatric patients were significantly higher (p < 0.005) than
      in adults. Two independent prognostic determinants of survival were identified: a
      MELD score over 20 and post-transplant complications requiring repeat laparotomy.
      Outcome of LDLT in adult BA patients was poorer than in pediatric patients. It
      seems likely that LT will be the radical treatment of choice for BA and that LDLT
      should be considered proactively at the earliest possible stage.

PMID- 16889601
TI  - Composite tissue allograft extends a helping hand to transplant immunologists.
AB  - The first successful human hand transplantation, performed on September 1998, has
      translated the scope of 'composite tissue allotransplantation' from research
      concepts into clinical practice. Beyond microsurgical problems that have been
      overcome several years ago, the main obstacle that still prevents the
      generalization of composite tissue allotransplantation is immunologic. This
      review, which summarizes the evidence obtained both from experimental animal
      models and from the first recipients of a hand transplant, is focused on the two
      immunological characteristics of composite allografts that set them apart from
      other solid organ allografts: (i) they contain skin tissue that elicits a strong
      immune response; and (ii) they contain lymphoid tissues (such as bone marrow and
      lymph nodes) that have the potential both to attack the recipient, and also to
      down-modulate the host immune response and induce tolerance. While on one hand,
      the composite tissue allografts raise new challenges to transplant immunologists,
      on the other they provide answers to questions that have remained unresolved for
      a long time. In this sense, composite tissue allografts extend a helping hand to
      transplant immunologists.

PMID- 16889602
TI  - Acute oxalate nephropathy: A new etiology for acute renal failure following
      nonrenal solid organ transplantation.
AB  - Acute renal insufficiency (ARI) is a frequent complication of nonrenal solid
      organ transplantation and may be responsible for an unfavorable outcome,
      particularly if dialysis is required. The etiology of post-transplantation ARI is
      poorly understood, with only isolated clinical cases being reported, most imputed
      to drug toxicity. We report here, the first three observations of irreversible
      ARI associated with acute oxalate nephropathy (AON) in the course of nonrenal
      organ transplants: a lung transplant and a lung-liver transplant in two patients
      with mucoviscidosis, and a cardiac transplant. The diagnosis of AON was made
      histologically. In all three cases, the ARI supervened after prolonged
      consumption of antibiotics capable of interfering with the colonic flora, and
      leading to enteric hyperoxaluria. The recognition of AON as a cause of post
      transplantation, ARI underlines hyperoxaluria and digestive hyperabsorption of
      oxalate as specific risk factors for AON and should permit better posttransplant
      care of these patients.

PMID- 16889603
TI  - Iatrogenic amyloid neuropathy in a Japanese patient after sequential liver
      transplantation.
AB  - A 57-year-old woman in Japan, the first recipient of part of a liver from a 58
      year-old man with familial amyloidotic polyneuropathy (FAP) amyloidogenic
      transthyretin Val30Met who had had sensorimotor polyneuropathy in the lower limbs
      for 3 years, started to develop sensory neuropathy 7 years after transplantation.
      Before the July 1998 sequential transplantation, she had been in a hepatic coma
      at the terminal stage of primary biliary cirrhosis and waiting for deceased donor
      liver transplantation. In September 2004, biopsy samples of her duodenum first
      showed amyloid deposition. Although biopsy materials in 2005 and 2006 showed no
      changes in amyloid deposition, decreased temperature sensation and pain in
      fingertips and toes were detected at a neurologic examination in March 2006.
      Thus, clinical symptoms of FAP appeared about 2 years after amyloid deposition
      started. Nerve conduction velocity studies revealed mild to moderate axonal
      sensory polyneuropathy without demyelination. Our findings confirmed iatrogenic
      sensory neuropathy induced by amyloid deposition 7 years after sequential liver
      transplantation.

PMID- 16889604
TI  - Redox-active iron released during machine perfusion predicts viability of
      ischemically injured deceased donor kidneys.
AB  - Redox-active iron, catalyzing the generation of reactive oxygen species, has been
      implicated in experimental renal ischemia-reperfusion injury. However, in
      clinical transplantation, it is unknown whether redox-active iron is involved in
      the pathophysiology of ischemic injury of non-heart-beating (NHB) donor kidneys.
      We measured redox-active iron concentrations in perfusate samples of 231 deceased
      donor kidneys that were preserved by machine pulsatile perfusion at our
      institution between May 1998 and November 2002 using the bleomycin detectable
      iron assay. During machine pulsatile perfusion, redox-active iron was released
      into the preservation solution. Ischemically injured NHB donor kidneys had
      significantly higher perfusate redox-active iron concentrations than heart
      beating (HB) donor kidneys that were not subjected to warm ischemia (3.9 +/- 1.1
      vs. 2.8 +/- 1.0 micromol/L, p = 0.001). Moreover, redox-active iron concentration
      was an independent predictor of post-transplant graft viability (odds ratio 1.68,
      p = 0.01) and added predictive value to currently available donor and graft
      characteristics. This was particularly evident in uncontrolled NHB donor kidneys
      for which there is the greatest uncertainty about transplant outcomes. Therefore,
      perfusate redox-active iron concentration shows promise as a novel viability
      marker of NHB donor kidneys.

PMID- 16889605
TI  - Laparoscopic-assisted right lobe donor hepatectomy.
AB  - The major impediment to a wider application of living donor hepatectomy,
      particularly of the right lobe, is its associated morbidity. The recent interest
      in a minimally invasive approach to liver surgery has raised the possibility of
      applying these techniques to living donor right lobectomy. Herein, we report the
      first case of a laparoscopic, hand-assisted living donor right hepatic lobectomy.
      We describe the technical aspects of the procedure, and discuss the rationale for
      considering this option. We propose that the procedure, as described, did not
      increase the operative risks of the procedure; instead, it decreased potential
      morbidity. We caution that this procedure should only be considered for select
      donors, and that only surgical teams familiar with both living donor hepatectomy
      and laparoscopic liver surgery should entertain this possibility.

PMID- 16889606
TI  - Living donor renal transplantation using alemtuzumab induction and tacrolimus
      monotherapy.
AB  - Alemtuzumab was used as an induction agent in 205 renal transplant recipients
      undergoing 207 living donor renal transplants. All donor kidneys were recovered
      laparoscopically. Postoperatively, patients were treated with tacrolimus
      monotherapy, and immunosuppression was weaned when possible. Forty-seven
      recipients of living donor renal transplants prior to the induction era who
      received conventional triple drug immunosuppression without antibody induction
      served as historic controls. The mean follow-up was 493 days in the alemtuzumab
      group and 2101 days in the historic control group. Actuarial 1-year patient and
      graft survival were 98.6% and 98.1% in the alemtuzumab group, compared to 93.6%
      and 91.5% in the control group, respectively. The incidence of acute cellular
      rejection (ACR) at 1 year was 6.8% in the alemtuzumab group and 17.0% (p < 0.05)
      in the historic control group. Most (81.3%) episodes of ACR in the alemtuzumab
      group were Banff 1 (a or b) and were sensitive to steroid pulses for the
      treatment of rejection. There was no cytomegalovirus disease or infection. The
      incidence of delayed graft function was 0%, and the incidence of posttransplant
      insulin-dependent diabetes mellitus was 0.5%. This study represents the largest
      series to date of live donor renal transplant recipients undergoing alemtuzumab
      induction, and confirms the short-term safety and efficacy of this approach.

PMID- 16889607
TI  - Connective tissue growth factor is a biomarker and mediator of kidney allograft
      fibrosis.
AB  - Chronic allograft nephropathy (CAN) is a leading cause of kidney graft failure
      following transplantation. Its causes are complex and include both immunological
      and nonimmunological factors. Here we have studied the development of CAN in a
      mouse model of kidney transplantation comparing isografts and allografts. Unlike
      the normal histology and normal serum creatinine of the uninephrectomized,
      nonrejecting isografted mice (0.219 +/- 0.024 mg/dL), allografted mice
      demonstrated severe renal dysfunction (mean serum creatinine 0.519 +/- 0.061
      mg/dL; p < 0.005) with progressive inflammation and fibrosis of the kidney. These
      animals also showed an increased expression of connective tissue growth factor
      (CTGF), both systemically and within the graft. CTGF was highly expressed in
      tubuloepithelial cells of allografts, along with alpha-smooth muscle actin, a
      marker of myofibroblasts, and transcriptionally associated with other markers of
      fibrosis. In vitro studies of tubular epithelium indicate that CTGF is capable of
      inducing EMT, independent of TGF-beta. Finally, in human transplant recipients,
      serum and urine CTGF levels are significantly elevated compared to naive
      individuals. Urinary levels correlated with the histological presence of CAN.
      These studies suggest a critical role of CTGF in graft fibrogenesis, for both
      mouse and man. Thus, CTGF has potential as a biomarker of CAN, and also a
      therapeutic target in managing graft fibrosis.

PMID- 16889608
TI  - Limiting financial disincentives in live organ donation: a rational solution to
      the kidney shortage.
AB  - Availability of kidney transplantation is limited by an inadequate supply of
      organs, with no apparent remedy on the immediate horizon and increasing reliance
      on living donors (LDs). While some have advocated financial remuneration to
      stimulate donation, the National Organ Transplant Act (NOTA) of 1984 expressly
      forbids the offer of 'valuable consideration.' However, recent developments
      indicate some fluidity in the definition of valuable consideration while evolving
      international standards highlight deficiencies (particularly regarding long-term
      care and follow-up) in the current American system. Recognizing that substantial
      financial and physical disincentives exist for LDs, we propose a policy change
      that offers the potential to enhance organ availability as well as address
      concerns regarding long-term care. Donors assume much greater risk than is widely
      acknowledged, risk that can be approximated for the purpose of determining
      appropriate compensation. Our proposal offsets donor risk via a package of
      specific benefits (life insurance, health insurance and a small amount of cash)
      to minimize hazard and ensure donor interests are protected after as well as
      before nephrectomy. It will fund medical follow-up and enable data collection so
      that long-term risk can be accurately assessed. The proposal should be cost
      effective with only a small increase in the number of LDs, and the net benefit
      will become greater if removal of disincentives stimulates even further growth.
      As importantly, by directly linking compensation to risk, we believe it preserves
      the essence of kidney donation as a gift, consistent with NOTA and implementable
      in the United States without altering current legal statutes.

PMID- 16889609
TI  - Activation and maturation of alloreactive CD4-independent, CD8 cytolytic T cells.
AB  - The goal of this study was to determine the in vivo conditions that promote
      activation of the (CD4-independent) CD8+ T cell-mediated rejection pathway. We
      have previously noted that hepatocellular but not islet allografts readily
      activate this rejection pathway. In the current study, we utilized these two cell
      transplant models to investigate whether differences in host cell recruitment to
      the graft site, expression of T-cell activation markers by CD8+ graft
      infiltrating cells (GICs), and/or development of delayed-type hypersensitivity
      (DTH) and cytotoxic T lymphocyte cell-mediated effector functions could account
      for the differential transplant outcomes. The collective results demonstrate that
      recruitment of CD8+ T cells to the site of transplant, CD103 or CD69 expression
      on CD8+ GICs, and activation of alloreactive DTH responses are insufficient to
      initiate CD4-independent, CD8-dependent transplant rejection. Instead, rejection
      by alloreactive (CD4-independent) CD8+ T cells correlated with expression of
      CD25, CD154 and CD43 by CD8+ GICs, in vitro alloproliferation by recipient CD8+ T
      cells, and the development of in vivo allospecific cytolytic effector function.
      These results suggest that tissue-derived factors influence the activation and
      maturation of (CD4-independent) CD8+ T cells into cytolytic effectors, which
      correlates with transplant rejection.

PMID- 16889610
TI  - Prednisolone suppresses the function and promotes apoptosis of plasmacytoid
      dendritic cells.
AB  - Organ transplant recipients are highly susceptible to viral infections early
      after transplantation. Plasmacytoid dendritic cells (PDC) play a major role in
      antiviral immunity. Therefore, we determined the numbers of circulating PDC after
      liver transplantation (LTX) and established the effects of immunosuppressive
      drugs on PDC survival and function. PDC were determined longitudinally in 13 LTX
      recipients treated with prednisone and cyclosporin or tacrolimus. Purified PDC
      were cultured with or without clinically relevant concentrations of cyclosporin,
      tacrolimus or prednisolone. Apoptosis induction was monitored by determination of
      active caspase-3, nuclear condensation and annexin-V/7AAD staining. After LTX, a
      4-fold reduction in the number of circulating PDC was observed (p < 0.01), which
      recovered partially after discontinuation of prednisone treatment. In vitro,
      prednisolone induced apoptosis in PDC, while cyclosporin and tacrolimus did not.
      Higher doses of prednisolone were needed to induce apoptosis in Toll-like
      receptor (TLR)-stimulated PDC. However, non-apoptosis inducing concentrations of
      prednisolone suppressed interferon-alpha production, upregulation of co
      stimulatory molecules and allo-stimulatory capacity of TLR-stimulated PDC. In
      conclusion, prednisolone induces apoptosis in PDC, which explains the decline in
      circulating PDC numbers after transplantation. Moreover, prednisolone suppresses
      the functions of TLR-stimulated PDC. Therefore, corticosteroid-free
      immunosuppressive therapy may reduce the number and severity of viral infections
      after transplantation.

PMID- 16889612
TI  - Relationships between the adverse effects of drugs and genetic polymorphism in
      genes encoding drug metabolizing enzymes.

PMID- 16889613
TI  - Statins down under.

PMID- 16889614
TI  - Treatment options in relapsed or refractory Hodgkin disease patients: the mini
      BEAM regimen does exist too.

PMID- 16889616
TI  - Needle-like cryoglobulin crystals presenting as spurious thrombocytosis.

PMID- 16889615
TI  - Significant increase of CKS1B amplification from monoclonal gammopathy of
      undetermined significance to multiple myeloma and plasma cell leukaemia as
      demonstrated by interphase fluorescence in situ hybridisation.
AB  - The genetic events that lead to tumour progression in plasma cell dyscrasia are
      not well understood. Interphase cytoplasmic fluorescence in situ hybridisation
      was used to investigate the CKS1B amplification status (at 1q21) in clonal plasma
      cells from 123 patients: 23 monoclonal gammopathy of undetermined significance
      (MGUS), 75 multiple myeloma (MM) and 26 plasma cell leukaemia (PCL). While CKS1B
      amplification was absent in MGUS patients, such amplification (3-8 copies) was
      detected in 36% of newly diagnosed MM, 52% relapsed MM and 62% PCL (P < 0.001).
      Our results suggest that CKS1B amplification is associated with transformation
      from MGUS to MM and progression to PCL.

PMID- 16889617
TI  - Postradiation mesothelioma: diagnosis on fine needle cytology sample.

PMID- 16889618
TI  - Absolute lymphocyte count predicts overall survival in follicular lymphomas.
AB  - The peripheral blood absolute lymphocyte count (ALC) recovery after autologous
      stem cell transplantation has been shown to be an independent prognostic factor
      for survival for different haematologic malignancies. The role of ALC at
      diagnosis for follicular (grades 1 and 2) lymphomas (FL) on survival is not well
      described. The primary objective of this study was to assess the role of ALC on
      overall survival (OS) in FL patients. Of 1104 FL patients, 228 patients were
      originally diagnosed, followed, and had all treatment at the Mayo Clinic from
      1984 and 1999, were evaluated. The median follow-up was 89 months (range: 8.35
      248). ALC as a continuous variable was identified as a predictor for OS [Hazard
      ratio (HR) = 0.74, P < 0.04]. ALC >/= 1.0 x 10(9)/l (n = 164) predicted a longer
      OS versus ALC < 1.0 x 10(9)/l (n = 64; 175 vs. 73 months respectively, P <
      0.0001). When compared with the Follicular Lymphoma International Prognostic
      Index (FLIPI), ALC was an independent prognostic factor for OS by multivariate
      analysis (HR = 0.677, P < 0.0001). These data suggest a critical role of FL
      patients' immune status at diagnosis on survival.

PMID- 16889619
TI  - Myeloma in monozygotic twin.

PMID- 16889620
TI  - Incidence, risk factors and management of osteonecrosis of the jaw in patients
      with multiple myeloma: a single-centre experience in 303 patients.
AB  - The incidence, characteristics and risk factors for the development of
      osteonecrosis of the jaw (ONJ) were evaluated among 303 myeloma patients. Only
      patients who received bisphosphonates developed ONJ (28/254; 11%). Zoledronic
      acid produced 9.5-fold greater risk for developing ONJ than pamidronate alone (P
      = 0.042) and 4.5-fold greater risk than subsequent use of pamidronate +
      zoledronic acid (P = 0.018). Use of thalidomide and number of bisphosphonate
      infusions also increased the risk for ONJ by 2.4-fold (P = 0.043), and 4.9-fold
      respectively (P = 0.012). ONJ developed earlier among patients receiving
      zoledronic acid. Our data indicates that administration of zoledronic acid for
      more than 2 years or in combination with thalidomide requires caution in myeloma.

PMID- 16889621
TI  - Long-term survival in post-transplant lymphoproliferative disorders with a dose
      adjusted ACVBP regimen.
AB  - Post-transplant lymphoproliferative disorders (PTLD) are severe complications
      after solid organ transplantation with no consensus on best treatment practice.
      Chemotherapy is a therapeutic option with a high response and a significant
      relapse rate leading to a low long-term tolerance rate. Currently, most centres
      use anthracycline-based drug combinations, such as CHOP (cyclophosphamide,
      doxorubicin, vincristine and prednisone). We assessed the efficacy and safety of
      a dose-adjusted ACVBP (doxorubicin reduced to 50 mg/m(2), cyclophosphamide
      adjusted to renal function, vindesine, bleomycin, prednisone) regimen in patients
      failing to respond to a reduction in immunosuppressive therapy. Favourable
      responses were observed in 24 (73%) of the 33 treated patients. Fourteen (42%)
      patients died, mostly from PTLD progression. Actuarial survival was 60% at 5
      years and 55% at 10 years. Survival prognostic factors were: number of involved
      sites (P = 0.007), clinical stage III/IV (P = 0.004), bulky tumour (P < 0.0001),
      B symptoms (P = 0.03), decreased serum albumin (P = 0.03) and poor performance
      status (P = 0.06). Both the international and the PTLD prognostic index were
      predictive for survival (P = 0.001 and P = 0.002, respectively). Overall 128
      cycles were given. Grade 3 or 4 neutropenia was recorded after 26 (20%)
      chemotherapy cycles in 19 (58%) patients. Forty-one (32%) infections were
      recorded in 26 (79%) patients. This study demonstrated that an individual dose
      adjustment of ACVBP regimen was manageable in PTLD patients and favourably
      impacted on long-term survival.

PMID- 16889622
TI  - Co-ordinate action of bacterial adhesins and human carcinoembryonic antigen
      receptors in enhanced cellular invasion by capsulate serum resistant Neisseria
      meningitidis.
AB  - Neisseria meningitidis (Nm) is a human specific opportunistic pathogen that
      occasionally penetrates mucosal barriers via the action of adhesins and invasins
      and evades host immune mechanisms during further dissemination via capsule
      expression. From in vitro studies, the primary adhesion of capsulate bacteria is
      believed to be mediated by polymeric pili, followed by invasion via outer
      membrane adhesins such as Opa proteins. As the latter requires the surface
      capsule to be down-modulated, invading bacteria would be serum sensitive and thus
      avirulent. However, there is recent evidence that capsulate bacteria may interact
      via Opa proteins when host cells express high levels of carcinoembryonic antigen
      related cell adhesion molecules (CEACAMs), their target receptors. Such a
      situation may arise following increased circulation of inflammatory cytokines
      that upregulate certain adhesion molecules on host cells. In this study, using a
      tetracycline controlled expression system, we have developed cell lines with
      inducible CEACAM expression to mimic post-inflammation state of target tissues
      and analysed the interplay between the three surface components capsule, pili and
      Opa proteins in cellular interactions. With two distinct cell lines, not only the
      level but also the rate of adhesion of capsulate Opa-expressing Nm increased
      concurrently with CEACAM density. Moreover, when threshold levels of receptor
      were reached, cellular invasion ensued in an Opa-dependent manner. In studies
      with cell lines intrinsically expressing pilus receptors, notable synergism in
      cellular interactions between pili and Opa of several meningococcal strains was
      observed and was independent of capsule type. A number of internalized bacteria
      were shown to express capsule and when directly isolated from host cells, these
      bacteria were as serum resistant as the inoculated phenotype. Furthermore, we
      observed that agents that block Opa-CEACAM binding substantially reduced cellular
      invasion, while maintaining a low level of cellular adhesion. These studies
      highlight some of the factors that may determine increased host susceptibility to
      infection by serum resistant phenotypes; and demonstrate the potential of
      selective inhibition of key interactions in preventing target tissue penetration
      while maintaining a level of colonization.

PMID- 16889623
TI  - The inhibitory effect of Mycoplasma fermentans on tumour necrosis factor (TNF)
      alpha-induced apoptosis resides in the membrane lipoproteins.
AB  - Mycoplasma have been shown to be involved in the alteration of several eukaryotic
      cell functions, such as cytokine production, gene expression and more. We have
      previously reported that infection of human myelomonocytic U937 cell line with
      live Mycoplasma fermentans (M. fermentans) inhibited tumour necrosis factor (TNF
      alpha)-induced apoptosis. Mycoplasmal membrane lipoproteins are considered to be
      the most potent initiators of inflammatory reactions in mycoplasmal infections.
      The aim of this study was to clarify whether the inhibitory effect on TNFalpha
      induced apoptosis is exerted by M. fermentans lipoproteins (LPMf). A significant
      reduction in TNFalpha-induced apoptosis was demonstrated by stimulation of U937
      cells with M. fermentans total proteins, LPMf or MALP-2 (M. fermentans synthetic
      lipopeptide), but not with M. fermentans hydrophilic protein preparation (AqMf).
      To investigate the mechanism of M. fermentans antiapoptotic effect, the reduction
      of mitochondrial transmembrane potential (delta psi m) was measured. M.
      fermentans total proteins LPMf and MALP-2, but not AqMf, inhibited the reduction
      of delta psi m. In addition, M. fermentans total proteins LPMf and MALP-2, but
      not AqMf, downregulated the formation of active caspase-8. NF-kappaB was
      transactivated in cells treated with M. fermentans lipoproteins, and was
      essential for host cell survival, but not for the inhibition of TNFalpha-induced
      apoptosis by LPMf. Our results suggest that the inhibitory effect exerted by M.
      fermentans on TNFalpha-induced apoptosis in U937 cells is due to the membrane
      lipoproteins of these bacteria.

PMID- 16889624
TI  - Aquaporins contribute to diarrhoea caused by attaching and effacing bacterial
      pathogens.
AB  - Attaching and effacing (A/E) pathogens such as enterohemorrhagic Escherichia coli
      (EHEC) and enteropathogenic E. coli (EPEC) cause serious global health problems.
      These bacteria colonize the gastrointestinal system, attach to intestinal
      epithelial cells, efface (collapse) infected cell microvilli and cause overt
      diarrhoea that may ultimately result in death of the host. Although
      pathogenically induced diarrhoea is a significant global health issue, the
      molecular mechanisms that underlie this disease remain largely unknown. A natural
      murine infection model, employing the A/E pathogen Citrobacter rodentium, has
      been helpful in studying the diseases in vivo. C. rodentium colonize the colon at
      high levels, attach to colonocytes, efface microvilli and cause hyperplasia and
      inflammation in infected mice. As the disease progresses, the mice develop a
      diarrhoea-like phenotype. Aquaporin (AQP) water channels have been proposed to
      play a role in the normal dehydration of faecal contents. Here we examine whether
      C. rodentium infection may alter AQP localization in colonocytes. We demonstrate
      that during infection, AQP2 and AQP3 are mislocalized from their normal location
      along cell membranes to the cell cytoplasm. The change in localization of these
      proteins correlates with the diarrhoea-like phenotype present in infected mice.
      Mice that recover from the infection at 28-35 days post inoculum regain their
      normal membrane AQP localization. The altered localization of AQPs is partially
      dependent on the bacterial type III effector proteins EspF and EspG. We conclude
      that altered AQP localization may be a contributing factor to diarrhoea during
      bacterial infection.

PMID- 16889625
TI  - Pseudomonas aeruginosa ExoS ADP-ribosyltransferase inhibits ERM phosphorylation.
AB  - Pseudomonas aeruginosa causes life-threatening infections in compromised and
      cystic fibrosis patients. Pathogenesis stems from a number of virulence factors,
      including four type III translocated cytotoxins: ExoS, ExoT, ExoY and ExoU. ExoS
      is a bifunctional toxin: the N terminus (amino acids 96-219) encodes a Rho GTPase
      Activating Protein (GAP) domain. The C terminus (amino acids 234-453) encodes a
      14-3-3-dependent ADP-ribosyltransferase domain which transfers ADP-ribose from
      NAD onto substrates such as the Ras GTPases and vimentin. Ezrin/radixin/moesin
      (ERM) proteins have recently been identified as high-affinity substrates for ADP
      ribosylation by ExoS. Expression of ExoS in HeLa cells led to a loss of
      phosphorylation of ERM proteins that was dependent upon the expression of ADP
      ribosyltransferase activity. MALDI-MS and site-directed mutagenesis studies
      determined that ExoS ADP-ribosylated moesin at three C-terminal arginines
      (Arg553, Arg560 and Arg563), which cluster Thr558, the site of phosphorylation by
      protein kinase C and Rho kinase. ADP-ribosylated-moesin was a poor target for
      phosphorylation by protein kinase C and Rho kinase, which showed that ADP
      ribosylation directly inhibited ERM phosphorylation. Expression of dominant
      active-moesin inhibited cell rounding elicited by ExoS, indicating that moesin is
      a physiological target in cultured cells. This is the first demonstration that a
      bacterial toxin inhibits the phosphorylation of a mammalian protein through ADP
      ribosylation. These data explain how the expression of the ADP-ribosylation of
      ExoS modifies the actin cytoskeleton and indicate that ExoS possesses redundant
      enzymatic activities to depolymerize the actin cytoskeleton.

PMID- 16889627
TI  - G-CSF-mediated inhibition of JNK is a key mechanism for Lactobacillus rhamnosus
      induced suppression of TNF production in macrophages.
AB  - Lactobacillus rhamnosus is a human commensal with known immunomodulatory
      properties. To date the mechanism of these immunomodulatory effects is not well
      understood. To unravel the immunomodulatory signalling mechanism, we investigated
      the effects of two strains of L. rhamnosus, L. rhamnosus GG and GR-1, in
      modulating production of tumour necrosis factor-alpha (TNF) in human monocytic
      cell line THP-1 and mouse macrophages. Live L. rhamnosus GG and GR-1 or their
      spent culture supernatant induced minuscule amounts of TNF production but large
      quantities of granulocyte-colony stimulating factor (G-CSF) in macrophages
      compared with those induced by pathogenic Escherichia coli GR-12 and Enterococcus
      faecalis. By using neutralizing antibodies and G-CSF receptor knockout mice, we
      demonstrated that G-CSF secreted from L. rhamnosus GG- and GR-1-exposed
      macrophages suppressed TNF production induced by E. coli- or lipopolysaccharide
      activated macrophages through a paracrine route. The suppression of TNF
      production by G-CSF was mediated through activation of STAT3 and subsequent
      inhibition of c-Jun-N-terminal kinases (JNKs). The inhibition of JNK activation
      required STAT3alpha-mediated de novo protein synthesis. This demonstrates a novel
      role of G-CSF in L. rhamnosus-triggered anti-inflammatory effects and its
      mechanism in the suppression of TNF production in macrophages.

PMID- 16889626
TI  - Leishmania promastigotes activate PI3K/Akt signalling to confer host cell
      resistance to apoptosis.
AB  - Previous reports have shown that cells infected with promastigotes of some
      Leishmania species are resistant to the induction of apoptosis. This would
      suggest that either parasites elaborate factors that block signalling from
      apoptosis inducers or that parasites engage endogenous host signalling pathways
      that block apoptosis. To investigate the latter scenario, we determined whether
      Leishmania infection results in the activation of signalling pathways that have
      been shown to mediate resistance to apoptosis in other infection models. First,
      we showed that infection with the promastigote form of Leishmania major,
      Leishmania pifanoi and Leishmania amazonensis activates signalling through p38
      mitogen-activated protein kinase (MAPK), NFkappaB and PI3K/Akt. Then we found
      that inhibition of signalling through the PI3K/Akt pathway with LY294002 and Akt
      IV inhibitor reversed resistance of infected bone marrow-derived macrophages and
      RAW 264.7 macrophages to potent inducers of apoptosis. Moreover, reduction of Akt
      levels with small interfering RNAs to Akt resulted in the inability of infected
      macrophages to resist apoptosis. Further evidence of the role of PI3K/Akt
      signalling in the promotion of cell survival by infected cells was obtained with
      the finding that Bad, which is a substrate of Akt, becomes phosphorylated during
      the course of infection. In contrast to the observations with PI3K/Akt
      signalling, inhibition of p38 MAPK signalling with SB202190 or NFkappaB
      signalling with wedelolactone had limited effect on parasite-induced resistance
      to apoptosis. We conclude that Leishmania promastigotes engage PI3K/Akt
      signalling, which confers to the infected cell, the capacity to resist death from
      activators of apoptosis.

PMID- 16889628
TI  - Association between passive smoking and salivary markers related to
      periodontitis.
AB  - OBJECTIVES: The mechanism of passive smoking in terms of development of
      periodontitis has not been investigated. This study examined the effect of
      passive smoking on salivary markers related to periodontitis. METHODS:
      Periodontal status was evaluated on the basis of probing pocket depth and
      clinical attachment level in 273 workers. Salivary marker levels were determined
      by enzyme assay including enzyme-linked immunosorbent assay. Six periodontal
      pathogens in saliva were assessed using real-time PCR methodology. Non-, passive
      and active smokers were defined as subjects exhibiting salivary cotinine levels
      of 0 (53 subjects), 1-7 (118) and > or = 8 ng/ml (102). RESULTS: Levels of
      salivary markers, including IL-1beta, lactoferrin, albumin and aspartate
      aminotransferase (AST), were elevated significantly in passive smokers relative
      to non-smokers. Additionally, these marker levels, with the exception of IL
      1beta, decreased significantly in active smokers in comparison with passive
      smokers. However, no meaningful differences in percentages of periodontal
      pathogens were observed between non- and passive smokers. Multiple linear
      regression analyses were performed for each marker utilizing age, gender,
      cotinine level and periodontal status as independent variables. IL-1beta, albumin
      and AST were independently associated with cotinine level. CONCLUSION: Passive
      smoke exposure leads to elevation of IL-1beta, albumin and AST levels in saliva.

PMID- 16889629
TI  - Periodontal healing after non-surgical therapy with a modified sonic scaler: a
      controlled clinical trial.
AB  - AIM: The aim of this study was to compare the clinical and microbiological
      healing outcomes following non-surgical periodontal therapy using a modified
      sonic scaler system versus scaling and root planing (S/RP) with hand instruments.
      MATERIAL AND METHODS: The study comprised 20 chronic periodontitis patients.
      Using a split-mouth design, both treatment modalities were randomly applied to
      one quadrant of the upper and lower jaws. Clinical and microbiological parameters
      were assessed at baseline, 4 weeks, and 6 months after treatment. Furthermore,
      post-operative hypersensitivity was investigated. The Wilcoxon signed-rank test
      (alpha = 0.05) was used for statistical analysis. RESULTS: With both therapy
      methods, periodontal conditions showed statistically significant clinical and
      microbiological improvements after 4 weeks and 6 months. Hypersensitive teeth
      were found only 4 weeks after S/RP. Besides a significantly better bleeding on
      probing reduction in deep S/RP sites and less time required for root
      instrumentation by the sonic scaler, no other clinical and microbiological
      parameters revealed significant differences between sites treated with the sonic
      scaler or S/RP. CONCLUSION: The sonic scaler system and S/RP seem to provide
      similarly favourable periodontal healing results, although in deep pockets S/RP
      appeared to achieve a better resolution of inflammation.

PMID- 16889630
TI  - Pre-term delivery and periodontal disease: a case-control study from Croatia.
AB  - AIM: The aim of this report was to assess the strength and influence of
      periodontitis as a possible risk factor for pre-term birth (PTB) in a cohort of
      81 primiparous Croatian mothers aged 18-39 years. METHODS: PTB cases (n = 17;
      mean age 25 +/- 2.9 years; age range 20-33 years) were defined as spontaneous
      delivery after less than 37 completed weeks of gestation that were followed by
      spontaneous labour or spontaneous rupture of membranes. Controls (full-time
      births) were normal births at or after 37 weeks of gestation (n = 64; mean age 25
      +/- 2.9 years; age range 19-39 years). Information on known risk factors and
      obstetric factors included the current pregnancy history, maternal age at
      delivery, pre-natal care, nutritional status, tobacco use, alcohol use,
      genitourinary infections, vaginosis, gestational age, and birth weight. Full
      mouth periodontal examination was performed on all mothers within 2 days of
      delivery. RESULTS: PTB cases had significantly worse periodontal status than
      controls (p = 0.008). Multivariate logistic regression model, after controlling
      for other risk factors, demonstrated that periodontal disease is a significant
      independent risk factor for PTB, with an adjusted odds ratio of 8.13 for the PTB
      group (95% confidence interval 2.73-45.9). CONCLUSION: Periodontal disease
      represents a strong, independent, and clinically significant risk factor for PTB
      in the studied cohort. There are strong indicators that periodontal therapy
      should form a part of preventive prenatal care in Croatia.

PMID- 16889632
TI  - Critical roles of conserved carboxylic acid residues in pigeon cytosolic NADP+
      dependent malic enzyme.
AB  - Malic enzyme catalyses the reduction of NADP+ to NADPH and the decarboxylation of
      L-malate to pyruvate through a general acid/base mechanism. Previous kinetic and
      structural studies differ in their interpretation of the amino acids responsible
      for the general acid/base mechanism. To resolve this discrepancy, we used site
      directed mutagenesis and kinetic analysis to study four conserved carboxylic
      amino acids. With the D257A mutant, the Km for Mn2+ and the kcat decreased
      relative to those of the wild-type by sevenfold and 28-fold, respectively. With
      the E234A mutant, the Km for Mg2+ and L-malate increased relative to those of the
      wild-type by 87-fold and 49-fold, respectively, and the kcat remained unaltered,
      which suggests that the E234 residue plays a critical role in bivalent metal ion
      binding. The kcat for the D235A and D258A mutants decreased relative to that of
      the wild-type by 7800-fold and 5200-fold, respectively, for the overall reaction,
      by 800-fold and 570-fold, respectively, for the pyruvate reduction partial
      reaction, and by 371-fold and 151-fold, respectively, for the oxaloacetate
      decarboxylation. The activities of the overall reaction and the pyruvate
      reduction partial reaction of the D258A mutant were rescued by the presence of 50
      mM sodium azide. In contrast, small free acids did not have a rescue effect on
      the activities of the E234A, D235A, and D257A mutants. These data suggest that
      D258 may act as a general base to extract the hydrogen of the C2 hydroxy group of
      L-malate with the aid of D235-chelated Mn2+ to polarize the hydroxyl group.

PMID- 16889631
TI  - Fcgamma receptor polymorphisms and periodontal status: a prospective follow-up
      study.
AB  - AIMS: The aims of this study were to assess: (i) the distribution of Fcgamma
      receptor polymorphisms among patients with chronic periodontitis ("cases") and
      control subjects with no/minimal loss of periodontal tissue support in a
      Caucasian population; (ii) whether these polymorphisms can serve as severity
      markers for periodontitis; and (iii) whether they have any bearing on the
      response to periodontal therapy. METHODS: The study sample consisted of 132 cases
      and 73 controls of comparable age and gender. Full-mouth periodontal status was
      assessed. Subgingival plaque (PL) samples and blood samples were obtained and
      analysed with respect to 19 bacterial species and homologous serum immunoglobulin
      G titres. Polymorphisms in the Fcgamma receptor IIa (131R/H) and IIIb (NA1/NA2)
      were assessed by polymerase chain reaction. Patients underwent periodontal
      therapy and were followed up at 4 and 30 months. RESULTS: Neither polymorphism
      showed a skewed distribution among cases and controls. At baseline, periodontitis
      patients with Fcgamma RIIa-H/H131 genotype had more PL and deeper pockets than
      patients in other genotype groups (p < 0.05). Both bacterial levels and antibody
      titres were unrelated to genotype. The longitudinal analysis failed to detect an
      association between genotype and response to periodontal therapy. CONCLUSIONS:
      The present data failed to demonstrate a clinically relevant relationship between
      the Fcgamma receptor IIa (131R/H) or IIIb (NA1/NA2) polymorphism and periodontal
      status.

PMID- 16889633
TI  - Contribution of a central proline in model amphipathic alpha-helical peptides to
      self-association, interaction with phospholipids, and antimicrobial mode of
      action.
AB  - Model amphipathic peptides have been widely used as a tool to determine the
      structural and biological properties that control the interaction of peptides
      with membranes. Here, we have focused on the role of a central Pro in membrane
      active peptides. To determine the role of Pro in structure, antibiotic activity,
      and interaction with phospholipids, we generated a series of model amphipathic
      alpha-helical peptides with different chain lengths and containing or lacking a
      single central Pro. CD studies showed that Pro-free peptides (PFPs) formed stable
      alpha-helical structures even in aqueous buffer through self-association, whereas
      Pro-containing peptides (PCPs) had random coil structures. In contrast, in
      trifluoroethanol or SDS micelles, both PFPs and PCPs adopted highly ordered alpha
      helical structures, although relatively lower helical contents were observed for
      the PCPs than the PFPs. This structural consequence indicates that a central Pro
      residue limits the formation of highly helical aggregates in aqueous buffer and
      causes a partial distortion of the stable alpha-helix in membrane-mimetic
      environments. With regard to antibiotic activity, PCPs had a 2-8-fold higher
      antibacterial activity and significantly reduced hemolytic activity compared with
      PFPs. In membrane depolarization assays, PCPs passed rapidly across the
      peptidoglycan layer and immediately dissipated the membrane potential in
      Staphylococcus aureus, whereas PFPs had a greatly reduced ability. Fluorescence
      studies indicated that, although PFPs had strong binding affinity for both
      zwitterionic and anionic liposomes, PCPs interacted weakly with zwitterionic
      liposomes and strongly with anionic liposomes. The selective membrane interaction
      of PCPs with negatively charged phospholipids may explain their antibacterial
      selectivity. The difference in mode of action between PCPs and PFPs was further
      supported by kinetic analysis of surface plasmon resonance data. The possible
      role of the increased local backbone distortion or flexibility introduced by the
      proline residue in the antimicrobial mode of action is discussed.

PMID- 16889634
TI  - Inhibitory properties and solution structure of a potent Bowman-Birk protease
      inhibitor from lentil (Lens culinaris, L) seeds.
AB  - Bowman-Birk serine protease inhibitors are a family of small plant proteins,
      whose physiological role has not been ascertained as yet, while chemopreventive
      anticarcinogenic properties have repeatedly been claimed. In this work we present
      data on the isolation of a lentil (Lens culinaris, L., var. Macrosperma) seed
      trypsin inhibitor (LCTI) and its functional and structural characterization. LCTI
      is a 7448 Da double-headed trypsin/chymotrypsin inhibitor with dissociation
      constants equal to 0.54 nM and 7.25 nM for the two proteases, respectively. The
      inhibitor is, however, hydrolysed by trypsin in a few minutes timescale, leading
      to a dramatic loss of its affinity for the enzyme. This is due to a substantial
      difference in the kon and k*on values (1.1 microM-1.s-1 vs. 0.002 microM-1.s-1),
      respectively, for the intact and modified inhibitor. A similar behaviour was not
      observed with chymotrypsin. The twenty best NMR structures concurrently showed a
      canonical Bowman-Birk inhibitor (BBI) conformation with two antipodal beta
      hairpins containing the inhibitory domains. The tertiary structure is stabilized
      by ion pairs and hydrogen bonds involving the side chain and backbone of Asp10
      Asp26-Arg28 and Asp36-Asp52 residues. At physiological pH, the final structure
      results in an asymmetric distribution of opposite charges with a negative
      electrostatic potential, centred on the C-terminus, and a highly positive
      potential, surrounding the antitryptic domain. The segment 53-55 lacks the
      anchoring capacity found in analogous BBIs, thus rendering the protein
      susceptible to hydrolysis. The inhibitory properties of LCTI, related to the
      simultaneous presence of two key amino acids (Gln18 and His54), render the
      molecule unusual within the natural Bowman-Birk inhibitor family.

PMID- 16889635
TI  - Promoters of type I interferon genes from Atlantic salmon contain two main
      regulatory regions.
AB  - Recognition of viral nucleic acids by vertebrate host cells results in the
      synthesis and secretion of type I interferons (IFN-alpha/beta), which induce an
      antiviral state in neighboring cells. We have cloned the genes and promoters of
      two type I IFNs from Atlantic salmon. Both genes have the potential to encode IFN
      transcripts with either a short or a long 5'-untranslated region, apparently
      controlled by two distinct promoter regions, PR-I and PR-II, respectively. PR-I
      is located within 116 nucleotides upstream of the short transcript and contains a
      TATA-box, two interferon regulatory factor (IRF)-binding motifs, and a putative
      nuclear factor kappa B (NFkappaB)-binding motif. PR-II is located 469-677
      nucleotides upstream of the short transcript and contains three or four IRF
      binding motifs and a putative ATF-2/c-Jun element. Complete and truncated
      versions of the promoters were cloned in front of a luciferase reporter gene and
      analyzed for promoter activity in salmonid cells. Constructs containing PR-I were
      highly induced after treatment with the dsRNA poly(I:C), and promoter activity
      appeared to be dependent on NFkappaB. In contrast, constructs containing
      exclusively PR-II showed poor poly(I:C)-inducible activity. PR-I is thus the main
      control region for IFN-alpha/beta synthesis in salmon. Two pathogenic RNA
      viruses, infectious pancreatic necrosis virus and infectious salmon anemia virus,
      were tested for their ability to stimulate the minimal PR-I, but only the latter
      was able to induce promoter activity. The established IFN promoter-luciferase
      assay will be useful in studies of host-virus interactions in Atlantic salmon, as
      many viruses are known to encode proteins that prevent IFN synthesis by
      inhibition of promoter activation.

PMID- 16889636
TI  - Critical steps in fluoroquinolones and carbapenems prescriptions: results from a
      prospective clinical audit.
AB  - Antibiotic misuse is associated with emergence of resistance and high
      expenditures. Fluoroquinolones (FQ) and carbapenems (CP) are drugs with
      considerable potential of resistance development and its disseminated use is a
      concern. We undertook a prospective clinical audit to evaluate prescriptions of
      FQ and CP in a multistep process. Each prescription was unfolded in the following
      steps: indication for antimicrobial therapy; adequacy of initial prescription,
      dosage and route; previous cultures; and parenteral-oral transition. There was no
      antibiotics indication in 8.9% of FQ and 1.5% of CP group (p = 0.07). In CP 25.8%
      of initial schemes were inappropriate (21% in FQ). Lack of switch to oral therapy
      comprised 25% of monthly costs of FQ. Inadequacy in initial choice accounted for
      13.6% of CP expenses. We concluded that, in spite of infection control
      restrictive policies, inappropriateness of antibiotic usage is worrisome.
      Clinical audit in a multistep approach may identify possible flaws in this
      process.

PMID- 16889637
TI  - A need for a simplified approach to venous thromboembolism prophylaxis in acute
      medical inpatients.
AB  - Venous thromboembolism (VTE) is a major cause of morbidity and mortality in the
      UK. Studies have shown that pulmonary embolism causes or contributes to
      approximately 1 in 10 hospital deaths of medical patients admitted to general
      hospitals in the UK (Lindblad B, Sternby NH, Bergqvist D. BMJ 1991; 302: 709-11),
      with pulmonary embolus being the most common preventable cause of hospital death.
      Thromboprophylaxis is safe, highly effective and cost effective, but despite
      various current clinical guidelines, physicians fail to prescribe prophylaxis for
      the majority of medical inpatients at risk of VTE. This article outlines the
      current evidence for VTE prophylaxis in medical patients and discusses the
      reasons behind the insufficient use of prophylaxis in the acute medical setting.

PMID- 16889638
TI  - Hashimoto's thyroiditis associated with idiopathic retroperitoneal fibrosis: case
      report and review of the literature.
AB  - Idiopathic retroperitoneal fibrosis (IRF) is a rare disease of unknown origin,
      characterised by an inflammatory proliferative fibrosing process occurring in the
      retroperitoneum. Hashimoto's thyroiditis (HT) is a form of chronic thyroiditis
      that in some cases shows an extensive replacement of thyroid parenchyma by
      fibrous tissue. We report the rare association of IRF with HT in a 68-year-old
      woman presenting with pulmonary oedema, acute renal failure due to bilateral
      hydronephrosis and a firm diffuse goitre with hypothyroidism. The so far reported
      cases of IRF associated with chronic thyroiditis are reviewed, and the possible
      aetiopathogenetic link between these two entities is discussed.

PMID- 16889639
TI  - Comparison of intravenous methylprednisolone therapy vs. oral methylprednisolone
      therapy in patients with Graves' ophthalmopathy.
AB  - A prospective, randomised and single blind clinical trial was designed to compare
      intravenous methylprednisolone pulse (IVGC) with oral methylprednisolone (OGC)
      monotherapy in terms of effectiveness and tolerability in Graves' ophthalmopathy
      (GO). Fifty-two consecutive patients with untreated, moderately severe and active
      GO were randomly treated with either IVGC or OGC therapy for 12 weeks. IVGC
      therapy achieved a more rapid and significant improvement than OGC therapy
      according to clinical activity score (p < 0.01), proptosis (p < 0.038), lid width
      (p < 0.0001), extraocular muscle changes (p < 0.02), optic neuropathy. (p <
      0.001), intraocular pressure (p < 0.04), visual acuity (p < 0.03), quality of
      life (p < 0.0001) and treatment response (p < 0.001). Diplopia was significantly
      improved in two groups but there was no difference between them (p < 0.6). Heavy
      smokers indicated alteration of ophthalmic signs with increased thyroid
      stimulating hormone (TSH)-receptor antibody during the therapy. In conclusion,
      IVGC therapy was more effective and better tolerated than OGC therapy in the
      management of GO.

PMID- 16889640
TI  - Characterization of chicken epidermal dendritic cells.
AB  - It has been known for 15 years that the chicken epidermis contains ATPase+ and
      major histocompatibility complex class II-positive (MHCII+) dendritic cells.
      These cells were designated as Langerhans cells but neither their detailed
      phenotype nor their function was further investigated. In the present paper we
      demonstrate a complete overlapping of ATPase, CD45 and vimentin staining in all
      dendritic cells of the chicken epidermis. The CD45+ ATPase+ vimentin+ dendritic
      cells could be divided into three subpopulations: an MHCII+ CD3- KUL01+ and 68.1+
      (monocyte-macrophage subpopulation markers) subpopulation, an MHCII- CD3- KUL01-
      and 68.1- subpopulation and an MHCII- CD3+ KUL01- and 68.1- subpopulation. The
      first population could be designated as chicken Langerhans cells. The last
      population represents CD4- CD8- T-cell receptor-alphabeta- and -gammadelta-
      natural killer cells with cytoplasmic CD3 positivity. The epidermal dendritic
      cells have a low proliferation rate as assessed by bromodeoxyuridine
      incorporation. Both in vivo and in vitro experiments showed that dendritic cells
      could be mobilized from the epidermis. Hapten treatment of epidermis resulted in
      the decrease of the frequency of epidermal dendritic cells and hapten-loaded
      dendritic cells appeared in the dermis or in in vitro culture of isolated
      epidermis. Hapten-positive cells were also found in the so-called dermal lymphoid
      nodules. We suggest that these dermal nodules are responsible for some regional
      immunological functions similar to the mammalian lymph nodes.

PMID- 16889641
TI  - A rapid exocytosis mode in chromaffin cells with a neuronal phenotype.
AB  - We have used astrocyte-conditioned medium (ACM) to promote the
      transdifferentiation of bovine chromaffin cells and study modifications in the
      exocytotic process when these cells acquire a neuronal phenotype. In the ACM
      promoted neuronal phenotype, secretory vesicles and intracellular Ca2+ rise were
      preferentially distributed in the neurite terminals. Using amperometry, we
      observed that the exocytotic events also occurred mainly in the neurite
      terminals, wherein the individual exocytotic events had smaller quantal size than
      in undifferentiated cells. Additionally, duration of pre-spike current was
      significantly shorter, suggesting that ACM also modifies the fusion pore
      stability. After long exposure (7-9 days) to ACM, the kinetics of catecholamine
      release from individual vesicles was markedly accelerated. The morphometric
      analysis of vesicle diameters suggests that the rapid exocytotic events observed
      in neurites of ACM-treated cells correspond to the exocytosis of large dense-core
      vesicles (LDCV). On the other hand, experiments performed in EGTA-loaded cells
      suggest that ACM treatment promotes a better coupling between voltage-gated
      calcium channels (VGCC) and LDCV. Thus, our findings reveal that ACM promotes a
      neuronal phenotype in chromaffin cells, wherein the exocytotic kinetics is
      accelerated. Such rapid exocytosis mode could be caused at least in part by a
      better coupling between secretory vesicles and VGCC.

PMID- 16889642
TI  - Ammonia permeability of the aquaglyceroporins from Plasmodium falciparum,
      Toxoplasma gondii and Trypansoma brucei.
AB  - Plasmodium falciparum uses amino acids from haemoglobin degradation mainly for
      protein biosynthesis. Glutamine, however, is mostly oxidized to 2-oxoglutarate to
      restore NAD(P)H + H+. In this process two molecules of ammonia are released. We
      determined an ammonia production of 9 mmol h(-1) per litre of infected red blood
      cells in the early trophozoite stage. External application of ammonia yielded a
      cytotoxic IC50 concentration of 2.8 mM. As plasmodia cannot metabolize ammonia it
      must be exported. Yet, no biochemical or genomic evidences exist that plasmodia
      possess classical ammonium transporters. We expressed the P. falciparum
      aquaglyceroporin (PfAQP) in Xenopus laevis oocytes and examined whether it may
      serve as an exit pathway for ammonia. We show that injected oocytes: (i) acidify
      the medium due to ammonia uptake, (ii) take up [14C]methylamine and
      [14C]formamide, (iii) swell in solution with formamide and acetamide and (iv)
      display an ammonia-induced NH4+-dependent clamp current. Further, a yeast strain
      lacking the endogenous aquaglyceroporin (Fps1) is rescued by expression of PfAQP
      which provides for the efflux of toxic methylamine. Ammonia permeability was
      similarly established for the aquaglyceroporins from Toxoplasma gondii and
      Trypanosoma brucei. Apparently, these aquaglyceroporins are important for the
      release of ammonia derived from amino acid breakdown.

PMID- 16889643
TI  - Ferri-bacillibactin uptake and hydrolysis in Bacillus subtilis.
AB  - Upon iron limitation, Bacillus subtilis secretes the catecholic trilactone (2,3
      dihydroxybenzoate-glycine-threonine)3 siderophore bacillibactin (BB) for ferric
      iron scavenging. Here, we show that ferri-BB uptake is mediated by the FeuABC
      transporter and that YuiI, a novel trilactone hydrolase, catalyses ferri-BB
      hydrolysis leading to cytosolic iron release. Among several Fur-regulated ABC
      transport mutants, only DeltafeuABC exhibited impaired growth during iron
      starvation. Quantification of intra- and extracellular (ferri)-BB in iron
      depleted DeltafeuABC cultures revealed a fourfold increase of the extracellular
      siderophore concentration, confirming a blocked ferri-BB uptake in the absence of
      FeuABC. Ferri-BB was found to bind selectively to the periplasmic binding protein
      FeuA (Kd = 57 +/- 1 nM), proving high-affinity transport of the iron-charged
      siderophore. During iron starvation, a DeltayuiI mutant displayed impaired growth
      and strong intracellular (30-fold) and extracellular (6.5-fold) (ferri)-BB
      accumulation. Kinetic studies in vitro revealed that YuiI hydrolyses both BB and
      ferri-BB. While BB hydrolysis led to strong accumulation of the tri- and dimeric
      reaction intermediates, ferri-BB hydrolysis yielded exclusively the monomeric
      reaction product and occurred with a 25-fold higher catalytic efficiency than BB
      single hydrolysis. Thus, ferri-BB was the preferred substrate of the YuiI
      esterase whose gene locus was designated besA.

PMID- 16889644
TI  - Co-regulation of motility, exoenzyme and antibiotic production by the EnvZ-OmpR
      FlhDC-FliA pathway in Xenorhabdus nematophila.
AB  - Xenorhabdus nematophila is an emerging model for both mutualism and pathogenicity
      in different invertebrate hosts. Here we conduct a mutant study of the EnvZ-OmpR
      two-component system and the flagella sigma factor, FliA (sigma28). Both ompR and
      envZ strains displayed precocious swarming behaviour, elevated flhD and fliA mRNA
      levels and early production of lipase, protease, haemolysin and antibiotic
      activity. Inactivation of fliA eliminated exoenzyme production which was restored
      by complementation with the fliAZ operon. Inactivation of flhA, a gene encoding a
      component of the flagella export apparatus, eliminated lipase but not protease or
      haemolysin production indicating these enzymes are secreted by different export
      pathways. FliA-regulated lipase (xlpA) and protease (xrtA) genes were identified.
      Their expression and level of production were elevated in the ompR and envZ
      strains and markedly reduced in the fliA strain while both were expressed
      normally in the flhA strain. We also found that expression of nrps1 which encodes
      a non-ribosomal peptide synthetase was elevated in the ompR and envZ strains. The
      fliA strain was pathogenic towards the insect host indicating that motility and
      FliA-regulated exoenzyme production were not essential for virulence. These
      findings support a model in which the EnvZ-OmpR-FlhDC-FliA regulatory network co
      ordinately controls flagella synthesis, and exoenzyme and antibiotic production
      in X. nematophila.

PMID- 16889646
TI  - SERRATE is a novel nuclear regulator in primary microRNA processing in
      Arabidopsis.
AB  - The Arabidopsis gene SERRATE (SE) controls leaf development, meristem activity,
      inflorescence architecture and developmental phase transition. It has been
      suggested that SE, which encodes a C(2)H(2) zinc finger protein, may change gene
      expression via chromatin modification. Recently, SE has also been shown to
      regulate specific microRNAs (miRNAs), miR165/166, and thus control shoot meristem
      function and leaf polarity. However, it remains unclear whether and how SE
      modulates specific miRNA processing. Here we show that the se mutant exhibits
      some similar developmental abnormalities as the hyponastic leaves1 (hyl1) mutant.
      Since HYL1 is a nuclear double-stranded RNA-binding protein acting in the DICER
      LIKE1 (DCL1) complex to regulate the first step of primary miRNA transcript (pri
      miRNA) processing, we hypothesized that SE could play a previously unrecognized
      and general role in miRNA processing. Genetic analysis supports that SE and HYL1
      act in the same pathway to regulate plant development. Consistently, SE is
      critical for the accumulation of multiple miRNAs and the trans-acting small
      interfering RNA (ta-siRNA), but is not required for sense post-transcriptional
      gene silencing. We further demonstrate that SE is localized in the nucleus and
      interacts physically with HYL1. Finally, we provide evidence that SE and HYL1
      probably act with DCL1 in processing pri-miRNAs before HEN1 in miRNA biogenesis.
      In plants and animals, miRNAs are known to be processed in a stepwise manner from
      pri-miRNA. Our data strongly suggest that SE plays an important and general role
      in pri-miRNA processing, and it would be interesting to determine whether animal
      SE homologues may play similar roles in vivo.

PMID- 16889645
TI  - Peroxidase-dependent apoplastic oxidative burst in Arabidopsis required for
      pathogen resistance.
AB  - The oxidative burst is an early response to pathogen attack leading to the
      production of reactive oxygen species (ROS) including hydrogen peroxide. Two
      major mechanisms involving either NADPH oxidases or peroxidases that may exist
      singly or in combination in different plant species have been proposed for the
      generation of ROS. We identified an Arabidopsis thaliana azide-sensitive but
      diphenylene iodonium-insensitive apoplastic oxidative burst that generates
      H(2)O(2) in response to a Fusarium oxysporum cell-wall preparation. Transgenic
      Arabidopsis plants expressing an anti-sense cDNA encoding a type III peroxidase,
      French bean peroxidase type 1 (FBP1) exhibited an impaired oxidative burst and
      were more susceptible than wild-type plants to both fungal and bacterial
      pathogens. Transcriptional profiling and RT-PCR analysis showed that the anti
      sense (FBP1) transgenic plants had reduced levels of specific peroxidase-encoding
      mRNAs, including mRNAs corresponding to Arabidopsis genes At3g49120 (AtPCb) and
      At3g49110 (AtPCa) that encode two class III peroxidases with a high degree of
      homology to FBP1. These data indicate that peroxidases play a significant role in
      generating H(2)O(2) during the Arabidopsis defense response and in conferring
      resistance to a wide range of pathogens.

PMID- 16889647
TI  - The Arabidopsis thaliana TIR-NB-LRR R-protein, RPP1A; protein localization and
      constitutive activation of defence by truncated alleles in tobacco and
      Arabidopsis.
AB  - Specific recognition of Hyaloperonospora parasitica isolate Cala2 by Arabidopsis
      thaliana Ws-0 is mediated by the resistance gene RPP1A. Transient expression of
      different truncations of RPP1A in tobacco leaves revealed that its TIR-NB-ARC
      portion is sufficient to induce an elicitor-independent cell death. In stable
      transgenic lines of Arabidopsis, overexpression of the RPP1A TIR-NB-ARC domains
      (E12) using the 35S promoter leads to broad-spectrum resistance to virulent
      strains of H. parasitica and Pseudomonas syringae DC3000. The TIR-NB-ARC-mediated
      constitutive immunity is due to activation of the salicylic acid-dependent
      resistance pathway and is relieved by either a mutation in EDS1 or the presence
      of the salicylate hydroxylase gene, NahG. Growth of 35S::E12 plants is reduced, a
      phenotype observed in many constitutively resistant mutants. RPP1A carries a
      hydrophobic peptide at its N-terminus that directs the RPP1A protein into
      membranes, though it may not be the sole determinant mediating membrane
      association of RPP1A. Two-phase partitioning and sucrose density gradient
      sedimentation established that RPP1A resides in the endoplasmic reticulum and/or
      Golgi apparatus.

PMID- 16889648
TI  - Mutation of SAD2, an importin beta-domain protein in Arabidopsis, alters abscisic
      acid sensitivity.
AB  - A number of protein and RNA-processing mutants have been shown to affect ABA
      sensitivity. A new mutant, sad2-1, was isolated from a T-DNA mutagenized
      population of RD29A:LUC plants and shown to have increased luminescence after
      ABA, salt, cold or polyethylene glycol treatments. Expression of several ABA- and
      stress-responsive genes was higher in the mutant than in the wild type. sad2-1
      also exhibited ABA hypersensitivity in seed germination and seedling growth. SAD2
      was found to encode an importin beta-domain family protein likely to be involved
      in nuclear transport. SAD2 was expressed at a low level in all tissues examined
      except flowers, but SAD2 expression was not inducible by ABA or stress.
      Subcellular localization of GFP-tagged SAD2 showed a predominantly nuclear
      localization, consistent with a role for SAD2 in nuclear transport. Knockout of
      the closest importin beta homolog of SAD2 in Arabidopsis did not duplicate the
      sad2 phenotype, indicating that SAD2 plays a specific role in ABA signaling.
      Analysis of RD29A:LUC luminescence and ABA and stress sensitivity in double
      mutants of sad2-1 and sad1 or abh1-7, a newly isolated allele of ABH1 also in the
      RD29A:LUC background, suggested that SAD2 acts upstream of or has additive
      effects with these two genes. The results suggest a role for nuclear transport in
      ABA signal transduction, and the possible roles of SAD2 in relation to that of
      SAD1 and ABH1 are discussed.

PMID- 16889649
TI  - Mapped Ds/T-DNA launch pads for functional genomics in barley.
AB  - A system for targeted gene tagging and local saturation mutagenesis based on
      maize transposable elements (Ac/Ds) was developed in barley (Hordeum vulgare L.).
      We generated large numbers of transgenic barley lines carrying a single copy of
      the non-autonomous maize Ds element at defined positions in the genome.
      Independent Ds lines were either generated by activating Ds elements in existing
      single-copy lines after crossing with AcTPase-expressing plants or by
      Agrobacterium-mediated transformation. Genomic DNA flanking Ds and T-DNA
      insertion sites from over 200 independent lines was isolated and sequenced, and
      was used for a sequence based mapping strategy in a barley reference population.
      More than 100 independent Ds insertion sites were mapped and can be used as
      launch pads for future targeted tagging of genes in the vicinity of the insertion
      sites. Sequence analysis of Ds and T-DNA flanking regions revealed a sevenfold
      preference of both mutagens for insertion into non-redundant, gene-containing
      regions of the barley genome. However, whilst transposed Ds elements
      preferentially inserted adjacent to regions with a high number of predicted and
      experimentally validated matrix attachment regions (nuclear MARs), this was not
      the case for T-DNA integration sites. These findings and an observed high
      transposition frequency from mapped launch pads demonstrate the future potential
      of gene tagging for functional genomics and gene discovery in barley.

PMID- 16889652
TI  - Fast and precise protein tracking using repeated reversible photoactivation.
AB  - Photoactivatable fluorescent proteins opened principally novel possibilities to
      study proteins' movement pathways. In particular, reversibly photoactivatable
      proteins enable multiple tracking experiments in a long-drawn work with a single
      cell. Here we report 'protein rivers tracking' technique based on repeated
      identical rounds of photoactivation and subsequent images averaging, which
      results in dramatic increase of imaging resolution for fast protein movement
      events.

PMID- 16889651
TI  - The phs1-3 mutation in a putative dual-specificity protein tyrosine phosphatase
      gene provokes hypersensitive responses to abscisic acid in Arabidopsis thaliana.
AB  - The plant hormone abscisic acid (ABA) controls numerous physiological traits:
      dormancy and germination of seeds, senescence and resistance to abiotic stresses.
      In order to get more insight into the role of protein tyrosine phosphatase (PTP)
      in ABA signalling, we obtained eight homozygous T-DNA insertion lines in
      Arabidopsis thaliana PTP genes. One mutant, named phs1-3, exhibited a strong ABA
      induced inhibition of germination as only 26% of its seeds germinated after 3
      days instead of 92% for the Columbia (Col-0) line. Genetic and molecular analyses
      of phs1-3 showed that it bears a unique T-DNA insertion in the promoter of the
      gene and that the mutation is recessive. PHS1 expression in the mutant is about
      half that of the Col-0 line. The upregulation of two ABA-induced genes
      (At5g06760, RAB18) and the downregulation of two ABA-repressed genes (AtCLC-A,
      ACL) are enhanced in the phs1-3 mutant compared with the wild-type. The 'in
      planta' aperture of phs1-3 stomata is reduced and the inhibition of the light
      induced opening of stomata by ABA is stronger in phs1-3 leaves than in Col-0
      leaves. Finally, PHS1 expression is upregulated in the presence of ABA in both
      phs1-3 and Col-0 but more intensively in the mutant. Thus, phs1-3 is
      hypersensitive to ABA. Taken together, these results show that PHS1, which
      encodes a dual-specificity PTP, is a negative regulator of ABA signalling.

PMID- 16889650
TI  - Accumulation of genome-specific transcripts, transcription factors and
      phytohormonal regulators during early stages of fiber cell development in
      allotetraploid cotton.
AB  - Gene expression during the early stages of fiber cell development and in
      allopolyploid crops is poorly understood. Here we report computational and
      expression analyses of 32 789 high-quality ESTs derived from Gossypium hirsutum
      L. Texas Marker-1 (TM-1) immature ovules (GH_TMO). The ESTs were assembled into
      8540 unique sequences including 4036 tentative consensus sequences (TCs) and 4504
      singletons, representing approximately 15% of the unique sequences in the cotton
      EST collection. Compared with approximately 178 000 existing ESTs derived from
      elongating fibers and non-fiber tissues, GH_TMO ESTs showed a significant
      increase in the percentage of genes encoding putative transcription factors such
      as MYB and WRKY and genes encoding predicted proteins involved in auxin,
      brassinosteroid (BR), gibberellic acid (GA), abscisic acid (ABA) and ethylene
      signaling pathways. Cotton homologs related to MIXTA, MYB5, GL2 and eight genes
      in the auxin, BR, GA and ethylene pathways were induced during fiber cell
      initiation but repressed in the naked seed mutant (N1N1) that is impaired in
      fiber formation. The data agree with the known roles of MYB and WRKY
      transcription factors in Arabidopsis leaf trichome development and the well
      documented phytohormonal effects on fiber cell development in immature cotton
      ovules cultured in vitro. Moreover, the phytohormonal pathway-related genes were
      induced prior to the activation of MYB-like genes, suggesting an important role
      of phytohormones in cell fate determination. Significantly, AA sub-genome ESTs of
      all functional classifications including cell-cycle control and transcription
      factor activity were selectively enriched in G. hirsutum L., an allotetraploid
      derived from polyploidization between AA and DD genome species, a result
      consistent with the production of long lint fibers in AA genome species. These
      results suggest general roles for genome-specific, phytohormonal and
      transcriptional gene regulation during the early stages of fiber cell development
      in cotton allopolyploids.

PMID- 16889656
TI  - Hospice utilization during the SARS outbreak in Taiwan.
AB  - BACKGROUND: The severe acute respiratory syndrome (SARS) epidemic threw the world
      into turmoil during the first half of 2003. Many subsequent papers have addressed
      its impact on health service utilization, but few have considered palliative
      (hospice) care. The aim of the present study was to describe changes in hospice
      inpatient utilization during and after the SARS epidemic in 2003 in Taiwan.
      METHODS: The data sources were the complete datasets of inpatient admissions
      during 2002 and 2003 from the National Health Insurance Research Database. Before
      and-after comparisons of daily and monthly utilizations were made. Hospice
      analyses were limited to those wards that offered inpatient services throughout
      these two years. The comparisons were extended to total hospital bed utilization
      and to patients who were still admitted to hospice wards during the peak period
      of the SARS epidemic. RESULTS: Only 15 hospice wards operated throughout the
      whole of 2002 and 2003. In 2003, hospice utilization began to decrease in the
      middle of April, reached a minimum on 25 May, and gradually recovered to the
      level of the previous November. Hospices showed a more marked reduction in
      utilization than all hospital beds (e.g. -52.5% vs. -19.9% in May 2003) and a
      slower recovery with a three-month lag. In total, 566 patients were admitted to
      hospice wards in May/June 2003, in contrast to 818 in May/June 2002. Gender, age
      and diagnosis distributions did not differ. CONCLUSION: Hospice inpatient
      utilization in Taiwan was indeed more sensitive to the emerging epidemic than
      general inpatient utilization. A well-balanced network with seamless continuity
      of care should be ensured.

PMID- 16889657
TI  - Participants' perceptions of a lifestyle approach to promoting physical activity:
      targeting deprived communities in Kingston-upon-Hull.
AB  - BACKGROUND: The health benefits of an active lifestyle have been extensively
      documented and generally accepted. In the UK, declining physical activity levels
      are a major contributing factor to a number of public health concerns such as
      obesity and coronary heart disease. Clearly, there is an urgent need to support
      people in developing sustainable active lifestyles. In 2003, a new lifestyle
      based physical activity service called Active Lifestyles (AL) was set up in
      Kingston-upon-Hull to help local residents to become more active and develop
      healthier lifestyles. The service targeted the most deprived communities in the
      city. The aim of the study was to explore participants' perceptions of the
      operation and effectiveness of the AL service. METHODS: Five focus groups were
      conducted in community centres and offices in the health promotion service in
      Kingston-upon-Hull. Sixteen white adult males (n = 5) and females (n = 11)
      participated in the study. Ages ranged from 15-73 years (mean age = 53 years).
      Data were analysed using a content analysis technique based on the 'framework'
      approach. RESULTS: Three broad themes emerged from the focus groups; the referral
      process; operational aspects of the AL service; and perceived benefits of the
      service. Overall, participants were extremely positive about the AL service. Many
      reported increased activity levels, modified eating habits, and enhanced
      awareness and education regarding healthier living. Most participants reported
      that local awareness of the AL service was low and greater promotion was required
      so more people could benefit. The success of the service was highly dependent
      upon the qualities and approach of the AL advisor. CONCLUSION: The service
      appears to have filled a gap in service provision since it offered support to the
      most sedentary, older, unfit and overweight individuals, many of whom live in the
      most deprived parts of Kingston-upon-Hull. Traditional exercise referral schemes
      that focus solely on facility-based exercise should be broadened to encompass
      everyday lifestyle activity, where referral to a gym or exercise facility is just
      one of a number of physical activity options.

PMID- 16889658
TI  - Similar support for three different life course socioeconomic models on
      predicting premature cardiovascular mortality and all-cause mortality.
AB  - BACKGROUND: There are at least three broad conceptual models for the impact of
      the social environment on adult disease: the critical period, social mobility,
      and cumulative life course models. Several studies have shown an association
      between each of these models and mortality. However, few studies have
      investigated the importance of the different models within the same setting and
      none has been performed in samples of the whole population. The purpose of the
      present study was to study the relation between socioeconomic position (SEP) and
      mortality using different conceptual models in the whole population of Scania.
      METHODS: In the present investigation we use socioeconomic information on all men
      (N = 48,909) and women (N = 47,688) born between 1945 and 1950, alive on January,
      1st,1990, and living in the Region of Scania, in Sweden. Focusing on three
      specific life periods (i.e., ages 10-15, 30-35 and 40-45), we examined the
      association between SEP and the 12-year risk of premature cardiovascular
      mortality and all-cause mortality. RESULTS: There was a strong relation between
      SEP and mortality among those inside the workforce, irrespective of the
      conceptual model used. There was a clear upward trend in the mortality hazard
      rate ratios (HRR) with accumulated exposure to manual SEP in both men (p for
      trend < 0.001 for both cardiovascular and all-cause mortality) and women (p for
      trend = 0.01 for cardiovascular mortality) and (p for trend = 0.003 for all-cause
      mortality). Inter- and intragenerational downward social mobility was associated
      with an increased mortality risk. When applying similar conceptual models based
      on workforce participation, it was shown that mortality was affected by the
      accumulated exposure to being outside the workforce. CONCLUSION: There was a
      strong relation between SEP and cardiovascular and all-cause mortality,
      irrespective of the conceptual model used. The critical period, social mobility,
      and cumulative life course models, showed the same fit to the data. That is, one
      model could not be pointed out as "the best" model and even in this large
      unselected sample it was not possible to adjudicate which theories best describe
      the links between life course SEP and mortality risk.

PMID- 16889660
TI  - Smoking marijuana in public: the spatial and policy shift in New York City
      arrests, 1992-2003.
AB  - BACKGROUND: During the 1990s, the New York Police Department (NYPD) greatly
      expanded arrests for smoking marijuana in public view (MPV). By 2000, MPV
      accounted for 15% of all arrests. The NYPD's supporters report this arrest
      activity is just part of quality-of-life (QOL) policing, which seeks to promote
      order in public locations by aggressively patrolling for behaviors that offend
      the general population. The NYPD's critics contend the NYPD has
      disproportionately targeted poor, black and Hispanic communities. METHODS: This
      paper analyzes the geographic distribution of MPV arrests from 1992 to 2003 to
      evaluate these alternative perspectives. A sequence of maps identify that the
      focus of MPV arrests shifted over time. RESULTS: In the early 1990s, most MPV
      arrests were recorded in the lower half of Manhattan (NYC's business and cultural
      center) and by the transit police. However, in the later 1990s and into the
      2000s, most MPV arrests were recorded in high poverty, minority communities
      outside the lower Manhattan area and by the NYPD's policing of low-income housing
      projects. CONCLUSION: These findings suggest that current levels of MPV arrests
      in NYC may not be justifiable, at least based solely on the purpose of QOL
      policing. Accordingly, we suggest the NYPD seriously consider less stringent
      measures for public marijuana smokers, especially for use outside of highly
      public locations in recessed locations hidden from open view (like the stairwell
      of a housing project). Alternatives could include Desk Appearance Tickets, fines,
      or simply requiring smokers to desist, discard their product, and move along.

PMID- 16889659
TI  - Genetic structure and evolution of the Vps25 family, a yeast ESCRT-II component.
AB  - BACKGROUND: Vps25p is the product of yeast gene VPS25 and is found in an
      endosomal sorting complex required for transport (ESCRT)-II, along with Vps22p
      and Vps36p. This complex is essential for sorting of ubiquitinated biosynthetic
      and endosomal cargoes into endosomes. RESULTS: We found that VPS25 is a highly
      conserved and widely expressed eukaryotic gene, with single orthologs in
      chromalveolate, excavate, amoebozoan, plant, fungal and metazoan species. Two
      paralogs were found in Trichomonas vaginalis. An ortholog was strikingly absent
      from the Encephalitozoon cuniculi genome. Intron positions were analyzed in VPS25
      from 36 species. We found evidence for five ancestral VPS25 introns, intron loss,
      and single instances of intron gain (a Paramecium species) and intron slippage
      (Theileria species). Processed pseudogenes were identified in four mammalian
      genomes, with a notable absence in the mouse genome. Two retropseudogenes were
      found in the chimpanzee genome, one more recently inserted, and one evolving from
      a common primate ancestor. The amino acid sequences of 119 Vps25 orthologs are
      aligned, compared with the known secondary structure of yeast Vps25p, and used to
      carry out phylogenetic analysis. Residues in two amino-terminal PPXY motifs
      (motif I and II), involved in dimerization of Vps25p and interaction with Vps22p
      and Vps36p, were closely, but not absolutely conserved. Specifically, motif I was
      absent in Vps25 homologs of chromalveolates, euglenozoa, and diplomonads. A
      highly conserved carboxy-terminal lysine was identified, which suggests Vps25 is
      ubiquitinated. Arginine-83 of yeast Vps25p involved in Vps22p interaction was
      highly, but not absolutely, conserved. Human tissue expression analysis showed
      universal expression. CONCLUSION: We have identified 119 orthologs of yeast
      Vps25p. Expression of mammalian VPS25 in a wide range of tissues, and the
      presence in a broad range of eukaryotic species, indicates a basic role in
      eukaryotic cell function. Intron splice site positions were highly conserved
      across all major eukaryotic species, suggesting an ancestral origin. Amino acid
      sequence analysis showed the consensus for the amino-terminal proline-rich motifs
      is P- [WP]-X-[YF] for motif I (when present) and P-P-[FYL]-[FY] for motif II, and
      that Vps25 may be ubiquitinated.

PMID- 16889661
TI  - Zebrafish promoter microarrays identify actively transcribed embryonic genes.
AB  - We have designed a zebrafish genomic microarray to identify DNA-protein
      interactions in the proximal promoter regions of over 11,000 zebrafish genes.
      Using these microarrays, together with chromatin immunoprecipitation with an
      antibody directed against tri-methylated lysine 4 of Histone H3, we demonstrate
      the feasibility of this method in zebrafish. This approach will allow
      investigators to determine the genomic binding locations of DNA interacting
      proteins during development and expedite the assembly of the genetic networks
      that regulate embryogenesis.

PMID- 16889662
TI  - Robust computational reconstitution - a new method for the comparative analysis
      of gene expression in tissues and isolated cell fractions.
AB  - BACKGROUND: Biological tissues consist of various cell types that differentially
      contribute to physiological and pathophysiological processes. Determining and
      analyzing cell type-specific gene expression under diverse conditions is
      therefore a central aim of biomedical research. The present study compares gene
      expression profiles in whole tissues and isolated cell fractions purified from
      these tissues in patients with rheumatoid arthritis and osteoarthritis. RESULTS:
      The expression profiles of the whole tissues were compared to computationally
      reconstituted expression profiles that combine the expression profiles of the
      isolated cell fractions (macrophages, fibroblasts, and non-adherent cells)
      according to their relative mRNA proportions in the tissue. The mRNA proportions
      were determined by trimmed robust regression using only the most robustly
      expressed genes (1/3 to 1/2 of all measured genes), i.e. those showing the most
      similar expression in tissue and isolated cell fractions. The relative mRNA
      proportions were determined using several different chip evaluation methods,
      among which the MAS 5.0 signal algorithm appeared to be most robust. The computed
      mRNA proportions agreed well with the cell proportions determined by
      immunohistochemistry except for a minor number of outliers. Genes that were
      either regulated (i.e. differentially-expressed in tissue and isolated cell
      fractions) or robustly-expressed in all patients were identified using different
      test statistics. CONCLUSION: Robust Computational Reconstitution uses an
      intermediate number of robustly-expressed genes to estimate the relative mRNA
      proportions. This avoids both the exclusive dependence on the robust expression
      of individual, highly cell type-specific marker genes and the bias towards an
      equal distribution upon inclusion of all genes for computation.

PMID- 16889663
TI  - Organization and post-transcriptional processing of focal adhesion kinase gene.
AB  - BACKGROUND: Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase
      critical for processes ranging from embryo development to cancer progression.
      Although isoforms with specific molecular and functional properties have been
      characterized in rodents and chicken, the organization of FAK gene throughout
      phylogeny and its potential to generate multiple isoforms are not well
      understood. Here, we study the phylogeny of FAK, the organization of its gene,
      and its post-transcriptional processing in rodents and human. RESULTS: A single
      orthologue of FAK and the related PYK2 was found in non-vertebrate species. Gene
      duplication probably occurred in deuterostomes after the echinoderma
      embranchment, leading to the evolution of PYK2 with distinct properties. The
      amino acid sequence of FAK and PYK2 is conserved in their functional domains but
      not in their linker regions, with the absence of autophosphorylation site in C.
      elegans. Comparison of mouse and human FAK genes revealed the existence of
      multiple combinations of conserved and non-conserved 5'-untranslated exons in FAK
      transcripts suggesting a complex regulation of their expression. Four
      alternatively spliced coding exons (13, 14, 16, and 31), previously described in
      rodents, are highly conserved in vertebrates. Cis-regulatory elements known to
      regulate alternative splicing were found in conserved alternative exons of FAK or
      in the flanking introns. In contrast, other reported human variant exons were
      restricted to Homo sapiens, and, in some cases, other primates. Several of these
      non-conserved exons may correspond to transposable elements. The inclusion of
      conserved alternative exons was examined by RT-PCR in mouse and human brain
      during development. Inclusion of exons 14 and 16 peaked at the end of embryonic
      life, whereas inclusion of exon 13 increased steadily until adulthood. Study of
      various tissues showed that inclusion of these exons also occurred, independently
      from each other, in a tissue-specific fashion. CONCLUSION: The alternative coding
      exons 13, 14, 16, and 31 are highly conserved in vertebrates and their inclusion
      in mRNA is tightly but independently regulated. These exons may therefore be
      crucial for FAK function in specific tissues or during development. Conversely
      pathological disturbance of the expression of FAK and of its isoforms could lead
      to abnormal cellular regulation.

PMID- 16889664
TI  - Identification, cloning and characterization of a novel 47 kDa murine PKA C
      subunit homologous to human and bovine Cbeta2.
AB  - BACKGROUND: Two main genes encoding the catalytic subunits Calpha and Cbeta of
      cyclic AMP dependent protein kinase (PKA) have been identified in all vertebrates
      examined. The murine, bovine and human Cbeta genes encode several splice
      variants, including the splice variant Cbeta2. In mouse Cbeta2 has a relative
      molecular mass of 38 kDa and is only expressed in the brain. In human and bovine
      Cbeta2 has a relative molecular mass of 47 kDa and is mainly expressed in
      lymphoid tissues. RESULTS: We identified a novel 47 kDa splice variant encoded by
      the mouse Cbeta gene that is highly expressed in lymphoid cells. Cloning,
      expression, and production of a sequence-specific antiserum and characterization
      of PKA catalytic subunit activities demonstrated the 47 kDa protein to be a
      catalytically active murine homologue of human and bovine Cbeta2. Based on the
      present results and the existence of a human brain-specifically expressed Cbeta
      splice variant designated Cbeta4 that is identical to the former mouse Cbeta2
      splice variant, the mouse splice variant has now been renamed mouse Cbeta4.
      CONCLUSION: Murine lymphoid tissues express a protein that is a homologue of
      human and bovine Cbeta2. The murine Cbeta gene encodes the splice variants
      Cbeta1, Cbeta2, Cbeta3 and Cbeta4, as is the case with the human Cbeta gene.

PMID- 16889665
TI  - Development and evaluation of different normalization strategies for gene
      expression studies in Candida albicans biofilms by real-time PCR.
AB  - BACKGROUND: Candida albicans biofilms are commonly found on indwelling medical
      devices. However, the molecular basis of biofilm formation and development is not
      completely understood. Expression analysis of genes potentially involved in these
      processes, such as the ALS (Agglutinine Like Sequence) gene family can be
      performed using quantitative PCR (qPCR). In the present study, we investigated
      the expression stability of eight housekeeping genes potentially useful as
      reference genes to study gene expression in Candida albicans (C. albicans)
      biofilms, using the geNorm Visual Basic Application (VBA) for Microsoft Excel. To
      validate our normalization strategies we determined differences in ALS1 and ALS3
      expression levels between C. albicans biofilm cells and their planktonic
      counterparts. RESULTS: The eight genes tested in this study are ranked according
      to their expression stability (from most stable to least stable) as follows: ACT1
      (beta-actin)/PMA1 (adenosine triphosphatase), RIP (ubiquinol cytochrome-c
      reductase complex component), RPP2B (cytosolic ribosomal acidic protein P2B),
      LSC2 (succinyl-CoA synthetase beta-subunit fragment), IMH3 (inosine-5'
      monophosphate dehydrogenase fragment), CPA1 (carbamoyl-phosphate synthethase
      small subunit) and GAPDH (glyceraldehyde-3-phosphate dehydrogenase). Our data
      indicate that five genes are necessary for accurate and reliable normalization of
      gene expression data in C. albicans biofilms. Using different normalization
      strategies, we found a significant upregulation of the ALS1 gene and
      downregulation of the ALS3 gene in C. albicans biofilms grown on silicone disks
      in a continous flow system, the CDC reactor (Centre for Disease Control), for 24
      hours. CONCLUSION: In conclusion, we recommend the use of the geometric mean of
      the relative expression values from the five housekeeping genes (ACT1, PMA1, RIP,
      RPP2B and LSC2) for normalization, when analysing differences in gene expression
      levels between C. albicans biofilm cells and planktonic cells. Validation of the
      normalization strategies described above showed that the ALS1 gene is
      overexpressed and the ALS3 gene is underexpressed in C. albicans biofilms grown
      on silicone in the CDC reactor for 24 hours.

PMID- 16889666
TI  - Systemic zoledronate treatment both prevents resorption of allograft bone and
      increases the retention of new formed bone during revascularization and
      remodelling. A bone chamber study in rats.
AB  - BACKGROUND: In osteonecrosis the vascular supply of the bone is interrupted and
      the living cells die. The inorganic mineral network remains intact until
      ingrowing blood vessels invade the graft. Accompanying osteoclasts start to
      resorb the bone trabeculae and gradually replace the bone. If the osteonecrosis
      occurs in mechanically loaded parts, like in the subchondral bone of a loaded
      joint, the remodelling might lead to a weakening of the bone and, in consequence
      to a joint collapse. Systemic bisphosphonate treatment can reduce the resorption
      of necrotic bone. In the present study we investigate if zoledronate, the most
      potent of the commercially available bisphosphonates, can be used to reduce the
      amount or speed of bone graft remodeling. METHODS: Bone grafts were harvested and
      placed in a bone chamber inserted into the tibia of a rat. Host tissue could grow
      into the graft through openings in the chamber. Weekly injections with 1.05
      microg zoledronate or saline were given subcutaneously until the rats were
      harvested after 6 weeks. The specimens were fixed, cut and stained with
      haematoxylin/eosin and used for histologic and histomorphometric analyses.
      RESULTS: By histology, the control specimens were almost totally resorbed in the
      remodeled area and the graft replaced by bone marrow. In the zoledronate treated
      specimens, both the old graft and new-formed bone remained and the graft
      trabeculas were lined with new bone. By histomorphometry, the total amount of
      bone (graft+ new bone) within the remodelled area was 35 % (SD 13) in the
      zoledronate treated grafts and 19 % (SD 12) in the controls (p = 0.001). Also the
      amount of new bone was increased in the treated specimens (22 %, SD 7) compared
      to the controls (14 %, SD 9, p = 0.032). CONCLUSION: We show that zoledronate can
      be used to decrease the resorption of both old graft and new-formed bone during
      bone graft remodelling. This might be useful in bone grafting procedure but also
      in other orthopedic conditions, both where necrotic bone has to be remodelled
      i.e. after osteonecrosis of the knee and hip and in Perthes disease, or in high
      load, high turnover conditions like delayed union, periprosthetic osteolysis or
      bone lengthening operations. In our model an increased net formation of new bone
      was found which probably reflects that new bone formed was retained by the action
      of the bisphosphonates rather than a true anabolic effect.

PMID- 16889667
TI  - ECT associated musical hallucinations in an elderly patient: a case report.
AB  - Electro Convulsive Therapy (ECT) is a medical treatment for severe mental illness
      in which small, carefully controlled electricity is applied to the brain. This
      electric stimulation is done in conjunction with anesthesia and muscle relaxant
      medications to produce a mild generalized seizure. This is used to treat a
      variety of psychiatric disorders. This is most effective in the treatment of
      severe depression providing a rapid relief. We report and discuss an unusual
      presentation of a ninety three year old lady with a diagnosis of Major Depressive
      Disorder, Recurrent, Severe with Psychotic features (296.34) who experienced
      musical hallucinations whilst she was treated on ECT. Clinically there was an
      inverse relationship between the biological symptoms of depression and musical
      hallucination during the ECT management. Though similar reports have never been
      reported earlier, we noticed a good association between the initiation of ECT and
      musical hallucination in our patient. The patient stopped experiencing musical
      hallucinations and improved of her biological symptoms of depression completely
      after the full course of ECT.

PMID- 16889668
TI  - The integrase interactor 1 (INI1) proteins facilitate Tat-mediated human
      immunodeficiency virus type 1 transcription.
AB  - Integration of human immunodeficiency virus type 1 (HIV-1) into the host genome
      is catalyzed by the viral integrase (IN) and preferentially occurs within
      transcriptionally active genes. During the early phase of HIV-1 infection, the
      incoming viral preintegration complex (PIC) recruits the integrase interactor 1
      (INI1)/hSNF5, a chromatin remodeling factor which directly binds to HIV-1 IN. The
      impact of this event on viral replication is so far unknown, although it has been
      hypothesized that it could tether the preintegration complex to transcriptionally
      active genes, thus contributing to the bias of HIV integration for these regions
      of the genome. Here, we demonstrate that while INI1 is dispensable for HIV-1
      transduction, it can facilitate HIV-1 transcription by enhancing Tat function.
      INI1 bound to Tat and both the repeat (Rpt) 1 and Rpt 2 domains of INI1 were
      required for efficient activation of Tat-mediated transcription. These results
      suggest that the incoming PICs might recruit INI1 to facilitate proviral
      transcription.

PMID- 16889670
TI  - Development and testing of innovative patient resources for the management of
      coronary heart disease (CHD): a descriptive study.
AB  - BACKGROUND: Although heart disease is a major cause of morbidity and mortality
      the majority of patients do not access existing rehabilitation programs and
      patient resources are not designed to facilitate patient choice and decision
      making. The objective of this study was to develop and test a series of risk
      factor modules and corresponding patient information leaflets for secondary
      prevention of CHD. METHODS: In phase one, a series of risk factor modules and
      management options were developed following analysis of literature and interviews
      with health professionals. In phase two, module information leaflets were
      developed using published guidelines and interviews of people with CHD. In phase
      three, the leaflets were tested for quality (DISCERN), readability (Flesch) and
      suitability (SAM) and were compared to the existing cardiac rehabilitation (CR)
      information leaflet. Finally, the patients assessed the leaflets for content and
      relevance. RESULTS: Four key risk factors identified were cholesterol, blood
      pressure, smoking and physical inactivity. Choice management options were
      selected for each risk factor and included medical consultation, intensive health
      professional led program, home program and self direction. Patient information
      needs were then identified and leaflets were developed. DISCERN quality scores
      were high for cholesterol (62/80), blood pressure (59/80), smoking (62/80) and
      physical activity (62/80), all scoring 4/5 for overall rating. The mean Flesch
      readability score was 75, representing "fairly easy to read", all leaflets scored
      in the superior category for suitability and were reported to be easy to
      understand, useful and motivating by persons with CHD risk factors. The developed
      leaflets scored higher on each assessment than the existing CR leaflets.
      CONCLUSION: Using a progressive three phase approach, a series of risk factor
      modules and information leaflets were successfully developed and tested. The
      leaflets will contribute to shared-decision making and empowerment for persons
      with CHD.

PMID- 16889669
TI  - Failure of catecholamines to shift T-cell cytokine responses toward a Th2 profile
      in patients with rheumatoid arthritis.
AB  - To further understand the role of neuro-immunological interactions in the
      pathogenesis of rheumatoid arthritis (RA), we studied the influence of
      sympathetic neurotransmitters on cytokine production of T cells in patients with
      RA. T cells were isolated from peripheral blood of RA patients or healthy donors
      (HDs), and stimulated via CD3 and CD28. Co-incubation was carried out with
      epinephrine or norepinephrine in concentrations ranging from 10(-5) M to 10(-11)
      M. Interferon (IFN)-gamma, tumour necrosis factor (TNF)-alpha, interleukin (IL)
      4, and IL-10 were determined in the culture supernatant with enzyme-linked
      immunosorbent assay. In addition, IFN-gamma and IL-10 were evaluated with
      intracellular cytokine staining. Furthermore, basal and agonist-induced cAMP
      levels and catecholamine-induced apoptosis of T cells were measured.
      Catecholamines inhibited the synthesis of IFN-gamma, TNF-alpha, and IL-10 at a
      concentration of 10(-5) M. In addition, IFN-gamma release was suppressed by 10(
      7) M epinephrine. Lower catecholamine concentrations exerted no significant
      effect. A reduced IL-4 production upon co-incubation with 10(-5) M epinephrine
      was observed in RA patients only. The inhibitory effect of catecholamines on IFN
      gamma production was lower in RA patients as compared with HDs. In RA patients, a
      catecholamine-induced shift toward a Th2 (type 2) polarised cytokine profile was
      abrogated. Evaluation of intracellular cytokines revealed that CD8-positive T
      cells were accountable for the impaired catecholaminergic control of IFN-gamma
      production. The highly significant negative correlation between age and
      catecholamine effects in HDs was not found in RA patients. Basal and stimulated
      cAMP levels in T-cell subsets and catecholamine-induced apoptosis did not differ
      between RA patients and HDs. RA patients demonstrate an impaired inhibitory
      effect of catecholamines on IFN-gamma production together with a failure to
      induce a shift of T-cell cytokine responses toward a Th2-like profile. Such an
      unfavorable situation is a perpetuating factor for inflammation.

PMID- 16889672
TI  - Counselling and knowledge about contraceptive mode of action among married women;
      a cross-sectional study.
AB  - BACKGROUND: Family planning counselling which covers knowledge transfer about
      contraceptive mode of action, by enabling informed choice, improves compliance to
      and efficiency of contraceptive methods. The objective of this study was to
      investigate associations between family planning counselling, counsellor and
      correct knowledge about mode of action of modern contraceptive methods among
      married women. METHODS: For this cross-sectional study, stratified (according to
      current modern contraceptive method in use) random sampling was performed from
      the registries of two primary health care centres. Main outcomes were; prevalence
      of family planning counselling, professional background of the counsellor and
      correct knowledge about mode of action. A semi-structured questionnaire developed
      by the researchers was applied via face-to-face interview. The answers about mode
      of action were categorized as correct vs. incorrect by consensus rating. RESULTS:
      Prevalence of counselling and correct knowledge about mode of action was 49.0%
      and 39.3%, respectively. Higher educated women were significantly more likely to
      know the mode of action (p < 0.001). Being counselled by a physician (54.1%, n =
      120) was not associated with correct knowledge about mode of action (p = 0.79).
      Non-barrier method users were less educated (p = 0.001), more often counselled
      (60.8% vs. 8.0%) and less knowledgeable (p < 0.001) about mode of action of their
      contraceptive method, compared to condom users. Nevertheless, counselled non
      barrier method users were significantly more likely to know the correct mode of
      action of their chosen method (p = 0.021) than counselled condom users.
      CONCLUSION: The beneficial effect of counselling on knowledge about mode of
      action of the more complicated, medical (non-barrier) contraceptive methods
      suggests that the use of family planning counselling services in primary health
      care should be promoted; furthermore, counselling strategies and content should
      be re-structured for better efficacy.

PMID- 16889671
TI  - Magnetic resonance lung function--a breakthrough for lung imaging and functional
      assessment? A phantom study and clinical trial.
AB  - BACKGROUND: Chronic lung diseases are a major issue in public health. A serial
      pulmonary assessment using imaging techniques free of ionizing radiation and
      which provides early information on local function impairment would therefore be
      a considerably important development. Magnetic resonance imaging (MRI) is a
      powerful tool for the static and dynamic imaging of many organs. Its application
      in lung imaging however, has been limited due to the low water content of the
      lung and the artefacts evident at air-tissue interfaces. Many attempts have been
      made to visualize local ventilation using the inhalation of hyperpolarized gases
      or gadolinium aerosol responding to MRI. None of these methods are applicable for
      broad clinical use as they require specific equipment. METHODS: We have shown
      previously that low-field MRI can be used for static imaging of the lung. Here we
      show that mathematical processing of data derived from serial MRI scans during
      the respiratory cycle produces good quality images of local ventilation without
      any contrast agent. A phantom study and investigations in 85 patients were
      performed. RESULTS: The phantom study proved our theoretical considerations. In
      99 patient investigations good correlation (r = 0.8; p < or = 0.001) was seen for
      pulmonary function tests and MR ventilation measurements. Small ventilation
      defects were visualized. CONCLUSION: With this method, ventilation defects can be
      diagnosed long before any imaging or pulmonary function test will indicate
      disease. This surprisingly simple approach could easily be incorporated in
      clinical routine and may be a breakthrough for lung imaging and functional
      assessment.

PMID- 16889673
TI  - Patient, prisoner or person?
AB  - Case studies provide rich descriptions of significant vignettes that highlight
      atypical systemic or clinical problems and identify potentially important
      research questions. The case study presented by Venters, Razvi, Tobia and Drucker
      (2006) describes an unfortunate set of events pertaining to an individual's
      experience as they were failed by s several systems all at once and neglected for
      having had experience with an addiction. This commentary provides some remarks on
      the case study with respect to differing institutional narratives as they pertain
      to lived experience in the context of everyday life. It is suggested that, in the
      special case of addiction, the mistreatment of the subject of the case study, Mr.
      Ortiz, is not an exception to the norm, but the norm itself for people living
      with addictions and their families.

PMID- 16889674
TI  - Regulatory role of pro-Th1 and pro-Th2 cytokines in modulating the activity of
      Th1 and Th2 cells when B cell and macrophages are used as antigen presenting
      cells.
AB  - BACKGROUND: Presence of antigen presenting cells, expression of costimulatory
      molecules, the strength of first signal and cytokine milieu are quite important
      in influencing the reactivation of differentiated Th1 and Th2 cells. RESULTS: In
      the present study, we have analyzed the concerted action of pro-Th1 and pro-Th2
      cytokines in the presence of B cells, peritoneal and splenic macrophages as
      antigen presenting cells and varied concentration of first (anti-CD3 Ab) and
      second (B7-1 transfectant) signals on the proliferation and cytokine secretion by
      Th1 and Th2 cells. Interesting observations were made that IFN-gamma
      significantly augmented the secretion of IL-4 by Th2 cells when either B cells or
      splenic or peritoneal macrophages were used as APC. Further, IFN-gamma
      significantly inhibited the proliferation of Th1 cells only in the presence of
      peritoneal macrophages. We have also observed that B cells could significantly
      respond to cytokines to further enhance the proliferation and cytokine release by
      Th1 and Th2 cells. But not much effect on addition of exogenous cytokines IL-1,
      IL-4, IL-5, IL-12 was observed on the proliferation of Th1 and Th2 cells in the
      presence of macrophages. In contrast, both IFN-gamma and IL-2 significantly
      enhanced the production of IL-4 and IL-5 respectively, by Th2 cells in presence
      of B cells, splenic and peritoneal macrophages. Another important observation was
      that the addition of B7-1 transfectants in the cultures, which were stimulated
      with low dose of anti-CD3 Ab significantly, enhanced the proliferation and
      cytokine secretion. CONCLUSION: This study indicates involvement of different
      type of APCs, cytokine milieu, dose of first and second signals in a concerted
      manner in the outcome of the immune response. The significance of this study is
      that the immunization with antigen along with costimulatory molecules may
      significantly reduce the dose of antigen and can generate better immune response
      than antigen alone.

PMID- 16889675
TI  - Blood-neural barrier: intercellular communication at glio-vascular interface.
AB  - The blood-neural barrier (BNB), including blood-brain barrier (BBB) and blood
      retinal barrier (BRB), is an endothelial barrier constructed by an extensive
      network of endothelial cells, astrocytes and neurons to form functional
      "neurovascular units", which has an important role in maintaining a precisely
      regulated microenvironment for reliable neuronal activity. Although failure of
      the BNB may be a precipitating event or a consequence, the breakdown of BNB is
      closely related with the development and progression of CNS diseases. Therefore,
      BNB is most essential in the regulation of microenvironment of the CNS. The BNB
      is a selective diffusion barrier characterized by tight junctions between
      endothelial cells, lack of fenestrations, and specific BNB transporters. The BNB
      have been shown to be astrocyte dependent, for it is formed by the CNS capillary
      endothelial cells, surrounded by astrocytic end-foot processes. Given the
      anatomical associations with endothelial cells, it could be supposed that
      astrocytes play a role in the development, maintenance, and breakdown of the BNB.
      Therefore, astrocytes-endothelial cells interaction influences the BNB in both
      physiological and pathological conditions. If we better understand mutual
      interactions between astrocytes and endothelial cells, in the near future, we
      could provide a critical solution to the BNB problems and create new
      opportunities for future success of treating CNS diseases. Here, we focused
      astrocyte-endothelial cell interaction in the formation and function of the BNB.

PMID- 16889676
TI  - Structural conservation and food habit-related liver expression of uncoupling
      protein 2 gene in five major Chinese carps.
AB  - The full-length cDNA of grass carp (Ctenopharyngodon idellus) and silver carp
      (Hypophthalmichthys molitrix) uncoupling protein 2 (UCP2) was obtained from
      liver. The grass carp UCP2 cDNA was determined to be 1152 bp in length with an
      open reading frame that encodes 310 amino acids. Five introns (Intron 3, 4, 5, 6
      and 7) in the translated region, and partial sequence of Intron 2 in the
      untranslated region of grass carp UCP2 gene were also obtained. Gene structure
      comparison between grass carp and mammalian (human and mouse) UCP2 gene shows
      that, the UCP2 gene structure of grass carp is much similar to that of human and
      mouse. Partial UCP2 cDNA sequences of bighead carp (Aristichthys nobilis) and mud
      carp (Cirrhinus molitorella), were further determined. Together with the common
      carp (Cyprinus carpio) UCP2 sequence from GenBank (AJ243486), multiple alignment
      result shows that the nucleotide and amino acid sequences of the UCP2 gene, were
      highly conserved among the five major Chinese carps that belong to four
      subfamilies. Using beta-actin as control, the ratio UCP2/beta-actin mRNA (%) was
      determined to be 149.4 +/- 15.6 (common carp), 127.4 +/- 22.1(mud carp), 96.7 +/-
      12.7 (silver carp), 94.1 +/- 26.8 (bighead carp) and 63.7 +/- 16.2 (grass carp).
      The relative liver UCP2 expression of the five major Chinese carps, shows a close
      relationship with their food habit: benthos and detritus-eating fish (common carp
      and mud carp) > planktivorious fish (silver carp and bighead carp) > herbivorous
      fish (grass carp). We suggest that liver UCP2 might be important for Chinese
      carps to detoxify cyanotoxins and bacteria in debris and plankton food.

PMID- 16889678
TI  - Genetic variation and species identification of Thai Boesenbergia (Zingiberaceae)
      analyzed by chloroplast DNA polymorphism.
AB  - Genetic variation and molecular phylogeny of 22 taxa representing 14 extant
      species and 3 unidentified taxa of Boesenbergia in Thailand and four outgroup
      species (Cornukaempferia aurantiflora, Hedychium biflorum, Kaempferia parviflora,
      and Scaphochlamys rubescens) were examined by sequencing of 3 chloroplast (cp)
      DNA regions (matK, psbA-trnH and petA-psbJ). Low interspecific genetic divergence
      (0.25-1.74%) were observed in these investigated taxa. The 50% majority-rule
      consensus tree constructed from combined chloroplast DNA sequences allocated
      Boesenbergia in this study into 3 different groups. Using psbA-1F/psbA-3R
      primers, an insertion of 491 bp was observed in B. petiolata. Restriction
      analysis of the amplicon (380-410 bp) from the remaining species with Rsa I
      further differentiated Boesenbergia to 2 groupings; I (B. basispicata, B.
      longiflora, B. longipes, B. plicata, B.pulcherrima, B. tenuispicata, B. thorelii,
      B. xiphostachya, Boesenbergia sp.1 and Boesenbergia sp.3; phylogenetic clade A)
      that possesses a Rsa I restriction site and II (B.curtisii, B. regalis, B.
      rotunda and Boesenbergia sp.2; phylogenetic clade B and B. siamensis;
      phylogenetic clade C) that lacks a restriction site of Rsa I. Single nucleotide
      polymorphism (SNP) and indels found can be unambiguously applied to authenticate
      specie-origin of all investigated samples and revealed that Boesenbergia sp.1,
      Boesenbergia sp.2 and B. pulcherrima (Mahidol University, Kanchanaburi), B. cf.
      pulcherrima1 (Prachuap Khiri Khan) and B. cf. pulcherrima2 (Thong Pha Phum,
      Kanchanaburi) are B. plicata, B. rotunda and B. pulcherrima, respectively. In
      addition, molecular data also suggested that Boesenbergia sp.3 should be further
      differentiated from B. longiflora and regarded as a newly unidentified
      Boesenbergia species.

PMID- 16889677
TI  - The potato transcriptional co-activator StMBF1 is up-regulated in response to
      oxidative stress and interacts with the TATA-box binding protein.
AB  - To gain a better understanding on the function of the potato Solanum tuberosum
      Multiprotein Bridging Factor 1 protein (StMBF1) its interaction with the TATA box
      binding protein (TBP) was demonstrated. In addition we reported that StMBF1
      rescues the yeast mbf1 mutant phenotype, indicating its role as a plant co
      activator. These data reinforce the hypothesis that MBF1 function is also
      conserved among non closely related plant species. In addition, measurement of
      StMBF1 protein level by Western blot using anti-StMBF1 antibodies indicated that
      the protein level increased upon H(2)O(2) and heat shock treatments. However, the
      potato beta-1,3-glucanase protein level was not changed under the same
      experimental conditions. These data indicate that StMBF1 participates in the cell
      stress response against oxidative stress allowing us to suggest that MBF1 genes
      from different plant groups may share similar functions.

PMID- 16889679
TI  - Anti-CHH antibody causes impaired hyperglycemia in Penaeus monodon.
AB  - Crustacean hyperglycemic hormone (CHH) plays a major role in controlling glucose
      level in the haemolymph and also triggers important events during molting and
      reproductive cycles. In Penaeus monodon, three types of CHH, namely Pem-CHH1, Pem
      CHH2 and Pem-CHH3, have been previously characterized. In this study, mouse
      polyclonal antibody was raised against recombinant Pem-CHH1 that was expressed in
      Escherichia coli. The anti-Pem-CHH1 antibody recognized all three types of Pem
      CHHs but did not cross-react with either related hormone, molt-inhibiting hormone
      of P. monodon, or unrelated human growth hormone. The hyperglycemic activity in
      the extract from the eyestalk neural tissues was significantly depleted after
      incubating with anti-Pem-CHH antibody. Direct injection of the antibody into
      shrimp caused about 30-50% reduction in the haemolymph glucose level. The result
      demonstrates the ability of anti-Pem-CHH1 antibody to deplete the activity of CHH
      in vivo, and thus provides a possibility of using anti-Pem-CHH1 antibody to
      inhibit the hormone activity as a strategy to modulate growth and reproduction in
      this species.

PMID- 16889680
TI  - Oxidative stress is decreased in off-pump versus on-pump coronary artery surgery.
AB  - Oxidative stress occurs in patients undergoing coronary artery bypass operation.
      The aim of this study was to investigate the difference in oxidative stress in
      off-pump versus on-pump coronary artery bypass surgery. In the present study, in
      serial blood samples, plasma malondialdehyde (MDA) as index of lipid
      peroxidation, red blood cells glutathione peroxidase (GPx) and superoxide
      dismutase (SOD) were measured to compare the extent of oxidative stress in 30
      patients undergoing OPCAB (off-pump coronary artery bypass grafting), 12 patients
      undergoing CABG (on-pump coronary artery bypass grafting) and 18 healthy
      controls. In CABG group, MDA levels increased significantly from 2.87 +/- 0.62
      nmol/mL before anesthesia and 2.87 +/- 0.65 nmol/mL after anesthesia to 3.05 +/-
      0.66 nmol/mL after ischemia (p < 0.05). Similarly, SOD levels also elevated
      significantly from 661.58 +/- 78.70 U/g Hb before anesthesia and 659.42 +/- 81.21
      U/g Hb anesthesia induction to 678.08 +/- 75.80 U/g Hb after ischemia (p < 0.01,
      p < 0.01, respectively). In OPCAB group, only SOD levels increased from 581.73 +/
      86.24 U/g Hb anesthesia induction to 590.90 +/- 88.90 U/g Hb after reperfusion
      (p < 0.05). Glutathione peroxidase levels were not changed according to blood
      collection times in both of CABG group or OPCAB group (p > 0.05). Our results
      show that only mild signs of oxidative stress is found after reperfusion in OPCAB
      operation compared with CABG operation. Further studies are needed in order to
      confirm this hypothesis.

PMID- 16889681
TI  - Characteristics of thiamine uptake by the BeWo human trophoblast cell line.
AB  - Little is known concerning the mechanisms responsible for the transplacental
      transfer of thiamine. So, the aim of this work was to characterize the placental
      uptake of thiamine from the maternal circulation, by determining the
      characteristics of 3H-thiamine uptake by a human trophoblast cell line (BeWo).
      Uptake of (3)H-thiamine (50-100 nM) by BeWo cells was: 1) temperature-dependent
      and energy-independent; 2) pH-dependent (uptake increased as the extracellular
      medium pH decreased); 3) Na(+)-dependent and Cl(-)-independent; 4) not inhibited
      by the thiamine structural analogs amprolium, oxythiamine and thiamine
      pyrophosphate; 5) inhibited by the unrelated organic cations guanidine, N
      methylnicotinamide, tetraethylammonium, clonidine and cimetidine; 6) inhibited by
      the organic cation serotonin, and by two selective inhibitors of the serotonin
      plasmalemmal transporter (hSERT), fluoxetine and desipramine. We conclude that
      (3)H-thiamine uptake by BeWo cells seems to occur through a process distinct from
      thiamine transporter-1 (hThTr-1) and thiamine transporter-2 (hThTr-2). Rather, it
      seems to involve hSERT. Moreover, chronic (48 h) exposure of cells to caffeine (1
      microM) stimulated and chronic exposure to xanthohumol and iso-xanthohumol (1 and
      0.1 microM, respectively) inhibited (3)H-thiamine uptake, these effects being not
      mediated through modulation of the expression levels of either hThTr-1 or hSERT
      mRNA.

PMID- 16889682
TI  - Putrescine transport in a cyanobacterium Synechocystis sp. PCC 6803.
AB  - The transport of putrescine into a moderately salt tolerant cyanobacterium
      Synechocystis sp. PCC 6803 was characterized by measuring the uptake of
      radioactively-labeled putrescine. Putrescine transport showed saturation kinetics
      with an apparent K(m) of 92 +/- 10 microM and V(max) of 0.33 +/- 0.05 nmol/min/mg
      protein. The transport of putrescine was pH-dependent with highest activity at pH
      7.0. Strong inhibition of putrescine transport was caused by spermine and
      spermidine whereas only slight inhibition was observed by the addition of various
      amino acids. These results suggest that the transport system in Synechocystis sp.
      PCC 6803 is highly specific for polyamines. Putrescine transport is energy
      dependent as evidenced by the inhibition by various metabolic inhibitors and
      ionophores. Slow growth was observed in cells grown under salt stress. Addition
      of low concentration of putrescine could restore growth almost to the level
      observed in the absence of salt stress. Upshift of the external osmolality
      generated by either NaCl or sorbitol caused an increased putrescine transport
      with an optimum 2-fold increase at 20 mosmol/kg. The stimulation of putrescine
      transport mediated by osmotic upshift was abolished in chloramphenicol-treated
      cells, suggesting possible involvement of an inducible transport system.

PMID- 16889683
TI  - Characterization of late-onset citrullinemia 1 in a Korean patient: confirmation
      by argininosuccinate synthetase gene mutation analysis.
AB  - A 16-month old boy was referred to our hospital for evaluation of recurrent
      generalized tonic clonic seizures. Metabolic evaluation revealed significant
      hyperammonemia (1,112 microg/dl). Amino acid/acylcarnitine screening using tandem
      mass spectrometry showed markedly increased plasma levels of citrulline (1,350
      microM/l) with undetectable levels of arginine and arginosuccinic acid. Urinary
      excretion of citrulline was markedly increased (38,617 microM/g creatinine).
      Brain MRI findings showed diffuse high-signal intensity lesions, that involved
      gray and white matter in both frontal lobes and insula with edematous changes;
      these findings were consistent with the acute stage of citrullinemia (CTLN).
      Mutation analysis of the argininosuccinate synthetase (ASS) gene, in this
      patient, showed a Gly324Ser mutation in exon 13, and a 67-bp duplication mutation
      in exon 15 (c.1128-6_1188dup67). The patient was confirmed as having late-onset
      CTLN1 and treated with anticonvulsants, lactulose enema, protein restricted diet
      and arginine. Here we describe a case of late-onset CTLN1 in a patient by
      biochemical analyses and ASS gene mutation confirmation. This is the first report
      of a Korean patient with late-onset CTLN1 confirmed by ASS gene mutation
      identification.

PMID- 16889684
TI  - Identification of amino acid residues involved in the interaction between measles
      virus Haemagglutin (MVH) and its human cell receptor (signaling lymphocyte
      activation molecule, SLAM).
AB  - Signaling lymphocyte activation molecule (SLAM; also known as CD150) is a newly
      identified cellular receptor for measles virus (MV). The interaction between MV
      Haemagglutin (MVH) and SLAM is an initial step for MV entry. We have identified
      several novel SLAM binding sites at residues S429, T436 and H437 of MVH protein
      and MVH mutants in these residues dramatically decrease the ability to
      interaction with the cell surface SLAM and fail to coprecipitation with SLAM in
      vivo as well as malfunction in syncytium formation. At the same time, K58, S59
      and H61 of SLAM was also identified to be critical for MVH and SLAM binding.
      Further, these residues may be useful targets for the development of measles
      therapy.

PMID- 16889685
TI  - Identification of transmembrane domain of a membrane associated protein NS5 of
      Dendrolimus punctatus cytoplasmic polyhedrosis virus.
AB  - We examined the intracellular localization of NS5 protein of Dendrolimus
      punctatus cytoplasmic polyhedrosis virus (DpCPV) by expressing NS5-GFP fusion
      protein and proteins from deletion mutants of NS5 in baculovirus recombinant
      infected insect Spodoptera frugiperda (Sf-9) cells. It was found that the NS5
      protein was present at the plasma membrane of the cells, and that the N-terminal
      portion of the protein played a key role in the localization. A transmembrane
      region was identified to be present in the N-terminal portion of the protein, and
      the detailed transmembrane domain (SQIHMVWVKSGLVFF, 57-71aa) of N-terminal
      portion of NS5 was further determined, which was accorded with the predicted
      results, these findings suggested that NS5 might have an important function in
      viral life cycle.

PMID- 16889686
TI  - Korean BAC library construction and characterization of HLA-DRA, HLA-DRB3.
AB  - A human bacterial artificial chromosome (BAC) library was constructed with high
      molecular weight DNA extracted from the blood of a male Korean. This Korean BAC
      library contains 100,224 clones of insert size ranging from 70 to 150 kb, with an
      average size of 86 kb, corresponding to a 2.9-fold redundancy of the genome. The
      average insert size was determined from 288 randomly selected BAC clones that
      were well distributed among all the chromosomes. We developed a pooling system
      and three-step PCR screen for the Korean BAC library to isolate desired BAC
      clones, and we confirmed its utility using primer pairs designed for one of the
      clones. The Korean BAC library and screening pools will allow PCR-based screening
      of the Korean genome for any gene of interest. We also determined the allele
      types of HLA-DRA and HLA-DRB3 of clone KB55453, located in the HLA class II
      region on chromosome 6p21.3. The HLA-DRA and DRB3 genes in this clone were
      identified as the DRA*010202 and DRB3*01010201 types, respectively. The haplotype
      found in this library will provide useful information in future human disease
      studies.

PMID- 16889687
TI  - Kinetic properties of extracted lactate dehydrogenase and creatine kinase from
      mouse embryonic stem cell- and neonatal-derived cardiomyocytes.
AB  - Embryonic stem cells (ESCs), representing a population of undifferentiated
      pluripotent cells with both self-renewal and multilineage differentiation
      characteristics, are capable of spontaneous differentiation into cardiomyocytes.
      The present study sought to define the kinetic characterization of lactate
      dehydrogenase (LDH) and creatine kinase (CK) of ESC- and neonatal-derived
      cardiomyocytes. Spontaneously differentiated cardiomyocytes from embryoid bodies
      (EBs) derived from mouse ESC line (Royan B1) and neonatal cardiomyocytes were
      dispersed in a buffer solution. Enzymes were extracted by sonication and
      centrifugation for kinetic evaluation of LDH and CK with spectrophotometric
      methods. While a comparison between the kinetic properties of the LDH and CK of
      both groups revealed not only different Michaelis constants and optimum
      temperatures for LDH but also different Michaelis constants and optimum pH for
      CK, the pH profile of LDH and optimum temperature of CK were similar. In defining
      some kinetic properties of cardiac metabolic enzymes of ESC-derived
      cardiomyocytes, our results are expected to further facilitate the use of ESCs as
      an experimental model.

PMID- 16889688
TI  - A tuber lectin from Arisaema jacquemontii Blume with anti-insect and anti
      proliferative properties.
AB  - A tuber lectin from Arisaema jacquemontii Blume belonging to family Araceae was
      purified by employing a single step affinity chromatography using column of
      asialofetuin-linked amino activated silica beads and the bound lectin was eluted
      with 100 mM glycine-HCl buffer pH 2.5. The purified A. jacquemontii lectin (AJL)
      showed a single protein band with an apparent molecular mass of 13.4 kDa when
      submitted to SDS-polyacrylamide gel electrophoresis under reducing as well as non
      reducing conditions. The native molecular mass of AJL determined by gel
      filtration on a Biogel P-200 column was 52 kDa and its carbohydrate content was
      estimated to be 3.40%. Thus AJL is a tetrameric glycoprotein. The purified lectin
      agglutinated erythrocytes from rabbit but not from human. Its activity was not
      inhibited by any of the mono- and disaccharides tested except N-acetyl-D
      lactosamine having minimal inhibitory sugar concentration (MIC) 25 mM. Among the
      glycoproteins tested only asialofetuin was found to be inhibitory (MIC125
      microg/mL). A single band was obtained in native PAGE at pH 4.5 while PAGE at pH
      8.3 showed two bands. Isoelectric focusing of AJL gave multiple bands in the pI
      range of 4.6-5.5. When incorporated in artificial diet AJL significantly affected
      the development of Bactrocera cucurbitae (Coquillett) larvae indicating the
      possibility of using this lectin in a biotechnological strategy for insect
      management of cucurbits. Larvae fed on artificial diet containing sublethal dose
      of AJL showed a significant decrease in acid phosphatase and alkaline phosphatase
      activity while esterase activity markedly increased as compared to larvae fed on
      diet without lectin. Out of various human cancer cell lines employed in
      sulphorhodamine B (SRB) assay, this lectin was found to have appreciable
      inhibitory effect on the in vitro proliferation of HCT-15, HOP-62, SW-620, HT-29,
      IMR-32, SKOV-3, Colo-205, PC-3, HEP-2 and A-549 cancer cell lines by 82, 77, 73,
      70, 41, 41, 37, 29, 21 and 21% respectively.

PMID- 16889689
TI  - GEDA: new knowledge base of gene expression in drug addiction.
AB  - Abuse of drugs can elicit compulsive drug seeking behaviors upon repeated
      administration, and ultimately leads to the phenomenon of addiction. We developed
      a procedure for the standardization of microarray gene expression data of rat
      brain in drug addiction and stored them in a single integrated database system,
      focusing on more effective data processing and interpretation. Another
      characteristic of the present database is that it has a systematic flexibility
      for statistical analysis and linking with other databases. Basically, we adopt an
      intelligent SQL querying system, as the foundation of our DB, in order to set up
      an interactive module which can automatically read the raw gene expression data
      in the standardized format. We maximize the usability of this DB, helping users
      study significant gene expression and identify biological function of the genes
      through integrated up-to-date gene information such as GO annotation and
      metabolic pathway. For collecting the latest information of selected gene from
      the database, we also set up the local BLAST search engine and nonredundant
      sequence database updated by NCBI server on a daily basis. We find that the
      present database is a useful query interface and data-mining tool, specifically
      for finding out the genes related to drug addiction. We apply this system to the
      identification and characterization of methamphetamine-induced genes' behavior in
      rat brain.

PMID- 16889691
TI  - Oxidative damage of DNA induced by the cytochrome C and hydrogen peroxide system.
AB  - To elaborate the peroxidase activity of cytochrome c in the generation of free
      radicals from H2O2, the mechanism of DNA cleavage mediated by the cytochrome
      c/H2O2 system was investigated. When plasmid DNA was incubated with cytochrome c
      and H2O2, the cleavage of DNA was proportional to the cytochrome c and H2O2
      concentrations. Radical scavengers, such as azide, mannitol, and ethanol,
      significantly inhibited the cytochrome c/H2O2 system-mediated DNA cleavage. These
      results indicated that free radicals might participate in the DNA cleavage by the
      cytochrome c and H2O2 system. Incubation of cytochrome c with H2O2 resulted in a
      time-dependent release of iron ions from the cytochrome c molecule. During the
      incubation of deoxyribose with cytochrome c and H2O2, the damage to deoxyribose
      increased in a time-dependent manner, suggesting that the released iron ions may
      participate in a Fenton-like reaction to produce dOH radicals that may cause the
      DNA cleavage. Evidence that the iron-specific chelator, desferoxamine (DFX),
      prevented the DNA cleavage induced by the cytochrome c/H2O2 system supports this
      mechanism. Thus we suggest that DNA cleavage is mediated via the generation of
      dOH by a combination of the peroxidase reaction of cytochrome c and the Fenton
      like reaction of free iron ions released from oxidatively damaged cytochrome c in
      the cytochrome c/H2O2 system.

PMID- 16889690
TI  - Effective chemopreventive activity of genistein against human breast cancer
      cells.
AB  - Chemopreventive and cytotoxic effect of genistein against human breast cancer
      cell lines was investigated. Genistein inhibited cell proliferation in estrogen
      receptor-positive (MCF-7) and estrogen receptor-negative (MDA-MB-231) human
      breast carcinoma cell lines. Cytochrome P450 (CYP) 1A1-mediated ethoxyresorufin O
      deethylase (EROD)activity was inhibited by genistein in a concentration-dependent
      manner. Genistein significantly inhibited 12-Otetradecanoylphorbol-13-acetate
      (TPA)-induced cyclooxygenase-2 activity and protein expression at the
      concentrations of 10 (p < 0.05), 25 (p < 0.05) and 50 mM (p < 0.01). In addition,
      ornithine decarboxylase (ODC) activity was reduced to 53.8 % of the control after
      6 h treatment with 50 mM genistein in MCF-7 breast cancer cells. These results
      suggest that genistein could be of therapeutic value in preventing human breast
      cancer.

PMID- 16889692
TI  - Insulin resistance does not influence gene expression in skeletal muscle.
AB  - Insulin resistance is commonly observed in patients prior to the development of
      type 2 diabetes and may predict the onset of the disease. We tested the
      hypothesis that impairment in insulin stimulated glucose-disposal in insulin
      resistant patients would be reflected in the gene expression profile of skeletal
      muscle. We performed gene expression profiling on skeletal muscle of insulin
      resistant and insulin sensitive subjects using microarrays. Microarray analysis
      of 19,000 genes in skeletal muscle did not display a significant difference
      between insulin resistant and insulin sensitive muscle. This was confirmed with
      real-time PCR. Our results suggest that insulin resistance is not reflected by
      changes in the gene expression profile in skeletal muscle.

PMID- 16889693
TI  - One step cloning of defined DNA fragments from large genomic clones.
AB  - Recently, the nucleotide sequences of entire genomes became available. This
      information combined with older sequencing data discloses the exact chromosomal
      location of millions of nucleotide markers stored in the databases at NCBI, EMBO
      or DDBJ. Despite having resolved the intron/exon structures of all described
      genes within these genomes with a stroke of a pen, the sequencing data opens up
      other interesting possibilities. For example, the genomic mapping of the end
      sequences of the human, murine and rat BAC libraries generated at The Institute
      for Genomic Research (TIGR), reveals now the entire encompassed sequence of the
      inserts for more than a million of these clones. Since these clones are
      individually stored, they are now an invaluable source for experiments which
      depend on genomic DNA. Isolation of smaller fragments from such clones with
      standard methods is a time consuming process. We describe here a reliable one
      step cloning technique to obtain a DNA fragment with a defined size and sequence
      from larger genomic clones in less than 48 hours using a standard vector with a
      multiple cloning site, and common restriction enzymes and equipment. The only
      prerequisites are the sequences of ends of the insert and of the underlying
      genome.

PMID- 16889695
TI  - [Investigation on wastewater pollution poisoning accident in a smeltery].

PMID- 16889694
TI  - [Relationship of genetic polymorphism in APE1 and ADPRT to risks of chronic
      benzene poisoning].
AB  - OBJECTIVE: To explore the relationship between genetic polymorphisms in
      apurinic/apyrimidinic endonuclease (APE1) and ADP ribosyltransferase (ADPRT) and
      individuals' susceptibility to chronic benzene poison ing (BP). METHODS: A case
      control study was conducted. One hundred and fifty-two B P patients and 152
      workers occupationally exposed to benzene without poisoning manifestations were
      investigated. The mismatched bases combined to create restriction site with
      restrained fragment length polymorphism technique (CRS-RFLP) was used for
      detecting the single nucleotide polymorphisms (SNPs) at Asp148Glu of APE1 gene
      and Val762Ala of ADPRT gene. RESULTS: There was no significant difference in the
      distribution of genotypes of APE1Asp148Glu and ADPRTVal762Ala between the
      patients and the control groups. Compared with individuals having genotype of
      APE1Asp148Glu T/T without habit of alcohol consumption, there was a 4.13 times
      increased risk of BP for the alcohol user with genotype of APE1Asp148Glu T/T (OR
      = 4.13, 95% CI: 1.07 - 15.85, P = 0.03). The analysis of Logistic regression
      showed that smoking may play some role in modifying the risk of cironic benzene
      poisoning (OR = 0.33, 95% CI: 0.14 - 0.75, P = 0.01). CONCLUSION: The genetic
      polymorphisms in APE1Asp148Glu, ADPRTVal762Ala are not related to the risk of BP.
      Potential interaction is found between alcohol consumption and polymorphism of
      APE1Asp148Glu. Further study is needed to elucidate this interaction.

PMID- 16889697
TI  - [One case of acute organophosphorus pesticide poisoning].

PMID- 16889696
TI  - [Association between polymorphisms of XPD gene and susceptibility to chronic
      benzene poisoning].
AB  - OBJECTIVE: To explore the relationship between genetic polymorphisms of XPD gene
      and susceptibility to chronic benzene poisoning. METHODS: A case control study
      was conducted. Eighty patients diagnosed with chronic benzene poisoning and 62
      workers occupationally exposed to benzene who were engaged in the same working
      time and job title as patients were investigated. PCR-RFLP was used for detecting
      the single nucleotide polymorphisms (SNPs) on codon156, codon312 and codon751 of
      XPD gene. RESULTS: There was a 2.903 times (95% CI: 1.054 - 7.959, P = 0.039 2)
      increased risk of chronic benzene poisoning in the subjects carrying XPD 751Gln
      variant allele compared with those carrying XPD 751Lys/Lys genotype, after
      adjusted for sex, length of service, smoking and drinking status. CONCLUSION: The
      subjects with XPD 751Gln variant allele are more susceptive to benzene.

PMID- 16889698
TI  - [Time dependent changes in antioxidation of rat serums and sciatic nerves caused
      by toxicology].
AB  - OBJECTIVE: To study the time dependent antioxidation changes of serum and sciatic
      nerve in rats intoxicated with acrylamide. METHODS: Male Wistar rats weighing 180
      to 220 g were given acrylamide dissolved in physiological saline (40 mg/kg ip 3
      days/week). The control groups received normal saline. The gait was observed and
      antioxidant indexes of rat serum and sciatic nerve were determined on 0, second,
      fourth, sixth, 10th week. RESULTS: With the extension of the intoxication period,
      compared with the control, the contents of glutathione in serum and sciatic nerve
      gradually decreased (P < 0.05; after 6 and 10 weeks to 92% and 77%; after 2, 4, 6
      and 10 weeks to 92%, 82%, 67% and 66%); the levels of malondialdehyde gradually
      increased (P < 0.05; after 4, 6 and 10 weeks to 113%, 118% and 120%; after 4, 6
      and 10 weeks to 153%, 167%, 174%); the abilities of the resistance to reactive
      oxygen species gradually decreased (P < 0.05; after 10 weeks to 82%; after 6 and
      10 weeks to 76% and 71%); the activities of glutathione peroxidase gradually
      increased (P < 0.05; after 2, 4, 6 and 10 weeks to 122%, 130%, 160% and 124%;
      after 4, 6 and 10 weeks to 134%, 152% 164%); the activities of glutathione
      reductase increased at early stage (P < 0.01; after 4 and 6 weeks to 300% and
      217%; after 4 weeks to 142%) and decreased later (P < 0.01; 6 and 10 weeks to 59%
      and 33% in sciatic nerve); the activities of superoxide dismutase increased
      primitively (P < 0.05; after 2 weeks to 110%; after 4 weeks to 124%) and
      decreased later (P < 0.05; after 10 weeks to 85% in serum). The changes of
      antioxidant indexes in serum and sciatic nerve according to gait score were
      similar. The level of MDA in serum was in high correlation (P < 0.01) with that
      in sciatic nerve. The regression coefficients were 0.99 and 0.96 according to the
      administration time and gait score respectively. CONCLUSION: The changes of the
      antioxidant indexes in serum and sciatic nerve of rat treated with acrylamide are
      time dependent. The changes in serum and sciatic nerve are similar but those in
      sciatic nerve are more remarkable.

PMID- 16889699
TI  - [Effects of prenatal exposure to low level lead on learning and memory of rats'
      offspring].
AB  - OBJECTIVE: To explore the effects of prenatal exposure to low level lead on
      learning and memory of rat's offspring. METHODS: The pregnant rats were
      randomizedly divided into 4 groups and provided with doubly evaporated water in
      the control group and 125, 250 and 500 mg/L lead acetate solution via drinking
      water in three exposed groups respectively during the pregnancy. The learning and
      memory ability of 21-day old and 60-day old offsprings were tested by the Morris
      water maze and the shuttling and avoiding dark box respectively. RESULTS: The
      blood and hippocampus lead concentrations of 1-day old and 21-day old offspring
      in the 3 lead-exposed groups were significantly increased compared with the
      control group (P < 0.05), while at the period of 60-day old there was no
      significant difference between them. The time to find the platform in Morris
      water maze for 21-day old and 60-day old offsprings of the 3 lead in the exposed
      groups was significantly increased compared with the control group during the 4
      days training (P < 0.05). The times of initiative avoiding in the shuttling and
      avoiding dark box for 21-day old and 60-day old offsprings in the 3 lead-exposed
      groups were significantly decreased, while the latency of the initiative avoiding
      and latency of the passive avoiding were significantly increased compared with
      the control group (P < 0.05). CONCLUSION: Prenatal exposure to low level lead
      impaired the space learning and memory ability of offsprings of the rats, and
      this kind of influence will continue till the offspring's maturity.

PMID- 16889700
TI  - [Mercury concentration in cerebrospinal fluid in patients with chronic mercury
      poisoning].
AB  - OBJECTIVE: To investigate the changes of mercury (Hg) levels in cerebrospinal
      fluid (CSF) in patients with chronic mercury poisoning and elucidate the
      neurotoxic mechanism of mercury. METHODS: Nine patients with chronic mercury
      poisoning (poisoning group) as well as eight patients without exposure to mercury
      were included in this study. Mercury concentrations of 24 hour urine (U-Hg) and
      CSF (CSF-Hg) were measured with cold-vapor atomic absorption spectrometry-alkali
      stannous chloride method. The concentration of blood (B-Hg) at the same day was
      measured with cold-vapor atomic absorption spectrometry-acidic stannous chloride
      method. In five patients of poisoning group, these concentrations before
      chelation therapy were compared with those after chelation therapy. RESULTS: The
      levels of B-Hg, U-Hg, and CSF-Hg in poisoning group (250.00 +/- 48.54, 160.07 +/-
      91.15, 20.22 +/- 10.21 nmol/L, respectively) were significantly higher than those
      in control group (81.04 +/- 63.01, 24.73 +/- 9.96 nmol/L, undetectable,
      respectively; P < 0.01). In nine patients of poisoning group, CSF-Hg
      concentrations were correlated with B-Hg (r = 0.675, P < 0.05), but not U-Hg.
      After chelation therapy with dimercaptopropane sulfonate in five patients of
      poisoning group, the levels of B-Hg, U-Hg, and CSF-Hg were decreased
      significantly (P < 0.05). The reduction of CSF-Hg was not related with B-Hg and U
      Hg. CONCLUSION: CSF-Hg concentration in chronic mercury poisoning patient is
      increased with the rise of B-Hg, but not U-Hg. When the levels of B-Hg and U-Hg
      drop to normal, the CSF-Hg level is still high enough to be detected. It
      indicates that mercury is combined with protein after entering brain and this
      complex is difficult to cross through blood-cerebral barrier. The complex may
      cause neuromuscular disorder and fremitus in chronic mercury poisoning.

PMID- 16889701
TI  - [Experimental study on lung injury and cell cycle changes in mice induced by
      bitumen fume].
AB  - OBJECTIVE: To investigate the carcinogenic and mutagenic mechanism of bitumen
      fume. METHODS: The experimental mice were forced to inhale the bitumen fume at
      different exposure level (55 mg/m(3), 165 mg/m(3)) and in different time (30
      days, 60 days). The pathological changes of the lung tissue in mice were observed
      with H.E staining. The content of the DNA in the lung tissue of mice and the cell
      circles were determined with flow cytometry. RESULTS: The lesion of the lung
      tissue in mice comprised the atypical hyperplasia of different levels and the
      carcinoma in situ with the increase of the containment time and dosage; the cycle
      index was changed: the number of the G 1 phase cells was decreased, the S phase
      was retarded, the cells entering the G 2/S phase were decreased, the cell
      proliferation index (P I) was increased and the heteroploid DNA index (DI) was
      increased (P < 0.05). The cell index in the 55 mg/m(3) group and the 165 mg/m(3)
      group was higher than that in the control group when the containment time was
      same. The heteroploid DNA index (DI) in the 55 mg/m(3) group was significantly
      higher than that in the 165 mg/m(3) group (P < 0.05 or P < 0.01). When the
      containment dosage was same, the DI in the 60 days treatment group (1.16 +/- 1.51
      x 10(-2), 1.20 +/- 2.3 x 10(-2)) was all significantly higher than those in the
      30 days treatment group (1.14 +/- 8.8 x 10(-2), 1.16 +/- 1.47 x 10(-2)) (P <
      0.05). CONCLUSION: The precancerous lesion in the lung tissue of the mice induced
      by the bitumen fume may be related with the changes of the cell cycle.

PMID- 16889702
TI  - [Effects and significance of gas explosion on expression of NF-kappaB and ICAM1
      in lung tissue of rats].
AB  - OBJECTIVE: To explore the expression of NF-kappaB and ICAM-1 in the gas explosion
      wounded lung of rats and the relationship. METHODS: Digoxin labeled NF-kappaB was
      used as probe. In situ hybridization was performed to detect the NF-kappaB mRNA.
      Immunohistochemistry was used to detect the expression of NF-kappaB and ICAM-1.
      RESULTS: The levels of NF-kappaB mRNA, the expression of NF-kappaB and ICAM-1 in
      the wounded rats were significantly increased and reached their peak two hours
      after injury. Pathology of lung tissue showed that some crachea epithelium
      mucosae were desquamated; congestion, edema of trachea wall and infiltration of
      neutrophilic granulocytes were found; hemorrhage, edema and infiltration of lots
      of inflammatory cells were present in alveolus cells. Electron microscope showed
      that type I, especially type II alveolus epithelia had degeneration and
      desquamation. CONCLUSION: The injury of gas explosion can activate NF-kappaB,
      which has close correlation with the acute injury to lung.

PMID- 16889703
TI  - [Changes of immune function and nutrition state in pelagic fishermen].
AB  - OBJECTIVE: To investigate the effects of long time cruising on fishermen' immune
      function and nutrition state. METHODS: Thirty-two fishermen's lymphocyte subsets,
      immunoglobulin, alexin, prealbumin, albumin, blood fat, hemoglobin serum iron,
      transferrin were tested before and after cruising. RESULTS: The expression of CD
      19 was significantly higher after cruising (P < 0.001) while other cell immune
      functions were not significantly changed. After cruising, the immunoglobulin IgG,
      IgA, alexin C3, B, prealbumin, albumin, transferrin were higher than before
      cruising (P < 0.001). HDL-C was higher (P < 0.05); Apo-B, and serum iron were
      lower (P < 0.01). CONCLUSION: The cruising fishermen' immune function is changed
      significantly; the nutrition state is good, but the serum iron is insufficient
      and in subclinical state.

PMID- 16889704
TI  - [Meta analysis for relationship between exposure of free silicon dioxide and lung
      tumor].
AB  - OBJECTIVE: Meta-analysis is applied to process a systematic, comprehensive
      evaluation on the relationship between silica exposure and lung cancer in order
      to provide scientific evidences for controlling measures and offer a case for
      EBOM. METHODS: According to established entrance standards, the collected
      original articles on silica exposure and lung cancer were classified and put in
      order, then fixed effects model and random effects model were used which suited
      to analyze occupational epidemiology and occupational tumor materials, and their
      correlation intensity were analyzed. First, combined SMR and 95% CI values for
      case-control study and cohort study were calculated respectively. Then all case
      control studies and cohort studies were combined according to different study
      designs, mixed factors adjusted and stratification analysis processed, and their
      SMR and 95% CI calculated respectively. In order to lessen bias or errors, fail
      safe number was calculated. RESULTS: When combining all the cohort study and all
      the case-control study respectively, corresponding combination SMR(cohort) =
      1.93, 95% CI is 0.55 - 6.92; SMR case = 1.73, 95% CI is 1.01 - 2.99; SMR(sum) =
      2.19, 95% CI is 1.45 - 3.31. Statistical test showed a statistically significant
      relationship lied between silica exposure and lung cancer, with P < 0.05.
      CONCLUSION: Middle intensity relation is drawn between silica exposure and lung
      cancer incidence at worksite. This result is consistent with a lot of public
      reports.

PMID- 16889705
TI  - [Investigation on mercury baseline level in urine in healthy population].

PMID- 16889706
TI  - [Effect of occupationally exposed to dioxin on serum oxidative stress indices in
      male workers].

PMID- 16889707
TI  - [Investigation on knowledge, aptitude and perception of protection for iatrogenic
      pollution in clinical lab personnel and evaluation for effect of health
      education].

PMID- 16889708
TI  - [Effects of oxidative stress on nickel sulfate induced testis impairment in
      mice].

PMID- 16889709
TI  - [Determination of trichloroethylene induced DNA damage with 32P-Postlabeling].

PMID- 16889710
TI  - [Model of benzene induced aplastic anemia in mice and pathological changes of
      intervention of Amifostine].

PMID- 16889711
TI  - [Effect of veneer released formaldehyde on neurological behavior of mice].

PMID- 16889712
TI  - [Dynamic inhalation contamination installation in evaluation of detection of
      toxicity of liquid chemicals].

PMID- 16889714
TI  - [Determination of isophorone in air in working places].

PMID- 16889713
TI  - [High performance thin layer chromatography quality assessment of Rogor, methyl
      parathion, methamidophos and dichlorvos in serum].

PMID- 16889715
TI  - [Determination of 1, 2 propylene dichloride in air in working places].

PMID- 16889716
TI  - [Quality control for evaluation of risks of construction project occupational
      diseases].

PMID- 16889717
TI  - [Risks of occupational diseases in production of pharmaceutical products in
      pharmaceutics manufacturing industry].

PMID- 16889718
TI  - [Investigation on occupational norma hexane poisoning accident in population].

PMID- 16889719
TI  - [Moderate ammonia poisoning in one of medical staff rescuing patients with
      ammonia poisoning].

PMID- 16889723
TI  - [The effect of early diagnosis of recurrence and revision after resection of
      primary spine tumors].
AB  - OBJECTIVE: To explore the effect of early diagnosis of recurrence and early
      revision after resection of primary spine tumors. METHODS: From March 1989 to
      September 2005, the relate clinic data of 55 patients with giant cell tumors,
      osteoblastomas, chondrosarcomas and chordomas in spine in big piecemeal and
      current fashion was analysed. RESULTS: In 55 cases, 43 patients were followed up
      and had complete materials. The follow-up time ranged from 1.6 to 16.5 years,
      averagely 5.8 years. Thirty-four patients followed up regularly, and 12 were
      found recurrent, in which one C(1) giant cell tumor was found extensively large 3
      months after initial surgery and was undertaken palliatory curet. The other
      eleven lesions were small and re-operated with wide margin. As a result, six
      patients lived without tumors during the 1 approximately 9.5 years follow-up, one
      patient gave up revision when found recurred again for economic reason, another
      four patients recurred repeatedly, but they persisted in regular follow-up and
      took revision surgeries whenever the recurred lesion were found. As a result, 3
      of them lived without tumor and the other one died of other disease without sign
      of recurrence. In contrast, there were another nine patients who came to follow
      up until they had symptoms and were confirmed recurrent extensively. Two of them
      were excised radically for the tumors located in the relatively easily exposed
      segments of spine and lived without tumor now. While the other seven patients
      only received palliatory curet and all died of tumors. CONCLUSIONS: Regular
      follow-up, early diagnosis of recurrence and early revision need to be regarded
      as part of radical excision and are very important of surgical treatment of
      spinal tumors, which can prolong the patients' survival time.

PMID- 16889722
TI  - [Analysis of the factors affecting the recurrence of giant cell tumor of bone].
AB  - OBJECTIVE: To analyze the clinical factors affecting the recurrence of giant cell
      tumors (GCT) of bone. METHODS: The complete data of 146 cases with GCT were
      reviewed. Thirteen clinical factors were analyzed by chi(2) analysis. And the
      related Campanacci's grade system and Jaffe's grade system was analyzed by
      Crosstabs analysis. Multipal factors were analyzed by Logistic regression
      analysis. RESULTS: Nineteen of 146 cases recurred, and recurrence rate was 13.0%.
      Recurrence rates of curettage and enblock resection groups were 18.8% and 6.3%
      respectively. And recurrence rates of curettage with or without of extensive
      procedure were 12.9% and 38.9%. Five cases had lung metastasis, and two cases
      presented with malignant transformation. The metastasis rate and the rate of
      malignant transformation were 3.4% and 1.4% respectively. The two factors of
      surgery method and burst out of bone-envelope appearance were related with the
      recurrence. Moreover, Logistic regression revealed that the surgery method
      significantly affected the recurrence. And Campanacci's grade system and Jaffe's
      grade system were not related to each other. CONCLUSIONS: Surgery method is the
      main factor affected the recurrence of GCT, and Campanacci's grade system or
      Jaffe's grade system has no prognostic value.

PMID- 16889724
TI  - [Preliminary report of combination chemotherapy including Arsenic trioxide for
      stage III osteosarcoma and Ewing sarcoma].
AB  - OBJECTIVE: To determine the efficacy of Arsenic trioxide combined with other
      chemo agents in patients with metastatic osteosarcoma and Ewing sarcoma. METHODS:
      From December 2002 to June 2005, 32 patients with metastatic osteosarcoma and
      Ewing sarcoma were treated with chemotherapy comprised Arsenic trioxide,
      including 19 male and 13 female, aging from 7 to 32 years. Diagnoses included 27
      cases with osteosarcomas and 5 with Ewing sarcomas. Twenty-five and 7 patients
      had multiple lung and skeletal metastasis respectively. All patients had received
      4 to 6 cycles standard chemotherapy and surgical treatments before the metastatic
      lesions were found. The chemotherapy protocol consisted of Arsenic trioxide, VP
      16 and paclitaxel. Twenty-eight patients accepted 2 cycles, and 4 patients
      accepted 3 cycles chemotherapy. RESULTS: Five patients (15.6%), whose lung focus
      disappeared and no new metastases proved, got complete response (CR); Six
      patients (18.8%) got partial response (PR); In thirteen stable disease (SD)
      patients (40.6%), the metastatic lesions did not reduce in evidence but
      completely calcified in 2 patients and partly calcified in 11 patients; Eight
      patients (25%) whose tumor size was even bigger after the chemotherapy were
      defined as progress disease (PD). The average follow-up period was 20 months
      (ranging from 6 months to 3 years). Three patients were eventually died; The
      disease was progressed in 5 patients, and the tumor growth was controlled in 24
      patients. CONCLUSIONS: Arsenic trioxide is a low-toxic and effective remedy for
      treatment of stage III osteosarcoma and Ewing sarcoma.

PMID- 16889725
TI  - [Functional outcome following shoulder tumor resection and reconstruction].
AB  - OBJECTIVE: To analyze the long-term limb sparing outcomes of various
      reconstructive procedures and complications associated with extensive excision in
      bone tumours of the shoulder girdle. METHODS: Shoulder reconstruction following
      resection of bone tumors of the shoulder girdle was reviewed retrospectively for
      32 patients at the Wesley Hospital or Princess Alexandra Hospital. The
      reconstructions were including arthrodesis (8 cases), allograft-prosthetic
      composite (7 cases), spacer (6 cases), no bone reconstruction (5 cases),
      prosthesis (3 cases), vascular fibular graft (2 cases) and allograft (1 case).
      RESULTS: The average duration of follow-up was 81 months for the 23 patients who
      were still alive at the time of the latest follow-up examination. Functional
      results were related to the type of resection and the method of shoulder
      reconstruction. After intra-articular resection of the proximal humerus with loss
      of the abductor mechanism, arthrodesis resulted in 87% functional score and more
      strength was found after reconstruction with prosthesis or allograft-prosthetic
      composite. Allograft-prosthetic composite had better function (Score 79%) than
      prosthesis alone after intra-articular resection of the humerus because
      reconstruction of the deltoid and the rotator cuff could be performed without
      increased prevalence of complication related to the allograft. After extra
      articular resection of the glenoid cavity and the proximal humerus with abductor
      mechanism, reconstruction with a functional spacer frequently resulted in
      superior subluxation of the implant and only fair function (Score 66%) of the
      shoulder. With two teen-aged patients, a free fibular graft inserted after intra
      articular resection of the proximal humerus led to fair function (Score 73%), to
      be followed by secondary arthrodesis when growth was complete. CONCLUSIONS:
      Indications for the method of reconstruction depend on type of resection, age,
      gender, occupation, the expected functional level and restriction of activity.
      After resection of the abductor mechanism, arthrodesis results in more strength
      and is the preferred option for the young active demanding patients. If the
      abductor mechanism is preserved, allograft-prosthetic composite gives good
      results.

PMID- 16889726
TI  - [Resection and reconstruction for tumors of iliac bone].
AB  - OBJECTIVE: To discuss the resection of tumors, reconstruction of defects.
      METHODS: Sixty-one patients with tumors in ileum were treated surgically in
      People's Hospital from July 1998 to July 2004. The series comprised 38 males and
      23 females with an average age of 43 years old (range from 12 to 78 years old).
      According to Enneking staging system, 36 cases had lesions in region I, 17 cases
      in region I and II, and 8 cases in region I and IV. After tumor resected,
      posterior fixation system of spine was applied to reconstruct the integrality of
      pelvic ring in series of region I cases. The four pedicle screws were implanted
      in the lumbar and sacrum superiorly, pubis and ischium inferiorly. For children
      patients, bone graft or bone cement and Steinmann's pins internal fixation was
      applied to reconstruct the pelvis. RESULTS: Among all the 61 cases, 48 cases
      followed up from 16 months to 6 years. Thirty-three cases were survived and had
      no local recurrence or metastasis. Fifteen cases were dead. Oncology result:
      local recurrence were found in 19.4% patients with region I resection (7/36), the
      resection level was close to acetabulum (in order to reserve the acetabulum), and
      it might be the reason of recurrence. 35.3% of patients (6/17) with region I and
      II resection had local recurrence, the recurrence maybe related to residual tumor
      after curettage. 50.0% of the patients (4/8) with region I and IV resection had
      local recurrence, the tumor residual in sacrum might be the reason of recurrence.
      Functional result: all of the 36 cases received region I resection regained
      normal walking function. The hip joint function was normal in 17 cases received
      tumor curettage, bone cement or hip joint replacement. CONCLUSIONS: The posterior
      fixation system of spine can be used to reconstruct the integrality of pelvic
      ring after resection of iliac tumors. Simple reconstruction is more favorable for
      child patients. Allograft or self-ileum can be implanted in the space of sacral
      wing and residual ileum, and the bone graft is fixed with compressional screw.

PMID- 16889728
TI  - [Diagnosis and treatment for the injury of cervical disc and longitudinal
      ligament].
AB  - OBJECTIVES: To study the diagnosis and treatment for the injury of cervical disc
      and longitudinal ligament. METHODS: From 2001 to 2005, the clinical data of sixty
      three patients with cervical disc and longitudinal ligament injury were studied.
      Early treatment was done based on spinal cord injuries and spinal stabilities by
      X rays and MRI. Early operation was done in fifty-four cases and early non
      operation in nine cases. RESULTS: The follow-up time was six to forty-one months
      in all patients. The neurological recovery was found in two of eight complete SCI
      post-operation, thirty-one in thirty-nine incomplete SCI. Cervical collar or
      plaster orthotic were used in nine cases with four to six weeks. Evidence of
      instability was noted in four patients, who were operated with anterior
      decompression fusion. Neck chronic pain was found in two patients, anterior
      decompression and fusion was done in one with cervical spinal cord compression.
      CONCLUSIONS: MRI examination is the most value measure for the diagnosis of
      cervical disc and longitudinal ligament injury. Early anterior decompression and
      fusion was an important approach for cervical disc and longitudinal ligament
      injury.

PMID- 16889729
TI  - [Comparison percutaneous cervical disc nucleoplasty and cervical discectomy for
      the treatment of cervical disc herniation].
AB  - OBJECTIVE: To compare the therapeutic effect of percutaneous cervical disc
      nucleoplasty (PCN group) and percutaneous cervical discectomy (PCD group) for the
      treatment of cervical disc herniation. METHODS: A retrospective study was carried
      out from July of 2002 to December of 2004, and there were 80 cervical disc
      herniation cases who were operated by PCN (42 cases) or PCD (38 cases). The time
      of operation, clinical result and the stability of cervical spine after operation
      were evaluated and compared between 2 groups. RESULTS: All cases had been
      followed up from 6 months to 26 months, average (12 +/- 5) months on the PCN
      group and (12 +/- 4) months on the PCD group, and there was no significant
      difference on 2 groups (t = -0.06, P = 0.953). All cases had been successfully
      operated. There was significant difference in the operation time between 2 groups
      (t = -21.70, P = 0.000). There was significant difference in the pre- and post
      operation scores of each group (PCN group: t = 14.05, P = 0.000; PCD group: t = 
      14.79, P = 0.000). There was no significant difference in 2 groups of the
      clinical outcomes (z = -0.377, P = 0.706, > 0.05). There was no instability of
      cervical spine cases in 2 groups after operation (P > 0.05), and the cervical
      spine stability was no significant difference in pre- and-operation in each
      group. CONCLUSIONS: PCN and PCD for the treatment of cervical disc herniation
      achieves good outcomes and no difference on the stability of cervical spine. PCN
      and PCD is a safe, minimally invasive, short time of operation, less traumatic
      operation and excellent clinical outcome.

PMID- 16889730
TI  - [Comparison of melatonin receptor mRNA expression in bilateral paravertebral
      muscles in adolescent idiopathic scoliosis].
AB  - OBJECTIVE: To study the change of melatonin receptor mRNA expression in
      paravertebral muscles in adolescent idiopathic scoliosis (AIS), and analyze its
      relationship with the etiology of AIS. METHODS: Twenty cases with average age of
      (15.1 +/- 2.2) years and average Cobb angle of 56 degrees +/- 16 degrees ,
      including 10 cases with Cobb angle > 50 degrees and 10 cases with Cobb angle <or=
      50 degrees , were in AIS group. The apical vertebrae were from T(6 - 11). Twelve
      cases with average age of (11.6 +/- 3.2) years and average Cobb angle of 59
      degrees +/- 33 degrees were in congenital scoliosis (CS) group. The apical
      vertebrae were from T(7 - 12). Ten cases without scoliosis were in control group.
      The mRNA expression of melatonin receptor subtype MT1 and MT2 were detected by RT
      PCR method. RESULTS: The MT2 mRNA expression of paravertebral muscles on concave
      side was higher than that on convex side in AIS and CS groups (P < 0.05), but the
      MT1 mRNA expression showed no significant difference (P > 0.05). In AIS group,
      the ratio of MT2 mRNA expression on concave side compared with convex side in
      cases with Cobb angle > 50 degrees and cases with Cobb angle <or= 50 degrees
      showed no significant difference (P > 0.05). The MT1 and MT2 mRNA expression
      showed no significant difference in control group (P > 0.05). CONCLUSIONS: The
      melatonin receptor expression in bilateral paravertebral muscles in AIS is
      asymmetric, which may be a secondary change and has no important role in the
      pathogenesis of AIS.

PMID- 16889731
TI  - [Percutaneous reduction and fixation of osteoporotic fractures for the proximal
      humerus in a geriatric population].
AB  - OBJECTIVE: To appraise the value of clinical treatment of percutaneous reduction
      and fixation of osteoporotic fractures for the proximal humerus in a geriatric
      population. METHODS: Postoperation complication, mortality in hospital and within
      the first three months postoperation, operation time, blood transfusion
      requirement, the functional outcome of the shoulder had been analysed and
      observed in 37 cases for open and closed fixation. RESULTS: Closed reduction
      provided the benefit of obtaining and holding adequate reduction without the soft
      tissue dissection of open reduction and internal fixation. The general
      complication and mortality in the first three months postoperation in the open
      reduction and internal fixation cases were more severe than the percutaneous
      cases. CONCLUSIONS: Open operation increases the risk of the geriatric population
      with osteoporotic proximal humerus fracture; percutaneous reduction and fixation
      may be preferable.

PMID- 16889732
TI  - [Arthroscopic assisted diagnosis and treatment of knee extension limitation].
AB  - OBJECTIVE: To figure out the incidence and etiology of knee extension limitation
      and then to find out the proper methods of arthroscopic assisted diagnosis and
      treatment. METHODS: We reviewed 303 cases of arthroscopic assisted operation from
      January to October 2003, 95 cases of which suffered from knee extension
      limitation before operation, including 54 male and 41female and the mean age was
      36.2 years old. The direct reasons of knee extension limitation were identified
      by routine arthroscopic examination and operations were carried out according to
      results of the examination. RESULTS: Incidence of knee extension limitation in
      this group of patients was 31.4%. Trauma, mainly meniscus and ligament injury
      accounted for 67.4%, which was the most common reason of knee extension
      limitation. Acute or chronic arthritis like degenerative arthritis, non-specific
      synovitis, synovial chondromatosis, rheumatoid arthritis, pigmented villonodular
      synovitis, gouty arthritis and acute pyogenic arthritis formed another common
      reason. The follow-up period ranged from 3 to 20 months, average 13.3 months. 82
      cases gained full extension immediately after operation, 9 cases gained full
      extension after 3 weeks rehabilitation post-operation, 4 cases did not gain full
      extension 1 year after operation, recurrence was observed in 4 cases.
      CONCLUSIONS: Arthroscopy is the best method for diagnosis of knee extension
      limitation at present. Satisfactory results can be expected after early
      arthroscopic assisted treatment.

PMID- 16889733
TI  - [Total hip surface replacement arthroplasty: report of 31 cases].
AB  - OBJECTIVE: To introduce the technique of total hip surface replacement, evaluate
      the early results and review the factors which affect the results. METHODS: From
      October 2000 to January 2005, 31 patients (37 hips) with osteonecrosis,
      osteoarthritis, hip dysplasia, ankylosing spondylitis were treated with the total
      hip surface replacement. Among them, 15 were male, and 16 were female, with an
      average age of 42 years (range from 23 - 65 years). All the 31 patients had the
      indications for hip surface replacement. Standard operation technique which was
      brought forth by Amstutz and Nelson was employed, and all patients were followed
      up after operation. RESULTS: Patients were followed up for an average period of
      42 months (3 - 51 months). There were no femoral neck fracture, no dislocation,
      no infection in all patients. Radiolucent line existed around acetabular
      prosthesis in 1 hip and another hip had been revised because the prosthesis of
      femoral head was in incorrect situation. The average Harris hip score improved
      significantly from 30 to 90, and the score was 93 in the latest follow-up. Based
      on Harris system, 35 hips were excellent, 1 hip good, and 1 hip fail.
      CONCLUSIONS: The total hip surface replacement is an effective solution for the
      problem of the patients with osteonecrosis of the femoral head, osteoarthritis,
      hip dysplasia and ankylosing spondylitis. The short-term results are satisfied.

PMID- 16889737
TI  - [Lumbar interbody fusion using autologous bone marrow mesenchymal stem cell
      calcium phosphate ceramic composite in rhesus monkey].
AB  - OBJECTIVE: To determine the osteogenic capacity of autologous bone marrow
      mesenchymal stem cells (BMSCs)-calcium phosphate ceramic composites in vitro and
      implanted as a bone graft substitute for lumbar anterior interbody fusion in
      rhesus monkeys. METHODS: From March 2003 to April 2005, 9 adult rhesus monkeys
      underwent lumbar L(3 - 4) and L(5 - 6) discectomy and interbody fusion via an
      anterior retroperitoneal approach. Two fusion sites in each animal were randomly
      assigned to two of three treatments: autogenous tricortical iliac crest bone
      graft (autograft group, n = 6) or cell-free ceramic graft (ceramic group, n = 6)
      or BMSCs-ceramic composite graft (BMSCs group, n = 6). Autologous BMSCs were
      culture-expanded and stimulated with osteogenic supplement. The cell-ceramic
      composites were constructed in a rotary dynamic cell culture system. The spinal
      fusion segments were evaluated by radiography, biomechanical testing, histologic
      analysis and histomorphometric analysis at 3 months post-surgery. RESULTS:
      Biomechanical testing showed that spinal segments from the autograft group and
      the BMSCs-ceramic group were statistically and significantly stiffer than the
      cell-free ceramic group. The BMSCs-ceramic group and the autograft group showed
      equivalent biomechanical stiffness by statistical analysis. Histologically, both
      the autograft group and the BMSCs-ceramic group achieved osseous union, but the
      cell-free ceramic group had a fibrous union. Quantitative histologic analysis
      showed that the amount of bone formation was significantly greater in the
      autograft group and the BMSCs-ceramic group compared with the cell-free ceramic
      group. However, the amount of ceramic residue was significantly greater in the
      cell-free ceramic group versus the BMSCs-ceramic group. CONCLUSIONS: The results
      indicate that BMSC-ceramic composites can enhance bone regeneration and achieve
      osseous spinal fusion 3 months after the implantation in rhesus monkey interbody
      fusion model. Cell-free ceramics has an unsatisfactory efficacy in spinal fusion
      due to its tense fibrous fusion.

PMID- 16889738
TI  - [Biological characterization of rabbit's articular chondrocytes by confluent
      culture in vitro].
AB  - OBJECTIVE: To obtain large amount of differentiated chondrocytes in vitro,
      examine and compare the biological characterization of rabbits' articular
      chondrocyte cultured in different density in vitvo. METHODS: From November 2001
      to June 2004, articulate tissues were obtained from the joints of the adult
      rabbits. Chondrocytes were isolated from the cartilage tissue with type II
      collagenase digestion and cultured in DMEM/F-12 supplemented with 20% fetal
      bovine serum (FBS). The chondrocytes were cultured with low density of monolayer
      culture and high density of confluent culture respectively. The differentiated
      phenotype was evaluated by histochemistry or immunohistochemistry. RESULTS: When
      chondrocytes cultured in monolayer and in low density, it proliferated rapidly
      during the three generations, but with the same time, dedifferentiation was also
      rapid. After the third passage, most of the passage cells lost the phenotype, and
      the proliferation also stagnated. While chondrocytes cultured in high density,
      dedifferentiation slowed down. And even the phenotypes of the dedifferentiated
      chondrocyte which were cultured in low density could reduced partly by followed
      high density culture. CONCLUSIONS: Culture chondrocytes by high density in vitro
      can effectively maintain the differentiated phenotype of chondrocyte. It also
      keeps the proliferation character as monolayer culture. The dedifferentiated
      chondrocyte caused by many passages could redifferentiate partly. So it is
      indicated that confluent culture of original or expanded chondrocytes in high
      density is a better culture methods than culture in low density.

PMID- 16889739
TI  - [The effect of ultra high molecular weight polyethylene particles on macrophage].
AB  - OBJECTIVE: To study the effect of ultra high molecular weight polyethylene
      (UHMWPE) particles on macrophages and evaluate the expression of NFAT2, a key
      transcriptional factor for osteoclast differentiation. METHODS: From November
      2004 to February 2005, macrophages were co-cultured with UHMWPE particles. When
      observed at different times, the proliferation activity of macrophages was
      analyzed by MTT and the expression of calcineurin (CaN) and NFAT2 by
      immunohistochemical and RT-PCR method respectively. RESULTS: The macrophages
      phagocytosed UHMWPE particles in an early time, the expression of CaN and NFAT2
      was increased, while the proliferation activity was not enhanced. CONCLUSIONS:
      UHMWPE particles can stimulate macrophages to phagocytose significantly, and
      enhance the expression of the transcriptional factor NFAT2.

PMID- 16889743
TI  - Femtoliter compartment in liposomes for in vitro selection of proteins.
AB  - The aqueous compartment in liposomes provides a reaction resembling the cell and
      therefore is used as a microcompartment in which to study enzymatic reactions.
      However, regardless of their method of preparation, the heterogeneity in size of
      cell-size liposomes limits their potential uses. We established a strategy to
      estimate the internal aqueous volume of cell-size liposomes using a fluorescence
      activated cell sorter (FACS). Reactions inside individual liposomes can be
      measured in a high-throughput format provided that the encapsulated proteins give
      rise to a fluorescent signal such as by exhibiting fluorescence themselves or by
      catalyzing production of a fluorescent compound. The strategy of volume
      estimation was applied to in vitro selection experiments. The green fluorescent
      protein (GFP) gene was encapsulated into liposomes together with an in vitro
      translation system. Here liposomes carrying a single copy of the gene were
      identified using the internal aqueous volume information of individual liposomes,
      and those exhibiting higher green fluorescence intensity were sorted by the FACS
      machine. This system was able to enrich those encoding GFP with higher
      fluorescence intensity over those with lower intensity. These results suggest the
      possibility of performing evolutionary experiments in an environment that mimics
      the cell.

PMID- 16889744
TI  - Development of a coactivator displacement assay for the orphan receptor estrogen
      related receptor-gamma using time-resolved fluorescence resonance energy
      transfer.
AB  - The estrogen-related receptor-gamma (ERRgamma) is a constitutively active orphan
      receptor that belongs to the nuclear receptor superfamily and is most closely
      related to the estrogen receptors. Although its physiological ligand is unknown,
      ERRgamma has been shown to interact with synthetic estrogenic compounds such as 4
      hydroxytamoxifen (4-OHT), tamoxifen, and diethylstilbestrol (DES). To assess how
      coregulator proteins interact with ERRgamma in response to ligand, an in vitro
      interaction methodology using time-resolved fluorescence resonance energy
      transfer (TR-FRET) was developed using glutathione S-transferase (GST)-tagged
      ERRgamma ligand-binding domain (LBD), a terbium-labeled anti-GST antibody, a
      fluorescein-labeled peptide containing sequences derived from coregulator
      proteins, and various ligands. An initial screen of these coregulator peptides
      bearing the coactivator LXXLL motif, the corepressor LXXI/HIXXXI/L motif, or
      other interaction motifs from natural coactivator sequences or random phage
      display peptides indicated that the peptides PGC1alpha, D22, and SRC1-4, known as
      class III coregulators, interacted most strongly with ERRgamma in the absence of
      ligand. Given its assay window and biological relevance in energy metabolism and
      obesity, further studies were conducted with PGC1alpha. Fluorescein-labeled
      PGC1alpha peptide was displaced from the ERRgamma LBD in the presence of
      increasing concentrations of 4-OHT and tamoxifen, but DES was less effective in
      PGC1alpha displacement. The statistical parameter Z' factor that measures the
      robustness of the assay was greater than 0.8 for displacement of PGC1alpha from
      ERRgamma LBD in the presence of saturating 4-OHT over an assay incubation time of
      1-6 h, indicating an excellent assay. These findings also suggest that binding of
      4-OHT, tamoxifen, or DES to ERRgamma results in differential affinity of
      coregulators for ERRgamma due to unique ligand-induced conformations.

PMID- 16889745
TI  - Development and validation of a platelet calcium flux assay using a fluorescent
      imaging plate reader.
AB  - Calcium signaling in platelets is an important physiological response to various
      aggregation stimuli. Loading platelets with various fluorescent dyes and
      measuring the change in calcium concentration using a spectrofluorometer has been
      the traditional approach to studying calcium signaling. This method suffers from
      the need for large platelet samples and a decrease in total fluorescence signal
      with time due to photobleaching. Therefore, it is rarely used to measure the
      quantitative effect of an agonist or antagonist on calcium signaling. Adaptation
      of these measurements to a fluorescent imaging plate reader (FLIPR) format allows
      the sample size to be reduced by 5- to 10-fold, and the microplate format allows
      a significant increase in throughput. Addition of the agonists to all wells
      simultaneously serves to normalize the total response. This article describes the
      first use of a FLIPR to study the calcium flux in human platelets. The IC(50)
      values showed a linear correlation with the K(i) for receptor binding in washed
      platelets. The generality of the methodology was shown by measuring EC(50) values
      for agonists and IC(50) values for antagonists of the platelet G protein-coupled
      receptor P2Y(1) and for the ion channel P2X(1).

PMID- 16889746
TI  - Photodynamic therapy down-regulates the invasion promoting factors in human oral
      cancer.
AB  - Squamous cell carcinomas of the head and neck are characterized by their high
      tendency for invasion and metastasis. Several studies have identified the roles
      of matrix metalloproteinases (MMPs), vascular endothelial growth factors (VEGF)
      and urokinase plasminogen activators (uPA) in this process. Photodynamic Therapy
      (PDT) is an emerging treatment currently in clinical practice for the treatment
      of early cancer. Here we evaluate, in vitro, the influence of PDT on the
      expression of these molecules. A series of human keratinocyte cell lines derived
      from human oral squamous cell carcinomas (OSCC) were used as the PDT 'targets' in
      this study. Each cell line was subjected to sublethal dose of PDT. Activity of
      MMP-2, MMP-9, MMP-13, uPA and VEGF were evaluated at protein levels using
      zymography and ELISA on culture medium. For uPA, a chromogenic assay was
      performed. Gelatin zymography results revealed that, in control medium, MMP-9 and
      MMP-2 were secreted in proform. MMP-2 was highly expressed by H376 cells while
      VB6 and UP cells relatively show similar MMP-2 with comparatively low expression.
      For MMP-9, the latent type was highly expressed by VB6 cells and only slightly by
      H376, while active-MMP-9 was expressed by VB6 cell line only. Following PDT, both
      active and latent MMP-2 and MMP-9 were down regulated by UP and VB6 cells
      (p<0.001), while H376 showed an increase in active-MMP-2. These observations were
      supported by ELISA. This study has demonstrated that, PDT causes the suppression
      of factors responsible for tumour invasion which may be of therapeutic value.

PMID- 16889747
TI  - The self-assembly ability of the first microtubule-binding repeat from tau and
      its modulation by phosphorylation.
AB  - Aggregation of abnormally phosphorylated tau in the form of tangs of paired
      helical filaments (PHFs) is one of the hallmarks of Alzheimer's disease (AD) and
      other tauopathies. It is of fundamental importance to study the mechanism of PHF
      formation and its modulation by phosphorylation. In this work, we have focused on
      the first microtubule-binding repeat of tau encompassing an abnormal
      phosphorylation site Ser262. The assembly propensities of this repeat and its
      corresponding phosphorylated form were investigated by turbidity and electron
      microscopy. Additionally, conformation of the two peptides is also analyzed
      through circular dichroism (CD) and NMR spectroscopy. Our results reveal that
      both of them are capable of self-assembly and phosphorylation at Ser262 could
      speed up the process of assembly. A possible mechanism of PHF formation is
      proposed and enhancing effect of phosphorylation on assembly provides an
      explanation to its toxicity in Alzheimer's disease.

PMID- 16889748
TI  - Direct detection of glycogenin reaction products during glycogen initiation.
AB  - Glycogenin initiates glycogen synthesis in an autocatalytic reaction in which
      individual glucose residues are covalently linked to Tyrosine 194 in order to
      form a short priming chain of glucose residues that is a substrate for glycogen
      synthase which, combined with the branching enzyme, catalyzes the bulk synthesis
      of glycogen. We sought to develop a new enzymatic assay to better characterize
      both the chemical and enzymatic characteristics of this unusual reaction. By
      directly detecting the reaction products using electrospray mass spectrometry
      this procedure permits both the visualization of the intact individual reaction
      species produced as a function of time and quantitation of the levels of each of
      species. The quantitation of the reaction agrees well with previous measurements
      of both catalytic rate and the change in rate as a function of average
      glucosylation. The results from this assay provide new insight into the mechanism
      by which glycogenin catalyzes the initiation reaction.

PMID- 16889749
TI  - The involvement of the 67 kDa laminin receptor-mediated modulation of
      cytoskeleton in the degranulation inhibition induced by epigallocatechin-3-O
      gallate.
AB  - Recently, we have reported that (-)-epigallocatechin-3-O-gallate (EGCG) acts as
      an inhibitor of degranulation. However, the inhibitory mechanism for
      degranulation is still poorly understood. Here we show that suppression of
      exocytosis-related myosin II regulatory light chain phosphorylation and
      alteration of actin remodeling are involved in the inhibitory effect of EGCG on
      the calcium ionophore-induced degranulation from human basophilic KU812 cells.
      Surface plasmon resonance assay also revealed that EGCG binds to the cell
      surface, and the disruption of lipid rafts resulted in reduction of EGCG's
      ability. We have previously identified the raft-associated 67kDa laminin receptor
      (67LR) as an EGCG receptor on the cell surface. Treatment of the cells with anti
      67LR antibody or RNA interference-mediated downregulation of 67LR expression
      abolished the effects of EGCG. These findings suggest that EGCG-induced
      inhibition of the degranulation includes the primary binding of EGCG to the cell
      surface 67LR and subsequent modulation of cytoskeleton.

PMID- 16889751
TI  - Roles of the heme and heme ligands in the activation of CooA, the CO-sensing
      transcriptional activator.
AB  - CooA of Rhodospirillum rubrum is a CO-sensing, heme-containing transcriptional
      activator that regulates the expression of the genes responsible for CO
      oxidation. We randomized the codons for residues 75-77 of CooA which include two
      proximal heme ligands, screened for both CO-dependent and CO-independent
      variants, and characterized in vivo and in vitro properties of selected CooA
      variants. The analysis showed that small residues at position 75 are critical and
      that, as previously suspected, His77 is absolutely necessary for CO
      responsiveness of CooA. Many hemeless variants altered at those residues were
      found to be constitutively active. We propose that proximal heme pocket residues
      of wild-type CooA have important role in stabilizing both active and inactive
      heme positions for its CO-sensing function.

PMID- 16889750
TI  - Leukotriene B4 stimulates human monocyte-derived dendritic cell chemotaxis.
AB  - Although leukotriene B4 (LTB4) has been reported to stimulate monocytes and
      neutrophils, its role on dendritic cell (DC) activity has not been examined.
      Here, we investigated the expression of LTB4 receptor and the effect of LTB4 on
      human DC chemotaxis. We analyzed LTB4 receptors, BLT1 and BLT2, by using RT-PCR.
      DCs express BLT2 but not BLT1 mRNA. DCs were chemotactically migrated to LTB4.
      LTB4-induced DC chemotaxis was completely inhibited by pertussis toxin,
      indicating the role of Gi proteins. LTB4 induced mitogen activated protein kinase
      activation and Akt activation. LTB4-induced DC chemotaxis was mediated by
      extracellular signal-regulated protein kinase and phosphoinositide 3-kinase but
      not by p38 kinase. BLT2-selevite antagonist, LY255283, almost completely
      inhibited DC chemotaxis induced by LTB4 but not by Trp-Lys-Tyr-Met-Val-D-Met.
      Thus human myeloid DCs express functional BLT2 but not BLT1, suggesting a
      physiological role of LTB4 and BLT2 in regulating DC trafficking during induction
      of immune responses.

PMID- 16889752
TI  - Cell death induced by MPPa-PDT in prostate carcinoma in vitro and in vivo.
AB  - Lack of effective photosensitizers has become a major limit for extensive
      application of photodynamic therapy. In this study, the photocytotoxicity and
      mode of death induced by a newly developed photosensitizer MPPa, a derivative of
      chlorophyll a, were investigated in PC-3M cell line, a highly metastatic variant
      of poorly differentiated androgen-independent proctanec adenocarcinoma PC-3. MTT
      reduction assay was used to measure cytotoxicity in both PC-3M and HUVEC, after
      which a flow cytometer was used to measure apoptotic rate and cell cycle, and
      then Caspase-3, -8, -9 were investigated. Finally, an animal model was set up to
      embody the curative effect and for histopathological examinations. The
      photocytotoxicity of MPPa showed both light- and drug-dose dependent
      characteristics and no significant dark cytotoxicity was observed in PC-3M cells.
      In HUVEC, MPPa exhibited an obviously low cytotoxicity. By other in vitro
      studies, we found MPPa-PDT induced apoptotic mainly via the mitochondrial/Caspase
      9/Caspase-3 pathway and could restrain the cell cycle progression from the more
      sensitive G0/G1-phases. In vivo, the tumour growth was significantly inhibited
      after PDT, and many apoptotic cells could be seen by histopathological
      examinations. These results indicate the death way of cells induced by MPPa is
      mainly via mild apoptotic and the cure effect is obvious, suggesting that MPPa is
      a potential photosensitizer of photodynamic therapy for prostate cancer.

PMID- 16889753
TI  - K-Ras4B proteins are expressed in the nucleolus: Interaction with nucleolin.
AB  - Kirsten Ras4B (K-Ras4B) is a potent onco-protein that is expressed in the
      majority of human cell types and is frequently mutated in carcinomas. K-Ras4B,
      like other members of the Ras family of proteins, is considered to be a
      cytoplasmic protein that must be localized to the plasma membrane for activation.
      Here, using confocal microscopy and biochemical analysis, we show that K-Ras4B,
      but not H-Ras or the closely related K-Ras4A, is also present in the nucleoli of
      normal and transformed cells. Subcellular fractionation and immunostaining show
      that K-Ras4B is located not only in the cytoplasm, but also in the nucleolar
      compartment. Modification of a C-terminal hexa-lysine motif unique to K-Ras4B
      results in exclusively cytoplasmic forms of the protein. Nucleolin, a pleiotropic
      regulator of cellular processes, including transcriptional regulation, is also
      characterized by a nucleolar-like nuclear appearance. We show that K-Ras4B and
      nucleolin co-localize within the nucleus and that nucleolin physically associates
      with K-Ras4B. Inhibition of K-Ras4B/nucleolin association blocked nucleolar
      localization of K-Ras4B. Using siRNA to knockdown the expression of nucleolin
      eliminated the nucleolar localization of K-Ras4B and significantly repressed the
      activation of the well-characterized K-Ras4B transcriptional target Ap-1, but
      stimulated Elk1. These data provide evidence of a nucleolar localization of K
      Ras4B and describe a functional association between K-Ras4B and nucleolin.

PMID- 16889754
TI  - Gomisin A alters substrate interaction and reverses P-glycoprotein-mediated
      multidrug resistance in HepG2-DR cells.
AB  - Through an extensive herbal drug screening program, we found that gomisin A, a
      dibenzocyclooctadiene compound isolated from Schisandra chinensis, reversed
      multidrug resistance (MDR) in Pgp-overexpressing HepG2-DR cells. Gomisin A was
      relatively non-toxic but without altering Pgp expression, it restored the
      cytotoxic actions of anticancer drugs such as vinblastine and doxorubicin that
      are Pgp substrates but may act by different mechanisms. Several lines of evidence
      suggest that gomisin A alters Pgp-substrate interaction but itself is neither a
      Pgp substrate nor competitive inhibitor. (1) First unlike Pgp substrates gomisin
      A inhibited the basal Pgp-associated ATPase (Pgp-ATPase) activity. (2) The
      cytotoxicity of gomisin A was not affected by Pgp competitive inhibitors such as
      verapamil. (3) Gomisin A acted as an uncompetitive inhibitor for Pgp-ATPase
      activity stimulated by the transport substrates verapamil and progesterone. (4)
      On the inhibition of rhodamine-123 efflux the effects of gomisin A and the
      competitive inhibitor verapamil were additive, so were the effects of gomisin A
      and the ATPase inhibitor vanadate. (5) Binding of transport substrates with Pgp
      would result in a Pgp conformational change favoring UIC-2 antibody reactivity
      but gomisin A impeded UIC-2 binding. (6) Photocrosslinking of Pgp with its
      transport substrate [125I]iodoarylazidoprazosin was inhibited by gomisin A in a
      concentration-dependent manner. Taken together our results suggest that gomisin A
      may bind to Pgp simultaneously with substrates and alters Pgp-substrate
      interaction.

PMID- 16889755
TI  - The immunomodulator AS101 induces growth arrest and apoptosis in multiple
      myeloma: association with the Akt/survivin pathway.
AB  - Multiple Myeloma (MM) is a clonal B-cell malignancy affecting both the immune and
      the skeletal systems, and accounts for 10% of all hematological cancers. The
      immunomodulator ammonium trichloro (dioxoethylene-O,O') tellurate (AS101) is a
      non-toxic compound which has direct anti-tumoral properties in several tumor
      models. The present study examined the anti-tumoral activity of AS101 in MM by
      targeting the Akt/Survivin signaling pathway, crucial for survival. We showed
      that AS101 inhibites cell proliferation and colonies formation of MM cell lines,
      in a dose-dependent manner. AS101 induced G(2)/M growth arrest and increased both
      cyclin-dependent kinase inhibitor p21(waf1) protein levels and Cdk1 (p34(cdc2))
      inhibitory phosphorylation. Longer incubation of MM cells with AS101 resulted in
      accumulation of apoptotic cell population and in increased caspase 9, 3 and 7
      activities. We also showed that AS101 down-regulated Akt phosphorylation and
      decreased expression of the inhibitor of apoptosis, survivin. Since Akt and
      survivin are potentials targets for MM therapy, we suggest that AS101, currently
      being used in clinical studies, may have therapeutic implications in myeloma and
      other hematopoietic malignancies.

PMID- 16889756
TI  - Inflammation and cancer: how hot is the link?
AB  - Although inflammation has long been known as a localized protective reaction of
      tissue to irritation, injury, or infection, characterized by pain, redness,
      swelling, and sometimes loss of function, there has been a new realization about
      its role in a wide variety of diseases, including cancer. While acute
      inflammation is a part of the defense response, chronic inflammation can lead to
      cancer, diabetes, cardiovascular, pulmonary, and neurological diseases. Several
      pro-inflammatory gene products have been identified that mediate a critical role
      in suppression of apoptosis, proliferation, angiogenesis, invasion, and
      metastasis. Among these gene products are TNF and members of its superfamily, IL
      1alpha, IL-1beta, IL-6, IL-8, IL-18, chemokines, MMP-9, VEGF, COX-2, and 5-LOX.
      The expression of all these genes are mainly regulated by the transcription
      factor NF-kappaB, which is constitutively active in most tumors and is induced by
      carcinogens (such as cigarette smoke), tumor promoters, carcinogenic viral
      proteins (HIV-tat, HIV-nef, HIV-vpr, KHSV, EBV-LMP1, HTLV1-tax, HPV, HCV, and
      HBV), chemotherapeutic agents, and gamma-irradiation. These observations imply
      that anti-inflammatory agents that suppress NF-kappaB or NF-kappaB-regulated
      products should have a potential in both the prevention and treatment of cancer.
      The current review describes in detail the critical link between inflammation and
      cancer.

PMID- 16889757
TI  - Mifepristone versus placebo in the treatment of psychosis in patients with
      psychotic major depression.
AB  - BACKGROUND: Abnormalities in the hypothalamic pituitary adrenal axis have been
      implicated in the pathophysiology of psychotic major depression (PMD). Recent
      studies have suggested that the antiglucocorticoid, mifepristone might have a
      role in the treatment of PMD. The current study tested the efficacy of
      mifepristone treatment of the psychotic symptoms of PMD. METHODS: 221 patients,
      aged 19 to 75 years, who met DSM-IV and SCID criteria for PMD and were not
      receiving antidepressants or antipsychotics, participated in a double blind,
      randomized, placebo controlled study. Patients were randomly assigned to either 7
      days of mifepristone (n = 105) or placebo (n = 116) followed by 21 days of usual
      treatment. RESULTS: Patients treated with mifepristone were significantly more
      likely to achieve response, defined as a 30% reduction in the Brief Psychiatric
      Rating Scale (BPRS). In addition, mifepristone treated patients were
      significantly more likely to achieve a 50% reduction in the BPRS Positive Symptom
      Scale (PSS). No significant differences were observed on measures of depression.
      CONCLUSION: A seven day course of mifepristone followed by usual treatment
      appears to be effective and well tolerated in the treatment of psychosis in PMD.
      This study suggests that the antiglucocorticoid, mifepristone, might represent an
      alternative to traditional treatments of psychosis in psychotic depression.

PMID- 16889758
TI  - Behavioral stress and activated serotonergic neurotransmission induce XBP-1
      splicing in the rat brain.
AB  - The splicing of 26 nucleotides in the coding region of the X-box binding protein
      1 (XBP-1) transcript to generate a mature active transcription factor is a part
      of the unfolded protein response to intracellular endoplasmic reticulum stress.
      In this study, we demonstrated that XBP-1 splicing is promptly induced in the rat
      brain including the hippocampus by both inescapable electric foot shock (IS) and
      pharmacologically manipulated activation of 5-hydroxytryptamine release in a dose
      dependent manner. By administering ketanserin, a 5-hydroxytryptamine 2A
      antagonist, however, we could only partially block the increased splicing by IS
      and observed that the splicing was not influenced by lithium carbonate
      pretreatment. Although it is still unclear whether the enhanced unfolded protein
      response functions neuroprotectively by modulating the rate of general
      translation and increasing chaperone proteins or whether it eventually induces
      cellular damage by triggering apoptosis, the present results indicate the
      possible existence of a new adaptive intracellular signaling pathway in the brain
      that responds to environmentally challenged behavioral stress loading.

PMID- 16889760
TI  - Mitochondrial involvement in drug-induced hepatic injury.
AB  - Hepatic injury remains not only the commonest reason for the termination of drugs
      in their pre-clinical development but is also the most frequent reason for the
      withdrawal of approved drugs from the market. Mitochondria are the central point
      where the different signals responsible for initiating hepatocyte cell death
      converge, irrespective of whether the cells ultimately die by apoptosis, necrosis
      (oncosis) or autophagic cell death. These signals can be in the form of direct
      damage to the mitochondria leading to permeability transition or can act
      indirectly through activation of death receptors and downstream pro-apoptotic Bcl
      2 family proteins. This paper reviews our current knowledge about how hepatotoxic
      drugs, whether direct acting or through induction of steatosis or cholestasis,
      target mitochondria and cause hepatic injury.

PMID- 16889759
TI  - Association of caffeine to MDMA does not increase antinociception but potentiates
      adverse effects of this recreational drug.
AB  - Ecstasy (MDMA) street tablets often contain several other compounds in addition
      to MDMA, particularly caffeine. Then, it becomes necessary to study the
      consequences of caffeine plus MDMA combination. MDMA (1 mg/kg) elicited an
      analgesic response both at the spinal and supraspinal levels. However, when
      associated, MDMA and caffeine did not show any synergistic interaction. When
      caffeine was administered prior to MDMA, a potentiation of locomotor activity was
      observed, which consisted in an increase in maximal values and in a prolonged
      time of activity. In the neurotoxicity studies, a hyperthermic effect of MDMA was
      observed. Although caffeine alone failed to alter body temperature, it
      potentiated MDMA-induced hyperthermia. This association also significantly
      increased MDMA lethality (from 22% to 34%). Following administration of MDMA to
      rats, there was a persistent decrease in the number of serotonin transporter
      sites in the cortex, striatum and hippocampus, which was potentiated by caffeine
      co-treatment. This MDMA toxicity in rats was accompanied by a transient
      dopaminergic impairment in the striatum, measured as decreased [(3)H]WIN35428
      binding sites, by 31% 3 days after treatment, which was not modified by caffeine.
      A transient down-regulation of 5-HT(2) receptors occurred in the cortex of MDMA
      treated rats, whose recovery was slowed by co-treatment with caffeine. In
      conclusion, the association of MDMA with caffeine does not generate any
      beneficial effects at the antinociceptive level. The acute effects stemming from
      this association, in tandem with the final potentiation of serotonergic terminals
      injury, provide evidence of the potentially greater long-term adverse effects of
      this particular recreational drug combination.

PMID- 16889761
TI  - Ascorbic acid and alpha-tocopherol protect anticancer drug cisplatin induced
      nephrotoxicity in mice: a comparative study.
AB  - BACKGROUND: Oxidative stress, resulting from an imbalance between prooxidant and
      antioxidant systems in favor of the former, largely contributes to immune system
      deregulation and complications observed in end-stage renal disease (ESRD) and
      patients treated with hemodialysis. Reactive oxygen species and free radicals are
      involved in the nephrotoxicity induced by a synthetic anticancer drug cisplatin.
      METHODS: A comparative study on the nephroprotective effects of antioxidant
      vitamins (250 and 500 mg/kg, p.o.), vitamin C (ascorbic acid) and vitamin E
      (alpha-tocopherol), was evaluated using cisplatin (10 mg/kg body wt, i.p.)
      induced oxidative renal damage in mice. Urea and creatinine in serum were
      estimated for the renal function. Antioxidant status was estimated in kidney
      homogenate. RESULTS: We found that both vitamins at 500 mg/kg significantly
      (P<0.01) protected the nephrotoxicity induced by cisplatin. The cisplatin induced
      increase of urea and creatinine concentrations were reduced in the vitamins plus
      cisplatin (250 and 500 mg/kg, p.o.)-treated groups. However the cisplatin induced
      decline of renal antioxidant enzymes such as superoxide dismutase (SOD), catalase
      (CAT), glutathione peroxidase (GPx) activities were increased only in the 500
      mg/kg vitamins treated groups. Both vitamins at 250 and 500 mg/kg could increase
      the concentration of reduced glutathione (GSH) and protected the increase of
      cisplatin induced lipid peroxidation. CONCLUSIONS: Higher doses of vitamins are
      effective to protect oxidative renal damage and vitamin C is the better
      nephroprotective agent than vitamin E. The protection is mediated partially by
      preventing the decline of renal antioxidant status.

PMID- 16889763
TI  - Identification of over-expressed proteins in oral squamous cell carcinoma (OSCC)
      patients by clinical proteomic analysis.
AB  - BACKGROUND: Oral cancer is a worldwide problem. It is a universal aggressive
      disease in the population of smoking and drinking. The oral cancer mortality has
      been ranked 5th place in Taiwan in male cancer patients. A number of protein
      markers for oral cancer are still not applicable in large populations. Proteomic
      technologies provide excellent tools for rapid screening of a large number of
      potential biomarkers in malignant cells. METHOD: Proteomics and real-time
      quantitative RT-PCR were used to analyze over-expressed proteins in 10 OSCC
      patients. RESULT: Forty-one proteins were identified as commonly over-expressed
      in OSCC tissues. In OSCC tissues, alphaB-crystallin, tropomyosin 2, myosin light
      chain 1, heat shock protein 27 (HSP27), stratifin, thioredoxin-dependent peroxide
      reductase, flavin reductase, vimentin, rho GDP-dissociation inhibitor 2 (rho GDI
      2), glutathione S-transferase Pi (GST-pi) and superoxide dismutase [Mn] (MnSOD)
      were significantly over-expressed (an average of 7.2, 6.0, 5.7, 4.3, 3.6, 3.4,
      3.0, 3.0, 2.6, 2.5, 2.1-fold, respectively). In real-time quantitative RT-PCR
      analysis, the gene expressions of alphaB-crystallin, HSP27 and MnSOD were also
      increased in the cancer tissues, consistent with proteomic results. CONCLUSION:
      The identified proteins in this experiment may be used in future studies of
      carcinogenesis or as diagnostic markers and therapeutic targets for OSCC.

PMID- 16889762
TI  - Evidence of oxidative and nitrosative stress in patients with cervical squamous
      cell carcinoma.
AB  - BACKGROUND: We conducted a study to evaluate reactive oxygen species (ROS) and
      reactive nitrogen species (RNS) simultaneously together with the antioxidant
      status in patients with cervical carcinoma. METHODS: We measured lipid
      peroxidation product, including malondialdehye (MDA), nitric oxide (NO) products,
      including nitrite (NO(2)(-)), nitrate (NO(3)(-)) and total nitrite (TNO(2)(-))
      and antioxidant enzymes in 45 patients with cervical cancer and compared them
      against 30 healthy controls. RESULTS: Plasma as well as erythrocyte MDA and
      plasma NO levels was higher (p<0.001) in cervical cancer as compared to healthy
      controls. Antioxidant enzymes, Superoxide dismutase (SOD), catalase (CAT) and
      glutathione peroxidase (GPx) activities, were decreased (p<0.001) whereas
      glutathione S-transferase (GST) activity was increased (p<0.001) in cervical
      cancer patients. Lipid peroxidation and NO products accumulation correlated
      significantly with a deranged antioxidant system. CONCLUSIONS: We demonstrated a
      possible involvement of both oxidative and nitrosative stress, as evidenced by
      increased lipid peroxidation and NO levels with altered antioxidant defense
      system in the pathogenesis of cervical cancer.

PMID- 16889764
TI  - An investigation into the similarities and differences governing the
      cryopreservation success of koala (Phascolarctos cinereus: goldfuss) and common
      wombat (Vombatus ursinus: shaw) spermatozoa.
AB  - The aim of this study was to determine the relative cryopreservation success of
      koala and wombat spermatozoa and to investigate reasons for their respective post
      thaw survival by examining the sperm's response to a range of osmotic media and
      determining the presence and distribution of F-actin. An hypothesis was proposed
      that F-actin may be imparting a degree of structural inflexibility to the koala
      sperm plasma membrane; hence, exposure of spermatozoa to cytochalasin D (5
      microM), a F-actin depolymerisation agent, should result in increased
      plasticisation of the membrane and greater tolerance of cell volume changes that
      typically occur during cryopreservation. In experiment 1, koala (n = 4) and
      wombat (n = 4) spermatozoa packaged in 0.25 mL straws were cryopreserved using
      two freezing rates (fast-3 cm above liquid N2 interface; slow-6 degrees C/min in
      a freezing chamber) and two glycerol concentrations (8 and 14% v/v) in a tris
      citrate glucose buffer with 15% (v/v) egg yolk. Wombat spermatozoa showed better
      (P < 0.01) post-thaw survival (% motile, % intact plasma membranes, % decondensed
      sperm heads) than koala spermatozoa. When exposed to media of varying osmolality,
      koala spermatozoa were less tolerant (% intact plasma membrane) of hyper-osmotic
      conditions (920 and 1410 mOsmol/kg) than wombat spermatozoa. F-actin was
      localised using a monoclonal antibody but only found in the wombat sperm head.
      When koala and wombat spermatozoa were exposed to media of varying osmolality,
      cytochalasin D had no beneficial effect on sperm survival (% intact plasma
      membranes). This study has demonstrated that wombat spermatozoa are highly
      tolerant of cryopreservation when compared to koala sperm but that spermatozoa
      from both species show greatest post-thaw survival when frozen slowly in 14%
      glycerol. Koala sperm are also particularly susceptible to hyper-osmotic
      environments but lack of detectable F-actin in the koala spermatozoan suggests
      that poor cryopreservation success in this species is unlikely to be associated
      with F-actin induced plasma membrane inflexibility.

PMID- 16889765
TI  - The effect of EGF and the comitogen, norepinephrine, on the proliferative
      responses of fresh and cryopreserved rat and mouse hepatocytes.
AB  - The effect of cryopreservation on the proliferative response of fresh and
      cryopreserved (CP) rat and mouse hepatocytes was studied. Of the parameters
      measured, incorporation of 3H-thymidine and bromodeoxyuridine (BdrU)
      incorporation were the most sensitive and LDH content was the least sensitive.
      The optimal seeding density for epidermal growth factor (EGF)-stimulated
      proliferative response in fresh rat and mouse hepatocytes was 1.8 x 10(4)
      cells/cm2 and 2.1 x 10(4) cells/cm2, respectively. 3H-thymidine incorporation by
      fresh rat and mouse hepatocytes was maximal in cultures treated with 10 and 5
      ng/ml EGF, respectively. The cell attachment of fresh rat hepatocytes after 48 h
      was higher (68%) than CP (42%), therefore, the CP hepatocyte seeding density was
      increased to 7.1 x 10(4) cells/cm2 so that the cell number after 48 h was the
      same as fresh hepatocytes. Using the adjusted seeding density, the 3H-thymidine
      and BdrU incorporation into fresh and CP rat hepatocytes was equivalent. The
      attachment efficiencies of fresh and CP mouse hepatocytes were the same,
      therefore, no adjustment was needed. The proliferative response (3H-thymidine
      incorporation and DNA content) to EGF was the same in fresh and CP mouse
      hepatocytes. The comitogen, norepinephrine (NE), increased the proliferative
      response to EGF to the same extent in both fresh and CP rat hepatocytes. In
      summary, cryopreserved rat and mouse hepatocytes retain their ability to
      proliferate in culture. Adjustment and monitoring of the seeding density is of
      high importance, especially with rat hepatocytes, which lose some attachment
      capacity after cryopreservation. The secondary mitogenic effect of NE is also
      retained by cryopreserved rat hepatocytes, suggesting that these cells retain
      alpha1-receptor function.

PMID- 16889766
TI  - Ras signaling is essential for lens cell proliferation and lens growth during
      development.
AB  - The vertebrate ocular lens is a simple and continuously growing tissue. Growth
      factor-mediated receptor tyrosine kinases (RTKs) are believed to be required for
      lens cell proliferation, differentiation and survival. The signaling pathways
      downstream of the RTKs remain to be elucidated. Here, we demonstrate the
      important role of Ras in lens development by expressing a dominant-negative form
      of Ras (dn-Ras) in the lens of transgenic mice. We show that lens in the
      transgenic mice was smaller and lens growth was severely inhibited as compared to
      the wild-type lens. However, the lens shape, polarity and transparency appeared
      normal in the transgenic mice. Further analysis showed that cell proliferation is
      inhibited in the dn-Ras lens. For example, the percentage of 5-bromo-2'
      deoxyuridine (BrdU)-labeled cells in epithelial layer was about 2- to 3-fold
      lower in the transgenic lens than in the wild-type lens, implying that Ras
      activity is required for normal cell proliferation during lens development. We
      also found a small number of apoptotic cells in both epithelial and fiber
      compartment of the transgenic lens, suggesting that Ras also plays a role in cell
      survival. Interestingly, although there was a delay in primary fiber cell
      differentiation, secondary fiber cell differentiation was not significantly
      affected in the transgenic mice. For example, the expression of beta- and gamma
      crystallins, the marker proteins for fiber differentiation, was not changed in
      the transgenic mice. Biochemical analysis indicated that ERK activity, but not
      Akt activity, was significantly reduced in the dn-Ras transgenic lenses. Overall,
      our data imply that the RTK-Ras-ERK signaling pathway is essential for cell
      proliferation and, to a lesser extent, for cell survival, but not for crystallin
      gene expression during fiber differentiation. Thus, some of the fiber
      differentiation processes are likely mediated by RTK-dependent but Ras
      independent pathways.

PMID- 16889767
TI  - Airborne particulate matter: Ionic species role in different Italian sites.
AB  - Epidemiological studies have provided evidences for an association between
      exposure to elevated levels of ambient particulate matter (PM) and increased
      mortality and morbidity. However, the exact physiochemical nature of the
      responsible component is not clear. Secondary airborne PM formed from gas-phase
      pollutants contributes significantly to the most severe particulate air quality
      events. Although chemical formation for ionic species of aerosol have been
      observed, they have not been well reported for local variation. This work
      evaluates the amount of secondary particulate ionic species: sulfates (SO(4)(2-))
      and nitrates (NO(3)(-)), chlorides (Cl(-)) and the mutagenic activities of PM10
      extracts in different Italian sites (one Southern, one Central and three
      Northern; in one of the latter also PM2.5 has been evaluated). In general, mean
      secondary species concentration constitutes about 35-45% of PM10 mass in the
      North sites, 15% in the center site and 20% in the South site and it is
      positively associated with PM10 levels. There are significant local differences
      in the mean levels of PM10 ionic constituents: NO(3)(-) are predominant in
      northern cities, SO(4)(2-) are more equally distributed and coastal southern city
      is abundant in Cl(-). Samples were also tested for mutagenicity with Salmonella
      typhimurium strains TA98 and TA100, with and without metabolic activation;
      mutagenicity did not correlate with PM10 concentrations. The results showed the
      important roles and the geographical variability of PM secondary species in the
      total mass PM10 concentrations and the usefulness of this biological approach for
      monitoring PM to understand hazards from PM.

PMID- 16889768
TI  - Exposure of young men to organochlorine pesticides in Southern Spain.
AB  - It has been hypothesized that endocrine disruptors and especially synthetic
      estrogenic environmental contaminants (xenoestrogens) are etiologic factors in
      the global decrease of sperm counts and other problems of the male reproductive
      tract, including cryptorchidism, hypospadias, and testicular cancer. This
      possibility has prompted research into the current and historical incidence of
      these diseases. The largest area of intensive greenhouse agriculture in Europe is
      near the Mediterranean coast of Southern Spain, where this activity has greatly
      expanded since the 1960s. We determined and compared levels of 14 organochlorine
      pesticides in the blood of 220 young males in Southern Spain. Aldrin, dieldrin,
      endrin, lindane, methoxychlor, endosulfans, and DDT and its metabolites were
      identified. Detectable concentrations of p,p'-DDE were found in 96% of serum
      samples. Among the remaining DDTs, o,p'-DDD was the most prevalent, detected in
      65% of serum samples. Detectable concentrations of endosulfan I or II or their
      metabolites endosulfan-diol, or -sulfate were found in all samples; endosulfan
      diol was the most frequently detected metabolite (92%) followed by sulfate.
      Results indicate that men of reproductive age in Southern Spain have been and are
      exposed to organochlorine pesticides. Because many of these chemicals have
      estrogenic and anti-androgenic activity, further research is warranted to
      interpret the male reproductive health consequences of this exposure.

PMID- 16889769
TI  - Kinins and neuroinflammation: dual effect on prostaglandin synthesis.
AB  - The role of kinins, well known as peripheral inflammatory mediators, in the
      modulation of brain inflammation is unclear. The present data show that
      bradykinin, a bradykinin B(2) receptor agonist, enhanced both basal and
      lipopolysaccharide-induced prostaglandin E(2) synthesis in rat neonatal glial
      cells in culture. By contrast, Lys-des-Arg(9)-bradykinin, which is a kinin
      breakdown product and a selective bradykinin B(1) receptor agonist, attenuated
      both basal and lipopolysaccharide-induced production of prostaglandin E(2) in
      glia. These results suggest a feedback regulatory mechanism of kinins on glial
      cells, in which prostaglandin synthesis is initially enhanced by bradykinin
      (B(2)) and eventually blocked by the effect of the kinin breakdown product,
      acting on bradykinin B(1) receptors.

PMID- 16889770
TI  - Osteopontin is associated with nuclear factor kappaB gene expression during tail
      suspension-induced bone loss.
AB  - Osteoporosis due to unloading-induced bone loss is a critical issue in the modern
      aging society. Although the mechanisms underlying this phenomenon are largely
      unknown, osteopontin (OPN) is one of the critical mediators required for
      unloading-induced bone loss [M. Ishijima, S.R. Rittling, T. Yamashita, K. Tsuji,
      H. Kurosawa, A. Nifuji, D.T. Denhardt, and M. Noda, Enhancement of osteoclastic
      bone resorption and suppression of osteoblastic bone formation in response to
      reduced mechanical stress do not occur in the absence of osteopontin, J Exp Med,
      193 (2001) 399-404]. To clarify the molecular bases for OPN actions, we carried
      out microarray analyses on the genes expressed in the femoral bone marrow cells
      in wild type and OPN-/- mice. The removal of the mechanical load induced bone
      loss in wild type, but not in OPN-/- mice, as previously reported. Expression
      analysis of 9586 cDNAs on a microarray system revealed that OPN deficiency
      blocked tail-suspension-induced expression of ten genes (group A). This
      observation was confirmed based on semi-quantitative RT-PCR analyses. On the
      other hand, expression of four genes (group B) was not altered by tail suspension
      in wild type but was enhanced in OPN-deficient mice. NF-kappaB p105 subunit gene
      (Nfkb1) was found in group A and Bax in group B. p53 gene expression was
      upregulated by tail suspension in wild type mice, but it was no longer observed
      in OPN-/- mice. These data indicate that OPN acts to mediate mechanical stress
      signaling upstream to the genes encoding apoptosis-related molecules, and its
      action is associated with alteration of the genes.

PMID- 16889771
TI  - A partial GDNF depletion leads to earlier age-related deterioration of motor
      function and tyrosine hydroxylase expression in the substantia nigra.
AB  - Glial cell line-derived neurotrophic factor (GDNF) is a trophic factor for
      peripheral organs, spinal cord, and midbrain dopamine (DA) neurons. Levels of
      GDNF deteriorate in the substantia nigra in Parkinson's disease (PD). A
      heterozygous mouse model was created to assess whether chronic reductions in this
      neurotrophic factor impact motor function and the nigrostriatal dopamine system
      during the aging process. Due to the important role GDNF plays in kidney
      development, kidney function and histology were assessed and were found to be
      normal in both wild-type (WT) and GDNF+/- mice up to 22 months of age. Further,
      the animals of both genotypes had similar weights throughout the experiment.
      Locomotor activity was assessed for male WT and GDNF+/- mice at 4-month intervals
      from 4 to 20 months of age. Both GDNF+/- and WT mice exhibited an age-related
      decline in horizontal activity, although this was found 4 months earlier in
      GDNF+/- mice, at 12 months of age. Comparison of young (8 month old) and aged (20
      month old) GDNF+/- and WT mice on an accelerating rotarod apparatus established a
      deficiency for aged but not young GDNF+/- mice, while aged WT mice performed as
      well as young WT mice on this task. Finally, both WT and GDNF+/- mice exhibited
      an age-related decrease in substantia nigra TH immunostaining, which was
      accelerated in the GDNF+/- mice. These behavioral and histological alterations
      suggest that GDNF may be an important factor for maintenance of motor
      coordination and spontaneous activity as well as DA neuronal function during
      aging, and further suggest that GDNF+/- mice may serve as a model for
      neuroprotective or rescue studies.

PMID- 16889772
TI  - High annealing temperature-random amplified polymorphic DNA (HAT-RAPD) analysis
      of three paramphistome flukes from Thailand.
AB  - The rumen flukes of 37 cows (Bos indicus) from Chiang Mai and Lamphun provinces
      were investigated, and the overall prevalence of infection was 78.38% (29/37).
      Three species were found: Paramphistomum epiclitum, Orthocoelium streptocoelium,
      and Fischoederius elongatus with prevalences of infection of 75.68%, 48.65%, and
      40.54%, respectively. Genomic DNA was amplified by polymerase chain reaction
      based on the high annealing temperature-random amplification of polymorphic DNA
      (HAT-RAPD) technique. Five random 10-mer oligonucleotide primers (OPA2, OPA4,
      OPB18, OPC9, and OPH11) produced distinct banding patterns in three species. No
      genetic variations in these three species were identified using 10 arbitary
      primers.

PMID- 16889773
TI  - Toxoplasma gondii: comparison of human CD34+ and monocyte-derived dendritic cells
      after parasite infection.
AB  - Human dendritic cells (DC) obtained in vitro from CD34(+) progenitors (CD34-DC)
      or blood monocytes (mo-DC) are different DC which may be used in a model of T.
      gondii infection. We compared the survival, infection rate and cell surface
      receptor expression of both DC types after living T. gondii tachyzoite infection.
      CD34-DC appeared less resistant to the parasite than mo-DC. At 48h post
      infection, chemokine receptors responsible for DC homing and migration were
      absent in mo-DC, while down regulation of CCR6 and up regulation of CCR7 was
      observed in CD34-DC. This result, suggesting migration ability of CD34-DC, was
      confirmed by in vitro migration experiments against different chemokines.
      Tachyzoite supernatant, used as chemokine, attracted immature CD34-DC as observed
      by MIP3alpha, while MIP3beta, as expected, attracted mature CD34-DC. Under
      similar conditions, no significant difference was noticed between mature or
      immature mo-DC. These data indicated that CD34-DC represent an alternative model
      that allows migration assay of infected DC by T. gondii.

PMID- 16889774
TI  - Neospora caninum: high susceptibility to the parasite in C57BL/10ScCr mice.
AB  - C57BL/10ScCr mice, lack Toll-like receptor 4 and a functional Interleukin-12
      receptor. Taking this into account, susceptibility of these mice to Neospora
      caninum infection was assessed comparatively to that of immunocompetent
      C57BL/10ScSn mice. C57BL/10ScCr mice inoculated intraperitoneally with 5x10(5)N.
      caninum tachyzoites showed a high susceptibility to this parasite. All infected
      C57BL/10ScCr mice were dead by day 8 post-infection whereas all control
      C57BL/10ScSn mice survived this parasitic challenge. Immunohistochemical analysis
      of infected C57BL/10ScCr mice showed N. caninum tachyzoites spread in the
      pancreas, liver, lung, intestine, heart and brain whereas no parasites were
      detected in similarly infected C57BL/10ScSn controls. The higher susceptibility
      of C57BL/10ScCr mice to neosporosis correlates with reduced interferon-gamma mRNA
      expression and increased IL-4 mRNA expression, comparatively to C57BL/10ScSn
      controls, detected in the spleen after the parasitic challenge. C57BL/10ScCr mice
      could thus be used as a new experimental model where to study immunobiological
      mechanisms associated with host susceptibility to neosporosis.

PMID- 16889775
TI  - Differential induction of electrophile-responsive element-regulated genes by n-3
      and n-6 polyunsaturated fatty acids.
AB  - In this study the n-3 polyunsaturated fatty acids (PUFAs) eicosapentaenoic acid
      and docosahexaenoic acid appear to be effective inducers of electrophile
      responsive element (EpRE) regulated genes, whereas the n-6 PUFA arachidonic acid
      is not. These n-3 PUFAs need to be oxidized to induce EpRE-regulated gene
      expression, as the antioxidant vitamin E can partially inhibit the PUFA induced
      dose-dependent effect. Results were obtained using a reporter gene assay, real
      time RT-PCR and enzyme activity assays. The induction of EpRE-regulated phase II
      genes by n-3 PUFAs may be a major pathway by which n-3 PUFAs, in contrast to n-6
      PUFAs, are chemopreventive and anticarcinogenic.

PMID- 16889776
TI  - The length of perimenopausal menstrual cycles increases later and to a greater
      degree than previously reported.
AB  - OBJECTIVE: To demonstrate that the perimenopausal increase in menstrual cycle
      length presented by Treloar et al. was biased by misidentified menopause dates,
      mean values classified by calendar year, and exclusion of menstrual cycles
      straddling two calendar years; and to use the revised data to investigate women's
      experiences of longer perimenopausal cycles. DESIGN: Secondary analysis of
      prospectively collected menstrual cycle data. SETTING: Center for Population and
      Health, Georgetown University. PATIENT(S): One hundred twenty white, college
      educated, US women in the Tremin Research Program on Women's Health.
      INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Mean cycle length and time spent
      in >40-day cycles, by year before menopause. RESULT(S): Mean estimates for each
      of the 4 years before menopause were 30.48, 35.02, 45.15, and 80.22 days,
      respectively, compared with the original analysis: 33.60, 43.91, 55.87, and 54.58
      days. In the year before menopause, the majority of women spent >or=75% of their
      time in cycles >40 days long. CONCLUSION(S): Treloar's estimates of mean cycle
      length were biased. Long cycles occurred throughout perimenopause, but the
      largest increase in mean cycle length did not occur until the final year before
      menopause. New estimates of the time spent in cycles >40 days may be useful
      clinically as well as epidemiologically for assessing menopausal onset and
      symptomatology.

PMID- 16889777
TI  - Immunohistochemical localization of serotonin (5-hydroxytryptamine) in the gonad
      and digestive gland of Mya arenaria (Mollusca: Bivalvia).
AB  - Serotonin (5-hydroxytryptamine or 5-HT) C(10)H(12)N(2)O plays a central role in
      several physiological processes in marine molluscs, especially in reproduction. 5
      HT acts as a neurohormone to modulate spawning, parturition and meiosis by
      reinitiating prophase in arrested oocytes. Preliminary experiments using 10(-5)M
      5-HT dissolved in aquarium water showed that 5-HT induced spawning movements in
      ripe clams and in both sexes of Mya arenaria while only a few males released
      sperm. The occurrence of serotoninergic fibers was demonstrated by PAP
      immunohistochemical reaction in the gonad of both sexes during gametogenesis. In
      an organism infected by the trematode parasite Prosorhynchus squamatus, we showed
      that serotoninergic innervation completely disappeared around the gonad's
      follicles. Although the gonad and digestive gland are intertwined, no
      serotoninergic innervations were found in the digestive gland. These findings
      suggest, for the first time to our knowledge in the soft shell clam, that
      serotonin might be involved in the regulation of gametogenesis.

PMID- 16889778
TI  - Odontometric systematic assessment of the Swartkrans SK 15 mandible.
AB  - This study reports a comparison of molar crown and cusp size and shape in the
      Swartkrans early Homo mandible SK 15 with relevant Plio-Pleistocene taxa.
      Univariate and multivariate methods are employed to consider the morphological
      affinities of this specimen and to assess its taxonomy. The case exists for
      classifying SK 15 in Homo habilis with 11 features aligning it with this species.
      The results of multivariate studies are consistent with this hypothesis.
      Moreover, SK 15 lacks a number of important features that characterise the
      mandibular molars of Homo sapiens erectus. Considerable evidence for parallelism
      in the dental morphology of SK 15 and H. habilis with A. robustus is discussed.
      Fossil evidence for the presence of H. sapiens erectus during the Plio
      Pleistocene of South Africa presently seems to be lacking. Archaeological
      interpretations should take greater account of this gap in the fossil record.

PMID- 16889780
TI  - Post-conception mating in wild long-tailed macaques (Macaca fascicularis):
      characterization, endocrine correlates and functional significance.
AB  - In many anthropoid primates, mating activity is not restricted to the ovarian
      cycle but also occurs during pregnancy. Although it has been suggested that the
      main function of this post-conception mating is to confuse paternity, studies
      showing whether or not male primates can distinguish between the fertile phase of
      the conception cycle (FPCC) and the period of peak post-conception mating (peak
      PCM) are almost non-existent. Here, we examine whether the pattern of female
      sexual traits (specific sexual behaviors, sexual swelling) and female
      attractiveness to males differ between FPCC and peak PCM in 6 wild female long
      tailed macaques. We also use fecal hormone analysis to investigate whether female
      traits during peak PCM are related to changes in female sex hormones. All females
      exhibited a distinct period of heightened mating activity around days 45-60 of
      gestation. During peak PCM, swelling size and frequency of female solicitations
      (but not reaching back) were significantly correlated with changes in the
      estrogen to progestogen ratio. Swelling size, frequency of female sexual
      behaviors and copulations and proportion of male-initiated copulations and
      ejaculations were not significantly different between FPCC and peak PCM. Although
      males spent significantly less time consorting females during peak PCM, all
      (particularly low-ranking and non-resident males) invested heavily in terms of
      reproductive costs associated with mate-guarding and mating during pregnancy. We
      conclude that post-conception mating in wild long-tailed macaques is not merely a
      by-product of endocrine changes and devoid of adaptive function. Our results more
      strongly support the hypothesis that it may form part of a female reproductive
      strategy to confuse paternity, which appears to apply particularly to low-ranking
      and extra-group males.

PMID- 16889781
TI  - Children facing a family member's acute illness: a review of intervention
      studies.
AB  - BACKGROUND: A review of psycho-educational intervention studies to benefit
      children adapting to a close (parent, sibling, or grandparent) family member's
      serious illness was conducted. OBJECTIVES: To review the literature on studies
      addressing this topic, critique research methods, describe clinical outcomes, and
      make recommendations for future research efforts. DATA SOURCES: Research
      citations from 1990 to 2005 from Medline, CINAHL, Health Source: Nursing/Academic
      Edition, PsycARTICLES, and PsycINFO databases were identified. REVIEW METHODS:
      Citations were reviewed and evaluated for sample, design, theoretical framework,
      intervention, threats to validity, and outcomes. Reviewed studies were limited to
      those that included statistical analysis to evaluate interventions and outcomes.
      RESULTS: Six studies were reviewed. Positive outcomes were reported for all of
      the interventional strategies used in the studies. Reviewed studies generally
      lacked a theoretical framework and a control group, were generally composed of
      small convenience samples, and primarily used non-tested investigator
      instruments. They were diverse in terms of intervention length and intensity, and
      measured short-term outcomes related to participant program satisfaction, rather
      than participant cognitive and behavioral change. CONCLUSIONS: The paucity of
      interventional studies and lack of systematic empirical precision to evaluate
      intervention effectiveness necessitates future studies that are methodologically
      rigorous.

PMID- 16889782
TI  - Understanding anthelmintic resistance: the need for genomics and genetics.
AB  - Anthelmintic resistance is a major problem for the control of many parasitic
      nematode species and has become a major constraint to livestock production in
      many parts of the world. In spite of its increasing importance, there is still a
      poor understanding of the molecular and genetic basis of resistance. It is
      unclear which mutations contribute most to the resistance phenotype and how
      resistance alleles arise, are selected and spread in parasite populations. The
      main strategy used to identify mutations responsible for anthelmintic resistance
      has been to undertake experimental studies on candidate genes. These genes have
      been chosen predominantly on the basis of our knowledge of drug mode-of-action
      and the identification of mutations that can confer resistance in model
      organisms. The application of these approaches to the analysis of benzimidazole
      and ivermectin resistance is reviewed and the reasons for their relative success
      or failure are discussed. The inherent limitation of candidate gene studies is
      that they rely on very specific and narrow assumptions about the likely identity
      of resistance-associated genes. In contrast, forward genetic and functional
      genomic approaches do not make such assumptions, as illustrated by the successful
      application of these techniques in the study of insecticide resistance. Although
      there is an urgent need to apply these powerful approaches to anthelmintic
      resistance research, the basic methodologies and resources are still lacking.
      However, these are now being developed for the trichostrongylid nematode
      Haemonchus contortus and the current progress and research priorities in this
      area are discussed.

PMID- 16889784
TI  - The chemical interpretation and practice of linear solvation energy relationships
      in chromatography.
AB  - This review focuses on the use of linear solvation energy relationships (LSERs)
      to understand the types and relative strength of the chemical interactions that
      control retention and selectivity in the various modes of chromatography ranging
      from gas chromatography to reversed phase and micellar electrokinetic capillary
      chromatography. The most recent, widely accepted symbolic representation of the
      LSER model, as proposed by Abraham, is given by the equation: SP=c + eE + sS + aA
      + bB + vV, in which, SP can be any free energy related property. In
      chromatography, SP is most often taken as logk' where k' is the retention factor.
      The letters E, S, A, B, and V denote solute dependent input parameters that come
      from scales related to a solute's polarizability, dipolarity (with some
      contribution from polarizability), hydrogen bond donating ability, hydrogen bond
      accepting ability, and molecular size, respectively. The e-, s-, a-, b-, and v
      coefficients and the constant, c, are determined via multiparameter linear least
      squares regression analysis of a data set comprised of solutes with known E, S,
      A, B, and V values and which span a reasonably wide range in interaction
      abilities. Thus, LSERs are designed to probe the type and relative importance of
      the interactions that govern solute retention. In this review, we include a
      synopsis of the various solvent and solute scales in common use in
      chromatography. More importantly, we emphasize the development and physico
      chemical basis of - and thus meaning of - the solute parameters. After
      establishing the meaning of the parameters, we discuss their use in LSERs as
      applied to understanding the intermolecular interactions governing various gas
      liquid and liquid-liquid phase equilibria. The gas-liquid partition process is
      modeled as the sum of an endoergic cavity formation/solvent reorganization
      process and exoergic solute-solvent attractive forces, whereas the partitioning
      of a solute between two solvents is thermodynamically equivalent to the
      difference in two gas/liquid solution processes. We end with a set of
      recommendations and advisories for conducting LSER studies, stressing the proper
      chemical and statistical application of the methodology. We intend that these
      recommendations serve as a guide for future studies involving the execution,
      statistical evaluation, and chemical interpretation of LSERs.

PMID- 16889783
TI  - Separation and determination of metallocyanide complexes of Fe(II), Ni(II) and
      Co(III) by ion-interaction chromatography with membrane suppressed conductivity
      detection applied to analysis of oil refinery streams (sour water).
AB  - A separation and determination method for the analysis of cyanometallic complexes
      of Fe(II), Ni(II) and Co(III) was developed to be applied to the analysis of
      petroleum refinery streams (sour water). Ion-interaction chromatography was used
      employing an analytical column IonPac NS1 10 microm and a chromatographic system
      ICS 2500 equipped with a membrane conductivity suppression ASRS ultra 4mm, both
      supplied by Dionex Corporation. The mobile phase was composed of 2 mmol l(-1)
      TBAOH, 1 mmol l(-1) Na(2)CO(3), 0.1 mol l(-1) NaCN and ACN (77:23, v/v), flowing
      at 0.7 ml min(-1). At the optimized conditions, detection limits estimated by the
      calibration curve parameters and relative standard deviation were: 0.002 mg CNl(
      1) and 3.1% for Fe(CN)(6)(4-); 0.003 mg CNl(-1) and 2.5% for Ni(CN)(4)(2-) and
      0.003 mg CNl(-1) and 2.8% for Co(CN)(6)(3-). Sour water samples without any
      pretreatment (except membrane filtration) from a petroleum refinery in Brazil
      were analyzed successfully by external calibration method.

PMID- 16889785
TI  - High performance liquid chromatography/electron spin resonance/mass spectrometry
      analyses of radicals formed in an anaerobic reaction of 9- (or 13-) hydroperoxide
      octadecadienoic acids with ferrous ions.
AB  - The oxidation of linoleic acid yields isomeric acyl hydroperoxides. In order to
      clarify the relation between the lipid peroxide-derived radicals and the toxicity
      of the lipid peroxide, identification of the lipid-derived radicals is essential.
      In this paper, high performance liquid chromatography/electron spin
      resonance/mass spectrometry (HPLC/EPR/MS) analysis of the radicals was performed
      for the reaction mixture containing 9-hydroperoxy-(10E,12E)-octadeca-10,12
      dienoic acid (9EE-OOH) [or 13-hydroperoxy-(9Z,11E)-octadeca-9,11-dienoic acid
      (13ZE-OOH)] under an aerobic condition or an anaerobic condition. Following
      radicals were identified from 9EE-OOH (or 13EZ-OOH) by using high performance
      liquid chromatography/electron spin resonance spectrometry (HPLC/EPR) and
      HPLC/EPR/MS: pentyl radical and isomers of epoxylinoleic acid radicals from 13EZ
      OOH under an anaerobic condition; 7-carboxyheptyl radical and pentyl radical from
      13EZ-OOH under an aerobic condition; 7-carboxyheptyl radical and pentyl radical
      from 9EE-OOH under an aerobic condition; 7-carboxyheptyl radical from 9EE-OOH
      under an anaerobic condition. These results showed that the formation of the
      respective radical species depends on oxygen concentration in the reaction
      mixtures to a great extent.

PMID- 16889786
TI  - Determination of ergosterol as an indicator of fungal biomass in various samples
      using non-discriminating flash pyrolysis.
AB  - Ergosterol is the major sterol constituent of most fungi. Since it is present in
      negligible amounts in higher plants, it can be used as a chemical marker for the
      presence of fungal contamination. A number of different ergosterol assays have
      been developed for the quantification of fungi in various samples. The paper
      presents the development of a new method for ergosterol detection based on the
      combination of non-discriminating flash pyrolysis with gas chromatography/mass
      spectrometry (Py-GC/MS). The design of the non-discriminating Py-GC/MS systems
      assures efficient transfer of high-molecular-weight pyrolysis products to the GC
      column for separation, followed by analyte detection by MS. The method was tested
      on different types of samples, including baker's yeast (Saccharomyces
      cerevisiae), moldy bread, indoor dust, and a leaf infected with powdery mildew.
      Ergosterol was detected in all these samples at levels ranging from approximately
      4 mg/g for the baker's yeast to approximately 6 microg/g for household dust. The
      main benefits of non-discriminating pyrolysis over other techniques include
      elimination of the need for sample preparation, small sample size required and
      short analysis time.

PMID- 16889787
TI  - Transport properties of some cationic polysaccharides 2. Charge density effect.
AB  - The charge density effect on the behavior of some cationic polysaccharides in
      aqueous and nonaqueous (methanol) solutions was studied by viscometric and
      conductometric measurements. The polyelectrolytes investigated contain quaternary
      ammonium salt groups, N-alkyl-N,N-dimethyl-2-hydroxypropylene ammonium chloride,
      attached to a dextran backbone. This new class of polyelectrolytes has various
      linear charge density parameters, xi, located below and above the critical
      threshold value of counterions condensation, xi(c)=1(xi=0.25-3.18). The
      viscometric data revealed that all copolymers exhibit a polyelectrolyte behavior
      and were plotted in the terms of Rao equation. The conductometric measurements of
      solutions of these copolymers were presented as a function of polymer
      concentration and charge density. The results were analyzed within the Manning's
      theory and lower experimental values of the equivalent conductivity than the
      theoretical ones were found. Possible reasons of this discrepancy have been
      discussed. The interaction parameters were evaluated and these were found to
      depend on both the polymer concentration and the charge density. The
      conductometric behavior of these cationic polysaccharides has shown that
      counterion condensation is not a threshold phenomenon, their association to the
      charged groups of the polyions taking place for xi>1 as well as xi<1.

PMID- 16889788
TI  - Chemico-electromechanical coupling in microporous media.
AB  - We determine the macroscopic transport properties of isotropic microporous media
      by volume-averaging the local Nernst-Planck and Navier-Stokes equations in
      nonisothermal conditions. In such media, the excess of charge that
      counterbalances the charge deficiency of the surface of the minerals is
      partitioned between the Gouy-Chapman layer and the Stern layer. The Stern layer
      of sorbed counterions is attached to the solid phase, while the Gouy-Chapman
      diffuse layer is assumed to have a thickness comparable to the size of the pores.
      Rather than using Poisson-Boltzmann distributions to describe the ionic
      concentrations in the pore space of the medium, we rely on Donnan distributions
      obtained by equating the chemical potentials of the water molecules and ions
      between a reservoir of ions and the pore space of the medium. The macroscopic
      Maxwell equations and the macroscopic linear constitutive transport equations are
      derived in the vicinity of equilibrium, assuming that the porous material is
      deformable. In the vicinity of thermodynamic equilibrium, the cross-coupling
      phenomena of the macroscopic constitutive equations of transport follow Onsager
      reciprocity. In addition, all the material properties entering the constitutive
      equations depend only on two textural properties, the permeability and the
      electrical formation factor.

PMID- 16889789
TI  - Solvothermal synthesis and characterization of anatase TiO2 nanocrystals with
      ultrahigh surface area.
AB  - Phase-pure, ultrafine nanocrystalline anatase with high specific surface area (up
      to 250 m(2) g(-1)) was obtained upon injection of a titanium alkoxide precursor
      into ethanol with designed volume of water under mild solvothermal conditions
      (<200 degrees C, 2 h). Primary particle sizes were tuned by adjusting various
      reaction parameters, with the smallest grain sizes occurring at low temperatures
      (140-150 degrees C), low initial alkoxide concentrations, and intermediate
      hydrolysis ratios (r identical with[H2O]/[Ti(OR)4]=5-10). Additionally,
      variations in the reaction temperature result in changes in particle morphology
      and distribution, with high-temperature samples exhibiting bimodal distributions
      of small spherical and larger cubic particles that suggest grain growth via
      Ostwald ripening. A crystalline product with high thermal stability and specific
      surface area up to 5 times that of commercial nano-titania can be obtained at a
      relatively low temperature of 150 degrees C. The physical properties of the
      titania samples obtained in this study suggest they might be well suited for
      catalytic applications.

PMID- 16889790
TI  - Jaw-phonatory coordination in chronic developmental stuttering.
AB  - A deficiency in sensorimotor integration in a person who stutters may be a factor
      in the pathophysiology of developmental stuttering. To test oral sensorimotor
      function in adults who stutter, we used a task that requires the coordination of
      a jaw-opening movement with phonation onset. The task was adapted from previous
      limb coordination studies, which show that movement coordination depends on
      intact proprioception. We hypothesized that adult stutterers would show deficient
      jaw-phonatory coordination relative to control participants. The task required
      initiation of phonation as a jaw-opening movement passed through a narrow spatial
      target. Target amplitude and jaw movement speed were varied. The stuttering group
      showed significantly higher movement error and spatial variability in jaw
      phonatory coordination compared to the control group, but group differences in
      movement velocity or duration were not found. The aberrant jaw-phonatory
      coordination of the stuttering participants suggests that stuttering is
      associated with an oral proprioceptive limitation, although, the findings are
      also consistent with a motor control deficit. LEARNING OUTCOMES: As a result of
      this activity, reader will (1) learn about a hypothesis and evidence supporting
      the view that a sensorimotor deficit contributes to chronic developmental
      stuttering and (2) will obtain information about the role of proprioception in
      multi-articulatory coordination and how it can be tested using an oral-phonatory
      coordination task.

PMID- 16889791
TI  - Anillin localization defect in cardiomyocyte binucleation.
AB  - Heart growth is augmented during early development by cardiomyocyte
      proliferation. In contrast, heart growth during postnatal life occurs by
      increasing cell size. Postnatal cardiomyocytes can undergo DNA synthesis, mitosis
      and binucleation. However, they lose the ability to complete cytokinesis. The
      underlying mechanism is poorly understood. It has been suggested that incomplete
      disassembly of contractile elements prohibits cytokinesis. Here, we show that
      serum-induced binucleation results in the normal disassembly of the contractile
      apparatus. In contrast, analysis of Aurora B and Anillin localization
      demonstrates that binucleation is characterized by asymmetric constriction, delay
      of furrow constriction and defective mid-body formation. Anillin fails to focus
      at the cortex in anaphase and shows an expanded localization around the mid-body
      during cytokinesis. p38 inhibition rescues the mid-body formation defect. We show
      that p38 accumulates during cytokinesis at the mid-body and suggest that p38
      activity has a regulatory role in cytokinesis. Microarray analysis reveals that
      p38 inhibition upregulates core components of the central spindle. Taken
      together, our results demonstrate that postnatal cardiomyocytes form a cleavage
      furrow and that binucleation is associated with an Anillin localization defect.

PMID- 16889792
TI  - Interaction between autoantibodies against the beta1-adrenoceptor and
      isoprenaline in enhancing L-type Ca2+ current in rat ventricular myocytes.
AB  - Autoantibodies against the beta1-adrenoceptor (beta1-AAB) in the serum of
      patients with dilated cardiomyopathy (DCM) are associated with stimulatory
      effects at cardiac beta1-adrenoceptors. They enhance cardiomyocyte shortening and
      increase the amplitude of L-type Ca2+ current, ICa. However, in contrast to the
      unselective beta-adrenoceptor agonist (-)-isoprenaline, beta1-AAB produce
      positive responses in a fraction of myocytes (responder cells) only and fail to
      do so in the remaining ones (non-responder cells). To understand this peculiar
      behaviour, the electrophysiological characteristics of ICa in response to beta1
      AAB and (-)-isoprenaline were investigated in responder and non-responder cells.
      The immunoglobulin G (IgG) fractions containing beta1-AAB (beta1-IgG) were
      obtained from patients with DCM undergoing immunoabsorption therapy. Only
      antibody preparations that tested positive in the neonatal rat cardiomyocyte bio
      assay by enhancing beating rate were used for further experimentation. Calcium
      currents were measured with the standard patch clamp technique in adult rat
      ventricular myocytes. Less than half of all cells exposed to beta1-IgG or
      purified beta1-AAB were responder cells in which ICa amplitude increased. ICa
      increase by beta1-IgG or (-)-isoprenaline was reversed by addition of carbachol.
      Exposure to subtype-selective beta-adrenoceptor blockers indicated that the
      effects of IgG were mediated via beta1-adrenoceptors. In responder cells, there
      were no differences between beta1-IgG- and (-)-isoprenaline-induced changes in
      current-voltage relationship of ICa, in the time constants of fast inactivation,
      and in steady-state activation and steady-state inactivation curves. (-)
      Isoprenaline (1 microM) effectively increased ICa after wash-out of antibody in
      all cells including non-responder cells. However, when non-responder cells were
      challenged with (-)-isoprenaline in the presence of beta1-IgG, any further
      increase in ICa was completely suppressed. Conversely, in responder cells, the
      cumulative concentration-response curves for (-)-isoprenaline on top of the
      autoantibodies reached the same maximum ICa amplitude as in control cells. From
      these interactions we conclude that beta1-AAB not only may enhance ICa via
      stimulation of beta1-adrenoceptors but also may inhibit beta1-adrenoceptor
      mediated increase upon stimulation with catecholamines suggesting a receptor
      interaction distinct from that with (-)-isoprenaline.

PMID- 16889793
TI  - Metrics that differentiate the origins of osmolyte effects on protein stability:
      a test of the surface tension proposal.
AB  - Osmolytes that are naturally selected to protect organisms against environmental
      stresses are known to confer stability to proteins via preferential exclusion
      from protein surfaces. Solvophobicity, surface tension, excluded volume, water
      structure changes and electrostatic repulsion are all examples of forces proposed
      to account for preferential exclusion and the ramifications exclusion has on
      protein properties. What has been lacking is a systematic way of determining
      which force(s) is(are) responsible for osmolyte effects. Here, we propose the use
      of two experimental metrics for assessing the abilities of various proposed
      forces to account for osmolyte-mediated effects on protein properties. Metric 1
      requires prediction of the experimentally determined ability of the osmolyte to
      bring about folding/unfolding resulting from the application of the force in
      question (i.e. prediction of the m-value of the protein in osmolyte). Metric 2
      requires prediction of the experimentally determined ability of the osmolyte to
      contract or expand the Stokes radius of the denatured state resulting from the
      application of the force. These metrics are applied to test separate claims that
      solvophobicity/solvophilicity and surface tension are driving forces for osmolyte
      induced effects on protein stability. The results show clearly that
      solvophobic/solvophilic forces readily account for protein stability and
      denatured state dimensional effects, while surface tension alone fails to do so.
      The agreement between experimental and predicted m-values involves both positive
      and negative m-values for three different proteins, and as many as six different
      osmolytes, illustrating that the tests are robust and discriminating. The ability
      of the two metrics to distinguish which forces account for the effects of
      osmolytes on protein properties and which do not, provides a powerful means of
      investigating the origins of osmolyte-protein effects.

PMID- 16889794
TI  - Evolutionary genomics of the HAD superfamily: understanding the structural
      adaptations and catalytic diversity in a superfamily of phosphoesterases and
      allied enzymes.
AB  - The HAD (haloacid dehalogenase) superfamily includes phosphoesterases, ATPases,
      phosphonatases, dehalogenases, and sugar phosphomutases acting on a remarkably
      diverse set of substrates. The availability of numerous crystal structures of
      representatives belonging to diverse branches of the HAD superfamily provides us
      with a unique opportunity to reconstruct their evolutionary history and uncover
      the principal determinants that led to their diversification of structure and
      function. To this end we present a comprehensive analysis of the HAD superfamily
      that identifies their unique structural features and provides a detailed
      classification of the entire superfamily. We show that at the highest level the
      HAD superfamily is unified with several other superfamilies, namely the DHH,
      receiver (CheY-like), von Willebrand A, TOPRIM, classical histone deacetylases
      and PIN/FLAP nuclease domains, all of which contain a specific form of the
      Rossmannoid fold. These Rossmannoid folds are distinguished from others by the
      presence of equivalently placed acidic catalytic residues, including one at the
      end of the first core beta-strand of the central sheet. The HAD domain is
      distinguished from these related Rossmannoid folds by two key structural
      signatures, a "squiggle" (a single helical turn) and a "flap" (a beta hairpin
      motif) located immediately downstream of the first beta-strand of their core
      Rossmanoid fold. The squiggle and the flap motifs are predicted to provide the
      necessary mobility to these enzymes for them to alternate between the "open" and
      "closed" conformations. In addition, most members of the HAD superfamily contains
      inserts, termed caps, occurring at either of two positions in the core
      Rossmannoid fold. We show that the cap modules have been independently inserted
      into these two stereotypic positions on multiple occasions in evolution and
      display extensive evolutionary diversification independent of the core catalytic
      domain. The first group of caps, the C1 caps, is directly inserted into the flap
      motif and regulates access of reactants to the active site. The second group, the
      C2 caps, forms a roof over the active site, and access to their internal cavities
      might be in part regulated by the movement of the flap. The diversification of
      the cap module was a major factor in the exploration of a vast substrate space in
      the course of the evolution of this superfamily. We show that the HAD superfamily
      contains 33 major families distributed across the three superkingdoms of life.
      Analysis of the phyletic patterns suggests that at least five distinct HAD
      proteins are traceable to the last universal common ancestor (LUCA) of all extant
      organisms. While these prototypes diverged prior to the emergence of the LUCA,
      the major diversification in terms of both substrate specificity and reaction
      types occurred after the radiation of the three superkingdoms of life, primarily
      in bacteria. Most major diversification events appear to correlate with the
      acquisition of new metabolic capabilities, especially related to the elaboration
      of carbohydrate metabolism in the bacteria. The newly identified relationships
      and functional predictions provided here are likely to aid the future exploration
      of the numerous poorly understood members of this large superfamily of enzymes.

PMID- 16889795
TI  - The equilibrium unfolding intermediate observed at pH 4 and its relationship with
      the kinetic folding intermediates in green fluorescent protein.
AB  - Folding mechanisms of a variant of green fluorescent protein (F99S/M153T/V163A)
      were investigated by a wide variety of spectroscopic techniques. Equilibrium
      measurements on acid-induced denaturation of the protein monitored by chromophore
      and tryptophan fluorescence and small-angle X-ray scattering revealed that this
      protein accumulates at least two equilibrium intermediates, a native-like
      intermediate and an unfolding intermediate, the latter of which exhibits the
      characteristics of the molten globule state under moderately denaturing
      conditions at pH 4. To elucidate the role of the equilibrium unfolding
      intermediate in folding, a series of kinetic refolding experiments with various
      combinations of initial and final pH values, including pH 7.5 (the native
      condition), pH 4.0 (the moderately denaturing condition where the unfolding
      intermediate is accumulated), and pH 2.0 (the acid-denaturing condition) were
      carried out by monitoring chromophore and tryptophan fluorescence. Kinetic on
      pathway intermediates were accumulated during the folding on the refolding
      reaction from pH 2.0 to 7.5. However, the signal change corresponding to the
      conversion from the acid-denatured to the kinetic intermediate states was
      significantly reduced on the refolding reaction from pH 4.0 to pH 7.5, whereas
      only the signal change corresponding to the above conversion was observed on the
      refolding reaction from pH 2.0 to pH 4.0. These results indicate that the
      equilibrium unfolding intermediate is composed of an ensemble of the folding
      intermediate species accumulated during the folding reaction, and thus support a
      hierarchical model of protein folding.

PMID- 16889796
TI  - The transmembrane domain of the oncogenic mutant ErbB-2 receptor: a structure
      obtained from site-specific infrared dichroism and molecular dynamics.
AB  - ErbB-2 is a member of the family of epidermal growth factor receptors, which
      shows an oncogenic mutation in the rat gene neu, Val664Glu in the transmembrane
      domain that causes permanent dimerisation and subsequently leads to
      uncontrollable cell division and tumour formation. We have obtained the alpha
      helical structure of the mutant transmembrane domain dimer experimentally with
      site-specific infrared dichroism (SSID) based on six transmembrane peptides with
      13C18O carbonyl group-labelled residues. The derived orientational data indicate
      a local helix tilt ranging from 28(+/-6) degrees to 22(+/-4) degrees. Altogether
      using orientational constraints from SSID and experimental alpha-helical
      constraints while performing a systematic conformational search including
      molecular dynamics simulation in a lipid bilayer, we have obtained a unique
      experimentally defined atomic structure. The resulting structure consists of a
      right handed alpha-helical bundle with the residues Ile659, Val663, Leu667,
      Ile671, Val674 and Leu679 in the dimerisation interface. The right-handed bundle
      is in contrast to the left-handed structures obtained in previous modelling
      efforts. In order to facilitate tight helical packing, the spacious Glu664
      residues do not interact directly but with water molecules that enter the
      bilayer.

PMID- 16889797
TI  - Causality of stem cell based neurogenesis and depression--to be or not to be, is
      that the question?
AB  - Mood disorders compose a considerable portion of the worldwide prevailing
      diseases with high suicide rates and urgent demand for novel therapeutic
      interventions as efficacious treatment is still lacking. Depression is thought to
      feature distinct morphological correlatives in the brain and has recently been
      linked to adult neurogenesis (NG) in the hippocampal formation. Numerous findings
      give rise to the hypothesis that depression and declining NG in the hippocampus
      may be causally connected. This implies that depressive symptoms could originate
      from impairments in NG and, vice versa, that improved NG could mediate
      antidepressant action and alleviate symptoms. Thus, great hopes rest on the
      question whether the observed increase in NG following antidepression treatment
      may have the potential to become a novel drug target and specific mechanism in
      the development of the next generation of antidepressants that specifically
      involves targeting of neuropoetic factors in addition to their "traditional"
      effects as modulators of synaptic transmission. Along the still hypothetical
      association of depression and NG, however, several controversies and unresolved
      questions exist with respect to the presently available data and interpretation.
      This article highlights and summarizes some of the most pressing issues and
      identifies the crucial ones that await urgent clarification and resolving.
      Without their reliable answering, the fascinating notion of a neurogenic basis
      for depression will remain to be greatly speculative.

PMID- 16889798
TI  - Changes in QEEG prefrontal cordance as a predictor of response to antidepressants
      in patients with treatment resistant depressive disorder: a pilot study.
AB  - INTRODUCTION: Previous studies of patients with unipolar depression have shown
      that early decreases of EEG cordance (a new quantitative EEG method) can predict
      clinical response. We examined whether early QEEG decrease represents a
      phenomenon associated with response to treatment with different antidepressants
      in patients with treatment resistant depression. METHOD: The subjects were 17
      inpatients with treatment resistant depression. EEG data and response to
      treatment were monitored at baseline and after 1 and 4 weeks on an antidepressant
      treatment. QEEG cordance was computed at three frontal electrodes in theta
      frequency band. The prefrontal cordance combines complementary information from
      absolute and relative power of EEG spectra. Recent studies have shown that
      cordance correlates with cortical perfusion. Depressive symptoms were assessed
      using Montgomery-Asberg Depression Rating Scale (MADRS). RESULTS: All 17 patients
      completed the 4-week study. All five responders showed decreases in prefrontal
      cordance after the first week of treatment. Only 2 of the 12 nonresponders showed
      early prefrontal cordance decrease. The decrease of prefrontal QEEG cordance
      after week 1 in responders as well as the increase in nonresponders were both
      statistically significant (p-value 0.03 and 0.01, respectively) and the changes
      of prefrontal cordance values were different between both groups (p-value 0.001).
      CONCLUSION: Our results suggest that decrease in prefrontal cordance may indicate
      early changes of prefrontal activity in responders to antidepressants. QEEG
      cordance may become a useful tool in the prediction of response to
      antidepressants.

PMID- 16889799
TI  - Increased risk of death in community-dwelling older people with white matter
      hyperintensities on MRI.
AB  - BACKGROUND: Previous studies in subjects with a history of stroke have shown that
      white matter hyperintensities (WMH) on MRI are associated with increased risk of
      death. However, it has not been determined whether WMH are independently related
      to death in community-dwelling older people without stroke. METHODS: In a sample
      of community-dwelling people over 75 years with no history of stroke or other
      neurological diseases, WMH on brain MRI T2-weighted sequences were classified as
      grade 0, grade 1, or grade 2. Grade 2 WMH were identified in 36 subjects. Age-
      and sex-matched grade 0 and grade 1 WMH groups were selected for comparison to
      the grade 2 WMH group. All subjects underwent an initial clinical evaluation and
      were followed for a median of 11.8 years (interquartile range=10.7 to 12.2
      years). Cox proportional-hazards analysis was used to determine the independent
      association between WMH and time to death from any cause. RESULTS: In an
      unadjusted analysis, grade 2 WMH was associated with death from any cause (hazard
      ratio=1.98; 95% confidence interval=1.06, 3.70). After adjustment for
      hypertension, high cholesterol, diabetes, and coronary artery disease, grade 2
      WMH remained significantly associated with death (hazard ratio=2.31; 95%
      confidence interval=1.21, 4.40) in these age- and sex-matched groups.
      CONCLUSIONS: Severe WMH increase the risk of death, even in community-dwelling
      elderly without stroke or other neurological disease, independent of other
      covariates including hypertension, age, and coronary artery disease.

PMID- 16889800
TI  - The quarter-power scaling model does not imply size-invariant hydraulic
      resistance in plants.

PMID- 16889801
TI  - PQN and DQN: algorithms for expression microarrays.
AB  - An ideal expression algorithm should be able to tell truly different expression
      levels with small false positive errors and be robust to assay changes. We
      propose two algorithms. PQN is the non-central trimmed mean of perfect match
      intensities with quantile normalization. DQN is the non-central trimmed mean of
      differences between perfect match and mismatch intensities with quantile
      normalization. The quantiles for normalization can be either empirical or
      theoretical. When array types and/or assay change in a study, the normalization
      to common quantiles at the probe set level is essential. We compared DQN, PQN,
      RMA, GCRMA, DCHIP, PLIER and MAS5 for the Affymetrix Latin square data and our
      data of two sets of experiments using the same bone marrow but different types of
      microarrays and different assay. We found the computation for AUC of ROC at
      affycomp.biostat.jhsph.edu can be improved.

PMID- 16889803
TI  - Adiponectin is regulated differently by chronic exercise than by weight-matched
      food restriction in hyperphagic and obese OLETF rats.
AB  - This study was intended to investigate the effects of chronic exercise on blood
      adiponectin level. Male Otsuka Long Evans Tokushima Fatty (OLETF) rats (26 weeks
      old) were divided to undergo either regular 12-week wheel running exercise (EX)
      or to have food restriction (FR) that resulted in body weight reduction similar
      to that in EX. Both EX and FR induced similar reductions in body weight,
      abdominal fat volume and plasma leptin concentration compared with ad libitum
      control. At the end of the study, although plasma adiponectin level was increased
      in FR, the adiponectin level did not change in EX. Plasma testosterone level was
      higher in EX than in either of the other two groups. A significant inverse
      relationship existed between plasma levels of adiponectin and testosterone for
      all groups. Our results suggested that 12-week voluntary wheel running exercise
      induces different effects on plasma adiponectin level than does food restriction,
      despite similar reduction in body weight, fat tissue mass and plasma leptin
      concentration. We speculate that the elevated plasma testosterone concentration
      might offset any hyperadiponectinemic effect of body weight and fat volume
      reduction in exercising rats.

PMID- 16889804
TI  - Human sensitivity to PhIP: a novel marker for prostate cancer risk.
AB  - 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) has been implicated in the
      development of colon, prostate and mammary gland tumors in rats. In this study,
      we developed a modified in vitro mutagen sensitivity assay, with activated PhIP
      (N-OH-PhIP) as the challenge mutagen and chromosome aberrations as the endpoint,
      and applied it in a pilot prostate cancer case-control study of 81 cases and 84
      age and ethnicity-matched controls. Our results showed significantly higher
      baseline breaks among the cases, mean+/-S.E.=1.86+/-0.23 versus 0.96+/-0.14 in
      controls; P=0.006. Individuals with high baseline breaks (dichotomized at the
      control median) had a 36% increased risk for PC (OR=1.36; 95% CI=1.08-1.72). In
      stratified analysis, high baseline breaks was associated in younger participants
      (< or = 60 years) with an OR of 1.71 (1.14-2.57) and in those with a positive
      family history of PC, an OR of 1.43 (0.97-2.11). PhIP treatment induced
      significantly higher breaks in cases, mean+/-S.E.=5.07+/-0.39 versus 3.83+/-0.24
      in controls; P=0.05. Higher PhIP-induced breaks was associated with an overall
      17% increased risk for PC (OR=1.17; 95% CI=1.03-1.33), a significantly increased
      risks (OR=1.19; 95% CI=1.00-1.41) among younger participants, non-smokers
      (OR=1.39, 1.03-1.88) and 1.20 (1.00-1.45) among those with no family history of
      PC. Results from this pilot study demonstrate differential sensitivity to PhIP
      among subgroups and therefore, this assay have potential as a susceptibility
      marker for prostate cancer risk.

PMID- 16889802
TI  - Exercise training improves insulin-induced and insulin-like growth factor-1
      induced vasorelaxation in rat aortas.
AB  - Improved vasorelaxant response is one of the beneficial effects of exercise
      training on vascular function. The mechanism for this response is, however,
      poorly understood. The aim of this study was to investigate the effects of
      exercise training on insulin-induced and insulin-like growth factor-1 (IGF-1)
      induced vasorelaxation. Fourteen 6-week-old male Wistar rats were randomly
      divided into sedentary control and exercise groups. For 12 weeks, the exercise
      group ran on a treadmill 60 min/day, 5 days/week. After exercise training,
      insulin-induced and IGF-1-induced vasorelaxant responses were evaluated by
      measuring the isometric tension of aortic rings. The vasorelaxant role of
      phosphatidylinositol 3-kinase (PI3K) and nitric oxide synthase (NOS) was examined
      by applying inhibitors, such as wortmannin (an inhibitor of PI3K) and N(omega)
      nitro-L-arginine methyl ester (L-NAME, a NOS inhibitor). In addition, we examined
      the vascular response to the NO donor, sodium nitroprusside (SNP). We found that:
      (1) exercise training significantly enhanced both insulin-induced and IGF-1
      induced vasorelaxation in rat aortas; (2) this vasorelaxant effect disappeared
      after the use of wortmannin or L-NAME; (3) there was no significant difference in
      SNP-induced vasorelaxation between control and exercise groups. Our findings
      indicate that exercise training enhances insulin-induced and IGF-1-induced
      vasorelaxant responses which are mediated through the PI3K-NOS-dependent pathway.

PMID- 16889805
TI  - Cortical correlates of TMS-induced phantom hand movements revealed with
      concurrent TMS-fMRI.
AB  - We studied an amputee patient who experiences a conscious sense of movement (SoM)
      in her phantom hand, without significant activity in remaining muscles, when
      transcranial magnetic stimulation (TMS) is applied at appropriate intensity over
      the corresponding sector of contralateral motor cortex. We used the novel
      methodological combination of TMS during fMRI to reveal the neural correlates of
      her phantom SoM. A critical contrast concerned trials at intermediate TMS
      intensities: low enough not to produce overt activity in remaining muscles; but
      high enough to produce a phantom SoM on approximately half such trials. Comparing
      trials with versus without a phantom SoM reported phenomenally, for the same
      intermediate TMS intensities, factored out any non-specific TMS effects on brain
      activity to reveal neural correlates of the phantom SoM itself. Areas activated
      included primary motor cortex, dorsal premotor cortex, anterior intraparietal
      sulcus, and caudal supplementary motor area, regions that are also involved in
      some hand movement illusions and motor imagery in normals. This adds support to
      proposals that a conscious sense of movement for the hand can be conveyed by
      activity within corresponding motor-related cortical structures.

PMID- 16889806
TI  - Chemistry and biological activity of secondary metabolites in Euphorbia from
      Iran.
AB  - The chemical constituents of some species of Euphorbia, which grow mostly in semi
      desert areas in Iran and on the Alborz Mountains in the north of Tehran, have
      been found to include chemotaxonomically important myrsinane diterpenoids and
      cycloartane triterpenoids. The Euphorbia plants collected in province of
      Azarbaijan in the northwestern part of Iran contained mostly derivatives of skin
      irritating ingenol esters. Some of the diterpenoids with myrsinane carbon
      skeleton inhibited enzymes such as alpha-glycosidase, urease, HIV-1 reverse
      transcriptase, and prolyl endopeptidase. They also showed analgesic and DNA
      damaging activities. The present review describes the chemistry and biological
      activity of several compounds isolated from different species of Iranian
      Euphorbia: diterpenoids with myrsinane skeletons, flavonoids, tannins, alkanes,
      sterols, mono-, sesqui- and triterpenoids, skin-irritating and tumor-promoting
      latexes and their active ingenol diterpenoids.

PMID- 16889807
TI  - Antiproliferative, cytotoxic and apoptogenic activity of Indian toad (Bufo
      melanostictus, Schneider) skin extract on U937 and K562 cells.
AB  - The antiproliferative, cytotoxic and apoptogenic activities of Bufo melanostictus
      (Indian common toad) skin extract (TSE) on U937 and K562 leukemic cell line has
      been investigated. TSE significantly (P<0.001) reduced the time-dependent cell
      proliferation and decreased MTT values in U937 and K562 cells. TSE (IC50 doses)
      suppressed the proliferating cell nuclear antigen expression in both the cells.
      It was demonstrated that, TSE (IC50 doses) primarily arrested the U937 and K562
      cells at G1 phase of the cell cycle. Confocal microscopy showed the altered
      fragmented nuclei and apoptotic bodies formation in TSE (IC50 doses) treated U937
      and K562 cells. Membrane blebbing, cell surface shrinkage and perforation were
      observed through scanning electron microscope. TSE-induced DNA fragmentation in
      U937 and K562 cells was reflected in single-cell gel electrophoresis. TSE
      significantly (P<0.001) increase the length-width ratio of DNA mass as compared
      to control in comet assay. The flow cytometric analysis of annexin-V binding to
      the cancer cells further supported the apoptotogenic activity of TSE. The effect
      of TSE on normal human peripheral blood mononuclear cells viability and
      cytotoxicity was studied in culture and found to be less cytotoxic than on the
      U937 and K562 cells. The findings from the present study suggested that TSE might
      possess potent antineoplastic agent having antiproliferative, cytotoxic and
      apoptogenic activity against U937 and K562 myeloid leukemic cells.

PMID- 16889808
TI  - Sexual dimorphism in venom of Bothrops jararaca(Serpentes: Viperidae).
AB  - Bothrops jararaca is an abundant snake in Brazil, and its venom has been studied
      exhaustively. The species exhibits adult size dimorphism in which female are
      larger. We registered the growth in Snout-Vent Length and weight of one litter
      (with 11 females and 12 males). We compared growth curves and venom profile
      between male and female of B. jararaca in order to establish the relationship of
      those characters and sex. Their venoms were analyzed when they were 36 months
      old, concerning SDS PAGE, protein content, proteolytic, hyaluronidasic,
      phospholipasic, blood-clotting, edematogenic, hemorrhagic, myotoxic activities,
      and lethality. Differences in the growth curves of the females and the males were
      significantly different after the 12th month of age, with the females growing
      faster. Females produced five times more venom than males. The electrophoretic
      patterns were variable: the venom from males had more protein bands than females.
      Venom composition varied significantly between males and females. Venom from
      females is more potent for hyaluronidasic, hemorrhagic, and lethality activities,
      whereas venom from males is more potent for coagulant, phospholipasic, and
      myotoxic activities. The variability of proteolytic and edematogenic activities
      were not significant. The important sexual dimorphism in body size and mass,
      amount of venom produced, and venom composition in B. jararaca may reflect a
      divergence in niche partitioning.

PMID- 16889809
TI  - Ultrasonic drying of foodstuff in a fluidized bed: Parametric study.
AB  - The application of high power ultrasound for dehydration of porous materials may
      be very effective in processes in which heat-sensitive materials such as
      foodstuffs have to be treated. In fact, high-intensity ultrasonic vibrations are
      capable of increasing heat and mass transfer processes in materials. The
      application of ultrasonic energy can be made alone or in combination with other
      kind of energy such as hot-air. In this case, ultrasound helps in reducing
      temperature or treatment time. The aim of this work is to study the effect of air
      flow rate, ultrasonic power and mass loading on hot-air drying assisted by a new
      power ultrasonic system. The drying chamber is an aluminium vibrating cylinder,
      which is able to create a high intensity ultrasonic field in the gas medium. To
      that purpose the chamber is driven at its centre by a power ultrasonic vibrator
      at 21.8 kHz. Drying kinetics of carrot cubes and lemon peel cylinders were
      carried out at 40 degrees C for different air velocities, with and without
      ultrasound. The results show that the effect of ultrasound on drying rate is
      affected by air flow rate, ultrasonic power and mass loading. In fact, at high
      air velocities the acoustic field inside the chamber is disturbed and the effect
      of ultrasound on drying kinetics diminishes.

PMID- 16889811
TI  - Broad target cell selectivity of Kaposi's sarcoma-associated herpesvirus
      glycoprotein-mediated cell fusion and virion entry.
AB  - The molecular mechanism of Kaposi's sarcoma-associated herpesvirus (KSHV, human
      herpesvirus 8) entry is poorly understood. We tested a broad variety of cell
      types of diverse species and tissue origin for their ability to function as
      targets in a quantitative reporter gene assay for KSHV-glycoprotein-mediated cell
      fusion. Several human, non-human primate, and rabbit cell lines were efficient
      targets, whereas rodent and all human lymphoblastoid cell lines were weak
      targets. Parallel findings were obtained with a virion entry assay using a
      recombinant KSHV encoding a reporter gene. No correlation was observed between
      target cell activity and surface expression of alpha3beta1 integrin, a proposed
      KSHV receptor. We hypothesize that target cell permissiveness in both the cell
      fusion and virion entry assays reflects the presence of a putative KSHV fusion
      entry receptor.

PMID- 16889810
TI  - Nitric oxide delivery by ultrasonic cracking: some limitations.
AB  - Nitric oxide (NO) has been implicated in smooth muscle relaxation. Its use has
      been widespread in cardiology. Due to the effective scavenging of NO by
      hemoglobin, however, the drug has to be applied locally or in large quantities,
      to have the effect desired. We propose the use of encapsulated microbubbles that
      act as a vehicle to carry the gas to a region of interest. By applying a burst of
      high-amplitude ultrasound, the shell encapsulating the gas can be cracked.
      Consequently, the gas is released upon which its dissolution and diffusion
      begins. This process is generally referred to as (ultra)sonic cracking. To test
      if the quantities of released gas are high enough to allow for NO-delivery in
      small vessels (o<200 microm), we analyzed high-speed optical recordings of
      insonified stiff-shelled microbubbles. These microbubbles were subjected to
      ultrasonic cracking using 0.5 or 1.7 MHz ultrasound with mechanical index MI>0.6.
      The mean quantity released from a single microbubble is 1.7 fmol. This is already
      more than the NO production of a 1mm long vessel with a 50 microm diameter during
      100 ms. However, we simulated that the dissolution time of typical released NO
      microbubbles is equal to the half-life time of NO in whole blood due to
      scavenging by hemoglobin (1.8 ms), but much smaller than the extravascular half
      life time of NO (>90 ms). We conclude that ultrasonic cracking can only be a
      successful means for nitric oxide delivery, if the gas is released in or near the
      red blood cell-free plasma next to the endothelium. A complicating factor in the
      in vivo situation is the variation in blood pressure. Although our simulations
      and acoustic measurements demonstrate that the dissolution speed of free gas
      increases with the hydrostatic pressure, the in vitro acoustic amplitudes suggest
      that the number of released microbubbles decreases at higher hydrostatic
      pressures. This indicates that ultrasonic cracking mostly occurs during the
      expansion phase.

PMID- 16889812
TI  - Characterisation of ocular fixation in humans by analysis of saccadic intrusions
      and fixation periods: a pragmatic approach.
AB  - Eye movements during fixation were recorded in 55 normal subjects with ages
      ranging from 21 to 81 years. We analysed ocular fixation recordings using
      measurements of saccadic intrusion amplitudes and frequencies along with fixation
      periods and mean fixation displacement. Viewing conditions included monocular,
      binocular and presence or absence of a visual fixation target. Visual feedback
      reduced the saccadic intrusion amplitudes but had no effect on fixation periods
      or mean fixation displacements. Binocular viewing had no effect on saccadic
      intrusion amplitudes, fixation periods or mean fixation displacements. A decrease
      in fixation periods and an increase in the number of saccadic intrusions with age
      was observed. This approach could be a clinically useful tool to quantify ocular
      fixation in neurological disease.

PMID- 16889813
TI  - Relationship between Dehalococcoides DNA in ground water and rates of reductive
      dechlorination at field scale.
AB  - Certain strains of Dehalococcoides bacteria can dechlorinate chlorinated
      ethylenes to harmless products. This study was conducted to determine if there is
      a valid association between the density of Dehalococcoides DNA in ground water
      and the observed rates of reductive dechlorination at field scale.
      Dehalococcoides DNA in water from monitoring wells was determined using the
      quantitative real time polymerase chain reaction (q-PCR) with DNA primer set
      specific for Dehalococcoides organisms. Dechlorination rate constants were
      extracted from field data using the BIOCHLOR software. Of the six conventional
      plumes surveyed, "generally useful" rates of dechlorination (greater than or
      equal to 0.3 per year) of cis-dichloroethylene (cis-DCE) and vinyl chloride (VC)
      along the flow path were observed at three sites where Dehalococcoides DNA was
      detected, and little attenuation of cis-DCE and VC occurred at two sites where
      Dehalococcoides DNA was not detected. At the two sites where there was no net
      direction of ground water flow, the relationship between the density of
      Dehalococcoides DNA in ground water and the trend in concentrations of
      chlorinated ethylenes over time in monitoring wells was not so consistent as that
      observed for the conventional plumes. A comparison of our study to a field study
      performed by Lendvay and his coworker indicated that monitoring wells did not
      efficiently sample the Dehalococcoides organisms in the aquifer.

PMID- 16889814
TI  - Algal-bacterial processes for the treatment of hazardous contaminants: a review.
AB  - Microalgae enhance the removal of nutrients, organic contaminants, heavy metals,
      and pathogens from domestic wastewater and furnish an interesting raw material
      for the production of high-value chemicals (algae metabolites) or biogas.
      Photosynthetic oxygen production also reduces the need for external aeration,
      which is especially advantageous for the treatment of hazardous pollutants that
      must be biodegraded aerobically but might volatilize during mechanical aeration.
      Recent studies have therefore shown that when proper methods for algal selection
      and cultivation are used, it is possible to use microalgae to produce the O(2)
      required by acclimatized bacteria to biodegrade hazardous pollutants such as
      polycyclic aromatic hydrocarbons, phenolics, and organic solvents. Well-mixed
      photobioreactors with algal biomass recirculation are recommended to protect the
      microalgae from effluent toxicity and optimize light utilization efficiency. The
      optimum biomass concentration to maintain in the system depends mainly on the
      light intensity and the reactor configuration: At low light intensity, the
      biomass concentration should be optimized to avoid mutual shading and dark
      respiration whereas at high light intensity, a high biomass concentration can be
      useful to protect microalgae from light inhibition and optimize the light/dark
      cycle frequency. Photobioreactors can be designed as open (stabilization ponds or
      high rate algal ponds) or enclosed (tubular, flat plate) systems. The latter are
      generally costly to construct and operate but more efficient than open systems.
      The best configuration to select will depend on factors such as process safety,
      land cost, and biomass use. Biomass harvest remains a limitation but recent
      progresses have been made in the selection of flocculating strains, the
      application of bioflocculants, or the use of immobilized biomass systems.

PMID- 16889815
TI  - Effects of indoor drinking water handling on trihalomethanes and haloacetic
      acids.
AB  - In this study, different tap water handling strategies were investigated to
      evaluate the effects on two principal chlorinated DBPs, trihalomethanes (THMs)
      and haloacetic acids (HAAs). Tap water samples collected in the Quebec City
      (Canada) distribution system on a spatio-temporal basis were subjected to diverse
      indoor handling scenarios: storing water in the refrigerator, boiling water
      followed by storage and, finally, filtering water with a point-of-use commercial
      pitcher also followed by storage. In the first two cases, the use of covered and
      uncovered pitchers was investigated separately, while in the last case, both the
      use of new and used filters was compared. In all cases, maximum storage time was
      48h. Results demonstrated that in some cases, water handling scenarios have
      considerable effect, and in other cases, little or no effect. Removal of THM
      concentrations by simple storage was high (on average 30%) and very high by
      boiling and filtering with subsequent storage in the refrigerator (on average,
      87% and 92%, respectively). In scenarios where water was stored in uncovered
      pitchers (with or without previous boiling and filtering), the THM decrease was
      higher for increased storage times. However, storage did not have any effect on
      HAAs, whereas boiling decreased levels of trichloroacetic acid (TCAA) (on average
      42%) and increased levels of dichloroacetic acid (DCAA) (on average 35%),
      resulting in unchanged average levels of total HAAs. The use of the filtration
      pitcher decreased HAA levels dramatically (on average 66%). Percentages of change
      in chlorinated DBPs in the different scenarios varied according to initial
      concentrations in tap water (baseline water), that is, according to the spatio
      temporal variations of these substances in the distribution system. On the basis
      of these results, the paper discusses implications regarding public health
      protection and exposure assessment for epidemiological studies.

PMID- 16889816
TI  - Synthesis, structure, and hydrolytic reaction of trans-dichlorobis(diethanolamine
      N)palladium(II) with N-acetylated L-histidylglycine dipeptide.
AB  - The reaction of PdCl2, or K2PdCl4, with diethanolamine (DEA), in the molar ratio
      1:2, affords the trans-[PdCl2(DEA)2] complex. X-ray structure analysis of this
      complex confirmed the formation of the trans-isomer. The complex crystallizes in
      the space group P42bc. The central Pd(II) ion is coordinated in an almost ideal
      square-planar fashion with a small deformation of the Cl-Pd-Cl angle (175.6(7)
      degrees) due to N-H...Cl hydrogen bonding. The N-H group participates in a
      bifurcated interaction with the two symmetry related Cl- anions. The hydroxyl
      groups of the diethanolamine ligand form very strong hydrogen bonds between the
      complex units, thus leading to infinite zigzag (O-H...O-H...O-H..) chains in the
      crystal packing. The complex units are further connected by weaker intermolecular
      hydrogen bonds of the N-H...Cl type in a way to form layers parallel to the
      crystallographic (001) plane. The reaction between the trans-[PdCl2(DEA)2] or
      trans-[Pd(H2O)2(DEA)2]2+ complex and MeCOHis-Gly dipeptide at 1.5 < pH < 2.0 and
      at 25 degrees C leads to the regioselective cleavage of the amide bond involving
      the carboxylic group of the histidine. The cleavage of the substrate was fast and
      went almost to completion within less than one hour.

PMID- 16889817
TI  - Artificial ribonucleases: from combinatorial libraries to efficient catalysts of
      RNA cleavage.
AB  - Combinatorial libraries of small organic compounds capable of cleaving RNA were
      synthesized. The compounds contain benzene ring substituted with two residues of
      bis quaternary salt of diazabicyclo[2.2.2]octane (DABCO) bearing hydrophobic
      fragments of different length and structure, attached to DABCO at the bridge
      position. These compounds, lacking traditional functionalities involved in
      transesterification reaction, exhibit pronounced RNA cleavage activity. To
      identify the most active artificial ribonucleases, sublibraries and truncated
      libraries, containing compounds lacking one of substituents were synthesized.
      Analysis of ribonuclease activity of truncated libraries resulted in
      identification of the most active compounds, which are characterized by the
      presence of at least one long oligomethylene substituent.

PMID- 16889818
TI  - Effects of aqueous, dietary and combined exposures of cadmium to Ceriodaphnia
      dubia.
AB  - While effects of water-borne metal exposures on freshwater animals have been well
      documented, the effect of dietary metal exposure is less understood but is
      gaining importance. However, little attention has been given to the importance of
      combining both exposure pathways. In this study, we compared effects of aqueous
      ('water only'), dietary ('food only') and combined ('water+food') exposures of
      cadmium to the freshwater cladocerans, Ceriodaphnia dubia. Major test endpoints
      included survival, feeding rate and reproduction. The C. dubia three-brood
      reproduction tests were conducted according to the United States Environmental
      Protection Agency (U.S. EPA) methods. Three exposure scenarios were used:
      aqueous, dietary, and combined aqueous and dietary exposures. Results showed that
      all three exposures affected survival, feeding rate and reproduction of C. dubia.
      Interestingly, combined exposure showed contribution effects of aqueous and
      dietary exposures. Lower cadmium concentrations were needed in combined exposure
      to produce effects as compared to higher concentrations in aqueous or dietary
      exposure alone. These results demonstrated the potential importance of dietary
      and combined exposures for consideration of cadmium regulation and risk
      assessment of metals.

PMID- 16889819
TI  - The effect of coal and diesel particulates on the weathering loss of Portland
      Limestone in an urban environment.
AB  - Due to reductions in domestic usage, legislation and changes in fuel use, coal
      derived particulates in the UK urban atmosphere have been significantly reduced.
      However, a large increase in road usage and an expansion in the use of diesel
      engines, has meant that the majority of particulates, now present in the urban
      atmosphere, originate from vehicle exhausts. Particulate matter, resulting from
      coal combustion, has been recorded as being present in black patinas observed on
      some historic stone buildings and monuments and has been associated with
      accelerated weathering of stone surfaces as a result of enhanced gypsum
      formation. In contrast, the effects of particulates resulting from vehicle
      exhaust on stone are much less understood. To investigate this, a comparative
      study was undertaken using the technique of microcatchments under ambient
      atmospheric conditions. This compared the elemental composition and volume of
      precipitation runoff from Portland Limestone coated with three different
      particulate treatments. Treatments consisted of coal and diesel particulates,
      both separately and in combination. Combining these treatments attempts to
      investigate any synergistic effects that may occur when coal derived particulates
      are overlain by layers formed by particulates from more contemporary sources. It
      was found that diesel-coated samples were much darker in appearance and showed a
      significant reduction (P<0.05) in the overall rate of weathering loss when
      compared to untreated samples. Microcatchment runoff volume was reduced from
      diesel-coated Portland Limestone compared to untreated stone. Enhanced surface
      temperatures may be increasing the rate of moisture loss from the pore network
      between rainfall events. Since, generally, the pores must be full before runoff
      can occur, the reduction may be due to the differential volume of empty pore
      space between diesel-coated and untreated Portland Limestone.

PMID- 16889820
TI  - Detection of disseminated tumor cells in patients with gynecological cancers.
AB  - OBJECTIVES: The presence of disseminated tumor cells (DTC) in breast cancer
      patients is associated with poor prognosis. However, there are limited data about
      the prevalence and prognostic impact of DTC in patients with gynecological
      tumors. The aim of this study was to evaluate the presence of DTC in the bone
      marrow (BM) of patients with gynecological cancers and to correlate their
      presence with established prognostic factors. METHODS: BM aspirates of 201
      patients with primary ovarian (n=69), cervical (n=54) and endometrial cancer
      (n=78), undergoing surgery at the Department of Gynecology and Obstetrics,
      University Hospital, Tuebingen, Germany between 1/2002 and 01/2006, were included
      into the study. Cytokeratin (CK)-positive cells were identified by
      immunocytochemistry using the pancytokeratin antibody A45B/B3. RESULTS: The bone
      marrow positivity rate was 36% in ovarian, 26% in cervical and 17% in endometrial
      cancer, respectively. Presence of DTC was significantly correlated with FIGO
      (International Federation of Gynecology and Obstetrics) tumor stage (p<0.05). The
      recurrence rate was 14% in patients with CK-positive cells compared to 8% in CK
      negative patients (p=0.2). There was no correlation between DTC and other
      established prognostic factors including nodal status or grading except for
      cervical cancer. Patients with positive lymph node status were more likely to be
      bone marrow positive compared to those with negative lymph node status (p<0.05).
      CONCLUSIONS: Disseminated tumor cells seem to be a general phenomenon in
      epithelial tumors even though their clinical impact remains to be evaluated. The
      hypothesis that bone marrow is the homing site of disseminated tumor cells is
      further supported by these data since gynecological tumors only rarely
      metastasize to the skeletal system.

PMID- 16889821
TI  - The benefit of adjuvant radiation therapy in single-node-positive squamous cell
      vulvar carcinoma.
AB  - OBJECTIVE: To determine if adjuvant radiotherapy improves the survival of women
      with invasive squamous cell carcinoma of the vulva involving one inguinal node.
      METHODS: Demographic, pathologic, and treatment information was obtained on
      patients with vulvar cancers from the Surveillance, Epidemiology, and End Results
      database between 1988 and 2001. Kaplan-Meier estimates and Cox-proportional
      hazards model were used for analyses. RESULTS: Of the 490 patients with stage
      III, node-positive vulvar cancers, 208 had a single positive inguinal node. The
      median age of this group was 71 years (range: 29-100). 82.2% of patients were
      White, 7.2% were Hispanic, 7.7% were Black, 1.4% were Asian, and 1.4% were
      Others. 91.8% of patients underwent a radical vulvectomy with a unilateral or
      bilateral inguinal lymphadenectomy. The median number of lymph nodes resected was
      13 (range: 1-34). 102 women underwent adjuvant radiotherapy, while 106 did not
      receive any radiation treatment. Women who received adjuvant radiotherapy had a 5
      year disease-specific survival of 77.0% compared to 61.2% in those without
      radiotherapy (p=0.02). After stratifying the study group based on the extent of
      lymphadenectomy, we found that radiation treatment improved the survival of those
      with <or=12 lymph nodes removed (76.6% versus 55.1%, p=0.035). In those with more
      than 12 nodes resected, radiotherapy increased the survival from 66.7% to 77.3%,
      though this difference was not statistically significant (p=0.23). In
      multivariate analysis, younger age (p=0.01) remained as a significant prognostic
      factor for improved survival; however, adjuvant radiotherapy had a borderline
      significance (p=0.06). CONCLUSION: Our data suggest that adjuvant radiotherapy
      may improve the disease-specific survival of patients with single-node-positive
      vulvar cancer who underwent a less extensive lymph node resection (<or=12 nodes
      removed).

PMID- 16889822
TI  - Phase I trial of concurrent chemoradiation with weekly nedaplatin in patients
      with squamous cell carcinoma of the uterine cervix.
AB  - OBJECTIVE: This phase I clinical trial for cervical carcinoma had three
      objectives: to evaluate the toxicity of a concurrent chemoradiation regimen
      featuring weekly nedaplatin; to determine the recommended dose of nedaplatin for
      a phase II concurrent chemoradiation trial; and to evaluate the formula for
      predicting area under the curve data for nedaplatin through pharmacokinetic
      studies. PATIENTS AND METHODS: Twelve patients with locally advanced squamous
      cell carcinoma of the uterine cervix were enrolled. Nedaplatin was administered
      once a week for 6 weeks. The starting dose of nedaplatin was 25 mg/m(2)/week,
      with increments of 5 mg/m(2)/week planned for each dose level. Three cases were
      enrolled at each of the dose levels. Radiation therapy was delivered with both
      external beam teletherapy and intracavitary brachytherapy with HDR-RALS.
      Volunteering patients underwent pharmacokinetics studies during the second
      course. RESULTS: Nedaplatin at a dose of 25, 30, and 35 mg/m(2) was safely
      administered for three cases at each dose level. At a dose of 40 mg/m(2),
      however, all three cases had Grade 3 neutropenia. Observed area under the curve
      value and predicted value was closely correlated, with differences between the
      two area under the curve values within 25%. All 12 cases achieved a clinical
      complete response, as evaluated with RECIST. CONCLUSIONS: Our recommended dose
      for a phase II trial of concurrent chemoradiation with weekly nedaplatin is 35
      mg/m(2). The formula can predict unbound concentration of nedaplatin based on
      area under the curve within 25% error.

PMID- 16889823
TI  - Radiation therapy with concomitant paclitaxel and cisplatin chemotherapy in
      cervical carcinoma limited to the pelvis: a phase I/II study of the Gynecologic
      Oncology Group.
AB  - OBJECTIVES: To determine the maximum tolerated dose (MTD) of weekly paclitaxel
      and cisplatin chemotherapy concurrent with whole pelvic irradiation in women with
      locally advanced cervical cancer. METHODS: Consenting patients with stage IB2,
      IIA, IIB, IIIB and IVA carcinoma of the cervix (all cell types) were eligible for
      this phase I/II trial. Chemotherapy agents were administered in escalating doses
      to cohorts of three patients at each dose level, pending evaluation of toxicities
      from the previous dose level. RESULTS: Thirty-five eligible women were enrolled
      on this study, of whom 13 comprised the phase I component. The MTD was determined
      to be cisplatin 40 mg/m2 and paclitaxel 40 mg/m2 administered weekly for six
      cycles with external beam radiation therapy. An additional 21 patients were
      enrolled in the phase II component at the previously determined MTD, yielding a
      total of 22 patients at the MTD, of whom 19 were evaluable. Among the evaluable
      patients treated at the MTD, two had grade 3 or 4 gastrointestinal (GI)
      toxicities (representing 5 of 113 cycles administered to this cohort) and seven
      experienced grade 3 or 4 neutrophil toxicity, none occurring prior to the fourth
      cycle. Thrombocytopenia was rare. Radiation therapy was successfully completed in
      52% of patients at 8 weeks and in 79% of patients at 9 weeks, with a median of 59
      days. CONCLUSIONS: Paclitaxel and cisplatin combination chemotherapy concurrent
      with whole pelvic irradiation can be safely administered at the described MTD.

PMID- 16889825
TI  - Kinetics of adsorption of Zn(II) ion on chitosan derivatives.
AB  - The adsorption of Zn(II) ions from aqueous solution by chitosan derivatives (KCTS
      and HKCTS) was studied in a batch adsorption system. The adsorption capacities
      and rates of Zn(II) ions onto chitosan derivatives were evaluated. The adsorption
      isothermal data could be well interpreted by the Langmuir and Freundlich models.
      The kinetic experimental data properly correlated with the second-order kinetic
      model, which indicates that the chemical adsorption is the rate-limiting step.
      The apparent adsorption activation energy were 25.47 kJ mol- and 5.473 kJ mol-,
      respectively, and the second-order adsorption constant for KCTS and HKCTS were
      0.00311 g (mg min)(-1) and 0.005 g (mg min)(-1), respectively.

PMID- 16889824
TI  - Effect of angiotensin II with follicle cells and insulin-like growth factor-I or
      insulin on bovine oocyte maturation and embryo development.
AB  - The objective was to evaluate the effects of angiotensin II (Ang II), insulin
      like growth factor-I (IGF-I) and insulin on the nuclear and cytoplasmic
      maturation of bovine oocytes in the presence of follicular cells. Cumulus-oocyte
      complexes (COCs) were cultured for 22h in the presence of follicular cells
      (control with cells) and Ang II, IGF-I or insulin (treatments), or in the absence
      of follicular cells (control without cells). Using these five groups, Experiment
      1 was conducted with and without the addition of gonadotrophins. Only oocytes in
      the Ang II group resumed meiosis at rates (88.2+/-1.8% and 90.7+/-4.3% for
      oocytes cultured in the absence or presence of LH/FSH, respectively) similar to
      those observed for oocytes cultured in the absence of follicular cells (89.7+/
      0.3% and 92.6+/-2.6%; P<0.01). In Experiment 2, the effect of Ang II alone and in
      combination with IGF-I or insulin on oocyte maturation for 7h (germinal vesicle
      breakdown), 12h (metaphase I) and 22h (metaphase II) was evaluated in a design
      similar to that of the first experiment. Ang II plus IGF-I or insulin induced the
      resumption of meiosis, irrespective of the presence of gonadotrophins (P<0.01).
      Experiment 3 used groups similar Experiment 2 to determine the rate of subsequent
      embryo development, using fetal calf serum (FCS) in the culture medium. The COCs
      were cultured in maturation medium for 1h (1+23h), 12h (12+12h) or 24h in the
      presence of follicular cells and the respective treatments and for the remaining
      period in the absence of follicular cells to complete 24h. In Experiment 4, BSA
      was used in lieu of serum in the maturation medium in a 12+12h maturation system.
      Oocytes matured using the 12+12h system with BSA or FCS in the presence of Ang
      II+IGF-I had higher rates of blastocyst formation than the other treatments
      (P<0.05). In conclusion, Ang II reversed the inhibitory effect of follicular
      cells on nuclear maturation of bovine oocytes, irrespective of the presence of
      gonadotrophins, IGF-I and insulin. However, oocyte cytoplasmatic maturation
      (i.e., subsequent embryo development), was higher when Ang II and IGF-I were
      present in the maturation medium containing follicular cells cultured for 12+12h.

PMID- 16889826
TI  - Transmission X-ray microscopy of spider dragline silk.
AB  - We have investigated the structure of spider silk fibers from two different
      Nephila species and three different Araneus species by transmission X-ray
      microscopy (TXM). Single fibers and double fibers have been imaged. All images
      are in agreement with a homogenous density on length scales between the fiber
      diameter and the resolution of the instrument, which is about 25 nm.

PMID- 16889827
TI  - Granulocyte-based immune response against decellularized or glutaraldehyde cross
      linked vascular tissue.
AB  - Supporting structures derived from biological tissue have been used in numerous
      tissue-engineering applications. This study focuses on the immune response of
      human leukocytes toward decellularized or glutaraldehyde (GA) cross-linked
      vascular tissue in vitro. Porcine and human pulmonary roots were sterilized with
      antibiotics, decellularized or cross-linked with GA. Proteins of the vascular
      tissue were extracted and the migratory response of human leukocytes toward
      protein extracts was examined using an in vitro migration chamber. Transmigrated
      leukocytes were counted and subsets (lymphocytes, monocytes, granulocytes)
      analyzed by flow cytometry. Decellularization significantly reduced the migration
      of monocytes compared to native porcine tissue. Although the proportion of
      transmigrating lymphocytes was much lower, decellularization again reduced the
      migratory response. Surprisingly, after decellularization granulocyte migration
      was still significantly higher than the negative control. Results comparable to
      those obtained with porcine material were found when human tissue was used for
      the experiments. Interestingly, migratory behavior toward extracts of GA-fixed
      porcine tissue was similar to that of decellularized specimens. We have shown
      that decellularization of vascular tissue reduces lymphocyte and monocyte
      recruitment comparable to cross-linking treatment. However, the migration of
      granulocytes, which are also known to be strongly involved in early inflammatory
      reactions, could be abolished neither by decellularization nor by fixation with
      GA.

PMID- 16889828
TI  - Retrograde regulation of store-operated calcium channels by the ryanodine
      receptor-associated protein triadin 95 in rat skeletal myotubes.
AB  - The 95kDa triadin (or T95), the main skeletal muscle triadin isoform, negatively
      regulates the mechanism of excitation-contraction coupling. T95 is a ryanodine
      receptor (RyR)-interacting protein but it also possesses a calsequestrin
      interacting domain. RyR and calsequestrin are involved in Ca2+ signalling and,
      for instance, influence the activity of store-dependent Ca2+ channels (SOC). This
      work was undertaken to determine whether T95 was able to modulate the entry of
      Ca2+ through SOC. The experiments were carried out on differentiated rat myotubes
      over-expressing T95 or DsRed (control cells) by means of an adenovirus infection.
      Intracellular Ca2+ signals were analyzed using the Ca2+ indicator Fluo-4. The
      sarco-endoplasmic reticulum Ca2+-ATPase inhibitor thapsigargin was used to
      deplete intracellular Ca2+ stores. When applied in the presence of a Ca2+-free
      medium, thapsigargin elicited transient but long-lasting Fluo-4 responses by
      elevating the cytoplasmic concentration of Ca2+ ([Ca2+]i). The over-expression of
      T95 reduced the thapsigargin-dependent [Ca2+]i increase, with respect to control
      myotubes. Addition of extracellular Ca2+after the depletion of this Ca2+ pool was
      accompanied by a [Ca2+]i increase that was sensitive to the SOC blockers 2-APB,
      SKF-96365 and La3+. The over-expression of T95 reduced this Ca2+ influx, without
      changing its pharmacological properties, showing that T95 over-expression did not
      alter the properties of the SOC. In conclusion, the RyR-interacting molecule T95,
      recently shown to inhibit the excitation-contraction coupling, has also the
      ability to interfere with the skeletal muscle Ca2+ signalling by depressing
      thapsigargin-dependent Ca2+ release and influx.

PMID- 16889829
TI  - A novel group contribution method in the development of a QSAR for predicting the
      toxicity (Vibrio fischeri EC50) of ionic liquids.
AB  - To achieve better management of processes and products, information on toxicity,
      safety, and risk assessment of chemicals is required. Ionic liquids are compounds
      of high interest for industry because of their attractive properties as solvents,
      but the water solubility of these compounds may lead to aquatic pollution and
      related risks. Experimental toxicity evaluation (Vibrio fischeri EC(50)) is a
      measurement of aquatic toxicity but there are theoretically over 1 million ionic
      liquids, which makes it necessary to estimate their properties by means of
      quantitative structure-activity relationships (QSARs). A database of Vibrio
      fischeri EC(50) was assembled to develop a novel group contribution method for
      estimating the EC(50) of ionic liquids. From the results the group contributions
      of anion, cation and alkyl substitutions has been calculated. The group
      contribution method allows an estimation of different combinations of groups in
      the toxicity (EC(50)) of ionic liquids.

PMID- 16889830
TI  - Complement regulates inhalation tolerance at the dendritic cell/T cell interface.
AB  - Pulmonary exposure to innocuous aeroallergens is a common event leading to
      inhalation tolerance. Distinct subsets of pulmonary dendritic cells (DC) and
      regulatory T cells (T(Reg)) play critical roles in mediating and maintaining such
      tolerance. In asthmatics, the same aeroallergens drive a maladaptive, Th2-biased
      immune response resulting in airway inflammation and airway hyper-reactivity. The
      mechanisms underlying the breakdown of inhalation tolerance, leading to the Th2
      driven inflammation in rising numbers of asthmatic patients from industrialized
      countries remain elusive. The recent resurgence of interest in the role of the
      innate immune mediators in regulating adaptive immune response has sparked
      studies aimed at identifying the role of complement in allergic asthma. In this
      context, an unexpected role for the anaphylatoxin C5a receptor in allergic
      sensitization has been found. In models of experimental allergic asthma, ablation
      of C5aR signaling during initial allergen exposure either induced or enhanced Th2
      sensitization. Mechanistically, C5aR signaling directly affected the function of
      distinct pulmonary DC subsets that induce or control allergen-induced adaptive
      immune responses. Signaling pathways downstream of C5 may also impact the
      function of T(Reg), as T(Reg) from C5 sufficient, but not from C5 deficient mice,
      suppress DC activation and subsequent development of Th2-driven inflammation. The
      emerging paradigm is that constitutive local generation of C5a and C5aR signaling
      in airway DCs controls inhalation tolerance directly as well as indirectly
      through sensitization of airway DCs for T(Reg)-mediated immunosuppression.

PMID- 16889831
TI  - Impact of severity and bilaterality of visual impairment on health-related
      quality of life.
AB  - OBJECTIVE: To assess the impact of unilateral and bilateral visual impairment
      (VI) and its severity on health-related quality of life (HRQOL) in Latinos 40
      years and older. DESIGN: A cross-sectional population-based study, the Los
      Angeles Latino Eye Study (LALES). PARTICIPANTS: Five thousand three hundred
      seventy-seven LALES participants. METHODS: Health-related quality of life was
      measured by the 25-item National Eye Institute Visual Function Questionnaire (NEI
      VFQ-25) and the Medical Outcomes Study 12-Item Short Form Health Survey (SF-12).
      Visual acuity (VA) was measured by a standardized protocol. Based on the
      presenting VA, VI was classified as unilateral or bilateral impairment and as
      either mild (20/40-20/63) or moderate/severe (20/80 or worse). MAIN OUTCOME
      MEASURES: National Eye Institute VFQ-25 and SF-12 composite and subscale scores.
      RESULTS: The NEI VFQ mean composite score decreased from no VI (86) to bilateral
      moderate/severe VI (66) (P<0.006). Relative to participants with no VI, those
      with unilateral or bilateral VI at any severity level had significantly lower NEI
      VFQ-25 scores for 10 of the 12 subscales (P<0.05). The largest mean score
      differences between participants with and without VI were observed for subscales
      related to driving difficulties (42.5 points), vision-related dependency (29.1
      points), distance vision (27.0 points), and vision-related mental health (24.5
      points). No differences in SF-12 scores were found between participants with and
      without VI (P>0.05). CONCLUSION: Relative to persons with no VI, persons with
      bilateral mild and unilateral or bilateral moderate/severe VI report greater
      difficulties in performing most vision-dependent daily activities and experience
      vision-related dependency and poorer vision-related mental health. Because most
      visual function subscale scores were significantly lower in persons with
      bilateral mild and/or unilateral/bilateral moderate/severe VI, health care
      providers should consider intervention in these persons. Our findings provide
      further insight into the relationship between severity level, bilaterality of VI,
      and self-reported visual function. These data can be used to refine the
      determination of visual disability in persons with VI.

PMID- 16889832
TI  - Does dilated wavefront aberration measurement provide better postoperative
      outcome after custom LASIK?
AB  - PURPOSE: To compare outcomes after custom LASIK based on non-pharmacologically
      dilated (natural mesopic pupil) and pharmacologically dilated wavefront
      aberration measurement. DESIGN: Case-control study. PARTICIPANTS AND CONTROLS:
      The study group included 81 myopic eyes from 81 patients (mean preoperative
      spherical equivalent [SE], -4.15+/-1.97 diopters [D]). The control group
      consisted of 87 myopic eyes from 87 patients (mean preoperative SE, -4.98+/-2.00
      D). METHODS: The 81-eye study cohort was treated based on nonpharmacological low
      mesopic dilated wavefront aberration measurement (Zywave aberrometer), and the
      postoperative outcome was compared with that of the control group of 87 eyes
      treated, based on pharmacologically dilated (2.5% neosynephrine) wavefront data,
      using the Zyoptix platform. The same nomogram was used for both groups, which
      adjusts sphere based on the amount of preoperative higher-order aberration. All
      eyes had a low mesopic pupil diameter of > or =6.3 mm without pharmaceutical
      intervention. MAIN OUTCOME MEASURE: Postoperative 3-month visual acuity (VA),
      contrast sensitivity, and refractive error. RESULTS: Of the non-pharmacologically
      dilated eyes (study) and pharmacologically dilated (control) eyes, 96.3% and
      96.6%, respectively, attained postoperative uncorrected VA of 20/20 or better.
      Although 96.6% of the eyes were within the target SE of +/-0.50 D in the control
      group, 100% of the 81 study eyes were within an SE of +/-0.50 D postoperatively.
      The range of postoperative SE (-0.75 to +1 D) was slightly reduced among the
      study eyes (+/-0.50 D). Differences were not statistically significant.
      CONCLUSIONS: When a low mesopic pupil dilates to > or =6.3 mm, pharmacological
      dilation with wavefront-guided ablation may provide no additional benefit with
      regard to spherical accuracy when compared with nonpharmacological wavefront
      guided ablation. The use of the Rochester nomogram, which accounts for aberration
      interaction, provided excellent results with or without pharmacological dilation.

PMID- 16889833
TI  - Comparison of the magnitude and time course of macular thinning induced by
      different interventions for diabetic macular edema: implications for sequence of
      application.
AB  - PURPOSE: To determine estimates of the magnitude and time course of macular
      thinning induced by three interventions for diabetic macular edema (DME). DESIGN:
      Retrospective observational case series. PARTICIPANTS: Two hundred eleven eyes of
      133 patients of a private retina practice, each diagnosed with DME in > or =1
      eye. METHODS: Review of clinical charts and optical coherence tomography
      measurements of eyes receiving focal laser photocoagulation, intravitreal
      triamcinolone injection (IVTA), or vitrectomy compared to untreated fellow eyes
      without DME. MAIN OUTCOME MEASURES: Central subfield mean thickness (CSMT; in
      micrometers), total macular volume (cubic millimeters), visual acuity, and rates
      of increased macular thickening at follow-up. RESULTS: At 6 months follow-up,
      predicted change in CSMT is 0 mum for untreated fellow eyes without DME, -28 mum
      for eyes receiving focal laser, -83 mum for eyes receiving triamcinolone, and -92
      mum for eyes receiving vitrectomy. The predicted change in Early Treatment
      Diabetic Retinopathy Study letters read at 6 months is 0 for untreated fellow
      eyes without DME, 0 for eyes receiving focal laser, +3 for eyes receiving IVTA,
      and -1 for eyes receiving vitrectomy. Increased thickening of the macula after
      interventions designed to thin it were 25.4% for focal laser, 3.8% for IVTA, and
      19.0% for vitrectomy. CONCLUSIONS: Interventions for DME differ in effect size,
      durability of effects, and potential for subsequent increases in macular
      thickness. A prospective study to elucidate a preferred sequence of interventions
      in DME may be worthwhile.

PMID- 16889834
TI  - Acute neurotoxic effects of mancozeb and maneb in mesencephalic neuronal cultures
      are associated with mitochondrial dysfunction.
AB  - Recent studies suggest that exposure to agrochemicals may contribute to the
      development of idiopathic Parkinson's disease. Maneb (MB), a widely used Mn
      containing ethylene-bis-dithiocarbamate (EBDC) fungicide, has been implicated in
      selective dopaminergic neurotoxicity. In this study, we examine the potential
      neurotoxicity of mancozeb (MZ), a widely used EBDC fungicide that is structurally
      similar to MB, but contains both Zn and Mn. Primary mesencephalic cells isolated
      from Sprague-Dawley embryonic day 15 rat embryos were exposed in vitro to either
      MZ or MB to compare their cytotoxic potential. Exposure to 10-120 microM MZ or MB
      for 24h resulted in a dose-dependent toxicity in both the dopamine (DA) and GABA
      mesencephalic populations as assessed by a functional assay for high affinity
      transporter activity. Consistent with this, cell viability as well as tyrosine
      hydroxylase-positive neurons decreased with increasing doses of MZ or MB. Toxic
      potencies for MZ and MB were similar and no difference in sensitivity between the
      DA and GABA populations was observed with the fungicides. Exposure to ethylene
      thiourea, the major metabolite of either MZ or MB, was not toxic, implicating the
      parent compound in toxicity. Both the organic and Mn metal components of the
      fungicides were found to contribute to toxicity. Non-toxic exposures to the
      fungicides decreased ATP levels in a dose-dependent manner suggesting impairment
      of energy metabolism. In whole mitochondrial preparations isolated from adult rat
      brains, MZ and MB inhibited NADH-linked state 3 respiration. Mild to moderate
      mitochondrial uncoupling was also observed in response to the fungicides. In
      conclusion, our findings indicate that acute exposure to high doses of MZ and MB
      produce equipotent toxic effects in both DA and GABA neurons that may be
      associated with perturbations in mitochondrial respiration.

PMID- 16889835
TI  - Hershey Medical Center Technical Workshop Report: optimizing the design and
      interpretation of epidemiologic studies for assessing neurodevelopmental effects
      from in utero chemical exposure.
AB  - Neurodevelopmental disabilities affect 3-8% of the 4 million babies born each
      year in the U.S. alone, with known etiology for less than 25% of those
      disabilities. Numerous investigations have sought to determine the role of
      environmental exposures in the etiology of a variety of human neurodevelopmental
      disorders (e.g., learning disabilities, attention deficit-hyperactivity disorder,
      intellectual disabilities) that are manifested in childhood, adolescence, and
      young adulthood. A comprehensive critical examination and discussion of the
      various methodologies commonly used in investigations is needed. The Hershey
      Medical Center Technical Workshop: Optimizing the design and interpretation of
      epidemiologic studies for assessing neurodevelopmental effects from in utero
      chemical exposure provided such a forum for examining these methodologies. The
      objective of the Workshop was to develop scientific consensus on the key
      principles and considerations for optimizing the design and interpretation of
      epidemiologic studies of in utero exposure to environmental chemicals and
      subsequent neurodevelopmental effects. (The Panel recognized that the nervous
      system develops post-natally and that critical periods of exposure can span
      several developmental life stages.) Discussions from the Workshop Panel generated
      17 summary points representing key tenets of work in this field. These points
      stressed the importance of: a well-defined, biologically plausible hypothesis as
      the foundation of in utero studies for assessing neurodevelopmental outcomes;
      understanding of the exposure to the environmental chemical(s) of interest,
      underlying mechanisms of toxicity, and anticipated outcomes; the use of a
      prospective, longitudinal cohort design that, when possible, runs for periods of
      2-5 years, and possibly even longer, in an effort to assess functions at key
      developmental epochs; measuring potentially confounding variables at regular,
      fixed time intervals; including measures of specific cognitive and social
      emotional domains along with non-cognitive competence in young children, as well
      as comprehensive measures of health; consistency of research design protocols
      across studies (i.e., tests, covariates, and analysis styles) in an effort to
      improve interstudy comparisons; emphasis on design features that minimize
      introduction of systematic error at all stages of investigation: participant
      selection, data collection and analysis, and interpretation of results; these
      would include (but not be limited to) reducing selection bias, using double-blind
      designs, and avoiding post hoc formulation of hypotheses; a priori data analysis
      strategies tied to hypotheses and the overall research design, particularly for
      methods used to characterize and address confounders in any neurodevelopmental
      study; actual quantitative measurements of exposure, even if indirect, rather
      than methods based on subject recall; careful examination of standard test
      batteries to ensure that the battery is tailored to the age group as well as what
      is known about the specific neurotoxic effects on the developing nervous system;
      establishment of a system for neurodevelopmental surveillance for tracking the
      outcomes from in utero exposure across early developmental time periods to
      determine whether central nervous system injuries may be lying silent until
      developmentally challenged; ongoing exploration of computerized measures that are
      culturally and linguistically sensitive, and span the age range from birth into
      the adolescent years; routine incorporation of narrative in manuscripts
      concerning the possibility of spurious (i.e., false positive and false negative)
      test results in all research reportage (this can be facilitated by detailed,
      transparent reporting of design, covariates, and analyses so that others can
      attempt to replicate the study); forthright, disciplined, and intellectually
      honest treatment of the extent to which results of any study are conclusive--that
      is, how generalizable the results of the study are in terms of the implications
      for the individual study participants, the community studied, and human health
      overall; confinement of reporting to the actual research questions, how they were
      tested, and what the study found, and avoiding, or at least keeping to a minimum,
      any opinions or speculation concerning public health implications; education of
      clinicians and policymakers to critically read scientific reports, and to
      interpret study findings and conclusions appropriately; and recognition by
      investigators of their ethical duty to report negative as well as positive
      findings, and the importance of neither minimizing nor exaggerating these
      findings.

PMID- 16889837
TI  - Allosteric agonists of 7TM receptors: expanding the pharmacological toolbox.
AB  - Approximately 1% of the genome of higher organisms encodes seven-transmembrane
      (7TM) G-protein-coupled receptors, which control an extensive range of
      physiological processes and represent drug targets for nearly half of all drugs
      that are prescribed currently. To date, most drugs that target 7TM receptors
      interact via the same domain as the endogenous agonist, called the orthosteric
      site. However, the advent of functional screening assays has greatly increased
      the number of allosteric ligands identified. Such ligands bind to topographically
      distinct sites on 7TM receptors. In addition to modulating the affinity of
      orthosteric ligands, allosteric ligands can also alter the efficacy of
      orthosteric ligands and activate 7TM receptors in their own right. In this
      article, we briefly review the current status of putative allosteric agonists of
      7TM receptors, and discuss the promises and challenges that this class of ligand
      might pose for pharmacologists and the drug-discovery industry.

PMID- 16889836
TI  - A rationale for lowering the blood lead action level from 10 to 2 microg/dL.
AB  - Fifteen years ago, in 1991, the U.S. Centers for Disease Control and Prevention
      (CDC) established 10 microg/dL as the lowest level of concern for children's
      blood lead levels. This value is extremely important because, historically,
      policy makers and public health officials generally have acted to remove sources
      of lead exposure only after the CDC's level of concern had been exceeded. A
      growing body of evidence, however, reveals that blood lead levels below 10
      microg/dL may impair neurobehavioral development. There is now sufficient and
      compelling scientific evidence for the CDC to lower the blood lead action level
      in children. This review argues that a level of 2 microg/dL is a useful and
      feasible replacement. Although it can be argued, in turn, that no threshold for
      the health effects of lead is demonstrable, analytically a blood level of 2
      microg/dL is readily and accurately measured and provides a benchmark for
      successful prevention. Lowering the level of concern would encourage and
      accelerate the investments needed to ensure that children are protected from lead
      exposure in their homes, schools, and play settings. Such a program would also
      offer economic advantages because of the coupling between lead, educational
      attainment, earnings and anti-social conduct. By lowering the blood action level,
      CDC will promote policies and initiatives designed to further reduce children's
      exposure to this potent developmental neurotoxicant.

PMID- 16889838
TI  - Antiviral effects of mifepristone on human immunodeficiency virus type-1 (HIV-1):
      targeting Vpr and its cellular partner, the glucocorticoid receptor (GR).
AB  - The HIV-1 viral protein R, Vpr, increases virus replication in T cells and is
      necessary for the optimal infection of primary monocytes/macrophages and other
      non-dividing cells. Vpr interacts with the cellular glucocorticoid receptor (GR)
      and transactivates the HIV-1 LTR through glucocorticoid response element (GRE),
      an event that can be blocked by the GR antagonist, mifepristone. Results
      demonstrated that Vpr-induced transactivation of the HIV-1 LTR was inhibited by
      mifepristone in a dose-dependent manner by >60% at a 10 microM concentration.
      Infectivity assays using X4 and R5 viruses demonstrated antiviral effects on a
      dose-dependent regimen of mifepristone. The effects of mifepristone were also
      tested in latently infected cells that could be activated with extracellular Vpr
      protein and results indicated specific inhibition of virus reactivation in the
      presence of this antagonist.

PMID- 16889839
TI  - Satiety assessment in neonatally handled rats.
AB  - We have previously demonstrated that neonatal handling increases sweet food
      ingestion. In the present study, we examined whether food intake, using different
      kinds of food, is altered in neonatally handled animals, with or without inducing
      satiety using a sucrose solution. Abdominal fat, glycemia and hormones linked to
      appetite including leptin, ghrelin and insulin were also measured. We tested
      palatable food consumption in the homecage to verify whether environmental cues
      could influence ingestion. Nests of Wistar rats were either (1) non-handled or
      (2) handled (10 min/day). Handling was performed on days 1-10 after birth. When
      adults, rats were habituated to sweet food (Froot Loops, Kellogg's) and to
      palatable fiber pellets (Fiber One), Nestle). Sweet food consumption was
      increased in the neonatally handled group, when tested in the homecage, and also
      in the satiety experiment. These rats displayed a satiety curve when compared to
      the control group, which ate less but constantly. Handled rats exposed to a
      sucrose solution decreased sweet food ingestion, which did not occur in the
      control group. When exposed to a food with complex carbohydrates, these
      differences disappeared. There were no differences in body weight, abdominal fat
      or in glycemia, as well as no differences in plasma levels of insulin or leptin.
      However, ghrelin was decreased in neonatally handled rats. Neonatally handled
      rats demonstrated an increased consumption of sweet food, satiety responses to
      sucrose, as well as decreased levels of plasma ghrelin. It is possible that
      signaling mechanisms related to satiety, both peripherally and/or centrally may
      contribute to these behavioral findings.

PMID- 16889840
TI  - Vasodilatory effects of cholecystokinin: new role for an old peptide?
AB  - Cholecystokinin (CCK) peptides are involved in the control of multiple functions
      both in the central nervous system (CNS) and in the gastrointestinal tract where
      they act as neurotransmitters and regulate digestive functions. This review deals
      with the role of CCK peptides as vasoactive mediators. Recent work from our group
      demonstrates that CCK peptides induce neurogenic vasodilatation both in cerebral
      and mesenteric vessels. Such an effect is mediated by nitric oxide and seems to
      be presynaptic. These findings suggest that endogenous CCK peptides could be
      relevant vasodilatory agents involved in regulating both cerebral and splanchnic
      blood flow. We hypothesize here how such an effect could be useful in the
      interpretation of, in a new conceptual frame, the eventual contribution of CCK to
      some physiological and physiopathological events, such as splanchnic postprandial
      hyperaemia, panic attack or migraine.

PMID- 16889841
TI  - Lack of angiotensin II conversion to angiotensin III increases water but not
      alcohol consumption in aminopeptidase A-deficient mice.
AB  - Elevated central concentrations of the vasopressor octapeptide angiotensin (Ang)
      II increase the water intake in mammals. Recently, we showed that central AngII
      is also crucial in alcohol-consuming behavior. Since the heptapeptide AngIII, an
      AngII metabolite, is discussed to mediate AngII-related effects, we investigated
      water and alcohol consumption in mice, genetically deficient in aminopeptidase A
      (APA), a peptidase responsible for AngII conversion to AngIII. Sixteen male APA
      deficient mice and their age matched wild-type controls were monitored on their
      water intake under basal conditions and total fluid and alcohol intake before and
      after social stress in a two-bottle free-choice paradigm. Alterations were
      connected to the regulation in activity of Ang-related peptidases (APA, ACE;
      ACE2) in brain regions involved in alcohol intake and peripheral organs. In
      comparison to their wild-type controls, APA-deficient mice drank significantly
      more water but not more alcohol at all investigated time points. A reduction in
      water intake, as observed in wild-type animals after social stress, did not occur
      in knockout mice. However, the reduction in alcohol consumption after social
      stress was significantly reduced in both strains. Alcohol consumption upregulated
      all three peptidases in the kidney, but not in lung. Notable, renal ACE2 activity
      was significantly higher in APA-deficient mice under basal condition. While the
      inhibition of AngII metabolism to AngIII does not influence the alcohol intake,
      water consumption in mice deficient for APA was significantly elevated. These
      differences induced by an altered AngII/AngIII ratio oppose the hypothesis that
      central AngII and AngIII act in a congruent pattern.

PMID- 16889842
TI  - What are the impacts of chronic subclinic inflammation in patients with rheumatic
      mitral stenosis?

PMID- 16889843
TI  - Pulmonary hypertension associated with autoimmune hemolytic anemia: a case
      report.
AB  - We reported a case of a 68-year-old male who had pulmonary hypertension
      associated with autoimmune hemolytic anemia.

PMID- 16889844
TI  - Current clinical features, diagnostic assessment and prognostic determinants of
      patients with variant angina.
AB  - BACKGROUND: Clinical characteristics and outcome of patients with variant angina
      were assessed in the 1970-1980s of the past Century. The recent progress in
      prevention, diagnosis and treatment of coronary artery disease may have
      significantly modified clinical characteristics and prognosis of these patients.
      METHODS: From January 1991 to December 2002, 202 patients (57.1+/-12 years; 166
      men) were diagnosed to have variant angina at our Institute. Detailed clinical
      findings and clinical events were prospectively collected for each patient.
      RESULTS: The median time from the first angina attack to diagnosis was 2 months
      (range 1-276), with diagnosis requiring >6 months in 31.7% of patients. Coronary
      angiography (n=183) showed normal coronary arteries in 42.1% of patients and
      significant coronary stenoses (>50%) in 44.3%, with multi-vessel disease in 8.7%.
      Diagnosis of variant angina was done during coronary angiography in 3% of cases
      during the first half of the study period, but in 42% of patients in the second
      half of the study period. Major cardiac events (MCE, i.e., death, resuscitation
      from cardiac arrest, myocardial infarction) occurred in 41 patients (20.3%), with
      43.9% of events occurring within 1 month of symptom onset. The only variable
      significantly associated with MCE was the detection during angina of ST segment
      elevation in both anterior and inferior ECG leads (odds ratio 3.24; 95%
      confidence interval 1.43-7.36; P=0.005). CONCLUSION: Our data suggest that
      variant angina is still a frequently overlooked diagnosis, and a timely diagnosis
      would be crucial to prevent early life-threatening events. Patients with diffuse
      ST segment elevation on ECG are those at the highest risk of MCE, independently
      of angiographic findings.

PMID- 16889845
TI  - Autoimmunity in idiopathic dilated cardiomyopathy: from patients to molecules and
      back to patients.

PMID- 16889846
TI  - Cardiac pacing in balloon aortic valvuloplasty.
AB  - OBJECTIVE: To evaluate the rapid ventricular pacing in balloon aortic
      valvuloplasty to achieve balloon stability. MATERIAL AND METHODS: From September
      2004 to July 2005, a prospective protocol was carried out: ten patients with
      aortic valve stenosis were treated with this method. Patient's age ranged from 3
      to 16 years with mean age of 10.2+/-4.3 years. In all cases a bipolar pacing
      catheter was placed in the right ventricle. Rapid ventricular pacing was
      initiated at the rate of 150 per minute and was gradually increased to achieve a
      50% drop in systemic pressure. The balloon was inflated only after the pacing
      rate was reached and the blood pressure dropped. Pacing was continued until the
      balloon was completely deflated. RESULTS: The systolic gradients across the
      aortic valve before balloon dilatation ranged from 40 to 110 mm Hg, mean 68.5+/
      20 mm Hg. The pacing rate required to drop the pressure by 50% ranged from 170 to
      250 per minute, mean 209+/-25. Balloon stability at time of inflation was
      achieved in all cases with no balloon movement. The post ballooning gradients
      ranged from 5 to 28 mm Hg, mean 19.7+/-8.3 mm Hg (p<0.001). In all cases there
      was no change in aortograms, performed before and after balloon dilatation in
      aorta, except in one patient who developed grade I aortic regurgitation.
      CONCLUSIONS: Rapid ventricular pacing appears to be an effective and a safe
      procedure to stabilize the balloon during balloon aortic valvuloplasty and is
      thought to decrease the incidence of aortic insufficiency.

PMID- 16889847
TI  - Assessment of vascular wall shear stress and implications for atherosclerotic
      disease.
AB  - Mechanical characteristics of circulation and vasculature, such as blood flow in
      combination with geometrical features, participate in the generation of several
      pathophysiological processes, such as development of blood vessel structure,
      chronic vessel tone regulation, atherosclerosis and others. We aim to briefly
      describe the basic mechanical and haemodynamic phenomena related to the forces
      applied to arterial walls, especially shear stresses and the shear-induced
      physiologic and pathophysiologic processes focusing on those related to
      atherosclerotic disease.

PMID- 16889849
TI  - Anomalous septal artery originating from the right coronary sinus and detection
      of the interarterial course using multislice computed tomography (MSCT).
AB  - Anomalies of the coronary arteries are uncommon but may produce life-threatening
      symptoms and myocardial ischemia. Multislice computed tomography (MSCT) has
      become a major technique for imaging the coronary arteries. We present a case of
      a patient with a septal and a circumflex arteries originating from the right
      coronary sinus and a duplicate left anterior descending artery. The interarterial
      course of the septal branch is clearly demonstrated with MSCT technique as the
      abnormal circumflex artery that coursed posterior to the aortic root.

PMID- 16889848
TI  - Transplantation of mesenchymal stem cells from human bone marrow improves damaged
      heart function in rats.
AB  - BACKGROUND: Bone marrow-derived mesenchymal stem cells (MSCs) are of great
      therapeutic potential after myocardial ischemic injury. However, little is known
      about the biological characteristics of MSCs in patients with coronary artery
      disease and their effects on infracted myocardium. The present study evaluated
      the biological characteristics of MSCs from patients with coronary artery disease
      and their effects after being transplanted into infarcted myocardium using a rat
      model. METHODS: Sternal bone marrow aspirates were taken at the time of coronary
      artery bypass graft surgery. Mononuclear cells isolated from bone marrow were
      cultured based on plastic adherence. The morphology and growth characteristics of
      MSCs were observed in primary and successive passages. A myocardial infarction
      model was created in 27 adult rats. Two weeks later, animals were randomized into
      two groups: culture medium (group I, n=13) or MSCs (2x10(6)) from early passages
      labeled with BrdU (group II, n=14) were injected into the infarcted myocardium.
      Echocardiography, histological examination, and reverse transcription-polymerase
      chain reaction (RT-PCR) were performed four weeks after cell transplantation.
      RESULTS: Flow cytometry analyses demonstrated that adherent spindle cells from
      bone marrow are mesenchymal stem cells (positive for CD29 and CD44, but negative
      for CD34 and CD45). Growth curves showed that MSCs have great proliferative
      capability especially at early passages. MSCs implantation in the infarcted
      border zone improved left ventricular function significantly in group II compared
      with group I. However, despite improved left ventricular function, we did not
      observe significant regeneration of cardiac myocytes. Immunohistochemistry
      revealed only the expression of desmin in the engrafted MSCs, a marker of
      premature myocyte. Moreover, the improved left ventricular function in this study
      seemed to be secondary to the beneficial reverse remodeling induced by the
      increase of collagen in infarcted zone, the decrease in the adjacent myocardium,
      and the increase of neovascularization (capillary density: 192+/-7.8/mm2 in group
      II vs. 165+/-5.9/mm2 in group I, P<0.05). Reverse transcription-polymerase chain
      reaction (RT-PCR) results showed the expression levels of collagen I, collagen
      III, SDF-1 (stromal cell-derived factor-1), and VEGF (vascular endothelia growth
      factor) in the infarcted border zone were significantly higher in the MSCs
      treated group. CONCLUSIONS: The MSCs from patients with coronary artery disease
      have a typical phenotype with highly proliferative potential and the engrafted
      MSCs may regulate extracellular collagens and cytokines to prevent the
      ventricular scar from pathologic thinning and attenuate the contractile
      dysfunction of the infarcted heart.

PMID- 16889850
TI  - Essential thrombocythemia presenting as unstable angina pectoris: what should the
      cardiologist know?

PMID- 16889851
TI  - Severe spontaneous three-vessel coronary artery spasm.
AB  - Coronary artery spasm is usually defined as a focal constriction of a coronary
      artery segment, reversible, and causing myocardial ischaemia by coronary blood
      flow restriction. Sometimes this condition is not focal and can compromise all
      the coronary tree. This is a very rarely described event. Generally, coronary
      vasospasm may occur spontaneously or induced, either physically by catheter,
      physiological manoeuvres (hyperventilation), or by pharmacological agents. It may
      also occur with or without underlying atheromatous coronary disease. The
      mechanism of coronary spasm remains unclear but endothelial dysfunction seems to
      be the main triggering factor in all causes.

PMID- 16889852
TI  - Recovery of global systolic function after primary angioplasty. Influence of
      coronary flow velocity reserve measured by transthoracic echocardiography.
AB  - BACKGROUND: Our objective were to know whether coronary flow velocity reserve
      measured by transthoracic Doppler echocardiography, as marker of microvascular
      integrity, affects the recovery of global systolic function. Secondly, we
      intended to define the best cut-off point of coronary flow velocity reserve to
      predict recovery of global systolic function. METHODS: We studied 57 patients
      with coronary flow recorded by transthoracic Doppler echocardiography, after
      suffering a first anterior acute myocardial infarction and undergoing a
      successful primary percutaneous coronary intervention (TIMI 3 flow). We measured,
      at discharge and at 1 month: ejection fraction, volume indexes and anterior wall
      motion score index. Coronary flow in left anterior descending artery was detected
      by transthoracic Doppler echocardiography and coronary flow velocity reserve was
      calculated. RESULTS: After applying ROC curves, 1.54 was the best cut-off value
      of coronary flow velocity reserve for detection of recovery of global systolic
      function. Ejection fraction only increased significantly in patients with normal
      coronary flow velocity reserve. Only end-systolic volume index increased
      significantly at 1 month in patients with impaired coronary flow velocity
      reserve. CONCLUSION: We showed that coronary flow velocity reserve, measured by
      transthoracic Doppler echocardiography, influence the recovery of global systolic
      function, mainly by ventricular dilation. Furthermore, a quite lower value of
      coronary flow velocity reserve than that used for diagnostic purpose should be
      used to predict improvement of systolic function.

PMID- 16889853
TI  - Congenital aortico-right atrial communication: a rare case in an adult patient.

PMID- 16889854
TI  - The effect of rapid lipid lowering with atorvastatin on autonomic parameters in
      patients with coronary artery disease.
AB  - Many cardiovascular disease states are associated with autonomic dysfunction,
      specifically sympathetic activation and parasympathetic withdrawal. Both these
      autonomic derangements are independently associated with adverse prognostic
      outcomes. HMG CoA reductase inhibitors (statins) reduce cardiovascular mortality
      and morbidity when compared to placebo in subjects with proven coronary artery
      disease (CAD), including sudden presumed arrhythmic death. As autonomic
      dysfunction is associated with arrhythmogenesis, statins may be having a
      beneficial effect on autonomic function in these subjects. We conducted a
      randomised, double-blind, placebo-controlled, cross-over study examining the
      effect of rapid short-term lipid lowering with a statin on autonomic function in
      CAD patients. Ten subjects with proven CAD (8 male, 2 female; mean age 63.4
      years) were randomised to receive either 80 mg atorvastatin or placebo over a 4
      week period followed by a 4 week washout, then the alternative treatment for a
      further 4 weeks. Autonomic parameters assessed were plasma noradrenaline levels
      on recumbency and 80 degrees head-up tilt, cold pressor testing, and heart rate
      variability (HRV) analysis. Plasma noradrenaline levels were significantly
      reduced (p=0.050) after 20 min rest in the recumbent position, with atorvastatin
      compared to placebo. A nonsignificant reduction in plasma noradrenaline with
      atorvastatin compared to placebo was observed in the prolonged 80 degrees head-up
      position (p=0.207). In addition, sympathovagal balance was shifted to greater
      vagal predominance with atorvastatin (low-frequency/high-frequency ratio in the
      HRV frequency domain) when compared to placebo, p=0.06. We found that rapid lipid
      lowering with atorvastatin reduces sympathetic nervous system in this pilot study
      of CAD patients. Larger trials are required to definitively address the effects
      of statins on autonomic activity in these patients.

PMID- 16889855
TI  - The effect of fluvastatin on cardiac outcomes in patients with moderate to severe
      renal insufficiency: a pooled analysis of double-blind, randomized trials.
AB  - BACKGROUND: Individuals with chronic kidney disease are at high risk for
      cardiovascular disease and have a high prevalence of hyperlipidemia. Lipid
      lowering therapy may help patients with renal disease reduce their risk for
      cardiovascular events. METHODS: A pooled analysis of 30 completed clinical trials
      compared the efficacy and safety profiles of fluvastatin in subgroups of patients
      with moderate to severe renal insufficiency (creatinine clearance < 50 ml/min)
      and patients with normal renal function or mild renal insufficiency (creatinine
      clearance > or = 50 ml/min). RESULTS: Changes in lipid parameters with
      fluvastatin treatment were similar for the compared patient subgroups.
      Fluvastatin treatment reduced combined cardiac death and myocardial infarction by
      41% compared with placebo among patients with moderate to severe renal
      insufficiency (hazard ratio, 0.59; p=0.007) and by 30% among patients with normal
      renal function or mild renal insufficiency (hazard ratio, 0.70; p=0.009). The
      relative reduction in the risk of major adverse cardiac events, a composite
      endpoint comprising cardiac death, nonfatal myocardial infarction, and coronary
      intervention procedures, with fluvastatin treatment was not significant for
      patients with moderate to severe renal insufficiency (hazard ratio, 0.83;
      p=0.18); in this patient subgroup, the incidence of coronary intervention
      procedures was similar between treatment groups. The safety profiles were similar
      for fluvastatin- and placebo-treated patients. CONCLUSIONS: The results of this
      pooled analysis indicate that fluvastatin is safe and effective for reducing
      cardiac death and nonfatal myocardial infarction in patients with moderate to
      severe renal insufficiency. Fluvastatin did not reduce the rate of coronary
      intervention procedures.

PMID- 16889856
TI  - The effect of granulocyte colony stimulating factor on regional and global
      myocardial function in the porcine infarct model.
AB  - BACKGROUND: Stem cell therapy has been shown to attenuate the reduction of left
      ventricular function following myocardial infarction. Most studies have utilized
      either a direct injection or intra-coronary infusion of cells, but cytokine
      mobilization of stem cells in the murine model of acute myocardial infarction has
      been reported to induce similar improvement in cardiac function. METHODS: An
      antero-apical infarction was induced in swine by balloon occlusion, followed by
      the daily administration of granulocyte colony stimulating factor (G-CSF) or
      placebo for 5 days. We used left ventricular angiograms and 2D echocardiograms to
      assess global function, and 3D echocardiograms to assess regional function prior
      to infarction, immediately following infarction, and at 8 weeks. Histologic
      evaluation was performed after sacrifice at 8 weeks. RESULTS: There was no
      significant difference in early or late post-infarction left ventricular ejection
      fraction or in myocardial histology between the two groups. Following G-CSF
      therapy, however, 3D echocardiography demonstrated that the regional ejection
      fractions of the infarcted segments showed a 50.3% improvement in the G-CSF pigs
      compared to a 7.4% deterioration in the untreated pigs (p=0.005). CONCLUSIONS:
      Global left ventricular ejection fraction remained unchanged, and there is no
      histologic evidence for infarct attenuation following G-CSF infusion in the
      porcine infarct-reperfusion model. There was recovery of regional function in the
      infarcted segment in the G-CSF pigs. These data suggest that bone marrow
      mobilization in larger species has limited potential as a therapy designed to
      replace infarcted myocardium or to improve overall cardiac function, although
      further studies are needed to examine regional effect in the infarct area.

PMID- 16889857
TI  - Repeated direct endomyocardial transplantation of allogeneic mesenchymal stem
      cells: safety of a high dose, "off-the-shelf", cellular cardiomyoplasty strategy.
AB  - BACKGROUND: Efficacy of cellular cardiomyoplasty seems to occur in a dose-related
      manner. However, the safety of multiple transendomyocardial transplantation
      procedures to administer high cell dosages has not been previously reported. The
      aims of this study were to assess the short- and intermediate-term results of a
      repeated cell administration strategy and evaluate the safety of an "off-the
      shelf" allogeneic mesenchymal stem cell (MSC) source. METHODS: Porcine bone
      marrow-derived MSCs were culture-expanded through three cycles in vitro before
      transplantation. Yorkshire swine weighing 30-40 kg were allocated to receive the
      total dose during 1 injection procedure or divided over 2 procedures separated by
      14 days, as follows: (i) 400x10(6) allogeneic MSC (n=5), (ii) 800x10(6)
      allogeneic MSC divided in 2 doses (n=5), (iii) cryopreservant vehicle containing
      10% DMSO, 5% porcine serum and 85% PlasmaLyte A, 14 days apart (n=2), or (iv)
      sterile saline 14 days apart (n=2). During each procedure, twenty 0.5 ml aliquots
      of the assigned injectant were administered using the Stiletto Endocardial Direct
      Injection Catheter System, targeting at the left ventricular anterior, septal and
      lateral walls under fluoroscopy. Vital signs and electrocardiograms were recorded
      during the procedure and at 24 h. The animals were examined daily and cardiac
      enzymes were measured immediately post-procedure, and on days 1, 15 and 90.
      Necropsy and histopathology were performed at day 90. RESULTS: Mean
      transendocardial injection procedure time was 40+/-10 min. All ventricular target
      areas were accessed by the Stiletto system. Ventricular ectopic beats and/or non
      sustained ventricular tachycardia associated with catheter contact or
      endomyocardial injections were observed in all cases. However, no sustained
      ventricular arrhythmia, anaphylaxis, or significant cardiac enzyme release was
      seen. One mortality resulted from air embolism during the procedure. All other
      swine survived from the time of recovery until planned sacrifice at day 90 and
      had normal physical examination findings. The 3-month histopathology showed no
      evidence of rejection, calcification, teratoma or myocardial infarction.
      CONCLUSION: Repeated endomyocardial transplantation of high dose, bone marrow
      derived allogeneic cells appeared safe in a large animal, human surrogate model.
      Such cellular cardiomyoplasty strategy warrants further investigation.

PMID- 16889858
TI  - Influence of storage temperature on microbial spoilage characteristics of haddock
      fillets (Melanogrammus aeglefinus) evaluated by multivariate quality prediction.
AB  - The proliferation of specific spoilage organisms (SSO) and quality changes were
      evaluated in haddock fillets stored in styrofoam boxes at 0, 7 and 15 degrees C
      and under temperature fluctuations. A rapid electronic nose technique was used to
      monitor different classes of compounds, representing microbial metabolites that
      were characteristic for the onset of spoilage odors. Photobacterium phosphoreum
      predominated among the spoilage bacteria and high levels of TVB-N were observed
      at sensory rejection. Pseudomonas spp. appeared to be responsible for the
      development of sweet, fruity spoilage odors in haddock fillets coinciding with
      increasing response of the electronic nose CO sensor. H(2)S-producing bacteria,
      most likely Shewanella putrefaciens, were associated with the H(2)S sensor's
      response at abusive temperature conditions. Partial Least Squares Regression
      (PLSR) was used as an explorative tool to provide a better understanding of the
      spoilage potential of SSOs, by evaluating models based on electronic nose
      responses and counts of specific spoilage organisms to predict sensory quality
      (Torry scores). The best prediction of the sensory quality was obtained by PLSR
      models based on five variables: the electronic nose sensors (CO, NH(3) and
      H(2)S), pseudomonads counts and a time-temperature variable. Good agreement
      between the predicted and experimental data indicates that these variables
      characterize the sensory quality of haddock fillets stored under different
      temperatures.

PMID- 16889859
TI  - Production of volatile compounds by Rhizopus oligosporus during soybean and
      barley tempeh fermentation.
AB  - Rhizopus oligosporus Saito can ferment soybeans or cereal grains to tempeh, a
      sliceable cake with improved nutritional properties. Volatiles produced by
      different R. oligosporus strains grown on malt extract agar (MEA), barley and
      soybean were investigated. The effect of co-cultivation with Lactobacillus
      plantarum on the production of volatiles was also studied. Volatile compounds
      were collected in situ by headspace diffusion and identified by GC-MS. The ten R.
      oligosporus strains that had different colony morphologies on MEA produced very
      similar volatile profiles, except for slight variations among the minor volatile
      compounds (e.g. sesquiterpenes). Likewise, practically no differences in volatile
      profiles were observed between three of the strains grown on soybeans. In
      contrast, the R. oligosporus volatile profile on soybean was different from that
      on barley from the same strain. Co-cultivation with L. plantarum did not
      influence volatile production by R. oligosporus. The dominant compounds produced
      on all three substrates were ethanol, acetone, ethyl acetate, 2-butanone, 2
      methyl-1-propanol, 3-methyl-1-butanol and 2-methyl-1-butanol. Acetaldehyde and 2
      methyl-propanal were also produced on MEA and barley, while 2-pentanone, methyl
      acetate, 2-butanol and 3-methyl-3-buten-1-ol were observed on soybeans. Ethanol,
      2-methyl-1-butanol and 3-methyl-1-butanol were the most abundant volatile
      compounds produced on MEA and barley, while 2-butanone was the dominant volatile
      metabolite on soybean. The mushroom odour compounds, 3-octanone and 1-octen-3-ol,
      were only detected from soybean and soybean tempeh.

PMID- 16889860
TI  - Long-term stability of marker gene expression in Prunus subhirtella: a model
      fruit tree species.
AB  - Transgenic trees currently are being produced by Agrobacterium-mediated
      transformation and biolistics. Since trees are particularly suited for long-term
      evaluations of the impact of the technology, Prunus subhirtella autumno rosa
      (PAR) was chosen as model fruit tree species and transformed with a reporter gene
      (uidA) under the control of the 35S promoter. Using Southern and GUS fluorometric
      techniques, we compared transgene copy numbers and observed stability of
      transgene expression levels in 34 different transgenic plants, grown under in
      vitro, greenhouse and screenhouse conditions, over a period of 9 years. An
      influence of grafting on gene expression was not observed. No silenced transgenic
      plant was detected. Overall, these results suggest that transgene expression in
      perennial species, such as fruit trees, remains stable in time and space, over
      extended periods and in different organs, confirming the value of PAR as model
      species to study season-dependent regulation in mature stone fruit tissues. While
      the Agrobacterium-derived Prunus transformants contained one to two copies of the
      transgenes, 91% of the transgenic events also contained various lengths of the
      bacterial plasmid backbone, indicating that the Agrobacterium-mediated
      transformation is not as precise as previously perceived. The implications for
      public acceptance and future applications are discussed.

PMID- 16889861
TI  - A hybridoma-based in vitro translation system that efficiently synthesizes
      glycoproteins.
AB  - Since a large number of eukaryotic proteins are glycoproteins, an efficient and
      easily available cell-free system for the production of recombinant glycoproteins
      is needed. We have successfully developed an efficient cell-free translation
      system derived from a monoclonal antibody-producing hybridoma for this purpose.
      While extracts from HeLa cells were very inefficient for production of an N
      glycosylated form of human immunodeficiency virus type-1 envelope protein 120
      (gp120), the hybridoma extract was able to fully N-glycosylate gp120. During cell
      free translation, eIF2alpha and eIF2alpha-kinases in the hybridoma extracts were
      observed to become phosphorylated due to the presence of essential supplements
      creatine phosphate and ATP. Addition of recombinant GADD34 and/or K3L to the
      extract efficiently lowered the phosphorylation of eIF2alpha, and thereby
      increased protein synthesis. By using this improved system, biologically active
      human choriogonadotropin (hCG), a glycoprotein hormone consisting of alpha and
      beta subunits was successfully synthesized. In conclusion, the hybridoma extract
      supplemented with GADD34/K3L should become a useful tool to produce recombinant
      glycoproteins.

PMID- 16889862
TI  - Binding of shrimp cellular proteins to Taura syndrome viral capsid proteins VP1,
      VP2 and VP3.
AB  - Viruses are a major cause of production losses in the world shrimp-farming
      industry. Despite this, little is known about viral-host interactions in shrimp
      due in part to the lack of continuous shrimp cell lines. Here, the yeast two
      hybrid assay system was employed to study interactions between three Taura
      syndrome viral capsid proteins (VP1-VP3) and proteins from a cDNA library of the
      black tiger shrimp Penaeus monodon. VP1 interacted with beta-actin, elongation
      factor 1alpha (EF1alpha), lysozyme (Lys) and laminin receptor/ribosomal protein
      p40 (Lamr/p40) containing a putative palindromic laminin binding region LMWWML.
      VP2 interacted with beta-actin and EF1alpha, while VP3 bound to the same proteins
      as VP1 except for Lamr/p40. In vitro pull-down assays confirmed these
      interactions. The most interesting interaction was specific binding between VP1
      and Lamr/p40 since Lamr/p40 has been identified as the mammalian cell receptor
      for several arthropod-borne viruses (arboviruses). A search of mosquito vector
      and Drosophila sequences at available databases revealed the presence of putative
      Lamr/p40 proteins with high homology to the Lamr/p40 from shrimp.

PMID- 16889863
TI  - The genomic termini of wild-type and vaccine strains of measles virus.
AB  - The genomic termini from 18 strains of measles virus (MV) including wild-type MVs
      from the pre-vaccine period, recent wild-type isolates and various vaccine
      strains were sequenced. The first 25 nucleotides of the 3' terminus and last 52
      nucleotides of the 5' terminus were conserved in all of the viruses examined.
      Nucleotides 26 and 42 of the 3' leader were A and G, respectively, in all
      genotype A viruses except Edmonston wild-type (Ed-WT). All non-genotype A viruses
      and Ed-WT had U in both positions. No consistent substitution pattern was found
      in the 5' trailer region of the genome. The nucleotide substitutions at positions
      26 and 42 in the 3' leader region were introduced into a MV-CAT mini-genome to
      test for their effect on the production of reporter protein in both a vaccinia T7
      driven, plasmid-based replication assay as well as in a helper virus system.
      Regardless of the source of the polymerase proteins or the natural leader
      sequence of the helper viruses, the mini-genome 26A42G produced more CAT protein
      than 26U42U. The nucleotide substitution at 26 had the greatest effect on CAT
      production. These results indicated that naturally occurring nucleotide
      variations in the 3' leader region can affect the levels of reporter protein
      synthesis, and presumably affected the level of replication of the virus.

PMID- 16889864
TI  - HIV-l and the microRNA-guided silencing pathway: an intricate and multifaceted
      encounter.
AB  - MicroRNAs (miRNAs) are approximately 21-24 nucleotide RNAs that mediate
      repression of messenger RNA (mRNA) translation through recognition of specific
      miRNA binding sites usually located in the 3' non-translated region. Designed to
      simulate miRNAs, small interfering RNAs represent a powerful genetic approach to
      potently inhibit gene expression by mediating cleavage of the intended mRNA
      target. This strategy has been applied successfully to suppress replication of
      several viruses, including human immunodeficiency virus type 1 (HIV-1). However,
      recent evidences indicate that viral RNAs may themselves be processed, to some
      extent, by the endogenous miRNA biosynthetic machinery in mammalian cells,
      extending previous observations in plants. The resulting viral miRNAs may exert
      regulatory effects towards host and/or viral genes that may influence viral
      replication and modulate the course of infection. Viral miRNA generation and/or
      action may be limited by counteraction through inhibitory viral RNAs and/or
      proteins. This review article will focus on the relationship between HIV-1 and
      miRNA-guided RNA silencing, and discuss the different aspects of their
      interaction. As we learn more about the mechanism and importance of small RNA
      based antiviral systems, a more intricate picture of the interaction between HIV
      1 and a proven antiviral defense mechanism in lower eukaryotes is emerging.

PMID- 16889865
TI  - Polymeric conjugates of mono- and bi-cyclic alphaVbeta3 binding peptides for
      tumor targeting.
AB  - The alphaVbeta3 integrin plays important roles in tumor-induced angiogenesis and
      tumor metastasis and hence, many small molecule alphaVbeta3 ligands have been
      developed for cancer diagnosis and therapy. Although these show good alphaVbeta3
      targeting, most have suboptimal pharmacokinetics and show rapid tumor washout. We
      studied the biodistribution and tumor targeting properties of N-(2
      hydroxypropyl)methacrylamide (HPMA) copolymer based conjugates of mono-(RGDfK)
      and doubly cyclized (RGD4C) alphaVbeta3 binding peptides. Endothelial cell
      adhesion studies showed similar affinity of HPMA-RGD4C and HPMA-RGDfK conjugate
      for alphaVbeta3 integrins. Scintigraphic images of tumor bearing mice
      demonstrated that both conjugates showed tumor localization at 24 h post
      injection and were retained at the tumor site until 192 h, whereas the efficient
      background clearance was observed over time. Necropsy organ counts showed that
      tumor accumulation of both HPMA-RGD4C and HPMA-RGDfK conjugates increased over
      time with peak accumulations at 4.9 +/- 0.9% and 5.0 +/- 1.2% ID/g, respectively.
      In contrast the background organ distribution rapidly cleared over time resulting
      in significant increases of tumor-to-background ratios. The radioactive dose as
      indicated by the area under curve (HPMA-RGD4C: 4825.3 microCi/g h and HPMA-RGDfK:
      4424.9 microCi/g h) was highest for the tumor. The polymer conjugates of RGD4C or
      RGDfK provide a means to enhance tumor uptake, decrease background accumulation,
      and enable selective delivery of therapeutic or diagnostic agents to tumor sites.

PMID- 16889866
TI  - Stable cationic microparticles for enhanced model antigen delivery to dendritic
      cells.
AB  - The objectives of this work were (i) to prepare physically stable cationic
      microparticles and (ii) to study the impact of the surface properties on
      microparticle phagocytosis and the phenotype of dendritic cells (DC). Protein
      loaded biodegradable microparticles from poly(lactic-co-glycolic acid) [PLGA]
      were produced in a micromixer-based w/o/w solvent evaporation procedure. Anionic
      particles were obtained by using polyvinyl alcohol (PVA) as stabilizing agent;
      for cationic surfaces cetyltrimethylammonium bromide (CTAB) and chitosan/PVA or
      DEAE-dextran/PVA blends were evaluated. In phagocytosis studies human monocytes
      and monocyte-derived DC were incubated with microparticles and analysed by flow
      cytometry. While CTAB modified microparticles lost their positive charge and
      aggregated due to CTAB desorption from the particle surface, the modification
      with chitosan and DEAE-dextran resulted in stable microparticles without cell
      toxicity. Due to a very low endotoxin content, phagocytosis of anionic and
      cationic microparticles did not induce an upregulation of maturation-associated
      surface markers on DC. DEAE-dextran modified microparticles showed an enhanced
      model protein delivery into phagocytic cells. Overall, PLGA microparticles are
      suitable vehicles for protein delivery to DC, which might be used for DC-based
      cell therapies.

PMID- 16889868
TI  - How well controlled are our type 2 diabetic patients in 2002? An observational
      study in North and Central Trinidad.
AB  - OBJECTIVES: To determine the proportion of diabetic patients that achieved
      glycemic control (HbA1c pound7.0%) and to explore some of the barriers to achieve
      this control. DESIGN: Cross-sectional, observational study. SETTING: Health
      centres in North and Central Trinidad. PATIENTS: One hundred and thirty-two type
      2 diabetics attending the health centres for more than 1 year. MAIN OUTCOME
      MEASURES: HbA1c levels and the proportion of patients who achieve glycemic
      control, HbA1c pound7.0%. RESULTS: The patients were categorized into two groups:
      well controlled, HbA1c Y7.0% and poorly controlled, HbA1c>7.0%. The majority of
      patients were poorly controlled (55.3%), duration of diabetes impacted negatively
      older patients and patients attending the clinics for longer periods were less
      likely to be well controlled. There was no correlation between pharmacological
      treatment, availability of individual counselling by a dietician or regular
      monitoring of blood glucose and glycemic control (p>0.05). CONCLUSION: A 44.7% of
      patients with type 2 diabetes were found to be well controlled. Old age (51-70
      years) and lengthy periods of attendance seem to be barriers to achieving
      glycemic control. This study highlights the fact that there is a need for re
      evaluation of the diabetic program since despite changes in the primary care
      system over the past 5 years a large proportion of diabetics are still
      uncontrolled.

PMID- 16889867
TI  - In vitro and in vivo intracellular liposomal delivery of antisense
      oligonucleotides and anticancer drug.
AB  - The specific aims of this investigation were (1) to show that conventional and
      PEGylated liposomes can penetrate cancer cells in vitro and in vivo; (2) to
      demonstrate that liposomes can be successfully used both for cytoplasmic and
      nuclear delivery of therapeutics, including anticancer drugs and antisense
      oligonucleotides; (3) to examine the specific activity of anticancer drugs and
      nucleotides delivered inside tumor cells by PEGylated liposomes; and (4) to
      confirm that simultaneous inhibition of pump and nonpump cellular resistance by
      liposomal ASO can substantially enhance the antitumor activity of traditional
      well established anticancer drugs in mice bearing xenografts of human multidrug
      resistant ovarian carcinoma. Experimental results show that PEGylated liposomes
      are capable of penetrating directly into tumor cells after systemic
      administration in vivo and do successfully provide cytoplasmic and nuclear
      delivery of encapsulated anticancer drug (doxorubicin, DOX) and antisense
      oligonucleotides (ASO). Encapsulation of DOX and ASO into liposomes substantially
      increased their specific activity. Simultaneous suppression of pump and nonpump
      resistance dramatically enhanced the ability of DOX for inducing apoptosis
      leading to higher in vitro cytotoxicity and in vivo antitumor activity.

PMID- 16889869
TI  - New perspectives on hereditary influences in metastatic progression.
AB  - Metastasis, the process by which cancer cells spread to distant sites and form
      secondary tumors, depends upon the ability of cells to escape the primary tumor,
      and colonize and proliferate in a novel microenvironment. Many mechanisms have
      been proposed to explain this phenomenon although no theory has comprehensively
      explained all biological observations. There is growing evidence that host
      hereditary factors modulate the ability of tumor cells to form metastatic
      lesions, and host genetic polymorphism could be a significant variable in this
      process. This review is intended to illustrate the role of hereditary variation
      in metastatic progression, how this integrates with currently proposed metastatic
      mechanisms, and the potential clinical impact on this frequently fatal
      consequence of cancer.

PMID- 16889870
TI  - Benefit of a combined treatment of cryotherapy and chemotherapy on tumour growth
      and late cryo-induced angiogenesis in a non-small-cell lung cancer model.
AB  - In the treatment of lung cancers, a local cryotherapy can be proposed as a
      palliative option for bronchial clearance. But this therapy can also be used as
      an adjuvant treatment, for instance in association with chemotherapy. We have
      already demonstrated differential biological effects of these therapies and the
      benefit to combine them. The aim of this study was to determine if this benefit
      observed at a molecular level was correlated with tumour growth. As vascular
      changes occur after cryotherapy, intratumoral angiogenesis was also studied.
      Cells from the A549 cell line were inoculated into SCID mice. Tumours were
      treated by cryotherapy (nitrous oxide cryoprobe), chemotherapy (injection of
      Vinorelbine) or both. Tumour growth was studied in each group and the T/C ratios
      were compared. Tumours treated by cryochemotherapy presented a significantly
      reduced volume and the lower T/C ratio, confirming the benefit of a combined
      treatment. Angiogenesis was assessed at variable time points after cryotherapy by
      immunohistochemical staining of VEGF and western blot analysis. A late cryo
      induced angiogenesis was observed 8-15 days after treatment (expression of VEGF
      increased from 13% in untreated tumours to 77 and 70%, respectively). To
      determine if this hypervascularization could enhance the efficiency of
      chemotherapy, the drug was injected 15 days after cryotherapy and the induction
      of cell death was investigated (morphological study, immunohistochemical staining
      of cleaved caspase-3, TUNEL). Necrosis was increased but not apoptosis,
      suggesting that though a crucial parameter, intratumoral microvessel density is
      not the only factor to consider to reach an optimal efficiency of a combined
      treatment.

PMID- 16889871
TI  - A robust approach for iterative contaminant source location and release history
      recovery.
AB  - Contamination source identification is a crucial step in environmental
      remediation. The exact contaminant source locations and release histories are
      often unknown due to lack of records and therefore must be identified through
      inversion. Coupled source location and release history identification is a
      complex nonlinear optimization problem. Existing strategies for contaminant
      source identification have important practical limitations. In many studies,
      analytical solutions for point sources are used; the problem is often formulated
      and solved via nonlinear optimization; and model uncertainty is seldom
      considered. In practice, model uncertainty can be significant because of the
      uncertainty in model structure and parameters, and the error in numerical
      solutions. An inaccurate model can lead to erroneous inversion of contaminant
      sources. In this work, a constrained robust least squares (CRLS) estimator is
      combined with a branch-and-bound global optimization solver for iteratively
      identifying source release histories and source locations. CRLS is used for
      source release history recovery and the global optimization solver is used for
      location search. CRLS is a robust estimator that was developed to incorporate
      directly a modeler's prior knowledge of model uncertainty and measurement error.
      The robustness of CRLS is essential for systems that are ill-conditioned. Because
      of this decoupling, the total solution time can be reduced significantly. Our
      numerical experiments show that the combination of CRLS with the global
      optimization solver achieved better performance than the combination of a non
      robust estimator, i.e., the nonnegative least squares (NNLS) method, with the
      same solver.

PMID- 16889872
TI  - Presence of immunoreactive salusin-alpha in human serum and urine.
AB  - Salusins, identified from a full-length enriched human cDNA library by
      bioinformatics analyses, show mitogenic, neuromodulatory and hemodynamic
      activities in rats. They are expressed in a wide variety of human tissues, but
      their precise structures and levels in human body fluids remain unknown. We
      developed a radioimmunoassay suitable for the detection of immunoreactive human
      salusin-alpha and characterized the molecular forms and concentrations of salusin
      alpha in human serum and urine. The assay allowed for measurement of
      immunoreactive salusin-alpha concentrations as low as 1 fmol/tube after
      extraction of serum with an octyl-silica column, and the concentration required
      for 50% inhibition of binding was 40 fmol/tube. Cross-reactivities with salusin
      beta and other bioactive peptides were negligible. Salusin-alpha-like
      immunoreactivity in normal human serum and urine ranged from 11.0 to 40.4 pmol/l
      (mean+/-S.D., 23.3+/-8.1 pmol/l, n=31) and from 18.6 to 367.3 pmol/l (mean+/
      S.D., 156.8+/-95.8 pmol/l), respectively. Reverse-phase high performance liquid
      chromatography coupled with radioimmunoassay detection revealed a major
      immunoreactive component that coeluted with authentic salusin-alpha. These data
      indicate the presence of salusin-alpha in human serum and urine, thereby
      verifying the initially predicted processing sites for salusin-alpha in humans.

PMID- 16889873
TI  - Molecular and cellular regulation of neurotensin receptor under acute and chronic
      agonist stimulation.
AB  - Neurotensin is a tridecapteptide acting mostly in the brain and gastrointestinal
      tract. NT binds two G protein coupled receptors (GPCR), NTS1 and NTS2, and a
      single transmembrane domain receptor, NTS3/gp95/sortilin receptor. NTS1 mediates
      the majority of NT action in neurons and the periphery. Like many other GPCRs,
      upon agonist stimulation, NTS1 is internalized, endocytosed, and the cells are
      desensitized. It is tacitly acknowledged that the intensity and the lasting of
      cellular responses to NT are dependent on free and functional NTS1 at the cell
      surface. Understanding how NTS1 expression is regulated at the membrane should
      provide a better comprehension towards its function. This review analyzes and
      discusses the current cellular and molecular mechanisms affecting the expression
      of NTS1 at the cellular membrane upon acute and chronic NT stimulation.

PMID- 16889874
TI  - New perfluoroalkylated amphiphilic methacrylates bearing sulfinyl group as
      monomers for biomedical applications: water content and oxygen permeability of
      their copolymers with DEGMA.
AB  - Perfluoroalkylated methacrylates 7a-c bearing sulfinyl group within a straight
      chain ester group, i.e. CH(2)=C(CH(3))CO(2)CH(2)CH(2)S(O)
      CH(2)CH(2)CF(2)(CF(2)CF(2))(n)CF(3) (n=1-3) were prepared by two alternative
      synthetic sequences from 2-[(polyfluoroalkyl)sulfanyl]ethanols
      HOCH(2)CH(2)SCH(2)CH(2)CF(2)(CF(2)CF(2))(n)CF(3) (n=1-3) in overall yields of 88
      91%. Copolymers of 7a-c with diethylene glycol methacrylate (DEGMA) prepared in
      bulk under radical conditions display high transparency, increased water content
      and good oxygen permeability properties, which are advantageous for their
      application in ophthalmology and as prosthetic materials.

PMID- 16889875
TI  - Synthesis and antimicrobial activity of pyranobenzoquinones related to the
      pyranonaphthoquinone antibiotics.
AB  - The synthesis and antimicrobial activity of isochromane-type analogs of the
      pyranonaphthoquinone antibiotics are reported. Isochromane derivatives with (17a,
      b) and without (22a, b) a C-4 hydroxyl moiety and their corresponding quinones
      (19a and 23), were prepared. Both quinones exhibited antimicrobial activity
      against Staphylococcus aureus, Bacillus atrophaeus and Streptococcus agalactiae,
      while the related isochromanes were inactive. The results suggest that the
      quinone moiety is important for biological activity while the C-4 hydroxyl may
      not be essential.

PMID- 16889877
TI  - Levels of rubella antibody among vaccinated and unvaccinated Portuguese mothers
      and their newborns.
AB  - Maternal and cord sera (231 pairs) were tested to measure rubella IgG levels,
      using a commercial immunoassay method with final fluorescent detection (ELFA).
      One hundred and twenty-two women had been vaccinated against rubella. Geometric
      mean concentrations (GMC) were not associated with time since vaccination. GMC of
      rubella IgG among vaccinated and unvaccinated mothers were respectively 66.6 and
      80.9IU/ml (p=0.29). The corresponding values for cord sera GMC were 140.6 and
      140.2IU/ml (p=0.99). These GMC values seem to have been influenced by increased
      transplacental transport efficiency (TTE) among vaccinated mothers. This was
      observed if TTE was measured as difference or ratio of cord-maternal
      concentration of rubella IgG, but was only statistically significantly (p=0.02)
      for ratio. TTE also seemed to be higher when antibody levels in mothers were
      below <15IU/ml. There seemed to be some interaction between susceptibility and
      vaccination status, but these results should be seen with caution. We do not know
      of a proven biological reason to support differential TTE in vaccinated and
      unvaccinated mothers. The sensitivity of the lab assay might have influenced the
      results, such that very low antibody levels in some vaccinated mothers were
      underestimates of true concentrations. Our finding that 38 mothers had antibody
      levels considered to be below the threshold for protection highlights the
      importance of implementing policies to vaccinate susceptible women of
      childbearing age.

PMID- 16889876
TI  - Interferon-gamma dose-dependently inhibits prostaglandin E2-mediated dendritic
      cell-migration towards secondary lymphoid organ chemokines.
AB  - Monocyte-derived human dendritic cells (MoDCs) are increasingly applied as
      cellular vaccines for cancer patients. Important features for their efficacy
      include high migratory responsiveness to lymph node-chemokines and most likely
      their ability to produce bioactive IL-12 p70 upon subsequent contact with CD40
      ligand-expressing T-cells. The current standard DC-maturation cocktail for
      clinical trials is inflammatory cytokines (TNF-alpha, IL-1beta and IL-6) combined
      with prostaglandin E(2) (PGE(2)), inducing phenotypically mature MoDCs with high
      migratory responsiveness to CCR7 ligands. This cocktail does not, however, induce
      or prime for production of IL-12 p70. Addition of IFN-gamma to PGE(2)-containing
      maturation cocktails has been shown to prime for substantial production of IL-12
      p70 by subsequent CD40 ligation, but the impact of IFN-gamma on phenotypic
      maturation and migratory responsiveness induced by PGE(2)-containing inflammatory
      stimuli still remains elusive. Here, we demonstrate that addition of IFN-gamma to
      the standard maturation cocktail decreased CCR7 mRNA and down-regulated CCR7
      expression on MoDCs in a dose-dependent manner. Moreover, addition of IFN-gamma
      was found to suppress MoDC-migration towards the CCR7-ligands CCL19 and CCL21.
      These novel findings indicate that addition of IFN-gamma to DC-maturation stimuli
      may have no beneficial impact on MoDC-vaccine efficiency and further implicate
      IFN-gamma as a negative feedback factor in DC migration towards draining lymph
      nodes when full-blown Th1-type responses are established. Such mechanism may
      restrict an uncontrolled and potentially harmful amplification of the adaptive
      Th1 response.

PMID- 16889878
TI  - Measuring, modelling and testing ozone exposure, flux and effects on vegetation
      in southern European conditions--what does not work? A review from Italy.
AB  - Ozone (O3) exposure at Italian background sites exceeds UN/ECE concentration
      based critical levels (CLe(c)), if expressed in terms of AOT40. Yet the
      occurrence of adverse effects of O3 on forests and crops is controversial.
      Possible reasons include (i) ability of response indicators to provide an
      unbiased estimate of O3 effects, (ii) setting of current CLe(c) in terms of cut
      off value and accumulation level, (iii) response functions adopted to infer a
      critical level, (iv) environmental limitation to O3 uptake and (v) inherent
      characteristics of Mediterranean vegetation. In particular, the two latter points
      suggest that critical levels based on accumulated stomatal flux (CLe(f)) can be a
      better predictor of O3 risk than CLe(c). While this concept is largely
      acknowledged, a number of factors may limit its applicability for routine
      monitoring. This paper reviews levels, uptake and vegetation response to O3 in
      Italy over recent years to discuss value, uncertainty and feasibility of
      different approaches to risk assessment.

PMID- 16889879
TI  - Bayesian population analysis of a harmonized physiologically based
      pharmacokinetic model of trichloroethylene and its metabolites.
AB  - Bayesian population analysis of a harmonized physiologically based
      pharmacokinetic (PBPK) model for trichloroethylene (TCE) and its metabolites was
      performed. In the Bayesian framework, prior information about the PBPK model
      parameters is updated using experimental kinetic data to obtain posterior
      parameter estimates. Experimental kinetic data measured in mice, rats, and humans
      were available for this analysis, and the resulting posterior model predictions
      were in better agreement with the kinetic data than prior model predictions.
      Uncertainty in the prediction of the kinetics of TCE, trichloroacetic acid (TCA),
      and trichloroethanol (TCOH) was reduced, while the kinetics of other key
      metabolites dichloroacetic acid (DCA), chloral hydrate (CHL), and dichlorovinyl
      mercaptan (DCVSH) remain relatively uncertain due to sparse kinetic data for use
      in this analysis. To help focus future research to further reduce uncertainty in
      model predictions, a sensitivity analysis was conducted to help identify the
      parameters that have the greatest impact on various internal dose metric
      predictions. For application to a risk assessment for TCE, the model provides
      accurate estimates of TCE, TCA, and TCOH kinetics. This analysis provides an
      important step toward estimating uncertainty of dose-response relationships in
      noncancer and cancer risk assessment, improving the extrapolation of toxic TCE
      doses from experimental animals to humans.

PMID- 16889880
TI  - A comparison study of effects of Echinacea extract and levamisole on phenytoin
      induced cleft palate in mice.
AB  - There are many reports that the teratogenic effects of phenytoin, especially
      cleft palate can be decreased by stimulation of maternal immune system. Also,
      there is some evidence that Echinacea extract and levamisole are immunomodulator
      drugs. So, in this study, we compared the prophylactic effects of levamisole and
      Echinacea extract on teratogenic effects of phenytoin. This study was performed
      on 32 pregnant mice that were divided into four groups. The first group (control
      group) received normal saline intraperitoneally and the other groups (test
      groups) received phenytoin (65 mg/kg intraperitoneally) at 10th day of gestation.
      Levamisole and extract of Echinacea purpurea were administrated at dose of 10 and
      360 mg/kg intraperitoneally, respectively, in along with and 12h later after
      phenytoin injection, in two groups. Fetuses were carried out in 19th day of
      gestation and after determination of weight and length; they were stained by
      Alizarin red-Alcian blue method. Cleft palate incidence was 16, 5.3, and 3.2% in
      fetuses of mice that received only phenytoin, phenytoin with levamisole, and
      phenytoin with Echinacea extract, respectively. Mean weight and length of fetuses
      of animals that received levamisole and Echinacea extract were significantly
      greater than those received only phenytoin. It is concluded that Echinacea can
      stimulate immune system more than levamisole and has better prophylactic effect
      on incidence of phenytoin-induced cleft palate, but it is not significant.

PMID- 16889882
TI  - An open-label study of quetiapine in the treatment of fibromyalgia.
AB  - The aim of this exploratory study was to systematically assess the potential
      effectiveness and tolerability of quetiapine, an atypical antipsychotic, for the
      treatment of patients with fibromyalgia. This was a unicentre, open-label study
      conducted in thirty-five outpatients, 18 years or older, who met the ACR criteria
      for fibromyalgia and who had not satisfactorily responded to their previous
      fibromyalgia treatment. Quetiapine, flexibly dosed (25-100 mg/day), was added to
      their original treatment regimen for 12 weeks. The primary outcome measure was
      the mean change from baseline to endpoint in the Fibromyalgia Impact
      Questionnaire (FIQ) total score. Secondary efficacy measures included mean
      changes from baseline to endpoint in the scores of the Clinical Global Impression
      (CGI) of Severity scale, Pittsburgh Sleep Quality Index (PSQI), Beck Depression
      Inventory (BDI), State-Trait Anxiety Inventory (STAI), 12-Item Short Form Health
      Survey (SF-12), and individual items of the FIQ. Thirty (85.7%) patients (mean
      age 47+/-7.9, 93.3% females) had a postbaseline evaluation and constituted the
      intent-to-treat efficacy sample. Mean FIQ total score decreased significantly by
      10.2 points from a baseline of 63.2 to 53.0 at study endpoint (p<0.001). A
      statistically significant reduction was observed in FIQ stiffness and FIQ fatigue
      subscores but not in FIQ pain subscore. Large effect sizes were observed for the
      FIQ total (1.04), CGI-severity (1.00) and PSQI (1.07), while moderate effect
      sizes (i.e.> or =0.50) were encountered in the FIQ fatigue, FIQ stiffness and SF
      12 mental component summary. Quetiapine was safely administered and well
      tolerated. Despite the lack of effect on pain, the significant and relevant
      improvement in overall efficacy measures and quality of life suggests that
      quetiapine may be a valuable drug for treatment of patients with fibromyalgia
      that should be further tested in double-blind, placebo-controlled trials.

PMID- 16889881
TI  - "A lot of sacrifices:" work-family spillover and the food choice coping
      strategies of low-wage employed parents.
AB  - Integrating their work and family lives is an everyday challenge for employed
      parents. Competing demands for parents' time and energy may contribute to fewer
      meals prepared or eaten at home and poorer nutritional quality of meals. Thus,
      work-family spillover (feelings, attitudes, and behaviors carried over from one
      role to another) is a phenomenon with implications for nutrition and health. The
      aim of this theory-guided constructivist research was to understand how low-wage
      employed parents' experiences of work-family spillover affected their food choice
      coping strategies. Participants were 69 black, white and Latino mothers and
      fathers in a Northeastern US city. We explored participants' understandings of
      family and work roles, spillover, and food choice strategies using open-ended
      qualitative interviews. Data analysis was based on the constant comparative
      method. These parents described affective, evaluative, and behavioral instances
      of work-family spillover and role overload as normative parts of everyday life
      and dominant influences on their food choices. They used food choice coping
      strategies to: (1) manage feelings of stress and fatigue, (2) reduce the time and
      effort for meals, (3) redefine meanings and reduce expectations for food and
      eating, and (4) set priorities and trade off food and eating against other family
      needs. Only a few parents used adaptive strategies that changed work or family
      conditions to reduce the experience of conflict. Most coping strategies were
      aimed at managing feelings and redefining meanings, and were inadequate for
      reducing the everyday hardships from spillover and role overload. Some coping
      strategies exacerbated feelings of stress. These findings have implications for
      family nutrition, food expenditures, nutritional self-efficacy, social
      connections, food assistance policy, and work place strategies.

PMID- 16889883
TI  - Chromium-picolinate induced ocular changes: Protective role of ascorbic acid.
AB  - Chromium-picolinate (Cr-picolinate) is a popular nutritional supplement; however
      its safety has been questioned with regard to its ability to act as a clastogen.
      The aim of the present work was to evaluate the biochemical, histological and
      morphological changes in the cornea and lens following oral administration of Cr
      picolinate and the possible protective effect of Vitamin C. Ninety male Sprague
      Dawley rats were divided into five groups included the control group, the groups
      treated with Cr-picolinate (0.8 and 1.5 mg/100 g b.w.) alone or in combination
      with Vitamin C (0.5 mg/100 g b.w.) for 8 weeks. The results indicated that the
      high dose of Cr-picolinate induced a significant decrease in SOD, GSH, Na(+)-,
      K(+)-ATPase levels, and a significant increase in MDA level. Severe morphological
      and histological changes in the cornea and lens accompanied with a decrease in
      the total soluble protein of the lens homogenate and changes in the crystalline
      fractions in lens. Vitamin C supplementation succeeded to restore these changes
      to great extent. It could be concluded that consumption of Cr-picolinate for a
      long time induced several hazards to cornea and lens. Supplementation with extra
      amounts of Vitamin C may be useful to restrain the Cr-picolinate induced ocular
      changes.

PMID- 16889884
TI  - CadA, the Cd2+-ATPase from Listeria monocytogenes, can use Cd2+ as co-substrate.
AB  - CadA is a membrane protein of the P-type ATPase family which is the major
      determinant of the resistance to Cd2+ in Listeria monocytogenes. During its
      catalytic cycle, CadA undergoes auto-phosphorylation from ATP at Asp398, which
      allows Cd2+ translocation across the membrane. In the reverse mode, Asp398 is
      phosphorylated from Pi. From the data obtained so far, the CadA catalytic
      mechanism is similar to that proposed for the sarcoplasmic reticulum Ca2+-ATPase,
      the model of the P-type ATPase family. We show here that CadA is sensitive to two
      different ranges of Cd2+ concentration. The 0.1-10 microM range of added CdCl2
      corresponds to Cd2+ binding at the transport site of unphosphorylated CadA which
      induces the reaction of the enzyme with ATP and impairs its reaction with Pi. The
      0.1-1 mM range of added CdCl2 could correspond to Cd2+ binding to the transport
      site accessible from the extracellular medium. In addition, although it is widely
      accepted that the actual substrate of P-type ATPases is the MgATP complex, we
      show here that CadA can also perform its cycle in the absence of Mg2+, using
      CdATP in the place of MgATP at the catalytic site.

PMID- 16889885
TI  - The A-minor motifs in the decoding recognition process.
AB  - The formation of A-minor motifs, mediated by adenines binding into the
      shallow/minor groove of stacked and helical Watson-Crick base pairs, is
      described. The conformations of the bacterial ribosomal decoding A site in
      various crystal structures are reviewed. The adenines A1492 and A1493 of the A
      site are seen either tucked in within the internal loop or bulging out and poised
      for interaction. This dynamic equilibrium contributes to the decoding process of
      the codon:anticodon base pairings. Aminoglycoside antibiotics lock the
      conformation of the A site in a single state with bulged-out adenines and thereby
      disrupt regulation of the decoding process.

PMID- 16889886
TI  - Exploration of the conformational space of myosin recovery stroke via molecular
      dynamics.
AB  - Muscle contractions are driven by cyclic conformational changes of myosin, whose
      molecular mechanisms of operation are being elucidated by recent advances in
      crystallographic studies and single molecule experiments. To complement such
      structural studies and consider the energetics of the conformational changes of
      myosin head, umbrella sampling molecular dynamics (MD) simulations were performed
      with the all-atom model of the scallop myosin sub-fragment 1 (S1) with a bound
      ATP in solution in explicit water using the crystallographic near-rigor and
      transition state conformations as two references. The constraints on RMSD
      reaction coordinates used for the umbrella sampling were found to steer the
      conformational changes efficiently, and relatively close correlations have been
      observed between the set of characteristic structural changes including the lever
      arm rotation and the closing of the nucleotide binding pocket. The lever arm
      angle and key residue interaction distances in the nucleotide binding pocket and
      the relay helix show gradual changes along the recovery stroke reaction
      coordinate, consistent with previous crystallographic and computational minimum
      energy studies. Thermal fluctuations, however, appear to make the switch-2
      coordination of ATP more flexible than suggested by crystal structures. The local
      solvation environment of the fluorescence probe, Trp 507 (scallop numbering),
      also appears highly mobile in the presence of thermal fluctuations.

PMID- 16889887
TI  - Effects of metal ion and solute conformation change on hydration of small amino
      acid.
AB  - The effects of metal ion and solute conformation change on the structures,
      energetic and dynamics of water molecules in the first hydration shell of amino
      acid were studied, using three forms of alanine (Ala) and Li(+)/Ala as model
      molecules. The theoretical investigations were started with construction of the
      test-particle model (T-model) potentials for all molecules involved and followed
      by molecular dynamics (MD) simulations of [Ala](aq) and [Li(+)/Ala](aq) at 298 K.
      The MD results showed that the hydrogen bond (H-bond) networks of water at the
      functional groups of Ala are strengthened by the metal ion binding, whereas the
      rotation of the N-C(alpha) bond from the angle phi=0 degrees to 180 degrees
      brings about smaller effects which cannot be generalized. It was also shown that
      the dynamics of water molecule in the first hydration shell of amino acid could
      be estimated from the total-average potential energy landscapes and the water
      exchange diagrams. The MD results suggested inclusion of an additional dynamic
      step in the water exchange process, in which water molecule moves inside a
      channel within the first hydration shell of solute, before leaving the channel at
      some point. The theoretical results reported in the present work iterated the
      necessity to include explicit water molecules in the model calculations.

PMID- 16889888
TI  - Oleanolic acid inhibits the activity of the multidrug resistance protein ABCC1
      (MRP1) but not of the ABCB1 (P-glycoprotein): possible use in cancer
      chemotherapy.
AB  - The effects of oleanolic acid (OA) on ABCB1 and ABCC1 activities were studied in
      a cell line constitutively expressing both proteins. It was observed that OA did
      not alter ABCB1 activity, but inhibited the activity of ABCC1 protein. This
      inhibition was reversible and only occurred in the presence of OA. In addition,
      OA did not alter the expression of ABCC1 mRNA. These results suggest that OA
      could be a good choice in the treatment of MDR tumours, either as a chemotherapic
      itself in tumours bearing ABCB1, or as an adjuvant in the chemotherapy of ABCC1
      expressing tumours.

PMID- 16889890
TI  - Effect of pH on cadmium biosorption by coconut copra meal.
AB  - Biosorption of cadmium ion by coconut copra meal, an agricultural waste product
      was investigated as a function of initial solution pH and initial cadmium
      concentration. Pseudo-second-order kinetic analyses were performed to determine
      the rate constant of biosorption, the equilibrium capacity, and initial
      biosorption rate. Cadmium biosorption by copra meal was found to be dependent on
      the initial solution pH and initial cadmium concentration. Ion exchange occurred
      in the initial biosorption period. In addition, mathematical relationships were
      drawn to relate the change in the solution hydrogen ion concentration with
      equilibrium biosorption capacity, initial cadmium concentration, and equilibrium
      biosorption capacity.

PMID- 16889889
TI  - Study on use of MSWI fly ash in ceramic tile.
AB  - In this work, MSWI (municipal solid waste incineration) fly ash is used as a
      blending in production of ceramic tile by taking advantage of its high contents
      of SiO(2), Al(2)O(3) and CaO. Besides, macro-performance and microstructure of
      the product as well as its leaching toxicity in practical application were
      studied by means of XRD, IR and SEM analysis, and leaching toxicity and
      sequential chemical extraction analysis of the product. It is found that when 20%
      fly ash is added, the product registers a high compressive strength of
      18.6MPa/cm(2) and a low water absorption of 7.4% after being sintered at 960
      degrees C. It is found that the glazed tile shows excellent resistance against
      leaching, in accordance with HVEP stand, of heavy metals with Cd<0.0002ppm,
      Pb<0.0113ppm and Zn<0.0749ppm, and Hg below the low detection limit. These
      results show that heavy metals are cemented among the solid lattice in the
      product and can hardly be extracted. Leaching toxicity of heavy metals in the
      product, especially Hg, Pb, Zn and Cd, is substantially reduced to less than one
      tenth of that in fly ash. In addition, specifications of Hg, Pb, Zn and Cd are
      largely changed and only a small portion of these heavy metals exists in soluble
      phases. These results as a whole suggest that the use of MSWI fly ash in ceramic
      tile constitutes a potential means of adding value.

PMID- 16889891
TI  - Equilibria and dynamics of liquid-phase trinitrotoluene adsorption on granular
      activated carbon: effect of temperature and pH.
AB  - Environmental regulations for removal of trinitrotoluene (TNT) from wastewater
      have steadily become more stringent. This study focuses on the adsorption
      equilibrium, kinetics, and column dynamics of TNT on heterogeneous activated
      carbon. Adsorption equilibrium data obtained in terms of temperature (298.15,
      313.15 and 323.15K) and pH (3, 8 and 10) were correlated by the Langmuir
      equation. In addition, the adsorption energy distribution functions which
      describe heterogeneous characteristics of porous solid sorbents were calculated
      by using the generalized nonlinear regularization method. Adsorption breakthrough
      curves were studied in activated column under various operating conditions such
      as temperature, pH, concentration, flow rate, and column length. We found that
      the effect of pH on adsorption breakthrough curves was considerably higher than
      other operating conditions. An adsorption model was formulated by employing the
      surface diffusion model inside the activated carbon particles. The model equation
      that was solved numerically by an orthogonal collocation method successfully
      simulated the adsorption breakthrough curves.

PMID- 16889892
TI  - Comparative analysis of the methods for SADT determination.
AB  - The self-accelerating decomposition temperature (SADT) is an important parameter
      that characterizes thermal safety at transport of self-reactive substances. A
      great many articles were published focusing on various methodological aspects of
      SADT determination. Nevertheless there remain several serious problems that
      require further analysis and solution. Some of them are considered in the paper.
      Firstly four methods suggested by the United Nations "Recommendations on the
      Transport of Dangerous Goods" (TDG) are surveyed in order to reveal their
      features and limitations. The inconsistency between two definitions of SADT is
      discussed afterwards. One definition is the basis for the US SADT test and the
      heat accumulation storage test (Dewar test), another one is used when the
      Adiabatic storage test or the Isothermal storage test are applied. It is shown
      that this inconsistency may result in getting different and, in some cases,
      unsafe estimates of SADT. Then the applicability of the Dewar test for
      determination of SADT for solids is considered. It is shown that this test can be
      restrictedly applied for solids provided that the appropriate scale-up procedure
      is available. The advanced method based on the theory of regular cooling mode is
      proposed, which ensures more reliable results of the Dewar test application. The
      last part of the paper demonstrates how the kinetics-based simulation method
      helps in evaluation of SADT in those complex but practical cases (in particular,
      stack of packagings) when neither of the methods recommended by TDG can be used.

PMID- 16889893
TI  - Test method selection, validation against field data, and predictive modelling
      for impact evaluation of stabilised waste disposal.
AB  - In setting criteria for landfill classes in Annex II of the EU Landfill
      Directive, it proved to be impossible to derive criteria for stabilised
      monolithic waste due to the lack of information on release and release
      controlling factors in stabilised waste monofills. In this study, we present a
      scientific basis, which enables a realistic description of the environmental
      impact of stabilised waste landfills. The work in progress involves laboratory
      testing of different stabilisation recipes, pilot scale studies on site and
      evaluation of field leachate from a full-scale stabilisation landfill. We found
      that the pHs in run-off and in percolate water from the pilot experiment are both
      around neutral. The neutral pH in run-off is apparently caused by the rapid
      atmospheric carbonation of those alkaline constituents that are released. The
      soil, used as a liner protection layer, controls the release to the subsurface
      below the landfill. This soil layer buffers pH and binds metals. The modelling
      results show that the chemistry is understood rather well. Differences between
      predicted and actual leaching might then be attributed to discrepancies in the
      description of sorption processes, complexation to organic matter and/or kinetic
      effects in the leaching tests. We conclude that this approach resulted in a new
      scientific basis for environmental impact assessment of stabilised waste
      landfills. The integrated approach has already resulted in a number of very
      valuable observations, which can be used to develop a sustainable landfill for
      monolithic waste and to provide guidance for the management of waste to be
      stabilised (e.g. improved waste mix design).

PMID- 16889894
TI  - Toxicity evaluation for the broad area of the asbestos mine of northern Greece.
AB  - The existing data regarding the quality of the environment in the asbestos mine
      of northern Greece (MABE) region related to the presence of asbestos are
      insufficient to determine the current pollution problem. In the present work, a
      first approach to this problem has been taken through a toxicity risk assessment.
      The environmental quality of an open air asbestos mine was evaluated over a long
      period of time by measuring and monitoring the concentration of asbestos fibres
      in air, soil and water. Air measurements were made to determine the concentration
      of asbestos fibres in the atmospheric air of the mine, the depositions and the
      nearby villages. The asbestos fibre concentration was also specified inside the
      building facilities of MABE. Analyses of soil, dust and water samples were
      carried out showing the presence of enormous quantities of chrysotile asbestos.
      The concentration of asbestos fibres in the atmospheric air was compared to older
      measurements that were taken at the same sampling points during the operation of
      the mine. The results of this work, in conjunction with individual researches
      that have been carried out in the past and with the evaluation of international
      standards of scientific and experience-based findings, provide a reliable
      framework with which to estimate the threat of MABE to its surrounding
      environment, and help to determine a basic criterion for the remediation and
      rehabilitation of the region. In addition, mathematical models based on human and
      animal studies were used to estimate the probability of a person developing
      cancer from breathing air containing asbestos fibres in the wider vicinity of the
      mine in order to define appropriate procedures for evaluating asbestos-related
      risk.

PMID- 16889895
TI  - Kinetics of electrodialytic extraction of Pb and soil cations from a slurry of
      contaminated soil fines.
AB  - The objective of this work was to investigate the kinetics of Pb-removal from
      soil fines during electrodialytic remediation in suspension, and study the
      simultaneous dissolution of common soil cations (Al, Ca, Fe, Mg, Mn, Na and K).
      This was done to evaluate the possibilities within control of the remediation
      process to leave a final product suitable for reuse. The Pb-remediation process
      could be divided into four phases: (1) a "lag-phase", (2) a period with a high
      removal rate (7.4 mg/day in average at 40 mA), (3) a period with a low removal
      rate, and (4) a period where no further Pb-removal was obtained. During the first
      phase, dissolution of carbonates was the prevailing process, resulting in a
      corresponding loss of soil mass. During this phase, the investigated ions
      accounted for the major current transfer, while, as remediation proceeded,
      hydrogen ions increasingly dominated the transfer. During phase (3) the high
      conductivity and low voltage suggested that removal may be accelerated by
      increasing the current density. Overall, 97% of the Pb could be extracted,
      reducing the final Pb-concentration to 25 mg/kg. The order of removal rates was:
      Ca>Pb>Mn>Mg>K>(Al and Fe).

PMID- 16889896
TI  - Contribution of the photoperiod at birth to the association between season of
      birth and diurnal preference.
AB  - The aim of the present study was to evaluate the influence of season of birth and
      photoperiod at birth on diurnal preference in young adults. Participants were
      1591 volunteers aged 17-35 years (69% women). The scores obtained on the
      Morningness-Eveningness Questionnaire (MEQ) of Horne and Ostberg were first
      assessed as a function of gender and season of birth by a two-way ANOVA. Results
      revealed a higher MEQ score (reflecting more morningness) in women than in men,
      and in individuals born during autumn than in those born during spring. There was
      no gender-by-season interaction. The MEQ scores of four categories of photoperiod
      at birth were also compared. Individuals born during short photoperiods of 8-10h
      showed stronger morningness than individuals born during photoperiods of 12-14 h.
      The highest morningness scores were observed in subjects born during 8-10h
      photoperiods in the autumn. By contrast, diurnal preference of subjects born
      during 8-10h photoperiods in the winter did not differ from diurnal preference of
      subjects born during longer photoperiods. Our results add support to previous
      reports showing an association between season of birth and morningness
      eveningness, but this association cannot be explained entirely by the length of
      the photoperiod at birth. We suggest that the association between season of birth
      and diurnal preference reflects an influence of light intensity and/or variations
      in photoperiod during early development on the characteristics of the circadian
      system.

PMID- 16889897
TI  - Co-expression of heat shock transcription factors 1 and 2 in rat retinal ganglion
      cells.
AB  - Heat shock protein (HSP) plays an important role in the maintenance of neuronal
      survival during harmful conditions. Previously, we reported that metabolic stress
      induces HSP72 in retinal ganglion cells (RGCs) and protects against
      excitotoxicity, hypoxia and experimental glaucoma. To understand heat shock
      protein transcriptional mechanisms, we examined the cellular expression of heat
      shock factors 1 (HSF1) and 2 (HSF2) in the unstressed adult rat retina. Western
      blotting, immunohistochemistry and RT-PCR showed that mRNA and protein of HSF1
      and HSF2 were present in the rat retina and predominantly expressed in RGC layer
      cells. Western blotting of dissociated RGC suspensions harvested with Thy-1
      immuno-labeled magnetic beads confirmed that RGCs expressed HSF1, HSF2 and HSP72.
      Our findings suggest that both heat shock transcription factors 1 and 2 are
      linked to the heat shock response in retinal ganglion cells.

PMID- 16889898
TI  - Emerging applications for phospho-proteomics in cancer molecular therapeutics.
AB  - Protein phosphorylation is a key mechanism of cell regulation in normal and
      cancer cells. Various new cancer drugs and drug candidates are aimed at protein
      kinase targets. However, selecting patients likely to respond to these
      treatments, even among individuals with tumors expressing validated kinase
      targets remains a major challenge. There exists a need for biomarkers to
      facilitate the monitoring of modulation of drug-targeted kinase pathways. Phospho
      proteomics involves the enrichment of phosphorylated proteins from tissue, and
      the application of technologies such as mass spectrometry (MS) for the
      identification and quantification of protein phosphorylation sites. It has
      potential to provide pharmacodynamic readouts of disease states and cellular drug
      responses in tumor samples, but technical hurdles and bioinformatics challenges
      will need to be addressed.

PMID- 16889899
TI  - The complexity of targeting EGFR signalling in cancer: from expression to
      turnover.
AB  - The epidermal growth factor receptor (ErbB1 or EGFR) has been found to be altered
      in a variety of human cancers. A number of agents targeting these receptors,
      including specific antibodies directed against the ligand-binding domain of the
      receptor and small molecules that inhibit kinase activity are either in clinical
      trials or are already approved for clinical treatment. However, identifying
      patients that are likely to respond to such treatments has been challenging. As a
      consequence, it still remains important to identify additional alterations of the
      tumor cell that contribute to the response to EGFR-targeted agents. While EGFR
      mediated signalling pathways have been well established, there is still a rather
      limited understanding of how intracellular protein-protein interactions,
      ubiquitination, endocytosis and subsequent degradation of EGFR contribute to the
      determination of sensitivity to EGFR targeting agents and are emerging areas of
      investigation. This review primarily focuses on the basic signal transduction
      pathways mediated through activated membrane bound and/or endosomal EGFR and
      emphasizes the need to co-target additional proteins that function either
      upstream or downstream of EGFR to improve cancer therapy.

PMID- 16889900
TI  - Oncological implications of hypoxia inducible factor-1alpha (HIF-1alpha)
      expression.
AB  - Solid tumours contain regions of hypoxia, which may be a prognostic indicator and
      determinant of malignant progression, metastatic development and chemoradio
      resistance. The degree of intra-tumoural hypoxia has been shown to be positively
      correlated with the expression of the transcription factor hypoxia-inducible
      factor 1. HIF-1 is composed of 2 sub-units, namely HIF-1alpha and HIF-1beta. The
      production of hypoxia inducible factor 1-alpha has been identified as a key
      element in allowing cells to adapt and survive in a hostile hypoxic environment
      via a variety of pathways. HIF-1alpha is stabilised by hypoxia at the protein
      level, and also by the oncogenes HER2neu, v-src and ras. There are over 60 target
      genes for HIF-1, many of which are activated in cancers in comparison to
      equivalent normal tissues. Chemotherapeutic modulation of HIF-1 pathways has
      shown promise for patients with chemo-radio resistant or recurrent tumours in
      Phase II clinical trials. We herein review the existing literature on hypoxia
      inducible factor-1alpha, particularly its role in carcinogenesis and clinical
      implications of its over-expression.

PMID- 16889901
TI  - Pharmacological evidence of cholinergic involvement in adult hippocampal
      neurogenesis in rats.
AB  - In adult hippocampus, neural progenitor cells give rise to neurons throughout
      life, and the neurogenesis is modulated by various intrinsic and extrinsic
      factors. Recent reports showed that lesion of septal cholinergic nuclei
      projecting to hippocampus suppressed the survival of newborn cells in the dentate
      gyrus (DG) of hippocampus. Here, we studied whether pharmacological treatment to
      activate or inhibit the cholinergic system could modulate adult hippocampal
      neurogenesis. 5'-Bromo-2'-deoxyuridine (BrdU) was injected to label dividing
      cells before the drug treatment. Immunohistochemical analysis was performed in
      normal rats chronically treated with an acetylcholinesterase inhibitor donepezil
      or a muscarinic acetylcholine receptor blocker scopolamine for four weeks.
      Donepezil increased, but scopolamine decreased, the number of BrdU-positive cells
      in the DG as compared with the control. Neither drug altered the percentage of
      BrdU-positive cells that were also positive for a neuronal marker neuronal
      nuclei, nor net population of proliferative cells labeled with proliferating cell
      nuclear antigen. We also found that donepezil enhanced, and scopolamine
      suppressed, the expression level of phosphorylated cAMP response element binding
      protein (CREB), which is related to cell survival, in the DG. These results
      indicate that donepezil enhances and scopolamine suppresses the survival of
      newborn cells in the DG via CREB signaling without affecting neural progenitor
      cell proliferation and the neuronal differentiation. This is the first evidence
      that pharmacological manipulation of the cholinergic system can modulate adult
      hippocampal neurogenesis.

PMID- 16889902
TI  - Co-expression of the voltage-gated potassium channel Kv1.4 with transient
      receptor potential channels (TRPV1 and TRPV2) and the cannabinoid receptor CB1 in
      rat dorsal root ganglion neurons.
AB  - Potassium channels contribute to basic neuronal excitability and modulation.
      Here, we examined expression patterns of the voltage-gated potassium channel
      Kv1.4, the nociceptive transduction channels TRPV1 and TRPV2 as well as the
      putative anti-nociceptive cannabinoid receptor CB1 by immunofluorescence double
      labelings in sections of rat dorsal root ganglia (DRGs). Kv1.4, TRPV1 and CB1
      were each detected in about one third of neurons (35.7+/-0.5%, 29.4+/-1.1% and
      36.4+/-0.5%, respectively, mean diameter 19.1+/-0.3 microm). TRPV2 was present in
      4.4+/-0.4% of all neurons that were significantly larger in diameter (27.4+/-0.7
      microm; P < 0.001). Antibody double-labeling revealed that the majority of Kv1.4
      positive neurons co-expressed TRPV1 (73.9+/-1.5%) whereas none expressed TRPV2.
      The largest overlap was found with CB1 (93.1+/-0.1%). CB1 expression resembled
      that seen for Kv1.4 since the majority of neurons expressing CB1-protein also
      expressed TRPV1 (69.4+/-6.5%) but not TRPV2 (0.6+/-0.3%). When CB1-mRNA was
      detected using in situ hybridizations an additional subset of larger neurons was
      labeled including 82.4+/-17.7% of the TRPV2 expressing neurons. However, co
      localization of Kv1.4 with CB1-mRNA (92%, mean diameter: 18.5 microm) was
      essentially the same as with CB1-protein. The almost complete overlap of CB1 and
      Kv1.4 in nociceptive DRG neurons suggests a functional synergistic action between
      Kv1.4 and CB1. The potassium channel may have two important roles in nociception.
      As the molecular basis of A-type current it could be involved in the control of
      repetitive discharges at peripheral terminals and as a downstream signal
      transduction site of CB1 in the control of presynaptic transmitter release at
      central terminals.

PMID- 16889903
TI  - Yohimbine may have a therapeutic role in prevention of suicide by regulation of
      glial fibrillary acidic protein expression.

PMID- 16889904
TI  - Correlation of p53 and MIB-1 expression with both the systemic recurrence and
      survival in cases of phyllodes tumors of the breast.
AB  - Phyllodes tumors are rare primary tumors of the breast. The study aimed at
      evaluating the immunohistochemical features of phyllodes tumors of the breast
      that may be useful for predicting the clinical outcome. We examined the
      immunohistochemical expression of the epidermal growth factor receptor (EGFR),
      HER2/neu, CD117/c-kit, p53, and MIB-1, and analyzed correlations between the
      immunohistochemical findings and the clinical outcome. The study included 41
      patients with phyllodes tumor (20 benign, 5 borderline, and 16 malignant).
      Systemic recurrence occurred in 9 patients. The 2-year survival rate was 84%, and
      the 2-year recurrence-free survival rate was 77%. Six patients developed systemic
      recurrence within the first year after surgery. None of the phyllodes tumors was
      positive for HER2/neu or CD117/c-kit. Positive staining for p53 was seen in 10
      phyllodes tumors (24%), and the median MIB-1 index was 10%. Both p53 expression
      and the MIB-1 index, but not the expression status of EGFR, were significantly
      correlated with the recurrence-free and overall survival. p53 expression status
      and MIB-1 index may be significant prognostic factors in patients with phyllodes
      tumors, and careful postoperative follow-up may be important in those cases
      showing positive expression of p53 and/or MIB-1 index.

PMID- 16889905
TI  - Insecticide and antifeedant activity of different plant parts of Melia azedarach
      on Xanthogaleruca luteola.
AB  - In laboratory choice and no-choice bioassays, treatment of elm leaves with
      extracts obtained from unripe fruits and green or senescent leaves of Melia
      azedarach at 1-10% concentration significantly deterred feeding by adults of the
      elm leaf beetle, Xanthogaleruca luteola. Also, in no-choice tests, adults fed on
      leaves treated with 2, 5 or 10% extract showed a dramatic increase in mortality
      rates. Extracts from the different plant structures were similarly active, and
      starvation as a consequence of their strong antifeedant activity could play a
      significant role in the high mortality values observed.

PMID- 16889906
TI  - Effect of Satureja khuzestanica essential oil on male rat fertility.
AB  - This study was undertaken to study the effect of Satureja khuzestanica essential
      oil (SKEO) in male rat fertility. SKEO was administered orally at doses of 75,
      150, and 225 mg/kg/day for 45 days through drinking water. Treated and control
      rats were mated with female on day 45 of treatment. SKEO significantly improved
      all the parameters evaluated such as potency, fecundity, fertility index, and
      litter size. Moreover, concentrations of FSH and testosterone were significantly
      increased in SKEO-treated groups. Also the weights of testes, seminal vesicles,
      and ventral prostate weights were increased by SKEO (225 mg/kg).
      Histopathological analysis showed that in male rats treated with SKEO (150, 225
      mg/kg) the number of spermatogonium, spermatid cords, Leydig cells, and
      spermatozoids was increased. Also in these groups, the Sertoli cells were
      hypertrophic.

PMID- 16889907
TI  - Effects of Butea superba on reproductive systems of rats.
AB  - The effects of Butea superba on the reproductive system in male Wistar rats were
      investigated. The animals were fed daily with the powdered crude drug suspended
      in distilled water by a gastric tube at the dose of 2, 25, 250 and 1250 mg/kg
      body weight for 8 weeks. Rats fed with 1 ml of distilled water were used as a
      negative control. The weights of all vital organs in all treated groups were not
      different from the control. The percentage weight ratios of body weights of
      seminal vesicles and prostate glands were not different from the control, except
      that the testis of the group fed with 1250 mg/kg was significantly different from
      the control and the other treated groups. In addition, the sperm counts in this
      group showed about 16% more than the control group. Hematology as well as the
      liver and kidney function of all treated groups showed no difference from the
      control. B. superba, drug at 250 mg/kg which was 100 times more than the Thai FDA
      recommended dose for humans appeared to be safe in rats. The crude drug has
      demonstrated an increase tendency on testis weight and sperm counts in rat. The
      information from the present study can be used to explain the Thai folklore
      application of this plant in Thailand.

PMID- 16889908
TI  - Polymorphic microsatellite sites in the PRNP region point to excess of
      homozygotes in Creutzfeldt-Jakob disease patients.
AB  - Polymorphic microsatellite sites within 148 kb of the human prion gene complex,
      including the genes PRNP, PRND and PRNT, were analysed together with the Codon129
      variants regarding 50 CJD (Creutzfeldt-Jakob Disease) patients and 46 non
      diseased control persons. Three of the sites (MM03, MM04, Codon129) differed
      significantly (P<0.05) for their allele frequencies between the two groups--the
      predominant allele being always more frequent in the CJD group. Deviations from
      Hardy-Weinberg Equilibrium were mainly obtained in the CJD group--in all cases
      with a reduction of the observed heterozygosity. The sites MM03, MM04 and
      Codon129 were also analysed for their haplotypes. The predominant homozygous
      haplotype combination was more frequently observed in the CJD group (0.875) than
      in the non-diseased group (0.38). Thus the different polymorphic sites indicate
      that high CJD disposition is associated with homozygosity in the PRNP gene.

PMID- 16889909
TI  - Effect of follicular size on in vitro developmental competence of oocytes and
      viability of embryos after transfer in the dromedary (Camelus dromedarius).
AB  - The aim of this work was to determine the effect of follicle size on camel oocyte
      quality as measured by developmental competence in vitro and in vivo. Ovaries
      from a local slaughterhouse were dissected to obtain two classes of follicle
      size: small (3-6 mm) and large (>6 mm) follicles. Quality of the oocytes was
      assessed after in vitro maturation (IVM), in vitro fertilization (IVF) and in
      vitro culture (IVC) of cumulus oocyte complexes (COCs). All cultures were done in
      four replicates at 38.5 degrees C, under 5% CO(2) and high humidity (>95%). Only
      COCs with cumulus and homogenous (dark) cytoplasm were used. The COCs were
      matured for 28 h in TCM-199 medium supplemented with 10% heat-treated fetal calf
      serum (FCS), 10 ng/mL EGF, and 250 microM cysteamine. Nuclear maturation rate for
      each class of follicle size was determined by contrast phase microscopy in a
      sample of COCs (n=30) denuded, fixed and stained with aceto-orcein. In vitro
      fertilization was performed using fresh semen (0.5 x 10(6)spermatozoa/mL in
      modified TALP-solution). Fertilized oocytes were cultured in mKSOMaa, under 5%
      O(2) and 90% N(2). The percentage of COCs reaching metaphase II (MII) after 28 h
      of maturation was 87% (26/30) and 73% (22/30) for oocytes originating from large
      and small follicles, respectively (P>0.1). The rate of total cleavage (two cells
      to blastocyst stage) was greater (P<0.05) for oocytes originating from large
      follicles (72%; 116/162) than for those derived from small follicles (59%;
      140/237). The percentage of fertilized oocytes reaching the blastocyst stage was
      35% (57/162) and 20% (48/237) for oocytes collected from large and small
      follicles, respectively (P<0.05). The viability of in vitro-produced hatched
      blastocyst from the two groups (15 from 3 to 6mm follicle size and 22 from
      follicles >6 mm) was assessed by transfer to synchronized recipients. None of the
      hatched blastocysts from small follicles resulted in a pregnancy whereas 68%
      (15/22) of the transferred hatched embryos from large follicles developed into a
      25-day pregnancy. Of the resulting 15 pregnancies, 53% (n=8) aborted (five
      between 2 and 4 months and three between 5 and 7 months of pregnancy). The
      remaining seven pregnant females gave birth to normal healthy offsprings (four
      females and three males). The present study shows that dromedary oocytes
      developmental competence is acquired late during the final phase of follicular
      development and this developmental ability translates into greater pregnancy
      rates after transfer of in vitro produced hatched blastocysts.

PMID- 16889910
TI  - Effects of Zeranol upon luteal maintenance and fetal development in peripubertal
      gilts.
AB  - Eighty gilts were utilized to determine whether zeranol implants could maintain
      hCG-induced corpora lutea (CL) in peripubertal gilts and to examine the effects
      of a Zeranol implant on fetal development. Crossbred gilts (171+/-0.3 days of
      age, 109.1+1.4 kg) were blocked by weight and ancestry to control (n=40) or
      treatment (n=40) groups. To induce ovulation and CL maintenance, treated gilts
      received 500 IU of hCG i.m. and a Zeranol ear implant (Ralgro, 36 mg; day 0). All
      gilts were checked once daily for estrus with a mature boar from days 3-58 of the
      experiment. On day 42, treated gilts received two 10 mg injections of Lutalyse
      (PGF(2)alpha) spaced 6 h apart. Treated gilts not displaying estrus within 7 days
      of PGF(2)alpha received two additional 10 mg of PGF(2)alpha spaced 6 h apart on
      day 49. On days 44-58, gilts detected in estrus were inseminated twice, 24 h
      apart with pooled semen via AI. Blood samples were obtained on days 0, 7, 18 and
      42 and analyzed for serum progesterone (P(4)). Bred gilts were slaughtered on
      days 58-62 of gestation. Ovulation, as determined by serum concentrations of P(4)
      on day 7 of the experiment, was induced by hCG in 79.5% of treated gilts. Zeranol
      implants, however, failed to increase (P>0.05) the proportion of gilts available
      for breeding (treated, 21/39; control, 18/40). Of gilts inseminated on days 44
      58, 16/21 treated gilts and 16/18 control gilts were pregnant at slaughter on
      days 58-62 of gestation. Number of fetuses (7.5 versus 12), fetal weight (83
      versus 121 g), fetal length (117 versus 132 mm) and fetal survival (45% versus
      78%) were reduced (P<0.001) by Zeranol implants. These data indicate that
      treatment of peripubertal gilts with a 36 mg Zeranol implant did not increase the
      proportion of gilts available for breeding while causing deleterious effects upon
      the fetuses.

PMID- 16889911
TI  - Effect of different procedures of ejaculate collection, extenders and packages on
      DNA integrity of boar spermatozoa following freezing-thawing.
AB  - Whole ejaculate or sperm-rich fraction, collected from four sexually mature
      boars, was frozen in an extender containing lactose-hen egg yolk with glycerol
      (lactose-HEY-G) or extender containing lactose, lyophilized lipoprotein fractions
      isolated from ostrich egg yolk and glycerol (lactose-LPFo-G), and Orvus Es Paste,
      respectively. The sperm samples were also frozen in a standard boar semen
      extender (Kortowo-3), without the addition of cryoprotective substances. Sperm
      DNA integrity was assessed using a modified neutral comet assay. Sperm
      characteristics such as motility, plasma membrane integrity (SYBR-14/PI),
      mitochondrial function (rhodamine 123) and acrosome integrity were monitored.
      Freezing-thawing caused a significant increase (P<0.05) in sperm DNA
      fragmentation, irrespective of the procedures of ejaculate collection and
      extender type. Sperm DNA fragmentation was significantly lower (P<0.05) in the
      whole ejaculate compared with the sperm-rich fraction, indicating that
      spermatozoa maintained in the whole seminal plasma prior to its removal for
      freezing-thawing procedure were less vulnerable to cryo-induced DNA
      fragmentation. Furthermore, spermatozoa frozen in lactose-HEY-G or lactose-LPFo-G
      extender exhibited lower (P<0.05) DNA fragmentation than those frozen in the
      absence of cryoprotective substances. The levels of sperm DNA damage, as
      expressed by comet tail length and tail moment values, were significantly higher
      (P<0.05) in sperm samples frozen in the absence of cryoprotective substances. The
      deterioration in post-thaw sperm DNA integrity was concurrent with reduced sperm
      characteristics. It can be suggested that evaluation of DNA integrity, coupled
      with different sperm characteristics such as motility, plasma membrane integrity
      and mitochondrial function, may aid in determining the quality of frozen-thawed
      boar semen.

PMID- 16889912
TI  - Clinical guidelines for improving compliance with hormone therapy in Latin
      American women during the menopausal transition and thereafter.
AB  - OBJECTIVE: To provide uniform, objective guidance for physicians and other health
      care workers in Latin America to enhance compliance with hormone therapy (HT),
      and to provide a tool for continued medical education and a source for answering
      clinical questions. METHOD: Literature search using MEDLINE; identification of
      key relevant publications by a five-member expert committee; creation and
      validation of a 60-item questionnaire used to survey the opinion of 72 physicians
      participating in a Latin American symposium, "The Faces of Menopause". RESULTS:
      On the basis of the validated responses, major points were identified to enhance
      compliance with HT with specific reference to Latin America, and two algorithms
      were created to provide practical guidance. CONCLUSION: The present guidelines
      will facilitate optimal compliance with therapy in Latin American postmenopausal
      women who opt for HT and for whom HT is indicated.

PMID- 16889913
TI  - Dexamethasone nano-aggregates composed of PEG-PLA-PEG triblock copolymers for
      anti-proliferation of smooth muscle cells.
AB  - Dexamethasone nano-aggregate was prepared for the treatment of intimal
      hyperplasia caused by abnormal proliferation of smooth muscle cells. Triblock
      copolymers composed of poly(ethylene glycol) [PEG] and poly(D,L-lactic acid)
      [PLA] were synthesized with different chain lengths of PEG. Triblock copolymers
      in organic phase were mixed with dexamethasone and dexamethasone nano-aggregates
      was prepared by dispersing the organic phase into water. The average diameter of
      the nano-aggregates ranged from 200 to 300 nm. Dexamethasone was released out
      from the nano-aggregates and the release profile was dependent on PEG chain
      lengths. The dexamethasone nano-aggregates showed superior anti-proliferation
      effects on smooth muscle cells compared to dexamethasone. Flow cytometry showed
      that smooth muscle cells treated with dexamethasone nano-aggregates was arrested
      at a dormant phase in a dose-dependent manner. The dexamethasone nano-aggregates
      are expected to be a potent candidate for anti-proliferating smooth muscle
      tissues after a balloon-catheter treatment.

PMID- 16889915
TI  - Monitoring small molecule diffusion into hydrogels at various temperatures by
      fluorescence technique.
AB  - Steady state fluorescence technique was used to study small molecule diffusion
      into polyacrylamide (PAAm) gels at various temperatures. Pyranine (P(y)),
      dissolved in water was introduced as a probe and fluorescence emission (I(p))
      from P(y) was monitored during diffusion. Scattered light intensities, I(sc) from
      PAAm gel was also monitored to observe structural variations during diffusion
      process. Increase in I(p) intensity was attributed to P(y) diffusion into PAAm
      gel. On the other hand decrease in I(sc) intensity was interpreted as the
      variation of the spatial heterogeneities in the system. Li-Tanaka and Fickian
      models were used to quantify the swelling and diffusion experiments and diffusion
      coefficients were produced in both cases. Related activation energies were also
      calculated from the corresponding physical processes.

PMID- 16889914
TI  - Sodium pantoprazole-loaded enteric microparticles prepared by spray drying:
      effect of the scale of production and process validation.
AB  - Pantoprazole is a prodrug used in the treatment of acid related disorders and
      Helicobacter pylori infections. It is activated inside gastric parietal cells
      binding irreversibly to the H(+)/K(+)-ATPase. In this way, pantoprazole must be
      absorbed intact in the intestinal tract, which indicates that enteric drug
      delivery systems are required for its oral administration. The purpose of this
      study was to investigate the physical characteristics of enteric pantoprazole
      loaded microparticles prepared by spray drying using a blend of Eudragit S100 and
      HPMC. The microparticles were produced in different spray dryers and operational
      conditions at laboratory and pilot scales. Microparticles produced with two fluid
      nozzle atomizer and air pressure of 196 kPa presented satisfactory encapsulation
      efficiency and gastro-resistance. Microparticles produced with the same atomizer
      but using 49 kPa of air pressure presented strings in the powder. The
      microparticles produced in mixed flow presented very high polydispersity and the
      ones produced with rotating disc atomizer presented drug crystals adsorbed on the
      particle surfaces. The microparticles produced with two fluid nozzle atomizer and
      196 kPa were prepared in three consecutive days for the process validation. The
      powders showed reproducible diameter, polydispersity, densities, encapsulation
      efficiency and gastro-resistance profile.

PMID- 16889916
TI  - Synthesis and properties of cordycepin intercalates of Mg-Al-nitrate layered
      double hydroxides.
AB  - Layered double hydroxides (LDHs) were investigated as cordycepin delivery
      nanocarriers for the first time in this study. Negatively charged biomolecule
      cordycepin was intercalated in the gallery spaces of [Mg-Al-NO(3)] as the charge
      compensating species, which was confirmed by the results of XRD, FT-IR, TEM, CZE
      and electrophoretic mobility. Cell experiment suggested that the new bio-LDH
      nanohybrid could prevent cordycepin decomposition by adenosine deaminase. This
      new formulation could possibly be used as a novel form cordycepin intravenous
      injection.

PMID- 16889917
TI  - Ryanodine receptor localisation in the mammalian cochlea: an ultrastructural
      study.
AB  - Calcium-induced calcium release (CICR) in the mammalian cochlea has been
      suggested to enhance neurotransmitter release from inner hair cells and
      facilitate the efferent response in outer hair cells. Light microscopic evidence
      exists for the presence of ryanodine receptors in the organ of Corti but there is
      so far no information about their ultrastructural localisation. We have therefore
      used post-embedding immunogold labeling with antibodies that predominantly
      recognise ryanodine receptor isoforms 1 (RyR1) and 2 (RyR2) to investigate their
      distribution in rat cochleae. In inner hair cells, the highest levels of labeling
      were observed over an area of rough endoplasmic reticulum that lies in the
      cytoplasmic region beneath the nucleus; in outer hair cells, the cytoplasmic
      region above the nucleus displayed most labeling. Labeling was also associated
      with the subsurface cisternae adjacent to the lateral membranes of both types of
      hair cell, with the efferent terminals on the outer hair cells and was observed
      in adjacent supporting cells. Labeling in outer hair cells was significantly
      higher than that in inner hair cells or in the supporting cells. Our results
      support the presence of RyR1 in the cochlea but do not rule out the presence of
      other isoforms. CICR may be involved in the control of calcium levels in the base
      of the inner hair cells and supporting cells, and in the cholinergic efferent
      response and motile behaviour of the outer hair cells.

PMID- 16889919
TI  - Sugar and fatty acid analysis in ecstasy tablets.
AB  - Sugars and stearates (composed of fatty acids) are both frequent components used
      in the production of ecstasy tablets. Their analysis can therefore provide
      supplementary information useful for drug intelligence. Links established using
      these substances would be very significant as they should give us information
      about the manufacturer of the tablets. Two methods have been developed for the
      analysis of sugars and fatty acids by GC-MS and were applied to 109 ecstasy
      tablets. Characterisation of the samples should allow the differentiation of a
      certain number of them and furthermore their classification into groups. This is
      obtained by analysing the raw data using chemometric methods. Several pre
      treatments have been tested together with six similarity measures on a small
      number of ecstasy samples in order to determine which combination would best
      characterise one ecstasy sample and differentiate it from the others at the same
      time. Normalisation followed by the fourth square and applied together with the
      squared cosine function appeared to give the best results and has been applied to
      all samples. The correlation values obtained of each sample with all others
      express the probability of a presence of a link between two samples. In order to
      verify the signification of these values, and thus of a link, all samples have
      been compared considering the data visually according to three selected
      criterions. The 109 examined samples could be divided into 67 groups, with 43 of
      them containing only one sample. Considering the distribution of their
      correlation values, sample pairs showing a value below 0.23 can be considered as
      linked. As the excipients are necessarily related to the blending, which also
      includes the active substance, and variation in the excipient content has been
      proven by the grouping of the samples, a low similarity value does indicate a
      link with regard to the producer. In conclusion, it appears that the result
      obtained with the excipients is certainly very valuable, but all other available
      information has to be taken into account as well before making any conclusions.

PMID- 16889918
TI  - Protective effect of Lygodium flexuosum (L.) Sw. extract against carbon
      tetrachloride-induced acute liver injury in rats.
AB  - The hepatoprotective potential of Lygodium flexuosum (L.) Sw. was evaluated in
      male Wistar rats against carbon tetrachloride-induced liver damage in preventive
      and curative models. Toxic control and n-hexane extract-treated rats received a
      single dose of CCl4 (150 microL/100g, 1:1 in corn oil). Pre-treated rats were
      given n-hexane extracts at 200 and 100 mg/kg dose 48, 24 and 2 h prior to CCl4
      administration. In post-treatment groups, rats were treated with n-hexane extract
      at a dose of 200 and 100 mg/kg, 2, 24 and 48 h after CCl4 intoxication. Rats pre
      treated with Lygodium flexuosum remarkably prevented the elevation of serum AST,
      ALT, LDH and liver lipid peroxides in CCl4-treated rats. Rats treated with the
      extract after the establishment of CCl4 induced liver injury showed significant
      (p < or = 0.05) protection of liver as evidenced from normal AST, ALT, LDH and
      MDA levels. Hepatic glutathione levels were significantly (p < or = 0.05)
      increased by the treatment with the extracts in both the experimental groups.
      Histopathological changes induced by CCl4 were also significantly (p < or = 0.05)
      reduced by the extract treatment in preventive and curative groups. Phytochemical
      studies revealed the presence of saponins, triterpenes, sterols and bitter
      principles in Lygodium flexuosumn-hexane extract which could be responsible for
      the possible hepatoprotective action.

PMID- 16889921
TI  - The difference between drug money and a "lifetime's savings".
AB  - In many countries, monies suspected of being associated with drug trafficking can
      be seized by the authorities. One of the ways of investigating this association
      is through the analysis of seized banknotes for traces of controlled drugs. We
      report three studies which may assist the expert in assessing whether banknotes
      contaminated with diamorphine are part of the general population of notes in
      circulation or whether they show unusual contamination patterns which require
      explanation. Study 1 is based on three plausible contamination scenarios as they
      may occur during the various stages of an illicit drug transaction and seizure.
      It shows that notes which have been in direct contact with visible traces of
      diamorphine show significantly higher contamination to those in more indirect
      contact with the drug. Study 2 investigates the transfer of diamorphine from one
      highly contaminated note to other notes in a bundle over a period of 10 weeks
      with and without agitation. It was found that the total amount of drug
      transferred was smaller than 6% and no more than 4 out of a bundle of 10
      previously clean notes became lightly contaminated. Based on extensive background
      data, study 3 proposes a probabilistic model to assess whether an observed
      proportion of diamorphine bearing banknotes is likely to have been contaminated
      by chance. The model predicts that there is only a 0.3% chance that a bundle of
      100 notes from the general banknote population contains more than six
      contaminated specimens. Jointly, the three studies give useful indications for
      the spread of contamination throughout a sample and the amounts of heroin which
      may be expected given plausible contamination scenarios.

PMID- 16889920
TI  - Clothing damage analysis in alleged sexual assaults--the need for a systematic
      approach.
AB  - Clothing damage analysis is an integral part of the examinations carried out in
      sexual assault type cases. This analysis can be used to corroborate different
      versions of events and is at its most powerful in elucidating false allegation
      cases and consent cases. The purpose of this study was to determine to what
      extent people with varying levels of forensic awareness, experience and training
      could correctly carry out damage analysis. Two participant groups were asked to
      take part in this study. Group A ('forensic group') comprised participants at a
      forensic science conference, and Group B ('student group') comprised students
      undertaking a degree course in Forensic Science. Each group was given a practical
      workshop consisting of a lecture outlining common fabric types and general
      features observed in different damage types. Each participant was subsequently
      shown 25 pieces of 'damage' and asked to identify both the type of fabric
      construction (knit or weave) and the type of damage (cut, tear, rip, wear and
      tear). The ability to identify fabric construction and damage types varied within
      the two groups studied and across the groups. The forensic group performed better
      both in fabric and damage assessment than the student group. This paper suggests
      a systematic approach to clothing damage analysis to maximise the benefits that
      can be obtained from this area of forensic science and to minimise the
      subjectivity within the field.

PMID- 16889922
TI  - Influence of rubber compound and tread pattern of retreaded tyres on vehicle
      active safety.
AB  - The aim of the article is to present the results of road tests of original and
      retreaded tyres, analysed in the aspect of vehicle active safety. The tests
      covered emergency braking, steady-state circular tests and severe lane-change
      manoeuvre. The tests were performed in summer and winter conditions. Original
      Michelin tyres and Michelin tyres retreaded with summer and winter rubber
      compounds were used. The results of the tests proved that vehicle active safety
      is affected by retreaded tyres. The differences between braking deceleration of a
      car with original tyres and braking deceleration of a car with retreaded tyres
      confirmed the necessity of performing braking tests on the place of accident with
      the set of tyres with which the vehicle participating in the accident was
      equipped.

PMID- 16889923
TI  - Neck dissection: then and now.
AB  - The significance of metastatic disease in the lymph nodes of the neck as a
      critical independent prognostic factor in head and neck cancer has long been
      appreciated. Although 19th century surgeons attempted to remove involved cervical
      lymph nodes at the time of resection of the primary cancer, a systematic approach
      to en bloc removal of cervical lymph node disease, described in detail by
      Jawdynski in 1888 and popularized and illustrated by Crile in the early 20th
      century, provided consistent and more effective treatment, and forms the basis of
      our current techniques. During the first half of the 20th century, developments
      included preservation of the accessory nerve in selected cases, elective neck
      dissection performed in association with resection of various primary tumors,
      bilateral neck dissection and limited neck dissection. The greatest impetus to
      the status of radical neck dissection came from Martin, whose technique consisted
      of resection of all lymph nodes from level I-V together with the accessory nerve,
      internal jugular vein, sternocleidomastoid muscle and various other structures in
      a single block of resected tissue. Martin's technical precepts were followed
      until the latter part of the 20th century when modifications in technique began
      to find general acceptance. The first description of an effective technique of
      modified radical neck dissection was published in Spanish by Suarez, in 1963.
      This technique, which preserves important structures, such as the internal
      jugular vein, sternocleidomastoid muscle and accessory nerve, was refined and
      popularized by various authors who published their results in the English
      language literature during the period from 1964 through 1990 and beyond. Modified
      or "functional" neck dissection avoids much of the morbidity of radical neck
      dissection while achieving equivalent degrees of control of regional disease in
      properly selected cases. By the late 20th century, the concept of selective neck
      dissection, consisting of resection of only the nodal groups at greatest risk for
      metastasis from a given primary site, was studied and developed. These limited
      dissections are now widely employed for elective, and in properly selected cases,
      therapeutic treatment and staging of the neck, and have been proposed for limited
      cervical recurrences after various chemoradiation protocols. Prospective studies
      have demonstrated similar rates of neck recurrence and survival after elective
      selective neck dissection compared to elective modified radical neck dissection.
      Other modifications and factors applied to treatment of cervical lymph node
      disease include the use of adjuvant and neo-adjuvant radiation and chemotherapy,
      a revised system for classification of neck dissections, the identification of
      various adverse prognostic factors such as extracapsular spread and extranodal
      soft tissue deposits, application of sentinel lymph node biopsy to staging of the
      neck, the use of immunohistochemical and molecular techniques for identification
      of lymph node metastases not detectable by light microscopy, and the possibility
      of endoscopic neck dissection. The authors conclude that neck dissection, as
      evolved over the past century, is a fundamental tool in management of patients
      with head and neck cancer, but is still a work in progress.

PMID- 16889925
TI  - Assessment of survival of aging erythrocyte in circulation and attendant changes
      in size and CD147 expression by a novel two step biotinylation method.
AB  - Three intravenous injections (1mg each) of biotin-X-NHS (BXN) given at 24h
      intervals labeled all circulating erythrocytes with biotin in C57Bl/6 mice. After
      5 days, administration of another i.v. injection of BXN (0.6mg) resulted in the
      labeling of erythrocytes released in blood circulation after the first
      biotinylation step, with a lower intensity of biotin. The older erythrocyte
      population with high intensity of biotin (biotin(high) population) and the later
      population of newly formed erythrocytes with lower intensity of biotin
      (biotin(low) population) could be stained with streptavidin-APC (SAv) and
      identified by flow cytometry. Using the double biotinylation technique, we could
      examine the survival and age related changes in biotin(low) population of
      erythrocytes that was released in circulation during a defined time period (5
      days). Our results indicate that the percentage of Biotin(low) erythrocytes in
      circulation remained static for 10 days after the second biotinylation step and
      than started to decline steadily with time. Mean fluorescence intensity of biotin
      label on surviving biotin(low) population of erythrocytes however remained
      stable. These results suggest that after 15 days of release in blood,
      erythrocytes may undergo random destruction. Furthermore, forward scatter as well
      as CD147 expression of Biotin(low) population also declined with age. Double
      biotinylation technique described in this communication offers an easy method for
      tracking age related changes in populations of erythrocytes released in
      circulation during a defined period of time.

PMID- 16889924
TI  - Genetic and molecular characterization of CLK-1/mCLK1, a conserved determinant of
      the rate of aging.
AB  - The clk-1 gene of the nematode Caenorhabditis elegans encodes an evolutionarily
      conserved enzyme that is necessary for ubiquinone biosynthesis. Loss-of-function
      mutations in clk-1, as well as in its mouse orthologue mclk1, increase lifespan
      in both organisms. In nematodes, clk-1 extends lifespan by a mechanism that is
      distinct from the insulin signaling-like pathway but might have similarities to
      calorie restriction. The evolutionary conservation of the effect of clk-1/mclk1
      on lifespan suggests that the gene affects a fundamental mechanism of aging. The
      clk-1/mclk1 system could allow for the understanding of this mechanism by
      combining genetic and molecular investigations in worms with studies in mice,
      where age-dependent disease processes relevant to human health can be modeled.

PMID- 16889926
TI  - The imaging features of gastrointestinal stromal tumours.
AB  - Gastrointestinal stromal tumours (GISTs) are a rare group of mesenchymal
      neoplasms that occur predominantly in the gastrointestinal tract. Previously
      GISTs were classified as smooth muscle tumours referred to as leiomyomas,
      leiomyosacromas or leiomyoblastomas. However, with the advent of
      immunohistochemistry, GISTs are now defined by the identification of cKit
      positivity. This is now used to select patients with metastatic disease who may
      respond to chemotherapeutic agents such as the tyrosine kinase inhibitor, STI
      571. In this pictorial essay we have attemped to describe the range of imaging
      findings of GISTs that can suggest a pre-biopsy diagnosis.

PMID- 16889927
TI  - [Does age influence admission intensive care after medicalized prehospital
      management?].

PMID- 16889928
TI  - Protection by rhamnose-rich polysaccharides against the cytotoxicity of Maillard
      reaction products.
AB  - Previous experiments have shown that AGE-products added to human skin fibroblast
      cultures increased the number of dead cells floating on top of the culture fluid
      and took up vital dye [1]. In these experiments, we tested several rhamnose-rich
      polysaccharides for protection against the cytotoxic effect of AGE-s. Added at
      relatively low concentrations (between 10 and 100 microg/ml) to the culture
      medium, several of the tested rhamnose-rich oligo- and polysaccharides (RROP-s)
      gave a significant protection against AGE-induced cytotoxicity. Their effect on
      cell proliferation was also tested. The number of cells at saturation density was
      also shown to be influenced by AGE-products added to the cultures. This effect
      was also, at least partially, corrected by the rhamnose-rich oligo- and
      polysaccharides. These substances might therefore be considered as of potential
      therapeutical interest against hyperglycemia induced cytotoxic effects as in type
      II-diabetes.

PMID- 16889929
TI  - Cytotoxic activity of violacein in human colon cancer cells.
AB  - Several studies have shown that violacein, a purple pigment extracted from
      Chromobacterium violaceum, is capable to induce apoptosis in a variety of cancer
      cells, including those leukemia cell lines. Herein, we examined the effects of
      violacein on reactive oxygen species (ROS) production during the apoptotic colon
      cancer cell death. We demonstrate that violacein mediates ROS production followed
      by activation of Caspase-3, release of cytochrome c, and calcium release to
      citosol in Caco-2 cells. Moreover, presence of ROS scavengers such as N-acetyl
      cysteine (NAC) diminishes ROS cytotoxicity induced by violacein in Caco-2 cells,
      indicating that violacein mediates cellular critical mechanisms in the triggering
      of apoptotic tumor cell death. These data also imply that violacein-induced ROS
      are collectively key mediators of mitochondrial membrane collapse, leading to
      cytochrome c release, and culminating in tumor apoptosis. Unlike in Caco-2 cells,
      violacein was incapable of increasing ROS levels in HT29 cells, suggesting the
      existence of violacein cell-type specific mechanisms. Those findings bring light
      to the violacein cytotoxic mechanism studies, indicating that oxidative stress
      play a role in the violacein-induced cytotoxicity.

PMID- 16889930
TI  - Victoria Symptom Validity Test performance in acute severe traumatic brain
      injury: implications for test interpretation.
AB  - Effort testing has become commonplace in clinical practice. Recent research has
      shown that performance on effort tests is highly correlated with performance on
      neuropsychological measures. Clinical application of effort testing is highly
      dependent on research derived interpretive guidelines. The Victoria Symptom
      Validity Test (VSVT) is one of many measures currently used in clinical practice.
      The VSVT has recommended interpretive guidelines published in the test manual,
      but the samples used in developing interpretive guidelines are small and
      heterogeneous and concern has been expressed regarding high false negative rates.
      In this study, a homogeneous sample of acute, severely brain injured persons were
      used to assess the sensitivity of the VSVT. Results confirmed that acute,
      severely brain injured persons (N=71) perform very well on the VSVT. The severe
      brain injury population is 99% likely to have between 44.1 and 46.8 correct VSVT
      Combined Score responses. While the VSVT was insensitive to memory dysfunction,
      the presence of severe visual perceptual (Benton Visual Form Discrimination
      Score<21) and verbal fluency (Controlled Oral Word Association Score<15) deficits
      predicted poor performance on the VSVT. These results provide further evidence
      that performance expectations currently incorporated in the VSVT manual
      interpretative criteria are too conservative. Empirically based alternative
      criteria for interpreting VSVT Combined Scores in the TBI population are
      presented.

PMID- 16889931
TI  - Anxiety Sensitivity Amelioration Training (ASAT): a longitudinal primary
      prevention program targeting cognitive vulnerability.
AB  - Fear of arousal symptoms, often referred to as anxiety sensitivity (AS) appears
      to be associated with risk for anxiety pathology and other Axis I conditions.
      Findings from a longitudinal prevention program targeting AS are reported.
      Participants (n=404) scoring high on the Anxiety Sensitivity Index (ASI) were
      randomly assigned to receive a brief intervention designed to reduce AS (Anxiety
      Sensitivity Amelioration Training (ASAT)) or a control condition. Participants
      were followed for up to 24 months. Findings indicate that ASAT produced greater
      reductions in ASI levels compared with the control condition. Moreover,
      reductions were specific to anxiety sensitivity relative to related cognitive
      risk factors for anxiety. ASAT also produced decreased subjective fear responding
      to a 20% CO(2) challenge delivered postintervention. Data from the follow-up
      period show a lower incidence of Axis I diagnoses in the treated condition though
      the overall group difference was not statistically different at all follow-up
      intervals. Overall, findings are promising for the preventative efficacy of a
      brief, computer-based intervention designed to decrease anxiety sensitivity.

PMID- 16889932
TI  - Carbohydrate consumption during cycling increases in vitro NK cell responses to
      IL-2 and IFN-gamma.
AB  - INTRODUCTION: Exercise has been shown to lower blood natural killer cell
      concentration and activity for up to 24-h after exercise; however, the mechanism
      underlying this effect is not clearly defined. We have speculated that an
      exercise-induced change in T-cell control of NK cells is at least partly
      responsible for the post-exercise suppression. As a follow-up to our previous
      research, the purpose of this study was to examine the T and NK cells responses
      during and following moderate/high-intensity endurance exercise. METHODS: Eight
      male subjects (20+/-1 y; VO(2peak)=67.22+/-2.79 mL.kg(-1).mL(-1)) were recruited
      to complete two 1-h (75-80% VO(2peak)) cycling trials in a random counterbalanced
      order: carbohydrate (CHO) and placebo (PLA). Venous blood samples were collected
      before (PRE), immediately (POST), 2-h (2H), and 4-h (4H) after exercise. NK (CD3(
      )/56(+)) and activated NK (CD3(-)/56(+)/69(+)) number were measured using flow
      cytometry. NK cell activity (NKCA) was determined using both a (51)Cr release
      assay (NKCA-51) and activated NK cell number (NKCA-69). Whole blood samples were
      stimulated with IL-2, IFN-gamma, IL-4, IL-12, and no stimulation for 12-h and
      then analyzed for NK cell activity using a (51)Cr release assay (NKCA-51).
      RESULTS: Leukocyte counts and unstimulated NKCA were not different between CHO
      and PLA; however, exercise significantly increased NKCA (P<.05). Fold change in
      IL-2, IFN-gamma, and IL-2+IFN-gamma-stimulated NKCA were significantly greater in
      CHO compared to PLA (P<.05). No effect of drink was found for IL-4, IL-12, and IL
      4+IL-12-stimulated NKCA. DISCUSSION: The fold change in IL-2-stimulated NKCA is
      consistant with our previous published work. The drink effect for Th1 (but not
      Th2) cytokines suggests they may play a more significant role in modulating NKCA
      following a strenuous bout of aerobic exercise when CHO is consumed.

PMID- 16889933
TI  - Can children with (central) auditory processing disorders ignore irrelevant
      sounds?
AB  - This study investigated the effects of irrelevant sounds on the serial recall
      performance of visually presented digits in a sample of children diagnosed with
      (central) auditory processing disorders [(C)APD] and age- and span-matched
      control groups. The irrelevant sounds used were samples of tones and speech.
      Memory performance was significantly disrupted in the presence of irrelevant
      sounds in all three groups of children. While irrelevant speech was more
      disruptive than irrelevant tones in the two control groups, children diagnosed
      with (C)APD did not show larger disruption from irrelevant speech compared to
      irrelevant tones. Children diagnosed with (C)APD appear to process speech
      differently from their typically developing peers, and this may be remediated
      with auditory training procedures and the placement of these children in smaller
      classes.

PMID- 16889934
TI  - Using the Natural Language Paradigm (NLP) to increase vocalizations of older
      adults with cognitive impairments.
AB  - The Natural Language Paradigm (NLP) has proven effective in increasing
      spontaneous verbalizations for children with autism. This study investigated the
      use of NLP with older adults with cognitive impairments served at a leisure-based
      adult day program for seniors. Three individuals with limited spontaneous use of
      functional language participated in a multiple baseline design across
      participants. Data were collected on appropriate and inappropriate vocalizations
      with appropriate vocalizations coded as prompted or unprompted during baseline
      and treatment sessions. All participants experienced increases in appropriate
      speech during NLP with variable response patterns. Additionally, the two
      participants with substantial inappropriate vocalizations showed decreases in
      inappropriate speech. Implications for intervention in day programs are
      discussed.

PMID- 16889936
TI  - Arginine-enriched diet limits plasma and muscle glutamine depletion in head
      injured rats.
AB  - OBJECTIVE: Injury is associated with a depletion in glutamine (GLN) pools, which
      may contribute to impairment of immune and nutritional statuses. Total parenteral
      nutrition enriched with arginine (ARG) is able to generate GLN in surgical
      patients. We hypothesized that this same concept may be applicable to enteral
      administration and could be extended to muscle GLN reserves. This study
      investigated the ability of an enteral formula enriched with ARG to restore the
      GLN pools in an experimental model of head injury. METHODS: Twenty-five male
      Sprague-Dawley rats were randomized into 4 groups: ad libitum access to food,
      head injury plus free access to nutrition, head injury plus standard enteral
      nutrition (Sondalis), and an immune-enhancing diet (IED). The two enteral diets
      were adjusted to be isocaloric (290 kcal.kg(-1).d(-1)) and isonitrogenous (3.29
      g.kg(-1).d(-1)) and were delivered for 4 d (24 h/24 h). After sacrifice, plasma
      and muscle amino acids were determined. RESULTS: Head injury was associated with
      a large depletion of muscle and plasma GLN pools that were restored by IED
      administration but not by the standard diet. Moreover, the IED but not the
      standard diet improved or normalized ornithine and glutamate pools, suggesting
      that the modification of GLN pools is related to ARG administration. CONCLUSION:
      In our model of head injury, our IED, a diet without free GLN, is efficient in
      restoring the plasma and muscle pools of GLN, probably due to its high ARG
      content.

PMID- 16889937
TI  - Adipose tissue resistin levels in patients with anorexia nervosa.
AB  - OBJECTIVE: Resistin is a specific fat-derived hormone that affects fuel
      homeostasis and insulin action in rodents. However, its role in human physiology
      and pathophysiologic conditions, such as malnutrition, remains uncertain.
      METHODS: To enhance understanding of the role of resistin in the pathophysiology
      of anorexia nervosa (AN), we measured plasma resistin levels in 13 women with a
      restrictive type of AN and in 16 healthy age-matched women (control). Further, we
      measured resistin levels in the subcutaneous adipose tissue of eight women from
      the AN group and eight women from the control group with an in vivo microdialysis
      technique (CMA/107 pump, CMA/60 catheters, CMA Microdialysis AB, Solna, Sweden).
      RESULTS: Body mass index, percentage of body fat, fasting plasma leptin and
      insulin, and homeostasis model assessment index for insulin resistance were
      severely decreased in patients with AN compared with the control group. Plasma
      resistin levels were significantly decreased in patients with AN (P < 0.05),
      whereas subcutaneous adipose tissue resistin levels were significantly increased
      in patients with AN compared with the control group (P < 0.05). In both groups,
      plasma resistin levels showed no significant relation to resistin in dialysate,
      percentage of body fat, body mass index, homeostasis model assessment index for
      insulin resistance, and fasting plasma leptin levels. CONCLUSION: We demonstrated
      that AN is associated with decreased plasma resistin levels and increased
      resistin levels in extracellular space of the abdominal adipose tissue. Plasma
      resistin levels in patients with AN or in healthy normal-weight women were not
      directly related to body mass index, percentage of body fat, plasma leptin
      levels, and insulin sensitivity.

PMID- 16889938
TI  - A new mutation in exon 3 of the SCL39A4 gene in a Tunisian family with severe
      acrodermatitis enteropathica.
AB  - Acrodermatitis enteropathica is a rare autosomal recessive disease that manifests
      as an inability of the affected individual to absorb intestinal zinc, and
      therefore patients have nutritional zinc deficiency. Without zinc therapy, this
      condition is fatal. Mutations in the SLC39A4 gene are responsible for
      acrodermatitis enteropathica. This gene encodes one member of a human zinc/iron
      regulated transporter-like protein, also known as ZIP4, and consists of 12 exons
      and spans about 4.7 kb. We describe a novel mutation in a Tunisian family in
      which a chain termination codon in exon 3 yielded a truncated ZIP4 zinc
      transporter protein.

PMID- 16889939
TI  - Effects of transitory lingual nerve impairment on speech: an acoustic study of
      sibilant sound /s/.
AB  - By measuring spectral characteristics of the sibilant /s/ this study investigated
      whether the reduced orosensory feedback caused by lingual nerve impairment
      affects the acoustics and articulation of sibilants. A further goal was to
      examine speakers' capability to compensate for the deviant control of the
      delicate movements required for the proper production of /s/ by experimentally
      modifying the function of the tongue in a way that reduces the necessary
      somatosensory information in articulation. Five healthy men with no speech,
      language or hearing abnormalities were enrolled. They produced the sibilant /s/
      in a variety of phonetic contexts in two sessions: first in normal conditions and
      then with local anaesthesia of the right lingual nerve. From the speech samples,
      the spectral characteristics of the sibilant sound (i.e. the centre of gravity,
      standard deviation, skewness and kurtosis) were analysed acoustically. The
      results showed that the reduced tactile sensation has effects on the tongue
      function resulting in individual and variable spectral alterations. The variation
      between different speakers indicates individual ability to compensate for the
      effects caused by the sensory dysfunction of the tongue. It seems, therefore,
      that the compensatory mechanisms for speech production are highly speaker
      dependent.

PMID- 16889940
TI  - Early effect of sodium valproate and carbamazepine monotherapy on homocysteine
      metabolism in children with epilepsy.
AB  - Plasma total homocysteine (p-tHcy), serum folate (s-F), serum vitamin B-12 (s
      B12) and plasma pyridoxal-5'-phosphate (p-PLP) were measured in epileptic
      children before and after a 20-week period of sodium valproate (group A, n=32)
      and carbamazepine (group B, n=20) monotherapy. P-tHcy significantly increased in
      both groups, s-F and s-B12 significantly increased in group A, while s-F and p
      PLP significantly decreased in group B. Our study showed an early effect of
      antiepileptic drug treatment on homocysteine metabolism.

PMID- 16889941
TI  - Felbamate: consensus of current clinical experience.
AB  - An expert panel convened to evaluate data and review current clinical practices
      regarding the novel antiepileptic drug (AED) felbamate. Felbamate has
      demonstrated efficacy against a variety of refractory seizures types, including
      seizures associated with Lennox-Gastaut syndrome, but postmarketing experience
      revealed serious idiosyncratic adverse effects that were not observed during
      clinical trials. Although felbamate is not indicated as first-line antiepileptic
      therapy, its utility in treating seizures that are refractory to other AEDs is
      undisputed, as shown by the number of patients who continue to use it. New
      exposures to felbamate number approximately 3200-4200 patients annually, and it
      is estimated that over the past 10 years, approximately 35,000 new starts have
      occurred. Recommendations by the American Academy of Neurology and a review of
      felbamate literature were evaluated in conjunction with the clinical experience
      of the expert panel to determine current medical opinion and practice regarding
      felbamate. The past 10 years of clinical experience have demonstrated that when
      used in accordance with existing recommendations and close clinical monitoring,
      felbamate is an effective treatment for some patients with seizures refractory to
      other AEDs. This review of clinical data and discussion of the current
      understanding of the risk:benefit of felbamate therapy supports its use as an
      important therapeutic option for some patients with refractory epilepsy.

PMID- 16889942
TI  - Neonatal seizure classification: a fetal perspective concerning childhood
      epilepsy.
AB  - Neonatal seizures are markers for time-specific etiologies during antepartum,
      intrapartum and neonatal time periods. Seizures with or without encephalopathic
      signs can represent a continuum of maternal, placental, fetal and neonatal risk
      factors and disease states. A multi-dimensional classification scheme for
      neonatal seizures is suggested that will help strategize specific therapeutic
      interventions to optimize neurologic outcome and anticipate later neurological
      morbidities including epilepsy risk. This scheme combines "epileptic" and "non
      epileptic" seizure descriptions which capture time-specific and brain region
      specific mechanisms for seizures. Synchronized video electroencephalographic
      monitoring provides the most accurate start and endpoints for cortically
      generated seizures. However, subcortical sites of injury may also initiate
      abnormal clinical signs with or without the subsequent expression of
      electrographic seizures. Co-registration of digital neuroimaging techniques such
      as magnetic resonance imaging with computational electroencephalographic datasets
      will provide more precise structure-function correlates for neonatal seizures
      that address both cortical and subcortical sites of injury. Finally, more precise
      definitions of neonatal status epilepticus need to be established because of the
      long-term harmful effects on brain development by prolonged seizures expressed as
      epilepsy and cognitive-behavioral deficits. With this expanded classification
      scheme for neonatal seizures, novel pharmacologic and surgical strategies can be
      designed for disease-specific rescue, repair, and regeneration strategies of
      damaged brain tissue that occur during fetal and neonatal periods, and are later
      expressed during infancy and childhood. Clinical neuroscientists must strive to
      develop a classification scheme that bridges bench to bedside concepts of
      developmental neural plasticity research, recognizing both negative and positive
      consequences of brain remodeling and repair of the child and adolescent brain.
      Developmental neural plasticity also extends into adulthood when brain remodeling
      mechanisms further contribute to epileptogenesis and continues to impair quality
      of life.

PMID- 16889943
TI  - Alterations of TGF-beta/Smad mRNA expression in atopic dermatitis following
      narrow-band ultraviolet B phototherapy: results of a pilot study.

PMID- 16889944
TI  - Juvenile stress induces a predisposition to either anxiety or depressive-like
      symptoms following stress in adulthood.
AB  - Epidemiological studies indicate that childhood trauma is predominantly
      associated with later emergence of several stress-related psychopathologies.
      While most 'early-stress' animal models focus on pre-weaning exposure, we
      examined the consequences of exposure to stress during the early pre-pubertal
      period, "juvenile stress", on adulthood stress responses. Following two different
      juvenile stress protocols, predator scent or short-term variable stress, we
      examined adulthood stress responses using the elevated plus-maze and startle
      response or exploration and avoidance learning. Employing Cut-off Behavioral
      Criteria analyses of clustering symptoms on the rats' altered stress responses
      discriminated between different patterns of maladaptive behaviors. Exposure to
      either juvenile stress protocols resulted in lasting alteration of stress
      responses with the majority of rats exhibiting anxiety-like behaviors, while the
      remaining third displayed depressive-like behaviors. The results suggest that the
      presented "Juvenile stress" model may be relevant to the reported predisposition
      to develop both anxiety and depression following childhood trauma.

PMID- 16889945
TI  - Decoupling residual dipolar coupling between 13C and14N spin pairs in CPMAS NMR.
AB  - Decoupling of the residual dipolar coupling between (13)C and(14)N nuclei is
      investigated experimentally in a triple resonance experiment. It is shown that
      pulsed decoupling can be used to give enhanced sensitivity and reduced line
      widths and the technique is illustrated using short peptides.

PMID- 16889946
TI  - Intelligent medical training systems.

PMID- 16889947
TI  - 15-Hydroperoxyeicosapentaenoic acid, but not eicosapentaenoic acid, shifts
      arachidonic acid away from cyclooxygenase pathway into acyl-CoA synthetase
      pathway in rabbit kidney medulla microsomes.
AB  - Under physiological conditions, small amounts of free arachidonic acid (AA) are
      released from membrane phospholipids, and cyclooxygenase (COX) and acyl-CoA
      synthetase (ACS) competitively act on this fatty acid to form prostaglandins
      (PGs) and arachidonoyl-CoA (AA-CoA). In the present study, we investigated the
      effects of eicosapentaenoic acid (EPA) and 15-hydroperoxyeicosapentaenoic acid
      (15-HPEPE) on the PG and AA-CoA formations from high and low concentrations of AA
      (60 and 5 microM) in rabbit kidney medulla microsomes. The kidney medulla
      microsomes were incubated with 60 or 5 microM [(14)C]-AA in 0.1M Tris/HCl buffer
      (pH 8.0) containing cofactors of COX (reduced glutathione and hydroquinone) and
      cofactors of ACS (ATP, MgCl(2) and CoA). After incubation, PG (as total PGs), AA
      CoA and residual AA were separated by selective extraction using petroleum ether
      and ethyl acetate. EPA reduced the PG and AA-CoA formations from both 60 and 5
      microM AA. In contrast, 15-HPEPE decreased the PG formation without affecting the
      AA-CoA formation from 60 microM AA, and increased the AA-CoA formation at the
      expense of PG formation when 5 microM AA was used as substrate concentration. The
      experiments utilizing Fe(2+) and an electron spin resonance (ESR) revealed that
      15-HPEPE elicits these effects in the form of hydroperoxy adduct. These results
      suggest that 15-HPEPE, but not EPA, has the potential to shift AA away from COX
      pathway into ACS pathway at low substrate concentration (close to the
      physiological concentration of AA).

PMID- 16889948
TI  - ENU-mutagenesis: insight into immune function and pathology.
AB  - In random chemical mutagenesis, gene discovery is driven by phenotypes rather
      than by hypotheses. A standard dose of N-ethyl-N-nitrosourea results in
      approximately 30 coding mutations in male G1 mice, of which approximately 4 can
      be propagated to homozygosity in 3 generations. In recent years, large-scale
      screens of such G3 mice for phenotypes of interest to immunologists have revealed
      clues to the number of genes responsible for key immune responses, such as innate
      recognition of pathogens and autoantibody production. More than 20 of the
      phenotypes that exhibit a simple (Mendelian) pattern of inheritance have been
      mapped. Novel alleles have revealed new pathways of host defense, allergy and
      autoimmunity.

PMID- 16889949
TI  - The cost of treating patients with COPD in Denmark--a population study of COPD
      patients compared with non-COPD controls.
AB  - This paper describes a population-based study of health care resource use of
      patients with chronic obstructive pulmonary disease (COPD) compared to non-COPD
      controls. Through a screening of the Danish Patient Registry for patients
      admitted with COPD diagnoses for a 5-year period, 1998-2002, 66,000 individuals
      with COPD still alive at the beginning of 2002 were identified. Their use of
      health care resources in 2002 were compared with equivalent data, stratified for
      age, sex and mortality rates, for a control population without COPD based on data
      for the 300,000 remaining patients on the Danish Patient Registry in 2002.
      Results indicated that the gross cost of treating patients with COPD in the
      Danish somatic hospital and primary health care sector corresponded to 10% of the
      total cost of treating patients of 40 years or more. The net cost for COPD
      patients was 1.9 billion DKK (256 million euro), 6% of the total annual costs of
      treating the population of 40 years or more. The gross cost related to any
      disease and the net cost reflected the resource use which could be attributed to
      COPD and its related diagnoses. The incidence of inpatient hospital admissions
      was almost four times higher in the COPD population than in the control group.
      COPD patients contacted their general practitioner 12 times more per year than
      non-COPD controls, but for specialist and paramedic treatment in the primary care
      sector there was no significant difference between COPD patients and non-COPD
      controls. Only one third of the COPD costs were due to treatment of COPD as the
      primary diagnosis. The remaining two-thirds of the COPD-related costs were mainly
      due to admissions for other diseases such as cardio-vascular diseases, other
      respiratory diseases, and cancer.

PMID- 16889950
TI  - Tumor necrosis factor receptors (TNFRs) on T lymphocytes and soluble TNFRs in
      different clinical courses of sarcoidosis.
AB  - INTRODUCTION: The release of tumor necrosis factor (TNF-alpha) is increased in
      sarcoidosis patients. TNF-alpha exerts its effect by binding to specific cell
      surface receptors. There are only fragmentary data concerning the expression of
      tumor necrosis factor receptors (TNFRs) on bronchoalveolar lavage fluid (BALF)
      and peripheral blood (PB) lymphocytes. The aim of the study was to evaluate TNFRI
      (CD120a) and TNFRII (CD120b) expression on T cells and the level of soluble TNFRs
      in specimens of patients with different clinical manifestation and clinical
      outcome of sarcoidosis. MATERIAL AND METHODS: We examined 49 patients with newly
      diagnosed pulmonary sarcoidosis. TNFRI and TNFRII density on CD4+ and CD8+ BALF
      and PB cells surface was estimated using monoclonal antibodies and a flow
      cytometry technique. The level of TNFRs in PB serum and BALF cell culture
      supernatant (CCS) was measured using ELISA. Immunological analyses were also
      performed on PB samples collected from 10 healthy volunteers. RESULTS: The level
      of soluble TNFRI (sTNFRI) in PB serum was similar in sarcoidosis patients and
      healthy subjects, whereas the concentration of sTNFRII in serum was significantly
      higher in the sarcoidosis group (P<0.001). Patients without acute symptoms of
      sarcoidosis, patients with radiological stage II/III as well as patients with
      further disease progression showed a tendency to higher levels of sTNFRs in PB
      serum and lower levels of sTNFRs in BALF CCS compared to Lofgren syndrome and
      radiological stage I subjects, and patients with spontaneous resolution of
      sarcoidosis. More than 80% of BALF and PB lymphocytes of sarcoidosis patients
      expressed both CD120a and CD120b antigens. The percentage of double-positive
      CD4+CD120a+ and CD4+CD120b+ cells in PB was significantly higher (P<0.005) in
      sarcoidosis patients than in healthy subjects. The highest percentage of
      CD4+CD120a+ and CD4+CD120b+ lymphocytes in BALF was determined in patients with
      acute disease, and in PB of patients with further spontaneous improvement.
      CONCLUSION: The evaluation of sTNFRs and TNFRs expression on T-helper cells may
      be useful in the estimation of sarcoidosis activity.

PMID- 16889951
TI  - Optimum expression of adult lung function based on all-cause mortality: results
      from the Reykjavik study.
AB  - A variety of reference curves are used to derive predicted values for adult lung
      function, even within ethnically similar populations. Alternatives to percentage
      predicted value are sometimes used to allow for height in research. Strength of
      association with total mortality can be used to choose the optimal expression,
      between forced expiratory volume in 1s (FEV(1)) divided by height(2),
      FEV(1)/height(3), FEV(1)% predicted and difference from predicted. Data from the
      Reykjavik Study cohort, 1976-2002, included 5544 men and 8062 women randomly
      selected from the population. Total mortality was analysed by Cox proportional
      hazards regression in relation to each height-adjusted measure, allowing for age
      group, period of recruitment and body mass index, and smoking before or at
      baseline. FEV(1)/height(2) and FEV(1)/height(3) had stronger associations with
      mortality than FEV(1)% predicted and difference from predicted in men and in
      women. There were similar findings for forced vital capacity (FVC) in non-smokers
      and in women. FEV(1)/height(2) was slightly better predictive than
      FEV(1)/height(3) in men, but distributions of FEV(1)/height(3) in men and women
      were closer than those of FEV(1)/height(2). Clinical practise and epidemiological
      research would benefit from agreement on how to adjust lung function for height.
      Replication of these analyses in other cohort studies would inform the choice
      between FEV(1)/height(2) and FEV(1)/height(3).

PMID- 16889952
TI  - Potency ratio fluticasone propionate (Flixotide Diskus)/budesonide (Pulmicort
      Turbuhaler).
AB  - In the choice of, or switch between, various inhaled corticosteroids (ICS) it is
      important to know equipotent doses for clinical treatment effects of the
      alternatives. Various ICS do have different inherent potency. Further, the ICS
      are delivered from inhalers that may differ markedly in output characteristics
      and drug delivery to intrapulmonary airways. Therefore, clinical efficacy
      comparisons must include drug-inhaler comparisons. We estimated the therapeutic
      potency ratio of the Flixotide Diskus (fluticasone propionate, FP) and the
      Pulmicort Turbuhaler (budesonide, BUD) in steroid-naive asthma patients, using a
      dose-reduction technique (FP 500-0 mcg/day, BUD 800-0 mcg/day). The dose defining
      end point was loss of asthma control in this paper denoted as exacerbation. In
      total, 282 patients with proven asthma were enrolled in the study, and 103 in the
      FP group and 98 in the BUD group completed the study per protocol. In total, 80
      patients in the FP-group and 79 in the BUD-group experienced a dose defining
      exacerbation. The exacerbation frequency increased in a dose-dependent way as the
      dose was titrated down. From these data the potency difference between the
      present drug inhaler combinations, Flixotide Diskus and Pulmicort Turbuhaler, was
      calculated to be between 1.50:1 (95% CI 1.10:1-2.05:1) and 1.75:1 (CI 1.26:1
      2.43:1) depending on if patients with insufficient steroid-response were excluded
      from the calculations or not. In these steroid-naive patients, the potency
      difference was evident only at low daily doses, below 200 mcg.

PMID- 16889953
TI  - Estimation of solid phase affinity constants using resistive-pulses from
      functionalized nanoparticles.
AB  - This paper describes a method for estimating the solid phase affinity constant of
      antibodies by using resistive-pulse (Coulter counting) data from spherical
      nanoparticles that expose antigens. We developed this technique by analyzing data
      published recently by Saleh, O.A., Sohn, L.L., 2003a. Proc. Natl. Acad. Sci.
      U.S.A. 100, 820-824. These authors used resistive-pulse sensing to detect an
      increase in the diameter of streptavidin-functionalized colloids due to the
      binding of monoclonal anti-streptavidin antibodies. Based on further analysis of
      their data, we were able to determine the number of antibodies bound to the
      colloids at various antibody concentrations. This information made it possible to
      estimate the solid phase affinity constant of the interaction by fitting the data
      with binding isotherms that describe the binding equilibrium between antibody and
      antigen. We calculated a value of 2.6x10(8)+/-0.8x10(8) M-1 which is in agreement
      with the specifications of the supplier of the antibody.

PMID- 16889954
TI  - Fibre-optic bacterial biosensors and their application for the analysis of
      bioavailable Hg and As in soils and sediments from Aznalcollar mining area in
      Spain.
AB  - Fibre-optic biosensors for Hg and As were developed by attaching alginate
      immobilised recombinant luminescent Hg- and As-sensor bacteria onto optical
      fibres. The optimised biosensors (consisting of seven layers of fibre-attached
      bacteria pre-grown till mid-logarithmic growth phase) enabled quantification of
      environmentally relevant concentrations of the target analytes: 2.6 microg l-1 of
      Hg(II) and 141 microg l-1 of As(V) or 18 microg l-1 of As(III). The highest
      viability and sensitivity for target analyte was obtained when fibre tips were
      stored in CaCl2 solution at -80 degrees C. Applicability of the fibre-optic
      biosensors in parallel to the respective non-immobilised sensors was assessed on
      10 natural soil and sediment samples from Aznalcollar mining area (Spain). On the
      average 0.2% of the total Hg and 0.87% of the total As proved bioavailable to
      fibre-attached bacteria. Interestingly, about 20-fold more Hg and 4-fold more As
      was available to non-immobilised sensor bacteria indicating the importance of
      direct cell contact (possible only for non-immobilised cells) for enhanced
      bioavailability of these metals in solid samples.

PMID- 16889955
TI  - Location, allocation, relocation: isolating adult tissue stem cells in three
      dimensions.
AB  - The literature on isolation of adult tissue stem cells is vast and disparate. To
      better organize the field, we redefine 'isolation', re-expressing it as the sum
      of three component vectors: location, allocation and relocation. Location is the
      isolation of stem cells in situ by anatomical features. Allocation is physical
      isolation by cell sorting. Relocation is isolation of the functional properties
      of a stem cell to regenerate its normal progeny when relocated to a new
      environment. Techniques for the allocation and relocation of stem cells from
      certain tissues (e.g. hematopoietic) are currently better defined than their
      location, whereas those of other tissues (e.g. mammary glands) have had recent
      advances along all three vectors. Yet another group (e.g. gastric glands), have
      stem cells with well characterized location, emerging techniques for allocation
      but still rudimentary techniques for relocation.

PMID- 16889956
TI  - Engineered systems for the physical manipulation of single cells.
AB  - Manipulating the physical location of cells is useful both to organize cells in
      vitro and to separate cells during screening. The quest to manipulate cells on
      length scales commensurate with their size has led to a host of technologies
      exploiting optical, chemical, mechanical, electrical, and other phenomena.
      Researchers interested in organizing cells are gaining the ability to pattern
      more than two cell types, to create dynamic surfaces, and to pattern cells in the
      third dimension. In the realm of cell separation for screening, there has been
      significant progress in miniaturized flow-based optical sorters as well as in
      sorting following static microscopic observation.

PMID- 16889957
TI  - Calcitriol sensitizes colon cancer cells to H2O2-induced cytotoxicity while
      inhibiting caspase activation.
AB  - The anti-cancer activity of calcitriol, the active metabolite of Vitamin D, in
      the colon is usually attributed to its anti-proliferative and pro-differentiative
      actions. The levels of reactive oxygen species (ROS) are high in colon carcinomas
      due to increased aerobic metabolism and exposure to various anti-cancer
      modalities. We examined whether calcitriol modulates the response of colon cancer
      cells to the cytotoxic action of the common mediator of ROS injury, H2O2.
      Pretreatment with calcitriol (100 nM, 48 h) sensitized HT-29 colon cancer cells
      to cell death induced by acute exposure to H2O2 or chronic exposure to the H2O2
      generating system, glucose/glucose-oxidase. Although the morphological features
      of H2O2-induced HT-29 cell death are consistent with apoptosis, we detected no
      executioner caspase activation in response to cytotoxic concentrations of H2O2
      and treatment with a pan-caspase inhibitor did not affect H2O2-induced
      cytotoxicity nor its enhancement by calcitriol. Conversely, exposure of HT-29
      cells to sub-toxic concentrations of H2O2 resulted in low executioner caspase
      activation that was inhibited by pretreatment with calcitriol. The sensitization
      of colon cancer cells to ROS-induced cytotoxicity may contribute to its assumed
      action as a chemopreventive agent and to its therapeutic potential alone or in
      combination with other anti-cancer modalities.

PMID- 16889959
TI  - Benzodiazepine calcitonin gene-related peptide (CGRP) receptor antagonists:
      optimization of the 4-substituted piperidine.
AB  - In our continuing effort to identify CGRP receptor antagonists for the acute
      treatment of migraine, we have undertaken a study to evaluate alternative 4
      substituted piperidines to the lead dihydroquinazolinone 1. In this regard, we
      have identified the piperidinyl-azabenzimidazolone and phenylimidazolinone
      structures which, when incorporated into the benzodiazepine core, afford potent
      CGRP receptor antagonists (e.g., 18 and 29). These studies produced a potent
      analog (18) which overcomes the instability issues associated with the lead
      structure 1. A general pharmacophore for the 4-substituted piperidine component
      of these CGRP receptor antagonists is also presented.

PMID- 16889960
TI  - 1-Alkyl-2-aryl-4-(1-naphthoyl)pyrroles: new high affinity ligands for the
      cannabinoid CB1 and CB2 receptors.
AB  - Two series of 1-alkyl-2-aryl-4-(1-naphthoyl)pyrroles were synthesized and their
      affinities for the cannabinoid CB(1) and CB(2) receptors were determined. In the
      2-phenyl series (5) the N-alkyl group was varied from n-propyl to n-heptyl. A
      second series of 23 1-pentyl-2-aryl-4-(1-naphthoyl)-pyrroles (6) was also
      prepared. Several compounds in both series have CB(1) receptor affinities in the
      6-30nM range. The high affinities of these pyrrole derivatives relative to JWH
      030 (1, R=C(5)H(11)) support the hypothesis that these pyrroles interact with the
      CB(1) receptor primarily by aromatic stacking.

PMID- 16889958
TI  - Rational proteomics V: structure-based mutagenesis has revealed key residues
      responsible for substrate recognition and catalysis by the dehydrogenase and
      isomerase activities in human 3beta-hydroxysteroid dehydrogenase/isomerase type
      1.
AB  - Mammalian 3beta-hydroxysteroid dehydrogenase/isomerase (3beta-HSD) is a member of
      the short chain dehydrogenase/reductase. It is a key steroidogenic enzyme that
      catalyzes the first step of the multienzyme pathway conversion of circulating
      dehydroepiandrosterone and pregnenolone to active steroid hormones. A three
      dimensional model of a ternary complex of human 3beta-HSD type 1 (3beta-HSD_1)
      with an NAD cofactor and androstenedione product has been developed based upon X
      ray structures of the ternary complex of E. coli UDP-galactose 4-epimerase
      (UDPGE) with an NAD cofactor and substrate (PDB_AC: 1NAH) and the ternary complex
      of human type 1 17beta-hydroxysteroid dehydrogenase (17beta-HSD_1) with an NADP
      cofactor and androstenedione (PDB_AC: 1QYX). The dimeric structure of the enzyme
      was built from two monomer models of 3beta-HSD_1 by respective 3D superposition
      with A and B subunits of the dimeric structure of Streptococcus suis DTDP-D
      glucose 4,6-dehydratase (PDB_AC: 1KEP). The 3D model structure of 3beta-HSD_1 has
      been successfully used for the rational design of mutagenic experiments to
      further elucidate the key substrate binding residues in the active site as well
      as the basis for dual function of the 3beta-HSD_1 enzyme. The structure based
      mutant enzymes, Asn100Ser, Asn100Ala, Glu126Leu, His232Ala, Ser322Ala and
      Asn323Leu, have been constructed and functionally characterized. The mutagenic
      experiments have confirmed the predicted roles of the His232 and Asn323 residues
      in recognition of the 17-keto group of the substrate and identified Asn100 and
      Glu126 residues as key residues that participate for the dehydrogenase and
      isomerization reactions, respectively.

PMID- 16889961
TI  - Novel aminobenzimidazoles as selective MCH-R1 antagonists for the treatment of
      metabolic diseases.
AB  - A series of novel aminobenzimidazoles was prepared and evaluated for h-MCH-R1
      antagonist properties. Most of the compounds showed excellent h-MCH-R1 binding
      affinity as well as mouse ex vivo binding. Compounds 9 and 18 were active in
      mouse DIO studies at 30mpk.

PMID- 16889962
TI  - Antiprotozoal activities of new bis-chlorophenyl derivatives of bicyclic octanes
      and aza-nonanes.
AB  - The in vitro activity of newly synthesized bis-(chlorophenyl)
      azabicyclo[3.2.2]nonanes and bis-(chlorophenyl)-bicyclo[2.2.2]octanes against
      Plasmodium falciparum K(1) (resistant to chloroquine and pyrimethamine) and
      Trypanosoma brucei rhodesiense was investigated. Especially the bis
      (chlorophenyl)-azabicyclo[3.2.2]nonanes exhibit promising antitrypanosomal
      activity and were tested in vivo against Trypanosoma brucei brucei featuring
      moderate activities.

PMID- 16889963
TI  - The molecular basis for the selection of captopril cis and trans conformations by
      angiotensin I converting enzyme.
AB  - Enzyme-inhibitor recognition is considered one of the most fundamental aspects in
      the area of drug discovery. However, the molecular mechanism of this recognition
      process (induced fit or prebinding and adaptive selection among multiple
      conformers) in several cases remains unexplored. In order to shed light toward
      this step of the recognition process in the case of human angiotensin I
      converting enzyme (hACE) and its inhibitor captopril, we have established a novel
      combinatorial approach exploiting solution NMR, flexible docking calculations,
      mutagenesis, and enzymatic studies. We provide evidence that an equimolar ratio
      of the cis and trans states of captopril exists in solution and that the enzyme
      selects only the trans state of the inhibitor that presents architectural and
      stereoelectronic complementarity with its substrate binding groove.

PMID- 16889965
TI  - Synthesis, X-ray crystal structural study, antiviral and cytostatic evaluations
      of the novel unsaturated acyclic and epoxide nucleoside analogues.
AB  - A series of the novel purine and pyrimidine nucleoside analogues were synthesised
      in which the sugar moiety was replaced by the 4-amino-2-butenyl (2-6 and 10-18)
      and oxiranyl (8 and 20) spacer. The Z- (2-6) and E-isomers (10-18) of unsaturated
      acyclic nucleoside analogues were synthesized by condensation of 2- and 6
      substituted purine and 5-substituted uracil bases with Z- (1) or E-phthalimide
      (9) precursors. The oxiranyl nucleoside analogues (8 and 20) were obtained by
      epoxidation of 1 and 9 with m-chloroperoxybenzoic acid and subsequent coupling
      with adenine. The new compounds were evaluated for their antiviral and antitumor
      cell activities. Among the olefinic nucleoside analogues, Z-isomer of adenine
      containing 4-amino-2-butenyl side chain (6) exhibited the best cytostatic
      activities, particularly against colon carcinoma (SW 620, IC50 = 26 microM). Its
      E-isomer 15 did not show any antiproliferative activity against malignant tumor
      cell lines, except for a slight inhibition of colon carcinoma (SW 620, IC50 =
      56.5 microM) cells. In general, Z-isomers showed better cytostatic activities
      than the corresponding E-isomers. (Z)-4-Amino-2-butenyl-adenine nucleoside
      analogue 6 showed albeit modest but selective activity against HIV-1 (EC50 = 4.83
      microg mL(-1)).

PMID- 16889964
TI  - Synthesis and biological activities of 7-aza rebeccamycin analogues bearing the
      sugar moiety on the nitrogen of the pyridine ring.
AB  - The synthesis of a new family of 7-aza-rebeccamycin analogues in which the sugar
      moiety is attached to the nitrogen of the pyridine ring is described. The
      capacity of the newly synthesized compounds to bind to DNA and to inhibit
      topoisomerase I has been evaluated. Their cytotoxicities toward four tumor cell
      lines, one murine leukemia L1210 and three human tumor cell lines, one prostate
      carcinoma DU145, one colon carcinoma HT29, and one non-small cell lung carcinoma
      A549, have been determined. Their abilities to inhibit the checkpoint kinase Chk1
      have been evaluated.

PMID- 16889966
TI  - Dicationic DNA-targeted antiprotozoal agents: naphthalene replacement of
      benzimidazole.
AB  - A series of naphthalene analogues of highly active benzimidazole diamidines were
      synthesized using sequential Stille and Suzuki coupling reactions for preparation
      of the bis-nitrile intermediates. All of the diamidines showed strong DNA
      affinities as judged by high DeltaTm values with poly(dA-dT). The dicationic
      compounds were quite active in vitro versus Trypanosoma brucei rhodesiense (T. b.
      r.) exhibiting IC50 values ranging from 4 to 98 nM. These compounds were also
      active versus Plasmodium falciparum (P. f.) giving IC50 values ranging from 4 to
      33 nM. Two of the compounds showed good activity in vivo in the STIB900 model for
      acute African trypanosomiasis; one gave 3/4 cures and the other gave 4/4 cures on
      ip dosage of 20 mg/kg for 4 days. The amidoxime prodrugs of the naphthalene
      analogues were essentially ineffective.

PMID- 16889967
TI  - Design and synthesis of novel imidazoline derivatives with potent
      antihyperglycemic activity in a rat model of type 2 diabetes.
AB  - Imidazoline derivatives have been reported to show antihyperglycemic activity in
      vivo. In the present study, we first showed that there was no correlation between
      the in vivo antidiabetic activity and the in vitro affinities for the I1/I2
      binding sites for several substituted aryl imidazolines. Among these compounds, 2
      (alpha-cyclohexyl-benzyl)-4,5-dihydro-1H-imidazole 2 exhibited potent
      antihyperglycemic properties. It was then chosen as lead compound. Thirty-six new
      derivatives were synthesized by replacing the cyclohexyl/benzyl group by various
      cyclic systems or the imidazoline ring by isosteric heterocycles. These compounds
      were evaluated in vivo for their antihyperglycemic activity using an oral glucose
      tolerance test (OGTT) in a rat model of type-2 diabetes obtained by giving a
      single intravenous (iv) injection of a low dose of streptozotocin to rats (STZ
      rats) and in normal rats. Nine compounds with an imidazoline moiety, possibly
      substituted by a methyl group, had a potent effect on the glucose tolerance in
      normal or STZ-diabetic rats, after an oral (po) administration of the test
      compound at a dose of 30 or 10 mg kg(-1), without any hypoglycemia. Replacement
      of the imidazoline ring by isosteric heterocycles resulted in a total loss of
      activity.

PMID- 16889969
TI  - Electron microscopy characterization of nanostructured carbon obtained from
      chlorination of metallocenes and metal carbides.
AB  - In this work we report some new well-defined carbon nanostructures produced by
      direct chlorination of metallocenes (ferrocene and cobaltocene) and NbC, at
      temperatures from 100 to 900 degrees C. Thus, amorphous carbon nanotubes with
      variable dimensions depending on reaction temperature were produced from
      ferrocene. When cobaltocene is the carbon precursor the main product are solid
      amorphous nanospheres. The high refractory metal carbide NbC as carbon source
      favours the growth of nanospherical cabbage-like particles with a higher degree
      of graphene sheets order. Besides, NbC crystallites encapsulated in an amorphous
      carbon shell were also found at lower temperatures (T< or =700 degrees C).

PMID- 16889968
TI  - Identification and evaluation of antioxidant, analgesic/anti-inflammatory
      activity of the most active ninhydrin-phenol adducts synthesized.
AB  - Treatment of phenols with ninhydrin in acidic medium afforded 2-hydroxy-2-(ortho
      hydroxy-phenyl/naphthyl)-1,3-dioxoindanes, which being unstable were isolated in
      their hemiketal forms. These synthesized compounds were subjected to TLC
      screening for radical scavenging and in vitro lipoxgenase and cycloxygenase
      enzyme inhibition assays. The best compound was identified and studied in detail
      for steady-state and time-resolved free radical kinetics, viz., DPPH, ABTS(-),
      *OH and rate constants for these reactions were evaluated. The best compound was
      also subjected to in vivo anti-inflammatory and analgesic activities in which the
      compound showed good promise for further structural optimization.

PMID- 16889970
TI  - Lipopolysaccharide-responsive phosphoproteins in Nicotiana tabacum cells.
AB  - Mounting evidence is merging to affirm the effectiveness of bacterial
      lipopolysaccharides (LPS) as biological control agents, inducers of innate
      immunity, and to stimulate/potentiate the development of defense responses in
      plants through protein phosphorylation-mediated signal perception/transduction
      responses. In vivo labeling of protein phosphorylation events during signal
      transduction indicated the rapid phosphorylation of several proteins. Substantial
      differences and de novo LPS-induced phosphorylation were also observed with two
      dimensional analysis. In this study, qualitative and quantitative changes in
      phosphoproteins of Nicotiana tabacum suspension cells during elicitation by LPS
      from the Gram-negative bacteria, Burkholderia cepacia, were analyzed using two
      dimensional electrophoresis in combination with a phosphoprotein-specific gel
      stain. Trypsin digested phosphoproteins were analyzed by matrix-assisted laser
      desorption ionization time-of-flight mass spectrometry (MALDI-TOF/MS) and nano
      electrospray-ionization liquid chromatography tandem mass spectrometry (nano-ESI
      LC/MS/MS). A total of 27 phosphoproteins were identified from 23 excised gel
      spots. The identified phosphoproteins indicate that LPS(B.cep)-induced signal
      perception/transduction involves G-protein coupled receptor signaling,
      Ca(2+)/calmodulin-dependent signaling pathways, H(+)-ATPase regulation of
      intracellular pH, thioredoxin-mediated signaling and phosphorylation of 14-3-3
      regulatory proteins. Other targets of LPS(B.cep)-responsive phosphorylation
      included NTP pool maintenance, heat shock proteins, protein biosynthesis and
      chaperones as well as cytoskeletal tubulin. The results add novel insights into
      the biochemical process of LPS perception and resulting signal transduction.

PMID- 16889971
TI  - Salinity-induced tissue-specific diurnal changes in nitrogen assimilatory enzymes
      in tomato seedlings grown under high or low nitrate medium.
AB  - We studied the salt stress (100 mM NaCl) effects on the diurnal changes in N
      metabolism enzymes in tomato seedlings (Lycopersicon esculentum Mill. cv. Chibli
      F1) that were grown under high nitrogen (HN, 5 mM NO(3)(-)) or low nitrogen (LN,
      0.1 mM NO(3)(-)). NaCl stress led to a decrease in plant DW production and leaf
      surface to higher extent in HN than in LN plants. Total leaf chlorophyll (Chl)
      content was decreased by salinity in HN plants, but unchanged in LN plants.
      Soluble protein content was decreased by salt in the leaves from HN and LN
      plants, but increased in the stems-petioles from LN plants. Nitrate reductase
      (NR, EC 1.6.1.6) showed an activity peak during first part of the light period,
      but no diurnal changes were observed for the nitrite reductase (NiR, EC 1.7.7.1)
      activity. Glutamine synthetase (GS, EC 6.3.1.2) and glutamate synthase (Fd-GOGAT,
      EC 1.4.7.1) activities increased in HN plant leaves during the second part of the
      light period, probably when enough ammonium is produced by nitrate reduction. NR
      and NiR activities in the leaves were more decreased by NaCl in LN than in HN
      plants, whereas the opposite response was obtained for the GS activity. Fd-GOGAT
      activity was inhibited by NaCl in HN plant leaves, while salinity did not shift
      the peak of the NR and Fd-GOGAT activities during a diurnal cycle. The induction
      by NaCl stress occurred for the NR and GS activities in the roots of both HN and
      LN plants. Glutamate dehydrogenase (GDH, EC 1.4.1.2) activity shifted from the
      deaminating activity to the aminating activity in all tissues of HN plants. In LN
      plants, both aminating and deaminating activities were increased by salinity in
      the leaves and roots. The differences in the sensitivity to NaCl between HN and
      LN plants are discussed in relation to the N metabolism status brought on by salt
      stress.

PMID- 16889972
TI  - Expression of expansin genes in strawberry varieties with contrasting fruit
      firmness.
AB  - Fruit softening is associated with cell wall disassembly mediated by the action
      of a complex set of enzymes and proteins. Expansins, a group of proteins with
      unknown enzymatic activity, are proposed to be involved in this process. In order
      to study the involvement of expansins in strawberry fruit softening we have
      analyzed the expression level of five expansin mRNAs (FaEXP1, FaEXP2, FaEXP4,
      FaEXP5 and FaEXP6) in the cultivars "Selva", "Camarosa" and "Toyonaka", which
      differ in fruit firmness during ripening. We have found a correlation between
      mRNA expression levels and fruit firmness for FaEXP1, FaEXP2 and FaEXP5. For
      these three mRNAs we have observed higher expression levels in the softest
      cultivar (Toyonaka) than in the other two firmer cultivars (Selva and Camarosa)
      at the beginning of ripening. This correlation was not found in the case of
      FaEXP4 and FaEXP6, although both genes displayed a different expression pattern
      in the three cultivars analyzed. Western-blot analysis revealed that the
      accumulation of expansin proteins begins earlier in the softest cultivar during
      ripening.

PMID- 16889974
TI  - rHsp90 gene expression in response to several environmental stresses in rice
      (Oryza sativa L.).
AB  - In this study, the gene for a rice (Oryza sativa L.) 90 kDa heat shock protein
      (rHsp90, GenBank accession no. AB037681) was identified by screening rice root
      cDNAs that were up-regulated under carbonate (NaHCO(3)) stress using the method
      of differential display, and cloned. The open-reading-frame of rHsp90-cDNA was
      predicted to encode a protein containing 810 amino acids, which showed high
      similarity to proteins in Hordeum vulgare (accession no. X67960) and Catharathus
      roseus (accession no. L14594). Further studies showed that rHsp90 mRNA
      accumulated following exposure to several abiotic stresses, including salts
      (NaCl, NaHCO(3) and Na(2)CO(3)), desiccation (using polyethylene glycol), high pH
      (8.0 and 11.0) and high temperature (42 and 50 degrees C). Yeast (Saccharomyces
      cerevisiae) over-expressing rHsp90 exhibited greater tolerance to NaCl,
      Na(2)CO(3) and NaHCO(3) and tobacco seedlings over-expressing rHsp90 could
      tolerate salt concentrations as high as 200 mM NaCl, whereas untransformed
      control seedlings couldn't. These results suggest that rHsp90 plays an important
      role in multiple environmental stresses.

PMID- 16889973
TI  - Arabidopsis thaliana fatty acid alpha-dioxygenase-1: evaluation of substrates,
      inhibitors and amino-terminal function.
AB  - Plant alpha dioxygenases (PADOX) convert fatty acids to 2-hydroperoxy products
      that are important in plant signaling pathways. The PADOX amino-terminal domain
      is distinct from that in other myeloperoxidase-family hemoproteins, and the
      positional specificity and prosthetic group of PADOX distinguish them from the
      non-heme iron plant lipoxygenases. The constraints of the PADOX active site on
      potential substrates are poorly understood and only limited structure-function
      and mechanistic information is available for these enzymes. We developed several
      bacterial and insect cell systems for expression of recombinant Arabidopsis
      thaliana PADOX1 and evaluated the enzyme's substrate and inhibitor profiles and
      explored the functional role of the amino-terminal domain. Substrate specificity
      studies gave the following relative oxygenase activity values: linolenate, 1.00;
      linoleate, 0.95; oleate, 0.84; palmitoleate, 0.69; myristate, 0.23; palmitate,
      0.17; and gamma-linolenate, 0.16. Methyl esters of myristate, linoleate and
      linolenate were not oxygenated. 3-Thiamyristate was the only oxygenase substrate
      that produced pronounced enzyme self-inactivation during catalysis. 3,4
      Dehydromyristate inactivated the oxygenase without appreciable oxygen
      consumption. Several compounds inhibited oxygenase activity, including catechol
      (K(i) approximately 90 microM), divalent zinc ion (K(i) approximately 50 microM),
      N,N,N',N'-tetramethyl-p-phenylenediamine (K(i) approximately 20 microM) and
      cyanide ion (K(i) approximately 5 microM). Zinc ion did not change the K(m)
      values for linoleate or oxygen, or the K(i) value for cyanide, indicating that
      zinc acts at a distinct site from the other compounds. Gel-filtration
      chromatography revealed considerable variation in oligomeric state of recombinant
      PADOX1 produced in the various expression systems, but oligomeric state was not
      correlated with activity. Deletion of the first eight or fourteen PADOX1 residues
      in a NuSA-PADOX1 fusion protein led to 13 and 83% decreases in activity,
      respectively, indicating the N-terminal region is important for normal catalytic
      activity.

PMID- 16889975
TI  - Regulatory mechanisms of ethylene biosynthesis in response to various stimuli
      during maturation and ripening in fig fruit (Ficus carica L.).
AB  - In order to obtain a greater uniformity of maturation, the growth of the fig
      fruit (Ficus carica L.) can be stimulated by the application of either olive oil,
      ethrel/ethephon or auxin. The three treatments induce ethylene production in
      figs. In this study, we investigated the regulatory mechanisms responsible for
      oil, auxin and ethylene induced ethylene production in figs. The ethylene
      production in response to olive oil, auxin, and propylene treatments and during
      ripening were all induced by 1-methylcyclopropene (1-MCP) and inhibited by
      propylene indicating a negative feedback regulation mechanism. Three 1
      aminocyclopropane-1-carboxylic acid (ACC) synthase genes (Fc-ACS1, Fc-ACS2 and Fc
      ACS3) and one ACC oxidase gene (Fc-ACO1) were isolated and their expression
      patterns in response to either oil, propylene or auxin treatment in figs
      determined. The expression patterns of Fc-ACS1 and Fc-ACO1 were clearly inhibited
      by 1-MCP and induced by propylene in oil treated and ripe fruits indicating
      positive regulation by ethylene, whereas Fc-ACS2 gene expression was induced by 1
      MCP and inhibited by propylene indicating negative regulation by ethylene. The Fc
      ACS3 mRNA showed high level accumulation in the auxin treated fruit. The
      inhibition of Fc-ACS3 gene by 1-MCP in oil treated and in ripe fruits suggests
      that auxin and ethylene modulate the expression of this gene by multi-responsive
      signal transduction pathway mechanisms. We further report that the olive oil
      induced ethylene in figs involves the ACC-dependent pathway and that multiple
      ethylene regulatory pathways are involved during maturation and ripening in figs
      and each specific pathway depends on the inducer/stimulus.

PMID- 16889976
TI  - Females and males of root-parasitic cyst nematodes induce different symplasmic
      connections between their syncytial feeding cells and the phloem in Arabidopsis
      thaliana.
AB  - Root syncytia induced by the beet cyst nematode Heterodera schachtii were thought
      to be symplasmically isolated. A recent study with mobile and immobile GFP
      constructs expressed in transgenic Arabidopsis plants under the control of
      pAtSUC2 showed that only mobile GFP could be detected in syncytia and suggested
      the existence of plasmodesmata between syncytia and the phloem. In the present
      study the existence of plasmodesmata between syncytia and the phloem is proven by
      grafting experiments. This technique rules out the possibility that GFP
      accumulation in syncytia is due to GFP expression in syncytia. Mobile GFP could
      be followed from transgenic scions carrying a pAtSUC2-gfp fusion construct via
      wild-type rootstocks into nematode-induced syncytia. While GFP could be detected
      in all syncytia associated to female nematodes, it was never observed in syncytia
      of male juveniles. As no GFP-mRNA could be detected in the rootstock we postulate
      that GFP as protein entered syncytia of females via plasmodesmata, while the
      protein was excluded from syncytia of male juveniles by plasmodesmata with a
      lower size exclusion limit.

PMID- 16889977
TI  - Arabidopsis thaliana wild type, pho1, and pho2 mutant plants show different
      responses to exogenous cytokinins.
AB  - Despite the involvement of cytokinins in phosphate (Pi) signaling being
      highlighted, the physiological processes involved remain unclear. In this study,
      we have evaluated the effect of cytokinins on different physiological responses
      using wild type (wt) and two Arabidopsis mutants with altered shoot Pi content
      (pho1 and pho2). Physiological studies were related with those previously
      described as cytokinin-regulated: including hypocotyl elongation, root growth,
      anthocyanin accumulation, senescence and relative gene expression. Generally,
      pho1 mutants showed decreased sensitivity to cytokinin, whereas pho2 mutants
      showed increased sensitivity to the hormone. This observation applies to
      inhibition of hypocotyls and root growth and anthocyanin accumulation. However,
      this effect was not shown during senescence or in the expression of ARR6
      (Arabidopsis response regulator, ARR). Interestingly, Pi content in shoot of pho1
      mutants increased to wt levels after treatment with cytokinins. These results
      suggest that the interaction between phosphate signaling and cytokinin signaling
      may be bidirectional while the differential behavior in response to cytokinin is
      discussed further.

PMID- 16889978
TI  - Effects of storage temperature on viability, germination and antioxidant
      metabolism in Ginkgo biloba L. seeds.
AB  - The behaviour of the Ginkgo biloba L. seeds was studied during storage at 4 and
      25 degrees C. When stored at 25 degrees C, all the seeds died in 6 months. Cold
      temperatures preserved seed tissue viability for 1 year but did not preserve
      their capability to germinate, since such capability decreased after 6 months. A
      significant increase in lipid peroxidation occurred in the seed both in the
      embryo and in the endosperm. During storage a progressive deterioration of the
      endosperm tissues was evident. The two major water soluble antioxidants,
      ascorbate (ASC) and glutathione (GSH), showed different behaviour in the two
      conditions of storage and in the two main structures of the seed, the embryo and
      the endosperm. The ASC content of embryos and endosperms remained quite unchanged
      in the first 9 months at 4 degrees C, then increased. At 25 degrees C a
      significant decrease in the ASC content in the embryos was evident, whereas it
      remained more stable in the endosperm. The GSH pool decreased at both storage
      temperatures in the embryos. As far as the ASC-GSH redox enzymes are concerned,
      their activities decreased with storage, but changes appeared to be time
      dependent more than temperature-dependent, with the exception of the endosperm
      ascorbate free radical (AFR) reductase (EC 1.6.5.4), the activity of which
      rapidly decreased at 25 degrees C. Therefore overall the antioxidant enzymes were
      scarcely regulated and unable to counteract oxidative stress occurring during the
      long-term storage.

PMID- 16889979
TI  - Purification and characterization of a functionally active Mycobacterium
      tuberculosis prephenate dehydrogenase.
AB  - Tuberculosis (TB) remains to be a global health problem. New drugs are badly
      needed to drastically reduce treatment time and overcome some of the challenges
      with tuberculosis treatment, such as multi-drug resistant (MDR) strain infected
      patients or tuberculosis/HIV co-infected patients. The essentiality of
      mycobacterial aromatic amino acid biosynthesis pathways and their absence from
      human host indicate that the member enzymes of these pathways promising drug
      targets for therapeutic agents against pathogen mycobacteria. Prephenate
      dehydrogenase (PDH) is a key regulatory enzyme in tyrosine biosynthesis,
      catalyzing the NAD(+)-dependent conversion of prephenate to p
      hydroxyphenylpyruvate, making it a potential drug target for antibiotics
      discovery. The recombinant PDH with an N-terminal His-tag (His-rMtPDH) was first
      purified in Escherichia coli, and using enterokinase rMtPDH was obtained by
      cleaving the N-terminal fusion partner. The effect of pH, temperature and the
      cation-Na(+) on purified enzyme activity was characterized. The N-terminal fusion
      partner was found to have little effect on the biochemical properties of PDH. We
      also provide in vitro evidence that Mycobacterium tuberculosis PDH does not
      possess any chorismate mutase (CM) activity, which suggests that, unlike many
      other enteric bacteria (where PDH exists as a fusion protein with CM), M.
      tuberculosis PDH is a monofunctional protein.

PMID- 16889981
TI  - Tracking peptide-membrane interactions: insights from in situ coupled confocal
      atomic force microscopy imaging of NAP-22 peptide insertion and assembly.
AB  - Elucidating the role that charged membrane proteins play in determining cell
      membrane structure and dynamics is an area of active study. We have applied in
      situ correlated atomic force and confocal microscopies to characterize the
      interaction of the NAP-22 peptide with model membranes prepared as supported
      planar bilayers containing both liquid-ordered and liquid-disordered domains. Our
      results demonstrated that the NAP-22 peptide interacts with membranes in a
      concentration-dependent manner, preferentially inserting into DOPC (ld) domains.
      While at low peptide concentrations, the NAP-22 peptide formed aggregate-like
      structures within the ld domains, at high peptide concentrations, it appeared to
      sequester cholesterol into the ld domains and recruited phosphatidyl-myo-inositol
      4,5-bisphosphate by inducing a blending effect that homogenizes the phase
      segregated domains into one liquid-ordered domain. This study describes a
      possible mechanism by which the NAP-22 peptide can affect neuronal morphology.

PMID- 16889980
TI  - Preparation of hepatitis C virus structural and non-structural protein fragments
      and studies of their immunogenicity.
AB  - Plasmids pQE-60 and pQE-30 containing 6 x His-tag sequence were used for
      expression of fragments of HCV structural and non-structural proteins in
      Escherichia coli (E. coli). The following fragments were used: core (1-98 aa),
      NS3 (202-482 aa), and tetramer of hypervariable region 1 (HVR1) of E2 protein.
      The constructed plasmids directed high levels of expression of HCV proteins in E.
      coli JM109. After purification by the metal-affinity chromatography on nickel
      nitrilotriacetic acid (Ni-NTA) agarose, the His-tagged HCV proteins were used for
      immunization of BALB/c mice. All three proteins were able to induce high levels
      of specific antibodies and, in the case of the NS3 and HVR1 tetramer, also to
      mount vigorous cell-proliferating responses. High immunogenicity of the tested
      fragments of HCV proteins shows them as good candidates for inclusion into the
      future HCV vaccine preparations.

PMID- 16889982
TI  - Effect of electrode location on EMG signal envelope in leg muscles during gait.
AB  - The aim of the study was to assess the variability of EMG signal envelope with
      electrode location during gait. Surface EMG signals were recorded from 10 healthy
      subjects from the tibialis anterior (TA), peroneus longus (PL), gastrocnemius
      medialis (GM), gastrocnemius lateralis (GL), and soleus (SO) muscles. From TA,
      PL, GL and GM, signals were acquired using a two-dimensional grid of 4 x 3
      electrodes (10 x 15 mm in size, as used in most gait laboratories) with 20-mm
      interelectrode distance in both directions. A similar grid of 3 x 3 electrodes
      was used for SO. EMG envelope was characterized by its peak value, area after
      normalization by the peak value, and time instant corresponding to the maximum.
      The maximum relative change in peak value with electrode location, expressed as a
      percentage of the peak value in the central location, was (mean+/-SD) 31+/-18%
      for TA, 29+/-13% for PL, 25+/-15% for GL, 14+/-8% for GM, and 26+/-14% for SO.
      The maximum relative change in area was 29+/-13% for TA, 73+/-40% for PL, 31+/
      23% for GL, 35+/-20% for GM, 20+/-13% for SO, and in the position of maximum,
      computed as distance from the maximum position in the central channel, it was 5+/
      10% of the gait cycle for TA, 26+/-16% for PL, 3+/-2% for GL, 3+/-1% for GM, 3+/
      3% for SO. A crosstalk index, defined on the basis of the expected intervals of
      muscle activation for healthy subjects, indicated that estimated crosstalk was
      present between TA and PL, in an amount which depended on electrode location. It
      was concluded that the estimate of muscle activation intensity during gait from
      surface EMG is variable with location of the electrodes while timing of muscle
      activity is more robust to electrode displacement and can be reliably extracted
      in those cases in which crosstalk is limited. These results are valid for healthy
      subjects, where the level of muscular activity during gait is much lower than
      maximum.

PMID- 16889983
TI  - Stepping from a narrow support.
AB  - The study addresses postural preparation to stepping. In particular, it tests a
      hypothesis that such preparation involves adjustments in the activity of ankle
      plantarflexors to produce shifts of the center of pressure. We investigated the
      initiation of a step from quiet stance when the subjects stood on boards with a
      decreased dimension of the support area in the anterior-posterior direction
      ("unstable boards"). Stepping from an unstable board was associated with
      decreased preparatory shifts of the center of pressure (COP) in the anterior
      posterior direction from about 3 cm to 0.9 cm and further to 0.1cm when the
      support narrowed from comfortable standing to 3.3 cm and to nearly 0 cm. There
      was a smaller decrease in the COP shift in the medio-lateral direction. When the
      subjects stood on a board which rested on a very narrow ridge ("zero-support"),
      they showed an increase in the magnitude of changes in the horizontal force
      immediately prior to making a step. There was a general increase in the level of
      activation of leg and trunk muscles during stepping from unstable boards. The
      modulation of the activity of ankle plantarflexors increased during stepping from
      unstable boards. We conclude that, to initiate a step, COP shifts and changes in
      shear force can be modulated independently of each other in a constraint-specific
      manner. The results speak against the hypothesis that modulation of ankle
      plantarflexor activity during postural adjustments is directly related to the
      production of COP shifts.

PMID- 16889984
TI  - Combining fMRI and MEG increases the reliability of presurgical language
      localization: a clinical study on the difference between and congruence of both
      modalities.
AB  - To avoid neurological impairment during surgery near language-related eloquent
      brain areas, we performed presurgical functional brain mapping with functional
      magnetic resonance imaging (fMRI) and magnetoencephalography (MEG) in 172
      patients using language tasks. For MEG localizations, we used either a moving
      equivalent-current dipole fit or a current-density reconstruction using a minimum
      variance beamformer with a spatial filter algorithm. We localized the Wernicke
      and Broca language areas for every patient. We integrated the results into a
      frameless stereotaxy system. To visualize the results in the navigation
      microscope during surgery, we superimposed the fMRI and MEG findings on the brain
      surface. MEG and fMRI results differed in 4% of cases, and in 19%, one modality
      showed activation but not the other. In the vicinity of large gliomas, the BOLD
      (blood oxygenation level-dependent) effect was suppressed in 53% of our patients.
      Of the 124 patients who had surgery, only 7 patients (5.6%) experienced a
      transient language deterioration, which resolved in all cases. We used MEG and
      fMRI to show different aspects of brain activity and to establish validation
      between MEG and fMRI. We conclude that measurement by both MEG and fMRI increases
      the degree of reliability of language area localization and that the combination
      of fMRI and MEG is useful for presurgical localization of language-related
      eloquent cortex.

PMID- 16889985
TI  - Changes in cerebral glucose utilization in patients with panic disorder treated
      with cognitive-behavioral therapy.
AB  - Several neuroanatomical hypotheses of panic disorder have been proposed focusing
      on the significant role of the amygdala and PAG-related "panic neurocircuitry."
      Although cognitive-behavioral therapy is effective in patients with panic
      disorder, its therapeutic mechanism of action in the brain remains unclear. The
      present study was performed to investigate regional brain glucose metabolic
      changes associated with successful completion of cognitive-behavioral therapy in
      panic disorder patients. The regional glucose utilization in patients with panic
      disorder was compared before and after cognitive-behavioral therapy using
      positron emission tomography with (18)F-fluorodeoxyglucose. In 11 of 12 patients
      who showed improvement after cognitive-behavioral therapy, decreased glucose
      utilization was detected in the right hippocampus, left anterior cingulate, left
      cerebellum, and pons, whereas increased glucose utilization was seen in the
      bilateral medial prefrontal cortices. Significant correlations were found between
      the percent change relative to the pretreatment value of glucose utilization in
      the left medial prefrontal cortex and those of anxiety and agoraphobia-related
      subscale of the Panic Disorder Severity Scale, and between that of the midbrain
      and that of the number of panic attacks during the 4 weeks before each scan in
      all 12 patients. The completion of successful cognitive-behavioral therapy
      involved not only reduction of the baseline hyperactivity in several brain areas
      but also adaptive metabolic changes of the bilateral medial prefrontal cortices
      in panic disorder patients.

PMID- 16889986
TI  - Allelic expression analysis suggests that cis-acting polymorphism of FRZB
      expression does not contribute to osteoarthritis susceptibility.
AB  - OBJECTIVE: The FRZB gene codes for secreted frizzled-related protein 3 (sFRP3), a
      soluble antagonist of wnt signalling that is required for maintaining cartilage
      integrity. Two common single nucleotide polymorphisms (SNPs) that code for the
      substitution of conserved arginine residues have previously been identified in
      FRZB and found to be associated with osteoarthritis (OA). Functional studies
      revealed that the arginine substitutions lead to a loss-of-function of sFRP3
      activity. We set out to assess whether cis-acting polymorphism in the regulation
      of FRZB expression exists, as this may be an additional mechanism through which
      sFRP3 activity could be modulated. METHODS: RNA was extracted from the articular
      cartilage chondrocytes of 25 individuals who had undergone joint replacement for
      OA and who were heterozygous for one of the two FRZB SNPs. Allelic output was
      measured by single base extension in to the SNPs and deviations from the expected
      1:1 pattern were assessed using the Mann-Whitney U test. RESULTS: Differential
      allelic expression was observed in six of the 25 individuals. However, the
      average fold difference in allelic expression in the six was only 1.19.
      CONCLUSIONS: The presence of a small degree of differential allelic expression in
      a low proportion (24%) of the individuals studied suggests that polymorphism in
      FRZB cis-acting regulatory elements can be discounted as a major factor that
      could influence the development of OA.

PMID- 16889987
TI  - A forskolin derivative, FSK88, induces apoptosis in human gastric cancer BGC823
      cells through caspase activation involving regulation of Bcl-2 family gene
      expression, dissipation of mitochondrial membrane potential and cytochrome c
      release.
AB  - FSK88, a forskolin derivative, was extracted and purified from cultured tropical
      plant roots, Coleus forskohlii. Our previous studies have demonstrated that FSK88
      can inhibit HL-60 cell proliferation and induce the differentiation of HL-60
      cells to monocyte macrophages. In this study, we showed that FSK88 can induce
      apoptotic death of human gastric cancer BGC823 cells in a dose- and time
      dependent manner. Results showed that FSK88-induced apoptosis was accompanied by
      the mitochondrial release of cytochrome c and activation of caspase-3 in BGC823
      cells. Furthermore, treatment with caspase-3 inhibitor (z-DEVD-fmk) was capable
      of preventing the FSK88-induced caspase-3 activity and apoptosis. FSK88-induced
      apoptosis in human gastric cancer BGC823 cells was also accompanied by the up
      regulation of Bax, Bad and down-regulation of Bcl-2. Theses results clearly
      demonstrated that the induction of apoptosis by FSK88 involved multiple cellular
      and molecular pathways and strongly suggest that pro- and anti-apoptotic Bcl-2
      family genes, mitochondrial membrane potential (Deltapsi(m)), cytochrome c, and
      caspase-3, participate in the FSK88-induced apoptotic process in human gastric
      cancer BGC823 cells.

PMID- 16889988
TI  - Gene silencing analyses against amyloid precursor protein (APP) gene family by
      RNA interference.
AB  - Amyloid precursor protein (APP) and amyloid precursor-like proteins 1 and 2
      (APLP1 and APLP2) are members of a large gene family. Although APP is known to be
      the source of the beta-amyloid peptides involved in the development of
      Alzheimer's disease, the normal functions of APP, APLP1 and APLP2 in cells are
      poorly understood. In this study, we carried out gene silencing analysis by means
      of RNA interference with synthetic small interfering RNA duplexes targeting the
      App, Aplp1 and Aplp2 genes in Neuro2a (N2a) cells, a mouse neuroblastoma cell
      line. The results demonstrated that cell viability and neurite outgrowth of N2a
      cells undergoing knockdown of Aplp1 were significantly reduced, compared with N2a
      cells undergoing knockdown of either App or Aplp2.

PMID- 16889989
TI  - alphaII-Spectrin interacts with five groups of functionally important proteins in
      the nucleus.
AB  - Nonerythroid alpha-spectrin (alphaSpIISigma( *)) is a structural protein that has
      been identified in the nucleus of mammalian cells and shown to be involved in DNA
      repair. It is also deficient in cells from the clinically diverse genetic
      disorder Fanconi anemia (FA). In order to get a clearer understanding of the role
      of alphaSpIISigma( *) in DNA repair, and whether it may have other important
      functions in the nucleus, studies were undertaken to identify specific
      alphaSpIISigma( *) protein binding partners in the nucleus. The results
      demonstrate that multiple proteins co-immunoprecipitate with alphaSpIISigma( *)
      from nuclear extracts from normal human lymphoblastoid and HeLa cells. These can
      be grouped into five categories: structural proteins, proteins involved in DNA
      repair, chromatin remodeling proteins, FA proteins, and transcription and RNA
      processing factors. These studies indicate that alphaSpIISigma( *) may play a
      role in a number of diverse and important processes in the nucleus and that a
      deficiency in this protein, as occurs in FA, could affect a number of critical
      cellular pathways.

PMID- 16889990
TI  - Effects of extremely low concentrations of hormones on the insulin binding of
      Tetrahymena.
AB  - FITC-insulin binding to previously hormone-treated Tetrahymena was studied by
      flow cytometry and confocal microscopy. Hormones produced by Tetrahymena were
      chosen for study and the hormone concentrations were administered between 10(-6)
      and 10(-21)M for 30 min. Endorphin, serotonin and insulin significantly reduced
      the hormone binding however histamine did not influence it at all. Endorphin,
      serotonin and insulin were significantly effective down to 10(-18)M and the
      effect of insulin and endorphin suggest a similar mechanism. The results call
      attention to the efficacy of very low hormone concentrations, which can influence
      the hormone content (earlier experiments) and receptor binding capacity (present
      study) of a unicellular organism. This seems to be very important, as in wild
      (natural) conditions the dilution of signaling materials secreted by a water
      living protozoan is very high. In addition, the results point to the selectivity
      of response, as not all of the hormones that deeply influence other physiological
      indices (e.g. histamine) have an effect on insulin content or insulin receptors.

PMID- 16889991
TI  - Acute glucose overload potentiates nitric oxide production in lipopolysaccharide
      stimulated macrophages: the role of purinergic receptor activation.
AB  - The positive effects of high glucose on the cellular productivity of nitric oxide
      (NO), and the mechanisms of the enhancement, were investigated. Macrophages were
      shifted from normal-glucose medium (5.5 mM) to high-glucose medium (25 mM) and
      immediately treated with lipopolysaccharide (LPS). Inducible nitric oxide
      synthase (iNOS) expression was expressed significantly more quickly, and NO
      production also increased. High-glucose conditions reduced cell viability at 48
      h. Pretreatment with oxidized adenosine triphosphate (o-ATP), the selective
      purinergic receptor antagonist, strongly reduced LPS-induced iNOS expression, NO
      production and cell death in cells exposed to high levels of glucose. Apyrase, an
      ATP-hydrolyzing enzyme, also reduced the effects of high-glucose content. High
      glucose content promoted the LPS-induced release of endogenous ATP from RAW 264.7
      cells, as measured by luciferin-luciferase assay. In summary, the results
      revealed that purinergic receptor is important in responding to LPS challenge,
      increasing LPS-induced NO production and cell death under high-glucose
      conditions, and promoting the release of ATP from macrophages in high-glucose
      medium.

PMID- 16889992
TI  - Effect of betamethasone in vivo on placental adrenomedullin in human pregnancy.
AB  - OBJECTIVE: The aim of the current study was to determine the effects of in vivo
      administration of prenatal betamethasone in patients at risk for preterm delivery
      on adrenomedullin (AM) concentrations in maternal and fetal plasma and on AM
      localization in placenta and fetal membranes. METHODS: A total of 62 pregnant
      women between 25 and 35 weeks' gestation were studied. Forty-seven pregnant women
      received betamethasone (2 x 12 mg intramuscularly given 24 hours apart) for
      stimulation of fetal lung maturity. Blood samples were collected before
      betamethasone administration and at different time points after the first and the
      second dose. Further samples were collected at delivery and, in women who did not
      deliver, after 1 week and 30 days from betamethasone administration. At delivery,
      placenta and membranes were collected. Fifteen patients who delivered at the same
      gestational age not receiving betamethasone represented the control group. AM
      concentration was determined by radioimmunoassay. Localization of AM in placental
      tissues was assessed by immunohistochemistry. RESULTS: Betamethasone caused
      approximately 50% increase in maternal plasma AM at 1 week after administration,
      whereas in fetal plasma AM levels increased by about 90% at 48 hours after
      betamethasone administration. There was increased immunohistochemical staining
      for AM in fetoplacental tissues collected after betamethasone administration.
      CONCLUSION: These results provide the first evidence for in vivo stimulation of
      AM, likely of placental origin, by glucocorticoids in the third trimester human
      pregnancy.

PMID- 16889994
TI  - Dynamic connectivity in the mitral cell-granule cell microcircuit.
AB  - The interactions between excitatory mitral cells and inhibitory granule cells are
      critical for the regulation of olfactory bulb activity. Here we review anatomical
      and physiological data on the mitral cell-granule cell circuit and provide a
      quantitative estimate of how this connectivity varies as a function of distance
      between mitral cells. We also discuss the ways in which the functional
      connectivity can be altered rapidly during olfactory bulb activity.

PMID- 16889993
TI  - Racial differences in the prevalence of Factor V Leiden mutation among patients
      on chronic warfarin therapy.
AB  - We report the prevalence of Factor V Leiden (FVL) in European American and
      African American patients on warfarin therapy residing in Alabama. METHODS.:
      Detailed history was obtained and FVL genotype was determined for 288 patients
      enrolled in a prospective cohort: Pharmacogenetic Optimization of Anticoagulation
      Therapy. Racial differences in genotype frequency were assessed by the Chi-square
      statistics and HWE assumptions by G-statistics. Race-specific analysis for the
      association between site of thromboembolism and the presence of FVL mutation was
      assessed using logistic regression. RESULTS.: The overall heterozygote (GA
      genotype) frequency was 4.9%. No patient was found to be homozygous (AA) for the
      variant allele. The prevalence of GA was higher in European American (8.6%)
      compared to African American (1.4%) patients (p=0.004). The FVL genotype
      frequency was significantly different across race for venous thromboembolic
      events (p=0.014) but not for arterial thromboembolic events (p=0.20).
      Multivariable race-specific analysis highlights the contribution of FVL mutation
      to the risk of venous thromboembolic events in European American (p=0.03) but not
      in African American patients (p=0.95). European American patients with the GA
      mutation were approximately 6.3 times more likely to have experienced a venous,
      rather than arterial thromboembolic event. CONCLUSION.: In Alabama, among
      patients on warfarin, the GA genotype is more prevalent in European Americans
      compared to African Americans. In European Americans, but not in African
      Americans, the GA genotype was more prevalent in patients with venous compared to
      arterial thromboembolic events.

PMID- 16889995
TI  - The NOS3 (27-bp repeat, intron 4) polymorphism is associated with susceptibility
      to osteomyelitis.
AB  - Cytokines generate nitric oxide (NO) in osteoblasts and neutrophils through the
      induction of NO synthase isoforms, endothelial (NOS3) and inducible (NOS2),
      thereby producing bone loss. In osteomyelitis (OM), a chronic infection of the
      bone, homozygosity for the NOS3 (27-bp repeat, intron 4 polymorphism) 4 allele
      was significantly more frequent among the 80 patients than in 300 healthy
      controls (p=0.044). No significant differences were found for other polymorphisms
      of the NOS genes such as NOS3, the promoter (-786T/C), and the missense change
      (E298D) in exon 7, and for NOS2, the G/A substitution at position 37498 in exon
      22, the (CCTTT)(n), and (TAAA)(n) micro-satellites and the -954G/C in the
      promoter. Serum NO levels were significantly higher only in the OM patients
      homozygous for the NOS3 (27-bp repeat, intron 4 polymorphism) 4 allele, compared
      to controls. In the presence of bacteria or bacterial products, the neutrophils
      of these patients produced more NO. However, immunolabelling of osteoblasts for
      NOS3 in biopsy tissues did not correlate with the carriage of a determined NOS
      polymorphism but with the presence of bone inflammation. This is the first report
      of an association between a NOS3 polymorphism and the risk of developing OM.

PMID- 16889996
TI  - Protective effect of Hypericum perforatum in zymosan-induced multiple organ
      dysfunction syndrome: relationship to its inhibitory effect on nitric oxide
      production and its peroxynitrite scavenging activity.
AB  - Hypericum perforatum is a medicinal plant species containing many polyphenolic
      compounds, namely flavonoids and phenolic acids. Since polyphenolic compounds
      have high antioxidant potential, we have investigated the effects of H.
      perforatum extract on the development of multiple organ dysfunction syndrome
      caused by zymosan (500 mg/kg, administered i.p. as a suspension in saline) in
      mice. Organ failure and systemic inflammation in rats was assessed 18 h after
      administration of zymosan and/or H. perforatum extract and monitored for 12 days
      (for loss of body weight and mortality). Treatment of mice with H. perforatum
      extract (30 mg/kg i.p., 1 and 6h after zymosan) attenuated the peritoneal
      exudation and the migration of polymorphonuclear cells caused by zymosan,
      pulmonary, intestinal and pancreatic injury, and renal dysfunction as well as the
      increase in myeloperoxidase in the lung and intestine. Immunohistochemical
      analysis for inducible nitric oxide synthase (iNOS), nitrotyrosine, and poly(ADP
      ribose) (PAR) revealed positive staining in lung and intestine tissues obtained
      from zymosan-injected mice. The degree of staining for nitrotyrosine, iNOS, and
      PAR was markedly reduced in tissue sections obtained from zymosan-treated mice,
      which received H. perforatum extract. In conclusion, this study provides
      evidence, for the first time, that H. perforatum extract attenuates the degree of
      zymosan-induced multiple organ dysfunction syndrome in mice.

PMID- 16889997
TI  - Nitric oxide (NO) is a new clinical biomarker of survival in the elderly patients
      and its efficacy might be nearly equal to albumin.
AB  - BACKGROUND: For elderly patients, the consideration of prognostic factors is very
      important, but there have been few reports about the potential use of vasoactive
      substances as prognostic markers in the elderly. OBJECTIVE: We assessed
      endocrinological substances, such as plasma NO(x) (metabolites of NO), as the
      prognostic marker in elderly. We compared their efficacy with that of such well
      known markers as albumin and pro-inflammatory cytokines such as IL-6. METHODS:
      The patients were recruited consequently from the clinics of Nagoya University
      Hospital or related home care services facilities. One hundred and twenty seven
      elderly aged 65 and older were registered. Biochemical analyses such as albumin,
      total cholesterol, BNP, and NO(x) were measured upon enrollment. The main outcome
      was the survival rate. RESULTS: Forty-six patients died during the follow-up
      period. Mann-Whitney's U-test showed that the levels of age, hemoglobin, total
      protein, serum albumin, serum creatinine, total cholesterol, HDL-cholesterol, LDL
      cholesterol, high sensitive CRP, NO(x), IL-6, and TNF-alpha were significantly
      different between the living and deceased subjects. Among the dependent variables
      in the logistic regression analyses, only albumin and NO(x) were significantly
      different. In the Kaplan-Meier analyses of mortality, the prognosis of patients
      in 3rd and 4th quartile of NO(x) was significantly worse than that in 1st or 2nd
      quartile. CONCLUSION: NO(x) has potential both as a vascular marker and as a
      marker for predicting survival in elderly. In the latter role, it may be as
      effective as albumin.

PMID- 16889998
TI  - Heterotopic noxious conditioning stimulation (HNCS) reduced the intensity of
      spontaneous pain, but not of allodynia in painful peripheral neuropathy.
AB  - In 15 patients with painful peripheral neuropathy and dynamic mechanical
      allodynia, the influence of spontaneous ongoing neuropathic pain on pain
      sensitivity in a remote pain-free area was examined, as was the influence of
      ischemia-induced heterotopic noxious conditioning stimulation (HNCS) on the
      intensity of ongoing pain and brush-evoked allodynia. In addition, the modulating
      effect of HNCS on pain sensitivity in a pain-free area was investigated. Pain
      thresholds to pressure and heat as well as the sensitivity to suprathreshold
      pressure- and heat pain were assessed in the pain-free area. Dynamic mechanical
      allodynia was induced by a recently developed semi-quantitative brushing
      technique and the patients continuously rated the intensity of the allodynia
      using a computerized visual analogue scale (VAS). The total brush-evoked pain
      intensity was calculated as the area under the VAS curve. At baseline, no
      significant difference in pain sensitivity was found between patients and their
      healthy controls in the pain-free area, indicating a lack of activation of pain
      modulatory systems from the spontaneous pain. Compared to baseline, the patients
      rated the ongoing neuropathic pain intensity significantly lower during the HNCS
      procedure (p<0.05). In contrast, there was no influence from HNCS on the total
      brush-evoked pain intensity. In the pain-free area higher pressure pain
      thresholds were demonstrated during conditioning stimulation in patients and
      controls alike (p<0.01). In controls only, a significantly higher heat pain
      threshold was found during the HNCS-procedure (p<0.01). The main finding of the
      present study was that HNCS altered differentially spontaneous and brush-provoked
      pain in patients with painful peripheral neuropathy.

PMID- 16889999
TI  - Effect of hypnotic suggestion on fibromyalgic pain: comparison between hypnosis
      and relaxation.
AB  - The main aims of this experimental study are: (1) to compare the relative effects
      of analgesia suggestions and relaxation suggestions on clinical pain, and (2) to
      compare the relative effect of relaxation suggestions when they are presented as
      "hypnosis" and as "relaxation training". Forty-five patients with fibromyalgia
      were randomly assigned to one of the following experimental conditions: (a)
      hypnosis with relaxation suggestions; (b) hypnosis with analgesia suggestions;
      (c) relaxation. Before and after the experimental session, the pain intensity was
      measured using a visual analogue scale (VAS) and the sensory and affective
      dimensions were measured with the McGill Pain Questionnaire. The results showed:
      (1) that hypnosis followed by analgesia suggestions has a greater effect on the
      intensity of pain and on the sensory dimension of pain than hypnosis followed by
      relaxation suggestions; (2) that the effect of hypnosis followed by relaxation
      suggestions is not greater than relaxation. We discuss the implications of the
      study on our understanding of the importance of suggestions used in hypnosis and
      of the differences and similarities between hypnotic relaxation and relaxation
      training.

PMID- 16890000
TI  - Relationship between susceptibility induced field inhomogeneities, restricted
      diffusion, and relaxation in sedimentary rocks.
AB  - Low field relaxation and diffusion measurements have become essential tools to
      study the pore space of sedimentary rocks with important practical applications
      in the field of well logging and hydrocarbon extractions. Even at Larmor
      frequencies below 2 MHz, diffusion measurements are often affected noticeably by
      internal field inhomogeneities. These field inhomogeneities are induced by
      susceptibility contrast between the rock and the fluid and are evident in most
      sandstones. Using sets of two-dimensional diffusion-relaxation measurements in
      applied and internal gradients, we study in detail the correlation between the
      field inhomogeneities, restricted diffusion, and relaxation time in three rocks
      of different susceptibility. We find that in the sandstone cores, the field
      inhomogeneities in large pores can be described by a local gradient that scales
      inversely with relaxation time above 250 ms. At shorter relaxation times, the
      extracted internal gradients deviate from this scaling relationship and we
      observe a dependence on diffusion time. This demonstrates that in this case, the
      internal field has structure on a length scale of a few microns.

PMID- 16890001
TI  - IDEAL-A fast single scan method for X pulse width calibration.
AB  - In line with the recent development of the rapid single scan technique to
      calibrate proton flip angle, a new method that allows calibration of X-nucleus
      pulse width in a single scan is presented. The method involves observation of the
      anti-phase coherence of a proton coupled to a hetero-nuclear X-spin with nutation
      pulses applied at the X-spin resonance frequency in a gated decoupling
      experiment. The X-spin nutation causes the well-known illusions of decoupling,
      enabling estimation of rf amplitude level and the method is, thus, dubbed as
      IDEAL.

PMID- 16890002
TI  - Statistical external validation and consensus modeling: a QSPR case study for Koc
      prediction.
AB  - The soil sorption partition coefficient (log K(oc)) of a heterogeneous set of 643
      organic non-ionic compounds, with a range of more than 6 log units, is predicted
      by a statistically validated QSAR modeling approach. The applied multiple linear
      regression (ordinary least squares, OLS) is based on a variety of theoretical
      molecular descriptors selected by the genetic algorithms-variable subset
      selection (GA-VSS) procedure. The models were validated for predictivity by
      different internal and external validation approaches. For external validation we
      applied self organizing maps (SOM) to split the original data set: the best four
      dimensional model, developed on a reduced training set of 93 chemicals, has a
      predictivity of 78% when applied on 550 validation chemicals (prediction set).
      The selected molecular descriptors, which could be interpreted through their
      mechanistic meaning, were compared with the more common physico-chemical
      descriptors log K(ow) and log S(w). The chemical applicability domain of each
      model was verified by the leverage approach in order to propose only reliable
      data. The best predicted data were obtained by consensus modeling from 10
      different models in the genetic algorithm model population.

PMID- 16890003
TI  - Variability of taurine concentrations in Mytilus galloprovincialis as a function
      of body size and specific tissue.
AB  - Variability of taurine (2-aminoethane sulfonic acid) was studied as a function of
      size in the mussel Mytilus galloprovincialis and tissue specificity. Isometric
      and/or allometric relationships were established with regard to total soft mass
      of the mussels between 20 and 60 mm shell length. Relative amounts of taurine
      dropped significantly with increasing mass of whole soft tissues with an
      allometric coefficient value of -0.15. The inverse relationship between taurine
      and increasing size of mussels was confirmed for gill epithelium and labial palp
      (allometric coefficient values of -0.16 and -0.10, respectively), tissues that,
      in turn, represented isometric functions with regard to total soft mass. Although
      relative amounts of taurine were significantly different in digestive gland,
      mantle and foot, relationships with increasing size of mussels remained unchanged
      in these tissues. Gill area of mussels was related to soft mass with an
      allometric coefficient of 0.70 by 2D Image Analysis, but increased to 0.85 when
      introducing a third dimension, i.e. gill thickness. Results are discussed
      according to gill structure analysis and taurine functionality.

PMID- 16890004
TI  - Metabolic engineering of Agrobacterium sp. for UDP-galactose regeneration and
      oligosaccharide synthesis.
AB  - Curdlan-producing Agrobacterium sp. is unique in possessing a highly efficient
      UDP-glucose regeneration system. A broad-host-range expression strategy was
      successfully developed to exploit the unique metabolic capability for UDP
      galactose regeneration during oligosaccharide synthesis. The engineered
      Agrobacterium cells functioned as a UDP-galactose regeneration system, allowing
      galactose-containing disaccharides to be synthesized from glucose or other simple
      sugars. Unexpectedly, a lag period of 24h preceded the active synthesis, which
      could be eliminated with rifampicin. An intracellular nucleotide profiling
      revealed that the UMP level was elevated by 3.8 fold in the presence of
      rifampicin, suggesting that rifampicin simulated a nitrogen-limitation condition
      that triggered the metabolic change. Product selectivity was improved nearly 40
      fold by using high acceptor concentration and restricting glucose supply. N
      acetyllactosamine concentration near 20 mM (7.5 g/l) was obtained, demonstrating
      the effectiveness of the engineered strain in UDP-galactose regeneration. This
      organism could be engineered to regenerate other UDP-sugar nucleotides using the
      same strategy as illustrated here.

PMID- 16890005
TI  - [Function preserving surgery of limb sarcomas: history and improvements].
AB  - In the seventies, limb-sparing surgery and radiation therapy appeared capable of
      successfully treating the great majority of adult patients with soft tissue
      sarcomas of the extremities. No survival benefit could be demonstrated in the
      patients selected for amputation. Microscopically positive surgical margins are
      related to a greater risk of local recurrence, whereas overall survival is
      compromised by high grade and large tumor size. Presurgery multidisciplinary
      discussion, management in reference center and management within cancer network
      independently predict conformity to the clinical practice guidelines. Reoperation
      should be a planned part of definitive management whenever the initial surgical
      procedure was done without a histologic diagnosis or was not planned to be a wide
      excision. Soft tissue flap reconstruction facilitates therapy for patients with
      locally advanced tumors so that patients with larger tumors can undergo
      resection, limiting complications and limb sacrifice. Vascular reconstruction is
      a feasible option in case of involvement of major vessels. Isolated limb
      perfusion (ILP) with TNF and chemotherapy is an efficient limb-sparing
      neoadjuvant therapy for locally advanced limb soft tissue sarcomas. Efficacy and
      safety of low-dose TNFalpha could greatly facilitate ILP procedures in the near
      future.

PMID- 16890007
TI  - Schwarz meets Schwann: design and fabrication of biomorphic and durataxic tissue
      engineering scaffolds.
AB  - Tissue engineering is a discipline at the leading edge of the field of computer
      assisted intervention. This multidisciplinary engineering science attempts to
      meet the reparative and regenerative needs of tissues and organs based on the
      notion of design and fabrication of scaffolds- porous, three-dimensional "trellis
      like" biomimetic structures that, on implantation, provide a viable environment
      to recuperate and regenerate damaged cells. Existing scaffold fabrication
      strategies produce sub-optimal porous labyrinths with contra-naturam straight
      edges. The biomorphic geometry that mimics the secundam-naturam substrate would
      be one that is continuous through all space, partitioned into two not-necessarily
      equal sub-spaces by a non-intersecting, two-sided surface. Minimal surface
      geometry is not only ideal to describe such a space but is also the
      preferentially assumed geometry in natural and pathological or manipulated cells.
      We present results on the premier attempt in computer-controlled fabrication,
      modulation, and mechanical characterization of tissue engineering scaffolds based
      on triply periodic minimal surfaces (TPMS). We also present novel strategies to
      realize coterminous seeding-feeding networks thereby guaranteeing blood/nutrient
      supply to the proliferating cells at close proximity. This initiative of linking
      Schwann's 1838 cell theory with Schwarz's 1865 discovery of TPMS is a significant
      step to fabricate the previously elusive optimal biomorphic tissue analogs.

PMID- 16890006
TI  - [Retrospective analysis of 108 ductal carcinomas in situ of the breast treated by
      radiosurgery association].
AB  - PURPOSE: To evaluate survival and prognostic factors of 108 patients with
      clinically or mammographically detected ductal carcinoma in situ (DCIS), treated
      from 1980 to 1996 by complete local excision followed by external irradiation.
      PATIENTS AND METHODS: The median age was 51 (range 37-80). All the patients
      underwent surgery consisting of a wide resection of the mammary gland harbouring
      the tumour. The surgical specimens were sent to the pathologists to get
      information on histology and margin clearance; all the slides were reviewed by
      one of us to assess the tumoral diameter. External beam therapy was delivered
      within 8 weeks after surgery. The prescribed irradiation dose was 50 Gy in 25
      fractions to be given in 5 weeks. The median duration of follow-up was 93 months
      (range 40-173). RESULTS: There were nine patients with local recurrence (8.3%);
      three patients had local recurrence of DCIS and six patients developed invasive
      breast cancer. The treatment of local recurrence consisted of mastectomy with or
      without axillary dissection (eight cases) and quadrantectomy (one case). The 5
      year and 10-year ipsilateral recurrence-free rate was respectively 92 and 89%.
      The 10-year cause specific survival was 100%. In univariate analysis, size>or=10
      mm, age<45 years old and margin status were significant P=0,02, P=0,03, P=0,005;
      margin status was significant in multivariate analysis (P<0,02). CONCLUSION:
      These results are in keeping with those of the literature. They could be improved
      by the mass screening campaign, which is going on since January 1990 among women
      aged 50-74 years.

PMID- 16890008
TI  - The biological cost of mutational antibiotic resistance: any practical
      conclusions?
AB  - A key parameter influencing the rate and trajectory of the evolution of
      antibiotic resistance is the fitness cost of resistance. Recent studies have
      demonstrated that antibiotic resistance, whether caused by target alteration or
      by other mechanisms, generally confers a reduction in fitness expressed as
      reduced growth, virulence or transmission. These findings imply that resistance
      might be reversible, provided antibiotic use is reduced. However, several
      processes act to stabilize resistance, including compensatory evolution where the
      fitness cost is ameliorated by additional mutation without loss of resistance,
      the rare occurrence of cost-free resistance mechanisms and genetic linkage or co
      selection between the resistance markers and other selected markers. Conceivably
      we can use this knowledge to rationally choose and design targets and drugs where
      the costs of resistance are the highest, and where the likelihood of compensation
      is the lowest.

PMID- 16890009
TI  - Microbial genomes and vaccine design: refinements to the classical reverse
      vaccinology approach.
AB  - The advent of whole-genome sequencing of bacteria and advances in bioinformatics
      have revolutionized the study of bacterial pathogenesis, enabling the targeting
      of possible vaccine candidates starting from genomic information. Nowadays, the
      availability of hundreds of bacterial genomes enables identification of the
      genetic differences across several genomes from the same species. The unexpected
      degree of intra-species diversity suggests that a single genome sequence is not
      entirely representative and does not offer a complete picture of the genetic
      variability of a species. The practical consequence is that, in many cases, a
      universal vaccine is possible only by including a combination of antigens and
      this combination must take into account the pathogen population structure.

PMID- 16890010
TI  - Characterisation of small double stranded RNA molecule in Cryptosporidium
      hominis, Cryptosporidium felis and Cryptosporidium meleagridis.
AB  - Coding regions of double stranded RNA molecules from 3 human faecal samples
      containing Cryptosporidium hominis, C. felis and C. meleagridis were
      characterised by sequencing and compared with that previously obtained for C.
      parvum. Sequences outside the coding regions were also obtained. Overall
      similarities of between 86% and 92% and between 86% and 93% were observed in the
      nucleotide and amino acid sequences respectively between these species. These
      larger sequences will allow further molecular tools for detection, identification
      and characterisation of Cryptosporidium spp.

PMID- 16890011
TI  - Synthesis and photophysical processes of 9-bromo-10-naphthalen-2-yl-anthracene.
AB  - A novel luminescent compound, 9-bromo-10-naphthalen-2-yl-anthracene (BNA) is
      synthesized by Suzuki Cross-coupling reaction of 9-bromo-anthracene and
      naphthalene-2-boronic acid. The structure is characterized by (1)H NMR, IR and UV
      vis spectroscopy. The photophysical processes of 9-bromo-10-naphthalen-2-yl
      anthracene have been carefully investigated by UV-vis absorption and fluorescence
      spectra. The results show that the compound emits blue and blue-violet light. The
      emission spectra exhibit obvious solvent effect. With the difference in polarity
      of solvents, The emission spectra is not only slightly blue shift with the
      increase of the solvent polarity but also change on the intensity of fluorescence
      at room temperature . The light emitting can be quenched by electron donor, N,N
      dimethylaniline (DMA). On adding gradually DMA into the solution of BNA, the
      emission intensities of fluorescence are gradually decreased. The quenching
      effect follows the Stern-Volmer equation.

PMID- 16890012
TI  - Auditory perception and attention as reflected by the brain event-related
      potentials in children with Asperger syndrome.
AB  - OBJECTIVE: Language development is delayed and deviant in individuals with
      autism, but proceeds quite normally in those with Asperger syndrome (AS). We
      investigated auditory-discrimination and orienting in children with AS using an
      event-related potential (ERP) paradigm that was previously applied to children
      with autism. METHODS: ERPs were measured to pitch, duration, and phonetic changes
      in vowels and to corresponding changes in non-speech sounds. Active sound
      discrimination was evaluated with a sound-identification task. RESULTS: The
      mismatch negativity (MMN), indexing sound-discrimination accuracy, showed right
      hemisphere dominance in the AS group, but not in the controls. Furthermore, the
      children with AS had diminished MMN-amplitudes and decreased hit rates for
      duration changes. In contrast, their MMN to speech pitch changes was parietally
      enhanced. The P3a, reflecting involuntary orienting to changes, was diminished in
      the children with AS for speech pitch and phoneme changes, but not for the
      corresponding non-speech changes. CONCLUSIONS: The children with AS differ from
      controls with respect to their sound-discrimination and orienting abilities.
      SIGNIFICANCE: The results of the children with AS are relatively similar to those
      earlier obtained from children with autism using the same paradigm, although
      these clinical groups differ markedly in their language development.

PMID- 16890013
TI  - Interpretation of the repetitive nerve stimulation test results using principal
      component analysis.
AB  - OBJECTIVE: Assessment of the repetitive nerve stimulation (RNS) test parameters
      has some inherent difficulties, as too many co-dependent variables are involved.
      To circumvent these problems, we have employed the principal component analysis
      (PCA) for evaluating the RNS test. METHODS: We performed the RNS test on the
      abductor digiti quinti (ADQ), flexor carpi ulnaris (FCU) and orbicularis oculi
      (OO) muscles of 23 myasthenia gravis (MG) patients and 50 controls. For each
      group, following parameters were chosen for PCA: decremental response of
      amplitude and area on 2, 3 and 5Hz stimulation rate, including 5Hz stimulation,
      4min following tetanus; decremental and incremental response of amplitude and
      area on 50Hz stimulation. RESULTS: Two principal components (PC1 and PC2) for ADQ
      and FCU muscles and 1 principal component (PC1) for OO muscle were extracted. The
      mean values of PC1 were significantly increased for all three muscles in the MG
      group compared to controls (p<0.01). No significant difference between PC2 values
      of the MG and control groups was observed (p>0.05). PC1 was the most sensitive
      test in detecting an abnormality on low rates of stimulation. CONCLUSIONS: PCA,
      which has the advantage of studying a small number of independent parameters on
      RNS test, seems to be useful for detecting neuromuscular transmission defects.
      SIGNIFICANCE: By markedly decreasing the number of assessed variables, PCA can
      give insight to the direction of data distribution abnormalities in the RNS test,
      which can prove particularly useful in research studies.

PMID- 16890015
TI  - The university-promoted patent at the crossroads of the research results and
      immediate industrial use.
AB  - The departments, indeed the laboratories of the public research institutions, no
      longer are satisfied with displaying a certain number of annual scientific
      publications meant to highlight their expertise and know-how. In effect, for some
      years now, a new trend has been in vogue: stimulated by all the national and
      international public bodies, they are calling increasingly on the "patent
      pending" solution to make optimum use of the results of specific researches on
      the one hand and, on the other hand, to assert their excellence vis-a-vis the
      Ministry of Research of their country which is supposed to finance them. However,
      caught up in the euphoria of the research results, and lost in their formulae and
      practices, these researchers lose sight of the basis for a patent and its real
      reason for being (patent charter). A patent necessarily must be of service to the
      community, that is to say that essentially it must contribute to the improvement
      of the quality of life of the population. To achieve this goal, going through
      certain stages is a must, namely that to start with a patent must be absolutely
      profitable to industry in order that, subsequently, it be consistent with its
      being of service to the community. In this context, its validity is set at 10
      years renewable for another 10 years based on specific parameters as stipulated
      by the national and international patent institutions, indeed by the EPO
      (European Patent Office) the headquarters of which is in Munich. Its use by
      industry ensures proceeds for 10, even 20 years and must represent the material
      fruit of the applicant's effort. Beyond this period, the patent becomes public
      and therefore available to everyone. But the crucial problem is this: when can a
      patent really be used and how to do so as best as possible to guarantee profits
      for both parties involved and thus justify its reason for being? The purpose of
      this work thus is to incite university researchers to think about the real
      usefulness of a patent on the one hand and, on the other hand, to ponder over the
      best way of using, in close cooperation with industry, the fruit of the research
      and the registering of the patent, both financed by public funds. For the latter,
      owing to their nature, demand that there be no wastage and cautious management
      thereof.

PMID- 16890014
TI  - Assessment of left ventricular asynchrony using volume-time curves of 16 segments
      by real-time 3 dimensional echocardiography: comparison with tissue Doppler
      imaging.
AB  - BACKGROUND: Recent technical developments with high-resolution real-time 3
      dimensional echocardiography (RT3DE) facilitate the acquisition of high quality
      images and the analysis of segmental volume-time curves (VTCs). AIMS: To assess
      left ventricular (LV) asynchrony using the VTCs of 16 segments by RT3DE, and to
      evaluate accuracy compared to tissue Doppler imaging (TDI). METHODS: Twenty-three
      heart failure (HF) patients (LVEF: 25+/-6%, age: 60+/-13 years) and 16 normal
      controls underwent TDI and RT3DE. The standard deviation (SD3) of the end
      systolic time reaching minimal systolic volume for the 16 segments on VTCs was
      obtained by RT3DE. The standard deviation (SD2) of the electromechanical coupling
      time for the 8 segments was measured using TDI. RESULTS: SD3 was markedly higher
      in HF patients than in controls (7.7+/-2.5 vs 1.5+/-1.0%, P<0.01) and increased
      as LVEF decreased (r=-0.85, P<0.01). SD2 was also significantly higher in HF
      patients (27.0+/-8.6 vs 12.6+/-5.0 ms, P<0.01) and had a good negative
      correlation with LVEF (r=-0.72, P<0.01). SD3 was well correlated to SD2 (r=0.66,
      P<0.01). CONCLUSIONS: We suggest that analysis of VTCs in 16 segments using RT3DE
      may be a useful alternative to TDI for the evaluation of LV asynchrony.

PMID- 16890016
TI  - The effect of ultrasound stimulation versus bioreactors on neocartilage formation
      in tissue engineering scaffolds seeded with human chondrocytes in vitro.
AB  - Pulsed ultrasound (1 MHz, 67 mW/cm(2) Ispta, and 10 min/day) promoted cell
      proliferation and matrix deposition in low-density 2D ( approximately 6 x
      10(3)cells/cm(2)) as well as 3D ( approximately 4 x 10(6)cells/cm(3)) chondrocyte
      cultures. The beneficial effect of ultrasound on neocartilage formation only last
      28 days, shorter than that of bioreactors.

PMID- 16890017
TI  - Compliance with the Australian national physical activity guidelines for
      children: relationship to overweight status.
AB  - Childhood obesity incidence has increased substantially and it has been argued
      that decreasing physical activity levels, coinciding with an increase in
      sedentary behaviours, are responsible. Australian guidelines were published in
      2004, recommending that children participate in a minimum of 60 min of physical
      activity daily and spend no more than 2h a day using electronic media for
      entertainment. We aimed to compare compliance with these guidelines amongst
      children of differing weight status. The Childhood Injury Prevention Study
      (CHIPS) collected data from a randomly selected sample of Brisbane primary and
      preschool children aged 5-12 years. The following data were available for 518
      participants: age, gender, measured height and weight and estimated time per week
      from a parent-completed 7 days diary in physical activity out of school and
      sedentary leisure activities including television viewing and computer use. Using
      age standardised body mass index estimates, approximately 20% of the cohort were
      overweight. Non-compliance with guidelines was 14.7% for out of school physical
      activity participation, and 30.9% for excess electronic media entertainment use.
      There was a 63% increase in the odds of overweight status amongst children who
      were non-compliant with the electronic entertainment recommendations than those
      who were compliant (adjusted odds ratio=1.63; 95% CI=1.05-2.54). Female gender
      and school level socioeconomic category were also independently associated with
      overweight status. Non-compliance with the minimal physical activity guideline
      increased the odds of being overweight by 28%, however this difference was not
      statistically significant. One in seven children from the Greater Brisbane area
      are at risk for being insufficiently active whilst a third overuse electronic
      media. Given that overuse of electronic entertainment was positively associated
      with childhood obesity, these children should be the target of public health
      campaigns to promote alternative leisure time activities.

PMID- 16890018
TI  - Current prospects for gene therapy of cystic fibrosis.
AB  - Conventional therapy for cystic fibrosis has extended the median survival age,
      but the disease is still fatal. Gene therapy can correct the primary and
      secondary defects associated with cystic fibrosis, but limited extent and
      duration of the corrections as well as concerns about the safety of some current
      delivery systems have prevented gene therapy from being curative. For viral
      vectors, the main challenges are access to target cells and host immunity, which
      prevents efficient re-administration. Masking viral particles from the immune
      system, the use of alternative serotypes, or retargeting have been employed to
      address these issues. Non-viral vectors have dramatically improved over the past
      five years but improvements in efficacy are needed. In lung, naked DNA has been
      inefficient and lipid-based vectors have only achieved efficient gene transfer at
      doses that elicit limiting inflammatory responses. Molecular conjugates or
      polymer-based delivery overcomes some limitations, with good ability to transfect
      non-dividing cells. Improvements of viral and non-viral vectors continue to
      advance the construction of stable, safe and efficacious vectors that can be re
      administered.

PMID- 16890019
TI  - Non-ribosomal factors in ribosome subunit assembly are emerging targets for new
      antibacterial drugs.
AB  - It is becoming increasingly clear that bacterial ribosome assembly is catalyzed
      by a variety of non-ribosomal factors. Newly characterized factors in bacterial
      ribosome biogenesis are broadly conserved and often indispensable proteins that
      can be classified either as chaperones facilitating assembly, or enzymes with
      ribosomal RNA- and ribosomal protein-modifying functions. Accumulating evidence
      indicates that the proteins Era, Obg, YjeQ, YlqF and RimM are chaperones which
      may be crucial to bacterial ribosome assembly, and therefore represent novel
      targets for modern antibacterial drug discovery. Ongoing work aimed at
      understanding ribosome biogenesis is expected to continue to yield additional
      factors crucial to this process, and provide new targets with drug discovery
      potential.

PMID- 16890020
TI  - Drug delivery to the upper small intestine window using gastroretentive
      technologies.
AB  - The bioavailability of drugs with an absorption window in the upper small
      intestine is generally limited with conventional pharmaceutical dosage forms. The
      residence time of such systems and, thus, of their drug release into the stomach
      and upper intestine is often short. To overcome this restriction and to increase
      the bioavailability of these drugs, controlled drug delivery systems with a
      prolonged residence time in the stomach can be used. Approaches to achieving
      prolonged residence times of the devices in the upper part of the
      gastrointestinal tract include the use of bioadhesive, size-increasing, and
      floating drug delivery systems.

PMID- 16890021
TI  - Antibacterial peptides for therapeutic use: obstacles and realistic outlook.
AB  - Cationic antimicrobial peptides are produced by almost all species of life as a
      component of their immediate non-specific defense against infections. The assets
      of these peptides in clinical application include their potential for broad
      spectrum activity, rapid bactericidal activity and low propensity for resistance
      development, whereas possible disadvantages include their high cost, limited
      stability (especially when composed of L-amino acids), and unknown toxicology and
      pharmacokinetics. Initial barriers to their success are being increasingly
      overcome with the development of stable, more cost-effective and potent broad
      spectrum synthetic peptides. Thus, there is hope that they will spawn a new
      generation of antimicrobials with a broad range of topical and systemic
      applications against infections.

PMID- 16890022
TI  - Crossing cellular barriers using dendrimer nanotechnologies.
AB  - Dendrimers represent a class of polymers characterised by their well-defined
      structure, with a high degree of molecular uniformity and low polydispersity.
      They have found a wide-range of pharmaceutical applications; however, more
      recently, they have been shown to function as effective intracellular carriers
      for drugs. In addition, dendrimers have been shown to be capable of bypassing
      efflux transporters. A new generation of dendrimer-based delivery systems will
      enable the efficient transport of drugs across cellular barriers.

PMID- 16890023
TI  - New regulators in adult neurogenesis and their potential role for repair.
AB  - Adult neural stem cells hold great promise for repair because of their unique
      location within the central nervous system, their potential to proliferate and to
      differentiate into all major neural lineages, and their ability to incorporate
      functionally into the existing neuronal circuitry. However, recruitment of these
      cells for repair is hampered by the lack of knowledge about the signals that
      control the generation of a functional neuron from adult neural stem cells. Here,
      we discuss recent findings on the regulatory mechanisms that underlie
      neurogenesis from neural stem cells in the adult hippocampus and the implications
      of these findings for future stem-cell-based repair strategies.

PMID- 16890024
TI  - Severe malaria: lessons learned from the management of critical illness in
      children.
AB  - Two hypotheses have recently been raised to explain the metabolic acidosis
      (increased blood acidity) of severe malaria, and both are relevant to treatment.
      The first suggests that a decreased blood volume (hypovolaemia) has an important
      role in severe malaria; following this, treatment should be based on the current
      standard paediatric management of acidosis in children with features of
      cardiovascular compromise. The second hypothesis contends that acidosis in
      malaria has a metabolic cause and proposes treatment with dichloroacetate. Both
      hypotheses are plausible and are not mutually exclusive. In truth, the risks and
      benefits of either treatment are uncertain, and will remain so until large
      multicentre, randomised controlled trials provide appropriate supportive
      evidence. As both views involve complex physiological rationales, beyond the
      usual scope of this journal, I attempt here to present the largely academic
      aspects of these hypotheses within the practical and contextual aspects of
      childhood severe malaria.

PMID- 16890025
TI  - Understanding the action of INH on a highly INH-resistant Mycobacterium
      tuberculosis strain using Genechips.
AB  - The availability of the complete sequence of Mycobacterium tuberculosis genome
      coupled with microarray technology has enabled a high-throughput approach to the
      pharmacogenomics of this organism. Isoniazid (INH) is a first-line drug for the
      treatment of tuberculosis and the microarray approach has generated new insight
      into the action of INH on a drug-susceptible strain. It has also shown that INH
      does not induce any significant change in gene expression when applied to a
      catalase-negative INH-resistant strain, which is expected because catalase
      activity is required to convert the prodrug INH to its active form. But it has
      yet to be determined how a partially resistant strain responds to INH. In this
      study, we explore the mechanism of INH against a highly INH-resistant strain,
      compare drug-induced gene-expression profiles between resistant and susceptible
      strains, and determine whether or not and how the resistant strain responds to
      INH at low and high concentrations. The global gene-expression profiles of the
      resistant strain in response to INH treatments were obtained using the Affymetrix
      oligonucleotide GeneChips. The results showed that the resistant strain did not
      exhibit the characteristic gene-expression signature of type II fatty acid
      synthase (FAS-II) inhibition when exposed to low-level INH, but it responded with
      that specific pattern under high-level INH, although the response profile was
      somewhat shrunken relative to that for a susceptible strain. We found that INH
      acted on the FAS-II pathway in both resistant and susceptible strains, and little
      evidence suggested that INH might kill resistant bacteria via other mechanisms.
      This suggests that there may be potential benefit of treating INH-resistant
      bacteria with INH at a level that is effective and safe.

PMID- 16890026
TI  - A patient with high risk of gastrointestinal bleeding requiring nonsteroidal anti
      inflammatory drugs.

PMID- 16890027
TI  - Impact of surveillance on survival of patients with initial hepatocellular
      carcinoma: a study from Japan.
AB  - BACKGROUND & AIMS: We investigated trends in the prediagnostic surveillance of
      patients in whom hepatocellular carcinoma (HCC) was diagnosed, and evaluated the
      impact of these trends on early detection of HCC and on patient survival.
      METHODS: We evaluated 1641 patients in whom HCC initially was diagnosed during
      the period of 1968 to 2004. Patients were grouped by the year of diagnosis: 1968
      1980 (n = 151), 1981-1990 (n = 409), 1991-2000 (n = 754), and 2001-2004 (n =
      324). They also were classified according to whether they were in surveillance
      and its context before the diagnosis of HCC: patients undergoing follow-up
      evaluation in our center (group A), those followed up and referred by a primary
      care physician (group B), and those not in surveillance (group C). RESULTS: The
      percentage of patients in groups A and B increased markedly over time. Early
      stage HCC was significantly more prevalent in groups A and B than in group C, and
      the frequency of early stage HCC increased sequentially. The patient survival
      rate was highest in group A, followed by that in groups B and C in that order;
      patient survival improved sequentially. CONCLUSIONS: The percentage of patients
      undergoing in-center surveillance or referred by a primary care physician
      increased, resulting in increased early detection of HCC and improved patient
      survival.

PMID- 16890028
TI  - Tetrandrine concentrations not affecting oxidative phosphorylation protect rat
      liver mitochondria from oxidative stress.
AB  - The effects of tetrandrine (6,6', 7,12-tetramethoxy-2, 2'-dimethyl-berbaman) on
      the mitochondrial function were assessed on oxidative stress, mitochondrial
      permeability transition (MPT), and bioenergetics of rat liver mitochondria. At
      concentrations lower than 100 nmol/mg protein, tetrandrine decreased the hydrogen
      peroxide formation, the extent of lipid peroxidation, the susceptibility to
      Ca(2+)-induced opening of MPT pore, and inhibited the inner membrane anion
      channel activity, not significantly affecting the mitochondrial bioenergetics.
      High tetrandrine concentrations (100-300 nmol/mg protein) stimulated succinate
      dependent state 4 respiration, while some inhibition was observed for state 3 and
      p-trifluoromethoxyphenylhydrazone-uncoupled respirations. The respiratory control
      ratio and the transmembrane potential were depressed but the adenosine
      diphosphate to oxygen (ADP/O) ratio was less affected. A slight increase of the
      inner mitochondrial membrane permeability to H(+) and K(+) by tetrandrine was
      also observed. It was concluded that low concentrations of tetrandrine afford
      protection against liver mitochondria injury promoted by oxidative-stress events,
      such as hydrogen peroxide production, lipid peroxidation, and induction of MPT.
      Conversely, high tetrandrine concentrations revealed toxicological effects
      expressed by interference with mitochondrial bioenergetics, as a consequence of
      some inner membrane permeability to H(+) and K(+) and inhibition of the electron
      flux in the respiratory chain. The direct immediate protective role of
      tetrandrine against mitochondrial oxidative stress may be relevant to clarify the
      mechanisms responsible for its multiple pharmacological actions.

PMID- 16890029
TI  - Method for the determination of blood methotrexate by high performance liquid
      chromatography with online post-column electrochemical oxidation and fluorescence
      detection.
AB  - Methotrexate (MTX) has been widely used at low dose for the treatment of
      different diseases including rheumatoid arthritis. MTX might be present in plasma
      in free form, and in blood cells in methotrexate polyglutamate (MTXPG). A rapid
      and sensitive HPLC method was developed for the determination of plasma MTX
      level, whole-blood MTX level, and whole-blood total MTX (MTX+MTXPG) level. To
      determine plasma MTX level or whole-blood MTX level, a 0.2-ml aliquot of plasma
      or whole blood (after a freeze-thaw cycle to break blood cells) was well mixed
      with 0.8 ml methanol and centrifuged. To determine whole-blood total MTX level, a
      0.1-ml aliquot of whole blood (after a freeze-thaw cycle) was mixed with 80
      microl ascorbic acid (114 mM) and incubated at 37 degrees C for 2h to
      enzymatically convert the MTXPG to MTX. Then 20 microl NaOH solution (0.5M) and
      0.8 ml methanol were added and mixed well. After centrifugation, a 0.5-ml aliquot
      of the supernatant was evaporated to dryness and re-dissolved in 0.2 ml
      hydrochloric acid (10mM). Methylene chloride (0.2 ml) was added and mixed well.
      After centrifugation, the top aqueous layer was injected to HPLC for analysis.
      After the MTX was eluted from the HPLC column, it was electrochemically oxidized
      and detected by a fluorescence detector. Recoveries of spiked MTX at ppb (ng/ml)
      level were between 87.9 and 118% with within-day relative standard deviation less
      than 5.2% and day-to-day relative standard deviation less than 9.8%. The limit of
      detection (LOD) and limit of quantitation (LOQ) of the described method were 1.2
      and 2.6 ng/ml, respectively.

PMID- 16890030
TI  - Optimization and validation of the direct HPLC method for the determination of
      moxifloxacin in plasma.
AB  - Moxifloxacin (1-cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-7-[(4aS,7aS)-octahydro
      6H-pyrrolo-[3,4-b]pyridin-6-yl]-4-oxo-3-quinolinecarboxylic acid hydrochloride)
      is new, fourth generation fluoroquinolone with broaden spectrum of antibacterial
      activity. In the present work simple and rapid RP-HPLC method for the direct
      determination of moxifloxacin in human plasma is described. Separation of
      moxifloxacin from plasma components was achieved on Supelco LC-Hisep shielded
      hydrophobic phase column. The mobile phase consisted of acetonitrile and
      0.25mol/dm(3) Na(3)PO(4) (pH 3) in a volume percent ratio (5:95, v/v) and was
      delivered at a rate of 1mL/min. Fluorescence detection was employed with
      excitation at 290nm and emission at 500nm. Ofloxacin was used as internal
      standard and sodium dodecylsulfate solution was used as a displacing agent.
      Sample preparation was simplified and involved only addition of displacing agent
      and internal standard and dilution with water. The separation conditions were
      optimized by the response surface method in two factor space, i.e. the dependence
      of the retention time on volume percent of acetonitrile and on pH of aqueous
      phase was optimized. The method was fully validated and validation parameters
      were: linearity range 3-1300microg/L; correlation coefficient, 0.99986; mean
      recovery, 92.5%; limit of quantification, 3.0microg/L and limit of detection,
      1.0microg/L. Method was applied for the determination of moxifloxacin in human
      plasma after single or repeated oral doses of 400mg Avelox tablets. The proposed
      method proved to be rapid and accurate and can be successfully used in
      pharmacokinetic studies and routine clinical practice.

PMID- 16890031
TI  - Quantitative analysis of s-adenosylmethionine and s-adenosylhomocysteine in
      neurulation-stage mouse embryos by liquid chromatography tandem mass
      spectrometry.
AB  - The potential importance of the methylation cycle during embryonic development
      necessitates the establishment of methodology to detect alterations in the
      relative abundance of s-adenosylmethionine (SAM) and s-adenosylhomocysteine (SAH)
      in an embryonic experimental system. We have developed a precise and sensitive
      method for measurement of SAM and SAH based on liquid chromatography coupled to
      tandem mass spectrometry (LC-MS/MS) in single neurulation-stage mouse embryos.
      Use of a penta-fluorinated high-performance liquid chromatography (HPLC)
      stationary phase gave enhanced sensitivity due to optimal ionisation in organic
      mobile phase and increased retention time compared to standard reversed-phase
      separation. Calibration curves suitable for the analysis of neurulation-stage
      mouse embryos (SAM 0.02-25.0microM, SAH 0.01-10.0microM) were linear (r(2)>0.997)
      with limits of detection for SAM and SAH of 10 and 2.5nmol/L, respectively.

PMID- 16890033
TI  - Guest editorial: building academic geriatric nursing capacity: the JAHF/AAN
      partnership.

PMID- 16890032
TI  - Effect of disulfide-bond introduction on the activity and stability of the
      extended-spectrum class A beta-lactamase Toho-1.
AB  - The production of class A beta-lactamases is a major cause of clinical resistance
      to beta-lactam antibiotics. Some of class A beta-lactamases are known to have a
      disulfide bridge. Both narrow spectrum and extended spectrum beta-lactamases of
      TEM and the SHV enzymes possess a disulfide bond between Cys77 and Cys123, and
      the enzymes with carbapenem-hydrolyzing activity have a well-conserved disulfide
      bridge between Cys69 and Cys238. We produced A77C/G123C mutant of the extended
      spectrum beta-lactamase Toho-1 in order to introduce a disulfide bond between the
      cysteine residues at positions 77 and 123. The result of 5,5'-dithiobis-2
      nitrobenzoic acid (DTNB) titrations confirmed formation of a new disulfide bridge
      in the mutant. The results of irreversible heat inactivation and circular
      dichroism (CD) melting experiments indicated that the disulfide bridge stabilized
      the enzyme significantly. Though kinetic analysis indicated that the catalytic
      properties of the mutant were quite similar to those of the wild-type enzyme, E.
      coli producing this mutant showed drug resistance significantly higher than E.
      coli producing the wild-type enzyme. We speculate that the stability of the
      enzymes provided by the disulfide bond may explain the wide distribution of TEM
      and SHV derivatives and explain how various mutations can cause broadened
      substrate specificity without loss of stability.

PMID- 16890036
TI  - Mentoring geriatric nurse scientists, educators, clinicians, and leaders in the
      John A. Hartford Foundation Centers for Geriatric Nursing Excellence.

PMID- 16890035
TI  - Overview of the John A. Hartford Foundation building academic geriatric nursing
      capacity initiative.

PMID- 16890037
TI  - Building gerontological nursing research capacity: Research initiatives of the
      John A. Hartford Foundation Centers of Geriatric Nursing Excellence.

PMID- 16890039
TI  - Extending influence in gerontological nursing through partnerships: experiences
      from the John A. Hartford Foundation Centers of Geriatric Nursing Excellence.

PMID- 16890038
TI  - Successful recruiting into geriatric nursing: the experience of the John A.
      Hartford Foundation Centers of Geriatric Nursing Excellence.

PMID- 16890040
TI  - Best practice initiatives in geriatric nursing: experiences from the John A.
      Hartford Foundation Centers of Geriatric Nursing Excellence.

PMID- 16890041
TI  - Innovations in geriatric nursing curricula: experiences from the John A. Hartford
      Foundation Centers of Geriatric Nursing Excellence.

PMID- 16890042
TI  - Developing geriatric nursing leaders via an annual leadership conference.

PMID- 16890043
TI  - Leadership development in the John A. Hartford Foundation Centers of Geriatric
      Nursing Excellence.

PMID- 16890044
TI  - Influencing health policy for older adults: initiatives by the John A. Hartford
      Centers of Geriatric Nursing Excellence.

PMID- 16890045
TI  - Outcomes and lessons learned from the John A. Hartford Foundation Building
      Academic Geriatric Nursing Capacity Initiative Centers of Geriatric Nursing
      Excellence.

PMID- 16890064
TI  - Morphine/ondansetron PCA for postoperative pain, nausea, and vomiting after skull
      base surgery.
AB  - OBJECTIVE: Patients who underwent skull base procedures have been noted to
      experience appreciable pain. This study examines pain after surgery and the
      effectiveness of patient controlled analgesia (PCA) with combination morphine
      ondansetron for analgesia and control of emesis. STUDY DESIGN AND SETTING: A
      total of 120 skull base surgery patients were randomized to receive placebo,
      morphine, or morphine ondansetron. Demographic and intraoperative variables were
      recorded along with pain, nausea, vomiting, and rescue analgesics. Total PCA use,
      hospital stay, satisfaction, and cost were also compared. RESULTS:
      Demographically the groups were similar. Pain was elevated with placebo PCA, and
      this group averaged twice as many analgesic rescues. Total usage time was lower
      with placebo PCA. Morphine ondansetron PCA had the lowest pain score with highest
      satisfaction. Nausea and vomiting was similar but female patients had more
      vomiting regardless of PCA group. CONCLUSIONS AND SIGNIFICANCE: The use of
      morphine PCA reduced pain and did not appreciably increase nausea or vomiting.
      The addition of ondansetron produced no real benefit and its PCA use cannot be
      justified. EBM RATING: A-1b.

PMID- 16890065
TI  - Treatment of pain after head and neck surgeries: control of acute pain after head
      and neck oncological surgeries.
AB  - OBJECTIVE: To devise an effective postoperative analgesic protocol. STUDY DESIGN
      AND SETTING: Two consecutive groups participated in this study. In the first
      group (n = 100), the pain-control management was pro re nata (PRN). In the second
      group, (n = 109) we tailored a procedure-specific pain-control protocol for each
      patient according to the level of pain recorded in the first group. These
      patients were treated with analgesics given at predetermined hours. Pain was
      evaluated by using a verbal scale of 1 to 10. RESULTS: In the first group, a
      significant reduction in the level of pain was monitored 1 hour after PRN drug
      administration; however, patients reported the return of pain several hours
      later, after the drug effect subsided. Overall, the patients suffered a
      substantial level of pain during the entire postoperative period. In the second
      group, significant reduction in the level of pain was recorded throughout the
      hospitalization. CONCLUSION: The PRN protocol is not adequate for management of
      pain after head and neck surgeries. SIGNIFICANCE: We can substantially reduce our
      patients' postoperative pain by adopting a procedure-specific analgesic regimen
      instead of a PRN regimen. EBM RATING: B-3b.

PMID- 16890067
TI  - Factors influencing publication of abstracts presented at the AAO-HNS Annual
      Meeting.
AB  - OBJECTIVE: To examine abstracts presented at the American Academy of
      Otolaryngology-Head and Neck Surgery (AAO-HNS) Annual Meeting and to identify
      factors associated with publication success. STUDY DESIGN AND SETTING: All
      abstracts published in the August 1999 official program issue of the AAO-HNS
      Journal were examined. MEDLINE searches were performed to assess publication
      success. Multivariate analysis was performed to identify factors related to
      successful publication. RESULTS: We identified 473 abstracts, of which 260 (55%)
      were poster presentations. Median publication time was 16 months, with a
      publication rate of 50%. Multivariate analysis revealed oral presentation,
      statistical analysis, and number of authors to be the most significant predictive
      factors of publication success (odds ratios of 2.2, 1.9, and 1.2 respectively).
      Level of evidence did not correlate with publication success, even when case
      reports (n = 70) were excluded from the analysis. Publication rates in other
      disciplines ranged from 25% to 68%, with a mean of 47%. CONCLUSIONS: The rate of
      publication from the AAO-HNS Annual Meeting is similar to other disciplines. Oral
      presentations with inferential statistics in the abstract were most likely to be
      published. Conversely, level of evidence and direction of study inquiry were not
      significant predictors, suggesting that research design is a less important
      determinant of publication success. SIGNIFICANCE: Our investigation is one of the
      first to critically analyze the factors in presentations at annual meetings that
      predict successful publication.

PMID- 16890066
TI  - Unique challenges of obtaining regulatory approval for a multicenter protocol to
      study the genetics of RRP and suggested remedies.
AB  - OBJECTIVE: Investigations that seek to generalize findings or to understand
      uncommon diseases must be conducted at multiple centers. This study describes the
      process of obtaining regulatory approval for a minimal risk genetic study in a
      multi-center setting as undertaken by the Recurrent Respiratory Papillomatosis
      (RRP) Task Force. STUDY DESIGN AND SETTING: Sequential cohort of American
      children's hospitals. A single protocol was submitted to each Institutional
      Review Board (IRB). RESULTS: Documentation was prepared for 14 IRBs over 2.5
      years. The median time between enlistment and approval at the first 8 sites was
      15 months. Institutions varied considerably in their requirements and in the
      issues that were raised. Protocols were submitted sequentially and accumulated
      experience was used in the preparation of applications to subsequent IRBs.
      Nevertheless, there was no correlation between the accumulated experience and the
      number of issues that were raised. CONCLUSION: Despite uniform federal standards,
      all local IRBs required unique and individualized submissions. For multicenter
      studies, investigators should seriously consider the establishment of cooperative
      authorization agreements. On a simpler level, a standardized format for
      applications needs to be adopted nationwide. EBM RATING: B-3b.

PMID- 16890068
TI  - Frozen versus fresh reconstituted botox for laryngeal dystonia.
AB  - OBJECTIVES: To compare the efficacy and side effects of frozen versus fresh
      reconstituted botulinum toxin type A (BTX-A) in the treatment of laryngeal
      dystonia. STUDY DESIGN AND SETTING: Prospective open-label crossover study; 43
      adult patients with adductor spasmodic dysphonia were randomly treated with fresh
      or refrozen reconstituted BTX-A at a private voice center. Treatment outcomes
      were assessed by duration of action and self-rated satisfaction (7 point Likert
      scale). Side effects of breathiness and dysphagia for liquids were assessed as
      well. RESULTS: There was no statistically significant difference in the duration
      of action (mean, 16.2 +/- 8.5 vs 16.0 +/- 7.6 weeks) and self-rated satisfaction
      of the treatment (median, 6.0 vs 6.0 points). The side effects were similar for
      both BTX-A injection types. In addition, there were no instances of infection for
      refrozen injections. CONCLUSIONS: BTX-A may be safely used after being
      reconstituted and frozen or refrozen without a significant loss of effectiveness
      or additional side effects. In our experience, the period of freezing was on 2
      occasions for up to 8 weeks. SIGNIFICANCE: Refrozen BTX-A may be a cost-effective
      use of an expensive drug. EBM RATING: B-2b.

PMID- 16890070
TI  - Can a fluoroscopic estimation of pharyngeal constriction predict aspiration?
AB  - BACKGROUND: The pharyngeal constriction ratio (PCR) is a ratio of pharyngeal area
      measured in lateral fluoroscopic view at the point of maximum pharyngeal
      constriction during the swallow to the pharyngeal area measured with the bolus
      held in the oral cavity. We hypothesize that the PCR may represent a surrogate
      measure of pharyngeal strength. OBJECTIVE: To investigate the relationship
      between the PCR and aspiration. STUDY DESIGN AND SETTING: Data from a
      computerized clinical database of individuals undergoing a videofluoroscopic
      swallow evaluation at a tertiary academic swallowing center was acquired.
      RESULTS: Two hundred sixty videofluoroscopic studies were abstracted. The mean
      PCR was 0.32 (+/- 0.02) for individuals who aspirated and 0.20 (+/- 0.02) for
      individuals who did not (P < 0.001). In a multiple logistic regression analysis,
      the PCR was significantly associated with the prevalence of aspiration (P <
      0.01). Individuals with a PCR greater than 0.25 were 3 times more likely to
      aspirate (95% CI = 1.7, 5.1). CONCLUSIONS: The pharyngeal constriction ratio is
      associated with the presence of aspiration on fluoroscopy. Before the PCR can be
      used as a surrogate measure of pharyngeal constriction, correlation with
      pharyngeal manometry will be necessary. SIGNIFICANCE: The pharyngeal constriction
      ratio is associated with the presence of aspiration on fluoroscopy. EBM RATING: B
      3b.

PMID- 16890069
TI  - High efficiency gene delivery into laryngeal muscle with bidirectional
      electroporation.
AB  - OBJECTIVE: The impact of polarity change on the efficiency of in vivo
      electroporative (EP) gene transfection was assessed in rat laryngeal muscle.
      STUDY DESIGN AND SETTING: High (HV) and low field voltage (LV) were combined with
      polarity changes to determine transfection in 5 different conditions: 1) without
      EP (EP[-]), 2) HV+LV (HL), 3) HV+LV followed by HV+LV with no change in polarity
      (HLHL unidirectional), 4) HV+LV followed by HV+LV with opposite polarity (HLHL
      bidirectional), 5) HV+LV followed by LV with opposite polarity (HLL
      bidirectional). RESULTS: HLL bidirectional sequence showed the best result with
      less interindividual variability and extended expression period. With the
      exception of repeated high voltage sequences, EP parameters were not likely to
      induce cell injury or inflammation. CONCLUSION: HLL bidirectional electroporative
      gene delivery produces high transfection rates with limited tissue trauma.
      SIGNIFICANCE: Bidirectional EP provides a safe and highly efficient method for
      therapeutic gene delivery into skeletal muscle.

PMID- 16890071
TI  - Long-term results of cricopharyngeal myotomy in oculopharyngeal muscular
      dystrophy.
AB  - OBJECTIVE: To analyze long-term results of extramucosal cricopharyngeal myotomy
      in oculopharyngeal muscular dystrophy. STUDY DESIGN: The preoperative and
      postoperative evaluations including symptoms, type of feeding, weight, and
      functional examinations were retrospectively evaluated in 39 patients. Results
      were defined postoperatively as successful, partial, or failed. SETTING:
      University hospital. RESULTS: In the short term, 25 patients showed a complete
      remission of symptoms, 10 showed a marked improvement, and 4 exhibited no
      improvement at all (success rate of 90%). Long-term evaluation during a mean
      follow-up of 4 years showed that of the 35 improved patients, 12 exhibited a
      recurrence of dysphagia (mean time of 39 months). In 3 of these 12 patients, a
      revision transmucosal endoscopic cricopharyngeal myotomy was performed with a
      successful outcome in 2. Of the 4 patients who initially showed no improvement, 1
      was improved by transmucosal myotomy. CONCLUSION: Extramucosal cricopharyngeal
      myotomy improves dysphagia in oculopharyngeal muscular dystrophy patients during
      the first few years but one third of the patients exhibited a recurrence of
      symptoms within 3 years. Revision by transmucosal endoscopic myotomy may be
      performed. EBM RATING: C-4.

PMID- 16890072
TI  - Tracheobronchial foreign body aspiration: a continuing challenge.
AB  - OBJECTIVE: The aim was to present the features and outcomes for 140 cases of
      foreign body aspiration and to discuss specific problems and new management
      recommendations. STUDY DESIGN AND SETTING: Records were retrospectively reviewed
      and the following data were recorded for each patient: age, sex, symptoms,
      duration of symptoms, findings on physical examination and chest radiography,
      location and type of foreign body, complications related to aspiration itself or
      to extraction, and outcome. RESULTS: Seventy-eight (55.7%) patients presented
      within 24 hours of aspiration. The most common symptoms and findings were cough,
      dyspnea-stridor, decreased breath sounds, radiopaque foreign body, air trapping,
      and atelectasis. All 140 patients underwent rigid bronchoscopy, and 110 had the
      foreign material extracted via the scope. No foreign body was detected
      bronchoscopically in 25 cases. In the other 5 cases, the material was visualized
      but could not be removed via the scope, and 3 of these patients required
      thoracotomy for removal. Eleven patients developed morbidity after bronchoscopy.
      CONCLUSIONS: History suggestive of foreign body aspiration is a definite
      indication for bronchoscopy, and bronchoscopic extraction should only be
      performed by experts. Each case tends to present different challenges, and
      endotracheal intubation and tracheotomy may be required.

PMID- 16890073
TI  - Four suture tip rhinoplasty: a powerful tool for controlling tip dynamics.
AB  - OBJECTIVE: To evaluate the short-term effectiveness of using a 4-suture technique
      to control nasal tip dynamics. The 4 sutures include a medial crural suture,
      bilateral intradomal sutures, and an interdomal suture. STUDY DESIGN AND SETTING:
      Retrospective photograph analysis of preoperative and postoperative photographs
      of 77 patients with respect to 7 dynamic variables: supratip break, projection,
      rotation, tip shape, tip definition, tip symmetry, and the presence of a double
      columellar break. RESULTS: Seventy-four patients underwent primary rhinoplasty
      and had an overall average score of 5.2 on a -7 to +7 scale, with a mean follow
      up period of 3.8 months. The 3 patients undergoing revision rhinoplasty had an
      overall average score of 5.0 and a mean follow-up of 8.7 months. CONCLUSION: The
      4-suture technique worked best with respect to projection and tip symmetry,
      although the technique proved to be an effective tool overall in controlling all
      7 variables mentioned above. EBM RATING: C-4.

PMID- 16890074
TI  - Intradermal positivity after negative prick testing for inhalants.
AB  - OBJECTIVE: Examine the incidence of positive intradermal tests after a negative
      skin prick test for 24 inhalant antigens. STUDY DESIGN AND SETTING: Retrospective
      study. Charts from patients who underwent modified quantitative testing (MQT)
      over a 3-year period were reviewed. Patients were initially tested with Multi
      Test II. Subjects with negative wheals to a specific allergen were then tested
      with a 1:500 weight:volume intradermal injection of that allergen. RESULTS: One
      hundred thirty-three patients underwent MQT for 24 antigens. Allergens with the
      highest incidence of positive intradermal wheals after negative prick testing
      were Dermatophagoides pteronyssinus and Dermatophagoides farinae at 26.67%.
      Allergens with elevated incidence of positive intradermals included fusarium,
      cockroach, cocklebur, rough marsh elder, and ragweed, all with incidences of 16%
      to 19%. CONCLUSION: Positive intradermal responses after negative prick testing
      occur commonly. Future study is needed to determine the generalizability and
      clinical significance of these findings. EBM RATING: C-4.

PMID- 16890075
TI  - Nasal polyp diseases in allergic and nonallergic patients and steroid therapy.
AB  - OBJECTIVE: To investigate widespread disease causes, cellular-structural
      differences, and steroid response of nasal polyps (NPs). METHOD: Study group
      consisted of NPs, allergic-NPs, NPs with steroid therapy (ST), antrochoanal polyp
      (ACP), and controls. We investigated stromal eosinophil, mast cell, CD4+ and CD8+
      cell counts and presence of squamous metaplasia, Ki-67 expression,
      intraepithelial eosinophils-mast cells, epithelial damage, edema, fibrosis,
      hyalinization, polymorphonuclear leukocyte, and glandular hyperplasia. RESULTS:
      In allergic-NPs, intraepithelial eosinophils and epithelial damage CD4+ were
      significantly higher than NPs and also, eosinophils, mast cells, intraepithelial
      eosinophils, and epithelial damage were significantly higher than ACP. Only
      stromal eosinophilic infiltration was significantly higher in NPs than ACP. There
      was significant increased glandular hyperplasia and decreased intraepithelial
      eosinophils, mast cells, CD4+ cells, squamous metaplasia, and epithelial damage
      with ST in allergic-NPs. There were no significant differences with ST in NPs.
      CONCLUSION: NPs in allergic and nonallergic patients may differ in their
      histology and in their histologic responses to ST. EBM RATING: B-3b.

PMID- 16890076
TI  - DQA1 and DQB1 association and nasal polyposis.
AB  - OBJECTIVE: The aim of this study was to determine the contribution of the human
      major histocompatibility complex (HLA)-DQA1, -DQB1, and TNFalpha genes with
      simple nasal polyposis. STUDY DESIGN AND SETTING: A comparative case-control
      study with 31 patients and 151 controls was performed. HLA-DQA1, -DQB1, and
      TNFalpha -238 promoter position loci were typed by polymerase chain reaction
      (PCR) and sequence specific oligonucleotide probes (SSOPs). TNFalpha -308
      promoter position was determined by PCR and digestion with NcoI restriction
      enzyme. RESULTS: The allele HLA-DQA1*0201 (P(c) = 0.019) had an etiologic
      fraction (EF) of 17%, whereas 13% EF was found for the haplotype HLA-DQA1*0201
      DQB1*0201 (P = 0.016). Analysis of -DQB1 and TNFalpha promoter did not show
      significant differences between cases and controls. CONCLUSIONS: HLA-DQA1*0201
      DQB1*0201 haplotype is involved in susceptibility, conferring 5.53 times more
      risk of developing this disease. EBM RATING: B-2b.

PMID- 16890077
TI  - Management of recurrent sinus disease in children with cystic fibrosis: a
      combined approach.
AB  - OBJECTIVE: To determine whether a combined approach (CA) consisting of functional
      endoscopic sinus surgery (FESS), Caldwell-Luc operation, and medial maxillectomy
      is beneficial for children with cystic fibrosis (CF) with refractory sinonasal
      disease previously treated with endoscopic procedures alone. STUDY DESIGN:
      Retrospective review and comparison of outcomes of CA and FESS alone for each CF
      patient. OUTCOMES MEASURED: sinonasal symptoms, endoscopic findings, number of
      hospitalizations, antibiotic courses, and forced expiratory volume in 1 second
      (FEV1). SETTING: Referral hospital. RESULTS: Fifteen children underwent CA
      between 1996 and 2000 (7 males, 8 females; 13.8 years mean age; 42 months average
      follow-up period). Significant decrease in number of hospitalizations and
      intravenous antibiotic courses, with increased mean FEV1 (from 70.2% preoperation
      to 89.3% postoperation, P < 0.0001) were found. Marked clinical improvement
      persisted for several years. CONCLUSION: Applying the CA after multiple failed
      endoscopic procedures in CF patients reduced morbidity and resulted in successful
      management of sinonasal disease. CA is suggested after multiple failed endoscopic
      procedures. Further studies of CA as a first-line procedure for difficult sinus
      cases in children with CF is recommended. EBM RATING: C-4.

PMID- 16890078
TI  - Gastroesophageal reflux and laryngopharyngeal reflux in patients with sleep
      disordered breathing.
AB  - OBJECTIVE: To assess the relationship of gastroesophageal reflux (GER) and
      laryngopharyngeal reflux (LPR) with obstructive sleep apnea (OSA). PATIENTS AND
      METHODS: Thirty-seven sleep-disordered breathing (SDB) patients underwent
      polysomnography (PSG) and dual-channel pH probe testing. LPR was defined as
      greater than 6.9 proximal reflux episodes or reflux area index (RAI) greater than
      6.3. GER was defined as greater than 4% of time below pH 4.0. RESULTS: OSA was
      present in 28 patients. Twenty-three patients had LPR (66.7% of snorers, 60.7% of
      OSA patients). Twenty-one patients had GER (33.3% of snorers, 64.3% of OSA
      patients). Body mass index (BMI) correlated positively with respiratory
      disturbance index (RDI) (r = 0.67, P < 0.001). BMI did not correlate with pH
      probe parameters. OSA presence/severity did not correlate with LPR or GER. Supine
      LPR and GER events did not correlate with OSA presence/severity. CONCLUSION:
      Gastric acid reflux is prevalent in SDB patients. Direct correlations between
      reflux and PSG parameters were not identified. EBM RATING: B-2b.

PMID- 16890079
TI  - Palatal and tongue base surgery for surgical treatment of obstructive sleep
      apnea: a prospective study.
AB  - OBJECTIVE: To assess the effect of concurrent uvulopalatopharyngoplasty (UPPP)
      and hypopharyngeal procedures in obstructive sleep apnea (OSA) patients with
      diffuse airway narrowing. STUDY DESIGN AND SETTING: Forty-eight patients were
      treated surgically by a single surgeon in private practice over 2 years.
      Symptoms, Epworth score, and polysomnographic outcome were assessed
      preoperatively and postoperatively. The Friedman staging system was applied. UPPP
      with genioglossus advancement, hyoid suspension, or radiofrequency treatment was
      carried out. RESULTS: In 37 patients with complete data, the average apnea
      hypopnea index (AHI) was reduced from 46.5 +/- 24.8 to 14.9 +/- 16.8. The Epworth
      score was reduced from 12.1 +/- 4.9 to 6.7 +/- 3.7. Most patients reported
      improved sleep quality, alertness, memory, concentration, and mood. CONCLUSION:
      Successful outcome, defined by symptom and AHI reduction, was achieved with
      multilevel surgery for most patients with advanced Friedman stages 2 and 3.
      SIGNIFICANCE: Multilevel surgery seems effective in treating severe OSA patients
      with diffuse airway narrowing. EBM RATING: C-4.

PMID- 16890080
TI  - A comparison of polysomnography and the SleepStrip in the diagnosis of OSA.
AB  - OBJECTIVE: To investigate the role of a portable screening device (SleepStrip) in
      the diagnosis of obstructive sleep apnea (OSA). METHODS AND MATERIALS:
      Prospective, nonrandomized double-blinded single cohort study at an academic
      health center. Patients with suspected OSA scheduled for an attended overnight
      Level I polysomnogram (PSG) and who consented to participate in the study wore
      the SleepStrip device at home the night after the PSG. The apnea-hypopnea index
      (AHI) determined by PSG was compared with the results of the SleepStrip
      recording. RESULTS: Thirty-seven patients with a mean age of 52.1 +/- 12.2 years
      and mean body mass index of 35.7 +/- 5.2 participated in the study. The overall
      agreement between the AHI and the SleepStrip results using Cohen's Kappa value
      was 0.139 (P = 0.19). The sensitivity and specificity of the SleepStrip for
      diagnosing severe OSA when the AHI was >40 were 33.3% and 95% (P = 0.05). When
      the AHI was >25, the SleepStrip sensitivity and specificity were 43.8% and 81.3%
      (P = 0.26). The sensitivity and specificity of the SleepStrip for diagnosing OSA
      in patients with an AHI >15 were 54.6% and 70%, respectively (P = 0.26).
      CONCLUSION: The SleepStrip has a low correlation with the AHI as measured by PSG.
      Further studies are needed before this device can be recommended as a screening
      tool for the diagnosis of OSA. EBM RATING: B-2b.

PMID- 16890081
TI  - Acoustic parameters of snoring sound to assess the effectiveness of sleep
      nasendoscopy in predicting surgical outcome.
AB  - OBJECTIVE: To assess the effectiveness of two grading systems used to predict
      surgical outcome in nonapneic snorers. STUDY DESIGN: A prospective observational
      study. Prior to undergoing palatal surgery, 20 patients completed a sleep
      nasendoscopic examination involving sequential steady-state sedation with
      intravenous propofol. Using a combination of acoustic parameters of snoring sound
      as an objective outcome measurement, and the answers to a specifically designed
      questionnaire as a subjective outcome measurement, the effectiveness of each
      grading system in predicting surgical outcome was examined. RESULTS: Depending on
      the outcome measurement used, sensitivity in predicting success of surgery for
      snoring varied from 16.7% to 50.0% and specificity from 38.5% to 62.5% for the
      Pringle and Croft system, while sensitivity varied from 91.7% to 100% and
      specificity from 30.8% to 31.5% for the Camilleri system. CONCLUSION: Sleep
      nasendoscopy using these classifications cannot be recommended as a reliable
      predictor of surgical outcome in nonapneic snorers. EBM RATING: C-4.

PMID- 16890082
TI  - Efficacy of steroid injection on idiopathic sudden sensorineural hearing loss.
AB  - OBJECTIVE: To evaluate the effectiveness of transtympanic steroid injection on
      patients with idiopathic sudden sensorineural hearing loss (ISSNHL) compared with
      patients who receive oral steroids alone. STUDY DESIGN: Retrospective chart
      review. METHODS: Patients with a history of ISSNHL and failed oral steroid
      therapy were included. Audiograms were performed and patients were included if
      SNHL of more than 20 dB occurred over less than 72 hours. Patients who received
      transtympanic steroid injection were compared with those who received oral
      steroids alone. RESULTS: Sixty-one patients met inclusion criteria and were
      included in the study. The number of patients with improvement in pure tone
      average in the injection group was 9 (30%) compared with 5 (17%) in the oral
      group. Twelve (38.7%) of the injected patients did have improvement in speech
      discrimination scores of greater than 15% compared with only 3 (10%) in the oral
      steroid group. CONCLUSION: Our study revealed that patients with ISSNHL who have
      failed oral steroid therapy obtain better hearing results with transtympanic
      steroids in comparison to oral steroids. EBM RATING: B-3b.

PMID- 16890083
TI  - Alloplastic bone cements in otologic surgery: long-term follow-up and lessons
      learned.
AB  - OBJECTIVE: Otolaryngologists are often confronted with structural defects in the
      tegmen, scutum, or external auditory canal (EAC). Carbonated calcium phosphate
      (CCP) bone cements offer an alternative way of managing these defects. STUDY
      DESIGN AND SETTING: Retrospective review in an academic otology practice. The
      technical feasibility of these techniques described as well as the wound healing
      and structural integrity results. RESULTS: CCP bone cement was used to
      reconstruct defects of the tegmen or EAC in 22 patients. The material was used to
      repair the EAC in 19 of these patients, including complete EAC reconstruction in
      4 patients, and tegmen defects only in 3 cases. CONCLUSION: The surgical
      technique is not technically difficult and the alloplastic material is hard
      within minutes of application. Twenty patients have been followed for over 1 year
      with an average follow-up period of 3.8 years. Failure, defined as infection or
      explantation, occurred in 4 patients followed over 3 years. There was a
      difference in outcomes for pediatric cases. EBM RATING: C-4.

PMID- 16890084
TI  - The application of vestibular-evoked myogenic potentials in otoneurosurgery.
AB  - OBJECTIVE: To evaluate the applicability of vestibular-evoked myogenic potentials
      (VEMPs) in the diagnostics, intraoperative monitoring, and postoperative follow
      up of patients in otoneurosurgery. STUDY DESIGN: A prospective study of patients
      who underwent either cochlear implantation (CI, n = 18) or were diagnosed with an
      acoustic neuroma (AN, n = 9) or with neuro(micro)vascular compression of the
      VIIIth nerve (NVC, n = 27) in the period 2002 to 2004. The follow-up was 1 year
      for all patients. SETTING: A tertiary-referral unit. RESULTS: VEMPs could be
      recorded in 64% of all patients before CI and in 22% after surgery. The patients
      with AN had normal VEMPs in 22% of all cases when first diagnosed. Normal VEMPs
      were found in 37% of those patients with NVC. From the 5 AN patients who had to
      be operated, only 1 had intact VEMPs after surgery. In contrast, after
      microvascular decompression all patients (4) had normal VEMPs. CONCLUSIONS: VEMPs
      are helpful in diagnosing patients with vertigo to better identify saccular
      defects. They are highly sensitive in the early diagnosis of retrocochlear
      lesions. SIGNIFICANCE: VEMPs can help to reliably identify patients with a
      retrocochlerar lesion at an early stage and can be used in intraoperative,
      neurophysiological monitoring. EBM RATING: C-4.

PMID- 16890085
TI  - Topical otic antibiotics: clinical cochlear ototoxicity and cost consideration.
AB  - OBJECTIVE: Determine the incidence of clinical cochlear ototoxicity in routine
      use of Cortisporin after ventilation tube placement. Cost differential between
      use of Cortisporin and fluoroquinolone agents was evaluated. METHODS: A
      retrospective review of 500 patients was performed. Cortisporin otic suspension
      was used for 5 days following ventilation tube insertion. RESULTS: Testing
      following surgery indicated a sensorineural hearing loss (SNHL) in 19 (2.1%)
      ears. The SNHL existed prior to the surgery and there was no deterioration in the
      hearing postoperatively. The total cost for our study group who used Cortisporin
      was $15,500. If Floxin had been prescribed the cost would have been $45,000. Had
      Ciprodex been prescribed, the cost would have been $49,500. CONCLUSION: Our study
      demonstrates no clinical cochlear ototoxicity in children who received
      Cortisporin following ventilation tube placement. The cost differential for
      prescribing fluoroquinolone drops is significant. EBM RATING: C-4.

PMID- 16890086
TI  - Minimal incision for open thyroidectomy.
AB  - OBJECTIVES: To establish the incision length for thyroid surgery that optimizes
      access and cosmesis. STUDY DESIGN AND SETTING: Prospective study from January
      2003 to June 2004. All thyroidectomies were included. Exclusion criteria were
      concomitant neck dissections, previous surgery, and those performed
      endoscopically. The first 40 cases were attempted through a 5 cm incision and the
      second 40 through a 4 cm incision. METHODS: In both groups, the size of the
      incision was compared with the thyroid's weight and histology. RESULTS: Two
      subtotal, 22 total, and 56 hemithyroidectomies were performed. In the first
      group, median gland weight was 39.5 gm and 62.5% of these were removed through a
      5 cm incision. In the second group, median gland weight was 34 gm and 75% were
      removed through a 4 cm incision. CONCLUSION: A 4 cm incision provides adequate
      access for the majority of thyroidectomies in our cohort. SIGNIFICANCE: The
      minimal incision thyroidectomy is a useful addition to the thyroid surgeon's
      armamentarium. EBM RATING: B-3b.

PMID- 16890087
TI  - Reliable surgical landmarks for the identification of the recurrent laryngeal
      nerve.
AB  - OBJECTIVE: To obtain reliable landmarks for identification of the recurrent
      laryngeal nerve in human larynges. STUDY DESIGN AND SETTING: This is a
      prospective study, analyzing the laryngeal anatomic features. Structures easily
      palpable on the thyroid and cricoid cartilage (ie, the most prominent portion of
      the inferior cornu of the thyroid cartilage [IC], the inferior tubercle of the
      thyroid cartilage [ITT] and the most anterior portion of the arch of the cricoid
      cartilage [AC]) were accepted as landmarks and the distances of these structures
      to the entrance point of the RLN on the medial aspect of the inferior pharyngeal
      constrictor muscle (cross point [CP]) were measured in 65 adult autopsies.
      RESULTS: When a straight line is drawn 11 to 12 millimeters (mm) from the IC, 22
      to 24 mm from the ITT, and 26 to 28 mm from the AC, the point at which they
      intersect indicates the point at which the RLN enters the medial side of the
      inferior pharyngeal constrictor muscle (ICM) and is easy to locate at this point.
      All of the RLN were seen to lie posterolateral to the Berry ligament. Thirty
      eight of 65 cases possessed extralaryngeal bifurcation of the RLN. CONCLUSION:
      With such constant mathematic values, these 3 landmarks are reliable markers for
      identification of RLN. This study is important in the fact that it states
      constant mathematic values regarding surgical landmarks used to expose the RLN.

PMID- 16890088
TI  - Aggressive maxillofacial disassembly in skull base surgery.
AB  - OBJECTIVE: To review our favorable experience with maxillofacial disassembly for
      exposure and resection of tumors of the skull base. PATIENTS AND METHODS: This is
      a retrospective review of 31 patients from 1997 to 2005 treated by maxillofacial
      disassembly and includes 22 patients with midface disassembly and 9 patients with
      mandible with or without midface disassembly. RESULTS: Follow-up ranges from 2
      weeks to 7 years: 23 (74.2%) of 31 patients are alive and disease free; 3
      patients are alive with disease; 3 patients have died of distant metastasis.
      There were 14 complications in 12 (38.7%) patients; 13 of 14 complications were
      minor. One major complication (cardiovascular accident) resulted in the single
      postoperative mortality in this series. CONCLUSION: Our technique of
      maxillofacial disassembly allows for tailored exposure of all regions of the
      anterolateral skull base with acceptable perioperative morbidity in appropriately
      selected patients. EBM RATING: C-4.

PMID- 16890089
TI  - Primary head and neck Langerhans cell histiocytosis in children.
AB  - OBJECTIVE: To evaluate the experience of a tertiary care children's hospital in
      the diagnosis, treatment, and long-term outcomes of patients with primary head
      and neck Langerhans' cell histiocytosis. STUDY DESIGN AND SETTING: A
      retrospective study of patients who presented with Langerhans' cell histiocytosis
      that primarily affected head and neck sites between January 1, 1986, and December
      31, 2004, at Children's Mercy Hospital. RESULTS: Twenty-two patients were
      diagnosed and treated for LCH at our hospital during this time period. Seventeen
      (77%) patients had head and neck involvement; 14 (64%) of these patients had
      primary head and neck LCH. Lesions of the head and neck are complicated and
      involve multiple structures including the calvarium and skull base. Overall
      outcomes were good with 10 of 14 patients without disease at time of last follow
      up. Recurrence is common and involved 50% of our patients. CONCLUSIONS:
      Langerhans' cell histiocytosis commonly affects the head and neck. These lesions
      are complex and require prudent evaluation and treatment. Due to the complex
      nature of head and neck lesions, primary chemotherapy is the treatment of choice.
      SIGNIFICANCE: Because of the frequent head and neck involvement of this disease,
      otolaryngologists need to be familiar with its presentation, work-up, and
      treatment. EBM RATING: C-4.

PMID- 16890090
TI  - Pediatric partial cricotracheal resection: a new technique for the posterior
      cricoid anastomosis.
AB  - OBJECTIVE: Partial cricotracheal resection has become a more popular procedure in
      the pediatric population as a treatment for severe subglottic stenosis. We
      describe a new technique for the posterior cricoid anastomosis. STUDY DESIGN AND
      SETTING: This is a case series of 4 pediatric patients with a Myer-Cotton grade
      III or IV subglottic stensosis. SETTING: Tertiary care hospital with a pediatric
      intensive care unit. RESULTS: All 4 patients were decannulated and there were no
      observed complications to include posterior mucosal dehiscence and/or recurrent
      laryngeal nerve injury. CONCLUSIONS: Placing sutures through the cricoid
      cartilage is technically less difficult than previously described techniques for
      treating subglottic stenosis near the undersurface of the true vocal folds and
      affords a more stable posterior mucosal suture line. SIGNIFICANCE: This technique
      provides a surgical means to treat high subglottic stenosis that closely
      approximates the true vocal folds by enabling a stable posterior mucosa to mucosa
      apposition. EBM RATING: Grade C-4.

PMID- 16890091
TI  - Bipolar radiofrequency for adenoidectomy.

PMID- 16890092
TI  - Venous malformation of the sternomastoid muscle.

PMID- 16890093
TI  - Visual loss in a child due to allergic fungal sinusitis of the sphenoid.

PMID- 16890094
TI  - Fibromyxoma of the maxilla.

PMID- 16890095
TI  - Unilateral submandibular gland aplasia: an isolated phenomenon of early fetal
      development.

PMID- 16890096
TI  - Nasal septal abscess.

PMID- 16890097
TI  - Reply to: Correlation between middle turbinate and ipsilateral ethmoid
      histopathology in chronic rhinosinusitis.

PMID- 16890099
TI  - Malpractice in geriatrics: are we surviving?

PMID- 16890100
TI  - Medication overuse and misuse.

PMID- 16890102
TI  - Libraries of life: using life history books with depressed care home residents.
AB  - Depression is a common, and often undetected, psychiatric disorder in geriatric
      care home residents. Reminiscence, an independent nursing therapy used by a
      variety of health and social care professionals, can prevent or reduce
      depression. This practice development project explored the use of reminiscence
      life history books as an interpersonal therapeutic tool with 3 depressed care
      home residents living in residential care and skilled nursing facilities. The
      process of choosing to produce a book, assessment of capabilities, and methods of
      construction are described using 3 illustrative case studies. Three themes
      emerged: reviewing the past, accepting the present, and dreaming of an
      alternative future. This project demonstrated that life history books, tailored
      to individual needs and abilities, can facilitate reminiscence and reduce
      depression by increasing social interaction. The benefits to residents, their
      families, and care staff are discussed and the relevance to nursing practice
      highlighted.

PMID- 16890103
TI  - Nurses' advance care planning communication: an investigation.
AB  - This article presents a descriptive study about nurses' (N = 74) advance
      directive communication practices with hospitalized older patients. The research
      surveyed advance directive communication practices by using a self-administered
      questionnaire. Advance directive communication was measured with 7 subscales:
      initiation of the topic, disclosure of information, identification of a surrogate
      decision maker, discussion of treatment options, elicitation of patient values,
      interaction with family members, and collaboration with other health care
      professionals. Results suggest that nurses' communication regarding advance
      directives reflects a broader process of advance care planning and that age,
      years of experience, and personal experience with advance directives are
      associated with communication practices.

PMID- 16890105
TI  - Assessment of attention in Alzheimer's disease.
AB  - Intact memory is critical to maintaining cognitive vitality and independent
      functional status, and impaired memory is a major risk factor for nursing home
      admission. It is essential that all people who work with elders in any setting
      (community, acute care hospital, or long-term care facility) identify early
      subtle changes in memory such as impaired attention and institute proper care in
      a timely manner. This article describes attention and how it is related to
      impaired memory. It presents methods of assessing impaired attention in older
      adults and interventions to support attention in older adults.

PMID- 16890104
TI  - The effect of a feeding skills training program for nursing assistants who feed
      dementia patients in Taiwanese nursing homes.
AB  - A quasi-experimental 2-group repeated-measures design was used to test the impact
      of a feeding skills training program on 67 nursing assistants (treatment group n
      = 31; control group n = 36) regarding their knowledge, attitudes, perceived
      behavior control, intentions, and behaviors in feeding dementia patients. The
      treatment group received a feeding skills training program. Nursing assistants'
      knowledge, attitudes, perceived behavior control, and intentions were measured
      before (Pretest) and after the program (Posttest 1), and again 4 weeks later
      (Posttest 2). Nursing assistants (treatment group n = 20; control group n = 16)
      and the same number of dementia patients were measured on feeding behaviors
      during mealtimes before and after the training. The treatment group had
      significantly more knowledge (P < .001), greater intention to feed (P = .05), and
      better behaviors toward feeding dementia patients (P = .009) than the control
      group. There were no significant differences between the groups in attitude (P =
      .85), intention beliefs (P = .11) or perceived behavior control (P = .99). Thus,
      the intervention was effective at changing knowledge, intention, and behaviors
      among nursing assistants.

PMID- 16890106
TI  - How do self-care routines of nursing home residents compare with past self-care
      practices?
AB  - This article compares the self-care routines of nursing home residents with those
      customarily practiced when individuals were able to care for themselves.
      Participants were 20 nursing home residents, their spouses, and nursing
      assistants. Self-care routines were assessed using the Self-maintenance Habits
      and Preferences in Elderly (SHAPE) questionnaire. More items change than remain
      the same. Items most likely to change are those dealing with timing or duration.
      Routines become more simplified after admission and reflect the increased frailty
      of residents. Self-care becomes more important overall. Spouses are unable to
      indicate whether current and past self-care practices are the same slightly over
      half of the time, but nursing assistants are almost totally lacking in the
      knowledge of previous self-care routines. Knowledge of changes in self-care
      routines can be used to guide interventions to bring past and current practices
      into greater concordance.

PMID- 16890107
TI  - Registry of the International Society for Heart and Lung Transplantation: twenty
      third official adult heart transplantation report--2006.

PMID- 16890108
TI  - Registry of the International Society for Heart and Lung Transplantation: twenty
      third official adult lung and heart-lung transplantation report--2006.

PMID- 16890109
TI  - Registry of the International Society for Heart and Lung Transplantation: ninth
      official pediatric heart transplantation report--2006.

PMID- 16890110
TI  - Registry of the International Society for Heart and Lung Transplantation: ninth
      official pediatric lung and heart-lung transplantation report--2006.

PMID- 16890111
TI  - Coronary vasomotor response to phenylephrine in heart transplant patients.
AB  - BACKGROUND: Coronary vasomotor responses to sympathetic stimulation vary with
      endothelial-layer integrity or presence of atherosclerosis. Our study objective
      was to assess the effects of phenylephrine-induced alpha-adrenergic stimulation
      on coronary vasomotion in heart transplant recipients with and without graft
      atherosclerosis. METHODS: Intracoronary phenylephrine (alpha(1)-selective
      agonist) was injected in 6 control subjects, 9 recipients with angiographically
      normal coronary arteries and 8 recipients with mild or moderate atherosclerosis.
      Coronary flow velocity was measured using a Doppler guide-wire. The diameters of
      3 epicardial segments of the left coronary artery and coronary blood flow and
      resistance were assessed at baseline, after infusion of increasing acetylcholine
      doses (10(-7) and 10(-6) mol/liter) and after phenylephrine (150- to 200-microg
      bolus). Systemic and coronary hemodynamic parameters were measured immediately
      after acetylcholine and 1, 3, 5, 7, 10 and 15 minutes after phenylephrine.
      RESULTS: Phenylephrine induced similar significant increases in rate pressure
      product in the 3 groups. Acetylcholine induced epicardial vasodilation in
      controls and vasoconstriction in transplant recipients. Phenylephrine induced
      epicardial vasodilation in controls and in angiographically normal recipients;
      subsequent vasoconstriction occurred in this last group. In the recipients with
      angiographic abnormalities, sustained vasoconstriction occurred. At peak
      phenylephrine effect, coronary blood flow (CBF) increased significantly (p <
      0.001 vs baseline) in all 3 groups. Coronary resistance decreased in the 3 groups
      but the decrease was smaller in the recipients with angiographic abnormalities (p
      < 0.05 vs controls). CONCLUSIONS: In heart transplant patients, graft
      atherosclerosis unmasks the direct coronary vasoconstricting effects of
      pharmacologic alpha-adrenergic stimulation.

PMID- 16890112
TI  - Surveillance for transplant coronary artery disease in infant, child and
      adolescent heart transplant recipients: an intravascular ultrasound study.
AB  - BACKGROUND: Transplant coronary arteriopathy (TCAD) limits graft survival after
      heart transplantation in adult and pediatric heart transplant recipients.
      Intravascular ultrasound (IVUS) provides a highly sensitive technique to detect
      TCAD. However, its use to determine factors associated with TCAD in pediatric
      recipients has been limited and its utility in surveillance for symptomatic TCAD
      in this population is uncertain. METHODS: One hundred fifty-eight IVUS studies
      from 66 patients (27 <1 year and 39 >1 year at time of transplant) were performed
      12 to 144 months after transplantation within the routine surveillance for TCAD.
      Maximal intimal thickness (MIT) and intimal index (II) were measured, and the
      Stanford classification was utilized to grade overall severity of disease. Mixed
      repeated-measures linear regression models were used to investigate the main and
      interaction effects of age at transplant, age at time of study, time since
      transplant and rejection events. RESULTS: Age at catheterization (p = 0.0002),
      transplantation at age >12 months (p = 0.014), increasing time after
      transplantation (p = 0.021) and the combination of late rejection and hemodynamic
      compromising rejection (p = 0.05) were significantly associated with increasing
      MIT. Age at catheterization (p = 0.0149), transplantation at age >12 months (p =
      0.016), time from transplantation (p = 0.0076) and rejection with hemodynamic
      compromise (p = 0.01) were significantly associated with increased II. Nine
      patients developed evidence of severe (Stanford Class 4) TCAD by IVUS, but only 2
      (22%) developed symptomatic TCAD, with a median follow-up of 44 months. Four of
      the 7 patients who developed symptomatic TCAD had no or minimal TCAD (Stanford
      Class 0 or 1) on a surveillance examination within 18 months of the onset of
      symptoms. CONCLUSIONS: Increasing time after transplantation, recipient age and
      age at transplantation as well as rejection history, especially rejection with
      hemodynamic compromise, are associated with the development of TCAD as detected
      by IVUS in pediatric heart transplant recipients. Severe TCAD detected by IVUS
      does not often rapidly progress to symptomatic TCAD. Symptomatic TCAD may develop
      rapidly even in patients with little or no TCAD detected by IVUS.

PMID- 16890113
TI  - Cyclosporine C2 target levels and acute cellular rejection after lung
      transplantation.
AB  - BACKGROUND: Acute pulmonary allograft rejection (AR) is the most important risk
      factor for bronchiolitis obliterans syndrome (BOS), which is associated with
      reduced quality of life and decreased survival after lung transplantation (LTx).
      Trough (C0) cyclosporine (CyA) levels have a poor correlation with area-under-the
      curve (AUC) measurements of cyclosporine exposure compared with 2-hour post-dose
      (C2) levels, but there are no published guidelines for C2 levels after LTx.
      Hence, we assessed the utility of C2 target levels to prevent AR. METHODS: Fifty
      consecutive de novo LTx patients (bilateral, 44; single, 3; heart-lung, 3; cystic
      fibrosis, 20; non-cystic fibrosis, 30) managed with CyA were assigned target C2
      levels as follows: >800 microg/liter within 48 hours; >1,200 microg/liter from
      Week 1 to Month 1; >1,000 microg/liter in Month 2; >800 microg/liter in Month 3;
      >700 in microg/liter in Months 3 to 6; and >600 microg/liter thereafter.
      Surveillance transbronchial biopsies (TBBxs) were performed at 3, 6, 9 and 12
      weeks. An intention-to-treat analysis was performed and results compared with our
      historic controls managed by C0 monitoring. RESULTS: Fifteen of 50 (30%) LTx
      recipients developed AR on 23 of 171 TBBxs (Grade A2:A3 = 21:2) during follow-up
      (mean +/- SD) of 1,185 +/- 426 days (range, 16 to 1,790 days). Eighteen of 23 AR
      episodes occurred after sub-target C2 levels. The 30-day, 1-, 3- and 5-year
      actuarial survival rates were 98%, 94%, 82% and 77%, respectively. Thirteen of 48
      (27%) evaluable LTx recipients developed BOS with 1-, 3- and 5-year freedom-from
      BOS rates of 96%, 79% and 59%, respectively. Only 1 patient developed severe
      renal dysfunction. CONCLUSIONS: Achieving and maintaining target C2 levels after
      LTx is associated with reduced rates of AR and BOS, preservation of renal
      function, and excellent short-term survival rates when compared with historic
      controls.

PMID- 16890114
TI  - Similar efficacy and safety of enteric-coated mycophenolate sodium (EC-MPS,
      myfortic) compared with mycophenolate mofetil (MMF) in de novo heart transplant
      recipients: results of a 12-month, single-blind, randomized, parallel-group,
      multicenter study.
AB  - BACKGROUND: Enteric-coated mycophenolate sodium (EC-MPS, myfortic) is an advanced
      formulation that delays the release of mycophenolic acid (MPA). Its efficacy and
      safety has been proven in several clinical trials in renal transplantation.
      METHODS: In a single-blind, multicenter trial, a total of 154 de novo heart
      transplant patients were randomized to either EC-MPS 1,080 mg twice daily or
      mycophenolate mofetil (MMF) 1,500 mg twice daily. Eligible patients included men
      or women aged 18 to 65 years, undergoing primary heart transplantation, who were
      treated with cyclosporine microemulsion and corticosteroids as basic
      immunosuppression. The primary study objective was to investigate the incidence
      of biopsy-proven and treated acute rejection, graft loss or death (defined as
      treatment failure) for EC-MPS vs MMF during the first 6 months of treatment in de
      novo heart transplant recipients. Secondary objectives included assessment of the
      overall safety and tolerability of EC-MPS vs MMF in the study population.
      RESULTS: The primary efficacy variable, treatment failure at 6 months, was
      similar for both treatments: 52.6% for EC-MPS and 57.9% for MMF (2-sided 95%
      confidence interval [CI]: -21.0% to 10.4%). At 12 months, treatment failure was
      57.7% for EC-MPS and 60.5% for MMF (2-sided 95% CI: -18.4 to 12.7), and death and
      graft loss rate was 5.1% vs 9.2% for EC-MPS and MMF at 12 months, respectively (2
      sided 95% CI: -12.2 to 4.1). The overall safety profile was similar for both
      groups. Significantly more patients on MMF had two or more study medication dose
      reductions during the treatment period. CONCLUSIONS: These 6- and 12-month
      results show that EC-MPS is therapeutically similar to MMF in de novo heart
      transplant recipients and has a comparable safety profile.

PMID- 16890115
TI  - Association of heart rate recovery and maximum oxygen consumption in patients
      with chronic congestive heart failure.
AB  - BACKGROUND: Peak oxygen consumption (peak VO2) is one of the strongest predictors
      of mortality in patients with congestive heart failure (CHF). In contrast to
      measurements of peak VO2, which requires analysis of expired gases, heart rate
      recovery, defined as maximum heart rate minus heart rate at 1 minute after
      exercise, is easily obtained. The current study was undertaken to determine the
      association between peak VO2 and heart rate recovery in patients with CHF.
      METHODS: Retrospective data on VO2 and heart rate recovery were analyzed in 296
      patients with CHF secondary to left ventricular systolic dysfunction (left
      ventricular ejection fraction [LVEF] <50%) who had undergone cardiopulmonary
      exercise testing (CPET). Patients exercised on a treadmill using a graded work
      rate protocol with the work increasing to a symptom-limited maximum. Peak oxygen
      consumption was defined as the highest value of oxygen uptake attained in the
      final 20 seconds of exercise when the respiratory exchange ratio was >1.0.
      RESULTS: Heart rate recovery and peak VO2 correlated moderately (r = 0.47, p <
      0.001). The degree of correlation was similar in patients receiving beta-blockers
      (r = 0.47, p < 0.001) and those not receiving beta-blockers (r = 0.49, p <
      0.001). CONCLUSIONS: Although heart rate recovery and peak VO2 correlated
      moderately, from a clinical standpoint, this finding is probably not strong
      enough to use heart rate recovery in lieu of peak VO2. This modest correlation of
      two independent predictors of outcome may suggest their usefulness when combined
      in a multivariate score.

PMID- 16890116
TI  - Grafting an acellular 3-dimensional collagen scaffold onto a non-transmural
      infarcted myocardium induces neo-angiogenesis and reduces cardiac remodeling.
AB  - BACKGROUND: This study was designed to determine whether tissue engineering could
      be used to reduce ventricular remodeling in a rat model of non-transmural, non-ST
      elevation myocardial infarction. METHODS: We grafted an acellular 3-dimensional
      (3D) collagen type 1 scaffold (solid porous foam) onto infarcted myocardium in
      rats. Three weeks after grafting, the scaffold was integrated into the myocardium
      and retarded cardiac remodeling by reducing left ventricular (LV) dilation. The
      LV inner and outer diameters, measured at the equator at zero LV pressure,
      decreased (p < 0.05) from 11,040 +/- 212 to 9,144 +/- 135 microm, and 13,469 +/-
      187 to 11,673 +/- 104 microm (N = 12), after scaffold transplantation onto
      infarcted myocardium. The scaffold also shifted the LV pressure-volume curve to
      the left toward control and induced neo-angiogenesis (700 +/- 25 vs 75 +/- 11 neo
      vessels/cm2, N = 5, p < 0.05). These vessels (75 +/- 11%) ranged in diameter from
      25 to 100 microm and connected to the native coronary vasculature. Systemic
      treatment with granulocyte-colony stimulating factor (G-CSF), 50 microg/kg/day
      for 5 days immediately after myocardial injury, increased (p < 0.05) neo-vascular
      density from 700 +/- 25 to 978 +/- 57 neo-vessels/cm2. CONCLUSIONS: A 3D collagen
      type 1 scaffold grafted onto an injured myocardium induced neo-vessel formation
      and reduced LV remodeling. Treatment with G-CSF further increased the number of
      vessels in the myocardium, possibly due to mobilization of bone marrow cells.

PMID- 16890117
TI  - Donor-specific cytotoxic hyporesponsiveness associated with high interleukin-10
      messenger RNA expression in cardiac allograft patients.
AB  - BACKGROUND: After transplantation, CD4+CD25+FOXP3+ and interleukin (IL) 10
      producing regulatory cells might regulate immune responses toward donor antigens.
      In this study, we determined whether cardiac allograft recipients show donor
      specific hyporesponsiveness and studied the underlying mechanisms. METHODS: We
      analyzed the donor-specific T-cell responses by mixed lymphocyte reactions and
      limiting dilution assays to define whether cardiac allograft recipients (n = 21)
      show proliferative and cytotoxic hyporesponsiveness to donor antigens long after
      transplantation (range, 1.5-7 years). The mechanisms controlling immune
      responses, that is, FOXP3+/GITR+ T cells, and IL-10-producing cells, were studied
      by quantitative real-time polymerase chain reaction. RESULTS: In the presence of
      a proliferative response to donor antigens, no cytotoxic responsiveness could be
      measured in a number of patients in the absence (73%) and presence of exogenous
      IL-2 (29%), IL-15 (31%), and IL-15 plus IL2Ralpha blockade (88%). Overall, the
      cytotoxic response to donor cells was significantly lower than the reactivity to
      third-party cells after the addition of IL-2 (p = 0.004) and IL-15 plus IL2Ralpha
      blockade (p < 0.001). After donor stimulation, the peripheral blood mononuclear
      cells expressed higher messenger RNA (mRNA) levels of IL-10, but not of FOXP3 or
      GITR, than after third-party stimulation (p = 0.003). Moreover, the IL-10 mRNA
      expression was inversely correlated with the donor-specific cytotoxic
      responsiveness (p = 0.01). CONCLUSIONS: A significant proportion of patients
      showed donor-specific cytotoxic hyporesponsiveness long after heart
      transplantation, which was associated with high mRNA levels of IL-10 but not of
      FOXP3 or GITR. This observation suggests that IL-10-producing cells participate
      in the donor-specific cytotoxic hyporeactivity.

PMID- 16890118
TI  - Effect of the free radical scavenger MCI-186 on pulmonary ischemia-reperfusion
      injury in dogs.
AB  - BACKGROUND: Free radical scavengers and superoxide dismutase have been found to
      protect against cerebral ischemic damage, and it was suggested that oxygen free
      radicals contribute to ischemia-reperfusion injury induced by cerebral ischemic
      damage. MCI-186 (3-methyl-1-phenyl-2-pyrazolin-5-one) is a potent scavenger and
      inhibitor of hydroxyl radicals and protective agent of peroxidative injury. The
      purpose of this study was to evaluate the effects of MCI-186 on pulmonary
      ischemia-reperfusion injury in a simulated transplanted lung model. METHODS:
      Fourteen dogs were divided into two groups (n = 7 each). In the MCI group, MCI
      186 was continuously administered at 3 mg/kg/hour intravenously (IV) from 30
      minutes before reperfusion until 30 minutes after reperfusion (total
      administration time 1 hour). Vehicle was administered in the control group. Warm
      ischemia was induced for 3 hours by clamping the left pulmonary artery and veins.
      Simultaneously, the left stem bronchus was bisected and then anastomosed before
      reperfusion. The right pulmonary artery was ligated 15 minutes after reperfusion,
      and the right stem bronchus was then bisected. RESULTS: The respiratory gas
      exchange, hemodynamic changes, wet-to-dry weight ratio (WDR) and malondialdehyde
      (MDA) concentration in the tissue were significantly improved (p < 0.05) in the
      MCI group. The histologic damage was more severe in the control group and
      polymorphonuclear neutrophil (PMN) infiltration was reduced in the MCI group.
      CONCLUSION: MCI-186 has a protective effect on pulmonary ischemia-reperfusion
      injury through the inhibition of lipid peroxidation.

PMID- 16890119
TI  - What is the attitude of hospital transplant-related personnel toward donation?
AB  - The attitude of health-care workers, especially in transplant-related services,
      is fundamental in the process of organ procurement. In this study we examine the
      attitude of workers in transplant-related services toward cadaveric organ
      donation and transplantation (ODT) in a third-level hospital in Spain. A random
      sample was stratified according to type of service and job category (n = 309)
      among personnel in transplant-related services (organ procurement units,
      transplant units and follow-up units). Attitude toward cadaveric organ donation
      was evaluated using a validated psychosocial questionnaire. Seventy percent (n =
      215) of respondents were found to be in favor of donation, as opposed to 30%
      against or undecided (n = 94). Regarding job category, attitude was most
      favorable among physicians (86%, n = 99; p = 0.000). With respect to type of
      service, attitude tended to be more negative in organ procurement units and more
      positive in the follow-up units of transplanted patients (41% vs 81%, p = 0.013).
      Upon analysis of the psychosocial variables, significant results were found with
      respect to the following factors: (1) age (39 vs 42 years, p = 0.007); (2) having
      discussed ODT with family members or with a partner (p = 0.007); (3)
      understanding of the concept of brain death (p = 0.001); (4) attitude toward
      carrying out an autopsy (p = 0.001); and (5) concern about the possibility of
      mutilation after organ extraction. Attitude toward cadaveric donation was lower
      than expected among personnel in transplant-related services, especially among
      ancillary personnel and workers in organ procurement units.

PMID- 16890120
TI  - Evaluation of sympathetic re-innervation in heterotopic cardiac transplants by
      iodine-123-metaiodobenzylguanidine (I-123-MIBG) imaging.
AB  - Scintigraphy using iodine-123-metaiodobenzylguanidine (I-123-MIBG) has been used
      to demonstrate that >50% of orthotopically transplanted hearts undergo partial
      cardiac sympathetic re-innervation and that this occurs no earlier than 1 year
      post-transplant. This study used planar and singe-photon emission computed
      tomography (SPECT) I-123 MIBG scintigraphy to show that cardiac re-innervation
      was not detectable in any of the 8 patients studied 1.1 to 6.3 years post
      heterotopic transplantation. Thus, potential for cardiac re-innervation varies
      according to the type of procedure performed.

PMID- 16890121
TI  - Small-cell lung carcinoma of recipient origin after bilateral lung
      transplantation for cystic fibrosis.
AB  - Bronchial carcinoma, usually of the non-small-cell type, is uncommon after lung
      transplantation and occurs predominantly in single-lung transplant ex-smoker
      recipients on their native lung. Bronchial carcinoma of donor origin is much
      rarer. We report the case of a small-cell lung carcinoma of recipient origin that
      occurred 12 months after a bilateral lung transplantation for cystic fibrosis in
      a 25-year-old woman who was a non-smoker. The tumor was of recipient origin, due
      to a gender mismatch between donor and recipient. This unusual observation
      corroborates the hypothesis of chimerism of the bronchial epithelium after lung
      transplantation.

PMID- 16890123
TI  - Fulminant acute cellular rejection with negative findings on endomyocardial
      biopsy.
AB  - We present a case of a heart transplant recipient who had new-onset heart
      failure, repeatedly unremarkable endomyocardial biopsies, a negative evaluation
      for humoral rejection, and subsequently autopsy findings of severe sub-epicardial
      myocyte necrosis with classic cellular rejection. The sub-endocardial layer was
      free from rejection. The implications for clinical management, in the context of
      a diagnosis of "biopsy-negative rejection with hemodynamic compromise," include
      the need to consider intensification of immunosuppression with regimens similar
      to those used for biopsy-proven rejection.

PMID- 16890122
TI  - Mycobacterium abscessus chest wall and pulmonary infection in a cystic fibrosis
      lung transplant recipient.
AB  - Mycobacterial infections are increasingly recognized in cystic fibrosis (CF)
      patients before transplant; however, knowledge about the clinical significance or
      spectrum of infections observed with mycobacterial infections in lung transplant
      recipients is still evolving. Herein, we report a case of infection with
      Mycobacterium abscessus in a CF lung transplant recipient. Despite aggressive
      treatment before and peri-operatively with anti-mycobacterial therapy, the
      patient developed skin and soft tissue infection of the incision and of bilateral
      breast implants, eventually leading to disseminated pulmonary infection and
      death. This report highlights the potential for M abscessus to cause post
      transplant disease in CF patients undergoing lung transplant, despite peri
      operative anti-mycobacterial therapy. Thus, pre-transplant colonization with M
      abscessus should be viewed as a strong relative, if not absolute,
      contraindication to lung transplantation. The combination of the virulent pre
      transplant pathogen M abscessus and foreign bodies in the chest likely acted
      synergistically to contribute to the unfortunate outcome in this patient.

PMID- 16890124
TI  - Successful combined heart and kidney transplantation in a patient with sickle
      cell anemia.
AB  - Little is known about the management of dual-organ transplantation for sickle
      cell disease (SCD)-related complications. In this case study, we report the
      successful outcome of combined heart and kidney transplantation in a patient with
      SCD. The recipient was a 33-year-old man with homozygous SCD, who developed end
      stage heart and renal failure requiring combined heart and kidney
      transplantation. The patient was managed with pre-operative blood transfusion and
      moderate hypothermic cardiopulmonary bypass, with limited peri-operative
      complications. During the first 6 months there was one episode of acute heart
      rejection without concomitant renal rejection. Eighteen months after surgery, the
      patient is at home without vaso-occlusive crises or septic complications. Heart
      and renal allograft function is preserved, without coronary artery vasculopathy,
      but with asymptomatic moderate transplant renal artery stenosis. SCD is managed
      by periodic transfusion. This case study demonstrates that combined heart and
      kidney transplantation is feasible in patients with SCD. Careful attention to
      peri- and post-operative management is required.

PMID- 16890125
TI  - Does decreased taurine participate in reduced exercise capacity after heart
      transplantation?

PMID- 16890126
TI  - Heart allograft rejection of the humoral type is a continuing "rheum-like"
      process.

PMID- 16890127
TI  - The styrylpyridine dye for the silane sol-gel transition studies by time
      dependent fluorescence.
AB  - A trans-4-(p-N,N-dimethylaminostyryl)-N-vinylbenzylpyridinium chloride (vbDMASP)
      fluorescence probe was optimized in ground and excited state as a function of
      change in the microenvironment polarity, using the Amsol HyperChem program
      package. In the calculations, protic and aprotic solvents were used. On this
      basis a change in the molecule geometry after excitation, depending on the
      surrounding solvent, was determined. Absorption and steady-state fluorescence
      spectra of vbDMASP in the solvent of different polarity and in the model water
      glycerol solutions were also recorded. On the basis of Stokes' shift change with
      the Onsager polarity scale a change in the dipole moment of the probe during
      transition from ground to excited state, in protic and aprotic solvents was
      determined. Since during the sol-gel transition of tetraethylorthosilane in the
      acidic environment both polarity and viscosity of the microenvironment change the
      vbDMASP probe was applied and fluorescence time-resolved measurements were done.
      On this basis the correlations between the results of time-resolved measurements
      for the multichromophoric probe applied in the gelation process and molecular
      optimization data are discussed.

PMID- 16890128
TI  - Analysis of pigments and coverings by X-ray diffraction (XRD) and micro Raman
      spectroscopy (MRS) in the cemetery of Tutugi (Galera, Granada, Spain) and the
      settlement convento 2 (Montemayor, Cordoba, Spain).
AB  - This paper focuses on the identification of the composition of the coverings and
      pigments of two archaeological sites. The sites researched here lie in Andalusia
      and show two contexts, which have a highly symbolic and ritual meaning. The
      first, Convento 2 (Montemayor, Cordoba), dates back to the period of formation of
      the Iberian Culture (VIIth century b.c.). The second is the cemetery of Tutugi
      (Galera, Granada), of the mid-Iberian period (IVth century b.c.). The analytical
      procedure consisted in combined and complementary use of XRD and MRS. This
      allowed to identify the materials used, namely hematite, goethite, coal, gypsum
      and calcite. Identification of these materials proves essential for the
      restoration and musealization of both archaeological sites.

PMID- 16890129
TI  - Right care, right now: the NICU contributions.

PMID- 16890130
TI  - A primer on antenatal testing for neonatal nurses: part 1. Tests used to predict
      preterm labor.
AB  - Parents and healthcare providers are challenged to understand the mechanisms of,
      and predictors for preterm delivery. In addition to the epidemiologic
      implications, on a practical level, the ability to predict preterm delivery may
      help the neonatal team triage to assure bed availability, and to predict and
      provide appropriate staffing for new admissions. On an individual patient level,
      understanding the maternal history, including antenatal risk factors and relevant
      monitoring and testing, is an important foundation for subsequent neonatal care.
      A number of new diagnostic testing tools are being used in obstetric practice to
      enhance the ability to predict preterm delivery. The results of fetal fibronectin
      and ultrasound measurement of cervical length are increasingly used to triage
      obstetrical patients. Results of these tests may prompt transfer to a tertiary
      facility. Part 1 of this 2-part series will describe antenatal testing techniques
      used to predict preterm delivery (PTD), as well as highlight the emerging
      developments in maternal serum testing. Further, a recent treatment option for
      preterm labor, 17 alpha-hydroxyprogesterone caproate, will also be discussed.

PMID- 16890131
TI  - Examining the newborn with an open spinal dysraphism.
AB  - Spinal dysraphism includes a constellation of frequent and potentially complex
      malformations of the spine and spinal cord. Open spinal dysraphisms, the majority
      of which are myelomeningoceles, have a number of associated morbidities that
      require both immediate and lifelong medical care. The role of the neonatal nurse
      includes the immediate stabilization of the affected infant, systematic
      examination of the malformation, and implementation of evidence-based protocols
      to ameliorate the associated medical problems. Coordination of care and
      communication and support of the family are essential aspects of care. This
      article reviews the embryology of open spinal dysraphisms and the steps needed to
      stabilize and evaluate affected infants.

PMID- 16890132
TI  - Case report of massive fetomaternal hemorrhage and a guideline for acute neonatal
      management.
AB  - Massive fetomaternal hemorrhage resulting in profound anemia and shock is
      associated with high perinatal morbidity and mortality. Although diagnosis before
      delivery is difficult, the clinical index of suspicion rises when a woman
      presents with history of decreased or absent fetal movements and antenatal
      monitoring shows a sinusoidal rhythm strip. The diagnosis can be made quickly by
      demonstration of fetal red blood cells in the maternal circulation and there is
      consistent recommendation in the literature to immediately order a Kleihauer
      Betke test. Clinical manifestations of a fetomaternal hemorrhage depend on the
      volume of blood lost and the rate with which it occurred. The severely
      compromised anemic infant indicative of acute hemorrhage will be pale with
      gasping respirations and signs of circulatory shock. Immediate intervention with
      volume resuscitation is crucial for optimal outcome. This article describes a
      patient with massive fetomaternal hemorrhage and subsequent devastating neonatal
      complications. The focus of this article is to provide clinical guidance for the
      management and care of the infant affected by profound anemia.

PMID- 16890133
TI  - Pilot study to prevent early-onset Group B Streptococcal disease in newborns.
AB  - PURPOSE: The purpose of this study was to: 1) examine the occurrence of early
      onset Group B Streptococcal (GBS) disease in newborns, and 2) describe the
      relationship between early-onset GBS disease in the newborn and the number of
      doses of antibiotics the mother received before delivery. SUBJECTS: Women with a
      positive Group B Streptococcus screening culture were added to the study based on
      the inclusion criteria and further grouped based on the number of doses of
      intrapartum antibiotics received. The mothers and infants in Group 1 received
      only 1 dose of intrapartum antibiotics; Group 2 received > or =2 doses of
      intrapartum antibiotics. The sample consisted of a total of 128 women and their
      infants. DESIGN AND METHODS: This pilot study used a descriptive correlational
      design. Data were obtained over a 6-month period by a retrospective chart review.
      Descriptive statistics were used to characterize the demographic data and chi(2)
      statistical analysis was done to compare the frequency of early-onset GBS disease
      in each group to determine if there were differences between groups. RESULTS: The
      Pearson chi(2) value for comparing the 2 groups was 0 with 1 degree of freedom
      indicating no difference of probability outcome between the 2 groups.
      CONCLUSIONS: There were no differences found in the incidence of early-onset GBS
      disease in newborns when a GBS positive pregnant woman received 1 or 2 doses of
      intrapartum antibiotics. These data provide further supporting evidence for the
      Centers for Disease Control and Prevention's recommendations that were based on
      the premise that vertical transmission of GBS will be greatly reduced by
      administration of 1 dose of intrapartum antibiotics at least 4 hours before
      delivery to expectant mothers.

PMID- 16890134
TI  - The Apgar score.
AB  - The Apgar score provides a convenient shorthand for reporting the status of the
      newborn infant and the response to resuscitation. The Apgar score has been used
      inappropriately to predict specific neurologic outcome in the term infant. There
      are no consistent data on the significance of the Apgar score in preterm infants.
      The Apgar score has limitations, and it is inappropriate to use it alone to
      establish the diagnosis of asphyxia. An Apgar score assigned during resuscitation
      is not equivalent to a score assigned to a spontaneously breathing infant. An
      expanded Apgar score reporting form will account for concurrent resuscitative
      interventions and provide information to improve systems of perinatal and
      neonatal care.

PMID- 16890135
TI  - New insights on inflammation in chronic kidney disease-genetic and non-genetic
      factors.
AB  - Cardiovascular disease (CVD) remains the major cause of morbidity and mortality
      in chronic kidney disease (CKD). As traditional risk factors cannot alone explain
      the unacceptable high prevalence and incidence of CVD in this population,
      inflammation (which is interrelated to insulin resistance, oxidative stress,
      wasting and endothelial dysfunction) has been suggested to be a significant
      contributor. Indeed, several different inflammatory biomarkers, such as high
      sensitivity C-reactive protein (CRP) has been shown to independently predict
      mortality in CKD patients. The causes of the highly prevalent state of
      inflammation in CKD are multiple and include factors such as volume overload, co
      morbidity, intercurrent clinical events, the dialysis procedure per se as well as
      genetic factors. Indeed, multiple cytokine DNA polymorphisms may affect the
      inflammatory state, the clinical phenotype as well as outcome in this patient
      population.

PMID- 16890136
TI  - [Polycystic kidney diseases: molecular genetics and counselling].
AB  - Autosomal dominant polycystic kidney disease (ADPKD) affects 1 newborn in 400 to
      1000 making it the most common inherited form of genetic kidney disease and an
      important cause of medical morbidity and account for about 10% of end-stage renal
      disease. Autosomal recessive polycystic kidney disease (ARPKD) is a rare
      (1/20,000 to 1/40,000) inherited disease in children characterized by the
      association of dilation of collecting ducts and biliary dysgenesis. The clinical
      spectrum is variable but it represents an important cause of renal and liver
      related morbidity and mortality in neonates and infancy. Symptoms of autosomal
      recessive PKD can begin before birth. ARPKD is genetically different from ADPKD.
      Parents who do not have the disease can have a child with the disease if both
      parents carry the abnormal gene and both pass the gene to their baby. Recently
      important advances in understanding the molecular basis of ADPKD (i.e. ADPKD1 and
      ADPKD2) and autosomal recessive PKD (i.e. PKHD1) have been done and are reported
      here. Genetic counselling is particularly advised in early onset disease
      families. It permits to determine the type of transmission, to describe the
      course and the major complications of the disease and to explain currents
      therapeutics possibilities.

PMID- 16890137
TI  - [Chronic kidney disease: do generalists and nephrologists differ in their care?].
AB  - INTRODUCTION: Chronic kidney disease (CKD) is a major public health problem. We
      report an evaluation of the CKD perception from a French family physician's (FP)
      point of view. METHODS: A questionnaire was sent to a representative and
      independently selected sample of 497 FP, i.e. 20% of the FP working in the
      administrative region Lorraine. There were 214 completed surveys, i.e. response
      rate: 43%. RESULTS: Age of FP was: < 40 years of age: 13%, 40-50: 40%, > 50: 47%.
      The geographic working place was urban: 41%, rural: 22%, urban and rural: 37%.
      Ninety-nine per cent of FP has a nephrologist, devoted to CKD referral. Twenty
      one per cent of FP has a comprehensive picture of CKD and 75% thinks that CKD
      diagnostic is difficult Thirty per cent of FP were aware of CKD guidelines. For
      FP, risk-factors for CKD were: hypertension: 93%, diabetes: 99%, age over 65:
      64%, urinary infection: 34%, hematuria/proteinuria: 78%, anaemia: 43%,
      therapeutics associated with risk of renal injury: 79%, all of these
      circumstances: 20%. The referral decision to a nephrologist was done at a mean
      creatinine clearance of 41+/-12 ml/min. Age over 80, dementia, and cancer were
      considered to be a contra-indication of renal replacement therapy, for
      respectively 30%, 69%, and 63% of FP. CME was associated with better awareness of
      guidelines, and use of clearance rather than serum creatinin. CONCLUSION: From FP
      point of view, overall awareness of CKD guidelines is low. In the context of the
      current nephrology services, greater sharing of CKD care with FP is needed.

PMID- 16890139
TI  - [Renal manifestations of systemic autoimmune disease: diagnosis and therapy].
AB  - Renal involvement is relatively common in certain systemic autoimmune diseases,
      but can be clinically silent. Active surveillance is, therefore, essential
      because the early recognition of renal involvement may influence the extent of
      renal recovery. Blood pressure control is also essential, regardless of the
      underlying disease. In systemic lupus erythematosus, therapy usually depends on
      the renal biopsy findings as not all forms of renal involvement respond in the
      same way. Typically, for aggressive disease, therapy is with steroids and a
      cytotoxic agent, usually cyclophosphamide initially and then azathioprine. In
      systemic vasculitis with renal involvement, a similar approach is adopted,
      therapy including steroids and cyclophosphamide initially and then steroids and
      azathioprine. With severe fulminant disease, plasma exchange or pulsed
      intravenous methylprednisolone is added initially. Scleroderma renal crises are
      managed by blood pressure control using angiotensin-converting enzyme inhibitors
      and other agents as required. Dialysis and transplantation can be successful in
      these conditions.

PMID- 16890138
TI  - [Cutaneous infection due to Mycobacterium chelonae in a hemodialysed patient].
AB  - We report a case of a hemodialysed patient who developed a cutaneous
      Mycobacterium chelonae infection. This infection was only localised on the left
      upper limb, downstream from the arteriovenous fistula. M. chelonae is an unusual
      human pathogen, which is present in soil, dust, and stagnant water. Various
      factors, especially immunosuppression can favour this sort of infection in
      humans. Because of the ubiquity of the mycobacterium, the source of the
      inoculation sometimes remains unknown. However, a great number of cases are
      related to nosocomial infections. The preferential localizations are cutaneous,
      ocular, and pulmonary. Some cases of cutaneous infections due to M. chelonae, or
      caused by other atypical mycobacterium, are described in renal transplantation,
      peritoneal dialysis and hemodialysis. In the case we describe here, the source of
      contamination was not identified. The outcome was favourable with clarithromycin.
      This treatment is still continued because of a reappearance of the lesions when
      treatment was discontinued.

PMID- 16890140
TI  - [The vascular network: a capital to preserve for the future].
AB  - These guidelines were constructed by the commission of dialysis of the Society of
      nephrology regarding the venous network and arteries preservation, at the
      intention of every specialist concerned by vascular access problems.

PMID- 16890143
TI  - The effect of dietary sodium intake on measures of diastolic function: increased
      relaxation or not?

PMID- 16890144
TI  - Dietary sodium intake modulates myocardial relaxation responsiveness to
      angiotensin II.
AB  - Dietary sodium alters renovascular responsiveness to angiotensin II (Ang II) in
      normal subjects. Evidence supports a connection among dietary sodium, the rennin
      angiotensin system, and myocardial function. The authors hypothesized that a
      similar relationship would exist in the heart, and that the pattern of responses
      would be qualitatively similar to the renal vasculature. Thirteen healthy
      volunteers (aged 38.6 +/- 4 years) entered a 2 week crossover design study (week
      1, high sodium diet [HS] > 200 mmol Na/day; week 2, low sodium diet [LS], < 10
      mmol Na/day) to investigate the influence of dietary sodium and Ang II on
      myocardial relaxation and renal blood flow (RBF). At the end of each study week,
      the authors assessed diastolic function (myocardial relaxation velocities [E']
      using tissue Doppler imaging) and RBF (para-aminohippurate clearance) at baseline
      and after infusion of Ang II (3 ng/kg/min x 45 min). On HS diet, E' and RBF were
      higher than on LS diet (E' 14.0 +/- 1.2 vs 12.6 +/- 1.0 cm/s, P = 0.02; RBF 596
      +/- 24 vs 563 +/- 26 mL/min, P = 0.02). Dietary sodium significantly modulated E'
      and RBF responsiveness to Ang II infusion in like manner. HS was associated with
      increased responsiveness compared with a blunted LS response (HS DeltaE' -1.4 +/-
      0.4 cm/s vs LS DeltaE' -0.1 +/- 0.3 cm/s, P = 0.02; HS DeltaRBF -135.2 +/- 13.2
      vs LS DeltaRBF -62.5 +/- 10.1 mL/min, P < 0.01). The authors describe for the
      first time that dietary sodium modulates myocardial relaxation and responsiveness
      to Ang II. It is important to consider dietary sodium intake when assessing
      diastolic function. Ang II may play a role in the interaction between dietary
      sodium and myocardial relaxation. Future research will investigate whether
      abnormalities in these mechanisms play a role in disorders of diastolic function.

PMID- 16890145
TI  - Chronic iron overload stimulates hepatocyte proliferation and cyclin D1
      expression in rodent liver.
AB  - Hepatomegaly is commonly observed in hepatic iron overload due to human
      hemochromatosis and in animal models of iron loading, but the mechanisms
      underlying liver enlargement in these conditions have received scant attention.
      In this study, male rats were treated with iron dextran or dextran alone for 6
      months. Chronic iron loading resulted in a > 50-fold increase in hepatic iron
      concentration. Both liver weights and liver/body weight ratios were increased
      approximately 2-fold in the iron-loaded rats (P < 0.001 for both). Hepatocyte
      nuclei expressing proliferating cell nuclear antigen (PCNA), a marker of S phase,
      were significantly increased in the iron-loaded livers, suggesting enhanced
      proliferation. To assess the mechanisms by which iron promotes proliferation, the
      expression of tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6,
      hepatocyte growth factor (HGF), and transforming growth factor-alpha (TGF-alpha)
      were assessed by reverse transcription-polymerase chain reaction (RT-PCR). Of
      these growth-associated factors, only TNF-alpha messenger RNA (mRNA) was
      significantly increased by iron loading (about 3-fold; P = 0.005). Because cyclin
      D1 is required for entry of hepatocytes into the cell cycle after partial
      hepatectomy or treatment with direct mitogens, levels of immunoreactive cyclin D1
      were examined and found to be significantly increased in the iron-loaded livers.
      The increase in cyclin D1 protein in the iron-loaded livers was paralleled by an
      increase in the abundance of its transcript as measured by real-time PCR. Taken
      together, these results suggest that iron is a direct mitogen in the liver and
      raise the possibility that chronic stimulation of hepatocyte proliferation may
      play a role in the pathophysiology of iron overload states.

PMID- 16890146
TI  - Desferri-Exochelin, a lipid-soluble, hexadentate iron chelator, effectively
      removes tissue iron.
AB  - Chronic iron-overload is damaging to the heart, liver, and other organs. Better
      iron chelators are needed to treat this serious medical condition. The uptake and
      distribution of the lipid-soluble, hexadentate iron chelator desferri-Exochelin
      772SM (D-Exo) is studied and its efficacy in removing iron from tissue in rodent
      models is evaluated. After an intravenous bolus of tritiated D-Exo to rats,
      counts rapidly disappeared from the blood and rapidly appeared in 15 organs
      studied, usually peaking within 15 min. There was considerable uptake in the
      heart and liver, 2 organs especially susceptible to damage from clinical iron
      overload. To assess actual decreases in cardiac and hepatic iron in response to D
      Exo, mice loaded with 42 mg of iron dextran (2100 mg/kg) were studied. Untreated,
      iron-loaded mice sacrificed 9 weeks later had a 4-fold increase in cardiac iron
      and a 20-fold increase in hepatic iron compared with controls that were not iron
      loaded. In iron-loaded mice treated with 7 mg of D-Exo intraperitoneally (i.p.) 4
      days/week for 8 weeks (total 224 mg), tissue iron, measured by atomic absorption,
      was reduced by 20% in the liver and 25% in the heart (P < 0.01 for each organ).
      During the first 8 h after a D-Exo dose, iron was excreted in the urine. Mice
      treated with D-Exo gained weight normally and showed no evidence of toxicity. In
      conclusion, in this iron-overload mouse model, D-Exo administered intravenously
      or i.p. rapidly diffuses into multiple organs, including the heart and liver, and
      effectively removes iron without apparent toxicity.

PMID- 16890147
TI  - Age and QT variability index during free breathing, controlled breathing and tilt
      in patients with chronic heart failure and healthy control subjects.
AB  - The QT variability index (QTVI) indicates temporal dispersion in myocardial
      repolarization, and a high QTVI is associated with a propensity for sudden death
      from malignant ventricular arrhythmias in subjects at high risk. In this study,
      the authors assessed the effects of free breathing, controlled breathing, and
      sympathetic stress (tilt) on the QTVI in patients with chronic heart failure
      (CHF) and healthy control subjects. The authors also examined the influence of
      age on the same variables. To obtain normative data, they calculated 95%
      confidence intervals for healthy subjects grouped according to age. Under all
      experimental conditions, the QTVI was larger in the CHF group overall and in the
      age subsets than in controls. In patients and controls, the QTVI increased
      significantly during tilt, although no differences were found between the QTVI
      measured during free and controlled breathing. In healthy controls, the following
      variables correlated significantly with the QTVI: age and baseline heart rate (P
      < 0.001). In patients with CHF, aging had no influence on the QTVI. CONCLUSION:
      Age, sympathetic stress, and CHF all tend to increase the QTVI and could
      potentially induce sudden death. Further studies should assess the usefulness of
      the QTVI as a marker predicting sudden cardiac death under the various conditions
      of risk.

PMID- 16890148
TI  - Analysis of prognostic factors in therapeutic responses to interferon in patients
      with chronic hepatitis C.
AB  - The genotype of hepatitis C virus (HCV) and the amount of HCV RNA are often used
      to predict the efficacy of interferon (IFN) therapy on chronic hepatitis C. In
      addition to these factors, there may be several factors related to the host.
      Therefore, the authors undertook a retrospective study in which physical findings
      and laboratory data before therapy were evaluated by multiple logistic analysis.
      Two-hundred and five cases with chronic hepatitis C treated with interferon were
      analyzed in this study. Sustained virological response was observed with 68
      cases. Multiple logistic analysis was performed with 29 explanatory variables
      including HCV genotype, HCV RNA, IFN types, and total dose, along with gender,
      age, alcohol consumption, body mass index (BMI), histological findings of liver
      biopsy, platelet counts, and laboratory data of serum enzymes. Analysis on the
      factors that correlated well with therapeutic efficacy revealed that genotype 2a,
      2b showed higher therapeutic responses than genotype 1b with reference to HCV
      genotypes, and higher IFN dose or lower HCV RNA levels gave better results. With
      reference to host factors, higher total protein level, lower levels of BMI, total
      bilirubin, and aspartate aminotransferase were highly correlated with therapeutic
      efficacy. HCV genotypes and HCV RNA levels have been already identified as
      prognostic factors. However, the high correlation values of BMI and the total
      protein level are new findings. It is suggested that probability estimation of
      therapeutic effects using the logistic regression equation may be a good tool for
      predicting therapeutic efficacy of IFN therapy on individual cases.

PMID- 16890149
TI  - Combined CD4/CD8 ratio in induced sputum and pulmonary function testing for non
      invasive identification of sarcoidosis.
AB  - Induced sputum is a useful noninvasive method for assessing parenchymal diseases.
      This retrospective study investigated its potential application in combination
      with functional parameters to differentiate sarcoidosis from non-sarcoid
      interstitial lung disease (NSA-ILD), especially when bronchoscopy is clinically
      contraindicated. All 120 study patients (67 sarcoidosis and 53 NSA-ILD) underwent
      both bronchoalveolar lavage (flexible fiberoptic video bronchoscope; Pentax,
      Japan) and induced sputum testing (3% NaCl, selecting plugs method, 300 cells
      differentially counted in Giemsa stained cytopreps). CD4/CD8 subsets were
      identified by a fluorescence-activator cell sorter. All patients underwent high
      resolution computerized tomography and 103 of 120 underwent transbronchial
      biopsy. Multivariate logistic regression models were applied to the data to
      predict the probability of having the sarcoidosis as a function of the
      explanatory variables: Model I contained demographic and induced sputum data, and
      Model II included demographic data and combined sputum and pulmonary function
      test results. The area under the curve was 0.899 for induced sputum parameters
      alone and 0.914 for induced sputum and pulmonary function parameters. CONCLUSION:
      The results derived from the combination of noninvasive induced sputum approach
      can be used as predictors with high specificity and sensitivity in the
      differential diagnosis of sarcoidosis.

PMID- 16890150
TI  - Change in the concentration of neutrophil elastase in bronchoalveolar lavage
      fluid during anesthesia and its inhibition by cholesterol sulfate.
AB  - Cholesterol sulfate (CS) in the gastrointestinal tract exhibits a mucosal
      protective activity in mouse ulcer model. To clarify the possible role of CS for
      protection from the epithelial injury due to neutrophil elastase in the
      tracheobronchi, the authors determined the concentrations of CS and neutrophil
      elastase in bronchoalveolar lavage fluid (BALF) from patients under anesthesia,
      and they examined the inhibitory activity of CS toward neutrophil elastase. The
      concentrations of CS and neutrophil elastase were determined by thin-layer
      chromatography and enzyme-linked immunosorbent assaying, respectively, and the
      effect of CS on the activity of elastase was determined with a chromogenic
      substrate. CS was found to be present in human lung, tracheal mucosa, and BALF,
      and a high synthesis of it was detected in the tracheal mucosa, in which cellular
      cholesterol sulfotransferase was induced depending on the density of tracheal
      cells. Among lipids in the tracheal mucosa, only CS was demonstrated to exhibit
      inhibitory activity toward neutrophil elastase, a powerful erosive agent in
      inflammation. The secretion of elastase from neutrophils into BALF was stimulated
      during the course of general anesthesia. In contrast, the amount of CS in BALF
      gradually decreased during anesthesia. On immune-precipitation of neutrophil
      elastase in BALF, CS was detected in the immune precipitate, which indicates a
      possible association of CS with neutrophil elastase in BALF. CONCLUSION: CS,
      which is a major acidic lipid in the tracheobronchial epithelium, might function
      as an epithelial inhibitor toward neutrophil elastase secreted in response to
      several stimuli such as anesthesia.

PMID- 16890151
TI  - What's so Bor(a)ing about Aurora-A activation?
AB  - Aurora-A kinases are highly conserved mitotic kinases required for cell division.
      The regulation of Aurora-A activity is less highly conserved and currently poorly
      understood. Work by Knoblich and coworkers in this issue of Developmental Cell
      identifies the conserved protein, Aurora Borealis (Bora), as a key regulator of
      Aurora-A activity during mitosis.

PMID- 16890152
TI  - Noisy silencing of chromatin.
AB  - Chromatin-based repression is a major mechanism for epigenetically heritable
      variation. Work in the July 21 issue of Molecular Cell quantitatively examines
      transcriptional silencing in individual yeast cells, demonstrating locus-specific
      effects and finding that different silencing mutants exhibit qualitatively
      distinct single-cell defects.

PMID- 16890153
TI  - Cytokinesis goes polo.
AB  - Temporal and spatial coordination of cytokinesis with chromosome segregation is
      key for successful cell division, but it is poorly understood. A recent article
      in Science by Pellman and coworkers (Yoshida et. al., 2006) reveals how the yeast
      polo-like kinase Cdc5 triggers Rho1/RhoA activation and the assembly of the
      contractile actin ring during anaphase.

PMID- 16890154
TI  - Canonical Wnt signaling: an unexpected new player.
AB  - Canonical Wnt signaling, below the Fz/LRP receptor complex, induces the
      stabilization of beta-catenin via an unresolved mechanism. A recent study in
      Genes & Development introduces a new player and deepens our understanding of this
      signaling relay that plays pivotal roles during embryogenesis and tumorigenesis.

PMID- 16890155
TI  - Mitotic activation of the kinase Aurora-A requires its binding partner Bora.
AB  - The protein kinase Aurora-A is required for centrosome maturation, spindle
      assembly, and asymmetric protein localization during mitosis. Here, we describe
      the identification of Bora, a conserved protein that is required for the
      activation of Aurora-A at the onset of mitosis. In the Drosophila peripheral
      nervous system, bora mutants have defects during asymmetric cell division
      identical to those observed in aurora-A. Furthermore, overexpression of bora can
      rescue defects caused by mutations in aurora-A. Bora is conserved in vertebrates,
      and both Drosophila and human Bora can bind to Aurora-A and activate the kinase
      in vitro. In interphase cells, Bora is a nuclear protein, but upon entry into
      mitosis, Bora is excluded from the nucleus and translocates into the cytoplasm in
      a Cdc2-dependent manner. We propose a model in which activation of Cdc2 initiates
      the release of Bora into the cytoplasm where it can bind and activate Aurora-A.

PMID- 16890156
TI  - A Bruno-like gene is required for stem cell maintenance in planarians.
AB  - The regenerative abilities of freshwater planarians are based on neoblasts, stem
      cells maintained throughout the animal's life. We show that a member of the Bruno
      like family of RNA binding proteins is critical for regulating neoblasts in the
      planarian Schmidtea mediterranea. Smed-bruno-like (bruli) mRNA and protein are
      expressed in neoblasts and the central nervous system. Following bruli RNAi,
      which eliminates detectable Bruli protein, planarians initiate the proliferative
      response to amputation and form small blastemas but then undergo tissue
      regression and lysis. We characterize the neoblast population by using antibodies
      recognizing SMEDWI-1 and Histone H4 (monomethyl-K20) and cell-cycle markers to
      label subsets of neoblasts and their progeny. bruli knockdown results in a
      dramatic reduction/elimination of neoblasts. Our analyses indicate that neoblasts
      lacking Bruli can respond to wound stimuli and generate progeny that can form
      blastemas and differentiate; yet, they are unable to self-renew. These results
      suggest that Bruli is required for stem cell maintenance.

PMID- 16890157
TI  - An unexpected role for IL-3 in the embryonic development of hematopoietic stem
      cells.
AB  - Cytokines are important in adult hematopoiesis, yet their function in embryonic
      hematopoiesis has been largely unexplored. During development, hematopoietic stem
      cells (HSCs) are found in the aorta-gonad-mesonephros (AGM) region, yolk sac
      (YS), and placenta and require the Runx1 transcription factor for their normal
      generation. Since IL-3 is a Runx1 target and this cytokine acts on adult
      hematopoietic cells, we examined whether IL-3 affects HSCs in the mouse embryo.
      Using Runx1 haploinsufficient mice, we show that IL-3 amplifies HSCs from E11
      AGM, YS, and placenta. Moreover, we show that IL-3 mutant embryos are deficient
      in HSCs and that IL-3 reveals the presence of HSCs in the AGM and YS prior to the
      stage at which HSCs are normally detected. Thus, our studies support an
      unexpected role for IL-3 during development and strongly suggest that IL-3
      functions as a proliferation and/or survival factor for the earliest HSCs in the
      embryo.

PMID- 16890158
TI  - Sprouty genes control diastema tooth development via bidirectional antagonism of
      epithelial-mesenchymal FGF signaling.
AB  - Unlike humans, who have a continuous row of teeth, mice have only molars and
      incisors separated by a toothless region called a diastema. Although tooth buds
      form in the embryonic diastema, they regress and do not develop into teeth. Here,
      we identify members of the Sprouty (Spry) family, which encode negative feedback
      regulators of fibroblast growth factor (FGF) and other receptor tyrosine kinase
      signaling, as genes that repress diastema tooth development. We show that
      different Sprouty genes are deployed in different tissue compartments--Spry2 in
      epithelium and Spry4 in mesenchyme--to prevent diastema tooth formation. We
      provide genetic evidence that they function to ensure that diastema tooth buds
      are refractory to signaling via FGF ligands that are present in the region and
      thus prevent these buds from engaging in the FGF-mediated bidirectional signaling
      between epithelium and mesenchyme that normally sustains tooth development.

PMID- 16890159
TI  - A viral protein that blocks Arf1-mediated COP-I assembly by inhibiting the
      guanine nucleotide exchange factor GBF1.
AB  - Many viruses modify cellular processes for their own benefit. The enterovirus 3A
      protein inhibits endoplasmic reticulum (ER)-to-Golgi transport, a function
      previously suggested to be important for viral suppression of immune responses.
      Here, we show that a virus carrying a 3A protein defective in inhibiting ER-to
      Golgi transport is indeed less virulent in mice, and we unravel the mechanism by
      which 3A inhibits this trafficking step. Evidence is provided that 3A inhibits
      the activation of the GTPase ADP-ribosylation factor 1 (Arf1), which regulates
      the recruitment of the COP-I coat complex to membranes. 3A specifically inhibits
      the function of GBF1, a guanine nucleotide exchange factor for Arf1, by
      interacting with its N terminus. By specifically interfering with GBF1-mediated
      Arf1 activation, 3A may prove a valuable tool in dissecting the early steps of
      the secretory pathway.

PMID- 16890160
TI  - Crosstalk between a nuclear receptor and beta-catenin signaling decides cell
      fates in the C. elegans somatic gonad.
AB  - beta-Catenin signaling determines the proximal-distal axis of the C. elegans
      gonad by promoting distal fate in asymmetrically dividing somatic gonad precursor
      cells (SGPs). Impaired function of the Wnt effector POP-1/TCF, its coactivator
      SYS-1/beta-catenin, and of upstream components including beta-catenin WRM-1
      causes all SGP daughters to adopt the proximal fate. Consequently, no distal tip
      cells (DTCs) that would lead differentiation of gonad arms form in the affected
      hermaphrodites. Here, we show that deficiency of the nuclear receptor NHR-25 has
      the opposite effect: extra DTCs develop instead of proximal cells. NHR-25
      knockdown restores DTC formation and fertility in pop-1 and sys-1 mutants,
      suggesting that a balance between NHR-25 and beta-catenin pathway activities is
      required to establish both proximal and distal fates. This balance relies on
      direct crossregulation between NHR-25 and the distinct beta-catenin proteins WRM
      1 and SYS-1. The nuclear receptor-beta-catenin interaction may be an ancient
      mechanism of cell-fate decision.

PMID- 16890161
TI  - Caveolin is necessary for Wnt-3a-dependent internalization of LRP6 and
      accumulation of beta-catenin.
AB  - beta-catenin-mediated Wnt signaling is critical in animal development and tumor
      progression. The single-span transmembrane Wnt receptor, low-density lipoprotein
      receptor-related protein 6 (LRP6), interacts with Axin to promote the Wnt
      dependent accumulation of beta-catenin. However, the molecular mechanism of
      receptor internalization and its impact on signaling are unclear. Here, we
      present evidence that LRP6 is internalized with caveolin and that the components
      of this endocytic pathway are required not only for Wnt-3a-induced
      internalization of LRP6 but also for accumulation of beta-catenin. Overall, our
      data suggest that Wnt-3a triggers the interaction of LRP6 with caveolin and
      promotes recruitment of Axin to LRP6 phosphorylated by glycogen synthase kinase
      3beta and that caveolin thereby inhibits the binding of beta-catenin to Axin.
      Thus, caveolin plays critical roles in inducing the internalization of LRP6 and
      activating the Wnt/beta-catenin pathway. We also discuss the idea that distinct
      endocytic pathways correlate with the specificity of Wnt signaling events.

PMID- 16890162
TI  - Tob1 controls dorsal development of zebrafish embryos by antagonizing maternal
      beta-catenin transcriptional activity.
AB  - Maternal beta-catenin and Nodal signals are essential for the formation of the
      dorsal organizer, which, in turn, induces neural and other dorsal tissue
      development in vertebrate embryos. Tob (Transducer of ErbB2) proteins possess
      antiproliferative properties and are known to influence BMP signaling, but their
      relationship to other signaling pathways and to embryonic patterning in general
      was unclear. In this study, we demonstrate that zebrafish tob1a is required for
      correct dorsoventral patterning. Mechanistically, Tob1a inhibits beta-catenin
      transcriptional activity by physically associating with beta-catenin and
      preventing the formation of beta-catenin/LEF1 complexes. Although Tob1a can also
      inhibit the transcriptional activity of the Nodal effector Smad3, its role in
      limiting dorsal development is executed primarily by antagonizing the beta
      catenin signal. We further demonstrate that Tob family members across species
      share similar biochemical properties and biological activities.

PMID- 16890163
TI  - Reversal of Hox1 gene subfunctionalization in the mouse.
AB  - In vertebrates, paralogous Hox genes play diverse biological roles. We examined
      the interchangeability of Hoxa1 and Hoxb1 in mouse development by swapping their
      protein-coding regions. Remarkably, the mice expressing the Hox-B1 protein from
      the Hoxa1 locus, and vice versa, are essentially normal. We noted, nonetheless, a
      specific facial nerve hypomorphism in hemizygous Hoxb1(A1/-) mice and decreased
      viability in homozygous Hoxa1(B1/B1) embryos. Further, we established a mouse
      line in which we have inserted the 107 bp Hoxb1 autoregulatory enhancer into the
      Hoxa1 promoter. Strikingly, the newly generated autoregulatory Hoxa1 gene can
      deliver the functionality of both paralogs in these mice, providing normal
      viability as well as proper facial nerve formation even in the Hoxb1 mutant
      background. This study affirms that subfunctionalization of the transcriptional
      regulatory elements has a principal role in the diversification of paralogous Hox
      genes. Moreover, we show that the ancestral vertebrate Hox1 gene can still be
      experimentally reconstructed.

PMID- 16890164
TI  - Localization of bicoid mRNA in late oocytes is maintained by continual active
      transport.
AB  - Localization of bicoid mRNA to the anterior of the Drosophila oocyte is essential
      to produce the Bicoid protein gradient that patterns the anterior-posterior axis
      of the embryo. Previous studies have characterized a microtubule-dependent
      pathway for bicoid mRNA localization during midoogenesis, when bicoid first
      accumulates at the anterior. We show that the majority of bicoid is actually
      localized later in oogenesis, when the only known mechanism for mRNA localization
      is based on passive trapping. Through live imaging of fluorescently tagged
      endogenous bicoid mRNA, we identify a temporally distinct pathway for bicoid
      localization in late oocytes that utilizes a specialized subpopulation of
      anterior microtubules and dynein. The directional movement of bicoid RNA
      particles within the oocyte observed here is consistent with dynein-mediated
      transport. Furthermore, our results indicate that association of bicoid with the
      anterior oocyte cortex is dynamic and support a model for maintenance of bicoid
      localization by continual active transport on microtubules.

PMID- 16890166
TI  - Lessons from large-scale gene profiling of the liver in alcoholic liver disease.
AB  - This review examines the studies pertaining to large-scale gene profiling of
      liver cells and the whole liver as performed with the aid of macro- or microarray
      gene detection technology under the conditions of alcohol-induced liver injury.
      The review emphasizes the variability of the data as a function of strain,
      species, and model of alcohol-induced liver injury employed in different studies.
      Further, the review highlights the importance of determining if changes in
      transcriptome expression are parallelled by changes in proteome and metabolome of
      the liver. On the basis of such data, models can be constructed to unravel new
      mechanistic aspects of alcohol-induced liver injury and to design novel therapies
      for alcoholic liver disease.

PMID- 16890167
TI  - Use of bone marrow cells for the development of cellular therapy in liver
      diseases.

PMID- 16890165
TI  - Quantifying the Gurken morphogen gradient in Drosophila oogenesis.
AB  - Quantitative information about the distribution of morphogens is crucial for
      understanding their effects on cell-fate determination, yet it is difficult to
      obtain through direct measurements. We have developed a parameter estimation
      approach for quantifying the spatial distribution of Gurken, a TGFalpha-like EGFR
      ligand that acts as a morphogen in Drosophila oogenesis. Modeling of Gurken/EGFR
      system shows that the shape of the Gurken gradient is controlled by a single
      dimensionless parameter, the Thiele modulus, which reflects the relative
      importance of ligand diffusion and degradation. By combining the model with
      genetic alterations of EGFR levels, we have estimated the value of the Thiele
      modulus in the wild-type egg chamber. This provides a direct characterization of
      the shape of the Gurken gradient and demonstrates how parameter estimation
      techniques can be used to quantify morphogen gradients in development.

PMID- 16890168
TI  - Up-regulation of transferrin receptor 1 in chronic hepatitis C: Implication in
      excess hepatic iron accumulation.
AB  - BACKGROUND/AIMS: : To clarify the mechanism of excess hepatic iron accumulation
      in chronic hepatitis C, we investigated the expressions of transferrin receptor 1
      and divalent metal transporter 1 in hepatocytes, both of which are involved in
      cellular iron uptake, in relation to the degree of hepatic iron accumulation and
      hepatic fibrosis by immunohistochemistrical study. METHODS: : Forty-six hepatic
      tissues with chronic hepatitis C and five normal hepatic tissues were examined.
      Chemical detection of hepatic iron accumulation was performed by Perl's Prussian
      blue stain. The immunohistochemistrical study was performed by avidin-biotin
      complex method with alkaline phosphatase. RESULTS: : In chronic hepatitis C: (1)
      Hepatic iron accumulation was significantly increased in relation to the advance
      of the fibrosis. (2) Divalent metal transporter 1 decreased significantly in
      relation to the advance of hepatic fibrosis. (3) Transferrin receptor 1
      expression was always detected, although not in normal hepatic tissues; there was
      no relation between expression levels and the degree of hepatic fibrosis.
      CONCLUSIONS: : These data demonstrated that the transferrin receptor 1 expression
      was up-regulated irrespective of the degree of hepatic iron accumulation,
      suggesting that the up-regulation of transferrin receptor 1 might act as one of
      the key mechanisms implicated in the accumulation of hepatic iron in chronic
      hepatitis C.

PMID- 16890169
TI  - Alcohol abuse and occult HBV-a risk factor for hepatocellular carcinoma.

PMID- 16890170
TI  - Should arterial infusion therapy be recommended positively for advanced
      hepatocellular carcinoma with portal vein tumor thrombosis?

PMID- 16890171
TI  - Hepatic microcirculation after continuous 7-day elevated intra-abdominal pressure
      in cirrhotic rats.
AB  - It is well known that IAP elevation, even at the level of 10mmHg used for
      laparoscopic surgery leads to an increase in portal pressure and decrease in
      portal blood flow. Since hepatic hemodynamics are already disturbed in
      cirrhotics, we decided to investigate the possible role of chronically elevated
      intra-abdominal pressure thus simulating ascites under tension-in liver perfusion
      and function in cirrhotic portal hypertensive rats. Four groups of 10 rats each
      were studied, including two control and two CCl(4)(-) induced cirrhotic groups.
      These were subdivided into normal and increased IAP. Elevation and maintenance of
      increased IAP to 20mmHg for 7 consecutive days was achieved by means of an
      intraperitonially placed balloon filled with water. Liver microcirculation was
      assessed by means of laser-Doppler technique, while venous blood samples were
      obtained for determination of the biochemical parameters of liver function.
      Cirrhotic rats showed a significant decrease in liver microcirculation in
      relation to controls (15.7+/-2.5 versus 23.2+/-2.2, p=0.001). Elevation of IAP
      led to a significant decrease (p=0.001) of liver microcirculation in both groups,
      i.e. from 15.7+/-2.5 to 12.7+/-1.7 units of flow in cirrhotics and from 23.2+/
      2.2 to 15.9+/-2.6 units of flow in control rats. Alkaline phosphatase, alanine
      aminotransferase and bilirubin concentrations were found increased in cirrhotics
      in comparison to controls (p=0.05). IAP elevation resulted in a further
      impairment of liver function, but the differences, were not statistically
      significant. In conclusion, chronically elevated IAP in cirrhotic rats is
      associated with a significant impairment of the already decreased hepatic blood
      flow due to liver cirrhosis. Thus, the possible consequences of decreased liver
      perfusion must be taken under consideration in any case of severe cirrhosis
      presented with ascites under tension.

PMID- 16890172
TI  - In vivo imaging of hepatic fatty acid metabolism in patients with nonalcoholic
      steatohepatitis using semiquantative (123)I-BMIPP liver scan.
AB  - Recent progress of studies in NASH displays multi-disciplinary characters of the
      pathogeneses. Despite these advances, the strategic use of imaging modalities
      such as CT, US, and MRI, remains a relatively low priority in clinical
      situations, because these can only visualize the presence of fatty infiltration
      to the hepatic parenchyma, impossible to figure out the dynamic function of NASH
      liver. Morphological alteration such as CT value, MR signal intensity and echo
      grade do not distinguish NASH from simple fatty liver. In this presentation, from
      a radiologic viewpoint, we show the feasibility of in vivo fatty acid imaging
      with (123)I-beta-methyl-p-iodophenyl-pentadecanoic acid (BMIPP). BMIPP is an
      (123)I labeled fatty acid analog for imaging damaged myocardium, using
      conventional nuclear imaging equipment. Under normal conditions, the energy
      source for myocardial utilization is dependent on the beta-oxidation of fatty
      acids. For energy production in ischemic myocardium, the drastic switch from
      reduced beta-oxidation of fatty acids to glucose metabolism is well known. BMIPP
      can detect the area of reduced fatty acids metabolism on myocardial imaging and
      the data can be converted into semiquantitative analysis. Therefore, we speculate
      that the use of BMIPP to in vivo hepatic imaging in NASH could highlight a lot of
      matters of NASH. Details of this presentation include: (1) Hepatic imaging with
      BMIPP; (2) Clearance of BMIPP from NASH liver; (3) semiquantitative analysis of
      hepatic BMIPP clearance and clinical features of NASH; (4) Profiles of NASH
      categorized by BMIPP imaging and (5) Preliminary data of BMIPP clearance in
      patients with Tamoxifen-induced NASH. The core of our stance in this presentation
      is searching for valuable advice on clinical use of BMIPP in patients with NASH
      from specialists in the field of HEPATOLOGY.

PMID- 16890174
TI  - CYP17 polymorphism and tamoxifen-induced hepatic steatosis.
AB  - Hepatic steatosis is a frequent complication, which sometimes develops
      nonalcoholic steatohepatitis (NASH), in breast cancer patients treated with
      tamoxifen, a potent antagonist of estrogen. Recently we reported the impairment
      of fatty acid beta-oxidation and the enhancing fatty infiltration to hepatocytes
      in aromatase deficiency (ArKO) mice as the estrogen deficiency models. This
      experimental observation let us speculate strong link between estrogen and
      hepatic steatosis. In this study, we investigated whether a polymorphism in the
      cytochrome P450c17alpha gene (CYP17), which is associated with circulating
      estrogen levels, influences the development of tamoxifen-induced hepatic
      steatosis. This consecutive study included 180 breast cancer patients undergoing
      tamoxifen treatment. Genomic DNA extracted from the peripheral blood of each
      patient was analyzed by restriction fragment length polymorphism (defined as the
      A1 and A2 alleles). The extent of hepatic steatosis was assessed by computed
      tomography (CT) as the liver/spleen (L/S) ratio. While receiving adjuvant
      tamoxifen, 57 of 180 patients developed hepatic steatosis (L/S ratio <0.9)
      without obvious changes in body mass index (BMI). We observed a significant
      association between the A2/A2 genotype and the development of hepatic steatosis
      compared with the A1/A1 genotype [odds ratio (OR), 3.60; 95% confidence interval
      (C.I.)=1.42-9.10]. The A1/A2 genotype was at an intermediately increased risk of
      hepatic steatosis (OR, 2.24; 95% C.I.=0.99-5.08). The presence of the A2 allele
      possibly increased the progression of hepatic steatosis with a gene dosage effect
      (P=0.06). Our results suggest that functional polymorphism in CYP17 may be
      involved in determining susceptibility of tamoxifen-induced hepatic steatosis.

PMID- 16890173
TI  - Interobserver variation in the histopathological assessment of nonalcoholic
      steatohepatitis.
AB  - Pathological assessment is considered as the gold standard for the diagnosis of
      nonalcoholic steatohepatitis (NASH). However, there is no agreement of
      histological features required for the diagnosis of NASH. In the present study,
      eight experienced hepatopathologists read liver biopsy specimen slides of 21
      cases of NASH and suspected NASH independently and were asked to assess
      histopathological features and render a diagnosis. Interobserver variation among
      pathologists was evaluated by kappa statistics. Significant, good agreement was
      present in evaluation of the extent of steatosis and grade of fibrosis. Agreement
      was moderate concerning the localization of steatosis, localization of fibrosis,
      and glycogen nuclei. Only slight or poor agreement was seen in evaluation of type
      of steatosis, ballooning, intralobular necroinflammatory change, portal
      inflammation, and degree of neutrophilic infiltration. Thus the agreement varied
      for histological variables. Significant, moderate agreement was seen in the
      diagnosis of NASH but agreement was poor in the diagnosis of suggestive NASH. The
      agreement for the diagnosis of NASH was not high as for the individual
      histological findings that were thought to be the basis of the diagnosis. In
      conclusion, some histological features in NASH might prove useful for the
      development of a standardized and reliable pathological diagnosis and scoring
      system.

PMID- 16890175
TI  - Protective effect of Dunaliella salina-A marine micro alga, against carbon
      tetrachloride-induced hepatotoxicity in rats.
AB  - This is the first report on the hepatoprotective potentials of marine micro algae
      Dunaliella species. Dunaliella salina, halotolarent green alga was cultivated in
      modified autotrophic medium. The alga was subjected to light and nutrient stress
      in order to accumulate (beta-carotene along with other carotenoids. Such beta
      carotene enriched yellow cells were fed to rats by mixing with regular feed at
      the dose of 2.5 and of 5.0gkg(-1) b.w. for 2 weeks. The degree of
      hepatoprotection was measured up on challenging animals with toxin (2.0gkg(-1) of
      carbon tetrachloride) by estimation of biochemical parameters like, serum
      transaminases (serum aspartate transaminase (S)AST and serum alanine transaminase
      (S)ALT), serum alkaline phosphatase and total protein. The results were compared
      to animals on normal diet and with group fed with 100mugkg(-1) b.w. of standard
      all trans beta-carotene. Among the three test groups the group fed with algae of
      5.0gkg(-1) body weight, showed maximum protection. The levels of (S)AST and
      (S)ALT was found to be 61.3+/-6.4 and 80.7+/-5.6%, against 90.8+/-10.5 and
      144.7+/-13.9% in case of standard beta-carotene. The protein contents were
      increased in case of control to 6.1+/-0.7 and the same was found to be
      significantly less in case of 5.0gkg(-1)Dunaliella fed group, which shown 5.6+/
      0.8% total protein. However, the activity of 2.5gkg(-1) was also significant
      comparatively (P<0.05). The results indicate that Dunaliella, which contains
      isomeric forms of beta-carotene can act as good antihepatotoxic when compared to
      synthetic all trans beta-carotene. Dunaliella has shown the presence of both cis
      and trans isomeric forms of beta-carotene, where as synthetic compounds contain
      only trans isomer. Hepatoprotectivity may be due to presence of various isomeric
      forms of carotene and other oxygenated carotenoids (xanthophylls) in algae.

PMID- 16890177
TI  - Zinc and hepatitis B virus vaccination.

PMID- 16890176
TI  - Effect of low-molecular-weight heparin on the commitment of bone marrow cells to
      liver sinusoidal endothelial cells in CCl(4)-induced liver injury.
AB  - BACKGROUND/AIMS: Recently liver regeneration by bone marrow transplantation has
      been proposed as an alternative source of functional liver cells. We investigate
      commitment of bone marrow cells (BMCs) to liver regeneration and the effect of
      dalteparin sodium (DS) on regeneration of the damaged liver caused by carbon
      tetrachloride (CCl(4)) administration in the mice. METHODS: Liver injury was
      produced in 8-week-old mice by treating with CCl(4) for 4 weeks. Thereafter, mice
      received a lethal dose of irradiation (10Gy) to whole body, followed by injection
      of 1x10(7) green fluorescent protein (GFP)-positive BMCs via the tail vein. DS
      (50IU/kg, intraperitoneally) was administered daily for 28 consecutive days
      starting at 1 day post-BMC transplantation. Lineage marker analysis of GFP
      positive liver cells was performed immunostaining with a CD31 antibody. RESULT:
      Four weeks after BMC transplantation, GFP-positive cells in the CCl(4)-damaged
      liver could be detected in the lobule displaying a meshwork architecture
      extending from the periportal to pericentral regions, a pattern simulating
      sinusoidal lining. This localization of GFP-positive cells suggested that these
      cells were closely associated with sinusoidal endothelial cells. By staining the
      GFP-positive cells for CD31, it was confirmed that the majority of the GFP
      positive cells are also positive for CD31. The GFP(+)CD31(+) cells were barely
      detected in the control group (1.0+/-1.2 per field). In marked contrast, a
      numerous number of GFP(+)CD31(+) cells were detected in the liver section
      obtained from the CCl(4)-induced liver damage group (3.8+/-1.3 per field, P<0.05
      versus control). The number of GFP(+)CD31(+) cells in CCl(4) plus DS-treated
      group was further increased to 8.3+/-1.3 per field (P<0.05 versus CCl(4)-induced
      liver damage group). CONCLUSION: The majority of GFP-positive BMCs was committed
      to sinusoidal endothelial cells. DS promoted BMC differentiation into sinusoidal
      endothelial cells in the CCl(4)-damaged liver.

PMID- 16890178
TI  - Ductal plate malformation, congenital hepatic fibrosis and Calori's disease are
      the same entities or not?

PMID- 16890179
TI  - Alteration of the influences of HLA classes I and II alleles on the perinatal
      hepatitis B virus infection after immunoprophylaxis in Korean children.
AB  - Some HLA alleles are known to be associated with hepatitis B virus (HBV)
      persistence. In order to find out the relationship between HLA and perinatal HBV
      infection after prophylaxis, we typed HLA classes I and II in 38 HBeAg-positive
      mothers, their children (19 succeeded and 19 failed in prophylaxis) and 198 HBsAg
      negative healthy controls. HLA-B35 (RR=2.8, p<0.03), Cw*07 (RR=2.7, p<0.02),
      DRB1*07 (RR=3.6, p<0.006), DQA1*02 (RR=3.6, p<0.02) and DQB1*02 (RR=2.4, p<0.05)
      alleles were higher and DRB1*13 (RR=0.3, p<0.03) and DPB1*0401 (RR=0.1, p<0.01)
      alleles were lower frequencies in HBeAg-positive mothers than in the control. In
      failed children to the perinatal HBV prophylaxis, HLA-Cw*0303 allele was
      significantly higher (p<0.05) and DPB1*0202 allele was lower (p<0.03) than in
      succeeded children. These results suggest the influences of certain HLA alleles
      on naturally acquired chronic HBV infection may be changed by perinatal HBV
      prophylaxis.

PMID- 16890180
TI  - The effect of norms, attitudes and habits on speeding behavior: scale development
      and model building and estimation.
AB  - In a quota sample of 334 Belgian individuals, reliable and valid scales are
      developed, that measure subjective, personal, normative and descriptive norms,
      personal identity, attitude components, perceived behavioral control, habit
      formation, behavioral intention and behavior with respect to speeding. A speeding
      behavior model is built in which the relevance of personal, descriptive and
      normative norms, the cognitive and affective attitude towards speeding, the
      affective attitude towards speed limits, and habit formation is assessed. Habit
      formation and the attitude towards speeding influence the intention towards
      speeding and self-reported speeding. Personal and to a lesser extent subjective
      and descriptive norms have a significant effect on attitudes towards speeding and
      on self-reported speeding. Recommendations for more effective and efficient anti
      speeding campaigns are formulated.

PMID- 16890182
TI  - Nanoparticles for bioimaging.
AB  - The emergence of synthesis strategies for the fabrication of nanosized contrast
      agents is anticipated to lead to advancements in understanding biological
      processes at the molecular level in addition to progress in the development of
      diagnostic tools and innovative therapies. Imaging agents such as fluorescent dye
      doped silica nanoparticles, quantum dots and gold nanoparticles have overcome
      many of the limitations of conventional contrast agents (organic dyes) such as
      poor photostability, low quantum yield, insufficient in vitro and in vivo
      stability, etc. Such particulates are now being developed for absorbance and
      emission in the near infrared region, which is expected to allow for real time
      and deep tissue imaging via optical routes. Other efforts to facilitate deep
      tissue imaging with pre-existing technologies have lead to the development of
      multimodal nanoparticles which are both optical and MRI active. The main focus of
      this article is to provide an overview of properties and design of contrast
      agents such as dye-doped silica nanoparticles, quantum dots and gold
      nanoparticles for non-invasive bioimaging.

PMID- 16890181
TI  - Anopheline breeding in river bed pools below major dams in Sri Lanka.
AB  - Anopheline mosquito larval surveys were carried out from September 2000 to August
      2002 in Mahaweli and Kelani river beds, below five major dams in the wet and
      intermediate zones of Sri Lanka, to study the prevalence of anopheline species in
      these areas. In each study site, all permanent and semi-permanent pools were
      surveyed fortnightly by dipping at 6 dips/m(2) surface area of water. Larvae were
      collected in separate containers, staged and identified at their third and fourth
      stages. During each survey, the surface area and depth of pools were recorded and
      each reading was considered as an individual observation. River bed pools below
      the dams contained stagnant clean water with a little or no aquatic vegetation.
      The majority of pools were < or =1m(2) in surface area and < or =75 cm in depth.
      Anopheline mosquito breeding was seen throughout the year in each study site. The
      average percentage of pools positive for anopheline larvae, the number of larvae
      per 100 pools and 100 dips were 14.85%, 32.34 and 9.29, respectively. Thirteen
      anopheline species, including 10 potential vectors, namely, An. barbirostris, An.
      culicifacies, An. jamesii, An. maculatus, An. nigerrimus, An. peditaeniatus, An.
      subpictus, An. tessellatus, An. vagus and An. varuna were found breeding in the
      river bed pools.

PMID- 16890183
TI  - XPS at solid-aqueous solution interface.
AB  - Application of X-ray Photoelectron Spectroscopy (XPS) to study the solid-aqueous
      solution interface is reviewed. XPS provides complementary physicochemical
      information about electrical double layer from the perspective of the solid
      surface. Experimental techniques, such as differential pumping, controlled
      adsorption/co-adsorption, freeze-drying, and fast-freezing, are discussed for
      both electrochemical and dielectric solid-solution interfaces. The use of fast
      freezing, as applied to wet pastes centrifuged from aqueous suspensions, makes it
      possible to approach a real solid-solution interface in UHV conditions. XPS data
      allow estimation of the surface density of counter-ions, surface point of zero
      charge, and in some cases the measurement of surface potential. Interfacial
      chemical reactions such as ion pair formation, specific adsorption and ligand
      exchange can be directly observed. The technique is easy to apply to any
      suspension including colloids and gels of inorganic or organic nature, and can be
      adapted for electrochemistry as complementary to traditional "emersed electrode"
      studies.

PMID- 16890184
TI  - A yeast sterol carrier protein with fatty-acid and fatty-acyl-CoA binding
      activity.
AB  - The 14-kDa sterol carrier protein 2 (SCP2) domain is present in Eukaria, Bacteria
      and Archaea, and has been implicated in the transport and metabolism of lipids.
      We report the cloning, expression, purification and physicochemical
      characterization of a SCP2 from the yeast Yarrowia lipolytica (YLSCP2).
      Analytical size-exclusion chromatography, circular dichroism and fluorescence
      spectra, indicate that recombinant YLSCP2 is a well-folded monomer. Thermal
      unfolding experiments show that SCP2 maximal stability is at pH 7.0-9.0. YLSCP2
      binds cis-parinaric acid and palmitoyl-CoA with KD values of 81+/-40 nM and 73+/
      33 nM, respectively, sustaining for the first time the binding of fatty acids and
      their CoA esters to a nonanimal SCP2. The role of yeast SCP2 and other lipid
      binding proteins in transport, storage and peroxisomal oxidation of fatty acids
      is discussed.

PMID- 16890185
TI  - Glutathione S-transferases as antioxidant enzymes: small cell lung cancer (H69)
      cells transfected with hGSTA1 resist doxorubicin-induced apoptosis.
AB  - It has been suggested that the alpha-class glutathione S-transferases (GSTs)
      protect various cell types from oxidative stress and lipid peroxidation (LPO). In
      order to examine the protective role of alpha-class GST isozyme hGSTA1-1 against
      doxorubicin (DOX)-induced lipid peroxidation, cytotoxicity, and apoptosis, human
      small cell lung cancer (SCLC) H69 cells were stably transfected with hGSTA1.
      Immunological and biochemical characterization of hGSTA1-transfected cells
      revealed the expression of functionally active hGSTA1-1 localized near the
      cellular plasma membranes. hGSTA1-transfected cells acquired significantly
      increased resistance to the DOX-induced cytotoxicity by suppressing lipid
      peroxidation levels in these cells. Overexpression of hGSTA1-1 in cells inhibited
      DOX-mediated depletion of GSH and higher GSH levels were found in DOX-treated
      hGSTA1-transfected cells as compared with empty vector-transfected controls.
      hGSTA1-1 overexpression also provided protection to cells from DOX-induced
      apoptosis by inhibiting phosphorylation of c-Jun-N-terminal kinases (JNK),
      caspase-3 activation, and by preserving the levels of anti-apoptotic protein Bcl
      2. These results are consistent with the idea that the alpha-class GSTs provide
      protection against oxidative stress by attenuating lipid peroxidation and these
      enzymes can modulate signaling for apoptosis.

PMID- 16890186
TI  - Identification of amino acid residues essential for reconstitutive activity of
      subunit IV of the cytochrome bc1 complex from Rhodobacter sphaeroides.
AB  - A region of subunit IV comprising residues 77-85 is identified as essential for
      interaction with the core complex to restore the bc(1) activity (reconstitutive
      activity). Recombinant subunit IV mutants with single or multiple alanine
      substitution at this region were generated and characterized to identify the
      essential amino acid residues. Residues 81-84, with sequence of YRYR, are
      required for reconstitutive activity of subunit IV, because a mutant with these
      four residues substituted with alanine has little activity, while a mutant with
      alanine substitution at residues 77-80 and 85 have the same reconstitutive
      activity as that of the wild-type IV. The positively charged group at R-82 and R
      84 and both the hydroxyl group and aromatic group at Y-81 and Y-83 are essential.
      The interactions between these four residues of subunit IV and residues of core
      subunits are also responsible for the stability of the complex. However, these
      interactions are not essential for the incorporation of subunit IV into the bc(1)
      complex.

PMID- 16890187
TI  - Sphingosine 1-phosphate regulates cytoskeleton dynamics: implications in its
      biological response.
AB  - The bioactive sphingolipid sphingosine 1-phosphate (S1P) elicits robust
      cytoskeletal rearrangement in a large variety of cell systems, mainly acting
      through a panel of specific cell surface receptors, named S1P receptors. Recent
      studies have begun to delineate the molecular mechanisms involved in the complex
      process responsible for cytoskeletal rearrangement following S1P ligation to its
      receptors. Notably, changes of cell shape and/or motility induced by S1P via
      cytoskeletal remodelling are functional to the biological action exerted by S1P
      which appears to be highly cell-specific. This review focuses on the current
      knowledge of the regulatory mechanisms of cytoskeleton dynamics elicited by S1P,
      with special emphasis on the relationship between cytoskeletal remodelling and
      the biological effects evoked by the sphingolipid in various cell types.

PMID- 16890188
TI  - Blushing during social interactions in people with a fear of blushing.
AB  - Changes in facial blood flow were investigated during an introductory
      conversation, delivering a speech, and listening to the speech afterwards in 16
      people with a fear of blushing and 16 controls. It was hypothesized that fear of
      blushing would be associated with high ratings of self-reported blushing
      intensity and embarrassment during the tasks, and with persistence of the
      blushing reaction between tasks. Embarrassment and self-reported blushing
      intensity were greater in the fear-of-blushing group than in controls throughout
      the experiment. Increases in facial blood flow were similar in the two groups
      during each of the tasks. However, blushing dissipated more slowly after each
      task in the fear-of-blushing group than in controls, resulting in an incremental
      increase in facial blood flow over the course of the experiment. The slow
      recovery after an episode of blushing might result in physiological or social
      cues that help to maintain a fear of blushing.

PMID- 16890189
TI  - Correlation between the expression level of c-maf and glutathione peroxidase-3 in
      c-maf -/- mice kidney and c-maf overexpressed renal tubular cells.
AB  - Large mafs are transcriptional factors and members of the basic leucine zipper (b
      Zip) superfamily. Since we previously identified expression of c-maf in mouse
      kidney, we presently investigated the mRNA expression profile in the kidney of c
      maf gene knockout mice by using DNA microarray, and plasma glutathione peroxidase
      3 (GPx3) was predominantly downregulated. We focused on the relation between the
      expression level of c-maf and GPx3 in vivo and in vitro. Since GPx3 is an
      antioxidant enzyme, oxidative stress was induced by exposing a culture cell
      derived from mouse renal tubules (mIMCD3) to hydrogen peroxide. Real-time PCR
      demonstrated that mRNA expression of both c-maf and GPx3 increased in parallel
      during exposure to oxidative stress in a time- and dose-dependent manner. Then,
      the mIMCD3 cells were transfected with c-maf-cDNA containing plasmid, which
      resulted in an increase in mRNA and protein expression of GPx3 compared with the
      control cells. Thus, c-maf may be transcriptional regulator of GPx3 expression
      and modulate the antioxidative pathway in the kidney.

PMID- 16890190
TI  - Aberrantly regulated proteins in frontotemporal dementia.
AB  - Non-Alzheimer's disease of the frontal type, or frontotemporal dementia (FTD), is
      the second most common form of dementia. Yet, a detailed characterization of the
      disease has been especially limiting. To identify mechanisms possibly involved in
      disease pathology or progression, a proteomic analysis of proteins isolated from
      human frontal cortex with frontotemporal dementia and parkinsonism linked to
      chromosome 17 (FTDP-17) was performed. We used 2D gel electrophoresis and MALDI
      TOF to identify a total of 24 proteins differentially expressed in FTDP-17. We
      identified a ubiquitin C-terminal hydrolase, UCHL1, as well as several proteins
      involved in oxidative stress to be differentially expressed. Data presented
      implicate UCHL1 and ubiquitin-mediated degradation as well as oxidative stress
      response in disease pathology or progression.

PMID- 16890191
TI  - Gating defects of a novel Na+ channel mutant causing hypokalemic periodic
      paralysis.
AB  - Hypokalemic periodic paralysis type 2 (hypoPP2) is an inherited skeletal muscle
      disorder caused by missense mutations in the SCN4A gene encoding the alpha
      subunit of the skeletal muscle Na+ channel (Nav1.4). All hypoPP2 mutations
      reported so far target an arginine residue of the voltage sensor S4 of domain II
      (R672/G/H/S). We identified a novel hypoPP2 mutation that neutralizes an arginine
      residue in DIII-S4 (R1132Q), and studied its functional consequences in HEK cells
      transfected with the human SCN4A cDNA. Whole-cell current recordings revealed an
      enhancement of both fast and slow inactivation, as well as a depolarizing shift
      of the activation curve. The unitary Na+ conductance remained normal in R1132Q
      and in R672S mutants, and cannot therefore account for the reduction of Na+
      current presumed in hypoPP2. Altogether, our results provide a clear evidence for
      the role of R1132 in channel activation and inactivation, and confirm loss of
      function effects of hypoPP2 mutations leading to muscle hypoexcitability.

PMID- 16890192
TI  - Berberine inhibits 3T3-L1 adipocyte differentiation through the PPARgamma
      pathway.
AB  - Berberine (BBR), a compound purified from Cortidis rhizoma, reduces serum
      cholesterol, triglycerides, and LDL-cholesterol of hypercholesterolemic patients
      and high fat diet fed animals, and increases hepatic LDLR mRNA and protein levels
      through a post-transcriptional mechanism. BBR also enhances the hypoglycemic
      action of insulin in diabetic animal models. Here, we show that BBR inhibits the
      differentiation of 3T3-L1 preadipocytes induced by DM and suppresses the mitotic
      clonal expansion of 3T3-L1 preadipocytes in a time- and dose-dependent manner.
      Gene expression analysis and Western blot analysis reveal that the BBR inhibits
      the mRNA and protein levels of adipogenesis related transcription factors
      PPARgamma and C/EBPalpha and their upstream regulator, C/EBPbeta. Reporter gene
      assays demonstrate that the full-length PPARgamma and alpha transcription
      activities are inhibited by BBR. Using real-time PCR, we have also found that the
      PPAR target genes that are involved in adipocyte differentiation, such as aP2,
      CD36, ACO, LPL, and other adipocyte markers, are suppressed by BBR. These studies
      suggest that BBR works on multiple molecular targets as an inhibitor of PPARgamma
      and alpha, and is a potential weight reducing, hypolipidemic, and hypoglycemic
      drug.

PMID- 16890193
TI  - Blocking c-myc and stat3 by E. coli expressed and enzyme digested siRNA in mouse
      melanoma.
AB  - Tumour cells often show alteration in the signal-transduction pathways, leading
      to proliferation in response to external signals. Oncogene overexpression and
      constitutive expression is a common phenomenon in the development and progression
      of many human cancers. Therefore oncogenes provide potential targets for cancer
      therapy. RNA interference (RNAi), mediated by small interfering RNA (siRNA),
      silences genes with a high degree of specificity and potentially represents a
      general approach for molecularly targeted anti-cancer therapy. The data presented
      in this report evaluated the method of systemically administering combined
      esiRNAs to multiple targets as compared with the method of using a single kind of
      esiRNA to a single target. Our experimental data revealed that the mixed
      treatment of esiC-MYC and esiSTAT3 had a better inhibition effect than the single
      treatment of esiC-MYC or esiSTAT3 on mouse B16 melanoma.

PMID- 16890194
TI  - Breast carcinoma specific antibody selection combining phage display and
      immunomagnetic cell sorting.
AB  - To discover new specific antibodies directed against disseminated carcinoma cells
      in breast cancer patients, a strategy combining single-chain variable fragment
      (scFv) phage display and immunomagnetic cell sorting was developed. A selection
      model, in which ErbB2-expressing breast carcinoma SKBR3 cells are spiked into a
      50-fold excess of lymphocytes, was setup. Selection conditions, optimized using
      the previously characterized ErbB2-specific F5 phage scFv, led to an outstanding
      phage enrichment yield of 25,000 after only one round. This protocol applied to
      human nai ve and synthetic phage display antibody libraries led to the selection,
      in only two rounds, of individual scFv clones (43 out of 46 tested) specific for
      non-epithelial carcinoma antigens expressed on SKBR3 cells. This strategy is
      fully applicable to metastatic cells in effusions from breast carcinoma patients
      and shall lead to the discovery of immunotools crucial for novel diagnostic and
      therapeutic approaches.

PMID- 16890195
TI  - Ets transcription factors regulate AIRE gene promoter.
AB  - Autoimmune regulator (AIRE) directs the expression of self-antigens in thymus.
      Defects in AIRE gene cause an organ-specific autoimmune disease called autoimmune
      polyendocrinopathy candidiasis ectodermal dystrophy (APECED). AIRE protein is
      mainly expressed in thymic medullary epithelial cells, thus implying a strict
      control over its expression pattern. To date, only limited information is
      available on mechanisms responsible for the regulation of AIRE gene. Here, we
      show that Ets transcription factor family members Ets-1, Ets-2, and ESE-1 have
      positive effect on AIRE transcription. Site-directed mutagenesis and transfection
      studies revealed that two of the three Ets binding sites in AIRE promoter are
      functional and this finding has been confirmed by the electrophoretic mobility
      shift assay. The AIRE promoter activity could be stimulated by phorbol myristate
      acetate (PMA) and this activation was further enhanced by Ets transcription
      factors. Our results demonstrate for the first time that AIRE gene is a
      downstream target for the Ets family of transcription factors.

PMID- 16890196
TI  - Molecular insights of the injured lesions of rat spinal cords: Inflammation,
      apoptosis, and cell survival.
AB  - Spinal cord injury (SCI) is a devastating neurologic injury with functional
      deficits. In the acute phase, which starts at the moment of the injury and
      extends over the first few days, numerous pathological processes begin. In this
      study, we made several additional advances to broaden our understanding of SCI
      induced gene expression changes. We examined changes at multiple time points: 0,
      6, 24, 48, and 72 h after injury, with the latter time period being added. Also,
      we utilized multiple analysis methods such as real-time RT-PCR, Western blot, and
      immunohistochemistry to increase confidence in our candidate gene and molecular
      processes. From the pool of information, we generated profiles of expression
      changes and molecular mechanisms of several injury processing. Early stages after
      the injury are characterized by the strong upregulation of genes involved in
      transcription, inflammation, and signaling proteins, and a general downregulation
      of neural function-related genes. In addition, edema of the spinal cord develops,
      and metabolic disturbances involving intra-neuronal Ca2+ accumulation occur. This
      translates into a general failure of normal neural functions and a stage of
      signal shock that lasts for a few days in experimental rat models. Traumatic
      injury to the spinal cord also leads to a strong inflammatory response with the
      recruitment of peripherally derived immature cells, such as ED1-positive
      macrophages. After the trauma, apoptotic cell death continues, and scarring and
      demyelination accompany Wallerian degeneration. Strong expression of
      transcription factors of the Janus-activated kinase (JAK) and signal transducer
      and activator of transcription (STAT) family represents an early attempt of
      spinal cord repair and regeneration. Our study allowed us to conclude that
      combined therapeutic strategies for enhanced recovery should be performed until
      the chronic phase of the injury in areas distal to the lesion epicenter of spinal
      cords.

PMID- 16890197
TI  - Fast and sensitive DNA hybridization assays using microwave-accelerated metal
      enhanced fluorescence.
AB  - A new, fast, and sensitive DNA hybridization assay platform based on microwave
      accelerated metal-enhanced fluorescence (MAMEF) is presented. Thiolated
      oligonucleotide anchors were immobilized onto silver nanoparticles on a glass
      substrate. The hybridization of the complementary fluorescein-labeled DNA target
      with the surface-bound oligonucleotides was completed within 20 s upon heating
      with low-power microwaves. In addition, the signal is optically amplified, a
      consequence of close proximity of the fluorophore to the silvered substrate. In
      this proof-of-principle methodology, as low as 50 nM of a target DNA was
      detected, although we envisage far-lower detection limits. Control experiments,
      where the surface-bound oligonucleotide was omitted, were also performed to
      determine the extent of non-specific binding. In these studies a significantly
      reduced non-specific adsorption was found when using microwave heating near to
      silvered structures as compared to room temperature incubation. These findings
      suggest that MAMEF could be a most useful alternative to the DNA hybridization
      assays used today, especially with regard to substantially increasing both the
      assay rapidity and sensitivity.

PMID- 16890199
TI  - Control of the ATP synthase beta subunit expression by RNA-binding proteins TIA
      1, TIAR, and HuR.
AB  - The beta-subunit of the mitochondrial H+-ATP synthase (beta-F1-ATPase) catalyzes
      the rate-limiting step of ATP formation in eukaryotic cells. Here, we examined
      the post-transcriptional regulation of human beta-F1-ATPase mediated by the 3'
      untranslated region of the mRNA (beta-3'-UTR). Biochemical analysis revealed that
      the adenosine/uridine (AU)-rich element-binding proteins TIA-1 (T-cell
      intracellular antigen-1), TIAR (TIA-1-related protein), and HuR (Hu antigen R)
      interact with the beta-F1-ATPase mRNA through an AU-rich sequence located to the
      3'-UTR. Mouse embryonic fibroblasts (MEFs) knocked-out for TIA-1 or RNA
      interference (RNAi)-mediated knockdown of endogenous TIA-1, TIAR, or HuR in HeLa
      cells resulted in a decrease in beta-F1-ATPase protein expression. The expression
      of GFP from a chimeric reporter containing human beta-3'-UTR was also abolished
      in HeLa cells depleted of TIA-1, TIAR, or HuR. MEFs knocked-in for TIA-1 or the
      overexpression of RNAi-resistant TIA-1, TIAR, or HuR proteins in the RNAi-treated
      HeLa cells significantly restored the levels of the expression of both endogenous
      mouse beta-F1-ATPase protein or recombinant GFP.

PMID- 16890198
TI  - Aurelin, a novel antimicrobial peptide from jellyfish Aurelia aurita with
      structural features of defensins and channel-blocking toxins.
AB  - A novel 40-residue antimicrobial peptide, aurelin, exhibiting activity against
      Gram-positive and Gram-negative bacteria, was purified from the mesoglea of a
      scyphoid jellyfish Aurelia aurita by preparative gel electrophoresis and RP-HPLC.
      Molecular mass (4296.95 Da) and complete amino acid sequence of aurelin
      (AACSDRAHGHICESFKSFCKDSGRNGVKLRANCKKTCGLC) were determined. Aurelin has six
      cysteines forming three disulfide bonds. The total RNA was isolated from the
      jellyfish mesoglea, RT-PCR and cloning were performed, and cDNA was sequenced. A
      84-residue preproaurelin contains a putative signal peptide (22 amino acids) and
      a propiece of the same size (22 amino acids). Aurelin has no structural homology
      with any previously identified antimicrobial peptides but reveals partial
      similarity both with defensins and K+ channel-blocking toxins of sea anemones and
      belongs to ShKT domain family.

PMID- 16890200
TI  - A novel redox-based switch: LMW-PTP oxidation enhances Grb2 binding and leads to
      ERK activation.
AB  - Low molecular weight-PTP has been reported as a redox-sensitive protein during
      both platelet-derived growth factor and integrin signalling. In response to
      oxidation the phosphatase undergoes a reversible inactivation, which in turn
      leads to the increase in tyrosine phosphorylation of its substrates and the
      properly executed anchorage-dependent proliferation program. Here, we report that
      an exogenous oxidative stress enhances LMW-PTP tyrosine phosphorylation, through
      oxidation/inactivation of the enzyme, thus preventing its auto-dephosphorylation
      activity. In particular, we observed a selective hyper-phosphorylation of Tyr132,
      that acts as a docking site for the adaptor protein Grb2. The redox-dependent
      enhancement of Grb2 recruitment to LMW-PTP ultimately leads to an improvement of
      ERK activation, likely triggering a prosurvival signal against the oxidant
      environment.

PMID- 16890201
TI  - Suppression of anchorage-independent growth by expression of the ataxia
      telangiectasia group D complementing gene, ATDC.
AB  - The ataxia-telangiectasia group D complementing gene, ATDC, is located at 11q23,
      where loss of heterozygosity (LOH) is frequently observed in many kinds of
      cancers including breast cancer. Underexpression of ATDC in breast and prostate
      cancer has been reported using serial analysis of gene expression (SAGE) and DNA
      microarray analysis. We previously reported that SV-40-transformation down
      regulates the expression of ATDC. In the present study, we investigated the roles
      of ATDC in carcinogenesis. First, we investigated the expression of ATDC in 11
      cancer cell lines. No detectable transcript was observed in 4 tumor cell lines,
      and no ATDC protein was detected in 8 tumor cell lines. We transfected ATDC
      expression vector into Saos-2 and BT-549 that lacked detectable mRNA and protein
      expression of ATDC. Colony-forming efficiency in soft agar was significantly
      suppressed in all of the ATDC transfectants. These results suggest that
      suppressed ATDC expression is associated with malignant phenotype.

PMID- 16890202
TI  - Salvianolic acid B, an antioxidant from Salvia miltiorrhiza, prevents Abeta(25
      35)-induced reduction in BPRP in PC12 cells.
AB  - Several lines of evidence support that beta-amyloid (Abeta)-induced neurotoxicity
      is mediated through the generation of reactive oxygen species (ROS) and elevation
      of intracellular calcium. Salvianolic acid B (Sal B), the major and most active
      anti-oxidant from Salvia miltiorrhiza, protects diverse kinds of cells from
      damage caused by a variety of toxic stimuli. In the present study, we
      investigated the effects of Sal B against beta-amyloid peptide 25-35 (Abeta(25
      35))-induced neurotoxicity, focused mainly on the neurotoxic effects of Abeta(25
      35) and the neuroprotective effects of Sal B on the expression of brain-pancreas
      relative protein (BPRP), which is a new protein and mainly expressed in brain and
      pancreas. Following exposure of PC12 cells to 20 microM Abeta(25-35), a marked
      reduction in the expression of BPRP was observed, accompanied with decreased cell
      viability and increased cell apoptosis, as well as increased ROS production and
      calcium influx. Treatment of the PC12 cells with Sal B significantly reversed the
      expression of BPRP and cell viability while it decreased ROS production and
      intracellular calcium. These data indicate that Abeta(25-35) decreases the
      expression of BPRP via enhanced formation of intracellular ROS and increased
      intracellular calcium, and that Sal B, as an anti-oxidant, protects against
      Abeta(25-35)-induced reduction in expression of BPRP through its effects on
      suppressing the production of ROS, calcium flux, and apoptosis. However, the
      role(s) of BPRP in AD and the definite mechanisms by which Sal B protects against
      Abeta(25-35)-induced reduction in the expression of BPRP require further study.

PMID- 16890203
TI  - Inhibition of the TPA-induced cutaneous inflammation and hyperplasia by EC-SOD.
AB  - This study reports the roles of extracellular superoxide dismutase (EC-SOD) in
      the cutaneous inflammation and hyperplasia with 12-O-tetradecanoylphorbol-3
      acetate (TPA) application in EC-SOD transgenic mice (Tg EC-SOD). Topical double
      TPA treatment induced the various inflammatory changes including the epidermal
      thickness, elevated the PCNA-labeling index, the edema formation, and increased
      production of hydrogen peroxide (H2O2) in wild type mice (WT). These changes were
      markedly suppressed in TPA-treated Tg EC-SOD. The expressions of the inflammatory
      cytokines, IL-1alpha and IL-1beta, were reduced in the TPA-treated Tg EC-SOD
      compared with those in TPA-treated WT. The expression of IL-1alpha was
      significantly increased in the skin of TPA-treated WT, especially in the basal
      and suprabasal layers, but it was restricted focally in basal layer of the skin
      of TPA-treated Tg EC-SOD. The number of infiltrating inflammatory cells and the
      IL-1beta expressing cells was obviously reduced in TPA-treated Tg EC-SOD in
      comparison with TPA-treated WT. The result suggests that EC-SOD might play an
      important role in the suppression of TPA-induced cutaneous inflammation and
      epidermal hyperplasia by regulating the expression of IL-1alpha and IL-1beta,
      although the mechanisms remain to be elucidated.

PMID- 16890204
TI  - Genetic variations of the NR3C1 gene in children with sporadic nephrotic
      syndrome.
AB  - Previous studies have demonstrated that the genetic variations of glucocorticoid
      receptor gene (NR3C1) are associated with both familial steroid resistance and
      acquired steroid resistance in some diseases, such as Cushing's disease,
      leukemia, lupus nephritis, and female pseudohermaphroditism. In this study, we
      examined the genetic variations of NR3C1 in 35 children with sporadic steroid
      resistant nephrotic syndrome (SRNS), and in 83 cases with sporadic steroid
      sensitive NS (SSNS) using polymerase chain reaction, denaturing high-performance
      liquid chromatography and DNA sequencing, and analyzed possible associations
      between NR3C1 variants and steroid resistance in sporadic NS. No causative
      mutations were found; however, six previously identified and six novel
      polymorphisms, 1206C > T, 1374A > G, 2382C > T, 2193T > G, IVS7-68_-63delAAAAAA,
      and IVS8-9C > G, were detected. Two novel haplotypes, [1374A > G; IVS7-68_
      63delAAAAAA; IVS8-9C > G; 2382C > T] and [1896C > T; 2166C > T; 2430T > C], of
      NR3C1 were also identified in sporadic NS and controls. The odds ratios (95%
      Confidence Interval) for the two novel NR3C1 haplotypes in the sporadic nephrotic
      children at risk of steroid resistance were 4.970 (0.889-27.788) and 2.194 (0.764
      6.306), respectively, but the association between NR3C1 haplotypes and steroid
      resistance was not significant. Further studies on the possible association
      between the two novel NR3C1 haplotypes and steroid resistance in sporadic NS in
      larger cohorts are required.

PMID- 16890205
TI  - Biophysical characterisation of electrofused giant HEK293-cells as a novel
      electrophysiological expression system.
AB  - Giant HEK293 cells of 30-65 microm in diameter were produced by three-dimensional
      multi-cell electrofusion in 75 mOsm sorbitol media. These strong hypotonic
      conditions facilitated fusion because of the spherical shape and smooth membrane
      surface of the swollen cells. A regulatory volume decrease (RVD), as observed at
      higher osmolalities, did not occur at 75 mOsm. In contrast to field-treated, but
      unfused cells, the increase in volume induced by hypotonic shock was only partly
      reversible in the case of fused giant cells after their transfer into isotonic
      medium. The large size of the electrofused cells allowed the study of their
      electrophysiological properties by application of both whole-cell and giant
      excised patch-clamp techniques. Recordings on giant cells yielded a value of
      1.1+/-0.1 microF/cm2 for the area-specific membrane capacitance. This value was
      consistent with that of the parental cells. The area-specific conductivity of
      giant cells (diameter > 50 microm) was found to be between 12.8 and 16.1
      microS/cm2, which is in the range of that of the parental cells. Measurements
      with patch-pipettes containing fluorescein showed uniform dye uptake in the whole
      cell configuration, but not in the cell-attached configuration. The diffusion
      controlled uniform uptake of the dye into the cell interior excludes internal
      compartmentalisation. The finding of a homogeneous fusion was also supported by
      expression of the yellow fluorescent protein YFP (as part of the fusion-protein
      ChR2-YFP) in giant cells since no plasma-membrane bound YFP-mediated fluorescence
      was detected in the interior of the electrofused cells. Functional expression and
      the electrophysiological characterisation of the light-activated cation channel
      Channelrhodopsin 2 (ChR2) yielded similar results as for parental cells. Most
      importantly, the giant cells exhibited a comparable expression density of the
      channel protein in the plasma membrane as observed in parental cells. This
      demonstrates that electrofused cells can be used as a heterologous expression
      system.

PMID- 16890206
TI  - Interactions of ribosomal protein S1 with DsrA and rpoS mRNA.
AB  - Ribosomal protein S1 is shown to interact with the non-coding RNA DsrA and with
      rpoS mRNA. DsrA is a non-coding RNA that is important in controlling expression
      of the rpoS gene product in Escherichia coli. Photochemical crosslinking,
      quadrupole-time of flight tandem mass spectrometry, and peptide sequencing have
      identified an interaction between DsrA and S1 in the 30S ribosomal subunit.
      Purified S1 binds both DsrA (K(obs) approximately 6 x 10(6) M(-1)) and rpoS mRNA
      (K(obs) approximately 3 x 10(7) M(-1)). Ribonuclease probing experiments indicate
      that S1 binding has a weak but detectable effect on the secondary structure of
      DsrA or rpoS mRNA.

PMID- 16890207
TI  - Action of diclofenac on kidney mitochondria and cells.
AB  - The mitochondrial membrane potential measured in isolated rat kidney mitochondria
      and in digitonin-permeabilized MDCK type II cells pre-energized with succinate,
      glutamate, and/or malate was reduced by micromolar diclofenac dose-dependently.
      However, ATP biosynthesis from glutamate/malate was significantly more
      compromised compared to that from succinate. Inhibition of the malate-aspartate
      shuttle by diclofenac with a resultant decrease in the ability of mitochondria to
      generate NAD(P)H was demonstrated. Diclofenac however had no effect on the
      activities of NADH dehydrogenase, glutamate dehydrogenase, and malate
      dehydrogenase. In conclusion, decreased NAD(P)H production due to an inhibition
      of the entry of malate and glutamate via the malate-aspartate shuttle explained
      the more pronounced decreased rate of ATP biosynthesis from glutamate and malate
      by diclofenac. This drug, therefore affects the bioavailability of two major
      respiratory complex I substrates which would normally contribute substantially to
      supplying the reducing equivalents for mitochondrial electron transport for
      generation of ATP in the renal cell.

PMID- 16890208
TI  - Mitogenic and drug-resistance mediating effects of PKCalpha require RLIP76.
AB  - PKCalpha-activation is a key signaling event governing cell growth, stress
      resistance, and drug-resistance. Our recent studies demonstrated that DOX
      resistance mediating effects of PKCalpha require the presence of RLIP76, and
      their concerted action is sufficient to explain intrinsic DOX-resistance of NSCLC
      [S.S. Singhal, D. Wickramarachchi, J. Singhal, S. Yadav, Y.C. Awasthi, et al.,
      Determinants of differential doxorubicin sensitivity between SCLC and NSCLC. FEBS
      Lett. 580 (2006) 2258-2264]. Present studies were carried out to further explore
      the suggestion from the previous studies that the mitogenic effects of PKCalpha
      also require RLIP76. RLIP76-/- MEFs were resistant to PKCalpha-depletion mediated
      growth inhibition, as well as to the PKCalpha-dependent mitogen, phorbol 12
      myristate 13-acetate (PMA). Augmenting cellular levels of RLIP76 using purified
      recombinant RLIP76 increased growth rate in all cells, and restored the
      sensitivity of RLIP76-/- MEFs to both inhibition through PKCalpha-depletion and
      stimulation through PMA. These results show that RLIP76 is a necessary down
      stream effector for PKCalpha-mediated mitogenesis.

PMID- 16890209
TI  - Suppression of MyD88- and TRIF-dependent signaling pathways of Toll-like receptor
      by (-)-epigallocatechin-3-gallate, a polyphenol component of green tea.
AB  - Toll-like receptors (TLRs) play an important role in recognition of microbial
      components and induction of innate immunity. The microbial components trigger the
      activation of two downstream signaling pathways of TLRs; MyD88- and/or TRIF
      dependent pathways leading to activation of NF-kappaB. (-)-Epigallocatechin-3
      gallate (EGCG), a flavonoid found in green tea, is known to inhibit NF-kappaB
      activation induced by many pro-inflammatory stimuli. EGCG was shown to inhibit
      the activity of IKKbeta which is the key kinase in the canonical pathway for NF
      kappaB activation in MyD88-dependent pathway of TLRs. However, it is not known
      whether EGCG inhibits TRIF-dependent pathway through which more than 70% of
      lipopolysaccharide (LPS)-induced genes are regulated. Therefore, we attempted to
      identify the molecular target of EGCG in TRIF-dependent pathways of TLR3 and
      TLR4. EGCG inhibited the activation of IFN regulatory factor 3 (IRF3) induced by
      LPS, poly[I:C], or the overexpression of TRIF. The inhibition of IRF3 activation
      by EGCG was mediated through the suppression of the kinase activity of TBK1.
      However, EGCG did not inhibit activation of IRF3 induced by overexpression of
      constitutively active IRF3. These results suggest that the molecular target of
      EGCG is TBK1 in TRIF-dependent signaling pathways of TLR3 and TLR4. Therefore,
      our results suggest that green tea flavonoids can modulate both MyD88- and TRIF
      dependent signaling pathways of TLRs and subsequent inflammatory target gene
      expression.

PMID- 16890210
TI  - Neuroanatomical localization of an internal clock: a functional link between
      mesolimbic, nigrostriatal, and mesocortical dopaminergic systems.
AB  - The effects of selective dopamine (DA) depleting lesions with 6-hydroxydopamine
      microinjection into the SN, CPu, and NAS, as well as radiofrequency lesions of
      the CPu on the performance characteristics of rats trained on a single-valued 20
      s peak-interval (PI) timing procedure or a double-valued 10-s and 60-s PI
      procedure were evaluated. A double dissociation in the performance of duration
      discriminations was found. Rats with CPu lesions were unable to exhibit temporal
      control of their behavior suggesting complete insensitivity to signal duration
      but were able to show discrimination of the relative reward value of a signal by
      differentially modifying their response rates appropriately. In contrast, rats
      with NAS lesions were able to exhibit temporal control of their behavior by
      differentially modifying their response rates as a function of signal
      duration(s), suggesting no impairment of sensitivity to signal duration, but were
      unable to show discrimination of the relative reward value of a signal.

PMID- 16890211
TI  - Antioxidant actions contribute to the antihypertrophic effects of atrial
      natriuretic peptide in neonatal rat cardiomyocytes.
AB  - OBJECTIVE: Reactive oxygen species (ROS) such as superoxide have been linked to
      the hypertrophic response of the heart to stimuli including angiotensin II
      (AngII), mechanical stretch, and pressure overload. We have previously
      demonstrated that cGMP and protein kinase G mediate the antihypertrophic actions
      of the natriuretic peptides in rat cardiomyocytes and isolated whole hearts. The
      impact of natriuretic peptides on cardiac ROS generation, however, has not been
      investigated. We tested the hypothesis that reduced superoxide accumulation
      contributes to the antihypertrophic action of atrial natriuretic peptide (ANP).
      METHODS: Neonatal rat cardiomyocytes were cultured in serum-free medium with and
      without AngII (1 micromol/L) or endothelin-1 (ET(1), 60 nmol/L) in the presence
      and absence of ANP (1 micromol/L) or tempol (100 micromol/L). Hypertrophic
      responses, cardiomyocyte superoxide generation, and cardiomyocyte expression of
      NADPH oxidase were determined. RESULTS: AngII induced increases in cardiomyocyte
      size (to 176 +/- 9% n = 8 p < 0.001, at 48 h), beta-myosin heavy chain expression
      (to 4.0 +/- 1.6-fold n = 6 p < 0.05, at 48 h), c-fos expression (to 1.9 +/- 0.5
      fold n = 7 p < 0.01, at 6 h), superoxide generation (to 181+/-21% n = 8 p <
      0.005, at 24 h), and expression of the gp91phox subunit of NADPH oxidase (to 2.4
      +/- 0.5-fold n = 7 p < 0.05, at 48 h). These effects were all significantly
      inhibited by ANP: cardiomyocyte size, beta-myosin heavy chain expression, c-fos
      expression, superoxide generation and gp91phox expression were reduced to 107 +/-
      5% (n = 5 p < 0.05), 1.2 +/- 0.2-fold (n = 6 p < 0.05), 0.9 +/- 0.2-fold (n = 7 p
      < 0.05), 141 +/- 21% (n = 8 p < 0.05), and to 1.0 +/- 0.5-fold (n = 7 p < 0.05),
      respectively. These effects were mimicked by tempol. ANP and tempol also
      significantly inhibited ET1-induced increases in cardiomyocyte size and
      superoxide generation, but had no effect on markers of hypertrophy when studied
      alone. CONCLUSION: This data indicates that the antihypertrophic actions of ANP
      are accompanied by reduced levels of superoxide, suggesting an antioxidant action
      contributes to the antihypertrophic actions of ANP.

PMID- 16890212
TI  - Multi-component analysis of marine lipids in fish gonads with emphasis on
      phospholipids using high resolution NMR spectroscopy.
AB  - High resolution NMR has been applied for assessment of lipid classes and acyl
      stereospecific positions of fatty acids in marine phospholipids and
      triacylglycerols. 1D and 2D NMR techniques in combination with recording of a
      number of reference standards have been used to interpret the (1)H and (13)C NMR
      spectra of fish gonads. (13)C NMR spectra gave information regarding the
      polyunsaturated fatty acids (PUFAs) in phosphatidylcholine (PC) and
      phosphatidylethanolamine (PE). The carbonyl resonances showed that n-3 PUFAs
      primarily were esterified in the sn-2 position of PC and PE. The glycerol
      resonances showed that the PC/PE ratio was higher in roe than in milt and that
      roe comprised more triacylglycerols than milt. Thin layer chromatography showed
      that milt contained 2.4 times more cholesterol than roe, which was also found by
      integrating the (1)H NMR spectra. Concentration (mol%) of n-3 fatty acids were
      calculated from the (1)H NMR data and showed 44.8 and 36.3% in roe and milt,
      respectively.

PMID- 16890213
TI  - Roots, stems, and the universality of lexical representations: evidence from
      Hebrew.
AB  - Is the structure of lexical representations universal, or do languages vary in
      the fundamental ways in which they represent lexical information? Here, we
      consider a touchstone case: whether Semitic languages require a special morpheme,
      the consonantal root. In so doing, we explore a well-known constraint on the
      location of identical consonants that has often been used as motivation for root
      representations in Semitic languages: Identical consonants frequently occur at
      the end of putative roots (e.g., skk), but rarely occur in their beginning (e.g.,
      ssk). Although this restriction has traditionally been stated over roots, an
      alternative account could be stated over stems, a representational entity that is
      found more widely across the world's languages. To test this possibility, we
      investigate the acceptability of a single set of roots, manifesting identity
      initially, finally or not at all (e.g., ssk versus skk versus rmk) across two
      nominal paradigms: CeCeC (a paradigm in which identical consonants are rare) and
      CiCuC (a paradigm in which identical consonants are frequent). If Semitic lexical
      representations consist of roots only, then similar restrictions on consonant co
      occurrence should be observed in the two paradigms. Conversely, if speakers store
      stems, then the restriction on consonant co-occurrence might be modulated by the
      properties of the nominal paradigm (be it by means of statistical properties or
      their grammatical sources). Findings from rating and lexical decision experiments
      with both visual and auditory stimuli support the stem hypothesis: compared to
      controls (e.g., rmk), forms with identical consonants (e.g., ssk, skk) are less
      acceptable in the CeCeC than in the CiCuC paradigm. Although our results do not
      falsify root-based accounts, they strongly raise the possibility that stems could
      account for the observed restriction on consonantal identity. As such, our
      results raise fresh challenge to the notion that different languages require
      distinct sets of representational resources.

PMID- 16890214
TI  - Modeling response signal and response time data.
AB  - The diffusion model (Ratcliff, 1978) and the leaky competing accumulator model
      (LCA, Usher & McClelland, 2001) were tested against two-choice data collected
      from the same subjects with the standard response time procedure and the response
      signal procedure. In the response signal procedure, a stimulus is presented and
      then, at one of a number of experimenter-determined times, a signal to respond is
      presented. The models were fit to the data from the two procedures simultaneously
      under the assumption that responses in the response signal procedure were based
      on a mixture of decision processes that had already terminated at response
      boundaries before the signal and decision processes that had not yet terminated.
      In the latter case, decisions were based on partial information in one variant of
      each model or on guessing in a second variant. Both variants of the diffusion
      model fit the data well and both fit better than either variant of the LCA model,
      although the differences in numerical goodness-of-fit measures were not large
      enough to allow decisive selection between the models.

PMID- 16890215
TI  - Numerical analysis of forced injection of enzyme during thrombolysis.
AB  - Numerical analysis was performed on the enzyme transport and the flow fields in
      order to predict the effectiveness of forced injection in thrombolytic therapy.
      The species and momentum transport equations were numerically solved for the case
      of uniform perfusion of enzyme into the fibrin clot, and the validity of our
      methods were verified. In order to predict the lysis efficiency of continuous and
      forced intermittent injections, enzyme perfusion and clot lysis were simulated
      for the different injection velocities and frequencies. Intermittent injection
      showed faster clot lysis compared to continuous perfusion, and lysis efficiency
      was increased as the injection velocity and period increased.

PMID- 16890216
TI  - SER-1, a Caenorhabditis elegans 5-HT2-like receptor, and a multi-PDZ domain
      containing protein (MPZ-1) interact in vulval muscle to facilitate serotonin
      stimulated egg-laying.
AB  - Serotonin (5-HT) stimulation of egg-laying in Caenorhabditis elegans is abolished
      in ser-1 (ok345) animals and is rescued by ser-1 expression in vulval muscle. A
      PDZ binding motif (ETFL) at the SER-1 C-terminus is not essential for rescue, but
      facilitates SER-1 signaling. SER-1 binds specifically to PDZ domain 10 of the
      multi-PDZ domain protein, MPZ-1, based on GST pulldown and co
      immunoprecipitation. mpz-1 is expressed in about 60 neurons and body wall and
      vulval muscles. In neurons, GFP-tagged MPZ-1 is punctate and colocalizes with the
      synaptic marker, synaptobrevin. The expression patterns of ser-1 and mpz-1
      overlap in 3 pairs of neurons and vulval muscle. In addition, MPZ-1 also
      interacts with other GPCRs with acidic amino acids in the -3 position of their
      PDZ binding motifs. mpz-1 RNAi reduces 5-HT stimulated egg-laying in wild type
      animals and in ser-1 mutants rescued by muscle expression of SER-1. In contrast,
      mpz-1 RNAi has no effect on 5-HT stimulated egg-laying in ser-1 mutants rescued
      by expression of a truncated SER-1 that lacks the C-terminal PDZ binding motif.
      The overexpression of MPZ-1 PDZ domain 10 also inhibits 5-HT stimulated egg
      laying. These studies suggest that the SER-1/MPZ-1 interaction facilitates SER-1
      mediated signaling.

PMID- 16890217
TI  - Noggin1 and Follistatin-like2 function redundantly to Chordin to antagonize BMP
      activity.
AB  - In Xenopus, the dorso-ventral (D/V) axis is thought to be specified by the bone
      morphogenetic proteins (Bmp) activity arising through interaction with
      antagonists such as Noggin, Chordin and Follistatin. We report here, through
      inactivation of noggin1 (nog1) that this gene is not essential by itself to
      establish the D/V patterning. However, at blastula stage, inactivation of nog1
      strongly amplifies chordin (chd) phenotype, revealing redundant functions of
      these two genes on D/V axis formation. Substantial dorsal tissues remaining in
      the double nog1-chd morphant suggested that other anti-Bmp factors may pattern
      the D/V axis. We isolated two potential candidates, the follistatin-like (fstl)
      genes. We found that fstl2 is an early gastrula expressed gene. Its inactivation,
      similar to nog1, strongly enhances the chd phenotype. Moreover, the penetrance of
      the ventralization phenotype is much higher when we inactivated simultaneously
      chd, nog1 and fstl2. Altogether, our data reveal that, while Chordin is the main
      player of the D/V axis, sufficient to maintain proper activity of Bmp gradient,
      the structures remaining in the chd mutant (namely dorsal and dorso-lateral
      territories, in both mesodermal and ectodermal layers) result from the anti-Bmp
      activity carried by Nog1 and Fstl2 at blastula and gastrula stages.

PMID- 16890218
TI  - Total mercury levels in hair, toenail, and urine among women free from
      occupational exposure and their relations to renal tubular function.
AB  - To investigate the relations among total mercury levels in hair, toenail, and
      urine, together with potential effects of methylmercury intake on renal tubular
      function, we determined their levels, and urinary N-acetyl-beta-D-glucosaminidase
      activity (NAG) and alpha1-microglobulin (AMG) in 59 women free from occupational
      exposures, and estimated daily mercury intakes from fish and other seafood using
      a food frequency questionnaire. Mercury levels (mean+/-SD) in the women were
      1.51+/-0.91 microg/g in hair, 0.59+/-0.32 microg/g in toenail, and 0.86+/-0.66
      microg/g creatinine in urine; and, there were positive correlations among them
      (P<0.001). The daily mercury intake of 9.15+/-7.84 microg/day was significantly
      correlated with total mercury levels in hair, toenail, and urine (r=0.551, 0.537,
      and 0.604, P<0.001). Among the women, the NAG and AMG were positively correlated
      with both the daily mercury intake and mercury levels in hair, toenail, and urine
      (P<0.01); and, these relations were almost similar when using multiple regression
      analysis to adjust for possible confounders such as urinary cadmium (0.47+/-0.28
      microg/g creatinine) and smoking status. In conclusion, mercury resulting from
      fish consumption can explain total mercury levels in hair, toenail, and urine to
      some degree (about 30%), partly through the degradation into the inorganic form,
      and it may confound the renal tubular effect of other nephrotoxic agents. Also,
      the following equation may be applicable to the population neither with dental
      amalgam fillings nor with occupational exposures: [hair mercury
      (microg/g)]=2.44x[toenail mercury (microg/g)].

PMID- 16890220
TI  - Low levels of ambient air pollution during pregnancy and fetal growth among term
      neonates in Brisbane, Australia.
AB  - There is mounting evidence that maternal exposure to ambient air pollution during
      pregnancy is associated with adverse birth outcomes. We examined birth weight and
      small for gestational age (SGA <10th percentile for age and gender) among 26,617
      singleton full-term births in Brisbane, Australia (July 2000-June 2003), in
      relation to ambient pollution during pregnancy. We also examined head
      circumference (HC) and crown-heel length (CHL) among a sub-sample (n=21,432) of
      the term neonates. Maternal exposure to PM(10), visibility reducing particles
      (bsp), O(3) and NO(2) was assessed by calculating average exposure estimates over
      months and trimesters of pregnancy based on a citywide average of the pollutants.
      Linear and logistic regression models were employed to examine the effect of
      these pollutants on the birth outcomes after adjusting for potential confounders
      and season of birth. The regression coefficients were based on an inter-quartile
      range (IQR) increase in exposure as well as quartiles of exposure with the lowest
      used as a reference category. Trimester- and monthly specific exposures to all
      pollutants were not significantly associated with a reduction in either birth
      weight or HC, or an increased risk of SGA. An IQR increase in NO(2) during the
      third trimester was associated with a reduction in CHL (beta=-0.15cm, 95% CI 
      0.25 to -0.05cm) and this was concentrated around exposure during month nine. No
      other pollutants were associated with a reduction in CHL. In conclusion, there
      was no strong evidence suggesting that ambient air pollution during pregnancy is
      associated with sub-optimal fetal growth in Brisbane.

PMID- 16890219
TI  - General and specific mortality among the elderly during the 2003 heat wave in
      Genoa (Italy).
AB  - The effects of heat waves on health can be serious for elderly persons,
      especially those in urban areas. We investigated in-depth the mortality excess
      during the 2003 heat wave among elderly persons (>74 years) in the City of Genoa
      (Italy). The excess in general mortality was calculated for the period July 16
      August 31, as the ratio of observed to expected deaths. To evaluate "harvesting",
      we compared observed and expected mortality in the period September 2003-April
      2004. We also studied the relationship between mortality and climatic conditions
      considering daily maximum temperature and Humidex discomfort degrees, as well as
      "lag-time". For cause-specific mortality, we considered all pathologies reported
      on the death certificate. The excess in general mortality was significant and was
      greatest in the first half of August. During Summer 2003, in Genoa the climatic
      conditions (described in terms of maximum temperature and Humidex Index) were
      extremely hot; regarding lag-time, the greatest correlation between the number of
      observed deaths and the maximum temperature values was observed for the three
      preceding days (rho=0.568; significance level<0.01). The prominent causes of
      death, for which an excess was observed, were cerebrovascular diseases, severe
      respiratory diseases, severe renal diseases, dementia; moreover, certain
      pathologic conditions and symptoms, usually not lethal, were also frequent causes
      of death (e.g., hypovolemia, hyperpyrexia, decubitus ulcers and immobilization
      syndrome). The results of this study confirm the relationship between the heat
      waves and death among elderly, stressing that, because of their poorer physical
      health and the prevalence of cognitive disturbances that hinder risk perception,
      it is necessary to properly care for them during heat waves.

PMID- 16890221
TI  - Sexual dimorphic responses in wildlife exposed to endocrine disrupting chemicals.
AB  - Understanding the gender similarities and differences in how organisms respond
      following exposure to environmental chemicals is important if we are to determine
      the relative risk of these agents to wildlife and human populations. In this
      paper, we have chosen to focus on the sex determination and differentiation of
      fishes, amphibians, and reptiles, because of their close association with the
      environment and the number of environmental factors (e.g., temperature and
      endocrine disrupting chemicals) that are known to affect these phenomena in these
      taxa. We have discussed examples of gender differences in response to exposure to
      endocrine disrupting chemicals and found gender similarities about as often as we
      found differences. We found that most studies examined either one sex
      exclusively, or the experimental design did not include examining the effect of
      sex as a variable. Given the central role of sex steroid hormones in the sex
      determination and sexual differentiation of fishes, amphibians, and reptiles, we
      recommend that future research purposefully include sex as a factor, so that risk
      assessment by government agencies can address the probable gender differences in
      effects from exposure to chemicals in the environment.

PMID- 16890222
TI  - Human EML4, a novel member of the EMAP family, is essential for microtubule
      formation.
AB  - Human EML4 (EMAP-like protein 4) is a novel microtubule-associated WD-repeat
      protein of 120 kDa molecular weight, which is classified as belonging to the
      conserved family of EMAP-like proteins. Cosedimentation assays demonstrated that
      EML4 associates with in vitro polymerized microtubules. Correspondingly,
      immunofluorescence stainings and transient expression of EGFP-labeled EML4
      revealed a complete colocalization of EML4 with the interphase microtubule array
      of HeLa cells. We present evidence that the amino-terminal portion of EML4 (amino
      acids 1-249) is essential for the association with microtubules.
      Immunoprecipitation experiments revealed that EML4 is hyperphosphorylated on
      serine/threonine residues during mitosis. In addition, immunofluorescence
      stainings demonstrated that hyperphosphorylated EML4 is associated with the
      mitotic spindle, suggesting that the function of EML4 is regulated by
      phosphorylation. siRNA-mediated knockdown of EML4 in HeLa cells led to a
      significant decrease in the number of cells. In no case mitotic figures could be
      observed in EML4 negative HeLa cells. Additionally, we observed a significant
      reduction of the proliferation rate and the uptake of radioactive [3H]-thymidine
      as a result of EML4 silencing. Most importantly, EML4 negative cells showed a
      completely modified microtubule network, indicating that EML4 is necessary for
      correct microtubule formation.

PMID- 16890223
TI  - Local and distal responses to injury in the rapid functional recovery from spinal
      cord contusion in rat pups.
AB  - Young rats display an accelerated rate of locomotor recovery after contusive
      spinal cord injury (SCI) compared to adults subjected to a similar standardized
      injury. We examined possible differences in the responses to SCI at the injury
      site and in the distal cord that might contribute to this rapid recovery. P14-15
      rats were studied at 1, 3, 5, 7, and 28 days after injury at T8 produced with a
      weight drop device (10 g x 2.5 cm). We used immunohistochemistry to investigate
      distal plasticity of serotonergic and noradrenergic pathways that have been shown
      to modulate locomotion. After SCI, pups exhibited an expected decrease in
      monoaminergic innervation of the lumbosacral cord, consistent with partial loss
      of these descending pathways. Unlike published results for the adult, we found no
      evidence of partial reinnervation with time after injury. On the other hand,
      oligodendrocytes at and near the lesion epicenter of the young rats appeared
      unexpectedly resilient to the insult. No evidence of oligodendrocyte loss in
      spared white matter was detected at 24 h after injury, as compared to the 50%
      loss reported in adults. Rather, there was a significant increase in the density
      of oligodendrocytes by 5 days after injury that was associated with a dramatic
      upregulation of markers for glial progenitor cells after pup SCI. Our results
      suggest that an altered glial response near the injury epicenter as compared to
      that in adults is likely to contribute to the more rapid rate of recovery in
      hindlimb locomotor function in young rats after SCI.

PMID- 16890225
TI  - Elucidation of the beta-carotene hydroxylation pathway in Arabidopsis thaliana.
AB  - The first dedicated step in plant xanthophyll biosynthesis is carotenoid
      hydroxylation. In Arabidopsis thaliana, this reaction is performed by both heme
      (LUT1 and LUT5) and non-heme (CHY1 and CHY2) hydroxylases. No mutant completely
      abolishing alpha- or beta-carotene hydroxylation has been described to date. We
      constructed double and triple mutant combinations in CHY1, CHY2, LUT1, LUT5 and
      LUT2 (lycopene epsilon-cyclase). In chy1chy2lut2, 80% of leaf carotenoids is
      represented by beta-carotene. In chy1chy2lut5, beta-carotene hydroxylation is
      completely abolished, while hydroxylation of the beta-ring of alpha-carotene is
      still observed. The data are consistent with a role of LUT5 in beta-ring
      hydroxylation, and with the existence of an additional hydroxylase, acting on the
      beta-ring of alpha-, but not beta-carotene.

PMID- 16890224
TI  - Specific receptor subtype mediation of LPA-induced dual effects in cardiac
      fibroblasts.
AB  - Lysophosphatidic acid (LPA) is a phospholipid messenger with diverse effects
      mediated via receptors LPA1, LPA2 and LPA3. Our previous study revealed that
      serum LPA level is elevated after myocardial infarction (MI). However, very
      little is known about the effects of LPA on cardiac fibroblasts (CFs) that play a
      crucial role in left ventricular remodeling after MI. Here we demonstrated that
      LPA dose-dependently induced proliferation and collagen synthesis with the
      maximum stimulation at 10 microM that was preferentially mediated by LPA3. LPA
      also dose-dependently induced apoptotic cell death, as estimated by MTT assay,
      hoechst staining, TUNEL and flow cytometric analysis, with an IC(50) of 50
      microM. Moreover, apoptotic cell death may involve mitochondrial dysfunction and
      activation of caspase-3. Apoptosis induced by LPA might be mediated by LPA1.
      These data suggest that LPA exerts dual proliferative and proapoptotic actions
      mediated by specific LPA receptor subtypes.

PMID- 16890226
TI  - Mutations which decouple the proton pump of the cytochrome c oxidase from
      Rhodobacter sphaeroides perturb the environment of glutamate 286.
AB  - Mutants that decouple the proton pump of cytochrome c oxidase from Rhodobacter
      sphaeroides are postulated to do so by increasing the pK(a) of glutamate 286,
      which is 20 Angstrom away. The possibility that a conformational change near E286
      is induced by the decoupling mutations (N139D and N207D) was investigated by FTIR
      difference spectroscopy. In both decoupled mutants, the reduced-minus-oxidized
      FTIR difference spectra show a shift of 2 cm(-1) to lower frequency of the band
      resulting from the absorbance of E286 in the oxidized enzyme. The decoupling
      mutants may influence E286 by altering the chain of water molecules which runs
      from the site of the mutations to E286.

PMID- 16890227
TI  - Growth hormone and insulin-like growth factor-I act together and independently
      when regulating growth in vertebral and muscle tissue of atlantic salmon
      postsmolts.
AB  - Aiming to elucidate the role of GH and IGF-I with regard to vertebral and white
      muscle growth, gene expression of the GH and IGF-I receptors (ghr and igf-Ir,
      respectively) and local IGF-I (igf-I) were analyzed during spring growth (January
      June) in Atlantic salmon postsmolts. One group of fish was reared under natural
      light (NL), while one group was reared under continuous light (LL). Growth rate
      of fork length was higher in the LL group for a short period after onset of
      continuous light (LL: 0.50+/-0.02 mm day(-1), NL: 0.43+/-0.01 mm day(-1)) and for
      a longer period at the end of the experiment in June (LL: 1.18+/-0.06 mm day(-1),
      NL: 0.75+/-0.02 mm day(-1)). Likewise, growth rate in length of vertebra No. 40
      in the LL group was higher than in the NL group the first period after onset of
      light (LL: 0.015+/-0.002 mm day(-1), NL: 0.008+/-0.001 mm day(-1)). Plasma GH
      levels peaked in late February and were higher in the LL group than in the NL
      group (LL: 7.27+/-0.61 ng ml(-1), NL: 2.60+/-0.50 ng ml(-1)), whereas plasma IGF
      I levels peaked in early February and were unaffected by photoperiod. ghr
      expression was upregulated in late February in liver (12-fold), white muscle (6
      fold) and vertebral tissue (3-fold) and higher in the LL group than in the NL
      group (2-fold) in vertebral tissue in late March. White muscle expression of igf
      I and igf-Ir decreased from initial levels throughout the experiment. Hepatic
      gene expression of igf-I doubled in both groups in late February, followed by a 4
      fold upregulation in June in the LL group only. Vertebral tissue expression of
      igf-I (4-fold) and igf-Ir (6-fold) increased in May and were unaffected by
      photoperiod. One exception was a smaller upregulation of igf-I (2-fold) in the LL
      group in early February. In conclusion, GH appears to have an initial role in
      stimulating vertebral growth, while IGF-I seems to stimulate growth during late
      spring. It is suggested that local IGF-I acts as a paracrine agent, evaluated
      from the concurrent upregulation of igf-I and igf-Ir. The upregulation of ghr in
      white muscle tissue, concurrent with a downregulation of muscle igf-I and igf-Ir,
      indicate that GH stimulated growth or metabolism independent of IGF-I.

PMID- 16890228
TI  - Understanding eating disorders.
AB  - The outcome in eating disorders remains poor and commonly used methods of
      treatment have little, if any effect. It is suggested that this situation has
      emerged because of the failure to realize that the symptoms of eating disorder
      patients are epiphenomena to starvation and the associated disordered eating.
      Humans have evolved to cope with the challenge of starvation and the
      neuroendocrine mechanisms that have been under this evolutionary pressure are
      anatomically versatile and show synaptic plasticity to allow for flexibility.
      Many of the neuroendocrine changes in starvation are responses to the externally
      imposed shortage of food and the associated neuroendocrine secretions facilitate
      behavioral adaptation as needed rather than make an individual merely eat more or
      less food. A parsimonious, neurobiologically realistic explanation why eating
      disorders develop and why they are maintained is offered. It is suggested that
      the brain mechanisms of reward are activated when food intake is reduced and that
      disordered eating behavior is subsequently maintained by conditioning to the
      situations in which the disordered eating behavior developed via the neural
      system for attention. In a method based on this framework, patients are taught
      how to eat normally, their physical activity is controlled and they are provided
      with external heat. The method has been proven effective in a randomized
      controlled trial.

PMID- 16890229
TI  - Developmental and geographic variation in stress hormones in wild Belding's
      ground squirrels (Spermophilus beldingi).
AB  - Extensive research has been conducted on the role of glucocorticoids in
      regulating growth, mobilizing energy, responding to stressors and modulating
      learning and memory. However, little is known about the production of corticoids
      during early development in free-living animals, particularly during sensitive
      periods of acquisition of important behaviors. In a four-year study of Belding's
      ground squirrels, Spermophilus beldingi, a non-invasive assay of glucocorticoids
      was used to quantify age and population differences among juveniles from three
      California locations. Fecal-cortisol metabolites are elevated during a short
      period when juveniles first emerge aboveground from their natal burrows at about
      4 weeks of age. This period of cortisol elevation coincides with when young are
      learning survival behaviors such as anti-predator responses and foraging
      strategies. Population differences in juvenile cortisol levels, which may reflect
      local variation in habitat quality and predator environments, were not evident
      until 2 weeks after emergence. Elevated cortisol at the age of emergence was also
      observed in juveniles born and reared in captivity without exposure to typical
      stressors that occur around the age of emergence. These results indicate that
      corticoids are regulated during early development, and the possible functions of
      age-related corticoid levels are discussed, including mobilization of glucose for
      natal emergence and later facilitation of growth and energy storage during the
      short summer before hibernation. In some species, elevated corticoids can also
      facilitate learning and memory, and current work is exploring whether the higher
      cortisol observed in all three S. beldingi populations just after emergence
      function to promote rapid acquisition of survival behaviors.

PMID- 16890230
TI  - Neuropeptidergic regulation of affiliative behavior and social bonding in
      animals.
AB  - Social relationships are essential for maintaining human mental health, yet
      little is known about the brain mechanisms involved in the development and
      maintenance of social bonds. Animal models are powerful tools for investigating
      the neurobiological mechanisms regulating the cognitive processes leading to the
      development of social relationships and for potentially extending our
      understanding of the human condition. In this review, we discuss the roles of the
      neuropeptides oxytocin and vasopressin in the regulation of social bonding as
      well as related social behaviors which culminate in the formation of social
      relationships in animal models. The formation of social bonds is a hierarchical
      process involving social motivation and approach, the processing of social
      stimuli and formation of social memories, and the social attachment itself.
      Oxytocin and vasopressin have been implicated in each of these processes.
      Specifically, these peptides facilitate social affiliation and parental nurturing
      behavior, are essential for social recognition in rodents, and are involved in
      the formation of selective mother-infant bonds in sheep and pair bonds in
      monogamous voles. The convergence of evidence from these animal studies makes
      oxytocin and vasopressin attractive candidates for the neural modulation of human
      social relationships as well as potential therapeutic targets for the treatment
      of psychiatric disorders associated with disruptions in social behavior,
      including autism.

PMID- 16890232
TI  - General theory of indirect detection in chromatography.
AB  - Indirect detection is used in liquid chromatography to detect sample components
      that more or less lack detectable properties. A detectable component, the probe,
      is added to the mobile phase and the sample containing the components is
      injected. Every solute, even those not normally detectable, will give rise to
      detectable peaks due to the presence of the probe. The theory currently used to
      describe this situation is different for different adsorption isotherm models and
      also restrictions have to be imposed on the adsorption isotherm parameters. We
      present a general theory that describes both the retention times and areas of the
      detected peaks without making any a priori adsorption isotherm assumptions. Our
      general theory is compared with the current theory and validated by computer
      simulations. An alternative quantification method is suggested based on the
      measurement of the relative areas of the sample components without the
      requirement of having standard curves of known solutions of the sample
      components. Using this approach, the new theory is able to predict the solute
      concentrations in cases when the current theory did not, i.e., when the
      saturation capacities of the sample components and the probe differed from each
      other. In addition, a new application is proposed: the estimation of adsorption
      isotherm parameters.

PMID- 16890233
TI  - Effect of cationic surfactant adsorption on the rheological and surface
      properties of bentonite dispersions.
AB  - In this study, the adsorption, bridging, and intercalation effects of a cationic
      surfactant, benzyldimethyltetradecyl ammonium chloride (BDTDACl), on bentonite
      clay suspensions was investigated. The adsorption, rheological behaviors, and
      colloidal properties of the clay dispersions were determined as a function
      surfactant concentration. Adsorption isotherms were obtained using the batch
      equilibrium technique. The rheological behavior of the clay suspensions was
      obtained by shear stress-shear rate measurements within 0-350 s-1 shear rates.
      The structure of the composite particles was analyzed by using X-ray diffraction
      analysis and it was found that the expansions of basal d-spacings are less than
      16.80 A, suggesting a monolayer structure.

PMID- 16890231
TI  - Quantitative isolation and in vivo imaging of malaria parasite liver stages.
AB  - The liver stages of Plasmodium, the causative agent of malaria, are the least
      explored forms in the parasite's life cycle despite their recognition as key
      vaccine and drug targets. In vivo experimental access to liver stages of human
      malaria parasites is practically prohibited and therefore rodent model malaria
      parasites have been used for in vivo studies. However, even in rodent models
      progress in the analysis of liver stages has been limited, mainly due to their
      low abundance and associated difficulties in visualisation and isolation. Here,
      we present green fluorescent protein (GFP)-tagged Plasmodium yoelii rodent
      malaria parasite liver infections in BALB/c mice as an excellent quantitative
      model for the live visualisation and isolation of the so far elusive liver
      stages. We believe P. yoelii GFP-tagged liver stages allow, for the first time,
      the efficient quantitative isolation of intact early and late liver stage
      infected hepatocyte units by fluorescence activated cell sorting. GFP-tagged
      liver stages are also well suited for intravital imaging, allowing us for the
      first time to visualise them in real time. We identify previously unrecognised
      features of liver stages including vigorous parasite movement and expulsion of
      'extrusomes'. Intravital imaging thus reveals new, important information on the
      malaria parasite's transition from tissue to blood stage.

PMID- 16890234
TI  - Controlled production of ZnO nanoparticles from zinc glycerolate in a sol-gel
      silica matrix.
AB  - The controlled production of ZnO nanoparticles within an amorphous silica matrix
      is achieved using a new methodology consisting of four stages. First, precursor
      zinc glycerolate nanoparticles are produced within reversed micelles of glycerol
      in heptane stabilized by the surfactant Aerosol-OT (bis-ethylhexyl sodium
      sulfosuccinate, AOT). The surface of these nanoparticles is then modified by
      exchanging AOT with bis-trimethoxysilyl-ethane (BTME). The surface-modified
      nanoparticles are copolymerized with tetramethoxysilane (TMOS) to provide a
      composite silica material, in which the nanoparticles are apparently dissolved,
      producing a uniform distribution of zinc in the silica matrix. Finally, the
      conversion of zinc to ZnO is achieved by heating the material at 700 degrees C,
      leading to a uniform dispersion of very small (<10 nm) ZnO particles within the
      amorphous matrix. The fluorescence spectrum of the ZnO particles within the
      matrix is blue-shifted, as expected from the strong quantum confinement achieved.
      The properties of the system at all stages in this synthetic process are
      monitored using TEM, XRD, fluorescence and FT-IR spectroscopy. Glycerol forms
      complexes with many metal ions, so the present procedure may be generalized to
      provide uniform distributions of metal ions and subsequently metal oxide
      nanoparticles in amorphous silica.

PMID- 16890235
TI  - Numerical simulations of phase separation dynamics in a water-oil-surfactant
      system.
AB  - We have studied numerically the dynamics of the microphase separation of a water
      oil-surfactant system. We developed an efficient and accurate numerical method
      for solving the two-dimensional time-dependent Ginzburg-Landau model with two
      order parameters. The numerical method is based on a conservative, second-order
      accurate, and implicit finite-difference scheme. The nonlinear discrete equations
      were solved by using a nonlinear multigrid method. There is, at most, a first
      order time step constraint for stability. We demonstrated numerically the
      convergence of our scheme and presented simulations of phase separation to show
      the efficiency and accuracy of the new algorithm.

PMID- 16890236
TI  - Influences of acids and salts on the crystalline phase and morphology of TiO2
      prepared under ultrasound irradiation.
AB  - Nanocrystalline TiO2 powders were rapidly prepared by hydrolysis of Ti(OC4H9)4
      under ultrasound irradiation. The influences of acids (HCl, HNO3, and H2SO4) and
      their corresponding salts (NaCl, KNO3, and Na2SO4) on the crystalline phase and
      morphology of products were investigated, respectively. Compared with NaCl and
      KNO3 that show no evident influence on the crystalline phase, HCl and HNO3 have a
      decisive influence on the crystalline phase of the products. However, both H2SO4
      and Na2SO4 are favorable for the formation of anatase. By adjusting the
      concentration of SO2-(4) in the reaction medium, the contents of anatase and
      rutile phases in the TiO2 powders can be successfully controlled. The morphology
      of TiO2 crystallites are shown to be strongly related to the type of acid used in
      the reaction medium.

PMID- 16890237
TI  - Nanoparticle assembly on patterned "plus/minus" surfaces from electrospray of
      colloidal dispersion.
AB  - Selective deposition of metal (Au) and oxide (SiO2) nanoparticles with a size
      range of 10-30 nm on patterned silicon-silicon oxide substrate was performed
      using the electrospray method. Electrical charging characteristics of particles
      produced by the electrospray and patterned area created by contact charging of
      the electrical conductor with non- or semi-conductors were investigated.
      Colloidal droplets were electrosprayed and subsequently dried as individual
      nanoparticles which then were deposited on substrates, and observed using field
      emission-scanning electron microscopy. The number of elementary charge units on
      particles generated by the electrospray was 0.4-148, and patterned area created
      by contact charging contained sufficient negative charges to attract multiple
      charged particles. Locations where nanoparticles were (reversibly) deposited
      depended on voltage polarity applied to the spraying colloidal droplet and the
      substrate, and the existence of additional ions such as those from a stabilizer.

PMID- 16890238
TI  - Co-Pt alloy nanoparticles produced using a template of nanoparticle array.
AB  - A monolayer of Co-Pt alloy nanoparticles in the nanometer-size regime was
      fabricated using a nanotemplate approach. 1.7-nm-thick Co46Pt54 film was
      deposited onto a preexisting array of Ni seed particles embedded in a polyimide
      film. During subsequent annealing, the deposited Co46Pt54 film coalesced onto the
      seed particles to produce a monolayer of Co-Pt alloy particles. Deposition and
      annealing were repeated to increase both average particle size and volume
      fraction of the alloy particles. It was also shown that the annealing temperature
      was critical in controlling the particle size distribution and the final
      composition of the nanoparticles. This method of forming a single layer of
      vertically aligned nanoparticles can be easily extended to a large area as well
      as to produce a different combination of alloy particles on a polymer film.

PMID- 16890239
TI  - A stage-specific ovarian factor with stable stimulation of juvenile hormone
      synthesis in corpora allata of the cockroach Diploptera punctata.
AB  - This is a study of a feedback loop from a stimulated organ to glands that produce
      the stimulatory hormone in the cockroach Diploptera punctata. In this insect as
      in many others, juvenile hormone (JH) produced by corpora allata (CA) stimulates
      vitellogenesis. In our previous studies, transplantations of ovaries at certain
      stages of development into ovariectomized mated females stimulated JH synthesis
      within 24h. An in vitro study by other investigators showed that all stages of
      ovaries release a stimulatory factor into culture medium that was not retained on
      a solid-phase extraction column but occurred in the aqueous flow-through. The
      present study is a comparison of the effect of medium conditioned with ovaries
      from days 1-4 and 8 of the first reproductive cycle, to the effect of the flow
      through of that medium on members of a pair of CA from day 3 females. Results
      provide evidence for an ovarian factor that stimulates JH synthesis by CA in
      vitro after removal from the conditioning medium (i.e., stable stimulation). Only
      medium conditioned with ovaries from days 2 or 3 females significantly stimulated
      CA more than flow-through. Stimulation was dose dependent, sensitive to trypsin,
      and survived freezing. These results indicate that CA can be directly and stably
      stimulated by a stage-specific peptidergic ovarian factor.

PMID- 16890241
TI  - Crystal structure and nucleotide binding of the Thermus thermophilus RNA helicase
      Hera N-terminal domain.
AB  - DEAD box RNA helicases use the energy of ATP hydrolysis to unwind double-stranded
      RNA regions or to disrupt RNA/protein complexes. A minimal RNA helicase comprises
      nine conserved motifs distributed over two RecA-like domains. The N-terminal
      domain contains all motifs involved in nucleotide binding, namely the Q-motif,
      the DEAD box, and the P-loop, as well as the SAT motif, which has been implicated
      in the coordination of ATP hydrolysis and RNA unwinding. We present here the
      crystal structure of the N-terminal domain of the Thermus thermophilus RNA
      helicase Hera in complex with adenosine monophosphate (AMP). Upon binding of AMP
      the P-loop adopts a partially collapsed or half-open conformation that is still
      connected to the DEAD box motif, and the DEAD box in turn is linked to the SAT
      motif via hydrogen bonds. This network of interactions communicates changes in
      the P-loop conformation to distant parts of the helicase. The affinity of AMP is
      comparable to that of ADP and ATP, substantiating that the binding energy from
      additional phosphate moieties is directly converted into conformational changes
      of the entire helicase. Importantly, the N-terminal Hera domain forms a dimer in
      the crystal similar to that seen in another thermophilic prokaryote. It is
      possible that this mode of dimerization represents the prototypic architecture in
      RNA helicases of thermophilic origin.

PMID- 16890242
TI  - Exploring the short term visual store in schizophrenia using the attentional
      blink.
AB  - Schizophrenia patients exhibit numerous deficits on visual processing tasks,
      ranging from very early stages of visual processing (e.g., backward masking) to
      the later working memory stages (e.g., delayed match-to-sample, N-back). However,
      little is known about deficits in an intermediate stage of visual information
      processing, namely short term visual memory (STVM). The attentional blink (AB)
      paradigm is considered to be a valid way to assess the STVM, and recent studies
      have reported AB deficits in schizophrenia. However, it is not clear whether the
      reported AB deficit in schizophrenia patients is due to their increased
      susceptibility to backward masking or increased vulnerability in the STVM. In
      this study we first found poorer performance in the AB task in 37 schizophrenia
      patients compared to 26 normal controls. To examine the effects of increasing and
      decreasing mask strength on AB performance in patients and controls, we next
      systematically varied the masking effect by varying the length of the distracters
      immediately following the targets. The manipulation had relatively little effect
      on the patient--control differences and patients continued to show an enhanced AB
      effect across conditions. The findings suggest that the enhanced AB effect in
      schizophrenia reflects an abnormality in their short term visual memory, as
      opposed to their enhanced susceptibility to visual masking.

PMID- 16890240
TI  - Crystal structure of an active form of human MMP-1.
AB  - The extracellular matrix is a dynamic environment that constantly undergoes
      remodelling and degradation during vital physiological processes such as
      angiogenesis, wound healing, and development. Unbalanced extracellular matrix
      breakdown is associated with many diseases such as arthritis, cancer and
      fibrosis. Interstitial collagen is degraded by matrix metalloproteinases with
      collagenolytic activity by MMP-1, MMP-8 and MMP-13, collectively known as the
      collagenases. Matrix metalloproteinase 1 (MMP-1) plays a pivotal role in
      degradation of interstitial collagen types I, II, and III. Here, we report the
      crystal structure of the active form of human MMP-1 at 2.67 A resolution. This is
      the first MMP-1 structure that is free of inhibitor and a water molecule
      essential for peptide hydrolysis is observed coordinated with the active site
      zinc. Comparing this structure with the human proMMP-1 shows significant
      structural differences, mainly in the relative orientation of the hemopexin
      domain, between the pro form and active form of the human enzyme.

PMID- 16890243
TI  - The effect of pressure on the growth of tumour cell colonies.
AB  - This paper describes some experiments on the manner in which external pressure
      affects cell colony growth in general, and tumour growth in particular. More
      precisely, our results show that cell colony borders growing under high-pressure
      conditions have geometrical and dynamical properties that are markedly different
      from those corresponding to growth under homeostatic, normal pressure conditions.
      These behaviours are characterized by means of the so-called dynamical exponents
      of each type of growth. These are shown to correspond to statistical properties
      of solutions of some stochastic partial differential equations that account for
      the evolution of the interface between the expanding colony and the surrounding
      medium.

PMID- 16890245
TI  - Effects of tight blood pressure control on glomerular hypertrophy in a model of
      genetic hypertension and experimental diabetes mellitus.
AB  - The aim of this study was to evaluate the effect of prevention of hypertension on
      glomerular hypertrophy, renal cell replication and accumulation of glomerular
      fibronectin in a model of genetic hypertension and experimental diabetes. Four
      week-old streptozotocin induced spontaneously hypertensive rats (SHR) were
      randomized for no treatment, or for treatment with captopril, losartan or triple
      therapy (hydrochlorothiazide, reserpine and hydralazine) for 20 days. Increase in
      systolic blood pressure was equally prevented by captopril (118+/-15 mmHg),
      losartan (111+/-9) and triple therapy (112+/-14, p<0.0001). Glomerular size was
      higher (p<0.005) in diabetic SHR (27,300+/-2130 microm(2)) compared with non
      diabetic SHR (23,800+/-307). The antihypertensive therapy with captopril
      (23,900+/-175), losartan (23,800+/-120), and triple therapy (23,400+/-210)
      prevented the glomerular enlargement in diabetic SHR. Glomerular expression of
      fibronectin was increased in diabetic SHR (7.61+/-1.22 densitometric unit) as
      compared to the controls (2.27+/-2.15, p<0.0001), and was decreased (p<0.0001 vs
      diabetic SHR) with captopril (2.49+/-1.42), losartan (1.57+/-1.1) and triple
      therapy (2.04+/-1.42). The number of replicating glomerular cell significantly
      decreased in diabetic SHR and it was restored by all three antihypertensive
      regimes. The glomerular expression of p27(Kip1) was increased in diabetic SHR but
      it was not modified by antihypertensive treatment. Strict blood pressure control,
      in diabetic SHR independently of the class of antihypertensive agent, restores
      glomerular hypertrophy and renal cellular replication, and prevents the increment
      in glomerular fibronectin.

PMID- 16890244
TI  - Nitric oxide modulation of norepinephrine production in acupuncture points.
AB  - The purpose of this study was to examine the levels of norepinephrine (NE)
      turnover in skin tissues and to determine the effect of nitric oxide (NO) on NE
      production in acupuncture points (acupoints) and meridians. The rats were
      pretreated with alpha-methyl-tyrosine methyl ester and intravenously infused with
      L-(2,3,5,6-(3)H)-tyrosine. Blood was withdrawn and skin tissues were excised from
      the low skin resistance points, non-acupoint, and non-meridian areas located on
      leg, arm, or trunk. The results showed that the skin NE concentration and (3)H-NE
      release in acupoints were significantly higher than those in non-acupoints and
      non-meridian controls. (3)H-NE releases in the acupoints were increased by
      intravenous infusion of 2-N,N-diethylamino-diazenolate-2-oxide, an NO donor, but
      lowered by N(G)-Propyl-L-arginine, an inhibitor of neuronal NO synthesis. NE
      turnover rates in the acupoints were lower in the NO donor treated group while
      the inhibitor of NO synthesis reversed the trend. In contrast, NE turnover rates
      were not altered by NO donor and inhibitor of NO synthesis in non-acupoint and
      non-meridian control tissues. This is the first evidence that NE turnover was
      consistently decreased in acupoints and enhanced NE synthesis/release in
      acupoints were facilitated by presence of an NO donor and inhibited by an
      inhibitor of NO synthesis. The data suggest that skin NE synthesis/release in
      acupoints/meridians is increased in skin acupoints, which is modulated by L
      arginine-derived NO synthesis in sympathetic nervous system.

PMID- 16890246
TI  - Early renal structure alteration in rat offspring from dams fed low protein diet.
AB  - To investigate the early renal alterations due to severe maternal protein
      restriction (MPR) Wistar dams received 23% (normal protein, NP) or 5% (low
      protein, LP) chow during gestation and lactation periods. In NP offspring at
      birth, the cortex-to-medulla (C/M) ratio was 35% greater in female than in male
      offspring and the mature/immature glomeruli ratio was lower in both sexes of LP
      offspring than in the matched NP ones (by 20%). At birth and at weaning the
      kidney of the LP offspring showed fewer glomeruli (40% less) than the age-matched
      NP offspring. The NP female offspring had almost 20% fewer glomeruli than the
      matched male offspring. At weaning, the number of glomeruli was positively
      correlated with BM at birth (R=0.86; P<0.001). The effects of gender and maternal
      protein restriction, both individually and overall, based on biometrical and
      stereological parameters were: day 1, MPR largely responsible for the majority of
      alterations observed in LP groups, however gender influenced C/M ratio; day 21,
      MPR and gender interacted and modified the number of glomeruli per kidney. The
      early adverse of MPR effect on renal development is disproportionate between
      mature and immature glomeruli at birth leading to fewer glomeruli at weaning.
      This supports epidemiological data in humans underlying why fetuses with low
      birth weight carry an increased risk of mortality from chronic diseases in
      adulthood, including hypertension.

PMID- 16890247
TI  - Bioremediation and toxicity determination of natural seawater polluted with
      weathered crude oil by salt-tolerant consortia in a SBR.
AB  - The aim of this research was to compare the bioremediation treatment of seawater
      polluted with two different concentrations of weathered crude oil (0.2 for
      experiment (a) and 1.14% for experiment (b), v/v) by salt-tolerant consortia
      enriched from the sludge of a refinery wastewater treatment facility, in a SBR.
      The use of a commercial bioremediation stimulant (S200) was also evaluated as an
      alternative to the traditional nitrogen and phosphorus supplement.

PMID- 16890248
TI  - Nucleotide excision repair phenotype of human acute myeloid leukemia cell lines
      at various stages of differentiation.
AB  - In previous studies it was shown that nucleotide excision repair (NER) is
      strongly attenuated at the global genome level in terminally differentiated
      neuron-like cells. NER was measured in several human acute myeloid leukemia cell
      lines, before and after differentiation into macrophage-like cells. Repair of
      cisplatin intrastrand GTG crosslinks in differentiated cells was strongly
      attenuated. There were also some variations between repair levels in naive cells,
      but these were not correlated with the degree of differentiation. By contrast,
      the proficient repair of UV-induced (6-4)pyrimidine-pyrimidone photoproducts [(6
      4)PPs] was not affected by differentiation. Although cyclobutane pyrimidine
      dimers (CPDs) were poorly repaired at the global genome level in all cell lines,
      differentiated or not, they were very efficiently removed from the transcribed
      strand of an active gene, indicating that transcription-coupled repair (TCR) is
      proficient in each cell line. CPDs were also removed from the non-transcribed
      strand of an active gene better than at the overall global genome level. This
      relatively efficient repair of the non-transcribed strand of active genes, when
      compared with global genomic repair (GGR), has been described previously in
      neuron-like cells and termed differentiation-associated repair (DAR). Here we
      show that it also can occur in actively growing cells that display poor GGR.

PMID- 16890249
TI  - Synaptic strength at the thalamocortical input to layer IV neonatal barrel cortex
      is regulated by protein kinase C.
AB  - Long-term synaptic plasticity is an important mechanism underlying the
      development of cortical circuits in a number of brain regions. In barrel cortex
      NMDA receptor (NMDAR)-dependent long-term potentiation (LTP) and long-term
      depression (LTD) play a critical role in the development and experience-dependent
      plasticity of the topographical map of the rodent whiskers. However, the
      mechanisms underlying the induction and expression of these forms of plasticity
      are poorly characterised. Here we investigate the role of PKC in the regulation
      of synaptic strength in neonatal barrel cortex using patch-clamp recordings in
      brain slices. We demonstrate that PKC activity tonically maintains AMPA receptor
      mediated transmission at thalamocortical synapses, and that basal transmission
      can be potentiated by PKC activation using postsynaptic infusion of phorbol
      ester. Furthermore, we show that induction of NMDAR-dependent LTP requires PKC
      activity. These findings demonstrate that PKC is required for the regulation of
      transmission at thalamocortical synapses, the major ascending sensory input to
      barrel cortex. Thalamocortical inputs in barrel cortex only express LTP during
      the first postnatal week during a critical period for experience-dependent
      plasticity in layer IV. Therefore, the requirement for PKC in LTP suggests an
      important role for this kinase in the development of the barrel cortex sensory
      map.

PMID- 16890250
TI  - Dendritic calcium spikes induce bi-directional synaptic plasticity in the lateral
      amygdala.
AB  - Postsynaptic induction of long-term potentiation (LTP) at cortical and thalamic
      afferent synapses onto lateral amygdala (LA) projection neurons not only involves
      NMDA receptor activation, but also depends on L-type voltage-dependent calcium
      channels (L-VDCCs). Here we show, using whole cell recordings and two-photon Ca2+
      imaging, that L-VDCCs contribute to the induction of dendritic Ca2+ spikes in LA
      projection neurons. Dendritic Ca2+ spikes can be induced in the absence of sodium
      spikes by supra-threshold somatic depolarization or by pairing sub-threshold
      depolarization with synaptic stimulation. Moreover, synaptic induction of Ca2+
      spikes is facilitated by R-VDCCs in a pathway-specific manner. Once induced,
      dendritic Ca2+ spikes propagate into large parts of the dendritic tree. We show
      that pairing synaptic stimulation with single dendritic Ca2+ spikes can induce bi
      directional plasticity, the sign of which might be determined by the anatomical
      location of active synaptic inputs relative to the spike initiation zone. These
      data suggest an important role for dendritic Ca2+ spikes in dendritic integration
      and provide a mechanism by which local synaptic activity may influence global
      dendritic integration in LA projection neurons.

PMID- 16890251
TI  - Preclinical evaluation of 2,2,3,3-tetramethylcyclopropanecarbonyl-urea, a novel,
      second generation to valproic acid, antiepileptic drug.
AB  - 2,2,3,3-Tetramethylcyclopropanecarbonylurea (TMCU) is an amide derivative of a
      tetramethylcyclopropyl analogue of valproic acid (VPA), one of the leading
      antiepileptic drugs. Structural considerations used in the design of TMCU aimed
      to enhance the anticonvulsant potency of VPA and to prevent its two life
      threatening side effects; i.e., teratogenicity and hepatotoxicity. The
      anticonvulsant activity of TMCU was evaluated in the MES, scMet, 6-Hz, scBic and
      scPic tests, and also in the hippocampal kindling model of partial seizures and
      lamotrigine-resistant amygdala kindling model of therapy-resistant seizures.
      Minimal motor impairment was determined using the rotorod test in mice and the
      positional sense test, muscle tone test, and gait and stance test in rats. The
      antinociceptive effect of TMCU was evaluated in the mouse formalin model of acute
      tonic pain. The molecular mechanisms of action of TMCU were investigated in
      electrophysiological studies using the whole-cell patch-clamp technique.
      Teratogenicity studies were performed in a SWV/Fnn-mouse model of VPA-induced
      teratogenicity. TMCU hepatotoxicity was evaluated following 1-week
      intraperitoneal and oral administration of 50, 250 and 500 mg/kg doses to rats.
      In the hepatotoxicity study the blood levels of TMCU were evaluated at day 1 and
      day 7 of the treatment. TMCU mutagenicity was evaluated in the Ames test.

PMID- 16890252
TI  - GABAA receptor-associated phosphoinositide 3-kinase is required for insulin
      induced recruitment of postsynaptic GABAA receptors.
AB  - Type A gamma-aminobutyric acid (GABAA) receptors mediate most of the fast
      inhibitory synaptic transmission within the vertebrate brain. The regulation of
      this inhibition is vital in modulating neural activity. One regulator of GABAA
      receptor function is insulin, which can serve to enhance GABAA receptor-mediated
      miniature inhibitory postsynaptic currents, via an increase in the number of
      receptors at the plasma membrane. We set out to investigate the molecular
      mechanisms involved in the insulin-induced potentiation of GABAA receptor
      mediated responses, by examining the role of phosphoinositide 3-kinase (PI3-K), a
      key mediator of the insulin response within the brain. We found that PI3-K
      associates with the GABAA receptor, and this interaction is increased following
      insulin treatment. Additionally, the beta2 subunit of the GABAA receptor appears
      to mediate the insulin-stimulated association with the N-terminal SH2 domain of
      the p85 subunit of PI3-K. Our results imply a mechanism whereby insulin can
      regulate changes in synaptic transmission through its downstream actions on the
      GABAA receptor.

PMID- 16890253
TI  - Central versus lateral presentation in hemispheric sentence processing: a
      paradoxical finding.
AB  - There is considerable current interest in the question of the contribution of the
      right cerebral hemisphere to the comprehension of complex linguistic entities
      such as sentences and scripts. A problem in this field has been the difficulty of
      distinguishing between the consequences of lexical and message-level activation.
      The present study used a cross-modal lexical priming (CMLP) procedure to visually
      sample activation of word concepts at three different points during the auditory
      presentation of a sentence. Our aim was to contrast direct lexical activation
      following presentation of a word in the sentence with syntactic reactivation
      triggered by a subsequent anaphor. Visual word probes were presented to the
      right, left, and central visual fields, in order to permit hemispheric
      performance to be evaluated in relation to previous research confined to central
      presentations. The results were surprising. LVF probes revealed activation
      immediately following the target word, RVF probes exhibited activation three
      words downstream from the target, and centrally presented probes exhibited
      activation at all three sampling points. The most puzzling aspect of these
      results was the paradoxical finding that central presentations showed strong
      activation upon encountering an anaphor of the target, while neither lateral
      probe revealed any activation at all. We relate these results to recent research
      on the hemispheric implications of split-foveal word presentation, and suggest
      that simultaneous stimulation of the two hemispheres may be critical in evoking
      responses mediated by high-level integrative mechanisms requiring collaborative
      hemispheric processing.

PMID- 16890255
TI  - Glucuronide triterpene saponins from Bersama engleriana.
AB  - Five 3-O-glucuronide triterpene saponins (1-5) were isolated from the stem bark
      of Bersama engleriana Gurke along with two known saponins, polyscias saponin C
      and aralia saponin 15, and one major C-glycoside xanthone, mangiferin. The
      structures of the saponins were established mainly by means of spectroscopic
      methods (one- and two-dimensional NMR spectroscopy as well as FAB-, HRESI-mass
      spectrometry) as 3-O-[beta-D-glucopyranosyl-(1-->2)-beta-D-glucuronopyranosyl]-28
      O-[beta-D-glucopyranosyl]-betulinic acid (1), 3-O-[beta-D-glucopyranosyl-(1-->2)
      [beta-D-galactopyranosyl-(1-->3)]-beta-D-glucuronopyranosyl]-oleanolic acid (2),
      3-O-[beta-D-glucopyranosyl-(1-->3)-beta-D-glucuronopyranosyl]-28-O-[beta-D
      xylopyranosyl-(1-->6)-beta-d-glucopyranosyl]-oleanolic acid (3), 3-O-[beta-D
      galactopyranosyl-(1-->3)-beta-D-glucuronopyranosyl]-28-O-[beta-D-glucopyranosyl
      (1-->4)-beta-D-glucopyranosyl]-oleanolic acid (4), and 3-O-[beta-d-glucopyranosyl
      (1-->3)-beta-D-galactopyranosyl-(1-->3)-beta-D-glucuronopyranosyl]-28-O-[beta-d
      xylopyranosyl-(1-->6)-beta-D-glucopyranosyl]-oleanolic acid (5).

PMID- 16890254
TI  - Stilbenoids from Tragopogon orientalis.
AB  - A phytochemical investigation of Tragopogon orientalis L. (Asteraceae,
      Cichorieae) yielded the natural products 6''-O-(7,8-dihydrocaffeoyl)-alpha,beta
      dihydrorhaponticin, 3'-O-methyl-alpha,beta-dihydrorhaponticin, and (S)-3-(4-beta
      glucopyranosyloxybenzyl)-7-hydroxy-5-methoxyphtalide as well as known compounds
      alpha,beta-dihydrorhaponticin, 3-(4-methoxybenzyl)-5,7-dimethoxyphthalide, p
      dihydrocoumaric acid methyl ester, and 1-hydroxypinoresinol-1-O-beta
      glucopyranoside. The structures were established by HR mass spectrometry,
      extensive 1D and 2D NMR spectroscopy, and CD spectroscopy. Moreover, the radical
      scavenging activities of the major compounds were measured using the 2,2-diphenyl
      1-picrylhydrazyl (DPPH) assay. The chemosystematic impact of the occurrence of
      stilbene derivatives in T. orientalis is discussed.

PMID- 16890256
TI  - Changes in Wuchereria bancrofti infection in a highly endemic community following
      10 rounds of mass administration of diethylcarbamazine.
AB  - Mass drug administration (MDA) is the principal strategy of the programme to
      eliminate lymphatic filariasis (LF). Evaluation of MDA in highly endemic
      'sentinel' communities is necessary to understand its impact on LF infection.
      This study examined the changes in Wuchereria bancrofti infection following 10
      rounds of annual mass administration of diethylcarbamazine (DEC) in a highly
      endemic community. The mean number of DEC treatments received per adult in the
      community was 7.4+/-2.0. Following 10 rounds of DEC administration, the number of
      microfilaria (mf) carriers fell from 565 to 55. None of the pre-MDA
      amicrofilaraemic individuals showed circulating filarial antigen (CFA). However,
      54.5% of the pre-MDA microfilaraemic individuals were positive for CFA. All the
      pre-MDA high intensity mf carriers continued to be positive for CFA, and some of
      them also showed blood mf. These patients are the most difficult to be cured by
      MDA and were distributed in 8.2% of the households. All the children born during
      the last 7 years of the MDA programme were negative for CFA. The study suggests
      that six to seven DEC treatments per individual suppresses microfilaraemia,
      except in some people with heavy infection, and repeated MDA has very good
      potential to prevent infection in children.

PMID- 16890257
TI  - Human fascioliasis infection: gender differences within school-age children from
      endemic areas of the Nile Delta, Egypt.
AB  - Several studies have reported a higher prevalence of infection for human
      fascioliasis among girls than among boys. To investigate this aspect further a
      sufficiently large data set was assembled comprising of 21,477 subjects with 932
      positive cases. Subjects were primary school children covered by a control
      programme implemented by the Egyptian Ministry of Health and Population in the
      Nile Delta from 1988 to 2002. Stool analyses were performed by the Kato-Katz
      thick smear technique for a quantitative diagnosis on the intensity of infection.
      Both prevalence and intensity of infection, indirectly measured as mean number of
      eggs per gram of faeces, were significantly higher among girls than boys. The
      higher level of infection in girls was consistent across different years and in
      different survey areas. Co-infection with Schistosoma mansoni was present and
      associated with fascioliasis, but schistosomiasis was significantly more
      prevalent among boys. In Egypt rural girls are often involved in household and
      farm work and are exposed more than boys to infected foci. The lower school
      attendance for girls in rural areas appears to be an important factor increasing
      risk of infection. The precise mode of transmission and behavioural risk factors
      for human infection need to be investigated further to identify those related to
      gender.

PMID- 16890258
TI  - A regioselective cyanohydration of steroidal 17-ketones and the configuration of
      the resulted cyanohydrins.
AB  - Cyanohydration of some 17-keto steroids with 4-en-3-one or 1,4-dien-3-one unit
      showed high regioselectivity to give 17-cyanohydrins with high yields when the
      reaction was carried out under acetone cyanohydrin/K2CO3 in aq. MeOH. The crystal
      X-ray exhibited the configuration of resulted cyanohydrins were depended on the
      structure of substrates.

PMID- 16890259
TI  - Interplay of Darwinian and frequency-dependent selection in the host-associated
      microbial populations.
AB  - In order to analyze the microevolutionary processes in host-associated
      microorganisms, we simulated the dynamics of rhizobia populations composed of a
      parental strain and its mutants possessing the altered fitness within "plant
      soil" system. The population dynamics was presented as a series of cycles (each
      one involves "soil-->rhizosphere-->nodules-->soil" succession) described using
      recurrent equations. For representing the selection and mutation pressures, we
      used a universal approach based on calculating the shifts in the genetic ratios
      of competing bacterial genotypes within the particular habitats and across
      several habitats. Analysis of the model demonstrated that a balanced polymorphism
      may be established in rhizobia population: mutants with an improved fitness do
      not supplant completely the parental strain while mutants with a decreased
      fitness may be maintained stably. This polymorphism is caused by a rescue of low
      fitted genotypes via negative frequency-dependent selection (FDS) that is
      implemented during inoculation of nodules and balances the Darwinian selection
      that occurs during multiplication or extinction of bacteria at different
      habitats. The most diverse populations are formed if the rhizobia are equally
      successful in soil and nodules, while a marked preference for any of these
      habitats results in the decrease of diversity. Our simulation suggests that FDS
      can maintain the mutualistic rhizobia-legume interactions under the stress
      conditions deleterious for surviving the bacterial strains capable for intensive
      N2 fixation. Genetic consequences of releasing the modified rhizobia strains may
      be addressed using the presented model.

PMID- 16890260
TI  - Mosla dianthera inhibits mast cell-mediated allergic reactions through the
      inhibition of histamine release and inflammatory cytokine production.
AB  - In this study, we investigated the effect of the aqueous extract of Mosla
      dianthera (Maxim.) (AEMD) on the mast cell-mediated allergy model and studied the
      possible mechanism of action. Mast cell-mediated allergic disease is involved in
      many diseases such as asthma, sinusitis and rheumatoid arthritis. The discovery
      of drugs for the treatment of allergic disease is an important subject in human
      health. AEMD inhibited compound 48/80-induced systemic reactions in mice. AEMD
      decreased immunoglobulin E-mediated local allergic reactions, passive cutaneous
      anaphylaxis. AEMD attenuated intracellular calcium level and release of histamine
      from rat peritoneal mast cells activated by compound 48/80. Furthermore, AEMD
      attenuated the phorbol 12-myristate 13-acetate (PMA) and calcium ionophore A23187
      stimulated TNF-alpha, IL-8 and IL-6 secretion in human mast cells. The inhibitory
      effect of AEMD on the pro-inflammatory cytokines was nuclear factor-kappaB (NF
      kappaB) dependent. AEMD decreased PMA and A23187-induced degradation of
      IkappaBalpha and nuclear translocation of NF-kappaB. Our findings provide
      evidence that AEMD inhibits mast cell-derived immediate-type allergic reactions
      and involvement of pro-inflammatory cytokines and NF-kappaB in these effects.

PMID- 16890261
TI  - Methoxychlor causes mitochondrial dysfunction and oxidative damage in the mouse
      ovary.
AB  - Methoxychlor (MXC) is an organochlorine pesticide that reduces fertility in
      female rodents by causing ovarian atrophy, persistent estrous cyclicity, and
      antral follicle atresia (apoptotic cell death). Oxidative damage resulting from
      reactive oxygen species (ROS) generation has been demonstrated to lead to
      toxicant-induced cell death. Thus, this work tested the hypothesis that MXC
      causes oxidative damage to the mouse ovary and affects mitochondrial respiration
      in a manner that stimulates ROS production. For the in vitro experiments,
      mitochondria were collected from adult cycling mouse ovaries, treated with
      vehicle (dimethyl sulfoxide; DMSO) or MXC, and subjected to polarographic
      measurements of respiration. For the in vivo experiments, adult cycling CD-1 mice
      were dosed with either vehicle (sesame oil) or MXC for 20 days. After treatment,
      ovarian mitochondria were isolated and subjected to measurements of respiration
      and fluorimetric measurements of H2O2 production. Some ovaries were also fixed
      and processed for immunohistochemistry using antibodies for ROS production
      markers: nitrotyrosine and 8-hydroxy-2'-deoxyguanosine (8-OHG). Ovaries from in
      vivo experiments were also used to measure the mRNA expression and activity of
      antioxidants such as Cu/Zn superoxide dismutase (SOD1), glutathione peroxidase
      (GPX), and catalase (CAT). The results indicate that MXC significantly impairs
      mitochondrial respiration, increases production of H2O2, causes more staining for
      nitrotyrosine and 8-OHG in antral follicles, and decreases the expression and
      activity of SOD1, GPX, and CAT as compared to controls. Collectively, these data
      indicate that MXC inhibits mitochondrial respiration, causes ROS production, and
      decreases antioxidant expression and activity in the ovary, specifically in the
      antral follicles. Therefore, it is possible that MXC causes atresia of ovarian
      antral follicles by inducing oxidative stress through mitochondrial production of
      ROS.

PMID- 16890262
TI  - The anti-snake venom activities of the methanolic extract of the bulb of Crinum
      jagus (Amaryllidaceae).
AB  - The anti-snake venom activities of the methanolic extract of the bulb of Crinum
      jagus plant (Amaryllidaceae) were investigated in vitro and in vivo against the
      venoms of three notable snake species: Echis ocellatus, Bitis arietans and Naja
      nigricollis. The extract was prepared by cold marceration in 50% methanol at 37
      degrees C with intermittent shaking for 48 h. An yield of 12.8% w/w dry extract
      was obtained. Oral administration of C. jagus extract (1000 mg/kg) protected 50%
      of mice, while injection of a 30 min pre-incubated mixture of the same dose of
      extract and venom gave 100% protection against the lethal effects of E. ocellatus
      venom (10 mg/kg, i.m.). The intraperitoneal administration of the extract at 250
      mg/kg, 30 min before the injection of E. ocellatus venom (10mg/kg, i.m.),
      significantly (p<0.05) prolonged the death time of poisoned mice. C. jagus
      extract (500 mg/kg, per os), gave 50% protection against B. arietans venom
      (9.5mg/kg, i.m.) in mice while the pre-incubation of a mixture of the same dose
      of venom and extract (500 mg/kg), prior to injection (i.p.) of the mixture, gave
      only 33.3% protection. The pre-incubation of 500 mg/kg of C. jagus extract with
      N. nigricollis venom (6 mg/kg) prior to i.p. injection of the mixture protected
      50% of the treated mice. There were generally no significant differences in the
      death times of mice that were given the same dose of the extract orally 30 min
      before injection of the venoms and those administered with the pre-incubated
      mixtures of venom and extract. The pre-incubation of the extract and E. ocellatus
      venom (5mg/kg) for 30 min, before the i.m. injection of the mixture,
      significantly reduced infiltration of inflammatory cells to the site of injection
      4h post treatment. The concentrations of plasma creatine kinase in poisoned mice
      were significantly (p<0.01 or p<0.05) reduced after the injection (i.p.) of C.
      jagus extract (1000 mg/kg) pre-incubated with E. ocellatus (5mg/kg) or B.
      arietans (7 mg/kg) venom, respectively. The bulb extract of C. jagus blocked the
      haemorrhagic activity of a standard haemorrhagic dose (2.8 mg/ml) of E. ocellatus
      venom at various concentrations (1.7, 3.3 and 6.7 mg/ml). The methanolic bulb
      extract of C. jagus was therefore able to significantly protect mice from death,
      myonecrosis and haemorrhage induced by the lethal effects of venoms of notable
      snake species in Nigeria.

PMID- 16890263
TI  - Production of monoclonal antibodies for sandwich immunoassay detection of
      ciguatoxin 51-hydroxyCTX3C.
AB  - Every year, more than 50,000 people in subtropical and tropical regions suffer
      from ciguatera seafood poisoning. The extremely low level of the causative
      neurotoxins (ciguatoxins) in fish has hampered the preparation of antibodies for
      detection of the toxins. In this study, we produced a monoclonal antibody (8H4)
      against the right end of ciguatoxin CTX1B (1) and 51-hydroxyCTX3C (3) by
      immunizing mice with the keyhole limpet hemocyanin-conjugate of the synthetic
      HIJKLM ring fragment (10). We used 8H4 and another previously reported monoclonal
      antibody (10C9) that recognizes the left end of 3 to develop a sandwich enzyme
      linked immunosorbent assay (ELISA) to detect 3. The assay could detect 3 down to
      the ppb level and lacked cross-reactivity with other related marine toxins,
      including brevetoxin A, brevetoxin B, okadaic acid, and maitotoxin.

PMID- 16890264
TI  - Sonodynamic effects of protoporphyrin IX disodium salt on isolated sarcoma 180
      cells.
AB  - The cytotoxic effect of PPIX on isolated sarcoma 180 cells induced by ultrasound
      was investigated. Tumor cells suspended in air-saturated PBS (pH 7.2) were
      exposed to ultrasound at 2.2 MHz for up to 60s in the presence and absence of
      protoporphyrin IX disodium salt (PPIX). The viability of cells was determined by
      a trypan blue exclusion test. The rate of ultrasonically induced cell damage was
      increased with 40-160 microM PPIX, while no cell damage was observed with 160
      microM PPIX alone. This enhancement of cell damage with PPIX was inhibited by
      histidine. The participation of lipid peroxidation products in the cell damage
      process was also investigated. Scanning electron microscope (SEM) observation of
      the surface of cells was performed to evaluate the morphological changes induced
      by ultrasonic irradiation. The results indicate the involvement of a sonochemical
      mechanism.

PMID- 16890265
TI  - Experimental and finite element modelling studies on single-layer and multi-layer
      1-3 piezocomposite transducers.
AB  - Finite element modelling (FEM) using ATILA code and experimental studies have
      been carried out on 1-3 piezocomposite transducers. FEM study was initially
      carried out on a piezocomposite infinite plate and then extended to transducers
      of finite size. The infinite-plate model results agree well with that of a simple
      analytical model and experiments. The acoustic performance of multi-layer finite
      size piezocomposite transducers was also studied. Transducer stacks were
      fabricated with different number of layers. The transducer characteristics such
      as the electrical impedance, the transmitting voltage response (TVR) and the
      receiving sensitivity (RS) of the 1-3 piezocomposite transducers were evaluated
      as functions of frequency, ceramic volume fractions and the number of layers. TVR
      increases and RS decreases with increase in ceramic volume fractions. The model
      results are found to agree with the experimental data, especially when the number
      of layers is less.

PMID- 16890267
TI  - Calcium-dependent viral internalization is required for adenovirus type 7
      induction of IL-8 protein.
AB  - The host response to adenovirus (Ad) infection involves induction of cytokines in
      lung epithelia. We have demonstrated induction of the lung neutrophil chemokine
      interleukin-8 (IL-8) by Ad7, a major lung pathogen, in A549 lung epithelial cells
      and lung tissue through activation of the Erk signaling pathway. However, the
      mechanism of IL-8 induction is still unclear. In this paper, we first showed that
      Ad7 viral gene expression is not essential for IL-8 induction as psoralen-UV
      inactivation of Ad7 did not affect IL-8 mRNA induction or IL-8 protein induction
      in A549 cells. We then inhibited internalization of Ad7 by treatment of A549
      cells with EGTA in calcium-free medium during exposure to Ad7. We verified that
      this treatment inhibited Ad internalization by confocal microscopy, FACS analysis
      and Ad E1A and fiber mRNA expression. Preventing internalization by calcium
      depletion did not inhibit Erk activation by Ad7. However, calcium-dependent
      internalization was required for IL-8 protein production in Ad7 exposed cells.
      This is not likely due to an effect of calcium depletion on downstream Erk
      signaling or IL-8 protein production since calcium depletion did not block IL-8
      protein production stimulated by PMA, and because addition of EGTA subsequent to
      Ad7 internalization also did not prevent Ad induction of IL-8. These studies
      indicate that Ad7 internalization is calcium-dependent and is required for IL-8
      protein induction upon Ad7 infection. Ad7 induction of Erk is independent of
      calcium and does not require virus internalization.

PMID- 16890268
TI  - Environmental impact of a coal combustion-desulphurisation plant: abatement
      capacity of desulphurisation process and environmental characterisation of
      combustion by-products.
AB  - The fate of trace elements in a combustion power plant equipped with a wet
      limestone flue gas desulphurisation (FGD) installation was studied in order to
      evaluate its emission abatement capacity. With this aim representative samples of
      feed coal, boiler slag, fly ash, limestone, FGD gypsum and FGD process water and
      wastewater were analysed for major and trace elements using the following
      techniques: inductively coupled plasma-mass spectrometry (ICP-MS), inductively
      coupled plasma-atomic emission spectrometry (ICP-AES), ion chromatography (IC),
      ion selective electrode (ISE) and atomic absorption spectroscopy (AAS). Mass
      balances were established allowing to determine the element partitioning
      behaviour. It was found that, together with S, Hg, Cl, F, Se and As were those
      elements entering in the FGD plant primarily as gaseous species. The abatement
      capacity of the FGD plant for such elements offered values ranged from 96% to
      100% for As, Cl, F, S and Se, and about 60% for Hg. The environmental
      characterisation of combustion by-products (boiler slag, fly ash and FGD gypsum)
      were also established according to the Council Decision 2003/33/EC on waste
      disposal. To this end, water leaching tests (EN-12457-4) were performed,
      analysing the elements with environmental concern by means of the aforementioned
      techniques. According to the leaching behaviour of combustion by-products
      studied, these could be disposed of in landfills for non-hazardous wastes.

PMID- 16890266
TI  - Histone acetyltransferase (HAT) activity of p300 modulates human T lymphotropic
      virus type 1 p30II-mediated repression of LTR transcriptional activity.
AB  - Human T-lymphotropic virus type-1 (HTLV-1) is a deltaretrovirus that causes adult
      T cell leukemia/lymphoma, and is implicated in a variety of lymphocyte-mediated
      inflammatory disorders. HTLV-1 provirus has regulatory and accessory genes in
      four pX open reading frames. HTLV-1 pX ORF-II encodes two proteins, p13II and
      p30II, which are incompletely defined in virus replication or pathogenesis. We
      have demonstrated that pX ORF-II mutations block virus replication in vivo and
      that ORF-II encoded p30II, a nuclear-localizing protein that binds with CREB
      binding protein (CBP)/p300, represses CREB and Tax responsive element (TRE)
      mediated transcription. Herein, we have identified p30II motifs important for
      p300 binding and in regulating TRE-mediated transcription in the absence and
      presence of HTLV-1 provirus. Within amino acids 100-179 of p30II, a region
      important for repression of LTR-mediated transcription, we identified a single
      lysine residue at amino acid 106 (K3) that significantly modulates the ability of
      p30II to repress TRE-mediated transcription. Exogenous p300, in a dose-responsive
      manner, reverses p30II-dependent repression of TRE-mediated transcription, in the
      absence or presence of the provirus, In contrast to wild type p300, p300 HAT
      mutants (defective in histone acetyltransferase activity) only partially rescued
      p30(II)-mediated LTR repression. Deacetylation by histone deacetylase-1 (HDAC-1)
      enhanced p30II-mediated LTR repression, while inhibition of deacetylation by
      trichostatin A decreases p30(II)-mediated LTR repression. Collectively, our data
      indicate that HTLV-1 p30II modulates viral gene expression in a cooperative
      manner with p300-mediated acetylation.

PMID- 16890269
TI  - Effect of tributyltin on veliger larvae of the Manila clam, Ruditapes
      philippinarum.
AB  - We investigated the effects of waterborne and maternal exposure to tributyltin
      (TBT) on veliger larvae of the Manila clam, Ruditapes philippinarum. In a
      waterborne exposure test, veliger larvae (D-larvae stage: 24h after
      fertilization) were exposed to TBT at measured concentrations of <0.01 (control),
      0.055, 0.130, 0.340, and 0.600microg/l for 13d. The percentage of normal veliger
      larvae (the ratio of normal veliger larvae to all larvae) decreased significantly
      in all TBT treatment groups compared with that in the control group. In a
      maternal exposure test, 100 clams were exposed to TBT at measured concentrations
      of <0.01 (control), 0.061, and 0.310microg/l at 20-22 degrees C for 3 weeks, and
      the percentage of normal veliger larvae assessed for 13d. No maternal effects on
      veliger larvae from TBT were observed in TBT treatment groups as compared with
      the control group. These results demonstrate that waterborne TBT affects Manila
      clam veliger larvae, and indicates that TBT may have reduced Manila clam
      populations by preventing the development and survival of veliger larvae.

PMID- 16890270
TI  - Experimental Zn(II) retention in a sandy loam soil by very small columns.
AB  - The use of column experiments, usually performed to better approximate field
      conditions, may provide information that is not available from batch experiments.
      In such experiments heavy metals are often adsorbed until saturation followed by
      desorption experiments. When the affinity of the metal to soil is high, the
      retention factor (R) could be greater than thousands and the duration of
      experiments can become impractically long. In order to use reasonable laboratory
      time, the flow rate should be increased or the column size decreased. The
      increase in flow rate produces undesirable kinetic and dispersion effects, so we
      used very small soil columns (pore volume=0.31-0.70 ml) and relatively high flow
      rates (0.03-0.12 ml min(-1)) in studies of Zn(II) adsorption and retention in
      soils. Conservative tracer flow column experiments under saturation conditions
      were carried out to determine flow parameters for different flow rates. Column
      pore volume (V(p)), Peclet numbers (Pe) and longitudinal dispersion coefficients
      (D(L)) were determined from breakthrough curves. The effect of type of
      electrolyte and ionic strength on the Zn(II) retention onto soil was determined.
      The influence of flow rate and bed height on the retention coefficient and on the
      mass transfer zone was also studied. The effect of different influent Zn(II)
      concentrations on the R values obtained was analyzed. Freundlich parameters from
      column experiments were compared with batch ones. The leaching efficiency of
      different electrolytes, salts of weak organic acids and EDTA was also studied.

PMID- 16890271
TI  - Can topological indices be used to predict gas-phase rate coefficients of
      importance to tropospheric chemistry? Reactions of alkenes with OH, NO3 and O3.
AB  - Rate coefficients for the gas-phase reactions of unsaturated hydrocarbons with
      OH, NO(3) and O(3) are of vital importance to atmospheric modelling. Many of
      these rate coefficients are unknown--possibly resulting from the variety of these
      compounds and the inherent expense of deriving these data experimentally--and a
      reliable method for their prediction would therefore be of value to such models.
      This study presents a method for estimating rate coefficients for C(2)-C(10)
      olefins. Measured rate coefficients for the reaction of unsaturated hydrocarbons
      with OH and NO(3) radicals and O(3) are correlated with the Randic topological
      descriptor and an established correlation parameter, i.e. ionization potentials
      calculated using the frontier molecular orbital (FMO) approach. Although the
      ionization potential method produces better correlations in general, OH
      correlations of aliphatic species, subdivided into groups of varying total number
      of primary (1 degree), secondary (2 degrees) and tertiary (3 degrees) carbon
      atoms (Sigma x degrees (x)) produced several new trends with the Randic index
      that were not present in the ionization potential correlations. Strong
      correlation was observed with a Randic-type index optimized to include a term for
      side chain length (Sigma x degrees (x)). The presence of strong relationships,
      made predictable by molecular constitution, makes topological descriptors a
      useful and accessible tool for estimating rate coefficients for the reactions of
      OH with aliphatic species. This study indicates that alkene reactivity is
      affected strongly by constitution and that abstraction as well as addition may be
      important for some classes of compound.

PMID- 16890272
TI  - Evolution of brain size and juvenile periods in primates.
AB  - This paper assesses selective pressures that shaped primate life histories, with
      particular attention to the evolution of longer juvenile periods and increased
      brain sizes. We evaluate the effects of social complexity (as indexed by group
      size) and foraging complexity (as indexed by percent fruit and seeds in the diet)
      on the length of the juvenile period, brain size, and brain ratios (neocortex and
      executive brain ratios) while controlling for positive covariance among body
      size, life span, and home range. Results support strong components of diet, life
      span, and population density acting on juvenile periods and of home range acting
      on relative brain sizes. Social-complexity arguments for the evolution of primate
      intelligence are compelling given strong positive correlations between brain
      ratios and group size while controlling for potential confounding variables. We
      conclude that both social and ecological components acting at variable
      intensities in different primate clades are important for understanding variation
      in primate life histories.

PMID- 16890273
TI  - Effects of fish farming on flavonoids in Posidonia oceanica.
AB  - This work is a first approach to flavonoid responses (total proanthocyanidins and
      total and simple flavonols) in Posidonia oceanica in function of nutrient
      enrichment (aquaculture activities - fish farming), in the western Mediterranean
      Sea (Calvi-Corsica-France). The first result is the presence of total and simple
      flavonoids in P. oceanica. The second result shows an increase in total
      proanthocyanidin and total flavonol concentrations near cages, which would be
      linked to the high grazing pressure induced by meadow enrichment. Concerning
      simple flavonols, only quercetin shows a response to fish farming, which could be
      due to its strong antioxidant capacity. The presence of fish farming, which
      causes variations in environmental parameters, could affect the functioning of P.
      oceanica meadows. Flavonoid concentrations in P. oceanica seem to be a possible
      bioindicator of nutrient enrichment for the management of the littoral
      environment.

PMID- 16890274
TI  - Clusterin confers paclitaxel resistance in cervical cancer.
AB  - OBJECTIVE: To measure clusterin expression in cervical cancer tissues and cell
      lines and to evaluate whether clusterin confers resistance to paclitaxel in
      cervical cancer cells. METHODS: Immunohistochemical staining for clusterin was
      performed on 15 normal cervical tissues and 32 primary cervical cancer tissues,
      and clusterin expression in cervical cancer cell lines was quantified by Western
      blotting. The correlation between clusterin expression level and paclitaxel IC50
      in cervical cancer cell lines was evaluated. The effect of clusterin siRNA on
      paclitaxel resistance was evaluated by XTT assays. RESULTS: Cervical cancer
      tissues expressed significantly higher levels of clusterin than did normal
      cervical tissues (4.08 vs. 1.35, P<0.05). Clusterin expression levels were
      correlated with paclitaxel resistance in cervical cancer cell lines, and
      transfection of clusterin siRNA into HeLaS3 cells significantly decreased their
      resistance to paclitaxel (P<0.05). CONCLUSION: Our finding that clusterin
      expression was significantly higher in cervical cancer than in normal cervical
      tissues suggests that clusterin may confer paclitaxel resistance in cervical
      cancer cells.

PMID- 16890275
TI  - Is systematic scalene node biopsy in pretreatment evaluation of locally advanced
      cervical carcinoma necessary? Systematic dissection and histopathology of left
      scalene node biopsies in patients with locally advanced cervical carcinoma.
AB  - OBJECTIVE: Cervical carcinomas mainly spread via lymphatics, stepwise from pelvic
      to aortic and scalenic lymph nodes. Metastatic nodes are the major prognostic
      factor in this disease. When scalenic nodes are involved, cervical cancer is
      considered to be disseminated. Since there is a major discrepancy in reported
      percentages of metastatic scalene nodes in the literature (0 to 50%), we
      proceeded to systematic pretreatment scalene node biopsy and then evaluated the
      validity of this procedure. METHODS: From January 1998 to May 2003, 72 patients
      with locally advanced cervical carcinoma and no suspicious paraaortic or scalenic
      nodes (respectively on magnetic resonance imaging and clinically) had a
      systematic surgical pretreatment lymph node evaluation (retroperitoneal
      laparoscopic infrarenal paraaortic lymph node dissection and left scalenic lymph
      node biopsy). Scalene biopsy was examined using hematoxylin/eosin stain and
      immunohistochemistry (KL1 antibodies). RESULTS: Among the 72 patients, 20 were
      stage IB2, 4 were IIA, 14 were IIB, 4 were IIIA, 27 were IIIB, 1 was IVA and 2
      had a recurrent cervical carcinoma. Fourteen women had histologically confirmed
      paraaortic metastases (11 macroscopic, 3 microscopic). No metastatic involvement
      of the scalene nodes was detected. Fifteen patients developed a recurrence within
      12 months (3 to 19 months). None of the patients developed scalenic recurrence.
      CONCLUSION: Left scalene node biopsy does not appear to be mandatory in routine
      pretherapeutic lymph node evaluation of patients with advanced cervical carcinoma
      and no clinical suspicious nodes. It may be useful to prove disseminated disease
      in patients with suspicious clinical nodes or hot spots on PET-scan, if fine
      needle biopsy is unconclusive.

PMID- 16890276
TI  - Indications for primary and secondary exenterations in patients with cervical
      cancer.
AB  - OBJECTIVE: Fifty years after the introduction of exenterative surgery in
      gynecologic oncology, the indication for primary and secondary exenteration is
      controversially discussed in cervical cancer patients. In addition, the term
      "palliative exenteration" is not precisely defined. We evaluate the role of
      primary exenteration in patients with stage IVA cervical cancer and the role of
      secondary palliative exenteration. METHODS: The study retrospectively analyzed
      surgical and oncologic data of 55 patients who underwent exenterative surgery in
      the Department of Gynecology at the University of Jena between February 1998 and
      January 2004. Primary surgery was performed in 20 patients with laparoscopically
      confirmed stage IVA cervical cancer, while 35 patients with recurrent cervical
      cancer underwent secondary exenteration. Fifty-one had total, 3 posterior and 1
      anterior exenteration. Survival was analyzed in relation to the patient's age,
      indication (primary versus secondary, curative versus palliative), previous
      therapy (operation, radiation, chemotherapy, radiochemotherapy), histology,
      resection margins, pelvic nodal involvement, time interval from primary therapy
      to recurrence, type of exenteration and adjuvant therapy. Early and late
      postoperative complications as well as perioperative mortality were reviewed.
      RESULTS: The overall cumulative survival of all patients after exenteration was
      36.8% at 5 years with 52.5% in the primary group and 26.7% in the recurrent one
      (p=0.0472). Complications were noted in 56.9% of patients, most commonly fistulas
      or gastrointestinal complications. Operative mortality was 5.5%. Survival
      correlated significantly with the time interval between primary treatment and
      recurrence (within 1-2 years 16.8% five-year survival, 2-5 years 28%, >5 years
      83.2%, p=0.0105) as well as with curative or palliative intention (2-year
      survival rate of 60% in patients with curative intent, 10.5% in those with
      palliative intent, p=0.0001) and with tumor-free resection margins (2-year
      survival of 10.2% for positive margins, 5-year survival of 55.2% for negatives
      ones, p=0.0057). The age, the type of exenteration, the histologic type and the
      metastatic spread to pelvic lymph nodes had no significant influence on long-term
      survival. CONCLUSION: In patients with histopathologically confirmed stage IVA
      cervical cancer primary, exenteration is a valid alternative to primary
      chemoradiation. In patients with persistent or recurrent tumor limited to the
      pelvis, secondary exenteration should be offered in the absence of other
      therapeutic options. Palliative and curative attempts can best be differentiated
      by the resection margin status.

PMID- 16890277
TI  - The addition of extensive upper abdominal surgery to achieve optimal
      cytoreduction improves survival in patients with stages IIIC-IV epithelial
      ovarian cancer.
AB  - OBJECTIVES: To determine the survival impact of adding extensive upper abdominal
      surgical cytoreduction to standard surgical techniques for advanced ovarian
      cancer. METHODS: The records of all patients with stages IIIC-IV epithelial
      ovarian cancer who underwent primary surgery at our institution from 1998 to 2003
      were reviewed. The cohort was divided into 3 groups. Group 1 patients required
      extensive upper abdominal surgery, such as diaphragm peritonectomy/resection,
      resection of parenchymal liver or porta hepatis disease and/or splenectomy with
      or without distal pancreatectomy, to achieve optimal cytoreduction (residual
      disease<or=1 cm). Group 2 patients were optimally cytoreduced by standard
      surgical techniques, including hysterectomy, oophorectomy, omentectomy, and bowel
      resection. Group 3 patients were suboptimally cytoreduced. Primary outcome
      measures were response to primary chemotherapy, progression-free survival, and
      overall survival. RESULTS: The cohort of 262 patients was divided as follows:
      Group 1, 57 patients; Group 2, 122 patients; and Group 3, 83 patients. The median
      follow-up was 36 months (range, 1-94 months). Frequency of clinical complete
      response in Groups 1, 2, and 3 was 82%, 78%, and 57%, respectively. The median
      progression-free survival for Groups 1, 2, and 3 was 24, 23, and 11 months,
      respectively. Progression-free survival for Groups 1 and 2 were equivalent
      (P=0.53) and were significantly longer than for Group 3 (P<0.001). The median
      overall survival was 84 and 38 months for Groups 2 and 3, respectively, and had
      not been reached for Group 1 by 68 months. Patients in Group 1 had equivalent
      overall survival to patients in Group 2 (P=0.74) and improved survival over
      patients in Group 3 (P<0.001). Prognostic factors significant on multivariate
      analysis included stage, optimal status, and ascites. CONCLUSIONS: Patients
      requiring extensive upper abdominal procedures to achieve optimal cytoreduction
      demonstrated a similar initial response, progression-free survival, and overall
      survival to patients optimally cytoreduced by standard surgical techniques. The
      presence of bulky upper abdominal disease alone did not appear to indicate poor
      tumor biology. This initial maximal surgical effort was associated with improved
      survival in patients who would have otherwise been suboptimally cytoreduced.

PMID- 16890278
TI  - Acoustic features of palilalia: a case study.
AB  - While a number of authors have suggested that patients with palilalia typically
      show a tendency to repeat words or phrases with an increasing rate, others
      maintain that an accelerating speech rate is not essential. The present paper
      reports the results of an instrumental analysis of the reiterations in a 60-year
      old man with palilalia. Results indicate that there is not necessarily an
      increasing rapidity in palilalia. Duration of the repetition trains, duration of
      the pauses between the trains, and average number and average duration of the
      components within a train were variable but did not show a pattern indicative of
      a systematically increasing rate. The variation in the reiterations suggests that
      novel or varying motor processes are deployed to produce the elements in a
      sequence rather than an invariant motor program.

PMID- 16890280
TI  - Benthic recovery during open sea fish farming abatement in Western Mediterranean,
      Spain.
AB  - Fish farming is an important source of organic matter input in coastal waters,
      which contributes to eutrophication. In this study, the macrofaunal benthic
      community was studied after the cessation of fish farming with the aim of
      improving our understanding of benthic succession and sediment recovery in a
      marine ecosystem. The results showed that the best environmental variables for
      assessing organic pollution were acid-volatile sulfides (AVS) and redox
      potential. Succession and recovery was best explained by macrofaunal analysis
      based on community composition as well as on trophic groups. The patterns of
      recovery differed between each impacted station. For this reason, succession
      could not be accurately predicted due to the unique environmental parameters and
      the singular community functional structure of each location. The Azti Marine
      Benthic Index (AMBI) proved its validity for assessing pollution but did not
      distinguish between successional stages.

PMID- 16890281
TI  - Succession of macrofauna on macroalgal wrack of an exposed sandy beach: effects
      of patch size and site.
AB  - In this study, we used experimental manipulation of algal wrack to test
      hypotheses about influences on macrofaunal assemblages inhabiting the upper shore
      level of different sites along an exposed sandy beach. First, we hypothesized
      that decomposition of algal wrack depends on wrack patch size and site. With
      respect to macrofauna, we tested the hypotheses that (1) abundance of colonising
      individuals and species vary with wrack patch size, (2) succession (i.e. sequence
      of colonisation and species replacement) depends on time, and (3) as a result,
      macrofaunal assemblages associated with wrack patches vary with the patch size
      and time. We also predicted that responses could be different across sites
      because of their slightly different environmental conditions. The decomposition
      of wrack patches was similar in all sites and was dependent on wrack patch size.
      It was strongly influenced by time-specific environmental and/or biological
      factors. The pattern of colonisation, i.e. total number of species and
      individuals, varied among wrack patch sizes. Small patches had fewer species and
      individuals than medium and large patches. Nevertheless, pattern of colonisation
      varied among species, across sites and through time. Colonisation of wrack
      patches was rapid (i.e. within 3 days) for most species. There was some evidence
      to support the hypothesis that macrofaunal assemblages change in response to
      patch size and time.

PMID- 16890279
TI  - The role of left perisylvian cortical regions in spelling.
AB  - In order to examine the role of left perisylvian cortex in spelling, 13
      individuals with lesions in this area were administered a comprehensive spelling
      battery. Their spelling of regular words, irregular words, and nonwords was
      compared with that of individuals with extrasylvian damage involving left
      inferior temporo-occipital cortex and normal controls. Perisylvian patients
      demonstrated a lexicality effect, with nonwords spelled worse than real words.
      This pattern contrasts with the deficit in irregular word spelling, or regularity
      effect, observed in extrasylvian patients. These findings confirm that damage to
      left perisylvian cortex results in impaired phonological processing required for
      sublexical spelling. Further, degraded phonological input to orthographic
      selection typically results in additional deficits in real word spelling.

PMID- 16890282
TI  - Studies on the hemolytic activity of tentacle extracts of jellyfish Rhopilema
      esculentum Kishinouye: application of orthogonal test.
AB  - The present work is first reporting the hemolytic activity of venom from
      jellyfish Rhopilema esculentum Kishinouye extracted by different phosphate buffer
      solutions and incubated at different temperature according to the orthogonal test
      L6(1) x 3(6). Of the seven controllable independent variables, incubated
      temperature and phenylmethylsulfonyl fluoride (PMSF) had strongest effect on the
      hemolytic activity.

PMID- 16890283
TI  - Predisposition to therapy-related acute leukemia with balanced chromosomal
      translocations does not result from a major constitutive defect in DNA double
      strand break end joining.
AB  - The frequency of acute myeloid leukemia (AML) with balanced chromosomal
      translocations arising after anticancer therapy with DNA-damaging agents such as
      DNA topoisomerase II inhibitors has increased over the last two decades. However,
      factors that predispose to these therapy-related disorders are still poorly
      defined. It has been reported that DNA double-strand break (DSB) repair by the
      non-homologous end-joining (NHEJ) pathway is impaired in myeloid leukemia cells.
      This led us to hypothesize that therapy-related AML (t-AML) may result from
      individual differences in the repair of DSBs generated by the treatment. We show
      here that DSB repair is accurate, in vivo, in non-tumoral cells derived from
      patients who developed t-AML with t(9;11) or t(15;17) translocation after
      treatment for a first cancer with DNA topoisomerase II inhibitors. These results
      indicate that a major constitutive defect in the NHEJ pathway is unlikely to
      predispose to t-AML with balanced chromosomal translocations.

PMID- 16890284
TI  - B-CLL cells from lymph nodes express higher ZAP-70 levels than B-CLL cells from
      peripheral blood.

PMID- 16890285
TI  - Inefficacy of bortezomib therapy for CNS involvement of refractory multiple
      myeloma.

PMID- 16890286
TI  - Induction of complete remission in a patient with acute myeloid leukemia
      refractory to high-dose chemotherapy through treatment with 5-azacytidine.
AB  - For patients with acute myeloid leukemia refractory to intensive chemotherapy
      prognosis is very poor and treatment options are limited. 5-Azacytidine, a
      demethylating drug, is effective in the treatment of myelodysplastic syndromes
      when administered at a low-dose, subcutaneously. We report a case of a patient
      with AML refractory to induction chemotherapy as well as to two high-dose salvage
      regimens. The patient achieved CR through monotherapy with low-dose azacytidine.

PMID- 16890287
TI  - RAD51 homologous recombination repair gene haplotypes and risk of acute myeloid
      leukaemia.
AB  - Homologous recombination (HR) is one of the main pathways for the repair of DNA
      double strand breaks (DSBs). To investigate whether inherited variants in genes
      encoding proteins that repair DSBs by HR modulate acute myeloid leukaemia (AML)
      risk, we have examined the frequency of two variants in the 5' untranslated
      region (UTR) of RAD51 (RAD51 135 G>C and the RAD51 172 G>T) in a large case
      control study of acute myeloid leukaemia (AML). Inheritance of a RAD51 135 C
      allele was associated with a reduced risk of estimate for AML (odds ratio (OR)
      0.56, 95% confidence intervals (CI), 0.38-0.83), while the RAD51 172 T allele was
      not associated with AML. The RAD51 135 and 172 variants were in strong linkage
      disequilibrium, with three out of the four possible haplotypes being observed in
      the population. The protective effect associated with the RAD51 135 C allele was
      found to be associated with inheritance of the RAD51 135-172 C-G haplotype (cases
      3.9% versus controls 6.5%, OR 0.61, 95% CI 0.42-0.90). These data suggest that
      variants in the RAD51 HR gene may modulate genetic predisposition to AML.

PMID- 16890288
TI  - Aberrant methylation in pediatric myelodysplastic syndrome.
AB  - BACKGROUND: Aberrant methylation of gene promoter region is responsible for
      inappropriate gene silencing, and it has been associated to initiation and
      progression of cancer. Aberrant promoter methylation is frequently observed in
      adult patients with myelodysplastic syndrome (MDS), but in pediatric patients it
      has been poorly investigated. METHODS: We examined the promoter methylation
      status of 13 genes in bone marrow cells collected at diagnosis of 21 pediatric
      patients with MDS (subtype RAEB or RAEB-t). For this analysis, we performed
      sodium bisulfite treatment of genomic DNA, followed by methylation specific PCR
      (MSP). RESULTS: In pediatric MDS samples, we observed two genes frequently
      methylated: CALCA was methylated in 85.7% (18/21) of the analyzed samples and
      CDKN2B in 50% (6/12). CONCLUSIONS: Our findings indicate that CALCA and CDKN2B
      are frequently methylated in pediatric MDS. It suggests that aberrant methylation
      in pediatric MDS seems to be similar to adult MDS, thus pediatric patients could
      be also benefited with treatment using demethylating agents.

PMID- 16890289
TI  - Characterization of three distinct CpG oligonucleotide classes which differ in
      ability to induce IFN alpha/beta activity and cell proliferation in Atlantic
      salmon (Salmo salar L.) leukocytes.
AB  - Oligodeoxynucleotides (ODNs) containing unmethylated CpG dinucleotides within
      specific sequence contexts (CpG motifs) are in humans divided into three distinct
      classes (A, B and C). The CpG ODNs, like baterial DNA, are recognized by the
      vertebrate immune system and are known to stimulate immune responses. The
      characterization of the different classes is based on their structure and
      biological activity. In this study, we report the effects of these classes of CpG
      ODNs as they are defined in humans on IFN alpha/beta production and cell
      proliferation in Atlantic salmon spleen, head kidney and blood leukocytes. These
      studies revealed that CpG A together with CpG C are strong inducers of IFN
      alpha/beta in spleen and head kidney leukocytes, whilst CpG B and CpG C had the
      highest capacity to stimulate cell proliferation in all three cell populations.
      These findings are the first to establish that the effects of the different CpG
      classes are comparable between fish and man.

PMID- 16890290
TI  - Impact of pretilachlor herbicide and pyridaphenthion insecticide on aquatic
      organisms in model streams.
AB  - To detect the impact of pesticides on aquatic organisms, model streams (3m wide,
      20 m long) were established in paddy field in Japan. More than 100 species of
      aquatic organisms were generated in the model streams. Field tests with
      pretilachlor herbicide and pyridaphenthion insecticide were carried out in the
      streams for 3 yr (2001-2003). Exposure of pretilachlor (max. 0.382 mg/L) showed
      little density changes in algae with a Bray-Curtis percent similarity in the
      range 81.6-93.3% for algae. Exposure to high concentrations (>0.1mg/L) of
      pyridaphenthion produced visible density reductions in Cladocera zooplankton
      species. Reduction of individual aquatic insects in the model streams by
      pyridaphenthion caused an increase of chlorophyll a greater than that of the
      control streams. The pesticides used showed no substantial differences in the
      ecosystems of model streams exposed to maximum environmental concentrations
      (e.g., 0.01 mg/L) detected in real rivers.

PMID- 16890292
TI  - Multifunctional regulators of cell growth are differentially expressed in anergic
      murine B cells.
AB  - Defective anergy is a major cause of failed tolerance and is amenable to
      therapeutic manipulation. To better define the molecular basis of anergy in B
      cells tolerized by matrix self-antigen, we used complementary approaches of
      representational difference analysis (RDA) and microarray to identify genes
      differentially transcribed in anergic as compared to non-tolerant B cells
      isolated from a well-characterized murine autoantibody transgenic model. Forty
      RDA clones representing 16 genes were isolated from receptor-stimulated B cells
      and independently confirmed as differentially expressed in tolerant cells using
      custom microarray, dot blotting and/or quantitative PCR. Differential expression
      was conserved in tolerant cells from two different transgenic founder lineages
      and from two genetically disparate backgrounds. Prominent among recovered gene
      fragments were genes encoding multifunctional proteins not previously implicated
      in B cell biology, but with roles in biologic processes fundamental to the
      tolerance phenotype, including cell growth, proliferation and differentiation.
      RDA also identified a novel transcript not previously reported in nucleic acid
      databases. To further explore dependence on receptor stimulation and to identify
      additional genes, commercial oligonucleotide arrays were probed with labeled B
      cell transcripts and analyzed for genes differentially expressed in resting as
      well as stimulated cells and in both B6 and MRL mouse strains. Arrays identified
      differential expression of a subset of RDA genes as well as 46 additional genes,
      including subsets engaged in signal transduction, transcriptional regulation,
      cell growth and apoptosis. Immunoblotting confirmed differential protein
      expression for galectin-3 and galectin-1, two interactive members of the galectin
      family, suggesting a novel role for galectins as regulators of immune tolerance.

PMID- 16890293
TI  - Decavanadate interactions with actin: inhibition of G-actin polymerization and
      stabilization of decameric vanadate.
AB  - Decameric vanadate species (V10) inhibit the rate and the extent of G-actin
      polymerization with an IC50 of 68+/-22 microM and 17+/-2 microM, respectively,
      whilst they induce F-actin depolymerization at a lower extent. On contrary, no
      effect on actin polymerization and depolymerization was detected for 2mM
      concentration of "metavanadate" solution that contains ortho and metavanadate
      species, as observed by combining kinetic with (51)V NMR spectroscopy studies.
      Although at 25 degrees C, decameric vanadate (10 microM) is unstable in the assay
      medium, and decomposes following a first-order kinetic, in the presence of G
      actin (up to 8 microM), the half-life increases 5-fold (from 5 to 27 h). However,
      the addition of ATP (0.2mM) in the medium not only prevents the inhibition of G
      actin polymerization by V10 but it also decreases the half-life of decomposition
      of decameric vanadate species from 27 to 10h. Decameric vanadate is also
      stabilized by the sarcoplasmic reticulum vesicles, which raise the half-life time
      from 5 to 18h whereas no effects were observed in the presence of
      phosphatidylcholine liposomes, myosin or G-actin alone. It is proposed that the
      "decavanadate" interaction with G-actin, favored by the G-actin polymerization,
      stabilizes decameric vanadate species and induces inhibition of G-actin
      polymerization. Decameric vanadate stabilization by cytoskeletal and
      transmembrane proteins can account, at least in part, for decavanadate toxicity
      reported in the evaluation of vanadium (V) effects in biological systems.

PMID- 16890294
TI  - Magnetic resonance microscopy of spinal cord injury in mouse using a miniaturized
      implantable RF coil.
AB  - A magnetic resonance neuroimaging method is described for high-resolution imaging
      of spinal cord injury in live mouse. The method is based on a specially designed
      radio frequency coil system formed by a combination of an implantable coil and an
      external volume coil. The implantable coil is a 5 mm x 10 mm rectangular design
      with a 9.1 pF capacitor and 22 gauge copper wire and optimal for surgical
      implantation over the cervical or thoracic spine. The external volume coil is a
      standard birdcage resonator. The coils are inductively overcoupled for imaging
      the spinal cord at 9.4 T magnetic field strength. The inductive overcoupling
      provides flexibility in tuning the resonant frequency and matching the impedance
      of the implanted coil remotely using the tuning and matching capabilities of the
      volume coil. After describing the implementation of the imaging setup, in vivo
      data are gathered to demonstrate the imaging performance of the coil system and
      the feasibility of performing MR microscopy on injured mouse spinal cord.

PMID- 16890291
TI  - Development of structure and function in the infant brain: implications for
      cognition, language and social behaviour.
AB  - Recent advances in cognitive neuroscience have allowed us to begin investigating
      the development of both structure and function in the infant brain. However,
      despite the rapid evolution of technology, surprisingly few studies have examined
      the intersection between brain and behaviour over the first years of life. Even
      fewer have done so in the context of a particular research question. This paper
      aims to provide an overview of four domains that have been studied using
      techniques amenable to elucidating the brain/behaviour interface: language, face
      processing, object permanence, and joint attention, with particular emphasis on
      studies focusing on early development. The importance of the unique role of
      development and the interplay between structure and function is stressed
      throughout. It is hoped that this review will serve as a catalyst for further
      thinking about the substantial gaps in our understanding of the relationship
      between brain and behaviour across development. Further, our aim is to provide
      ideas about candidate brain areas that are likely to be implicated in particular
      behaviours or cognitive domains.

PMID- 16890295
TI  - Improved version of the printed circuit board (PCB) modular multi-channel
      microdrive for extracellular electrophysiological recordings.
AB  - The modular multi-channel PCB microdrive was described some years ago, since then
      several improvements were introduced while using these drives. Utilizing several
      years of experience with the original PCB microdrive we redesigned it to improve
      its stability and usability. The application of the printed circuit board
      technology and the extensive use of flexible fused silica capillaries for
      fabrication of the microdrive are described in detail. The improved design led to
      a low cost and light-weight multi-channel microdrive with outstanding modularity
      for extracellular field, single unit or multiunit tetrode recording up to 64/128
      channels.

PMID- 16890296
TI  - Psychological distress in migrants in Australia over 50 years old: a longitudinal
      investigation.
AB  - BACKGROUND: Although it is a well-known fact that migration is a risk factor
      contributing to psychopathology, little is known in migrants who migrated in
      their old age. The present study examined whether origin of countries and visa
      types predicted psychological distress over a period of 1 year and whether their
      association changed after factors in health, social roles, cohort effect and
      social support were adjusted. METHODS: A nationwide representative sample of 431
      migrants who aged 50 and above were interviewed in 2000-2001 and 359 of them were
      re-interviewed 1 year after the baseline assessment. 12-item General Health
      Questionnaire (GHQ-12) was used measure psychological distress and a series of
      questions regarding socio-demographic characteristics (age, gender, living
      alone), days in Australia, origin of countries, visa types, health, social role,
      cohort effect, and social support were also included. RESULTS: GHQ-12 scores did
      deteriorate over a period of 1 year among older migrants to Australia. In
      multiple regression analyses, origin of countries and visa types were significant
      predictors of future GHQ-12 scores. Baseline GHQ-12 scores, age, gender, living
      alone, days in Australia, poor self-rated health, the presence of heart disease,
      diabetes, and asthma, being a student or economically inactive, widowhood or
      divorce, as well as education were also significant predictors of GHQ-12 scores
      at 1-year follow-up. CONCLUSIONS: The status of refugees predicts future
      psychological distress in older migrants even when other known correlates of
      psychological distress are controlled.

PMID- 16890297
TI  - Insulin-like growth factor-I enhances the biological activity of brain-derived
      neurotrophic factor on cerebrocortical neurons.
AB  - Insulin-like growth factor (IGF)-I and brain-derived neurotrophic factor (BDNF)
      act within the brain to enhance neuronal survival and plasticity. We extend these
      findings by showing that the presence of both neurotrophins is required to
      depress the rise in intracellular Ca2+ caused by glutamate in primary cultures of
      cerebrocortical neurons. IGF-I enhanced expression of BDNF receptors (Trk-B) and
      increased the ability of BDNF to induce ERK1/2 phosphorylation. This IGF-I
      induced increase in BDNF responsiveness describes a new interaction between these
      peptides in the brain.

PMID- 16890298
TI  - DNA immunization with 2C FMDV non-structural protein reveals the presence of an
      immunodominant CD8+, CTL epitope for Balb/c mice.
AB  - Outbreaks of foot and mouth disease virus (FMDV) have devastating economic
      consequences in affected areas. The presence of multiple serotypes and virus
      variants makes vaccination complicated. A better understanding of protective
      immune mechanisms may help in development of novel vaccines with cross protective
      capacity. While much attention has been devoted to humoral responses to FMDV,
      less is known about the role of cell-mediated responses in protective immunity.
      Predictions of potential CTL epitopes by two different computer algorithms
      identified the viral 2C protein as containing a potential murine H2-Kd CTL
      epitope located in its amino-terminal half. DNA vaccination of mice with a
      plasmid expressing the 2C protein and a fragment thereof confirmed that this was
      indeed a CTL epitope, as shown by interferon gamma (IFN-gamma) induction in CD8+,
      CD44(hi) splenocytes after in vitro stimulation with peptides containing the
      amino acid sequence KYKDAKEWL, predicted for the CTL epitope. A peptide with the
      variant sequence KYKEAKEWL induced similar responses, indicating tolerability
      towards a conservative substitution at the altered residue. Virus infection
      likewise induced a measurable CTL response against KYKDAKEWL, although less clear
      due to a higher background of IFN-gamma production in splenocytes from infected
      mice. Challenge of vaccinated mice showed that the CTL response induced by the 2C
      protein was not protective, since viremia and mortality were unaffected by
      vaccination. The implications for vaccine development are discussed in the
      context of cross-serotype reactive responses.

PMID- 16890299
TI  - C-fos induction in forebrain areas of two different visual pathways during
      consolidation of sexual imprinting in the zebra finch (Taeniopygia guttata).
AB  - Two forebrain areas in the hyperpallium apicale and in the lateral nidopallium of
      isolated male zebra finches are highly active (2-deoxyglucose technique) on
      exposure to females for the first time, that is first courtship. These areas also
      demonstrate enhanced neuronal plasticity when screened with c-fos
      immunocytochemistry. Both are areas involved in the processing of visual
      information conveyed by the two major visual pathways in birds, strengthening our
      hypothesis that courtship in the zebra finch is a visually guided behaviour.
      First courtship and chased birds show enhanced c-fos induction in the
      hyperpallial area, which could represent neuronal activity reflecting changes in
      the immediate environment. The enhanced expression of fos in first courtship
      birds in lateral nidopallial neurons indicates imminent long-lasting changes at
      the synaptic level that form the substrate for imprinting, a stable form of
      learning in birds.

PMID- 16890300
TI  - BALB/c mice: low sociability and other phenotypes that may be relevant to autism.
AB  - Low sociability is one of the most prominent and disabling symptoms of autism.
      The biology of sociability is not well understood, and there is no available
      treatment that adequately improves social functioning in most autistic patients.
      The development of animal models of reduced sociability can aid in the
      elucidation of the biology of social behaviors, and may ultimately shed light on
      the biology of autism. This paper will review evidence that mice of the BALB/c
      inbred strain show relatively low levels of social interaction in various
      settings and across various stages of development, including male-male
      interactions, female-female interactions, male-female sexual interactions, and
      parenting behaviors. Taken together, this evidence suggests a generally low level
      of sociability in BALB/c mice that may be relevant to autism. BALB/c mice also
      show other phenotypes with possible relevance to autism, including relatively
      high levels of anxiety and aggressive behaviors, large brain size,
      underdevelopment of the corpus callosum, and low levels of brain serotonin.
      Further research is needed to determine the relationship among these BALB/c
      phenotypes, and to determine their possible relevance to autism. In conclusion,
      the BALB/c inbred strain may be a useful animal model for identifying genes and
      neurobiological pathways involved in autism-related phenotypes.

PMID- 16890301
TI  - Lidocaine inactivation of the ventral pallidum affects responding for brain
      stimulation reward more than it affects the stimulation's reward value.
AB  - The ventral pallidum (VP) supports self-stimulation and has anatomical
      connections that suggest it could be linked to medial forebrain bundle (MFB) self
      stimulation. Dorsal VP appears to be more related to dorsal striatopallidum and
      thus to cognitive control of movement, while ventral VP appears to be more
      related to linking motivation to action. In this study we challenged MFB self
      stimulation by temporarily inactivating dorsal and ventral VP. We assessed
      changes in performance capacity and stimulation reward value using the rate
      frequency curve shift paradigm. VP inactivation, especially in the ventral aspect
      of the VP ipsilateral to the stimulation site, was more likely to substantially
      impair maximum response rate than to affect the frequency required to maintain
      half-maximal responding. These effects were transient, typically disappearing
      within 20 min following inactivation. Contralateral inactivation was relatively
      ineffective and bilateral inactivation was surprisingly less effective than
      ipsilateral inactivation alone, although bilaterally symmetric injection sites
      were largely confined to the dorsal VP. The fact that inactivation-induced
      changes in maximum response rate were more prominent than changes in the
      frequency required to maintain half-maximal responding suggests a role for the
      ventral VP in linking reward to responding rather than detecting or computing
      reward value.

PMID- 16890302
TI  - Gene disruptions demonstrate independent roles for the four falcipain cysteine
      proteases of Plasmodium falciparum.
AB  - Erythrocytic stages of the malaria parasite Plasmodium falciparum express four
      related papain-family cysteine proteases, termed falcipains. Falcipain-2 and
      falcipain-3 are food vacuole hemoglobinases, but determination of the specific
      roles of these and other falcipains has been incomplete. To better characterize
      biological roles, we attempted disruption of each falcipain gene in the same
      strain (3D7) of P. falciparum. Disruption of falcipain-1, falcipain-2, and
      falcipain-2' was achieved. In each case knockouts multiplied at the same rate as
      wild-type parasites. The morphologies of erythrocytic falcipain-1 and falcipain
      2' knockout parasites were indistinguishable from those of wild-type parasites.
      In contrast, consistent with previous results, falcipain-2 knockout trophozoites
      developed swollen, hemoglobin-filled food vacuoles, indicative of a block in
      hemoglobin hydrolysis and were, compared to wild-type parasites, twice as
      sensitive to cysteine protease inhibitors and over 1000 times more sensitive to
      an aspartic protease inhibitor. The falcipain-3 gene could not be disrupted, but
      replacement with a tagged functional copy was readily achieved, strongly
      suggesting that falcipain-3 is essential to erythrocytic parasites. Our data
      suggest key roles for falcipain-2 and falcipain-3 in the development of
      erythrocytic malaria parasites and a complex interplay between P. falciparum
      cysteine and aspartic proteases.

PMID- 16890303
TI  - Characterization of the DNA-binding properties and the transactivation activity
      of Schistosoma mansoni nuclear receptor fushi tarazu-factor 1alpha (SmFTZ
      F1alpha).
AB  - A FTZ-F1-related orphan nuclear receptor SmFTZ-F1alpha was previously identified
      from Schistosoma mansoni. The deduced SmFTZ-F1alpha protein contains a highly
      conserved DNA binding domain (DBD, C domain), a less conserved ligand binding
      domain (LBD, E domain) and three highly variable regions, the N-terminal A/B
      domain (108 aa), a large hinge region (D domain, 1027 aa) and an F domain (220
      aa). Herein, we characterize the DNA binding properties and the transactivation
      activity of SmFTZ-F1alpha. In in vitro assays, SmFTZ-F1alpha bound as a monomer
      to a response element (FF1RE: TCAAGGTCA) recognized by mammalian steroidogenic
      factor 1 (SF-1), and to related sequences (p14: TTAAGGTCA and SmFF1a-2:
      CGAAGGTCA) derived from known schistosome gene promoters. Competition assays with
      p14 oligonucleotides containing a single mutation at each nucleotide position
      defined the optimum DNA sequence required for SmFTZ-F1alpha binding. The optimal
      consensus sequence for SmFTZ-F1alpha binding is TN(A/G)AGGTC(A/G) (N: any base).
      This sequence is similar but not identical to the SF-1 response element (SFRE)
      consensus sequence [(T/C)CAAGG(T/C)C(A/G)]. By performing yeast one-hybrid
      assays, the ability of SmFTZ-F1alpha to bind productively to a p14-derived 9-base
      pair sequence was demonstrated in vivo. The ability of the full-length SmFTZ
      F1alpha to transactivate reporter gene expression was shown to be A/B domain
      dependent in a yeast system. In addition, the hinge region contained an
      unexpected activation function (AF) domain, termed AF-3, while no transactivation
      activity was detected within the E/F domain. This AF-3 region (from aa 982 to aa
      1110) revealed a strong autonomous transactivation activity, which was masked
      when it was present in the full-length SmFTZ-F1alpha. Taken together, our results
      suggest that SmFTZ-F1alpha possesses the characteristic DNA binding specificity
      of FTZ-F1 subfamily members and the capacity to transactivate a reporter gene.

PMID- 16890304
TI  - Reconsidering the Caregiving Stress Appraisal scale: validation and examination
      of its association with items used for assessing long-term care insurance in
      Japan.
AB  - The Caregiving Stress Appraisal (CSA) scale is a simple scale for measuring
      family caregiver stress. However, information on its validity and association
      with new social welfare systems in Japan is inadequate. The purpose of the
      present study is to examine the criterion validity of the CSA and to explore its
      association with the variables used for assessing long-term care insurance in
      Japan. In the present study, 219 family caregivers completed a self-administered
      questionnaire. Of these, 50 and 202 caregivers were used for the analysis of the
      criterion validity and construct validity, respectively. The CSA, the Japanese
      version of the Zarit Burden Interview (J-ZBI), the Center for Epidemiological
      Studies-Depression (CES-D), and the items used for assessing long-term care
      insurance in Japan were used for the analyses. The results revealed that the CSA
      had significant correlations with the J-ZBI and the CES-D. Despite the small
      sample size, the CSA had significant correlations with the items used for
      assessing long-term care insurance in Japan. These results suggest sufficient
      criterion and construct validity of the CSA for the future study.

PMID- 16890306
TI  - Acute myocarditis and myocardial infarction induced by Paraphenylenediamine
      poisoning. Interest of angiocoronarography.
AB  - We present 2 cases of myocardial damage induced by Paraphenylenediamine (PPD)
      poisoning in young patients without any history of cardiovascular disease. ECG
      findings revealed the presence of localized ST segment elevation in precordial
      leads (V1-V4) in the first case and (V3-V6) in the second associated to an
      increase of the serum troponine T level at 23 ng/ml (case 1) and 29.7 ng/ml (case
      2). The transthoracic echocardiography was in favour of diffuse myocarditis in
      the first case and of localized myocarditis or septo-apical myocardial infarction
      in the second. The angiocoronarography performed for the first time in the second
      case conclude on a septo-apical hypokinesia of the left ventricular resulting of
      a coronary spasm of the anterior interventricular artery.

PMID- 16890305
TI  - Restrictive cardiomyopathy with atrioventricular conduction block resulting from
      a desmin mutation.
AB  - BACKGROUND: According to the predominant view, desmin mutations cause dilated
      cardiomyopathy (DCM). We evaluated a family with restrictive cardiomyopathy (RCM)
      associated with a novel desmin mutation and reviewed recent reports regarding the
      frequency of RCM in patients with desmin myopathy. METHODS: Cardiovascular
      examination was performed in three affected and five at-risk members of a family
      from Poland, histopathologic study of skeletal muscle biopsy was done in a single
      patient, and functional analysis of mutant desmin protein was carried out in
      cultured cells. RESULTS: Cardiovascular assessment led to the diagnosis of RCM in
      affected family members. Histopathological study of skeletal muscle biopsy
      revealed features characteristic of desmin myopathy. A novel desmin E413K
      mutation was identified in each affected family member, but not unrelated
      controls. The pathogenicity of the E413K mutation was confirmed in transfected
      cell cultures showing inability of mutant desmin to form a cellular filamentous
      network or support a pre-existing network formed by other intermediate filaments.
      Three-dimensional modeling and electrostatic calculations indicated that the
      E413K mutation located in a functionally unique domain of desmin molecule
      potentially disrupts intramolecular interactions. Analysis of previously reported
      observations indicates that RCM in desminopathy patients may be as frequent as
      DCM. CONCLUSIONS: A novel E413K mutation in desmin caused autosomal dominant RCM
      rather than DCM. The location of the E413K mutation at a highly conserved end of
      the alpha-helical rod domain may be related to the phenotypic differences from
      the previously described DCM-associated desmin mutations. Functional and
      structural analyses of mutant desmin allowed to identify likely pathogenic
      mechanisms.

PMID- 16890307
TI  - Diagnosis of vasospastic angina: comparison of hyperventilation and cold-pressor
      stress echocardiography, hyperventilation and cold-pressor stress coronary
      angiography, and coronary angiography with intracoronary injection of
      acetylcholine.

PMID- 16890308
TI  - Coronary artery dissection following angioplasty detected by multi-detector row
      computed tomography: evaluation using the Plaque Map system.

PMID- 16890309
TI  - Long-term clinical outcome of patients treated with beta-brachytherapy in routine
      clinical practice.
AB  - BACKGROUND: Only limited data exist regarding the long-term efficacy of beta
      brachytherapy (beta-VBT) in routine clinical practice and the impact of the
      prolonged (>6 months) combined antiplatelet therapy after beta-VBT. Our aim is to
      examine the long-term clinical efficacy of routine beta brachytherapy (beta-VBT)
      followed by indefinite administration of combined antiplatelet therapy in
      patients at high restenotic risk. METHODS: Sixty-one patients with 65 lesions [de
      novo: 41, in-stent restenotic (ISR): 24] underwent intracoronary beta-VBT and
      were followed prospectively. All patients received indefinite administration of
      aspirin and clopidogrel, underwent routine angiography 6 months later and were
      followed-up clinically for 43.7 months (range: 32 to 52 months). RESULTS: Acute
      success was achieved in 60/61 (98.4%) patients. Lesion length was 36.1 (+/-17.6)
      mm for the de novo and 22.0 (+/-9.8) mm for the ISR (p=0.001). Stents were
      implanted in 35/41 de novo and 7/24 ISR lesions (p<0.01). Six-month binary
      restenosis after successful beta-VBT was 35.9% (23/64). During follow-up patients
      with de-novo lesions who received a new stent during index procedure had a higher
      incidence of major cardiac events than patients with ISR lesions without a new
      stent (log rank test, p=0.02). Acute and late thrombotic events were reported at
      6 patients, all with de novo lesions and stent implantation. CONCLUSIONS: Beta
      VBT plus stenting in de novo lesions is related to an unacceptable high rate of
      thrombotic complications and clinical restenosis despite prolonged administration
      of combined antiplatelet therapy. Brachytherapy remains a reasonable option for
      patients with ISR lesions until full data from large randomized trials comparing
      drug eluting stents with brachytherapy are available.

PMID- 16890310
TI  - Giant right atrial aneurysm: case report.
AB  - A 15-month-old boy with atrial fibrillation was found to have gross cardiomegaly
      on a chest radiography; further evaluation by echocardiography showed a giant
      right atrial aneurysm which is in the form of a cyst like lesion. The patient
      underwent successful surgical reduction of the right atrium converting his heart
      rhythm to normal. The operative measure was taken to prevent thrombus formation
      in the right atrium and lower the risk of atrial arrhythmias. The morphologic
      features of the resected atrial tissue showed a thin wall with a central aneurysm
      and focal endocardial fibrosis without inflammatory response consistent with a
      diagnosis of idiopathic dilatation of the right atrium.

PMID- 16890311
TI  - An increased platelet-leukocytes interaction at the culprit site of coronary
      artery occlusion in acute myocardial infarction: a pathogenic role for "no
      reflow" phenomenon?
AB  - BACKGROUND: Distal protection devices have been shown to reduce the incidence of
      "no flow" phenomenon during primary percutaneous coronary intervention (PCI). So
      far, it has not been well clarified which mechanism is mainly involved in distal
      coronary protection. AIM: To investigate the activation state of leukocytes and
      platelets locally present within the blood from the site of coronary occlusion.
      METHODS: Ten patients with acute myocardial infarction (AMI) underwent primary
      PCI with an embolization protection device and aspiration catheter (PercuSurge
      GuardWire) were included. The following functional parameters: a) monocyte and
      neutrophils surface molecules; b) platelet surface activatory antigens; c)
      leukocytes-platelet conjugates were studied by flow cytometry in blood obtained
      from the site of coronary occlusion and from peripheral femoral artery. RESULTS:
      The leukocyte-platelet adhesion index was significantly higher in the aspirated
      blood at the site of coronary occlusion than in the peripheral arterial blood for
      both monocytes (0.226+/-0.04 vs. 0.084+/-0.01; p=0.004) and neutrophils (1.372+/
      0.3 vs. 0.524+/-0.1; p=0.02). Moreover, the volume of coaggregates exhibited a
      significant increase in coronary blood for both populations (p=0.02 for monocytes
      and for neutrophils). Interestingly, a significant up-regulation of the adhesive
      molecule CD18 was observed in coronary blood respect to systemic circulation
      either in monocytes (p=0.01) than in neutrophils (p=0.003). A significant up
      regulation of monocyte (HLA-DR) and neutrophil (CD66b) activatory molecules
      expression was also observed in the aspirated coronary compared to peripheral
      artery blood (p=0.02 and p=0.03 for HLA-DR and CD66b, respectively). CONCLUSIONS:
      These data indicate an increased leukocyte-platelet functional interaction in AMI
      at the site of plaque rupture relative to the systemic circulation, which may be
      one of the pathogenetic mechanisms responsible for myocardial "no-reflow"
      phenomenon.

PMID- 16890312
TI  - Sumatriptan provokes coronary artery spasm in patients with variant angina:
      possible involvement of serotonin 1B receptor.
AB  - BACKGROUND: Serotonin (5HT) can induce coronary artery spasm (CAS) in patients
      with variant angina (VA). We have previously reported that 5HT(1B) and 5HT(2A)
      receptors gene were expressed in human coronary arterial smooth muscle cells and
      that isolated coronary artery from a patient with VA showed the supersensitivity
      to sumatriptan (SMT), a 5HT(1B/1D) receptor agonist. The aim of the present study
      was to determine whether SMT can provoke CAS directly or indirectly through
      platelet aggregation in patients with VA. METHODS: We evaluated the effects of
      intracoronary infusion of graded concentrations of SMT on coronary arteries in 9
      patients, including 5 documented VA and 4 participants with atypical chest pain
      as control. RESULTS: SMT provoked CAS in all patients with VA. SMT could not
      induce CAS in control. SMT (10(-4) M) caused significant contractions (%diameter
      of baseline; median [interquartile range], 0 [0-18.4]% in VA, as compared with
      control (proximal segments; 92.6 [77.9-118.9]%, p<0.05 vs. VA, distal segments;
      92.9 [65.3-158.5]%, p<0.01 vs. VA). In control, minor dilation occurred at SMT
      concentration up to 10(-5) M. SMT could induce in vitro platelet aggregation
      neither in healthy subjects nor in patients with VA. CONCLUSIONS: These findings
      suggest that activation of 5HT(1B) receptor by SMT can induce CAS directly in
      patients with VA without platelet activation. This is the first report directly
      demonstrating the effect of 5HT(1B) receptor activation on human coronary
      arteries in vivo.

PMID- 16890313
TI  - Gatekeeping in health care.
AB  - We study the competitive effects of restricting direct access to secondary care
      by gatekeeping, focusing on the informational role of general practitioners
      (GPs). In the secondary care market there are two hospitals choosing quality and
      specialization. Patients, who are ex ante uninformed, can consult a GP to receive
      an (imperfect) diagnosis and obtain information about the secondary care market.
      We show that hospital competition is amplified by higher GP attendance but
      dampened by improved diagnosing accuracy. Therefore, compulsory gatekeeping may
      result in excessive quality competition and too much specialization, unless the
      mismatch costs and the diagnosing accuracy are sufficiently high. Second-best
      price regulation makes direct regulation of GP consultation redundant, but will
      generally not implement first-best.

PMID- 16890314
TI  - Aspiration rate following chemoradiation for head and neck cancer: an
      underreported occurrence.
AB  - BACKGROUND AND PURPOSE: We would like to assess the prevalence of aspiration
      before and following chemoradiation for head and neck cancer. PATIENTS AND
      METHODS: We reviewed retrospectively the Modified Barium Swallow (MBS) in 63
      patients who underwent concurrent chemotherapy and radiation for head and neck
      cancer. MBS was performed prior to treatment to determine the need for immediate
      gastrostomy tube placement. MBS was repeated following treatment to assess the
      safety of oral feeding prior to removal of tube feeding. All patients were cancer
      free at the time of the swallowing study. No patient had surgery. Dysphagia
      severity was graded on a scale of 1-7. Tube feedings were continued if patients
      were diagnosed to have severe aspiration (grade 6-7) or continued weight loss.
      Patients with abnormal swallow (grade 3-7) received swallowing therapy following
      MBS. RESULTS: Before treatment, there were 18 grade 1, 18 grade 2, 9 grade 3, 8
      grade 4, 3 grade 5, 3 grade 6, and 4 grade 7. Following chemoradiation, at a
      median follow-up of 2 months (1-10 months), one patient had grade 1, eight
      patients had grade 2, nine patients had grade 3, eight patients had grade 4, 13
      patients had grade 5, seven patients had grade 6, and 11 patients had grade 7.
      Six patients died from aspiration pneumonia (one before, three during, and two
      post-treatment), and did not have the second MBS. Overall, 37/63 (59%) patients
      developed aspiration, six of them (9%) fatal. If we excluded the 10 patients who
      had severe aspiration at diagnosis and the six patients who died from pneumonia,
      the prevalence of severe aspiration was 33% (21/63). CONCLUSIONS: Aspiration
      remained a significant morbidity following chemoradiation for head and neck
      cancer. Its prevalence is underreported in the literature because of its often
      silent nature. Diagnostic studies such as MBS should be part of future head and
      neck cancer prospective studies to assess the prevalence of aspiration, and for
      rehabilitation.

PMID- 16890315
TI  - Comparison of advanced irradiation techniques with photons for benign
      intracranial tumours.
AB  - BACKGROUND AND PURPOSE: The potential benefits and limitations of different
      radiation techniques (stereotactic arc therapy (SRS/T), intensity modulated
      radiotherapy (IMRT), helical tomotherapy (HT), Cyberknife and intensity-modulated
      multiple arc therapy (AMOA)) have been assessed using comparative treatment
      planning methods on twelve patients presenting with 'benign' brain tumours.
      MATERIALS AND METHODS: Plans for five acoustic neurinomas, five meningiomas and
      two pituitary adenomas were computed to generate dose distributions for all
      modalities using a common CT dataset to delineate planning target volume and
      organs at risk. RESULTS: HT, AMOA and IMRT resulted superior to SRS/T and
      Cyberknife for target coverage. For the first group V(95%) ranged from 98% to
      100%, minimum dose ranged from 91% to 96% and standard deviation from 0.84% to
      1.67%. For organs at risk all techniques respected planning objectives with a
      tendency of Cyberknife and SRS/T to better spare the brain stem and the healthy
      brain tissue (e.g., V(20Gy) of 2.0% and 2.3%, respectively, compared to 3.1-5.0%
      for the other techniques). AMOA is in general preferable to IMRT for all OARs.
      Conformity index (CI(95)) was better for HT and Cyberknife (both 1.8) and less
      for AMOA and IMRT (3.9 and 3.0, respectively). CONCLUSION: All techniques
      provided good OAR sparing and primarily differed in target coverage indices. For
      the class of tumours investigated in this report, HT, AMOA and IMRT had better
      target coverage with HT providing the best combination of indeces. Between AMOA
      and IMRT, target coverage was comparable and, considering organs at risk, AMOA
      was slightly preferable.

PMID- 16890317
TI  - Radiation-induced effects on gene expression: an in vivo study on breast cancer.
AB  - BACKGROUND AND PURPOSE: Breast cancer is diagnosed worldwide in approximately one
      million women annually and radiation therapy is an integral part of treatment.
      The purpose of this study was to investigate the molecular basis underlying
      response to radiotherapy in breast cancer tissue. MATERIAL AND METHODS: Tumour
      biopsies were sampled before radiation and after 10 treatments (of 2 Gray (Gy)
      each) from 19 patients with breast cancer receiving radiation therapy. Gene
      expression microarray analyses were performed to identify in vivo radiation
      responsive genes in tumours from patients diagnosed with breast cancer. The
      mutation status of the TP53 gene was determined by using direct sequencing.
      RESULTS AND CONCLUSION: Several genes involved in cell cycle regulation and DNA
      repair were found to be significantly induced by radiation treatment. Mutations
      were found in the TP53 gene in 39% of the tumours and the gene expression
      profiles observed seemed to be influenced by the TP53 mutation status.

PMID- 16890316
TI  - The prognostic value of pimonidazole and tumour pO2 in human cervix carcinomas
      after radiation therapy: a prospective international multi-center study.
AB  - BACKGROUND AND PURPOSE: Hypoxia adversely affects treatment outcome in human
      uterine cervical cancer. Here, we present the results of a prospective
      international multi-centre study evaluating the prognostic value of pre-treatment
      tumour oxygen partial pressure (pO(2)) and the hypoxia marker pimonidazole
      (pimo). MATERIALS AND METHODS: One hundred and twenty-seven patients with primary
      cervix cancer were entered. Pre-treatment tumour pO(2) measurements were
      obtained, and reported by the median tumour pO(2), the fraction of pO(2) values
      <or=10 mmHg (HP(10)), <or=5 mmHg (HP(5)) and <or=2.5 mmHg (HP(2.5)). Following
      intravenous pimonidazole administration, biopsies were taken, stained for
      pimonidazole adducts, and scored for the area of labelled tumour cells on a scale
      from 0 to 4. Treatment modalities were surgery (11%), radiotherapy (98%),
      chemotherapy (33%) and carbogen (14%). RESULTS: None of the hypoxia descriptors
      were statistically significant prognostic factors for loco-regional tumour
      control or overall survival when analyzed as continuous variables or divided by
      the sample median. By univariate analysis only tumour size and nodal status were
      significant prognostic factors for local control. Tumour size and FIGO stage were
      significant for overall survival. In a multivariate analysis stratified by
      centre, only tumour size above 5 cm and lower pre-treatment haemoglobin predicted
      poorer overall survival among FIGO stage, nodal involvement, tumour size, pre
      treatment haemoglobin dichotomized at 12 g/dl and pimo 1, pimo 4 and HP(5) as
      continuous variables. CONCLUSION: Neither Eppendorf nor pimonidazole should be
      dismissed based on the current results. However, further investigations are
      needed to readdress the hypotheses of the current study having optimized
      statistical designs, and a population of sufficient size treated more
      homogenously following rigorous protocols.

PMID- 16890318
TI  - Real-time PCR quantification of the AM-toxin gene and HPLC qualification of
      toxigenic metabolites from Alternaria species from apples.
AB  - Some Alternaria species are able to produce plant pathogenic as well as toxic
      metabolites. In both agriculture and the food industry it is important know if
      toxigenic Alternaria are present to rapidly employ the correct corrective
      actions. The purpose of this work was to establish a real-time PCR method, which
      can detect and quantify apple pathogenic and toxigenic Alternaria. An AM-toxin I
      primer set, which could recognize Alternaria DNA only, was designed by using
      primers complementary to the AM-toxin I gene. The method could detect small
      amounts of DNA (4 pg) and still obtain a large dynamic range (4 decades) without
      interference from apple material. Eight Alternaria isolates were analyzed for the
      presence of AM-toxin I gene and their production of secondary metabolites. Then
      analyses showed that all eight isolates contained the AM toxin gene and were able
      to produce the plant pathogenic tentoxin in addition to AM toxin I. The analyses
      also showed the production of tenuazonic acid, alternariols, Altenuene, altenusin
      and/or altertoxin I in pure culture. Analyses of inoculated apples showed that
      both the AM-toxin gene and alternariol monomethyl ether could be detected.
      Morphological analyses suggested that the eight Alternaria strains, though they
      all carried the AM toxin genes, probably belong to different but closely related
      un-described Alternaria taxa in the A. tenuissima species-group based on
      morphological and chemical differences.

PMID- 16890319
TI  - Under the influence of the active deodorant ingredient 4-hydroxy-3-methoxybenzyl
      alcohol, the skin bacterium Corynebacterium jeikeium moderately responds with
      differential gene expression.
AB  - A 70mer oligonucleotide microarray was constructed to analyze genome-wide
      expression profiles of Corynebacterium jeikeium, a skin bacterium that is
      predominantly present in the human axilla and involved in axillary odor
      formation. Oligonucleotides representing 100% of the predicted coding regions of
      the C. jeikeium K411 genome were designed and spotted in quadruplicate onto epoxy
      coated glass slides. The quality of the printed microarray was demonstrated by co
      hybridization with fluorescently labeled cDNA probes obtained from exponentially
      growing C. jeikeium cultures. Accordingly, genes detected with different
      intensities resulting in log(2) transformed ratios greater than 0.8 or smaller
      than -0.8 can be regarded as differentially expressed with a confidence level
      greater than 99%. In an application example, we measured global changes of gene
      expression during growth of C. jeikeium in the presence of different
      concentrations of the deodorant component 4-hydroxy-3-methoxybenzyl alcohol that
      is active in preventing body odor formation. Global expression profiling revealed
      that low concentrations of 4-hydroxy-3-methoxybenzyl alcohol (0.5 and 2.5mg/ml)
      had almost no detectable effect on the transcriptome of C. jeikeium. A slightly
      higher concentration of 4-hydroxy-3-methoxybenzyl alcohol (5mg/ml) resulted in
      differential expression of 95 genes, 86 of which showed an enhanced expression
      when compared to a control culture. Besides many genes encoding proteins that
      apparently participate in transcription and translation, the drug resistance
      determinant cmx and the predicted virulence factors sapA and sapD showed
      significantly enhanced expression levels. Differential expression of relevant
      genes was validated by real-time reverse transcription PCR assays.

PMID- 16890320
TI  - Cell delivery in regenerative medicine: the cell sheet engineering approach.
AB  - Recently, cell-based therapies have developed as a foundation for regenerative
      medicine. General approaches for cell delivery have thus far involved the use of
      direct injection of single cell suspensions into the target tissues.
      Additionally, tissue engineering with the general paradigm of seeding cells into
      biodegradable scaffolds has also evolved as a method for the reconstruction of
      various tissues and organs. With success in clinical trials, regenerative
      therapies using these approaches have therefore garnered significant interest and
      attention. As a novel alternative, we have developed cell sheet engineering using
      temperature-responsive culture dishes, which allows for the non-invasive harvest
      of cultured cells as intact sheets along with their deposited extracellular
      matrix. Using this approach, cell sheets can be directly transplanted to host
      tissues without the use of scaffolding or carrier materials, or used to create in
      vitro tissue constructs via the layering of individual cell sheets. In addition
      to simple transplantation, cell sheet engineered constructs have also been
      applied for alternative therapies such as endoscopic transplantation,
      combinatorial tissue reconstruction, and polysurgery to overcome limitations of
      regenerative therapies and cell delivery using conventional approaches.

PMID- 16890321
TI  - Manipulation of hydrogel assembly and growth factor delivery via the use of
      peptide-polysaccharide interactions.
AB  - The design of materials in which assembly, mechanical response, and biological
      properties are controlled by protein-polysaccharide interactions could provide
      materials that mimic the biological environment and find use in the delivery of
      growth factors. In the investigations reported here, a heparin-binding, coiled
      coil peptide, PF4 ZIP, was employed to mediate the assembly of heparinized
      polymers. The heparin-binding affinity of this peptide was compared with that of
      other heparin-binding peptides (HBP) via heparin-sepharose chromatography and
      surface plasmon resonance (SPR) experiments. Results from these experiments
      indicate that PF4 ZIP demonstrates a higher heparin-binding affinity and heparin
      association rate when compared to the heparin-binding domains of antithrombin III
      (ATIII) and heparin-interacting protein (HIP). Viscoelastic hydrogels were formed
      upon the association of PF4 ZIP-functionalized star poly(ethylene glycol) (PEG
      PF4 ZIP) with low-molecular-weight heparin-functionalized star PEG (PEG-LMWH).
      The viscoelastic properties of the hydrogels can be altered via variations in the
      ratio of LMWH to PF4 ZIP. bFGF release from these gels have also been
      investigated. Comparison of the bFGF release profiles with the hydrogel erosion
      profiles indicates that bFGF delivery from this class of hydrogels is mainly an
      erosion-controlled process and the rates of bFGF release can be modulated via
      choice of HBP or via variations in the mechanical properties of the hydrogels.
      Manipulation of hydrogel physical properties and erosion profiles will provide
      novel materials for controlled growth factor delivery and other biomedical
      applications.

PMID- 16890322
TI  - L858R EGFR mutation status correlated with clinico-pathological features of
      Japanese lung cancer.
AB  - Somatic mutations of the epidermal growth factor receptor (EGFR) gene were found
      in about 25-40% of Japanese lung cancer patients. These mutations are associated
      with clinical and radiographic responses to EGFR tyrosine kinase inhibitors. Most
      common mutation are arginine for leucine substitution at amino acid 858 (L858R)
      and exon 19 deletions, especially deletion type 1 mutation. We investigated these
      EGFR mutation statuses in 575 surgically treated non-small cell lung cancer
      (NSCLC) cases. Three-hundred and sixty-two adenocarcinoma cases were included.
      The presence or absence of EGFR mutations of kinase domains was analyzed by
      genotyping analysis (TaqMan assay; n=386, and LightCycler assay; n=98) and
      sequences (n=91). EGFR mutations (CTG; CGG; L858R) were found from 63 of 575 lung
      cancer patients. We also detected the deletion 1a type mutations (2235-2249 del
      GGAATTAAGAGAAGC) from 39 patients and deletion 1b type mutations (2236-2250 del
      GAATTAAGAGAAGCA) from 15 patients in exon 19. These mutation statuses were
      significantly correlated with gender, smoking status (never smoker versus
      smoker), and pathological subtypes (adenocarcinoma versus non-adenocarcinoma).
      L858R mutation (p<0.0001), but not deletion 1 type mutation (p=0.0665), was
      correlated with differentiation status (well versus moderately or poorly) of lung
      cancers. L858R mutation ratio was significantly higher in non-smoker (p=0.0496)
      and adenocaicinoma (p=0.0136) when compared to deletion 1 type mutations. The
      EGFR mutation status, especially L858R mutation might be correlated with the
      clinico-pathological features related to good response to gefitinib, such as
      gender, smoking history, and pathological subtypes of Japanese lung cancers.

PMID- 16890324
TI  - Finger rings should be removed prior to scrubbing.

PMID- 16890323
TI  - Elevation of serum l-lactate dehydrogenase B correlated with the clinical stage
      of lung cancer.
AB  - To identify potential biomarkers related with lung cancer metastasis, conditional
      media (CM) proteins collected from a primary non-small cell lung cancer (NSCLC)
      cell line NCI-H226 and its brain metastatic subline H226Br were analyzed by one
      dimensional electrophoresis (1-D PAGE) and matrix-assisted laser desorption/time
      of flight mass spectrometry (MALDI-TOF-MS). Twelve biomarkers were identified, of
      which l-lactate dehydrogenase B (LDHB) chain was significantly up-regulated in
      the CM of H226Br cell and was further validated in 105 lung cancer, 93 non-lung
      cancer, 41 benign lung disease, as well as 65 healthy individuals sera using
      enzyme-linked immunosorbent assay (ELISA). It was found that the levels of LDHB
      were specifically elevated in NSCLC sera compared with other groups and were
      progressively increased with the clinical stage. At the cutoff point 0.260 (OD
      value) on the receiver operating characteristic (ROC) curve, LDHB could
      comparatively discriminate lung cancer from benign lung disease and healthy
      control groups with sensitivity 81%, specificity 70% and total accuracy 76%.
      These findings demonstrated that secretome could open up a possibility to find,
      identify, and characterize novel biomarkers related with invasion and metastasis.

PMID- 16890325
TI  - Effect of estrogen on neprilysin expression in uterus and kidney of Sprague
      Dawley normotensive and heterozygous (mRen2)27-transgenic hypertensive rats.
AB  - The present study was designed to determine whether estrogen modulates the
      angiotensin processing enzymes in membrane homogenates obtained from uterus and
      kidney cortex and medulla of Sprague-Dawley (SD) and heterozygous (mRen2)27
      transgenic hypertensive (Tg(+)) female rats treated with or without 17beta
      estradiol (E2). We evaluated estrogen's influence on neprilysin (NEP), an
      endopeptidase that forms angiotensin-(1-7) [Ang-(1-7)] and on aminopeptidase
      (AMP), which degrades Ang-(1-7). Renal tissue from normotensive and hypertensive
      male rats was also evaluated. E2 up-regulated NEP mRNA in the uterus of both SD
      and Tg(+) and this was associated with increased NEP activity in the uterus of SD
      (0.31+/-0.03 nmol/min/mg versus 0.18+/-0.04 nmol/min/mg of protein, p<0.05) and
      Tg(+) (0.26+/-0.04 nmol/min/mg versus 0.13+/-0.02 nmol/min/mg of protein, p<0.05)
      female). E2 had no significant effect on NEP activity in cortex and medulla of
      hypertensive and normotensive female. In female animals, cortical NEP activity is
      two-fold higher than medullary; in males there is a four-fold higher cortical NEP
      activity as compared to medulla. In male animals, medullary NEP was significantly
      lower than females with or without E2 treatment; no gender specific effect was
      found in cortex. E2 treatment also caused a two-fold increase in AMP activity in
      the uterus and 1.6-fold decrease in kidney cortex of SD and Tg(+) female
      (p<0.05). Our studies indicate that NEP may be a primary candidate for increased
      Ang-(1-7) processing in the uterus with estrogen treatment; kidney NEP, on the
      other hand, showed no modulation by estrogen, suggesting that down regulation of
      other processing enzymes, like AMP and ACE, may come into play in the kidney with
      estrogen replacement. In addition, these studies showed that there is tissue
      specific regulation of NEP with estrogen treatment that is strain independent.

PMID- 16890326
TI  - Caloric restriction suppresses apoptotic cell death in the mammalian cochlea and
      leads to prevention of presbycusis.
AB  - Presbycusis is characterized by an age-related progressive decline of auditory
      function, and arises mainly from the degeneration of hair cells or spiral
      ganglion (SG) cells in the cochlea. Here we show that caloric restriction
      suppresses apoptotic cell death in the mouse cochlea and prevents late onset of
      presbycusis. Calorie restricted (CR) mice, which maintained body weight at the
      same level as that of young control (YC) mice, retained normal hearing and showed
      no cochlear degeneration. CR mice also showed a significant reduction in the
      number of TUNEL-positive cells and cleaved caspase-3-positive cells relative to
      middle-age control (MC) mice. Microarray analysis revealed that CR down-regulated
      the expression of 24 apoptotic genes, including Bak and Bim. Taken together, our
      findings suggest that loss of critical cells through apoptosis is an important
      mechanism of presbycusis in mammals, and that CR can retard this process by
      suppressing apoptosis in the inner ear tissue.

PMID- 16890327
TI  - 3D-QSAR CoMFA study on indenopyrazole derivatives as cyclin dependent kinase 4
      (CDK4) and cyclin dependent kinase 2 (CDK2) inhibitors.
AB  - Cyclin dependent kinases (CDKs) have appeared as an important drug targets over
      the years with diverse therapeutic potentials. With the objective of designing
      new chemical entities with enhanced inhibitory potencies against CDK 2 (CDK2) and
      CDK 4 (CDK4), the 3D-QSAR CoMFA study carried out on indenopyrazole derivatives
      as inhibitors of these kinases is presented here. The developed model showed a
      strong correlative and predictive capability having a cross validated correlation
      co-efficient of 0.747 for CDK4 and 0.755 for CDK2 inhibitions. The conventional
      and predictive correlation co-efficients were, respectively, found to be 0.913
      and 0.760 for CDK4, 0.941 and 0.765 for CDK2. The models could be employed to
      design ligands with enhanced inhibitory potencies and/or to predict the potencies
      of analogues to guide synthesis.

PMID- 16890328
TI  - Race equality education: implications of an audit of student learning.
AB  - Racial harassment continues to be a feature of the United Kingdom (UK) National
      Health Service (NHS). It has serious consequences for those at the receiving end
      and impacts negatively on attempts by the NHS to retain and recruit a diverse
      workforce. The prevalence and persistence of racist views and behaviours amongst
      NHS staff raises questions concerning the preparation and education of
      practitioners. In 2004 the Faculty of Health and Social Care, University of the
      West of England, Bristol, piloted a training workshop to prepare students on a
      pre-qualifying adult nursing programme to prevent, recognise and effectively
      manage incidences of racial harassment in the workplace. Students found the
      training workshop useful to their learning. They felt more aware of racial
      harassment issues in the NHS and the specific actions they can take in the
      prevention and management of these. The findings support introduction of the
      training workshop as an integral component of the preparation of all students on
      the Faculty's pre-qualifying nursing programmes.

PMID- 16890329
TI  - Peptide selection for human immunodeficiency virus type 1 CTL-based vaccine
      evaluation.
AB  - Dozens of human immunodeficiency virus-type 1 (HIV-1) vaccine candidates
      specifically designed to elicit cytotoxic T-lymphocyte (CTL) responses have
      entered the pipeline of clinical trials. Evaluating the immunogenicity and
      potential efficacy of these HIV-1 vaccine candidates is challenging in the face
      of the extensive viral genetic diversity of circulating strains. Standardized
      peptide reagents to define the magnitude and potential breadth of the T-cell
      response, especially to circulating strains of HIV-1, are needed. For this
      purpose we developed a biometric approach based on T-cell recognition pattern for
      defining standardized reagents. Circulating strains in the Los Alamos database
      were evaluated and standardized algorithms to define all potential T-cell
      epitopes (PTEs) were generated. While many unique PTEs could be identified, a
      finite number based upon prevalence of circulating strains in the database, which
      we define as vaccine-important PTEs (VIPs), were used to select a common
      standardized panel of HIV-1 peptides for CTL-based vaccine evaluation. The
      usability of PTE peptide set was manifested by detection of Nef-specific CTL
      responses in HIV-1 subtype B infections.

PMID- 16890330
TI  - Factors underlying suboptimal childhood immunisation.
AB  - This review considers possible reasons behind parents' missed vaccination
      opportunities in the context of the latest immunisation coverage rates for
      England. Suboptimal uptake is not exclusive to measles, mumps and rubella (MMR).
      A substantial proportion of children also miss diphtheria, tetanus and polio
      vaccination. For MMR and diphtheria, tetanus and polio, uptake of primary plus
      booster immunisation is lower than for the primary course alone. Several reasons
      for suboptimal uptake are identified from the international literature. These
      provide insights into parental decision-making and potential barriers to
      immunisation that may need to be addressed in efforts to improve coverage rates.

PMID- 16890331
TI  - Distribution of elements in needles of Pinus massoniana (Lamb.) was uneven and
      affected by needle age.
AB  - Macronutrients (P, S, K, Na, Mg, Ca), heavy metals (Fe, Zn, Mn, Cu, Pb, Cr, Ni,
      Cd,) and Al concentrations as well as values of Ca/Al in the tip, middle and base
      sections, and sheaths of current year and previous year needles of Pinus
      massoniana from Xiqiao Mountain were analyzed and the distribution patterns of
      those elements were compared. The results indicated that many elements were
      unevenly distributed among the different components of needles. Possible
      deficiency of P, K, Ca, Mn and Al toxicity occurred in needles under air
      pollution. Heavy metals may threaten the health of Masson pine. Needle sheaths
      were good places to look for particulate pollutants, in this case including Fe,
      Cu, Zn, Pb, Cr, Cd and Al.

PMID- 16890332
TI  - Selective bioaccumulation of chlorinated pesticides and metabolites in Arctic
      seabirds.
AB  - Chlorinated pesticides and metabolites (CPs) were quantified in the seabird
      species: little auk (Alle alle), Brunnich's guillemot (Uria lomvia), black
      guillemot (Cepphus grylle) and black-legged kittiwake (Rissa tridactyla). The
      purpose was to evaluate avian accumulation of selected CPs based on their
      concentrations and relative patterns, their relation to dietary descriptors
      (stable isotopes of carbon and nitrogen), to enzymes involved in
      biotransformation, as well as CPs' accumulation potential relative to the
      recalcitrant polychlorinated biphenyl PCB-153. In all species, the CP pattern was
      dominated by p,p'-dichlorodiphenyltrichloroethane (DDE) and hexachlorbenzene
      (HCB). Except for HCB, concentrations were not related to trophic position. Most
      CPs were quantified in black guillemot, indicating a slower elimination compared
      to other seabird species. Brunnich's guillemot showed efficient elimination of
      chlordanes, whereas the opposite was found for little auk. Kittiwake showed
      higher accumulation of persistent CP and metabolites than auks, whereas
      accumulation of less recalcitrant CPs was low.

PMID- 16890333
TI  - Fluxes of N2O, CH4 and CO2 in a meadow ecosystem exposed to elevated ozone and
      carbon dioxide for three years.
AB  - Open-top chambers (OTCs) were used to evaluate the effects of moderately elevated
      O3 (40-50 ppb) and CO2 (+100 ppm) and their combination on N2O, CH4 and CO2
      fluxes from ground-planted meadow mesocosms. Bimonthly measurements in 2002-2004
      showed that the daily fluxes of N2O, CH4 and CO2 reacted mainly to elevated O3,
      while the fluxes of CO2 also responded to elevated CO2. However, the fluxes did
      not show any marked response when elevated O3 and CO2 were combined. N2O and CO2
      emissions were best explained by soil water content and air and soil
      temperatures, and they were not clearly associated with potential nitrification
      and denitrification. Our results suggest that the increasing O3 and/or CO2
      concentrations may affect the N2O, CH4 and CO2 fluxes from the soil, but longer
      study periods are needed to verify the actual consequences of climate change for
      greenhouse gas emissions.

PMID- 16890334
TI  - Enhanced desorption of phenanthrene from contaminated soil using anionic/nonionic
      mixed surfactant.
AB  - A new approach using an anionic/nonionic mixed surfactant, sodium dodecyl
      sulphate (SDS) with Triton X-100 (TX100), was utilized for the desorption of
      phenanthrene from an artificial contaminated natural soil in an aim to improve
      the efficiency of surfactant remediation technology. The experimental results
      showed that the presence of SDS not only reduced the sorption of TX100 onto the
      natural soil, but also enhanced the solubilization of TX100 for phenanthrene,
      both of which resulted in the distribution of phenanthrene in soil-water systems
      decreasing with increasing mole fraction of SDS in surfactant solutions. These
      results can be attributed to the formation of mixed micelles in surfactant
      solution and the corresponding decrease in the critical micelle concentration of
      TX100 in mixed solution. The batch desorption experiments showed that the
      desorption percentage of phenanthrene from the contaminated soil with mixed
      solution was greater than that with single TX100 solution and appeared to be
      positively related to the mole fraction of SDS in surfactant solution. Thus, the
      anionic/nonionic mixed surfactants are more effective for the desorption of
      phenanthrene from the contaminated soil than a single nonionic surfactant.

PMID- 16890335
TI  - Self-care as a response to diarrhoea in rural Bangladesh: empowered choice or
      enforced adoption?
AB  - The literature is growing on the subject of coping strategies. However, with the
      exception of some work on the promotion of oral rehydration therapy (ORT), very
      few studies have examined coping strategies as a response to the ongoing
      diarrhoeal disease burden. This is particularly relevant in the case of self
      care, previously documented as the most readily implemented treatment in the
      developing world and an increasingly common health behaviour in rural Bangladesh.
      This study analysed the socioeconomic factors that influence the adoption of self
      care and the role that varied asset availability plays in relation to households
      choosing, or being forced to implement, a coping strategy. Qualitative methods
      were used to collect data from three villages in Nilphamari District, North West
      Bangladesh, in 2004. The findings produced a detailed picture of asset
      availability and its influence on household use of self-care treatment practices.
      The strong role of aspects of social capital in building human capital was
      highlighted, as well as how these aspects of social capital can assist household
      welfare through self-care in times of diarrhoeal disease. In contrast, households
      exhibiting weakened social and human capital were more excluded from information
      on appropriate self-care treatments. Development agencies and health care
      policies might therefore strengthen levels of household resilience to diarrhoeal
      disease more cost-effectively by focusing on activities that facilitate self-care
      through support of social networks and education channels.

PMID- 16890336
TI  - Why Bangladeshi nurses avoid 'nursing': social and structural factors on hospital
      wards in Bangladesh.
AB  - In response to concerns that nurses spend less than 6% of their time on direct
      patient care, this study explored factors that influence nurses' behaviour in the
      provision of 'hands on' care in hospitals in Bangladesh. Through in-depth
      interviews with female nurses and patients and their co-workers in six hospitals,
      we identified conflicts between the inherited British model of nursing and
      Bangladeshi societal norms. This was most evident in the areas of night duty,
      contact with strangers, and involvement in 'dirty' work. The public was said to
      associate nursing activities with commercial sex work. As a consequence, their
      value on the 'bride market' decreases. To minimise the stigma associated with
      their profession, nurses in government hospitals distance themselves from
      patients, using nurse surrogates in the form of patients' relatives and hospital
      support workers to carry out their work. These adaptations are supported and
      sustained through unofficial activities developed over time within hospitals. In
      contrast nurses in NGO hospitals give more direct patient care themselves and do
      not rely on carers as much because of tight supervision and limited visitor
      hours. Initiatives undertaken to improve the quality of patient care, such as
      enlarging the nursing workforce or providing clinical instruction, which do not
      take into account the prevailing culture in hospitals and social conflicts faced
      by nurses, are unlikely to succeed. Fundamental decisions on how to care for the
      sick in Bangladesh are required. If the present nursing curriculum is followed,
      adequate supplies, supervision and accountability are prerequisites for its
      implementation.

PMID- 16890337
TI  - Access point analysis on the state of health care services in South African
      prisons: a qualitative exploration of correctional health care workers' and
      inmates' perspectives in Kwazulu-Natal and Mpumalanga.
AB  - This paper explores inmates and prison health care workers perceptions of the
      state of health care services in four correctional facilities in South Africa.
      Structural and organisational issues are explored in terms of how they impact the
      delivery and provision of health care to inmates within correctional facilities.
      Additionally, the study forms an access point analysis of prisons as a health
      care setting as part of the development and testing of a STI/HIV health education
      intervention for soon to be released inmates. Focus group discussions (6-8
      participants per group) were conducted with male inmates in four facilities in
      KwaZulu-Natal and Mpumalanga provinces. Individual face-to-face interviews were
      conducted with eight health personnel to get a view from both providers and end
      users of health care in correctional settings. Data were analysed thematically.
      We found strong evidence of prison being a strategic point to increase access to
      health services for offenders. Curative services within prisons were well
      established and running despite the presence of certain challenges varying across
      institutions. Prevention programmes emerged as an area that requires stronger
      emphasis to facilitate imparting skills and promoting safer practices for inmates
      upon release. Peer-led education programmes emerged as a key aspect of
      preparation for release and community reintegration amongst inmates.

PMID- 16890338
TI  - Normal patterns of deja experience in a healthy, blind male: challenging optical
      pathway delay theory.
AB  - We report the case of a 25-year-old healthy, blind male, MT, who experiences
      normal patterns of deja vu. The optical pathway delay theory of deja vu formation
      assumes that neuronal input from the optical pathways is necessary for the
      formation of the experience. Surprisingly, although the sensation of deja vu is
      known to be experienced by blind individuals, we believe this to be the first
      reported application of this knowledge to the understanding of the phenomenon.
      Visual input is not present in MT, yet the experiences he describes are
      consistent with reports in the literature of deja vu occurrence in sighted
      people. The fact that blind people can experience deja vu challenges the optical
      pathway delay theory, and alternative causes are briefly discussed.

PMID- 16890339
TI  - Reorganization of the composition of brain oscillations and their temporal
      characteristics in opioid dependent patients.
AB  - In the present study, we examined the composition of electroencephalographic
      (EEG) brain oscillations in broad frequency band (0.5-30 Hz) in 22 opioid
      dependent patients and 14 healthy subjects during resting condition (closed
      eyes). The exact compositions of brain oscillations and their temporal behavior
      were assessed by the probability-classification analysis of short-term EEG
      spectral patterns. It was demonstrated that EEG of patients with opioid
      dependence was characterized by (a) significant reorganization of brain
      oscillations with increase in the percentage of beta- and mostly fast-alpha
      rhythmic segments, (b) longer periods of temporal stabilization for alpha and
      beta brain oscillations and by shorter periods of temporal stabilization for
      theta and polyrhythmic activity when compared with control subjects, and (c)
      right-sided dominance (significantly larger relative presence of particular
      spectral patterns in EEG channels of the right hemisphere). These effects were
      widely distributed across the cortex with the maximum magnitude in the occipital,
      right parietal, temporal, and frontal areas. Taken together the present study
      suggested (a) an allostatic state with neuronal activation, and (b) high
      sensitivity of the right hemisphere to adverse opioid effects.

PMID- 16890340
TI  - Inhibition of tumor invasion and metastasis by aqueous extract of the radix of
      Platycodon grandiflorum.
AB  - Platycodon grandiflorum is a traditional oriental herbal medicine that is known
      for its immunostimulatory and anti-tumor effects. This study examined the anti
      metastatic activities of an aqueous extract from the root of P. grandiflorum
      (Changkil: CK) using in vitro and in vivo metastasis assays. CK inhibited the
      invasion of B16-F10 melanoma cells through a reconstituted basement membrane
      (Matrigel)-coated filter, and strongly inhibited the adhesion of B16-F10 melanoma
      cell to extracellular matrices such as Matrigel, fibronectin and laminin
      substrates. CK also inhibited an experimentally induced lung cancer and prolonged
      the survival time in vivo. In addition, CK augmented NK cell activity. These
      results show that CK can reduce the extent of a lung metastasis of B16-F10
      melanoma cells by inhibiting the adhesion of tumor cells to the basement membrane
      possibly and activating NK cells.

PMID- 16890341
TI  - Alignment/misalignment hypothesis for tRNA selection by the ribosome.
AB  - Transfer RNAs (tRNAs) are the adaptor molecules that allow the ribosome to decode
      genetic information during protein synthesis. During decoding, the ribosome must
      chose the tRNA whose anticodon corresponds to the codon inscribed in the
      messenger RNA to incorporate the correct amino acid into the growing polypeptide
      chain. Fidelity is improved dramatically by a GTP hydrolysis event. Information
      about the correctness of the anticodon must be sent from the decoding center to
      the elongation factor, EF-Tu, where the GTP hydrolysis takes place. A second
      discrimination event entails the accommodation of the aminoacyl-tRNA into its
      fully bound A/A state inside the ribosome. Here, we present a hypothesis for a
      specific mechanism of signal transduction through the tRNA, which operates during
      GTPase activation and accommodation. We propose that the rigidity of the tRNA
      plays an important role in the transmission of the decoding signal. While the
      tRNA must flex during binding and accommodation, its anisotropic stiffness
      enables precise positioning of the acceptor arm in the A/T state, the A/A state
      and the accommodation corridor. Correct alignment will result in optimal GTPase
      activation and accommodation rates. Incorrect tRNAs, however, whose anticodons
      are misaligned, will also have acceptor arms that are misaligned, resulting in
      sub-optimal GTPase activation and accommodation rates. In the case of GTPase
      activation, it is possible that the misalignment of the acceptor arm affects the
      rate directly, by altering the conformational change of the switch region of EF
      Tu, or indirectly, by changing the alignment of EF-Tu with respect to the sarcin
      ricin loop (SRL) of the large ribosomal subunit.

PMID- 16890342
TI  - Rate, accuracy and cost of ribosomes in bacterial cells.
AB  - Recent biochemical data on the rate of peptidyl-transfer and missense error
      levels associated with the E. coli ribosome in conjunction with direct
      measurements of diffusion constants for proteins in the E. coli cell have been
      used to discuss protein synthesis in the living E. coli cell in the perspective
      of a previously developed maximal fitness theory. With these improved
      experimental parameters, i.e. kcat approximately 50 s(-1) for protein elongation
      and kcat/KM approximately 4 microM(-1) s(-1) for cognate ternary complex binding
      to the ribosomal A site, theory predicts the experimentally observed variations
      in protein elongation rate, ribosome and ternary complex concentrations with
      varying quality of the growth medium. The theoretically predicted average
      missense error level is close the error levels estimated in vitro for special
      isoacceptor combinations, i.e. error levels about 1 per million. The future
      prospect of extensive integration of biochemistry, cell physiology and population
      genetics is discussed in the light of the maximal fitness theory and other,
      similar, theoretical approaches.

PMID- 16890343
TI  - Simple and complex spatiotemporal structures in a glycolytic allosteric enzyme
      model.
AB  - Pattern formation in glycolysis is studied with a classical reaction-diffusion
      allosteric enzyme model. It is found that, similar to recent experimental reports
      in the yeast extracts, a small magnitude local perturbation can induce transient
      target waves in a two dimensional oscillatory medium. An above threshold
      stimulation generates target waves which eventually evolve into spatiotemporal
      chaos upon collisions with the boundary or other wave activities. Detailed
      simulation studies show that the studied simple glycolytic reaction-diffusion
      model can support three types of spatiotemporal behaviors which are independent
      of the boundary conditions: (1) a spatially uniform stable steady state, (2)
      periodic global oscillations and (3) spatiotemporal chaos.

PMID- 16890344
TI  - The beta-turn scaffold of tripeptide containing an azaphenylalanine residue.
AB  - The conformational preferences of azaphenylalanine-containing peptide were
      investigated using a model compound, Ac-azaPhe-NHMe with ab initio method at the
      HF/3-21G and HF/6-31G(*) levels, and the seven minimum energy conformations with
      trans orientation of acetyl group and the 4 minimum energy conformations with cis
      orientation of acetyl group were found at the HF/6-31G(*) level if their mirror
      images were not considered. An average backbone dihedral angle of the 11 minimum
      energy conformations is phi=+/-91 degrees +/-24 degrees , psi =+/-18 degrees +/
      10 degrees (or +/-169 degrees +/-8 degrees ), corresponding to the i+2 position
      of beta-turn (delta(R)) or polyproline II (beta(P)) structure, respectively. The
      chi(1) angle in the aromatic side chain of azaPhe residue adopts preferentially
      between +/-60 degrees and +/-130 degrees, which reflect a steric hindrance
      between the N-terminal carbonyl group or the C-terminal amide group and the
      aromatic side chain with respect to the configuration of the acetyl group. These
      conformational preferences of Ac-azaPhe-NHMe predicted theoretically were
      compared with those of For-Phe-NHMe to characterize the structural role of azaPhe
      residue. Four tripeptides containing azaPhe residue, Boc-Xaa-azaPhe-Ala-OMe
      [Xaa=Gly(1), Ala(2), Phe(3), Asn(4)] were designed and synthesized to verify
      whether the backbone torsion angles of azaPhe reside are still the same as
      compared with theoretical conformations and how the preceding amino acids of
      azaPhe residue perturb the beta-turn skeleton in solution. The solution
      conformations of these tripeptide models containing azaPhe residue were
      determined in CDCl(3) and DMSO solvents using NMR and molecular modeling
      techniques. The characteristic NOE patterns, the temperature coefficients of
      amide protons and small solvent accessibility for the azapeptides 1-4 reveal to
      adopt the beta-turn structure. The structures of azapeptides containing azaPhe
      residue from a restrained molecular dynamics simulation indicated that average
      dihedral angles [(phi(1), psi(1)), (phi(2), psi(2))] of Xaa-azaPhe fragment in
      azapeptide, Boc-Xaa-azaPhe-Ala-OMe were [(-68 degrees, 135 degrees ), (116
      degrees, -1 degrees )], and this implies that the intercalation of an azaPhe
      residue in tripeptide induces the betaII-turn conformation, and the volume change
      of a preceding amino acid of azaPhe residue in tripeptides would not perturb
      seriously the backbone dihedral angle of beta-turn conformation. We believe such
      information could be critical in designing useful molecules containing azaPhe
      residue for drug discovery and peptide engineering.

PMID- 16890345
TI  - Evaluation of alternative landfill cover soils for attenuating hydrogen sulfide
      from construction and demolition (C&D) debris landfills.
AB  - Hydrogen sulfide (H(2)S) generated from C&D debris landfills has emerged as a
      major environmental concern due to odor problems and possible health impacts to
      landfill employees and surrounding residents. Research was performed to evaluate
      the performance of various cover materials as control measures for H(2)S
      emissions from C&D debris landfills. Twelve laboratory-scale simulated landfill
      columns containing gypsum drywall were operated under anaerobic conditions to
      promote H(2)S production. Five different cover materials were placed on top of
      the waste inside duplicate columns: (1) sandy soil, (2) sandy soil amended with
      lime, (3) clayey soil, (4) fine concrete (particle size less than 2.5 cm), and
      (5) coarse concrete (particle size greater than 2.5 cm). No cover was placed on
      two of the columns, which were used as controls. H(2)S concentrations measured
      from the middle of the waste layer ranged from 50,000 to 150,000 ppm. The
      different cover materials demonstrated varying H(2)S removal efficiencies. The
      sandy soil amended with lime and the fine concrete were the most effective for
      the control of H(2)S emissions. Both materials exhibited reduction efficiencies
      greater than 99%. The clayey and sandy soils exhibited lower reduction
      efficiencies, with average removal efficiencies of 65% and 30%, respectively. The
      coarse concrete was found to be the least efficient material as a result of its
      large particle size.

PMID- 16890346
TI  - Effect of contact order on the adsorption of inorganic arsenic species onto
      hematite in the presence of humic acid.
AB  - The speciation of aqueous and adsorbed As forms of arsenic (As) is a major
      environmental concern in the presence of humic acid (HA). The speciation during
      As adsorption process by the effect of contact order were evaluated in various
      equilibrated ternary systems consisting of As, HA and hematite. One ternary
      system was composed of the preequilibrated As(III)- or As(V)-HA complex, with the
      subsequent addition of hematite ((As-HA)-hematite system), and the other
      consisted of the preequilibrated HA-hematite, with the addition of As(III) or
      As(V) (As-(HA-hematite) system). The presence of HA led to a decrease in the As
      adsorption, opposite to cationic adsorption. The order of the amounts of As
      adsorption were found to follow as: As(V)-hematite>hematite-(As(V)-HA)>As(V)-(HA
      hematite)>As(III)-hematite>hematite-(As(III)-HA)>As(III)-(HA-hematite). Free
      As(V) and As-HA complex were preferentially adsorbed onto the hematite surface.
      The immobilization of As can come from adsorbed HA on mineral surfaces, and
      formation of As-HA complex, following their slow kinetics.

PMID- 16890347
TI  - Effects of exposure time and co-existing organic compounds on uptake of atrazine
      from nutrient solution by rice seedlings (Oryza sativa L.).
AB  - Root uptake of atrazine (ATR) by rice seedlings (Oryza sativa L.) from nutrient
      solution was investigated with exposure periods of 48, 96, and 240h. A similar
      ATR uptake was carried out with two co-existing organic compounds (o-chlorophenol
      (CP) and 2,4-dichlorophenol (DCP)) with 48h exposure. In contact with the
      seedlings, the ATR level in nutrient solution decreased sharply during the early
      exposure and then reached relatively steady levels after 48h. It was observed
      that the ATR levels within whole seedlings approached the estimated equilibrium
      partition limits in about 48h, according to the partition-limited model utilizing
      the measured plant water and organic matter contents and the ATR partition
      coefficients with whole seedlings. However, when roots and shoots were consisted
      separately, the detected ATR levels in roots were lower than estimated
      equilibrium limit while the levels in shoots exceeded the equilibrium limit. The
      data with roots suggested the occurrence of rapid ATR degradation in roots. The
      results with shoots are intrinsically consistent with the suggested complex
      formation of ATR with free metal ions in shoots. The ATR levels in roots and
      shoots varied to a moderate extent when the seedlings were exposed to different
      levels of ATR-CP-DCP mixtures. The variation results presumably from the
      interference of coexisting CP and DCP and the phytotoxicity of the mixed
      chemicals.

PMID- 16890348
TI  - Cadmium removal from aqueous solution by gene-modified Escherichia coli JM109.
AB  - The article extended the study on the bioaccumulation of cadmium by genetically
      engineered bacterium Escherichia coli (namely M4) simultaneously expressing a
      cadmium transport system and metallothionein (MT). The growth of M4 showed
      resistance to the presence of cadmium. Compared with Cd2+ uptake capacity by
      original host bacterial cells, The Cd2+ accumulation of M4 was enhanced more than
      one-fold. M4 could effectively bind Cd2+ over a range of pH from 4 to 8. The
      presence of Ni2+ and Mn2+ did not influence Cd2+ uptake remarkably, but Cu2+,
      Pb2+ and Zn2+ posed serious adverse effects. EDTA could drastically decrease Cd2+
      bioaccumulation by M4, whereas the effect of citrate was relatively slight.

PMID- 16890349
TI  - Sorption profile of Cd(II) ions onto beach sand from aqueous solutions.
AB  - Sorption of traces of Cd(II) ions onto beach sand is investigated as a function
      of nature and concentration of electrolyte (10(-4) to 10(-2)M nitric,
      hydrochloric and perchloric acids, pH 2-10 buffers and deionized water), shaking
      time 5-40min, shaking speed 50-200strokes/min, dosage of sand (50
      1000mg/15cm(3)), concentration of sorbate (1.04x10(-6) to 1.9x10(-4)M) and
      temperature (293-323K). Maximum sorption of Cd(II) ions (approximately 66%) is
      achieved from deionized water using 300mg/15cm(3) sand in 20min. The data are
      successfully tested by Langmuir, Freundlich and Dubinin-Redushkevich (D-R)
      sorption isotherms. The values for characteristic Langmuir constants Q=13.31+/
      0.20micromol/g and of b=(6.56+/-0.53)x10(3)dm(3)/mol, Freundlich constants
      A=2.23+/-1.16mmol/g and 1/n=0.70+/-0.05 of (D-R) constants beta=-0.005068+/
      0.000328kJ(2)/mol(2), X(m)=46.91+/-11.91micromol/g and energy E=9.92+/-0.32kJ/mol
      have been estimated. Kinetics of sorption has been studied by applying Morris
      Weber, Richenberg and Lagergren equations. The sorption follows first order rate
      equation resulting 0.182+/-0.004min(-1) The thermodynamic parameters
      DeltaH=32.09+/-2.92kJ/mol, DeltaS=111.0+/-9.5J/molK and DeltaG=-1.68+/-0.02kJ/mol
      are evaluated. The influence of common ions on the sorption of Cd(II) ions is
      also examined. Some common ions reduce the sorption while most of the ions have
      very little effect. It can be concluded that beach sand may be used as an
      alternative for the expensive synthetic sorbents.

PMID- 16890350
TI  - CGP 56999A, a GABA(B) receptor antagonist, enhances expression of brain-derived
      neurotrophic factor and attenuates dopamine depletion in the rat corpus striatum
      following a 6-hydroxydopamine lesion of the nigrostriatal pathway.
AB  - Rats were injected (i.p.) once daily with either 1 mg/kg CGP 56999A, a gamma
      aminobutyric acid(B) (GABA(B)) receptor antagonist, or an equivalent volume of
      saline beginning 7 days prior to, and continuing for 7 days following, a
      unilateral 6-hydroxydopamine lesion of the nigrostriatal dopamine (DA) pathway.
      At the end of the CGP 56999A treatment period the concentrations of DA and
      dihydroxyphenylacetic acid (DOPAC), as well as the expression of brain-derived
      neurotrophic factor (BDNF), were analyzed in corpus striatum ipsilateral and
      contralateral to the lesioning. No significant differences in these parameters
      were noted in the contralateral striatum between saline- and CGP 56999A-treated
      subjects. In contrast, as compared to animals receiving saline only, daily
      treatment with the GABA(B) receptor antagonist significantly attenuated the 6
      hydroxydopamine-induced decline in DA and increased the expression of BDNF in the
      ipsilateral striatum. The results indicate that CGP 56999A enhances BDNF gene
      expression in the rat corpus striatum and prevents the decline in DA content that
      is a characteristic sequela of 6-hydroxydopapmine lesions of the nigrostraital
      dopamine pathway. These findings suggest that GABA(B) receptor antagonists may be
      of value in the treatment of Parkinson's disease and other conditions that would
      benefit from an enhanced production of neurotrophic factors in brain.

PMID- 16890351
TI  - Rostral parvicellular reticular formation neurons projecting to rostral
      ventrolateral medulla receive cardiac inputs in anesthetized rats.
AB  - The rostral parvicellular reticular formation (rRFp) was explored
      electrophysiologically in urethane-chloralose anesthetized rats. Spontaneously
      active neurons that exhibited a pulse-related activity were recorded and tested
      for their projections to the rostral ventrolateral medulla (RVLM). About one
      third (10/29) of the rRFp neurons that exhibited a pulse-related activity were
      antidromically activated by RVLM stimulation with conduction velocities between
      0.2-4.4m/s and fell within the B and C fibre range. A majority (8/10) of these
      neurons had a low (<10spikes/s) mean firing rate, whereas a small proportion
      (2/10) had a high (>15spikes/s) mean firing rate. These findings suggest a direct
      pathway from the rRFp to the RVLM and suggest that neurons projecting to the RVLM
      receive cardiac inputs and can modulate RVLM neuronal activity.

PMID- 16890352
TI  - Divergence of ape and human monoamine oxidase A gene promoters: comparative
      analysis of polymorphisms, tandem repeat structures and transcriptional
      activities on reporter gene expression.
AB  - A variable number of tandem repeats (VNTR) polymorphism based on a 30-bp unit
      have been reported in the promoter region of the human monoamine oxidase A gene
      (MAOA). Human VNTRs have been shown to affect transcriptional activity, and some
      reports suggest that VNTR polymorphisms are associated with psychoneurological
      disorders. VNTR polymorphism has also been reported in the ape MAOA promoter but
      the transcriptional activities of the alleles remain to be determined. In the
      present study, we sequenced the 1.3-kb promoter region of ape MAOA and compared
      the transcriptional activities of ape MAOA promoter sequences with those of
      humans. All apes examined were polymorphic in the region corresponding to the
      human VNTR and two, four, three, and two alleles were found in chimpanzees,
      gorillas, orangutans, and gibbons, respectively. VNTR repeat structures in
      gorillas, orangutans, and gibbons were considerably different from those in
      humans and chimpanzees. In a human neuroblastoma cell line, most of the ape
      sequences that had a short repeat length (12bp or 18bp) exhibited higher promoter
      activity than a human 3-repeat sequence with a 30-bp repeat length. However, an
      intra-species difference dependent on the repeat number was not observed among
      the ape alleles examined.

PMID- 16890353
TI  - Implications of protease M/neurosin in myelination during experimental
      demyelination and remyelination.
AB  - Protease M/neurosin is a serine protease expressed by oligodendrocytes (OLGs) in
      the central nervous system (CNS). To investigate the role of protease M/neurosin
      during experimental demyelination and remyelination, mice were fed cuprizone (bis
      cyclohexanon oxaldihydrazone). Semi-quantitative RT-PCR analysis and
      immunohistochemistry revealed that the expressions of protease M/neurosin mRNA
      and protein were rapidly reduced in demyelination, whereas the expression of
      protease M/neurosin was increased in pi form of glutathione-S-transferases (GST
      pi)-positive OLGs during remyelination. Cultured primary OLGs displayed a strong
      correlation between protease M/neurosin and myelin basic protein (MBP). After
      tumor necrosis factor-alpha (TNF-alpha) and IFN-gamma stimulation, these proteins
      showed colocalization in the oligodendroglial process. The suppression of
      protease M/neurosin using RNAi reduced the level of MBP mRNA in cultured OLGs. In
      contrast, the reduced level of protease M/neurosin was not associated with
      oligodendroglial cell death or differentiation in cultured OLGs. This study
      identifies that protease M/neurosin in OLGs is closely associated with the
      expression of the MBP and the PLP gene. Our data emphasize that the maintenance
      of myelination is an important function of protease M/neurosin in OLGs,
      suggesting its relation to the oligodendroglial response to myelin disorders.

PMID- 16890354
TI  - An experimental study of shared sensitivity to physical pain and social
      rejection.
AB  - Recent evidence points to a possible overlap in the neural systems underlying the
      distressing experience that accompanies physical pain and social rejection
      (Eisenberger et al., 2003). The present study tested two hypotheses that stem
      from this suggested overlap, namely: (1) that baseline sensitivity to physical
      pain will predict sensitivity to social rejection and (2) that experiences that
      heighten social distress will heighten sensitivity to physical pain as well. In
      the current study, participants' baseline cutaneous heat pain unpleasantness
      thresholds were assessed prior to the completion of a task that manipulated
      feelings of social distress. During this task, participants played a virtual ball
      tossing game, allegedly with two other individuals, in which they were either
      continuously included (social inclusion condition) or they were left out of the
      game by either never being included or by being overtly excluded (social
      rejection conditions). At the end of the game, three pain stimuli were delivered
      and participants rated the unpleasantness of each. Results indicated that greater
      baseline sensitivity to pain (lower pain unpleasantness thresholds) was
      associated with greater self-reported social distress in response to the social
      rejection conditions. Additionally, for those in the social rejection conditions,
      greater reports of social distress were associated with greater reports of pain
      unpleasantness to the thermal stimuli delivered at the end of the game. These
      results provide additional support for the hypothesis that pain distress and
      social distress share neurocognitive substrates. Implications for clinical
      populations are discussed.

PMID- 16890355
TI  - The psychometric quality and clinical usefulness of three pain assessment tools
      for elderly people with dementia.
AB  - In view of the need for valid, reliable, and clinically useful scales to assess
      pain in elderly people with dementia, this study evaluated the psychometric
      properties of translated versions of the PAINAD, PACSLAC, and DOLOPLUS-2 scales.
      In an observational study design, two raters simultaneously assessed the nursing
      home residents (n=128) for pain during influenza vaccination and care situations.
      The PACSLAC was valued as the most useful scale by nurses. Cronbach's alpha was
      high (>.80) for the total scale at T2 and T3 and adequate for the 'Facial
      expression' and 'Social/personality/mood' subscales. IC scores for the
      'Activity/body movement' and 'Physiological indicators/eating/sleeping
      changes/vocal behaviors' subscales were low. It demonstrated good validity and
      reliability, although the scale should be further refined. This refinement should
      increase homogeneity. The PAINAD showed good psychometric qualities in terms of
      reliability, validity, and homogeneity (alpha ranged .69-.74 at T2 and T3)
      (except for the 'Breathing' item). The PAINAD scale had lower scores for clinical
      usefulness in this sample. The Dutch version of the DOLOPLUS-2 was considered
      more difficult to use but showed acceptable psychometric qualities in terms of
      the issues assessed, except for the 'psychosocial reactions' subscale. IC of the
      DOLOPLUS were adequate for the total scale (alpha ranged .74-.75) and almost all
      subscales (alpha ranged .58-.80). Findings of this study provide evidence of
      validity and reliability of the three pain assessment scales. Now that a pain
      scale is available, future studies also need to focus on its implementation in
      nursing practice.

PMID- 16890356
TI  - Emotional modulation of spinal nociception and pain: the impact of predictable
      noxious stimulation.
AB  - Recent evidence suggests that emotional picture-viewing is a reliable method of
      engaging descending modulation of spinal nociception. The present study attempted
      to replicate these findings and determine the effect of noxious stimulus
      predictability. Participants viewed pictures from the International Affective
      Picture System (IAPS), during which pain and nociceptive flexion reflexes (NFR)
      were elicited by electric shocks delivered to the sural nerve. For half of the
      participants (n=25) shocks were preceded by a cue (predictable), whereas the
      other half received no cue (unpredictable). Results suggested emotion was
      successfully induced by pictures, but the effect of picture-viewing on the NFR
      was moderated by the predictability of the shocks. When shock was unpredictable,
      spinal nociception (NFR) and pain ratings were modulated in parallel.
      Specifically, pain and NFR magnitudes were lower during pleasant emotions and
      higher during unpleasant emotions. However, when shocks were predictable, only
      pain was modulated in this way. NFRs from predictable shocks were not altered by
      pictures. Further, exploratory analyses found that pain ratings, but not NFRs,
      were lower during predictable shocks. These data suggest emotional picture
      viewing is a reliable method of engaging descending modulation of spinal
      nociception. However, descending modulation could not be detected in NFRs
      resulting from predictable noxious stimuli. Although preliminary, this study
      implies that separate mechanisms are responsible for emotional modulation of
      nociception at spinal vs. supraspinal levels, and that predictable noxious events
      may disengage modulation at the spinal level. The current paradigm could serve as
      a useful tool for studying descending modulation.

PMID- 16890357
TI  - Categories of placebo response in the absence of site-specific expectation of
      analgesia.
AB  - Experimental placebo analgesia is induced by building an expectation of reduced
      pain in a specific body part, usually using an inert cream in the guise of a
      local anaesthetic in conjunction with conditioning. We investigated non-site
      specific placebo analgesia by conditioning subjects to expect the anaesthetic
      cream on one arm, without specifying if they will definitely receive the cream,
      or to which arm it might be applied. Painful heat pulses (150 ms) from a CO2
      laser were delivered randomly to both arms. A treatment group (n=24) underwent
      three experimental blocks (pre-cream, conditioning after cream, and post
      conditioning). During the conditioning block, the intensity of the stimulus was
      reduced on one arm only. In the post-conditioning block it was returned to the
      painful level. We evaluated the change of intensity rating post-conditioning
      compared to the pre-cream block. In contrast to a control group (n=16), the
      treatment group reported a significant reduction in intensity ratings
      (F(1,38)=12.1; p=0.001). In the treatment group, we observed a range of placebo
      responses: unilateral responders (33.3%), subjects with a placebo response in the
      conditioned arm only; bilateral responders (33.3%), subjects reporting reduction
      in the intensity ratings in both arms, and non-responders, whose intensity
      ratings were not influenced by conditioning. We discuss these responses in terms
      of different levels of expected analgesia, facilitated by the absence of a site
      specific focus for the treatment. We suggest this allowed the individuals
      suggestibility to influence their assessment of the pain experience by combining
      different levels of expectation with the information from the actual pain
      stimulus.

PMID- 16890358
TI  - Reducing the missing wedge: High-resolution dual axis tomography of inorganic
      materials.
AB  - Electron tomography is a powerful technique that can probe the three-dimensional
      (3-D) structure of materials. Recently, this technique has been successfully
      applied to inorganic materials using Z-contrast imaging in a scanning
      transmission electron microscope to image nanomaterials in 3-D with a resolution
      of 1 nm in all three spatial dimensions. However, an artifact intrinsic to this
      technique limits the amount of information obtainable from any object, namely the
      missing wedge. One way to circumvent this problem is to acquire data from two
      perpendicular tilt axes, a technique called "dual axis tomography." This paper
      presents the first dual axis data at high resolution for inorganic materials, and
      by studying a CdTe tetrapod sample, demonstrates the increase in information
      obtained using this technique.

PMID- 16890359
TI  - Biting flies and Trypanosoma vivax infection in three highland districts
      bordering lake Tana, Ethiopia.
AB  - An epidemiological study was conducted to determine the prevalence of
      trypanosomosis in cattle, small ruminants and Equidae, and to identify biting
      flies; potential mechanical vectors of trypanosomes in the three districts of
      Bahir Dar Zuria, Dembia and Fogera, bordering lake Tana, Ethiopia. About 1509
      cattle, 798 small ruminants and 749 Equidae were bled for the prevalence study
      using the buffy-coat method and the measurement of the hematocrit value. Sixty
      six NGU and 20 monoconical traps were deployed for the fly survey. The results
      indicated the presence of trypanosomes in 6.1% (92/1509) of the cattle with a
      maximum during the late rainy season (9.6%) than the early dry season (3.6%) at
      Fogera district. Prevalence at the district level varied from 4% to 9.6%. Only
      one sheep (1/122) and one goat (1/676) were found positive for T. vivax-like
      trypanosomes and none of the Equidae was positive. All the trypanosomes
      encountered in cattle belong to the single species of T. vivax. The PCV was
      negatively associated with detection of T. vivax (21.6% in infected versus 25.4%
      in non-infected cattle). A total of 55,398 biting flies were caught of which
      49,353 (89.08%) belong to Stomoxys, 4715 (8.51%) to horse flies and 1330 (2.4%)
      to Chrysops species. There was no tsetse fly. Species identification has
      indicated the presence of Atylotus agrestis, Chrysops streptobalia, Stomoxys
      calcitrans, S. nigra, S. pulla, S. pallida, S. sitiens, S. taeniata, S. uruma,
      Haematopota lasiops and Hippobosca variegata. The overall apparent density was
      214.7flies/trap/day. Seasonal comparison showed higher fly catches in the late
      rainy season than the early dry season. This study indicated that T. vivax
      infections culminate in cattle at the same time as mechanical vectors such as
      Stomoxys sp. and Atylotus agrestis. Therefore, attention towards T. vivax
      infection in cattle is essential to control the impact of the disease on
      productivity. A further study on biting flies is recommended.

PMID- 16890360
TI  - Short time exposure to hypoxia promotes H9c2 cell growth.
AB  - The effects of short time (15 min) exposure to hypoxia on rat cardiomyocytes
      (H9c2) were examined. Exposure to hypoxia inhibited cell death via activation of
      MEK/extracellular signal-regulated kinase (ERK). Further, exposure to hypoxia
      promoted cell growth by down-regulation of p27 and phosphorylation of cyclin
      dependent kinase 2 (CDK2) and retinoblastoma protein (Rb).

PMID- 16890361
TI  - Metabolic effects of l-alanyl-glutamine in burned rats.
AB  - Burn injury elicits a sustained hypermetabolic state characterized by accelerated
      hepatic synthesis of amino acids and proteolysis leading to negative nitrogen
      balance. This paper was aimed at studying the effects l-alanyl-glutamine (Ala
      Gln) exogenous offer to rats submitted to thermal burn. Twenty-four anesthetized
      male Wistar rats were submitted to scald burn of dorsal skin (30% body surface).
      Eighteen and 42-h later rats were randomized to receive (by gavage) 2ml of water
      (G-1) or equal volume (0.5g/kg weight/day) of Ala-Gln solution (G-2). Tissue and
      blood samples were collected at the end of 24 and 48-h post-burn trauma (PBT).
      Blood concentrations of metabolites (glucose, pyruvate, lactate and ketone
      bodies) were similar in all groups. There were significant differences in tissue
      metabolites concentrations in Ala-Gln treated rats (G-2) compared to control (G
      1) following scald injury. The administration of Ala-Gln to burned rats induces a
      fall ATP (muscle, healthy skin), pyruvate and ketone bodies (liver)
      concentrations 24-h PBT. It also induces significant increase of lactate (burned
      skin) 24-h and glucose (liver) 28/48-h PBT. Rise of tissue lactate concentrations
      may be due to enhanced anaerobic glycolysis resulting from increased availability
      of glutamate, derived from glutamine, with possible activation of the malate
      aspartate shuttle.

PMID- 16890362
TI  - Tension suture technique for skin graft fixation. A novel alternative to tie-over
      dressing.

PMID- 16890363
TI  - Vanity burns: an unusual case of chemical burn caused by nail glue.

PMID- 16890364
TI  - N-methyl-D-aspartate receptor 1 changes in the piglet braintem after nicotine
      and/or intermittent hypercapnic-hypoxia.
AB  - Prone sleeping and cigarette smoke exposure are two major risk factors for the
      sudden infant death syndrome (SIDS). Utilizing piglet models of early postnatal
      nicotine and/or intermittent hypercapnic-hypoxia (IHH) exposure, we tested the
      hypothesis that these exposures, separately or combined, increase N-methyl-D
      aspartate (NMDA) receptor 1 (NR1) expression in the brainstem medulla. We also
      tested for gender-specific effects. Three piglet exposure groups were compared
      against 14 controls; 1, nicotine [n = 14], 2, IHH [n = 10], and 3, nicotine+IHH
      [n = 14], with equal gender proportions in each group. Non-radioactive in situ
      hybridization and immunohistochemistry were performed for NR1 mRNA and protein
      expression, respectively, and were quantified in seven nuclei of the brainstem
      medulla. NR1 mRNA was significantly increased in the gracile and inferior olivary
      nucleus (ION) after nicotine exposure, in five of seven nuclei after IHH
      exposure, and in three of seven nuclei after nicotine+IHH. The increased mRNA
      changes were accompanied by increased protein only in the ION after IHH and
      nicotine+IHH (P = 0.019, and P = 0.008 respectively). By gender, control females
      had greater NR1 mRNA than males in the dorsal motor nucleus of vagus (P = 0.05)
      and for protein in the ION (P = 0.02). This gender difference was maintained
      after nicotine exposure in the ION with additional gender differences observed
      including greater mRNA in the cuneate nucleus (P = 0.04) and nucleus of the
      spinal trigeminal tract (P = 0.03) of males compared with females. Overall, more
      changes occurred at the mRNA level than protein, and IHH exposure induced more
      changes than nicotine or nicotine+IHH exposures. Together, these findings suggest
      that hypercapnic-hypoxic exposures (modeling prone sleeping or sleep apnea) are
      more likely to induce NMDA receptor changes in the developing brainstem than
      nicotine exposure alone.

PMID- 16890365
TI  - Alpha2-adrenergic activation in the lateral parabrachial nucleus induces NaCl
      intake under conditions of systemic hyperosmolarity.
AB  - The inhibition of sodium intake by increased plasma osmolarity may depend on
      inhibitory mechanisms present in the lateral parabrachial nucleus. Activation of
      alpha(2)-adrenergic receptors in the lateral parabrachial nucleus is suggested to
      deactivate inhibitory mechanisms present in this area increasing fluid depletion
      induced 0.3 M NaCl intake. Considering the possibility that lateral parabrachial
      nucleus inhibitory mechanisms are activated and restrain sodium intake in animals
      with increased plasma osmolarity, in the present study we investigated the
      effects on water and 0.3 M NaCl intake produced by the activation of alpha(2)
      adrenergic receptors in the lateral parabrachial nucleus in rats with increased
      plasma osmolarity. Male Holtzman rats with stainless steel cannulas implanted
      bilaterally into the lateral parabrachial nucleus were used. One hour after
      intragastric 2 M NaCl load (2 ml), bilateral injections of moxonidine (alpha(2)
      adrenergic/imidazoline receptor agonist, 0.5 nmol/0.2 microl, n=10) into the
      lateral parabrachial nucleus induced a strong ingestion of 0.3 M NaCl intake
      (19.1+/-5.5 ml/2 h vs. vehicle: 1.8+/-0.6 ml/2 h), without changing water intake
      (15.8+/-3.0 ml/2 h vs. vehicle: 9.3+/-2.0 ml/2 h). However, moxonidine into the
      lateral parabrachial nucleus in satiated rats not treated with 2 M NaCl produced
      no change on 0.3 M NaCl intake. The pre-treatment with RX 821002 (alpha(2)
      adrenergic receptor antagonist, 20 nmol/0.2 microl) into the lateral parabrachial
      nucleus almost abolished the effects of moxonidine on 0.3 M NaCl intake (4.7+/
      3.4 ml/2 h). The present results suggest that alpha(2)-adrenergic receptor
      activation in the lateral parabrachial nucleus blocks inhibitory mechanisms,
      thereby allowing ingestion of hypertonic NaCl under conditions of extracellular
      hyperosmolarity. We suggest that during cell dehydration, circuits subserving
      sodium appetite are activated, but at the same time strongly inhibited through
      the lateral parabrachial nucleus.

PMID- 16890366
TI  - Spatial and temporal patterns of serotonin release in the rat's lumbar spinal
      cord following electrical stimulation of the nucleus raphe magnus.
AB  - The monoamine neurotransmitter serotonin is released from spinal terminals of
      nucleus raphe magnus (NRM) neurons and important in sensory and motor control,
      but its pattern of release has remained unclear. Serotonin was measured by the
      high-resolution method of fast cyclic voltammetry (2 Hz) with carbon-fiber
      microelectrodes in lumbar segments (L3-L6) of halothane-anesthetized rats during
      electrical stimulation of the NRM. Because sites of serotonin release are often
      histologically remote from membrane transporters and receptors, rapid emergence
      into aggregate extracellular space was expected. Increased monoamine oxidation
      currents were found in 94% of trials of 50-Hz, 20-s NRM stimulation across all
      laminae. The estimated peak serotonin concentration averaged 37.8 nM (maximum 287
      nM), and was greater in dorsal and ventral laminae (I-III and VIII-IX) than in
      intermediate laminae (IV-VI). When measured near NRM-evoked changes, basal
      monoamine levels (relative to dorsal white matter) were highest in intermediate
      laminae, while changes in norepinephrine level produced by locus ceruleus (LC)
      stimulation were lowest in laminae II/III and VII. The NRM-evoked monoamine peak
      was linearly proportional to stimulus frequency (10-100 Hz). The peak often
      occurred before the stimulus ended (mean 15.6 s at 50 Hz, range 4-35 s)
      regardless of frequency, suggesting that release per impulse was constant during
      the rise but fell later. The latency from stimulus onset to electrochemical
      signal detection (mean 4.2 s, range 1-23 s) was inversely correlated with peak
      amplitude and directly correlated with time-to-peak. Quantitative modeling
      suggested that shorter latencies mostly reflected the time below detection
      threshold (5-10 nM), so that extrasynaptic serotonin was significantly elevated
      well within 1 s. Longer latencies (>5 s), which were confined to intermediate
      laminae, appeared mainly to be due to diffusion from distant sources. In
      conclusion, except possibly in intermediate laminae, serotonergic volume
      transmission is a significant mode of spinal control by the NRM.

PMID- 16890367
TI  - The induction of surface beta-amyloid binding proteins and enhanced cytotoxicity
      in cultured PC-12 and IMR-32 cells by advanced glycation end products.
AB  - During aging the non-enzymatic glycation of proteins and other molecules
      increases significantly, leading to the accumulation of advanced glycation end
      products (AGEs). These AGEs enhance inflammatory and autoimmune reactions with
      resultant cytotoxicity. We noted in an earlier study that individuals with
      Alzheimer's disease exhibit enhanced expression of the receptor for advanced
      glycation end-products (RAGE) on the surface of their leukocytes. In order to
      better understand the relationship between AGEs and the cell surface binding of
      amyloid-beta protein (Abeta) 42 we studied the effect of two AGEs: glycated
      bovine serum albumin (BSA), and epsilon-carboxymethyllysine-BSA (CML), a
      glycoxidation product, on the binding of Abeta42 to rat PC-12 and IMR-32 cells.
      We measured the expression of three potential cell surface receptors binding
      Abeta42: RAGE, beta-amyloid precursor protein (beta-APP), and the alpha7 subtype
      of the nicotinic acetylcholine receptor (alpha7nAChR) by using specific antibody
      probes. Incubation of PC-12 or IMR-32 cells with bovine serum albumin-advanced
      glycation end-product (BSA-AGE) or with CML induced small but significant
      concentration-dependent increases in the expression of beta-APP, RAGE, and
      alpha7nAChRs as measured by flow cytometry or by ELISA. Incubation of the cells
      with 48 microM of either of the AGEs combined with varying concentrations (138
      1100 nM) of Abeta42 resulted in the enhanced binding of the Abeta42 to the cell
      surface as compared with cells not exposed to the AGE co-treatment. The
      combination of AGE and Abeta treatment also resulted in the heightened expression
      of all three potential Abeta binding sites as well as their gene precursors.
      Exposure of cells to the same regimen of AGE plus Abeta resulted in the
      production of reactive oxygen species and mitochondrial toxicity. These results
      are consistent with the ability of AGEs to enhance the cell surface expression of
      diverse Abeta42 binding sites, a factor that can lead to the enhanced binding of
      amyloid and subsequent cell death.

PMID- 16890368
TI  - Allosteric enhancement of metabotropic glutamate receptor 5 function promotes
      spatial memory.
AB  - Group I metabotropic glutamate receptors (mGluRs) have been implicated in
      learning and memory formation. Recent findings indicate an important function of
      the group I mGluR subtype 5. Here, we used the Y-maze spatial alternation task
      and examined whether enhancement of intrinsic mGluR5 activity immediately after
      learning, i.e. during a critical period for memory consolidation, would have any
      consequences on long-term memory retention in rats. Intracerebroventricular
      application of the allosteric mGluR5 potentiator DFB (3,3'-difluorobenzaldazine)
      resulted in a marked improvement in spatial alternation retention when it was
      tested 24 h after training. The promnesic effect increased with the difficulty of
      the task and was apparently due to a substantial enhancement of consolidation.
      The applied dose of DFB did not cause behavioral changes in the open field, and
      was devoid of structural side-effects as evaluated by immunohistochemical
      examination. Our results suggest an important function of post-training mGluR5
      activation in some types of hippocampus-dependent spatial learning.

PMID- 16890369
TI  - Pain sensitivity in mice lacking the Ca(v)2.1alpha1 subunit of P/Q-type Ca2+
      channels.
AB  - The role of voltage-gated Ca(2+) (Ca(V)) channels in pain mechanisms has been the
      object of intense investigation using pharmacological approaches and, more
      recently, using mutant mouse models lacking the Ca(V)alpha(l) pore-forming
      subunit of N-, R- and T-type channels. The role of P/Q-type channels in
      nociception and pain transmission has been investigated by pharmacological
      approaches but remains to be fully elucidated. To address this issue, we have
      analyzed pain-related behavioral responses of null mutant mice for the
      Ca(V)2.1alpha(1) subunit of P/Q-type channels. Homozygous null mutant
      Ca(V)2.1alpha(1)-/- mice developed dystonia at 10-12 days after birth and did not
      survive past weaning. Tested at ages where motor deficit was either absent or
      very mild, Ca(V)2.1alpha(1)-/- mice showed reduced tail withdrawal latencies in
      the tail-flick test and reduced abdominal writhes in the acetic acid writhing
      test. Adult heterozygous Ca(V)2.1alpha(1)+/- mice did not show motor deficits in
      the rotarod and activity cage tests and did not show alterations in pain
      responses in the tail-flick test and the acetic acid writhing test. Strikingly,
      they showed a reduced licking response during the second phase of formalin
      induced inflammatory pain and a reduced mechanical allodynia in the chronic
      constriction injury model of neuropathic pain. Our findings show that P/Q-type
      channels play an antinociceptive role in sensitivity to non-injurious noxious
      thermal stimuli and a pronociceptive role in inflammatory and neuropathic pain
      states, pointing to an important role of Ca(V)2.1 channels in central
      sensitization.

PMID- 16890370
TI  - Hypothermic preconditioning reduces Purkinje cell death possibly by preventing
      the over-expression of inducible nitric oxide synthase in rat cerebellar slices
      after an in vitro simulated ischemia.
AB  - We showed that hypothermic preconditioning (HPC) increased survival of Purkinje
      neurons in rat cerebellar slices after oxygen-glucose deprivation (OGD). HPC also
      reduced the OGD-increased expression of high mobility group I (Y) proteins, a
      transcription factor that can enhance inducible nitric oxide synthase (iNOS)
      expression. iNOS is a putatively damaging protein that contributes to ischemic
      brain injury. Heat shock proteins (HSPs) can be induced by various stimuli to
      protect cells. We hypothesize that HPC induces neuroprotection by reducing the
      expression of putatively damaging proteins such as iNOS and/or by increasing the
      expression of putatively protective proteins such as HSPs. Cerebellar slices were
      prepared from adult male Sprague-Dawley rats and incubated in circulating
      artificial cerebrospinal fluid. OGD was for 20 min at 37 degrees C and was
      followed by a 5-h recovery at 37 degrees C before slices were used for
      morphological, immunohistochemical and Western analyses. HPC was performed by
      incubating slices at 33 degrees C for 20 min at 1 h before the OGD. HPC and
      aminoguanidine, an iNOS inhibitor, prevented OGD-induced Purkinje cell
      death/injury. OGD increased the expression of iNOS and nitrosylated proteins.
      These increases were abolished by aminoguanidine and HPC. Interestingly, the
      expression of HSP70 was increased by OGD but not by HPC. Our results suggest that
      an increased iNOS expression contributes to the pathophysiology of OGD-induced
      Purkinje neuronal death in our model. Our results also suggest the involvement of
      inhibiting the expression of the putatively damaging iNOS proteins in the HPC
      induced neuroprotection. HSP70 may not contribute to the HPC-induced
      neuroprotection.

PMID- 16890371
TI  - Microtopography of the dual corticothalamic projections originating from domains
      along the frequency axis of the cat primary auditory cortex.
AB  - Spatial relationships between clusters of corticothalamic (CT) large terminals
      originating from cortical domains tuned to different frequencies were examined by
      pair-injecting two different anterograde tracers. Large-terminal CT projection
      originating from layer 5 was highly divergent with each injection site producing,
      on average, 15 local clusters distributing throughout non-lemniscal thalamic
      nuclei following a single anterograde tracer injection in the cat primary
      auditory cortex. Paired injections in higher- and lower-frequency cortical
      domains, resulting in labeling of two independent sets of terminal clusters,
      showed five recognizable patterns of spatial interaction between them. (1) In the
      ventral division of the medial geniculate complex (vMGC), sheet-like plexuses of
      small terminals of different origins were situated in parallel, with minimal
      overlap. (2) Extensive overlap of two low-density plexuses of differently labeled
      small terminals was observed in the medial division of the medial geniculate
      complex (MGC). (3) At the transition zones between the vMGC and the superficial
      dorsal nucleus of the MGC dorsal division, and between the vMGC and the
      ventrolateral nucleus, there were relatively broad clusters of a high density of
      large-terminal structures from the two cortical domains, which overlapped
      extensively. (4) At multiple loci in the nonlemniscal nuclei, pairing of two
      small clusters of differently labeled large terminals was observed. (5) Small
      unpaired clusters of large terminals were also found in the nonlemniscal nuclei.
      For large terminals, approximately 14%, 59%, and 27% clusters per injection
      demonstrated patterns 3, 4, and 5, respectively. The results provide evidence for
      the precise topographical organization for the large-terminal CT system at the
      microscopic level despite its highly divergent projection. This
      microtopographical projection from the tonotopic cortical field to non-tonotopic
      thalamic nuclei may raise the possibility of presence of a map that has not been
      defined in auditory non-lemniscal thalamic nuclei yet.

PMID- 16890372
TI  - Large discrepancies in cellular distribution of the tonicity-induced expression
      of osmoprotective genes and their regulatory transcription factor TonEBP in rat
      brain.
AB  - Osmoprotective genes are tonicity-activated genes involved in cellular
      osmoadaptation to hypertonicity and considered to be regulated by a specific
      transcription factor called tonicity-responsive enhancer-binding protein
      (TonEBP). In the brain we had previously established that TonEBP was expressed
      and tonicity-induced in neurons only. Here we have compared in various brain
      regions of rats subjected to systemic hypertonicity, the cellular expression of
      TonEBP through immunocytochemistry and the cellular expression of osmoprotective
      genes, namely aldose reductase (AR), sodium-dependent myo-inositol transporter
      (SMIT), betaine/GABA transporter (BGT1) and taurine transporter (TauT), by in
      situ hybridization using non-radioactive digoxigenin-labeled riboprobes. In
      neurons where TonEBP was strongly tonicity-induced, AR-mRNA labeling was strongly
      increased in some subsets (e.g. hippocampus pyramidal cells, cerebellar Purkinje
      cells and neurons of the hypothalamic magnocellular nuclei) but remained
      undetectable in some other subsets (e.g. neurons in cerebral cortex). Tonicity
      induced AR-mRNA labeling was observed only several hours after the tonicity
      induced expression of TonEBP. SMIT-mRNA labeling was tonicity-induced as densely
      and evenly distributed dots in neuron poor regions (e.g. cerebral cortex layer I
      and hippocampus stratum lacunosum-moleculare). The tonicity-induced expression of
      SMIT-mRNA may thus occur in non-neuronal cells, presumably astrocytes, where
      TonEBP is neither significantly expressed, nor tonicity-induced. In neurons
      showing a strong tonicity-induced expression of TonEBP, no SMIT-mRNA labeling was
      observed. BGT1-mRNA and TauT-mRNA labeling could not be detected, even after
      systemic hypertonicity. The present work reveals large discrepancies between the
      cellular distribution of the tonicity-induced expression of osmoprotective genes
      and that of their regulatory transactivator TonEBP. Depending on the cell subsets
      and the osmoprotective genes, TonEBP may appear insufficient or conversely
      unnecessary for the tonicity-induced activation of an osmoprotective gene.
      Altogether our results show that brain cells, even from the same class, activate
      distinct osmoprotective genes through distinct activation processes to adapt to
      hypertonicity.

PMID- 16890373
TI  - Posteromedial lateral suprasylvian motion area modulates direction but not
      orientation preference in area 17 of cats.
AB  - In visual cortices of cats there are two major, largely parallel, feedforward
      processing streams which conduct visual information from the primary visual
      cortices to the parietal and temporal visual cortices, processing motion and form
      information, respectively. In addition to the feedforward streams, there exist
      many feedback projections from higher-order visual cortices to lower-order visual
      cortices. Using the intrinsic signal optical imaging, this study has examined the
      influence of feedback signals originating from area posteromedial lateral
      suprasylvian (PMLS), the dominant motion-processing region of the parietal
      cortex, on responses of neurons, orientational maps, and directional maps in
      cats' area 17 (striate cortex). The inactivation of area PMLS by local
      application of GABA resulted in the reduction of the magnitude of responses of
      area 17 cells though area 17 of the cat is mainly involved in form information
      processing rather than motion. Furthermore, inactivation of area PMLS abolished
      the global layout of direction maps in area 17 but did not affect the basic
      structure of the orientation maps in area 17. Thus, it appears that higher-order
      cortical areas along one information processing stream may exert cross-stream
      modulatory effects on fundamental properties of neurons located in the lower
      order areas along distinct information processing streams.

PMID- 16890374
TI  - Age-related alterations of GABAergic input to CA1 pyramidal neurons and its
      control by nicotinic acetylcholine receptors in rat hippocampus.
AB  - The aim of this study was to determine whether age-associated alterations in the
      GABAergic input to pyramidal neurons in the hippocampus are due to a dysfunction
      of GABAergic interneurons, and/or a decrease in their cholinergic control via
      nicotinic receptors (nAChRs). Electrophysiological recordings were obtained from
      pyramidal cells in the CA1 area of hippocampal slices from young (3-4 months old)
      and aged (25-30 months old) Sprague-Dawley rats. Synaptic GABA(A) receptor
      mediated inhibitory postsynaptic currents and inhibitory postsynaptic potentials
      induced by stimulation of the stratum oriens were significantly smaller in aged
      rats. The frequency (but not amplitude) of spontaneous and miniature GABA
      inhibitory postsynaptic currents (IPSCs) was reduced in aged rats, suggesting a
      presynaptic alteration. Tetanic stimulation of cholinergic afferents to release
      endogenous acetylcholine, or an exogenous application of the nAChR agonist
      cytisine, increased the frequency of spontaneous IPSCs in young rats; however
      these effects were not evident in aged rats, indicating that the nicotinic
      control of GABA release is lowered during aging. None of these age-related
      alterations were reversed by a chronic treatment with donepezil, a cholinesterase
      inhibitor. Immunofluorescent labeling of GABA interneurons with somatostatin
      (SOM), parvalbumin (PV) or calbindin (CB), together with the vesicular
      acetylcholine transporter VAChT, revealed a selective loss of subpopulations of
      SOM and CB positive interneurons. This loss was associated with a general
      decrease in density of the cholinergic network in aged rats. Thus, the lower
      GABAergic inhibition observed in the aged rat hippocampus is due to a selective
      loss/dysfunction of subpopulations of GABAergic interneurons, associated with a
      widespread cholinergic deficit.

PMID- 16890375
TI  - Developmental vitamin D (DVD) deficiency in the rat alters adult behaviour
      independently of HPA function.
AB  - Developmental vitamin D deficiency (DVD) has been shown to alter the orderly
      pattern of brain development. Even though the period of vitamin D deficiency is
      restricted to gestation this is sufficient to induce behavioural abnormalities in
      the adult offspring consistent with those seen in many animal models of
      schizophrenia. Given that some of these behavioural alterations could also be an
      indirect result of either impaired maternal hypothalamic pituitary axis (HPA)
      function (which in turn could influence maternal care) or the result of a
      permanent alteration in HPA function in the adult offspring we have examined HPA
      status in both maternal animals and adult offspring. In this study we have
      established that HPA function is normal in the maternally vitamin D deficient
      rat. We replicate the behavioural phenotype of hyperlocomotion whilst
      establishing that HPA function is also unchanged in the adult male offspring. We
      conclude that the behavioural alterations induced by DVD deficiency are due to
      some adverse event in brain development rather than via an alteration in stress
      response.

PMID- 16890376
TI  - Effects of early olfactory deprivation on novelty-seeking behavior and primary
      and secondary lymphoid organs in young rats.
AB  - The aim of this study was to investigate the effects of an early olfactory
      deprivation on novelty-seeking behavior and lymphoid organs during post-natal
      development in rats. Therefore, we performed a bilateral nasal obstruction on 8
      day-old rats and we studied its effects at 21 days of age. Animals exposed to
      nasal obstruction presented an increased plasma corticosterone level, an adrenal
      hypertrophy more marked in females (+68% in females and +29% in males compared to
      sham group), a reduced growth of olfactory bulbs only in females (-43% compared
      to sham group) and an impaired novelty-seeking behavior, which seemed also more
      marked in females. Moreover, thymus specific weight and ConA-induced
      proliferative activity of thymocytes were diminished after induction of nasal
      obstruction in females but not in males. At last, spleen specific weight was not
      affected by nasal obstruction, although mitogen-induced proliferative activity of
      splenocytes was diminished in both sexes. These data showed that early olfactory
      deprivation by nasal obstruction was associated with some behavioral, endocrine
      and immunological alterations, which may have serious consequences for the health
      and the social status of the individuals.

PMID- 16890378
TI  - Aneuploidy directly contribute to carcinogenesis by disrupting the asymmetric
      division of adult stem cells.

PMID- 16890377
TI  - Brain-derived neurotrophic factor Val66Met polymorphism and dexamethasone/CRH
      test results in depressed patients.
AB  - Data suggest that both neurotrophic and hypothalamic-pituitary-adrenocortical
      (HPA) systems are involved in the pathophysiology of depression. The aim of the
      present study was to investigate whether the non-conservative brain-derived
      neurotrophic factor (BDNF) Val66Met polymorphism has an impact on HPA axis
      activity in depressed patients. At admission, the dexamethasone/CRH (DEX/CRH)
      test was performed in 187 drug-free in-patients suffering from major depression
      or depressed state of bipolar disorder (DSM-IV criteria). Moreover, genotyping of
      BDNF Val66Met polymorphism was carried out using the fluorescence resonance
      energy transfer method (FRET). Homozygous carriers of the Met/Met genotype showed
      a significantly higher HPA axis activity during the DEX/CRH test than patients
      carrying the Val/Val or Val/Met genotype (ACTH, cortisol). Our results further
      contribute to the hypothesized association between HPA axis dysregulation and
      reduced neuroplasticity in depression and are consistent with the assumption that
      BDNF is a stress-responsive intercellular messenger modifying HPA axis activity.

PMID- 16890379
TI  - Role of bacterial superinfections in the pathogenesis of postzosteric neuralgia.
AB  - Varicella-zoster virus (VZV) is an alpha-herpes virus that causes varicella
      (chickenpox), establishes latency in dorsal root ganglia and may reactivate to
      cause herpes zoster (shingles). Postherpetic neuralgia is the most common
      debilitating complication of herpes zoster. It is currently supposed that
      scarring of the dorsal root ganglia and atrophy of the dorsal horn as a result of
      intense inflammation may play a central role in the pathogenesis of this
      condition. The exact pathogenesis of the inflammatory reaction leading to
      persistent ganglion damage is still poorly understood. However, immune
      suppression is a recognized risk factor for the development of postzosteric
      neuralgia in zoster patients (increased risk, e.g., in aged patients over 80
      years or diabetes mellitus patients). There is some evidence that remote
      streptococcal and staphylococcal infections may induce immunologic disease
      mechanisms consequently affecting the central nervous system. Since streptococcal
      and/or staphylococcal superinfection of skin lesions is common in herpes zoster,
      we present a hypothesis of immunopathogenesis of postzosteric neuralgia, i.e., as
      the result of augmentation of local ganglion inflammation due to bacteria-driven
      clonal expansion of VZV-specific T-cell subsets in the affected skin. Based on
      the aforementioned hypothesis it is interesting: (1) to study the impact of
      concomitant systemic antibiotic treatment to the standard antiviral regimen on
      the rate and severity of both bacterial superinfection of zoster skin lesions and
      postzosteric neuralgia and (2) to quantify the VZV-specific T-cell response as a
      function of the degree of bacterial superinfection of zoster skin lesions.
      Challenging of the present hypothesis should provide an effective means of
      preventing postherpetic neuralgia by preventing and consequently treating the
      bacterial superinfection of zoster skin lesions.

PMID- 16890382
TI  - Transcendental meditation may prevent partial epilepsy.

PMID- 16890381
TI  - Are HER1/EGFR interactions with ligand free HER2 related to the effects of HER1
      targeted drugs?
AB  - This paper is aimed to describe consequences of possible dimerization modes
      between ligand binding HER1 and ligand free HER2 receptors on cellular membrane.
      Cells without HER2/neu need high exposure to HER1 ligands for growth stimulation
      since formation of HER1-ligand:HER1-ligand homodimers depends on the number of
      both HER1 and ligand molecules and an "all or none" threshold under which cell
      growth is not stimulated can be expected. Cells with HER2/neu molecules on their
      surface can react to moderate or even low HER1 ligand exposure through formation
      of HER2:HER1-ligand dimers, making them more sensitive to growth stimulation by
      EGF or other ligands without the "all or none" threshold in cell growth
      stimulation. Formation of some HER2:HER2 homodimers can provide the basal cell
      growth stimulation despite available ligands to HER1. In tumors, high expression
      of HER2 can lead to many HER2:HER2 homodimers and increased cell growth that
      contributes to a poor prognosis. Here presented concept is that some 75 millions
      of years ago, introduction of HER2/neu with increased sensitivity to low EGFR
      ligand exposure, might be the cause of increased variability of HER1 expression
      on normal cells and of the basal EGF secretion from the uninjured tissue.
      Spontaneous formation of HER2:HER2 homodimers in cells with HER2/neu expression
      might have substituted the low ligand exposure from uninjured tissue and thus
      slowly reduce importance of basal secretions of EGFR ligands. Reported
      variability in HER1 tumor expression and response to HER1-targeted agents, a wide
      range of EGF concentration in healthy women breasts fluid and the skin rash/tumor
      response relation to HER1-targeted drugs are discussed as possible examples of
      individual differences in tissue dependency on HER1 interactions with ligands in
      normal and cancer tissue.

PMID- 16890380
TI  - Sporadic amyotrophic lateral sclerosis as an infectious disease: a possible role
      of cyanobacteria?
AB  - The available epidemiological data for amyotrophic lateral sclerosis (ALS)
      support an infectious etiology and lead us to propose a new hypothesis. We
      examined older epidemiological data concerning categories of the population with
      increased incidence (aged people, people living in rural areas, farmers,
      breeders), more recent epidemiological reports regarding Italian soccer players,
      AIDS patients, people living in highly polluted areas, and reports of cases of
      conjugal and pregnancy-associated ALS. The toxic and infectious hypotheses lead
      us to suggest a role for cyanobacteria in the production of endogenous beta-N
      methylamino-L-alanine. Infection from a cyanobacterium, or another ubiquitous
      bacterium having similar characteristics, may be the missing clue to the etiology
      of ALS. We speculate that ubiquitous bacteria secreting toxic amino acids and
      "colonizing" tissues and organs in the human body might be the common element
      linking motor neuron diseases in Guam to sporadic ALS in the rest of the world.

PMID- 16890383
TI  - Heparanase promotes angiogenesis through Cox-2 and HIF1alpha.
AB  - Heparanase has been given attention for its role in the invasion and metastasis
      of various cancers for years. We have also investigated and reported the role of
      heparanase in several human cancers, including gastric, esophageal and colon
      carcinomas. Other than the critical role of heparanase in tumor invasion and
      metastasis, it is also believed that heparanase is involved in angiogenesis,
      another feature of tumor progression which is complicatedly mediated by many
      molecules, including cyclooxygenese-2 (Cox-2). Thus, our recent study elucidated
      a possible relationship of heparanase with Cox-2 upon tumor angiogenesis. Based
      upon our study, three major transcription factor binding sites containing NF
      kappaB, NF-IL-6 and CRE sites seemed to have a compensative and cooperative role
      in heparanase-induced Cox-2 upregulation. On the other hand, tumor hypoxia often
      occurs in most tumors and Cox-2-induced HIF1alpha overexpression has recently
      been shown in various cancers. Here we believe that heparanase may also be
      involved in tumor hypoxia through the induction of HIFalpha either directly or
      indirectly through the Cox-2 pathway. This hypothesis indicates a possible novel
      function of heparanase and its link to HIF1alpha and Cox-2, and therefore this
      function would give us a clue about potential new strategies for cancer therapy.

PMID- 16890384
TI  - The P11, tPA/plasminogen system and brain-derived neurotrophic factor:
      Implications for the pathogenesis of major depression and the therapeutic
      mechanism of antidepressants.
AB  - Major depressive disorder (MDD) is a common disabling psychiatric illness with an
      unknown etiology. Evidence from animal and human studies suggests that a
      disturbance in serotonergic (5-HT) activity and/or brain-derived neurotrophic
      factor (BDNF) signaling may be implicated in the pathogenesis of MDD. Recently, a
      protein, p11, has been found to increase the number of 5-HT(1B) receptors on the
      surface of cells and enhance 5-HT(1B) receptor function. Furthermore, mice over
      expressing p11 acted as if they were undergoing treatment with antidepressants
      and p11 knockout mice exhibit a depression-like phenotype and reduced behavioural
      reactions to an antidepressant. As tissue-type plasminogen activator
      (tPA)/plasminogen proteolytic cascade is implicated in the cleavage of proBDNF to
      BDNF, and p11, a component of the Annexin II, which can greatly enhance the
      activation of plasmin by tPA, it is proposed that p11 may act through the
      tPA/plasminogen/BDNF pathway to achieve its antidepressant effect. Attempts to
      confirm this hypothesis may lead to new directions in the study of the
      pathogenesis of MDD and the development of a novel intervention for this
      disorder. In addition, BDNF is also implicated in several psychiatric diseases
      such as schizophrenia, bipolar disorder, attention-deficit hyperactivity disorder
      and Alzheimer's disease; whether p11 and other components related to the
      tPA/plasminogen pathway may be related to the pathogenesis of these diseases
      needs further exploration.

PMID- 16890385
TI  - Immunoglobulin is a highly diverse self-molecule that improves cellular diversity
      and function during immune reconstitution.
AB  - Paradoxically, human B cell immune deficiencies are associated with increased
      susceptibility to viral and fungi infections, which are T cell immunity related
      infections. Also, some viral infections occurring in immune depressed patients
      such as cytomegalovirus infections are recommended to be treated with intravenous
      immunoglobulin (IVIg) in combination with antiviral therapy. This fact has no
      clear biological explanation but it has been shown to be successful. Recently, B
      cells and immunoglobulin were identified as essential elements driving T cell
      receptor (TCR) diversity generation. Idiotype peptides of B cell immunoglobulin
      may be the driving force for the antigen presenting function of B cells and other
      antigen presenting cells to influence the T cell repertoire. This seems to be
      another relevance of Jerne's idiotypic network and another function of
      immunoglobulin. Since T cells function depends on the diversity of the TCR
      repertoire, means to increase the diversity of the T cell repertoire may improve
      T cell function in situations characterized by a contracted TCR repertoire, such
      as AIDS, primary immunodeficiency, cancer, autoimmunity and following
      chemotherapy and hematopoietic precursors transplantation. The clinical
      hypothesis here put forward is that B cells and/or immunoglobulin may be used
      therapeutically aiming to increase and potentially to restore T cell repertoire
      diversity improving T cell function in situations implicating a contracted T cell
      repertoire. The fact that immunoglobulin influence the composition of T cell
      repertoire by increasing its diversity allows a much wider application of this
      molecule in the clinical practice. Here is presented a novel reasoning for the
      use of IVIg in humans, which should be explored. All the situations where immune
      reconstitution occurs are potentially a target for this therapeutically
      mechanism, aiming to fast and improve the diversity of the reconstituted immune
      repertoires. This new role of Ig molecule, an old and widely therapeutically used
      molecule, may help to explain several effects that IVIg have in the T cell
      compartment, such as modulation of the activation and function of effectors T
      cells. The idea that immunoglobulin is essential in the generation and
      maintenance of a diverse compartment of T cells, affecting T cell function via
      that mechanism suggests a promising approach to medical conditions involving
      immune reconstitution. Furthermore, it represents a new paradigm of understanding
      the immune system as a complex, interdependent web of cells/cell products that
      inter-affect each other generation, function and survival.

PMID- 16890386
TI  - Antibacterial activity of Cuscuta reflexa stem and Corchorus olitorius seed.
AB  - The methanol extracts of Cuscuta reflexa stem and Corchorus olitorius seed showed
      a broad spectrum of antibacterial activity.

PMID- 16890387
TI  - Repellent activity of five essential oils against Culex pipiens.
AB  - Essential oils extracted from the seeds of anise (Pimpinella anisum), dried
      fruits of eucalyptus (Eucalyptus camaldulensis), dried foliage of mint (Mentha
      piperita) and basil (Ocimum basilicum) and fresh foliage of laurel (Laurus
      nobilis) were tested for their repellency against the adult females of Culex
      pipiens. All essential oils showed repellency in varying degrees, eucalyptus,
      basil and anise being the most active.

PMID- 16890389
TI  - Nitric oxide-dependent vasodilatation by ethanolic extract of Hancornia speciosa
      via phosphatidyl-inositol 3-kinase.
AB  - The vasodilator effect of the ethanolic extract of leaves from Hancornia speciosa
      Gomes (HSE) was studied in rat aortic rings. HSE produced a concentration
      dependent vasodilatation (pIC(50)=5.6+/-0.1), which was completely abolished in
      endothelium-denuded vessels. The endothelium-dependent vasodilatation induced by
      HSE was abolished by l-NAME (100 microM), a nitric oxide (NO) synthase inhibitor,
      but not atropine (1 microM; pIC(50)=5.6+/-0.2), a muscarinic receptor antagonist,
      nor indomethacin (10 microM; pIC(50)=5.4+/-0.2), a cyclooxygenase inhibitor. The
      concentration-response curve of HSE was significantly shifted to the left by
      superoxide dismutase (SOD; 300U/mL). In addition, while SOD displaced the 3
      morpholino-sidnonimine (SIN-1; P<0.05) concentration-effect curve to the left,
      HSE (50 microg/mL) had no effect. Finally, wortmannin (0.3 microM), an inhibitor
      of phosphatidyl-inositol 3-kinase (PI3K), dramatically reduced the vasodilator
      effect of HSE. Together, these findings lead us to conclude that HSE induces a NO
      and endothelium-dependent vasodilatation in rat aortic preparations, likely by a
      mechanism dependent on the activation of PI3K.

PMID- 16890388
TI  - Panax ginseng induces human Type I collagen synthesis through activation of Smad
      signaling.
AB  - Skin aging appears to be principally related to a decrease in levels of Type I
      collagen, the primary component of the dermal layer of skin. It is important to
      introduce an efficient agent for effective management of skin aging; this agent
      should have the fewest possible side effects and the greatest wrinkle-reducing
      effect. In the course of screening collagen production-promoting agents, we
      obtained Panax ginseng C.A. Meyer. This study was designed to investigate the
      possible collagen production-promoting activities of Panax ginseng C.A. Meyer
      root extract (PGRE) in human dermal fibroblast cells. As a first step to this
      end, human COL1A2 promoter luciferase assay was performed in human dermal
      fibroblast cells. In this assay, PGRE activated human COL1A2 promoter activity in
      a concentration-dependent manner. Human Type I procollagen synthesis was also
      induced by PGRE. These results suggest that PGRE promotes collagen production in
      human dermal fibroblast cells. Additionally, we have attempted to characterize
      the mechanism of action of PGRE in Type I procollagen synthesis. PGRE was found
      to induce the phosphorylation of Smad2, an important transcription factor in the
      production of Type I procollagen. When applied topically in a human skin primary
      irritation test, PGRE did not induce any adverse reactions. Therefore, based on
      these results, we suggest the possibility that PGRE may be considered as an
      attractive, wrinkle-reducing candidate for topical application.

PMID- 16890390
TI  - The use of serial measurement of plasma cholinesterase in the management of acute
      poisoning with organophosphates and carbamates.
AB  - OBJECTIVE: To evaluate the benefits of using serial measurements of plasma
      cholinesterase (butyrylcholinesterase, BuChE) activity in the management of
      cholinesterase inhibitor insecticidal poisoning. METHOD: After establishing and
      validating BuChE activity test, and making it available for clinical service in
      the toxicology laboratory at Jordan University Hospital. Serial measurements of
      BuChE were performed on samples taken from 10 symptomatic patients presented with
      the manifestations of poisoning due to acetylcholinesterase inhibitor
      insecticides during the year 2001. The number of serial repeats of BuChE activity
      tests ranged from 2 to 4 and from 8 to 11 for patients with carbamates and
      organophosphates (OPs) poisoning, respectively. The results of serial measurement
      of BuChE obtained from each patient's samples were used to draw a curve; three
      different types of curves were obtained from all patients samples. RESULT: The
      obtained curves were found to follow our three proposed curves, which support our
      point view regarding the importance of the proposed curves in the differential
      diagnosis and treatment of cholinesterase inhibitor pesticides poisoning.
      CONCLUSION: This study pointed out the importance of utilizing serial
      measurements of BuChE activity in the diagnosis and the management of
      organophosphates and carbamates poisoning. The BuChE activity results were used
      to support diagnostic and prognostic criteria that guided patient management and
      follow up. Applying those curves to large number of patients' samples will
      enhance its credibility. The study also demonstrated the importance of direct
      contract between toxicologist and physician in treatment of the pesticides
      poisoned patients.

PMID- 16890391
TI  - Multimodal biometrics for identity documents (MBioID).
AB  - The MBioID initiative has been set up to address the following germane question:
      What and how biometric technologies could be deployed in identity documents in
      the foreseeable future? This research effort proposes to look at current and
      future practices and systems of establishing and using biometric identity
      documents (IDs) and evaluate their effectiveness in large-scale developments. The
      first objective of the MBioID project is to present a review document
      establishing the current state-of-the-art related to the use of multimodal
      biometrics in an IDs application. This research report gives the main
      definitions, properties and the framework of use related to biometrics, an
      overview of the main standards developed in the biometric industry and
      standardisation organisations to ensure interoperability, as well as some of the
      legal framework and the issues associated to biometrics such as privacy and
      personal data protection. The state-of-the-art in terms of technological
      development is also summarised for a range of single biometric modalities (2D and
      3D face, fingerprint, iris, on-line signature and speech), chosen according to
      ICAO recommendations and availabilities, and for various multimodal approaches.
      This paper gives a summary of the main elements of that report. The second
      objective of the MBioID project is to propose relevant acquisition and evaluation
      protocols for a large-scale deployment of biometric IDs. Combined with the
      protocols, a multimodal database will be acquired in a realistic way, in order to
      be as close as possible to a real biometric IDs deployment. In this paper, the
      issues and solutions related to the acquisition setup are briefly presented.

PMID- 16890392
TI  - [Cerebral hydatid cysts in children: 4 cases].
AB  - The cerebral localization of the hydatid disease is rare, under 2%, and it
      primarily affects children. We report 4 cases of children presenting with a
      cerebral hydatid cyst (2 boys and 2 girls, mean age 9 years). Clinical symptoms
      were very progressive, the disease was frequently diagnosed several months (1-12
      months) after onset of symptoms most often headaches and vomiting. One patient
      presented with a right tonic-clonic seizure 3 days before hospitalization. The
      diagnostic was confirmed in all cases by Cerebral CT scan. All the patients were
      screened for other localizations. One patient also presented with pulmonary and
      hepatic hydatid cysts. Hydatid blood tests were positive in only one case. The
      treatment was surgical for all the patients (using hydropulsion) without
      complications in 2 cases. One child presented with meningitis, and the other
      child with signs of secondary ICHT related to residual mass which required its
      puncture.

PMID- 16890394
TI  - Development of gas chromatography-mass spectrometry with microwave distillation
      and simultaneous solid-phase microextraction for rapid determination of volatile
      constituents in ginger.
AB  - In this study, gas chromatography-mass spectrometry (GC-MS) following microwave
      distillation and solid-phase microextraction (MD-SPME) was developed for the
      analysis of essential oil compounds in fresh ginger. In the proposed method, the
      isolation, extraction and concentration of volatile components in ginger were
      carried out in one single step, using the MD-SPME technique, and the analytes on
      the SPME fiber were analyzed by GC-MS. Some parameters, including SPME fiber
      coating, microwave power and irradiation time, were optimized. The optimal
      experiment parameters obtained were: 65 microm PDMS/DVB SPME fiber, a microwave
      power of 400 W and an irradiation time of 2 min. To demonstrate its feasibility,
      MD-SPME was compared with conventional SPME for the extraction of essential oil
      compounds in fresh ginger. Using MD-SPME followed by GC-MS, 54 compounds were
      separated and identified in ginger, which mainly included geranial (5.25%),
      zingiberene (15.48%), beta-sesquiphellandrene (5.54%) and beta-phellandrene
      (22.84%), whereas only 39 compounds were separated and identified by conventional
      SPME followed by GC-MS. The relative standard deviation (R.S.D.) values of less
      than 10% show that the proposed method has good repeatability. The result show
      that MD-SPME, followed by GC-MS, is a simple, rapid, solvent-free method for the
      determination of volatile compounds in ginger.

PMID- 16890395
TI  - [From end-of-life management to euthanasia].

PMID- 16890393
TI  - Mammographically detected breast arterial calcifications: indicators for
      arteriosclerotic diseases?
AB  - PURPOSE: To determine the prevalence of breast arterial calcifications (BAC)
      detected on mammography and search for conditions that may influence their
      existence. MATERIALS AND METHODS: The mammograms of 6156 consecutive patients
      were reevaluated for the presence of BAC. Four hundred eighty-five women having
      BAC were enrolled in the patient group. Additionally, randomly selected 500
      women, without BAC constituted the control group. Hospital records of the
      participants were reviewed for parity, menopausal status, oral contraceptive
      agent (OCA) usage, hormone replacement therapy (HRT) usage, presence of diabetes,
      hypertension, hyperlipidemia, albuminuria and history of myocardial infarction
      (MI). RESULTS: Prevalence of BAC was 7.9% on mammograms. Ninety-four women were
      aged between 40 and 49 years, 165 were aged between 50 and 59 years and 226 were
      over 60 years among BAC positive 485 women. A significant relationship was found
      for the frequency of BAC versus age and HRT usage in all age groups (p<0.05).
      Similarly, significant relationships were also found for the frequency of BAC
      versus OCA usage, HRT usage, hyperlipidemia and diabetes in age group of 40-49
      and in age group of 50-59, and for the frequency of BAC versus albuminuria in age
      group of 40-49, BAC versus history of myocardial infarction in age group of 59-59
      and over 60 years (p<0.05). The correlations were not significant for the
      relationships of BAC with OCA usage, hyperlipidemia, diabetes and albuminuria in
      women over 60 years (p>0.05). CONCLUSION: Most benign findings like BAC are not
      routinely reported during mammographic evaluation. Our study showed that,
      presence of BAC on mammography was strongly related to advancing age. However,
      these findings may signify a systemic risk and can be used as precautious
      indicators for undocumented systemic diseases, especially in premenopausal women.

PMID- 16890396
TI  - Cytotoxic evaluation of cubic boron nitride in human origin cultured cells.
AB  - The aim of this study was to evaluate the cytotoxicity of cubic boron nitride
      (cBN), a component of surgical cutting tools. The small quantities of cBN that
      typically remain on implants as a result of the manufacturing process may act as
      abrasives, injuring tissues surrounding the implant. To determine how cBN affects
      cells, we treated human neuroblastoma cells (NB-1) and human articular
      chondrocytes (nHAC-kn) with different concentrations of cBN powder and assessed
      cell growth and cell survival using the methyl-thiazol-tetrazolium (MTT) assay
      and a fluorescence probe assay. We also assessed the effects of tungsten carbide
      (WC) and cobalt (Co), two common components of joint implants, on cell growth and
      cell survival. Both cBN and WC moderately inhibited NB-1 and nHAC-kn cell growth.
      However, cBN and WC did not affect cell survival, even at high concentrations (40
      microg/ml). By contrast, Co affected cell survival, inducing cell death in both
      cell types at increasing concentrations. These results suggest that cBN may be
      less toxic than WC alloys containing Co.

PMID- 16890398
TI  - Reconceptualizing emetophobia: a cognitive-behavioral formulation and research
      agenda.
AB  - Fear of vomiting (emetophobia) is a poorly understood anxiety disorder, with
      little research published into its conceptualization or treatment. The current
      article uses established cognitive and behavioral models of other anxiety
      disorders as a basis from which to propose a detailed model of emetophobia. The
      model proposes that emetophobia results from a constellation of factors including
      a general anxiety-vulnerability factor, a tendency to somatize anxiety as
      gastrointestinal distress, a tendency to catastrophically misappraise nausea and
      other gastrointestinal symptoms, hypervigilance to gastrointestinal cues, beliefs
      about the unacceptability of vomiting, negatively reinforced avoidance behavior,
      and selective confirmation biases. A formulation-based treatment package for
      emetophobia is outlined, including arousal management skills,
      distraction/attention training, exposure and cognitive restructuring.

PMID- 16890397
TI  - Prediction errors of the Oklahoma Premorbid Intelligence Estimate-3 (OPIE-3)
      stratified by 13 age groups.
AB  - The Oklahoma Premorbid Intelligence Estimate-3 (OPIE-3) combines Wechsler Adult
      Intelligence Scale-3rd edition (WAIS-III) subtest raw scores (vocabulary,
      information, matrix reasoning, and picture completion) and demographic data
      (i.e., age, education, gender, ethnicity, and region) to predict FSIQ scores.
      Differences between OPIE-3 estimated FSIQ scores and actual FSIQ scores were
      compared across 13 age groups in a random sample (N=1201) of the WAIS-III
      standardization sample. There were mean differences in estimated FSIQ between age
      groups (P<.01). There was a trend that the OPIE-3 algorithms underestimated FSIQ
      for individuals 16-17 (2.7 points) and 80-89 years old (3.5 points). However, the
      differences in estimation errors were small and the percentage of individuals
      misclassified by more than 10 FSIQ points by age group was similar across groups.
      The OPIE-3(2ST), OPIE-3MR, and OPIE-3VOC yielded robust estimates of FSIQ across
      age groups in a neurologically intact sample. Limitations, particularly with
      individuals aged 16-17 and 85-89 years, are discussed.

PMID- 16890399
TI  - Anxiety disorders and workplace-related anxieties.
AB  - BACKGROUND: Workplace-related anxieties are often connected with sick leave.
      There are no established instruments which allow to assess this
      phenomenologically heterogeneous group of disorders. METHOD: One hundred and
      thirty-two psychosomatic inpatients were interviewed with a standardized
      diagnostic interview in respect to mental illnesses, especially primary anxiety
      disorders, and in addition in respect to different work-related anxiety
      disorders. RESULTS: Seventy-one percent of women and 54% of men complained about
      work-related anxiety. 20.5% of participants are suffering from work-related
      panic, 58% from work-related phobia, 34.1% from work-related social phobia, 39.4%
      from work-related generalized anxiety, and 1.5% from work-related PTSD. There is
      a moderate relation between mental disorders or primary anxiety disorders and
      work-related anxiety. Fourteen percent of the participants did only suffer from
      workplace-related anxiety and did not report any other anxiety disorder outside
      the workplace situation. CONCLUSION: There are various types of workplace-related
      anxieties. They are partly independent clinical phenomena deserving special
      diagnostic and therapeutic attention.

PMID- 16890400
TI  - Frequent appearance of novel protein-coding sequences by frameshift translation.
AB  - Genomic duplication, followed by divergence, contributes to organismal evolution.
      Several mechanisms, such as exon shuffling and alternative splicing, are
      responsible for novel gene functions, but they generate homologous domains and do
      not usually lead to drastic innovation. Major novelties can potentially be
      introduced by frameshift mutations and this idea can explain the creation of
      novel proteins. Here, we employ a strategy using simulated protein sequences and
      identify 470 human and 108 mouse frameshift events that originate new gene
      segments. No obvious interspecies overlap was observed, suggesting high rates of
      acquisition of evolutionary events. This inference is supported by a deficiency
      of TpA dinucleotides in the protein-coding sequences, which decreases the
      occurrence of translational termination, even on the complementary strand.
      Increased usage of the TGA codon as the termination signal in newer genes also
      supports our inference. This suggests that tolerated frameshift changes are a
      prevalent mechanism for the rapid emergence of new genes and that protein-coding
      sequences can be derived from existing or ancestral exons rather than from events
      that result in noncoding sequences becoming exons.

PMID- 16890401
TI  - Unexpected biochemical and pharmacogenetic consequences of SNPs and haplotypes: a
      cautionary tale for human molecular genetics and epidemiology.

PMID- 16890402
TI  - IGFL: A secreted family with conserved cysteine residues and similarities to the
      IGF superfamily.
AB  - We have discovered a family of small secreted proteins in Homo sapiens and Mus
      musculus. The IGF-like (IGFL) genes encode proteins of approximately 100 amino
      acids that contain 11 conserved cysteine residues at fixed positions, including
      two CC motifs. In H. sapiens, the family is composed of four genes and two
      pseudogenes that are referred as IGFL1 to IGFL4 and IGFL1P1 and IGFL1P2,
      respectively. Human IGFL genes are clustered together on chromosome 19 within a
      35-kb interval. M. musculus has a single IGFL family member that is located on
      chromosome 7. Further, evolutionary analysis shows a lack of direct orthology
      between any of the four human members and the mouse gene. This relationship
      between the mouse and the human family members suggests that the multiple members
      in the human complement have arisen from recent duplication events that appear
      limited to the primate lineage. Structural considerations and sequence
      comparisons would suggest that IGFL proteins are distantly related to the IGF
      superfamily of growth factors. IGFL mRNAs display specific expression patterns;
      they are expressed in fetal tissues, breast, and prostate, and in many cancers as
      well, and this pattern is consistent with that of the IGF family members.

PMID- 16890404
TI  - New necessary and sufficient conditions for absolute stability of neural
      networks.
AB  - This paper presents new necessary and sufficient conditions for absolute
      stability of asymmetric neural networks. The main result is based on a solvable
      Lie algebra condition, which generalizes existing results for symmetric and
      normal neural networks. An exponential convergence estimate of the neural
      networks is also obtained. Further, it is demonstrated how to generate larger
      sets of weight matrices for absolute stability of the neural networks from known
      normal weight matrices through simple procedures. The approach is nontrivial in
      the sense that non-normal matrices can possibly be contained in the resulting
      weight matrix set. And the results also provide finite checking for robust
      stability of neural networks in the presence of parameter uncertainties.

PMID- 16890403
TI  - Endocrine and cytokine responses in humans with pulmonary tuberculosis.
AB  - Endocrine responses during chronic infections such as lung tuberculosis are
      poorly characterized. Hormonal changes are likely to occur since some of the
      cytokines produced during this disease could affect endocrine mechanisms that, in
      turn, influence the course of infectious/inflammatory processes. A main purpose
      of this work was to study endocrine responses involving pituitary, adrenal,
      gonadal, and thyroid hormones in parallel to IFN-gamma, IL-10, and IL-6 levels in
      tuberculosis patients with different degree of pulmonary involvement. We have
      also studied whether products derived from peripheral immune cells obtained from
      the patients can affect the in vitro production of adrenal steroids. The
      population studied comprised HIV-negative newly diagnosed, untreated male
      patients with mild, moderate, and advanced lung tuberculosis, and matched,
      healthy controls. IFN-gamma, IL-10, and IL-6 levels were elevated in patients
      with tuberculosis. Dehydroepiandrosterone and testosterone levels were profoundly
      decreased and growth hormone levels were markedly elevated in patients, in
      parallel to modest increases in cortisol, estradiol, prolactin, and thyroid
      hormone concentrations. Supernatants of peripheral blood mononuclear cells
      obtained from the patients and stimulated in vitro with Mycobacterium
      tuberculosis antigens significantly inhibited dehydroepiandrosterone secretion by
      the human adrenal cell line NCI-H295-R. These results support the hypothesis that
      at least some of the endocrine changes observed in the patients may be mediated
      by endogenous cytokines. The endocrine profile of tuberculosis patients would
      favor a reduction of protective cell-mediated immunity and an exacerbation of
      inflammation leading to perpetuation of the lung injury and to the hypercatabolic
      condition that characterizes this disease.

PMID- 16890405
TI  - Uterine adenofibroma and endometrial stromal sarcoma associated with tamoxifen
      therapy: MR findings.
AB  - Tamoxifen therapy may result in a variety of endometrial proliferative lesions,
      including adenofibroma and endometrial stromal sarcoma (ESS). This report
      describes the MR findings of adenofibroma and ESS associated with tamoxifen
      therapy. When MRI demonstrates a uterine mass appearing as a heterogeneous mass
      in the endometrium or myometrium, adenofibroma and ECC must be considered as
      rare, but possible, diagnoses.

PMID- 16890406
TI  - Regulatory T cells in patients with systemic lupus erythematosus.
AB  - Regulatory T cells have an important role in the control of self-reactivity, and
      in the pathogenesis of autoimmune inflammatory conditions. The aim of this work
      was to perform a quantitative and functional analysis of regulatory T cells in
      patients with systemic lupus erythematosus (SLE). We studied twenty-three
      patients with SLE (19 active, 4 inactive), and twenty-seven healthy subjects as
      well as fifteen patients with rheumatoid arthritis (RA). The following cell
      subsets were analyzed in peripheral blood mononuclear cells by flow cytometry:
      CD4+CD25+, CD4+CD25(bright), CD4+Foxp3+ (Treg cells), CD8+CD28- (Ts cells),
      CD4+IL-10+ (Tr1 cells), and CD4+TGF-beta+ (Th3 cells). In addition, the in vitro
      suppressive activity of CD4+CD25+ lymphocytes was tested. We found no significant
      differences in the levels of all regulatory cell subsets studied in SLE patients
      compared to controls and RA patients. However, a defective regulatory function of
      CD4+CD25+T cells was observed in a significant fraction (31%) of patients with
      SLE. Our data indicate that although approximately one third of patients with SLE
      show an abnormal immunosuppressive function of Treg lymphocytes, their levels of
      the different regulatory T cell subsets in peripheral blood are not significantly
      different from those found in controls.

PMID- 16890407
TI  - Platelet-rich plasma does not improve bone regeneration around peri-implant bone
      defects--a pilot study in dogs.
AB  - The purpose of the present study was to evaluate the influence of platelet-rich
      plasma (PRP) on bone regeneration in dehiscence-type bone defects around dental
      implants. Ten male adult mongrel dogs were used. Three months after teeth
      extractions, an osteotomie for implantation and a buccal dehiscence defect were
      prepared on both sides of the jaws. Two dental implants with machined surfaces
      were placed on each implant site of the mandible. Dehiscences were randomly
      assigned to the following groups: (1) test (PRP) and (2) control. After 3 months
      animals were sacrificed; implants and adjacent hard tissues were processed for
      undecalcified sections. Bone-to-implant contact (BIC), bone density (BD) within
      the limits of implant threads, bone density (BO) and new bone area (NB) in a zone
      lateral to the implant, corresponding to bone defects, were obtained and
      measured. Inter group analysis (paired Student's t-test, alpha = 5%) demonstrated
      no statistically significant differences for any of the parameters when PRP was
      used (P > 0.05). Within the limits of the present study, it was concluded that
      platelet-rich plasma alone did not enhance bone regeneration for peri-implant
      defects.

PMID- 16890408
TI  - The role of 1H magnetic resonance spectroscopy in pre-operative evaluation for
      epilepsy surgery. A meta-analysis.
AB  - PURPOSE: We aimed to assess the additional pre-operative value of (1)H MRS in
      identifying the epileptogenic zone (EZ) for epilepsy surgery by performing a meta
      analysis considering publications from 1992 to 2003. METHODS: From an extensive
      computer and hand search 22 studies were included. For inclusion, studies had to
      report post-operative outcome and detailed diagnostic test results for each
      individual patient. Studies exclusively reporting on patients with brain tumors
      or on children were excluded. RESULTS: Great heterogeneity among studies
      regarding methodological and technical aspects and concerning evaluation and
      interpretation of data was observed. Only patients with intractable temporal lobe
      epilepsy were presented. Sixty-four percent of all patients and 72% of patients
      with good outcome had an ipsilateral MRS abnormality concordant with the EZ. The
      positive predictive value of all patients with ipsilateral MRS abnormality for
      good outcome was 82%. An odds ratio weighted by inverse variance showed a 4.891
      better chance of seizure free outcome [CI=1.965-12.172; Q=2.748; d.f.=5; critical
      chi2-value=11.07] in patients with an ipsilateral MRS abnormality when compared
      to patients with bilateral MRS abnormalities. Data for MRI-negative patients were
      conflicting. One study stressed a role for MRS in patients with bilateral
      hippocampal atrophy at MRI. CONCLUSIONS: MRS still remains a research tool with
      clinical potential. Our findings indicate the connection of ipsilateral MRS
      abnormality to good outcome. The ability for prediction of post-operative outcome
      may depend on the assessed population. Prospective studies limited to non
      localized ictal scalp EEG or MRI-negative patients are required for validation of
      these data.

PMID- 16890409
TI  - Reading impairment and visual processing deficits in schizophrenia.
AB  - Individuals with schizophrenia show magnocellular visual pathway abnormalities
      similar to those described in dyslexia, predicting that reading disturbance
      should be a common concomitant of schizophrenia. To date, however, reading
      deficits have not been well established, and, in fact, reading is often thought
      to be normal in schizophrenia based upon results of tests such as the WRAT, which
      evaluate single word reading. This study evaluated "real world" reading ability
      in schizophrenia, relative to functioning of the magnocellular visual pathway.
      Standardized psychoeducational reading tests and contrast sensitivity measures
      were administered to 19 patients and 10 controls. Analyses of between group
      differences were further refined by classification of participants into reading
      vs. non-reading impaired groups using a priori and derived theoretical models.
      Patients with schizophrenia, as a group, showed highly significant impairments in
      reading (p<0.04-p<0.001), with particular deficits on tests of rate,
      comprehension and phonological awareness. Between 21% and 63% of patients met
      criteria for dyslexia depending upon diagnostic model vs. 0-20% of the controls.
      The degree of deficit correlated significantly with independent measures of
      magnocellular dysfunction. Reading impairment in schizophrenia reaches the level
      of dyslexia and is associated with compromised magnocellular processing as
      hypothesized. Findings related to symptoms, functioning and recommendations for
      reading ability assessment are discussed.

PMID- 16890410
TI  - Impulsivity and BOLD fMRI activation in MDMA users and healthy control subjects.
AB  - The correlation between scores on the Barratt Impulsiveness Scale (BIS) and
      activation measured by functional magnetic resonance imaging in a dorsolateral
      prefrontal cortical (DLPFC) activating task was examined in 15 MDMA-using
      subjects and 19 controls. A significant correlation between BIS scores and DLPFC
      activation was found, supporting a role for the DLPFC in BIS-measured
      impulsivity.

PMID- 16890411
TI  - Cytochrome P450 (CYP) inhibition screening: comparison of three tests.
AB  - There are several different experimental systems for screening of in vitro
      inhibitory potency of drugs under development. In this study we compared three
      different types of cytochrome P450 (CYP) inhibition tests: the traditional single
      substrate assays, the fluorescent probe method with recombinant human CYPs, and a
      novel n-in-one technique. All major hepatic drug-metabolizing CYPs were included
      (1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, 3A4). Six compounds (sotalol,
      propranolol, citalopram, fluoxetine, oxazepam and diazepam) were selected for
      detailed comparisons. The IC50 values of each of these compounds were measured
      using the three assay types. The inhibitory potencies of these model drugs were
      generally within the same order of magnitude and followed similar inhibition
      profiles in all the assay types. Clinically observed inhibitory interactions, or
      lack thereof, were predictable with all three assays. Comparison of potencies of
      'diagnostic' inhibitors revealed also some notable differences between the
      assays, especially regarding CYP2E1. The potency of inhibitors towards CYP3A4 was
      dependent on the substrate and reaction measured. Generally all three assays gave
      reasonably comparable results, although some unexplained differences were also
      noted.

PMID- 16890412
TI  - Reciprocating dialysis tube method: periodic tapping improved in vitro
      release/dissolution testing of suppositories.
AB  - The reciprocating dialysis tube (RDT) method can be used for in vitro
      release/dissolution testing of suppositories and has been reported to show good
      in vitro and in vivo correlation. However, for suppositories with viscous
      excipients, the result remains variable and generally under-predicts in vivo
      absorption. The purpose of this study was to assess whether periodic tapping of
      the closure of the RDT could improve in vitro release testing of suppositories.
      Two commercially available acetaminophen suppositories (A and B) that showed
      characteristic release behavior under normal rectal temperatures (37 and 38
      degrees C) were chosen as test suppositories. In the absence of tapping,
      suppository A showed different release profiles at 37 and 38 degrees C, but the
      difference disappeared with periodic tapping. This finding was consistent with
      minimum temperature effect in the rectal absorption of suppository A in rabbits.
      Suppository B showed distinct release profiles at 37 and 38 degrees C
      irrespective of tapping, and the rectal absorption of suppository B in rabbits
      was affected by temperature. The test variability (CV% and ranges of release
      values) was substantially reduced in the presence of tapping. In conclusion, the
      addition of periodic tapping to RDT method developed in this study could improve
      in vitro release testing of suppositories.

PMID- 16890413
TI  - In vitro evaluation of antagonistic properties of Pseudomonas corrugata.
AB  - Pseudomonas corrugata, a soil bacterium originally isolated from a temperate site
      of Indian Himalayan Region (IHR) is examined for its antagonistic activities
      against two phytopathogenic fungi, Alternaria alternata and Fusarium oxysporum.
      Although the bacterium did not show inhibition zones due to production of
      diffusible antifungal metabolites, a reduction in growth between 58% and 49% in
      both test fungi, A. alternata and F. oxysporum, was observed in sealed Petri
      plates after 120 h of incubation due to production of volatile antifungal
      metabolites. Reduction in biomass of A. alternata (93.8%) and F. oxysporum
      (76.9%) in Kings B broth was recorded after 48 h of incubation in dual culture.
      The antagonism was observed to be affected by growth medium, pH and temperature.
      The reduction in fungal biomass due to antagonism of bacteria was recorded
      maximum in the middle of the stationary phase after 21 h of inoculation. The
      production of siderophore, ammonia, lipase and chitinase in growth medium by P.
      corrugata were considered contributing to the antagonistic activities of the
      bacterium.

PMID- 16890414
TI  - Intergeneric conjugation in holomycin-producing marine Streptomyces sp. strain
      M095.
AB  - Marine Streptomyces are potential candidates for novel natural products and
      industrial catalysts. In order to set up biosynthesis approach for a holomycin
      producing strain M095 isolated from Jiaozhou Bay, China, a genetic transformation
      system was established using intergeneric conjugation. The plasmid pIJ8600
      consists of an origin of replication for Escherichia coli, a phage integrase
      directing efficient site-specific integration in bacterial chromosome,
      thiostrepton-induced promoter and an attP sequence. Using E. coli ET12567
      (pUZ8002) carrying pIJ8600 as a conjugal donor, while it was mated with strain
      M095, pIJ8600 was mobilized to the recipient and the transferred DNA was also
      integrated into the recipient chromosome. The frequency of exconjugants was 1.9+/
      0.13x10(-4) per recipient cell. Analysis of eight exconjugants showed pIJ8600 was
      stable integrated at a single chromosomal site (attB) of the Streptomyces genome.
      The DNA sequence of the attB was cloned and shown to be conserved. The results of
      growth and antimicrobial activity analysis indicated that the integration of
      pIJ8600 did not seem to affect the biosynthesis of antibiotics or other essential
      amino acids. To demonstrate the feasibility of above gene transfer system, the
      allophycocyanin gene (apc) from cyanobacterium Anacystis nidulans UTEX625 was
      expressed in strain M095, and the results indicated heterologous allophycocyanin
      could be expressed and folded effectively.

PMID- 16890415
TI  - Recombinant expression of Garlic virus C (GARV-C) capsid protein in insect cells
      and its potential for the production of specific antibodies.
AB  - Garlic cultivars in Brazil are infected by a complex of viruses and for some
      virus species, such as the allexivirus, purification of the virions is sometimes
      cumbersume. To overcome this problem, recombinant expression of viral proteins in
      heterologous systems is an alternative method for producing antibodies. The
      capsid gene from Garlic virus C (GarV-C), an Allexivirus, was inserted into the
      genome of Autographa californica multiple nucleopolyhedrovirus (AcMNPV)
      generating the recombinant virus vSynGarV-C. The recombinant protein expression
      was confirmed by SDS-PAGE and western-blot of extracts from recombinant virus
      infected insect cells, where a protein band of approximately 32KDa was observed
      only in extracts from recombinant infected cells. This protein corresponded to
      the predicted size of the capsid protein of the GarV-C. A rabbit polyclonal
      antibody was raised against this protein, shown to be specific for the GarV-C
      protein in western-blot and dot-Elisa, however with a low titer.

PMID- 16890416
TI  - Prostaglandin E2 (PGE2) increases the number of rat bone marrow osteogenic
      stromal cells (BMSC) via binding the EP4 receptor, activating sphingosine kinase
      and inhibiting caspase activity.
AB  - Prostaglandin E(2) (PGE(2)) is bone-anabolic, i.e. stimulates bone formation and
      increases bone mass. In this study, we explored possible intracellular mechanisms
      of its increase of osteogenic cells in rat bone marrow. Adherent rat bone marrow
      cells were counted after 12-48 h or cultured for 21 days and mineralized nodules
      were counted. Also, apoptosis of marrow cells was measured after in vivo PGE(2)
      injection. PGE(2) (100 nM) increased 2-3 fold the number of adherent BMSC, an
      effect which was mediated via binding the EP(4) receptor since it was mimicked by
      forskolin and 11-deoxy-prostaglandin E(1) (PGE(1)) and was blocked by DDA and L
      161982 (EP(4) antagonist). PGE(2) stimulated sphingosine kinase (SPK) activity
      since its effects were blocked by DMS (SPK inhibitor) and mimicked by SPP (SPK
      product). PGE(2) reduced the activity of caspase-3 and -8 in BMSC and their
      inhibitors increased BMSC number and nodule formation. In vivo, PGE(2) prevented
      the increase in the apoptosis of bone marrow cells caused by indomethacin. We
      propose that PGE(2) exerts an anti-apoptotic effect on BMSC, thereby increasing
      their number and subsequent osteoblastic differentiation. Such an effect could
      explain how PGE(2) stimulates bone formation in vivo.

PMID- 16890417
TI  - Is impairment similar between arm and leg cranking exercise in COPD patients?
AB  - Impaired skeletal muscle function has been reported in patients with chronic
      obstructive disease (COPD), but such impairment is not homogenous and its
      distribution between the upper and the lower limbs is still unclear. The present
      study was designed to assess and compare upper and lower limb capacities in
      patients with moderate to severe COPD during incremental and constant-load
      exercises. Thirteen COPD patients of similar age with moderate to severe air flow
      limitation (FEV(1): 35%+/-5% predicted) and 19 healthy subjects were studied.
      Four sessions were organized: two incremental and two constant-load cycling
      exercises with arm or leg in randomized order. As observed in a previous study
      involving incremental and constant tests, power, VO(2), RER, VE, and HR were all
      significantly lower in the upper and lower limbs of patients with COPD than in
      healthy controls. In the healthy population, aerobic capacity and mechanical
      efficiency (ME) were lower in the course of arm exercises than in leg exercises.
      For the same relative workload, dyspnea and blood lactate production were higher
      during arm exercise. In contrast, no significant difference was observed between
      arm and leg capacities for any of these parameters in COPD patients. CONCLUSION:
      Although aerobic capacity is impaired in COPD patients, arm aerobic capacity is
      relatively preserved. Given the lack of significant difference between arm and
      leg capacities in COPD, we hypothesize that upper limb muscles are less
      compromised than lower limb muscles in this patient population.

PMID- 16890418
TI  - Elevated exhalation of hydrogen peroxide and circulating IL-18 in patients with
      pulmonary tuberculosis.
AB  - Mycobacteria are the strong stimulators of respiratory burst, resulting in
      production of reactive oxygen species and nitrogen intermediates. The aim of our
      study was to assess the concentration of hydrogen peroxide (H(2)O(2)) in expired
      breath condensate (EBC) and the serum level of interleukin-18 (IL-18) in patients
      with active pulmonary tuberculosis (TB) before introduction of chemotherapy and
      after 2 months of treatment. Sixteen patients, current cigarette smokers, with
      advanced pulmonary TB were enrolled into the study. As a control served two
      groups: I group--16 asymptomatic cigarette smokers, II group--17 healthy never
      smoked subjects. The level of H(2)O(2) in EBC was significantly higher in
      patients with TB (1.3+/-0.7 microM) as compared to cigarette are healthy
      nonsmoker subjects (0.4+/-0.1 and 0.2+/-0.1 microM, respectively, P<0.05). Two
      months of treatment significantly decreased the level of H(2)O(2) exhalation in
      TB patients (0.5+/-0.3 microM) to the value that was not different from that in
      asymptomatic smokers but was still higher than in never smoked subjects. Serum
      concentration of IL-18 in TB patients was higher than that found in both control
      groups either before and after antituberculous treatment (P<0.05). Exhaled
      H(2)O(2) did not correlate with circulating IL-18 in TB patients before or after
      treatment. These results demonstrated the occurrence of oxidative stress in the
      airways of TB patients completely attenuating after 2 months of successful
      antituberculous treatment.

PMID- 16890419
TI  - Smoking cessation practices of Dutch general practitioners, cardiologists, and
      lung physicians.
AB  - STUDY OBJECTIVES: To assess and compare the smoking cessation practices and
      smoking behavior of Dutch general practitioners (GPs), cardiologists, and lung
      physicians. METHODS: We conducted questionnaire surveys among a random sample of
      2000 Dutch GPs, all Dutch cardiologists (N=594), and all Dutch lung physicians
      (N=375). RESULTS: In total, 834 GPs (41.7%), 300 cardiologists (50.5%), and 258
      lung physicians (68.8%) filled out and returned the questionnaire. The prevalence
      of current smokers was 8.2% among GPs, 4.3% among cardiologists, and 3.5% among
      lung physicians. Of the pharmacological aids for smoking cessation, physicians
      recommended bupropion most frequently, followed by nicotine patches and nicotine
      gum. More lung physicians recommended the use of these three aids (67.0%, 36.3%
      and 18.2%, respectively) than GPs (65.7%, 18.7% and 9.8%, respectively), and than
      cardiologists (31.6%, 19.7% and 13.2%, respectively). A higher proportion of lung
      physicians (69.3%) had referred at least one smoker to a nurse for smoking
      cessation treatment than cardiologists (25%), and than GPs (11.3%). CONCLUSIONS:
      Based on this national survey, one may conclude that the prevalence of current
      smoking among Dutch physicians is relatively low and has further decreased since
      1988. Dutch GPs, cardiologists, and lung physicians mainly use interventions for
      smoking cessation that are easy to administer and are not very time consuming.
      Furthermore, more lung physicians than GPs and cardiologists recommend the use of
      bupropion, nicotine patch, and nicotine gum. When designing interventions for
      smoking cessation, one should take into account that physicians are often
      reluctant to provide interventions which demand much time. Therefore, intensive
      counseling of smokers who want to quit smoking may be more feasible for trained
      non-physicians, such as nurses.

PMID- 16890420
TI  - Change in plasma vascular endothelial growth factor during onset and recovery
      from acute mountain sickness.
AB  - There is an increasing body of evidence suggesting that altered vascular
      permeability may be an important component of the pathogenesis of acute mountain
      sickness (AMS). Vascular endothelial growth factor (VEGF) is a potent
      permeability factor subject to hypoxic regulation but its role in the
      pathogenesis of AMS is yet to be defined. We examined the relationship between
      plasma VEGF and AMS on ascent to high altitude and subsequent acclimatisation.
      Thirty-eight healthy lowlanders (median age 21, range 18-31) flew to La Paz,
      Bolivia (3650 m) on the Apex 2 research expedition. After 4-5 days
      acclimatisation, they ascended by vehicle over 90 min to the Chacaltaya
      laboratory (5200 m). We measured plasma VEGF in venous blood at sea level and at
      6 h and 3 and 7 days at 5200 m. AMS was scored using the Lake Louise consensus
      system. Using serial measurement of plasma VEGF at 5200 m, following partial
      acclimatisation at 3650 m, we demonstrated a highly significant change in VEGF
      levels (P<0.0005) with a rise in VEGF in approximately 80% of subjects by day 7
      at 5200 m. We found no evidence of an association between AMS and change in VEGF
      levels on ascent to either 3650 or 5200 m. We provide novel data of change in
      plasma VEGF levels during acclimatisation to high altitude, but our results do
      not support the hypothesis that circulating unbound VEGF is an important
      component of the pathogenesis of AMS.

PMID- 16890421
TI  - Asthma programme in Finland: comparison of adult asthma referral letters in 1994
      and 2001.
AB  - OBJECTIVES: The aim of the study was to evaluate the quality of asthma-related
      referral letters at the launch of the Asthma Programme in 1994 and 7 years later
      in 2001. METHODS: All referrals during 1 year (n=1121 in 1994, n=1136 in 2001) to
      one pulmonary department were screened in 2001. By the same inclusion criteria of
      asthma or suspicion of asthma, 624 letters (56% of all) from the year 1994 and
      452 (40% of all) from the year 2001 were selected. The quality of study letters
      was assessed against the previously developed asthma referral letter criteria.
      Comparison of the referral letter quality in 1994 and 2001 was made. RESULTS: The
      proportion of poor letters decreased from 63% in 1994 to 44% in 2001, while that
      of good letters increased from 7% to 22%. Graphics of peak flow follow-up
      measurements (14% vs. 40%) and spirometry with bronchodilatation test (5% vs.
      32%) were included significantly more often as an attachment. CONCLUSION: Lung
      functions are being measured more often in primary care, indication a more active
      detection of asthma. The number of asthma-related referrals in relation to all
      pulmonary consultation referrals decreased and their quality improved during the
      years of the Asthma Programme.

PMID- 16890422
TI  - Development of a novel DNA chip based on a bipolar semiconductor microchip
      system.
AB  - We have applied an integrated circuit photodiode array (PDA) chip system to a DNA
      chip. The PDA chip system, constructed using conventional bipolar semiconductor
      technology, acts as a solid transducer surface as well as a two-dimensional
      photodetector. DNA hybridization was performed directly on the PDA chip. The
      target DNA, the Bacillus subtilis sspE gene, was amplified by polymerase chain
      reaction (PCR). The 340-bp PCR product was labeled using digoxigenin (DIG). A
      silicon nitride layer on the photodiode was treated with poly-L-lysine to
      immobilize the DNA on the surface of the photodiode detection elements.
      Consequently, the surface of the photodiode detector became positively charged.
      An anti-DIG-alkaline phosphatase conjugate was reacted with the hybridized DIG
      labeled DNA. A color reaction was performed based on the enzymatic reaction
      between nitroblue tetrazolium/5-bromo-4-chloro-3-indolyl-phosphate (NBT/BCIP)
      staining solution and a DNA complex containing antibodies. A blue precipitate was
      formed on the surfaces of the photodiode detection elements. Successful
      quantitative analysis of the hybridized PCR products was achieved from the light
      absorption properties of the blue enzymatic reaction product that was produced
      after a series of reaction processes. Our DNA chip system avoids the complicated
      optical alignments and light-collecting optical components that are usually
      required for an optical DNA chip device. As a result, a simple, compact, portable
      and low-cost DNA chip is achieved. This system has great potential as an
      alternative system to the conventional DNA reader.

PMID- 16890423
TI  - Understanding the cell in terms of structure and function: insights from
      structural genomics.
AB  - Structural genomics programs are only now moving into the large-scale production
      phase, yet have already produced around 2000 protein structures. Through a
      widespread if not exclusive emphasis on structural novelty, our knowledge of the
      protein fold universe is improving rapidly. With this information comes the
      challenge of structure-based function annotation for the many target proteins
      about which little or nothing is known. Recent years have therefore seen the
      emergence of impressively diverse bioinformatics approaches to predict the
      function of a protein structure. Attention is now turning to means of combining
      these predictions with information from various other sources.

PMID- 16890424
TI  - Decreased expression of the adhesion molecule desmoglein-2 is associated with
      diffuse-type gastric carcinoma.
AB  - Desmoglein-2 (Dsg2) is one of the components of the cell-cell adherence junction.
      We previously reported that loss of heterozygosity at chromosome 18q12, on which
      the Dsg2 gene exists, is frequently found in diffuse-type gastric cancers. This
      study investigated the relationship between Dsg2 expression and diffuse-type
      gastric cancers. A total of 112 primary tumours resected from patients with
      gastric cancer were stained with a monoclonal antibody against Dsg2 and examined
      for correlations between the expression of Dsg2 and various clinicopathological
      factors, including loss of heterozygosity on chromosome 18q and prognosis. Dsg2
      is immunolocalised at cell-cell boundaries in normal gastric mucosa. Loss of Dsg2
      expression was observed in 33 of 112 gastric tumours. There was a statistically
      significant correlation between a decrease in Dsg2 staining and loss of tumour
      differentiation (P < 0.001), tumour macroscopic feature (P < 0.001) and
      peritoneal dissemination (P = 0.023), and Dsg2-negative staining was correlated
      significantly with loss of heterozygosity on chromosome 18q12 (P = 0.001). The
      prognosis of patients with Dsg2-negative tumours was significantly worse than
      that of those with Dsg2-positive tumours (log rank, P < 0.01), while multivariate
      analysis revealed that Dsg2 was not an independent prognostic factor. These
      findings suggest that decreased expression of Dsg2 is associated with diffuse
      type gastric cancers and poor prognosis in gastric carcinoma.

PMID- 16890425
TI  - Chewing gum and risk of oesophageal adenocarcinoma: a new hypothesis tested in a
      population-based study.
AB  - The aim of this study was to test the hypothesis that chewing gum is associated
      with risk of oesophageal and cardia adenocarcinoma. A Swedish nationwide,
      population-based, case-control study was conducted in 1995-1997. All patients
      were prospectively and uniformly documented and classified shortly after
      diagnosis. In all, 189 and 262 patients with oesophageal and cardia
      adenocarcinoma, respectively, and 820 population-based control subjects were
      interviewed. These patients together constituted 85% of eligible cases occurring
      in Sweden. Odds ratios (OR) with 95% confidence intervals (CI) were calculated by
      multivariable logistic regression with adjustment for plausible confounders.
      Regular users of chewing gum (P3 times/week for P6 months) were not at increased
      risk of oesophageal adenocarcinoma (OR 1.0, 95% CI 0.6-2.2), and no duration
      response relation was observed (P = 0.38). No association between regular gum
      chewing and cardia adenocarcinoma was found (OR 1.0, 95% CI 0.6-1.7),
      irrespective of duration of use (P = 0.56). In conclusion, with regard to risk of
      oesophageal or cardia adenocarcinoma, gum chewing seems harmless.

PMID- 16890426
TI  - Sequence of pig 17beta-hydroxysteroid dehydrogenase Type3 cDNA and its expression
      in mammalian cells.
AB  - 17beta-Hydroxysteroid dehydrogenase (17beta-HSD) Type3 is an NADPH-dependent
      membrane-bound enzyme that is specifically expressed in testis and catalyzes the
      conversion of androstenedione to testosterone. To date, the sequence of Type3
      enzymes has been clarified in humans, mice and rats; however, the sequence of the
      pig enzyme remains unknown. In this study, we determined the cDNA sequence of pig
      testicular 17beta-HSD Type3. PCR primers for partial pig testicular 17beta-HSD
      Type3 were designed from rat and human enzyme consensus sequences. Full-length
      cDNA was obtained by 3'- and 5'-RACE based on partial PCR products. The cDNA
      coding region was 933 bp in length, which is the same as the human enzyme, and
      shared 84.7% sequence identity with the human cDNA coding region. The monomer was
      estimated to have a molecular weight of 34,855 and to contain 310 amino acid
      residues. The predicted pig amino acid sequence showed 81.9, 75.5 and 72.9%
      sequence identity with the human, rat and mouse sequences, respectively. To
      elucidate 17beta-HSD Type3 activity, the expression vector pCMV/pig17beta-HSD3
      was established and transfected into human embryo kidney 293 cells. Subsequently,
      17beta-HSD activity (androstenedione conversion to testosterone) was strongly
      detected in cell lysates.

PMID- 16890428
TI  - 14Beta-hydroxy-10-deacetylbaccatin III as a convenient, alternative substrate for
      the improved synthesis of methoxylated second-generation taxanes.
AB  - This article describes a new, convenient, improved synthesis of the 2-debenzoyl-2
      m-methoxybenzoyl-7-triethylsilyl-13-oxo-14beta-hydroxybaccatin III 1,14
      carbonate, the key intermediate in the synthesis of two new second-generation
      antitumor taxanes.

PMID- 16890427
TI  - Synthesis and structural activity relationship of 11beta-HSD1 inhibitors with
      novel adamantane replacements.
AB  - A series of structurally novel and metabolically stable bridged bicyclic
      carbocycle and heterocycle adamantane replacements have been synthesized and
      biologically evaluated. Several of these compounds exhibit excellent human and
      mouse 11beta-HSD1 potency and 11beta-HSD2 selectivity.

PMID- 16890429
TI  - Toward intrinsically fluorescent proteomimetics: fluorescent probe response to
      alpha helix structure of poly-gamma-benzyl-L-glutamate.
AB  - A fluorescent probe (1), developed for recognition of alpha helical secondary
      structure, shows a large fluorescence change upon titration with the synthetic
      protein PBLG. Compared to fluorophores of similar size and shape, 1 displayed the
      smallest dissociation constant (K(D)=80microM) when titrated with PBLG. These
      preliminary studies are directed toward developing small molecule proteomimetics
      that have intrinsic fluorescence and are specific for helical-protein binding
      sites.

PMID- 16890430
TI  - Synthesis and biological evaluation of copper (II) complexes of sterically
      hindered o-aminophenol derivatives as antimicrobial agents.
AB  - Cu(II) complexes with 4,6-di(tert-butyl)-2-aminophenol (I) and 2-anilino-4,6
      di(tert-butyl)phenol (II) have been synthesized and characterized by means of
      elemental analysis, TG/DTA, FT-IR, UV-vis, ESR, and conductance measurements. The
      compounds I and II can coordinate in their singly deprotonated forms and behave
      as bidentate O,N-coordinated ligands; their CuL(2) complexes are characterized by
      CuN(2)O(2) coordination modes and square planar geometry. In vitro antimicrobial
      screening against Gram-positive and Gram-negative bacteria, yeasts, and moulds
      indicated that the compound I and its Cu(II) complex were more active than
      Questiomycin B, the compound II, and its Cu(II) complex.

PMID- 16890431
TI  - Synthesis of highly substituted dibenzo[b,f]azocines and their evaluation as
      protein kinase inhibitors.
AB  - Synthetic routes towards highly substituted eight membered ring heterocycles
      fused to aryl rings such as the dibenzo[b,f]azocine system are still lacking.
      Herein, we present a convenient convergent synthetic route towards this
      heterocyclic class of compounds with possible variations at positions 4, 7, and
      11. One member of a library of dibenzo[b,f]azocines with different substituents
      at position 11 was identified to inhibit protein kinase A activity
      (IC(50)=122microM) but not protein kinase C.

PMID- 16890432
TI  - Chiral recognition by fluorescent chemosensors based on N-dansyl-amino acid
      modified cyclodextrins.
AB  - Four kinds of N-dansyl-amino acid-modified beta-cyclodextrins (beta-CDs) were
      prepared as fluorescent chemosensors for chiral discrimination. The use of an
      amino acid as a spacer improved binding affinities and chiral discrimination
      abilities of the chemosensors. N-dansyl-l-Phe-modified beta-CD showed high d
      selectivity for norbornane derivatives and N-dansyl-d-Phe-modified beta-CD showed
      high l-selectivity for menthol. Microcalorimetric titration results indicate that
      the chemosensors selectively accommodate the enantiomer that induces the least
      unfavorable entropy change on making an inclusion complex.

PMID- 16890433
TI  - Synthesis of N1-arylidene-N2-quinolyl- and N2-acrydinylhydrazones as potent
      antimalarial agents active against CQ-resistant P. falciparum strains.
AB  - A series of N1-arylidene-N2-quinolyl- and N2-acrydinylhydrazones were synthesized
      and tested for their antimalarial properties. These compounds showed remarkable
      anti-plasmodial activity in vitro especially against chloroquine-resistant
      strains. Their potent biological activity makes them promising lead structures
      for the development of new antimalarial drugs.

PMID- 16890434
TI  - Novel C-3 N-urea, amide, and carbamate dihydroindazolo[5,4-a]pyrrolo[3,4
      c]carbazole analogs as potent TIE-2 and VEGF-R2 dual inhibitors.
AB  - A novel series of C-3 urea, amide, and carbamate fused dihydroindazolocarbazole
      (DHI) analogs are reported as highly potent dual inhibitors of TIE-2 and VEGF-R2
      receptor tyrosine kinases with excellent cellular potency. Structure-activity
      relationship (SAR) studies indicate the optimal N-13 alkyl substitutions are n
      propyl and i-butyl. The isopropyl carbamate 39 displayed good dual enzyme, cell
      potency, and rat pharmacokinetic properties for advancement to in vivo
      evaluation.

PMID- 16890435
TI  - Structure-activity relationships of novel antibacterial translation inhibitors:
      3,5-diamino-piperidinyl triazines.
AB  - Structure-activity relationships of the 3,5-diamino-piperidinyl triazine series,
      a novel class of bacterial translation inhibitors, are described. Optimization
      was focused on the triazine C-4 position in which aromatic substituents that
      contained electron-withdrawing groups led to potent inhibitors. The initial lack
      of antibacterial activity was correlated with poor cellular penetration. Whole
      cell antibacterial activity was achieved by linking additional aromatic moieties
      at the triazine C-4 position.

PMID- 16890436
TI  - Aza-stilbenes as potent and selective c-RAF inhibitors.
AB  - The synthesis of several novel aza-stilbene derivatives was carried out. The
      compounds were tested for their c-RAF enzyme inhibition. Compound 27 possesses
      significant potency against c-RAF and demonstrates selectivity over other protein
      kinases. A hypothesis for the binding mode, activity, and selectivity is
      proposed.

PMID- 16890437
TI  - Pyrrolidine bis-cyclic guanidines with antimicrobial activity against drug
      resistant Gram-positive pathogens identified from a mixture-based combinatorial
      library.
AB  - The rapid rise in antibiotic-resistant Gram-positive bacterial infections
      prompted us to explore the development of novel strategies for synthesis of large
      chemical libraries amenable to high-throughput screening for antimicrobial
      activities. Here we report the solid-phase synthesis of a 738,192 member
      pyrrolidine bis-cyclic guanidine chemical library with 26 different amino acids
      at three positions of diversity and 42 carboxylic acids at the fourth position.
      This synthetic combinatorial library was developed for positional scanning and
      screened for bacteriostatic and bactericidal activities against the important
      human pathogen methicillin-resistant Staphylococcus aureus (MRSA). The eight
      compound mixtures exhibiting bactericidal activity (10 microg/mL) against MRSA
      were used to direct the synthesis of 36 individual compounds that were then
      screened for activity against MRSA, vancomycin-resistant Enterococcus faecalis
      (VRE), and two Gram-negative bacterial species. At least 20 individual compounds
      were bactericidal for MRSA at 2.5 microg/mL, with a subset of these compounds
      showing bactericidal activities (10 microg/mL) against the other species tested.
      This approach demonstrates the capability to synthesize and screen a complex
      library to yield promising antimicrobials that address a critical need for novel
      infectious disease therapeutics.

PMID- 16890438
TI  - Patient empowerment in intensive care--an interview study.
AB  - Intensive care patients often experience a lack of control, as well as inner
      chaos. Experiences from intensive care can continue to affect patients for a long
      time. Empowerment is a positive and dynamic process that focuses on people's
      strengths, rights and abilities. It takes on different expressions for different
      people in different environments and must be described by the people involved.
      The aim of this study was to describe patient empowerment in an intensive care
      situation. The study was based on open-ended interviews with 11 patients in two
      intensive care units. The interviews were analysed according to the empirical
      phenomenological psychological method. The results showed that patient
      empowerment in intensive care consists of strengthening and stimulating the
      patients' own inherent joy of life and will to fight. A positive environment that
      encouraged feelings of value and motivation and in which the patient felt safe,
      received additional care and participated as he/she wished had a positive
      influence.

PMID- 16890439
TI  - Phagocyte-derived reactive species: salvation or suicide?
AB  - Activated phagocytes produce "reactive oxygen, halogen and nitrogen species" that
      help to kill some types of microorganism. How these species destroy
      microorganisms remains, however, an enigma: both direct oxidative damage and
      indirect damage (whereby reactive species promote the actions of other
      antibacterial agents) are involved, and no single mechanism is likely to account
      for the killing of all microorganisms. Phagocyte-derived reactive species are
      known to injure human tissues and to contribute to inflammation. Recently,
      however, we have learned that they can also be anti-inflammatory by modulating
      the immune response. These data have implications for the proposed use of
      antioxidants to treat inflammation.

PMID- 16890440
TI  - Non-coding RNA in fly dosage compensation.
AB  - Dosage compensation modulates global expression of an X chromosome and is
      necessary to restore the balance between X-chromosome and autosome expression in
      both sexes. A central question in the field is how this regulation is directed.
      Large non-coding RNAs, such as Xist in mammals and roX in flies, have pivotal
      roles in targeting chromosome-wide modification for dosage compensation. Several
      recent studies in Drosophila provide new insight into the principles of X
      chromosome recognition and the function of non-coding RNA in this process.

PMID- 16890441
TI  - Building functional modules from molecular interactions.
AB  - The main reaction pathways in the living cell are carried out by functional
      modules--namely, macromolecular machines with compact structure or ensembles that
      change their composition and/or organization during function. Modules define
      themselves by spatial sequestration, chemical specificity and a characteristic
      time domain within which their function proceeds. On receiving a specific input,
      modules go through functional cycles, with phases of increasing and decreasing
      complexity of molecular interactions. Here, we discuss how such modules are
      formed and the experimental and theoretical approaches that can be used to
      investigate them, using examples from polynucleotide-protein interactions,
      vesicle transport and signal transduction to illustrate the underlying
      principles. Further progress in this field, where systems biology and
      biochemistry meet, will depend on iterative validation of the experimental and
      theoretical approaches.

PMID- 16890442
TI  - Pore-forming scissors? A first structural glimpse of gamma-secretase.
AB  - Amyloid plaques, which are composed of amyloid-beta peptide (Abeta), signify
      Alzheimer's disease pathology. Secretases generate Abeta by processing the beta
      amyloid precursor protein. gamma-Secretase, a complex comprising four different
      proteins, liberates Abeta from its precursor by intramembrane proteolysis. The
      first impression of the shape of gamma-secretase has recently been revealed by
      electron microscopy. It indicates a spherical transmembrane particle with an
      interior chamber that, presumably, accommodates its catalytic residues, and two
      openings that might be exit sites for the cleavage products.

PMID- 16890443
TI  - Themes in ssDNA recognition by telomere-end protection proteins.
AB  - The ends of eukaryotic linear chromosomes are unique structures that require
      special management by the cell. If left unattended, the ends are inappropriately
      processed, leading to genomic instability and problems with proliferation.
      Telomeres are specialized nucleoprotein structures that restore chromosome
      stability by protecting and maintaining chromosome ends. Proper telomere function
      is facilitated, in part, by the telomere-end protection (TEP) family of proteins,
      which targets the 3' single-stranded (ss) overhang region of the telomere via a
      specialized ssDNA-binding domain (DBD). With the recent availability of the
      structures of these DBDs, the ssDNA-binding characteristics of TEP proteins can
      be compared and the common underlying mechanisms of ssDNA recognition identified,
      thus providing insights into telomere function.

PMID- 16890444
TI  - Structure-activity relationship study of flavone compounds with anti-HIV-1
      integrase activity: a density functional theory study.
AB  - Human immunodeficiency virus type-1 integrase (HIV-1 IN) is an essential enzyme
      for effective viral replication. Flavone compounds have been very much studied
      due to their activity during the inhibition process of HIV-1 IN. In this study,
      we employed density functional theory (DFT) using the B3LYP hybrid functional to
      calculate a set of molecular properties for 32 flavonoid compounds with anti-HIV
      1 IN activity. The stepwise discriminant analysis (SDA), principal component
      analysis (PCA) and hierarchical cluster analysis (HCA) methods were employed to
      reduce dimensionality and investigate possible relationship between the
      calculated properties and the anti-HIV-1 IN activity. These analyses showed that
      the molecular hydrophobicity (ClogP), charge on atom 11 and electrophilic index
      (omega) are responsible for the separation between anti-HIV-1 IN active and
      inactive compounds.

PMID- 16890445
TI  - Design, synthesis and antibacterial activity of novel 1,3-thiazolidine pyrimidine
      nucleoside analogues.
AB  - The synthesis of a new class of 1,3-thiazolidine nucleoside analogues in which
      furanose oxygen atom was replaced with nitrogen atom and 2'-carbon atom with
      sulfur atom is described. N-tert-butoxycarbonyl-2-acyloxy-4-trityloxymethyl-1,3
      thiazolidine was coupled with the pyrimidine bases like uracil, thymine, etc. in
      the presence of lewis acids stannic chloride or trimethyl silyl triflate
      following Vorbruggen procedure. The antibacterial activity of the novel 1,3
      thiazolidine pyrimidine nucleoside analogues is highlighted. All compounds (7a-e)
      with free NH group in the pyrimidine moiety showed significant biological
      activity against all the standard strains used and in that compounds 7d and 7e
      showed significant activity against 14 human pathogens tested.

PMID- 16890446
TI  - Anthracene based base-discriminating fluorescent oligonucleotide probes for SNPs
      typing: synthesis and photophysical properties.
AB  - 2- and 9-Anthracenecarboxamide labeled 2'-deoxyuridines were synthesized and
      their photophysical properties were examined. These oligonucleonucleotide probes
      are capable of detecting adenine base on a target DNA sequence. It was also found
      that 2-anthracene based oligonucleotide probe is more efficient than the
      corresponding 9-anthracene based oligonucleotide in the application for DNA chip
      based SNP detection, due to its longer emission wavelength and high fluorescence
      intensity.

PMID- 16890447
TI  - Implementation of the TDCR liquid scintillation method at CNEA-LMR, Argentina.
AB  - During the last two years, a triple-to-double coincidence ratio (TDCR) system was
      assembled and adjusted at the CNEA-LMR, Argentina. The new counting system will
      add complementary capabilities to the absolute measurements section of the CNEA
      LMR. This work describes its implementation and validation. Several checks and a
      set of beta-emitting standard solutions were used in order to perform the
      validation experiments. In preliminary measurements, a 3H LNHB solution with
      reference activity concentration of (119.7+/-0.9) kBq/g on 11 November 2003 was
      used. The CNEA-LMR TDCR counter gave, at the same reference date, an activity
      concentration of (120+/-1) kBq/g. Results and improvements are presented in
      detail. Concerning the asymmetry of the system, the quantum efficiency of the
      three photomultiplier tubes was studied for different operating conditions of the
      focusing voltage. The counter also includes an automatic system to change the
      efficiency by defocusing the photomultipliers and on the other hand, it was
      coupled to a HPGe detector to also measure beta-gamma coincidences.

PMID- 16890448
TI  - Pre-visual detection of iron and phosphorus deficiency by transformed reflectance
      spectra.
AB  - Reflectance spectroscopy and strategies for spectral analysis over the visible
      range from 380 to 780 nm were used to provide diagnostic information on iron (Fe)
      and phosphorus (P) status of Brassica chinensis L. var parachinensis (Bailey)
      grown under hydroponics conditions. Leaf reflectance (R) spectra were collected
      and normalized inner reflectance (NR(I)) spectra were calculated. The regression
      coefficients (B-matrix) and variable importance for projection (VIP) in partial
      least squares regression were used to determine important wavelengths that
      correlate with total chlorophyll (Chl) content. No single wavelength that showed
      good correlation with Chl content was found. Therefore, NR(I) was transformed
      into CIELAB color values, which simplified the whole visible spectrum into three
      values. Our results showed that upon Fe deprivation, plants entered into a
      deficiency state very rapidly, highlighting the importance of early diagnosis.
      The direct effect of Fe on leaf Chl content allowed CIELAB color values to be
      used for pre-visual detection of Fe deficiency 2 days before the appearance of
      visually distinguishable morphological changes. On the other hand, P-deprived
      plants showed a marked decline in cellular P levels but remained above critical
      threshold concentrations after 7 days. The Chl content was not affected by the
      leaf P content and CIELAB color values showed no difference with control plants.

PMID- 16890449
TI  - Retinal vascular manifestations of metabolic disorders.
AB  - Metabolic diseases have profound effects on the structure and function of the
      retinal circulation. The recent development of retinal photography and digital
      imaging has enabled more precise documentation of diabetic retinopathy, as well
      as other retinal microvascular changes, such as retinal arteriolar narrowing,
      venular dilation and isolated retinopathy signs in nondiabetic individuals. These
      retinal microvascular signs have been shown to be associated with long-term risks
      of type 2 diabetes and hypertension, components of the metabolic syndrome (e.g.
      obesity, dyslipidemia), and a range of macro- and micro-vascular conditions (e.g.
      stroke, cardiovascular mortality). There is evidence that endothelial dysfunction
      and inflammation might be possible mechanisms involved in the development of
      various retinal microvascular changes in patients with diabetes, hypertension and
      other metabolic disorders. Further understanding of how these processes influence
      the retinal vasculature might help to elucidate the diverse vascular
      manifestations of metabolic diseases.

PMID- 16890450
TI  - Inverted rhythm of melatonin secretion in Smith-Magenis syndrome: from symptoms
      to treatment.
AB  - Smith-Magenis syndrome (SMS) is a mental retardation syndrome with distinctive
      behavioral characteristics, dysmorphic features and congenital anomalies ascribed
      to an interstitial deletion of chromosome 17p11.2. Severe sleep disturbances and
      maladaptative daytime behavior have been linked to an abnormal circadian
      secretion pattern of melatonin, with a diurnal instead of nocturnal secretion of
      this hormone. SMS provides a demonstration of a biological basis for sleep
      disorder in a genetic disease. Considering that clock genes mediate the
      generation of the circadian rhythm, haploinsufficiency for a circadian system
      gene, mapping to chromosome 17p11.2 might cause the inversion of the melatonin
      circadian rhythm in SMS. The disorder of circadian timing in SMS might also
      affect the entrainment pathway (retinohypothalamic tract), pacemaker functions
      (suprachiasmatic nucleus) or synthesis and release of melatonin by the pineal
      gland. Elucidating pathophysiological mechanisms of behavioral phenotypes in
      genetic disease can provide an original therapeutic approach in SMS: blockade of
      endogenous melatonin production during the day combined with exogenous melatonin
      administration in the evening.

PMID- 16890451
TI  - Seven-transmembrane receptor signalling and ERK compartmentalization.
AB  - Vast numbers of extracellular signalling molecules exert effects on their target
      cells by activation of a relatively limited number of mitogen-activated protein
      kinase (MAPK) cascades, raising the question of how specificity is achieved. To a
      large extent, this appears to be attributable to differences in kinetics and
      compartmentalization of MAPK protein activation that are dictated by MAPK
      associated proteins serving as scaffolds, anchors, activators or effectors. Here,
      we review spatiotemporal aspects of signalling via the Ras-Raf-extracellular
      signal-regulated kinase pathway, emphasizing recent work on roles of arrestins as
      scaffolds and transducers for seven transmembrane receptor signalling.

PMID- 16890452
TI  - Production of IL-1Ra by human mononuclear blood cells in vitro: influence of
      serum factors.
AB  - In vitro cell culture models that measure cytokine production can be of great
      value when analyzing regulatory mechanisms underlying various pathological
      conditions. However, testing the function of peripheral blood cells has to take
      into consideration that serum factors are likely to be of importance in
      maintaining their function. Interleukin-1 receptor antagonist (IL-1Ra) is a
      cytokine of key importance in immune regulation and is believed to be involved in
      numerous pathological processes, such as autoimmunity and cancer. We investigated
      the influence of normal, human serum on spontaneous production of IL-1Ra by human
      peripheral blood mononuclear cells (PBMC) in vitro. IL-1Ra production in vitro
      spanned over a wide range of concentrations, which could be attributed to a
      combined effect of both cellular parameters and properties of the serum used. The
      production of IL-1Ra in vitro could be correlated to the level of immobilized
      IgG, especially IgG1 and IgG3, which is adsorbed from the serum and bound to the
      tissue culture wells during culture. However, the amount of serum IgG adsorbed to
      the tissue culture wells could not necessarily be predicted based on the serum
      concentration of IgG.

PMID- 16890453
TI  - The role of conformation on electron capture dissociation of ubiquitin.
AB  - Effects of protein conformation on electron capture dissociation (ECD) were
      investigated using high-field asymmetric waveform ion mobility spectrometry
      (FAIMS) and Fourier-transform ion cyclotron resonance mass spectrometry. Under
      the conditions of these experiments, the electron capture efficiency of ubiquitin
      6+ formed from three different solution compositions differs significantly,
      ranging from 51 +/- 7% for ions formed from an acidified water/methanol solution
      to 88 +/- 2% for ions formed from a buffered aqueous solution. This result
      clearly indicates that these protein ions retain a memory of their solution-phase
      structure and that conformational differences can be probed in an ECD experiment.
      Multiple conformers for the 7+ and 8+ charge states of ubiquitin were separated
      using FAIMS. ECD spectra of conformer selected ions of the same charge states
      differ both in electron capture efficiency and in the fragment ion intensities.
      Conformers of a given charge state that have smaller collisional cross sections
      can have either a larger or smaller electron capture efficiency. A greater
      electron capture efficiency was observed for ubiquitin 6+ that has the same
      collisional cross section as one ubiquitin 7+ conformer, despite the lower charge
      state. These results indicate that the shape of the molecule can have a greater
      effect on electron capture efficiency than either collisional cross section or
      charge state alone. The cleavage locations of different conformers of a given
      charge state were the same indicating that the presence of different conformers
      in the gas phase is not due to difference in where charges are located, but
      rather reflect conformational differences most likely originating from solution.
      Small neutral losses observed from the singly- and doubly-reduced ubiquitin 6+ do
      not show a temperature dependence to their formation, consistent with these ions
      being formed by nonergodic processes.

PMID- 16890454
TI  - Measuring MAP kinase activity in immune complex assays.
AB  - I present an overview of published methods for measuring mitogen activated
      protein (MAP) kinase activity on endogenous associated substrates, exogenously
      added substrates as well as determination of activation loop phosphorylation as a
      read-out of kinase activity in vivo. Detailed procedures for these assays are
      given for two MAP kinases (MAPKs) Fus3 and Kss1 and compared with other published
      protocols, including the protocols for Hog1 and Mpk1 MAPKs. Measuring kinase
      activity in immune complex assays can serve as an approach for identification of
      potential substrates of protein kinases as well as for detecting other kinase
      associated proteins.

PMID- 16890455
TI  - The three-dimensional structure of trichocyte (hard alpha-) keratin intermediate
      filaments: the nature of the repeating unit.
AB  - Recently, the spatial distribution of the crosslinks induced between lysine
      residues in trichocyte (alpha-) keratin intermediate filaments (IF) using
      disulfosuccinimidyl tartrate was analyzed in detail and the results used to
      provide information about the three-dimensional structure of the IF [Fraser,
      R.D.B., Parry, D.A.D., 2005. The three-dimensional structure of trichocyte (hard
      alpha-) keratin intermediate filaments: features of the molecular packing deduced
      from the sites of induced crosslinks. J. Struct. Biol. 151, 171-181.] The
      presence of small amounts of 0--> +/-4 crosslinkages between molecular strands
      four distant in the network implied that the three-dimensional network of
      interacting molecules must be deeply puckered, but no specific suggestions were
      made about the nature of the puckering. Whilst it was recognized that there may
      be more than one type of molecular environment in the structural repeat the
      initial analysis was confined to the simplest case in which all molecules had the
      same environment, that is to say the asymmetric unit comprised a single molecule.
      Further studies reported here suggest that it is likely that the asymmetric unit
      consists of at least two and possibly as many as four molecules and the
      implications of this for modeling the structure of trichocyte IF are discussed.

PMID- 16890456
TI  - Similar response of agonist and antagonist muscles after eccentric exercise
      revealed by electromyography and mechanomyography.
AB  - The purpose of this study was to investigate the influence of eccentric
      contractions (ECC) on the biceps (BB) and triceps brachii (TB) muscles during
      maximal voluntary contraction (MVC) of elbow flexors using electrical (EMG) and
      mechanomyographical activities (MMG). Each of 18 male students performed 25
      submaximal contractions (50% MVC) of the elbow flexors. Root mean square
      amplitude (RMS) and median frequency (MDF) were calculated for the EMG and MMG
      signals recorded during MVC. All measurements were taken before, immediately
      after, 24, 48, 72, and 120 h post-ECC from the BB and TB muscles. MVC was reduced
      by 34% immediately after exercise and did not return to the resting value within
      120 h (P0.05). The EMG MDF decreased significantly (P< or =0.05) in both muscles
      after ECC. The MMG RMS at 24h, 48, 72 and 120 h post-ECC was significantly lower
      compared to that recorded immediately after ECC in both muscles (P< or =0.05).
      The present research showed that (i) there were similar changes in electrical and
      mechanical activities during MVC after submaximal ECC in agonist and antagonist
      muscles suggesting a common drive controlling the agonist and antagonist
      motoneuron pool, (ii) the ECC induced different changes in EMG than in MMG
      immediately after ECC and during 120 h of recovery that suggested an increased
      tremor and contractile impairments, i.e., reduced rate of calcium release from
      the sarcoplasmic reticulum (acute effect), and changes in motor control
      mechanisms of agonist and antagonist muscles, and increased muscle stiffness
      (chronic effect).

PMID- 16890457
TI  - Location of innervation zone determined with multichannel surface
      electromyography using an optical flow technique.
AB  - Multichannel surface electromyography has developed towards more channels and
      higher spatial resolution. This allows the study of multichannel electromyograms
      as images of the potential distribution on the skin. In this paper, a method that
      estimates the motion of the potential distribution using an optical-flow-based
      technique is introduced. The optical flow is a vector field that describes how
      images change with time. The aim of this study was to introduce a new method for
      innervation zone (IZ) localization and to evaluate its performance. The new
      method was compared with a method that uses the position of the lowest root-mean
      square (RMS) value in an electrode array as an estimate of the IZ localization.
      Comparisons were made with both simulated signals and with recorded multichannel
      electromyogram signals. Simulations showed that the methods performed similarly
      for high signal-to-noise ratio (SNR) and that the optical-flow-based method was
      superior for lower SNR. When the experimental signals were used, localization
      with the optical-flow-based method gave a mean absolute deviation of 2.4mm from
      the location given by an expert group. The lowest RMS method gave a significantly
      higher deviation (13.6mm). Due to the low computational complexity of the optical
      flow algorithm it is possible to get the estimations of the IZ localization in
      real time.

PMID- 16890458
TI  - Analyzing gastrocnemius EMG-activity and sway data from quiet and perturbed
      standing.
AB  - In an experiment, we combined force plate measurements and surface EMG in
      studying quiet and perturbed standing, involving MS (Multiple sclerosis) and
      controls. The aim of this paper is to report the results thus obtained on the
      relation between filtered gastrocnemius (GA) EMG and the anterior-posterior
      center-of-pressure (A/P COP) coordinate. The main finding is the good
      correspondence between A/P COP and the filtered GA EMG in the low frequency
      range. The EMG envelope was calculated using a zero-lag filter. Combining this
      with time shifts around 250-350 ms produced a high correlation (85.5+/-8.4%)
      between the GA-EMG envelope and the A/P COP. This EMG-COP relation was closest
      when using a low cut-off frequency value around 1 Hz in calculating the EMG
      envelope. Based on this filtering procedure we estimated the average EMG-COP time
      shift to be 283+/-43 ms between the GA-EMG envelope and A/P COP (which "lags"
      behind EMG envelope). This shift is consistent with the 1 Hz cut-off and phase
      shift produced by a corresponding critically damped second-order filter, and is
      about twice the corresponding twitch time. These results suggest that GA is to a
      large extent responsible for the phasic control of the anterior-posterior balance
      during quiet standing. A small difference (p<0.03) was found between mean time
      shift thus obtained for controls (n=4) and MS (n=6) while sway area showed a
      major difference (p<0.01). The paper also compares three alternative filters for
      numerical calculation of the EMG-envelope.

PMID- 16890459
TI  - Electroencephalographic characterization of scopolamine-induced convulsions in
      fasted mice after food intake.
AB  - The present study was conducted to evaluate scopolamine-induced convulsions in
      fasted mice after food intake effects on the cortical electroencephalogram (EEG).
      Continuous EEG recordings were taken with Neuroscan for 10 min in freely moving
      mice with six chronic cortical electrode implants. Animals were weighed and
      deprived of food for 48 h. EEG recordings were taken at the 24th and 48th hour
      after their food deprivations. Later, all animals were treated with saline or
      scopolamine of 3mg/kg i.p. and EEG recordings were repeated for 10 min. Twenty
      minutes later, they were given food pellets and were allowed to eat ad libitum.
      All animals were observed for 60 min to determine the incidence and onset of
      convulsions and EEG recordings were taken simultaneously. The present results
      demonstrate that food deprivation causes differences in EEG in the elapsed time.
      The changes in EEG induced after food deprivation become different with
      scopolamine administration. In scopolamine treatment group, eating caused a
      series of high-voltage polyspikes and synchronized spikes with a predominant
      frequency in the 1-3 Hz range and fast activity that represents a typical
      epileptiform manifestation. It was concluded that the EEG properties and the
      behavioral patterns of these convulsions are in accordance with each other.

PMID- 16890460
TI  - Validation of the Dutch version of the Hip disability and Osteoarthritis Outcome
      Score.
AB  - INTRODUCTION: The Hip disability and Osteoarthritis Outcome Score (HOOS) was
      constructed in Sweden; this questionnaire has proved to be valid for persons with
      hip disability with or without hip osteoarthritis (OA) and with high demands of
      physical function. OBJECTIVE: The objective of this study was to evaluate the
      internal consistency, reliability, construct validity, and floor and ceiling
      effects of the Dutch version of the HOOS questionnaire. PATIENTS AND METHODS:
      After translation with a forward/backward protocol, 74 hip arthroplasty patients
      and 88 hip OA patients filled in the Dutch HOOS, as well as a Short Form-36 (SF
      36), an Oxford Hip Score (OHS) and a VAS-pain questionnaire. RESULTS: The Dutch
      version of the HOOS questionnaire achieved excellent scores in all of the
      clinimetric properties. CONCLUSION: The Dutch HOOS questionnaire has a good
      internal consistency and reliability. Moreover, the construct validity is good
      and no floor and ceiling effects were found. The HOOS is a good instrument for
      patients with different stadia of hip OA.

PMID- 16890461
TI  - Longitudinal study of magnetic resonance imaging and standard X-rays to assess
      disease progression in osteoarthritis.
AB  - OBJECTIVE: To investigate, over 1-year, the relationship between X-ray and
      magnetic resonance imaging (MRI) findings in patients with knee osteoarthritis
      (OA). METHODS: Sixty-two osteoarthritic patients (46 women) were followed for 1
      year. At baseline and after 1 year, volume and thickness of cartilage of the
      medial tibia, the lateral tibia and the femur were assessed by MRI. A global
      score from the multi-feature whole-organ MRI scoring system (WORMS) was
      calculated for each patient at baseline and after 1 year. This score combined
      individual scores for articular cartilage, osteophytes, bone marrow abnormality,
      subchondral cysts and bone attrition in 14 locations. It also incorporated scores
      for the medial and lateral menisci, anterior and posterior cruciate ligaments,
      medial and lateral collateral ligaments and synovial distension. Lateral and
      medial femoro-tibial joint space width (JSW) measurements, performed by digital
      image analysis, were assessed from fixed-flexion, postero-anterior knee
      radiographs. RESULTS: One-year changes in medial femoro-tibial JSW reach 6.7
      (20.5) % and changes in medial cartilage volume and thickness reach 0.4 (16.7) %
      and 2.1 (11.3) %, respectively. Medial femoro-tibial joint space narrowing (JSN)
      after 1 year, assessed by radiography, was significantly correlated with a loss
      of medial tibial cartilage volume (r=0.25, P=0.046) and medial tibial cartilage
      thickness (r=0.28, P=0.025), over the same period. We found also a significant
      correlation between the progression of the WORMS and radiographic medial JSN over
      1 year (r=-0.35, P=0.006). All these results remained statistically significant
      after adjusting for age, sex and body mass index. CONCLUSION: This study shows a
      moderate but significant association between changes in JSW and changes in
      cartilage volume or thickness in knee joint of osteoarthritic patients.

PMID- 16890462
TI  - Kinectin participates in microtubule-dependent hormone secretion in pancreatic
      islet beta-cells.
AB  - Kinectin (KNT) is a candidate membrane receptor for kinesin in the movement of
      intracellular organelles along microtubules. Isoforms of KNT exist containing
      different combinations of six small (residues 23-33) variable domains (vd) vd1-6
      within the C-terminus. Here we investigate a role for KNT and its isoform KNTvd4(
      ) in the transport of amylin and insulin-containing secretory vesicles in the
      pancreatic islet beta-cell line RINm5F. KNTvd4(-) lacks vd4 that forms the
      kinesin-binding domain, and hence its role in the cell is an enigma. We report
      that amylin-containing vesicles also contained insulin, and exhibited
      microtubule, and small G-protein-dependent secretion. Knockdown of KNT by small
      interference RNA (siRNA) inhibited amylin expression and secretion. In contrast,
      recombinant KNTvd4(-) overexpressed in RINm5F cells associated with amylin
      containing vesicles and inhibited amylin secretion, but had no discernible affect
      on amylin expression. The data suggests that both KNT and KNTvd4(-) participate
      in microtubule-dependent secretion of amylin in islet beta-cells.

PMID- 16890463
TI  - Contrasting mechanisms of stem cell maintenance in Drosophila.
AB  - Stem cells are self-renewing multipotent cells essential for development or
      homeostasis of many tissues. Stem cell populations can be found in most
      multicellular plants and animals. The mechanisms by which these populations are
      maintained are diverse, utilizing both intrinsic and extrinsic factors to
      regulate cell division and differentiation. The genetic tools of the fruitfly,
      Drosophila melanogaster, have permitted detailed characterization of two stem
      cell populations. In this review, we will examine these contrasting stem cell
      model systems from Drosophila and their relevance to stem cell populations in
      other organisms.

PMID- 16890464
TI  - Steady-state free precession with hyperpolarized 3He: experiments and theory.
AB  - The magnetization response of hyperpolarized 3He gas to a steady-state free
      precession (SSFP) sequence was simulated using matrix product operators. The
      simulations included the effects of flip angle (alpha), sequence timings,
      resonant frequency, gas diffusion coefficient, imaging gradients, T1 and T2.
      Experiments performed at 1.5 T, on gas phantoms and with healthy human subjects,
      confirm the predicted theory, and indicate increased SNR with SSFP through use of
      higher flip angles when compared to optimized spoiled gradient echo (SPGR).
      Simulations and experiments show some compromise to the SNR and some point spread
      function broadening at high alpha due to the incomplete refocusing of transverse
      magnetization, caused by diffusion dephasing from the readout gradient. Mixing of
      gas polarization levels by diffusion between slices is also identified as a
      source of signal loss in SSFP at higher alpha through incomplete refocusing.
      Nevertheless, in the sample experiments, a SSFP sequence with an optimized flip
      angle of alpha=20 degrees, and 128 sequential phase encoding views, showed a
      higher SNR when compared to SPGR (alpha=7.2 degrees) with the same bandwidth.
      Some of the gas sample experiments demonstrated a transient signal response that
      deviates from theory in the initial phase. This was identified as being caused by
      radiation damping interactions between the large initial transverse magnetization
      and the high quality factor (Q=250) birdcage resonator. In 3He NMR experiments,
      performed without imaging gradients, diffusion dephasing can be mitigated, and
      the effective T2 is relatively long (1 s). Under these circumstances the SSFP
      sequence behaves like a CPMG sequence with sinalpha/2 weighting of SNR.
      Experiments and simulations were also performed to characterize the off-resonance
      behaviour of the SSFP HP 3He signal. Characteristic banding artifacts due to off
      resonance harmonic beating were observed in some of the in vivo SSFP images, for
      instance in axial slices close to the diaphragm where B0 inhomogeneity is
      highest. Despite these artifacts, a higher SNR was observed with SSFP in vivo
      when compared to the SPGR sequence. The trends predicted by theory of increasing
      SSFP SNR with increasing flip angle were observed in the range alpha=10-20
      degrees without compromise to image quality through blurring caused by excessive
      k-space filtering.

PMID- 16890465
TI  - Advances in asthma and COPD management: delivering CFC-free inhaled therapy using
      Modulite technology.
AB  - Inhaled corticosteroids (ICS) and long-acting beta-agonists (LABA) are currently
      used in the management of asthma and chronic obstructive pulmonary disease
      (COPD). Localized targeted delivery of these drugs into the lungs is achieved by
      means of two types of inhalation devices; pressurized metered-dose inhalers
      (pMDIs) and dry powder-inhalers (DPIs). For environmental reasons, the
      chlorofluorocarbon (CFC) propellants used in pMDIs are now being replaced by
      ozone friendly hydrofluoroalkanes (HFAs). These new generation HFA-based pMDIs,
      developed to provide effective lung deposition of the active moiety, have a
      favorable safety and tolerability profile. However, HFA-based re-formulation of
      LABAs and ICS for pMDIs presents particular technical difficulties, especially in
      terms of ensuring dose content uniformity. This review focuses on the technology
      and clinical efficacy of the HFA solution pMDIs using Modulite platform
      technology (Chiesi Farmaceutici S.p.A). Modulite technology allows the
      development of HFA solution formulations that can mimic the established CFC-based
      drug formulations on a microgram to microgram basis and provides formulations
      with novel particle size distributions that improve on existing delivery systems;
      by manipulation of aerosol clouds and particle size, the delivery of HFA
      formulated drugs can be optimized to either achieve fine particle fractions and
      deposition patterns similar to established CFC-based drug formulations, thus
      facilitating the transition to new environment-friendly pMDIs in the clinical
      setting, or achieve finer drug particles able to penetrate deeper into the
      bronchi for targeted drug delivery as medical need may dictate. Long-term,
      multiple-dose clinical studies of Modulite formulations of beclomethasone
      dipropionate (BDP), budesonide and formoterol have been demonstrated to be
      therapeutically equivalent to their respective previously established CFC or DPI
      formulations. As a result, a number of Modulite pMDIs have either recently gained
      regulatory approval in several European countries, or have completed clinical
      trials and are in the regulatory submission phase. Availability, in pMDI form, of
      drugs like formoterol, ICSs, and ICS/LABA combinations, all central to the
      effective management of asthma and COPD, is therefore expected to impact
      positively in assuring the continued availability of vital treatment options to
      patients and physicians.

PMID- 16890466
TI  - Increased expression of stress proteins in the surf clam Donax variabilis
      following hydrogen sulfide exposure.
AB  - Endogenous free radical production and resulting oxidative damage may result from
      exposure to hypoxia, hyperoxia, or hydrogen sulfide. Previous investigations of
      sulfide-induced oxidative damage have produced conflicting results, perhaps
      because these studies utilized species presumably adapted to sulfide. We examined
      the effects of sulfide, hypoxia and hyperoxia on the surf clam Donax variabilis
      to test whether these stressors induce a cellular response to oxidative stress.
      These clams inhabit high-energy sandy beaches and are unlikely to have specific
      adaptations to these stressors. In duplicate flow-through experiments performed
      in fall and spring, clams were exposed to normoxia (22 kPa P(O(2))), hypoxia (10
      kPa), hyperoxia (37 kPa), or sulfide with normoxia ( approximately 100 mumol L(
      1), 22 kPa respectively) for 24 h. We quantified whole-animal expression of three
      antioxidants (Cu/Zn and Mn superoxide dismutases, glutathione peroxidase), a
      lipid peroxidation marker (4-hydroxy-2E-nonenol-adducted protein), a DNA repair
      enzyme (OGG1-m), four heat shock proteins (small Hsp, Hsp60, Hsp70, and
      mitochondrial Hsp70), ubiquitin, and actin. Clams exposed to sulfide showed
      upregulation of the greatest number of stress proteins and the pattern was
      consistent with a cellular response to oxidative stress. Furthermore, there was a
      marked seasonality, with greater stress protein expression in clams from the
      spring.

PMID- 16890467
TI  - Environmental rearing conditions produce forebrain differences in wild Chinook
      salmon Oncorhynchus tshawytscha.
AB  - Recent studies suggest that hatchery-reared fish can have smaller brain-to-body
      size ratios than wild fish. It is unclear, however, whether these differences are
      due to artificial selection or instead reflect differences in rearing environment
      during development. Here we explore how rearing conditions influence the
      development of two forebrain structures, the olfactory bulb and the
      telencephalon, in juvenile Chinook salmon (Oncorhynchus tshawytscha) spawned from
      wild-caught adults. First, we compared the sizes of the olfactory bulb and
      telencephalon between salmon reared in a wild stream vs. a conventional hatchery.
      We next compared the sizes of forebrain structures between fish reared in an
      enriched NATURES hatchery and fish reared in a conventional hatchery. All fish
      were size-matched and from the same genetic cohort. We found that olfactory bulb
      and telencephalon volumes relative to body size were significantly larger in wild
      fish compared to hatchery-reared fish. However, we found no differences between
      fish reared in enriched and conventional hatchery treatments. Our results suggest
      that significant differences in the volume of the olfactory bulb and
      telencephalon between hatchery and wild-reared fish can occur within a single
      generation.

PMID- 16890468
TI  - Purification and characterization of milk clotting enzyme from goat (Capra
      hircus).
AB  - Chymosin, the major component of rennet (milk clotting enzyme), is an acid
      protease produced in the fourth stomach of milk-fed ruminants including goat and
      sheep in the form of an inactive precursor prochymosin. It is responsible for
      hydrolysis of kappa-casein chain in casein micelles of milk and therefore, used
      as milk coagulant in cheese preparation. The present investigation was undertaken
      to purify and characterize goat (Capra hircus) chymosin for its suitability as
      milk coagulant. The enzyme was extracted from abomasal tissue of kid and purified
      nearly 30-fold using anion exchanger and gel filtration chromatography. Goat
      chymosin resolved into three major active peaks, indicating possible
      heterogeneity when passed through DEAE-cellulose ion exchange column. The
      purified enzyme had a molecular mass of 36 kDa on SDS-PAGE, which was further
      confirmed by Western blot analysis. The purified enzyme preparation was stable up
      to 55 degrees C with maximum activity at 30 degrees C. The milk clotting activity
      was decreased steadily as pH is increased and indicated maximum activity at pH
      5.5. Proteolytic activity of goat chymosin increased with incubation time at 37
      degrees C. Goat chymosin was found to be more thermostable than cattle chymosin
      and equally stable to buffalo chymosin.

PMID- 16890469
TI  - Engineering a beta-carotene ketolase for astaxanthin production.
AB  - A new beta-carotene ketolase gene (crtW) was cloned from an environmental isolate
      Sphingomonas sp. DC18. A robust and reliable color screen was developed for
      protein engineering to improve its activity on hydroxylated carotenoids for
      astaxanthin production. Localized random mutagenesis was performed on the crtW
      gene including the upstream ribosomal binding site (RBS). Six mutations (H96L,
      R203W, A205V, A208V, F213L and A215T) in the crtW gene were isolated multiple
      times that showed improved astaxanthin production. These mutations were localized
      near the conserved histidine motifs, which were proposed for binding iron
      required for enzymatic activity. Combination of two of the mutations
      (R203W/F213L) further improved astaxanthin production. One mutation at the RBS
      (a438t) was shown to have additional effect on improving astaxanthin production.
      Most of the mutants still retained high activity on beta-carotene, however, the
      F213L single mutant and the R203W/F213L double mutant that yielded the highest
      improvement for astaxanthin production showed decreased activity for
      canthaxanthin production.

PMID- 16890470
TI  - Computational tools for isotopically instationary 13C labeling experiments under
      metabolic steady state conditions.
AB  - (13)C metabolic flux analysis (MFA) has become an important and powerful tool for
      the quantitative analysis of metabolic networks in the framework of metabolic
      engineering. Isotopically instationary (13)C MFA under metabolic stationary
      conditions is a promising refinement of classical stationary MFA. It accounts for
      the experimental requirements of non-steady-state cultures as well as for the
      shortening of the experimental duration. This contribution extends all
      computational methods developed for classical stationary (13)C MFA to the
      instationary situation by using high-performance computing methods. The developed
      tools allow for the simulation of instationary carbon labeling experiments
      (CLEs), sensitivity calculation with respect to unknown parameters, fitting of
      the model to the measured data, statistical identifiability analysis and an
      optimal experimental design facility. To explore the potential of the new
      approach all these tools are applied to the central metabolism of Escherichia
      coli. The achieved results are compared to the outcome of the stationary
      counterpart, especially focusing on statistical properties. This demonstrates the
      specific strengths of the instationary method. A new ranking method is proposed
      making both an a priori and an a posteriori design of the sampling times
      available. It will be shown that although still not all fluxes are identifiable,
      the quality of flux estimates can be strongly improved in the instationary case.
      Moreover, statements about the size of some immeasurable pool sizes can be made.

PMID- 16890471
TI  - [Image registration for radiation therapy: Practical aspects and quality
      control].
AB  - The development of conformal radiotherapy techniques (CRT) and intensity
      modulated CRT requires an accurate delineation of target structures and organs at
      risk. Thus, additional information provided by anatomical and/or functional
      imaging modalities can be used for volume of interest determination combined with
      traditionally used Computed Tomography imaging (CT): for instance, functional or
      morphological Magnetic Resonance Imaging (f MRI or m MRI) or Positron Emission
      Tomography (PET). A prerequisite to the simultaneous use of this information is
      image registration. Due to the differences between the images and the information
      they provide, a quality control of image registration process for radiotherapy is
      mandatory. The purpose of this article is to present the difficulties in
      implementing such controls and to show the necessity for a clinical validation on
      patient's images. The last part of this work presents the possible interest in
      using f MRI to help radio-oncologists in the treatment planning for gliomas
      associated to image coregistration and quality control considerations.

PMID- 16890472
TI  - [Maternal cannabis use and intra-uterine growth restriction].
AB  - Marijuana is the most commonly used illegal drug, especially among young women in
      Western societies. The effects of cannabis use during pregnancy have been studied
      for many years. The vast majority of studies have shown a link between maternal
      consumption of cannabis and foetal development. Foetal growth restriction seems
      to be the major complication of cannabis exposure. Nevertheless, all these
      studies have suffered from several methodological biases. The maternal marijuana
      use should be first and foremost detected in pregnant women for a specific
      addiction management and pregnancy follow-up.

PMID- 16890473
TI  - Model systems in ecology: dissecting the endophyte-grass literature.
AB  - Model systems can facilitate and focus research efforts but ill-chosen or inapt
      ones can distract or impede scientific progress. In this Opinion article, we pose
      the question: how can the literature provide appropriate general conclusions if
      the model systems upon which the literature is based are unrepresentative of the
      relevant biological diversity? A good example of this problem is the endophyte
      grass symbiosis, which is considered to be a classic example of mutualistic
      interactions. Meta-analysis of the primary literature demonstrates that the
      conceptual framework for endophyte-grass interactions has largely been based on
      endophyte-plant-herbivore studies of two agricultural grass species, tall fescue
      and perennial ryegrass. Consistent with conventional wisdom, the meta-analysis
      indicates that endophytes slightly increase grass resistance to herbivores. By
      contrast, endophytes appear not to affect plant performance or competitive
      ability. The positive effects of endophytes appear to be dependent on genetic
      variation in the host and endophyte, and on nutrient availability in soils. Thus,
      the agronomic grass model systems fail to capture the breadth of variability
      inherent in wild grass-endophyte populations and communities.

PMID- 16890475
TI  - A novel role for abscisic acid emerges from underground.
AB  - The continuous formation of lateral roots is a vital part of establishing a root
      system and enables plants to react with developmental plasticity to changing soil
      conditions. Evidence is accumulating that abscisic acid (ABA), which is known to
      be involved in stress responses, has an important role in lateral root formation.
      An ABA receptor mutant, fca-1, shows an altered response to ABA during lateral
      root formation. Interestingly, ABA seems to have distinct roles at different
      stages in lateral root development. The emerging role of ABA in lateral root
      development fits well with its general functional properties as a stress hormone,
      including its role in dormancy.

PMID- 16890474
TI  - Gamma-aminobutyrate: defense against invertebrate pests?
AB  - Gamma-aminobutyrate (GABA) is a ubiquitous four-carbon, non-protein amino acid.
      In plants, stress-induced GABA accumulation is well documented. However, the
      role(s) of GABA accumulation is contentious. In this Opinion article, we argue
      that wounding due to herbivory and crawling by insect larvae causes rapid GABA
      accumulation via the disruption of cellular compartmentation and the release of
      the acidic vacuolar contents to the cytosol. The activity of glutamate
      decarboxylase, the cytosolic enzyme responsible for GABA synthesis, has an acidic
      pH optimum. Subsequent GABA ingestion has a plant defense function by directly
      acting on GABA-regulated invertebrate neuromuscular junctions. Plants with an
      enhanced GABA-producing capacity reduce herbivory by invertebrate pests. These
      findings suggest that GABA accumulation is a rapidly deployed, local resistance
      mechanism that constitutes a first line of defense in deterring herbivory.

PMID- 16890476
TI  - Stomatal development: from neighborly to global communication.
AB  - Stomata are epidermal structures that are responsible for modulating the exchange
      of gases between the plant and the environment. Stomata are formed and patterned
      by asymmetric cell divisions. The number and orientation of these asymmetric
      divisions is informed by plant intrinsic signals acting locally (among epidermal
      cells) or at a distance (from mature to young leaves) and by plant extrinsic
      factors such as the quantity of light, water and CO(2) in the atmosphere. Recent
      studies have implicated a set of conserved cell surface receptors and
      intracellular signaling molecules in the perception and response to developmental
      cues. Complementary studies have probed the nature of environmental signals and
      how these signals are transduced from the site of perception to the cells in the
      stomatal lineage.

PMID- 16890477
TI  - Switching the flip: protein phosphatase roles in signaling pathways.
AB  - Protein phosphatases are the obligate partners of protein kinases in cellular
      control circuitry. Several specific roles of phosphatases have been revealed in
      plant systems through recent work capitalizing on functional genomics,
      interaction screens and activation-tagging approaches. Historically, the
      redundancy of genes that encode phosphatase functions has impeded genetic
      analysis in plant systems, and relatively few elucidated signaling pathways
      include protein phosphatases that have clearly defined substrates. Functional
      genomics, interaction and suppression screens, activation tagging and
      phosphoproteomics now hold great promise for identifying phosphatases that are
      active in signaling and regulation, and for revealing their in vivo substrates.
      This level of analysis will be essential for a full understanding of the effects
      of reversible protein phosphorylation in modulating and integrating cellular
      activities.

PMID- 16890478
TI  - C4' sugar oxidation of deoxyribonucleotide triphosphates by chromium(V)
      complexes.
AB  - The Cr(V) complexes, bis(2-ethyl-2-hydroxybutyrato)oxochromate(V)
      ([OCr(V)(ehba)(2)](-)) and (2,2-bis(hydroxymethyl)-2-(bis(2
      hydroxyethyl)amino)ethanolato)oxochromate(V) ([OCr(V)(BT)](2-)), were reacted
      with a series of deoxyribonucleotide triphosphates. Oxidation of deoxyribose at
      C4' was observed by measuring the amount of thiobarbituric acid reactive species
      (TBARS) produced in these reactions. For both compounds, the TBARS obtained with
      purine nucleotides was between 2.25 and 3.5 times greater than what was observed
      with pyrimidine nucleotide. This result suggests that the identity of the nucleic
      acid base can influence the hydrogen atom abstraction at C4'. Overall, the amount
      of product obtained with [OCr(V)(BT)](2-) was significantly less than what was
      observed with [OCr(V)(ehba)(2)](-), indicating that these two Cr(V) model
      complexes may oxidize DNA differently.

PMID- 16890480
TI  - Biphasic kinetics in the reaction between amino acids or glutathione and the
      chromium acetate cluster, [Cr3O(OAc)6]+.
AB  - Kinetics for the breakdown of the trinuclear chromium acetate cluster with a
      series of monoprotic and diprotic amino acid ligands and with glutathione in
      aqueous media have been investigated spectrophotometrically at pH 3.5-5.5 and in
      a temperature range of 45-60 degrees C. Under pseudo-first-order conditions,
      reactions with these ligands exhibited biphasic kinetic behavior that can be
      accounted for by a consecutive two-step reaction, A-->B-->C, where A is assumed
      to be a forced ion pair, B an intermediate and C is the product; experimental
      data fit to a biexponential equation for the transformation. Rates for k(short),
      k(long), and k(obs) were determined by manual extrapolation of absorbance data or
      curve-fitting routines; associated activation parameters for each step of the
      reaction were calculated using the Eyring equation. Rates for the first and
      second steps of the reaction are on the order of approximately 10(-4) and
      approximately 10(-5)s(-1), respectively. The large negative values of DeltaS++
      and smaller DeltaH++ in the first step indicate an associative step, while high
      positive values of DeltaS(double dagger) in the second step indicate
      dissociation. To account for the results mechanistically, the results are
      interpreted to be a first step of ligand exchange with a pseudo-axial aqua
      ligand, followed by a dissociative step involving acetate or oxo ligand
      displacement. The dissociative step is the rate determining step, with k(obs)
      approximately k(long). The results demonstrate reaction pathways that are
      available to the Cr(III) metal centers that may be physiologically relevant in
      the ligand-rich environment of biological systems. Under general conditions
      Cr(III) clusters may be expected to be broken down, unless some unique biological
      environment stabilizes the cluster. The present study has application to the
      processes related to Cr(III) transport and excretion, to potential mechanisms of
      Cr(III) action in a biological setting, and to the pharmacokinetics of Cr(III)
      supplements for animal and human consumption.

PMID- 16890481
TI  - Attention-deficit/hyperactivity disorder: use of cognitive evoked potential
      (P300) to predict treatment response.
AB  - OBJECTIVE: To evaluate the use of P300 in predicting treatment response to
      medicines in patients with Attention-Deficit/Hyperactivity Disorder (ADHD), and
      to confirm previous reports that 31-electrode mean auditory P300 amplitude (AA)
      predicts response to atomoxetine; and right fronto-central to parietal AA ratio
      predicts response to methylphenidate. METHODS: Efficacy and P300 data from 58
      children with ADHD enrolled in a double-blind crossover study using atomoxetine
      and methylphenidate were analyzed. Robust response was defined as 60% decrease
      from baseline in the ADHD rating scale. Response was alternately defined as
      greater than 50% decrease. RESULTS: Pre-treatment mean 31-electrode AA>6.8 microV
      predicted response to atomoxetine using both definitions of response. Right
      fronto-central to parietal AA ratio did not predict response to methylphenidate.
      A previous report that methylphenidate responders differed from non-responders in
      pre-treatment AA at T8 was confirmed, and AA at T8>7.65 microV predicted response
      to methylphenidate. 31-electrode mean P300 visual latency (VL) also predicted
      response to atomoxetine, as previously reported with imipramine. CONCLUSIONS:
      Mean AA predicts response to atomoxetine in ADHD patients. AA at T8 predicts
      response to methylphenidate. Such predictive tools may allow individually
      tailored choice of medicine in treatment of ADHD. SIGNIFICANCE: This allows a
      more informed decision of which medicine to use for a given patient.

PMID- 16890479
TI  - Incision of trivalent chromium [Cr(III)]-induced DNA damage by Bacillus
      caldotenax UvrABC endonuclease.
AB  - Some hexavalent chromium [Cr(VI)]-containing compounds are lung carcinogens. Once
      within cells, Cr(VI) is reduced to trivalent chromium [Cr(III)] which displays an
      affinity for both DNA bases and the phosphate backbone. A diverse array of
      genetic lesions is produced by Cr including Cr-DNA monoadducts, DNA interstrand
      crosslinks (ICLs), DNA-Cr-protein crosslinks (DPCs), abasic sites, DNA strand
      breaks and oxidized bases. Despite the large amount of information available on
      the genotoxicity of Cr, little is known regarding the molecular mechanisms
      involved in the removal of these lesions from damaged DNA. Recent work indicates
      that nucleotide excision repair (NER) is involved in the processing of Cr-DNA
      adducts in human and rodent cells. In order to better understand this process at
      the molecular level and begin to identify the Cr-DNA adducts processed by NER,
      the incision of CrCl(3) [Cr(III)]-damaged plasmid DNA was studied using a thermal
      resistant UvrABC NER endonuclease from Bacillus caldotenax (Bca). Treatment of
      plasmid DNA with Cr(III) (as CrCl(3)) increased DNA binding as a function of
      dose. For example, at a Cr(III) concentration of 1 microM we observed
      approximately 2 Cr(III)-DNA adducts per plasmid. At this same concentration of
      Cr(III) we found that approximately 17% of the plasmid DNA contained ICLs (
      approximately 0.2 ICLs/plasmid). When plasmid DNA treated with Cr(III) (1 microM)
      was incubated with Bca UvrABC we observed approximately 0.8 incisions/plasmid.
      The formation of endonuclease IV-sensitive abasic lesions or Fpg-sensitive
      oxidized DNA bases was not detected suggesting that the incision of Cr(III)
      damaged plasmid DNA by UvrABC was not related to the generation of oxidized DNA
      damage. Taken together, our data suggest that a sub-fraction of Cr(III)-DNA
      adducts is recognized and processed by the prokaryotic NER machinery and that
      ICLs are not necessarily the sole lesions generated by Cr(III) that are
      substrates for NER.

PMID- 16890482
TI  - Kinesthetic but not visual imagery assists in normalizing the CNV in Parkinson's
      disease.
AB  - OBJECTIVE: This study investigated whether kinesthetic and/or visual imagery
      could alter the contingent negative variation (CNV) for patients with Parkinson's
      disease (PD). METHODS: The CNV was recorded in six patients with PD and seven
      controls before and after a 10min block of imagery. There were two types of
      imagery employed: kinesthetic and visual, which were evaluated on separate days.
      RESULTS: The global field power (GFP) of the late CNV did not change after the
      visual imagery for either group, nor was there a significant difference between
      the groups. In contrast, kinesthetic imagery resulted in significant group
      differences pre-, versus post-imagery GFPs, which was not present prior to
      performing the kinesthetic imagery task. In patients with PD, the CNV amplitudes
      post-, relative to pre-kinesthetic imagery, increased over the dorsolateral
      prefrontal regions and decreased in the ipsilateral parietal regions. There were
      no such changes in controls. CONCLUSIONS: A 10-min session of kinesthetic imagery
      enhanced the GFP amplitude of the late CNV for patients but not for controls.
      SIGNIFICANCE: While the study needs to be replicated with a greater number of
      participants, the results suggest that kinesthetic imagery may be a promising
      tool for investigations into motor changes, and may potentially be employed
      therapeutically, in patients with Parkinson's disease.

PMID- 16890483
TI  - A comprehensive review of the effects of rTMS on motor cortical excitability and
      inhibition.
AB  - Repetitive transcranial magnetic stimulation (rTMS) procedures are being widely
      applied in therapeutic and investigative studies. Numerous studies have
      investigated the effects of rTMS on cortical excitability and inhibition,
      yielding somewhat contradictory results. The purpose of this study was to
      comprehensively review this literature to guide the selection of methodology in
      therapeutic studies. We conducted a comprehensive review of all identified
      studies that investigated effects of low and/or high frequency rTMS on motor
      cortical excitability or inhibition. Low frequency rTMS appears to produce a
      transient reduction in cortical excitability as assessed by motor evoked
      potential (MEP) size and produces no substantial effect on cortical inhibition.
      High frequency rTMS appears to produce a persistent increase in MEP size and a
      reduction in cortical inhibition measured with paired pulse methods although few
      studies have investigated frequencies greater than 5Hz. A number of novel
      stimulation paradigms have significant potential for altering cortical
      excitability but require further investigation. Although commonly applied forms
      of rTMS have effects on cortical excitability, more substantial effects may be
      obtained through the use of novel stimulation paradigms or innovative approaches
      to the stimulation of areas connected to a potential target site. Further
      research is required, however, before these paradigms can be more widely adopted.

PMID- 16890484
TI  - Pheochromocytoma induced cardiogenic shock with rapid recovery of ventricular
      function.
AB  - Pheochromocytoma is a rare cause of secondary hypertension. It may present
      atypically as cardiogenic shock with significant morbidity and mortality. We
      present a patient in cardiogenic shock dependent on an intra-aortic balloon pump
      and vasopressor support who completely recovered cardiac function within 96 h of
      hospitalization.

PMID- 16890485
TI  - Cardiomyocyte apoptosis is related to left ventricular dysfunction and
      remodelling in dilated cardiomyopathy, but is not affected by growth hormone
      treatment.
AB  - BACKGROUND AND AIMS: Cardiomyocyte apoptosis (CA) is a common feature of end
      stage heart failure. We examined whether CA is associated with cardiac
      dysfunction and remodelling in heart failure due to dilated cardiomyopathy and
      studied the effect of human growth hormone (hGH) on CA. METHODS AND RESULTS: We
      studied 38 patients, included in a phase III multi-center, randomised, double
      blind and placebo-controlled trial of biosynthetic hGH treatment in dilated
      cardiomyopathy, at baseline and after 14 weeks treatment. Twenty-six patients
      received hGH and 12 received placebo. CA was quantified in endomyocardial
      biopsies using the TUNEL assay. CA correlated with left ventricular size (r=0.43,
      p=0.007). Compared to patients with CA below the median of 0.53%, patients with
      CA above the median had significantly larger left ventricular volumes and lower
      ejection fractions (EF) by echocardiography (median (interquartile range)) 200 ml
      (84) vs. 257 ml (134) and 27% (11) vs. 23% (9). Expression of the Fas receptor
      was associated with a high rate of CA. hGH treatment significantly increased
      serum IGF-1 levels, but it had no effect on CA or cardiac structure and function.
      CONCLUSION: CA is related to left ventricular enlargement and dysfunction in
      dilated cardiomyopathy. CA is not affected by short-term treatment with hGH.

PMID- 16890486
TI  - Left bundle branch block as a risk factor for progression to heart failure.
AB  - The prevalence of conduction disturbances, particularly left bundle branch block
      (LBBB), is strongly correlated with age and with the presence of cardiovascular
      disease. LBBB has been reported to affect approximately 25% of the heart failure
      (HF) population and it is likely that the deleterious role of such conduction
      disorders in the progression to HF has been underestimated. The purpose of this
      article is to review the data from the literature indicating that LBBB may have a
      causative role, mediated through the resulting intra-ventricular asynchrony, in
      the deterioration of cardiac function and the development of cardiac remodelling
      and HF. It also aims to address the potential for future clinical therapies for
      this conduction disorder.

PMID- 16890487
TI  - Low prevalence of Chlamydia pneumoniae in adults with community-acquired
      pneumonia.
AB  - The incidence of community-acquired pneumonia (CAP) due to Chlamydia pneumoniae
      was determined in a prospective study of 546 adult patients with CAP included in
      the German CAP Competence Network (CAPNETZ) project. Three different PCR
      protocols for detection of C. pneumoniae in respiratory specimens were compared
      by a multicenter, inter-laboratory comparison involving three laboratories. A
      case was defined as a patient with a respiratory sample positive by PCR in at
      least two laboratories. CAP was caused by C. pneumoniae in 5/546 cases (0.9%).
      Antibody testing by microimmunofluorescence was done in 376 of 546 patients. All
      patients were negative for IgM antibodies. In the five PCR-positive patients,
      neither specific IgG nor IgA antibodies were found. Patients with CAP caused by
      C. pneumoniae had a lower median age (36 years) than the general study population
      (62 years). C. pneumoniae is currently a rare cause of CAP in adult patients in
      Germany. Analysis of a single serum sample is not useful for diagnosis of acute
      C. pneumoniae infection in CAP.

PMID- 16890488
TI  - The relationship between the VO2 slow component, muscle metabolites and
      performance during very-heavy exhaustive exercise.
AB  - This study examined the relationship between the V O(2) response, particularly
      the slow component (SC), muscle metabolite changes and performance during very
      heavy exhaustive exercise. Sixteen active females performed a graded exercise
      test to determine V O(2peak) and the lactate threshold followed 48h later by a
      constant-load cycle test to exhaustion (ET) at 85% V O(2peak) intensity. Muscle
      biopsies and capillary blood samples were obtained before and after the ET to
      determine changes in muscle ATP, pH, lactate and phosphocreatine and also plasma
      pH and lactate. Breath-by-breath data from the ET were smoothed using 5-s
      averages and fit to a three-component exponential model. The mean time to
      exhaustion (t(exh)) during the ET was 16.8 (+/-6.4) min. Results showed no
      correlation between the SC and t(exh) or any muscle metabolite changes (p>0.05).
      Significant correlations (p<0.05) were evident between t(exh) and tau; tau(0) (r=
      0.54), tau(1) (r=-0.65), change in (Delta) pH(b) (r=-0.60), Delta[La(-)](b) (r=
      0.58) and [La(-)](b post) (r=-0.64). Significant correlations (p<0.05) were also
      evident between tau(1) and [La(-)](b post) (r=0.54). Furthermore, a negative
      value resulted when the accumulated oxygen deficit was calculated for the entire
      duration of the ET. Results showed no association between the amplitude of the SC
      and t(ext) or to changes in muscle/blood metabolites, suggesting that the SC is
      not a determinant of high-intensity exercise tolerance. Furthermore, it is
      possible that a reduced perturbation of anaerobic energy sources, as a result of
      a faster tau(1), may have contributed to a longer t(exh).

PMID- 16890489
TI  - Dissemination of a community-based physical activity project: the case of 10,000
      steps.
AB  - This paper describes the use of a web-site for the dissemination of the community
      based '10,000 steps' program which was originally developed and evaluated in
      Rockhampton, Queensland in 2001-2003. The website provides information and
      interactive activities for individuals, and promotes resources and programs for
      health promotion professionals. The dissemination activity was assessed in terms
      of program adoption and implementation. In a 2-year period (May 2004-March 2006)
      more than 18,000 people registered as users of the web-site (logging more than
      8.5 billion steps) and almost 100 workplaces and 13 communities implemented
      aspects of the 10,000 steps program. These data support the use of the internet
      as an effective means of disseminating ideas and resources beyond the
      geographical borders of the original project. Following this preliminary
      dissemination, there remains a need for the systematic study of different
      dissemination strategies, so that evidence-based physical activity programs can
      be translated into more widespread public health practice.

PMID- 16890491
TI  - Impaired innate immunity in Crohn's disease.
AB  - The aetiology of Crohn's disease--a chronic intestinal disorder that involves an
      immune response against the commensal bacterial flora--remains fiercely debated.
      Two hypotheses exist: (i) those who think that the disease is caused by genetic
      defects that produce exaggerated innate responses to the flora, leading to
      excessive inflammation; and (ii) those who think that the genetic defects cause
      diminished inflammatory responses, in turn leading to uncontrolled accumulation
      of the inducer stimuli and, thus, activation of the adaptive immune system.
      Importantly, Marks and colleagues have recently investigated the immune response
      of Crohn's disease patients directly, convincingly showing impaired innate
      immunity.

PMID- 16890490
TI  - Towards a molecular understanding of human diseases using Dictyostelium
      discoideum.
AB  - The social amoeba Dictyostelium discoideum is increasingly being used as a simple
      model for the investigation of problems that are relevant to human health. This
      article focuses on several recent examples of Dictyostelium-based biomedical
      research, including the analysis of immune-cell disease and chemotaxis,
      centrosomal abnormalities and lissencephaly, bacterial intracellular
      pathogenesis, and mechanisms of neuroprotective and anti-cancer drug action. The
      combination of cellular, genetic and molecular biology techniques that are
      available in Dictyostelium often makes the analysis of these problems more
      amenable to study in this system than in mammalian cell culture. Findings that
      have been made in these areas using Dictyostelium have driven research in
      mammalian systems and have established Dictyostelium as a powerful model for
      human-disease analysis.

PMID- 16890492
TI  - Estrogen receptors: new players in diabetes mellitus.
AB  - Diabetes mellitus type 2 is a systemic disease characterized by imbalance of
      energy metabolism, which is mainly caused by inadequate insulin action. Recent
      data have revealed a surprising role for estradiol in regulating energy
      metabolism and opened new insights into the role of the two estrogen receptors,
      ERalpha and ERbeta, in this context. New findings on gene modulation by ERalpha
      and ERbeta of insulin-sensitive tissues indicate that estradiol participates in
      glucose homeostasis by modulating the expression of genes that are involved in
      insulin sensitivity and glucose uptake. Drugs that can selectively modulate the
      activity of either ERalpha or ERbeta in their interactions with target genes
      represent a promising frontier in diabetes mellitus coadjuvant therapy.

PMID- 16890493
TI  - Model of stimulation-responsive splicing and strategies in identification of
      immunogenic isoforms of tumor antigens and autoantigens.
AB  - We recently proposed a novel model of stimulation-responsive splicing for the
      selection of autoantigens and self-tumor antigens. Our model theorizes that the
      significantly higher rates of alternative splicing of autoantigen and self-tumor
      antigen transcripts that occur in response to stimuli could induce extra-thymic
      expression of untolerized antigen epitopes for elicitation of autoimmune and anti
      tumor responses. To facilitate the identification of immunogenic isoforms of
      antigens, we have developed strategies using improved SEREX in conjunction with
      database-mining and immunogenic isoform mapping. Identification of immunogenic
      isoforms of autoantigens and self-tumor antigens is very important for the
      development of novel therapeutics and diagnostic tools for autoimmune diseases
      and tumors, such as: (1) autoantigen isoform microarrays for disease diagnosis
      and prognosis; (2) autoantigen isoform-specific tolerizing vaccines and splicing
      redirection therapies, as well as (3) immunogenic antigen isoform-specific
      immunotherapy for tumors.

PMID- 16890494
TI  - Women's health in developing countries.
AB  - Healthcare priorities are different in developing and developed countries. A more
      effective resource allocation, complemented by efforts to implement only those
      practices that are effective, should be a priority for improving reproductive
      health services in developing countries. A large burden of gynaecological disease
      exists in developing countries and it is difficult to envisage serious reforms
      and improvements without an increase in public-sector spending. However,
      communities themselves could assume some responsibility for women's health in
      ways that prioritize women's own perceptions and primary needs. In this chapter
      we have compiled existing evidence regarding various gynaecological problems
      faced by women in developing countries. To name a few: sexual health issues,
      abortion, subfertility, cancer, and genital fistulae. We believe that there is a
      large knowledge gap in the area of women's health in developing countries, and
      there is an urgent need to conduct appropriately designed studies.

PMID- 16890495
TI  - Language dominance in mesial temporal lobe epilepsy: a functional transcranial
      Doppler sonography study of brain plasticity.
AB  - Functional transcranial Doppler sonography was used to study hemispheric language
      dominance (HLD) in 24 right-handed patients with left temporal lobe epilepsy
      (TLE) and a structural lesion in the left temporal lobe and in 69 healthy
      controls. Twenty-five percent of the patients and 4% of controls showed atypical
      (right or bilateral) HLD. Degree of HLD was not correlated with age, Full Scale
      IQ, Verbal IQ, spike frequency, seizure frequency, age at seizure onset, or
      duration of TLE. Atypical HLD appears to be lesion-induced, independent of
      epilepsy characteristics.

PMID- 16890496
TI  - Effect of aerial exposure on the antioxidant status in the subantarctic stone
      crab Paralomis granulosa (Decapoda: Anomura).
AB  - In Tierra del Fuego (Southern South America), the stone or false king crab,
      Paralomis granulosa represents one of the most important crab fisheries. After
      capture, animals are kept in baskets and exposed to dryness for several hours,
      when the water flow through the gills is interrupted. As a consequence a
      concomitant increase of reactive oxygen species begins, triggering oxidative
      stress. The aim of this study was to determine oxidative stress and antioxidant
      enzyme activities due to air exposure in different tissues of P. granulosa. Fifty
      crabs (carapace length >82 mm) were captured in Beagle Channel (54 degrees 50'S,
      68 degrees 20'W) during winter 2004. Five groups of 10 crabs each were exposed to
      dryness at 6 degrees C for 0, 3, 6, 12 or 24 h, respectively. Activity of
      superoxide dismutase (SOD), catalase (CAT), glutathione S transferase (GST)
      protein and lipid oxidation were measured in gills, muscle, hepatopancreas and
      haemolymph samples. Almost all analyzed tissues showed antioxidant enzymes
      activity, which varied with time of air exposure. The maximum enzyme activity was
      measured after 6 h of air exposure. Protein oxidation levels varied significantly
      in gills. Lipid peroxidation levels increased significantly in muscle and
      hepatopancreas. The critical time of air exposure probably occurs at 6 h.
      Thereafter animals were unable to induce the synthesis of antioxidant enzymes or
      proteins. This should be taken into account to minimize the stress generated by
      the commercial capture process.

PMID- 16890497
TI  - Leptin inhibits cell growth of human vascular smooth muscle cells.
AB  - Elevated leptin levels are thought to contribute to the individual cardiovascular
      risk, however, the role of leptin in the pathogenesis of atherosclerosis remains
      unclear. The aim of our study was to elucidate the effects of leptin on growth of
      human vascular smooth muscle cells (VSMC) and leptin receptor expression. By
      establishing a new quantitative real-time PCR for leptin receptor (ObR) isoforms
      we showed that the short isoforms of ObR were expressed in a 10- to 27-fold
      excess compared to the long isoform in cultured human VSMCs. Incubation of VSMCs
      with 100 ng/ml leptin downregulated the short isoforms significantly, whereas the
      long isoform was not influenced. Increasing leptin concentrations of 50 and 100
      ng/ml significantly reduced the cell number of VSMCs compared to untreated
      controls. Our findings suggest a role for leptin in vascular smooth muscle cell
      growth, associated to a downregulation of leptin receptor isoforms.

PMID- 16890498
TI  - Correlations between treatment outcome and both anti-MSP119 antibody response and
      erythrocyte-related genetic factors in Plasmodium falciparum malaria.
AB  - Treatment efficacy is related to the interaction of three parameters: drug,
      parasites, and human factors. The role of human factors in treatment outcome has
      been poorly documented to date, although human genetic factors and specific
      immunity have been related to protection against malaria. This study aimed to
      evaluate a possible cooperation between drug efficacy and host factors in
      treatment success. The contribution of host factors to treatment efficacy was
      studied in Gabonese children with a non-severe malaria attack. Children (n=232)
      aged under 10 years were treated with either sulfadoxine-pyrimethamine or
      amodiaquine. The influence of erythrocyte-related genetic factors and humoral
      immune responses (IgG and subclasses) against MSP1(19) on anti-malarial treatment
      outcome during a 28-day follow-up was studied. Sickle-cell trait carriage and
      anti-MSP1(19) IgG3 levels were related to lower parasite densities at enrolment
      (multiple linear regression analysis, P<or=0.005). Strikingly, early failures
      after AQ or SP treatment were associated with decreased anti-MSP1(19) IgG, IgG1
      and IgG3 levels at enrolment. However, this finding was achieved in a low number
      of children presenting with an early failure. Kinetics of anti-MSP1(19) IgG and
      subclasses between Days 0 and 28 were also related to treatment efficacy, as the
      most effective treatment (sulfadoxine-pyrimethamine) was characterised by a
      higher elevation of antibody titres by Day 28. No effect of erythrocyte-related
      genetic factors on treatment outcome was shown, although the protective role of
      sickle-cell trait against higher parasitaemias was confirmed at enrolment. Our
      data suggest that anti-MSP1(19) IgG1 may have a supportive role during the first
      days of treatment to prevent early failures. The interference between drug
      efficacy, immunity and human genetic factors needs further investigation to be
      elucidated.

PMID- 16890499
TI  - The tsetse fly Glossina palpalis palpalis is composed of several genetically
      differentiated small populations in the sleeping sickness focus of Bonon, Cote
      d'Ivoire.
AB  - Glossina palpalis is the main vector of human African trypanosomosis (HAT, or
      sleeping sickness) that dramatically affects human health in sub-Saharan Africa.
      Because of the implications of genetic structuring of vector populations for the
      design and efficacy of control campaigns, G. palpalis palpalis in the most active
      focus of sleeping sickness in Cote d'Ivoire was studied to determine whether this
      taxon is genetically structured. High and statistically significant levels of
      within population heterozygote deficiencies were found at each of the five
      microsatellite loci in two temporally separated samples. Neither null alleles,
      short allele dominance, nor trap locations could fully explain these deviations
      from random mating, but a clustering within each of the two samples into
      different genetic sub-populations (Wahlund effect) was strongly suggested. These
      different genetic groups, which could display differences in infection rates and
      trypanosome identity, were composed of small numbers of individuals that were
      captured together, leading to the observed Wahlund effect. Implications of this
      population structure on tsetse control are discussed.

PMID- 16890500
TI  - Absence of DNA polymerase theta results in decreased somatic hypermutation
      frequency and altered mutation patterns in Ig genes.
AB  - Multiple DNA polymerases participate in somatic hypermutation of immunoglobulin
      (Ig) genes. Mutations at A/T are largely dependent on DNA polymerase eta (POLH)
      whereas mutations at C/G appear to be generated by several DNA polymerases. We
      have previously shown that mice expressing a catalytically inactive POLQ (Polq
      inactive) have a reduction in C/G mutations. Here we have generated mice that
      completely lack Polq expression (Polq-null). Polq-null mice have no obvious
      abnormality in B or T cell differentiation, and their splenic B cells responded
      normally to various activation signals and underwent normal Ig gene class
      switching. The mutant mice mounted relatively normal immune responses against a T
      dependent antigen although there was a slight decrease in antigen specific
      antibodies. Polq-null mice exhibited a mild reduction in the overall mutation
      frequency, however, in contrast to Polq-inactive mice where the reduction mostly
      affected mutations at C/G, Polq-null mice showed a reduction of both C/G and A/T
      mutations and there was a significant increase of G to C transversions. These
      results confirm a role for POLQ in somatic hypermutation and suggest that in the
      complete absence of POLQ other polymerases may functionally substitute, resulting
      in a mutation pattern different from that found in Polq-inactive mice.

PMID- 16890501
TI  - Quantitative determination of nystatin in human plasma using LC-MS after
      inhalative administration in healthy subjects.
AB  - The antifungal polyene antibiotics nystatin was tested in a clinical trial to
      describe pharmacokinetics and safety after repeated administration of Nystatin
      "Lederle" sterile powder in healthy volunteers. To monitor the nystatin
      concentration-time profile in plasma we developed a sensitive method in the range
      of 1-100ng/ml based on liquid chromatography coupled with tandem mass
      spectrometry. The target substance was separated from the biological matrix on
      C(18) solid-phase extraction cartridges with methanol. The Chromatography was
      performed isocratically using a reversed phase Caltrex Resorcinearene column. The
      mobile phase consisted of 5mM ammonium formate buffer and acetonitrile (40:60,
      v/v). The mass spectrometer works with electrospray ionization in its positive
      selected ion monitoring (SIM) mode using the respective MH(+) ions, m/z 926.6 for
      nystatin and m/z 924.4 for amphotericin B as internal standard. The method
      validation was performed according to the demands and international criteria for
      validation of bioanalytical methods and was successfully applied to the
      quantification of nystatin in human plasma in the pharmacokinetic trial.

PMID- 16890502
TI  - Potential of a simple solid-phase extraction method coupled to analytical and
      bioanalytical methods for an improved determination of microcystins in algal
      samples.
AB  - Artemia assays and protein phosphatase assays are commonly used for the screening
      of microcystins (MCs) in algal samples instead of the standard mouse toxicity
      assay. However, it has been shown that their results are often biased because of
      the matrix effects. To eliminate the possible interferences in the algal
      matrices, a new solid-phase extraction (SPE) method using silica gel as a sorbent
      was developed and evaluated. Results show that this SPE method could not only
      reduce the toxicity of the Microcystis samples towards brine shrimp by 50-80% but
      also eliminate 90-100% of the endogenous phosphatase activity from Spirulina and
      Chlorella samples, thus improving the determination of microcystins in algal
      samples using either of the two bioanalytical methods. The application of this
      SPE method as an off-line cleanup for high-performance liquid chromatography
      (HPLC) with UV detection is also described in this study. After SPE, the HPLC
      chromatograms of Microcystis samples have clear baselines that have no
      interferences with the analyte peaks.

PMID- 16890503
TI  - Determination of d-serine and related neuroactive amino acids in human plasma by
      high-performance liquid chromatography with fluorimetric detection.
AB  - A simple and versatile methodology using high-performance liquid chromatography
      (HPLC) with fluorimetric detection was developed to simultaneously determine d
      serine along with other metabolically related neuroactive amino acids in the
      glutamatergic system: L-serine, L-glutamate, L-glutamine, and glycine. On-column
      sensitivity was in the lower picomole range. Of two chiral thiol reagents
      investigated, amino acid derivatives of o-phthaldialdehyde (OPA) in combination
      with N-isobutyryl-L-cysteine were found to have consistently higher responses
      than their corresponding N-tert-butyloxycarbonyl-L-cysteine derivatives. This
      methodology was applied to the quantitative detection of amino acids in human
      plasma and lays the foundation for further investigations of the role of
      neuroactive amino acids in the pathophysiology and treatment of neurological and
      psychiatric disorders.

PMID- 16890504
TI  - Determination of acteoside in Cistanche deserticola and Boschniakia rossica and
      its pharmacokinetics in freely-moving rats using LC-MS/MS.
AB  - A sensitive LC-MS/MS method with a simple solid-phase extraction for the
      determination of acteoside in rat plasma and tissue homogenates was established
      for the investigation of bioavailability and brain distribution in freely-moving
      rats. Acteoside in Cistanche deserticola and Boschniakia rossica was also
      determined. Acteoside and internal standard were separated on a RP-select B
      column (125mmx4.6mm i.d., particle size 5microm). The mobile phase consisted of
      35% methanol and 65% acetic acid-water (1:100, v/v) at a flow-rate of 1mL/min.
      Acteoside and the internal standard were monitored using the multiple-reaction
      monitoring (MRM) mode at m/z transitions of 623-->161 and 609-->301,
      respectively. The acteoside content was 38.4+/-2.4mg/kg (n=3) for B. rossica,
      which is obviously lower than 21134.2+/-805.5mg/kg (n=3) of C. deserticola. The
      protein binding in rat plasma was 75.5+/-1.8%. The brain distribution result
      indicated that acteoside was evenly distributed in brain tissues (brain stem,
      cerebellum, the rest of the brain, cortex, hippocampus and striatum) which was
      about 0.45-0.68% of that in plasma (4.5+/-0.5microg/mL) after 15min of acteoside
      administration (10mg/kg, i.v.). After acteoside was given (3mg/kg, i.v.;
      100mg/kg, p.o.), the oral bioavailability
      (AUC(p.o.)/dose(p.o.))/(AUC(i.v.)/dose(i.v.)) was only 0.12%.

PMID- 16890505
TI  - Dried plum prevents bone loss in a male osteoporosis model via IGF-I and the RANK
      pathway.
AB  - Previously, dietary supplementation with dried plums, a rich source of
      polyphenolic compounds with antioxidant and anti-inflammatory properties, has
      been shown to improve bone density, microstructure and biomechanics in female
      animal models of osteopenia. We designed this study to determine the extent to
      which dried plum prevents skeletal deterioration in gonadal hormone deficient
      male animals and to begin to understand its mechanism of action. Sixty 6-month
      old male Sprague-Dawley rats were either sham-operated (Sham = 1 group) or
      orchidectomized (ORX = 4 groups) and randomly assigned to dietary treatments:
      standard semi-purified diet (Control) with either LD = 5%, MD = 15%, or HD = 25%
      (w/w) dried plum for 90 days. At the end of the treatment period, both the MD and
      HD dried plum completely prevented the ORX-induced decrease in whole body, femur,
      and lumbar vertebra bone mineral density (BMD). Biomechanical testing indicated
      that the MD and HD of dried plum prevented the ORX-induced decrease in ultimate
      load of the cortical bone as well as the compressive force and stiffness of
      trabecular bone within the vertebrae. Analyses of trabecular microarchitecture of
      the distal femur metaphysis and vertebral body revealed that HD dried plum
      protected against the decrease in trabecular bone volume (BV/TV) induced by ORX.
      In the distal femur, all doses of dried plum improved trabecular number (TbN) and
      separation (TbSp) compared to the ORX-control group, while MD and HD dried plum
      prevented the ORX-induced changes in vertebral TbN and TbSp. At the end of the 90
      day treatment, no remarkable changes in serum osteocalcin or alkaline phosphatase
      in any of the treatment groups were observed, while serum insulin-like growth
      factor (IGF)-I was increased by dried plum. The ORX-induced increase in urinary
      deoxypyridinoline (DPD) excretion was completely prevented by all doses of dried
      plum coinciding with down-regulation of gene expression for receptor activator of
      NFkappa-B ligand (RANKL) and osteoprotegerin (OPG) in the bone. We conclude that
      dried plum prevents osteopenia in androgen deficient male rats, and these
      beneficial effects may be attributed in part to a decrease in osteoclastogenesis
      via down-regulation of RANKL and stimulation of bone formation mediated by IGF-I.

PMID- 16890506
TI  - Re: "The effects of local platelet rich plasma delivery on diabetic fracture
      healing". What do we use: Platelet-rich plasma or platelet-rich gel?

PMID- 16890507
TI  - Macaques.

PMID- 16890508
TI  - Communication in ants.

PMID- 16890509
TI  - Broad taxon and gene sampling indicate that chaetognaths are protostomes.

PMID- 16890511
TI  - Near-human aneuploidy levels in female mice with homeologous chromosomes.

PMID- 16890510
TI  - Chaetognath phylogenomics: a protostome with deuterostome-like development.

PMID- 16890512
TI  - Vision: stimulating your attention.
AB  - Attentional selection biases the processing of higher visual areas to particular
      parts of a scene. Recent experiments show how stimulation of neurons in the
      frontal eye fields can mimic this process.

PMID- 16890513
TI  - Engineered crops: transgenes go wild.
AB  - Genetically modified Agrostis stolonifera has escaped from cultivation. For the
      first time, a herbicide-resistant perennial weed has established itself in wild
      populations.

PMID- 16890514
TI  - Neural coding: hybrid analog and digital signalling in axons.
AB  - Mammalian axons are thought to act as digital signaling devices, conveying
      information only by the timing and rate of all-or-none action potentials. Two
      recent studies now show that synaptic potentials can also spread far down the
      axon and influence action potential-triggered transmitter release in a graded,
      'analog' manner. Axons thus encode information both about subthreshold and
      suprathreshold synaptic activity.

PMID- 16890515
TI  - IKK epsilon signaling: not just NF-kappaB.
AB  - IkappaB kinases (IKKs) are key components of NF-kappaB signaling pathways in
      innate immunity and inflammation. Surprisingly, three recent reports implicate
      IKKs in Drosophila in seemingly unrelated functions, including non-apoptotic
      caspase activation and cytoskeleton organization.

PMID- 16890516
TI  - Neuroeconomics: cardinal utility in the orbitofrontal cortex?
AB  - Modern economics no longer uses the concept of cardinal utility, which describes
      the value of a good independently of a comparison with another good. New
      electrophysiological recordings in primates performing economic choices suggest a
      neurological substrate for cardinal utility, a finding that economists should
      perhaps take note of.

PMID- 16890517
TI  - Phylogeny: the continuing classificatory conundrum of chaetognaths.
AB  - The phylogenetic conundrum posed by the Chaetognatha, a cryptic phylum consisting
      largely of planktonic predators, is the subject of two short papers in this issue
      of Current Biology. These analyses go some way towards defining the phylogenetic
      position of the chaetognaths, which possess features apparently spanning the
      protostome/deuterostome divide.

PMID- 16890518
TI  - Declarative memory: sleep protects new memories from interference.
AB  - Interference is one of the most fundamental phenomena in memory research:
      acquiring new memories causes forgetting of other, related memories. A new study
      shows that sleep, interposed between learning episodes, can mitigate the extent
      to which new (post-sleep) learning interferes with recall of previously acquired
      knowledge.

PMID- 16890519
TI  - Animal communication: do dolphins have names?
AB  - A new study of contact calls in dolphins shows that individuals can recognize one
      another using information encoded in the frequency modulation pattern of these
      calls, in the absence of general voice characteristics.

PMID- 16890520
TI  - Social evolution: lazy wasps look to the future.
AB  - Female hairy-faced hover wasps forage for the young of a dominant breeder, but
      some forage more than others. New research shows that helpers decide how much to
      help by looking to the future.

PMID- 16890521
TI  - Animal memory: episodic-like memory in rats.
AB  - Recent experiments with rats on a radial maze indicate that they can remember
      what foods they encountered, and when and where they encountered them. These
      findings, and others with food-storing birds, challenge the idea that only humans
      have episodic memory.

PMID- 16890522
TI  - Cilia: tuning in to the cell's antenna.
AB  - Cilia are microtubule-based organelles that project like antennae from the
      surface of most cells in the body. Motile cilia move fluid past cells, for
      example mucus in the airway. Non-motile primary cilia, however, transduce a
      multitude of sensory stimuli, including chemical concentrations of growth
      factors, hormones, odorants, and developmental morphogens, as well as osmolarity,
      light intensity, and fluid flow. Cilia have evolved a complex ultrastructure to
      accommodate these diverse functions, and an extensive molecular machinery has
      developed to support the assembly of these organelles. Defects in the cilia
      themselves, or the machinery required to assemble them, lead to a broad spectrum
      of human disease symptoms, including polycystic kidney disease, nephronophthisis,
      hydrocephalus, polydactyly, situs inversus, retinal degeneration, and obesity.
      While these diseases highlight the pivotal roles of cilia in physiology and
      development, the mechanistic link between cilia, physiology, and disease remains
      unclear.

PMID- 16890523
TI  - Concurrent TMS-fMRI and psychophysics reveal frontal influences on human
      retinotopic visual cortex.
AB  - BACKGROUND: Regions in human frontal cortex may have modulatory top-down
      influences on retinotopic visual cortex, but to date neuroimaging methods have
      only been able to provide indirect evidence for such functional interactions
      between remote but interconnected brain regions. Here we combined transcranial
      magnetic stimulation (TMS) with concurrent functional magnetic resonance imaging
      (fMRI), plus psychophysics, to show that stimulation of the right human frontal
      eye-field (FEF) produced a characteristic topographic pattern of activity changes
      in retinotopic visual areas V1-V4, with functional consequences for visual
      perception. RESULTS: FEF TMS led to activity increases for retinotopic
      representations of the peripheral visual field, but to activity decreases for the
      central field, in areas V1-V4. These frontal influences on visual cortex occurred
      in a top-down manner, independently of visual input. TMS of a control site
      (vertex) did not elicit such visual modulations, and saccades, blinks, or pupil
      dilation could not account for our results. Finally, the effects of FEF TMS on
      activity in retinotopic visual cortex led to a behavioral prediction that we
      confirmed psychophysically by showing that TMS of the frontal site (again
      compared with vertex) enhanced perceived contrast for peripheral relative to
      central visual stimuli. CONCLUSIONS: Our results provide causal evidence that
      circuits originating in the human FEF can modulate activity in retinotopic visual
      cortex, in a manner that differentiates the central and peripheral visual field,
      with functional consequences for perception. More generally, our study
      illustrates how the new approach of concurrent TMS-fMRI can now reveal causal
      interactions between remote but interconnected areas of the human brain.

PMID- 16890525
TI  - Control of cardiac rhythm by ORK1, a Drosophila two-pore domain potassium
      channel.
AB  - Unravelling the mechanisms controlling cardiac automatism is critical to our
      comprehension of heart development and cardiac physiopathology. Despite the
      extensive characterization of the ionic currents at work in cardiac pacemakers,
      the precise mechanisms initiating spontaneous rhythmic activity and,
      particularly, those responsible for the specific control of the pacemaker
      frequency are still matters of debate and have not been entirely elucidated. By
      using Drosophila as a model animal to analyze automatic cardiac activity, we have
      investigated the function of a K+ channel, ORK1 (outwardly rectifying K+ channel
      1) in cardiac automatic activity. ORK1 is a two-pore domain K+ (K2P) channel,
      which belongs to a diverse and highly regulated superfamily of potassium
      selective leak channels thought to provide baseline regulation of membrane
      excitability. Cardiac-specific inactivation of Ork1 led to an increase in heart
      rhythm. By contrast, when overexpressed, ORK1 completely prevented heart beating.
      In addition, by recording action potentials, we showed that the level of Ork1
      activity sets the cardiac rhythm by controlling the duration of the slow
      diastolic depolarization phase. Our observations identify a new mechanism for
      cardiac rhythm control and provide the first demonstration that K2P channels
      regulate the automatic cardiac activity.

PMID- 16890524
TI  - Mps1 phosphorylation of Dam1 couples kinetochores to microtubule plus ends at
      metaphase.
AB  - BACKGROUND: Duplicated chromosomes are equally segregated to daughter cells by a
      bipolar mitotic spindle during cell division. By metaphase, sister chromatids are
      coupled to microtubule (MT) plus ends from opposite poles of the bipolar spindle
      via kinetochores. Here we describe a phosphorylation event that promotes the
      coupling of kinetochores to microtubule plus ends. RESULTS: Dam1 is a kinetochore
      component that directly binds to microtubules. We identified DAM1-765, a dominant
      allele of DAM1, in a genetic screen for mutations that increase stress on the
      spindle pole body (SPB) in Saccharomyces cerevisiae. DAM1-765 contains the single
      mutation S221F. We show that S221 is one of six Dam1 serines (S13, S49, S217,
      S218, S221, and S232) phosphorylated by Mps1 in vitro. In cells with single
      mutations S221F, S218A, or S221A, kinetochores in the metaphase spindle form
      tight clusters that are closer to the SPBs than in a wild-type cell. Five lines
      of experimental evidence, including localization of spindle components by
      fluorescence microscopy, measurement of microtubule dynamics by fluorescence
      redistribution after photobleaching, and reconstructions of three-dimensional
      structure by electron tomography, combined with computational modeling of
      microtubule behavior strongly indicate that, unlike wild-type kinetochores, Dam1
      765 kinetochores do not colocalize with an equal number of plus ends. Despite the
      uncoupling of the kinetochores from the plus ends of MTs, the DAM1-765 cells are
      viable, complete the cell cycle with the same kinetics as wild-type cells, and
      biorient their chromosomes as efficiently as wild-type cells. CONCLUSIONS: We
      conclude that phosphorylation of Dam1 residues S218 and S221 by Mps1 is required
      for efficient coupling of kinetochores to MT plus ends. We find that efficient
      plus-end coupling is not required for (1) maintenance of chromosome
      biorientation, (2) maintenance of tension between sister kinetochores, or (3)
      chromosome segregation.

PMID- 16890526
TI  - Resolving head rotation for human bipedalism.
AB  - Alignment of the body to the gravitational vertical is considered to be the key
      to human bipedalism. However, changes to the semicircular canals during human
      evolution suggest that the sense of head rotation that they provide is important
      for modern human bipedal locomotion. When walking, the canals signal a mix of
      head rotations associated with path turns, balance perturbations, and other body
      movements. It is uncertain how the brain uses this information. Here, we show
      dual roles for the semicircular canals in balance control and navigation control.
      We electrically evoke a head-fixed virtual rotation signal from semicircular
      canal nerves as subjects walk in the dark with their head held in different
      orientations. Depending on head orientation, we can either steer walking by
      "remote control" or produce balance disturbances. This shows that the brain
      resolves the canal signal according to head posture into Earth-referenced
      orthogonal components and uses rotations in vertical planes to control balance
      and rotations in the horizontal plane to navigate. Because the semicircular
      canals are concerned with movement rather than detecting vertical alignment, this
      result shows the importance of movement control and agility rather than precise
      vertical alignment of the body for human bipedalism.

PMID- 16890527
TI  - ROCK- and myosin-dependent matrix deformation enables protease-independent tumor
      cell invasion in vivo.
AB  - Tumor cells invading three-dimensional matrices need to remodel the extracellular
      matrix (ECM) in their path. Many studies have focused on the role of
      extracellular proteases; however, cells with amoeboid or rounded morphologies are
      able to invade even when these enzymes are inhibited. Here, we describe the
      mechanism by which cells move through a dense ECM without proteolysis. Amoeboid
      tumor cells generate sufficient actomyosin force to deform collagen fibers and
      are able to push through the ECM. Force generation is elevated in metastatic
      MTLn3E cells, and this correlates with increased invasion and altered myosin
      light chain (MLC) organization. In metastatic cells, MLC is organized
      perpendicularly to the direction of movement behind the invading edge. Both the
      organization of MLC and force generation are dependent upon ROCK function. We
      demonstrate that ROCK regulates the phosphorylation of MLC just behind the
      invading margin of the cell. Imaging of live tumors shows that MLC is organized
      in a similar ROCK-dependent fashion in vivo and that inhibition of ROCK but not
      matrix-metalloproteases reduces cancer cell motility in vivo.

PMID- 16890528
TI  - Drosophila dorsal paired medial neurons provide a general mechanism for memory
      consolidation.
AB  - Memories are formed, stabilized in a time-dependent manner, and stored in neural
      networks. In Drosophila, retrieval of punitive and rewarded odor memories depends
      on output from mushroom body (MB) neurons, consistent with the idea that both
      types of memory are represented there. Dorsal Paired Medial (DPM) neurons
      innervate the mushroom bodies, and DPM neuron output is required for the
      stability of punished odor memory. Here we show that stable reward-odor memory is
      also DPM neuron dependent. DPM neuron expression of amnesiac (amn) in amn mutant
      flies restores wild-type memory. In addition, disrupting DPM neurotransmission
      between training and testing abolishes reward-odor memory, just as it does with
      punished memory. We further examined DPM-MB connectivity by overexpressing a
      DScam variant that reduces DPM neuron projections to the MB alpha, beta, and
      gamma lobes. DPM neurons that primarily project to MB alpha' and beta' lobes are
      capable of stabilizing punitive- and reward-odor memory, implying that both forms
      of memory have similar circuit requirements. Therefore, our results suggest that
      the fly employs the local DPM-MB circuit to stabilize punitive- and reward-odor
      memories and that stable aspects of both forms of memory may reside in mushroom
      body alpha' and beta' lobe neurons.

PMID- 16890530
TI  - Asymmetric microtubule pushing forces in nuclear centering.
AB  - Dynamic properties of microtubules contribute to the establishment of spatial
      order within cells. In the fission yeast Schizosaccharomyces pombe, interphase
      cytoplasmic microtubules are organized into antiparallel bundles that attach to
      the nuclear envelope and are needed to position the nucleus at the geometric
      center of the cell. Here, we show that after the nucleus is displaced by cell
      centrifugation, these microtubule bundles efficiently push the nucleus back to
      the center. Asymmetry in microtubule number, length, and dynamics contributes to
      the generation of force responsible for this unidirectional movement. Notably,
      microtubules facing the distal cell tip are destabilized when the microtubules in
      the same bundle are pushing from the proximal cell tip. The CLIP-170-like protein
      tip1p and the microtubule-bundling protein ase1p are required for this asymmetric
      regulation of microtubule dynamics, indicating contributions of factors both at
      microtubule plus ends and within the microtubule bundle. Mutants in these factors
      are defective in nuclear movement. Thus, cells possess an efficient microtubule
      based engine that produces and senses forces for centering the nucleus. These
      studies may provide insights into mechanisms of asymmetric microtubule behaviors
      and force sensing in other processes such as chromosome segregation and cell
      polarization.

PMID- 16890529
TI  - Coordination of endoplasmic reticulum and mRNA localization to the yeast bud.
AB  - Localization of messenger RNAs and local protein synthesis contribute to
      asymmetric protein distribution not only of cytoplasmic but also of membrane or
      secreted proteins. Since synthesis of the latter protein classes occurs at the
      rough endoplasmic reticulum (ER), mRNA localization and distribution of ER should
      be coordinated. However, this coordination is not yet understood. In yeast, mRNA
      localization to the growing bud depends on the myosin Myo4p, its adaptor She3p,
      and the specific RNA binding protein She2p. These proteins mediate the
      localization of 23 mRNAs including ASH1 mRNA and mRNAs encoding membrane
      proteins. In addition, Myo4p and She3p are required for segregation of cortical
      ER to the bud. Here we show, with ASH1 mRNA as a model mRNA, that localizing
      messenger ribonucleoprotein (mRNP) particles comigrate with tubular ER structures
      to the bud, which requires the RNA binding protein She2p. Coordinated movement of
      the ASH1 mRNP with ER tubules but not their association with each other depends
      on Myo4p and She3p. Subcellular fractionation experiments demonstrate a
      cosegregation of ER and She2p, which is independent of Myo4p, She3p, or
      polysomes. Our findings suggest a novel model for mRNA localization that involves
      association of She2p and mRNPs with ER tubules and myosin-dependent cotransport
      of tubules and localized mRNPs.

PMID- 16890531
TI  - Telomere and telomerase modulation by the mammalian Rad9/Rad1/Hus1 DNA-damage
      checkpoint complex.
AB  - Telomeres, the termini of linear chromosomes, are exceptional in that they are
      DNA ends that do not normally trigger a DNA-damage response (DDR) and are
      compatible with normal cellular proliferation. Mammalian telomeres are
      nevertheless a physiological substrate of the DDR apparatus, as shown by the fact
      that the inactivation of genes encoding certain DDR factors results in telomere
      dysfunction. However, how DDR factors are integrated with telomere physiology,
      including telomere length regulation by the specialized reverse transcriptase
      telomerase, is still largely unclear. Here we report that the mammalian
      Rad9/Rad1/Hus1 (911) checkpoint complex, which localizes to sites of genome
      damage and promotes DDR signaling, is an integral component of the telomere in
      human and mouse cells. By the use of quantitative telomere-length measurements,
      we demonstrate severe telomeric shortening in both Hus1-deficient mouse embryonic
      fibroblasts and thymocytes from conditional Hus1-knockout mice. We also show that
      911 is found in association with catalytically competent telomerase in cell
      lysates and is a positive regulator of its DNA polymerase activity. These
      findings identify an unanticipated function for the 911 checkpoint complex at
      telomeres in mammals and provide a mechanistic link between the activity of DNA
      damage-checkpoint proteins and the telomere-maintenance machinery.

PMID- 16890532
TI  - Tumor formation via loss of a molecular motor protein.
AB  - Aneuploidy has long been suggested to be causal in tumor formation. Direct
      testing of this hypothesis has been difficult because of the absence of methods
      to specifically induce aneuploidy. The chromosome-associated kinesin motor KIF4
      plays multiple roles in mitosis, and its loss leads to multiple mitotic defects
      including aneuploidy. Here, we have taken advantage of the direct formation of
      aneuploidy in the absence of KIF4 to determine whether loss of a molecular motor
      and generation of aneuploidy during mitosis can trigger tumorigenesis. We find
      that embryonic stem cells genetically depleted of KIF4 support anchorage
      independent growth and form tumors in nude mice. In cells lacking KIF4, mitotic
      spindle checkpoints and DNA-damage response pathways are activated. Down
      regulation or loss of KIF4 is physiologically relevant because reduced KIF4
      levels are present in 35% of human cancers from several tissues. Our results
      support the notion that loss of a molecular motor leads to tumor formation and
      that aneuploidy can act as a primary trigger of tumorigenesis.

PMID- 16890533
TI  - Murine retrovirus escapes from murine APOBEC3 via two distinct novel mechanisms.
AB  - APOBEC3G (A3G) is an antiretroviral host factor that functions by deaminating dC
      to dU in retroviral cDNA. HIV-1 Vif protein counteracts A3G via a ubiquitin
      proteasome pathway. In the case of a simple retrovirus such as the murine
      leukemia virus (MLV), it remains unclear why it can replicate in cells expressing
      APOBEC3 (A3) even though it doesn't possess any accessory proteins such as Vif.
      In this study, we demonstrate that MLV escapes from murine A3 (mA3) via two
      distinct novel mechanisms. First, viral RNA (vRNA) blocks the binding of mA3 to
      Gag, resulting in the exclusion of mA3 from MLV virions. Second, viral protease
      (vPR) cleaves mA3 after maturation of virions. Here, we suggest that each virus
      has its own strategy to escape from A3 proteins and that these mechanisms might
      be used by other viruses that do not possess Vif-like protein. On the other hand,
      mice possess another form of mA3, delta exon5, that escapes from the cleavage by
      vPR to show more antiviral activity than the wild type mA3. This also suggests
      that battles between host intrinsic immunity and viruses have led to the
      evolution of proteins on both sides.

PMID- 16890534
TI  - Live-cell imaging reveals a stable cohesin-chromatin interaction after but not
      before DNA replication.
AB  - Cohesin is a multisubunit protein complex that links sister chromatids from
      replication until segregation. The lack of obvious cohesin-targeting-specific
      sequences on DNA, as well as cohesin's molecular arrangement as a large ring, has
      led to the working hypothesis that cohesin acts as a direct topological linker.
      To preserve the identity of sister chromatids, such a linkage would need to
      stably persist throughout the entire S and G2 phases of the cell cycle.
      Unexpectedly, cohesin binds chromatin already in telophase, and a large fraction
      dissociates from chromosomes during prophase in a phosphorylation-dependent
      manner, whereas initiation of anaphase requires proteolytic cleavage of only a
      small fraction of cohesin. These observations raised the question of how and when
      cohesin interacts with chromatin during the cell cycle. Here, we report a cell
      cycle dependence in the stability of cohesin binding to chromatin. Using
      photobleaching and quantitative live-cell imaging, we identified several cohesin
      pools with different chromatin binding stabilities. Although all chromatin bound
      cohesin dissociated after a mean residence time of less than 25 min before
      replication, about one-third of cohesin was bound much more stably after S phase
      and persisted until metaphase, consistent with long-lived links mediating
      cohesion between sister chromatids.

PMID- 16890535
TI  - Precious metal economy.
AB  - The zebrafish is emerging as a system of choice for modeling human disease. In
      this issue of Cell Metabolism, Mendelsohn et al. (2006) describe a model for
      Menkes disease, a genetic disorder in copper utilization. Using genetic and
      chemical screens, the authors highlight the impact of maternal nutrition on
      embryo development. The work reveals a hierarchy of temporal and dosage-dependent
      phenotypes for copper nutrition.

PMID- 16890536
TI  - The murmur of old broken heartstrings.
AB  - Although it has long been hypothesized that gene expression might become more
      variable or noisy during aging, direct evidence has been scarce so far. A new
      study reports detection, by PCR analysis of individual cells, of increased cell
      to-cell variability in gene expression in aging mouse heart; moreover, a similar
      variability can be generated in cultured cells using oxidative stress (Bahar et
      al., 2006).

PMID- 16890537
TI  - Dirty dealing: hepatic vagal afferents reshuffle fat distribution.
AB  - To evaluate the role of hepatic peroxisome-proliferator-activated receptor (PPAR)
      gamma 2 in the control of energy balance, Uno and colleagues examined the
      metabolic effects of overexpression of PPAR gamma 2 selectively in mouse and rat
      liver. Mice demonstrated a surprising degree of hepatic steatosis accompanied by
      significant reductions in peripheral adiposity. This crosstalk between liver and
      adipose tissue appears to be mediated by both the sensory component of the
      hepatic vagus nerve and sympathetic efferents. These data suggest a novel hepatic
      adipose neuraxis that regulates the distribution of stored fat.

PMID- 16890538
TI  - Carbohydrate response element binding protein, ChREBP, a transcription factor
      coupling hepatic glucose utilization and lipid synthesis.
AB  - The ability of an organism to sense and store nutrients is vital to survival. The
      liver is the major organ responsible for converting excess dietary carbohydrate
      to lipid for storage. An elegant molecular pathway has evolved that allows
      increased glucose flux into hepatocytes to generate a signaling molecule,
      xylulose 5-phosphate, that triggers rapid changes in glycolytic enzyme activities
      and nuclear import of a transcription factor, ChREBP, which coordinates the
      transcriptional regulation of enzymes that channel the glycolytic end-products
      into lipogenesis. Further understanding of this metabolic cascade should provide
      insights on conditions such as fatty liver, obesity, and the metabolic syndrome.

PMID- 16890539
TI  - Bidirectional ephrinB2-EphB4 signaling controls bone homeostasis.
AB  - Bone homeostasis requires a delicate balance between the activities of bone
      resorbing osteoclasts and bone-forming osteoblasts. Various molecules coordinate
      osteoclast function with that of osteoblasts; however, molecules that mediate
      osteoclast-osteoblast interactions by simultaneous signal transduction in both
      cell types have not yet been identified. Here we show that osteoclasts express
      the NFATc1 target gene Efnb2 (encoding ephrinB2), while osteoblasts express the
      receptor EphB4, along with other ephrin-Eph family members. Using gain- and loss
      of-function experiments, we demonstrate that reverse signaling through ephrinB2
      into osteoclast precursors suppresses osteoclast differentiation by inhibiting
      the osteoclastogenic c-Fos-NFATc1 cascade. In addition, forward signaling through
      EphB4 into osteoblasts enhances osteogenic differentiation, and overexpression of
      EphB4 in osteoblasts increases bone mass in transgenic mice. These data
      demonstrate that ephrin-Eph bidirectional signaling links two major molecular
      mechanisms for cell differentiation--one in osteoclasts and the other in
      osteoblasts--thereby maintaining bone homeostasis.

PMID- 16890540
TI  - Enhanced leptin sensitivity and improved glucose homeostasis in mice lacking
      suppressor of cytokine signaling-3 in POMC-expressing cells.
AB  - Suppressor of cytokine signaling-3 (Socs-3) negatively regulates the action of
      various cytokines, as well as the metabolic hormones leptin and insulin. Mice
      with haploinsufficiency of Socs-3, or those with neuronal deletion of Socs-3, are
      lean and more leptin and insulin sensitive. To examine the role of Socs-3 within
      specific neurons critical to energy balance, we created mice with selective
      deletion of Socs-3 within pro-opiomelanocortin (POMC)-expressing cells. These
      mice had enhanced leptin sensitivity, measured by weight loss and food intake
      after leptin infusion. On chow diet, glucose homeostasis was improved despite
      normal weight gain. On a high-fat diet, the rate of weight gain was reduced, due
      to increased energy expenditure rather than decreased food intake; glucose
      homeostasis and insulin sensitivity were substantially improved. These studies
      demonstrate that Socs-3 within POMC neurons regulates leptin sensitivity and
      glucose homeostasis, and plays a key role in linking high-fat diet to disordered
      metabolism.

PMID- 16890541
TI  - Activated FOXO-mediated insulin resistance is blocked by reduction of TOR
      activity.
AB  - Reducing insulin/IGF signaling allows for organismal survival during periods of
      inhospitable conditions by regulating the diapause state, whereby the organism
      stockpiles lipids, reduces fertility, increases stress resistance, and has an
      increased lifespan. The Target of Rapamycin (TOR) responds to changes in growth
      factors, amino acids, oxygen tension, and energy status; however, it is unclear
      how TOR contributes to physiological homeostasis and disease conditions. Here, we
      show that reducing the function of Drosophila TOR results in decreased lipid
      stores and glucose levels. Importantly, this reduction of dTOR activity blocks
      the insulin resistance and metabolic syndrome phenotypes associated with
      increased activity of the insulin responsive transcription factor, dFOXO.
      Reduction in dTOR function also protects against age-dependent decline in heart
      function and increases longevity. Thus, the regulation of dTOR activity may be an
      ancient "systems biological" means of regulating metabolism and senescence, that
      has important evolutionary, physiological, and clinical implications.

PMID- 16890542
TI  - Granuphilin is activated by SREBP-1c and involved in impaired insulin secretion
      in diabetic mice.
AB  - Granuphilin is a crucial component of the docking machinery of insulin-containing
      vesicles to the plasma membrane. Here, we show that the granuphilin promoter is a
      target of SREBP-1c, a transcription factor that controls fatty acid synthesis,
      and MafA, a beta cell differentiation factor. Potassium-stimulated insulin
      secretion (KSIS) was suppressed in islets with adenoviral-mediated overexpression
      of granuphilin and enhanced in islets with knockdown of granuphilin (in which
      granuphilin had been knocked down). SREBP-1c and granuphilin were activated in
      islets from beta cell-specific SREBP-1c transgenic mice, as well as in several
      diabetic mouse models and normal islets treated with palmitate, accompanied by a
      corresponding reduction in insulin secretion. Knockdown- or knockout-mediated
      ablation of granuphilin or SREBP-1c restored KSIS in these islets. Collectively,
      our data provide evidence that activation of the SREBP-1c/granuphilin pathway is
      a potential mechanism for impaired insulin secretion in diabetes, contributing to
      beta cell lipotoxicity.

PMID- 16890544
TI  - The circadian rhythm of glucocorticoids is regulated by a gating mechanism
      residing in the adrenal cortical clock.
AB  - In mammals, the master clock of the suprachiasmatic nuclei (SCN) and subordinate
      clocks found throughout the body coordinate circadian rhythms of behavior and
      physiology. We characterize the clock of the adrenal, an important endocrine
      gland that synchronizes physiological and metabolic rhythms. Clock gene
      expression was detected in the outer adrenal cortex prefiguring a role of the
      clock in regulating gluco- and mineral corticoid biogenesis. In Per2/Cry1 double
      mutant mice, which lack a circadian clock, hypothalamus/pituitary/adrenal axis
      regulation was defective. Organ culture and tissue transplantation suggest that
      the adrenal pacemaker gates glucocorticoid production in response to
      adrenocorticotropin (ACTH). In vivo the adrenal circadian clock can be entrained
      by light. Transcriptome profiling identified rhythmically expressed genes located
      at diverse nodes of steroid biogenesis that may mediate gating of the ACTH
      response by the adrenal clock.

PMID- 16890543
TI  - Atp7a determines a hierarchy of copper metabolism essential for notochord
      development.
AB  - The critical developmental and genetic requirements of copper metabolism during
      embryogenesis are unknown. Utilizing a chemical genetic screen in zebrafish, we
      identified small molecules that perturb copper homeostasis. Our findings reveal a
      role for copper in notochord formation and demonstrate a hierarchy of copper
      metabolism within the embryo. To elucidate these observations, we interrogated a
      genetic screen for embryos phenocopied by copper deficiency, identifying
      calamity, a mutant defective in the zebrafish ortholog of the Menkes disease gene
      (atp7a). Copper metabolism in calamity is restored by human ATP7A, and
      transplantation experiments reveal that atp7a functions cell autonomously,
      findings with important therapeutic implications. The gene dosage of atp7a
      determines the sensitivity to copper deprivation, revealing that the observed
      developmental hierarchy of copper metabolism is informed by specific genetic
      factors. Our data provide insight into the developmental pathophysiology of
      copper metabolism and suggest that suboptimal copper metabolism may contribute to
      birth defects.

PMID- 16890546
TI  - Congenital urogenital anomalies that are associated with the persistence of
      Gartner's duct: a review.
AB  - The embryogenesis and management of congenital urogenital anomalies that are
      associated with ureteric ectopia and the persistence of Gartner's duct are
      discussed. Ureteric ectopia with Gartner's duct cyst is caused by the failure of
      separation of the ureteric bud from the mesonephric duct, which leads to
      persistence of Gartner's duct, frequently with cystic dilation. Abnormal
      development of the ureter subsequently causes maldevelopment or absence of the
      ipsilateral kidney. The diagnosis and treatment of 2 adult women with congenital
      urethrovaginal fistula that was associated with unilateral single ectopic ureter,
      renal agenesis, and Gartner's duct anomaly are presented. Surgical repair of the
      urethrovaginal fistulae and removal of the Gartner's duct and cyst was performed
      transvaginally.

PMID- 16890545
TI  - Predicting absolute risk of CIN3 during post-colposcopic follow-up: results from
      the ASCUS-LSIL Triage Study (ALTS).
AB  - OBJECTIVE: At present, clinical management of women referred to colposcopy but
      found to have <CIN2 remains unclear. Using data from the ASCUS-LSIL Triage Study
      (ALTS) to inform clinical management, we calculated the absolute risk for
      developing CIN3 within 2 years of referral to an enrollment colposcopy. STUDY
      DESIGN: Women included in the analyses: (1) were initially referred to ALTS with
      a community cytologic interpretation of atypical squamous cell of undetermined
      significance (ASCUS) or low-grade squamous intraepithelial lesions (LSIL); (2)
      had a colposcopic evaluation and biopsy, if indicated, resulting in a diagnosis
      <CIN2; and, therefore (3) were followed without treatment. Results from
      subsequent human papillomavirus (HPV) testing, liquid-based cytology
      interpretations, and a second colposcopic evaluation at least 6 months after and
      within 2 years of the first colposcopic evaluation were used to calculate
      absolute risks for CIN3. RESULTS: Women with HPV-negative test results were at
      low risk for CIN3 regardless of other test results. Among HPV-positive women,
      increasing absolute risks of CIN3 were observed with increasing cytology
      severity: 7% (normal), 11% (ASCUS and LSIL), and 45% (HSIL). The highest absolute
      risk for CIN3 (67%) was observed for HPV-positive women with HSIL and a
      colposcopic impression of high-grade/cancer on the second colposcopy. CONCLUSION:
      In the ALTS population, after the first colposcopic diagnosis of <CIN2, clear
      risk stratification for CIN3 outcomes was obtained among women with a subsequent
      HPV-positive test. Because absolute risk for histologic CIN3 outcomes was high
      for women with HPV positive tests, HSIL cytology, and a high-grade impression at
      second colposcopy, it is worth considering whether this combination of findings
      might warrant immediate excisional therapy in some circumstances.

PMID- 16890547
TI  - High-dimensional biology in obstetrics and gynecology: functional genomics in
      microarray studies.

PMID- 16890549
TI  - Human spontaneous labor without histologic chorioamnionitis is characterized by
      an acute inflammation gene expression signature.
AB  - OBJECTIVE: The purpose of this study was to identify which biological processes
      may be involved in normal labor. STUDY DESIGN: Transcriptional profiles for
      chorioamniotic membranes (n = 24) and blood (n = 20) were generated from patients
      at term with no labor (TNL) and in labor (TIL). RESULTS: Expression of 197
      transcripts (P < or = .02) differentiated TIL and TNL chorioamniotic membrane
      samples. Gene Ontology analysis indicated that TIL samples had increased
      expression of multiple chemokines and transcripts associated with neutrophil and
      monocyte recruitment. Microarray results were verified using quantitative real
      time reverse transcription polymerase chain reaction (RT-PCR) with independent
      samples. Transcriptional profiles from blood RNA revealed no Gene Ontology
      category enrichment of discriminant probe sets. CONCLUSION: Labor induces gene
      expression changes consistent with localized inflammation, despite the absence of
      histologically detectable inflammation.

PMID- 16890551
TI  - Determinants of long-term clinically detected recurrence rates of deep, ovarian,
      and pelvic endometriosis.
AB  - OBJECTIVE: This study was undertaken to analyze the frequency and the
      determinants of long-term clinically detectable recurrence rate of deep, ovarian,
      and pelvic endometriosis. STUDY DESIGN: The clinical data of 1106 women with
      first diagnosis of endometriosis observed between 1979 and 2001 were collected.
      RESULTS: The 4-year recurrence rate was 24.6%, 17.8%, 30.6% and 23.7%,
      respectively, for cases of ovarian, pelvic, deep, and ovarian and pelvic
      endometriosis (P < .05). The recurrence rates decreased in all groups (with the
      exception of ovarian endometriosis) in the class age 34 years or older, these
      findings were significant (P < .05). Radicality was associated with lower
      recurrence rates in all the groups. A pregnancy after diagnosis was associated
      with a reduced risk of recurrence. CONCLUSION: The study shows that the
      recurrence rates of endometriosis were higher in case of deep endometriosis and
      that the risk factors for recurrence were similar among women with endometriosis
      at different sites.

PMID- 16890550
TI  - Gene expression profiling of mid to late secretory phase endometrial biopsies
      from women with menstrual complaint.
AB  - OBJECTIVE: The purpose of this study was to test whether a quantitative high
      throughput molecular screen can be used to probe human endometrium and initiate
      the development of molecular diagnostic tools with potential for identification
      of therapeutic targets in women with menstrual complaints. STUDY DESIGN:
      Endometrium was collected from 10 patients with complaint of heavy bleeding,
      classified into mid or late secretory phase of the menstrual cycle by histologic
      dating and serum progesterone concentration. Total RNA was extracted and gene
      activity assessed using high-density oligonucleotide arrays. RESULTS: Statistical
      testing identified 83 'signature' genes whose expression levels differentiated
      the mid and late secretory phases of the menstrual cycle. CONCLUSION: The results
      show that the endometrium, a complex heterogeneous tissue, is amenable to high
      throughput molecular analyses and this work provides further support for the
      future application of molecular profiling to clinical diagnosis.

PMID- 16890552
TI  - Urinary incontinence and age at the first and last delivery: the Norwegian
      HUNT/EPINCONT study.
AB  - OBJECTIVE: This study was undertaken to investigate the association between
      maternal age at the first and last delivery, and urinary incontinence later in
      life. STUDY DESIGN: In the Norwegian EPINCONT study (a substudy of HUNT 2), cross
      sectional data on incontinence from 11,397 women aged 20 to 64 years was linked
      with prospectively obtained data on exposures from the Medical Birth Registry of
      Norway. Bivariate and multivariate methods were applied. RESULTS: Women 25 years
      or younger at their first delivery had a lower risk of incontinence than their
      older counterparts (23% vs 28%, P < .01). No significant effect of maternal age
      at the first delivery was found in women with actual age 50 to 64 years.
      Adjusting for confounders did not change any results. Age at the last delivery
      was less associated with incontinence. CONCLUSION: Being older than 25 years at
      the first delivery was associated with incontinence. The effect attenuated with
      actual age.

PMID- 16890553
TI  - Ovarian interstitial YAG-laser: an effective new method to manage anovulation in
      women with polycystic ovary syndrome.
AB  - OBJECTIVE: This study was undertaken to assess the effectiveness of transvaginal
      ultrasound-guided ovarian interstitial laser-coagulation treatment in anovulatory
      women with polycystic ovary syndrome (PCOS). STUDY DESIGN: Nineteen anovulatory
      women with clomiphene citrate-resistant PCOS underwent ultrasound-guided
      transvaginal ovarian interstitial YAG-laser treatment. In this study, serum
      hormonal level, spontaneous ovulation rate, and pregnancy rate were assessed.
      RESULTS: With a spontaneous ovulation rate of 84.2%, 16 of 19 cases ovulated
      regularly during the 6-month postoperative period. The mean serums luteinizing
      hormone and serum testosterone levels in the second, fourth, and sixth
      postoperative months were significantly lower than preoperative levels: 5.87 +/-
      2.04 IU/L versus 13.17 +/- 3.03 IU/L (P < .001) and 2.98 +/- 1.79 nmol/L versus
      5.49 +/- 3.23 nmol/L (P < .001), respectively. The mean luteinizing
      hormone/follicle-stimulating hormone ratio was also significantly lower
      postoperatively at 1.09 +/- 0.30 compared with the preoperative 2.85 +/- 1.14 (P
      < .001). There was a cumulative pregnancy rate at 6 months of 32.3% (6/19) among
      the subjects. No significant operative complications were encountered.
      CONCLUSION: The ultrasound-guided transvaginal ovarian interstitial laser
      treatment may be an effective new method to manage anovulation in PCOS patients.

PMID- 16890548
TI  - Analysis of microarray experiments of gene expression profiling.
AB  - The study of gene expression profiling of cells and tissue has become a major
      tool for discovery in medicine. Microarray experiments allow description of
      genome-wide expression changes in health and disease. The results of such
      experiments are expected to change the methods employed in the diagnosis and
      prognosis of disease in obstetrics and gynecology. Moreover, an unbiased and
      systematic study of gene expression profiling should allow the establishment of a
      new taxonomy of disease for obstetric and gynecologic syndromes. Thus, a new era
      is emerging in which reproductive processes and disorders could be characterized
      using molecular tools and fingerprinting. The design, analysis, and
      interpretation of microarray experiments require specialized knowledge that is
      not part of the standard curriculum of our discipline. This article describes the
      types of studies that can be conducted with microarray experiments (class
      comparison, class prediction, class discovery). We discuss key issues pertaining
      to experimental design, data preprocessing, and gene selection methods. Common
      types of data representation are illustrated. Potential pitfalls in the
      interpretation of microarray experiments, as well as the strengths and
      limitations of this technology, are highlighted. This article is intended to
      assist clinicians in appraising the quality of the scientific evidence now
      reported in the obstetric and gynecologic literature.

PMID- 16890554
TI  - The disruptive physician: myth of reality.

PMID- 16890555
TI  - Outcomes of octogenarians and nonagenarians in elective major gynecologic
      surgery.
AB  - OBJECTIVE: The purpose of this study was to determine whether age is a risk
      factor for perioperative and postoperative complications. STUDY DESIGN: This was
      a retrospective case-control study of 120 women over age 79 (group 1) compared
      with 1,497 younger patients 50-79 (group 2) undergoing major elective gynecologic
      surgery. RESULTS: Mean length of stay was 4.8 days for group 1, compared with 3.8
      for group 2 (P = .018). Patients hospitalized longer than 1 week was higher (P <
      .01) among group 1. There were statistically significant increases in UTI,
      psychiatric events, pulmonary edema, respiratory failure, sepsis, and hypovolemic
      shock. No significant difference in mortality rate was noted (group 1: 0.83%, n =
      1 vs group 2: 0.47%, n = 7). CONCLUSION: Although length of stay for the elderly
      is slightly increased, mortality and complication rates are comparable to younger
      patients with few exceptions. We conclude that age need not be the sole
      determinant in the decision to undergo major elective gynecologic surgery.

PMID- 16890558
TI  - Initial chemotherapy followed by surgical cytoreduction for the treatment of
      stage III/IV epithelial ovarian cancer.
AB  - OBJECTIVE: The purpose of this study was to evaluate differences in morbidity,
      progression-free interval, and survival in women with advanced epithelial ovarian
      cancer treated with initial chemotherapy versus initial surgery. STUDY DESIGN:
      All women with epithelial ovarian cancer who were treated surgically at our
      hospital between January 1, 1995, and January 1, 2003, were eligible; the cases
      of 200 patients met the criteria and underwent retrospective chart review.
      RESULTS: Ninety-eight patients (49%) had initial chemotherapy, and 102 patients
      (51%) had initial surgery. Patients who received initial chemotherapy were more
      likely to have stage IV disease (initial chemotherapy, 27%, vs initial surgery,
      8%; P = .042) and grade 3 disease (initial chemotherapy, 73%, vs initial surgery,
      61%; P = .025). Optimal cytoreduction was achieved more often in patients who
      received initial chemotherapy (initial chemotherapy, 86%, vs initial surgery,
      54%; P < .001). Only optimal cytoreduction (P = .022), and not treatment choice
      (P = .089), had an impact on median survival. CONCLUSION: Initial chemotherapy is
      a reasonable alternative to initial surgery for the treatment of selected
      patients with advanced epithelial ovarian cancer.

PMID- 16890561
TI  - Institution and validation of an observed structured assessment of technical
      skills (OSATS) for obstetrics and gynecology residents and faculty.
AB  - OBJECTIVE: This study was undertaken to further evaluate the construct validity
      of the observed structured assessment of technical skills (OSATS) by comparing
      resident scores to faculty scores. STUDY DESIGN: This study is a prospective
      blinded observational study. Four residents from each year (1-4) and 5 faculty
      members were examined. The OSATS examination was in the form of a dry laboratory
      with 10 stations: 4 laparoscopic and 6 open surgical skills. The sessions were
      videotaped and graded by the senior authors who used a task-specific checklist.
      The scoring of the videos was performed by the 2 senior authors blinded to the
      other examiners results. The examinations were videotaped, and the identity of
      the participants was blinded. The scores for each station were determined by
      adding all the numbers from the skills rating with a time score. Higher scores
      denote superior performance. Statistical analysis was performed with a
      nonparametric test (Kruskal-Wallis) for a total score with resident years divided
      into junior residents (first and second year), senior residents (third and fourth
      year), and faculty status as the independent variable. To determine the
      interrelater reliability between the 2 scores, the Kendall tau beta statistic was
      used. RESULTS: The results show definite trends for 7 stations, with junior
      residents performing the worst and faculty performing the best. This trend was
      statistically significant for 6 of the 10 stations. CONCLUSION: The OSATS
      examination has good construct validity that extends beyond residency to faculty.

PMID- 16890564
TI  - Preoperative vaginal preps with chlorhexidine gluconate solution.

PMID- 16890565
TI  - Words matter: the importance of nondirective language in first-trimester
      assessments for Down syndrome.

PMID- 16890568
TI  - Reconsidering anticoagulation issue of pregnant women with mitral stenosis.

PMID- 16890570
TI  - Brachial plexus deficits with and without shoulder dystocia.

PMID- 16890572
TI  - Reduction in hematocrit level after pioglitazone treatment is correlated with
      decreased plasma free testosterone level, not hemodilution, in women with
      polycystic ovary syndrome.
AB  - Thiazolidinediones have gained widespread use for the treatment of type 2
      diabetes mellitus and other insulin resistance states, including polycystic ovary
      syndrome (PCOS). In thiazolidinedione-treated patients a small reduction in
      hemoglobin and hematocrit levels often is observed, and this generally has been
      attributed to fluid retention. Because testosterone is a hematopoietic hormone,
      we investigated whether a reduction in plasma free testosterone concentration was
      associated with the decrease in hemoglobin and hematocrit levels in 22
      nondiabetic women (9 with normal glucose tolerance and 13 with impaired glucose
      tolerance; mean age, 29 +/- 5 years; mean body mass index, 35.6 +/- 5.8 kg/m2)
      with PCOS who were treated with pioglitazone, 45 mg/d. Before treatment and after
      4 months, subjects underwent an oral glucose tolerance test and measurement of
      total body water content with bioimpedance. Plasma testosterone, androstenedione,
      dehydroepiandrosterone sulfate, hemoglobin, and hematocrit levels were evaluated
      at baseline and every month for 4 months. The fasting plasma glucose
      concentration (98 +/- 9 mg/dL) was unchanged after pioglitazone treatment,
      whereas the 2-hour plasma glucose concentration declined from 146 +/- 41 to 119
      +/- 20 mg/dL (P = .002). Both the free androgen index and the free testosterone
      levels calculated according to Vermeulen et al decreased significantly (from 14.4
      +/- 7.1 to 10.6 +/- 7.8 [P = .02] and from 59.4 +/- 23.4 to 46.6 +/- 23.3 [P =
      .03], respectively). The plasma androstenedione level declined from 259 +/- 134
      to 190 +/- 109 ng/dL (P = .01), whereas the dehydroepiandrosterone sulfate level
      did not change significantly (from 139 +/- 90 to 127 +/- 84 mug/dL, P = .2 [not
      significant]). The levels of both hemoglobin (from 13.6 +/- 1.0 to 12.8 +/- 1.1
      g/dL, P = .0002) and hematocrit (from 39.7% +/- 2.2% to 37.9% +/- 2.7%, P = .002)
      fell slightly after 4 months of pioglitazone administration. Collectively, before
      and after pioglitazone administration, the plasma free testosterone level
      according to Vermeulen et al correlated positively with the levels of hemoglobin
      (r = 0.49, P < .0001) and hematocrit (r = 0.40, P < .0001), as well as the free
      androgen index (r = 0.38 [P < .0003] with hemoglobin and r = 0.29 [P < .006] with
      hematocrit); the decrement in plasma free testosterone level and free androgen
      index also correlated with the decrements in the levels of both hemoglobin (r =
      0.51 [P = .01] and r = 0.54 [P = .01], respectively) and hematocrit (r = 0.42 [P
      = .05] and r = 0.50 [P = .02], respectively). Body weight increased from 90.5 +/-
      17.3 to 92.4 +/- 18.8 kg after pioglitazone administration (P = .05), as did body
      fat content (from 42.7 +/- 15.3 to 44.8 +/- 17.1 kg, P = .03), which could
      explain the increase in weight, because edema did not develop in any of the
      subjects. Total body water content did not change significantly after
      pioglitazone administration (from 37.7 +/- 5.0 to 37.8 +/- 4.9 L, P = .68 [not
      significant]). In summary, pioglitazone treatment is associated with a mild
      decline in hematocrit or hemoglobin level, which is correlated with the reduction
      in plasma testosterone level. These results suggest that increased body water
      content cannot explain the reduction in hematocrit or hemoglobin level in women
      with PCOS. Further studies are necessary to evaluate whether the same scenario is
      applicable to normoandrogenic women and individuals with type 2 diabetes
      mellitus.

PMID- 16890573
TI  - Heterogeneity in the suppression of platelet cyclooxygenase-1 activity by aspirin
      in coronary heart disease.
AB  - BACKGROUND AND OBJECTIVES: Complete and persistent suppression of platelet
      thromboxane (TX) A(2) biosynthesis by aspirin is mandatory to fulfill its
      cardioprotection. We explored the determinants of heterogeneity of TXB2
      generation in clotting whole blood, a capacity index of platelet cyclooxygenase
      (COX) activity, in patients with coronary heart disease (CHD) versus healthy
      subjects treated with low-dose aspirin on a long-term basis. METHODS: We studied
      30 patients with CHD (ie, chronic stable angina, unstable angina, and acute
      myocardial infarction) and 10 healthy subjects, who were treated with low-dose
      aspirin (100 mg daily) on a long-term basis, 12 hours after the administration of
      160 mg aspirin to ensure saturation of platelet COX-1 activity. Serum TXB2 levels
      were assessed. The contribution of blood COX-2 to TXA2 biosynthesis was explored
      by evaluation of the effect of a selective COX-2 inhibitor (L-745,337) added to
      heparinized whole blood stimulated with Ca++ ionophore A23187 (20 micromol/L) for
      1 hour or lipopolysaccharide (0.1 microg/mL) for 4 hours. RESULTS: In healthy
      subjects serum TXB2 levels ranged from 0.6 to 7.9 ng/mL (median, 2.1 ng/mL; mean
      +/- SD, 3.2 +/- 2.6 ng/mL). In CHD patients we detected enhanced variability in
      serum TXB2 generation (median, 3.1 ng/mL [range, 0.15-47 ng/mL]; mean, 8.5 +/-
      12.3 ng/mL), which in 8 patients (27%) exceeded the mean value + 2 SDs detected
      in healthy subjects (ie, 8.4 ng/mL), set as the limit value for an adequate
      inhibition of platelet COX-1 by aspirin. Elevated whole-blood TXB2 generation was
      not dependent on leukocyte count, COX-2 activity, or cigarette smoking but was
      plausibly a result of defective suppression of platelet COX-1 activity.
      CONCLUSIONS: Heterogeneity in the suppression of platelet COX-1 activity by
      aspirin occurred in CHD patients. The measurement of the serum TXB2 level seems
      to be an appropriate biomarker to identify patients who have an inadequate
      inhibition of platelet COX-1 activity by aspirin.

PMID- 16890574
TI  - Potent cytochrome P450 2C19 genotype-related interaction between voriconazole and
      the cytochrome P450 3A4 inhibitor ritonavir.
AB  - OBJECTIVES: Cytochrome P450 (CYP) 2C19 and CYP3A4 are the major enzymes
      responsible for voriconazole elimination. Because the activity of CYP2C19 is
      under genetic control, the extent of inhibition with a CYP3A4 inhibitor was
      expected to be modulated by the CYP2C19 metabolizer status. This study thus
      assessed the effect of the potent CYP3A4 inhibitor ritonavir after short-term
      administration on voriconazole pharmacokinetics in extensive metabolizers (EMs)
      and poor metabolizers (PMs) of CYP2C19. METHODS: In a randomized, placebo
      controlled crossover study, 20 healthy participants who were stratified according
      to CYP2C19 genotype received oral ritonavir (300 mg twice daily) or placebo for 2
      days. Together with the first ritonavir or placebo dose, a single oral dose of
      400 mg voriconazole was administered. Voriconazole was determined in plasma and
      urine by liquid chromatography-mass spectrometry, and pharmacokinetic parameters
      were estimated by noncompartmental analysis. RESULTS: When given alone, the
      apparent oral clearance of voriconazole after single oral dosing was 26%+/-16% (P
      > .05) lower in CYP2C19*1/*2 individuals and 66%+/-14% (P < .01) lower in CYP2C19
      PMs. The addition of ritonavir caused a major reduction in voriconazole apparent
      oral clearance (354+/-173 mL/min versus 202+/-139 mL/min, P = .0001). This
      reduction occurred in all CYP2C19 genotypes (463+/-168 mL/min versus 305+/-112
      mL/min [P = .023] for *1/*1, 343+/-127 mL/min versus 190+/-93 mL/min [P = .008]
      for *1/*2, and 158+/-54 mL/min versus 22+/-11 mL/min for *2/*2) and is probably
      caused by inhibition of CYP3A4-mediated voriconazole metabolism. CONCLUSIONS:
      Coadministration of a potent CYP3A4 inhibitor leads to a higher and prolonged
      exposure with voriconazole that might increase the risk of the development of
      adverse drug reactions on a short-term basis, particularly in CYP2C19 PM
      patients.

PMID- 16890575
TI  - Clinical pharmacokinetics of erlotinib in patients with solid tumors and exposure
      safety relationship in patients with non-small cell lung cancer.
AB  - OBJECTIVE: Our objective was to assess the pharmacokinetics of erlotinib in a
      large patient population with solid tumors, identify covariates, and explore
      relationships between exposure and safety outcomes (rash and diarrhea) in
      patients with non-small cell lung cancer receiving single-agent erlotinib.
      METHODS: The population pharmacokinetic analysis was performed by use of NONMEM
      based on 4068 concentration samples from 1047 patients receiving erlotinib as a
      single agent or in combination with chemotherapy. By use of a 1-compartment model
      with first-order absorption, the influence of demographic and clinical
      characteristics on clearance and volume was examined. Spearman rank correlation
      analyses were performed to test for correlations between maximum grades of rash
      and diarrhea and erlotinib exposure in non-small cell lung cancer patients
      treated with single-agent erlotinib. RESULTS: On the basis of the final model
      developed from patients treated with erlotinib as a single agent, the oral
      clearance was 3.95 L/h, the oral volume of distribution was 233 L, and the
      absorption rate was 0.95 h(-1). The median erlotinib half-life based on this
      patient population was 36.2 hours. Total bilirubin, alpha1-acid glycoprotein, and
      smoking status were the most important factors affecting clearance. The clearance
      in current smokers was 24% faster than that in former smokers or those who never
      smoked. There was a statistically significant correlation between drug exposure
      and rash (P < .05). However, there was significant overlap in the range of values
      for patients who had no rash (grade = 0) and those who had any grade of rash. No
      significant correlation was found between exposure and diarrhea. CONCLUSIONS: The
      long half-life of erlotinib supports the current once-daily dosing regimen at 150
      mg/d. Effects of covariates on erlotinib clearance and correlations with adverse
      event severity were provided to aid in the detection of a treatment-emergent
      effect.

PMID- 16890577
TI  - Lopinavir/ritonavir reduces lamotrigine plasma concentrations in healthy
      subjects.
AB  - BACKGROUND: Limited data are available about the effect of lopinavir and low-dose
      ritonavir on glucuronidation. Lamotrigine undergoes glucuronidation. We studied
      the effect of lopinavir/ritonavir on the pharmacokinetics of lamotrigine and vice
      versa. METHODS: Twenty-four healthy subjects received 50 mg lamotrigine once
      daily on days 1 and 2 and 100 mg twice daily on day 3 through day 23. Lopinavir
      (400 mg twice daily)/ritonavir (100 mg twice daily) was added on day 11.
      Depending on the decrease in lamotrigine trough level between days 10 and 20,
      either the study was stopped (<20% decrease) or a dose increase was applied from
      day 23 to day 31, as follows: increase to 150 mg lamotrigine twice daily if there
      was a 20% to 33% decrease, increase to 200 mg twice daily if there was a 34% to
      66% decrease, and increase to 300 mg twice daily if there was a greater than 66%
      decrease. On days 10, 20, and 31, 12-hour pharmacokinetic curves were drawn.
      RESULTS: The mean decrease in lamotrigine trough level between days 10 and 20 was
      55.4% (n = 18). A dose increment to 200 mg lamotrigine twice daily was used in
      all subjects. The area under the plasma concentration-time curve (AUC) values of
      lamotrigine on day 20 (with lopinavir/ritonavir) and day 10 (without
      lopinavir/ritonavir) were bioinequivalent, with a point estimate of 0.50 (90%
      confidence interval, 0.47-0.54). After dose adjustment of lamotrigine to 200 mg
      twice daily, the AUC on day 31 (n = 15) was bioequivalent to that on day 10, with
      a point estimate of 0.91 (90% confidence interval, 0.82-1.02). The median AUC
      ratios of lamotrigine 2N-glucuronide to lamotrigine on day 10 and day 20 were
      0.57 (interquartile range, 0.39-0.75) and 1.12 (interquartile range, 0.87-1.31).
      Pharmacokinetic parameters for lopinavir/ritonavir were similar to historical
      controls. CONCLUSION: Lopinavir/ritonavir decreases the AUC of lamotrigine,
      probably by induction of glucuronidation. A dose increment to 200% of the initial
      lamotrigine dose is needed to achieve concentrations similar to those with
      lamotrigine alone. Lamotrigine does not appear to affect the pharmacokinetics of
      lopinavir/ritonavir.

PMID- 16890576
TI  - Quantitative assessment of seminal vesicle and prostate drug concentrations by
      use of a noninvasive method.
AB  - BACKGROUND: The male genital tract is a complex collection of anatomically and
      biochemically distinct compartments that contribute to the ejaculate.
      Understanding the pharmacokinetics in these compartments should inform rational
      therapeutics involving these glands. METHODS: Nineteen men were administered a
      single dose of 600 mg chloroquine (base) and 975 mg aspirin before providing a
      semen sample by masturbation with fractionation into a 5-compartment collection
      device. Fractions were assayed for fructose (unique seminal vesicle marker),
      prostate-specific antigen (unique prostate marker), salicylate, and chloroquine.
      Seminal vesicle and prostate concentrations of salicylate and chloroquine were
      estimated via a novel analytic method involving a multilevel latent-variable
      model implemented by use of Bayesian methods. RESULTS: The geometric mean
      chloroquine semen/blood ratio was 4.02 (95% confidence interval [CI], 2.36-6.86);
      for salicylate, the primary metabolite of aspirin, the semen/blood ratio was 0.10
      (95% CI, 0.08-0.14). The estimated mean prostate/seminal vesicle ratio for
      salicylate, 0.38 (95% CI by Bayesian methods, 0.12-0.73), was consistent with our
      hypothesis that salicylate would achieve higher concentrations in the seminal
      vesicle than in the prostate. Chloroquine, however, did not demonstrate a
      statistically significant seminal vesicle/prostate difference (4.41; 95% CI by
      Bayesian methods, 0.14-30.52). CONCLUSIONS: We successfully demonstrated the
      quantitative, noninvasive estimation of drug concentrations in the prostate gland
      fluid distinct from the seminal vesicle fluid using our optimized method of split
      ejaculate collection and a novel mixed-effects model with Bayesian estimation.
      Our methods can be applied to gland-specific quantitation of drugs and other
      substances of interest, thus enabling pharmacokinetic, pharmacodynamic, and
      pathophysiologic studies to inform rational therapeutics within different glands
      of the male genital tract.

PMID- 16890578
TI  - VKORC1 gene variations are the major contributors of variation in warfarin dose
      in Japanese patients.
AB  - OBJECTIVES: To compare the genetic and clinical factors that cause large
      interpatient variability and ethnic differences in warfarin efficacy, we
      investigated variations of the VKORC1, CYP2C9, and CYP2C19 genes in Japanese
      subjects. Furthermore, we evaluated the genetic variations and clinical data as
      contributors of variation in warfarin maintenance dose. METHODS: Gene variations
      of VKORC1, CYP2C9, and CYP2C19 in 125 patients treated with warfarin and 114
      healthy subjects were analyzed. The daily dose of warfarin, concentrations of S-
      and R-warfarin in plasma, and prothrombin time expressed as the international
      normalized ratio were used as the pharmacokinetic and pharmacodynamic indices.
      Data were evaluated by a multivariate analysis method. RESULTS: Three missense
      mutations (47 G>C, 113 A>C, and 1338 A>G) in VKORC1 were newly identified in the
      Japanese population. The 113 A>C (Asp38Ser) variant decreased the warfarin dose
      requirement from 3.33 +/- 1.54 mg/d (n = 122) to 1.5 mg/d (n = 1). The variants 
      1639 G>A in the 5'-upstream region, 1173 C>T in intron 1, and 1542 G>C in intron
      2 were in complete linkage disequilibrium, and the frequency of the -1639 G>A
      variation was only 0.8%, which contrasts with the frequency (39.8%-45.8%)
      reported previously for white persons. The dose of warfarin was larger in the
      VKORC1 -1639 GA genotype group (4.55 +/- 1.75 mg/d, P < .001) than in the -1639
      AA group (2.94 +/- 1.15 mg/d). The mean daily dose of warfarin was lower in
      subjects with CYP2C9*1/*3 (1.86 +/- 0.80 mg/d, P = .007) than in subjects with
      CYP2C9*1/*1 (3.36 +/- 1.43 mg/d). When the relative contributions of the VKORC1
      variants, CYP2C9*2, CYP2C9*3, CYP2C19*2, and CYP2C19*3, as well as the clinical
      characteristics of the patients, diagnoses, and concurrent medications, were
      compared, the VKORC1 -1639 GA genotype group accounted for 16.5% and CYP2C9
      variants accounted for 13.4% of variation in warfarin dose. CONCLUSION: The
      ethnic difference in warfarin maintenance dose was mainly dependent on the linked
      VKORC1 variants. Genotyping of -1639 G>A of the VKORC1 gene could be clinically
      important for predicting individual variability in anticoagulant responses to
      warfarin.

PMID- 16890579
TI  - Impact of the haplotype CYP3A4*16B harboring the Thr185Ser substitution on
      paclitaxel metabolism in Japanese patients with cancer.
AB  - OBJECTIVE: Paclitaxel is one of the most important anticancer drugs for the
      treatment of various tumors such as non-small cell lung cancer. We investigated
      the association between CYP3A4 haplotypes and pharmacokinetic parameters of
      paclitaxel metabolism. METHODS: This study enrolled 235 Japanese patients with
      cancer who were receiving paclitaxel. These patients were screened for CYP3A4
      gene polymorphisms by either direct sequencing or pyrosequencing. Plasma
      concentrations of paclitaxel and its 3 metabolites were determined by HPLC in 229
      patients. RESULTS: Median values of paclitaxel clearance, normalized for body
      surface area, were lower in the high-dose group (>or=175 mg/m2, n = 199) than in
      the low-dose group (<or=100 mg/m2, n = 30), suggesting nonlinearity of
      pharmacokinetics caused by Cremophor EL. Therefore we mainly used the patients in
      the high-dose group for further analysis. The median value of the area under the
      curve (AUC) ratio of 3'-p-hydroxypaclitaxel to paclitaxel was 20% greater (95%
      confidence interval, 2.4% to 41.7%) in the women than in the men (P = .01).
      Although no significant difference in paclitaxel clearance was observed among the
      CYP3A4 haplotypes, 16B-bearing (1/16B) patients (n = 8) showed a 20% lower (95%
      confidence interval, -58.5 to -11.5%) median AUC ratio of 3'-p-hydroxypaclitaxel
      to paclitaxel (P = .04) and a 2.4-fold higher median AUC ratio of 6alpha
      hydroxypaclitaxel to paclitaxel (P < .001) compaed with those in the wild-type
      (1/1) patients (n = 180). In contrast, no significant differences were seen
      between 1/1 and 18B/1 (n = 10) patients for the pharmacokinetic parameters
      examined. CONCLUSIONS: Our results suggest that CYP3A416B is associated with both
      reduced 3'-p-hydroxylation of paclitaxel and probably increased levels of 6alpha
      hydroxypaclitaxel.

PMID- 16890581
TI  - Left main coronary artery dissection associated with emotional stress.

PMID- 16890580
TI  - Association of enzyme and transporter genotypes with the pharmacokinetics of
      imatinib.
AB  - OBJECTIVE: Our objective was to explore the relationships between imatinib
      pharmacokinetics and 9 allelic variants in 7 genes coding for adenosine
      triphosphate-binding cassette transporters (ABCB1 and ABCG2) and enzymes
      (cytochrome P450 [CYP] 2C9, CYP2C19, CYP2D6, CYP3A4, and CYP3A5) of putative
      relevance for imatinib. METHODS: Imatinib transport in vitro was studied by use
      of human embryonic kidney 293 cells transfected with wild-type ABCG2 and an ABCG2
      Q141K clone. Steady-state pharmacokinetics of imatinib was obtained in 82
      patients with gastrointestinal stromal tumors treated with oral imatinib at doses
      ranging from 100 to 1000 mg/d. Genotyping was carried out via direct sequencing
      or restriction fragment length polymorphism-based techniques. RESULTS: Human
      embryonic kidney 293 cells transfected with ABCG2 Q141K exhibited greater drug
      accumulation in vitro in comparison with cells expressing wild-type ABCG2 (P =
      .028). However, pharmacokinetic parameters of imatinib in vivo were not
      statistically significantly different in 16 patients who were heterozygous for
      ABCG2 421C>A compared with 66 patients carrying the wild-type sequence (P =
      .479). The apparent oral clearance of imatinib was potentially reduced in
      individuals with at least 1 CYP2D6*4 allele (median, 7.78 versus 10.6 L/h; P =
      .0695). Pharmacokinetic parameters were not related to any of the other multiple
      variant genotypes (P >or= .230), possibly because of the low allele frequencies.
      CONCLUSIONS: This study indicates that common genetic variants in the evaluated
      genes have only a limited impact on the pharmacokinetics of imatinib. Further
      investigation is required to quantitatively assess the clinical significance of
      homozygous variant ABCG2 and CYP2D6 genotypes in patients treated with imatinib.

PMID- 16890588
TI  - Leeuwenhoek meets Kussmaul: the evolution of endoscopist to endo-pathologist.

PMID- 16890589
TI  - Longitudinal change in perceptual and brain activation response to visceral
      stimuli in irritable bowel syndrome patients.
AB  - BACKGROUND & AIMS: Symptom-related fears and associated hypervigilance toward
      visceral stimuli may play a role in central pain amplification and irritable
      bowel syndrome (IBS) pathophysiology. Repeated stimulus exposure leads to
      decreased salience of threat and reduction of hypervigilance. We sought to
      evaluate hypervigilance in IBS visceral hypersensitivity and associated brain
      activity. METHODS: Twenty IBS patients (14 female; moderate to severe symptoms)
      and 14 healthy controls participated in symptom and rectal distention assessments
      6 times over 12 months. In a subset of 12 IBS patients, H2 15O-positron emission
      tomography images were obtained during baseline, rectal distentions, and
      anticipation of an aversive distention during the first and last session.
      Statistical parametric mapping (SPM99) was used to identify areas and networks
      activated during each session as well as those with differential activation
      across the 2 sessions. RESULTS: Perceptual ratings of the rectal inflations
      normalized over 12 months, whereas IBS symptom severity did not. There were no
      sex-related differences in these response patterns. Stable activation of the
      central pain matrix was observed over 12 months, and activity in limbic,
      paralimbic, and pontine regions decreased. During the anticipation condition,
      there were significant decreases in amygdala, dorsal anterior cingulate cortex,
      and dorsal brainstem activation at 12 months. Covariance analysis supported the
      hypothesis of changes in an arousal network including limbic, pontine, and
      cortical areas underlying the decreased perception seen over the multiple
      stimulations. CONCLUSIONS: In IBS patients, repeated exposure to experimental
      aversive visceral stimuli results in the habituation of visceral perception and
      central arousal, despite stable activation of networks processing visceral pain
      and its anticipation.

PMID- 16890590
TI  - Antibodies against laminaribioside and chitobioside are novel serologic markers
      in Crohn's disease.
AB  - BACKGROUND & AIMS: New serologic markers of inflammatory bowel disease may be
      useful for differentiating between Crohn's disease and ulcerative colitis and for
      disease stratification. We profiled sugar-binding antibodies to identify novel
      antiglycan antibodies that may be associated with inflammatory bowel disease.
      METHODS: Serum samples were obtained from patients with diagnosed Crohn's disease
      or ulcerative colitis and from control patients. The presence of antiglycan
      antibodies was evaluated using either a glycan array (GlycoChip; Glycominds, Ltd,
      Lod, Israel) in patients with Crohn's disease (n = 72) or ulcerative colitis (n =
      56) and in healthy controls (n = 41) or using an enzyme-linked immunosorbent
      assay in patients with Crohn's disease (n = 124), ulcerative colitis (n = 106),
      and in control patients (n = 101). RESULTS: Inaddition to antibodies against
      mannan, antibodies to laminaribioside (Glc[beta1,3]Glc[beta]) and chitobioside
      (GlcNAc[beta1,4]GlcNAc[beta]) had the highest discriminative capability between
      Crohn's disease and ulcerative colitis (P < .001 and P < .05, respectively).
      Importantly, 44% (12/27) of anti-Saccharomyces cerevisiae antibody-negative
      Crohn's disease patients were positive for antilaminaribioside or
      antichitobioside. In patients with inflammatory bowel disease positive for
      antibodies against either laminaribioside, chitobioside, or mannan, the diagnosis
      of Crohn's disease was suggested with a sensitivity of 77.4% and specificity of
      90.6%. Having at least 2 of these antibodies increased the specificity to 99.1%.
      In Crohn's disease, higher levels of antibodies against laminaribioside or mannan
      were significantly associated with small intestinal disease (P = .03 and P <
      .0001, respectively). CONCLUSIONS: Antilaminaribioside and antichitobioside
      carbohydrate antibodies are novel serologic markers associated with Crohn's
      disease. These antibodies may contribute to the diagnosis and improved
      stratification of Crohn's disease.

PMID- 16890591
TI  - Laterally spreading type of colorectal adenoma exhibits a unique methylation
      phenotype and K-ras mutations.
AB  - BACKGROUND & AIMS: Laterally spreading tumors (LST), characterized by superficial
      extension along the colonic lumen, have recently been detected by colonoscopy.
      However, genetic and epigenetic characteristics of these tumors were scarcely
      reported. METHODS: A total of 205 sporadic colorectal adenoma tissues (157
      protruded-type, 23 granular-type LST (G-LST), 12 flat-type LST (F-LST), and 13
      flat-type smaller than 1 cm) were collected. CpG island methylator phenotype
      (CIMP) was determined by examination of methylation status at p16, methylated in
      tumor (MINT) 1, 2, 12, and 31 loci. K-ras codon 12 and 13 point mutations were
      also examined. The relationship between macroscopic appearance and CIMP status or
      K-ras mutations was analyzed. RESULTS: Among adenomas larger than 1 cm, CpG
      island methylation involving 2 or more loci (CIMP-high) was more likely to be
      observed in G-LST (14/23, 61%) than in protruded-type adenomas (18/73, 25%) (P =
      .002). The prevalence of K-ras mutations in G-LST (18/23, 78%) was significantly
      higher than that in protruded-type adenomas (18/73, 25%) (P < .0001). Moreover,
      the prevalence of CIMP-high and K-ras mutations in G-LST located in the proximal
      colon was much higher (11/13, 85%; and 12/13, 92%, respectively). In contrast, F
      LST exhibited low prevalence of CIMP-high (1/12, 8%) and K-ras mutations (2/12,
      16%). CONCLUSIONS: High prevalence of CIMP-high and K-ras mutations in G-LST,
      especially in the proximal colon, could strongly suggest that G-LST appearance is
      associated with a unique carcinogenic pathway.

PMID- 16890592
TI  - Limited value of alarm features in the diagnosis of upper gastrointestinal
      malignancy: systematic review and meta-analysis.
AB  - BACKGROUND & AIMS: Alarm features such as dysphagia, weight loss, or anemia raise
      concern of an upper gastrointestinal malignancy in patients with dyspepsia. The
      aim of this study was to determine the diagnostic accuracy of alarm features in
      predicting malignancy by performing a metaanalysis based on the published
      literature. METHODS: English-language studies were identified by searching
      MEDLINE, EMBASE, Cochrane Controlled Trials Register, and CINAHL. Cohort studies
      that measured alarm features and compared them with the endoscopic findings were
      included. Studies were screened for inclusion by 2 authors who independently
      extracted the data. Sensitivity, specificity, and likelihood ratios were
      calculated by comparing the alarm feature with the endoscopic diagnosis. The
      summary receiver operating characteristic curve method was used to summarize test
      characteristics across studies. Individual alarm features were also assessed when
      the study report permitted. RESULTS: Eighty-three of 2600 studies met the initial
      screening criteria; 15 met inclusion criteria after detailed review. These 15
      studies evaluated a total of 57,363 patients, of whom 458 (.8%) had cancer. The
      sensitivity of alarm symptoms varied from 0% to 83% with considerable
      heterogeneity between studies. The specificity also varied significantly from 40%
      to 98%. A clinical diagnosis made by a physician was very specific (range, 97%
      98%) but not very sensitive (range, 11%-53%). CONCLUSIONS: Alarm features have
      limited predictive value for an underlying malignancy. Their use in dyspepsia
      management strategies needs further refinement and study.

PMID- 16890593
TI  - Allergy controls the population density of Necator americanus in the small
      intestine.
AB  - BACKGROUND & AIMS: Nearly 700 million people remain infected with hookworms.
      Although allergy is intuitively linked to immunity against helminths, few
      positive examples have been characterized. Larval migration through the lungs has
      been considered the likely interface at which hookworm attrition occurs. As part
      of a study evaluating a potential role for hookworms in the modulation of human
      autoimmunity, we examined parasite migration and intestinal colonization.
      METHODS: Capsule and conventional endoscopies supplemented the evaluation of
      healthy volunteers and Crohn's disease patients recently inoculated with larvae
      of the human hookworm Necator americanus. Two healthy volunteers with a
      previously established and stable hookworm infection were inoculated with 50
      larvae and had serial capsule endoscopies performed. RESULTS: Eosinophilic
      enteritis developed in all subjects after the initial inoculation. Newly
      inoculated larvae in the 2 subjects with an established infection reliably
      reached the intestine within 4 weeks. Thereafter, the colony diminished to the
      host's constitutive status quo because mostly immature worms failed to attach.
      The intensity of the eosinophilic response correlated negatively with the time
      available for hookworms to feed and positively with hookworm attrition.
      CONCLUSIONS: Necator larval migration to the intestine is uncontested. We propose
      that allergic inflammation purposefully degrades the hookworm's bite, causing
      premature detachment, restricted feeding, and expulsion. This novel biological
      dynamic suggests a new paradigm of hookworm resistance.

PMID- 16890594
TI  - The effect of acute psychologic stress on systemic and rectal mucosal measures of
      inflammation in ulcerative colitis.
AB  - BACKGROUND & AIMS: Recent studies suggest that life events and chronic stress
      increase the risk of relapse in inflammatory bowel disease. Our aim was to study
      the effects of acute psychologic stress on systemic and rectal mucosal
      inflammatory responses in patients with inactive ulcerative colitis (UC).
      METHODS: Twenty-five patients with inactive UC and 11 healthy volunteers (HV)
      underwent an experimental stress test. Ten patients with UC and 11 HV underwent a
      control procedure. Before and after each procedure, systemic inflammatory
      response was assessed by serum interleukin (IL)-6 and IL-13 concentrations, tumor
      necrosis factor (TNF)-alpha and IL-6 production by lipopolysaccharide (LPS)
      stimulated whole blood, leukocyte count, natural killer (NK) cell numbers,
      platelet activation, and platelet-leukocyte aggregate (PLA) formation. In
      patients with UC, rectal mucosal inflammation was assessed by TNF-alpha, IL-13,
      histamine and substance P release, reactive oxygen metabolite (ROM) production,
      mucosal blood flow (RMBF) and histology. RESULTS: Stress increased pulse (P <
      .0001) and systolic BP (P < .0001). In UC, stress increased LPS-stimulated TNF
      alpha and IL-6 production by 54% (P = .004) and 11% (P = .04), respectively,
      leukocyte count by 16% (P = .01), NK cell count by 18% (P = .0008), platelet
      activation by 65% (P < .0001), PLA formation by 25% (P = .004), mucosal TNF-alpha
      release by 102% (P = .03), and ROM production by 475% (P = .001) and reduced
      rectal mucosal blood flow by 22% (P = .05). The control protocol did not change
      any of the variables measured. There were no differences between the responses of
      the patients with UC and HV. CONCLUSIONS: Acute psychologic stress induces
      systemic and mucosal proinflammatory responses, which could contribute to
      exacerbations of UC in ordinary life.

PMID- 16890595
TI  - Adenosine diphosphate ribosyl transferase and x-ray repair cross-complementing 1
      polymorphisms in gastric cardia cancer.
AB  - BACKGROUND & AIMS: Adenosine diphosphate ribosyl transferase (ADPRT) and x-ray
      repair cross-complementing 1 (XRCC1) are major DNA base excision repair proteins
      acting interactively in repair processes. This study examined the effects of
      ADPRT Val762Ala and XRCC1 Arg399Gln polymorphisms on ADPRT-XRCC1 interaction in
      vitro in cells and their contributions to gastric cardia adenocarcinoma (GCA)
      risk. METHODS: The ADPRT-XRCC1 interaction in cells transfected with ADPRT and
      XRCC1 variant complementary DNA (cDNA) constructs were examined by
      immunoprecipitation and immunoblotting analysis. Genotypes were analyzed in 500
      patients and 1000 controls, and odds ratios (ORs) were estimated by logistic
      regression. RESULTS: Interactions between ADPRT-762Val and XRCC1-399Arg or XRCC1
      399Gln were robust, but interactions between ADPRT-762Ala and either XRCC1-399Arg
      or XRCC1-399Gln were very weak. A case-control analysis showed ORs of 2.17 (95%
      CI, 1.55-3.04) and 1.61 (95% CI, 1.06-2.44) for GCA in the ADPRT Ala/Ala or XRCC1
      Gln/Gln genotype carriers, respectively, compared with noncarriers. Gene-gene
      interaction of ADPRT and XRCC1 polymorphisms increased the OR of GCA in a
      multiplicative manner (OR for the presence of both ADPRT Ala/Ala and XRCC1
      Gln/Gln genotypes, 6.43; 95% CI, 1.80-22.97). A supermultiplicative joint effect
      between the ADPRT polymorphism and smoking was observed. The ORs (95% CIs) of the
      Ala/Ala genotype for nonsmokers and smokers who smoked < or = 24 or > 24 pack
      years were 1.44 (0.89-2.32), 2.00 (1.09-3.67), or 3.19 (1.59-6.42), respectively
      (Ptrend test = .008). CONCLUSIONS: The ADPRT and XRCC1 polymorphisms confer host
      susceptibility to GCA, which might result from reduced ADPRT-XRCC1 interaction
      and attenuated base excision repair capacity.

PMID- 16890596
TI  - A unique dendritic cell subset accumulates in the celiac lesion and efficiently
      activates gluten-reactive T cells.
AB  - BACKGROUND & AIMS: Celiac disease is a chronic inflammation of the duodenal
      mucosa driven by gluten-reactive T cells restricted by the disease-associated HLA
      DQ2 molecule. The mechanisms that regulate the activation of mucosal T cells are,
      however, understood poorly. The aim of this study was to identify the antigen
      presenting cells that are responsible for the activation of gluten-reactive T
      cells in the celiac lesion. METHODS: Intestinal biopsy specimens obtained from
      untreated and treated celiac patients and normal controls were either snap-frozen
      directly or incubated for 24 hours with or without gluten peptides. Cryosections
      were subjected to multicolor immunofluorescence applying monoclonal antibodies to
      a range of antigen-presenting cell markers. Macrophages and dendritic cells were
      isolated from enzymatically digested small intestinal biopsies of untreated
      patients and incubated with gluten-reactive T-cell clones to measure their
      antigen-presenting capacity. RESULTS: HLA-DQ2+ cells in the normal duodenal
      mucosa consisted of 2 distinct cell populations: about 80% were CD68+ DC-lysosome
      intercellular adhesion molecule-3-grabbing nonintegrin+ macrophages and 20% were
      CD11c+ dendritic cells. Importantly, the CD11c+ dendritic cells accumulated in
      the celiac lesion and revealed an activated phenotype expressing CD86 and DC
      specific-associated membrane protein. Moreover, when isolated from challenged
      biopsy specimens, the CD11c+ dendritic cells efficiently activated gluten
      reactive T cells. CONCLUSIONS: Our results suggest that a unique subset of
      dendritic cells are responsible for local activation of gluten-reactive T cells
      in the celiac lesion.

PMID- 16890597
TI  - Immunohistochemical expression of MYH protein can be used to identify patients
      with MYH-associated polyposis.
AB  - BACKGROUND & AIMS: MYH-associated polyposis is a recently described, autosomal
      recessive disease characterized by multiple colorectal adenomas and cancer. There
      are only few immunohistochemical studies of the MYH protein. We investigated the
      expression pattern of the MYH protein to evaluate whether a immunohistochemical
      approach could be used in clinical practice to screen patients for germline
      mutations in the MYH gene. METHODS: The expression of MYH, MSH2, MLH1, and MSH6
      proteins was studied by immunohistochemistry in 20 samples (colorectal adenomas
      or cancer) from 18 patients with biallelic MYH mutation, in 11 samples from
      patients with germline adenomatous polyposis coli (APC) mutations, in 20 samples
      from patients with sporadic colorectal cancers, and in 10 samples from patients
      with normal colonic mucosa without malignancies. RESULTS: In all cases the
      mismatch repair proteins were expressed normally. Nuclear and cytoplasmic
      immunoreactivity for the MYH protein were observed in normal colorectal mucosa,
      in sporadic colorectal carcinomas, and in adenomas and carcinomas from patients
      carrying APC germline mutations. Adenomas and carcinomas from patients with MYH
      biallelic mutation showed a different pattern of expression: a strong granular
      cytoplasmic staining was observed without any nuclear expression. The same
      immunophenotype was observed in the surrounding normal mucosa. CONCLUSIONS:
      Patients with biallelic MYH mutations showed disappearance of staining from the
      nucleus, and segregation of immunoreactivity in the cytoplasm, both in neoplastic
      and surrounding healthy mucosa. Because this pattern of expression seems to be
      specific for biallelic mutations, it follows that immunohistochemistry might be
      used in clinical practice to screen patients at risk for MYH-associated
      polyposis.

PMID- 16890598
TI  - Incidence and epidemiology of irritable bowel syndrome after a large waterborne
      outbreak of bacterial dysentery.
AB  - BACKGROUND & AIMS: Postinfectious irritable bowel syndrome (PI-IBS) is a common
      clinical phenomenon. To better define its incidence and epidemiology, a large
      cohort study was initiated after the contamination of a municipal water supply
      led to a large outbreak of acute Escherichia coli 0157:H7 and Campylobacter
      jejuni gastroenteritis. METHODS: Local residents were invited to undergo
      structured assessments at research clinics established 2 years after the
      outbreak. Permanent adult residents with no prior history of inflammatory bowel
      disease or IBS were eligible. Standardized questionnaires defined past and
      current health. The cohort was divided into controls without gastroenteritis,
      subjects with clinically suspected gastroenteritis, and subjects with only self
      reported gastroenteritis that could not be substantiated by another source. A
      modified Bowel Disease Questionnaire identified IBS according to Rome criteria.
      The incidence and epidemiology of PI-IBS was characterized. Risk factors were
      assessed using multiple logistic regression. RESULTS: There were 2069 eligible
      study participants. Rome I criteria were met by 71 of 701 controls (10.1%) vs 249
      of 904 subjects with self-reported gastroenteritis (27.5%) and 168 of 464
      subjects with clinically suspected gastroenteritis (36.2%) (all comparisons, P <
      001). Independent risk factors for PI-IBS included younger age, female sex,
      bloody stools, abdominal cramps, weight loss, and prolonged diarrhea. PI-IBS was
      more likely than sporadic IBS to show diarrhea-predominant features. CONCLUSIONS:
      PI-IBS is common after gastroenteritis from water contamination and often is
      diarrhea-predominant. Characteristics of the acute illness identify patients at
      increased risk for PI-IBS.

PMID- 16890599
TI  - Peginterferon-alfa2a plus ribavirin for 48 versus 72 weeks in patients with
      detectable hepatitis C virus RNA at week 4 of treatment.
AB  - BACKGROUND & AIMS: Patients with chronic hepatitis C who do not respond rapidly
      to therapy have a low chance of developing a sustained virologic response (SVR)
      when treated for 48 weeks. This study investigated whether treatment for 72 weeks
      increases the rate of SVR in patients with detectable hepatitis C virus (HCV)-RNA
      levels at week 4 of treatment. METHODS: A total of 510 treatment-naive patients
      were treated with peginterferon-alfa2a (180 microg/wk) plus ribavirin (800
      mg/day). Patients with detectable HCV-RNA levels at week 4 (n = 326) were
      randomized to complete 48 (group A, n = 165) or 72 weeks (group B, n = 161) of
      treatment. Patients with undetectable HCV-RNA levels at week 4 (n = 184) were
      allocated into group C (n = 148) or group D (n = 36), according to HCV genotype
      and baseline viremia, and treated for 24 or 48 weeks, respectively. All patients
      were followed-up for 24 weeks after the end of treatment. RESULTS: The end-of
      treatment response rate (61%) was similar in groups A and B, but the SVR rate was
      higher in group B (45% vs 32% in A; P = .01). In genotype 1-infected patients
      randomized to group A (n = 149) or B (n = 142), SVR rates were 28% and 44%,
      respectively (P = .003). The incidence of adverse events was similar in all
      groups. Treatment discontinuation was more frequent in group B (36%) than in
      group A (18%) (P = .0004). SVR rates in groups C and D were 79% and 64%,
      respectively. CONCLUSIONS: Extension of treatment with peginterferon-alfa2a plus
      ribavirin from 48 to 72 weeks significantly increases the rate of SVR in patients
      with detectable viremia at week 4 of treatment.

PMID- 16890600
TI  - Prospective cohort study of transarterial chemoembolization for unresectable
      hepatocellular carcinoma in 8510 patients.
AB  - BACKGROUND & AIMS: To elucidate the survival of the patients with unresectable
      hepatocellular carcinoma (HCC) who underwent transcatheter arterial lipiodol
      chemoembolization (TACE) and to analyze the factors affecting the survivals.
      METHODS: During the last 8 years, a nationwide prospective cohort study was
      performed in 8510 patients with unresectable HCC who underwent TACE using
      emulsion of lipiodol and anticancer agents followed by gelatin sponge particles
      as an initial treatment. Exclusion criteria were extrahepatic metastases and/or
      any previous treatment prior to the present TACE. The primary end point was
      survival. The survival rates were calculated by the Kaplan-Meier method. The
      multivariate analyses for the factors affecting survival were evaluated by the
      Cox proportional hazard model. The mean follow-up period was 1.77 years. RESULTS:
      For overall survival rates by TACE, median and 1-, 3-, 5-, and 7-year survivals
      were 34 months, 82%, 47%, 26%, and 16%, respectively. Both the degree of liver
      damage and the tumor-node-metastasis (TNM) system proposed by the Liver Cancer
      Study Group of Japan demonstrated good stratification of survivals (P = .0001).
      The multivariate analyses showed significant difference in degree of liver damage
      (P = .0001), alpha-fetoprotein value (P = .0001), maximum tumor size (P = .0001),
      number of lesions (P = .0001), and portal vein invasion (P = .0001). The last 3
      factors could be replaced by TNM stage. The TACE-related mortality rate after the
      initial therapy was .5%. CONCLUSIONS: TACE showed safe therapeutic modality with
      a 5-year survival of 26% for unresectable HCC patients. The degrees of liver
      damage, TNM stage, and alpha-fetoprotein values were independent risk factors for
      patient survival.

PMID- 16890601
TI  - Peginterferon and ribavirin treatment in African American and Caucasian American
      patients with hepatitis C genotype 1.
AB  - BACKGROUND & AIMS: Compared with Caucasian Americans (CA), African Americans (AA)
      with chronic hepatitis C are less likely to respond to interferon-based antiviral
      therapy. METHODS: In a multicenter treatment trial, 196 AA and 205 CA treatment
      naive patients with hepatitis C virus (HCV) genotype 1 infection were treated
      with peginterferon alfa-2a (180 microg/wk) and ribavirin (1000-1200 mg/day) for
      up to 48 weeks. The primary end point was sustained virologic response (SVR).
      RESULTS: Baseline features were similar among AA and CA, including HCV-RNA levels
      and histologic severity, but AA had higher body weights, a higher prevalence of
      diabetes and hypertension, and lower alanine transaminase levels (P < .001 for
      all). The SVR rate was 28% in AA and 52% in CA (P < .0001). Racial differences in
      viral responses were evident as early as treatment week 4. Breakthrough viremia
      was more frequent among AA than CA (13% vs 6%, P = .05); relapse rates were
      comparable (32% vs 25%, P = .30). Proportions of patients with serious adverse
      events and dose modifications and discontinuations were similar among AA and CA.
      In multiple regression analyses, CA had a higher SVR rate than AA (relative risk,
      1.96; 95% confidence interval, 1.48-2.60; P < .0001). Other factors independently
      associated with higher SVR included female sex, lower baseline HCV-RNA level,
      less hepatic fibrosis, and more peginterferon taken. CONCLUSIONS: AA with chronic
      hepatitis C genotype 1 have lower rates of virologic response to peginterferon
      and ribavirin than CA. These differences are not explained by disease
      characteristics, baseline viral levels, or amount of medication taken.

PMID- 16890602
TI  - Hepatitis C virus genotypes and viral concentrations in participants of a general
      population survey in the United States.
AB  - BACKGROUND & AIMS: Estimates of the long-term benefits of antiviral therapies for
      chronic hepatitis C are influenced by the frequency of characteristics that
      affect response in the population treated. This study determined hepatitis C
      virus (HCV) genotypes and RNA titers among HCV-infected persons in the general
      population of the United States. METHODS: Genotypes were determined from the NS5b
      region, and HCV RNA was quantified by using Amplicor Monitor (Roche Diagnostic
      Systems, Inc, Branchburg, NJ) from 275 HCV RNA-positive participants in the Third
      National Health and Nutrition Examination Survey conducted during 1988 to 1994.
      RESULTS: The HCV genotypes identified included 1a (n = 142), 1b (n = 73), 2a (n =
      8), 2b (n = 27), 3a (n = 17), 4 (n = 3), and 6 (n = 5). Based on weighted
      analysis of persons infected with genotypes 1, 2, and 3, genotype 1 predominated
      in all age groups (75.3%). By racial/ethnic group, genotype 1 was found in 90.9%
      of non-Hispanic blacks, 69.6% of non-Hispanic whites, and 71.2% of Mexican
      Americans. After adjusting for age and gender, only non-Hispanic black
      race/ethnicity was independently associated with genotype 1 infection (adjusted
      odds ratio 4.9; 95% confidence interval, 1.9-12.8). The overall geometric mean
      concentration of HCV RNA was 2.1 x 10(6) IU/mL; concentrations > 2 million IU/mL
      were found in 53.0% overall and 50.3% of persons with genotype 1. CONCLUSIONS:
      Persons with chronic hepatitis C in the United States who may require treatment
      in the foreseeable future are predominantly infected with genotype 1, including a
      disproportionate number of non-Hispanic blacks. These features emphasize the need
      for improved therapies that reduce or eliminate complications from genotype 1
      infections.

PMID- 16890603
TI  - CD8+ cytotoxic T cells induce relapsing colitis in normal mice.
AB  - BACKGROUND & AIMS: Most mouse models of IBD have emphasized an effector role of
      type-1 CD4+ T cells in colitis. The aim of this study was to develop a model of
      antigen-specific relapsing colitis to investigate the relative contribution of
      CD4+ and CD8+ effectors. METHODS: Balb/C mice were sensitized and challenged with
      a suboptimal dose of 2.4 dinitrobenzene sulfonic acid to generate a colonic
      delayed-type hypersensitivity response. The respective role of CD4+ and CD8+ T
      cells in the initiation of colitis was analyzed by in vivo monoclonal antibody
      depletion and cell-transfer experiments. Dynamic and function of the colitogenic
      effectors were studied by immunohistochemistry, fluorescence-activated cell
      sorter analysis, enzyme-linked immunospot assay, quantitative polymerase chain
      reaction, and in vivo CTL assays. RESULTS: Relapsing colitis rapidly occurred
      only after challenge of previously sensitized mice. Interferon-gamma-producing
      cytotoxic CD8+ T cells (Tc1) specific for hapten-modified self-proteins were
      generated in colon-draining lymph nodes on day 5 after sensitization, before the
      onset of disease. These CD8+ T cells were rapidly recruited upon challenge into
      colon lamina propria as granzyme B-expressing effectors exerting ex vivo
      cytotoxicity against syngeneic hapten-modified colonic epithelial cells. Colitis
      was prevented by in vivo antibody depletion of CD8+, but not of CD4+, T cells and
      could be induced in naive recipients within 48 hours after transfer of CD8+, but
      not CD4+, T cells purified from sensitized mice. CONCLUSIONS: Our data show that
      antigen-specific CD8+ T cells can induce relapsing colitis in normal mice and
      suggest that the cytolytic function of CD8 Tc1 against epithelial cells may
      initiate the intestinal inflammatory process.

PMID- 16890604
TI  - The role of tumor necrosis factor alpha in down-regulation of osteoblast Phex
      gene expression in experimental murine colitis.
AB  - BACKGROUND & AIMS: Reduced bone mass is a common complication of inflammatory
      bowel disease (IBD), although the mechanisms that contribute to osteopenia are
      not completely understood. Tumor necrosis factor alpha (TNF-alpha) is up
      regulated in patients with IBD and has detrimental effects on osteoblasts. Phex
      gene is expressed predominantly in osteoblasts, and its disruption results in
      defective bone mineralization. The aim of this study was to evaluate whether TNF
      alpha regulates Phex gene expression thus contributing to the abnormal bone
      metabolism observed in IBD. METHODS: Phex gene expression was evaluated in
      calvaria of 6-7-week-old mice administered with trinitrobenzene sulfonic acid
      (TNBS) with or without neutralizing anti-TNF-alpha antibody, dietary curcumin, or
      systemically with recombinant TNF-alpha. TNF-alpha-treated UMR-106 osteoblasts
      were also examined. Phex promoter activity was assayed in transiently transfected
      TNF-alpha-treated UMR-106 cells. RESULTS: Compared with control animals, Phex
      messenger RNA (mRNA) expression decreased by 40%-50% in both TNBS colitis and TNF
      alpha-injected mice. Dietary curcumin and anti-TNF-alpha antibody counteracted
      the detrimental effect of TNBS on Phex gene expression. TNF-alpha-treated UMR-106
      cells showed a concentration-dependent and transcriptionally mediated decrease in
      Phex mRNA and gene promoter activity, with the -133 to -74 bp region of the Phex
      promoter likely involved in the mechanism of TNF-alpha action. Coinciding with
      decreased Phex protein level, TNF-alpha drastically reduced mineralization in UMR
      106 osteoblasts. CONCLUSIONS: Acute colitis and TNF-alpha decrease Phex mRNA and
      protein expression via a transcriptional mechanism. TNF-alpha-mediated reduction
      in Phex protein is at least in part responsible for inhibition of osteoblast
      mineralization, and the described mechanism may contribute to the abnormal bone
      metabolism associated with IBD.

PMID- 16890605
TI  - Autoimmune-mediated intestinal inflammation-impact and regulation of antigen
      specific CD8+ T cells.
AB  - BACKGROUND & AIMS: Few data exist regarding mechanisms of mucosal CD8+ T-cell
      reactivity to epithelial-specific antigen. To dissect the immunologic mechanisms
      underlying CD8+ T-cell dysregulation, reactivity to a self-antigen expressed in
      intestinal epithelium of mice bearing a major histocompatibility complex class I
      restricted T-cell receptor specific for this antigen was studied. In addition,
      antigen-specific regulatory CD4+ T cells induced in vivo were tested to control
      these autoreactive CD8+ T cells. METHODS: Transgenic VILLIN-HA mice were mated
      with CL4-TCR transgenic mice. Alternatively, adoptive transfer of CL4-TCR
      transgenic CD8+ T cells into VILLIN-HA transgenic mice was performed to mimic
      spontaneous encounter of neoantigen. Mucosal CD8+ T cells were characterized
      under different conditions of tolerance, immunopathology, and active
      immunosuppression. RESULTS: Transgenic CD8+ T cells from VILLIN-HA x CL4-TCR
      transgenic mice preferentially migrated and expanded in mucosal lymphoid tissues.
      Although transgenic CD8+ T cells showed signs of T-cell activation, they failed
      to cause tissue damage. This was accompanied by the induction/expansion of CD4+
      and CD8+, Foxp3-expressing T cells. In contrast, adoptive transfer of naive
      transgenic CD8+ T cells from CL4-TCR transgenic mice into VILLIN-HA transgenic
      mice induced severe intestinal inflammation with poor clinical course of disease.
      Transgenic CD8+ T cells secreted vigorous amounts of proinflammatory cytokines
      like interferon gamma/tumor necrosis factor alpha. Strikingly, this acute wasting
      disease was significantly ameliorated by cotransfer of antigen-specific
      regulatory CD4+ T cells. CONCLUSIONS: Epithelial-specific antigen expression is
      sufficient to trigger severe antigen-specific CD8+ T-cell-mediated intestinal
      inflammation; this might be controlled by antigen-specific regulatory T cells
      under physiological conditions.

PMID- 16890606
TI  - CD25+/Foxp3+ T cells regulate gastric inflammation and Helicobacter pylori
      colonization in vivo.
AB  - BACKGROUND & AIMS: Helicobacter pylori infects more than half of the world's
      population. In contrast to most other pathogens, the microbe persists for the
      virtual life of its host. It is unclear why the immune system is unable to
      eliminate the infection, but recent studies suggested that CD4+/CD25+/Foxp3+
      regulatory T cells may be involved in this process. METHODS: By using a mouse
      model of infection and gastric biopsies from 108 patients, we performed a
      detailed descriptive and functional characterization of the Helicobacter-induced
      CD25+/Foxp3+ T-cell response. RESULTS: In C57BL/6 mice, H pylori induced a marked
      gastric Foxp3+ T-cell response, which increased over several months together with
      the severity of inflammation, until a stable homeostatic situation became
      established. Accordingly, in Helicobacter-infected patients, but not in
      uninfected individuals, large numbers of gastric Foxp3+ T cells were detected
      immunohistochemically. To define the functional in vivo relevance of this
      response, CD25+ cells were depleted systemically in mice by using an anti-CD25
      monoclonal antibody (PC61). Already 4 weeks after infection, PC61-treated mice,
      but not untreated animals, developed a severe gastritis with heightened cytokine
      expression and increased numbers of mucosal T cells, B cells, and macrophages.
      This was accompanied by increased titers of H pylori-specific IgG1 and IgG2c
      antibodies in the sera of PC61-treated mice. This increased gastric inflammatory
      response in CD25-depleted mice was associated with reduced bacterial loads.
      CONCLUSIONS: CD25+/Foxp3+ T cells actively participate in the immune response to
      H pylori. In vivo depletion of these cells in infected mice leads to increased
      gastric inflammation and reduced bacterial colonization.

PMID- 16890607
TI  - PPARbeta/delta regulates paneth cell differentiation via controlling the hedgehog
      signaling pathway.
AB  - BACKGROUND & AIMS: All 4 differentiated epithelial cell types found in the
      intestinal epithelium derive from the intestinal epithelial stem cells present in
      the crypt unit, in a process whose molecular clues are intensely scrutinized.
      Peroxisome proliferator-activated receptor beta (PPARbeta) is a nuclear hormone
      receptor activated by fatty acids and is highly expressed in the digestive tract.
      However, its function in intestinal epithelium homeostasis is understood poorly.
      METHODS: To assess the role of PPARbeta in the small intestinal epithelium, we
      combined various cellular and molecular approaches in wild-type and PPARbeta
      mutant mice. RESULTS: We show that the expression of PPARbeta is particularly
      remarkable at the bottom of the crypt of the small intestine where Paneth cells
      reside. These cells, which have an important role in the innate immunity, are
      strikingly affected in PPARbeta-null mice. We then show that Indian hedgehog
      (Ihh) is a signal sent by mature Paneth cells to their precursors, negatively
      regulating their differentiation. Importantly, PPARbeta acts on Paneth cell
      homeostasis by down-regulating the expression of Ihh, an effect that can be
      mimicked by cyclopamine, a known inhibitor of the hedgehog signaling pathway.
      CONCLUSIONS: We unraveled the Ihh-dependent regulatory loop that controls mature
      Paneth cell homeostasis and its modulation by PPARbeta. PPARbeta currently is
      being assessed as a drug target for metabolic diseases; these results reveal some
      important clues with respect to the signals controlling epithelial cell fate in
      the small intestine.

PMID- 16890608
TI  - c-Fos is a critical mediator of inflammatory-mediated repression of the apical
      sodium-dependent bile acid transporter.
AB  - BACKGROUND & AIMS: Ileal bile acid malabsorption is present in Crohn's ileitis.
      The molecular mechanisms of regulation of the apical sodium-dependent bile acid
      transporter (ASBT) by inflammatory cytokines in vitro and in vivo are
      investigated. METHODS: Transient transfection studies of the human, mouse, and
      rat ASBT promoters and Northern analyses were performed in cells treated with the
      inflammatory cytokines and/or various activator protein-1 constructs. Rat ASBT
      promoter transgenic, wild-type, and c-fos-null mice were treated with
      indomethacin to assess the response to acute inflammation of the ileal mucosa.
      RESULTS: In Caco-2 cells, ASBT messenger RNA expression was reduced 65% after
      interleukin-1beta treatment, while c-fos and c-jun were up-regulated 2-fold.
      Human ASBT promoter activity was enhanced by c-jun and repressed by a dominant
      negative c-jun, c-fos, or a dominant negative c-fos. Meanwhile, c-fos antisense
      treatment activated the human ASBT promoter 5-fold and not only abrogated
      interleukin-1beta-mediated repression but led to a paradoxical increase in ASBT
      promoter activity. Indomethacin-induced acute ileitis led to repression of ASBT
      in wild-type mice and in the transgenic rat ASBT promoter reporter, while
      paradoxical activation of ASBT was seen in c-fos-null mice. Indomethacin-induced
      ileal injury was greater in the c-fos-null mice compared with the wild-type
      littermates. CONCLUSIONS: Human, rat, and mouse ASBT is inhibited by inflammatory
      cytokines via direct interactions of c-fos with the ASBT promoter.

PMID- 16890609
TI  - Contribution of 5-HT2A receptor in nematode infection-induced murine intestinal
      smooth muscle hypercontractility.
AB  - BACKGROUND & AIMS: Enteric nematode infection induces a smooth muscle
      hypercontractility that depends on interleukin (IL)-4 and IL-13 activation of the
      signal transducer and activator of transcription (STAT) 6. Serotonin (5-HT) is
      involved in the physiologic regulation of gut function. The present study
      investigated the contribution of 5-HT and its receptors in nematode-induced
      intestinal smooth muscle hypercontractility. METHODS: Mice were infected with
      Nippostrongylus brasiliensis (N brasiliensis) or Heligmosomoides polygyrus (H
      polygyrus) or injected intravenously with IL-13. Segments of jejunum were
      suspended in organ baths, and smooth muscle responses to 5-HT were determined in
      the presence or absence of specific 5-HT antagonists. IL-4, IL-13, and 5-HT
      receptor messenger RNA expressions were determined by real-time quantitative
      polymerase chain reaction. RESULTS: 5-HT evoked a modest contraction of smooth
      muscle in wild-type (WT) mice that was unaltered by the 5-HT2A antagonist
      ketanserin. N brasiliensis infection induced a smooth muscle hypercontractility
      to 5-HT that was abolished by 5-HT(2A) antagonists but not by other 5-HT
      antagonists. Infection-induced up-regulation of 5-HT2A expression was correlated
      with the smooth muscle hypercontractility to 5-HT. The infection-induced up
      regulation of 5-HT2A in WT mice was observed also in IL-4(-/-) mice but was not
      seen in IL-13(-/-) or STAT6(-/-) mice. In addition, smooth muscle responses to 5
      HT and 5-HT2A expression in WT mice were also enhanced by IL-13 or H polygyrus
      infection. CONCLUSIONS: These data show that 5-HT2A is one of the molecules
      downstream from STAT6 activation that mediates changes in smooth muscle function.
      5-HT2A represents a novel therapeutic target for modulating immune-mediated
      effects on intestinal motility.

PMID- 16890610
TI  - Deletion of Mtgr1 sensitizes the colonic epithelium to dextran sodium sulfate
      induced colitis.
AB  - BACKGROUND & AIMS: The disruption of homeostasis between proliferation and
      apoptosis in the colonic epithelium contributes to the pathogenesis of human
      ulcerative colitis. Mice lacking the transcriptional corepressor myeloid
      translocation gene related-1 (Mtgr1) display impaired secretory cell lineage
      development in the small intestine and an increase in proliferation in the crypts
      of both the small and large intestines. Despite the increase in proliferating
      cells, the colons of Mtgr1-null mice have a normal cell lineage distribution and
      normal architecture. To uncover colonic phenotypes in Mtgr1(-/-) mice, we
      stressed the colonic epithelium with low-molecular-weight dextran sodium sulfate
      (DSS), which is a well-studied model of murine ulcerative colitis. METHODS: Mtgr1
      null mice were given 3% DSS in their drinking water for 4 days and the colons
      examined at various times thereafter for ulceration and for changes in
      proliferation and apoptosis. RESULTS: Treatment with DSS resulted in severe
      colitis in Mtgr1(-/-) mice, at least partially due to increased epithelial
      apoptosis rates. Transplantation of wild-type and Mtgr1-null bone marrow into
      irradiated wild-type mice demonstrated that the severe DSS-induced ulceration
      seen in Mtgr1-null mice was due to a colonic, rather than a hematologic, defect.
      Importantly, the epithelium of DSS-treated Mtgr1-null mice failed to completely
      regenerate, showing changes consistent with chronic colitis, even 10 weeks after
      a single DSS treatment. CONCLUSIONS: These findings suggest that Mtgr1 has an
      important role in crypt survival and regeneration after colonic epithelial
      ulceration.

PMID- 16890611
TI  - The essential role of insulin-like growth factor-1 in the intestinal tropic
      effects of glucagon-like peptide-2 in mice.
AB  - BACKGROUND & AIMS: Glucagon-like peptide-2 (GLP-2) is an intestinal hormone that
      acts through unknown pathways to induce intestinal growth. We investigated the
      role of the insulin-like growth factors (IGF-1 and IGF-2) as mediators of GLP-2
      enhanced growth in the murine intestine. METHODS: IGF-1 expression and secretion
      were determined in GLP-2-responsive primary intestinal cultures treated with GLP
      2. Parameters of intestinal growth were assessed in wild-type (CD1, Igf1(+/+) and
      Igf2+), heterozygous (Igf1(+/-)), and null (Igf1(-/-) and Igf2(-P)) mice treated
      chronically with saline, GLP-2, IGF-1, or R-Spondin1. RESULTS: GLP-2 increased
      IGF-1 messenger RNA expression and IGF-1 secretion in intestinal cultures and
      increased expression of IGF-1 messenger RNA in mouse small intestine in vivo.
      Igf1(+/+) and Igf2+ mice responded to .1 microg/g(-1) per day(-1) GLP-2 with
      increased intestinal weights, morphometric parameters, and proliferative indices.
      In contrast, Igf1(-/-) mice were unresponsive to the same dose of GLP-2, failing
      to demonstrate changes in intestinal weight, morphometry, or proliferation.
      However, a significant effect of 1 microg/g(-1) per day(-1) GLP-2 was observed in
      Igf1(-/-) mice, but only in terms of small intestinal weight when normalized for
      body weight. Furthermore, Igf2(-P) mice demonstrated a partially impaired
      response in terms of small intestinal growth. Both Igf1(-/-) and Igf2(-P) mice
      exhibited normal-enhanced intestinal growth in response to IGF-1 and/or R
      Spondin1. CONCLUSIONS: GLP-2 enhances intestinal IGF-1 expression and secretion,
      and IGF-1 is required for small and large intestinal growth in response to GLP-2.
      These findings identify IGF-1 as an essential mediator of the intestinotropic
      actions of GLP-2.

PMID- 16890612
TI  - Autoreactive T-cell responses in primary biliary cirrhosis are proinflammatory
      whereas those of controls are regulatory.
AB  - BACKGROUND & AIMS: Autoreactive T cells that proliferate in response to
      autoantigens are found in both autoimmune disease and controls but have important
      qualitative differences in relative activation states, costimulation signal
      requirements, and pathogenetic significance. Understanding the mechanism for
      activation of autoreactive T cells will be critical in the treatment of
      autoimmune diseases. METHODS: To understand the differences between autoreactive
      T cells in primary biliary cirrhosis (PBC) versus controls, we have developed
      autoreactive T-cell clones (TCCs) from patients with PBC and healthy controls and
      have used a peptide corresponding to the CD4 major autoepitope to define the
      relative proliferative and cytokine response. RESULTS: Using an enzyme-linked
      immunosorbent spot assay, peripheral blood mononuclear cells (PBMCs) from PBC,
      but not from controls, produce interferon (IFN)-gamma regardless of whether
      costimulation-competent or -incompetent antigen-presenting cells (APC) were used.
      In contrast, a significant number of IFN-gamma-producing cells were found in
      PBMCs from controls but only if costimulation-competent PBMCs presented an
      autoantigenic peptide. In addition, costimulation-dependent autoreactive TCCs
      became anergic after a single round of stimulation in the presence of APC that
      did not provide a costimulatory signal, whereas some costimulation-independent
      autoreactive TCCs required repeated stimulation to become anergic and the others
      did not become anergic. Finally, anergic TCCs produced interleukin-10, but no IFN
      gamma, and exhibited regulatory functions in an antigen-dependent, cell contact
      independent, and partially interleukin-10-mediated manner. CONCLUSIONS: These
      data relate specifically to the functional characteristics of autoreactive T
      cells in PBC but are also generically important for understanding the mechanisms
      for generating pathogenetic autoreactive T cells.

PMID- 16890613
TI  - Asymptomatic liver mass.

PMID- 16890614
TI  - Combined mutations of canalicular transporter proteins cause severe intrahepatic
      cholestasis of pregnancy.
AB  - Intrahepatic cholestasis of pregnancy (ICP) is a cholestatic disorder that
      usually develops in the third trimester of pregnancy and persists until delivery.
      The cause of ICP remains elusive, but there is evidence that mutations in the
      canalicular ABC transporter phospholipid flippase (MDR3) and in the bile salt
      export pump (BSEP) can predispose for the development of ICP. MDR3 and BSEP were
      investigated by gene sequencing and immunofluorescence microscopy in a patient
      with severe ICP of early onset. ICP was diagnosed in a patient in the first
      trimester of pregnancy with severe pruritus, elevated levels of bile salts, and
      48-fold elevation of transaminase levels. A liver biopsy specimen showed
      diminished canalicular expression of the bile salt export pump BSEP, while the
      expression and localization of the phospholipid flippase MDR3 was normal. Gene
      sequencing revealed a homozygous MDR3 gene mutation (S320F). The patient was also
      homozygous for the common BSEP polymorphism V444A. Treatment with
      ursodeoxycholate normalized transaminase levels but could not prevent further
      elevation of bile salt levels and preterm delivery. The combined homozygous
      alterations of the canalicular transporters may explain the early onset and
      severity of ICP in this patient. The common BSEP polymorphism V444A accounts for
      the reduced canalicular BSEP expression. Reduced bile salt secretion through BSEP
      may explain the persistence of elevated bile salt levels and incomplete efficacy
      of ursodeoxycholate treatment.

PMID- 16890615
TI  - CD24 is a new oncogene, early at the multistep process of colorectal cancer
      carcinogenesis.
AB  - BACKGROUND & AIMS: The aim of this study was to identify genes that play a role
      in colorectal cancer (CRC) carcinogenesis by analysis of differential gene
      expression of normal and transformed CRC cell lines. METHODS: Gene expression
      array analysis ([RG-U34] GeneChip) was performed in normal and transformed rat
      intestinal epithelial cells before and after exposures to celecoxib. In
      particular, we were looking for (1) altered gene expression in the transformed
      cells that reverts to normal following exposure to a selective cyclooxygenase-2
      inhibitor, (2) novel genes, and (3) genes encoding membrane receptors or ligands.
      As a validation of the results and for human patients, immunohistochemistry was
      performed on 398 biological samples from the gastrointestinal tract (normal,
      polyps, and adenocarcinomas). Human cancer cell lines were tested for their
      response to anti-CD24 monoclonal antibodies. RESULTS: A total of 1081 genes were
      differently expressed following malignant transformation; 71 genes showed altered
      expression that reverted to normal following treatment with celecoxib, including
      the CD24 gene. Immunohistochemistry confirmed that increased expression of CD24
      is an early event in CRC carcinogenesis. It was expressed in 90.7% of adenomas
      and 86.3% of CRCs. Very low expression was seen in normal epithelium (16.6%).
      Human cancer cell lines showed growth inhibition in response to the antibodies,
      according to their expression levels of CD24 and in dose- and time-dependent
      manners. These results were repetitive for 3 different antibodies. CONCLUSIONS:
      CD24 is overexpressed in the colonic mucosa, already at an early stage of
      carcinogenesis. It may be a useful target for early detection and in CRC therapy.

PMID- 16890616
TI  - Integrated upper gastrointestinal response to food intake.

PMID- 16890617
TI  - Visceral hypersensitivity: fact or fiction.

PMID- 16890618
TI  - Serologies in Crohn's disease: can we change the gray zone to black and white?

PMID- 16890619
TI  - In IBD eight can come before four.

PMID- 16890620
TI  - Budd-Chiari Syndrome: a clinical model of the hepatorenal reflex?

PMID- 16890621
TI  - Ecological diversity measures predict cancer progression in Barrett's esophagus.

PMID- 16890623
TI  - Multicenter timolol study: the value of timolol and hemodynamic monitoring in the
      management of portal hypertensive cirrhotics with no esophageal varices.

PMID- 16890624
TI  - Drinker's pancreas and abnormal diffusion-weighted MR: what's the connection?

PMID- 16890626
TI  - Snack time.

PMID- 16890627
TI  - Treatment of acute hepatitis C-how to explain the differences?

PMID- 16890631
TI  - The risk of colorectal cancer in ulcerative colitis in a population-based
      setting.

PMID- 16890628
TI  - Peginterferon alfa-2b therapy in acute hepatitis C: impact of onset of therapy on
      sustained virologic response.

PMID- 16890632
TI  - Hepatitis C infection and lymphomas: is there any benefit in viral treatment?

PMID- 16890638
TI  - We need to lead and not be led.

PMID- 16890639
TI  - Combined metabolic/anatomical imaging in urologic oncology.

PMID- 16890640
TI  - Bladder cancer prevention--could a carrot be the stick?

PMID- 16890641
TI  - Management of adult ureteropelvic junction obstruction--is it time for a new gold
      standard?

PMID- 16890642
TI  - The interpretation of serum prostate specific antigen in men receiving 5alpha
      reductase inhibitors: a review and clinical recommendations.
AB  - PURPOSE: We reviewed the effects of 5alpha-reductase inhibitors on prostate
      specific antigen and clarified the adjustments that should be made to compensate
      for these effects to ensure that the usefulness of prostate specific antigen for
      detecting prostate cancer is maintained. MATERIALS AND METHODS: We reviewed
      articles published in the scientific literature with relevance to the effects of
      5alpha-reductase inhibitors on the usefulness of prostate specific antigen for
      detecting prostate cancer. RESULTS: A total serum prostate specific antigen of
      4.0 ng/ml has traditionally been used as the threshold for triggering prostate
      biopsy. However, clinical trials of finasteride and dutasteride have shown that
      5alpha-reductase inhibitors decrease serum prostate specific antigen in patients
      with and without prostate cancer. To compensate, the doubling rule has been
      applied in clinical trials and clinical practice. However, doubling serum
      prostate specific antigen may overestimate actual prostate specific antigen in
      some patients receiving 5alpha-reductase inhibitors for up to 6 to 9 months,
      accurately estimate prostate specific antigen from 1 to 3 years and underestimate
      it thereafter. An increase in prostate specific antigen of 0.3 ng/ml from nadir
      as a trigger for biopsy maintains 71% sensitivity for prostate cancer in men
      receiving dutasteride with 60% specificity, similar to the 4.0 ng/ml prostate
      specific antigen cutoff using placebo. CONCLUSIONS: We propose that a prostate
      specific antigen increase from nadir of 0.3 ng/ml or greater could represent an
      alternative to the doubling rule for monitoring prostate specific antigen in
      patients on 5alpha-reductase inhibitors. The prostate specific antigen increase
      from nadir appears to be a more accurate cancer indicator than a doubled value in
      some patients.

PMID- 16890643
TI  - Testicular and paratesticular neoplasms in prepubertal males.
AB  - PURPOSE: We reviewed the current diagnosis, staging and management of testicular
      and paratesticular neoplasms in prepubertal males. MATERIALS AND METHODS: We
      performed a medical literature search in English using MEDLINE/PubMed that
      addressed testicular and/or paratesticular neoplasms in prepubertal males. We
      then analyzed the literature with respect to individual tumors. We present a
      concise approach toward the management of these individual tumors. RESULTS: There
      is still a predominance of yolk sac tumors in prepubertal males, although some
      studies suggest that teratomas are more common but underreported due to their
      benign course in children. Prepubertal males are diagnosed in a fashion similar
      to that in adult patients with an appropriate history and physical examination. A
      palpable, nontender mass suggests the diagnosis and prompts scrotal ultrasound
      and tumor markers. Although treatment for most primary tumors has historically
      been radical inguinal orchiectomy, most benign tumors can now be managed by
      testis sparing surgery. The addition of radiation, chemotherapy and/or
      retroperitoneal lymph node dissection depends on tumor stage and histological
      type. CONCLUSIONS: Although it is rare in children, any solid scrotal mass in
      prepubertal males warrants evaluation for possible testicular or paratesticular
      neoplasm.

PMID- 16890645
TI  - The first human renal transplants.

PMID- 16890644
TI  - Neuromodulatory therapy to improve erectile function recovery outcomes after
      pelvic surgery.
AB  - PURPOSE: Erectile dysfunction is a recognized, common adverse consequence of
      radical prostatectomy as well as various other pelvic surgeries. While a host of
      management options have been considered to decrease this complication,
      neuromodulatory therapy has recently been advanced as an intervention that may be
      applied for this purpose. We evaluated concepts regarding the neuropathic basis
      for erectile dysfunction following pelvic surgery, principles for establishing
      neuromodulatory therapy in this clinical context, evidence from preclinical
      studies supporting neuromodulatory approaches as a therapeutic strategy and the
      progress of early clinical developments in this field. MATERIALS AND METHODS: The
      exercise principally consisted of a current literature search using the National
      Library of Medicine PubMed Services, a survey of recent abstract proceedings from
      national meetings relevant to the topic and an Internet online search for current
      information on federally and privately supported clinical trials specific to this
      topic. References were made to such key words as neuroprotection, nerve
      regeneration, nerve growth factors, neurotrophic factors, cavernous nerves, nerve
      guides and penile erection. RESULTS: Basic science research and clinical studies
      support the concept that erectile loss after pelvic surgery is frequently related
      to neuropathic effects, resulting in penile vascular impairment. An assortment of
      neurobiological studies using rodent models of cavernous nerve injury have shown
      nerve reconstitutive actions for a host of neurotrophic substances, including
      classic neurotrophins, growth hormone, cytokines and atypical neurotrophic
      mediators. Clinical trials of several proposed neuroprotective and neurotrophic
      applications have been done or are in progress. CONCLUSIONS: Erectile dysfunction
      is a well recognized and yet ineffectively averted complication of pelvic
      surgery. Neuromodulatory therapy offers a therapeutic approach for addressing the
      neuropathic changes of the penis that occurs in this context with the goal of
      maximally preserving erectile function postoperatively. While several specific
      neuromodulatory applications have gained interest for their potential benefit
      with pelvic surgery, determining their actual roles awaits the completion of
      controlled clinical trials.

PMID- 16890646
TI  - Activating mutations of Gsalpha in kidney cancer.
AB  - PURPOSE: Heterotrimeric G proteins are signal transduction proteins coupled to
      hormone receptors that activate intracellular second messenger systems, mainly
      cyclic adenosine monophosphate mediated protein kinase. Recent studies indicate
      that G proteins may have a major role in oncogenesis as well as in tumor
      invasiveness and cell proliferation. The involvement of G proteins was formerly
      thought to be limited to hormonal signal transduction. Activating Gsalpha
      mutations have been reported in tumors arising only from highly specialized
      endocrine tissue, such as pituitary adenomas, toxic thyroid adenomas and
      differentiated thyroid carcinomas, but never in other nonendocrine tumors. We
      hypothesized that a constitutive activation of this pathway, that is activated
      Gsalpha and inhibited Gialpha, could be implicated in kidney cancers. We searched
      for alterations on the Gsalpha gene GNAS and the Gialpha gene in renal cell
      carcinoma. MATERIALS AND METHODS: Using nested polymerase chain reaction, enzyme
      digestions, laser microdissection and direct sequencing we looked for activating
      mutations on GNAS codons 201 and 227, and inhibiting mutations on the Gialpha
      gene in 30 consecutive patients with clear cell renal cell carcinoma between
      January 2003 and January 2004. RESULTS: Somatic (tumor specific) activating
      mutations of Gsalpha were present in a significant proportion of human clear cell
      renal cell carcinomas. Activating mutations were identified in 5 of the 30
      patient DNA preparations (16.6%) with a substitution of arginine 201 by cysteine
      in 3 and histidine in 2. CONCLUSIONS: These findings suggest the implication of
      this pathway in human oncogenesis. It may provide a potential therapeutic
      approach to these frequent and aggressive tumors.

PMID- 16890647
TI  - Are small renal tumors harmless? Analysis of histopathological features according
      to tumors 4 cm or less in diameter.
AB  - PURPOSE: Small renal tumors detected incidentally are considered to have less
      aggressive potential. This assumption is mainly based on the low tendency to
      increase in size on serial imaging studies, but histopathological parameters of
      progression in larger patient series are scant. MATERIALS AND METHODS: We
      reviewed data of 287 tumor bearing kidneys in which solid tumors 4 cm or less in
      diameter were detected by cross-sectional imaging and subsequently removed
      surgically. Tumor size as documented by preoperative computerized tomography was
      correlated to histological diagnosis, and in cases of malignancy correlated to
      tumor type, pathological TNM stage and nuclear (Fuhrman) grade. With multifocal
      lesions the largest single tumor was considered the reference lesion but
      multifocality was also considered a separate parameter. RESULTS: At a mean tumor
      diameter of 2.94 +/- 0.87 cm 65 (22.6%) tumors were 2 cm or less, 103 (35.9%)
      were 2.1 to 3.0 cm and 119 (41.5%) were 3.1 to 4 cm in diameter. A total of 56
      (19.5%) tumors were benign with no correlation to tumor size (Pearson test p =
      0.660). Renal cell cancer was found in 227 (79.1%) patients with 159 (70.0%)
      clear cell, 47 (20.7%) papillary, 11 (4.8%) chromophobe and 10 others with no
      correlation to tumor diameter. Of the kidneys 31 (13.6%) had multifocal renal
      cell carcinoma, with a significant correlation to larger tumor diameter (linear
      regression p = 0.048) and papillary renal cell carcinoma subtype (linear
      regression p = 0.018). Two (4.2%), 4 (5%) and 25 (25.5%) cases of renal cell
      carcinoma 2 cm or less, 2.1 to 3 cm and 3.1 to 4 cm in diameter had Fuhrman grade
      G3/4, respectively (Pearson p = 0.0007). Advanced stage (pT3a or greater) was
      documented in 2 (4.2%), 12 (14.9%) and 35 (35.7%) cases for the same categories,
      respectively (p = 0.0023). Whereas distant metastases were diagnosed in only 4
      patients with renal cell carcinoma with tumors 3 cm or less, distant metastases
      were in 10 (8.4%) patients with tumors 3.1 to 4 cm (p = 0.045). CONCLUSIONS: The
      aggressive potential of small renal cell carcinoma increases dramatically beyond
      a tumor diameter of 3 cm. Given the difficulty in measuring tumor diameters
      reliably with sequential imaging studies, the threshold for selecting patients
      for a surveillance strategy should be set well under this parameter.

PMID- 16890648
TI  - Second primary malignancies associated with renal cell carcinoma histological
      subtypes.
AB  - PURPOSE: Renal cell carcinoma has been linked to numerous secondary malignancies.
      We evaluated the risk of secondary malignancies by renal cell carcinoma
      histological subtype in patients with clear cell, papillary and chromophobe renal
      cell carcinoma. MATERIALS AND METHODS: We studied 2,722 patients who underwent
      nephrectomy for sporadic renal cell carcinoma at our institution between 1970 and
      2000. All specimens were reviewed by a single urological pathologist for
      histological subtype. Associations of second primary malignancies by histological
      subtype were evaluated using the chi-square and Fisher exact tests. RESULTS: Of
      the patients studied 2,188 (80.4%) had clear cell, 378 (13.9%) had papillary and
      128 (4.7%) had chromophobe renal cell carcinoma. Patients with papillary renal
      cell carcinoma were significantly more likely to have colon cancer (p = 0.041),
      prostate cancer (p = 0.003), any second malignancy (p <0.001) and multiple
      malignancies (p <0.001) compared with patients with clear cell renal cell
      carcinoma. In addition, patients with chromophobe renal cell carcinoma were
      significantly more likely to have colon cancer than patients with clear cell
      renal cell carcinoma (p = 0.020). Although patients with papillary renal cell
      carcinoma were more likely to have bladder cancer, the incidence did not differ
      significantly compared with that in patients harboring clear cell and chromophobe
      renal cell carcinoma (p = 0.193). We did not find a significant difference in the
      incidence of breast cancer, lung cancer, rectal cancer or lymphoma among
      histological subtypes. CONCLUSIONS: Our data indicate that patients with
      papillary renal cell carcinoma are more likely to harbor secondary malignancies,
      including colon and prostate cancer, than patients with clear cell renal cell
      carcinoma. These results may have important implications for patient education
      and followup evaluation, and they should prompt mechanistic investigations.

PMID- 16890650
TI  - Fat poor renal angiomyolipoma: patient, computerized tomography and histological
      findings.
AB  - PURPOSE: We reviewed our experience with fat poor cases of angiomyolipoma.
      MATERIALS AND METHODS: The records of patients with angiomyolipoma, as determined
      by pathological study, from 1998 to 2004 were reviewed by recording patient
      demographics and outcomes. Fat poor cases were defined as the failure of imaging
      to demonstrate fat in a lesion. Computerized tomography and histological
      characteristics were assessed. RESULTS: Histologically confirmed angiomyolipoma
      was found in 15 patients. Multiple lesions were found in 3 of 15 cases (20%). Of
      these 15 patients who underwent surgery 11 (73%) had unsuspected angiomyolipoma
      due to absent fat on computerized tomography and they underwent intervention for
      presumed renal cell carcinoma. Mean age +/- SD in this group was 54 +/- 15 years
      and 8 of 11 patients (73%) were female, of whom 4 (50%) had uterine fibroids.
      These lesions were found incidentally in 7 of 11 cases (64%). Operative
      complications developed in 2 of 11 patients (18%). Average maximal diameter on
      pathological evaluation was 3.2 +/- 1.3 cm (range 1.5 to 6). Nonenhanced
      computerized tomography was available in 7 of 11 cases, of which 3 of 7 (42%)
      showed hyperdense lesions and 4 of 7 (57%) showed isodense lesions. The percent
      of fat identified per high power field was less than 25% in 12 of 13 fat poor
      angiomyolipoma lesions (92%) compared to 2 of 4 classic lesions (50%) known to be
      angiomyolipoma before surgery (p = 0.04). CONCLUSIONS: We suggest that a general
      definition of fat poor angiomyolipoma should be the failure of imaging to reveal
      fat within a lesion, thus, making it unsuspected at surgery. A pathological
      definition should be less than 25% fat per high power field, which to our
      knowledge is a formerly undefined quantity. Not all cases are hyperdense on
      nonenhanced computerized tomography. These lesions cannot be reliably identified
      by imaging and they should be managed like all enhancing renal masses.

PMID- 16890651
TI  - Tumor necrosis as prognostic indicator in transitional cell carcinoma of the
      upper urinary tract.
AB  - PURPOSE: The clinicopathological features predictive of outcome in patients with
      upper urinary tract transitional cell carcinoma are not clearly established. We
      analyzed the prognostic impact of tumor necrosis with respect to metastasis-free
      survival. MATERIALS AND METHODS: The presence of focal (10% or less of the tumor
      area) and extensive (greater than 10% of the tumor area) coagulative tumor
      necrosis was retrospectively reevaluated in 268 cases of consecutive upper
      urinary tract transitional cell carcinoma and correlated with outcome. RESULTS:
      Overall tumor necrosis was noted in 113 of 268 (42.2%) cases of transitional cell
      carcinoma with 63 (23.5%) showing focal and 50 (18.7%) showing extensive
      necrosis, respectively. Tumor necrosis was associated with high tumor stage (p
      <0.001) and high tumor grade (p <0.001). In addition, tumor necrosis was more
      common in pelvic tumors compared with ureteral tumors (p <0.001). Actuarial 5
      year metastasis-free survival rates for patients with transitional cell carcinoma
      with extensive, focal and lacking necrosis were 24%, 45% and 78%, respectively
      (log rank test p <0.001). Multivariate analysis proved pT stage greater than 1 (p
      <0.001, RR 6.04, 95% CI 2.82-12.93), high tumor grade (p <0.001, RR 3.37, 95% CI
      1.65-6.89) and extensive tumor necrosis as independent predictors of poor patient
      outcome (p = 0.02, RR 1.82, 95% CI 1.09-3.05). CONCLUSIONS: The presence of
      extensive tumor necrosis proved to be an additional histological variable with an
      independent influence on metastasis-free survival in patients with upper urinary
      tract transitional cell carcinoma. Its assessment is readily applicable in
      routine sections and should thus be commented upon separately in the pathology
      report.

PMID- 16890654
TI  - Percutaneous computerized tomography guided renal cryoablation using local
      anesthesia: pain assessment.
AB  - PURPOSE: The administration of intravenous sedation during prone computerized
      tomography guided, percutaneous procedures has the potential for complications.
      We assessed the pain associated with computerized tomography guided, percutaneous
      renal cryoablation using straight local anesthesia. MATERIALS AND METHODS:
      Patients were treated with cryoablation probes inserted into the renal tumor
      under computerized tomography guidance with local anesthesia. Patients were asked
      to rate the pain experienced during needle placement and cryoablation using a
      visual 10-degree pain score scale. Sedation was given when pain was greater than
      7 or when requested by the patient. Parameters assessed were cardiopulmonary
      complications, the need for intravenous supplementation, the pain score during
      the procedure and the postoperative score. RESULTS: A total of 25 patients (30
      tumors) underwent a total of 26 cryoablation sessions with only local anesthesia.
      Mean patient age +/- SD was 67 +/- 13 years (range 33 to 88). Average tumor and
      ice ball size was 2.1 +/- 0.7 (range 1.1 to 4.3) and 4.1 +/- 1.0 cm (range 2.6 to
      5.9), respectively. The mean dose of 1% lidocaine was 43.89 +/- 24.97 ml (range
      10 to 110). All procedures were completed in an average of 68.78 +/- 20.7 minutes
      (range 40 to 120). Vital signs were not significantly changed during the
      procedure. Successful completion of percutaneous computerized tomography guided
      cryoablation using local anesthesia was accomplished in 22 of the 26 sessions
      (84.62%) without sedation. Four patients required intravenous supplementation.
      CONCLUSIONS: Percutaneous computerized tomography guided cryoablation for renal
      tumors can be performed using local anesthesia with minimal discomfort in most
      patients.

PMID- 16890657
TI  - Racial disparity in bladder cancer: trends in tumor presentation at diagnosis.
AB  - PURPOSE: White Americans have a 2-fold higher incidence of bladder cancer than
      black Americans but the latter have a higher mortality rate. This survival
      disparity has been attributable largely to the late stage presentation of black
      patients but other factors likely exist. We examined trends in bladder cancer
      presentation and survival in white and black patients in a 27-year period to gain
      additional insight into these factors. MATERIALS AND METHODS: Using Surveillance,
      Epidemiology, and End Results Program data trends in tumor presentation,
      treatment and survival were defined in 93,093 patients, including 89,481 white
      and 3,612 black patients, with bladder cancer. Parameters were measured during 5
      and 7-year intervals from 1973 to 1999. Bivariate relationships between
      patient/disease characteristics, and the time and survival were explored. Cox
      proportional hazard models were used to examine the independent effect of
      parameters on disease specific survival. RESULTS: Median followup was 10 years.
      Black patients consistently presented with higher stage and grade tumors (each p
      <0.001). This was most pronounced in black women. A trend toward earlier stage
      presentation was observed in black and white patients with time (p = 0.05 and
      <0.001, respectively). Ten-year survival in black and white patients with similar
      tumor stage and grade was consistently worse in black patients, except those with
      metastasis. An adjusted multivariable model demonstrated a persistent survival
      disadvantage in black patients (HR 1.35, p <0.001). CONCLUSIONS: Racial
      disparities in bladder cancer stage, grade, treatment and adjusted survival
      continue to exist between white and black Americans despite improvements in stage
      presentation and survival of localized and regional disease. These data provide
      the rationale to study treatment decision making, access, delay and potential
      bias in the black community.

PMID- 16890655
TI  - Variability in the performance of nuclear matrix protein 22 for the detection of
      bladder cancer.
AB  - PURPOSE: We assessed variability in the diagnostic performance of NMP22 for
      detecting recurrence and progression in patients with Ta, T1, and/or CIS
      transitional cell carcinoma of the bladder in a large international cohort.
      MATERIALS AND METHODS: NMP22 voided urine levels were measured in 2,871 patients
      who underwent office cystoscopy for monitoring previous stage Ta, T1 and/or CIS
      transitional cell carcinoma at 12 participating institutions. RESULTS: Patient
      characteristics varied considerably among institutions. Overall 1,045 patients
      (36.4%) had recurrent transitional cell carcinoma (range across institutions
      13.6% to 54.3%). Median NMP22 was 5.5 U/ml (range across institutions 2.5 to
      18.8). Of the patients 33.5% had grade III tumors (range across institutions
      20.6% to 54.0%) and 22.4% had muscle invasive tumors (range across institutions
      3.2% to 38.2%). Area under the ROC curve for bladder TCC detection was 0.735 (95%
      CI 0.715 to 0.755, range across institutions 0.676 to 0.889). The manufacturer
      recommended cutoff of 10 U/ml detected 57% of cases with a 19% false-positive
      rate. AUC for grade III and stage T2 or greater disease was 0.806 (95% CI 0.780
      to 831) and 0.864 (95% CI 0.839 to 0.890), respectively. For each NMP22 cutoff
      NMP22 had higher sensitivity for detecting grade III and stage T2 or greater
      bladder transitional cell carcinoma than for detecting any cancer. No optimal
      cutoffs for detecting any or aggressive bladder transitional cell carcinoma could
      be derived based on NMP22 values. CONCLUSIONS: There is a substantial degree of
      heterogeneity in the diagnostic performance of NMP22 applied to populations from
      different institutions. There is no clearly defined NMP22 cutoff but there is a
      continuum of risk for recurrence and progression.

PMID- 16890660
TI  - The effect of ofloxacin on bacillus calmette-guerin induced toxicity in patients
      with superficial bladder cancer: results of a randomized, prospective, double
      blind, placebo controlled, multicenter study.
AB  - PURPOSE: We determined whether prophylaxis with ofloxacin could decrease the
      toxicity of bacillus Calmette-Guerin for transitional cell carcinoma of the
      bladder. We also investigated the impact of ofloxacin on bacillus Calmette-Guerin
      antitumor efficacy. MATERIALS AND METHODS: In this randomized, double-blind,
      multicenter study 115 patients with primary or recurrent superficial bladder
      cancer (Ta/T1, CIS, G1-G3) and no prior bacillus Calmette-Guerin treatment were
      randomized to induction treatment with intravesical bacillus Calmette-Guerin (6
      plus 3 instillations) plus 200 mg ofloxacin in group 1 or plus placebo in group
      2. Adverse events were assessed using a detailed grid of classification for
      bacillus Calmette-Guerin related adverse events. Mean patient age +/- SD was 65.6
      +/- 10.4 years in the 57 group 1 patients and 65.7 +/- 8.7 years in the 58 in
      group 2. Median followup was 369 and 374 days in groups 1 and 2, respectively.
      RESULTS: Ofloxacin significantly decreased by 18.5% the incidence of class II or
      higher moderate and severe adverse events between instillations 4 and 6. The
      percent of class III adverse events was significantly decreased by ofloxacin
      between instillations 1 and 9. Although ofloxacin decreased adverse events
      involving the lower urinary tract, it did not prevent class I adverse events.
      Compliance with full bacillus Calmette-Guerin treatment was also improved. Of
      patients in group 1, 80.7% received 9 instillations compared with 65.5% in group
      2 (p = 0.092). At 12 months recurrence and progression rates in group 1 and 2
      were 12.7% and 17.2%, and 5.5% and 1.7%, respectively. CONCLUSIONS: Prophylactic
      ofloxacin decreased the incidence of moderate to severe adverse events associated
      with bacillus Calmette-Guerin intravesical therapy, particularly class III
      events, which are primarily associated with patient dropout. Compliance with
      induction and maintenance therapy may be improved by adjuvant ofloxacin therapy.
      However, long-term comparative studies with other preventive strategies must be
      done to confirm these initial findings with compliance and recurrence-free
      survival as the primary end points.

PMID- 16890661
TI  - Contribution of 11C-choline positron emission tomography/computerized tomography
      to preoperative staging of advanced transitional cell carcinoma.
AB  - PURPOSE: Current imaging modalities for preoperative staging of advanced
      transitional cell carcinoma of the bladder or upper urinary tract are not
      sensitive for detection of metastases. This study examines the contribution of
      11C-choline positron emission tomography/computerized tomography to preoperative
      staging of transitional cell carcinoma. MATERIALS AND METHODS: We prospectively
      evaluated 18 patients with 19 advanced transitional cell carcinomas (17 bladder
      tumors and 2 upper tract transitional cell carcinomas). All patients had
      computerized tomography of the chest, abdomen and pelvis negative for metastases.
      11C-choline positron emission tomography/computerized tomography was performed on
      a Discovery ST(R) positron emission tomography/computerized tomography system.
      Finally 16 patients underwent radical surgery and positron emission
      tomography/computerized tomography images were compared to histopathological
      findings. Two patients were not operated on due to the findings on 11C-choline
      positron emission tomography/computerized tomography. RESULTS: 11C-choline uptake
      was found in all primary transitional cell carcinomas, with a maximum
      standardized uptake value of 7.3 +/- 3.2 (mean +/- SD). The series included 3
      patients with refractory bladder carcinoma in situ, which was visualized in all
      3, with a standardized uptake value of 6.9 +/- 5.6. In 6 patients uptake of 11C
      choline in lymph nodes as small as 5 mm was visualized (standardized uptake value
      3.8 +/- 1.4). Of these patients 4 underwent surgery and histopathology confirmed
      malignancy in 3 of 4. No additional patients with positive lymph nodes were found
      on histopathology. Metastases were visualized in bones with normal architecture
      on computerized tomography in 4 patients (standardized uptake value 5.2 +/- 1.1)
      and were confirmed by followup computerized tomography. CONCLUSIONS: In this
      small series 11C-choline positron emission tomography/computerized tomography was
      highly sensitive for primary and metastatic transitional cell carcinoma.
      Carcinoma in situ, lymph node metastases and early bony metastases were
      visualized. 11C-choline positron emission tomography/computerized tomography is a
      promising tool for preoperative staging of advanced transitional cell carcinoma.

PMID- 16890663
TI  - A multimodal perioperative plan for radical cystectomy and urinary intestinal
      diversion: effects, limits and complications of early artificial nutrition.
AB  - PURPOSE: We evaluated the effects of early parenteral and enteral postoperative
      nutritional support on the restoration of normal bowel function, on the protein
      depletion that follows cystectomy and on observed complications. MATERIALS AND
      METHODS: Immediate parenteral nutrition was initiated after surgery. It was
      progressively shifted to the enteral route through a needle catheter jejunostomy
      inserted at surgery. RESULTS: A total of 28 patients with a mean age of 74.2
      years (range 55 to 82) were enrolled into the study. Disease was pathologically
      confined to the bladder in 22 patients, locally advanced in 3 and extravesical in
      3. Urinary diversions included an ileocolonic pouch in 15 patients and an
      orthotopic ileal reservoir in 13. Of the 28 patients 15 (53.6%) completed the
      protocol, whereas 13 (46.4%) did not. Median time to peristalsis and spontaneous
      passage of flatus was postoperative day 2 (range 2 to 5) and median time to
      normal diet resumption was postoperative day 4 (range 3 to 8). No significant
      differences were observed between patients who completed the protocol and those
      who did not with regard to the restoration of normal bowel function, and total
      protein, serum albumin and lymphocyte count. Minor complications were observed in
      9 patients and major complications developed in 4. CONCLUSIONS: Early
      postoperative artificial nutrition did not affect the return of bowel function or
      postoperative protein depletion. Different strategies for more effective
      nutritional support will be explored in further studies.

PMID- 16890665
TI  - 11C-choline positron emission tomography/computerized tomography for tumor
      localization of primary prostate cancer in comparison with 12-core biopsy.
AB  - PURPOSE: (11)C-choline positron emission tomography is an innovative imaging
      technique for prostate cancer. We assessed the sensitivity of positron emission
      tomography used together with computerized tomography for intraprostatic
      localization of primary prostate cancer on a nodule-by-nodule basis, and compared
      its performance with 12-core transrectal biopsy. MATERIALS AND METHODS: In 43
      patients with known prostate cancer who had received positron emission
      tomography/computerized tomography before initial biopsy, we assessed sensitivity
      of positron emission tomography/computerized tomography for localization of
      nodules 5 mm or greater (those theoretically large enough for visualization)
      using radical prostatectomy histopathology as the reference standard. Comparison
      with transrectal ultrasound guided biopsy was based on sextant assessment of all
      cancer foci following sextant-by-sextant matching and reconstruction.
      Sensitivity/specificity of positron emission tomography/computerized tomography
      and magnetic resonance imaging for prediction of extraprostatic extension was
      also assessed. RESULTS: Positron emission tomography/computerized tomography
      showed 83% sensitivity for localization of nodules 5 mm or greater. At logistic
      regression analysis only nodule size appeared to influence sensitivity. At
      sextant assessment positron emission tomography/computerized tomography had
      slightly better sensitivity than transrectal ultrasound guided biopsy (66% vs
      61%, p = 0.434) but was less specific (84% vs 97%, p = 0.008). For assessment of
      extraprostatic extension, sensitivity of PET/CT was low in comparison with
      magnetic resonance imaging (22% vs 63%, p <0.001). CONCLUSIONS: Positron emission
      tomography/computerized tomography has good sensitivity for intraprostatic
      localization of primary prostate cancer nodules 5 mm or greater. Positron
      emission tomography/computerized tomography and transrectal ultrasound guided
      biopsy show similar sensitivity for localization of any cancer focus. Positron
      emission tomography/computerized tomography does not seem to have any role in
      extraprostatic extension detection. Studies of diagnostic accuracy (as opposed to
      tumor localization) are needed in patients with suspected prostate cancer to see
      whether positron emission tomography/computerized tomography could have a role in
      not selected patients.

PMID- 16890668
TI  - Prostate saturation biopsy in the reevaluation of microfocal prostate cancer.
AB  - PURPOSE: We evaluated the ability of an extended, 32-core repeat transrectal
      ultrasound prostate biopsy protocol to improve the characterization of low
      volume, well differentiated disease in men with a diagnosis of potentially
      insignificant microfocal prostate cancer, as defined by 1 single focus positive
      core of 10 with less than 5 mm of Gleason score 6 or less tumor on primary
      biopsy. MATERIALS AND METHODS: A total of 35 consecutive patients, who were 62 to
      75 years old, had a median serum prostate specific antigen of 8 ng/ml (range 0.5
      to 14) and a diagnosis of minimal prostate cancer, and were willing to consider
      observation with delayed treatment at progression, were offered repeat saturation
      prostate biopsy with a median of 32 cores (range 18 to 36) under local
      anesthesia. This biopsy was to determine whether more extensive prostate sampling
      would confirm or disprove the initial diagnosis of microfocal, well
      differentiated prostate cancer. RESULTS: The procedure was aborted in 1 patient
      because of massive rectal hemorrhage. Another patient had acute prostatitis with
      gram-negative sepsis. Of 34 evaluable biopsy sets 11 (32%) were negative for
      cancer, suggesting that tumor detected at the primary biopsy was probably of low
      volume and amenable to observation with delayed treatment. Of the biopsies 23
      (68%) were positive, 17 were at multiple sites and 7 were upgraded to Gleason
      score 7 or greater. These patients were then considered to have significant
      tumors and were offered active treatment. CONCLUSIONS: This study is to our
      knowledge the first to describe the clinical use of prostate saturation biopsies
      for re-evaluating potentially insignificant prostate cancer. Of patients with
      minimal disease on standard 10-core biopsy, results show that this technique may
      be helpful for distinguishing the 30% who probably have minimal disease based on
      negative repeat saturation biopsy from the 70% who almost certainly have a
      significant tumor, as characterized by multiple positive cores, with or without
      an increased Gleason score. The latter patients should be offered active therapy.

PMID- 16890670
TI  - Toremifene for the prevention of prostate cancer in men with high grade prostatic
      intraepithelial neoplasia: results of a double-blind, placebo controlled, phase
      IIB clinical trial.
AB  - PURPOSE: A randomized, double-blind, dose finding, placebo controlled, parallel
      group clinical study was done to determine the incidence of prostate cancer in
      men with high grade prostatic intraepithelial neoplasia treated with toremifene.
      MATERIALS AND METHODS: A total of 514 patients with high grade prostatic
      intraepithelial neoplasia and no evidence of prostate cancer on screening biopsy
      were randomized to 20, 40 or 60 mg toremifene, or placebo daily for 12 months.
      Patients underwent re-biopsy at 6 and 12 months. RESULTS: The number of evaluable
      patients, that is those with 1 on study biopsy who were compliant, was 447. The
      cumulative risk of prostate cancer was decreased in patients on 20 mg toremifene
      compared with placebo (24.4% vs 31.2%, p <0.05). The annualized rate of
      prevention was 6.8 cancers per 100 men treated. In patients with no biopsy
      evidence of cancer at baseline and 6 months, the 12-month incidence of prostate
      cancer was decreased by 48.2% with 20 mg toremifene compared with placebo (9.1%
      vs 17.4%, p <0.05). The 20 mg dose was most effective but cumulative and 12-month
      incidences of prostate cancer were lower for each toremifene dose vs placebo with
      a cumulative risk of 29.2% and 28.1%, and a 12-month incidence of 14.3% and 13.0%
      for 40 and 60 mg, respectively. Gleason scores were similar across treatments.
      The overall incidence of drug related and serious adverse events did not differ
      between any of the toremifene groups and the placebo group. CONCLUSIONS:
      Toremifene decreased the incidence of prostate cancer by 1 year and had a
      tolerability profile comparable to that of placebo in a high risk population.

PMID- 16890673
TI  - Zoledronic acid initiated during the first year of androgen deprivation therapy
      increases bone mineral density in patients with prostate cancer.
AB  - PURPOSE: Androgen deprivation therapy in patients with prostate cancer is
      associated with bone loss and an increased risk of fractures. Zoledronic acid
      protects against bone mineral density loss when initiated concurrently with
      androgen deprivation therapy. We evaluated the effect of zoledronic acid
      initiated subsequent to androgen deprivation therapy on bone mineral density and
      biochemical markers of bone turnover. MATERIALS AND METHODS: Patients with
      prostate cancer without bone metastases who had received androgen deprivation
      therapy for 12 months or less were randomized to 4 mg zoledronic acid or placebo
      intravenously every 3 months for 1 year. Patients were stratified according to
      androgen deprivation therapy duration (less than 6 vs 6 to 12 months). The
      primary end point was the change in femoral neck and lumbar spine bone mineral
      density in the 2 groups. The secondary end point was the change in serum bone
      specific alkaline phosphatase and urine N-telopeptide levels. Total hip bone
      mineral density was also measured. RESULTS: The 120 patients with prostate cancer
      received zoledronic acid (61) or placebo (59). Compared with placebo, zoledronic
      acid increased femoral neck, total hip and lumbar spine bone mineral density
      yearly by 3.6% (p = 0.0004), 3.8% (p <0.0001) and 6.7% (p <0.0001), respectively.
      The effects of zoledronic acid on bone mineral density at these 3 sites were not
      differentiated according to androgen deprivation therapy duration. Additionally,
      mean bone specific alkaline phosphatase and N-telopeptide levels were decreased
      in the zoledronic acid group (each p <0.0001) and were increased in the placebo
      group (p <0.0001 and p = 0.004, respectively). CONCLUSIONS: Zoledronic acid
      increased bone mineral density and suppressed bone turnover markers in patients
      with prostate cancer without bone metastases when initiated during year 1 of
      androgen deprivation therapy.

PMID- 16890675
TI  - Prostate cancers scored as Gleason 6 on prostate biopsy are frequently Gleason 7
      tumors at radical prostatectomy: implication on outcome.
AB  - PURPOSE: Differentiation between Gleason score 6 and 7 in prostate biopsy is
      important for treatment decision making. Nevertheless, under grading errors
      compared with the actual pathological grade at radical prostatectomy are common.
      We compared the characteristics and outcomes of tumors that were scored 6 on
      prostate biopsy but were 7 on subsequent radical prostatectomy pathological
      evaluation to those in tumors with a consistent rating of Gleason score 6 or 7 at
      biopsy and surgery. MATERIALS AND METHODS: We performed a retrospective database
      analysis from our referral center (1989 to 2004). We compared pre-prostatectomy
      characteristics, radical prostatectomy pathological features and the post-radical
      prostatectomy prostate specific antigen failure rate, defined as any 2
      consecutive detectable prostate specific antigen measurements, in 3 subgroups of
      patients, including 156 with matched Gleason score 6 in the prostate biopsy and
      radical prostatectomy, 205 with upgraded Gleason score 6/7, that is prostate
      biopsy Gleason score 6 and radical prostatectomy Gleason score 7, and 412 with
      matched Gleason score 7 in the prostate biopsy and radical prostatectomy.
      RESULTS: Radical prostatectomy Gleason score matched the prostate biopsy score in
      38.2% of biopsy Gleason score 6 and 81.4% of biopsy Gleason score 7 cases. Higher
      prostate specific antigen was associated and an increased percent of cancer in
      the prostate biopsy was predictive of discordance between the prostate biopsy and
      radical prostatectomy Gleason scores (p <0.001). Margin (p = 0.0075) or seminal
      vesicle involvement (p = 0.0002), cancer volume (p <0.001) and the prostate
      specific antigen failures rate (p = 0.014) were significantly higher in under
      graded Gleason score 7 cancer compared to those in matched Gleason score 6 cases.
      However, they were comparable to those with a matched Gleason score 7 tumor grade
      (p = 0.66). CONCLUSIONS: Almost half of tumors graded Gleason score 6 at biopsy
      are Gleason score 7 at surgery. Upgraded Gleason score 6 to 7 tumors have
      outcomes similar to those of genuine Gleason score 7 cancer. For prostate biopsy
      Gleason score 6 tumors clinicians should consider the overall likelihood of tumor
      upgrading as well as specific patient characteristics, such as prostate specific
      antigen and the percent of tumor in the prostate biopsy, when contemplating
      treatments that are optimized for low grade tumors, including watchful waiting or
      brachytherapy.

PMID- 16890677
TI  - Salvage radiotherapy for isolated prostate specific antigen increase after
      radical prostatectomy: evaluation of prognostic factors and creation of a
      prognostic scoring system.
AB  - PURPOSE: This study was performed to evaluate the results and prognostic factors
      associated with radiotherapy for a detectable serum prostate specific antigen
      level after radical prostatectomy. MATERIALS AND METHODS: From July 1987 through
      July 2003, 368 patients received radiotherapy for a detectable prostate specific
      antigen level (biochemical relapse) as the sole evidence of recurrence after
      radical prostatectomy for node negative prostate cancer. Estimated survival and
      relapse-free probabilities were obtained via Kaplan-Meier estimation.
      Associations of patient factors with survival and biochemical relapse were
      investigated using Cox proportional hazards models. RESULTS: With a median
      followup of 5 years the 5 and 8-year freedom from biochemical relapse were an
      estimated 46% (95% CI 41%-53%) and 35% (95% CI 29%-43%) while survival was 92%
      (95% CI 89%-95%) and 80% (95% CI 74%-87%), respectively. Patient and treatment
      variables showing evidence of association with biochemical relapse on
      multivariate analysis included pathological stage T3a or less vs T3b (seminal
      vesicle involvement, p = 0.029), pathological Gleason score 7 or less vs 8 or
      greater (p <0.001) and pre-radiotherapy prostate specific antigen (p <0.001).
      Four biochemical failure risk groups were created by assigning seminal vesicle
      involvement, Gleason score and pre-radiotherapy prostate specific antigen each a
      score of 0 to 2. These individual scores were summed. The freedom from
      biochemical failure at 5 years for each risk group was 0 to 1-69%, 2-53%, 3-26%
      and 4 to 5-6%. CONCLUSIONS: The presence of seminal vesicle involvement and high
      Gleason score in the radical prostatectomy specimen are inherent predictors of
      adverse outcome. Early referral for salvage radiotherapy can decrease subsequent
      biochemical relapse.

PMID- 16890678
TI  - Poorly differentiated prostate cancer treated with radical prostatectomy: long
      term outcome and incidence of pathological downgrading.
AB  - PURPOSE: Patients with high grade (Gleason score 8 to 10) prostate cancer on
      biopsy are at high risk for cancer recurrence after local treatment, such as
      radiation therapy and radical prostatectomy. We examined long-term outcomes in
      patients with high grade prostate cancer on biopsy who were treated with radical
      prostatectomy alone. We also investigated the impact on outcomes of changes in
      the radical prostatectomy Gleason score. MATERIALS AND METHODS: Of 5,662 patients
      who underwent radical prostatectomy during 20 years 238 had a biopsy Gleason
      score of 8 to 10. We analyzed the rate of biochemical recurrence in this subgroup
      according to the Gleason grade of cancer in the radical prostatectomy specimen.
      RESULTS: Ten-year biochemical recurrence-free probability in the cohort was 39%.
      However, 45% of patients (95% CI 38 to 51%) with Gleason score 8 to 10 cancer on
      biopsy had a Gleason score of 7 or less in the radical prostatectomy specimen.
      These patients had a 10-year biochemical recurrence-free probability of 56%
      compared to 27% in those with a final Gleason score that remained 8 to 10 (p =
      0.0004). On multivariate analysis neither prostate specific antigen nor biopsy
      features, including total number of cores, number of cores with cancer and
      percent of cancer in the cores, was a significant predictor of downgrading.
      However, clinical stage and biopsy Gleason score were significant with 58% of
      cT1c and 51% of biopsy Gleason score 8 cancers downgraded. Almost 65% of cT1c
      Gleason score 8 cancers were downgraded compared to 11% of cT3 Gleason score 9
      cancers. CONCLUSIONS: Patients diagnosed with poorly differentiated prostate
      cancer (Gleason score 8 to 10) on biopsy do not uniformly have a poor prognosis.
      Of the patients 39% remain free of cancer recurrence 10 years after radical
      prostatectomy. Of these cancers 45% have a lower Gleason score in the radical
      prostatectomy specimen and a correspondingly more favorable long-term outcome.
      Predictors of downgrading are lower clinical stage (cT1c) and Gleason score 8 in
      the biopsy specimen.

PMID- 16890679
TI  - Uronate peaks and urinary hyaluronic acid levels correlate with interstitial
      cystitis severity.
AB  - PURPOSE: Levels of uronate, a basic component of urothelial glycosaminoglycans,
      are increased in urine specimens of patients with interstitial cystitis with
      severe symptoms. In this study we examined the urinary glycosaminoglycan profile
      and correlated the profile and urinary hyaluronic acid (a glycosaminoglycan)
      levels with symptom severity. MATERIALS AND METHODS: Urine specimens and
      completed O'Leary-Sant interstitial cystitis symptom and problem indexes
      questionnaires were obtained from 29 patients with interstitial cystitis, 14
      normal individuals, and 14 patients with other benign pelvic and bladder
      conditions. Patients with interstitial cystitis were divided into group 1-1 or
      both indexes less than 50% maximum score, and group 2-both indexes 50% of maximum
      score or greater. All patients met the National Institutes of Diabetes and
      Digestive and Kidney Diseases criteria except regarding glomerulation. In a
      followup study 30 urine specimens were collected from 8 patients with
      interstitial cystitis and from 4 normal individuals during 12 months. The urinary
      glycosaminoglycan profile was determined by gel filtration chromatography.
      Glycosaminoglycan peaks were analyzed by polyacrylamide gel electrophoresis.
      Urinary hyaluronic acid levels were determined by the hyaluronic acid test.
      RESULTS: Group 2 urine specimens contained 3 uronate peaks, whereas urine
      specimens from normal individuals and patients in group 1 contained 1 or 2 peaks.
      Peak 1 consisted of macromolecular glycosaminoglycans whereas peaks 2 and 3
      contained oligosaccharides. Urinary hyaluronic acid levels were 3 to 4-fold
      increased in group 2. Glycosaminoglycan profile and hyaluronic acid levels
      detected interstitial cystitis severity with 83% sensitivity, and 89.7% and 74.4%
      specificity, respectively. Interstitial cystitis urothelial cells/tissues also
      over expressed hyaluronic acid synthase 1 (which synthesizes hyaluronic acid)
      compared to normal urothelial cells/tissues. In the followup study urinary
      uronate levels, glycosaminoglycan profile and hyaluronic acid levels detected
      patients with severe symptoms with 73% sensitivity and 87% to 94% specificity. In
      both studies uronate, glycosaminoglycan profile and hyaluronic acid levels
      significantly correlated with interstitial cystitis severity (p <0.001).
      CONCLUSIONS: Urinary glycosaminoglycan profile, uronate content and hyaluronic
      acid levels are potentially useful markers for monitoring interstitial cystitis
      severity, and are likely to be involved in interstitial cystitis pathophysiology.

PMID- 16890680
TI  - Biofilm formation on clinically noninfected penile prostheses.
AB  - PURPOSE: Biofilms are matrix enclosed bacterial populations that adhere to each
      other and/or to surfaces of implanted medical devices. Biofilm formation has
      consistently been demonstrated in association with infected penile prosthetic
      material. Clinically noninfected patients undergoing revision for mechanical
      malfunction have a surprisingly high rate of positive intraoperative cultures.
      After revision replacement prostheses have a higher rate of postoperative
      infection than first time implants. We characterized biofilm formation on penile
      prostheses in clinically noninfected patients undergoing revision surgery.
      MATERIALS AND METHODS: Ten patients undergoing revision or removal of inflatable
      penile prosthetic devices due to mechanical malfunction were included. Specimens
      from the corporeal cylinders, scrotal pump and reservoir were analyzed. Bacterial
      biofilm coverage was detected and characterized using confocal scanning laser
      microscopy. RESULTS: Bacterial biofilm formation associated with multiple
      microorganisms was demonstrated on 8 of 10 prostheses. Biofilms consisted of gram
      positive rods, cocci and fungal elements. CONCLUSIONS: The degree of biofilm
      formation on these prosthetic devices suggests that most patients have bacterial
      coverage on the implant. Host mechanisms to control infection may lead to a
      homeostatic balance that enables biofilms to exist on the surface of the
      prosthesis without generating clinical infection. A critical threshold of biofilm
      extent may exist beyond which clinical infection may occur. These results justify
      further evaluation of biofilms and penile prosthesis infections. Furthermore, the
      findings help to explain why strategies such as mini salvage procedures to
      eliminate subclinical biofilms may decrease the postoperative infection risk in
      patients undergoing repair or replacement of penile prostheses.

PMID- 16890681
TI  - The influence of chronic inflammation in prostatic carcinogenesis: a 5-year
      followup study.
AB  - PURPOSE: We investigated an association between chronic prostatic inflammation
      and prostate carcinogenesis. MATERIALS AND METHODS: Initial prostate needle
      biopsies from 177 patients with clinical parameters suspicious for malignancy
      were examined. We evaluated them for the presence and extent of chronic
      inflammation and other pathological findings. Findings in followup biopsies
      during the next 5 years were reviewed and correlated with the initial results.
      RESULTS: Two patients subset were identified, including 144 patients with and 33
      without chronic inflammation in the initial biopsies. Additional pathological
      findings in some cases in each group included simple atrophy, high grade
      prostatic intraepithelial neoplasia, adenocarcinoma and atypical small acinar
      proliferation. Post-atrophic hyperplasia and proliferative inflammatory atrophy
      were noted only in patients with chronic inflammation. A significant association
      between serum prostate specific antigen and the degree of inflammation was
      observed in needle biopsies. In repeat biopsies within 5 years in patients with
      chronic inflammation 29 new cancers were diagnosed, representing a new cancer
      incidence of 20%. Of these cancers 6 occurred in patients in whom initial
      biopsies showed only chronic inflammation, 15 occurred in patients with initial
      post-atrophic hyperplasia/proliferative inflammatory atrophy lesions, 7 occurred
      in patients with initial high grade prostatic intraepithelial neoplasia and
      chronic inflammation, and 1 occurred in a patient with initial atypical small
      acinar proliferation and chronic inflammation. High grade prostatic
      intraepithelial neoplasia was newly discovered in 9 patients in the initial
      chronic inflammation group, of whom 7 had post-atrophic hyperplasia/proliferative
      inflammatory atrophy and 2 had simple atrophy and chronic inflammation in the
      initial biopsies. In contrast, in 33 patients initially showing no inflammation
      adenocarcinoma was subsequently found in 2 (6%). One of these patients had high
      grade prostatic intraepithelial neoplasia and the other had atypical small acinar
      proliferation on initial biopsies. CONCLUSIONS: Chronic inflammation may be a
      significant risk factor for prostatic adenocarcinoma.

PMID- 16890682
TI  - Can Phyllanthus niruri affect the efficacy of extracorporeal shock wave
      lithotripsy for renal stones? A randomized, prospective, long-term study.
AB  - PURPOSE: Phyllanthus niruri is a plant used in Brazilian folk medicine for the
      treatment of urolithiasis. We assessed the efficacy of P. niruri after
      extracorporeal shock wave lithotripsy for renal stones. MATERIALS AND METHODS: We
      prospectively evaluated 150 patients with renal stones that were as large as 25
      mm and composed of calcium oxalate. All patients received 1 to 3 extracorporeal
      shock wave lithotripsy sessions by Dornier Lithotriptor S. After treatment 78 of
      150 patients (52%) underwent therapy with Uriston, a P. niruri extract (2 gm
      daily) for at least 3 months (group 1). Otherwise 72 of 150 patients (48%) were
      used as a control group (group 2). No significant difference in stone size
      between the 2 groups was found. Stone clearance was assessed after 30, 60, 90 and
      180 days by abdominal x-ray and ultrasound scan. RESULTS: Stone-free rate (stone
      free defined as the absence of any stone or residual fragments less than 3 mm)
      was 93.5% in group 1 and 83.3% in group 2 (p = 0.48) at the end point of the
      followup (180 days). For lower caliceal stones (56 patients) the stone-free rate
      was 93.7% in the treatment group and 70.8% in the control group (p = 0.01). Re
      treatment need for group 1 was 39.7% and for group 2 it was 43.3% (p = 0.2). No
      side effects were recorded with extracorporeal shock wave lithotripsy or P.
      niruri therapy. CONCLUSIONS: Regular self-administration of P. niruri after
      extracorporeal shock wave lithotripsy for renal stones results in an increased
      stone-free rate that appears statistically significant for lower caliceal
      location. Its efficacy and the absolute lack of side effects make this therapy
      suitable to improve overall outcomes after extracorporeal shock wave lithotripsy
      for lower pole stones.

PMID- 16890683
TI  - Porcine small intestinal submucosa is not an ideal graft material for Peyronie's
      disease surgery.
AB  - PURPOSE: The incidence of Peyronie's disease is up to 7% in some series. While
      there are numerous nonsurgical methods of treatment, they do not have a high rate
      of success. Nesbit plication was once the accepted surgery for Peyronie's
      disease. Tunical lengthening procedures became popular because they avoided
      penile shortening caused by the Nesbit procedure. More urologists now perform
      plaque incision or excision, followed by grafting with different materials. Small
      intestinal submucosa offered promise as an ideal graft material. It is available
      off the shelf as 1 or 4-ply graft material. In several studies it appeared to
      function as a collagen based scaffold with graft incorporation in host tissue.
      MATERIALS AND METHODS: A single reconstructive urologist performed plaque
      incision and small intestinal submucosa grafting in 4 cases of Peyronie's disease
      using the same surgical technique. RESULTS: Although early results were positive,
      we have achieved less than satisfactory results with this material. The penis was
      straight in the immediate postoperative period but there was recurrent curvature
      in 3 of the 4 patients, of whom 2 had recurrence within 4 months of the
      procedure. CONCLUSIONS: We observed disappointing results with small intestinal
      submucosa for Peyronie's disease surgery with a high percent of recurrent
      curvature. Further studies are needed to determine if 1 or 4-ply small intestinal
      submucosa is an ideal graft material for the tunica albuginea.

PMID- 16890685
TI  - Nocturia and circadian blood pressure profile in healthy elderly male volunteers.
AB  - PURPOSE: Nocturia is attributed to nocturnal polyuria and/or decreased functional
      bladder capacity. In this study we elucidated the mechanisms behind circadian
      fluid regulation and the occurrence of nocturia in healthy elderly males,
      specifically to determine the role of urine output and regulating hormones, blood
      pressure, and average voided volumes. MATERIALS AND METHODS: A total of 18 males
      55 to 73 years old (mean age 61.1) were included in the study. Voiding habits
      were assessed by completion of a 7-day frequency volume chart recording all fluid
      intake and voiding. The subjects subsequently underwent inpatient circadian
      studies measuring the diurnal rhythm of blood pressure, vasopressin, atrial
      natriuretic peptide, angiotensin II, aldosterone and urine volume. RESULTS: Of
      the nightly home recordings 25% showed nocturia, characterized by a higher 24
      hour and nighttime urine volume. During the inpatient studies 12 of the 18
      participants experienced a nocturnal void. Nocturia nights were characterized by
      significantly decreased day-to-night ratios in urine output and a higher
      nighttime mean arterial blood pressure. A circadian variation in plasma arginine
      vasopressin was seen only in the group without nocturia. The other hormones
      revealed a circadian rhythm similar in the 2 groups. CONCLUSIONS: In healthy
      males with occasional nocturia, the occurrence of nocturia seems to be associated
      with a blunting of the circadian rhythm of diuresis and increased arterial blood
      pressures during the night. These findings may implicate a role for a
      baroregulatory related mechanism in nocturia.

PMID- 16890687
TI  - Voiding dysfunction following removal of eroded synthetic mid urethral slings.
AB  - PURPOSE: Voiding dysfunction following genitourinary erosion of synthetic mid
      urethral slings is not clearly reported. We investigated the incidence of voiding
      dysfunction in patients following sling excision due to vaginal, urethral or
      intravesical mesh erosion. MATERIALS AND METHODS: Retrospective review identified
      19 patients with genitourinary erosion of polypropylene mesh slings.
      Comprehensive urological evaluation was performed in all patients, and
      perioperative and postoperative data were analyzed. Voiding dysfunction was
      defined as refractory storage symptoms, emptying symptoms and pelvic pain. All
      subsequent medical and surgical interventions were recorded. RESULTS: In 19
      patients a total of 11 vaginal, 7 intravesical and 5 urethral erosions occurred.
      Mean patient age was 52 years (range 32 to 69) and average followup was 8.4
      months (range 3 to 34). Average time from symptom onset to sling removal was 10.1
      months (range 1.5 to 38). Of the 19 patients 14 (74%) presented with multiple
      symptoms. Symptoms varied, including refractory pain, recurrent infections and
      bladder storage/emptying dysfunction. Urodynamic studies were abnormal
      preoperatively and postoperatively in 9 of 13 (69%) and 4 of 6 patients (67%),
      respectively. Following surgery lower urinary tract symptoms resolved completely
      in only 4 of the 19 patients (21%). Stress incontinence recurred in 8 of the 19
      patients (42%). Five patients underwent simultaneous pubovaginal sling, of whom
      none had recurrent stress urinary incontinence. Only 9 patients (47%) considered
      themselves dry with no pads following surgery. Four patients required further
      surgery for refractory voiding symptoms. CONCLUSIONS: Voiding dysfunction is not
      an uncommon finding after sling excision in the setting of genitourinary erosion.
      It may cause additional patient morbidity.

PMID- 16890688
TI  - Dutasteride improves objective and subjective disease measures in men with benign
      prostatic hyperplasia and modest or severe prostate enlargement.
AB  - PURPOSE: We determined whether the effect of dutasteride for benign prostatic
      hyperplasia is influenced by baseline prostate volume using data from 3 phase III
      clinical trials. MATERIALS AND METHODS: Patients randomized to dutasteride or
      placebo in the double-blind portion of the phase III studies were eligible to
      receive 0.5 mg dutasteride daily in a 2-year open label extension in
      dutasteride/dutasteride and placebo/dutasteride groups. Patients were
      prospectively stratified according to baseline prostate volume 30 to less than 40
      and 40 cc or greater. RESULTS: In patients treated with dutasteride throughout
      the study (dutasteride/dutasteride group) the mean reduction in prostate volume
      from baseline to month 48 was 30.3% in those with a baseline prostate volume of
      30 to less than 40 cc and 26.2% in those with a prostate volume of 40 cc or
      greater. Mean improvements in peak urinary flow from baseline to month 48 were
      2.7 ml per second regardless of baseline prostate volume. Improvements in the
      American Urological Association symptom index score were 6.3 in men with a
      prostate volume of 30 to less than 40 cc and 6.5 in those with a prostate volume
      of 40 cc or greater. No significant relationships between treatment effect and
      baseline prostate volume were observed for these parameters. In
      dutasteride/dutasteride treated patients the risk of acute urinary retention was
      decreased by 60% in those with a prostate volume of 30 to less than 40 cc and 55%
      in those with a prostate volume of 40 cc or greater vs values in
      placebo/dutasteride treated patients (p = 0.036 and <0.001, respectively). The
      corresponding values for benign prostatic hyperplasia related surgery were 27%
      and 48% (p = 0.35 and <0.001, respectively). CONCLUSIONS: This analysis
      demonstrates that dutasteride significantly improves objective (prostate volume
      and peak urinary flow) and subjective (symptom scores) measures even in patients
      with only a slightly enlarged prostate (30 to less than 40 cc). The risks of
      acute urinary retention and benign prostatic hyperplasia related surgery were
      decreased regardless of baseline prostate volume.

PMID- 16890690
TI  - Response to daily 10 mg alfuzosin predicts acute urinary retention and benign
      prostatic hyperplasia related surgery in men with lower urinary tract symptoms.
AB  - PURPOSE: We analyzed the influence of treatment response on the risk of acute
      urinary retention and benign prostatic hyperplasia related surgery in 5,792 men
      complaining of lower urinary tract symptoms who were treated for 6 months with
      the selective alpha1-blocker alfuzosin at 10 mg once daily. MATERIALS AND
      METHODS: The influence of dynamic variables (International Prostate Symptom Score
      change and bother during treatment) and baseline variables (patient age, prior
      acute urinary retention managed conservatively, prostate specific antigen,
      International Prostate Symptom Score and bother severity) on the risk of acute
      urinary retention and benign prostatic hyperplasia related surgery was estimated
      using the Kaplan-Meier method and log rank test. The associated HR and 95% CI
      were calculated using Cox proportional hazard models. RESULTS: During alfuzosin
      treatment International Prostate Symptom Score improved by 3 or greater and
      greater than 6 points in 74.8% and 50.3% of men, respectively. In this unselected
      population, including 3.8% with prior unoperated acute urinary retention, the
      rate of acute urinary retention and benign prostatic hyperplasia related surgery
      events during treatment was low (0.5% and 1.1%, respectively). Men with stable or
      worsening International Prostate Symptom Score were at increased risk for acute
      urinary retention or surgery (HR 3.75, 95% CI 1.58 to 8.89, p = 0.003 and HR
      4.71, 95% CI 2.69 to 8.24, p <0.001, respectively). Prior acute urinary retention
      was a strong predictor of acute urinary retention relapse and surgery (HR 10.35,
      95% CI 4.29 to 26.08, p <0.001 and HR 3.57, 95% CI 1.59 to 7.98, p = 0.002,
      respectively). Bother score greater than 3 during treatment was the strongest
      predictor of surgery (HR 7.61, 95% CI 4.16 to 13.93, p <0.001). Prostate specific
      antigen had much less predictive value. CONCLUSIONS: This 6-month real life
      practice study shows that alfuzosin is associated with a low incidence of acute
      urinary retention and benign prostatic hyperplasia related surgery. It also
      suggests that responder status is the most important predictor of acute urinary
      retention and benign prostatic hyperplasia related surgery. Thus, first line
      treatment with alfuzosin may help select patients at risk for benign prostatic
      hyperplasia progression to optimize treatment.

PMID- 16890691
TI  - Incidence of ureteral strictures after laparoscopic donor nephrectomy.
AB  - PURPOSE: Previous reports of laparoscopic donor nephrectomy have suggested that
      preservation of the gonadal vein with the specimen is important for preventing
      ureteral strictures. To test this hypothesis we examined our series of patients
      for the incidence of ureteral strictures when the gonadal vein was not preserved
      with the specimen during laparoscopic donor nephrectomy. MATERIALS AND METHODS:
      We reviewed the records of 300 consecutive patients at our institution who
      underwent laparoscopic donor nephrectomy between 2000 and 2005. Mean donor age
      was 36.7 years (range 18 to 68) in the 167 female and 133 male donors. Mean
      recipient age was 38.4 years. Average followup was 2 years. During ureteral
      dissection the gonadal vein was transected just distal to the renal vein and left
      in situ. The ureter was dissected and transected at the level of the common iliac
      vessels. Indwelling ureteral stents were used for all recipient ureteral
      reimplantations and left in place for 1 month. In the postoperative period
      transplant recipients were followed biweekly for serum creatinine function during
      month 1 and monthly thereafter. All patients with increased creatinine (greater
      than 1.3 mg/dl) or an increasing trend were evaluated with transplant renal
      ultrasound. Clinically significant ureteral stricture was defined as persistent
      hydronephrosis resulting in impaired renal function and the need for percutaneous
      nephrostomy tube placement or ureteroscopic management. RESULTS: After
      laparoscopic living donor transplantation without gonadal vein preservation we
      found no incidence of clinically significant ureteral stricture. CONCLUSIONS:
      Gonadal vein preservation with the specimen during laparoscopic donor nephrectomy
      is not necessary. Preservation of the periureteral blood supply is sufficient to
      prevent ureteral strictures.

PMID- 16890692
TI  - Long-term outcome of cadaveric renal transplant after treatment of symptomatic
      lymphocele.
AB  - PURPOSE: Between January 1993 and December 2002 a total of 1,289 renal
      transplants were performed at our institution. Symptomatic post-transplant
      lymphocele presenting as increased creatinine and hydronephrosis of the allograft
      was recorded at 0.02%. Records of the 27 patients in whom symptomatic lymphocele
      developed and of those who underwent contralateral kidney transplant (control
      group) were compared to determine the long-term effects of lymphocele formation
      on allograft function. MATERIALS AND METHODS: A total of 37 procedures for the
      treatment of lymphocele were performed in 24 patients. Open marsupialization (12)
      and laparoscopic marsupialization (3) procedures were performed as primary
      treatments. Two patients underwent repeat open marsupialization. Aspiration and
      percutaneous catheter drainage were performed as a primary procedure in 7 and 1
      cases, respectively. Percutaneous nephrostomy was required in 4 cases before
      definitive treatment. RESULTS: The mean time to development of a lymphocele was
      121 days (range 35 to 631). Symptomatic lymphocele did not require treatment in 3
      patients. Of 19 patients undergoing primary marsupialization, recurrence in 2
      necessitated repeat surgery. However, aspiration and percutaneous drainage proved
      to be definitive in only 2 cases. In total 8 patients required more than 1
      procedure. At a mean followup of 63 months (SD 30.3) 21 allografts continued to
      function with a mean serum creatinine of 152 mumol/l (SD 67.9). In the control
      group 3 patients experienced graft failure and mean serum creatinine was 154
      mumol/l (SD 51.9). Five patients died in the lymphocele group, 2 with functioning
      grafts compared to 4 deaths in the control group. CONCLUSIONS: Surgical
      marsupialization is the preferred primary treatment for symptomatic lymphocele
      and is associated with excellent long-term allograft outcome.

PMID- 16890693
TI  - Laparoscopy versus dorsal lumbotomy for ureteropelvic junction obstruction
      repair.
AB  - PURPOSE: Laparoscopic pyeloplasty offers similar success rates compared to open
      surgery. However, the advanced laparoscopic skills required may limit its
      widespread application. In select patients the dorsal lumbotomy approach can
      provide similar postoperative advantages to minimally invasive surgery. We
      analyze the perioperative management of laparoscopy vs dorsal lumbotomy for the
      repair of ureteropelvic junction obstruction. MATERIALS AND METHODS: In a
      retrospective review 13 patients who underwent dorsal lumbotomy pyeloplasty were
      compared to 19 patients who underwent laparoscopic pyeloplasty between 1998 and
      2003. Preoperative confirmation of obstruction was obtained through excretory
      urogram or renal Lasix scan. All 13 patients undergoing dorsal lumbotomy had a
      dismembered pyeloplasty. Of the 19 laparoscopic cases 16 had a dismembered
      pyeloplasty and 3 had a Fenger procedure. Average followup was 12 months for the
      open group and 13.3 months for the laparoscopic group. Postoperative results were
      evaluated with excretory urogram or renal Lasix scan as well as subjective
      outcomes by the patients. RESULTS: Operative time was slightly longer for the
      laparoscopy group at 231 minutes vs 200 minutes. Estimated blood loss and
      postoperative morphine requirements were also similar. Hospital stay was 3.3 days
      for the dorsal lumbotomy group compared to 2.4 for the laparoscopy group. The
      overall success rate for the laparoscopic group was 94.7% compared to 100% for
      the dorsal lumbotomy group. Each group had 1 complication, paresthesia of
      anterior/medial thigh that resolved by 6 months. CONCLUSIONS: Our preliminary
      results show that a dismembered dorsal lumbotomy pyeloplasty is comparable to
      laparoscopic dismembered pyeloplasty with regard to intraoperative and
      postoperative hospital course.

PMID- 16890694
TI  - Retrospective comparison of retroperitoneal laparoscopic versus open dismembered
      pyeloplasty for ureteropelvic junction obstruction.
AB  - PURPOSE: We evaluated the clinical value of retroperitoneal laparoscopic
      dismembered pyeloplasty for ureteropelvic junction obstruction compared with open
      surgery. MATERIALS AND METHODS: The clinical data of 56 patients who underwent
      retroperitoneal laparoscopic dismembered pyeloplasty were retrospectively
      compared with those of 40 patients who underwent open dismembered pyeloplasty
      through a retroperitoneal flank approach. The Student t test, Pearson chi-square
      test and Mann-Whitney rank sum test were applied for statistical analysis as
      appropriate. RESULTS: Patient demographic data were similar between the 2 groups.
      In the laparoscopic group operative time (80 vs 120 minutes), estimated blood
      loss (10 vs 150 ml), recovery of intestinal function (1 vs 2 days), analgesic
      requirements (diclofenac sodium suppository) (75 vs 150 mg), incision length (3.5
      vs 21 cm) and postoperative hospital stay (7 vs 9 days) were better than in the
      open group (p <0.001 for all). No intraoperative complications occurred in either
      group. The incidence of postoperative complications (2 of 56, 3.6% vs 3 of 40,
      7.5%, p = 0.729) and success rates (55 of 56, 98.2% vs 39 of 40, 97.5%, p =
      0.058) were equivalent in the 2 groups. CONCLUSIONS: Retroperitoneal laparoscopic
      dismembered pyeloplasty is a minimally invasive, safe and effective therapy for
      ureteropelvic junction obstruction with low morbidity, shorter convalescence and
      excellent outcomes, and can be accomplished reasonably quickly in experienced
      hands.

PMID- 16890695
TI  - Erectile dysfunction--an observable marker of diabetes mellitus? A large national
      epidemiological study.
AB  - PURPOSE: We examined whether men with erectile dysfunction are more likely to
      have diabetes mellitus than men without erectile dysfunction, and whether
      erectile dysfunction can be used as an observable early marker of diabetes
      mellitus. MATERIALS AND METHODS: Using a nationally representative managed care
      claims database from 51 health plans and 28 million members in the United States,
      we conducted a retrospective cohort study to compare the prevalence rates of
      diabetes mellitus between men with erectile dysfunction (285,436) and men without
      erectile dysfunction (1,584,230) during 1995 to 2001. Logistic regression models
      were used to isolate the effect of erectile dysfunction on the likelihood of
      having diabetes mellitus with adjustment for age, region and 7 concurrent
      diseases. RESULTS: The diabetes mellitus prevalence rates were 20.0% in men with
      erectile dysfunction and 7.5% in men without erectile dysfunction. With
      adjustment for age, region and concurrent diseases, the odds ratio of having
      diabetes mellitus between men with erectile dysfunction and without erectile
      dysfunction was 1.60 (p <0.0001). With adjustment for regions and concurrent
      diseases, the age specific odds ratios ranged from 2.94 (p <0.0001, age 26 to 35)
      to 1.05 (p = 0.1717, age 76 to 85). CONCLUSIONS: Men with erectile dysfunction
      were more than twice as likely to have diabetes mellitus as men without erectile
      dysfunction. Erectile dysfunction is an observable marker of diabetes mellitus,
      strongly so for men 45 years old or younger and likely for men 46 to 65 years
      old, but it is not a marker for men older than 66 years.

PMID- 16890697
TI  - Neurological bypass for sensory innervation of the penis in patients with spina
      bifida.
AB  - PURPOSE: Most male patients with spina bifida have normal sexual desires. During
      puberty they begin to realize that they can achieve erection and sexual
      intercourse but without any sensation in the penis. We hypothesized that restored
      sensation in the penis would greatly contribute to their quality of life and
      sexual health. In this prospective study we investigated the outcome of a new
      operative neurological bypass procedure in patients with spina bifida. MATERIALS
      AND METHODS: In 3 patients who were 17, 18 and 21 years old with a spinal lesion
      at L5, L4 and L3-L4, respectively, the sensory ilioinguinal nerve (L1) was cut
      distal in the groin and joined by microneurorrhaphy to the divided ipsilateral
      dorsal nerve of the penis (S2-4) at the base of the penis. All patients underwent
      preoperative and postoperative neurological and psychological evaluations.
      RESULTS: By 15 months postoperatively all patients had achieved excellent
      sensation on the operated side of the glans penis. They were unequivocally
      positive about the results and the penis had become more integrated into the body
      image. In 2 patients masturbation became more meaningful and 1 became more
      sexually active with and without his partner. CONCLUSIONS: The newly designed
      neurological bypass procedure in patients with spina bifida resulted in excellent
      sensibility in the glans penis. The new sensation appeared to contribute to the
      quality of the patient sexuality and sexual functioning as well as to the feeling
      of being a more normal and complete individual who is more conscious of the
      penis. This new operation might become standard treatment in patients with spina
      bifida in the future.

PMID- 16890699
TI  - Cost trends for oncological renal surgery: support for a laparoscopic standard of
      care.
AB  - PURPOSE: There may be inherent costs associated with the cultivation of
      laparoscopic expertise. We compared the cost trends for laparoscopy during the
      development of our program with that of open surgery for renal neoplasms.
      MATERIALS AND METHODS: We retrospectively reviewed the records of 381 patients
      treated surgically for renal cortical neoplasms from 1998 to 2003. Demographic
      information and cancer specific data were recorded on each subject. Direct
      variable costs, which are directly traceable to the patient care service provided
      and vary with patient volume, were used to analyze cost. Temporal trends were
      assessed using multivariate models developed to determine smoothed mean costs by
      year. RESULTS: Although it was initially more expensive, by 2003 mean costs were
      lower for laparoscopic than for open radical nephrectomy ($5,157 vs $5,808). This
      reflected a significantly lower annual increase in direct variable costs for
      laparoscopy vs open surgery even after adjustment for patient age, sex, race and
      clinical stage (p = 0.013). Although a similar trend was observed when comparing
      nephron sparing procedures vs open surgery, this did not attain statistical
      significance. In addition to surgical technique, only higher clinical stage was
      independently associated with increased direct variable costs after adjustment
      for operative year (p <0.0001). CONCLUSIONS: Relative to their open counterparts
      the costs of laparoscopic treatment of renal cortical neoplasms have increased at
      a lower rate in the last 6 years. When considered in the context of the well
      established benefits of laparoscopy, our findings lend additional support in
      favor of laparoscopy as the standard of care.

PMID- 16890701
TI  - Laparoscopy for renal cell carcinoma: diffusion versus regionalization?
AB  - PURPOSE: Recognizing the emergence of laparoscopy as a standard of care for
      surgical treatment in many patients with organ confined renal cell carcinoma, we
      explored the diffusion of this technology by examining temporal trends in the
      nationwide use of laparoscopic total and partial nephrectomy in patients with
      renal cell carcinoma. MATERIALS AND METHODS: Data from the Healthcare Cost and
      Utilization Project Nationwide Inpatient Sample were abstracted for 1991 through
      2003. International Classification of Diseases-Ninth Revision, Clinical
      Modification 9 codes were used to identify patients undergoing open and
      laparoscopic total and partial nephrectomy for renal cell carcinoma. Using
      hospital sampling weights we calculated annual incidence rates for open and
      laparoscopic nephrectomy, thereby estimating the diffusion of laparoscopy.
      Bivariate and multivariate analyses were used to identify patient and hospital
      characteristics associated with the more frequent use of laparoscopic techniques.
      RESULTS: Data on 63,812 patients were abstracted from the Nationwide Inpatient
      Sample, yielding a weighted national estimate of 323,979 who underwent
      laparoscopic (4.9%) or open (95.1%) nephrectomy (total or partial) for renal cell
      carcinoma between 1991 and 2003. Although it is still infrequent, the use of
      laparoscopy has increased steadily since 1998 with a utilization peak in 2003 of
      1.7 laparoscopic nephrectomies per 100,000 American population, representing 16%
      of all total and partial nephrectomies for renal cell carcinoma in 2003.
      Treatment year, overall hospital nephrectomy volume and teaching hospital status
      were the most robust determinants of increased laparoscopic use (each p <0.001).
      CONCLUSIONS: Although its use has increased progressively in the last decade, the
      dissemination of laparoscopy for renal cell carcinoma has been generally slow and
      limited in scope. The next step in this body of work is to identify specific
      technical, educational and policy interventions that will influence the diffusion
      of this alternative standard of care.

PMID- 16890703
TI  - Sexual behavior, sexually transmitted diseases and prostatitis: the risk of
      prostate cancer in black men.
AB  - PURPOSE: Black men are diagnosed with prostate cancer more often than white men,
      present with more advanced disease and have worse stage specific survival. Given
      the high risk of incidence and mortality in this population, determining
      potentially modifiable factors is important. Recent studies have suggested a link
      between chronic inflammation and development of prostate cancer. In concurrence,
      population based studies of white men have revealed an increased risk of prostate
      cancer with history of sexually transmitted diseases and prostatitis. MATERIALS
      AND METHODS: We explored the chronic inflammation hypothesis of prostate cancer
      development among black men by examining sexual activity, sexually transmitted
      diseases and prostatitis in a population based study of 129 patients and 703
      controls 40 to 79 years old. RESULTS: After adjusting for age, income, cigarette
      smoking, and history of digital rectal examination and prostate specific antigen
      tests in the last 5 years, we observed that a history of gonorrhea infection and
      prostatitis increased the odds of prostate cancer 1.78-fold (95% CI 1.13, 2.79)
      and 4.93-fold (95% CI 2.79, 8.74), respectively. Men reporting 25 or more sexual
      partners were 2.80 (95% CI 1.29, 6.09) times more likely to be diagnosed with
      cancer compared to men with 5 or fewer partners. CONCLUSIONS: Our findings
      support the significance of prior sexual practices, exposure to sexually
      transmitted microbial agents and history of prostatic infection in the natural
      history of prostate cancer in black men. Additional prospective research
      incorporating serological markers of infectious agents or predictive markers of
      chronic inflammation should serve to elucidate the possible causal pathway of
      recurring or persistent infection in the etiology of prostate cancer in black
      men.

PMID- 16890704
TI  - Is race a positive predictor of cancer on repeat prostate biopsy?
AB  - PURPOSE: High grade intraepithelial neoplasia and atypical small acinar
      proliferation increase the probability of cancer on a subsequent prostate biopsy.
      We investigated whether race is prognostic for detecting cancer in patients
      undergoing repeat prostate biopsies. MATERIALS AND METHODS: At a single
      institution 416 men underwent 2 or more prostate biopsies from January 1993
      through June 2003 for a total of 1,023 biopsies. We retrospectively examined
      multiple factors, including patient age, race, total number of biopsy cores total
      number of previously negative biopsy cores, prostate specific antigen, prostate
      specific antigen slope, digital rectal examination and family history of prostate
      cancer. Previous high grade intraepithelial neoplasia, atypical small acinar
      proliferation and Gleason score in positive biopsies were recorded from the
      histopathology review. Clinical variables were compared between black and white
      men using the Wilcoxon rank sum and Fisher exact tests. The Cox proportional
      hazards model was used for multivariate analysis. RESULTS: Of the 416 men 216
      (51.9%) were black, 174 (41.8%) were white and 26 (6.3%) were another race. The
      average number of biopsy sessions in black and white men was 2.41 and 2.51,
      respectively. The cancer detection rate was 35.1% at the second biopsy, 34.6% at
      the third biopsy and 32.0% at the fourth biopsy. Cancer was diagnosed in 43.5% of
      black men compared to 25.9% of white men (p = 0.0004). When clinical and
      pathological variables were compared between the racial groups, black men had
      significantly higher prostate specific antigen (p = 0.02). There was no
      statistically significant difference in patient age, total number of cores,
      number of previous negative cores, prostate specific antigen slope, abnormal
      digital rectal examination, family history, or previous high grade
      intraepithelial neoplasia or atypical small acinar proliferation. Multivariate
      analysis showed that race approached but did not achieve statistical significance
      as a predictor of prostate cancer on repeat biopsy (p = 0.09). Previous high
      grade intraepithelial neoplasia (p = 0.0025), previous atypical small acinar
      proliferation (p = 0.0049), digital rectal examination (p = 0.0076) and prostate
      specific antigen slope (p = 0.0005) were independent predictors of prostate
      cancer on repeat biopsy. Of patients with previous atypical small acinar
      proliferation black men had a significantly higher rate of cancer detection on
      repeat biopsy. CONCLUSIONS: Previous high grade intraepithelial neoplasia,
      atypical small acinar proliferation, digital rectal examination and prostate
      specific antigen slope were independent predictors of prostate cancer on repeat
      biopsy. Race approached but did not attain significance after adjusting for
      disease features.

PMID- 16890705
TI  - Impact of familial and hereditary prostate cancer on cancer specific survival
      after radical retropubic prostatectomy.
AB  - PURPOSE: Men with a family history of prostate cancer are at higher risk for
      prostate cancer. There are conflicting data regarding the impact of hereditary
      forms of prostate cancer on long-term outcomes after radical prostatectomy. We
      examined the impact of familial and hereditary prostate cancer treatment in the
      prostate specific antigen era. MATERIALS AND METHODS: Patients who underwent
      radical prostatectomy for prostate cancer from 1987 to 1997 were surveyed (3,560
      responders) to determine the family history of prostate cancer. Patients were
      categorized as having familial prostate cancer if they had at least 1 first
      degree relative with prostate cancer. Hereditary prostate cancer was defined as
      nuclear families with 3 cases of prostate cancer, families with prostate cancer
      in each of 3 generations and families with 2 men diagnosed before age 55 years.
      Sporadic prostate cancer was defined as patients with no family history. Clinical
      and pathological features, and long-term outcome measures, including biochemical
      recurrence-free, systemic progression-free and cancer specific survival, were
      compared among patients with familial, hereditary and sporadic prostate cancer.
      RESULTS: A total of 865 and 133 patients were categorized as having familial
      prostate cancer and hereditary prostate cancer, respectively. Preoperatively
      prostate specific antigen was higher in patients with hereditary prostate cancer
      than in the other 2 groups (p = 0.04). Ten-year biochemical progression-free,
      systemic progression-free and cancer specific survival were equivalent.
      CONCLUSIONS: Except for preoperative prostate specific antigen,
      clinicopathological features and long-term oncological outcomes are equivalent
      after radical prostatectomy in patients with familial, hereditary and sporadic
      prostate cancer.

PMID- 16890706
TI  - An improved approach to followup care for the urological patient: drop-in group
      medical appointments.
AB  - PURPOSE: To increase prompt access to routine office visits the concept of the
      group appointment was developed in the primary care setting. Drop-in group
      medical appointments have been piloted at our department. We hypothesized that 1)
      efficiency could be improved by seeing 6 to 14 patients at 1 appointment, 2)
      access to appointment times would increase and 3) patient satisfaction would be
      enhanced with 60 minutes of didactic contact and discussion with the urologist.
      MATERIALS AND METHODS: Patients were invited to participate in a drop-in group
      medical appointment. Appointments were made based on sex and not on diagnosis. A
      60-minute group teaching session was followed by a private 2 to 5-minute physical
      examination or further testing, as indicated. Confidential satisfaction surveys
      were administered to drop-in group medical appointment participants and patients
      seen at traditional individual (solo) appointments. Results were compared.
      RESULTS: From September 22, 2003 to August 30, 2004, 279 patients attended a drop
      in group medical appointment. Mean patient age was 63 years and 142 patients were
      65 years or older. Most diagnoses were prostate cancer, erectile dysfunction,
      benign prostatic hyperplasia, incontinence, neurogenic bladder and chronic
      discomfort syndromes. Of the patients 287 were surveyed, including 177 at drop-in
      group medical appointments and 110 at solo appointments. Patient satisfaction
      with the drop-in group medical appointment format was as high as that of solo
      patients with 87% of drop-in group medical appointment patients rating their
      experience as excellent or very good vs 88% by solo patients. CONCLUSIONS: Drop
      in group medical appointments can be implemented successfully in a urological
      practice with high patient satisfaction despite the sensitive nature of topics
      discussed. Ideal patients are those with chronic or complex conditions and those
      requiring repetitive discussions, such as elderly individuals.

PMID- 16890708
TI  - Evidence-based medicine: a survey of American Urological Association members.
AB  - PURPOSE: We investigated the attitudes and opinions of urologists toward evidence
      based medicine. MATERIALS AND METHODS: In April of 2005 we contacted members of
      the American Urological Association listed with an e-mail address to participate
      in a web based survey. Participants were asked to characterize their level of
      agreement with statements referring to the role of evidence-based medicine in
      urology, to indicate their level of understanding of 15 evidence-based medicine
      related terms and to report their familiarity with 6 evidence-based medicine
      related resources. RESULTS: Of 8,100 American Urological Association members 714
      (8.8%) responded to this survey. There was widespread agreement (median score 9)
      with the concept that evidence-based medicine improves patient care and that
      every urologist should be familiar with critical appraisal techniques. Select
      terms such as median/mean, selection bias and type I error were well understood
      ("understand and could explain to others") by 86%, 57% and 17%, respectively. The
      American Urological Association Best Practice Guidelines were the single best
      known resource that 91% of respondents reviewed or used regularly. CONCLUSIONS:
      To our knowledge this survey represents the first evidence-based medicine survey
      of a large international group of urologists. Its results indicate that evidence
      based medicine is viewed favorably and that the American Urological Association
      Best Practice Guidelines present a well accepted instrument for the dissemination
      of evidence-based medicine in urology. However, given the low response rate and
      the potential for selection bias, interpretation of these results must be
      performed with caution. Future efforts should be directed toward providing
      increased opportunities for urologists to learn the principles of critical
      appraisal, facilitating the application of evidence-based medicine in the
      community and promoting high quality research.

PMID- 16890709
TI  - Long-term followup of patients after redo bladder neck reconstruction for bladder
      exstrophy complex.
AB  - PURPOSE: The aim of this study was to determine whether redo bladder neck
      reconstruction is effective in achieving continence after a failed bladder neck
      reconstruction procedure. MATERIALS AND METHODS: We retrospectively reviewed the
      hospital records of patients with bladder exstrophy who had undergone redo
      bladder neck reconstruction. There were 30 patients in the study, including 20
      boys and 10 girls. Mean patient age at redo bladder neck reconstruction was 9.3
      years (range 3.2 to 15.5). The patients were divided into 3 groups on the basis
      of the preoperative pattern of incontinence--incomplete wetters, complete wetters
      and those on continuous suprapubic drainage. Of the patients 15 already had
      undergone bladder augmentation, 12 had undergone a Mitrofanoff procedure and 12
      had been treated with bulking agents injected in the bladder neck in an attempt
      to achieve continence. Four patients had undergone more than 1 bladder neck
      procedure. The patients were investigated with a combination of noninvasive
      urodynamics, cystoscopy, cystogram and ultrasound. All patients underwent
      Mitchell's modification of Young-Dees-Leadbetter bladder neck reconstruction.
      Additional procedures performed included augmentation cystoplasty and Mitrofanoff
      formation. RESULTS: Mean followup was 6.9 years (range 1.2 to 15.5).
      Postoperatively 28 patients were using clean intermittent catheterization to
      empty the bladder (5 per urethra, 23 via Mitrofanoff). Two patients remained on
      continuous suprapubic catheter drainage. A total of 18 patients (60%) were dry
      postoperatively (80% of girls and 50% of boys). Among dry patients only 3 were
      performing clean intermittent catheterization per urethra and 15 via a
      Mitrofanoff channel. No patient was able to void per urethra without the need for
      clean intermittent catheterization. The 2 patients on continuous suprapubic
      catheter drainage continued to remain so. At night only 50% of the patients were
      dry (5 on free drainage, 4 on clean intermittent catheterization, 6 not on any
      drainage). Those patients who did not respond satisfactorily to redo bladder neck
      reconstruction underwent subsequent additional procedures, which included
      injection of bulking agents (3 patients), insertion of an artificial urinary
      sphincter (1), Mitrofanoff formation (2) and bladder augmentation plus
      Mitrofanoff channel (1). Postoperative complications included difficulty with
      clean intermittent catheterization (8 patients), perivesical leak (1), recurrent
      epididymo-orchitis (1), upper urinary tract dilatation (2) and incisional hernia
      (1). Bladder neck closure was being considered in 5 patients. CONCLUSIONS: In our
      experience redo bladder neck reconstruction cannot achieve continence with
      volitional voiding per urethra. Although redo bladder neck reconstruction can
      render a significant number of patients dry, it is only effective if performed in
      conjunction with augmentation. Failure of the initial bladder neck reconstruction
      may be a reflection of a bladder that is of inadequate capacity and/or
      compliance. Therefore, bladder augmentation should be considered in all patients
      requiring redo bladder neck reconstruction. Bladder neck closure may be a better
      alternative to redo bladder neck reconstruction.

PMID- 16890711
TI  - Calcification of glutaraldehyde cross-linked collagen in bladder neck injections
      in children with incontinence: a long-term complication.
AB  - PURPOSE: We report the incidence of calcifications developing at the bladder
      neck/urethra in pediatric patients treated with glutaraldehyde cross-linked
      collagen for urinary incontinence. MATERIALS AND METHODS: We reviewed charts of
      patients treated with glutaraldehyde cross-linked collagen injections for urinary
      incontinence between 1994 and 1999. Etiology of incontinence, pertinent medical
      history, operative details and postoperative imaging were examined. RESULTS: Of
      31 patients 4 (13%) had development of submucosal calcifications in the bladder
      neck/urethra. All 4 patients had received multiple injections of glutaraldehyde
      cross-linked collagen for incontinence secondary to neurogenic bladder. The
      calcifications were confirmed surgically. Pathology reports available for 2 of 4
      patients showed chronic inflammation without dysplasia or malignant changes. Mean
      followup was significantly different between calcified and noncalcified cases
      (10.3 vs 7.2 years, p = 0.009), as was total volume of collagen injected (21 vs
      12 cc, p = 0.012). Mean time to diagnosis of calcifications was 8.8 years (range
      7 to 11) after first injection. A total of 24 patients without calcification
      underwent bladder imaging at a mean of 6.8 years (+/-2.2) after glutaraldehyde
      cross-linked collagen injection, which was not significantly different than the
      time to diagnosis (p = 0.089). The number of injections was not significantly
      different between the 2 groups (p = 0.426). CONCLUSIONS: Of our patients 13% had
      development of calcifications at the site of prior glutaraldehyde cross-linked
      collagen injections for incontinence. These calcifications were surrounded by
      chronic inflammation. Patients who have undergone glutaraldehyde cross-linked
      collagen injections may benefit from long-term followup with bladder imaging to
      detect and follow calcifications at prior injection sites.

PMID- 16890713
TI  - Abnormal circadian rhythm of diuresis or nocturnal polyuria in a subgroup of
      children with enuresis and hypercalciuria is related to increased sodium
      retention during daytime.
AB  - PURPOSE: In a subgroup of children with enuresis an increase in nighttime water
      and solute excretion has been documented. To investigate if modifications in
      renal function are involved in nocturnal enuresis, we assessed circadian
      variation in natriuresis and tubular sodium handling in polyuric hypercalciuric
      children. MATERIALS AND METHODS: A total of 10 children with proved
      hypercalciuria and nocturnal polyuria and 10 age matched controls were included
      in the study. A 24-hour urine collection was performed in 8 sampling periods for
      measurement of urinary sodium excretion. Segmental tubular sodium transport was
      investigated during a daytime oral water load test and calculated according to
      standardized clearance methodology. RESULTS: The children with enuresis showed a
      marked increase in the fractional excretion of sodium during the night (0.93% +/-
      0.36%), while daytime sodium excretion was decreased (0.84% +/- 0.23%). Analysis
      of segmental tubular sodium transport revealed decreased delivery of sodium to
      distal tubule (C(H2O) + C(Na) = 10.7 ml/100 ml glomerular filtration rate),
      indicating increased proximal tubular sodium reabsorption but also stimulation of
      distal sodium reabsorption as demonstrated by increased fractional distal sodium
      reabsorption (92.9% +/- 2.2%, controls 90.5% +/- 2.9%). Increased distal
      reabsorption was associated with increased fractional potassium excretion (17.5%
      +/- 2.7%, controls 13.6% +/- 6.4%), indicating increased distal tubular
      sodium/potassium exchange. CONCLUSIONS: No intrinsic defect in renal tubular
      sodium transport was found, but during the day increased sodium reabsorption in
      proximal and distal tubules was observed, suggesting extrarenal factors to be
      involved in altered circadian variation in solute and water excretion by the
      kidney.

PMID- 16890714
TI  - Renal and bladder functional status at diagnosis as predictive factors for the
      outcome of primary vesicoureteral reflux in children.
AB  - PURPOSE: We studied the relationship between renal and bladder functional status
      at diagnosis and spontaneous resolution of reflux in young children with primary
      vesicoureteral reflux. MATERIALS AND METHODS: Children with grade III or greater
      vesicoureteral reflux were recruited for the study. At entry each patient
      underwent voiding cystourethrogram, renal ultrasound, isotope renogram, and
      natural filling and conventional filling urodynamic studies. Patients were then
      divided into 4 groups-group 1 had normal renal and bladder function, group 2 had
      abnormal renal and normal bladder function, group 3 had normal renal and abnormal
      bladder function, and group 4 had abnormal renal and bladder function.
      Correlation between renal and bladder functional status with reflux resolution at
      a minimum followup of 24 months was evaluated. RESULTS: A total of 82 patients
      (mean age 3.8 years) were prospectively evaluated and followed. There were 18
      patients (13 males and 5 females) in group 1, 19 (13 and 6) in group 2, 19 (18
      and 1) in group 3 and 26 (22 and 4) in group 4. Complete resolution of
      vesicoureteral reflux occurred in 17 patients (94%) in group 1 and 7 (37%) in
      group 2. None of the patients from group 3 or group 4 achieved complete
      vesicoureteral reflux resolution. Reflux grade remained unchanged in 15 patients
      (79%) in group 3 and 20 (77%) in group 4. CONCLUSIONS: Resolution of
      vesicoureteral reflux significantly correlated with renal and bladder functional
      status at diagnosis. Normal renal and bladder function at diagnosis is highly
      predictive of complete resolution of vesicoureteral reflux, whereas abnormal
      renal and bladder function is prognostic for persistence of reflux.

PMID- 16890716
TI  - Salvage extravesical ureteral reimplantation after failed endoscopic surgery for
      vesicoureteral reflux.
AB  - PURPOSE: Open intravesical ureteral reimplantation has been reported to be
      uncomplicated following dextranomer/hyaluronic acid implantation. However, there
      are no known reports regarding extravesical ureteral reimplantation following
      dextranomer/hyaluronic acid failure. We reviewed our experience with extravesical
      ureteral reimplantation after dextranomer/hyaluronic acid failure. MATERIALS AND
      METHODS: We reviewed the charts of 30 patients who underwent extravesical
      ureteral reimplantation after dextranomer/hyaluronic acid failure. If reflux was
      initially bilateral and only a unilateral cure was achieved, the cured ureter was
      not reimplanted. Intraoperative complications, need for stenting or prolonged
      bladder catheterization, length of hospitalization and radiographic results were
      noted. RESULTS: At cystoscopy the dextranomer/hyaluronic acid implants were not
      seen in half of the patients. In the remaining 15 patients the blebs had moved
      caudally and/or were seen extravesically at the ureteral hiatus or along
      Waldeyer's sheath. Unilateral extravesical ureteral reimplantation was performed
      without difficulty in all patients and there were no intraoperative
      complications. Stents were left indwelling only in those patients who had
      undergone dismembered ureteral reimplantation. No patient required prolonged
      bladder drainage. All patients except 2 who had undergone additional procedures
      were discharged home within 24 hours postoperatively. There was no evidence of
      obstruction on postoperative renal sonography, and extravesical ureteral
      reimplantation was confirmed to be successful in all 24 patients with
      postoperative voiding cystourethrograms. CONCLUSIONS: Extravesical ureteral
      reimplantation can be performed without difficulty following
      dextranomer/hyaluronic acid implantation. Since extravesical ureteral
      reimplantation is less morbid and better tolerated than intravesical
      reimplantation, it is an excellent treatment option for patients with persistent
      unilateral vesicoureteral reflux following dextranomer/hyaluronic acid
      implantation. Furthermore, in cases in which vesicoureteral reflux is initially
      bilateral our data suggest that reimplantation of the successfully treated
      contralateral ureter can be avoided.

PMID- 16890717
TI  - The timing of primary neurosurgical repair significantly affects neurogenic
      bladder prognosis in children with myelomeningocele.
AB  - PURPOSE: The correlation between timing of the primary neurosurgical repair and
      urological prognosis in infants with open spinal dysraphism remains unknown. We
      investigated the impact of primary repair timing on neurogenic bladder prognosis
      in children with myelomeningocele. MATERIALS AND METHODS: We retrospectively
      reviewed the records of 401 children with myelomeningocele followed at our
      multidisciplinary clinic between 1996 and 2005. Among these patients 129 were
      included in the study based on the availability of urological followup data at
      age 3 years, which was chosen as an ideal point for the standardization of
      urological findings. Children were assigned to 1 of 2 groups-those who underwent
      primary neurosurgical repair within 72 hours of delivery (group 1) and those
      undergoing repair after 72 hours (group 2). We compared the incidence of febrile
      urinary tract infections, hydronephrosis, vesicoureteral reflux and secondary
      tethering of the spinal cord at age 3 years, as well as cystometric bladder
      capacity and detrusor leak point pressure between the 2 groups. RESULTS:
      Urological followup data at age 3 years revealed significantly increased
      incidence of febrile urinary tract infections, vesicoureteral reflux,
      hydronephrosis and secondary tethering of the spinal cord in children in group 2
      compared to group 1 (chi-square, p < or =0.05 for all comparisons). Urodynamic
      assessment also showed a significantly lower bladder capacity and a substantially
      higher detrusor leak point pressure in children who received primary repair at
      later than 72 hours (t test, p <0.05). A subgroup analysis of group 1 comparing
      children who underwent repair before and after 24 hours following delivery failed
      to demonstrate any significant difference in terms of febrile urinary tract
      infections, vesicoureteral reflux, hydronephrosis and secondary tethering (chi
      square, p >0.05 for all comparisons), whereas mean bladder capacity was
      significantly higher (t test, p <0.05) and mean detrusor leak point pressure was
      lower (t test, p = 0.08) in children undergoing repair within 24 hours of
      delivery. CONCLUSIONS: The timing of primary neurosurgical repair has a
      significant impact on neurogenic bladder prognosis in children with
      myelomeningocele. Closure of the spinal lesion on the first day of life seems to
      provide the best chance for favorable lower urinary tract function.

PMID- 16890718
TI  - Reevaluation of the fetal muscle development of the vesical trigone.
AB  - PURPOSE: Fetal development of the interureteral muscle, a precondition of a
      sufficient opposite anchoring of the ureterovesical junction, and the muscle
      architecture of the bladder neck was investigated using immunohistochemical
      analysis. MATERIALS AND METHODS: We investigated the ureterotrigonal units in 38
      fetal specimens (16 females, 22 males) and 7 newborns (2 females, 5 males) at 9
      to 40 weeks of gestation. Histology was based on serial consecutive sections of
      the bladder base. Anti-human alpha-smooth muscle actin immunostaining was used to
      demonstrate the time course of muscle development and arrangement. RESULTS: A
      much earlier developmental stage of the trigone muscle configuration during fetal
      life was noted than has been reported to date. The condensation of myoblasts
      located mainly in the dorsal wall of the trigone and at the bladder outlet was
      present beginning at 12 weeks of gestation. The trigone develops continuously as
      a single circular muscular layer corresponding to the posterior part of the
      vesical sphincter muscle. Muscle fibers forming the interureteral junction were
      demonstrable beginning at 14 weeks of gestation. CONCLUSIONS: There is a close
      connection between the trigonal smooth muscle layer and the vesical sphincter
      muscle forming the main part of the trigone by 12 weeks of gestation. Fetal
      development of the trigone, in particular the muscle architecture of the bladder
      neck, which consists of only a ring-shaped muscular layer, and the transverse
      oriented interureteral muscle results in a functional entity representing the
      anatomical basis for a competent ureterovesical junction.

PMID- 16890719
TI  - Reproducibility of contrast enhanced magnetic resonance renography in
      adolescents.
AB  - PURPOSE: We sought to determine the reproducibility of magnetic resonance imaging
      renography using 3 different mathematical models and 2 different approaches to
      convert the relative signal intensity into quantitative indices. Furthermore, we
      wanted to examine the influence of fluid intake on the obtained renal parameters.
      MATERIALS AND METHODS: A total of 10 healthy volunteers 13 to 16 years old were
      subjected to magnetic resonance imaging 3 times within 10 weeks, including an
      examination where fluid intake was increased. At each examination 0.1 mmol/kg
      gadolinium diethylenetriamine pentaacetic acid was administrated intravenously as
      a rapid bolus during a fast magnetic resonance renography sequence. Images were
      acquired in the coronal plan, and 1,200 images were recorded during approximately
      7 minutes. Cortical data were analyzed to estimate absolute and differential
      function of renal parameters by converting signal intensities into quantitative
      units. RESULTS: Using the simple approach that a change in magnetic resonance
      imaging signal is linearly related to the change in gadolinium diethylenetriamine
      pentaacetic acid concentration, we found reproducibility in the range of 1% to 5%
      of all estimations of the differential renal function. The relative glomerular
      ultrafiltration (ml per minute per cm(3) kidney cortex) was calculated and a
      reproducibility of 7% was observed for relative glomerular ultrafiltration (using
      the model based on deconvolution). Increased hydration caused a significant
      change in most parameters. CONCLUSIONS: Contrast enhanced magnetic resonance
      renography is reproducible in the normal human kidney but excessive water intake
      has a significant influence on these parameters. Further studies are required to
      elucidate whether similar measurements can be applied to a kidney with impaired
      function.

PMID- 16890721
TI  - Orchiopexy practice patterns in New York State from 1984 to 2002.
AB  - PURPOSE: Cryptorchidism is the most common genital anomaly identified at birth,
      and endocrine disrupters in the environment may be causing an increase in this
      entity. To determine whether the rate of surgery for undescended testes is
      increasing, we evaluated all documented orchiopexies performed in New York State
      during a 19-year period. MATERIALS AND METHODS: We used the New York State
      Statewide Planning and Research Cooperative System database to identify all
      orchiopexies performed between 1984 and 2002. Orchiopexies performed for torsion
      were excluded. RESULTS: A total of 36,484 boys were included in the study, of
      whom 26,575 were outpatients and 9,909 were inpatients. The overall rate of
      orchiopexy in our population (number of orchiopexies performed divided by number
      of live births during the study period) was 1.39%, and remained fairly constant
      throughout the study. Most orchiopexies were performed on an inpatient basis
      early in the study (92% in 1984) but by 2002 only 3% of repairs were done in
      inpatients. Early in the study (1984 to 1988) only 20% of orchiopexies were
      performed in patients younger than 2 years. However, between 1999 and 2002, 37.8%
      of orchiopexies were done before age 2. CONCLUSIONS: Orchiopexy is being
      performed at an earlier age today than 2 decades ago. However, the majority of
      orchiopexies are not performed until after the recommended patient age of 2
      years. The rate of orchiopexy is substantially higher than the accepted rate of
      0.8% to 1.1%. Delayed referral to a surgeon, repair of retractile testicles and
      truly ascending testicles may account for these findings.

PMID- 16890720
TI  - Laparoscopic transperitoneal nephrectomy is feasible in the first year of life
      and is not affected by kidney size.
AB  - PURPOSE: We analyzed the feasibility of laparoscopic nephroureterectomy in
      children younger than 1 year, with regard to size of impaired kidney. MATERIALS
      AND METHODS: A total of 40 consecutive children underwent transperitoneal
      laparoscopic nephrectomy during a 4-year period. Of the patients 19 (48%) were
      younger than 1 year and were analyzed in detail. Nine of these patients (47.4%)
      had a multicystic dysplastic kidney, 9 (47.4%) had reflux nephropathy and 1
      (5.3%) had obstructive nephropathy. The duration of operation, reasons for
      conversion, and intraoperative and postoperative complications were prospectively
      documented. RESULTS: Mean operative time was 133 minutes (range 60 to 240), and
      did not differ significantly between patients up to age 12 months compared to
      children 1 year and older (126 vs 148 minutes, NS). Nephroureterectomy was
      completed laparoscopically in 17 of 19 children (89%) up to age 12 months vs 20
      of 21 (95%) 1 year and older (NS). In 1 child younger than 1 year suture
      dislocation at the renal artery required laparoscopic resuturing. No further
      complications were seen. In children younger than 1 year the mean operating time
      was not significantly different for resection of multicystic dysplastic kidney (8
      patients, 113 minutes) compared to reflux nephropathy (9, 134 minutes, NS). Mean
      operating time did not differ significantly for kidney volumes less than 10 cc (8
      patients, 119 minutes) compared to kidney volumes greater than 10 cc (9, 129
      minutes, NS). CONCLUSIONS: The feasibility of transperitoneal laparoscopic
      nephroureterectomy in children younger than 1 year is excellent. The duration of
      operation is not affected by patient age, underlying disease or kidney size.

PMID- 16890722
TI  - Myelolipoma.

PMID- 16890723
TI  - Renal artery embolus treated with urokinase perfusion.

PMID- 16890725
TI  - Interleukin-21 gene transfection into mouse bladder cancer cells results in tumor
      rejection through the cytotoxic T lymphocyte response.
AB  - PURPOSE: We developed the genetically modified mouse bladder carcinoma MBT2
      (American Type Culture Collection, Manassas, Virginia), which secretes
      interleukin-21, to investigate the functional activities of interleukin-21 in
      tumor immunity. MATERIALS AND METHODS: The IL-21 gene was cloned from activated T
      cells by reverse transcriptase-polymerase chain reaction, inserted into an
      expression vector and then introduced into MBT2 using Lipofectamine. Exogenous
      interleukin-21 was assayed in culture supernatants from transfectants using
      sandwich enzyme-linked immunoassay. Direct antitumor and tumor vaccine effects
      were investigated in syngeneic mice rendered immunodeficient by administration of
      the corresponding antibody. RESULTS: MBT2 cells secreting interleukin-21 (MBT2/IL
      21) were completely rejected when subcutaneously injected into syngeneic mice.
      MBT2/IL-21 proliferated only when CD8+ T cells were depleted, whereas MBT2/IL-21
      proliferation was totally abrogated in mice depleted of CD4+ T cells, natural
      killer cells or interferon-gamma. Subcutaneous injection of MBT2/IL-21 treated
      with mitomycin C remarkably inhibited parental MBT2 tumor growth at the
      contralateral site. Cytotoxicity assays using splenocytes from mice that rejected
      MBT2/IL-21 and the immunohistochemical features of MBT2/IL-21 tumors confirmed
      that in situ production of interleukin-21 can elicit powerful antitumor activity
      through CD8+ T-cell activation. CONCLUSIONS: Interleukin-21 production in situ
      elicits antitumor activity through the activation of CD8+ T cells in vivo.

PMID- 16890724
TI  - Protective effects of plasma carotenoids on the risk of bladder cancer.
AB  - PURPOSE: We examined the associations between plasma micronutrients and bladder
      cancer risk, and evaluated the combined effects of carotenoid and cigarette
      smoke. MATERIALS AND METHODS: We performed a case-control study in 242 patients
      with bladder cancer and 204 healthy controls at Memorial Sloan-Kettering Cancer
      Center from 1993 to 1997. Epidemiological data and blood specimens were collected
      on 84 cases and 173 controls. Plasma micronutrients, including lutein,
      zeaxanthin, beta-cryptoxanthin, lycopene, alpha-carotene, beta-carotene, retinol,
      alpha-tocopherol and gamma-tocopherol, were determined by high performance liquid
      chromatography. The logistic regression model was used to estimate the effects
      from carotenoid, tocopherol and retinol on the risk of bladder cancer. RESULTS:
      Based on quartiles of plasma micronutrient levels and continuous variables,
      adjusted ORs were estimated for bladder cancer after controlling for potential
      confounders, including patient age, sex, education and pack-years of smoking.
      When using plasma levels of micronutrients as continuous variables, the adjusted
      OR was 0.22 (95% CI 0.05 to 0.92) for alpha-carotene, 0.42 (95% CI 0.18 to 1.00)
      for lutein, 0.16 (95% CI 0.02 to 1.06) for zeaxanthin, 0.94 (95% CI 0.89 to 0.99)
      for lycopene and 0.90 (95% CI 0.81 to 1.00) for beta-cryptoxanthin. The adjusted
      OR for the joint effect of plasma carotenoids and tobacco smoking was 6.22 (95%
      CI 1.87 to 20.8) in smokers with lower lutein and 5.18 (95% CI 1.57 to 17.1) in
      smokers with lower zeaxanthin. CONCLUSIONS: Our results show protective effects
      of carotenoids on bladder cancer. They suggest that bladder cancer may be a
      preventable disease through nutritional intervention, especially in smokers.

PMID- 16890726
TI  - Preparation of a single prostate needle biopsy specimen for histological
      diagnosis and RNA analysis.
AB  - PURPOSE: When a prostate needle biopsy specimen is used for molecular study, a
      second specimen from the same area as the first one has previously been required
      for pathological diagnosis. However, we developed a method for obtaining
      substances such as RNA and we also made pathological diagnosis possible from a
      single needle biopsy specimen, improving reliability. MATERIALS AND METHODS:
      Prostate needle biopsy specimens from 118 patients were frozen in optimal cutting
      temperature compound. Tissue from the upper part of the frozen specimen was
      sectioned longitudinally for histopathological examination. The remainder of the
      specimen was placed in TRIzol reagent to extract total RNA for molecular
      biological investigation. RESULTS: Pathological diagnosis and total RNA
      extraction (1.6 to 32.7 microg) could be obtained from 1 needle biopsy specimen.
      When 2 specimens were obtained from the same area of the prostate, pathological
      diagnoses were discordant in 19% of the cases. CONCLUSIONS: We established a
      method for histopathological diagnosis in the prostate needle biopsy specimen
      used for molecular investigation. This single specimen method may facilitate
      molecular research in prostate cancer.

PMID- 16890727
TI  - Acute stress and intravesical corticotropin-releasing hormone induces mast cell
      dependent vascular endothelial growth factor release from mouse bladder explants.
AB  - PURPOSE: Corticotropin-releasing hormone is typically released from the
      hypothalamus but it has proinflammatory effects outside of the brain, possibly
      through the activation of mast cells. These cells express corticotropin-releasing
      hormone receptors with selective secretion of vascular endothelial growth factor,
      which may be involved in the pathogenesis of painful bladder
      syndrome/interstitial cystitis. This condition is characterized by bladder
      inflammation and worsened by stress. We investigated the effect of intravesical
      corticotropin-releasing hormone and acute restraint stress on vascular
      endothelial growth factor release from mouse bladder explants and the role of
      mast cells. MATERIALS AND METHODS: The bladder of C57BL/6 mast cell deficient
      (W/W(v)) and normal congenic (+/+) female mice (Jackson Laboratories, Bar Harbor,
      Maine) at ages 10 to 12 weeks was catheterized using anesthesia. After emptying
      urine 1) normal saline or corticotropin-releasing hormone was introduced for 45
      minutes, urine was collected and the mice were allowed to recover for 4 hours
      before sacrifice or 2) the mice were stressed by placing them in a restrainer for
      4 hours before sacrifice and urine was collected 2 hours after stress. The
      bladder was removed 4 hours after stress and processed for corticotropin
      releasing hormone immunohistochemical staining. In other experiments the bladder
      was removed, minced into 1 mm(2) pieces and cultured with or without
      corticotropin-releasing hormone overnight. Urine and medium were frozen for
      histamine, interleukin-6, tumor necrosis factor-alpha and vascular endothelial
      growth factor assay. RESULTS: Corticotropin-releasing hormone (100 nM) or acute
      restraint stress (4 hours) increased histamine release in urine and vascular
      endothelial growth factor release in medium without increasing interleukin-6 or
      tumor necrosis factor-alpha in the bladder explants of C57BL/6 or +/+ but not
      W/W(v) mice. No vascular endothelial growth factor, interleukin-6 or tumor
      necrosis factor-alpha was detected in urine before or after stimulation.
      Corticotropin-releasing hormone immunoreactivity was present in control bladders
      but it increased dramatically in the bladder of stressed mice. CONCLUSIONS:
      Intravesical corticotropin-releasing hormone and acute restraint stress induced
      mast cell dependent vascular endothelial growth factor release from bladder
      explants. These findings suggest that stress, corticotropin-releasing hormone,
      mast cells and vascular endothelial growth factor might participate in the
      pathogenesis of painful bladder syndrome/interstitial cystitis, which is worsened
      by stress, and provide for new therapeutic targets.

PMID- 16890728
TI  - Age related changes in the functional, biochemical and molecular properties of
      alpha1-adrenoceptors in the rat genitourinary tract.
AB  - PURPOSE: Because age related changes occur in the properties of alpha(1)
      adrenoceptor in several mammalian tissues and alpha(1)-adrenoceptor antagonists
      are extensively used to treat lower urinary tract symptoms secondary to benign
      prostatic hyperplasia, we investigated age related changes in the functional,
      biochemical and molecular properties of alpha(1)-adrenoceptor in the rat
      genitourinary tract. MATERIALS AND METHODS: The characteristics of alpha(1)
      adrenoceptor in the ventral and dorsolateral prostate, and bladder base and dome
      of 3 and 22-month-old rats were determined using an isolated muscle bath,
      radioligand receptor binding and real-time reverse transcriptase-polymerase chain
      reaction techniques. RESULTS: Old rats had significantly higher body weight,
      lower testosterone, a smaller ventral prostate and a larger bladder dome than
      young rats. Although there was no significant age dependent difference in the
      properties of alpha(1)-adrenoceptor in the bladder base and dome, total alpha(1)
      adrenoceptor density, mRNA expression of all 3 alpha(1)-adrenoceptor subtypes
      (alpha(1A), alpha(1B) and alpha(1D)) and the maximum contractile responses to
      phenylephrine were significantly lower in the ventral and dorsolateral prostate
      of 22 vs 3-month-old rats. CONCLUSIONS: Age related differences in the molecular,
      biochemical and functional properties of alpha(1)-adrenoceptors in the rat
      genitourinary tract may indicate potential differences in the response to
      alpha(1)-adrenoceptor antagonists with aging, ie a decrease in the therapeutic
      response in old vs young rats in the response to alpha(1)-adrenoceptor
      antagonists when used to treat lower urinary tract symptoms secondary to benign
      prostatic hyperplasia.

PMID- 16890729
TI  - Urodynamic effects of intravesical administration of the new small/intermediate
      conductance calcium activated potassium channel activator NS309 in freely moving,
      conscious rats.
AB  - PURPOSE: We investigated the effects of the new K+ channel activator NS309, which
      acts on small and intermediate conductance Ca2+ activated K+ channels, on
      detrusor activity in normal rats. MATERIALS AND METHODS: NS309 was given
      intravesically at different concentrations to conscious female Sprague-Dawley
      rats undergoing continuous cystometry. The effects of the drug on oxyhemoglobin
      induced detrusor overactivity were also tested. RESULTS: Intravesical NS309 (100,
      300 and 1,000 ng ml(-1)) increased bladder capacity, micturition volume and
      intercontraction intervals in a concentration dependent way. NS309 (1,000 ng ml(
      1)) given intravesically for 1 hour before instillation of intravesical
      oxyhemoglobin (250 microM) decreased or completely prevented the detrusor
      overactivity induced by oxyhemoglobin. CONCLUSIONS: Opening small and
      intermediate conductance Ca2+ activated K+ channels with NS309 given
      intravesically increased bladder capacity, micturition volume and
      intercontraction intervals in a concentration dependent way and prevented
      oxyhemoglobin induced detrusor overactivity. Results suggest that these channels
      can be interesting targets for drugs aiming to control micturition.

PMID- 16890730
TI  - Activation of the calcineurin pathway is associated with detrusor decompensation:
      a potential therapeutic target.
AB  - PURPOSE: We hypothesized that the calcineurin pathway mediated some of the
      complex remodeling process that allows a bladder subjected to partial outlet
      obstruction to adapt to its new workload. Atrial natriuretic factor mRNA
      expression served as a marker of calcineurin activation. MATERIALS AND METHODS: A
      total of 16 New Zealand White rabbits underwent surgical creation of partial
      outlet obstruction, followed by randomization to receive cyclosporin A (20 mg/kg
      intramuscularly twice daily) or no additional treatment for 14 days. Three
      animals underwent 2 weeks of partial bladder outlet obstruction followed by
      bladder biopsy and the reversal of obstruction. RESULTS: Atrial natriuretic
      factor expression was seen only in bladders with severe hypertrophy and it
      disappeared with the reversal of outlet obstruction. Cyclosporin A treatment
      resulted in a decrease in atrial natriuretic factor mRNA expression (p <0.05) and
      a marked shift in myosin heavy chain A-to-B ratios toward normal (p <0.01) and an
      increase in smooth muscle cross sectional area (p <0.05). Bladder mass decreased
      40% but did not attain statistical significance (p = 0.08). CONCLUSIONS: The
      calcineurin pathway has a significant role in bladder wall hypertrophy following
      partial outlet obstruction. Bladder hypertrophy could not be fully prevented by
      cyclosporin A, suggesting that multiple signaling pathways are involved in this
      pathophysiology. The expression of myosin heavy chain AB isoforms is regulated in
      part by the calcineurin pathway.

PMID- 16890731
TI  - In vivo hepatocyte growth factor gene transfer to bladder smooth muscle after
      bladder outlet obstruction in the rat: a morphometric analysis.
AB  - PURPOSE: We determined whether hepatocyte growth factor gene transfer after
      partial bladder outlet obstruction would prove effective for decreasing
      transforming growth factor-beta expression and consequently decreasing collagen
      deposition in partially obstructed rat bladders. MATERIALS AND METHODS: Ten-week
      old male Sprague-Dawley rats were divided into 3 groups of 10 each, including
      group 1--sham operation, group 2--bladder outlet obstruction for 4 weeks and
      group 3--hepatocyte growth factor gene transfer after bladder outlet obstruction.
      Two weeks after the onset of bladder outlet obstruction in group 3 hepatocyte
      growth factor-liposome complex (50 microg human hepatocyte growth factor cDNA)
      was injected into the smooth muscle of the rats. RESULTS: We noted no difference
      between groups 2 and 3 with regard to the ratio of bladder weight to body weight.
      The ratio in groups 2 and 3 was significantly higher than in group 1 (p = 0.043).
      The mean percent of collagen area +/- SE was 36.32% +/- 1.83%, 27.90% +/- 2.66%
      and 8.97% +/- 3.35% in groups 1 to 3, respectively (p <0.05). Relative hepatocyte
      growth factor and c-met mRNA and protein expression were higher in group 3 than
      in groups 1 and 2. However, the expression of transforming growth factor-beta1
      mRNA and protein was higher in group 2 than in groups 1 and 3. CONCLUSIONS: These
      findings may imply a possible novel therapeutic strategy against bladder
      dysfunction arising in patients with bladder outlet obstruction.

PMID- 16890732
TI  - A selective alpha1A-adrenoceptor antagonist inhibits detrusor overactivity in a
      rat model of benign prostatic hyperplasia.
AB  - PURPOSE: Alpha(1)-adrenoceptor antagonists relax the obstructed prostatic urethra
      and suppress the irritative symptoms frequently observed in patients with benign
      prostatic hyperplasia. We investigated the effects of 3 alpha(1)-adrenoceptor
      antagonists on urodynamics in rats with hormone induced benign prostatic
      hyperplasia to determine which alpha(1)-adrenoceptor subtype selective
      antagonists would suppress irritative symptoms. MATERIALS AND METHODS: Rats were
      treated with testosterone and 17beta-estradiol by weekly intramuscular
      injections. After 4 weeks a pressure flow study was done and the effects of the
      alpha(1)-adrenoceptor antagonists KMD-3213 silodosin, tamsulosin and prazosin on
      urodynamics were compared. We especially investigated the involvement of the
      bladder and prostatic urethra to clarify the mechanism of detrusor overactivity
      expression. RESULTS: Hormone treatment induced benign prostatic hyperplasia and
      resulted in detrusor overactivity, as determined by cystometry. Baseline
      perfusion urethral pressure and the phenylephrine induced increase in it were
      significantly higher in rats with vs without benign prostatic hyperplasia.
      Cystometry in hormone treated female rats did not show detrusor overactivity. KMD
      3213 decreased detrusor overactivity, similar to other alpha(1)-adrenoceptor
      antagonists. CONCLUSIONS: These results suggest that an excessive response to
      sympathetic nerve stimulation, which is mainly mediated via alpha(1A)
      adrenoceptor, in the hypertrophied prostate gives rise to detrusor overactivity.
      Furthermore, the alpha(1A)-adrenoceptor selective antagonist KMD-3213 would be
      suitable for improving irritative symptoms in patients with benign prostatic
      hyperplasia.

PMID- 16890733
TI  - Phosphodiesterase-5 isoforms: differential cyclic guanyl monophosphate binding
      and cyclic guanyl monophosphate catalytic activities, and inhibitory effects of
      sildenafil and vardenafil.
AB  - PURPOSE: We determined the differential cyclic guanyl monophosphate catalytic and
      cyclic guanyl monophosphate binding activity of phosphodiesterase-5 isoforms and
      the inhibitory effects of sildenafil (Pfizer, New York, New York) and vardenafil
      (Bayer Pharmaceutical Research, Wuppertal, Germany). MATERIALS AND METHODS:
      Coding sequences of the human phosphodiesterase-5 isoforms A1, A2 and A3 were
      cloned into pBlueBac4.5/V5-His (Invitrogen, Carlsbad, California), which allows
      the tagging of histidines at the carboxyl terminal of the expressed protein.
      Isoforms were expressed with the Bac-N-Blue baculoviral system and purified with
      the ProBond system. Expression clones were identified by polymerase chain
      reaction using vector and phosphodiesterase-5 specific primers. Purified proteins
      were verified by Western blotting. Purified proteins were analyzed for cyclic
      guanyl monophosphate catalytic and cyclic guanyl monophosphate binding activity,
      and used to determine the differential potencies of the phosphodiesterase-5
      selective inhibitors sildenafil and vardenafil. RESULTS: Cloning and expression
      of phosphodiesterase-5A1 to A3 isoforms in the baculoviral system resulted in the
      isolation of purified isoform proteins. Mean cyclic guanyl monophosphate
      catalytic activity (K(m)) +/- SD was 4.76 +/- 0.37, 4.52 +/- 0.09 and 11.39 +/-
      0.22 microM for A1 to A3, respectively. Mean cyclic guanyl monophosphate binding
      activity (K(d)) was 3.24 +/- 0.47, 1.95 +/- 0.60 and 1.70 +/- 0.47 microM for A1
      to A3, respectively. Mean IC(50) of sildenafil against phosphodiesterase-5A1 to
      A3 was 1.20 +/- 0.34, 2.83 +/- 0.56 and 2.28 +/- 0.38 nM, respectively. Mean
      IC(50) of vardenafil against phosphodiesterase-5A1 to A3 was 0.41 +/- 0.15, 0.23
      +/- 0.08 and 0.45 +/- 0.06 nM, respectively. CONCLUSIONS: Phosphodiesterase-5A1
      and A2 had similar K(m) values, while phosphodiesterase-5A3 had a much higher
      K(m) and, thus, lower cyclic guanyl monophosphate catalytic activity.
      Phosphodiesterase-5A2 and A3 had similar K(d) values, while phosphodiesterase-5A1
      had higher K(d) and, thus, lower cyclic guanyl monophosphate binding activity.
      Vardenafil was more potent (3 to 12-fold) than sildenafil for inhibiting the
      catalytic activity of all 3 human phosphodiesterase-5 isoforms with
      phosphodiesterase-5A2 showing the highest differentiation (12-fold).

PMID- 16890735
TI  - Re: Obesity, serum prostate specific antigen and prostate size: implications for
      prostate cancer detection. S. J. Freedland, E. A. Platz, J. C. Presti Jr., W. J.
      Aronson, C. L. Amling, C. J. Kane and M. K. Terris. J Urol, 175: 500-504, 2006.

PMID- 16890736
TI  - Re: Virtual cystoscopy by intravesical instillation of dilute contrast medium:
      preliminary experience. T. A. Kishore, G. K. George and S. Bhat. J Urol, 175: 870
      874, 2006.

PMID- 16890738
TI  - Re: Saturation technique does not improve cancer detection as an initial prostate
      biopsy strategy. J. S. Jones, A. Patel, L. Schoenfield, J. C. Rabets, C. D. Zippe
      and C. Magi-Galluzzi. J Urol, 175: 485-488, 2006.

PMID- 16890740
TI  - Re: Interstitial cystitis versus detrusor overactivity: a comparative,
      randomized, controlled study of cystometry using saline and 0.3 m potassium
      chloride. J. Philip, S. Willmott and P. Irwin. J Urol, 175: 566-571, 2006.

PMID- 16890742
TI  - Re: Endoscopic evidence of calculus attachment to Randall's plaque. B. R.
      Matlaga, J. C. Williams Jr., S. C. Kim, R. L. Kuo, A. P. Evan, S. B. Bledsoe, F.
      L. Coe, E. M. Worcester, L. C. Munch and J. E. Lingeman. J Urol, 175: 1720-1724,
      2006.

PMID- 16890743
TI  - Re: Is the bladder a reliable witness for predicting detrusor overactivity? H.
      Hashim and P. Abrams. J Urol, 175: 191-195, 2006.

PMID- 16890746
TI  - Re: Magnetic stimulation for mixed urinary incontinence. I. But, M. Faganelj and
      A. Sostaric. J Urol, 173: 1644-1646, 2005.

PMID- 16890748
TI  - Re: Use of nephrectomy at select medical centers--a case of follow the crowd? B.
      K. Hollenbeck, D. A. Taub, D. C. Miller, R. L. Dunn and J. T. Wei. J Urol, 175:
      670-674, 2006.

PMID- 16890750
TI  - Respiratory viral infections drive chemokine expression and exacerbate the
      asthmatic response.
AB  - A number of investigations have linked respiratory viral infections and the
      intensity and subsequent exacerbation of asthma through host response mechanisms.
      For example, it is likely that the immune-inflammatory response to respiratory
      syncytial virus can cause a predisposition toward an intense inflammatory
      reaction associated with asthma, and adenovirus might cause exacerbation of the
      immune response associated with chronic obstructive pulmonary disease. In each of
      these situations, the host's immune response plays a critical mechanistic role
      through the production of certain cytokines and chemokines. Specific aspects of
      these augmented immune responses are determined by the biology of the virus, the
      genetic variability of the host, and the cytokine-chemokine phenotype of the
      involved tissue. For instance, the type 1/type 2 cytokine ratio in the airways
      during infection with rhinovirus determines how long the viral infection endures.
      By this same theory, it has been demonstrated that chemokine levels produced
      during respiratory syncytial virus infection determine host responses to later
      immune stimuli in the lung, with the potential to augment the asthmatic response.
      Further research in this area will clarify cytokines, chemokines, or cell
      targets, which will provide the basis for next-generation therapies.

PMID- 16890751
TI  - Chemokines and their receptors in allergic disease.
AB  - Mechanisms of chemoattraction underlie the spatial organization of the cells of
      the immune system under basal conditions and the localization of these cells to
      sites of inflammation. The chemokines, a family of around 50 small proteins, play
      a major role in these processes. Leukocytes are equipped with cell-surface
      sensors for chemokines. There are 19 such receptors that are differentially
      expressed on leukocytes: the repertoire of receptor expression depending on the
      type of leukocyte and its stage in maturation. From observations in animal
      models, clinical studies, in vitro cell biology, and molecular analysis, a
      working hypothesis has been established to explain the cellular interactions
      underlying allergic responses and the chemokines-chemokine receptors involved.
      Chemokines signal through G protein-coupled receptors that are used typically for
      sensory functions (eg, detection of olfactory signals in the nose). This type of
      receptor can be blocked selectively by small-molecule antagonists. This provides
      the opportunity for the development of therapeutic compounds designed to suppress
      the recruitment of particular leukocyte types in allergic reactions.

PMID- 16890754
TI  - Recent progress in the biology of airway dendritic cells and implications for
      understanding the regulation of asthmatic inflammation.
AB  - Dendritic cells (DCs) are crucial in determining the outcome of antigen encounter
      and integrating signals derived from the antigen, its inflammatory context, and
      the host environment into a signal that can be read by naive T cells in the
      lymphoid tissues and by effector T cells in peripheral tissues. Airway DC
      subsets, however, induce different types of immune responses, with plasmacytoid
      DCs promoting tolerance and myeloid DCs inducing immunity. We also propose that
      airway DCs are not only crucial for sensitization to inhaled antigens, leading to
      allergy, but also play a crucial role in established inflammation and therefore
      represent a therapeutic target to prevent the development of airway diseases.

PMID- 16890753
TI  - Absence of detectable viremia in a perinatally HIV-1-infected teenager after
      discontinuation of antiretroviral therapy.
AB  - A 15-year-old girl with perinatal HIV-1 infection has remained asymptomatic with
      undetectable plasma HIV-1 viremia for more than 5 years after discontinuing all
      antiretroviral therapy. Viral sequence analysis of proviral HIV-1 DNA revealed no
      evident fitness-attenuating deletions or mutations. This subject exhibited an
      unusually robust HIV-specific T-cell response, with an intact CD4+ T cell
      proliferative response to HIV-1 antigens. In addition, the subject was found to
      be heterozygous for the 32-bp deletion in the CCR5 gene, which encodes the
      primary coreceptor for HIV-1 entry into cells. This mutation mediates profound
      resistance to HIV infection in homozygotes and has been associated with delayed
      disease progression in heterozygotes after both horizontal and vertical HIV-1
      infection. Although adults with long-term nonprogressive HIV disease have been
      studied at length, there is no prior description in the literature of a
      perinatally HIV-infected child whose plasma HIV-1 viremia is controlled to
      undetectable levels in the absence of antiretroviral therapy.

PMID- 16890755
TI  - Small airway disease: a riddle wrapped in a mystery inside an enigma.

PMID- 16890756
TI  - The functional benefit of anti-inflammatory aerosols in the lung periphery.
AB  - BACKGROUND: The target of anti-inflammatory therapy in asthma is thought to be
      situated, at least partly, in the lung periphery, and inhaled steroid aerosols
      are being engineered to reach it. However, the potential effect of such aerosols
      cannot be fully evaluated by conventional lung function tests because these are
      insensitive to peripheral lung structure. OBJECTIVE: A prospective cohort study
      was conducted to investigate whether ultrafine steroid aerosols can elicit a
      response in the lung periphery, using a validated multibreath washout technique
      that can distinguish acinar from conductive lung zone function. METHODS: In 30
      stable patients with asthma with a wide range of disease severity (FEV(1) 27% to
      108% predicted), we assessed conductive and acinar airway function abnormality at
      baseline, with patients on a standard dry powder steroid aerosol and after
      switching them to an ultrafine steroid aerosol. RESULTS: Only in those patients
      with abnormal acinar airway function at baseline (n = 16) did acinar
      heterogeneity show a consistent improvement after switching to an ultrafine
      steroid aerosol; the improvement was also correlated with baseline acinar
      heterogeneity (r = -0.67; P = .007). Although all patients with asthma also
      presented conductive airway abnormality at baseline, no changes were observed in
      this lung zone with the switch to the ultrafine aerosol (P > .1). CONCLUSION:
      Among stable patients with asthma, those with acinar lung zone abnormality at
      baseline have the potential to receive functional benefit from an ultrafine
      steroid aerosol. Clinical studies comparing the efficacy of steroid aerosols
      targeted to the deep lung should at least include a measurement of peripheral
      lung zone function. CLINICAL IMPLICATIONS: A new noninvasive measure of small
      airways function reveals why, and for which particular patients with asthma,
      small steroid aerosol particles can be of therapeutic use.

PMID- 16890757
TI  - Effects of a leukotriene receptor antagonist on exhaled leukotriene E4 and
      prostanoids in children with asthma.
AB  - BACKGROUND: Leukotriene (LT) E(4) and 8-isoprostane concentrations are elevated
      in exhaled breath condensate in children with asthma. The effects of leukotriene
      receptor antagonists (LTRAs) on exhaled leukotriene and prostanoids in children
      with asthma are unknown. OBJECTIVE: (1) To study the effect of montelukast, a
      LTRA, on exhaled LTE(4), 8-isoprostane, and prostaglandin E(2) in children with
      asthma and atopic children; (2) to measure exhaled nitric oxide. METHODS: An open
      label study with oral montelukast (5 mg once daily for 4 weeks) was undertaken in
      17 atopic children with asthma and 16 atopic children without asthma. RESULTS:
      Pretreatment exhaled LTE(4) (P < .0001) and 8-isoprostane (P < .0001) values were
      higher in atopic children with asthma than in atopic children without asthma. In
      atopic children with asthma, montelukast reduced exhaled LTE(4) by 33% (P <
      .001), and this reduction was correlated with pretreatment LTE(4) values (r = 
      0.90; P = .0001). Posttreatment exhaled LTE(4) levels in children with asthma
      were higher than pretreatment LTE(4) values in atopic children without asthma (P
      < .004). Montelukast had no effect on exhaled LTE(4) in atopic children without
      asthma (P = .74), or on exhaled 8-isoprostane (atopic children with asthma, P =
      .94; atopic children without asthma, P = .55) and PGE(2) (atopic children with
      asthma, P = .56; atopic children without asthma, P = .93) in both groups. In
      atopic children with asthma, exhaled nitric oxide concentrations were reduced by
      27% (P < .05) after montelukast. CONCLUSION: Leukotriene receptor antagonists
      decrease exhaled LTE(4) in atopic children with asthma. This reduction is
      dependent on baseline exhaled LTE(4) values. CLINICAL IMPLICATIONS: Measurement
      of exhaled LTE(4) might help identify children with asthma most likely to benefit
      from LTRAs.

PMID- 16890758
TI  - Diesel exhaust exposure favors TH2 cell recruitment in nonatopic subjects by
      differentially regulating chemokine production.
AB  - BACKGROUND: The prevalence of allergic diseases has increased in the last 20
      years, and a number of studies have shown that diesel exhaust particle-associated
      polyaromatic hydrocarbons can exacerbate the allergic reaction. Much less is
      known about their potential capacity to generate a T(H)2-type allergic reaction
      in nonatopic subjects. OBJECTIVE: The aim of this study was to test the
      hypothesis that diesel exhaust exposure might favor, in nonatopic donors, T(H)2
      type cell recruitment, either through increased production of T(H)2-attracting
      chemokines or decreased production of T(H)1-attracting chemokines. METHODS: PBMCs
      from nonatopic donors were incubated with diesel exhaust particle-polyaromatic
      hydrocarbons, and the supernatants were evaluated for the presence of pro-T(H)1
      chemokines (IFN-gamma-induced protein 10 and monokine Induced by IFN-gamma) and
      pro-T(H)2 chemokines (macrophage-derived chemokine, I-309, and pulmonary and
      activation-regulated chemokine) by means of ELISA. The functional effect was
      evaluated by using chemotaxis assays with polarized T(H)1 and T(H)2 cells.
      RESULTS: Diesel exhaust exposure of PBMCs from nonatopic donors induced a late
      increase after 48 hours in pulmonary and activation-regulated chemokine mediated
      by IL-13 and a decrease in IFN-gamma-induced protein 10 levels selectively at
      both the protein and mRNA levels. The functional effect of these chemokine
      variations resulted in an enhanced chemotaxis of T(H)2, but not T(H)1, cells.
      CONCLUSION: These findings show that diesel exhaust exposure might be involved in
      the genesis of allergic diseases by differentially regulating chemokines favoring
      the recruitment of T(H)2 cells in nonatopic subjects. CLINICAL IMPLICATIONS:
      Environmental factors, especially air pollution, might favor the genesis of
      allergic diseases.

PMID- 16890759
TI  - IgE and IgG anti-house dust mite specificities in allergic disease.
AB  - BACKGROUND: There are few studies that quantitatively compare IgE and IgG
      antibody binding to the major and minor house dust mite allergens. OBJECTIVE: To
      measure the IgE and IgG antibody specificities produced by adults and children,
      including children admitted to an emergency department for asthma. METHODS:
      Antibodies were measured by solid-phase microtiter assays. RESULTS: Children
      recruited from the emergency department had similar titers and patterns of IgE
      antibody binding compared with children without acute disease. Der p 1 and 2
      bound 50% to 65% of the IgE antibody, and most of the remaining binding was to
      Der p 4, 5, and 7. Der p 3, 8, 10, and 20 induced low titers. The pattern was
      similar across a wide range of antihouse dust mite titers. IgG(1) and IgG(4)
      antibodies predominantly bound the major and midrange allergens and were mainly
      found in children with allergy. Children recruited in the emergency department
      had lower titers. CONCLUSION: The same IgE antibody-binding pattern and
      predominant contribution of Der p 1 and 2 was found across a wide range of total
      IgE antibody titers and for children admitted to an emergency department. IgG(1)
      and IgG(4) antibodies bound to the more allergenic specificities and were largely
      found in children with allergy. The IgG antibody titers were lower in sera from
      children admitted to the emergency department for asthma exacerbations. CLINICAL
      IMPLICATIONS: Der p 1 and 2 and possibly Der p 4, 5, and 7 provide a formulation
      suitable for immunotherapy and diagnosis. Low IgG antibodies were a feature of
      acute disease.

PMID- 16890760
TI  - Systemic glucocorticoid reduces bronchial mucosal activation of activator protein
      1 components in glucocorticoid-sensitive but not glucocorticoid-resistant
      asthmatic patients.
AB  - BACKGROUND: Overexpression of the transcriptional regulatory factor activator
      protein 1 might contribute to T-cell glucocorticoid (GC) refractoriness in GC
      resistant asthma. OBJECTIVE: We sought to address the hypothesis that clinically
      GC-resistant asthma is accompanied by failure of systemic GCs to inhibit
      phosphorylation of c-jun and c-jun N-terminal kinase (JNK) in bronchial mucosal
      cells. METHODS: We performed enumeration of total (CD45+) leukocytes and cells
      expressing c-fos and total and phosphorylated c-jun and JNK in bronchial biopsy
      sections from 9 GC-sensitive and 17 GC-resistant asthmatic patients taken before
      and after oral prednisolone (40 mg/1.72 m(2) body surface area daily for 14 days)
      using specific antibodies, immunohistochemistry, and image analysis. RESULTS: At
      baseline, mean total (CD45+) mucosal leukocytes, total cells expressing
      phosphorylated c-jun and JNK, and mean percentages of cells in which these
      molecules were phosphorylated were similar in both groups, whereas mean total
      numbers of c-fos-immunoreactive cells were increased in the GC-resistant
      asthmatic subjects (P = .04). After prednisolone, the mean total cells expressing
      phosphorylated c-jun and JNK and the mean percentages of cells in which these
      molecules were phosphorylated were significantly reduced in the GC-sensitive (P <
      or = .02) but not the GC-resistant asthmatic subjects. Mean total CD45+
      leukocytes and c-fos-immunoreactive cells were not significantly altered in
      either group. CONCLUSION: Clinical GC responsiveness in asthma is accompanied by
      reduced phosphorylation of bronchial mucosal c-jun and JNK, a phenomenon not seen
      in resistant patients. CLINICAL IMPLICATIONS: Dysregulation of activator protein
      1 activation leading to clinical GC resistance might reflect identifiable
      environmental influences and is a target for future therapy.

PMID- 16890761
TI  - Identification of alpha-enolase as an autoantigen associated with severe asthma.
AB  - BACKGROUND: Approximately 5% to 10% of patients with asthma have severe disease
      that is not effectively controlled by typical therapies. The existence of an
      autoantigen associated with severe asthma has been previously reported.
      OBJECTIVE: We attempted to identify the autoantigen. METHODS: Severe asthma was
      defined as patients having at least 1 severe asthmatic exacerbation requiring an
      emergency department visit or admission in the last year despite continuous
      typical therapies. Autoantibodies to airway epithelial cells (A549) were examined
      in sera from patients with severe asthma by immunoblot analysis. RESULTS: IgG
      autoantibodies to the 52-kd airway epithelial cell antigen were detected in sera
      from 32 of 78 patients with severe asthma (41%), 9 of 83 patients with mild-to
      moderate asthma (11%), and 2 of 58 healthy controls (3%; P < .001). The 52-kd
      autoantigen was identified as alpha-enolase by mass spectrometry analysis and
      confirmed by using recombinant human alpha-enolase protein. The detection of IgG
      autoantibodies to alpha-enolase was the most significant indicator for
      distinguishing severe asthma from mild-to-moderate asthma, even after adjusting
      for the effects of other clinical variables, including age, sex, atopy, and
      FEV(1) (adjusted odds ratio, 5.2; 95% CI, 2.1-12.9; P < .001). CONCLUSION: The
      alpha-enolase was identified as an autoantigen associated with severe asthma.
      Further studies are needed to determine the significance of this autoantigen in
      severe asthma. CLINICAL IMPLICATIONS: IgG autoantibodies to alpha-enolase could
      be a biological marker for severe asthma.

PMID- 16890762
TI  - Heaves, an asthma-like equine disease, involves airway smooth muscle remodeling.
AB  - BACKGROUND: Increased airway smooth muscle mass is a prominent feature of
      asthmatic airway remodeling. Airway smooth muscle hyperplasia occurs in rodent
      models of experimental asthma, but the relevance of such finding to spontaneously
      occurring disease in large mammals is unknown. OBJECTIVE: We examined horses with
      heaves, a naturally occurring equine asthma related to sensitization and exposure
      to moldy hay. We hypothesized that airway remodeling occurs in heaves and shares
      disease mechanisms with asthma. METHODS: We quantified the airway smooth muscle
      mass and the numbers of proliferating and apoptotic airway smooth muscle cells in
      5 horses with heaves and 5 control horses using morphometric techniques. Cell
      proliferation was detected in tissue sections by immunostaining for proliferating
      cell nuclear antigen, and apoptotic cells were detected by terminal
      deoxynucleotidyl transferase-mediated dUTP nick end labeling of fragmented DNA.
      Both signals were colocalized with smooth muscle specific alpha-actin. RESULTS:
      Horses with heaves had a significant increase in the amount of smooth muscle in
      the airways (nearly triple that of the controls) associated with increased
      myocyte proliferation (7-fold proliferating cell nuclear antigen-positive airway
      myocytes) and apoptosis (6-fold). CONCLUSION: Heaves involves airway smooth
      muscle growth associated with myocyte hyperplasia, which may contribute to the
      growth, and increased myocyte apoptosis that may reflect a compensatory mechanism
      serving to limit the abnormal smooth muscle growth. CLINICAL IMPLICATIONS: Airway
      smooth muscle remodeling in heaves may be involved in the mechanism of airway
      hyperresponsiveness and chronic lung function impairment in a way comparable to
      human asthma.

PMID- 16890763
TI  - Adiponectin attenuates allergen-induced airway inflammation and
      hyperresponsiveness in mice.
AB  - BACKGROUND: Epidemiologic data indicate an increased incidence of asthma in the
      obese. OBJECTIVE: Because serum levels of the insulin-sensitizing and anti
      inflammatory adipokine adiponectin are reduced in obese individuals, we sought to
      determine whether exogenous adiponectin can attenuate allergic airway responses.
      METHODS: We sensitized and challenged BALB/cJ mice with ovalbumin (OVA). Alzet
      micro-osmotic pumps were implanted in the mice to deliver continuous infusions of
      buffer or adiponectin (1.0 microg/g/d), which resulted in an approximate 60%
      increase in serum adiponectin levels. Two days later, mice were challenged with
      aerosolized saline or OVA once per day for 3 days. Mice were examined 24 hours
      after the last challenge. RESULTS: OVA challenge increased airway responsiveness
      to intravenous methacholine, bronchoalveolar lavage fluid cells, and T(H)2
      cytokine levels. Importantly, each of these responses to OVA was reduced in
      adiponectin- versus buffer-treated mice. OVA challenge caused a 30% reduction in
      serum adiponectin levels and a corresponding decrease in adipose tissue
      adiponectin mRNA expression. OVA challenge also decreased pulmonary mRNA
      expression of each of 3 proposed adiponectin-binding proteins, adiponectin
      receptor 1, adiponectin receptor 2, and T-cadherin. CONCLUSION: Our results
      indicate that serum adiponectin is reduced during pulmonary allergic reactions
      and that adiponectin attenuates allergic airway inflammation and airway
      hyperresponsiveness in mice. CLINICAL IMPLICATIONS: The data suggest that
      adiponectin might play a role in the relationship between obesity and asthma.

PMID- 16890764
TI  - Fine mapping and positional candidate studies on chromosome 5p13 identify
      multiple asthma susceptibility loci.
AB  - BACKGROUND: Genome-wide linkage scans to identify asthma susceptibility loci have
      revealed many linked regions, including a broad region on chromosome 5p.
      OBJECTIVE: To identify a 5p-linked asthma or bronchial hyperresponsiveness (BHR)
      locus. METHODS: We performed fine mapping and positional candidate studies of
      this region in the Hutterites and an outbred case-control sample from Germany by
      genotyping 89 single nucleotide polymorphisms (SNPs) in 22 genes. SNP and
      haplotype analyses were performed. RESULTS: Three genes in a distal region (zinc
      finger RNA binding protein [ZFR], natriuretic peptide receptor C, and a
      disintegrin and metalloproteinase domain with thrombospondin type 1 motif
      [ADAMTS12]) were associated with BHR, whereas 4 genes in a proximal region
      (prolactin receptor, IL-7 receptor [IL7R], leukemia inhibitory factor receptor
      [LIFR], and prostaglandin E4 receptor [PTGER4]) were associated with asthma
      symptoms in the Hutterites. Furthermore, nearly the entire original linkage
      signal in the Hutterites was generated by individuals who had the risk-associated
      alleles in ZFR3, natriuretic peptide receptor C, ADAMTS12, LIFR, and PTGER4.
      Variation in ADAMTS12, IL7R, and PTGER4 were also associated with asthma in the
      outbred Germans, and the frequencies of long-range haplotypes composed of SNPs at
      ZFR, ADAMTS12, IL7R, LIFR, and PTGER4 were significantly different between both
      the German and Hutterite cases and controls. There is little linkage
      disequilbrium between alleles in these 2 regions in either population.
      CONCLUSION: These results suggest that a broad region on 5p, separated by >9 Mb,
      harbors at least 2 and possibly 5 asthma or BHR susceptibility loci. These
      findings are consistent with the hypothesis that regions providing evidence for
      linkage in multiple populations may, in fact, house more than 1 susceptibility
      locus, as appears to be the case for the linked region on 5p. CLINICAL
      IMPLICATIONS: Identifying asthma or BHR genes could lead to novel therapeutic
      approaches.

PMID- 16890765
TI  - Phosphoinositide 3-kinase-delta inhibitor reduces vascular permeability in a
      murine model of asthma.
AB  - BACKGROUND: Bronchial asthma is characterized by inflammation of the airways,
      which is usually accompanied by increased vascular permeability, resulting in
      plasma exudation. Vascular endothelial growth factor (VEGF) has been implicated
      in contributing to asthmatic tissue edema through its effect on vascular
      permeability. Many cellular responses of VEGF are regulated by the lipid products
      of phosphoinositide 3-kinase (PI3K). However, the effect of PI3K catalytic
      subunit p110delta on VEGF-mediated signaling is unknown. Recently, an isoform
      specific small molecule inhibitor, IC87114, which is selective for p110delta
      catalytic activity, has been identified. OBJECTIVE: We have sought to investigate
      the role of PI3K-delta, more specifically in the increase of vascular
      permeability. METHODS: Female BALB/c mice were sensitized and challenged with
      ovalbumin. We have investigated the effect of IC87114 on airway inflammation,
      T(H)2 cytokines expression, airway hyperresponsiveness, plasma extravasation,
      hypoxia-inducible factor 1alpha expression, and VEGF expression in a murine model
      of asthma. RESULTS: Our current study has revealed that IC87114 reduces antigen
      induced airway infiltration of inflammatory cells, secretion of T(H)2 cytokines
      in lungs, airway hyperresponsiveness, and vascular permeability. Moreover, we
      have found that inhibition of p110delta reduces ovalbumin-induced upregulation of
      VEGF level. CONCLUSION: These results suggest that PI3K-delta inhibitor
      attenuates antigen-induced airway inflammation and hyperresponsiveness by
      preventing vascular leakage in mice. CLINICAL IMPLICATIONS: These findings
      provide a crucial molecular mechanism for the potential role of PI3K-delta in
      asthma and other airway inflammatory disorders.

PMID- 16890766
TI  - IL-4 induces IL-13-independent allergic airway inflammation.
AB  - BACKGROUND: The related T(H)2 cytokines IL-4 and IL-13 are produced during
      allergic responses, signal through receptors that contain IL-4 receptor (IL-4R)
      alpha, and promote allergic inflammation by activating signal transducer and
      activator of transcription 6. IL-4 promotes T(H)2 response induction, and IL-13
      is necessary and sufficient to induce airways hyperresponsiveness (AHR) and
      goblet cell hyperplasia in some mouse models of asthma. The nonredundant role of
      IL-13 could reflect unique IL-13 activation of a signaling pathway, inhibitory
      effects induced by IL-4 but not IL-13, or greater production-potency of IL-13
      than IL-4. OBJECTIVES: We sought to distinguish among these possibilities by
      determining whether IL-4 inhalation can induce acute allergic airways disease in
      the absence of IL-13. METHODS: Mice were inoculated intratracheally with IL-13 or
      a long-acting formulation of IL-4. Responses of IL-13-deficient and IL-13
      sufficient mice were compared, as were responses in mice treated with a potent IL
      13 antagonist, anti-IL-4Ralpha antibody, or control reagents. RESULTS: IL-4
      inhalation stimulated bronchoalveolar lavage fluid eosinophilia, AHR, and goblet
      cell hyperplasia. These responses were similar in IL-13-deficient and IL-13
      sufficient mice and were not inhibited by an IL-13 antagonist but were blocked by
      anti-IL-4Ralpha antibody. CONCLUSION: IL-4 can induce IL-13-independent AHR and
      goblet cell hyperplasia. Thus the greater role for IL-13 than IL-4 in the
      induction of these acute allergy-related changes reflects increased production,
      potency, or both of IL-13 relative to IL-4 rather than a unique IL-13-signaling
      pathway or a suppressive effect of IL-4. CLINICAL IMPLICATIONS: Dual IL-4/IL-13
      inhibition might be more effective than selective IL-13 inhibition at suppressing
      allergic inflammation in some circumstances.

PMID- 16890767
TI  - Experimental gastrointestinal allergy enhances pulmonary responses to specific
      and unrelated allergens.
AB  - BACKGROUND: Gastrointestinal allergy often precedes or coexists with respiratory
      allergy. OBJECTIVE: We hypothesized that established experimental
      gastrointestinal allergy would prime for the development of allergic respiratory
      responses. METHODS: BALB/c mice were sensitized with ovalbumin (OVA) in the
      presence of aluminum potassium sulfate and then subjected to intragastric saline
      or OVA challenges. After the development of allergen-induced gastrointestinal
      allergy, mice were intranasally exposed to either saline, OVA, or a
      neoaeroallergen house dust mite (HDM) extract. Airway inflammation (eg,
      bronchoalveolar lavage fluid cellularity, cytokine levels, and OVA-specific
      antibody levels) and airway responsiveness to methacholine exposure were assessed
      after intranasal allergen exposure. RESULTS: A single intranasal exposure to OVA
      induced significantly more airway inflammation in intragastric OVA-challenged
      mice compared with that seen in intragastric saline-treated mice. Kinetic
      analysis revealed that the observed amplification of lung inflammation was
      sustained for up to 12 days after the last intragastric OVA challenge after
      resolution of blood eosinophilia. When mice with gastrointestinal allergy were
      repeatedly challenged with HDM in the respiratory tract, they experienced
      enhanced airway inflammation, including bronchoalveolar lavage fluid eosinophilia
      and increased IL-13 levels. CONCLUSION: Taken together, our results demonstrate
      that OVA-induced gastrointestinal allergy enhances not only allergic airway
      responses to OVA but also to HDM, an unrelated aeroallergen. CLINICAL
      IMPLICATIONS: Experimental gastrointestinal allergy primes for responses to
      allergens in the respiratory tract, enhancing antigen-specific antibody and T(H)2
      cytokine production, airway inflammation, and airway hyperresponsiveness.

PMID- 16890768
TI  - Localization of nerve growth factor and its receptors in the human nasal mucosa.
AB  - BACKGROUND: Nerve growth factor (NGF) is a pluripotent mediator, the levels of
      which are elevated in nasal lavage fluids of individuals with allergic rhinitis
      at baseline. Levels of NGF increase after allergen challenge. OBJECTIVE: In the
      current study, we tested the hypotheses that mast cells are the main source of
      human nasal NGF, and that NGF can potentially affect mucosal elements other than
      nerves. METHODS: Immunostaining with antibodies against NGF, tryptase, CD3,
      eosinophil cationic protein, and the high-affinity (tyrosine kinase A) and low
      affinity (p75) receptors for NGF was performed by using human nasal turbinate
      sections. RESULTS: Double immunofluorescence staining demonstrated NGF in only 2%
      (median) (1.3, 2.3; 25th, 75th percentiles) of mast cells, 0.2% (0, 0.4) of T
      cells, but in 62.2% (56.5, 68) of activated eosinophils. With immunohistology,
      NGF expression was consistently strongest in the submucosal glands and lesser in
      the epithelial lining. Both high-affinity and low-affinity receptors for NGF were
      localized not only on nerves, as expected, but also on nasal epithelium,
      submucosal glands, and some interstitial cells, but not on vascular endothelium.
      CONCLUSION: This study demonstrates that submucosal glands, nasal epithelium, and
      eosinophils constitute the major sources of NGF in the human nasal mucosa. That
      NGF receptors are found in cells other than nerves supports the notion that the
      role of this neurotrophin is broader than simple modulation of the sensorineural
      system. CLINICAL IMPLICATIONS: The distribution of NGF and its receptors and its
      established release during allergic reactions suggest that this factor
      participates in the pathophysiology of allergic rhinitis.

PMID- 16890769
TI  - Efficacy and safety of sublingual immunotherapy with grass allergen tablets for
      seasonal allergic rhinoconjunctivitis.
AB  - BACKGROUND: Allergen immunotherapy (desensitization) by injection is effective
      for seasonal allergic rhinitis and has been shown to induce long-term disease
      remission. The sublingual route also has potential, although definitive evidence
      from large randomized controlled trials has been lacking. OBJECTIVE: The aim was
      to confirm the efficacy of a rapidly dissolving grass allergen tablet (GRAZAX,
      ALK-Abello, Horsholm, Denmark) compared with placebo in patients with seasonal
      rhinoconjunctivitis. METHODS: A longitudinal, double-blind, placebo-controlled,
      parallel-group study that included 51 centers from 8 countries. Subjects were
      randomized (1:1) to receive a grass allergen tablet or placebo once daily. A
      total of 634 subjects with a history of grass pollen-induced rhinoconjunctivitis
      for at least 2 years and confirmation of IgE sensitivity (positive skin prick
      test and serum-specific IgE) were included in the study. Subjects commenced
      treatment at least 16 weeks before the grass pollen season, and treatment was
      continued throughout the entire season. RESULTS: The primary efficacy analysis
      showed a reduction of 30% in rhinoconjunctivitis symptom score (P < .0001) and a
      reduction of 38% in rhinoconjunctivitis medication score (P < .0001) compared
      with placebo. Side effects mainly comprised mild itching and swelling in the
      mouth that was in general well tolerated and led to treatment withdrawal in less
      than 4% of participants. There were no serious local side effects and no severe
      systemic adverse events. CONCLUSION: Sublingual immunotherapy with grass allergen
      tablets was effective in grass pollen-induced rhinoconjunctivitis. The tablet was
      well tolerated with minor local side effects. CLINICAL IMPLICATIONS: The grass
      allergen tablet represents a safe alternative to injection immunotherapy suitable
      for home use.

PMID- 16890770
TI  - Challenge with environmental tobacco smoke exacerbates allergic airway disease in
      human beings.
AB  - BACKGROUND: Despite widespread perceptions that environmental tobacco smoke (ETS)
      is a potent risk factor for allergic airway disease, epidemiologic studies
      studying this have been equivocal. There is a clear need for experimental studies
      to address these questions. OBJECTIVE: We directly tested the hypothesis that ETS
      could interact with allergen in human beings to alter immune responses and
      promote changes associated with allergic airway disease. METHODS: In a
      randomized, placebo-controlled crossover study, 19 nonsmoking volunteers with
      ragweed allergy underwent nasal lavage followed by controlled chamber exposures
      to 2 hours ETS or clean air followed by another nasal lavage. Subjects
      immediately randomly received nasal challenge with either ragweed allergen or
      placebo (300 microL saline). Lavages were also performed 10 minutes, 24 hours,
      and 4 and 7 days after challenge and IgE, cytokines, and histamine measured. The
      other arms of the study were spaced at least 6 weeks apart. RESULTS:
      Environmental tobacco smoke promoted the production of allergen-specific IgE, the
      hallmark of allergic disease in nasal lavage fluid. Four days after exposure to
      ETS/ragweed, levels were on average 16.6-fold higher than after clean air/ragweed
      challenge. In addition, ETS (vs air) promoted the induction of a T(H)2-cytokine
      nasal milieu (increased IL-4, IL-5, and IL-13 and decreased IFN-gamma
      production), characteristic of an active allergic response. Moreover, nasal
      histamine levels were 3.3-fold greater after ETS/ragweed challenge than after
      clean air/ragweed challenge. CONCLUSION: These studies provide the first
      experimental evidence that secondhand smoke can exacerbate allergic responses in
      human beings. CLINICAL IMPLICATIONS: The studies suggest that patients with
      allergies should avoid tobacco smoke.

PMID- 16890771
TI  - Natural rubber latex allergy among health care workers: a systematic review of
      the evidence.
AB  - BACKGROUND: Natural rubber latex is a recognized allergen, but a recent meta
      analysis failed to find any association between latex exposure and allergy in
      health care workers (HCWs). OBJECTIVES: A meta-analysis was carried out under the
      auspices of the French National Regulatory Authority to assess the allergic risk
      induced by latex gloves in HCWs. METHODS: The risk of work-related exposure to
      latex for the development of latex allergy was assessed. Prevalence and incidence
      rates of latex sensitization or allergy were compared in HCWs and in the general
      population. Exposure-response relationships were assessed in HCWs. RESULTS: Latex
      allergy was found in 4.32% (range, 4.01% to 4.63%) of HCWs and in 1.37% (range,
      0.43% to 2.31%) of the general population. Latex-positive skin prick test
      responses ranged from 2.1% to 3.7% in the general population and from 6.9% to
      7.8% for the HCWs. HCWs exposed to latex showed an increased risk of hand
      dermatitis (odds ratio [OR], 2.46; 95% CI, 2.11-2.86), asthma or wheezing (OR,
      1.55; 95% CI, 1.15-2.08), rhinoconjunctivitis (OR, 2.73; 95% CI, 1.97-3.81), and
      at least one generic symptom (OR, 1.27; 95% CI, 1.09-1.47). Sensitization to
      latex was significantly associated with asthma and rhinoconjunctivitis. By
      contrast, exposure to latex was not associated with a significantly increased
      risk of positive skin prick test responses to latex (OR, 1.47; 95% CI, 0.94
      2.30). CONCLUSION: HCWs have an increased risk of sensitization and allergic
      symptoms to latex. CLINICAL IMPLICATIONS: Prevention of latex allergy in HCWs is
      needed.

PMID- 16890772
TI  - Pro-oxidative diesel exhaust particle chemicals inhibit LPS-induced dendritic
      cell responses involved in T-helper differentiation.
AB  - BACKGROUND: Epidemiologic studies show that exposure to ambient particulate
      matter leads to asthma exacerbation. Diesel exhaust particles (DEPs), a model
      pollutant, act as an adjuvant for allergic sensitization. Increasing evidence
      shows that this effect could be mediated by an effect on dendritic cells (DCs).
      OBJECTIVE: Our aim was to elucidate the mechanism by which pro-oxidative DEP
      chemicals change DC function so that these antigen-presenting cells strengthen
      the immune response to an experimental allergen. METHODS: We exposed murine bone
      marrow-derived DCs and a homogeneous myeloid DC line, BC1, to DEPs and organic
      extracts made from these particles to determine how the induction of oxidative
      stress affects cellular maturation, cytokine production, and activation of
      antigen-specific T cells. RESULTS: DEP extracts induced oxidative stress in DCs.
      This change in redox equilibrium interfered in the ability of Toll-like receptor
      agonists to induce the expression of maturation receptors (eg, CD86, CD54, and I
      A(d)) and IL-12 production. This perturbation of DC function was accompanied by
      decreased IFN-gamma and increased IL-10 induction in antigen-specific T cells.
      The molecular basis for the perturbation of DC function is the activation of a
      nuclear factor-erythroid 2 (NF-E2)-related factor 2-mediated signaling pathway
      that suppresses IL-12 production. NF-E2-related factor 2 deficiency abrogates the
      perturbation of DC function by DEPs. CONCLUSION: These data provide the first
      report that pro-oxidative DEP chemicals can interfere in T(H)1-promoting response
      pathways in a homogeneous DC population and provide a novel explanation for the
      adjuvant effect of DEPs on allergic inflammation. CLINICAL IMPLICATIONS: These
      data clarify the adjuvant effect of particulate air pollutants in allergic
      inflammatory disease.

PMID- 16890773
TI  - Accidental ingestions in children with peanut allergy.
AB  - BACKGROUND: Accidental exposure to peanut has been reported to occur frequently.
      Total avoidance of peanut is difficult because of its widespread use,
      manufacturing and labeling errors, utensil contamination, and label
      misinterpretation. OBJECTIVE: Given the apparent increased awareness of peanut
      allergy by both consumers and food manufacturers, we aimed to determine the
      current frequency of accidental exposures occurring in peanut allergic children
      in Quebec and to identify factors associated with exposure. METHODS: The parents
      of children with peanut allergy diagnosed at the Montreal Children's Hospital
      completed questionnaires about accidental exposure to peanut occurring over the
      period of the preceding year. Logistic regression was used to identify associated
      factors. RESULTS: Of 252 children, 62% were boys, with a mean age of 8.1 years
      (SD, 2.9). The mean age at diagnosis was 2.0 years (SD, 2.1). Thirty-five
      accidental exposures occurred in 29 children over a period of 244 patient-years,
      yielding an annual incidence rate of 14.3% (95% CI, 10.0% to 19.9%). Fifteen
      reactions were mild, 16 moderate, and 4 severe. Of 20 reactions that were
      moderate to severe, only 4 received epinephrine. Eighty percent of children
      attended schools prohibiting peanut, and only 1 accidental exposure occurred at
      school. No associated factors were identified. CONCLUSION: Accidental exposure to
      peanut occurs at a lower frequency than previously reported, but most reactions
      are managed inappropriately. CLINICAL IMPLICATIONS: Enhanced awareness, access to
      safer environments, and good food manufacturing practices may have contributed to
      a lower incidence of inadvertent peanut exposure, but a further reduction and
      better education on allergy management are desirable.

PMID- 16890774
TI  - Effect of in vitro gastric and duodenal digestion on the allergenicity of grape
      lipid transfer protein.
AB  - BACKGROUND: Severe grape allergy has been linked to lipid transfer protein (LTP)
      sensitization. LTPs are known to be resistant to pepsin digestion, although the
      effect of gastroduodenal digestion on its allergenicity has not been reported.
      OBJECTIVE: We sought to investigate the effect of gastric and gastroduodenal
      digestion on the allergenic activity of grape LTP. METHODS: The proteolytic
      stability of grape LTP was investigated by using an in vitro model of
      gastrointestinal digestion. The allergenicity of LTP and its digesta was assessed
      in vitro by means of IgE immunoblotting, RASTs, and in vivo skin prick tests in
      the same patients with grape allergy. RESULTS: Grape LTP was resistant to gastric
      digestion, and yielded a 6000-d relative molecular mass C-terminally trimmed
      fragment after duodenal digestion. This fragment retained the in vitro IgE
      reactivity of the intact protein. Inclusion of phosphatidylcholine during gastric
      digestion protected the LTP to a limited extent against digestion. Digestion did
      not affect the in vivo (skin prick test) biologic activity of LTP. CONCLUSION:
      The allergenic activity of grape LTP was highly resistant to in vitro digestion.
      This property might facilitate sensitization through the gastrointestinal tract
      and might also potentiate the ability of LTPs to elicit severe allergic reactions
      in sensitized individuals. CLINICAL IMPLICATIONS: Purified natural allergens will
      facilitate the development of component-resolved diagnostic approaches, including
      allergen chips. This study contributes to our understanding of the role digestion
      plays in symptom elicitation in true food allergy.

PMID- 16890776
TI  - Advances in basic and clinical immunology.
AB  - This review comments on basic and clinical immunology articles that were
      published in 2005, with a focus on those that appeared in the Journal of Allergy
      and Clinical Immunology. In the area of basic immunology, mechanisms of the
      innate immune system and its interaction with the adaptive immune system were
      described, with special consideration to applications in biodefense strategies. T
      regulatory cells were further characterized in their role for the control of
      allergic, autoimmune, and neoplastic disorders. The function of the thymus
      Hassall's corpuscles was reported to be the generation of T regulatory cells.
      Flavonoid molecules obtained from medicinal herbs, including astilbin and
      epigallocatechin gallate, were discovered to have immunomodulatory properties.
      Advances in clinical immunology resulted from efforts to develop a newborn
      screening test for severe combined immunodeficiency and the elucidation of the
      crystal structure of the IL-2 receptor gamma chain. Mutations in the membrane
      receptor transmembrane activator and calcium modulator and cyclophilin ligand
      interactor were found in patients with common variable immunodeficiency. New
      therapeutic options are described, such as the use of infliximab for granulomas
      and GM-CSF for chronic ulcers in patients with common variable immunodeficiency.
      The importance of mucosal immunity in acute HIV infection is cited, as is the
      role of CD8+ T-cell activation in HIV disease progression in children.

PMID- 16890775
TI  - Apple allergy across Europe: how allergen sensitization profiles determine the
      clinical expression of allergies to plant foods.
AB  - BACKGROUND: Allergy to a plant food can either result from direct sensitization
      to that food or from primary sensitization to pollen, latex, or another food.
      OBJECTIVE: We sought to investigate the primary sensitizers in apple allergy
      across Europe, the individual allergens involved, and whether these differences
      determine the clinical presentation. METHODS: Patients (n = 389) with positive
      case histories and skin prick test responses to fresh apple were selected in the
      Netherlands, Austria, Italy, and Spain. Skin prick tests and RASTs to a panel of
      pollens and plant foods were performed, as well as RASTs to Bet v 1 and the apple
      allergens Mal d 1, 2, 3, and 4. RESULTS: In the Netherlands, Austria, and Italy
      apple allergy is mild (>90% isolated oral symptoms) and related to birch
      pollinosis and sensitization to Bet v 1 and its apple homologue, Mal d 1, which
      has an odds ratio of local reactions of 2.85 (95% CI, 1.47-5.55). In Spain apple
      allergy is severe (>35% systemic reactions) and related to peach allergy and
      sensitization to Mal d 3 (nonspecific lipid transfer protein), which has an odds
      ratio of systemic reactions of 7.76 (95% CI, 3.87-15.56). CONCLUSION: The
      analysis of individual apple allergens in a clinical context has provided insight
      into the sensitization pathway and into the intrinsic risk an allergen bears to
      induce mild or severe food allergy. CLINICAL IMPLICATIONS: Information on the
      sensitization pathway is essential to develop preventive strategies in food
      allergy. The application of individual food allergens with a known intrinsic risk
      will improve the prognostic value of diagnostic tests.

PMID- 16890777
TI  - Immune cell transcriptome datasets reveal novel leukocyte subset-specific genes
      and genes associated with allergic processes.
AB  - BACKGROUND: The precise function of various resting and activated leukocyte
      subsets remains unclear. For instance, mast cells, basophils, and eosinophils
      play important roles in allergic inflammation but also participate in other
      immunologic responses. One strategy to understand leukocyte subset function is to
      define the expression and function of subset-restricted molecules. OBJECTIVE: To
      use a microarray dataset and bioinformatics strategies to identify novel
      leukocyte markers as well as genes associated with allergic or innate responses.
      METHODS: By using Affymetrix microarrays, we generated an immune transcriptome
      dataset composed of gene profiles from all of the major leukocyte subsets,
      including rare enigmatic subsets such as mast cells, basophils, and plasma cells.
      We also assessed whether analysis of genes expressed commonly by certain groups
      of leukocytes, such as allergic leukocytes, might identify genes associated with
      particular responses. RESULTS: Transcripts highly restricted to a single
      leukocyte subset were readily identified (>2000 subset-specific transcripts),
      many of which have not been associated previously with leukocyte functions.
      Transcripts expressed exclusively by allergy-related leukocytes revealed well
      known as well as novel molecules, many of which presumably contribute to allergic
      responses. Likewise, Nearest Neighbor Analysis of genes coexpressed with Toll
      like receptors identified genes of potential relevance for innate immunity.
      CONCLUSION: Gene profiles from all of the major human leukocyte subsets provide a
      powerful means to identify genes associated with single leukocyte subsets, or
      different types of immune response. CLINICAL IMPLICATIONS: A comprehensive
      dataset of gene expression profiles of human leukocytes should provide new
      targets or biomarkers for human inflammatory diseases.

PMID- 16890779
TI  - Redirection of allergen-specific TH2 responses by a modified adenine through Toll
      like receptor 7 interaction and IL-12/IFN release.
AB  - BACKGROUND: Natural or synthetic ligands of Toll-like receptors (TLRs), such as
      CpG-containing oligodeoxynucleotides and imidazoquinolines, affect the functional
      phenotype of antigen-specific human T lymphocytes by inducing cytokine release by
      cells of the innate immunity. OBJECTIVE: In vitro investigation of the ability of
      substitute adenines (SAs) to affect antigen-presenting cells and shift the
      functional phenotype of specific human T(H)2 cells was performed. METHODS: The
      functional profile of hapten- and allergen-specific T-cell lines obtained in the
      absence or presence of modified adenines was assessed by means of quantitative
      real-time PCR, flow cytometry, and ELISAs. Activation of TLRs was evaluated by
      means of nucleofection of HEK293 cells. RESULTS: The synthetic heterocycle,
      chemically related to adenine with substitution in positions 2-, 8-, and 9- (SA
      2), but not its related derivative lacking 2- and 8- substitutions, stimulated
      the production of high amounts of IL-12, IL-10, TNF-alpha, and IL-6 by CD14(+)
      cells and IFN-alpha and CXCL10 by blood dendritic cell antigen (BDCA)-4(+)
      plasmacytoid dendritic cells. A nuclear factor kappaB-dependent signaling pathway
      mediated by SA-2 ligation of TLR7 was responsible for these effects. SA-2 also
      redirected the in vitro differentiation of either Dermatophagoides pteronyssinus
      group 1 or amoxicillin-specific T(H)2 cells toward the T(H)1/T(H)0 phenotype,
      with parallel downregulation of GATA-3 and upregulation of T-box expressed in T
      cells transcription factors. CONCLUSION: Critical substitutions of the adenine
      backbone confer the ability to activate TLR7, inducing the production of
      modulatory cytokines able to shift human allergen-specific T(H)2 cells to a
      T(H)1/T(H)0 phenotype. CLINICAL IMPLICATIONS: Appropriately modified adenines
      might be used as effective adjuvants for the development of novel
      immunotherapeutic strategies of allergic disorders.

PMID- 16890778
TI  - Modulation of immunogenicity and allergenicity by controlling the number of
      immunostimulatory oligonucleotides linked to Amb a 1.
AB  - BACKGROUND: Immunostimulatory DNA sequences (ISS) are potent immunomodulators
      that can drive T(H)1 responses to antigens or allergens. This effect can be
      dramatically enhanced by direct linkage of ISS to the protein. OBJECTIVE:
      Evaluate the effects of the number of ISS bound to the major ragweed allergen Amb
      a 1 on immunogenicity and allergenicity. METHODS: Immunogenicity in mice and
      allergenicity using PBMC or sera from subjects with ragweed allergy were assayed.
      RESULTS: Both antibody induction in vivo and antibody recognition in vitro were
      highly sensitive to the number of ISSs linked. IgE recognition of Amb a 1 in
      competitive ELISA or histamine release assays was inhibited by ISS linkage and
      showed an inverse relationship to the number of ISSs bound. Type and magnitude of
      antibody induction in mice was also highly dependent on the number of ISS bound.
      At the highest ISS to protein ratios, antibody induction was very low. Moderate
      ISS to protein ratios induced high antibody responses in which IgG(2a) generally
      predominated. Low ISS to protein ratios produced the highest overall antibody
      responses in which IgG(1) predominated. In contrast, varied ISS to protein ratios
      did not affect T-cell responses. In both in vivo mouse studies and in vitro human
      PBMC studies, all ISS to protein ratios evaluated induced similar responses
      represented by high levels of IFN-gamma and low levels of T(H)2 cytokines.
      CONCLUSION: Controlling the number of ISS bound to a protein allows manipulation
      of antibody recognition and induction while retaining the potent T(H)1 properties
      of an ISS-linked protein. CLINICAL IMPLICATIONS: Immunostimulatory DNA sequence
      linked Amb a 1 conjugate represents a safe, novel therapeutic approach for
      treating ragweed allergy.

PMID- 16890780
TI  - Susceptibility of pediatric HIV-1 isolates to recombinant CD4-IgG2 (PRO 542) and
      humanized mAb to the chemokine receptor CCR5 (PRO 140).

PMID- 16890781
TI  - Duration of airborne Fel d 1 reduction after cat washing.

PMID- 16890782
TI  - Detection of novel occupational wood allergens in locust wood dust (Robinia
      pseudoacacia L.).

PMID- 16890783
TI  - Apparent sensitization to latex through swim caps.

PMID- 16890784
TI  - Aspiration before immunotherapy injection is not required.

PMID- 16890785
TI  - Recalcitrant warts, associated with natural killer cell dysfunction, treated with
      systemic IFN-alpha.

PMID- 16890786
TI  - Food intolerance and wheezing in young South Asian and white children: prevalence
      and clinical significance.

PMID- 16890788
TI  - Child-care center sandpits: a source of cat allergen (Fel d 1).

PMID- 16890787
TI  - Changes in specific IgE and IgG and monocyte chemoattractant protein-1 in workers
      with occupational asthma caused by diisocyanates and removed from exposure.

PMID- 16890789
TI  - Benzocaine anaphylaxis.

PMID- 16890790
TI  - Chemokine expression in allergic diseases.

PMID- 16890793
TI  - Epidermal growth factor receptor targeting in cancer.
AB  - The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase of the
      ErbB family that is abnormally activated in many epithelial tumors. Several
      mechanisms lead to the receptor's aberrant activation that is observed in cancer,
      including receptor overexpression, mutation, ligand-dependent receptor
      dimerization, and ligand-independent activation. Two classes of anti-EGFR agents
      are currently approved for the treatment of patients with cancer: cetuximab, a
      monoclonal antibody directed at the extracellular domain of the receptor, and
      gefitinib and erlotinib, oral, low-molecular-weight (MW), adenosine triphosphate
      (ATP)-competitive inhibitors of the receptor's tyrosine kinase. Anti-EGFR
      monoclonal antibodies have demonstrated activity in the therapy of advanced
      colorectal carcinoma and in a variety of epithelial tumor types, including head
      and neck cancer and non-small cell lung cancer (NSCLC). The development of low
      MW, anti-EGFR tyrosine kinase inhibitors (TKIs) has been focused until recently
      on NSCLC, although responses have been reported for other types of cancer.
      Erlotinib was the only agent approved based on demonstrating improved survival,
      which was observed in patients with advanced NSCLC who previously had been
      treated with chemotherapy. Recent major advances in the EGFR field include the
      discovery of EGFR somatic mutations in NSCLC that have important implications for
      biology, treatment, clinical trial design, and methods for mutation detection.
      Clinical and survival benefits with anti-EGFR agents have been demonstrated in
      additional tumor types such as head and neck and pancreatic carcinomas. New
      agents with clinical activity are entering the clinic and new combinatorial
      approaches with anti-EGFR agents are being explored. Major efforts are,
      belatedly, attempting to identify molecular markers that can predict patients
      more likely to respond to anti-EGFR therapy.

PMID- 16890794
TI  - Targeting HER2 Epitopes.
AB  - Variable expression of the HER2 receptor has been implicated in the pathogenesis
      of a number of malignancies. Many therapeutic modalities have been devised that
      target the receptor and downstream molecular pathways. The humanized monoclonal
      antibodies trastuzumab and pertuzumab bind epitopes on the extracellular domain,
      resulting in cell growth inhibition though a number of proposed mechanisms.
      Peptidomimetic agents represent short amino acid sequences containing structural
      features of the antibody complementarity determining regions (CDRs), and appear
      to have similar inhibitory properties in experimental models. RNA aptamers are
      ribonucleotide sequences that also exhibit complementarity with extracellular
      epitopes and lead to growth inhibition. Recent data suggest a synergistic
      interaction of HER2 epitope-targeting agents when used in combination.

PMID- 16890795
TI  - Role of Raf kinase in cancer: therapeutic potential of targeting the Raf/MEK/ERK
      signal transduction pathway.
AB  - Improvements in our understanding of the molecular basis of cancer have led to
      the clinical development of protein kinase inhibitors, which target pivotal
      molecules involved in intracellular signaling pathways implicated in
      tumorigenesis and progression. These novel targeted agents have demonstrated
      activity against a wide range of solid tumors, are generally better tolerated
      than standard chemotherapeutics, and may revolutionize the management of advanced
      refractory cancer. The ubiquitous Raf serine/threonine kinases are pivotal
      molecules within the Raf/mitogen extracellular kinase (MEK)/extracellular signal
      related kinase (ERK) signaling pathway, which regulates cellular proliferation
      and survival. Raf kinase isoforms (wild-type Raf-1 or the b-raf V600E oncogene)
      are overactivated in a variety of solid tumor types, including renal cell
      carcinoma (RCC), hepatocellular carcinoma (HCC), non-small cell lung cancer
      (NSCLC), melanoma, and papillary thyroid carcinoma. In this review, the role of
      Raf in normal cells and in cancer is discussed, and an overview is given of Raf
      inhibitors currently in development, focusing on sorafenib tosylate (BAY 43-9006
      or sorafenib). Sorafenib is the first oral multi-kinase inhibitor to be developed
      that targets Raf kinases (Raf-1, wild-type B-Raf, and b-raf V600E), in addition
      to receptor tyrosine kinases associated with angiogenesis (vascular endothelial
      growth factor receptor [VEGFR]-2/-3, platelet-derived growth factor receptor
      [PDGFR]-beta) or tumor progression (Flt-3, c-kit). Preclinical and clinical
      sorafenib data that led to its recent approval for the treatment of advanced RCC
      are summarized, along with current thinking on sorafenib's mechanism of effect on
      the tumor and tumor vasculature in melanoma and RCC.

PMID- 16890796
TI  - New paradigms in anticancer therapy: targeting multiple signaling pathways with
      kinase inhibitors.
AB  - Signal transduction in cancer cells is a sophisticated process that involves
      receptor tyrosine kinases (RTKs) that eventually trigger multiple cytoplasmic
      kinases, which are often serine/threonine kinases. A number of tumor models have
      identified several key cellular signaling pathways that work independently, in
      parallel, and/or through interconnections to promote cancer development. Three
      major signaling pathways that have been identified as playing important roles in
      cancer include the phosphatidyl inositol-3-kinase (PI3K)/AKT, protein kinase C
      (PKC) family, and mitogen-activated protein kinase (MAPK)/Ras signaling cascades.
      In clinical trials, highly selective or specific blocking of only one of the
      kinases involved in these signaling pathways has been associated with limited or
      sporadic responses. Improved understanding of the complexity of signal
      transduction processes and their roles in cancer has suggested that simultaneous
      inhibition of several key kinases at the level of receptors and/or downstream
      serine/threonine kinases may help to optimize the overall therapeutic benefit
      associated with molecularly targeted anticancer agents. Using targeted agents to
      inhibit multiple signaling pathways has emerged as a new paradigm for anticancer
      treatment based on preclinical and clinical data showing potent anti-tumor
      activity of single drugs inhibiting multiple molecular targets or combination
      therapies involving multiple drugs with selective or narrow target specificity.
      Preclinical and clinical studies point to molecules on vascular endothelial cells
      and pericytes as being important targets for anticancer therapies, as well as
      molecules on or within tumor cells themselves. This suggests that optimal
      therapeutic approaches to cancer may involve targeting multiple molecules found
      in both the tumor and supportive tissues. In this review, we will use the most
      recent preclinical and clinical data to describe this emerging paradigm for
      anticancer therapy involving targeting multiple signaling pathways with tyrosine
      or serine/threonine kinase inhibitors.

PMID- 16890797
TI  - Novel agents that target tublin and related elements.
AB  - The success of the taxanes and other agents that target tubulin and mitosis and
      their evolution to being mainstay constituents of both curative and palliative
      therapeutic regimens for a wide variety of malignancies have amplified efforts to
      discover anti-mitotic and anti-microtubule agents with greater therapeutic
      indices. A wide variety of structurally diverse compounds that have demonstrated
      broad and potent anti-tumor activity in preclinical evaluations are currently
      being evaluated in clinical investigations. This review will discuss the
      characteristics of novel taxanes and other agents that might confer clinical
      advantages relative to the anti-tubulin and anti-mitotic agents in clinical use.
      Besides taxanes with novel delivery systems and unique physicochemical
      characteristics, the epothilones and other natural products, as well as
      developmental therapeutics against new mitotic targets, will be reviewed.

PMID- 16890798
TI  - Tubulin-associated drug targets: Aurora kinases, Polo-like kinases, and others.
AB  - Unrestrained cell division in cancer cells is dependent upon mitosis and its
      related processes. Therefore, a proven effective strategy in cancer treatment has
      been to interfere with the function of the mitotic spindle. Despite the success
      of these anti-mitotic agents, tubulin itself remains the only spindle-associated
      protein targeted by clinically approved agents. However, in recent years major
      advances have been achieved in targeting proteins that associate with tubulin and
      the mitotic spindle. Mitotic kinases such as the Aurora and Polo families are
      receiving significant attention due to their vital roles in assuring proper
      centrosome separation and chromosome segregation. Indeed, potent and selective
      inhibitors of these kinases have entered clinical trials. Similarly, the
      kinesins, particularly kinesin spindle protein (KSP), have emerged as potential
      therapeutic targets and inhibitors of KSP are currently under evaluation in the
      clinic. Although inhibitors have not been reported, mitotic checkpoint kinases
      (Mad2) and separase are additional potential targets for therapeutic
      intervention. Continued investigation of mechanisms regulating mitotic events
      will likely reveal additional proteins and pathways that could be potentially
      targeted and thereby provide more effective therapeutic options for cancer
      patients.

PMID- 16890799
TI  - Targeting the Bcl-2 family in cancer therapy.
AB  - The targeting of anti-apoptotic members of the Bcl-2 family of proteins,
      especially Bcl-2, is the focus of efforts to modulate the intrinsic pathway of
      apoptosis and effect tumor death. Current understanding of the role of Bcl-2
      family proteins and strategies and recent developments in drug inhibitors of
      these proteins, particularly antisense oligonucleotides and targeted small
      molecules, are reviewed.

PMID- 16890800
TI  - Heat shock protein 90: a unique chemotherapeutic target.
AB  - A large body of work spanning the past decade has identified the molecular
      chaperone heat shock protein 90 (Hsp90) as a critical modulator of an extensive
      network of cellular signaling pathways. Many of the processes overseen by Hsp90
      are deregulated in tumor cells, including cell cycle control, gene transcription,
      and apoptotic signaling. Hsp90 inhibition offers the potential of accomplishing
      what most molecularly targeted anticancer therapies do not--the simultaneous
      disruption of multiple signaling events critical to tumor cell growth and
      survival. Indeed, small molecule inhibitors of Hsp90 function are actively being
      evaluated in the clinic as anticancer agents. In this review, we highlight the
      current understanding of Hsp90 biology as it relates to cancer and discuss the
      discovery, development, and clinical status of Hsp90 inhibitors as anticancer
      drugs.

PMID- 16890801
TI  - Preclinical and clinical development of novel agents that target the protein
      kinase C family.
AB  - Protein kinase C (PKC) family comprises more than 12 serine-/threonine-specific
      isoenzymes. PKC isoenzymes play a complex role in the transduction of signal from
      tyrosine kinase receptor modulating proliferation, cell cycle, apoptosis,
      invasion, differentiation, and senescence in both cancer cells and endothelial
      cells. Thereby, inhibition and/or activation of specific PKCs is thought to
      control tumor growth by interacting directly with cancer cells and indirectly by
      blocking tumor angiogenesis. Furthermore, PKCs are known to modulate multi-drug
      resistance, providing a rational for the combination of PKCs modulators with
      classical cytotoxic drugs. During the past few years, preclinical and clinical
      data with first-generation PKC inhibitors/activators provided insight that PKCs
      may indeed represent attractive targets for the discovery of small molecules with
      new anticancer properties. In this review, we will provide an overview on the
      current understanding of PKC participation in chemotherapeutic resistance, the
      possible implications in cancer treatment, and the potential of most recent PKC
      inhibitors in molecular cancer therapeutics.

PMID- 16890802
TI  - Survivin-dependent and -independent pathways and the induction of cancer cell
      death by tetra-O-methyl nordihydroguaiaretic acid.
AB  - The inhibitor of apoptosis protein (IAP) family encodes a group of Baculovirus
      IAP repeat domain (BIR)-containing proteins that suppress apoptosis. Some of the
      IAPs, survivin and XIAP in particular, are differentially overexpressed in many
      types of human cancer and are deemed attractive anticancer targets. Here we
      review the regulation of survivin expression and survivin's functions in both
      normal and cancerous cells, and some of the current survivin-targeted cancer
      therapy. We further discuss the possible mechanisms of tetra-O-methyl
      nordihydroguaretic acid (M(4)N), a global transcription inhibitor, in the
      induction of cancer cell death in tumors via survivin-dependent and -independent
      pathways.

PMID- 16890803
TI  - The hypoxic inducible stress response as a target for cancer drug discovery.
AB  - All solid tumors experience some degree of hypoxia. The response to the stress of
      hypoxia is mediated in large part by the hypoxia inducible factor-1 (HIF-1)
      transcription factor that increases the expression of a variety of genes that
      allow the tumor to survive and grow in the hostile hypoxic environment. Increased
      tumor HIF-1 has been correlated with increased angiogenesis, aggressive tumor
      growth, and poor patient prognosis. This has lead to the current interest in HIF
      1 as a cancer drug target. HIF-1 activity in tumors depends on the availability
      of the HIF-1alpha subunit, the levels of which increase under hypoxic conditions
      or through the activation of oncogenes and/or inactivation of tumor-suppressor
      genes. HIF-1alpha level and HIF-1 activity are regulated by multiple pathways
      involving transcription, translation, post-translational modification, and the
      interaction with other transcription factors. A number of agents have been
      reported to block HIF-1 activity, acting on all of these mechanisms. Not all of
      the agents have been shown to block tumor HIF-1 activity in vivo. Some have shown
      marked HIF-1 inhibition and anti-tumor activity. There are agents already, or
      soon to be, tested in the clinic as anti-tumor inhibitors of HIF-1. The
      challenges will be to determine whether the effects of these agents that are seen
      is due to HIF-1 inhibition and to identify which patients are most likely to
      benefit from treatment with HIF-1 inhibitors.

PMID- 16890805
TI  - Targeting loss-of-function mutations in tumor-suppressor genes as a strategy for
      development of cancer therapeutic agents.
AB  - Two types of genetic mutations, gain-of-function in oncogenes and loss-of
      function in tumor-suppressor genes, are important molecular bases of
      tumorigenesis of human cancers. Target-based drug discovery is the main stream of
      contemporary cancer therapeutic development but largely focuses on gain-of
      function mutations in oncogenes. Loss-of-function mutations in tumor-suppressor
      genes are often neglected as therapeutic targets. In this review, we discuss the
      feasibility of targeting loss-of-function mutations in tumor-suppressor genes for
      the identification of cancer-specific therapeutic agents.

PMID- 16890806
TI  - The business of HIV/AIDS.

PMID- 16890804
TI  - Drug targeting of the c-MYC promoter to repress gene expression via a G
      quadruplex silencer element.
AB  - In this review, we describe the evidence for a parallel-stranded G-quadruplex in
      the purine-rich strand of the nuclease hypersensitivity element III(1) (NHE
      III(1)) of the promoter of c-MYC upstream of the P1 and P2 promoters. This
      biologically relevant G-quadruplex is a mixture of four loop isomers. The folding
      pattern of a nuclear magnetic resonance (NMR)-derived structure for the
      predominant loop isomer of this G-quadruplex has been obtained. This G-quadruplex
      has been demonstrated to be a silencer element, and the cationic porphyrin TMPyP4
      has been shown to stabilize this G-quadruplex. Furthermore, TMPyP4 has been shown
      to repress c-MYC expression, and this effect is mediated through the silencer
      element. Last, the in vivo activity of TMPyP4 in xenograph models is presented.

PMID- 16890807
TI  - Betting on HIV prevention.

PMID- 16890808
TI  - The devastating effects of HIV/AIDS on children.

PMID- 16890809
TI  - AIDS anniversaries in 2006 mark the time to deliver.

PMID- 16890810
TI  - HAART's first decade: success brings further challenges.

PMID- 16890811
TI  - What does absorption capacity not measure?

PMID- 16890812
TI  - Beyond stigma: social responses to HIV in South Africa.

PMID- 16890814
TI  - HIV/AIDS harm reduction in Iran.

PMID- 16890813
TI  - Microbicides: stopping HIV at the gate.

PMID- 16890815
TI  - Fight AIDS as well as the brain drain.

PMID- 16890816
TI  - Ernest Darkoh: confronting the challenge of HIV/AIDS in Africa.

PMID- 16890817
TI  - Scaling up antiretroviral treatment in resource-poor settings.

PMID- 16890818
TI  - Scaling up antiretroviral treatment in resource-poor settings.

PMID- 16890819
TI  - Scaling up antiretroviral treatment in resource-poor settings.

PMID- 16890820
TI  - Coordinating HIV control efforts.

PMID- 16890821
TI  - Russia, the G8, and HIV.

PMID- 16890822
TI  - Informing children of their HIV status.

PMID- 16890823
TI  - ESPRIT trial.

PMID- 16890824
TI  - ESPRIT trial.

PMID- 16890825
TI  - ESPRIT trial.

PMID- 16890826
TI  - ESPRIT trial.

PMID- 16890828
TI  - Heart disease in Africa.

PMID- 16890829
TI  - Preventing scientific misconduct.

PMID- 16890830
TI  - WHO: strengthening the road to renewal.

PMID- 16890831
TI  - HIV treatment response and prognosis in Europe and North America in the first
      decade of highly active antiretroviral therapy: a collaborative analysis.
AB  - BACKGROUND: Highly active antiretroviral therapy (HAART) for the treatment of HIV
      infection was introduced a decade ago. We aimed to examine trends in the
      characteristics of patients starting HAART in Europe and North America, and their
      treatment response and short-term prognosis. METHODS: We analysed data from
      22,217 treatment-naive HIV-1-infected adults who had started HAART and were
      followed up in one of 12 cohort studies. The probability of reaching 500 or less
      HIV-1 RNA copies per mL by 6 months, and the change in CD4 cell counts, were
      analysed for patients starting HAART in 1995-96, 1997, 1998, 1999, 2000, 2001,
      and 2002-03. The primary endpoints were the hazard ratios for AIDS and for death
      from all causes in the first year of HAART, which were estimated using Cox
      regression. RESULTS: The proportion of heterosexually infected patients increased
      from 20% in 1995-96 to 47% in 2002-03, and the proportion of women from 16% to
      32%. The median CD4 cell count when starting HAART increased from 170 cells per
      muL in 1995-96 to 269 cells per muL in 1998 but then decreased to around 200
      cells per muL. In 1995-96, 58% achieved HIV-1 RNA of 500 copies per mL or less by
      6 months compared with 83% in 2002-03. Compared with 1998, adjusted hazard ratios
      for AIDS were 1.07 (95% CI 0.84-1.36) in 1995-96 and 1.35 (1.06-1.71) in 2002-03.
      Corresponding figures for death were 0.87 (0.56-1.36) and 0.96 (0.61-1.51).
      INTERPRETATION: Virological response after starting HAART improved over calendar
      years, but such improvement has not translated into a decrease in mortality.

PMID- 16890832
TI  - CD4-guided scheduled treatment interruptions compared with continuous therapy for
      patients infected with HIV-1: results of the Staccato randomised trial.
AB  - BACKGROUND: Stopping antiretroviral therapy in patients with HIV-1 infection can
      reduce costs and side-effects, but carries the risk of increased immune
      suppression and emergence of resistance. METHODS: 430 patients with CD4-positive
      T-lymphocyte (CD4) counts greater than 350 cells per muL, and viral load less
      than 50 copies per mL were randomised to continued therapy (n=146) or scheduled
      treatment interruptions (n=284). Median time on randomised treatment was 21.9
      months (range 16.4-25.3). Primary endpoints were proportion of patients with
      viral load less than 50 copies per mL at the end of the trial, and amount of
      drugs used. Analysis was intention-to-treat. This study is registered at
      ClinicalTrials.gov with the identifier NCT00113126. FINDINGS: Drug savings in the
      scheduled treatment interruption group, compared with continuous treatment,
      amounted to 61.5%. 257 of 284 (90.5%) patients in the scheduled treatment
      interruption group reached a viral load less than 50 copies per mL, compared with
      134 of 146 (91.8%) in the continued treatment group (difference 1.3%, 95% CI-4.3
      to 6.9, p=0.90). No AIDS-defining events occurred. Diarrhoea and neuropathy were
      more frequent with continuous treatment; candidiasis was more frequent with
      scheduled treatment interruption. Ten patients (2.3%) had resistance mutations,
      with no significant differences between groups. INTERPRETATION: Drug savings with
      scheduled treatment interruption were substantial, and no evidence of increased
      treatment resistance emerged. Treatment-related adverse events were more frequent
      with continuous treatment, but low CD4 counts and minor manifestations of HIV
      infection were more frequent with scheduled treatment interruption.

PMID- 16890833
TI  - Durable efficacy of tipranavir-ritonavir in combination with an optimised
      background regimen of antiretroviral drugs for treatment-experienced HIV-1
      infected patients at 48 weeks in the Randomized Evaluation of Strategic
      Intervention in multi-drug reSistant patients with Tipranavir (RESIST) studies:
      an analysis of combined data from two randomised open-label trials.
AB  - BACKGROUND: Treatment options for HIV-1 infected individuals who have received
      extensive previous antiretroviral therapy are limited. We compared efficacy and
      safety of the novel non-peptidic protease inhibitor tipranavir co-administered
      with ritonavir plus an optimised background regimen with that of an investigator
      selected ritonavir-boosted comparator protease inhibitor (CPI-ritonavir) in such
      patients. METHODS: We did a combined analysis of 48-week data from two ongoing,
      randomised, open-label, multinational, phase III, RESIST studies. HIV-1-infected
      adults with 3 months or longer previous triple antiretroviral class experience,
      two or more previous protease inhibitor regimens, HIV-1 RNA 1000 copies per mL or
      greater, and genotypically demonstrated primary resistance to protease inhibitor,
      were eligible. Primary endpoints were proportion of treatment responders (with
      reduction in viral load of 1 log(10) copies per mL or greater below baseline
      without treatment change) at 48 weeks and time to treatment failure through 48
      weeks (intention-to-treat analysis). The RESIST studies are registered with
      ClinicalTrials.gov, numbers NCT00054717 (RESIST-1) and NCT00144170 (RESIST-2).
      FINDINGS: 3324 patients were screened; 746 received tipranavir-ritonavir and 737
      CPI-ritonavir. 486 (65.1%) patients on tipranavir-ritonavir and 192 (26.1%) on
      CPI-ritonavir remained on assigned treatment until week 48. At week 48, more
      patients achieved and maintained treatment response in the tipranavir-ritonavir
      group than in the CPI-ritonavir group (251 [33.6%] vs 113 [15.3%]; p<0.0001).
      Median time to treatment failure was significantly longer in the tipranavir
      ritonavir group than in the CPI-ritonavir group (113 days vs 0 days; p<0.0001).
      Gastrointestinal system disorders and raised transaminase, cholesterol, and
      triglycerides were more frequent in the tipranavir-ritonavir group than in the
      CPI-ritonavir group. INTERPRETATION: Compared with CPI-ritonavir, tipranavir
      ritonavir with an optimised background regimen provides better virological and
      immunological responses over 48 weeks in patients who have received extensive
      previous antiretroviral treatment.

PMID- 16890834
TI  - The KLEAN study of fosamprenavir-ritonavir versus lopinavir-ritonavir, each in
      combination with abacavir-lamivudine, for initial treatment of HIV infection over
      48 weeks: a randomised non-inferiority trial.
AB  - BACKGROUND: Lopinavir-ritonavir is a preferred protease inhibitor co-formulation
      for initial HIV-1 treatment. Fosamprenavir-ritonavir has shown similar efficacy
      and safety to lopinavir-ritonavir when each is combined with two nucleoside
      reverse transcriptase inhibitors. We compared the two treatments directly in
      antiretroviral-naive patients. METHODS: This open-label, non-inferiority study
      included 878 antiretroviral-naive, HIV-1-infected patients randomised to receive
      either fosamprenavir-ritonavir 700 mg/100 mg twice daily or lopinavir-ritonavir
      400 mg/100 mg twice daily, each with the co-formulation of abacavir-lamivudine
      600 mg/300 mg once daily. Primary endpoints were proportion of patients achieving
      HIV-1 RNA less than 400 copies per mL at week 48 and treatment discontinuations
      because of an adverse event. The intent-to-treat analysis included all patients
      exposed to at least one dose of randomised study medication. This study is
      registered with ClinicalTrials.gov, number NCT00085943. FINDINGS: At week 48, non
      inferiority of fosamprenavir-ritonavir to lopinavir-ritonavir (95% CI around the
      treatment difference -4.84 to 7.05) was shown, with 315 of 434 (73%) patients in
      the fosamprenavir-ritonavir group and 317 of 444 (71%) in the lopinavir-ritonavir
      group achieving HIV-1 RNA less than 400 copies per mL. Treatment discontinuations
      due to an adverse event were few and occurred with similar frequency in the two
      treatment groups (fosamprenavir-ritonavir 53, 12%; lopinavir-ritonavir 43, 10%).
      Diarrhoea, nausea, and abacavir hypersensitivity were the most frequent drug
      related grade 2-4 adverse events. Treatment-emergent drug resistance was rare; no
      patient had virus that developed reduced susceptibility to fosamprenavir
      ritonavir or lopinavir-ritonavir. INTERPRETATION: Fosamprenavir-ritonavir twice
      daily in treatment-naive patients provides similar antiviral efficacy, safety,
      tolerability, and emergence of resistance as lopinavir-ritonavir, each in
      combination with abacavir-lamivudine.

PMID- 16890835
TI  - Absorptive capacity and disbursements by the Global Fund to Fight AIDS,
      Tuberculosis and Malaria: analysis of grant implementation.
AB  - BACKGROUND: The Global Fund to Fight AIDS, Tuberculosis and Malaria was launched
      in 2002 to attract and rapidly disburse money to fight these diseases. However,
      some commentators believe that poor countries cannot effectively use such
      resources to increase delivery of their health programmes-referred to as a lack
      of absorptive capacity. We aimed to investigate the major determinants of grant
      implementation in developing countries. METHODS: With information available
      publicly on the Global Fund's website, we did random-effects analysis to
      investigate the effect of grant characteristics, types of primary recipient and
      local fund agent, and country attributes on disbursements that were made between
      2003 and 2005 (phase one of Global Fund payments). To check the robustness of
      findings, regression results from alternative estimation methods and model
      specifications were also tested. FINDINGS: Grant characteristics--such as size of
      commitment, lag time between signature and first disbursement, and funding round
      had significant effects on grant implementation. Enhanced political stability was
      associated with high use of grants. Low-income countries, and those with less
      developed health systems for a given level of income, were more likely to have a
      higher rate of grant implementation than nations with higher incomes or more
      developed health systems. INTERPRETATION: The higher rate of grant implementation
      seen in countries with low income and low health-spending lends support to
      proponents of major increases in health assistance for the poorest countries and
      argues that focusing resources on low-income nations, particularly those with
      political stability, will not create difficulties of absorptive capacity. Our
      analysis was restricted to grant implementation, which is one part of the issue
      of absorptive capacity. In the future, assessment of the effect of Global Fund
      grants on intervention coverage will be vital.

PMID- 16890837
TI  - The WHO public-health approach to antiretroviral treatment against HIV in
      resource-limited settings.
AB  - WHO has proposed a public-health approach to antiretroviral therapy (ART) to
      enable scaling-up access to treatment for HIV-positive people in developing
      countries, recognising that the western model of specialist physician management
      and advanced laboratory monitoring is not feasible in resource-poor settings. In
      this approach, standardised simplified treatment protocols and decentralised
      service delivery enable treatment to be delivered to large numbers of HIV
      positive adults and children through the public and private sector. Simplified
      tools and approaches to clinical decision-making, centred on the "four Ss"--when
      to: start drug treatment; substitute for toxicity; switch after treatment
      failure; and stop--enable lower level health-care workers to deliver care. Simple
      limited formularies have driven large-scale production of fixed-dose combinations
      for first-line treatment for adults and lowered prices, but to ensure access to
      ART in the poorest countries, the care and drugs should be given free at point of
      service delivery. Population-based surveillance for acquired and transmitted
      resistance is needed to address concerns that switching regimens on the basis of
      clinical criteria for failure alone could lead to widespread emergence of drug
      resistant virus strains. The integrated management of adult or childhood illness
      (IMAI/IMCI) facilitates decentralised implementation that is integrated within
      existing health systems. Simplified operational guidelines, tools, and training
      materials enable clinical teams in primary-care and second-level facilities to
      deliver HIV prevention, HIV care, and ART, and to use a standardised patient
      tracking system.

PMID- 16890838
TI  - Vaccines to prevent transmission of HIV-1 via breastmilk: scientific and
      logistical priorities.
AB  - Mother-to-child transmission (MTCT) of HIV-1 is the major mode of paediatric
      infection. The rapidly increasing incidence of MTCT worldwide has resulted in an
      urgent need for preventive strategies. Antiretroviral regimens can prevent
      intrapartum HIV transmission; however, these regimens do not prevent HIV
      transmission through breastfeeding. Furthermore, children who escape MTCT are
      again at risk of infection when they become sexually active as adolescents. An
      infant vaccine regimen, begun at birth, would hence be a more attractive strategy
      and might also provide the basis for lifetime protection. Unique features of MTCT
      and paediatric HIV disease could be helpful in understanding correlates of immune
      protection and could facilitate rapid assessment of vaccine efficacy. Thus, there
      is compelling rationale to develop safe, effective HIV vaccines for use in
      infants and children. Here, we discuss the scientific and logistical challenges
      for the development of paediatric HIV vaccines; available vaccines and completed
      or planned paediatric vaccine trials are also discussed.

PMID- 16890839
TI  - Circumcision and HIV prevention research: an ethical analysis.

PMID- 16890836
TI  - HIV/AIDS epidemiology, pathogenesis, prevention, and treatment.
AB  - The HIV-1 pandemic is a complex mix of diverse epidemics within and between
      countries and regions of the world, and is undoubtedly the defining public-health
      crisis of our time. Research has deepened our understanding of how the virus
      replicates, manipulates, and hides in an infected person. Although our
      understanding of pathogenesis and transmission dynamics has become more nuanced
      and prevention options have expanded, a cure or protective vaccine remains
      elusive. Antiretroviral treatment has transformed AIDS from an inevitably fatal
      condition to a chronic, manageable disease in some settings. This transformation
      has yet to be realised in those parts of the world that continue to bear a
      disproportionate burden of new HIV-1 infections and are most affected by
      increasing morbidity and mortality. This Seminar provides an update on
      epidemiology, pathogenesis, treatment, and prevention interventions pertinent to
      HIV-1.

PMID- 16890840
TI  - AIDS: from crisis management to sustained strategic response.

PMID- 16890841
TI  - The case for expanding access to highly active antiretroviral therapy to curb the
      growth of the HIV epidemic.

PMID- 16890842
TI  - An examination of the Global Fund at 5 years.

PMID- 16890843
TI  - The 10-year struggle to provide antiretroviral treatment to people with HIV in
      the developing world.

PMID- 16890845
TI  - Persistent pyrexia and plaques: a perplexing puzzle.

PMID- 16890844
TI  - HAART for the HIV-infected employees of large companies in Africa.

PMID- 16890846
TI  - Re: Endovascular abdominal aortic aneurysm repair.

PMID- 16890848
TI  - Aortic necks of ruptured abdominal aneurysms dilate more than asymptomatic
      aneurysms after endovascular repair.
AB  - BACKGROUND: Endovascular repair of abdominal aortic aneurysm (AAA) is
      increasingly used. We evaluated if a difference exists in the rate of change of
      the aortic neck diameter between non-ruptured and ruptured AAAs after
      endovascular aneurysm repair (EVAR). METHODS: Details of patients undergoing
      elective (group I) and emergency (group II) EVAR using Talent stents between
      October 1999 and September 2005 were reviewed. Top neck diameters were
      prospectively recorded on the hospital database from computed tomography scans
      preoperatively and at 1, 3, 12, and 24 months postoperatively. The aortic neck
      diameter rate of change was calculated for each group. RESULTS: Endovascular
      repair was performed on 110 elective and 41 emergency patients, of which 100 (80
      male) elective and 29 (26 male) emergency patients were included in this
      analysis. Mean age was similar in each group. Stents were oversized by 20.9% +/-
      13.6% in group I and by 24.7% +/- 16.3% in group II (P = .37). The preoperative
      mean proximal aortic neck was larger in group II (25.0 +/- 3.3 mm vs 23.5 +/- 2.8
      mm; P = .029). The growth rate of the top neck diameter was significantly greater
      at 12 months (1.48 +/- 2.4 mm/year vs 3.89 +/- 6.24 mm/year; P = .04) and 24
      months (.99 +/- 1.1 mm/year vs 2.61 +/- 3.3 mm/year; P = .04) in group II than in
      group I. A decreasing sac size was found in 68.2% of patients whose neck dilated.
      The complication rate was similar in each group. CONCLUSION: Aneurysm necks in
      patients with ruptured aneurysms are larger and dilate at a greater rate than
      those with nonruptured aneurysms. The accelerated rate of expansion in some
      patients must be borne in mind during follow-up and in secondary endovascular
      interventions and conversion to open surgery.

PMID- 16890847
TI  - Increasing incidence of ruptured abdominal aortic aneurysm: a population-based
      study.
AB  - OBJECTIVE: The aim of the present population-based study was to assess the trends
      of age- and gender-specific incidence of ruptured abdominal aortic aneurysm
      (rAAA). METHODS: Patients with rAAA from the city of Malmo, Sweden, were studied
      between 2000 and 2004. An analysis of trends of incidence and mortality of rAAA
      in Malmo was possible because of a previous population-based study on patients
      with rAAA between 1971 and 1986 (autopsy rate 85% compared with 25% for the time
      period 2000 to 2004). The in-hospital registry of Malmo University Hospital and
      the databases at the Department of Pathology, Malmo, and the Institution of
      Forensic Medicine, Lund, identified patients with rAAA, and the in-hospital
      registry identified all elective repairs for AAA. RESULTS: Compared with the time
      period 1971 to 1986, the overall incidence of rAAA significantly increased from
      5.6 (95 % confidence interval [CI], 4.9 to 6.3) to 10.6 (95% CI, 8.9 to 12.4) per
      100,000 person-years (standardized mortality ratio, 1.6; 95% CI, 1.0 to 2.1). In
      men aged 60 to 69 and 70 to 79 years, the incidence increased significantly from
      16 (95% CI, 11 to 21) and 56 (95% CI, 43 to 69) to 46 (95% CI, 28 to 63) and 117
      (95% CI, 84 to 149) per 100,000 person-years, respectively, whereas no increase
      in the age-specific incidence in women could be demonstrated. The overall
      incidence of elective repair of AAA increased significantly from 3.4 (95% CI, 2.8
      to 4.0) to 7.0 (95% CI, 5.6 to 8.4) per 100,000 person-years and increased most
      significantly from 12 (95% CI, 3.4 to 32) to 68 (95% CI, 34 to 102) per 100,000
      person-years in men aged 80 to 89 years and from 5.1 (95% CI, 2.4 to 9.3) to 28
      (95% CI, 15 to 41) per 100,000 person-years in women aged 70 to 79 years. The
      elective-acute repair ratio in women increased from 2.4 to 5.6 and decreased in
      men from 2.1 to 1.0. CONCLUSIONS: Between 1971 to 1986 and 2000 to 2004, the
      incidence of rAAA increased significantly, despite a 100% increase in elective
      repairs and notwithstanding a potential for bias towards underestimation due to
      lower autopsy rates in recent years. The reason behind this increase is unclear,
      and further studies are needed to identify risk groups for direction of effective
      prevention and screening.

PMID- 16890849
TI  - Evolving strategies for the treatment of aortoenteric fistulas.
AB  - BACKGROUND: Aortoenteric fistulas (AEFs) are a rare but often fatal cause of
      gastrointestinal bleeding. Operative repair of AEF has been historically
      associated with extremely high morbidity and mortality. We reviewed our
      experience of open surgical and endovascular treatment of AEF to compare outcomes
      over a contemporaneous time period. METHODS: Over a 9-year period between January
      1997 and January 2006, 16 patients (11 men and 5 women) were diagnosed with and
      treated for AEFs. Seven patients underwent open surgical repair, and nine, with
      anatomically suitable lesions, underwent endovascular repair. The outcome after
      treatment of these patients was investigated for survival, perioperative
      complications, length of hospital stay, and long-term disposition. RESULTS: Three
      primary and 13 secondary AEFs were treated. The mean time from the initial aortic
      operation until AEF diagnosis was 5.9 years (range, 0.7-12.2 years) for patients
      with secondary AEFs. The overall 30-day mortality rate was 18.8%. One
      intraoperative death and one in-hospital death secondary to multisystem organ
      failure occurred in patients undergoing open repair. One in-hospital death
      related to persistent sepsis occurred in the endovascular group. The overall
      perioperative complication rate was 50.0%. Complications in the open group
      included sepsis, renal failure, bowel obstruction, and pancreatitis.
      Complications in the endovascular group were related to persistent sepsis. The
      mean in-hospital length of stay was significantly longer for patients undergoing
      open repair compared with endovascular repair (44.0 vs 19.4 days; P = .04). Four
      (80%) of five patients who were discharged from the hospital in the open group
      were placed in skilled nursing facilities, and seven (87.5%) of eight patients
      discharged in the endovascular group returned home. The median overall survival
      after hospital discharge was 23.1 months. There were no late aneurysm-related
      deaths or late deaths related to septic complications. CONCLUSIONS: Patients with
      AEFs have limited overall survival. Endovascular therapy offers an alternative to
      open surgical repair, seems to be associated with decreased perioperative
      morbidity and mortality and a shorter in-hospital stay, and allows for acceptable
      survival given the presence of coexisting medical comorbidities. Furthermore,
      endovascular repair provides a therapeutic option to control bleeding and allow
      for continued intervention in a stabilized setting.

PMID- 16890850
TI  - Protected carotid stenting in high-surgical-risk patients: the ARCHeR results.
AB  - BACKGROUND: Carotid endarterectomy is the standard of care for most patients with
      severe extracranial carotid bifurcation disease. However, its safety and efficacy
      in patients with significant surgical risk are unclear. The ARCHeR (ACCULINK for
      Revascularization of Carotids in High-Risk patients) trial was performed to
      determine whether carotid artery stenting with embolic protection is a safe and
      effective alternative to endarterectomy in high-surgical-risk patients. METHODS:
      The ARCHeR trial is a series of three sequential, multicenter, nonrandomized,
      prospective studies. Forty-eight sites enrolled 581 high-surgical-risk patients
      between May 2000 and September 2003. Patients with severe carotid artery stenosis
      (angiographically defined, symptomatic > or =50%, or asymptomatic > or =80%) had
      an ACCULINK nitinol stent implanted. The ACCUNET filter embolic protection system
      was added to the procedure in the final 2 studies (422 patients). The primary
      efficacy end point was a composite of periprocedural (< or =30 days) death,
      stroke, and myocardial infarction, plus ipsilateral stroke between days 31 and
      365. RESULTS: The 30-day rate of death/stroke/myocardial infarction was 8.3% (95%
      confidence interval [CI], 6.2%-10.8%), and that of stroke/death was 6.9% (95% CI,
      5.0%-9.3%). Most (23/32) strokes were minor, of which more than half (12/23)
      returned to baseline National Institutes of Health Stroke Scale scores within 30
      days. The 30-day major/fatal stroke rate was 1.5% (95% CI, 0.7%-2.9%). No
      hemorrhagic strokes were observed in the study. Ipsilateral cerebrovascular
      accident occurred in 1.3% between 30 days and 1 year, thus giving a primary
      composite end point of 30-day death/stroke/myocardial infarction plus ipsilateral
      stroke at 1 year of 9.6% (95% CI, 7.2%-12.0%), which is below the 14.4%
      historical control comparator. Target lesion revascularization at 12 months and 2
      years was 2.2% and 2.9%, respectively. CONCLUSIONS: The ARCHeR results
      demonstrate that extracranial carotid artery stenting with embolic filter
      protection is not inferior to historical results of endarterectomy and suggest
      that carotid artery stenting is a safe, durable, and effective alternative in
      high-surgical-risk patients.

PMID- 16890851
TI  - Re: Protected carotid stenting.

PMID- 16890852
TI  - Clinical outcomes and cost comparison of carotid artery angioplasty with stenting
      versus carotid endarterectomy.
AB  - BACKGROUND: Recently, carotid angioplasty with stenting (CAS) has evolved as an
      alternative to carotid endarterectomy (CEA) for the treatment of carotid
      occlusive disease. Some concerns have arisen regarding the high cost of stents
      and neuroprotection devices, which may inflate the overall procedural costs
      relative to CEA. We report here a review and analysis contrasting the clinical
      outcomes and associated hospital costs incurred for patients treated with either
      CAS or CEA. METHODS: Ninety-four consecutive patients with surgically amenable
      carotid stenosis were offered CAS or CEA. Forty-six patients elected CAS, and 48
      patients underwent CEA. CAS was performed with the Smart Precise or Acculink
      stents, and all procedures included neuroprotection (Filter Wire or Accunet). CEA
      was performed with patients under general anesthesia with routine shunting and
      with Dacron or bovine pericardium patches. Clinical outcomes such as
      perioperative mortality, major adverse events (myocardial infarction, stroke, and
      death), length of stay, and the incidence of hemodynamic instability were
      analyzed. Total costs, indirect costs, and direct procedural costs associated
      with hospitalization were also reviewed. RESULTS: CAS was associated with a
      shorter length of stay compared with CEA (1.2 vs 2.1 days; P = .02). Differences
      in perioperative mortality (0% vs 2%; P = NS), major adverse events (2% vs 10%; P
      = .36), strokes (2% vs 4%; P = NS), myocardial infarctions (0% vs 4%; P = .49),
      and hypotension necessitating pressor support (21% vs 18%; P = NS) were not
      statistically significant. By using cost to charge ratio methodology according to
      the Medicare report, CAS was associated with higher total procedural costs (US
      dollars 17,402 vs US dollars 12,112; P = .029) and direct costs (US dollars
      10,522 vs US dollars 7227; P = .017). The differences in indirect costs were not
      significant (US dollars 6879 vs US dollars 4885; P = .063). CONCLUSIONS: CAS with
      neuroprotection was associated with clinical outcomes equivalent to those with
      CEA but had higher total hospital costs. These higher costs reflect the addition
      of expensive devices that have improved the technical success and the clinical
      outcomes associated with CAS.

PMID- 16890853
TI  - Gastric exercise tonometry: the key investigation in patients with suspected
      celiac artery compression syndrome.
AB  - INTRODUCTION: Controversy continues about the mere existence of the celiac artery
      compression syndrome. Earlier results of treatment of unselected patients groups
      showed varying, mostly disappointing, results. The recently introduced gastric
      exercise tonometry test is able to identify patients with actual gastrointestinal
      ischemia. We prospectively studied the use of gastric exercise tonometry as a key
      criterion for revascularization treatment in patients with otherwise unexplained
      abdominal complaints and significant stenosis of the celiac artery by compression
      of the arcuate ligament. METHODS: Patients were prospectively selected using
      abdominal artery angiography and gastric exercise tonometry. Patients with a
      significant compression of the celiac artery, typical abdominal complaints, and
      abnormal tonometry were considered for revascularization. RESULTS: Over a 7-year
      period, 43 patients with significant celiac artery compression were included in
      this study, and 30 patients were diagnosed as ischemic. Twenty-nine patients had
      revascularization, 22 (76 %) had a trunk release only. After a median follow-up
      of 39 months, 83% of patients were free of symptoms. The repeated tonometry after
      treatment improved in 100% of patients free of symptoms, compared with 25% in
      patients with persistent complaints after revascularization. CONCLUSIONS: The
      results of this study suggest that the celiac axis compression syndrome exists
      and that the actual ischemia can be detected by gastric exercise tonometry and
      treated safely, with success.

PMID- 16890854
TI  - Endoscopic versus open saphenous vein harvest for femoral to below the knee
      arterial bypass using saphenous vein graft.
AB  - BACKGROUND: Although the use of endoscopic vein harvest (EVH) in coronary artery
      bypass grafting is accepted, few studies have documented the implementation of
      EVH in peripheral vascular disease surgery. We hypothesized that EVH improves
      outcomes compared with open vein harvest (OVH) in patients undergoing femoral to
      below the knee arterial bypass surgery. METHODS: The charts of 144 consecutive
      patients undergoing infrainguinal bypass surgery over the course of 27 months
      were reviewed. A femoral to below the knee arterial bypass with saphenous vein
      was done in 88 patients (29 had EVH, 59 had OVH). The preoperative
      characteristics evaluated were age, gender, renal function, history of diabetes,
      hypertension, tobacco use, and previous infrainguinal bypass surgery on the
      affected side. End points included wound complications, length of hospital stay,
      operative time, angiographic and operative interventions for graft occlusion,
      patency rates, limb salvage, acute renal failure, myocardial infarction, and
      death. RESULTS: Patient characteristics and demographics were similar in the EVH
      and OVH groups. No operative intervention for occlusion was required in the EVH
      group (0/29) compared with 13.4% in the OVH group (8/59) (P = .03). At the mean
      follow-up time of 21 months, primary patency rate was 92.8% in the EVH group and
      80.6% in the OVH group (P = .12). No significant differences were found between
      the EVH and OVH groups in postoperative complications, length of hospital stay,
      operative time, patency rates, limb salvage, and death. CONCLUSION: Despite our
      initial concerns of damaging the venous conduit with a minimally invasive
      approach to saphenous vein harvest, EVH in our experience has resulted in a trend
      toward improved patency rates and decreased infectious wound complications while
      affording the benefit of improved cosmesis. An endoscopic approach results in
      smaller incisions, decreased interventions for occlusion, and improved outcomes
      compared with OVH. EVH is the procedure of choice for harvesting saphenous vein
      for femoral to below the knee arterial bypass surgery.

PMID- 16890859
TI  - Changing pattern of surgical revascularization for critical limb ischemia over 12
      years: endovascular vs. open bypass surgery.
AB  - OBJECTIVE: This study is a review and evaluation of our 12-year experience of
      revascularization for critical limb ischemia (CLI) with angioplasty/stenting and
      bypass surgery to identify specific trends of procedure volume and outcomes in
      this particular group. METHODS: Endovascular and open bypass procedures done for
      CLI by a single surgeon between 1993 and 2004 were evaluated retrospectively.
      Thrombolysis and thrombectomy procedures done as the only revascularization
      procedure were excluded from analysis. The data were divided into three groups by
      time periods: the first period, 1993 to 1996; the second period, 1997 to 2000;
      and the third period, 2001 to 2004. Outcomes were defined according to the
      reporting standards of the Society for Vascular Surgery/International Society for
      Cardiovascular Surgery. The study included 416 procedures done in 237 limbs in
      192 patients. The mean follow-up was 23 months (range, 1 to 122 months). RESULTS:
      Primary revascularization procedures for CLI were angioplasty in 153 limbs (65%)
      and bypass surgery in 84 (35%). Subsequent procedures were angioplasty in 102
      limbs (57%) and open surgery (bypass and/or patch angioplasty) in 77 limbs (43%).
      The rates for technical and clinical success and complications in the entire
      group were 99%, 95%, and 4%, respectively. One patient died perioperatively
      (0.5%). Among the three periods, TransAtlantic Inter-Society Consensus lesion
      types were significantly more severe in patients in the first period (P < .05).
      Additionally, the complication rate was significantly higher and the mean
      hospital stay was significantly longer in the first period compared with the
      second and third periods (P < .05). Furthermore, between the first and third
      periods, the number of endovascular revascularization procedures done as primary
      and secondary procedures significantly increased from 15 to 84 (+460%) and from
      13 to 57 (+340%), whereas the number of open surgical procedures done as primary
      and secondary procedures decreased from 39 to 20 (-49%) and from 35 to 18 (-49%),
      respectively (P < .0001). The assisted primary patency rates in the third period
      were significantly higher than those in the first and second periods (P = .012);
      otherwise, the long-term outcomes among the three periods were not statistically
      different. Multivariate analysis revealed that, while controlling for other
      factors, the third period showed improvement in the primary patency (P = .032)
      and assisted primary patency (P = .051), and the bypass group showed improvement
      in the primary patency (P = .008). CONCLUSIONS: In our experience, open surgical
      procedures for the treatment of CLI have been largely replaced by angioplasty
      procedures without compromising outcomes. Angioplasty is a feasible, safe, and
      effective procedure and can be the procedure of choice for the primary and
      secondary treatment of CLI. Open surgical procedures can be reserved for lesions
      technically unsuitable for endovascular procedures and patients who do not
      demonstrate clinical improvement after angioplasty.

PMID- 16890856
TI  - Compromised bypass graft outcomes after minimal-incision vein harvest.
AB  - BACKGROUND: Minimal incision techniques for vein harvest may lessen wound
      complications after lower extremity revascularization, but long-term patency and
      limb salvage data are limited. METHODS: This retrospective case-control study
      used a computerized vascular registry set in an academic vascular surgical
      practice. All patients undergoing lower extremity revascularization using
      autogenous reversed great saphenous vein by a single vascular surgeon in a 10
      year period were reviewed. Harvest of great saphenous vein via long single
      incision (SI) in 133 patients was compared with minimal incisions with endoscopy
      (MIE) in 85, or MI without endoscopy in 106. The main outcome measures were
      primary and secondary graft patency by Kaplan-Meier life-table analysis and
      cumulative sum failure (CUSUM). Secondary outcomes of interest were limb salvage
      and wound complications. RESULTS: No differences were observed between MIE, MI,
      and SI patients for demographic data, risk factors, or primary indications,
      including claudication, rest pain, ischemic ulcer, and gangrene. Endoscopic vein
      harvest patients were significantly more likely than MI or SI to be women and
      more likely to use tobacco. Primary patency at 5 years was better after SI vein
      harvest (59%) than with either MI (33%, P = .004) or MIE (44%, P = .045)
      techniques, although both MI groups had a higher proportion of bypass grafts to
      the popliteal artery. Similarly, cumulative secondary patency was better after SI
      (66%) than with MI (47%, P = .045), but not MIE (58%, P = .45). Differences in
      limb salvage at 5 years in SI (73%) were not statistically superior to either MI
      (59%, P = .24) or MIE (58%, P = .13). No learning curve for MI or MIE vein grafts
      was evident by CUSUM for primary patency at 12 months. No differences in wound
      complication rates were observed for SI (9%), MI (10%), or MIE (6%) grafts (P =
      .54). CONCLUSIONS: Graft patency and limb salvage deteriorated during the time
      when MI or MIE techniques of great saphenous vein harvest were adopted. This
      observation raises concern about the advisability of limiting the extent of the
      incision at the potential cost of compromised outcomes without an obvious
      advantage in limiting wound complications.

PMID- 16890861
TI  - Risk factors for premature peripheral vascular disease: results for the National
      Health and Nutritional Survey, 1999-2002.
AB  - PURPOSE: Premature peripheral vascular disease (PVD), occurring <60 years of age,
      is associated with significant cardiovascular morbidity, limb loss, and death. We
      hypothesized that different risk factors predict the development of PVD in
      patients <60 years than in patients > or =60 years. METHODS: To address this
      question, we conducted a population-based observational study using the National
      Health and Nutritional Survey (NHANES) data set, which represents the
      noninstitutionalized civilian population in the United States. From 1999 to 2002,
      5083 participants were analyzed as part of the NHANES survey. PVD status was
      defined by an ankle-brachial index (ABI) of <0.9. Putative risk factors for the
      development of PVD were collected by physical examination, interview, and
      laboratory testing. Univariate and multivariate logistic regression analyses were
      used to evaluate interactions between age strata and the development of PVD.
      RESULTS: Premature PVD was found in 2.1% +/- 0.2% of the population <60 years,
      and PVD was found in 12.0% +/- 0.8% of the population > or =60 years. This
      corresponds to approximately 1.44 million people with premature PVD. Multivariate
      analysis determined coronary artery disease (odds ratio [OR] 2.90 vs 1.26, P =
      .083) and elevated serum fibrinogen (OR 1.07 vs 1.03, P = .034) were stronger
      predictors of PVD in subjects <60 years than in older subjects. Chronic renal
      insufficiency (OR 1.02 vs 1.16, P = .006) was more highly predictive of PVD in
      subjects >60 years. Other significant predictors, irrespective of age, in the
      multivariate model included hypertension (OR 1.99, P < .001), smoking (OR 2.22, P
      < .001), and serum homocysteine (OR 1.27, P = .067). CONCLUSIONS: Clinicians
      should be aware of the high risk of developing premature PVD in patients <60
      years with coexisting coronary artery disease or elevated plasma fibrinogen.
      Routine screening by ABI measurements in high-risk patients would enhance the
      detection of subclinical premature PVD and allow for secondary intervention.

PMID- 16890860
TI  - Peripheral arterial disease versus other localizations of vascular disease: the
      ATTEST study.
AB  - OBJECTIVE: Despite the increased cardiovascular morbidity and mortality risk of
      patients with peripheral arterial disease, previous worldwide studies have
      documented undertreatment of cardiovascular risk factors in such patients.
      METHOD: The ATTEST study was an observational cross-sectional epidemiologic
      study. Patients (n = 8475) were selected by 3020 general practitioners in France
      who were asked to include the first three patients with at least one site of
      proven atherothrombotic disease (peripheral arterial disease of the lower limbs
      for two patients and coronary artery disease or ischemic stroke for the third
      patient). We designed the ATTEST study to compare medical management of patients
      with peripheral arterial disease, including pharmacologic treatment,
      cardiovascular tests, and physician's assessment of future cardiovascular and
      amputation risks, with patients with coronary artery disease or ischemic stroke.
      RESULTS: Only 13% of the patients with peripheral arterial disease (n = 3811)
      received angiotensin converting enzyme inhibitors, statins, and antiplatelet
      agents vs 30% of the patients with coronary artery disease or ischemic stroke (n
      = 4664). This undertreatment of the population with peripheral arterial disease
      was associated with a too-optimistic physician's assessment of future
      cardiovascular risk: only 27% of the general practitioners predicted a 5-year
      cardiovascular risk >20%. Conversely, amputation risk prediction was greatly
      overestimated: only 44% of the practitioners predicted a 5-year amputation risk
      <5%. CONCLUSIONS: Patients with atherothrombotic disease recruited from primary
      care practices were not adequately tested and treated, especially the patients
      with peripheral arterial disease. To improve the medical management of patients
      with peripheral arterial disease, there is a need for epidemiologic and clinical
      education of physicians.

PMID- 16890863
TI  - Synergistic effect of Toll-like receptor 4 and CD14 polymorphisms on the total
      atherosclerosis burden in patients with peripheral arterial disease.
AB  - BACKGROUND: Genes involved in the regulation of immune responses, such as Toll
      like receptor 4 (TLR4) and CD14, show genetic variations with potential
      functional implications. Because atherosclerosis is an inflammatory process
      apparently modulated by chronic infections, we studied the effect of single
      nucleotide polymorphisms (SNPs) in TLR4 and CD14 on the extent of clinically
      relevant atherosclerosis in patients with peripheral arterial disease (PAD).
      METHODS: Using an in-house-developed polymerase chain reaction-based restriction
      length polymorphism assay, we determined the genotype, allele frequency, and
      carrier traits of the TLR4 +896 A>G and the CD14 -260 C>T SNPs in 607 white Dutch
      patients with PAD. The extent of clinically relevant atherosclerosis was
      determined on the basis of the number of vascular territories involved, ie,
      coronary, cerebral, aortic, and peripheral. RESULTS: A total of 55% of the
      patients had PAD only. Approximately one third of the patients had two and 11%
      had three vascular territories affected by clinically relevant atherosclerosis.
      The TLR4 +866 G allele frequency was 11%, and the CD14 -260 T allele frequency
      was approximately 74%. Among PAD patients, TLR4 +896 G allele carriership was
      univariantly associated with extensive (more than two vascular territories
      affected) atherosclerotic disease (odds ratio, 2.22; P = .020; chi(2) test),
      whereas CD14 -260 C>T carriership/homozygosity was not. Trend analysis showed
      that the TLR4 +866 G allele frequency increased with the number of vascular
      territories affected by clinically relevant atherosclerosis (P trend, .0074). In
      a multivariate logistic regression analysis including cardiovascular risk factors
      and TLR4 and CD14 SNPs, only the interaction variable "TLR4 +896 G allele
      carriership/CD14 -260 TT genotype" survived as an independent predictor of
      extensive atherosclerotic disease (P = .031; odds ratio, 4.2; 95% confidence
      interval, 1.1-15.4). CONCLUSIONS: The carrier trait TLR4 G allele/CD14 TT
      genotype, rather than each SNP individually, is associated with the extent of
      clinically relevant atherosclerotic disease. Considering the importance of immune
      responses in atherogenesis and the genetic variation of immune regulatory genes,
      our data provide an explanation for interindividual differences in susceptibility
      to atherosclerosis and demonstrate the need to take a wider approach in analyzing
      relevant carrier traits instead of individual polymorphisms in relation to
      atherosclerosis.

PMID- 16890864
TI  - Prevalence of peripheral arterial disease and its association with smoking in a
      population-based study in Beijing, China.
AB  - OBJECTIVE: Although the prevalence of peripheral arterial disease (PAD) and its
      association with smoking in Western populations has been extensively studied,
      little information is available in China. The objective of this study was to
      determine the age-standardized prevalence of PAD and examine the relationship
      between smoking, quitting, and PAD in elderly Chinese. METHODS: We conducted a
      population-based cross-sectional study in an urban Beijing sample of 2334
      subjects aged > or =60 years (943 men and 1391 women) in 2001 to 2002. PAD was
      assessed by symptoms of intermittent claudication (IC) as measured by the
      WHO/Rose questionnaire and an ankle-arm systolic blood pressure index (AAI) of
      <0.90. RESULTS: The prevalence of PAD defined by IC was 11.3% (men, 8.0%; women,
      13.6%); 15.3% (men, 11.7%; women, 17.7%) by AAI, and 19.8% (men, 14.7%; women,
      23.2%) by both criteria. After adjusting for age, gender, marital status,
      education, alcohol drinking, exercise, body mass index, and histories of
      hypertension and diabetes mellitus, the odds ratios and 95% confidence intervals
      of PAD for current smokers vs never smokers were 1.54 (1.12 to 2.11) and 1.28
      (0.91 to 1.79) for former smokers (stopped smoking for at least 2 years). There
      was a dose-response relation between the number of cigarettes smoked and
      increasing risk of PAD. Quitting for > or =10 years nearly eliminated excess risk
      associated with smoking. CONCLUSIONS: PAD is common in elderly Chinese and the
      prevalence is higher in women than in men. About 40% of PAD patients were
      asymptomatic and unaware of their condition. Cigarette smoking is a major risk
      factor for PAD, and smoking cessation substantially reduces the risk.

PMID- 16890865
TI  - InterGard silver bifurcated graft: features and results of a multicenter clinical
      study.
AB  - OBJECTIVES: Recent research in vascular surgery has focused on development of
      infection-resistant prosthetic grafts. This article describes the results of a
      multicenter study to evaluate safety, patency, and infection rates after
      implantation of the InterGard Silver bifurcated polyester graft coated with
      collagen and silver. METHODS: Between October 2000 and February 2002, 289
      consecutive patients were implanted with a collagen and silver acetate-coated
      polyester bifurcated graft at 16 French vascular surgery centers. Mean patient
      age was 65.3 +/- 10.9 years. The indication for prosthetic bypass was aortic
      aneurysm in 160 patients (55.4%) and symptomatic aortoiliac occlusive disease in
      129 (44.6%). All but four patients received prophylactic antibiotic therapy.
      Patency was assessed at 30 days, 1 year, 2 years, and 3 years, primarily by
      duplex scan. RESULTS: Two patients (0.7%) died during the first 30 days. Median
      duration of hospitalization was 11 days. The Kaplan-Meier survival rate at 3
      years was 85.7% +/- 4.1%. Primary and secondary patency rates at 3 years were
      94.9% +/- 2.6% and 97.5% +/- 1.8%. Thrombectomy was performed successfully in
      seven patients, and a major amputation was required in two patients with patent
      grafts. Postoperative complications, including 39 nosocomial infections, were
      observed in 107 patients (37.0%). Eleven patients presented with 12 wound
      infections that were classified Szilagyi grade I in eight cases, grade II in two
      cases, and grade III with graft infection in two cases (0.7%). Among the 149
      patients undergoing aortofemoral bypass, eight (5.4%) presented with wound
      infection, including two graft infections (1.3%). Among the 140 patients
      undergoing aortoiliac bypass, only three patients (2.1%) presented wound
      infection and none with graft infection (P = .15). Three (16.7%) of 18 patients
      who had undergone previous femoral revascularization and eight (3%) of 271
      patients without previous femoral revascularization presented with wound
      infection. This difference was statistically significant (P = .03), with a
      relative risk of 5.6 (95% confidence interval [CI], 1.6 to 19.5). Five (11.9%) of
      42 diabetic patients and six (2.4%) of 247 nondiabetic patients presented with
      wound infection. This difference was also statistically significant (P = .01),
      with a relative risk of 3.4 (95% CI, 1.7 to 6.9). Lymphorrhea or lymphocele
      developed in the groin of 25 patients (8.6%) with negative culture. CONCLUSION:
      This multicenter prospective study shows that the InterGard Silver graft is safe
      with no side effects. The primary patency rate was excellent, and the graft
      infection rate was low, despite a high incidence of nosocomial infections.

PMID- 16890866
TI  - Clinical outcomes after closed, staged, and open forefoot amputations.
AB  - BACKGROUND: Surgical approaches for forefoot osteomyelitis include amputation
      with immediate wound closure or resection followed by either staged re-resection
      and wound closure or local care of the open wound for secondary healing. This
      study evaluated the effectiveness of closed, staged, and open forefoot
      amputations in preventing major leg amputation and identified those variables
      that are associated with successful limb preservation. METHODS: From July 2002 to
      June 2004, 208 patients with forefoot osteomyelitis or gangrene underwent minor
      amputation according to a standard treatment algorithm. Wounds with limited
      cellulitis underwent immediate wound closure (CLOSED), wounds with marginally
      viable soft tissue underwent open amputation followed by wound closure at 2 to 7
      days (STAGED), and wounds with tenosynovitis or extensive necrosis underwent
      debridement with no attempt at wound closure (OPEN). Patient demographics, need
      for further operative interventions, time to complete healing, and progression to
      major amputation were recorded. RESULTS: With four subjects lost to follow-up,
      204 patients (98%) (94 CLOSED, 56 STAGED, and 54 OPEN) were monitored to complete
      healing, major amputation, or death. OPEN amputations had a significantly reduced
      initial healing rate (37%, P < .001) and a frequent need for repeat operative
      intervention (43%), although successful limb salvage was ultimately achieved in
      70% of the cases. Initial healing in the CLOSED and STAGED amputation groups was
      similar (71% and 78%, respectively), leading to excellent early limb salvage (86%
      and 91%). The median time to healing for closed, staged, and open amputations was
      1.2, 1.6, and 4.6 months, respectively (P < .001). Follow-up evaluation
      demonstrated the initial improvements in limb salvage with the CLOSED and STAGED
      groups were lost, resulting in similar amputation rates among the three groups of
      30% to 35% over 36 months. CONCLUSIONS: Although open amputation of extensive
      forefoot infections frequently requires repeat operative interventions and a
      prolonged time to complete healing, this approach provides limb salvage rates
      approaching those observed for less invasive infections amenable to immediate
      closure. Staged closure offers an improved time to healing without negatively
      impacting the risk of major limb amputation. Independent of their initial
      operative approach, these patients frequently progress to early leg amputation.

PMID- 16890868
TI  - Forearm cephalic vein cross-sectional area changes at incremental congestion
      pressures: towards a standardized and reproducible vein mapping protocol.
AB  - OBJECTIVES: Duplex ultrasonography assessment of superficial forearm veins is
      frequently used before a hemodialysis arteriovenous fistula (AVF) is created.
      There is, however, no standardized preoperative duplex ultrasonography protocol.
      This study assessed B-mode image analysis reproducibility and reproducibility of
      repeated forearm superficial venous diameter measurements on different days at
      different venous congestion pressures (VCPs). METHODS: Diameters were determined
      using B-mode ultrasonography in 10 healthy male volunteers on days 1 and 14 at
      incremental VCP values (10 to 80 mm Hg). Intra- and interobserver agreement was
      assessed for B-mode image analysis by calculating interclass correlation
      coefficients (ICC). Reproducibility of repeated diameter measurements (maximum
      and minimum diameter at days 1 and 14), cross-sectional area size increase, and
      shape change due to incremental VCPs were determined by calculating ICC values.
      RESULTS: Analysis of intraobserver agreement of B-mode image interpretation
      yielded ICC values of 0.97 (95% confidence interval [CI], 0.94 to 0.99) and 0.97
      (95% CI, 0.96 to 0.99) for determination of maximum and minimum diameters,
      respectively. Interobserver agreement analysis yielded ICC values of 0.95 (95%
      CI, 0.92 to 0.97) and 0.96 (95% CI, 0.96 to 0.99) for determination of maximum
      and minimum diameters, respectively. Reproducibility of repeated diameter
      measurements on days 1 and 14 improved substantially at incremental VCP values,
      with best reproducibility at VCPs >40 mm Hg. Repeated determination of cross
      sectional area size increase and shape change due to VCP increase from 10 to 80
      mm Hg yielded ICC values of 0.49 (95% CI, 0.19 to 1.00) and 0.09 (95% CI, 0.00 to
      0.92), respectively. Maximum and minimum diameters as well as cross-sectional
      area size increased significantly (P < .01) due to VCP increase during both
      sessions. Cross-sectional area shape changed significantly (P < .01) due to VCP
      increase during both sessions. CONCLUSIONS: Diameter measurements on B-mode
      images are largely observer independent. Superficial venous cross-sectional area
      shape is noncircular, and cross-sectional area size depends on VCP. Both maximum
      and minimum venous diameters should be determined at VCPs >40 mm Hg to attain the
      best reproducibility. Further studies are needed to determine whether a
      standardized preoperative vein mapping protocol can reduce AVF nonmaturation
      rates.

PMID- 16890869
TI  - Mid-term recurrence rate of incompetent perforating veins after combined
      superficial vein surgery and subfascial endoscopic perforating vein surgery.
AB  - BACKGROUND: This study investigated the mid-term (mean, 3.7 years) clinical
      results and the results of duplex Doppler sonographic examinations of subfascial
      endoscopic perforating vein surgery (SEPS) in patients with mild to severe
      chronic venous insufficiency (clinical class 2-6) and assessed the factors
      associated with the recurrence of insufficient perforating veins (IPVs). METHODS:
      Eighty patients with mild to severe chronic venous insufficiency undergoing SEPS
      were evaluated, and duplex findings, as well as clinical severity and disability
      scores before and after the operation, were compared. Patients with prior deep
      vein thrombosis (<6 months) or prior SEPS were excluded from this study. RESULTS:
      There were 27 men and 53 women with a median age of 59.8 years (range, 34.3-80.0
      years). The distribution of clinical classes (CEAP) was as follows: class 2,
      13.1% (12 limbs); class 3, 22.8% (21 limbs); class 4, 19.6% (18 limbs); class 5,
      21.7% (20 limbs); and class 6, 22.8% (21 limbs). The etiology of venous
      insufficiency was primary valvular incompetence in 83 limbs (90.2%) and secondary
      disease in 9 limbs (9.8%). Concomitant superficial vein surgery was performed in
      89 limbs (95.7%). Twenty (95%) leg ulcers healed spontaneously within 12 weeks
      after operation, whereas one patient required additional split-thickness skin
      grafting. Eighteen patients had previous surgery of the great and/or short
      saphenous vein before SEPS. During a mean follow-up of 3.7 years, recurrence of
      22 IPVs was observed in 20 (21.7%) of 92 limbs, and recurrent leg ulcers were
      observed in 2 (9.5%) of 21 limbs. We performed univariate and multivariate
      analyses to predict factors influencing the recurrence of IPVs (recurrent
      superficial varicosis, secondary disease, active or healed leg ulcer [C5/6],
      compression treatment, and previous operation). On multivariate analysis,
      previous surgery (P = .014) was identified as the only significant factor for the
      recurrence of IPVs. CONCLUSIONS: SEPS is a safe and highly effective treatment
      for IPVs. Within a median follow-up period of 3.7 years, only 2 of 21 venous
      ulcers recurred, both in patients with secondary disease. Nevertheless, we
      observed recurrence of IPVs in 21.7% of the operated limbs. On multivariate
      analysis, patients who had undergone previous surgery were found to have a
      significantly higher rate of recurrence.

PMID- 16890870
TI  - Angiotensin II induces histomorphologic features of unstable plaque in a murine
      model of accelerated atherosclerosis.
AB  - BACKGROUND: We explored the role of angiotensin II in determining the
      histomorphometric features of plaque stability in apolipoprotein E-deficient mice
      submitted to ligation of the carotid artery. METHODS: Six-month-old
      apolipoprotein E-deficient mice underwent ligation of the common left carotid
      artery and were immediately assigned to receive either angiotensin II (1.4 mg .
      kg(-1) . d(-1) subcutaneously) or vehicle (phosphate-buffered saline; control)
      via a subcutaneous osmotic minipump for 4 weeks. RESULTS: Ligated arteries from
      control animals developed intimal lesions composed of macrophage foam cell
      plaques, which accumulated adjacent to the internal elastic lamina and were
      surrounded by a fibromuscular layer. Angiotensin II-treated mice had a greater
      intimal area (threefold), which was accompanied by a fivefold increase in the
      foam cell area. Lesions from angiotensin II-treated mice also displayed complex
      morphology characterized by intralesional neovasculature and hemorrhage. The
      content of active matrix metalloproteinase 2, mainly colocalized with macrophage
      foam cells, and the production of the inflammatory mediators monocyte
      chemoattractant protein 1 and vascular cell adhesion molecule 1 were also
      increased by angiotensin II treatment. Although angiotensin II induced vessel
      expansion and lumen loss to a similar extent, only vessel enlargement correlated
      with intimal area. CONCLUSIONS: Taken together, this study's results support a
      role of angiotensin II in plaque vulnerability by promoting intraplaque
      neovascularization/hemorrhage, inflammation, and expansive remodeling.

PMID- 16890871
TI  - Rapid dilation of the abdominal aorta during infusion of angiotensin II detected
      by noninvasive high-frequency ultrasonography.
AB  - BACKGROUND: Infusion of angiotensin II (AngII) via subcutaneous osmotic pumps
      into mice promotes the development of abdominal aortic aneurysms (AAAs). These
      AngII-induced AAAs develop via a complex process in which there is a transmedial
      break, lumen dilation, thrombus formation, inflammation involving cells of both
      the innate and acquired immune systems, and remodeling. The recent development of
      a high-frequency ultrasound machine has permitted the noninvasive detection of
      murine abdominal aortas. We assessed the ability of a Visualsonics Vevo 660 high
      resolution imaging system to detect AAAs and sequentially quantify the aortic
      luminal diameter. This system had 100% accuracy in detecting AngII-induced AAAs
      in vivo, with intrauser and interuser variation coefficients of less than 10% for
      quantification of the aortic lumen diameter. METHODS: Male apolipoprotein E
      (apoE)(-/-) mice were infused subcutaneously with either saline or AngII and were
      monitored with this ultrasonic system to define the temporal changes in aortic
      lumen diameter. Aortic luminal diameters were measured in the aneurysm
      susceptible region of the suprarenal aorta. For internal controls, abdominal
      aortic diameters were measured at the level of the left renal branch, because
      this landmark region did not dilate during AngII infusion. RESULTS: Luminal
      diameters of the suprarenal aorta did not change significantly in saline-infused
      mice over 28 days of measurement (P = .71). In contrast, AngII infusion led to
      rapid dilation of suprarenal aortas during the initial 7 days of infusion (0.071
      mm/d; P = .0037 for the change in the initial expansion rate). Further luminal
      diameter expansions occurred for the remaining 21 days of observation at a more
      modest rate (0.023 mm/d; P = .0001 for continued expansion after day 7). Within
      the initial 14 days of AngII infusion, some apoE(-/-) mice died as a result of
      rupture of the aorta in the suprarenal region. We had previously assumed that
      aortic dilation and rupture occurred simultaneously. However, in the AngII
      infused mice that succumbed to aortic rupture, luminal diameters increased
      several days before death. CONCLUSIONS: High-frequency ultrasonography
      demonstrated that suprarenal aortic expansion occurs rapidly after the initiation
      of AngII infusion into apoE(-/-) mice.

PMID- 16890872
TI  - Sustained-release vancomycin sheet may help to prevent prosthetic graft
      methicillin-resistant Staphylococcus aureus infection.
AB  - OBJECTIVE: The purpose of this study was to evaluate the effectiveness of a
      sustained-release sheet with vancomycin (VCM) to prevent prosthetic graft
      infection. METHODS: VCM was incorporated into a poly-L-lactide-co-caprolactone
      (PLCA) sheet (VCM-PLCA). The release profile of VCM from the VCM-PLCA sheet and
      the tissue concentration of VCM released in vivo were examined. To assess the
      antibacterial effect of the VCM-PLCA sheet, a sterile Dacron sheet was implanted
      into 96 male mice (C57BL/6), who were randomly divided into four groups of 24
      each and treated as follows: no treatment (group A, control group), a local bolus
      injection of an aqueous solution of VCM (group B), a plain PLCA sheet (group C),
      and a VCM-PLCA sheet (group D). After the treatment, methicillin-resistant
      Staphylococcus aureus (MRSA) (1 x 10(6) colony forming units) was inoculated onto
      the Dacron graft surface. The Dacron grafts were retrieved on days 3, 7, 10, and
      14 after the implantation, and the number of MRSA in the Dacron grafts was
      counted. RESULTS: VCM was slowly released from the VCM-PLCA sheet over 2 weeks in
      vivo, and the mean in vivo concentrations of VCM in the tissue around a VCM-PLCA
      sheet were 7.95, 26.39, 13.87, 12.51, 8.36, and 10.33 mug/mL (the minimum
      inhibitory concentration of VCM against MRSA is 2.0 mug/ml), at 1, 2, 5, 7, 10,
      and 14 days after the implantation, respectively. MRSA colonization on the
      cultivated agar plates was detected in all samples from groups A, B, and C at any
      postoperative time points. In contrast, some samples were negative for bacterial
      cultures in group D (2, 3, 1, and 2 samples out of 6 samples each on days 3, 7,
      10, and 14 after the implantation, respectively). At all time points, the number
      of MRSA bacteria in the implanted Dacron graft in group D was by far the lowest
      (P < .01 at each time point). CONCLUSIONS: The sustained-release sheet with VCM
      appears to be effective for the reduction of subcutaneous prosthetic graft
      infection.

PMID- 16890873
TI  - Iodinated contrast induced renal vasoconstriction is due in part to the
      downregulation of renal cortical and medullary nitric oxide synthesis.
AB  - OBJECTIVES: The loss of renal function continues to be a frequent complication of
      the iodinated contrast agents used to perform diagnostic angiography and
      endovascular procedures. This study examined the hypothesis that contrast-induced
      renal injury is partly due to a decrease in cortical and medullary microvascular
      blood flow after the downregulation of endogenous renal cortical and medullary
      nitric oxide (NO) synthesis. METHODS: Anesthetized male Sprague-Dawley rats (300
      g) had microdialysis probes or laser Doppler fibers inserted into the renal
      cortex to a depth of 2 mm and into the renal medulla to a depth of 4 mm. Laser
      Doppler blood flow was continuously monitored, and the microdialysis probes were
      connected to a syringe pump and perfused in vivo at 3 muL/min with lactated
      Ringer's solution. Dialysate fluid was collected at time zero (basal) and 60
      minutes after infusion of either saline or Conray 400 (6 mL/kg). Both groups were
      treated with saline carrier, N(omega)-nitro-L-arginine methyl ester hydrochloride
      (L-NAME, 30 mg/kg), L-arginine (400 mg/kg), or superoxide dismutase (10,000
      U/kg), an oxygen-derived free radical scavenger. Dialysate was analyzed for total
      NO and eicosanoid synthesis. The renal cortex and medulla were analyzed for
      inducible NO synthase (iNOS), cyclooxygenase-2 (COX2), prostacyclin synthase, and
      prostaglandin E(2) (PGE(2)) synthase content by Western blot analysis. RESULTS:
      Conray caused a marked decrease in cortical and medullary blood flow with a
      concomitant decrease in endogenous cortical NO, PGE(2), and medullary NO
      synthesis. The addition of L-NAME to the Conray further decreased cortical and
      medullary blood flow and NO synthesis, which were restored toward control by L
      arginine. Neither L-NAME nor L-arginine (added to the Conray) altered cortical or
      medullary eicosanoids release. Medullary PGE(2) synthesis decreased when
      superoxide dismutase was added to the Conray treatment, suggesting that oxygen
      derived free radicals had a protective role in maintaining endogenous medullary
      PGE(2) synthesis after Conray treatment. Conray did not significantly alter iNOS,
      COX-2, prostacyclin synthase, or PGE(2) synthase content. CONCLUSIONS: These
      findings suggest that the downregulation of renal cortical and medullary NO
      synthesis contributes to the contrast-induced loss of renal cortical and
      medullary microvascular blood flow. Preservation of normal levels of renal
      cortical and medullary NO synthesis may help prevent or lessen contrast-induced
      renal vasoconstriction and lessen contrast-induced renal injury found after
      diagnostic and therapeutic endovascular procedures.

PMID- 16890875
TI  - Vascular reconstruction using deep vein for limb length discrepancy in a child.
AB  - Iatrogenic vascular injuries can result in claudication and limb length
      discrepancy in growing children. Traditional reconstruction has been performed
      with great saphenous vein as a conduit. We report the case of a 7-year-old boy
      with a symptomatic limb length discrepancy and vascular reconstruction using
      femoropopliteal vein. The use of deep vein as an autogenous conduit may
      facilitate reconstruction of iliofemoral arteries in preadolescent children,
      providing an excellent size match and an efficacious means of restoring normal
      blood flow.

PMID- 16890876
TI  - Tetraplegia after elective abdominal aortic aneurysm repair.
AB  - Spinal cord ischemia after elective infrarenal aortic aneurysm repair is
      extremely rare, and documented cases that are described are of paraplegia. This
      case of tetraplegia occurred in a 64-year-old man with disabling claudication
      after an aortobifemoral graft repair for occlusive disease associated with a 5-cm
      infrarenal aneurysm. Magnetic resonance imaging supported lower cervical spinal
      cord ischemia, an unusual area for ischemia during aortic clamping since this
      area is usually most resistant. Because the lower thoracic and upper lumbar
      region, typically T8, is more susceptible to ischemia due to the variable
      collateral spinal cord circulation, the level of clamping was unlikely to be
      responsible. Other causes are considered. It was likely to be multifactorial and
      illustrates the need for great attention to detail in perioperative management
      and patient consent.

PMID- 16890877
TI  - The hybrid elephant trunk procedure: a single-stage repair of an ascending, arch,
      and descending thoracic aortic aneurysm.
AB  - Surgical repair of extensive aortic aneurysms requires a two-stage approach. We
      present the case of a single-stage repair using a hybrid procedure. This case
      demonstrates the technical feasibility of repairing properly selected extensive
      aortic aneurysms in a single procedure.

PMID- 16890874
TI  - Functional and cytoarchitectural spinal cord protection by ATL-146e after
      ischemia/reperfusion is mediated by adenosine receptor agonism.
AB  - BACKGROUND: ATL-146e protects the spinal cord from ischemia/reperfusion injury,
      presumably via adenosine A(2A) receptor activation, but this relationship remains
      unproven. We hypothesized that spinal cord functional and cytoarchitectural
      preservation from ATL-146e would be lost with simultaneous administration of the
      specific adenosine A(2A) antagonist ZM241385 (ZM), thus proving that adenosine
      A(2A) receptor activation is responsible for the protective effects of this
      compound. METHODS: New Zealand White rabbits underwent 45 minutes of infrarenal
      aortic cross-clamping. Groups (n = 10) included sham, ischemia, ischemia plus ATL
      146e (ATL-146E), ischemia plus ZM, or ischemia with both compounds (agonist
      antagonist). Tarlov scores were recorded every 12 hours. After 48 hours, the
      spinal cord was fixed for histology and microtubule-associated protein 2
      immunohistochemistry. RESULTS: Tarlov scores at 48 hours were significantly
      better in the sham and ATL-146E groups (5.0 and 3.9, respectively) compared with
      the other three groups (all < or =1.3; P < .001). On hematoxylin and eosin,
      neuronal viability was higher in the sham, ATL-146E, and agonist-antagonist
      groups compared with the control and ZM groups (P < .05). Microtubule-associated
      protein 2 expression was preserved in the sham and ATL-146E groups but was lost
      in the ATL + ZM, ZM241385, and control groups. CONCLUSIONS: ATL-146e preserves
      the spinal cord in terms of both cytoarchitecture and function after reperfusion
      of the ischemic spinal cord, but this preservation is not completely blocked by
      competitive adenosine A(2A) receptor antagonism. Although ATL-146e does seem to
      partially function through activation of the adenosine A(2A) receptor, the
      neuroprotective mechanism may not be limited to this particular receptor.

PMID- 16890878
TI  - Aortoenteric fistula as a late complication of thrombolysis and bare metal
      stenting for perioperative occlusion of aortofemoral bypass.
AB  - We previously described the case of a 47-year-old man who experienced
      perioperative graft occlusion after infrarenal aortic endarterectomy and
      aortobifemoral expanded polytetrafluoroethylene bypass graft for occlusive
      disease. The patient was treated with local graft thrombolysis and stenting of an
      intimal flap at the level of the endarterectomized aorta next to the aortic
      anastomosis. An urgent laparotomy performed 6 years later showed aortic wall
      perforation by the stent with a large aortoenteric fistula. Surgical treatment
      included removal of the stent and the aortobifemoral graft, bowel repair, and
      extra-anatomic lower-limb revascularization by axillofemoral and cross-femoral
      bypass grafting. The patient was discharged 12 days later with no early
      complications. Although local thrombolysis and stenting may be a technically
      feasible technique instead of reoperation in early aortofemoral graft thrombosis,
      long-term results of this procedure may be affected by perigraft hematoma due to
      perioperative thrombolysis, increased risk of infection due to the prolonged
      intragraft cannulation, and risk of stent-related aortic injury, especially if an
      endarterectomy has been performed. All these issues may increase the risk of late
      aortoenteric fistula. More experience with hybrid, open/endovascular procedures,
      and more contemporary stent-based devices is needed to assess the efficacy and
      safety of this alternative treatment.

PMID- 16890879
TI  - Delayed deformation of self-expanding stents after carotid artery stenting for
      postendarterectomy restenoses.
AB  - Carotid artery stenting has become an acceptable alternative for treating
      patients with severe atherosclerotic lesions, particularly those with significant
      surgical risks, such as recurrent stenosis after endarterectomy. Stent
      deformation, a phenomenon primarily associated with balloon-expandable stents, is
      largely avoided by exclusively using self-expanding stents in treating carotid
      artery stenosis. Nonetheless, we herein report two patients who presented with
      delayed Wallstent deformation after carotid artery stenting for
      postendarterectomy restenosis. Our cases highlight the need for caution because
      delayed deformation of self-expanding stents can occur, particularly during
      treatment of patients with postendarterectomy stenosis. Furthermore, poststent
      surveillance is imperative in identifying patients with severe restenosis after
      carotid artery stenting who need reintervention.

PMID- 16890880
TI  - Congenital absence of the inferior vena cava: a rare risk factor for idiopathic
      deep-vein thrombosis.

PMID- 16890881
TI  - Endoscopic vein harvest in peripheral vascular surgery.

PMID- 16890882
TI  - Statins for the prevention of perioperative cardiovascular complications in
      vascular surgery.
AB  - Perioperative cardiovascular complications in vascular surgery remain a
      significant problem despite recent advancements in perioperative care. This
      clinical update summarizes the results of recent studies on the effectiveness and
      safety of perioperative statin use for the prevention of these perioperative
      cardiovascular complications. Five studies in patients undergoing major
      noncardiac vascular surgery and two studies in patients undergoing carotid
      endarterectomy are described. All studies reported a significant reduction in
      perioperative cardiovascular events in statin users compared with nonusers. The
      safety of perioperative statin use has not yet been fully elaborated, although
      current evidence suggests there is no extra risk from statin-induced side effects
      in the perioperative period.

PMID- 16890883
TI  - The EXercise versus Angioplasty in Claudication Trial (EXACT): reasons for
      recruitment failure and the implications for research into and treatment of
      intermittent claudication.

PMID- 16890885
TI  - Regarding "Endovascular management of iliac artery occlusions: extending
      treatment to TASC C and D lesions".

PMID- 16890886
TI  - Pathological muscle activation patterns in patients with massive rotator cuff
      tears, with and without subacromial anaesthetics.
AB  - A mechanical deficit due to a massive rotator cuff tear is generally concurrent
      to a pain-induced decrease of maximum arm elevation and peak elevation torque.
      The purpose of this study was to measure shoulder muscle coordination in patients
      with massive cuff tears, including the effect of subacromial pain suppression.
      Ten patients, with MRI-proven cuff tears, performed an isometric force task in
      which they were asked to exert a force in 24 equidistant intervals in a plane
      perpendicular to the humerus. By means of bi-polar surface electromyography (EMG)
      the direction of the maximal muscle activation or principal action of six
      muscles, as well as the external force, were identified prior to, and after
      subacromial pain suppression. Subacromial lidocaine injection led to a
      significant reduction of pain and a significant increase in exerted arm force.
      Prior to the pain suppression, we observed an activation pattern of the arm
      adductors (pectoralis major pars clavicularis and/or latissimus dorsi and/or
      teres major) during abduction force delivery in eight patients. In these eight
      patients, adductor activation was different from the normal adductor activation
      pattern. Five out of these eight restored this aberrant activity (partly) in one
      or more adductor muscles after subacromial lidocaine injection. Absence of
      glenoid directed forces of the supraspinate muscle and compensation for the lost
      supraspinate abduction torque by the deltoideus leads to destabilizating forces
      in the glenohumeral joint, with subsequent upward translation of the humeral head
      and pain. In order to reduce the superior translation force, arm adductors will
      be co-activated at the cost of arm force and abduction torque. Pain seems to be
      the key factor in this (avoidance) mechanism, explaining the observed limitations
      in arm force and limitations in maximum arm elevation in patients suffering
      subacromial pathologies. Masking this pain may further deteriorate the
      subacromial tissues as a result of proximal migration of the humeral head and
      subsequent impingement of subacromial tissues.

PMID- 16890888
TI  - The Ro 60 kDa autoantigen comes into focus: interpreting epitope mapping
      experiments on the basis of structure.
AB  - A conserved RNA-binding protein, the Ro 60 kDa (Ro60) autoantigen, is a major
      target of autoantibodies in patients suffering from the rheumatic diseases
      Sjogren's syndrome, systemic lupus erythematosus, subacute cutaneous lupus
      erythematosus and neonatal lupus erythematosus. In both mice and certain
      bacteria, Ro60 is important for cell survival following ultraviolet irradiation.
      Although the function of Ro60 was mysterious for many years, recent experiments
      have demonstrated that this protein binds misfolded noncoding RNAs in vertebrate
      cells and likely functions in a pathway by which defective RNAs are recognized
      and targeted for degradation. Recent structural studies have revealed that Ro60
      is shaped like a doughnut with an inner hole. Noncoding RNAs called Y RNAs bind
      on the outer surface of the ring, while the single-stranded ends of misfolded
      RNAs likely bind within the hole. Comparison of the Ro60 structure with the
      results of epitope-mapping studies reveals that many of the currently identified
      epitopes recognized by patient sera overlap regions of Ro60 that function in RNA
      binding. Moreover, in some patients with anti-Ro60 antibodies, the initial
      antigenic epitope corresponds to a loop involved in binding single-stranded RNA
      in the central cavity.

PMID- 16890889
TI  - T cell-mediated activation and regulation of anti-chromatin B cells.
AB  - We have taken an immunoglobulin transgenic approach to study how self-reactive B
      cells are held in check in healthy mice and what parameters contribute to their
      activation in autoimmunity. Using this strategy, we have documented that a
      population of anti-chromatin B cells migrate to the periphery. In a healthy
      background, these cells have a reduced lifespan, appear developmentally arrested,
      and localize primarily to the T/B cell interface in the spleen. Importantly, they
      are capable of differentiating into antibody-forming cells when provided with T
      cell help. T(H)1 and T(H)2 cells induce IgG2a and IgG1 autoantibodies,
      respectively. In the context of the autoimmune-prone lpr/lpr or gld/gld
      mutations, these autoreactive B cells populate the B cell follicle, and this is
      dependent upon CD4 T cells. However, after 10 weeks of age serum autoantibodies
      are produced. We hypothesize that control of autoantibody production in young
      autoimmune-prone mice is regulated by the counterbalancing influence of
      regulatory T cells. We show that while autoantibody production is blocked in the
      context of regulatory T cells, early events characterizing a productive T cell-B
      cell interaction are not disturbed, with the notable exceptions of T(H) ICOS
      levels and IFN-gamma and IL-10 production.

PMID- 16890890
TI  - Regulation of Fli1 gene expression and lupus.
AB  - Ets transcription factors function throughout development in such varied
      processes as cellular proliferation, apoptosis, differentiation and migration.
      Many have been implicated to play important roles in hematopoiesis,
      vasculogenesis/angiogenesis and myogenesis. Fli1 is an Ets family member that is
      essential for development and increasing evidence suggests modulating Fli1 gene
      expression impacts lymphocyte function and is important in the autoimmune disease
      lupus. Presently, it is unknown how Fli1 gene expression is controlled in
      lymphocytes. Identifying upstream regulators of Fli1 in lymphocytes will be
      critical for understanding lymphocyte development and the consequences of
      dysregulation and may be of value in developing future treatments for lupus.

PMID- 16890891
TI  - Urinary biomarkers in lupus nephritis.
AB  - There has long been a need for biomarkers of disease activity in lupus nephritis
      (LN). Such markers ideally would be capable of detecting early sub-clinical
      disease and could be used to gauge response to therapy thus obviating the need
      for serial renal biopsies. Since urine can be readily obtained it lends itself as
      an obvious biological sample. Much of the focus has been on the measurement of
      urinary chemokines and cytokines in patients with LN. Elevations in urinary IL-6
      and IL-10 had initially been reported to be associated with disease activity in
      LN but these markers have proven to be less reliable in larger studies. We and
      others have recently reported that MCP-1, a key chemokine involved in monocyte
      chemotaxis can be consistently found at high levels in the urine of patients with
      active LN. Moreover urinary MCP-1 levels decline with treatment of nephritis. In
      contrast urinary IL-8, a chemokine involved primarily in neutrophil chemotaxis is
      not a good predictor of disease activity in LN. Further longitudinal studies with
      larger numbers of patients are needed to determine the utility of urinary
      biomarkers such as MCP-1 which may act as surrogates of ongoing inflammation in
      LN.

PMID- 16890892
TI  - The genetic basis of autoantibody production.
AB  - Many autoimmune diseases are characterized by autoantibody subsets that are
      associated with specific clinical manifestations. The primary genetic
      associations of these autoantibodies are with MHC genes, most specifically HLA
      class II, which in many instances better explain the HLA association of the
      disease per se. It is noteworthy that certain genes and haplotypes, notably HLA
      DRB1*0301, DQA1*0501, DQB1*0201 in Caucasians and DRB1*0405, DQA1*03, DQB1*0401
      in Asians, as well as PTPN22, seem to be associated with a variety of autoimmune
      diseases. On the other hand, others are more disease specific (HLA-DRB1*11 for
      systemic sclerosis and HLA-DRB1 alleles encoding the "shared epitope" in RA) as
      well as non MHC genes, such as FcyRIIa and IIIa in SLE, the beta2 glycoprotein I
      gene in the aPL syndrome, and the TSHR gene in Graves' disease). Autoantibody
      responses also are influenced by the presence of specific MHC and non-MHC genes
      which may not be associated with the disease per se. These novel associations
      offer new clues not only to pathogenesis but also to potential therapeutic
      targets.

PMID- 16890894
TI  - Role of B-1a cells in autoimmunity.
AB  - B-1a cells are distinguished from conventional B cells (B2) by their
      developmental origin, their surface marker expression and their functions. They
      were originally identified as a B cell subset of fetal origin that expresses the
      pan-T cell surface glycoprotein, CD5. B-1a cells also differ from B2 by the
      expression levels of several surface markers, including IgM, IgD, CD43 and B220
      [R. Berland, H.H. Wortis, Origins and functions of B-1 cells with notes on the
      role of CD5. Ann Rev Immunol, 20 (2002) 253-300.]. The majority of B-1a cells are
      located in peritoneal and pleural cavities. Compared to B2 cells, B-1a are long
      lived, non-circulating, with reduced BCR diversity and affinity [A.B. Kantor,
      C.E. Merrill, L.A. Herzenberg, J.L. Hillson, An unbiased analysis of V-H-D-J(H)
      sequences from B-1a, B-1b, and conventional B cells. J Immunol, 158 (1997) 1175
      1186.]. B-1a cells are largely responsible for the production of circulating IgM
      referred to as natural antibodies. These low affinity antibodies are polyreactive
      and constitute as such a first line of defense against bacterial pathogens [M.C.
      Carroll, A.P. Prodeus, Linkages of innate and adaptive immunity. Curr Opin
      Immunol, 10 (1998) 36-40.]. This polyreactivity also results into the recognition
      of autoantigens, which serves in the clearance of apoptosis products. The weak
      autoreactivity of the B-1a cells has been postulated to play a role in autoimmune
      pathogenesis. In addition, other characteristics, such as the production of high
      level of IL-10 [A. O'Garra, R. Chang, N. Go, R. Hastings, G. Haughton, M. Howard,
      et al. Ly-1 B (B-1) cells are the main source of B cell-derived interleukin 10.
      Eur J Immunol, 22 (1992) 711-717.] and enhanced antigen presentation capacities
      [C. Mohan, L. Morel, P. Yang, E.K. Wakeland, Accumulation of splenic B1a cells
      with potent antigen-presenting capability in NZM2410 lupus-prone mice. Arthritis
      and Rheumatism, 41 (1998) 1652-1662.], have implicated B-1a cells in
      autoimmunity. This review will discuss the current understandings of their role
      in autoimmune diseases with focus on lupus.

PMID- 16890893
TI  - FoxP3: a genetic link between immunodeficiency and autoimmune diseases.
AB  - It has long been observed that patients with autoimmune diseases also have immune
      deficiency. How these two opposite extremes of immunity can be found in the same
      individual is largely unclear. Here we review the evidence that a FoxP3 defect
      may provide a critical link between autoimmunity and immune deficiency.
      Disruption of FoxP3 results in severe autoimmune syndromes in both human and
      mice. Bone marrow chimera experiments indicate that FoxP3 defects in both
      hematopoietic and non-hematopoietic cells are required for the development of
      severe autoimmune disease. FoxP3 mutation in the hematopoietic cells impairs the
      development of regulatory T cells (Treg). Our data demonstrate that the mutation
      in non-hematopoietic cells results in deficient thymopoiesis. Defective T cell
      production may be an underlying cause of T cell hyperproliferation, which
      together with Treg defects, may lead to fatal autoimmune disease in mouse and
      man.

PMID- 16890897
TI  - Dendritic cell subsets and type I diabetes: focus upon DC-based therapy.
AB  - Type I diabetes (TID) is an autoimmune disease characterized by a T cell-mediated
      destruction of insulin-producing beta cells. The destructive response is believed
      to be caused by a Th1-dominant immune attack targeted to several autoantigens
      including glutamate decarboxylase (GAD) and insulin in the presence of an
      ineffective regulatory response. The development of both the Th1 biased effector
      cells as well as regulatory T-cell response can be guided by dendritic cells
      (DC), professional antigen presenting cells (APC) that efficiently capture and
      process self antigens, and present them to T-cells. These APC can either prime
      effector T cells or activate regulatory T cells depending on the function of the
      DC or perhaps distinct DC subsets. Because DC uniquely orchestrate the delicate
      balance between T cell immunity and regulation, efforts are being made to
      investigate the potential of DC therapy for the prevention and/or treatment of
      autoimmune diseases such as TID through augmentation of regulatory responses. As
      the subset and functional stage of DC appear to be critical for tolerance
      induction, several strategies for engineering these cells are emerging.
      Furthermore, the delineation of T1D-associated target antigens allows for the
      development of antigen-specific DC-based therapy. Here we review recent advances
      and considerations for this exciting approach and discuss the selection of the
      appropriate DC subset, self-peptide, and route of administration for the
      optimization of immunotherapy using these cells.

PMID- 16890896
TI  - Role of anti-DNA antibodies in the pathogenesis of lupus nephritis.
AB  - Despite a good association between anti-DNA autoantibodies and lupus nephritis,
      it is difficult to determine the pathogenic potential of an anti-DNA autoantibody
      response. It is proposed that anti-DNA antibodies can exert their pathogenic
      effects through deposition as immune complexes in the kidney or through the
      recognition of cross-reactive antigens in the kidneys. Several studies in
      literature demonstrate that cross-reactivity of anti-DNA antibodies with kidney
      antigens is critical for their pathogenic potential. This raises the question
      whether DNA is responsible for the activation and selection of B cells generating
      cross-reactive anti-DNA antibodies. Recent studies suggest that antigens other
      than DNA can initiate an antibody response that is cross-reactive with dsDNA.
      Moreover, we and other have demonstrated that lupus nephritis can occur in the
      absence of anti-DNA antibodies. Thus, reactivity to dsDNA should be considered as
      one of the characteristic of polyreactive autoantibodies and not a primary
      requisite for the pathogenesis of lupus nephritis.

PMID- 16890895
TI  - Liver stem cell-derived beta-cell surrogates for treatment of type 1 diabetes.
AB  - Consistent with the common embryonic origin of liver and pancreas as well the
      similar glucose-sensing systems in hepatocytes and pancreatic beta-cells, it
      should not be surprising that liver stem cells/hepatocytes can transdifferentiate
      into insulin-producing cells under high-glucose culture conditions or by genetic
      reprogramming. Persistent expression of the pancreatic duodenal homeobox-1 (Pdx1)
      transcription factor or its super-active form Pdx1-VP16 fusion protein in hepatic
      cells reprograms these cells into pancreatic beta-cell precursors. In vitro
      culture at elevated glucose concentrations or in vivo exposure to a hyperglycemia
      are required for further differentiation and maturation of liver-derived
      pancreatic beta-cell precursor into functional insulin-producing pancreatic beta
      like cells. Under appropriate conditions, multiple pancreatic transcription
      factors can work in concert to reprogram liver stem/adult liver cells into
      functional insulin-producing cells. If such autologous liver-derived insulin
      producing cells can be made to escape the type 1 diabetes-associated
      autoimmunity, they may serve as a valuable cell source for future cell
      replacement therapy without the need for life-long immunosuppression.

PMID- 16890898
TI  - Autoantibody markers for the diagnosis and prediction of type 1 diabetes.
AB  - Type 1 diabetes results from the autoimmune destruction of the insulin producing
      pancreatic beta-cells. For years, the notion that T-lymphocytes played a crucial
      role in the disorder's formation was considered such sound dogma, that interest
      in B-lymphocytes and autoantibodies as pathogenic variables was largely relegated
      to second-class status. However, much of our knowledge regarding the pathogenesis
      and natural history of this disease has been afforded by analysis of subjects
      having type 1 diabetes associated autoantibodies. While autoantibodies to more
      than two dozen autoantigens have been associated with this disease, a majority of
      interest has been directed at four autoantibodies; islet cell cytoplasmic (ICA),
      insulin (IAA), glutamic acid decarboxylase (GADA), and IA2/ICA512 autoantigen
      (IA2A). These autoantibodies, combined with other metabolic and genetic markers,
      are extremely effective for predicting eventual development of type 1 diabetes in
      otherwise healthy individuals. These autoantibodies have also aided in our
      understanding of disease heterogeneity and suggest that the autoimmune processes
      underlying type 1 diabetes initiate in the earliest stages of life (e.g., initial
      autoantibody formation at 9-18 months of age). Additional improvements are needed
      to more accurately define the time to disease onset, response to therapeutic
      intervention, the pathogenic features of the autoimmune response, and perhaps
      even the quantity of residual beta cell function.

PMID- 16890899
TI  - Role of non-protein amino acid L-canavanine in autoimmunity.
AB  - Association of SLE and alfalfa was first reported in a volunteer who developed
      lupus-like autoimmunity while ingesting alfalfa seed for a hypercholesterolemia
      study. This was corroborated with studies in monkeys fed with alfalfa sprout that
      developed SLE. Re-challenge with L-canavanine relapsed the disease. Arginine
      homologue L-canavanine, present in alfalfa, was suspected as a cause. L
      canavanine can be charged by arginyl tRNA synthetase to replace L-arginine during
      protein synthesis. Aberrant canavanyl proteins have disrupted structure and
      functions. Induction or exacerbation of SLE by alfalfa tablets reported in a few
      cases remains controversial. Epidemiological studies on the relationship between
      alfalfa and SLE are sparse. In mice, NZB/W F1, NZB, and DBA/2 mice fed with L
      canavanine show exacerbation/triggering of the SLE, however, BALB/c studies were
      negative. L-canavanine incorporation may be more efficient in the presence of
      inflammation or other conditions that can cause arginine deficiency. The L
      canavanine induced apoptotic cells can be phagocytosed and a source of
      autoantigens processed by endosomal proteases. Endogenous canavanyl proteins are
      ubiquitinated and processed via proteasome. Incorporation of L-canavanine into
      proteasome or endosome can also cause disruption of antigen processing. Alfalfa/L
      canavanine-induced lupus will be an interesting model of autoimmunity induced by
      the modification of self-proteins at the translational level.

PMID- 16890900
TI  - Maternal death--a time for reflection.

PMID- 16890901
TI  - Continuity of carer and partnership. A review of the literature.
AB  - The purpose of this paper was to conduct a critical review of the literature to
      determine whether there is convincing evidence that continuity of carer is
      fundamental to midwives forming a partnership relationship with women. Electronic
      databases and text were searched. The research findings did not support the
      notion that continuity of carer was a high priority of the women nor was it found
      to be a clear predictor for women's satisfaction. Continuity of care throughout
      the childbirth experience was found to increase midwives job satisfaction and
      autonomy but did not necessarily lead to midwives developing meaningful
      relationships with women. The lack of research support for continuity of care may
      be a matter of lack of well-designed studies or it may be a real finding. Further
      research is required to determine whether continuity of carer is essential to the
      partnership relationship.

PMID- 16890902
TI  - Birth Territory: a theory for midwifery practice.
AB  - The theory of Birth Territory describes, explains and predicts the relationships
      between the environment of the individual birth room, issues of power and
      control, and the way the woman experiences labour physiologically and
      emotionally. The theory was synthesised inductively from empirical data generated
      by the authors in their roles as midwives and researchers. It takes a critical
      post-structural feminist perspective and expands on some of the ideas of Michel
      Foucault. Theory synthesis was also informed by current research about the
      embodied self and the authors' scholarship in the fields of midwifery, human
      biology, sociology and psychology. In order to demonstrate the significance of
      the theory, it is applied to two clinical stories that both occur in hospital but
      are otherwise different. This analysis supports the central proposition that when
      midwives use 'midwifery guardianship' to create and maintain the ideal Birth
      Territory then the woman is most likely to give birth naturally, be satisfied
      with the experience and adapt with ease in the post-birth period. These benefits
      together with the reduction in medical interventions also benefit the baby. In
      addition, a positive Birth Territory is posited to have a broader impact on the
      woman's partner, family and society in general.

PMID- 16890904
TI  - Modeling local flotation frequency in a turbulent flow field.
AB  - Despite the significance of turbulent fluid motion for enhancing the flotation
      rate in several industrial processes, there is no unified approach to the
      modeling of the flotation rate in a turbulent flow field. Appropriate modeling of
      the local flotation (bubble-particle attachment) rate is the basic constituent
      for global modeling and prediction of flotation equipment efficiency. Existing
      approaches for the local flotation rate are limited to specific set of conditions
      like high or low turbulence. In addition, the combined effects of buoyant bubble
      rise and/or particle gravity settling are usually ignored. The situation is even
      vaguer for the computation of collision and attachment efficiencies which are
      usually computed using the gravity induced velocities although the dominant mode
      of flotation is the turbulent one. The scope of this work is clear: the
      development of a general expression for the flotation rate in a turbulent flow
      field which will cover in a unified and consistent way all possible sets of the
      problem parameters. This is achieved by using concepts from statistical approach
      to homogeneous turbulence and gas kinetic theory.

PMID- 16890905
TI  - On-column activation of bovine recombinant metalloproteinase 20.

PMID- 16890903
TI  - Flashback to the 1960s: utility of archived sera to explore the origin and
      evolution of Plasmodium falciparum chloroquine resistance in the Pacific.
AB  - The increasing frequencies of Plasmodium falciparum strains that are resistant to
      chloroquine (CQ) and other antimalarials are resulting in a global resurgence of
      malaria morbidity and mortality. CQ resistance (CQR) is associated with multiple
      mutations in the P. falciparum chloroquine resistance transporter (pfcrt) gene.
      The mode and tempo of the accumulation of substitutions leading to these complex
      CQR haplotypes remain speculative due to the dearth of samples temporally
      spanning the evolution of drug resistance. The origin and evolution of the CQR
      alleles of Papua New Guinea (PNG) is particularly ambiguous. It remains unclear
      whether the pfcrt haplotype in PNG resulted from an independent origin of a CQR
      haplotype identical in sequence to the South American haplotype, or if this
      haplotype originated in South America and recombined into a Southeast Asian
      derived genome. We sequenced a segment of pfcrt exon 2 from 398 plasmid clones
      derived from archival human sera collected in the Pacific before and after the
      first reported cases of CQ treatment failure (n=251) and modern samples (n=147).
      None of the 251 pfcrt plasmid clones from nine archival samples displayed the
      C72S or the K76T mutations that are characteristic of CQR strains. In contrast,
      these two amino acid substitutions were present in all 147 pfcrt plasmid clones
      from five samples collected between 2001 and 2003; thus, the archival samples
      represent the baseline parasite genetic diversity before the evolution of CQR
      strains. We are currently expanding our analyses to include additional samples
      from the series described here and from series collected in the 1970s and the
      1980s to evaluate the geographic origin of CQR strains in the Pacific and the
      validity of the sequential point mutation accumulation model of CQR evolution.

PMID- 16890907
TI  - Presence of mutans streptococci and Candida spp. in dental plaque/dentine of
      carious teeth and early childhood caries.
AB  - This study determined the presence of mutans streptococci and Candida spp. in
      supragingival dental plaque and infected dentine of caries-free children, with
      early childhood caries and caries. Pooled samples of dental plaque and infected
      dentine were collected from 56 children aged 1-5 years, which were divided into 3
      groups: early childhood caries (ECC); caries and caries-free. Infected dentine
      was collected in ECC and caries groups to compare the frequency of these
      microorganisms in the collected sites. The samples were inoculated in SB20 and SA
      medium, for mutans streptococci and Candida spp., respectively, and incubated at
      37 degrees C for 48 h. Colony growth was verified and the identification was
      performed by biochemical tests and CHROMagar Candida. Fisher's test or chi-square
      (chi(2)) were applied (p=0.05). The more prevalent species were S. mutans and
      Candida albicans in ECC (85.4% and 60.4%, respectively), independently of the
      sample site. S. mutans only was significantly associated with carious teeth,
      whether in early childhood caries or not. However, the frequency of C. albicans
      in ECC was higher when compared to caries and caries-free groups. There is a
      significant association between the presence of C. albicans and early childhood
      caries.

PMID- 16890906
TI  - Dye-induced aggregation of single stranded RNA: a mechanistic approach.
AB  - The binding of proflavine (D) to single stranded poly(A) (P) was investigated at
      pH 7.0 and 25 degrees C using T-jump, stopped-flow and spectrophotometric
      methods. Equilibrium measurements show that an external complex PD(I) and an
      internal complex PD(II) form upon reaction between P and D and that their
      concentrations depend on the polymer/dye concentration ratio (C(P)/C(D)). For
      C(P)/C(D)<2.5, cooperative formation of stacks external to polymer strands
      prevails (PD(I)). Equilibria and T-jump experiments, performed at I=0.1M and
      analyzed according to the Schwarz theory for cooperative binding, provide the
      values of site size (g=1), equilibrium constant for the nucleation step (K(
      *)=(1.4+/-0.6)x10(3)M(-1)), equilibrium constant for the growth step (K=(1.2+/
      0.6)x10(5)M(-1)), cooperativity parameter (q=85) and rate constants for the
      growth step (k(r)=1.2x10(7)M(-1)s(-1), k(d)=1.1 x 10(2)s(-1)). Stopped-flow
      experiments, performed at low ionic strength (I=0.01 M), indicate that
      aggregation of stacked poly(A) strands do occur provided that C(P)/C(D)<2.5.

PMID- 16890908
TI  - The metal-binding sites of the zinc-transporting P-type ATPase of Escherichia
      coli. Lys693 and Asp714 in the seventh and eighth transmembrane segments of ZntA
      contribute to the coupling of metal binding and ATPase activity.
AB  - ZntA is a P-type ATPase which transports Zn(2+), Pb(2+) and Cd(2+) out of the
      cell. Two cysteine-containing motifs, CAAC near the N-terminus and CPC in
      transmembrane helix 6, are involved in binding of the translocated metal. We have
      studied these motifs by mutating the cysteines to serines. The roles of two other
      possible metal-binding residues, K(693) and D(714), in transmembrane helices 7
      and 8, were also addressed. The mutation CAAC-->SAAS reduces the ATPase activity
      by 50%. The SAAS mutant is phosphorylated with ATP almost as efficiently as the
      wild type. However, its phosphorylation with P(i) is poorer than that of the wild
      type and its dephosphorylation rate is faster than that of the wild type ATPase.
      The CPC-->SPS mutant is inactive but residual phosphorylation with ATP could
      still be observed. The most important findings of this work deal with the
      prospective metal-binding residues K(693) and D(714): the substitution K693N
      eliminates the Zn(2+)-stimulated ATPase activity completely, although significant
      Zn(2+)-dependent phosphorylation by ATP remains. The K693N ATPase is
      hyperphosphorylated by P(i). ZntA carrying the change D714M has strong metal
      independent ATPase activity and is very weakly phosphorylated both by ATP and
      P(i). In conclusion, K(693) and D(714) are functionally essential and appear to
      contribute to the metal specificity of ZntA, most probably by being parts of the
      metal-binding site made up by the CPC motif.

PMID- 16890909
TI  - Is the delay discounting paradigm useful in understanding social anxiety?
AB  - The delay discounting paradigm was used to examine its utility in understanding
      motivational factors among socially anxious individuals. Participants (n=88) who
      reported high and low levels of social anxiety were randomly assigned to either a
      social threat or non-threat condition and their subsequent rates of discounting
      were examined. A significant difference in rates of discounting was found between
      the high and low social anxiety groups within the non-threat condition, with high
      social anxiety participants showing increased discounting. This study suggests
      that a modified version of the delay discounting paradigm may be useful in
      understanding motivational factors in social anxiety.

PMID- 16890910
TI  - Monoallelic expression of MAOA in skin fibroblasts.
AB  - X chromosome inactivation in mammalian females occurs early in embryonic
      development and renders most genes on the inactive X chromosome transcriptionally
      silenced. As a consequence, females will display an X chromosomal parent-of
      origin mosaiscism with regard to which parental allele that is expressed. Some
      genes, however, escape inactivation and will therefore be expressed from both
      alleles. In this study, we have investigated if the X-linked MAO-A gene has bi-
      or mono-allelic expression. This information would indicate whether or not MAO-A
      gene dosage could potentially explain the observed gender differences that show
      functional connections to the serotonin system, such as aggression, and
      impulsiveness. To investigate the X inactivation status of MAO-A we have used
      primary clonal cell cultures, on which allelic expression was assessed with RFLP
      analysis. Our results show that the MAO-A gene has mono-allelic expression in
      these cells. This could have important implications for understanding traits that
      display gender differences.

PMID- 16890911
TI  - mtDNA mutation C1494T, haplogroup A, and hearing loss in Chinese.
AB  - Mutation C1494T in mitochondrial 12S rRNA gene was recently reported in two large
      Chinese families with aminoglycoside-induced and nonsyndromic hearing loss
      (AINHL) and was claimed to be pathogenic. This mutation, however, was first
      reported in a sample from central China in our previous study that was aimed to
      reconstruct East Asian mtDNA phylogeny. All these three mtDNAs formed a subclade
      defined by mutation C1494T in mtDNA haplogroup A. It thus seems that mutation
      C1494T is a haplogroup A-associated mutation and this matrilineal background may
      contribute a high risk for the penetrance of mutation C1494T in Chinese with
      AINHL. To test this hypothesis, we first genotyped mutation C1494T in 553
      unrelated individuals from three regional Chinese populations and performed an
      extensive search for published complete or near-complete mtDNA data sets (>3000
      mtDNAs), we then screened the C1494T mutation in 111 mtDNAs with haplogroup A
      status that were identified from 1823 subjects across China. The search for
      published mtDNA data sets revealed no other mtDNA besides the above-mentioned
      three carrying mutation C1494T. None of the 553 randomly selected individuals and
      the 111 haplogroup A mtDNAs was found to bear this mutation. Therefore, our
      results suggest that C1494T is a very rare event. The mtDNA haplogroup A
      background in general is unlikely to play an active role in the penetrance of
      mutation C1494T in AINHL.

PMID- 16890912
TI  - Pharmacological characterization of NAADP-induced Ca2+ signals in starfish
      oocytes.
AB  - The recently discovered second messenger nicotinic acid adenine dinucleotide
      phosphate (NAADP) is central to the onset of intracellular Ca2+ signals induced
      by several stimuli, including fertilization. The nature of the Ca2+ pool
      mobilized by NAADP is still controversial. Depending on the cell type, NAADP may
      target either an acidic compartment with lysosomal properties or ryanodine
      receptors (RyRs) on endoplasmic reticulum. In addition, NAADP elicits a robust
      Ca2+ influx into starfish oocytes by activating a Ca2+-mediated current across
      the plasma membrane. In the present study, we employed the single-electrode
      intracellular recording technique to assess the involvement of either acidic
      organelles or RyRs in NAADP-elicited Ca2+ entry. We found that neither drugs
      which interfere with acidic compartments nor inhibitors of RyRs affected NAADP
      induced depolarization. These data further support the hypothesis that a yet
      unidentified plasma membrane Ca2+ channel is the target of NAADP in starfish
      oocytes.

PMID- 16890913
TI  - Microscopic calculations of local lipid membrane permittivities and diffusion
      coefficients for application to electroporation analyses.
AB  - Interaction of electric fields with biological systems has begun to receive
      considerable attention for applications that include field-assisted drug
      delivery, medical interventions, and genetic engineering. External fields induce
      the strongest effects at membranes with electroporation being a common feature.
      Membrane transport in this context of poration is often based on continuum
      approaches utilizing macroscopic parameters such as the permittivity, diffusion
      coefficients, and mobilities. In such modeling, field dependences, local
      inhomogeneities, and microscopic details are usually ignored. Here, a molecular
      dynamics (MD) scheme is used for a more rigorous and physically realistic
      evaluation of such parameters for potential application to electroporative
      transport model development. A suitable membrane structure containing a nanopore
      derived from MD analysis is used as the initial geometric configuration. Both
      static and frequency dependent diffusion coefficients have been evaluated.
      Permittivities are also calculated and shown to be dramatically non-uniform in
      the vicinity of membranes under high external fields. A positive feedback
      mechanism leading to enhanced membrane fields is discussed.

PMID- 16890914
TI  - Protein misfolding cyclic amplification as a rapid test for assessment of prion
      inactivation.
AB  - Abnormal isoform of prion proteins (PrP(Sc)), which are infectious agents
      associated with prion diseases, retain infectivity after undergoing routine
      sterilization processes. A sensitive method to detect the infectivity is a
      bioassay, and it has been used for assessing prion inactivation. However, the
      result is obtained after several hundred days. Here, protein misfolding cyclic
      amplification (PMCA) in which PrP(Sc) can be amplified in vitro was applied for
      assessing prion inactivation by dry heating and autoclaving. Scrapie-infected
      hamster brains were inactivated under various conditions, and residual
      infectivity and PrP(Sc) were detected by the bioassay and PMCA, respectively. The
      PMCA results were in good agreement with those of the bioassay. In samples
      autoclaved at temperatures below 150 degrees C, while infected mice died in the
      bioassay, protease-resistant PrP (PrP(res)) signals were detected in the second
      or third round of PMCA. Three rounds of PMCA require only 6 days, which means
      that the PMCA method is much faster than the bioassay.

PMID- 16890915
TI  - Wortmannin delays transfer of human rhinovirus serotype 2 to late endocytic
      compartments.
AB  - Human rhinovirus 2 (HRV2) is internalized by members of the low-density
      lipoprotein receptor family into early endosomes (pH 6.2-6.0) where it
      dissociates from its receptors. After transfer into late endosomes, the virus
      undergoes a conformational change and RNA uncoating solely induced by pH < 5.6.
      Finally, virus capsids are degraded in lysosomes. To investigate the role of
      phosphatidylinositol 3-kinases (PI3K) in the HRV2 entry route, we used the
      inhibitor wortmannin. Although virus internalization was not altered by
      wortmannin, virus accumulated in enlarged early endosomes. Furthermore, the drug
      delayed HRV2 degradation and viral protein synthesis. Consequently, wortmannin
      sensitive PI3K are involved in HRV2 transport from early to late compartments.
      However, wortmannin had no effect on the titer of infectious virus produced. Our
      data therefore suggest that virus retained in early endosomes for prolonged time
      periods can undergo the conformational change that otherwise occurs at pH < or =
      5.6 in late endosomes.

PMID- 16890916
TI  - Polyamine synthesis and salvage pathways in the malaria parasite Plasmodium
      falciparum.
AB  - We demonstrate, for the first time, a functional polyamine biosynthetic pathway
      in the malaria parasite Plasmodium falciparum that culminates in the synthesis of
      spermine. Additionally, we also report putrescine and spermidine salvage in the
      malaria parasite. Putrescine and spermidine transport in P. falciparum infected
      red blood cells is a highly specific, carrier mediated and active process,
      mediated by new transporters that differ from the transporters of uninfected red
      blood cells in their kinetic parameters, Vmax and km, as well as in their
      activation energy.

PMID- 16890918
TI  - Simvastatin prolongs survival times in prion infections of the central nervous
      system.
AB  - Prion diseases are fatal and at present there are neither cures nor palliative
      therapies known/available, which delay disease onset or progression. Cholesterol
      lowering drugs have been reported to inhibit prion replication in infected cell
      cultures and to modulate inflammatory reactions. We aimed to determine whether
      simvastatin-treatment could delay disease onset in a murine prion model. Groups
      of mice were intracerebrally infected with two doses of scrapie strain 139A.
      Simvastatin-treatment commenced 100 days postinfection. The treatment did not
      affect deposition of misfolded prion protein PrP(res). However, expression of
      marker proteins for glia activation like major histocompatibility class II and
      galectin-3 was found to be affected. Analysis of brain cholesterol synthesis and
      metabolism revealed a mild reduction in cholesterol precursor levels, whereas
      levels of cholesterol and cholesterol metabolites were unchanged. Simvastatin
      treatment significantly delayed disease progression and prolonged survival times
      in established prion infection of the CNS (p < or = 0.0003). The results suggest
      that modulation of glial responses and the therapeutic benefit observed in our
      murine prion model of simvastatin is not due to the cholesterol-lowering effect
      of this drug.

PMID- 16890917
TI  - Coronary artery disease and a functional polymorphism of hTERT.
AB  - Genetic variation, a -1327T/C polymorphism, of human telomerase reverse
      transcriptase (hTERT) is associated with leukocyte telomere length in healthy
      subjects, but clinical significances of this functional polymorphism are not
      clear. Recently, the relationship between the telomere system and coronary artery
      disease (CAD) was reported. We investigated the association between the -1327T/C
      polymorphism and (a) susceptibility to CAD and (b) telomere length in CAD
      patients. In a case-control study, 104 patients confirmed by coronary angiography
      and 115 age- and sex-matched controls were enrolled. There was a higher frequency
      of the -1327C/C genotype in CAD patients (51.9%) compared with controls (36.5%, p
      = 0.0218). Among the 104 CAD patients, leukocyte telomere length in the -1327C/C
      genotype (7.62+/-2.19 kb, mean+/-SD) was shorter than that in the -1327T/C and 
      1327T/T genotypes (8.74+/-2.92, p = 0.0287). These findings suggest that the 
      1327C/C genotype is a genetic risk factor for CAD and relates to shorter telomere
      length among CAD patients.

PMID- 16890919
TI  - Effect of salivary proteins on the transport of tannin and quercetin across
      intestinal epithelial cells in culture.
AB  - Polyphenols including tannins and flavonoids are common in plant foods. While
      tannins may be deleterious to animals, flavonoids can have beneficial effects on
      the cardio-vascular system. Since salivary proteins can form complexes with
      polyphenols and thereby interfere with their intestinal absorption, the effect of
      salivary proteins on transport of tannins and flavonoids across intestinal
      epithelial cells (Caco-2 cells) was investigated. In presence of the salivary
      protein Histatin5 (Hst5) the rate of transport (dC/dt) of pentagalloyl glucose
      (5GG), a tannic acid, across Caco-2 cells in culture was reduced maximally 3.6
      fold to 5x10(-7)microM/s in apical to basolateral direction. Replacing the
      basolateral salt solution with serum caused a 13-fold increase in dC/dt of 5GG in
      the absence of Hst5, but addition of Hst5 decreased dC/dt l4-fold. Transport of
      5GG in basolateral to apical direction was decreased in half in the presence of
      Hst5. Decreases in dC/dt were closely paralleled by formation of insoluble 5GG
      Hst5 complexes. In contrast, Hst5 and 1B4, a salivary proline-rich protein, had
      little if any effect on the transepithelial transport of the flavonoid quercetin
      in apical to basolateral as well as basolateral to apical direction. Taken
      together with previous studies [Cai K, Hagerman AE, Minto RE, Bennick A.
      Decreased polyphenol transport across cultured intestinal cells by a salivary
      proline-rich protein. Biochem Pharmacol 2006;71:1570-80] it appears that although
      Hst5 and 1B4 are synthesized in salivary glands they have an important biological
      function in the intestines as scavenger molecules preventing uptake of tannin but
      without notably affecting absorption of flavonoids.

PMID- 16890921
TI  - The mesencephalic trigeminal sensory nucleus is involved in acquisition of active
      exploratory behavior induced by changing from a diet of exclusively milk formula
      to food pellets in mice.
AB  - Post-weaning mice fed exclusively milk display low-frequency exploratory behavior
      [Ishii, T., Itou, T., and Nishimura, M. (2005) Life Sci. 78, 174-179] compared to
      mice fed a food pellet diet. This low-frequency exploratory behavior switched to
      high-frequency exploration after a switch from exclusively milk formula to a food
      pellet diet. Acquisition of the high-frequency exploratory behavior was
      irreversible. Recently, we demonstrated that the mesencephalic trigeminal nucleus
      (Me5) is involved in the control of feeding and exploratory behavior in mice
      without modulating the emotional state [Ishii, T., Furuoka, H., Itou, T.,
      Kitamura, N., and Nishimura, M. (2005) Brain Res. 1048, 80-86]. We therefore
      investigated whether the Me5 is involved in acquisition of high-frequency
      exploratory behavior induced by the switch in diet from an exclusively milk
      formula to food pellets. Mouse feeding and exploratory behaviors were analyzed
      using a food search compulsion apparatus, which was designed to distinguish
      between the two behaviors under standard living conditions. Immunohistochemical
      analysis of immediate early genes indicated that the Me5, which receives signals
      from oral proprioceptors, is transiently activated after the diet change. The
      change from low-frequency to high-frequency exploratory behavior was prevented in
      milk-fed mice by bilateral lesion of the Me5. These results suggest that the Me5
      is activated by signals associated with mastication-induced proprioception and
      contributes to the acquisition of active exploratory behavior.

PMID- 16890920
TI  - Bax and Bcl-2 expression and TUNEL labeling in lumbar enlargement of neonatal
      rats after sciatic axotomy and melatonin treatment.
AB  - Peripheral axotomy in neonatal rats induces neuronal death. We studied the anti
      apoptotic protein Bcl-2 and cell death promoter Bax in spinal cord of neonatal
      rats after sciatic transection and treatment with melatonin, a neuroprotective
      substance. Pups were unilaterally axotomized at P2 and received melatonin (1
      mg/kg; sc) or vehicle 1 h prior to lesion, immediately after, at 1 h, 2 h and
      then once daily. Rats were sacrificed at 3 h, 6 h, 24 h, 72 h and 5 days
      postaxotomy. Intact animals were used as controls. Lumbar enlargement was
      processed for Nissl staining, immunohistochemistry and RT-PCR for Bax or Bcl-2
      and TUNEL reaction. Motoneurons (MN) of lesioned (L) and normal (N) sides were
      counted, and MN survival ratio (MSR=L/N) was calculated. Bax and Bcl-2 showed
      cytoplasmic immunoreactivity (IR). Bax IR was noticeable in small cells but less
      evident in MN. In unlesioned pups, some Bax-positive small cells (B+) and TUNEL
      positive nuclei (T+) were mainly seen in the dorsal horn. In lesioned animals
      given vehicle, Bax mRNA levels and numbers of B+ and T+ were increased in
      comparison with intact controls at 24 h postaxotomy. The basal IR for Bax in MN
      was not changed by axotomy. Bcl-2 IR was noted in all cells and, like Bcl-2 mRNA,
      was unaltered after lesion. Melatonin reduced MN loss at 24 h, 72 h and 5 days
      and T+ at 24 h after lesion but did not interfere with Bax or Bcl-2 expression.
      These results suggest that (1) sciatic transection at P2 increases Bax mRNA and
      the amount of B+ and T+ in the lumbar enlargement, (2) Bax IR in immature MN is
      not altered by axotomy and (3) melatonin protects MN and dorsal horn cells
      through a mechanism independent of Bax and Bcl-2.

PMID- 16890922
TI  - Caspase-dependent cell death involved in brain damage after acute subdural
      hematoma in rats.
AB  - Traumatic brain injury is associated with acute subdural hematoma (ASDH) that
      worsens outcome. Although early removal of blood can reduce mortality, patients
      still die or remain disabled after surgery and additional treatments are needed.
      The blood mass and extravasated blood induce pathomechanisms such as high
      intracranial pressure (ICP), ischemia, apoptosis and inflammation which lead to
      acute as well as delayed cell death. Only little is known about the basis of
      delayed cell death in this type of injury. Thus, the purpose of the study was to
      investigate to which extent caspase-dependent intracellular processes are
      involved in the lesion development after ASDH in rats. A volume of 300microL
      blood was infused into the subdural space under monitoring of ICP and tissue
      oxygen concentration. To asses delayed cell death mechanisms, DNA fragmentation
      was measured 1, 2, 4 and 7 days after ASDH by TUNEL staining, and the effect of
      the pan-caspase inhibitor zVADfmk on lesion volume was assessed 7 days post-ASDH.
      A peak of TUNEL-positive cells was found in the injured cortex at day 2 after
      blood infusion (53.4+/-11.6 cells/mm(2)). zVADfmk (160ng), applied by
      intracerebroventricular injection before ASDH, reduced lesion volume
      significantly by more than 50% (vehicle: 23.79+/-7.62mm(3); zVADfmk: 9.06+/
      4.08). The data show for the first time that apoptotic processes are evident
      following ASDH and that caspase-dependent mechanisms play a crucial role in the
      lesion development caused by the blood effect on brain tissue.

PMID- 16890923
TI  - Pharmacological manipulations of food protection behavior in rats: evidence for
      dopaminergic contributions to time perception during a natural behavior.
AB  - Operant procedures combined with pharmacological manipulations have implicated a
      role for the dopaminergic system in the perception and production of temporal
      intervals. Because studies have suggested that animals use temporal information
      to organize food protection behavior, the current study investigates whether
      dopaminergic systems are involved in timing during this natural behavior. The
      experiment examined the influence of a dopaminergic agonist (amphetamine) and an
      antagonist (haloperidol) on food protection behavior initiated to avoid theft by
      a conspecific. Amphetamine increased the time spent dodging and decreased the
      time spent bracing during the consumption of a hazelnut. On the other hand,
      haloperidol decreased the time spent dodging while showing no systematic changes
      in bracing. Topographic and kinematic analyses of rat movement conflicted with
      motivational, motoric, and social accounts of drug-induced changes in food
      protection behavior organization. These observations provide evidence that rats
      use temporal information to organize movements in the natural behavior of
      protecting food from theft by a conspecific, and this organization is influenced
      by both a dopaminergic agonist and an antagonist.

PMID- 16890925
TI  - Common variants of Cholesteryl ester transfer protein gene and their association
      with lipid parameters in healthy volunteers of Tamilian population.
AB  - BACKGROUND: Cholesteryl ester transfer protein (CETP) is involved in a key
      pathway of reverse cholesterol transport implicated in atherosclerosis and
      coronary heart disease. CETP gene is known to have many single nucleotide
      polymorphisms which have been associated with CETP activity and plasma high
      density lipoprotein cholesterol (HDL-C) concentrations. No data on the prevalence
      of these polymorphisms and their phenotypic association is available in South
      Indian population. METHODS: Three CETP polymorphisms: TaqIB, -629C/A and I405V
      were studied in 171 healthy volunteers from Tamilnadu, a major population of
      South India. Subjects were clinically examined and lipid profile was estimated.
      Genotyping was performed by PCR-RFLP and genotype frequencies estimated. RESULTS:
      The allele frequencies of TaqIB: B1 allele was 0.51; -629C/A: C allele was 0.36;
      and that of I405V: I allele was 0.47. Study of association between these three
      polymorphisms and plasma lipid concentrations revealed no significant differences
      in lipid parameters between genotypes. A gender based subgroup analysis revealed
      a significant increase in HDL-C in men with B2B2 genotype and decrease in TG in
      B1B2 genotype. Analysis of the combined effect of multiple mutant genotypes
      revealed that as the number of mutant genotypes increased, the concentrations of
      low density lipoprotein-cholesterol (LDL-C), HDL-C and total cholesterol (TC)
      increased whereas that of triglyceride (TG) decreased in the group of three
      mutant genotypes significantly. CONCLUSION: The frequency of B2 and A alleles of
      TaqIB and -629C/A polymorphisms were highest in Tamilian population when compared
      to other major ethnic groups while that of V allele of I405V polymorphism is
      between Caucasians and African Americans. Taq1B polymorphism was associated with
      HDL-C and TG concentrations only in men. Combination of these three polymorphisms
      was significantly associated with lipid profile than the individual
      polymorphisms.

PMID- 16890924
TI  - Modulation of MOG 37-50-specific CD8+ T cell activation and expansion by CD43.
AB  - Several recent reports have described an effector role for CD8(+) T cells during
      EAE. We have previously demonstrated reduced disease incidence and severity in
      CD43(-/-) mice following MOG immunization, and attributed this attenuation in
      disease progression to the effects of CD43 deficiency on CD4+ T cells. Here, we
      extend those studies to examine the effects of the loss of CD43 on MOG-specific
      CD8+ T cells. A reduced frequency of MOG-specific CD8+ T cells following
      immunization was observed in CD43(-/-) mice relative to wild-type controls, as
      demonstrated by intracellular cytokine and MHC tetramer staining. In addition,
      adoptive transfer of CD8+ MOG 35-55-primed LN cells from CD43(-/-) mice resulted
      in significantly attenuated EAE induction as compared to recipients of wild-type
      CD8+ MOG-primed cells. Analysis of intracellular signaling intermediates revealed
      a deficiency in the ability of MOG-specific CD8+ T cells to phosphorylate ERK in
      response to antigen. These results characterize an important role for CD43 during
      the activation and expansion of autoreactive MOG-specific CD8+ T cells.

PMID- 16890926
TI  - The distribution of fasting and non-fasting serum triglyceride levels in Japanese
      population.

PMID- 16890928
TI  - Wnt signaling in hydroid development: formation of the primary body axis in
      embryogenesis and its subsequent patterning.
AB  - We have studied the role the canonical Wnt pathway plays in hydroid pattern
      formation during embryonic development and metamorphosis. Transcripts of Wnt and
      Tcf were asymmetrically deposited in the oocyte and subsequent developmental
      stages, marking the sites of first cleavage, posterior larval pole and the
      upcoming head of the metamorphosed polyp. To address the function of these genes,
      we activated downstream events of the Wnt pathway by pharmacologically blocking
      GSK-3beta. These treatments rendered the polar expression of Tcf ubiquitous and
      induced development of ectopic axes that contained head structures. These results
      allow concluding that Wnt signaling controls axis formation and regional tissue
      fates along it, determining one single axis terminus from which later the mouth
      and hypostome develop. Our data also indicate Wnt functions in axis formation and
      axial patterning as in higher metazoans, and thus point to an ancestral role of
      Wnt signaling in these processes in animal evolution.

PMID- 16890929
TI  - The C. elegans HP1 homologue HPL-2 and the LIN-13 zinc finger protein form a
      complex implicated in vulval development.
AB  - HP1 proteins are essential components of heterochromatin and contribute to the
      transcriptional repression of euchromatic genes via the recruitment to specific
      promoters by corepressor proteins including TIF1 and Rb. The Caenorhabditis
      elegans HP1 homologue HPL-2 acts in the "synMuv" (synthetic multivulval) pathway,
      which defines redundant negative regulators of a Ras signaling cascade required
      for vulval induction. Several synMuv genes encode for chromatin-associated
      proteins involved in transcriptional regulation, including Rb and components of
      the Mi-2/NuRD and TIP60/NuA4 chromatin remodeling complexes. Here, we show that
      HPL-2 physically interacts in vitro and in vivo with the multiple zinc finger
      protein LIN-13, another member of the synMuv pathway. A variant of the conserved
      PXVXL motif found in many HP1-interacting proteins mediates LIN-13 binding to the
      CSD of HPL-2. We further show by in vivo localization studies that LIN-13 is
      required for HPL-2 recruitment in nuclear foci. Our data suggest that the LIN
      13/HPL-2 complex may physically link a subset of the Rb related synMuv proteins
      to chromatin.

PMID- 16890930
TI  - Planar polarization of the denticle field in the Drosophila embryo: roles for
      Myosin II (zipper) and fringe.
AB  - Epithelial planar cell polarity (PCP) allows epithelial cells to coordinate their
      development to that of the tissue in which they reside. The mechanisms that
      impart PCP as well as effectors that execute the polarizing instructions are
      being sought in many tissues. We report that the epidermal epithelium of
      Drosophila embryos exhibits PCP. Cells of the prospective denticle field, but not
      the adjacent smooth field, align precisely. This requires Myosin II (zipper)
      function, and we find that Myosin II is enriched in a bipolar manner, across the
      parasegment, on both smooth and denticle field cells during denticle field
      alignment. This implies that actomyosin contractility, in combination with
      denticle-field-specific effectors, helps execute the cell rearrangements
      involved. In addition to this parasegment-wide polarity, prospective denticle
      field cells express an asymmetry, uniquely recognizing one cell edge over others
      as these cells uniquely position their actin-based protrusions (ABPs; which
      comprise each denticle) at their posterior edge. Cells of the prospective smooth
      field appear to be lacking proper effectors to elicit this unipolar response.
      Lastly, we identify fringe function as a necessary effector for high fidelity
      placement of ABPs and show that Myosin II (zipper) activity is necessary for ABP
      placement and shaping as well.

PMID- 16890932
TI  - Tissue inhibitor of metalloproteinases 3 regulates extracellular matrix--cell
      signaling during bronchiole branching morphogenesis.
AB  - Tissue inhibitors of metalloproteinases (TIMPs) regulate extracellular matrix
      (ECM) degradation by matrix metalloproteinases (MMPs) throughout embryogenesis.
      We examined lungs from TIMP3 null mice and found decreased bronchiole branching,
      enhanced activity of MMPs and enhanced fibronectin degradation throughout lung
      development compared to controls. Activation of focal adhesion kinase (FAK) was
      also reduced from embryonic days 12.5 through 14.5 in TIMP3 null lungs. Treatment
      with a synthetic MMP inhibitor, GM6001, in utero enhanced the branching pattern
      in both wild type and null lungs accompanied by a restoration of fibronectin
      localization, signaling through FAK and epithelial cell proliferation in null
      lungs. Direct down-regulation of FAK abundance in WT lung organ culture by siRNA
      targeting resulted in reduced bronchiole branching, phenocopying the TIMP3
      defect. We propose that enhanced MMP activity in the absence of TIMP3 interferes
      with focal ECM proteolysis, perturbing the intracellular signaling necessary for
      correct pattern formation of the bronchiole tree during bronchiole branching
      morphogenesis. Thus, TIMP3 can indirectly regulate epithelial cell proliferation
      via MMP inhibitory activity. While others have demonstrated this function for
      MMPs, and there is in vitro evidence that TIMP3 controls proliferation, to our
      knowledge this is the first evidence of TIMP3 regulating proliferation in vivo.

PMID- 16890931
TI  - Functions of the ecdysone receptor isoform-A in the hemimetabolous insect
      Blattella germanica revealed by systemic RNAi in vivo.
AB  - The molecular basis of ecdysteroid function during development has been analyzed
      in detail in holometabolous insects, especially in Drosophila melanogaster, but
      rarely in hemimetabolous. Using the hemimetabolous species Blattella germanica
      (German cockroach) as model, we show that the ecdysone receptor isoform-A (BgEcR
      A) mRNA is present throughout the penultimate and last nymphal instars in all
      tissues analyzed (prothoracic gland, epidermis and fat body). To study the
      functions of BgEcR-A, we reduced its expression using systemic RNAi in vivo, and
      we obtained knockdown specimens. Examination of these specimens indicated that
      BgEcR-A during the last nymphal instar is required for nymphal survival, and that
      reduced expression is associated with molting defects, lower circulating
      ecdysteroid levels and defects in cell proliferation in the follicular
      epithelium. Some BgEcR-A knockdown nymphs survive to the adult stage. The
      features of these specimens indicate that BgEcR-A is required for adult-specific
      developmental processes, such as wing development, prothoracic gland degeneration
      and normal choriogenesis.

PMID- 16890933
TI  - Role of sooty mold fungi in accumulation of fine-particle-associated PAHs and
      metals on deciduous leaves.
AB  - The focus of this research was on elucidation of the role of deciduous tree
      ecosystems in accumulation of fine-particle-associated polycyclic aromatic
      hydrocarbons (PAHs) and heavy metals on leaves of deciduous trees. The studied
      species were Tilia x euchlora (frequently infested by sooty mold fungi) and Pyrus
      calleryana (unaffected by sooty mold fungi). The selected species have similar
      leaf morphology and were exposed to identical environmental conditions. Intra
      species comparison showed that moldy linden leaves accumulate significantly
      higher amounts of PAHs and metals than unaffected linden leaves. Inter-species
      comparison revealed that in the absence of sooty mold fungi, physico-chemical
      properties of epicuticular waxes, rather than the amounts of waxes, might play an
      important role in accumulation of particulate matter on leaves. The accumulation
      and/or degradation of a number of high-molecular-weight (HMW) PAHs on leaves was
      temperature dependent. The results show that the presence of sooty mold fungi on
      deciduous leaves alters either the accumulation modes and/or degradation pathways
      of PAHs on deciduous leaves.

PMID- 16890934
TI  - Selective conjugated fatty acids inhibit guinea pig platelet aggregation.
AB  - Conjugated linoleic acids have been shown to reduce eicosanoid release from
      select tissues and/or cells. To elucidate effects of conjugated linoleic acid
      isomers on cyclooxygenase-1 (COX-1) activity and their application as platelet
      aggregation inhibitors, conjugated linoleic acid isomers and conjugated
      nonadecadienoic acid were incubated with ovine COX-1 and Raw264.7 macrophage to
      examine their effects on COX-1 activity. The effects were further examined in
      collagen and ADP-induced guinea pig whole blood platelet aggregation. Fatty acids
      tested were shown to inhibit COX-1 enzymatic activity. However, only 10t, 12c
      conjugated linoleic acid, 9t, 11t-conjugated linoleic acid and conjugated
      nonadecadienoic acid inhibited collagen and ADP-induced platelet aggregation with
      IC(50) 125.9 microM (74.2 microM to 213.4 microM, 95% confidence interval), 99.3
      microM (52.8 microM to 187.2 microM, 95% confidence interval) and 124.3 microM
      (85.1 microM to 181.5 microM, 95% confidence interval) respectively in collagen
      induced aggregation. TxB(2) release was also appreciably inhibited by 10t, 12c
      conjugated linoleic acid, 9t, 11t-conjugated linoleic acid and conjugated
      nonadecadienoic acid. Based on these data, we conclude 10t, 12c-conjugated
      linoleic acid, 9t, 11t-conjugated linoleic acid and conjugated nonadecadienoic
      acid are platelet aggregation inhibitors while 9c, 11t-conjugated linoleic acid
      is a moderate inhibitor and linoleic acid, and 9c, 11c-conjugated linoleic acid
      have no effect on whole blood platelet aggregation.

PMID- 16890935
TI  - Comparison of the effects of PAR1 antagonists, PAR4 antagonists, and their
      combinations on thrombin-induced human platelet activation.
AB  - Thrombin activates human platelets through proteolytic activation of two protease
      activated receptors (PARs), PAR1 and PAR4. In the present study, we show that,
      RWJ-56110, a potent synthetic PAR1 antagonist, inhibited platelet aggregation
      caused by a low concentration (0.05 U/ml) of thrombin, but lost its effectiveness
      when higher concentrations of thrombin were used as stimulators. YD-3, a non
      peptide PAR4 antagonist, alone had little or no effect on thrombin-induced
      platelet aggregation, significantly enhanced the anti-aggregatory activity of
      PAR1 antagonist. In addition, we demonstrate for the first time that P-selectin
      expression in thrombin-stimulated platelets can be synergistically prevented by
      combined treatment of PAR1 antagonist and PAR4 antagonist. These results indicate
      that thrombin-induced platelet activation cannot be effectively inhibited by just
      blocking either single thrombin receptor pathway, and suggest a rationale for
      potential combination therapy in arterial thrombosis.

PMID- 16890936
TI  - Improvement of walking disturbance by beraprost sodium in rat femoral artery
      occlusion models.
AB  - In rats receiving bilateral femoral arteries ligation (day 0), repeated oral
      administration of the prostacyclin derivative beraprost sodium (50 microg/kg,
      b.i.d.) from day 1 to day 5 resulted in a significant prolongation in walking
      time in rotarod walking exercise performed on day 5. Similarly, results were
      obtained in rats with bilateral femoral arterial thrombosis induced by
      application of FeCl(3)/HCl. In the ligation model, a significant increase was
      observed in femoral/carotid arterial blood pressure ratio even on day 2. These
      results indicated that beraprost sodium improves blood flow and walking
      disturbances associated with arterial occlusion in rats.

PMID- 16890937
TI  - Changes in mGlu5 receptor expression in the basal ganglia of reserpinised rats.
AB  - Dopamine depletion in Parkinson's disease results in a series of
      pathophysiological changes in the basal ganglia circuitry. Increased release of
      glutamate plays an important role in this motor disorder, therefore, agents
      interacting with glutamatergic transmission may have therapeutic potential. In
      this study we investigated changes in both mRNA expression and the number of
      binding sites of the mGlu5 receptor in a reserpinised rat model of Parkinson's
      disease. The in situ hybridisation demonstrated that acute reserpine treatment
      caused a significant decrease in the expression of mGlu5 receptor mRNA in the
      rostral and caudal parts of the rat striatum. At the same time, tritium-labelled
      2-ethyl-6-(phenylethynyl)-pyridine ([(3)H]MPEP) ligand binding experiments
      detected a significant increase in the total number of mGlu5 receptors in the
      same region of the motor loop. These apparently contradictory data can be
      explained by mGlu5 receptor turnover being down-regulated in reserpinised rats,
      due possibly to an imbalance in the rates of synthesis/insertion and
      internalisation/degradation of the receptor. These findings suggest that changes
      such as these affecting mGlu5 receptors may be involved in the pathophysiological
      consequences of dopamine depletion in the brain.

PMID- 16890938
TI  - Peculiar labeling of cultured hippocampal neurons by different sera harboring
      anti-glutamic acid decarboxylase autoantibodies (GAD-Ab).
AB  - Immunological derangement is assumed to be present in a subgroup of patients
      affected by drug-resistant epilepsy with serum harboring anti-glutamic acid
      decarboxylase autoantibodies (GAD-Ab). To further investigate the specific
      reactivity of GAD-Ab with target cells, we tested sera from drug-resistant
      epileptics harboring GAD-Ab on cultured fetal rat hippocampal neurons. As a
      control, we tested sera from GAD-Ab-negative epileptics and GAD-Ab-positive
      patients affected by Stiff Person Syndrome (SPS), ataxia or diabetes. A specific
      pattern of reactivity, varying according to disease, was detected on application
      of sera from GAD-Ab-positive patients with epilepsy, SPS and ataxia, but no
      specific labeling was found on application of sera from patients with GAD-Ab
      negative epilepsy or from GAD-Ab-positive diabetic controls.

PMID- 16890939
TI  - The effect of intrahippocampal insulin microinjection on spatial learning and
      memory.
AB  - Insulin is best known for its action on peripheral target tissues such as the
      adipocyte, muscle and liver to regulate glucose homeostasis. Insulin and its
      receptor are found in specific area of CNS with a variety of region-specific
      functions different from its direct glucose regulation in the periphery. The
      hippocampus and cerebral cortex distributed insulin/insulin receptor has been
      shown to be involved in brain cognitive functions. Previous studies about the
      effect of insulin on memory are controversial. In the present study, the effect
      of insulin microinjection into CA1 region of rat hippocampus on water maze
      performance has been investigated. Insulin had a discrepant effect dose
      dependently. The spatial learning and memory were impaired with lower dose of
      insulin, had not changed with intermediate doses, while they improved with higher
      doses. These results suggest that insulin may have a dose-dependent effect on
      spatial learning and memory.

PMID- 16890941
TI  - Inhibitors of casein kinase 1 block the growth of Leishmania major promastigotes
      in vitro.
AB  - Casein kinase 1 (CK1) is a family of multifunctional Ser/Thr protein kinases that
      are ubiquitous in eukaryotic cells. Recent studies have demonstrated the
      existence of, and role for, CK1 in protozoan parasites such as Leishmania,
      Plasmodium and Trypanosoma. The value of protein kinases as potential drug
      targets in protozoa is evidenced by the successful exploitation of cyclic
      guanosine monophosphate-dependent protein kinase (PKG) with selective tri
      substituted pyrrole and imidazopyridine inhibitors. These compounds exhibit in
      vivo efficacy against Eimeria tenella in chickens and Toxoplasma gondii in mice.
      We now report that both of these protein kinase inhibitor classes inhibit the
      growth of Leishmania major promastigotes and Trypanosoma brucei bloodstream forms
      in vitro. Genome informatics predicts that neither of these trypanosomatids codes
      for a PKG orthologue. Biochemical studies have led to the unexpected discovery
      that an isoform of CK1 represents the primary target of the pyrrole and
      imidazopyridine kinase inhibitors in these organisms. CK1 from extracts of L.
      major promastigotes co-fractionated with [(3)H]imidazopyridine binding activity.
      Further purification of CK1 activity from L. major and characterization via
      liquid chromatography coupled tandem mass spectrometry identified CK1 isoform 2
      as the specific parasite protein inhibited by imidazopyridines. L. major CK1
      isoform 2 expressed as a recombinant protein in Escherichia coli displayed
      biochemical and inhibition characteristics similar to those of the purified
      native enzyme. The results described here warrant further evaluation of the
      activity of these kinase inhibitors against mammalian stage Leishmania parasites
      in vitro and in animal models of infection, as well as studies to genetically
      validate CK1 as a therapeutic target in trypanosomatid parasites.

PMID- 16890940
TI  - Developmental plasticity of HPA and fear responses in rats: a critical review of
      the maternal mediation hypothesis.
AB  - Developmental plasticity of HPA and fear responses in rats has been proposed to
      be mediated by environment-dependent variation in active maternal care. Here, we
      review this maternal mediation hypothesis based on the postnatal manipulation
      literature and on our own recent research in rats. We show that developmental
      plasticity of HPA and fear responses in rats cannot be explained by a linear
      single-factor model based on environment-dependent variation in active maternal
      care. However, by adding environmental stress as a second factor to the model, we
      were able to explain the variation in HPA and fear responses induced by postnatal
      manipulations. In this two-factor model, active maternal care and environmental
      stress (as induced, e.g., by long maternal separations or maternal food
      restriction) exert independent, yet opposing, effects on HPA reactivity and
      fearfulness in the offspring. This accounts well for the finding that completely
      safe and stable, as well as, highly stressful maternal environments result in
      high HPA reactivity and fearfulness compared to moderately challenging maternal
      environments. Furthermore, it suggests that the downregulation of the HPA system
      in response to stressful maternal environments could reflect adaptive
      developmental plasticity based on the increasing costs of high stress reactivity
      with increasingly stressful conditions. By contrast, high levels of environmental
      stress induced by environmental adversity might constrain such adaptive
      plasticity, resulting in non-adaptive or even pathological outcomes.
      Alternatively, however, developmental plasticity of HPA and fear responses in
      rats might be a function of maternal HPA activation (e.g., levels of circulating
      maternal glucocorticoid hormones). Thus, implying a U-shaped relationship between
      maternal HPA activation and HPA reactivity and fearfulness in the offspring,
      increasing maternal HPA activation with increasing environmental adversity would
      explain the effects of postnatal manipulations equally well. This raises the
      possibility that variation in active maternal care is an epiphenomenon, rather
      than a causal factor in developmental plasticity of HPA and fear responses in
      rats. Developmental plasticity of HPA and fear responses in rats and other
      animals has important implications for the design of animal experiments and for
      the well-being of experimental animals, both of which depend on the exact
      underlying mechanism(s). Importantly, however, more naturalistic approaches are
      needed to elucidate the adaptive significance of environment-dependent variation
      of HPA reactivity and fearfulness in view of discriminating between effects
      reflecting adaptive plasticity, phenotypic mismatch and pathological outcomes,
      respectively.

PMID- 16890943
TI  - An anion-exchange chromatographic study on boron isotopic fractionation at 2 MPa
      at 293 K.
AB  - To study boron isotopic fractionation at high pressure, column chromatography
      operated in the breakthrough manner was performed at 2.0 MPa at 25.0 degrees C.
      The fractionation factor (S) between boron adsorbed onto strongly basic anion
      exchange resin and boron in solution was obtained as 1.013, which was smaller
      than the values at 0.1 MPa (atmospheric pressure) found in literature. The
      pressure dependence of S was discussed based on the polymerization of boron in
      the solution and resin phases and on the occurrence of the pressure dependent
      isotope effect relating to the molar volume changes of boron species upon isotope
      substitution.

PMID- 16890942
TI  - Involvement of the c-Ski oncoprotein in cell cycle arrest and transformation
      during nurse cell formation after Trichinella spiralis infection.
AB  - The role of c-Ski, an oncoprotein encoded by the oncogene, c-ski, in Trichinella
      spiralis-infected muscle tissues during nurse cell formation, was investigated by
      following the expression kinetics and distribution of c-Ski (both protein and
      mRNA) in the infected muscle cell, as well as the expression kinetics of the
      transforming growth factor beta (TGF-beta) signaling pathway factor genes (TGF
      beta, Smad2 and Smad4) which cooperate with c-Ski. Immunohistochemical analysis
      using an anti-c-Ski antibody indicated that in the early stages of infection (13
      and 18 days post-infection (p.i.)) the increased expression of the c-Ski protein
      was limited to the eosinophilic cytoplasm and not the enlarged nuclei or
      basophilic cytoplasm. At a later stage of infection (23 and 28 days p.i.) the c
      Ski protein was limited to the enlarged nuclei in the basophilic cytoplasm,
      rather than the eosinophilic cytoplasm. At 48 days p.i., the c-Ski protein was
      barely detectable. Real-time PCR analysis showed that expression of the c-ski
      gene increased from 13 days p.i., reached a peak at 23-28 days p.i. and then
      decreased to a low level by 48 days p.i. Expression kinetics for the TGF-beta
      signaling pathway factor genes (TGF-beta, Smad2 and Smad4) were similar to that
      of c-ski. These findings provide evidence that the c-Ski protein is involved in
      nurse cell formation through the TGF-beta signaling pathway process in the host
      cell nucleus.

PMID- 16890945
TI  - Continuous separation of particles using a microfluidic device equipped with flow
      rate control valves.
AB  - We propose herein an improved microfluidic system for continuous and precise
      particle separation. We have previously proposed a method for particle separation
      called "pinched flow fractionation." Using the previously reported method,
      particles can be continuously separated according to differences in their
      diameters, simply by introducing liquid flows with and without particles into a
      specific microchannel structure. In this study, we incorporated PDMS membrane
      microvalves for flow rate control into the microfluidic device to improve the
      separation accuracy. By adjusting the flow rates distributed to each outlet,
      target particles could be precisely collected from the desired outlet. We
      succeeded in separating micron and submicron-size polymer particles. This method
      can be used widely for continuous and precise separation of various kinds of
      particles, and can function as an important part of microfluidic systems.

PMID- 16890944
TI  - Simultaneous determination of benzophenone-type UV filters in water and soil by
      gas chromatography-mass spectrometry.
AB  - A novel method has been developed to simultaneously determine and quantify seven
      organic UV filters employing liquid (solid)-liquid extraction, derivatization
      with N-methyl-N-(trimethylsilyl) trifluoroacetamide (MSTFA) and gas
      chromatography with mass spectrometric detection in various environmental
      matrices. The UV filters determined were: benzophenone (BP), benzhydrol (BH), 4
      hydroxybenzophenone (HBP), 2-hydroxy-4-methoxybenzophenone (HMB), 2,4
      dihydroxybenzophenone (DHB), 2,2'-dihydroxy-4-methoxybenzophenone (DHMB) and
      2,3,4-trihydroxylbenzophenone (THB). Under optimal conditions, the analysis
      required 23 min and good linearity over the range of 10-2,500 ng/L in water and
      100-25,000 ng/kg in soil for each UV filter obtained. The high recovery (62-114%
      and 60-125% for water and soil samples, respectively) and the low RSD values
      (less than 13.9 and 17.2% for water and soil samples, respectively) indicated the
      high performance of this method. The method detection limits (MDLs) were
      relatively low, ranging from 5 to 100 ng/L or kg and quantification limits ranged
      between 25 and 500 ng/L or kg for all test compounds. This validated method was
      applied in the analysis of seven BP-type UV filters collecting water and soil
      samples in Korea, between April and May 2003. The overall concentration of UV
      filters in the soil sample (500-18,380 ng/kg) was highly distributed in water
      sample (27-204 ng/L). The established method was successfully applied to monitor
      the residue measurement of the BP-type UV filters in environmental water and soil
      samples.

PMID- 16890946
TI  - Influence of the soil matrices on the analytical performance of headspace solid
      phase microextraction for organotin analysis by gas chromatography-pulsed flame
      photometric detection.
AB  - Organotin compounds (OTCs) have been identified in a variety of environmental
      media (air, surface water, groundwater, soil and sediments). In the past, much
      attention was assigned to the study of the OTCs content in biological samples,
      water and sediments. Little information about OTCs in soil is available. In this
      work, a procedure for butyl and phenyltin determination in soils by headspace
      solid-phase microextraction (HS-SPME) gas chromatography-pulsed flame photometric
      detection (GC-PFPD) was investigated. For SPME analysis, a polydimethylsiloxane
      (PDMS) coating was applied. Peat soil rich in organic matter and with a high
      cation-exchange capacity (CEC), and clay soil low in organic matter and with a
      low CEC were analysed. The influence of these different soil matrices on HS-SPME
      analysis was evaluated by spiking of samples. In general, the recoveries for the
      two spiked soils exceeded 80%. The repeatability of the method was better than
      10%. The limits of detection (LODs) and limits of quantification (LOQs) were in
      the ng S ng(-1) range. The technique may be reliably applied for the
      determination of butyltins and monophenyltin in soils, while it shows some
      limitations for the analysis of di- and triphenyltin (TPhT).

PMID- 16890947
TI  - Adsorption of mixtures of nonionic sugar-based surfactants with other surfactants
      at solid/liquid interfaces II. Adsorption of n-dodecyl-beta-D-maltoside with a
      cationic surfactant and a nonionic ethoxylated surfactant on solids.
AB  - Synergy and antagonism between sugar-based surfactants, a group of
      environmentally benign surfactants, and cationic surfactants and nonionic
      ethoxylated surfactants have been investigated in this study with solids which
      adsorbs only one or other when presented alone. Sugar-based n-dodecyl-beta-D
      maltoside (DM) does not adsorb on silica by itself. However, in mixtures with
      cationic dodecyltrimethylammonium bromide (DTAB) and nonionic nonylphenol
      ethoxylated decyl ether (NP-10), DM adsorbs on silica through hydrophobic
      interactions. In contrast, although DM does adsorb on alumina, the presence of NP
      10 reduces the adsorption of DM as well as that of the total surfactant
      adsorption. Such synergistic/antagonistic effects of sugar-based n-dodecyl-beta-D
      maltoside (DM) in mixtures with other surfactants at solid/liquid interfaces were
      systematically investigated and some general rules on synergy/antagonism in mixed
      surfactant systems are identified. These results have implications for designing
      surfactant combinations for controlled adsorption or prevention of adsorption.

PMID- 16890948
TI  - Scavenging DPPH radicals catalyzed by binary noble metal-dendrimer
      nanocomposites.
AB  - Catalytic activity of gold-platinum, gold-palladium, and platinum-palladium
      dendrimer nanocomposites for scavenging 1,1-diphenyl-2-picrylhydrazyl (DPPH)
      radicals was investigated. The gold-platinum and gold-palladium dendrimer
      nanocomposites were prepared via simultaneous reduction by sodium borohydride in
      the presence of poly(amidoamine) (PAMAM) dendrimers with amine or carboxyl
      terminal groups. The particles were not mixtures of monometallic particles but
      alloyed bimetallic particles. Bimetallic particles exhibited higher catalytic
      activity than monometallic ones.

PMID- 16890949
TI  - Adsorption behavior of propylamine on activated carbon fiber surfaces as induced
      by oxygen functional complexes.
AB  - In this study, the surfaces of activated carbon fibers (ACFs) were modified by
      nitric acid to introduce surface oxygen complexes and to observe the influence of
      those complexes on the propylamine adsorption of the ACFs. It was found that the
      oxygen complexes including carboxylic and phenolic groups were predominantly
      increased, resulting in the increase of total surface acidity. However, the
      specific surface areas and the total pore volumes of the modified ACFs were
      decreased by 5-8% due to the increased blocking (or demolition) of micropores in
      the presence of newly introduced complexes. Despite the decrease of textural
      properties, it was found that the amount of propylamine adsorbed by the modified
      ACFs was increased by approximately 17%. From the XPS results, it was observed
      that propylamine reacted with strong or weak acidic groups, such as COOH or OH,
      on the ACF surfaces, resulting in the formation of pyrrolic-, pyridonic-, or
      pyridine-like structures.

PMID- 16890950
TI  - Surface modification and characterization of indium-tin oxide for organic light
      emitting devices.
AB  - In this work, we used different treatment methods (ultrasonic degreasing,
      hydrochloric acid treatment, and oxygen plasma) to modify the surfaces of indium
      tin oxide (ITO) substrates for organic light-emitting devices. The surface
      properties of treated ITO substrates were studied by atomic force microscopy
      (AFM), X-ray photoelectron spectroscopy (XPS), sheet resistance, contact angle,
      and surface energy measurements. Experimental results show that the ITO surface
      properties are closely related to the treatment methods, and the oxygen plasma is
      more efficient than the other treatments since it brings about smoother surfaces,
      lower sheet resistance, higher work function, and higher surface energy and
      polarity of the ITO substrate. Moreover, polymer light-emitting electrochemical
      cells (PLECs) with differently treated ITO substrates as device electrodes were
      fabricated and characterized. It is found that surface treatments of ITO
      substrates have a certain degree of influence upon the injection current,
      brightness, and efficiency, but hardly upon the turn-on voltages of current
      injection and light emission, which are in agreement with the measured optical
      energy gap of the electroluminescent polymer. The oxygen plasma treatment on the
      ITO substrate yields the best performance of PLECs, due to the improvement of
      interface formation and electrical contact of the ITO substrate with the polymer
      blend in the PLECs.

PMID- 16890951
TI  - TOM20 and the heartbreakers: evidence for the role of mitochondrial transport
      proteins in cardioprotection.

PMID- 16890952
TI  - Viral fitness can influence the repertoire of virus variants selected by
      antibodies.
AB  - Minority genomes in the mutant spectra of viral quasispecies may differ in
      relative fitness. Here, we report experiments designed to evaluate the
      contribution of relative fitness to selection by a neutralizing monoclonal
      antibody (mAb). We have reconstructed a foot-and-mouth disease virus (FMDV)
      quasispecies, with two matched pairs of distinguishable mAb-escape mutants as
      minority genomes of the mutant spectrum. Each mutant of a pair differs from the
      other by 11-fold or 33-fold in relative fitness. Analysis of the mutant spectra
      of virus populations selected with different concentrations of antibody in
      infections in liquid culture medium has documented a dominance of the high
      fitness counterpart in the selected population. Plaque development as a function
      of increasing concentration of the antibody has shown that each mutant of a
      matched pair yielded the same number of plaques, although the high fitness mutant
      required less time for plaque formation, and attained a larger plaque size at any
      given time-point. This result documents equal intrinsic resistance to the
      antibody of each mutant of a matched pair, confirming previous biochemical,
      structural, and genetic studies, which indicated that the epitopes of each mutant
      pair were indistinguishable regarding reactivity with the monoclonal antibody.
      Thus, relative viral fitness can influence in a significant way the repertoire of
      viral mutants selected from a viral quasispecies by a neutralizing antibody. We
      discuss the significance of these results in relation to antibody selection, and
      to other selective forces likely encountered by viral quasispecies in vivo.

PMID- 16890954
TI  - Unwinding of forked DNA structures by UvrD.
AB  - Many studies have demonstrated the need for processing of blocked replication
      forks to underpin genome duplication. UvrD helicase in Escherichia coli has been
      implicated in the processing of damaged replication forks, or the recombination
      intermediates formed from damaged forks. Here we show that UvrD can unwind forked
      DNA structures, in part due to the ability of UvrD to initiate unwinding from
      discontinuities within the phosphodiester backbone of DNA. UvrD does therefore
      have the capacity to target DNA intermediates of replication and recombination.
      Such an activity resulted in unwinding of what would be the parental duplex DNA
      ahead of either a stalled replication fork or a D-loop formed by recombination.
      However, UvrD had a substrate preference for fork structures having a nascent
      lagging strand at the branch point but no leading strand. Furthermore, at such
      structures the polarity of UvrD altered so that unwinding of the lagging strand
      predominated. This reaction is reminiscent of the PriC-Rep pathway of replication
      restart, suggesting that UvrD and Rep may have at least partially redundant
      functions.

PMID- 16890955
TI  - Identification of two interaction sites in SecY that are important for the
      functional interaction with SecA.
AB  - The motor protein SecA drives the translocation of (pre-)proteins across the
      SecYEG channel in the bacterial cytoplasmic membrane by nucleotide-dependent
      cycles of conformational changes often referred to as membrane insertion/de
      insertion. Despite structural data on SecA and an archaeal homolog of SecYEG, the
      identity of the sites of interaction between SecA and SecYEG are unknown. Here,
      we show that SecA can be cross-linked to several residues in cytoplasmic loop 5
      (C5) of SecY, and that SecA directly interacts with a part of transmembrane
      segment 4 (TMS4) of SecY that is buried in the membrane region of SecYEG.
      Mutagenesis of either the conserved Arg357 in C5 or Glu176 in TMS4 interferes
      with the catalytic activity of SecA but not with binding of SecA to SecYEG. Our
      data explain how conformational changes in SecA could be directly coupled to the
      previously proposed opening mechanism of the SecYEG channel.

PMID- 16890956
TI  - The signaling pathway in histidine kinase and the response regulator complex
      revealed by X-ray crystallography and solution scattering.
AB  - The structure of a histidine kinase (ThkA) complexed with a response regulator
      (TrrA) in the two-component regulatory system from hyperthermophile Thermotoga
      maritima was determined by a combination of X-ray crystallography at a resolution
      of 4.2 A and small-angle X-ray scattering (SAXS). The boundary of the three
      component domains (PAS-sensor, dimerization and catalytic domains) of ThkA and
      the bound TrrA molecule were unambiguously assigned in the electron density map
      at 4.2 A resolution. ThkA forms a dimer with crystallographic 2-fold symmetry and
      two monomeric TrrAs bind to the ThkA dimer. SAXS experiments also confirmed this
      association state in solution and specific binding between ThkA and TrrA
      (Kd=8.2x10(-11) M(-2)). The association interface between ThkA and TrrA contains
      the phosphotransfer His residue in the ThkA, indicative of an efficient receipt
      of the phosphoryl group. One Per-Arnt-Sim (PAS) domain does not interact with the
      other PAS domain, but with the catalytic domain of the same polypeptide chain and
      with one TrrA molecule. Observed inter-domain and inter-molecular interactions
      reveal a definite pathway of signal transduction in the kinase/regulator complex.
      In addition, we propose a responsible role of TrrA for the feedback regulation of
      sensing and/or kinase activities of ThkA.

PMID- 16890953
TI  - Topological analysis of plasmid chromatin from yeast and mammalian cells.
AB  - Yeast has proven to be a powerful system for investigation of chromatin
      structure. However, the extent to which yeast chromatin can serve as a model for
      mammalian chromatin is limited by the significant number of differences that have
      been reported. To further investigate the structural relationship between the two
      chromatins, we have performed a DNA topological analysis of pRSSVO, a 5889 base
      pair plasmid that can replicate in either yeast or mammalian cells. When grown in
      mammalian cells, pRSSVO contains an average of 33 negative supercoils, consistent
      with one nucleosome per 181 bp. This is close to the measured nucleosome repeat
      length of 190 bp. However, when grown in yeast cells, pRSSVO contains an average
      of only 23 negative supercoils, which is indicative of only one nucleosome per
      256 bp. This is dramatically different from the measured nucleosome repeat length
      of 165 bp. To account for these observations, we suggest that yeast chromatin is
      composed of relatively short ordered arrays of nucleosomes with a repeat of 165
      bp, separated by substantial gaps, possibly corresponding to regulatory regions.

PMID- 16890957
TI  - Amino-terminal domain stability mediates apolipoprotein E aggregation into
      neurotoxic fibrils.
AB  - The three isoforms of apolipoprotein (apo) E are strongly associated with
      different risks for Alzheimer's disease: apoE4>apoE3>apoE2. Here, we show at
      physiological salt concentrations and pH that native tetramers of apoE form
      soluble aggregates in vitro that bind the amyloid dyes thioflavin T and Congo
      red. However, unlike classic amyloid fibrils, the aggregates adopt an irregular
      protofilament-like morphology and are seemingly highly alpha-helical. The
      aggregates formed at substantially different rates (apoE4>apoE3>apoE2) and were
      significantly more toxic to cultured neuronal cells than the tetramer. Since the
      three isoforms have large differences in conformational stability that can
      influence aggregation and amyloid pathways, we tested the effects of mutations
      that increased or decreased stability. Decreasing the conformational stability of
      the amino-terminal domain of apoE increased aggregation rates and vice versa. Our
      findings provide a new perspective for an isoform-specific pathogenic role for
      apoE aggregation in which differences in the conformational stability of the
      amino-terminal domain mediate neurodegeneration.

PMID- 16890959
TI  - A symmetry of fixation times in evoultionary dynamics.
AB  - In this paper, we show that for evolutionary dynamics between two types that can
      be described by a Moran process, the conditional fixation time of either type is
      the same irrespective of the selective scenario. With frequency dependent
      selection between two strategies A and B of an evolutionary game, regardless of
      whether A dominates B, A and B are best replies to themselves, or A and B are
      best replies to each other, the conditional fixation times of a single A and a
      single B mutant are identical. This does not hold for Wright-Fisher models, nor
      when the mutants start from multiple copies.

PMID- 16890958
TI  - Motor-vehicle boarding and alighting injury--how large a problem?
AB  - The Journal of Safety Research has partnered with the National Center for Injury
      Prevention and Control at the Centers for Disease Control and Prevention (CDC) in
      Atlanta, Georgia, USA, to briefly report on some of the latest findings in the
      research community. This report is the fifth in a series of CDC articles.

PMID- 16890960
TI  - External noise and feedback regulation: steady-state statistics of auto
      regulatory genetic network.
AB  - The steady-state statistics of a single gene auto-regulatory genetic network with
      the additive external Gaussian white noises is investigated. The main result
      shows that the negative feedback will result in that the mRNA noise has a
      positive contribution to the protein noise, but the positive feedback will result
      in that the mRNA noise has a negative contribution to the protein noise. If there
      is no feed back, then the contribution of mRNA noise to protein noise is always
      positive. On the other hand, the analysis and numerical simulations of linear and
      nonlinear feedback show that it is possible that the negative feedback increases,
      but the positive feedback decreases, the protein noise.

PMID- 16890961
TI  - Pseudo amino acid composition and multi-class support vector machines approach
      for conotoxin superfamily classification.
AB  - Conotoxins are disulfide rich small peptides that target a broad spectrum of ion
      channels and neuronal receptors. They offer promising avenues in the treatment of
      chronic pain, epilepsy and cardiovascular diseases. Assignment of newly sequenced
      mature conotoxins into appropriate superfamilies using a computational approach
      could provide valuable preliminary information on the biological and
      pharmacological functions of the toxins. However, creation of protein sequence
      patterns for the reliable identification and classification of new conotoxin
      sequences may not be effective due to the hypervariability of mature toxins. With
      the aim of formulating an in silico approach for the classification of conotoxins
      into superfamilies, we have incorporated the concept of pseudo-amino acid
      composition to represent a peptide in a mathematical framework that includes the
      sequence-order effect along with conventional amino acid composition. The
      polarity index attribute, which encodes information such as residue surface
      buriability, polarity, and hydropathy, was used to store the sequence-order
      effect. Several methods like BLAST, ISort (Intimate Sorting) predictor, least
      Hamming distance algorithm, least Euclidean distance algorithm and multi-class
      support vector machines (SVMs), were explored for superfamily identification. The
      SVMs outperform other methods providing an overall accuracy of 88.1% for all
      correct predictions with generalized squared correlation of 0.75 using jackknife
      cross-validation test for A, M, O and T superfamilies and a negative set
      consisting of short cysteine rich sequences from different eukaryotes having
      diverse functions. The computed sensitivity and specificity for the superfamilies
      were found to be in the range of 84.0-94.1% and 80.0-95.5%, respectively,
      attesting to the efficacy of multi-class SVMs for the successful in silico
      classification of the conotoxins into their superfamilies.

PMID- 16890962
TI  - Estimating trophic link density from quantitative but incomplete diet data.
AB  - The trophic link density and the stability of food webs are thought to be
      related, but the nature of this relation is controversial. This article
      introduces a method for estimating the link density from diet tables which do not
      cover the complete food web and do not resolve all diet items to species level. A
      simple formula for the error of this estimate is derived. Link density is
      determined as a function of a threshold diet fraction below which diet items are
      ignored ("diet partitioning function"). Furthermore, analytic relationships
      between this threshold-dependent link density and the generality distribution of
      food webs are established. A preliminary application of the method to field data
      suggests that empirical results relating link density to diversity might need to
      be revisited.

PMID- 16890963
TI  - Age-associated changes in fat metabolism in the rat and its relation to
      sympathetic activity.
AB  - In this study, to determine if age associated changes in fat metabolism in
      skeletal muscle and liver were related with sympathetic activity, we measured
      sympathetic activity and palmitate oxidation rate, carnitine palmitoyltransferase
      1 (CPT-1) activity, and triglyceride concentration in skeletal muscle and liver
      of rats at 8, 30 and 60 weeks of age. Body weight, intra-abdominal percent of fat
      mass, and plasma level of insulin, leptin, and triglyceride were all
      significantly increased with age. Tissue triglyceride concentration was increased
      with age in liver and skeletal muscle. The palmitate oxidation rate in liver and
      skeletal muscle was reduced with age in rats and inversely correlated with tissue
      triglyceride concentration. CPT-1 activity was not altered with age. Plasma
      catecholamine concentration and sympathetic activity, as measured by spectral
      analysis of heart rate variability, were increased with age. Plasma
      norepinephrine or epinephrine and tissue triglyceride had a positive correlation
      in liver and skeletal muscle. Plasma norepinephrine or epinephrine to tissue
      triglyceride ratio was similar according to age. In summary, in spite of
      increased sympathetic activity with age, the tissue triglyceride concentration
      was increased. Increased sympathetic activity may be the compensatory response
      and the reduced capacity of fatty acid oxidation is a main cause of obesity.

PMID- 16890964
TI  - Glucocorticoid receptors and beta-adrenoceptors in basolateral amygdala modulate
      synaptic plasticity in hippocampal dentate gyrus, but not in area CA1.
AB  - The basolateral amygdala (BLA) is a key structure in a memory-modulatory system
      that regulates stress and stress hormones (glucocorticoid and noradrenaline)
      effects on hippocampal functioning. We have shown previously that priming the
      amygdala differentially affects plasticity in the hippocampal dentate gyrus (DG)
      and CA1, and mimicked acute stress effect on plasticity in these two subregions.
      In the present study, we investigated the mechanisms that mobilize the BLA to
      differentially alter plasticity in DG and CA1. Glucocorticoid receptors
      antagonist RU 38486 or beta-adrenoceptor antagonist propranolol were microinfused
      in the BLA, 10 min prior to BLA activation-induced modulation of long-term
      potentiation (LTP) in DG and CA1. The results showed that neither glucocorticoid
      nor noradrenergic transmissions in the BLA are necessary for LTP induction and
      for the impairing effect of amygdala activation on CA1 LTP. In contrast, blockade
      of glucocorticoid or noradrenergic transmission in BLA, increased baseline
      synaptic transmission in the DG, but suppressed the enhancing effect of BLA
      activation on DG LTP. These findings provide further evidence for a differential
      amygdala control of hippocampal subregions as well as for differential memory
      processes involving CA1 and DG. They also provide insight into how stress
      hormones exert their actions on the circuits involved in these processes.

PMID- 16890965
TI  - Constitutive endocytosis of the metabotropic glutamate receptor mGluR7 is
      clathrin-independent.
AB  - Metabotropic glutamate receptors (mGluRs) are G protein-coupled receptors (GPCRs)
      that are widely expressed throughout the brain and are involved in synaptic
      development, transmission, and plasticity. The endocytosis of several members of
      the GPCR superfamily of receptors, such as beta-adrenergic receptors, has been
      studied extensively. In contrast, the mechanisms regulating mGluR endocytosis and
      intracellular trafficking remain poorly defined. We describe here for the first
      time a distinct endocytic and intracellular sorting pathway utilized by mGluR7.
      We show that mGluR7 constitutively internalizes via a non-clathrin mediated
      pathway in heterologous cells and in neurons. Unlike clathrin-mediated NMDAR
      endocytosis, mGluR7 traffics via an Arf6-positive endosomal pathway, similar to
      other well-characterized proteins such as major histocompatibility complex class
      I (MHC I) and the GPI-anchored protein CD59. Thus constitutive endocytosis of
      mGluR7 in neurons is not regulated by clathrin-dependent mechanisms, and this
      clathrin-independent pathway ultimately determines the amount of receptor present
      on the plasma membrane available to bind and respond to glutamate.

PMID- 16890966
TI  - Hepatic-portal oleic acid inhibits feeding more potently than hepatic-portal
      caprylic acid in rats.
AB  - In several human and animal studies, medium-chain triglycerides decreased food
      intake more than did long-chain triglycerides. It is possible that faster uptake
      and metabolism of medium-chain fatty acids in the liver is responsible for this
      difference. To test this hypothesis we compared the feeding effects of hepatic
      portal vein (HPV) infusion of the medium-chain fatty acid caprylic acid (CA) with
      those of the long-chain fatty acid oleic acid (OA). Contrary to our expectation,
      six-h HPV infusion of 14 microg/min (50 nmol/min) OA robustly inhibited feeding,
      whereas infusion of 22 or 220 microg/min (150 and 1500 nmol/min) CA failed to
      have any effect on feeding. Only a much larger dose of CA, 1100 microg/min (7500
      nmol/min) inhibited feeding similarly to 14 microg/min OA. The increased feeding
      inhibitory potency of OA did not appear to be due to differences in stimulation
      of hepatic fatty acid oxidation because equimolar (50 nmol/min) doses of OA (14
      microg/min) and CA (7 microg/min) did not differentially affect post-infusion
      levels of beta-hydroxybutyrate. Stress, inflammation, acute hepatotoxicity or
      oxidative stress also do not appear to account for the increased feeding
      inhibitory potency of HPV OA because plasma concentrations of the stress hormones
      corticosterone and epinephrine, the pro-inflammatory cytokines interleukin-6 and
      tumor necrosis factor-alpha, the liver enzymes gamma-glutamyl transferase and
      alanine aminotransferase and as well as hepatic levels of malondialdehyde and
      glutathione were all similar after HPV infusion of saline or of 50 nmol/min OA or
      CA.

PMID- 16890967
TI  - Biosynthesis of curcuminoids and gingerols in turmeric (Curcuma longa) and ginger
      (Zingiber officinale): identification of curcuminoid synthase and
      hydroxycinnamoyl-CoA thioesterases.
AB  - Members of the Zingiberaceae such as turmeric (Curcuma longa L.) and ginger
      (Zingiber officinale Rosc.) accumulate at high levels in their rhizomes important
      pharmacologically active metabolites that appear to be derived from the
      phenylpropanoid pathway. In ginger, these compounds are the gingerols; in
      turmeric these are the curcuminoids. Despite their importance, little is known
      about the biosynthesis of these compounds. This investigation describes the
      identification of enzymes in the biosynthetic pathway leading to the production
      of these bioactive natural products. Assays for enzymes in the phenylpropanoid
      pathway identified the corresponding enzyme activities in protein crude extracts
      from leaf, shoot and rhizome tissues from ginger and turmeric. These enzymes
      included phenylalanine ammonia lyase, polyketide synthases, p-coumaroyl shikimate
      transferase, p-coumaroyl quinate transferase, caffeic acid O-methyltransferase,
      and caffeoyl-CoA O-methyltransferase, which were evaluated because of their
      potential roles in controlling production of certain classes of gingerols and
      curcuminoids. All crude extracts possessed activity for all of these enzymes,
      with the exception of polyketide synthases. The results of polyketide synthase
      assays showed detectable curcuminoid synthase activity in the extracts from
      turmeric with the highest activity found in extracts from leaves. However, no
      gingerol synthase activity could be identified. This result was explained by the
      identification of thioesterase activities that cleaved phenylpropanoid pathway
      CoA esters, and which were found to be present at high levels in all tissues,
      especially in ginger tissues. These activities may shunt phenylpropanoid pathway
      intermediates away from the production of curcuminoids and gingerols, thereby
      potentially playing a regulatory role in the biosynthesis of these compounds.

PMID- 16890969
TI  - An insight into burns in a developing country: a Sri Lankan experience.
AB  - Burn injuries represent a diverse and varied challenge to medical and paramedical
      staff. The management of burns and their sequelae in a well-equipped, modern
      burns unit remains demanding despite advances in surgical techniques and
      development of tissue-engineered biomaterials; in a developing country, these
      difficulties are amplified many times. Sri Lanka has a high incidence of burn
      related injuries annually due to a combination of adverse social, economic and
      cultural factors. The management of burn injuries remains a formidable public
      health problem. The epidemiology of burns, challenges faced in their management
      and effective strategies specific to Sri Lanka, such as the Safe Bottle Lamp
      campaign, are highlighted in this paper.

PMID- 16890968
TI  - Antiprotozoal and cytotoxic naphthalene derivatives from Diospyros assimilis.
AB  - Chemical investigation of the roots of Diospyros assimilis had led to the
      isolation and characterization of six naphthalene derivatives, two 2
      naphthaldehyes, namely 4-hydroxy-3,5-dimethoxy-2-naphthaldehyde 1, 4-hydroxy-5
      methoxy-2-naphthaldehye 2, its related isomer 5-hydroxy-4-methoxy-2
      naphthaldehyde 3 and three commonly occurring naphthoquinones, diospyrin 4, 8'
      hydroxyisodiospyrin 5 and the simple monomer, plumbagin 6. Their chemical
      structures were established by detailed NMR investigations including 1H and 13C
      NMR, HSQC, HMBC and NOESY experiments. In addition, the naphthalene derivatives 1
      5 were evaluated for their in vitro antiprotozoal activity against protozoan
      parasites belonging to the genera Trypanosoma, Leishmania and Plasmodium. Among
      the tested compounds, naphthaldehyde 1 showed moderate inhibition of the growth
      of the parasites, T. brucei, T. cruzi, L. donovani with IC50 values of 19.82,
      12.28 and 38.78 microM and displayed cytotoxicity towards rat skeletal myoblasts
      (L-6 cells) with IC50 of 174.94 microM, while 2 and 3 were found to be
      comparatively less active to 1. The dimeric quinones 4 and 5 exhibited good
      activity against T. brucei and L. donovani with IC50 of 1.12 and 8.82 microM and
      12.94 and 16.66 microM respectively.

PMID- 16890970
TI  - A note on the accuracy of PAC-likelihood inference with microsatellite data.
AB  - Stephens and Donnelly have introduced a simple yet powerful importance sampling
      scheme for computing the likelihood in population genetic models. Fundamental to
      the method is an approximation to the conditional probability of the allelic type
      of an additional gene, given those currently in the sample. As noted by Li and
      Stephens, the product of these conditional probabilities for a sequence of draws
      that gives the frequency of allelic types in a sample is an approximation to the
      likelihood, and can be used directly in inference. The aim of this note is to
      demonstrate the high level of accuracy of "product of approximate conditionals"
      (PAC) likelihood when used with microsatellite data. Results obtained on
      simulated microsatellite data show that this strategy leads to a negligible bias
      over a wide range of the scaled mutation parameter theta. Furthermore, the
      sampling variance of likelihood estimates as well as the computation time are
      lower than that obtained with importance sampling on the whole range of theta. It
      follows that this approach represents an efficient substitute to IS algorithms in
      computer intensive (e.g. MCMC) inference methods in population genetics.

PMID- 16890971
TI  - Is it true that ozone is always toxic? The end of a dogma.
AB  - There are a number of good experimental studies showing that exposure by
      inhalation to prolonged tropospheric ozone damages the respiratory system and
      extrapulmonary organs. The skin, if extensively exposed, may also contribute to
      the damage. The undoubtful strong reactivity of ozone has contributed to
      establish the dogma that ozone is always toxic and its medical application must
      be proscribed. Although it is less known, judiciously practiced ozonetherapy is
      becoming very useful either on its own or applied in combination with orthodox
      medicine in a broad range of pathologies. The opponents of ozonetherapy base
      their judgment on the ozone chemistry, and physicians, without any knowledge of
      the problem, are often skeptical. During the last 15 years, a clear understanding
      of the action of ozone in biology and medicine has been gained, allowing today to
      argue if it is true that ozone is always toxic. The fundamental points that are
      discussed in this paper are: the topography, anatomical and biochemical
      characteristics of the organs daily exposed to ozone versus the potent
      antioxidant capacity of blood exposed to a small and precisely calculated dose of
      ozone only for a few minutes. It is becoming clear how the respiratory system
      undergoing a chronic oxidative stress can release slowly, but steadily, a huge
      amount of toxic compounds able to enter the circulation and cause serious damage.
      The aim of this paper is to objectively evaluate this controversial issue.

PMID- 16890972
TI  - 15-deoxy-Delta12,14-prostaglandin J2 induces renal epithelial cell death through
      NF-kappaB-dependent and MAPK-independent mechanism.
AB  - The peroxisome proliferator-activated receptor-gamma (PPARgamma) ligand 15d-PGJ2
      induces cell death in renal proximal tubular cells. However, the underlying
      molecular mechanism(s) remains unidentified. The present study was undertaken to
      examine the roles of reactive oxygen species (ROS), mitogen-activated protein
      kinase, and NF-kappaB in opossum kidney (OK) cell death induced by 15d-PGJ2.
      Treatment of OK cells with 15d-PGJ2 resulted in a concentration- and time
      dependent cell death, which was largely attributed to apoptosis. 15d-PGJ2
      increased ROS production and the effect was inhibited by catalase and N
      acetylcysteine. The 15d-PGJ2-induced cell death was also prevented by these
      antioxidants, suggesting that the cell death was associated with ROS generation.
      The PPARgamma antagonist GW9662 did not prevent the 15d-PGJ2-induced cell death.
      15d-PGJ2 caused a transient activation of extracellular signal-regulated kinase
      (ERK). However, inhibitors (PD98059 and U0126) of MEK, an ERK upstream kinase,
      did not alter the 15d-PGJ2-induced cell death. Transfection with constitutively
      active MEK and dominant-negative MEK had no effect on the cell death. 15d-PGJ2
      inhibited the NF-kappaB transcriptional activity, which was accompanied by an
      inhibition of nuclear translocation of the NF-kappaB subunit p65 and impairment
      in DNA binding. Inhibition of NF-kappaB with a NF-kappaB specific inhibitor
      pyrrolidinecarbodithioate and transfection with IkappaBalpha (S32A/36A) caused
      cell death. These results suggest that the 5d-PGJ2-induced OK cell death was
      associated with ROS production and NF-kappaB inhibition, but not with MAPK
      activation.

PMID- 16890974
TI  - Production of antibodies against microcystin-RR for the assessment of purified
      microcystins and cyanobacterial environmental samples.
AB  - Microcystins (MC) are cyanobacterial hepatotoxins responsible for animal
      poisoning and human health incidents. Immunoassays provide a sensitive means to
      detect these toxins, although cross-reactivity characteristics of different
      antibodies are variable, and most antibodies have been produced against MC-LR.
      Here, we have produced the first polyclonal antibodies against the commonly
      occurring variant, MC-RR, and compared them with MC-LR antibodies for the
      analysis of purified MCs and cyanobacterial environmental samples. Both antisera
      cross-reacted with all MCs tested, and with the related cyanobacterial
      hepatotoxin nodularin-R, but not with non-toxic cyanobacterial peptides. In
      general, better cross-reactivity characteristics were observed with the MC-RR
      antisera and limits of quantification were lower for most variants, with all MCs
      tested and nodularin-R having limits of quantification of 0.31 nM or below. The
      antisera had different affinities to mixtures containing pooled MC-LR and MC-RR,
      with MC-LR antisera underestimating total MC concentration when MC-RR represented
      over 70% of the total MC pool. Both antisera correlated well with HPLC-UV data
      when incorporated into ELISAs to screen previously characterised environmental
      samples from Aland, Finland. MC-RR antisera are useful for screening samples
      containing multiple MCs, and particularly for samples primarily containing MC-RR
      variants.

PMID- 16890973
TI  - Equine laminitis: bites by Bothrops spp cause hoof lamellar pathology in the
      contralateral as well as in the bitten limb.
AB  - The envenoming caused by Bothrops snakebite includes local symptoms, such as
      pronounced edema, hemorrhage, intense pain, vesicles, blisters and myonecrosis.
      The principal systemic symptom consists in the alteration of blood clotting, due
      to fibrinogen consumption and platelet abnormalities. The horses involved in this
      study had this symptomatology and one of them exhibited symptoms consistent with
      laminitis in the bitten and in the contralateral limbs. Laminitis lesions were
      characterized by separation of the hoof lamellar basement membrane (BM) from
      basal cells of the epidermis. These results demonstrated that Bothrops snake
      venom can induce acute laminitis. We conclude that components of the venom,
      probably metalloproteinases, cause severe lesions in the hoof early in the
      envenoming process. Antivenom therapy must be initiated as soon as possible in
      order to prevent complications, not only to save the life of an envenomed horse,
      but also to avoid the dysfunctional sequels of laminitis.

PMID- 16890975
TI  - Degradation of phenolic compounds with hydrogen peroxide catalyzed by enzyme from
      Serratia marcescens AB 90027.
AB  - In this paper, the degradation of phenolic compounds using hydrogen peroxide as
      oxidizer and the enzyme extract from Serratia marcescens AB 90027 as catalyst was
      reported. With such an enzyme/H2O2 combination treatment, a high chemical oxygen
      demand (COD) removal efficiency was achieved, e.g., degradation of hydroquinone
      exceeded 96%. From UV-visible and IR spectra, the degradation mechanisms were
      judged as a process of phenyl ring cleavage. HPLC analysis shows that in the
      degradation p-benzoquinone, maleic acid and oxalic acid were formed as
      intermediates and that they were ultimately converted to CO2 and H2O. With the
      enzyme/H2O2 treatment, vanillin, hydroquinone, catechol, o-aminophenol, p
      aminophenol, phloroglucinol and p-hydroxybenzaldehyde were readily degraded,
      whereas the degradation of phenol, salicylic acid, resorcinol, p-cholorophenol
      and p-nitrophenol were limited. Their degradability was closely related to the
      properties and positions of their side chain groups. Electron-donating groups,
      such as -OH, -NH2 and -OCH3 enhanced the degradation, whereas electron
      withdrawing groups, such as -NO2, -Cl and -COOH, had a negative effect on the
      degradation of these compounds in the presence of enzyme/H2O2. Compounds with -OH
      at ortho and para positions were more readily degraded than those with -OH at
      meta positions.

PMID- 16890976
TI  - Rheological and fractal characteristics of granular sludge in an upflow anaerobic
      reactor.
AB  - The rheological and fractal characteristics of the granular sludge in an upflow
      anaerobic sludge blanket (UASB) reactor were investigated in this study. The
      influences of sludge concentration and temperature on the rheological properties
      of the granular sludge were evaluated, and the Bingham model was adopted to
      describe its rheology. In addition, image analysis was used to determine the
      sludge fractal dimension. The results indicate that the UASB granular sludge
      showed a shear-thinning behavior. The relationships between the limiting
      viscosity and the sludge concentration, as well as the limiting viscosity and
      temperature could be respectively modeled using an exponential equation and
      Arrhenius equation well. The Bingham model was able to adequately describe the
      rheology of the granular sludge. The fractal dimension of the granular sludge,
      2.79+/-0.03, was larger than that of some other aggregates, suggesting that the
      granular sludge were more compact and denser. Furthermore, the relationship
      between rheological and fractal properties of the granular sludge could be
      properly described with the model proposed by Shih et al. [1990. Scaling behavior
      of the elastic properties of colloidal. Phys. Rev. A 42, 4772-4779].

PMID- 16890977
TI  - Role of biological activity and biomass distribution in air biofilter
      performance.
AB  - The effects of temporal and spatial changes in biological activity and biomass
      amount on biofilter performance were investigated in a lab-scale trickle-bed air
      biofilter at a toluene loading of 46.9gm(-3)h(-1) under two different
      experimental strategies, namely, periodic backwashing at a rate of 1h once a week
      and 2d starvation. Analysis of the overall reaction for toluene metabolism
      revealed that cell synthesis was relatively favored over toluene oxidation in the
      inlet section of the biofilter, but over time its oxidation became favored
      throughout the biofilter bed. Periodic in situ backwashing with media
      fluidization effectively made even spatial distribution of biomass along the bed
      media, by which consistent high removal performance in the biofilter has been
      attained. After 2d starvation, the ratio of the biofilm EPS to the total biomass
      increased along the media bed depth, while the total biomass in the media bed
      subsequently decreased. The presence of sufficient biomass and microbial activity
      favorably influenced biofilter reacclimation after restart-up following
      starvation.

PMID- 16890978
TI  - Effect of UV-B exposure on eggs and embryos of patagonian anurans and evidence of
      photoprotection.
AB  - In Patagonia, enhanced levels of ultraviolet radiation (UVR) are affecting not
      only the southernmost territories but the northern as well, and there is a
      growing body of evidence indicating effects on terrestrial and aquatic
      communities. Anurans occur along a wide geographical gradient in Patagonia and
      are common in shallow waters, usually breeding during spring when seasonal UV-B
      radiation is at its highest level. In this paper we analyse the effective
      irradiances (I) experienced in nature by eggs and embryos of the patagonian
      anurans Pleurodema bufoninum, Pleurodema thaul and Bufo spinulosus papillosus,
      considering water and egg jelly optical properties. Besides, we determine
      photoprotective pigments in eggs and embryos of the different species, and
      ontogenetic shifts in pigment concentration. Finally, we studied the effects of
      natural and enhanced levels of UV-B on eggs of P. bufoninum aiming to evaluate
      the role of the jelly envelope in screening the damaging radiation. The evidence
      gathered in this work shows that natural and enhanced UV-B levels did not induce
      significant changes on the survivorship but incremented the occurrence of
      malformations. Also, the species experiencing high levels of exposure presented
      high concentrations of melanin suggesting that exposure to sunlight triggers
      photoprotection by pigments. Collectively our results suggest that the studied
      species bear certain levels of adaptation to cope with high ambient UVR conferred
      by environmental and biological factors.

PMID- 16890979
TI  - Human exposure to polychlorinated naphthalenes through the consumption of edible
      marine species.
AB  - The concentrations of polychlorinated naphthalenes (PCNs) were determined in
      samples of 14 edible marine species (sardine, tuna, anchovy, mackerel, swordfish,
      salmon, hake, red mullet, sole, cuttlefish, squid, clam, mussel and shrimp),
      which are widely consumed by the population of Catalonia, Spain. The daily intake
      of PCNs associated with this consumption was also determined. A total of 42
      composite samples were analyzed by HRGC/HRMS. The highest PCN levels (ng/kg of
      fresh weight) were found in salmon (227) followed by mackerel (95) and red mullet
      (68), while the lowest levels of total PCNs corresponded to shrimp (4.9) and
      cuttlefish (2.7). With the exception of cephalopods and shellfish species, in
      which tetra-CN was the predominant homologue, penta-CN (60%) was the predominant
      contributor to total PCNs. For a standard male adult, PCN intake through the
      consumption of edible marine species was 1.53 ng/day. The highest contributions
      to this intake (ng/day) corresponded to salmon (0.41), sole (0.28) and tuna
      (0.24). Concerning health risks, species-specific TEFs such as those reported by
      WHO and NATO for PCDD/Fs and dioxin-like PCBs are not currently available for PCN
      congeners. Although in general terms the results of the present study do not seem
      to suggest specific risks derived from exposure to PCNs through fish and seafood
      consumption, to establish the contribution of individual PCN congeners to total
      TEQ is clearly necessary for the assessment of human health risks.

PMID- 16890980
TI  - A role for mitotic recombination in leukemogenesis.

PMID- 16890982
TI  - Stage 1A squamous cell carcinoma of the vulva.

PMID- 16890981
TI  - Early clinical outcomes of 3D-conformal radiotherapy using accelerated
      hyperfractionation without intracavitary brachytherapy for cervical cancer.
AB  - PURPOSE/OBJECTIVE: To evaluate the outcome of cervical cancer patients unable to
      undergo conventional intracavitary brachytherapy (ICBT) treated with 3D-conformal
      radiotherapy (3DCRT) alone using accelerated hyperfractionation (AHF). METHODS
      AND MATERIALS: We reviewed the records of 7 patients who had received definitive
      radiotherapy with 3DCRT alone using AHF for cervical cancer between 2002 and
      2005. FIGO stage was IB (1), IIB (2), IIIA (1), IIIB (2), and IVA (1). The reason
      we did not perform ICBT was due to patient refusal. In 1 patient with stage IB, a
      total dose of 65.4 Gy was delivered by local irradiation (LI) only. In 1 patient
      with stage IIIA, a total dose of 60 Gy was delivered by LI only. In 5 patients
      with Stage IIB-IV, a median total dose of 70.8 Gy was delivered by combination of
      whole pelvic irradiation (median dose of 45 Gy) with LI. Median overall treatment
      time was 42 days. RESULTS: Median follow-up for survival patients was 17 months.
      Out of 7 patients, 6 patients had CR and 1 patient had PR. The response rate was
      100%. The 2-year local control rate was 85.7%. Of these patients, 5 are alive
      without disease and 1 is alive with lung metastasis. CONCLUSIONS: Our outcomes
      suggest that 3DCRT using AHF may be a promising as a definitive treatment for
      cervical cancer when ICBT is not able to be performed.

PMID- 16890983
TI  - Inhibition of TEGDMA and HEMA-induced genotoxicity and cell cycle arrest by N
      acetylcysteine.
AB  - OBJECTIVES: Dental resin monomers like triethylene glycol dimethacrylate (TEGDMA)
      and 2-hydroxyethyl methacrylate (HEMA) are able to cause an imbalance of the
      redox state in mammalian cells. The resulting oxidative stress originating from
      reactive oxygen species (ROS) has been associated with cytotoxicity. We
      hypothesized that ROS might contribute to the generation of genotoxicity by
      TEGDMA and HEMA as well. Therefore, we examined the formation of micronuclei in
      V79 cells by both resin monomers in the presence of the antioxidant N
      acetylcysteine (NAC), which scavenges ROS. In addition, we analyzed the effects
      of TEGDMA and HEMA on the normal cell cycle in the presence of NAC. METHODS: V79
      fibroblasts were exposed to increasing concentrations of TEGDMA and HEMA in the
      presence and absence of NAC for 24h. Genotoxicity was indicated by the formation
      of micronuclei. The modification of the normal cell cycle was analyzed by flow
      cytometry (FACS). RESULTS: A dose-related increase in the number of micronuclei
      in V79 cells-induced by TEGDMA and HEMA indicated genotoxicity of both chemicals.
      However, the formation of micronuclei was reduced in the presence of 10 mmol/L
      NAC, indicating its protective role. A cell cycle delay in G2 phase caused by
      TEGDMA was absent when cells were co-treated with NAC. Similarly, the presence of
      NAC led to a reversion of the cell cycle delay in HEMA-treated cell cultures.
      SIGNIFICANCE: Our results suggest that genotoxic effects and the modification of
      the cell cycle caused by TEGDMA and HEMA are mediated, at least in part, by
      oxidative stress.

PMID- 16890984
TI  - Fracture toughness determination of two dental porcelains with the indentation
      strength in bending method.
AB  - OBJECTIVE: This study was to investigate the influence of the bending test
      configurations and the crosshead displacement speeds on the fracture toughness
      (K(Ic)) of dental porcelains obtained with the indentation strength in bending
      (ISB) method. METHODS: The strength of the dental veneering porcelains Duceram
      and Sintagon Zx, Vickers' indented at a load of 2 kg was measured at a crosshead
      speed of 0.5mm/min with three test configurations, which were 3-point, 4-point,
      and biaxial bending. Two more groups of Sintagon Zx were tested the same way, but
      at speeds of 0.1, and 0.05 mm/min, respectively. Both porcelains, the three
      crosshead speeds, and the three test configurations were compared statistically.
      RESULTS: Duceram had a higher toughness than Sintagon Zx with all three test
      configurations and there was no significant difference between three test
      configurations with either porcelain. Within the crosshead speed groups of
      Sintagon Zx, a significant difference was found only in the 0.5mm/min group
      between the 3-point, and 4-point configurations. Within the configuration groups,
      significant differences were found between all speeds with the 3-point
      configuration and only between the highest and lowest speed with the 4-point and
      the biaxial tests. CONCLUSION: The crosshead displacement speed can cause
      statistically different results of fracture toughness obtained with the ISB
      method.

PMID- 16890985
TI  - Nanoindentation derived stress-strain properties of dental materials.
AB  - OBJECTIVES: The aim of the study is to investigate the stress-strain response of
      different dental materials, especially dental brittle materials, and compare them
      with enamel. METHODS: A nano-based indentation system (Ultra Micro-Indentation
      System, UMIS-2000, CSIRO, Australia) was used to determine the indentation stress
      strain response of two kinds of dental ceramics (Cerec 2 Mark II and Vita VM9),
      one kind of dental alloy (Wiron 99) and healthy enamel. A spherical indenter was
      used to test the materials with nanometer and micro-Newton displacement and force
      resolution. Assuming the elastic modulus remained constant, a plot of contact
      pressure versus contact strain, H-a/R, of each material was obtained. RESULTS: By
      comparing the H-a/R curve of the different materials with enamel, it can be
      concluded that only the metallic alloy, has similar stress-strain response as
      enamel. Dental ceramics showed much higher yield stress response than enamel.
      VM9, a porcelain veneer component of crown/bridge structure, is slightly softer
      than its core, Mark II. The yield point for Mark II and VM9 are nearly 10 and
      7GPa, respectively, and approximately 2GPa for Wiron alloy and enamel.
      SIGNIFICANCE: H-a/R curves provide a new method to compare the mechanical
      properties of different dental materials. From the standpoint of structural
      reliability, strong and tough materials with primarily elastic response, such as
      toughened ceramics are required to enable dental crown/bridges to have long term
      reliability. On the other hand, materials with too high hardness or yield
      response may damage opposing teeth during occlusal contact. Future studies may
      establish a relationship between stress and strain property and abrasive wear of
      dental material.

PMID- 16890986
TI  - Comparison of two methods for measuring the polymerization characteristics of
      flowable resin composites.
AB  - OBJECTIVES: The purpose of this study was to compare two methods for assessing
      the polymerization characteristics of flowable resin composites. METHODS: Two
      different flowable resin composites and a hybrid resin composite control were
      investigated. In order to measure the volumetric shrinkage (DeltaV), each
      material was placed into a mould and extruded into a water-filled dilatometer.
      The specimens were then light irradiated for 30s using a curing unit with the
      power density adjusted to either 100 or 600mW/cm(2). For the speckle contrast
      measurement, each resin composite was condensed into a glass tube and irradiated.
      The laser-speckle field was recorded in a digital frame. The calculated values
      were obtained for each pair of adjacent patterns and the changes in speckle
      contrast as a function of time were obtained. RESULTS: The average DeltaV values
      of the resins after 180s ranged from approximately 3.3 to 4.4% for the flowable
      composites and from approximately 1.8 to 2.3% for the hybrid composite control.
      The overall magnitude of the speckle contrasts decreased soon after the initial
      light exposure commenced and gradually increased thereafter. The speckle contrast
      measurements revealed changes in the pastes due to the polymerization of the
      flowable resins that were greater than those obtained with the water-filled
      dilatometer. SIGNIFICANCE: These data suggest that the polymerization
      characteristics of flowable resins can be measured successfully using two
      different methods. Moreover, our findings are of clinical relevance, as the data
      obtained under laboratory conditions might give an indication of the suitability
      of flowable resin composites for specific clinical applications.

PMID- 16890987
TI  - Kinetics of inhibition of ribonuclease A by Pholiota Nameko polysaccharide.
AB  - Pholiota nameko polysaccharide (PNPS-1) has been isolated and purified by enzyme
      hydrolysis, hot water extraction, ethanol precipitation, ion-exchange
      chromatography and gel-filtration column chromatography. The inhibition of bovine
      pancreas ribonuclease (RNase A) by PNPS-1 has been studied to elucidate the
      mechanism responsible for the decreased activity. PNPS-1 was effective in a
      linear mixed-type inhibition as suggested from the Lineweaver-Burk plot, Dixon
      plot and their replots. The values of K(i) and alphaK(i) were estimated as 299.92
      and 545.71 microM, respectively. The alphaK(i) was greater than K(i) indicating
      that noncompetitive inhibition was predominant over competitive inhibition.

PMID- 16890988
TI  - Stem cell-based tissue engineering with silk biomaterials.
AB  - Silks are naturally occurring polymers that have been used clinically as sutures
      for centuries. When naturally extruded from insects or worms, silk is composed of
      a filament core protein, termed fibroin, and a glue-like coating consisting of
      sericin proteins. In recent years, silk fibroin has been increasingly studied for
      new biomedical applications due to the biocompatibility, slow degradability and
      remarkable mechanical properties of the material. In addition, the ability to now
      control molecular structure and morphology through versatile processability and
      surface modification options have expanded the utility for this protein in a
      range of biomaterial and tissue-engineering applications. Silk fibroin in various
      formats (films, fibers, nets, meshes, membranes, yarns, and sponges) has been
      shown to support stem cell adhesion, proliferation, and differentiation in vitro
      and promote tissue repair in vivo. In particular, stem cell-based tissue
      engineering using 3D silk fibroin scaffolds has expanded the use of silk-based
      biomaterials as promising scaffolds for engineering a range of skeletal tissues
      like bone, ligament, and cartilage, as well as connective tissues like skin. To
      date fibroin from Bombyx mori silkworm has been the dominant source for silk
      based biomaterials studied. However, silk fibroins from spiders and those formed
      via genetic engineering or the modification of native silk fibroin sequence
      chemistries are beginning to provide new options to further expand the utility of
      silk fibroin-based materials for medical applications.

PMID- 16890989
TI  - Synthesis and in vitro anti-cancer evaluation of tamoxifen-loaded magnetite/PLLA
      composite nanoparticles.
AB  - The present study deals with the synthesis and characterization of tamoxifen
      loaded magnetite/poly(l-lactic acid) composite nanoparticles (TMCN), and their in
      vitro anti-cancer activity against MCF-7 breast cancer cells. The composite
      nanoparticles with an average size of approximately 200 nm, were synthesized via
      a solvent evaporation/extraction technique in an oil/water emulsion. The
      superparamagnetic property (saturation magnetization value of approximately 7
      emu/g) of the TMCN is provided by Fe(3)O(4) nanoparticles of approximately 6 nm
      encapsulated in the poly(l-lactic acid) matrix. The encapsulation efficiency of
      the Fe(3)O(4) and tamoxifen as a function of the concentration in the organic
      phase was investigated. The uptake of TMCN and tamoxifen by MCF-7 was estimated
      from the intracellular iron concentration. After 4h incubation of MCF-7 with
      TMCN, significant changes in the cell morphology were discernible from phase
      contrast microscopy. Cytotoxicity assay shows that while the Fe(3)O(4)-loaded
      poly(l-lactic acid) composite nanoparticles exhibit no significant cytotoxicity
      against MCF-7, approximately 80% of the these cells were killed after incubation
      for 4 days with TMCN.

PMID- 16890991
TI  - Vibrio vulnificus and V. parahaemolyticus necrotising fasciitis in fishermen
      visiting an estuarine tropical northern Australian location.
AB  - Three cases of severe necrotising fasciitis due to Vibrio vulnificus (two cases)
      and Vibrio parahaemolyticus (one case, fatal), have occurred in Caucasian
      tourists while fishing at a remote tropical northern Australian estuarine area.
      Infections were acquired over a 4-year period during the tourist fishing season
      (April to July 2000-2003), when water temperatures range from 23 to 30 degrees C.
      They are notable for their geographical clustering in the remote western aspect
      of the Gulf of Carpentaria, an area characterised by sedimentary stratiform zinc
      lead-silver deposits and a major mining operation. Patients presented with
      classical bullous cellulitis with necrotising fasciitis, accompanied by severe
      sepsis. Underlying risk factors were identified in each patient; in one instance,
      previously unrecognised haemochromatosis was diagnosed. Likely reasons for Vibrio
      occurrence in this particular ecological niche are discussed.

PMID- 16890990
TI  - Advances in white matter imaging: a review of in vivo magnetic resonance
      methodologies and their applicability to the study of development and aging.
AB  - Several newer magnetic resonance imaging (MRI) techniques are increasingly being
      applied to the study of white matter development and pathology across the
      lifespan. These techniques go beyond traditional macrostructural volumetric
      methods and provide valuable information about underlying tissue integrity and
      organization at the microstructural and biochemical levels. We first provide an
      overview of white matter development and discuss the role of white matter and
      myelin in cognitive function. We also review available studies of development
      that have employed traditional volumetric measures. Then, we discuss the
      contributions of four newer imaging paradigms to our understanding of brain
      development and aging. These paradigms are Diffusion Tensor Imaging (DTI),
      Magnetization Transfer Imaging (MTI), T2-Relaxography, and Magnetic Resonance
      Spectroscopy (MRS). Studies examining brain development during childhood and
      adulthood as well as studies of the effects of aging are discussed.

PMID- 16890992
TI  - The physiological and pathophysiological roles of neuronal histamine: an insight
      from human positron emission tomography studies.
AB  - Histamine neurons are exclusively located in the posterior hypothalamus, and
      project their fibers to almost all regions of the human brain. Although a
      significant amount of research has been done to clarify the functions of the
      histaminergic neuron system in animals, a few studies have been reported on the
      roles of this system in the human brain. In past studies, we have been able to
      clarify some of the functions of histamine neurons using different methods, such
      as histamine-related gene knockout mice or human positron emission tomography
      (PET). The histaminergic neuron system is known to modulate wakefulness, the
      sleep-wake cycle, appetite control, learning, memory and emotion. Accordingly we
      have proposed that histamine neurons have a dual effect on the CNS, with both
      stimulatory and suppressive actions. As a stimulator, neuronal histamine is one
      of the most important systems that stimulate and maintain wakefulness. Brain
      histamine also functions as a suppressor in bioprotection against various noxious
      and unfavorable stimuli of convulsion, drug sensitization, denervation
      supersensitivity, ischemic lesions and stress susceptibility. This review
      summarizes our works on the functions of histamine neurons using human PET
      studies, including the development of radiolabeled tracers for histamine H1
      receptors (H1R: (11)C-doxepin and (11)C-pyrilamine), PET measurements of H1R in
      depression, schizophrenia, and Alzheimer's disease (AD), and studies on the
      sedative effects of antihistamines using H(2)(15)O and H1R occupancy in the human
      brain. These molecular and functional PET studies in humans are useful for drug
      development in this millennium.

PMID- 16890993
TI  - Computation of gaze orientation under unrestrained head movements.
AB  - Given the high relevance of visual input to human behavior, it is often important
      to precisely monitor the spatial orientation of the visual axis. One popular and
      accurate technique for measuring gaze orientation is based on the dual search
      coil. This technique does not allow for very large displacements of the subject,
      however, and is not robust with respect to translations of the head. More
      recently, less invasive procedures have been developed that record eye movements
      with camera-based systems attached to a helmet worn by the subject. Computational
      algorithms have also been developed that can calibrate eye orientation when the
      head's position is fixed. Given that camera-based systems measure the eye's
      position in its orbit, however, the reconstruction of gaze orientation is not as
      straightforward when the head is allowed to move. In this paper, we propose a new
      algorithm and calibration method to compute gaze orientation under unrestrained
      head conditions. Our method requires only the accurate measurement of orbital eye
      position (for instance, with a camera-based system), and the position of three
      points on the head. The calculations are expressed in terms of linear algebra, so
      can easily be interpreted and related to the geometry of the human body. Our
      calibration method has been tested experimentally and validated against
      independent data, proving that is it robust even under large translations,
      rotations, and torsions of the head.

PMID- 16890994
TI  - Seasonal variations in bipolar disorder admissions and the association with
      climate: a population-based study.
AB  - OBJECTIVE: Although seasonal influences on bipolar disorder admissions have long
      been observed, the issues of seasonality on different subtypes of mood episodes
      and the effects of associated climatic parameters remain controversial. This
      study sets out to examine seasonal variations in bipolar disorder admissions and
      the association with climate in Taiwan, a subtropical area with fairly constant
      weather conditions. METHODS: This retrospective population-based study uses the
      Taiwan National Health Insurance Research Database for 1999-2003, identifying
      15,060 admissions for bipolar disorder, comprising of 8631 manic, 2078 depressive
      and 4351 mixed/unspecified episodes. The auto-regressive integrated moving
      average model was applied to examine the presence of seasonality and the
      association with climate in each subtype of mood episodes. RESULTS: Admission
      peaks were noted during spring/summer, early winter and early spring, for manic,
      depressive and mixed/unspecified episodes, respectively, while the associations
      with climatic parameters varied between the subtypes of mood episodes.
      CONCLUSIONS: Seasonality in bipolar disorder does exist for all subtypes of mood
      episodes. The distinct seasonal patterns and various associations with the
      climatic parameters imply different underlying mechanisms for the onset of each
      subtype of mood episodes. The association between admission rates and certain
      climatic variables found in this study is informative and could pave the way for
      future studies aimed at exploring the influence of climate on the psychopathology
      of bipolar patients as well as the underlying mechanisms.

PMID- 16890995
TI  - Behavioral activation, inhibition and mood symptoms in early-onset bipolar
      disorder.
AB  - BACKGROUND: Hypomania/mania and depression are hypothesized to correspond to high
      and low expressions of behavioral activation system (BAS) activity, respectively,
      in bipolar individuals. In contrast, behavioral inhibition system (BIS) activity
      is hypothesized to regulate anxiety. The aim of the present study was to examine
      whether self-reported levels of BAS functioning in bipolar adolescents
      corresponded with levels of concurrent manic and depressive symptomatology. The
      secondary aim was to investigate whether self-reported BIS levels were associated
      with self-reported anxiety symptoms. METHODS: Twenty-five adolescents diagnosed
      with bipolar I, II or not otherwise specified were recruited from a treatment
      development study. Adolescents were interviewed using the Depression and Mania
      Rating Scales of the Kiddie Schedule for Affective Disorders and Schizophrenia
      and given the Self-Report for Childhood Anxiety Related Disorders. Next, they
      completed the Behavioral Inhibition/Activation Scales. RESULTS: Contrary to
      hypotheses, adolescents with higher BAS levels exhibited less severe concurrent
      mania symptoms. Furthermore, levels of BAS sensitivity were not associated with
      concurrent levels of depression. As predicted, BIS scores correlated positively
      with self-reported anxiety scores. Adolescents reporting higher levels of the
      motor activity symptoms of mania also reported higher levels of anxiety symptoms.
      LIMITATIONS: The conclusions are based upon cross-sectional analyses in a small
      sample. CONCLUSIONS: In bipolar adolescents, mania and depression appear to be
      independent of self-reported behavioral activation levels. However, mood symptoms
      in adolescent patients are closely tied to components of anxiety, which may lead
      to diminished approach behaviors.

PMID- 16890996
TI  - FR 167653, a p38 mitogen-activated protein kinase inhibitor, suppresses the
      development of endometriosis in a murine model.
AB  - In various cells including endometriotic cells, p38 mitogen-activated protein
      kinase (MAPK) plays essential roles for inflammation, an etiological factor for
      endometriosis. We evaluated the effect of FR 167653, a p38 MAPK inhibitor, on the
      development of endometriosis using a murine model. As an endometriosis model,
      estradiol-treated ovariectomized BALB/c mice were injected intraperitoneally with
      endometrial fragments of the syngenic donor mice. The animals were injected with
      either 30mg/kg FR 167653 or only vehicle (control) s.c. twice a day, starting 2
      days before endometrial injection. Three weeks later, the peritoneal fluids and
      the developed endometriotic lesions were collected. Both the weight of all the
      endometriotic lesions per mouse and the concentrations of interleukin-6 and
      monocyte chemoattractant protein-1 in the peritoneal fluid were significantly
      lower in the FR 167653-treated mice than in the control mice. These findings
      suggest that FR 167653 may inhibit the development of endometriosis possibly by
      suppressing peritoneal inflammatory status.

PMID- 16890997
TI  - Should additional symptoms be included in criteria for atypical depression?
AB  - Analyses of a systematic household sample of 750 respondents aged 11-22, 19 with
      atypical depression, find atypical depression associated with fear of fat,
      insomnia, headache, and fatigue. Other research suggests adding these symptoms to
      criteria for atypical depression, rendering them quite similar to criteria used
      in studies of somatic depression.

PMID- 16890998
TI  - Assessment of the quantitative real-time polymerase chain reaction using a cDNA
      standard for human group A rotavirus.
AB  - Nucleic acid amplification techniques are used frequently for rapid diagnosis of
      viral diseases. In this study, a real-time polymerase chain reaction protocol
      that uses primers specific for the viral VP4 gene and the commercial SYBR Green
      reagent were evaluated for the quantitative measurement of human rotavirus (HRV)
      RNA in human stool specimens. SYBR Green I detection involved analysis of the
      melting temperature of the PCR product and measurement of fluorescence at the
      optimum temperature. The assay resulted in a sensitive and reproducible detection
      of targets ranging from low (<10(2)rotavirus cDNA copies/reaction) to high
      numbers (>10(6)rotavirus cDNA copies/reaction). No cross-reaction was found with
      crude cell culture stocks of coxsackievirus, echovirus, poliovirus, hepatitis A
      virus and adenovirus. Analysis with the HRV cDNA standard demonstrated high
      reproducibility with a coefficient of variation (CV) of 0.2-0.9%. Daily
      performance among three different laboratories showed a CV no greater than 8%,
      indicating an intermediate level of variation. These results demonstrate the
      feasibility of this method for quantitative analysis of human rotavirus in
      clinical samples.

PMID- 16890999
TI  - Ampakines and the threefold path to cognitive enhancement.
AB  - Ampakines are the first peripherally administered drugs that increase excitatory
      monosynaptic responses in the brain. Because of this effect, the compounds
      improve communication in complex networks, potently facilitate long-term
      potentiation (LTP) and induce the expression of neurotrophic factors. Ampakines
      are effective in animal models of neuropsychiatric disorders and have produced
      positive results in a small number of human studies. Neurobiological
      considerations and modeling studies suggest that the drugs, in addition to their
      effects on disturbed behavior, will alter the encoding and organization of
      information in normal brains. Results from physiological and behavioral studies
      accord with this prediction. Building on these findings, this article considers
      how the threefold effects of ampakines will modify, and enhance, cognition.

PMID- 16891000
TI  - Acid-sensing ion channels: advances, questions and therapeutic opportunities.
AB  - Extracellular acid can have important effects on neuron function. In central and
      peripheral neurons, acid-sensing ion channels (ASICs) have emerged as key
      receptors for extracellular protons, and recent studies suggest diverse roles for
      these channels in the pathophysiology of pain, ischemic stroke and psychiatric
      disease. ASICs have also been implicated in mechanosensation in the peripheral
      nervous system and in neurotransmission in the central nervous system. Here, we
      briefly review advances in our understanding of ASICs, their potential
      contributions to disease, and the possibility for their therapeutic modification.

PMID- 16891001
TI  - StpC-based gene therapy targeting latent reservoirs of HIV-1.
AB  - The ability of HIV-1 to form latent reservoirs presents a major obstacle to
      eradication. One approach to elimination of the latent reservoir is induction
      therapy, whereby cells harboring latent virus are activated and therefore
      initiate virus replication. We have constructed a lentiviral vector encoding
      Herpesvirus saimiri subgroup C saimiri transformation-associated protein (StpC),
      which has been shown to modulate HIV-1 replication, under the control of a
      cytomegalovirus promoter in order to determine the ability of StpC to upregulate
      latent HIV-1. We have included a suicide gene, herpes simplex virus thymidine
      kinase (TK), under the control of the HIV-1 long terminal repeat (LTR) promoter.
      We hypothesized that upon StpC expression in latently infected cells induction of
      virus replication and subsequent production of viral transactivators of the LTR
      will activate expression of the tk gene, sensitizing the cells to the nucleoside
      analogue ganciclovir (GCV). Transduction of the latently infected cell line J1.1
      resulted in increased virus replication. In the presence of GCV transduced cells
      exhibited decreased HIV-1 replication, inhibition of cell proliferation, and
      increased apoptosis. This prototype vector serves as a proof of concept of the
      utility of gene-based induction agents and suicide genes as a new method for
      targeting reservoirs of latent HIV-1.

PMID- 16891003
TI  - Hereditary hemochromatosis.
AB  - The advent of the genetics era has profoundly changed the way we look at iron
      related diseases, particularly hemochromatosis. New discoveries have challenged
      historical concepts about the disease, such as its monogenic nature, intestinal
      origin or complete phenotypic penetrance. This review presents a new concept of
      hemochromatosis which stems from the idea that, beyond their genetic diversities,
      all known hemochromatoses have in common the same metabolic abnormality: the
      genetically determined failure to prevent unneeded iron from entering the
      circulatory pool. Inappropriate levels of hepcidin, the iron hormone, appear now
      as the central pathogenic event in all forms of hemochromatosis: depending on the
      protein involved, and its effect on hepatic production of hepcidin, the phenotype
      varies, ranging from massive early-onset iron loading with severe organ disease
      (e.g., associated with homozygous mutations of hemojuvelin or hepcidin itself) to
      the milder late-onset phenotype characterizing the classic and highly prevalent
      HFE-related form or the rare transferrin receptor 2-related form. In vitro and in
      vivo studies will be needed to dissect the consequences of each hereditary
      hemochromatosis allele and increase our understanding of the precise contribution
      of each gene to the hereditary hemochromatosis phenotype.

PMID- 16891002
TI  - Larval exposure to environmentally relevant mixtures of alkylphenolethoxylates
      reduces reproductive competence in male fathead minnows.
AB  - The ubiquitous presence of nonylphenolethoxylate/octylphenolethoxylate (NPE/OPE)
      compounds in aquatic environments adjacent to wastewater treatment plants (WWTP)
      warrants an assessment of the endocrine disrupting potential of these complex
      mixtures on aquatic vertebrates. In this study, fathead minnow larvae were
      exposed for 64 days to a mixture of NPE/OPE, which closely models the NPE/OPE
      composition of a major metropolitan WWTP effluent. Target exposure concentrations
      included a total NPE/OPE mixture load of 200% of the WWTP effluent concentration
      (148microg/L), 100% of the WWTP effluent concentration (74microg/L) and 50% of
      the WWTP effluent concentration (38microg/L). The NPE/OPE mixture contained 0.2%
      4-t-octylphenol, 2.8% 4-nonylphenol, 5.1% 4-nonylphenolmonoethoxylate, 9.3% 4
      nonylphenoldiethoxylate, 0.9% 4-t-octylphenolmonoethoxylate, 3.1% 4-t
      octylphenoldiethoxylate, 33.8% 4-nonylphenolmonoethoxycarboxylate, and 44.8% 4
      nonylphenoldiethoxycarboxylate. An additional exposure of 5microg/L 4-nonylphenol
      (nominal) was conducted. The exposure utilized a flow-through system supplied by
      ground water and designed to deliver consistent concentrations of applied
      chemicals. Following exposure, larvae were raised to maturity. Upon sexual
      maturation, exposed male fish were allowed to compete with control males in a
      competitive spawning assay. Nest holding ability of control and exposed fish was
      carefully monitored for 7 days. All male fish were then sacrificed and analyzed
      for plasma vitellogenin, developmental changes in gonadal tissues, alterations in
      the development of secondary sexual characters, morphometric changes, and changes
      to reproductive behavior. When exposed to the 200% NPE/OPE treatment most larvae
      died within the first 4 weeks of exposure. Both the 100% and 50% NPE/OPE
      exposures caused a significant decrease in reproductive behavior, as indicated by
      an inability of many of the previously exposed males to acquire and hold a nest
      site required for reproduction. In contrast, the 5microg/L 4-nonylphenol exposure
      resulted in significantly enhanced reproductive behavior compared to that of
      control males and a majority of the nesting sites were held by previously exposed
      males. No significant change in the development of gonadal tissues was observed.
      The 100% NPE/OPE exposure resulted in a significant reduction in the gonadal
      somatic index and in the prominence of secondary sexual characteristics of
      exposed larvae. This study indicates that NPE/OPE mixtures have an effect on the
      reproductive competence of previously exposed male fathead minnows. In addition,
      4-nonylphenol concentrations utilized in all exposures were below regulatory
      guidelines, suggesting that evaluation of 4-nonylphenol alone may not be
      sufficient for identifying potentially adverse effects of this suite of compounds
      usually found as mixtures in the aquatic environment.

PMID- 16891004
TI  - Stress-induced heart symptoms and perceptual biases in patients with congenital
      heart disease.
AB  - BACKGROUND: The aim of the present study is to clarify whether biased symptom
      perception towards heart symptoms may explain a reduced quality of life in
      patients with congenital heart disease (ConHD). The present study tested the
      hypothesis that the combination of ConHD and high trait anxiety increases the
      perception of heart symptoms during acute stress. METHODS: 25 patients and 24
      healthy participants completed a stressful computer task. Participant's heart and
      non-heart symptoms were measured after stress and after relaxation. Heart rate,
      blood pressure, respiratory rate, and arterial partial pressure of CO2 were
      monitored continuously. RESULTS: In line with the prediction, a combination of
      high trait anxiety and ConHD resulted in an increased perception of specifically
      heart symptoms during stress. Moreover, the increased perception of heart
      symptoms could not be explained by acute heart dysfunction. CONCLUSIONS: Heart
      dysfunction is not the only cause of an increased perception of heart symptoms. A
      history of disease experience in combination with high trait anxiety may increase
      the perception of heart symptoms during stress and may eventually result in an
      increased risk of developing a reduced quality of life.

PMID- 16891005
TI  - Excimer laser thrombus elimination for prevention of distal embolization and no
      reflow in patients with acute ST elevation myocardial infarction: results from
      the randomized LaserAMI study.
AB  - BACKGROUND: Results for standard revascularization therapies in acute myocardial
      infarction (AMI) have been limited in part by distal embolization, a process
      which might be reduced by the application of ultraviolet laser light. The aim was
      to assess feasibility and safety of excimer laser coronary angioplasty (ELCA) in
      a randomized study in AMI. METHODS: Twenty-seven consecutive patients with ST
      segment elevation AMI (aged 57.8+/-9.2 years) were randomized either to balloon
      angioplasty and stent implantation alone (n=13) or adjunct ELCA (n=14).
      Quantitative coronary angiography was analyzed by an independent core laboratory.
      RESULTS: ELCA was feasible and safe in all cases. No procedure-associated
      complications were observed. Similar results were found for main parameters in
      laser (L) and control (C) patients: diameter stenosis decreased from 94.3+/-9.6
      to 20.7+/-10.3% (L) and from 82.7+/-16.8 to 18.9+/-5.5% (C) (p=ns; L vs. C). TIMI
      flow increased from 0.7+/-1.2 to 2.8+/-0.4 and from 1.7+/-1.5 to 3.0+/-0 (p=ns; L
      vs. C), respectively. The post-procedural myocardial blush score did not differ
      between the groups (2.1+/-1.3 and 2.7+/-1.0; p=ns; L vs. C) and the final
      corrected TIMI frame count (cTFC) was also similar in both groups (23+/-7 and
      22+/-4; p=ns; L vs. C), but the cTFC gain was higher in the laser group (53+/-14%
      and 35+/-20%; p<0.05; L vs. C). CONCLUSIONS: Laser angioplasty is feasible and
      safe for the treatment of patients with ST elevation AMI. Procedural results were
      at least on par with conventional treatment. Further randomized controlled trials
      are needed to assess the benefit of laser angioplasty in AMI.

PMID- 16891006
TI  - Effect of inhaled salbutamol on coronary circulation in humans.
AB  - In 12 patients we assessed the effect of inhaled salbutamol on the coronary
      circulation. According to our results, large doses of salbutamol increase
      coronary flow, but not in proportion to the needs of the myocardium (as
      documented by the increase in coronary oxygen extraction), and decrease coronary
      flow reserve. These effects may have deleterious consequences in patients with
      coronary artery disease, causing or worsening myocardial ischemia.

PMID- 16891007
TI  - Obesity is associated with higher mortality in patients with cardiogenic shock.
AB  - Cardiogenic shock is the leading cause of death in patients with acute myocardial
      infarction. Studies that have focused on identifying mortality predictors in
      patients with cardiogenic shock have not evaluated outcomes in obese patients. A
      study of sixty-one patients with cardiogenic shock demonstrated that obese
      patients with cardiogenic shock have a higher mortality risk compared to non
      obese patients.

PMID- 16891008
TI  - Self-management of oral anticoagulant therapy: a systematic review and meta
      analysis.
AB  - BACKGROUND: A number of randomized controlled trials have compared self
      management of oral anticoagulant therapy with conventional management. However,
      the results have not appeared consistent and a systematic review and meta
      analysis are therefore needed in order to evaluate self-management of oral
      anticoagulant therapy. The aim of this study was to evaluate the efficacy and
      safety of self-management of oral anticoagulant therapy for patients on long-term
      oral anticoagulant therapy. METHODS: A systematic review and meta-analysis
      including randomized controlled trials with highly selected patients comparing
      self-management of oral anticoagulant therapy with conventional treatment. Data
      were extracted in terms of study characteristics, quality of trials and outcome
      (death, minor and major complications (thromboembolic and bleeding events), and
      time within therapeutic INR target range). RESULTS: Ten trials with a total of
      2724 patients were included. Two of the trials could be classified as high
      quality trials. Considering all trials, self-management was associated with a
      reduced risk of death (relative risk (RR)=0.48, 95% confidence interval (CI) 0.29
      0.79, p=0.004), major complications (RR=0.58, 95% CI 0.42-0.81, p=0.001) and with
      increasing time within therapeutic INR target range (weighted mean
      difference=6.53, 95% CI 2.24-10.82, p=0.003). No clear effect was found regarding
      minor complications (RR=0.98, 95% CI 0.49-1.99, p=0.96). CONCLUSIONS: A majority
      of the existing trials have various methodological problems. However, self
      management of oral anticoagulant therapy appeared at least as good and possible
      better than conventional management in highly selected patients.

PMID- 16891009
TI  - Effect of peroxisome proliferator-activated receptor gamma ligand. Rosiglitazone
      on left ventricular remodeling in rats with myocardial infarction.
AB  - BACKGROUND: Recent studies have demonstrated that PPARgamma ligands have anti
      inflammatory effect which is involved in ventricular remodeling. So we
      hypothesized that PPARgamma ligand may have beneficial effects on post-infarct
      ventricular remodeling. METHODS: Experimental myocardial infarction (MI) was
      induced in SD rats by ligation of the left coronary artery. Twenty-four hours
      after surgery, survival rats were randomly divided into MI group and
      Rosiglitazone (MI+Ros) group which would take rosiglitazone 3 mg/kg day for 8
      weeks. After 8 weeks treatment, left ventricular hemodynamics were measured and
      organs were weighed. Myocardial collagen analysis was determined in Van Gieson
      staining by quantitative morphometry. Myocardial angiotensin II and aldosterone
      were detected by radioimmunoassay. Myocardial AT1 and AT2 mRNA expression were
      determined by RT-PCR. RESULTS: Only 1 rat in MI group died of anesthesia at the
      8th week. Rosiglitazone treatment could improve left ventricular +/-dp/dt(max),
      collagen volume fraction and perivascular circumferential area; reduce lung/body
      mass ratio and liver/body mass ratio; inhibit myocardial angiotensin II and
      aldosterone; and had no significant effects on myocardial AT1 and AT2 mRNA.
      Plasma insulin and blood glucose were comparable between two groups. CONCLUSIONS:
      PPARgamma ligand has neutral effect on mortality and beneficial effect on post
      infarct ventricular remodeling, partly by suppressing myocardial angiotensin II
      and aldosterone, irrespective of plasma insulin and blood glucose level.

PMID- 16891010
TI  - Clinical presentation is the main predictor of in-hospital death for patients
      with acute type A aortic dissection admitted for surgical treatment: a 25 years
      experience.
AB  - BACKGROUND: This retrospective analysis assessed the hypothesis that clinical
      status on admission more than other variables related to surgical or post
      operative management may influence in-hospital mortality after surgical treatment
      of acute type A aortic dissection. METHODS: Between January 1979 and April 2004,
      311 patients, mean age of 59.5+/-13 years (range, 18 to 88 years), with acute
      type A aortic dissection were referred for surgery. Logistic regression analysis
      was applied to demographics, etiological, clinical, and surgical variables, to
      identify independent predictors of in hospital death. RESULTS: In hospital
      mortality rate was 23%. Univariate analysis showed older age (p=0.03,
      OR1.02/yrs), cardiac tamponade (p=0.001; OR 2.43), hypotension (p=0.0001; OR 8),
      myocardial ischemia (p=0.005; OR 7), acute renal failure (p=0.0001; OR 4.16),
      limb ischemia (p=0.0002; OR 3.3), neurological deficits pre-op (p=0.0001; OR
      8.5), and mesenteric ischemia (p=0.003) as independent predictors of in-hospital
      death. Multivariate analysis identified the following presenting variables as
      predictors of in-hospital death: hypotension (p=0.003; OR 7.4), myocardial
      ischemia (p=0.03; OR 5.8), mesenteric ischemia (p=0.009), acute renal failure
      (p=0.0001; OR 3.9), neurological deficits (p=0.0001; OR 7.7). In-hospital
      mortality for the group of patients presenting with at least one of the tested
      pre-operative complications (N=158; 51%) was 33% vs 12% (p=00001). No other
      variables emerged as significant for in-hospital death. CONCLUSION: In an era of
      standardized surgical technique, expeditious referral and intervention by
      lowering preoperative dissection-related complications and co-morbidities might
      represent the most efficacious tool to improve results.

PMID- 16891011
TI  - Immediate and chronic effects of AV-delay optimization in patients with cardiac
      resynchronization therapy.
AB  - BACKGROUND: Acute changes of the AV-delay in CRT patients have a significant
      impact on hemodynamics. However, the chronic functional effects of AV-delay
      optimization have not been systematically examined despite of their potential
      role for chronic functional improvement. METHODS: Therefore, in this study we
      investigated whether optimization of AV-delay in CRT patients as assessed by
      echocardiographic measurement of the velocity time integral of the left
      ventricular outflow tract (LVOT-VTI) chronically changes (1) echocardiographic
      parameters of systolic and diastolic left ventricular function, (2) walking
      distance in the 6-min walk test, (3) levels of NT-proBNP and (4) quality of life
      as assessed by a standard questionnaire. 33 patients underwent optimization of AV
      delay 31+/-8 weeks after initiation of CRT. Follow up (FU) was conducted 43+/-5
      days later. RESULTS: E/Ea, the ratio of peak E-wave of mitral inflow and of TDI
      of the mitral annulus, significantly decreased immediately post-optimization
      (11+/-1 vs. 14+/-1 at baseline, p<0.05) and further decreased at FU (8+/-1,
      p<0.05 vs. immediately post-optimization) indicating improvement of diastolic
      function, while traditional parameters of diastolic function derived from pulse
      wave Doppler remained unchanged. There was a slight increase of LV-ejection
      fraction as assessed by echocardiography acutely after optimization (baseline:
      25+/-2%, optimized: 28+/-1%, p<0.05), while LV-ejection fraction at FU did not
      differ from baseline. 6-min walk test improved from 449+/-17 m (baseline) to
      475+/-17 m at FU (p<0.05). During this period NT-proBNP significantly decreased
      from 3193+/-765 ng/l to 2593+/-675 ng/l (p<0.05). Quality of life was unchanged
      at FU. CONCLUSION: This study demonstrates for the first time chronic functional
      improvement due to AV-delay optimization in patients with CRT.

PMID- 16891012
TI  - The evaluation of gastro-oesophageal reflux and oesophagocardiac reflex in
      patients with angina-like chest pain following cardiologic investigations.
AB  - The aims of the study were to assess pathogenetic role of gastro-oesophageal
      reflux and the oesophago-cardiac reflex in subjects with chest pain. To evaluate
      the prevalence of gastro-oesophageal reflux disease and the oesophago-cardiac
      reflex in patients with different coronary artery diseases and in coronary spasm.
      PATIENTS, METHODS: Fifty-one patients with chest pain were enrolled after
      detailed cardiologic evaluation including coronary angiography. The prevalence of
      gastrooesophageal reflux disease was established by symptom analysis, upper
      gastrointestinal endoscopy, 24-h oesophageal pH monitoring, and oesophageal
      manometry. The oesophago-cardiac reflex was established by oesophageal acid
      perfusion test (0.1 N HCl and 0.9% NaCl, 120-120 ml/10 min in a blinded manner)
      combined with transoesophageal Doppler echocardiographic coronary flow
      measurement in the left anterior descending artery. RESULTS: Gastro-oesophageal
      reflux disease was established in 45% (23/51) of the patients. Oesophageal acid
      perfusion decreased the coronary flow velocity in 49% (25/51) of the patients
      indicating the presence of oesophago-cardiac reflex. Oesophago-cardiac reflex was
      present more frequently in patients with coronary spasm, than in patients with
      either epicardial coronary artery disease or microvascular coronary disease
      (p<0.02). Patients with oesophago-cardiac reflex had higher DeMeester scores,
      increased number of reflux episodes, fraction time below pH 4, and prolonged acid
      reflux episodes (p<0.05 for each parameter). CONCLUSIONS: Gastro-oesophageal
      reflux disease is frequently established in patients with either epicardial or
      microvascular coronary artery disease or with coronary spasm. The oesophago
      cardiac reflex was more frequently observed in patients with coronary spasm. The
      combination of oesophageal acid perfusion test and transoesophageal Doppler
      echocardiographic coronary flow measurement seems to be a useful method for the
      detection of this reflex. Patients with prolonged gastro-oesophageal acid reflux
      episodes, erosive oesophagitis and coronary spasm may be at higher risk for the
      development of linked-angina.

PMID- 16891013
TI  - QT dispersion: electrophysiological holy grail or the greatest fallacy in the
      surface ECG?

PMID- 16891014
TI  - Effects of GM-CSF on the stem cells mobilization and plasma C-reactive protein
      levels in patients with acute myocardial infarction.
AB  - BACKGROUND: Stem cell mobilization with granulocyte colony-stimulating factor (G
      CSF) has been proposed to improve cardiac function and prevent ventricular
      remodeling after acute myocardial infarction (AMI) in preclinical and clinical
      studies. It has been demonstrated that granulocyte-macrophage colony-stimulating
      factor (GM-CSF) can improve collateral flow in patients with coronary artery
      disease. In this study, we used GM-CSF to mobilize the bone marrow stem cells
      (BMSCs) in patients with AMI and assessed the safety, feasibility and efficacy of
      this treatment. METHODS: Twenty patients with AMI were randomly divided into GM
      CSF group (10 microg/kg body weight, for 7 days) and control group (saline). The
      absolute counts of CD34 positive cells in peripheral blood were enumerated with
      flow cytometry. Plasma levels of C-reactive protein (CRP), interleukin-6 (IL-6)
      and tumor necrotic factor-alpha (TNF-alpha) were measured on days 1, 3, 7, 10 and
      14. Echocardiography (UCG) was done on day 7 and after 12 months. RESULTS:
      Peripheral CD34 positive cells in GM-CSF patients obviously increased shortly
      after using GM-CSF and peaked on day 7 (p<0.01 versus controls). GM-CSF group had
      significantly higher mean level of plasma CRP than controls on day 10 (p<0.05).
      The levels of IL-6 and TNF-alpha in therapy patients were as same as in controls.
      Left ventricular ejection fraction (EF) at 12 months was significantly greater
      than that on day 7 in GM-CSF patients (p<0.05). The EF in controls had no obvious
      differences in follow-up. There were no statistically differences regarding the
      left ventricular end-systolic volume (LVESV), the left ventricular end-diastolic
      volume (LVEDV) and the resting wall thickening (WT) in the infarct zone in two
      groups in follow-up. CONCLUSIONS: Our results demonstrate that GM-CSF can
      effectively mobilize the CD34 positive cells and at the same time may increase
      the levels of plasma CRP in patients with AMI. The remote effects of this drug
      need to be further defined.

PMID- 16891015
TI  - Virtual intraluminal evaluation of aortico-left ventricular tunnel by multislice
      computed tomography.
AB  - The aortico-left ventricular tunnel (ALVT) is a rare abnormal channel that arises
      from the right coronary sinus through the right ventricular outflow tract to
      enter the left ventricle below the aortic valve. The unique ability of multislice
      computed tomography (CT), as applied in the virtual coloscopy, has not been well
      established in patients with cardiovascular diseases. We herein investigate the
      virtual intraluminal image in a patient with an ALVT. An 18-year-old male was
      admitted with a 6-month-long history of progressive exertional dyspnea. He was
      diagnosed to suffer from ALVT at 5 months of age and received prosthetic patch
      closure of the aortic opening of the tunnel with mild residual aortic
      regurgitation. On admission this time, physical examination revealed a grade 3/6
      diastolic murmur over the right upper sternal border. A 16-row multislice CT
      angiography demonstrated an ALVT. In the 3D reconstructed images, the orifice and
      intraluminal structure of ALVT were clearly visualized at different levels,
      similar to a real intracardiac endoscopic images. The patient was then referred
      for aortic valve replacement due to heart failure caused by severe degenerative
      aortic insufficiency. Our case displayed successfully not only the entire
      location of ALVT but also demonstrated the virtual intraluminal imaging mimicking
      endoscopy. This technique provides the virtual visualization of the entire inner
      image of AVLT, which may not be possible with other imaging modalities.

PMID- 16891016
TI  - A giant aortocaval fistula due to abdominal aortic aneurysm.
AB  - Although very rare, the fistula development between vena cava inferior and an
      abdominal aortic aneurysm is a pathology which can deteriorate the clinical
      status of the patient rapidly. Today, this pathology can be diagnosed very easily
      with non-invasive tests, and invasive tests can also be used for diagnostic
      purposes when needed. Especially spiral computed tomography scan with contrast is
      usually sufficient to diagnose this pathology. A large-diameter aortocaval
      fistula case, which to our knowledge never presented in the literature before,
      and its diagnosis and treatment will be presented in this article.

PMID- 16891017
TI  - Coronary artery dissection after blunt chest trauma: depiction at multidetector
      row computed tomography.
AB  - Coronary artery dissection after blunt chest trauma has rarely been reported in
      traumatic cardiac injuries, but it may cause fatal or nonfatal myocardial
      infarction. We report a case of dissection of the left main coronary artery,
      which resulted in acute myocardial infarction 5 weeks after blunt chest trauma.
      Multidetector-row computed tomography performed prior to the onset of infarction
      depicted intimal flap and dissected cavities.

PMID- 16891018
TI  - Dendritic cells and autoimmune heart failure.
AB  - Dilated cardiomyopathy is the most common cause of heart failure in young
      patients and often results from autoimmunity triggered by viral or bacterial
      infections. Dendritic cells are professional antigen-presenting cells residing in
      lymphatic tissue and in the heart. They are involved in both, host defense and
      maintenance of peripheral tolerance. Animal models suggest an important role for
      dendritic cells in the induction of autoimmune myocarditis. Activated and self
      antigen loaded dendritic cells, for example, induce myocarditis and heart failure
      in susceptible mice. It appears that the combined presence of tissue damage and
      innate activation exceeding a certain threshold prompts dendritic cells to prime
      and amplify potentially autoreactive T cells targeting the heart. The concept of
      dendritic cell induced myocarditis helps us to understand disease pathogenesis
      and offers a nice approach to develop novel therapeutic strategies against a
      devastating heart disease.

PMID- 16891019
TI  - The research of molecular and ionic mechanisms in vagally mediated atrial
      fibrillation in canine.
AB  - BACKGROUND: The reentrant mechanism of vagally mediated AF is not clearly
      elucidated. METHODS AND RESULTS: After vagal stimulation, thirty dogs were
      divided AF group (AF could be induced) and control group (AF could not be
      induced). Western blot and patch clamp were used to determine M(2) receptor and
      I(K,ACh) in left atrial appendage (LAA), right atrial appendage (RAA), left
      atrium (LA), right atrium (RA), pulmonary veins (PVs) and superior vena cava
      (SVC). In control group, the densities of M(2) receptor and I(K,ACh) in LAA, RAA
      and LA were higher than that in RA, PVs and SVC. However, there was no
      significant difference in LAA, RAA and LA. In AF group, the densities of M(2)
      receptor and I(K,ACh) in LAA, RAA and LA were higher than that in RA, PVs and
      SVC. Furthermore, the densities of the M(2) and I(K,ACh) in LAA and RAA were
      higher than that in LA. CONCLUSIONS: Atrial appendage perhaps play an important
      role in initiation of cholinergic AF. However, PVs and SVC less often play an
      important role in vagotonic paroxysmal AF.

PMID- 16891020
TI  - Antiproliferative effects of EGFR tyrosine kinase inhibition and radiation
      induced genotoxic injury are attenuated by adhesion to fibronectin.
AB  - BACKGROUND AND PURPOSE: Integrin-linked kinase (ILK) functions in cooperative
      integrin-growth factor receptor-mediated signaling to control cell survival and
      proliferation. The effect of tyrosine kinase (tk) inhibition of the epidermal
      growth factor receptor (EGFR) on radiation survival and growth was evaluated in
      human FaDu squamous cell carcinoma cells expressing different forms of ILK.
      MATERIAL AND METHODS: ILK-wild-type (wk) and -hyperactive kinase (hk) transfected
      cells were grown on fibronectin (Fn) under serum presence or depletion,
      irradiated (0-6Gy) and/or treated with the EGFR-tk inhibitor BIBX1382BS. RESULTS:
      ILK-wk and -hk transfectants showed significant radiosensitization compared to
      vector control cells. Antisurvival and antiproliferative effects of EGFR-tk
      inhibition plus/minus irradiation were counteracted by adhesion to Fn relative to
      the control substratum, poly-L-lysine. Similar to vector controls, ILK
      transfectants exhibited a strong decrease in cell proliferation but no enhanced
      radiation sensitivity after EGFR-tk inhibition. This decrease was accompanied by
      changes in cyclin D1 and phosphorylated MAPK persisting to day 10 following
      transient drug exposure. CONCLUSIONS: Our data demonstrate a prosurvival role of
      adhesion and an antisurvival role of ILK upon irradiation. Inhibition of EGFR-tk
      using BIBX1382BS does not affect the intrinsic cellular radiosensitivity of cells
      grown on fibronectin. Thus, simultaneous targeting of adhesion and growth factor
      receptor-mediated signaling might potently improve anticancer strategies.

PMID- 16891021
TI  - Eye-hand interactions in tracing and drawing tasks.
AB  - We report a preliminary analysis of the interactions between eye and hand during
      tracing and drawing of four simple shapes. Eye and hand movements were recorded
      using the ASL 504 system and the Flock of Birds system, respectively. During
      tracing, pen tip and eye were tightly coupled, with participants making a series
      of small saccades just in front of the moving pen, interspersed with periods of
      smooth pursuit. During drawing, saccades were fewer and larger and pursuit was
      less frequent. Observed eye-hand interactions suggested a bidirectional
      relationship between the eye and hand. These findings are explained in terms of
      the differing degree that the two tasks employ visual detail, external or
      internal cues and eye-hand coordination.

PMID- 16891022
TI  - Testing of pathogenic Yersinia enterocolitica in pig herds based on the natural
      dynamic of infection.
AB  - This study was performed to evaluate testing methods of pathogenic Yersinia
      enterocolitica in pigs at different ages. Relevant tools and procedures are
      crucial if pig herds should be declared free from pathogenic Y. enterocolitica.
      Historical data based on serology showed that the two farms investigated in this
      study (herds A and B) were contaminated with Y. enterocolitica O:3 since at least
      1995. Laboratory investigations of 60 pigs were sampled one to four times (herd
      A) and 20 pigs were sampled one to three times (herd B) at different ages were
      the basis for this report. The following testing procedures could be used to
      conclude that a herd is free from pathogenic Y. enterocolitica:--serological
      testing of pigs could be performed as a basis for categorisation for all ages
      from about 100 days including at slaughter when the pigs are 150-180 days old, -
      bacteriological examination of faeces could be used as a basis for categorisation
      at all ages from 85 days until about 135 days, --bacteriological examination of
      tonsils could be used as a basis for categorisation at all ages from 85 days
      including at slaughter when the pigs are 150-180 days old. However, due to animal
      welfare aspects, one should avoid sampling of tonsils. Accordingly, the
      serological method or bacteriological examination of faeces at relevant ages
      should be preferred. One aspect related to slaughter hygiene is that in pigs
      slaughtered at the age of 135 days or more, the tonsils may be a more significant
      source of human pathogenic Y. enterocolitica than faeces.

PMID- 16891023
TI  - Survival of Enterobacter sakazakii on fresh produce as affected by temperature,
      and effectiveness of sanitizers for its elimination.
AB  - A study was done to determine the survival characteristics of Enterobacter
      sakazakii on the surface of apples, cantaloupes, strawberries, lettuce, and
      tomatoes stored at 4, 12, and 25 degrees C for 8-28 days. Populations
      significantly decreased (p<or=0.05) on all test produce at all storage
      temperatures. The efficacy of chlorine, chlorine dioxide, and a peroxyacetic acid
      based sanitizer (Tsunami 200) treatments (1 and 5 min) in killing the bacterium
      on apples, tomatoes, and lettuce was determined. Chlorine and chlorine dioxide,
      at >or=50 microg/ml, were equivalent in killing E. sakazakii on apples.
      Populations of E. sakazakii on apples treated with 10 microg/ml chlorine dioxide
      for 1 or 5 min were significantly reduced (p<or=0.05) by 3.38 and 3.77 log
      CFU/apple, respectively, compared to the number remaining on apples after washing
      with water. Treatment with Tsunami 200 at 40 microg/ml for 1 min caused
      reductions of >or=4.00 log CFU/apple. Reductions of >or=3.70 log CFU/tomato were
      achieved by treatment with 10 microg/ml chlorine or chlorine dioxide or 40
      microg/ml Tsunami 200 for 5 min. Reductions in populations of E. sakazakii on
      lettuce treated with chlorine at 10, 50, and 100 microg/ml for 1 min ranged from
      1.61 to 2.50 log CFU/sample (26+/-4 g), compared to populations remaining on
      lettuce washed with water. Chlorine was less effective in killing E. sakazakii on
      lettuce than on apples or tomatoes. Treatment of lettuce with Tsunami 200 (40 and
      80 microg/ml) for 5 min caused a reduction of >or=5.31 log CFU/sample. Results
      provide insights to predicting survival characteristics of E. sakazakii on
      produce and the efficacy of sanitizers in killing the bacterium.

PMID- 16891025
TI  - Efficient expression of the 15-kDa form of infectious pancreatic necrosis virus
      VP5 by suppression of a UGA codon.
AB  - Infectious pancreatic necrosis virus (IPNV), a member of the Birnaviridae family,
      encodes a nonstructural VP5 protein from a small open reading frame (ORF), which
      overlaps with a major ORF encoding pVP2, VP4 and VP3 proteins. In majority of the
      Sp strains of IPNV sequenced to date, VP5 gene codes for a 15-kDa protein.
      However, we have shown that in highly virulent strains, there is a premature in
      frame stop codon (UGA) at nucleotide (nt) position 427, (preceding the 15-kDa
      stop codon at nt position 511) which could encode a 12-kDa protein. Using reverse
      genetics, we recovered recombinant rNVI15, rNVI15-15K and rNVI15-DeltaVP5 viruses
      (which could encode 12 or 15-kDa VP5 or lack the expression of VP5, respectively)
      and demonstrated that VP5 is dispensable for viral replication in vivo but is not
      involved in virulence (Santi, N., Song, H., Vakharia, V. N., Evensen, O., 2005a.
      Infectious pancreatic necrosis virus VP5 is dispensable for virulence and
      persistence. J. Virol. 79, 9206-9216). Here, we utilized these viruses to
      investigate the gene expression of VP5 in vitro. Our results indicate that a 15
      kDa VP5 is produced in rNVI15-infected cells, albeit at lower levels than in
      rNVI15-15K-infected cells, suggesting that the opal stop codon at nt 427 is
      suppressed. Furthermore, to examine translational suppression of the opal stop
      codon in VP5 gene, we constructed plasmids containing VP5-specific sequence and
      employed a yeast-based bicistronic dual-luciferase reporter system (Harger, J.W.,
      Dinman, J.D., 2003. An in vivo dual-luciferase assay system for studying
      translational recoding in the yeast Saccharomyces cerevisiae. RNA 9, 1019-1024).
      Our results demonstrate that the VP5 sequence (with or without a stop codon)
      yielded approximately 13% termination suppression and the efficiency is directly
      related to the base immediately 3' of the termination codon, C>A>U>G.

PMID- 16891024
TI  - Intracellular redox equilibrium and growth phase affect the performance of
      luciferase-based biosensors.
AB  - Light emission from the bacterial luciferase operon has been variously exploited
      during last two decades. The use of convenient inducible promoters has granted
      significant degrees of specificity to whole cell-based assays for high-throughput
      screening and environmental monitoring. Nevertheless, unexplained unspecific
      responses have been repeatedly reported. Here, we show that the impairment of the
      intracellular biochemical equilibrium interferes with the luminescence produced
      by Escherichia coli and Staphylococcus aureus strains carrying the lux operon
      under constitutive or inducible control. Compounds as trimethoprim and
      methotrexate, by indirectly inducing NADPH accumulation, enhance light emission.
      Conversely, molecules driving the cell toward an oxidized state, as dimethyl
      sulfoxide, inhibit luminescence. These findings fit into the accepted biochemical
      pathway for bioluminescence, where NADPH and reducing equivalents are necessary
      for the production of luciferase substrates, although they do not directly take
      part into the light-emitting reaction. Moreover, we investigated the influence of
      induction timing upon the bioluminescence response from inducible reporter
      systems and demonstrated a correlation between the emitted light and the growth
      phase at which induction is performed. Our results provide explanations for some
      unspecific responses recorded so far in whole cell-based luminescent biosensors
      and emphasize the intrinsic limitations of this kind of reporting system.

PMID- 16891026
TI  - PEI-alginate nanocomposites as efficient in vitro gene transfection agents.
AB  - The positive charge on PEI was partially shielded by forming ionic nanocomposites
      with a polysaccharide, alginic acid, in aqueous solution, bypassing tedious
      chemical synthesis. The content of alginic acid was varied systematically to
      obtain a series of nanocomposites. The nanocomposites were first characterized by
      assessing the surface charge (zeta potential), size (DLS) and morphology (AFM)
      followed by evaluation for their DNA interaction ability, cytotoxicity and
      transfection efficiency on various cell lines. The transfection efficiency of PEI
      alginate (6.26%) nanocomposites improved dramatically (2-16-fold over native PEI)
      in all the cell lines studied. However, a decrease in transfection efficiency was
      observed on deviating from this optimal concentration of alginic acid in
      nanocomposites. Cytotoxicity of PEI-alginate/DNA complexes was nearly abolished
      on increasing the concentration of alginic acid in nanocomposites. PEI-alginate
      (6.26%) nanocomposites also delivered SiRNAs efficiently into mammalian cells,
      resulting in 80% suppression of GFP expression. The cellular uptake and endosomal
      escape of PEI-alginate nanocomposites and PEI were found to follow a similar
      route when transfection was carried out in presence of chloroquine, bafilomycin
      A1, cytochalasin B and methyl-beta-cyclodextrin. The results demonstrate a
      versatile vector that can be used for efficient cytoplasmic delivery of a broad
      range of nucleic acids.

PMID- 16891027
TI  - A polymeric micelle MRI contrast agent with changeable relaxivity.
AB  - Polymeric micelles were formed from cationic polymers (polyallylamine or
      protamine) and anionic block copolymers (poly(ethylene glycol)-b-poly(aspartic
      acid) derivative) that bound Gd ions providing high contrasts in Magnetic
      Resonance Imaging (MRI) by shortening the T(1) longitudinal relaxation time of
      protons of water. The Gd-binding block copolymer alone showed high relaxivity
      (T(1)-shortening ability) values from 10 to 11 mol(-1) s(-1), while the polymeric
      micelles exhibited low relaxivity values from 2.1 to 3.6 mol(-1) s(-1). These
      findings point to the feasibility of a novel MRI contrast agent that selectively
      provides high contrasts at solid tumor sites owing to a dissociation of the
      micelle structures, while selective delivery to the tumor sites is achieved in
      the polymeric micelle form.

PMID- 16891028
TI  - Imidazole groups on a linear, cyclodextrin-containing polycation produce enhanced
      gene delivery via multiple processes.
AB  - The linear, cyclodextrin-containing polycation (CDP) is one of many non-viral
      gene delivery vectors that show improved transfection efficiency when modified to
      have pH-buffering capacity. The buffering activity is presumed to confer enhanced
      ability to escape the endocytic pathway. Here, the differences in delivery
      behavior between CDP and its pH-buffering, imidazole-containing variant (CDPim)
      are investigated in order to elucidate the mechanism(s) by which these related
      materials exhibit differences in gene delivery. In cell-free assays that include
      dye exclusion and heparan sulfate displacement, CDP appears to have weaker
      binding strength with nucleic acids than CDPim. Numerous analyses involving
      transfected cells, however, indicate that CDPim more readily releases nucleic
      acids in the intracellular setting. Together, these data suggest that differences
      in transfection efficiency between CDP and CDPim result from factors beyond
      buffering activity and endosomal escape.

PMID- 16891031
TI  - A community-based study of chronic kidney disease among type 2 diabetics in
      Kinmen, Taiwan.
AB  - Diabetic nephropathy is the major cause of end-stage renal disease. Many studies
      show that chronic kidney disease can be prevented, or its progression to end
      stage renal disease delayed, by effective intervention. The aim of this study was
      to estimate the prevalence of proteinuria and renal impairment in patients with
      type 2 diabetes. A community-based screening for chronic kidney disease in type 2
      diabetic patients was conducted in 1999-2001. Proteinuria was defined in terms of
      urine protein-to-creatinine ratio. The glomerular filtration rate per 1.73m(2)
      body surface area was calculated using an equation from the Modification of Diet
      in Renal Disease Study. The overall response rate was about 78.6%. Prevalence
      rates of proteinuria and renal impairment were 29.4% and 15.1%, respectively.
      Females had higher prevalence of proteinuria and renal impairment than males. And
      prevalence increased with increasing age. Hypertension was associated with both
      proteinuria and renal impairment. Only 43.0% of patients with stages 3-5 chronic
      kidney disease had proteinuria. Proteinuria and renal impairment screening may
      identify different segments of the diabetic population. Both a glomerular
      filtration rate and proteinuria test are recommended as screening tools for early
      detection of chronic kidney disease in type 2 diabetics.

PMID- 16891029
TI  - BCNU-loaded PEG-PLLA ultrafine fibers and their in vitro antitumor activity
      against Glioma C6 cells.
AB  - The purpose of the present study was to develop implantable BCNU-loaded
      poly(ethylene glycol)-poly(L-lactic acid) (PEG-PLLA) diblock copolymer fibers for
      the controlled release of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). BCNU was
      well incorporated and dispersed uniformly in biodegradable PEG-PLLA fibers by
      using electrospinning method. Environmental Scanning Electron Microscope (ESEM)
      images indicated that the BCNU-loaded PEG-PLLA fibers looked uniform and their
      surfaces were reasonably smooth. Their average diameters were below 1500 nm. The
      release rate of BCNU from the fiber mats increased with the increase of BCNU
      loading amount. In vitro cytotoxicity assay showed that the PEG-PLLA fibers
      themselves did not affect the growth of rat Glioma C6 cells. Antitumor activity
      of the BCNU-loaded fibers against the cells was kept over the whole experiment
      process, while that of pristine BCNU disappeared within 48 h. These results
      strongly suggest that the BCNU/PEG-PLLA fibers have an effect of controlled
      release of BCNU and are suitable for postoperative chemotherapy of cancers.

PMID- 16891033
TI  - Transglutaminase activity decrease during acclimation to hyposaline conditions in
      marine seaweed Grateloupia doryphora (Rhodophyta, Halymeniaceae).
AB  - Polyamines (PAs), such as diamine putrescine (PUT), triamine spermidine (SPD) and
      tetraamine spermine (SPM) have been related to environmental stress, including
      salt stress. A marine red macrophyte alga Grateloupia doryphora (Montagne) Howe
      was used to investigate the role of PAs during acclimation to moderate hyposaline
      conditions (incubation 24h in 18 psu seawater as compared to 36 psu of natural
      seawater). The results obtained showed that a moderate hyposaline shock caused an
      increase in the free fraction of PUT, SPD and SPM, mainly due to a decrease in
      TGase activity, together with an apparent increase in the l-arginine dependent
      PAs synthesis (ODC and arginase decreased, and ADC slightly increased). The
      photosynthetic rate increased in thalli when exposed to free SPD at 18 psu, but
      it did not increase at 36 psu.

PMID- 16891034
TI  - The influence of glutamic and aminoacetic acids on the excitability of the
      liverwort Conocephalum conicum.
AB  - Intracellular microelectrode measurements revealed that a resting potential (RP),
      an action potential (AP) and a calcium component of AP (named voltage transient,
      VT) can be influenced by glutamic acid (Glu) and aminoacetic acid (glycine, Gly)
      in the liverwort Conocephalum conicum. In the continuous presence of 5mM Glu or
      5mM Gly, the RP hyperpolarized constantly and the plants became desensitized to
      the excitatory amino acids (Glu or Gly). Under such circumstances, the amplitudes
      of APs evoked by stimuli other than Glu or Gly grew, as did their calcium
      components (VTs). The sudden application of 1-15 mM Glu or Gly to a thallus not
      yet desensitized resulted in an excitation, i.e. a single AP or AP series.
      Aspartate (Asp) could not substitute for Glu in any way. Simultaneous action of
      both amino acids acted synergically to trigger APs. The same phenomenon was
      observed when glycine solution was enriched with N-methyl-D-aspartic acid (NMDA).
      Gly-induced APs were totally hindered by 1mM D-amino-5-phosphonopentanoic acid
      (AP5)--an inhibitor of ionotropic glutamate receptors of the NMDA kind. Glu
      induced APs could be totally suppressed by 1mM AP5 as well as by 1mM 6,7
      dinitroquinoxaline-2,3-dione (DNQX)--an inhibitor of AMPA/KA receptors. DNQX also
      completely blocked the calcium component of Glu-evoked APs. After DNQX treatment,
      the only response to Glu was a membrane potential hyperpolarization (like the Glu
      response in a desensitized plant). It was concluded that the Glu-induced
      depolarization and hyperpolarization are separate phenomena. The stimulatory
      effects of both Glu and Gly on liverwort excitability may be the consequences of
      an activation of a variety of ionotropic Glu receptor subtypes.

PMID- 16891035
TI  - Neonatal astrovirus gastroenteritis during an inborn nursery outbreak.

PMID- 16891036
TI  - Pioneers in infection control: John Snow, Henry Whitehead, the Broad Street pump,
      and the beginnings of geographical epidemiology.
AB  - John Snow was one of the founders of epidemiology. Already convinced of the value
      of pure water, he analysed the distribution of cholera cases in the 1848 epidemic
      in relation to the purity of the water supply in London. His hypothesis that
      cholera was spread by contaminated water was tested by the 'Broad Street'
      epidemic of 1854. Snow quickly traced the water used in the houses affected by
      cholera to the pump in Broad Street, and persuaded the parish council to remove
      the handle. The epidemic subsided. The council did not really believe Snow, so
      the curate, Henry Whitehead, set out to repeat Snow's work, albeit at a more
      leisurely pace as the epidemic had subsided. He located 700 deaths within a 250
      yard radius and showed that use of water from the Broad Street pump was strongly
      correlated with death from cholera. This surprised him as he had drunk water from
      the pump himself during the outbreak. Thus 'geographical epidemiology' began,
      although it was some years before Snow's observations were generally accepted.

PMID- 16891037
TI  - Bacillus spp. among hospitalized patients with haematological malignancies:
      clinical features, epidemics and outcomes.
AB  - Between April 2000 and May 2005, 350 bacteraemic episodes occurred among patients
      treated in our haematology unit. Two hundred and twenty-eight of these episodes
      were caused by Gram-positive pathogens, most commonly coagulase-negative
      staphylococci and Staphylococcus aureus. One hundred and twenty-two episodes were
      due to Gram-negative pathogens, with a predominance of Escherichia coli,
      Acinetobacter baumannii and Pseudomonas aeruginosa. Bacillus bacteraemias
      constituted 12 of these episodes occurring in 12 patients, and accounted for 3.4%
      of all bacteraemic episodes. Of the 12 strains evaluated, seven were Bacillus
      licheniformis, three were Bacillus cereus and two were Bacillus pumilus. Seven
      episodes presented with bloodstream infection, three with pneumonia, one with
      severe abdominal pain and deterioration of liver function, and one with a
      catheter-related bloodstream infection. B. licheniformis was isolated from five
      patients who had been hospitalized at the same time. This outbreak was related to
      non-sterile cotton wool used during skin disinfection. B. cereus and B.
      licheniformis isolates were susceptible to cefepime, carbapenems, aminoglycosides
      and vancomycin, but B. pumilus isolates were resistant to all antibiotics except
      for quinolones and vancomycin. Two deaths were observed. In conclusion, Bacillus
      spp. may cause serious infections, diagnostic and therapeutic dilemmas, and high
      morbidity and mortality in patients with haematological malignancies. Both B.
      cereus and B. licheniformis may be among the 'new' Gram-positive pathogens to
      cause serious infection in patients with neutropenia.

PMID- 16891038
TI  - Failure of endoscope decontamination.

PMID- 16891039
TI  - Antibiotic use in two cohorts of German intensive care units.
AB  - Antibiotic use was evaluated in two cohorts of intensive care units (ICUs) in
      Germany. One cohort included ICUs participating in a surveillance programme
      (N=34) collecting antibiotic use and bacterial resistance data, with quarterly
      feedback. The second ICU cohort was from a cross-sectional study and represented
      a sample from hospitals in South-west Germany (N=58). Two dose definitions were
      used. These were the World Health Organization/Anatomical Therapeutic Chemical
      Classification (ATC) 2001 definition of defined daily dose (DDD), and a
      definition of recommended daily dose (RDD) that better reflected the currently
      prescribed dosages of parenteral drugs for hospitalized patients. Data were
      expressed as DDD or RDD per 100 patient-days. It was determined whether hospital
      size and affiliation, year of study and ICU type had an influence on overall use
      of antibiotics. Overall use differed between the two ICU cohorts irrespective of
      the dose definitions used. High use of antibiotics was primarily associated with
      hospital affiliation (university vs non-university) and hospital size. Mean
      overall use of antibiotics in non-university hospital ICUs ranged between 106 and
      111 DDD/100 (59 and 67 RDD/100) for different hospital size categories, compared
      with 140 DDD/100 (87 RDD/100) in university hospital ICUs. In conclusion, in
      order to compare the use of antibiotics between ICU cohorts and to assess trends
      over time, data adjustment is required for hospital affiliation and size.

PMID- 16891040
TI  - When alcohol hand rub gets in your eyes.

PMID- 16891041
TI  - Alcohol-based hand rub: influence of healthcare workers' knowledge and perception
      on declared use.
AB  - Handrubbing with alcohol-based hand rub (AHR) is a validated alternative to
      handwashing. The aims of this study were to compare knowledge and declared use of
      AHR between different categories of healthcare worker (HCW), and to assess
      factors associated with the use of AHR. A standardized questionnaire was sent to
      all HCWs in a tertiary care university hospital. The following data were
      collected for each HCW: job title (physician, nurse, nursing assistant or other),
      sources of information about AHR; knowledge and perception of AHR and declared
      use of AHR in daily practice instead of unmedicated or antiseptic soap. Of 5238
      questionnaires, 1811 were returned. Physicians had better knowledge about AHR
      than other HCWs. HCWs' knowledge of AHR efficacy and skin tolerance were
      independently associated with the use of AHR instead of unmedicated or antiseptic
      soap. The declared use of AHR differed according to professional category.

PMID- 16891042
TI  - Neurotensin: role in psychiatric and neurological diseases.
AB  - Neurotensin (NT), an endogenous brain-gut peptide, has a close anatomical and
      functional relationship with the mesocorticolimbic and neostriatal dopamine
      system. Dysregulation of NT neurotransmission in this system has been
      hypothesized to be involved in the pathogenesis of schizophrenia. Additionally,
      NT containing circuits have been demonstrated to mediate some of the mechanisms
      of action of antipsychotic drugs, as well as the rewarding and/or sensitizing
      properties of drugs of abuse. NT receptors have been suggested to be novel
      targets for the treatment of psychoses or drug addiction.

PMID- 16891043
TI  - Synthesis and antitumour activity of new muricatacin and goniofufurone analogues.
AB  - A divergent approach to the 7-oxa (-)-muricatacin analogue 2, the corresponding
      (+)-enantiomer ent-2 and the furanolactone 3 is reported starting from D-xylose.
      The resulting lactones have shown a potent and selective in vitro cytotoxicity
      against certain human neoplastic cell lines.

PMID- 16891044
TI  - Cryptic B-cell epitope identification through informational analysis of protein
      sequences.
AB  - A comparison of the location of B-cell epitopes and information structure (IS) of
      protein sequences was attempted. Analysis of 62 known B-cell epitopes located in
      five different proteins showed that they concentrated in IS sites with increased
      degree of information coordination. Based on the analysis of IS six peptides from
      two proteins were selected and produced in a recombinant form as yeast virus-like
      particles (VLPs). Immunization of mice with recombinant VLP-peptides has induced
      the production of IgG capable of recognizing full-length antigens. This result
      suggests that the analysis of IS of proteins can be useful in the selection of
      peptides possessing cryptic B-cell epitope activity.

PMID- 16891045
TI  - Organohalogen compounds in human breast milk from Republic of Buryatia, Russia.
AB  - Human breast milk samples collected during 2003/04 in Buryatia, a Russian
      autonomous republic, were analyzed in order to assess human exposure to
      organohalogen compounds including organochlorine pesticides, polychlorinated
      biphenyls (PCBs), and polybrominated diphenyl ethers (PBDEs). When compared with
      available worldwide data, levels of HCB (23-880 ng/g lipid wt.), PCBs (69-680
      ng/g lipid wt.), and HCHs (100-3700 ng/g lipid wt.) were relatively high,
      indicating elevated human exposure to these organochlorines (OCs) in Buryatia. In
      contrast to OCs, PBDE concentrations were low (0.46-1.7 ng/g lipid wt.). Out of
      14 BDE congeners analyzed, BDE-28, BDE-47, BDE-100, BDE-153, BDE-197, and BDE-207
      were detected. Estimated daily intakes (EDIs) of HCHs, HCB, CHLs, and PCBs by
      infants solely from human milk for 100%, 43%, 34%, and 17% of the samples,
      respectively, exceeded guideline thresholds. Although high EDIs raise concern for
      possible toxic effects of OCs, women in Buryatia are recommended to breastfeed
      due to numerous advantages of breastfeeding for mother and child.

PMID- 16891047
TI  - Assessment of the health status and risk factors of Kham Tibetan pastoralists in
      the alpine grasslands of the Tibetan plateau.
AB  - The health status of Tibetan herders in the Sanjiangyuan region of the Tibetan
      Plateau, in southwest Qinghai Province, is assessed in this paper. The field
      study was conducted in 2002 in the context of a broader community development and
      research framework, the ultimate goal of which is to achieve an effective region
      specific programme of preventative health care and training for Tibetan
      pastoralists. Specifically, the authors analysed the impact of a number of
      potentially health-related environmental and lifestyle risk factors on self
      reported health indicators, with a special emphasis on mother and child health.
      Several health status indicators were used, including a general morbidity index
      and a measurement of functional incapacity due to illness in the sample
      households. Maternal and child health findings were alarming with high rates of
      miscarriage and infant loss, with no traditional midwives to assist in pregnancy
      and delivery. Preventable childhood illnesses were also common. Other
      debilitating diseases included hepatitis, tuberculosis, arthritis (gout), gall
      bladder disease, peptic ulcers and back pain. Finally, binary logistic regression
      analysis showed a significant link between general morbidity and the time it
      takes to obtain water. The survey findings, validated by the focus groups,
      indicate a real need for increased accessibility and quality of health service
      provision to women and men and effective preventative health strategies.

PMID- 16891046
TI  - The occurrence and removal of selected pharmaceutical compounds in a sewage
      treatment works utilising activated sludge treatment.
AB  - Pharmaceutical substances have been detected in sewage effluents as well as
      receiving waters in many parts of the world. In this study, the occurrence and
      removal of a number of drug compounds were studied within a large sewage
      treatment plant in the south of England. Samples were processed using solid phase
      extraction and analysed using gas chromatography-mass spectrometry (GC-MS). The
      results demonstrate that ibuprofen, paracetamol, salbutamol and mefenamic acid
      were present in both the influent and effluent of the works while propranolol-HCl
      was not found above the limit of quantification in any sample. Elimination rates
      were circa 90% for each compound but several hundred nanograms per litre were
      still present in the final effluent.

PMID- 16891048
TI  - Try to be healthy, but don't forgo your masculinity: deconstructing men's health
      discourse in the media.
AB  - The emergence of discourse around men's health has been evident now for at least
      10 years across academic, policy and media texts. However, recent research has
      begun to question some of the assumptions presented concerning masculinity and
      men's health, particularly within popular media representations. The present
      paper builds on previous research by interrogating the construction of men's
      health presented in a recent special feature of a UK national newspaper (The
      Observer, November 27, 2005). The dataset was subjected to intensive scrutiny
      using techniques from discourse analysis. Several inter-related discursive
      patterns were identified which drew upon essentialist notions of masculinity,
      unquestioned differences between men and women, and constructions of men as
      naive, passive and in need of dedicated help. The implications of such
      representations for health promotion are discussed.

PMID- 16891049
TI  - Risk assessment of substances that are both genotoxic and carcinogenic report of
      an International Conference organized by EFSA and WHO with support of ILSI
      Europe.
AB  - The European Food Safety Authority (EFSA) and the World Health Organization
      (WHO), with the support of the International Life Sciences Institute, European
      Branch (ILSI Europe), organized an international conference on 16-18 November
      2005 to discuss how regulatory and advisory bodies evaluate the potential risks
      of the presence in food of substances that are both genotoxic and carcinogenic.
      The objectives of the conference were to discuss the possible approaches for risk
      assessment of such substances, how the approaches may be interpreted and whether
      they meet the needs of risk managers. ALARA (as low as reasonably achievable)
      provides advice based solely on hazard identification and does not take into
      account either potency or human exposure. The use of quantitative low-dose
      extrapolation of dose-response data from an animal bioassay raises numerous
      scientific uncertainties related to the selection of mathematical models and
      extrapolation down to levels of human exposure. There was consensus that the
      margin of exposure (MOE) was the preferred approach because it is based on the
      available animal dose-response data, without extrapolation, and on human
      exposures. The MOE can be used for prioritisation of risk management actions but
      the conference recognised that it is difficult to interpret it in terms of health
      risk.

PMID- 16891050
TI  - Molecular and systems mechanisms of memory consolidation and storage.
AB  - Until recently, memory consolidation and storage had been traditionally viewed as
      a permissive process derived from learning-activated molecular signaling cascades
      which include activations of the NMDA receptors, CaMKII, PKC, PKA and other
      kinases, new protein synthesis and CREB-mediated gene expression, and subsequent
      structural modifications at certain synapses. However, the time-scale of such a
      cascade is incompatible with the timescale of systems-level memory consolidation.
      Furthermore, increasing evidence suggests that synaptic proteins and structures
      are not stationary, but rather are highly dynamical and subjected to metabolic
      turnovers which would cause drift in synaptic efficacy and subsequently unstable
      neural circuits. Recent experiments using inducible gene- or protein-knockout
      techniques reveal that post-learning NMDA receptor and CaMKII reactivations are
      required for the systems-level consolidation of both hippocampal-dependent and
      hippocampal-independent memories. Furthermore, the reactivations of the NMDA
      receptors are also necessary for the long-term storage of old memories in the
      neural circuits. Therefore, the NMDA receptor reactivation-mediated synaptic
      reentry reinforcement (SRR) process may represent the unifying cellular mechanism
      in linking the consolidation and storage of long-term memories from the molecular
      level to the systems-level.

PMID- 16891051
TI  - Long-term results of tension-free vaginal tape (TVT) for the treatment of female
      urinary stress incontinence.
AB  - OBJECTIVES: Prospective evaluation of outcome and complications over a 5-year
      period post-treatment of urinary stress incontinence by TVT, and comparison of
      our results with the reference studies. MATERIALS AND METHODS: About 94 patients
      were treated for urinary stress incontinence only by one TVT procedure (single
      surgical procedure), between April 1997 and December 1998; 68% of patients
      presented pure urinary stress incontinence and 32% mixed incontinence. We found
      also a 25.5% rate of sphincter deficiency (UCP < 20 cm H(2)O) in this cohort.
      Patients were evaluated after 5 years: 52 complete evaluations (clinical, flow
      measurement with measurement of post-mictional residue, 24h PAD-test, quality of
      life questionnaire), 30 complete telephone interviews, 12 lost to follow-up (2
      patients deceased). RESULTS: About 87% of the patients had a 5-year follow-up.
      The success rate was 79.2% overall (84.5% for the pure urinary stress
      incontinence and 67% for the mixed incontinence cases), and 72.2% for the cases
      of associated sphincter deficiency. We had only a 13% rate of patients lost to
      follow-up. More than half of the urinary urgency cases were treated successfully,
      however with a less satisfactory outcome in cases of bladder instability. The
      urodynamic exploration appeared to reveal that TVT caused dysuria: 52% of
      patients had a maximum flowrate below 15 ml/s, but the quality of life was
      improved, with a 95% rate of satisfaction without functional problems. We
      observed no late complications such as vaginal erosion or rejection of the
      prolene; the de novo syndrome was rare, with 8.5% of urinary frequency, 6% of
      urinary urgency and only 5.7% of invalidating dysuria. We saw no cases of pelvic
      floor disease after TVT treatment. DISCUSSION: Our casuistry results are
      comparable with the reference studies by Scandinavian authors, Rezapour and
      Ulmsten, confirming the long-term success of the TVT procedure. Concerning the
      apparently elevated rates of post-TVT dysuria found by urodynamic exploration, a
      distinction has to be drawn between post-TVT urinary problems (frequent but
      oligosymptomatic), and true, severe dysuria (rare). However, "dysuria" in the
      broad sense did not affect the patients' quality of life, and is a reminder of
      the absolute necessity of meticulous compliance with the correct surgical
      techniques. CONCLUSION: Treatment of urinary incontinence by TVT is a reliable,
      mini-invasive, reproducible technique, almost suitable for outpatients, with no
      serious complications; it is inexpensive and very successful, including in
      complicated cases such as sphincter deficiency. All the recent data confirms,
      with this 5-year follow-up, that the TVT procedure is comparable to the
      previously gold standard, the Burch colposuspension.

PMID- 16891053
TI  - Capturing fugitive methane emissions from natural gas compressor buildings.
AB  - Fugitive methane emissions account for about 50% of the greenhouse gas (GHG)
      emissions from the Canadian conventional oil and gas sector. Sources include
      leaks in natural gas transmission facilities such as pipelines and compressor
      stations. There are three sources of methane emissions in a compressor station.
      The first is emissions resulting from incomplete combustion in the engine; the
      second is leaks in valves, flanges and other equipment in the building; and the
      third results from instrument venting. Fugitive methane emissions may be in low
      concentration relative to air, and thus cannot be destroyed by conventional
      combustion (below flammability limits of about 5-16%). The present study
      investigates the feasibility of capturing methane emissions from a compressor
      station. Computer modelling of the flow patterns of lean methane emissions inside
      the building is used to show the influence of doors, vents and leak location.
      Simulations show that for a typical building most fugitive methane exits through
      the ridge vent provided that the main doors remain closed. When the extraction
      rate through the ridge vent is controlled, the methane concentration is at
      acceptable levels for destruction in a catalytic flow reverse reactor, that is,
      in the range of 0.1-1% by volume.

PMID- 16891052
TI  - Influence of tumor necrosis factor-alpha on estradiol, progesterone, insulin-like
      growth factor-II, and insulin-like growth factor binding protein-1, 2, and 3 in
      cultured human luteinized granulosa cells.
AB  - OBJECTIVE: The objective was to investigate the influence of tumor necrosis
      factor (TNF)-alpha on estradiol, progesterone, insulin-like growth factor (IGF)
      II, and insulin-like growth factor binding protein (IGFBP)-1, 2, and 3 in
      cultured human luteinized granulosa cells. STUDY DESIGN: Human luteinized
      granulosa cells were obtained from follicular fluid by transvaginal oocyte
      aspiration from infertile patients undergoing controlled ovarian hyperstimulation
      (COH) for in vitro fertilization (IVF). The cells were cultured for 72 h with TNF
      alpha at concentrations of 1.0, 10.0, and 100.0 ng/ml. The cells not treated with
      TNF-alpha served as controls. Radioimmunoassay (RIA) and reverse transcription
      polymerase chain reaction (RT-PCR) were used to examine the influence of TNF
      alpha on estradiol, progesterone, IGF-II, and IGFBP-1, 2, and 3. Results were
      analyzed using the Kolmogorov-Smirnov test and analysis of variance (ANOVA).
      Statistical significance was defined as p<0.05. RESULTS: The concentrations of
      progesterone seemed to decrease as the concentrations of TNF-alpha increased and
      the concentration of progesterone in the 100.0 ng/ml TNF-alpha group was
      significantly lower than that in the control and other TNF-alpha groups. The
      expressions of IGF-II mRNA in the 10.0 and 100.0 ng/ml TNF-alpha groups were
      significantly lower than that in the control group. The expressions of IGFBP-2
      mRNA seemed to be decreased in the 10.0 and 100.0 ng/ml TNF-alpha groups compared
      with that in the control group, but there were no statistical significances.
      CONCLUSION: TNF-alpha may play a role as a regulator of human ovarian physiology
      by modulating the IGF systems in luteinized granulosa cells.

PMID- 16891054
TI  - Education campaigns to reduce stormwater pollution in commercial areas: do they
      work?
AB  - A monitoring and evaluation program was undertaken, involving six different
      styles of evaluation to determine whether a low-cost, eight month education
      campaign that operated within a small commercial district was successful at
      changing people's behavior and reducing stormwater litter loads. This project
      also tested newly developed guidelines for monitoring and evaluating all types of
      non-structural stormwater quality best management practices (BMPs). The project
      evaluated: the extent and quality of the campaign's implementation; the degree to
      which it changed the awareness, attitudes, self-reported behavior and actual
      behavior of merchants and the public; and the nature of changes in stormwater
      litter loads. Overall, the education campaign produced mixed results, with the
      net result being modestly positive. Specifically, it was: unsuccessful at
      significantly influencing the knowledge or attitudes of merchants or the public;
      modestly successful at influencing the behavior of merchants and the public; and
      modestly successful at reducing litter loads in stormwater. At a theoretical
      level, the project highlights how using different 'styles' of BMP evaluation can
      help to build a more complete picture of a BMP's performance. At a practical
      level, the project helped to improve the monitoring and evaluation guidelines and
      produced evidence-based design guidelines for future campaigns that aim to reduce
      littering in commercial areas.

PMID- 16891055
TI  - Novel expression and functional role of ghrelin in chicken ovary.
AB  - Ghrelin has recently emerged as pleiotropic regulator of a wide array of
      endocrine and non-endocrine functions. The former likely includes the control of
      gonadal function, as expression of ghrelin and its putative receptor, the GH
      secretagogue receptor type 1a (GHS-R1a), has been described in mammalian gonads,
      and direct effects of ghrelin in the control of testicular secretion and cell
      proliferation have been reported. Yet, the expression and/or functional role of
      ghrelin in gonads from non-mammalian species remain to be analyzed. The present
      study aimed to evaluate the expression of ghrelin and GHS-R genes in the chicken
      ovary, and to assess the potential involvement of ghrelin in the direct control
      of chick ovarian function. To this end, RT-PCR assays for ghrelin and GHS-R1a
      mRNAs were performed in ovarian tissue, and cultures of chicken ovarian cells
      were conducted in the presence of increasing doses (1, 10 or 100 ng/ml) of the
      ghrelin analog, ghrelin 1-18. Our results demonstrate that both ghrelin and GHS
      R1a mRNAs are expressed in chick ovarian tissue. Moreover, challenge of ovarian
      granulosa cells with ghrelin 1-18 was able to induce markers of proliferation
      (i.e. expression of both PCNA and cyclin), and to modulate markers of apoptosis
      (i.e. decreased expression of caspase-3, bax, bcl-2 and TUNEL-positive cells).
      Moreover, ghrelin 1-18 increased the expression of PCNA, cyclin, bax and p53 in
      cultures of ovarian follicular fragments, where it also stimulated the release of
      progesterone, estradiol, arginine-vasotocin (AVT) and IGF-I, but not of
      testosterone. In conclusion, our study provides novel evidence for the gonadal
      expression of the genes encoding ghrelin and its cognate receptor in a non
      mammalian species, i.e. the chicken ovary, and unravels the potential involvement
      of this newly discovered molecule in the control of key gonadal functions in the
      chick, such as proliferation, apoptosis, and hormone release.

PMID- 16891056
TI  - Changes in plasma vascular endothelial growth factor, angiopoietins, and their
      receptors following surgery for breast cancer.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF), a major angiogenic growth
      factor, is involved in the pathogenesis of cancer. Plasma VEGF is raised in
      breast cancer and falls after successful surgery. Less is known about
      angiopoietins 1 and 2 (Ang-1, Ang-2). All three growth factors act on cells via
      receptors; Flt-1 for VEGF and Tie-2 for the angiopoietins. Cancer is also marked
      by abnormalities in platelet activation (marked by soluble P selectin) and
      inflammation (interleukin-6 [IL6]). We hypothesised altered plasma Ang-1, Ang-2,
      Flt-1 and Tie-2 in breast cancer that would normalize after 3 and 12 months
      treatment (i.e., surgery plus chemo/radiotherapy). METHODS: Baseline venous blood
      was obtained from 40 women with breast cancer and 30 age-matched women with
      benign breast disease (BBD) also requiring surgery. Samples were taken again 3
      months and 1 year later. Soluble P selectin, IL6, VEGF, Ang-1, Ang-2, Flt-1 and
      Tie-2 were measured in citrated plasma by ELISA. RESULTS: Women with breast
      cancer had raised VEGF (7-fold), Ang-1 (50% higher) and Tie-2 (2-fold), but lower
      Flt-1 (to 26%), compared to the BBD women that broadly correlated with markers of
      platelet activation and inflammation. A level of Tie-2 or VEGF >95th percentile
      of the BBD group correctly identified 68% and 52% of the women with breast
      cancer. After 3 months of treatment, VEGF and Ang-1 normalized (as did IL6 and
      soluble P selectin) but Tie-2 was significantly lower only after 1 year. There
      were no significant changes in the women with BBD. CONCLUSIONS: Treatment for
      breast cancer (surgery followed by chemotherapy and/or radiotherapy) is effective
      in reducing plasma VEGF, Tie-2 and Ang-1. These may be linked pathogenically with
      coagulation and inflammation.

PMID- 16891057
TI  - Severe weight loss in lambs infected with Giardia duodenalis assemblage B.
AB  - An outbreak of giardiasis was observed in a sheep farm in Central Italy. Infected
      lambs (30-90 days of age) showed a malabsorption syndrome, decreased weight gain
      and impairment in feed efficiency. The most relevant clinical sign was the
      excretion of malodorous and poorly formed faeces, whereas diarrhoea was rarely
      observed in the flock. Laboratory investigations revealed the presence of Giardia
      in affected animals, while no other significant viral, bacterial or parasitic
      pathogens were identified in faeces or tissue samples. A mild to severe
      infiltrative enteritis with eosinophils, lymphocytes and plasma cells was
      detected in histological sections of the gut. Giardia parasites collected from
      duodenal aspirates were typed as Giardia duodenalis Assemblage B, by PCR
      amplification and sequencing of the TPI gene. Treatment with fenbendazole at a
      dose of 10mg/kg for 3 consecutive days, successfully cleared the infection. These
      results show that G. duodenalis can cause significant economic losses in sheep
      farming.

PMID- 16891058
TI  - Strain dependence of the cell wall-damage induced stimulon in Staphylococcus
      aureus.
AB  - The vancomycin stress induced transcriptome of the methicillin susceptible
      Staphylococcus aureus (MSSA) strain Newman was determined by microarray analysis.
      Subsets of the induced ORFs corresponded to those previously reported to be
      induced by vancomycin in the methicillin resistant S. aureus (MRSA) strains N315
      and JH1, and/or by other cell wall active antibiotics in RN450; while other ORFs
      appeared to be induced strain specifically in Newman. Northern analyses showed
      that the induction pathway for several of the ORFs appeared to be altered in a
      number of clinical NARSA isolates. Induction was found to be dependent on
      inhibitory concentrations of antibiotics.

PMID- 16891060
TI  - gamma-Glutamyltransferase is a promising biomarker for cardiovascular risk.
AB  - Oxidative stress plays a crucial role in a variety of clinical settings of
      atherogenesis, and mediates many pathways linked to atherosclerosis and
      inflammation. gamma-Glutamyltransferase (GGT), an enzyme responsible for the
      extracellular catabolism of antioxidant glutathione, may directly take part in
      atherogenesis and evolve as a potential biochemical risk indicator of
      cardiovascular morbidity and mortality. Classically, GGT has been thought of as a
      diagnostic tool for hepatobiliary disorders and alcohol abuse. More recently,
      growing body of data points out that serum GGT levels can aid detection of
      individuals at high risk for subsequent cardiovascular events, and thus have an
      application in primary and secondary prevention of cardiovascular disease.
      Although several investigations have shown that some drugs are effective in
      decreasing both serum lipids and GGT, and concomitantly the incidence of
      subsequent cardiovascular events; large-scale randomized trials are required to
      explore this impact directly. Based on current experimental and epidemiological
      studies, we postulate here that GGT present in the serum, even within its
      laboratory reference intervals regarded as physiologically normal, is a promising
      biomarker for cardiovascular risk.

PMID- 16891059
TI  - Brainstem glycinergic neurons and their activation during active (rapid eye
      movement) sleep in the cat.
AB  - It is well established that, during rapid eye movement (REM) sleep, somatic
      motoneurons are subjected to a barrage of inhibitory synaptic potentials that are
      mediated by glycine. However, the source of this inhibition, which is crucial for
      the maintenance and preservation of REM sleep, has not been identified.
      Consequently, the present study was undertaken to determine in cats the location
      of the glycinergic neurons, that are activated during active sleep, and are
      responsible for the postsynaptic inhibition of motoneurons that occurs during
      this state. For this purpose, a pharmacologically-induced state of active sleep
      (AS-carbachol) was employed. Antibodies against glycine-conjugated proteins were
      used to identify glycinergic neurons and immunocytochemical techniques to label
      the Fos protein were employed to identify activated neurons. Two distinct
      populations of glycinergic neurons that expressed c-fos were distinguished. One
      population was situated within the nucleus reticularis gigantocellularis (NRGc)
      and nucleus magnocellularis (Mc) in the rostro-ventral medulla; this group of
      neurons extended caudally to the ventral portion of the nucleus paramedianus
      reticularis (nPR). Forty percent of the glycinergic neurons in the NRGc and Mc
      and 25% in the nPR expressed c-fos during AS-carbachol. A second population was
      located in the caudal medulla adjacent to the nucleus ambiguus (nAmb), wherein
      40% of the glycinergic cells expressed c-fos during AS-carbachol. Neither
      population of glycinergic cells expressed c-fos during quiet wakefulness or quiet
      (non-rapid eye movement) sleep. We suggest that the population of glycinergic
      neurons in the NRGc, Mc, and nPR participates in the inhibition of somatic
      brainstem motoneurons during active sleep. These neurons may also be responsible
      for the inhibition of sensory and other processes during this state. It is likely
      that the group of glycinergic neurons adjacent to the nucleus ambiguus (nAmb) is
      responsible for the active sleep-selective inhibition of motoneurons that
      innervate the muscles of the larynx and pharynx.

PMID- 16891061
TI  - The histone deacetylase inhibitor FK228 may have therapeutic usefulness to
      prevent suicidal behaviour via upregulation of the guanosine triphosphatase Rap
      1.

PMID- 16891062
TI  - The relationship between telomerase activity and proliferation in cutaneous
      melanoma.
AB  - Telomerase is a ribonucleoprotein reverse transcriptase which RNA component
      (TERC) and reverse transcriptase (TERT) function together to elongate telomeres.
      If cells are to survive and proliferate indefinitely, telomere preservation is
      essential for the immortalization process. Somatic cells rarely possess TA, but
      over 90% of tumor cells express active telomerase. Increased cell proliferation
      and deregulation of cell cycle occur in human cancers, including cutaneous
      melanoma. The exact nature of links between TA, cell proliferation and apoptosis
      has not been extensively elucidated in cutaneous melanoma. We hypothesize a
      relationship between TA and cutaneous melanoma cell proliferation in a way that
      TA in telomere elongation is only an early event in cell immortalization. The
      telomere elongation makes their proliferation possible and being, at the same
      time, one of its limiting factors. But the TA other than telomere elongation
      (TERC independent) is crucial to initiate or restore melanoma cell proliferation.
      On the other hand, TA in telomere elongation, together with other factors (for
      example TNF), has an active anti-apoptotic role. This way melanoma cells
      overwhelm the apoptotic defense mechanisms, finally resulting in their indefinite
      proliferation. In evaluation of our hypothesis, we suggest thorough studies of
      both telomerase activity and proliferation in cutaneous melanoma on multiple
      checkpoints and targets. We also suggest combined analyses of TA and telomere
      length. This approach seems inevitable since it is obvious that telomerase is no
      longer just for the elongation of telomeres and, to our knowledge, most of the
      studies conducted so far evaluated TA as an expression of a single subunit or
      associated molecule.

PMID- 16891063
TI  - No evidence for interactions between oral anticoagulants and sertraline.

PMID- 16891064
TI  - Diagnosis of Coxiella burnetii-related abortion in Italian domestic ruminants
      using single-tube nested PCR.
AB  - Coxiella burnetii, an obligate intracellular parasite with a worldwide
      distribution, is the causative agent of acute and chronic Q fever in humans.
      Although infection is often unapparent in cattle, sheep and goats, there is
      increasing evidence that C. burnetii infection in these species is associated
      with abortion and stillbirth. This paper describes the introduction of a single
      tube nested PCR protocol for the diagnosis of C. burnetii-related abortion in
      domestic ruminants in Italy. A total of 514 aborted foetuses from cattle (n =
      138) and sheep and goat (n = 376), collected from 301 farms, were analyzed from
      January 2001 to March 2005. Ninety-seven of 514 (18.9%) animals tested PCR
      positive, with 16/138 (11.6%) cattle and 81/376 (21.5%) sheep and goat. Eleven of
      102 (10.8%) farms with reproductive disorders in cattle and 37/199 (18.6%) farms
      with reproductive disorders in sheep and goats were infected with C. burnetii. A
      greater incidence was observed in three of the seven investigated provinces (p <
      0.01), with rates of infected farms of up to 23.8%. Data showed that almost all
      the C. burnetii-related abortions were recorded between October and April (p <
      0.01). These findings suggest that Q fever in humans is largely underestimated in
      Italy, probably because its occurrence is obscured by flu-like symptoms in acute
      forms.

PMID- 16891065
TI  - The corrected blood urea nitrogen predicts the developmental quotient of
      extremely low-birth-weight infants at the corrected age of 36 months.
AB  - BACKGROUND: Currently, there are no nutritional indices to predict cognitive
      function in extremely low-birth-weight (ELBW) infants. OBJECTIVE: To assess the
      neonatal blood urea nitrogen (BUN) values in ELBW infants according to their
      cognitive function at the corrected age of 36 months. METHODS: This was a
      retrospective study that assessed the neonatal factors affecting the
      developmental outcome in two groups "developmental quotient (DQ)> or =80" and
      "DQ<80", the groups were divided based on the DQ at the corrected age of 36
      months. Between 1996 and 1999, 178 ELBW infants born at <28 weeks of gestation
      were admitted to our neonatal intensive care unit (NICU), of these, 32 died. Of
      the surviving 146 infants, 37 infants without any exclusion criteria (that would
      affect the cognitive function and BUN) except the nutritional factor, were
      assessed. Area under the curve (AUC) of corrected BUN (CBUN: BUN x 0.5/serum
      creatinine) from 28 to 84 days of life was used as an index of protein intake.
      RESULTS: No significant differences were observed between the two groups with
      regard to the gestational age, birth weight, Z score of birth weight, and sex.
      However, compared to 15 infants with DQ<80, 22 infants with DQ> or =80 had
      significantly shorter duration of artificial ventilation and O(2)
      supplementation, a higher Apgar score at 5 min, and a higher AUC of CBUN. On
      multiple regression analysis, DQ> or =80 was observed to be significantly
      correlated with the AUC of CBUN (Odd's ratio 1.03, 95% confidence interval: 1.002
      1.06). CONCLUSION: The CBUN level would provide an estimate of adequate protein
      intake and the subsequent development of an ELBW infant.

PMID- 16891066
TI  - Bimoclomol ameliorates mercuric chloride nephrotoxicity through recruitment of
      stress proteins.
AB  - Bimoclomol (BIM), is a stress proteins coinducer, that acts synergistically with
      a mild stressor to activate cytoprotective stress proteins. BIM has been
      successfully utilized in animal models for the treatment of various nervous,
      cardiac and cerebrovascular diseases. Mercuric chloride (HgCl(2)) induces acute
      renal failure in rats by a single dosage. The present in vivo study was conducted
      to assess the efficacy of BIM against acute HgCl(2) nephrotoxicity. At different
      times after BIM and/or HgCl(2) exposure we evaluated renal morphology and the
      localization/abundance of three stress proteins (HSP72, GRP75, HSP60) by electron
      microscopy, immunohistochemistry and Western blot analysis. BIM delivery to rats
      6h before mercury, ameliorated damage to renal ultrastructure, with recovery of
      tubular and mitochondrial membranes 24h after mercury treatment. In rats
      pretreated with BIM prior to HgCl(2) exposure, HSP72 was significantly
      overexpressed in proximal tubules in a time-dependent manner. In contrast, the
      amounts of GRP75 and HSP60 after BIM pretreatment were comparable to the group
      treated with mercury alone, but these stress proteins had translocated to the
      nuclei at 14 and 24h, respectively. These novel findings suggest that BIM
      mitigates HgCl(2) nephrotoxicity in rats through the early recruitment of stress
      proteins in midcortical proximal tubules that are the main renal mercury-targets.

PMID- 16891067
TI  - The induction of CYP1A1 by oltipraz is mediated through calcium-dependent
      calpain.
AB  - The induction of CYP1A1 expression by oltipraz, a synthetic chemo-preventive
      agent, which increases intracellular calcium concentration, has previously been
      shown to result from transcriptional activation of CYP1A1 gene mediated by the Ah
      receptor (AhR), although oltipraz does not bind the receptor. The present study
      investigated the possible mechanisms of oltipraz-induced activation of AhR and
      the subsequent induction of CYP1A1 transcription. Treatment of the human
      metastatic breast cancer cell line MT-2 with oltipraz results in a concentration
      dependent increase in the activity of the calcium-dependent calpain, as measured
      towards the BOC-LM-CMAC fluorescent substrate. This increase in calpain activity
      was coupled with the AhR activation, as evidenced by its nuclear localization and
      increased transcription of CYP1A1 gene. Treatment of cells with calpain specific
      inhibitor MDL 28170 completely blocked the oltipraz-induced nuclear translocation
      of AhR and subsequent CYP1A1 expression. Furthermore, treatment with oltipraz
      resulted in the classical ligand-dependent down-regulation of AhR protein, in a
      concentration dependent manner. The presented data established for the first time
      a mechanism of activating AhR and its transcription of CYP1A1 by oltipraz through
      activation of calcium-dependent calpain.

PMID- 16891068
TI  - Adriamycin release from self-assembling nanospheres of poly(DL-lactide-co
      glycolide)-grafted pullulan.
AB  - Poly(DL-lactide-co-glycolide)-graft pullulan (PuLG) was synthesized to produce a
      hydrophobically modified polysaccharide. Specific pullulan and poly(DL-lactide-co
      glycolide) (PLGA) (abbreviated as PuLG) appeared in the peaks of the PuLG spectra
      on (1)H NMR spectroscopy, suggesting that PLGA was successively grafted to the
      pullulan backbone. PuLG nanospheres have a round shape with a particle size of
      about 75-150 nm. From the fluorescence excitation spectra in a fluorescence probe
      study, the critical association concentration (CAC) values were determined to be
      0.017 g/l for PuLG-1, 0.0054 g/l for PuLG-2, and 0.0047 g/l for PuLG-3. The drug
      contents of the PuLG nanospheres were approximately 20-30% (w/w). As the drug
      contents of PuLG nanospheres increased, the drug release rate from nanospheres
      decreased. The drug release rate from PuLG nanospheres was delayed as the
      molecular weight of PuLG increased. PuLG copolymer with higher graft ratio of
      PLGA showed slower degradation rate rather than that with lower graft ratio.
      Since degradation rate of PuLG was taken over 1 month, drug release was governed
      by diffusion mechanism rather than degradation mechanism.

PMID- 16891069
TI  - Influence of an anti-diabetic foot ulcer formula and its component herbs on
      tissue and systemic glucose homeostasis.
AB  - Complications of diabetes impose major public health burdens worldwide. The
      positive effect of a Radix Astragali-based herbal preparation on healing diabetic
      foot ulcers in patients has been reported. Formula 1 is also referred as the
      'Herbal drink to strengthen muscle and control swelling'. This formula contains
      six Chinese medical herbs, including Radix Astragali, Radix Rehmanniae, Rhizoma
      Smilacis Chinensis, Rhizoma Atractylodis Macrocephalae, Radix Polygoni Multiflori
      Preparata, and Radix Stephania Tetrandrae. Three of these herbs (Radix Astragali,
      Radix Rehmanniae, Rhizoma Atractylodis Macrocephalae) are commonly used in
      different anti-diabetic formulae of Chinese medicine. The objective of the
      current study is to use an interdisciplinary approach to test the hypothesis that
      Formula 1 and its components influence tissue and systemic glucose homeostasis.
      In vitro and in vivo models have been established including: (1) glucose
      absorption into intestinal brush border membrane vesicles (BBMV); (2)
      gluconeogenesis by H4IIE hepatoma cells; (3) glucose uptake by 3T3-L1 adipocytes
      and Hs68 skin fibroblasts; (4) normalization of glycaemic control in a diabetic
      rat model. The results of in vitro studies indicated that all herbal extracts can
      modify cellular glucose homeostasis. Since Formula 1 and Rhizoma Smilacis
      Chinensis extracts demonstrated potent effects on modifying glucose homeostasis
      in multiple tissues in vitro, they were further studied for their anti-diabetic
      activities in vivo using a streptozotocin (STZ)-induced diabetic rat model. The
      results showed that Formula 1 and Rhizoma Smilacis Chinensis extracts did not
      significantly improve oral glucose tolerance or basal glycaemia in diabetic rats.
      In conclusion, the anti-diabetic foot ulcer Formula 1 contains ingredients active
      in modifying tissue glucose homeostasis in vitro but these biological activities
      could not be associated with improved glycaemic control of diabetes in vivo.

PMID- 16891070
TI  - Computed tomography as routine in connection with medico-legal autopsies.
AB  - CT-scanning as routine examination before medico-legal autopsy was introduced at
      the Institute of Forensic Medicine in Copenhagen, Denmark, in December 2002. The
      present series comprises of 525 medico-legal examinations performed in the year
      2003. The purpose is to determine the value of CT-scanning prior to the post
      mortem examination. All findings, CT- as well as patho-anatomic findings - more
      than 4000 - were registered in a database. To increase the clearness, the
      findings are divided in accordance to regions such as head, thorax, abdomen,
      pelvis, extremities and vessels and the CT-findings are compared to the patho
      anatomic findings, with the purpose to estimate the advantages and disadvantages
      with the two types of examination. The preliminary results show, that the CT
      scanner is superior when it comes to detection of extremity fractures. The
      scanner has ability in detecting hemorrhages and hematomas, especially,
      intracranial.

PMID- 16891071
TI  - Two fatal cases of selenium toxicity.
AB  - Two patients, a 36-year-old female and a 36-year-old male, separately experienced
      new onset nausea, vomiting, diarrhea, abdominal pain, muscle weakness and pallor.
      Over a period of 14-16 h these symptoms continue and progress to include
      hypotension refractory to therapy, pulmonary edema and cardiovascular collapse.
      Autopsies show hemorrhagic pulmonary edema, splenomegaly and lack of anatomical
      cause for sudden death. Postmortem analysis, in one case post-embalming and
      exhumation, revealed elevated selenium concentrations and a determination of the
      cause of death. These two cases present several important features associated
      with selenium toxicity, two of which are previously unreported: (1) selenium as a
      potential homicidal agent, (2) the toxidrome and time frame of selenium toxicity,
      (3) selenium determination in exhumed, embalmed tissues, (4) postmortem urinary
      selenium concentration, and (5) decrease in tissue concentrations over time.

PMID- 16891072
TI  - Triad-related homicides in Hong Kong.
AB  - This study provides an overview of the first systematic research on triad-related
      homicide in a Chinese society. In the 10-year period from 1989 to 1998, 11.9% of
      all homicides or a total of 95 triad-related homicides were extracted from the
      Hong Kong Homicide Monitoring Database. These events resulted in 124 victims
      (13.2 percent of all victims) and involved 526 known offenders. Triad homicides
      were classified into various types based on different combinations of
      circumstances, motivation, and outcomes including unintended outcomes.

PMID- 16891073
TI  - Using morphometric and analytical techniques to characterize elephant ivory.
AB  - There is a need to characterize Asian elephant ivory and compare with African
      ivory for controlling illegal trade and implementation of national and
      international laws. In this paper, we characterize ivory of Asian and African
      elephants using Schreger angle measurements, elemental analysis {X-ray
      fluorescence (XRF), inductively coupled plasma-atomic emission spectroscopy (ICP
      AES), and inductively coupled plasma-mass spectroscopy (ICP-MS)} and isotopic
      analysis. We recorded Schreger angle characteristics of elephant ivory at three
      different zones in ivory samples of African (n=12) and Asian (n=28) elephants.
      The Schreger angle ranged from 32 degrees to 145 degrees and 30 degrees to 153
      degrees in Asian and African ivory, respectively. Elemental analysis (for Asian
      and African ivory) by XRF, ICP-AES and ICP-MS provided preliminary data. We
      attempted to ascertain source of origin of Asian elephant ivory similarly as in
      African ivory based on isotopes of carbon, nitrogen and strontium. We determined
      isotopic ratios of carbon (n=31) and nitrogen (n=31) corresponding to diet and
      rainfall, respectively. Reference ivory samples from five areas within India were
      analyzed using collagen and powder sample and the latter was found more suitable
      for forensic analysis. During our preliminary analysis, the range of delta13C
      values (-13.6+/-0.15 per thousand and -25.6+/-0.15 per thousand) and delta15N
      values (10.2+/-0.15 per thousand and 3.5+/-0.15 per thousand) were noted.

PMID- 16891074
TI  - Accumulation of oxidative damage during replicative aging of the yeast
      Saccharomyces cerevisiae.
AB  - Comparison of senescent yeast obtained by the "baby machine" technique with 2-day
      old stationary phase cells revealed decreased activities of glutathione
      reductase, glutathione S-transferase, glutathione peroxidase and alcohol
      dehydrogenase, reduction of total antioxidant capacity, protein glycation and
      accumulation of products of oxidative damage: protein carbonyls and DNA damage
      assessed by augmented content of 8-oxoguanine and increased tail momentum of
      cellular DNA in the comet assay. These results are consistent with a role for
      oxidative damage during replicative senescence of Saccharomyces cerevisiae.

PMID- 16891075
TI  - Decreased CYP3A2 expression and activity in senescent male Wistar rats: is there
      a role for HNF4alpha?
AB  - The effect of ageing on CYP3A2, a male specific isoform, was examined in adult (9
      months) and senescent (24 months) male rats. A significant decrease (65%) of
      CYP3A2-related activity (midazolam oxidation) was observed in all senescent rats.
      Half of these rats still express CYP3A2 suggesting that decreased activities in
      these rats are due to post-translational modifications. The other senescent male
      rats did not express CYP3A2 anymore, indicating an impairment of transcription.
      These transcriptional modifications are due to the previously shown continuous
      secretion of GH in senescent male rats. GH also regulates HNF4alpha, a hepatocyte
      nuclear factor, essential for the basal transcriptional activation of the CYP3A2
      gene. In senescent rats, a drastic reduction (76%) of HNF4alpha protein content
      and a decrease in DNA binding activity were observed. When these parameters were
      assessed in male and female rats of the same age (3 months), a higher HNF4alpha
      DNA binding activity and a higher HNF4alpha protein content (38%) were observed
      in female rats. Our results show that in male senescent rats (1) the decrease of
      HNF4alpha is not consistent with the continuous secretion of GH, and (2) the
      suppression of CYP3A2 expression is not dependent to the HNF4alpha binding
      activity.

PMID- 16891076
TI  - Distinct genetic influences on locomotor senescence in Drosophila revealed by a
      series of metrical analyses.
AB  - Decline of locomotor function is a prominent feature of aging in most species. We
      previously described a series of metrical analyses for quantifying functional
      declines associated with aging. Here, we have applied these metrics to elucidate
      differences in the nature of locomotor senescence between Drosophila cohorts from
      four different genetic backgrounds (Canton-S, Oregon-R, Samarkand and Lausanne-S)
      and two long-lived mutant strains, Indy(206) and chico(1). These analyses
      demonstrate that senescence of locomotor function in Oregon-R and Canton-S
      proceeds more rapidly than in Samarkand and Lausanne-S flies. Our analyses also
      show that while chico(1) and Indy mutants both exhibit attenuated locomotor
      declines, the impact of chico loss of function on locomotor senescence is
      substantially greater. Our studies illustrate how important differences in
      functional senescence characteristics can be unveiled by in-depth analysis on
      functional senescence data sets.

PMID- 16891077
TI  - Whole genome RNAi screens for increased longevity: important new insights but not
      the whole story.
AB  - This article discusses the pros and cons of using RNAi screening to identify
      longevity genes in Caenorhabditis elegans. The discussion will focus on the
      results of two large-scale longevity RNAi screens that were recently published.
      The two screens revealed largely non-overlapping sets of candidate longevity
      genes. The possible reasons for such differences and their implications will be
      discussed.

PMID- 16891078
TI  - Comparison of the femoral neck bone density, quantitative ultrasound and bone
      density of the heel between dominant and non-dominant side.
AB  - Our study was initiated to evaluate whether there are differences between the two
      sides, depending on hand dominance, in densitometry values and quantitative
      ultrasound parameters (QUS) of the lower limb. One hundred and six women and 44
      men were involved. The hand dominance was determined by interview. The bone
      mineral density (BMD) of the left and the right femoral necks and the calcanei
      were measured by dual-energy X-ray absorptiometry (DXA). The QUS examination
      consisted of measuring the attenuation (BUA), the speed of the ultrasound (SOS)
      and quantitative ultrasound index (QUI) transversing the left and right calcanei.
      The density of the neck of femur of the non-dominant side did not differ from
      that of the dominant side. On the other hand, BMD, BUA and the QUI of the
      calcaneus were higher on the non-dominant side in both genders (p<0.05 for each
      parameter). No similar differences were seen for the SOS values. Our study has
      confirmed the side-to-side differences of the calcaneus in both genders, lower
      values were found on the dominant side. No similar differences were seen on the
      femur. The AUC values seemed to be higher on the dominant side, however, these
      differences were not strictly significant. In the case of peripheral site (heel)
      measurements, the practical significance of our observations is that they raise
      the possibility of performing peripheral DXA and QUS examinations of the
      calcaneus on the dominant side of the patient according to handedness.

PMID- 16891079
TI  - CT-guided bone biopsy: Initial experience with a commercially available hand held
      Black and Decker drill.
AB  - PURPOSE: To describe the use of a simple commercially available Black and Decker
      hand based drill in performing CT-guided bone biopsies. MATERIALS AND METHODS:
      Three international institutions were enrolled in the study. In each centre, a
      fellowship trained musculoskeletal radiologist directed the assessment of a hand
      based commercial drill for performing CT-guided bone biopsies. A specially
      designed component was engineered which allowed the connection of a standard bone
      biopsy set to a commercial drill. The component was distributed to the three
      centres involved. Over a 3-year period, data from all three institutions was
      collected. Information regarding technical success, diagnostic data and
      complication rates were all collated to assess the technical feasibility of this
      technique. RESULTS: In total 68 patients underwent bone biopsy using a hand held
      commercial drill. Technical success was achieved in 65 patients. Diagnostic
      material was obtained in 53 patients. Non-diagnostic material was obtained in 12
      patients. Five out of the 12 patients with non-diagnostic material had repeat
      biopsies with diagnostic material obtained in 2 of these. No major complications
      occurred in any patient. CONCLUSION: CT-guided bone biopsy using a hand held
      commercial drill has a technically high success rate with minimal complications.

PMID- 16891080
TI  - The use of coronary stent in hepatic artery stenosis after orthotopic liver
      transplantation.
AB  - PURPOSE: This retrospective study was undertaken to evaluate the effectiveness of
      coronary stent placement in hepatic artery stenosis after orthotopic liver
      transplantation (OLT). MATERIALS AND METHODS: Of 430 consecutive adult orthotopic
      liver transplant recipients between November 2003 and September 2005, 17 had
      hepatic artery stenosis (HAS). Fourteen of them underwent coronary stent
      placement in the HAS. The technical results, complications, hepatic artery
      patency and clinical outcome were reviewed. RESULTS: Technical and immediate
      success was 100%. After a mean follow-up of 159.4 days (range, 9-375 days), all
      patients obtained patent hepatic arteries except 2 patients occurred hepatic
      artery restenoses at 26 and 45 days after stent placement, respectively. Kaplan
      Meier curve of patency showed cumulated stent patency at 3, 6, and 12 months of
      78%, 58% and 45%, respectively. During the follow-up, 8 patients survived, 5 died
      of septic multiple-organ failure, 1 received retransplantation because of
      refractory biliary infection. Hepatic artery dissection induced by a guiding
      catheter occurred in one patient and was successfully treated with a coronary
      stent. CONCLUSION: Hepatic artery stenosis after OLT can be successfully treated
      with coronary stent placement with low complication rate and an acceptable 1-year
      hepatic artery patency rate.

PMID- 16891081
TI  - Columnar cell lesions of the breast: mammographic and US features.
AB  - OBJECTIVES: Columnar cell lesions are being encountered with increasing frequency
      in breast biopsies performed. The purpose of our study was to determine whether
      columnar cell lesions of the breast have any distinctive imaging characteristics.
      MATERIALS AND METHODS: We retrospectively reviewed our institutional database for
      all records of breast pathology obtained in a 17-month period. Columnar cell
      lesion was diagnosed in 53 lesions and 12 of these 53 lesions contained columnar
      cell lesions as the sole histopathologic findings. These 12 lesions in nine
      patients made up our study population. They included columnar cell change (n=4),
      columnar cell hyperplasia (n=5), and columnar cell hyperplasia with atypia (n=3).
      RESULTS: All nine patients underwent mammography and sonography within 1 month of
      each other. Of the mammograms in nine patients, nine lesions (75%) appeared as
      clustered amorphous or indistinct (n=5), fine pleomorphic (n=3), or round (n=1)
      microcalcifications. The tenth lesion showed a focal mass without
      microcalcifications and the remaining two lesions showed no abnormal findings. At
      sonography, not-circumscribed masses were depicted in six lesions and
      microcalcifications were visible in four lesions, of which three lesions were
      concurrent with masses. There were no sonographically focal lesions in the
      remaining five. Overall 11 lesions were classified as BI-RADS category 4 (92%)
      and one as category 3. Of the three lesions with atypia, two were classified as
      category 4a and one was classified as category 4c, and they showed no distinct
      imaging appearance from those without atypia. CONCLUSION: Columnar cell lesions
      usually present as nonpalpable, clustered indeterminate or suspicious
      microcalcifications on mammography. They are indistinguishable from other causes
      of suspicious microcalcifications such as atypical ductal hyperplasia or ductal
      carcinoma in situ and require needle biopsy or excisional biopsy for diagnosis.

PMID- 16891083
TI  - Pharmacotherapy for patients undergoing carotid stenting.
AB  - Stroke is the second most common cause of death worldwide [Murray CJ, Lopez AD.
      Mortality by cause for eight regions of the World: Global Burden of Disease
      Study, Lancet 1997;349:1269-76. [1]] and remains one of the most common and
      disabling neurological disorders, particularly in the elderly. Survivors of
      stroke remain at high risk for developing further vascular events including
      recurrent strokes, myocardial infarction and vascular deaths. Treatment
      modalities for such patients include life style modifications, drug therapy and
      where applicable, surgical or endovascular intervention. Carotid artery disease
      is implicated in 20-30% of the population as the aetiology for stroke [De Bakey
      ME. Carotid endarterectomy revisited, J Endovasc Surg 1996;3:4. [2]]. This
      article examines the pharmacotherapy for patients undergoing carotid stenting.
      This will be divided into best medical therapy for these patients, and is the
      same as that that should be given to all patients following transient ischaemic
      attack (TIA) or stroke. It will provide a concise description of the safety
      profile, dosage, indications and contraindications of the various drugs that are
      currently available to reduce the risk of further TIA or stroke. Then the
      specific drugs used in the peri-procedural period during carotid stenting will be
      described, along with the evidence supporting their use.

PMID- 16891082
TI  - Classification of acute pancreatitis based on retroperitoneal extension:
      application of the concept of interfascial planes.
AB  - OBJECTIVE: This study aimed to provide a classification system for acute
      pancreatitis by applying the principle that the disease spreads along the
      retroperitoneal interfascial planes. MATERIALS AND METHODS: Medical records and
      computed tomography (CT) images of 58 patients with acute pancreatitis treated
      between 2000 and 2005 were reviewed. The retroperitoneum was subdivided into 10
      components according to the concept of interfascial planes. Severity of acute
      pancreatitis was graded according to retroperitoneal extension into these
      components. Clinical courses and outcomes were compared with the grades. The
      prognostic value of our classification system was compared with that of
      Balthazar's CT severity index (CTSI). RESULTS: Retroperitoneal extension of acute
      fluid collection was classified into five grades: Grade I, fluid confined to the
      anterior pararenal space or retromesenteric plane (8 patients); Grade II, fluid
      spreading into the lateroconal or retrorenal plane (16 patients); Grade III,
      fluid spreading into the combined interfascial plane (8 patients); Grade IV,
      fluid spreading into the subfascial plane beyond the interfascial planes (15
      patients); and Grade V, fluid intruding into the posterior pararenal space (11
      patients). Morbidity and mortality were 92.3% and 38.5% in the 26 patients with
      Grade IV or V disease, and 21.9% and 0% in the 32 patients with Grade I, II, or
      III disease. Morbidity and mortality were 86.7% and 33.3% in patients with
      disease classified "severe" according to the CTSI, and 37.5% and 9.4% in patients
      with disease classified "mild" or "moderate". CONCLUSION: Classification of acute
      pancreatitis based on CT-determined retroperitoneal extension is a useful
      indicator of the disease severity and prognosis without the need for contrast
      medium enhanced CT.

PMID- 16891084
TI  - An overview of recent applications of inductively coupled plasma-mass
      spectrometry (ICP-MS) in determination of inorganic impurities in drugs and
      pharmaceuticals.
AB  - The recent applications of inductively coupled plasma-mass spectrometry (ICP-MS)
      in determination of trace level inorganic impurities in drugs and pharmaceuticals
      have been reviewed. ICP-MS coupled with LC, GC and CE was used for speciation of
      heavy metals in pharmaceutical products. The review covers the period from 1995
      to 2005 during which the technique was applied not only for determination of
      metallic impurities but also the assay of various trace elements in
      pharmaceuticals.

PMID- 16891085
TI  - [Interest of D-lactate as a colic hypoperfusion marker during aortic abdominal
      aneurysm surgery].
AB  - OBJECTIVE: D-lactate is the dextrogyre form of the lactate usually measured in
      intensive care. Its bacterial origin should make it a marker of translocation
      during gut ischemia. The aim was to test D-lactate as a postoperative marker of
      colic hypoperfusion measured during aortic surgery. STUDY DESIGN: Prospective
      observational cohort study. PATIENTS AND MEASUREMENTS: Patients operated for
      abdominal aortic aneurysm. Two groups were stratified on inferior mesenteric
      arterial residual pressure (IMArP) measured during the surgery: Colic
      hypoperfusion during surgery (CHs) group: patients with an IMArP < 40 mmHg.
      CONTROL GROUP: patients with an IMArP > or = 40 mmHg. Baseline data such as age,
      duration of aortic clamping and severity score (IGS II) were collected. The D
      lactate was measured in postoperative at admission time in ICU and then daily. D
      lactate(max) defined the maximum value of D-lactate for one patient. MAIN
      RESULTS: Twenty-nine patients were included, 23 in the control group and 6 in the
      CHs group. Groups were comparable at baseline. D-lactate(max) was significantly
      higher in the CHs group (median: 0.13 mmol/l; min-max: 0.03-0.9 mmol/l) than in
      the control group (0.03; 0-0.26 mmol/l, p=0.007). CONCLUSION: D-lactate could be
      postoperative marker of colic hypoperfusion measured during surgery for abdominal
      aortic aneurysm.

PMID- 16891086
TI  - [Right atrial rupture after abdominal blunt trauma].
AB  - If the cardiac injuries are frequent after closed chest traumatism, the cardiac
      injuries after abdominal closed traumatism are unusual but serious. We report the
      case of a right auricular rupture associated with a liver injury after a closed
      abdominal traumatism. The diagnosis was suspected on the TDM and confirmed by
      echocardiography. An emergency sternotomy was performed due to sudden
      haemodynamic instability. The initial clinical signs are often misleading.
      However the diagnosis must be made quickly and the treatment begun without delay.

PMID- 16891087
TI  - [Relapsing polychondritis: a possible cause of difficult extubation].
AB  - We report the case of a 54-year-old woman suspected of relapsing polychondritis
      who underwent a nasal septum biopsy under general anaesthesia. Tracheal
      intubation was unremarkable, but extubation attempts failed because of upper
      airway inspiratory collapse induced ventilatory distress. Definitive tracheostomy
      placement was mandatory. Cartilage biopsy confirmed severely developed relapsing
      polychondritis. Even though relapsing polychondritis is rare, anaesthesiologists
      should be aware of this pathology and preanaesthetic evaluation may focus on
      particular risks associated with upper airway cartilaginous structure anatomical
      and histological modifications.

PMID- 16891088
TI  - Traumatic extrathoracic lung herniation.

PMID- 16891089
TI  - [Pain management in subarachnoid haemorrhage: a survey of French analgesic
      practices].
AB  - OBJECTIVE: Pain management in patients having a subarachnoid haemorrhage was
      assessed in French intensive care unit of neurosurgical centres. STUDY DESIGN:
      Nationwide survey. METHODS: A standardized postal questionnaire was sent to
      senior doctor of every neurosurgical centres in France inquiring pain scores
      assessment, analgesics used and their routes of administration, centre's opinion
      about efficacy of pain management. RESULTS: Of the 34 centres, 24 returned
      completed questionnaires. Fifty four per cent of the centres evaluated pain
      intensity with a non valid pain score. In the case of patients in the comatose,
      pain was not evaluated in fifty four per cent of the centres. Paracetamol and
      morphine were the most currently used analgesics drugs. Morphine was administered
      subcutaneously by 75% of the centres. Six centres used also PCA. Thirty-seven
      percent of the centres were reluctant to use opioids and 75% to use NSAIDS.
      CONCLUSION: The majority of the centres considered pain management in patient
      suffering from subarachnoid haemorrhage (SAH) was not optimal and stressed the
      need to establish a well validated pain rating scale dedicated to SAH patients.

PMID- 16891090
TI  - [Atlantoaxial subluxation with spastic torticollis after cardiorespiratory
      resuscitation].

PMID- 16891091
TI  - [When the anaesthesist's vein turns into artery!].

PMID- 16891092
TI  - [Pulmonary oedema after a knee arthroscopy].
AB  - Negative pressure pulmonary oedema is one form of non cardiogenic pulmonary
      oedema that can occur following any general anaesthesia in which the patient was
      intubated. This complication can be severe, resulting in death/life-threatening
      if not diagnosed and treated promptly. We report a case of negative pressure
      pulmonary oedema, in a 26-year-old man, secondary to inspiratory effort with
      laryngeal spasm. Patient was transferred to intensive care unit for monitoring
      and non invasive ventilation. Prevention, early diagnosis, and prompt treatment
      allowed a rapid and uncomplicated resolution.

PMID- 16891093
TI  - Role of 18F-FDG-PET and PET/CT imaging in thyroid cancer.
AB  - In patients affected by differentiated thyroid cancer (DTC), the lacking of
      131Iodine trapping by metastatic tissue does not allow 131Iodine whole body
      scintigraphy to visualize matastatic spread as well as the use of 131Iodine
      therapy to cure such metastatic spread. Prognosis of 131Iodine-negative DTC
      metastasis, so-called non-functioning metastasis, is significantly worst. In
      these patients an early diagnosis of non-functioning metastasis and their
      surgical extirpation remains the optimal therapeutic approach. In this view, a
      high sensitive localizing imaging different form 131Iodine whole body
      scintigraphy is required. Ultrasonography is characterized by a relatively high
      sensitivity in these patients but it is highly operator-dependent and, moreover,
      it can be used to explore neck alone. Computed tomography (CT) scan and magnetic
      resonance (MR) imaging are characterized by a relatively low sensitivity even if
      they are useful to provide the surgeon with anatomical information of the
      operating basin. Various tumor-seeking radiotracers have been proposed, mainly
      using SPECT as 201Thallium, 99mTc-Sestamibi and 99mTc-Tetrofosmin with good
      results. Even more favorable results have been reported with some positron
      radiotracers, mainly the 18F-FDG with PET and more recently with PET/CT
      tomographs. The typical indication to performing with examination is the DTC
      patient previously treated by total thyroidectomy and 131Iodine ablative therapy,
      with increased serum thyroglobulin (Tg) or anti-thyroglobulin (TgAb) antibodies
      during follow-up but with negative 131Iodine whole body scintigraphy even
      obtained after high, therapeutic 131Iodine doses. Several studies in literature
      have reported high sensitivity (up to 85%) and specificity (up to 95%) of FDG-PET
      in metastatic DTC patients. The integrated PET/CT fusion imaging systems, seem
      able to provide some additional advantages over PET alone, mainly related to a
      better anatomical localization of the hypermetabolic metastatic lesions. A change
      in the management of DTC patients affected by non-functioning metastatic spread
      not visualized by other imaging techniques has been reported in 30% of patients.
      Lastly, the role of PET and PET/CT fusion imaging systems seem to be promising
      also in patients affected by medullary thyroid carcinoma (MTC), especially for
      the detection of neck and mediastinal lesions, with a sensitivity superior to the
      other currently available imaging methods, however the data reported on medullary
      cancer are little and further studies are needed to elucidate the preliminary
      promising results.

PMID- 16891094
TI  - Functional evaluation of the autoimmunity-associated CTLA4 gene: the effect of
      the (AT) repeat in the 3'untranslated region (UTR).
AB  - The third confirmed susceptibility locus in type 1 diabetes (T1D), the CTLA4
      gene, harbors several DNA variants in linkage disequilibrium (LD), any one of
      which, or a combination thereof, could contribute to an individual's
      susceptibility to disease. Dissecting their contribution to disease requires both
      genetic and functional studies at each locus, due to the quasi 100% LD in the
      region. To this effect we have undertaken a detailed functional analysis of the
      (AT)(n) dinucleotide repeat located in the 3'untranslated region (UTR) using
      validated methodology for detecting allelic differences in expression in
      individuals heterozygous for the most common alleles at the 3'UTR (AT)(n) repeat,
      the 88bp and 106bp alleles, which combined account for two thirds of all
      chromosomes. We hypothesized that such a dinucleotide repeat may alter the
      stability of the messenger RNA, and assessed the stability of each allelic
      derived messenger RNA in heterozygous individuals by treating steady-state mRNA
      with the transcription attenuator, actinomycin D. We report no difference between
      mRNAs carrying an 88bp repeat allele or 106bp, and no effects of the repeat
      expansion on the stability of the mRNA.

PMID- 16891096
TI  - Quantitative morphometric analysis of hair follicles in alopecia areata.

PMID- 16891095
TI  - Association of eNOS gene polymorphism (Glu298Asp) with psoriasis.

PMID- 16891097
TI  - Use of ceftriaxone in patients with severe leptospirosis.
AB  - The optimal treatment of severe and late leptospirosis, and even the need for
      antibiotic treatment in such clinical settings, remains a subject of debate.
      Twenty-two patients with severe late leptospirosis were treated with intravenous
      ceftriaxone 2g daily. Twenty-one patients recovered and one patient passed away
      due to respiratory complications of the disease. The adverse effect profile and
      the convenience of the regimen were superior to penicillin regimens reported in
      other clinical trials. Ceftriaxone may be a reasonable alternative in severe
      leptospirosis as an efficient, convenient and safe regimen. Large multicentre
      studies may further define the optimal interventions in severe leptospirosis as
      well as possible variations in the pathogenic and clinical parameters of
      respiratory leptospirosis.

PMID- 16891098
TI  - Treatment of experimental chronic pulmonary mycoplasmosis.
AB  - Mycoplasma pneumoniae infection has been associated with chronic lung disease.
      Treatment of chronic pulmonary mycoplasmosis has not been well investigated.
      BALB/c mice were intranasally inoculated once with M. pneumoniae or with sterile
      media (uninfected controls). Infected mice were treated with telithromycin or
      placebo daily for 10 days in the chronic phase of disease (18 months after
      inoculation). Mice (n=43) were evaluated before therapy and 1 day after
      completion of telithromycin. Treatment of infected mice with telithromycin at 18
      months after infection significantly reduced chronic pulmonary histological
      inflammation compared with infected mice given placebo; however, this treatment
      did not improve airway obstruction or airway hyperresponsiveness. Therapy longer
      than 10 days may be necessary to improve pulmonary function.

PMID- 16891099
TI  - Evidence for a protective role for adiponectin in osteoarthritis.
AB  - Obesity has been associated with an increased risk of osteoarthritis (OA).
      However, the mechanism by which obesity contributes to OA remains uncertain.
      Adiponectin, an adipocyte-derived hormone, has shown anti-diabetic and anti
      atherogenic properties. In the present study, we aimed to investigate the
      potential role of adiponectin in OA disease. We demonstrated that adiponectin was
      present in OA synovial fluid (SF) and its expression level was almost 100-fold
      decrease compared with that in OA plasma. FPLC and ELISA studies revealed the
      distribution and abundance of the adiponectin complexes in plasma and SF from
      patients with OA. The percentage of high molecular weight (HMW) per total
      adiponectin in OA SF was lower than in OA plasma, while that of the hexamer form
      was similar and the trimer form was higher. The expression levels of adiponectin
      receptors AdipoR1 and AdipoR2 were examined in human OA tissues by RT-PCR.
      AdipoR1 was abundantly expressed in cartilage, bone and synovial tissues, whereas
      AdipoR2 was rarely detected. Finally, the effects of adiponectin on primary
      chondrocyte functions were studied by using antibody-based protein array and RT
      PCR. The patterns of mRNA expression and protein production strongly indicate
      that adiponectin is involved in the modulation of cartilage destruction in
      chondrocytes by up-regulating TIMP-2 and down-regulating IL-1beta-induced MMP-13.
      Together these findings clearly indicate that the adiponectin may act as a
      protective role in the progression of OA, and this also provide new thinking on
      the relationship between obesity and OA.

PMID- 16891100
TI  - In vitro tau fibrillization: mapping protein regions.
AB  - We have investigated the propensity to form fibrillar aggregates of a variety of
      fragments and variants of the tau protein under the influence of a tau
      fibrillization inducer: coenzyme Q(0). To better identify fibrillization
      hotspots, we compare the polymerization propensity of tau fragments containing
      the sequence of putative hotspots with that of tau variants with that same
      sequence deleted. We also investigate the effects of biologically occurring
      modifications such as phosphorylation and deamidation. We found that residues 305
      to 335 are essential for in vitro tau fibrillization. Residues 306 to 311
      facilitate in vitro assembly, but are not sufficient to mimic the in vivo
      fibrillization of tau. Furthermore, the propensity of the 306-311 sequence to
      form fibrils is highly decreased by chemical modifications of tyrosine 310 that
      are commonly found in vivo.

PMID- 16891101
TI  - [A diplopia with fever].

PMID- 16891102
TI  - Primary role of superoxide anion generation in the cascade of events leading to
      endothelial dysfunction and damage in high glucose treated HUVEC.
AB  - AIM: The aim of the study was to elucidate the chain of events leading to
      oxidative damage in endothelial cells exposed to high glucose. METHOD: The nitric
      oxide synthase (NOS) cofactor tetrahydrobiopterin (BH4), the peroxynitrite
      decomposition catalyst FP15, the inhibitor of mitochondrial complex II
      thenoyltrifluoroacetone (TTFA) and the antioxidant superoxide dismutase (SOD)
      mimetic Mn(III)tetrakis(4-benzoic acid) porphyrin chloride (MnTBAP) were
      individually added to human umbilical vein endothelial cells (HUVEC) cultured in
      high glucose. This study was designed to establish the possible sequence of
      action of NOS, peroxynitrite and superoxide anion in the oxidative damage
      cascade. RESULTS: We found that in high glucose, nitrotyrosine, 8OHdG, NO (+40%)
      and O2- (+300%) production, eNOS and caspase-3 expression increased, while Bcl-2
      expression decreased. MnTBAP and TTFA were able to normalize all the parameters
      assayed. FP15 caused an increase in NO production, did not interfere with eNOS
      expression and O2- generation, but was able to reduce apoptosis and to normalize
      nitrotyrosine and 8OHdG formation. BH4 enrichment was able to reduce O2-
      generation, nitrotyrosine and 8OHdG formation and apoptosis. The addition of this
      cofactor did not affect eNOS expression, but increased NO formation, more than
      FP15. CONCLUSION: These data show the starting role of superoxide anion generated
      at mitochondrial level in the cascade of events leading to hyperglycemia
      generated apoptosis.

PMID- 16891103
TI  - A type-1 metacaspase from Acanthamoeba castellanii.
AB  - The complete sequence of a type-1 metacaspase from Acanthamoeba castellanii is
      reported comprising 478 amino acids. The metacaspase was recovered from an
      expression library using sera specific for membrane components implicated in
      stimulating encystation. A central domain of 155 amino acid residues contains the
      Cys/His catalytic dyad and is the most conserved region containing at least 30
      amino acid identities in all metacaspases. The Acanthamoeba castellanii
      metacaspase has the most proline-rich N-terminus so far reported in type-1
      metacaspases with over 40 prolines in the first 150 residues. Ala-Pro-Pro is
      present 11 times. Phylogenies constructed using only the conserved proteolytic
      domains or the complete sequences show identical branching patterns, differing
      only in the rates of change.

PMID- 16891104
TI  - Reorganization of mycelial networks of Phanerochaete velutina in response to new
      woody resources and collembola (Folsomia candida) grazing.
AB  - Mycelial development of Phanerochaete velutina extending from wood inocula in 57
      x 57 cm trays of non-sterile soil was characterized after adding: (1) collembola;
      (2) new wood resources; (3) both new wood resources and collembola; and (4) no
      new resources and no collembola. After 99 d, all systems had produced distinct
      mycelial cords, much of the diffuse mycelium and thinner cords that were produced
      early on having regressed. Systems to which new resources (but no collembola) had
      been added developed thick cords interconnecting inocula with new resources, and
      much of the non-connected mycelium regressed. Nonetheless, these systems had
      significantly greater hyphal coverage and mass fractal dimension than the other
      treatments, resulting from outgrowth from the new resources. Unexpectedly,
      morphology of grazed systems with no added resources was very similar to that of
      ungrazed systems with no added resources, apparently because the collembola
      grazed on senescing hyphae that would ultimately have regressed. Where new
      resources and collembola were added, there was proliferation of fine mycelium
      along connective cords and elsewhere, but this was not as extensive as in the new
      resource/no collembola systems, the fine mycelium apparently being grazed in
      patches. Fungus gnat (family Sciaridae) larvae contaminated eight (out of 14)
      trays with no added collembola, but none of the systems to which collembola had
      been added. They burrowed around the wood and caused cords to be severed.

PMID- 16891105
TI  - Fungal surface remodelling visualized by atomic force microscopy.
AB  - Most fungal growth is localized to the tips of hyphae, however, early stages of
      spore germination and the growth of certain morphological mutant strains exhibit
      non-polarized expansion. We used atomic force microscopy (AFM) to document
      changes in Aspergillus nidulans wall surfaces during non-polarized growth: spore
      germination, and growth in a strain containing the hypA1 temperature sensitive
      morphogenesis defect. We compared wall surface structures of both wild-type and
      mutant A. nidulans following growth at 28 degrees and 42 degrees C, the latter
      being the restrictive temperature for hypA1. There was no appreciable difference
      in surface ultrastructure between wild-type and hypA1 spores, or hyphal walls
      grown at 28 degrees C. When dry mature A. nidulans conidia were wetted they lost
      their hydrophobin coat, indicating an intermediate stage between dormancy and
      swelling. The surface structure of hypA1 germlings grown at 42 degrees C was less
      organized than wild-type hyphae grown under the same conditions, and had a larger
      range of subunit sizes. AFM images of hyphal wall surface changes following a
      shift in growth temperature from restrictive (42 degrees C) to permissive (28
      degrees C), showed a gradient of sizes for wall surface features similar to the
      trend observed for wild-type cells at branch points. Changes associated with the
      hyphal wall structure for A. nidulans hypA1 offer insight into the events
      associated with fungal germination, and wall remodelling.

PMID- 16891106
TI  - Identification and characterization of non-pathogenic Fusarium oxysporum capable
      of increasing and decreasing Fusarium wilt severity.
AB  - Fusarium wilt of banana is a potentially devastating disease throughout the
      world. Options for control of the causal organism, Fusarium oxysporum f.sp.
      cubense (Foc) are limited. Suppressive soil sites have previously been identified
      where, despite the presence of Foc, Fusarium wilt does not develop. In order to
      understand some aspects of this disease suppression, endophytic Fusarium
      oxysporum isolates were obtained from banana roots. These isolates were
      genetically characterized and compared with an isolate of Fusarium oxysporum
      previously identified as being capable of suppressing Fusarium wilt of banana in
      glasshouse trials. Three additional isolates were selected for glasshouse trials
      to assess suppression of Fusarium wilt in two different cultivars of banana,
      Cavendish and Lady Finger. One isolate (BRIP 29089) was identified as a potential
      biocontrol organism, reducing the disease severity of Fusarium wilt in Lady
      Finger and Cavendish cultivars. Interestingly, one isolate (BRIP 45952) increased
      Fusarium wilt disease severity on Cavendish. The implications of an isolate of
      Fusarium oxysporum, non-pathogenic on banana, increasing disease severity and the
      potential role of non-pathogenic isolates of Fusarium oxysporum in disease
      complexes are discussed.

PMID- 16891107
TI  - Influence of the region of origin on the mycobiota of grapes with emphasis on
      Aspergillus and Penicillium species.
AB  - A three-year study was undertaken to investigate the fungal species present on
      the surface of grape berries from Portuguese vineyards in four winemaking
      regions. Emphasis was given to Aspergillus and Penicillium species due to their
      relevance for mycotoxin production. From the 3517 fungal strains detected 27
      genera were identified. The region of origin markedly influenced the spoilage
      fungal population to which berries are exposed. The main differences found were
      in the incidence of A. niger aggregate, Botryis cinerea and Penicillium species
      (P. brevicompactum, P. citrinum, P. glabrum/spinulosum, P. expansum, P.
      implicatum and P. thomii). In more humid climates, Botrytis seems to be the main
      pathogen and spoiling agent, and the incidence of black Aspergillus is minimal.
      The most important mycotoxin-producing species found was A. carbonarius, which is
      an ochratoxin A producer. The present study provides a detailed description of
      the fungi found on the berry surface of Portuguese grapes and shows the
      Aspergillus and Penicillium species, which vary significantly by geographic
      origin. This is of crucial importance to understand fungal hazards for grapes and
      wine and to the knowledge of field ecology of the species.

PMID- 16891108
TI  - Association of depression and anxiety with health care use and quality of life in
      asthma patients.
AB  - INTRODUCTION: Demographic factors, symptom severity, and psychopathology, in
      particular anxiety and depression, are known to influence health care use and
      quality of life in asthma. Because depression and anxiety are typically
      correlated, we sought to explore whether depression specifically is associated
      with health care utilization and quality of life when effects of anxiety are
      controlled for. METHOD: In a cross-sectional questionnaire study, 88 asthma
      patients (46 women; age range 27-70 years) reported on symptoms and treatment of
      their disease, as well as anxiety and depression (Hospital Anxiety and Depression
      Scale, HADS), general quality of life (Short Form 12 Health Survey Questionnaire,
      SF-12) and asthmatic-specific quality of life (Living with Asthma, LAQ). RESULTS:
      While no considerable associations between anxiety and health care use were
      found, the associations between higher scores in depression and hospital visits
      as well as days of corticosteroid intake were significant. Furthermore,
      considerable variance in all subscales of quality of life questionnaires was
      explained by higher scores in depression, even when controlling for anxiety. For
      anxiety scores these associations were comparable, except for physical well
      being. CONCLUSION: Depression is an important issue in asthma, as it is
      substantially related to quality of life and intake of corticosteroids, and
      marginally to hospitalization. Routine screening for depression should be
      considered in hospital and primary care.

PMID- 16891109
TI  - CombiMatrix oligonucleotide arrays: genotyping and gene expression assays
      employing electrochemical detection.
AB  - Electrochemical detection has been developed and assay performances studied for
      the CombiMatrix oligonucleotide microarray platform that contains 12,544
      individually addressable microelectrodes (features) in a semiconductor matrix.
      The approach is based on the detection of redox active chemistries (such as
      horseradish peroxidase (HRP) and the associated substrate TMB) proximal to
      specific microarray electrodes. First, microarray probes are hybridized to biotin
      labeled targets, second, the HRP-streptavidin conjugate binds to biotin, and
      enzymatic oxidation of the electron donor substrate then occurs. The detection
      current is generated due to electro-reduction of the HRP reaction product, and it
      is measured with the CombiMatrix ElectraSense Reader. Performance of the
      ElectraSense platform has been characterized using gene expression and genotyping
      assays to analyze: (i) signal to concentration dependence, (ii) assay resolution,
      (iii) coefficients of variation, (CV) and (iv) array-to-array reproducibility and
      data correlation. The ElectraSense platform was also compared to the standard
      fluorescent detection, and good consistency was observed between these two
      different detection techniques. A lower detection limit of 0.75 pM was obtained
      for ElectraSense as compared to the detection limit of 1.5 pM obtained for
      fluorescent detection. Thus, the ElectraSense platform has been used to develop
      nucleic acid assays for highly accurate genotyping of a variety of pathogens
      including bio-threat agents (such as Bacillus anthracis, Yersinia pestis, and
      other microorganisms including Escherichia coli, Bacillus subtilis, etc.) and
      common pathogens of the respiratory tract (e.g. influenza A virus).

PMID- 16891110
TI  - Molecularly imprinted polymers for the recognition of proteins: the state of the
      art.
AB  - Molecular imprinting has proved to be an effective technique for the creation of
      recognition sites on a polymer scaffold. Protein imprinting has been a focus for
      many chemists working in the area of molecular recognition, since the creation of
      synthetic polymers that can specifically recognise proteins is a very challenging
      but potentially extremely rewarding objective. It is expected that molecularly
      imprinted polymers (MIPs) with specificity for proteins will find application in
      medicine, diagnostics, proteomics, environmental analysis, sensors and drug
      delivery. In this review, the authors provide an overview of the progress
      achieved in the decade between 1994 and 2005, with respect to the challenging
      area of MIPs for protein recognition. The discussion furnishes a comparative
      analysis of different approaches developed, underlining their relative advantages
      and disadvantages and highlighting trends and possible future directions.

PMID- 16891111
TI  - Incidence of and survival from Wilms' tumour in adults in Europe: data from the
      EUROCARE study.
AB  - Wilms' tumour, or nephroblastoma, is an embryonal cancer of the kidney that
      occurs mainly in young children. This is a very rare tumour among adults, with an
      incidence rate of less than 0.2 per million per year. The aims of this study were
      to report the survival of adults diagnosed with nephroblastoma in Europe and to
      analyse time trends and geographic variations in survival. All the adults (age
      range 15-99 years) diagnosed with a Wilms' tumour during 1983-1994 and registered
      by one of the 22 cancer registries in 16 countries contributing to the EUROCARE
      (European cancer registries study on cancer patients' survival and care) database
      were analysed. Relative survival at 1 and 5 years after diagnosis was estimated
      by age, sex, geographic area, period of diagnosis and tumour stage. A total of
      143 patients, with a median age of 34 years, were included in the analysis. Crude
      annual incidence rates varied geographically between 0.17 and 0.27 per million.
      Overall relative survival was 69.9% (95% confidence interval (CI) 61.8-78.0%) at
      1 year and 47.3% (38.2-56.4%) at 5 years. Survival was 2.1-fold higher for women
      than for men (95% CI 1.3-3.5). There was a non-significant trend for better
      survival for younger patients and localised tumours, but no improvement in
      survival by period of diagnosis. Survival was not different between geographic
      areas. Our results suggest a poorer outcome of nephroblastoma in adults compared
      with published results in children. This may, at least partly, be explained by
      the rarity of this diagnosis. Prognosis may be improved by the use of specific
      treatment guidelines for nephroblastoma in adults.

PMID- 16891112
TI  - Phase 1 European Organisation for Research and Treatment of Cancer study
      determining safety of pegylated liposomal doxorubicin (Caelyx) in combination
      with ifosfamide in previously untreated adult patients with advanced or
      metastatic soft tissue sarcomas.
AB  - This phase I study evaluated the toxicity of first-line combined pegylated
      liposomal doxorubicin (Caelyx) and ifosfamide in patients with advanced and/or
      metastatic soft tissue sarcomas. Five dose levels (L) were studied: Caelyx 30
      mg/m2 (L1-4) or 40 mg/m2 (L5) 1-h infusion d 1 q 3 weeks + ifosfamide and mesna
      at X g/m2/4 h d 1-3 q 3 weeks at five doses: L1: X = 1.7 g; L2: X = 2 g; L3: X =
      2.5 g; L4 and L5: X = 3 g. Cohorts of 3 patients were entered at each level
      unless a dose-limiting toxicity (DLT) occurred. In case of DLT in 1 of 3 patients
      a new cohort was added. Toxicity was evaluated by Common Toxicity Criteria (CTC).
      A total of 28 patients was included: 4 at dose L1, 8 at L2, 3 at L3, 6 at L4, and
      7 at L5. Median age was 60 years (range 29-69 years). Male/female ratio was
      12/16. Seventy-five percent of patients had a performance status of 1.0 and 36%
      had leiomyosarcomas. No DLT was observed at dose L1-4. Six patients developed a
      DLT at dose L5, and thus the recommended dose is level 4 (i.e. Caelyx 30 mg/m2/1
      h d 1+ifosfamide at 3 g/m2/4 h d 1-3 q 3 weeks). Few haematological and
      biochemical events were observed and the principal toxicities were
      granulocytopaenia and leucopaenia. Five patients discontinued therapy because of
      toxicity, 4 of them at dose level 5. Non-haematological toxicities > grade 2 were
      also few. Palmar-plantar erythrodysesthesia (PPE) > grade 1 was not seen. Two
      patients obtained partial response (PR) and 13 stable disease (SD). Median
      overall survival (OS) was 333 d and median progression-free survival (PFS) 174 d.
      In conclusion, this seems to be a feasible combination in patients with advanced
      soft tissue sarcomas, allowing ifosfamide to be given in a dosage similar to that
      used when given alone. The recommended dose for future studies is Caelyx 30
      mg/m2/1 h d 1+ifosfamide 3 g/m2/4 h d 1-3 q 3 weeks.

PMID- 16891113
TI  - ORF18-disrupted mutant of Comamonas testosteroni TA441 accumulates significant
      amounts of 9,17-dioxo-1,2,3,4,10,19-hexanorandrostan-5-oic acid and its
      derivatives after incubation with steroids.
AB  - In a steroid degradation gene cluster of Comamonas testosteroni TA441 consisting
      of ORF18, 17 and tesIHA2A1DEFG, ORF18 was implicated in encoding a CoA
      transferase by database searches, but the matching substrate was not clear. In
      this study, ORF18 was shown to be necessary for conversion of 9,17-dioxo
      1,2,3,4,10,19-hexanorandrostan-5-oic acid, a product of hydrolysis of 4,5-9,10
      diseco-3-hydroxy-5,9,17-trioxoandrosta-1(10),2-dien-4-oic acid in steroid
      degradation by TA441. The ORF18-disrupted mutant accumulates 7-hydroxy-9,17-dioxo
      1,2,3,4,10,19-hexanorandrostan-5-oic acid and 7,12-dihydroxy-9,17-dioxo
      1,2,3,4,10,19-hexanorandrostan-5-oic acid when incubated with chenodeoxycholic
      acid and cholic acid, respectively.

PMID- 16891114
TI  - Functional genomics approaches for the study of sporadic adrenal tumor
      pathogenesis: clinical implications.
AB  - Although sporadic adrenal tumors are frequently encountered in the general
      population their pathogenesis is not well elucidated. The advent of functional
      genomics/bioinformatics tools enabling large scale comprehensive genome
      expression profiling should contribute to significant progress in this field.
      Some studies have already been published describing gene expression profiles of
      benign and malignant adrenocortical tumors and phaeochromocytomas. Several genes
      coding for growth factors and their receptors, enzymes involved in steroid
      hormone biosynthesis, genes related to the regulation of cell cycle, cell
      proliferation, adhesion and intracellular metabolism have been found to be up- or
      downregulated in various tumors. Some alterations in gene expression appear so
      specific for certain tumor types that their application in diagnosis,
      determination of prognosis and the choice of therapy can be envisaged. In this
      short review, the authors will present a synopsis of these recent findings that
      seem to open new perspectives in adrenal tumor pathogenesis, with emphasis on
      changes in steroidogenic enzyme expression profiles and highlighting possible
      clinical implications.

PMID- 16891115
TI  - Actions of gonadotropin-releasing hormone analogues in pituitary gonadotrophs and
      their modulation by ovarian steroids.
AB  - Recently, GnRH antagonists (GnRHant) like cetrorelix and ganirelix have been
      introduced in protocols of controlled ovarian hyperstimulation for assisted
      reproductive techniques to prevent premature luteinizing hormone (LH) surges.
      Here we tested, whether the actions of cetrorelix and the GnRH agonist (GnRHag)
      triptorelin in gonadotrophs are dependent on the steroid milieu. Furthermore, we
      characterized the actions of cetrorelix and triptorelin on LH secretion and the
      total LH pool. Female rat pituitary cells were treated either with 0.1 nM
      triptorelin for 1, 2, 4 and 6 days or for 1, 3, 5 and 6 h or with 1, 10 or 100 nM
      cetrorelix for 1, 2, 3 and 5 h or for 10 min. Cells were stimulated for 3h with
      different concentrations of GnRH (10 pM-1 microM). For analysis of the total LH
      pool, which is composed of stored and released LH, cells were lysed with 0.1%
      Triton X-100 at -80 degrees C overnight. To test, whether the steroid milieu
      affects the actions of cetrorelix and triptorelin, cells were incubated for 52 h
      with 1 nM estradiol (E) alone or with combinations of 100 nM progesterone (P) for
      4 or 52 h, respectively. Cells were then treated with 0.1 nM triptorelin for 9 h
      or 1 nM cetrorelix for 3 h and stimulated for 3 h with different concentrations
      of GnRH (10 pM-1 microM). The suppressive effect of triptorelin on LH secretion
      was fully accomplished after 3 h of treatment, for cetrorelix only 10 min were
      sufficient. The concentration of cetrorelix must be at least equimolar to GnRH to
      block LH secretion. Cetrorelix shifted the EC50s of the GnRH dose-response curve
      to the right. Triptorelin suppressed total LH significantly (from 137 to 36
      ng/ml) after 1 h in a time-dependent manner. In contrast, only high
      concentrations of cetrorelix increased total LH. In steroid treated cells the
      suppressive effects of triptorelin were more distinct. One nanomolar cetrorelix
      suppressed GnRH-stimulated LH secretion of cells not treated with steroids from
      10.1 to 3.5 ng/ml. In cells, additionally treated with estradiol alone or
      estradiol and short-term progesterone, LH levels were higher (from 3.5 to 5.4 or
      4.5 ng/ml, respectively). In cells co-treated with estradiol and progesterone for
      52 h LH secretion was only suppressed from 10.1 to 9.5 ng/ml. Steroid treatments
      diminished the suppressive effect of cetrorelix on LH secretion. In conclusion,
      the depletion of the total LH pool contributes to the desensitizing effect of
      triptorelin. The actions of cetrorelix and triptorelin are dependent on the
      steroid milieu.

PMID- 16891116
TI  - Colorectal cancer follow-up: useful or useless?
AB  - Follow-up of surgically treated colorectal cancer patients is not supported by
      objectively certain data. Despite the thousands of investigations reported in the
      scientific literature, only six randomized prospective studies and two meta
      analysis of randomized studies provide data suggesting clear conclusions. Our
      review of the literature revealed that intensive colorectal follow-up should be
      performed even if the long-term survival benefit is small. The timing and
      investigations conducted in follow-ups diverge. The inconsistency of follow-ups
      is revealed by the fact that the leading USA and European societies propose
      different guidelines. One datum that the literature agrees on is that
      pancolonoscopy performed at 3-5 year intervals in colorectal cancer surgery
      patients supports diagnosis of adenomatous polyps and metachronous cancers. Cost
      analysis have shown that intensive follow-up would certainly exceed the cut-off
      point level set for every additional year of good quality of life.

PMID- 16891118
TI  - Synthesis and evaluation of alpha-hydroxymethylated conjugated nitroalkenes for
      their anticancer activity: inhibition of cell proliferation by targeting
      microtubules.
AB  - The Morita-Baylis-Hillman (MBH) type reaction of a variety of aromatic and
      heteroaromatic conjugated nitroalkenes with formaldehyde in the presence of
      stoichiometric amounts of imidazole and catalytic amounts (10 mol %) of
      anthranilic acid at room temperature provided the corresponding hydroxymethylated
      derivatives in moderate to good yield. The parent nitroalkenes and their MBH
      adducts were subsequently screened for their anticancer activity. Some of the MBH
      adducts were found to inhibit cervical cancer (HeLa) cell proliferation at low
      micromolar concentrations with half-maximal inhibitory concentrations in the
      range of 1-2 microM. The antiproliferative activity of 3-((E)-2-nitrovinyl)furan
      and three potent MBH adducts, namely, hydroxymethylated derivatives of 3-((E)-2
      nitrovinyl)thiophene, 1-methoxy-4-((E)-2-nitrovinyl)benzene, and 1,2-dimethoxy-4
      ((E)-2-nitrovinyl)benzene was correlated well with their antimicrotubule
      activity. At their effective concentration range, the tested compounds perturbed
      the organization of mitotic spindle microtubules and chromosomes. In the presence
      of hydroxymethylated nitroalkenes, abnormal bipolar or multipolar mitotic
      spindles were apparent. Interphase microtubules were found to be significantly
      depolymerized at relatively higher concentrations of the tested compounds. These
      compounds inhibited tubulin assembly into microtubules in vitro by binding to
      tubulin at a site distinct from the vinblastine and colchicine binding sites. The
      compounds reduced the intrinsic tryptophan fluorescence of tubulin and the
      fluorescence of tubulin-1-anilinonaphthalene-8-sulfonic acid (ANS) complex
      indicating that they induced conformational changes in the tubulin. The results
      suggest that hydroxymethylated nitroalkenes exert their antiproliferative
      activity at least in part by depolymerizing cellular microtubules through tubulin
      binding and indicate that hydroxymethylated nitroalkenes are promising lead
      compounds for cancer therapy.

PMID- 16891117
TI  - Synthesis, radiolabeling, and in vivo evaluation of an 18F-labeled isatin analog
      for imaging caspase-3 activation in apoptosis.
AB  - A non-peptide-based isatin sulfonamide analog, WC-II-89, was synthesized and its
      inhibition toward recombinant human caspase-3 and other caspases was determined.
      This compound showed high potency for inhibiting caspase-3 and -7, and high
      selectivity against caspases-1, -6, and -8. [(18)F]WC-II-89 was synthesized via a
      nucleophilic substitution of the corresponding mesylate precursor in high yield
      and radiochemical purity. Biodistribution studies using [(18)F]WC-II-89 revealed
      higher uptake in liver and spleen of cycloheximide-treated rats, an animal model
      of apoptosis, relative to control animals. Western blot analysis confirmed the
      presence of activated caspase-3 in the liver and spleen of cycloheximide-treated
      animals. MicroPET imaging studies revealed a high uptake of the radiotracer in
      the liver of a cycloheximide-treated rat relative to the untreated control. These
      data suggest that [(18)F]WC-II-89 is a potential radiotracer for imaging caspase
      3 activation in tissues undergoing apoptosis.

PMID- 16891119
TI  - Flavonoids and cinnamic acid esters as inhibitors of fungal 17beta-hydroxysteroid
      dehydrogenase: a synthesis, QSAR and modelling study.
AB  - The 17beta-hydroxysteroid dehydrogenases (17beta-HSDs) modulate the biological
      potency of estrogens and androgens by interconversion of inactive 17-keto
      steroids and their active 17beta-hydroxy- counterparts. We have shown previously
      that flavonoids are potentially useful lead compounds for developing inhibitors
      of 17beta-HSDs. In this paper, we describe the synthesis and biochemical
      evaluation of structurally analogous inhibitors, the trans-cinnamic acid esters
      and related compounds. Additionally, quantitative structure-activity relationship
      (QSAR) and modelling studies were performed to rationalize the results and to
      suggest further optimization. The results stress the importance of a hydrogen
      bond with Asn154 and hydrophobic interactions with the aromatic side chain of
      Tyr212 for optimal molecular recognition.

PMID- 16891120
TI  - Recent progress of nano-technology with NSOM.
AB  - Recent progress of nano-technology with near-field scanning optical microscope
      (NSOM) is surveyed in this article. We focus mainly on NSOM, nano-scale
      spectroscopy with NSOM, probe technology of NSOM, and study of nano-structured
      metallic surface with NSOM. First, we follow developments of aperture NSOM and
      apertureless NSOM, and then address progress of NSOM-combined spectroscopy which
      is so sufficiently advanced with apertureless NSOM technology to provide chemical
      information on length scales of a few nanometers. Recent achievement of nano
      scale Raman and IR spectroscopy will be introduced. Finally, research on nano
      optic elements using surface plasmon polariton with NSOM is introduced as an
      example of NSOM applications to nano-structured metallic surfaces.

PMID- 16891121
TI  - Preparation and activity measurement of electrodeposited alpha-emitting sources.
AB  - Alpha-emitting 238Pu and 241Am sources on stainless steel substrates have been
      prepared using a new electrodeposition method based on an ammonium oxalate
      ammonium sulfate electrolyte containing diethyl triamino pentaacetic acid. The
      deposition yield is determined by measuring the activity of the sources using a
      high-efficiency 2pi alpha proportional counter and a backscattering chamber
      designed and fabricated for this purpose. Optimal electrodeposition parameters
      have been determined for 241Am, enabling manufacture of standard alpha-emitting
      sources with minimal radioactive waste.

PMID- 16891122
TI  - Ultrastructural examination of the host inflammatory response within gills of
      netpen reared chinook salmon (Oncorhynchus tshawytscha) with Microsporidial Gill
      Disease.
AB  - The sequence of host changes following the rupture of spore-laden xenomas of the
      microsporidian Loma salmonae during Microsporidial Gill Disease of Salmon was
      deduced from ultrastructural examination of the gills of naturally infected,
      moribund, chinook salmon from a commercial aquaculture site. The gills contained
      many stages of parasite development suggesting fish were chronically exposed to
      the parasite. Intact xenomas were generally found beneath the endothelium in
      arteries and arterioles and were encapsulated by a layer of collagen containing
      fibroblasts sometimes joined by desmosomes. Xenoma dissolution was characterized
      by neutrophil infiltration and loss of the xenoma plasma membrane and
      encapsulation. The inflammatory responses associated with ruptured xenomas ranged
      from acute lesions, denoted by a marked neutrophil infiltration and vascular
      thrombosis, to chronic lesions with a macrophage-rich infiltrate variously
      accompanied by neovascularization and vascular remodelling. Dendritic-like cells
      and plasma cells were characteristic throughout. Basement membrane damage of the
      primary filament epithelium and subsequent transepithelial expulsion of spores
      were associated with severe inflammation. An unusual previously undescribed
      multifocal change, in which epithelial cells invaded deeply beyond the normal
      boundaries of the basement membrane, affected areas of gill filament epithelium
      with basement membrane damage. Some neutrophils that contained L. salmonae
      spores, or spore polar tube, displayed morphological changes that included
      irregular cell shape, cytoplasmic darkening associated with an abundance of free
      ribosomes, lysis of neighbouring cells, and type II nuclear clefts. Fusion of
      apparently intact neutrophils occurred in other areas of the lesion, where close
      contacts between neighbouring cells were established and in some areas plasma
      membrane fusion occurred. Closely associated neutrophils with intact plasma
      membranes were observed to contain type II nuclear clefts, abundant granules and
      rough endoplasmic reticulum. Other neutrophils in the lesion displayed type I
      nuclear pockets, which is suspected to be an early stage of apoptosis.

PMID- 16891123
TI  - Transcranial magnetic stimulation during resistance training of the tibialis
      anterior muscle.
AB  - During the first few weeks of resistance training, maximal voluntary contraction
      (MVC) force increases at a faster rate than can be accounted for by increases in
      protein synthesis. This early increase in MVC force has been attributed to neural
      mechanisms but the sources have not been identified. The purpose of this study
      was to measure changes in cortical excitability with transcranial magnetic
      stimulation during 4 weeks of resistance training of the tibialis anterior
      muscle. Ten individuals performed 6 sets of 10 MVCs 3 times per week for 4 weeks
      and ten participated as a control group. There were no changes in any parameters
      tested in the control group over the 4 weeks. In the training group, TA muscle
      strength increased significantly by 10% at week 2 and by 18% at week 4. As
      hypothesized, cortical excitability during resistance training also increased.
      The amplitude of the TA surface EMG motor evoked potential elicited by TMS during
      a low-level contraction increased by 32% after training with no change in the M
      wave. These data indicate that there may be an increase in cortical excitability
      during the first few weeks of resistance training of the TA muscle.

PMID- 16891124
TI  - Volition and the idle cortex: beta oscillatory activity preceding planned and
      spontaneous movement.
AB  - Prior to the initiation of spontaneous movement, evoked potentials can be seen to
      precede awareness of the impending movement by several hundreds of milliseconds,
      meaning that this recorded neural activity is the result of unconscious
      processing. This study investigates the neural representations of impending
      movement with and without awareness. Specifically, the relationship between
      awareness and 'idling' cortical oscillations in the beta range (18-24Hz) was
      assessed. It was found that, in situations where there was awareness of the
      impending movement, pre-movement evoked potentials were associated with a
      decrease in beta range oscillations. In contrast, when awareness of the impending
      movement was not present, the onset of the pre-movement potential was associated
      with tonic levels of beta range oscillations. A model is considered where by
      distributed neural activity remains outside of conscious awareness through the
      persistence of tonic slow wave cortical oscillations.

PMID- 16891125
TI  - Caught in the act: the impact of audience on the neural response to morally and
      socially inappropriate behavior.
AB  - We examined the impact of witnesses on the neural response to moral and social
      transgressions using fMRI. In this study, participants (N=16) read short
      vignettes describing moral and social transgressions in the presence or absence
      of an audience. In line with our hypothesis, ventrolateral (BA 47) and
      dorsomedial (BA 8) frontal cortex showed increased BOLD responses to moral
      transgressions regardless of audience and to social transgressions in the
      presence of an audience relative to neutral situations. These findings are
      consistent with the suggestion that these regions of prefrontal cortex modify
      behavioral responses in response to social cues. Greater activity was observed in
      left temporal-parietal junction, medial prefrontal cortex and temporal poles to
      moral and to a lesser extent social transgressions relative to neutral stories,
      regardless of audience. These regions have been implicated in the representation
      of the mental states of others (Theory of Mind). The presence of an audience was
      associated with increased left amygdala activity across all conditions.

PMID- 16891126
TI  - Analyzing fMRI experiments with structural adaptive smoothing procedures.
AB  - Data from functional magnetic resonance imaging (fMRI) consist of time series of
      brain images that are characterized by a low signal-to-noise ratio. In order to
      reduce noise and to improve signal detection, the fMRI data are spatially
      smoothed. However, the common application of a Gaussian filter does this at the
      cost of loss of information on spatial extent and shape of the activation area.
      We suggest to use the propagation-separation procedures introduced by Polzehl,
      J., Spokoiny, V. (2006). Propagation-separation approach for local likelihood
      estimation. Probab. Theory Relat. Fields, in print. instead. We show that this
      significantly improves the information on the spatial extent and shape of the
      activation region with similar results for the noise reduction. To complete the
      statistical analysis, signal detection is based on thresholds defined by random
      field theory. Effects of adaptive and non-adaptive smoothing are illustrated by
      artificial examples and an analysis of experimental data.

PMID- 16891127
TI  - Correlation of in vitro cytotoxicity with paracellular permeability in mortal rat
      intestinal cells.
AB  - INTRODUCTION: The rat small intestinal cell line, IEC-18, was used as an in vitro
      model to differentiate between acute cytotoxicity (AC) and paracellular
      permeability (PP) of selected chemicals. METHODS: This study compares the low
      resistance rat intestinal mortal cell line, IEC-18 (transepithelial electrical
      resistance, TEER=160+/-10 Omega cm(2)) with the high resistance human intestinal
      cell line, Caco-2 (TEER=900+/-100 Omega cm(2)). The two cell lines differ in
      state of differentiation, TEER and paracellular permeability characteristics. The
      IEC-18 cell line is originated from the ileum and resembles more closely the
      small intestine than the Caco-2. Cytotoxicity was carried out using MTT cell
      viability assay in 96-well plates for 24-h exposure time. PP was measured using
      TEER (membrane integrity indicator) and PP markers such as [(3)H]-D-mannitol,
      lucifer yellow (LY) and FITC-dextran (fluorescein-dextran) on cells grown on
      inserts. RESULTS: The data showed that there is a high correlation (R(2)=0.99)
      between MTT and TEER using IEC-18 cell for 24-h exposure time. IEC-18 is as
      sensitive as Caco-2 for both MTT and TEER measurements. Decrease in TEER is
      inversely proportional with increase in PP of tight junction indicators. There is
      a good correlation between IC(50)'s MTT, TEER and Registry of Cytotoxicity (RC)
      data. DISCUSSION: Based on the results from the experiments, IEC-18 can be used
      as an in vitro model to differentiate between concentrations needed for AC and
      those required for PP.

PMID- 16891128
TI  - Can intraoperative electrocorticography patterns predict surgical outcome in
      patients with temporal lobe epilepsy secondary to unilateral mesial temporal
      sclerosis?
AB  - INTRODUCTION: Intraoperative electrocorticography (ECoG) can be performed in
      cases of temporal lobe epilepsy due to hippocampal sclerosis (TLE-HS). However,
      its significance and correlation with surgical outcome are still controversial.
      OBJECTIVES: To analyze the electrophysiological characteristics of temporal lobe
      structures during ECoG of patients with TLE-HS, with emphasis on the comparison
      between pre- and post-resection recordings and surgical outcome. PATIENTS AND
      METHODS: Seventeen patients with refractory TLE-HS submitted to
      corticoamigdalohipocampectomy were included in the study. Clinical variables
      included age at the onset, duration of epilepsy and seizure outcome. The post
      operative follow-up ranged from 24 to 36 months. According to outcome subjects
      were divided in two subgroups: (A) individuals free of seizures (Engel 1A), and
      (B) individuals not-free of seizures (Engel 1B-IV). Four patterns of ECoG
      findings were identified: isolated discharges; high frequency spikes (HFS);
      continuous discharges; combination of isolated discharges and HFS. According to
      predominant topography ECoG was classified as mediobasal, lateral (or
      neocortical), mediobasal and lateral. RESULTS: The progressive removal of the
      temporal pole and the hippocampus was associated with significant decrease of
      neocortical spikes. No correlation between clinical variables and seizure outcome
      was observed. Patients who only had isolated spikes on intraoperative ECoG
      presented a statistical trend for excellent surgical control. Patients who
      presented temporal pole blurring on MRI also had better post-surgical seizure
      outcome. CONCLUSIONS: This study showed that out of diverse clinical and
      laboratory variables, only isolated discharges on intraoperative ECoG and
      temporal pole blurring on MRI predicted excellent post-surgical seizure outcome.
      However, other studies with larger number of patients are still necessary to
      confirm these findings.

PMID- 16891129
TI  - Differential cartilaginous tissue formation by human synovial membrane, fat pad,
      meniscus cells and articular chondrocytes.
AB  - OBJECTIVE: To identify an appropriate cell source for the generation of meniscus
      substitutes, among those which would be available by arthroscopy of injured knee
      joints. METHODS: Human inner meniscus cells, fat pad cells (FPC), synovial
      membrane cells (SMC) and articular chondrocytes (AC) were expanded with or
      without specific growth factors (Transforming growth factor-beta1, Fibroblast
      growth factor-2 and Platelet-derived growth factor bb, TFP) and then induced to
      form three-dimensional cartilaginous tissues in pellet cultures, or using a
      hyaluronan-based scaffold (Hyaff-11), in culture or in nude mice. Human native
      menisci were assessed as reference. RESULTS: Cell expansion with TFP enhanced
      glycosaminoglycan (GAG) deposition by all cell types (up to 4.1-fold) and
      messenger RNA expression of collagen type II by FPC and SMC (up to 472-fold)
      following pellet culture. In all models, tissues generated by AC contained the
      highest fractions of GAG (up to 1.9% of wet weight) and were positively stained
      for collagen type II (specific of the inner avascular region of meniscus), type
      IV (mainly present in the outer vascularized region of meniscus) and types I, III
      and VI (common to both meniscus regions). Instead, inner meniscus, FPC and SMC
      developed tissues containing negligible GAG and no detectable collagen type II
      protein. Tissues generated by AC remained biochemically and phenotypically stable
      upon ectopic implantation. CONCLUSIONS: Under our experimental conditions, only
      AC generated tissues containing relevant amounts of GAG and with cell phenotypes
      compatible with those of the inner and outer meniscus regions. Instead, the other
      investigated cell sources formed tissues resembling only the outer region of
      meniscus. It remains to be determined whether grafts based on AC will have the
      ability to reach the complex structural and functional organization typical of
      meniscus tissue.

PMID- 16891130
TI  - Evidence for functional ATP-sensitive (K(ATP)) potassium channels in human and
      equine articular chondrocytes.
AB  - OBJECTIVE: Chondrocytes are highly sensitive to variations in extracellular
      glucose and oxygen levels in the extracellular matrix. As such, they must possess
      a number of mechanisms to detect and respond to alterations in the metabolic
      state of cartilage. In other organs such as the pancreas, heart and brain, such
      detection is partly mediated by a family of potassium channels known as K(ATP)
      (adenosine 5'-triphosphate-sensitive potassium) channels. Here we investigate
      whether chondrocytes too express functional K(ATP) channels, which might,
      potentially, serve to couple metabolic state with cell activity. METHODS:
      Immunohistochemistry was used to explore K(ATP) channel expression in equine and
      human chondrocytes. Biophysical properties of equine chondrocyte K(ATP) channels
      were investigated with patch-clamp electrophysiology. RESULTS: Polyclonal
      antibodies directed against the K(ATP) Kir6.1 subunit revealed high levels of
      expression in human and equine chondrocytes mainly in superficial and middle
      zones of normal cartilage. Kir6.1 was also detected in superficial chondrocytes
      in osteoarthritic (OA) cartilage. In single-channel electrophysiological studies
      of equine chondrocytes, we found K(ATP) channels to have a maximum unitary
      conductance of 47 +/- 9 pS (n=5) and a density of expression comparable to that
      seen in excitable cells. CONCLUSION: We have shown, for the first time,
      functional K(ATP) channels in chondrocytes. This suggests that K(ATP) channels
      are involved in coupling metabolic and electrical activities in chondrocytes
      through sensing of extracellular glucose and intracellular adenosine triphosphate
      (ATP) levels. Altered K(ATP) channel expression in OA chondrocytes may result in
      impaired intracellular ATP sensing and optimal metabolic regulation.

PMID- 16891131
TI  - DNA synthesis in tongue keratinocytes of hepatectomized and tumor-bearing mice.
AB  - Tongue keratinocytes have high S-phase and mitotic indices with evident circadian
      variation. Transplanted tumors modify the intensity and temporal structure of the
      S-phase index in cell populations in tumor-bearing animals; also, partial
      hepatectomy changes the concentrations of substances involved in cellular
      proliferation, leading to compensatory liver hyperplasia. The aim of our study
      was to analyze the interaction between tumor growth and the liver regeneration
      that follows partial hepatectomy, and the effects of both these processes on
      lingual keratinocytes. We used 380 adult male mice divided into six groups: tumor
      free and tumor-bearing mice without surgery, with sham hepatectomy, and with
      partial hepatectomy. Each group was divided into six subgroups, which were killed
      at 4-h intervals until a circadian cycle was completed (from 26 until 50h post
      surgery in the operated animals). Each animal was injected with 5
      bromodeoxyuridine (50mg/kg) 1h before it was killed, and tongue samples were
      obtained and processed for histology. The sections were placed on silanized
      slides and incubated with the primary antibody Bu 20a (1/100 dilution). The
      reaction was developed using diaminobenzidine and staining was detected visually.
      SIs were measured as the number of labeled nuclei per thousand cells. The mean+/
      S.E. of each group was calculated. Differences among experimental groups were
      analyzed by ANOVA and the Student-Newman-Keuls Multiple Comparisons Test. The
      results show that the presence of a tumor alters the normal circadian curve of SI
      in lingual keratinocytes, irrespective of whether the mice underwent surgery.
      This finding has to be considered in drug treatments for neoplasms and in
      experiments related to growth.

PMID- 16891132
TI  - Nitric oxide-independent lipid metabolism in RAW 264.7 macrophages loaded with
      oleic acid.
AB  - The role of nitric oxide (NO) in the regulation of lipogenesis and lipolysis in
      RAW 264.7 macrophages loaded with oleic acid (OA) was investigated in this paper.
      Magnolol stimulated full lipolysis without affecting NO levels. Both inhibition
      and elevation of NO production in OA-loaded macrophages did not induce lipolysis.
      Besides, lipopolysaccharide (LPS)-induced increased accumulation of lipid
      droplets was not reduced by down-regulation of NO levels. Moreover, incubation of
      macrophages with sodium nitroprusside (SNP), an NO donor, stimulated significant
      NO production without altering the lipid droplet accumulation. All these results
      clearly demonstrate that NO is not involved in the modulation of lipid metabolism
      in macrophages loaded with OA.

PMID- 16891133
TI  - Contribution of alpha2beta1, alpha3beta1, alpha6beta4 integrins and 67 kDa
      laminin receptor to the interaction of epidermoid carcinoma A-431 cells with
      laminin-2/4.
AB  - Laminin-2/4 is the major laminin isoform of normal muscle and nerve tissues and
      plays an important role in tumor invasion and metastasis. Despite the fact that
      laminin-2/4 has been found in the skin basement membrane, insufficient evidence
      is available on the effect of laminin-2/4 on the behavior of both normal and
      transformed skin cells. A comparison of the contribution of alpha2beta1,
      alpha3beta1, alpha6beta4 integrins and 67 kDa laminin receptor on the surface of
      the human epidermoid carcinoma cell, A-431, to interaction with laminin-2/4 was
      carried out. The cell interaction with extracellular matrix component is a
      multistage process. We employed new methods for studying different stages of the
      interaction of A-431 cells with laminin-2/4. We demonstrated that integrins
      alpha2beta1, alpha3beta1, alpha6beta4 and 67 kDa laminin receptor are involved in
      the interaction of A-431 cells with laminin-2/4. We found that contribution of
      the same receptors to different stages of the interaction with laminin can be
      different. alpha2beta1 integrins are involved in EGF-induced A-431 cells'
      migration on laminin-2/4. We demonstrated the cooperation between alpha2beta1 and
      alpha3beta1 integrins during adhesion and spreading of A-431 cells on laminin-2/4
      coated substrate. These results provide information about laminin-2/4 receptors
      and their contribution to different stages of the interaction with cells.

PMID- 16891135
TI  - A new general-purpose fully automatic baseline-correction procedure for 1D and 2D
      NMR data.
AB  - A new procedure for automatic baseline correction of NMR data sets is presented.
      It is based on an improved automatic recognition of signal-free regions that uses
      a Continuous Wavelet transform derivative calculation, followed by a baseline
      modelling procedure based on the Whittaker smoother algorithm. The method has
      been proven to automatically flatten 1D and 2D NMR spectra with large baseline
      distortions arising from different sources, is tolerant to low signal-to-noise
      ratio spectra, and to signals of varying widths in a single spectrum. Even though
      this procedure has so far only been applied to NMR spectra, we believe it to also
      be applicable to other spectroscopies having relatively narrow peaks (e.g., mass
      spectrometry), and potentially to those with broad peaks (e.g., near infrared or
      ultraviolet).

PMID- 16891134
TI  - A mobile one-sided NMR sensor with a homogeneous magnetic field: the NMR-MOLE.
AB  - A new portable NMR sensor with a novel one-sided access magnet design, termed NMR
      MOLE (MObile Lateral Explorer), has been characterised in terms of sensitivity
      and depth penetration. The magnet has been designed to be portable and create a
      volume with a relatively homogeneous magnetic field, 15,000 ppm over a region
      from 4 to 16 mm away from the probe, with maximum sensitivity at a depth of 10
      mm. The proton NMR frequency is 3.3 MHz. We have demonstrated that with this
      approach a highly sensitive, portable, unilateral NMR sensor can be built. Such a
      design is especially suited for the characterisation of liquids in situations
      where unilateral or portable access is required.

PMID- 16891137
TI  - Environmental conditions, rather than season, determine torpor use and
      temperature selection in large mouse-eared bats (Myotis myotis).
AB  - We tested whether food availability, thermal environment and time of year affect
      torpor use and temperature selection in the large mouse-eared bat (Myotis myotis)
      in summer and winter. Food-deprived bats were torpid longer than bats offered
      food ad libitum. Bats placed in a gradient of low (0 degrees C-25 degrees C)
      ambient temperatures (T(a)) spent more time in torpor than bats in a gradient of
      high (7 degrees C-43 degrees C) T(a)'s. However, we did not observe seasonal
      variations in the use of torpor. Moreover, even when food deprived in winter,
      bats never entered prolonged torpor at T(a)'s characteristic of their natural
      hibernation. Instead, bats preferred shallow torpor at relatively high T(a), but
      they always maintained a difference between body and ambient temperatures of less
      than 2 degrees C. Calculations based on respirometric measurements of metabolic
      rate showed that food deprived bats spent less energy per unit of time in torpor
      than fed individuals, even when they entered torpor at higher T(a)'s. We conclude
      that T(a) likely serves as a signal of food availability and daily torpor is
      apparently an adaptation to unpredictable changes in food availability, such as
      its decrease in summer or its increase in winter. Thus, we interpret hibernation
      to be a second step in the evolution of heterothermy in bats, which allows
      survival in seasonal environments.

PMID- 16891136
TI  - Population pharmacokinetics of (R)-albuterol and (S)-albuterol in pediatric
      patients aged 4-11 years with asthma.
AB  - OBJECTIVE: To characterize the population pharmacokinetics (PK) of (R)- and (S)
      albuterol in pediatric asthmatics using a model that supports a sparse blood
      sampling strategy. METHODS: The data for this analysis were collected from
      patients enrolled in a randomized, double-blind, multicenter, placebo- and active
      controlled study evaluating the safety and efficacy of levalbuterol in asthmatic
      children aged 4-11 years. Patients received either levalbuterol 0.31 mg,
      levalbuterol 0.63 mg, racemic albuterol 1.25 mg, or racemic albuterol 2.5 mg via
      nebulizer. Separate population pharmacokinetic models were developed for (R)- and
      (S)-albuterol using the NOMNEM((R)) computer program. Covariate models were
      developed to identify significant predictors of inter-patient variability.
      RESULTS: A total of 995 samples and 262 patients were used for the (R)-albuterol
      population PK model while a total of 496 samples and 128 patients were used for
      the (S)-albuterol population PK model. The apparent clearance of (R)-albuterol
      was much more rapid than that of (S)-albuterol (approximately four-fold higher),
      and the apparent volume of distribution was much larger for (R)-albuterol (in
      part due to pre-systemic metabolism) than for (S)-albuterol (approximately four
      fold higher). CONCLUSIONS: In this study of pediatric patients, the models were
      able to demonstrate using two to four samples per patient that the apparent
      clearance and volume of distribution of (R)-albuterol were several fold higher
      than that of (S)-albuterol. The pharmacokinetics of (R)-albuterol were similar
      after administration of levalbuterol or racemic albuterol and were linear over
      the examined dose range (0.31-0.63 mg nebulized dose). The presence of (S)
      albuterol did not significantly alter the pharmacokinetics of (R)-albuterol,
      suggesting that effects of (S)-albuterol may be due to the intrinsic pharmacology
      of this isomer.

PMID- 16891138
TI  - Distribution of retinylester-storing stellate cells in the arrowtooth halibut,
      Atheresthes evermanni.
AB  - Hepatic stellate cells play a major role in retinylester storage in mammals, but
      the retinoid-storing state in nonmammalian vertebrates remains to be elucidated.
      In this study, we examined retinoids and retinoid-storing cells in the arrowtooth
      halibut, Atheresthes evermanni. High-performance liquid chromatography analyses
      revealed the highest concentrations of stored retinoids (retinol and
      retinylester, 6199 nmol/g) in the pyloric cecum, a teleost-specific organ
      protruding from the intestine adjacent to the pylorus. Considerable amounts of
      retinoids were also stored in the intestine (3355 nmol/g) and liver (1891
      nmol/g), and small amounts in the kidney (102 nmol/g). Very small amounts or no
      retinoids were detected in the heart, gill, skeletal muscle, and gonads (less
      than 2 nmol/g). Use of gold chloride staining and fluorescence microscopy to
      detect retinoid autofluorescence showed that, in the pyloric cecum and intestine,
      retinoid-storing cells were localized in the lamina propria mucosae. Under
      electron microscopy, cells containing well-developed lipid droplets, which are
      common morphological characteristics of the hepatic stellate cells of mammals,
      were observed in the lamina propria mucosae of the pyloric cecum. Thus, the
      distribution of stellate cells with retinoid-storing capacity differs between
      this halibut and mammals, suggesting that the retinoid-storing site has shifted
      during vertebrate evolution.

PMID- 16891139
TI  - Muscle delta13C change in Nile tilapia (Oreochromis niloticus): effects of growth
      and carbon turnover.
AB  - The contribution of growth and turnover to the muscle delta(13)C change process
      was investigated using mathematical models which associate delta(13)C change to
      time of intake of a new diet or increase in body mass. Two groups of Nile tilapia
      (Oreochromis niloticus) were fed on diets based on C3 (delta(13)C=-25.64+/-0.06
      per thousand) or C4 (delta(13)C=-16.01+/-0.06 per thousand) photosynthetic cycle
      plants to standardize the muscle delta(13)C. After establishing the carbon
      isotopic equilibrium, fish (mean mass 24.12+/-6.79 g) then received the other
      treatment diet until a new carbon isotopic equilibrium could be established,
      characterizing T1 (C3-C4) and T2 (C4-C3) treatments. No significant differences
      were observed in fish productive performance. Good fits were obtained for the
      models that associated the delta(13)C change to time, resulting in carbon half
      life values of 23.33 days for T1 and 25.96 days for T2. Based on values found for
      the muscle delta(13)C change rate from growth (0.0263 day(-1) and 0.0254 day(-1))
      and turnover (0.0034 day(-1) and 0.0013 day(-1)), our results indicate that most
      of the delta(13)C change could be attributed to growth. The application of model
      that associated the delta(13)C change to body mass increase seems to produce
      results with no apparent biological explanation. The delta(13)C change rate could
      directly reflect the daily ration and growth rate, and consequently the isotopic
      change rates of carbon and other tissue elements can be properly used to assess
      different factors that may interfere in nutrient utilization and growth.

PMID- 16891140
TI  - Physiological and genetic engineering of cytosolic redox metabolism in
      Saccharomyces cerevisiae for improved glycerol production.
AB  - Previous metabolic engineering strategies for improving glycerol production by
      Saccharomyces cerevisiae were constrained to a maximum theoretical glycerol yield
      of 1 mol.(molglucose)(-1) due to the introduction of rigid carbon, ATP or redox
      stoichiometries. In the present study, we sought to circumvent these constraints
      by (i) maintaining flexibility at fructose-1,6-bisphosphatase and triosephosphate
      isomerase, while (ii) eliminating reactions that compete with glycerol formation
      for cytosolic NADH and (iii) enabling oxidative catabolism within the
      mitochondrial matrix. In aerobic, glucose-grown batch cultures a S. cerevisiae
      strain, in which the pyruvate decarboxylases the external NADH dehydrogenases and
      the respiratory chain-linked glycerol-3-phosphate dehydrogenase were deleted for
      this purpose, produced glycerol at a yield of 0.90 mol.(molglucose)(-1). In
      aerobic glucose-limited chemostat cultures, the glycerol yield was ca. 25% lower,
      suggesting the involvement of an alternative glucose-sensitive mechanism for
      oxidation of cytosolic NADH. Nevertheless, in vivo generation of additional
      cytosolic NADH by co-feeding of formate to aerobic, glucose-limited chemostat
      cultures increased the glycerol yield on glucose to 1.08 mol mol(-1). To our
      knowledge, this is the highest glycerol yield reported for S. cerevisiae.

PMID- 16891141
TI  - Regional community-acquired urinary tract infections in Israel: diagnosis,
      pathogens, and antibiotic guidelines adherence: a prospective study.
AB  - INTRODUCTION: The identification and treatment of hospitalized patients with
      community-acquired urinary tract infections (CAUTI) may be a challenge. The
      pathogens causing the infection and their relative proportions vary
      geographically and with time. This observational prospective study had three
      primary goals: (1) to estimate the likelihood of diagnosis of CAUTI upon
      admission; (2) to evaluate adherence to the institutional recommendations; (3) to
      assess the compatibility of the current local antibiotic recommendations with a
      pathogen's distribution and with its drug sensitivities. METHODS AND RESULTS: Two
      hundred and twenty-three patients with positive urinary cultures fulfilling
      criteria for CAUTI were studied. Only 54 (24.2%) were diagnosed as having a
      urinary tract infection upon admission. Approximately 90% of the patients, who
      were correctly diagnosed, received the institutional recommended antibiotic
      therapy (ofloxacin or cefuroxime). Gram-negative intestinal flora comprised 86.1%
      (192 patients) of the causative microorganisms. Of these, 20.3% of the pathogens
      demonstrated resistance to ofloxacin and 19.8% to cefuroxime. The prevalence of
      Escherichia coli, the most common pathogen of UTI, significantly declined in the
      current study, from 70.5% in 1991 to 56% in 2000. CONCLUSIONS: We observed a low
      sensitivity in diagnosing community-acquired urinary tract infections upon
      admission. In patients correctly diagnosed, the use of recommended antibiotics
      was high. A substantial percentage of the pathogens were resistant to the
      recommended antibiotics. This study stresses the need for frequent re-evaluation
      of the prevalence of pathogens involved in regional community-acquired urinary
      tract infections and the adjustment of the empirical first-line treatment
      accordingly.

PMID- 16891143
TI  - [Spontaneous rupture of the uterine pedicle during pregnancy: Three case
      reports].
AB  - We report a retrospective review of three cases presenting with spontaneous
      uterine artery rupture during pregnancy. Clinical presentations were intra
      peritoneal haemorrhage for two of them and in utero fetal death for the last one.
      Fetal outcome was poor in all three cases. Uterine vessels spontaneous rupture
      during pregnancy is an exceptional event. Considering our experience and the
      literature review, we propose a guideline for vascular rupture during pregnancy.

PMID- 16891142
TI  - [High precision radiotherapy with ultrasonic imaging guidance].
AB  - Conformal radiation therapy with or without intensity modulation is the standard
      treatment of localized prostate cancer and facilitates dose escalation. The
      implementation of three-dimensional conformal radiotherapy necessitates focusing
      on target volume delineation, dosimetry, reproducibility of treatment and quality
      control. Recently, ultrasound systems that allow direct daily visualization of
      the prostate have become available. This non-invasive technique can be used to
      correct both prostate organ motion and set-up error and leads to increase
      treatment accuracy.

PMID- 16891144
TI  - Findings of interest from immunology and psychoneuroimmunology.
AB  - The biopsychosocial paradigm is now the main model when dealing with most human
      health disorders. One of the strengths of this model is that it encourages
      broader thinking when assessing and managing patients. It also encourages broader
      reading into areas not traditionally associated with manual therapy. Immunology
      and neuroscience are amongst the fastest growing medical sciences. These fields
      come together in the relatively new area of psychoneuroimmunolgy. This article
      examines some findings from these fields that are not widely discussed in the
      physical therapy professions. These findings are of relevance to many of the
      disciplines within the physical therapies. It is the authors aim to stimulate
      further interest in the relevant, yet often under explored areas of immunology
      and psychoneuroimmunology.

PMID- 16891145
TI  - Mechanical Diagnosis and Therapy approach to assessment and treatment of
      derangement of the sacro-iliac joint.
AB  - This case report describes the clinical reasoning and management of the
      sacroiliac joint, utilising the McKenzie Method of Mechanical Diagnosis and
      Therapy (MDT). A patient with a 2 year history of buttock and thigh pain
      demonstrates a directional preference for repeated anterior SIJ rotation. The MDT
      approach is discussed and is an ideal method for emphasising the patients
      involvement in managing their own back problem.

PMID- 16891146
TI  - Location of the cell-binding domain of CP65, a 65kDa cysteine proteinase involved
      in Trichomonas vaginalis cytotoxicity.
AB  - The cysteine proteinase (CP) of 65kDa, CP65, binds to the surface of HeLa cells
      and is involved in Trichomonas vaginalis cellular damage. To identify and locate
      the CP65 cellular-binding domain, we enriched the CP65 protein band by ammonium
      sulfate fractionation and ion-exchange chromatography and the N-terminal sequence
      was obtained. A 618bp gene fragment was obtained by PCR using genomic DNA as
      template and primers derived from the N-terminal sequence of CP65 and the Asn
      papain-catalytic conserved region. This gene fragment encodes for 206 amino acid
      (aa) residues corresponding to the N-terminal region of a mature CP with 67-76%
      identity to the reported trichomonad cathepsin-L-like CPs. This gene fragment was
      expressed in a bacterial system for antibody production and functional analysis.
      Antibodies against the native trichomonad CP65 recognized the recombinant
      protein, referred to as rCP65, confirming its relationship with the CP65 gene.
      The rCP65 protein was bound to the surface of HeLa cells and competed with the
      native CP65 for binding. Antibodies to the rCP65 (alpha-rCP65) reacted with the
      trichomonad CP65 located on the parasite surface, and inhibited trichomonal
      cytotoxicity in a concentration-dependent manner. These data strongly suggest
      that this gene fragment encodes for the putative cell-binding domain (CBD) of
      CP65 located at its N-terminal region.

PMID- 16891148
TI  - Plant volatiles: a lack of function or a lack of knowledge?

PMID- 16891149
TI  - Clinical evaluation of the intraoral fluoride releasing system in radiation
      induced xerostomic subjects. Part 1: Fluorides.
AB  - Radiation-induced xerostomia results in significant changes in the oral cavity
      particularly oral microbial changes, which include a marked increase in the
      number of cariogenic organisms, notably Streptococcus mutans and lactobacillus
      species. This loss of the capacity to secrete saliva creates or promotes the
      rapid onset and progression of rampant dental caries. In this 2-part series, the
      benefit of fluoride in reducing caries activity is presented. Part 1 discusses
      the historical and currently available fluoride preparations and Part 2 presents
      data of a recently completed trial investigating the benefit of an intraoral
      sodium fluoride releasing system.

PMID- 16891151
TI  - Metal complexes of Schiff base derived from sulphametrole and o-vanilin.
      Synthesis, spectral, thermal characterization and biological activity.
AB  - Metal complexes of Schiff base derived from condensation of o-vanilin (3
      methoxysalicylaldehyde) and sulfametrole [N(1)-(4-methoxy-1,2,5-thiadiazole-3
      yl)sulfanilamide] (H2L) are reported and characterized based on elemental
      analyses, IR, 1H NMR, solid reflectance, magnetic moment, molar conductance, mass
      spectra, UV-vis and thermal analysis (TGA). From the elemental analyses data, the
      complexes were proposed to have the general formulae [M2X3(HL)(H2O)5].yH2O (where
      M=Mn(II), Co(II), Ni(II), Cu(II), Zn(II) and Cd(II), X=Cl, y=0-3);
      [Fe2Cl5(HL)(H2O)3].2H2O; [(FeSO4)2(H2L)(H2O)4] and [(UO2)2(NO3)3(HL)(H2O)].2H2O.
      The molar conductance data reveal that all the metal chelates were non
      electrolytes. The IR spectra show that, H2L is coordinated to the metal ions in a
      tetradentate manner with ON and NO donor sites of the azomethine-N, phenolic-OH,
      enolic sulphonamide-OH and thiadiazole-N. From the magnetic and solid reflectance
      spectra, it is found that the geometrical structures of these complexes are
      octahedral. The thermal behaviour of these chelates shows that the hydrated
      complexes losses water molecules of hydration in the first step followed
      immediately by decomposition of the anions and ligand molecules in the subsequent
      steps. The activation thermodynamic parameters, such as, E*, DeltaH*, DeltaS* and
      DeltaG* are calculated from the DrTG curves using Coats-Redfern method. The
      synthesized ligand, in comparison to their metal complexes also were screened for
      their antibacterial activity against bacterial species, Escherichia coli,
      Salmonella typhi, Bacillus subtillus, Staphylococcus aureus and Fungi
      (Aspergillus terreus and Aspergillus flavus). The activity data show that the
      metal complexes to be more potent/antimicrobial than the parent Shciff base
      ligand against one or more microbial species.

PMID- 16891152
TI  - Cardiac resynchronization therapy increases plasma levels of the endogenous
      inotrope apelin.
AB  - BACKGROUND: Cardiac resynchronization therapy (CRT) has been introduced to treat
      drug refractory chronic heart failure (CHF). Apelin, the endogenous ligand of the
      APJ receptor, is under evaluation for its potential role in human CHF
      pathophysiology. This study aims to assess whether biventricular pacing affects
      plasma apelin levels in patients with severe CHF. METHODS AND RESULTS: Fourteen
      patients (9 men, 5 women, mean age 68+/-13 years) undergoing biventricular pace
      maker/ICD implantation were studied. Patients underwent baseline clinical and
      echocardiographic evaluation, and assessment of plasma apelin and NT-proBNP
      levels. The evaluation was repeated 48 h and 9+/-2 months after device
      implantation to assess the acute and chronic effects of CRT on apelin and NT
      proBNP levels. Eight healthy age- and sex-matched subjects served as controls. In
      CHF patients, baseline apelin levels were reduced and NT-proBNP increased
      compared to control subjects (apelin: 0.47+/-0.2 vs. 0.97+/-0.3 ng/mL, p<0.001;
      NT-proBNP: 2007+/-114 vs. 229+/-72 pmol/L, p<0.001). Short-term evaluation did
      not reveal any effect of CRT on apelin or NT-proBNP levels. By contrast, at 9+/-2
      months follow-up, CRT responders showed left ventricular reverse remodelling and
      an increase in ejection fraction, together with a significant increase in plasma
      apelin levels (0.99+/-0.1 vs. 0.47+/-0.2 ng/mL, p<0.001) and decrease in NT
      proBNP (938+/-591 vs. 2007+/-114 pmol/L, p<0.05). CONCLUSIONS: Long-term CRT
      increases plasma levels of the endogenous inotrope apelin in patients with CHF.

PMID- 16891153
TI  - Early stages of human plasma proteins adsorption probed by Atomic Force
      Microscope.
AB  - Atomic Force Microscope (AFM) as a surface characterization technique has offered
      a great impulse in the advance of biocompatible materials. In this study AFM was
      implemented for the investigation of the early stages of adsorption of two human
      plasma proteins on titanium and hydrogenated carbon biocompatible thin films. The
      plasma proteins that were used were Human Serum Albumin and Fibrinogen, two of
      the most important proteins in human plasma. The concentration of the protein
      solutions was the same as that in human plasma. As the examined samples were
      soft, non-contact AFM mode was used to avoid their destruction. In order for the
      early stages of protein adsorption to be assessed, small incubation times were
      applied. AFM measurements in liquid buffer were also carried out, allowing the
      observation of the protein behaviour in an environment much closer to their
      native one. In addition, there was an assessment of the adsorption mechanism of
      the proteins on the above-mentioned biomaterials.

PMID- 16891154
TI  - Hydrogen plasma surface activation of silicon for biomedical applications.
AB  - Silicon has gradually been recognized to be an essential trace element in the
      normal metabolism of higher animals, and the role of silicon in the human body
      has aroused interests in the biomedical community. In fact, the interactions
      between silicon-based devices and the human body such as biosensors and
      microelectromechanical systems (MEMS) often suffer from poor biocompatibility. In
      this work, hydrogen plasma immersion ion implantation (H-PIII) is conducted to
      improve the bioactivity or bone conductivity of silicon. In order to investigate
      the formation mechanism of bone-like apatite on the surface of the hydrogen
      implanted silicon wafer, two comparative experiments, hydrogenation and argon
      bombardment, are performed. The H-PIII sample exhibits an amorphous surface
      consisting of Si-H bonds. After immersion in simulated body fluids, a negatively
      charged surface containing the functional group ([triple bond]Si-O-) is produced
      and bone-like apatite is observed to nucleate and grow on the surface. The
      surface of the H-PIII silicon wafer favors the adhesion and growth of osteoblast
      cells and good cytocompatibility may be inferred.

PMID- 16891155
TI  - Hatena arenicola gen. et sp. nov., a katablepharid undergoing probable plastid
      acquisition.
AB  - Hatena arenicola gen. et sp. nov., an enigmatic flagellate of the katablepharids,
      is described. It shows ultrastructural affinities to the katablepharids,
      including large and small ejectisomes, cell covering, and a feeding apparatus.
      Although molecular phylogenies of the 18S ribosomal DNA support its
      classification into the katablepharids, the cell is characterized by a
      dorsiventrally compressed cell shape and a crawling motion, both of which are
      unusual within this group. The most distinctive feature of Hatena arenicola is
      that it harbors a Nephroselmis symbiont. This symbiosis is distinct from
      previously reported cases of ongoing symbiosis in that the symbiont plastid is
      selectively enlarged, while other structures such as the mitochondria, Golgi
      body, cytoskeleton, and endomembrane system are degraded; the host and symbiont
      have developed a morphological association, i.e., the eyespot of the symbiont is
      always at the cell apex of Hatena arenicola; and only one daughter cell inherits
      the symbiont during cell division, resulting in a symbiont-bearing green cell and
      a symbiont-lacking colorless cell. Interestingly, the colorless cells have a
      feeding apparatus that corresponds to the location of the eyespot in symbiont
      bearing cells, and they are able to feed on prey cells. This indicates that the
      morphology of the host depends on the presence or absence of the symbiont. These
      observations suggest that Hatena arenicola has a unique "half-plant, half
      predator" life cycle; one cell divides into an autotrophic cell possessing a
      symbiotic Nephroselmis species, and a symbiont-lacking colorless cell, which
      later develops a feeding apparatus de novo. The evolutionary implications of
      Hatena arenicola as an intermediate step in plastid acquisition are discussed in
      the context of other examples of ongoing endosymbioses in dinoflagellates.

PMID- 16891156
TI  - Prevalence of virulence genes (ctxA, stn, OmpW and tcpA) among non-O1 Vibrio
      cholerae isolated from fresh water environment.
AB  - The virulence of a pathogen is reliant on the presence of a discrete set of
      genetic determinants and their expression in the host. The virulence of Vibrio
      spp. is regulated by the ctxAB and tcpA genes. These genes are alleged to be
      exclusively associated with clinical strains of O1 and O139 serogroups. In the
      present study, we examined the presence of virulence genes viz. stn, OmpW, ctxA
      and tcpA of classical and ElTor variants, in environmental strains of non-O1
      Vibrio cholerae cultured seasonally from four sampling stations of the river
      Narmada at Jabalpur (MP), India. Unexpectedly, the PCR analysis of the strains
      revealed the presence of these genes among environmental V. cholerae. The strains
      harboring the tcpA gene also carried the ctxA gene. Sequencing of the tcpA gene
      and ctxA gene carried by an environmental strain showed approximately 97%
      homology with the previously sequenced genes submitted in the GenBank. We report
      here the prevalence of cholera toxin gene and the gene for toxin co-regulated
      pilus among non-O1 V. cholerae strains isolated from fresh water environment.
      This study supports the idea that cholera toxin has an environmental derivation
      and that the intricate aquatic environment can give rise to pathogenic Vibrio
      organisms.

PMID- 16891157
TI  - Psychiatric symptoms in adolescents with epilepsy in junior high school in
      Norway: a population survey.
AB  - The aims of this study were to assess the frequency and impact of psychiatric
      symptoms among adolescents with epilepsy in a general population, and compare the
      findings with those for adolescents without epilepsy. The data were collected
      through the Health Profiles for Children and Youth in Akershus Study. The data
      were cross-sectional and based on self-reports from adolescents (13-16 years of
      age). To assess psychiatric symptoms, we used the Strengths and Difficulties
      Questionnaire-Self Report (SDQ-S). A total of 11,021 pupils were invited to
      participate, and 9424 responded to the questionnaire (response rate=86%). We
      found that adolescents with epilepsy (124) from an unselected group obtained a
      significantly higher symptom score on the SDQ-S than those without epilepsy,
      indicating a higher incidence of psychiatric symptoms. The adolescents with
      epilepsy also reported a greater impact of their perceived difficulties on their
      daily life than did adolescents without epilepsy. The study illustrates the need
      for developing better strategies to detect and prevent psychiatric problems in
      adolescents with epilepsy.

PMID- 16891158
TI  - Urinary bladder urothelium: molecular sensors of chemical/thermal/mechanical
      stimuli.
AB  - The identification of functional receptors/ion channels in bladder urothelial
      cells and the involvement of these sensor molecules in the release of chemical
      mediators (nitric oxide, NO; ATP) suggest that urothelial cells exhibit
      specialized sensory and signaling properties. Such mechanisms could allow these
      cells to respond to their chemical and physical environments and to engage in
      reciprocal communication with neighboring urothelial cells as well as nerves in
      the bladder wall. These and other findings highlight the functional importance of
      the urinary bladder urothelium and suggest that perturbations in urothelial
      targets and/or cell-cell interactions may lead to a number of urinary tract
      abnormalities.

PMID- 16891160
TI  - Molecularly imprinted solid-phase extraction for rapid screening of mycophenolic
      acid in human plasma.
AB  - A molecularly imprinted solid-phase extraction coupled with high performance
      liquid chromatography (MISPE-HPLC) method was developed for rapid screening of
      mycophenolic acid (MPA) in human plasma. MPA imprinted polymers (MPA-MIP) were
      synthesized and then tested for their performance both in organic and in aqueous
      solution. MPA was selectively trapped and preconcentrated on the MPA-MIP sorbent
      using different loading and washing conditions. The good selectivity of MPA-MIP
      enabled further clean-up of the interfering components in human plasma. For the
      proposed MISPE-HPLC method, the linearity between responses (peak area) and
      concentration was found over the range of 1-100microg/ml with a linear regression
      coefficient (R(2)) of 0.9989. The limit of detection (LOD) and theoretical limit
      of quantification (LOQ) for MPA in plasma were 0.10 and 0.32microg/ml,
      respectively. The precisions were 7.3, 3.5 and 4.7% RSD for intra-day assay and
      9.2, 4.1 and 5.5% RSD for inter-day reproducibility, respectively, at three
      concentration levels of MPA in spiked plasma (1, 10 and 100microg/ml). Both
      recoveries for the extraction (more than 74%) and for the analytical method (more
      than 87%) were acceptable for screening MPA in plasma samples. Twelve-hour
      pharmacokinetic profile of MPA for a renal transplant recipient receiving chronic
      oral dosing of 500mg mycophenolate mofetil (MMF) was investigated. Results
      indicated that this method could be applied for therapeutic drug monitoring of
      mycophenolic acid in patient plasma.

PMID- 16891159
TI  - Short-term stability of testosterone and epitestosterone conjugates in urine
      samples: quantification by liquid chromatography-linear ion trap mass
      spectrometry.
AB  - A simple method using liquid chromatography-linear ion trap mass spectrometry for
      simultaneous determination of testosterone glucuronide (TG), testosterone sulfate
      (TS), epitestosterone glucuronide (EG) and epitestosterone sulfate (ES) in urine
      samples was developed. For validation purposes, a urine containing no detectable
      amount of TG, TS and EG was selected and fortified with steroid conjugate
      standards. Quantification was performed using deuterated testosterone conjugates
      to correct for ion suppression/enhancement during ESI. Assay validation was
      performed in terms of lower limit of detection (1-3ng/mL), recovery (89-101%),
      intraday precision (2.0-6.8%), interday precision (3.4-9.6%) and accuracy (101
      103%). Application of the method to short-term stability testing of urine samples
      at temperature ranging from 4 to 37 degrees C during a time-storage of a week
      lead to the conclusion that addition of sodium azide (10mg/mL) is required for
      preservation of the analytes.

PMID- 16891161
TI  - Confirmation of diminazene diaceturate in bovine plasma using electrospray liquid
      chromatography-mass spectrometry.
AB  - Diminazene diaceturate is used as a trypanocide for cattle in tropical regions.
      This paper describes a LC-MS(n) method to confirm the presence of diminazene in
      bovine plasma. Bound diminazene in plasma samples was freed with dilute
      phosphoric acid, then concentrated on a bonded C(18) SPE cartridge. The LC-MS(n)
      method utilized electrospray ionization coupled with an ion trap mass
      spectrometer. Ions observed in MS(2) and MS(3) product ion spectra, as well as
      those from the MS(1) spectrum, were monitored. The method was validated with
      plasma samples fortified with diminazene diaceturate (4-100ng/mL). Diminazene was
      confirmed in samples fortified with diminazene diaceturate at levels of 6.4ng/mL
      or higher.

PMID- 16891162
TI  - Microarray-based gene expression profiling to elucidate cellular responses to
      nitric oxide--a review from an analytical and biomedical point of view.
AB  - Nitric oxide (NO) produced by NO synthases (NOS) regulates a wide range of
      cellular functions. Analysis by gene arrays provides valuable information for
      identifying important elements of the cellular responses to NO. Such screening
      tools might be useful to elucidate NO-responsive regulators, which play a central
      role in mediating NO effects. Although the final importance of a particular gene
      is determined by the encoded protein and further protein modifications,
      measurements of RNA levels have proven to be partly valuable in identifying the
      molecular changes that occur in cells. Microarray technology permits large-scale
      and genome-wide analysis of gene expression from multiple samples. We review the
      current knowledge of the use of microarray gene expression screening in
      elucidating the effects of NO on various cells and tissues. We also point out the
      limitations of general microarray-based gene expression analyses and especially
      when investigating the effects of NO.

PMID- 16891163
TI  - Liquid chromatography-tandem mass spectrometric determination of ceramides and
      related lipid species in cellular extracts.
AB  - A liquid chromatography-electrospray ionization tandem mass spectrometric (LC
      MS/MS) method was developed for the simultaneous qualitative and quantitative
      determination of sphingolipid metabolites such as ceramides, sphingisine,
      sphinganine, sphingomyelins, and ceramide 1-phosphates in the extracts of human
      promyelocytic leukemia cells (HL-60). The assay uses C(4) ceramide as an internal
      standard; simple liquid extraction; a short XTerra MS C(18) (3 microm, 50 mm x2.0
      mm) column; a gradient mobile phase of 5mM ammonium formate (pH
      4.0)/methanol/tetrahydrofuran (5/2/3-->1/2/7); mass spectrometric detection using
      electrospray ionization. This LC-MS/MS method allowed the identification of 22
      sphingolipid derivatives at pmol levels. In addition, this technique was
      successfully applied to analyze the changes of the sphingolipids profiles in
      cancer cells treated with apoptosis inducing agents, C(2) ceramide and H(2)O(2).

PMID- 16891164
TI  - Aqueous-aqueous two-phase systems composed of low molecular weight of
      polyethylene glycols and dextrans for counter-current chromatographic
      purification of proteins.
AB  - New aqueous-aqueous two-phase systems composed of relatively low molecular weight
      polymers such as polyethylene glycol (PEG) (Mr: 1000-4000) and dextran (Mr:
      10,000 and 40,000) were evaluated for purification of proteins by counter-current
      chromatography (CCC). The compositions of aqueous two-phase systems were
      optimized by measuring parameters such as viscosity and volume ratio between the
      two phases. CCC purification of a glucosyltransferase (GTF) from Streptococcus
      mutans (SM) cell-lysate was successfully demonstrated with a 7.5% PEG 3350-10%
      dextran T40 system containing 10mM potassium phosphate buffer at pH 9.0. After
      CCC purification, both PEG and dextran contained in the CCC fractions were easily
      removed by ultrafiltration in a short period of time. The fractionated column
      contents containing GTF were analyzed by enzymatic activity as well as sodium
      dodecyl sulfate (SDS) polyacrylamide gel electrophoresis. The recovery of the
      enzyme from CCC fraction was over 95% as estimated by enzymatic activities.

PMID- 16891165
TI  - An insight into the mechanism of protein separation by colloidal gas aphrons
      (CGA) generated from ionic surfactants.
AB  - Colloidal gas aphrons (CGA), which are surfactant stabilised microbubbles, have
      been previously applied for the recovery of proteins from model mixtures and a
      few studies have demonstrated the potential of these dispersions for the
      selective recovery of proteins from complex mixtures. However there is a lack of
      understanding of the mechanism of separation and forces governing the selectivity
      of the separation. In this paper a mechanistic study is carried out to determine
      the main factors and forces influencing the selectivity of separation of whey
      proteins with CGA generated from ionic surfactants. Two different separation
      strategies were followed: (i) separation of lactoferrin and lactoperoxidase by
      anionic CGA generated from a solution of sodium bis-(2-ethyl hexyl)
      sulfosuccinate (AOT); (ii) separation of beta-lactoglobulin by cationic CGA
      generated from a solution of cetyltrimethylammonium bromide (CTAB). Separation
      results indicate that electrostatic interactions are the main forces determining
      the selectivity however these could not completely explain the selectivities
      obtained following both strategies. Protein-surfactant interactions were studied
      by measuring the zeta potential changes on individual proteins upon addition of
      surfactant and at varying pH. Interestingly strongest electrostatic interactions
      were measured at those pH and surfactant to protein mass ratios which were
      optimum for protein separation. Effect of surfactant on protein conformation was
      determined by measuring the change in fluorescence intensity upon addition of
      surfactant at varying pH. Differences in the fluorescence patterns were detected
      among proteins which were correlated to differences in their conformational
      features which could in turn explain their different separation behaviour. The
      effect of conformation on selectivity was further proven by experiments in which
      conformational changes were induced by pre-treatment of whey (heating) and by
      storage at 4 degrees C. Overall it can be concluded that separation of proteins
      by ionic CGA is driven mainly by electrostatic interactions however
      conformational features will finally determine the selectivity of the separation
      with competitive adsorption having also an effect.

PMID- 16891166
TI  - Analytical methodologies for the detection and structural characterization of
      phosphorylated proteins.
AB  - Phosphorylation of proteins is a frequent post-translational modification
      affecting a great number of fundamental cellular functions in living organisms.
      Because of its key role in many biological processes, much effort has been spent
      over the time on the development of analytical methodologies for characterizing
      phosphoproteins. In the past decade, mass spectrometry-based techniques have
      emerged as a viable alternative to more traditional methods of phosphorylation
      analysis, providing accurate information for a purified protein on the number of
      the occurring phosphate groups and their exact localization on the polypeptide
      sequence. This review summarizes the analytical methodologies currently available
      for the analysis of protein phosphorylation, emphasizing novel mass spectrometry
      (MS) technologies and dedicated biochemical procedures that have been recently
      introduced in this field. A formidable armamentarium is now available for
      selective enrichment, exaustive structural characterization and quantitative
      determination of the modification degree for phosphopeptides/phosphoproteins.
      These methodologies are now successfully applied to the global analysis of
      cellular proteome repertoire according a holistic approach, allowing the
      quantitative study of phosphoproteomes on a dynamic time-course basis. The
      enormous complexity of the protein phosphorylation pattern inside the cell and
      its dynamic modification will grant important challenges to future scientists,
      contributing significantly to deeper insights into cellular processes and cell
      regulation.

PMID- 16891168
TI  - Prokaryotic DNA mismatch repair.

PMID- 16891169
TI  - Pleiotropic effects of phosphatidylinositol 3-kinase in monocyte cell regulation.

PMID- 16891170
TI  - Selenocysteine incorporation machinery and the role of selenoproteins in
      development and health.

PMID- 16891171
TI  - Indirect readout of DNA sequence by proteins: the roles of DNA sequence-dependent
      intrinsic and extrinsic forces.

PMID- 16891173
TI  - Regulation of L-histidine decarboxylase and its role in carcinogenesis.

PMID- 16891174
TI  - Eukaryotic initiation factor 2B and its role in alterations in mRNA translation
      that occur under a number of pathophysiological and physiological conditions.

PMID- 16891176
TI  - The case for mRNA 5' and 3' end cross talk during translation in a eukaryotic
      cell.

PMID- 16891177
TI  - Interferon action and the double-stranded RNA-dependent enzymes ADAR1 adenosine
      deaminase and PKR protein kinase.

PMID- 16891178
TI  - Establishment and regulation of chromatin domains: mechanistic insights from
      studies of hemoglobin synthesis.

PMID- 16891179
TI  - Detecting the unusual: natural killer cells.

PMID- 16891175
TI  - Role of protein tyrosine phosphatases in cancer.

PMID- 16891172
TI  - Repair of topoisomerase I-mediated DNA damage.

PMID- 16891189
TI  - Translational research involving new biomarkers of disease: a leading role for
      pathologists.

PMID- 16891190
TI  - Effects of storage time and exogenous protease inhibitors on plasma protein
      levels.
AB  - Plasma biomarker analysis requires intact unbiased starting material. We analyzed
      the effects on plasma protein profiles of protease inhibitor cocktails and
      preprocessing storage. Plasma from 12 healthy subjects collected with and without
      protease inhibitors was prepared immediately and after 2 hours of room
      temperature storage. The samples were analyzed by a multiplexed enzyme-linked
      immunosorbent assay that captured 99 chemokines and cytokines. Unsupervised
      hierarchical analysis clustered the samples into 4 groups; one composed
      predominantly of samples processed immediately, another of samples processed
      after 2 hours, and the remaining two were a mix of immediate and 2-hour samples.
      The mixed and immediate group protein profiles were similar. However, among the
      immediate and 2-hour samples, the levels of 37 factors differed significantly:
      all were greater after 2 hours. The dramatic changes in protein levels during
      storage were independent of protease inhibitors and are likely due to cytokine
      production and/or release by leukocytes and platelets.

PMID- 16891191
TI  - Measurement of a plasma stroke biomarker panel and cardiac troponin T in marathon
      runners before and after the 2005 Boston marathon.
AB  - We report changes in cardiac troponin-T (TnT) and a new plasma stroke biomarker
      panel (D-dimer, B-natriuretic peptide [BNP], matrix metalloproteinase-9 [MMP-9],
      S-100 b, Biosite Diagnostics, San Diego, CA) in 30 nonprofessional marathon
      runners before and immediately after the 2005 Boston Marathon. Following
      competition, there was a statistically significant increase in MMP-9 (P < .001)
      and D dimer (P < .001). Nonsignificant changes in S-100 b and BNP were observed.
      Premarathon and postmarathon values for a multimarker stroke index increased from
      0.97 (normal) to 3.5 (low risk or more; P < .001). Two subjects had index values
      more than the high-risk cutoff value. Mean TnT premarathon and postmarathon
      levels increased (from <0.01 to 0.03 ng/mL; P < .0001). After the marathon, with
      a cutoff value of 0.05 ng/mL, 7 runners (23%) had values above the manufacturer's
      recommended cutoff for myocardial damage. Although biochemical evidence of
      myocardial damage following strenuous exercise may reflect myocardial stunning or
      subclinical ischemia, the changes in the stroke index and values for individual
      stroke markers may reflect a systemic inflammatory response to exertional
      rhabdomyolysis which is common, but the possibility of subclinical central
      nervous system damage cannot be excluded.

PMID- 16891192
TI  - Evaluation of a protocol to control utilization of B-type natriuretic peptide
      testing.
AB  - The Veterans Affairs (VA) Boston Healthcare System, Boston, MA, instituted a
      protocol limiting the number of B-type natriuretic peptide (BNP) assays to 1 per
      hospitalization or outpatient visit and requiring approval of the cardiology
      service for more than 1 because of a 3-fold monthly increase in BNP testing.
      Effectiveness of this protocol was assessed by studying BNP utilization for 6
      month periods before and after institution of the protocol. Before: 1,886 assays
      in 752 patients; mean BNP assays per patient, 2.5; direct reagent cost, $33,948;
      1 BNP assay in 57.3% (431) of patients; 321 patients with multiple and 204
      patients with serial BNP requests. After: 782 assays (-58.5%) in 593 patients (
      21.1%); mean BNP assays per patient, 1.3 (-48.0%); direct reagent cost, $14,076 (
      58.5%); 1 BNP assay in 81.1% (481) of patients; 112 patients with multiple and 24
      patients with serial BNP requests (-88.2%). The emergency department was the
      source of BNP assays in 15.4% of requests before compared with 58.1% after
      introduction of the protocol. The protocol with slight modifications has been
      adopted by other VA medical centers in New England and may serve as a model for
      other medical facilities seeking to control BNP utilization.

PMID- 16891193
TI  - Impact of the cardiac troponin testing algorithm on excessive and inappropriate
      troponin test requests.
AB  - Cardiac troponin (cTn) is a key biomarker for the assessment of myocardial
      injury, but overutilization of this test has increased workload and costs. We
      developed and implemented an algorithm to eliminate excessive utilization.
      Significant reduction was observed after the implementation of the algorithm in
      total cTnI requests (29.9%; P = .007), requests from outpatient clinics (70.7%; P
      = .003), and other wards (42.8%; P = .003). Stat requests, the number of third
      requests, and more than 3 requests per patient were reduced significantly by
      42.8% (P = .004), 35.8% (P = .003), and 49.4% (P = .008), respectively. The test
      and labor costs each were reduced by 29.9% (P = .007 for each). There was no
      significant change in cTnI orders from emergency and critical care departments.
      The cTnI testing algorithm reduced unnecessary orders for cTnI tests with no
      reduction in meeting patients'critical needs. Reduction in unnecessary and
      inappropriate requests reduces labor and test costs.

PMID- 16891194
TI  - Reducing unnecessary inpatient laboratory testing in a teaching hospital.
AB  - After an inpatient phlebotomy-laboratory test request audit for 2 general
      inpatient wards identified 5 tests commonly ordered on a recurring basis, a
      multidisciplinary committee developed a proposal to minimize unnecessary
      phlebotomies and laboratory tests by reconfiguring the electronic order function
      to limit phlebotomy-laboratory test requests to occur singly or to recur within
      one 24-hour window. The proposal was implemented in June 2003. Comparison of
      fiscal year volume data from before (2002-2003) and after (2003-2004)
      implementation revealed 72,639 (12.0%) fewer inpatient tests, of which 41,765
      (57.5%) were related directly to decreases in the 5 tests frequently ordered on a
      recurring basis. Because the electronic order function changes did not completely
      eliminate unnecessary testing, we concluded that the decrease in inpatient
      testing represented a minimum amount of unnecessary inpatient laboratory tests.
      We also observed 17,207 (21.4%) fewer inpatient phlebotomies, a decrease
      sustained in fiscal year 20042005. Labor savings allowed us to redirect
      phlebotomists to our understaffed outpatient phlebotomy service.

PMID- 16891195
TI  - Analysis of search in an online clinical laboratory manual.
AB  - Online laboratory manuals have developed into an important gateway to the
      laboratory. Clinicians increasingly expect up-to-date laboratory test information
      to be readily available online. During the past decade, sophisticated Internet
      search technology has developed, permitting rapid and accurate retrieval of a
      wide variety of content. We studied the role of search in an online laboratory
      manual. We surveyed the utilization of search technology in publicly available
      online manuals and examined how users interact with the search feature of a
      laboratory handbook. We show how a laboratory can improve its online handbook
      through insights gained by collecting information about each user's activity. We
      also discuss future applications for search-related technologies and the
      potential role of the online laboratory manual as the primary laboratory
      information portal.

PMID- 16891196
TI  - Analysis of turnaround times in pathology: an approach using failure time
      analysis.
AB  - This article introduces the use of failure time analysis methods for studying
      turnaround times in pathology. The key to understanding the approach is to view a
      laboratory specimen like a living patient. When the specimen enters the
      laboratory, the time is analogous to the time of diagnosis for a patient. When
      the specimen's analysis is completed, the event is analogous to a patient who has
      died. To illustrate the approach, I use data previously published and data
      generated at the Durham, NC, Veterans Affairs Medical Center. I demonstrate that
      the Kaplan-Meier plotting method, the log-rank test, and the Cox model can all be
      applied to turnaround times and provide useful results.

PMID- 16891197
TI  - Composite recurrent hodgkin lymphoma and diffuse large B-cell lymphoma: one
      clone, two faces.
AB  - We describe a composite lymphoma with recurrent Hodgkin lymphoma and diffuse
      large B-cell lymphoma components manifesting as a single, perforated small
      intestinal tumor in a 56-year-old man with a history of classical Hodgkin
      lymphoma and recent relapse in the bone marrow. The resected mass had 2
      morphologically and immunophenotypically distinct components; 1 showed a
      pleomorphic cellular infiltrate with fibrosis and contained numerous, large
      Hodgkin/Reed-Sternberg-like cells and variants. The tumor cells were CD30+ and
      focally positive for CD15 but CD20-, CD79a-, and PAX-5-. In situ hybridization
      for Epstein-Barr virus (EBV) was strongly positive in the large pleomorphic tumor
      cells. The adjacent component displayed sheets of relatively uniform, large
      lymphoid cells with typical morphologic features of diffuse large cell lymphoma.
      The tumor cells showed uniform expression of tested B-cell antigens, absence of
      CD30 or CD15, and complete absence of EBV-encoded RNA. Separate molecular studies
      with immunoglobulin heavy and k light chain gene rearrangements clearly
      demonstrated an identical rearrangement pattern, indicating derivation from the
      same clone, which was confirmed by direct DNA sequencing analysis. Such
      distinctly different morphology, immunophenotype, and EBV status in different
      components within a clonally related single tumor mass is striking.

PMID- 16891198
TI  - Peripheral T-cell lymphoma with extensive dendritic cell network mimicking
      follicular dendritic cell tumor: a case report with pathologic, immunophenotypic,
      and molecular findings.
AB  - Peripheral T-cell lymphoma (PTCL) with a nodular pattern of growth is uncommon
      and may be misdiagnosed initially as a B-cell lymphoma or reactive process. We
      report a case of a rapidly growing PTCL with a distinctly nodular pattern in an
      axillary lymph node from an 89-year-old man. Immunohistochemical stains for CD21,
      CD23, and CD35 highlighted an extensive dendritic cell network that imparted the
      nodular appearance and, in addition, was associated intimately with the
      neoplastic cells. The neoplastic cells otherwise had an immunophenotype similar
      to previously reported cases of PTCL with a nodular pattern and germinal center
      origin (CD3+, CD4+, CD5+, bcl-6+, CD31+, subset CD10+, subset CXCL13+, and subset
      CD79a+). Molecular studies confirm a clonal T-cell receptor g gene rearrangement.
      This case emphasizes unusual morphologic features in a PTCL that may be mistaken
      for follicular lymphoma or a tumor of follicular dendritic cell origin.

PMID- 16891199
TI  - Expression of B cell-specific activator protein/PAX5 in acute myeloid leukemia
      with t(8;21)(q22;q22).
AB  - The blasts of acute myeloid leukemia (AML) with t(8;21)(q22;q22) frequently
      express the B-cell antigen CD19, which is regulated by B cell-specific activator
      protein (BSAP) encoded by the PAX5 gene, a protein important for B-cell lineage
      commitment and development. We assessed for BSAP expression in 28 AML cases with
      t(8;21) and 46 AML cases of other types. CD19 was expressed by 26 (93%) cases of
      AML with t(8;21) and 1 AML case (2%) without t(8;21). We also tested a subset of
      cases for the B-cell transcription factors Oct2 and OCA-B (BOB.1) and the B-cell
      antigens CD20, CD22, and CD79a. Immunostaining performed on bone marrow biopsy
      specimens demonstrated BSAP expression in all 28 AML cases with t(8;21): weak,
      21; strong, 7. By contrast, BSAP was expressed weakly in only 1 AML case without
      t(8;21). Oct2 was expressed strongly in 12 of 16 AML cases with t(8;21) and 19 of
      46 without t(8;21). OCA-B, CD20, CD22, or CD79a were negative in all cases
      assessed. These results indicate that silencing of PAX5 is not required for
      commitment to myeloid differentiation and that BSAP expression in AML is found
      mainly in cases with t(8;21).

PMID- 16891200
TI  - Quantitative evaluation of bone marrow angiogenesis in idiopathic myelofibrosis.
AB  - Bone marrow angiogenesis in patients with idiopathic myelofibrosis (IM) was
      evaluated by using a quantitative morphometric analysis test system. IM specimens
      had a significantly higher degree of bone marrow microvessel density (MVD)
      compared with control specimens. The higher degree of angiogenesis was associated
      with increased expression of basic fibroblast growth factor in megakaryocytes and
      endothelial cells in the IM bone marrow specimens. Increased vascular endothelial
      growth factor expression was seen in some cases of the prefibrotic form of IM.
      Morphometric quantitative measurements revealed that the MVD was reduced
      progressively in 4 cases of IM after allogeneic stem cell transplantation. These
      findings suggest that angiogenesis likely has an important role in the
      pathogenesis of IM.

PMID- 16891201
TI  - Effects of yeast on automated cell counting.
AB  - We studied the effects of yeast in peripheral blood samples on results reported
      by an ADVIA 120/2120 Hematology System (Bayer HealthCare, Diagnostics Division,
      Tarrytown, NY). In a simulated candidemia model, very high concentrations (1-5 x
      10(8) colony-forming units [CFU]/mL) of Candida glabrata and Candida parapsilosis
      caused a spuriously elevated platelet count. No such effect was observed with
      Candida albicans. All 3 yeast species, when present at a concentration of 1-5 x
      10(6) CFU/mL or greater, increased the automated WBC counts significantly and in
      a dose-dependent manner. The yeast cells were mainly misidentified as
      lymphocytes. All spurious results were flagged by the cell counter for
      microscopic review. We conclude that although the presence of yeast in a blood
      sample can interfere with the ADVIA 120/2120 Hematology System, compromised
      results are appropriately flagged by the instrument and are seen only when the
      yeast concentration is very high.

PMID- 16891202
TI  - Quantitative standards for fetal and neonatal autopsy.
AB  - Growth curves are essential for determining whether growth parameters lie within
      normal ranges. In the case of fetal and neonatal autopsy, relevant data are
      scattered across many publications, and few sources examine a large enough sample
      to be considered definitive. To ameliorate these inadequacies, regressions were
      created incorporating data from multiple sources both to increase accuracy and to
      condense available data into a single standard. When measurements were not well
      studied, the best available published standards are given. These regressions
      provide a valuable tool for clinicians who need to understand the significance of
      measurements obtained during autopsy.

PMID- 16891203
TI  - p14ARF, a prognostic predictor in HPV-negative vulvar carcinoma.
AB  - The present study addressed the impact of human papillomavirus (HPV), p14, and
      the product of the retinoblastoma gene (pRb) in vulvar carcinoma in relation to
      other clinicopathologic variables and prognosis. We immunohistochemically studied
      217 primary tumors from patients with vulvar carcinoma for the expression of pRb
      and p14. By the use of in situ hybridization, the primary tumors and 7 lymph node
      metastases were studied for the presence of HPV-16, HPV-18, HPV-31, and HPV-33
      DNA. HPV-infected cases significantly correlated with high expression of p14 (P <
      .01) and p16 (P < .01). In HPV- cases with high expression of p53, no p14
      expression predicted the poorest disease-specific survival (P < .01). For the
      first time, we have shown that p14 expression indicates longer disease-specific
      survival in patients with vulvar carcinoma. In patients with HPV- tumors
      expressing high levels of p53, low p14 indicated the poorest 5-year disease
      specific survival.

PMID- 16891204
TI  - Chromosome 17 abnormalities in pediatric neuroblastic tumor with abundant
      neuropil and true rosettes.
AB  - Although as a group, embryonal central nervous system tumors share a common
      background of primitive round cells, numerous distinctive histologic features
      allow for further subclassification. One tumor with a unique microscopic
      appearance is the recently described pediatric neuroblastic tumor with abundant
      neuropil and true rosettes (PNTANTR). We report 2 additional cases of this
      unusual tumor; both arose in 4-year-old children, one a midpontine tumor and the
      other a large cerebral lesion. The tumors contained hypercellular sheets of
      undifferentiated cells, broad zones of neuropil, and scattered perivascular,
      Homer Wright, and multilayered ependymoblastic-like rosettes. Isochromosome 17q
      was detected in multiple samples from one tumor, while the other tumor showed
      polysomy 17. No deletions of INI1 or amplifications of MYC or MYCN were detected.
      This report adds 2 cases to our experience of PNTANTR and is the first to
      demonstrate isochromosome 17q, a molecular alteration typical of
      medulloblastomas.

PMID- 16891205
TI  - Human papillomavirus and Epstein-Barr virus infection, p53 expression, and
      cellular proliferation in laryngeal carcinoma.
AB  - Laryngeal carcinomas are aggressive neoplasms with controversial association with
      the human papillomavirus (HPV) and Epstein-Barr virus (EBV). So far, the
      impairment of p53 protein function and its impact on cellular proliferation has
      not been studied adequately in these tumors. In this work, molecular biologic
      techniques were used to assess the frequency of HPV and EBV in 110 squamous cell
      carcinomas of the larynx. In addition, accumulation of p53 and Ki-67 cell
      proliferation antigen expression in malignant cells was assessed by
      immunohistochemical analysis. High-grade HPV was found in 37.3% of cases, and
      none had demonstrable EBV infection. Accumulation of p53 was found in 78.2% of
      the cases, and it was related to a high Ki-67 labeling index and higher
      histologic grade. The results demonstrate association of HPV with more than one
      third of laryngeal carcinomas studied, mainly glottic tumors. Tumors with
      increased cell proliferation were more frequently high grade, with p53
      accumulation and lymph node metastasis.

PMID- 16891206
TI  - An international telecytologic quiz on urinary cytology reveals educational
      deficits and absence of a commonly used classification system.
AB  - Urinary cytology is limited by high interobserver variability in the evaluation
      of cells with little atypia. We set up an online quiz on urinary cytology and
      tested the performance of 246 international participants. The quiz consisted of
      still images of 42 urinary specimens with equivocal morphologic features and 10
      control cases with an unequivocal cytologic diagnosis. The nature of the cells on
      the 292 quiz images had been verified by multitarget fluorescence in situ
      hybridization in addition to the information obtained by cystoscopy, clinical
      follow up, and/or histologic examination. The original quiz cases and the
      percentage of answers given by the participants can be viewed at:
      http://kathrin.unibas.ch/urinzyto/. High-grade cancers were diagnosed correctly
      in 76.0% and low-grade cancers in only 33.9%. Remarkably, 54.5% of all
      participants misclassified decoy cells as malignant. This study shows that large
      scale international online quizzes may be used to find educational deficits in
      cytopathology.

PMID- 16891207
TI  - Metastatic ductal adenocarcinoma of the prostate: cytologic features and clinical
      findings.
AB  - We retrospectively reviewed the cytologic features of metastatic prostatic ductal
      carcinoma (PDC) in 23 cases, clinical manifestations, and clinical outcomes.
      Cytologic smears typically showed tumor cells with abundant cytoplasm and oval
      nuclei arranged in papillary groups or flat and folded sheets, some of which
      showed peripheral nuclear palisading. However, these features could be focal,
      subtle, and even indistinguishable from those of acinar carcinoma, particularly
      when the ductal component was predominantly of a cribriform and solid pattern or
      coexisted with acinar carcinoma. A determination of a prostatic origin of a
      metastatic PDC, based on cytomorphologic features alone, could be difficult.
      Immunostaining for prostate-specific antigen and prostatic acid phosphatase
      proved helpful in determining a definitive diagnosis. The median followup of
      patients was 82 months, the median overall survival was 77 months, and the 5-year
      overall survival rate was 72%. Tumor growth pattern did not correlate with
      prognosis, but visceral metastasis conveyed a poor prognosis. The correlation
      with clinical and radiologic findings, a high index of suspicion, and the use of
      immunoperoxidase studies are important in making an accurate diagnosis.

PMID- 16891208
TI  - Lobular neoplasia in breast core needle biopsy specimens is associated with a low
      risk of ductal carcinoma in situ or invasive carcinoma on subsequent excision.
AB  - To address the significance of lobular neoplasia (LN) in breast core needle
      biopsy specimens, we prospectively obtained LN cases and correlated results of
      subsequent tissue sampling. LN was diagnosed by core needle biopsy in 467 women;
      in 101 (21.6%), invasive carcinoma (IC) or ductal carcinoma in situ (DCIS) was
      diagnosed concurrently. Two patients (0.4%) had previous diagnoses of IC or DCIS,
      and 17 (3.6%) had a concurrent diagnosis of contralateral IC or DCIS. Of 366
      patients without a concurrent diagnosis of IC or DCIS, subsequent tissue
      diagnoses were available for 156 cases (42.6%). Of 60 cases of LN and atypical
      ductal hyperplasia on the biopsy, 5 had IC and 10 had DCIS on the excision
      (total, 25%). Of 4 women with LN and a mucocele-like lesion on the biopsy, none
      had IC or DCIS on excision. Of 92 with LN alone on the biopsy, 7 had IC (6) or
      DCIS (1) on excision. Two cases were in sites away from the biopsy site, 3 in
      subsequent excisions of the biopsy site, and 2 after previous excision of the
      biopsy site without finding IC or DCIS. Although LN is associated with a high
      overall rate of IC and DCIS (30%), excision of the biopsy site for women with LN
      alone on core needle biopsy has a very low rate of IC and DCIS in our center.
      Women in whom biopsy sites are excised are still at risk for subsequent DCIS and
      IC.

PMID- 16891209
TI  - Absinthe--a review.
AB  - The alcoholic beverage absinthe is recently experiencing a revival after a
      yearlong prohibition. This review article provides information on all aspects of
      this bitter spirit and its major components, especially wormwood (Artemisia
      absinthium L.), which contains the toxic monoterpene thujone. Over 100 references
      on historic and current literature are provided. The topics comprise the history
      of the alcoholic drink starting from its invention in the eighteenth century.
      Historical and modern recipes are discussed in the context of different quality
      categories and possibilities to reduce the content of thujone are given. The
      analytical techniques used to verify compliance with the maximum limit of thujone
      as well as further possibilities for quality control of absinthe are discussed.
      The toxicology of absinthe is reviewed with regard to the cause of a syndrome
      called "absinthism," which was described after chronic abuse of the spirit in the
      nineteenth century. Finally, a food regulatory and food chemical evaluation is
      provided and minimum requirements for absinthe are suggested. Absinthe should
      have a recognizable wormwood flavor and after dilution with water the
      characteristic clouding should arise (louche-effect). Products, which are
      advertized as being of premium grade should be made by distillation, should have
      an alcoholic strength of at least 45%vol, and should not contain artificial dye.

PMID- 16891210
TI  - Current strategies for dairy waste management: a review.
AB  - Industrial waste management is nowadays one of the main issues for ensuring a
      sustainable environment. Dairy waste management in particular, is very crucial in
      view of the high organic matter and high nutrient levels contained in dairy
      effluents. Dairy waste can be effectively treated either with aerobic or
      anaerobic processes. The main advantages of the former consist of low yield, high
      kinetics, pathogen free product, and high temperature operation whereas the
      latter is a simple, low budget and conservative technology. Occasionally, pre
      treatment strategies (i.e. wetlands) are required in order to improve the
      efficiency of treatment methodology. Wetlands are a promising technology applied
      in order to remove the greater part of nutrients and minerals contained in milk
      based products.

PMID- 16891211
TI  - Importance of surface tension characterization for food, pharmaceutical and
      packaging products: a review.
AB  - This article reviews the various theoretical approaches that have been developed
      for determination of the surface tension of solids, and the applications to food
      industrial products. The surface tension of a solid is a characteristic of
      surface properties and interfacial interactions such as adsorption, wetting or
      adhesion. The knowledge of surface tension is thus of great interest for every
      domain involved in understanding these mechanisms, which recover a lot of
      industrial investigations. Indeed, it is the case for the packaging industry, the
      food materials science, the biomedical applications and the pharmaceutical
      products, cleaning, adhesive technology, painting, coating and more generally all
      fields in relation with wettability of their systems. There is however no direct
      method for measurements of surface tension of solids, except the contact angle
      measurements combined with an appropriate theoretical approach are indirect
      methods for estimation of surface tension of solids. Moreover, since the
      publication by Young (1805) who developed the basis of the theory of contact
      angle some two hundred years ago, measurements and interpretations are still
      discussed in scientific literature, pointing out the need to better understand
      the fundamental mechanisms of solid-liquid interfacial interactions. Applications
      of surface tension characterization in the field of food materials science are
      detailed, especially for packaging and coating applications, which recover
      different actual orientations in order to improve process and quality.

PMID- 16891212
TI  - Trends in postmortem aging in fish: understanding of proteolysis and
      disorganization of the myofibrillar structure.
AB  - Postmortem tenderization is caused by enzymatic degradation of key structural
      proteins in myofibrils as well as in extracellular matrix, and of proteins
      involved in intermyofibrillar linkages and linkages between myofibrils and the
      sarcolemma. The function of these proteins is to maintain the structural
      integrity of myofibrils. Current data indicate that calpains and cathepsins may
      be responsible for degradation of these proteins. Other phenomena occurring in
      cells postmortem (pH drop, sarcoplasmic Ca2+ increase, osmotic pressure rise,
      oxidative processes) may act in synergy with proteases. Our understanding of the
      underlying mechanisms of muscle degradation should be improved for an accurate
      evaluation of the postmortem muscle changes and consequently of the fish quality.

PMID- 16891213
TI  - Low oxygen and inert gas processing of foods.

PMID- 16891214
TI  - Circulating level of the platelet-derived CXC chemokine platelet factor 4 in
      chronic urticaria patients with or without coexistent euthyroid Hashimoto's
      thyroiditis.
AB  - The concept of autoimmune aetiology of some cases of chronic urticaria (CU) has
      been supported by several observation including wheal-and-flare reaction induced
      by intradermal injection of autologous serum as well as association with other
      autoimmune diseases, in particular Hashimoto's thyroiditis (HT). It is known that
      activated platelets may actively participate in immune-inflammatory processes.
      Therefore, we assessed whether autoimmune phenomenon associated with CU influence
      the systemic platelet activity measured by circulating level of platelet factor 4
      (PF-4). Plasma level of PF-4 was analysed using enzyme-linked immunosorbent assay
      in twelve women with strong positive response to autologous serum skin test
      (ASST) suffering from CU, twelve female patients with strong positive ASST
      suffering from both CU and untreated, HT as well as sixteen healthy women. All
      the subjects were clinically and biochemically euthyroid. There were no
      statistically significant differences between the CU patients with or without
      euthyroid HT and plasma PF-4 level in healthy controls. In patients with both CU
      and thyroiditis, plasma level of PF-4 did not correlate significantly with the
      level of antibodies against thyroperoxidase. It seems that circulating level of
      the platelet-derived chemokine is not increased in CU patients with positive
      response to ASST, regardless the occurrence of euthyroid HT.

PMID- 16891215
TI  - Transforming growth factor-beta: an important role in CD4+CD25+ regulatory T
      cells and immune tolerance.
AB  - The transforming growth factor-beta (TGF-beta) protein family is highly
      evolutionarily conserved and they have been implicated in many biological
      processes. Also, TGF-beta can exert pivotal functions in the immune system. It is
      widely accepted that regulatory T cells (Treg cells) play an important role in
      the maintenance of the immune homeostasis, but the underlying molecular
      mechanisms through which they can gain and/or perform suppressive functions in an
      active way remains to be defined. Though the engagement of TGF-beta in the Treg
      cells has been discounted for a period of time, an emerging body of data has
      established a close link between Treg cells and TGF-beta, as TGF-beta has been
      demonstrated to induce the expression of Foxp3, which acts as a master regulator
      for the development and function of Treg cells. We will, herein, focus on the
      crucial role of TGF-beta signaling in Treg cell biology and summarize the current
      studies regarding TGF-beta in the generation and function of CD4+CD25+Treg cells
      both in vivo and in vitro.

PMID- 16891216
TI  - Subtle differences in HLA DQ haplotype-associated presentation of AChR alpha
      chain peptides may suffice to mediate myasthenia gravis.
AB  - The HLA DQA1 and DQB1 alleles were determined on a set of 24 myasthenia gravis
      patients that had previously been examined for their T-cell proliferative
      responses to the 18 overlapping peptides representing the extracellular domain of
      hAChR alpha-chain. Patient responses according to assumed cis or trans haplotypes
      were significantly higher in most cases relative to normal controls. Comparisons
      of in vitro peptide-stimulated T-cell responses of patient pairs which had
      DQA1:DQB1 in common displayed responses in tighter distribution relative to
      comparisons in which patient pairs did not share the same DQA1:DQB1 haplotype.
      Similar haplotypes, such as DQA1*0102:DQB1*0602 and DQA1*0102:DQB1*0604, tended
      to exhibit similar responses and were grouped according to this similarity.
      Modified F-test and Student's T-test analyses on DQ isoform bearing groups
      revealed that high responses to peptide alpha34-49 were associated with
      A1*0102:B1*0602/0604, A1*0301:B1*0302 and A1*0401/0303:B1*0301. Peptide alpha146
      162 showed higher responses in A1*0301:B1*0302 group and moderate responses in
      A1*0401/0303:B1*0301 groups. Differences in the age of disease onset relative to
      DQ haplotypes were also observed. Groups of A1*0301:B1*0302, A1*0501:B1*0201 and
      A1*0102:B1*0604 showed earlier ages of disease onset relative to those of
      A1*0102:B1*0602 or A1*0505:B1*0301.

PMID- 16891217
TI  - Upregulation of CD4+CD25+ T lymphocyte by adenovirus-mediated gene transfer of
      CTLA4Ig fusion protein in experimental autoimmune myocarditis.
AB  - OBJECTIVE: To explore the effects of adenovirus vector-mediated gene transfer of
      CTLA4Ig fusion protein on CD4+CD25+ T cells in experimental autoimmune
      myocarditis (EAM). METHODS: EAM was induced by porcine cardiac myosin as
      previously described. Adenovirus vector-mediated CTLA4Ig gene was administrated
      intravenously in EAM rats on days 1, 4 and 7, with EGFP as control. On day 21,
      myocardium histopathology was examined and CD4+CD25+ T cells were isolated.
      Proliferation and suppression assays were used to evaluate the suppressive
      capacity of CD4+CD25+ T cells in vitro. Relative mRNA level of Foxp3 and TGF-beta
      was determined by quantitative real-time RT-PCR; expression of CTLA-4, B7-1 and
      B7-2 protein was compared with Western blot in CD4+CD25+ Tregs. RESULTS: Severe
      inflammatory lesions were observed in the hearts of EGFP-treated EAM rats and the
      untreated ones, while Ad-CMV-CTLA4Ig alleviated the myocarditis histologically.
      Adenovirus vector-mediated CTLA4Ig gene transfer up-regulated the proportion of
      CD4+CD25+ Tregs significantly. T cell proliferation was greatly inhibited in the
      CTLA4Ig group compared with the untreated and EGFP-treated groups in vitro. CTLA
      4 and B7-2 proteins were down-regulated in the CTLA4Ig group, Foxp3 and TGF-beta
      mRNA was up-regulated significantly by CTLA4Ig treatment. CONCLUSIONS: Adenovirus
      vector-mediated CTLA4Ig gene transfer alleviated inflammation in EAM, one of the
      potential mechanisms is up-regulation of CD4+CD25+ Tregs.

PMID- 16891218
TI  - Bacterial extract (OM-89) specific and non specific immunomodulation in
      rheumatoid arthritis patients.
AB  - The Escherichia Coli bacterial extract (OM-89) is used in the treatment of
      rheumatoid arthritis (RA). We evaluated the immunological changes induced by oral
      administration of OM-89 in 12 RA patients (polyclonal T cell reactivity to PHA, T
      cell precursor frequencies specific for OM-89 and Tetanus toxoid (TT), a control
      antigen and the release of Th1 (IFN-gamma, TNF-alpha), Th2 (IL-4) and T
      regulatory 1 cell (Tr1) (IL-10) cytokines in the supernatants of PBMC cultures.
      Stimulation index in response to PHA decreased at month 3 as well as T cell
      precursor frequencies specific for TT with similar trends for OM-89-specific T
      cell precursor frequencies. OM-89 induced a strong production of IL-10, a
      significant decrease in IL-4 production while TNF-alpha and IFN-gamma production
      tended to decrease during the study. Our results suggest that OM-89 has
      immunomodulatory properties by inducing changes in PBMC cytokines release
      suggestive of an induced Tr1 response to OM-89.

PMID- 16891219
TI  - The expression of collagenase 3 (MMP-13) mRNA in the synovial tissue is
      associated with histopathologic type II synovitis in rheumatoid arthritis.
AB  - The histopathologic analysis of the synovial tissue is important to distinguish
      rheumatoid arthritis (RA) from other forms of synovitis and to provide
      information about prognosis and therapeutic strategies at early stages of the
      disease. In this context, the present study was performed to investigate the
      correlation between immunohistopathological and morphological features of
      synovitis and the expression of collagenase 3 (MMP-13) known to contribute
      significantly to cartilage degradation in RA. In the histopathologic scoring
      system used in this study, type I synovitis is characterized by B lymphocyte
      infiltration and an intact lining, and is only mild destructive to cartilage and
      bone. Type II shows marked diffuse infiltrations of macrophages and T
      lymphocytes, an ulcerated lining, fibrin exudation, and invasive growth into
      cartilage and bone tissue. Investigating 36 patients with RA, 21 patients (58%)
      were positive for the expression of collagenase 3 mRNA in the synovial tissue.
      Among these patients, 19 showed a histopathologic type II synovitis and only 2
      patients had undifferentiated synovitis. In contrast, synovial tissue samples
      from patients without collagenase 3 mRNA expression were characterized in 6 cases
      by type I, in 5 cases by type II and in 4 cases by undifferentiated synovitis.
      The analysis of the clinical data revealed that RA patients with a
      histopathologic type II synovitis and synovial tissue collagenase 3 mRNA
      expression had elevated levels of systemic markers of inflammation and received
      stronger therapies. The data suggest, that collagenase 3 expression and the
      histopathologic type II synovitis are associated with a severe and destructive
      course of RA.

PMID- 16891220
TI  - Different islet protein expression profiles during spontaneous diabetes
      development vs. allograft rejection in BB-DP rats.
AB  - Type 1 diabetes (T1D) is characterized by selective autoimmune destruction of the
      insulin producing beta-cells in the islets of Langerhans. When the beta-cells are
      destroyed exogenous administration of insulin is necessary for maintenance of
      glucose homeostasis. Allogeneic islet transplantation has been used as a means to
      circumvent the need for insulin administration and has in some cases been able to
      restore endogenous insulin production for years. However, long life
      immunosuppression is needed to prevent the graft from being rejected and
      destroyed. Changes in protein expression pattern during spontaneous diabetes
      development in the diabetes prone BioBreeding rat (BB-DP) have previously been
      described. In the present study, we have investigated if any of the changes seen
      in the protein expression pattern during spontaneous diabetes development are
      also present during allograft rejection of BB-DP rat islets. Two hundred neonatal
      islets were syngeneically transplanted under the kidney capsule of 30 day old BB
      DP rats and removed prior to and at onset of diabetes. Allogeneically
      transplanted islets from BB-DP rats were removed before onset of allograft
      rejection and at maximal islet graft inflammation (rejection). The protein
      expression profiles of the transplants were visualised by two-dimensional gel (2
      DG) electrophoresis, analysed and compared. In total, 2590 protein spots were
      visualised and of these 310 changed expression (p < 0.01) in syngeneic islet
      transplants in the BB-DP rats from 7 days after transplantation until onset of
      diabetes. In BB-DP islets transplanted to WK rats 53 protein spots (p < 0.01)
      showed changes in expression when comparing islet grafts removed 7 days after
      transplantation with islet grafts removed 12 days after transplantation where
      mononuclear cell infiltration is at its maximum. Only four protein spots (1%)
      were significantly changed in both syngeneic (autoimmune) and allogeneic islet
      destruction. When comparing protein expression changes in syngeneic BB-DP islet
      transplants from 37 days after transplantation to onset of diabetes with protein
      expression changes in allografts from day 7 to 12 after transplantation only
      three spot were found to commonly change expression in both situations. In
      conclusion, a large number of protein expression changes were detected in both
      autoimmune islet destruction and allogeneic islet rejection, only two overlaps
      were detected, suggesting that autoimmune islet destruction and allogeneic islet
      rejection may result from different target cell responses to signals induced by
      the cellular infiltrate. Whether this reflects activation of distinct signalling
      pathways in islet cells is currently unknown and need to be further investigated.

PMID- 16891221
TI  - Characterization of anti-islet cytotoxic human T-cell clones from patients with
      type 1 diabetes mellitus.
AB  - To identify important anti-islet T-cells and their target antigen(s), we have
      isolated and characterized seventeen human T-cell clones which are reactive to an
      extract of rat insulinoma (RIN) cells from three children with new onset type 1
      diabetes mellitus (T1D). Of these 17 clones, 15 were found tissue specific. Six
      of eight tested tissue specific clones did not recognize known islet antigens
      such as GAD, 52 kDa islet protein, insulin, ICA512, and heat shock protein 60
      (hsp60), suggesting that these clones recognize an autoantigen not previously
      identified. All tested clones were phenotypically CD4 and functionally Th0 or
      Th0/Th1 cells. One RIN extract reactive clone (2E9) recognized hsp60 and was CD4
      and TCR alpha/beta positive. This clone also proliferated in response to human
      and rat islets suggesting that the antigen is conserved between species. This
      clone and 75% of all the tested RIN reactive clones exhibited anti-islet
      cytotoxicity by lysing target cells coated with RIN extract. HLA DR determinants
      may play a role in this cytotoxic activity since preincubation with HLA DR
      antibody decreased the anti-islet cytoxicity of the two tested clones. In
      conclusion, we have isolated RIN reactive CD4+T-cell clones from diabetic
      subjects, six of which appears tissue specific and non-reactive to putative
      important islet antigens, and in turn may be recognizing yet undiscovered islet
      antigens. The high frequency anti-islet cytotoxic properties of the islet
      reactive clones provides evidence for a role of CD4+ cytotoxic T-lymphocytes in
      the diabetic process. Further, the isolation of hsp60 reactive clone with anti
      islet cytotoxic properties suggests that cell mediated immunity against hsp60 may
      be important in the pathogenesis of diabetes.

PMID- 16891225
TI  - President's Page.

PMID- 16891222
TI  - Effect of standard nicotinamide in the prevention of type 1 diabetes in first
      degree relatives of persons with type 1 diabetes.
AB  - BACKGROUND: Nicotinamide has been used with success to prevent type 1 diabetes in
      animal models and humans. This vitamin B3 derivative has attracting effects on
      beta-cell protection and regeneration. AIM/HYPOTHESIS: To evaluate the effect of
      standard nicotinamide administration on type 1 diabetes prevention in first
      degree relatives of persons with type 1 diabetes as well as on the concentrations
      of islet-cell-related autoantibodies, insulin secretion and peripheral
      sensitivity. SUBJECTS AND METHODS: A randomized double-blind placebo controlled
      intervention trial was conducted in 40 first degree relatives of type 1 diabetic
      patients. Persistence of ICA ( >or= 10 JDF units) was among inclusion criteria.
      Participants were randomly allocated oral standard nicotinamide (1.2 g/m2) or
      placebo for 5 years. Groups were also stratified by age. Islet associated
      antibodies, fasting blood glucose, fasting plasma insulin concentrations, OGTT,
      IVGTT and HLA-DR genotyping were performed in all participants. The main
      criterion to stop treatment was type 1 diabetes development as defined by WHO.
      RESULTS: Type 1 diabetes development frequencies were similar between the
      treatment groups. ICA frequencies at the end of the study, first phase insulin
      release, and insulin sensitivity did not differ between groups as well. None of
      the participants suffered from any adverse events described for nicotinamide.
      CONCLUSIONS: Type 1 diabetes prevention trial using standard nicotinamide is
      feasible but fails to prevent or delay the disease onset at the dose we used.

PMID- 16891223
TI  - Frequency and significance of antibodies to cyclic citrullinated peptide in type
      1 autoimmune hepatitis.
AB  - OBJECTIVES: Determine the frequency, clinical phenotype, and prognostic
      implications of antibodies against cyclic citrullinated peptides in patients with
      type 1 autoimmune hepatitis. METHODS: Three hundred and ninety-five serum samples
      from 179 patients were tested by enzyme-linked immunosorbent assay, and findings
      correlated with clinical and histological features, frequency of HLA DR3 and DR4,
      and treatment outcome. RESULTS: Twenty patients (11%) had antibodies against
      cyclic citrullinated peptides. Seropositivity was associated with a higher
      frequency of rheumatoid arthritis (RA) (25 vs. 0%, P < 0.001). Patients with
      antibodies against cyclic citrullinated peptides also had a significantly greater
      occurrence of histological cirrhosis at presentation (47 vs. 20%, P = 0.01) and
      death from hepatic failure than seronegative patients (25 vs. 9%, P = 0.04).
      Cirrhosis at presentation occurred more commonly in the patients with antibodies
      against cyclic citrullinated peptides and RA than in the other patients (100 vs.
      21%, P = 0.005). CONCLUSIONS: Antibodies against cyclic citrullinated peptides
      occur in a subgroup of patients with type 1 autoimmune hepatitis who have a
      greater occurrence of cirrhosis at presentation and death from hepatic failure.
      Their presence with RA at accession characterizes a subgroup with cirrhosis.

PMID- 16891226
TI  - Letter from the Editor-in-Chief.

PMID- 16891227
TI  - Reperfused myocardial infarction in mice: 3D mapping of late gadolinium
      enhancement and strain.
AB  - We developed mathematical modeling tools for mapping 3D infarct geometry from
      multislice late gadolinium enhancement data, allowing fusion with multislice MR
      tagging data, in mice with myocardial infarction. Five C57BL/6 mice were imaged
      at baseline, 1, 7 and 28 days after 60 min occlusion of the left anterior
      descending coronary artery. The 3D infarct geometry was mapped in material
      coordinates, and registered with 3D strain, showing permanent dysfunction in
      infarcted segments, intermediate function in the adjacent zone, and maintained
      function in the remote zone. 3D mapping of late enhancement and strain allows
      registration of multiple studies in a consistent framework.

PMID- 16891228
TI  - How to perform an accurate assessment of cardiac function in mice using high
      resolution magnetic resonance imaging.
AB  - High-resolution magnetic resonance cine imaging (cine-MRI) is a method that
      allows for a non-invasive assessment of left ventricular function and mass. To
      perform this quantitation, hearts are imaged from the base to the apex by a stack
      of two-dimensional images. Thus, analysis of myocardial mass and function by cine
      MRI does not rely on geometric assumptions. Geometric and functional parameters,
      such as end-diastolic volume (EDV), end-systolic volume (ESV) or ejection
      fraction (EF), are obtained by subsequent image segmentation of the respective
      cine frames in each slice. While this technique has been well established in
      clinical practice, it is now rapidly becoming the reference method in
      experimental cardiovascular MRI for accurate quantification of cardiac
      parameters, thereby aiding the phenotyping of the increasing number of transgenic
      and surgical mouse models. However, accurate measurement of cardiac functional
      parameters requires the images to be acquired in short-axis orientation of the
      heart, which can be difficult to define, particularly in animals with diseased
      hearts. Furthermore, data analysis can be the source of a systematic error,
      mainly for myocardial mass measurement. Here, we describe a protocol that allows
      for a quick and reproducible approach of obtaining the relevant cardiac views for
      cine-MRI, and we explain how an accurate experimental image analysis can be
      performed.

PMID- 16891229
TI  - Coronary artery magnetic resonance angiography (MRA): a comparison between the
      whole-heart and volume-targeted methods using a T2-prepared SSFP sequence.
AB  - In this study, coronary MRA was performed on 10 healthy volunteers using the
      whole-heart and volume-targeted scans with comparable imaging parameters. Similar
      results in the SNR, CNR, and vessel diameter were observed. The depicted length
      of coronary arteries was longer using the whole-heart scan (whole-heart: RCA/LAD
      = 13.4 +/- 3.9/10.5 +/- 1.6 cm; volume-targeted: RCA/LAD = 11.0 +/- 2.6/8.7 +/-
      1.8 cm). Imaging times for the RCA- (3.8 +/- 1.4 minutes) and LAD-targeted (3.6
      +/- 1.3 minutes) are similar, while the time required for one whole-heart scan is
      significantly longer (12.2 +/- 4.0 minutes). The measured vessel sharpness was
      higher using the volume-targeted method (whole-heart: RCA/LAD = 0.65 +/-
      0.18/0.78 +/- 0.16; volume-targeted: RCA/LAD = 0.84 +/- 0.22/0.90 +/- 0.20).
      Combination of the whole-heart and volume-targeted methods could be potentially
      useful in clinical applications of coronary MRA.

PMID- 16891230
TI  - Cardiac cine MR-imaging at 3T: FLASH vs SSFP.
AB  - The implications of an increase in field strength, from 1.5 T to 3 T, for routine
      functional cardiac examinations have been systematically investigated. Flip angle
      optimization was carried out for identical SSFP and FLASH cine imaging sequences
      at 1.5 T and 3 T, which supported the use of 20 degrees (FLASH 1.5 T and 3 T) and
      >60 degrees (SSFP 1.5 T and 3 T). The optimized sequences were applied in a study
      of cardiac function in a group of ten normal volunteers. Both SSFP and FLASH
      sequences showed significant SNR increases in the myocardium and blood at 3 T
      compared with 1.5 T, increases of 48% and 30% (myocardium and blood,
      respectively) for the SSFP sequence and 19% and 13% for the FLASH sequence. The
      SSFP sequence also showed a significant increase in CNR (22%). Image quality
      assessment revealed that the SSFP acquisitions were superior to FLASH at both
      field strengths. Although SSFP contained more artifacts at 3 T, they would not
      prevent its clinical use. We conclude that cardiac functional examinations at 3 T
      should use SSFP sequences.

PMID- 16891231
TI  - Mean-average wall shear stress measurements in the common carotid artery.
AB  - In this study we determined mean-average wall shear stress values in the common
      carotid artery and assessed if there is a difference in mean-average WSS between:
      1) patients with bilateral carotid bifurcation disease and 2) similar-aged
      volunteers with no evidence of disease. Sixteen patients with bilateral disease
      of the carotid bifurcation, and 8 volunteers were included in the study. Magnetic
      resonance phase velocity mapping was used to determine velocity, flow, vessel
      cross-sectional dimensions, and mean-average WSS in the common carotid artery in
      both the patients and volunteers. Mean-average WSS in the common carotid artery
      was 7.5 +/- 2.5 dynes/cm2 in patients and 8.0 +/- 4.1 dynes/cm2 in volunteers.
      There was no significant difference in mean-average WSS, average velocity, peak
      velocity, flowrate, or vessel diameter in the common carotid artery between
      patients and volunteers.

PMID- 16891232
TI  - Primary myocardial dysfunction in autosomal dominant EDMD. A tissue doppler and
      cardiovascular magnetic resonance study.
AB  - BACKGROUND: Emery-Dreifuss muscular dystrophy is a genetically heterogeneous form
      of muscular dystrophy. One form is inherited in an X-linked fashion and is
      secondary to mutations in the gene encoding the nuclear protein emerin. A more
      common variant is inherited in an autosomal dominant way (EDMD2) due to mutations
      affecting the nuclear lamina protein lamin A/C. Typical features of both
      conditions are relatively mild skeletal muscle weakness, but cardiac involvement
      develops almost invariably by adult age, including conduction defects,
      arrhythmias and cardiomyopathy. Thus, early detection of cardiac abnormalities
      may be important for planning early therapeutic intervention. AIM: In this study,
      we hypothesized that early myocardial dysfunction can be detected by tissue
      Doppler echocardiography and CMR in unselected patients with the autosomal
      dominant form of Emery-Dreifuss muscular dystrophy. This would suggest that
      fibrosis could be implicated in the pathogenesis of cardiac dysfunction in EDMD2.
      METHODS: Eight consecutive patients with genetically proven EDMD2 without
      pacemakers were enrolled in the study and compared to eight age-matched controls.
      All patients and controls first underwent a comprehensive echocardiographic
      Doppler examination, followed by measurement of mitral annular velocities using
      pulsed tissue Doppler. Color M-mode tissue images were recorded from the
      parasternal long axis projections to derive Myocardial Velocity Gradients (MVG).
      Subsequently, all subjects underwent cardiovascular magnetic resonance (CMR)
      imaging for function, intrinsic myocardial tissue contrast using T1 and T2
      weighted spin echo (TSE) for fat deposition and extrinsic contrast (Gadolinium
      DTPA late fibrosis imaging). Strain measurements, using harmonic phase imaging
      (HARP) tagging were also derived. RESULTS: Cavity dimensions LV mass and
      fractional shortening were similar between patients and controls. The overall
      body mass index was less in patients than in controls (14.5 +/- 1.4 vs. 18.1 +/-
      2.4 g/m2, p < 0.002). While systolic MVG were similar between groups, the early
      diastolic MVG was lower in patients than in controls (4 +/- 1.2 s-1 vs. 7.1 +/-
      2.7, p < 0.02). On CMR, LA and LV, RV volumes were similar between patients and
      controls. CMR strain patterns, however, showed a significant reduction in
      inferior wall contractility in patients compared to controls (-0.06 +/- 0.02 vs 
      0.09 +/- 0.03, p < 0.05). No patient showed late gadolinium enhancement.
      CONCLUSION: Patients with EDMD2 have abnormal left ventricular function prior to
      developing any cardiac symptoms. The absence of myocardial fibrosis, however, by
      CMR suggests that this functional abnormality may not be secondary to scarring
      but could precede it. Tissue Doppler echocardiography and CMR are sensitive
      methods of assessing the presence of myocardial dysfunction prior to the
      development of any cardiovascular symptoms.

PMID- 16891233
TI  - Comparison of the detection of subtle changes in myocardial regional systolic
      function using qualitative and semi-quantitative techniques.
AB  - PURPOSE: To evaluate qualitative wall motion assessment vs. quantitative wall
      thickening for the assessment of subtle changes in myocardial systolic function
      using cine MRI. METHODS: Cine MR images were obtained in 5 canines with a
      significant coronary artery stenosis and in 2 controls on a 1.5T scanner.
      Qualitative results were obtained using a numerical scoring system; quantitative
      analysis was performed using a semi-automatic segmentation program. The
      techniques were matched and compared using Spearman correlations. RESULTS: All
      correlations in the experimental group revealed significant but weak to moderate
      relationships between the qualitative and quantitative results (e.g., at-risk
      tissue rho = 0.363, p < 0.0001; remote tissue rho = 0.275, p = 0.0002), with each
      identifying changes in regional function that ensued following creation of the
      stenosis. Intra-observer variability was reasonable in both methods when repeat
      analysis on a subset of the data was performed, with both techniques showing a
      significant correlation between the repeated measurements (quantitative - rho =
      0.52, p < 0.0001; qualitative - rho = 0.54, p < 0.0001). CONCLUSION: Both methods
      were able to detect very limited wall motion abnormalities present in the canines
      with significant stenosis and either method gives comparable results.

PMID- 16891234
TI  - Left ventricular outflow tract planimetry by cardiovascular magnetic resonance
      differentiates obstructive from non-obstructive hypertrophic cardiomyopathy.
AB  - The relation to the pressure gradient as assessed by echocardiography and the CMR
      derived planimetry of the LVOT is not known, no values for the differentiation of
      obstruction exist. We studied 37 patients with hypertrophic cardiomyopathy and 14
      healthy controls using standard sequences with 3D coverage of the left
      ventricular outflow tract. A cutoff value of 2.7 cm2 identified obstruction as
      defined by echocardiography with 100% accuracy. CMR planimetry at rest is a
      promising tool to evaluate patients with hypertrophic cardiomyopathy.

PMID- 16891235
TI  - Diagnosis of congenital obstructive aortic arch anomalies in Chinese children by
      contrast-enhanced magnetic resonance angiography.
AB  - OBJECTIVE: The purpose of this study was to evaluate the accuracy of contrast
      enhanced magnetic resonance angiography for the diagnosis of congenital
      obstructive aortic arch anomalies in children and compare it with transthoracic
      echocardiography and other MR imaging techniques (ECG gated T1-weighted spin-echo
      imaging and gradient-echo cine imaging). MATERIALS AND METHODS: Contrast-enhanced
      magnetic resonance angiography, ECG gated T1-weighted spin-echo imaging, and
      gradient-echo cine imaging were performed for the diagnosis of congenital
      obstructive aortic arch anomalies in 416 patients from April 1999 to March 2005
      (age range, 3 days to 12 years; mean age, 2.4 years) using a GE 1.5T MR scanner.
      Transthoracic echocardiography was performed in all patients prior to MR
      examination. Surgery and/or conventional X-ray angiocardiography were done in all
      patients to determine the final diagnosis. RESULTS: The population consisted of
      416 patients. Congenital obstructive aortic arch anomalies were diagnosed in 213
      patients and ruled out in 203 patients by operation and/or conventional X-ray
      angiocardiography. Among the 213 patients with anomalies, coarctation of aorta
      was diagnosed in 174, interruption of aortic arch was diagnosed in 35, and
      persistent fifth aortic arch with fourth aortic arch interruption was diagnosed
      in 4 patients. Among the 35 patients with interruption of aortic arch, 21 were of
      type A, and 14 were of type B. The diagnostic sensitivity, specificity and
      accuracy of contrast-enhanced magnetic resonance angiography for congenital
      obstructive aortic arch anomalies were 98% (208/213), 99% (201/203) and 98%
      (409/416), respectively. The diagnostic sensitivity, specificity and accuracy of
      transthoracic echocardiography were 88% (187/213), 92% (186/203) and 90%
      (373/416), respectively. The diagnostic sensitivity, specificity and accuracy of
      other MR imaging techniques (ECG gated T1-weighted spin-echo imaging and gradient
      echo cine imaging) were 89% (189/213), 84% (170/203) and 86% (359/416),
      respectively. CONCLUSION: Contrast-enhanced magnetic resonance angiography is a
      reliable, noninvasive imaging technique for the diagnosis of congenital
      obstructive aortic arch anomalies in children. Occasionally, even more
      information can be obtained from this technique than from conventional X-ray
      angiocardiography. Contrast-enhanced magnetic resonance angiography is superior
      to transthoracic echocardiography and other MR imaging techniques (ECG gated T1
      weighted spin-echo imaging and gradient-echo cine imaging) for diagnosis of
      congenital obstructive aortic arch anomalies in children.

PMID- 16891236
TI  - Anatomical and functional evaluation of myocardial bridging on the left anterior
      descending artery by cardiovascular magnetic resonance imaging.
AB  - A myocardial muscle bridge spans a segment of a major epicardial coronary artery
      that is located in the myocardium. This anatomic configuration can be responsible
      for angina pectoris, arrhythmias or even death. The current reference standard
      for diagnosis is conventional x-ray coronary angiography showing systolic
      compression of an epicardial vessel and the typical angiographic "milking
      effect." We report the case of a patient with myocardial bridging on the left
      anterior descending artery, in whom a combination of noninvasive high resolution
      display of the coronary artery lumen, visualization of the myocardium and
      functional assessment of blood flow during dobutamine stimulation by
      cardiovascular magnetic resonance imaging was performed.

PMID- 16891237
TI  - 2D-spatially-selective real-time magnetic resonance imaging for the assessment of
      microvascular function and its relation to the cardiovascular risk profile.
AB  - BACKGROUND: While local endothelial dysfunction of conduit arteries is well
      recognized as an early step in atherogenesis, contradictory observations are
      reported with regard to alterations in the microcirculation and their association
      with cardiovascular risk factors (RFs). A real-time MR approach was developed to
      investigate the relationship between the RFs profile and microcirculatory
      alterations assessed as impairment of reactive hyperemic flow in the leg
      circulation. METHODS: The MR technique was applied to patients (n = 17, Pats1)
      with 1.8 +/- 0.8 RFs but without peripheral arterial occlusive disease (PAD), to
      age-matched healthy controls (n = 13, Con1), to young controls (n = 12, 23 +/- 4
      y), and to patients with RFs and PAD (n = 8, Pats2). RESULTS: Superficial femoral
      artery (SFA) peak hyperemic flow in Pats1 was reduced vs Con1 (24.6 +/- 4.2 vs
      30.4 +/- 7.3 mL min-1 100 mL-1 calf tissue, p < 0.02), and minimal vascular
      resistance increased incrementally with the number of RFs and with Framingham and
      Procam risk scores. Flow-mediated vasodilation (FMD) of the SFA was blunted in
      both Pats1 and Con1 (-0.5 +/- 3.4% and +0.6 +/- 3.2%, respectively, both ns vs
      0). In young controls, peak hyperemic flow (30.1 +/- 3.3 mL min-1. 100 mL-1) and
      endothelium-independent vasodilation (9.2 +/- 10.0%) were preserved, while FMD
      was minimal (2.0 +/- 5.9%,p < 0.02 vs endothelium-independent vasodilation). In
      Pats2, peak hyperemic flow was severely reduced (12.2 +/- 3.6 mL min-1 100 mL-1,
      p < 0.0003 vs Con1 and Pats1), and both FMD and endothelium-independent
      vasodilation were absent. CONCLUSIONS: Reactive hyperemic flow in the SFA,
      reflecting microcirculatory function of the lower limb, gradually decreases with
      increasing cardiovascular risk suggesting a role for microvascular dysfunction in
      atherogenesis. The presented MR approach might become a valuable tool to study
      (micro)-vascular pathophysiology.

PMID- 16891239
TI  - Changes in tumour oxygenation during fractionated hyperthermia and radiation
      therapy in spontaneous canine sarcomas.
AB  - Tumour oxygenation was measured in seven canine soft tissue sarcomas being
      treated with a fractionated course of radiation and hyperthermia. Measurements
      obtained during treatment were compared to pre-treatment measurements. The most
      important finding was an increase in oxygenation in tumours with low pre
      treatment oxygenation that persisted throughout treatment. This is an
      advantageous hyperthermia effect as it may lead to increased radiation cell
      killing at each fraction. In other tumours, potentially less advantageous changes
      in oxygenation may be hyperthermia fractionation related and this deserves
      further investigation.

PMID- 16891240
TI  - Prospective treatment planning to improve locoregional hyperthermia for
      oesophageal cancer.
AB  - BACKGROUND: In the Academic Medical Center (AMC) Amsterdam, locoregional
      hyperthermia for oesophageal tumours is applied using the 70 MHz AMC-4 phased
      array system. Due to the occurrence of treatment-limiting hot spots in normal
      tissue and systemic stress at high power, the thermal dose achieved in the tumour
      can be sub-optimal. The large number of degrees of freedom of the heating device,
      i.e. the amplitudes and phases of the antennae, makes it difficult to avoid
      treatment-limiting hot spots by intuitive amplitude/phase steering. AIM:
      Prospective hyperthermia treatment planning combined with high resolution
      temperature-based optimization was applied to improve hyperthermia treatment of
      patients with oesophageal cancer. METHODS: All hyperthermia treatments were
      performed with 'standard' clinical settings. Temperatures were measured
      systemically, at the location of the tumour and near the spinal cord, which is an
      organ at risk. For 16 patients numerically optimized settings were obtained from
      treatment planning with temperature-based optimization. Steady state tumour
      temperatures were maximized, subject to constraints to normal tissue
      temperatures. At the start of 48 hyperthermia treatments in these 16 patients
      temperature rise (DeltaT) measurements were performed by applying a short power
      pulse with the numerically optimized amplitude/phase settings, with the clinical
      settings and with mixed settings, i.e. numerically optimized amplitudes combined
      with clinical phases. The heating efficiency of the three settings was determined
      by the measured DeltaT values and the DeltaT-ratio between the DeltaT in the
      tumour (DeltaToes) and near the spinal cord (DeltaTcord). For a single patient
      the steady state temperature distribution was computed retrospectively for all
      three settings, since the temperature distributions may be quite different. To
      illustrate that the choice of the optimization strategy is decisive for the
      obtained settings, a numerical optimization on DeltaT-ratio was performed for
      this patient and the steady state temperature distribution for the obtained
      settings was computed. RESULTS: A higher DeltaToes was measured with the mixed
      settings compared to the calculated and clinical settings; DeltaTcord was higher
      with the mixed settings compared to the clinical settings. The DeltaT-ratio was
      approximately 1.5 for all three settings. These results indicate that the most
      effective tumour heating can be achieved with the mixed settings. DeltaT is
      proportional to the Specific Absorption Rate (SAR) and a higher SAR results in a
      higher steady state temperature, which implies that mixed settings are likely to
      provide the most effective heating at steady state as well. The steady state
      temperature distributions for the clinical and mixed settings, computed for the
      single patient, showed some locations where temperatures exceeded the normal
      tissue constraints used in the optimization. This demonstrates that the numerical
      optimization did not prescribe the mixed settings, because it had to comply with
      the constraints set to the normal tissue temperatures. However, the predicted hot
      spots are not necessarily clinically relevant. Numerical optimization on DeltaT
      ratio for this patient yielded a very high DeltaT-ratio ( approximately 380),
      albeit at the cost of excessive heating of normal tissue and lower steady state
      tumour temperatures compared to the conventional optimization. CONCLUSION:
      Treatment planning can be valuable to improve hyperthermia treatments. A thorough
      discussion on clinically relevant objectives and constraints is essential.

PMID- 16891241
TI  - A phase I study to study arsenic trioxide with radiation and hyperthermia in
      advanced head and neck cancer.
AB  - PURPOSE: Arsenic trioxide [ATO] is a pluripotent drug with potentials to have pro
      oxidant, angiogenesis inhibitor, flow inhibitor and radiation sensitizer
      properties. METHODS: The present study is a Phase I trial to assess the safety of
      ATO in advanced or recurrent head and neck cancer treated with radiation and
      hyperthermia. Patients received ATO at 10, 20 and 30 mg per week a day prior to
      hyperthermia. RESULTS: It was assumed that vascular collapse would be complete by
      24 h. Administration of ATO at 20 mg was safe with no toxicity due to ATO. No
      amplification of toxicities due to radiation or hyperthermia was evident.
      Patients without prior treatment showed better response. A total of 11 patients
      were included in this Phase I study. CONCLUSIONS: Patients who received 30 mg of
      ATO weekly showed non-serious acute toxicities. No further escalation of dose was
      attempted.

PMID- 16891242
TI  - The synchronization of chemotherapy to circadian rhythms and irradiation in pre
      operative chemoradiation therapy with hyperthermia for local advanced rectal
      cancer.
AB  - PURPOSE: The therapeutic and adverse effects of pre-operative chrono
      chemoradiation with local hyperthermia for patients with rectal adenocarcinoma
      were evaluated. MATERIALS AND METHODS: Pre-operative radiation therapy of a total
      dose of 40 Gy (n = 10) or 50 Gy (n = 19) on the whole pelvis and hyperthermia
      once a week during the radiation therapy for 1 h were performed for patients with
      T2-T4 rectal adenocarcinoma. Chemotherapy consisted of 5-FU (250 mg m-2 per day)
      and LV (25 mg m-2 per day) administered by continuous infusion in the night for 5
      days a week in the second and fourth weeks of radiation. RESULTS: Grade 3+
      toxicities were seen only in two patients (6.9%). A significant down staging was
      seen in 41.4% of all cases and 52.6% of cases with a radiation dose of 50 Gy. Of
      the patients who had received surgical resection of a tumour, three (11.1%) had
      no residue pathologically in the specimen and eight (29.6%) had microscopic
      lesions. CONCLUSIONS: These results yielded a high response rate with minimal
      toxicities for advanced low-rectal adenocarcinoma. The administration of 5-FU
      during the sleeping time before irradiation might have an advantage not only as a
      chronotherapy but also as a radiation sensitizer.

PMID- 16891243
TI  - Heat-inducible amplifier vector for high-level expression of granulocyte
      macrophage colony-stimulating factor.
AB  - PURPOSE: In cytokine immunotherapy of cancer it is critical to deliver
      sufficiently high local cytokine concentrations in order to reach the therapeutic
      threshold needed for clinical efficacy. Simultaneously, for optimal clinical
      safety adverse effects caused by high systemic cytokine levels must be minimized.
      One of the most promising anti-cancer therapeutic cytokines, granulocyte
      macrophage colony-stimulating factor (GM-CSF), has elicited anti-tumour immune
      responses in animal studies and clinical trials. However, the clinical efficacy
      has been limited, with local GM-CSF levels being therapeutically insufficient and
      systemic toxicity being a limiting factor. METHODS: To address these problems we
      have developed a novel GM-CSF expression vector, pAD-HotAmp-GM-CSF, which can
      provide high levels of GM-CSF expression, and induction of cytokine expression to
      limited tissue areas. This expression system combines inducible and amplifying
      elements in a single multi-genic construct. The first transcriptional unit
      contains the inducible element, the heat shock protein 70B (HSP70B) promoter that
      regulates expression of the transcription-activating factor tat. RESULTS: Upon
      the binding of tat to the second promoter, the HIV2 long terminal repeat
      amplifies downstream gene expression of the therapeutic cytokine GM-CSF. Moderate
      hyperthermia at 42 degrees C for 30 min induced GM-CSF expression in pAD-HotAmp
      GM-CSF that was over 2.5- and 2.8-fold higher than levels reached with HSP70B
      promoter alone and the prototypical human cytomegalovirus promoter. CONCLUSIONS:
      Thus, the inducible amplifier vector, pAD-HotAmp-GM-CSF, represents a novel
      system for regulated and enhanced GM-CSF expression, which enables both greater
      efficacy and safety in cytokine immunotherapy of cancer.

PMID- 16891244
TI  - The effect of post-burn local hyperthermia on the reducing burn injury: the
      possible role of opioids.
AB  - PURPOSE: This paper studied the effect of post-burn local hyperthermia on burn
      induced injury. METHODS: A second-degree burn injury was induced on the right and
      left flanks of Balb/c mice. Thirty-two burn wounds were divided into four groups.
      Opioid receptor blocking was done for groups 3 and 4 by intra-peritoneal
      administration of Naloxone (NLX) 30 min before the thermal injury. Local
      hyperthermia (45 degrees C, 30 s) was applied only for the burn wounds of groups
      2 and 4. Twenty-four hours after burn injury, the burned wounds were assessed for
      the level of iNOS (by immunohistochemistry) and the number of hair follicles (as
      an indicator of tissue injury). RESULTS: The wounds that received hyperthermia
      (group 2) had significantly more hair follicles (p < 0.001) compared to the
      control wounds (group 1). There was no significant difference between the number
      of hair follicles and acute inflammation of group 1 and group 3 (NLX + burn).
      Group 4 (NLX + burn + hyperthermia) had significantly fewer hair follicles
      compared to group 1 (p < 0.001), group 2 (p < 0.001) and group 3 (p < 0.001). The
      level of iNOS in groups 1, 3 and 4 was not significantly different but
      significantly more than group 2 (p < 0.001, p < 0.001 and p < 0.001,
      respectively). CONCLUSIONS: The results showed that local hyperthermia after
      second degree burn decreased the tissue injury and iNOS expression. It is also
      concluded that endogenous opioid response may have a key role in the above
      mentioned effects of post-burn local hyperthermia.

PMID- 16891245
TI  - Thermal medicine, heat shock proteins and cancer.

PMID- 16891247
TI  - In vitro metabolism of the epoxide substructure of cryptophycins by cytosolic
      glutathione S-transferase: species differences and stereoselectivity.
AB  - The enzyme kinetics of the glutathione (GSH) conjugation of cryptophycin 52 (C52,
      R-stereoisomer) and cryptophycin 53 (C53, S-stereoisomer) by cytosolic
      glutathione S-transferases (cGSTs) from human, rat, mouse, dog and monkey liver
      were studied. Vmax, Km, and CLint values for glutathione conjugation of C52 (R
      stereoisomer) were 0.10 +/- 0.01 nmol min-1 mg-1, 3.24 +/- 0.23 microM, and (3.15
      +/- 0.09) x 10(-2) ml min-1 mg-1, respectively, in human cytosol. Due to limited
      solubility relative to the Km, only CLint values were determined in rat ((7.76 +/
      0.10) x 10-2 ml min-1 mg-1) and mouse ((7.61 +/- 0.50) x 10(-2) ml min-1 mg-1)
      cytosol. Enzyme kinetic parameters could not be determined for C53 (S
      stereoisomer). Microsomal GSH conjugation in human, rat, and mouse was attributed
      to cytosolic contamination. No GSH conjugation was seen in any biological matrix
      from dog or monkey. There was little GSH conjugation of C53 by cytosol or
      microsomes from any species. The metabolism of C52 and C53 by epoxide hydrolase
      was also investigated. No diol product was observed in any biological matrix from
      any species. Thus, cGSTs are primarily responsible for C52 metabolism.

PMID- 16891248
TI  - Approach to the prediction of the contribution of major cytochrome P450 enzymes
      to drug metabolism in the early drug-discovery stage.
AB  - It is important to determine the cytochrome P450 (CYP) contribution of certain
      drugs by taking into consideration the attrition due to issues such as genetic
      polymorphism and inter-individual variation. In many cases in the early discovery
      stage, the metabolites of a new chemical have not been identified. Therefore, the
      present paper devised an approach in which the in vitro intrinsic clearance
      (CLint) value for new chemicals was determined by measuring substrate depletion.
      The following prediction methods were compared to calculate CLint using data from
      recombinant CYP enzymes: (1) the relative CYP content in human liver microsomes;
      (2) the relative activity factor (RAF) based on the Vmax value; and (3) the RAF
      value based on the CLint value. The most accurate prediction method was RAF based
      on CLint. This method would be useful in the early drug-discovery process in
      cases in which the main metabolite is not identified.

PMID- 16891249
TI  - CYP2A6 polymorphisms in Malays, Chinese and Indians.
AB  - The genetically polymorphic cytochrome P450 (CYP) 2A6 is the major nicotine
      oxidase in humans that may contribute to nicotine dependence and cancer
      susceptibility. The authors investigated the types and frequencies of CYP2A6
      alleles in the three major ethnic groups in Malaysia and CYP2A6*1A, CYP2A6*1B,
      CYP2A6*1x2, CYP2A6*2, CYP2A6*3, CYP2A6*4, CYP2A6*5, CYP2A6*7, CYP2A6*8 and
      CYP2A6*10 were determined by allele-specific polymerase chain reaction (PCR) in
      270 Malays, 172 Chinese and 174 Indians. Except for CYP2A6*2 and *3 that were not
      detected in the Malays and Chinese, all the other alleles were detected.
      Frequencies for the CYP2A6*4 allele were 7, 5 and 2%, respectively, in Malays,
      Chinese and Indians. A statistically significant high frequency of the duplicated
      CYP2A6*1x2 allele occurred among Chinese. Among Malays and Chinese, the most
      common allele was CYP2A6*1B, but it was CYP2A6*1A among Indians. These ethnic
      difference in frequencies suggested that further studies are required to
      investigate the implications on diseases such as cancer and smoking behaviour
      among these major ethnic groups in Malaysia.

PMID- 16891250
TI  - Biotransformation of cyclosporin in primary rat, porcine and human liver cell co
      cultures.
AB  - The purpose of this study was to investigate the species-specific cyclosporin
      biotransformation in primary rat, human, and porcine liver cell cultures, and to
      investigate the suitability of a modified sandwich culture technique with non
      purified liver cell co-cultures for drug metabolism studies. A sandwich culture
      was found to enhance hepatocellular metabolic activity and improve cellular
      morphology and ultrastructure. The cyclosporin metabolites AM9 and AM1 were
      formed in porcine and human liver cell sandwich co-cultures at levels
      corresponding to the respective in vivo situations. In contrast, metabolite
      profiles in rat hepatocytes were at variance with the in vivo situation. However,
      for all cell types, the overall metabolic activity was positively influenced by
      sandwich co-culture. The initial levels of albumin synthesis were higher in
      sandwich cultures than in those without matrix overlay. It is hypothesized that
      the sandwich culture system provides an improved microenvironment and is,
      therefore, an advantageous tool for in vitro studies of drug metabolism.

PMID- 16891251
TI  - Metabolism of the recently encountered designer drug, methylone, in humans and
      rats.
AB  - The urinary metabolites of methylone in humans and rats were investigated by
      analysing urine specimens from its abuser and after administrating to rats with
      gas chromatography-mass spectrometry (GC-MS) and liquid chromatography
      electrospray ionization mass spectrometry (LC-ESI MS), using authentic standards.
      The time-course excretion profiles of methylone and its three metabolites in rats
      were further investigated after a single intraperitoneal dosing of 5 mg kg-1
      methylone hydrochloride. Two major metabolic pathways were revealed for both
      humans and rats as follows: (1) side-chain degradation by N-demethylation to the
      corresponding primary amine methylenedioxycathinone (MDC), partly conjugated; and
      (2) demethylenation followed by O-methylation of either a 3- or 4-OH group on the
      benzene ring to produce 4-hydroxy-3-methoxymethcathinone (HMMC) or 3-hydroxy-4
      methoxymethcathinone (3-OH-4-MeO-MC), respectively, mostly conjugated. Of these
      metabolites, HMMC was the most abundant in humans and rats. The cumulative amount
      of urinary HMMC excreted within the first 48 h in rats was approximately 26% of
      the dose, and the amount of the parent methylone was not more than 3%. These
      results demonstrate that the analysis of HMMC will be indispensable for proof of
      the use of methylone in forensic urinalysis.

PMID- 16891252
TI  - Kinetics of paraquat in the isolated rat lung: Influence of sodium depletion.
AB  - Paraquat accumulates in the lung through a characteristic polyamine uptake
      system. It has been previously shown that paraquat uptake can be significantly
      prevented if extracellular sodium (Na+) is reduced, although the available data
      correspond to experiments performed using tissue slices or incubated cells. This
      type of in vitro study fails to give information on the actual behaviour
      occurring in vivo since the anatomy and physiology of the studied tissue is
      disrupted. Accordingly, the aim of the present study was to explore the
      usefulness of the isolated rat lung model when applied to characterize the
      kinetic behaviour of paraquat in this tissue after bolus injection under standard
      experimental conditions as well as to evaluate the influence of iso-osmotic
      replacement of Na+ by lithium (Li+) in the perfusion medium. The obtained results
      show that the present isolated rat lung model is useful for the analysis of
      paraquat toxicokinetics, which is reported herein for the first time. It was also
      observed that Na+ depletion in the perfusion medium leads to a decreased uptake
      of paraquat in the isolated rat lung, although it seems that this condition does
      not contribute to improve the elimination of paraquat once the herbicide reaches
      the extravascular structures of the tissue, since the paraquat tissue wash-out
      phase is similar under both experimental conditions assayed.

PMID- 16891254
TI  - Are we too fixated on clinical trial data? The case for using embedded case
      histories to influence prescribing.
AB  - This article examines the assumptions used to support the strategic and tactical
      use of clinical trial data as the main type of information provided by
      pharmaceutical marketers. Evidence is presented which suggests that doctors use
      clinical trial data to construct general beliefs about a disease or product and
      that it is often used incorrectly when assessing the probability that a patient
      has a specific disease. Further evidence is examined which suggests that clinical
      experience is the most important type of information used when doctors make
      specific prescription decisions. A call is made for the pharmaceutical industry
      to address the need for experiential information by examining ways to provide
      doctors with detailed patient case histories.

PMID- 16891255
TI  - Identifying the personality characteristics of healthy eaters and exercisers: a
      hierarchical model approach.
AB  - A study was performed to compare the personality characteristics of healthy
      eating and exercise behavior. The results revealed that a hierarchical model of
      personality accounted for significantly more variance than a version of the Five
      Factor Model. The predictors of health and exercise behaviors were similar. In
      each case, the need for body resources and health motivation were positively
      associated with the outcome variables. In addition, exercise was also positively
      associated with the need for activity and creativity, and negatively related to
      agreeableness.

PMID- 16891256
TI  - Consumer receptiveness to non-traditional roles for community pharmacists.
AB  - Healthcare is in a state of transition as providers are seeking to redefine their
      roles to accommodate marketplace pressures. The focus of this study was to
      examine consumer interest in receiving a portion of their healthcare services
      from community pharmacists. Overall, while consumers see value in pharmacists'
      services directly related to their medications, they may not be thinking of
      pharmacists in broader healthcare roles. If so, a strong marketing program will
      be needed to educate consumers on the qualifications of pharmacists and how there
      is value in the services they could provide.

PMID- 16891257
TI  - Service preferences differences between community pharmacy and supermarket
      pharmacy patrons.
AB  - Differences in service preferences between patrons of supermarket and chain
      pharmacies were determined. Subjects fell into two groups: patrons of a
      supermarket chain's pharmacies and patrons of the same supermarket chain who
      patronized other community chain pharmacies for prescription drug purchases.
      Subjects were asked to prioritize services in terms of convenience and impact on
      pharmacy selection. Differences in service preferences emerged. Community
      pharmacy patrons were more likely to rate easy navigation through a pharmacy and
      24 X 7 hours of operation as key services. Supermarket pharmacy patrons were more
      likely to rate one-stop shopping and adequate hours of operation as priorities.
      Both groups rated basic services such as maintenance of prescription and
      insurance information as priorities. Pharmacies should stress the delivery of
      basic services when trying to attract customers.

PMID- 16891260
TI  - Vitamin D deficiency in community older adults with falls of gait imbalance: an
      under-recognized problem in the inner city.
AB  - INTRODUCTION: Recent reports suggest that vitamin D deficiency is both under
      recognized and undertreated in the geriatric population. In particular, older
      adults with unexplained pain, falls, and gait disorders often may have
      osteomalacia from vitamin D deficiency. Currently, older adults are not screened
      for vitamin D status even when clinical skin suggest deficiency. Our pilot study
      determined the vitamin D status in older, inner city community adults with
      features suggestive of vitamin D deficiency. METHODS: The study was prospective
      and observational. Community-dwelling adults (> 60 years) from our ambulatory
      clinic or in-patient geriatric program, with features compatible with vitamin D
      deficiency (history of falls, gait imbalance, unexplained musculoskeletal pain,
      and/or fractures), were enrolled. IRB approval and signed informed consents were
      obtained. Following a history and physical exam, blood samples for vitamin D
      assay and routine chemistries were obtained. Additional information was collected
      on age, gender, race, dairy product intake, calcium and/or vitamin D supplement
      use, weekly sunlight exposure, season of exam (May-October vs. November-April),
      prior falls and fractures, musculoskeletal pain, and gait disturbances. RESULTS:
      Data were obtained from 48 patients (32F and 16M), mean age of 79 +/- 9 (SD)
      years (range 60-95). Seventy-seven percent of enrollees had gait disturbances,
      77% had a history of falls, 29% had previous fractures and 6% had unexplained
      pain; 79% consumed milk daily, 25% took calcium supplements and 21% used vitamin
      D supplements (in a multivitamin or calcium supplement). Self-reported weekly
      exposure to sunlight ranged from 0 to 42 hours (clothing amount was highly
      variable). Fifty-four percent of this sample had sub-normal vitamin D status
      (serum vitamin D < 20 ng/mL). Patient age (P = 0.2287), gender (P=0.9270),
      exposure to sunlight (P=0.3493), season (P=0.573), and dairy intake (P = 0.735)
      were not associated with vitamin D status. However, 80% of vitamin D supplement
      users versus 37% of non-users had normal vitamin D status (P = 0.029) and 75% of
      calcium supplement users versus 36% of non-users had normal vitamin D status (P =
      0.042). A logistic regression model determined that the use of vitamin D or
      calcium supplements decreased the risk of low vitamin D status by 94% and 93% (P
      = 0.009 and P = 0.010, respectively). CONCLUSION: In this pilot study of older
      adults with gait imbalance and falls, vitamin D deficiency (< 20 ng/mL) was
      observed in 54% of patients tested and previously unrecognized. Higher serum
      vitamin D levels appeared related to the use of vitamin D (in multivitamin or
      calcium supplements) suggesting that deficiency may be preventable and easily
      treated. As vitamin D deficiency is associated with substantial disability, the
      need for increased awareness to screen and prevent this disorder is evident.

PMID- 16891261
TI  - Perceptions of older, low-income women about increasing intake of fruits and
      vegetables.
AB  - Focus groups were conducted with 28 older, low-income women in order to identify
      factors that affected their fruit and vegetable (F&V) consumption. Themes
      emerging from data analysis include barriers to making dietary changes,
      specifically to increasing F&V consumption; beliefs about benefits of consuming
      F&V as compared with other dietary changes; and use of supplements as a
      substitution for eating F&V. A prominent subtheme concerned the conflict women
      felt between their desire to consume more F&V and their desire not to waste food.
      Focus group participants gave concrete suggestions on how to help older, low
      income women increase F&V consumption, which included environmental supports.

PMID- 16891262
TI  - Reliance on others for food-related activities of daily living.
AB  - Reliance on others for help with food-related activities (grocery shopping and
      meal preparation) [FADL] can influence food intake and can be considered part of
      the concept of food security for older adults. Data collected from 193 community
      living seniors identified that 29.5% of these seniors required help with these
      activities. Covariates independently associated with FADL were: muscle
      strength/size, gender, avoidance of activities due to a fear of falling and
      occurrence of functionally limiting diagnoses. Mediation analysis identified
      variables that explain the "how and why" of the association between FADL and food
      intake. Mediators included informal supports, frequency of informal support,
      perceived health status, and number of medications. By specifically analyzing
      covariates and mediators of reliance for FADL, there is further understanding of
      the relationship between this reliance and food intake in older adults.

PMID- 16891263
TI  - Conceptualizing and assessing nutrition needs: perspectives of local program
      providers.
AB  - This study aimed to understand how local Older American Acts Nutrition Program
      (OAANP) providers perceive and assess client need for the OAANP. Qualitative in
      depth interviews were done with a sample of 36 local OAANP providers in upstate
      New York. Providers' perceptions of needs for the OAANP were determined by
      comprehensive understanding of the extent to which an elderly person has problems
      eating properly to maintain good nutritional and health status. Need was
      determined by various aging and environmental factors including food insecurity
      of the elderly, rather than by a single characteristic of problems of elders.
      Efforts to better understand and meet the needs of elders will enable nutrition
      programs to respond to heterogeneous needs in ever increasing older population.

PMID- 16891264
TI  - Management of osteoporosis: a national survey of Israeli dietitians' knowledge
      and perceptions.
AB  - The aim of this study was to assess Israeli dietitians' knowledge and attitudes
      regarding osteoporosis. Participants were 320 dietitians responding to a mail
      survey. Israeli dietitians scored highly on the Facts on Osteoporosis Quiz-FOOQ.
      Israeli dietitians' dietary knowledge regarding calcium (recommended dietary
      allowance, content in food and in supplements) was fairly high; unlike knowledge
      regarding vitamin D. Israeli dietitians had a firm positive opinion of their role
      in the prevention and treatment of osteoporosis.

PMID- 16891268
TI  - PACAP inhibits oxidative stress-induced activation of MAP kinase-dependent
      apoptotic pathway in cultured cardiomyocytes.
AB  - The present article investigated the effect of pituitary adenylate cyclase
      activating polypeptide (PACAP) on oxidative stress-induced apoptosis in neonatal
      rat cardiomyocytes. Our results show that PACAP decreased the ratio of apoptotic
      cells following H2O2 treatment. PACAP also diminished the activity of apoptosis
      signal-regulating kinase. These effects of PACAP were counteracted by the PACAP
      antagonist PACAP6-38. In summary, our results show that PACAP is able to
      attenuate oxidative stress-induced cardiomyocyte apoptosis and suggest that its
      cardioprotective effect is mediated through inhibition of the MAP kinase
      dependent apoptotic pathway.

PMID- 16891270
TI  - Prevention of cervical cancer through vaccination of adolescents.

PMID- 16891269
TI  - Involvement of ERK and CREB signaling pathways in the protective effect of PACAP
      in monosodium glutamate-induced retinal lesion.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) has well-documented
      neuroprotective actions, which have also been shown in retinal degeneration
      induced by monosodium glutamate (MSG) in neonatal rats. The aim of this article
      was to investigate the activation of extracellular signal-regulated kinase
      (ERK1/2) and cyclic adenosine 3',5'-phosphate (cAMP)-responsive element binding
      protein (CREB) signaling pathways by Western blot analysis in retinal
      degeneration induced by MSG. We found that intravitreal administration of PACAP
      preceding the MSG treatments induced significant increases in the
      phosphorylation, that is, the activation of ERK1/2 and its downstream target,
      CREB, 12 h after the treatment compared to the contralateral untreated eye during
      the first two treatments, with no further elevations 24 h after treatments. These
      results demonstrate that the degenerative effect of MSG and the protective effect
      of PACAP involve complex kinase signaling pathways and are related to
      cAMP/ERK/CREB activation.

PMID- 16891271
TI  - Vaccine refusal: issues for the primary care physician.

PMID- 16891272
TI  - Probiotics in primary care pediatrics.
AB  - Probiotics are live microorganisms that help stabilize and balance intestinal
      microflora. Although these organisms are ubiquitous and have been used in the
      production of foods, probiotics have been used more frequently for therapeutic
      purposes, including the treatment and prevention of pediatric diseases. This
      article reviews the proposed mechanisms of the beneficial effects of probiotics,
      potential uses of these organisms in pediatric care, and promising future
      directions for their application.

PMID- 16891273
TI  - Digital rectal examination and the primary care physicians: a lost art?
AB  - Digital rectal examination (DRE) in children is crucial to differentiate between
      simple (habitual) and complicated constipation. Previous experience suggests that
      primary care physicians (PCPs) avoid DRE in children with constipation before
      referral. We evaluated the rate of DRE performance by West Virginian PCPs in
      patients referred to our gastroenterology clinic. Data were collected from the
      physicians' referral letters and parental reports. We found that the vast
      majority (85%) of WV-PCPs do not perform DRE before referring their patients,
      resulting in missed diagnoses and treatment. We concluded that the lack of DRE in
      children with constipation may result in unnecessary referral to the specialist.
      To improve standard of care for children with constipation, an educational
      campaign for PCPs is clearly warranted.

PMID- 16891274
TI  - Toileting concerns, parenting stress, and behavior problems in children with
      special health care needs.
AB  - This study examined the relationship between toileting concerns, behavior
      problems, and parenting stress in parents of children with special health care
      needs (CSHCN). Participants included parents of 99 males and 71 females aged 4 to
      12 years with neural tube defects (NTD), developmental-behavioral disabilities
      (DBD), or history of perinatal intraventricular hemorrhage (IVH). Parents
      completed the Achenbach Child Behavior Checklist (CBCL) and the Parenting Stress
      Index-Short Form (PSI-SF). Parents expressing toileting concerns on the CBCL
      reported significantly more personal distress and more externalizing problems
      versus those with continent children. Variation within subsamples suggested that
      expectations based on nature of disability may be a factor in parent adjustment.
      Direct assessment and intervention of toileting issues should be a high priority
      in secondary stress prevention with CSHCN and their families.

PMID- 16891275
TI  - Targeted child psychiatric services: a new model of pediatric primary clinician-
      child psychiatry collaborative care.
AB  - Between 15% and 25% of children and adolescents seen in pediatric primary care
      have a behavioral health disorder with significant psychopathology, high
      functional impairment, and frequent psychiatric diagnostic comorbidity. Because
      child psychiatry services are frequently unavailable, primary care clinicians are
      frequently left managing these children without access to child psychiatry
      consultation. We describe Targeted Child Psychiatric Services (TCPS), a new model
      of pediatric primary clinician-child psychiatry collaborative care, and describe
      program utilization and characteristics of children referred over the first 18
      months of the program using a retrospective chart review. The TCPS model can
      serve a large number of pediatric primary care practices and provide
      collaborative help with the evaluation and treatment of complex attention deficit
      hyperactivity disorder, depression, anxiety disorders, and pediatric
      psychopharmacology.

PMID- 16891276
TI  - Caustic gastroesophageal lesions in childhood: an analysis of 473 cases.
AB  - Ingested corrosive agents produce oropharyngeal and gastroesophageal injuries
      ranging from minor burns to severe necrosis, depending on the agent amount,
      concentration, and duration of exposure. The aim of this study was to present our
      patients with corrosive ingestion retrospectively. Four hundred seventy-three
      children younger than 16 years of age (mean age, 3.7+/-0.1 years) who were
      admitted to our hospital for suspected corrosive ingestion between the years 1995
      and 2003 were studied. Two hundred eighty-six (60.5%) of 473 patients were males.
      Household bleaches (36.6%) and oven cleaners (23%) were the most frequently
      encountered corrosive agents. During endoscopy, lesions in the esophagus were
      recorded in 379 children. Eighty-one of the cases had gastric lesions. During the
      follow-up, esophageal stricture, esophageal perforation, and gastric outlet
      obstruction (GOO) developed in 11 cases, 1 case, and 2 cases, respectively.
      Caustic ingestion of alkali substances such as oven cleaner seem to cause more
      severe injuries. Early admission to the hospital with clinical and endoscopic
      evaluation and early surgery when required may reduce morbidity and mortality.

PMID- 16891277
TI  - Physicians' attitudes and practices regarding adherence to medical regimens by
      patients with chronic illness.
AB  - Health professionals often do not detect nonadherence despite substantial adverse
      impacts on health-care delivery and costs. We sought to determine how physicians
      assess and manage adherence among patients with chronic illness, and whether
      approaches to nonadherence differ by level of clinical training or prior training
      regarding adherence. Two-hundred seventeen pediatricians and internists completed
      an Internet-based survey. Responses demonstrated that few had previous formal
      training regarding patient adherence. Physicians' assessment of nonadherence and
      knowledge and skills regarding strategies for improving adherence appeared
      significantly more advanced among physicians with more clinical experience and
      among those with formal training in adherence assessment and management. Formal
      educational interventions may improve adherence-related knowledge and skills.

PMID- 16891278
TI  - Extreme thrombocytosis predicts Kawasaki disease in infants.
AB  - Infants with Kawasaki disease are at high risk of developing life-threatening
      coronary complications, yet may elude timely diagnosis because they often lack
      the full complement of classic clinical features. We retrospectively studied
      26,540 children 1 year of age or less who were evaluated at a tertiary care
      pediatric emergency department in whom a platelet count was performed. Among
      those infants with fever without a source identified, 8.5% with platelet counts
      of 800,000 cells/mm(3) or greater had Kawasaki disease compared to 0.4% with
      platelet counts of less than 800,000 cells/mm(3) (likelihood ratio for Kawasaki
      disease was 17 [95% confidence interval, 8-34]). Because many infants present
      atypically, Kawasaki disease should be considered in all children of 1 year or
      less with prolonged fever, extreme elevation of the platelet count, and no
      compelling alternative diagnosis.

PMID- 16891279
TI  - The tale of a belly button: Rieger syndrome.

PMID- 16891280
TI  - Central nervous system hemangioblastoma and von Hippel-Lindau syndrome: a
      familial presentation.

PMID- 16891282
TI  - Atlanto-axial subluxation: a newly reported trampolining injury.

PMID- 16891281
TI  - Metastatic medullary thyroid cancer in a pediatric patient with MEN 2B: emphasis
      on the need for early recognition of extrathyroidal clinical findings associated
      with MEN 2B.

PMID- 16891283
TI  - False positive newborn screens secondary to a maternal inborn error of
      metabolism.

PMID- 16891284
TI  - Rash.

PMID- 16891285
TI  - Persistent pneumonia.

PMID- 16891287
TI  - Statin-induced myopathy: the two faces of Janus.
AB  - Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) have been
      shown to be effective at lowering low-density lipoprotein cholesterol and
      decreasing the risk of coronary heart disease. Although safe and well tolerated
      by most patients, statins have also been associated with muscle-related adverse
      events. This article reviews statin-associated myotoxicity to clarify the
      definitions of muscle-related adverse events and discusses their incidences in
      major statin trials, case reports, and review articles through January 2006.
      Milder complaints (ie, myalgia) are reported by approximately 5% to 7% of
      patients who take statins. More severe myotoxicity, namely rhabdomyolysis, is
      extremely rare for all statins save cerivastatin, and most recent estimates of
      its incidence are between 0.44 and 0.54 cases per 10 000 person-years. The
      mechanism of statin-associated myotoxicity has not been satisfactorily defined
      and is likely due to multiple factors, including membrane instability,
      mitochondrial dysfunction, and defects in myocyte duplication.

PMID- 16891288
TI  - Resistant hypertension: diagnosis and management.
AB  - The incidence of resistant hypertension, the failure to reduce blood pressure
      below 140/90 mm Hg, despite the use of 3 antihypertensive medications at optimal
      doses including a diuretic, is estimated to be less than 5% of the hypertensive
      population. Resistant hypertension increases the risk of stroke, myocardial
      infarction, congestive heart failure, and renal failure. Evaluation of the
      patient with resistant hypertension should include 24-hour ambulatory blood
      pressure monitoring or home measurements and a limited search for secondary
      causes. Treatment should focus on optimizing the drug regimen in a logical way,
      based on the patient's comorbidities and tolerability. Long-acting, well
      tolerated once-daily medications are preferred, and the regimen should include in
      sequence a diuretic, beta-blocker, angiotensin-converting enzyme/angiotensin
      receptor-blocker inhibitors, and a calcium-channel blocker. This article reviews
      the definitions and causes and provides specific recommendations for the
      evaluation and management of patients with this life-threatening condition.

PMID- 16891289
TI  - Comparison of pyrroloquinoline quinone and/or metoprolol on myocardial infarct
      size and mitochondrial damage in a rat model of ischemia/reperfusion injury.
AB  - The cardioprotective effectiveness of low-dose pyrroloquinoline quinone (PQQ, 3
      mg/kg) was compared with metoprolol, a beta(1)-selective adrenoceptor antagonist.
      Rats underwent 30 minutes of left anterior descending coronary artery occlusion
      and 2 hours of reperfusion. Metoprolol and/or PQQ were given at the onset of
      reperfusion to mimic clinical treatment. Metoprolol and/or PQQ reduced infarct
      size and protected against ischemia-induced left ventricular dysfunction after 2
      hours of reperfusion. Combined therapy augmented left ventricular developed
      pressure at the end of reperfusion. Metoprolol or PQQ alone enhanced
      mitochondrial respiratory ratios in ischemic and nonischemic myocardium. Although
      the PQQ/metoprolol combination therapy increased respiratory ratio values, the
      effects were small when compared with PQQ alone. Only PQQ decreased lipid
      peroxidation. Metoprolol and/or PQQ given at the onset of reperfusion reduce
      infarct size and improve cardiac function. Combination therapy further reduces
      infarct size. PQQ is superior to metoprolol in protecting mitochondria from
      ischemia/reperfusion oxidative damage.

PMID- 16891290
TI  - Effect of levosimendan and milrinone on regional myocardial ischemia/reperfusion
      induced arrhythmias in dogs.
AB  - Phosphodiesterase inhibitors as inodilators in heart failure are associated with
      promotion of arrhythmias. Calcium sensitizers have been proposed for the
      treatment of severe decompensated heart failure. The effect of levosimendan, a
      calcium sensitizer, and milrinone, a phosphodiesterase inhibitor, on ventricular
      arrhythmias was compared in a model of acute regional myocardial ischemia and
      reperfusion. The left anterior descending coronary artery in dogs was occluded
      for 25 minutes, followed by reperfusion. The 2 drugs were administered in a
      hemodynamically equieffective dose (0.1 micromol/kg) 10 minutes before coronary
      occlusion. Levosimendan, but not milrinone, significantly attenuated the
      pronounced increase in the number of ventricular premature beats (-63%),
      tachycardia (-50%), fibrillation (-70%), and inhomogeneity of ventricular
      electrical activation. Levosimendan significantly improved the overall survival
      rate. Levosimendan has a more beneficial profile than milrinone regarding the
      development of ventricular arrhythmias during and after regional myocardial
      ischemia.

PMID- 16891291
TI  - Intracoronary administration of abciximab during percutaneous coronary
      interventions: should this be the routine and preferred approach?
AB  - The authors have had experience with administering abciximab as an intracoronary
      bolus in 96 high-risk patients undergoing percutaneous coronary interventions,
      specifically in situations in which there was anticipation of a high embolic load
      from thrombus/plaque burden at the site of the culprit lesion, saphenous vein
      graft culprit lesion, threatened abrupt closure, developing slow-flow, or no
      reflow phenomena with distal embolization. Our uncontrolled data basically
      substantiate the safety of intracoronary administration of abciximab. The data
      summarizing the potential superiority of this method of administration of the
      drug and the likely mechanisms of this effect are summarized. These incite a need
      for reevaluation of the method of administration of the drug, especially in high
      risk percutaneous coronary interventions cases.

PMID- 16891292
TI  - Effects of bezafibrate on HDL2/HDL3 ratio in postmenopausal hypertriglyceridemic
      women.
AB  - The short-term effects of bezafibrate on high-density lipoprotein cholesterol
      quality and triglyceride-rich lipoprotein metabolism in 186 postmenopausal
      hypertriglyceridemic women were investigated. Patients were randomized to an
      untreated group and to bezafibrate (400 mg/d) for 6 months. Fasting lipid
      concentrations, high-density lipoprotein 2, and high-density lipoprotein 3 levels
      were measured at baseline and after 3 and 6 months. At 3 months, bezafibrate had
      significantly decreased mean serum triglycerides and remnant-like particle
      cholesterol levels (105.7 +/- 43.4 mg/dL and 5.33 +/- 2.1 mg/dL, P < .001,
      respectively) from baseline values (232.5 +/- 63.9 mg/dL and 9.69 +/- 3.8 mg/dL,
      respectively). It also maintained lower total cholesterol, low-density
      lipoprotein cholesterol, triglycerides, and remnant-like particle cholesterol
      concentrations to 6 months. After 3 months, it significantly increased mean serum
      high-density lipoprotein cholesterol (55.1 +/- 14.7 vs 64.8 +/- 12.1 mg/dL; P <
      .0001) and maintained higher high-density lipoprotein cholesterol at 6 months.
      The high-density lipoprotein 2-high-density lipoprotein 3 ratio was decreased
      after 3 months of therapy with bezafibrate (2.13 +/- 0.68) from the baseline
      (2.42 +/- 0.71) (P < .01).

PMID- 16891293
TI  - Lack of deleterious interaction between angiotensin receptor blockers and beta
      blockers in the treatment of patients with heart failure.
AB  - The Valsartan-Heart Failure trial formulated the hypothesis that combination
      therapy with angiotensin-converting enzyme inhibitors and beta-blockers with an
      angiotensin-receptor blocker had a deleterious interaction. Furthermore, the Food
      and Drug Administration (FDA)-approved heart failure indication for valsartan
      included the statement that concomitant use of an angiotensin-converting enzyme
      inhibitor, a beta-blocker was not recommended. The Candesartan in Heart Failure
      Assessment of Reduction in Mortality and Morbidity (CHARM)-Added and the
      VALsartan In Acute Myocardial Infarction Trial (VALIANT) provide reassuring
      evidence to support concomitant use of angiotensin-receptor blockers, angiotensin
      converting enzyme inhibitors, and beta-blockers. The FDA-approved heart failure
      indication for candesartan included the statement of additive benefits with
      angiotensin-converting enzyme inhibitors and beta-blockers and led to a change in
      the valsartan label. These considerations have great clinical and public health
      importance given the increasing numbers of patients with heart failure, their
      high morbidity and mortality, and the relatively limited number of effective drug
      therapies.

PMID- 16891294
TI  - Recording of high V1-V3 precordial leads may be essential to the diagnosis of
      Brugada syndrome during the ajmaline test.
AB  - Sodium channel-blocking agents are routinely used to unveil the Brugada syndrome
      in patients in whom the typical electrocardiographic pattern is absent or
      doubtful. In this article, the authors report a patient with syncopal episodes of
      unknown origin in whom the conventional electrocardiographic result was normal
      and a negligibly small "saddle back" type repolarization was present in lead V2
      recorded 2 intercostal spaces above the conventional site. Intravenous ajmaline
      (50 mg) did not elicit the type 1 pattern of the Brugada syndrome in the
      precordial leads obtained at their usual level, but a clear-cut coved-type
      repolarization was apparent in high right precordial leads. These findings
      indicate that high precordial leads should be routinely recorded while assessing
      the ajmaline test in patients suspected of having the Brugada syndrome.

PMID- 16891295
TI  - Heparin therapy leads to platelet activation and prolongation of platelet
      function analyser-100 closure time.

PMID- 16891296
TI  - A meta-analysis of pregnancy outcomes in women with polycystic ovary syndrome.
AB  - Polycystic ovary syndrome (PCOS) is a common reproductive disorder associated
      with many characteristic features, including hyperandrogenaemia, insulin
      resistance and obesity which may have significant implications for pregnancy
      outcomes and long-term health of the woman. This meta-analysis was conducted to
      evaluate the risk of pregnancy and neonatal complications in women with PCOS.
      Electronic databases were searched for the following MeSH headings: PCOS,
      hyperandrogenism, pregnancy outcome, pregnancy complications, diabetes mellitus,
      type II. A handsearch of human reproduction and fertility and sterility was also
      conducted. Studies in which pregnancy outcomes in women with PCOS were compared
      with controls were considered for inclusion in this meta-analysis. Fifteen of 525
      identified studies were included, involving 720 women presenting with PCOS and
      4505 controls. Women with PCOS demonstrated a significantly higher risk of
      developing gestational diabetes [odds ratio (OR) 2.94; 95% confidence interval
      (CI): 1.70-5.08], pregnancy-induced hypertension (OR 3.67; 95% CI: 1.98-6.81),
      pre-eclampsia (OR 3.47; 95% CI: 1.95-6.17) and preterm birth (OR 1.75; 95% CI:
      1.16-2.62). Their babies had a significantly higher risk of admission to a
      neonatal intensive care unit (OR 2.31; 95% CI: 1.25-4.26) and a higher perinatal
      mortality (OR 3.07; 95% CI: 1.03-9.21), unrelated to multiple births. In
      conclusion, women with PCOS are at increased risk of pregnancy and neonatal
      complications. Pre-pregnancy, antenatal and intrapartum care should be aimed at
      reducing these risks.

PMID- 16891297
TI  - A systematic review of tests predicting ovarian reserve and IVF outcome.
AB  - The age-related decline of the success in IVF is largely attributable to a
      progressive decline of ovarian oocyte quality and quantity. Over the past two
      decades, a number of so-called ovarian reserve tests (ORTs) have been designed to
      determine oocyte reserve and quality and have been evaluated for their ability to
      predict the outcome of IVF in terms of oocyte yield and occurrence of pregnancy.
      Many of these tests have become part of the routine diagnostic procedure for
      infertility patients who undergo assisted reproductive techniques. The unifying
      goals are traditionally to find out how a patient will respond to stimulation and
      what are their chances of pregnancy. Evidence-based medicine has progressively
      developed as the standard approach for many diagnostic procedures and treatment
      options in the field of reproductive medicine. We here provide the first
      comprehensive systematic literature review, including an a priori protocolized
      information retrieval on all currently available and applied tests, namely early
      follicular-phase blood values of FSH, estradiol, inhibin B and anti-Mullerian
      hormone (AMH), the antral follicle count (AFC), the ovarian volume (OVVOL) and
      the ovarian blood flow, and furthermore the Clomiphene Citrate Challenge Test
      (CCCT), the exogenous FSH ORT (EFORT) and the gonadotrophin agonist stimulation
      test (GAST), all as measures to predict ovarian response and chance of pregnancy.
      We provide, where possible, an integrated receiver operating characteristic (ROC)
      analysis and curve of all individual evaluated published papers of each test, as
      well as a formal judgement upon the clinical value. Our analysis shows that the
      ORTs known to date have only modest-to-poor predictive properties and are
      therefore far from suitable for relevant clinical use. Accuracy of testing for
      the occurrence of poor ovarian response to hyperstimulation appears to be modest.
      Whether the a priori identification of actual poor responders in the first IVF
      cycle has any prognostic value for their chances of conception in the course of a
      series of IVF cycles remains to be established. The accuracy of predicting the
      occurrence of pregnancy is very limited. If a high threshold is used, to prevent
      couples from wrongly being refused IVF, a very small minority of IVF-indicated
      cases (approximately 3%) are identified as having unfavourable prospects in an
      IVF treatment cycle. Although mostly inexpensive and not very demanding, the use
      of any ORT for outcome prediction cannot be supported. As poor ovarian response
      will provide some information on OR status, especially if the stimulation is
      maximal, entering the first cycle of IVF without any prior testing seems to be
      the preferable strategy.

PMID- 16891298
TI  - Morphogenic protein epimorphin protects intestinal epithelial cells from
      oxidative stress by the activation of EGF receptor and MEK/ERK, PI3 kinase/Akt
      signals.
AB  - Epimorphin is a mesenchymal protein that regulates morphogenesis of epithelial
      cells. Our preliminary study suggested a novel function of epimorphin in
      enhancing survival of intestinal epithelial cells (IEC). Oxidative stress leads
      to cell injury and death and is suggested to be a key contributor to pathogenesis
      of inflammatory bowel disease. This study was conducted to determine whether
      epimorphin protects IEC from oxidative stress. Rat intestinal epithelial cell
      line IEC-6 was cultured with epimorphin (10 and 20 mug/ml), and the life span of
      IEC was assessed. The mean life span of IEC-6 cells was prolonged 1.9-fold (P <
      0.0006) by treatment with epimorphin. We then examined the epimorphin signaling
      pathways. Epimorphin phosphorylated epidermal growth factor (EGF) receptor,
      activated the MEK/extracellular signal-regulated kinase 1/2 mitogen-activated
      protein kinase and phosphatidylinositol 3 (PI3) kinase/Akt pathways,
      phosphorylated Bad, and induced Bcl-X(L) and survivin. Hydrogen peroxide (1 mM)
      induced cell death in 92% of IEC-6 cells, but epimorphin dramatically diminished
      (88.7%) cell death induced by hydrogen peroxide (P < 0.0001). This protective
      effect of epimorphin was significantly attenuated by inhibitors of MEK and PI3
      kinase (P < 0.0001) or EGF receptor-neutralizing antibody (P = 0.0007). In wound
      assays, the number of migrated cells in the wound area decreased (72.5%) by
      treatment with 30 muM hydrogen peroxide, but epimorphin increased the number of
      migrated cells 3.18-fold (P < 0.0001). These results support a novel function of
      epimorphin in protecting IEC from oxidative stress. This anti-oxidative function
      of epimorphin is dramatic and is likely mediated by the activation of EGF
      receptors and the MEK/extracellular signal-regulated kinase and PI3 kinase/Akt
      signaling pathways and through the induction of anti-apoptotic factors.

PMID- 16891299
TI  - Gastric accommodation and motility are influenced by the barostat device:
      Assessment with magnetic resonance imaging.
AB  - The barostat is considered the gold standard for evaluation of proximal gastric
      motility especially for the accommodation response to a meal. The procedure is
      invasive because it involves the introduction of an intragastric catheter and bag
      and is not always well tolerated. Moreover, the barostat bag itself may influence
      motility. Nowadays magnetic resonance imaging (MRI) is able to measure several
      aspects of gastric motility noninvasively. To evaluate whether the accommodation
      response of the stomach, observed with the barostat, is present during MRI and
      whether the barostat interferes with gastric physiology, gastric accommodation,
      motility, and emptying were studied twice in 14 healthy subjects with MRI using
      three-dimensional volume scans and two-dimensional dynamic scans once in the
      presence of a barostat bag and once when the barostat bag was not present.
      Fasting and postprandial intragastric volumes were significantly higher in the
      experiment with barostat vs. without barostat (fasting: 350 +/- 132 ml vs. 37 +/-
      21 ml, P < 0.0001; postprandial: 852 +/- 126 ml vs. 361 +/- 62 ml, P < 0.0001).
      No significant differences were found in gastric emptying (88 +/- 41 vs. 97 +/-
      40 ml/h, not significant) and contraction frequency between both experiments. The
      accommodation response observed in the presence of the barostat bag was not
      observed in the absence of the barostat bag. In conclusion, the presence of an
      intragastric barostat bag does not interfere with gastric emptying or motility,
      but the accommodation response measured with the barostat in situ is not observed
      without the barostat bag in situ. Gastric accommodation is a nonphysiological
      barostat-induced phenomenon.

PMID- 16891300
TI  - Chemokine receptor CCR5 deficiency exacerbates cerulein-induced acute
      pancreatitis in mice.
AB  - Acute pancreatitis (AP) is an inflammatory disease involving the production of
      different cytokines and chemokines and is characterized by leukocyte
      infiltration. Because the chemokine receptor CCR5 and its ligands [the CC
      chemokines CCL3/MIP-1alpha, CCL4/MIP-1beta, and CCL5/regulated upon activation,
      normal T cell expressed and secreted (RANTES)] regulate leukocyte chemotaxis and
      activation, we investigated the expression of CCR5 ligands and the role of CCR5
      and its ligands in experimental AP in mice. AP was induced by hourly
      intraperitoneal injections of cerulein in CCR5-deficient (CCR5(-/-)) or wild-type
      (WT) mice. Induction of AP by cerulein resulted in an early increase of
      pancreatic CCL2, CCL3, and CCL4 mRNA expression, whereas CCL5 mRNA expression
      occurred later. CCR5(-/-) mice developed a more severe pancreatic injury than WT
      mice during cerulein-induced AP, as assessed by a more pronounced increase in
      serum amylase and lipase levels and by more severe pancreatic edema, inflammatory
      infiltrates (mainly neutrophils), and necrosis. CCR5(-/-) mice also exhibited
      increased production of CCL2/MCP-1, CCL3/MIP-1alpha, and CCL4/MIP-1beta during
      the course of cerulein-induced AP. In vivo simultaneous neutralization of CC
      chemokines with monoclonal antibodies in CCR5(-/-) mice reduced the severity of
      cerulein-induced AP, indicating a role of CC chemokines in exacerbating the
      course of AP in the absence of CCR5. Moreover, simultaneous neutralization of
      CCR5 ligands in WT mice also reduced the severity of cerulein-induced AP. In
      conclusion, lack of the chemokine receptor CCR5 exacerbates experimental cerulein
      induced AP and leads to increased levels of CC chemokines and a more pronounced
      pancreatic inflammatory infiltrate, suggesting that CCR5 expression can modulate
      severity of AP.

PMID- 16891301
TI  - Interstitial cells of Cajal and adaptive relaxation in the mouse stomach.
AB  - Interstitial cells of Cajal (ICC) are proposed to play a role in stretch
      activation of nerves and are under intense investigation for potential roles in
      enteric innervation. Most data to support such roles come from in vitro studies
      with muscle strips whereas data at the whole organ level are scarce. To obtain
      insight into the role of ICC in distention-induced motor patterns developing at
      the organ level, we studied distension-induced adaptive relaxation in the
      isolated whole stomach of wild-type and W/W(v) mice. A method was developed to
      assess gastric adaptive relaxation that gave quantitative information on rates of
      pressure development and maximal adaptive relaxation. Pressure development was
      monitored throughout infusion of 1 ml of solution over a 10-min period. The final
      intraluminal pressure was sensitive to blockade of nitric oxide synthase, in wild
      type and W/W(v) mice to a similar extent, indicating NO-mediated relaxation in
      W/W(v) mice. Adaptive relaxation occurred between 0.2 and 0.5 ml of solution
      infusion; this reflex was abolished by TTX, was not sensitive to blockade of
      nitric oxide synthase, but was abolished by apamin, suggesting that ATP and not
      nitric oxide is the neurotransmitter responsible for this intrinsic reflex.
      Despite the absence of intramuscular ICC (ICC-IM), normal gastric adaptive
      relaxation occurred in the W/W(v) stomach. Because pressure development was
      significantly lower in W/W(v) mice compared with wild type in all the conditions
      studied, including in the presence of TTX, ICC-IM may play a role in development
      of myogenic tone. In conclusion, a mouse model was developed to assess the
      intrinsic component of gastric accommodation. This showed that ICC-IM are not
      essential for activation of intrinsic sensory nerves nor ATP-driven adaptive
      relaxation nor NO-mediated relaxation in the present model. ICC-IM may be
      involved in regulation of (distention-induced) myogenic tone.

PMID- 16891302
TI  - An isoflavone conjugate-hydrolyzing beta-glucosidase from the roots of soybean
      (Glycine max) seedlings: purification, gene cloning, phylogenetics, and cellular
      localization.
AB  - Soybeans (Glycine max (L.) Merr.) and certain other legumes excrete isoflavones
      from their roots, which participate in plantmicrobe interactions such as
      symbiosis and as a defense against infections by pathogens. In G. max, the
      release of free isoflavones from their conjugates, the latent forms, is mediated
      by an isoflavone conjugate-hydrolyzing beta-glucosidase. Here we report on the
      purification and cDNA cloning of this important beta-glucosidase from the roots
      of G. max seedlings as well as related phylogenetic and cellular localization
      studies. The purified enzyme, isoflavone conjugate-hydrolyzing beta-glucosidase
      from roots of G. max seedling (GmICHG), is a homodimeric glycoprotein with a
      subunit molecular mass of 58 kDa and is capable of directly hydrolyzing genistein
      7-O-(6 ''-O-malonyl-beta-d-glucoside) to produce free genistein (k(cat), 98 s(
      1); K(m), 25 microM at 30 degrees C, pH 7.0). GmICHG cDNA was isolated based on
      the amino acid sequence of the purified enzyme. GmICHG cDNA was abundantly
      expressed in the roots of G. max seedlings but only negligibly in the hypocotyl
      and cotyledon. An immunocytochemical analysis using anti-GmICHG antibodies, along
      with green fluorescent protein imaging analyses of Arabidopsis cultured cells
      transformed by the GmICHG:GFP fusion gene, revealed that the enzyme is
      exclusively localized in the cell wall and intercellular space of seedling roots,
      particularly in the cell wall of root hairs. A phylogenetic analysis revealed
      that GmICHG is a member of glycoside hydrolase family 1 and can be co-clustered
      with many other leguminous beta-glucosidases, the majority of which may also be
      involved in flavonoid-mediated interactions of legumes with microbes.

PMID- 16891303
TI  - Paraoxonase-2 deficiency aggravates atherosclerosis in mice despite lower
      apolipoprotein-B-containing lipoproteins: anti-atherogenic role for paraoxonase
      2.
AB  - Paraoxonases (PONs) are a family of proteins that may play a significant role in
      providing relief from both toxic environmental chemicals as well as physiological
      oxidative stress. Although the physiological roles of the PON family of proteins,
      PON1, PON2, and PON3, remain unknown, epidemiological, biochemical, and mouse
      genetic studies of PON1 suggest an anti-atherogenic function for paraoxonases. To
      determine whether PON2 plays a role in the development of atherosclerosis in
      vivo, we generated PON2-deficient mice. When challenged with a high fat, high
      cholesterol diet for 15 weeks, serum levels of high density lipoprotein
      cholesterol, triglycerides, and glucose were not significantly different between
      wild-type and PON2-deficient mice. In contrast, serum levels of very low density
      lipoprotein (VLDL)/low density lipoprotein (LDL) cholesterol were significantly
      lower (-32%) in PON2-deficient mice compared with wild-type mice. However,
      despite lower levels of VLDL/LDL cholesterol, mice deficient in PON2 developed
      significantly larger (2.7-fold) atherosclerotic lesions compared with their wild
      type counterparts. Enhanced inflammatory properties of LDL, attenuated anti
      atherogenic capacity of high density lipoprotein, and a heightened state of
      oxidative stress coupled with an exacerbated inflammatory response from PON2
      deficient macrophages appear to be the main mechanisms behind the larger
      atherosclerotic lesions in PON2-deficient mice. These results demonstrate that
      PON2 plays a protective role in atherosclerosis.

PMID- 16891305
TI  - Characterization of amyotrophic lateral sclerosis-linked P56S mutation of vesicle
      associated membrane protein-associated protein B (VAPB/ALS8).
AB  - The P56S mutation in VAPB (vesicle-associated membrane protein-associated protein
      B) causes autosomal dominant motoneuronal diseases. Although it was reported that
      the P56S mutation induces localization shift of VAPB from endoplasmic reticulum
      (ER) to non-ER compartments, it remains unclear what the physiological function
      of VAPB is and how the P56S mutation in VAPB causes motoneuronal diseases. Here
      we demonstrate that overexpression of wild type VAPB (wt-VAPB) promotes unfolded
      protein response (UPR), which is an ER reaction to suppress accumulation of
      misfolded proteins, and that small interfering RNA for VAPB attenuates UPR to
      chemically induced ER stresses, indicating that VAPB is physiologically involved
      in UPR. The P56S mutation nullifies the function of VAPB to mediate UPR by
      inhibiting folding of VAPB that results in insolubility and aggregate formation
      of VAPB in non-ER fractions. Furthermore, we have found that expression of P56S
      VAPB inhibits UPR, mediated by endogenous wt-VAPB, by inducing aggregate
      formation and mislocalization into non-ER fractions of wt-VAPB. Consequently, the
      P56S mutation in a single allele of the VAPB gene may diminish the activity of
      VAPB to mediate UPR to less than half the normal level. We thus speculate that
      the malfunction of VAPB to mediate UPR, caused by the P56S mutation, may
      contribute to the development of motoneuronal degeneration linked to VAPB/ALS8.

PMID- 16891304
TI  - The inhibitor of apoptosis protein fusion c-IAP2.MALT1 stimulates NF-kappaB
      activation independently of TRAF1 AND TRAF2.
AB  - The inhibitors of apoptosis (IAPs) are a family of cell death inhibitors found in
      viruses and metazoans. All members of the IAP family have at least one
      baculovirus IAP repeat (BIR) motif that is essential for their anti-apoptotic
      activity. The t(11, 18)(q21;q21) translocation fuses the BIR domains of c-IAP2
      with the paracaspase/MALT1 (mucosa-associated lymphoid tissue) protein, a
      critical mediator of T cell receptor-stimulated activation of NF-kappaB. The c
      IAP2.MALT1 fusion protein constitutively activates the NF-kappaB pathway, and
      this is considered critical to malignant B cell transformation and lymphoma
      progression. The BIR domains of c-IAP1 and c-IAP2 interact with tumor necrosis
      factor receptor-associated factors 1 and 2 (TRAF1 and TRAF2). Here we
      investigated the importance of TRAF1 and TRAF2 for c-IAP2.MALT1-stimulated NF
      kappaB activation. We identified a novel epitope within the BIR1 domains of c
      IAP1 and c-IAP2 that is crucial for their physical interaction with TRAF1 and
      TRAF2. The c-IAP2.MALT1 fusion protein associates with TRAF1 and TRAF2 using the
      same binding site. We explored the functional relevance of this interaction and
      established that binding to TRAF1 and TRAF2 is not required for c-IAP2.MALT1
      stimulated NF-kappaB activation. Furthermore, gene ablation of TRAF2 or combined
      down-regulation of TRAF1 and TRAF2 did not affect c-IAP2.MALT1-stimulated
      signaling. However, TRAF1/2-binding mutants of c-IAP2.MALT1 still oligomerize and
      activate NF-kappaB, suggesting that oligomerization might be important for
      signaling of the fusion protein. Therefore, the t(11, 18)(q21;q21) translocation
      creating the c-IAP2.MALT1 fusion protein activates NF-kappaB and contributes to
      human malignancy in the absence of signaling adaptors that might otherwise
      regulate its activity.

PMID- 16891306
TI  - Bone marrow-derived cells require a functional glucose 6-phosphate transporter
      for normal myeloid functions.
AB  - Glycogen storage disease type Ib (GSD-Ib) is caused by a deficiency in the
      ubiquitously expressed glucose 6-phosphate transporter (Glc-6-PT). Glc-6-PT
      activity has been shown to be critical in the liver and kidney where a deficiency
      disrupts glucose homeostasis. GSD-Ib patients also have defects in the neutrophil
      respiratory burst, chemotaxis, and calcium flux. They also manifest neutropenia,
      but whether Glc-6-PT deficiency in the bone marrow underlies myeloid dysfunctions
      in GSD-Ib remains controversial. To address this, we transferred bone marrow from
      Glc-6-PT-deficient (Glc-6-PT(-/-)) mice to wild-type mice to generate chimeric
      mice (BM-Glc-6-PT(-/-)). As a control, we also transferred bone marrow between
      wild-type mice (BM-Glc-6-PT(+/+)). While BM-Glc-6-PT(+/+) mice have normal
      myeloid functions, BM-Glc-6-PT(-/-) mice manifest myeloid abnormalities
      characteristic of Glc-6-PT(-/-) mice. Both have impairments in their neutrophil
      respiratory burst, chemotaxis response, and calcium flux activities and exhibit
      neutropenia. In the bone marrow of BM-Glc-6-PT(-/-) and Glc-6-PT(-/-) mice, the
      numbers of myeloid progenitor cells are increased, while in the serum there is an
      increase in granulocyte colony-stimulating factor and chemokine KC levels.
      Moreover, in an experimental model of peritoneal inflammation, local production
      of KC and the related chemokine macrophage inflammatory protein-2 is decreased in
      both BM-Glc-6-PT(-/-) and Glc-6-PT(-/-) mice along with depressed peritoneal
      neutrophil accumulation. The neutrophil recruitment defect was less severe in BM
      Glc-6-PT(-/-) mice than in Glc-6-PT(-/-) mice. These findings demonstrate that
      Glc-6-PT expression in bone marrow and neutrophils is required for normal myeloid
      functions and that non-marrow Glc-6-PT activity also influences some myeloid
      functions.

PMID- 16891307
TI  - Underexpressed coactivators PGC1alpha and SRC1 impair hepatocyte nuclear factor 4
      alpha function and promote dedifferentiation in human hepatoma cells.
AB  - Hepatocyte nuclear factor 4alpha (HNF4alpha) plays critical roles during liver
      development and in the transcriptional regulation of many hepatic genes in adult
      liver. Here we have demonstrated that in human hepatoma HepG2 cells, HNF4alpha is
      expressed at levels as high as in human liver but its activity on target genes is
      very low or absent. We have discovered that the low expression of key
      coactivators (PGC1alpha, SRC1, SRC2, and PCAF) might account for the lack of
      function of HNF4alpha in HepG2 cells. Among them, PGC1alpha and SRC1 are the two
      most important HNF4alpha coactivators as revealed by reporter assays with an Apo
      CIII promoter construct. Moreover, the expression of these two coactivators was
      found to be down-regulated in all human hepatomas investigated. Overexpression of
      SRC1 and PGC1alpha by recombinant adenoviruses led to a significant up-regulation
      of well characterized HNF4alpha-dependent genes (ApoCIII, ApoAV, PEPCK, AldoB,
      OTC, and CYP7A1) and forced HepG2 cells toward a more differentiated phenotype as
      demonstrated by increased ureogenic rate. The positive effect of PGC1alpha was
      seen to be dependent on HNF4alpha. Finally, insulin treatment of human
      hepatocytes and HepG2 cells caused repression of PGC1alpha and a concomitant down
      regulation of ApoCIII, PEPCK, AldoB, and OTC. Altogether, our results suggest
      that SRC1, and notably PGC1alpha, are key coactivators for the proper function of
      HNF4alpha in human liver and for an integrative control of multiple hepatic genes
      involved in metabolism and homeostasis. The down-regulation of key HNF4alpha
      coactivators could be a determinant factor for the dedifferentiation of human
      hepatomas.

PMID- 16891309
TI  - Mutations in the intersubunit bridge regions of 23 S rRNA.
AB  - The large and small subunits of the ribosome are joined by a series of bridges
      that are conserved among mitochondrial, bacterial, and eukaryal ribosomes. In
      addition to joining the subunits together at the initiation of protein synthesis,
      a variety of other roles have been proposed for these bridges. These roles
      include transmission of signals between the functional centers of the two
      subunits, modulation of tRNA-ribosome and factor-ribosome interactions, and
      mediation of the relative movement of large and small ribosomal subunits during
      translocation. The majority of the bridges involve RNA-RNA interactions, and to
      gain insight into their function, we constructed mutations in the 23 S rRNA
      regions involved in forming 7 of the 12 intersubunit bridges in the Escherichia
      coli ribosome. The majority of the mutants were viable in strains expressing
      mutant rRNA exclusively but had distinct growth phenotypes, particularly at 30
      degrees C, and the mutant ribosomes promoted a variety of miscoding errors.
      Analysis of subunit association activities both in vitro and in vivo indicated
      that, with the exception of the bridge B5 mutants, at least one mutation at each
      bridge site affected 70 S ribosome formation. These results confirm the
      structural data linking bridges with subunit-subunit interactions and, together
      with the effects on decoding fidelity, indicate that intersubunit bridges
      function at multiple stages of protein synthesis.

PMID- 16891308
TI  - Yaf2 inhibits caspase 8-mediated apoptosis and regulates cell survival during
      zebrafish embryogenesis.
AB  - Rybp (DEDAF) is a member of the Rybp/Yaf2 protein family and has been shown to
      encode pro-apoptotic functions and to be essential for mouse embryogenesis. The
      related Yaf2 protein has not been studied extensively at the cellular or
      organismal levels. Here we describe zebrafish yaf2 (zyaf2) and show that it is
      widely expressed during early embryogenesis, with subsequent enrichment of
      transcripts in the anterior head region. Depletion of zYaf2 during embryogenesis
      using specific morpholinos activates a wide-spread program of apoptosis and
      causes developmental arrest before the one somite stage. Partial depletion of
      Yaf2, achieved by injecting lower dosages of morpholino, circumvents the early
      arrest but leads to CNS degeneration associated with excessive apoptosis. These
      phenotypes can be rescued by co-injection of human YAF2 mRNA with the morpholinos
      or by treatment with a pan-caspase inhibitor or a caspase 8-specific inhibitor.
      Finally, the observed activation of caspase 8 in the morphants is in accord with
      the ability of Yaf2 to inhibit caspase 8-mediated apoptosis in cultured cells.
      Our findings implicate Yaf2 as a survival factor during early zebrafish
      development and organogenesis. This may suggest that Yaf2 and Rybp can encode
      opposing functions in the regulation of apoptosis.

PMID- 16891311
TI  - Requirement of Smad3 and CREB-1 in mediating transforming growth factor-beta (TGF
      beta) induction of TGF beta 3 secretion.
AB  - Because increased transforming growth factor-beta (TGFbeta) production by tumor
      cells contributes to cancer progression through paracrine mechanisms,
      identification of critical points that can be targeted to block TGFbeta
      production is important. Previous studies have identified the precise signaling
      components and promoter elements required for TGFbeta induction of TGFbeta1
      expression in epithelial cells (Yue, J., and Mulder, K. M. (2000) J. Biol. Chem.
      275, 30765-30773). To determine how regulation of TGFbeta3 expression differs
      from that of TGFbeta1, we identified the precise signaling pathways and
      transcription factor-binding sites that are required for TGFbeta3 gene
      expression. By using mutational analysis in electrophoresis mobility shift assays
      (EMSAs), we demonstrated that the c-AMP-responsive element (CRE) site in the
      TGFbeta3 promoter was required for TGFbeta-inducible TGFbeta3 expression.
      Electrophoresis mobility supershift assays indicated that CRE-binding protein 1
      (CREB1) and Smad3 were the major components present in this TGFbeta-inducible
      complex. Furthermore, by using chromatin immunoprecipitation assays, we
      demonstrated that CREB-1, ATF-2, and c-Jun bound constitutively at the TGFbeta3
      promoter (-100 to +1), whereas Smad3 bound at this site only after TGFbeta
      stimulation. In addition, inhibition of JNK and p38 suppressed TGFbeta induction
      of TGFbeta3 transactivation, whereas inhibition of ERK and protein kinase A had
      no effect. Small interfering RNA-CREB1 and small interfering RNA-Smad3
      significantly inhibited TGFbeta stimulation of TGFbeta3 promoter reporter
      activity and TGFbeta3 production. Our results indicate that TGFbeta activation of
      the TGFbeta3 promoter CRE site, which leads to TGFbeta3 production, is required
      for TGFbetaRII, JNK, p38, and Smad3 but was independent of protein kinase A, ERK,
      and Smad4.

PMID- 16891312
TI  - Identification of a domain in the V0 subunit d that is critical for coupling of
      the yeast vacuolar proton-translocating ATPase.
AB  - Vacuolar proton-translocating ATPase pumps consist of two domains, V(1) and V(o).
      Subunit d is a component of V(o) located in a central stalk that rotates during
      catalysis. By generating mutations, we showed that subunit d couples ATP
      hydrolysis and proton transport. The mutation F94A strongly uncoupled the enzyme,
      preventing proton transport but not ATPase activity. C-terminal mutations changed
      coupling as well; ATPase activity was decreased by 59-72%, whereas proton
      transport was not measurable (E328A) or was moderately reduced (E317A and C329A).
      Except for W325A, which had low levels of V(1)V(o), mutations allowed wild-type
      assembly regardless of the fact that subunits E and d were reduced at the
      membrane. N- and C-terminal deletions of various lengths were inhibitory and
      gradually destabilized subunit d, limiting V(1)V(o) formation. Both N and C
      terminus were required for V(o) assembly. The N-terminal truncation 2-19Delta
      prevented V(1)V(o) formation, although subunit d was available. The C terminus
      was required for retention of subunits E and d at the membrane. In addition, the
      C terminus of its bacterial homolog (subunit C from T. thermophilus) stabilized
      the yeast subunit d mutant 310-345Delta and allowed assembly of the rotor
      structure with subunits A and B. Structural features conserved between bacterial
      and eukaryotic subunit d and the significance of domain 3 for vacuolar proton
      translocating ATPase function are discussed.

PMID- 16891313
TI  - Membrane mucin Muc4 induces density-dependent changes in ERK activation in
      mammary epithelial and tumor cells: role in reversal of contact inhibition.
AB  - The membrane mucin Muc4 has been shown to alter cellular behavior through both
      anti-adhesive effects on cell-cell and cell-extracellular matrix interactions and
      its ability to act as an intramembrane ligand for the receptor tyrosine kinase
      ErbB2. The ERK pathway is regulated by both cell-matrix and cell-cell adhesion.
      An analysis of the effects of Muc4 expression on ERK phosphorylation in mammary
      tumor and epithelial cells, which exhibit both adhesion-dependent growth and
      contact inhibition of growth, showed that the effects are density dependent, with
      opposing effects on proliferating cells and contact-inhibited cells. In these
      cells, cell-matrix interactions through integrins are required for activation of
      the ERK mitogenesis pathway. However, cell-cell interactions via cadherins
      inhibit the ERK pathway. Expression of Muc4 reverses both of these effects. In
      contact-inhibited cells, Muc4 appears to activate the ERK pathway at the level of
      Raf-1; this activation does not depend on Ras activation. The increase in ERK
      activity correlates with an increase in cyclin D(1) expression in these cells.
      This abrogation of contact inhibition is dependent on the number of mucin repeats
      in the mucin subunit of Muc4, indicative of an anti-adhesive effect. The
      mechanism by which Muc4 disrupts contact inhibition involves a Muc4-induced
      relocalization of E-cadherin from adherens junctions at the lateral membrane of
      the cells to the apical membrane. Muc4-induced abrogation of contact inhibition
      may be an important mechanism by which tumors progress from an early, more benign
      state to invasiveness.

PMID- 16891310
TI  - The PDZ scaffold NHERF-2 interacts with mGluR5 and regulates receptor activity.
AB  - The two members of the group I metabotropic glutamate receptor family, mGluR1 and
      mGluR5, both couple to G(q) to mediate rises in intracellular calcium. The
      alternatively spliced C termini (CT) of mGluRs1 and 5are known to be critical for
      regulating receptor activity and to terminate in motifs suggestive of potential
      interactions with PDZ domains. We therefore screened the CTs of both mGluR1a and
      mGluR5 against a PDZ domain proteomic array. Out of 96 PDZ domains examined, the
      domain that bound most strongly to mGluR5-CT was the second PDZ domain of the
      Na(+)/H(+) exchanger regulatory factor 2 (NHERF-2). This interaction was
      confirmed by reverse overlay, and a single point mutation to the mGluR5-CT was
      found to completely disrupt the interaction. Full-length mGluR5 robustly
      associated with full-length NHERF-2 in cells, as assessed by co
      immunoprecipitation and confocal microscopy experiments. In contrast, mGluR1a was
      found to bind NHERF-2 in vitro with a weaker affinity than mGluR5, and
      furthermore mGluR1a did not detectably associate with NHERF-2 in a cellular
      context. Immunohistochemical experiments revealed that NHERF-2 and mGluR5 exhibit
      overlapping patterns of expression in mouse brain, being found most abundantly in
      astrocytic processes and postsynaptic neuronal elements. In functional
      experiments, the interaction of NHERF-2 with mGluR5 in cells was found to prolong
      mGluR5-mediated calcium mobilization and to also potentiate mGluR5-mediated cell
      death, whereas coexpression of mGluR1a with NHERF-2 had no evident effects on
      mGluR1a functional activity. These observations reveal that NHERF-2 can
      selectively modulate mGluR5 signaling, which may contribute to cell-specific
      regulation of mGluR5 activity.

PMID- 16891314
TI  - Glutamine deamidation destabilizes human gammaD-crystallin and lowers the kinetic
      barrier to unfolding.
AB  - Human eye lens transparency requires life long stability and solubility of the
      crystallin proteins. Aged crystallins have high levels of covalent damage,
      including glutamine deamidation. Human gammaD-crystallin (HgammaD-Crys) is a two
      domain beta-sheet protein of the lens nucleus. The two domains interact through
      interdomain side chain contacts, including Gln-54 and Gln-143, which are critical
      for stability and folding of the N-terminal domain of HgammaD-Crys. To test the
      effects of interface deamidation on stability and folding, single and double
      glutamine to glutamate substitutions were constructed. Equilibrium
      unfolding/refolding experiments of the proteins were performed in guanidine
      hydrochloride at pH 7.0, 37 degrees C, or urea at pH 3.0, 20 degrees C. Compared
      with wild type, the deamidation mutants were destabilized at pH 7.0. The proteins
      populated a partially unfolded intermediate that likely had a structured C
      terminal domain and unstructured N-terminal domain. However, at pH 3.0,
      equilibrium unfolding transitions of wild type and the deamidation mutants were
      indistinguishable. In contrast, the double alanine mutant Q54A/Q143A was
      destabilized at both pH 7.0 and 3.0. Thermal stabilities of the deamidation
      mutants were also reduced at pH 7.0. Similarly, the deamidation mutants lowered
      the kinetic barrier to unfolding of the N-terminal domain. These data indicate
      that interface deamidation decreases the thermodynamic stability of HgammaD-Crys
      and lowers the kinetic barrier to unfolding due to introduction of a negative
      charge into the domain interface. Such effects may be significant for cataract
      formation by inducing protein aggregation or insolubility.

PMID- 16891315
TI  - Crystal structure and desulfurization mechanism of 2'-hydroxybiphenyl-2-sulfinic
      acid desulfinase.
AB  - The desulfurization of dibenzothiophene in Rhodococcus erythropolis is catalyzed
      by two monooxygenases, DszA and DszC, and a desulfinase, DszB. In the last step
      of this pathway, DszB hydrolyzes 2'-hydroxybiphenyl-2-sulfinic acid into 2
      hydroxybiphenyl and sulfite. We report on the crystal structures of DszB and an
      inactive mutant of DszB in complex with substrates at resolutions of 1.8A or
      better. The overall fold of DszB is similar to those of periplasmic substrate
      binding proteins. In the substrate complexes, biphenyl rings of substrates are
      recognized by extensive hydrophobic interactions with the active site residues.
      Binding of substrates accompanies structural changes of the active site loops and
      recruits His(60) to the active site. The sulfinate group of bound substrates
      forms hydrogen bonds with side chains of Ser(27), His(60), and Arg(70), each of
      which is shown by site-directed mutagenesis to be essential for the activity. In
      our proposed reaction mechanism, Cys(27) functions as a nucleophile and seems to
      be activated by the sulfinate group of substrates, whereas His(60) and Arg(70)
      orient the syn orbital of sulfinate oxygen to the sulfhydryl hydrogen of Cys(27)
      and stabilize the negatively charged reaction intermediate. Cys, His, and Arg
      residues are conserved in putative proteins homologous to DszB, which are
      presumed to constitute a new family of desulfinases.

PMID- 16891317
TI  - Characterization of a preclinical model of simultaneous breast and ovarian cancer
      progression.
AB  - Women at increased risk for breast cancer are often also at increased risk for
      ovarian cancer, reflecting common risk factors and intertwined etiologies for
      both diseases. Unlike breast cancer prevention, primary ovarian cancer prevention
      has been impractical due to the low incidence, lack of risk and response
      biomarkers and difficulties in sampling ovarian tissue. Challenges in the
      development of ovarian cancer prevention drugs, however, may be circumvented
      through the development of breast cancer prevention strategies that
      simultaneously decrease ovarian cancer. In the present study, three commonly used
      mammary cancer carcinogen models [7,12-dimethylbenz[alpha]anthracene (DMBA), N
      methyl-N-nitrosourea (MNU) and estradiol (E2)] were combined with local ovarian
      DMBA administration to induce progression to mammary and ovarian cancer
      concurrently in the rat. Animals were treated for 3 or 6 months, and tissue
      histology as well as proliferation, hormonal and inflammation biomarkers were
      assessed. Mammary and ovarian morphologies (measured as descriptive histology and
      dysplasia scores) were normal in vehicle controls. Mammary hyperplasia was
      observed in DMBA/DMBA (mammary carcinogen/ovarian carcinogen) and MNU/DMBA
      treated rats; however, ovarian preneoplastic changes were seldom observed after
      these treatments. All E2/DMBA-treated rats had mammary hyperplasia, atypia,
      ductal carcinoma in situ and/or invasive adenocarcinoma, while 50% also developed
      preneoplastic changes in the ovary (ovarian epithelial and stromal hyperplasia
      and inclusion cyst formation). In both the mammary gland and ovary, decreased
      estrogen receptor alpha expression was detected, and in the mammary gland
      elevated Ki-67 and cyclooxygenase-2 expressions were observed. This combined
      breast and ovarian cancer rat model (systemic E2 treatment and local ovarian
      DMBA) may be useful for future dual target breast and ovarian cancer prevention
      studies.

PMID- 16891316
TI  - ATR, PML, and CHK2 play a role in arsenic trioxide-induced apoptosis.
AB  - Arsenic trioxide (ATO) is a potent anti-leukemic chemotherapeutic agent for acute
      promyelocytic leukemia (APL) that results from a t (15, 17) chromosomal
      translocation that produces PML-RARalpha, a fusion protein between a tumor
      suppressor PML and the retinoic acid receptor RARalpha. APL patients are
      initially treated with retinoic acid, but most develop resistance and relapse. In
      contrast, ATO induces prolonged remissions even in the relapsed cases. However,
      the molecular mechanisms by which ATO kills the leukemic cells are not fully
      understood. We find that ATO induces apoptosis, at least in part, by activating
      proapoptotic kinase Chk2. ATO does this by stimulating ATR (ataxia telangiectasia
      mutated and Rad3-related) kinase, a Chk2-activating kinase. In conjunction, ATO
      degrades PML-RARalpha, resulting in the restoration of PML, which is required for
      autophosphorylation and full activation of Chk2. As a result, the p53-dependent
      apoptosis pathway is activated. Based on this, we propose that a pathway composed
      of ATR, PML, Chk2, and p53 plays a role in ATO-mediated apoptosis, a notion that
      is consistent with the observation that Chk2 is genetically intact and mutations
      in the p53 gene are extremely rare in APL.

PMID- 16891318
TI  - TGF-beta and metalloproteinases differentially suppress NKG2D ligand surface
      expression on malignant glioma cells.
AB  - NKG2D ligands (NKG2DL) are expressed by infected and transformed cells. They
      transmit danger signals to NKG2D-expressing immune cells, leading to lysis of
      NKG2DL-expressing cells. We here report that the NKG2DL MHC class I-chain-related
      molecules A and B (MICA/B) and UL16-binding proteins (ULBP) 1-3 are expressed in
      human brain tumours in vivo, while expression levels are low or undetectable in
      normal brain. MICA and ULBP2 expression decrease with increasing WHO grade of
      malignancy, while MICB and ULBP1 are expressed independently of tumour grade. We
      further delineate two independent mechanisms that can explain these expression
      patterns: (i) transforming growth factor-beta (TGF-beta) is upregulated during
      malignant progression and selectively downregulates MICA, ULBP2 and ULBP4
      expression, while MICB, ULBP1 and ULBP3 are unaffected. (ii) Cleavage of MICA and
      ULBP2 is reduced by inhibition of metalloproteinases (MP), whereas no changes in
      the expression levels of other NKG2DL were detected. Consequently, NKG2DL
      dependent NK cell-mediated lysis is enhanced by depletion of TGF-beta or
      inhibition of MP. Thus, escape from NKG2D-mediated immune surveillance of
      malignant gliomas in vivo may be promoted by the inhibition of MICA and ULBP2
      expression via an autocrine TGF-beta loop and by MP-dependent shedding from the
      cell surface. Loss of MICA and ULBP2, in contrast to other NKG2DL, may be
      particularly important in glioma immune escape, and differential regulation of
      human NKG2DL expression is part of the immunosuppressive properties of human
      malignant glioma cells.

PMID- 16891319
TI  - Neuronal atrophy and synaptic alteration in a mouse model of dentatorubral
      pallidoluysian atrophy.
AB  - Dentatorubral-pallidoluysian atrophy (DRPLA) is a hereditary spinocerebellar
      degeneration caused by expansion of a CAG repeat in the disease protein. Despite
      the restricted and stable brain lesions, DRPLA patients show a variety of
      clinical symptoms and the brain exhibits generalized atrophy. In previous studies
      of DRPLA, we proposed that intranuclear diffuse accumulation of the mutant
      protein is a significant pathological feature of neurons, and that the variable
      prevalence of this pathology may be relevant to the variation of symptoms
      observed in patients with different repeat sizes. In this study, to elucidate the
      pathogenesis of the brain atrophy in DRPLA, we conducted morphological and
      statistical analyses of neurons affected by the polyglutamine pathology in DRPLA
      transgenic (Tg) mice with 129 polyglutamine stretches. Golgi-impregnated
      pyramidal neurons in cerebral cortical layer V of 15-week-old Tg mice showed
      significant atrophy of the perikarya and dendrites. Dendritic spines were
      decreased in number and size, and showed a change in morphology resulting in
      dominance of stubby spines. Interestingly, dendritic arborization was preserved.
      Electron microscopy revealed that axons in the pyramis and corpus callosum were
      also atrophic. The number of axonal microtubules was preserved; however, the
      inter-microtubule spacing was significantly decreased. In the neuropil of
      cerebral cortical layers II and III, atrophy of the pre-synaptic areas and
      lengths of the post-synaptic density was detected, but synaptic vesicle diameter
      was preserved. These results suggest that neuronal atrophy is an essential
      feature of the cell pathology in DRPLA and that this is closely related to
      polyglutamine pathogenesis and development of the clinical phenotype.

PMID- 16891320
TI  - Tremor amplitude is logarithmically related to 4- and 5-point tremor rating
      scales.
AB  - Tremor rating scales (TRSs) are used commonly in the clinical assessment of
      tremor, but the relationship of a TRS to actual tremor amplitude has never been
      quantified. Consequently, the resolution of these scales is unknown, and the
      clinical significance of a 1-point change in TRS is uncertain. We therefore
      sought to determine the change in tremor amplitude that corresponds to a 1-point
      change in a typical 5-point TRS. Data from five laboratories were analysed, and
      928 patients with various types of hand tremor were studied. Hand tremor was
      quantified with a graphics tablet in three different labs, an accelerometer in
      three labs and a mechanical-linkage device in one lab. Tremor in writing,
      drawing, horizontal posture, rest and finger-nose testing was graded using a
      variety of TRSs. The relationship between TRS scores and tremor amplitude was
      computed for each task and laboratory. A logarithmic relationship between a 5
      point (0-4) TRS and tremor amplitude (T, measured in centimetres) was found in
      all five labs, despite widely varying rating scales and transducer methodology.
      Thus, T2/T1 = 10(alpha(TRS2-TRS1)). The value of alpha ranged from 0.414 to 0.441
      for writing, 0.355-0.574 for spiral drawing, 0.441 to 0.488 for rest tremor,
      0.266-0.577 for postural tremor and 0.306 for finger-nose testing. For alpha =
      0.3, 0.4, 0.5, 0.6 and 0.7, the ratios T2/T1 for a 1-point decrease in TRS are
      0.501, 0.398, 0.316, 0.251 and 0.200. Therefore, a 1-point change in TRS
      represents a substantial change in tremor amplitude. Knowledge of the
      relationship between TRS and precise measures of tremor is useful in interpreting
      the clinical significance of changes in TRS produced by disease or therapy.

PMID- 16891321
TI  - Circulating monocytes engraft in the brain, differentiate into microglia and
      contribute to the pathology following meningitis in mice.
AB  - Previous studies have demonstrated a potential role of brain endogenous microglia
      and meningeal macrophages in inflammation and brain injury during bacterial
      meningitis. However, the contribution of previously engrafted monocytes and
      microglia to this process is still unknown. We therefore used genetically
      labelled bone marrow-derived cells from transgenic mice expressing the green
      fluorescent protein (GFP) under the chicken beta-actin promoter to deliver
      fluorescently labelled monocytes to the diseased brain. Approximately 24 hours
      after Streptococcus pneumoniae infection, GFP-expressing parenchymal microglia
      changed their morphology to an activated phenotype and upregulated major
      histocompatibility complex class II molecules. Bacterial meningitis increased the
      engraftment of GFP+ monocytes and their differentiation to microglia during the
      post-inflammatory period, but not during acute meningitis. Importantly, these
      newly recruited monocytes became an integral part of the pool of parenchymal
      microglia and contributed to the clearance of damaged tissue by increased
      lysosomal activity and close location to apoptotic cells. Thus, circulating cells
      entering the brain such as monocytes/macrophages might provide a potential
      cellular target for the treatment of the tissue damage following meningitis via
      peripheral cell therapy.

PMID- 16891323
TI  - Longitudinal European surveillance study of antibiotic resistance of Haemophilus
      influenzae.
AB  - OBJECTIVES: We assessed the current resistance rates of Haemophilus influenzae
      against beta-lactams and other agents in Europe and compared the results with
      those of our previously performed surveillance study. METHODS: MICs of the
      antibiotics were determined using broth microdilution. The penicillin-binding
      domain of PBP3 of beta-lactamase (BL)-negative, amoxicillin-resistant (BLNAR)
      isolates was sequenced. RESULTS: The percentage of BL-positive and BLNAR strains
      ranged from 0% to 17.6% and 0% to 33.9%, respectively. Compared with 1997/98 and
      2002/03, the overall percentage of strains non-susceptible to amoxicillin
      decreased from 19.8% and 23.3%, respectively, to 16.4% in 2004/05. The percentage
      of BL-producing strains decreased from 11.0% and 13.7%, respectively, to 7.6%,
      whereas the number of BLNAR strains remained stable (8.8% and 9.6%, respectively,
      versus 8.8% in 2004/05). Comparison of penicillin binding protein (PBP) 3B gene
      sequences between BLNAR and susceptible strains revealed novel amino acid
      mutations. CONCLUSIONS: In spite of large inter-regional differences, the overall
      resistance of H. influenzae to amoxicillin in Europe seems to decline due to a
      decreasing number of BL-producing strains, whereas the overall percentage of
      BLNAR strains seems relatively constant.

PMID- 16891322
TI  - Characterizing physiological heterogeneity of infarction risk in acute human
      ischaemic stroke using MRI.
AB  - Viable tissues at risk of infarction in acute stroke patients have been
      hypothesized to be detectable as volumetric mismatches between lesions on
      perfusion-weighted (PWI) and diffusion-weighted magnetic resonance imaging (DWI).
      Because tissue response to ischaemic injury and to therapeutic intervention is
      tissue- and patient-dependent, changes in infarct progression due to treatment
      may be better detected with voxel-based methods than with volumetric mismatches.
      Acute DWI and PWI were combined using a generalized linear model (GLM) to predict
      infarction risk on a voxel-wise basis for patients treated either with non
      thrombolytic (Group 1; n = 11) or with thrombolytic therapy (Group 2; n = 27).
      Predicted infarction risk for both groups was evaluated in four ipsilateral
      regions of interest: tissue acutely abnormal on DWI (Core), tissue acutely
      abnormal on PWI but normal on DWI that either infarcts (Recruited) or does not
      (Salvaged), and tissue normal on both DWI and PWI that does not infarct (Normal)
      by follow-up imaging > or = 5 days. The performance of the models was
      significantly reduced for the thrombolysed group compared with the group
      receiving standard treatment, suggesting an alteration in natural progression of
      the ischaemic cascade. Average GLM-predicted infarction risk values in the four
      regions were different from one another for both groups. GLM-predicted infarction
      risk in Salvaged tissue was significantly higher (P = 0.02) for thrombolysed
      patients than for non-thrombolysed patients, suggesting that thrombolysis rescued
      tissue with higher infarction risk than typically measured in tissue that
      spontaneously recovered. The observed spatial heterogeneity of GLM-predicted
      infarction risk values probably reflects the varying degrees of tissue injury and
      salvageability that exist after stroke. MRI-based algorithms may therefore
      provide a more sensitive means for monitoring therapeutic effects on a voxel-wise
      basis.

PMID- 16891325
TI  - Co-production of 16S rRNA methylases and extended-spectrum beta-lactamases in
      AmpC-producing Enterobacter cloacae, Citrobacter freundii and Serratia marcescens
      in Korea.

PMID- 16891326
TI  - Emergence of multidrug-resistant Gram-negative bacteria during selective
      decontamination of the digestive tract on an intensive care unit.
AB  - OBJECTIVES: During treatment with selective decontamination of the digestive
      tract (SDD), four multidrug-resistant (MDR) strains, three different Escherichia
      coli and one Klebsiella pneumoniae, were isolated from four patients not known as
      carriers of such MDR strains before their admission to the intensive care unit
      (ICU) in the Academic Medical Center (AMC) in Amsterdam. These isolates were
      extended-spectrum beta-lactamase (ESBL)-positive. We investigated whether this
      was due to interspecies transfer of resistance genes. METHODS: The MDR strains
      were typed by amplified fragment length polymorphism (AFLP) analysis. The
      plasmids from these strains were characterized by restriction fragment length
      polymorphism and the resistance genes were characterized by PCR and sequence
      analysis. RESULTS: The strains were genetically unrelated and contained identical
      plasmids with ESBL genes. CONCLUSIONS: We identified an outbreak of plasmid
      mediated ESBL genes during SDD treatment in the ICU. The use of third-generation
      cephalosporins in SDD is associated with the emergence of ESBLs. We conclude that
      identification of emerging MDR Gram-negative bacteria and recognition of
      resistance plasmid transfer during SDD treatment are crucial for optimal
      application of this regimen in ICUs.

PMID- 16891327
TI  - Diagnostic accuracy of clinical examination for detection of non-cephalic
      presentation in late pregnancy: cross sectional analytic study.
AB  - OBJECTIVE: To examine the diagnostic accuracy of clinical examination to
      determine fetal presentation in late pregnancy. DESIGN: Cross sectional analytic
      study with index test of clinical examination and reference standard of
      ultrasonography. SETTING: Antenatal clinic in tertiary obstetric hospital in
      Sydney, Australia. PARTICIPANTS: 1633 women with a singleton pregnancy between 35
      and 37 weeks' gestation attending antenatal clinics. INTERVENTION: Fetal
      presentation assessed by clinical examination during routine antenatal care,
      followed by ultrasonography to confirm the diagnosis. MAIN OUTCOME MEASURES:
      Sensitivity, specificity, and positive and negative predictive values of clinical
      examination compared with ultrasonography. Diagnostic rates by maternal
      characteristics. RESULTS: Ultrasonography identified non-cephalic presentation in
      130 (8%) women, comprising 103 (6.3%) with breech and 27 (1.7%) with transverse
      or oblique lie. Sensitivity of clinical examination for detecting non-cephalic
      presentation was 70% (95% confidence interval 62% to 78%) and specificity was 95%
      (94% to 96%). The positive predictive value and negative predictive value were
      55% and 97%, respectively. CONCLUSIONS: Clinical examination is not sensitive
      enough for detection and timely management of non-cephalic presentation.

PMID- 16891328
TI  - Effect of needle size on immunogenicity and reactogenicity of vaccines in
      infants: randomised controlled trial.
AB  - OBJECTIVES: To assess the immunogenicity of vaccines for infants and to
      investigate whether the incidence of reactogenicity is reduced after each
      immunisation dose using needles of varying lengths and gauges. DESIGN: Randomised
      controlled trial. SETTING: 18 general practices within two UK primary care
      trusts. PARTICIPANTS: 696 healthy infants vaccinated at 2, 3, and 4 months of
      age, with follow-up to 5 months of age. INTERVENTIONS: Combined diphtheria,
      tetanus, whole cell pertussis, and Haemophilus influenzae type b vaccine and a
      serogroup C meningococcal glycoconjugate vaccine administered using either a
      wide, long needle (23 gauge/0.6 mm diameter, 25 mm), a narrow, short needle (25
      gauge/0.5 mm diameter, 16 mm), or a narrow, long needle (25 gauge, 25 mm). MAIN
      OUTCOME MEASURES: Local and general reactions recorded by parents for three days
      after each dose; and diphtheria, tetanus, and H influenzae type b antibody
      concentrations and functional antibody against serogroup C Neisseria meningitidis
      28-42 days after the third dose. RESULTS: Local reactions to diphtheria, tetanus,
      whole cell pertussis, H influenzae type b vaccinations decreased significantly
      with wide, long needles compared with narrow, short needles. At all three doses
      one less infant experienced local reactions at days 1, 2, or 3 for every six to
      eight vaccinated. Significantly fewer infants vaccinated with the long needle
      experienced severe local reactions. Non-inferiority of the immune response was
      shown using a wide, long needle rather than a narrow, short needle for serogroup
      C meningococcal glycoconjugate vaccine and for diphtheria but not for H
      influenzae type b or tetanus, although no evidence was found of a decrease.
      Little difference was found between needles of the same length but different
      gauges in local reaction or immune response. CONCLUSIONS: Long (25 mm) needles
      for infant immunisations can significantly reduce vaccine reactogenicity at each
      dose while achieving comparable immunogenicity to that of short (16 mm) needles.
      Trial registration Current Controlled Trials ISRCTN62032215 [controlled
      trials.com].

PMID- 16891329
TI  - Retrospective analysis of mode survival, reliability of atrial sensing and
      incidence of atrial tachyarrhythmias in 307 single-lead VDD pacemaker patients.
AB  - AIMS: The aim of this retrospective analysis was to investigate VDD mode
      survival, development of atrial tachyarrhythmias (AT), and long-term atrial
      sensing performance of VDD pacing systems. METHODS AND RESULTS: We implanted
      single-lead VDD pacemakers in patients with isolated atrioventricular block and
      performed a retrospective analysis of 307 patients who had their devices
      implanted between May 1994 and September 2001. In 39 patients (12.7%), the pacing
      mode had to be reprogrammed to a single-chamber ventricular pacing mode, mostly
      due to permanent AT. In 16 of these patients, the atrial sensing safety margin
      was less than 150%. The atrial sensing safety margin was insufficient, i.e. less
      than 100% in only seven patients. Although only 12 (3.9%) of the patients had a
      history of paroxysmal AT at the time of pacemaker implantation, 200 (65%)
      patients presented with AT during follow-up. The mean AT burden at the last
      follow-up was 2.5%. CONCLUSION: These data illustrate that single-lead VDD
      pacemakers can be applied without serious complications in a highly selected
      group of patients. Our main concern is the development of AT in a large part of
      our population. Over a 10-year period, two thirds of our patients presented with
      AT.

PMID- 16891330
TI  - Structural basis for induced-fit binding of Rho-kinase to the inhibitor Y-27632.
AB  - Rho-kinase is a main player in the regulation of cytoskeletal events and a
      promising drug target in the treatment of both vascular and neurological
      disorders. Here we report the crystal structure of the Rho-kinase catalytic
      domain in complex with the specific inhibitor Y-27632. Comparison with the
      structure of PKA bound to this inhibitor revealed a potential induced-fit binding
      mode that can be accommodated by the phosphate binding loop. This binding mode
      resembles to that observed in the Rho-kinase-fasudil complex. A structural
      database search indicated that a pocket underneath the phosphate-binding loop is
      present that favors binding to a small aromatic ring. Introduction of such a ring
      group might spawn a new modification scheme of pre-existing protein kinase
      inhibitors for improved binding capability.

PMID- 16891331
TI  - Use of silkworm larvae to study pathogenic bacterial toxins.
AB  - Injection of stationary phase culture-supernatants of Staphylococcus aureus and
      Pseudomonas aeruginosa into the hemolymph of silkworm larvae caused their death,
      whereas a culture-supernatant of a non-pathogenic strain of Escherichia coli did
      not. A culture-supernatant of a mutant of agr, a global virulence regulator of S.
      aureus that is required for exotoxin production, was much less toxic to silkworm
      larvae. A culture-supernatant of a disruption mutant of the S. aureus beta-toxin
      gene did not kill larvae, whereas one of a deletion mutant of alpha-toxin, gamma
      toxin, or aureolysin killed larvae, indicating that the beta-toxin gene is
      required for staphylococcal supernatant-mediated killing of silkworm larvae. The
      50% lethal doses (LD50) of staphylococcal alpha-toxin and beta-toxin, Pseudomonas
      exotoxin A and diphtheria toxin were 12 microg/g, 9 microg/g, 0.14 microg/g and
      1.1 microg/g, respectively. As the purified toxins killed the larvae, silkworm
      larvae could be used as a model to study the actions of pathogenic bacterial
      toxins in animal bodies.

PMID- 16891332
TI  - The influence of environmental exposure to complex mixtures including PAHs and
      lead on genotoxic effects in children living in Upper Silesia, Poland.
AB  - Environmental exposure is a complex mixture of hazardous compounds with different
      mechanisms of toxicity. In case of concomitant exposure to carcinogenic
      substances--such as polycyclic aromatic hydrocarbons (PAHs)--and to heavy metals-
      such as lead (Pb)--the level of DNA damage may be enhanced. Children are
      considered more vulnerable than adults to chemical toxicants because they take in
      more toxicants as a proportion of body mass and because of inherent biological
      growth and developmental factors. The objective of the study was to measure
      cytogenetic effects in Silesian children and to investigate their relation with
      the environmental exposure to PAHs and Pb. The examined population included 74
      children 5-14-year-old who lived in two cities located in the most polluted
      centre of the Silesia province. Individual exposure to lead was assessed for each
      child by measuring lead in blood (PbB), and to PAH by measuring 1-hydroxypyrene
      in urine (1-OHP), urinary mutagenicity and DNA adducts in circulating
      lymphocytes. Biomarkers of genetic effects were assessed by measuring micronuclei
      (MN) and sister chromatid exchanges (SCE) in children's peripheral lymphocytes.
      The mean levels of biomarkers of exposure were as follows: PbB 7.69 microg/dl,
      DNA adducts 9.59 adducts per 10(8) nt, 1-OHP 0.54 micromol/mol creatinine, and
      urinary mutagenicity presented as the number of revertants per mmol of
      creatinine: 485 for TA 98 and 1318 for YG1024. Mean value of MN was 4.44 per 1000
      binucleated cells and SCE frequency ranged between 6.24 and 10.06 with a mean
      value of 7.87. The results suggest the influence of exposure to environmental
      agents on the induction of cytogenetic effects in peripheral lymphocytes of
      children: namely Pb on MN and PAHs on SCE. The sources of that exposure may be
      outdoor and indoor. Emissions from coal-burning stoves are important contributors
      to the total exposure to PAHs and Pb in Silesian children.

PMID- 16891333
TI  - Plant-environment interactions: Accumulation of hypericin in dark glands of
      Hypericum perforatum.
AB  - BACKGROUND AND AIMS: Hypericum perforatum is a perennial herbaceous plant and an
      extract from this plant has a significant antidepressant effect when administered
      to humans. The plant is characterized by its secretory glands, also known as dark
      glands, which are mainly visible on leaves and flowers. The current study
      evaluates the influence of several environmental factors and developmental stages
      of the plant on the accumulation and synthesis of hypericin and pseudohypericin
      (Hy-G), the major bioactive constituents, in H. perforatum plants. METHODS: The
      appearance of dark glands on different parts of the plant, under several
      environmental conditions, was monitored by microscopy. Hy-G concentrations were
      quantified by high-performance liquid chromatography. KEY RESULTS: A significant
      presence of dark glands accompanying the highest concentrations of Hy-G was
      observed in the stamen tissues more than in any other organ of H. perforatum. A
      linear relationship between the number of dark glands and net photosynthetic rate
      of the leaf and Hy-G concentration in the leaf tissue was also established. A
      very high concentration of Hy-G was measured in the dark-gland tissues, but in
      the tissues without any dark glands it was almost absent. The presence of emodin,
      a precursor of Hy-G, at a high concentration in the dark-gland tissues, and its
      absence in the surrounding tissues was also observed, suggesting that the site of
      biosynthesis of Hy-G is in the dark-gland cells. A significantly low
      concentration of Hy-G (occasionally non-detectable) was measured in the xylem sap
      of the stem tissues. The dark-gland tissues collected from leaves, stems or
      flowers contained similar concentrations of Hy-G. CONCLUSIONS: The concentration
      of Hy-G in various organs of H. perforatum plants is dependent on the number of
      dark glands, their size or area, not on the location of the dark glands on the
      plant. The study provides the first experimental evidence that Hy-G is
      synthesized and accumulates in dark glands.

PMID- 16891334
TI  - Wet-season dormancy release in seed banks of a tropical leguminous shrub is
      determined by wet heat.
AB  - BACKGROUND AND AIMS: Hard-seeded (physical) dormancy is common among plants, yet
      mechanisms for dormancy release are poorly understood, especially in the tropics.
      The following questions are asked: (a) whether dormancy release in seed banks of
      the tropical shrub Parkinsonia aculeata (Caesalpiniaceae) is determined by wet
      heat (incubation under wet, warm to hot, conditions); and (b) whether its effect
      is modified by microclimate. METHODS: A seed burial trial was conducted in the
      wet-dry tropics (northern Australia) to compare dormancy release across different
      habitats (open, artificial cover, ground cover and canopy cover), burial depths
      (0, 3 and 20 cm) and burial durations (2, 6 and 14 weeks). Results were compared
      with predictions using a laboratory-derived relationship between wet heat and
      dormancy release, and microclimate data collected during the trial. KEY RESULTS:
      Wet heat (defined as the soil temperature above which seeds were exposed to field
      capacity or higher for a cumulative total of 24 h) was 43.6 degrees C in the 0 cm
      open treatment, and decreased with increasing shade and depth to 29.5 degrees C
      at 20 cm under canopy cover. The dormancy release model showed that wet heat was
      a good predictor of the proportion of seeds remaining dormant. Furthermore,
      dormancy release was particularly sensitive to wet heat across the temperature
      range encountered across treatments. This resulted in a 16-fold difference in
      dormancy levels between open (<5 % of seeds still dormant) and covered (82 %)
      microhabitats. CONCLUSIONS: These results demonstrate that wet heat is the
      principal dormancy release mechanism for P. aculeata when conditions are hot and
      wet. They also highlight the potential importance of microclimate in driving the
      population dynamics of such species.

PMID- 16891335
TI  - The association between alcohol misuse and suicidal behaviour.
AB  - AIMS: Despite recent small reductions in overall suicide rates, rates among those
      aged 25-44 have remained high. The aim of this paper was to examine the evidence
      for a link between alcohol misuse/consumption and suicidal behaviour, explore the
      reasons for this association, and consider the implications for reducing rates of
      suicidal behaviour. METHODS: A medline search was performed to find relevant
      research evidence. RESULTS: There is evidence to suggest alcohol misuse
      predisposes to suicidal behaviour through its depressogenic effects and promotion
      of adverse life events, and both behaviours may share a common genetic
      predisposition. Acute alcohol use can also precipitate suicidal behaviours
      through induction of negative affect and impairment of problem-solving skills, as
      well as aggravation of impulsive personality traits, possibly through effects on
      serotonergic neurotransmission. CONCLUSIONS: Effective interventions for problem
      drinking may help reduce suicide rates. At a public health level, reducing
      overall alcohol consumption may be beneficial, and the measures shown to be most
      effective in this regard are those that aim to restrict availability of alcohol.

PMID- 16891338
TI  - Preliminary in vivo evidence of increased N-acetyl-aspartate following
      eicosapentanoic acid treatment in patients with bipolar disorder.
AB  - Ethyl-eicosapentanoic acid (ethyl-EPA) may be beneficial in the treatment of
      bipolar disorder (BD) and may have a neurotrophic/neuroprotective role in
      patients with neuropsychiatric disorders. To investigate this we examined whether
      ethyl-EPA treatment of BD patients is associated with increased brain levels of N
      acetylaspartate (NAA), a putative marker of neuronal integrity. Fourteen female
      BD outpatients with moderate depressive symptoms were administered 2 g of ethyl
      EPA per day or placebo for 12 weeks in a randomized, double-blind fashion.
      Quantitative, proton magnetic resonance spectroscopy imaging data were obtained
      prior to randomization and after 12 weeks of treatment from a single 12 ml volume
      of interest centred above the body of the corpus callosum. A significant rise in
      NAA levels was observed in the ethyl-EPA treatment group compared with the
      placebo group (p = 0.027). These results provide the first evidence for a
      probable neurotrophic role of ethyl-EPA treatment in BD underlining the need for
      more detailed investigation of its mechanism of action and therapeutic potential.

PMID- 16891340
TI  - Methylphenidate can reduce selectivity in associative learning in an aversive
      trace conditioning task.
AB  - There are good grounds to expect that methylphenidate (MP) should enhance
      cognitive function. However, experimental evidence on this point is scant. The
      present study therefore examined the effects of MP on learning the association
      between a conditioned stimulus (CS, in this case, noise) and an unconditioned
      stimulus (UCS, in this case, footshock) in an aversive variant of a trace
      conditioning procedure. Learning was measured off-the-baseline as conditioned
      suppression of drinking (both latencies to drink, expressed as suppression
      ratios, and the amount drunk, expressed as the number of licks, in the presence
      of the CS). In addition to the measures of discrete cue conditioning, MP effects
      on contextual conditioning were measured as suppression to apparatus cues and an
      experimental background stimulus. MP was administered at 1 or 5 mg/kg prior to
      conditioning sessions. As attention deficit hyperactivity disorder (ADHD) has
      been characterized as involving a ;wide attentional window' (e.g. Shalev and
      Tsal, 2003), it was predicted that MP, as the treatment of choice for ADHD,
      should increase selectivity (narrowing the attentional window). This outcome
      would show as reduced levels of conditioning (compared to control rats) to less
      informative trace and contextual cues present during conditioning. Contrary to
      prediction, both 1 and 5 mg/kg MP increased learning about all the available
      stimuli, including the less informative trace CS and the background stimulus.
      These findings are consistent with reduced rather than increased selectivity in
      learning (because of increased rather than decreased conditioning to weak cues)
      under MP.

PMID- 16891339
TI  - Aripiprazole use in individuals with intellectual disability and psychotic or
      behavioural disorders: a case series.
AB  - People with intellectual disabilities may be at greater risk of developing
      movement disorders as a consequence of their underlying neurological damage,
      especially when they are treated with typical antipsychotic agents. Aripiprazole
      is a novel antipsychotic quinolone derivative that has been approved for the
      treatment of schizophrenia in adults. However, there are few reports on the use
      of aripiprazole in people with intellectual disabilities. Herein, we report on
      the use of aripiprazole in five individuals with intellectual disabilities and
      psychotic illness (four cases) or challenging behaviour (one case). Four of the
      five patients had an additional diagnosis of schizophrenia and one had autism
      spectrum disorder and challenging behaviour. Issues related to the usefulness of
      aripiprazole in the management of schizophrenia and challenging behaviour in
      people with intellectual disabilities are also discussed. Aripiprazole was well
      tolerated and effective in each of the cases and appears to be a safe and
      efficacious alternative in the management of patients with both intellectual
      disabilities and schizophrenia. It can also be a useful treatment option in the
      management of challenging behaviour, especially when it is used as a part of a
      biopsychosocial approach.

PMID- 16891342
TI  - Electroconvulsive therapy in the treatment of depression in a former ecstasy
      user.
AB  - Depression in former ecstasy users may not respond to selective serotonin
      reuptake inhibitors (SSRIs) possibly due to damaged serotonergic synapses
      following long-term heavy ecstasy use. We report findings in a patient suffering
      from MDMA-induced depression which was refractory to several antidepressive
      medications including selective noradrenergic reuptake inhibitor (SNRI) and SSRI.
      An add-on repeated bilateral electroconvulsive therapy (ECT) was able to achieve
      a stable remission of affective and cognitive symptoms with a follow-up of more
      than 1.5 years. Add-on ECT could be a treatment option in former ecstasy users
      with severe depressive disorders that fail to respond to SSRI and/or SNRI.
      Clinical trials are needed to evaluate further the usefulness of ECT in this
      patient group.

PMID- 16891341
TI  - The resistance to depressive relapse in menopausal women undergoing tryptophan
      depletion: preliminary findings.
AB  - Changes in neuroendocrine function may predispose menopausal women to
      psychological disturbances characterized by depressed mood, anxiety,
      irritability, fatigue, insomnia, forgetfulness and decline in libido. The acute
      tryptophan depletion paradigm was employed to examine the serotonergic
      contribution to mood and cognitive function in menopausal women who were within 4
      weeks of recovery from an episode of major depression. Menopausal women whose
      depression was responsive to treatment with oestradiol, the selective serotonin
      reuptake inhibitor fluoxetine, or a combination of both treatments underwent
      assessment of mood and verbal memory on active tryptophan depLetion and sham
      depletion test days. Although performance on the delayed paragraph recall subtest
      of the Wechsler Memory Scale was impaired by tryptophan depletion, no subjects
      experienced a relapse of depression or a significant worsening of mood. Results
      from this pilot study indicate that menopausal women who have recently recovered
      from a major depressive episode do not experience a worsening of mood with acute
      tryptophan depletion, despite the existence in this sample of some known risk
      factors for depressive relapse as a result of these procedures. While
      preliminary, the results suggest that serotonin may be less critical to the
      pathogenesis of depression during the menopause.

PMID- 16891347
TI  - Arabinan-deficient mutants of Corynebacterium glutamicum and the consequent flux
      in decaprenylmonophosphoryl-D-arabinose metabolism.
AB  - The arabinogalactan (AG) of Corynebacterianeae is a critical macromolecule that
      tethers mycolic acids to peptidoglycan, thus forming a highly impermeable cell
      wall matrix termed the mycolyl-arabinogalactan peptidoglycan complex (mAGP). The
      front line anti-tuberculosis drug, ethambutol (Emb), targets the Mycobacterium
      tuberculosis and Corynebacterium glutamicum arabinofuranosyltransferase Mt-EmbA,
      Mt-EmbB and Cg-Emb enzymes, respectively, which are responsible for the
      biosynthesis of the arabinan domain of AG. The substrate utilized by these
      important glycosyltransferases, decaprenylmonophosphoryl-D-arabinose (DPA), is
      synthesized via a decaprenylphosphoryl-5-phosphoribose (DPPR) synthase (UbiA),
      which catalyzes the transfer of 5-phospho-ribofuranose-pyrophosphate (pRpp) to
      decaprenol phosphate to form DPPR. Glycosyl compositional analysis of cell walls
      extracted from a C. glutamicum::ubiA mutant revealed a galactan core consisting
      of alternating beta(1-->5)-Galf and beta(1-->6)-Galf residues, completely devoid
      of arabinan and a concomitant loss of cell-wall-bound mycolic acids. In addition,
      in vitro assays demonstrated a complete loss of arabinofuranosyltransferase
      activity and DPA biosynthesis in the C. glutamicum::ubiA mutant when supplemented
      with p[14C]Rpp, the precursor of DPA. Interestingly, in vitro
      arabinofuranosyltransferase activity was restored in the C. glutamicum::ubiA
      mutant when supplemented with exogenous DP[14C]A substrate, and C. glutamicum
      strains deficient in ubiA, emb, and aftA all exhibited different levels of DPA
      biosynthesis.

PMID- 16891348
TI  - Dose dependences of radiation induced yield in mixed radiation fields.
AB  - A theoretical model that describes dose dependences of trap filling (radiation
      yield) in mixed radiation fields consisting of two components is proposed. The
      model consists of one type of electron traps and one type of hole traps and
      assumes as an initial step the creation of two types of tracks, each represented
      by some volume with a uniform electron-hole pair density, different for each
      track. The relaxation process that follows comprises interband recombination,
      trapping of electrons and holes, and recombination of electrons with trapped
      holes and of holes with trapped electrons. These processes result in filled traps
      in amounts depending on the absorbed dose in the track and the number and types
      of tracks created in a given region of irradiated matter. The summation over the
      matter with areas of different degrees of overlapping (assuming poisson
      distribution of the created tracks), gives expressions for the dependences of
      trap filling as a function of doses for separated and simultaneous irradiation.
      It is shown that the key parameters determining the behaviour of the dose
      dependences are the ratios between the doses in the separated tracks and the
      average doses delivered on the irradiated matter by the separated components of
      the mixed field. If the ratios of the average dose to the track dose are low, the
      dose dependences will be linear. In the opposite limiting case the dose
      dependencies go to saturation. The linear and additive approximations of dose
      dependences in a mixed field are valid at low doses only.

PMID- 16891349
TI  - Radon and thoron parallel measurements in Hungary.
AB  - Hungarian detectors modified and developed at the National Institute of
      Radiological Sciences (NIRS), Japan were placed at different sites, including
      homes and underground workplaces in Hungary, in order to gain information on the
      average radon (222Rn) and thoron (220Rn) concentration levels. Measurements were
      carried out in dwellings in a village and a manganese mine in Hungary. The radon
      and thoron concentrations in the dwellings of the village in the summer period
      were found to be 154 (17-1083) and 98 (1-714) Bq m(-3), respectively. Considering
      the results of other radon measurements during the winter (814 Bq m(-3)) and
      summer (182 Bq m(-3)) periods, the thoron concentrations were also expected to be
      higher in winter. In the manganese mine, radon and thoron were measured at 20
      points for 6 months, changing the detectors each month. The averages were 924
      (308-1639) and 221 (61-510) Bq m(-3) for radon and thoron, respectively. These
      results showed significant variance with the date and place of the measurement.

PMID- 16891350
TI  - Dose imaging with gel-dosemeter layers: optical analysis and dedicated software.
AB  - In radiotherapy involving thermal and epithermal neutrons, the knowledge of dose
      distributions, with separation of the contribution of each secondary radiation
      component, is of utmost importance. Layers of Fricke-Xylenol-Orange-infused gel
      dosemeters give the possibility of achieving such requirements because, owing to
      the layer-geometry, enriching or depleting the gel matrix of suitable isotopes
      does not sensibly alter neutron transport. The dosimetry method has been
      critically re-examined with the aim of improving its suitability to boron neutron
      capture therapy (BNCT) requirements, as it applies to the protocol of measurement
      and analysis, the sensitivity of the method and the range of the linearity of the
      dosemeters. Software has been developed and studied to obtain automatically the
      images of the various dose components with the established separation procedure.

PMID- 16891351
TI  - An acoustical bubble counter for superheated drop detectors.
AB  - A new bubble counter has been developed based on the well-established approach of
      detecting vaporization events acoustically in superheated drop detectors (SDDs).
      This counter is called the Framework Scientific ABC 1260, and it represents a
      major improvement over prior versions of this technology. By utilizing advanced
      acoustic pattern recognition software, the bubble formation event can be
      differentiated from ambient background noise, as well as from other acoustic
      signatures. Additional structural design enhancements include a relocation of the
      electronic components to the bottom of the device; thus allowing for greater
      stability, easier access to vial SDDs without exposure to system electronics.
      Upgrades in the electronics permit an increase in the speed of bubble detection
      by almost 50%, compared with earlier versions of the counters. By positioning the
      vial on top of the device, temperature and sound insulation can be accommodated
      for extreme environments. Lead shells can also be utilized for an enhanced
      response to high-energy neutrons.

PMID- 16891352
TI  - The effect of meat consumption on body odor attractiveness.
AB  - Axillary body odor is individually specific and potentially a rich source of
      information about its producer. Odor individuality partly results from genetic
      individuality, but the influence of ecological factors such as eating habits are
      another main source of odor variability. However, we know very little about how
      particular dietary components shape our body odor. Here we tested the effect of
      red meat consumption on body odor attractiveness. We used a balanced within
      subject experimental design. Seventeen male odor donors were on "meat" or
      "nonmeat" diet for 2 weeks wearing axillary pads to collect body odor during the
      final 24 h of the diet. Fresh odor samples were assessed for their pleasantness,
      attractiveness, masculinity, and intensity by 30 women not using hormonal
      contraceptives. We repeated the same procedure a month later with the same odor
      donors, each on the opposite diet than before. Results of repeated measures
      analysis of variance showed that the odor of donors when on the nonmeat diet was
      judged as significantly more attractive, more pleasant, and less intense. This
      suggests that red meat consumption has a negative impact on perceived body odor
      hedonicity.

PMID- 16891353
TI  - Laughter among deaf signers.
AB  - The placement of laughter in the speech of hearing individuals is not random but
      "punctuates" speech, occurring during pauses and at phrase boundaries where
      punctuation would be placed in a transcript of a conversation. For speakers,
      language is dominant in the competition for the vocal tract since laughter seldom
      interrupts spoken phrases. For users of American Sign Language, however, laughter
      and language do not compete in the same way for a single output channel. This
      study investigated whether laughter occurs simultaneously with signing, or
      punctuates signing, as it does speech, in 11 signed conversations (with two to
      five participants) that had at least one instance of audible, vocal laughter.
      Laughter occurred 2.7 times more often during pauses and at phrase boundaries
      than simultaneously with a signed utterance. Thus, the production of laughter
      involves higher order cognitive or linguistic processes rather than the low-level
      regulation of motor processes competing for a single vocal channel. In an
      examination of other variables, the social dynamics of deaf and hearing people
      were similar, with "speakers" (those signing) laughing more than their audiences
      and females laughing more than males.

PMID- 16891354
TI  - Comparison of a guaiac based and an immunochemical faecal occult blood test in
      screening for colorectal cancer in a general average risk population.
AB  - BACKGROUND: The guaiac faecal occult blood test (G-FOBT) is recommended as a
      screening test for colorectal cancer but its low sensitivity has prevented its
      use throughout the world. METHODS: We compared the performances of the reference
      G-FOBT (non-rehydrated Hemoccult II test) and the immunochemical faecal occult
      blood test (I-FOBT) using different positivity cut-off values in an average risk
      population sample of 10,673 patients who completed the two tests. Patients with
      at least one test positive were asked to undergo colonoscopy. RESULTS: Using the
      usual cut-off point of 20 ng/ml haemoglobin, the gain in sensitivity associated
      with the use of I-FOBT (50% increase for cancer and 256% increase for high risk
      adenoma) was balanced by a decrease in specificity. The number of extra false
      positive results associated with the detection of one extra advanced neoplasia
      (cancer or high risk adenoma) was 2.17 (95% confidence interval 1.65-2.85). With
      a threshold of 50 ng/ml, I-FOBT detected more than twice as many advanced
      neoplasias as the G-FOBT (ratio of sensitivity = 2.33) without any loss in
      specificity (ratio of false positive rate = 0.99). With a threshold of 75 ng/ml,
      associated with a similar positivity rate to G-FOBT (2.4%), the use of I-FOBT
      allowed a gain in sensitivity of 90% and a decrease in the false positive rate of
      33% for advanced neoplasia. CONCLUSIONS: Evidence in favour of the substitution
      of G-FOBT by I-FOBT is increasing, the gain being more important for high risk
      adenomas than for cancers. The automated reading technology allows choice of the
      positivity rate associated with an ideal balance between sensitivity and
      specificity.

PMID- 16891355
TI  - Human colorectal mucosal O6-alkylguanine DNA-alkyltransferase activity and DNA-N7
      methylguanine levels in colorectal adenoma cases and matched referents.
AB  - BACKGROUND AND AIMS: O(6)-alkylguanine DNA-alkyltransferase (MGMT) provides
      protection against alkylating agent-induced GC-->AT transition mutations. Such
      mutations are frequently seen in the KRAS oncogene of large colorectal adenomas,
      but whether adenoma or mutational risk in humans is influenced by MGMT activity
      and alkylating agent exposure is unclear. Hence, MGMT activity and, as an
      indicator of alkylating agent exposure, DNA-N7-methylguanine (N7-MeG) levels were
      determined in the normal tissue of patients with and without adenomas. METHODS:
      Biopsy specimens of normal colorectal mucosa were collected during colonoscopy
      from 85 patients with histologically proved colorectal adenomas (cases) and from
      85 patients free of gastrointestinal neoplasia (referents) matched by age, sex
      and biopsy location. MGMT activity and N7-MeG levels were measured in colorectal
      tissue extracts and DNA, respectively. RESULTS: MGMT activity was higher in the
      normal mucosa of cases than in referents (6.65+/-3.03 vs 5.61+/-2.74 fmol/micro g
      DNA, p = 0.01). On stratification of cases, MGMT activity was found to be
      considerably greater in the normal mucosa of cases with large adenomas (p =
      0.003) and slightly higher in cases with a GC-->AT transition mutation in the K
      ras gene (p = 0.03). Elevated MGMT levels were associated with an increased risk
      of adenoma (OR 1.17, 95% CI 1.03 to 1.33 per unit increase in activity).
      Detectable levels of N7-MeG were found in DNA from 89% of cases and 93% of
      referents, with levels ranging from <0.1 to 7.7 micro mol/mol dG. Cases and
      referents had similar DNA-N7-MeG levels. CONCLUSIONS: Human exposure to
      methylating agents is widespread. MGMT activity is increased in the normal mucosa
      of patients with adenomas.

PMID- 16891356
TI  - Intrahepatic cholestasis of pregnancy: the severe form is associated with common
      variants of the hepatobiliary phospholipid transporter ABCB4 gene.
AB  - BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP) is characterised by
      troublesome maternal pruritus, raised serum bile acid levels and increased fetal
      risk. Mutations of the ABCB4 gene encoding the hepatobiliary phospholipid
      transporter have been identified in a small proportion of patients with
      cholestasis of pregnancy. In a recent prospective study on 693 patients with
      cholestasis of pregnancy, a cut-off level for serum bile acid (> or =40
      micromol/l) was determined for increased risk of fetal complications. OBJECTIVES:
      To investigate whether common combinations of polymorphic alleles (haplotypes) of
      the genes encoding the hepatobiliary ATP-binding cassette (ABC) transporters for
      phospholipids (ABCB4) and bile acids (ABCB11) were associated with this severe
      form of cholestasis of pregnancy. METHODS: For genetic analysis, 52 women with
      bile acid levels > or =40 micromol/l (called cases) and 52 unaffected women
      (called controls) matched for age, parity and geographical residence were
      studied. Gene variants tagging common ABCB4 and ABCB11 haplotypes were genotyped
      and haplotype distributions were compared between cases and controls by
      permutation testing. RESULTS: In contrast with ABCB11 haplotypes, ABCB4
      haplotypes differed between the two groups (p = 0.019), showing that the severe
      form of cholestasis of pregnancy is associated with the ABCB4 gene variants.
      Specifically, haplotype ABCB4_5 occurred more often in cases, whereas haplotypes
      ABCB4_3 and ABCB4_7 were more common in controls. These associations were
      reflected by different frequencies of at-risk alleles of the two tagging
      polymorphisms (c.711A: odds ratio (OR) 2.27, p = 0.04; deletion intron 5: OR
      14.68, p = 0.012). CONCLUSION: Variants of ABCB4 represent genetic risk factors
      for the severe form of ICP in Sweden.

PMID- 16891357
TI  - Growth factor-like activity of gliadin, an alimentary protein: implications for
      coeliac disease.
AB  - BACKGROUND: Gliadins, a family of wheat proteins, are central to the pathogenesis
      of celiac disease (CD). In addition to 'immunogenic' effects, gliadin directly
      affects cultured cells and intestine preparations, and produces damage in vivo,
      via a separate 'toxic' peptide, such as A-gliadin p31-43 (P31-43). AIMS:
      Understanding the molecular mechanisms underlying direct non T-cell mediated
      effects of gliadin peptides, and assessing their potential role in promoting CD.
      METHOD: Gliadin effects were tested on a number of cell lines and on cultured
      mucosa samples by evaluating cytoskeleton rearrangements, endocytosis,
      proliferation and apoptosis. Standard biochemical methods were used to assess
      prolonged epidermal growth factor receptor (EGFR) activation. RESULTS: Crude
      gliadin peptic-tryptic peptides (PTG], or P31-43 alone, fully reproduce the
      effects of epidermal growth factor (EGF] on actin cytosketon, cell cycle and cell
      proliferation of various cell lines. Inhibitor studies demonstrate the role of
      EGFR in the early response to gliadin exposure, pointing to activation of the
      EGFR pathway. Peptide P31-43 is not similar to any EGFR ligand, but can delay
      inactivation of the EGFR interfering with its endocytosis. Gliadin-induced delay
      of EGFR endocytosis in cultured intestinal biopsies, together with S-phase entry
      of epithelial intestinal cells, confirm a role for EGFR activation in CD.
      CONCLUSION: The ability of gliadin peptides to delay EGFR inactivation through
      interference with the endocytic pathway suggests a model where gliadin fragments
      amplify the effects of trace amounts of EGF, and possibly of other growth
      factors, by prolonging receptor activation. The results, using cultures of
      coeliac intestinal biopsies, highlight the role of the EGF pathway in
      establishing and maintaining the typical atrophic and proliferative alterations
      of the small intestine in CD.

PMID- 16891358
TI  - Treatment of experimental murine pancreatic peritoneal carcinomatosis with
      fibroblasts genetically modified to express IL12: a role for peritoneal innate
      immunity.
AB  - BACKGROUND: Peritoneal carcinomatosis from pancreatic cancer has a poor prognosis
      with a median survival of 3.1 months. This is mainly due to lack of effective
      treatment. Interleukin 12 (IL12) is a proinflammatory cytokine that has a potent
      antitumoral effect by stimulating innate and adoptive immunity. AIM: To examine
      the antitumoral effect and toxicity of intraperitoneal delivery of IL12 using an
      ex vivo gene therapy approach in a murine model of pancreatic peritoneal
      carcinomatosis. METHODS: Peritoneal carcinomatosis was generated by direct
      intraperitoneal inoculation of the pancreatic cancer cell line Capan-1 in athymic
      mice. Syngenic fibroblasts were genetically modified in vitro to secrete IL12
      using a polycistronic TFG murine IL12 retroviral vector coding for both p35 and
      p40 murine IL12 subunits. Ex vivo gene therapy involved injection of the
      genetically modified fibroblasts intraperitoneally twice a week for 4 weeks.
      RESULTS: Treatment of pre-established peritoneal carcinomatosis with fibroblasts
      genetically modified to express IL12 induced a marked inhibition of tumour growth
      as measured by comparison of the weights of the intraperitoneal tumour nodules in
      the treated and control animals (3.52 (SD 0.47) v 0.93 (SD 0.21) g, p<0.05) and
      improved survival. This effect was associated with infiltration of the peritoneal
      tumour nodules with macrophages. Peritoneal lavage confirmed enhancement of the
      innate peritoneal inflammatory activity, with an increased number of activated
      macrophages and natural killer cells. Moreover, macrophages harvested from
      animals with peritoneal carcinomatosis and treated with IL12-expressing
      fibroblasts expressed an activated proinflammatory antitumoral M1 phenotype that
      included strongly enhanced reactive oxygen species and nitric oxide production.
      There was no treatment-related toxicity. CONCLUSION: Multiple injections of
      genetically modified fibroblasts to express IL12 is an effective and well
      tolerated treatment for experimental murine pancreatic peritoneal carcinomatosis
      via activated innate immunity and in particular activated M1 macrophages.

PMID- 16891359
TI  - A computational study of nucleosomal DNA flexibility.
AB  - Molecular dynamics simulations of the nucleosome core particle and its isolated
      DNA free in solution are reported. The simulations are based on the implicit
      solvent methodology and provide insights into the nature of large-scale
      structural fluctuations and flexibility of the nucleosomal DNA. In addition to
      the kinked regions previously identified in the x-ray structure of the
      nucleosome, the simulations support the existence of a biochemically identified
      distorted region of the DNA. Comparison of computed relative free energies shows
      that formation of the kinks is associated with little, if any, energy cost
      relative to a smooth, ideal conformation of the DNA superhelix. Isolated
      nucleosomal DNA is found to be considerably more flexible than expected for a 147
      bp stretch of DNA based on its canonical persistence length of 500 A. Notably,
      the significant bending of the DNA observed in our simulations occurs without
      breaking of Watson-Crick bonds. The computed relative stability of bent
      conformations is sensitive to the ionic strength of the solution in the
      physiological range; the sensitivity suggests possible experiments that might
      provide further insights into the structural origins of the unusual flexibility
      of the DNA.

PMID- 16891360
TI  - Analysis of transient behavior in complex trajectories: application to secretory
      vesicle dynamics.
AB  - Analysis of trajectories of dynamical biological objects, such as breeding ants
      or cell organelles, is essential to reveal the interactions they develop with
      their environments. Many previous works used a global characterization based on
      parameters calculated for entire trajectories. In cases where transient behavior
      was detected, this usually concerned only a particular type, such as confinement
      or directed motion. However, these approaches are not appropriate in situations
      in which the tracked objects may display many different types of transient
      motion. We have developed a method to exhaustively analyze different kinds of
      transient behavior that the tracked objects may exhibit. The method discriminates
      stalled periods, constrained and directed motions from random dynamics by
      evaluating the diffusion coefficient, the mean-square displacement curvature, and
      the trajectory asymmetry along individual trajectories. To detect transient
      motions of various durations, these parameters are calculated along trajectories
      using a rolling analysis window whose width is variable. The method was applied
      to the study of secretory vesicle dynamics in the subplasmalemmal region of human
      carcinoid BON cells. Analysis of transitions between transient motion periods,
      combined with plausible assumptions about the origin of each motion type, leads
      to a model of dynamical subplasmalemmal organization.

PMID- 16891361
TI  - Lateral mobility of membrane-binding proteins in living cells measured by total
      internal reflection fluorescence correlation spectroscopy.
AB  - Total internal reflection fluorescence correlation spectroscopy (TIR-FCS) allows
      us to measure diffusion constants and the number of fluorescent molecules in a
      small area of an evanescent field generated on the objective of a microscope. The
      application of TIR-FCS makes possible the characterization of reversible
      association and dissociation rates between fluorescent ligands and their
      receptors in supported phospholipid bilayers. Here, for the first time, we extend
      TIR-FCS to a cellular application for measuring the lateral diffusion of a
      membrane-binding fluorescent protein, farnesylated EGFP, on the plasma membranes
      of cultured HeLa and COS7 cells. We detected two kinds of diffusional motion-fast
      three-dimensional diffusion (D(1)) and much slower two-dimensional diffusion
      (D(2)), simultaneously. Conventional FCS and single-molecule tracking confirmed
      that D(1) was free diffusion of farnesylated EGFP close to the plasma membrane in
      cytosol and D(2) was lateral diffusion in the plasma membrane. These results
      suggest that TIR-FCS is a powerful technique to monitor movement of membrane
      localized molecules and membrane dynamics in living cells.

PMID- 16891362
TI  - Unbinding of retinoic acid from the retinoic acid receptor by random expulsion
      molecular dynamics.
AB  - Unbinding pathways of retinoic acid (RA) bound to retinoic acid receptor (RAR)
      have been explored by the random expulsion molecular dynamics (REMD) method. Our
      results show that RA may exit the binding site of RAR through flexible regions
      close to the H1-H3 loop and beta-sheets, without displacing H12 from its agonist
      position. This result may explain kinetic differences between agonist and
      antagonist ligands observed for other nuclear receptors. The extended and
      flexible structure of RA initiated a methodological study in a simplified two
      dimensional model system. The REMD force should in general be distributed to all
      atoms of the ligand to obtain the most unbiased results, but for a ligand which
      is tightly bound in the binding pocket through a strong electrostatic
      interaction, application of the REMD force on a single atom is preferred.

PMID- 16891364
TI  - Strain-dependent kinetics of the myosin working stroke, and how they could be
      probed with optical-trap experiments.
AB  - The strain-dependent kinetics of the myosin working stroke under load is derived
      from a flat-energy-landscape model for its untethered lever-arm, and compared
      with other scenarios in the literature. The "flat landscape" scenario is
      compatible with muscle-fiber experiments, but is more critically relevant to
      single-myosin experiments with an optically trapped actin filament. In such
      experiments, the strain dependence of stroke kinetics may be explored by
      comparing event-averaged and time-averaged displacements of the filament. With a
      specific kinetic model of the cross-bridge cycle, we have previously shown that
      the event-averaged displacement underestimates the working stroke. Here we
      predict that the two kinds of averaging give diverging estimates of the working
      stroke as the resolving time of the event detector is decreased to 1 ms or less,
      the discrepancy being critically dependent on the strain dependence of the stroke
      rate. Such analysis of trap displacement data offers the possibility of testing
      the strain-dependent stroke rate predicted by the flat-landscape model.

PMID- 16891363
TI  - Reversible thermal denaturation of a 60-kDa genetically engineered beta-sheet
      polypeptide.
AB  - A de novo 687-amino-acid residue polypeptide with a regular 32-amino-acid repeat
      sequence, (GA)(3)GY(GA)(3)GE(GA)(3)GH(GA)(3)GK, forms large beta-sheet
      assemblages that exhibit remarkable folding properties and, as well, form
      fibrillar structures. This construct is an excellent tool to explore the details
      of beta-sheet formation yielding intimate folding information that is otherwise
      difficult to obtain and may inform folding studies of naturally occurring
      materials. The polypeptide assumes a fully folded antiparallel beta-sheet/turn
      structure at room temperature, and yet is completely and reversibly denatured at
      125 degrees C, adopting a predominant polyproline II conformation. Deep
      ultraviolet Raman spectroscopy indicated that melting/refolding occurred without
      any spectroscopically distinct intermediates, yet the relaxation kinetics depend
      on the initial polypeptide state, as would be indicative of a non-two-state
      process. Thermal denaturation and refolding on cooling appeared to be
      monoexponential with characteristic times of approximately 1 and approximately 60
      min, respectively, indicating no detectable formation of hairpin-type nuclei in
      the millisecond timescale that could be attributed to nonlocal "nonnative"
      interactions. The polypeptide folding dynamics agree with a general property of
      beta-sheet proteins, i.e., initial collapse precedes secondary structure
      formation. The observed folding is much faster than expected for a protein of
      this size and could be attributed to a less frustrated free-energy landscape
      funnel for folding. The polypeptide sequence suggests an important balance
      between the absence of strong nonnative contacts (salt bridges or hydrophobic
      collapse) and limited repulsion of charged side chains.

PMID- 16891365
TI  - Rheology of passive and adhesion-activated neutrophils probed by atomic force
      microscopy.
AB  - The rheology of neutrophils in their passive and activated states plays a key
      role in determining their function in response to inflammatory stimuli. Atomic
      force microscopy was used to study neutrophil rheology by measuring the complex
      shear modulus G*(omega) of passive nonadhered rat neutrophils on poly(HEMA) and
      neutrophils activated through adhesion to glass. G*(omega) was measured over
      three frequency decades (0.1-102.4 Hz) by indenting the cells 500 nm with a
      spherical tip and then applying a 50-nm amplitude multi-frequency signal.
      G*(omega) of both passive and adhered neutrophils increased as a power law with
      frequency, with a coupling between elastic (G') and loss (G'') moduli. For
      passive neutrophils at 1.6 Hz, G' = 380 +/- 121 Pa, whereas G'' was fourfold
      smaller and the power law coefficient was of x = 1.184. Adhered neutrophils were
      over twofold stiffer with a lower slope (x = 1.148). This behavior was adequately
      described by the power law structural damping model but not by liquid droplet and
      Kelvin models. The increase in stiffness with frequency may modulate neutrophil
      transit, arrest, and transmigration in vascular microcirculation.

PMID- 16891366
TI  - Localization of the pH gate in Kir1.1 channels.
AB  - We used cysteine-modifying reagents to localize the pH-sensitive gate in the
      renal inward-rectifier K(+) channel Kir1.1a (ROMK1). Cytoplasmic-side
      methanethiosulfonate (MTS) reagents blocked K(+) permeation in native Kir1.1
      channels, expressed in Xenopus oocytes. Replacement of three cysteines in the N
      terminus, C-terminus, and transmembrane domains eliminated this sensitivity to
      MTS reagents, as measured with inside-out macropatches. Reintroduction of one
      cysteine at 175-Kir1.1a in the second transmembrane domain allowed blockade of
      the open channel by the MTS reagents MTSEA, MTSET, and MTSES and by Ag(+).
      However, closure of the channel by low pH protected it from modification.
      Cysteine was also introduced into position G223, which is thought to line the
      cytoplasmic pore of the channel. MTSET blocked G223C in both the open and closed
      state. In contrast, MTSEA reduced G223C single-channel conductance from 40 to 23
      pS but did not produce complete block. We conclude that cytoplasmic acidification
      induces a conformational change in the channel protein that prevents access of
      cysteine-modifying reagents, and presumably also K(+) ions, to the transmembrane
      pore from the cytoplasm. This is consistent with localization of the Kir1.1 pH
      gate at the helix bundle crossing near the cytoplasmic end of the transmembrane
      pore.

PMID- 16891367
TI  - Optimization and evaluation of a coarse-grained model of protein motion using x
      ray crystal data.
AB  - Simple coarse-grained models, such as the Gaussian network model, have been shown
      to capture some of the features of equilibrium protein dynamics. We extend this
      model by using atomic contacts to define residue interactions and introducing
      more than one interaction parameter between residues. We use B-factors from 98
      ultra-high resolution (<or=1.0 A) x-ray crystal structures to optimize the
      interaction parameters. The average correlation between Gaussian network-model
      fluctuation predictions and the B-factors is 0.64 for the data set, consistent
      with a previous large-scale study. By separating residue interactions into
      covalent and noncovalent, we achieve an average correlation of 0.74, and addition
      of ligands and cofactors further improves the correlation to 0.75. However,
      further separating the noncovalent interactions into nonpolar, polar, and mixed
      yields no significant improvement. The addition of simple chemical information
      results in better prediction quality without increasing the size of the coarse
      grained model.

PMID- 16891368
TI  - A model structure for the heterodimer apoA-IMilano-apoA-II supports its peculiar
      susceptibility to proteolysis.
AB  - In this study, we propose a structure for the heterodimer between apolipoprotein
      A-I(Milano) and apolipoprotein A-II (apoA-I(M)-apoA-II) in a synthetic high
      density lipoprotein (HDL) containing L-alpha-palmitoyloleoyl phosphatidylcholine.
      We applied bioinformatics/computational tools and procedures, such as molecular
      docking, molecular and essential dynamics, starting from published crystal
      structures for apolipoprotein A-I and apolipoprotein A-II. Structural and
      energetic analyses onto the simulated system showed that the molecular dynamics
      produced a stabilized synthetic HDL. The essential dynamic analysis showed a
      deviation from the starting belt structure. Our structural results were validated
      by limited proteolysis experiments on HDL from apoA-I(M) carriers in comparison
      with control HDL. The high sensitivity of apoA-I(M)-apoA-II to proteases was in
      agreement with the high root mean-square fluctuation values and the reduction in
      secondary structure content from molecular dynamics data. Circular dichroism on
      synthetic HDL containing apoA-I(M)-apoA-II was consistent with the alpha-helix
      content computed on the proposed model.

PMID- 16891370
TI  - Curvature elasticity and refolding of OmpA in large unilamellar vesicles.
AB  - The stability of OmpA in large unilamellar vesicles of dilauroyl
      phosphatidylcholine was studied using different concentrations of urea. The
      effective energy of unfolding, as determined from refolding experiments, is
      greater than that for small sonicated unilamellar vesicles by an amount that is
      compatible with estimates of the elastic energy of highly curved vesicles. The on
      rate for refolding and insertion is slower for large unilamellar vesicles than
      for small unilamellar vesicles, which indicates a contribution of vesicle strain
      also to the free energy of the transition state.

PMID- 16891369
TI  - Microrheology and ROCK signaling of human endothelial cells embedded in a 3D
      matrix.
AB  - Cell function is profoundly affected by the geometry of the extracellular
      environment confining the cell. Whether and how cells plated on a two-dimensional
      matrix or embedded in a three-dimensional (3D) matrix mechanically sense the
      dimensionality of their environment is mostly unknown, partly because individual
      cells in an extended matrix are inaccessible to conventional cell-mechanics
      probes. Here we develop a functional assay based on multiple particle tracking
      microrheology coupled with ballistic injection of nanoparticles to measure the
      local intracellular micromechanical properties of individual cells embedded
      inside a matrix. With our novel assay, we probe the mechanical properties of the
      cytoplasm of individual human umbilical vein endothelial cells (HUVECs) embedded
      in a 3D peptide hydrogel in the presence or absence of vascular endothelial
      growth factor (VEGF). We found that VEGF treatment, which enhances endothelial
      migration, increases the compliance and reduces the elasticity of the cytoplasm
      of HUVECs in a matrix. This VEGF-induced softening response of the cytoplasm is
      abrogated by specific Rho-kinase (ROCK) inhibition. These results establish
      combined particle-tracking microrheology and ballistic injection as the first
      method able to probe the micromechanical properties and mechanical response to
      agonists and/or drug treatments of individual cells inside a matrix. These
      results suggest that ROCK plays an essential role in the regulation of the
      intracellular mechanical response to VEGF of endothelial cells in a 3D matrix.

PMID- 16891371
TI  - Examining the influence of linkers and tertiary structure in the forced unfolding
      of multiple-repeat spectrin molecules.
AB  - The unfolding pathways of multiple-repeat spectrin molecules were examined using
      steered molecular dynamics (SMD) simulations to forcibly unfold double- and
      triple-repeat spectrin molecules. Although SMD has previously been used to study
      other repeating-domain proteins, spectrin offers a unique challenge in that the
      linker connecting repeat units has a definite secondary structure, that of an
      alpha-helix. Therefore, the boundary conditions imposed on a double- or triple
      repeat spectrin must be carefully considered if any relationship to the real
      system is to be deduced. This was accomplished by imposing additional forces on
      the system which ensure that the terminal alpha-helices behave as if there were
      no free noncontiguous helical ends. The results of the SMD simulations highlight
      the importance of the rupture of the alpha-helical linker on the subsequent
      unfolding events. Rupture of the linker propagates unfolding in the adjacent
      repeat units by destabilizing the tertiary structure, ultimately resulting in
      complete unfolding of the affected repeat unit. Two dominant classes of unfolding
      pathways are observed after the initial rupture of a linker which involve either
      rupture of another linker (possibly adjacent) or rupture of the basic tertiary
      structure of a repeat unit. The relationship between the force response observed
      on simulation timescales and those of experiment or physiological conditions is
      also discussed.

PMID- 16891372
TI  - Impact of the mutation A21G (Flemish variant) on Alzheimer's beta-amyloid dimers
      by molecular dynamics simulations.
AB  - Soluble oligomers of the amyloid beta-protein (Abeta) are linked to Alzheimer's
      disease. Irrespective of the nature of the nucleus before fibril growth, dimers
      are essential species in Abeta assembly, but their transient character has
      precluded, thus far, high-resolution structure determination. We have
      investigated the effects of the point mutation A21G on Abeta dimers by performing
      high temperature all-atom molecular dynamics simulations of Abeta(40), Abeta(42),
      and their Flemish variants (A21G) starting from their fibrillar conformations.
      Abeta dimers are found in equilibrium between various topologies, and the absence
      of common structural features shared by the four species makes problematic the
      design of a unique inhibitor for blocking dimers. We also show that the impact of
      the point mutation A21G on Abeta structure and dynamics varies from Abeta(40) to
      Abeta(42). Finally, we provide a possible structural explanation for the reduced
      aggregation rate of Abeta fibrils containing the Flemish disease-causing
      mutation.

PMID- 16891373
TI  - Quantitative relation between intermolecular and intramolecular binding of pro
      rich peptides to SH3 domains.
AB  - Flexible linkers are often found to tether binding sequence motifs or connect
      protein domains. Here we analyze three usages of flexible linkers: 1),
      intramolecular binding of proline-rich peptides (PRPs) to SH3 domains for kinase
      regulation; 2), intramolecular binding of PRP for increasing the folding
      stability of SH3 domains; and 3), covalent linking of PRPs and other ligands for
      high-affinity bivalent binding. The basis of these analyses is a quantitative
      relation between intermolecular and intramolecular binding constants. This
      relation has the form K(i) = K(e0)p for intramolecular binding and K(e) =
      K(e01)K(e02)p for bivalent binding. The effective concentration p depends on the
      length of the linker and the distance between the linker attachment points in the
      bound state. Several applications illustrate the usefulness of the quantitative
      relation. These include intramolecular binding to the Itk SH3 domain by an
      internal PRP and to a circular permutant of the alpha-spectrin SH3 domain by a
      designed PRP, and bivalent binding to the two SH3 domains of Grb2 by two linked
      PRPs. These and other examples suggest that flexible linkers and sequence motifs
      tethered to them, like folded protein domains, are also subject to tight control
      during evolution.

PMID- 16891374
TI  - Do protein molecules unfold in a simple shear flow?
AB  - Protein molecules typically unfold (denature) when subjected to extremes of heat,
      cold, pH, solvent composition, or mechanical stress. One might expect that
      shearing forces induced by a nonuniform fluid flow would also destabilize
      proteins, as when a protein solution flows rapidly through a narrow channel.
      However, although the protein literature contains many references to shear
      denaturation, we find little quantitative evidence for the phenomenon. We have
      investigated whether a high shear can destabilize a small globular protein to any
      measurable extent. We study a protein (horse cytochrome c, 104 amino acids) whose
      fluorescence increases sharply upon unfolding. By forcing the sample through a
      silica capillary (inner diameter 150-180 microm) at speeds approaching 10 m/s, we
      subject the protein to shear rates dv(z)/dr as large as approximately 2 x 10(5)
      s(-1) while illuminating it with an ultraviolet laser. We can readily detect
      fluorescence changes of <1%, corresponding to shifts of < approximately 0.01
      kJ/mol in the stability of the folded state. We find no evidence that even our
      highest shear rates significantly destabilize the folded protein. A simple model
      suggests that extraordinary shear rates, approximately 10(7) s(-1), would be
      required to denature typical small, globular proteins in water.

PMID- 16891376
TI  - Impact of the excision of an ancient repeat insertion on Rickettsia conorii
      guanylate kinase activity.
AB  - The genomic sequencing of Rickettsia conorii revealed a new family of Rickettsia
      specific palindromic elements (RPEs) capable of in-frame insertion in preexisting
      open reading frames (ORFs). Many of these altered ORFs correspond to proteins
      with well-characterized or essential functions in other microorganisms. Previous
      experiments indicated that RPE-containing genes are normally transcribed and that
      no excision of the repeat occurs at the mRNA level. Using mass spectrometry, we
      now confirmed the retention of the RPE-derived amino acid residues in 4 proteins
      successfully expressed in Escherichia coli, raising the general question of the
      consequences of this common insertion event on the fitness of Rickettsia enzymes.
      The predicted guanylate kinase activity of the R. conorii gmk gene product was
      measured both on the RPE-containing and RPE-excised recombinant proteins. We show
      that the 2 proteins are active but exhibit substantial differences in their
      affinity for adenosine triphosphate, guanosine monophosphate, and catalytic
      constants. The distribution of the RPEgmk insert among Rickettsia species
      indicates that the insertion event is ancient and occurred after the divergence
      of Rickettsia felis and R. conorii but before that of Rickettsia helvetica and R.
      conorii. We found no evidence that the gmk gene fixed adaptive changes to
      compensate the RPE peptide insertion. Furthermore, the analysis of the rates of
      divergence in 23 RPE-containing genes indicates that coding RPE repeats tend to
      evolve under weak selective constraint, at a rate similar to intergenic noncoding
      RPE sequences. Altogether, these results suggest that the insertion of RPE
      encoded "selfish peptides," although respecting the original fold and activity of
      the host proteins, might be slightly detrimental to the enzyme efficiency within
      limits tolerable for slow-growing intracellular parasites such as Rickettsia.

PMID- 16891377
TI  - Exploring the relationship between sequence similarity and accurate phylogenetic
      trees.
AB  - We have characterized the relationship between accurate phylogenetic
      reconstruction and sequence similarity, testing whether high levels of sequence
      similarity can consistently produce accurate evolutionary trees. We generated
      protein families with known phylogenies using a modified version of the
      PAML/EVOLVER program that produces insertions and deletions as well as
      substitutions. Protein families were evolved over a range of 100-400 point
      accepted mutations; at these distances 63% of the families shared significant
      sequence similarity. Protein families were evolved using balanced and unbalanced
      trees, with ancient or recent radiations. In families sharing statistically
      significant similarity, about 60% of multiple sequence alignments were 95%
      identical to true alignments. To compare recovered topologies with true
      topologies, we used a score that reflects the fraction of clades that were
      correctly clustered. As expected, the accuracy of the phylogenies was greatest in
      the least divergent families. About 88% of phylogenies clustered over 80% of
      clades in families that shared significant sequence similarity, using Bayesian,
      parsimony, distance, and maximum likelihood methods. However, for protein
      families with short ancient branches (ancient radiation), only 30% of the most
      divergent (but statistically significant) families produced accurate phylogenies,
      and only about 70% of the second most highly conserved families, with median
      expectation values better than 10(-60), produced accurate trees. These values
      represent upper bounds on expected tree accuracy for sequences with a simple
      divergence history; proteins from 700 Giardia families, with a similar range of
      sequence similarities but considerably more gaps, produced much less accurate
      trees. For our simulated insertions and deletions, correct multiple sequence
      alignments did not perform much better than those produced by T-COFFEE, and
      including sequences with expressed sequence tag-like sequencing errors did not
      significantly decrease phylogenetic accuracy. In general, although less-divergent
      sequence families produce more accurate trees, the likelihood of estimating an
      accurate tree is most dependent on whether radiation in the family was ancient or
      recent. Accuracy can be improved by combining genes from the same organism when
      creating species trees or by selecting protein families with the best bootstrap
      values in comprehensive studies.

PMID- 16891378
TI  - The hidden value of missing genotypes.
AB  - Robotic systems allow vast genetic data sets to be generated automatically with
      little manual input, raising questions about accuracy. To test whether errors
      occur randomly, I used the frequencies of missing genotypes in a large human data
      set to construct a population tree. Remarkably, the gaps appear to carry as
      strong a phylogenetic signal as the actual data themselves.

PMID- 16891375
TI  - Laser-guided assembly of heterotypic three-dimensional living cell microarrays.
AB  - We have assembled three-dimensional heterotypic networks of living cells in
      hydrogel without loss of viability using arrays of time-multiplexed, holographic
      optical traps. The hierarchical control of the cell positions is achieved with,
      to our knowledge, unprecedented submicron precision, resulting in arrays with an
      intercell separation <400 nm. In particular, we have assembled networks of Swiss
      3T3 fibroblasts surrounded by a ring of bacteria. We have also demonstrated the
      ability to manipulate hundreds of Pseudomonas aeruginosa simultaneously into two-
      and three-dimensional arrays with a time-averaged power <2 mW per trap. This is
      the first time to our knowledge that living cell arrays of such complexity have
      been synthesized, and it represents a milestone in synthetic biology and tissue
      engineering.

PMID- 16891379
TI  - Protein evolution is faster outside the cell.
AB  - Some proteins are highly conserved across all species, whereas others diverge
      significantly even between closely related species. Attempts have been made to
      correlate the rate of protein evolution to amino acid composition, protein
      dispensability, and the number of protein-protein interactions, but in all cases,
      conflicting studies have shown that the theories are hard to confirm
      experimentally. The only correlation that is undisputed so far is that
      highly/broadly expressed proteins seem to evolve at a lower rate. Consequently,
      it has been suggested that correlations between evolution rate and factors like
      protein dispensability or the number of protein-protein interactions could be
      just secondary effects due to differences in expression. The purpose of this
      study was to analyze mammalian proteins/genes with known subcellular location for
      variations in evolution rates. We show that proteins that are exported
      (extracellular proteins) evolve faster than proteins that reside inside the cell
      (intracellular proteins). We find weak, but significant, correlations between
      evolution rates and expression levels, percentage of tissues in which the
      proteins are expressed (expression broadness), and the number of protein
      interaction partners. More important, we show that the observed difference in
      evolution rate between extra- and intracellular proteins is largely independent
      of expression levels, expression broadness, and the number of protein-protein
      interactions. We also find that the difference is not caused by an
      overrepresentation of immunological proteins or disulfide bridge-containing
      proteins among the extracellular data set. We conclude that the subcellular
      location of a mammalian protein has a larger effect on its evolution rate than
      any of the other factors studied in this paper, including expression
      levels/patterns. We observe a difference in evolution rates between extracellular
      and intracellular proteins for a yeast data set as well and again show that it is
      completely independent of expression levels.

PMID- 16891380
TI  - More is not better in the early care of acute myocardial infarction: a
      prospective cohort analysis on administrative databases.
AB  - AIMS: To assess the outcome and costs of patients with acute myocardial
      infarction (AMI) after initial admission to hospitals with or without
      catheterization facilities in Belgium. METHODS AND RESULTS: From a nationwide
      hospital register, we retrieved the data of 34 961 patients discharged during
      1999-2001 with a principal diagnosis of AMI. They were initially admitted to
      hospitals without catheterization facilities (A), with diagnostic (B1) or
      interventional catheterization facilities (B2). Mortality has been recorded till
      the end of 2003 and re-admissions till the end of 2001. The mortality hazard
      ratio and 95% CI of 5 years mortality of A vs. B2 was 1.01 (0.97, 1.06) and of B1
      vs. B2 was 1.03 (0.98, 1.09). Re-admission rates and 95% CI for cardiovascular
      reason per 100 patient-years were 23.5 (22.7, 24.3) for A, 23.8 (22.5, 25.1) for
      B1, and 22.0 (21.2, 22.9) for B2. The mean cost in hospital of a patient at low
      risk with a single stay was in A 4072 euro (median: 3,861; IQR: 4467-3476), in B1
      5083 euro (median: 5153; IQR: 5769-4340), and in B2 7741 euro (median: 7553; IQR:
      8211-7298). CONCLUSION: Services with catheterization facilities compared with
      services without them showed no better health outcomes, but delivered more
      expensive care.

PMID- 16891381
TI  - Pre-treatment with Irbesartan attenuates left atrial stunning after electrical
      cardioversion of atrial fibrillation.
AB  - AIMS: Left atrial (LA) stunning, the transient impairment of LA function, is
      responsible for an increased thrombo-embolic risk after cardioversion of atrial
      fibrillation (AF). Angiotensin receptor blockers (ARBs) attenuate atrial
      remodelling in AF and could theoretically influence LA stunning. We studied the
      effect of Irbesartan on LA stunning. METHODS AND RESULTS: We prospectively
      assigned 50 patients from the outpatient clinic undergoing electrical
      cardioversion for AF with duration of >4 weeks, into two matched groups: 25
      patients were treated with Irbesartan (228+/-93 mg/day) for at least 2 weeks
      prior to cardioversion (Irbesartan group); 25 patients did not receive ARBs
      (control group). The groups did not differ concerning age (64+/-13 vs. 63+/-13
      years, respectively), AF duration (20+/-18 vs. 20+/-19 weeks), underlying
      disease, LA diameter (46+/-7 vs. 47+/-9 mm), left ventricular dimensions, and
      ejection fraction (47.7+/-11.6 vs. 49.7+/-14.5%). We assessed LA appendage
      emptying velocities (LAAEV) and LA spontaneous echo contrast (LASEC) by
      transoesophageal echocardiography before and after cardioversion and at 2 weeks,
      and the A-wave by transthoracic echocardiography after cardioversion, at 2 and at
      4 weeks. LA stunning was significantly attenuated in the Irbesartan group. The
      reduction of LAAEV immediately after cardioversion was significantly less in the
      Irbesartan group (LAAEV reduction of 9+/-49% from 28+/-9 cm/s before
      cardioversion to 25+/-13 cm/s immediately afterwards) than in the control group
      (reduction of 48+/-20% from 34+/-15 cm/s before cardioversion to 16+/-6 cm/s
      afterwards) (P = 0.048). New or increased LASEC occurred in eight patients (32%)
      in the Irbesartan vs. 16 patients (64%) in the control group (P = 0.046).
      CONCLUSION: Irbesartan significantly attenuates LA stunning after electrical
      cardioversion of AF. Therefore, ARBs may represent an important pharmacological
      supplementation in patients being prepared for cardioversion.

PMID- 16891382
TI  - Weight-change as a prognostic marker in 12 550 patients following acute
      myocardial infarction or with stable coronary artery disease.
AB  - AIMS: To examine the prognostic importance of weight-change in patients with
      coronary artery disease (CAD), especially following acute myocardial infarction
      (AMI). METHODS AND RESULTS: In 4360 AMI patients (OPTIMAAL trial) without
      baseline oedema, we assessed 3-month weight-change, baseline body mass index
      (BMI), demographics, patient history, medication, physical examination, and
      biochemical analyses. Weight-change was defined as change >+/-0.1 kg/baseline BMI
      unit. Patients were accordingly categorized into three groups; weight-loss,
      weight-stability, and weight-gain. Our findings were validated in 4012 AMI
      patients (CONSENSUS II trial) and 4178 stable CAD patients (79% with prior AMI,
      4S trial). Median follow-up was 2.7 years, 3 months, and 4.4 years, respectively.
      In OPTIMAAL, 3-month weight-loss (vs. weight-stability) independently predicted
      increased all-cause death [n=471; hazard ratio (HR) 1.26; 95% CI 1.01-1.56;
      P=0.039] and cardiac death (n=299, HR 1.33, 95% CI 1.02-1.73, P=0.034). Weight
      gain yielded risk similar to weight-stability (HR 1.07, P=0.592 and 0.97,
      P=0.866, respectively). In CONSENSUS II, 3-month weight-loss independently
      predicted increased mortality (HR 3.87, P=0.008). Weight-gain yielded risk
      similar to weight-stability (HR 1.11, P=0.860). In 4S, 1-year weight-loss
      independently predicted increased mortality (HR 1.44, P=0.004). Weight-gain
      conferred risk similar to weight-stability (HR 1.05, P=0.735). CONCLUSION: In
      patients following AMI or with stable CAD, weight-loss but not weight-gain was
      independently associated with increased mortality risk.

PMID- 16891383
TI  - Actions anchored by concepts: defective action comprehension in semantic
      dementia.
AB  - OBJECTIVE: To study the ability of patients with semantic dementia to understand
      actions, in order to examine the contribution of semantic memory to action
      comprehension. METHODS: The ability to comprehend symbolic and instrumental
      actions was assessed in 6 patients with semantic dementia and 10 healthy
      controls. The patients were also given the imitation test of meaningful and
      meaningless actions. RESULTS: In all patients with semantic dementia,
      comprehension of both symbolic and instrumental actions was defective. The
      comprehension of symbolic actions was more impaired than that of instrumental
      actions. Their ability to imitate other's actions was well preserved. CONCLUSION:
      This study showed that comprehension of action was impaired in semantic dementia,
      suggesting that semantic memory has an important role in comprehension of human
      action.

PMID- 16891384
TI  - Moderate therapeutic efficacy of positron emission tomography-navigated
      repetitive transcranial magnetic stimulation for chronic tinnitus: a randomised,
      controlled pilot study.
AB  - BACKGROUND: Tinnitus has been shown to respond to modulations of cortical
      activity by high-frequency and low-frequency repetitive transcranial magnetic
      stimulation (rTMS). OBJECTIVE: To determine the tinnitus-attenuating effects of a
      2-week daily regimen of rTMS, navigated to the maximum of tinnitus-related
      increase in regional cerebral blood flow. METHODS: Six patients with chronic
      tinnitus were enrolled in this sham-controlled crossover study and treated with
      2x2 weeks of suprathreshold 1 Hz rTMS (30 min) applied to the region with maximal
      tinnitus-related increase in regional cerebral blood flow delineated by
      functional imaging with [15O]H2O positron emission tomography and a control area.
      Tinnitus-related distress was assessed before and after each treatment and 2
      weeks after the end of the 4-week course of stimulation using a validated
      tinnitus questionnaire. Additional self-assessment scores of tinnitus change,
      loudness and annoyance were obtained. RESULTS: In five of six patients, rTMS
      induced greater reduction of the tinnitus questionnaire score than sham
      stimulation. In two patients, all parameters measured (tinnitus change score,
      tinnitus loudness, tinnitus annoyance) showed unequivocal improvement. At the
      group level, the degree of response in the tinnitus questionnaire score was
      correlated with tinnitus-associated activation of the anterior cingulate cortex.
      Two weeks after the final stimulation, tinnitus had returned to baseline in all
      patients but one. CONCLUSION: Tinnitus can be attenuated by low-frequency rTMS
      navigated to each person's maximum tinnitus-related cortical hyperactivity. The
      effects are only moderate; interindividual responsiveness varies and the
      attenuation seems to wear off within 2 weeks after the last stimulation session.
      Notably, tinnitus-related anterior cingulate cortex activation seems to predict
      the response to rTMS treatment.

PMID- 16891385
TI  - Magnetoencephalographic spike sources associated with auditory auras in
      paediatric localisation-related epilepsy.
AB  - OBJECTIVE: To characterise magnetoencephalographic spike sources in paediatric
      patients with auditory auras and recurrent localisation-related epilepsy.
      METHODS: Six patients (four boys and two girls (ages 7-14 years) were
      retrospectively studied. All patients had auditory auras as part of their initial
      seizure manifestation, including four patients who underwent previous brain
      surgery. Scalp video electroencephalography and magnetoencephalography (MEG) were
      carried out in six patients, intraoperative electrocorticography in three
      patients and extraoperative intracranial video electroencephalography in one
      patient. MEG auditory-evoked fields (AEFs) were studied in four patients.
      RESULTS: Three patients had elementary auditory auras, one had complex auditory
      aura and two had both complex and elementary auras. All six patients had
      clustered MEG spike sources with coexisting scattered spike sources. MEG clusters
      were localised in the superior temporal gyrus with surrounding scatters in four
      patients (two left and two right); two patients had scattered spikes in the
      superior temporal gyrus in addition to clustered MEG spike sources in the left
      inferior and middle frontal gyri or parieto-occipital region. AEFs were located
      within an MEG cluster in one patient and within 3 cm of a cluster in two
      patients. Surgical resection, including the regions of MEG clusters, was carried
      out in four patients. Three of four patients who had previous surgeries were
      seizure free at 2 years after excision of the MEG cluster region. CONCLUSIONS:
      MEG spike sources clustered in the superior temporal gyrus in six patients with
      auditory auras. These spike sources were in close proximity or seemed to engulf
      the magnetic AEF. Areas with MEG spike sources contained the residual or
      recurrent epileptogenic zone after incomplete cortical excision for lesional
      epilepsy.

PMID- 16891386
TI  - Medial temporal atrophy but not memory deficit predicts progression to dementia
      in patients with mild cognitive impairment.
AB  - BACKGROUND: The diagnosis of mild cognitive impairment (MCI) is clinically
      unhelpful, as many patients with MCI develop dementia but many do not. OBJECTIVE:
      To identify clinical instruments easily applicable in the clinical routine that
      might be useful to predict progression to dementia in patients with MCI assessed
      in the outpatient facility of a memory clinic. PARTICIPANTS AND METHODS: 52
      dementia-free patients (mean (standard deviation) age 70 (6) years; 56% women)
      with MCI, and 65 healthy controls (age 69 (6) years; 54% women) underwent brain
      magnetic resonance scan with standardised visual assessment of medial temporal
      atrophy (MTA) and subcortical cerebrovascular lesions (SVLs). Follow-up
      assessment occurred 15.4 (SD 3.4) months after baseline to detect incident
      dementia and improvement, defined as normal neuropsychological performance on
      follow-up. RESULTS: Patients were classified into three groups according to the
      presence of memory disturbance only (MCI Mem), other neuropsychological deficits
      (MCI Oth) or both (MCI Mem+). MCI Mem and Mem+ showed MTA more frequently (31%
      and 47% v 5% and 14% of controls and MCI Oth, p<0.001). 11 patients developed
      dementia (annual rate 16.5%) and 7 improved on follow-up. The only independent
      predictor of progression was MTA (odds ratio (OR) 7.1, 95% confidence interval
      (CI) 1.4 to 35.0), whereas predictors of improvement were the absence of memory
      impairment (OR 18.5, 95% CI 2.0 to 171.3) and normal MRI scan (OR 10.0, 95% CI
      1.7 to 60.2). CONCLUSION: Neuropsychological patterns identify groups of patients
      with MCI showing specific clinical features and risk of progression to dementia.
      MTA clinically rated with a visual scale is the most relevant predictor of
      progression and improvement.

PMID- 16891387
TI  - Modeling the effect of stretch and plasma membrane tension on Na+-K+-ATPase
      activity in alveolar epithelial cells.
AB  - While a number of whole cell mechanical models have been proposed, few, if any,
      have focused on the relationship among plasma membrane tension, plasma membrane
      unfolding, and plasma membrane expansion and relaxation via lipid insertion. The
      goal of this communication is to develop such a model to better understand how
      plasma membrane tension, which we propose stimulates Na(+)-K(+)-ATPase activity
      but possibly also causes cell injury, may be generated in alveolar epithelial
      cells during mechanical ventilation. Assuming basic relationships between plasma
      membrane unfolding and tension and lipid insertion as the result of tension, we
      have captured plasma membrane mechanical responses observed in alveolar
      epithelial cells: fast deformation during fast cyclic stretch, slower, time
      dependent deformation via lipid insertion during tonic stretch, and cell recovery
      after release from stretch. The model estimates plasma membrane tension and
      predicts Na(+)-K(+)-ATPase activation for a specified cell deformation time
      course. Model parameters were fit to plasma membrane tension, whole cell
      capacitance, and plasma membrane area data collected from the literature for
      osmotically swollen and shrunken cells. Predictions of membrane tension and
      stretch-stimulated Na(+)-K(+)-ATPase activity were validated with measurements
      from previous studies. As a proof of concept, we demonstrate experimentally that
      tonic stretch and consequent plasma membrane recruitment can be exploited to
      condition cells against subsequent cyclic stretch and hence mitigate stretch
      induced responses, including stretch-induced cell death and stretch-induced
      modulation of Na(+)-K(+)-ATPase activity. Finally, the model was exercised to
      evaluate plasma membrane tension and potential Na(+)-K(+)-ATPase stimulation for
      an assortment of traditional and novel ventilation techniques.

PMID- 16891388
TI  - Regulation of ENaC and CFTR expression with K+ channel modulators and effect on
      fluid absorption across alveolar epithelial cells.
AB  - In a recent study (Leroy C, Dagenais A, Berthiaume Y, and Brochiero E. Am J
      Physiol Lung Cell Mol Physiol 286: L1027-L1037, 2004), we identified an ATP
      sensitive K(+) (K(ATP)) channel in alveolar epithelial cells, formed by inwardly
      rectifying K(+) channel Kir6.1/sulfonylurea receptor (SUR)2B subunits. We found
      that short applications of K(ATP), voltage-dependent K(+) channel KvLQT1, and
      calcium-activated K(+) (K(Ca)) channel modulators modified Na(+) and Cl(-)
      currents in alveolar monolayers. In addition, it was shown previously that a
      K(ATP) opener increased alveolar liquid clearance in human lungs by a mechanism
      possibly related to epithelial sodium channels (ENaC). We therefore hypothesized
      that prolonged treatment with K(+) channel modulators could induce a sustained
      regulation of ENaC activity and/or expression. Alveolar monolayers were treated
      for 24 h with inhibitors of K(ATP), KvLQT1, and K(Ca) channels identified by PCR.
      Glibenclamide and clofilium (K(ATP) and KvLQT1 inhibitors) strongly reduced basal
      transepithelial current, amiloride-sensitive Na(+) current, and forskolin
      activated Cl(-) currents, whereas pinacidil, a K(ATP) activator, increased them.
      Interestingly, K(+) inhibitors or membrane depolarization (induced by valinomycin
      in high-K(+) medium) decreased alpha-, beta-, and gamma-ENaC and CFTR mRNA. alpha
      ENaC and CFTR proteins also declined after glibenclamide or clofilium treatment.
      Conversely, pinacidil augmented ENaC and CFTR mRNAs and proteins. Since alveolar
      fluid transport was found to be driven, at least in part, by Na(+) transport
      through ENaC, we tested the impact of K(+) channel modulators on fluid absorption
      across alveolar monolayers. We found that glibenclamide and clofilium reduced
      fluid absorption to a level similar to that seen in the presence of amiloride,
      whereas pinacidil slightly enhanced it. Long-term regulation of ENaC and CFTR
      expression by K(+) channel activity could benefit patients with pulmonary
      diseases affecting ion transport and fluid clearance.

PMID- 16891389
TI  - Extravascular lung water measurements and hemodynamic monitoring in the
      critically ill: bedside alternatives to the pulmonary artery catheter.
AB  - The recently completed Fluid and Catheter Treatment Trial conducted by the
      National Institutes of Health ARDSNetwork casts doubt on the value of routine
      pulmonary artery catheterization for hemodynamic management of the critically
      ill. Several alternatives are available, and, in this review, we evaluate the
      theoretical, validation, and empirical databases for two of these: transpulmonary
      thermodilution measurements (yielding estimates of cardiac output, intrathoracic
      blood volume, and extravascular lung water) that do not require a pulmonary
      artery catheter, and hemodynamic measurements (including estimates of cardiac
      output and ejection time, a variable sensitive to intravascular volume) obtained
      by esophageal Doppler analysis of blood flow through the descending aorta. We
      conclude that both deserve serious consideration as a means of acquiring useful
      hemodynamic data for managing shock and fluid resuscitation in the critically
      ill, especially in those with acute lung injury and pulmonary edema, but that
      additional study, including carefully performed, prospective clinical trials
      demonstrating outcome benefit, is needed.

PMID- 16891390
TI  - p38 MAPK activation coupled to endocytosis is a determinant of endothelial
      monolayer integrity.
AB  - We show in rat lung microvessel endothelial cells (RLMVEC) that endocytosis is a
      critical determinant of activation of mitogen-activated protein kinase (MAPK) and
      thereby regulates endothelial monolayer integrity. In RLMVEC grown in serum-free
      medium, we observed that albumin supplementation induced the phosphorylation of
      p38 MAPK within 30 min, which persisted for up to 2 h. Engagement of the
      endocytic machinery regulated the activation of p38 MAPK that contributed to
      endothelial cell proliferation and reduction of apoptosis. We also observed an
      interaction between the caveolar protein caveolin-1 and p38 MAPK with reciprocal
      coimmunoprecipitation assays and colocalization using double-label
      immunofluorescence staining. Knockdown of caveolin-1 expression with small
      interfering RNA significantly reduced endocytosis and activation of p38 MAPK and
      interfered with the ability of endothelial cells to form a confluent monolayer.
      Thus caveolae-mediated endocytosis and concomitant activation of p38 MAPK may
      help to maintain endothelial monolayer integrity by signaling proliferation and
      survival of endothelial cells.

PMID- 16891391
TI  - CD38-deficient mice have reduced airway hyperresponsiveness following IL-13
      challenge.
AB  - The transmembrane glycoprotein CD38 in airway smooth muscle is the source of
      cyclic-ADP ribose, an intracellular calcium-releasing molecule, and is subject to
      regulatory effects of cytokines such as interleukin (IL)-13, a cytokine
      implicated in asthma. We investigated the role of CD38 in airway
      hyperresponsiveness using a mouse model of IL-13-induced airway disease. Wild
      type (WT) and CD38-deficient (CD38KO) mice were intranasally challenged with 5
      microg of IL-13 three times on alternate days under isoflurane anesthesia. Lung
      resistance (R(L)) in response to inhaled methacholine was measured 24 h after the
      last challenge in pentobarbital-anesthetized, tracheostomized, and mechanically
      ventilated mice. Bronchoalveolar cytokines, bronchoalveolar and parenchymal
      inflammation, and smooth muscle contractility and relaxation using tracheal
      segments were also evaluated. Changes in methacholine-induced R(L) were
      significantly greater in the WT than in the CD38KO mice following intranasal IL
      13 challenges. Airway reactivity after IL-13 exposure, as measured by the slope
      of the methacholine dose-response curve, was significantly higher in the WT than
      in the CD38KO mice. The rate of isometric force generation in tracheal segments
      (e.g., smooth muscle reactivity) was greater in the WT than in the CD38KO mice
      following incubation with IL-13. IL-13 treatment reduced isoproterenol-induced
      relaxations to similar magnitudes in tracheal segments obtained from WT and
      CD38KO mice. Both WT and CD38KO mice developed significant bronchoalveolar and
      parenchymal inflammation after IL-13 challenges compared with naive controls. The
      results indicate that CD38 contributes to airway hyperresponsiveness in lungs
      exposed to IL-13 at least partly by increasing airway smooth muscle reactivity to
      contractile agonists.

PMID- 16891392
TI  - Hypoxia-induced mitogenic factor has proangiogenic and proinflammatory effects in
      the lung via VEGF and VEGF receptor-2.
AB  - From a mouse model of hypoxia-induced pulmonary hypertension, we previously found
      a highly upregulated protein in the lung that we named hypoxia-induced mitogenic
      factor (HIMF), also known as found in inflammatory zone 1 (FIZZ1), and resistin
      like molecule alpha (RELMalpha). However, the mechanisms of HIMF in the pulmonary
      vascular remodeling remain unknown. We now demonstrate that HIMF promoted cell
      proliferation, migration, and the production of vascular endothelial growth
      factor (VEGF) and monocyte chemotactic protein-1 (MCP-1) in pulmonary endothelial
      cells as well as the production of reactive oxygen species in murine
      monocyte/macrophage cells. HIMF-induced CD31-positive cell infiltrate in in vivo
      Matrigel plugs was significantly suppressed by VEGF receptor-2 (VEGFR2) blockade.
      In ex vivo studies, HIMF stimulated the production of VEGF, MCP-1, and stromal
      cell-derived factor-1 (SDF-1) in the lung resident cells, and VEGFR2
      neutralization significantly suppressed HIMF-induced MCP-1 and SDF-1 production.
      Furthermore, intravenous injection of HIMF showed marked increase of CD68
      positive inflammatory cells in the lungs, and these events were attenuated by
      VEGFR2 neutralization. Intravenous injection of HIMF also downregulated the
      expression of VEGFR2 in the lung. These results suggest that HIMF plays critical
      roles in pulmonary inflammation as well as angiogenesis.

PMID- 16891393
TI  - TNF-alpha increases tyrosine phosphorylation of vascular endothelial cadherin and
      opens the paracellular pathway through fyn activation in human lung endothelia.
AB  - Tumor necrosis factor (TNF)-alpha is a key mediator of sepsis-associated
      multiorgan failure, including the acute respiratory distress syndrome. We
      examined the role of protein tyrosine phosphorylation in TNF-alpha-induced
      pulmonary vascular permeability. Postconfluent human lung microvascular and
      pulmonary artery endothelial cell (EC) monolayers exposed to human recombinant
      TNF-alpha displayed a dose- and time-dependent increase in transendothelial
      [(14)C]albumin flux in the absence of EC injury. TNF-alpha also increased
      tyrosine phosphorylation of EC proteins, and several substrates were identified
      as the zonula adherens proteins vascular endothelial (VE)-cadherin, and beta
      catenin, gamma-catenin, and p120 catenin (p120(ctn)). Prior protein tyrosine
      kinase (PTK) inhibition protected against the TNF-alpha effect. TNF-alpha
      activated multiple PTKs, including src family PTKs. Prior PTK inhibition with the
      src-selective agents PP1 and PP2 each protected against approximately 60% of the
      TNF-alpha-induced increment in [(14)C]albumin flux. PP2 also blocked TNF-alpha
      induced tyrosine phosphorylation of VE-cadherin, gamma-catenin, and p120(ctn). To
      identify which src family kinase(s) was required for TNF-alpha-induced vascular
      permeability, small interfering RNA (siRNA) targeting each of the three src
      family PTKs expressed in human EC, c-src, fyn, and yes, were introduced into the
      barrier function assay. Only fyn siRNA protected against the TNF-alpha effect,
      whereas the c-src and yes siRNAs did not. These combined data suggest that TNF
      alpha regulates the pulmonary vascular endothelial paracellular pathway, in part,
      through fyn activation.

PMID- 16891394
TI  - Contribution of T cell subsets to the pathophysiology of Pneumocystis-related
      immunorestitution disease.
AB  - Immune-mediated lung injury is an important component of Pneumocystis pneumonia
      (PcP)-related immunorestitution disease (IRD). However, the individual
      contribution of CD4(+) and CD8(+) T cells to the pathophysiology of IRD remains
      undetermined. Therefore, IRD was modeled in severe combined immunodeficient mice,
      and specific T cell depletion was used to determine how T cell subsets interact
      to affect the nature and severity of disease. CD4(+) cells were more abundant
      than CD8(+) cells during the acute stage of IRD that coincided with impaired
      pulmonary physiology and organism clearance. Conversely, CD8(+) cells were more
      abundant during the resolution phase following P. carinii clearance. Depletion of
      CD4(+) T cells protected mice from the acute pathophysiology of IRD. However,
      these mice could not clear the infection and developed severe PcP at later time
      points when a pathological CD8(+) T cell response was observed. In contrast, mice
      depleted of CD8(+) T cells efficiently cleared the infection but developed more
      severe disease, an increased frequency of IFN-gamma-producing CD4(+) cells, and a
      prolonged CD4(+) T cell response than mice with both CD4(+) and CD8(+) cells.
      These data suggest that CD4(+) T cells mediate the acute respiratory disease
      associated with IRD. In contrast, CD8(+) T cells contributed to neither lung
      injury nor organism clearance when CD4(+) cells were present, but instead served
      to modulate CD4 function. In the absence of CD4(+) cells, CD8(+) T cells produced
      a nonprotective, pathological immune response. These data suggest that the
      interplay of CD4(+) and CD8(+) T cells affects the ultimate outcome of PcP
      related IRD.

PMID- 16891396
TI  - Ras association domain family 1C protein stimulates human lung cancer cell
      proliferation.
AB  - Recently, the Ras association domain family 1 gene (RASSF1) has been identified
      as a Ras effector encoding two major mRNA forms, RASSF1A and RASSF1C, derived by
      alternative promoter selection and alternative mRNA splicing. RASSF1A is a tumor
      suppressor gene. However, the function of RASSF1C, both in normal and cancer
      cells, is still unknown. To learn more about the function of RASSF1C in human
      cancer cells, we tested the effect of silencing RASSF1C mRNA with small
      interfering RNA on lung cancer cells (NCI H1299) that express RASSF1C but not
      RASSF1A. Small interfering RNA specific for RASSF1C reduced RASSF1C mRNA levels
      compared with controls. This reduction in RASSF1C expression caused a significant
      decrease in lung cancer cell proliferation. Furthermore, overexpression of
      RASSF1C increased cell proliferation in lung cancer cells. Finally, we found that
      RASSF1C, unlike RASSF1A, does not upregulate N-cadherin 2 and transglutaminase 2
      protein expression in NCI H1299 lung cancer cells. This suggests that RASSF1C and
      RASSF1A have different effector targets. Together, our findings suggest that
      RASSF1C, unlike RASSF1A, is not a tumor suppressor but rather stimulates lung
      cancer cell proliferation.

PMID- 16891397
TI  - Epithelial-derived TGF-beta2 modulates basal and wound-healing subepithelial
      matrix homeostasis.
AB  - The epithelium influences the mesenchyme during dynamic processes such as
      embryogenesis, wound healing, fibrosis, and carcinogenesis. Since transforming
      growth factor-beta (TGF-beta) modulates these processes, we hypothesized that
      epithelial-derived TGF-beta also plays a critical role in maintaining the
      extracellular matrix at basal conditions. We utilized an in vitro model of the
      epithelial-mesenchymal trophic unit in the human airways to determine the role of
      epithelial-derived TGF-beta in modulating the extracellular matrix under basal
      and wound-healing conditions. When differentiated at an air-liquid interface, the
      human bronchial epithelium produces active TGF-beta2 at a concentration of 50-70
      pg/ml, whereas TGF-beta1 is undetectable. TGF-beta2 increases two- to threefold
      following scrape injury in a dose-dependent fashion and significantly enhances
      both alpha-smooth muscle actin expression in the underlying collagen-embedded
      fibroblasts and secretion of tenascin-C into the matrix. Multiphoton microscopy
      demonstrates substantially enhanced second harmonic generation from fibrillar
      collagen in the matrix. Pretreatment of the matrix with either sirolimus (2.5 nM)
      or paclitaxel (10 nM) abolishes the increases in both TGF-beta2 and second
      harmonic generation in response to epithelial injury. In the absence of the
      epithelium, exogenous active TGF-beta2 (0-400 pg/ml) produces a biphasic response
      in the second harmonic signal with a minimum occurring at the epithelial-derived
      basal level. We conclude that epithelial-derived TGF-beta2 is secreted in
      response to injury, significantly alters the bulk optical properties of the
      extracellular matrix, and its tight regulation may be required for normal
      collagen homeostasis.

PMID- 16891395
TI  - Analysis of methylarginine metabolism in the cardiovascular system identifies the
      lung as a major source of ADMA.
AB  - Protein arginine methylation is catalyzed by a family of enzymes called protein
      arginine methyltransferases (PRMTs). Three forms of methylarginine have been
      identified in eukaryotes: monomethylarginine (l-NMMA), asymmetric
      dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA), all characterized
      by methylation of one or both guanidine nitrogen atoms of arginine. l-NMMA and
      ADMA, but not SDMA, are competitive inhibitors of all nitric oxide synthase
      isoforms. SDMA is eliminated almost entirely by renal excretion, whereas l-NMMA
      and ADMA are further metabolized by dimethylarginine dimethylaminohydrolase
      (DDAH). To explore the interplay between methylarginine synthesis and degradation
      in vivo, we determined PRMT expression and DDAH activity in mouse lung, heart,
      liver, and kidney homogenates. In addition, we employed HPLC-based quantification
      of protein-incorporated and free methylarginine, combined with immunoblotting for
      the assessment of tissue-specific patterns of arginine methylation. The salient
      findings of the present investigation can be summarized as follows: 1) pulmonary
      expression of type I PRMTs was correlated with enhanced protein arginine
      methylation; 2) pulmonary ADMA degradation was undertaken by DDAH1; 3)
      bronchoalveolar lavage fluid and serum exhibited almost identical ADMA/SDMA
      ratios, and 4) kidney and liver provide complementary routes for clearance and
      metabolic conversion of circulating ADMA. Together, these observations suggest
      that methylarginine metabolism by the pulmonary system significantly contributes
      to circulating ADMA and SDMA levels.

PMID- 16891398
TI  - Galectin-1 in secondary alveolar septae of neonatal mouse lung.
AB  - In mice, alveolarization occurs during postnatal days 4 through 12, when
      secondary alveolar septae create thin-walled alveoli in the distal lung. We
      hypothesized that genes predominantly expressed in newly forming secondary
      alveolar septae influence the process of alveolarization. To address this
      hypothesis, tips of secondary alveolar septae were isolated from sections of
      postnatal day 6 mouse lung tissue using laser capture microdissection. Total RNA
      was isolated and amplified from the dissected alveolar septal tips and from
      intact postnatal day 6 lung tissue. Gene expression in the samples was
      characterized using Affymetrix mouse U74AN2 GeneChips. Galectin-1 was an
      abundantly expressed transcript that was enriched in the alveolar septal tips
      compared with levels in the whole lung tissue. Galectins are beta-galactoside
      binding proteins involved in the regulation of cell proliferation,
      differentiation, and apoptosis in fibroblasts, muscle cells and endothelial
      cells, cell types that are present in the alveolar wall. Immunostaining in
      postnatal day 6 lung tissue confirmed that galectin-1 protein is concentrated in
      the tips of secondary alveolar septae, predominantly in myofibroblasts.
      Fibroblasts isolated from day 6 neonatal mouse lung tissue contained galectin-1
      protein. Real-time PCR demonstrated that galectin-1 mRNA levels in mouse lung
      tissue peak at postnatal day 6. Immunoblot analysis confirmed that peak levels of
      lung galectin-1 protein are found at postnatal days 6 to 12. The increased
      expression of galectin-1 at the site and time of ongoing alveolarization in the
      newborn mouse is suggestive that galectin-1 may play an important role in this
      critical aspect of lung development.

PMID- 16891399
TI  - GM-CSF and the impaired pulmonary innate immune response following hyperoxic
      stress.
AB  - We have previously demonstrated that mice exposed to sublethal hyperoxia (an
      atmosphere of >95% oxygen for 4 days, followed by return to room air) have
      significantly impaired pulmonary innate immune response. Alveolar macrophages
      (AM) from hyperoxia-exposed mice exhibit significantly diminished antimicrobial
      activity and markedly reduced production of inflammatory cytokines in response to
      stimulation with LPS compared with AM from control mice in normoxia. As a
      consequence of these defects, mice exposed to sublethal hyperoxia are more
      susceptible to lethal pneumonia with Klebsiella pneumoniae than control mice.
      Granulocyte/macrophage colony-stimulating factor (GM-CSF) is a growth factor
      produced by normal pulmonary alveolar epithelial cells that is critically
      involved in maintenance of normal AM function. We now report that sublethal
      hyperoxia in vivo leads to greatly reduced alveolar epithelial cell GM-CSF
      expression. Systemic treatment of mice with recombinant murine GM-CSF during
      hyperoxia exposure preserved AM function, as indicated by cell surface Toll-like
      receptor 4 expression and by inflammatory cytokine secretion following
      stimulation with LPS ex vivo. Treatment of hyperoxic mice with GM-CSF
      significantly reduced lung bacterial burden following intratracheal inoculation
      with K. pneumoniae, returning lung bacterial colony-forming units to the level of
      normoxic controls. These data point to a critical role for continuous GM-CSF
      activity in the lung in maintenance of normal AM function and demonstrate that
      lung injury due to hyperoxic stress results in significant impairment in
      pulmonary innate immunity through suppression of alveolar epithelial cell GM-CSF
      expression.

PMID- 16891400
TI  - Tic21 is an essential translocon component for protein translocation across the
      chloroplast inner envelope membrane.
AB  - An Arabidopsis thaliana mutant defective in chloroplast protein import was
      isolated and the mutant locus, cia5, identified by map-based cloning. CIA5 is a
      21-kD integral membrane protein in the chloroplast inner envelope membrane with
      four predicted transmembrane domains, similar to another potential chloroplast
      inner membrane protein-conducting channel, At Tic20, and the mitochondrial inner
      membrane counterparts Tim17, Tim22, and Tim23. cia5 null mutants were albino and
      accumulated unprocessed precursor proteins. cia5 mutant chloroplasts were normal
      in targeting and binding of precursors to the chloroplast surface but were
      defective in protein translocation across the inner envelope membrane. Expression
      levels of CIA5 were comparable to those of major translocon components, such as
      At Tic110 and At Toc75, except during germination, at which stage At Tic20 was
      expressed at its highest level. A double mutant of cia5 At tic20-I had the same
      phenotype as the At tic20-I single mutant, suggesting that CIA5 and At Tic20
      function similarly in chloroplast biogenesis, with At Tic20 functioning earlier
      in development. We renamed CIA5 as Arabidopsis Tic21 (At Tic21) and propose that
      it functions as part of the inner membrane protein-conducting channel and may be
      more important for later stages of leaf development.

PMID- 16891401
TI  - Functional profiling reveals that only a small number of phytochrome-regulated
      early-response genes in Arabidopsis are necessary for optimal deetiolation.
AB  - In previous time-resolved microarray-based expression profiling, we identified 32
      genes encoding putative transcription factors, signaling components, and unknown
      proteins that are rapidly and robustly induced by phytochrome (phy)-mediated
      light signals. Postulating that they are the most likely to be direct targets of
      phy signaling and to function in the primary phy regulatory circuitry, we
      examined the impact of targeted mutations in these genes on the phy-induced
      seedling deetiolation process in Arabidopsis thaliana. Using light-imposed
      concomitant inhibition of hypocotyl and stimulation of cotyledon growth as
      diagnostic criteria for normal deetiolation, we identified three major mutant
      response categories. Seven (22%) lines displayed statistically significant,
      reciprocal, aberrant photoresponsiveness in the two organs, suggesting disruption
      of normal deetiolation; 13 (41%) lines displayed significant defects either
      unidirectionally in both organs or in hypocotyls only, suggesting global effects
      not directly related to photomorphogenic signaling; and 12 (37%) lines displayed
      no significant difference in photoresponsiveness from the wild type. Potential
      reasons for the high proportion of rapidly light-responsive genes apparently
      unnecessary for the deetiolation phenotype are discussed. One of the seven
      disrupted genes displaying a significant mutant phenotype, the basic helix-loop
      helix factor-encoding PHYTOCHROME-INTERACTING FACTOR3-LIKE1 gene, was found to be
      necessary for rapid light-induced expression of the photomorphogenesis- and
      circadian-related PSEUDO-RESPONSE REGULATOR9 gene, indicating a regulatory
      function in the early phy-induced transcriptional network.

PMID- 16891402
TI  - Rice NTRC is a high-efficiency redox system for chloroplast protection against
      oxidative damage.
AB  - One of the mechanisms plants have developed for chloroplast protection against
      oxidative damage involves a 2-Cys peroxiredoxin, which has been proposed to be
      reduced by ferredoxin and plastid thioredoxins, Trx x and CDSP32, the FTR/Trx
      pathway. We show that rice (Oryza sativa) chloroplast NADPH THIOREDOXIN REDUCTASE
      (NTRC), with a thioredoxin domain, uses NADPH to reduce the chloroplast 2-Cys
      peroxiredoxin BAS1, which then reduces hydrogen peroxide. The presence of both
      NTR and Trx-like domains in a single polypeptide is absolutely required for the
      high catalytic efficiency of NTRC. An Arabidopsis thaliana knockout mutant for
      NTRC shows irregular mesophyll cell shape, abnormal chloroplast structure, and
      unbalanced BAS1 redox state, resulting in impaired photosynthesis rate under low
      light. Constitutive expression of wild-type NTRC in mutant transgenic lines
      rescued this phenotype. Moreover, prolonged darkness followed by light/dark
      incubation produced an increase in hydrogen peroxide and lipid peroxidation in
      leaves and accelerated senescence of NTRC-deficient plants. We propose that NTRC
      constitutes an alternative system for chloroplast protection against oxidative
      damage, using NADPH as the source of reducing power. Since no light-driven
      reduced ferredoxin is produced at night, the NTRC-BAS1 pathway may be a key
      detoxification system during darkness, with NADPH produced by the oxidative
      pentose phosphate pathway as the source of reducing power.

PMID- 16891403
TI  - Short-term cardiac memory and mother rotor fibrillation.
AB  - Short-term cardiac memory refers to the effects of pacing history on action
      potential duration (APD). Although the ionic mechanisms for short-term memory
      occurring over many heartbeats (also called APD accommodation) are poorly
      understood, they may have important effects on reentry and fibrillation. To
      explore this issue, we incorporated a generic memory current into the Phase I Luo
      and Rudy action potential model, which lacks short-term memory. The properties of
      this current were matched to simulate quantitatively human ventricular monophasic
      action potential accommodation. We show that, theoretically, short-term memory
      can resolve the paradox of how mother rotor fibrillation is initiated in
      heterogeneous tissue by physiological pacing. In simulated heterogeneous two
      dimensional tissue and three-dimensional ventricles containing an inward
      rectifier K(+) current gradient, short-term memory could spontaneously convert
      multiple wavelet fibrillation to mother rotor fibrillation or to a mixture of
      both fibrillation types. This was due to progressive acceleration and
      stabilization of rotors as accumulation of memory shortened APD and flattened APD
      restitution slope nonuniformly throughout the tissue.

PMID- 16891405
TI  - Reduced susceptibility to ventricular tachyarrhythmias in rats selectively bred
      for high aerobic capacity.
AB  - Reperfusion after a brief period of cardiac ischemia can lead to potentially
      lethal arrhythmias. Human epidemiological studies and experimental work with
      animals indicate that regular physical activity is associated with reductions in
      cardiovascular disease (CVD) risk factors and sudden cardiac death. Similarly,
      artificial selection of rats for high aerobic treadmill-running capacity (high
      capacity runners; HCR) has been shown to reduce CVD risk factors relative to rats
      selected as low-capacity runners (LCR). Therefore, we tested the hypothesis that
      HCR, relative to LCR rats, would be less susceptible to ischemia-reperfusion
      mediated ventricular tachyarrhythmias. To test this hypothesis, we measured the
      susceptibility to ventricular tachyarrhythmias produced by 3 min of occlusion and
      reperfusion of the left main coronary artery in conscious LCR and HCR rats.
      Results document a significantly lower incidence of ventricular tachyarrhythmias
      in HCR (3 of 11, 27.3%) relative to LCR (6 of 7, 85.6%) rats. The decreased
      susceptibility to tachyarrhythmias in HCR rats was associated with a reduced
      cardiac metabolic demand during ischemia (lower rate-pressure product and ST
      segment elevation) as well as a wider range for the autonomic control of heart
      rate. The HCR and LCR represent a unique substrate for evaluation of the
      mechanisms underlying ischemia-mediated cardiac arrhythmogenesis.

PMID- 16891406
TI  - Frequency-based analysis of the early rapid filling pressure-flow relation
      elucidates diastolic efficiency mechanisms.
AB  - Stiffness- and relaxation-based diastolic function (DF) assessment can
      characterize the presence, severity, and mechanism of dysfunction. Although
      frequency-based characterization of arterial function is routine (input
      impedance, characteristic impedance, arterial wave reflection), DF assessment via
      frequency-based methods incorporating optimization/efficiency criteria is
      lacking. By definition, optimal filling maximizes (E wave) volume and minimizes
      "loss" at constant stored elastic strain energy (which initiates mechanical,
      recoil-driven filling). In thermodynamic terms, optimal filling delivers all
      oscillatory power (rate of work) at the lowest harmonic. To assess early rapid
      filling optimization, simultaneous micromanometric left ventricular pressure and
      echocardiographic transmitral flow (Doppler E wave) were Fourier analyzed in 31
      subjects. A validated kinematic filling model provided closed-form expressions
      for E wave contours and model parameters. Relaxation-based DF impairment is
      indicated by prolonged E wave deceleration time (DT). Optimization was assessed
      via regression between the dimensionless ratio of 2nd (Q2) and 3rd flow harmonics
      (Q3) to the lowest harmonic (Q1), i.e., (Q2/Q1) or (Q3/Q1) vs. DT or c, the
      filling model's viscosity/damping (energy loss) parameter. Results show that DT
      prolongation or increased c generated increased oscillatory power at higher
      harmonics (Q2/Q1 = 0.00091DT + 0.09837, r = 0.70; Q3/Q1 = 0.00053DT + 0.02747, r
      = 0.60; Q2/Q1 = 0.00614c + 0.15527, r = 0.91; Q3/Q1 = 0.00396c + 0.05373, r =
      0.87). Because ideal filling is achieved when all oscillatory power is delivered
      at the lowest harmonic, the observed increase in power at higher harmonics is a
      measure of filling inefficiency. We conclude that frequency-based analysis
      facilitates assessment of filling efficiency and elucidates the mechanism by
      which diastolic dysfunction associated with prolonged DT impairs optimal filling.

PMID- 16891407
TI  - Cardiac myofibroblasts differentiated in 3D culture exhibit distinct changes in
      collagen I production, processing, and matrix deposition.
AB  - Myofibroblasts are a differentiated fibroblast cell type characterized by
      increased contractile capacity and elevated production of extracellular matrix
      (ECM) proteins. In the heart, myofibroblast expression is implicated in fibrosis
      associated with pressure-overload hypertrophy, among other pathologies. Although
      enhanced expression of ECM proteins by myofibroblasts is established, few studies
      have addressed the nature of the ECM deposited by myofibroblasts. To characterize
      ECM production and assembly by cardiac myofibroblasts, we developed a three
      dimensional (3D) culture system using primary cardiac fibroblasts seeded into a
      nylon mesh that allows us to reversibly interconvert between myofibroblast and
      fibroblast phenotypes. We report that an increase in collagen I production by
      myofibroblasts was accompanied by a significant increase in collagen deposition
      into insoluble ECM. Furthermore, myofibroblasts exhibited increased levels of
      procollagen alpha1(I) with C-propeptide attached (and N-propeptide removed)
      relative to procollagen alpha1(I) compared with fibroblast cultures. An increase
      in production of the myofibroblast-associated splice variant of fibronectin (EDA
      Fn) was seen in myofibroblast 3D cultures. Because the regulation of procollagen
      I processing is known to have profound effects on ECM assembly, differences in
      procollagen I secretion and maturation coupled with expression of EDA-Fn are
      shown to contribute to the production of a distinct ECM by the cardiac
      myofibroblast.

PMID- 16891404
TI  - Contributions of astrocytes and CO to pial arteriolar dilation to glutamate in
      newborn pigs.
AB  - Astrocytes can act as intermediaries between neurons and cerebral arterioles to
      regulate vascular tone in response to neuronal activity. Release of glutamate
      from presynaptic neurons increases blood flow to match metabolic demands. CO is a
      gasotransmitter that can be related to neural function and blood flow regulation
      in the brain. The present study addresses the hypothesis that glutamatergic
      stimulation promotes perivascular astrocyte CO production and pial arteriolar
      dilation in the newborn brain. Experiments used anesthetized newborn pigs with
      closed cranial windows, piglet astrocytes, and cerebrovascular endothelial cells
      in primary culture and immunocytochemical visualization of astrocytic markers.
      Pial arterioles and arteries of newborn pigs are ensheathed by astrocytes
      visualized by glial fibrillary acidic protein staining. Treatment (2 h) of
      astrocytes in culture with L-2-alpha-aminoadipic acid (L-AAA), followed by 14 h
      in toxin free medium, dose-dependently increased cell detachment, suggesting
      injury. Conversely, 16 h of continuous exposure to L-AAA caused no decrease in
      endothelial cell attachment. In vivo, topical L-AAA (2 mM, 5 h) disrupted the
      cortical glia limitans histologically. Such treatment also eliminated pial
      arteriolar dilation to the astrocyte-dependent dilator ADP and to glutamate but
      not to isoproterenol or CO. Glutamate stimulated CO production by the brain
      surface that also was abolished following L-AAA. In contrast, tetrodotoxin
      blocked dilation to N-methyl-D-aspartate but not to glutamate, isoproterenol, or
      CO or the glutamate-induced increase in CO. The concurrent loss of CO production
      and pial arteriolar dilation to glutamate following astrocyte injury suggests
      astrocytes may employ CO as a gasotransmitter for glutamatergic cerebrovascular
      dilation.

PMID- 16891408
TI  - Altered nitric oxide mechanism within the paraventricular nucleus contributes to
      the augmented carotid body chemoreflex in heart failure.
AB  - Our previous study demonstrated a contribution of the paraventricular nucleus
      (PVN) of the hypothalamus in the processing of the carotid body (CB) chemoreflex.
      Nitric oxide (NO) (within the PVN), known to modulate autonomic function, is
      altered in rats with heart failure (HF). Therefore, the goal of the present study
      was to examine the influence of endogenous and exogenous NO within the PVN on the
      sympathoexcitatory component of the peripheral chemoreflex in normal and HF
      states. We measured mean arterial blood pressure, heart rate, renal sympathetic
      nerve activity (RSNA), and phrenic nerve activity (PNA) in sham-operated and HF
      rats (6-8 wk after coronary artery ligation) after incremental doses of potassium
      cyanide (25-100 mug/kg iv). There was potentiation of the reflex responses in HF
      compared with sham-operated rats. Bilateral microinjection of an inhibitor of NO
      synthase, N(G)-monomethyl-l-arginine (50 pmol), into the PVN augmented the RSNA
      and PNA response to peripheral chemoreceptor stimulation in sham-operated rats
      but had no effect in HF rats. Conversely, bilateral microinjection of a NO donor,
      sodium nitroprusside (50 nmol), into the PVN attenuated the RSNA response of the
      peripheral chemoreflex in sham-operated rats but to a smaller extent in HF rats.
      These data indicate that 1) NO within the PVN plays an important role in the
      processing of the CB chemoreflex and 2) there is an impairment of the NO function
      within the PVN of HF rats, which contributes to an augmented peripheral
      chemoreflex and subsequent elevation of sympathetic activity in HF.

PMID- 16891409
TI  - Mitochondrial dysfunction and tau hyperphosphorylation in Ts1Cje, a mouse model
      for Down syndrome.
AB  - Trisomy 21 or Down syndrome (DS) is the most common genetic birth defect
      associated with mental retardation. The over-expression of genes on chromosome
      21, including SOD1 (Cu/Zn superoxide dismutase) and APP (amyloid-beta precursor
      protein) is believed to underlie the increased oxidative stress and
      neurodegeneration commonly described in DS. However, a segmental trisomy 16 mouse
      model for DS, Ts1Cje, has a subset of triplicated human chromosome 21 gene
      orthologs that exclude APP and SOD1. Here, we report that Ts1Cje brain shows
      decreases of mitochondrial membrane potential and ATP production, increases of
      reactive oxygen species, hyperphosphorylation of tau without NFT formation,
      increase of GSK3beta and JNK/SAPK activities and unaltered AbetaPP metabolism.
      Our findings suggest that genes on the trisomic Ts1Cje segment other than APP and
      SOD1 can cause oxidative stress, mitochondrial dysfunction and
      hyperphosphorylation of tau, all of which may play critical roles in the
      pathogenesis of mental retardation in DS.

PMID- 16891410
TI  - Infiltrating neutrophils mediate the initial angiogenic switch in a mouse model
      of multistage carcinogenesis.
AB  - Matrix metalloprotease type 9 (MMP-9) has been functionally implicated in VEGF
      activation, the induction and maintenance of chronic angiogenesis, and early
      stage tumor growth in a number of mouse models of cancer. In this article, we
      have identified two inflammatory cell types that are major sources of MMP-9 in
      the angiogenic stages of pancreatic islet carcinogenesis that unfold in RIP1-Tag2
      transgenic mice. MMP-9-expressing neutrophils were predominantly found inside
      angiogenic islet dysplasias and tumors, whereas MMP-9-expressing macrophages were
      localized along the periphery of such lesions. Transient depletion of neutrophils
      significantly suppressed VEGF:VEGF-receptor association, a signature of MMP-9
      activity, and markedly reduced the frequency of initial angiogenic switching in
      dysplasias. Thus infiltrating neutrophils can play a crucial role in activating
      angiogenesis in a previously quiescent tissue vasculature during the early stages
      of carcinogenesis.

PMID- 16891411
TI  - Vesicles surfing on a lipid bilayer: self-induced haptotactic motion.
AB  - Haptotaxis is a mechanism proposed at the end of the 1960s to explain cell
      motility. It describes cell movement induced by an adhesion gradient. In this
      work, we present evidence for self-induced haptotaxis using negatively charged
      giant vesicles interacting with positively charged supported lipid bilayers,
      which has not been previously described. Depending on the charge of the vesicle,
      we observed different behaviors. At low charge, no adhesion occurs. At high
      charge, the vesicle adheres but does not move. In a restricted range of
      intermediate charge densities, we found that the vesicle moves spontaneously with
      velocities of the order of a few micrometers per second over distances of >100
      microm. We show that a local lipid transfer between the giant vesicle and the
      supported lipid bilayer takes place during the adhesion, breaking the symmetry
      and inducing a lateral charge gradient. This charge gradient polarizes the giant
      vesicle and induces its motion. To explain our observations, we propose a scaling
      model that relates the adhesion energy to the velocity of vesicle motion and to
      the characteristic lipid transfer time. Our measurements indicate that the
      effective adhesion energy is strongly reduced by counterions, which are
      dynamically trapped between the vesicle and the supported bilayer.

PMID- 16891412
TI  - Rewiring the severe acute respiratory syndrome coronavirus (SARS-CoV)
      transcription circuit: engineering a recombination-resistant genome.
AB  - Live virus vaccines provide significant protection against many detrimental human
      and animal diseases, but reversion to virulence by mutation and recombination has
      reduced appeal. Using severe acute respiratory syndrome coronavirus as a model,
      we engineered a different transcription regulatory circuit and isolated
      recombinant viruses. The transcription network allowed for efficient expression
      of the viral transcripts and proteins, and the recombinant viruses replicated to
      WT levels. Recombinant genomes were then constructed that contained mixtures of
      the WT and mutant regulatory circuits, reflecting recombinant viruses that might
      occur in nature. Although viable viruses could readily be isolated from WT and
      recombinant genomes containing homogeneous transcription circuits, chimeras that
      contained mixed regulatory networks were invariantly lethal, because viable
      chimeric viruses were not isolated. Mechanistically, mixed regulatory circuits
      promoted inefficient subgenomic transcription from inappropriate start sites,
      resulting in truncated ORFs and effectively minimize viral structural protein
      expression. Engineering regulatory transcription circuits of intercommunicating
      alleles successfully introduces genetic traps into a viral genome that are lethal
      in RNA recombinant progeny viruses.

PMID- 16891413
TI  - Vaccination against weight gain.
AB  - Obesity endangers the lives of millions of people worldwide, through
      comorbidities such as heart disease, cancers, type 2 diabetes, stroke, arthritis,
      and major depression. New approaches to control body weight remain a high
      priority. Vaccines traditionally have been used to protect against infectious
      diseases and, more recently, for unconventional targets such as drug addiction.
      Methodologies that could specifically modulate the bioavailability of an
      endogenous molecule that regulates energy balance might provide a new foundation
      for treating obesity. Here we show that active vaccination of mature rats with
      ghrelin immunoconjugates decreases feed efficiency, relative adiposity, and body
      weight gain in relation to the immune response elicited against ghrelin in its
      active, acylated form. Three active vaccines based on the 28-aa residue sequence
      of ghrelin, a gastric endocrine hormone, were used to immunize adult male Wistar
      rats (n = 17). Synthetic ghrelin analogs were prepared that spanned residues 1-10
      [ghrelin (1-10) Ser-3(butanoyl) hapten, Ghr1], 13-28 [ghrelin (13-28) hapten,
      Ghr2], and 1-28 [ghrelin(1-28) Ser-3(butanoyl) hapten, Ghr3], and included n
      butanoyl esters at Ser-3. Groups immunized with Ghr1 or Ghr3 showed greater and
      more selective plasma binding capacity for the active, Ser-3-(n-octanoyl) form of
      ghrelin as compared with Ghr2 or keyhole limpet hemocyanin vaccinated controls.
      Accordingly, they gained less body weight, with sparing of lean mass and
      preferential reduction of body fat, consistent with reduced circulating leptin
      levels. The ratio of brain/serum ghrelin levels was lower in rats with strong
      anti-ghrelin immune responses. Effects were not attributable to nonspecific
      inflammatory responses. Vaccination against the endogenous hormone ghrelin can
      slow weight gain in rats by decreasing feed efficiency.

PMID- 16891414
TI  - The active FMR1 promoter is associated with a large domain of altered chromatin
      conformation with embedded local histone modifications.
AB  - We have analyzed the effects of gene activation on chromatin conformation
      throughout an approximately 170-kb region comprising the human fragile X locus,
      which includes a single expressed gene, FMR1 (fragile X mental retardation 1). We
      have applied three approaches: (i) chromosome conformation capture, which
      assesses relative interaction frequencies of chromatin segments; (ii) an
      extension of this approach that identifies domains whose conformation differs
      from the average, which we developed and named chromosome conformation profiling;
      and (iii) ChIP analysis of histone modifications. We find that, in normal cells
      where FMR1 is active, the FMR1 promoter is at the center of a large (
      approximately 50 kb) domain of reduced intersegment interactions. In contrast, in
      fragile X cells where FMR1 is inactive, chromatin conformation is uniform across
      the entire region. We also find that histone modifications that are
      characteristic of active genes occur tightly localized around the FMR1 promoter
      in normal cells and are absent in fragile X cells. Therefore, the expression
      correlated change in conformation affects a significantly larger domain than that
      marked by histone modifications. Domain-wide changes in interaction probability
      could reflect increased chromatin expansion and may also be related to an altered
      spatial disposition that results in increased intermingling with unrelated loci.
      The described approaches are widely applicable to the study of conformational
      changes of any locus of interest.

PMID- 16891415
TI  - Evaluation of RNA-binding specificity of aminoglycosides with DNA microarrays.
AB  - We have developed methods for using DNA array technology to probe the entire
      transcriptome to determine the RNA-binding specificity of ligands. Two methods
      were investigated. In the first method, the RNA-binding aminoglycoside antibiotic
      tobramycin was covalently linked to magnetic beads. The beads were bound to human
      liver mRNA and washed, and specifically bound RNA was eluted, amplified, and
      analyzed with DNA array technology. A small number of genes were found to bind
      specifically to the tobramycin beads. In the second method, the aminoglycoside
      ligand was added directly to the array hybridization reaction, and the signal was
      compared with a control experiment in the absence of ligand. The aminoglycosides
      were found to interfere with a small percentage of all hybridization events.
      These methods differ from traditional DNA array experiments in that the readout
      is a direct measure of the interaction between mRNA and a ligand, rather than an
      indirect measure of effect on expression. We expect that the results will lead to
      the discovery of new aminoglycoside-binding RNA motifs and may also have
      relevance toward understanding and overcoming the side effects observed with
      these antibiotics in the clinic.

PMID- 16891416
TI  - Involvement of Toll-like receptor 5 in the recognition of flagellated bacteria.
AB  - Toll-like receptors (TLRs) are key components of the immune system that detect
      microbial infection and trigger antimicrobial host defense responses. TLR5 is a
      sensor for monomeric flagellin, which is a component of bacterial flagella known
      to be a virulence factor. In this study we generated TLR5-deficient mice and
      investigated the role of TLR5 signaling in the detection of flagellin and
      antibacterial immune responses to Salmonella typhimurium and Pseudomonas
      aeruginosa. We found that TLR5 is essential for the recognition of bacterial
      flagellin both in vivo and ex vivo. TLR5 contribution to antibacterial host
      response to i.p. infection with S. typhimurium or intranasal administration of P.
      aeruginosa may be masked by TLR4 or other sensing mechanisms. By using radiation
      bone marrow chimera, we showed that upon i.p. injection of flagellin immune
      responses are mediated by lymphoid cells, whereas resident cells are required for
      the initiation of response upon intranasal flagellin administration. These
      results suggest that flagellin recognition in different organs is mediated by
      distinct TLR5-expressing cells and provide insights into the cooperation of the
      TLR5 and TLR4 signaling pathways used by the innate immune system in the
      recognition of bacterial pathogens.

PMID- 16891417
TI  - Basonuclins 1 and 2, whose genes share a common origin, are proteins with widely
      different properties and functions.
AB  - Basonuclin (bn) 1 possesses three separated pairs of zinc fingers and a nuclear
      localization signal. It is largely confined to the basal cells of stratified
      squamous epithelia and to reproductive germ cells. bn1 can shuttle between the
      nucleus and the cytoplasm, and its location is correlated with the proliferative
      potential of the cell. The recently discovered bn2 also possesses three separated
      pairs of zinc fingers and a nuclear localization signal. Conservation of the zinc
      fingers and the nuclear localization signal by bn1 and bn2 indicates a common
      origin. However, in contrast to bn1, bn2 is found in virtually every cell type
      and is confined to the nucleus. Bn2 but not bn1 colocalizes with SC35 in nuclear
      speckles and, therefore, is likely to have a function in nuclear processing of
      mRNA.

PMID- 16891418
TI  - Cortical feedback depolarization waves: a mechanism of top-down influence on
      early visual areas.
AB  - Despite the lack of direct evidence, it is generally believed that top-down
      signals are mediated by the abundant feedback connections from higher- to lower
      order sensory areas. Here we provide direct evidence for a top-down mechanism. We
      stained the visual cortex of the ferret with a voltage-sensitive dye and
      presented a short-duration contrast square. This elicited an initial feedforward
      and lateral spreading depolarization at the square representation in areas 17 and
      18. After a delay, a broad feedback wave (FBW) of neuron peak depolarization
      traveled from areas 21 and 19 toward areas 18 and 17. In areas 18 and 17, the FBW
      contributed the peak depolarization of dendrites of the neurons representing the
      square, after which the neurons decreased their depolarization and firing.
      Thereafter, the peak depolarization surrounded the figure representation over
      most of areas 17 and 18 representing the background. Thus, the FBW is an example
      of a well behaved long-range communication from higher-order visual areas to
      areas 18 and 17, collectively addressing very large populations of neurons
      representing the visual scene. Through local interaction with feedforward and
      lateral spreading depolarization, the FBW differentially activates neurons
      representing the object and neurons representing the background.

PMID- 16891420
TI  - Structure-activity relationships by interligand NOE-based design and synthesis of
      antiapoptotic compounds targeting Bid.
AB  - Bcl-2 family proteins play a crucial role in tissue homeostasis and apoptosis
      (programmed cell death). Bid is a proapoptotic member of the Bcl-2 family,
      promoting cell death when activated by caspase-8. Following an NMR-based approach
      (structure-activity relationships by interligand NOE) we were able to identify
      two chemical fragments that bind on the surface of Bid. Covalent linkage of the
      two fragments led to high-affinity bidentate derivatives. In vitro and in-cell
      assays demonstrate that the compounds prevent tBid translocation to the
      mitochondrial membrane and the subsequent release of proapoptotic stimuli and
      inhibit neuronal apoptosis in the low micromolar range. Therefore, by using a
      rational chemical-biology approach, we derived antiapoptotic compounds that may
      have a therapeutic potential for disorders associated with Bid activation, e.g.,
      neurodegenerative diseases, cerebral ischemia, or brain trauma.

PMID- 16891419
TI  - Early evolution of animal cell signaling and adhesion genes.
AB  - In stark contrast to the rapid morphological radiation of eumetazoans during the
      Cambrian explosion, the simple body plan of sponges (Phylum Porifera) emerged
      from the Cambrian relatively unchanged. Although the genetic and developmental
      underpinnings of these disparate evolutionary outcomes are unknown, comparisons
      between modern sponges and eumetazoans promise to reveal the extent to which
      critical genetic factors were present in their common ancestors. Two particularly
      interesting classes of genes in this respect are those involved in cell signaling
      and adhesion. These genes help guide development and morphogenesis in modern
      eumetazoans, but the timing and sequence of their origins is unknown. Here, we
      demonstrate that the sponge Oscarella carmela, one of the earliest branching
      animals, expresses core components of the Wnt, transforming growth factor beta,
      receptor tyrosine kinase, Notch, Hedgehog, and Jak/Stat signaling pathways.
      Furthermore, we identify sponge homologs of nearly every major eumetazoan cell
      adhesion gene family, including those that encode cell-surface receptors,
      cytoplasmic linkers, and extracellular-matrix proteins. From these data, we infer
      that key signaling and adhesion genes were in place early in animal evolution,
      before the divergence of sponge and eumetazoan lineages.

PMID- 16891423
TI  - Descriptive spatial analysis of scrapie-affected flocks in Great Britain between
      January 1993 and December 2002.
AB  - The spatial distribution of sheep flocks in Great Britain with confirmed clinical
      scrapie between January 1993 and December 2002 inclusive was investigated by
      using kernel density estimation and a cluster scan test statistic. Six
      statistically significant clusters were identified: three were lower risk, and
      were centred on the north-western coast of Scotland, the north-western coast of
      Wales and the South Yorkshire/Pennine region; three were of higher risk, and were
      centred in the central south, North Yorkshire and north Cumbria. General
      knowledge and the results of previous epidemiological studies were used to
      generate biologically plausible hypotheses that might explain these findings.
      They included aspects of flock management and disease transmission, and factors
      associated with the identification of cases, including their detection,
      recognition and, in particular, reporting levels, as well as diagnosis and animal
      movements.

PMID- 16891421
TI  - Convergent evidence that oligodendrocyte lineage transcription factor 2 (OLIG2)
      and interacting genes influence susceptibility to schizophrenia.
AB  - Abnormal oligodendrocyte function has been postulated as a primary etiological
      event in schizophrenia. Oligodendrocyte lineage transcription factor 2 (OLIG2)
      encodes a transcription factor central to oligodendrocyte development. Analysis
      of OLIG2 in a case-control sample (n = approximately 1,400) in the U.K. revealed
      several SNPs to be associated with schizophrenia (minimum P = 0.0001, gene-wide P
      = 0.0009). To obtain independent support for this association, we sought evidence
      for genetic interaction between OLIG2 and three genes of relevance to
      oligodendrocyte function for which we have reported evidence for association with
      schizophrenia: CNP, NRG1, and ERBB4. We found interaction effects on disease risk
      between OLIG2 and CNP (minimum P = 0.0001, corrected P = 0.008) for interaction
      with ERBB4 (minimum P = 0.002, corrected P = 0.04) but no evidence for
      interaction with NRG1. To investigate the biological plausibility of the
      interactions, we sought correlations between the expression of the genes. The
      results were similar to those of the genetic interaction analysis. OLIG2
      expression significantly correlated in cerebral cortex with CNP (P < 10(-7)) and
      ERBB4 (P = 0.002, corrected P = 0.038) but not NRG1. In mouse striatum, Olig2 and
      Cnp expression also was correlated, and linkage analysis for trans-effects on
      gene expression suggests that each locus regulates the other's expression. Our
      data provide strong convergent evidence that variation in OLIG2 confers
      susceptibility to schizophrenia alone and as part of a network of genes
      implicated in oligodendrocyte function.

PMID- 16891422
TI  - Transient receptor potential family members PKD1L3 and PKD2L1 form a candidate
      sour taste receptor.
AB  - Animals use their gustatory systems to evaluate the nutritious value, toxicity,
      sodium content, and acidity of food. Although characterization of molecular
      identities that receive taste chemicals is essential, molecular receptors
      underlying sour taste sensation remain unclear. Here, we show that two transient
      receptor potential (TRP) channel members, PKD1L3 and PKD2L1, are coexpressed in a
      subset of taste receptor cells in specific taste areas. Cells expressing these
      molecules are distinct from taste cells having receptors for bitter, sweet, or
      umami tastants. The PKD2L1 proteins are accumulated at the taste pore region,
      where taste chemicals are detected. PKD1L3 and PKD2L1 proteins can interact with
      each other, and coexpression of the PKD1L3 and PKD2L1 is necessary for their
      functional cell surface expression. Finally, PKD1L3 and PKD2L1 are activated by
      various acids when coexpressed in heterologous cells but not by other classes of
      tastants. These results suggest that PKD1L3 and PKD2L1 heteromers may function as
      sour taste receptors.

PMID- 16891424
TI  - M gene analysis of atypical strains of feline and canine coronavirus circulating
      in an Austrian animal shelter.
AB  - Coronavirus-positive samples of faeces collected in an Austrian animal shelter
      from 12 cats and 10 dogs were analysed by reverse transcriptase-pcr with primers
      amplifying a segment of the M protein gene, and by sequence analysis. In
      addition, the samples were subjected to S gene typing, using primers that
      differentiated between feline coronavirus (fcov) types I and II. A phylogenetic
      analysis of the M gene sequences revealed not only clearly segregating canine
      coronavirus (ccov) in the dogs, typical ccov sequences and the recently described
      fcov-like ccov, but also at least two genetic clusters of fcov in the cats, one
      species-specific, the other more closely related to fcov-like ccov. The M gene
      sequences of these new feline strains had at most 88 per cent identity with the
      fcov-like ccov strain 259/01 and only up to 85 per cent with any fcov sequence
      available in GenBank. In the phylogenetic tree they occupy an intermediate
      position between feline and canine coronaviruses.

PMID- 16891425
TI  - Wild rabbits (Oryctolagus cuniculus) as potential carriers of verocytotoxin
      producing Escherichia coli.
AB  - In summer 2001, visitors to a wildlife park in Norfolk, uk, became infected with
      verocytotoxin-producing Escherichia coli (vtec) O157, which was associated with
      wild rabbit faeces. The rabbits lived in an adjacent field together with E coli
      O157-positive cattle. A pilot study was therefore performed to investigate the
      factors affecting the association between E coli O157-positive cattle and wild
      rabbits. Samples of faeces were taken from 16 herds of cattle that lived close to
      populations of wild rabbits. Analysis by culture and pcr showed that seven of the
      herds were positive for E coli O157. Faeces were collected from individual
      rabbits at six of these farms during late winter, when there were few rabbits,
      and during high summer, when there were many. None of the 32 samples collected on
      two farms in late winter was positive for E coli O157, but eight of 97 samples
      collected in summer were positive on four of the six farms. pcr analysis for
      vtec, including non-O157, showed that 20 of the 97 samples were positive.

PMID- 16891426
TI  - Fatal babesiosis in an untravelled British dog.

PMID- 16891428
TI  - Detection of strychnine by gas chromatography-mass spectrometry in the carcase of
      a Bonelli's eagle (Hieraaetus fasciatus).

PMID- 16891427
TI  - Prevalence of brucellosis and its association with reproductive problems in cows
      in Bangladesh.

PMID- 16891429
TI  - Risk of botulism in cattle and sheep arising from contact with broiler litter.

PMID- 16891431
TI  - Euthanasia of greyhounds.

PMID- 16891432
TI  - Equine infectious anaemia in Ireland.

PMID- 16891430
TI  - FMD control strategies.

PMID- 16891433
TI  - Spontaneous T wave inversion after ventricular pacing: what is the probable
      mechanism?

PMID- 16891434
TI  - Chronic vulvovaginal pruritus treated successfully with GnRH analogue.
AB  - A Medline search shows that this is the first reported case where vulvovaginal
      pruritus was treated successfully with a GnRH analogue. The report describes a
      patient with chronic premenstrual vulvovaginal pruritus thought to be
      attributable to autoimmune progesterone dermatitis.

PMID- 16891435
TI  - Assisted dying: the ongoing debate.

PMID- 16891436
TI  - Diagnostic approach to patients with suspected vasculitis.
AB  - Vasculitis presents several diagnostic challenges. Firstly, patients could
      present with protean clinical manifestations with a wide spectrum ranging from
      isolated cutaneous vasculitis to multisystem involvement. Secondly, there are
      several medical conditions that could mimic the presentation of vasculitis. The
      range of differential diagnosis is therefore broad. Thirdly, vasculitis could
      occur as a primary disorder or be secondary to various medical conditions. It
      becomes important to differentiate them, as treatment of some forms of vasculitis
      such as those that are secondary to infection or drugs, is different from that of
      primary vasculitis. Fourthly, there are several different forms of vasculitis.
      Some are benign and self limiting, while others have the potential to threaten
      vital organ function and life. It follows that a rational approach is required
      during evaluation of patients with suspected vasculitis.

PMID- 16891437
TI  - Management of urethral strictures.
AB  - Controlled clinical trials are unusual in surgery, rare in urology, and almost
      non-existent as far as the management of urethral stricture is concerned. What
      data there are come largely from so called "expert opinion" and the quality of
      this is variable. None the less, the number of so called experts, past and
      present, is comparatively small and in broad principle their views more or less
      coincide. Although this review is therefore inevitably biased, it is unlikely
      that expert opinion will take issue with most of the general points raised here.

PMID- 16891438
TI  - Interstitial lung disease: progress and problems.
AB  - Interstitial lung disease involves all areas of medicine as it often occurs in
      patients with comorbidities or as a consequence of systemic diseases and their
      treatment. Typically the physician is faced with a breathless patient, a
      diffusely abnormal chest radiograph, and a wide differential diagnosis. Progress
      has been made in using high resolution computed tomography as the key
      investigation in characterising the pattern and extent of the disease.
      Bronchoalveolar lavage is particularly important in excluding infection as a
      cause of diffuse lung infiltrates. Surgical lung biopsies have led to a new
      classification system for the range of histopathological patterns of disease that
      were previously known by the collective term cryptogenic fibrosing alveolitis.
      Problems persist in deciding when a surgical lung biopsy is clinically justified,
      in understanding the pathogenesis of these diseases, and in finding more
      effective treatments.

PMID- 16891439
TI  - Acne: more than skin deep.
AB  - Acne is one of the most prevalent skin conditions affecting teenagers. It is a
      disease of the pilosebaceous unit. Blockage of sebaceous glands and colonisation
      with Proionobacterium acnes leads to acne. Grading the severity of acne helps to
      determine the appropriate treatment. Treatment of acne should be started as early
      as possible to minimise the risk of scarring and adverse psychological effects.
      It should be tailored to the individual patient, the type of acne, its severity,
      the patient's ability to use the treatment, and the psychological state. Topical
      agents are the mainstay for treatment of mild acne. Moderate acne is treated with
      oral antibiotics. Resistance to antibiotics may be reduced by subsequent use of
      non-antibiotic topical medications. Severe acne is treated with isotretinoin, and
      this can lead to permanent remission. With better education and care given by
      medical profession, acne treatment could be significantly improved.

PMID- 16891441
TI  - Iatrogenic arsenic induced Mees' lines.

PMID- 16891440
TI  - Chronic hepatitis B in hepatocarcinogenesis.
AB  - Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world, and
      has a wide geographical variation. Eighty per cent of HCC is attributed to
      hepatitis B virus (HBV). The predominant carcinogenic mechanism of HBV associated
      HCC is through the process of liver cirrhosis, but direct oncogenic effects of
      HBV may also contribute. Prevention of HBV infections as well as effective
      treatment of chronic hepatitis B is still needed for the global control of HBV
      associated HCC. Continued investigation of the mechanisms of hepatocarcinogenesis
      will refine our current understanding of the molecular and cellular basis for
      neoplastic transformation in the liver.

PMID- 16891442
TI  - Fournier's gangrene and its emergency management.
AB  - Fournier's gangrene (FG) is a rare but life threatening disease. Although
      originally thought to be an idiopathic process, FG has been shown to have a
      predilection for patients with diabetes as well as long term alcohol misuse;
      however, it can also affect patients with non-obvious immune compromise. The
      nidus is usually located in the genitourinary tract, lower gastrointestinal
      tract, or skin. FG is a mixed infection caused by both aerobic and anaerobic
      bacterial flora. The development and progression of the gangrene is often
      fulminating and can rapidly cause multiple organ failure and death. Because of
      potential complications, it is important to diagnose the disease process as early
      as possible Although antibiotics and aggressive debridement have been broadly
      accepted as the standard treatment, the death rate remains high.

PMID- 16891443
TI  - Paracetamol availability and recent changes in paracetamol poisoning: is the 1998
      legislation limiting availability of paracetamol being followed?
AB  - OBJECTIVE: To determine the degree of adherence to legislation introduced in 1998
      restricting the availability of over the counter paracetamol. DESIGN: A
      prospective observational study. SETTING: An emergency department in an inner
      city London teaching hospital. Pharmacy and non-pharmacy outlets in south London.
      MAIN OUTCOME MEASURES: (1) The source of paracetamol ingested by 107 patients
      presenting with an acute paracetamol overdose (2001-2003) and (2) the ability to
      purchase paracetamol from pharmacy and non-pharmacy outlets in a manner
      contravening paracetamol pack size legislation (2004). RESULTS: Potentially toxic
      amounts of paracetamol in excess of pack size restrictions were purchased in 70%
      (17 of 24) of outlets. Forty six per cent of patients who had ingested a
      potentially toxic dose of paracetamol obtained the tablets in a manner
      contravening the 1998 legislation. CONCLUSION: Legislation limiting the
      availability of over the counter paracetamol is not being adhered to in south
      London. A significant number of patients ingesting a potentially toxic dose of
      paracetamol report purchasing the tablets in a manner contravening the
      legislation. Studies that attempt to assess the impact of the legislation need to
      be interpreted in the context of these results. Measures to enforce current
      legislation may help to reduce the severity of paracetamol poisoning in the UK.

PMID- 16891444
TI  - Effect of methionine loading on pulse wave analysis in elderly volunteers.
AB  - OBJECTIVE: To test the hypothesis that an acute increase in plasma homocysteine
      produced by methionine is associated with an acute increase in pulse wave
      velocity. DESIGN: A double blind, cross over, placebo controlled design was used
      and pulse wave velocity, plasma homocysteine, total cholesterol: high density
      lipoprotein ratio, plasma triglyceride, oxidised low density lipoprotein
      cholesterol concentrations, apolipoproteins A1 and B, and C reactive protein were
      measured between 12.5 and 20 hours after methionine loading or placebo. RESULTS:
      Between 12.5 and 20 hours after exposure to a methionine loading test, arterial
      pulse wave velocity showed no significant difference compared with placebo. At 12
      hours after exposure to the methionine loading test, in the presence of a
      controlled diet, triglyceride concentration significantly increased by 32.6%
      (p<0.02), cholesterol: high density lipoprotein ratio increased significantly by
      22.5% (p<0.05) compared with placebo. Simultaneously, systolic blood pressure
      increased significantly by 4.9% (p<0.02). CONCLUSION: In elderly volunteers,
      acute hyperhomocysteinaemia induced by methionine loading resulted in no overall
      significant delayed reduction in peripheral arterial distensibility. A
      significant deterioration in the lipid profile and increased blood pressure was
      seen during acute hyperhomocysteinaemia.

PMID- 16891445
TI  - Preventing fragility hip fracture in high risk groups: an opportunity missed.
AB  - OBJECTIVE: The national guideline recommends selective case finding as the main
      strategy by identification of high risk people. This study assessed whether high
      risk patients were identified before their presentation with fragility fracture.
      METHODS: A prospective study for 3.5 consecutive months on patients with low
      energy hip fractures to Brighton and Sussex University Hospital NHS Trusts, which
      serves a population of 460,000. Data were collected by interview using
      standardised form, medical record review, and communication with family
      physicians. Definition of high risk: (1) untreated hypogonadism (2)
      corticosteroid users (3) disorders with increased bone loss (4) previous
      fragility fractures. RESULTS: 98 patients were admitted with hip fracture. Thirty
      nine (40%) had at least one high risk factor. High risk patients (7 of 39, 18%)
      were no more likely to receive prophylaxis compared with patients without high
      risk factor (5 of 59, 8%) (p = 0.21). Previous fragility fracture (23) was the
      commonest risk factor followed by disorders with increased bone loss (10),
      premature menopause (10), and corticosteroid users (5). Fifteen patients (15%)
      had susceptibility to frequent falls and two had maternal history of
      osteoporosis. The proportion of treated patients were 20% (2 of 10) in premature
      menopause, 10% (1 of 10) in diseases with secondary osteoporosis, 13% (3 of 23)
      in previous fragility fracture, and 80% (4 of 5) in corticosteroid users (p =
      0.01) CONCLUSION: Prevention of hip fracture is still inadequate in high risk
      patients. Discrepancy seemed to exist in treatment frequency among different high
      risk groups suggesting that emphasis on prevention of osteoporosis has not been
      reinforced in all people at risk.

PMID- 16891447
TI  - Surgical trainees benefit from good consultant working practices: an audit on the
      effect on training of a new consultant rota.
AB  - PURPOSE: To retrospectively assess operative supervision for orthopaedic trainees
      over an 18 week period when trauma and orthopaedic consultants changed their on
      call working practice from one week on call to a four day/three day block, during
      a fortnight period. OUTCOME: The rota changes had important implications on
      workload and consultant availability to supervise juniors during operation with a
      positive effect upon training such that trauma surgery supervision rates
      increased significantly (p<0.001) after the introduction of these new working
      arrangements. Working life for consultants and ultimately patient care were also
      felt to improve and consultants' working hours were closer to the European
      working hours directives.

PMID- 16891448
TI  - Liposomal delivery as a mechanism to enhance synergism between anticancer drugs.

PMID- 16891446
TI  - Which sociodemographic factors are important on smoking behaviour of high school
      students? The contribution of classification and regression tree methodology in a
      broad epidemiological survey.
AB  - BACKGROUND: The purpose of this study is to evaluate the most important
      sociodemographic factors on smoking status of high school students using a broad
      randomised epidemiological survey. METHODS: Using in-class, self administered
      questionnaire about their sociodemographic variables and smoking behaviour, a
      representative sample of total 3304 students of preparatory, 9th, 10th, and 11th
      grades, from 22 randomly selected schools of Mersin, were evaluated and
      discriminative factors have been determined using appropriate statistics. In
      addition to binary logistic regression analysis, the study evaluated combined
      effects of these factors using classification and regression tree methodology, as
      a new statistical method. RESULTS: The data showed that 38% of the students
      reported lifetime smoking and 16.9% of them reported current smoking with a male
      predominancy and increasing prevalence by age. Second hand smoking was reported
      at a 74.3% frequency with father predominance (56.6%). The significantly
      important factors that affect current smoking in these age groups were increased
      by household size, late birth rank, certain school types, low academic
      performance, increased second hand smoking, and stress (especially reported as
      separation from a close friend or because of violence at home). Classification
      and regression tree methodology showed the importance of some neglected
      sociodemographic factors with a good classification capacity. CONCLUSIONS: It was
      concluded that, as closely related with sociocultural factors, smoking was a
      common problem in this young population, generating important academic and social
      burden in youth life and with increasing data about this behaviour and using new
      statistical methods, effective coping strategies could be composed.

PMID- 16891449
TI  - Pigment epithelium-derived factor: a multimodal tumor inhibitor.
AB  - Pigment epithelium-derived factor (PEDF), a noninhibitory member of the serine
      protease inhibitor (serpin) family, is a well-known potent endogenous inhibitor
      of angiogenesis. It has been known for years to be aberrantly expressed in ocular
      disorders, but in recent years, down-regulation has been shown to be prevalent in
      a range of cancers as well. This review describes the trimodal anticancer
      activities of this interesting protein: antiangiogenesis, apoptosis-mediated
      tumor suppression, and tumor cell differentiation. The key to successful
      antitumor therapy with this protein is the ability to synthesize the recombinant
      form of the protein (or its active shortened forms) and deliver at therapeutic
      doses or alternatively to use gene transfer technology to prolong the effect in
      vivo. Although there is a substantial amount of work carried out at the
      preclinical stage with this protein, more groundwork has to be done before PEDF
      is tested against cancer in clinical trials.

PMID- 16891451
TI  - Silymarin inhibits UV radiation-induced immunosuppression through augmentation of
      interleukin-12 in mice.
AB  - We have shown previously that silymarin, a plant flavonoid, inhibits UVB-induced
      photocarcinogenesis in mice. As UVB-induced immunosuppression has been implicated
      in the development of skin cancer, we investigated whether silymarin can modulate
      the effects of UVB radiation on the immune system. Treatment of C3H/HeN mice with
      topically applied silymarin (0.5 or 1.0 mg/cm(2)) or silibinin, a major component
      of silymarin, markedly inhibited UVB (180 mJ/cm(2))-induced suppression of
      contact hypersensitivity response in a local model of immunosuppression and had a
      moderate inhibitory effect in a systemic model of contact hypersensitivity.
      Silymarin reduced the UVB-induced enhancement of the levels of the
      immunosuppressive cytokine, interleukin (IL)-10, in the skin and draining lymph
      nodes and enhanced the levels of the immunostimulatory cytokine, IL-12.
      Intraperitoneal injection of mice treated with silymarin with an endotoxin-free
      neutralizing anti-IL-12 antibody abrogated the protective effects of the
      silymarin against UVB-induced suppression of the contact hypersensitivity
      response. Furthermore, the treatment of silymarin did not prevent UVB-induced
      suppression of the contact hypersensitivity response in IL-12 knockout mice but
      prevented it in their wild-type mice. Moreover, i.p. injection of IL-12 to
      silymarin-treated or non-silymarin-treated IL-12 knockout mice resulted in an
      enhanced response to contact hypersensitivity compared with the response in mice
      that were exposed to either UVB alone or silymarin plus UVB. These data indicate
      for the first time that silymarin has the ability to protect mice from UVB
      induced immunosuppression and that this protective effect is mediated, at least
      in part, through IL-12.

PMID- 16891450
TI  - Discovery and characterization of inhibitors of human palmitoyl acyltransferases.
AB  - The covalent attachment of palmitate to specific proteins by the action of
      palmitoyl acyltransferases (PAT) plays critical roles in the biological
      activities of several oncoproteins. Two PAT activities are expressed by human
      cells: type 1 PATs that modify the farnesyl-dependent palmitoylation motif found
      in H- and N-Ras, and type 2 PATs that modify the myristoyl-dependent
      palmitoylation motif found in the Src family of tyrosine kinases. We have
      previously shown that the type 1 PAT HIP14 causes cellular transformation. In the
      current study, we show that mRNA encoding HIP14 is up-regulated in a number of
      types of human tumors. To assess the potential of HIP14 and other PATs as targets
      for new anticancer drugs, we developed three cell-based assays suitable for high
      throughput screening to identify inhibitors of these enzymes. Using these
      screens, five chemotypes, with activity toward either type 1 or type 2 PAT
      activity, were identified. The activity of the hits were confirmed using assays
      that quantify the in vitro inhibition of PAT activity, as well as a cell-based
      assay that determines the abilities of the compounds to prevent the localization
      of palmitoylated green fluorescent proteins to the plasma membrane.
      Representative compounds from each chemotype showed broad antiproliferative
      activity toward a panel of human tumor cell lines and inhibited the growth of
      tumors in vivo. Together, these data show that PATs, and HIP14 in particular, are
      interesting new targets for anticancer compounds, and that small molecules with
      such activity can be identified by high-throughput screening.

PMID- 16891452
TI  - Telomerase inhibition enhances the response to anticancer drug treatment in human
      breast cancer cells.
AB  - Breast cancer is the most common malignancy among women. Current therapies for
      breast tumors are based on the use of chemotherapeutic drugs that are quite toxic
      for the patients and often result in resistance. Telomerase is up-regulated in
      95% of breast carcinomas but not in adjacent normal tissues. Therefore, it
      represents a very promising target for anticancer therapies. Unfortunately, the
      antiproliferative effects of telomerase inhibition require extensive telomere
      shortening before they are fully present. Combining telomerase inhibition with
      common chemotherapeutic drugs can be used to reduce this lag phase and induce
      tumor cell death more effectively. Few studies have analyzed the effects of
      telomerase inhibition in combination with anticancer drugs in breast cancer
      cells. In this study, we inhibited telomerase activity in two breast cancer cell
      lines using a dominant-negative human telomerase reverse transcriptase and
      analyzed cell viability after treatment with different anticancer compounds. We
      found that dominant-negative human telomerase reverse transcriptase efficiently
      inhibits telomerase activity and causes telomere shortening over time. Moreover,
      cells in which telomerase was suppressed were more sensitive to anticancer agents
      independently of their mechanism of action and this sensitization was dependent
      on the presence of shorter telomeres. Altogether, our data show that blocking
      telomere length maintenance in combination with anticancer drugs can be used as
      an effective way to induce death of breast cancer cells.

PMID- 16891453
TI  - Regulatory role of c-Met in insulin-like growth factor-I receptor-mediated
      migration and invasion of human pancreatic carcinoma cells.
AB  - Pancreatic carcinoma cells overexpress the insulin-like growth factor-I (IGF-I)
      receptor (IGF-IR) and the hepatocyte growth factor (HGF) receptor, c-Met, which
      are both known to mediate tumor cell migration and invasion. We hypothesized that
      IGF-IR and c-Met cooperate to induce migration and invasion of human pancreatic
      carcinoma cells and that IGF-I-mediated migration and invasion depend on c-Met.
      Migration and invasion assays were done with the human pancreatic cancer cell
      line L3.6pl treated with PBS, IGF-I, HGF, or IGF-I plus HGF. To determine if c
      Met is necessary for IGF-IR-mediated migration and invasion, c-Met was down
      regulated in L3.6pl cells via adenoviral infection with a c-Met ribozyme before
      IGF-I treatment. IGF-I and HGF increased cell migration and invasion.
      Furthermore, IGF-I plus HGF had a greater than additive effect on cell migration
      and invasion compared with either growth factor alone. Down-regulation of c-Met
      nearly completely inhibited IGF-I-mediated migration and invasion. Our findings
      suggest that IGF-IR and c-Met cooperate to induce migration and invasion of human
      pancreatic carcinoma cells. Furthermore, c-Met is required for both HGF- and IGF
      I-mediated migration and invasion. Elucidation of the signaling pathways that
      contribute to tumor progression and metastasis should provide a foundation for
      the development of targeted therapies for pancreatic carcinoma.

PMID- 16891454
TI  - Antisense locked nucleic acids efficiently suppress BCR/ABL and induce cell
      growth decline and apoptosis in leukemic cells.
AB  - Chronic myeloid leukemia (CML) develops when a hematopoietic stem cell acquires
      the Philadelphia chromosome carrying the BCR/ABL fusion gene. This gives the
      transformed cells a proliferative advantage over normal hematopoietic cells.
      Silencing the BCR/ABL oncogene by treatment with specific drugs remains an
      important therapeutic goal. In this work, we used locked nucleic acid (LNA)
      modified oligonucleotides to silence BCR/ABL and reduce CML cell proliferation,
      as these oligonucleotides are resistant to nucleases and exhibit an exceptional
      affinity for cognate RNA. The anti-BCR/ABL oligonucleotides were designed as LNA
      DNA gapmers, consisting of end blocks of 3/4 LNA monomers and a central DNA
      stretch of 13/14 deoxyribonucleotides. The gapmers were complementary to the b2a2
      and b3a2 mRNA junctions with which they form hybrid duplexes that have melting
      temperatures of 79 degrees C and 75 degrees C, respectively, in a 20 mmol/L NaCl
      buffered (pH 7.4) solution. Like DNA, the designed LNA-DNA gapmers were capable
      of activating RNase H and promote cleavage of the target b2a2 and b3a2 BCR/ABL
      mRNAs. The treatment of CML cells with junction-specific antisense gapmers
      resulted in a strong and specific reduction of the levels of BCR/ABL transcripts
      ( approximately 20% of control) and protein p210(BCR/ABL) ( approximately 30% of
      control). Moreover, the antisense oligonucleotides suppressed cell growth up to
      40% of control and induced apoptosis, as indicated by the increase of caspase-3/7
      activity in the treated cells. Finally, the b2a2-specific antisense gapmer used
      in combination with STI571 (imatinib mesylate), a tyrosine kinase inhibitor of
      p210(BCR/ABL), produced an enhanced antiproliferative effect in KYO-1 cells,
      which compared with K562 cells are refractory to STI571. The data of this study
      support the application of BCR/ABL antisense LNA-DNA gapmers, used either alone
      or in combination with STI571, as potential antileukemic agents.

PMID- 16891455
TI  - CRA-026440: a potent, broad-spectrum, hydroxamic histone deacetylase inhibitor
      with antiproliferative and antiangiogenic activity in vitro and in vivo.
AB  - CRA-026440 is a novel, broad-spectrum, hydroxamic acid-based inhibitor of histone
      deacetylase (HDAC) that shows antitumor and antiangiogenic activities in vitro
      and in vivo preclinically. CRA-026440 inhibited pure recombinant isozymes HDAC1,
      HDAC2, HDAC3/SMRT, HDAC6, HDAC8, and HDAC10 in the nanomolar range. Treatment of
      cultured tumor cell lines grown in vitro with CRA-026440 resulted in the
      accumulation of acetylated histone and acetylated tubulin, leading to an
      inhibition of tumor cell growth and the induction of apoptosis. CRA-026440
      inhibited ex vivo angiogenesis in a dose-dependent manner. CRA-026440
      parenterally given to mice harboring HCT116 or U937 human tumor xenografts
      resulted in a statistically significant reduction in tumor growth. CRA-026440,
      when used in combination with Avastin, achieved greater preclinical efficacy in
      HCT 116 colorectal tumor model. Inhibition of tumor growth was accompanied by an
      increase in the acetylation of alpha-tubulin in peripheral blood mononuclear
      cells and an alteration in the expression of many genes in the tumors, including
      several involved in angiogenesis, apoptosis, and cell growth. These results
      reveal CRA-026440 to be a novel HDAC inhibitor with potent antitumor activity.

PMID- 16891456
TI  - 5-Methoxy-1,2-dimethyl-3-[(4-nitrophenoxy)methyl]indole-4,7-dione, a mechanism
      based inhibitor of NAD(P)H:quinone oxidoreductase 1, exhibits activity against
      human pancreatic cancer in vitro and in vivo.
AB  - The enzyme NAD(P)H:quinone oxidoreductase 1 (NQO1) has been found to be up
      regulated in pancreatic cancer as well as many other solid tumors. A recent study
      showed that inhibition of NQO1 in pancreatic cancer cells using the nonselective
      inhibitor dicumarol suppressed the malignant phenotype. The authors suggested
      that inhibition of cell growth might result from an increase in intracellular
      superoxide production due to inhibition of NQO1. We have recently shown that NQO1
      can directly scavenge superoxide and this effect may become physiologically
      relevant in cells containing high NQO1 levels. We therefore tested the hypothesis
      that 5-methoxy-1,2-dimethyl-3-[(4-nitrophenoxy)methyl]indole-4,7-dione (ES936), a
      specific mechanism-based inhibitor of NQO1, would be an effective agent for the
      treatment of pancreatic tumors. The human pancreatic tumor cell lines BxPC-3 and
      MIA PaCa-2 contain high levels of NQO1 activity and protein as verified by
      immunoblot and immunocytochemical staining of human pancreatic tumor cells. ES936
      treatment inhibited NQO1 activity by >98% in MIA PaCa-2 and BxPC-3 cells. In
      addition, ES936 treatment induced growth inhibition [3-(4,5-dimethylthiazol-2-yl)
      2,5-diphenyltetrazolium bromide assay] in MIA PaCa-2 and BxPC-3 cells with an
      IC(50) of 108 and 365 nmol/L, respectively. Treatment of MIA PaCa-2 cells with
      ES936 also inhibited the ability of these cells to form colonies and grow in soft
      agar in a dose-dependent manner. Treatment of mice carrying MIA PaCa-2 xenograft
      tumors with ES936 resulted in a significant difference in growth rates in ES936
      treated and DMSO-treated (control) tumors. Our data did not show an increase in
      either intracellular superoxide production or oxygen consumption after treatment
      of cells with ES936, contrary to the effects seen with dicumarol. In summary,
      mechanism-based inhibitors of NQO1, such as ES936, may be useful therapeutic
      agents for the treatment of pancreatic cancer, although the underlying mechanism
      seems to be independent of superoxide generation.

PMID- 16891457
TI  - A new generation of anticancer, drug-loaded, colloidal vectors reverses multidrug
      resistance in glioma and reduces tumor progression in rats.
AB  - By focusing on rat glioma, we elucidated whether new lipid nanocapsules (LNC)
      were able to improve anticancer hydrophobic drug bioavailability while also
      overcoming multidrug resistance. Blank LNCs and LNCs loaded with the
      antineoplastic agent paclitaxel were formulated by an emulsion inversion phase
      process. Expression of efflux pumps by rat glioma cells was assessed by reverse
      transcription-PCR, Western blot, and immunohistochemistry, and their activity was
      followed using the tracer (99)Tc(m)-methoxyisobutylisonitrile. Modalities of LNC
      action were addressed by using confocal microscopy detection of fluorescently
      labeled LNCs, fluorescence-activated cell sorting, high-performance liquid
      chromatography measurement of paclitaxel release, and analysis of tumor cell
      growth. This revealed an interaction between LNCs and efflux pumps that resulted
      in an inhibition of multidrug resistance in glioma cells, both in culture and in
      cell implants in animals. LNCs were able to target the intracellular compartment
      of glioma cells, a mechanism that was abrogated by using intracellular
      cholesterol inhibitors but not by clathrin-coated pit or caveolae uptake
      inhibitors. This result can be correlated to the LNC inhibitory effects on efflux
      pump activity that is itself known to be stimulated by intracellular cholesterol.
      In parallel, we showed that paclitaxel-loaded LNCs were active reservoirs from
      which paclitaxel could be released. Finally, we established that paclitaxel
      loaded LNCs were more efficient than the commercially available paclitaxel
      formulation (Taxol) for clinical use, thus reducing tumor expansion in vitro and
      in vivo. Considering the physiologically compatible nature of LNC excipients,
      these data may represent an important step towards the development of new
      clinical therapeutic strategies against cancers.

PMID- 16891458
TI  - Mannosylated chitosan nanoparticle-based cytokine gene therapy suppressed cancer
      growth in BALB/c mice bearing CT-26 carcinoma cells.
AB  - Cancer immunotherapy relies on the ability of the immune system to destroy tumor
      cells selectively and to elicit a long-lasting memory of such activity.
      Interleukin-12 (IL-12) is an immunomodulatory cytokine produced primarily by
      antigen-presenting cells, which play an important role in promoting Th1-type
      immune response and cell-mediated immunity. To augment the antitumor immune
      action by in vivo IL-12 gene delivery, mannosylated chitosan (MC) was prepared to
      induce mannose receptor-mediated endocytosis of IL-12 gene directly into
      dendritic cells which reside within the tumor. Upon characterization, MC was
      proven to be suitable for IL-12 gene delivery due to good physicochemical
      properties and low cytotoxicity. In addition, MC exhibited much enhanced IL-12
      gene transfer efficiency to dendritic cells rather than chitosan itself in terms
      of the induction of murine IL-12 p70 and murine IFN-gamma. In animal studies,
      intratumoral injection of MC/plasmid encoding murine IL-12 complex into BALB/c
      mice bearing CT-26 carcinoma cells clearly suppressed tumor growth and
      angiogenesis, and significantly induced cell cycle arrest and apoptosis.
      Therefore, this study provides a new MC-mediated cytokine gene delivery system
      for cancer immunotherapy.

PMID- 16891459
TI  - Blockade of transforming growth factor-{beta} signaling in tumor-reactive CD8(+)
      T cells activates the antitumor immune response cycle.
AB  - Transforming growth factor-beta (TGF-beta) is a potent immunosuppressant.
      Overproduction of TGF-beta by tumor cells leads to evasion of host immune
      surveillance and tumor progression. Results of our early studies showed that
      adoptive transfer of tumor-reactive, TGF-beta-insensitive CD8(+) T cells into
      immunocompetent mice was able to eradicate lung metastasis of mouse prostate
      cancer. The present study was conducted with three objectives. (a) We tested if
      this technology could be applied to the treatment of solid xenograft tumors in
      allogeneic immunodeficient hosts. (b) We determined relevant variables in the
      tumor microenvironment with the treatment. (c) We tested if immune cells other
      than CD8(+) T cells were required for the antitumor effect. Mouse prostate cancer
      cells, TRAMP-C2 of the C57BL/6 strain, grown in immunodeficient allogeneic hosts
      of BALB/c strain, were used as a xenograft model. Tumor-reactive CD8(+) T cells
      from C57BL/6 mice were isolated, expanded ex vivo, and rendered insensitive to
      TGF-beta by introducing a dominant-negative TGF-beta type II receptor vector.
      Seven days following s.c. injection of TRAMP-C2 cells (5 x 10(5)) into the flank
      of male BALB/c-Rag1(-/-) mice, tumor-reactive, TGF-beta-insensitive CD8(+) T
      cells (1.5 x 10(7)) were transferred with and without the cotransfer of an equal
      number of CD8-depleted splenocytes from C57BL/6 donors. Naive CD8(+) T cells or
      green fluorescent protein-empty vector-transfected tumor-reactive CD8(+) T cells
      were transferred as controls. Forty days following the transfer, the average
      tumor weight in animals that received cotransfer of tumor-reactive, TGF-beta
      insensitive CD8(+) T cells and CD8-depleted splenocytes was at least 50% less
      than that in animals of all other groups (P < 0.05). Tumors in animals of the
      former group showed a massive infiltration of CD8(+) T cells. This was associated
      with secretion of relevant cytokines, decreased tumor proliferation, reduced
      angiogenesis, and increased tumor apoptosis. Based on these results, we
      postulated a concept of antitumor immune response cycle in tumor immunology.

PMID- 16891460
TI  - The effects of the oral, pan-VEGF-R kinase inhibitor CEP-7055 and chemotherapy in
      orthotopic models of glioblastoma and colon carcinoma in mice.
AB  - CEP-7055, a fully synthetic, orally active N,N-dimethylglycine ester of CEP-5214,
      a C3-(isopropylmethoxy)-fused pyrrolocarbazole with potent pan-vascular
      endothelial growth factor receptor (VEGFR) kinase inhibitory activity, has
      recently completed phase I clinical trials in cancer patients. These studies
      evaluated the antitumor efficacy of CEP-7055 using orthotopic models of
      glioblastoma and colon carcinoma in combination with temozolomide, and irinotecan
      and oxaliplatin, respectively, for their effects on primary and metastatic tumor
      burden and median survival. Chronic administration of CEP-7055 (23.8 mg/kg/dose)
      and temozolomide resulted in improvement of median survival of nude mice bearing
      orthotopic human glioblastoma xenografts compared with temozolomide alone (261
      versus 192 days, respectively; P < or = 0.02). Reductions in neurologic
      dysfunction, brain edema, hemorrhage, and intratumoral microvessel density (CD34
      staining) were observed in glioma-bearing mice receiving CEP-7055 alone,
      temozolomide alone, and the combination of CEP-7055 and temozolomide relative to
      vehicle and to temozolomide monotherapy. The administration of CEP-7055 in
      combination with irinotecan (20 mg/kg/dose i.p. x 5 days), and to a lesser degree
      with oxaliplatin (10 mg/kg/dose i.v.), showed reductions on primary colon
      carcinoma and hepatic metastatic burden in the CT-26 tumor model relative to that
      achieved by irinotecan and oxaliplatin monotherapy. These data show the
      significant efficacy and tolerability of optimal efficacious doses of CEP-7055
      when given in combination with temozolomide and irinotecan relative to
      monotherapy with these cytotoxic agents in preclinical orthotopic glioma and
      colon carcinoma models and lend support for the use of these treatment regimens
      in a clinical setting in patients with glioblastoma and colon carcinoma.

PMID- 16891461
TI  - Effect of an epidermal growth factor receptor tyrosine kinase inhibitor on actin
      remodeling in an in vitro bladder cancer carcinogenesis model.
AB  - Alteration of actin remodeling is a marker of malignant-associated field defect
      and a potential surrogate biomarker for chemoprevention trials. We tested
      erlotinib, a specific tyrosine kinase inhibitor of epidermal growth factor
      receptor (EGFR), on actin remodeling in a bladder carcinogenic model consisting
      of untransformed HUC-PC cells and transformed MC-T11 cells, both derived from the
      same normal human urothelial clone immortalized by SV40. Erlotinib had a
      selective growth inhibitory and actin remodeling effect on MC-T11 cells over HUC
      PC cells, as examined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide assay and immunofluorescence labeling with laser scan cytometer analysis,
      respectively. The IC(50) of untransformed HUC-PC cells was significantly higher
      than that of transformed MC-T11 cells (P < 0.05, t test). The actin remodeling
      effect was more prominent at lower dosage levels (1/8-1/4 of IC(50)), which was
      accompanied by an increased cell adhesion and decreased motility. At higher
      dosage levels (1/2 of IC(50)), erlotinib induced a decreased adhesion and anoikis
      (detachment-associated apoptosis). The transformed MC-T11, but not HUC-PC, showed
      a weak constitutive EGFR phosphorylation activity, which was inhibited by
      erlotinib in a dose-response manner. However, on epidermal growth factor
      stimulation, both cell lines showed a similar dose-response inhibitory effect on
      phosphorylated EGFR and mitogen-activated protein kinase (MAPK; P44/P42)
      activities, and MAPK inhibitor PD98059 showed no specific effect on erlotinib
      induced actin remodeling, suggesting that pathways other than MAPK (P44/P42) may
      be responsible for erlotinib-induced actin remodeling. The findings provide
      evidence to support erlotinib-based bladder cancer chemoprevention and using
      actin remodeling as a marker for erlotinib-based intervention trials.

PMID- 16891462
TI  - Identification of a lead small-molecule inhibitor of the Aurora kinases using a
      structure-assisted, fragment-based approach.
AB  - Aurora A and Aurora B are potential targets for anticancer drug development due
      to their roles in tumorigenesis and disease progression. To identify small
      molecule inhibitors of the Aurora kinases, we undertook a structure-based design
      approach that used three-dimensional structural models of the Aurora A kinase and
      molecular docking simulations of chemical entities. Based on these computational
      methods, a new generation of inhibitors derived from quinazoline and pyrimidine
      based tricyclic scaffolds were synthesized and evaluated for Aurora A kinase
      inhibitory activity, which led to the identification of 4-(6,7-dimethoxy-9H-1,3,9
      triaza-fluoren-4-yl)-piperazine-1-carbothioic acid [4-(pyrimidin-2-ylsulfamoyl)
      phenyl]-amide. The lead compound showed selectivity for the Aurora kinases when
      it was evaluated against a panel of diverse kinases. Additionally, the compound
      was evaluated in cell-based assays, showing a dose-dependent decrease in phospho
      histone H3 levels and an arrest of the cell cycle in the G(2)-M fraction.
      Although biological effects were observed only at relatively high concentrations,
      this chemical series provides an excellent starting point for drug optimization
      and further development.

PMID- 16891463
TI  - SU14813: a novel multiple receptor tyrosine kinase inhibitor with potent
      antiangiogenic and antitumor activity.
AB  - Receptor tyrosine kinases (RTK), such as vascular endothelial growth factor
      receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), stem cell
      factor receptor (KIT), and fms-like tyrosine kinase 3 (FLT3), are expressed in
      malignant tissues and act in concert, playing diverse and major roles in
      angiogenesis, tumor growth, and metastasis. With the exception of a few
      malignancies, seemingly driven by a single genetic mutation in a signaling
      protein, most tumors are the product of multiple mutations in multiple aberrant
      signaling pathways. Consequently, simultaneous targeted inhibition of multiple
      signaling pathways could be more effective than inhibiting a single pathway in
      cancer therapies. Such a multitargeted strategy has recently been validated in a
      number of preclinical and clinical studies using RTK inhibitors with broad target
      selectivity. SU14813, a small molecule identified from the same chemical library
      used to isolate sunitinib, has broad-spectrum RTK inhibitory activity through
      binding to and inhibition of VEGFR, PDGFR, KIT, and FLT3. In cellular assays,
      SU14813 inhibited ligand-dependent and ligand-independent proliferation,
      migration, and survival of endothelial cells and/or tumor cells expressing these
      targets. SU14813 inhibited VEGFR-2, PDGFR-beta, and FLT3 phosphorylation in
      xenograft tumors in a dose- and time-dependent fashion. The plasma concentration
      required for in vivo target inhibition was estimated to be 100 to 200 ng/mL. Used
      as monotherapy, SU14813 exhibited broad and potent antitumor activity resulting
      in regression, growth arrest, or substantially reduced growth of various
      established xenografts derived from human or rat tumor cell lines. Treatment in
      combination with docetaxel significantly enhanced both the inhibition of primary
      tumor growth and the survival of the tumor-bearing mice compared with
      administration of either agent alone. In summary, SU14813 inhibited target RTK
      activity in vivo in association with reduction in angiogenesis, target RTK
      mediated proliferation, and survival of tumor cells, leading to broad and potent
      antitumor efficacy. These data support the ongoing phase I clinical evaluation of
      SU14813 in advanced malignancies.

PMID- 16891464
TI  - Enzastaurin (LY317615), a protein kinase Cbeta inhibitor, inhibits the AKT
      pathway and induces apoptosis in multiple myeloma cell lines.
AB  - Enzastaurin (LY317615), an acyclic bisindolylmaleimide, is an oral inhibitor of
      the protein kinase Cbeta isozyme. The objective of this study was to assess the
      efficacy of enzastaurin in inducing apoptosis in multiple myeloma (MM) cell lines
      and to investigate possible mechanisms of apoptosis. Cell proliferation assays
      were done on a variety of MM cell lines with unique characteristics
      (dexamethasone sensitive, dexamethasone resistant, chemotherapy sensitive, and
      melphalan resistant). The dexamethasone-sensitive MM.1S cell line was used to
      further assess the effect of enzastaurin in the presence of dexamethasone,
      insulin-like growth factor-I (IGF-I), interleukin-6, and the pan-specific caspase
      inhibitor ZVAD-fmk. Enzastaurin increased cell death in all cell lines at
      clinically significant low micromolar concentrations (1-3 micromol/L) after 72
      hours of treatment. Dexamethasone and enzastaurin were shown to have an additive
      effect on MM.1S cell death. Although IGF-I blocked the effect of 1 micromol/L
      enzastaurin, IGF-I did not abrogate cell death induced with 3 mumol/L
      enzastaurin. Moreover, enzastaurin-induced cell death was not affected by
      interleukin-6 or ZVAD-fmk. GSK3beta phosphorylation, a reliable pharmacodynamic
      marker for enzastaurin activity, and AKT phosphorylation were both decreased with
      enzastaurin treatment. These data indicate that enzastaurin induces apoptosis in
      MM cell lines in a caspase-independent manner and that enzastaurin exerts its
      antimyeloma effect by inhibiting signaling through the AKT pathway.

PMID- 16891465
TI  - AGRO100 inhibits activation of nuclear factor-kappaB (NF-kappaB) by forming a
      complex with NF-kappaB essential modulator (NEMO) and nucleolin.
AB  - AGRO100, also known as AS1411, is an experimental anticancer drug that recently
      entered human clinical trials. It is a member of a novel class of
      antiproliferative agents known as G-rich oligonucleotides (GRO), which are non
      antisense, guanosine-rich phosphodiester oligodeoxynucleotides that form stable G
      quadruplex structures. The biological activity of GROs results from their binding
      to specific cellular proteins as aptamers. One important target protein of GROs
      has been previously identified as nucleolin, a multifunctional protein expressed
      at high levels by cancer cells. Here, we report that AGRO100 also associates with
      nuclear factor-kappaB (NF-kappaB) essential modulator (NEMO), which is a
      regulatory subunit of the inhibitor of kappaB (IkappaB) kinase (IKK) complex, and
      also called IKKgamma. In the classic NF-kappaB pathway, the IKK complex is
      required for phosphorylation of IkappaBalpha and subsequent activation of the
      transcription factor NF-kappaB. We found that treatment of cancer cells with
      AGRO100 inhibits IKK activity and reduces phosphorylation of IkappaBalpha in
      response to tumor necrosis factor-alpha stimulation. Using a reporter gene assay,
      we showed that AGRO100 blocks both tumor necrosis factor-alpha-induced and
      constitutive NF-kappaB activity in human cancer cell lines derived from cervical,
      prostate, breast, and lung carcinomas. In addition, we showed that, in AGRO100
      treated cancer cells, NEMO is coprecipitated by nucleolin, indicating that both
      proteins are present in the same complex. Our studies suggest that abrogation of
      NF-kappaB activity may contribute to the anticancer effects of AGRO100 and that
      nucleolin may play a previously unknown role in regulating the NF-kappaB pathway.

PMID- 16891466
TI  - The determinants of sensitivity and acquired resistance to gemcitabine differ in
      non-small cell lung cancer: a role of ABCC5 in gemcitabine sensitivity.
AB  - We examined the expression levels of the multidrug resistance protein 5 (ABCC5)
      gene in non-small cell lung cancer (NSCLC) cell lines to clarify the relationship
      with the sensitivity to gemcitabine. The expression levels of ABCC5 were
      inversely correlated with gemcitabine sensitivity significantly (r = 0.628; P <
      0.01) in 17 NSCLC cells, whereas the expression of ABCC5 in the gemcitabine
      resistant NSCLC cell line H23/GEM-R was the same as that in parental NCI-H23
      cells. Treatment with the ABCC5 inhibitor zaprinast altered the sensitivity to
      gemcitabine in ABCC5-expressing NSCLC cells. In addition, decreasing the
      expression of ABCC5 by small interfering RNA altered the cytotoxicity to
      gemcitabine. These results indicate that modulation of ABCC5 activity could be
      used to increase the gemcitabine sensitivity in NSCLC. Previously, we found a
      decreased expression of deoxycytidine kinase in H23/GEM-R cells, and further
      investigation in this study showed an increased expression of ribonucleotide
      reductase subunit 1 in H23/GEM-R cells. We therefore also examined the effect of
      modifying the expression of both genes on gemcitabine resistance. We found that
      using small interfering RNA to decrease the expression of ribonucleotide
      reductase subunit 1 resulted in a decreased resistance to gemcitabine in H23/GEM
      R cells. Furthermore, pretreatment with pemetrexed resulted in an increased
      deoxycytidine kinase expression concomitant with the alteration of the resistance
      to gemcitabine in H23/GEM-R cells. The determinants for sensitivity and the
      acquired resistance in gemcitabine are quite different; nonetheless, modification
      of these factors may increase the efficacy of gemcitabine in the treatment of
      NSCLC.

PMID- 16891467
TI  - Cyclohexylpiperazine derivative PB28, a sigma2 agonist and sigma1 antagonist
      receptor, inhibits cell growth, modulates P-glycoprotein, and synergizes with
      anthracyclines in breast cancer.
AB  - sigma Ligands have recently been shown to have cytotoxic activity, to induce
      ceramide-dependent/caspase-independent apoptosis, and to down-regulate P
      glycoprotein (P-gp) mRNA levels in some mouse and human models. In this study, we
      verified whether a mixed sigma(2) agonist/sigma(1) antagonist, PB28, was able to
      have antitumor activity and to enhance anthracycline efficacy in two human breast
      cancer cell lines, MCF7 and MCF7 ADR, both characterized by significant sigma(2)
      receptor expression, by high and low sigma(1) receptor expression, and low and
      high P-gp expression, respectively. In both cell lines, PB28 showed high sigma(2)
      receptor affinity and low sigma(1) receptor affinity; furthermore, it inhibited
      cell growth with a clear effect at 48 hours (IC(50) in nanomolar range), a
      consistent time exposure-independent increase of G(0)-G(1)-phase fraction (of
      approximately 20% of both cell lines) and caspase-independent apoptosis (15%
      increased after 1-day drug exposure). PB28 also reduced P-gp expression in a
      concentration- and time-dependent manner ( approximately 60% in MCF7 and 90% in
      MCF7 ADR). We showed also a strong synergism between PB28 and doxorubicin by
      adopting either simultaneous or sequential schedules of the two drugs. We suggest
      that this synergism could depend on PB28-induced increase of intracellular
      accumulation of doxorubicin ( approximately 50% in MCF7 and 75% in MCF7 ADR by
      flow cytometry analysis). In conclusion, we suggest that the sigma(2) agonist
      PB28 could be an interesting antitumor agent either in monotherapy or in
      combination with conventional drugs.

PMID- 16891468
TI  - Microsomal prostaglandin E synthase-1 regulates human glioma cell growth via
      prostaglandin E(2)-dependent activation of type II protein kinase A.
AB  - Dysregulation of enzymes involved in prostaglandin biosynthesis plays a critical
      role in influencing the biological behavior and clinical outcome of several
      tumors. In human gliomas, overexpression of cyclooxygenase-2 has been linked to
      increased aggressiveness and poor prognosis. In contrast, the role of
      prostaglandin E synthase in influencing the biological behavior of human gliomas
      has not been established. We report that constitutive expression of the
      microsomal prostaglandin E synthase-1 (mPGES-1) is associated with increased
      prostaglandin E(2) (PGE(2)) production and stimulation of growth in the human
      astroglioma cell line U87-MG compared with human primary astrocytes.
      Consistently, pharmacologic and genetic inhibition of mPGES-1 activity and
      expression blocked the release of PGE(2) from U87-MG cells and decreased their
      proliferation. Conversely, exogenous PGE(2) partially overcame the
      antiproliferative effects of mPGES-1 inhibition and stimulated U87-MG cell
      proliferation in the absence of mPGES-1 inhibitors. The EP2/EP4 subtype PGE(2)
      receptors, which are linked to stimulation of adenylate cyclase, were expressed
      in U87-MG cells to a greater extent than in human astrocytes. PGE(2) increased
      cyclic AMP levels and stimulated protein kinase A (PKA) activity in U87-MG cells.
      Treatment with a selective type II PKA inhibitor decreased PGE(2)-induced U87-MG
      cell proliferation, whereas a selective type I PKA inhibitor had no effect. Taken
      together, these results are consistent with the hypothesis that mPGES-1 plays a
      critical role in promoting astroglioma cell growth via PGE(2)-dependent
      activation of type II PKA.

PMID- 16891469
TI  - 15-Deoxy-Delta12,14-prostaglandin J(2) induces death receptor 5 expression
      through mRNA stabilization independently of PPARgamma and potentiates TRAIL
      induced apoptosis.
AB  - 15-Deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)), the terminal derivative of
      the PGJ series, is emerging as a potent antineoplastic agent among cyclopentenone
      prostaglandins derivatives and also known as the endogenous ligand of peroxisome
      proliferator-activated receptor gamma (PPARgamma). On the other hand, death
      receptor 5 (DR5) is a specific receptor for tumor necrosis factor-related
      apoptosis-inducing ligand (TRAIL), which is one of the most promising candidates
      for new cancer therapeutics. Here, we report that 15d-PGJ(2) induces DR5
      expression at both mRNA and protein levels, resulting in the synergistic
      sensitization of TRAIL-induced apoptosis in human neoplastic cells, such as
      Jurkat human leukemia cells or PC3 human prostate cancer cells. 15d-PGJ(2)
      significantly increased DR5 mRNA stability, whereas it did not activate DR5
      promoter activity. Synthetic PPARgamma agonists, such as pioglitazone or
      rosiglitazone, did not mimic the DR5-inducing effects of 15d-PGJ(2), and a potent
      PPARgamma inhibitor GW9662 failed to block DR5 induction by 15d-PGJ(2),
      suggesting PPARgamma-independent mechanisms. Cotreatment with 15d-PGJ(2) and
      TRAIL enhanced the sequential activation of caspase-8, caspase-10, caspase-9,
      caspase-3, and Bid. DR5/Fc chimera protein, zVAD-fmk pancaspase inhibitor, and
      caspase-8 inhibitor efficiently blocked the activation of these apoptotic signal
      mediators and the induction of apoptotic cell death enhanced by cotreatment with
      15d-PGJ(2) and TRAIL. Moreover, a double-stranded small interfering RNA targeting
      DR5 gene, which suppressed DR5 up-regulation by 15d-PGJ(2), significantly
      attenuated apoptosis induced by cotreatment with 15d-PGJ(2) and TRAIL. These
      results suggest that 15d-PGJ(2) is a potent sensitizer of TRAIL-mediated cancer
      therapeutics through DR5 up-regulation.

PMID- 16891470
TI  - The proteasome inhibitor NPI-0052 is a more effective inducer of apoptosis than
      bortezomib in lymphocytes from patients with chronic lymphocytic leukemia.
AB  - Proteasome inhibitors are potent inducers of apoptosis in isolated lymphocytes
      from patients with chronic lymphocytic leukemia (CLL). However, the reversible
      proteasome inhibitor bortezomib (PS-341; Velcade) did not display substantial
      antitumor activity in CLL patients. Here, we compared the effects of bortezomib
      and a new irreversible proteasome inhibitor (NPI-0052) on 20S chymotryptic
      proteasome activity and apoptosis in isolated CLL cells in vitro. Although their
      steady-state (3 hours) IC(50)s as proteasome inhibitors were similar, NPI-0052
      exerted its effects more rapidly than bortezomib, and drug washout experiments
      showed that short exposures to NPI-0052 resulted in sustained (> or =24 hours)
      20S proteasome inhibition, whereas 20S activity recovered in cells exposed to
      even 10-fold higher concentrations of bortezomib. Thus, brief (15 minutes) pulses
      of NPI-0052 were sufficient to induce substantial apoptosis in CLL cells, whereas
      longer exposure times (> or =8 hours) were required for commitment to apoptosis
      in cells exposed to equivalent concentrations of bortezomib. Commitment to
      apoptosis seemed to be related to caspase-4 activation, in that cells exposed to
      bortezomib or NPI-0052 could be saved from death by addition of a selective
      caspase-4 inhibitor up to 8 hours after drug exposure. Our results show that NPI
      0052 is a more effective proapoptotic agent than bortezomib in isolated CLL cells
      and suggest that the chemical properties of NPI-0052 might also make it an
      effective therapeutic agent in CLL patients.

PMID- 16891471
TI  - Multiple mechanisms underlie resistance of leukemia cells to Apo2 Ligand/TRAIL.
AB  - Targeting death receptors with tumor necrosis factor-related apoptosis-inducing
      ligand (TRAIL) has the remarkable potential to selectively kill malignant cells
      whereas normal cells are largely unaffected by this treatment. However, some
      tumor cells, including leukemia cells, exhibit resistance to this molecule. To
      investigate the basis for resistance of leukemia cells to the zinc-bound form of
      Apo2 ligand (Apo2L)/TRAIL, which is currently being evaluated in clinical trial,
      we isolated several resistant HL60 clones from parental HL60 cells by selection
      using the recombinant Apo2L/TRAIL. Differing resistance mechanisms were
      identified and characterized in these Apo2L/TRAIL-resistant clones. In one case,
      the level of the cell-surface death receptor DR4, but not DR5, was significantly
      decreased. However, these cells did undergo apoptosis in response to another form
      of recombinant TRAIL, histidine-tagged TRAIL, suggesting differing contributions
      of DR4 and DR5 in the response to these two forms of TRAIL. In the case of other
      clones, expression of procaspase-8 protein was lost and this was associated with
      a novel Leu(22)-->Phe(22) point mutation in CASP-8 gene. These results show that
      cells within a given tumor can have widely distinct mechanisms underlying
      resistance to Apo2L/TRAIL.

PMID- 16891472
TI  - Ratiometric dosing of anticancer drug combinations: controlling drug ratios after
      systemic administration regulates therapeutic activity in tumor-bearing mice.
AB  - Anticancer drug combinations can act synergistically or antagonistically against
      tumor cells in vitro depending on the ratios of the individual agents comprising
      the combination. The importance of drug ratios in vivo, however, has heretofore
      not been investigated, and combination chemotherapy treatment regimens continue
      to be developed based on the maximum tolerated dose of the individual agents. We
      systematically examined three different drug combinations representing a range of
      anticancer drug classes with distinct molecular mechanisms
      (irinotecan/floxuridine, cytarabine/daunorubicin, and cisplatin/daunorubicin) for
      drug ratio-dependent synergy. In each case, synergistic interactions were
      observed in vitro at certain drug/drug molar ratio ranges (1:1, 5:1, and 10:1,
      respectively), whereas other ratios were additive or antagonistic. We were able
      to maintain fixed drug ratios in plasma of mice for 24 hours after i.v. injection
      for all three combinations by controlling and overcoming the inherent dissimilar
      pharmacokinetics of individual drugs through encapsulation in liposomal carrier
      systems. The liposomes not only maintained drug ratios in the plasma after
      injection, but also delivered the formulated drug ratio directly to tumor tissue.
      In vivo maintenance of drug ratios shown to be synergistic in vitro provided
      increased efficacy in preclinical tumor models, whereas attenuated antitumor
      activity was observed when antagonistic drug ratios were maintained. Fixing
      synergistic drug ratios in pharmaceutical carriers provides an avenue by which
      anticancer drug combinations can be optimized prospectively for maximum
      therapeutic activity during preclinical development and differs from current
      practice in which dosing regimens are developed empirically in late-stage
      clinical trials based on tolerability.

PMID- 16891473
TI  - Clioquinol and docosahexaenoic acid act synergistically to kill tumor cells.
AB  - Clioquinol, an 8-hydroxyquinoline derivative (5-chloro-7-iodo-8-hydroxyquinoline)
      with antimicrobial properties, has recently been found to have cytotoxic activity
      towards human cancer cell lines at concentrations achieved by oral
      administration. This study was initiated to determine whether clioquinol could
      potentiate the antitumor effects of two drugs, doxorubicin and docosahexaenoic
      acid (DHA), believed to act in part via the generation of reactant oxidant
      species. At low micromolar concentrations, clioquinol had little effect upon cell
      viability and did not potentiate doxorubicin's cytotoxicity. Clioquinol
      significantly enhanced DHA's cytotoxic effects, an interaction that was shown to
      be synergistic by isobolographic analysis. Clioquinol exhibited a synergistic
      interaction with DHA in reducing nuclear factor-kappaB activity and inducing
      apoptosis, and the combination reduced the level of several molecules that
      promote cell survival, including Akt, p65, and Bcl-2. Interestingly, clioquinol
      neither induced lipid peroxidation itself nor increased peroxidation brought
      about by the addition of DHA. However, when cells were pretreated with
      antioxidant vitamin E, the synergism of clioquinol and DHA was blocked,
      indicating the essential role of lipid peroxidation for their action. These
      findings reveal a novel antitumor drug combination that synergistically targets
      major cell survival signaling pathways.

PMID- 16891474
TI  - Inorganic selenium sensitizes prostate cancer cells to TRAIL-induced apoptosis
      through superoxide/p53/Bax-mediated activation of mitochondrial pathway.
AB  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been shown to
      induce apoptosis in prostate cancer cells through DR4 and DR5 death receptors,
      but not in normal prostate cells, which do not express these receptors.
      Therefore, TRAIL has excellent potential to be a selective prostate cancer
      therapeutic agent with minimal toxic side effects. However, prostate cancer
      cells, as many other cancer types, develop resistance to TRAIL, and the
      underlying molecular mechanisms require further investigation. We hypothesize
      that selenium may sensitize TRAIL-resistant cells to undergo caspase-mediated
      apoptosis and increase therapeutic efficacy. Here, we report that TRAIL signaling
      in LNCaP prostate cancer cells stalled at downstream of caspase-8 and BID
      cleavage, as indicated by the lack of Bax translocation into mitochondria, and no
      subsequent activation of the caspase-9 cascade. Selenite induced a rapid
      generation of superoxide and p53 Ser(15) phosphorylation and increased Bax
      abundance and translocation into the mitochondria. Selenite and TRAIL combined
      treatment led to synergistic increases of Bax abundance and translocation into
      mitochondria, loss of mitochondrial membrane potential, cytochrome c release, and
      cleavage activation of caspase-9 and caspase-3. Inactivating p53 with a dominant
      negative mutant abolished apoptosis without affecting superoxide generation,
      whereas a superoxide dismutase mimetic agent blocked p53 activation, Bax
      translocation to mitochondria, cytochrome c release, and apoptosis induced by
      selenite/TRAIL. In support of Bax as a crucial target for cross-talk between
      selenite and TRAIL pathways, introduction of Bax into p53 mutant DU145 cells
      enabled selenite to sensitize these cells for TRAIL-induced apoptosis. Taken
      together, the results indicate that selenite induces a rapid superoxide burst and
      p53 activation, leading to Bax up-regulation and translocation into mitochondria,
      which restores the cross-talk with stalled TRAIL signaling for a synergistic
      caspase-9/3 cascade-mediated apoptosis execution.

PMID- 16891475
TI  - Sequence-dependent inhibition of human colon cancer cell growth and of
      prosurvival pathways by oxaliplatin in combination with ZD6474 (Zactima), an
      inhibitor of VEGFR and EGFR tyrosine kinases.
AB  - To date, clinical studies combining the new generation of targeted therapies and
      chemotherapy have had mixed results. Preclinical studies can be used to identify
      potential antagonism/synergy between certain agents, with the potential to
      predict the most efficacious combinations for further investigation in the
      clinical setting. In this study, we investigated the sequence-dependent
      interactions of ZD6474 with oxaliplatin in two human colon cell lines in vitro.
      We evaluated the in vitro antitumor activity of ZD6474, an inhibitor of vascular
      endothelial growth factor receptor (VEGFR), epidermal growth factor receptor
      (EGFR) and RET tyrosine kinase activity, and oxaliplatin using three combination
      schedules: ZD6474 before oxaliplatin, oxaliplatin before ZD6474, and concurrent
      exposure. Cell proliferation studies showed that treatment with oxaliplatin
      followed by ZD6474 was highly synergistic, whereas the reverse sequence was
      clearly antagonistic as was concurrent exposure. Oxaliplatin induced a G(2)-M
      arrest, which was antagonized if the cells were previously or concurrently
      treated with ZD6474. ZD6474 enhanced oxaliplatin-induced apoptosis but only when
      added after oxaliplatin. The sequence-dependent antitumor effects appeared, in
      part, to be based on modulation of compensatory prosurvival pathways. Thus,
      expression of total and active phosphorylated EGFR, as well as AKT and
      extracellular signal-regulated kinase, was markedly increased by oxaliplatin.
      This increase was blocked by subsequent treatment with ZD6474. Furthermore, the
      synergistic sequence resulted in reduced expression of insulin-like growth factor
      I receptor and a marked reduction in secretion of vascular endothelial growth
      factor protein. ZD6474 in combination with oxaliplatin has synergistic
      antiproliferative properties in human colorectal cancer cell lines in vitro when
      oxaliplatin is administered before ZD6474.

PMID- 16891477
TI  - Mass spectrometry for species or strain identification after culture or without
      culture: Past, present, and future.

PMID- 16891476
TI  - Assessment of gefitinib- and CI-1040-mediated changes in epidermal growth factor
      receptor signaling in HuCCT-1 human cholangiocarcinoma by serial fine needle
      aspiration.
AB  - One specific limitation to the clinical development of targeted cancer
      therapeutics is the lack of well-validated pharmacodynamic markers. Such tools
      might conceivably provide a framework within which to better evaluate the
      selection of specific molecules as therapeutic targets. Nevertheless, the
      practical application of this hypothesis in clinical development remains elusive.
      In this study, we present a minimally invasive pharmacodynamic assay for
      monitoring therapy-mediated changes in the activity of target signaling pathways
      by using fine needle aspiration (FNA) samples and quantitative ELISA methods. To
      this end, we used the HuCCT-1 cholangiocarcinoma cell line treated with gefitinib
      (ZD1839, Iressa), a selective blocker of the epidermal growth factor receptor
      (EGFR), and CI-1040, a selective inhibitor of the mitogen extracellular regulated
      kinase [mitogen-activated protein/extracellular signal-regulated kinase (ERK)
      kinase 1/2]. HuCCT-1 cells were resistant to gefitinib and CI-1040 alone but
      susceptible to the combination of these drugs in vitro and in vivo. This effect
      was associated with a greater inhibition of ERK1/2 activation, a downstream
      mediator in the EGFR-mitogen-activated protein/ERK kinase pathway. Using this
      model, we sought to assess whether FNA-obtained tumor biopsies could be used to
      measure signaling pathway activation. Cellular extracts prepared from FNA samples
      yielded adequately cellular, high-quality samples to assess therapy-mediated
      changes in EGFR and ERK1/2 phosphorylation by Western blotting and quantitative
      ELISA assays. Treatment with gefitinib alone effectively inhibited EGFR
      activation but failed to block ERK1/2 phosphorylation and tumor growth. Blocking
      was achieved by the addition of CI-1040 to the treatment regimen. These results
      show that the combination of serial FNA sampling with highly sensitive
      quantitative ELISA assays permits assessment of therapy-mediated changes in
      signaling pathways, which correlate well with antitumor effects. This assay is
      simple to implement and broadly applicable to diverse tumor types in clinical
      studies with cancer patients and may be useful in the development of targeted
      anticancer agents.

PMID- 16891478
TI  - Multicenter comparison of nucleic acid extraction methods for detection of severe
      acute respiratory syndrome coronavirus RNA in stool specimens.
AB  - The emergence of a novel coronavirus (CoV) as the cause of severe acute
      respiratory syndrome (SARS) catalyzed the development of rapid diagnostic tests.
      Stool samples have been shown to be appropriate for diagnostic testing for SARS
      CoV, although it has been recognized to be a heterogeneous and difficult sample
      that contains amplification inhibitors. Limited information on the efficiency of
      extraction methods for the purification and concentration of SARS CoV RNA from
      stool samples is available. Our study objectives were to determine the optimal
      extraction method for SARS CoV RNA detection and to examine the effect of
      increased specimen volume for the detection of SARS CoV RNA in stool specimens.
      We conducted a multicenter evaluation of four automated and four manual
      extraction methods using dilutions of viral lysate in replicate mock stool
      samples, followed by quantitation of SARS CoV RNA using real-time reverse
      transcriptase PCR. The sensitivities of the manual methods ranged from 50% to
      100%, with the Cortex Biochem Magazorb method, a magnetic bead isolation method,
      allowing detection of all 12 positive samples. The sensitivities of the automated
      methods ranged from 75% to 100%. The bioMerieux NucliSens automated extractor and
      miniMag extraction methods each had a sensitivity of 100%. Examination of the
      copy numbers detected and the generation of 10-fold dilutions of the extracted
      material indicated that a number of extraction methods retained inhibitory
      substances that prevented optimal amplification. Increasing the volume of sample
      input did improve detection. This information could be useful for the extraction
      of other RNA viruses from stool samples and demonstrates the need to evaluate
      extraction methods for different specimen types.

PMID- 16891479
TI  - Molecular epidemiology of Neisseria gonorrhoeae in Amsterdam, The Netherlands,
      shows distinct heterosexual and homosexual networks.
AB  - Molecular typing, added to epidemiological data, can better identify transmission
      patterns of gonorrhea in Western countries, where the incidence has recently been
      rising. From September 2002 to September 2003, patients with a laboratory
      confirmed diagnosis of gonorrhea at the Clinic for Sexually Transmitted
      Infections in Amsterdam, The Netherlands, were subjected to a questionnaire
      pertaining to sexual risk behavior and sexual partners in the 6 months prior to
      the diagnosis. The Neisseria gonorrhoeae isolates were all genotyped using PCR
      restriction fragment length polymorphism of the porin and opacity genes. All
      patients with a completed questionnaire and genotyped isolates were included in
      the study. We obtained 885 N. gonorrhoeae isolates from 696 patients that
      revealed 88 clusters and 46 unique genotypes. Patients infected at multiple
      anatomical sites with one or more strains and patients infected several times
      during the study period were shown to pursue high-risk sexual behavior and were
      considered core groups. There were 11 clusters of > or =20 patients; in seven
      clusters, 81% to 100% of patients were men who have sex with men (MSM), three
      clusters contained 87 to 100% heterosexual men and women, and one cluster was
      formed by equal proportions of MSM and heterosexual male and female patients.
      However, the various clusters differed in characteristics such as types of
      coinfections, numbers of sexual partners, Internet use to seek sexual partners,
      and locations of sexual encounters. Molecular epidemiology of gonococcal isolates
      in Amsterdam revealed core groups and clusters of MSM and heterosexual patients
      that probably indicate distinct transmission networks.

PMID- 16891480
TI  - Sensitive, seminested PCR amplification of VP1 sequences for direct
      identification of all enterovirus serotypes from original clinical specimens.
AB  - A reverse transcription-seminested PCR (RT-snPCR) assay was developed for the
      detection and identification of enterovirus (EV) RNA in clinical specimens. Three
      conserved protein motifs were identified by aligning the VP3 and VP1 sequences of
      prototype EV strains. Consensus degenerate primers were designed from a conserved
      VP3 motif and a distal VP1 motif for the first PCR. Consensus-degenerate hybrid
      oligonucleotide primers were designed from an internal VP1 motif and used with
      the same distal VP1 motif for the second, seminested PCR step. The primers were
      designed for broad target specificity and amplified all recognized and proposed
      EV serotypes and other antigenic variant strains tested. The VP1 RT-snPCR assay
      was slightly more sensitive than our in-house EV 5' nontranslated region RT-snPCR
      assay, detecting as few as 10 RNA copies per reaction. As an example application,
      the VP1 RT-snPCR assay was used to identify EVs in clinical specimens. A product
      of the expected size was successfully amplified and sequenced from cerebrospinal
      fluid; serum; stool suspensions; and nasopharyngeal, eye, and rectal swab
      specimens, allowing unambiguous identification of the infecting virus in all
      cases. The VP1 sequences derived from the RT-snPCR products allow rapid
      phylogenetic and molecular epidemiologic analysis of strains circulating during
      the EV season and comparison with EV sequences from past seasons or from
      different locations around the world.

PMID- 16891481
TI  - Increasing appearance of reassortant influenza B virus in Taiwan from 2002 to
      2005.
AB  - Genetic and antigenic analyses of influenza B virus field strains isolated in
      Taiwan from 1998 to 2005 were performed. To investigate the molecular evolution
      of influenza B viruses, sequence analysis of the hemagglutinin (HA1 subunit) and
      neuraminidase genes was performed. All influenza B viruses isolated between 1998
      and 2000 belonged to the B/Yamagata/16/88 lineage. The B/Victoria/2/87 lineage,
      which was cocirculating with the Yamagata lineage, was identified in Taiwan in
      March 2001. Concurrently, there was an increasing prevalence of this lineage in
      many parts of the world, including North America and Europe, during the 2001-2002
      season. Since 2002, genetic reassortants of influenza B virus with the Victoria
      lineage of hemagglutinin and the Yamagata lineage of neuraminidase have been
      found at a rate of 46%. Therefore, in 2002, at least three sublineages of
      influenza B virus strains, the B/Shanghai/361/2002-like strain (Yamagata
      lineage), the B/Hong Kong/330/01-like strain (Victoria lineage), and the B/Hong
      Kong/1351/02-like strain (B reassortant lineage), were identified in Taiwan. The
      results showed that genetically distinct lineages can cocirculate in the
      population and that the reassortment among these strains plays a role in
      generating the genetic diversity of influenza B viruses. Interestingly, from
      January to April 2005, B reassortant viruses became dominant (73%) in Taiwan,
      which indicated that a mismatch had occurred between the influenza B vaccine
      strain recommended for the 2004-2005 season in the Northern hemisphere by the
      World Health Organization and the epidemic strain.

PMID- 16891482
TI  - Enhanced reverse transcription-PCR assay for detection of norovirus genogroup I.
AB  - We have developed a one-tube reverse transcription (RT)-PCR method using the real
      time TaqMan PCR system for the detection of norovirus genogroup I (NV GGI). By
      introduction of a novel probe based on locked nucleic acid technology, we
      enhanced the sensitivity of the assay compared to those of conventional TaqMan
      probes. The sensitivity of the NV GGI RT-PCR was determined by probit analysis
      with defined RNA standards and quantified norovirus isolates to 711 copies/ml
      (95% detection limit). In order to detect PCR inhibition, we included a
      heterologous internal control (IC) system based on phage MS2. This internally
      controlled RT-PCR was tested on different real-time PCR platforms, LightCycler,
      Rotorgene, Mastercycler EP realplex, and ABI Prism. Compared to the assay without
      an IC, the duplex RT-PCR exhibited no reduction in sensitivity in clinical
      samples. In combination with an established NV GGII real-time RT-PCR, we used the
      novel assay in a routine assay for diagnosis of clinical and food-borne norovirus
      infection. We applied this novel assay to analyze outbreaks of nonbacterial acute
      gastroenteritis. Norovirus of GGI was detected in these outbreaks. Sequence and
      similarity plot analysis of open reading frame 1 (ORF1) and ORF2 showed two
      genotypes, GGI/2 and GGI/4, in semiclosed communities.

PMID- 16891483
TI  - Therapeutic failures of antibiotics used to treat macrolide-susceptible
      Streptococcus pyogenes infections may be due to biofilm formation.
AB  - Streptococcus pyogenes infections often fail to respond to antibiotic therapy,
      leading to persistent throat carriage and recurrent infections. Such failures
      cannot always be explained by the occurrence of antibiotic resistance
      determinants, and it has been suggested that S. pyogenes may enter epithelial
      cells to escape antibiotic treatment. We investigated 289 S. pyogenes strains
      isolated from different clinical sources to evaluate their ability to form
      biofilm as an alternative method to escape antibiotic treatment and host
      defenses. Up to 90% of S. pyogenes isolates, from both invasive and noninvasive
      infections, were able to form biofilm. Specific emm types, such as emm6, appeared
      to be more likely to produce biofilm, although variations within strains
      belonging to the same type might suggest biofilm formation to be a trait of
      individual strains rather than a general attribute of a serotype. Interestingly,
      erythromycin-susceptible isolates formed a significantly thicker biofilm than
      resistant isolates (P < 0.05). Among resistant strains, those carrying the erm
      class determinants formed a less organized biofilm than the mef(A)-positive
      strains. Also, prtF1 appeared to be negatively associated with the ability to
      form biofilm (P < 0.01). Preliminary data on a selection of strains indicated
      that biofilm-forming isolates entered epithelial cells with significantly lower
      efficiency than biofilm-negative strains. We suggest that prtF1-negative
      macrolide-susceptible or mef(A)-carrying isolates, which are poorly equipped to
      enter cells, may use biofilm to escape antimicrobial treatments and survive
      within the host. In this view, biofilm formation by S. pyogenes could be
      responsible for unexplained treatment failures and recurrences due to susceptible
      microorganisms.

PMID- 16891484
TI  - New Staphylococcus aureus genotyping method based on exotoxin (set) genes.
AB  - A variety of methods for genotyping Staphylococcus aureus isolates exists: the
      two most widely used methods are pulsed-field gel electrophoresis (PFGE) and
      multilocus sequence typing (MLST). Here, we describe a sequence-based genotyping
      method based on genes encoding S. aureus superantigen-like proteins, which belong
      to a family of exotoxins called staphylococcal exotoxins. The sequences of PCR
      amplified internal fragments of three different set genes (set2, set5, and set7)
      of 61 well-characterized clinical methicillin-resistant S. aureus (MRSA) and
      methicillin-susceptible S. aureus (MSSA) isolates and reference strains were
      compared. Phylogenetic analysis was performed based on single-nucleotide
      polymorphisms (SNP). The SNP dendrograms of the set gene sequences differentiated
      the 61 isolates into 22 distinct subgroups, designated exotoxin sequence types
      (ETST), while the standard seven-gene MLST profiles differentiated the same 61
      isolates into 19 subgroups. Of the 19 different MLST subgroups, 16 corresponded
      to 16 distinct ETST groups. However, three MLST subgroups, ST1, ST30, and ST36,
      were each further separated into more than one ETST subgroup. The exotoxin-based
      genotyping method was able to discriminate MRSA and MSSA isolates according to
      their specific epidemiological characteristics. This SNP analysis of the three
      set genes is thus equally or more discriminatory than the seven-gene MLST method,
      providing a good alternative typing tool for a laboratory that has sequencing
      capability.

PMID- 16891485
TI  - Measles virus-specific antibody levels in individuals in Argentina who received a
      one-dose vaccine.
AB  - In spite of active measles virus (MV) vaccination strategies, reemergence
      continues to occur, impairing global eradication programs. The immune status
      against measles was evaluated in 350 vaccinated healthy Argentine children and
      teenagers who received a single dose of the MV Schwarz strain Lirugen vaccine
      (Aventis Pasteur). Sera were assessed for immunoglobulin G (IgG) antibodies by a
      commercial enzyme immunoassay (EIA) (Enzygnost; Behring), an in-house EIA, and
      neutralization EIA. Results obtained with these methods showed a marked decline
      in IgG level with increasing age. At 1 to 4 years of age, 84% of children had IgG
      antibodies above 200 mIU/ml, conventionally accepted as protective levels,
      whereas only 32% of older children and teenagers had antibody levels exceeding
      200 mIU/ml. Moreover, the MV IgG content in the teenage group was significantly
      lower than the IgG antibody level of the group of younger children (P < 0.0001).
      In contrast, screening for IgG antibody levels to inactivated tetanus vaccine
      showed that, on average, 80% of this population was fully protected and that this
      high level of protection remained through the teenage years. This study suggests
      that within this population a considerable proportion of individuals had low
      measles antibody levels that may be insufficient to protect against reinfections
      or clinical disease.

PMID- 16891486
TI  - Role of metapneumovirus in viral respiratory infections in young children.
AB  - The contribution of human metapneumovirus (hMPV) relative to that of other
      respiratory viruses as a cause of respiratory infections in children less than 1
      year old has been evaluated. From October 2003 to April 2004, nasopharyngeal
      samples from 211 children less than 1 year old were analyzed to detect
      respiratory viruses. Respiratory syncytial virus (RSV) was the predominant virus
      isolated (96 children [45.5%]), followed by influenza A virus, parainfluenza
      virus, adenovirus, cytomegalovirus, and herpes simplex virus type 1, which were
      only occasionally detected. From January 2004 to April 2004, a nested
      retrotranscription-PCR, using in-house primers directed to the matrix protein
      gene of hMPV, was carried out on samples in which no other viruses were detected.
      hMPV was detected in 18 (16.2%) children, indicating that this virus was the
      second-most-frequent cause of viral respiratory infections in children less than
      1 year old. The rate of hospitalization for RSV- and hMPV-infected children was
      higher than 75%. While RSV had a peak from December to February, hMPV was
      increasingly detected from January to April. The mean age of hMPV-infected
      children (6.44 +/- 3.64 [mean +/- standard deviation] months) was significantly
      higher than that of RSV-infected children (3.99 +/- 2.96 [mean +/- standard
      deviation] months). On the other hand, 64.3% of the RSV-infected children and
      12.5% of the hMPV-infected children showed high levels of C-reactive protein.
      Although several authors have reported that clinical symptoms of hMPV-positive
      patients mirrored those of RSV-positive patients, differences between the two
      viruses can be found.

PMID- 16891487
TI  - Invasive meningococcal disease in Quebec, Canada, due to an emerging clone of ST
      269 serogroup B meningococci with serotype antigen 17 and serosubtype antigen
      P1.19 (B:17:P1.19).
AB  - During periods of endemic meningococcal disease, serogroup B Neisseria
      meningitidis is responsible for a significant percentage of invasive diseases,
      and no particular clone or strain predominates (F. E. Ashton and D. A. Caugant,
      Can. J. Microbiol. 47: 293-289, 2001), However, in the winter of 2004 to 2005, a
      cluster of serogroup B meningococcal disease occurred in one region in the
      province of Quebec, Canada. The N. meningitidis strain responsible for this
      cluster of cases was identified as sequence type ST-269 with the antigenic
      formula B:17:P1.19. Retrospective analysis of isolates from 2000 onwards showed
      that this clone first emerged in the province of Quebec in 2003. The emergence of
      this clone of serogroup B meningococci occurred after a mass vaccination against
      serogroup C N. meningitidis, suggesting possible capsule replacement.

PMID- 16891488
TI  - Real-time quantitative broad-range PCR assay for detection of the 16S rRNA gene
      followed by sequencing for species identification.
AB  - Here we determined the analytical sensitivities of broad-range real-time PCR
      based assays employing one of three different genomic DNA extraction protocols in
      combination with one of three different primer pairs targeting the 16S rRNA gene
      to detect a panel of 22 bacterial species. DNA extraction protocol III, using
      lysozyme, lysostaphin, and proteinase K, followed by PCR with the primer pair
      Bak11W/Bak2, giving amplicons of 796 bp in length, showed the best overall
      sensitivity, detecting DNA of 82% of the strains investigated at concentrations
      of < or =10(2) CFU in water per reaction. DNA extraction protocols I and II,
      using less enzyme treatment, combined with other primer pairs giving shorter
      amplicons of 466 bp and 342 or 346 bp, respectively, were slightly more sensitive
      for the detection of gram-negative but less sensitive for the detection of gram
      positive bacteria. The obstacle of detecting background DNA in blood samples
      spiked with bacteria was circumvented by introducing a broad-range hybridization
      probe, and this preserved the minimal detection limits observed in samples devoid
      of blood. Finally, sequencing of the amplicons generated using the primer pair
      Bak11W/Bak2 allowed species identification of the detected bacterial DNA. Thus,
      broad-spectrum PCR targeting the 16S rRNA gene in the quantitative real-time
      format can achieve an analytical sensitivity of 1 to 10 CFU per reaction in
      water, avoid detection of background DNA with the introduction of a broad-range
      probe, and generate amplicons that allow species identification of the detected
      bacterial DNA by sequencing. These prerequisites are important for its
      application to blood-containing patient samples.

PMID- 16891489
TI  - Analysis of secA1 gene sequences for identification of Nocardia species.
AB  - Molecular methodologies, especially 16S rRNA gene sequence analysis, have allowed
      the recognition of many new species of Nocardia and to date have been the most
      precise methods for identifying isolates reliably to the species level. We
      describe here a novel method for identifying Nocardia isolates by using sequence
      analysis of a portion of the secA1 gene. A region of the secA1 gene of 30 type or
      reference strains of Nocardia species was amplified using secA1-specific primers.
      Sequence analysis of 468 bp allowed clear differentiation of all species, with a
      range of interspecies similarity of 85.0% to 98.7%. Corresponding 16S rRNA gene
      sequences of a 1,285-bp region for the same isolates showed a range of
      interspecies similarity of 94.4 to 99.8%. In addition to the type and reference
      strains, a 468-bp fragment of the secA1 gene was sequenced from 40 clinical
      isolates of 12 Nocardia species previously identified by 16S rRNA gene sequence
      analysis. The secA1 gene sequences of most isolates showed >99.0% similarity to
      the secA1 sequences of the type or reference strain to which their identification
      corresponded, with a range of 95.3 to 100%. Comparison of the deduced 156 amino
      acid sequences of the SecA1 proteins of the clinical isolates showed between zero
      and two amino acid residue differences compared to that of the corresponding type
      or reference strain. Sequencing of the secA1 gene, and using deduced amino acid
      sequences of the SecA1 protein, may provide a more discriminative and precise
      method for the identification of Nocardia isolates than 16S rRNA gene sequencing.

PMID- 16891491
TI  - Effect of sequence variation in Plasmodium falciparum histidine- rich protein 2
      on binding of specific monoclonal antibodies: Implications for rapid diagnostic
      tests for malaria.
AB  - The ability to accurately diagnose malaria infections, particularly in settings
      where laboratory facilities are not well developed, is of key importance in the
      control of this disease. Rapid diagnostic tests (RDTs) offer great potential to
      address this need. Reports of significant variation in the field performance of
      RDTs based on the detection of Plasmodium falciparum histidine-rich protein 2
      (HRP2) (PfHRP2) and of significant sequence polymorphism in PfHRP2 led us to
      evaluate the binding of four HRP2-specific monoclonal antibodies (MABs) to
      parasite proteins from geographically distinct P. falciparum isolates, define the
      epitopes recognized by these MABs, and relate the copy number of the epitopes to
      MAB reactivity. We observed a significant difference in the reactivity of the
      same MAB to different isolates and between different MABs tested with single
      isolates. When the target epitopes of three of the MABs were determined and
      mapped onto the peptide sequences of the field isolates, significant variability
      in the frequency of these epitopes was observed. These findings support the role
      of sequence variation as an explanation for variations in the performance of HRP2
      based RDTs and point toward possible approaches to improve their diagnostic
      sensitivities.

PMID- 16891490
TI  - Clonality and antimicrobial resistance gene profiles of multidrug- resistant
      Salmonella enterica serovar infantis isolates from four public hospitals in Rio
      de Janeiro, Brazil.
AB  - In Brazil, Salmonella enterica serovar Infantis resistant to various
      antimicrobials, including cephalosporins, has been identified as an etiological
      agent of severe gastroenteritis in hospitalized children since 1994. In this
      study, 35 serovar Infantis strains, isolated from children admitted to four
      different Rio de Janeiro, Brazil, hospitals between 1996 and 2001, were
      characterized by pulsed-field gel electrophoresis (PFGE) and antimicrobial
      susceptibility testing in order to determine their genetic relatedness and
      antimicrobial resistance profiles. Thirty-four serovar Infantis strains were
      resistant to at least two antibiotic classes, and all 35 strains were susceptible
      to fluoroquinolones, cephamycin, and carbapenem. Extended-spectrum beta-lactamase
      (ESBL) screening by double-disk diffusion indicated that 32 serovar Infantis
      strains (91.4%) produced beta-lactamases that were inhibited by clavulanic acid.
      Antimicrobial resistance gene profiles were determined by PCR for a subset of 11
      multidrug-resistant serovar Infantis strains, and putative ESBLs were detected by
      isoelectric focusing. Ten serovar Infantis strains carried bla(TEM), catI,
      ant(3")Ia and/or ant(3")Ib, sulI and/or sulII, and tet(D) genes as well as an
      integron-associated aac(6')-Iq cassette. Eight strains possessed at least four
      different beta-lactamases with pI profiles that confirmed the presence of both
      ESBLs and non-ESBLs. Our PFGE profiles indicated that 33 serovar Infantis strains
      isolated from Rio de Janeiro hospitals came from the same genetic lineage.

PMID- 16891492
TI  - Multitypic hepatitis C virus infection identified by real-time nucleotide
      sequencing of minority genotypes.
AB  - The prevalence of concurrent multitypic hepatitis C virus (HCV) infection is
      uncertain. A sensitive and specific approach to identifying minority HCV
      genotypes in blood is presented. Following serum extraction and reverse
      transcription PCR to amplify cDNA originating from the viral 5' noncoding region,
      the amplified product mixture was treated with genotype-specific restriction
      endonuclease to digest the dominant genotype. Residual amplicons were subjected
      to PCR cloning and then to real-time DNA sequencing using a Pyrosequencer to
      identify the remaining genotypes. Dilution experiments showed that minority
      genotypes may be detected when they represent 1:10,000 of the total population
      and in serum specimens with viral loads as low as 1,000 IU/ml. Of 37 patients
      with bleeding disorders and 44 injecting drug users, infection by more than one
      HCV genotype was found in 7 (19%) and 4 (9%) patients, respectively. The low rate
      of detection in people at high risk of repeated HCV infection suggests that
      multitypic HCV carriage is uncommon.

PMID- 16891493
TI  - Comparative analysis of prevalence, risk factors, and molecular epidemiology of
      antibiotic-associated diarrhea due to Clostridium difficile, Clostridium
      perfringens, and Staphylococcus aureus.
AB  - We prospectively studied the comparative epidemiology and risk factors for
      Clostridium difficile, Clostridium perfringens, and Staphylococcus aureus
      antibiotic-associated diarrhea (AAD). Four thousand six hundred fifty-nine
      inpatient fecal specimens (11 months) were tested for C. difficile cytotoxin, C.
      perfringens enterotoxin, and S. aureus by Vero cell assay, enzyme-linked
      immunosorbent assay, and growth on fresh blood agar, respectively. Two distinct
      age-, sex-, and location-matched control patient groups were used for
      multivariate logistic regression risk factor analyses: symptomatic patients who
      were AAD pathogen negative and asymptomatic patients with histories of recent
      antimicrobial therapy. All AAD pathogen isolates were DNA fingerprinted. In AAD
      cases, the prevalences of C. difficile cytotoxin, C. perfringens enterotoxin, and
      S. aureus were 12.7%, 3.3%, and 0.2%, respectively (15.8% overall). Age of >70
      years was a common risk factor. Other risk factors for infective AAD and C.
      difficile AAD included length of hospital stay and use of feeding tubes (length
      of stay odds ratios [OR], 1.017 and 1.012; feeding tube OR, 1.864 and 2.808).
      Female gender and use of antacids were significantly associated with increased
      risk of C. perfringens AAD (OR, 2.08 and 2.789, respectively), but unlike what
      was found for C. difficile AAD, specific antibiotic classes were not associated
      with increased risk. A limited number of genotypes caused the majority of C.
      difficile and C. perfringens AAD cases. Similar to what was found for C.
      difficile AAD, there was epidemiological evidence of C. perfringens AAD case
      clustering and reinfection due to different strains. C. difficile AAD was
      approximately 4 and 60 times more common than C. perfringens AAD and S. aureus
      AAD, respectively. Risk factors for these AAD pathogens differed, highlighting
      the need to define specific control measures. There is evidence of nosocomial
      transmission in cases of C. perfringens AAD.

PMID- 16891494
TI  - European multicenter evaluation of high-density DNA probe arrays for detection of
      hepatitis B virus resistance mutations and identification of genotypes.
AB  - Polymorphisms along the hepatitis B virus (HBV) genome have an impact on disease
      outcome, sensitivity to antiviral treatment, escape from vaccination, and
      laboratory diagnosis. We have designed a diagnostic tool based on duplex
      amplification of the whole HBV genome and a high-density DNA chip designed to
      detect 245 mutations, 20 deletions, and 2 insertions at 151 positions and to
      determine the genotype of the virus in serum. Assay performances were evaluated
      with 170 samples, characterized by determination of viral load and sequencing of
      the Pol, S, and precore genes and the basal core promoter. One hundred fifty
      three samples (90%) could be amplified and analyzed by the chip. Only two samples
      with more than 10(3) genome copies/ml could not be analyzed. Genotype had no
      impact on analytical sensitivity. Reproducibility studies showed no difference
      between repeats for codon and genotype determination. Genotype determination by
      sequencing and the chip were concordant in 148 of 151 samples. Twelve thousand
      one hundred sixty-one codons were analyzed by both techniques. Only 89.4% could
      be determined by sequencing, and among the remaining 11,335 codons, 92.8% were
      identical by sequencing and the chip. Failures to identify an amino acid by the
      chip were mainly due to reduced hybridization efficiency attributed to unexpected
      polymorphisms. Optimization of the chip-based reagent for the analysis of the HBV
      genome is ongoing. This first evaluation showed that DNA chip technology can
      provide important information in relation to the clinical management of chronic
      hepatitis B.

PMID- 16891495
TI  - Prevalence of antibodies against herpes simplex virus types 1 and 2 in children
      and young people in an urban region in Tanzania.
AB  - Herpes simplex virus type 1 (HSV-1) is transmitted by close contact, both sexual
      and nonsexual, and infections are acquired during childhood and adolescence.
      Herpes simplex virus type 2 (HSV-2), however, is thought to be transmitted mainly
      by sexual contact. Most HSV-2 infections are consequently expected to occur after
      the onset of sexual activity. Recent reports indicate an increasing prevalence of
      HSV-2 on the African continent, but most studies have been performed on adult
      cohorts. In the present study, we collected sera from Tanzanian children and
      young persons from 1 to 20 years old, with at least 100 individuals in each age
      group. Antibodies against HSV-1 and HSV-2 were detected by an in-house Western
      blot method which was shown to perform well in comparison with a commercial
      Western blot assay. Type-specific antibodies were also analyzed by two
      noncommercial enzyme-linked immunosorbent assay methods based upon the
      antigenicities of branched synthetic oligopeptides corresponding to epitopes in
      glycoprotein G of HSV-1 or HSV-2. The prevalence of HSV-1 antibodies increased
      gradually from 73% for the age group of 1 to 4 years to 92% for the age group of
      17 to 20 years. The prevalence of HSV-2 antibodies was unexpectedly high, as 15%
      of the children were infected by the age of 8 years, with the incidence
      increasing gradually to 40% in the age group of 17 to 20 years. The reason for
      this unexpectedly high frequency is not clear but could suggest that nonsexual
      transmission of HSV-2 is more common than previously thought. There was no
      statistically significant association between seropositivities for HSV-2 and
      human immunodeficiency virus.

PMID- 16891496
TI  - Typing of human adenoviruses in specimens from immunosuppressed patients by PCR
      fragment length analysis and real-time quantitative PCR.
AB  - Currently, 51 human adenovirus (AdV) serotypes, which are divided into six
      species (A to F), are known. AdV infections are a major cause of morbidity and
      mortality in immunosuppressed individuals, particularly in allogeneic stem cell
      transplant (SCT) recipients. Any AdV species may cause life-threatening disease,
      but little information is available on the clinical relevance of individual
      serotypes. The use of serological testing for serotype identification is limited
      due to the impaired immune response during the posttransplant period. A new
      molecular approach to serotype identification is presented here that exploits
      variable regions within the hexon gene. All serotypes belonging to the species A,
      B, C, E, and F can be determined by fragment length analysis of a single PCR
      product. For species C, which is the most prevalent in many geographic regions,
      an alternative technique based on serotype-specific real-time quantitative PCR
      was established. Of 135 consecutive pediatric patients screened for AdV
      infections after allogeneic SCT, 40 tested positive. Detailed analysis revealed
      the presence of 10 different serotypes; serotypes 1 and 2 from species C (C01 and
      C02) showed the highest prevalence, accounting for 77% of the AdV-positive cases.
      Representatives of other species were observed less commonly: serotype A12 in
      6.5%; serotype A31 in 4.5%; and B03, B16, C05, C06, D19, and F41 in 2%. The
      approach to rapid molecular serotype analysis presented here provides a basis for
      detailed studies on adenovirus epidemiology and on the transmission of nosocomial
      infections. Moreover, in view of the increasing importance of tailored therapy
      approaches, serotype identification may in the future have implications for the
      selection of the most appropriate antiviral treatment.

PMID- 16891497
TI  - Epidemiology of candidemia in Brazil: a nationwide sentinel surveillance of
      candidemia in eleven medical centers.
AB  - Candidemia studies have documented geographic differences in rates and
      epidemiology, underscoring the need for surveillance to monitor trends. We
      conducted prospective candidemia surveillance in Brazil to assess the incidence,
      species distribution, frequency of antifungal resistance, and risk factors for
      fluconazole-resistant Candida species. Prospective laboratory-based surveillance
      was conducted from March 2003 to December 2004 in 11 medical centers located in 9
      major Brazilian cities. A case of candidemia was defined as the isolation of
      Candida spp. from a blood culture. Incidence rates were calculated per 1,000
      admissions and 1,000 patient-days. Antifungal susceptibility tests were performed
      by using the broth microdilution assay, according to the Clinical and Laboratory
      Standards Institute guidelines. We detected 712 cases, for an overall incidence
      of 2.49 cases per 1,000 admissions and 0.37 cases per 1,000 patient-days. The 30
      day crude mortality was 54%. C. albicans was the most common species (40.9%),
      followed by C. tropicalis (20.9%) and C. parapsilosis (20.5%). Overall, decreased
      susceptibility to fluconazole occurred in 33 (5%) of incident isolates, 6 (1%) of
      which were resistant. There was a linear correlation between fluconazole and
      voriconazole MICs (r = 0.54 and P < 0.001 [Spearman's rho]). This is the largest
      multicenter candidemia study conducted in Latin America and shows the substantial
      morbidity and mortality of candidemia in Brazil. Antifungal resistance was rare,
      but correlation between fluconazole and voriconazole MICs suggests cross
      resistance may occur.

PMID- 16891498
TI  - Comparative study using various methods for identification of Staphylococcus
      species in clinical specimens.
AB  - Coagulase-negative staphylococci (CNS) play a predominant role in nosocomial
      infections. Rapid, reliable identification of these organisms is essential for
      accurate diagnosis and prompt effective treatment of these infections. Quite
      recently, the VITEK 2 g-positive (gram-positive [GP]) identification card
      (bioMerieux) has been redesigned for greater accuracy in the identification of
      gram-positive cocci. We compared the BD Phoenix (Becton Dickinson) and VITEK 2
      (bioMerieux) automated microbiology systems, using their respective update
      version cards, and the API ID32 STAPH test. The glyceraldehyde-3-phosphate
      dehydrogenase (gap) gene-based T-RFLP (terminal restriction fragment length
      polymorphism) method was used for verifying the results. In total, 86 clinical
      isolates of CNS and 27 reference strains were analyzed. The results show that for
      identification of CNS, the automated identification methods using the newest
      VITEK 2 and BD Phoenix identification cards are comparable. However, API ID32
      STAPH revealed more correct results compared to both automated microbiology
      systems. Despite the increased performance of the phenotypic automated
      identification systems compared to the former versions, molecular methods, e.g.,
      the gap-based T-RFLP method, still show superior accuracy in identifying
      Staphylococcus species other than Staphylococcus aureus.

PMID- 16891499
TI  - Characterization of a large outbreak by CTX-M-1-producing Klebsiella pneumoniae
      and mechanisms leading to in vivo carbapenem resistance development.
AB  - All extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae isolates
      from patients admitted to and adult intensive care unit were prospectively
      documented from 2002 to 2005, when a large outbreak (51 patients affected) of
      multiresistant ESBL-producing Klebsiella pneumoniae infection was detected. The
      involvement of a single K. pneumoniae clone was demonstrated by pulsed-field gel
      electrophoresis. In addition to the ESBL-mediated resistance, the epidemic strain
      uniformly showed cross-resistance to ciprofloxacin, gentamicin, tobramycin,
      trimethoprim-sulfamethoxazole, and tetracycline, whereas resistance to the beta
      lactam-beta-lactamase inhibitor combinations was variable. The ESBL involved was
      CTX-M-1, as demonstrated by isoelectric focusing, PCR amplification, and
      sequencing. CTX-M-1 as well as the aminoglycoside resistance determinants were
      encoded in a 50-kb plasmid that could be transferred to Escherichia coli only by
      transformation. In two of the infected patients, carbapenem resistance
      development (MICs of 8 to 12, 16, and >32 microg/ml for imipenem, meropenem, and
      ertapenem, respectively) was documented, both in clinical samples and in
      intestinal colonization studies. The analysis of the outer membrane proteins of
      the carbapenem-susceptible and -resistant isolates revealed that the former
      expressed only one of the two major porins, OmpK36, whereas the latter did not
      express either of them. In one of the cases, the lack of expression of OmpK36 was
      demonstrated to be mediated by the interruption of the coding sequence by the
      insertion sequence IS26. This is the first report of a large outbreak of CTX-M-1
      producing Enterobacteriaceae and, curiously, the first documented description in
      the literature of CTX-M-1 in K. pneumoniae, despite the fact that this enzyme has
      been found in multiple species. Furthermore, we document and characterize for the
      first time carbapenem resistance development in CTX-M-1-producing
      Enterobacteriaceae.

PMID- 16891500
TI  - Genetic diversity of PspA types among nasopharyngeal isolates collected during an
      ongoing surveillance study of children in Brazil.
AB  - Pneumococcal surface protein A (PspA) has been considered a potential candidate
      for human vaccines because of its serotype-independent protective immunity.
      Nasopharyngeal (NP) pneumococcal colonization is highly prevalent in infants and
      precedes the invasive disease. Thus, prevention of NP colonization may reduce the
      burden of pneumococcal disease in children. Scarce information focusing on PspA
      from pneumococcal carriage in humans is available. We examined the genetic
      diversity of PspA from NP isolates obtained during an ongoing pneumococcal
      surveillance study with children. PspA families and clades of 183 community
      acquired Streptococcus pneumoniae NP isolates from healthy children (n = 97) and
      children with respiratory tract infections (n = 48), pneumonia (n = 33), or
      meningitis (n = 5) were investigated. Overall, 79.8% (n = 146) of the
      pneumococcal isolates were classified as PspA family 1 (35.5%) and family 2
      (44.3%), whereas 20.2% of the isolates could not be typed. The distribution of
      PspA families and clades did not differ significantly according to the clinical
      status of the children. A dendrogram comparing the genetic relationship between
      the amino acid sequences of the clade-defining region of PspA from NP strains
      together with 24 invasive reference strains (GenBank) closely reproduced the
      profile of the families and clades previously reported for pneumococcal invasive
      strains. These findings strengthen the idea that the use of PspA as a vaccine
      antigen may protect children against carriage as well as invasive pneumococcal
      disease.

PMID- 16891501
TI  - Sensitivity analysis and potential uses of a novel gamma interferon release assay
      for diagnosis of tuberculosis.
AB  - Sputum smears for acid-fast bacilli (AFB) are the primary methods for diagnosis
      of tuberculosis (TB) in many countries. The tuberculin skin test (TST) is the
      primary method for diagnosis of latent TB infection (LTBI) worldwide. The poor
      sensitivity of the former and the poor specificity of the latter warrant the
      development of new tests and strategies to enhance diagnostic capabilities. We
      evaluated the sensitivity of an "in-tube" gamma interferon release assay (IGRA)
      using TB-specific antigens in comparison to the TST and the sputum smear for AFB
      in TB cases in South Africa. The sensitivity of the IGRA for TB was considered a
      surrogate of sensitivity in LTBI. Among 154 patients with a positive culture for
      Mycobacterium tuberculosis, the sensitivity of the IGRA for the diagnosis of TB
      varied by clinical subgroup from 64% to 82%, that of the TST varied from 85% to
      94%, and that of two sputum smears for AFB varied from 35% to 53%. The
      sensitivity of the IGRA in human immunodeficiency virus (HIV)-infected TB cases
      was 81%. HIV-infected TB patients were significantly more likely to have
      indeterminate IGRA results and produced quantitatively less gamma interferon in
      response to TB-specific antigens than HIV-negative TB patients. The overall
      sensitivity of the TST in all TB cases was higher than that of the IGRA (90%
      versus 76%, respectively). The combined sensitivities of the TST plus IGRA and
      TST plus a single sputum smear were 96% and 93%, respectively. The TST combined
      with IGRA or with a single sputum smear may have a role in excluding the
      diagnosis of TB in some settings.

PMID- 16891502
TI  - Rapid detection of the Mycobacterium tuberculosis Beijing genotype and its
      ancient and modern sublineages by IS6110-based inverse PCR.
AB  - The Mycobacterium tuberculosis Beijing genotype strains appear to be
      hypervirulent and associated with multidrug-resistant tuberculosis. Therefore,
      the development of a both rapid and simple method to detect the M. tuberculosis
      Beijing genotype is of clinical interest per se. Previously, we described a
      simple and fast approach to detect the Beijing genotype based on IS6110 inverse
      PCR typing. Here, we evaluated this method against a large, diverse, and recent
      collection of strains. The study sample included 866 M. tuberculosis strains
      representing but not limited to the regions in Russia, Europe, and East Asia
      where the Beijing genotype is endemic. Based on a spoligotyping method, 408
      strains were identified as Beijing genotypes; they were additionally subdivided
      into ancient and modern sublineages based on the analysis of the NTF locus. All
      strains were further subjected to the IS6110-based inverse PCR. All of the
      Beijing genotype strains were found to have identical two-band (ancient
      sublineage) or three-band (modern sublineage) profiles that were easily
      recognizable and distinct from the profiles of the non-Beijing strains.
      Therefore, we suggest using IS6110-based inverse-PCR typing for the correct
      identification of the Beijing genotype and its major sublineages. The method is
      fast and inexpensive and does not require additional experiments but instead is
      implemented in the routine typing method of M. tuberculosis.

PMID- 16891503
TI  - Robust sequence selection method used to develop the FluChip diagnostic
      microarray for influenza virus.
AB  - DNA microarrays have proven to be powerful tools for gene expression analyses and
      are becoming increasingly attractive for diagnostic applications, e.g., for virus
      identification and subtyping. The selection of appropriate sequences for use on a
      microarray poses a challenge, particularly for highly mutable organisms such as
      influenza viruses, human immunodeficiency viruses, and hepatitis C viruses. The
      goal of this work was to develop an efficient method for mining large databases
      in order to identify regions of conservation in the influenza virus genome. From
      these regions of conservation, capture and label sequences capable of
      discriminating between different viral types and subtypes were selected. The
      salient features of the method were the use of phylogenetic trees for data
      reduction and the selection of a relatively small number of capture and label
      sequences capable of identifying a broad spectrum of influenza viruses. A
      detailed experimental evaluation of the selected sequences is described in a
      companion paper. The software is freely available under the General Public
      License at http://www.colorado.edu/chemistry/RGHP/software/.

PMID- 16891504
TI  - Experimental evaluation of the FluChip diagnostic microarray for influenza virus
      surveillance.
AB  - Global surveillance of influenza is critical for improvements in disease
      management and is especially important for early detection, rapid intervention,
      and a possible reduction of the impact of an influenza pandemic. Enhanced
      surveillance requires rapid, robust, and inexpensive analytical techniques
      capable of providing a detailed analysis of influenza virus strains. Low-density
      oligonucleotide microarrays with highly multiplexed "signatures" for influenza
      viruses offer many of the desired characteristics. However, the high mutability
      of the influenza virus represents a design challenge. In order for an influenza
      virus microarray to be of utility, it must provide information for a wide range
      of viral strains and lineages. The design and characterization of an influenza
      microarray, the FluChip-55 microarray, for the relatively rapid identification of
      influenza A virus subtypes H1N1, H3N2, and H5N1 are described here. In this work,
      a small set of sequences was carefully selected to exhibit broad coverage for the
      influenza A and B viruses currently circulating in the human population as well
      as the avian A/H5N1 virus that has become enzootic in poultry in Southeast Asia
      and that has recently spread to Europe. A complete assay involving extraction and
      amplification of the viral RNA was developed and tested. In a blind study of 72
      influenza virus isolates, RNA from a wide range of influenza A and B viruses was
      amplified, hybridized, labeled with a fluorophore, and imaged. The entire
      analysis time was less than 12 h. The combined results for two assays provided
      the absolutely correct types and subtypes for an average of 72% of the isolates,
      the correct type and partially correct subtype information for 13% of the
      isolates, the correct type only for 10% of the isolates, false-negative signals
      for 4% of the isolates, and false-positive signals for 1% of the isolates. In the
      overwhelming majority of cases in which incomplete subtyping was observed, the
      failure was due to the nucleic acid amplification step rather than limitations in
      the microarray.

PMID- 16891505
TI  - Serotype 1-specific monoclonal antibody-based antigen capture immunoassay for
      detection of circulating nonstructural protein NS1: Implications for early
      diagnosis and serotyping of dengue virus infections.
AB  - Rapid diagnosis and serotyping of dengue virus (DV) infections are important for
      timely clinical management and epidemiological control in areas where multiple
      flaviviruses are endemic. However, the speed and accuracy of diagnosis must be
      balanced against test cost and availability, especially in developing countries.
      We developed a specific antigen capture enzyme-linked immunosorbent assay (ELISA)
      for early detection and serotyping of DV serotype 1 (DV1) by using well
      characterized monoclonal antibodies (MAbs) specific to nonstructural protein 1
      (NS1) of DV1. With this assay, a total of 462 serum specimens from clinically
      probable DV1-infected patients during the DV1 epidemic in Guangdong, China, in
      2002 and 2003 were analyzed. DV1 NS1 was detectable in blood circulation from the
      first day up to day 18 after onset of symptoms, with a peak at days 6 to 10. The
      sensitivity of DV1 NS1 detection in serum specimens with reference to results
      from reverse transcriptase PCR was 82%, and the specificity was 98.9% with
      reference to 469 healthy blood donors. No cross-reactions with any of the other
      three DV serotypes or other closely related members of the genus Flavivirus
      (Japanese encephalitis virus and Yellow fever virus) were observed when tested
      with the clinical specimens or virus cultures. These findings suggest that the
      serotype-specific MAb-based NS1 antigen capture ELISA may be a valuable tool for
      early diagnosis and serotyping of DV infections, while also providing a
      standardized assay for the analysis of a great number of clinical samples with
      convenience and cost-effectiveness.

PMID- 16891506
TI  - Characterization of Shigella strains in Iran by plasmid profile analysis and PCR
      amplification of ipa genes.
AB  - To characterize Shigella clinical strains, we studied 82 Shigella strains
      recovered from 719 stool samples of patients with bloody diarrhea in Shiraz,
      Iran, over the period from April to October 2003. Serological assay classified
      the Shigella isolates as follows: 61 (74.39%) Shigella sonnei isolates, 16
      (19.51%) Shigella flexneri isolates, 3 (3.65%) Shigella boydii isolates, and 2
      (2.43%) Shigella dysenteriae isolates. In an antibiogram test, all Shigella
      strains were susceptible to ceftazidime, ciprofloxacin, and ceftriaxone. They
      showed high degrees of sensitivity to nalidixic acid, gentamicin, cephalothin,
      and amikacin. Approximately 90.24% of the Shigella isolates were resistant to co
      trimoxazole. The plasmid profile patterns of all strains were determined by a
      modified alkaline lysis method. The average number of plasmid bands for each
      strain was 9.5. By plasmid profile analysis we identified 56 genotypes among all
      isolates and 42, 14, 3, and 2 genotypes among the S. sonnei, S. flexneri, S.
      boydii, and S. dysenteriae strains, respectively. PCR assays showed that all
      isolates were positive for two virulence genes, ipaBCD and ipaH. In conclusion,
      these data mandate local monitoring of drug resistance and its consideration in
      the empirical therapy of Shigella infections. These results also demonstrate that
      plasmid profile analysis is more reliable than antibiotic susceptibility pattern
      analysis for the identification of Shigella epidemic strains isolated in Iran.

PMID- 16891507
TI  - Molecular dipstick test for diagnosis of sleeping sickness.
AB  - Human African trypanosomiasis (HAT) or sleeping sickness is a neglected disease
      that affects poor rural populations across sub-Saharan Africa. Confirmation of
      diagnosis is based on detection of parasites in either blood or lymph by
      microscopy. Here we present the development and the first-phase evaluation of a
      simple and rapid test (HAT-PCR-OC [human African trypanosomiasis-PCR
      oligochromatography]) for detection of amplified Trypanosoma brucei DNA. PCR
      products are visualized on a dipstick through hybridization with a gold
      conjugated probe (oligochromatography). Visualization is straightforward and
      takes only 5 min. Controls both for the PCR and for DNA migration are
      incorporated into the assay. The lower detection limit of the test is 5 fg of
      pure T. brucei DNA. One parasite in 180 microl of blood is still detectable.
      Sensitivity and specificity for T. brucei were calculated at 100% when tested on
      blood samples from 26 confirmed sleeping sickness patients, 18 negative controls
      (nonendemic region), and 50 negative control blood samples from an endemic
      region. HAT-PCR-OC is a promising new tool for diagnosis of sleeping sickness in
      laboratory settings, and the diagnostic format described here may have wider
      application for other infectious diseases.

PMID- 16891508
TI  - Strain-specific differences in two large Mycobacterium tuberculosis genotype
      clusters in isolates collected from homeless patients in New York City from 2001
      to 2004.
AB  - We studied two large Mycobacterium tuberculosis genotype clusters associated with
      recent outbreaks in homeless persons to determine factors associated with these
      tuberculosis (TB) strains. Isolates from all culture-positive TB cases diagnosed
      from 1 January 2001 to 31 December 2004 were genotyped. Patients whose isolates
      had identical restriction fragment length polymorphism patterns and spoligotypes
      were considered clustered. Health department records were reviewed and
      reinterviews attempted for clustered cases. Patients with the Cs30 and BEs75
      strains were compared to other genotypically clustered cases and to each other.
      The two largest genotype clusters among homeless persons were the Cs30 strain (n
      = 105) and the BEs75 strain (n = 47). Fifty-one (49%) patients with the Cs30
      strain and 28 (60%) with the BEs75 strain were homeless. Compared to patients
      with the BEs75 strain, patients with the Cs30 strain were less likely to be
      respiratory acid-fast bacillus smear positive (51% versus 72%). Furthermore,
      patients with the BEs75 strain were more likely to be HIV infected (74% versus
      42%), which suggests that most patients with this strain advanced to disease
      after recent infection. Cases in clusters of strains that have been circulating
      in the community over a long time period, such as the Cs30 strain, require
      additional investigation to determine whether clustering is a result of recent
      transmission or reactivation of remote infection.

PMID- 16891510
TI  - Concurrent analysis of nose and groin swab specimens by the IDI-MRSA PCR assay is
      comparable to analysis by individual-specimen PCR and routine culture assays for
      detection of colonization by methicillin-resistant Staphylococcus aureus.
AB  - The IDI-MRSA assay (Infectio Diagnostic, Inc., Sainte-Foy, Quebec, Canada) with
      the Smart Cycler II rapid DNA amplification system (Cepheid, Sunnyvale, CA)
      appears to be sensitive and specific for the rapid detection of nasal
      colonization by methicillin-resistant Staphylococcus aureus (MRSA). We assessed
      the sensitivity and specificity of this assay under conditions in which both the
      nose and cutaneous groin specimens were analyzed together and compared the
      accuracy of this PCR approach to that when these specimens were tested separately
      and by culture assays in an inpatient population with known high rates (12 to
      15%) of MRSA colonization. Of 211 patients screened, 192 had results assessable
      by all three methods (agar-broth culture, separate nose and groin IDI-MRSA assay,
      and combined nose-groin IDI-MRSA assay), with MRSA carriage noted in 31/192
      (16.1%), 41/192 (21.4%), and 36/192 (18.8%) patients by each method,
      respectively. Compared to agar culture results, the sensitivity and specificity
      of the combined nose-groin IDI-MRSA assay were 88.0% and 91.6%, respectively,
      whereas when each specimen was processed separately, the sensitivities were 90.0%
      (nose) and 83.3% (groin) and the specificities were 91.7% (nose) and 90.2%
      (groin). IDI-MRSA assay of a combined nose-groin specimen appears to have an
      accuracy similar to that of the current recommended PCR protocol, providing
      results in a clinically useful time frame, and may represent a more cost
      effective approach to using this assay for screening for MRSA colonization.

PMID- 16891509
TI  - Clonal emergence of extended-spectrum beta-lactamase (CTX-M-2)-producing
      Salmonella enterica serovar Virchow isolates with reduced susceptibilities to
      ciprofloxacin among poultry and humans in Belgium and France (2000 to 2003).
AB  - Antibiotic treatment is not required in cases of Salmonella enterica
      gastroenteritis but is essential in cases of enteric fever or invasive
      salmonellosis or in immunocompromised patients. Although fluoroquinolones and
      extended-spectrum cephalosporins are the drugs of choice to treat invasive
      Salmonella, resistance to these antibiotics is increasing worldwide. During the
      period 2000 to 2003, 90 Salmonella enterica serovar Virchow poultry and poultry
      product isolates and 11 serovar Virchow human isolates were found to produce an
      extended-spectrum beta-lactamase, CTX-M-2, concomitantly with a TEM-1 beta
      lactamase. The bla(CTX-M-2) gene was located on a large conjugative plasmid (>100
      kb). Pulsed-field gel electrophoresis indicated a clonal relationship between the
      poultry and human isolates. All these isolates displayed additional resistance to
      trimethoprim-sulfamethoxazole and tetracycline as well as a reduced
      susceptibility to ciprofloxacin (MICs of between 0.5 and 1 mug/ml). CTX-M-2
      producing Salmonella with a reduced susceptibility to fluoroquinolones
      constitutes a major concern, since such strains could disseminate on a large
      scale and jeopardize classical antibiotic therapy in immunocompromised patients.

PMID- 16891511
TI  - Use of seroconversion panels to estimate delay in detection of anti-human
      immunodeficiency virus antibodies by enzyme-linked immunosorbent assay of pooled
      compared to singleton serum samples.
AB  - The transfusion of unsafe blood worldwide accounts for 5 to 15% of new human
      immunodeficiency virus (HIV) infections, most of which occur in sub-Saharan
      Africa. While developed countries now apply PCR testing of pooled samples, some
      developing countries still do not have universal screening policies. More
      efficient low-cost procedures for the screening of pooled samples have the
      potential to encourage mass screening efforts in resource-poor settings. The aim
      of this study was to estimate the delay in the detection of HIV antibodies in
      pooled serum samples compared to that in singleton serum samples by enzyme-linked
      immunosorbent assay (ELISA) and to evaluate the risk of transfusion-transmitted
      HIV infection during the window period. Serial blood samples obtained from five
      HIV seroconversion panels were mixed with HIV-seronegative blood samples to
      create pools of 6, 12, 16, 24, 32, and 48 samples. The delay in detection of the
      first anti-HIV antibody-positive sample in tests with pooled samples was
      calculated for each pool size and compared to that obtained by testing of
      singleton samples and statistically evaluated by a robust log-linear regression
      analysis. The risk of a false-negative (FN) result caused by dilution was
      estimated by use of the incidence risk/window period model. The additional risk
      of transmission related to ELISA screening of pooled samples for HIV did not
      exceed 9% of the current risk of an FN result (estimated to be 1/1,067,000). The
      countries with virus prevalence rates in donors of less than 15% are expected to
      save up to 30% in the number of tests. ELISA screening of pooled samples could be
      considered in settings where the testing of blood supplies for HIV is not
      routinely done.

PMID- 16891512
TI  - Synergistes group organisms of human origin.
AB  - The bacterial division Synergistes represents a poorly characterized phylotype of
      which only a few isolates have been cultured, primarily from natural
      environments. Recent detection of Synergistes-like sequence types in periodontal
      pockets and caries lesions of humans prompted us to search the R. M. Alden
      culture collection (Santa Monica, Calif.) for biochemically unidentifiable, slow
      growing, obligately anaerobic gram-negative bacilli. Here we report on five
      clinical isolates cultured from peritoneal fluid and two isolates from soft
      tissue infections that together constitute three separate evolutionary lineages
      within the phylogenetic radiation of the division Synergistes. One of these
      clusters was formed by the peritoneal isolates and had an 85% similarity to
      Synergistes jonesii, the first described Synergistes species, which was isolated
      from the rumen of a goat. The isolates from soft-tissue infections, on the other
      hand, formed two distinct lineages moderately related to each other with a
      similarity of approximately 78%. In addition, by using a newly designed 16S rRNA
      gene-based PCR assay with intended target specificity for Synergistes, we found
      that the dominant phylotype from a fecal sample was nearly identical to that of
      the strains obtained from peritonitis. Conversely, sequence types detected in
      periodontal pockets formed a separate cluster that shared a similarity of only
      80% with the soft-tissue isolates. These findings suggest a high diversity of
      medically important Synergistes clades that apparently are unique to individual
      ecological niches in the human body. In conclusion, we now have available the
      first characterized human isolates of the division Synergistes which are
      colonizing, and probably infecting, several sites in the human body.

PMID- 16891513
TI  - Identification of Acinetobacter species and genotyping of Acinetobacter baumannii
      by multilocus PCR and mass spectrometry.
AB  - Members of the genus Acinetobacter are ubiquitous in soil and water and are an
      important cause of nosocomial infections. A rapid method is needed to genotype
      Acinetobacter isolates to determine epidemiology and clonality during infectious
      outbreaks. Multilocus PCR followed by electrospray ionization mass spectrometry
      (PCR/ESI-MS) is a method that uses the amplicon base compositions to genotype
      bacterial species. In order to identify regions of the Acinetobacter genome
      useful for this method, we sequenced regions of six housekeeping genes (trpE,
      adk, efp, mutY, fumC, and ppa) from 267 isolates of Acinetobacter. Isolates were
      collected from infected and colonized soldiers and civilians involved in an
      outbreak in the military health care system associated with the conflict in Iraq,
      from previously characterized outbreaks in European hospitals, and from culture
      collections. Most of the isolates from the Iraqi conflict were Acinetobacter
      baumannii (189 of 216 isolates). Among these, 111 isolates had genotypes
      identical or very similar to those associated with well-characterized A.
      baumannii isolates from European hospitals. Twenty-seven isolates from the
      conflict were found to have genotypes representing different Acinetobacter
      species, including 8 representatives of Acinetobacter genomospecies 13TU and 13
      representatives of Acinetobacter genomospecies 3. Analysis by the PCR/ESI-MS
      method using nine primer pairs targeting the most information-rich regions of the
      trpE, adk, mutY, fumC, and ppa genes distinguished 47 of the 48 A. baumannii
      genotypes identified by sequencing and identified at the species level at least
      18 Acinetobacter species. Results obtained with our genotyping method were
      essentially in agreement with those obtained by pulse-field gel electrophoresis
      analysis. The PCR/ESI-MS genotyping method required 4 h of analysis time to first
      answer with additional samples subsequently analyzed every 10 min. This rapid
      analysis allows tracking of transmission for the implementation of appropriate
      infection control measures on a time scale previously not achievable.

PMID- 16891515
TI  - Evaluation of in situ methods used to detect Mycobacterium avium subsp.
      paratuberculosis in samples from patients with Crohn's disease.
AB  - In common with other diagnostic tests, detection of mycobacteria in tissue by
      microscopic examination is susceptible to spectrum bias. Since Crohn's disease is
      defined by the absence of detectable pathogenic organisms, the use of in situ
      techniques to search for Mycobacterium avium subsp. paratuberculosis in Crohn's
      disease samples requires validation of methods in a paucibacillary setting. To
      generate paucibacillary infection, C57BL/6 mice were artificially infected with
      Mycobacterium avium subsp. paratuberculosis strain K10 and M. tuberculosis H37Rv,
      yielding tissues harboring fewer than one bacillus per oil immersion field.
      Serial sections of organs were then studied by cell wall-based staining
      techniques (Ziehl-Neelsen and auramine rhodamine) and nucleic acid-based staining
      techniques (in situ hybridization [ISH] and indirect in situ PCR [IS PCR]).
      Microscopic examination and measurement of morphometric parameters of bacilli
      revealed that for all methods, Mycobacterium avium subsp. paratuberculosis
      bacilli were observed to be shorter, smaller, and less rod shaped than M.
      tuberculosis bacilli. Ziehl-Neelsen, auramine rhodamine stains, ISH targeting
      rRNA, and IS-PCR targeting the IS900 element afforded comparable sensitivities,
      but for all methods, visualization of individual bacterial forms required
      magnification x1,000. Auramine rhodamine staining and IS-PCR generated positive
      signals in negative controls, indicating the nonspecificity of these assays.
      Together, our results indicate that detection of Mycobacterium avium subsp.
      paratuberculosis bacilli in tissue requires oil immersion microscopy, that rRNA
      ISH provides sensitivity and specificity comparable to those of Ziehl-Neelsen
      staining, and that the microscopic detection limit for Mycobacterium avium subsp.
      paratuberculosis in tissue is governed more by bacterial burden than by staining
      method.

PMID- 16891514
TI  - Molecular analysis of fungal microbiota in samples from healthy human skin and
      psoriatic lesions.
AB  - Psoriasis, a common cutaneous disease of unknown etiology, may be triggered by
      infections, including those due to fungi. Since the fungal community of human
      skin is poorly characterized, we aimed to analyze the mycological microbiota in
      healthy skin and psoriatic lesions. Twenty-five skin samples from five healthy
      subjects (flexor forearm) and three patients with psoriasis were analyzed using
      broad-range 18S ribosomal DNA (rDNA) and 5.8S rDNA/internal transcribed spacer 2
      (ITS2) Malassezia-specific PCR primers. Broad-range PCR analysis indicated that
      most organisms resembled Malassezia. Malassezia-specific 5.8S/ITS2 analysis of
      1,374 clones identified five species and four unknown phylotypes, potentially
      representing new species. The species distribution appears largely host specific
      and conserved in different sites of healthy skin. In three subjects, the
      Malassezia microbiota composition appeared relatively stable over time. Samples
      of Malassezia microbiota from healthy skin and psoriatic lesions were similar in
      one patient but substantially different in two others. These data indicate the
      predominance of Malassezia organisms in healthy human skin, host-specific
      variation, stability over time, and as yet, no consistent patterns
      differentiating psoriatic skin from healthy skin.

PMID- 16891517
TI  - Comparison of the LCx human immunodeficiency virus (HIV) RNA quantitative,
      RealTime HIV, and COBAS AmpliPrep-COBAS TaqMan assays for quantitation of HIV
      type 1 RNA in plasma.
AB  - The LCx human immunodeficiency virus (HIV) RNA Quantitative, RealTime HIV, and
      COBAS AmpliPrep-COBAS TaqMan assays for HIV type 1 (HIV-1) were compared for
      their abilities to quantitate HIV-1 RNA in plasma. High degrees of correlation
      and agreement were observed between the assays. Differences in HIV-1 RNA levels
      according to HIV-1 subtypes did not reach statistical significance.

PMID- 16891516
TI  - Multilocus sequence typing of historical Burkholderia pseudomallei isolates
      collected in Southeast Asia from 1964 to 1967 provides insight into the
      epidemiology of melioidosis.
AB  - A collection of 207 historically relevant Burkholderia pseudomallei isolates was
      analyzed by multilocus sequence typing (MLST). The strain collection contains
      environmental isolates obtained from a geographical distribution survey of B.
      pseudomallei isolates in Thailand (1964 to 1967), as well as stock cultures and
      colony variants from the U.S. Army Medical Research Unit (Malaysia), the Walter
      Reed Army Institute for Research, and the Pasteur Institute (Vietnam). The 207
      isolates of the collection were resolved into 80 sequence types (STs); 56 of
      these were novel. eBURST diagrams predict that the historical-collection STs
      segregate into three complexes when analyzed separately. When added to the 760
      isolates and 365 STs of the B. pseudomallei MLST database, the historical
      collection STs cluster significantly within the main complex of the eBURST
      diagram in an ancestral pattern and alter the B. pseudomallei "population
      snapshot." Differences in colony morphology among reference isolates were found
      not to affect the STs assigned, which were consistent with the original isolates.
      Australian ST84 is likely characteristic of B. pseudomallei isolates of Southeast
      Asia rather than Australia, since multiple environmental isolates from Thailand
      and Malaysia share this ST with the single Australian clinical isolate in the
      MLST database. Phylogenetic evidence is also provided suggesting that Australian
      isolates may not be distinct from those of Thailand, since ST60 is common to
      environmental isolates from both countries. MLST and eBURST are useful tools for
      the study of population biology and epidemiology, since they provide methods to
      elucidate new genetic relationships among bacterial isolates.

PMID- 16891518
TI  - Impact of laboratory cross-contamination on molecular epidemiology studies of
      tuberculosis.
AB  - Laboratory cross-contamination by Mycobacterium tuberculosis is known to be
      responsible for the misdiagnosis of tuberculosis, but its impact on other
      contexts has not been analyzed. We present the findings of a molecular
      epidemiology analysis in which the recent transmission events identified by a
      genotyping reference center were overestimated as a result of unnoticed
      laboratory cross-contamination in the original diagnostic laboratories.

PMID- 16891519
TI  - Short-sequence-repeat analysis of Mycobacterium avium subsp. paratuberculosis and
      Mycobacterium avium subsp. avium isolates collected from animals throughout the
      United States reveals both stability of loci and extensive diversity.
AB  - We analyzed the multilocus short sequence repeats (SSRs) of 211 and 56 isolates
      of Mycobacterium avium subsp. paratuberculosis and M. avium subsp. avium,
      respectively. The M. avium subsp. paratuberculosis isolates could be
      differentiated into 61 genotypes. The M. avium subsp. avium isolates showed
      limited diversity. These SSRs are stable and suitable for studying the molecular
      epidemiology of M. avium subsp. paratuberculosis.

PMID- 16891520
TI  - Identification of Acinetobacter baumannii by detection of the blaOXA-51-like
      carbapenemase gene intrinsic to this species.
AB  - bla(OXA-51-like) was sought in clinical isolates of Acinetobacter species in a
      multiplex PCR, which also detects bla(OXA-23-like) and class 1 integrase genes.
      All isolates that gave a band for bla(OXA-51-like) identified as A. baumannii.
      This gene was detected in each of 141 isolates of A. baumannii but not in those
      of 22 other Acinetobacter species.

PMID- 16891521
TI  - Identification of Histoplasma capsulatum, Blastomyces dermatitidis, and
      Coccidioides species by repetitive-sequence-based PCR.
AB  - The performance of repetitive-sequence-based PCR (rep-PCR) using the DiversiLab
      system for identification of Coccidioides species, Blastomyces dermatitidis, and
      Histoplasma capsulatum was assessed by comparing data obtained to colony
      morphology and microscopic characteristics and to nucleic acid probe results. DNA
      from cultures of 23 Coccidioides, 24 B. dermatitidis, 24 H. capsulatum, 3
      Arthrographis, and 2 Malbranchea isolates was extracted using a microbial DNA
      isolation kit as recommended by Bacterial Barcodes, Inc. Rep-PCR and probe
      results agreed for 97.2% of the dimorphic fungi when > or =85% similarity was
      used as the criterion for identification. Two H. capsulatum isolates were not
      identified, but no isolates were misidentified. From 43 of those cultures (15
      Coccidioides, 14 B. dermatitidis, 14 H. capsulatum, 3 Arthrographis, and 2
      Malbranchea), DNA also was extracted using an IDI lysis kit, a simpler method.
      Rep-PCR and probe results agreed for 97.7% of the dimorphic fungi when a
      criterion of > or =90% similarity was used for identification. One H. capsulatum
      isolate could not be identified; no isolates were misidentified. Using > or =85%
      similarity for identification resulted in one misidentification. These data
      suggest that the DiversiLab system can be used to identify Coccidioides and B.
      dermatitidis and, possibly, H. capsulatum isolates.

PMID- 16891522
TI  - Comparison of real-time PCR assays for monitoring serum hepatitis B virus DNA
      levels during antiviral therapy.
AB  - The performance characteristics of the RealART and Molecular Beacons assays were
      compared with those of the Digene Hybrid Capture II assay (ultrasensitive). The
      results of the RealART and Digene Hybrid assays were related (r = 0.94; P <
      0.001) and diverged by 2 orders of magnitude. The RealART assay can be used to
      effectively monitor serum hepatitis B virus DNA levels.

PMID- 16891523
TI  - Comparison of dalbavancin MIC values determined by Etest (AB BIODISK) and
      reference dilution methods using gram-positive organisms.
AB  - While standardized microdilution testing methodologies and quality control ranges
      exist for the novel glycolipopeptide dalbavancin, no testing methods have been
      described that are immediately available for routine use in clinical
      laboratories. In this study, we found that the dalbavancin Etest (AB BIODISK,
      Solna, Sweden) procedure demonstrated a high degree of agreement (100% within +/
      2 log(2) dilution steps) with the standardized broth microdilution method,
      validating the use of the Etest as an alternative test for investigational or
      clinical purposes following regulatory approval.

PMID- 16891524
TI  - Evaluation of two new immunochromatographic assays (Rapid U Legionella antigen
      test and SD Bioline Legionella antigen test) for detection of Legionella
      pneumophila serogroup 1 antigen in urine.
AB  - We evaluated two new immunochromatographic assays for their abilities to detect
      Legionella pneumophila serogroup 1 antigen in urine. The results were compared
      with those obtained by the Binax NOW urinary antigen test. The sensitivities and
      specificities were estimated to be 71.2% and 96.6%, respectively, for the Rapid U
      test; 31.5% and 98.9%, respectively, for the SD Bioline test; and 91.8% and 100%,
      respectively, for the Binax NOW test.

PMID- 16891525
TI  - Multiple cases of familial transmission of community-acquired methicillin
      resistant Staphylococcus aureus.
AB  - The worldwide emergence of community-acquired methicillin-resistant
      Staphylococcus aureus (CA-MRSA) can have severe public health implications.
      Familial transmissions of CA-MRSA in The Netherlands were investigated. Among the
      families studied, two clusters of CA-MRSA could be identified. This report
      demonstrates that family members can serve as reservoirs of CA-MRSA which may
      become a serious problem in containing the spread of MRSA.

PMID- 16891526
TI  - Asymptomatic norovirus infection in Mexican children.
AB  - Sixty-three children in periurban Mexico City were examined for the occurrence of
      asymptomatic norovirus (NoV) infection from June to August 1998. NoV was detected
      in 48 of 161 stool specimens (29.8%), with 31 children (49.2%) having at least
      one positive stool. Asymptomatic NoV infection occurred commonly during
      summertime in a Mexican pediatric population.

PMID- 16891528
TI  - Use of an immunochromatographic dipstick test for rapid detection of Trypanosoma
      cruzi in sera from animal reservoir hosts.
AB  - We evaluated an immunochromatographic dipstick test to detect Trypanosoma cruzi
      in canine serum samples from areas of endemicity (n = 141) and nonendemicity (n =
      28) for Chagas' disease with known serological and xenodiagnostic test results.
      The dipstick test had a specificity of at least 94% and a sensitivity of at least
      96%. The dipstick tested could become the first choice for screening purposes in
      disease surveillance or intervention programs.

PMID- 16891527
TI  - Identification of genotypes of Enterocytozoon bieneusi from stool samples from
      human immunodeficiency virus-infected patients in Thailand.
AB  - We identified genotypes of Enterocytozoon bieneusi from 33 stool samples of Thai
      human immunodeficiency virus (HIV)-infected adult patients. Genotype D was
      identified at the highest frequency (36.4%), while genotype E was the second most
      common (15.1%). Genotypes O and PigEBITS 7, previously found only in pigs, were
      observed in Thai HIV-infected patients. Phylogenetic analysis supported a
      zoonotic nature for E. bieneusi.

PMID- 16891529
TI  - Pyrosequencing as a rapid tool for identification of GES-type extended-spectrum
      beta-lactamases.
AB  - A pyrosequencing technique was used for identification of extended-spectrum beta
      lactamases (ESBLs) of GES type. These beta-lactamases are isolated increasingly
      emerging in gram-negative bacteria worldwide. This rapid and reliable
      identification method is interesting, since GES variants, including not only
      expanded-spectrum cephalosporins but also carbapenems, cephamycins, and
      monobactams, are the only ESBLs that possess different hydrolysis profiles.

PMID- 16891530
TI  - Widely distributed and predominant CTX-M extended-spectrum beta-lactamases in
      Amsterdam, The Netherlands.
AB  - Three hundred sixty Enterobacteriaceae and nonfermenting gram-negative bacilli,
      isolated during one week in May 2004 at five hospitals in Amsterdam, The
      Netherlands, were evaluated for the presence of extended-spectrum beta-lactamases
      (ESBLs). A prevalence of 7.8% was found, in contrast to the 1% observed in 1997.
      CTX-M ESBLs dominated, and four types were identified in 18 isolates.

PMID- 16891531
TI  - Genetic diversity of competence gene loci in clinical genotypes of Streptococcus
      mutans.
AB  - The frequencies of 21 competence genes were analyzed in 94 genotypes of
      Streptococcus mutans. These include those of a main regulatory system (comCDE),
      structural, and other regulatory orthologues identified in the genome of strain
      UA159. PCR and Southern blot analysis revealed that all genes are widespread
      within the species.

PMID- 16891532
TI  - False-positive results of enzyme immunoassays for human immunodeficiency virus in
      patients with uncomplicated malaria.
AB  - Malaria may impact upon human immunodeficiency virus (HIV) test results. We
      evaluated two HIV enzyme immunoassays (EIAs) by testing 1,965 Ugandans with
      malaria. We found poor positive predictive values (53% and 76%), particularly
      with younger age. Combining EIAs eliminated false positives but missed 21% of
      true positives. Performance of HIV EIAs in malaria may be unsatisfactory.

PMID- 16891533
TI  - Evaluation of the GenoType Mycobacteria Direct assay for detection of
      Mycobacterium tuberculosis complex and four atypical mycobacterial species in
      clinical samples.
AB  - We evaluated GenoType Mycobacteria Direct (GTMD), a novel commercial assay based
      on nucleic acid sequence-based amplification technology, for the detection of
      Mycobacterium tuberculosis complex, M. avium, M. intracellulare, M. kansasii, and
      M. malmoense directly from clinical specimens. A total of 134 respiratory and
      extrapulmonary samples from 65 patients were processed. Sensitivity, specificity,
      positive predictive, and negative predictive values for GTMD were 92, 100, 100,
      and 77%, respectively. The GMTD technique is useful, reliable, and rapid when
      used during the normal routine of a clinical laboratory.

PMID- 16891534
TI  - Clinical evaluation of a type III secretion system real-time PCR assay for
      diagnosing melioidosis.
AB  - A Burkholderia pseudomallei type III secretion system real-time PCR assay was
      evaluated on clinical specimens in a region where melioidosis is endemic. The PCR
      was positive in 30/33 (91%) patients with culture-confirmed melioidosis. All six
      patients with melioidosis septic shock were blood PCR positive, suggesting
      potential for rapid diagnosis and commencement of appropriate therapy.

PMID- 16891535
TI  - Bacteremia caused by Solobacterium moorei in a patient with acute proctitis and
      carcinoma of the cervix.
AB  - We describe a case of Solobacterium moorei bacteremia in a 43-year-old woman
      presenting with acute proctitis complicating radiotherapy for cervical carcinoma.
      Phenotypic tests failed to identify the bacterium, which was subsequently
      identified by 16S rRNA gene sequencing. 16S rRNA gene sequencing could help
      better define the pathogenicity of S. moorei.

PMID- 16891536
TI  - Catheter-related fungemia due to Candida thermophila.
AB  - We report a case of bloodstream infection caused by Candida thermophila, a yeast
      not previously associated with human disease. The infection occurred in a 13-year
      old boy with medulloblastoma who presented with 1 day of fever. Multiple blood
      cultures were positive for yeast. Removal of the catheter resulted in prompt
      resolution of the fever and sterilization of the blood cultures. The species was
      identified by sequencing domains 1 and 2 of the large subunit rRNA gene.
      Antifungal susceptibility testing was also performed.

PMID- 16891537
TI  - Community-acquired meningitis and sepsis caused by Chryseobacterium
      meningosepticum in a patient diagnosed with thalassemia major.
AB  - Chryseobacterium meningosepticum is a rare pathogen in cases of bacterial
      meningitis in adults and adolescents. We report on the case history of a 17-year
      old boy with thalassemia major and meningitis and sepsis caused by C.
      meningosepticum in splenectomized. The patient received vancomycin therapy for 21
      days and was discharged in a state of complete recovery.

PMID- 16891539
TI  - Nucleotide sequencing for diagnosis of sinusal infection by Schizophyllum
      commune, an uncommon pathogenic fungus.
AB  - Schizophyllum commune, a basidiomycete fungus, is a rare cause of mycotic
      disease. We report here a case of sinusitis in a 35-year-old woman that
      underscores the value of molecular biology for the diagnosis of this fungal
      infection.

PMID- 16891538
TI  - Ciprofloxacin treatment of bacterial peritonitis associated with chronic
      ambulatory peritoneal dialysis caused by Neisseria cinerea.
AB  - Bacterial peritonitis is a well-recognized complication of chronic ambulatory
      peritoneal dialysis (CAPD) in patients with end-stage renal failure. We present a
      case of peritonitis due to an unusual pathogen, Neisseria cinerea, unresponsive
      to the standard intraperitoneal (i.p.) vancomycin and gentamicin, which responded
      rapidly to oral ciprofloxacin.

PMID- 16891540
TI  - Molecular identification of Leuconostoc mesenteroides as a cause of brain abscess
      in an immunocompromised patient.
AB  - Leuconostoc species are emerging pathogens that can cause severe infections,
      particularly in immunocompromised patients. Using molecular methods, we
      identified Leuconostoc mesenteroides as the cause of a brain abscess which was
      successfully treated by surgery and antimicrobial treatment. This is the first
      report of brain abscess caused by this species.

PMID- 16891541
TI  - Azole resistance of Candida glabrata in a case of recurrent fungemia.
AB  - We describe a case of recurrent Candida glabrata fungemia that became
      unresponsive to fluconazole treatment. Posttreatment isolates from blood and
      vaginal cultures of the immunocompetent patient were azole resistant and
      exhibited upregulated expression of CgCDR1/CgCDR2 efflux pumps compared to the
      original isolates. Amphotericin B therapy eradicated the infection.

PMID- 16891543
TI  - Is there an optimal genetic target for molecular analysis of hepatitis B virus
      transmission?

PMID- 16891542
TI  - First report of bacteremia by Asaia bogorensis, in a patient with a history of
      intravenous-drug abuse.
AB  - We report the first documented case of bacteremia caused by Asaia bogorensis in a
      young patient with a history of intravenous-drug abuse. A. bogorensis was
      identified by sequencing the 16S rRNA gene. The isolate was exceptionally
      resistant to almost all antibiotics that are routinely tested for gram-negative
      rods but was susceptible to netilmicin, gentamicin, and doxycycline.

PMID- 16891544
TI  - Whole-genome analysis of Oryza sativa reveals similar architecture of two
      component signaling machinery with Arabidopsis.
AB  - The two-component system (TCS), which works on the principle of histidine
      aspartate phosphorelay signaling, is known to play an important role in diverse
      physiological processes in lower organisms and has recently emerged as an
      important signaling system in plants. Employing the tools of bioinformatics, we
      have characterized TCS signaling candidate genes in the genome of Oryza sativa L.
      subsp. japonica. We present a complete overview of TCS gene families in O.
      sativa, including gene structures, conserved motifs, chromosome locations, and
      phylogeny. Our analysis indicates a total of 51 genes encoding 73 putative TCS
      proteins. Fourteen genes encode 22 putative histidine kinases with a conserved
      histidine and other typical histidine kinase signature sequences, five
      phosphotransfer genes encoding seven phosphotransfer proteins, and 32 response
      regulator genes encoding 44 proteins. The variations seen between gene and
      protein numbers are assumed to result from alternative splicing. These putative
      proteins have high homology with TCS members that have been shown experimentally
      to participate in several important physiological phenomena in plants, such as
      ethylene and cytokinin signaling and phytochrome-mediated responses to light. We
      conclude that the overall architecture of the TCS machinery in O. sativa and
      Arabidopsis thaliana is similar, and our analysis provides insights into the
      conservation and divergence of this important signaling machinery in higher
      plants.

PMID- 16891545
TI  - Transgenic tobacco plants overexpressing chitinases of fungal origin show
      enhanced resistance to biotic and abiotic stress agents.
AB  - Genes encoding defense-related proteins have been used to alter the resistance of
      plants to pathogens and other environmental challenges, but no single fungal gene
      overexpression has produced broad-spectrum stress resistance in transgenic lines.
      We have generated transgenic tobacco (Nicotiana tabacum) lines that overexpress
      the endochitinases CHIT33 and CHIT42 from the mycoparasitic fungus Trichoderma
      harzianum and have evaluated their tolerance to biotic and abiotic stress. Both
      CHIT33 and CHIT42, individually, conferred broad resistance to fungal and
      bacterial pathogens, salinity, and heavy metals. Such broad-range protective
      effects came off with no obvious detrimental effect on the growth of tobacco
      plants.

PMID- 16891546
TI  - IMMUTANS does not act as a stress-induced safety valve in the protection of the
      photosynthetic apparatus of Arabidopsis during steady-state photosynthesis.
AB  - IMMUTANS (IM) encodes a thylakoid membrane protein that has been hypothesized to
      act as a terminal oxidase that couples the reduction of O(2) to the oxidation of
      the plastoquinone (PQ) pool of the photosynthetic electron transport chain.
      Because IM shares sequence similarity to the stress-induced mitochondrial
      alternative oxidase (AOX), it has been suggested that the protein encoded by IM
      acts as a safety valve during the generation of excess photosynthetically
      generated electrons. We combined in vivo chlorophyll fluorescence quenching
      analyses with measurements of the redox state of P(700) to assess the capacity of
      IM to compete with photosystem I for intersystem electrons during steady-state
      photosynthesis in Arabidopsis (Arabidopsis thaliana). Comparisons were made
      between wild-type plants, im mutant plants, as well as transgenics in which IM
      protein levels had been overexpressed six (OE-6 x) and 16 (OE-16 x) times.
      Immunoblots indicated that IM abundance was the only major variant that we could
      detect between these genotypes. Overexpression of IM did not result in increased
      capacity to keep the PQ pool oxidized compared to either the wild type or im
      grown under control conditions (25 degrees C and photosynthetic photon flux
      density of 150 micromol photons m(-2) s(-1)). Similar results were observed
      either after 3-d cold stress at 5 degrees C or after full-leaf expansion at 5
      degrees C and photosynthetic photon flux density of 150 micromol photons m(-2) s(
      1). Furthermore, IM abundance did not enhance protection of either photosystem II
      or photosystem I from photoinhibition at either 25 degrees C or 5 degrees C. Our
      in vivo data indicate that modulation of IM expression and polypeptide
      accumulation does not alter the flux of intersystem electrons to P(700)(+) during
      steady-state photosynthesis and does not provide any significant photoprotection.
      In contrast to AOX1a, meta-analyses of published Arabidopsis microarray data
      indicated that IM expression exhibited minimal modulation in response to myriad
      abiotic stresses, which is consistent with our functional data. However, IM
      exhibited significant modulation in response to development in concert with
      changes in AOX1a expression. Thus, neither our functional analyses of the IM
      knockout and overexpression lines nor meta-analyses of gene expression support
      the model that IM acts as a safety valve to regulate the redox state of the PQ
      pool during stress and acclimation. Rather, IM appears to be strongly regulated
      by developmental stage of Arabidopsis.

PMID- 16891547
TI  - Galactoglucomannans increase cell population density and alter the
      protoxylem/metaxylem tracheary element ratio in xylogenic cultures of Zinnia.
AB  - Xylogenic cultures of zinnia (Zinnia elegans) provide a unique opportunity to
      study signaling pathways of tracheary element (TE) differentiation. In vitro TEs
      differentiate into either protoxylem (PX)-like TEs characterized by
      annular/helical secondary wall thickening or metaxylem (MX)-like TEs with
      reticulate/scalariform/pitted thickening. The factors that determine these
      different cell fates are largely unknown. We show here that supplementing zinnia
      cultures with exogenous galactoglucomannan oligosaccharides (GGMOs) derived from
      spruce (Picea abies) xylem had two major effects: an increase in cell population
      density and a decrease in the ratio of PX to MX TEs. In an attempt to link these
      two effects, the consequence of the plane of cell division on PX-MX
      differentiation was assessed. Although GGMOs did not affect the plane of cell
      division per se, they significantly increased the proportion of longitudinally
      divided cells differentiating into MX. To test the biological significance of
      these findings, we have determined the presence of mannan-containing
      oligosaccharides in zinnia cultures in vitro. Immunoblot assays indicated that
      beta-1,4-mannosyl epitopes accumulate specifically in TE-inductive media. These
      epitopes were homogeneously distributed within the thickened secondary walls of
      TEs when the primary cell wall was weakly labeled. Using polysaccharide analysis
      carbohydrate gel electrophoresis, glucomannans were specifically detected in cell
      walls of differentiating zinnia cultures. Finally, zinnia macroarrays probed with
      cDNAs from cells cultured in the presence or absence of GGMOs indicated that
      significantly more genes were down-regulated rather than up-regulated by GGMOs.
      This study constitutes a major step in the elucidation of signaling mechanisms of
      PX- and MX-specific genetic programs in zinnia.

PMID- 16891548
TI  - Quantitative profiling of Arabidopsis polar glycerolipids in response to
      phosphorus starvation. Roles of phospholipases D zeta1 and D zeta2 in
      phosphatidylcholine hydrolysis and digalactosyldiacylglycerol accumulation in
      phosphorus-starved plants.
AB  - Phosphorus is an essential macronutrient that often limits plant growth and
      development. Under phosphorus-limited conditions, plants undergo substantial
      alterations in membrane lipid composition to cope with phosphorus deficiency. To
      characterize the changes in lipid species and to identify enzymes involved in
      plant response to phosphorus starvation, 140 molecular species of polar
      glycerolipids were quantitatively profiled in rosettes and roots of wild-type
      Arabidopsis (Arabidopsis thaliana) and phospholipase D knockout mutants pld
      zeta1, pld zeta2, and pld zeta1 pld zeta2. In response to phosphorus starvation,
      the concentration of phospholipids was decreased and that of galactolipids was
      increased. Phospholipid lost in phosphorus-starved Arabidopsis rosettes was
      replaced by an equal amount of galactolipid. The concentration of phospholipid
      lost in roots was much greater than in rosettes. Disruption of both PLD zeta1 and
      PLD zeta2 function resulted in a smaller decrease in phosphatidylcholine and a
      smaller increase in digalactosyldiacylglycerol in phosphorus-starved roots. The
      results suggest that hydrolysis of phosphatidylcholine by PLD zetas during
      phosphorus starvation contributes to the supply of inorganic phosphorus for cell
      metabolism and diacylglycerol moieties for galactolipid synthesis.

PMID- 16891549
TI  - Dehydroascorbate reductase affects leaf growth, development, and function.
AB  - Ascorbic acid (Asc) is a major antioxidant in plants that detoxifies reactive
      oxygen species (ROS) and maintains photosynthetic function. Expression of
      dehydroascorbate reductase (DHAR), responsible for regenerating Asc from an
      oxidized state, regulates the cellular Asc redox state, which in turn affects
      cell responsiveness and tolerance to environmental ROS. Because of its role in
      Asc recycling, we examined whether DHAR is important for plant growth.
      Suppression of DHAR expression resulted in a preferential loss of chlorophyll a,
      a lower steady state of Rubisco as measured by the amount of the large subunit of
      Rubisco (RbcL), and a lower rate of CO(2) assimilation. As a consequence, a
      slower rate of leaf expansion and reduced foliar dry weight were observed. In
      addition, an accelerated rate of loss of chlorophyll, RbcL, light-harvesting
      complex II, and photosynthetic functioning was observed in mature leaves,
      resulting in premature leaf aging. Reduced growth rate as measured by plant
      height and leaf number was consistent with the DHAR-mediated reduction of
      photosynthetic function. Increasing DHAR expression maintained higher levels of
      chlorophyll, RbcL, light-harvesting complex II, and photosynthetic functioning,
      resulting in delayed leaf aging. The effect of DHAR expression on leaf aging
      inversely correlated with the level of lipid peroxidation, indicating that DHAR
      functions to protect against ROS-mediated damage. These observations support the
      conclusion that through its Asc recycling function, DHAR affects the level of
      foliar ROS and photosynthetic activity during leaf development and as a
      consequence, influences the rate of plant growth and leaf aging.

PMID- 16891550
TI  - Adenosine kinase modulates root gravitropism and cap morphogenesis in
      Arabidopsis.
AB  - Adenosine kinase (ADK) is a key enzyme that regulates intra- and extracellular
      levels of adenosine, thereby modulating methyltransferase reactions, production
      of polyamines and secondary compounds, and cell signaling in animals.
      Unfortunately, little is known about ADK's contribution to the regulation of
      plant growth and development. Here, we show that ADK is a modulator of root cap
      morphogenesis and gravitropism. Upon gravistimulation, soluble ADK levels and
      activity increase in the root tip. Mutation in one of two Arabidopsis
      (Arabidopsis thaliana) ADK genes, ADK1, results in cap morphogenesis defects,
      along with alterations in root sensitivity to gravistimulation and slower
      kinetics of root gravitropic curvature. The kinetics defect can be partially
      rescued by adding spermine to the growth medium, whereas the defects in cap
      morphogenesis and gravitropic sensitivity cannot. The root morphogenesis and
      gravitropism defects of adk1-1 are accompanied by altered expression of the PIN3
      auxin efflux facilitator in the cap and decreased expression of the auxin
      responsive DR5-GUS reporter. Furthermore, PIN3 fails to relocalize to the bottom
      membrane of statocytes upon gravistimulation. Consequently, adk1-1 roots cannot
      develop a lateral auxin gradient across the cap, necessary for the curvature
      response. Interestingly, adk1-1 does not affect gravity-induced cytoplasmic
      alkalinization of the root statocytes, suggesting either that ADK1 functions
      between cytoplasmic alkalinization and PIN3 relocalization in a linear pathway or
      that the pH and PIN3-relocalization responses to gravistimulation belong to
      distinct branches of the pathway. Our data are consistent with a role for ADK and
      the S-adenosyl-L-methionine pathway in the control of root gravitropism and cap
      morphogenesis.

PMID- 16891551
TI  - Chimeric proteins suggest that the catalytic and/or C-terminal domains give CesA1
      and CesA3 access to their specific sites in the cellulose synthase of primary
      walls.
AB  - CesA1 and CesA3 are thought to occupy noninterchangeable sites in the cellulose
      synthase making primary wall cellulose in Arabidopsis (Arabidopsis thaliana L.
      Heynh). With domain swaps and deletions, we show that sites C terminal to
      transmembrane domain 2 give CesAs access to their individual sites and, from
      dominance and recessive behavior, deduce that certain CesA alleles exclude others
      from accessing each site. Constructs that swapped or deleted N-terminal domains
      were stably transformed into the wild type and into the temperature-sensitive
      mutants rsw1 (Ala-549Val in CesA1) and rsw5 (Pro-1056Ser in CesA3). Dominant
      positive behavior was assayed as root elongation at the restrictive temperature
      and dominant-negative effects were observed at the permissive temperature. A
      protein with the catalytic and C-terminal domains of CesA1 and the N-terminal
      domain of CesA3 promoted growth only in rsw1 consistent with it accessing the
      CesA1 site even though it contained the CesA3 N-terminal domain. A protein having
      the CesA3 catalytic and C-terminal domains linked to the CesA1 N-terminal domain
      dramatically affected growth, but only in the CesA3 mutant. This is consistent
      with the operation of the same access rule taking this chimeric protein to the
      CesA3 site. In this case, however, the transgene behaved as a genotype-specific
      dominant negative, causing a 60% death rate in rsw5, but giving no visible
      phenotype in wild type or rsw1. We therefore hypothesize that possession of
      CesA3(WT) protects Columbia and rsw1 from the lethal effects of this chimeric
      protein, whereas the mutant protein (CesA3(rsw5)) does not.

PMID- 16891552
TI  - The frequency and efficiency of endogene suppression by transitive silencing
      signals is influenced by the length of sequence homology.
AB  - Transitivity, the spread of RNA silencing along primary target sequences, leads
      to the degradation of secondary targets that have no sequence homology to the
      initial silencing trigger. We demonstrate that increasing the distance between
      direct and adjacent target sequences in a transgenic primary target delays the
      onset of silencing of a secondary target gene. Silencing can spread in a 3' to 5'
      direction over a distance of at least 500 nucleotides (nt), but this requires
      consistently more time compared to a distance of 98 nt or 250 nt. The efficiency
      and frequency of transitive silencing of an endogene depends on the length of its
      sequence homology with the primary target. With a length of 500 nt, efficient
      silencing can eventually be established in all plants, whereas lengths of 250 nt
      and 98 nt homology result in less efficient and less frequent suppression. These
      results suggest that amplification of secondary small interfering RNAs (siRNAs)
      is a time-requiring process that gradually expands the population of siRNAs until
      a steady-state level is reached. Moreover, the length of the sequence homology in
      the primary target providing secondary siRNAs determines whether this steady
      state level readily exceeds the threshold necessary for efficient silencing.

PMID- 16891553
TI  - Receptor signal output mediated by the ETR1 N terminus is primarily subfamily I
      receptor dependent.
AB  - etr1-1 is a dominant ethylene receptor gene in Arabidopsis (Arabidopsis thaliana)
      and confers ethylene insensitivity. The truncated etr1-1(1-349) protein is
      capable of repressing ethylene responses, whereas etr1(1-349) is not, lending
      support to a hypothesis that the dominant etr1-1(1-349) could convert wild-type
      receptors to an ethylene-insensitive state. Assuming that etr1-1(1-349) and
      etr1(1-349) would share the same signaling mechanism, we hypothesize that the
      etr1(1-349) protein is capable of repressing ethylene responses when not bound
      with ethylene. In this study, we show that both etr1(1-349) and etr1-1(1-349) are
      capable of receptor signal output, which is primarily dependent on subfamily I
      receptors. The etr1(1-349) and etr1-1(1-349) clones were individually transformed
      to mutants and the resulting phenotypes were scored. Each of those transgenes
      restored the rosette growth and flower fertility of etr1-7 ers1-2 to a similar
      extent. In contrast, neither etr1(1-349) nor etr1-1(1-349) was capable of signal
      output in etr1-7 ers1-3. The ERS1 transcript was detectable in ers1-2 but not in
      ers1-3, implying that ETR1 N-terminal signaling is subfamily I dependent. Loss of
      the subfamily II receptor genes did not perturb etr1-1(1-349)-mediated ethylene
      insensitivity. Possible roles of subfamily I receptors and disulfide linkages in
      ETR1 receptor signal output mediated through the N terminus are discussed.

PMID- 16891555
TI  - Comparative psychoneuroimmunology: evidence from the insects.
AB  - Interactions between immune systems, nervous systems, and behavior are well
      established in vertebrates. A comparative examination of these interactions in
      other animals will help us understand their evolution and present adaptive
      functions. Insects show immune-behavioral interactions similar to those seen in
      vertebrates, suggesting that many of them may have a highly conserved function.
      Activation of an immune response in insects results in illness-induced anorexia,
      behavioral fever, changes in reproductive behavior, and decreased learning
      ability in a broad range of species. Flight-or-fight behaviors result in a
      decline in disease resistance. In insects, illness-induced anorexia may enhance
      immunity. Stress-induced immunosuppression is probably due to physiological
      conflicts between the immune response and those of other physiological processes.
      Because insects occupy a wide range of ecological niches, they will be useful in
      examining how some immune-behavioral interactions are sculpted by an animal's
      behavioral ecology.

PMID- 16891554
TI  - Reading words in discourse: the modulation of lexical priming effects by message
      level context.
AB  - Repetition and semantic-associative priming effects have been demonstrated for
      words in nonstructured contexts (i.e., word pairs or lists of words) in numerous
      behavioral and electrophysiological studies. The processing of a word has thus
      been shown to benefit from the prior presentation of an identical or associated
      word in the absence of a constraining context. An examination of such priming
      effects for words that are embedded within a meaningful discourse context
      provides information about the interaction of different levels of linguistic
      analysis. This article reviews behavioral and electrophysiological research that
      has examined the processing of repeated and associated words in sentence and
      discourse contexts. It provides examples of the ways in which eye tracking and
      event-related potentials might be used to further explore priming effects in
      discourse. The modulation of lexical priming effects by discourse factors
      suggests the interaction of information at different levels in online language
      comprehension.

PMID- 16891556
TI  - Neuroimaging, cognitive, and neurobehavioral outcomes following carbon monoxide
      poisoning.
AB  - Carbon monoxide is a colorless, odorless gas produced as a byproduct of
      combustion. Carbon monoxide is the leading cause of poisoning injury and death
      worldwide. Morbidity following CO poisoning includes neurologic sequelae,
      neuropathologic abnormalities on brain imaging, neurobehavioral changes, and
      cognitive impairments. It is estimated that as high as 50% of individuals with
      carbon monoxide poisoning will develop neurologic, neurobehavioral, or cognitive
      sequelae. Carbon monoxide related cognitive impairments included impaired memory,
      attention, executive function, motor, visual spatial, and slow mental processing
      speed. Given the high rate of brain related morbidity and the fact that the
      majority of carbon monoxide is avoidable, awareness and prevention of carbon
      monoxide poisoning is warranted.

PMID- 16891557
TI  - Predictors of posttraumatic stress in police and other first responders.
AB  - We provide an overview of previous research conducted by our group on risk and
      resilience factors for PTSD symptoms in police and other first responders. Based
      on our work, the findings of other investigators on individual differences in
      risk for PTSD, and drawing on preclinical studies fear conditioning and
      extinction, we propose a conceptual model for the development of PTSD symptoms
      emphasizing the role of vulnerability and resilience to peritraumatic panic
      reactions. We tested this conceptual model in a cross-sectional sample of police
      officers (n = 715). Utilizing an hierarchical linear regression model we were
      able to explain 39.7% of the variance in PTSD symptoms. Five variables remained
      significant in the final model; greater peritraumatic distress (beta = 0.240, P <
      .001), greater peritraumatic dissociation (beta = 0.174, P < .001), greater
      problem-solving coping (beta = 0.103, P < .01), greater routine work environment
      stress (beta = 0.182, P < .001), and lower levels of social support (beta = 
      0.246, P < .001). These results were largely consistent with the proposed
      conceptual model. Next steps in this line of research will be to test this model
      prospectively in a sample of 400 police academy recruits assessed during training
      and currently being followed for the first 2 years of police service.

PMID- 16891558
TI  - Longitudinal psychophysiological studies of heart rate: mediating effects and
      implications for treatment.
AB  - Fear conditioning models of posttraumatic stress disorder (PTSD) propose that
      noradrenergic activation at the time of trauma leads to over-consolidation of
      trauma memories and contributes to PTSD. This model suggests that resting heart
      rate (HR) in the acute phase after trauma may reflect the strength of the
      noradrenergic response and may represent an initial marker of those who are at
      risk of PTSD development. Ten prospective studies are reported that assessed the
      relationship of resting HR within 1 week of trauma and subsequent PTSD. Whereas 8
      of the 10 studies found that elevated HR in the acute phase was associated with
      increased risk of subsequent PTSD, there was much variability in the HR levels
      and subsequent PTSD. The current data suggest multiple pathways to PTSD
      development that may not necessarily involve elevated HR. The data indicate that
      HR in the acute phase cannot be accurately used to identify people who are at
      risk for PTSD. The association between HR and PTSD does suggest that HR is a
      useful means to test fear conditioning models of trauma response.

PMID- 16891559
TI  - Predicting PTSD prospectively based on prior trauma history and immediate
      biological responses.
AB  - Studies examining the biopsychology of posttraumatic stress disorder (PTSD) have
      suggested that PTSD is characterized by alterations of the primary stress
      pathways: the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic
      nervous system (SNS). More recent investigations point to the presence of these
      alterations soon after a traumatic event, leading researchers to suggest that
      acute biological responses may serve as risk or resilience factors for the
      development of PTSD. The present article reviews the evidence for early
      biological predictors of PTSD, with a focus on the role of prior trauma as a
      contributor to both hormonal abnormalities and increased risk for the development
      of PTSD following a subsequent trauma.

PMID- 16891560
TI  - Separation anxiety as a mediator between acute morphine administration and PTSD
      symptoms in injured children.
AB  - Emerging evidence suggests that individuals who receive morphine while
      hospitalized demonstrate a decrease in symptoms of posttraumatic stress disorder
      (PTSD). However, the mechanisms of effects are not yet well understood. The goal
      of the current study was to examine three possible mediators for this effect.
      Sixty-one injured (burns, motor vehicle accidents, falls, and assaults) children
      were assessed during hospitalization and again 3 months post discharge.
      Assessment included acute and follow-up child report measures of pain, PTSD, and
      anxiety symptoms, as well as a medical record review for medication
      administration and pulse during hospitalization. Pathway analyses were conducted
      to test the potential mediating roles of pain reduction, noradrenergic
      attenuation, and separation anxiety on the association between morphine and PTSD.
      Results suggest that a reduction in separation anxiety may mediate the
      association between morphine administration and PTSD symptom reduction at 3
      months. These findings have implications for our understanding of morphine's
      effects on psychological functioning following an acute injury and for direct
      clinical care.

PMID- 16891561
TI  - Efficacy of hydrocortisone in preventing posttraumatic stress disorder following
      critical illness and major surgery.
AB  - Like other humans exposed to extreme trauma, patients who have been treated in an
      intensive care unit (ICU) often report traumatic memories. Extremely traumatic
      memories from the ICU in some of these patients are associated with the
      development of posttraumatic stress disorder (PTSD), which results in significant
      impairments in health-related quality of life (HRQL) outcomes of ICU therapy.
      Severely ill patients in the ICU often show insufficient endogenous
      glucocorticoid signaling, which has recently been termed critical illness-related
      corticosteroid insufficiency (CIRCI). We performed several controlled trials in
      ICU patients with suspected CIRCI from septic shock or cardiac surgery, which
      indicated that the administration of glucocorticoids (stress doses of
      hydrocortisone) during ICU treatment results in a significant reduction of PTSD
      symptoms in long-term survivors as well as improvements in HRQL outcomes. Stress
      doses of hydrocortisone could help to surmount impaired glucocorticoid signaling
      from CIRCI during critical illness resulting in a downregulation of the stress
      response as well as inhibition of traumatic memory retrieval and facilitated
      extinction of aversive information.

PMID- 16891562
TI  - Memory performance in older trauma survivors: implications for the longitudinal
      course of PTSD.
AB  - Impaired declarative memory performance and smaller hippocampal volume have been
      observed in young and middle-aged adults with chronic posttraumatic stress
      disorder (PTSD). These alterations may put trauma survivors with PTSD at greater
      risk for cognitive decline in later life. This article focuses on the emerging
      literature on neuropsychological impairment in aging trauma survivors, in
      particular, elderly combat veterans and survivors of the Holocaust. In veterans
      and in Holocaust survivors, PTSD was associated with substantial impairments in
      learning, free and cued recall, and recognition memory compared to the respective
      nonexposed subjects; however, in neither group was PTSD associated with impaired
      retention or "rapid forgetting." Additionally, PTSD was not associated with
      smaller right or left hippocampal volume in either cohort. PTSD is associated
      with considerable cognitive burden with age. Longitudinal studies of older
      subjects are warranted to examine whether PTSD is associated with accelerated
      aging or progressive memory loss.

PMID- 16891563
TI  - Amygdala, medial prefrontal cortex, and hippocampal function in PTSD.
AB  - The last decade of neuroimaging research has yielded important information
      concerning the structure, neurochemistry, and function of the amygdala, medial
      prefrontal cortex, and hippocampus in posttraumatic stress disorder (PTSD).
      Neuroimaging research reviewed in this article reveals heightened amygdala
      responsivity in PTSD during symptomatic states and during the processing of
      trauma-unrelated affective information. Importantly, amygdala responsivity is
      positively associated with symptom severity in PTSD. In contrast, medial
      prefrontal cortex appears to be volumetrically smaller and is hyporesponsive
      during symptomatic states and the performance of emotional cognitive tasks in
      PTSD. Medial prefrontal cortex responsivity is inversely associated with PTSD
      symptom severity. Lastly, the reviewed research suggests diminished volumes,
      neuronal integrity, and functional integrity of the hippocampus in PTSD.
      Remaining research questions and related future directions are presented.

PMID- 16891564
TI  - The relationship between cognitive and brain changes in posttraumatic stress
      disorder.
AB  - Preclinical studies show that stress is associated with changes in structure of
      the hippocampus, a brain area that plays a critical role in memory, inhibition of
      neurogenesis, and memory deficits. Studies in animals showed that both serotonin
      reuptake inhibitors (SSRIs) and the epilepsy medication phenytoin (dilantin)
      block the effects of stress on the hippocampus. Imaging studies in posttraumatic
      stress disorder (PTSD) have found smaller volume of the hippocampus as measured
      with magnetic resonance imaging (MRI) in patients with PTSD related to both
      combat and childhood abuse. These patients were also found to have deficits in
      memory on neuropsychological testing. Functional imaging studies using positron
      emission tomography (PET) found decreased hippocampal activation with memory
      tasks. In an initial study, we found that a year of treatment with paroxetine led
      to a 5% increase in hippocampal volume and a 35% increase in memory function. A
      second study showed that phenytoin was efficacious for symptoms of PTSD and led
      to a significant 6% increase in both right hippocampal and right whole brain
      volume, with no significant change in memory. These studies suggest that
      medications may counteract the effects of stress on the brain in patients with
      PTSD.

PMID- 16891565
TI  - Neuroimaging studies of emotional responses in PTSD.
AB  - Neuroimaging research offers a powerful and noninvasive means to understand
      healthy as well as dysregulated emotional processing in healthy subjects and PTSD
      patients. Functional neuroimaging findings suggest specific roles for subregions
      of the medial prefrontal (mPFC), orbito frontal (OFC), anterior cingulate (ACC),
      and insular cortices as well as the sublenticular extended amygdala (SLEA) and
      hippocampus in various components of emotional processing. Some of the same
      regions appear to be associated with emotional response to trauma, and with
      symptom formation in PTSD. Neuroimaging findings of emotional processing in
      healthy subjects and PTSD patients are discussed, addressing the specific roles
      of cortical regions like mPFC, ACC, and insula, and their potential contribution
      to PTSD pathophysiology. Processes of cognitive-emotional interactions and social
      emotions are discussed in an attempt to synthesize the prefrontal findings in
      healthy subjects and PTSD patients. Further links between functional neuroanatomy
      of emotional responses and neuroendocrine stress regulation are proposed.

PMID- 16891566
TI  - Toward a psychobiology of posttraumatic self-dysregulation: reexperiencing,
      hyperarousal, dissociation, and emotional numbing.
AB  - In this article we propose a psychobiological model that construes PTSD
      fundamentally as a disorder of affect arousal regulation. Neuroimaging studies of
      emotion regulation in psychologically healthy populations are initially reviewed
      as a framework for interpreting the results of previously published
      investigations of the neural correlates of PTSD reexperiencing and dissociation.
      We then apply the emotion regulation framework toward understanding other
      perturbed affective states in PTSD. We conclude by discussing the clinical
      significance of this framework for psychological assessment and treatment of
      posttrauma psychopathology.

PMID- 16891567
TI  - Electrophysiological responses to affective stimuli in American Indians
      experiencing trauma with and without PTSD.
AB  - American Indians are at high risk for exposure to violence and other traumatic
      events, yet few studies have investigated posttraumatic stress disorder (PTSD) or
      its neurobiological consequences in Indian communities. In the present study, a
      sample of American Indians (n = 146) were given a structured diagnostic interview
      that additionally indexed traumatic life events and symptoms emerging following
      those events. Electroencephalogram (EEG) spectra and visual event-related
      potentials (ERPs) to happy, sad, and neutral faces were also recorded from each
      participant. Ninety-nine percent of the sample had experienced at least one
      category of trauma with the mean number being 5, 27% had experienced at least 8
      categories, and 13% met DSM-IV criteria for PTSD. The PTSD group did not differ
      on any demographic or diagnostic variables from the larger sample. An
      electrophysiological signature for PTSD was found that included increases in high
      frequency gamma activity (20-40 Hz, F = 8.7, P < 0.004) in frontal leads, higher
      N1 amplitudes to sad stimuli in frontotemporal leads (F = 12.4, P < 0.001, F =
      5.0, P < 0.03), and longer latency P3 components to happy stimuli in midline,
      central, and right frontal leads (F = 4.7, P < 0.03; F = 4.1, P < 0.04; F = 4.0,
      P < 0.05). These findings were observed in participants with PTSD, but not in a
      group with equivalently high trauma counts. These findings suggest that PTSD is
      associated with EEG hyperarousal, higher attentional levels to sad stimuli, and
      slower processing of happy stimuli. They also partially confirm ERP data reported
      in combat victims with PTSD suggesting that PTSD may induce neurobiological
      consequences that transcend type of eliciting trauma as well as ethnic and
      cultural factors.

PMID- 16891568
TI  - Advances in understanding neuroendocrine alterations in PTSD and their
      therapeutic implications.
AB  - The findings from investigations of the neuroendocrinology of posttraumatic
      stress disorder (PTSD) have highlighted alterations that have not historically
      been associated with pathologic processes, and have, accordingly, raised several
      questions about the nature of the findings and their relationship to PTSD. The
      most infamous of these observations--low cortisol levels--has been the subject of
      much discussion and scrutiny because the finding has been both counterintuitive,
      and not uniformly reproducible. This fact notwithstanding, novel therapeutic
      approaches to the treatment of PTSD are in large part predicated on the
      assumption that glucocorticoid levels may be lower in PTSD. This article
      summarizes important neuroendocrine observations in cortisol and provides
      strategies for understanding what has emerged over the past two decades, to be a
      complex and sometimes contradictory literature.

PMID- 16891569
TI  - Immune function in PTSD.
AB  - Disturbed regulation of both the hypothalamic-pituitary-adrenal (HPA) axis and
      sympathoadrenomedullary system in posttraumatic stress disorder (PTSD) suggests
      that immune function, which is modulated by these systems, may also be
      dysregulated. Two dermatologic, in vivo measures of immune function, delayed-type
      hypersensitivity (DTH) and skin barrier function recovery, were examined in
      female subjects with PTSD and compared to measures in healthy female comparison
      subjects. In addition, at the time of DTH test placement, circulating numbers of
      lymphocyte subtypes were assessed. In separate studies, the effects of acute
      psychological stress on DTH and skin barrier function recovery were examined in
      healthy volunteer subjects. Both DTH and barrier function recovery were enhanced
      in women with PTSD. These findings contrast with the effects of acute stress in
      healthy control subjects, which was associated with suppression of DTH responses
      and skin barrier function recovery. There was no difference between subjects with
      PTSD and healthy control subjects in proportions of circulating lymphocyte
      subsets or in expression of the lymphocyte markers CD62, CD25, and CD45RO/CD45RA.
      These results suggest that cell-mediated immune function is enhanced in
      individuals with PTSD, a condition that imposes chronic physiologic and mental
      stress on sufferers. These findings contrast with suppression of DTH and skin
      barrier function recovery in healthy volunteers in response to acute
      psychological stress.

PMID- 16891571
TI  - Neuroendocrine regulation of sleep disturbances in PTSD.
AB  - Studies that have conducted quantitative analysis of the sleep
      electroencephalogram (EEG) have demonstrated decreased delta sleep in PTSD.
      Elevations in both hypothalamic (neurohormonal) and extrahypothalamic
      (neurotransmitter) corticotropin releasing factor (CRF) release is associated
      with decreased delta sleep activity. We present data from several studies
      examining the effect of metyrapone administration on the sleep EEG in PTSD and
      control subjects. Plasma ACTH, cortisol, and 11-deoxycorticol were obtained the
      morning following polysomnographic sleep recordings before and after metyrapone
      administration. Delta sleep was measured by period amplitude analysis. The
      results demonstrate: a) decreased delta sleep in male subjects with PTSD; b)
      metyrapone administration resulted in an activation of the sleep EEG and a robust
      decrease in quantitative delta sleep; c) the sleep and endocrine (increase in
      ACTH) responses to metyrapone were significantly decreased in PTSD in two
      different study samples; and d) the metyrapone-related disruption to sleep in
      both samples was predicted by the increase in ACTH measured the following
      morning. These findings strongly suggest that the delta sleep response to
      metyrapone is a measure of the brain response to a hypothalamic CRF challenge.
      The attenuated delta sleep and endocrine response to metyrapone challenge in PTSD
      is consistent with a model of enhanced negative feedback regulation or
      downregulation of CRF receptors in an environment of chronically increased CRF
      activity.

PMID- 16891572
TI  - Glucocorticoid-induced inhibition of memory retrieval: implications for
      posttraumatic stress disorder.
AB  - Posttraumatic stress disorder (PTSD) is characterized by traumatic memories that
      can manifest as daytime recollections, traumatic nightmares, or flashbacks in
      which components of the event are relieved. These symptoms reflect excessive
      retrieval of traumatic memories that often retain their vividness and power to
      evoke distress for decades or even a lifetime. We have reported previously that
      elevated glucocorticoid levels inhibit memory retrieval in animals and healthy
      human subjects. We therefore hypothesized that the administration of cortisol
      might also inhibit the retrieval of traumatic memories in patients with PTSD. In
      a recent pilot study, we found the first evidence to support this hypothesis.
      During a 3-month observation period, low-dose cortisol (10 mg/day) was
      administered orally for 1 month to three patients with chronic PTSD using a
      double-blind, placebo-controlled, crossover design. In each patient investigated,
      there was a significant treatment effect with cortisol-related reductions in one
      of the daily rated symptoms of traumatic memories without causing adverse side
      effects. Future studies with more patients and longer treatment periods are
      required to evaluate the efficacy of cortisol treatment for PTSD.

PMID- 16891570
TI  - Alterations in stress reactivity after long-term treatment with paroxetine in
      women with posttraumatic stress disorder.
AB  - Posttraumatic stress disorder (PTSD) is typically accompanied by both acute and
      chronic alterations in the stress response. These alterations have mostly been
      described in individuals under baseline conditions, but studies have also used a
      challenge model to assess the role of the hypothalamic-pituitary-adrenal (HPA)
      axis in the stress response. The purpose of this article was to assess the effect
      of long-term treatment with the selective reuptake inhibitor (SSRI), paroxetine,
      on stress reactivity in patients with PTSD. We assessed diurnal salivary cortisol
      and urinary cortisol as well as cortisol, heart rate, and behavioral responses to
      a standardized cognitive stress challenge, in 13 female patients with chronic
      PTSD before and after 12 months of paroxetine treatment. Treatment resulted in a
      significant decrease in PTSD symptoms. Twenty-four-hour urinary cortisol was
      lower compared to base line after successful treatment. Treatment resulted in a
      decrease of salivary cortisol levels on all time points on a diurnal curve.
      Despite similar stress perception, cortisol response to the cognitive stress
      challenge resulted in a 26.5% relative decrease in stress-induced salivary
      cortisol with treatment. These results suggest that successful treatment with
      SSRI in chronic PTSD is associated with a trend for a decrease in baseline
      diurnal cortisol and with reduced cortisol reactivity to stress.

PMID- 16891573
TI  - Neurobiological research on sleep and stress hormones in epidemiological samples.
AB  - Information on stress hormones and sleep disturbance in posttraumatic stress
      disorder (PTSD) is on the basis of clinical samples and samples of other
      selective populations. Neurobiological studies nested in a large epidemiological
      community sample were recently reported. PTSD was compared with several control
      groups, defined by exposure and by diagnostic classification on the basis of
      comorbidity with Major Depression. Key findings were: (a) higher mean
      catecholamines in persons with PTSD versus controls; (b) no difference in mean
      cortisol between groups; (c) comorbid PTSD and depression was associated with
      higher cortisol in women; and (d) polysomnographic studies failed to detect
      clinically relevant sleep disturbance in PTSD, although an increase in brief
      arousal from REM was detected. Methodological questions raised by discrepancies
      between biological findings from epidemiologic versus clinical and other
      selective samples are discussed.

PMID- 16891574
TI  - Social context and the psychobiology of posttraumatic stress.
AB  - A growing body of research is identifying the molecular and genetic correlates of
      psychopathology and holds tremendous promise in suggesting the biologic
      mechanisms that may explain emergent posttraumatic stress disorder (PTSD)
      phenotypes. Another body of research has begun to consider how elements of the
      social context may influence the risk of PTSD. It is likely that the social
      context and molecular/genetic factors jointly determine the risk of PTSD and as
      such scientific inquiry that considers the interrelationship of these factors
      stands to advance the field. However, there are particular conceptual and
      methodologic challenges to conducting and designing studies that adequately
      assess both the social context and the biologic determinants of PTSD. Much of the
      current research exploring the biology of PTSD is conducted with highly selective
      samples that were recruited on the basis of strict phenotypic or medical history
      criteria. In contrast, population-based sampling represents an opportunity to
      obtain heterogeneous samples that better represent the population distribution of
      relevant molecular, genotypic, and phenotypic parameters of interest. These
      sampling strategies also allow researchers to consider the role of the social
      context and in turn, how the social context influences the molecular determinants
      of PTSD. An example of our own work illustrates the feasibility of the population
      based sampling approach.

PMID- 16891576
TI  - Developmental epidemiology of PTSD: self-regulation as a central mechanism.
AB  - Epidemiologic and meta-analytic studies point to consistent effects of pretrauma
      factors on risk for posttraumatic stress disorder (PTSD). However, our
      understanding of why only some individuals are vulnerable to the adverse effects
      of traumatic events remains limited. This article argues that a developmentally
      informed approach to the epidemiology of PTSD is needed to move this
      understanding forward. However, there are many challenges to such an approach
      including the historic conceptualization of PTSD as a normative response to
      traumatic events, the almost exclusive reliance on retrospective self-report of
      PTSD risk factors, and the lack of attention to current knowledge of human
      development in selecting risk factors for epidemiologic studies. The
      developmental construct of self-regulation may provide a key mechanism for
      understanding the effects of pretrauma factors on the vulnerability to PTSD.
      Pretrauma factors shown to have consistent effect on risk for PTSD in meta
      analytic studies include familial psychopathology, child abuse, and preexisting
      psychopathology. A preliminary framework integrating these pretrauma factors with
      self-regulation as a central mechanism in the etiology of PTSD is presented. The
      implications of a developmentally informed epidemiologic approach to PTSD for
      theory, research, and practice are discussed.

PMID- 16891575
TI  - Clarifying the origin of biological abnormalities in PTSD through the study of
      identical twins discordant for combat exposure.
AB  - A biological abnormality found to be associated with posttraumatic stress
      disorder (PTSD) may be, among other things, a pretrauma vulnerability factor,
      that is, it may have been present prior to the event's occurrence and increased
      the individual's likelihood of developing PTSD upon traumatic exposure.
      Alternately, it may be an acquired PTSD sign, that is, it may have developed
      after the traumatic exposure, along with the PTSD. We have studied pairs of
      Vietnam combat veterans and their noncombat-exposed, identical twins in an effort
      to resolve these competing origins. Combat veterans were diagnosed as current
      PTSD or non-PTSD (i.e., never had). Average heart rate responses (HRRs) to a
      series of sudden, loud-tone presentations were larger in Vietnam combat veteran
      twins with PTSD, but these larger responses were not shared by their noncombat
      exposed cotwins, whose responses were similar to those of the non-PTSD combat
      veterans and their noncombat-exposed cotwins. These results suggest that larger
      HRRs to sudden, loud tones represent an acquired sign of PTSD. In contrast,
      increased neurological soft signs (NSSs), diminished hippocampal volume, and
      presence of abnormal cavum septum pellucidum (CSP) were found in Vietnam combat
      veteran twins with PTSD and their "high-risk," unexposed cotwins compared to
      Vietnam combat veteran twins without PTSD and their "low-risk," unexposed
      cotwins. These results support the conclusion that the latter abnormalities
      represent antecedent, familial vulnerability factors for developing chronic PTSD
      upon exposure to a traumatic event.

PMID- 16891577
TI  - Applying biological data in the forensic and policy arenas.
AB  - Of the biological measures in the field of traumatic stress studies, the script
      driven imagery paradigm has yielded the most consistent data. Approximately, two
      thirds of individuals with a diagnosis of posttraumatic stress disorder (PTSD)
      exhibit heightened psychophysiologic reactivity while listening to audiotaped
      descriptions of their traumatic autobiographical memories. Nevertheless, these
      findings do not necessarily indicate the presence of PTSD or even that the
      memories are genuine. For example, people reporting (presumably) false memories
      of having been abducted by space aliens similarly exhibit heightened reactivity,
      even though they do not suffer from PTSD. To enhance the validity of diagnostic
      decision making in the forensic and policy arenas, we can use the methods of
      historians, specifically, consulting archival records to verify trauma histories
      and supplement biological data.

PMID- 16891578
TI  - Clinical implications of neuroscience research in PTSD.
AB  - The research showing how exposure to extreme stress affects brain function is
      making important contributions to understanding the nature of traumatic stress.
      This includes the notion that traumatized individuals are vulnerable to react to
      sensory information with subcortically initiated responses that are irrelevant,
      and often harmful, in the present. Reminders of traumatic experiences activate
      brain regions that support intense emotions, and decrease activation in the
      central nervous system (CNS) regions involved in (a) the integration of sensory
      input with motor output, (b) the modulation of physiological arousal, and (c) the
      capacity to communicate experience in words. Failures of attention and memory in
      posttraumatic stress disorder (PTSD) interfere with the capacity to engage in the
      present: traumatized individuals "lose their way in the world." This article
      discusses the implications of this research by suggesting that effective
      treatment needs to involve (a) learning to tolerate feelings and sensations by
      increasing the capacity for interoception, (b) learning to modulate arousal, and
      (c) learning that after confrontation with physical helplessness it is essential
      to engage in taking effective action.

PMID- 16891579
TI  - Establishing an agenda for translational research on PTSD.
AB  - Animal research on brain mechanisms involved in psychiatric disorders presents an
      enormous challenge because it is impossible to precisely model symptoms of a
      human disorder in a rat or mouse. Nevertheless, there are uses for animal models
      as long as the limitations are recognized. Animal research related to
      posttraumatic stress disorder (PTSD) points to acute and chronic stressors, such
      as restraint or immobilization as being the most relevant stimuli to study how
      neural and endocrine systems are affected, both immediately and long term. Of
      particular relevance are the onset and duration of effects of stressors on brain
      areas subserving emotional memories, such as the amygdala, prefrontal cortex, and
      hippocampus. The hippocampus plays a role in memory and in vegetative functions
      of the body. The hippocampus receives input from the amygdala and its function in
      spatial memory is altered by amygdala activity. Repeated stress in the rat
      suppresses dentate gyrus neurogenesis and causes dendrites of hippocampal and
      medial prefrontal cortical neurons to shrink. Conversely, it causes basolateral
      amygdala neurons to increase in dendritic complexity and sprout new synapses.
      Repeated stress also increases fear and aggression, reduces spatial memory, and
      alters contextual fear conditioning. Antidepressants and mood stabilizers have
      diverse effects on these processes. New data indicate that a single stress
      episode can cause a delayed alteration in synapse formation in the basolateral
      amygdala without changing dendritic length and branching. Further studies are
      examining the structural changes in prefrontal cortex and hippocampus as a result
      of single traumatic stressors, which may reflect the functional interactions with
      the amygdala. Together with mechanistic studies of the role of adrenal
      glucocorticoids and catecholamines, these results may tell us how the brain is
      shaped by acute and repeated uncontrollable stress in ways that then can be
      investigated in human anxiety disorders.

PMID- 16891580
TI  - Neurobiological consequences of early stress and childhood maltreatment: are
      results from human and animal studies comparable?
AB  - Recent studies have reported an association between exposure to childhood abuse
      or neglect and alterations in brain structure or function. One limitation of
      these studies is that they are correlational and do not provide evidence of a
      cause-effect relationship. Preclinical studies on the effects of exposure to
      early life stress can demonstrate causality, and can enrich our understanding of
      the clinical research if we hypothesize that the consequences of early abuse are
      predominantly mediated through the induction of stress responses. Exposure to
      early abuse and early stress has each been associated with the emergence of
      epileptiform electroencephalogram (EEG) abnormalities, alterations in corpus
      callosum area, and reduced volume or synaptic density of the hippocampus.
      Further, there is evidence that different brain regions have unique periods when
      they are maximally sensitive to the effects of early stress. To date, preclinical
      studies have guided clinical investigations and will continue to provide
      important insight into studies on molecular mechanisms and gene-environment
      interactions.

PMID- 16891581
TI  - Toward an animal model of posttraumatic stress disorder.
AB  - Posttraumatic stress disorder (PTSD) belongs to the most frequent anxiety
      disorders. Despite a broad body of evidence concerning neurobiological correlates
      of this illness, the pathomechanisms of PTSD are still poorly understood. This
      illustrates the need to establish animal models of this disorder. Recently, PTSD
      model has become a somewhat fashionable term used in animal studies for almost
      every stress-induced behavioral alteration. Only few cases, however, reflect the
      human disorder closely enough to deserve this term. Systematic research requires
      valid animal modeling with clearly defined criteria. This article outlines and
      discusses criteria for prospective PTSD models, based on a theoretical framework
      that emphasizes the involvement of both associative and nonassociative memory
      processes in the development and maintenance of PTSD.

PMID- 16891582
TI  - The contribution of an animal model toward uncovering biological risk factors for
      PTSD.
AB  - Clinical studies of posttraumatic stress disorder (PTSD) have elicited proposed
      risk factors for developing PTSD in the aftermath of stress exposure. Generally,
      these risk factors have arisen from retrospective analysis of premorbid
      characteristics of study populations. A valid animal model of PTSD can complement
      clinical studies and help to elucidate issues, such as the contribution of
      proposed risk factors, in ways which are not practicable in the clinical arena.
      Important qualities of animal models include the possibility to conduct
      controlled prospective studies, easy access to postmortem brains, and the
      availability of genetically manipulated subjects, which can be tailored to
      specific needs. When these qualities are further complemented by an approach
      which defines phenomenologic criteria to address the variance in individual
      response pattern and magnitude, enabling the animal subjects to be classified
      into definable groups for focused study, the model acquires added validity. This
      article presents an overview of a series of studies in such an animal model which
      examine the contribution of two proposed risk factors and the value of two early
      postexposure pharmacological manipulations on the prevalence rates of subjects
      displaying an extreme magnitude of behavioral response to a predator stress
      paradigm.

PMID- 16891583
TI  - Glucocorticoid "programming" and PTSD risk.
AB  - Epidemiological data have linked an adverse fetal environment with increased
      risks of cardiovascular, metabolic, neuroendocrine, and psychiatric disorders in
      adulthood. Prenatal stress and/or glucocorticoid excess might underlie this link.
      In animal models, prenatal stress, glucocorticoid exposure or inhibition/knockout
      of 11 beta-hydroxysteroid dehydrogenase type 2 (11 beta-HSD-2), the feto
      placental barrier to maternal glucocorticoids, reduces birth weight and causes
      permanent hypertension, hyperglycemia, increased hypothalamic-pituitary-adrenal
      (HPA) axis activity and behavior resembling of anxiety. In humans, 11 beta-HSD-2
      gene mutations cause low birth weight and placental 11 beta-HSD-2 activity
      correlates directly with birth weight and inversely with infant blood pressure.
      Low birth weight babies have higher plasma cortisol levels throughout adult life,
      indicating HPA programming. In human pregnancy, severe maternal stress affects
      the offspring HPA axis and associates with neuropsychiatric disorders.
      Posttraumatic stress disorder (PTSD) appears to be a variable in the effects.
      Intriguingly, some of these effects appear to be 'inherited' into a further
      generation, itself unexposed to exogenous glucocorticoids at any point in the
      lifespan from fertilization, implying epigenetic marks persist into subsequent
      generation(s). Overall, the data suggest that prenatal exposure to excess
      glucocorticoids programs peripheral and CNS functions in adult life, predisposing
      to some pathologies, perhaps protecting from others, and these may be transmitted
      perhaps to one or two subsequent generations.

PMID- 16891584
TI  - Developing an agenda for translational studies of resilience and vulnerability
      following trauma exposure.
AB  - Here we outline a translational research agenda for studies of resilience,
      defined as the process of adapting well in the face of adversity or trauma. We
      argue that an individual differences approach to the study of resilience, in
      which the full range of behavioral and biological responses to stress exposure is
      examined can be applied across human samples (e.g., people who have developed
      psychopathology versus those who have not; people who have been exposed to trauma
      versus those who have not) and even, in some cases, across species. We delineate
      important psychological resilience-related factors including positive affectivity
      and optimism, cognitive flexibility, coping, social support, emotion regulation,
      and mastery. Key brain regions associated with stress-related psychopathology
      have been identified with animal models of fear (e.g., extinction and fear
      conditioning; memory reconsolidation) and we describe how these regions can be
      studied in humans using neuroimaging technology. Finally, we cite recent research
      identifying neuroendocrine markers of resilience and recovery in humans (e.g.,
      neuropeptide Y [NPY], dehydroepiandrosterone [DHEA]) that can also be measured,
      in some cases, in other species. That exposure to adversity or trauma does not
      necessarily lead to impairment and the development of psychopathology in all
      people is an important observation. Understanding why this is so will provide
      clues for the development of therapeutic interventions for those people who do
      develop stress-related psychopathology, or even for the prevention of adverse
      outcomes.

PMID- 16891585
TI  - Alexithymia in PTSD: psychometric and FMRI studies.
AB  - Two studies examined correlates of alexithymia in posttraumatic stress disorder
      (PTSD). In study 1 (n = 77 individuals with PTSD and 45 controls) Toronto
      alexithymia scale (TAS-20) scores were positively correlated with PTSD symptoms,
      dissociation, and childhood abuse and neglect. In study 2, TAS-20 scores were
      examined as correlates of functional magnetic resonance imaging (fMRI) blood
      oxygen level dependent (BOLD) response to trauma script imagery. In 16 controls,
      TAS-20 scores correlated positively with response in medial prefrontal cortex
      (mPFC), and negatively with response in anterior cingulate cortex (ACC) and
      thalamus. In 26 individuals with PTSD, TAS-20 scores correlated positively with
      response in insula, posterior cingulate cortex (PCC), and thalamus, and
      negatively with response in ACC.

PMID- 16891586
TI  - Neuroimaging of pain perception in Dutch veterans with and without posttraumatic
      stress disorder: preliminary results.
AB  - This article presents initial data on the application of a pain protocol in
      posttraumatic stress disorder (PTSD) to assess the neural circuitry that is
      involved in the disorder, with a special interest in the role of the anterior
      cingulate cortex (ACC). Preliminary analysis demonstrated a specific and
      differentiated role for the ACC. Fixed affects analysis demonstrated that stimuli
      subjectively perceived as more painful resulted in increased activation of the
      caudal ACC, whereas less painful stimuli resulted in increased activation of the
      rostral ACC in both groups.

PMID- 16891587
TI  - The relationship between hippocampal volume and declarative memory in a
      population of combat veterans with and without PTSD.
AB  - Both reduced hippocampal volume and cognitive alterations have been found in
      posttraumatic stress disorder (PTSD). The purpose of this article was to examine
      the relationship between hippocampal volume, combat exposure, symptom severity,
      and memory performance in a sample of combat veterans with and without a history
      of PTSD. Subjects were 33 male veteran volunteers (16 PTSD+, 17 PTSD-) who
      underwent an MRI and neuropsychological testing with the California Verbal
      Learning Test (CVLT), a measure of declarative memory. Relationships between
      hippocampal volume (i.e., right + left hippocampal volume/whole brain volume) and
      performance on the CVLT were determined using partial correlational analysis
      controlled for age and Wechsler Adult Intelligence Scale, Third Edition (WAIS
      III) vocabulary scores. Percent hippocampal volume for the entire sample was
      positively associated with several aspects of memory performance as reflected by
      the CVLT. In the PTSD+ group, CVLT performance was negatively correlated with
      lifetime, but not current CAPS symptoms. CVLT performance appears to be strongly
      correlated with hippocampal volume in a group of trauma survivors with and
      without PTSD. Insofar as CVLT performance in the PTSD group was negatively
      associated with worst episode, but not to current PTSD symptoms, memory
      performance in combat veterans may reflect some aspect of risk related to the
      magnitude of the psychological response to trauma, rather than current symptoms
      that may be interfering with cognitive performance. It will be of interest to
      study cognitive abilities that may relate to the likelihood of specific PTSD
      symptoms and to track changes in CVLT performance and hippocampal volume over
      time in persons with and without a history of trauma exposure.

PMID- 16891589
TI  - Moderators of PTSD-related psychophysiological effect sizes: results from a meta
      analysis.
AB  - Though many studies have reported psychophysiological differences between
      individuals with and without posttraumatic stress disorder (PTSD), there have
      been inconsistencies in the magnitude of observed effect sizes across studies.
      Following a meta-analysis of the effect of current PTSD on psychophysiology
      during resting baseline, startle, standard trauma cue, and idiographic trauma cue
      studies, the author examined moderators of the obtained effect sizes. Results
      revealed that, among several moderators examined, greater PTSD effects on
      psychophysiology were most consistently associated with trauma-free control
      groups, greater PTSD symptom severity, and studies using earlier rather than more
      recent diagnostic criteria for PTSD (e.g., DSM-III versus DSM-IV).

PMID- 16891588
TI  - Cognitive effects of intravenous hydrocortisone in subjects with PTSD and healthy
      control subjects.
AB  - On the basis of peripheral (nonbrain) neuroendocrine findings in subjects with
      posttraumatic stress disorder (PTSD), it has been hypothesized that these
      individuals also have a greater central (brain) sensitivity to glucocorticoids.
      In nonpsychiatric subjects, it has been found that working and declarative memory
      performance is selectively impaired by acute glucocorticoid administration. We
      hypothesized that subjects with PTSD, as compared to nonpsychiatric controls,
      would show greater impairments in verbal declarative memory and working memory,
      but not attention, following exogenous glucocorticoid administration. These data
      are part of a larger study using functional neuroimaging and peripheral HPA axis
      measures in these same subjects. Subjects underwent a 0.5-mg dexamethasone
      suppression test and measurement of basal cortisol, basal plasma lymphocyte
      glucocorticoid receptor number, and postdexamethasone cortisol on a separate day.
      Under double-blind randomized crossover conditions, 17-mg hydrocortisone or
      placebo was administered by intravenous (i.v.) bolus to 15 medication-free PTSD
      subjects (4 female) and 12 nonpsychiatric control subjects (4 female) matched by
      age, sex, and education level. Participants then underwent positron emission
      tomography (PET) scanning and 90 min after the initial drug/placebo
      administration, cognitive testing was then performed. By repeated measures ANCOVA
      (covaried for baseline performance on that neuropsychological test), neither
      attention tasks of digit span forward nor backward showed significant change.
      However, there were significant drug (F = 17.644, df = 1,25 P < 0.001), group (F
      = 4.383, df = 1,25 P = 0.048), and drug by group interactions (F = 4.756, df =
      1,25 P = 0.040) for verbal declarative memory. By t-test, there was not a
      difference in baseline performance on this measure between subject groups. The
      subject group with PTSD experienced a greater decline in verbal declarative
      memory performance following hydrocortisone administration. For working memory,
      there were significant group (F = 6.048, df = 1,25 P = 0.022) and drug by group
      interactions (F = 6.048, df = 1,25 P = 0.022) for verbal declarative memory. By t
      test, there was not a difference in baseline performance on this measure between
      subject groups. The hydrocortisone administration led to impairment in working
      memory in the group of subjects with PTSD, but not in the control subject group.
      Exploratory correlations between percent cortisol suppression following
      dexamethasone and baseline plasma lymphocyte glucocorticoid receptor number with
      declarative and working memory measures among subject groups separately and in a
      combined way revealed a negative correlation between lymphocyte glucocorticoid
      receptor density and working memory (r = -0.54, df = 25, P = 0.008). Brain
      sensitivity to glucocorticoids appears to be greater in subjects with PTSD.
      Heightened vulnerability of declarative memory in subjects with PTSD may indicate
      hippocampal involvement, whereas working memory vulnerability suggests additional
      brain regions (prefrontal, cingulate, temporal, and parietal cortices) and
      neurotransmitter systems (dopamine and serotonin) particularly sensitive to
      glucocorticoids in persons with PTSD.

PMID- 16891590
TI  - Association between alexithymia and neuroendocrine response to psychological
      stress in police academy recruits.
AB  - Alexithymia has been associated with both posttraumatic stress disorder and
      neuroendocrine responses to stress. This study examined the relationship of
      alexithymia to salivary cortisol and 3-methoxy-4-hydroxy-phenylglycol (MHPG) in a
      sample of police academy recruits exposed to a video stress challenge.
      Alexithymia scores were negatively associated with catecholamine response to the
      video challenge but no association was found between alexithymia scores and
      cortisol reactivity.

PMID- 16891591
TI  - Increased cortisol in women with intimate partner violence-related posttraumatic
      stress disorder.
AB  - Intimate partner violence (IPV) is a chronic and recurrent traumatic stressor
      associated with PTSD; however, its biological correlates are not well understood.
      This study examined diurnal salivary cortisol and platelet catecholamines in
      women with lifetime IPV-related PTSD and in women exposed to IPV who did not
      develop PTSD. Cortisol was elevated in women with lifetime PTSD compared to
      controls. No differences were found for platelet catecholamines.

PMID- 16891592
TI  - Differential effects of subtypes of trauma symptoms on couples' hypothalamus
      pituitary-adrenal (HPA) axis reactivity and recovery in response to interpersonal
      stress.
AB  - This article examined the relation of five subtypes of trauma symptoms to
      hypothalamus-pituitary-adrenal (HPA) functioning as assessed with salivary
      cortisol before, during, and after an experimentally induced interpersonal
      conflict task in 194 heterosexual young adult couples. Trauma history and
      symptoms were assessed through structured clinical interviews and standardized
      self-report measures. Hierarchical linear modeling was used to analyze the
      effects of trauma symptoms on trajectories of cortisol reactivity to and recovery
      from the interpersonal stress. Trauma-related anxiety, depression, sleep
      disturbances, and dissociation significantly predicted cortisol reactivity and
      recovery. Trauma-related anxiety, sleep disturbances, and sexual problems
      significantly predicted partners' cortisol reactivity to interpersonal stress.

PMID- 16891593
TI  - Effect of high-dose cortisol on memory functions.
AB  - Although research indicates that hightened glucocorticoid levels impair long-term
      memory functions and may inhibit traumatic memory retrieval in humans, the impact
      of acutely elevated glucocorticoid levels on learning and attentional functions
      is still unclear. Furthermore, the effect of glucocorticoids on executive
      functions as well as the recovery from long-term memory deficits is
      insufficiently studied. The present study examined memory functions in patients
      with acute exacerbation of neurological diseases (multiple sclerosis, acute optic
      neuritis), who were treated with a high dose of glucocorticoids. All patients
      demonstrated a reversible impairment of long-term memory functions, whereas
      measures of short-term memory, attentional functions, and alertness remained
      unaffected. These findings indicate a selective cognitive disturbance, providing
      further evidence that the memory deficits reflect a receptor-mediated effect of
      glucocorticoids on hippocampal function thereby supporting a potential
      association of stress-induced elevated cortisol levels and memory disturbances in
      trauma-related psychiatric disorders (psychogenic amnesia, PTSD).

PMID- 16891594
TI  - Ecological study of sleep disruption in PTSD: a pilot study.
AB  - Laboratory-based sleep studies have yielded inconsistent results regarding the
      presence and nature of objective sleep anomalies in posttraumatic stress disorder
      (PTSD). This pilot study aimed at assessing sleep in adult crime victims with
      PTSD by using in-home polysomnography. Compared to healthy archival subjects,
      PTSD subjects showed longer sleep latency, reduced total sleep time, and
      increased duration of nocturnal awakening. Quantitative electroencephalography
      (EEG) measures of delta and beta activity also differed in PTSD and healthy
      subjects. These preliminary findings suggest that ambulatory methods can capture
      objective signs of sleep disruption, and corroborate subjective complaints of
      disrupted sleep in PTSD.

PMID- 16891595
TI  - Allostatic load in women with and without PTSD symptoms.
AB  - Allostatic load (AL) is the cumulative physiological "cost" of prolonged stress.
      An AL composite measure successfully predicts morbidity and mortality among the
      elderly but has not been reported in "high stress" samples with posttraumatic
      stress disorder (PTSD). Accordingly, AL was measured in mothers (ages 29-55) of
      pediatric cancer survivors and control mothers of healthy children. A significant
      "dose-response" pattern (high to low AL) emerged: cancer mothers meeting all PTSD
      criteria, cancer mothers with no/low symptoms, and controls, respectively.
      Results indicate elevated AL can be detected in relatively young women with high
      stress histories, and particularly those with PTSD.

PMID- 16891596
TI  - The ACTH response to dexamethasone in Persian Gulf War veterans.
AB  - The basis of postdeployment health symptoms in Gulf War veterans remains poorly
      understood. Alterations in the feedback regulation of the hypothalamic-pituitary
      adrenal (HPA) axis have been demonstrated in posttraumatic stress disorder (PTSD)
      and other bodily disorders related to stress. The objective of this article was
      to examine whether similar HPA axis alterations are related to Gulf War
      deployment, postdeployment health symptoms, or PTSD. Plasma adrenocorticotropic
      hormone (ACTH) was measured on consecutive mornings at 08:00 h before and after a
      low dose of oral dexamethasone (DEX) at 23:00 h in Gulf War veterans with PTSD (n
      = 14), Gulf War veterans without PTSD (n = 11), and healthy veterans never
      deployed to a war zone (n = 12). Both Gulf War veterans with PTSD and Gulf War
      veterans without PTSD had significantly lower post-DEX ACTH levels than the
      nonexposed veterans, in the absence of group differences in basal ACTH or DEX
      levels. Among Gulf War veterans, post-DEX ACTH levels were significantly
      associated with musculoskeletal symptoms. Gulf War deployment and postdeployment
      health symptoms appear to be associated with alterations in feedback regulation
      of the pituitary gland that suggests a possible common link between
      postdeployment health symptoms and other chronic stress-related conditions.

PMID- 16891597
TI  - The effect of maternal PTSD following in utero trauma exposure on behavior and
      temperament in the 9-month-old infant.
AB  - In view of evidence of in utero glucocorticoid programming, and our prior
      observation of lower cortisol levels in 9-month-old infants of mothers with
      posttraumatic stress disorder (PTSD) compared to mothers without PTSD, we
      undertook an examination of the effect of in utero maternal stress, as determined
      by PTSD symptom severity, and maternal cortisol levels on behavioral outcomes in
      the infant. METHODS: Ninety-eight pregnant women directly exposed to the World
      Trade Center (WTC) collapse on 9/11 provided salivary cortisol samples and
      completed a PTSD symptom questionnaire and a behavior rating scale to measure
      infant temperament, including distress to limitations, and response to novelty.
      RESULTS: Mothers who developed PTSD in response to 9/11 had lower morning and
      evening salivary cortisol levels, compared to mothers who did not develop PTSD.
      Maternal morning cortisol levels were inversely related to their rating of infant
      distress and response to novelty (i.e., loud noises, new foods, unfamiliar
      people). Also, mothers who had PTSD rated their infants as having greater
      distress to novelty than did mothers without PTSD (t = 2.77, df = 61, P = 0.007).
      CONCLUSION: Longitudinal studies are needed to determine how the association
      between maternal PTSD symptoms and cortisol levels and infant temperament reflect
      genetic and/or epigenetic mechanisms of intergenerational transmission.

PMID- 16891598
TI  - Longitudinal assessment of dissociation in Holocaust survivors with and without
      PTSD and nonexposed aged Jewish adults.
AB  - The trajectory of posttraumatic stress disorder (PTSD) and PTSD-related symptoms
      in relation to aging is not well understood. We previously observed higher levels
      of dissociation as measured by the Dissociative Experiences Scale (DES) among
      older Holocaust survivors with, compared to those without, PTSD, though scores on
      the DES in Holocaust survivors were markedly lower than those that had been
      reported for younger cohorts. We undertook a longitudinal evaluation of
      dissociation in Holocaust survivors. Twenty-six Holocaust survivors with current
      PTSD, 30 Holocaust survivors without current PTSD, and 19 nonexposed were
      evaluated at the initial evaluation and subsequently 8.11 years later. Repeated
      measures analysis of variance (ANOVA) on the DES scores from these times
      demonstrated a significant main effect for time and a significant group by time
      interaction, reflecting a marked decline in Holocaust survivors, particularly
      those with PTSD. Controlling for age obliterated the effect of time, but not the
      group by time interaction. A similar pattern was shown with The Clinician
      Administered PTSD Scale (CAPS) scores. Different symptoms related to PTSD show
      different trajectories of change with age, with dissociation appearing to be less
      prominent with age.

PMID- 16891599
TI  - World War II never ended in my house: interviews of 12 Office of Strategic
      Services veterans of wartime espionage on the 50th anniversary of WW II.
AB  - The author conducted sociological interviews of 12 OSS spies (7 male, 5 female)
      who were operatives in France during World War II (WW II). The Office of
      Strategic Services (OSS) existed from 1941 to 1945 and was later renamed the CIA
      in 1947. This paper includes family studies of six close relatives of OSS vets
      and observation of 400 OSS veterans at the 50th anniversary of WW II. Three of
      the 12 OSS veterans who had been tortured by the Gestapo still suffered from PTSD
      startle symptoms after 50 years; those three also suffered massive strokes in
      later life. The majority of OSS vets, regardless of gender, exhibited "war
      excitement" when talking about the war 50 years later. Most saw the war as the
      highpoint of their lives. War excitement needs more careful study within PTSD
      circles.

PMID- 16891600
TI  - Assessment of posttraumatic stress symptoms in children who are medically ill and
      children presenting to a child trauma program.
AB  - To test the utility of the UCLA posttraumatic stress disorder (PTSD) Index for
      DSM-IV (U-PTSD-I)(c) for predicting PTSD diagnosis in children with and without
      medical illnesses. The U-PTSD-I and a standard psychiatric interview were
      administered to medically ill children (n = 76) and children who experienced
      other traumatic events (n = 31). We found U-PTSD-I's sensitivity and specificity
      was better in the nonmedical illness cohort. Only intrusion symptoms were
      significantly associated with the diagnosis of PTSD in the medically ill. In
      conclusion, the U-PTSD-I performs better among general trauma versus medically
      ill patients. Intrusion symptoms should be focused on when assessing PTSD in
      medically ill children.

PMID- 16891601
TI  - Medical screenings as a trigger for PTSD in Public Safety Workers.
AB  - Emotional distress appears to be a component of the medical screening process for
      9/11 Public Safety Workers. A significant number of Public Safety Workers have
      found the anticipation of the medical examination process and actual examination
      to trigger reexperiencing and problems of emotional regulation. Selective Case
      examples are presented to illustrate how Public Safety Workers might be better
      prepared for this process.

PMID- 16891602
TI  - Bio-psycho-social assessment of 9/11-bereaved children.
AB  - A comprehensive and integrated assessment bio-psycho-social model for the
      assessment of children who lost parents in the World Trade Center is necessary so
      that effective short-term and long-term care planning can be achieved. This model
      has been used to guide assessments of children in the Care Alliance project.
      Rationale for this model, as well as preliminary findings from the Care Alliance
      project are presented.

PMID- 16891603
TI  - Are adult offspring reliable informants about parental PTSD? A validation study.
AB  - We developed a short questionnaire--Parental PTSD Questionnaire--(PPQ), designed
      to assess the presence of posttraumatic stress disorder (PTSD) symptoms in
      parents. Fifty-eight adult offspring of Holocaust survivors (23 men and 35 women)
      completed the questionnaire about a parent who was independently evaluated by a
      trained clinician using the Clinician Administered PTSD Scale (CAPS). Only 5.2%
      of the offspring reported, "not knowing" if their parent had experienced 10 or
      fewer symptoms, while 56.9% provided estimates for all 17 items. There were no
      significant differences between lifetime frequencies of the individual symptoms
      as endorsed on the PPQ compared to the CAPS when subjects with completed PPQs
      were compared with CAPS. Interrater reliability between offspring and clinician
      was highly significant for each of the items when evaluated separately so as to
      include data for subjects who endorsed not knowing if a certain symptom had been
      present. Further studies are warranted to examine the psychometric properties of
      this measure.

PMID- 16891604
TI  - Posttraumatic stress disorder with amnesia following asphyxiation.
AB  - We describe five cases of traumatic asphyxiation injury, each meeting diagnostic
      criteria for posttraumatic stress disorder (PTSD) and characterized by a range of
      postinjury cognitive impairment. Four patients exhibited dense retrograde
      amnesia, including absence of conscious memory for the traumatic event.
      Appreciation of these asphyxiation cases, which involve temporally extended
      trauma exposure, may help resolve arguments regarding the possibility of co
      occurrence of PTSD and neurological amnesia based exclusively on observations of
      much briefer duration events (specifically, motor vehicle crashes). These five
      cases also provide evidence that cognitive symptoms of PTSD can develop in the
      absence of conscious memory for the event.

PMID- 16891605
TI  - Women and reproductive-related trauma.
AB  - Women are at higher risk for developing posttraumatic stress disorder (PTSD) than
      men, leading to significant psychosocial burden and healthcare-related costs.
      Research has shown an association between the negative impact of traumatic
      experiences and the reproductive life cycle in women. Pregnant women with a
      history of abuse/trauma frequently report intrusive reemergence of symptoms.
      Women who experience miscarriage may present with even higher prevalence rates of
      PTSD symptoms. Both psychologic and physiologic factors are believed to be
      relevant to the development of peripartum posttraumatic stress symptoms. Much
      less is known, however, about treatment. A case series of patients who presented
      with PTSD symptoms in the context of reproductive-related traumatic events (e.g.,
      miscarriage, stillbirth) or who experienced reemergence of symptoms during
      pregnancy is presented, including treatment strategies.

PMID- 16891606
TI  - Posttraumatic stress disorder and other psychological sequelae among world trade
      center clean up and recovery workers.
AB  - We assessed the health of workers exposed to the World Trade Center (WTC) site
      and of a comparison group of unexposed workers, by means of a mail survey.
      Exposed workers reported higher frequency of symptoms consistent with
      posttraumatic stress disorder (PTSD), depression, anxiety, and other
      psychological problems, approximately 20 months after the disaster. PTSD was
      positively associated with traumatic on-site experiences and with respiratory
      problems. These findings may have important clinical and public health
      implications.

PMID- 16891607
TI  - The application of virtual reality to the treatment of PTSD following the WTC
      attack.
AB  - Recent research suggests that virtual reality (VR) enhanced exposure therapy may
      enhance the efficacy of treatment through increasing patient engagement in the
      exposure. This study evaluated the use of VR in the treatment of PTSD following
      the WTC attack of September 11, 2001. Individuals in a 14 session VR-enhanced
      treatment (n=9) were compared to a waitlist (WL) control group (n=8). ANOVA
      showed a significant interaction of time by group (p<.01) with a large effect
      size of 1.53. The VR group showed significantly greater post-treatment decline in
      CAPS scores compared to the WL. Our preliminary data suggests that VR is an
      effective tool for enhancing exposure therapy for both civilians and disaster
      workers who suffer from PTSD.

PMID- 16891608
TI  - Pharmacotherapeutic treatment of nightmares and insomnia in posttraumatic stress
      disorder: an overview of the literature.
AB  - Sleep disturbances are hallmark symptoms of posttraumatic stress disorder (PTSD).
      Where the subjective experience of nightmares and insomnia in PTSD patients is
      very real indeed and demands treatment, objective research findings on disordered
      sleep architecture in PTSD are inconclusive and inconsistent. After reviewing the
      literature an insufficient number of controlled studies are published to
      formulate evidence-based guidelines. Several studies have methodological
      limitations, such as small group sizes and heterogenic samples. Large randomized
      controlled trials (RCTs) need to be conducted in order to further develop
      adequate therapeutic interventions. Objective parameters for insomnia and
      nightmares need to be identified for understanding underlying mechanisms of
      disturbed sleep in PTSD, and for evaluating therapy.

PMID- 16891609
TI  - Treatment of PTSD by eye movement desensitization reprocessing (EMDR) improves
      sleep quality, quality of life, and perception of stress.
AB  - The impact of posttraumatic stress disorder (PTSD) on the sleep of patients is
      widely reported. However, the parameters that can be altered are not the same for
      all patients. Some studies report an impairment of sleep maintenance and
      recurrent nightmares, while others failed to find such alterations. Among the
      many treatments, the eye movement desensitization reprocessing (EMDR) is a
      therapy used specifically to treat PTSD and general trauma. The purpose of this
      study was to examine whether EMDR treatment can improve PTSD symptoms, such as
      sleep, depression, anxiety, and poor quality of life.

PMID- 16891610
TI  - Clinical correlates of 24-h cortisol and norepinephrine excretion among subjects
      seeking treatment following the world trade center attacks on 9/11.
AB  - Whereas trauma-associated arousal has been linked fairly consistently with
      elevations in both glucocorticoids and catecholamines, neuroendocrine correlates
      of hyperarousal in the context of posttraumatic stress disorder (PTSD) have been
      more variable. Further, neuroendocrine predictors of the development of PTSD
      following trauma have been related to prior exposure, and data from several
      laboratories suggests that hyperarousal may develop in a neuroendocrine milieu of
      relatively diminished basal glucocorticoid secretion. METHODS: In this article we
      examined 24-h cortisol and norepinephrine excretion in 42 treatment-seeking
      survivors of the 9/11 World Trade Center (WTC) attacks, 32 of whom met criteria
      for PTSD, and 15 of whom met criteria for major depression, at the time of
      evaluation; 14 of the 15 subjects meeting criteria for major depression also
      suffered from PTSD. RESULTS: PTSD subjects' 24-h cortisol excretion (46.3 +/-
      20.0 microL/dL) was lower than that of the non-PTSD cohort (72.2 +/- 22.4
      microL/dL; t = 3.18, df = 37, P = 0.003), and 24-h urinary cortisol was
      negatively correlated with the experience of the WTC attacks as a Criterion-A
      event (r = -0.427, P = 0.007), and with self-rated avoidance (r = -0.466, P =
      0.003) and total score (r = -0.398, P = 0.012) on the PTSD Symptom Scale (PSS).
      In contrast, 24-h norepinephrine excretion was not associated with the
      development of PTSD or with PTSD-related symptoms, but was negatively correlated
      with days since 9/11 at the time of evaluation (r = -0.393, P = 0.015).
      DISCUSSION: The latter finding suggests a relationship of norepinephrine to a
      dimension of stress-related arousal not captured by the symptom-rating scales
      chosen for this study to reflect symptoms related to PTSD and other
      neuropsychiatric disorders, but instead, of one to that of the sudden
      multidimensional life disruption suffered by the WTC survivors that applied for
      treatment. These data also confirm, in a naturalistic sample, the previously
      observed negative association of urinary cortisol excretion with development of
      PTSD in the aftermath of severe trauma exposure.

PMID- 16891611
TI  - Noradrenergic signaling in the amygdala contributes to the reconsolidation of
      fear memory: treatment implications for PTSD.
AB  - Intrusive memories resulting from an emotional trauma are a defining feature of
      posttraumatic stress disorder (PTSD). Existing studies demonstrate that an
      increase of noradrenergic activity during a life-threatening event contributes to
      strengthening or "overconsolidation" of the memory for trauma. The lateral
      nucleus of the amygdala (LA) is critical for fear learning. Using classical fear
      conditioning in rats, we have recently demonstrated that noradrenergic blockade
      in the LA following reactivation of fear memory by retrieval disrupts memory
      reconsolidation and lastingly impairs fear memory. This suggests that
      noradrenergic blockade may be useful in attenuating traumatic memories, even well
      consolidated old memories, in PTSD.

PMID- 16891612
TI  - Maternal-infant response to variable foraging demand in nonhuman primates:
      effects of timing of stressor on cerebrospinal fluid corticotropin-releasing
      factor and circulating glucocorticoid concentrations.
AB  - The maternal stress response may vary as a function of infant developmental
      phase. Using a median split, 13 bonnet macaque (M. radiata) mother-infant dyads
      were exposed to early initiation of variable foraging demand (VFD), a prolonged
      stressor, whereas 11 dyads were exposed to late VFD onset. Cerebrospinal fluid
      (CSF) and plasma samples were obtained from mothers and infants prior to and
      following VFD. Increases in maternal CSF corticotropin-releasing factor (CRF)
      concentrations were evident in response to late, but not early, VFD. Mothers
      exhibited either increased or decreased cortisol concentrations in response to
      VFD. However, absolute cortisol change was greater in early versus late VFD.
      Timing of the VFD stressor differentially affects maternal neuroendocrine
      response, with potential implications for the offspring's developmental
      trajectory.

PMID- 16891613
TI  - Interleukin-1beta as a mechanism for stress-induced startle suppression in
      females.
AB  - Startle measures were taken 2 h following a systemic injection of interleukin
      1beta (IL-1beta) (3 microg/kg) to intact or ovariectomy (OVX) female rats.
      Changes in startle responsivity (reduced startle magnitude) were evident in
      intact IL-1beta-treated rats, despite no significant effects on startle
      sensitivity (number of elicited startles). No significant changes in startle
      sensitivity or responsivity were evident in IL-1beta-treated OVX rats. These
      results are discussed as a possible mechanism for stress-induced suppression of
      startle responsivity seen in intact female rats.

PMID- 16891614
TI  - Role of the bed nucleus of the stria terminalis (BST) in the expression of
      conditioned fear.
AB  - Male Sprague-Dawley rats were trained and tested in the fear-potentiated startle
      (FPS) paradigm to examine the involvement of the bed nucleus of the stria
      terminalis (BST) in the expression of conditioned fear. Studies were designed to
      (a) detect physiological changes in the BST that might correlate with different
      levels of FPS expression and (b) determine if chemical inactivation of the BST
      with muscimol (1 ng) had any effect on FPS expression. The data suggest that the
      BST plays a role in the expression of conditioned fear and that GABA-mediated
      inhibition at this level may influence the level of this expression.

PMID- 16891615
TI  - Developmental trauma is associated with behavioral hyperarousal, altered HPA axis
      activity, and decreased hippocampal neurotrophin expression in the adult rat.
AB  - Effects of early-life trauma on adult behavioral responses, corticosterone (CORT)
      concentration, and levels of nerve growth factor (NGF), brain-derived neutrophic
      factor (BDNF), and neurotrophin-3 (NT-3) in hippocampus and frontal cortex were
      investigated. Traumatized animals showed an increase in rearing in both the
      elevated plus maze and open field after adult restress, higher basal levels of
      CORT, lower levels of BDNF in dorsal hippocampus, and lower levels of NT-3 in
      dorsal and ventral hippocampus. Trauma-related behavioral hyperarousal and
      altered hypothalamic-pituitary-adrenal (HPA) axis activity may be mediated by
      decreases in hippocampal neurotrophin expression.

PMID- 16891616
TI  - Pituitary adenylate cyclase-activating polypeptide (PACAP) 38 and PACAP4-6 are
      neuroprotective through inhibition of NADPH oxidase: potent regulators of
      microglia-mediated oxidative stress.
AB  - Microglial activation is implicated in the progressive nature of numerous
      neurodegenerative diseases, including Parkinson's disease. Using primary rat
      mesencephalic neuron-glia cultures, we found that pituitary adenylate cyclase
      activating polypeptide (PACAP) 38, PACAP27, and its internal peptide, Gly-Ile-Phe
      (GIF; PACAP4-6), are neuroprotective at 10(-13) M against lipopolysaccharide
      (LPS)-induced dopaminergic (DA) neurotoxicity, as determined by [(3)H]DA uptake
      and the number of tyrosine hydroxylase-immunoreactive neurons. PACAP38 and GIF
      also protected against 1-methyl-4-phenylpyridinium(+)-induced neurotoxicity but
      only in cultures containing microglia. PACAP38 and GIF ameliorated the production
      of microglia-derived reactive oxygen species (ROS), where both LPS- and phorbol
      12-myristate 13-acetate-induced superoxide and intracellular ROS were inhibited.
      The critical role of NADPH oxidase for GIF and PACAP38 neuroprotection against
      LPS-induced DA neurotoxicity was demonstrated using neuron-glia cultures from
      mice deficient in NADPH oxidase (PHOX(-/-)), where PACAP38 and GIF reduced tumor
      necrosis factor alpha production and were neuroprotective only in PHOX(+/+)
      cultures and not in PHOX(-/-) cultures. Pretreatment with PACAP6-38 (3 microM;
      PACAP-specific receptor antagonist) was unable to attenuate PACAP38, PACAP27, or
      GIF (10(-13) M) neuroprotection. PACAP38 and GIF (10(-13) M) failed to induce
      cAMP in neuronglia cultures, supporting that the neuroprotective effect was
      independent of traditional high-affinity PACAP receptors. Pharmacophore analysis
      revealed that GIF shares common chemical properties (hydrogen bond acceptor,
      positive ionizable, and hydrophobic regions) with other subpicomolar-acting
      compounds known to inhibit NADPH oxidase: naloxone, dextromethorphan, and Gly-Gly
      Phe. These results indicate a common high-affinity site of action across numerous
      diverse peptides and compounds, revealing a basic neuropeptide regulatory
      mechanism that inhibits microglia-derived oxidative stress and promotes neuron
      survival.

PMID- 16891617
TI  - Calpain mediates the dioxin-induced activation and down-regulation of the aryl
      hydrocarbon receptor.
AB  - The aryl hydrocarbon receptor (AhR) is a ligand-activated basic-helix-loop-helix
      transcription factor that binds polyaromatic hydrocarbons (PAH), such as 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD), and mediates their toxicity. Binding of PAH
      to AhR in the cytoplasm triggers a poorly defined transformation step of the
      receptor into a nuclear transcription factor. In this study, we show that the
      calcium-dependent cysteine protease calpain plays a major role in the ligand
      induced transformation and signaling of AhR. Fluorescence imaging measurements
      showed that TCDD treatment elevates intracellular calcium, providing the trigger
      for calpain activation, as measured toward t-butoxycarbonyl-Leu-Met
      chloromethylaminocoumarin, a calpain-specific substrate. Inhibition of calpain
      activity by the N-benzyloxycarbonyl-Val-Phe-aldehyde (MDL28170) blocked the TCDD
      induced nuclear translocation of AhR in Hepa1c1c7 mouse hepatoma cell line.
      Treatment of the human metastatic breast carcinoma cell line MT-2 with MDL28170
      and 3-(4-iodophenyl)-2-mercapto-(Z)-2-propenoic acid (PD 150606), two calpain
      selective inhibitors, completely abolished the TCDD-induced transactivation of
      AhR as assessed by transcription of CYP1A1 gene. Previous studies have
      established that after TCDD-induced transactivation, the AhR undergoes a massive
      depletion; we show here that selective calpain inhibitors can block this step,
      which suggests that the ligand-induced down-regulation of the AhR is calpain
      dependent. The data presented support a major role for calpain in the AhR
      transformation, transactivation, and subsequent down-regulation, and provide a
      possible explanation for many of the reported phenomena of ligand-independent
      activation of AhR.

PMID- 16891618
TI  - Activation of primary T lymphocytes results in lysosome development and polarized
      granule exocytosis in CD4+ and CD8+ subsets, whereas expression of lytic
      molecules confers cytotoxicity to CD8+ T cells.
AB  - Lytic granule exocytosis is the major cytotoxic mechanism used by CD8(+)
      cytotoxic lymphocytes. CD8(+) T cells acquire this effector function in the
      process characterized by lysosomal biogenesis, induction of expression of
      cytolytic molecules, and their selective sorting into the lysosomal vesicles.
      However, temporal relation of these differentiation stages during T cell
      activation has not been defined precisely. Also, although CD4(+) T cells
      typically do not express lytic molecules as a consequence of activation, and
      therefore, do not acquire granule exocytosis-mediated lytic function, it is not
      clear whether CD4(+) T cells are able to degranulate. By using in vitro TCR
      stimulation of primary mouse lymphocytes, we found that polyclonally activated
      CD4(+) T cells degranulate upon TCR ligation and polarize enlarged lysosomal
      granules in response to target cell recognition, despite the lack of granule
      exocytosis-mediated cytotoxicity. Upon TCR stimulation, resting CD8(+) T cells
      rapidly express lytic molecules and acquire potent lytic function early in
      activation. Maximal cytolytic potential, however, depends on enlargement of
      lysosomal granules during the subsequent activation stages. Thus, polyclonal TCR
      stimulation of resting T cells results in development of lysosomal granules and
      their release upon TCR engagement in CD4(+) and CD8(+) T cells, but only CD8(+) T
      cells acquire lytic function as a result of induction of expression of lytic
      molecules.

PMID- 16891619
TI  - Matrix metalloproteinase 2 and basement membrane integrity: a unifying mechanism
      for progressive renal injury.
AB  - Chronic kidney disease (CKD) and failure are problems of increasing importance.
      Regardless of the primary etiology, CKD is characterized by tubular atrophy,
      interstitial fibrosis, and glomerulosclerosis. It has been assumed that
      diminished matrix metalloproteinase (MMP) activity is responsible for the
      accumulation of the extracellular matrix (ECM) proteins and collagens that typify
      the fibrotic kidney. Here we demonstrate that transgenic renal proximal tubular
      epithelial expression of a specific enzyme, MMP-2, is sufficient to generate the
      entire spectrum of pathological and functional changes characteristic of human
      CKD. At the earliest point, MMP-2 leads to structural alterations in the tubular
      basement membrane, a process that triggers tubular epithelial-mesenchymal
      transition, with resultant tubular atrophy, fibrosis and renal failure.
      Inhibition of MMP-2, specifically in the early, prefibrotic stages of disease may
      offer an additional approach for treatment of these disabling disorders.

PMID- 16891620
TI  - A region in the dystrophin gene major hot spot harbors a cluster of deletion
      breakpoints and generates double-strand breaks in yeast.
AB  - Deletions within the dystrophin gene (DMD) account for >70% of mutations leading
      to Duchenne and Becker muscular dystrophies (DMD and BMD). Deletion breakpoints
      were reported to be scattered within regions that also represent meiotic
      recombination hot spots. Recent studies indicates that deletion junctions arise
      from nonhomologous end joining (NHEJ), a major pathway for repairing DNA double
      strand breaks (DSBs) in mammals. Here we show that a region in intron 47 (i.e., a
      major deletion hot spot in the DMD gene) generates DSBs during meiosis in yeast
      and harbors a cluster of previously sequenced deletion breaks. Mapping of
      breakpoints in 26 BMD/DMD patients indicated that the frequency of breakpoint
      occurrence around this region is 3-fold higher than expected by chance. These
      findings suggest that DSBs mediate deletion formation in intron 47 and possibly
      account for the high frequency of meiotic recombination in the region.
      Statistical analysis indicated the presence of at least one other breakpoint
      cluster in intron 47. Taken together, these results suggest that the primary
      events in deletion formation occur within discrete regions and that the scattered
      breakpoint distribution reflects both a variable degree of DSB end processing and
      the availability of a small (compared to the huge regions involved) deletion
      junction sample.

PMID- 16891622
TI  - Neuropeptide Y induces migration, proliferation, and tube formation of
      endothelial cells bimodally via Y1, Y2, and Y5 receptors.
AB  - Previously we discovered that NPY induces ischemic angiogenesis by activating Y2
      and Y5 receptors. The receptors that mediate specific steps of the complex
      process of angiogenesis are unknown. Here, we studied in vitro NPY receptors
      subtypes involved in migration, proliferation, and differentiation of human
      endothelial cells. In cells that expressed Y1, Y2, and Y5 receptors, NPY
      bimodally stimulated migration and proliferation with a 2-fold increase at 10(
      12) M and 10(-8) M (high- and low-affinity peaks, respectively). Preincubation of
      cells with NPY up-regulated the Y5 receptor and markedly enhanced endothelial
      cell migration and proliferation. NPY-induced endothelial cell migration was
      mimicked by agonists and fully blocked by antagonists for any specific NPY
      receptors (Y1, Y2, or Y5), while proliferation was blocked by any two antagonists
      (Y1+Y2, Y1+Y5, or Y2+Y5), and capillary tube formation on Matrigel was blocked by
      all three (Y1+Y2+Y5). Thus, NPY-induced angiogenesis requires participation of
      Y1, Y2, and Y5 receptor subtypes, with the Y5 receptor acting as an enhancer. We
      propose that these receptors form heteromeric complexes, and the Y1/Y2/Y5
      receptor oligomer may be the uncloned Y3 receptor.

PMID- 16891621
TI  - Nitric oxide regulates mitochondrial oxidative stress protection via the
      transcriptional coactivator PGC-1alpha.
AB  - Nitric oxide (NO) has both prooxidant and antioxidant activities in the
      endothelium; however, the molecular mechanisms involved are still a matter of
      controversy. PGC-1alpha [peroxisome proliferators-activated receptor (PPAR) gamma
      coactivator 1-alpha] induces the expression of several members of the
      mitochondrial reactive oxygen species (ROS) detoxification system. Here, we show
      that NO regulates this system through the modulation of PGC-1alpha expression.
      Short-term (<12 h) treatment of endothelial cells with NO donors down-regulates
      PGC-1alpha expression, whereas long-term (>24 h) treatment up-regulates it.
      Treatment with the NOS inhibitor l-NAME has the opposite effect. Down-regulation
      of PGC-1alpha by NO is mediated by protein kinase G (PKG). It is blocked by the
      soluble guanylate cyclase (sGC) inhibitor ODQ and the PKG inhibitor KT5823, and
      mimicked by the cGMP analog 8-Br-cGMP. Changes in PGC-1alpha expression are in
      all cases paralleled by corresponding variations in the mitochondrial ROS
      detoxification system. Cells that transiently overexpress PGC-1alpha from the
      cytomeglovirus (CMV) promoter respond poorly to NO donors. Analysis of tissues
      from eNOS(-/-) mice showed reduced levels of PGC-1alpha and the mitochondrial ROS
      detoxification system. These data suggest that NO can regulate the mitochondrial
      ROS detoxification system both positively and negatively through PGC-1alpha.

PMID- 16891623
TI  - The myth of peer influence in adolescent smoking initiation.
AB  - The widespread belief that peer influence is the primary cause of adolescent
      smoking initiation is examined and called into question. Correlational and
      longitudinal studies purporting to demonstrate peer influence are analyzed, and
      their limitations described. Qualitative interview studies of adolescent smoking
      initiation are presented as depicting the more complex role of the peer context.
      Finally, a new model of the role of peers in smoking initiation is offered, with
      an emphasis on how adolescents' characteristics lead to the selection of their
      friends, who then provide a peer context that may or may not support smoking.

PMID- 16891624
TI  - Ethnic differences in decisional balance and stages of mammography adoption.
AB  - Behavioral theories developed through research with mainstream, English-speaking
      populations have been applied to ethnically diverse and underserved communities
      in the effort to eliminate disparities in early breast cancer detection. This
      study tests the validity of the transtheoretical model (TTM) decisional balance
      measure and the application of the TTM stages of change in a multiethnic,
      multilingual sample. A random sample of 1,463 Filipino, Latino, African American,
      Chinese, and White women aged 40 to 74 completed a phone survey of mammography
      beliefs and practices. Consistent with the TTM and independent of ethnicity,
      decisional balance was associated with mammography stage in all five ethnic
      groups when controlling for socioeconomic and other factors. In addition, having
      private insurance and a regular physician and being a long-time resident in the
      United States were positively associated with mammography maintenance. The
      application of the TTM for mammography is supported in a multiethnic and
      multilingual sample.

PMID- 16891625
TI  - ChREBP binding to fatty acid synthase and L-type pyruvate kinase genes is
      stimulated by glucose in pancreatic beta-cells.
AB  - Pancreatic beta-cell dysfunction is central to the pathogenesis of type 2
      diabetes and may involve secretory failure through glucolipotoxity. The relative
      importance of the transcription factors carbohydrate-responsive element binding
      protein (ChREBP), sterol-responsive element binding protein-1c (SREBP-1c), and
      upstream stimulatory factor (USF) in the induction of lipogenic genes by glucose
      remains unclear. By confocal imaging, we show that ChREBP translocates to the
      nucleus in MIN6 beta cells in response to glucose. Both ChREBP and SREBP-1c were
      required for the induction of the fatty acid synthase (FAS) promoter by glucose,
      and chromatin immunoprecipitation (ChIP) assay revealed that glucose induced the
      binding of both ChREBP and SREBP-1c to the FAS promoter without affecting USF2
      binding. By contrast, ChIP assay revealed that high glucose prompted direct
      binding of ChREBP, but not SREBP-1c or USF2, to the liver-type pyruvate kinase (L
      PK) promoter. This event was indispensable for the induction of the L-PK gene by
      glucose, as demonstrated by RNA silencing, single-cell promoter analysis, and
      quantitative real-time PCR. We conclude that ChREBP is a critical regulator of
      lipogenic genes in the beta cell and may play a role in the development of
      glucolipotoxicity and beta cell failure through alteration of gene expression in
      type 2 diabetes.

PMID- 16891626
TI  - Doxycycline alters the expression of inflammatory and immune-related cytokines
      and chemokines in human endometrial cells: implication in irregular uterine
      bleeding.
AB  - BACKGROUND: Increased production of pro-inflammatory mediators is considered
      central in the manifestation of events leading to irregular uterine bleeding in
      progestin-only contraceptive users. Evidence suggests that in addition to its
      antimicrobial property, doxycycline (Dox) acts as an anti-inflammatory agent
      mainly through the suppression of pro-inflammatory mediators. METHODS: We tested
      this hypothesis in the endometrial environment using an in vitro model consisting
      of isolated human endometrial glandular epithelial and stromal cells and a human
      endometrial surface (HES) epithelial cell line cultured under defined conditions.
      RESULTS: We found that Dox at doses ranging from 1 to 100 microg/ml had a limited
      growth-inhibitory effect on these cells, whereas Dox in a dose-dependent manner
      inhibited the production of tumour necrosis factor-alpha (TNF-alpha). Using
      multiplex cytokine/chemokine protein analysis to test a broader range of Dox
      activity, we found that Dox at 25 microg/ml either alone or in the presence of
      17beta-estradiol (E2), medroxyprogesterone acetate (MPA) and E2+MPA (10(-8) M) as
      well as TNF-alpha (25 ng/ml), representing the endometrial environment exposed to
      contraceptives as well as inflammatory conditions, respectively, altered the
      production of multiple cytokines and chemokines as compared with untreated
      controls. These actions of Dox occurred in cell-, ovarian steroid- and
      cytokine/chemokine-dependent manners. Although Dox reduced the regulatory action
      of steroids on the production of these cytokines/chemokines, it was less
      effective on TNF-alpha-treated cells. CONCLUSIONS: The results support the
      hypothesis that Dox, by modulating the endometrial expression of multiple
      inflammatory-related cytokines/chemokines in a cell- and cytokine/chemokine
      dependent manner, may have a therapeutic potential in patients experiencing
      irregular uterine bleeding, in particular in progestin-dominant contraceptive
      users.

PMID- 16891627
TI  - Leptin induces an Apc genotype-associated colon epithelial cell chemokine
      production pattern associated with macrophage chemotaxis and activation.
AB  - Leptin is an adipocyte-derived cytokine associated with obesity and inflammation
      recently shown to influence colon epithelial cell fate and colon inflammation.
      Thus, the purpose of this study is to investigate the influences of leptin
      exposure on the production of proinflammatory signals by a model of normal [YAMC
      (Apc+/+)] and preneoplastic [IMCE (ApcMin/+)] colon epithelial cells. Here, we
      characterize the production of specific CC and CXC chemokines by IMCE and YAMC
      cells using an antibody-based cytokine array. Further, since epithelial cells are
      hypothesized to be accessory to the inflammatory response, we assessed the
      ability of supernants from leptin-exposed colon epithelial cells to activate
      macrophage chemotaxis and nitric oxide production. Both YAMC and IMCE cells
      produced the following chemokines from the CC family; MCP-1, MIP-3alpha, TCA-3,
      CTACK and RANTES. These cell lines also produced the following CXC chemokines;
      MIP-2, CXCL18, KC and LIX. Conditioned media from leptin-treated YAMC and IMCE
      cells induced nitric oxide production by macrophages (P<0.05). However, only
      conditioned media from leptin-treated IMCE cells induced macrophage chemotaxis
      (P<0.05). These data imply that preneoplastic but not normal cells may
      selectively attract immune cells that promote their survival and transformation.
      Taken together with our previous data, we conclude that leptin promotes the
      proliferation of a model of preneoplastic cells (IMCE) and induces the production
      of chemokines which may activate macrophages and promote macrophage cell
      chemotaxis. These data provide a rational basis for leptin-induced cross-talk
      between preneoplastic epithelial cells and immune cells that may influence the
      promotional phase of carcinogenesis.

PMID- 16891629
TI  - Pharmacodynamics of dalbavancin studied in an in vitro pharmacokinetic system.
AB  - OBJECTIVES: The antibacterial effect of dalbavancin was studied against
      Staphylococcus aureus using stepwise declining concentrations designed to model a
      range of free drug concentrations observed in human serum. METHODS: Initial
      concentrations ranged from 0.6 to 21 mg/L and experiments were conducted over 240
      h. Three vancomycin-susceptible and one vancomycin-intermediate strain of S.
      aureus were used. RESULTS AND CONCLUSIONS: Dalbavancin showed non-concentration
      dependent killing against the three vancomycin-susceptible strains in the range 3
      21 mg/L and the vancomycin-intermediate strain at 15 and 21 mg/L. AUC/MIC could
      be related to antibacterial effect. The AUC/MIC for a bacteriostatic effect was
      36 at 24 h, 55 at 120 h and 100 at 240 h. A larger AUC/MIC was required to
      produce a 2 log reduction in counts, being 214 at 24 h, 195 at 120 h and 331 at
      240 h.

PMID- 16891628
TI  - Specific mutations in HIV-1 gp41 are associated with immunological success in HIV
      1-infected patients receiving enfuvirtide treatment.
AB  - OBJECTIVES: To investigate gp41 variability and correlation with viro
      immunological parameters in 54 HIV-1-infected patients receiving enfuvirtide
      added as single active drug to a failing regimen. METHODS: One hundred and two
      HIV-1 gp41 sequences and clinical follow-up from 54 enfuvirtide-treated patients
      were analysed from baseline to week 36 of treatment. The association of mutations
      with viraemia/CD4 count was assessed by Mann-Whitney test. RESULTS: The addition
      of enfuvirtide to the failing regimen induced at week 4 a viraemia decrease from
      5.1 to 4.3 log(10)/mL (P = 0.0002) and a CD4 increase from 48 to 106 cells/mm(3)
      (P = 0.008). While viraemia rebounded to 4.8 and 4.6 log(10)/mL at week 12 and
      36, respectively, CD4 continued to increase to 136 cells/mm(3) at week 36.
      Enfuvirtide resistance mutations, rarely found at baseline, occurred in 45/54
      (83.3%) enfuvirtide-treated patients. V38A/E were the most represented mutations
      at all time-points. The presence of V38A/E was significantly associated with a
      4.5-fold CD4 increase from baseline to week 24 and with a 6-fold increase at week
      36 (P = 0.004 and 0.02 compared without V38A/E, respectively), without
      significant correlation with viraemia. In contrast, Q40H + L45M (present in six
      enfuvirtide-treated patients at week 36) correlated with CD4 loss from baseline
      to week 36 (P = 0.02), without significant correlation with viraemia. Mutation
      N126K (observed in six enfuvirtide-treated patients, never found at baseline)
      abrogates the fourth gp41 glycosylation site and correlates with a 2.1-fold CD4
      increase at week 24. CONCLUSIONS: Specific enfuvirtide resistance mutations
      (V38A/E) are associated with a sustained CD4 increase, without remarkable effects
      upon viraemia. This CD4 recovery, due to virus- and immune-mediated mechanisms
      most probably not applicable to protease/reverse transcriptase inhibitors, is
      important for innovative therapeutic strategies.

PMID- 16891630
TI  - Mutators among CTX-M beta-lactamase-producing Escherichia coli and risk for the
      emergence of fosfomycin resistance.
AB  - OBJECTIVES: Fosfomycin is a possible oral treatment for lower urinary tract
      infections caused by Escherichia coli with CTX-M extended-spectrum beta
      lactamases but is vulnerable to mutational resistance. Hypermutability among
      natural E. coli populations might facilitate the emergence of resistance to
      fosfomycin. We therefore examined the prevalence of mutators amongst urinary
      isolates of E. coli producing CTX-M beta-lactamases. METHODS: Urinary E. coli
      isolates with CTX-M beta-lactamases (n = 220) were screened for resistance to
      both rifampicin and fosfomycin, as well as a mutator phenotype, by rifampicin and
      fosfomycin disc assays. Mutation frequencies for 10 isolates, identified as
      mutators by the initial disc screen, were determined in triplicate on agar with
      rifampicin or fosfomycin at 4x MIC and with fosfomycin or nitrofurantoin at 256
      mg/L. RESULTS: The disc screen identified 10 likely mutators and quantitative
      tests indicated that 9 of these had mutation frequencies of 8.0 x 10(-6)-1.5 x
      10(-4) for fosfomycin and 0.1-2.3 x 10(-6) for rifampicin. These mutators were
      diverse in terms of PFGE type and 4 of the 10 were confirmed as strong mutators
      with rifampicin and fosfomycin. Only the strongest mutator isolate and
      hypermutable MutS(-) control strain consistently gave single-step mutants
      resistant to 256 mg/L fosfomycin. No nitrofurantoin-resistant mutants were
      selected from any isolate, although they could be selected from the hypermutable
      MutS(-) control strain. CONCLUSIONS: Mutator phenotypes were found among E. coli
      expressing CTX-M beta-lactamases and were independent of strain type. These had
      an increased propensity to fosfomycin resistance.

PMID- 16891631
TI  - Mutations conferring zanamivir resistance in human influenza virus N2
      neuraminidases compromise virus fitness and are not stably maintained in vitro.
AB  - BACKGROUND: Viruses resistant to zanamivir have been generated in vitro, but no
      resistant virus has yet been isolated from a zanamivir-treated immunocompetent
      patient. In contrast most resistant viruses isolated from oseltamivir-treated
      patients correspond to those selected in vitro. However, despite mutations being
      in conserved residues in the neuraminidase (NA) they do not confer resistance in
      all NA subtypes. OBJECTIVES AND METHODS: We have used reverse genetics and the
      recombinant baculovirus expression system for investigating reasons for the lack
      of isolation of zanamivir-resistant H3N2 viruses and for further exploring
      subtype-specific oseltamivir resistance. RESULTS: H3N2 viruses generated by
      reverse genetics with H274Y, R292K E119V and E119D mutations were rescued. Those
      with E119G, E119A or R152K mutations could only be rescued in the presence of
      exogenous NA and after passage in the absence of exogenous NA only isolates that
      had reverted to the wild-type NA or, surprisingly, E119G/A to E119V NA were
      isolated. Mutations conferring zanamivir resistance significantly affected enzyme
      activity, virus replication or NA thermal stability. E119V viruses were stable
      and grew to similar titres as wild-type virus, consistent with their isolation
      from oseltamivir-treated patients. Mutations conferring oseltamivir resistance in
      N1 (H274Y) and B (R152K) NAs also conferred resistance in recombinant G70C N9 NA
      expressed in insect cells. CONCLUSIONS: These data suggest that zanamivir
      resistant H3N2 viruses may not readily arise in vivo due to their poor viability.
      The G70C N9 NA may also provide a useful model for understanding the structural
      basis of subtype-specific drug resistance.

PMID- 16891632
TI  - Comment on: guidelines for the prevention of endocarditis: report of the Working
      Party of the British Society for Antimicrobial Chemotherapy.

PMID- 16891633
TI  - Proteomic analysis of a penicillin-tolerant rgg mutant strain of Streptococcus
      pyogenes.
AB  - OBJECTIVES: To determine whether the transcriptional regulator Rgg contributes to
      penicillin-induced killing of Streptococcus pyogenes by altering a regulatory
      response to penicillin. METHODS: Penicillin-induced killing of a wild-type and
      isogenic rgg mutant strain was assessed in broth and solid media and in the
      presence of cerulenin, which inhibits fatty acid biosynthesis (FAB). Proteins
      from wild-type and rgg mutant cultures, either exposed to penicillin or not, were
      characterized by two-dimensional gel electrophoresis. Proteins of interest were
      identified with tandem mass spectrometry. RESULTS: The MIC of penicillin was
      0.012 mg/L for both the wild-type strain NZ131 and an isogenic rgg mutant strain.
      The wild-type strain lost 1.9 log(10) cfu/mL ( approximately 80-fold) after 24 h
      of exposure to 0.024 mg/L penicillin compared with controls; however, the mutant
      strain lost 0.3 log(10) cfu/mL ( approximately 2-fold) compared with controls.
      Changes in the proteome of wild-type and mutant cultures were assessed 1 and 4 h
      after exposure to penicillin. One hour exposure was associated with increased
      abundance (P < 0.05) of 12 proteins associated with FAB, the pentose phosphate
      pathway, glycolysis and stress responses in the wild-type strain. The abundance
      of 8 of 12 of these proteins was greater in samples obtained from the mutant
      strain, even prior to penicillin exposure. After 4 h of exposure, the abundance
      of 16 proteins was altered in one or both strains; however, a clear functional
      relationship was not evident. The addition of cerulenin slightly enhanced
      penicillin-induced killing of wild-type strain, which supported the proteomic
      results. CONCLUSIONS: The results suggest that penicillin-independent changes in
      the cytoplasmic proteome of an rgg mutant strain of NZ131 confer tolerance to
      penicillin-mediated killing.

PMID- 16891634
TI  - Hyperbaric articaine for day-case spinal anaesthesia.
AB  - BACKGROUND: Articaine and lidocaine are clinically very similar suggesting that
      articaine could be suitable for day-case spinal anaesthesia. A dose-response
      study with articaine in ambulatory spinal anaesthesia was therefore performed.
      METHODS: In this randomized double-blind study, 90 day-case surgery patients
      received spinal anaesthesia with 60 mg (A60), 84 mg (A84) or 108 mg (A108) of
      hyperbaric articaine hydrochloride. Sensory block was tested with pinprick and
      motor block on a modified Bromage scale. A structured interview was performed on
      the first and seventh postoperative days. RESULTS: Sensory block reached the T10
      dermatome in a median (range) of 5 (5-10) and was maintained at this level for 70
      (35-145), 70 (15-115) and 85 (20-115) min in the A60, A84 and A108 groups,
      respectively. Six patients in the A108 group, two in the A84 group and one in the
      A60 group had maximum spread of analgesia to T(1) or higher (NS). Patients in the
      A108 group needed more medication for hypotension (P=0.018), had more often
      nausea and vomiting (P=0.027), took oral fluids later (P=0.031) and both sensory
      block recovery [median (range)] [2.5 (2-4.5) h] (P=0.017) and motor block
      recovery [2 (1.3-4) h] (P=0.009) were delayed. No patients in the A108 group
      needed opioid intraoperatively while fentanyl was needed in 5 (17%) and 2 (7%)
      patients in the A60 and A84 groups, respectively. Discharge criteria were
      attained in approximately 4.5 h after articaine injection (NS) and no drug
      related sequelae were observed. CONCLUSIONS: Hyperbaric articaine 60 and 84 mg
      resulted in spinal anaesthesia allowing surgery of the lower extremities for
      about 1 h. Recovery was rapid. Use of 108 mg of articaine is not recommended
      because of frequent extensive cephalad spread of the block, accompanied by
      arterial hypotension and nausea.

PMID- 16891636
TI  - Evaluation of genetic damage in operating room personnel exposed to anaesthetic
      gases.
AB  - Information on potential genetic damage in humans after exposure to waste
      anaesthetic gases in Indian hospitals is scarce. To evaluate the possible
      genotoxic effects of waste anaesthetic gases, the chromosomal aberrations
      analysis and comet assay were studied in peripheral blood lymphocytes in 45
      operating room personnel currently employed at a hospital in South India. In
      addition, the micronucleus test on buccal epithelial cells was also carried out
      in the same subjects. The exposed group was compared with a group of 45 non
      exposed group, matched by age, sex, alcohol consumption and smoking habits. The
      results showed a statistically significant increase in DNA damage by the comet
      assay in the exposed group. Chromosome aberrations and micronucleus frequencies
      also increased significantly in the study subjects in comparison to the controls.
      Analysis of variance showed that smoking had a significant effect on DNA mean
      tail length, whereas alcohol consumption, duration of exposure to anaesthetic
      agents, age and gender had no significant effect. All the confounding factors had
      significant effect by the micronucleus test. However, smoking, alcohol
      consumption, age, gender and years of exposure showed no significant effect by
      the chromosome aberrations test. The results of our study suggest that exposure
      to waste anaesthetic gases has the potential to cause changes in the human
      genome.

PMID- 16891635
TI  - TGFbeta receptor II gene deletion in leucocytes prevents cerebral vasculitis in
      bacterial meningitis.
AB  - In bacterial meningitis, chemokines lead to recruitment of polymorphonuclear
      leucocytes (PMN) into the CNS. At the site of infection in the subarachnoid
      space, PMN release reactive oxygen species, reactive nitrogen intermediates (RNI)
      and interleukin-1beta (IL-1beta). Although these immune factors assist in
      clearance of bacteria, they also result in neuronal injury associated with
      meningitis. Transforming growth factor beta (TGFbeta) is a potent deactivator of
      PMN and macrophages since TGFbeta suppresses the production of ROI, RNI and IL-1.
      Here, we report that the deletion of the TGFbeta receptor II gene in PMN enhances
      PMN recruitment into the CNS of mice with Streptococcus pneumoniae meningitis.
      This was associated with more efficient clearance of bacteria, and almost
      complete prevention of intracerebral necrotizing vasculitis. Differences in PMN
      in the CNS of infected control mice and mice lacking TGFbeta receptor II were not
      explained by altered expression of chemokines acting on PMN. Instead, TGFbeta was
      found to impair the expression of L (leucocyte)-selectin on PMN from control mice
      but not from mice lacking TGFbeta receptor II. L-selectin is known to be
      essential for PMN recruitment in bacterial meningitis. We conclude that defective
      TGFbeta signalling in PMN is beneficial in bacterial meningitis by ameliorating
      migration of PMN and bacterial clearance.

PMID- 16891637
TI  - Structure of beta-1,3-xylooligosaccharides generated from Caulerpa racemosa var.
      laete-virens beta-1,3-xylan by the action of beta-1,3-xylanase.
AB  - Recently we reported the molecular cloning and characterization of a novel beta
      1,3-xylanase from the marine bacterium Vibrio sp. AX-4 [Kiyohara et al. (2005)
      Biochem. J. 388, 949-957]. We report here the structural analysis of
      oligosaccharides generated from beta-1,3-xylan of a siphonous green alga,
      Caulerpa racemosa var. laete-virens, by the action of beta-1,3-xylanase. The
      enzyme degraded the polysaccharide producing oligosaccharides with different
      R(f)s on TLC (EX2-EX5). Sugar component, linkage, and MALDI-TOF-MS analyses
      revealed that EX2 and EX3 were Xyl-1,3-Xyl and Xyl-1,3-Xyl-1,3-Xyl, respectively.
      On the other hand, EX4 was a mixture of Glc-1,3-Xyl-1,3-Xyl, Xyl-1,4-Xyl-1,3-Xyl
      and Xyl-1,3-Xyl-1,4-Xyl, while EX5 was a mixture of tetra-saccharides containing
      3-substitued Glc in addition to the same components of EX4. Branching was not
      likely present in EXOs prepared from the polysaccharide by the enzyme. These
      results strongly suggest that the C. racemosa beta-1,3-xylan is a linear
      heteropolysaccharide containing 1,3-Glc and 1,4-Xyl both of which are thought to
      be located within a beta-1,3-Xyl chain and linked via covalent bonds. This report
      indicates the usefulness of the enzyme for the structural analysis of beta-1,3
      xylan.

PMID- 16891639
TI  - Albuminuria in acute tubular necrosis.

PMID- 16891638
TI  - Obituary to analgesic nephropathy--an autopsy study.
AB  - BACKGROUND: To determine whether classic analgesic nephropathy with renal
      papillary and urothelial capillary sclerosis could still be detected at autopsy
      in the beginning of the 21st century, the present study which is similar to a
      previous one performed in 1980 was undertaken as suggested by the Ad Hoc
      Committee of the International Study Group on Analgesics and Nephropathy.
      METHODS: Consecutive autopsies of 616 adults performed at the Basle Institute of
      Pathology between November 2000 and February 2002 were analysed. Tissue samples
      of renal cortex and papilla of 1220 kidneys and of each ureter and main renal
      artery available were subjected to a very careful and meticulous study using
      classical histopathological methodology. RESULTS: A number of lesions was found
      macroscopically but not a single case of papillary necrosis or analgesic
      nephropathy could be detected preceding histological analysis. Histologically,
      the most frequent lesions were vascular in 57.8% of kidneys followed by
      glomerular lesions in 13.1% (mostly diabetic glomerulosclerosis). Tubulo
      interstitial lesions, mostly pyelonephritis were detected in 9.3% with only a
      single case of classic analgesic nephropathy with bilateral complete papillary
      necrosis and ureteral capillary sclerosis in a female who had received a renal
      transplant 14 years before her demise at the age of 67. In another five cases,
      complete papillary necrosis was detected associated with pyelonephritis,
      hydronephrosis or in completely shrunken kidneys. However, in the absence of
      capillary sclerosis, a histopathological diagnosis of classic analgesic
      nephropathy could not be made in any of these five cases. CONCLUSIONS: The Basle
      autopsy prevalence of analgesic nephropathy decreased continuously from some 3%
      in 1980 to 0.2% in 2000 as shown by the present study. Similarly, capillary
      sclerosis of the urinary tract, the initiating event in the pathophysiology of
      papillary necrosis and analgesic nephropathy and the histological hallmark of the
      effect of toxic metabolites of phenacetin in analgesic abusers decreased from 4%
      of autopsy cases between 1978 and 1980 to the single case of the present study
      observed at the end of 2000. Thus, the classic analgesic nephropathy has
      disappeared some 20 years after the removal of phenacetin from the analgesic
      market despite the fact that mixed analgesics containing paracetamol, the main
      metabolite of phenacetin, have continued to be popular and widely used drugs.

PMID- 16891640
TI  - Early assessment of renal resistance index after kidney transplant can help
      predict long-term renal function.
AB  - BACKGROUND: Color Doppler ultrasonography of intrarenal arterial resistance index
      (RI), performed early after kidney transplant, has proven to reliably predict
      short-term allograft function. The aim of this study was to assess whether it
      could also predict long-term renal function. METHODS: We retrospectively analysed
      76 kidney transplant patients who underwent RI assessment within 1 month after
      the transplant, subdivided into two groups according to RI values, lower (group
      A) or higher (group B) than its median value (0.635). RESULTS: Compared with
      group A subjects, the patients of group B were older at the time of transplant
      (42 +/- 9 vs 35 +/- 8 years; P = 0.001), the donor age was also older (41 +/- 16
      vs 33 +/- 13 years; P = 0.02) and had a slightly higher proteinuria (0.54 +/- 0.5
      vs 0.32 +/- 0.2 g/24 h; P = 0.02). Serum creatinine, ciclosporin or tacrolimus
      trough level, arterial blood pressure, number of human leukocyte antigen (HLA)
      mismatches, anti-hypertensive medications and incidence of delayed graft function
      were not significantly different between the two groups. By univariate analysis,
      RI turned out to directly correlate with the recipient age, donor age and daily
      proteinuria (P = 0.007, P = 0.0007 and P = 0.02, respectively). Multivariate
      analysis showed that only donor and recipient age maintained their independent
      predictive value on RI. Kaplan-Meier analysis, considering a serum creatinine
      increase >50% as the endpoint of the study, showed a statistically significant
      different graft survival in the two groups (log-rank test = 5.489; P = 0.01). The
      univariate relative risk of deterioration of graft function among patients with
      higher RI was 3.77. Proteinuria and recipient age increased the risk as well.
      CONCLUSIONS: Our data seem to suggest that early determination of RI can help
      predict long-term graft function in kidney transplant recipients.

PMID- 16891641
TI  - Emphysematous pyelonephritis treated with percutaneous catheter drainage and
      antibiotics.

PMID- 16891642
TI  - The efficacy of intravenous darbepoetin alfa administered once every 2 weeks in
      chronic kidney disease patients on haemodialysis.
AB  - BACKGROUND: It is becoming increasingly more common to administer intravenous
      (i.v.) darbepoetin alfa to haemodialysis (HD) patients at less frequent dosing
      intervals in routine clinical practice. This study investigated extending the
      dosing interval for i.v. darbepoetin alfa treatment from once a week (QW) to once
      every 2 weeks (Q2W) at the same dose in order to maintain target haemoglobin (Hb)
      concentrations (11-13 g/dl). METHODS: Stable HD patients in routine clinical
      practice receiving i.v. darbepoetin alfa QW for a period of 6 months (n = 105)
      (treatment period 1) were switched to i.v. Q2W darbepoetin alfa for a further 6
      months (treatment period 2) (n = 90). The dose of i.v. darbepoetin alfa was
      titrated to maintain Hb concentrations between 11 and 13 g/dl throughout the full
      12-month study period. RESULTS: The mean change in Hb for treatment period 2 was
      0.04 +/- 1.1 g/dl (+/-SD), which was not clinically relevant (11.7 +/- 0.8 g/dl
      vs 11.7 +/- 1.0 g/dl; P = 0.8). The mean weekly doses of darbepoetin alfa were
      similar throughout the treatment periods (34.0 +/- 17.1 microg/week vs 32.1 +/-
      17.3 microg/week; P = 0.3, respectively for QW and Q2W dosing). Intravenous
      darbepoetin alfa was well tolerated. CONCLUSIONS: The treatment of renal anaemia
      in HD patients with i.v. Q2W darbepoetin alfa effectively and safely maintains Hb
      concentrations at a less frequent dosing regimen than observed with QW
      administration. Dose requirements for i.v. darbepoetin alfa administered QW or
      Q2W were not different. The results of this study demonstrate that i.v.
      darbepoetin alfa administered Q2W is an effective regimen for HD patients
      requiring anaemia treatment in routine clinical practice.

PMID- 16891643
TI  - Calcareous degeneration of the eye--an unusual complication of uraemic
      hyperparathyroidism.

PMID- 16891644
TI  - Adriamycin nephropathy in severe combined immunodeficient (SCID) mice.

PMID- 16891645
TI  - Glucose infusion test (GIT) compared with the saline dilution technology in
      recirculation measurements.
AB  - BACKGROUND: Glucose infusion test (GIT) is a new method to measure vascular
      access recirculation (R) based on basal glucose increase in the arterial blood
      line after a 20% glucose bolus (5 ml) into the venous chamber. METHODS: We
      compared GIT with the ultrasound dilution method (HD01, Transonic Systems Inc.,
      USA) in a circuit reproducing in vitro the phenomenon of R. We repeated the
      comparison in 162 chronic haemodialysis patients (133 fistulae, 17 central venous
      catheters, 12 prosthetic grafts). RESULTS: In vitro, we determined the timing for
      C2 sampling: QB 200 ml/min, C2 16-20 s; QB 300 ml/min, C2 13-17 s; QB 400 ml/min,
      C2 9-12 s. GIT showed no false positives nor false negatives (100% specificity
      and sensitivity) while HD01 did not recognize three cases with R=5% (91%
      sensitivity) and it yielded no false positive (100% specificity). The Bland
      Altman analysis showed a bias of 0.2+/-1.3% and 1.3+/-2.9% for GIT and HD01,
      respectively. In vivo, only 16 out of 162 patients were found positive with both
      methods (GIT 13.5+/-13%; HD01 16.3+/-15%; P=NS) while three patients with minimal
      R (GIT 3.2%) were not recognized by HD01 although a low R peak was clearly
      evident and repeatable on the laptop plot. The Bland-Altman analysis showed an
      overall bias of 0.2+/-1.7% to the limits of agreement=-3.1 and 3.6% (n=162) and
      no correlation between the difference and the mean of positive tests. The pooled
      coefficient of variation of positive cases was 13.3 and 18.1% for GIT and HD01,
      respectively. DISCUSSION: Our in vitro study showed a good performance of GIT and
      its better sensitivity compared to HD01. These results were confirmed in vivo
      with only 3/162 discordant results due to a low R under the HD01 limit of
      detection (R=5%). In conclusion, the GIT proved to be a very accurate screening
      test for R, with a very low threshold of detection. In addition, it is simple,
      user-friendly and inexpensive.

PMID- 16891646
TI  - Catheter-related bacteraemia in haemodialysis patients with HIV infection.
AB  - BACKGROUND: Tunnelled catheters are used for dialysis in over 25% of
      haemodialysis (HD) patients and are a major risk factor for bacteraemia. HIV
      positive patients may be at particularly increased risk of catheter-related
      bacteraemia (CRB) due to their immunocompromised state. The present case
      controlled study compared catheter-related bacteraemia with HIV-positive and HIV
      negative haemodialysis patients. METHODS: Using a prospective computerized
      vascular access database, we identified 33 HIV-positive haemodialysis patients
      who had a tunneled dialysis catheter placed during a 6.5-year period. Their
      catheter outcomes were compared with those observed in 55 age-, sex- and access
      date-matched control haemodialysis patients. RESULTS: The two groups were similar
      in terms of age, sex, diabetes, hypertension and peripheral vascular disease, but
      the HIV patients were more likely to be black (94 vs 76%, P=0.03). CRB occurred
      in 52% of the HIV patients and 49% of the controls (P=0.83). The median infection
      free catheter survival was similar in HIV-positive and negative patients (165 vs
      119 days, P=0.12). Among patients with CRB, the likelihood of a Gram-negative
      infection was similar in both groups (18 vs 30%, P=0.37). However, polymicrobial
      CRB was more likely in HIV patients (41 vs 15%, P=0.049). HIV-positive patients
      were more likely to be hospitalized for treatment of CRB than HIV-negative
      patients (29 vs 7%, P=0.05). CONCLUSION: CRB is equally likely in HIV-positive
      and control haemodialysis patients. However, CRB is likely to be more severe in
      HIV-positive patients, as judged from the greater likelihood of polymicrobial
      infection and of hospitalization.

PMID- 16891648
TI  - TAK-603, an anti-inflammatory compound, reduces crescentic glomerulonephritis and
      preserves renal function in WKY rats.
AB  - BACKGROUND: The therapeutic efficacy of the regulation of T helper (Th)-1
      predominant immune responses remains to be investigated. Therefore, the effects
      of the anti-inflammatory compound TAK-603 were investigated in a model of
      crescentic glomerulonephritis induced by a small dose of nephrotoxic serum in
      Wistar-Kyoto rats. METHODS: TAK-603 (50 mg/kg body weight) was administered
      orally, starting at the time of induction of glomerulonephritis. In group 1, the
      drug was administered daily for the initial 6 days. TAK-603 was administered on
      day 0 only in group 2, and from day 3 to 5 in group 3. In each group, nephritic
      rats were killed on days 6 and 56. RESULTS: In group 1 consisting of rats treated
      with TAK-603 daily from day 0 to 5, glomerular damage, including crescent
      formation, was improved on day 6, with reductions in the numbers of CD4, CD8 and
      ED-1 positive cells, as well as in urinary protein excretion. Protein and
      transcript levels of Th1 cytokines in the diseased kidneys were markedly
      decreased by TAK-603 treatment. Renal pathology, including glomerulosclerosis and
      interstitial fibrosis, was ameliorated and proteinuria was markedly decreased.
      Elevated levels of serum creatinine showed concomitant improvement. In group 3,
      in which treatment was initiated shortly after the appearance of glomerular
      abnormalities, glomerular damage was also diminished, resulting in a decrease in
      urinary protein excretion. Treatment only on the first day in group 2, partially
      rescued renal dysfunction. CONCLUSIONS: These results suggest the possible
      therapeutic application of inhibition of Th1-predominant immune responses in
      progressive crescentic glomerulosclerosis.

PMID- 16891647
TI  - Weekly low-dose treatment with intravenous iron sucrose maintains iron status and
      decreases epoetin requirement in iron-replete haemodialysis patients.
AB  - BACKGROUND: Haemodialysis patients need sustained treatment with intravenous iron
      because iron deficiency limits the efficacy of recombinant human epoetin therapy
      in these patients. However, the optimal intravenous iron maintenance dose has not
      been established yet. METHODS: We performed a prospective multicentre clinical
      trial in iron-replete haemodialysis patients to evaluate the efficacy of weekly
      low-dose (50 mg) intravenous iron sucrose administration for 6 months to maintain
      the iron status, and to examine the effect on epoetin dosage needed to maintain
      stable haemoglobin values in these patients. Fifty patients were enrolled in this
      prospective, open-label, single arm, phase IV study. RESULTS: Forty-two patients
      (84%) completed the study. After 6 months of intravenous iron sucrose treatment,
      the mean ferritin value showed a tendency to increase slightly from 405 +/- 159
      at baseline to 490 +/- 275 microg/l at the end of the study, but iron,
      transferrin levels and transferrin saturation did not change. The haemoglobin
      level remained stable (12 +/- 1.1 at baseline and 12.1 +/- 1.5 g/dl at the end of
      the study). The mean dose of darbepoetin alfa could be reduced from 0.75 to 0.46
      microg/kg/week; epoetin alfa was decreased from 101 to 74 IU/kg/week; and the
      mean dose of epoetin beta could be reduced from 148 to 131 IU/kg/week at the end
      of treatment. CONCLUSIONS: A regular 50 mg weekly dosing schedule of iron sucrose
      maintains stable iron stores and haemoglobin levels in haemodialysed patients and
      allows considerable dose reductions for epoetins. Low-dose intravenous iron
      therapy may represent an optimal approach to treat the continuous loss of iron in
      dialysis patients.

PMID- 16891649
TI  - Mini-incision for strictly retroperitoneal nephrectomy in living kidney donation
      vs flank incision.
AB  - BACKGROUND: Mini-incision donor nephrectomies (MIDNs) were established during the
      last decade, as an alternative to traditional open donor nephrectomy (ODN) via
      flank incision. In this study, we investigated intra-operative and post-operative
      data on outcome following MIDN in comparison with ODN data. METHODS: Data of 70
      living kidney donations, performed at the University of Regensburg Medical Center
      since 1996, were evaluated. Donor operation was performed as either strictly
      retroperitoneal MIDN (n = 34) or as traditional ODN (n = 36) via flank incision.
      Total operation time, warm ischaemia time (WIT), perioperative pain-medication
      usage and creatinine levels as well as length of hospital stay, return to
      complete enteral nutrition and regular digestion were evaluated retrospectively.
      RESULTS: Total operation times were similar in MIDN, n = 34 (132 +/- 26 min) and
      in ODN, n = 36 (140 +/- 37 min) (P = 0.424). WIT was also similar in both: MIDN
      (0.9 +/- 0.4 min) and ODN (0.9 +/- 0.4 min) (P = 0.568). The requirement for post
      operative opioids in morphine equivalent doses was significantly lower in MIDN
      (8.4 +/- 16 mg) compared with ODN (44 +/- 57 mg) (P = 0.001). Additional
      application of non-opioids (metamizole) (MIDN: 4.8 +/- 6.3 g, ODN: 3.4 +/- 3.9 g)
      and non-steroidal antirheumatic (NSAR) (diclofenac) (MIDN: 322 +/- 361 mg, ODN:
      247 +/- 474 mg) revealed no significant differences between the groups. The
      hospital stay was 4.9 +/- 1.4 days in MIDN which was significantly shorter than
      that in ODN (9.3 +/- 3.3 days) (P = 0.001). Patients achieved fully independent
      mobility earlier in MIDN than in ODN (P = 0.934). Start of enteral nutrition with
      fluids was significantly quicker in MIDN (1.9 +/- 7 h) compared with ODN (12 +/-
      13 h) (P = 0.05). Full enteral nutrition was accomplished significantly earlier
      in MIDN (1.6 +/- 0.8 days) (P = 0.023). Return to normal digestion revealed no
      significant differences between groups. Serum creatinine levels of all kidney
      donors were in the normal range (66 +/- 18 micromol/l) one day before
      nephrectomy, increased on day 1 after surgery (119 micromol/l +/- 31 micromol/l)
      and were stable on day 3 (115 micromol/l +/- 30 micromol/l) without significant
      differences. CONCLUSION: Strictly, retroperitoneal MIDN in living kidney donation
      is a fast and safe method for the procurement of a living donor graft, giving the
      patient a significantly shorter period of recovery, and thus is an attractive and
      recommendable alternative to traditional ODN procedures.

PMID- 16891650
TI  - Crescentic glomerulonephritis and malignancy--guilty or guilt by association?

PMID- 16891652
TI  - Efficient treatment of crescentric glomerulonephritis associated with hepatitis B
      virus with lamivudin in a case referred with acute renal failure.

PMID- 16891651
TI  - Effectiveness of weekly darbepoetin alfa in the treatment of anaemia of HIV
      infected haemodialysis patients.
AB  - BACKGROUND: Anaemia is aggravated by the coexistence of chronic kidney disease
      (CKD) in patients infected with human immunodeficiency virus (HIV). Darbepoetin
      alfa effectively alleviates CKD-associated anaemia with less frequent dosing than
      recombinant human erythropoietin (EPO). The current study aimed to determine the
      efficacy, safety and cost-effectiveness of darbepoetin alfa compared with
      erythropoietin alfa (EPO-alfa) for treatment of anaemia in HIV-infected subjects
      receiving haemodialysis. METHODS: An open label, single arm, prospective study of
      12 haemodialysis subjects with HIV infection was conducted for a duration of 6
      months after switching from intravenous (i.v.) EPO-alfa two/three times weekly to
      i.v. darbepoetin alfa once weekly. The primary end point was the proportion of
      patients maintaining haemoglobin (Hb) levels>or=11 g/dl while a weekly dose of
      darbepoetin alfa was a secondary end point. RESULTS: Darbepoetin alfa, as
      effectively as EPO-alfa maintained the proportion of the subjects having Hb
      levels>or=11 g/dl at an average weekly dose of 40.60 microg compared with an
      equivalent dose of 51.84 microg for EPO-alfa. Antiretroviral therapy and HIV
      infection stage remained the same for each specific patient throughout the study
      period, including the last 6 months of EPO-alfa therapy. No difference in the
      incidence of adverse effects was observed after switching from EPO-alfa to
      darbepoietin alfa. CONCLUSIONS: Lower doses of darbepoetin alfa at extended
      dosing interval is as safe and effective as EPO-alfa for treating anaemia,
      suggesting that darbepoetin alfa is a more cost-effective therapeutic alternative
      to EPO-alfa in the management of anaemia associated with HIV infection in
      subjects receiving haemodialysis.

PMID- 16891653
TI  - Genetic association analysis of LRCH1 as an osteoarthritis susceptibility locus.
AB  - OBJECTIVE: A genetic association with knee osteoarthritis (OA) of a single
      nucleotide polymorphism (SNP) in intron 1 of the LRCH1 gene was recently reported
      in a UK Caucasian case-control sample and confirmed in a Newfoundland Caucasian
      sample. Our objective was to assess whether the SNP was associated with OA in our
      large UK Caucasian sample. METHODS: The SNP was genotyped in 1521 cases that had
      undergone elective joint replacement of the hip (1098 cases), of the knee (340
      cases) or of the hip and knee (83 cases) due to end-stage primary OA. The SNP was
      also genotyped in 736 controls of similar ages in the cases. RESULTS: There was
      no significant difference (all P-values >0.05) in genotype or allele frequencies
      between our cases and our controls. There was also no significant difference when
      the cases were stratified by sex, by joint replaced or by sex combined with joint
      replaced. CONCLUSION: Our data on 2257 individuals implies that the LRCH1 intron
      1 SNP is not a risk factor for OA aetiology of the knee or of the hip in our UK
      Caucasian sample.

PMID- 16891654
TI  - Impaired endothelial function in patients with ankylosing spondylitis.

PMID- 16891655
TI  - Lack of bone stiffness/strength contribution to osteoarthritis--evidence for
      primary role of cartilage damage.
AB  - OBJECTIVES: This study was performed to assess osseous contributions to
      osteoarthritis, obviating the analysis challenges presented by confounding
      factors in humans and rarity of osteoarthritis in free-ranging mammals. METHODS:
      Frequency of osteoarthritis in 21 bird species was examined and contrasted with
      measures of afflicted element bone stiffness and strength and compression/tension
      resistant characteristics. RESULTS: Osteoarthritis was present in the ankle of 0
      16% of bird species analysed, independent of bone laminarity, cortical thickness,
      circularity, polarization, cross-sectional diameter, length and pneumatization.
      CONCLUSIONS: No correlation of frequency of osteoarthritis with parameters of
      bone strength and biomechanical parameters was found, suggesting that bone is
      only secondarily affected in osteoarthritis and that cartilage is the initial
      target of the disease.

PMID- 16891656
TI  - Parotid gland biopsy compared with labial biopsy in the diagnosis of patients
      with primary Sjogren's syndrome.
AB  - OBJECTIVE: To assess the value of the parotid biopsy as a diagnostic tool for
      primary Sjogren's syndrome (pSS), and to compare the parotid biopsy and the
      labial biopsy with regard to diagnostic value and biopsy-related morbidity.
      METHODS: In 15 consecutive patients with pSS and 20 controls, the parotid biopsy
      was assessed as a diagnostic tool based on the presence of lymphocytic foci,
      benign lymphoepithelial lesions and lymphoid follicles. These new histological
      criteria were compared with established diagnostic criteria for the labial biopsy
      in 35 consecutive patients suspected for pSS who underwent simultaneous biopsies
      from both sites. In addition, both biopsies were compared for morbidity. RESULTS:
      The first analysis revealed a focus score of >or=1 or lymphocytic infiltrates
      (not fulfilling the criterion of a focus score of 1) combined with benign
      lymphoepithelial lesions as diagnostic criteria for pSS. When comparing the
      parotid biopsy with the labial biopsy sensitivity and specificity were comparable
      (sensitivity 78%, specificity 86%). Level of pain was comparable and no loss of
      motor function was observed. No permanent sensory loss was observed after parotid
      biopsy, while labial biopsy led to permanent sensory loss in 6% of the patients.
      Malignant lymphoma was detected in one parotid biopsy by chance, without
      involvement of the labial salivary gland. CONCLUSION: A parotid biopsy has a
      diagnostic potential comparable with that of a labial biopsy in the diagnosis of
      pSS, and may be associated with less morbidity.

PMID- 16891657
TI  - Excitation-contraction coupling in airway smooth muscle.
AB  - Excitation-contraction (EC) coupling in striated muscles is mediated by the
      cardiac or skeletal muscle isoform of voltage-dependent L-type Ca(2+) channel
      (Ca(v)1.2 and Ca(v)1.1, respectively) that senses a depolarization of the cell
      membrane, and in response, activates its corresponding isoform of intracellular
      Ca(2+) release channel/ryanodine receptor (RyR) to release stored Ca(2+), thereby
      initiating muscle contraction. Specifically, in cardiac muscle following cell
      membrane depolarization, Ca(v)1.2 activates cardiac RyR (RyR2) through an influx
      of extracellular Ca(2+). In contrast, in skeletal muscle, Ca(v)1.1 activates
      skeletal muscle RyR (RyR1) through a direct physical coupling that negates the
      need for extracellular Ca(2+). Since airway smooth muscle (ASM) expresses
      Ca(v)1.2 and all three RyR isoforms, we examined whether a cardiac muscle type of
      EC coupling also mediates contraction in this tissue. We found that the sustained
      contractions of rat ASM preparations induced by depolarization with KCl were
      indeed partially reversed ( approximately 40%) by 200 mum ryanodine, thus
      indicating a functional coupling of L-type channels and RyRs in ASM. However, KCl
      still caused transient ASM contractions and stored Ca(2+) release in cultured ASM
      cells without extracellular Ca(2+). Further analyses of rat ASM indicated that
      this tissue expresses as many as four L-type channel isoforms, including
      Ca(v)1.1. Moreover, Ca(v)1.1 and RyR1 in rat ASM cells have a similar
      distribution near the cell membrane in rat ASM cells and thus may be directly
      coupled as in skeletal muscle. Collectively, our data implicate that EC-coupling
      mechanisms in striated muscles may also broadly transduce diverse smooth muscle
      functions.

PMID- 16891658
TI  - Functional characterization of a GJA1 frameshift mutation causing
      oculodentodigital dysplasia and palmoplantar keratoderma.
AB  - A frameshift mutation generated from a dinucleotide deletion (780-781del) in the
      GJA1 gene encoding Cx43 results in a frameshift yielding 46 aberrant amino acids
      after residue 259 and a shortened protein of 305 residues compared with the 382
      in wild-type Cx43. This frameshift mutant (fs260) causes oculodentodigital
      dysplasia (ODDD) that includes the added condition of palmoplantar keratoderma.
      When expressed in a variety of cell lines, the fs260 mutant was typically
      localized to the endoplasmic reticulum and other intracellular compartments. The
      fs260 mutant, but not the G138R ODDD-linked Cx43 mutant or a Cx43 mutant
      truncated at residue 259 (T259), reduced the number of apparent gap junction
      plaques formed from endogenous Cx43 in normal rat kidney cells or keratinocytes.
      Interestingly, mutation of a putative FF endoplasmic reticulum retention motif
      encoded within the 46 aberrant amino acid domain failed to restore efficient
      assembly of the fs260 mutant into gap junctions. Dual whole cell patch-clamp
      recording revealed that fs260-expressing N2A cells exerted severely reduced
      electrical coupling in comparison to wild-type Cx43 or the T259 mutant, whereas
      single patch capacitance recordings showed that fs260 could also dominantly
      inhibit the function of wild-type Cx43. Co-expression studies further revealed
      that the dominant negative effect of fs260 on wild-type Cx43 was dose-dependent,
      and at a predicted 1:1 expression ratio the fs260 mutant reduced wild-type Cx43
      mediated gap junctional conductance by over 60%. These results suggest that the
      46 aberrant amino acid residues associated with the frameshift mutant are, at
      least in part, responsible for the manifestation of palmoplantar keratoderma
      symptoms.

PMID- 16891659
TI  - Insights into allosteric control of vinculin function from its large scale
      conformational dynamics.
AB  - Vinculin is an important constituent of both cell-cell and cell-matrix junctions,
      where it plays crucial roles in the regulation of cell adhesion and migration.
      When activated, it mediates the linkage between cadherins (cell-cell) or
      integrins (cell-matrix) and the actin cytoskeleton through interactions with
      various proteins. The activation of vinculin requires structural conversions from
      an autoinhibited conformation to the "open" conformations in which the occluded
      binding sites of its different ligands become exposed, while the structural
      dynamics underlying the vinculin activation remains largely unknown. Here we
      report the first computational study of large scale conformational dynamics of
      full-length vinculin. We find that the "holding" and "releasing" motions between
      vinculin tail and pincer-like structure formed by first three domains of vinculin
      are the dominant motions near the native state of vinculin, indicating that an
      inherent flexibility of vinculin has a large influence on its allostery. We also
      find a cooperative dissociation between the head and tail domains of vinculin
      with increasing temperature in both thermodynamic and kinetic simulations,
      implying that vinculin may function as an allosteric switch in response to
      external signals. We show that the kinetics of vinculin unfolding exhibits
      specific sequential patterns, suggesting that a sophisticated interplay between
      domains may synergistically contribute to vinculin activation. We further find
      that the interaction between vinculin-binding site peptide from talin and
      vinculin significantly destabilizes the intramolecular head-tail interactions,
      suggesting a direct role of talin binding in vinculin activation.

PMID- 16891660
TI  - Requirement of protein kinase D tyrosine phosphorylation for VEGF-A165-induced
      angiogenesis through its interaction and regulation of phospholipase Cgamma
      phosphorylation.
AB  - Vascular endothelial cell growth factor-A(165) (VEGF-A(165)) is critical for
      angiogenesis. Although protein kinase C-mediated protein kinase D(PKD)activation
      was implicated in the response, the detailed mechanism remains unclear. In this
      study, we found that VEGF-A(165)-stimulated tyrosine phosphorylation of PKD and
      the dominant negative mutant of PKD, PKD(Y463F), inhibited VEGF-A(165)-induced
      human umbilical vein endothelial cell (HUVEC) proliferation. In addition,
      PKD(S738A/S742A) overexpression inhibited VEGF-induced HUVEC migration.
      Furthermore, knockdown of PKD by its specific small interfering RNA inhibited
      VEGF-induced HUVEC proliferation and migration. Moreover transfection of
      PKD(Y463F), PKD(S738A/S742A), or PKD-small interfering RNA blocked VEGF-induced
      angiogenesis in vivo. Our signaling experiments show that KDR not Flt-1 mediated
      PKD tyrosine phosphorylation and KDR tyrosine residues 951 and 1059 were required
      for VEGF-A(165)-stimulated PKD serine and tyrosine phosphorylation, respectively.
      Whereas G protein Gbetagamma subunits were required for both PKD serine
      phosphorylation and tyrosine phosphorylation, intracellular Ca(2+) mobilization
      was required for VEGF-A(165)-stimulated PKD tyrosine phosphorylation and
      phospholipase C (PLC) activity was required for PKD serine phosphorylation.
      Surprisingly, the PLC inhibitor did not inhibit PKD tyrosine phosphorylation.
      Instead, PKD tyrosine 463 was required for VEGF-A(165)-stimulated PLCgamma
      tyrosine phosphorylation. Moreover, PKD interacted with PLCgamma even in
      unstimulated cells, and PKD tyrosine 463 phosphorylation was not required for
      this interaction. Together, we demonstrate that PKD interacts with PLCgamma and
      becomes tyrosine phosphorylated upon VEGF stimulation, leading to PLCgamma
      activation and angiogenic response of VEGF-A(165).

PMID- 16891662
TI  - Optimization of an innovative hollow-fiber process to produce lactose-reduced
      skim milk.
AB  - The research field for applications of lactose hydrolysis has been investigated
      for several decades. Lactose intolerance, improvement for technical processing of
      solutions containing lactose, and utilization of lactose in whey are the main
      topics for development of biotechnological processes. We report here the
      optimization of a hollow-fiber membrane reactor process for enzymatic lactose
      hydrolysis. Lactase was circulated abluminally during luminal flow of skim milk.
      The main problem, the growth of microorganisms in the enzyme solution, was
      minimized by sterile filtration, ultraviolet irradiation, and temperature
      adjustment. Based on previous experiments at 23 +/- 2 degrees C, further
      characterization was carried out at 8 +/- 2 degrees C, 15 +/- 2 degrees C (beta
      galactosidase), and 58 +/- 2 degrees C (thermostable beta-glycosidase) varying
      enzyme activity and flow rates. For a cost-effective process, the parameters 15
      +/- 2 degrees C, 240 U/mL of beta-galactosidase, an enzyme solution flow rate of
      25 L/h, and a skim milk flow rate of about 9 L/h should be used in order to
      achieve an aimed productivity of 360 g/(L x h) and to run at conditions for the
      highest process long-term stability.

PMID- 16891661
TI  - Dual roles of tight junction-associated protein, zonula occludens-1, in
      sphingosine 1-phosphate-mediated endothelial chemotaxis and barrier integrity.
AB  - In this report, sphingosine-1-phosphate (S1P), a serum-borne bioactive lipid, is
      shown to activate tight-junction-associated protein Zonula Occludens-1 (ZO-1),
      which in turn plays a critical role in regulating endothelial chemotaxis and
      barrier integrity. After S1P stimulation, ZO-1 was redistributed to the
      lamellipodia and cell-cell junctions via the S1P1/G(i)/Akt/Rac pathway.
      Similarly, both endothelial barrier integrity and cell motility were
      significantly enhanced in S1P-treated cells through the G(i)/Akt/Rac pathway.
      Importantly, S1P-enhanced barrier integrity and cell migration were abrogated in
      ZO-1 knockdown cells, indicating ZO-1 is functionally indispensable for these
      processes. To investigate the underlying mechanisms, we demonstrated that
      cortactin plays a critical role in S1P-induced ZO-1 redistribution to the
      lamellipodia. In addition, S1P significantly induced the formation of endothelial
      tight junctions. ZO-1 and alpha-catenin polypeptides were colocalized in S1P
      induced junctional structures; whereas, cortactin was not observed in these
      regions. Together, these results suggest that S1P induces the formation of two
      distinct ZO-1 complexes to regulate two different endothelial functions: ZO
      1/cortactin complexes to regulate chemotactic response and ZO-1/alpha-catenin
      complexes to regulate endothelial barrier integrity. The concerted operation of
      these two ZO-1 complexes may coordinate two important S1P-mediated functions,
      i.e. migration and barrier integrity, in vascular endothelial cells.

PMID- 16891663
TI  - Enhancement of acid tolerance in Zymomonas mobilis by a proton-buffering peptide.
AB  - A portion of the cbpA gene from Escherichia coli K-12 encoding a 24 amino acid
      proton-buffering peptide (Pbp) was cloned via the shuttle vector pJB99 into E.
      coli JM105 and subsequently into Zymomonas mobilis CP4. Expression of Pbp was
      confirmed in both JM105 and CP4 by HPLC. Z. mobilis CP4 carrying pJB99-2 (Pbp)
      exhibited increased acid tolerance (p < 0.05) in acidified TSB (HCl [pH 3.0] or
      acetic acid [pH 3.5]), glycine-HCl buffer (pH 3.0), and sodium acetate-acetic
      acid buffer (pH 3.5) in comparison to the parent strain (CP4) and CP4 with pJB99
      (control plasmid). Although the expression of Pbp influenced survival at a low
      pH, the minimum growth pH was unaffected. Growth of Z. mobilis in the presence of
      ampicillin also significantly increased acid tolerance by an unknown mechanism.
      Results from this study demonstrate that the production of a peptide with a high
      proportion of basic amino acids can contribute to protection from low pH and weak
      organic acids such as acetic acid.

PMID- 16891664
TI  - Simultaneous ethanol and cellobiose inhibition of cellulose hydrolysis studied
      with integrated equations assuming constant or variable substrate concentration.
AB  - The integrated forms of the Michaelis-Menten equation assuming variable substrate
      (depletion) or constant substrate concentration were used to study the effect of
      the simultaneous presence of two exoglucanase Cel7A inhibitors (cellobiose and
      ethanol) on the kinetics of cellulose hydrolysis. The kinetic parameters
      obtained, assuming constant substrate (K(m) = 21 mM, Kic = 0.035 mM; K(icl) = 1.5
      x 1,015 mM; k(cat) = 12 h-1) or assuming variable substrate (K(m) = 16 mM, Kic =
      0.037 mM; K(icl) = 5.8 x 1,014 mM; k(cat) = 9 h-1), showed a good similarity
      between these two alternative methodologies and pointed out that both ethanol and
      cellobiose are competitive inhibitors. Nevertheless, ethanol is a very weak
      inhibitor, as shown by the large value estimated for the kinetic constant K(icl).
      In addition, assuming different concentrations of initial accessible substrate
      present in the reaction, both inhibition and velocity constants are at the same
      order of magnitude, which is consistent with the obtained values. The possibility
      of using this kind of methodology to determine kinetic constants in general
      kinetic studies is discussed, and several integrated equations of different
      Michaelis-Menten kinetic models are presented. Also examined is the possibility
      of determining inhibition constants without knowledge of the true accessible
      substrate concentration.

PMID- 16891665
TI  - Effect of lipase immobilization on resolution of (R, S)-2-octanol in nonaqueous
      media using modified ultrastable-Y molecular sieve as support.
AB  - The lipase from Penicillium expansum PED-03 (PEL) was immobilized onto modified
      ultrastable-Y (USY) molecular sieve and the resolution of (R, S)- 2-octanol was
      carried out in a bioreactor in nonaqueous media by the immobilized lipase. It was
      found that the conversion rate, enantiomeric excess (ee) value, and
      enantioselectivity (E) value of the resolution catalyzed by PEL immobilized on
      modified USY molecular sieve were much higher than those of the reaction
      catalyzed by free PEL and PEL immobilized on other supports. Immobilized on
      modified USY molecular sieve, the PEL exhibited obvious activity within a wider
      pH range and at a much higher temperature and showed a markedly enhanced
      stability against thermal inactivation, by which the suitable pH of the buffer
      used for immobilization could be "memorized." The conversion rate of the reaction
      catalyzed by PEL immobilized on modified USY molecular sieve reached 48.84%, with
      excellent enantioselectivity (average E value of eight batches >460) in
      nonaqueous media at "memorial" pH 9.5, 50 degrees C for 24 h, demonstrating a
      good application potential in the production of optically pure (R, S)-2-octanol.

PMID- 16891666
TI  - A comparative study on biosorption characteristics of certain fungi for
      bromophenol blue dye.
AB  - Laboratory investigations of the potential use of dried biomasses of Rhizopus
      stolonifer, Fusarium sp., Geotrichum sp., and Aspergillus fumigatus as
      biosorbents for the removal of bromophenol blue (BPB) dye from aqueous solutions
      were conducted. Kinetics studies indicated that the BPB dye uptake processes can
      be well described by the pseudo-second-order model. The fungal biomasses
      exhibited the highest dye biosorption at pH 2.0. The Langmuir adsorption model
      appears to fit the dye biosorption better than the Freundlich model, with maximum
      dye uptake capacities ranging from 526 to 1,111 mg/g, depending on the biomass
      used.

PMID- 16891667
TI  - Proliferation, viability, and metabolism of human tumor and normal cells cultured
      in microcapsule.
AB  - In this study, we investigated the effect of the microenvironment provided by
      alginate-poly-L-lysine-alginate (APA) microcapsule with liquefied or gelled core
      on the proliferation, viability, and metabolism of human cells, including
      anchorage-dependent MCF-7 breast cancer cells and primary fibroblasts, and
      anchorage-independent K-562 leukemia cells; cells in conventional culture were
      used as control. The growth pattern of cells in microcapsule was examined by
      phase-contrast micrography. The cell viability, proliferation, organization, and
      gene expression were evaluated by 3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyl
      tetrazolium bromide assay, hematoxylin and eosin staining, live/dead staining, 5
      bromo-20-deoxyuridine labeling, and immunohistochemistry, respectively. Cell
      metabolism was determined by measuring glucose and lactate concentrations in
      medium. The results demonstrate that APA microcapsule with liquefied core
      provides a microenvironment for both anchorage-dependent and anchorage
      independent cells to grow into a large cell aggregate and maintain cell viability
      at a constant level for a period of time. In conclusion, cells in APA
      microcapsule are alive and have proliferation potential with lower metabolism
      rate. APA microcapsule may be a useful tool for in vitro tumor cell modeling and
      anticancer drug screening as well as for cancer gene therapy. In addition, it
      lays a solid foundation for the use of microencapsulation in cell culture in
      vitro and cell implantation in vivo.

PMID- 16891668
TI  - Thiol-dependent serine alkaline proteases from Bacillus sp. HR-08 and KR-8102:
      isolation, production, and characterization.
AB  - Two Bacillus sp. strains, HR-08 and KR-8102, isolated from soil of the west and
      north parts of Iran were screened on gelatin agar medium for their ability to
      produce alkaline protease. The enzymes were active in a wide pH range (6.0-11.0)
      and stable in the alkaline range (7.0-12.0). The optimum temperatures for the
      protease from HR-08 and KR-8102 were 65 and 50 degrees C, respectively. The
      irreversible thermoinactivation of HR-08 and KR-8102 proteases showed that the
      stability of HR-08 enzyme was higher than that of KR-8102 and the half-lives of
      these enzymes were 95 and 32 min at 50 degrees C, respectively. In the presence
      of 10 mM Ca(2+), HR-08 retained 100, 90, and 20% of its initial activity after
      heating for 30 min at 50, 60, and 70 degrees C, respectively. Enzymes were
      inhibited by phenylmethylsulfonyl fluoride and iodoacetate. After inhibition by
      iodoacetate, both enzymes were reactivated by dithiothreitol. These data show
      that the enzymes seem to be thiol-dependent serine alkaline proteases. The
      enzymes especially from HR-08 were stable in the presence of H(2)O(2),
      surfactants, and local detergents; their activities were enhanced in the presence
      of 5 mM Fe(2+); and the presence of 5 mM metal ions such as Mg(2+), Cu(2+), and
      Mn(2+) produced almost no effect.

PMID- 16891669
TI  - Methyl jasmonate stimulates jaceosidin and hispidulin production in cell cultures
      of Saussurea medusa.
AB  - Cell cultures of Saussurea medusa produce valuable secondary metabolites, and
      jaceosidin and hispidulin are the major bioactive compounds. In the present
      study, the cultures were challenged by methyl jasmonate (MJ). The highest
      jaceosidin and hispidulin concentrations (65.2 +/- 3.67 mg/L and 12.3 +/- 0.47
      mg/L) were achieved with 5 microM MJ added to 9-d-old subcultures, being 2.2-fold
      and 4.2-fold, respectively, higher than those from controls. The elicitor had
      little influence on cell growth, indicating that the changed biological processes
      did not include alterations in cell division. Furthermore, we observed that the
      activities of phenylalanine ammonia lyase were transiently increased after
      treatment with MJ, which suggests that this elicitor modifies jaceosidin and
      hispidulin production by regulating the phenylpropanoid pathway.

PMID- 16891671
TI  - Toll-like receptors and atherosclerosis: key contributors in disease and health?
AB  - The identification of Toll-like receptors (TLRs) as key patternrecognition
      receptors of innate immunity has opened inquiries into previously unknown disease
      mechanisms. The ability of TLRs to detect a spectrum of pathogen-derived
      molecules defines their importance in innate immunity and provides a mechanistic
      link between infection and disease. Atherosclerosis is a chronic inflammatory
      disease where immune and metabolic factors interact to initiate and propagate
      arterial lesions. An understanding of TLRs in atherosclerosis could clarify the
      etiology of this complex process. Furthermore, the existence of host-derived
      endogenous TLR ligands may implicate TLR involvement in disease mechanisms beyond
      innate immunity, such as a role in homeostatic mechanisms to resolve injury. Our
      current knowledge of TLRs in atherosclerosis is discussed in this review with
      emphasis on experimental studies in atherosclerosis-susceptible mouse models.
      Highlights from studies of TLR involvement in other disease processes have
      demonstrated that TLR-dependent mechanisms probably parallel those found in
      atherosclerosis, some of which could be important in mitigating atherosclerotic
      injury. Finally, an appreciation of the pro- and anti-atherosclerotic mechanisms
      of TLR activation over the entire lifetime of an organism will provide clues to
      the role of TLRs in both health and disease.

PMID- 16891670
TI  - Sexual dimorphism in innate immune responses to infectious organisms.
AB  - Gender has long been known to be a contributory factor in the incidence and
      progression of disorders associated with immune system dysregulation. More
      recently, evidence has accumulated that gender may also play an important role in
      infectious disease susceptibility. In general, females generate more robust and
      potentially protective humoral and cell-mediated immune responses following
      antigenic challenge than their male counterparts. In contrast, males have
      frequently been observed to mount more aggressive and damaging inflammatory
      immune responses to microbial stimuli. In this article we review the evidence for
      sexual dimorphism in innate immune responses to infectious organisms and describe
      our recent studies that may provide a mechanism underlying gender-based
      differences in conditions such as bacterial sepsis.

PMID- 16891673
TI  - IL-17A-producing neutrophil-regulatory Tn lymphocytes.
AB  - The proinflammatory cytokine IL-17A, mainly produced by specialized T cells,
      plays an important homeostatic role in regulating neutrophil production and blood
      neutrophil counts. This review will assemble and discuss the evidence for this
      function of IL-17A-producing cells, which are collectively called neutrophil
      regulatory T cells or Tn cells. IL-17A-producing lymphocytes are most abundant in
      the mesenteric lymph node, where they account for 0.15% of all lymphocytes. About
      60% of the Tn cells are gammadelta T cells, about 25% NKTlike cells, and less
      than 15% are CD4 T cells. These latter cells are also known as T-17 or ThIL-17
      cells, a subset of Tn cells that also plays an important role in autoimmune
      diseases. IL-17A produced by Tn cells regulates the production of G-CSF, which in
      turn promotes the proliferation of promyelocytes and maturation of neutrophils.
      This homeostatic mechanism plays an important role in normal physiology and in
      host defense against bacterial infections. This review is aimed at highlighting
      the important role of IL-17A-producing T cells at the interface between the
      adaptive and innate immune system.

PMID- 16891677
TI  - Randomized controlled trial of compact fluorescent lamp versus standard
      phototherapy for the treatment of neonatal hyperbilirubinemia.
AB  - BACKGROUND: Special blue tube lights of standard length are used in most neonatal
      units to deliver phototherapy. Of late, special blue compact fluorescent lamp
      phototherapy equipments have been introduced in India, which are claimed to be
      better than standard tube lights. AIM: To compare special blue compact
      fluorescent lamp (CFL) phototherapy with special blue standard-length tube lights
      (STL). METHODS: This randomized, controlled trial was conducted in a level III
      NICU. Neonates, otherwise healthy, of gestation greater than 34 weeks with
      hyperbilirubinemia requiring phototherapy, were included. Rh iso-immunized
      babies, those who underwent prior exchange transfusion and whose parents declined
      to consent were excluded. By stratified block randomization, babies were
      allocated to receive phototherapy by CFL or STL. CFL and STL were both special
      blue lights with irradiance maintained above 15 microWatts/nm/cm2. Total serum
      bilirubin (TSB) was measured 12 hourly till phototherapy was stopped or an
      exchange transfusion was done. Temperature and clinical and laboratory parameters
      of dehydration were recorded 12 hourly till 72 hrs. Nursing staff answered an
      objectivized proforma about the disadvantageous effects on nurses. RESULTS: Fifty
      babies were enrolled in each group. Baseline characteristics, causes of jaundice,
      hemolysis, baseline TSB and irradiance were similar in both groups. Mean duration
      of phototherapy (P = 0.98) was similar in both groups. Kaplan-Meier analysis of
      phototherapy duration showed no difference in the survival curves of the 2 groups
      (P = 0.6). Axillary temperature was similar in both groups and no baby was
      dehydrated. Nursing staff reported no significant differences between CFL and STL
      visavis glare hurting the eyes, giddiness and headache. CONCLUSIONS: CFL
      phototherapy has no superiority over STL phototherapy in terms of efficacy and
      adverse effects on the neonate and effects on nursing staff.

PMID- 16891676
TI  - Advances in pediatric growth hormone therapy: IGF-I-based dosing.

PMID- 16891674
TI  - Restoring immune defenses via lymphotoxin signaling: lessons from
      cytomegalovirus.
AB  - Although primary infection with human cytomegalovirus (HCMV), a beta-herpesvirus,
      is widespread and acquired early in life, it rarely causes disease in immune
      competent individuals. However, in immune-compromised patients HCMV infection or
      reactivation invariably leads to serious disease, the effective treatment of
      which remains a difficult clinical problem. Current antiviral therapy is limited
      not only by toxicity but also by the continual emergence of drugresistant
      viruses. The limitations of these current therapeutics provides a strong impetus
      to develop novel approaches that will enhance the host's immune responsiveness
      while at the same time effectively controlling virus replication. Type I
      interferon (IFN) plays a critical role in initiating innate antiviral defenses
      and promoting adaptive responses and lymphotoxin (LT)-alphabeta has recently been
      identified as an essential effector cytokine regulating the induction of type I
      IFN during CMV infection. In particular, CMV infection of immune-compromised mice
      has revealed the immunotherapeutic potential of the lymphotoxin-beta receptor
      (LTbetaR) signaling pathway to restore immune function and provide protection
      from CMV mortality. In this review, we discuss the potential benefits and risks
      associated with LTbetaR-directed immunotherapy for CMV disease and other
      persistent viral infections.

PMID- 16891672
TI  - Chemoattractant receptor signaling and the control of lymphocyte migration.
AB  - This review focuses on mechanisms by which chemoattractant receptors activate
      downstream signaling pathways in lymphocytes. An emphasis is placed on
      heterotrimeric G protein signaling with a discussion of the specific
      heterotrimeric G-proteins involved in lymphocyte chemotaxis and motility and the
      role of regulator of G protein signaling (RGS) proteins in controlling the
      activation of downstream effectors. Also considered are those direct downstream
      effectors known to function in lymphocyte chemotaxis and/or motility. The
      consequences of targeting genes suspected, known, or serendipitously found to be
      involved in chemokine receptor signaling pathways form much of a basis for the
      review. When needed for clarification, reference to studies of chemoattractant
      signaling in model organisms and in neutrophils will be compared and contrasted
      to studies in lymphocytes. Finally, the emergence of tools to image lymphocyte in
      vitro and in vivo will be mentioned as they are increasing helpful for the
      analysis of lymphocyte trafficking and amendable to the study of chemokine
      receptor signaling.

PMID- 16891678
TI  - Growth pattern and skeletal maturation following growth hormone therapy in growth
      hormone deficiency: factors influencing outcome.
AB  - OBJECTIVE: To evaluate pattern of growth and skeletal maturation following growth
      hormone (GH) therapy in children with GH deficiency (GHD) with special emphasis
      on factors influencing outcome. METHODS: Records of ninety-six children (67 boys,
      29 girls) with GHD treated with GH for 2.3 +/-2.1 years were reviewed. RESULTS:
      Height SDS at the end of treatment was significantly higher than that at
      initiation (-3.4 +/- 1.7 versus -4.8 +/-1.6, P < 0.001); it was however lower
      than target height SDS (corrected height SDS (1.8 +/- 1.6, P < 0.001). The
      greatest increase in height SDS was observed during the first two years of
      treatment. Kaplan Meier survival analysis showed that 92%; of all subjects
      achieving end height SDS in the target height range did so within the first two
      years of treatment. Height SDS for bone age increased by 0.7 +/-0.9 during
      treatment (from -2.5 +/- 1.0 to -1.8 +/- 1.5, P < 0.001); the increase was
      however lower compared to that for height SDS for chronological age (P < 0.01)
      suggesting inadvertent skeletal maturation. End height SDS was influenced by
      duration of treatment and corrected height SDS on multivariate analysis.
      CONCLUSION: GH treatment improves growth parameters in GHD; height however still
      remains compromised. Most of the catch-up growth occurs within two years of
      treatment emphasizing the need of optimal treatment during this period.
      Inadvertent skeletal maturation during treatment indicates a need for evaluating
      the role of agents effective in retarding skeletal maturation.

PMID- 16891679
TI  - Atomoxetine.

PMID- 16891680
TI  - Adolescent violence exposure, gender issues and impact.
AB  - Youth violence is a growing problem worldwide. Research on adolescent violence in
      India is limited. Fifteen hundred high school students were investigated to study
      the prevalence and demographic characteristics of witnesses, victims and
      perpetrators of violence and to see the impact of violence exposure on their
      psychosocial adjustments. Sixty nine percent of students had witnessed violence
      in real life and 28% were of serious nature. Media violence exposure was
      universal. The prevalence of victims and perpetrators was 27% and 13%
      respectively. Bullying was prevalent. Male sex was the most important predictive
      risk factor for witnessing and perpetrating violence (P < or = 0.001). Victims
      were predominantly females. Those having exposure to violence had poorer school
      performance and adjustment scores (P < or = 0.05). Thus violence exposure is
      prevalent even in the lives of Indian adolescents and gender differences exist.
      Its impact on their psychosocial adjustments is detrimental. Early identification
      and corrective interventions of these adolescents is vital.

PMID- 16891681
TI  - Nitroglycerine in scorpion sting with decompensated shock.
AB  - This study was designed to examine the effect of nitroglycerine infusion in
      children hospitalized for scorpion sting with severe myocardial dysfunction and
      decompensated shock. Children satisfying the inclusion criteria were started on
      nitroglycerine infusion under hemodynamic monitoring and other supportive
      measures. The effects of nitroglycerine, including improvement in oxygenation and
      decrease in pulmonary congestion and liver size were recorded. Seven out of 11
      children responded well to nitroglycerine therapy and the clinical response was
      evident within 30 to 60 minutes. The first parameter to improve was oxygen
      saturation, followed by an improvement in the blood pressure and respiratory
      rate. Heart rate was the last parameter to improve after nitroglycerine infusion.
      The average duration of nitroglycerine infusion was 25 hours (12 - 36 hours). It
      was seen that the non-survivors had significant tachycardia at admission, and a
      greater need for assisted ventilation compared to the survivors. We conclude that
      nitroglycerine therapy could bring about significant improvement in myocardial
      function and hemodynamic parameters with a potential for improved survival.

PMID- 16891682
TI  - A clinical profile of shock in children in Punjab, India.
AB  - This prospective study was conducted to determine the frequency, etiology, type
      and outcome of shock in hospitalized children in the age group of 1 month to 15
      years. There were 98 cases of shock, constituting 4.3% out of total admissions.
      Mean age was 2.8 +/-3.4 years. Maximum number of patients (39) was seen in
      infancy. Hypovolemic shock due to acute diarrheal disease was the commonest type
      (45.9%) followed by septic, cardiogenic and distributive shock. Compensated stage
      was common in hypovolemic shock (88.9%) whereas majority of patients with septic
      shock (73.5%) presented in decompensated stage. Overall survival was 73.6%. The
      survival rate was best in hypovolemic shock (97.7%;) followed by septic(53.3%)
      and cardiogenic shock(43.7%). Inotropes and ventilatory support were required in
      46% and 23% patients, respectively. Diagnosis and management of shock in
      compensated stage carried better prognosis than in uncompensated shock
      irrespective of the age of the patient.

PMID- 16891683
TI  - Ovarian and uterine ultrasonography in healthy girls between birth to 18 years.
AB  - The aim of our study was to determine the pattern of female reproductive organ
      growth in Indian girls from birth to 18 years of age and to correlate the uterine
      length, mean ovarian volume (MOV) and Fundo Cervical Ratio (FCR) with
      chronological age, bone age and pubertal breast staging. A cross sectional study
      was performed on 218 girls from birth to 18 years of age. Height, weight, stage
      of puberty, X-ray for bone age and transabdominal ultrasounds were performed on
      all girls. Higher chronological age, bone age and increase in breast stage
      significantly predicted higher MOV (P < 0.001) and higher uterine length (P <
      0.001). The MOV, uterine length and FCR are positively correlated with
      chronological age, bone age, height, weight and breast staging. Data from present
      study may be useful in screening cases of precocious puberty and other disorders
      that may need further evaluation.

PMID- 16891684
TI  - Brain stem auditory evoked responses and visual evoked responses in children with
      tubercular meningitis.
AB  - Thirty two patients between 6 months and 14 years of age with tubercular
      meningitis were evaluated for brain stem auditory evoked response (BAER) and
      Visual evoked responses (VER), within 7 days of admission. Absolute latencies and
      interpeak latencies were compared with values obtained from normal children. BAER
      abnormality was found in 56.25% and VER in 28%children, respectively. BAER
      abnormality correlated with Glasgow Coma Scale at admission and discharge, stage
      of meningitis, raised intracranial pressure, seizure activity, and poor outcome.
      VER abnormality correlated with abnormal fundus findings only.

PMID- 16891685
TI  - Dopa-responsive dystonia (Segawa syndrome).
AB  - A 12 year old boy with gradually worsening global developmental delay was
      diagnosed and managed as quadriplegic cerebral palsy since child-hood. Subsequent
      evaluation revealed marked dystonia over spasticity leading to suspicion of
      Segawa syndrome. Dramatic improvement in clinical condition followed after
      therapy with low dose L-Dopa.

PMID- 16891686
TI  - Methylprednisolone therapy in a child with unresolving ARDS.
AB  - We report successful use of methyl-prednisolone in a 21-month old child with ARDS
      that did not improve with conventional therapy. The child improved and could be
      extubated after 10 days of methylprednisolone therapy. Subsequently, the child
      was weaned off supplementary oxygen. Methylprednisolone appeared to be safe and
      effective in a child with unresolving ARDS.

PMID- 16891687
TI  - Neonatal diabetes mellitus.
AB  - Neonatal diabetes mellitus is a rare form of insulin dependent diabetes mellitus
      that present within the first month of life, lasting at least two weeks and
      requiring insulin therapy. Intrauterine growth restriction, failure to thrive,
      fever, dehydration, hyperglycemia and acidosis with or without ketonuria are the
      clinical features of the disease. We report four cases of neonatal diabetes
      mellitus; two of them had a transient course.

PMID- 16891688
TI  - Fibrin glue for persistent pneumothorax in an extremely low birth weight infant.
AB  - Pleurodesis with fibrin glue has been used to treat bronchopleural fistulas and
      persistent air leaks in adults and neonates. We report successful use of fibrin
      glue in an extremely premature infant to seal a pneumothorax that had persisted
      for more than one week despite high-frequency ventilation.

PMID- 16891689
TI  - Lymphangioma circumscriptum of the tongue.

PMID- 16891690
TI  - Neonatal vallecular cyst.

PMID- 16891691
TI  - Congenital varicella syndrome: presenting with eye complications.

PMID- 16891692
TI  - High Urinary N-acetyl-beta-D-glucosaminidase activity and normal calciuria in
      children with nocturnal enuresis.

PMID- 16891693
TI  - Failure of breastfeeding-need to reappraise antenatal counseling.

PMID- 16891694
TI  - Posterior reversible encephalopathy syndrome (PRES).

PMID- 16891696
TI  - Redetermination of the lanthanum iron sulfide La52Fe12S90.

PMID- 16891695
TI  - A new synthetic cobalt tellurate: Co3TeO6.

PMID- 16891697
TI  - Propynylferrocene and (phenylethynyl)ferrocene.

PMID- 16891698
TI  - Tris(ethylenediamine)nickel(II) bis[2-cyano-2
      (oxidoimino)acetamidato]nickelate(II) monohydrate.

PMID- 16891699
TI  - Poly[[[bis(N,N'-dimethylformamide)zinc(II)]-mu3-5-hydroxybenzene-1,3
      dicarboxylato] toluene hemisolvate].

PMID- 16891700
TI  - Hexakis[tris(ethylenediamine-kappa2N,N')nickel(II)] tricyanocuprate(I) bis{mu
      cyano-bis[tricyanocuprate(I)]} nonahydrate.

PMID- 16891701
TI  - Red and yellow solvates of chloro(2,2':6',2''-terpyridine)platinum(II) chloride
      and Pt...Pt interactions.

PMID- 16891703
TI  - A mu-chloro-bridged dinuclear ruthenium complex with 9H-carbazole: the formation
      of one-dimensional linear chains of star-shaped edge-fused rings.

PMID- 16891702
TI  - Poly[[aquatetraimidazoledi-mu-phthalato-dicopper(II)] monohydrate].

PMID- 16891704
TI  - Bis(3-aminopyridine-kappaN)(4,4'-dimethyl-2,2'-bipyridine-kappa2N,N')(perchlorato
      kappaO)copper(II) perchlorate.

PMID- 16891705
TI  - trans-Aquachloro[(1R,4R,8S,11S)-6,13-diammonio-6,13-dimethyl-1,4,8,11
      tetraazacyclotetradecane-kappa4N(1,4,8,11)]nickel(II) trichloride trihydrate.

PMID- 16891706
TI  - Bis(iminodiethylenediammonium) di-mu5-hydrogenphosphato-pentamolybdate(VI)
      tetrahydrate.

PMID- 16891707
TI  - (4-Bromo-2-formylphenolato)perchlorato(1,10-phenanthroline)copper(II).

PMID- 16891708
TI  - {4,10-Bis[2-(2-oxidobenzylideneamino-kappa2N,O)benzyl]-1,7-dioxa-4,10
      diazacyclododecane-kappa4O1,N4,O3,N10}ytterbium(III) perchlorate acetonitrile
      solvate.

PMID- 16891709
TI  - A lithium ethylenediphosphonate containing lithium chains and symmetric hydrogen
      bonds.

PMID- 16891710
TI  - A polymeric solvent-free variant of a hydridomagnesium inverse crown.

PMID- 16891711
TI  - A long Nb=O double bond in bis(pyridinium) tetrachlorooxo(pyridine
      kappaN)niobate(V) chloride.

PMID- 16891712
TI  - Poly[(2,2'-bipyridine-kappa2N,N')(mu2-dihydrogen phosphato-kappa2O:O')(mu2
      hydrogen phosphato-kappa2O:O')aluminium(III)], Al(2,2'-bipy)(HPO4)(H2PO4), a
      layered inorganic-organic hybrid material.

PMID- 16891713
TI  - Unusual O-coordination of caffeine in tetrakis(mu-3,5-dinitrobenzoato
      kappa2O:O')bis[(caffeine-kappaO)copper(II)].

PMID- 16891714
TI  - (2S,4S,S(Fc))-2-[2-(diphenylthiophosphinoyl)ferrocenyl]-4-methoxymethyl-1,3
      dioxane.

PMID- 16891715
TI  - Methyl 4-O-benzoyl-2,3-O-isopropylidene-alpha-L-rhamnopyranoside.

PMID- 16891716
TI  - Brucinium 3,5-dinitrobenzoate methanol solvate, methanol disolvate and
      trihydrate.

PMID- 16891717
TI  - Two modifications of L-alanyl-L-tyrosyl-L-alanine with different solvent
      molecules in the crystal lattice.

PMID- 16891718
TI  - Hydrated forms of N-[(3R)-3-(4-methyl-3,5-dioxo-1,2,4-triazolidin-1-yl)-2
      methylenebutanoyl]-(1S,2R)-bornane-10,2-sultam and its enantiomer.

PMID- 16891719
TI  - 4-(2,4-Dinitrophenylsulfanyl)morpholine.

PMID- 16891720
TI  - 2,3,4,5,6-Pentanitroaniline 1,2-dichloroethane disolvate: 'push-pull' deformation
      of aromatic rings by intramolecular charge transfer.

PMID- 16891721
TI  - 4-(4-Chlorobenzylideneamino)-1,5-dimethyl-2-phenyl-1H-pyrazol-3(2H)-one and 4-(2
      chlorobenzylideneamino)-1,5-dimethyl-2-phenyl-1H-pyrazol-3(2H)-one.

PMID- 16891722
TI  - The anilinium chloride adduct of 4-bromo-N-phenylbenzenesulfonamide.

PMID- 16891723
TI  - Beta-lapachone.

PMID- 16891724
TI  - 1-(Isopropylideneamino)guanidinium 2-nitrobenzoate: formation of corrugated
      sheets from R(2)2(8) and R(6)4(16) rings.

PMID- 16891725
TI  - Moxifloxacinium chloride-water-methanol (2/1/1), a novel antibacterial agent.

PMID- 16891726
TI  - (Z)-6-{[1,3-Dihydroxy-2-(hydroxymethyl)propan-2-ylamino]methylene}-2-methoxy-4
      [(E)-o-tolyldiazenyl]cyclohexa-2,4-dienone.

PMID- 16891727
TI  - 2-Hydroxyacetophenone 4-phenylthiosemicarbazone.

PMID- 16891729
TI  - The 2:1 cocrystal of benzamide and pentafluorobenzoic acid.

PMID- 16891728
TI  - 5-Methylsulfanyl-3H-1,2,3-triazolo[4,5-d]pyrimidin-7(6H)-one (2-methylthio-8
      azaxanthine) monohydrate.

PMID- 16891730
TI  - Chains of edge-fused hydrogen-bonded R(3)3(22) rings in 5,3'-dihydroxy
      3,6,7,4',5'-pentamethoxyflavone.

PMID- 16891731
TI  - 6-(2-Chloroacetamido)hexanoic acid.

PMID- 16891732
TI  - Tetrathiafulvalene revisited.

PMID- 16891733
TI  - 1,4-Bis(triisopropylsilyl)buta-1,3-diyne and 1,4-bis(biphenyl-4-yl)buta-1,3
      diyne.

PMID- 16891734
TI  - 3,5-Dichloro-4-cyanobenzoic acid: two polymorphs and the 0.25-hydrate, exhibiting
      two-dimensional ribbons and nets involving hydrogen-bonding and intermolecular
      Cl...N interactions.

PMID- 16891735
TI  - Anhydrous guanine: a synchrotron study.

PMID- 16891736
TI  - 3-(5-Chloro-3-methyl-1-phenylpyrazol-4-yl)-1,5-diphenylpentane-1,5-dione: sheets
      built from C-H...O and C-H...pi(arene) hydrogen bonds.

PMID- 16891737
TI  - A hydrogen-bonded chain of rings in 7-amino-5-tert-butyl-2-methylpyrazolo[1,5
      a]pyrimidine, and a hydrogen-bonded framework structure in 3,7-diamino-2,5
      dimethylpyrazolo[1,5-a]pyrimidine monohydrate.

PMID- 16891738
TI  - 3-(4-Methoxyphenyl)-7,7-dimethyl-1,6,7,8-tetrahydropyrazolo[3,4-b]quinolin-5-one:
      a chain of centrosymmetric rings built from N-H...N and C-H...pi(arene) hydrogen
      bonds.

PMID- 16891739
TI  - 1,6,11,16-Tetraoxacycloeicosane-2,5,12,15-tetraone.

PMID- 16891740
TI  - Double-helix pattern in a model compound of non-linear optical polymers.

PMID- 16891741
TI  - (R)-N-[(R)-1-(2-Hydroxy-5-methylphenyl)-2-phenylethyl]-2-methyl-1
      phenylpropylammonium chloride.

PMID- 16891743
TI  - Permanent molars: delayed development and eruption.
AB  - Delayed development and eruption of all the permanent molars is a rare
      phenomenon, which can cause disturbance in the developing occlusion. The eruption
      of permanent first and second molars is very important for the coordination of
      facial growth and for providing sufficient occlusal support for undisturbed
      mastication. In the case described, the first permanent molars were delayed in
      their development and were seen erupting at the age of nine and a half years.
      Severe disparity between the left and the right side of the dentition with
      respect to the rate of development of molars were also present.

PMID- 16891742
TI  - Non-syndrome associated multiple supernumerary teeth: a report of two cases.
AB  - Multiple supernumerary teeth are usually associated with syndromes. On the
      contrary, multiple supernumerary teeth without association with any syndromes are
      very rare. This article presents a report of two cases with multiple
      supernumerary teeth not associated with any syndrome and emphasizes the routine
      advice of orthopantomogram whenever a single supernumerary tooth is detected
      irrespective of whether the patient has any syndrome or not.

PMID- 16891744
TI  - Odontoclastoma.
AB  - Case report showing classical odontoclastoma along with in vivo illustrations of
      the affected tooth and intral oral periapical radiograph.

PMID- 16891745
TI  - Supplemental mandibular central incisor.
AB  - Most of the supernumerary teeth are located in anterior maxillary region with
      their presence giving rise to a variety of clinical problems. Occurrence of
      supernumerary supplemental mandibular central incisor is a rare phenomenon. This
      case report describes a rare case of supernumerary supplemental mandibular
      central incisor which had erupted labially causig mild crowding in the anterior
      midline region.

PMID- 16891746
TI  - Incontinentia pigmenti.
AB  - Incontinentia pigmenti or Bloch-Sulzberger syndrome, is a rare X linked dominant
      disorder with characteristic skin, hair, eye, dental and neurological
      abnormalities commonly affecting females. This article reports the clinical
      features and management of a 11 year old girl diagnosed with Incontinentia
      pigmenti.

PMID- 16891747
TI  - Rubinstein Taybi syndrome.
AB  - Rubinstein Taybi syndrome or Broad Thumb and Hallux syndrome is a genetic
      multisystem disorder characterized by facial dysmorphism, growth retardation and
      mental deficiency. A ten-year-old boy who had come to the Department of
      Pedodontics, Ragas Dental College, Chennai, with the chief complaint of
      unaesthetic appearance with extra teeth revealed delay in the developmental
      milestones. The patient appeared to be hyperactive and mentally retarded. Extra
      oral features revealed distinctive facial appearance with a broad fore head,
      hypertelorism, broad nasal bridge and beaked nose. Intra oral features observed
      were talons cusps in the upper central and lateral incisors, mesiodens, carious
      teeth and plaque accumulation. Since the patient was hyper active and mentally
      retarded, the dental treatment was done under GA. The treatment plan and dental
      management of this patient are discussed in this case report.

PMID- 16891748
TI  - Nasopalatine duct cyst.
AB  - Nasopalatine duct cyst is an intraossseous developmental cyst of the midline of
      the anterior palate. Management of a case of nasopalatine duct cyst in a 10 yr
      old male child is reported.

PMID- 16891749
TI  - Coexistent partial anodontia and supernumerary tooth in the mandibular arch: a
      rare case.
AB  - Coexistent partial anodontia and supernumerary tooth in the lower jaw is a very
      uncommon condition. Very few cases have been reported in the literature of this
      condition, etiology of which is still obscure. Presented here is a rare case of
      simultaneous presence of single supernumerary tooth together with missing
      permanent central incisor teeth in the lower jaw without any associated systemic
      condition or syndrome.

PMID- 16891750
TI  - Ankylosis of primary molar along with congenitally missing first permanent molar.
AB  - Ankylosis of primary mandibular molars has been routinely found to be associated
      with various developmental disturbances in permanent dentition such as aplasia of
      the succedaneous tooth, ectopic eruption of the premolar, infraoclusion of the
      ankylosed tooth leading to tipping of the first permanent molar etc. This article
      describes a rare case where there was ankylosis of a mandibular second primary
      molar along with congenitally missing first permanent molar which resulted in the
      transposition of second premolar. Treatment options and prognosis of the case are
      discussed.

PMID- 16891751
TI  - An impacted supplemental premolar in the mandible.
AB  - Supernumerary teeth are rare anomalies of the maxillofacial complex that are more
      common in the maxilla than in the mandible. This article reports a case of an
      impacted supplemental type of supernumerary tooth in the mandibular arch, in the
      left premolar region. The etiology, types and treatment alternatives are
      discussed.

PMID- 16891752
TI  - Dens evaginatus of anterior teeth (talon cusp) associated with other odontogenic
      anomalies.
AB  - Depending on tooth location, usually, dens evaginatus describes an anomaly of
      posterior teeth and talon cusp as an anomaly of anterior teeth. From the
      standpoint of developmental, morphological and histological considerations dens
      evaginatus is a more acceptable term to use and talon cusp should be considered
      as a subset of dens evaginatus. It mostly occurs as an isolated finding rather
      than an integral part of any disorder. Two cases of dens evaginatus along with
      other dental anomalies are reported.

PMID- 16891753
TI  - Osteogenesis imperfecta.
AB  - Osteogenesis imperfecta is an inherited disorder of the connective tissue. The
      extreme bone fragility seen in patients suffering from osteogenesis imperfecta
      pose a series of problems with regard to behavior management and rendering of
      quality dental treatment. Presented here a case of a four year old child
      suffering from osteogenesis imperfecta.

PMID- 16891755
TI  - Aberrant talon cusps: report of two cases.
AB  - Talon cusp is an uncommon anomaly seen both in primary and permanent dentition.
      In most instances they are associated with other clinical problems such as
      occlusal interferences, poor esthetics and caries susceptibility. Management of
      such instances requires a comprehensive knowledge of the clinical entity as well
      as the problems associated with it. Here, we present two cases of talon cusps.

PMID- 16891756
TI  - Effect of blood lactate concentration and the level of oxygen uptake immediately
      before a cycling sprint on neuromuscular activation during repeated cycling
      sprints.
AB  - The purpose of this study was to determine whether neuromuscular activation is
      affected by blood lactate concentration (La) and the level of oxygen uptake
      immediately before a cycling sprint (preVO(2)). The tests consisted of ten
      repeated cycling sprints for 10 sec with 35-sec (RCS(35)) and 350-sec recovery
      periods (RCS(350)). Peak power output (PPO) was not significantly changed despite
      an increase in La concentration up to 12 mmol/L in RCS(350). Mean power frequency
      (MPF) of the power spectrum calculated from a surface electromyogram on the
      vastus lateralis showed a significantly higher level in RCS(350). In RCS(35),
      preVO(2) level and La were higher than those in RCS(350) in the initial stage of
      the RCS and in the last half of the RCS, respectively. Thus, neuromuscular
      activation during exercise with maximal effort is affected by blood lactate
      concentration and the level of oxygen uptake immediately before exercise,
      suggesting a cyclic system between muscle recruitment pattern and muscle
      metabolites.

PMID- 16891757
TI  - New percentage body fat prediction equations for Japanese males.
AB  - Anthropometry is simple, cheap, portable and non-invasive method for the
      assessment of body composition. While the Nagamine and Suzuki body density
      prediction equation has been frequently used to estimate %BF of Japanese, the
      equation was developed more than 40 years ago and its applicability to the
      current Japanese population has not been studied. This study aimed to compare %BF
      results estimated from anthropometry and dual energy X-ray absorptiometry (DXA)
      in order to examine applicability of the Nagamine and Suzuki equation. Body
      composition of 45 Japanese males (age: 24.3+/-5.5 years, stature: 171.6+/-5.8 cm,
      body mass: 62.6+/-7.1 kg, %BF: 15.7+/-5.6%) were assessed using whole-body DXA
      (Hologic QDR-2000) scan and anthropometry using the protocol of the International
      Society for the Advancement of Kinanthropometry (ISAK). From anthropometric
      measurements %BF was calculated using the Nagamine and Suzuki equation. The
      results showed that the Nagamine and Suzuki equation significantly (p<0.05)
      underestimated %BF of Japanese males compared to the DXA results. There was a
      trend towards greater underestimation as the estimated %BF values using DXA
      increased. New %BF prediction equations were proposed from the DXA and
      anthropometry results. Application of the proposed equations may assist in more
      accurate assessment of body fatness in Japanese males living today.

PMID- 16891758
TI  - Effects of daily walking on subjective symptoms, mood and autonomic nervous
      function.
AB  - It is well known that moderate exercise is beneficial to health. However, the
      effects of exercise on subjective symptoms in relation to mood and autonomic
      nervous function have not yet been fully examined. The purpose of this study was
      to investigate the effects of daily walking on subjective symptoms as well as on
      mood and autonomic nervous function in people who take no medication but have
      some general physical complaints. We assessed their symptoms by the Cornell
      Medical Index (CMI), and mood states by a profile of mood states (POMS) and a
      frontal alpha laterality ratio. Autonomic nervous function was evaluated by a
      supine rest basal level, reactivity to orthostatic challenge (physiological
      stimulus) and to a self-programmed videogame (psychophysiological stimulus) of
      heart rate (HR), heart rate variability (HRV), baroreflex sensitivity and blood
      pressure (BP). Repeated measures analysis of variance showed no significant group
      (control and walking group) x time (pre- and post- walking period) interaction of
      CMI scores. In contrast, the A-H sub-scale (anger and hostility) of POMS and
      basal HR significantly decreased after a 4-week walking period in a walking group
      compared to a control group. Negative mood score of POMS reduced, and basal high
      frequency component of HRV and reactivity to orthostatic challenge of baroreflex
      sensitivity increased marginally significantly compared to the control group.
      Multiple regression analysis revealed a significant contribution of A-H to the
      physical score of CMI, which showed a marginally significant reduction after the
      experimental period in the walking group. These results suggest that daily
      walking can improve mood states and shift autonomic balance to parasympathetic
      predominance, and may consequently contribute to the reduction of subjective
      symptoms.

PMID- 16891760
TI  - Proposal for a method of non-restrictive measurement of resting heart rate in a
      lying position.
AB  - Daily monitoring of heart rates is important in health management. Many
      researchers have analysed heart rate variability by using the resting heart rate
      because such an analysis can facilitate the early discovery of a variety of
      illnesses and health conditions. Some problems that arise in measuring heart rate
      are the feeling of confinement. Therefore, we required a system that could
      measure the resting heart rate in a static position in such a way that the
      subject is completely unaware that the measurement is being recorded. We propose
      a non-restrictive measurement method that uses only an acceleration sensor placed
      inside a down quilt. This method is easy for home use. The acceleration sensor
      was placed inside the quilt such that it was positioned opposite to the left-hand
      side of the subject's chest. Six healthy subjects were requested to lie in the
      supine position and were covered with the quilt equipped with the acceleration
      sensor. Mechanical vibrations that resulted from heart activity were carried
      through the quilt to the acceleration sensor. As a result, periodic vibrations
      were measured successfully, and in the six subjects, these vibrations were proved
      to be highly correlated with the R wave of electrocardiograms. The same results
      were obtained even when the subjects were lying in the left lateral position. The
      results indicated that our new method, which used an acceleration sensor placed
      inside a down quilt, was simple and could be used to measure the resting heart
      rate in a lying position.

PMID- 16891759
TI  - Physique, body composition and maximum oxygen consumption of selected soccer
      players of Kunimi High School, Nagasaki, Japan.
AB  - This study evaluates the physical and physiological ability of selected soccer
      players of Kunimi High School in Nagasaki Prefecture, Japan. The Kunimi team is
      famous for its intensive training, and had won the championship of the All Japan
      High School Soccer Tournament six times by 2003. We measured physique, body
      composition, and maximal oxygen uptake of 72 members aged between 16 and 18 years
      old between 1986 and 1994. They consisted of 66 outfield players (12 forward
      players, 23 midfielders, 31 defenders) and 6 goalkeepers. Body density was
      measured by the under-water weighing method, and Brozek's equation was applied to
      calculate percentage body fat (%Fat, %), fat-free mass (FFM, kg), FFM/height
      (FFM/Ht, kg.m(-1)), and FFM index (FFM/Ht(3), kg.m(-3)). The following results
      were obtained: 1. The average of 66 outfield players was 172.7 cm of height, 64.6
      kg of weight, 54.0 cm of girth of thigh, and 90.0 cm of girth of hip, 9.3% of
      %Fat, 58.6 kg of FFM, 33.9 kg.m(-1) of FFM/Ht and 113.8 kg.m(-3) of FFM index.
      The mean vital capacity was 4.25 L and total lung capacity was 5.58 L. The mean
      maximal ventilation was 138.7 L.min(-1), VO(2)max was 3.95 L.min(-1), and
      VO(2)max/Wt was 61.4 ml.kg(-1).min(-1). 2. Goalkeepers were taller and heavier
      than outfielders, and had a smaller mean value of VO(2)max/Wt than outfielders
      (p<0.01). 3. For 23 out of the 72 players measured twice with an interval of
      about one year, FFM increased and %Fat reduced significantly, while V(E)max,
      VO(2)max and VO(2)max/Wt did not change. Kunimi players of the present study had
      as large a VO(2)max/Wt as local players, and a similar or slightly smaller
      VO(2)max/Wt than national-level players. They had similar %Fat and a similar
      VO(2)max/Wt with professional soccer players in England (Davis et al., 1992)
      while they had much smaller physiques.

PMID- 16891761
TI  - Quantitative fluorescence measurement of cardiac Na+/Ca2+ exchanger inhibition by
      kinetic analysis in stably transfected HEK293 cells.
AB  - We developed a method to quantitatively evaluate the potency of Na+/Ca2+
      exchanger (NCX) inhibitors with fluorescence microscopy in NCX1-transfected HEK
      293 cells. The reverse mode and forward mode NCX activities were measured as the
      ascending slope of the early phase increase in cytoplasmic Ca2+ concentration
      after change to low Na+ extracellular solution and the descending rate (inverse
      of the exponential time constant) on return to normal solution, respectively.
      Both modes of NCX were inhibited by SEA0400 (2-[4-[(2,5
      difluorophenyl)methoxy]phenoxy]-5-ethoxyaniline) and KB-R7943 (2-[2-[4-(4
      nitrobenzyloxy)phenyl]ethyl]isothiourea methanesulfonate), and the concentration
      inhibition relationships for both inhibitors were in good agreement with those
      previously reported in voltage clamped cardiomyocytes.

PMID- 16891762
TI  - A late cutaneous response in actively sensitized rats: a new method for
      evaluating the efficacy of antiallergic drugs.
AB  - We established a new and facile model to investigate allergic mechanism and
      assess the effect of antiallergic compounds. Male Wistar rats were actively or
      passively sensitized. Active sensitization was performed by injection of both
      dinitrophenylated-ovalbumin (DNP-OA) and Bordetella pertussis. Nine days later,
      DNP-OA was injected into the right hind footpad. This antigen challenge induced a
      biphasic footpad swelling that consisted of an early-phase (EPR) and a late-phase
      response (LPR). In rats passively sensitized with rat anti-DNP-OA serum, DNP-OA
      induced only EPR. The EPR was suppressed by disodium cromoglycate, a mast cell
      stabilizer, but not by cyclosporin A, an immunosuppressant, while the LPR was
      suppressed by cyclosporin A. Furthermore, to investigate these two allergic
      responses determined by the interactions between the hapten and the carrier
      proteins, two distinct haptenated antigens were created. DNP-Ascaris (DNP-As)
      induced a marked EPR and LPR in DNP-As-sensitized rats. However, DNP-As induced
      only EPR in DNP-OA-sensitized rats, indicating that the usage of the same carrier
      protein in both sensitization and challenge was necessary for induction of LPR.
      These data suggest that this actively sensitization model in which EPR and LPR
      are functionally distinguishable should be useful for evaluating the efficacy of
      antiallergic compounds.

PMID- 16891763
TI  - The effects of HMG-CoA reductase inhibitor on vascular progenitor cells.
AB  - Circulating bone marrow-derived vascular progenitor cells contribute to
      angiogenesis, atherosclerosis, and the response to vascular injury. These
      vascular progenitor cells consist of two cell groups, endothelial progenitor
      cells (EPCs) and smooth muscle progenitor cells (SMPCs). Although HMG-CoA
      reductase inhibitors (statins) have been reported to inhibit atherosclerosis
      partially by increased EPCs, the effects of statins on SMPCs are unclear.
      Therefore, we investigated the relationship between EPCs and SMPCs and whether
      pravastatin has atheroprotective effects on SMPCs. Peripheral mononuclear cells
      (MNCs) were isolated and cultured on fibronectin-coated dishes in SMPC medium.
      MNCs were stained with acetylated low density lipoprotein and lectin, or alpha
      smooth muscle actin, and cell numbers were counted. mRNA expression and vascular
      endothelial growth factor (VEGF) protein synthesis of MNCs were evaluated.
      Pravastatin significantly increased the number of EPC and decreased the number of
      SMPC. mRNA expression of VEGF, endothelial nitric oxide synthase, VEGF receptor-2
      (KDR), and Akt were up-regulated, and VEGF secretion was increased by
      pravastatin. The present study demonstrated that pravastatin has promotive
      effects on the differentiation from MNCs to EPC cells, while inhibitory effects
      to SMPC cells. Our findings suggest a previously unreported mechanism of the
      effect of statin therapy on vascular progenitor cells.

PMID- 16891765
TI  - Potentiation of ethanol in spatial memory deficits induced by some
      benzodiazepines.
AB  - Triazolam caused no significant increase in the total error at 0.05 and 0.1
      mg/kg. However, at 0.2 mg/kg, it caused a significant increase in total error.
      Almost the same findings were observed with brotizolam and rilmazafone. That is,
      at 0.2 and 0.5 mg/kg of brotizolam, 0.5 and 1.0 mg/kg of rilmazafone caused no
      significant increase in the total error. However, brotizolam at 1.0 mg/kg and
      rilmazafone at 2.0 mg/kg caused a significant increase in total error. Triazolam
      (0.05 mg/kg) and ethanol (1.0 g/kg) showed no significant effect on the numbers
      of errors when used alone separately, but the simultaneous use of triazolam and
      ethanol caused a significant increase in total error. Almost the same findings
      were observed with the coadministration of brotizolam (0.2 mg/kg) or rilmazafone
      (0.5 mg/kg) with ethanol. These results clearly indicate that all the short
      acting benzodiazepines used in the study showed potentiation by ethanol in
      spatial memory deficits in mice.

PMID- 16891764
TI  - Protein kinase C beta inhibitor LY333531 attenuates intercellular adhesion
      molecule-1 and monocyte chemotactic protein-1 expression in the kidney in
      diabetic rats.
AB  - In vitro studies have shown that activation of protein kinase C (PKC) is a key
      mediator of intercellular adhesion molecule-1 (ICAM-1) and monocyte
      chemoattractant protein-1 (MCP-1) in a range of cell types and in response to
      high glucose, however, its role in the in vivo setting has not been clearly
      delineated. Streptozotocin-induced diabetic rats were treated with the PKC-beta
      isoform inhibitor LY333531 for 8 weeks. LY333531 treatment significantly
      attenuated increased urinary albumin excretion rate and glomerular volume and
      tubulointerstitial injury index as well as elevated PKC activity and PKC-beta
      protein expression in the kidney. Level of malondialdehyde was markedly higher
      and antioxidant enzyme activity such as superoxide diamutase and catalase as well
      as glutathione peroxidase were significantly lower in the kidney from diabetic
      rats than that of the control group. LY333531 administration could remit these
      changes. Increased macrophages recruitment as well as ICAM-1 and MCP-1 protein
      expression in the kidney were significantly inhibited by LY333531 in diabetic
      rats. It is concluded that mechanism of renoprotection of LY333531 may be
      correlated, at least partly, with suppression of increased macrophages
      recruitment and overexpression of ICAM-1 and MCP-1 in diabetic rats.

PMID- 16891766
TI  - Effects of antiarrhythmic drugs on apoptotic pathways in H9c2 cardiac cells.
AB  - Antiarrhythmic drugs may induce cellular apoptosis in the heart. By using
      representatives of 5 different categories of antiarrhythmic drugs, that is,
      pilsicainide, propranolol, nifekalant, verapamil, and amiodarone, we investigated
      whether these ion channel blockers or beta-antagonists affect cardiac apoptosis
      in cell cultures. Cultured H9c2 cells were treated with the drugs at varying
      concentrations. To determine the degree of apoptosis, the percentage of
      hypodiploid cells, mitochondrial transmembrane potential (DeltaPsi(m)), and
      activities of caspases were measured quantitatively. At 24 h after
      administration, only amiodarone induced apoptosis in the H9c2 cells. Amiodarone
      at a concentration of 14.8 microM or higher decreased DeltaPsi(m) and activated
      caspase-2 within 3 h of administration, and it caused the appearance of
      hypodiploid cells and activation of caspases-3 and -9 at 6 h or later. Thus,
      amiodarone, but none of the other antiarrhythmic drugs tested, possesses a pro
      apoptotic effect, mainly via the mitochondrial pathway, suggesting that this
      effect is distinct from the blocking action of Na+, K+, and Ca2+ channels or the
      beta-adrenergic receptor. Furthermore, induction of apoptosis in a dose-dependent
      manner by amiodarone indicates the importance of monitoring the serum
      concentration in order to avoid its adverse effects.

PMID- 16891767
TI  - The novel hypoglycemic agent YM440 improves hepatic insulin resistance in obese
      Zucker fatty rats.
AB  - The novel hypoglycemic agent YM440 ((Z)-1,4-bis{4-[(3,5-dioxo-1,2,4-oxadiazolidin
      2-yl)methyl] phenoxy}but-2-ene) is a ligand of the peroxisome proliferator
      activated receptor (PPAR) gamma. YM440 has unique pharmacological profiles both
      in vitro and in vivo, but, it is not clear whether the compound has a significant
      effect on hepatic or peripheral insulin response throughout the body. The aim of
      this study is to examine the effects of YM440 on hepatic and peripheral insulin
      resistance in Zucker fatty (ZF) rats using the euglycemic-hyperinsulinaemic clamp
      technique. Treatment of ZF rats with YM440 (300 mg/kg per day) for 2 weeks
      significantly decreased plasma concentrations of glucose and insulin without
      inducing obesity. YM440 caused a 2-fold increase in the glucose infusion rate
      during euglycemic clamping compared with the vehicle control. YM440 also
      decreased the percent change in hepatic glucose production rate caused by
      intravenous insulin infusion in ZF rats. YM440 had no significant effect on the
      glucose disposal rate. These results indicate that YM440 ameliorates hepatic, but
      not peripheral insulin resistance in ZF rats. These findings strongly suggest
      that the main target organ of YM440 is the liver, unlike other PPARgamma agonist.

PMID- 16891768
TI  - Blockade by NIP-142, an antiarrhythmic agent, of carbachol-induced atrial action
      potential shortening and GIRK1/4 channel.
AB  - Mechanisms for the atria-specific action potential-prolonging action of NIP-142
      ((3R*,4S*)-4-cyclopropylamino-3,4-dihydro-2,2-dimethyl-6-(4
      methoxyphenylacetylamino)-7-nitro-2H-1-benzopyran-3-ol), a benzopyran compound
      that terminates experimental atrial arrhythmia, was examined. In isolated guinea
      pig atrial tissue, NIP-142 reversed the shortening of action potential duration
      induced by either carbachol or adenosine. These effects were mimicked by
      tertiapin, but not by E-4031. NIP-142 concentration-dependently blocked the human
      G protein-coupled inwardly rectifying potassium channel current (GIRK1/4 channel
      current) expressed in HEK-293 cells with an EC50 value of 0.64 microM. At higher
      concentrations, NIP-142 blocked the human ether a go-go related gene (HERG)
      channel current with an EC50 value of 44 microM. In isolated guinea-pig papillary
      muscles, NIP-142 had no effect on the negative inotropic effect of carbachol
      under beta-adrenergic stimulation, indicating lack of effect on the muscarinic
      receptor and Gi protein. These results suggest that NIP-142 directly inhibits the
      acetylcholine-activated potassium current.

PMID- 16891769
TI  - First phase of glucose-stimulated insulin secretion from MIN 6 cells does not
      always require extracellular calcium influx.
AB  - To demonstrate an involvement of ATP-sensitive potassium (K(ATP)) channel
      independent pathways in the first phase of glucose-stimulated insulin secretion
      (GSIS) from pancreatic beta cells, the time course of GSIS from MIN6 cells was
      analyzed at 30-s sample intervals. GSIS was biphasic with the first phase being
      observed 120 to 390 s after glucose addition, peaking at 180 s, and with a
      shoulder at 240 to 330 s. Both 10 microM diazoxide and 3 microM verapamil
      completely inhibited tolbutamide- or glibenclamide-induced insulin secretion and
      suppressed the peak of the first phase of GSIS, but did not result in complete
      suppression. The shoulder following the peak was suppressed by 1 muM dantrolene.
      The peak, but not shoulder, disappeared under the extracellular Ca2+-free
      condition. A significant amount of insulin secretion remained even in the
      combined presence of verapamil and dantrolene. The Na+ channel blocker
      tetrodotoxin (30 nM) nearly completely inhibited the first phase release. These
      results suggest that the first phase of GSIS from MIN6 cells depends on both Ca2+
      dependent and -independent mechanisms. The former mechanism includes the
      extracellular Ca2+ influx via L-type voltage-dependent calcium channel and
      intracellular Ca2+ release from endoplasmic reticulum via ryanodine receptors,
      and the latter mechanism involves the pathways associated with Na+ channels.

PMID- 16891770
TI  - Effects of subchronic treatment with selegiline on L-DOPA-induced increase in
      extracellular dopamine level in rat striatum.
AB  - Selegiline is used an adjunct to L-DOPA therapy. We investigated extracellular
      striatal dopamine (DA) level in awake rats treated with L-DOPA and/or selegiline
      using a microdialysis method. Rats given 10 mg/kg, i.p. per day selegiline for 7
      days were administered with a single dose of 100 mg/kg, i.p. L-DOPA 0 (3 h), 1,
      3, 7, 14, 21, or 28 days after the last selegiline treatment. Carbidopa was
      administered 0.5 h before L-DOPA administration. The significant increase in
      basal DA level before L-DOPA treatment persisted until 1 day after the last
      selegiline treatment, and the significant decrease in basal DOPAC level persisted
      for more than 28 days. Thus, selegiline affected DA catabolism for more than 28
      days. Total monoamine oxidase (MAO) and MAO-B activities at day 0 decreased by
      22% and 5.7%, respectively. The significant enhancement of L-DOPA-induced
      increase in DA level was observed until 3 days after the last selegiline
      treatment. Next, the effects of reducing L-DOPA dose by 25% were examined 3 h
      after the last selegiline treatment. A dose-dependent decrease in DA level was
      observed, indicating that DA level in selegiline-treated rats can be controlled
      by L-DOPA dose.

PMID- 16891771
TI  - Disturbance of response to acute thermal pain in naturally occurring
      cholecystokinin-a receptor gene knockout Otsuka Long-Evans Tokushima Fatty
      (OLETF) rats.
AB  - Otsuka Long-Evans Tokushima Fatty (OLETF) rats lack cholecystokinin-A receptor
      (CCK-AR) because of a genetic abnormality. We observed that body temperature
      homeostasis in response to changes in ambient temperature was deteriorated in
      OLETF rats, while the functions of the signal outputs from the hypothalamus to
      effectors were not impaired. Deteriorated homeostasis was also seen in CCK-AR
      deficient (-/-) mice. In the present study, we examined whether the sensory
      pathway involved in transmitting signals about temperature from the skin to the
      brain was impaired in OLETF rats. To elucidate the involvement of CCK-AR
      function, we conducted the same experiment in CCK-AR(-/-) mice. Responses to
      thermal pain were assessed using the Hargreaves' plantar test apparatus.
      Shortening of withdrawal latency was observed in OLETF rats compared to control
      rats, indicating thermal hyperalgesia. Behavioral responses following paw
      withdrawal were disturbed in OLETF rats. The 5-hydroxytryptamine (5-HT) and 5
      hydroxyindole acetic acid contents in the hippocampus and frontal cortex of OLETF
      rats were significantly higher than in those of the controls. CCK-AR(-/-) mice
      did not show any differences from wild-type mice. In conclusion, OLETF rats
      showed thermal hyperalgesia and disturbed responses to thermal pain, and an
      alteration of 5-HT function might have a role in this disturbance.

PMID- 16891772
TI  - Proteomic modification by nitric oxide.
AB  - The role of nitric oxide (NO) in cellular signaling has become one of the most
      rapidly growing areas in biology during the past two decades. As a gas and free
      radical with an unshared electron, nitric oxide participates in various
      biological processes. The interaction between NO and proteins may be roughly
      divided into two categories. In many instances, NO mediates its biological
      effects by activating guanylyl cyclase and elevates intracellular cyclic GMP
      synthesis from GTP. However, the list of cGMP-independent effects of NO is also
      growing at a rapid rate. In this review, the importance and relevance of
      nitrotyrosine formation are stressed. The utilization of intact cell cultures,
      tissues, and cell-free preparations along with the use of pharmacological,
      biochemical, and molecular biological approaches to characterize, purify, and
      reconstitute these NO regulatory pathways could lead to the development of new
      therapies for various pathological conditions that are characterized by
      unbalanced production of NO.

PMID- 16891773
TI  - Functional role of spliced cytoplasmic tails in P2X2-receptor-mediated cellular
      signaling.
AB  - P2X receptors belong to a unique family of ligand-gated channels in terms of
      their molecular architecture, in which the channel subunit has two transmembrane
      alpha-helixes with a large extracellular loop keeping amino- and carboxy-termini
      in the cytoplasm. Post-transcriptional modifications of P2X receptors could
      diversify cellular responsiveness induced by extracellular ATP in anterior
      pituitary cells and other cell types. Recently, we found a spliced variant P2X2
      transcript, termed P2X2e, in mouse pituitary. The P2X2e has a shorter cytoplasmic
      carboxy-terminal tail than those of full-length P2X2a or splice variant P2X2b
      subunits. Although ATP induced rapid responses in all homomeric P2X2 channels,
      the current induced by P2X2e declined significantly faster than those by P2X2a or
      P2X2b. In this article, we summarize functional alterations of P2X2 receptors
      after splicing reactions. Combinations of different P2X2 subunit carboxy-termini
      to form homomeric and heteromeric channels could be a molecular mechanism for
      promoting functional diversities of ATP-induced cellular signals.

PMID- 16891774
TI  - Babesia microti-like parasites detected in Eurasian red squirrels (Sciurus
      vulgaris orientis) in Hokkaido, Japan.
AB  - Six Eurasian red squirrels (Sciurus vulgaris orientis), victims of road traffic
      found during 2002 and 2004 near the Noppro Forest Park in Ebetsu, Hokkaido,
      Japan, were examined for the presence of Babesia parasites. Three of the six
      squirrels exhibited positive signals by nested PCRs targeting both the 18S rRNA
      and beta-tubulin genes. Three squirrels proved to be infected with a B. microti
      like parasite as evidenced by sequencing the amplified DNAs and by the morphology
      of the intraerythrocytic parasites. Genotypically, however, the parasite appeared
      to be of a new type, as it was clearly distinguishable from any of the known
      types that have previously been reported in various wild animals. This is the
      first report showing molecular evidence for the presence of B. microti-like
      parasites in Sciuridae.

PMID- 16891775
TI  - Comparison of the effectiveness of high and low LET radiations for the proportion
      of survivals with liver tumors at every age in (C57BL/6N x C3H/HeN) F1 mice.
AB  - To investigate the late effects of neutrons at the energy below 1 MeV on the
      liver carcinogenesis as a function of age, one-week old mice were exposed to 1.0
      Gy monoenergetic neutrons (0.317, 0.525 and 1.026 MeV) or 137Cs gamma rays.
      Survival and carcinogenesis were examined by 18 months of age. Following
      radiation, tumor incidences in liver, Harderian gland, lung, ovary and pituitary
      gland were compared. The proportion of the lifespan with liver tumors exposed to
      neutrons to that exposed to gamma rays was calculated as a function of age.
      Survival rates among the three groups exposed to neutrons of different energies
      were not significantly different from one another but shorter than those treated
      with gamma rays for both sexes. With regard to liver tumor incidence evaluated at
      18 months of age, the effectiveness of neutrons to gamma rays was 2.54 for
      females, and 2.08 for males by the factor. Levels of estrogen in the serum were
      similar between mice bearing liver tumors and those devoid of tumors. In
      conclusion, all three energies of neutrons induced similar effectiveness with
      respect to liver carcinogenicity. Proportions of the lifespan with liver tumors
      of neutron-exposed to gamma-exposed were shorter in females than males along with
      ages over 12 months. To obtain this factor at every age contributed for the
      evaluation of the biological effectiveness of radiations with the parameter of
      tumor incidence and latency simultaneously.

PMID- 16891776
TI  - Characterization and distribution of an arginine vasotocin receptor in mouse.
AB  - A cDNA, which has a high homology with teleost Platichthys flesus [Arg8]
      vasotocin (AVT) receptor (GenBank: AK033957), was found in mouse genome database.
      Analyses of the deduced amino acid sequence revealed that a cDNA has several
      features of AVT receptor. We tentatively named it as a mouse vasotocin receptor
      (MVTR). A two-electrodes voltage clamp technique was applied to characterize the
      MVTR expressed in Xenopus laevis oocytes. AVT induced Ca2+-dependent Cl- currents
      in Xenopus oocytes injected with MVTR cRNA. On the other hand, [Arg8]
      vasopressin, oxytocin and isotocin did not induce such currents. RT-PCR showed
      that MVTR mRNA was specifically expressed in the brain. In situ hybridization
      analysis demonstrated significant expression of MVTR mRNA in suprachiasmatic
      nucleus, arcuate nucleus and medial habenular nucleus of mouse brain. These
      results suggest that MVTR may mediate a variety of physiological functions in
      mouse.

PMID- 16891777
TI  - Gene expression profile by 2,3,7,8-tetrachlorodibenzo-p-dioxin in the liver of
      wild-type (AhR+/+) and aryl hydrocarbon receptor-deficient (AhR-/-) mice.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is one of the most toxic environmental
      pollutants that cause various biological effects on mammals. The purpose of our
      study was to identify the genes involved in hepatotoxicity and
      hepatocarcinogenesis caused by TCDD. C57BL/6 (AhR+/+, wild type) and B6.129
      AhR<tm1Bra>/J (AhR-/-, knock out) mice were injected i.p. with a single treatment
      of TCDD at the dose of 100 microg/kg body weight. Relative liver weight was
      significantly increased at 72 hr after TCDD treatment without an apparent
      histopathological change in AhR+/+ mice (p<0.05). TCDD treatment also
      significantly increased activity of serum alanine aminotransferase in AhR-/- mice
      (p<0.05). The liver was analyzed for gene expression profiles 72 hr later. As
      compared with AhR-/- mice, the expression of 51 genes (>3-fold) was changed in
      AhR+/+ mice; 28 genes were induced, while 23 genes were repressed. Most of the
      genes were associated with chemotaxis, inflammation, carcinogenesis, acute-phase
      response, immune responses, cell metabolism, cell proliferation, signal
      transduction, and tumor suppression. This study suggests that the microarray
      analysis of genes in the liver of AhR+/+ and AhR-/- mice may help to clarify the
      mechanism of AhR-mediated hepatotoxicity and hepatocarcinogenesis by TCDD.

PMID- 16891778
TI  - Bowel welding technique in dogs and cats using a diode laser: an experimental
      study.
AB  - A laser bowel welding technique for dogs and cats was developed. The bowel was
      pinched using a special clamp having an opening on the body developed for this
      experiment (LW clamp). Using the 2 different types of contact probe (blunt tip:
      Laser Bipolar Dissector (LBD); sharp tip: Super Scalpel Dissector (SSD)), the
      laser passed through the hole in the LW clamp to cut the bowels, while at the
      same time, sealing the cut portion. The results obtained in this study showed
      that the optimum laser output using LBD was 6-10 W in dog and cat ileum, and 8-10
      W in dog and cat colon. Optimum laser output using SSD was 6-8 W in dog ileum, 8
      10 W in dog colon, 10 W in cat ileum and 6-8 W in cat colon. No marked
      differences were observed between ileum and colon when using either LBD or SSD.
      At the same power, burst pressure tended to be slightly higher with LBD than with
      SSD, although there were not significant differences between them.
      Histologically, complete sealing of the welded site was seen. Welding and cutting
      of bowel in dogs and cats was thus confirmed to be possible using the LW clamp in
      combination with LBD or SSD probes under a diode laser output of approximately 8
      W for 50-80 s (400-640 J/cm). Thus, we can expect that this method is applicable
      to clinical veterinary medicine.

PMID- 16891779
TI  - The possible role of the tibial plateau angle for the severity of osteoarthritis
      in dogs with cranial cruciate ligament rupture.
AB  - The purpose of this study was to determine factors correlated with the severity
      of radiographic osteoarthritis (OA) scoring in dogs with cranial cruciate
      ligament rupture (CrCLR). Three radiographs of stifle joints (craniocaudal,
      mediolateral, and mediolateral radiograph with 90 degree flexion of the stifle
      and tarsal joints) were obtained from 36 dogs with CrCLR (Clinical group) and
      from 22 dogs without stifle joint disease (Control group). Information about
      these dogs was collected from the owners and from medical records. Radiographic
      OA scores in each dog in the clinical group were determined from radiographs
      using a numeric grading system previously reported. The tibial plateau angle
      (TPA) in each dog in both groups was measured on mediolateral radiographs with 90
      degree flexion of the stifle and tarsal joints. The Mann-Whitney's U test was
      used for comparing variables between the clinical group and the control group,
      and Spearman's rank correlation test was used for evaluating correlations between
      radiographic OA scores and variables in the clinical group. No significant
      differences were detected between the clinical group and the control group for
      any of the variables. There were two positive correlations; one between the
      radiographic OA score and TPA (r=0.395, p=0.014); and the other between body
      weight and OA score (r=0.399, p=0.013) in the clinical group. Our results
      indicate that body weight and TPA could affect the severity of the radiographic
      OA score in dogs with CrCLR.

PMID- 16891780
TI  - Paragonimus westermani and some rare intestinal trematodes recovered from raccoon
      dogs (Nyctereutes procyonoides viverrinus) introduced recently on Yakushima
      Island, Japan.
AB  - Helminth parasites were collected from 9 raccoon dogs (Nyctereutes procyonoides
      viverrinus) and 2 Japanese weasels (Mustela itatsi sho) on Yakushima Island,
      Japan. The former carnivore was introduced to this World Natural Heritage Area
      presumably within the last two decades, expanding its population thence, although
      detailed process(es) of the introduction is unknown. The collected trematodes
      from raccoon dogs included the triploid form of Paragonimus westermani,
      Brachylaima tokudai, Maritrema eroliae, and Pseudocryptotropa sp. Simultaneously,
      Paragonimus ohirai was found in one weasel killed by a traffic accident. Although
      the triploid form of P. westermani and P. ohirai are known to be distributed in
      some river-mouth areas of Yakushima Island based on previous surveys on crab
      hosts, natural infection was detected for the first time in wild final hosts.
      Particularly, the raccoon dog infected with P. westermani was caught in a
      mountainous area, distant from human residence or river-mouth areas. Although it
      is possible that the infected raccoon dog moved from a river-mouth area endemic
      with P. westermani after infection, the alternative scenario remains to be
      pursued; the endemic area of this zoonosis is expanding along with the recent
      expansion of raccoon dogs or feral cats (Felis catus), that became prevalent
      recently on this island including the mountainous areas. Maritrema eroliae taking
      a variety of shorebirds as its natural final hosts, and a minute trematode,
      Pseudocryptotropa sp., taking unknown natural final host(s) were recorded for the
      first time in raccoon dogs.

PMID- 16891781
TI  - Juvenile bird acanthocephalans recovered incidentally from raccoon dogs
      (Nyctereutes procyonoides viverrinus) on Yakushima Island, Japan.
AB  - Helminth parasites were collected from 14 raccoon dogs (Nyctereutes procyonoides
      viverrinus) and 2 Japanese weasels (Mustela itatsi sho) on Yakushima Island,
      Kagoshima Prefecture (Kyushu), Japan. In addition to trematodes and nematodes
      reported separately, everted cystacanths of 3 bird acanthocephalans
      (Mediorhynchus robustus in 5 animals, Porrorchis leibyi in 2 animals, and
      Sphaerirostris lanceoides in 1 animal) were collected from the raccoon dogs
      introduced recently on this World Natural Heritage Area. A cystacanth of P.
      leibyi was collected also from a weasel indigenous to this island that were
      killed by traffic accidents. Recovery of everted cystacanths of M. robustus from
      the intestine of raccoon dogs was remarkably frequent (36%), suggesting that this
      acanthocephalan should be highly prevalent in passerine hosts on Yakushima
      Island, and the animals might vigorously take insect hosts or paratenic hosts.
      Furthermore, the present report is the second on M. robustus after its first
      record in Japan (Aichi Prefecture, Honshu) as M. garruli from a Eurasian jay
      (Garrulus glandarius japonicus) by Yamaguti in 1939. Porrorchis leibyi has never
      been recorded in Japan.

PMID- 16891782
TI  - Nematodes from raccoon dogs (Nyctereutes procyonoides viverrinus) introduced
      recently on Yakushima Island, Japan.
AB  - Nematodes were collected from 14 raccoon dogs (Nyctereutes procyonoides
      viverrinus) on Yakushima Island, Kagoshima Prefecture (Kyushu), Japan, that were
      the progeny of recently introduced animals to this World Natural Heritage Area,
      probably within the last 2 decades. Seven nematode species (Toxocara tanuki,
      Ancylostoma kusimaense, Arthrostoma miyazakiense, Strongyloides planiceps,
      Trichuris vulpis, Gongylonema sp., and Dirofilaria immitis) were collected from
      the raccoon dogs. Two nematode species (Molineus legerae and Strongyloides
      martis) were collected from 2 Japanese weasels (Mustela itatsi) indigenous to
      this island that were killed by traffic accidents. Considering that foxes and
      other carnivores, except for weasels, dogs and cats, are not distributed on this
      island, most of soil-borne nematodes such as roundworms, hookworms, and
      threadworms in raccoon dogs should have been introduced by the original
      population from the mainland Japan, and the infection hence maintained at a high
      level by new generations. Recovery of the third-stage larvae of Gongylonema sp.
      from the esophagus of raccoon dogs was remarkably frequent (79%), suggesting that
      the animals might vigorously take insect hosts. Although S. martis have never
      been recorded from weasels in Japan until this study, this threadworm might be
      prevalent in a variety of mustelids in Eurasia.

PMID- 16891784
TI  - Parathyroid hormone-related protein (PTHrP) and Ca levels in the milk of
      lactating cows.
AB  - To investigate the roles of mammary PTHrP in calcium uptake and/or release in the
      mammary gland of cows, plasma PTHrP and Ca levels, and their arterial-venous
      differences were examined in a Jersey cow during the periparturient period.
      Levels of Ca in both abdominal aorta and abdominal subcutaneous vein blood
      slightly decreased around the parturition and at 24 days after the parturition,
      however, no remarkable arterial-venous differences were observed. Plasma PTHrP
      levels in both arterial and venous samples were below the detection limit (0.57
      pmol/l) during the experimental period. Milk PTHrP and Ca levels were measured in
      9 Holstein dairy cows. Although plasma PTHrP levels in all arterial and venous
      samples were also below the detection limit, milk PTHrP and Ca levels were
      remarkably high, ranging from 14,900 pmol/l to 41,200 pmol/l and from 772 mg/l to
      1,200 mg/l, respectively. In addition, a significant positive correlation
      (P<0.01) was observed between milk PTHrP and Ca levels. These results suggested
      that mammary PTHrP is closely related to Ca concentration in the milk.

PMID- 16891783
TI  - Identification of Card15/Nod2 mRNA in intestinal tissue of experimentally induced
      colitis in rats.
AB  - Card15/Nod2 has been suggested to be an intracellular pathogen-associated
      molecular pattern (PAMPs) recognition molecule, which contains a leucine-rich
      repeat region similar to the Toll-like receptors (TLRs). Card15/Nod2 gene
      variants play an important role in the susceptibility to Crohn's disease. In this
      study, we examined the kinetics of Card15/Nod2 expression in intestinal tissue
      during inflammation in the 2, 4, 6-trinitrobenzenesulfonic acid (TNBS)-treated
      rat experimental colitis model. At 2 and 4 days after TNBS administration, the
      mononuclear cells remarkably infiltrated the mucosal layer and tunica muscularis,
      which was followed by a gradual decrease to resting levels at 14 days after TNBS
      administration. Card15/Nod2 mRNA expression increased and peaked at 4 days after
      the TNBS administration, followed by a gradual decrease in accordance with the
      amelioration of the inflammatory response. Expressions of Tlr2, Tlr4 and Myd88
      were also upregulated in the inflamed colonic region, and in an in situ
      hybridization study, a positive signal for Card15/Nod2 was observed in the crypt
      of the epithelial cell layer and in the infiltrated cells of the submucosal and
      myenteric regions. These results suggest that in addition to the TLR recognition
      systems, Card15/Nod2 may contribute to the inflammatory process not only in the
      epithelial and submucosal layers but also in the tunica muscularis.

PMID- 16891785
TI  - Inflammatory effect of cleaved bovine lactoferrin by elastase on staphylococcal
      mastitis.
AB  - Elastase activity and concanavalin A (Con A) low affinity bovine lactoferrin
      (bLf) molecule were detected in mammary gland secretions (MGSs) from mammary
      glands (MGs) with clinical staphylococcal mastitis. Changes in clinical symptoms
      correlated with increases in both elastase activity and the concentration of Con
      A low-affinity Lf in MGSs from mastitic MGs. Bovine Lf treated with elastase
      (elastase-Lf) showed various small bLf molecules and the same image on Con A two
      dimensional immunoelectrophoresis as low Con A affinity bLf in MGSs. We confirmed
      the presence of four common bLf peptides for the elastase-bLf and low Con A
      affinity bLf molecules in mastitic MGSs, and synthesized four peptides. Strong
      mRNA expression of interleukin-6 (IL-6), tumor necrosis factor alpha (TNFalpha),
      interleukin-8 (IL-8), and monocyte chemotactic protein-1 (MCP-1) was induced in
      bovine mammary epithelial cells on stimulation with low Con A affinity bLf,
      elastase-bLf, and GQRDLLFKDSAL, a synthesis bLf peptide based on nuclear factor
      kappa B (NFkappaB) activation. These results suggest that bLf was cleaved by
      elastase, and that this cleavage changed the physical function of Lf. Our results
      indicate that elastase induced production of low Con A affinity bLf, including
      the bLf peptide GQRDLLFKDSAL, and had an inflammatory effect on staphylococcal
      mastitis.

PMID- 16891786
TI  - Immunohistochemical distribution of amyloid deposits in 25 cows diagnosed with
      systemic AA amyloidosis.
AB  - The distribution of amyloid deposits was histopathologically and
      immunohistochemically examined in 25 cows aged 5 to 10 years that had been
      diagnosed with systemic AA amyloidosis. This examination revealed that amyloid
      deposits were also present in the hypophysis, ovary, uterus, mammary gland and
      skeletal muscle, in addition to the liver, kidney, spleen, pancreas, thyroid
      gland, adrenal gland, gastrointestinal mucosa, heart, lung and lymph nodes. The
      examined cows tended to have chronic inflammations, including chronic mastitis
      (six cases) or chronic pneumonia (four cases), which is thought of as a causative
      agent of AA amyloidosis. In contrast, five cases did not exhibit any chronic
      inflammation.

PMID- 16891787
TI  - Pulmonary intravascular hemangiosarcoma in a cat.
AB  - A 9-year-old, castrated male Japanese domestic cat presented with a complaint of
      exertional dyspnea. Based on the radiographic findings, presumptive diagnosis of
      aspiration pneumonia or primary diffuse pulmonary neoplasia in the right middle
      lobe was made. Histologically, the pulmonary lesion was characterized by diffuse
      thickening of alveolar wall with the proliferation of apparently atypical
      irregular-shaped cells. Immunohistochemical staining using anti-human factor VIII
      related antigen antiserum showed positive reaction in the cytoplasm of the
      atypical cells. According to the findings, the lesion was diagnosed as pulmonary
      intravascular hemangiosarcoma.

PMID- 16891788
TI  - Pathogenicity of H5N1 influenza A viruses isolated in Vietnam between late 2003
      and 2005.
AB  - Since late 2003, highly pathogenic H5N1 influenza A viruses have spread among
      poultry and wild aquatic birds in Asian countries. Transmission of these viruses
      to humans can be lethal. Most human cases of infection with H5N1 viruses have
      occurred in Vietnam. Therefore, to understand the pathogenicity in mammals of
      these H5N1 viruses, we took viruses isolated from poultry (5 strains) and humans
      (2 strains) in Vietnam and tested their virulence in mice. The results showed
      that the H5N1 viruses from humans were pathogenic in mice and that one avian
      isolate was also pathogenic. These findings suggested that the H5N1 viruses
      circulating in poultry adapted during replication in humans or that strains
      pathogenic in mice were transmitted directly to humans.

PMID- 16891790
TI  - A survey of avian polyomavirus (APV) infection in imported and domestic bred
      psittacine birds in Japan.
AB  - Although birds infected with avian polyomavirus (APV) subclinically could be a
      source of infection, no epidemiological studies of APV in psittacine birds have
      been reported in Japan. In the present study, we investigated subclinical
      morbidity rate of APV in imported and domestically bred psittacine birds by
      polymerase chain reaction (PCR). Of 402 live birds from which blood or feather
      samples were taken between April, 2003 and March, 2004, 11 (2.7%) were found to
      be APV positive. The DNA sequences of the APV t/T antigen region were determined
      for five APV-positive randomly selected samples and were found to be conserved.

PMID- 16891789
TI  - Rhodococcus equi in the soil environment of horses in Inner Mongolia, China.
AB  - Little is known about the distribution of Rhodococcus equi in the soil
      environment of native horses in China. One hundred and eight soil samples were
      collected from native-horse farms in the Hulun Beier grasslands of eastern
      Mongolia, the Xilin Goler grasslands of southern Mongolia, and Tongliao City in
      Inner Mongolia, China. The isolation rates of R. equi from soil samples from the
      Hulun Beier and Xilin Goler grasslands ranged from 25.9% to 30.0%. In contrast,
      isolation rates from soil samples from Tongliao City were as high as 82.3% and
      the mean number of R. equi in soil samples from Tongliao City was 10 times more
      than those of samples from the grasslands. The 488 isolates were examined using
      PCR for the presence of genes that encode virulence-associated 15-17 kDa antigen
      protein (VapA) and the 20 kDa antigen protein (VapB). All isolates were negative
      for virulence-associated proteins. Plasmid profiles of these avirulent isolates
      showed that cryptic plasmids of various sizes were present with an incidence of
      13.3% to 21.5%. The results of the present study contrast with those of our
      recent study (J. Vet. Med. Sci. 67:611-613, 2005), in which we reported that R.
      equi was absent from Mongolian horses in Ulaanbaatar, Mongolia. It is suggested
      that the difference between the results of these two studies is due to the mobile
      pasturing system in Mongolia and nonmobile pasturing system in Inner Mongolia.

PMID- 16891791
TI  - Periorbital cyst with bone defect in a dog.
AB  - A 4-year-old female Miniature Dachshund was referred with a chief complaint of
      right periorbital swelling that had not responded to antibiotic therapy.
      Ultrasonography and fine-needle aspiration revealed that the periorbital lesion
      had a cystic structure without any inflammatory or neoplastic cells. Computed
      tomography (CT) showed that the cyst occupied a defect in the periorbital
      maxillary, lacrimal, and frontal bones and had invaded the nasal cavity. The
      lesion was histologically suspected by incisional biopsy as an epithelial cyst.

PMID- 16891792
TI  - The effect of 7.2% hypertonic saline solution on m-mode echocardiographic indices
      in normovolemic dogs.
AB  - This study investigated whether a small volume of 7.2% hypertonic saline solution
      (HSS) could affect M-mode echocardiographic indices in dogs. HSS induced
      significant increase in heart rate, stroke volume and cardiac index, when the
      fluid infusion was completed (P<0.05). In the HSS group, the left ventricular end
      diastolic volume index, as an index of preload, significantly increased (P<0.05),
      whereas left ventricular end-systolic volume index were not altered. HSS induced
      slight increases in ejection fraction at end of infusion despite significantly
      differences were not observed. In conclusion, HSS did not induce a demonstrable
      effect on M-mode echocardiographic indices of systolic function-enhance cardiac
      contractility, but it caused preload augmentation that may contribute to an
      abrupt and transient increase in cardiac output just after HSS infusion.

PMID- 16891793
TI  - Seroepidemiological evidence for the possible presence of Babesia (Theileria)
      equi and Babesia caballi infections in donkeys in western Xinjiang, China.
AB  - The prevalence of Babesia (Theileria) equi and B. caballi infections in donkeys
      in western Xinjiang China was investigated. In total, 93 serum samples were
      randomly taken from donkeys in the Kashi and Ili areas, and examined for B. equi
      and B. caballi infections by enzyme-linked immunosorbent assays using recombinant
      antigens. Of the 93 samples, 9 (9.6%) and 36 (38.7%) samples were positive for B.
      equi infection and B. caballi infection, respectively. In addition, 2 (2.2%)
      samples were positive for both B. equi and B. caballi infections. These results
      indicate that equine babesiosis might be extensively prevalent in donkeys in
      western Xinjiang.

PMID- 16891794
TI  - Characterization of equid herpesvirus 1 (EHV-1) related viruses from captive
      Grevy's zebra and blackbuck.
AB  - Equid herpes virus 1 (EHV-1) related isolates from a captive blackbuck (strain Ro
      1) and Grevy's zebra (strain T965) behaved similarly to EHV-1 and EHV-9 in
      respect to their host cell range. Restriction enzyme analysis and a phylogenetic
      tree confirmed that Ro-1 and T965 were identical and more closely related to EHV
      1 than to EHV-9. Differences from EHV-1 became obvious firstly, by amino acid
      alignments revealing two unique substitutions in the gB protein of Ro-1 and T965.
      Secondly, an EHV-1 type-specific monoclonal antibody did not detect its antigen
      on Ro-1, T965 or EHV-9 infected cells by immunohistochemistry. The results
      support the view that Ro-1 and T965 isolates represent a distinct, previously
      unrecognized species of equid herpesviruses.

PMID- 16891795
TI  - Expression of CD44 adhesion molecule in rat testis with ischemia/reperfusion
      injury.
AB  - The expression pattern of CD44 was studied in the rat testis following
      ischemia/reperfusion (I/R) injury to elucidate the possible role of the CD44
      adhesion molecule in acute experimental testicular torsion. Western blot analysis
      showed that CD44 expression began to increase significantly 24 hr after
      reperfusion, compared with the normal control; the increased expression persisted
      until 96 hr after I/R. Immunohistochemistry showed that, in the normal testis,
      CD44 was constitutively expressed mainly in ED2-positive resident macrophages in
      the interstitial space. After I/R, the majority of inflammatory cells in the
      interstitial space surrounding the damaged tubules were ED1-positive macrophages
      that were CD44-positive. These findings suggest that the significant increase in
      CD44 expression that occurs during the delayed phase after reperfusion originates
      from infiltrating macrophages possibly in anticipation of the migration and
      adhesion of additional macrophages into the affected testis.

PMID- 16891796
TI  - Diabetes mellitus after resection of hepatocellular carcinoma with hypoglycemia
      in a dog.
AB  - A 10-year-old male beagle was referred to us with seizure related to hypoglycemia
      and a large intraabdominal mass. Based on various types of imaging and a
      laparoscopic biopsy, the intraabdominal mass was diagnosed as a hepatocellular
      carcinoma (HCC) of the quadrate lobe. The hypoglycemia was suspected to be
      associated with the HCC. After lobectomy of the quadrate lobe was performed,
      blood glucose levels continued to increase to higher than normal values and sugar
      was detected in the urine. The dog was diagnosed as diabetes mellitus (DM) and
      was treated with insulin for over two years after the surgery.

PMID- 16891797
TI  - Relationship between trace elements status in mane hair and atrial fibrillation
      in horse.
AB  - To investigate the relationships between trace elements concentrations in hair
      and atrial fibrillation (AF) in horses, concentrations of nineteen trace elements
      were detected in hair using the particle induced X-ray emission (PIXE) method.
      The horses were assigned to either control (n=22, no abnormalities) or AF groups
      (n=5) based on electrocardiograph findings. The mean concentrations of Ca and Zn
      in the hair of the AF group were significantly higher than those in the control
      group. The Zn/Cu ratio of the hair in the AF group (29.8 +/- 5.5) was
      significantly higher than that in the control group (23.4 +/- 2.2, P<0.05). The
      results of the present study suggest that there is a relationship between
      elevated concentrations of Ca and Zn in hair and AF.

PMID- 16891798
TI  - Clinical features of polyarteritis nodosa in Korea.
AB  - Polyarteritis nodosa (PAN) is a systemic vasculitis characterized by multi-organ
      involvement with protean manifestations. We evaluated the clinical features of
      PAN in Korea. Twenty-seven patients were diagnosed as PAN at Seoul National
      University Hospital between January 1990 and July 2003. The male-to-female ratio
      was 1.7:1 and mean age at onset (+/-SD) was 47.4+/-20 yr. Their presenting
      features at diagnosis were similar to those reported previously, i.e., myalgia,
      muscle weakness or leg tenderness (70%), fever (52%), weight loss >4 kg (44%),
      skin rash (44%), peripheral edema (33%), abdominal pain (33%), and
      arthralgia/arthritis (30%). However, the prevalence of testicular pain or
      tenderness was higher (24%) than reported previously and only three (11.5%) had
      HBsAg positivity without liver enzyme elevation. Nine patients (33%) had a five
      factor score (FFS) of 2. Fourteen patients (52%) responded to treatment, 2
      patients relapsed and 4 died within 1 yr of diagnosis. During a median follow-up
      of 55.5 months, three of the four PAN-related deaths had an initial FFS of 2. The
      clinical features of PAN were not significantly different from those reported
      previously. However, testicular pain or tenderness was more frequent and patients
      with a high FFS tended to have a poorer prognosis.

PMID- 16891799
TI  - Association of TNFA promoter region haplotype in Behcet's Disease.
AB  - Although the etiology of Behcet's Disease (BD; MIM 109650) remains to be clearly
      elucidated, levels of tumor necrosis factor alpha (TNF-alpha) have been reported
      to be significantly elevated in BD patients, and TNF-alpha blockers have been
      demonstrated to exhibit some degree of therapeutic efficacy for a certain subset
      of BD sufferers. In this study, we have conducted an analysis of the TNFA
      haplotypes in the promoter response element that affect the binding affinity of
      specific transcription factors, in order to characterize their association with
      the clinical features of BD. Six polymorphisms in the promoter region of TNFA
      were genotyped in 254 BD patients and 344 control subjects, via the PCR-RFLP
      technique. TNFA -1031*C, -863*A and -308*G alleles were associated with an
      increased risk of BD (p=0.030, OR=1.4; p=0.008, OR=1.5; p=0.010, OR=1.8,
      respectively). The sole TNFA haplotype -1031C-863A-857C-376G-308G-238G, was
      associated with a 1.6 fold increase in the risk of BD, whereas the TNFA haplotype
      -1031T-863C-857C-376G-308A-238G was associated with a 0.6 decreased risk of BD.
      The TNFA -1031*C, -863*A, -857*C and -308*G alleles were significantly associated
      with BD. The findings of this study, collectively, indicate that TNFA haplotypes
      in the promoter response elements may exert significant influence on
      susceptibility to BD.

PMID- 16891800
TI  - Atypical pathogens as etiologic agents in hospitalized patients with community
      acquired pneumonia in Korea: a prospective multi-center study.
AB  - Local epidemiologic data on the etiologies of patients hospitalized with
      community-acquired pneumonia (CAP) is needed to develop guidelines for clinical
      practice. This study was conducted prospectively to determine the proportion of
      atypical bacterial pathogens in adults patients hospitalized with CAP in Korea
      between October 2001 and December 2002. Microbiological diagnosis was determined
      by serology for antibodies to Mycoplasma pneumoniae, Chlamydia pneumoniae, and
      Legionella pneumophila. Nucleic acid of M. pneumoniae and C. pneumoniae in
      respiratory samples and Legionella antigen in urine samples were detected. The
      study population consisted of 126 patients (71 males, 55 females), averaging 54.6
      yr (SD+/-17.8), whose paired sera were available. An etiologic diagnosis for
      atypical pathogens was made in 18 patients (14.3%): C. pneumoniae 9 (7.1%), M.
      pneumoniae 8 (6.3%), and L. pneumophila 3 patients (2.4%). Streptococcus
      preumoniae and other typical pathogens were isolated from 36 patients (28.6%). Of
      126 patients, 16 (12.7%) were admitted to intensive care unit and atypical
      pathogens were identified in 5 patients (31.3%). Initial clinical features of
      patients with pneumonia due to atypical, typical or undetermined pathogens were
      indistinguishable. We conclude that atypical pathogens should be seriously
      considered in hospitalized patients with CAP, when initiating empiric treatment
      in Korea.

PMID- 16891802
TI  - Epidemiology of hemorrhagic fever with renal syndrome in endemic area of the
      Republic of Korea, 1995-1998.
AB  - We conducted an epidemiologic study to understand temporal and spatial patterns
      of hemorrhagic fever with renal syndrome (HFRS) in the Republic of Korea (ROK).
      We estimated the incidence among civilians in endemic areas through the active
      surveillance system during the major epidemic periods, from September to
      December, between 1996 and 1998. We also estimated the prevalence among Korean
      military personnel from 1995 to 1998. In addition, we assessed seroprevalence,
      subclinical infection rate, and vaccination rates in both civilians and military
      personnel. The incidence in civilians ranged from 2.1 to 6.6 per 100, 000 person
      months. The annual prevalence in the military personnel was 40-64 per 100, 000
      military populations, and remained generally constant throughout the study period
      with seasonal variation. This is the prospective epidemiologic data set on HFRS
      in the ROK since the inactivated Hantaan virus vaccine was licensed for use in
      the late 1990s. These results will be invaluable in establishing a national
      immunization program against HFRS.

PMID- 16891801
TI  - Serum vascular endothelial growth factor in pediatric patients with community
      acquired pneumonia and pleural effusion.
AB  - This study investigated the serum vascular endothelial growth factor (VEGF)
      levels in children with community-acquired pneumonia. Serum VEGF levels were
      measured in patients with pneumonia (n=29) and in control subjects (n=27) by a
      sandwich enzyme-linked immunosorbent assay. The pneumonia group was classified
      into bronchopneumonia with pleural effusion (n=1), bronchopneumonia without
      pleural effusion (n=15), lobar pneumonia with pleural effusion (n=4), and lobar
      pneumonia without pleural effusion (n=9) groups based on the findings of chest
      radiographs. We also measured serum IL-6 levels and the other acute inflammatory
      parameters. Serum levels of VEGF in children with pneumonia were significantly
      higher than those in control subjects (p<0.01). Children with lobar pneumonia
      with or without effusion showed significantly higher levels of serum VEGF than
      children with bronchopneumonia. For lobar pneumonia, children with pleural
      effusion showed higher levels of VEGF than those without pleural effusion.
      Children with a positive urinary S. pneumonia antigen test also showed higher
      levels of VEGF than those with a negative result. Serum IL-6 levels did not show
      significant differences between children with pneumonia and control subjects.
      Serum levels of VEGF showed a positive correlation with the erythrocyte
      sedimentation rate in the children with pneumonia. In conclusion, VEGF may be one
      of the key mediators that lead to lobar pneumonia and parapneumonic effusion.

PMID- 16891803
TI  - Metabolic syndrome is associated with delayed heart rate recovery after exercise.
AB  - Heart rate (HR) recovery after exercise is a function of vagal reactivation, and
      its impairment is a predictor of overall mortality and adverse cardiovascular
      events. While metabolic syndrome is associated with sympathetic overactivity,
      little is known about the relationship between metabolic syndrome and HR
      recovery. A symptom-limited exercise stress test in healthy subjects (n=1, 434)
      was used to evaluate HR recovery. Metabolic syndrome was defined according to the
      National Cholesterol Education Program's Adult Treatment Panel III (NCEP ATP-III)
      criteria. Seventeen percent of subjects had > or =3 criteria for metabolic
      syndrome. HR recovery was lower in men than women and in smokers than nonsmokers.
      The subject with metabolic syndrome (vs. without) showed lower HR recovery
      (10.3+/-11.6 vs. 13.6+/-9.7 per minute) and higher resting HR (64.3+/-10.3 vs.
      61.6+/-9.1 per minute). HR recovery correlated inversely to age (r=-0.25,
      p<0.0001), but not to resting HR or maximal oxygen uptake. Delayed HR recovery
      was associated with metabolic syndrome after an adjustment for age, sex, resting
      HR and smoking (p<0.01). Metabolic syn-drome is associated with impaired vagal
      reactivation. Adverse cardiovascular out-comes associated with metabolic syndrome
      may be mediated by the failure of vagal reactivation in addition to sympathetic
      overactivity.

PMID- 16891804
TI  - Granulocyte antibodies in Korean neonates with neutropenia.
AB  - Neonatal alloimmune neutropenia (NAN) is a disease that can cause severe and
      prolonged neutropenia in neonates. However, no report is available on the
      incidence of granulocyte antibody in neonates, the target antigen of this
      antibody, and the estimated incidence of NAN in Korea. Among a total of 856
      neonates admitted to a neonatal intensive care unit (NICU) over a five year
      period, a total of 105 neonates with neutropenia were enrolled in this study.
      Positive reactions were observed in the sera of six neonates (5.7%, 6/105) by
      mixed passive hemagglutination assay (MPHA). To confirm the presence of NAN, MPHA
      and granulocyte antigen typing (HNA-1a, -1b, -2a, -4a, and -5a) were performed on
      neonatal and maternal blood. To differentiate granulocyte antibody and HLA
      antibody, MPHA was also performed using HLA antibody adsorbed serum. We confirmed
      three cases (2.9%, 3/105) of NAN among neonates with neutropenia in which
      granulocyte antibody specificities (two anti-HNA-1b and one anti-HNA-1a) and
      fetomaternal granulocyte antigen mismatches were identified. In this study, the
      estimated incidence of NAN was 0.35% (3/856) among neonates admitted to NICUs in
      Korea.

PMID- 16891805
TI  - Primary systemic anaplastic large cell lymphoma in a single Korean institution:
      clinical characteristics and treatment outcome.
AB  - Despite advances in the characterization of anaplastic large cell lymphoma
      (ALCL), little data is available on Asian patients. We report here upon single
      Korean institution's experience regarding the clinical characteristics and
      outcomes of ALCL. We performed a retrospective study of 32 adults with ALCL. Most
      of the patients received anthracycline-based chemotherapy. Ann Arbor stage III
      IV, B symptoms, high-intermediate/ high International Prognostic Index (IPI), and
      extranodal disease at diagnosis were present in 56%, 44%, 41%, and 63%,
      respectively. Compared with Western studies, the male/female ratio (4.3) was
      markedly higher and skin (9%) and bone involvement (9%) were less frequent. The
      staining results for anaplastic lymphoma kinase were positive in 6 (33%) of 18
      cases available. The complete response (CR) rate was 62% (95% CI, 44-80%). With a
      median follow-up of 51.0 months, 5 yr overall survival was 40+/-11%. The 3 yr
      relapse-free survival for the 18 patients who achieved CR was 74+/-12%. Age,
      performance status, lactate dehydrogenase, extranodal disease sites number, and
      IPI were correlated with treatment response and survival. Our data suggest that
      Korean ALCL patients appear to have a higher male/female ratio, less frequent
      skin/bone involvement, and lower CR rate compared with those of Western studies.

PMID- 16891806
TI  - Comparison of serum beta 2-microglobulin and 24 hour urinary creatinine clearance
      as a prognostic factor in multiple myeloma.
AB  - A new staging system for multiple myeloma (MM) has utilized serum concentrations
      of beta2-microglobulin (Sbeta2M) and albumin as important prognostic factors for
      survival. Since Sbeta2M is an indicator of glomerular filtration rate, we
      compared the prognostic values of Sbeta2M and 24-hr urinary creatinine clearance
      (Ccr) in patients with MM. We retrospectively reviewed the records of 170 MM
      patients from January 1996 to November 2003 whose 24-hr urinary Ccr was available
      at the time of diagnosis. We found that pretreatment Sbeta2M was inversely
      related to Ccr (Spearman's correlation coefficient=-0.787). In univariate
      analysis, the hazard ratio (HR) of death was 1.043 (p<0.001) for Sbeta2M and
      0.985 (p<0.001) for Ccr. Multivariate analysis showed that Sbeta2M (HR 1.030,
      p=0.010) and Ccr (HR 0.993, p=0.059) were significant prognostic factors in
      patients' survival. In conclusion, 24-hr urinary Ccr may be utilized for staging
      of patients with MM.

PMID- 16891807
TI  - nm23-H1 protein expression and gene mutation in 150 patients with non-Hodgkin's
      lymphomas.
AB  - The metastasis-suppressing role of the nm23 gene in the metastatic spread of
      malignant tumor is still debated. We examined the nm23-H1 protein expression and
      gene mutation in non-Hodgkin's lymphomas to compare with the clinicopathologic
      parameters. The expression of nm23-H1 protein was immunohistochemically examined
      in 150 cases of non-Hodgkin's lymphomas; 85 diffuse large B cell lymphomas (DL
      BCL), 18 marginal zone B cell lymphomas (MZL), 3 mantle cell lymphomas, 25
      peripheral T cell lymphomas, not otherwise specified (TCLNOS), and 19 NK/T cell
      lymphomas (NK/T). Eighty-one cases (58 DLBCL, 6 MZL, 4 TCLNOS, and 13 NK/T) were
      studied for nm23-H1 gene mutation in exon 1 to 5. The high expression of nm23-H1
      protein was associated with the high IPI score (p=0.019) and the low survival
      rate of the patients (p=0.0039). The gene mutation of nm23-H1 was detected in
      10.3% of DLBCL and 30.7% of NK/T; but none in MZL and TCLNOS. The mutation was
      found in exon 1 in 5 cases, exon 2 in two cases, exon 4 in one case and both exon
      1 and 2 in two cases. Our results suggest that the expression of nm23-H1 protein
      can be used as a poor prognostic marker in non-Hodgkin's lymphomas, and the
      mutational change of gene may operate in the lymphomagenesis.

PMID- 16891809
TI  - Genetic alterations in primary gastric carcinomas correlated with
      clinicopathological variables by array comparative genomic hybridization.
AB  - Genetic alterations have been recognized as an important event in the
      carcinogenesis of gastric cancer (GC). We conducted high resolution bacterial
      artificial chromosome array-comparative genomic hybridization, to elucidate in
      more detail the genomic alterations, and to establish a pattern of DNA copy
      number changes with distinct clinical variables in GC. Our results showed some
      correlations between novel amplified or deleted regions and clinical status. Copy
      number gains were frequently detected at 1p, 5p, 7q, 8q, 11p, 16p, 20p and 20q,
      and losses at 1p, 2q, 4q, 5q, 7q, 9p, 14q, and 18q. Losses at 4q23, 9p23,
      14q31.1, or 18q21.1 as well as a gain at 20q12 were correlated with tumor-node
      metastasis tumor stage. Losses at 9p23 or 14q31.1 were associated with lymph node
      status. Metastasis was determined to be related to losses at 4q23 or 4q28.2, as
      well as losses at 4q15.2, 4q21.21, 4q 28.2, or 14q31.1, with differentiation. One
      of the notable aspects of this study was that the losses at 4q or 14q could be
      employed in the evaluation of the metastatic status of GC. Our results should
      provide a potential resource for the molecular cytogenetic events in GC, and
      should also provide clues in the hunt for genes associated with GC.

PMID- 16891808
TI  - Antigen-binding characteristics of circulating IgG autoantibodies to cytokeratin
      18 protein in patients with nonallergic asthma.
AB  - Cytokeratin 18 (CK18) protein was identified as an airway epithelial cell
      autoantigen associated with nonallergic asthma. Cleavage of CK18 protein by
      caspase-3 is a marker of early apoptosis in epithelial cells. It has been shown
      that the expression of active caspase-3 was increased in bronchial epithelial
      cells of asthmatic patients, when compared with healthy controls. To investigate
      the antigen-binding characteristics of IgG autoantibodies to CK18 protein in
      nonallergic asthma, the bindings of IgG autoantibodies to the fragments of CK18
      protein cleaved by caspase-3 were analyzed by Western blot using serum samples
      from three patients with nonallergic asthma. Recombinant human CK18 protein was
      treated by caspase-3 and cleaved into N-terminal fragment (1-397 amino acids) and
      C-terminal fragment (398-430 amino acids). The binding capacity of IgG
      autoantibodies to N-terminal fragment of CK18 was maintained in one patient and
      reduced in other two patients. IgG autoantibodies from all three patients did not
      bind to C-terminal fragment of CK 18. In conclusion, IgG autoantibodies to CK18
      protein from patients with nonallergic asthma seems to preferentially bind to the
      whole molecule of CK18 protein and their antigen-binding characteristics were
      heterogeneous among the patients with nonallergic asthma.

PMID- 16891810
TI  - Prognostic significance of infection acquisition sites in spontaneous bacterial
      peritonitis: nosocomial versus community acquired.
AB  - Spontaneous bacterial peritonitis (SBP) is an ascitic fluid infection as a
      complication of end stage liver disease. The outcome is related to the severity
      of hepatorenal function, gastrointestinal bleeding, and many others; however it
      is not well known whether the infection acquisition sites have an effect on the
      prognosis of SBP. In order to identify the prognostic significance of the
      acquisition sites, we studied 106 patients who were diagnosed as culture positive
      SBP between October 1998 and August 2003. Thirty-two episodes were nosocomial and
      74 were community acquired. Gram-negative bacilli such as Escherichia coli were
      dominant in both of the nosocomial and community-acquired SBPs. Despite
      significantly higher resistance to cefotaxime in nosocomial isolates compared to
      community-acquired isolates (77.8% vs. 13.6%, p=0.001), no difference was found
      regarding short or long term prognosis. Infection acquisition sites were not
      related to short or long term prognosis either. Shock, gastrointestinal bleeding
      and renal dysfunction were related to short term prognosis. Only Child-Pugh class
      C was identified as an independent prognostic factor of long-term survival.

PMID- 16891811
TI  - MET expression in sporadic renal cell carcinomas.
AB  - Although germline mutations of met proto-oncogene on human chromosome 7q31-34
      have been known as useful molecular markers of hereditary papillary renal cell
      carcinoma (RCC), the expression of MET, a product of met proto-oncogene, has not
      been fully studied in sporadic RCC, along with its clinical significance. We
      investigated the expression of MET by immunohistochemistry in 182 cases of renal
      neoplasm encompassing 145 RCC, 25 urothelial carcinomas of renal pelvis, and 12
      oncocytomas. MET was diffusely and strongly expressed in 90% of papillary RCC,
      all collecting duct carcinomas, and 92% of urothelial carcinomas of renal pelvis.
      On the contrary, clear cell RCC, chromophobe RCC, and oncocytomas were negative
      or focally positive for MET expression. In clear cell RCC, MET expression was
      positively correlated with high nuclear grade, presence of infiltrative growth,
      tumoral necrosis, papillary architecture, sarcomatoid component, tumoral
      involvement of the renal pelvis or ureter, involvement of the calyx, and
      lymphatic invasion. In conclusion, diffuse and strong expression of MET in
      papillary RCC and collecting duct carcinoma might be helpful in discriminating
      from the other subtypes of RCC with tubular or papillary growth. In case of MET
      expression observed in clear cell RCC, it might correlate with those
      clinicopathological parameters implying aggressive behavior.

PMID- 16891812
TI  - The clinical significance of serum and urinary neopterin levels in several renal
      diseases.
AB  - Neopterin is a pyrazino-pyrimidine compound, and is known to be a marker
      associated with cell-mediated immunity in various diseases. We hypothesized that
      the levels of serum and urine neopterin would be elevated in renal disease, and
      would correlate with certain clinical parameters. We evaluated serum and urinary
      neopterin levels in patients with several renal diseases, including nephrotic
      syndrome (NS, n=19), chronic renal failure (CRF, n=8), end stage renal disease
      (ESRD, n=64) and controls (n=22). Serum neopterin was elevated in patients with
      CRF and ESRD, as compared to controls. Urinary neopterin levels were also found
      to be elevated in patients with CRF and ESRD, as compared to controls. Serum
      neopterin levels showed significant positive correlation with age, serum BUN and
      creatinine levels, and inverse correlation with WBC, hemoglobin, hematocrit,
      serum albumin and total iron binding capacity. Urine neopterin levels exhibited
      positive correlation with age and serum creatinine levels, and inverse
      correlation with WBC, hemoglobin, hematocrit, BUN and serum albumin. In
      conclusion, increased serum and urinary neopterin levels were found in some
      patients with renal disease and were correlated with certain clinical parameters.

PMID- 16891813
TI  - Survival benefits of neoadjuvant chemotherapy followed by radical surgery versus
      radiotherapy in locally advanced chemoresistant cervical cancer.
AB  - The aim of this study was to analyze long-term survivals in patients with stage
      IB to IIA cervical cancer treated by neoadjuvant chemotherapy setting. Between
      February 1989 and January 1998, 94 women with previously untreated stage IB to
      IIA carcinoma of the uterine cervix who received cisplatin based neoadjuvant
      chemotherapy were enrolled in this study. All of patients with chemoresponse
      (complete response, n=15; partial response, n=47) and 16 patients with
      chemoresistance received radical surgery (RS group). The other 16 patients with
      chemoresistance received radiotherapy for definite treatment (RT group). In the
      RS group, the 10 yr survival estimation in patients with bulky tumors (diameter >
      or =4 cm, n=26) was similar to that with non-bulky tumors (83.3% vs. 89.3%,
      p=NS). In selected patients with chemoresistance, those treated by radiotherapy
      (n=16) showed significantly poorer survivals than those treated by radical
      surgery (n=16) (10 yr survival rates of RT (25%) vs. RS (76.4%), p=0.0111). Our
      results support that a possible therapeutic benefit of neoadjuvant chemotherapy
      plus radical surgery is only in patients with bulky stage IB to IIA cervical
      cancer. In cases of chemoresistance, radical surgery might be a better definite
      treatment option.

PMID- 16891814
TI  - Clinical experiences of fetal ovarian cyst: diagnosis and consequence.
AB  - Ovarian cysts are the most frequent, prenatally diagnosed intra-abdominal cysts.
      Fetal ovarian cyst often presents complication such as torsion and seems to be an
      indication for surgical intervention. In this study, we reviewed pre- and post
      natal medical records and ultrasonography of 17 fetuses that were diagnosed with
      ovarian cysts. In a total of 17 cases, postnatal surgery was performed in 7
      infants. Of these cases, four cases of ovarian cyst torsion were confirmed. In
      the remaining 10 fetuses, one case regressed completely during pregnancy, and the
      other nine cases including two complex cysts resolve spontaneously after birth.
      Postnatal symptomatic cysts or cysts with a diameter greater than 5 cm that do
      not regress or enlarge should be treated, but uncomplicated asymptomatic cysts
      less than 5 cm in diameter should only be observed and reassessed by serial
      ultrasonography. If they regress spontaneously, no surgical intervention is
      necessary independent of their sonographic findings.

PMID- 16891816
TI  - Relationship between metabolic syndrome and familial history of
      hypertension/stroke, diabetes, and cardiovascular disease.
AB  - This research analyzes the prevalence of metabolic syndrome (MS) in Korea and
      examines how the presence of a familial history of diseases related to MS, such
      as hypertension/stroke, cardiovascular disease, and diabetes, affect the
      development of MS in Koreans. The prevalence of MS and its components, as defined
      by the Nation-al Cholesterol Education Program Adult Treatment Panel guidelines,
      were evaluated in nationally representative samples of non-institutionalized
      civilian Koreans. This analysis is based on the 2001 Korea National Health and
      Nutrition Examination Survey, which used a stratified multistage probability
      sampling design. The final study included 5,742 adults who had completed the
      necessary health examinations and met the diagnosis of MS. The prevalence of MS
      was 25.5% in men and 28.7% in women. Odds ratio for MS among men with a familial
      history of hypertension/stroke was higher than that among men who did not have
      this history. The OR for MS among women with a familial history of
      hypertension/stroke or diabetes was higher than that among women who had no
      familial history of these diseases. These results show that familial history of
      hypertension/stroke and diabetes was significantly related to the presence of MS
      in both young men and women.

PMID- 16891815
TI  - Cutoff values of surrogate measures of insulin resistance for metabolic syndrome
      in Korean non-diabetic adults.
AB  - We investigated the cutoff values of surrogate of insulin resistance for
      diagnosing metabolic syndrome in Korean adults. The data from 976 non-diabetic
      individuals (484 men and 492 women) aged 30-79 yr were analyzed. We determined
      the odds ratios for the prevalence of metabolic syndrome according to the
      quartiles of fasting insulin, homeostasis model for insulin resistance (HOMA-IR),
      and quantitative insulin sensitivity check index (QUICKI) as independent
      variables, while adjusting for age, sex, and body mass index. The cutoff values
      of fasting insulin, HOMA-IR, and QUICKI were estimated by the areas under the
      receiver-operating characteristic (ROC) curves. The cutoff points for defining
      insulin resistance are a fasting insulin level of 12.94 microU/mL, HOMA-IR=3.04
      as the 75th percentile value, and QUICKI=0.32 as the 25th percentile value.
      Compared with the lowest quartile, the adjusted odds ratios for the prevalence of
      metabolic syndrome in the highest quartiles of fasting insulin, HOMA-IR, and
      QUICKI were 1.95 (1.26-3.01), 2.27 (1.45-3.56), and 2.27 (1.45-3.56),
      respectively. The respective cutoff values for fasting serum insulin, HOMA-IR,
      and QUIC-KI by ROC analysis were 10.57 microU/mL (sensitivity 58.5%, specificity
      66.8%), 2.34 (sensitivity 62.8%, specificity 65.7%), and 0.33 (sensitivity 61.2%,
      specificity 66.8%). Fasting insulin, HOMA-IR, and QUICKI can be used as surrogate
      measures of insulin resistance in Korean non-diabetic adults.

PMID- 16891817
TI  - Clinical and radiological manifestations of osteogenesis imperfecta type V.
AB  - We reviewed clinical manifestation of 12 patients from three Korean families.
      They showed mild to moderate bone fragility, and suggested an autosomal dominant
      inheritance pattern. Significant intrafamilial phenotype variability was obvious.
      Clinical, radiological, and histopathologic characteristics that distinguished
      this subtype from others include ossification of interosseous membrane of the
      forearm with radial head dislocation, hyperplastic callus formation, no evidence
      of type I collagenopathy and an abnormal histopathologic pattern. Severity of the
      interosseous membrane ossification was correlated with increasing age (p<0.01)
      and the radial head dislocation was thought to be a developmental problem rather
      than a congenital problem. Four children who had bisphosphonate treatment showed
      improved bone mineral density, radiological changes, and biochemical responses.
      Osteogenesis imperfecta type V was a distinctive subtype of osteogenesis
      imperfecta, which caused mild to moderate disability clinically.

PMID- 16891818
TI  - Primary osteosarcoma in patients older than 40 years of age.
AB  - Among the 665 patients who registered at our hospital, we reviewed 39 cases of
      high grade primary osteosarcoma in patients who were older than 40 yr of age. The
      aim of this study was to determine if a primary osteosarcoma in older patients
      has different clinical features, and a poorer prognosis than in younger patients.
      Two evaluations were performed. In the first, an attempt was made to determine
      the possible prognostic factors such as gender, location, size, alkaline
      phosphatase, radiological findings, chemotherapy intensity, chemotherapy-induced
      tumor necrosis, and surgical margin. The second evaluation involved assessment of
      whether there were any significant clinical differences between older patients
      and adolescents. According to the results, a primary osteosarcoma in older
      patients did not reveal any significant prognostic variables. A primary
      osteosarcoma in older patients showed a poorer prognosis due to relatively
      unusual locations, common abnormal radiological findings, and a poor response to
      chemotherapy. Therefore, careful attention should be paid to making an accurate
      diagnosis and new strategies for more effective treatment, including
      chemotherapy, must to be developed in order to achieve long term survival in
      older patients with osteosarcoma.

PMID- 16891819
TI  - Endoscopic dacryocystorhinostomy: creation of a large marsupialized lacrimal sac.
AB  - This retrospective study describes and evaluates the effectiveness of a modified
      technique of conventional endoscopic dacryocystorhinostomy (DCR) that minimizes
      the obstruction of a neo-ostium by creating an enlarged marsupialized lacrimal
      sac using mucosal flaps. Forty-two patients who had undergone 46 endoscopic DCR
      at a tertiary medical center, from 2002 to 2004, for correction of lacrimal
      system obstruction were investigated. The surgical technique involves elevation
      of a nasal mucosal flap, full sac exposure using a power drill, and shaping of
      the mucosal flap to cover denuded bone and juxtapose exposed sac mucosa.
      Postoperative symptoms and endoscopic findings of the neo-ostium were evaluated.
      Mean duration of follow-up was 5.9 months. An eighty-three percent primary
      success rate was observed, without any serious complications. Obstruction of the
      neo-ostium with granulation tissue was observed in eight cases, among which six
      underwent revision with success in all cases. Overall, 44 (96%) of 46 cases
      experienced surgical successes. Endoscopic DCR, a procedure in which a large
      marsupialized lacrimal sac is created from mucosal flaps, yields a very
      satisfactory success rate with straightforward and highly successful revision
      available for those in whom the primary procedure yields a substandard result.

PMID- 16891820
TI  - Clinical and genetic analysis of Korean patients with Miyoshi myopathy:
      identification of three novel mutations in the DYSF gene.
AB  - Miyoshi myopathy (MM) is an autosomal recessive distal muscular dystrophy caused
      by mutations in the dysferlin gene (DYSF) on chromosome 2p13. Although MM
      patients and their mutations in the DYSF gene have been found from all over the
      world, there is only one report of genetically confirmed case of MM in Korea.
      Recently, we encountered three unrelated Korean patients with MM and two of them
      have previously been considered as having a type of inflammatory myopathy. The
      clinical and laboratory evaluation showed typical features of muscle involvement
      in MM in all patients but one patient initially had moderate proximal muscle
      involvement and another showed incomplete quadriparesis with rapid progression.
      Direct sequencing analysis of the DYSF gene revealed that each patient had
      compound heterozygous mutations (Gln832X and Trp992Arg, Gln832X and Trp999Cys,
      and Lys1103X and Ile1401HisfsX8, respectively) among which three were novel.
      Although MM has been thought to be quite rare in Korea, it should be considered
      in a differential diagnosis of patients exhibiting distal myopathy.

PMID- 16891821
TI  - Vigabatrin and visual field defects in pediatric epilepsy patients.
AB  - We studied the prevalence, type and severity of vigabatrin (VGB)-attributed
      visual field defects (VFDs), and used these data to assess the associated risk
      factors in pediatric patients. Medical records were retrospectively reviewed for
      67 pediatric patients who received VGB alone or in combination with other
      antiepileptic drugs, and who had undergone visual field examinations using a
      Humphrey visual field analyzer. Of the 67 patients, 15 had VGB-attributed VFDs:
      13 had nasal arcuate type, 1 had nasal and temporal constricted type and 1 had
      nasal constricted type. In terms of severity, 7 patients had Grade I VGB
      attributed VFDs, 5 had Grade II, 2 had Grade III, and 1 had Grade IV. Although
      there were no significant differences between the VFD and non-VFD groups with
      regards to all tested parameters, there were no cases of VGB-attributed VFDs in
      patients with total treatment durations <2 yr and cumulative doses <10 g/kg. In
      conclusion, the prevalence of VGB-attributed VFDs in VGB-treated pediatric
      epilepsy patients was 22%. The high frequency of VGB-attributed VFDs indicates
      that physicians should inform all patients of this risk prior to VGB treatment
      and perform periodic visual field examinations.

PMID- 16891822
TI  - Upregulation of proinflammatory cytokines in the fetal brain of the Gaucher
      mouse.
AB  - Gaucher disease is caused by a deficiency of glucocerebrosidase. Patients with
      Gaucher disease are divided into three major phenotypes: chronic
      nonneuronopathic, acute neuronopathic, and chronic neuronopathic, based on
      symptoms of the nervous system, the severity of symptoms, and the age of disease
      onset. The characteristics of patients with acute neuronopathic- and chronic
      neuronopathic-type Gaucher disease include oculomotor abnormalities, bulbar
      signs, limb rigidity, seizures and occasional choreoathetoid movements, and
      neuronal loss. However, the mechanisms leading to the neurodegeneration of this
      disorder remain unknown. To investigate brain dysfunction in Gaucher disease, we
      studied the possible role of inflammation in neurodegeneration during development
      of Gaucher disease in a mouse model. Elevated levels of the proinflammatory
      cytokines, IL-1alpha, IL-1beta, IL-6, and TNF-alpha, were detected in the fetal
      brains of Gaucher mice. Moreover, the levels of secreted nitric oxide and
      reactive oxygen species in the brains of Gaucher mice were higher than in wild
      type mice. Thus, accumulated glucocerebroside or glucosylsphingosine, caused by
      glucocerebrosidase deficiency, may mediate brain inflammation in the Gaucher
      mouse via the elevation of proinflammatory cytokines, nitric oxide, and reactive
      oxygen species.

PMID- 16891823
TI  - Temozolomide chemotherapy in patients with recurrent malignant gliomas.
AB  - Numerous studies have demonstrated the clinical activity of temozolomide, a
      second-generation alkylating agent, against malignant brain tumors, however, its
      activity has not been reported in an Asian population. This study analyzed the
      efficacy and toxicity of temozolomide in 25 adult patients with recurrent or
      progressive malignant gliomas after surgery and standard radiation therapy with
      or without chemotherapy, enrolled in our institution since July 2000. Sixteen
      patients had glioblastoma multiforme (GBM), six with anaplastic astrocytoma, and
      three with anaplastic oligodendroglioma. Of the 25 patients, 3 (12%) achieved a
      complete response (CR), 8 (32%) achieved a partial response (PR), 6 (24%) had
      stable disease (SD), and 8 (32%) had progressive disease (PD). Two patients
      achieved a CR, 4 patients achieved a PR, 3 patients had SD and 7 patients had PD
      in GBM, and 1 patient achieved a CR, 4 patients achieved a PR, 3 patients had SD,
      1 patient had PD in the non-GBM patients. Median progression free survival was 8
      weeks in GBM and 22 weeks in the non-GBM patients. The median overall survival of
      each group was 17 weeks and 28 weeks. Temozolomide demonstrated moderate activity
      in recurrent and progressive malignant gliomas without serious toxicity.

PMID- 16891824
TI  - Nonleukemic granulocytic sarcoma in the bile duct: a case report.
AB  - Granulocytic sarcoma (GS) is an extramedullary tumor composed of immature myeloid
      cells, typically occurring during the course of acute myelogenous leukemia. Non
      leukemic GS, that is, GS with no evidence of overt leukemia and no previous
      history of leukemia, is very rare, and even more unusual is nonleukemic GS of the
      bile duct. We report a case of nonleukemic GS of the bile duct. The patient was
      initially misdiagnosed as a bile duct carcinoma arising in the hilum of the liver
      (so-called Klatskin tumor), and received a right lobectomy of the liver.
      Histological examination of the tumor yielded the diagnosis of GS, and the bone
      marrow biopsy did not show any evidence of leukemia. Considering the risk of
      subsequent development of overt leukemia, the patient was treated with two cycles
      of combination chemotherapy as used in the cases of acute myelogenous leukemia.
      To date, he has remained free of disease 15 months after treatment.

PMID- 16891825
TI  - Giant fibrovascular polyp of the hypopharynx: surgical treatment with the
      biappoach.
AB  - Fibrovascular polyps of the esophagus and hypopharynx are benign tumors of the
      upper digestive tract. The majority of these polyps are located in the upper part
      of the esophagus but the hypopharyngeal fibrovascular polyps are only rarely
      seen. Most of them are surgically treated and this is usually done through a
      cervical incision, although some of them have been removed endoscopically. The
      authors report here on a case of a 63-yr-old-man with a giant fibrovascular polyp
      of the hypopharynx that extended into the stomach; this polyp was removed through
      simultaneous transcervical and transabdominal approaches because of the huge size
      of the polyp. The man presented with progressive dysphagia of 1 yr duration. The
      preoperative assessment revealed a giant polyp arising from the left arytenoid
      and extending into the stomach. The dimension of the polyp was about 26 x 10 x 4
      cm. The complete resection of the polyp with the simultaneous transcervical and
      transabdominal approaches was successful, and it was diagnosed as a fibrovascular
      polyp. The patient has been followed up without any recurrence for 6 month
      postoperatively.

PMID- 16891826
TI  - Peutz-Jeghers Syndrome with multiple genital tract tumors and breast cancer: a
      case report with a review of literatures.
AB  - We report here on the multiple genital tract neoplasms in a 41-yr-old Korean
      woman with Peutz-Jeghers Syndrome (PJS). The patient presented with lower
      abdominal pain. Her previous medical history was PJS and breast cancer. Pelvic
      ultrasound showed a multilocular cyst at the right adnexal region, diagnosed as
      bilateral ovarian mucinous borderline tumors. An ovarian sex cord tumor with
      annular tubules was incidentally diagnosed together with a minimal deviation
      adenocarcinoma of the uterine cervix and mucinous metaplasia of both the
      Fallopian tubal mucosa and the endometrium. Although the cases of multiple
      genital tract tumors with PJS has rarely been reported, the present case appears
      to be the first in Korea in which the PJS syndrome was complicated by multiple
      genital tract tumors and infiltrating carcinoma of the breast. The clinical
      significance of the multiple genital tract tumors and breast cancer associated
      with PJS is reviewed.

PMID- 16891827
TI  - Deflazacort for type-1 autoimmune hepatitis in a Korean girl.
AB  - Prednisone or prednisolone are the mainstay drug treatments for autoimmune
      hepatitis in children. However, long-term use of corticosteroid is associated
      with the risk of steroid-induced toxicities, and this situation requires newer
      immuno-suppressive agents for the treatment of autoimmune hepatitis, especially
      in growing children. An 11-yr-old Korean girl with type-1 autoimmune hepatitis
      discontinued prednisolone due to toxicities, i.e., hirsutism, buffalo hump, and
      skin striae, and remained clinical and biochemical remission under replacement of
      deflazacort and ursodeoxycholic acid combination therapy. A follow-up liver
      biopsy after 19 months of deflazacort and ursodeoxycholic acid treatment showed
      histologic remission.

PMID- 16891828
TI  - Myxedema ascites: case report and literature review.
AB  - Myxedema ascites caused by hypothyroidism is rare, so its diagnosis is often
      delayed and patients frequently receive unnecessary procedures such as liver
      biopsies and exploratory laparotomies. We report a 71-yr-old man with clinical
      ascites that was the first manifestation of hypothyroidism, and which resolved
      completely in response to thyroid hormone replacement therapy. To our knowledge,
      this is the first report of myxedema ascites in Korea. A review of the literature
      revealed 51 well-documented cases of myxedema ascites. Analyses of ascites from
      patients in this condition usually show high protein (>2.5 g/dL) and low white
      blood cell counts, with a high proportion of lymphocytes. A consistent feature is
      the good response to thyroid hormone replacement therapy, which has always led to
      resolution of the ascites. Myxedema ascites is thus rare but easy to treat; it
      should be borne in mind, especially if the ascites fluid has a high protein
      content.

PMID- 16891829
TI  - A case of hyperglycemic hyperosmolar state associated with Graves'
      hyperthyroidism: a case report.
AB  - Hyperglycemic hyperosmolar state (HHS) is an acute complication mostly occurring
      in elderly type 2 diabetes mellitus (DM). Thyrotoxicosis causes dramatic increase
      of glycogen degradation and/or gluconeogenesis and enhances breakdown of
      triglycerides. Thus, in general, it augments glucose intolerance in diabetic
      patients. A 23-yr-old female patient with Graves' disease and type 2 DM,
      complying with methimazole and insulin injection, had symptoms of nausea,
      polyuria and generalized weakness. Her serum glucose and osmolarity were 32.7
      mM/L, and 321 mosm/kg, respectively. Thyroid function tests revealed that she had
      more aggravated hyperthyroid status; 0.01 mU/L TSH and 2.78 pM/L free T3
      (reference range, 0.17-4.05, 0.31-0.62, respectively) than when she was
      discharged two weeks before (0.12 mU/L TSH and 1.41 pM/L free T3). Being
      diagnosed as HHS and refractory Graves' hyperthyroidism, she was treated
      successfully with intravenous fluids, insulin and high doses of methimazole (90
      mg daily). Here, we described the case of a woman with Graves' disease and type 2
      DM developing to HHS.

PMID- 16891830
TI  - Drug hypersensitivity to previously tolerated phenytoin by carbamazepine-induced
      DRESS syndrome.
AB  - Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome associated
      with anticonvulsant drugs is a rare but potentially life-threatening disease that
      occurs in response to arene oxide producing anticonvulsant such as phenytoin and
      carbamazepine. There have been many reports of cross reactivity among the
      anticonvulsants upon first exposure to the offending drugs. However, there has
      been few data describing the development of DRESS syndrome after switching
      medication from previously well-tolerated phenytoin to carbamazepine, and the
      induction of hypersensitivity to phenytoin by DRESS to carbamazepine. We
      experienced a case of a 40-yr-old man who had uncontrolled seizure that led to
      the change of medication from the long-term used phenytoin to carbamazepine. He
      developed DRESS syndrome after changing the drugs. We stopped carbamazepine and
      restored phenytoin for seizure control, but his clinical manifestations
      progressively worsened and he recovered only when both drugs were discontinued.
      Patch tests with several anticonvulsants showed positive reactions to both
      carbamazepine and phenytoin. Our case suggests that hypersensitivity to a
      previously tolerated anticonvulsant can be induced by DRESS to another
      anticonvulsant, and that the patch test may be a useful method for detecting
      cross-reactive drugs in anticonvulsant-associated DRESS syndrome.

PMID- 16891831
TI  - Recurrent juvenile nasopharyngeal angiofibroma treated with gamma knife surgery.
AB  - Radiosurgery has been rarely applied for juvenile nasopharyngeal angiofibroma
      (JNA) and cumulative reports are lacking. The authors report a case of successful
      treatment of recurred JNA with gamma knife surgery (GKS). A 48-yr-old man was
      presented with right visual acuity deterioration and brain magnetic resonance
      images (MRI) disclosed a 3 cm-sized intraorbital mass in the right orbit. He
      underwent a right fronto-temporal craniotomy and the mass was subtotally removed
      to preserve visual function. Histological diagnosis confirmed JNA in typical
      nature. However, the vision gradually worsened to fail four years after
      operation. MRI then showed regrowth of the tumor occupying most of the right
      orbit. GKS was done for the re-curred lesion. A dose of 17 Gy was delivered to
      the 50% isodose line of tumor mar-gin. During the following four-year follow-up
      period, the mass disappeared almost completely without any complications. Usually
      JNA can be exclusively diagnosed by radiological study alone. So this report of
      successful treatment of JNA with GKS may provide an important clue for the novel
      indication of GKS.

PMID- 16891832
TI  - Intradural disc herniation at L5-S1 mimicking an intradural extramedullary spinal
      tumor: a case report.
AB  - Intradural lumbar disc herniation is a rare pathological entity. The pathogenesis
      of intradural lumbar disc herniation is not known clearly. Intradural disc
      herniations usually occurred at the L4-L5 levels but have also been reported at
      other levels. However, intradural disc herniation at L5-S1 is quite rare. There
      are approximately nine reports in the English literature of intraradicular disc
      herniation at L5-S1. We described a 61-yr-old man with suspected intradural mass
      at the level of L5-S1 space. The patient presented with pain in the lower back
      and both lower legs for 4 months and a sudden exacerbation of the symptoms for 3
      days. Gadolinium-enhanced magnetic resonance imaging (MRI) demonstrated a large
      disc herniation at the L5-S1 level with an intradural component. L5 and S1
      laminectomy was performed, and dura was swollen and immobile. Subsequent durotomy
      was performed and an intradural disc fragment was removed. The patient had full
      recovery in 3 months. Intradural lumbar disc herniation must be considered in the
      differential diagnosis of mass lesions in the spinal canal. Contrast-enhanced MRI
      scans are useful to differentiate a herniated disc from a disc space infection or
      tumor.

PMID- 16891833
TI  - History of cochlear implants and auditory brainstem implants.
AB  - Cochlear implants have evolved during the past 30 years from the single-electrode
      device introduced by Dr. William House, to the multi-electrode devices with
      complex digital signal processing that are in use now. This paper describes the
      history of the development of cochlear implants and auditory brainstem implants
      (ABIs). The designs of modern cochlear and auditory brainstem implants are
      described, and the different strategies of signal processing that are in use in
      these devices are discussed. The primary purpose of cochlear implants was to
      provide sound awareness in deaf individuals. Modern cochlear implants provide
      much more, including good speech comprehension, and even allow conversing on the
      telephone. ABIs that stimulate the cochlear nucleus were originally used only in
      patients with neurofibromatosis type 2 who had lost hearing due to removal of
      bilateral vestibular schwannoma. In such patients, ABIs provided sound awareness
      and some discrimination of speech. Recently, similar degrees of speech
      discrimination as achieved with cochlear implants have been obtained when ABIs
      were used in patients who had lost function of their auditory nerve on both sides
      for other reasons such as trauma and atresia of the internal auditory meatus.

PMID- 16891834
TI  - Surgical aspects of cochlear implantation: mechanisms of insertional trauma.
AB  - The development of hybrid electroacoustic devices has made conservation of
      residual hearing an important goal in cochlear implant surgery. Our laboratory
      has recently conducted anatomical studies directed toward better understanding
      mechanisms underlying loss of residual hearing associated with electrode
      insertion. This paper provides an overview of observations based on
      microdissection, scanning electron microscopy and temporal bone histology
      relating to inner ear injury that may occur during implant surgery. Trauma to
      cochlear structures including lateral wall tissues, the basilar membrane, the
      osseous spiral lamina and the modiolus is considered in relation to the
      implications of specific types of injury for hearing preservation. These findings
      are relevant to the design of future implant devices and to various important
      issues regarding the surgical technique used for implantation, including the
      possible use of the round window as a portal of entry for electrode insertion.

PMID- 16891836
TI  - Factors influencing spoken language outcomes in children following early cochlear
      implantation.
AB  - Development of spoken language is an objective of virtually all English-based
      educational programs for children who are deaf or hard of hearing. The primary
      goal of pediatric cochlear implantation is to provide critical speech information
      to the child's auditory system and brain to maximize the chances of developing
      spoken language. Cochlear implants have the potential to accomplish for
      profoundly deaf children what the electronic hearing aid made possible for hard
      of hearing children more than 50 years ago. Though the cochlear implant does not
      allow for hearing of the same quality as that experienced by persons without a
      hearing loss, it nonetheless has revolutionized the experience of spoken language
      acquisition for deaf children. However, the variability in performance remains
      quite high, with limited explanation as to the reasons for good and poor
      outcomes. Evaluating the success of cochlear implantation requires careful
      consideration of intervening variables, the characteristics of which are changing
      with advances in technology and clinical practice. Improvement in speech coding
      strategies, implantation at younger ages and in children with greater preimplant
      residual hearing, and rehabilitation focused on speech and auditory skill
      development are leading to a larger proportion of children approaching spoken
      language levels of hearing age-mates.

PMID- 16891835
TI  - Histopathology of the inner ear relevant to cochlear implantation.
AB  - The most common forms of severe hearing loss and deafness are related to
      morphological changes in the cochlea. Many individuals with such forms of hearing
      disorders have received cochlear implants. It has been assumed that preservation
      of spiral ganglion cells is important for success of cochlear implants.
      Preservation of ganglion cells is negatively correlated with the duration of the
      hearing loss. It has, however, not been possible to reveal a relationship between
      the degree of survival of spiral ganglion cells and performance of cochlear
      implants. It is important to understand the histopathological changes that follow
      cochlear implantation. Insertion of cochlear implants may cause trauma to the
      basilar membrane, the spiral lamina, and the spiral ligament. Rupture of the
      basilar membrane may occur. Over time, new bone forms at the cochleostomy and
      along the implant track. Further investigation is necessary to evaluate the
      causes of variability of behavioral measures of performance.

PMID- 16891837
TI  - Central auditory development in children with cochlear implants: clinical
      implications.
AB  - A common finding in developmental neurobiology is that stimulation must be
      delivered to a sensory system within a narrow window of time (a sensitive period)
      during development in order for that sensory system to develop normally.
      Experiments with congenitally deaf children have allowed us to establish the
      existence and time limits of a sensitive period for the development of central
      auditory pathways in humans. Using the latency of cortical auditory evoked
      potentials (CAEPs) as a measure we have found that central auditory pathways are
      maximally plastic for a period of about 3.5 years. If the stimulation is
      delivered within that period CAEP latencies reach age-normal values within 3-6
      months after stimulation. However, if stimulation is withheld for more than 7
      years, CAEP latencies decrease significantly over a period of approximately 1
      month following the onset of stimulation. They then remain constant or change
      very slowly over months or years. The lack of development of the central auditory
      system in congenitally deaf children implanted after 7 years is correlated with
      relatively poor development of speech and language skills [Geers, this vol, pp 50
      65]. Animal models suggest that the primary auditory cortex may be functionally
      decoupled from higher order auditory cortex due to restricted development of
      inter- and intracortical connections in late-implanted children [Kral and
      Tillein, this vol, pp 89-108]. Another aspect of plasticity that works against
      late-implanted children is the reorganization of higher order cortex by other
      sensory modalities (e.g. vision). The hypothesis of decoupling of primary
      auditory cortex from higher order auditory cortex in children deprived of sound
      for a long time may explain the speech perception and oral language learning
      difficulties of children who receive an implant after the end of the sensitive
      period.

PMID- 16891838
TI  - Brain plasticity under cochlear implant stimulation.
AB  - The benefit of cochlear implantation crucially depends on the ability of the
      brain to learn to classify neural activity evoked by the cochlear implant. Brain
      plasticity is a complex property with massive developmental changes after birth.
      The present paper reviews the experimental work on auditory plasticity and
      focuses on the plasticity required for adaptation to cochlear implant
      stimulation. It reviews the data on developmental sensitive periods in auditory
      plasticity of hearing, hearing-impaired and deaf, cochlear-implanted, animals.
      Based on the analysis of the above findings in animals and comparable data from
      humans, a cochlear implantation within the first 2 years of age is recommended.

PMID- 16891839
TI  - Speech processing in vocoder-centric cochlear implants.
AB  - The principles of the most recent cochlear implant processors are similar to that
      of the channel vocoder, originally used for transmitting speech over telephone
      lines with much less bandwidth than that required for transmitting the
      unprocessed speech signal. An overview of the various vocoder-centric processing
      strategies proposed for cochlear implants since the late 1990s is provided
      including the strategies used in different commercially available implant
      processors. Special emphasis is placed on reviewing the strategies designed to
      enhance pitch information for potentially better music perception. The various
      noise suppression strategies proposed over the years based on multi-microphone
      and single-microphone inputs are also described.

PMID- 16891840
TI  - Auditory brainstem implants: surgical aspects.
AB  - Patients with neurofibromatosis type 2 often develop bilateral life-threatening
      vestibular schwannoma necessitating tumor removal, which results in deafness. We
      developed the auditory brainstem implant (ABI) in order to be able to
      electrically stimulate the cochlear nucleus complex in patients with bilateral
      cochlear nerve injury from bilateral schwannoma. After tumor removal, the
      electrode array of the ABI is inserted into the lateral recess of the fourth
      ventricle and placed over the surface of the ventral and dorsal cochlear nuclei.
      The ABI is designed to stimulate auditory neural structures within the cochlear
      nucleus in order to convey salient cues about the frequency, amplitude, and
      temporal characteristics of sounds. To date, more than 200 patients have received
      an ABI device at our institution. Recently, penetrating ABIs were introduced, and
      preliminary results of penetrating ABIs are discussed in this paper. The surgical
      anatomy of the nucleus and surgical placement of the ABI in patients with
      neurofibromatosis type 2 are described, and surgical considerations in this group
      of challenging patients are detailed.

PMID- 16891841
TI  - A guide to the positioning of brainstem implants using intraoperative electrical
      auditory brainstem responses.
AB  - The number of electrodes that elicit usable auditory sensations with an auditory
      brainstem implant varies significantly between subjects. For those with only very
      few, movement of the array by only a few millimetres could make a significant
      improvement to their outcome, but yet the point at which this is normally
      discovered is during activation, weeks after the surgery. The number of the
      electrodes that are able to stimulate the auditory system can be more reliably
      assured by the use of electrophysiologic guidance in the placement of the
      implanted electrode array. This chapter describes a procedure for the use of
      electrophysiology to aid placement in the operating room. The procedure involves
      stimulating the individual electrodes and recording electrical auditory brainstem
      responses (EABR) as an aid in positioning the electrode array. This procedure
      makes it possible to position the majority of electrodes over the surface of the
      cochlear nucleus thus minimising stimulation of other cranial nerves, which might
      result in undesirable side effects. Correctly positioned electrodes elicit an
      EABR response with between 1 and 4 peaks with average latencies approximately (in
      ms) 0.7 (0.4-0.9), 1.5 (1.2-1.9), 2.7 (2.1-3.4) and 3.7 (3.4-4.0). These waves
      likely correspond to waves III-VI of the traditional ABR (and wave II if an
      excitable stump of the auditory nerve is present). No further peaks within a 10
      ms window should be seen nor should activation of other cranial nerves occur. The
      response to stimulation of bipolar combinations of electrodes covering lateral,
      medial and distal positions provide information about the insertion depth. In
      individuals with a large lateral recess, measuring other combinations may assist
      in sideways and rotational orientation of the electrode array.

PMID- 16891842
TI  - Auditory outcomes in tumor vs. nontumor patients fitted with auditory brainstem
      implants.
AB  - Auditory brainstem implants (ABIs) are currently indicated for patients older
      than 12 years with neurofibromatosis type 2 (NF2) who had bilateral schwannoma
      removed. Over the last 10 years, we have extended the indications for ABIs to
      nontumor children and adult patients with cochlear or cochlear nerve injuries or
      malfunctions who would not benefit from a cochlear implant. We have provided ABIs
      for patients with cochlear nerve aplasia and other injuries, and patients in whom
      any benefit was, or would be, severely compromised as in extensive cochlear
      ossification. In the present chapter we report our recent findings in adult ABI
      patients and compare the psychophysical and speech perception outcomes in tumor
      with those in nontumor patients. We demonstrate that the ABI can stimulate the
      central auditory system in a way that gives the ability of open set speech
      understanding, and can thus be indicated in nontumor adult patients who are not
      candidates for a cochlear implant. From April 1997 to January 2006, a total of 80
      patients, 62 adults and 18 children, were fitted with ABIs in the University of
      Verona ENT Department; age ranged from 14 months to 70 years. Twenty-six patients
      had NF2 with bilateral vestibular schwannoma removal, and 54 had nontumor
      diseases of the cochlear nerve or cochlea. The retrosigmoid approach was used in
      all patients. All patients had a functioning implantation, and no complications
      were observed during the operation, activation as well as long-term use of the
      ABI. All patients, except 1 (NF2), reported auditory sensations with activation
      of various numbers of electrodes (from 5 to 21). Different electrodes elicited
      different pitch sensations. At 1 year after implantations nontumor adults scored
      from 12 to 100% in open set speech perception tests (average 59%), and tumor
      (NF2) patients scored from 5 to 30% (average of 11%). The differences between
      these results are statistically significantly (p < 0.01). To investigate the
      cause of the differences in performance between tumor and nontumor ABI
      recipients, a series of psychophysical tests were done consecutively in 39 adult
      patients with implants (25 nontumor and 14 tumor patients) from May 1999 to April
      2004 and with a follow-up of at least 1 year. The outcome of this study shows
      that: (1) The ABIs allow most tumor and nontumor patients to experience improved
      communication as well as awareness of environmental sounds. (2) Nontumor patients
      had better hearing outcomes than tumor patients when the variation in the
      auditory benefit with the ABI in relation to the patient's underlying
      pathological conditions were taken into consideration. (3) A significant number
      of nontumor patients are able understand speech at a level comparable to that of
      the most successful cochlear implant users including conversational telephone
      use. (4) The ABI represents the tool for hearing rehabilitation in patients with
      profound hearing loss who cannot be fitted with cochlear implants.

PMID- 16891846
TI  - The unique features of hyperparathyroidism in developing countries and the
      problem of vitamin D deficiency.

PMID- 16891844
TI  - Physiological basis for cochlear and auditory brainstem implants.
AB  - Cochlear implants bypass functions of the cochlea that have been regarded to be
      fundamental for discrimination of the frequency (or spectrum). Frequency
      discrimination is essential for discrimination of sounds, including speech
      sounds, and the normal auditory system is assumed to make use of both (power)
      spectral and temporal information for frequency discrimination. Spectral
      information is represented by the place on the basilar membrane that generates
      the largest amplitude of vibration on the basilar membrane. Evidence has been
      presented that the temporal representation of frequency is more robust than the
      place representation and thus regarded more important for speech discrimination.
      The fact that some cochlear implants provide good speech discrimination using
      only information about the energy in a few spectral bands seems to contradict
      these studies. In that way, frequency discrimination may be similar to
      trichromatic color vision, which is based on the energy in only three different
      spectral bands of light, accomplished by different color-sensitive pigments in
      the cones of the retina. Cochlear nucleus implants (ABIs) also bypass the
      auditory nerve, which does not perform any processing. Therefore, it may be
      expected that ABIs are equally efficient as cochlear implants. However,
      experience from the use of ABIs in patients with bilateral vestibular schwannoma
      has not been encouraging, but recent studies of the use of ABIs in patients with
      other causes of injuries to the auditory nerve have shown similar speech
      discrimination as achieved with modern cochlear implants. Cochlear implants and
      ABIs are successful in providing speech discrimination because of redundancy in
      the processing in the ear, redundancy of the speech signal and because the
      auditory nervous system has a high degree of plasticity. Expression of neural
      plasticity makes the auditory nervous system adapt to the change in demands of
      processing of the information provided by cochlear implants.

PMID- 16891843
TI  - Basis of electrical stimulation of the cochlea and the cochlear nucleus.
AB  - Sensorineural hearing loss is the most common form of deafness in humans. In
      patients with a severe-profound sensorineural hearing loss therapeutic
      intervention can only be achieved by direct electrical stimulation of the
      auditory nerve via a cochlear implant, or - in cases where a cochlear implant is
      not a surgical option - neurons within the central auditory pathway via an
      auditory brainstem implant. This paper reviews the basis of electrical
      stimulation of these structures with an emphasis on pathophysiology and safety.

PMID- 16891847
TI  - A rare cause of hydronephrosis: invasive mole.

PMID- 16891848
TI  - Continuous subcutaneous insulin infusion in type 1 diabetic Saudi children: a
      comparison with multiple daily insulin injections.

PMID- 16891849
TI  - RE: a comparison of handsearching versus EMBASE searching of the Annals of Saudi
      Medicine to identify reports of randomized controlled trials.

PMID- 16891850
TI  - [Clinical pharmacology of nucleoside and nucleotide reverse transcriptase
      inhibitors].
AB  - Options for antiretroviral therapy in patients infected with HIV continue to
      expand as new drugs are integrated into treatment regimens. Nucleoside/nucleotide
      reverse transcriptase inhibitors (Nt/NRTIs) remain the backbone of highly active
      antiretroviral therapy (HAART). Although this is the oldest class of
      antiretrovirals, pharmacokinetic and pharmacodynamic properties have been less
      studied as compare to protease inhibotors (PIs) and non-nucleoside reverse
      transcriptase inhibitors (NNRTIs). The aim of this article is to review the
      current status of clinical pharmacology onf Nt/NRTIs, highlighting the issues
      with clinical interest. Therefore, implications of intracellular pharmacokinetics
      on dosing schedule, potential for drug-drug interaction and pharmacodynamics is
      discussed.

PMID- 16891851
TI  - Applications of LightCycler Staphylococcus M-GRADE assay to detect Staphylococcus
      aureus and coagulase-negative staphylococci in clinical blood samples and in
      blood culture bottles.
AB  - We evaluated the applicability of the LightCycler Staphylococcus M(GRADE0 assay
      on artificially infected blood samples from healthy donors and on clinical
      specimens of 31 hospitalized patients. The sensitivity and specificity of the
      assay for detecting Staphylococcus aureus was 100% in blood samples, and 100% in
      blood culture bottles, when data from the BACTEC 9120 blood culture system were
      taken as gold standard. The same specificity and sensitivity was found during the
      search for CoNS (Coagulase Negative Staphylococci) in blood culture bottles,
      whereas a 93.33% sensitivity and 100% specificity was observed for detecting CoNS
      directly in blood clinical specimens.

PMID- 16891852
TI  - [Bacterial meningitis in adults: a retrospective multicentric study in Tuscany
      (Italy)].
AB  - The Infectious Diseases Unit of Lucca Hospital conducted a multicentric
      retrospective study to evaluate the epidemiological and clinical features of
      adult patients affected by bacterial meningitis attending all the Infectious
      Diseases Units of Tuscany (Italy) from July 1999 to June 2004. A specific
      questionnaire was sent to all the units to collect information about each case of
      bacterial meningitis occurring in patients older than sixteen. Patients with
      meningitis by Mycobacterium tuberculosis were excluded from the analysis. Nine
      out of 12 Infectious Diseases Units of Tuscany took part in the study and 197
      cases were identified. Most cases of meningitis occurred during 2002 with a
      slight reduction in cases in subsequent years. Streptococcus pneumoniae and
      Neisseria meningitidis were the most frequently isolated pathogens with an
      increase in diagnosis from 1999 to 2004; in 23.8% of patients no pathogens were
      isolated, with a reduction in meningitis from unknown aetiology from 1999 to
      2004. Most patients were treated with a combination of two antibiotics, and
      corticosteroid drugs were added to the therapy; in the group of patients treated
      with corticosteroid drugs invalidating complications occurred in 23% of cases and
      5% of patients died. In all, 27 out of 197 subjects (13.7%) developed
      invalidating complications and 20 out of 197 patients (10.2%) died.

PMID- 16891853
TI  - [Epidemiologic surveillance of multi-drug resistant Pseudomonas aeruginosa in
      Mantova Hospital (Italy)].
AB  - For the period 2002-2005 we verified and compared the data of the prevalence and
      resistance of Pseudomonas aeruginosa (PA) isolated in Mantova Hospital (Italy)
      with the data from the international database. From the first six-month period of
      2004 a significant increase was found (9% vs 28.8%) in the prevalence of multi
      drug resistant PA (MDR-PA). The principal wards involved were the Intensive Care
      Unit and the Department of Respiratory Diseases. A significant increase in
      resistance rates was observed for all antimicrobials tested, in particular for
      aztreonam, ceftazidime, ciprofloxacin, gentamycin and imipenem. The lowest dual
      resistance rates were observed between amikacina with piperacillin/tazobactam,
      while the highest were for those that included ciprofloxacin and beta-lactams
      (aztreonam, cefepime). In this study we confirm the importance of continuous
      surveillance of laboratory data and tightening local control measures for
      nosocomial infections in order to prevent the spread and selection of MDR-PA.

PMID- 16891854
TI  - [Enterobiasis during 2002-2003 in Perugia province: beyond diagnostics].
AB  - Between 2002 and 2003 we examined cellophane tapes of 119 children, both
      symptomatic and apparently asymptomatic. Eggs of Enterobius vermicularis were
      observed in 13.4% of children. This helminth is the most frequent in Italy, but
      it is as yet unrecognized, probably due to parasitological laboratories not being
      consulted, resulting in incomplete epidemiological data. We recall the biological
      aspects of this nematode and suggest the need for sound diagnosis to ensure
      proper surveillance of this exclusively human infection.

PMID- 16891856
TI  - [Syphilis in sixteenth-century in Bologna. Health care and social assistance
      (part two)].
AB  - Syphilis arrived in Bologna in the summer of 1495, after Fornovo's battle on the
      Taro where Charles VIII's army, following the invasion of Naples, fought against
      the anti-French league who faced up to the invaders as they withdrew. It was the
      battle-weary Bolognesi, prisoners, deserters and probably some prostitutes
      following the French and mercenary army who introduced the infection into the
      city. At the beginning of the syphilis epidemic, the disease was very aggressive
      with particularly visible symptoms and many resulting deaths. Subsequently,
      contemporaries mention an abatement of this aggressivity in time spans that
      varied, but in no cases exceeded 60 years. In 1507 Bologna lost its political
      autonomy, becoming dependent on Rome. This was symptomatic of the upheavals
      throughout Italy in the sixteenth century. In this situation of economic and
      institutional crisis the Bolognesi were able to react with decision to the
      epidemic, re-converting the municipal hospital dedicated to S. Maria dei Guarini
      during the sixteenth century. This hospital, specializing in treating syphilis,
      was called "Ospedale di San Giobbe". It was closed in 1798, after the entry of
      the French army into Bologna. In 1560 the Bolognesi, realising that the most
      important causes of the spread of syphilis were social degradation, prostitution
      and poverty, founded another institution for the poor and for the prevention of
      prostitution. This institution was developed by the Opera dei Mendicanti and
      provided hospitality during the 1590 famine, in a city of 55,000 inhabitants, for
      as many as 1400 poor and sick. We also present the cure (guaiac and mercury) that
      they used at the time against syphilis. In such a difficult historical period
      beset with political and economic problems, the Bolognesi established two
      important institutions and showed that social solidarity is a value for the whole
      population.

PMID- 16891857
TI  - The case for case reports: avoiding statistical seduction.
AB  - The management of patients with cancer teaches us the worth of logical thought,
      the advantage of flexibility of thinking and the thrill of occasionally doubting
      the experts. Asking questions and learning from the answers teaches us how to
      think. On the other hand, searching for the single best treatment, when no single
      treatment works for all patients, leads to a sort of intellectual tyranny that
      has numerous names: the gold standard, the community standard, best practice, and
      evidence-based medicine (EBM), with the implication that to take an alternative
      management route is substandard and unethical.

PMID- 16891855
TI  - Nosocomial spondylodiskitis with epidural abscess and CSF fistula cured with
      quinupristin/dalfopristin and linezolid.
AB  - Nosocomial infections after spinal surgery are relatively uncommon but
      potentially serious. The goal of diagnostic evaluation is to determine the extent
      of infection and identify the microorganism involved. Neuroimaging provides
      accurate information on correct topography, localization and propagation of the
      infection. Microbiological data are able to give aetiological causes. In this
      patient with severe, chronic polymicrobial spine infection with epidural abscess
      and CSF fistula due to multidrug-resistant organisms, the cure was achieved with
      long-term antimicrobial specific therapy with quinupristin-dalfopristin (50 days)
      and linezolid (100 days) with mild side effects. This positive result was due to
      combined medical and surgical treatment.

PMID- 16891858
TI  - Impact of TNF-alpha and IL-6 levels on development of cachexia in newly diagnosed
      NSCLC patients.
AB  - OBJECTIVES: We investigated the role of cytokines tumor necrosis factor-alpha
      (TNF-alpha) and interleukin-6 (IL-6) in cachexia development in newly diagnosed
      nonsmall cell lung cancer (NSCLC) patients. METHODS: : We evaluated 44 (M/F:41/3)
      NSCLC patients and 12 (M/F:10/2) age matched healthy smokers. NSCLC cases with a
      weight loss of > or =10% consisted the cachectic group (n:23, M/F:21/2) and the
      ones with <10% weight loss consisted the noncachectic group (n:21, M/F:19/2).
      RESULTS: Body mass index (BMI) of cachectics was significantly lower than that of
      noncachectics (21.0 +/- 2.9 versus 24.5 +/- 3.6, P = 0.02) and controls (21.0 +/-
      2.9 versus 25.5 +/- 2.6, P = 0.01). Serum TNF-alpha level did not differ between
      cachectic and noncachectics (37.3 +/- 39.1 and 51.6 +/- 84.2 pg/mL,
      respectively). However, it was significantly higher in NSCLC patients compared
      with controls (44.1 +/- 64.3 and 15.1 +/- 14.3 pg/mL, P = 0.03). Serum IL-6 level
      was not different between 3 groups (6.4 +/- 4.1, 8.9 +/- 16.3, and 4.1 +/- 3.5
      pg/mL, respectively) but it correlated significantly with TNF-alpha (r = 0.4, P =
      0.006) and BMI (r = -0.3, P = 0.03). Erythrocyte sedimentation rate (ESR)
      correlated significantly with TNF-alpha (r = 0.4, P = 0.003) and BMI (r = -0.3, P
      = 0.03). Among 44 cases, survival of 12 and 17 patients was recorded in
      cachectics and noncachectics, with no statistical difference (12.2 +/- 3.7 and
      11.2 +/- 1.0 months, respectively). CONCLUSIONS: TNF-alpha and IL-6 levels did
      not differ significantly between cachectics and noncachectics. However,
      significant correlations between IL-6, BMI, and TNF-alpha suggested that these
      cytokines acted as cofactors in weight loss. Survival was neither influenced by
      BMI, nor the cytokine levels in the present study. The significant correlation of
      ESR with TNF-alpha suggested that ESR could provide valuable clue for
      considerable weight loss in the follow-up of NSCLC patients.

PMID- 16891859
TI  - Systemic treatment of malignant thymoma: a decade experience at a single
      institution.
AB  - OBJECTIVES: Thymic malignancies are rare tumors on the superior anterior
      mediastinum. Treatment of advanced stages includes chemotherapy. The objective of
      this analysis was to review the treatment of this disease in the past decade.
      METHODS: This is a retrospective analysis of the results obtained in a total of
      29 patients with advanced malignant thymomas who underwent systemic chemotherapy
      in the past 10 years at our institution. Sixteen received neoadjuvant
      chemotherapy in the attempt to shrink the tumor and then perform a radical
      operation. The others received chemotherapy as palliation. Platinum based
      chemotherapy was mainly used. RESULTS: The response rate to first-line
      chemotherapy was 50% in the neoadjuvant setting and 31% in the advanced setting.
      A better survival was observed in patients who underwent chemotherapy as part of
      their combined modality treatment, in patients with thymomas, and in patients
      without visceral metastases. Some patients responded to targeted therapies at
      relapse. CONCLUSIONS: A better understanding of the biology of this rare tumor
      may allow in the future the development of better therapies for the more
      aggressive tumor types (WHO type C), which appear to be increasing in frequency.

PMID- 16891860
TI  - Gemcitabine, ifosfamide, and cisplatin combination (GIP) in treatment of patients
      with locally advanced or metastatic nonsmall cell lung cancer: results of a phase
      II study.
AB  - OBJECTIVES: We have carried out a phase II study to evaluate the efficacy and the
      toxicity associated with the combination of gemcitabine, ifosfamide, and
      cisplatin (GIP) in chemotherapy-naive patients with advanced nonsmall cell lung
      cancer (NSCLC). METHODS: Each cycle consisted of treatment with ifosfamide (3000
      mg/m2) and gemcitabine (1500 mg/m2) on day 1, followed by cisplatin (100 mg/m2)
      and gemcitabine (1500 mg/m2) on day 15. Each treatment cycle was repeated every
      28 days. A maximum of 6 cycles were administered. RESULTS: Sixty NSCLC patients
      (23 stage III and 37 stage IV) were entered in this study. The median survival
      for all patients is 9 months (stage III: 12.3 months; stage IV: 7.5 months). The
      overall survival at 1 and 2 years is 38% and 17%, respectively (52% and 30% for
      stage III; 30% and 8% for stage IV). The median time to progression is 6.3 months
      (stage III: 8.8 months; stage IV: 3.6 months). Progression free survival at 1 and
      2 years for all patients is 22% and 8%. The response rate is 56% for patients
      with stage III disease and 27% for patients with stage IV disease. Among the
      grade 3/4 toxicities, hematological toxicity was the most frequent (59% of
      patients) followed by gastrointestinal toxicity (nausea/vomiting) in 21% of
      patients. CONCLUSION: The GIP combination yields an efficacy, in terms of
      response and survival, comparable to that reported with other triplet combination
      treatments for local advanced or metastatic NSCLC, with an acceptable toxicity
      profile.

PMID- 16891861
TI  - Peptide vaccination of patients with metastatic melanoma: improved clinical
      outcome in patients demonstrating effective immunization.
AB  - OBJECTIVES: Therapeutic peptide vaccines for melanoma continue to only
      demonstrate anecdotal success. We set out to evaluate the impact of low-dose GM
      CSF emulsified in Montanide ISA-51 on the immunogenicity of HLA-A2 restricted
      melanoma differentiation antigen peptide vaccines (MART-1, gp100 and tyrosinase)
      administered in separate subcutaneous injections. METHODS: We conducted a
      randomized phase II clinical trial of HLA-A2+ patients with metastatic melanoma
      that were immunized every 3 weeks with one of the following vaccine preparations:
      (A) peptides + Montanide ISA-51; (B) peptides + Montanide ISA-51 + GM-CSF (10
      microg); (C) peptides + Montanide ISA-51 + GM-CSF (50 microg). Immunization
      efficacy was determined by quantification of vaccine specific tetramer positive
      cytotoxic T cells in peripheral blood. Global assessment of immune competence was
      ascertained using DTH testing to common recall antigens as well as peripheral
      blood immunophenotyping. RESULTS: Twenty-five eligible patients were equally
      distributed across all 3 treatment groups. Only 9 patients demonstrated evidence
      of immunization. Most commonly, immune response was achieved to the gp100
      peptide. The addition of low-dose GM-CSF did not impact immunization efficacy.
      DTH reactivity to Candida appeared predictive of successful immunization.
      Successful immunization with the peptide vaccines was associated with improved
      clinical outcomes. CONCLUSIONS: The addition of low dose GM-CSF to peptide
      vaccines did not enhance immunogenicity. Higher doses of GM-CSF may be needed to
      achieve this effect and this is a testable hypothesis. Likewise, better patient
      selection based on immunologic status (DTH reactivity) may be helpful to better
      understand the clinical impact of therapeutic cancer vaccines.

PMID- 16891862
TI  - Same day Pegfilgrastim and CHOP chemotherapy for non-Hodgkin lymphoma.
AB  - OBJECTIVES: To determine if "same day" Pegfilgrastim (Pf) with CHOP chemotherapy
      for non-Hodgkin lymphoma impacts on nadir white blood count (WBC) levels or on
      the nadir day. METHODS: Ten patients with non-Hodgkin lymphoma treated with CHOP
      R; CHOP with liposomal Doxorubicin replacing H; or CVAD received 'same day' Pf in
      a minimum of one cycle of chemotherapy to a maximum of 6 cycles with 8 of 10
      patients receiving same day Pf for some but not all cycles allowing for
      comparison of nadir WBC levels within patients. RESULTS: A total of 43 cycles of
      chemotherapy were reviewed. Same day Pf was administered with 21 of 43 cycles in
      all 10 patients with 8 of 10 receiving 22 cycles without Pf as well. White blood
      count nadir level and nadir day were compared in 9 patients in whom same day Pf
      was or was not administered in selected cycles. One patient experienced febrile
      neutropenia in a single cycle. Median nadir count and nadir day for cycles
      delivered with same day Pf was 1500 cells/ml (range, 200-11,000) at 14 days
      (range, 7-14 days). Median nadir count and nadir day cycles not delivered with
      same day Pf was 1600 cells/m and day 14 (range, 7-14), respectively. Four of 21
      cycles (19%) delivered with same day Pf were associated with grade 4 leukopenia
      compared with 2 of 23 cycles (9%) delivered without same day Pf. With regard to
      the total 10 patient population 4 patients had a grade 4 leukopenia experience
      with same day Pf and 2 patients had a grade 4 leukopenia experience without same
      day Pf. Grade 4 leukopenia had a median nadir day of 7. CONCLUSIONS: Same day Pf
      may accentuate neutropenia in some patients with non-Hodgkin lymphoma receiving
      standard CHOP or CHOP-R chemotherapy but expanded studies are necessary to
      establish this point definitively. The accentuated neutropenia may be related to
      the specific chemotherapy regimen or drug, eg, cyclophosphamate since same day Pf
      was safe with regimens in which a non alkylating agent (taxane, gemcitabine,
      navelbine, cisplatin) was used with a weekly chemotherapy dosing schema and did
      not generate accentuated neutropenia.

PMID- 16891863
TI  - Do MSI-L sporadic colorectal tumors develop through "mild mutator pathway"?
AB  - BACKGROUND: The mutator pathway implied in the development of colorectal cancer
      (CRC) is characterized by microsatellite instability (MSI). MSI tumors can be
      subdivided according to the level of instability: MSI-H (high), MSI-L (low) or
      stable MSS. MSI-H CRC displays a well described distinct phenotype, but the true
      biologic significance of MSI-L is still uncertain. The objective of this study
      was to further clarify if the MSI-L phenotype could reflect a distinct pathway of
      tumor development with a different clinical behavior. METHODS: We analyzed the
      clinicopathological and genetic variables of 156 patients with sporadic CRC in
      relation with the level of MSI of the tumors. RESULTS: We have found that MSI-L
      tumors are someway in the middle of MSI-H and MSS CRC, as they share some
      features with each of the other 2 subgroups: left side location, lower incidence
      of LOH at MSH2 as MSS and Dukes B (stage II TNM) like MSI-H. Moreover, MSI-L
      tumors show higher incidence of KRAS mutations. CONCLUSION: We believe that MSI-L
      tumors could be considered a distinct phenotype that develops through a "mild
      mutator pathway."

PMID- 16891864
TI  - Oxaliplatin in combination with 5-fluorouracil (5-FU) and leucovorin (LV) in
      patients with metastatic gastric cancer (MGC).
AB  - OBJECTIVE: Treatment options for advanced or metastatic gastric cancer (A/MGC)
      are limited and inclusion of novel substances is necessary. Few studies have
      confirmed the activity and tolerability of the combination of oxaliplatin (OXA)
      and 5-fluorouracil (5-FU) modulated with leucovorin (LV) administrated to
      patients with A/MGC. The goal of current study was to evaluate the efficacy and
      toxicity of Folfox-4 regimen in patients with A/MGC. PATIENTS AND METHODS: Fifty
      six patients were treated with Folfox-4 regimen. Treatment was continued until
      disease progression, unacceptable toxicity or until a patient chose to
      discontinue treatment. Responses to treatment and toxicity were recorded
      according to the WHO criteria and NCI toxicity criteria. RESULTS: All patients
      were assessable for toxicity and response. Patients (71.4% male, 28.6% female)
      had a median age of 65 years (range, 28-78). All patients had histologically
      confirmed metastatic (89.3%) or advanced (10.7%) gastric cancer. Response was
      evaluated every 6 weeks; 1 complete (1.8%) and 23 (41.1%) partial remission were
      observed (overall response rate 42.9%). Twenty patients (35.7%) showed stable
      disease and 12 (21.4%) had a progressive disease. Median overall survival, time
      to progression and follow up were 10 months, 6 months, and 11.5 months,
      respectively. WHO grade 3 or 4 hematologic toxicities included leucopenia,
      neutropenia, thrombocytopenia, and anemia. No patient experienced neutropenic
      fever. Other grade 3/4 toxicities included nausea, vomiting, diarrhea,
      stomatitis, and anorexia. Three patients (5.3%) experienced grade 3 peripheral
      neuropathy. No treatment-related deaths were recorded. CONCLUSIONS: Folfox-4
      regimen is active and well tolerated in patients with advanced/metastatic gastric
      cancer.

PMID- 16891865
TI  - Paclitaxel poliglumex (PPX-Xyotax) and concurrent radiation for esophageal and
      gastric cancer: a phase I study.
AB  - OBJECTIVES: To determine the maximal tolerated dose (MTD) and dose limiting
      toxicities of poly(l-glutamic acid)-paclitaxel (PPX) and concurrent radiation
      (PPX/RT) for patients with esophageal and gastric cancer. METHODS: Patients with
      esophageal or gastric cancer receiving chemoradiation for loco-regional,
      adjuvant, or palliative intent were eligible. The initial dose of PPX was 40
      mg/m2/wk, for 6 weeks with 50.4 Gy radiation. Dose levels were increased in
      increments of 10 mg/m2/wk of PPX. RESULTS: Twenty-one patients were enrolled over
      5 dose levels. Sixteen patients had esophageal cancer and 5 had gastric cancer.
      Twelve patients received PPX/RT as definitive loco-regional therapy, 4 patients
      had undergone resection and received adjuvant PPX/RT, and 5 patients had
      metastatic disease and received PPX/RT for palliation of dysphagia. Dose limiting
      toxicities of gastritis, esophagitis, neutropenia, and dehydration developed in 3
      of 4 patients treated at the 80 mg/m2 dose level. Four of 12 patients (33%) with
      loco-regional disease had a complete clinical response. CONCLUSIONS: The
      maximally tolerated dose of PPX with concurrent radiotherapy is 70 mg/m2/wk for
      patients with esophageal and gastric cancer.

PMID- 16891867
TI  - Estrogen receptors evolution in neoadjuvant aromatase inhibitor (AI) therapy for
      breast cancer in elderly women: stability of hormonal receptor expression during
      treatment.
AB  - In France, 20% of breast cancers occur in women over the age of 70 and 10% in
      women over the age of 80. As these women are not included in screening programs,
      breast cancer is often diagnosed later, at the stage of a large tumor. PURPOSE:
      To analyze clinical response, possibilities of conservative treatment and course
      of hormonal receptors in patients receiving neoadjuvant aromatase inhibitor (AI)
      therapy for at least 6 months. PATIENTS AND METHODS: There were 75 patients, with
      a mean age of 75 +/- 8 years (range, 58-91 years) received AI for 6 months after
      the diagnosis of invasive breast cancer with positive hormonal receptors.
      Clinical and radiologic tumor reduction, the number of conservative treatments
      and the course of estrogens receptor-labeled cells were determined for each
      patient. RESULTS: All but 1 of these patients obtained clinical reduction of
      their tumor. Of these, 86% patients received conservative treatment. In the
      majority of patients, estrogen receptor (ER) level did not vary between the
      initial assay and analysis of the operative specimen. DISCUSSION AND CONCLUSION:
      Aromatase inhibitors are effective as neoadjuvant therapy in ER positive elderly
      patients with large tumors, as is tamoxifen. Changes in hormone receptor
      expression during treatment do not predict clinical response. In our experience,
      neoadjuvant AI therapy should be administered for at least 6 months to optimize
      clinical response before deciding upon surgery. Discrepancy observed in the
      literature could be explained by the duration of the treatment.

PMID- 16891866
TI  - Paclitaxel and epirubicin followed by cyclophosphamide, methotrexate and 5
      fluorouracil for patients with stage IIIC breast cancer with ten or more involved
      axillary lymph nodes.
AB  - OBJECTIVE: The aim of this study was to evaluate the feasibility of a combination
      of epirubicin and paclitaxel followed by intravenous (iv) cyclophosphamide,
      methotrexate, and 5-fluorouracile (CMF) as adjuvant treatment of breast cancer
      patients with 10 or more metastatic axillary lymph nodes. METHODS: Forty-four
      patients entered this multicenter study and received 4 cycles of epirubicin (E
      120 mg/m2 day 1, q3 weeks) and paclitaxel (T 135 mg/m2 day 1, q3 weeks), followed
      by 4 cycles of iv CMF (days 1 and 8, q4 weeks). Patients with positive hormonal
      receptors received sequentially tamoxifen associated with LH-RH analogue if
      premenopausal. The endpoints were the evaluation of the feasibility of this
      schedule and disease free survival (DFS). RESULTS: Median age of patients was 55;
      median number of positive axillary nodes was 14 (range, 10-47). Hormonal receptor
      status was positive in 57% of patients. The combination of epirubicin and
      paclitaxel was well tolerated; NCI grade 3/4 events were: leucopenia in 27% of
      patients, neutropenic fever in 5 patients, anemia in 7%, thrombocytopenia in 7%,
      nausea in 18%, vomiting in 14%, and neurotoxicity in 4%. CMF regimen caused a few
      cases of grade 3/4 hematologic toxicity. No cardiac toxicity was recorded. With a
      median follow-up of 59 months, 18 (41%) patients relapsed. Sites of relapse were
      mainly bone, skin/soft tissues, liver, and lung. Median DFS was 78 months, with a
      5-year rate of 60%. CONCLUSIONS: The combination of paclitaxel at low dose and
      epirubicin followed by CMF is a feasible regimen, which seems to be effective in
      high-risk node positive breast cancer patients and requires further
      investigations.

PMID- 16891868
TI  - A phase II study of higher dose docetaxel in androgen-independent prostate
      cancer.
AB  - OBJECTIVES: To assess the efficacy and toxicity profile of single agent docetaxel
      at a higher dose than previously evaluated in patients with androgen-independent
      prostate cancer (AIPC). PATIENTS AND METHODS: Patients with metastatic and
      progressive AIPC were treated with docetaxel 100 mg/m on day 1 of a 3-week cycle.
      RESULTS: Twenty-five patients with overt and rapid symptomatic deterioration from
      AIPC were entered into this study. Nine men achieved a reduction in PSA of >50%
      and 4 >80% for an overall PSA response of 52% (95% confidence interval [CI], 31
      73%). Sixty percent of men experienced pain relief. Of 16 subjects with
      measurable disease, 25% achieved partial response (95% CI, 0-48 months), 44%
      stable disease, and 31% progressed. Median time to progression was 4.5 months
      (95% CI, 2.9-6.1 month) and median survival was 9.3 months (95% CI, 5.7-12.9
      months). Toxicity was significant and included grade 3 or greater neutropenia
      (76%), dehydration (16%), thrombosis (8%), confusion (4%), and death (4%).
      CONCLUSION: Docetaxel is an active agent against AIPC and should be used
      judiciously. The side effect profile of the 100 mg/m dose was significant and
      cannot be recommended for everyday clinical practice.

PMID- 16891869
TI  - Phase II evaluation of docetaxel plus exisulind in patients with androgen
      independent prostate carcinoma.
AB  - OBJECTIVES: In this phase II study, the combination of docetaxel and exisulind (a
      GMP phosphodiesterase inhibitor) was given to patients with metastatic androgen
      independent prostate cancer (AIPC) to establish efficacy, assess toxicity, and
      determine pharmacokinetics of docetaxel administered alone and in combination
      with exisulind. METHODS: Fourteen patients with metastatic AIPC were registered
      to receive weekly docetaxel for 4 weeks, followed by 2 weeks of rest; repeated up
      to a maximum of 6 cycles. Exisulind 250 mg was given orally twice a day starting
      on day 8 of the study and taken continuously. RESULTS: All patients were
      evaluable for toxicity, response and survival. Grade 3 reversible toxicities
      included: fatigue, nausea, diarrhea, abdominal pain, rash, syncope, pulmonary
      edema, deep vein thrombosis, congestive heart failure, and elevations in
      transaminases, requiring therapy delays and/or dose reductions, or removal from
      therapy. Only 3 out of 14 patients (21.4%) had a 50% decline in prostate specific
      antigen (PSA) level that lasted > or =4 weeks; 1 out of 14 patients (7%) had a
      lymph node response. Median survival was 17.28 months. Docetaxel pharmacokinetics
      for 11 patients demonstrated mean +/- SD clearance values that were similar
      during week 1 and week 3 when exisulind had been added. CONCLUSIONS: : Overall,
      our trial indicated that the toxicity profile and efficacy of this regimen is
      unlikely to be substantially better than single agent docetaxel.

PMID- 16891870
TI  - Phase I study of pegylated liposomal doxorubicin in combination with ifosfamide
      in pretreated ovarian cancer patients.
AB  - OBJECTIVES: To determine the dose limiting toxicity, the maximum tolerated dose
      and the recommended dose of pegylated liposomal doxorubicin (PLD) in association
      with a fixed dose of ifosfamide (IFO) to patients with recurrent, advanced
      ovarian cancer (AOC). METHODS: Patients with progressing platinum-sensitive or
      resistant disease were included in 5 dose levels consisting of PLD (25 mg/m2 to
      45 mg/m2, day 1) combined with a fixed IFO dose administered as a continuous
      infusion (1700 mg/m2/d, day 1 to 3) to define the MTD on the basis of acute
      toxicity during the first 2 cycles, then confirm the MTD, by the evaluation of
      delayed toxicity (hand-foot syndrome). RESULTS: Forty-eight patients were
      treated. The MTD was determined in the first 29 patients to be dose level V (45
      mg/m2), with 2 cases of febrile neutropenia. The recommended dose (level IV)
      combines 40 mg/m2 PLD on day 1 and 1700 mg/m2/d IFO day 1 to day 3. The principal
      toxicity was hematotoxicity (grade 3-4 neutropenia 61.8% of patients, grade 3/4
      thrombcytopenia 7.2%, and grade 3/4 anemia 21.8%). Nonhematological toxicity
      essentially consisted of grade 3/4 nausea and vomiting (14%). Nineteen additional
      patients were included in levels III (11 patients) and IV (8 patients), to
      evaluate late-onset toxicity. No hand-foot syndrome was observed in the 48
      treated patients, confirming the identification of dose level IV as recommended
      dose. CONCLUSION: This study regimen presents an acceptable tolerance. The
      preliminary assessment of efficacy merits confirmation in a phase II study.

PMID- 16891871
TI  - Confidence intervals and survival estimates: a systematic review of 3 oncology
      journals.
AB  - PURPOSE: Kaplan-Meier methods generate an estimate of survival when follow-up is
      less than complete. Confidence intervals (CI) provide a range of values that is
      likely to contain the true result. We hypothesized that reporting of CI around
      survival estimates is not uniform. METHODS: We searched all articles in randomly
      selected issues of Journal of Clinical Oncology (JCO), Cancer, and International
      Journal of Radiation Oncology Biology, and Physics (IJROBP) years 1999, 2001, and
      2004. Articles reporting overall or median survival were reviewed to determine if
      CI were reported in text or graphical form. Data regarding disease site,
      intervention, study size, and type of study were collected. RESULTS: A total of
      313 articles reported overall or median survival from 35 issues of the 3 journals
      (IJROBP 115, JCO 132, Cancer 66). CI were reported in 97/313 (31.0%) articles
      reviewed. CI reporting was more common in prospective clinical trials (38%) than
      retrospective reviews (25%), P = 0.018. If patients were treated with
      chemotherapy the article was more likely to report CI (no chemo 20% versus chemo
      40%; P = 0.001). CI reporting varied with journal (IJROBP 20%, Cancer 29%, JCO
      42%, P = 0.001). CI reporting increased according to year of publication (25% in
      1999, 27% in 2001, and 41% in 2004, P = 0.03). CONCLUSION: A majority of studies
      in major oncology journals do not report CI with survival estimates. The
      likelihood of reporting CI is associated with study type (prospective versus
      retrospective), use of chemotherapy, journal, and year of publication.

PMID- 16891872
TI  - Angiogenesis in colorectal cancer: prognostic and therapeutic implications.
AB  - Angiogenesis is important for tumor growth and metastasis. This account reviews
      the clinicopathological studies conducted in the field of angiogenesis in
      colorectal cancer, the methods of assessing vascular-related characteristics in
      tissue sections and provides a background for the usefulness of antiangiogenic
      policies along with chemotherapy and radiotherapy. Highly angiogenic colorectal
      tumors are associated with aggressive histopathological features and poor
      patients' survival. Similarly, factors stimulating angiogenesis, such as vascular
      endothelial growth factor (VEGF), thymidine phosphorylase (TP), and others, are
      commonly related to increased vascular density (VD) and, therefore, to an
      unfavorable clinical course. Anti-VEGF agents have improved prognosis in patients
      with metastatic colorectal cancer, when added to standard chemotherapy. It is
      expected that, in addition to adjuvant chemotherapy and radiotherapy, agents
      blocking the stimulatory effect of VEGF on endothelial cells would prove
      beneficial to the patient.

PMID- 16891873
TI  - Lipomatous hypertrophy of the interatrial septum evidenced on positron emission
      tomography in a patient with thyroid cancer.

PMID- 16891874
TI  - Surgery and postoperative radiotherapy for adenoid cystic carcinoma of the lung.

PMID- 16891875
TI  - Alveolar soft-part sarcoma: a cardiac metastasis as a rare site of relapse.

PMID- 16891876
TI  - Urethral stone formation after permanent radioactive seed implant for prostate
      cancer.

PMID- 16891878
TI  - Acute pancreatitis.
AB  - PURPOSE OF REVIEW: This review presents advances in our understanding of the
      pathobiologic responses of acute pancreatitis from studies using animal models of
      experimental pancreatitis as well as results of key clinical trials and
      observations. RECENT FINDINGS: The reports during the past year show significant
      advances in our understanding of the pathobiology of acute pancreatitis. In
      particular, there are findings presented that are relevant to our further
      understanding of pancreatic intracellular digestive enzyme activation; the
      pancreatic inflammatory response; and cell death responses such as necrosis as
      apoptosis. Other reports add to understanding of the control of microcirculatory
      disturbances in acute pancreatitis, and of the role of the pancreatic neural
      system in regulating the microcirculation as well as the pain associated with the
      disorder. Finally, there are clinical trials showing benefits of enteral feeding
      on outcome of acute pancreatitis as well as the finding that diclofenac prevents
      endoscopic retrograde cholangiopancreatography-induced pancreatitis. SUMMARY: Our
      understanding of the mechanistic processes that mediate the pathobiologic
      responses of pancreatitis is rapidly evolving. In addition, we now have initial
      evidence for potential treatment strategies for this disorder. Testing treatment
      strategies will lead to improved therapies and outcomes for patients with acute
      pancreatitis.

PMID- 16891879
TI  - Chronic pancreatitis.
AB  - PURPOSE OF REVIEW: As in our previous reviews, we endeavor to review important
      new observations in chronic pancreatitis made in the past year. Topics recently
      reviewed were truncated to accommodate a surge in publications on clinical
      aspects of chronic pancreatitis, which contained new observations or insights
      into new or old concepts. RECENT FINDINGS: Cystic fibrosis carriers have been
      found to be at increased risk of pancreatitis. Autoimmune pancreatitis may belong
      to a multiorgan immunoglobulin G4-related autoimmune disease, and the natural
      history of chronic pancreatitis differs among the etiologies. Diffusion-weighted
      magnetic resonance imaging improves upon previous methodologies for diagnosing
      reduced pancreatic exocrine secretion, and fecal elastase-1 has been found to be
      a poor test for diagnosing pancreatic malabsorption. Visceral hyperalgesia or
      heightened central pain perception may contribute to pain in chronic
      pancreatitis. Instruments are evolving to assess quality of life in chronic
      pancreatitis, and fibrolytic agents have been found to have therapeutic promise.
      SUMMARY: Researchers this past year have further characterized genetic, molecular
      and clinical aspects of chronic pancreatitis. Advancing the understanding of
      fibrogenesis, mechanisms of exocrine insufficiency, calcification, and pain and
      continuing development/modification of diagnostic tests should lead to improved
      prevention, detection and treatment of the condition. More accurate
      quantification of outcomes is critical for translating potential therapies from
      bench to bedside.

PMID- 16891880
TI  - Regulation of pancreatic acinar cell function.
AB  - PURPOSE OF REVIEW: Recent investigations into the regulation of pancreatic acinar
      cell function have led to a more detailed understanding of the mechanisms
      regulating digestive enzyme synthesis and secretion. This review identifies and
      puts into context those articles which further our understanding in this area.
      RECENT FINDINGS: The secretagogue receptors present on acinar cells, especially
      muscarinic and cholecystokinin, have been better identified and characterized.
      The complex control of intracellular Ca by intracellular messengers such as
      inositol trisphosphate, cellular ion pumps and membrane channels has become more
      clearly understood, including the identification of organelles sequestering
      intracellular Ca. In the area of Ca driven exocytosis, progress has been made in
      understanding the proteins present on the zymogen granules, especially Rabs and
      SNARE proteins, and the dynamic changes in actin filaments. Secretagogues have
      also been shown to enhance the translation of new protein by activation of the
      mammalian target of rapamycin pathway. Finally, considerable progress has been
      made in understanding the mechanisms regulating pancreatic growth in response to
      nutrients and following pancreatectomy or pancreatitis. SUMMARY: Understanding
      the mechanisms that regulate pancreatic acinar cell function is contributing to
      our knowledge of normal pancreatic function and alterations in diseases such as
      pancreatitis and pancreatic cancer.

PMID- 16891881
TI  - Key role of Kruppel-like factor proteins in pancreatic cancer and other
      gastrointestinal neoplasias.
AB  - PURPOSE OF REVIEW: To describe recent studies on Kruppel-like factor
      transcription factors and their relationship with gastrointestinal neoplasias, in
      particular pancreatic cancer. RECENT FINDINGS: Kruppel-like factor proteins are a
      subfamily of transcription factors characterized by the presence of a conserved
      DNA-binding domain comprising three Kruppel-like zinc fingers. Each distinct
      family member differs in its ability to regulate transcription, and, as a
      consequence, to influence cellular processes including cell growth and
      differentiation. Recently, a number of publications have provided evidence of the
      implication of Kruppel-like factor proteins in gastrointestinal carcinogenesis.
      SUMMARY: This article will focus on the results of studies in the field published
      in the last year.

PMID- 16891882
TI  - New advances in pancreatic imaging.
AB  - PURPOSE OF REVIEW: This review serves to highlight new technology and novel
      applications of existing techniques and their role in the management of
      pancreatic diseases, including acute and chronic pancreatitis, pancreatic cancer,
      and pancreatic cystic neoplasms. RECENT FINDINGS: Contrast-enhanced ultrasound
      has shown promise in evaluating the severity of acute pancreatitis, staging
      pancreatic cancer, and predicting malignancy in cystic neoplasms. Optical
      coherence tomography within the pancreatic duct appears to be able to
      differentiate malignant and normal pancreatic ducts. Spectroscopy may prove
      useful in differentiating focal chronic pancreatitis from malignancy.
      Multidetector-row computed tomography may provide more accurate information
      regarding cancer respectability and differentiation between ductal type of
      intraductal papillary mucinous tumors. SUMMARY: These new developments will help
      with the diagnosis and staging of pancreatic diseases.

PMID- 16891883
TI  - Pancreatic surgery.
AB  - PURPOSE OF REVIEW: To highlight publications in the past year in the field of
      pancreatic surgery. RECENT FINDINGS: Novel approaches to the neoadjuvant and
      adjuvant treatment of surgical candidates with pancreatic cancer have been
      reported. These new strategies may have significant impact on survival. Many
      studies detail the refinements of pancreatic surgery, including ways to diminish
      the complications of these procedures. Specific recommendations about less common
      pancreatic tumors including cystic tumors, endocrine tumors, and intraductal
      pancreatic mucinous neoplasms are included. Finally, the operative approaches to
      chronic pancreatitis have been studied and detailed. SUMMARY: The pancreas is a
      complex organ manifesting many different diseases - some fatal and others
      chronic. Increased interest in this organ from a growing list of experts has led
      to a better understanding of these diseases.

PMID- 16891884
TI  - Endoscopic management of esophageal malignancy: lessons learned from gastric
      cancer.

PMID- 16891885
TI  - Rectal carcinoids.
AB  - PURPOSE OF REVIEW: To provide an updated review of the diagnosis, management, and
      treatment of rectal carcinoid tumors, with special emphasis on minimally invasive
      surgical techniques to treat localized disease. RECENT FINDINGS: Carcinoids are
      morphologically and biologically heterogeneous neuroendocrine tumors that have
      malignant potential, and are most commonly found in the gastrointestinal tract.
      The incidence of all carcinoids appears to be increasing, which may reflect
      improved diagnostic modalities. The rectum is the third most common location for
      gastrointestinal carcinoids. Recent data have suggested that rectal carcinoids
      are over-represented in Black and Asian populations. The survival rate for
      patients with rectal carcinoids is superior to that of carcinoids found elsewhere
      in the gastrointestinal tract. Tumor size in rectal carcinoids is predictive of
      metastasis and can reliably guide management. Review of recent literature
      demonstrates good evidence that localized rectal carcinoids are amenable to local
      resection. SUMMARY: With widespread colorectal cancer screening, heightened
      awareness, and improved diagnostic modalities, the incidence of rectal carcinoids
      should continue to increase. There is evidence that convincingly demonstrates
      that patients with rectal carcinoids less than 2 cm in diameter, localized to the
      mucosa or submucosa, may be safely and effectively removed via minimally invasive
      resection.

PMID- 16891886
TI  - Endoscopic treatment of chronic radiation proctopathy.
AB  - PURPOSE OF REVIEW: Chronic radiation proctopathy is a complication of pelvic
      radiation therapy. The acute phase of radiation injury to the rectum occurs
      during or up to 3 months following radiation. Acute radiation injury can continue
      into a chronic phase or chronic radiation proctopathy may develop after a latent
      period of several months or years. Symptoms associated with the condition include
      diarrhea, rectal pain, bleeding, tenesmus, and stricture formation. Of the
      various symptoms, only bleeding from radiation-induced telangiectasias is
      amenable to endoscopic therapy. This paper summarizes the findings of experts in
      the field on endoscopic treatment of bleeding from chronic radiation proctopathy.
      RECENT FINDINGS: Medical management is generally ineffective in controlling
      bleeding from chronic radiation proctopathy. Surgical intervention has a high
      incidence of morbidity. Promising advances have been made in endoscopic therapy,
      including formalin, neodymium/yttrium aluminum garnet, argon and potassium
      titanyl phosphate laser treatments, as well as argon plasma coagulation. Argon
      plasma coagulation presents an effective, efficient, inexpensive and reasonably
      safe noncontact method for destruction of radiation telangiectasias. SUMMARY:
      Based on currently available data and trends, argon plasma coagulation is the
      favored treatment for bleeding from chronic radiation proctopathy.

PMID- 16891887
TI  - Endoscopic management of early gastric cancer.
AB  - PURPOSE OF REVIEW: Endoscopic mucosal resection for early gastric cancer is a
      widely accepted and practiced technique in countries such as Japan and China
      where the prevalence of gastric cancer is significantly higher than in the US.
      This review discusses standard endoscopic mucosal resection methods, as well as
      newly developed techniques. Data are reviewed in terms of complete resection
      rates and disease-free survival so as to allow endoscopists to determine which
      treatment options are best for their patients. RECENT FINDINGS: Within the past
      few years, new endoscopic mucosal resection and submucosal dissection techniques
      have been developed. These techniques may allow for the treatment of lesions that
      are not suitable for endoscopic treatment, especially in high-risk patients.
      SUMMARY: As gastroenterologists and surgeons in the West become more familiar and
      experienced with the techniques of endoscopic mucosal resection and submucosal
      dissection, patients will benefit from these minimally invasive therapeutic
      techniques. Although controlled studies are needed, in the future these methods
      may also be used to treat other early malignant conditions of the
      gastrointestinal tract.

PMID- 16891888
TI  - Endoscopic placement of enteral feeding catheters.
AB  - PURPOSE OF REVIEW: Critical to realizing increasing benefits of enteral nutrition
      are techniques for feeding tube placement. Feeding tubes can be placed by
      bedside, endoscopic, fluoroscopic, and surgical methods. This review encompasses
      noteworthy studies on endoscopic approaches to enteral feeding published from
      January 2005 to the present. RECENT FINDINGS: Studies involving placement of
      nasoenteric feeding tubes include description of new methods for endoscopic
      nasoenteric feeding tube placement using a push technique with a stiffened tube,
      a modification of the 'drag and pull' method using a distal suture tie, and
      placement using an ultrathin transnasal endoscopic technique compared with
      fluoroscopic placement. Recent studies involving percutaneous endoscopic
      gastrostomy tube placement have demonstrated equivalent outcomes of endoscopic
      and fluoroscopic approaches, description of unsedated placement using transnasal
      technique, and risk of percutaneous endoscopic gastrostomy site metastasis in
      head and neck cancer patients. Studies on percutaneous jejunal feeding tubes
      demonstrate: high complication rate and short functional duration of percutaneous
      endoscopic gastrojejunostomy and reported outcomes of direct percutaneous
      endoscopic jejunostomy placement. SUMMARY: Enteral nutrition access can be
      obtained by a variety of methods depending on local expertise and resources.
      Endoscopic approaches have equivalent or better outcomes than other methods;
      however, these methods may still have limitations and distinct complications.

PMID- 16891889
TI  - Endoscopic palliation of cholangiocarcinoma.
AB  - PURPOSE OF REVIEW: The current endoscopic palliative modalities for unresectable
      cholangiocarcinoma are reviewed, focusing on the emergent methods of endoscopic
      palliation. RECENT FINDINGS: Cholangiocarcinoma is a rare malignant tumor arising
      from biliary epithelium. Endoscopic retrograde cholangiopancreaticography can
      provide histological diagnosis through brush cytology of the bile duct, and newer
      cytologic techniques such as digital image analysis and fluorescent in-situ
      hybridization may improve the cytologic accuracy for diagnosing
      cholangiocarcinoma. Endoscopic ultrasonography can play an adjunctive role in the
      diagnosis and staging by facilitating tissue acquisition through fine needle
      aspiration of the tumor and surrounding lymph nodes. Most patients present with
      unresectable disease and features of biliary obstruction. This has led to an
      emphasis on the role of palliative care. Biliary stent placement is an effective
      method of palliating obstructive jaundice. Newer modalities such as photodynamic
      therapy, intraluminal brachytherapy, and high-intensity ultrasound therapy may
      result in improved survival and play a future role as an adjunctive therapy to
      surgical resection. SUMMARY: Several endoscopic palliative modalities have
      recently emerged. Among these, photodynamic therapy in addition to biliary stent
      placement appears to be a promising step towards the management of locally
      unresectable cholangiocarcinoma. Randomized, controlled trials are required,
      however, to further evaluate these therapies.

PMID- 16891890
TI  - Endoscopic resection of early gastric cancer: the Japanese perspective.
AB  - PURPOSE OF REVIEW: To examine recent advances in the techniques and technologies
      of endoscopic resection of early gastric cancer. RECENT FINDINGS: Endoscopic
      mucosal resection of early gastric cancer with no risk of lymph node metastasis
      has been a standard technique in Japan and is increasingly becoming accepted and
      regularly used in Western countries. Though this minimally invasive technique is
      a safe, convenient and efficacious method, it is insufficient for larger lesions.
      Difficulties in correctly assessing the depth of tumour invasion and increases in
      local recurrence by standard endoscopic mucosal resection have been reported in
      lesions larger than 15 mm. This is because such lesions are often resected
      piecemeal due to the technical limitation of standard endoscopic mucosal
      resection. New developments in endoscopic resection techniques to dissect the
      submucosa directly, called endoscopic submucosal dissection, allows resections of
      larger lesions en bloc. There are no limitations in resection size in endoscopic
      submucosal dissection, which is expected to replace surgery. This technique,
      however, still has higher complications rates than standard endoscopic mucosal
      resection and requires highly skilled endoscopists. SUMMARY: The techniques,
      indications, and pathological assessment methods of endoscopic resection of early
      gastric cancer are described so that proper treatment guidelines can be
      established and long-term outcome data can be assessed.

PMID- 16891891
TI  - Endoscopic therapy of benign pyloric stenosis and gastric outlet obstruction.
AB  - PURPOSE OF REVIEW: To examine the short and long-term success rates of balloon
      dilation of pyloric stenosis. RECENT FINDINGS: Several large studies have
      demonstrated high rates of success for the relief of symptoms from pyloric
      stenosis using through-the-scope balloons. These dilating balloons readily
      increase the diameter of the stenotic pylorus on average from 6 to 16 mm.
      Patients who require more than two dilations are at high risk of endoscopic
      failure and the need for surgical intervention. Rapid re-stenosis rates are
      observed in patients with malignant pyloric obstruction. Since many patients with
      benign pyloric stenosis have underlying ulcer disease, helicobacter infection is
      a relatively common finding. Eradication of this infection at the time of balloon
      dilation will ensure higher long-term success rates. SUMMARY: In summary, benign
      pyloric stenosis can be readily treated with endoscopic balloon dilation and
      should be the first-line therapy.

PMID- 16891892
TI  - Bibliography. Current world literature. Pancreas.

PMID- 16891894
TI  - Testing of high-volume sampler inlets for the sampling of atmospheric
      radionuclides.
AB  - Sampling of air for radioactive particles is one of the most important techniques
      used to determine the nuclear debris from a nuclear weapon test in the Earth's
      atmosphere or those particles vented from underground or underwater tests.
      Massive-flow air samplers are used to sample air for any indication of
      radionuclides that are a signature of nuclear tests. The International Monitoring
      System of the Comprehensive Nuclear Test Ban Treaty Organization includes
      seismic, hydroacoustic, infrasound, and gaseous xenon isotopes sampling
      technologies, in addition to radionuclide sampling, to monitor for any violation
      of the treaty. Lovelace Respiratory Research Institute has developed a large wind
      tunnel to test the outdoor radionuclide samplers for the International Monitoring
      System. The inlets for these samplers are tested for their collection
      efficiencies for different particle sizes at various wind speeds. This paper
      describes the results from the testing of two radionuclide sampling units used in
      the International Monitoring System. The possible areas of depositional wall
      losses are identified and the losses in these areas are determined. Sampling
      inlet type 1 was tested at 2.2 m s wind speed for 5, 10, and 20-microm
      aerodynamic diameter particles. The global collection efficiency was about 87.6%
      for 10-microm particles for sampling inlet type 1. Sampling inlet type 2 was
      tested for three wind speeds at 0.56, 2.2, and 6.6 m s for 5, 10, and 20-microm
      aerodynamic diameter particles in two different configurations (sampling head
      lowered and raised). The global collection efficiencies for these configurations
      for 10-microm particles at 2.2 m s wind speed were 77.4% and 82.5%, respectively.
      The sampling flow rate was 600 m h for both sampling inlets.

PMID- 16891895
TI  - National survey on the natural radioactivity and 222Rn exhalation rate of
      building materials in The Netherlands.
AB  - The present study reports on results of a nation-wide survey on the natural
      radioactivity concentrations and Rn exhalation rates of the prevailing building
      materials in the Netherlands. In total 100 samples were taken and analyzed for
      the activity concentrations of Ra, Ra, Th, and K and for their Rn exhalation
      rate. The sampled materials consisted of gypsum products, aerated concrete, sand
      lime and clay bricks, mortars and concrete, representing about 95% of the stony
      building materials used in the construction of Dutch homes. The laboratory
      analyses were performed according to two well-documented standard procedures, the
      interlaboratory reproducibility of which is found to be within 5% on average. The
      highest radionuclide concentrations were found in a porous inner wall brick to
      which fly ash was added. The second highest were clay bricks with average Ra and
      Ra levels around 40 Bq kg. Concrete and mortar show the highest exhalation rates
      with a fairly broad range of 1 to 13 microBq (kg s). Low natural radioactivity
      levels are associated with either natural gypsum (products) or gypsum from flue
      gas desulphurization units, and low exhalation rates with clay bricks. To
      evaluate the radiological impact the radioactivity concentrations in each sample
      were combined into a so-called dose factor, representing the absorbed dose rate
      in a room with a floor, walls and ceiling of 20 cm of the material in question.
      For that purpose, calculations with the computer codes MCNP, Marmer and
      MicroShield on the specific absorbed dose rates were incorporated in the paper.
      The results of these codes corresponded within 6% and average values were
      calculated at 0.90, 1.10, and 0.080 nGy h per Bq kg for the U series, the Th
      series, and K, respectively. Model calculations on the external dose rate, based
      on the incidence of the various building materials in 1,336 living rooms, are in
      accordance with measured data.

PMID- 16891896
TI  - Evaluation of mixing downstream of tees in duct systems with respect to single
      point representative air sampling.
AB  - Air duct systems in nuclear facilities must be monitored with continuous sampling
      in case of an accidental release of airborne radionuclides. The purpose of this
      work is to identify the air sampling locations where the velocity and contaminant
      concentrations fall below the 20% coefficient of variation required by the
      American National Standards Institute/Health Physics Society N13.1-1999.
      Experiments of velocity and tracer gas concentration were conducted on a generic
      "T" mixing system which included combinations of three sub ducts, one main duct,
      and air velocities from 0.5 to 2 m s (100 to 400 fpm). The experimental results
      suggest that turbulent mixing provides the accepted velocity coefficients of
      variation after 6 hydraulic diameters downstream of the T-junction. About 95% of
      the cases achieved coefficients of variation below 10% by 6 hydraulic diameters.
      However, above a velocity ratio (velocity in the sub duct/velocity in the main
      duct) of 2, velocity profiles were uniform in a shorter distance downstream of
      the T-junction as the velocity ratio went up. For the tracer gas concentration,
      the distance needed for the coefficients of variation to drop 20% decreased with
      increasing velocity ratio due to the sub duct airflow momentum. The results may
      apply to other duct systems with similar geometries and, ultimately, be a basis
      for selecting a proper sampling location under the requirements of single point
      representative sampling.

PMID- 16891897
TI  - Field comparison of commercially available short-term radon detectors.
AB  - We performed a comparison of commercially available short-term radon detectors in
      order to determine the accuracy and precision of the detectors under actual field
      conditions. We exposed fifteen radon detectors, under field conditions, from each
      of six companies to a reference radon concentration. Five of the six companies
      tested did not pass the U.S. Environmental Protection Agency's previously
      established accuracy guideline (all individual relative errors </= 25%) and four
      of the six companies failed the EPA's precision guideline [coefficient of
      variation </= 10% at 150 Bq m (4 pCi L)]. The findings suggest that the
      performances of commercially available radon detectors exposed under actual field
      conditions may not be as accurate or precise as those detectors available prior
      to the close of the EPA's National Radon Proficiency Program in 1998. It is
      unknown if this one-time "snap shot" represents the overall reliability of the
      accuracy and precision of commercially available radon detectors. Nonetheless,
      the findings suggest that additional double-blind testing of commercially
      available radon detectors under actual field conditions is warranted.

PMID- 16891898
TI  - The effects of dialysis on 131I kinetics and dosimetry in thyroid cancer patients
      -a pharmacokinetic model.
AB  - Currently, an accepted post-surgical treatment of patients with thyroid carcinoma
      is administration of an ablative dose of I. This treatment is well established
      based on extensive experience and modeling. However, for patients with renal
      disease, reduced iodine removal rates result in controversial thyroid doses and
      potentially excessive red bone marrow doses. There are differences of opinion
      regarding I dose recommendations ranging from a reduction in dose to an increase
      in dose compared with conventional amounts. Determination of suitable doses must
      take into account varying dialysis protocols and absorbed dose considerations to
      the thyroid and sensitive tissues such as red bone marrow. The specific aim of
      this study was to develop a simple yet comprehensive compartmental model for I
      kinetics in patients with thyroid carcinoma and end stage renal disease, which
      accounts for dialysis and provides absorbed dose estimates for the thyroid as
      well as the red bone marrow. STELLA, a compartmental modeling software program,
      was used to develop a kinetic model that includes the blood pool, thyroid,
      gastrointestinal tract, kidneys, bladder, and a conventional dialysis machine.
      Benchmarking was performed to demonstrate the validity of the model with data
      obtained from ICRP 30 and MIRD Dose Estimate Report No. 5. Iodine kinetics were
      simulated for normal patients, thyroid cancer patients, and patients with thyroid
      cancer and renal failure undergoing two standard types of dialysis, hemodialysis
      and continuous ambulatory peritoneal dialysis (CAPD). Results in this work show
      that thyroid doses to patients with thyroid cancer and renal failure on
      hemodialysis or CAPD are slightly higher than doses to patients with thyroid
      cancer and normal renal function. These results further indicate that red bone
      marrow doses to patients with thyroid cancer and renal failure on dialysis can be
      significantly higher than red bone marrow doses to patients with thyroid cancer
      and normal renal function, and thus these patients could benefit from a reduction
      in administered activity. Thyroid doses and red bone marrow doses to patients on
      standard hemodialysis depend on both dialysis frequency and the time interval
      between administration and first dialysis. The results in this study provide
      guidelines on how much activity a patient on dialysis should receive based on
      thyroid and red bone marrow absorbed dose (Gy MBq) considerations. This study
      should help to clarify some of the contradictory recommendations regarding I dose
      for thyroid carcinoma patients with renal failure.

PMID- 16891899
TI  - Significance of 14C and 228Ra in terms of the proposed Yucca Mountain high-level
      radioactive waste repository.
AB  - C and Ra are two of the radionuclides that have either been identified as being
      potentially significant in terms of releases from the proposed Yucca Mountain
      high-level radioactive waste repository, or are specifically cited for
      consideration and evaluation in the regulations promulgated by the U.S. Nuclear
      Regulatory Commission. The purpose of this study was to estimate the
      concentrations and associated doses for these two radionuclides, if released
      under conditions of a scenario assumed to apply to a repository containing some
      of the features of the one proposed at Yucca Mountain, NV, and to compare these
      estimates to the regulatory limits for that facility. For C, the postulated
      condition was that an annual fractional release of 10 of its total remaining
      inventory occurs beginning at 10,000 y after repository closure. For Ra, the same
      fractional release rate was assumed, but in this case it was presumed to occur
      when the Ra inventory was projected to reach a maximum at more than 10 y after
      repository closure. The estimated concentrations and doses were, in turn,
      compared to the concentration limit, specified in the Ground Water Protection
      Standards (GWPSs) in the case of Ra, or derived, in the case of C, on the basis
      of the regulatory dose rate limit. Due to the small inventory of C in the waste,
      and its short half-life relative to the performance period evaluated, its
      estimated concentration in the ground water would be slightly more than 4% of the
      derived GWPS. Due to the relatively small initial inventory of Th, the precursor
      of Ra, and the correspondingly small quantities of higher atomic number actinides
      that could, through decay, produce additional quantities of Th, its estimated
      concentration in the ground water would be less than 3% of the GWPS, leaving the
      remaining portion of the limit for potential contributions from Ra. At the same
      time, however, it must be recognized that, in this case, the regulations require
      that any contributions of naturally occurring Ra and Ra already present in the
      ground water must be included in the determination of compliance. If this is
      done, the total concentration of Ra, combined with the naturally occurring
      concentration of Ra, would be about 10.5% of the limit. In a similar manner, the
      committed doses due to the annual consumption of each of these two radionuclides
      in ground water and food, produced in the local biosphere, were evaluated in
      terms of the Individual Protection Standard (IPS). Based on these analyses, the
      estimated effective dose for C, using the coefficients in Federal Guidance Report
      (FGR) No. 13, was 4.15 muSv y, less than 3% of the IPS. For Ra, the comparable
      estimate at the time of maximum inventory, excluding in this case the
      contributions from naturally occurring Ra and Ra, was 7.39 muSv y, representing
      about 5% of the IPS. Based on the value assumed for the fractional release rate
      (10 y), it was concluded that neither C nor Ra will be significant in terms of
      either the applicable GWPS or the IPS. While it was recognized that, due to the
      time spans involved, these analyses were primarily an academic exercise, it is
      believed that the perspectives and accompanying insights are useful.

PMID- 16891901
TI  - Management of spent sealed radioactive sources in Turkey.
AB  - Spent radioactive sources (SRS) have been generated from industrial applications,
      research, and medicine in Turkey. In this study, management of SRS (Co, Cs) at
      Cekmece Waste Processing and Storage Facility (CWPSF) is described. Eleven Cs
      sources (total 851 GBq) and four Co sources (total 27.75 GBq) that had been used
      as levels and density gauges were conditioned. Reinforced metal drums (200 L in
      volume) and cement matrix were used for conditioning of these sources. In this
      way, greater confinement was achieved for long-term storage. Maximum dose rates
      at the surface of the conditioned waste package were determined. In addition to
      information about conditioning stages of the sources, various calculations that
      have been done for shielding are presented. Surface dose rates of the waste
      packages were 1.60 mSv h for Cs and 1.63 mSv h for Co. Measurements of the final
      waste packages were presented to fulfill the requirements (<2 mSv h) of
      transportation according to regulations for the safe transport of radioactive
      material.

PMID- 16891900
TI  - External doses to humans from 137Cs in soil.
AB  - Calculations of absorbed doses in organs of the human body and the total
      effective dose due to Cs in soil as a source of external exposure are presented
      in this work. Calculations were done using the MCNP-4B software package. The
      assumption was made that photons with an energy of 662 keV are emitted in a
      cylindrical volumetric source in soil up to the depth of 20 cm. Depth
      distributions of Cs at 19 locations around Kragujevac (a city in central Serbia)
      were measured by a HPGe detector. An ORNL phantom of an adult human standing on
      the soil above the center of a cylindrical radioactive source was used to
      calculate the conversion coefficients, i.e., absorbed doses in an organ per unit
      specific activity. The conversion coefficients in organs are given as a function
      of the source depth in soil. The largest absorbed dose was found in skin. The
      annual effective dose in humans was estimated from these calculations and the
      measured activity depth profile of Cs in soil. The average effective dose was
      found to be 3.17 microSv y. This value was rather small in comparison with other
      sources of natural ionizing radiation. One may conclude that Cs was a negligible
      source of external exposure in the area around the city.

PMID- 16891902
TI  - Cumulative dose assessment using thermoluminescence properties of porcelain
      isolators as evidence of a severe radiation accident in the Republic of Sakha
      (Yakutia), Russia, 1978.
AB  - The cumulated absorbed doses in four electric porcelain isolators collected at
      the site of the "Kraton-3" underground nuclear explosion in the Republic of Sakha
      (Yakutia), Russia, were evaluated using the thermoluminescence technique. The
      doses attributable to the accidental radioactive release from the explosion
      ranged from 1.2 to 10 Gy; the maximal value was detected for the isolator
      collected near the "Kraton-3" borehole. The measured thermoluminescence doses for
      two of the four samples analyzed are in reasonable agreement with the estimates
      of external gamma dose presented by earlier investigators of the site.

PMID- 16891907
TI  - Effect of clopidogrel on nitric oxide levels in an ischemia reperfusion model.
AB  - Ischemia and reperfusion injury is a pathologic process with serious
      consequences, arising due to interruption of arterial blood flow. Restored blood
      flow achieved after the ischemic period causes formation of oxygen radicals by
      activation of a variety of substances and systems. In this study, we investigated
      the effect of clopidogrel, an antithrombocyte agent, on tissue nitric oxide (NO)
      levels in an experimental ischemia reperfusion model. For this purpose, 6 hours
      of ischemia and 4 hours of subsequent reperfusion were applied to the right lower
      extremities of the subjects. Clopidogrel therapy was started in one of these
      groups 10 days before the process (study group). NO levels were measured in all
      groups in the muscle, lung, and liver tissues, and in plasma. Lung, plasma, and
      liver NO measurement values had statistically significant differences among the
      groups. There was no statistically significant difference in the measurements
      made on the muscle tissue. Clopidogrel, which has previously been reported to be
      suitable to be used as a preventive agent of ischemia reperfusion damage, has had
      a reducing effect on the NO levels in tissues in the ischemia reperfusion model
      created in our present study.

PMID- 16891908
TI  - Cocaine activates calcium/calmodulin kinase II and causes cardiomyocyte
      hypertrophy.
AB  - Cardiac hypertrophy occurs in as many as 47% of normotensive individuals who
      chronically use cocaine. We investigated the effects of cocaine, in
      concentrations commonly found in chronic cocaine users, on calcium/calmodulin
      kinase (CaMK), and whether cocaine can activate CaMK, increase cardiac myocyte
      protein expression, and cause cardiac hypertrophy in this manner. In series I to
      III, 0 (control) or cocaine in concentrations of 10 to 10 mol/L was added to
      cultured adult rat cardiac ventricular myocytes to determine by Western blots and
      by P incorporation the optimal treatment time and the optimal dose for CaMK
      activation. In series I, cocaine, 10 mol/L, increased myocyte CaMKII
      translocation from myocyte soluble to particulate fractions by > or =73 +/- 9% (P
      < 0.01) in comparison with controls but did not cause the translocation of CaMKI
      or CaMKIV. In series II and III, cocaine treatment of myocytes for 15 minutes
      increased maximal CaMKII activity by 86.5 +/- 13.3% (P < 0.001) and a cocaine
      dose of 5 x 10 mol/L increased CaMKII activity by 169.5 +/- 18.1% (P < 0.001). In
      series IV we measured by silver staining beta-myosin heavy chain protein (beta
      MHC) expression in myocytes before and after cocaine and also CaMK inhibition
      with KN-62 (1-[N,O-bis-(5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4
      phenylpiperazine). In these experiments, cocaine, 5x10 mol/L, increased myocyte
      protein concentration by 29.2 +/- 2.8%, and beta-MHC by 93.2 +/- 8.8% (P <
      0.001). In series V and VI, cocaine effects on calcium currents (ICa) and
      intracellular Ca ([Ca]i) were determined before and after CaMK inhibition with KN
      62 in rat myocytes. Cocaine, 10 mol/L, enhanced ICa peak amplitude in a voltage
      dependent manner (by 173.9 +/- 14.9% at -20 mV and by 38.4 +/- 6.9% at 0 mV P <
      0.01). Cocaine, 10 to 10 mol/L, in series VI promoted Ca transients from myocyte
      sarcoplasmic reticulum and increased [Ca]i to 607 +/- 141 x 10 mol/L (P < 0.05).
      KN-62 decreased cocaine-induced myocyte protein expression by 76.6%, and beta-MHC
      by 66.2% (P < 0.01) and significantly decreased cocaine-induced Ca transients and
      [Ca]i. We conclude that CaMKII activation is an important mechanism whereby
      cocaine can cause myocyte hypertrophy.

PMID- 16891909
TI  - Rho-kinase contributes to hypoxia/reoxygenation-induced cerebral endothelial
      dysfunction.
AB  - Hypoxia/reoxygenation (H/R) in vitro induced cerebral endothelial dysfunction is
      mediated by superoxide production. However, the intracellular pathways involved
      remain unclear. The present study was designed to investigate the involvement of
      Rho-kinase and its interaction with nitric oxide (NO) in cerebral endothelial
      dysfunction after H/R. Arterial diameter and intraluminal pressure were
      simultaneously measured in vitro on rat posterior cerebral arteries. Vascular NO
      production was determined by measuring stable NO metabolites nitrate/nitrite. H/R
      selectively inhibited cerebral vasodilation to the endothelium-dependent agonist
      acetylcholine (ACh, 0.01 to 10 micromol/L) and caused NO deficiency. H/R-impaired
      vasodilation to ACh was reversed by Y27632 (1 micromol/L), a specific inhibitor
      of Rho-kinase, but not by chelerythrine (1 micromol/L), a selective inhibitor of
      protein kinase C. Y27632 had no protective effect in the presence of N-nitro-L
      arginine methyl ester (L-NAME; 100 micromol/L), a specific endothelial NO
      synthase inhibitor. L-NAME (100 micromol/L) alone failed to modulate H/R-impaired
      vasodilation, so did L-arginine (3 mmol/L), a substrate for NO synthase. However,
      a stable NO donor diethylenetetra amine-NONOate (5 micromol/L) normalized H/R
      impaired dilation to ACh. In conclusion, H/R-induced endothelial dysfunction is
      associated with activation of Rho-kinase-dependent pathway and NO deficiency.
      Pretreatment with either Y27632 or the stable NO donor profoundly prevented H/R
      mediated cerebral endothelial dysfunction.

PMID- 16891910
TI  - Comparison of contractile responses in isolated mouse aorta and pulmonary artery:
      Influence of strain and sex.
AB  - Transgenic mice are often used to study the physiologic role of a known gene. The
      design of experiments with transgenic mice usually does not take into account
      strain and sex differences, at least in isolated vessels. Therefore, we have
      compared the contractile response of isolated aortae and isolated pulmonary
      arteries of male and female mice of different strains (CD1, BL6, and DBA).
      Contractile stimulation was achieved by depolarization due to KCl, alpha1
      adrenoceptor stimulation by phenylephrine and inhibition of protein phosphatase
      activity by cantharidin. In isolated aorta, strain-specific differences in
      contractility and sex-specific differences could be observed. The concentration
      of phenylephrine (PE) inducing half maximal contraction (EC50) was different
      between aortae from DBA male mice and the other strains tested. Phasic
      contractions of isolated aortic rings due to PE were seen in all mice except DBA
      male. In isolated pulmonary arteries, strain-specific differences and sex
      specific differences could be observed. The EC50-values of PE were not different
      between all groups. Phasic contractions due to PE were only seen in pulmonary
      arteries from CD1 male and BL6 female. In conclusion, strain- and sex-specific
      differences should be considered in selecting mice used for transgenesis or gene
      targeting experiments.

PMID- 16891911
TI  - Effects of Hct on L-NAME-induced potentiation of anaphylactic presinusoidal
      constriction in perfused rat livers.
AB  - Effects of hematocrit (Hct) on N-nitro-L-arginine methyl ester (L-NAME)-induced
      modulation of anaphylactic venoconstriction were determined in isolated perfused
      rat livers. The rats were sensitized with ovalbumin (1 mg), and the livers were
      excised 2 weeks later and perfused portally and recirculatingly under constant
      flow at Hct of 0%, 5%, 16%, and 22%. The hepatic sinusoidal pressure was
      estimated via the double occlusion pressure (Pdo), and the presinusoidal
      resistance (Rpre) and the postsinusoidal resistance (Rhv) were calculated. The
      antigen of ovalbumin 0.1 mg was injected into the reservoir at 10 minutes after
      pretreatment with L-NAME (100 microM) or D-NAME (100 microM). Perfusate
      viscosity, a determinant of vascular resistance and shear stress, was increased
      in parallel with Hct. In the D-NAME groups, antigen caused predominant
      presinusoidal constriction. The magnitude of venoconstriction was significantly
      smaller at Hct 0% than at Hct 5% to 22%, whereas no significant differences were
      found among Hct 5% to 22%. L-NAME potentiated the antigen-induced increase in
      Rpre, but not in Rpost at Hct 5% to 22% as compared with D-NAME. But the
      augmentative effects of L-NAME were similar in magnitude among Hct 5% to 22%.
      These findings suggest that hepatic anaphylaxis increases production of nitric
      oxide, which consequently attenuates anaphylactic presinusoidal constriction in
      rat livers, and that these effects are independent of perfusate Hct or viscosity
      in blood-perfused rat livers.

PMID- 16891912
TI  - Flavonoids from seabuckthorn protect endothelial cells (EA.hy926) from oxidized
      low-density lipoprotein induced injuries via regulation of LOX-1 and eNOS
      expression.
AB  - The present investigation was undertaken to determine the protective effects of
      flavonoids from seabuckthorn (FSBT), a traditional Chinese medicine, on
      endothelial cell line EA.hy926 injury induced by oxidized low-density lipoprotein
      (ox-LDL). Possible mechanisms were then explored. The effects of quercetin and
      isorhamnetin, 2 major components of FSBT, were examined as well. Indices such as
      cell viability, lactate dehydrogenase, nitric oxide (NO), superoxide dismutase,
      and superoxide were measured. Reverse transcription polymerase chain reaction,
      Western blot, and immunocytochemistry were employed to determine the endothelial
      constitutive NO synthase (eNOS) and lectinlike low-density lipoprotein receptor-1
      (LOX-1) expression. Cell viability decreased significantly after 24 hours
      treatment with ox-LDL, accompanied with apparent secretion disorders such as NO
      reduction and lactate dehydrogenase increase. FSBT pretreatment could remarkably
      prevent both cell death and secretion disorders in a concentration-dependent
      manner. Besides, it was observed that ox-LDL triggered superoxide production and
      suppressed the superoxide dismutase activity, both of which could be prevented by
      FSBT pretreatment. Moreover, ox-LDL inhibited eNOS expression and increased LOX-1
      expression, whereas FSBT pretreatment partly abolished these effects. Similar
      effects were obtained with quercetin and isorhamnetin, implying that they may
      contribute, at least in part, to the protective effects of FSBT. The data
      indicate that the protective effects of FSBT against ox-LDL induced endothelial
      cell injuries might derive from its antioxidant activity and its capability in
      modulating the expression of eNOS and LOX-1. And quercetin and isorhamnetin may
      contribute to these effects of FSBT.

PMID- 16891913
TI  - Ramipril treatment protects against nitrate-induced oxidative stress in eNOS-/-
      mice: An implication of the NADPH oxidase pathway.
AB  - The development of nitrate tolerance has been found to be associated with
      vascular production of superoxide anion (O2-*), generated mainly by the eNOS and
      NADPH oxidase pathways. The aim of our study was to investigate whether long-term
      angiotensin-converting enzyme inhibition by ramipril is able to protect against
      nitrate tolerance in the aortas of eNOS-deficient (eNOS-/-) mice and to assess
      the implication of the NADPH oxidase pathway. Therefore, 3 types of treatment
      were given to wild-type (WT) and eNOS-/- mice: group 1 received ramipril for 5
      weeks and a co-treatment with ramirpil plus nitroglycerine (NTG) during the last
      4 days, group 2 received only NTG, and group 3 served as control. Relaxations to
      NTG (0.1 nmol/L to 0.1 mmol/L) were determined on U44619, a thromboxane analogue,
      precontracted rings, and O2-* production were assessed on aorta homogenates with
      the lucigenin-enhanced chemiluminescence technique. Cyclic guanosine
      monophosphate and reverse-transcriptase-polymerase chain reaction analyses were
      performed on whole mouse aortas. In WT group 2, the concentration-effect curves
      to NTG were significantly shifted to the right: the pD2 was 6.16 +/- 0.17 (n = 6)
      vs 6.81 +/- 0.10 (n = 6) in WT group 3 (not exposed to NTG; P < 0.05) and O2-*
      production was enhanced from 100% +/- 11% (n = 9) to 191% +/- 21% (n = 6; P <
      0.01). In contrast, in WT group 1, the rightward shift was abolished: the pD2
      value was 6.73 +/- 0.13 (n = 6; NS vs group 3 WT) and O2-* production was 117% +/
      6% (n = 7; NS vs group 3 WT). In eNOS groups 1 and 3, similar data were
      observed: the pD2 values were 7.58 +/- 0.08 and 7.38 +/- 0.11 (NS) vs 6.89 +/-
      0.20 in eNOS group 2 (n = 6; P < 0.01). In the WT mice aortas, ramipril treatment
      significantly increased the cyclic guanosine monophosphate levels (reflecting
      nitric oxide availability), which returned to control values after in vivo co
      treatment with a bradykinin BK2 antagonist (Icatibant). In both strains,
      candesartan, an AT1 blocker, was also able to protect against the development of
      nitrate tolerance. Moreover, before NTG exposure, ramipril treatment decreased
      p22phox and gp91phox (essential NADPH oxidase subunits) mRNA expression in aortas
      from both mice strains. In conclusion, long-term ramipril treatment in mice
      protects against the development of nitrate tolerance by counteracting NTG
      induced increase in O2 production, which involves a direct interaction with the
      NADPH oxidase pathway and seems to be completely independent of the eNOS pathway.

PMID- 16891914
TI  - Linalyl acetate as a major ingredient of lavender essential oil relaxes the
      rabbit vascular smooth muscle through dephosphorylation of myosin light chain.
AB  - In a preliminary experiment, we found that lavender essential oil relaxes
      vascular smooth muscle. Thus, the present experiments were designed to
      investigate the relaxation mechanism of linalyl acetate as the major ingredient
      of lavender essential oil in rabbit carotid artery specimens. Linalyl acetate
      produced sustained and progressive relaxation during the contraction caused by
      phenylephrine. The relaxation effect of linalyl acetate at a concentration near
      the EC50 was partially but significantly attenuated by nitroarginine as an
      inhibitor of nitric oxide synthase, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one
      as an inhibitor of guanylyl cyclase, or by the denudation of endothelial cells.
      In specimens without endothelium, the phenylephrine-induced contraction and
      phosphorylation of myosin light chain (MLC) were significantly attenuated after
      the pretreatment with linalyl acetate. The relaxation caused by linalyl acetate
      in the endothelium-denuded specimens was clearly inhibited by calyculin A as an
      inhibitor of MLC phosphatase, although not by ML-9 as an inhibitor of MLC kinase.
      Furthermore, suppression of the phenylephrine-induced contraction and MLC
      phosphorylation with linalyl acetate was canceled by the pretreatment with
      calyculin A. These results suggest that linalyl acetate relaxes the vascular
      smooth muscle through partially activation of nitric oxide/cyclic guanosine
      monophosphate pathway, and partially MLC dephosphorylation via activating MLC
      phosphatase.

PMID- 16891915
TI  - Benazepril combined with either amlodipine or hydrochlorothiazide is more
      effective than monotherapy for blood pressure control and prevention of end-organ
      injury in hypertensive Dahl rats.
AB  - We studied the effect of hydrochlorothiazide (HCTZ), the angiotensin-converting
      enzyme inhibitor benazepril, the calcium channel blocker amlodipine, or a
      combination of benazepril/amlodipine or benazepril/HCTZ on systolic blood
      pressure (BP) and end-organ injury (left ventricular hypertrophy, proteinuria,
      and endothelium-dependent relaxation to acetylcholine) in hypertensive Dahl salt
      sensitive rats fed either a normal-salt (0.5% NaCl) or high-salt (4% NaCl) diet
      for 6 weeks. Rats fed a high-salt diet developed hypertension and significant end
      organ injury. Monotherapy with HCTZ (75 mg/L in drinking water) or amlodipine (10
      mg/kg/day by gavage) reduced systolic BP and proteinuria; benazepril (40
      mg/kg/day by gavage) decreased proteinuria without significantly lowering
      systolic BP. In rats receiving a high-salt diet, only HCTZ reduced left
      ventricular hypertrophy, whereas endothelium-dependent relaxation was improved by
      amlodipine and benazepril but not by HCTZ. Combining benazepril with either
      amlodipine or HCTZ dramatically reduced systolic BP and end-organ injury. These
      data clearly support clinical studies suggesting that combination therapy is more
      effective than monotherapy for systolic BP control and prevention of end-organ
      injury. Complementary mechanisms of action of agents from different
      antihypertensive classes appear to facilitate the greater benefit on BP and end
      organ injury.

PMID- 16891917
TI  - Polymyalgia rheumatica is the result of synovitis.

PMID- 16891916
TI  - Effect of nebivolol on endothelial nitric oxide and peroxynitrite release in
      hypertensive animals: Role of antioxidant activity.
AB  - We tested the activity of nebivolol, a beta1-selective blocker with respect to
      nitric oxide (NO) and peroxynitrite (ONOO) generation in the endothelium of
      normotensive Wistar Kyoto (WKY rats) and spontaneously hypertensive rats (SHR).
      The endothelial effects of nebivolol and its 2 optical enantiomers were
      correlated with its antioxidant activity and compared to another beta-blocker,
      atenolol, and 2 agonists of nitric oxide synthase (eNOS), calcium ionophore (CI)
      and acetylcholine (ACh). The effects of nebivolol on the bioavailability of NO
      and ONOO, indicators of endothelial function and dysfunction, respectively, were
      measured in vitro using nanosensors placed in mesenteric arteries. Compared with
      WKY rats, treatment of SHR vessels either with ACh (1 micromol/L) or CI (1
      micromol/L) showed marked deficiencies (>40%, P < 0.01) in bioavailable NO
      concomitant with increased ONOO levels (>50%, P < 0.01). The [NO]/[ONOO] ratio
      measured after stimulation with CI was 2.77 +/- 0.05 in WKY rats and much lower
      (1.14 +/- 0.11) in SHR indicating significant eNOS uncoupling and endothelial
      dysfunction in hypertensive animals. Treatment with nebivolol (10 micromol/L)
      inhibited eNOS uncoupling and reduced endothelial dysfunction in SHR, as
      evidenced by an increase in the [NO]/[ONOO] ratio to 3.09 +/- 0.04. The basis for
      nebivolol activity is attributed to its unique membrane interactions as
      determined by small-angle x-ray diffraction, as well as its antioxidant activity
      at nanomolar to micromolar levels. The antioxidant effects of nebivolol and its
      enantiomers were not reproduced by atenolol. These results demonstrate that
      nebivolol inhibits endothelial dysfunction through a potent antioxidant mechanism
      attributed to its physicochemical interactions with the membrane, independent of
      beta1-blockade activity.

PMID- 16891918
TI  - Peripheral musculoskeletal manifestations in polymyalgia rheumatica.
AB  - OBJECTIVES: The objectives of this study were to evaluate the frequency and
      characteristics of the peripheral musculoskeletal manifestations in polymyalgia
      rheumatica (PMR), evaluate if PMR with peripheral synovitis represents a subset
      with a more severe disease, and examine for clinical and laboratory
      characteristics at onset of PMR that might later predict rheumatoid arthritis
      (RA). PATIENTS AND METHODS: Patients were diagnosed with PMR according to the
      1982 Chuang criteria. Patients were followed up between 1990 and 2002. The
      following musculoskeletal manifestations at onset and during the follow up were
      considered: peripheral synovitis, distal extremity swelling with pitting edema,
      carpal tunnel syndrome, and distal tenosynovitis. RESULTS: Thirty-eight of the 74
      patients (51%) showed distal musculoskeletal symptoms: 29 (39%) had peripheral
      synovitis, 4 (5%) presented pitting edema, 4 (5%) experienced carpal tunnel
      syndrome, and one (1.3%) had distal tenosynovitis. These manifestations resolved
      completely after corticosteroid therapy was initiated. Peripheral synovitis was
      oligoarticular and often transient. The joints most frequently involved were the
      wrist, metacarpophalangeal, and knee. Erythrocyte sedimentation rate (ESR) was
      normal in 7 patients. When comparing patients with PMR with and without
      peripheral synovitis, no statistically significant differences were found in the
      studied variables. Through the first year of follow up, 7 patients fulfilled the
      American College of Rheumatology 1987 criteria for RA, 2 patients developed giant
      cell arteritis, and 3 had associated malignancy. Patients who developed RA had
      statistically significantly increased presence of persistent synovitis and a
      smaller decrease in mean ESR after treatment with corticosteroids. CONCLUSION:
      Fifty-one percent of the patients with PMR presented distal musculoskeletal
      manifestations, with peripheral synovitis being the most frequent one. Patients
      with PMR with peripheral synovitis did not represent a high-risk subgroup with
      more severe disease. Seven patients who developed criteria for seronegative RA
      within the first year of follow up had presented statistically significant
      persistent synovitis compared with those who continued as PMR and also showed a
      smaller initial decrease in mean ESR after steroid treatment was initiated. The
      absence of persistent arthritis and the benign course of the arthritis permit the
      distinction of PMR from other inflammatory arthropathies.

PMID- 16891919
TI  - Role of anticyclic citrullinated peptide in the diagnosis of early rheumatoid
      factor-negative suspected rheumatoid arthritis: is it worthwhile to order the
      test?
AB  - BACKGROUND: Anticyclic citrullinated peptide (anti-CCP) is a relatively new
      serologic marker, which has been proposed for use in the diagnosis of rheumatoid
      arthritis (RA) and is said to be a highly specific. OBJECTIVE: The aim of the
      study was to evaluate the role of anti-CCP in a South Indian population of
      patients with suspected RA in the early stages when rheumatoid factor is negative
      and clinical presentation is atypical. METHODS: Patients with early inflammatory
      arthritis who were rheumatoid factor-negative were investigated for anti-CCP. The
      patients were reviewed by a rheumatologist and, based on American College of
      Rheumatology criteria, were diagnosed with RA or another disease after a follow
      up period of 3 to 6 months. The rheumatologist was blinded to the results of the
      anti-CCP. The sensitivity and specificity of anti-CCP was estimated in comparison
      to follow up and final clinical diagnosis. The anti-CCP was estimated by the
      enzyme-linked immunosorbent assay method using a commercially available kit
      (Euroimmune). RESULTS: One hundred forty-three patients with a mean age of 47.1
      years and a male to female ratio of 0.22:1 were recruited for the study. Thirty
      cases were positive for anti-CCP and 41 cases were finally diagnosed RA. Twenty
      six of the 30 anti-CCP-positive patients were diagnosed with RA. Thus, the
      sensitivity of anti-CCP in our institution for the diagnosis of RA in the early
      stage in a group of rheumatoid factor-negative patients with atypical
      presentation was 63.4% with 36.6% false-negatives and the specificity was 96.1%
      with 3.9% false-positive cases. The positive predictive value of anti-CCP was
      86.7% and the negative predictive value was 86.7%. Kappa statistic of agreement,
      chi McNemar test, indicated anti-CCP to be an efficient test in this study
      population. CONCLUSION: Anti-CCP is a useful and highly specific but not
      absolutely specific or sensitive test to detect RA and supplements rheumatoid
      factor in the presence of a strong clinical suspicion.

PMID- 16891920
TI  - Image-guided corticosteroid injection of calcific tendonitis of gluteus maximus.
AB  - Gluteus maximus tendonitis with its clinical and imaging patterns has been
      described in radiologic, orthopedic, and rheumatology texts and journals. Image
      guided treatment, however, is not a familiar approach and has only been described
      in one case report in the English literature to the best of our knowledge. We
      present 4 patients with calcific tendonitis of the gluteus maximus who presented
      with excruciating pain in the posterior upper thigh with limitation of daily
      activities. The diagnosis was based on the characteristic radiologic appearances
      of calcifications in the tendon with cortical bone erosion and muscle edema.
      Treatment was with image-guided (fluoroscopy or computed tomography) injection of
      a local anesthetic and corticosteroid. All patients were pain-free on follow up.

PMID- 16891921
TI  - Shoulder pain in the traumatically injured spinal cord patient: evaluation of
      risk factors and function.
AB  - BACKGROUND: Shoulder pain in individuals with traumatic spinal cord injury (TSCI)
      is common and frequently results in chronic debilitating pain recalcitrant to
      treatment. OBJECTIVE: Our objectives were to identify the risk factors associated
      with shoulder pain in the TSCI population. METHODS: A telephone survey and
      medical record review were conducted on a convenience sample of patients with
      TSCI. Data variables included: Shoulder Pain and Disability Index (SPADI),
      demographics, injury type, treatment histories for shoulder pain/dysfunction,
      assistive device use, and radiographic imaging. RESULTS: Respondents (n=63) were
      male (96%) and tetraplegia (51%) with a mean age of 58.1 years. The majority of
      patients (70%) currently had shoulder pain, one third had previous injury to the
      shoulder, and 52% reported bilateral pain. Tetraplegics had higher prevalence
      (80%) of shoulder pain and higher total SPADI scores than paraplegics (P=0.001).
      Previous shoulder trauma increased the likelihood of shoulder pain. Self-care
      posed their most difficult task. Use of a manual wheelchair (71%) and/or trapeze
      bar (51%) was common. However, no differences were found in wheelchair or trapeze
      bar use or average body mass index between groups with and without pain.
      Respondents with pain tended to use trapeze bars less. Of the respondents
      reporting shoulder pain, an estimated 57% received physical therapy and massage
      with most reporting some benefit; 53% had pharmaceutical treatment with variable
      effect. CONCLUSION: Shoulder pain is common in patients with TSCI. Tetraplegics
      fared worse than paraplegics. Pain may limit transfer because respondents with
      pain used trapeze bars less. Understanding and addressing the factors
      contributing to shoulder pain in this vulnerable population is sorely needed.

PMID- 16891922
TI  - Staphylococcal septic synovitis of the sternoclavicular joint with retrosternal
      extension.
AB  - Bacterial arthritis of the sternoclavicular joint is an uncommon disorder caused
      by a variety of microorganisms. Both Gram-positive and Gram-negative bacteria
      have been identified as etiologies of an acute suppurative arthritis, whereas a
      few other bacteria such as mycobacteria and treponemes have been incriminated in
      chronic disease of the sternoclavicular joint. We recently treated a patient with
      staphylococcal synovitis of the sternoclavicular joint, which is the 24th
      recorded in the literature. His illness was complicated by a retrosternal
      abscess, soft tissue abscess of the chest, septic bursitis, and lumbosacral
      discitis. He recovered after 6 weeks of nafcillin therapy without any residual
      infection. Six previous patients with extension into the substernal space and
      mediastinum have been described. Staphylococcal infection of the sternoclavicular
      joint, although usually confined to the joint, can be associated with sepsis and
      metastatic abscess formation as well as substernal extension even in
      immunocompetent individuals.

PMID- 16891923
TI  - Panniculitis: an unusual cutaneous manifestation of rheumatoid arthritis.
AB  - Specific and nonspecific panniculitis may occur during the course of connective
      tissue diseases. However, association of panniculitis and rheumatoid arthritis
      has only rarely been described, and with so few reports, it is difficult to know
      the significance of this unusual association. We describe 2 patients with
      rheumatoid arthritis and features of Sjogren syndrome in whom panniculitis
      developed during the course of the disease. Histologic confirmation of septal
      panniculitis was established in one case and the panniculitis in this case
      improved as the arthritis resolved.

PMID- 16891924
TI  - Chronic destructive elbow arthropathy associated with hydroxyapatite crystals in
      a patient with systemic lupus erythematosus.
AB  - We describe the case of a young woman with systemic lupus erythematosus (SLE) who
      presented with painful acute swelling and limited motion of the elbow. Analysis
      of synovial fluid exhibited a noninflammatory cell count, negative cultures,
      amorphous nonbirefringent particles, and a positive Alizarin red S staining. X
      rays showed calcifications, spurring, sclerosis, and despite the short duration
      of symptoms, loss of radial-humeral and cubital-humeral joint spaces. The
      diagnosis of an acute attack within a chronic degenerative arthropathy of the
      elbow associated with hydroxyapatite crystals was established. Such crystal
      induced arthropathy can be an occasional explanation for acute arthritis in SLE.

PMID- 16891926
TI  - Polymyalgia rheumatica and breast cancer.
AB  - Polymyalgia rheumatica is infrequently the initial manifestation of underlying
      malignancy. A patient is described with infiltrating ductal carcinoma of the
      breast presenting with left breast mass and polymyalgia rheumatica (PMR)-like
      symptoms. Physicians should consider an associated malignancy in PMR when
      patients present with atypical features such as young age, modest elevation of
      the sedimentation rate, and incomplete response to corticosteroids.

PMID- 16891925
TI  - Recurrent postpartum episodic rheumatoid arthritis.
AB  - It is well known that rheumatoid arthritis improves in the majority of patients
      during pregnancy and that aggravation of disease symptoms occurs within the first
      6 months postpartum. We report a female patient who had 4 postpartum episodes of
      transient polyarthritis typical of rheumatoid arthritis with positive serum
      rheumatoid factor and anti-CCP antibodies. All bouts resolved within 4 to 10
      weeks after onset without any symptoms in between the episodes.

PMID- 16891927
TI  - Fibroblastic rheumatism.
AB  - We report the first known South African case of fibroblastic rheumatism, a rare
      dermatoarthropathy. Our patient presented with the typical clinical features of a
      sudden-onset, erosive polyarthritis with cutaneous nodules and sclerodactyly.
      Significant functional loss occurred within a period of 3 to 4 months. X-rays of
      the hands showed a single erosion, whereas magnetic resonance imaging showed
      further erosions as well as soft tissue and synovial enhancement. The unique
      histologic findings of fibroblastic proliferation, thickened collagen, and dermal
      fibrosis confirmed the diagnosis of fibroblastic rheumatism. Our patient was
      treated with a combination of methotrexate and oral prednisolone with subsequent
      resolution of her synovitis/arthritis and no further progression of her
      sclerodactyly and associated functional loss. The course of fibroblastic
      rheumatism is known to vary and although multiple therapeutic options have been
      tried, the question remains whether any of the therapies alters the natural
      course of the disease. However, considering the probable role of lymphocytes and
      fibrogenic cytokines, an increased awareness with early diagnosis and treatment
      in the initial inflammatory stage may prevent the development of incapacitating
      joint sequelae.

PMID- 16891928
TI  - Calcification of medial collateral ligament of the knee: an uncommon cause of
      medial knee pain.

PMID- 16891930
TI  - Basic science for the clinician 39: NF-kappaB-function, activation, control, and
      consequences.
AB  - Were there to be a crossroads through which all inflammatory signaling passed,
      controlling that junction would provide the ultimate therapeutic target for
      rheumatoid arthritis and many, if not all, autoimmune diseases. It now seems
      likely that no single cytokine or cytokine family represents such a crucial
      nexus. However, there is reason to believe that there may be an intracellular
      bottleneck that does: the family of NF-kappaB proteins. This family of proteins
      allows cytokine-receptor signals to enter the nucleus and either enhance or
      suppress the transcription of many genes involved in inflammation and in cellular
      survival itself. The same set of proteins is also involved in apoptosis and
      likely in carcinogenesis. The delicate choreography of control systems, balancing
      the effects of NF-kappaB proteins on the multiple DNA sites that are targeted, is
      also a prime target for specific therapies. Moreover, the NF-kappaB system
      interdigitates with other intracellular systems, eg, kinases, ubiquitin
      associated protein degradation, that are critical to the normal function of
      cells, involved in homeostasis and inflammation, in autoimmune diseases and
      malignancy.

PMID- 16891931
TI  - Recurrent subarachnoid hemorrhage in a 17 year old with wegener granulomatosis.

PMID- 16891932
TI  - Clinical research: a primer of practical tips.

PMID- 16891933
TI  - Celiac disease in a young woman with Takayasu arteritis.

PMID- 16891934
TI  - Acute polyarthritis after bacilli Calmette-Guerin intravesical therapy for
      bladder carcinoma.

PMID- 16891935
TI  - Decompression and lumbopelvic fixation for sacral fracture-dislocations with
      spino-pelvic dissociation.
AB  - PURPOSE: To report results of sacral decompression and lumbopelvic fixation in
      neurologically impaired patients with highly displaced, comminuted sacral
      fracture-dislocations resulting in spino-pelvic dissociation. DESIGN:
      Retrospective clinical study. SETTING: Regional level one trauma center.
      PATIENTS: Nineteen patients with highly displaced, comminuted, irreducible Roy
      Camille type 2-4 sacral fractures with spino-pelvic instability patterns and
      cauda equina deficits were identified over a 6-year period, 18 of which met the
      12-month minimum follow-up criterion. INTERVENTION: All were treated with open
      reduction, sacral decompression, and lumbopelvic fixation. Radiographic and
      clinical results were evaluated. Neurological outcome was measured by Gibbons'
      criteria. MAIN OUTCOME MEASUREMENTS: Radiographic evaluation with computed
      tomography scan and antero-posterior, lateral, and oblique views of the pelvis to
      assess alignment, hardware position and decompression. Clinical evaluation
      emphasizing neurological outcome as described by Gibbons' criteria. RESULTS:
      Sacral fractures healed in all 18 patients without loss of reduction. Average
      sacral kyphosis improved from 43 to 21 degrees. Fifteen patients (83%) had full
      or partial recovery of bowel and bladder deficits, although only 10 patients
      (56%) had improved Gibbons scores. Average Gibbons score improved from 4 to 2.8
      at 31-month average follow-up (range: 12 to 57 mo). Wound infection (16%) was the
      most common complication. Complete recovery of cauda equina function was more
      likely in patients with continuity of all sacral roots (86% vs. 0%, P = 0.00037)
      and incomplete deficits (100% vs. 20%, P = 0.024). Although not statistically
      significant, recovery of bowel and bladder function specifically was more closely
      associated with absence of any sacral root discontinuity (86% vs. 36%, P = 0.066)
      than on completeness of the injury (100% vs. 47%, P = 0.21). CONCLUSIONS:
      Lumbopelvic fixation provided reliable fracture stability and allowed consistent
      fracture union without loss of alignment. Neurological outcome was, in part,
      influenced by completeness of injury and presence of sacral root disruption.

PMID- 16891936
TI  - Noninvasive measurements of intramuscular pressure using pulsed phase-locked loop
      ultrasound for detecting compartment syndromes: a preliminary report.
AB  - OBJECTIVES: To develop a human model for compartment tamponade and test the
      efficacy of ultrasonic pulsed phase-locked loop (PPLL) fascial displacement
      waveform analysis for noninvasive measurement of intramuscular pressure (IMP).
      DESIGN: Human subject experiment. SETTING: University Level 1 trauma center.
      PARTICIPANTS: Nine male and 1 female volunteers (age 20 to 59),3 male acute
      compartment syndrome (ACS) patients (age 31 to 38). INTERVENTION: Thigh
      tourniquet was inflated in a stepwise fashion from 40 to 100 mm Hg to increase
      IMP transiently in volunteers. MAIN OUTCOME MEASUREMENTS: Invasive IMP by slit
      catheter and PPLL fascial displacement waveform in volunteers with model ACS and
      patients with ACS. RESULTS: In the model compartment tamponade group, thigh cuff
      occlusion increased IMP in the anterior compartment from a mean of 12.1 mm Hg (SE
      = 1.5) to a mean of 27.4 mm Hg (SE = 2.4, N = 8, P < 0.0001). By fast Fourier
      transform, the ratio of the amplitude of the fundamental frequency to the
      amplitude of the second harmonic frequency of the fascial displacement waveform
      as measured by PPLL increased from a resting mean of 1.12 (SE = 0.07) to a mean
      of 1.85 (SE = 0.18) under the same protocol (N = 6, P = 0.001). Combined data
      with compartment syndrome patients revealed linear correlation between IMP and
      PPLL with an R value of 0.8887. CONCLUSIONS: Subarterial thigh cuff pressure
      causes a significant and transient increase in IMP, serving as a model for
      anterior compartment tamponade. PPLL is able to detect fascial displacement
      waveforms corresponding to arterial pulsation and furthermore distinguishes
      between normal and elevated IMP. There is a linear correlation between PPLL
      measurements and invasive IMP. The PPLL shows potential utility as a device for
      noninvasive measurement of IMP for detecting compartment syndromes.

PMID- 16891937
TI  - Intra-articular calcaneal fractures treated nonoperatively and followed
      sequentially for 2 decades.
AB  - OBJECTIVE: To assess the sequential and long-term patient outcome after
      nonoperative treatment of a displaced intra-articular calcaneal fracture, and to
      determine if initial results remain stable or deteriorate in the second decade
      after the injury. DESIGN: Retrospective case series with sequential follow-up at
      2 time points a decade apart. SETTING: University teaching hospital. MAIN OUTCOME
      MEASURES: At the first follow-up in 1990, hind feet were assessed with a
      computerized tomographic (CT) scan, radiographs, and with a 100 point score, the
      Iowa calcaneal score (ICS). At the second follow-up in 2000, the ICS was repeated
      and the patients completed the visual analog scale and the SF-36 questionnaire.
      RESULTS: In 1990, 15 of 24 hind feet had good or excellent results on the ICS.
      Sixteen of 19 patients returned to their preinjury level of employment. Subtalar
      arthrosis on the CT scan correlated with lower average scores [64 points vs. 82
      points (P < 0.035)]. Ten years later in 2000, the average ICS had decreased from
      74 points to 64 points (P < 0.03); however, in patients with no or minimal
      arthrosis detected on the 1990 CT scan, the scores remained stable with an
      average of 82 points, in 1990, and an average of 81 points in 2000 (P < 0.61).
      SUMMARY: These results suggest that after nonoperative treatment of closed
      displaced intra-articular calcaneus fractures, clinical results correlate with
      the presence of subtalar arthrosis on CT scans [except for those with grade V
      (spontaneous fusion)]. Patients with arthrosis grades III and IV have increased
      pain and deterioration in function in the second decade after injury compared
      with those with minimal arthrosis (grades I or II) or those who spontaneously
      fused their subtalar joint. Patients without arthrosis have good outcomes that
      remained stable over greater than 2 decades of follow-up.

PMID- 16891938
TI  - The effect of levodopa or levodopa-carbidopa (sinemet) on fracture healing.
AB  - OBJECTIVES: Levodopa (L-dopa) and L-dopa/carbidopa were evaluated to determine
      their effectiveness in the stimulation of bone healing of fractures at risk for
      nonunions. METHODS: Forty-two retired breeder female Sprague-Dawley rats were
      divided into 2 experimental groups and 1 control. Thirty-six rats were evaluated
      for results. The right femur of each rat was fractured and an intramedullary
      omega pin was inserted to create a 2 mm bone gap. The rats were administered
      either 0.2 g/kg/d of L-dopa, 0.2/0.02 g/kg/d L-dopa/carbidopa in their feed, or
      plain powdered chow (Sham control group). The rats were killed at 5 weeks
      postsurgery. The femurs were excised, radiographed, and mechanically tested. Bone
      healing was assessed. Bone stiffness, ultimate load, and energy to failure were
      determined under 3 point bending using an Instron materials testing system.
      RESULTS: The femurs of 30% of the Sham rats healed compared with 50% of the L
      dopa/carbidopa and 84% of the L-dopa treated femurs. The healed L-dopa rat femurs
      had significantly greater ultimate load (P = 0.037) and energy to failure (P =
      0.004) than the healed Sham rats. There were no significant differences between
      the L-dopa/carbidopa group and either the Sham or L-dopa group. CONCLUSIONS:
      These results confirm that L-dopa administration increases the healing in
      nonunion fractures. The combination of L-dopa/carbidopa did not significantly
      increase fracture healing.

PMID- 16891939
TI  - Bacterial adherence to tantalum versus commonly used orthopedic metallic implant
      materials.
AB  - OBJECTIVES: Evaluation of bacterial adhesion to pure tantalum and tantalum-coated
      stainless steel versus commercially pure titanium, titanium alloy (Ti-6Al-4V),
      and grit-blasted and polished stainless steel. DESIGN: Experimental in vitro cell
      culture study using Staphylococcus aureus and Staphylococcus epidermidis to
      evaluate qualitatively and quantitatively bacterial adherence to metallic
      implants. METHODS: A bacterial adhesion assay was performed by culturing S.
      aureus (ATCC 6538) and S. epidermidis (clinical isolate) for one hour with
      tantalum, tantalum-coated stainless steel, titanium, titanium alloy, grit-blasted
      and polished stainless steel metallic implant discs. Adhered living and dead
      bacteria were stained using a 2-color fluorescence assay. Adherence was then
      quantitatively evaluated by fluorescence microscopy and digital image processing.
      Qualitative adherence of the bacteria was analyzed with a scanning electron
      microscope. The quantitative data were related to the implant surface roughness
      (Pa-value) as measured by confocal laser scanning microscopy. RESULTS: Bacterial
      adherence of S. aureus varied significantly (p = 0.0035) with the type of
      metallic implant. Pure tantalum presented with significantly (p < 0.05) lower S.
      aureus adhesion compared to titanium alloy, polished stainless steel, and
      tantalum-coated stainless steel. Furthermore, pure tantalum had a lower, though
      not significantly, adhesion than commercially pure titanium and grit-blasted
      stainless steel. Additionally, there was a significantly higher S. aureus
      adherence to titanium alloy than to commercially pure titanium (p = 0.014). S.
      epidermidis adherence was not significantly different among the tested materials.
      There was no statistically significant correlation between bacterial adherence
      and surface roughness of the tested implants. CONCLUSIONS: Pure tantalum presents
      with a lower or similar S. aureus and S. epidermidis adhesion when compared with
      commonly used materials in orthopedic implants. CLINICAL IMPLICATION: Because
      bacterial adhesion is an important predisposing factor in the development of
      clinical implant infection, tantalum may offer benefits as an adjunct or
      alternative material compared with current materials commonly used for orthopedic
      implants.

PMID- 16891940
TI  - Valgus osteotomy of the proximal femur with sliding hip screw for the treatment
      of femoral neck nonunions: the technique, a case series, and literature review.
AB  - Femoral neck nonunions are a difficult complication in the treatment of femoral
      neck fractures and have traditionally been managed using an intertrochanteric
      valgus osteotomy and blade plate. We propose an alternative method, a proximal
      femoral valgus osteotomy using a sliding hip screw instead of a blade plate. This
      technique eliminates many of the difficulties experienced with the valgus
      osteotomy and blade plate by employing a device and instrumentation that is more
      familiar to orthopedic surgeons. The technique is reproducible and has been used
      successfully in a series of 4 patients.

PMID- 16891941
TI  - Removal of a broken intramedullary nail with a narrow hollow.
AB  - This report describes a technique for removal of a broken interlocking
      intramedullary nail with a small diameter and narrow hollow using a modified
      smooth guide wire.

PMID- 16891942
TI  - Free fibula and corticocancellous bone grafting for salvage of a war-injured
      forearm.
AB  - The treatment of a complex forearm injury inflicted by a wartime mine explosion
      is presented in this study. Apart from the soft tissue damage, a 4-part fracture
      of the radius and loss of 19 cm of the ulnar diaphysis were present along with
      lesions of the median and ulnar nerves. The radial pulse was intact. The first
      formal treatment of the wounding consisted of extensive soft tissue and bone
      debridement and external fixation of radius with an additional intramedullary K
      wire. After wound closure was obtained, a free vascular fibula grafting of the
      ulna and corticocancellous bone grafting of the radius were performed. Bone union
      of both the radius and ulna was subsequently achieved and 9 years after the
      injury, the patient has full flexion and extension of the elbow, full pronation
      and 70% of supination. Motion of the wrist is limited because of an ulnar plus
      variant of the distal radioulnar joint. Hand function is still limited by chronic
      low-moderate median nerve palsy, but the ulnar nerve has recovered completely.
      The patient is able to pinch, has full finger extension and can make a fist. He
      is satisfied that he made the correct decision in not having an initial
      amputation for his injury.

PMID- 16891943
TI  - Treatment of bilateral elbow dislocation using external fixation with motion
      capacity: a report of 2 cases.
AB  - Bilateral elbow dislocation is a rare injury and only 11 cases are described in
      the literature, including 8 patients with isolated ligamentous and 3 patients
      with an additional osseous injury. We present 2 cases of bilateral posterior
      elbow dislocations treated with a bilateral hinged elbow fixator with motion
      capacity to allow for early physiotherapy. Both patients had a high-energy trauma
      with one who fell off a ladder from a 5 m height and the second from a mountain
      bike injury during off-road biking. All extremities were neurovascularly intact.
      In the operating room, severe instability was detected in all 4 elbows: after
      closed reduction in 3 elbows and open reduction in 1 elbow for a Mason type 4
      fracture of the radial head that was internally fixed using fine threaded
      implants, an elbow fixator with motion capacity was applied in all 4 elbows for a
      period of 6 weeks. One year after surgery, the active range of motion was
      0/10/140 degrees of extension and flexion on the right and 0/0/130 degrees on the
      left side. The second patient achieved 0/0/125 degrees and 0/10/130,
      respectively. Pro- and supination was full in both patients. All 4 elbows were
      stable and there were no radiologic signs of degenerative changes at the 1 year
      follow-up. Treatment of bilateral elbow dislocation using external fixation with
      early motion capacity allows for active physiotherapy although maintaining joint
      stability, thus minimizing complications normally associated with the injury.
      Using this method resulted in an excellent clinical outcome for both patients.

PMID- 16891944
TI  - High-pressure injection injuries to the upper extremity: a review of the
      literature.
AB  - OBJECTIVES: The purpose of this review was to identify the relative impact of
      injected material, location of injury, time to debridement, injection pressure,
      infection, and the use of adjuvant steroid medication upon the need for
      amputation after high-pressure injection injuries to the upper extremity. DATA
      SOURCES AND STUDY SELECTION: A Medline literature search extending from 1966 to
      December 2003 was performed, referencing the key words "high-pressure injection
      injury," "grease gun injury," "paint gun injury," "pressure gun injury," and
      "high-pressure injection." The results were limited to the English language and
      to reports involving human subjects. Each abstract was reviewed to confirm that
      the described injury had occurred in the upper extremity and that it had truly
      been a high-pressure injection. The reference pages from each of the papers were
      reviewed to identify additional reports of high-pressure injection injury.
      Manuscripts describing injuries resulting from hand held syringes or other low
      pressure mechanisms were excluded. DATA EXTRACTION: All of the manuscripts were
      analyzed to identify the clinical outcome, age, hand dominance, site of
      injection, substance injected, injection pressure, elapsed time to wide
      debridement, use of steroids, and incidence of infection. These variables were
      subjected to a Pearson chi test to determine their impact upon the need for
      amputation. RESULTS: Four hundred thirty-five cases of high-pressure injection
      injury to the upper extremity were identified. The amputation rate after these
      injuries was 30%. The location of the injury and the material injected
      contributed significantly to the need for amputation. For injections of paint,
      paint thinner, gasoline, oil, or jet fuel (organic solvents), the amputation risk
      was lower if wide surgical debridement occurred within 6 hours of injury.
      Steroids did not impact the amputation rate or incidence of infection. The
      presence of infection did not affect the incidence of amputation. CONCLUSIONS:
      The risk of amputation after high-pressure injection injury to the upper
      extremity is highest with organic solvent injection into the fingers. Injections
      into the thumb or palm result in a much lower frequency of tissue loss. Emergent
      surgical debridement reduces the amputation risk after injections of organic
      solvents. From the available data, no conclusions could be reached regarding
      functional outcomes, other than amputation, after high-pressure injection injury.

PMID- 16891945
TI  - Submitted by Timothy Bhattacharyya, MD, Massachusetts General Hospital,
      Orthopaedic Associates, 55 Fruit Street, YAW 3C, Boston, MA.

PMID- 16891946
TI  - Management of displaced ankle fractures.
AB  - BACKGROUND: Ankle fractures excluding pilon fractures, account for approximately
      9% of all fractures with the majority being OTA type B injuries. Although
      surgeons generally treat undisplaced or minimally displaced injuries
      nonoperatively and displaced fractures operatively, opinions diverge regarding
      the management of those displaced fractures with acceptable closed reduction.
      There is also debate about the use of biodegradable implants in operatively
      managed ankle fractures, the type and technique of fixation for operatively
      treated syndesmotic injuries as well as the approach to postoperative
      rehabilitation. OBJECTIVE: We aimed to review the highest level of available
      evidence on the operative management of ankle fractures. We focused specifically
      on studies comparing (1) nonoperative versus operative management of displaced
      ankle fractures, (2) biodegradable versus metal implants, (3) syndesmotic
      fixation, and (4) postoperative rehabilitation protocols.

PMID- 16891948
TI  - Comment: does fibular plating improve alignment...

PMID- 16891955
TI  - Effect of growth velocity on the progression of adolescent idiopathic scoliosis
      in boys.
AB  - Growth velocities, curve magnitudes, curve patterns and Risser signs of 80
      consecutive untreated boys with adolescent idiopathic scoliosis were studied
      retrospectively and compared with the progression velocity of the curves. Growth
      velocity >or=4 cm/year with curves >or=25 degrees increased progression velocity
      of curves significantly (P<0.001). Growth velocity was fastest at skeletal ages
      12-13 years but continued moderately after the age of 16 years. The major right
      thoracic curves were the most progressive.

PMID- 16891956
TI  - Solitary spinal eosinophilic granuloma in children.
AB  - Solitary vertebral eosinophilic granuloma is said to be a rare spinal condition
      in children. 'Vertebra plana' is considered as the typical radiological feature
      of the involved vertebra; but it could be observed only in 40% of the patients.
      We have studied three pediatric patients with solitary vertebral eosinophilic
      granuloma. Their complaint was pain and/or stiffness of the back. Two of them
      developed neurological deficits in their lower limbs. The diagnosis in imaging
      (plain radiographs, computed tomography scan and magnetic resonance imaging)
      varied from one case to another. Histopathology confirmed the diagnosis of
      eosinophilic granuloma. These three patients underwent an open biopsy and a
      resection of the spinal lesion achieved with or without interfixation. The
      outcome was satisfactory in these three cases after a mean follow-up period of
      over 2 years (from 23 to 27 months).

PMID- 16891958
TI  - Interobserver reliability of the Mallet score.
AB  - The interobserver reliability of the Mallet score for active shoulder function
      was assessed by three experienced observers in a group of 30 children with an
      obstetric brachial plexus lesion (mean age 7.1 years, range 4.5-10 years).
      Interobserver reliability, measured using weighted kappa, was good. Kappa varied
      between 0.37 and 0.84 and differed between the different aspects of the Mallet
      score and different pairs of observers. In decreasing order, mean weighted kappa
      was 0.75 for abduction, 0.73 for hand to neck, 0.67 for hand to spine, 0.6 for
      external rotation and 0.53 for hand to mouth.

PMID- 16891957
TI  - Corrosion and late infection causing delayed paraparesis after spinal
      instrumentation.
AB  - A 28-year-old female patient came to our hospital 14 years after surgical
      correction of adolescent idiopathic scoliosis with a 316L stainless-steel
      instrumentation. She presented progressive paraparesis during the last 2 months.
      Plain radiography, computed tomography scan and computed tomography-scan-guided
      needle biopsy revealed that a metallotic mass penetrated into the spinal canal,
      causing compression of the spinal cord at the T5-T6 level. The patient's symptoms
      were related to corrosion of the implant and infection by Propionibacterium
      acnes. Through a posterior approach, the instrumentation was retrieved and the
      metallotic mass and tissues were excised. Six months after the surgery, the
      patient is completely asymptomatic. Corrosion of stainless-steel implants is a
      finding more common than supposed. Biocorrosion--or microbially influenced
      corrosion--is a concept to be taken into account. It is possible that bacteria
      may modify the rate of corrosion of metals. Early diagnosis of corrosion is
      essential in order to prevent cases like the one we report, and perhaps, as
      suggested for total hip arthroplasties, metal levels could be useful to monitor
      spinal implants.

PMID- 16891959
TI  - Radiological evaluation of unstable (acute) slipped capital femoral epiphysis
      treated by pinning with Kirschner wires.
AB  - Treatment of slipped capital femoral epiphysis is still controversial with regard
      to the implants used for stabilization and the need for prophylactic treatment of
      the contralateral, unaffected, side. The objective of this study was to ascertain
      whether prophylactic transfixation of the epiphysis with Kirschner wires in
      patients with unstable slipped capital femoral epiphysis resulted in significant
      disturbance of the growth plate and impairment of further growth of the femoral
      neck and head. Between 1990 and 1999, 29 patients with unstable slipped capital
      femoral epiphysis were simultaneously treated with internal fixation of the
      epiphysis and metaphysis with 3-4 Kirschner wires on the affected and the not
      (yet) affected side. After a mean follow-up of 3.5 years, we evaluated the hip
      joints radiologically, analysing different roentgenological parameters (CCD
      angle, femoral head diameter, length of the femoral neck and sphericity of the
      femoral head). CCD angle, femoral head diameter and length of the femoral neck
      showed statistically significant (P<0.001, Student's t-test) differences between
      the affected and unaffected, but prophylactically pinned, sides. Asphericity of
      the femoral head was found in six cases only on the affected side, whereas all
      hips, which were operated prophylactically, showed spherical femoral heads at
      follow-up (P<0.02, Pearson's chi test). These results indicate that the slip
      itself may cause impairment of the femoral growth plate in patients with unstable
      slipped capital femoral epiphysis and not stabilization with Kirschner wires.
      Compared with other series from the literature using different implants (screws,
      nails), prophylactic transfixation of the epiphysis and metaphysis with Kirschner
      wires is less compromising to the growth plate on the not (yet) affected side.

PMID- 16891960
TI  - Windswept hip deformity in children with cerebral palsy.
AB  - Windswept hip deformity describes an abduction and external rotation position of
      one hip with the opposite hip in adduction and internal rotation. Windswept hip
      deformity may occur in association with hip dislocation and scoliosis. We
      analysed the prevalence of this deformity in a total population of children with
      cerebral palsy, and the impact of hip prevention and early treatment of
      contractures on the prevalence and severity of windswept hip deformity. The
      frequency of windswept hip deformity was 12% in the control group and 7% in the
      study group, comprising children in the hip prevention programme. The children
      with this deformity in the study group had a lower frequency of scoliosis and
      none had hip dislocation. It thus seems that the hip prevention programme results
      in a decrease in the number of children with windswept hip deformity, and a
      decrease in the severity of the deformity.

PMID- 16891961
TI  - Use of videographic examination for analysis of efficacy of botulinum toxin in
      the lower limbs in children with cerebral palsy.
AB  - The objective of this study was to test the interobserver and intraobserver
      reproducibility of videographic gait analysis in paediatric cerebral palsy
      patients following botulinum toxin type-A injections. Standardized videos
      according to gait-specific functional criteria were assessed for 1 h. For
      intraobserver reproducibility, 13 of 17 items showed good/moderate correlation,
      one mediocre and three poor correlation. For interobserver reproducibility, 12 of
      17 items showed excellent, good or moderate agreement, five items showed poor
      agreement. Overall, 9 of 17 items showed good intraobserver or interobserver
      reproducibility. Mean interobserver scores for sagittal plane items were slightly
      lower than mean intraobserver scores (kappa=0.509 and 0.536, respectively). In
      conclusion, video analysis of children with cerebral palsy based on functional
      criteria is useful.

PMID- 16891962
TI  - Sagittal knee kinematics after hamstring lengthening.
AB  - The purpose of this study was to analyze sagittal knee kinematics after hamstring
      lengthening. A retrospective analysis was performed of 16 children (32 knees)
      with cerebral palsy who underwent hamstring lengthening as an isolated surgical
      procedure. Gait analysis was performed before surgery and at a minimum of 1 year
      after surgery. Decreased stance maximum knee flexion, stance minimum knee
      flexion, swing maximum knee flexion, and swing minimum knee flexion were noted.
      Total knee excursion increased. The present study confirmed the previously
      reported increased total knee excursion with decreased stance minimum and swing
      maximum knee flexion.

PMID- 16891963
TI  - Optimal injection points for the neuromuscular blockade of forearm flexor
      muscles: a cadaveric study.
AB  - Botulinum toxin acts at neuromuscular junctions close to muscle motor points and
      is used to help manage spastic upper-limb deformities. To develop a system
      allowing clinicians to identify optimal injection sites by an easily reproducible
      technique, forearm flexor muscles were dissected in 20 formalin-preserved human
      limbs. Motor points for flexor carpi ulnaris, flexor carpi radialis, flexor
      digitorum superficialis and pronator teres were (1) identified, (2) related to a
      reference grid based on lines (proximal, distal, lateral, medial and diagonals)
      drawn between forearm anatomical landmarks, and (3) defined in terms of their
      percentage distances along the established grid lines.

PMID- 16891964
TI  - Lipoblastoma and lipoblastomatosis.
AB  - We report two cases of lipoblastoma of the buttock in a 10-month-old boy and a 20
      month-old girl, the first with rearrangement of chromosome 8 and the second
      without cytogenetic abnormality, and one case of lipoblastomatosis of a leg in a
      6-month-old boy with a normal karyotype but with a rearrangement of the PLAG1
      gene. Lipoblastoma and lipoblastomatosis are two different presentation of the
      same rare benign soft tissue mesenchymal tumour arising from fetal white fat and
      occurring almost exclusively in young children under 3 years. These neoplasms
      have no malignant potential but may recur in cases of incomplete resection.
      Histological diagnosis sometimes used to be difficult because of the close
      resemblance of the lesion with myxoid liposarcoma. Nowadays, cytogenetic analysis
      may contribute to the diagnosis by showing abnormalities of the long arm of
      chromosome 8, leading to rearrangement of the PLAG1 gene. Actual advances in
      cytogenetic molecular analysis may aid in accurate diagnosis.

PMID- 16891965
TI  - Elevation of medial tibial condyle for severe tibia vara.
AB  - Clinical and radiological evidence of knee instability was used as criteria for
      elevation of medial tibial condyle in severe tibia vara. Restoration of tension
      to the exposed medial collateral ligament was used as a guide for the required
      amount of elevation. A second-stage proximal tibial osteotomy was performed later
      for correction of the remaining varus deformity. External fixators were used in
      all instances. Elevation of the medial tibial condyle is indicated in severe
      tibia vara with arrest of the medial tibial physis, in which more than a 10
      degrees difference exists between valgus and varus stress radiographs with the
      knee in extension as compared with an opposite normal knee.

PMID- 16891966
TI  - Biomechanical comparison of flexible intramedullary nailing versus crossed
      Kirschner wire fixation in a canine model of pediatric forearm fractures.
AB  - This study compares the biomechanical properties of crossed Kirschner wires with
      those of flexible intramedullary nails in a canine model. The Kirschner wire
      groups had greater anteroposterior, lateral, and torsional stiffness and force to
      failure rates in most of the bones tested. Bones fixated with flexible
      intramedullary nails could bend and recoil during failure testing. The bones
      fixated with Kirschner wires failed at smaller levels of displacement and
      frequently had hardware cut-out during failure testing. Flexible intramedullary
      nails have more recoil and do not induce new fracture lines, which may explain
      their clinical superiority to Kirschner wires despite providing less rigid
      fixation.

PMID- 16891967
TI  - A specific closed percutaneous technique for reduction of Jeffery type II lesion.
AB  - Open reduction is commonly recommended in Jeffery type II fractures. Attempts to
      reduce these fractures percutaneously were reported as unsafe and unreliable. We
      revisited this technique and used a specific percutaneous reduction that turned
      out to be successful in two cases. Instead of lifting the radial head as
      described in leverage maneuver, we use a pushing-back procedure to reduce the
      fracture. The maneuver aims at suppressing the capitellum interposition between
      the head fragment and the metaphysis by reproducing the reversed trajectory of
      trauma. This reduction is made possible because of the posterior periosteal
      attachment of the radial head. A few weeks after the procedure, the two patients
      remained painless, recovered a complete range of motion in prono-supination and
      returned to sports. In these two cases, the procedure used led to a prompt
      recovery and provided a much better outcome than described with the classic open
      approach.

PMID- 16891968
TI  - A novel elastic exsanguination tourniquet as an alternative to the pneumatic cuff
      in pediatric orthopedic limb surgery.
AB  - We describe our experience with a novel surgical exsanguination tourniquet (S
      MART; OHK Medical Devices, Haifa, Israel) in clinical pediatric orthopedics. We
      evaluated the surgical exsanguination tourniquet's properties and clinical use in
      51 patients and compared our observations with our long-standing experience with
      the Esmarch bandage, pneumatic tourniquet and sterile stockinet. Using the
      surgical exsanguination tourniquet, we found superior exsanguination quality,
      quick application and the ability to place the occlusion ring closer to the
      surgical field. No side effects or ischemic complications were observed. After
      removal, the skin under the ring was intact in all cases. We conclude that the
      surgical exsanguination tourniquet is safe and valuable in our practice.

PMID- 16891969
TI  - Pink pulseless hand following supra-condylar fractures: an audit of British
      practice.

PMID- 16891970
TI  - Posterior cervical screw placement without image guidance: a safe and reliable
      practice.
AB  - The use of lateral mass screws for posterior cervical fixation has become
      widespread. It allows for stable fixation in the absence of the posterior
      elements and confers immediate stability. Lateral mass fixation has been shown to
      impart equal or greater biomechanical stability when compared to posterior
      interosseous wiring or anterior plating. The utilization of intraoperative
      fluoroscopy to guide screw placement has been recommended previously and is
      considered routine practice in many centers. This prospective study shows that
      lateral mass screws can be safely positioned without intraoperative fluoroscopy.
      The procedure is both safe and effective, provided that the operator has a
      thorough understanding of lateral mass anatomy coupled with careful adherence to
      the established guidelines for screw positioning. Exposure to radiation is
      reduced and time taken for operation can be shortened.

PMID- 16891971
TI  - Risk factors for delayed extubation after single-stage, multi-level anterior
      cervical decompression and posterior fusion.
AB  - Airway difficulties after single-stage, multilevel anterior and posterior
      cervical surgery are potentially life-threatening complications. Although
      extubation delays can occur, overnight intubation can reduce the risk of
      postoperative airway emergencies. Our protocol was as follows: all patients were
      kept intubated overnight in an intensive care unit and examined by the intensive
      care unit staff each morning. Readiness for extubation was based on the cuff-leak
      test, and extubation done on patients beyond the first postoperative day was
      considered delayed. Eleven patients were extubated on the first postoperative day
      (group 1), and 11 extubated beyond day 1 (group 2). No airway emergencies
      occurred. Patient factors-age, weight, smoking, medical comorbidities, American
      Society of Anesthesiologist class-were not significantly related to extubation
      delay. There were no differences between groups in the number of anterior and
      posterior levels or anterior and posterior operative times. Delayed extubation
      was significantly related to total operative time (8.2 hours vs. 10.6 hours),
      volume of crystalloid replacement (3,627 cm3 vs. 6,218 cm3) and intraoperative
      blood transfused (0.7 units vs. 3.1 units); approaching significance was
      increased blood loss (1,238 mL vs. 2,820 mL). We have found intraoperative
      factors-operative time, crystalloid volume, blood loss and replacement-rather
      than patient characteristics, to be risk factors for delayed extubation. Good
      communication with anesthesia staff and careful attention to postoperative airway
      management is essential after single-stage, multilevel anterior cervical
      decompression and posterior fusion.

PMID- 16891972
TI  - Intraoperative technique to define the safe lateral limits of anterior cervical
      corpectomy: a cadaveric study.
AB  - STUDY DESIGN: We describe a surgical radiographic technique during anterior
      cervical corpectomy to define the safe lateral limit of dissection. OBJECTIVE: To
      assess the radiographic technique accuracy using computed tomography (CT)
      measurements on cadaveric specimens. Two clinical cases are presented. SUMMARY OF
      BACKGROUND DATA: During anterior cervical surgery loss of orientation can lead to
      eccentric decompression and vertebral artery injury. METHODS: A two-level
      corpectomy on 4 cadaveric samples was filled with radioopaque dye. An
      "introperative" antero-posterior x-ray was used to measure the narrowest distance
      from dye column to uncovertebral joints. A CT scan confirmed the distance from
      corpectomy to vertebral arteries. RESULTS: The distance between the x-ray dye
      column and uncovertebral joints averaged 2.7 mm (range, 0 to 7+/-2.2 mm). A CT
      scan demonstrated the distance from corpectomy to vertebral artery averaged 4.5
      mm (range, 0 to 10+/-4.4 mm). The measured distance underestimated the true
      distance by an average of 1.8 mm (range, 0 to 8+/-2.2 mm). CONCLUSION: An
      intraoperative radiographic technique can estimate the lateral distance between
      the corpectomy and vertebral arteries by measuring the distance from the dye
      column to uncovertebral joints. The dye radiographic technique provides the
      surgeon an additional margin of safety.

PMID- 16891973
TI  - "Normal" prevertebral soft tissue swelling following elective anterior cervical
      decompression and fusion.
AB  - INTRODUCTION: Prevertebral soft tissue swelling (PSTS) has been evaluated in the
      setting of traumatic cervical spine injuries. However, no study to date has
      quantified the PSTS following elective anterior cervical decompression and fusion
      or the time course to resolution of that swelling. METHODS: From May 2002 to May
      2005 the senior author performed 193 elective 1- or 2-level anterior cervical
      decompression and fusions. Patients who underwent corpectomies and anterior
      cervical fusions for trauma or tumor were excluded. Preoperative, 2-week
      postoperative and 6-week postoperative radiographs were available on 100
      patients. The prevertebral soft tissue stripe was measured on the neutral lateral
      radiographs for the 3 time points. The mean swelling (mm) for each time point was
      calculated and stratified by cervical level. Repeated measures analysis of
      variance with the Tukey-Kramer multiple comparisons test was used to compare the
      measured swelling at the various time points. RESULTS: The average PSTS was
      calculated for each cervical level, for each of the 3 time points, preoperative,
      2- and 6-week postoperative. There was a significant increase in PSTS between the
      preoperative and 2-week postoperative measurements at all levels. There is a
      significant decrease in PSTS between 2- and 6-week postoperatively at all
      cervical levels. There is no significant change in PSTS at C2, C3, and C5, when
      comparing the preoperative and 6-week postoperative measurements. There is
      significant PSTS at C4, C6, and C7, when comparing preoperative and 6-week
      postoperative measurements. CONCLUSIONS: The "normal" range for PSTS at 2 weeks
      and at 6 weeks after elective 1- and 2- level anterior cervical decompression and
      fusions is described. Our data demonstrates that edema persists at the 2-week
      follow-up. By 6 weeks postoperative, the increased PSTS has greatly dissipated.

PMID- 16891974
TI  - Postoperative changes at the lower end of cervical laminoplasty: for preservation
      of the C7 spinous process in laminoplasty.
AB  - INTRODUCTION: C3-C7 laminoplasty has been the standard treatment for cervical
      myelopathy, although several recent reports described C3-C6 laminoplasty for
      preserving the muscles inserting in C7 and reducing postoperative axial symptoms.
      However, postoperative changes at C6/C7 of the lower end of C3-C6 laminoplasty,
      especially regarding a possibility of postoperative spinal canal narrowing have
      not been measured. The purpose of this study was to clarify postoperative changes
      at the lower end of laminoplasty. METHODS: Pre and postoperative spinal dura
      diameter at the lower end of conventional C3-C7 laminoplasty using MRI, and the
      related factors for spinal dura diameter and the causes of postoperative dura
      narrowing were investigated. RESULTS: At the last follow-up after C3-C7
      laminoplasty, dura diameter at C7/T1 was significantly wider after operation than
      before operation, and postoperative narrowing of dura diameter, which was found
      in 20% of patients, was a maximum amount of one millimeter. No pre and
      postoperative factor significantly correlated with dura diameter at C7/T1. The
      causes of postoperative narrowing at the lower end of laminoplasty were disc
      protrusion and/or posterior scar, or segmental angulation of the spinal cord.
      CONCLUSION: In conclusion, the presence of preoperative subarachnoid space over
      one millimeter at C6/C7 may be able to be one of the radiological indications for
      C3-C6 laminoplasty.

PMID- 16891975
TI  - A quantitative analysis of strain at adjacent segments after segmental
      immobilization of the cervical spine.
AB  - STUDY DESIGN: A biomechanical study on human cadaveric cervical spines with
      segmental fixation. OBJECTIVES: To quantify the strains across all segments of
      the spine after simulated fusion. SUMMARY OF BACKGROUND DATA: Clinical evidence
      suggests that degenerative changes occur at adjacent levels after cervical
      fusion. This may, in part be due to increased stress and motion at the adjacent
      segments. MATERIALS AND METHODS: Seven fresh frozen human cervical cadaveric
      spines were used. The spines were mounted onto frames at C2 and C7. Biomechanical
      testing was performed on a modified MTS tester. The specimens were tested in
      rotation control. To simulate fusion, a block was used to replace the disc.
      Fixation was enhanced using an anterior plate and stainless steel wire through
      the spinous processes. Testing was then performed with the same displacement
      magnitudes used for the intact spine. Displacement across 5 disc spaces was
      recorded using extensometers. The same preparation and testing was done for 1, 2,
      and 3-level simulated fusions. All data were normalized to the individual intact
      specimen. RESULTS: After 1-level simulated fusion at C5-6, flexion-extension
      rotation increased by 60% at the superior adjacent level (C4-5) and by 15% at the
      adjacent inferior level (C6-7). Lateral bending increased by 51% at C4-5 and by
      16% at C6-7. Axial rotation increased by 25% at C4-5 and by 200% at C6-7. Flexion
      extension, lateral bending and axial rotation increased at all other segments,
      not only at adjacent segments, after 1, 2 and 3-level fixation. CONCLUSIONS:
      Cervical fusion results in increased strains at adjacent levels, and to all other
      levels, inferiorly and superiorly. This study represents the first to quantify
      the increased strain at all adjacent levels.

PMID- 16891976
TI  - Lumbar total disc replacement using ProDisc II: a prospective study with a 2-year
      minimum follow-up.
AB  - A lumbar total disc replacement (TDR) is believed to be a promising substitute in
      the surgical treatment for lumbar degenerative disc disease. The purpose of this
      study is to report the clinical and radiographic outcomes of 36 consecutive
      patients who underwent lumbar TDR using ProDisc II, and the factors associated
      with a better clinical outcome after a 2-year minimum follow-up. At the time of
      the latest follow-up, the success rate was 94% of 36 patients according to the
      criteria of the US Food and Drug Administration. Of the 10 patients unable to
      work preoperatively, 7 patients returned to work. Moreover, mean score on the
      visual analog scale for low back and leg pain improved significantly from 7.5 and
      4.7 to 3.0 and 1.2, respectively (P<0.001). In addition, mean Oswestry disability
      index scores improved significantly from 69.2 to 21.0 (P<0.001). Mean disc height
      at the operative level increased significantly from 9.0 to 17.6 mm, and mean
      range of motion increased significantly from 9.7 to 12.7 degrees (P<0.01).
      Statistical analysis showed that the factors associated with a better clinical
      outcome were single level, and a higher postoperative segmental ROM at the
      operative level. At a minimum follow-up of 2 years, the lumbar TDR using ProDisc
      II showed excellent clinical and radiographic outcomes without any significant
      complication. However, future efforts need to be directed toward the evaluation
      of a larger number of patients with longer follow-up.

PMID- 16891977
TI  - Use of recombinant human bone morphogenetic protein-2 as an adjunct in
      posterolateral lumbar spine fusion: a prospective CT-scan analysis at one and two
      years.
AB  - INTRODUCTION: This study determines whether recombinant human bone morphogenetic
      protein-2 (rhBMP-2) (12 mg at the rate of 1.5 mg/mL) delivered on an absorbable
      collagen sponge with an added bulking agent can increase posterolateral lumbar
      spine fusion success rates and decrease time for fusion with autogenous bone
      grafts. METHOD: A prospective, single institution, clinical case-matched,
      radiographic, cohort study was undertaken. A total of 52 patients underwent
      posterolateral lumbar arthrodesis with pedicle screw instrumentation. The
      experimental group (n=41) underwent placement of Iliac crest bone graft (ICBG)
      with InFUSE (12 mg/level at the rate of 1.5 mg/mL). The control group (n=11)
      consisted of sex-matched patients, consecutively collected over the same time
      period with an instrumented posterolateral arthrodesis and ICBG placed in the
      intertransverse space. OUTCOME MEASURES: Thin-cut (2 mm) axial, coronal, and
      sagittal reconstructions were blindly evaluated for evidence of bridging bone and
      cortication of the fusion mass by 3 separate reviewers. Fusions were graded and
      an overall score was given to the quality of the fusion mass. RESULTS: Fifty
      patients (ICBG alone n=11; ICBG/rhBMP-2 n=39) were available for CT evaluation at
      2-year follow-up. An overall 97% (68/70 levels; Definite+Probably Fused) fusion
      rate in the rhBMP-2 group was achieved as compared to the 77% fusion rate (17/22
      levels) in the ICBG alone group (P<0.05). In the rhBMP-2 group, 92% of the
      patients (36/39 patients) received an overall excellent subjective fusion rating
      as compared to 27% (3/11) in the control group (P<0.05). There was no computed
      tomographic evidence of soft-tissue ossification, dural ossification, or laminar
      bone regrowth in any patient. CONCLUSIONS: The adjunctive use of rhBMP-2 and ICBG
      seems to be safe and results in significantly larger and more consistent
      posterolateral fusion masses.

PMID- 16891978
TI  - A preliminary study of the efficacy of Beta Tricalcium Phosphate as a bone
      expander for instrumented posterolateral lumbar fusions.
AB  - The associated morbidity of allograft(s) as bone graft expanders in spinal
      surgery has prompted the search for alternatives. The efficacy of Vitoss/Beta
      Tricalcium Phosphate (B-TCP: OrthoVita, Malvern PA, USA), an artificial bone
      substitute, combined with lamina autograft (50:50 mix) in 40 prospective
      posterolateral fusions utilizing pedicle/screw instrumentation was analyzed.
      Multilevel lumbar laminectomies (average 3.7 levels) were accompanied by 1 (27
      patients) and 2 level (13 patients) fusions. Two neuroradiologists independently
      assessed fusion progression on dynamic x-rays and 2D-CT studies performed at 3,
      6, and up to 12 months postoperatively. Outcomes were quantified utilizing Odom
      Criteria and Short-Form 36 (SF-36) questionnaires (preoperatively; and 3, 6, and
      12 months postoperatively). By the sixth postoperative month, fusion was
      neuroradiologically confirmed on both dynamic x-rays and CT studies for 26 of 27
      single level fusions (1 pseudarthrosis), and 11 of 13 two level fusions (L4-S1).
      Odom Criteria 3, 6, and 12 months postoperatively revealed continued improvement
      for all patients. SF-36 outcomes, however, revealed deterioration on 2 Health
      Scales (Role Physical, Role Emotional) 3 and 6 months post-operatively, and
      minimal to marked improvement on 6 Health Scales (PF, V, PF, V, SF, BP). Twelve
      months postoperatively improvement occurred on all 8 Health Scales, exceeding pre
      operative baselines; minimal (RP, GH), mild (MH), moderate (PF, BP, V, SF), and
      marked improvement (RE). Although Vitoss/B-TCP and laminar autograft resulted in
      pseudarthrosis for 1 of 27 single level and 2 of 13 two level posterolateral
      instrumented lumbar fusions, only 1 of the latter patients required a secondary
      fusion.

PMID- 16891979
TI  - Radiological grading of cervical destructive spondyloarthropathy in long-term
      hemodialysis patients.
AB  - On the basis of the radiological findings of dialysis patients, we made a
      radiological grading and analyzed the progression of destructive
      spondyloarthropathy (DSA) using this grading system. In this system, the
      radiological features of the vertebral endplates and intervertebral disc spaces
      were divided into 4 grades (grade 0 to grade III). Grades II and III were defined
      as DSA. In this study, out of the 787 dialysis patients (447 men and 340 women,
      mean age: 60.0 years) examined, 133 patients (16.9%) were diagnosed with DSA.
      During 7 years follow-up, 108 dialysis patients were examined to investigate the
      clinical characteristics of DSA. Fifteen of 90 non-DSA cases progressed to DSA.
      Six of 18 DSA cases showed grade progression. The duration required for
      progression of each grade was analyzed. A new classification of DSA, namely,
      degenerative DSA and classical DSA, was applied in this study. The degenerative
      DSA showed faster grade progression than the classical DSA. Therefore, great
      attention should be paid in the radiological follow-up of elderly patients with
      grade I who start dialysis at an old age.

PMID- 16891981
TI  - A biomechanical study of 3 different types of sublaminar wire used for constructs
      in the thoracic spine.
AB  - A biomechanical study was carried out on 3 different types of sublaminar wire
      used in constructs to secure the thoracic spine: stainless steel monofilament
      wire (steel wire), titanium cable (cable), and ultra-high molecular weight
      polyethylene tape (tape). Two experiments were carried out. Experiment 1: Thirty
      one fresh human thoracic vertebrae classified as osteoporotic (bone mineral
      density of <0.8 g/cm2) were used. The steel wire, cable, or tape was placed
      sublaminarly and a tensile force was applied until the steel wire, cable, or tape
      cut 5 mm through the lamina, and the force at this point was noted. Experiment 2:
      Seven fresh human thoracic spines (T7-T10) were biomechanically tested as
      follows: axial compression (250 N), flexion (7.5 Nm), extension (7.5 Nm), left
      lateral bending (7.5 Nm), right lateral bending (7.5 Nm), left axial torsion (10
      Nm), and right axial torsion (10 Nm). This sequence was applied to the intact
      spine. The spine was then de-stabilized and then restabilized using one or other
      of the 3 different types of sublaminar wires. The biomechanical testing was then
      repeated on the restabilized spine and stiffness curves were generated. In the
      laminar cut-through test, the cut-through force for tape was higher than that for
      either steel wire or cable. In the biomechanical stiffness testing, there was no
      significant difference between the 3 different sublaminar wiring constructs in
      any of the loading modes tested. The results of both experiments suggest that
      tape is as good, if not better, than steel wire or cable as a sublaminar wiring
      construct material.

PMID- 16891980
TI  - Accuracy of pedicle screw placement for upper and middle thoracic pathologies
      without coronal plane spinal deformity using conventional methods.
AB  - There is a growing interest in the implantation of pedicle screws into the middle
      and upper thoracic spine. However, usage of the technique is still under debate
      for these levels because the pedicles in these regions are small and exhibit a
      high degree of inter- and intraspecimen variability. Twenty-four consecutive
      patients treated for upper and middle thoracic pathologies by pedicle screw
      instrumentation under biplanar or uniplanar fluoroscopy were evaluated
      retrospectively. The rate of screw misplacement on postoperative computerized
      tomography and complications caused by misplaced screws were determined. In 24
      cases, a total of 113 upper-middle thoracic pedicle screws were inserted. Fifty
      one of them were inserted between T2 and T5 with guidance of biplanar
      fluoroscopy, and 62 were inserted between T6 and T8 with uniplanar fluoroscopy.
      The rate of misplacement was 20.3% for 113 screws (27.4% for T2 to T5 screws, and
      14.5% for 62 T6 to T8 screws). Four screws were incorrectly inserted which could
      have clinical significance (3.5%), and 1 of them required revision. The
      difference between the upper and middle thoracic screws was not statistically
      significant (P=0.089). Screw insertion with laminectomy did not cause significant
      difference in both upper and middle thoracic regions. Only 2 complications were
      seen because of screw insertion. Pedicle screw insertion with guidance of
      fluoroscopy may be a reliable and safe method for upper and middle thoracic
      pathologies.

PMID- 16891982
TI  - Far lateral extraforaminal facet cyst causing L5 radiculopathy.
AB  - Most synovial cysts of the lumbar spine appear as intraspinal extradural masses
      adjacent to the facet joint. Almost all symptomatic synovial cysts are located
      within the spinal canal and or the neural foramen. To our knowledge, only 6 cases
      of symptomatic extraspinal synovial cysts have been described in the literature.
      The authors report a case of lumbar radiculopathy caused by a synovial cyst
      located in the far lateral extraforaminal area. The patient underwent
      decompression of the L5 nerve root with recapping right isthmectomy and
      facetectomy. Postoperative recovery was uneventful, and the patient was totally
      pain free with no motor deficit. Symptomatic synovial cysts are uncommon lesions
      that are associated with degenerative disease of the spine. Juxtafacet cysts
      should be considered in the differential diagnosis of space-occupying lesions at
      the extraforaminal areas. Recapping isthmectomy and facetectomy are useful
      procedures for a synovial cyst located in the far lateral extraforaminal area.

PMID- 16891983
TI  - Vertebral hemangioma symptomatic during pregnancy treated by posterior
      decompression, intraoperative vertebroplasty, and segmental fixation.
AB  - Hemangioma is one of the most common benign tumors of the spine, and it remains
      silent in the vast majority of the subjects afflicted. Pregnancy is a known risk
      factor for symptomatic conversion of the previously dormant vertebral
      hemangiomas. However, the occurrence is rare with only 24 cases reported in the
      literature. The authors present a case of vertebral hemangioma symptomatic during
      the third trimester of pregnancy. The patient, a 20-year-old woman in her 33rd
      week of pregnancy, initially presented with acute back and bilateral leg pain,
      and developed the cauda equina syndrome within a week of its onset. Imaging
      studies revealed an L2 vertebral hemangioma, and the thecal sac was severely
      compressed by the epidural portion of the tumor. Emergency decompression and
      reconstruction surgery was undertaken 3 days after an uneventful cesarean
      section. The combined surgical management, consisting of laminectomy,
      intraoperative vertebroplasty, and segmental fixation, afforded adequate
      decompression, instant mechanical stability of the spine, and prompt pain
      elimination. The long-term efficacy of this combined treatment is unclear and
      needs to be followed cautiously.

PMID- 16891984
TI  - Traumatic anterior lumbosacral dislocation caused by hyperextension mechanism in
      preexisting L5 spondylolysis: a case report and a review of literature.
AB  - Of many reports referring to injury mechanism in anterior lumbosacral
      dislocation, there were none concerning hyperextension mechanism. We report a
      case of a 46-year-old man with preexisting L5 spondylolysis sustaining traumatic
      complete anterior lumbosacral dislocation. The operative findings, together with
      the radiologic findings, strongly suggested that the dislocation occurred by
      hyperextension mechanism. Open reduction was done by applying force of
      distraction with flexion using a rod and screw system, followed by the internal
      fixation from the L3 to S1 vertebrae and the postero-superior iliac spine. The
      lumbosacral dislocation was reduced to 77%. At the follow-up at 5 years after
      surgery, bony union was obtained and the patient could move with a wheelchair
      although the neurologic deficit in lower extremities observed preoperatively did
      not recover. Preexisting L5 spondylolysis was considered to increase the
      potential for anterior lumbosacral dislocation by additional force of compression
      with hyperextension. Posterior instrumentation using a rod and screw system was
      considered a useful method for reduction, decompression, stabilization, and
      fusion.

PMID- 16891985
TI  - Intraoperative electromyography for pedicle screws: technique is the key!

PMID- 16891986
TI  - The nutrition diagnosis: how it fits in the nutrition care process.

PMID- 16891987
TI  - The relationship between adiponectin levels and metabolic status in centenarian,
      early elderly, young and obese women.
AB  - OBJECTIVES: Adipose tissue secretes proteins which regulate energy metabolism and
      insulin sensitivity. Adiponectin possesses anti-diabetic, anti-atherogenic and
      insulin-sensitizing properties. To assess the prognostic factors in prolonged
      survival and the potential protective role of adiponectin in aging, we examined
      the release of adiponectin in relation to the metabolic status of centenarians,
      compared with young, early elderly and obese subjects. MATERIAL AND METHODS: The
      study was carried out on 122 women: 22 centenarians aged 100-102 yrs, 45 younger
      women aged 20-43 yrs, 19 early elderly women aged 64-67 yrs, and 36 obese women
      aged 26-54 yrs. Anthropometric data, clinical features and blood samples were
      obtained. Plasma adiponectin and insulin concentrations were measured by RIA
      methods. Fasting plasma glucose levels, lipid profile and creatinine
      concentrations were determined using routine laboratory procedures. RESULTS: In
      centenarians we found that adiponectin concentrations were significantly
      increased, compared with young, early elderly and obese women. Insulin
      concentrations were lower than those in young and obese subjects. HOMA-IR was
      significantly lower than in obese women. Positive correlations were found between
      adiponectin and HDL, and negative correlations between adiponectin and HOMA-IR,
      total cholesterol, LDL, triglycerides, blood pressure and BMI. CONCLUSION: Our
      results indicate that adiponectin may play a protective role that contributes to
      longevity.

PMID- 16891988
TI  - The immature endothelial cell in new vessel formation following surgical injury
      in rat brain.
AB  - OBJECTIVES: We investigated neovasculatization in the cerebral cortex of the
      adult rat after surgical brain injury by ultrastructural, immunocytochemical and
      immunochemical means. Previously we described endothelial-like cell that
      participates in new vessel formation on plasma proteins that served as a
      provisional matrix in the region immediately adjacent to the traumatic injury. In
      the present study we describe new vessel formation in the multistep process with
      the alterations in endothelial-like cell immunophenotype. METHOD: The
      observations were conducted from 2 to 7 days after induction of cortical trauma.
      Traumatic injury was induced in the frontotemporal region of cerebral cortex.
      RESULTS: We show that endothelial-like cell could not successfully terminate its
      development without the presence of pericyte and astrocyte. New formed blood
      vessels were accompanied by fibroblast and lipofibroblast cells differentiated
      probably from common progenitor. MAIN FINDINGS: Our result suggests that
      endothelial-like cell is committed endothelial cell between progenitor
      endothelial cell and terminally differentiated endothelium stage. Therefore, we
      propose that our of endothelial stem cells present in blood at different stages
      of morphogenetic differentiation and specifically arrested in "check points" of
      development trauma mobilize the group of the most differentiated progenitors.
      These may contribute to new vessel formation. CONCLUSION: Our model should be
      useful for the characterization of endothelial commitment and endothelial cell
      differentiation after brain injury.

PMID- 16891989
TI  - The occurrence of genital types of human papillomavirus in normal pregnancy and
      in pregnant renal transplant recipients.
AB  - OBJECTIVE: The aim of this study was to evaluate: 1) The prevalence of human
      papillomavirus (types 6 and 11 carrying a low risk of neoplasia, and type 16
      implicated as cause of cervical neoplasia and cancer) in normal pregnant women
      and pregnant renal transplant recipients. 2) The correlation between maternal HPV
      infection and HPV presence in the cord blood and the oral cavity of the neonate.
      Evaluation of a likely, additional route of HPV transmission to the fetus, apart
      from the infected birth canal during vaginal delivery. The correlation between
      the mode of delivery in HPV-infected patients and the presence of HPV in their
      offspring. DESIGN: Thirty-nine pregnant patients were included in the study. The
      study group consisted of nine pregnant renal transplant recipients. The control
      group consisted of 30 patients with normal pregnancy. The DNA of HPV types 6, 11
      and 16 was studied in the discharge from the cervical canal, the maternal venous
      blood, the cord blood and the buccal smear obtained from the neonates. SETTING: A
      university teaching hospital delivering approximately 2000 women annually.
      RESULTS: Human papillomavirus (HPV) was found in 10 (26%) of 39 subjects. HPV
      types 6 and 11 was found in 7 (18%) of 39 subjects while HPV type 16 was present
      in 5 (13%) of the subjects. The co-occurrence of HPV types 6, 11 and 16 was
      detected in 2 patients from the control group. Transmission of HPV was
      established in 70% of study patients and their offspring. CONCLUSIONS: 1) The HPV
      was found with 26% pregnant women. 2) The occurrence of HPV infections with
      pregnant renal transplant recipients in comparison with normal pregnancy was on
      similar level. High percentage of HPV transmission from mother to neonate was
      obtained. 3) The cesarean section probably doesn't protect from HPV infection. 4)
      There's a suggestion, the HPV infection of fetus may occur in utero.

PMID- 16891990
TI  - The evaluation of uterine cavity with saline infusion sonohysterography and
      hysteroscopy in infertile patients.
AB  - OBJECTIVES: The preliminary study was performed to evaluate the diagnostic
      accuracy of saline infusion sonohysterography (SIS) in the detection of
      intrauterine pathologies in infertile women The SIS findings were compared to the
      results of two widely used procedures: transvaginal sonography (TVS) and
      hysteroscopy (HS). MATERIAL AND METHODS: 68 infertile women, aged 27-42 were
      enrolled in the study. TVS, SIS and diagnostic HS were consecutively performed in
      every patient. The results of each method were compared. Sensitivity,
      specificity, positive predictive value and negative predictive values for TVS and
      SIS were obtained. RESULTS: Intrauterine pathologies were diagnosed in 25% of
      patients. TVS detected 6 (37.5%) and SIS revealed 11 (87.5%) of 13 intrauterine
      pathologies finally visualized at diagnostic hysteroscopy. TVS failed to
      visualize three submucous myomas, one endometrial polyp and two cases of septate
      uteri. All three cases of intrauterine synechiae were not detected with this
      method One submucous myoma and one endometrial polyp were not identified with
      SIS. The study group was, however, too limited to show statistically significant
      differences in diagnostic accuracy among TVS, SIS and HS. CONCLUSIONS: Saline
      infusion sonohysterography is simple, sensitive and inexpensive diagnostic
      method. The procedure is not time-consuming, causes minimal discomfort to the
      patient and may be performed without anesthesia in office settings. The method
      may be recommended for the diagnosis of intrauterine pathologies in infertile
      women.

PMID- 16891991
TI  - The analgesic effect of pamidronate is not caused by the elevation of beta
      endorphin level in Paget's disease--a controlled pilot study.
AB  - INTRODUCTION: Although an analgesic effect is an essential component of the mode
      of action of bisphosphonates, its physiological mechanisms are still unclear.
      Beta-endorphin release plays an important role in the analgesic effect of both
      calcitonin and raloxifene. As patients with Paget's disease receive large doses
      of bisphosphonates within relatively short time periods, we examined whether
      repeated pamidronate infusion therapy would cause measurable change in beta
      endorphin levels MATERIALS & METHODS: Visual analog scale (VAS) scores of pain
      intensity, beta-endorphin levels, and alkaline phosphatase activity of 11
      patients with Paget's disease (7 with the mono- and 4 with the polyostotic form)
      were determined at baseline, as well as after 3 and 6 infusions (on Days 6 and 12
      of treatment, respectively). Eleven untreated patients with Paget's disease (7
      with the mono- and 4 with the polyostotic form) served as controls. RESULTS: It
      was established that in the course of pamidronate infusion therapy BE levels
      remained constant, whereas the values in serum alkaline phosphatase and pain
      intensity scores were significantly reduced. CONCLUSIONS: Although high-dose
      pamidronate therapy does mitigate pain substantially (as demonstrated by the
      reduction of VAS scores), its analgesic action is probably unrelated to the
      enhancement of beta-endorphin release.

PMID- 16891992
TI  - Testosterone levels and discounting delayed monetary gains and losses in male
      humans.
AB  - OBJECTIVES: Although impulsivity has been associated with androgens (e.g.,
      testosterone), little is known regarding the relationship between testosterone
      levels and impulsivity in intertemporal choice (delay discounting). This study
      was aimed to examine the relationship between delay discounting of gains and
      losses and testosterone levels, which is of interest in neuroendocrinology and
      neuroeconomics. METHODS: We assessed degrees to which delayed monetary gains and
      losses were discounted (hyperbolic discounting rate) in healty male students
      (age: 22.4+/-2.67). Participants' salivary testosterone levels were also assessed
      by utilizing liquid chromatography/mass spectroscopy (LC/MS) method. RESULTS: Non
      linear curve fitting analysis showed an inverted-U relationship between delay
      discounting of gains and salivary testosterone levels; while no relationship
      between salivary testosterone levels and delay discounting of losses was
      observed. CONCLUSIONS: The results indicate that (i) testosterone may enhance
      delay discounting rate of gains in non-impulsive subjects, (ii) testosterone may
      have an opposite (reducing) effect on delay discounting rate of gains in
      impulsive subjects, and (iii) testosterone is unrelated to subject's sensitivity
      to future bad outcomes. Implications for evaluating the effects of testosterone
      treatment and anti-androgenic therapy on impulsive behavior often observed in
      psychiatrics (e.g., pathological gambling, credit card debt, substance misuse,
      and needle-sharing) are discussed.

PMID- 16891993
TI  - Serum leptin levels in children with cerebral palsy: relationship with growth and
      nutritional status.
AB  - AIM: Children with Cerebral Palsy (CP) are generally undernourished and growth
      retarded than normal children. The reasons of malnutrition are not only due to
      poor nutritional status but also nonnutritional factors including negative
      neurotrophic effects and indirect factor such as immobility, endocrinological
      abnormalities or spasticity that energy requirements might be contributing
      factors. Several studies indicated that leptin which is produced by adipocytes,
      might regulate energy intake and expenditure. The aim of this study is to
      determine serum leptin levels in children with CP and to investigate the
      relationship between nutritional status and anthropometric measurements. METHODS:
      Forty children with CP and 18 healthy controls were included in this study. The
      weight, height, body mass index (BMI), upper arm length (UAL) and triceps
      skinfold thickness (TST) was measured in all children. Serum leptin, growth
      hormone, C-peptide and cortisol levels were studied. Based on TST measurement CP
      patients were divided as DSF group (decreased subcutaneous fat) and non-DSF group
      (nondecreased subcutaneous fat). RESULTS: UAL were shorter and TST measurements
      were thinner than control group (p<0.05, p<0.01). Group DSF had lower leptin
      concentrations compared to Group non-DSF and controls (p<0.001, p<0.001). On the
      other hand non DSF group had higher leptin levels than controls (p<0.05). There
      was a positive and significant correlation between leptin and anthropometric
      measurements, especially TST in children with CP. Serum leptin levels were also
      lower in non-ambulatory children than ambulatory children with CP (p<0.05).
      CONCLUSION: This study has shown that triceps skinfold thickness is better index
      for the evaluation of nutritional status in children with CP. Serum leptin levels
      were lower in CP, especially in DSF group. The possible explanation of this
      finding may not only related with malnutrition, but also immobility related other
      factors such as bone metabolism and spasticity. We concluded that leptin which
      regulates energy intake might have a role of nutritional disorders in cerebral
      palsy. To better understand this relationship further studies are needed.

PMID- 16891994
TI  - Right occipital cortex suppresses male rat testosterone secretion by a pituitary
      independent mechanism.
AB  - OBJECTIVES: In addition to being regulated by the hypothalamo-hypophyseal system,
      testosterone (T) secretion is influenced by a number of less understood
      mechanisms. The aim of the present study was to examine whether defined areas of
      the right cerebral cortex could modulate T production. METHODS: In adult male
      Wistar rats right frontal or occipital decortication, anterior or posterior
      callosotomy and corresponding sham-operations were performed. After 7-day
      survival time, T secretion in vitro, serum T and LH concentrations were measured
      by RIA. RESULTS: Right occipital decortication and posterior callosotomy resulted
      in an increase in T secretion in vitro when compared to the corresponding sham
      operated controls. In contrast, right frontal decortication or anterior
      callosotomy did not interfere with steroidogenesis. Serum LH concentration was
      not altered by any interventions. CONCLUSION: The right occipital but not the
      right frontal cortex is involved in the control of T secretion. The caudal part
      of the corpus callosum accommodating the fibers originating from the occipital
      cortex might have a similar function. The fact that LH remained unchanged in all
      experimental groups suggests that the right occipital cortex and the caudal part
      of the corpus callosum influence testicular steroidogenesis by a pituitary
      independent mechanism.

PMID- 16891995
TI  - Relation of low-grade inflammation and endothelial activation to blood pressure
      in obese children and adolescents.
AB  - OBJECTIVE: To determine the role of low-grade, systemic inflammation and
      endothelial activation in the modulation of blood pressure (BP) independently of
      other traditional risk factors in obese children and adolescents. DESIGN: We
      surveyed 281 obese subjects, aged 6-18 years to investigate the relationship of
      serum inflammation and endothelial activation markers and blood pressure.
      MEASUREMENTS: Clinical variables, indices of obesity, ambulatory 24-h blood
      pressure and serum concentrations of C-reactive protein (CRP), interleukin-6 (IL
      6), interleukin-1 beta (IL-1 beta), intercellular cell adhesion molecule-1 (ICAM
      1), vascular cell adhesion molecule-1 (VCAM-1), glucose and insulin. HOMA IR was
      used as a marker of insulin resistance (IR). RESULTS: CRP, IL-6, IL-1 beta, and
      ICAM-1 correlated significantly with mean 24-h systolic BP, whereas CRP and IL-6
      was positively correlated with mean 24-h diastolic BP. Multiple regression
      analysis showed that serum IL-6 (P < .001) concentration, HOMA IR (P < .01), and
      waist to hip ratio (P < .05) were the significant determinants of systolic BP,
      whereas CRP (P < .05) level was the only predictor of diastolic BP. There were no
      significant associations of cell adhesion molecules with BP. CONCLUSIONS: These
      results indicate that low-grade inflammation may play a role in the modulation of
      arterial BP relatively early in life.

PMID- 16891997
TI  - Oxidative status--age- and circadian variations?--a study in leukocytes/plasma.
AB  - OBJECTIVES: In the present paper the circadian variation and age differences in
      human leukocyte reactive oxygen species (ROS) levels and plasma total antioxidant
      status were studied. Different ROS levels could influence disease during ageing
      and at different times of the day/night. METHODS: Unstimulated and stimulated (12
      O-tetradecanoyl-phorbol-13-acetate (TPA) blood samples were analysed by flow
      cytometry using dihydroethidium (DHE) and dihydrorhodamine 123 (DHR) as probes.
      60 healthy individuals were divided into five equal groups ((I) 1-2 days post
      partum, (II) 20 +/- 2 years, (III) 40 +/- 2 years, (IV) 60 +/- 2 years and (V) 80
      +/- 2 years) and 6 healthy volunteers were followed with blood samples at 3 hour
      intervals for 24 hours. RESULTS: We observed a significant peak of ROS levels in
      both monocytes and granulocytes at 6 pm and 3 am using DHE as probe. DHR showed
      in principle the same pattern. The monocytes (unstimulated and stimulated) and
      unstimulated granulocytes of the newborn group showed higher ROS values than all
      the other groups, whereas the groups of adults did not differ from each other.
      The plasma total antioxidant status was significantly higher in the newborn group
      and showed no circadian variation. CONCLUSIONS: The present data show that there
      is a circadian variation of ROS production in leukocytes that might possibly
      influence the occurrence of cardiovascular incidents like myocardial infarction.
      No increase in ROS production was found in healthy elderly compared to younger
      individuals. The increased ROS levels and antioxidant status of newborns might
      influence neonate immunity and play a part in cell signalling and development.

PMID- 16891996
TI  - Polyunsaturated fatty acids: do they have a role in the pathophysiology of
      autism?
AB  - OBJECTIVES: There is now some evidence that alterations in fatty acids may play a
      role in the pathophysiology of autism. The aim of the present study was to
      examine whether autism is accompanied by abnormalities in the composition of the
      polyunsaturated fatty acids (PUFAs) in plasma phospholipids. METHODS: The plasma
      phospholipid omega-3 (3) and omega-6 (6) PUFA fractions and the 3/6 ratio were
      measured in 16 high-functioning male youngsters with autism (age 12-18) and 22
      healthy volunteers. Group mean differences were assessed by means of analysis of
      variance (ANOVA). RESULTS: In autism there was a significant increase in the
      fraction of C22:6-3 (docosahexaenoic acid, DHA) and an increase in the total 3/6
      ratio. DISCUSSION: The results of this study suggest that an increase of the
      plasma phospholipid 3 PUFAs, in particular DHA, and of the total 3/6 ratio may
      take part in the pathophysiology of autism. One hypothesis is that an increase of
      3 PUFAs may cause alterations in the serotonergic turnover and the immune
      response system, both known to be associated with autism. Caution must be
      exercised against highly concentrated 3 PUFAs supplementation.

PMID- 16891999
TI  - Mercury toxicity presenting as chronic fatigue, memory impairment and depression:
      diagnosis, treatment, susceptibility, and outcomes in a New Zealand general
      practice setting (1994-2006).
AB  - In a group of 465 patients diagnosed as having chronic mercury toxicity (CMT),
      32.3% had severe fatigue, 88.8% had memory loss, and 27.5% had depression. A
      significant correlation was found between CMT and the Apo-lipoprotein E4 genotype
      (p=0.001). An investigation into an additional 864 consecutively seen general
      practice patients, resulted in 30.3% having evidence consistent with CMT, and
      once again a significant correlation was found with the APO-E4 genotype
      (p=0.001). Removal of amalgam mercury fillings when combined with appropriate
      treatment resulted in a significant symptom reduction (p<0.001) to levels
      reported by healthy subjects.

PMID- 16891998
TI  - Moclobemide and cognitive behavioral therapy in the treatment of social phobia. A
      six-month controlled study and 24 months follow up.
AB  - The aim of the study was to assess the 6-months treatment efficacy and 24-month
      follow up of three different therapeutic programs (A. moclobemide and supportive
      guidance, B. group cognitive-behavioral therapy and pill placebo, and C.
      combination of moclobemide and group cognitive-behavioral therapy) in patients
      with a generalized form of social phobia. Eighty one patients (38 males and 43
      females) were randomly assigned to three different therapeutic programs. Patients
      were regularly assessed on a monthly basis by an independent rater on the LSAS
      (Liebowitz Social Anxiety scale), CGI (Clinical Global Impression) for severity
      and change and BAI (Beck Anxiety Inventory). Altogether, sixty-six patients
      completed the six month treatment period and 15 patients dropped out. All
      therapeutic groups showed significant improvement. A combination of CBT and
      pharmacotherapy yielded the most rapid effect. Moclobemide was superior for the
      reduction of the subjective general anxiety (BAI) during the first 3 months of
      treatment, but its influence on avoidant behavior (LSAS avoidance subscale) was
      less pronounced. Conversely, CBT was the best choice for reduction of avoidant
      behavior while a reduction of subjective general anxiety appeared later than in
      moclobemide. After 6 months of treatment there were best results reached in
      groups treated with CBT and there was no advantage of the combined treatment. The
      relapse rate during the 24-month follow up was significantly lower in the group
      treated with CBT in comparison with the group A. formerly treated with
      moclobemide alone.

PMID- 16892001
TI  - LH release by Cu and Ni salts and metal-GnRH complexes, in vitro.
AB  - The present studies were undertaken to examine the effect of copper and nickel
      salts and their complexes with GnRH on LH release from the pig anterior pituitary
      cells in vitro. The potency of Cu-GnRH and Ni-GnRH binding to GnRH receptors with
      iodinated GnRH as a radioactive tracer was also verified. The incubation of pig
      pituitary cells with Cu and Ni acetate salts showed no effect of the studied ions
      on LH release at any concentration used. However, nickel salt at a lower dose
      (10(-10) and 10(-9) M) tended to decrease LH output. By contrast, the native GnRH
      as well as its metal complexes significantly stimulated LH release after three
      hours of treatment and Cu-GnRH was found to be the most effective. The results
      showed that Cu and Ni complexes with GnRH but not their acetate salts are
      effective in LH release from pig pituitary cells collected from adult female
      pigs.

PMID- 16892000
TI  - Low-grade systemic inflammation and the risk of type 2 diabetes in obese children
      and adolescents.
AB  - BACKGROUND: There is growing evidence that low-grade systemic inflammation is
      closely involved in the pathogenesis of type 2 diabetes. OBJECTIVE: The aim of
      this study was to investigate the relationship between serum inflammatory markers
      and selected parameters known as risk factors of type 2 diabetes in obese
      children and adolescents. SUBJECTS AND METHODS: Fasting levels of C-reactive
      protein (CRP), fibrinogen (FB) interleukin-6 (IL-6), interleukin 1-beta (IL
      1beta), glucose, insulin, total, HDL and LDL cholesterol, triglycerides, white
      blood cell count (WBC) and fasting glucose to insulin ratio (FGIR) were measured
      in 281 obese children and adolescents. Pearson's correlation was used for
      assessing the relationship between inflammatory markers and selected clinical
      parameters. RESULTS: Inflammatory markers correlated significantly with insulin
      resistance indices, HbA1c, lipid profile, hypertension, positive family history
      of type 2 diabetes, low physical fitness, and mixed high-fat and high
      carbohydrate diet. CONCLUSIONS: Serum inflammatory markers were significantly
      correlated with most factors implicated in the development of type 2 diabetes.
      These data provide additional support for previously reported in adults
      relationship between subclinical inflammation and the risk of type 2 diabetes.

PMID- 16892002
TI  - Key aspects of melatonin physiology: thirty years of research.
AB  - Numerous studies of melatonin, by now widely acknowledged as a circadian rhythm
      affecting neurohormone, also describe its anti-oxidant, anti-cytotoxic or immune
      modulating activity. While emphasizing the multifunctional aspect of melatonin
      action, this review presents the results of our thirty years of research, which
      point to the following conclusions: melatonin is capable of promoting platelet
      production by megakaryocytes, of acting on the latter's ion channels by way of
      the outward currents, and of performing a physiological anti-aggregation function
      thus lengthening platelet life span. Melatonin can be transported everywhere by
      platelets and, thanks to its lipophilicity, can cross cellular membranes easily,
      thus regulating blood-tissue exchanges and ensuring an improved haematic crisis.
      It interacts with endothelial cells by regulating their release of both relaxing
      factor and contracting-factor, and with platelets by affecting their discharge of
      dense-body components. Finally, platelets could behave as mobile and itinerant
      serotonergic and/or melatonergic elements, a function comparable to the release
      of neurotransmitters by neurons of the central nervous system. This dynamism in
      melatonin physiology could prove to be a key in approaching tumour
      aetiopathogenesis.

PMID- 16892003
TI  - Immunoreactivity of ubiquitin in human prostate gland.
AB  - BACKGROUND: Ubiquitin is a low molecular weight protein which has been detected
      in a variety of normal and cancerous tissues. It is involved in many regulatory
      processes including protein proteolysis. It has been implicated in tumor
      pathogenesis. The role of ubiquitin in human prostate gland is investigated in
      this study. METHODS: In this study, we utilized immunohistochemistry technique to
      localize ubiquitin in human prostate gland and correlate it with different
      pathological conditions of the prostate. RESULTS: Ubiquitin was localized in
      normal, benign prostatic hyperplasia (BPH) and prostatic adenocarcinoma with
      variations in the distribution and intensity. In BPH, ubiquitin immunoreactivity
      was localized mainly in the nuclei while in the adenocarcinoma was localized
      mainly in the cytoplasm. CONCLUSION: The presence of ubiquitin mainly in the
      nuclei and in the cytoplasm of BPH and prostatic adenocarcinoma, respectively,
      may suggest a role of ubiquitin in the development of the above mentioned
      conditions. Ubiquitin could be used as a potential marker for the diagnosis and
      prognosis of pathological conditions of the prostate.

PMID- 16892004
TI  - Hypercalcemia in glioblastoma multiforme.
AB  - Hypercalcemia is commonly associated with cancer, occurring in around 10-20% of
      cancer patients. Hypercalcemia is usually related to solid and non-solid
      malignancies specifically breast cancer, lung cancer and multiple myeloma.
      Hypercalcemia has been reported to occur in association with astrocytomas, and
      uncommonly in gliomas. We report a case of a previously healthy man presenting
      with glioblastoma multiforme . He was found to have persistently elevated serum
      calcium and calcitriol with normal parathyroid function. This is the first
      reported case of hypercalcemia associated with glioblastoma multiforme.

PMID- 16892005
TI  - Gonadotrophin levels and morphological testicular features in rats after
      different doses of the phytoestrogen coumestrol.
AB  - INTRODUCTION: Phytoestrogens are a wide variety of chemical compounds, mainly
      isoflavonoids, from a vegetable source. Their name makes reference to their
      ability to induce estrogenic responses in mammals. Coumestrol is a phytoestrogen
      that can be found in high concentrations in the dietary elements of cattle. Some
      endocrine alterations have been reported for cows and ewes after ingestion of
      vegetables with high concentrations of coumestrol. However, these studies have
      been made mainly in females. OBJECTIVE: To analyze some features of the masculine
      endocrine response in rats after several doses of the phytoestrogen coumestrol.
      DESIGN: Adult male rats were injected with several doses of coumestrol. Plasma
      gonadotrophins (LH/FSH) and testosterone levels were assessed. In addition,
      morphology of the testicles was analyzed. SETTING: Experiments were done in the
      facilities of the neurosciences area at the University. RESULTS: No significant
      changes were observed in gonadotrophin levels after the administration of
      coumestrol. Testosterone levels showed a significant decrease with the higher
      doses. Morphological analysis showed an inhibitory effect on spermatogenesis
      expressed mainly in the right testicle. Testicular volume decreased and the
      tubular area increased significantly after coumestrol treatment. CONCLUSIONS:
      These results suggest that the endocrine effect of coumestrol is mainly expressed
      in peripheral targets in male rats. In addition, the possible mediation of
      estrogen beta receptors is discussed.

PMID- 16892006
TI  - Emil Starkenstein--one of the most important personalities of European
      continental pharmacology in the period between the two world wars.
AB  - Emil Starkenstein (1884-1942), professor of pharmacology at the German Medical
      Faculty of Charles University in Prague, was not only an experimental
      pharmacologist, but also the pioneer of clinical pharmacology. During the World
      War I (1914-1918) he took advantage of his knowledge of experimental pharmacology
      for the new approaches to the treatment of bacillary dysentery, cholera and of
      epidemic typhus fever. In 1918 he published the article "Clinical Pharmacology-
      Theory and Praxis at the Patient's Bedside", in which he defined the main task of
      clinical pharmacology as the implementation and verification of experimental
      pharmacology achievements in clinical therapy. During the period 1921-1933, his
      scientific interests involved namely analgesic combinations, seasickness therapy
      and pharmacology of iron. He published more than 240 scientific articles and
      three textbooks. Emil Starkenstein died on November 6, 1942 as a victim of
      Holocaust. Starkenstein s collection of more than 20,000 reprints of scientific
      studies, which has been deposited recently in the Archives of Charles University
      in Prague is very valuable.

PMID- 16892007
TI  - Effect of six weeks aerobic training upon blood trace metals levels.
AB  - This study was carried out to investigate the effects of 6-week aerobic exercise
      program upon blood Zn and Cu levels. There were 12 male university students with
      an average age of 21.67+/-0.89 years and no regular training habits participated
      in the study. The participants were subjected three days a week 1 hour a day
      continuous running program on treadmill with an intensity of 60-70% for a period
      of six weeks. They were fed with zinc and copper free diet throughout the study
      and it was made sure that they were not using copper or zinc containing vitamin
      tablets. The difference between the pre and post study period were found to be
      statistically significant as regards to both resting and maximal loading
      conditions (p<0.01). The pre and post training maxVO2 values were also found to
      be positively correlated with the copper and zinc levels in blood. Both the
      copper and zinc blood levels were found decreased after the training period
      p<0.05.

PMID- 16892008
TI  - Dexamethasone suppression test in first-episode schizophrenia.
AB  - OBJECTIVES: Higher rates of dexamethasone test (DST) nonsuppression in
      schizophrenia have been attributed to depressive symptoms, suicidality and
      negative symptoms. No study concerning first-episode schizophrenia has yet been
      published. DESIGN: In patients hospitalised for the first time with first-episode
      schizophrenia the DST has been performed before, at the end of the acute
      treatment and after one year. At the same time the clinical evaluation with PANSS
      was performed. A cortisol value >5 microgram/dl in either of the
      postdexamethasone samples indicated nonsuppression of cortisol. RESULTS: A total
      of 56 males were included. 18% of pts were DST nonsuppressors at medication-free
      baseline, 5% and 16% after acute treatment and after one year respectively. After
      1 year 42/56 of patients fulfilled the criteria of remission. The rate of
      nonsuppression was 21.4%, 5% and 16.4% in remitters and 7%, 7% and 14.3% in
      nonremitters. Significant differences in the whole group were found between
      postdexamethasone cortisolemia at discharge on the one hand and on admission and
      at the one-year follow-up on the other. Significant correlations were observed
      between postdexamethasone cortisolemia and negative symptoms at the end of acute
      treatment. MAIN FINDINGS: In first-episode schizophrenia the short-term treatment
      led to a decrease in cortisolemia and rates of nonsuppression and an increase at
      a one-year follow-up. CONCLUSIONS: Rates of DST nonsuppression in schizophrenia
      including first-episode schizophrenia are influenced by the stage of illness and
      medication status. The impairment of feedback regulation of cortisol secretion
      may be related to different biopathogenetic mechanisms depending on the phase of
      the illness.

PMID- 16892009
TI  - Soft and hard tissue response to zirconium dioxide dental implants--a clinical
      study in man.
AB  - Titanium dental implants have been used successfully in implantology for more
      than 40 years. Recent research, however, suggests that titanium might have more
      side effects than previously believed. Zirconia ceramics have been employed in
      orthopaedic surgery for approximately 30 years and were recently introduced into
      dentistry as a metal replacement for crown and bridge work as well as implant
      abutments. Zirconium dioxide has been shown in both in vitro and in vivo studies
      to have desirable osseointegrative properties. This clinical study shows that
      dental implants made from zirconia are a feasible alternative to titanium dental
      implants. In addition to excellent cosmetic results, zirconia implants allow a
      degree of osseointegration and soft tissue response that is superior to titanium
      dental implants.

PMID- 16892010
TI  - In vivo effects of dental casting alloys.
AB  - OBJECTIVE: Corrosion products of different metallic alloys used in prosthetic
      dentistry often cause the development of a bluish-grey pigmentation of gingiva
      and oral mucosa. The aim of this study was to determine the content of metals in
      metallic pigmentations and evaluate the immune response to metals found in the
      oral cavity. MATERIAL AND METHODS: The local tissue reactions were investigated
      clinically by electron microscopy and by energy dispersive x-ray microanalysis.
      An extensive anamnesis of the patients was recorded as well as earlier contacts
      with health care institutions. The immunological response to metallic components
      of dental alloys was evaluated in 34 patients by MELISA, a modified test for
      lymphocyte proliferation. In addition, cytokines in culture media were determined
      in 10 persons by the Human Inflammation Antibody Array. RESULTS: Dense particles
      containing metals were found in the matrix among collagen fibrils and in close
      proximity of the lamina basalis of the gingival epithelium. Particles were also
      localized intracellularly in fibroblasts, macrophages, and endothelial cells.
      Metallic depositions consisted predominantly of silver accompanied by selenium
      and sulphur. Twenty five out of 34 patients revealed high lymphocyte reactivity
      (positive MELISA test) to one or more metal components of dental restorations. A
      correlation between the positivity in MELISA test and number of dental alloys in
      the oral cavity was also found. Twenty MELISA positive patients suffered from
      serious health problems (various allergies, autoimmune diseases, Parkinson's
      syndrome etc.). Nickel and inorganic mercury were the most common sensitizers in
      vitro. The cytokine assay revealed that mercury chloride activated predominantly
      TH2 lymphocytes, while nickel chloride activated mainly TH1 lymphocytes.
      CONCLUSIONS: Metallic pigmentations in the oral cavity demonstrate a corrosion
      process and may pose a risk in immunologically susceptible patients.

PMID- 16892011
TI  - Survivin nuclear labeling index: a superior biomarker in superficial urothelial
      carcinoma of human urinary bladder.
AB  - The caspase family proteases are key proapoptotic proteins while the inhibitor of
      apoptosis proteins (IAP) prevent apoptosis by antagonizing the caspases or other
      key proapoptotic proteins. Limited studies of IAPs suggested their deregulation
      contributed to urothelial neoplasia. However, the expression status and biologic
      or prognostic significance of the caspase and IAP family proteins in urothelial
      neoplasms is not clear. In the present study, we first systematically evaluated
      the expression profile of the major apoptosis regulators, including caspases
      (CASP3, 6, 7, 8, 9, 10, and 14), IAPs (survivin/BIRC5, CIAP1, CIAP2, XIAP, and
      LIVIN), APAF1, SMAC, and BCL2, as well as proliferation markers Ki67 and PHH3, in
      Ta/T1 human urinary bladder urothelial carcinomas and normal urothelium samples
      by immunohistochemistry. The analysis showed that survivin/BIRC5 nuclear labeling
      index (BIRC5-N), but not cytoplasmic staining, was the only apoptotic marker
      which correlated significantly with tumor grade, stage, and patient outcome. We
      further analyzed the prognostic value of BIRC5-N in 101 Ta/T1 urinary bladder
      urothelial carcinomas by univariate analysis, which showed that BIRC5-N as well
      as the more classical prognosticators (stage, grade, and Ki67 index) were of
      prognostic significance. However, multivariate analysis by Cox proportional
      hazard regression demonstrated BIRC5-N was a stronger prognosticator than tumor
      grade, stage, and Ki67 labeling index. BIRC5-N index of 8% or more predicted
      unfavorable disease-specific survival (relative risk (RR)=6.6, 95% confidence
      interval=1.6-26.7, P=0.0080) as well as progression-free survival (RR=4.4, 95%
      confidence interval=1.3-14.6, P=0.0151). We conclude that BIRC5-N is a superior
      biologic and prognostic marker for Ta/T1 urothelial carcinomas of urinary
      bladder.

PMID- 16892012
TI  - PKCtheta expression in gastrointestinal stromal tumor.
AB  - Gastrointestinal stromal tumor is characterized by a gain of function mutation of
      KIT gene and the expression of c-kit protein, but in 5% of cases, c-kit
      expression is negative although histological findings of gastrointestinal stromal
      tumor are most suspicious. The existence of c-kit-negative gastrointestinal
      stromal tumors points to the need of additional markers for making the diagnosis.
      In this study, we studied the expression of PKCtheta and correlated their
      expression with other immunohistochemical profiles of gastrointestinal stromal
      tumors and evaluated their usability as a diagnostic marker. For this purpose,
      220 gastrointestinal stromal tumors were immunohistochemically stained for
      PKCtheta, c-kit, CD34, alpha-smooth muscle actin and S-100 protein. Additionally,
      genetic studies of KIT and PDGFRA genes were performed using c-kit-negative or
      PKCtheta-negative cases. All the 220 masses were either PKCtheta-positive or c
      kit-positive. PKCtheta was positive in 212 (96%) cases and c-kit was positive in
      216 (98%) cases in the cytoplasm of tumor cells with a diffuse staining pattern.
      Out of 212 PKCtheta-positive GISTs, 208 (98%) cases were c-kit-positive, 174
      (82%) cases were CD34-positive, 62 (29%) cases were SMA-positive and S-100
      protein was positive in 54 cases (26%). Genetic analyses on eight PKCtheta
      negative cases showed exon 11 mutations of KIT gene in four cases. Two PKCtheta
      positive and c-kit-negative GISTs showed mutations of PDGFRA gene. Our study
      shows that PKCtheta is a useful marker and it may play a role in the development
      of gastrointestinal stromal tumors. Together with c-kit, PKCtheta immunostaining
      can be used as an important diagnostic tool in the pathologic diagnosis of
      gastrointestinal stromal tumors with its high specificity and sensitivity.

PMID- 16892014
TI  - Move against malaria.

PMID- 16892015
TI  - Ambitious AIDS grants deepen rift between researchers.

PMID- 16892013
TI  - GLUT1 and GLUT8 in endometrium and endometrial adenocarcinoma.
AB  - Glucose is provided to cells by a family of glucose transport facilitators known
      as GLUTs. These transporters are expressed in a tissue specific manner and are
      overexpressed in many primary tumors of these tissues. Regulation of glucose
      transport facilitator expression has been demonstrated in endometrial tissue and
      endometrial adenocarcinoma. The following experiments were conducted to quantify
      and localize the expression of GLUT1 and GLUT8 in benign endometrium and compare
      this expression to endometrial cancer. Endometrial tissue samples were obtained
      from random hysterectomy specimens of patients with benign indications for
      surgery and endometrial cancer. Immunoblot and immunolocatization studies were
      performed using GLUT1 and GLUT8 specific antisera. Endometrial samples from 65
      women who had undergone hysterectomy were examined (n=38 benign, n=27 malignant).
      A 44 and a 35.4 kDa immunoreacive species was demonstrated in endometrium and
      endometrial cancer for GLUT1 and GLUT8, respectively. Upregulation of GLUT1
      expression was demonstrated with increasing grade of tumors (P<0.002). GLUT8
      expression was increased in all tumor subtypes compared to atrophic endometrium
      (P<0.001). Apical localization by GLUT1 and GLUT8 was demonstrated in endometrial
      glands. GLUT1 and GLUT8 demonstrated diffuse intracellular localization in the
      cancer subtypes. GLUT1 and GLUT8 are expressed in both human endometrium and
      endometrial cancer. There appears to be a step-wise progression in GLUT1 and
      GLUT8 expression as tumor histopathology worsens. GLUT1 and GLUT8 may be
      important markers in tumor differentiation, as well as providing energy to
      rapidly dividing tumor cells.

PMID- 16892017
TI  - US plan for routine HIV testing alarms privacy advocates.

PMID- 16892018
TI  - Rules murky on DNA-based identification of disaster victims.

PMID- 16892019
TI  - Frequent cases force China to face up to scientific fraud.

PMID- 16892021
TI  - DDT returns.

PMID- 16892022
TI  - Profile: Amir Attaran.

PMID- 16892024
TI  - Efomycine M: an inhibitor of selectins?

PMID- 16892025
TI  - Is cancer a disease of self-seeding?

PMID- 16892027
TI  - Targeted cancer therapeutics: the heartbreak of success.

PMID- 16892028
TI  - Embryogenesis meets tumorigenesis.

PMID- 16892029
TI  - Turning neurogenesis up a Notch.

PMID- 16892030
TI  - ALS: life and death in a bad neighborhood.

PMID- 16892031
TI  - Stopping cancer before it colonizes.

PMID- 16892032
TI  - Tyrosine kinases: maiming myelin in leprosy.

PMID- 16892033
TI  - Side effects may include evolution.

PMID- 16892035
TI  - Tumor metastasis: mechanistic insights and clinical challenges.

PMID- 16892036
TI  - Embryonic and tumorigenic pathways converge via Nodal signaling: role in melanoma
      aggressiveness.
AB  - Bidirectional cellular communication is integral to both cancer progression and
      embryological development. In addition, aggressive tumor cells are phenotypically
      plastic, sharing many properties with embryonic cells. Owing to the similarities
      between these two types of cells, the developing zebrafish can be used as a
      biosensor for tumor-derived signals. Using this system, we show that aggressive
      melanoma cells secrete Nodal (a potent embryonic morphogen) and consequently can
      induce ectopic formation of the embryonic axis. We further show that Nodal is
      present in human metastatic tumors, but not in normal skin, and thus may be
      involved in melanoma pathogenesis. Inhibition of Nodal signaling reduces melanoma
      cell invasiveness, colony formation and tumorigenicity. Nodal inhibition also
      promotes the reversion of melanoma cells toward a melanocytic phenotype. These
      data suggest that Nodal signaling has a key role in melanoma cell plasticity and
      tumorigenicity, thereby providing a previously unknown molecular target for
      regulating tumor progression.

PMID- 16892037
TI  - A previously unidentified alternatively spliced isoform of t(8;21) transcript
      promotes leukemogenesis.
AB  - The t(8;21)(q22;q22) translocation is one of the most common genetic
      abnormalities in acute myeloid leukemia (AML), identified in 15% of all cases of
      AML, including 40-50% of FAB M2 subtype and rare cases of M0, M1 and M4 subtypes.
      The most commonly known AML1-ETO fusion protein (full-length AML1-ETO) from this
      translocation has 752 amino acids and contains the N-terminal portion of RUNX1
      (also known as AML1, CBFalpha2 or PEBP2alphaB), including its DNA binding domain,
      and almost the entire RUNX1T1 (also known as MTG8 or ETO) protein. Although
      alterations of gene expression and hematopoietic cell proliferation have been
      reported in the presence of AML1-ETO, its expression does not lead to the
      development of leukemia. Here, we report the identification of a previously
      unknown alternatively spliced isoform of the AML1-ETO transcript, AML1-ETO9a,
      that includes an extra exon, exon 9a, of the ETO gene. AML1-ETO9a encodes a C
      terminally truncated AML1-ETO protein of 575 amino acids. Expression of AML1
      ETO9a leads to rapid development of leukemia in a mouse retroviral transduction
      transplantation model. More importantly, coexpression of AML1-ETO and AML1-ETO9a
      results in the substantially earlier onset of AML and blocks myeloid cell
      differentiation at a more immature stage. These results indicate that fusion
      proteins from alternatively spliced isoforms of a chromosomal translocation may
      work together to induce cancer development.

PMID- 16892039
TI  - ErbB2 receptor tyrosine kinase signaling mediates early demyelination induced by
      leprosy bacilli.
AB  - Demyelination is a common pathologic feature in many neurodegenerative diseases
      including infection with leprosy-causing Mycobacterium leprae. Because of the
      long incubation time and highly complex disease pathogenesis, the management of
      nerve damage in leprosy, as in other demyelinating diseases, is extremely
      difficult. Therefore, an important challenge in therapeutic interventions is to
      identify the molecular events that occur in the early phase before the
      progression of the disease. Here we provide evidence that M. leprae-induced
      demyelination is a result of direct bacterial ligation to and activation of ErbB2
      receptor tyrosine kinase (RTK) signaling without ErbB2-ErbB3 heterodimerization,
      a previously unknown mechanism that bypasses the neuregulin-ErbB3-mediated ErbB2
      phosphorylation. MEK-dependent Erk1 and Erk2 (hereafter referred to as Erk1/2)
      signaling is identified as a downstream target of M. leprae-induced ErbB2
      activation that mediates demyelination. Herceptin (trastuzumab), a therapeutic
      humanized ErbB2-specific antibody, inhibits M. leprae binding to and activation
      of ErbB2 and Erk1/2 in human primary Schwann cells, and the blockade of ErbB2
      activity by the small molecule dual ErbB1-ErbB2 kinase inhibitor PKI-166 (ref.
      11) effectively abrogates M. leprae-induced myelin damage in in vitro and in vivo
      models. These results may have implications for the design of ErbB2 RTK-based
      therapies for both leprosy nerve damage and other demyelinating neurodegenerative
      diseases.

PMID- 16892038
TI  - Memory T(H)2 cells induce alternatively activated macrophages to mediate
      protection against nematode parasites.
AB  - Although primary and memory responses against bacteria and viruses have been
      studied extensively, T helper type 2 (T(H)2) effector mechanisms leading to host
      protection against helminthic parasites remain elusive. Examination of the
      intestinal epithelial submucosa of mice after primary and secondary infections by
      a natural gastrointestinal parasite revealed a distinct immune-cell infiltrate
      after challenge, featuring interleukin-4-expressing memory CD4(+) T cells that
      induced IL-4 receptor(hi) (IL-4R(hi)) CD206(+) alternatively activated
      macrophages. In turn, these alternatively activated macrophages (AAMacs)
      functioned as important effector cells of the protective memory response
      contributing to parasite elimination, demonstrating a previously unknown
      mechanism for host protection against intestinal helminths.

PMID- 16892041
TI  - Exploitation of the Toll-like receptor system in cancer: a doubled-edged sword?
AB  - The toll-like receptor (TLR) system constitutes a pylogenetically ancient,
      evolutionary conserved, archetypal pattern recognition system, which underpins
      pathogen recognition by and activation of the immune system. Toll-like receptor
      agonists have long been used as immunoadjuvants in anti cancer immunotherapy.
      However, TLRs are increasingly implicated in human disease pathogenesis and an
      expanding body of both clinical and experimental evidence suggests that the
      neoplastic process may subvert TLR signalling pathways to advance cancer
      progression. Recent discoveries in the TLR system open a multitude of potential
      therapeutic avenues. Extrapolation of such TLR system manipulations to a clinical
      oncological setting demands care to prevent potentially deleterious activation of
      TLR-mediated survival pathways. Thus, the TLR system is a double-edge sword,
      which needs to be carefully wielded in the setting of neoplastic disease.

PMID- 16892043
TI  - Multivariate analysis of oestrogen receptor alpha, pS2, metallothionein and CD24
      expression in invasive breast cancers.
AB  - Determination of oestrogen receptor alpha (ER) represents at present the most
      important predictive factor in breast cancers. Data of ours and of other authors
      suggest that promising predictive/prognostic factors may also include pS2,
      metallothionein (MT) and CD24. Present study aimed at determining prognostic and
      predictive value of immunohistochemical determination of ER, pS2, MT, and CD24
      expression in sections originating from 104 patients with breast cancer. An
      univariate and multivariate analysis was performed. Both univariate and
      multivariate analyses demonstrated that cytoplasmic-membranous expression of CD24
      (CD24c-m) represents a strong unfavourable prognostic factor in the entire group
      and in most of the subgroups of patients. In several subgroups of the patients
      also a prognostic value was demonstrated of elevated expression of pS2 and of
      membranous expression of CD24. Our studies demonstrated that all patients with
      good prognostic factors (higher ER and pS2 expressions, lower MT expression,
      CD24c-m negativity) survived total period of observation (103 months). The study
      documented that cytoplasmic-membranous expression of CD24 represented an
      extremely strong unfavourable prognostic factor in breast cancer. Examination of
      the entire panel of the studied proteins permitted to select a group of patients
      of an exceptionally good prognosis.

PMID- 16892042
TI  - CD70 (TNFSF7) is expressed at high prevalence in renal cell carcinomas and is
      rapidly internalised on antibody binding.
AB  - In order to identify potential markers of renal cancer, the plasma membrane
      protein content of renal cell carcinoma (RCC)-derived cell lines was annotated
      using a proteomics process. One unusual protein identified at high levels in A498
      and 786-O cells was CD70 (TNFSF7), a type II transmembrane receptor normally
      expressed on a subset of B, T and NK cells, where it plays a costimulatory role
      in immune cell activation. Immunohistochemical analysis of CD70 expression in
      multiple carcinoma types demonstrated strong CD70 staining in RCC tissues.
      Metastatic tissues from eight of 11 patients with clear cell RCC were positive
      for CD70 expression. Immunocytochemical analysis demonstrated that binding of an
      anti-CD70 antibody to CD70 endogenously expressed on the surface of A498 and 786
      O cell lines resulted in the rapid internalisation of the antibody-receptor
      complex. Coincubation of the internalising anti-CD70 antibody with a saporin
      conjugated secondary antibody before addition to A498 cells resulted in 50% cell
      killing. These data indicate that CD70 represents a potential target antigen for
      toxin-conjugated therapeutic antibody treatment of RCC.

PMID- 16892044
TI  - Cigarette smoking, von Hippel-Lindau gene mutations and sporadic renal cell
      carcinoma.
AB  - We investigated whether smoking is associated with mutations in the Von Hippel
      Lindau (VHL) gene in 337 cases of sporadic renal cell carcinoma (RCC) among 120
      852 people followed for 11.3 years; the findings suggest that smoking causes RCC
      independently of VHL gene mutations.

PMID- 16892048
TI  - Nano-alpha-Al2O3 by liquid-feed flame spray pyrolysis.
AB  - Nanometre-sized particles of transition (t)-aluminas are important for the
      fabrication of high-quality alumina ceramics. Multiple tons are produced each
      year using a variety of gas-phase processes. The nanoparticles produced by these
      methods consist mainly of the undesired delta phase with some gamma- and theta
      Al(2)O(3). Nano-t-aluminas should provide access to dense nano/submicrometre
      grained alpha-Al(2)O(3) shapes offering significant advantages over micrometre
      grained shapes. Unfortunately, polymorphism coupled with the high activation
      energy for nucleating alpha-Al(2)O(3) greatly impedes efforts to process dense
      alpha-Al(2)O(3) with controlled grain sizes, especially for submicrometre
      materials. Typically alpha-Al(2)O(3) nucleation within t-aluminas is sporadic
      rather than uniform, leading to exaggerated grain growth and vermicular
      microstructures without full densification (5). Thus, production of quantities of
      nano-alpha-Al(2)O(3) from multiple nano-t-aluminas for seeding or direct
      processing of alpha-Al(2)O(3) monoliths could greatly change how alpha-Al(2)O(3)
      components are processed. We report here that liquid-feed flame spray pyrolysis
      of nano-t-aluminas converts them to dispersible 30-80 nm alpha-Al(2)O(3) powders
      (50-85% phase transformed). Surprisingly, the powder surfaces are fully
      dehydrated. These powders pressureless sinter to more than 99.5% dense alpha
      Al(2)O(3) with final grain sizes < or =500 nm without sintering aids.

PMID- 16892047
TI  - Transgeneration memory of stress in plants.
AB  - Owing to their sessile nature, plants are constantly exposed to a multitude of
      environmental stresses to which they react with a battery of responses. The
      result is plant tolerance to conditions such as excessive or inadequate light,
      water, salt and temperature, and resistance to pathogens. Not only is plant
      physiology known to change under abiotic or biotic stress, but changes in the
      genome have also been identified. However, it was not determined whether plants
      from successive generations of the original, stressed plants inherited the
      capacity for genomic change. Here we show that in Arabidopsis thaliana plants
      treated with short-wavelength radiation (ultraviolet-C) or flagellin (an elicitor
      of plant defences), somatic homologous recombination of a transgenic reporter is
      increased in the treated population and these increased levels of homologous
      recombination persist in the subsequent, untreated generations. The epigenetic
      trait of enhanced homologous recombination could be transmitted through both the
      maternal and the paternal crossing partner, and proved to be dominant. The
      increase of the hyper-recombination state in generations subsequent to the
      treated generation was independent of the presence of the transgenic allele (the
      recombination substrate under consideration) in the treated plant. We conclude
      that environmental factors lead to increased genomic flexibility even in
      successive, untreated generations, and may increase the potential for adaptation.

PMID- 16892049
TI  - Amphiphilic organosilane-directed synthesis of crystalline zeolite with tunable
      mesoporosity.
AB  - Zeolites are a family of crystalline aluminosilicate materials widely used as
      shape-selective catalysts, ion exchange materials, and adsorbents for organic
      compounds. In the present work, zeolites were synthesized by adding a rationally
      designed amphiphilic organosilane surfactant to conventional alkaline zeolite
      synthesis mixtures. The zeolite products were characterized by a complementary
      combination of X-ray diffraction (XRD), nitrogen sorption, scanning electron
      microscopy (SEM) and transmission electron microscopy (TEM). The analyses show
      that the present method is suitable as a direct synthesis route to highly
      mesoporous zeolites. The mesopore diameters could be uniformly tailored, similar
      to ordered mesoporous silica with amorphous frameworks. The mesoporous zeolite
      exhibited a narrow, small-angle XRD peak, which is characteristic of the short
      range correlation between mesopores, similar to disordered wormhole-like
      mesoporous materials. The XRD patterns and electron micrographs of the samples
      taken during crystallization clearly showed the evolution of the mesoporous
      structure concomitantly to the crystallization of zeolite frameworks. The
      synthesis of the crystalline aluminosilicate materials with tunable mesoporosity
      and strong acidity has potentially important technological implications for
      catalytic reactions of large molecules, whereas conventional mesoporous materials
      lack hydrothermal stability and acidity.

PMID- 16892050
TI  - Allosteric inhibition of kinesin-5 modulates its processive directional motility.
AB  - Small-molecule inhibitors of kinesin-5 (refs. 1-3), a protein essential for
      eukaryotic cell division, represent alternatives to antimitotic agents that
      target tubulin. While tubulin is needed for multiple intracellular processes, the
      known functions of kinesin-5 are limited to dividing cells, making it likely that
      kinesin-5 inhibitors would have fewer side effects than do tubulin-targeting
      drugs. Kinesin-5 inhibitors, such as monastrol, act through poorly understood
      allosteric mechanisms, not competing with ATP binding. Moreover, the microscopic
      mechanism of full-length kinesin-5 motility is not known. Here we characterize
      the motile properties and allosteric inhibition of Eg5, a vertebrate kinesin-5,
      using a GFP fusion protein in single-molecule fluorescence assays. We find that
      Eg5 is a processive kinesin whose motility includes, in addition to ATP-dependent
      directional motion, a diffusive component not requiring ATP hydrolysis. Monastrol
      suppresses the directional processive motility of microtubule-bound Eg5. These
      data on Eg5's allosteric inhibition will impact these inhibitors' use as probes
      and development as chemotherapeutic agents.

PMID- 16892051
TI  - Interactions between E2F1 and SirT1 regulate apoptotic response to DNA damage.
AB  - The nicotinamide adenine dinucleotide (NAD)-dependent deacetylase Sir2 (silent
      information regulator 2) regulates gene silencing in yeast and promotes lifespan
      extension during caloric restriction. The mammalian homologue of Sir2 (SirT1)
      regulates p53, NF-kappaB and Forkhead transcription factors, and is implicated in
      stress response. This report shows that the cell-cycle and apoptosis regulator
      E2F1 induces SirT1 expression at the transcriptional level. Furthermore, SirT1
      binds to E2F1 and inhibits E2F1 activities, forming a negative feedback loop.
      Knockdown of SirT1 by small interference RNA (siRNA) increases E2F1
      transcriptional and apoptotic functions. DNA damage by etoposide causes E2F1
      dependent induction of SirT1 expression and knockdown of SirT1 increases
      sensitivity to etoposide. These results reveal a mutual regulation between E2F1
      and SirT1 that affects cellular sensitivity to DNA damage.

PMID- 16892052
TI  - Smc5-Smc6 mediate DNA double-strand-break repair by promoting sister-chromatid
      recombination.
AB  - DNA double-strand breaks (DSB) can arise during DNA replication, or after
      exposure to DNA-damaging agents, and their correct repair is fundamental for cell
      survival and genomic stability. Here, we show that the Smc5-Smc6 complex is
      recruited to DSBs de novo to support their repair by homologous recombination
      between sister chromatids. In addition, we demonstrate that Smc5-Smc6 is
      necessary to suppress gross chromosomal rearrangements. Our findings show that
      the Smc5-Smc6 complex is essential for genome stability as it promotes repair of
      DSBs by error-free sister-chromatid recombination (SCR), thereby suppressing
      inappropriate non-sister recombination events.

PMID- 16892053
TI  - Regulation of the Raf-MEK-ERK pathway by protein phosphatase 5.
AB  - The Raf-MEK-ERK pathway couples growth factor, mitogenic and extracellular matrix
      signals to cell fate decisions such as growth, proliferation, migration,
      differentiation and survival. Raf-1 is a direct effector of the Ras GTPase and is
      the initiating kinase in this signalling cascade. Although Raf-1 activation is
      well studied, little is known about how Raf-1 is inactivated. Here, we used a
      proteomic approach to identify molecules that may inactivate Raf-1 signalling.
      Protein phosphatase 5 (PP5) was identified as an inactivator that associates with
      Raf-1 on growth factor stimulation and selectively dephosphorylates an essential
      activating site, Ser 338. The PP5-mediated dephosphorylation of Ser 338 inhibited
      Raf-1 activity and downstream signalling to MEK, an effect that was prevented by
      phosphomimetic substitution of Ser 338, or by ablation of PP5 catalytic function.
      Furthermore, depletion of endogenous PP5 increased cellular phospho-Ser 338
      levels. Our results suggest that PP5 is a physiological regulator of Raf-1
      signalling pathways.

PMID- 16892054
TI  - Examining how the spatial organization of chromatin signals influences metaphase
      spindle assembly.
AB  - During cell division, the proper assembly of a microtubule-based bipolar spindle
      depends on signals from chromatin. However, it is unknown how the spatial
      organization of chromatin signals affects spindle morphology. Here, we use
      paramagnetic chromatin beads, and magnetic fields for their alignment in cell
      free extracts, to examine the spatial components of signals that regulate spindle
      assembly. We find that for linear chromatin-bead arrays that vary by eightfold in
      length, metaphase spindle size and shape are constant. Our findings indicate
      that, although chromatin provides cues for microtubule formation, metaphase
      spindle organization, which is controlled by microtubule-based motors, is robust
      to changes in the shape of chromatin signals.

PMID- 16892055
TI  - Cool-1 functions as an essential regulatory node for EGF receptor- and Src
      mediated cell growth.
AB  - Cool-1 (cloned-out of library 1) has a key role in regulating epidermal growth
      factor receptor (EGFR) degradation. Here, we show that Cool-1 performs this
      function by functioning as both an upstream activator and downstream target for
      Cdc42. EGF-dependent phosphorylation of Cool-1 enables it to act as a nucleotide
      exchange factor for Cdc42 and to form a complex with the E3 ligase Cbl, thus
      regulating Cbl-catalysed EGFR degradation. The EGF-dependent phosphorylation is
      normally transient; however, Cool-1 phosphorylation is sustained in cells
      expressing v-Src and is essential for cellular transformation, as well as for v
      Src-induced tumour formation in mice. These findings demonstrate that the
      regulated phosphorylation of Cool-1 is necessary to maintain the balance between
      normal signalling by EGFR and Src versus aberrant growth and transformation.

PMID- 16892056
TI  - Spine growth precedes synapse formation in the adult neocortex in vivo.
AB  - Dendritic spines appear and disappear in an experience-dependent manner. Although
      some new spines have been shown to contain synapses, little is known about the
      relationship between spine addition and synapse formation, the relative time
      course of these events, or whether they are coupled to de novo growth of axonal
      boutons. We imaged dendrites in barrel cortex of adult mice over 1 month,
      tracking gains and losses of spines. Using serial section electron microscopy, we
      analyzed the ultrastructure of spines and associated boutons. Spines
      reconstructed shortly after they appeared often lacked synapses, whereas spines
      that persisted for 4 d or more always had synapses. New spines had a large
      surface-to-volume ratio and preferentially contacted boutons with other synapses.
      In some instances, two new spines contacted the same axon. Our data show that
      spine growth precedes synapse formation and that new synapses form preferentially
      onto existing boutons.

PMID- 16892057
TI  - High-resolution imaging reveals highly selective nonface clusters in the fusiform
      face area.
AB  - A region in ventral human cortex (fusiform face area, FFA) thought to be
      important for face perception responds strongly to faces and less strongly to
      nonface objects. This pattern of response may reflect a uniform face-selective
      neural population or activity averaged across populations with heterogeneous
      selectivity. Using high-resolution functional magnetic resonance imaging (MRI),
      we found that the FFA has a reliable heterogeneous structure: localized
      subregions within the FFA highly selective to faces are spatially interdigitated
      with localized subregions highly selective to different object categories. We
      found a preponderance of face-selective responses in the FFA, but no difference
      in selectivity to faces compared to nonfaces. Thus, standard fMRI of the FFA
      reflects averaging of heterogeneous highly selective neural populations of
      differing sizes, rather than higher selectivity to faces. These results suggest
      that visual processing in this region is not exclusive to faces. Overall, our
      approach provides a framework for understanding the fine-scale structure of
      neural representations in the human brain.

PMID- 16892058
TI  - The Rho-GTPase cdc42 regulates neural progenitor fate at the apical surface.
AB  - Stem cell persistence into adulthood requires self-renewal from early
      developmental stages. In the developing mouse brain, only apical progenitors
      located at the ventricle are self-renewing, whereas basal progenitors gradually
      deplete. However, nothing is known about the mechanisms regulating the
      fundamental difference between these progenitors. Here we show that the
      conditional deletion of the small Rho-GTPase cdc42 at different stages of
      neurogenesis in mouse telencephalon results in an immediate increase in basal
      mitoses. Whereas cdc42-deficient progenitors have normal cell cycle length,
      orientation of cell division and basement membrane contact, the apical location
      of the Par complex and adherens junctions are gradually lost, leading to an
      increasing failure of apically directed interkinetic nuclear migration. These
      cells then undergo mitoses at basal positions and acquire the fate of basal
      progenitors. Thus, cdc42 has a crucial role at the apical pole of progenitors,
      thereby regulating the position of mitoses and cell fate.

PMID- 16892059
TI  - JAK signaling globally counteracts heterochromatic gene silencing.
AB  - The JAK/STAT pathway has pleiotropic roles in animal development, and its
      aberrant activation is implicated in multiple human cancers. JAK/STAT signaling
      effects have been attributed largely to direct transcriptional regulation by STAT
      of specific target genes that promote tumor cell proliferation or survival. We
      show here in a Drosophila melanogaster hematopoietic tumor model, however, that
      JAK overactivation globally disrupts heterochromatic gene silencing, an
      epigenetic tumor suppressive mechanism. This disruption allows derepression of
      genes that are not direct targets of STAT, as evidenced by suppression of
      heterochromatin-mediated position effect variegation. Moreover, mutations in the
      genes encoding heterochromatin components heterochromatin protein 1 (HP1) and
      Su(var)3-9 enhance tumorigenesis induced by an oncogenic JAK kinase without
      affecting JAK/STAT signaling. Consistently, JAK loss of function enhances
      heterochromatic gene silencing, whereas overexpressing HP1 suppresses oncogenic
      JAK-induced tumors. These results demonstrate that the JAK/STAT pathway regulates
      cellular epigenetic status and that globally disrupting heterochromatin-mediated
      tumor suppression is essential for tumorigenesis induced by JAK overactivation.

PMID- 16892060
TI  - Population genomic analysis of outcrossing and recombination in yeast.
AB  - The budding yeast Saccharomyces cerevisiae has been used by humans for millennia
      to make wine, beer and bread. More recently, it became a key model organism for
      studies of eukaryotic biology and for genomic analysis. However, relatively
      little is known about the natural lifestyle and population genetics of yeast. One
      major question is whether genetically diverse yeast strains mate and recombine in
      the wild. We developed a method to infer the evolutionary history of a species
      from genome sequences of multiple individuals and applied it to whole-genome
      sequence data from three strains of Saccharomyces cerevisiae and the sister
      species Saccharomyces paradoxus. We observed a pattern of sequence variation
      among yeast strains in which ancestral recombination events lead to a mosaic of
      segments with shared genealogy. Based on sequence divergence and the inferred
      median size of shared segments (approximately 2,000 bp), we estimated that
      although any two strains have undergone approximately 16 million cell divisions
      since their last common ancestor, only 314 outcrossing events have occurred
      during this time (roughly one every 50,000 divisions). Local correlations in
      polymorphism rates indicate that linkage disequilibrium in yeast should extend
      over kilobases. Our results provide the initial foundation for population studies
      of association between genotype and phenotype in S. cerevisiae.

PMID- 16892061
TI  - Apoptosis of vascular smooth muscle cells induces features of plaque
      vulnerability in atherosclerosis.
AB  - Vascular smooth muscle cell (VSMC) apoptosis occurs in many arterial diseases,
      including aneurysm formation, angioplasty restenosis and atherosclerosis.
      Although VSMC apoptosis promotes vessel remodeling, coagulation and inflammation,
      its precise contribution to these diseases is unknown, given that apoptosis
      frequently accompanies vessel injury or alterations to flow. To study the direct
      consequences of VSMC apoptosis, we generated transgenic mice expressing the human
      diphtheria toxin receptor (hDTR, encoded by HBEGF) from a minimal Tagln (also
      known as SM22alpha) promoter. Despite apoptosis inducing loss of 50-70% of VSMCs,
      normal arteries showed no inflammation, reactive proliferation, thrombosis,
      remodeling or aneurysm formation. In contrast, VSMC apoptosis in atherosclerotic
      plaques of SM22alpha-hDTR Apoe-/- mice induced marked thinning of fibrous cap,
      loss of collagen and matrix, accumulation of cell debris and intense intimal
      inflammation. We conclude that VSMC apoptosis is 'silent' in normal arteries,
      which have a large capacity to withstand cell loss. In contrast, VSMC apoptosis
      alone is sufficient to induce features of plaque vulnerability in
      atherosclerosis. SM22alpha-hDTR Apoe-/- mice may represent an important new model
      to test agents proposed to stabilize atherosclerotic plaques.

PMID- 16892063
TI  - Exogenous control of mammalian gene expression via modulation of translational
      termination.
AB  - Here, we describe a system for the exogenous control of gene expression in
      mammalian cells that relies on the control of translational termination. To
      achieve gene regulation, we modified protein-coding sequences by introduction of
      a translational termination codon just downstream from the initiator AUG codon.
      Translation of the resulting mRNA leads to potent reduction in expression of the
      desired gene product. Expression of the gene product can be controlled by
      treating cells that express the mRNA with either aminoglycoside antibiotics or
      several nonantibiotic compounds. We show that the extent of regulation of gene
      expression can be substantial (60-fold) and that regulation can be achieved in
      the case of a variety of different genes, in different cultured cell lines and in
      primary cells in vivo. This gene regulation strategy offers significant
      advantages over existing methods for controlling gene expression and should have
      both immediate experimental application and possible clinical application.

PMID- 16892062
TI  - Decidual NK cells regulate key developmental processes at the human fetal
      maternal interface.
AB  - Human CD56(bright) NK cells accumulate in the maternal decidua during pregnancy
      and are found in direct contact with fetal trophoblasts. Several mechanisms have
      been proposed to explain the inability of NK cells to kill the semiallogeneic
      fetal cells. However, the actual functions of decidual NK (dNK) cells during
      pregnancy are mostly unknown. Here we show that dNK cells, but not peripheral
      blood-derived NK subsets, regulate trophoblast invasion both in vitro and in vivo
      by production of the interleukin-8 and interferon-inducible protein-10
      chemokines. Furthermore, dNK cells are potent secretors of an array of angiogenic
      factors and induce vascular growth in the decidua. Notably, such functions are
      regulated by specific interactions between dNK-activating and dNK-inhibitory
      receptors and their ligands, uniquely expressed at the fetal-maternal interface.
      The overall results support a 'peaceful' model for reproductive immunology, in
      which elements of innate immunity have been incorporated in a constructive manner
      to support reproductive tissue development.

PMID- 16892064
TI  - Molecular regulation of H3K4 trimethylation by ASH2L, a shared subunit of MLL
      complexes.
AB  - MLL complexes are homologs of yeast COMPASS capable of methylating histone H3
      Lys4 (H3K4). ASH2L, RbBP5 and WDR5 are conserved subunits of MLL complexes with
      homology to the Cps40/Cps60, Cps50 and Cps30 subunits of COMPASS, respectively.
      We report that ASH2L differentially regulates MLL's catalysis of H3K4
      trimethylation similarly to Cps40 and Cps60. Furthermore, WDR5 is required to
      maintain MLL complex integrity, including the stability of ASH2L within the
      complex. These findings offer insight into the molecular role of ASH2L, and by
      extension that of WDR5, in proper H3K4 trimethylation.

PMID- 16892065
TI  - Extensive functional overlap between sigma factors in Escherichia coli.
AB  - Bacterial core RNA polymerase (RNAP) must associate with a sigma factor to
      recognize promoter sequences. Escherichia coli encodes seven sigma factors, each
      believed to be specific for a largely distinct subset of promoters. Using
      microarrays representing the entire E. coli genome, we identify 87 in vivo
      targets of sigma32, the heat-shock sigma factor, and estimate that there are 120
      150 sigma32 promoters in total. Unexpectedly, 25% of these sigma32 targets are
      located within coding regions, suggesting novel regulatory roles for sigma32. The
      majority of sigma32 promoter targets overlap with those of sigma70, the
      housekeeping sigma factor. Furthermore, their DNA sequence motifs are often
      interdigitated, with RNAPsigma70 and RNAPsigma32 initiating transcription in
      vitro with similar efficiency and from identical positions. SigmaE-regulated
      promoters also overlap extensively with those for sigma70. These results suggest
      that extensive functional overlap between sigma factors is an important
      phenomenon.

PMID- 16892066
TI  - Mechanism of the receptor-catalyzed activation of heterotrimeric G proteins.
AB  - Heptahelical receptors activate intracellular signaling pathways by catalyzing
      GTP for GDP exchange on the heterotrimeric G protein alpha subunit (G alpha).
      Despite the crucial role of this process in cell signaling, little is known about
      the mechanism of G protein activation. Here we explore the structural basis for
      receptor-mediated GDP release using electron paramagnetic resonance spectroscopy.
      Binding to the activated receptor (R*) causes an apparent rigid-body movement of
      the alpha5 helix of G alpha that would perturb GDP binding at the beta6-alpha5
      loop. This movement was not observed when a flexible loop was inserted between
      the alpha5 helix and the R*-binding C terminus, which uncouples R* binding from
      nucleotide exchange, suggesting that this movement is necessary for GDP release.
      These data provide the first direct observation of R*-mediated conformational
      changes in G proteins and define the structural basis for GDP release from G
      alpha.

PMID- 16892067
TI  - Spatiotemporal regulation of the kinase Mst1 by binding protein RAPL is critical
      for lymphocyte polarity and adhesion.
AB  - RAPL, a protein that binds the small GTPase Rap1, is required for efficient
      immune cell trafficking. Here we have identified the kinase Mst1 as a critical
      effector of RAPL. RAPL regulated the localization and kinase activity of Mst1.
      'Knockdown' of the gene encoding Mst1 demonstrated its requirement for the
      induction of both a polarized morphology and integrin LFA-1 clustering and
      adhesion triggered by chemokines and T cell receptor ligation. RAPL and Mst1
      localized to vesicular compartments and dynamically translocated with LFA-1 to
      the leading edge upon Rap1 activation, suggesting a regulatory function for the
      RAPL-Mst1 complex in intracellular transport of LFA-1. Our study demonstrates a
      previously unknown function for Mst1 of relaying the Rap1-RAPL signal to induce
      cell polarity and adhesion of lymphocytes.

PMID- 16892068
TI  - Toll-like receptor-mediated regulation of zinc homeostasis influences dendritic
      cell function.
AB  - Zinc is a trace element that is essential for the function of many enzymes and
      transcription factors. Zinc deficiency results in defects in innate and acquired
      immune responses. However, little is known about the mechanism(s) by which zinc
      affects immune cell function. Here we show that stimulation with the Toll-like
      receptor 4 agonist lipopolysaccharide (LPS) altered the expression of zinc
      transporters in dendritic cells and thereby decreased intracellular free zinc. A
      zinc chelator mimicked the effects of LPS, whereas zinc supplementation or
      overexpression of the gene encoding Zip6, a zinc transporter whose expression was
      reduced by LPS, inhibited LPS-induced upregulation of major histocompatibility
      complex class II and costimulatory molecules. These results establish a link
      between Toll-like receptor signaling and zinc homeostasis.

PMID- 16892070
TI  - Heterogeneous loss of the Y chromosome in leukocyte lineages of donor origin
      after stem cell transplantation.

PMID- 16892069
TI  - Inhibition of transcription factor NF-kappaB in the central nervous system
      ameliorates autoimmune encephalomyelitis in mice.
AB  - Activation of transcription factor NF-kappaB in the central nervous system (CNS)
      has been linked to autoimmune demyelinating disease; however, it remains unclear
      whether its function is protective or pathogenic. Here we show that CNS
      restricted ablation of 'upstream' NF-kappaB activators NEMO or IKK2 but not IKK1
      ameliorated disease pathology in a mouse model of multiple sclerosis, suggesting
      that 'canonical' NF-kappaB activation in cells of the CNS has a mainly pathogenic
      function in autoimmune demyelinating disease. NF-kappaB inhibition prevented the
      expression of proinflammatory cytokines, chemokines and the adhesion molecule
      VCAM-1 from CNS-resident cells. Thus, NF-kappaB-dependent gene expression in non
      microglial cells of the CNS provides a permissive proinflammatory milieu that is
      critical for CNS inflammation and tissue damage in autoimmune demyelinating
      disease.

PMID- 16892071
TI  - Activating KIR genes are associated with CMV reactivation and survival after non
      T-cell depleted HLA-identical sibling bone marrow transplantation for malignant
      disorders.
AB  - Combinations of HLA and killer immunoglobulin-like receptors (KIR) may affect
      outcome in T-cell depleted haematopoietic stem cell transplantation (HSCT). The
      KIR gene family includes inhibitory (KIR2DL and 3DL) and activating receptors
      (KIR2DS). Ligands are HLA-C (KIR2D) and HLA-Bw4 (KIR3DL1) for inhibitory KIR and
      are still unknown for activating KIR. The impact of activating KIR genotypes from
      donor and recipient is poorly documented in HSCT outcome. Here, HLA and KIR
      genotypes were determined in 131 pairs from non-T-cell depleted HLA-identical
      sibling HSCT. No effect of 'missing KIR ligand' was detected on acute graft
      versus-host disease (GVHD), relapse, survival or infections even in myeloid
      malignancies. However, additional activating KIR genes in the donor compared to
      the recipient's genotype or an identity between donor and recipient activating
      KIR genotypes was associated with a lower transplant-related mortality (TRM)
      (P=0.005) and in a multivariate analysis with a better survival (P=0.02, HR=0.28;
      P=0.013, HR=0.29) and a lower incidence of cytomegalovirus (CMV) reactivation
      (P=0.009, HR=0.36). These data highlight the impact of donor-activating KIR genes
      on TRM, overall survival and CMV reactivation in HLA-identical sibling HSCT.

PMID- 16892072
TI  - Phase II study of unrelated cord blood transplantation for adults with high-risk
      hematologic malignancies.
AB  - Cell dose is a critical determinant of outcomes in unrelated cord blood (CB)
      transplantation. We investigated a strategy in which CB units should contain at
      least 2 x 10(7) total nucleated cells/kg of recipient weight, otherwise a second
      unit had to be added. We report the results of a study that was prematurely
      closed owing to toxicity. Patients with advanced hematologic malignancies without
      a human leukocyte antigen-matched sibling or unrelated donor were eligible.
      Conditioning regimen consisted of fludarabine and 12 Gy of total body irradiation
      (n=11), or melphalan (n=4), with antithymocyte globulin. Graft-versus-host
      disease prophylaxis was tacrolimus and methotrexate. Fifteen patients with acute
      leukemia (n=9), chronic myelogenous leukemia (n=2), multiple myeloma (n=2) and
      lymphoma (n=2) were treated; 60% had relapsed disease at transplantation. Three
      patients received double CB transplants. The 100-day and 1-year treatment-related
      mortality rates were 40 and 53%, respectively. Median time to neutrophil and
      platelet engraftment was 22 days (n=10) and 37 days (n=10), respectively. One
      patient had secondary graft failure and five patients failed to engraft. Two
      patients are alive and disease free; 4-year actuarial survival is 33 versus 0%
      for patients transplanted in remission versus in relapse. We concluded that
      disease status was the main determinant of treatment failure in this study.

PMID- 16892073
TI  - Alternative donor transplants for adult acute lymphoblastic leukaemia: a
      comparison of the three major options.
AB  - Myeloablative sibling-matched allogeneic transplantation for adult acute
      lymphoblastic leukaemia provides the best outcome, but most patients lack a
      suitable, related histocompatible donor. We reviewed three haematopoietic stem
      cell donor sources used for alternative donor transplantation pointing out
      drawbacks of these approaches including inherent selection bias. Matched
      unrelated donor allografts most often are performed in Philadelphia chromosome
      positive disease and in second complete remission (CR2); a nearly 30% event-free
      survival (EFS) can be anticipated in select patients. Transplants using
      haploidentical donors are most successful if undertaken in CR1 and CR2 and appear
      to produce EFS rates of about 25%. Limited umbilical cord blood transplant data
      suggest efficacy, but marked patient and treatment heterogeneity hamper
      conclusions. Each of these three strategies has unique potential benefits and
      disadvantages. The growing use of minimal residual disease detection may identify
      subgroups of patients unlikely to be cured by chemotherapy alone; these patients
      are candidates for upfront high-dose chemoradiotherapy and cellular
      immunotherapy. These three approaches are plagued by treatment-related mortality
      and relapse rates as high as 40%, but advances in technology and supportive care
      may make each stem cell source more feasible and efficacious.

PMID- 16892074
TI  - Adjuvant rituximab causes prolonged hypogammaglobulinaemia following autologous
      stem cell transplant for non-Hodgkin's lymphoma.
AB  - Rituximab is an anti-CD20 monoclonal antibody that has efficacy in B-cell non
      Hodgkin's lymphoma (NHL). Adjuvant immunotherapy with rituximab may reduce
      relapse rates for high-risk B-cell NHL following high-dose chemotherapy with
      autologous stem cell transplantation (SCT). However, the potential adverse
      effects of rituximab on immune reconstitution following SCT are not fully
      characterized. We performed a retrospective analysis of immunoglobulin (Ig)
      levels and peripheral blood neutrophil counts in 11 patients who received
      adjuvant rituximab following autologous SCT for B-cell NHL. Results were compared
      to a contemporaneous group of 24 patients who received an identical conditioning
      regimen and autologous SCT for lymphoma, but no adjuvant rituximab. Adjuvant
      rituximab was associated with a significantly increased incidence of
      hypogammaglobulinaemia between 12 and 24 months post-SCT, but not neutropenia.
      Despite suppression of Igs, there were no late or atypical infective
      complications attributable to rituximab.

PMID- 16892075
TI  - Has allogeneic stem cell cryopreservation been given the 'cold shoulder'? An
      analysis of the pros and cons of using frozen versus fresh stem cell products in
      allogeneic stem cell transplantation.
AB  - Donor stem cells for allogeneic transplant traditionally are collected and
      transfused 'fresh' into the recipient on the day of transplant; alternatively
      such cells can be collected in advance and cryopreserved until needed. Most
      centers favor the former approach based on theoretical concerns that
      cryopreservation and thawing may worsen clinical outcomes. Limited published data
      from single institution retrospective studies show no significant impairment of
      engraftment or reduced day 100 survival for cryopreserved bone marrow recipients.
      There are no reported outcomes for recipients of cryopreserved peripheral blood
      allografts. Use of cryopreserved stem cells is associated with a higher incidence
      of adverse events (transfusion reactions, bacterial graft contamination and
      collection of grafts which are not utilized). Conversely, use of cryopreserved
      grafts introduces a greater flexibility into a stressed healthcare system and
      results in a more streamlined experience for the donor. Some data suggest that
      transplantation with a cryopreserved product may lower the incidence of acute
      graft-versus-host disease. We compare the pros and cons of using 'fresh' versus
      cryopreserved stem cell products for allogeneic transplantation and suggest that
      the current standard of using 'fresh' products may not be warranted. We also
      suggest future areas of exploration to better elucidate this issue.

PMID- 16892077
TI  - Mitochondria in cancer.
AB  - Prominent features of cancer cells include metabolic imbalances and enhanced
      resistance to mitochondrial apoptosis. The fact that tumors rely heavily on
      glycolysis to meet their metabolic demands has been recognized since the
      beginning of the twentieth century, yet a complete elucidation of the so-called
      Warburg effect has not been achieved. Several mechanisms have been proposed to
      explain this phenomenon, including the upregulation of rate-limiting steps of
      glycolysis, the accumulation of mutations in the mitochondrial genome, the
      hypoxia-induced switch from mitochondrial respiration to glycolysis or the
      metabolic reprogramming resulting from the loss-of-function of enzymes like
      fumarate and succinate dehydrogenases. How aerobic glycolysis and apoptosis
      resistance are linked remains to be elucidated. On the one hand, these
      alterations may be acquired independently by cancer cells during multistep
      oncogenesis. On the other hand, the suppression of the intrinsic apoptotic
      program may be achieved through mechanisms that directly lead to the Warburg
      phenotype. Cancer-specific mitochondrial alterations and bioenergetics may be
      taken advantage for the development of two novel classes of antineoplastic
      agents. A first approach would target glycolysis and/or revert the Warburg
      phenomenon, whereas a second approach would aim at inducing apoptosis by
      targeting mitochondrial proteins and membranes. In both instances, encouraging
      pre-clinical results have been obtained.

PMID- 16892078
TI  - Glycolysis inhibition for anticancer treatment.
AB  - Most cancer cells exhibit increased glycolysis and use this metabolic pathway for
      generation of ATP as a main source of their energy supply. This phenomenon is
      known as the Warburg effect and is considered as one of the most fundamental
      metabolic alterations during malignant transformation. In recent years, there are
      significant progresses in our understanding of the underlying mechanisms and the
      potential therapeutic implications. Biochemical and molecular studies suggest
      several possible mechanisms by which this metabolic alteration may evolve during
      cancer development. These mechanisms include mitochondrial defects and
      malfunction, adaptation to hypoxic tumor microenvironment, oncogenic signaling,
      and abnormal expression of metabolic enzymes. Importantly, the increased
      dependence of cancer cells on glycolytic pathway for ATP generation provides a
      biochemical basis for the design of therapeutic strategies to preferentially kill
      cancer cells by pharmacological inhibition of glycolysis. Several small molecules
      have emerged that exhibit promising anticancer activity in vitro and in vivo, as
      single agent or in combination with other therapeutic modalities. The glycolytic
      inhibitors are particularly effective against cancer cells with mitochondrial
      defects or under hypoxic conditions, which are frequently associated with
      cellular resistance to conventional anticancer drugs and radiation therapy.
      Because increased aerobic glycolysis is commonly seen in a wide spectrum of human
      cancers and hypoxia is present in most tumor microenvironment, development of
      novel glycolytic inhibitors as a new class of anticancer agents is likely to have
      broad therapeutic applications.

PMID- 16892079
TI  - Mitochondrial mutations in cancer.
AB  - The metabolism of solid tumors is associated with high lactate production while
      growing in oxygen (aerobic glycolysis) suggesting that tumors may have defects in
      mitochondrial function. The mitochondria produce cellular energy by oxidative
      phosphorylation (OXPHOS), generate reactive oxygen species (ROS) as a by-product,
      and regulate apoptosis via the mitochondrial permeability transition pore
      (mtPTP). The mitochondria are assembled from both nuclear DNA (nDNA) and
      mitochondrial DNA (mtDNA) genes. The mtDNA codes for 37 genes essential of
      OXPHOS, is present in thousands of copies per cell, and has a very high mutations
      rate. In humans, severe mtDNA mutations result in multisystem disease, while some
      functional population-specific polymorphisms appear to have permitted humans to
      adapt to new environments. Mutations in the nDNA-encoded mitochondrial genes for
      fumarate hydratase and succinate dehydrogenase have been linked to uterine
      leiomyomas and paragangliomas, and cancer cells have been shown to induce
      hexokinase II which harnesses OXPHOS adenosine triphosphate (ATP) production to
      drive glycolysis. Germline mtDNA mutations at nucleotides 10398 and 16189 have
      been associated with breast cancer and endometrial cancer. Tumor mtDNA somatic
      mutations range from severe insertion-deletion and chain termination mutations to
      mild missense mutations. Surprisingly, of the 190 tumor-specific somatic mtDNA
      mutations reported, 72% are also mtDNA sequence variants found in the general
      population. These include 52% of the tumor somatic mRNA missense mutations, 83%
      of the tRNA mutations, 38% of the rRNA mutations, and 85% of the control region
      mutations. Some associations might reflect mtDNA sequencing errors, but analysis
      of several of the tumor-specific somatic missense mutations with population
      counterparts appear legitimate. Therefore, mtDNA mutations in tumors may fall
      into two main classes: (1) severe mutations that inhibit OXPHOS, increase ROS
      production and promote tumor cell proliferation and (2) milder mutations that may
      permit tumors to adapt to new environments. The former may be lost during
      subsequent tumor oxygenation while the latter may become fixed. Hence,
      mitochondrial dysfunction does appear to be a factor in cancer etiology, an
      insight that may suggest new approaches for diagnosis and treatment.

PMID- 16892080
TI  - Mitochondrial DNA mutations in human cancer.
AB  - Somatic mitochondrial DNA (mtDNA) mutations have been increasingly observed in
      primary human cancers. As each cell contains many mitochondria with multiple
      copies of mtDNA, it is possible that wild-type and mutant mtDNA can co-exist in a
      state called heteroplasmy. During cell division, mitochondria are randomly
      distributed to daughter cells. Over time, the proportion of the mutant mtDNA
      within the cell can vary and may drift toward predominantly mutant or wild type
      to achieve homoplasmy. Thus, the biological impact of a given mutation may vary,
      depending on the proportion of mutant mtDNAs carried by the cell. This effect
      contributes to the various phenotypes observed among family members carrying the
      same pathogenic mtDNA mutation. Most mutations occur in the coding sequences but
      few result in substantial amino acid changes raising questions as to their
      biological consequence. Studies reveal that mtDNA play a crucial role in the
      development of cancer but further work is required to establish the functional
      significance of specific mitochondrial mutations in cancer and disease
      progression. The origin of somatic mtDNA mutations in human cancer and their
      potential diagnostic and therapeutic implications in cancer are discussed. This
      review article provides a detailed summary of mtDNA mutations that have been
      reported in various types of cancer. Furthermore, this review offers some
      perspective as to the origin of these of mutations, their functional consequences
      in cancer development, and possible therapeutic implications.

PMID- 16892081
TI  - Succinate dehydrogenase and fumarate hydratase: linking mitochondrial dysfunction
      and cancer.
AB  - The phenomenon of enhanced glycolysis in tumours has been acknowledged for
      decades, but biochemical evidence to explain it is only just beginning to emerge.
      A significant hint as to the triggers and advantages of enhanced glycolysis in
      tumours was supplied by the recent discovery that succinate dehydrogenase (SDH)
      and fumarate hydratase (FH) are tumour suppressors and which associated, for the
      first time, mitochondrial enzymes and their dysfunction with tumorigenesis.
      Further steps forward showed that the substrates of SDH and FH, succinate and
      fumarate, respectively, can mediate a 'metabolic signalling' pathway. Succinate
      or fumarate, which accumulate in mitochondria owing to the inactivation of SDH or
      FH, leak out to the cytosol, where they inhibit a family of prolyl hydroxylase
      enzymes (PHDs). Depending on the PHD inhibited, two newly recognized pathways
      that support tumour maintenance may ensue: affected cells become resistant to
      certain apoptotic signals and/or activate a pseudohypoxic response that enhances
      glycolysis and is conveyed by hypoxia-inducible factor.

PMID- 16892082
TI  - Mitochondrial hexokinases, novel mediators of the antiapoptotic effects of growth
      factors and Akt.
AB  - Cell survival has been closely linked to both trophic growth factor signaling and
      cellular metabolism. Such couplings have obvious physiologic and pathophysiologic
      implications, but their underlying molecular bases remain incompletely defined.
      As a common mediator of both the metabolic and anti-apoptotic effects of growth
      factors, the serine/threonine kinase Akt - also known as protein kinase B or PKB 
      is capable of regulating and coordinating these inter-related processes. The
      glucose dependence of the antiapoptotic effects of growth factors and Akt plus a
      strong correlation between Akt-regulated mitochondrial hexokinase association and
      apoptotic susceptibility suggest a major role for hexokinases in these effects.
      Mitochondrial hexokinases catalyse the first obligatory step of glucose
      metabolism and directly couple extramitochondrial glycolysis to
      intramitochondrial oxidative phosphorylation, and are thus well suited to play
      this role. The ability of Akt to regulate energy metabolism appears to have
      evolutionarily preceded the capacity to control cell survival. This suggests that
      Akt-dependent metabolic regulatory functions may have given rise to glucose
      dependent antiapoptotic effects that evolved as an adaptive sensing system
      involving hexokinases and serve to ensure mitochondrial homeostasis, thereby
      coupling metabolism to cell survival. We hypothesize that the enlistment of Akt
      and hexokinase in the control of mammalian cell apoptosis evolved as a response
      to the recruitment of mitochondria to the apoptotic cascade. The central
      importance of mitochondrial hexokinases in cell survival also suggests that they
      may represent viable therapeutic targets in cancer.

PMID- 16892083
TI  - Mitochondrial factors with dual roles in death and survival.
AB  - At least in mammals, we have some understanding of how caspases facilitate
      mitochondria-mediated cell death, but the biochemical mechanisms by which other
      factors promote or inhibit programmed cell death are not understood. Moreover,
      most of these factors are only studied after treating cells with a death
      stimulus. A growing body of new evidence suggests that cell death regulators also
      have 'day jobs' in healthy cells. Even caspases, mitochondrial fission proteins
      and pro-death Bcl-2 family proteins appear to have normal cellular functions that
      promote cell survival. Here, we review some of the supporting evidence and
      stretch beyond the evidence to seek an understanding of the remaining questions.

PMID- 16892084
TI  - Mitochondria and cancer: is there a morphological connection?
AB  - Mitochondria are key players in several cellular functions including growth,
      division, energy metabolism, and apoptosis. The mitochondrial network undergoes
      constant remodelling and these morphological changes are of direct relevance for
      the role of this organelle in cell physiology. Mitochondrial dysfunction
      contributes to a number of human disorders and may aid cancer progression. Here,
      we summarize the recent contributions made in the field of mitochondrial dynamics
      and discuss their impact on our understanding of cell function and tumorigenesis.

PMID- 16892085
TI  - The many shapes of mitochondrial death.
AB  - Mitochondria integrate apoptotic signalling by releasing cytochrome c and other
      proapoptotic cofactors needed for activation of effector caspases. Previously
      overlooked morphological changes, mitochondrial fragmentation and cristae
      remodelling, emerged as subroutines of the mitochondrial programme of apoptosis
      in mammalian cells, as well as in developmental cell death of Caenorhabditis
      elegans. Mitochondrial morphology results from fusion and fission processes,
      controlled by a growing set of 'mitochondria-shaping' proteins. Their levels and
      function appear to influence mitochondrial pathways of cell death, but mechanisms
      are largely unknown. An emerging model implicates different signals converging on
      mitochondria-shaping proteins to activate or deactivate them during apoptosis. In
      turn, these proteins can orchestrate changes in mitochondrial shape to insure
      cytochrome c release and progression of the apoptotic cascade. These therefore
      appear an appealing novel therapeutic target to modulate cell death in cancer.

PMID- 16892086
TI  - p53 and Nur77/TR3 - transcription factors that directly target mitochondria for
      cell death induction.
AB  - The complex apoptotic functions of the p53 tumor suppressor are central to its
      antineoplastic activity in vivo. Conversely, p53 function is altered or
      attenuated in one way or another in the majority of human cancers. Besides its
      well-understood action as a transcriptional regulator of multiple apoptotic
      genes, p53 also exerts a direct pro-apoptotic role at the mitochondria by
      engaging in protein-protein interactions with anti- and pro-apoptotic Bcl2 family
      members, thereby executing the shortest known circuitry of p53 death signaling.
      Nur77, also known as TR3 or NGFI-B, is a unique transcription factor belonging to
      the orphan nuclear receptor superfamily. Even more extreme than p53, Nur77 can
      exert opposing biological activities of survival and death. Its activities are
      regulated by subcellular distribution, expression levels, protein modification
      and heterodimerization with retinoid X receptor. In cancer cells, Nur77 functions
      in the nucleus as an oncogenic survival factor, but becomes a potent killer when
      certain death stimuli induce its migration to mitochondria, where it binds to
      Bcl2 and conformationally converts it to a killer that triggers cytochrome c
      release and apoptosis. This review focuses on their unexpected transcription
      independent pro-death programs at mitochondria and highlights the remarkable
      mechanistic similarities between them. Moreover, an accumulating body of evidence
      provides ample rationale to further investigate how these mitochondrial p53 and
      Nur77 pathways could become exploitable targets for new cancer therapeutics.

PMID- 16892087
TI  - The permeability transition pore complex in cancer cell death.
AB  - The permeability transition pore (PTP) is a multi-protein complex at contact
      sites of the inner with the outer mitochondrial membrane. Research over the past
      years has led to the concept that the PTP occupies a central role in cell death
      induction. Numerous apoptosis signals convert this protein aggregate into an
      unspecific pore, thus activating mitochondria for the cellular self-destruction
      process. Here, we describe the evidence for this and the various approaches being
      undertaken to elucidate its subunit composition and mode of regulation. In
      particular, we review data that indicate a role of specific PTP subunits for
      apoptosis inhibition during tumorigenesis.

PMID- 16892088
TI  - Mitochondria in hematopoiesis and hematological diseases.
AB  - Mitochondria are involved in hematopoietic cell homeostasis through multiple ways
      such as oxidative phosphorylation, various metabolic processes and the release of
      cytochrome c in the cytosol to trigger caspase activation and cell death. In
      erythroid cells, the mitochondrial steps in heme synthesis, iron (Fe) metabolism
      and Fe-sulfur (Fe-S) cluster biogenesis are of particular importance. Mutations
      in the specific delta-aminolevulinic acid synthase (ALAS) 2 isoform that
      catalyses the first and rate-limiting step in heme synthesis pathway in the
      mitochondrial matrix, lead to ineffective erythropoiesis that characterizes X
      linked sideroblastic anemia (XLSA), the most common inherited sideroblastic
      anemia. Mutations in the adenosine triphosphate-binding cassette protein ABCB7,
      identified in XLSA with ataxia (XLSA-A), disrupt the maturation of cytosolic (Fe
      S) clusters, leading to mitochondrial Fe accumulation. In addition, large
      deletions in mitochondrial DNA, whose integrity depends on a specific DNA
      polymerase, are the hallmark of Pearson's syndrome, a rare congenital disorder
      with sideroblastic anemia. In acquired myelodysplastic syndromes at early stage,
      exacerbation of physiological pathways involving caspases and the mitochondria in
      erythroid differentiation leads to abnormal activation of a mitochondria-mediated
      apoptotic cell death pathway. In contrast, oncogenesis-associated changes at the
      mitochondrial level can alter the apoptotic response of transformed hematopoietic
      cells to chemotherapeutic agents. Recent findings in mitochondria metabolism and
      functions open new perspectives in treating hematopoietic cell diseases, for
      example various compounds currently developed to trigger tumor cell death by
      directly targeting the mitochondria could prove efficient as either cytotoxic
      drugs or chemosensitizing agents in treating hematological malignancies.

PMID- 16892089
TI  - Contribution of somatic mutations in the mitochondrial genome to the development
      of cancer and tolerance against anticancer drugs.
AB  - Mitochondrial defects have long been suspected to play an important role in the
      development of cancer. Although most cancer cells harbor somatic mutations in
      mitochondrial DNA (mtDNA), the question of whether such mutations positively
      contribute to the development of cancer remained unclear. To clarify the role of
      mutant mtDNA excluding effects by the nuclear background, we focus on a method of
      transmitochondrial cybrids. Tumors were formed by transplanting cybrids with or
      without mutant mtDNA into nude mice and compared each size, revealing that mutant
      cybrids enhanced tumorigenesis. Next, we discuss a method for excluding the
      possibility of secondary nuclear mutations that may affect tumorigenesis.
      Mitochondrial genes that had been converted from mitochondrial to nuclear codons
      and equipped with a mitochondrial-targeting sequence were introduced into the
      nucleus of mutant cybrids. The gene products complemented the dysfunction, and
      reduced the promotion of tumors. By these methods, we concluded that mutant
      mitochondria positively and directly contribute to tumorigenesis. Since apoptosis
      occurred less frequently in the mutant versus wild-type cybrids in tumors,
      pathogenic mtDNA mutations contribute to the promotion of tumors by preventing
      apoptosis. Finally, we discuss the role of mutant mtDNA in conferring tolerance
      against anticancer drugs.

PMID- 16892090
TI  - Hexokinase II: cancer's double-edged sword acting as both facilitator and
      gatekeeper of malignancy when bound to mitochondria.
AB  - A key hallmark of many cancers, particularly the most aggressive, is the capacity
      to metabolize glucose at an elevated rate, a phenotype detected clinically using
      positron emission tomography (PET). This phenotype provides cancer cells,
      including those that participate in metastasis, a distinct competitive edge over
      normal cells. Specifically, after rapid entry of glucose into cancer cells on the
      glucose transporter, the highly glycolytic phenotype is supported by hexokinase
      (primarily HK II) that is overexpressed and bound to the outer mitochondrial
      membrane via the porin-like protein voltage-dependent anion channel (VDAC). This
      protein and the adenine nucleotide transporter move ATP, newly synthesized by the
      inner membrane located ATP synthase, to active sites on HK II. The abundant
      amounts of HK II bind both the ATP and the incoming glucose producing the product
      glucose-6-phosphate, also at an elevated rate. This critical metabolite then
      serves both as a biosynthetic precursor to support cell proliferation and as a
      precursor for lactic acid, the latter exiting cancer cells causing an unfavorable
      environment for normal cells. Although helping facilitate this chemical warfare,
      HK II via its mitochondrial location also suppresses the death of cancer cells,
      thus increasing their possibility for metastasis and the ultimate death of the
      human host. For these reasons, targeting this key enzyme is currently being
      investigated in several laboratories in a strategy to develop novel therapies
      that may turn the tide on the continuing struggle to find effective cures for
      cancer. One such candidate is 3-bromopyruvate that has been shown recently to
      eradicate advanced stage, PET positive hepatocellular carcinomas in an animal
      model without apparent harm to the animals.

PMID- 16892091
TI  - Mitochondriotoxic compounds for cancer therapy.
AB  - One of the hallmarks of cancer cells is their increased resistance to apoptosis
      induction. Alterations in many apoptosis regulators belonging to the intrinsic
      pathway confer emerging neoplastic cells with a selective growth advantage in the
      hostile tumor microenvironment. The realization that those same defects
      contribute to resistance to radiation and chemotherapeutic agents have prompted
      the unrelenting search for mitochondria-targeted compounds for the treatment of
      cancer. Mitochondria play a central role in the process of cell death. They serve
      as integrators of upstream effector mechanisms. Most importantly, mitochondrial
      outer membrane permeabilization becomes a commitment point during cell death.
      Thus, strategies aimed at directly triggering this event by either blocking the
      activity of antiapoptotic factors or by interfering with vital mitochondrial
      functions may help to overcome resistance to standard cancer therapy.

PMID- 16892092
TI  - Extrinsic versus intrinsic apoptosis pathways in anticancer chemotherapy.
AB  - Apoptosis or programmed cell death is a key regulator of physiological growth
      control and regulation of tissue homeostasis. One of the most important advances
      in cancer research in recent years is the recognition that cell death mostly by
      apoptosis is crucially involved in the regulation of tumor formation and also
      critically determines treatment response. Killing of tumor cells by most
      anticancer strategies currently used in clinical oncology, for example,
      chemotherapy, gamma-irradiation, suicide gene therapy or immunotherapy, has been
      linked to activation of apoptosis signal transduction pathways in cancer cells
      such as the intrinsic and/or extrinsic pathway. Thus, failure to undergo
      apoptosis may result in treatment resistance. Understanding the molecular events
      that regulate apoptosis in response to anticancer chemotherapy, and how cancer
      cells evade apoptotic death, provides novel opportunities for a more rational
      approach to develop molecular-targeted therapies for combating cancer.

PMID- 16892093
TI  - Mitochondria as therapeutic targets for cancer chemotherapy.
AB  - Mitochondria are vital for cellular bioenergetics and play a central role in
      determining the point-of-no-return of the apoptotic process. As a consequence,
      mitochondria exert a dual function in carcinogenesis. Cancer-associated changes
      in cellular metabolism (the Warburg effect) influence mitochondrial function, and
      the invalidation of apoptosis is linked to an inhibition of mitochondrial outer
      membrane permeabilization (MOMP). On theoretical grounds, it is tempting to
      develop specific therapeutic interventions that target the mitochondrial
      Achilles' heel, rendering cancer cells metabolically unviable or subverting
      endogenous MOMP inhibitors. A variety of experimental therapeutic agents can
      directly target mitochondria, causing apoptosis induction. This applies to a
      heterogeneous collection of chemically unrelated compounds including positively
      charged alpha-helical peptides, agents designed to mimic the Bcl-2 homology
      domain 3 of Bcl-2-like proteins, ampholytic cations, metals and steroid-like
      compounds. Such MOMP inducers or facilitators can induce apoptosis by themselves
      (monotherapy) or facilitate apoptosis induction in combination therapies,
      bypassing chemoresistance against DNA-damaging agents. In addition, it is
      possible to design molecules that neutralize inhibitor of apoptosis proteins
      (IAPs) or heat shock protein 70 (HSP70). Such IAP or HSP70 inhibitors can mimic
      the action of mitochondrion-derived mediators (Smac/DIABLO, that is, second
      mitochondria-derived activator of caspases/direct inhibitor of apoptosis-binding
      protein with a low isoelectric point, in the case of IAPs; AIF, that is apoptosis
      inducing factor, in the case of HSP70) and exert potent chemosensitizing effects.

PMID- 16892094
TI  - Systemic management of bladder cancer in Egypt: revisited.
AB  - Bladder cancer is still the most frequent malignant tumor among Egyptian males.
      It has a peculiar biologic, clinico-pathologic features and responsiveness to
      chemotherapy profile than that observed in Western countries. The current review
      aims to demonstrate the present state-of- art in using systemic therapy as part
      of the management options available to treat such patients at different stages of
      their disease. Individualizing therapy for these patients based on more rationale
      basis is the challenge that oncologists must face in the near future.

PMID- 16892095
TI  - How to write an oncology manuscript.
AB  - Publications may represent accomplishment in academic medicine, primary
      documentation of research data, evidence of expertise through writing an
      authoritative review paper or book chapter or a major determinant in achieving
      academic promotion and career development. Editors and reviewers appreciate
      receiving manuscripts that are easy to read and edit. Much of the information in
      journals instructions to authors is designed to accomplish that goal in ways that
      meet each journal's particular editorial needs. The CONsolidated Standards of
      Reporting Trial (CONSORT) statement is an important research tool that takes an
      evidence-based approach to improve the quality of reports of randomized trials.
      The guidance that follows provides a general background and rationale for
      preparing oncology manuscripts for any journal. Many of these guidelines are
      based on feedback provided by actual peer reviewers. Even before you start
      writing, it is good practice to review the typical sections of a manuscript The
      text of observational and experimental articles is usually (but not necessarily)
      divided into sections with the headings Introduction, Methods, Results, and
      Discussion. This so-called "IMRAD". The abstract of the manuscript is usually
      divided into background, purpose, patients and methods, results and conclusion.
      The section on patients and methods of an oncology manuscript should include the
      eligibility criteria for the patients, study design, treatment plan, baseline and
      treatment assessments and statistical analysis. The results include data on
      patient characteristics, tumor response, time to event measures, toxicity and
      dose administration. The conclusion must address the primary objective of the
      study. Authors will be able to address up front many issues regarding content,
      organization, presentation, and formatting, thereby increasing the likelihood of
      successful publication of their papers in peer-reviewed journals.

PMID- 16892097
TI  - Short questions for surveys about bread and cereal intake: comparing measures of
      quantity versus frequency.

PMID- 16892096
TI  - Automated geocoding of routinely collected health data in New South Wales.

PMID- 16892098
TI  - A tuberculosis contact investigation involving two private nursing homes in inner
      western Sydney in 2004.

PMID- 16892099
TI  - The changing epidemiology of pertussis in the Hunter New England area and
      potential implications for the immunisation schedule.

PMID- 16892100
TI  - Laboratory diagnosis of communicable diseases--pitfalls and prospects.

PMID- 16892102
TI  - Communicable diseases report, New South Wales, for January and February 2006.

PMID- 16892101
TI  - Malaria.

PMID- 16892103
TI  - Measuring the absolute photodetection efficiency using photon number
      correlations.
AB  - We present two methods for determining the absolute detection efficiency of
      photon-counting detectors directly from their singles rates under illumination
      from a nonclassical light source. One method is based on a continuous variable
      analog to coincidence counting in discrete photon experiments, but it does not
      actually rely on high detector time resolutions. The second method is based on
      difference detection, which is a typical detection scheme in continuous variable
      quantum optics experiments. Since no coincidence detection is required with
      either method, they are useful for detection efficiency measurements of
      photodetectors with detector time resolutions far too low to resolve coincidence
      events.

PMID- 16892104
TI  - Design and simulation of resonant cavity enhanced corrugated quantum well
      infrared photodetectors.
AB  - The dipole selection rule limits the maximum achievable efficiency in corrugated
      quantum well infrared photodetectors (C-QWIPs) to 50%. We consider what is
      believed to be a novel design that utilizes a resonant cavity enhancement
      technique to increase the efficiency beyond 50% by rotating the photon
      polarization at each pass around the cavity. Simulation results show that the
      quantum efficiency of this device can be enhanced up to 38% compared to that of
      the standard C-QWIP device.

PMID- 16892105
TI  - Surface-mount sapphire interferometric temperature sensor.
AB  - A fiber-optic high-temperature sensor is demonstrated by bonding a 45 degrees 
      polished single-crystal sapphire fiber on the surface of a sapphire wafer, whose
      optical thickness is temperature dependent and measured by white-light
      interferometry. A novel adhesive-free coupling between the silica and sapphire
      fibers is achieved by fusion splicing, and its performance is characterized. The
      sensor's interference signal is investigated for its dependence on angular
      alignment between the fiber and the wafer. A prototype sensor is tested to 1,170
      degrees C with a resolution of 0.4 degrees C, demonstrating excellent potential
      for high-temperature measurement.

PMID- 16892106
TI  - Improvement of accuracy in digital holography by use of multiple holograms.
AB  - Speckle pattern decorrelation reduces the accuracy of interferometric shape and
      deformation measurements. We introduce a technique for the reduction of speckle
      noise in digital holography. The method is not based on classical filtering
      techniques such as median filters. Instead it utilizes the shift theorem of the
      Fourier transform. For this method several holograms of the same object under
      test are recorded. The reconstruction leads to a set of object wave fields with
      different speckle patterns. A proper averaging procedure, taking into account the
      properties of the wrapped phases, leads to an improvement of the accuracy in the
      resulting phase difference. The theory of the applied method is described and our
      first results for technical components with an improvement of accuracy up to 1/57
      of the wavelength are presented.

PMID- 16892107
TI  - Measurement technique for in situ characterizing aberrations of projection optics
      in lithographic tools.
AB  - As the feature size decreases, degradation of image quality caused by wavefront
      aberrations of projection optics in lithographic tools has become a serious
      problem in the low-k1 process. We propose a novel measurement technique for in
      situ characterizing aberrations of projection optics in lithographic tools.
      Considering the impact of the partial coherence illumination, we introduce a
      novel algorithm that accurately describes the pattern displacement and focus
      shift induced by aberrations. Employing the algorithm, the measurement condition
      is extended from three-beam interference to two-, three-, and hybrid-beam
      interferences. The experiments are performed to measure the aberrations of
      projection optics in an ArF scanner.

PMID- 16892108
TI  - Spectral response variation of a negative-electron-affinity photocathode in the
      preparation process.
AB  - In order to research the spectral response variation of a negative electron
      affinity (NEA) photocathode in the preparation process, we have done two
      experiments on a transmission-type GaAs photocathode. First, an automatic
      spectral response recording system is described, which is used to take spectral
      response curves during the activation procedure of the photocathode. By this
      system, the spectral response curves of a GaAs:Cs-O photocathode measured in situ
      are presented. Then, after the cathode is sealed with a microchannel plate and a
      fluorescence screen into the image tube, we measure the spectral response of the
      tube by another measurement instrument. By way of comparing and analyzing these
      curves, we can find the typical variation in spectral-responses. The reasons for
      the variation are discussed. Based on these curves, spectral matching factors of
      a GaAs cathode for green vegetation and rough concrete are calculated. The visual
      ranges of night-vision goggles under specific circumstances are estimated. The
      results show that the spectral response of the NEA photocathode degraded in the
      sealing process, especially at long wavelengths. The variation has also
      influenced the whole performance of the intensifier tube.

PMID- 16892109
TI  - Localized measurement of the optical thickness of a transparent window:
      application to the study of the photosensitivity of organic polymers.
AB  - The development of an optical setup that permits us to carry out high-resolution
      mappings of the absolute optical thickness of plane-parallel transparent windows
      is described. This measurement is based on the recording and processing of the
      spectral transmission of the wafer between 1,520 and 1,570 nm and has a relative
      precision better than 10(-6). Hence it is used for the characterization of the
      photosensitivity of two organic photopolymers (cationic ring opening polymer and
      poly(methylmethacrylate)). The refractive index change dynamics for both
      materials and the spontaneous evolution of the optical thickness are
      demonstrated.

PMID- 16892110
TI  - Predicting phase steps in phase-shifting interferometry in the presence of noise
      and harmonics.
AB  - A novel method for estimating pixelwise phase step values in phase-shifting
      interferometry is presented. The method is based on the linear prediction
      property of the intensity fringes recorded temporally at a pixel on the charged
      coupled device. The salient features of the method lie in their ability to handle
      linear miscalibration errors, to compensate for the presence of harmonics in an
      optical configuration and detector nonlinearity, and to allow for the use of
      arbitrary phase steps. The robustness of the proposed method is studied in the
      presence of noise and a comparison with several benchmarking algorithms is
      performed. The simulation results show the efficiency of the algorithm in
      retrieving the wrapped phase.

PMID- 16892111
TI  - Design and demonstration of direct UV-written small angle X couplers in silica-on
      silicon for broadband operation.
AB  - Experimental demonstration of small angle (0.8 degrees-5 degrees ) direct UV
      written X couplers in silica-on-silicon is presented. Maximum and minimum
      coupling ratios of 95%(+/-0.8%) and 1.9% (+/-1%), respectively, were recorded.
      The structures also display very low polarization and wavelength dependence. A
      typical excess loss of 1.0 dB(+/-0.5 dB) was recorded. Device modeling using the
      beam propagation method and an analytical model showed good agreement with
      experimental results over a broad crossing angle and wavelength range.

PMID- 16892112
TI  - Quasi-null lens optical system for the fabrication of an oblate convex
      ellipsoidal mirror: application to the Wide Angle Camera of the Rosetta space
      mission.
AB  - The design of a quasi-null lens system for the fabrication of an aspheric oblate
      convex ellipsoidal mirror is presented. The Performance and tolerance of the
      system have been analyzed. The system has been applied successfully for the
      fabrication of the primary mirror of the Wide Angle Camera (WAC), the imaging
      system onboard the Rosetta, the European Space Agency cornerstone mission
      dedicated to the exploration of a comet. The WAC is based on an off-axis two
      mirror configuration, in which the primary mirror is an oblate convex ellipsoid
      with a significant conic constant.

PMID- 16892113
TI  - Calculating petal tools by using genetic algorithms.
AB  - To pass from a spherical surface to a conic one, it is possible to use a petal
      tool or a small solid tool that is placed at different time intervals at several
      radial zones of the glass. Genetic algorithms are applied to calculate the
      angular sizes of the incomplete annular tools that make up the petal tools. We
      also present the desired wear results carried out with the petal tool that was
      designed on the basis of the dwell times of complete annular tools. These dwell
      times are calculated by using base functions that are generated with annular
      tools and by applying the genetic algorithms.

PMID- 16892114
TI  - Diffractive-refractive hybrid corrector for achro- and apochromatic corrections
      of optical systems.
AB  - The possibility is shown of achro- and apochromatic correction of an optical
      system with any residual chromatism by completing the system with a diffractive
      refractive hybrid corrector comprising one diffractive lens and one or two
      refractive lenses.

PMID- 16892115
TI  - Long-period grating refractive index sensor with a modified cladding structure
      for large operational range and high sensitivity.
AB  - What is believed to be a novel long-period grating (LPG) refractive index sensor
      with a modified cladding structure is proposed and studied. In the proposed
      structure, the cladding of the fiber has a two-layer structure, i.e., a cladding
      layer of low refractive index with a reduced radius and an overlay of high
      refractive index. The sensitivity of the structure-modified LPG sensor to the
      ambient refractive index change as a function of the cladding layer and overlay
      parameters is investigated by way of modeling. It is found that an increase of
      the ambient refractive index causes a field redistribution of the cladding mode
      into the overlay when the parameters of the overlay are properly selected. It is
      shown that by reducing the radius of the cladding layer, the operational range of
      the LPG refractive index sensor can be as large as 0.195 (from 1.244 to 1.440)
      with a minimum sensitivity of 660 nm/refractive index, which represents a 31%
      increase of operational range in comparison with the operational range obtained
      from the reported structure. The design guidelines for achieving this large
      operation range and high sensitivity are explained by investigating the
      dependence of the cladding modes on the radius of the cladding layer.

PMID- 16892116
TI  - Shift-invariant real-time edge-enhanced VanderLugt correlator using video-rate
      compatible photorefractive polymer.
AB  - We demonstrated a real-time shift-invariant VanderLugt correlator (VLC). The VLC
      was implemented with a 37 microm thick bis-triarylamine side-chain polymer matrix
      photorefractive (PR) polymer composite operating at 532 nm wavelength.
      Correlation selectivity was enhanced by real-time edge enhancement. The advantage
      of the VLC is that its architecture allows overcoming the PR material response
      speed. A correlator of this type enables a fast shift-invariant search of a large
      optical image database. A high degree of shift invariance in our correlator was
      possible because of the material thickness. The angular bandwidth of this
      material was measured experimentally in a degenerate four-wave mixing setup, and
      it was found to be in a very good agreement with the theory.

PMID- 16892117
TI  - Flash light detection and ranging range accuracy limits for returns from single
      opaque surfaces via Cramer-Rao bounds.
AB  - A Cramer-Rao lower bound on the range accuracy obtainable by a Flash light
      detection and ranging (LADAR) system receiving a return from a single surface in
      the instantaneous field of view of each detector is developed and verified with
      experimental data. The bound is compared to the performance of a new algorithm
      and that of a matched filter receiver by using both simulated and measured LADAR
      data. The simulated data are used to show that the estimator is nearly unbiased
      and efficient for systems that match the negative paraboloid model used in its
      derivation. It is found that the achievable range accuracy for the LADAR system
      and for the target geometry used to collect the measured data is of the order of
      2.5 in. while the bound predicts a range accuracy limit of approximately 0.6 in.

PMID- 16892118
TI  - Connector-induced offsets in optical fiber powermeters.
AB  - We discuss issues related to calibration of optical fiber powermeters. The power
      readings may vary when using various types of fiber connectors, or even the same
      type of connectors made by different vendors. We study the connector effects by
      calibrating four types of optical fiber powermeters using six different fiber
      connectors from four vendors at three wavelengths. We found variations of as much
      as 12% due to the different reflection properties of the detector windows,
      connectors, and detectors. We also compared connector measurement results with
      the data obtained by using open beams.

PMID- 16892119
TI  - Moderate-to-high optical-isolation reconfigurable 1 x 2 fiber-optic add-drop
      switches using a dense wavelength division multiplexing thin-film filter.
AB  - We propose and experimentally demonstrate thin-film filter- (TF) based
      reconfigurable 1 x 2 fiber-optic add-drop switch (FADS) structures. Our key idea
      is to locate a movable mirror oriented at a desired angle near the TF to switch
      the desired wavelength optical beams to the wanted switching ports. Our first
      moderate-optical-isolation TF-based reconfigurable 1 x 2 FADS is in a
      transmissive design. Another TF-based reconfigurable 1 x 2 FADS structure is in a
      retroreflective configuration, and it gives a very low optical-coherent cross
      talk. Our experimental proof of concept using an off-the-shelf four-cavity TF
      measured center wavelength at 1,545.749 nm and a 0.8 mm x 0.8 mm x 0.15 mm
      movable mirror confirms a -19 dB and a much improved <-53 dB optical-coherent
      cross talk for our transmissive and retroreflective configurations, respectively.

PMID- 16892120
TI  - Performance analysis of a wavelength-locked Fabry-Perot laser diode by light
      injection of an external spectrally sliced Fabry-Perot laser diode.
AB  - We have analyzed and experimentally demonstrated the performance of a wavelength
      locked Fabry-Perot laser diode (FP-LD) with a spectrally sliced FP-LD as an
      external-injection optical source. A high side-mode suppression ratio exceeding
      30 dB was obtained, and the noise characteristic of the wavelength-locked FP-LD
      was analyzed in terms of both mode partition noise and interferometric noise. The
      measured relative intensity noise had a minimum value of -140 dB/Hz. We also
      investigated the transmission characteristics such as the Q factor and extinction
      ratio for a 622 Mbits/s and 2.5 Gbits/s baseband digital signal.

PMID- 16892121
TI  - Pulsed laser photofragment emission for detection of mercuric chloride.
AB  - The viability of pulsed laser photofragment emission (PFE) is evaluated for the
      in situ measurement of vapor-phase mercuric chloride (HgCl(2)) concentration in
      combustion flue gas. Dispersed emissions from both the Hg (6(3)P(1)) and HgCl
      (B(2)Sigma(+)) photoproducts are presented, and the dependence of the HgCl(2) PFE
      signal originating from Hg (6(3)P(1)) on the collisional environment is examined
      for buffer-gas mixtures of N(2), O(2), and CO(2). Integrated PFE intensity
      measurements as a function of buffer gas pressure support the assumption that the
      primary effect of the relevant flue gas constituents is to quench emission from
      Hg (6(3)P(1)). The quenching rate constants for PFE from HgCl(2) were measured to
      be 1.37 (+/-0.16) x 10(5) Torr(-1) s(-1) for N(2), 9.35 (+/-0.25) x 10(6) Torr(
      1) s(-1) for O(2), and 1.49 (+/-0.29) x 10(6) Torr(-1) s(-1) for CO(2). These
      values are in good accord with literature values for the quenching of Hg
      (6(3)P(1)). The emission cross section for Hg (6(3)P(1)) generated by
      photodissociation of HgCl(2) in 760 Torr N(2) is found to be 1.0 (+/-0.2) x 10(
      25) m(2) by comparing the PFE signal to N(2) Raman scattering.

PMID- 16892122
TI  - Bichromatic, phase compensating interferometer based on prism pair compressors.
AB  - We present a bichromatic prism pair interferometer (BPPI) for controlling the
      delay between laser pulses of two different frequencies propagating collinearly
      in a single beam. The BPPI is especially useful when working with ultrafast laser
      pulses because it intrinsically allows for independent control over the second
      order dispersion experienced by the differently colored pulses. We use this
      control to demonstrate successful precompensation for blue (lambda approximately
      390 nm) and UV (lambda approximately 260 nm) pulses that pass through 2.2 cm of
      dispersive material after the interferometer. The BPPI is extremely flexible and
      works with all frequencies from the UV to the near-infrared. We demonstrate this
      by describing measurements made with BPPIs configured for three different
      combinations of central frequencies.

PMID- 16892123
TI  - Field localization in very small aperture lasers studied by apertureless near
      field microscopy.
AB  - Localized surface plasmon polaritons (SSPs) have been observed on very small
      aperture lasers using apertureless near-field microscopy. Fields around multiple
      apertures are shown to result from interferences of SPP point sources at each
      aperture and optical fields. The near-field optical pattern around a single
      aperture indicates the interference of SPPs with their scattered counterparts.
      Near-field measurements also confirmed a preferred orientation of the rectangular
      aperture waveguide for the signal localization in very small aperture lasers.

PMID- 16892124
TI  - Pulsed Raman fiber laser and multispectral imaging in three dimensions.
AB  - Raman scattering in single-mode optical fibers is exploited to generate
      multispectral light from a green nanolaser with high pulse repetition rate. Each
      pulse triggers a picosecond camera and measures the distance by time-of-flight in
      each of the 0.5 Mpixels. Three-dimensional images are then constructed with
      submillimeter accuracy for all visible colors. The generation of a series of
      Stokes peaks by Raman scattering in a Si fiber is discussed in detail and the
      laser radar technique is demonstrated. The data recording takes only a few
      seconds, and the high accuracy 3D color imaging works at ranges up to
      approximately 200 m. Applications for optical tomography in highly scattering
      media such as water and human tissue are mentioned.

PMID- 16892125
TI  - Different cooling configurations for a high average power longitudinally diode
      pumped Yb:YAG amplifier.
AB  - We analyze the temperature distribution in several Yb:YAG longitudinally pumped
      amplifier crystals by using various cooling configurations. The crystal designs
      are (i) a composite crystal made of a thin sheet of high-doped Yb:YAG bonded on a
      bulk piece of undoped YAG and (ii) a thick piece of low-doped Yb:YAG crystal. The
      cooling configurations investigated here include those both from the rear face or
      from the rear and side faces together. In every case we determine the average
      temperature rise, the longitudinal and radial temperature gradient, and the
      resulting crystal bending and optical phase distortion. We optimize the best
      cooling configuration and crystal design by compromising the average temperature,
      thermodeformation, and optical phase distortion. The experimental results also
      indicate that a thin sheet of gain medium (1.6 mm thick at 10 at. % doping)
      suffers from a notable bending deformation, which results in an unexpected
      decrease of the output energy.

PMID- 16892126
TI  - Overcoming the impeding effect of core-cladding interface on the progression of
      the second-order nonlinearity in thermally poled optical fibers.
AB  - The spatial distribution of the second-order optical nonlinearity in thermally
      poled optical fibers was characterized with second-harmonic microscopy. The
      second-order optical nonlinearity (SON) was found to be distributed in a layer,
      the progression of which was impeded at the core-cladding interface, which acted
      as an extra potential barrier to the migrating ions. At higher poling voltages
      and temperatures, the SON layer could overcome this barrier and extend further
      into the fiber core. The polarization dependence of the optical nonlinearity
      within the fiber core was also checked and found to be almost negligible.

PMID- 16892127
TI  - Simple optical method for determination of crystal orientation in photorefractive
      crystals.
AB  - A simple optical method for determination of crystallographic orientations +/-x,
      +/-y, and +/-z in photorefractive crystals based on light amplification via
      backward two-wave mixing (TWM) is presented. We consider a photorefractive Fe
      doped lithium niobate crystal (LiNbO(3):Fe) with a standard x-y-z cut as an
      example to illustrate the principle, manipulation, and experimental results of
      this method in detail. Also we see that the direction of the light amplification,
      namely, the direction of the nonreciprocal steady-state energy transfer, strongly
      depends on the direction of the grating vector with respect to the corresponding
      crystallographic axes mainly under the diffusion mechanism. Finally, a way of
      determining the sign of the charge carriers in photorefractive materials is
      proposed.

PMID- 16892128
TI  - Systematic design process for slanted grating couplers.
AB  - We have developed a systematic design process for recently proposed slanted
      grating couplers (SGCs) that operates in the strong coupling regime. Based on
      rigorous analysis of SGC properties, this design process utilizes the k-vector
      diagram and a rigorous grating leaky-mode solver to intentionally enforce the
      phase-match and Bragg conditions. We demonstrate that the resultant SGC designs
      have performance similar to those obtained by parallel micro-genetic algorithm
      (muGA) optimization with the two-dimensional finite-difference time-domain (2D
      FDTD) method. Only two 2D FDTD simulations are necessary in the later stages of
      our systematic design process. Therefore the time saving is tremendous compared
      to a muGA 2D FDTD design tool, which can require thousands of individual 2D FDTD
      simulation runs. We illustrate the utility of our new systematic design process
      with an embedded slanted grating coupler example.

PMID- 16892129
TI  - Tomographic multiaxis-differential optical absorption spectroscopy observations
      of Sun-illuminated targets: a technique providing well-defined absorption paths
      in the boundary layer.
AB  - A novel experimental procedure to measure the near-surface distribution of
      atmospheric trace gases by using passive multiaxis differential absorption
      optical spectroscopy (MAX-DOAS) is proposed. The procedure consists of pointing
      the receiving telescope of the spectrometer to nonreflecting surfaces or to
      bright targets placed at known distances from the measuring device, which are
      illuminated by sunlight. We show that the partial trace gas absorptions between
      the top of the atmosphere and the target can be easily removed from the measured
      total absorption. Thus it is possible to derive the average concentration of
      trace gases such as NO(2), HCHO, SO(2), H(2)O, Glyoxal, BrO, and others along the
      line of sight between the instrument and the target similar to the well-known
      long-path DOAS observations (but with much less expense). If tomographic
      arrangements are used, even two- or three-dimensional trace gas distributions can
      be retrieved. The basic assumptions of the proposed method are confirmed by test
      measurements taken across the city of Heidelberg.

PMID- 16892130
TI  - Unpolarized emissivity with shadow and multiple reflections from random rough
      surfaces with the geometric optics approximation: application to Gaussian sea
      surfaces in the infrared band.
AB  - The emissivity from a stationary random rough surface is derived by taking into
      account the multiple reflections and the shadowing effect. The model is applied
      to the ocean surface. The geometric optics approximation is assumed to be valid,
      which means that the rough surface is modeled as a collection of facets
      reflecting locally the light in the specular direction. In particular, the
      emissivity with zero, single, and double reflections are analytically calculated,
      and each contribution is studied numerically by considering a 1D sea surface
      observed in the near infrared band. The model is also compared with results
      computed from a Monte Carlo ray-tracing method.

PMID- 16892131
TI  - Debye series of normally incident plane-wave scattering by an infinite
      multilayered cylinder.
AB  - We derive the formula of the Debye-series decomposition for normally incident
      plane-wave scattering by an infinite multilayered cylinder. A comparison of the
      scattering diagrams calculated by the Debye series and Mie theory for a graded
      index polymer optical fiber is given and the agreement is found to be satisfied.
      This approach permits us to simulate the rainbow intensity distribution of any
      single order and the interference of several orders, which is of good use to the
      study of the scattering characteristics of an inhomogeneous cylinder and to the
      measurement of the refractive index profile of an inhomogeneous cylinder.

PMID- 16892132
TI  - Dual-LED imaging for finger liveliness detection and its evaluation with
      replicas.
AB  - Unattended fingerprint identification systems need to reject input attempts by a
      replica. Previously, we proposed detecting the color changes of a finger during
      an input action as a signature of liveliness. To improve its reliability, a dual
      LED imaging system is investigated. It employs two LEDs with peak emissions at
      530 and 630 nm to cover the spectral ranges where live fingers show
      characteristic changes. Using nine types of replicas and the live fingers of 42
      participants, we have recorded and analyzed 153 input trials. The two groups of
      data are successfully separated by some defined criteria.

PMID- 16892133
TI  - Time-resolved optical tomography using short-pulse laser for tumor detection.
AB  - Our objective is to perform a comprehensive experimental and numerical analysis
      of the short-pulse laser interaction with a tissue medium with the goal of tumor
      cancer diagnostics. For a short-pulse laser source, the shape of the output
      signal is a function of the optical properties of the medium, and hence the
      scattered temporal optical signal helps in understanding the medium
      characteristics. Initially experiments are performed on tissue phantoms embedded
      with inhomogeneities to optimize the time-resolved optical detection scheme. Both
      the temporal and the spatial profiles of the scattered reflected and transmitted
      optical signals are compared with the numerical modeling results obtained by
      solving the transient radiative transport equation using the discrete ordinates
      technique. Next experiments are performed on in vitro rat tissue samples to
      characterize the interaction of light with skin layers and to validate the time
      varying optical signatures with the numerical model. The numerical modeling
      results and the experimental measurements are in excellent agreement for the
      different parameters studied. The final step is to perform in vivo imaging of
      anesthetized rats with tumor-promoting agents injected inside skin tissues and of
      an anesthetized mouse with mammary tumors to demonstrate the feasibility of the
      technique for detecting tumors in an animal model.

PMID- 16892134
TI  - Hyperspectral confocal microscope.
AB  - We have developed a new, high performance, hyperspectral microscope for
      biological and other applications. For each voxel within a three-dimensional
      specimen, the microscope simultaneously records the emission spectrum from 500 nm
      to 800 nm, with better than 3 nm spectral resolution. The microscope features a
      fully confocal design to ensure high spatial resolution and high quality optical
      sectioning. Optical throughput and detection efficiency are maximized through the
      use of a custom prism spectrometer and a backside thinned electron multiplying
      charge coupled device (EMCCD) array. A custom readout mode and synchronization
      scheme enable 512-point spectra to be recorded at a rate of 8300 spectra per
      second. In addition, the EMCCD readout mode eliminates curvature and keystone
      artifacts that often plague spectral imaging systems. The architecture of the new
      microscope is described in detail, and hyperspectral images from several
      specimens are presented.

PMID- 16892135
TI  - Modeling low-coherence enhanced backscattering using Monte Carlo simulation.
AB  - Constructive interference between coherent waves traveling time-reversed paths in
      a random medium gives rise to the enhancement of light scattering observed in
      directions close to backscattering. This phenomenon is known as enhanced
      backscattering (EBS). According to diffusion theory, the angular width of an EBS
      cone is proportional to the ratio of the wavelength of light lambda to the
      transport mean-free-path length l(s)* of a random medium. In biological media a
      large l(s)* approximately 0.5-2 mm >> lambda results in an extremely small
      (approximately 0.001 degrees ) angular width of the EBS cone, making the
      experimental observation of such narrow peaks difficult. Recently, the
      feasibility of observing EBS under low spatial coherence illumination (spatial
      coherence length Lsc << l(s)*) was demonstrated. Low spatial coherence behaves as
      a spatial filter rejecting longer path lengths and thus resulting in an increase
      of more than 100 times in the angular width of low coherence EBS (LEBS) cones.
      However, a conventional diffusion approximation-based model of EBS has not been
      able to explain such a dramatic increase in LEBS width. We present a photon
      random walk model of LEBS by using Monte Carlo simulation to elucidate the
      mechanism accounting for the unprecedented broadening of the LEBS peaks.
      Typically, the exit angles of the scattered photons are not considered in
      modeling EBS in the diffusion regime. We show that small exit angles are highly
      sensitive to low-order scattering, which is crucial for accurate modeling of
      LEBS. Our results show that the predictions of the model are in excellent
      agreement with the experimental data.

PMID- 16892136
TI  - [Diagnostic values of antibody to citrullinated human fibrinogen in rheumatoid
      arthritis].
AB  - OBJECTIVE: To study the prevalence of antibody to citrullinated human fibrinogen
      (ACF) in rheumatic diseases and the diagnostic values in rheumatoid arthritis.
      METHODS: Human fibrinogen was deiminated by the peptidylarginine deiminase (PAD)
      in the presence of Ca2+ in vitro. ACF was detected by ELISA in 352 patients with
      rheumatic diseases (183 RA, 121 SLE and 48 OA) and 108 healthy controls. The
      sensitivity and specificity in RA were calculated and the correlations between
      ACF and the clinical and laboratory parameters were analysed by SPSS statistical
      software. RESULTS: Compared with SLE (25.62%), OA (18.75%) and healthy control
      (2.78%) respectively, the patients with RA had a significantly higher level of
      ACF (67.21%, P<0.001). ACF had a sensitivity of 67.21% and a specificity of
      84.84% for RA. In the investigated clinical and laboratory parameters of RA, the
      significant correlations were found between ACF and ESR (r=0.386, P<0.001), anti
      CCP antibody (r=0.288, P<0.05) and AKA (r=0.288, P<0.05), respectively.
      Abnormalities in ESR, radiographic progression, IgM-RF, anti-CCP, AKA and APF
      were more often in ACF positive patients than in ACF negative patients. Moreover,
      ACF was positive in 38.00% of IgM-RF negative, 59.81% of AKA negative and 68.22%
      of APF negative patients, respectively. CONCLUSION: ACF is a sensitive and
      specific antibody in diagnosing RA. The ACF test is also very useful in
      diagnosing RA with other autoantibodies negative.

PMID- 16892137
TI  - [Therapeutic effect and impact on cytokine production by methotrexate in
      rheumatoid arthritis].
AB  - OBJECTIVE: To examine the clinical benefit and impact on cytokine production by
      methotrexate in rheumatoid arthritis. METHODS: Thirty patients with RA were
      treated with oral methotrexate (mean, 15 mg per week) as monotherapy for 24
      weeks. Clinical assessment using the American College of Rheumatology (ACR)
      criteria for improvement was performed at baseline and at the end of 2, 4, 8, 12
      and 24 weeks. The pro-inflammation cytokine TNF-alpha, INF-gamma,IL-1beta, IL-6
      and anti-inflammation cytokine IL-10 were measured in RA sera at baseline and
      after 24 weeks of therapy. RESULTS: There was remarkable improvement in disease
      activity following the MTX treatment. At the end of 24 weeks, the percent age of
      ACR20 was 70% (21/30), ACR50 30% (9/30) and ACR70 10% (3/30). The levels of IL-6
      (46.83+/-35.81 vs. 20.92+/-17.98, P=0.001), TNF-alpha (162.52+/-107.63 vs.
      18.32+/-14.36, P=0.026) and INF-gamma (67.79+/-43.76 vs. 35.78+/-27.51, P=0.004)
      were significantly higher than those of the health control at baseline,
      respectively. The levels of TNF-alpha (123.36+/-89.61,P=0.018), INF-gamma
      (41.53+/-13.49, P=0.015), IL-1beta (7.47+/-7.33, P=0.026), IL-6 (26.01+/-25.64,
      P=0.025) were significantly decreased after treatment with methotrexate. In
      contrast, IL-10 was remarkably increased (71.76+/-41.01, P=0.02). CONCLUSION:
      Methotrexate is effective in patients with rheumatoid arthritis. It can suppress
      the symptoms and joint damage. In addition, methotrexate treatment decreases the
      levels of pro-inflammatory cytokine, and increases the level of anti-inflammatory
      cytokine.

PMID- 16892138
TI  - [Effect of multiple amino acid substitutions of collagen II 263-272 on collagen
      induced arthritis].
AB  - OBJECTIVE: To evaluate the effect of multiple amino acid substitutions of C II
      263-272 peptide on collagen-induced arthritis, and explore a therapeutic strategy
      of rheumatoid arthritis. METHODS: A panel of altered C II 263-272 peptides was
      synthesized with substitutions of TCR-contact residues of C II 263-272 with
      alanine. The competitive inhibition of APL to wild type C II 263-272 was analyzed
      by 3H incorporation assay. CIA model was induced by intradermal injection of
      bovine CII. Altered CII peptide was injected subcutaneously in different doses
      (1, 10, 100 microg, respectively, twice per week) after onset of CIA. The
      arthritis index, radiologic and histologic scores were recorded to evaluate the
      severity change of arthritis. Serum levels of IFN-gamma were examined by ELISA.
      RESULTS: Competitive inhibition to wild type C II 263-272 of the altered C II 263
      272 peptides (APL1, APL2, APL3) was found in PBMC from RA patients. Among them,
      APL3 with substitution of residues 267(Q), 270(K) and 271(G) to A showed the most
      significant effect and thus was used in the treatment of CIA rats. We observed
      significantly reduced arthritis scores in CIA rats treated with 100 microg/dose
      of APL as compared with rats treated with PBS and peptide control. The mean
      radiographic and histologic scores was also markedly lower in APL-treated CIA
      rats than in PBS or peptide control-treated rats. On day 35 after immunization,
      the serum level of IFN-gamma in rats was examined and a significantly low level
      of serum IFN-gamma was found in APL-treated rats. CONCLUSION: C II 263-272
      peptide with TCR-contact residues substitutions inhibited joint destruction in
      CIA rats and down-regulated IFN-gamma production, suggesting that altered CII
      peptide might be potentially therapeutic in rheumatoid arthritis.

PMID- 16892139
TI  - [Induction of skin allograft tolerance in mice by using anti-alphabeta T cell
      receptor and anti-CD80 monoclonal antibodies combined with bone marrow
      transfusion].
AB  - OBJECTIVE: To explore the role of anti-alphabeta T cell receptor (TCR) and anti
      CD80 monoclonal antibodies (mAbs) combined with donor bone marrow cells (BMCs)
      infusion in the induction of murine skin allografts tolerance. METHODS: On day 0,
      2 x 10(8) BMCs of BALB/c mice were injected into recipient C57BL/6 mice via the
      tail vein, meanwhile, an intraperitoneal injection of TCRalphabeta mAb (500
      microg) was given. On day 2, CD80 mAb was administered intraperitoneally. Skin
      grafting was performed on day 6. Delayed type hypersensitivity (DTH), mixed
      lymphocyte reaction (MLR), IL-2 reverse assay of MLR, adoptive transfer assay and
      chimerism detection were performed at different time points and tolerance
      mechanisms were investigated. RESULTS: The mean survival time (MST) of BALB/c
      skin allografts in C57BL/6 recipients that were treated by anti-TCRalphabeta and
      anti-CD80 mAbs combined with donor BMCs infusion was 70 days. DTH and MLR assay
      indicated that the tolerant mice displayed significant hyporesponsiveness. The
      result of IL-2 reverse test showed that clone anergy was probably involved in the
      formation of tolerance in the tolerant C57BL/6 mice. In vivo and in vitro
      adoptive transfer assay, suppressive activity in the spleens of tolerant C57BL/6
      mice was observed. Chimerism existed in both the thymus and spleen of the
      tolerant C57BL/6 mice. The chimerism level gradually declined with time.
      CONCLUSION: Treatment of anti-TCRalphabeta and anti-CD80 mAbs combined with donor
      BMCs infusion can successfully induce a long-term tolerance in BALB/c mice to
      C57BL/6 skin graft. Multiple mechanisms, including clone anergy, suppressor cells
      and chimerism are involved in the tolerance.

PMID- 16892140
TI  - [Quantitative study on copy numbers of porcine endogenous retroviruses in genome
      of Banna miniature swine inbred line].
AB  - OBJECTIVE: To investigate the copy numbers of porcine endogenous retroviruses in
      genome of Banna miniature swines for screening of donors in xenotransplantation
      with porcine transplants. METHODS: The genomic DNA of peripheral blood
      mononuclear cells(PBMCs) of 50 Banna miniature swines in 4 inbred sublines and 5
      European Large White Pigs was extracted for the detection to pol, envA, envB,
      envC and envA/C recombinant in PERVs with real-time quantitative/semi
      quantitative PCR and normal PCR. RESULTS: PCR products of pol, envA and envB of
      PERV could be obtained from all the Banna samples, and the mean amount of these
      products was 24.2+/-9.4,13.1+/-8.4,16.4+/-9.8 respectively and was significantly
      different among the inbred herds (P<0.01). The envC and envA/C were not
      amplified. CONCLUSION: The copy numbers of pol, envA and envB genes of PERV in
      porcine genome were significantly different among the inbred herds of Banna
      miniature swines, and envC and envA/C were absent in genome of Banna Miniature
      Swines.

PMID- 16892141
TI  - [Effects of GLP-1 treatment on protection of B cells in Otsuka Long-Evans
      Tokushima fatty rats].
AB  - OBJECTIVE: To investigate the effect of GLP-1 on the blood glucose in type 2
      diabetic rats, and its protective effects on the islet B cells. METHODS: Thirty
      rats were divided into three groups: spontaneous type 2 diabetes animal model
      OLETF rats, GLP-1 [from the twelfth week 56 micro/(kg.d), sc] therapy group and
      LETO rats as control. In the 14th and 20th weeks, standard OGTT including fast
      and 2 h-plasma glucose were measured respectively. In the 14th weeks, 3 rats from
      each group were killed randomly, and the rest of the rats were killed until the
      20th week. Immunostaining with the marker of PCNA, TUNEL, and insulin assessed
      metabolic changes in the islet. Ultrastructure of the B cell was observed with
      the electronic microscope. RESULTS: In the 14th and 20th week, AUC for insulin
      were higher in treated animals (10.86+/-1.56 vs. 9.07+/-1.28, P<0.01) and
      (13.00+/-1.50 vs. 10.35+/-0.86, P<0.01), which was paralleled by a decrease in
      AUC for glucose, (29.93+/-3.15 vs. 34.99+/-4.30, P<0.01) and (38.37+/-3.18 vs.
      42.38+/-2.37, P<0.01). Ex vivo immunostaining with the marker of cell
      proliferation, PCNA, showed that the metabolic changes observed in rats treated
      with GLP-1 were associated with an increase in cell proliferation of the B cell
      (48.9+/-39.6 vs. 39.6+/-9.3, P<0.05). TUNEL staining, a marker of cellular
      apoptosis, indicated a reduction of apoptotic cells within the islet in GLP-1
      treated rats (24.8+/-4.2 vs. 30.8+/-5.8, P<0.01). Immunostaining for the insulin
      showed a significant increase in insulin content in GLP-1-treated animals. GLP-1
      treatment ameliorated the ultrastructure of the B cell. CONCLUSION: Our findings
      have provided evidence that the beneficial effects of GLP-1 in OLETF rats are
      mediated by an increase in islet cell proliferation and a decrease of cellular
      apoptosis.

PMID- 16892142
TI  - [Astragalus and angelica mixture inhibits the renal tubular epithelial cell
      injury induced by aristolochic-acid I].
AB  - OBJECTIVE: To investigate whether Chinese herb astragalus and angelica mixture
      (A&A) have influence on the renal tubular epithelial cell injury induced by
      aristolochic-acid I. METHODS: Human proximal tubular epithelial cell line HK-2
      was pre-treated with AA-I (2.5 mg/L) for 4 hours. Cells were then treated with or
      without A&A for additional 44 hours. Cell apoptosis was evaluated by using FACS.
      Secreted fibronectin (FN) and TGF-beta1 levels were assayed by ELISA. The changes
      of AA-I-induced FN, TGF-beta1 level and the rate of apoptosis were compared
      before and after A&A treatment. RESULTS: There was basement secretion of TGF
      beta1 by HK-2 cells (7.05+/-1.98 microg/L). Both normal serum (N-S) and A&A could
      not induce the cells to secret TGF-beta1(6.35+/-1.99 microg/L and 6.57+/-2.19
      microg/L, vs. control, P>0.05). AA-I could induce the TGF-beta1 secretion by HK-2
      cells (18.26+/-5.98 microg/L, vs. control, P<0.05). A&A could block AA-I-induced
      TGF-beta1 secretion by 63.5% (6.66+/-0.70 microg/L, vs. AA-I, P<0.05). It also
      suppressed AA-I-induced cell apoptosis by 93.7% (3.32%+/-0.41% vs. 19.19%+/-6.32%
      respectively, P<0.001) and FN secretion by 44% (1.64+/-1.11 folds vs. 2.93+/-0.87
      folds respectively, P<0.05). CONCLUSION: A&A inhibits AA-I induced injury in
      human renal proximal tubule epithelial cells, whose mechanism may be partially
      through blocking TGF-beta1 secretion.

PMID- 16892143
TI  - [Effects of peroxisome proliferator-activated receptor-gamma ligand troglitazone
      on colon cancer cell growth].
AB  - OBJECTIVE: To investigate the expression of peroxisome proliferator-activated
      receptor-gamma (PPARgamma) in colon cancer cell lines and the effects of
      PPARgamma activation by its ligand troglitazone on cell growth in SW-480 cells.
      METHODS: PPARgamma expression was detected in Lovo, HT-29 and SW-480 cells using
      western blot. The effects of PPARgamma activation by its ligand troglitazone
      (TGZ) and selective antagonist T0070907 on cell growth were assessed by MTT and
      cell count methods; apoptosis was detected by flow cytometry method. RESULTS:
      Western blot result revealed that PPARgamma protein was highly expressed in Lovo
      and HT-29 cells and there was relatively lower expression in SW-480 cells. Cell
      count method and MTT revealed that activation of SW-480 cells with TGZ resulted
      in inhibition of growth in a dose dependent manner. The effect of anti
      proliferation increased with increasing doses of TGZ. Rates of growth inhibition
      were 3.3%, 8.3%, 25%, and 29% for different doses 5, 10, 20 and 25 micromol/L
      respectively. Flow cytometry method detected apoptosis in a dose-dependent
      manner. When the concentration of TGZ was less than 15 micromol/L , the apoptotic
      effect was found to be weak. The apoptotic effect was prominent when the
      concentration exceeded 20 micromol/L. Cell count method revealed that selective
      antagonist of PPARgamma stimulated cell growth of SW-480 cells in a dose
      dependent manner. CONCLUSION: PPARgamma is expressed in colon cancer cells.
      Activation of PPARgamma by its ligands in colon cells has potent anti
      proliferative and pro-apoptotic effects, suggesting that PPARgamma activation by
      its ligands may provide therapeutic value for colorectal cancer patients.

PMID- 16892144
TI  - [Value of serum procalcitonin in diagnosing bacterial lower respiratory tract
      infections in people with exacerbation of Chronic Obstructive Pulmonary Disease].
AB  - OBJECTIVE: To investigate the changes and clinical implications of serum
      procalcitonin in exacerbation of chronic obstructive pulmonary disease (COPD).
      METHODS: We have evaluated PCT measurement in 45 patients with an exacerbation of
      COPD (group A) and 25 patients with stable COPD (group B), quantitative sputum
      culture was performed, too. PPMs were only regarded as significant if they
      reached a growth of > or =10(7) cfu/mL, indicating the presence of bacterial
      infection. RESULTS: In patients with an exacerbation, 15 patients, sputum yielded
      a high (> or =10(7) cfu/mL) bacterial load (group A1), 30 patients, sputum
      yielded a low (<10(7) cfu/mL) bacterial load or a negative bacterial culture
      (group A2). The levels of procalcitonin in sera from patients of group A1 were
      significantly higher than those from group A2 and group B [0.24 (0.17, 0.28)
      microg/L vs. 0.125 (0.10, 0.18) microg/L vs. 0.12 (0.10, 0.145) microg/L, P=
      0.000, 0.000]. The levels of procalcitonin in sera from patients of group A2 were
      similar to those from group B (P>0.05). Using a cut-off point of 0.155 microg/L
      for PCT, the sensitivities and specificities for bacterial infection in patients
      with an exacerbation of COPD were 93.3% and 60% respectively. CONCLUSION: Serum
      procalcitonin measurements in patients of an exacerbation of chronic obstructive
      pulmonary disease play a role in the diagnosis of bacterial infection.

PMID- 16892145
TI  - [Effects of dexamethasone on acute lung injury in rats induced by
      lipopolysacharide].
AB  - OBJECTIVE: To study the difference between the preventive and therapeutic effects
      of dexamethasone on acute lung injury models induced by lipopolysacharide (LPS)
      in different phases. METHODS: Forty adult male Wistar rats were randomly divided
      into four groups: (1)control group to receive intraperitoneal NS injection (2
      mL/kg). (2)LPS group to receive intraperitoneal LPS injection (5 mg/kg). (3)one
      hour group to receive intraperitoneal dexamethasone injection (2 mg/kg) one hour
      after LPS injection. (4)three-hour group to receive intraperitoneal dexamethasone
      injection (2 mg/kg) three hours after LPS injection. Then histopathology,
      arterial blood gases, lung permeability, wet-to-dry weight ratio and
      immunohistochemistry AQP1 were performed 24 hours later. RESULTS: Dexamethasone
      could improve biological indexes. Lung permeability, wet-to-dry weight ratio and
      immunohistochemistry AQP1 were (5.73+/-1.37), (4.92+/-0.23), (19.92+/-6.47) in
      LPS group, (2.4+/-0.51), (4.89+/-0.21), (33.47+/-9.41) in one-hour group and
      (2.15+/-0.63), (4.57+/-0.14), (40.69+/-9.18) in three-hour group, respectively.
      Dates in three-hour group were prior to those of one-hour group, and there was
      slight but no significant difference between the two groups. CONCLUSION:
      Dexamethasone can improve lung permeability and reduce lung edema. There is no
      need to be treated with glucocorticoids in advance.

PMID- 16892146
TI  - [Changes in hemodynamics and oxygen metabolism of different Child-grade patients
      during orthotopic liver transplantation without veno-venous bypass].
AB  - OBJECTIVE: To investigate the changes in hemodynamics and oxygen metabolism of
      different Child-grade patients during orthotopic liver transplantation (OLT)
      without veno-venous bypass. METHODS: Forty patients with end-stage liver disease
      undergoing non veno-venous OLT under general anesthesia were enrolled in this
      research. Swan-Ganz catheter was placed in the pulmonary artery via right
      internal jugular vein and right radial artery was cannulated to monitor mean
      pulmonary artery pressure (mPAP) and artery blood pressure (ABP) continuously.
      Pulmonary capillary wedge pressure (PCWP) and central venous pressure (CVP) were
      also recorded. Cardiac output (CO) was recorded at several time points, such as,
      30 min after induction (T1), when inferior vena cava and portal vein were clamped
      (T2), 30 min after portal vein was clamped (T3), 10 min after unclamping of
      portal vein (T4), 60 min after graft reperfusion (T5) and at the end of the
      operation (T6). Blood samples were taken from radial and pulmonary artery for
      blood gas analysis and hemodynamic parameters, such as, cardiac index (CI),
      stroke volume index (SVI), pulmonary vascular resistance index (PVRI), and system
      vascular resistance index (SVRI); oxygen delivery (DO2) and oxygen consumption
      (VO2) were also calculated at these time points. RESULTS: (1) The mPAP values
      were much higher in group C than in group A or B at all time points. CVP was
      significantly increased at T1 or T2 in group C as compared with those points of
      Child's B or C. PCWP was increased significantly after unclamping of portal vein
      in all three groups and was much higher at several points in Child's C than in
      Child's A or B. The SVRI value of T1 and the PVRI value of T3 were much lower in
      group C than those points in group A and the value of SVRI/PVRI was less than
      normal except at T3 point. And blood gas analysis elucidated that PaO2 was higher
      than 400 mm Hg at any points. (2) Oxygen consumption was significantly decreased
      during the operation due to less blood supply and was reverted to normal at the
      end point of the operation in all patients. Oxygen delivery was all at least
      1,000 mL/min during OLT and there was no significant difference between different
      groups or different points. CONCLUSION: The hemodynamic state of high cardiac
      output with low peripheral resistance deteriorated when patients' Child-grade
      shifted from A to C. VO2 was less than normal value during OLT until the end
      point.

PMID- 16892147
TI  - [Effects of isoflurane on lung surfactant protein A in rats].
AB  - OBJECTIVE: To examine the effects of different concentrations of Isoflurane on
      the level of surfactant protein A(SP-A) and the expression of SP-A mRNA in the
      lung of rats. METHODS: Thirty-two male Wistar rats were randomly divided into 4
      groups: control group received 40% (volume fraction) O2 inhalation (40% O2, n=8);
      0.7% isoflurane group (n=8), 1.5% isoflurane group (n=8), and 2.0% isoflurane
      group (n=8). They were treated with 40% O2 with 0.7%, 1.5% and 2.0% isoflurane
      respectively. In each group, the rats inhaled experimental gas for 8 hours, and
      then were put to death immediately. Morphological changes of type II pneumocytes
      were observed by transmission electron microscopy. Surfactant protein content in
      broncho-alveolar lavage fluid (BALF) was measured with Western Blotting. The
      level of intracellular SP-A was examined with immunohistochemistry (IHC). To
      assess the relative levels of SP-A mRNA in lung tissue, reverse transcriptase
      polymerase chain reaction (RT-PCR) was used with the co-amplification of the
      "housekeeping" gene GAPDH as internal control. RESULTS: Morphological changes of
      type II pneumocytes were distinct in 1.5% isoflurane and 2.0% isoflurane groups.
      Isoflurane, after three doses, significantly reduced the SP-A content in BALF.
      Control group, 437,112+/-25,654; 0.7% isoflurane group, 355,789+/-28,116; 1.5%
      isoflurane group, 238,554+/-31,531; 2.0% isoflurane group, 223,632+/-25,710
      (P<0.01); Intracellular SP-A content of 1.5% and 2.0% isoflurane groups was less
      than that of the control, whereas 0.7% isoflurane groups did not show any
      significant difference from the control. RT-PCR indicated a reduced expression of
      SP-A mRNA in the lung after 1.5% and 2.0% isoflurane exposure. Control group,
      1.47+/-0.18; 1.5% isoflurane group, 1.19+/-0.13; 2.0% isoflurane group, 1.13+/
      0.12 (P<0.01). CONCLUSION: These findings indicate that 1.5% or more than 1.5%
      isoflurane exposure for eight hours could decrease the expression of the SP-A
      mRNA and synthesis of SP-A in rats, and maybe it could also affect the secretion
      and reuse.

PMID- 16892148
TI  - [Current diagnostic status, clinical and pathologic manifestation for a Crohn's
      disease].
AB  - OBJECTIVE: To evaluate the contemporary diagnostic and therapeutic status for
      Crohn's disease (CD), and analyze its clinical and pathologic manifestation.
      METHODS: Retrospectively we reviewed 220 hospitalized inflammatory bowel disease
      (IBD) cases in which 48 were diagnosed as CD. Data of diagnostic and therapeutic
      details were recorded. RESULTS: In the past 10 years 44 of the 48 CD cases were
      diagnosed in recent and 75.0% of the cases were in the onset age range from 17 to
      40 years. The most common symptoms were abdominal pain, diarrhea and bloody
      stool. 16 (33.3%) of the cases were accompanied with extra-intestinal
      manifestations, 3 (6.3%) with perianal abscess, and 2 (4.2%) with intestinal
      fistulation. The main findings through colonoscopy were ulceration, obstruction
      and cobble stone sign, with a diagnostic correspondence of 85.7% (36/42). Non
      caseous granulomas were totally identified in 43.2% (19/44) of the histology.
      Thirty cases were administrated with Sulfasalazine/Mesalazine (SASP/5-ASA) or
      corticosteroids/immuno-suppressor in which 27 got clinically improved. Thirteen
      patients underwent surgery. CONCLUSION: The diagnostic incidence of Crohn's
      disease has been increased in recent years. The combination of endoscopy,
      radiography and histology is the best way for the diagnosis of CD. Small
      intestinal endoscopy and capsule endoscopy with repeated histopathology and
      follow-up are helpful for the diagnosis.

PMID- 16892149
TI  - [Chloroquine increased radiosensitivity of radioresistant MDA-MB 231 cells and
      its molecular mechanism].
AB  - OBJECTIVE: To study the genes associated with CQ (Chloroquine) increased
      radiosensitivity in radioresistant MDA-MB 231 cells. METHODS: The survival curve
      of MDA-MB 231 breast cancer cells was establish in the presence or absence of CQ
      after irradiation by colongenic assay. The relationship between certain protein
      expressions (MLH1, ERCC1, PARP, RAD51, XRCC4) and CQ increased radiosensitivity
      in radioresistant MDA-MB 231 cells was examined by Western blot method. The genes
      which are associated with CQ increased radiosensitivity were studied by
      microarray analysis. RESULTS: CQ increased deaths of parental MDA-MB 231 cells,
      radiosensitive MDA-MB 231 cells and radioresistant MDA-MB 231 cells were compared
      with those of the CQ-untreated control cells after irradiation, and the Radiation
      Potentiation Factor were 1.21-1.23. The expression of ERCC1 in the presence and
      absence of CQ in the radioresistant cells was significantly higher than that of
      sham-irradiated control cells by Western blot method. After irradiation, RAD51
      level was increased up to 3-hour radiation and then gradually reduced. The
      expression of MLH1 was lower in 24 hours than that of other time points after
      irradiation. There were no differences on the expressions of MLH1, ERCC1, RAD51
      in cells with and without CQ, which suggested that these genes weren't correlated
      with CQ increased radiosensitivity. XRCC4 and PARP levels were not changed by
      irradiation. Microarray analysis showed that TNP3, FRIH, CA21, ADTA genes might
      be related to CQ increased radiosensitivity in radioresistant cells. CONCLUSION:
      CQ can increase radiosensitivity in radioresistant MDA-MB 231 breast cancer
      cells. It is not related to MLH1, ERCC1, PARP, RAD51, XRCC4 genes. TNP3 may play
      an important role in CQ increase radiosensitivity in radioresistant MDA-MB 231
      breast cancer cells.

PMID- 16892150
TI  - [Cloning, identification, and cellular localization of a down-regulated gene
      fragment related with Down Syndrome].
AB  - OBJECTIVE: To clone a novel gene and explore its expression patterns in tissues
      and cells, so as to find its role in the process of encephalopathy in DS.
      METHODS: On the base of our previous microarray's result together with the tissue
      type, we chose EST AI480014 to carry out RACE, then analyzed its expression
      profiles in liver, spleen, kidney, heart, brain by multi-tissues Northern blot,
      after that semi-quantitive RT-PCR was used to reexamine the expression profiles.
      Furthermore, we used ISH to find whether aim gene expressed in neuroglial cells
      cultured in vitro. Finally we performed semi-quantitive RT-PCR to explore whether
      it expressed differently between DS and normal. RESULTS: We gained a 682 bp new
      cDNA fragment (DQ275636) which expressed in all the tissues examined and had no
      alternative splices in them. It expressed highly in brain especially in frontal
      lobe and hippocampus. According to the ISH result we convinced that it expressed
      in neuroglial cells. Using bioinformatics we mapped DQ275636 to chromosome 5q14.
      CONCLUSION: We have obtained a new gene fragment based on the above results.
      According to its expression character and tissue type, it can be suggested that
      this gene has a probable role in the process of encephalopathy in DS.

PMID- 16892151
TI  - [Effect of topical tacrolimus ointment on expression of Toll-like receptors 2 and
      4 in lesional atopic dermatitis skin].
AB  - OBJECTIVE: To investigate the role of Toll-like receptor(TLR) 2 and TLR4 in
      pathogenesis of atopic dermatitis(AD) and the effect of topical tacrolimus
      ointment on expression of TLR2 and TLR4 in lesional AD skin. METHODS:
      Immunohistochemistry was employed to study the expression of TLR2 and TLR4 in
      normal skin and lesional AD skin before and after using topical tacrolimus
      ointment. RESULTS: The basal keratinocytes in normal skin constitutively
      expressed TLR2 and TLR4. In contrast, lesional epidermis from 9 patients with
      acute AD overexpressed TLR2 and TLR4 on the whole epidermis keratinocytes with
      membranous and cytoplasmic staining pattern. After using topical tacrolimus
      ointment for three weeks, TLR2 and TLR4 were expressed on basal and suprabasal
      keratinocytes with membranous and cytoplasmic staining pattern. CONCLUSION: These
      data suggest that TLR2 and TLR4 expressed by epidermal keratinocytes constitute
      part of the innate immune system of the skin, and increased TLR2 and TLR4
      expression may be related to the skin innate immuno-inflammatory response in
      atopic dermatitis. Topical tacrolimus may directly or indirectly inhibit or down
      regulate TLR2 and TLR4 expression in KC and inhibit skin innate immuno
      inflammatory response related to TLR-NFkappaB signal transduction and regulation
      in atopic dermatitis.

PMID- 16892152
TI  - [Analysis of the clinical information of 1,066 cases undergoing prostate magnetic
      resonance examination].
AB  - OBJECTIVE: To evaluate the variation of clinical data and referred purpose of
      prostate magnetic resonance (MR) examination in the past 12 years in Peking
      University First Hospital. METHODS: One thousand and sixty-six patients underwent
      prostate MR examination (1,296 exams) from May 1992 to Sept. 2004. The clinical
      data of the patients were retrospectively analyzed. The number of patients was
      counted and three groups were classified (diagnosing group, staging group and
      follow-up group) according to the purpose of prostate MR examination per year.
      For the diagnosing group, the clinical data of patient's age, symptom, level of
      serum prostate specific antigen (PSA), and the result of ultrasound or digital
      rectal examination (DRE) were evaluated. RESULTS: (1)The number of patients
      increased year by year in the past 12 years, and the majority of the increased
      patients required differential diagnosis. (2) Diagnosing group: the percentage of
      patients with the symptom of BPH increased year by year. The average level of
      serum PSA dropped and the percentage of patients with elevated PSA or with
      nodules detected by ultrasound or DRE referred for detection of prostate cancer
      or with the symptom of metastasis decreased. CONCLUSION: With the widespread
      screening of prostate cancer, more patients of early prostate carcinoma and non
      tumoral lesion in prostate gland are examined by MR imaging.

PMID- 16892153
TI  - [Preparation of chicken egg yolk antibody against Candida albicans and effect of
      temperature on its titer].
AB  - OBJECTIVE: To prepare chicken egg yolk antibody (IgY) against Candida albicans
      and to study its biological properties in the interest of its further
      application. METHODS: Ten 25 weeks old laying hens were immunized with Candida
      albicans. IgY was isolated from the yolks of eggs by the water dilution (WD)
      method. Its yield, purity, and molecular weight were measured by Bradford method
      and Tris-tricine gel electrophoresis, respectively. The antigenicity of IgY was
      determined with Western blot method. The specific combination of IgY and Candida
      albicans was assayed with immunohistochemistry method. The activity of IgY was
      evaluated by enzyme-linked immunosorbent assay (ELISA). RESULTS: The yield and
      purity of IgY were 7.9 g/L and 91.5%, respectively. It had the same molecular
      weight and antigenicity in comparison with IgY of chicken serum and normal
      chicken IgY. It could specifically combine with Candida albicans. Its titer was
      1:12,000. CONCLUSION: The production and purity of IgY were high. Its titer was
      good and did not decrease under a body temperature condition after 48 h. The IgY
      antibody had a combination capacity of specificity for Candida albicans in vitro.

PMID- 16892154
TI  - [Clinical analysis of abnormal uterine bleeding treatment with Thermablate EAS].
AB  - OBJECTIVE: To study the two-year follow-up and contrast research for 182 patients
      by Thermablate EAS Uterine Balloon Therapy (UBT) or Transcervical Resection of
      Endometrium (TCRE). METHODS: We followed up 90 cases of UBT and 92 cases of TCRE
      between Oct. 2003 and June 2005. The mean age of UBT group was 49.4+/-9.4 (34-81)
      years, and that of TCRE group 46.6 +/-8.4 (35-74) years. The mean following-up
      for UBT group was 17.3+/- 5.0 (6-27) months, and that of TCRE group 17.5+/-4.1 (6
      27) months. There was no noticeable difference of the high risk for complication
      between the two groups. The follow up happens twice a year one month after the
      operation. The follow up started in Dec. 2005. RESULTS: The chi(2) value of pain
      during operation between two groups is 12.744. The P value is 0.000. It has
      statistical significance. The pain of UBT group is heavier than TCRE. The chi(2)
      value of blood disappearance between two groups is 24.347. The P value is 0.000.
      It has statistical significance. The duration of the blood disappearance of UBT
      group is shorter than TCRE. The chi(2) value of discharge disappearance between
      two groups is 99.486. The P value is 0.000. It has statistical significance. The
      duration of the blood discharge of UBT group is shorter than TCRE. The chi(2)
      value of blood flow for two years after surgery between two groups is 4.708. The
      P value is 0.03. It has statistical significance. The blood flow of UBT group is
      much more decrease than TCRE. The chi(2) value of dysmenorrheal improved after
      surgery between two groups is 9.970. The P value is 0.002. It has statistical
      significance. The dysmenorrheal improved of UBT group is much better than TCRE.
      CONCLUSION: Thermablate EAS UBT is a new generation of endometrial ablation. Two
      years clinical observation shows that pain can be controlled by oral medicine for
      UBT group. The blood and discharge disappearance of UBT group is shorter than
      TCRE. Two years after the surgery the improvement of blood flow and dysmenorrheal
      released is much better than TCRE. However it probably will take longer time to
      show its long term effectiveness.

PMID- 16892155
TI  - [Study on synthesis and purification of calcium 5-formyltetrahydrofolate].
AB  - OBJECTIVE: To establish a new approach to synthesis and purification of calcium 5
      formytetrahydrofolate. METHODS: Target compound was synthesized by the use of
      folic acid as starting material via reduction, formylation, hydrolysis and salt
      formation RESULTS: The structure of calcium 5-formytetrahydrofolate was confirmed
      by UV, 1H-NMR and elemental analysis and the overall yield was 54%-59%, 14%-17%
      higher than the reported yield. CONCLUSION: A convenient synthetic route was
      developed and it would be suitable for industrial production.

PMID- 16892156
TI  - [Construction of inlay axial surface using B-Spline curve network].
AB  - OBJECTIVE: To realize the requirement of adjacent area accuracy, axial surface
      physical contour and smoothness in the process of inlay computer-aided design
      (CAD). METHODS: A compromised method was brought forward that some assistant 3-D
      constraint lines from occlusion to gingiva were used to lead the inlay contour on
      axial corner and other characterized areas, and two perpendicular 3-D
      constructing lines at adjacent area were used to construct accurate 3-D
      configuration of this area. The axial surface was completely defined by the
      network of specified curves which were two constructing lines and four borders.
      RESULTS: Inlay axial surface was smooth, the contour was consistent with the
      residual tooth body and the 3-D configuration in adjacent area was accurate.
      CONCLUSION: It is feasible to realize the inlay axial surface accuracy,
      smoothness, and consistency using the method of special distributed 3-D B-Spline
      curve network.

PMID- 16892157
TI  - [Identification of human testicular spermatogenic cells at different stages].
AB  - OBJECTIVE: To establish the method to identify human testicular spermatogenic
      cells. METHODS: Cells were dispersed by mechanic disintegration on testicular
      biopsy samples of obstructive azoospermic patients. Diff-Quik staining was
      applied to mixed cell smears. Live cells were observed under inverted microscope
      equipped with Hoffman modulation contrast optics, and classified according to
      their morphology. Chromogenic in situ hybridization (CISH) using chromosome 17
      centromere probe and anti-c-kit immunocytochemistry staining were applied to
      classified cell smears. RESULTS: Sertoli cell, primary pachytene spermatocyte
      (PPS), spermatogonia, round spermatid were the main four round cell groups that
      can be classified under Hoffman optics. In CISH, Sertoli cell, PPS and
      spermatogonia displayed 2 centromere signals, while round spermatid and elongated
      spermatid/sperm displayed 1 centromere signal. In immunocytochemistry staining,
      PPS and spermatogonia displayed positive staining, while Sertoli cell, round
      spermatid and sperm displayed negative staining. CONCLUSION: Dispersed human
      testicular cells displayed different characteristics in live/staining morphology,
      ploidy analysis, cell surface membrane antigen expression. All of these methods
      can be chosen to identify human testicular spermatogenic cells at different
      stages, while cell morphology classifying under Hoffman optics is a simple and
      effective method for live cell identification.

PMID- 16892158
TI  - [Noncoding RNA, a new focus of functional genomic study].
AB  - Approximately 97% of all transcriptional output of the human being is noncoding
      RNA (ncRNA), which has been found to play roles in a great variety of processes,
      and is becoming more and more attractive. This review is a general introduction
      to the concept, classification and functions of ncRNA.

PMID- 16892162
TI  - Cryopreservation of in vitro-grown shoot-tips of tropical taro (Colocasia
      esculenta var. esculenta) by vitrification.
AB  - In vitro shoot-tips of three cultivars of tropical taro (Colocasia esculenta var.
      esculenta (L.) Schott) were successfully cryopreserved by vitrification.
      Different conditioning treatments were required for each of the cultivars, while
      the vitrification protocol was constant for all. For the cultivars E399 and CPUK,
      shoot-tips from three-month-old in vitro plants grown on solidified MS were
      preconditioned on MS with 0.3 M sucrose in the dark for 16 h at 25 degree C. For
      the cultivar TNS, donor plants were preconditioned on solid MS with 90 g per
      liter sucrose for seven weeks before cryopreservation. For vitrification, the
      shoot-tips were loaded with a solution of 2 M glycerol plus 0.4 M sucrose for 20
      min at 25 degree C, dehydrated with PVS2 for 12 min at 25 degree C and plunged in
      liquid nitrogen. Vials were warmed by rapid shaking in a water bath at 40 degree
      C for 1 min 30. Shoot-tips were rehydrated in liquid MS with 1.2 M sucrose for 15
      min at 25 degree C then plated on recovery medium. Shoot-tips resumed growth
      within a week and developed into plantlets six to eight weeks later without any
      callus formation. The best mean recoveries for the three cultivars were 21, 29
      and 30 percent for E399, CPUK and TNS, respectively. This protocol was evaluated
      with five other taro cultivars with no success. However, this study has shown
      that vitrification has potential for cryopreserving tropical taro.

PMID- 16892163
TI  - Cryopreservation of garlic bulbil primordia by the droplet-vitrification
      procedure.
AB  - The droplet-vitrification protocol, a combination of droplet-freezing and
      solution-based vitrification was applied for cryopreserving garlic bulbil
      primordia. The highest survival and regeneration percentages of cryopreserved
      primordia (90.1 to 95.0 percent and 82.7 to 85.0 percent, respectively) were
      achieved after preculture for 2-4 days at 10 degree C on solid medium with 0.1 -
      0.3 M sucrose, loading for 50 minutes in liquid medium with 2 M glycerol + 0.5 M
      sucrose, dehydration with PVS3 vitrification solution for 90-150 min, cooling
      primordia in 5 microl droplets of PVS3 vitrification solution placed on aluminum
      foil strips by dipping these strips in liquid nitrogen, warming them by plunging
      the foil strips into pre-heated (40 degree C) 0.8 M sucrose solution for 30 s and
      further incubation in the same solution for 30 minutes. The optimized droplet
      vitrification protocol was successfully applied to bulbil primordia of five
      garlic varieties originating from various countries and to immature bulbils of
      two vegetatively propagated Allium species, with regeneration percentages ranging
      between 77.4 - 95.4 percent.

PMID- 16892161
TI  - The Role of Social Supports, Spirituality, Religiousness, Life Meaning and
      Affiliation with 12-Step Fellowships in Quality of Life Satisfaction Among
      Individuals in Recovery from Alcohol and Drug Problems.
AB  - Many recovering substance users report quitting drugs because they wanted a
      better life. The road of recovery is the path to a better life but a challenging
      and stressful path for most. There has been little research among recovering
      persons in spite of the numbers involved, and most research has focused on
      substance use outcomes. This study examines stress and quality of life as a
      function of time in recovery, and uses structural equation modeling to test the
      hypothesis that social supports, spirituality, religiousness, life meaning, and
      12-step affiliation buffer stress toward enhanced life satisfaction. Recovering
      persons (N = 353) recruited in New York City were mostly inner-city ethnic
      minority members whose primary substance had been crack or heroin. Longer
      recovery time was significantly associated with lower stress and with higher
      quality of life. Findings supported the study hypothesis; the 'buffer' constructs
      accounted for 22% of the variance in life satisfaction. Implications for research
      and clinical practice are discussed.

PMID- 16892160
TI  - The Genetic Basis of Type 2 Diabetes.
AB  - Type 2 Diabetes results from a complex physiologic process that includes the
      pancreatic beta cells, peripheral glucose uptake in muscle, the secretion of
      multiple cytokines and hormone-like molecules from adipocytes, hepatic glucose
      production, and likely the central nervous system. Consistent with the complex
      web of physiologic defects, the emerging picture of the genetics will involve a
      large number of risk susceptibility genes, each individually with relatively
      small effect (odds ratios below 1.2 in most cases). The challenge for the future
      will include cataloging and confirming the genetic risk factors, and
      understanding how these risk factors interact with each other and with the known
      environmental and lifestyle risk factors that increase the propensity to type 2
      diabetes.

PMID- 16892164
TI  - Cryopreservation of plant germplasm using the encapsulation-dehydration
      technique: review and case study on sugarcane.
AB  - Encapsulation-dehydration is a cryopreservation technique based on the technology
      developed for producing synthetic seeds, i.e. the encapsulation of explants in
      calcium alginate beads. Encapsulated explants are then precultured in liquid
      medium with a high sucrose concentration and partially desiccated before
      freezing. Encapsulating the explants allows the subsequent application of very
      drastic treatments including preculture with high sucrose concentrations and
      desiccation to low moisture contents which would be highly damaging or lethal to
      non-encapsulated samples. An encapsulation-dehydration protocol comprises the
      following steps: pretreatment, encapsulation, preculture, desiccation, freezing
      and storage, thawing and regrowth. Encapsulation-dehydration has been applied to
      around 40 different plant species. The optimization of the successive steps of
      the encapsulation-dehydration protocol is illustrated for sugarcane apices.

PMID- 16892165
TI  - New determinants for tolerance of coffee (Coffea arabica L.) seeds to liquid
      nitrogen exposure.
AB  - The present work establishes for the first time that tolerance of coffee seeds to
      liquid nitrogen (LN) exposure depends on the initial quality of the seedlot and
      on the rewarming regime employed. Seedlot quality was estimated by the parameters
      of a quantal response model of desiccation sensitivity developed previously. The
      percentage of seedlings recovered from cryopreserved seeds was very well
      correlated with the relative humidity (RH) at which 90 percent of the initial
      viability was retained, RH90, as estimated by the model. Whatever the cooling
      regime employed, rewarming the seeds slowly by exposing them to ambient air was
      highly detrimental. Slow rewarming-induced viability loss was not due to
      imbibitional damage since seeds pre-heated at 37 degree C after slow rewarming to
      0 degree C exhibited a survival percentage lower than seeds thawed rapidly to 0
      degree C before sowing. The optimal hydration status for coffee seed
      cryopreservation was also re-examined. Drying seeds in 81 percent RH provided
      survival percentages considerably higher than those obtained using the drying RH
      always employed until now, i.e. 78 percent. A new procedure for slowly precooling
      the seeds prior to immersion in LN was also established. It consisted of placing
      the vials containing the seeds in a dry ice-bath for 25 min. Using this procedure
      in combination with seed drying in 81 percent RH and rapid rewarming in a 37
      degree C water-bath for 30 min ensured the highest survival percentages ever
      obtained with coffee seeds, i.e. 89 percent, a value which was not significantly
      different from the initial viability percentage.

PMID- 16892166
TI  - Cryopreservation of horse semen under laboratory and field conditions using a
      Stirling Cycle freezer.
AB  - A Stirling Cycle freezer has been developed as an alternative to conventional
      liquid nitrogen controlled rate freezers. Horse semen samples were cooled in 0.25
      ml straws and 15 ml bags in the Stirling Cycle freezer under laboratory
      conditions and as a portable device, powered from a car battery. For comparison,
      straws were frozen in a conventional liquid nitrogen controlled rate freezer.
      Upon thawing, motility and viability of samples frozen in the Stirling Cycle
      freezer were not significantly different when compared to samples frozen in the
      liquid nitrogen freezer. Unlike liquid nitrogen systems, the Stirling Cycle
      freezer does not pose a contamination risk, can be used in sterile conditions and
      has no need for a constant supply of cryogen. The freezer has potential for use
      in veterinary and genetic conservation applications.

PMID- 16892167
TI  - The parameter conversion from the Kedem-Katchalsky model into the two-parameter
      model.
AB  - Cryopreservation is an important process for preserving cells and tissues. The
      process itself can, however, cause damage to cells and tissues. During addition
      and removal of a cryoprotective agent (CPA), cells are subjected to imbalanced
      osmotic pressures between the intracellular and extracellular solutions. Cells
      can be injured if these shrinkage and swelling events are beyond their tolerable
      limits. The characteristics of the cell volume changes during these processes
      depend on the types of CPA, the methods of adding and removing of the CPA and the
      permeability of cells to CPA and water. The typical models of this transportation
      are the two-parameter (2-p) model and the Kedem-Katchalsky (K-K) model. The K-K
      model is more general than the 2-p model. However, there is evidence that in many
      cases water and CPAs do not permeate through common pathways, hence the use of
      the reflection coefficient in the K-K model may be unnecessary and in some cases
      it may create conceptual errors. Therefore, the 2-p model is more suitable for
      use as a transport model than the K-K model. The aim of this study is to use the
      values of the K-K model parameters from data in the literature to calculate the
      corresponding parameters for the 2-p model. The results from these simulations
      demonstrate that the cell volume changes during CPA addition and removal from the
      K-K model can be closely estimated by the 2-p model.

PMID- 16892168
TI  - Pathophysiology and treatment of diabetic erectile dysfunction.
AB  - The pathophysiology of diabetes is multifactorial and no single etiology is at
      the forefront. The proposed mechanisms of erectile dysfunction (ED) in diabetic
      patients includes elevated advanced glycation end-products (AGEs) and increased
      levels of oxygen free radicals, impaired nitric oxide (NO) synthesis, increased
      endothelin B receptor binding sites and ultrastructural changes, upregulated
      RhoA/Rho-kinase pathway, NO-dependent selective nitrergic nerve degeneration and
      impaired cyclic guanosine monophosphate (cGMP)-dependent kinase-1 (PKG-1). The
      treatment of diabetic ED is multimodal. Treatment of the underlying hyperglycemia
      and comorbidities is of utmost importance to prevent or halt the progression of
      the disease. The peripherally acting oral phosphodiesterase type 5 (PDE5)
      inhibitors are the mainstay of oral medical treatment of ED in diabetics. Vacuum
      erection devices are an additional treatment as a non-invasive treatment option.
      Local administration of vasoactive medication via urethral suppository or
      intracorporal injection can be effective with minimal side-effects. Patients with
      irreversible damage of the erectile mechanism are candidates for penile
      implantation. Future strategies in the evolution of the treatment of ED are aimed
      at correcting or treating the underlying mechanisms of ED. With an appropriate
      vector, researchers have been able to transfect diabetic animals with agents such
      as neurotrophic factors and nitric oxide synthase (NOS). Further studies in gene
      therapy are needed to fully ascertain its safety and utility in humans.

PMID- 16892169
TI  - Multiple myeloma and B cell lymphoma. Investigation of IL-6, IL-6 receptor
      antagonist (IL-6RA), and GP130 antagonist (GP130A) using various parameters in an
      in vitro model.
AB  - Interleukin-6 (IL-6) affects the survival and proliferation of myeloma cells via
      autocrine and/or paracrine mechanisms. In this study, we investigated the effects
      of IL-6, IL-6 receptor antagonist (IL-6RA), and gp130 antagonist (gp130A) on the
      membrane expressions of IL-6R and gp130, on the viability, on the proliferation,
      on the DNA synthesis, and on the cell cycle phases in several multiple myeloma
      (MM) cell lines and B cell lymphoma cell lines. Our results showed that (1) all
      five MM cell lines (OPM-2, RPMI-8226, U-266, KMS-12-BM, MOLP-8) expressed surface
      IL-6R and gp130, the B cell lymphomas (WSU-1, DOHH-2, U-698) expressed only
      gp130; (2) exogenous IL-6 markedly up-regulated the expression of membrane IL-6R
      (up to 186%) and down-regulated the gp130 receptor (down to 4%) in MM cell lines,
      the membrane expression of gp130 in B cell lymphomas was not altered; (3) IL-6
      markedly increased the spontaneous proliferation (up to 151%) in all MM cell
      lines, that of B cell lymphomas was not affected; (4) IL-6 increased the DNA
      synthesis in the S cell cycle phase of MM cells and arrested the stage G2/M, IL-6
      was ineffective in any cell cycle phase of B cell lymphoma; (5) IL-6RA inhibited
      the membrane IL-6R partially, the proliferation was decreased only slightly; and
      (6) although gp130A inhibited the membrane gp130 completely, the proliferation
      was decreased 81-78% in MM and B cell lymphoma cell lines. This means that gp130
      is not absolutely necessary for the cellular signalling cascade via JAK/STAT and
      RAS/MAPK pathways involved in proliferation and viability. Our results give an
      indication in the therapy of MM: IL-6 antibody (IL-6A) alone or in combination
      with IL-6RA. The latter could be more effective. This kind of therapy is not
      recommended for B cell lymphoma, as these cells have no IL-6R.

PMID- 16892170
TI  - Long-term neuropsychological outcome in preterm twins.
AB  - Few long-term studies have yet described neuropsychological outcome in preterm
      twins. Our aim was to assess, by long-term evaluation, neuropsychological outcome
      in preterm twins in order to define a correct follow-up program. Our study was a
      cohort one, with an index and a comparison group. Neonatal medical records of all
      preterm newborns admitted to our centre between 1991 and 1997 were reviewed and
      selected patients were recalled. The sample population included two matched
      groups of children aged 6-12 years, 86 twins and 86 singletons, submitted to
      paediatric, neurological, psychological, and ophthalmological examinations.
      Inclusion criteria were twin pregnancy and gestational age 27-36 weeks for index
      group; same gestational age, but single pregnancy, for the comparison group. All
      children underwent paediatric and neuropsychiatric examinations, cognitive
      assessment, and psychological evaluation by standardized tests for screening of
      learning specific disorders and language difficulties, and finally,
      ophthalmological examination. In order to study their role in predicting
      neuropsychological outcome, we examined some perinatal prognostic factors by
      statistical analysis. Unfavourable neuropsychological outcome was observed in
      55/172 (32%) children, with different prevalence in the two groups, 42/172 (24%)
      in twins and 13/172 (8%) in singletons. Statistical analysis performed for
      examined prognostic factors showed significant differences in neuropsychological
      outcome with regard only to gestational age < 32 weeks, low birth weight,
      intraventricular haemorrhage, and periventricular leukomalacia. The incidence of
      neuropsychological diseases in the two groups showed significant difference about
      language and learning difficulties. Our data suggest that preterm twins represent
      a particular high-risk category of premature babies, mostly regarding the risk of
      so-called "minimal brain dysfunction", so a careful follow-up is recommended.

PMID- 16892171
TI  - Where do we stand now? Mouse early embryo patterning meeting in Freiburg, Germany
      (2005).
AB  - Mechanism underlying mammalian preimplantation development has long been a
      subject of controversy and the central question has been if any "determinants"
      play a key role in a manner comparable to the non-mammalian "model" system.
      During the last decade, this issue has been revived (Pearson, 2002; Rossant and
      Tam, 2004) by claims that the axes of the mouse blastocyst are anticipated at the
      egg ("prepatterning model"; Gardner, 1997; Gardner, 2001; Piotrowska et al.,
      2001; Piotrowska and Zernicka-Goetz, 2001; Zernicka-Goetz, 2005), suggesting that
      a mechanism comparable to that operating in non-mammals may be at work. However,
      recent studies by other laboratories do not support these claims ("regulative
      model"; Alarcon and Marikawa, 2003; Chroscicka et al., 2004; Hiiragi and Solter,
      2004; Alarcon and Marikawa, 2005; Louvet-Vallee et al., 2005; Motosugi et al.,
      2005) and the issue is currently under hot debate (Vogel, 2005). Deepening our
      knowledge of this issue will not only provide an essential basis for
      understanding mammalian development, but also directly apply to ongoing clinical
      practices such as intracytoplasmic sperm injection (ICSI) and preimplantation
      genetic diagnosis (PGD). These practices were originally supported by a classical
      premise that mammalian preimplantation embryos are highly regulative (Tarkowski,
      1959; Tarkowski, 1961; Tarkowski and Wroblewska, 1967; Rossant, 1976), in keeping
      with the "regulative model". However, if the "prepatterning model" is correct,
      the latter will require critical reassessment.

PMID- 16892172
TI  - Mesodermal anatomies in cnidarian polyps and medusae.
AB  - The cellular and developmental analysis of evolutionary-conserved genes directing
      bilaterian mesodermal and myogenic cell fate previously identified the
      hydromedusan entocodon and its differentiation product, the striated muscle, as
      mesodermal derivatives. In view of these findings we presented a hypothesis
      disputing the diploblast classification of cnidarians without providing further
      explanations for the apparent diploblasty of the polyp stage and the formation of
      the subepidermal striated muscle in those Medusozoa lacking the entocodon nodule
      (Seipel and Schmid, 2005). Hence we carried out a systematic review of the
      histological and experimental evidence for mesodermal differentiations in
      cnidarians. In anthozoan and scyphozoan but not in hydrozoan polyps the
      presumptive mesodermal elements include amoeboid cells, the mesentery retractor
      muscles and scleroblasts, all of which are embedded or deeply rooted in the
      extracellular matrix (mesoglea) and derive from the ectoblastemal cells invading
      the extracellular matrix from the gastrulation site during or shortly after
      endoderm formation. These data lend further support to the cnidarian mesodermate
      hypothesis, whereby cnidarians and bilaterians share a common triploblast
      ancestor, the Urtriploblast, a small, motile, possibly medusa-like organism that
      did not feature a sessile polyp stage in its life cycle. As a consequence the
      diploblasty of the hydrozoan polyps may represent a derived morphology resulting
      from heterochronic modulations of the gastrulation process after endoderm
      formation.

PMID- 16892173
TI  - Genetic interaction between Lef1 and Alx4 is required for early embryonic
      development.
AB  - Lymphoid Enhancer Factor-1 (Lef1) facilitates the assembly of transcriptional
      regulatory complexes and mediates nuclear responses to Wnt signals. We determined
      previously that the mesenchymally restricted, paired-like homeodomain protein
      Aristaless-like 4 (Alx4) interacts with Lef1 and together alters promoter
      activity of candidate genes. In order to define their overlapping functions, mice
      deficient for both Lef1 and Alx4 activity (Lef1-/-/Alx4lstD/lstD) were produced.
      Whereas embryos lacking either Lef1 or Alx4 activity remain viable up to or after
      birth, early embryonic lethality results when both factors were absent. No viable
      Lef1-/-/Alx4lstD/lstD embryos were recovered beyond 9.5 dpc. Between E8.5 and
      E10, viable Lef1-/-/Alx4lstD/lstD embryos were developmentally delayed 0.5 days
      relative to littermates of all other genotypes. Principle among the alterations
      seen in Lef1-/-/Alx4lstD/lstD animals was defective vasculature in both embryonic
      and extra-embryonic tissues. In the yolk sac, while the vascular network is
      present, it were greatly diminished and large vitelline vessels were largely
      absent. Platelet/endothelial cell adhesion molecule (PECAM) staining revealed
      that the major vessels in the head of compound mutant embryos were absent, while
      the other vessels were finer than those seen in normal littermates. Pools of
      blood and pericardial effusion were also apparent in Lef1-/-/Alx4lstD/lstD
      animals, further indicative of a defective vasculature. These data confirm
      genetically the interaction between Lef1 and Alx4 and further reveal unknown,
      overlapping roles for these transcription factors in embryonic vasculogenesis.

PMID- 16892174
TI  - The zic1 gene is an activator of Wnt signaling.
AB  - The zic1 gene plays an important role in early patterning of the Xenopus
      neurectoderm. While Zic1 does not act as a neural inducer, it synergizes with the
      neural inducing factor Noggin to activate expression of posterior neural genes,
      including the midbrain/hindbrain boundary marker engrailed-2. Since the
      Drosophila homologue of zic1, odd-paired (opa), regulates expression of the
      wingless and engrailed genes and since Wnt proteins posteriorize neural tissue in
      Xenopus, we asked whether Xenopus Zic1 acted through the Wnt pathway. Using Wnt
      signaling inhibitors, we demonstrate that an active Wnt pathway is required for
      activation of en-2 expression by zic1. Consistent with this result, Zic1 induces
      expression of several wnt genes, including wnt1, wnt4 and wnt8b. wnt1 gene
      expression activates expression of engrailed in various organisms, including
      Xenopus, as demonstrated here. Together, our data suggest that zic1 is an
      upstream regulator of several wnt genes and that the regulatory relationships
      between opa, wingless and engrailed seen in Drosophila are also present in
      vertebrates.

PMID- 16892175
TI  - Cloning and pattern of expression of the shiro-uo vasa gene during embryogenesis
      and its roles in PGC development.
AB  - The vasa genes are expressed in the germ cell lineage in many organisms, but
      their expression patterns show large variations. Recent studies suggest that vasa
      transcripts are involved in germ cell lineage development. In this paper, we
      isolated the vasa cDNA clone from a teleost, shiro-uo, Leucopsarion petersii and
      examined its expression pattern during embryogenesis. Then, we examined the
      functional significance of vasa mRNA during the formation of primordial germ
      cells (PGCs). The amino acid sequence of shiro-uo VASA is 61.1% identical to that
      of zebrafish. In whole-mount in situ hybridization, vasa transcripts appeared at
      the 4- and 8-cell stages as four spots at both ends of two cleavage planes
      between the lower tier of blastomeres and the yolk cell mass. At the 16-cell
      stage, eight spots were observed. After the blastula stage, shiro-uo vasa
      transcripts showed similar localization as in the zebrafish. Ultrastructural
      analysis of 4-cell stage embryos revealed the presence of a subcellular organelle
      that resembled 'nuage' in the germ cell lineage observed in the embryos of
      various organisms. We carried out micromanipulation of 4- or 8-cell stage embryos
      to remove the vasa mRNA-containing spots and then measured the number of the vasa
      expressing PGCs in the genital ridge of the manipulated embryos. The numbers
      decreased when all of the four spots were removed, indicating that the vasa
      containing spots at early cleavage stages have important functions in the
      development of PGCs.

PMID- 16892176
TI  - Selection of reference genes in mouse embryos and in differentiating human and
      mouse ES cells.
AB  - Embryonic Stem (ES) cells have the potential to form every cell of the body and
      thus are of great promise for tissue transplantation. One of the rising
      techniques that allows studying the differentiation state of ES cells is
      quantitative RT-PCR (qRT-PCR). When relative quantification by qRT-PCR is
      applied, accurate normalization is necessary, since differentiated embryonic stem
      cells and developing embryos contain heterogeneous cell populations. Corrections
      for variations in the qRT-PCR reaction are needed to allow comparisons between
      different samples. We applied the normalization tools geNorm and Normfinder to
      ten reference genes identifying the most stable ones for relative quantification
      of gene expression during differentiation of human ES cells, as well as in
      differentiated mouse ES cells and in the developing mouse embryo. For relative
      quantification by qRT-PCR in these systems, we advise to use normalization
      factors based on multiple stable reference genes. However, when the use of
      several reference genes would be unpractical, a single reference gene in each
      experimental setup could be sufficient. When looking for single stable reference
      genes, beta-actin works best in both mouse embryo and ES cell experiments and
      glyceraldehyde-3-phosphate-dehydrogenase can be applied in both mouse and human
      ES cell experiments.

PMID- 16892177
TI  - Formation of a successional dental lamina in the zebrafish (Danio rerio): support
      for a local control of replacement tooth initiation.
AB  - In order to test whether the formation of a replacement tooth bud in a
      continuously replacing dentition is linked to the functional state of the tooth
      predecessor, I examined the timing of development of replacement teeth with
      respect to their functional predecessors in the pharyngeal dentition of the
      zebrafish. Observations based on serial semithin sections of ten specimens,
      ranging in age from four week old juveniles to adults, indicate that (i) a
      replacement tooth germ develops at the distal end of an epithelial structure,
      called the successional dental lamina, budding off from the crypt epithelium
      surrounding the erupted part of a functional tooth; (ii) there appears to be a
      developmental link between the eruption of a tooth and the formation of a
      successional dental lamina and (iii) there can be a time difference between
      successional lamina formation and initiation of the new tooth germ, i.e., the
      successional dental lamina can remain quiescent for some time. The data suggest
      that the formation of a successional lamina and the differentiation of a
      replacement tooth germ from this lamina, are two distinct phases of a process and
      possibly under a different control. The strong spatio-temporal coincidence of
      eruption of a tooth and development of a successional dental lamina is seen as
      evidence for a local control over tooth replacement.

PMID- 16892178
TI  - Differentiation of human embryonic stem cells into hepatocytes in 2D and 3D
      culture systems in vitro.
AB  - Human embryonic stem cells (hESCs) have enormous potential as a source of cells
      for cell replacement therapies and as a model for early human development. In
      this study we examined the differentiating potential of hESCs into hepatocytes in
      two- and three-dimensional (2D and 3D) culture systems. Embryoid bodies (EBs)
      were inserted into a collagen scaffold 3D culture system or cultured on collagen
      coated dishes and stimulated with exogenous growth factors to induce hepatic
      histogenesis. Immunofluorescence analysis revealed the expression of albumin
      (ALB) and cytokeratin-18 (CK-18). The differentiated cells in 2D and 3D culture
      system displayed several characteristics of hepatocytes, including expression of
      transthyretin, alpha-1-antitrypsin, cytokeratin 8, 18, 19, tryptophan-2,3
      dioxygenase, tyrosine aminotransferase, glucose-6-phosphatase (G6P), cytochrome
      P450 subunits 7a1 and secretion of alpha-fetoprotein (AFP) and ALB and production
      of urea. In 3D culture, ALB and G6P were detected earlier and higher levels of
      urea and AFP were produced, when compared with 2D culture. Electron microscopy of
      differentiated hESCs showed hepatocyte-like ultrastructure, including glycogon
      granules, well-developed Golgi apparatuses, rough and smooth endoplasmic reticuli
      and intercellular canaliculi. The differentiation of hESCs into hepatocyte-like
      cells within 3D collagen scaffolds containing exogenous growth factors, gives
      rise to cells displaying morphological features, gene expression patterns and
      metabolic activities characteristic of hepatocytes and may provide a source of
      differentiated cells for treatment of liver diseases.

PMID- 16892180
TI  - The effect of gender on the pharmacokinetics of verapamil and norverapamil in
      human.
AB  - The effects of gender on the pharmacokinetics of verapamil and its active
      metabolite, norverapamil, following single oral dose (80 mg, Isoptin) to 12
      healthy male (mean age: 25.75+/-2.42 years, mean body weight: 70.59+/-9.94 kg)
      and 12 healthy female subjects (mean age: 24.08+/-2.84 years, mean body weight:
      56.67+/-5.23 kg) were investigated in the present study. Plasma concentrations of
      verapamil and norverapamil were analysed using a modified high-pressure liquid
      chromatography method. Pharmacokinetic parameters were calculated by non
      compartmental analysis for each subject. For verapamil the half-life (t1/2) and
      mean residence time (MRT) were significantly shorter in women than men (p<0.01
      and p<0.05, respectively). For other pharmacokinetic parameters of verapamil
      there were no significant differences between males and females. For
      norverapamil, t1/2, MRT and time to reach to the maximum plasma concentration
      (Tmax) showed statistically significant differences between the two genders. The
      AUC(0-24) and AUC(0-infinity) ratios of norverapamil to verapamil were also
      calculated. The ratios were significantly higher in women compared with men.
      These observations indicate that the elimination rate of verapamil is faster in
      women than men which may be attributed to the higher activity of CYP3A4 or lower
      activity of P-glycoprotein in women compared with men. A contribution of both
      factors in the appearance of gender differences in verapamil pharmacokinetics is
      also possible.

PMID- 16892179
TI  - C/EBPalpha and C/EBPbeta are markers of early liver development.
AB  - Pancreatic cells can be converted to hepatocytes by overexpression of C/EBPbeta
      (Shen, C-N, Slack, J.M.W. and Tosh, D., 2000. Molecular basis of
      transdifferentiation of pancreas to liver. Nature Cell Biology 2: 879-887). This
      suggested that expression of one or more C/EBP factors may distinguish liver and
      pancreas in early development. We have now studied the early expression of
      C/EBPalpha and C/EBPbeta in the mouse embryo and show that both are expressed
      exclusively in the early liver bud and not in the pancreatic buds. Their
      expression is identical to that of hepatocyte nuclear factor 4 (HNF4), another
      key hepatic transcription factor and alpha-fetoprotein (AFP), a differentiation
      product characteristic of immature hepatocytes. Both are complementary to the
      early expression of Pdx1, a key pancreatic transcription factor. These results
      are consistent with the idea that C/EBP factors are master regulators for liver
      development.

PMID- 16892181
TI  - A 'bottom-up' approach for endo-PK/PD analysis.
AB  - A 'bottom-up' PK/PD analysis approach employing system analysis principles of
      convolution/deconvolution and special nonparametric estimation procedures is
      presented to resolve the complex 'endo-PK/PD' of the endogenous form of
      recombinant drugs using erythropoietin (EPO) as an example. A novel cellular
      deconvolution algorithm is presented that facilitates the identification of the
      functional relationship between the variables involved in EPO's complex PK/PD.
      Five sheep each underwent two phlebotomies spaced 4-6 weeks apart when their
      hemoglobin levels were reduced from 12 g/dl to 3-4 g/dl. EPO levels and
      reticulocyte counts were frequently sampled. The data were analysed using end
      constrained cubic splines. The rate of reticulocyte production was determined
      using the novel deconvolution methodology. The erythroid progenitor cells
      activation rate by EPO was estimated from the reticulocyte production rate using
      a lag-time parameter which determines the delay in the reticulocyte appearance in
      the blood relative to the activation of erythroid progenitors. Hysteresis
      minimization combined with cellular deconvolution was employed to determine the
      population PK/PD transduction function relating the progenitor activation rate to
      EPO concentrations in a nonparametric manner without assuming a specific
      structure. The proposed approach provides a rational informative starting point
      for developing parametric PK/PD models to resolve the complex endo-PK/PD of
      recombinant drugs.

PMID- 16892183
TI  - From plasmacytoid to dendritic cell: morphological and functional switches during
      plasmacytoid pre-dendritic cell differentiation.
AB  - Plasmacytoid dendritic cell precursors (pDC/IPC) are the major producers of type
      I interferon and have the unique ability to link innate and adaptive immunity.
      After producing large amounts of type I IFN in response to microbial stimulation,
      they can differentiate into DC capable of stimulating naive T cells and modulate
      the adaptive immune response. In this review, we focus on the transition between
      these two highly specialized cell types, which is accompanied by major
      morphological, structural and functional changes, many of which remain to be
      fully characterized. We propose that the plasmacytoid and dendritic morphologies
      correspond to distinct differentiation states and effector functions.

PMID- 16892182
TI  - Bacteroides fragilis enterotoxin induces cyclooxygenase-2 and fluid secretion in
      intestinal epithelial cells through NF-kappaB activation.
AB  - Bacteroides fragilis produces an approximately 20-kDa heat-labile toxin (B.
      fragilis enterotoxin, BFT) which is known to be associated with diarrhea. To
      determine whether cyclooxygenase (COX)-2, via NF-kappaB activation, can
      contribute to BFT-induced diarrhea, the relationship between COX-2 expression and
      fluid secretion in BFT-stimulated human intestinal epithelial cells was examined.
      BFT stimulation increased the expression of COX-2, but not COX-1, in human
      intestinal epithelial cells. Suppression of the NF-kappaB signal significantly
      decreased COX-2 expression in response to BFT stimulation. Prostaglandin E2
      (PGE2) levels were increased in parallel with COX-2 expression, and, conversely,
      PGE2 production was significantly inhibited when COX-2 or NF-kappaB activities
      were suppressed using COX-2 small interfering RNA (siRNA), p65 NF-kappaB subunit
      siRNA, or a retrovirus encoding the IkappaBalpha superrepressor. In addition, a
      selective COX-2 inhibitor, NS-398, significantly inhibited the increased cAMP
      level induced by BFT stimulation. Furthermore, a selective COX-2 inhibitor
      prevented BFT-induced PGE2 production and ileal fluid secretion in a mouse ileal
      loop model. These results suggest that the secretory response to BFT stimulation
      may be mediated by the production of PGE2, through NF-kappaB activation and the
      up-regulation of COX-2 in intestinal epithelial cells.

PMID- 16892184
TI  - Percent infarct mapping: an R1-map-based CE-MRI method for determining myocardial
      viability distribution.
AB  - Viability detection is crucial for the management of myocardial infarction (MI).
      Signal intensity (SI)-based MRI methods may overestimate infarct size in vivo. In
      contrast to SI, the longitudinal relaxation-rate enhancement (DeltaR1) is an
      intrinsic parameter that is linearly proportional to the concentration of
      contrast agent (CA). Determining DeltaR1 in the presence of an infarct-avid
      persistent CA (PCA) allows determination of the per-voxel percentage of infarcted
      tissue. Introduced here is a DeltaR1-based CE-MRI method, termed percent infarct
      mapping (PIM), for quantifying myocardial viability following delayed PCA
      accumulation. In a canine MI model (N=6), PIMs were generated using a persistent
      CA (PCA) and validated using triphenyltetrazolium-chloride (TTC) histochemistry.
      Voxel-by-voxel R1 maps of the entire left ventricle (LV) were generated 24 and 48
      hr after PCA administration using inversion recovery (IR) with multiple inversion
      times (TIs). PI values were calculated voxel by voxel. Significant correlations
      (P<0.01, R=0.97) were obtained for PI per slice (PIS) determined using PIM vs.
      corresponding TTC-based values. Median deviations of PIS with PIM from that with
      TTC were only 1.01% and -0.53%, at 24 hr and 48 hr. Median deviations from the
      true infarction fraction (IF) were 1.23% and 0.49% of LV at 24 hr and 48 hr,
      respectively. No significant difference was found between PIM24 hr and PIM48 hr.
      DeltaR1-based PIM is an accurate and reproducible method for quantifying
      myocardial viability distribution, and thus enhances the clinical utility of CE
      MRI.

PMID- 16892185
TI  - Proton spectral editing for discrimination of lactate and threonine 1.31 ppm
      resonances in human brain in vivo.
AB  - A single-voxel proton NMR J-difference editing method for discriminating between
      the 1.31 ppm resonances of lactate (Lac) and threonine (Thr) in human brain in
      vivo at 3 T is reported. One double-band and two triple-band Gaussian 180 degrees
      RF pulses, all with a bandwidth of 15 Hz, were employed within an adiabatic
      refocused double-echo localization sequence to induce the target signals of Lac
      and Thr and simultaneously acquire a creatine singlet in each subscan. The
      optimum echo time and the editing efficiency were obtained by numerical analysis
      of the filtering performance. The Lac and Thr signals were extracted, without
      lipid contamination, from three subspectra. Using the calculated yields, the
      concentrations of Lac and Thr in the human occipital cortex were estimated to be
      0.47+/-0.07 and 0.56+/-0.06 mM (mean+/-SD, N=7), respectively, with reference to
      Cr at 8 mM.

PMID- 16892186
TI  - Amide proton transfer imaging of human brain tumors at 3T.
AB  - Amide proton transfer (APT) imaging is a technique in which the nuclear
      magnetization of water-exchangeable amide protons of endogenous mobile proteins
      and peptides in tissue is saturated, resulting in a signal intensity decrease of
      the free water. In this work, the first human APT data were acquired from 10
      patients with brain tumors on a 3T whole-body clinical scanner and compared with
      T1- (T1w) and T2-weighted (T2w), fluid-attenuated inversion recovery (FLAIR), and
      diffusion images (fractional anisotropy (FA) and apparent diffusion coefficient
      (ADC)). The APT-weighted images provided good contrast between tumor and edema.
      The effect of APT was enhanced by an approximate 4% change in the water signal
      intensity in tumor regions compared to edema and normal-appearing white matter
      (NAWM). These preliminary data from patients with brain tumors show that the APT
      is a unique contrast that can provide complementary information to standard
      clinical MRI measures.

PMID- 16892187
TI  - Ischemia-induced modifications in hippocampal CA1 stratum radiatum excitatory
      synapses.
AB  - Relatively mild ischemic episode can initiate a chain of events resulting in
      delayed cell death and significant lesions in the affected brain regions. We
      studied early synaptic modifications after brief ischemia modeled in rats by
      transient vessels' occlusion in vivo or oxygen-glucose deprivation in vitro and
      resulting in delayed death of hippocampal CA1 pyramidal cells. Electron
      microscopic analysis of excitatory spine synapses in CA1 stratum radiatum
      revealed a rapid increase of the postsynaptic density (PSD) thickness and length,
      as well as formation of concave synapses with perforated PSD during the first 24
      h after ischemic episode, followed at the long term by degeneration of 80% of
      synaptic contacts. In presynaptic terminals, ischemia induced a depletion of
      synaptic vesicles and changes in their spatial arrangement: they became more
      distant from active zones and had larger intervesicle spacing compared to
      controls. These rapid structural synaptic changes could be implicated in the
      mechanisms of cell death or adaptive plasticity. Comparison of the in vivo and in
      vitro model systems used in the study demonstrated a general similarity of these
      early morphological changes, confirming the validity of the in vitro model for
      studying synaptic structural plasticity.

PMID- 16892188
TI  - Neonatal caffeine administration causes a permanent increase in the dendritic
      length of prefrontal cortical neurons of rats.
AB  - We studied the morphological changes of the dendritic length of the pyramidal
      neurons of the prefrontal cortex (PFC) induced by the effect of chronic
      administration of caffeine in the neonatal rat. The caffeine (50 mg/kg, s.c.) was
      injected from day 1 after birth (P1) to day 12 (P12). The morphology of the
      pyramidal neurons of layer 3 of the PFC was investigated in these animals at two
      different ages, before puberty (P35) and after puberty (P70). Before the animals
      were sacrificed by using overdoses of sodium pentobarbital and being perfused
      intracardially with 0.9% saline, the locomotor activity in a novel environment
      was measured. The brains were then removed, processed by the Golgi-Cox stain, and
      analyzed by the Sholl method. The dendritic morphology clearly showed that the
      neonatal animals administered caffeine showed an increase in the dendritic length
      of the pyramidal neurons of the PFC when compared with the control animals at
      both ages. The present results suggest that neonatal administration of caffeine
      may in part affect the dendritic morphology of the pyramidal cells of this limbic
      structure and this effect persists after puberty and may be implicated in several
      brain processes.

PMID- 16892190
TI  - Blood attenuation with SSFP-compatible saturation (BASS).
AB  - PURPOSE: To investigate a rapid flow-suppression method for improving the
      contrast-to-noise ratio (CNR) between the vessel wall and the lumen for
      cardiovascular imaging applications. MATERIALS AND METHODS: In this study a new
      dark-blood steady-state free precession (SSFP) sequence utilizing two excitation
      pulses per TR was developed. The first pulse is applied immediately adjacent to
      the slice of interest, while the second is a conventional slice-selective pulse
      designed to excite an SSFP signal for the static spins in the slice of interest.
      The slice-selective pulse is followed by fully refocused gradients along all
      three imaging axes over each TR. The signal amplitude (SA) from the moving spins
      excited by the "saturation" pulse is attenuated since they are not fully
      refocused at the TE. RESULTS: This work provides confirmation, by both simulation
      and experiments, that modest adaptations of the basic True-FISP structure can
      limit unwanted "bright blood" signal within the vessels while simultaneously
      preserving the contrast and speed advantages of this well-established rapid
      imaging method. CONCLUSION: Animal imaging trials confirm that dark-blood
      contrast is achieved with the BASS sequence, which substantially reverses the
      lumen-to-muscle CNR of a conventional True-FISP "bright blood" acquisition from
      14.77 (bright blood) to -13.96 (dark blood) with a modest increase (24.2% of
      regular TR of SSFP for this implementation) in acquisition time to accommodate
      the additional slab-selective excitation pulse and gradient pulses.

PMID- 16892189
TI  - Reduction of reconstruction time for time-resolved spiral 3D contrast-enhanced
      magnetic resonance angiography using parallel computing.
AB  - Time-resolved 3D MRI with high spatial and temporal resolution can be achieved
      using spiral sampling and sliding-window reconstruction. Image reconstruction is
      computationally intensive because of the need for data regridding, a large number
      of temporal phases, and multiple RF receiver coils. Inhomogeneity blurring
      correction for spiral sampling further increases the computational work load by
      an order of magnitude, hindering the clinical utility of spiral trajectories. In
      this work the reconstruction time is reduced by a factor of >40 compared to
      reconstruction using a single processor. This is achieved by using a cluster of
      32 commercial off-the-shelf computers, commodity networking hardware, and readily
      available software. The reconstruction system is demonstrated for time-resolved
      spiral contrast-enhanced (CE) peripheral MR angiography (MRA), and a reduction of
      reconstruction time from 80 min to 1.8 min is achieved.

PMID- 16892191
TI  - In vivo R1-enhancement mapping of canine myocardium using ceMRI with Gd(ABE-DTTA)
      in an acute ischemia-reperfusion model.
AB  - PURPOSE: To demonstrate the usefulness of normalized DeltaR1 (DeltaR1(n)) mapping
      in myocardial tissue following the administration of the contrast agent (CA)
      Gd(ABE-DTTA). MATERIALS AND METHODS: Ischemia-reperfusion experiments were
      carried out in 11 dogs. The method exploited the relatively long tissue lifetime
      of Gd(ABE-DTTA), and thus no fast R1 measurement technique was needed. Myocardial
      perfusion was determined with colored microspheres (MP). RESULTS: With varying
      extent of ischemia, impaired wall motion (WM) and lower DeltaR1(n) values were
      detected in the ischemic sectors, as opposed to the nonischemic sectors where
      normal WM and higher DeltaR1(n) were observed. Based on the DeltaR1(n), data from
      the myocardial perfusion assay and the DeltaR1(n) maps were compared in the
      ischemic sectors. A correlation analysis of these two parameters demonstrated a
      significant correlation (R = 0.694, P < 0.005), validating the DeltaR1(n)-mapping
      method for the quantitation of ischemia. Similarly, pairwise correlations were
      found for the MP, DeltaR1(n), and wall thickening (WT) values in the same areas.
      Based on the correlation between DeltaR1(n) and MP, DeltaR1(n) maps calculated
      with a pixel-by-pixel resolution can be converted to similarly high-resolution
      myocardial perfusion maps. CONCLUSION: These results suggest that the extent of
      the severity of ischemia can be quantitatively represented by DeltaR1(n) maps
      obtained in the presence of our CA.

PMID- 16892192
TI  - Real-time automated tracking and trapping system for sperm.
AB  - We have developed a microscope system for real-time single sperm tracking with an
      automated laser tweezers escape power assay. Phase contrast images of swimming
      sperm are digitized to the computer at video rate. The custom algorithm creates a
      region of interest centered about a sperm in response to a mouse click and
      performs all subsequent tasks autonomously. Microscope stage movement responds to
      feedback from video analysis of swimming sperm to center the sperm with respect
      to the field of view. For escape power assays, sperm are automatically relocated
      to the laser trap focus where they are held for a user-defined duration at fixed
      power, or held as laser power is gradually reduced. The sperm's position is
      automatically monitored to measure the laser power at which the sperm escapes the
      trap. Sperm are tracked for extended durations before and after laser trap
      experiments. Motility measurements including the curvilinear velocity and the
      absolute position of the sperm relative to the cell chamber are calculated and
      written to the hard drive at video rate. Experimental throughput is increased
      over 30 times compared to off-line data analysis. The efficacy of the "track and
      trap" algorithm is validated through examples and comparisons with the manually
      collected data.

PMID- 16892193
TI  - Automatic analysis of aqueous specimens for phytoplankton structure recognition
      and population estimation.
AB  - An automatic microscope image acquisition, evaluation, and recognition system was
      developed for the analysis of Utermohl plankton chambers in terms of taxonomic
      algae recognition. The system called PLASA (Plankton Structure Analysis)
      comprises (1) fully automatic archiving (optical fixation) of aqueous specimens
      as digital bright field and fluorescence images, (2) phytoplankton analysis and
      recognition, and (3) training facilities for new taxa. It enables
      characterization of aqueous specimens by their populations. The system is
      described in detail with emphasis on image analytical aspects. Plankton chambers
      are scanned by sizable grids, divers objective(s), and up to four fluorescence
      spectral bands. Acquisition positions are focused and digitized by a TV camera
      and archived on disk. The image data sets are evaluated by a large set of
      quantitative features. Automatic classifications for a number of organisms are
      developed and embedded in the program. Interactive programs for the design of
      training sets were additionally implemented. A long-term sampling period of 23
      weeks from two ponds at two different locations each was performed to generate a
      reliable data set for training and testing purposes. These data were used to
      present this system's results for phytoplankton structure characterization. PLASA
      represents an automatic system, comprising all steps from specimen processing to
      algae identification up to species level and quantification.

PMID- 16892194
TI  - Cytoskeletal response of microvessel endothelial cells to an applied stress force
      at the submicrometer scale studied by atomic force microscopy.
AB  - Cytoskeleton fibers form an intricate three-dimensional network to provide
      structure and function to microvessel endothelial cells. During accommodation to
      blood flowing, stress fiber bundles become more prominent and align with the
      direction of blood flow. This network either mechanically resists the applied
      shear stress (lateral force) or, if deformed, is dynamically remodeled back to a
      preferred architecture. However, the detailed response of these stress fiber
      bundles to applied lateral force at submicrometer scales are as yet poorly
      understood. In our in vitro study, the tip, topography probe in lateral force
      microscopy of atomic force microscopy, acted as a tool for exerting quantitative
      vertical and lateral force on the filaments of the cytoskeleton. Moreover, the
      authors developed a formula to calculate the value of lateral force exerted on
      every point of the filaments. The results show that cytoskeleton fibers of
      healthy tight junctions in rat cerebral microvessel endothelial cells formed a
      cross-type network, and were reinforced and elongated in the direction of
      scanning under lateral force of 15-42 nN. Under peroxidation (H(2)O(2) of 300
      micromol/L), the cytoskeleton remodeled at intercellular junctions, and changed
      over the meshwork structures into a dense bundle, that redistributed the stress.
      Once mechanical forces were exerted on an area, the cells shrank and lost
      morphologic tight junctions. It would be useful in our understanding of certain
      pathological processes, such as cerebral ischemia/reperfusion injury, which maybe
      caused by biomechanical forces and which are overlooked in current disease
      models.

PMID- 16892195
TI  - Comparative study of the conditions required to image live human epithelial and
      fibroblast cells using atomic force microscopy.
AB  - Successful imaging of living human cells using atomic force microscopy (AFM) is
      influenced by many variables including cell culture conditions, cell morphology,
      surface topography, scan parameters, and cantilever choice. In this study, these
      variables were investigated while imaging two morphologically distinct human cell
      lines, namely LL24 (fibroblasts) and NCI H727 (epithelial) cells. The cell types
      used in this study were found to require different parameter settings to produce
      images showing the greatest detail. In contact mode, optimal loading forces
      ranged between 2-2.8 x 10(-9) and 0.1-0.7 x 10(-9) (N) for LL24 and NCI H727
      cells respectively. In tapping (AC) mode, images of LL24 cells were obtained
      using cantilevers with a spring constant of at least 0.32 N/m, while NCI H727
      cells required a greater spring constant of at least 0.58 N/m. To obtain tapping
      mode images, cantilevers needed to be tuned to resonate at higher frequencies
      than their resonance frequencies to obtain images. For NCI H727 cells, contact
      mode imaging produced the clearest images. For LL24 cells, contact and tapping
      mode AFM produced images of comparable quality. Overall, this study shows that
      cells with different morphologies and surface topography require different
      scanning approaches and optimal conditions must be determined empirically to
      achieve images of high quality.

PMID- 16892196
TI  - Competitive AMPA receptor antagonists.
AB  - Glutamic acid (Glu) is the major excitatory neurotransmitter in the mammalian
      central nervous system (CNS) where it is involved in the physiological regulation
      of different processes. It has been well established that excessive endogenous
      Glu is associated with many acute and chronic neurodegenerative disorders such as
      cerebral ischaemia, epilepsy, amiotrophic lateral sclerosis, Parkinson's, and
      Alzheimer's disease. These data have consequently added great impetus to the
      research in this field. In fact, many Glu receptor antagonists acting at the N
      methyl-D-aspartic acid (NMDA), 2-amino-3-(3-hydroxy-5-methylisoxazol-4
      yl)propionic acid (AMPA), and/or kainic acid (KA) receptors have been developed
      as research tools and potential therapeutic agents. Ligands showing competitive
      antagonistic action at the AMPA type of Glu receptors were first reported in
      1988, and the systemically active 2,3-dihydroxy-6-nitro-7-sulphamoyl
      benzo[f]quinoxaline (NBQX) was first shown to have useful therapeutic effects in
      animal models of neurological disease in 1990. Since then, the quinoxaline
      template has represented the backbone of various competitive AMPA receptor
      antagonists belonging to different classes which had been developed in order to
      increase potency, selectivity and water solubility, but also to prolong the "in
      vivo" action. Compounds that present better pharmacokinetic properties and less
      serious adverse effects with respect to the others previously developed are
      undergoing clinical evaluation. In the near future, the most important clinical
      application for the AMPA receptor antagonists will probably be as neuroprotectant
      in neurodegenerative diseases, such as epilepsy, for the treatment of patients
      not responding to current therapies. The present review reports the history of
      competitive AMPA receptor antagonists from 1988 up to today, providing a
      systematic coverage of both the open and patent literature.

PMID- 16892197
TI  - Model-free parameters from dynamic contrast-enhanced-MRI: sensitivity to EES
      volume fraction and bolus timing.
AB  - PURPOSE: To quantify the unknown relative sensitivities of semiquantitative
      measures from dynamic contrast-enhanced (DCE) MRI to variations in the volume
      fraction V(e) of the extravascular extracellular space (EES), and the duration of
      the contrast injection. MATERIALS AND METHODS: Tissue-uptake curves were
      simulated across various values of F, PS, V(e), and bolus timings, with and
      without additive noise and at different image reacquisition rates. From each, the
      peak of the first derivative (G(peak)), the total uptake after the rapid first
      phase (CE), and the IAUC were calculated and plotted against F for each
      experimental condition. Relationships between each measure and the corresponding
      quantitative measure K(trans) were also examined, particularly for linearity.
      RESULTS: The highest sensitivity to flow was achieved for shorter bolus timings
      for G(peak), CE, and IAUC. G(peak) and IAUC were most linearly related to
      K(trans). The sensitivity to V(e) was lowest for G(peak), followed by IAUC and
      CE. Long sampling intervals resulted in severe underestimation of G(peak), while
      IAUC was unaffected provided that the limits of integration were properly
      applied. G(peak) could not be properly calculated in the presence of noise
      without a prior smoothing of the acquired curves, while IAUC was again unaffected
      by noise. CONCLUSION: G(peak) and IAUC are both useful model-free analogs of
      blood flow (i.e., K(trans)) for pre- and posttreatment comparisons. G(peak) may
      be the better choice in cases where larger changes in V(e) are likely, but only
      if sufficient noise reduction and fast image sampling are applied. If V(e) is
      expected to remain stable, IAUC is superior to G(peak) by virtue of its stability
      in the face of noise and more reliable estimation over a wider range of sampling
      rates.

PMID- 16892198
TI  - EPI image reconstruction with correction of distortion and signal losses.
AB  - PURPOSE: To derive and implement a method for correcting geometric distortions
      and recovering magnetic resonance imaging (MRI) signal losses caused by
      susceptibility-induced magnetic field gradients (SFGs) in regions with large
      static field inhomogeneities in echo-planar imaging (EPI). MATERIALS AND METHODS:
      Factors to account for field inhomogeneities and SFGs were added in a traditional
      EPI equation that was a simple Fourier transform (FT) for expressing the actual k
      space data of an EPI scan. The inverse calculation of this "distorted EPI"
      equation was used as a kernel to correct geometric distortions and reductions in
      intensity during reconstruction. A step-by-step EPI reconstruction method was
      developed to prevent complicated phase unwrapping problems. Some EPI images of
      phantom and human brains were reconstructed from standard EPI k-spaces. RESULTS:
      All images were reconstructed using the proposed multistep method. Geometric
      distortions were corrected and SFG-induced MRI signal losses were recovered.
      CONCLUSION: Results suggest that applying our method for reconstructing EPI
      images to reduce distortions and MRI signal losses is feasible.

PMID- 16892200
TI  - Steady state of echo-shifted sequences with radiofrequency phase cycling.
AB  - Due to a delayed echo-formation, echo-shifted gradient echo sequences (ES-GRE)
      allow for an enhanced T(2)*-weighting at short repetition times. While they are
      in use with and without RF spoiling, analytical solutions are only known for the
      latter. The signal formation in the former could only be assessed in
      approximative form, so far. In this article an exact analytical solution is
      presented for TR-periodic ES-GRE sequences with RF phase cycling. Besides
      providing a better numerical performance, it should be useful for systematic
      sequence development. The relation to recent approximative solutions is
      discussed.

PMID- 16892199
TI  - Modifications of aminoglycoside antibiotics targeting RNA.
AB  - The increased awareness of the central role of RNA has led to realization that
      RNA, as structural and functional information accumulation, is also drug target
      to small molecular therapy. Aminoglycosides are a group of well-known
      antibiotics, which function through binding to specific sites in prokaryotic
      ribosomal RNA (rRNA) and affecting the fidelity of protein synthesis.
      Unfortunately, their clinical practice has been curtailed by toxicity and rapid
      increasing number of resistant strains. Therefore, it is highly desirable to
      design new modified aminoglycosides that will overcome the undesirable properties
      of natural occurring aminoglycosides. On the other hand, aminoglycosides as
      potential antiviral (HIV) agents were also reported. Herein, we survey the
      current efforts to develop new aminoglycoside derivatives with modification and
      reconstruction on each sugar ring and review the latest advances in structure
      activity relationships (SAR).

PMID- 16892201
TI  - Longitudinal assessment of Alzheimer's beta-amyloid plaque development in
      transgenic mice monitored by in vivo magnetic resonance microimaging.
AB  - PURPOSE: To assess the development of beta-amyloid (Abeta) plaques in the brain
      with age in the transgenic mouse model of Alzheimer's disease (AD) pathology by
      in vivo magnetic resonance microimaging (microMRI). MATERIALS AND METHODS: Live
      transgenic mice (Tg2576) and nontransgenic littermates (control) were studied at
      regular intervals between the ages of 12 and 18 months. Plaques were visualized
      using a T(2)-weighted rapid acquisition with relaxation enhancement (RARE)
      sequence. Changes in T(2) relaxation times were followed using a multislice
      multiecho (MSME) sequence. Plaque load and numerical density in MR images were
      calculated using SCIL image software. RESULTS: Abeta plaques were clearly
      detected with the T(2)-weighted RARE sequence in the hippocampal and cortical
      regions of the brain of Tg2576 mice but not in control mice. Following the plaque
      development in the same animals with age showed that plaque area, number, and
      size increased markedly, while T(2) relaxation time showed a decreasing trend
      with age. CONCLUSION: These results demonstrate that microMRI is a viable method
      for following the development of Abeta plaques in vivo, and suggest that this
      method may be feasible for assessing the effect of therapeutic interventions over
      time in the same animals.

PMID- 16892202
TI  - Dobutamine cardiovascular magnetic resonance: a review.
AB  - Dobutamine cardiovascular magnetic resonance (DCMR) is useful for identifying
      myocardial ischemia and viability in patients with known or suspected coronary
      artery disease (CAD). This article reviews the performance and utility of DCMR,
      its association with dobutamine stress echocardiography (DSE), and areas of
      active investigative research.

PMID- 16892203
TI  - Development of a novel optimized breathhold technique for myocardial T2
      measurement in thalassemia.
AB  - PURPOSE: To develop a reproducible fast spin-echo (FSE) technique for accurate
      myocardial T2 measurement with application to iron overload assessment in
      thalassemia. MATERIALS AND METHODS: An FSE sequence was developed to permit
      acquisition of multiple TE images in one breathhold (BH-FSE). A dynamic black
      blood scheme was introduced to better cancel blood signal. A nonselective
      refocusing train was also adopted to suppress stimulated echoes. The optimized
      technique was tested on phantoms and then applied to 10 normal volunteers and 10
      thalassemia patients. Interstudy reproducibility was measured on all the 20
      subjects. RESULTS: The mean difference in T2 values was 1.7% from phantom
      experiments between BH-FSE and the conventional spin-echo (SE) technique. High
      contrast BH-FSE images were acquired from human subjects, with minimal stimulated
      echoes and effective blood suppression (P = 0.0005). The coefficient of variation
      for interstudy reproducibility was 4.3%. T2 values from thalassemia patients were
      substantially lower than those from the normal subjects (45.2 +/- 26.1 msec vs.
      56.9 +/- 8.4 ms, P = 0.02). CONCLUSION: The dynamic black-blood T2 sequence is a
      fast reproducible acquisition that compares favorably with conventional
      techniques, is robust to motion artifacts, and yields high blood-myocardium
      contrast. This technique may provide a useful tool in thalassemia and other
      scenarios requiring myocardial T2 quantification.

PMID- 16892204
TI  - Adaptive bilateral breast MRI using projection reconstruction time-resolved
      imaging of contrast kinetics.
AB  - PURPOSE: To introduce a bilateral implementation of an adaptive imaging technique
      in which both dynamic and high resolution breast MR images are acquired
      simultaneously. MATERIALS AND METHODS: Adaptive three-dimensional bilateral
      breast imaging in the sagittal plane was achieved by combining two elements: a
      projection reconstruction time-resolved imaging of contrast kinetics (PR-TRICKS)
      k-space trajectory and a slab interleaved sequence that imaged alternate breasts
      every TR. A pilot study was performed to evaluate image quality and contrast
      uptake behavior, using eight patients with previously identified benign lesions.
      RESULTS: Adaptive reconstruction demonstrated breast lesions in all eight women
      with similar image quality and signal-to-noise ratio (SNR) to Cartesian images
      with comparable imaging parameters. Contrast enhancement curves covering the
      entire postinjection time period were obtained from the dynamic images and in one
      case compared to previous enhancement profiles from a conventional Cartesian
      trajectory. CONCLUSION: Bilateral dynamic and high spatial resolution images with
      high SNR can be achieved in a clinically feasible manner, providing both kinetic
      and morphologic analysis with a single data set. This may obviate the need for
      multiple MRI examinations for a thorough breast MRI workup.

PMID- 16892205
TI  - Preclinical drug metabolism and pharmacokinetic evaluation of GW844520, a novel
      anti-malarial mitochondrial electron transport inhibitor.
AB  - GW844520 is a potent and selective inhibitor of the cytochrome bc1 complex of
      mitochondrial electron transport in P. falciparum, the parasite primarily
      responsible for the mortality associated with malaria worldwide. GW844520 is
      fully active against the parasite including resistance isolates, showing no cross
      resistance with agents in use. To evaluate full potential of this development
      candidate, we conducted drug metabolism and pharmacokinetic studies of this novel
      anti-malarial. GW844520 had low blood clearance of about 0.5-4% of hepatic blood
      flow and a steady-state volume of distribution of 2-4 times total body water in
      mouse, rat, dog, and monkey. Oral bioavailability was high (51-100%). Consistent
      with the in vivo data, GW844520 had low intrinsic clearance in liver microsomes
      and hepatocytes of animal and human origin, high passive cellular permeability
      and was not a P-glycoprotein substrate. GW844520 did not associate appreciably
      with blood cells but was highly bound to plasma proteins (>99%) in all species.
      GW844520 was a substrate and inhibitor of human CYP2D6 but not of CYP1A2, 2C9,
      2C19, and 3A4. This conjunctive analysis supports continued evaluation of this
      compound in definitive pre-IND studies and exemplifies our strategy supporting
      the discovery of novel agents to treat diseases of the developing world.

PMID- 16892206
TI  - In situ measurement of solvent-mediated phase transformations during dissolution
      testing.
AB  - In this study, solvent-mediated phase transformations of theophylline (TP) and
      nitrofurantoin (NF) were measured in a channel flow intrinsic dissolution test
      system. The test set-up comprised simultaneous measurement of drug concentration
      in the dissolution medium (with UV-Vis spectrophotometry) and measurement of the
      solid-state form of the dissolving solid (in situ with Raman spectroscopy). The
      solid phase transformations were also investigated off-line with scanning
      electron microscopy. TP anhydrate underwent a transformation to TP monohydrate,
      and NF anhydrate (form beta) to NF monohydrate (form II). Transformation of TP
      anhydrate to TP monohydrate resulted in a clear decrease in the dissolution rate,
      while the transformation of NF anhydrate (form beta) to NF monohydrate (form II)
      could not be linked as clearly to changes in the dissolution rate. The
      transformation of TP was an order of magnitude faster than that of NF. The
      presence of a water absorbing excipient, microcrystalline cellulose, was found to
      delay the onset of the transformation of TP anhydrate. Combining the measurement
      of drug concentration in the dissolution medium with the solid phase measurement
      offers a deeper understanding of the solvent-mediated phase transformation
      phenomena during dissolution.

PMID- 16892207
TI  - Kinetic analyses for species differences in P-glycoprotein-mediated drug
      transport.
AB  - P-glycoprotein (P-gp) plays an important role in the pharmacokinetics of drugs.
      There is little information on the species differences in P-gp-mediated drug
      transport activity. The purpose of the present study was to clarify the
      differences in the kinetic parameters and the existence of species differences in
      the P-gp-mediated drug transport activity using seven multidrug resistence1
      (MDR1) transfected cell lines, in which the cDNA was from human, monkey, canine,
      rat (MDR1a and MDR1b), and mouse (mdr1a and mdr1b). The transcellular transport
      of diltiazem, cyclosporin A, and dexamethasone across monolayers of MDR1
      transfected cells. The apparent K(m) values of diltiazem exhibited approximately
      16.5-fold differences among the seven cell lines. Concerning the diltiazem
      transport, the V(max)/K(m) value of human P-gp corrected by the P-gp expression
      level was similar to that of monkey P-gp, but was 5.6-fold higher than that of
      canine P-gp. On the other hand, the corrected V(max)/K(m) value of human P-gp for
      cyclosporin A transport was 3.8-fold higher than that of monkey P-gp. The present
      study would be valuable to evaluate the P-gp function of various animals in the
      same experimental condition. It was clarified that the species differences in P
      gp-mediated drug transport activity evaluated by the corrected V(max)/K(m) value
      differed according to the substrate.

PMID- 16892208
TI  - Degradation rate of lyophilized insulin, exhibiting an apparent Arrhenius
      behavior around glass transition temperature regardless of significant
      contribution of molecular mobility.
AB  - The relative influences of chemical activation energy and molecular mobility in
      determining chemical reactivity were evaluated for insulin lyophilized with
      alpha,beta-poly(N-hydroxyethyl)-L-aspartamide (PHEA), and compared with that for
      insulin lyophilized with trehalose, which had been found to have the ability to
      decrease the molecular mobility of insulin at low humidity. The ratio of the
      observed rate constant k(obs) to the chemical activation energy-controlled rate
      constant k(act) (k(obs)/k(act)) at glass transition temperature (T(g)) was
      estimated to be approximately 0.6 and 0.8 at 6% RH and 12% RH, respectively,
      indicating that the degradation rate is significantly affected by molecular
      mobility at lower humidity conditions. However, these k(obs)/k(act) values at
      T(g) were larger than those for the insulin-trehalose system, and changes in the
      temperature-dependent slope around T(g) were less obvious than those for the
      insulin-trehalose system. Thus, the contribution of molecular mobility to the
      degradation rate in the insulin-PHEA system appeared to be less intense than that
      in the insulin-trehalose system. The subtle change in the temperature-dependent
      slope around T(g) observed in the insulin-PHEA system brought about a significant
      bias in shelf-life estimation when the reaction rate was extrapolated from
      temperatures above T(g) according to the Arrhenius equation.

PMID- 16892209
TI  - Influence of different polymers on the crystallization tendency of molecularly
      dispersed amorphous felodipine.
AB  - The ability of various polymers to inhibit the crystallization of amorphous
      felodipine was studied in amorphous molecular dispersions. Spin-coated films of
      felodipine with poly(vinylpyrrolidone) (PVP), hydroxypropylmethylcellulose
      acetate succinate (HPMCAS), and hydroxypropylmethylcellulose (HPMC) were prepared
      and used for measurement of the nucleation rate and to probe drug-polymer
      intermolecular interactions. Bulk solid dispersions were prepared by a solvent
      evaporation method and characterized using thermal analysis. It was found that
      each polymer was able to significantly decrease the nucleation rate of amorphous
      felodipine even at low concentrations (3-25% w/w). Each polymer was found to
      affect the nucleation rate to a similar extent at an equivalent weight fraction.
      For HPMC and HPMCAS, thermal analysis indicated that the glass transition
      temperature (T(g)) of the solid dispersions were not significantly different from
      that of felodipine alone, whereas an increase in T(g) was observed for the PVP
      containing solid dispersions. Infrared spectroscopic studies indicated that
      hydrogen bonding interactions were formed between felodipine and each of the
      polymers. These interactions were stronger between felodipine and PVP than for
      the other polymers. It was speculated that, at the concentrations employed, the
      polymers reduce the nucleation rate through increasing the kinetic barrier to
      nucleation.

PMID- 16892210
TI  - Influence of solid phase and formulation processing on stability of Abbott-232
      tablet formulations.
AB  - Abbott-232 is a chemically stable, highly water soluble non-hygroscopic compound
      selected for development as a potent uroselective alpha(1A) agonist. An
      anhydrate, a monohydrate, and an amorphous phase were isolated. The anhydrate was
      chosen for formulation development based on solid-state characterization.
      Excipients for immediate release (IR) tablet formulations were selected according
      to compatibility studies. However, the prototype IR tablets designed for clinical
      trials were found to be chemically unstable. Thus, process-induced phase
      transformation was investigated as the likely cause of the observed instability.
      Since the drug loading in the formulations was low (1%), model granulations
      containing 30% drug were evaluated to test this hypothesis. Investigation using a
      variety of analytical techniques indicated that the observed degradation was,
      indeed, a result of a solution-mediated phase transformation from anhydrate to
      amorphous Abbott-232 during wet granulation. A new direct compression formulation
      was, therefore, developed to prevent the solution-mediated process induced phase
      transition. Since the drug loading was low, a polarized light microscope (PLM)
      method was used to evaluate the solid phase in the new formulation. PLM confirmed
      that the original anhydrate form remained unchanged in tablets manufactured by
      the dry process. Stability studies confirmed that both IR and extended release
      (ER) tablets of Abbott-232 were successfully developed for clinical trials using
      direct compression.

PMID- 16892212
TI  - Crystal structure of carnidazole form II from synchrotron X-ray powder
      diffraction: structural comparison with form I, the hydrated form and the low
      energy conformations in vacuo.
AB  - The crystal structure of carnidazole form II, O-methyl [2-(2-methyl-5-nitro-1H
      imidazole-1-yl)ethyl]thiocarbamate, has been determined using synchrotron X-ray
      powder diffraction in combination with simulated annealing and whole profile
      pattern matching, and refined by the Rietveld method. For structure solution, 12
      degrees of freedom were defined: one motion group and six torsions. Form II
      crystallizes in space group P2(1)/n, Z=4, with unit cell parameters after
      Rietveld refinement: a=13.915(4), b=8.095(2), c=10.649(3) A, beta=110.83(1)
      degrees, and V=1121.1(5) A3. The two polymorphic forms, as well as the hydrate,
      crystallize in the monoclinic space group P2(1)/n having four molecules in the
      cell. In form II, the molecules are held together by forming two infinite zig-zag
      chains via hydrogen bonds of the type N--H...N, the same pattern as in form I. A
      conformational study of carnidazole, at semiempirical PM3 level, was performed
      using stochastic approaches based on modification of the flexible torsion angles.
      The values of the torsion angles for the molecules of the two polymorphic forms
      and the hydrate of carnidazole are compared to those obtained from the
      conformational search. Form I and form II are enantiotropic polymorphic pairs
      this agrees with the fact that the two forms are conformational polymorphs.

PMID- 16892211
TI  - Characterization of temperature-induced phase transitions in five polymorphic
      forms of sulfathiazole by terahertz pulsed spectroscopy and differential scanning
      calorimetry.
AB  - The far-infrared properties of all five known polymorphic forms of the drug
      sulfathiazole have been studied by terahertz pulsed spectroscopy and low
      frequency Raman spectroscopy. The observed spectra of the different polymorphs
      are distinctly different. Terahertz pulsed spectroscopy proves to be a rapid and
      complementary alternative to other physical characterization techniques reported
      in the literature for distinguishing between the five forms. Variable-temperature
      measurements (293-473 K) of all polymorphic forms have been performed. The phase
      transitions observed have been related to thermal analysis data. Form I is the
      form stable at high temperature of sulfathiazole with a melting point of about
      475 K. Form II melts at around 470 K and recrystallizes at higher temperatures to
      form I. Forms III, IV, and V all convert to form I via a solid-solid phase
      transition at temperatures below 450 K. The phase transitions can be monitored by
      terahertz pulsed spectroscopy. Polymorphic impurities of the samples can be
      detected in the room temperature spectra and their effect on the phase transition
      behavior can be studied.

PMID- 16892219
TI  - Alois Jungbauer: protein bioengineering.

PMID- 16892220
TI  - Carl J. Douglas: gene expression in plants.

PMID- 16892221
TI  - Giorgio Carta: bioseparations.

PMID- 16892222
TI  - Henry Daniell: chloroplast genetic engineering.

PMID- 16892223
TI  - The social, moral, ethical, legal and political implications of today's
      biological technologies: an Indian point of view.
AB  - The last 50 years have seen an increasing emphasis on ethical, moral, social,
      legal, political and economic implications of science for reasons that are
      discussed in this article. Biotechnology has been no exception to this trend.
      Areas of biotechnology where the above implications have been important, are
      briefly described. Ethical and related issues in today's biology-based
      technologies are discussed with special reference to India. Examples of
      technological exploitation within a country, or of one country by another, using
      modern biology-based technologies are given. The possible implications of one new
      and emerging biology-based technology are discussed. It is concluded that a well
      informed and knowledgeable society is the only assured insurance against possible
      misuse of biology-based technologies of today and tomorrow, including their use
      for the exploitation of people. The recent decision of the Prime Minister of
      India to set up a National Knowledge Commission is mentioned in this context.

PMID- 16892224
TI  - Macromolecular immunosuppressants.
AB  - Recombinant immunosuppressants have come of age and represent a significant class
      of quite diverse drugs. They target extracellular molecules, and either label or
      inhibit them. Those targets are soluble factors or membrane proteins almost all
      of which are components of a very complex molecular network of communication and
      amplification. Notably, many recombinant immunosuppressants have been developed
      in a rather short period of time. This is due to the fact that developing the
      actual drug is left to nature, so to speak; either it is a human protein as is
      the case for Anakinra or it is an antibody or antibody derivative "developed" by
      the immune system of mice or rats following exposure to the antigen. The
      challenge for developing recombinant immunosuppressants is to identify relevant
      targets. It is no longer very difficult to generate proteins to targets, once
      those are identified. The clinical use of recombinant immunosuppressants has yet
      to show which targets are truly relevant and which drugs prove effective.

PMID- 16892225
TI  - Using budding yeast to screen for anti-prion drugs.
AB  - Prions are misfolded proteins capable of propagating their altered conformation
      which are commonly considered as the causative agent of transmissible spongiform
      encephalopathies, a class of fatal neurodegenerative diseases. Currently, no
      treatment for prion-based diseases is available. Recently we have developed a
      rapid, yeast-based, two-step assay to screen for anti-prion drugs [1]. This new
      method allowed us to identify several compounds that are effective in vivo
      against budding yeast [PSI+] and [URE3] prions but also able to promote mammalian
      prion clearance in three different cell culture-based assays. Taken together,
      these results validate our method as an economic and efficient high-throughput
      screening approach to identify novel prion inhibitors or to carry on
      comprehensive structure-activity studies for already isolated anti-mammalian
      prion drugs. These results suggest furthermore that biochemical pathways
      controlling prion formation and/or maintenance are conserved from yeast to human
      and thus amenable to pharmacological and genetic analysis. Finally, it would be
      very interesting to test active drugs isolated using the yeast-based assay in
      models for other diseases (neurodegenerative or not) involving amyloid fibers
      like Huntington's, Parkinson's or Alzheimer's diseases.

PMID- 16892226
TI  - Engineering the acetyl-CoA transportation system of candida tropicalis enhances
      the production of dicarboxylic acid.
AB  - Dicarboxylic acids (DCAs) can be obtained by oxidizing alkanes by Candida
      tropicalis. Through alpha-monocarboxylic acids (MCAs), alpha- and omega-oxidation
      yield alpha- or omega-DCAs, respectively. However, both MCAs and DCAs may be
      degraded to acetyl-CoA by beta-oxidation, resulting in a limited DCA yield.
      Acetyl-CoA can be transported into the mitochondrion for the TCA cycle by
      carnitine acetyltransferase (CAT), by which the energy generation and beta
      oxidation are connected. In this paper, we present a method to reconstruct the
      metabolic pathway by inhibiting the acetyl-CoA transportation system. Metabolic
      engineering is applied on the acetyl-CoA transportation system, but not the key
      enzymes in beta-oxidation. Starting with the original strain W10-1, cat
      heterozygote CZ-15 and cat homozygote CKC-11 were obtained by gene knockout. The
      CAT specific activity in CZ-15 was about 50% lower than that in W10-1, resulting
      in a 21.0% increase of the DCA concentration, and a 12% increase of the molar
      conversion of alkane, reaching 61.6%. However, no CAT activity was detected in
      CKC-11, and CKC-11 could not grow on alkane. These results indicate that
      inhibition of beta-oxidation via reconstruction of the transportation process
      between organelles can facilitate DCA production, but that totally blocking the &
      betagr;-oxidation would be harmful for energy supply. We thus provide a novel
      insight into regulation of the beta-oxidation system and metabolic flux. Further
      understanding of beta-oxidation and the acetyl-CoA transportation system in
      Candida tropicalis is reached through examination of fermentation data by
      metabolic flux analysis.

PMID- 16892227
TI  - Properties of immobilized pepsin on Modified PMMA microspheres.
AB  - In this work we use micro-size poly(methyl methacrylate)/acrylaldehyde
      microspheres as a support for pepsin immobilization. The aldehyde groups on the
      microspheres offer a very simple, mild and firm combination for enzyme
      immobilization. The amount of enzyme we can bind to this support reaches 82 mg/g,
      which is much higher than for other supports (mostly less than 10 mg/g). Compared
      to free enzyme, the Km of immobilized enzyme is increased, whereas the Vmax is
      decreased. Further, the Vmax/Km value for immobilized pepsin is about 50% of the
      value for free enzyme. This is better than values reported previously, generally
      lower than 35%. The optimum temperature shifts from 43 degrees C for free pepsin
      to 47 degrees C. However, the optimum pH does not change between free and
      immobilized enzyme. This improved resistance of the immobilized enzyme towards
      changes in temperature and pH also shows that the aldehyde modified poly(methyl
      methacrylate)/acrylaldehyde microspheres can be a valuable support for pepsin
      immobilization.

PMID- 16892228
TI  - Enantioselective reduction of acetophenone and its derivatives with a new yeast
      isolate Candida tropicalis PBR-2 MTCC 5158.
AB  - The enantioselective bioreduction of acetophenone and its various analogues has
      been carried out using a new yeast strain, Candida tropicalis MTCC 5158, to
      obtain the corresponding (S)-aryl ethanols with good yield and almost absolute
      enantioselectivity. The catalytic ability of this microbial strain for
      acetophenone reduction has been examined and also various parameters of the
      bioreduction reaction have been optimized. Studies on the catalytic performance
      showed that this microorganism is capable of carrying out the reduction in a
      broad range of pH (3-10) and temperature (25-40 degrees C), making it a more
      versatile biocatalyst. The preparative scale bioreduction of acetophenone using
      resting cells of Candida tropicalis yielded S-(-)-1-phenyl ethanol with 43% yield
      and >99% enantiomeric excess.

PMID- 16892229
TI  - Electric field driven jetting: an emerging approach for processing living cells.
AB  - This paper reports for the first time the ability to process living cellular
      materials by means of electrified jets at electric field strengths of up to 2
      kV/mm. Bio-suspensions containing living human Jurkat cells at different
      concentrations were processed via this jetting approach. The jetting process was
      carried out at an electric field strength between 0.67 kV/mm and 2 kV/mm,
      corresponding to an applied voltage of 10-30 kV between two electrodes
      approximately 15 mm apart. The Jurkat cells were jetted under sterile conditions,
      collected in petri dishes and incubated for 24 and 48 hours. During and after
      incubation, cells were assessed for survival and structural damage; cells were
      found to be unharmed and to retain their integrity under all electric field
      strengths examined. At all field strengths jetting took place in the unstable
      mode. Good correlation was observed between droplet distribution plots generated
      by way of laser spectroscopy and estimated values from measurements of droplet
      relics.

PMID- 16892230
TI  - The first automated synthesis of ferrocene-labelled phosphorothioate DNA probe: a
      new potential tool for the fabrication of DNA microarrays.
AB  - We report the synthesis and the characterisation of the first electroactive
      ferrocene-labelled oligonucleotide phosphorothioate (ODN-Fc-Ps) probe obtained by
      automated synthesis. The grafting of ODN-Fc-Ps probe on gold electrode resulted
      in the appearance of the ferrocene redox couple in cyclic voltammetry confirming
      the effectiveness of the ODN grafting. The electrochemical response of the
      modified electrode was analysed in aqueous media before and after hybridisation
      with ODN target. The hybridisation with ODN target induces a large conformational
      change in the surface-confined DNA structure monitored by cyclic voltammetry of
      the ferrocene marker which confirms the potential of ferrocene-labelled
      oligonucleotide phosphorothioate to develop electrochemical DNA chips.

PMID- 16892235
TI  - The art of bioprocessing.

PMID- 16892241
TI  - Meeting report: Public health in reverse?

PMID- 16892236
TI  - About the cover: The Z basic protein tag.

PMID- 16892242
TI  - Our senior editors. Gerhard Eisenbrand: food chemistry and environmental
      toxicology.

PMID- 16892243
TI  - Our senior editors. Stefan Buchholz: industrial biotechnology.

PMID- 16892244
TI  - Cancer immunotherapy.
AB  - Cancer is the second leading cause of death in the industrialized world. Most
      cancer patients are treated by a combination of surgery, radiation and/or
      chemotherapy. Whereas the primary tumor can, in most cases, be efficiently
      treated by a combination of these standard therapies, preventing the metastatic
      spread of the disease through disseminated tumor cells is often not effective.
      The eradication of disseminated tumor cells present in the blood circulation and
      micro-metastases in distant organs therefore represents another promising
      approach in cancer immunotherapy. Main strategies of cancer immunotherapy aim at
      exploiting the therapeutic potential of tumor-specific antibodies and cellular
      immune effector mechanisms. Whereas passive antibody therapy relies on the
      repeated application of large quantities of tumor antigen-specific antibodies,
      active immunotherapy aims at the generation of a tumor-specific immune response
      combining both humoral and cytotoxic T cell effector mechanisms by the host's
      immune system following vaccination. In the first part of this review, concurrent
      developments in active and passive cancer immunotherapy are discussed. In the
      second part, the various approaches for the production of optimized monoclonal
      antibodies used for anti-cancer vaccination are summarized.

PMID- 16892245
TI  - Purification of intravenous immunoglobulin G from human plasma--aspects of yield
      and virus safety.
AB  - Plasma-derived intravenous immunoglobulin (IVIG) preparations have been
      successfully applied for the prophylactic prevention of infectious diseases in
      immunodeficient patients. In addition to its replacement therapy of primary and
      secondary antibody deficiencies, IVIG has found increased use in autoimmune and
      inflammatory diseases. IVIG has become the major plasma product on the global
      blood product market. The world wide consumption nearly tripled between 1992 and
      2003, from 19.4 to 52.6 tons. Classical manufacturing processes of IVIG, but also
      new strategies for purification are discussed with respect to practicability and
      yield. Ethanol fractionation is still the basis for most IVIG processes, although
      isolation and purification of immunoglobulin G (IgG) by chromatography has gained
      ground. The efficiency of virus inactivation methods and virus removal techniques
      in terms of logarithmic reduction factors are analyzed, but also the IgG losses
      are taken into consideration. Some of these methods also have the ability to
      separate prions. High pathogen safety and high yields have become the dominant
      goals of the plasma fractionation industry.

PMID- 16892246
TI  - Manufacturing of recombinant therapeutic proteins in microbial systems.
AB  - Recombinant therapeutic proteins have gained enormous importance for clinical
      applications. The first recombinant products have been produced in E. coli more
      than 20 years ago. Although with the advent of antibody-based therapeutics
      mammalian expression systems have experienced a major boost, microbial expression
      systems continue to be widely used in industry. Their intrinsic advantages, such
      as rapid growth, high yields and ease of manipulation, make them the premier
      choice for expression of non-glycosylated peptides and proteins. Innovative
      product classes such as antibody fragments or alternative binding molecules will
      further expand the use of microbial systems. Even more, novel, engineered
      production hosts and integrated technology platforms hold enormous potential for
      future applications. This review summarizes current applications and trends for
      development, production and analytical characterization of recombinant
      therapeutic proteins in microbial systems.

PMID- 16892247
TI  - Single-step recovery and solid-phase refolding of inclusion body proteins using a
      polycationic purification tag.
AB  - A strategy for purification of inclusion body-forming proteins is described, in
      which the positively charged domain Z(basic) is used as a fusion partner for
      capture of denatured proteins on a cation exchange column. It is shown that the
      purification tag is selective under denaturing conditions. Furthermore, the new
      strategy for purification of proteins from inclusion bodies is compared with the
      commonly used method for purification of His(6)-tagged inclusion body proteins.
      Finally, the simple and effective means of target protein capture provided by the
      Z(basic) tag is further successfully explored for solid-phase refolding. This
      procedure has the inherited advantage of combining purification and refolding in
      one step and offers the advantage of eluting the concentrated product in a
      suitable buffer.

PMID- 16892248
TI  - Rapid and selective isolation of beta-xylosidase through an activity-based
      chemical approach.
AB  - beta-Xylosidase is a key enzyme in the xylanolytic system with a great potential
      in many biotechnological applications, especially in the food as well as the pulp
      and paper industries. We have developed a chemical approach for the rapid
      screening and isolation of beta-xylosidase. Activity probe LCL-6X targeting beta
      xylosidase was utilized in this study. It carries a beta-xylopyranosyl
      recognition head, a latent trapping device consisting of a 2-fluoromethylphenoxyl
      group, and a biotin reporter group. The biotin reporter group serves both as a
      readout device and as a tool for enriching the labeled proteins. LCL-6X could
      selectively label a model beta-xylosidase from Trichoderma koningii. All other
      bystander proteins used in this study, including phosphorylase b, BSA, ovalbumin,
      carbonic anhydrase, and trypsin inhibitor, gave negligible cross-labeling effect.
      With the assistance of streptavidin agarose beads and mass spectrophotometry for
      the recovery and identification of the biotinylated proteins, we demonstrated
      that LCL-6X could be successfully applied to identify a bi-functional enzyme with
      alpha-L-arabinofuranosidase/beta-xylosidase activity from the total protein
      extract of a Pichia expressing system and a prospective beta-xylosidase in the
      culture medium of Aspergillus fumigatus. The beta-xylosidase activities from
      numerous microbes were also screened using the LCL-6X probe. Preliminary results
      showed significant differences among these microbial sources and some distinct
      protein bands were observed. Thus, we have successfully developed a novel
      chemical probe that has potential applications in xylan-related research.

PMID- 16892250
TI  - Separation of catechin compounds from different teas.
AB  - Catechin compounds from Korean and Chinese green tea, and pu-erh, Indian black,
      Longjing, Tieguanyin, Bamboo, Jasmine, Oolong, Flower, Red teas, as potential
      anticancer and antioxidant components, were target material in this work. After
      extracting the green tea with water at 50 degrees C for 4 h, the extract was
      partitioned with water/chloroform, which was best suited to remove caffeine
      impurity from the extract. Further, the resulting extract was partitioned with
      water/ethyl acetate to deeply purify the five catechin compounds
      epigallocatechin, (+) catechin, epicatechin, epigallocatechin gallate and
      epicatechin gallate. The extracted samples were analyzed by reversed-phase high
      performance liquid chromatography. The mobile phase applied was the binary system
      of A (water/acetic acid, 100/0.1 vol%) and B (acetonitrile/acetic acid 100/0.1
      vol%) from 90:10 to 70:30 (A:B vol%) in a linear gradient over 30 min time. The
      amount of catechin compounds extracted from Chinese green tea was 114.65% higher
      than from the Korean green tea. Comparing various tea sorts, the green teas
      contained more than 1.7 times of the five catechin compounds contained in other
      teas.

PMID- 16892249
TI  - Effect of Vitreoscilla hemoglobin on production of a chemotherapeutic enzyme, L
      asparaginase, by Pseudomonas aeruginosa.
AB  - The production of L-asparaginase, an enzyme widely used in cancer chemotherapy,
      is mainly regulated by carbon catabolite repression and oxygen. This study was
      carried out to understand how different carbon sources and Vitreoscilla
      hemoglobin (VHb) affect the production of this enzyme in Pseudomonas aeruginosa
      and its VHb-expressing recombinant strain (PaJC). Both strains grown with various
      carbon sources showed a distinct profile of the enzyme activity. Compared to no
      carbohydrate supplemented medium, glucose caused a slight repression of L
      asparaginase in P. aeruginosa, while it stimulated it in the PaJC strain.
      Glucose, regarded as one of the inhibitory sugars for the production L
      asparaginase by other bacteria, was determined to be the favorite carbon source
      compared to lactose, glycerol and mannitol. Furthermore, contrary to common
      knowledge of oxygen repression of L-asparaginase in other bacteria, oxygen uptake
      provided by VHb was determined to even stimulate the L-asparaginase synthesis by
      P. aeruginosa. This study, for the first time, shows that in P. aeruginosa
      utilizing a recombinant oxygen uptake system, VHb, L-asparaginase synthesis is
      stimulated by glucose and other carbohydrate sources compared to the host strain.
      It is concluded that carbon catabolite and oxygen repression of L-asparaginase in
      fermentative bacteria is not the case for a respiratory non-fermentative
      bacterium like P. aeruginosa.

PMID- 16892257
TI  - Editorial: food is more than a magic word. There is enough food for all of us.

PMID- 16892251
TI  - Production of D-arabitol by a metabolic engineered strain of Bacillus subtilis.
AB  - A novel method for D-arabitol production with a metabolically engineered Bacillus
      subtilis strain is described. A known transketolase-deficient and D-ribose
      producing mutant of B. subtilis (ATCC 31094) was further modified by disruption
      of its rpi (D-ribose phosphate isomerase) gene to create a D-ribulose- and D
      xylulose-producing B. subtilis strain. Expression of the D-arabitol phosphate
      dehydrogenase gene of Enterococcus avium in the D-ribulose- and D-xylulose
      producing strain resulted in a strain of B. subtilis capable of converting D
      glucose to D-arabitol with a high yield (38%) and little by-product formation.

PMID- 16892263
TI  - Meeting report: eating what chimpanzees eat.

PMID- 16892264
TI  - Patents: patenting of stem cell related inventions in Europe.

PMID- 16892265
TI  - An anthocyanin/polyphenolic-rich fruit juice reduces oxidative DNA damage and
      increases glutathione level in healthy probands.
AB  - Oxidative cell damage is involved in the pathogenesis of atherosclerosis, cancer,
      diabetes and other diseases. Uptake of fruit juice with especially high content
      of antioxidant flavonoids/polyphenols, might reduce oxidative cell damage.
      Therefore, an intervention study was performed with a red mixed berry juice
      [trolox equivalent antioxidative capacity (TEAC): 19.1 mmol/L trolox] and a
      corresponding polyphenol-depleted juice (polyphenols largely removed, TEAC 2.4
      mmol/L trolox), serving as control. After a 3-week run-in period, 18 male
      probands daily consumed 700 mL juice, and 9 consumed control juice, in a 4-week
      intervention, followed by a 3-week wash-out. Samples were collected weekly to
      analyze DNA damage (comet assay), lipid peroxidation (plasma malondialdehyde:
      HPLC/fluorescence; urinary isoprostanes: GC-MS), blood glutathione
      (photometrically), DNA-binding activity of nuclear factor-kappaB (ELISA) and
      plasma carotenoid/alpha-tocopherol levels (HPLC-DAD). During intervention with
      the fruit juice, a decrease of oxidative DNA damage (p<5x10(-4)) and an increase
      of reduced glutathione (p<5x10(-4)) and of glutathione status (p<0.05) were
      observed, which returned to the run-in levels in the subsequent wash-out phase.
      The other biomarkers were not significantly modulated by the juice supplement.
      Intervention with the control juice did not result in reduction of oxidative
      damage. In conclusion, the fruit juice clearly reduces oxidative cell damage in
      healthy probands.

PMID- 16892266
TI  - Yoghurt fermentation at elevated temperatures by strains of Streptococcus
      thermophilus expressing a small heat-shock protein: application of a two-plasmid
      system for constructing food-grade strains of Streptococcus thermophilus.
AB  - Streptococcus thermophilus S4 expressing a small heat-shock protein from the
      plasmid pSt04-encoded copy of shsp, is able to carry out fermentation at elevated
      temperature, i.e., at 50 degrees C. In yoghurt culture together with
      Lactobacillus delbrueckii subsp. bulgaricus, fermentation at elevated temperature
      results in a mild yoghurt with low post-acidification and improved stability of
      the starter bacteria during storage at 4 degrees C. To transfer pSt04 into
      commercial S. thermophilus yoghurt starter strains, a two-plasmid system was
      constructed. A helper plasmid providing a selectable antibiotic marker, but
      relying on the repA gene of pSt04, was transformed together with pSt04. After
      isolation of transformants, the helper plasmid was readily lost upon incubation
      of transformants in antibiotic-free medium, thus yielding food-grade strains
      carrying pSt04 only. Successful application of the system was demonstrated.

PMID- 16892267
TI  - Parameters affecting the adsorption of plantaricin 423, a bacteriocin produced by
      Lactobacillus plantarum 423 isolated from sorghum beer.
AB  - Plantaricin 423 is bactericidal to logarithmic and stationary-phase cells of
      Enterococcus sp. HKLHS and L. sakei DSM 20017. Detection of extracellular DNA and
      beta-galactosidase suggests that the mode of action is most probably by
      destabilizing of the cell membrane. Adsorption of plantaricin 423 to target cells
      ranged from 17% for Streptococcus caprinus ATCC 700066 to 67% for Lactobacillus
      plantarum LMG 13556, Lactobacillus curvatus DF38, Listeria innocua LMG 13568 and
      Lactobacillus sakei DSM 20017. Treatment of Enterococcus sp. HKLHS and L. sakei
      DSM 20017 with Triton X-100, Triton X-114 and chloroform increased the adsorption
      of plantaricin.

PMID- 16892268
TI  - Human and bovine lactoferrins in the milk of recombinant human lactoferrin
      transgenic dairy cows during lactation.
AB  - Seven Friesian human lactoferrin (hLf)-transgenic primiparous dairy cows
      expressing recombinant hLf (rhLf) in their milk were included in the study. After
      calving, concentrations of rhLf and bovine LF (bLf) in the milk, somatic cell
      count and milk yield were determined. The concentration of rhLf was found to be
      constant, about 2.9 mg/mL, throughout the early lactation period of 3 months. The
      concentration of bLf in colostrum was higher after calving, but decreased rapidly
      during the first days of lactation. The mean concentration of bLf was 0.15 mg/mL,
      but concentrations varied between cows from 0.07 mg/mL to 0.26 mg/mL. Based on
      that, it may be possible to improve the non-specific host defence mechanism in
      the mammary gland of dairy cows by enhancing the content of rhLf in the milk.

PMID- 16892269
TI  - Engineering and biotechnological aspects for the manufacturing of high quality
      fried potato products.
AB  - Fried potato products have become very popular foods over the last decades. High
      quality standards have been established for these products by the food industry
      including uniform brown color and crispness. During frying, Maillard reactions
      takes place which contribute to color and taste development in these products.
      However, safety aspects are also influenced by these reactions, e.g., acrylamide
      formation. Maintaining high safety standards as well as the expected quality
      requires systematic research based on an integrated approach including all
      relevant variables, e.g., raw material properties, processing conditions and
      equipment concepts. Selected results of these investigations are presented and
      discussed, regarding influence of composition, e.g., precursor levels for
      Maillard reactions, treatment of raw materials and addition of reactants to
      frying fat. It has been demonstrated that a combined treatment of the potato
      sticks by coating of product surfaces and partial pre-drying can be successfully
      applied to produce well-browned French fries with lower acrylamide contents.
      Reductions up to 75% could be reached compared to samples without treatment.
      Furthermore, addition of a water/oil emulsion containing glutamine in the aqueous
      phase has been shown to influence Maillard reactions at the product surface,
      resulting in lower acrylamide contents at the same state of browning.

PMID- 16892271
TI  - Effect of molecular crowding on DNA polymerase activity.
AB  - Live cells contain high concentrations of macromolecules, but almost all
      experimental biochemical data have been generated from dilute solutions that do
      not reflect conditions in vivo. To understand biomolecular behavior in vivo,
      properties studied in vitro are extrapolated to conditions in vivo; however, the
      molecular conditions within live cells are inherently crowded. The present study
      investigates the effect of molecular crowding on DNA polymerase activity using
      polyethylene glycol PEG of various molecular weights as a crowding agent.
      Polymerase activity assays under various conditions demonstrated that the
      activities of T7 and Taq DNA polymerases depend on the molecular weight and
      concentration of the crowding agent. Furthermore, equilibrium and kinetic
      analyses demonstrated that the binding affinity and catalytic activity of the
      polymerase increase and decrease, respectively, with increasing PEG
      concentrations. Based on quantitative parameters of the polymerase reactions, we
      improved the efficiency of PCR amplification under conditions of molecular
      crowding. These results suggest that quantitative measurements of biomolecular
      structure and function are useful for understanding the behavior of biomolecules
      in vivo and for biotechnology applications in vitro.

PMID- 16892270
TI  - Essential fatty acids: biochemistry, physiology and pathology.
AB  - Essential fatty acids (EFAs), linoleic acid (LA), and alpha-linolenic acid (ALA)
      are essential for humans, and are freely available in the diet. Hence, EFA
      deficiency is extremely rare in humans. To derive the full benefits of EFAs, they
      need to be metabolized to their respective long-chain metabolites, i.e., dihomo
      gamma-linolenic acid (DGLA), and arachidonic acid (AA) from LA; and
      eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from ALA. Some of
      these long-chain metabolites not only form precursors to respective
      prostaglandins (PGs), thromboxanes (TXs), and leukotrienes (LTs), but also give
      rise to lipoxins (LXs) and resolvins that have potent anti-inflammatory actions.
      Furthermore, EFAs and their metabolites may function as endogenous angiotensin
      converting enzyme and 3-hdroxy-3-methylglutaryl coenzyme A reductase inhibitors,
      nitric oxide (NO) enhancers, anti-hypertensives, and anti-atherosclerotic
      molecules. Recent studies revealed that EFAs react with NO to yield respective
      nitroalkene derivatives that exert cell-signaling actions via ligation and
      activation of peroxisome proliferator-activated receptors. The metabolism of EFAs
      is altered in several diseases such as obesity, hypertension, diabetes mellitus,
      coronary heart disease, schizophrenia, Alzheimer's disease, atherosclerosis, and
      cancer. Thus, EFAs and their derivatives have varied biological actions and seem
      to be involved in several physiological and pathological processes.

PMID- 16892272
TI  - Lignin degradation by a novel peptide, Gt factor, from brown rot fungus
      Gloeophyllum trabeum.
AB  - Gt factor, a pure component isolated from Gloeophyllum trabeum, was used to
      decompose lignin materials. The radical intermediates, degradation products and
      structural changes of treated materials were analyzed by infrared spectrum, NMR
      and electron paramagnetic resonance, etc. The results indicate that Gt factor
      makes an oxidative attack on lignin via HO., which might be the initial step in
      lignocellulose degradation by brown rot fungus.

PMID- 16892273
TI  - Agrobacterium-mediated transformation of sea urchin embryos.
AB  - Agrobacterium-mediated transformation of higher plants is a well-known and
      powerful tool for transgene delivery to plant cells. In the present work, we
      studied whether Agrobacterium can transfer genetic information to animal (sea
      urchin) embryos. Sea urchin embryos were co-cultivated with A. tumefaciens
      strains carrying binary vectors containing the nptII marker gene and
      agrobacterial rolC and rolB oncogenes. Bacterial plasmid T-DNA-sea urchin DNA
      junction sites were identified in the genome of these embryos, thus indicating
      successful transformation. The nptII and both rol genes were expressed in the
      transformed embryos. The processes of transgene integration and transgene
      expression were suppressed when Agrobacteria contained mutated virA, virB or virG
      genes, suggesting that Agrobacterium transforms sea urchin cells by a mechanism
      similar to that which mediates T-DNA transfer to plants. Some of the embryos co
      cultivated with Agrobacterium developed teratoma-like structures. The ability of
      Agrobacterium strains to trigger formation of teratoma-like structures was
      diminished when they contained the mutated vir genes. In summary, our results
      demonstrate that Agrobacterium is able to transform animal (sea urchin) embryonic
      cells, thus indicating a potential of this natural system for gene delivery to
      animal hosts. We also discuss the possibility of horizontal gene transfer from
      Agrobacterium to marine invertebrates.

PMID- 16892274
TI  - Two-step protocol to incorporate cells in thermoresponsive hydrogels.
AB  - One of the stumbling blocks in the formation of a thermoresponsive cell-hydrogel
      hybrid (TCH) is the efficient incorporation of cells in thermoresponsive
      hydrogels (TH) using traditional top-down (i.e., cells penetrate in the pre-set
      gels from top surface) approach. This approach is slow and tedious because the
      hydrogel needs to soak in the cells culture for a long time to allow cells to
      penetrate from the gel surface in to the bulk of the gel. In addition, cell
      incorporation into TH is difficult because elevated dissolution temperatures of
      gelators are detrimental to cell viability, whereas the highly viscous gel state
      that formed at ambient temperatures retards the penetration of cells. We propose
      a bottom-up approach (i.e., cells mixed prior to gel setting) using a novel two
      step protocol. The first step is the rapid cooling of the agarose solution from
      its dissolution temperature (98 degrees C) to 37 degrees C and equilibrating for
      3-4 min. The second step is the mixing of fibroblasts with the agarose solution
      and natural cooling to the room temperature to form the TCH. With this novel
      protocol, 90% of fibroblasts are found to be trapped in the cell-gel hybrid.

PMID- 16892275
TI  - Sequence quality is maintained after multiple displacement amplification of non
      invasively obtained macaque semen DNA.
AB  - Whole genome amplification protocols are revolutionizing the fields of molecular
      and conservation biology as they open the possibility of obtaining a large number
      of copies of a complete genome from minute amounts of sample. Multiple
      displacement amplification (MDA) is a whole genome amplification technique based
      on the properties of the phi29 DNA polymerase, which leads to a uniform
      representation of the genome with very low error rates. In this study we
      performed MDA on 28 macaque DNA samples extracted from blood or non-invasively
      collected semen from which we obtained mitochondrial control region sequences
      both before and after MDA. The length of the readable sequences was longer for
      the original samples than for the MDA products, but the number of unresolved
      positions was comparable both before and after MDA. We conclude that the MDA
      technique is useful for increasing the amount of DNA for sequencing mitochondrial
      regions in the case of non-invasively collected semen samples.

PMID- 16892283
TI  - Perspectives: biotechnology in Czech Republic, the past and the future.

PMID- 16892287
TI  - Marine glycosyl hydrolases in the hydrolysis and synthesis of oligosaccharides.
AB  - The marine ecosystem can be considered a rather unexplored source of biological
      material (e.g. natural substances with therapeutic activity) and can also be a
      surprising source of enzymes carrying new and interesting catalytic activities to
      be applied in biocatalysis. The use of glycosyl hydrolases from marine
      environments dates back to the end of the 1960s and was mainly focused on the
      development of sensitive and reliable hydrolytic methods for the analysis of
      sugar chains. As a result not all the benefits of a particular enzymatic activity
      have been investigated, especially regarding the transglycosylation potential of
      these enzymes for the synthesis of glycosidic bonds. In this review, the
      potential of marine sources will be demonstrated reporting on the few examples
      found in literature for the synthesis and hydrolysis of biologically relevant
      oligosaccharides catalyzed by glycosyl hydrolases of marine origin. Particular
      emphasis is given to the synthesis of glycosidic bonds, which is easy by the use
      of glycosyl hydrolases. Further aspects considered in this review are
      applications of these biocatalysts for vegetal waste treatment in recovering
      useful materials, for structural identification and for preparation of target
      materials from new purified polysaccharides, for the synthesis or modification of
      food-related compounds and for glycobiology related studies.

PMID- 16892289
TI  - Directed evolution of an industrial biocatalyst: 2-deoxy-D-ribose 5-phosphate
      aldolase.
AB  - Aldolases are emerging as powerful and cost efficient tools for the industrial
      synthesis of chiral molecules. They catalyze enantioselective carbon-carbon bond
      formations, generating up to two chiral centers under mild reaction conditions.
      Despite their versatility, narrow substrate ranges and enzyme inactivation under
      synthesis conditions represented major obstacles for large-scale applications of
      aldolases. In this study we applied directed evolution to optimize Escherichia
      coli 2-deoxy-D-ribose 5-phosphate aldolase (DERA) as biocatalyst for the
      industrial synthesis of (3R,5S)-6-chloro-2,4,6-trideoxyhexapyranoside. This
      versatile chiral precursor for vastatin drugs like Lipitor (atorvastatin) is
      synthesized by DERA in a tandem-aldol reaction from chloroacetaldehyde and two
      acetaldehyde equivalents. However, E. coli DERA shows low affinity to
      chloroacetaldehyde and is rapidly inactivated at aldehyde concentrations useful
      for biocatalysis. Using high-throughput screenings for chloroacetaldehyde
      resistance and for higher productivity, several improved variants have been
      identified. By combination of the most beneficial mutations we obtained a tenfold
      improved variant compared to wild-type DERA with regard to (3R,5S)-6-chloro-2,4,6
      trideoxyhexapyranoside synthesis, under industrially relevant conditions.

PMID- 16892288
TI  - Structure-guided consensus approach to create a more thermostable penicillin G
      acylase.
AB  - The thermostabilization of penicillin G acylase (PGA) is a difficult problem due
      to the large size of the protein and its complex maturation process. We developed
      a data-driven protein design method that requires fewer homologous sequences than
      the traditional consensus approach and utilizes structural information to limit
      the number of variants created. Approximately 50% of our 21 single-point mutants
      were found experimentally to be more thermostable than the wild-type PGA, two had
      almost threefold longer half-life at 50 degrees C, with very little effect on
      activity. An analysis of four programs that predict the thermostability conferred
      by point mutations shows little agreement between the programs and with the
      experimental data, emphasizing that the chosen stabilizing mutations are very
      difficult to predict, but that our data-driven design method should prove useful.

PMID- 16892290
TI  - Comparison of genetic algorithms for experimental multi-objective optimization on
      the example of medium design for cyanobacteria.
AB  - In this work, two different genetic algorithms were applied to improve culture
      media composition for the autotrophic cyanobacteria Synechococcus PCC 7942.
      Biomass yield and conversion of the asymmetric reduction of 2', 3', 4', 5', 6'
      pentafluoroacetophenone were considered as simultaneous objectives, resulting in
      a multi-objective optimization problem. Even when similar performances of both
      algorithms were observed, it could be shown that a novel strength pareto approach
      was able to achieve remarkable results with a reduced number of experiments (160
      instead of 320). Handling a high number of media components (13), their
      concentrations were adjusted, delivering high improvements in comparison to the
      standard BG 11 culture media. The quality of the Synechococcus biocatalyst could
      be increased up to fivefold compared to the initial state of the optimization.

PMID- 16892291
TI  - Modification of the membrane-bound glucose oxidation system in Gluconobacter
      oxydans significantly increases gluconate and 5-keto-D-gluconic acid
      accumulation.
AB  - Gluconobacter oxydans DSM 2343 (ATCC 621H)catalyzes the oxidation of glucose to
      gluconic acid and subsequently to 5-keto-D-gluconic acid (5-KGA), a precursor of
      the industrially important L-(+)-tartaric acid. To further increase 5-KGA
      production in G. oxydans, the mutant strain MF1 was used. In this strain the
      membrane-bound gluconate-2-dehydrogenase activity, responsible for formation of
      the undesired by-product 2-keto-D-gluconic acid, is disrupted. Therefore, high
      amounts of 5-KGA accumulate in the culture medium. G. oxydans MF1 was equipped
      with plasmids allowing the overexpression of the membrane-bound enzymes involved
      in 5-KGA formation. Overexpression was confirmed on the transcript and enzymatic
      level. Furthermore, the resulting strains overproducing the membrane-bound
      glucose dehydrogenase showed an increased gluconic acid formation, whereas the
      overproduction of gluconate-5-dehydrogenase resulted in an increase in 5-KGA of
      up to 230 mM. Therefore, these newly developed recombinant strains provide a
      basis for further improving the biotransformation process for 5-KGA production.

PMID- 16892292
TI  - Operational concept for the improved synthesis of (R)-3,3'-furoin and related
      hydrophobic compounds with benzaldehyde lyase.
AB  - Biphasic reaction systems for enzyme catalysis are an elegant way to overcome
      limited solubility and stability of reactants and facilitate continuous
      processes. However, many synthetically useful enzymes are not stable in biphasic
      systems of water and organic solvent. The entrapment in polymer beads of
      polyvinyl alcohol has been shown to enable the stable operation of enzymes
      unstable in conventional biphasic reaction systems. We report the extension of
      this concept to continuous operation in a fluidised bed reactor. The enzyme
      benzaldehyde lyase was used for the continuous synthesis of enantiopure (R)-3,3'
      furoin. The results show enhanced stability with half-life times under operation
      conditions of more than 100 h, as well as superior enzyme utilisation in terms of
      productivity. Furthermore, racemisation and oxidation of the product could be
      successfully prevented under the non-aqueous and inert reaction conditions.

PMID- 16892293
TI  - Nitrile hydrolysis activity of Rhodococcus erythropolis NCIMB 11540 whole cells.
AB  - The nitrile hydrolyzing properties of the bacterium strain Rhodococcus
      erythropolis NCIMB 11540 have been investigated. Using whole cells of the
      microorganism, a wide variety of aromatic and aliphatic cyanide-containing
      substrates was successfully hydrolyzed to the corresponding amide or acid. In the
      case of dicyanides, selective monohydrolysis took place, which was further
      explored in the desymmetrization of malononitriles resulting in the corresponding
      cyano amides in enantiomeric excesses of up to 98%.

PMID- 16892294
TI  - Influence of water-miscible organic solvents on kinetics and enantioselectivity
      of the (R)-specific alcohol dehydrogenase from Lactobacillus brevis.
AB  - Using the organic solvents acetonitrile and 1,4-dioxane as water-miscible
      additives for the alcohol dehydrogenase (ADH)-catalyzed reduction of butan-2-one,
      we investigated the influence of the solvents on enzyme reaction behavior and
      enantioselectivity. The NADP(+)-dependent (R)-selective ADH from Lactobacillus
      brevis (ADH-LB) was chosen as biocatalyst. For cofactor regeneration, the
      substrate-coupled approach using propan-2-ol as co-substrate was applied.
      Acetonitrile and 1,4-dioxane were tested from mole fraction 0.015 up to 0.1.
      Initial rate experiments revealed a complex kinetic behavior with enzyme
      activation caused by the substrate butan-2-one, and increasing K(M) values with
      increasing solvent concentration. Furthermore, these experiments showed an
      enhancement of the enantioselectivity for (R)-butan-2-ol from 37% enantiomeric
      excess (ee) in pure phosphate buffer up to 43% ee in the presence of 0.1 mol
      fraction acetonitrile. Finally, the influence of the co-solvents on water
      activity of the reaction mixture and on enzyme stability was investigated.

PMID- 16892295
TI  - Immobilization of enzymes in microtiter plate scale.
AB  - Different immobilization methods were adapted to the 96-well microtiter plate
      scale using esterases as model enzymes. The methods tested were based on
      adsorption, coprecipitation, aggregation and covalent bonding. The protein
      covered microcrystals proved to be the best method in terms of yield and
      expressed activity for the test reaction, which was the alcoholysis of p
      nitrophenyl acetate with 1-propanol under anhydrous conditions.

PMID- 16892301
TI  - Clinical outcome of infants with confined placental mosaicism and intrauterine
      growth restriction of unknown cause.
AB  - The purpose of this study was to know a role of confined placental mosaicism
      (CPM) in perinatal outcome and postnatal growth and development of infants with
      intrauterine growth restriction (IUGR). We selected 50 infants with IUGR (<-2.0
      SD) from 3,257 deliveries in a regional medical center during the past 10-year
      period, and carried out cytogenetic and molecular analyses in their placenta and
      cord blood. Of the 50 infants, 8 had CPM (CPM group) and were composed of five
      single (CPM2, 7, 13, 22, and 22), one double (CPM7/13), and one quadruple trisomy
      (CPM2/7/15/20), and one partial monosomy [del(2)(p16)]. The origin of an extra
      chromosome of trisomy was maternal in six cases of CPM, paternal in one, and
      undetermined in one. Uniparental disomy in disomic cell lines was ruled out in
      all these mosaics. We also compared clinical parameters for perinatal outcome
      between CPM group and infants without evidence of CPM (non-CPM group), such as
      maternal and gestational age, birth weight, Apgar score, cord blood pH, gender,
      and uterine artery patterns by Doppler ultrasonography, as well as weight,
      height, and developmental quotient (DQ) by Denver Developmental Screening Test at
      age 12 months. Phenotypic abnormalities were noted in two infants with CPM and
      three infants of non-CPM group: One with CPM22 had ASD and hypospadias, one with
      CPM7/13 had Russell-Silver syndrome (RSS), and one without CPM had polydactyly,
      and two without CPM had RSS. All but one infant with CPM are alive at age 12
      months. Among the clinical parameters, the detection rate of a notch waveform
      pattern of the uterine artery was significantly higher in the CPM group (P <
      0.05). However, no significant difference was noted in perinatal outcome of
      pregnancy and in DQ at age 12 months between the two groups. Interestingly, short
      stature (<-2 SD) at age 12 months was more frequently seen in CPM group (7/8
      infants with CPM vs. 8/15 infants without CPM), although no statistically
      significant difference was obtained. The information obtained will be useful for
      perinatal care and genetic counseling for infants with IUGR and CPM.

PMID- 16892303
TI  - Sedaghatian spondylometaphyseal dysplasia with pachygyria and absence of the
      corpus callosum.
AB  - We report on a female infant with a metaphyseal dysplasia and a neuronal
      migration abnormality consistent with a diagnosis of Sedaghatian
      spondylometaphyseal dysplasia. This child, born to nonconsanguineous Caucasian
      parents, was hypotonic from birth and experienced recurrent cyanotic episodes
      within a few hours of delivery. Cerebral imaging revealed absence of the corpus
      callosum and marked frontotemporal pachygyria. She developed seizures on day 14
      of life and died at the age of 17 days. Our case highlights the possibility for
      neuronal migration abnormalities in Sedaghatian spondylometaphyseal dysplasia and
      suggests a novel association of the disorder with agenesis of the corpus
      callosum.

PMID- 16892302
TI  - Identification of a novel polymorphism--the duplication of the NPHP1
      (nephronophthisis 1) gene.

PMID- 16892304
TI  - Major feeding difficulties in the first reported case of interstitial 20q11.22
      q12 microdeletion and molecular cytogenetic characterization.
AB  - We report on a 4-year-old female presenting with intrauterine growth retardation,
      facial dysmorphic features, major feeding difficulties with severe diarrhea and
      vomiting, mental retardation with abnormal behavior and hypertonia. Feeding
      difficulties were the most invalidating features with absent oral intake
      requiring persistent enteral feeding. Standard cytogenetic studies were normal,
      but high-resolution chromosome analyses revealed a small de novo interstitial
      deletion of the long arm of chromosome 20, 46,XX,del(20)(q11.21q12). The deletion
      was confirmed using metaphase comparative genomic hybridization (CGH) and
      multicolor high resolution banding (mBAND). The deletion breakpoints were
      characterized using FISH analyses with YACs, PACs, and BACs clones located in the
      deleted and adjacent regions. A 6.6-Mb deleted region between markers D20S815
      (20q11.22) and D20S435 (20q12) could be delineated. None of the nine previously
      reported cases with interstitial 20q deletion found in the literature involve the
      same breakpoints. This report further emphasizes the indication of high
      resolution chromosome analyses in children with syndromic mental retardation. The
      description of additional cases would be useful in order to better characterize
      the phenotype of patients with proximal interstitial 20q deletion.

PMID- 16892310
TI  - ImmunoTrack: the novel antibody-based technology for tracing in animal health.
AB  - This paper describes a novel antibody-based livestock movement control tool and
      method of meat allocation, both in livestock husbandry as well as during the meat
      processing chain. Immuno Track fulfills diverse prerequisites and meets
      regulatory demands which are substantial for a successful monitoring technology:
      (i) the induction of long-lasting antibody responses detectable onsite throughout
      the whole mast period of pigs, (ii) a single immunization injection with protein
      derivatives is sufficient to evoke a strong epitope-specific antibody response,
      and (iii) the complete degradation of the protein markers after the antibody
      response has been triggered in meatproducing animals such as cattle or pigs.
      There are diverse fields of application for the Immuno-Track marker technology,
      such as in quality meat programs, as compliance markers for animal vaccines or as
      a tool for verification of origin. Combination of this monitoring technology with
      the husbandry and identification databases for cattle and pigs within the
      European Community will lead to greater transparency in meat production, thereby
      regaining consumers' trust in concomitant structures of the meat-producing
      industry.

PMID- 16892311
TI  - Formation of galacto-oligosaccharides during lactose hydrolysis by a novel beta
      galactosidase from the moderately thermophilic fungus Talaromyces thermophilus.
AB  - Discontinuous and continuous processes of lactose hydrolysis and concomitant
      galacto-oligosaccharide (GalOS) formation were studied. To this end a wide
      experimental range of the main variables was evaluated, including the initial
      lactose concentration, the degree of lactose conversion, the pH value and the
      temperature for discontinuous transformations, while the initial lactose
      concentration and the feed rate were varied for the continuous process. For both
      processes a high-initial lactose concentration proved to be advantageous for the
      formation of GalOS. The maximum amount of GalOS (100 g/L, corresponding to a
      yield of approximately 50% based on the initially employed lactose) was obtained
      after 8 h of incubation when using 200 g/L lactose as substrate and 90% lactose
      hydrolysis was observed. GalOS productivity in the continuous process (g/L.h) was
      enhanced by an increase of the flow rate. The maximum GalOS productivity of 70
      g/L.h was obtained at a flow rate of 24 mL/h when using a reactor with a total
      working volume of 21 mL. As was evident from these experiments, this beta
      galactosidase from a moderately thermophilic fungus showed a strong
      transgalactosylation activity and can be used for the formation of GalOS, sugars
      that are of considerable interest for functional food applications because of
      their presumed healthpromoting effects.

PMID- 16892312
TI  - Evaluation of a genomics platform for cross-species transcriptome analysis of
      recombinant CHO cells.
AB  - Microarray technology for mammalian cells has been utilized mainly for humans,
      mouse, and rat gene expression analysis. In this approach the feasibility of
      cross-species hybridization experiments using Chinese hamster ovary (CHO) cells
      was evaluated. Sequence alignments of available data for CHO were performed
      against mouse and rat transcripts to determine the homology between the
      investigated species. We implemented a probability model based on this homology
      in order to estimate the chance for successful hybridization using Agilent's 60
      mer oligonucleotide platform. Heat-shock expression data from CHO, mouse 3T3, and
      rat A10 cells were generated to determine intraspecies variability,
      reproducibility, and specificity in order to assess the accuracy of this method.
      Detected signature genes, in particular from studies with the mouse arrays,
      showed a reliable similarity between these two rodents and were confirmed by
      quantitative RT-PCR. Our findings provide evidence that cross-species analysis
      can be a useful tool to study gene expression profiles of related organisms for
      which species-specific microarrays are not available.

PMID- 16892313
TI  - A rapid, high content, in vivo model of glucocorticoid-induced osteoporosis.
AB  - Glucocorticoid-induced osteoporosis (GIOP) is a major clinical problem given the
      widespread use of steroids and limited efficacy of biphosphonates. Existing
      animal models of GIOP are both slow and expensive. Hence, there is a need both
      for adjunctive modelling systems, as well as more efficacious therapies for the
      treatment of GIOP. We have addressed this issue through the creation of a
      zebrafish model of GIOP, which can be used for 96-well plate in vivo screening
      with an assay time of 5 days. The model demonstrates key similarities to human
      GIOP including a partial response to bisphosphonates. The ability to extract
      detailed pharmacological data, including concentration-response analyses, enables
      the screening and ranking of candidate therapeutic compounds. In addition, the
      zebrafish model is highly relevant for pathway dissection through genetic
      knockdown and overexpression studies.

PMID- 16892314
TI  - Genomic DNA of leukemic patients: target for clinical diagnosis of MLL
      rearrangements.
AB  - Genomic DNA is the optimal resource to analyze questions concerning genetic
      changes that are related to oncogenesis. This article tries to summarize recent
      efforts to analyze chromosomal changes that trigger the development of human
      acute myeloid and lymphoblastic leukemias. The aim of this study was to establish
      an universal method that enables the identification and characterization of
      chromosomal translocations of the human MLL gene at the genomic nucleotide level.
      Chromosomal translocations of the MLL gene are the result of illegitimate
      recombination events in hematopoietic stem or precursor cells, strictly
      associated with the onset of highly malignant leukemic diseases. The applied
      technology was able to identify specific fusion alleles that were generated by
      chromosomal translocations, chromosomal deletions, chromosomal inversions and
      partial tandem duplications. Moreover, it allowed us to investigate even highly
      complex genetic changes by applying systematic breakpoint analyses. On the basis
      of these analyses, patient-specific molecular markers were established that
      turned out to be a very good source for monitoring minimal residual disease
      (MRD). MRD analyses control the efficiency and efficacy of current treatment
      protocols and have become a very sensitive molecular tool to monitor therapeutic
      success or failure in individual leukemia patients.

PMID- 16892315
TI  - Radiotracer measurements of protein mass transfer: kinetics in ion exchange
      media.
AB  - We describe a method to measure protein mass transfer kinetics in ion exchange
      adsorbents for preparative chromatography based on the use of radioactively
      labeled protein. The method was developed and evaluated using lysozyme as a test
      protein with the three commercial strong-acid cation exchangers SP-Sepharose-FF,
      SP-Sepharose-XL, and S-HyperD. Iodination with 125I was used to label the
      protein, which was added in trace amounts (approximately 0.1%) to an unlabeled
      protein solution. The solution was recirculated through a shallow bed of the
      adsorbent particles and the radioactivity accumulated in the bed measured with a
      gamma-counter as a function of time. Radiotracer-based kinetics measurements were
      found to be in good agreement with results obtained with a conventional shallow
      bed technique, provided that freshly labeled protein solutions were used. The
      method has advantages in terms of simplicity, ability to deal with adsorption
      from complex mixtures, and the potential for measurements under tracer diffusion
      conditions. Kinetics results obtained for the three different stationary phases
      were generally consistent with previous studies. Protein mass transfer can be
      described by a pore diffusion model with a nearly salt-independent pore
      diffusivity for SP-Sepharose-FF and by a homogeneous diffusion model with a
      saltindependent adsorbed phase diffusivity for S-HyperD. However, it appears that
      a more complex model, accounting for parallel pore and surface diffusion, is
      needed to describe protein mass transfer in SP-Sepharose-XL. The modeling results
      were found to be correlated with the apparent pore sizes determined by inverse
      SEC.

PMID- 16892316
TI  - Using ColE1-derived RNA I for suppression of a bacterially encoded gene:
      implication for a novel plasmid addiction system.
AB  - The use of plasmid DNA for gene therapeutical purposes is a novel technology with
      advantages and drawbacks. One of the required improvements is to avoid antibiotic
      resistance genes or other additional sequences for selection within the plasmid.
      Here, we describe an alternative approach to equip a ColE1 plasmid with a
      regulatory function within the cell, which could be used for selection of plasmid
      carrying cells. No additional sequences are required, since the mechanism is
      based on RNA/RNA antisense interaction involving the naturally occurring RNA I
      derived from the plasmid's origin of replication. The plasmid replicational
      regulatory network was linked to the transcriptional regulatory network of an
      engineered target gene, present on the bacterial chromosome. Thus, gene
      suppression of a reporter could be achieved by mere presence of the ColE1-type
      plasmid pBR322. Proof of this concept was shown in shaker-flask experiments and
      fed-batch fermentation processes. The strategy of regulating gene expression by
      plasmid replication implicates a novel strategy for plasmid selection, as the
      gene to be suppressed could be toxic or growth hampering, providing advantage to
      plasmid carrying host cells.

PMID- 16892317
TI  - Quantitative real-time analysis of HIV-1 gene expression dynamics in single
      living primary cells.
AB  - Studies on the regulation of viral transcription upon infection of the target
      cells have provided important information on the viral and host factors that
      influence pathogenesis. However, these studies have been limited so far to steady
      state analysis of gene expression. Here we report an image based photon-counting
      method that allows real-time quantitative imaging of viral gene expression in
      infected single cells. Employing an HIV-1 vector bearing the firefly luciferase
      reporter gene, we exploited a single cell photon imaging methodology (a
      customized and highly sensitive imaging microscope) to measure viral gene
      expression following integration into a host genome in situ. Our approach reveals
      real-time dynamics of viral gene expression in living HIV natural target cells
      (primary human CD4 T cells and macrophages), and promises itself as a powerful
      tool for quantitative studies on a wide variety of virus-host cell interactions.

PMID- 16892318
TI  - A perspective of synthetic biology: assembling building blocks for novel
      functions.
AB  - Synthetic biology is a recently emerging field that applies engineering
      formalisms to design and construct new biological parts, devices, and systems for
      novel functions or life forms that do not exist in nature. Synthetic biology
      relies on and shares tools from genetic engineering, bioengineering, systems
      biology and many other engineering disciplines. It is also different from these
      subjects, in both insights and approach. Applications of synthetic biology have
      great potential for novel contributions to established fields and for offering
      opportunities to answer fundamentally new biological questions. This article does
      not aim at a thorough survey of the literature and detailing progress in all
      different directions. Instead, it is intended to communicate a way of thinking
      for synthetic biology in which basic functional elements are defined and
      assembled into living systems or biomaterials with new properties and behaviors.
      Four major application areas with a common theme are discussed and a procedure
      (or "protocol") for a standard synthetic biology work is suggested.

PMID- 16892324
TI  - A father of four consecutive trisomic pregnancies with elevated frequencies of
      associated aneuploid sperm.
AB  - A couple with normal somatic karyotypes had four consecutive trisomic
      pregnancies, each involving a different chromosome, of which two children were
      liveborn with confirmed paternal-origin trisomies. The apparently healthy father
      produced abnormally high frequencies of disomic sperm for each of the four
      chromosomes involved in the trisomic pregnancies (P< 0.003, by sperm fluorescence
      in situ hybridization (FISH)). His elevated sperm aneuploidies persisted over a 2
      year period and affected all chromosomes evaluated, suggesting that he had a
      genome-wide defect in meiotic disjunction. He also had the highest frequencies of
      aneuploid sperm reported for any healthy man to date. His frequencies of
      aneuploid sperm were comparable to the peak frequencies of the transient
      responses reported in some cancer patients after receiving aneugenic
      chemotherapies. These findings indicate that apparently healthy men can produce
      abnormally high frequencies of sperm aneuploidies that suggest that this
      condition may contribute to recurrent trisomic pregnancies.

PMID- 16892325
TI  - Additional evidence that PTPN11 mutations play only a minor role in the
      pathogenesis of non-syndromic atrioventricular canal defect.

PMID- 16892326
TI  - A novel 8.5 MB dup(1)(p34.1p34.3) characterized by FISH in a child presenting
      with congenital heart defect and dysmorphic features.
AB  - Chromosome duplications involving 1p are rarely reported but are apparently
      associated with short survival as well as congenital malformations and impaired
      development. Several of these have had congenital heart defects, although too few
      patients have been reported with similar breakpoints to characterize a syndrome.
      We present a girl with a novel interstitial duplication in the short arm of
      chromosome 1 [46,XX,dup(1)(p34.1p34.3)]. She presented with congenital heart
      defects at 1 month and by 1 year of age manifested delayed acquisition of motor
      milestones and subsequently of language milestones. By breakpoint-mapping using
      FISH analysis, we determined that her 1p duplication spans 8.5 megabases. Her 1p
      duplication is the smallest reported to date to contain 1p34 in patients with
      congenital heart defect due to abnormalities of heart looping during development.
      Thus, her 8.5 MB duplication provides a target region to search for a potentially
      dosage-sensitive gene(s) causing abnormal heart looping when duplicated. Two
      patients have been reported with duplication including 1p34 but without
      congenital heart defect, and their duplications span all but the distal
      approximately 2 MB segment duplicated in our patient. Thus, within our patient's
      8.5 MB target region for a dosage sensitive gene leading to looping abnormalities
      (and thereby congenital heart defect), the distal 2 MB region might well be the
      region to begin the search.

PMID- 16892327
TI  - Lethal congenital contracture syndrome (LCCS) and other lethal arthrogryposes in
      Finland--an epidemiological study.
AB  - Arthrogryposis multiplex congenita is a heterogeneous group of disorders
      characterized by multiple contractures with an estimated frequency of 1 in 3,000
      births. With improving diagnostic methods, increasing numbers of fetuses with
      arthrogryposis are found. The pathogenetic mechanisms are relatively well known
      but the epidemiology and genetics of the prenatally lethal forms of
      arthrogryposis are less well known. In this study we collected all cases of a
      multiple contractures diagnosed in Finland during 1987-2002 including live born
      infants, stillbirths, and terminated pregnancies. Ninety-two cases of 214
      suffered intrauterine demise (68 selective pregnancy terminations and 24
      stillbirths) and 58 died in infancy. In 141 out of these cases the diagnosis
      could be included within lethal arthrogryposes, with a prevalence of 1 in 6,985
      (1.43/10,000) births. Of these, 59 had spinal cord pathology at autopsy and thus
      were of neurogenic origin. Thirty-nine cases had lethal congenital contracture
      syndrome (LCCS) clinically characterized by total immobility of the fetus at all
      ultrasound examinations (12 weeks or later), multiple joint contractures in both
      upper and lower limbs, hydrops, and fetal death before the 32nd week of
      pregnancy. LCCS is noted as a unique Finnish disorder with a prevalence of 1 in
      25,250 (0.40/10,000) births and is a major cause of lethal arthrogryposis in
      Finland.

PMID- 16892329
TI  - Current developments in HIV chemotherapy.
AB  - HIV infection is the leading cause of death worldwide and despite major advances
      in treatment, more new cases were diagnosed in 2004 than any previous year.
      Current treatment regimens are based on the use of two or more drugs from two or
      more classes of inhibitors termed highly active antiretroviral therapy (HAART).
      Although HAART is capable of suppressing viral loads to undetectable levels,
      problems of toxicity, patient adherence, and particularly the emergence of drug
      resistant viruses continues to spur the development of new chemotherapeutics to
      combat HIV. Clinical candidates from the four existing classes of inhibitors are
      presented in this review along with lead compounds against new viral targets,
      with special emphasis on HIV integrase.

PMID- 16892330
TI  - The hit-to-lead process at Schering AG: strategic aspects.
AB  - Modern organizations conducting drug-discovery programs frequently apply high
      throughput screening to generate novel hit structures for the indications of
      interest. Systematic hit-to-lead processes have been established at most
      pharmaceutical companies to ensure a smooth conversion of hits into high-quality
      lead structures. At Schering AG, a hit-to-lead process with distinct selection
      criteria was introduced in 1999 to identify the best leads possible. The thorough
      evaluation of hits and lead candidates allows risk assessments, which facilitate
      the assignment of valuable resources to those lead-discovery projects with the
      most chances of success. A dedicated hit-to-lead team has been formed to oversee
      the process and to provide guidance to the respective project teams.

PMID- 16892331
TI  - Structure-activity relationships in side-chain-modified epothilone analogues--how
      important is the position of the nitrogen atom?

PMID- 16892332
TI  - Molecular design and chemical synthesis of a highly potent epothilone.

PMID- 16892333
TI  - Aminothiazole derivatives as neuropeptide Y5 receptor ligands: finding the
      balance between affinity and physicochemical properties.

PMID- 16892334
TI  - 2-{3-[2-(4-chlorophenyl)ethoxy]phenylthio}-2-methylpropanoic acid: a fibrate-like
      compound with hypolipidemic and antidiabetic activity.

PMID- 16892335
TI  - Click chemistry on azidoproline: high-affinity dual antagonist for HIV-1 envelope
      glycoprotein gp120.

PMID- 16892336
TI  - Structural remodeling of cocaine: design and synthesis of trisubstituted
      cyclopropanes as selective serotonin reuptake inhibitors.

PMID- 16892337
TI  - An albumin-activated far-red fluorochrome for in vivo imaging.

PMID- 16892338
TI  - Effects of conformational dynamics on predicted protein druggability.

PMID- 16892339
TI  - Prediction of small-molecule binding to cytochrome P450 3A4: flexible docking
      combined with multidimensional QSAR.
AB  - The inhibition of cytochrome P450 3A4 (CYP3A4) by small molecules is a major
      mechanism associated with undesired drug-drug interactions, which are responsible
      for a substantial number of late-stage failures in the pharmaceutical drug
      development process. For a quantitative prediction of associated pharmacokinetic
      parameters, a computational model was developed that allows prediction of the
      inhibitory potential of 48 structurally diverse molecules. Based on the
      experimental structure of CYP3A4, possible binding modes were first sampled by
      using automated docking (Yeti software) taking protein flexibility into account.
      The results are consistent with both X-ray crystallographic data and data from
      metabolic studies. Next, an ensemble of energetically favorable orientations was
      composed into a 4D dataset for use as input for a multidimensional QSAR technique
      (Raptor software). A dual-shell binding-site model that allows an explicit
      induced fit was then generated by using hydrophobicity scoring and hydrogen-bond
      propensity. The simulation reached a cross-validated r2 value of 0.825 and a
      predictive r2 value of 0.659. On average, the predicted binding affinity of the
      training ligands deviates by a factor of 2.7 from the experiment; those of the
      test set deviate by a factor of 3.8 in Ki.

PMID- 16892340
TI  - Design, synthesis, biological evaluation, and molecular modeling studies of TIBO
      like cyclic sulfones as non-nucleoside HIV-1 reverse transcriptase inhibitors.
AB  - TIBO- and TBO-like sulfone derivatives 1 and 2 were designed, synthesized, and
      tested for their ability to block the replication cycle of HIV-1 in infected
      cells. The anti-HIV-1 activities of sulfones 3, which were intermediates in the
      syntheses of 1 and 2, were also evaluated. Surprisingly, the sulfone analogues of
      TIBO R82913 (compounds 1) were inactive, whereas interesting results were
      obtained for truncated derivatives 2. Compound 2 w was the most potent among this
      series in cell-based assays (EC50=0.07 microM, CC50>200 microM, SI>2857). It was
      twofold less potent than R82913, but more selective. An X-ray crystallographic
      analysis was carried out to establish the absolute configuration of 2 w and its
      enantiomer 2 x, which were obtained by semipreparative HPLC of 2 v, one of the
      most potent racemates. Compounds 1-3 were proven to target HIV-1 RT. In fact,
      representative derivatives inhibited recombinant HIV-1 RT in vitro at
      concentrations similar to those active in cell-based assays. 3D QSAR studies and
      docking simulations were developed on TIBO- and TBO-like sulfone derivatives to
      rationalize their anti-HIV-1 potencies and to predict the activity of novel
      untested sulfone derivatives. Predictive 3D QSAR models were obtained with a
      receptor-based alignment by docking of TIBO- and TBO-like derivatives into the
      NNBS of RT.

PMID- 16892341
TI  - Selective indole-based ECE inhibitors: synthesis and pharmacological evaluation.
AB  - Inhibition of the metalloprotease ECE-1 may be beneficial for the treatment of
      coronary heart disease, cancer, renal failure, and urological disorders. A novel
      class of indole-based ECE inhibitors was identified by high throughput screening.
      Optimization of the original screening lead structure 6 led to highly potent
      inhibitors such as 11, which bears a bisaryl amide moiety linked to the indole C2
      position through an amide group. Docking of 11 into a model structure of ECE
      revealed a unique binding mode in which the Zn center of the enzyme is not
      directly addressed by the inhibitor, but key interactions are suggested for the
      central amide group. Testing of the lead compound 6 in hypertensive Dahl S rats
      resulted in a decrease in blood pressure after an initial period in which the
      blood pressure remained unchanged, most probably the result of ET-1 already
      present. Indole derivative 6 also displays a cardio-protective effect in a mouse
      model of acute myocardial infarction after oral administration. The more potent
      chloropyridine derivative 9 antagonizes big-ET-1-induced increase in blood
      pressure in rats at intravenous administration of 3 mg kg-1. All ECE inhibitors
      of the indole class showed high selectivity for ECE over related metalloproteases
      such as NEP and ACE. Therefore, these compounds might have further potential as
      drugs for the treatment of coronary heart diseases.

PMID- 16892342
TI  - Unexpected novel binding mode of pyrrolidine-based aspartyl protease inhibitors:
      design, synthesis and crystal structure in complex with HIV protease.
AB  - At present nine FDA-approved HIV protease inhibitors have been launched to
      market, however rapid drug resistance arising under antiviral therapy calls upon
      novel concepts. Possible strategies are the development of ligands with less
      peptide-like character or the stabilization of a new and unexpected binding
      competent conformation of the protein through a novel ligand-binding mode. Our
      rational design of pyrrolidinedimethylene diamines was inspired by the idea to
      incorporate key structural elements from classical peptidomimetics with a non
      peptidic heterocyclic core comprising an endocyclic amino function to address the
      catalytic aspartic acid side chains of Asp 25 and 25'. The basic scaffolds were
      decorated by side chains already optimized for the recognition pockets of HIV
      protease or cathepsin D. A multistep synthesis has been established to produce
      the central heterocycle and to give flexible access to side chain decorations.
      Depending on the substitution pattern of the pyrrolidine moiety, single-digit
      micromolar inhibition of HIV-1 protease and cathepsin D has been achieved.
      Successful design is suggested in agreement with our modelling concepts. The
      subsequently determined crystal structure with HIV protease shows that the
      pyrrolidine moiety binds as expected to the pivotal position between both
      aspartic acid side chains. However, even though the inhibitors have been equipped
      symmetrically by polar acceptor groups to address the flap water molecule, it is
      repelled from the complex, and only one direct hydrogen bond is formed to the
      flap. A strong distortion of the flap region is detected, leading to a novel
      hydrogen bond which cross-links the flap loops. Furthermore, the inhibitor
      addresses only three of the four available recognition pockets. It achieves only
      an incomplete desolvation compared with the similarly decorated amprenavir.
      Taking these considerations into account it is surprising that the produced
      pyrrolidine derivatives achieve micromolar inhibition and it suggests
      extraordinary potency of the new compound class. Most likely, the protonated
      pyrrolidine moiety experiences strong enthalpic interactions with the enzyme
      through the formation of two salt bridges to the aspartic acid side chains. This
      might provide challenging opportunities to combat resistance of the rapidly
      mutating virus.

PMID- 16892343
TI  - Semisynthesis and screening of a small library of pro-apoptotic squamocin
      analogues: selection and study of a benzoquinone hybrid with an improved
      biological profile.
AB  - Acetogenins of Annonaceae, including squamocin (1), exert spectacular
      cytotoxicity and the most potent inhibition of NADH:ubiquinone oxidoreductase
      known so far. Cell death induced by these natural products was identified as
      apoptosis and was thought to be linked to alterations in mitochondrial function.
      Quinone-squamocin hybrid compounds were semisynthesized and evaluated for their
      pro-apoptotic properties with a screening method based on dissipation of the
      mitochondrial transmembrane potential (DeltaPsim). Herein, we report a short one
      step synthesis of a squamocin carboxylic acid analogue. For the first time on a
      natural product, the radical decarboxylation and quinone addition reaction has
      enabled preparation of a library of squamocin-quinone hybrids and four other
      analogues. Squamoquinone, tenfold more potent than squamocin as an inducer of
      apoptosis, emerged as a promising compound, as it induces apoptosis through a
      mitochondrial caspase-dependent pathway.

PMID- 16892344
TI  - Synthesis and structure-activity relationships of FAAH inhibitors:
      cyclohexylcarbamic acid biphenyl esters with chemical modulation at the proximal
      phenyl ring.
AB  - Fatty acid amide hydrolase (FAAH) is a serine hydrolase that catalyzes the
      intracellular hydrolysis of fatty acid ethanolamides such as anandamide and
      oleoylethanolamide. Targeting this enzyme may have important therapeutic
      potentials owing to the multiple physiological roles of these amides.
      Cyclohexylcarbamic acid biphenyl-3-yl ester (URB524) was one of the most
      promising FAAH inhibitors so far described. We report the modulation of the
      electronic and steric features of the proximal phenyl ring of this compound by
      introducing a series of substituents at the ortho and para positions. pIC50
      values were found to correlate with molecular features thought to be involved in
      the recognition step such as steric hindrance and hydrogen-bonding ability.
      Derivatives with small polar groups at the para position of the proximal phenyl
      ring were slightly better FAAH inhibitors than the parent compound URB524.

PMID- 16892346
TI  - European medicinal chemistry--strategies, targets, and drugs under the spotlight.

PMID- 16892345
TI  - A medicinal-chemistry-guided approach to selective and druglike sigma 1 ligands.
AB  - Based on a medicinal-chemistry-guided approach, three novel series of druglike
      cycloalkyl-annelated pyrazoles were synthesized and display high affinity (pKi>8)
      for the sigma1 receptor. Structure-affinity relationships were established, and
      the different scaffolds were optimized with respect to sigma1 binding and
      selectivity versus the sigma2 receptor and the hERG channel, resulting in
      selective compounds that have Ki values (for sigma1) in the subnanomolar range.
      Selected compounds were screened for cytochrome P450 inhibition (CYP1A2, CYP2A6,
      CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4), metabolic stability
      (rat and human liver microsomes), and cell-membrane permeability (Caco-2). They
      showed favorable in vitro ADME properties as well as favorable calculated
      druglike and experimental physicochemical properties. Furthermore, compounds 7 f
      and 17 a, for example, displayed high selectivity (affinity) for the sigma1
      receptor against a wide range of other receptors (>60). With these valuable tool
      compounds in hand, we are further exploring the role of the sigma1 receptor in
      relevant animal models corresponding to such medicinal indications as drug abuse,
      pain, depression, anxiety, and psychosis.

PMID- 16892349
TI  - Scaffold-hopping potential of ligand-based similarity concepts.

PMID- 16892348
TI  - Efforts toward the total synthesis of tubulysins: new hopes for a more effective
      targeted drug delivery to tumors.

PMID- 16892350
TI  - A potent HIV protease inhibitor identified in an epimeric mixture by high
      resolution protein crystallography.

PMID- 16892352
TI  - Substituted isoxazoles as potent inhibitors of p38 MAP kinase.
AB  - In a continuous effort to develop improved p38 MAP (mitogen-activated protein)
      kinase inhibitors, we focused our attention on the suitability of the isoxazole
      ring as a bioisosteric replacement for the imidazole ring of SB-203580. 3,4- and
      4,5-disubstituted as well as 3,4,5-trisubstituted isoxazole derivatives were
      synthesized. These compounds were tested in an in vitro enzyme-linked
      immunosorbent assay of isolated p38 MAP kinase and for inhibitory potency against
      cytochrome P450. Compound 4 a displays a highly promising profile for development
      as an anti-inflammatory agent owing to its enhanced suppression of cytokine
      release, decreased affinity for cytochrome P450 and a twofold decrease in IC50
      toward isolated p38 MAP kinase.

PMID- 16892351
TI  - In vivo antitumor activity of clitocine, an exocyclic amino nucleoside isolated
      from Lepista inversa.
AB  - A biologically guided fractionation from Lepista inversa (Scop.: Fr.) led to the
      isolation of clitocine, an exocyclic amino nucleoside. This compound and two
      mixtures of beta/alpha anomers (mixture A, 40:60 and mixture B, 80:20) were
      synthesized or isolated depending on the purification procedure. The beta anomer
      and clitocine mixtures A and B showed similar cytotoxic activities with IC50
      values ranging from 20.5 to 42 nM in murine cancer cell lines (3LL and L1210) and
      from 185 to 578 nM in human cancer cell lines (DU145, K-562, MCF7, and U251). An
      in vivo study of mixture B was carried out on 3LL- and L1210-tumor-bearing mice.
      Clitocine solubilized in beta-hydroxypropylcyclodextrin and injected at
      concentrations of 0.5, 3, and 5 mg kg-1 did not significantly increase the
      survival rate and lifespan of 3LL-tumor-bearing mice. In contrast, clitocine
      showed antitumor activity on L1210-tumor-bearing mice with a significant increase
      in lifespan and a decrease in the development of ascites observed at 3 mg kg-1.
      The induction of apoptosis may be the basis of the antitumor activity of
      clitocine against L1210 as suggested by flow-cytometry analysis of cells treated
      in vitro.

PMID- 16892353
TI  - MS-binding assays: kinetic, saturation, and competitive experiments based on
      quantitation of bound marker as exemplified by the GABA transporter mGAT1.
AB  - A new kind of binding assay is described in which the amount of a nonlabeled
      marker bound to the target is quantified by LC-ESI-MS-MS. This new approach was
      successfully implemented with nonlabeled NO 711 as marker and the GABA
      transporter subtype mGAT1 as target. The native marker bound to the target was
      liberated from the receptor protein by methanol denaturation after filtration. A
      reliable and sensitive LC-ESI-MS-MS method for the quantitation of NO 711 was
      developed, and data from mass spectrometric detection were analyzed by nonlinear
      regression. Kinetic MS-binding experiments yielded values for k+1 and k-1, while
      in saturation MS-binding experiments, Kd and Bmax values were determined. In
      competitive MS-binding experiments, Ki values were obtained for various test
      compounds covering a broad range of affinities for mGAT1. All experiments were
      performed in 96-well plate format with a filter plate for the separation step
      which improved the efficiency and throughput of the procedure. The method was
      validated by classical radioligand-binding experiments with the labeled marker
      [3H2]NO 711 in parallel. The results obtained from MS-binding experiments were
      found to be in good agreement with the results of the radioligand-binding assays.
      The new kind of MS-binding assay presented herein is further adapted to the
      conventional radioligand-binding assay in that the amount of bound marker is
      securely quantified. This promises easy implementation in accordance with
      conventional binding assays without the major drawbacks that are inherent in
      radioligand or fluorescence binding assays. Therefore, MS-binding assays are a
      true alternative to classical radioligand-binding assays.

PMID- 16892354
TI  - Synthesis of stable analogues of geranylgeranyl diphosphate possessing a (Z,E,E)
      geranylgeranyl side chain, docking analysis, and biological assays for prenyl
      protein transferase inhibition.
AB  - Herein, we report the synthesis of novel stable analogues of geranylgeranyl
      diphosphate (GGPP), in which the "natural" all-trans geranylgeranyl portion has
      been replaced by a (Z,E,E)-geranylgeranyl chain. The change in configuration and
      consequent change in the relative position of the polar portion with the
      lipophilic side chain did not improve the properties of the E,E,E analogues in
      their inhibition of geranylgeranyl protein transferase I (GGTase I). However, a
      significant level of GGTase I inhibition and selectivity for GGTase I over
      farnesyl transferase (FTase) was maintained the unsubstituted
      phosphonoacetamidoxy derivative 4 a. This has shed light on the relative
      importance of the configuration at the C2=C3 double bond among GGPP derivatives.
      Moreover, the biological activities of all the compounds reported herein, in
      particular the preferential FTase inhibitory activity shown by compound 6, were
      in good agreement with the results of docking analysis.

PMID- 16892355
TI  - Aroyl-pyrrolyl hydroxyamides: influence of pyrrole C4-phenylacetyl substitution
      on histone deacetylase inhibition.
AB  - The novel aroyl-pyrrolyl hydroxyamides 4 a-a' are analogues of the lead compound
      3-(1-methyl-4-phenylacetyl-1H-pyrrol-2-yl)-N-hydroxy-2-propenamide (2) and are
      active as HDAC inhibitors. The benzene ring of 2 was substituted with a wide
      range of electron-donating and electron-withdrawing groups, and the effect was
      evaluated on three HDACs from maize, namely HD2, HD1-B (a class I HDAC), and HD1
      A (a class II HDAC). Inhibition studies show that the benzene 3' and, to a lesser
      extent, 4' positions of 2 were the most suitable for the introduction of
      substituents, with the 3'-chloro (in 4 b) and the 3'-methyl (in 4 k) derivatives
      being the most potent compounds, reaching the same activity as SAHA. Inhibition
      data for 4 b,k against mouse HDAC1 were consistent with those observed in the
      maize enzyme. The substituent insertion on the benzene ring of 2 (compounds 4 a
      a') abated the slight (3-fold) selectivity for class II HDACs displayed by 2.
      Compound 4 b showed interesting, dose-dependent antiproliferative and
      cytodifferentiation properties against human acute promyelocytic leukemia HL-60
      cells.

PMID- 16892356
TI  - Discovery and structure-activity relationship studies of a unique class of HIV-1
      integrase inhibitors.
AB  - HIV-1 integrase (IN) is an essential enzyme for viral replication and a validated
      target for the development of drugs against AIDS. Currently there are no approved
      drugs that target IN. However, new IN inhibitors are under clinical
      investigation. As more IN inhibitors enter human drug trials, there is a growing
      need for the design of novel lead compounds with diverse structural scaffolds and
      promising pharmacokinetic properties to counteract the difficulties observed with
      first-generation IN inhibitors. We have identified a novel class of IN inhibitors
      through the systematic exploration of structure-activity relationships in a
      series of linomide analogues. The predicted bound conformation of the most active
      analogues inside the IN active site also supports the observed structure-activity
      correlation in this new compound class.

PMID- 16892357
TI  - 1-(1-phenethylpiperidin-4-yl)-1-phenylethanols as potent and highly selective 5
      HT2A antagonists.
AB  - The discovery of a novel class of highly potent and selective 5-HT2A antagonists
      is reported herein. Selectivity for the serotonin 5-HT2A receptor was optimized,
      decreasing the affinity of these antagonists toward the adrenergic alpha1 and
      dopaminergic D2 receptors, and especially to the 5-HT2C receptor. A series of
      corresponding 7-substituted indoles is described for the first time as
      serotonergic ligands. The enantiomer R-(+)-1-(4-fluorophenyl)-1-{1-[2-(4
      fluorophenyl)ethyl]piperidin-4-yl} ethanol (R-(+)-74) was identified to have
      superior affinity for the serotonergic 5-HT2A receptor [IC50=0.37 nM] and
      selectivity toward the dopaminergic D2- [IC50=2300 nM], adrenergic alpha1-
      [IC50=1000 nM] and 5-HT2C receptors [IC50=490 nM].

PMID- 16892358
TI  - Highly potent and specific GSK-3beta inhibitors that block tau phosphorylation
      and decrease alpha-synuclein protein expression in a cellular model of
      Parkinson's disease.
AB  - Research by Klein and co-workers suggests that the inhibition of GSK-3beta by
      small molecules may offer an important strategy in the treatment of a number of
      central nervous system (CNS) disorders including Alzheimer's disease, Parkinson's
      disease, and bipolar disorders. Based on results from kinase-screening assays
      that identified a staurosporine analogue as a modest inhibitor of GSK-3beta, a
      series of 3-indolyl-4-indazolylmaleimides was prepared for study in both
      enzymatic and cell-based assays. Most strikingly, whereas we identified ligands
      having poor to high potency for GSK-3beta inhibition, only ligands with a Ki
      value of less than 8 nM, namely maleimides 18 and 22, were found to inhibit Tau
      phosphorylation at a GSK-3beta-specific site (Ser 396/404). Accordingly,
      maleimides 18 and 22 may protect neuronal cells against cell death by decreasing
      the level of alpha-Syn protein expression. We conclude that the GSK-3beta
      inhibitors described herein offer promise in defending cells against MPP+-induced
      neurotoxicity and that such compounds will be valuable to explore in animal
      models of Parkinson's disease as well as in other Tau-related neurodegenerative
      disease states.

PMID- 16892359
TI  - Structural basis for the exceptional in vivo efficacy of bisphosphonate drugs.
AB  - To understand the structural basis for bisphosphonate therapy of bone diseases,
      we solved the crystal structures of human farnesyl pyrophosphate synthase (FPPS)
      in its unliganded state, in complex with the nitrogen-containing bisphosphonate
      (N-BP) drugs zoledronate, pamidronate, alendronate, and ibandronate, and in the
      ternary complex with zoledronate and the substrate isopentenyl pyrophosphate
      (IPP). By revealing three structural snapshots of the enzyme catalytic cycle,
      each associated with a distinct conformational state, and details about the
      interactions with N-BPs, these structures provide a novel understanding of the
      mechanism of FPPS catalysis and inhibition. In particular, the accumulating
      substrate, IPP, was found to bind to and stabilize the FPPS-N-BP complexes rather
      than to compete with and displace the N-BP inhibitor. Stabilization of the FPPS-N
      BP complex through IPP binding is supported by differential scanning calorimetry
      analyses of a set of representative N-BPs. Among other factors such as high
      binding affinity for bone mineral, this particular mode of FPPS inhibition
      contributes to the exceptional in vivo efficacy of N-BP drugs. Moreover, our data
      form the basis for structure-guided design of optimized N-BPs with improved
      pharmacological properties.

PMID- 16892362
TI  - Inhibitors of mitotic kinesins: next-generation antimitotics.

PMID- 16892363
TI  - Design and synthesis of a PSMA inhibitor-doxorubicin conjugate for targeted
      prostate cancer therapy.

PMID- 16892364
TI  - Tuning wasp toxin structure for nicotinic receptor antagonism: cyclohexylalanine
      containing analogues as potent and voltage-dependent blockers.

PMID- 16892365
TI  - Synthesis and pharmacological evaluation of 8- and 9-substituted benzolactam-v8
      derivatives as potent ligands for protein kinase C, a therapeutic target for
      Alzheimer's disease.
AB  - A central element in the pathophysiology of Alzheimer's disease (AD) is the
      formation of amyloid plaques, which result from abnormal processing of the
      amyloid precursor protein (APP). The processing of APP is largely provided by
      three key enzymes, namely the alpha-, beta-, and gamma-secretases. As the latter
      two contribute to the formation of neurotoxic Abeta fragments while alpha
      secretase does not, a decrease in the amyloidogenic products can be brought about
      either by inhibition of the beta- and gamma-secretases or through the activation
      of alpha-secretase. It is now known that the activation of protein kinase C (PKC)
      enhances alpha-secretase activity and therefore represents a possible target for
      the development of agents urgently needed for the treatment of this devastating
      neurodegenerative disorder. In the present study, new benzolactam-V8-based PKC
      activators were synthesized and tested for their binding affinity toward
      PKCalpha. All compounds tested showed binding values in the nanomolar
      concentration range. In accordance with previous publications, 9-substitution
      dramatically increased PKC binding affinity in comparison with the corresponding
      8-substituted analogues. In addition to the location of the side chain on the
      aromatic ring, the binding affinities of these benzolactams were found to depend
      on the orientation, length, and electronic properties of this appendage. An
      interesting decrease in binding affinity was found for the 9-thienyl analogue 13,
      suggesting adverse electronic interactions of the sulfur atom with PKC or parts
      of the cellular membrane.

PMID- 16892366
TI  - An accurate and interpretable bayesian classification model for prediction of
      HERG liability.
AB  - Drug-induced QT interval prolongation has been identified as a critical side
      effect of non-cardiovascular therapeutic agents and has resulted in the
      withdrawal of many drugs from the market. As almost all cases of drug-induced QT
      prolongation can be traced to the blockade of a voltage-dependent potassium ion
      channel encoded by the hERG (the human ether-a-go-go-related gene), early
      identification of potential hERG channel blockers will decrease the risk of
      cardiotoxicity-induced attritions in the later and more expensive development
      stage. Presented herein is a naive Bayes classifier to categorize hERG blockers
      into active and inactive classes, by using a universal, generic molecular
      descriptor system.1 The naive Bayes classifier was built from a training set
      containing 1979 corporate compounds, and exhibited an ROC accuracy of 0.87. The
      model was validated on an external test set of 66 drugs, of which 58 were
      correctly classified. The cumulative probabilities reflected the confidence of
      prediction and were proven useful for the identification of hERG blockers.
      Relative performance was compared for two classifiers constructed from either an
      atom-type-based molecular descriptor or the long range functional class
      fingerprint descriptor FCFP_6. The combination of an atom-typing descriptor and
      the naive Bayes classification technique enables the interpretation of the
      resulting model, which offers extra information for the design of compounds free
      of undesirable hERG activity.

PMID- 16892367
TI  - Prins-type synthesis and SAR study of cytotoxic alkyl chloro dihydropyrans.
AB  - A series of functionalized tetrahydropyran and dihydropyran derivatives was
      synthesized by means of a Prins-type cyclization between unsaturated alcohols and
      several aldehydes. An unprecedented dimer bearing two 4-chloro-5,6-dihydro-2H
      pyran scaffolds was obtained in high yield. A panel of three representative human
      solid tumor cells from diverse origin was used to assess the cytotoxicity of the
      compounds. Overall, the results show the relevance of the chlorovinyl group in
      the biological activity, and 2-alkyl-4-chloro-5,6-dihydro-2H-pyrans represent
      interesting leads for further chemical modifications and biological studies.

PMID- 16892368
TI  - Stable expression of soluble therapeutic peptides in eukaryotic cells by
      multimerisation: application to the HIV-1 fusion inhibitory peptide C46.
AB  - A major drawback of therapeutic peptides is their short half-life, which results
      in the need for multiple applications and high synthesis costs. To overcome this,
      we established a eukaryotic expression system that allows the stable expression
      of small therapeutic peptides by multimerisation. By inserting the sequence
      encoding the therapeutic peptide between a signal peptide and the multimerising
      domain of the alpha-chain from the human C4bp plasma protein, therapeutic
      peptides as small as 5 kDa are secreted as multimers from transfected cells; this
      allows easy purification. As proof of principle, we show that the T20-derived HIV
      1 fusion inhibitory peptide C46 in its multimeric form: i) was efficiently
      secreted, ii) was more stable than the current antiviral drug T20 in vitro and in
      vivo, and iii) inihibited HIV-1 entry with similar efficiency in vitro. Besides
      the gain in stability, multimerisation also leads to increased valency and allows
      the combination of several therapeutic functions. Furthermore, by expressing the
      multimers from cells, post-translational modifications could easily be
      introduced.

PMID- 16892369
TI  - Bisubstrate inhibitors of catechol O-methyltransferase (COMT): the crucial role
      of the ribose structural unit for inhibitor binding affinity.
AB  - Inhibition of the enzyme catechol O-methyltransferase offers a therapeutic handle
      to regulate the catabolism of catecholamine neurotransmitters, providing valuable
      assistance in the treatment of CNS disorders such as Parkinson's disease. A
      series of ribose-modified bisubstrate inhibitors of COMT featuring 2'-deoxy-, 3'
      deoxy-, 2'-aminodeoxy-3'-deoxy-, and 2'-deoxy-3'-aminodeoxyribose-derived central
      moieties and analogues containing the carbocyclic skeleton of the natural product
      aristeromycin were synthesized and evaluated to investigate the molecular
      recognition properties of the ribose binding site in the enzyme. Key synthetic
      intermediates in the ribose-derived series were obtained by deoxygenative [1,2]
      hydride shift rearrangement of adenosine derivatives; highlights in the synthesis
      of carbocyclic aristeromycin analogues include a diastereoselective
      cyclopropanation step and nucleobase introduction with a modified Mitsunobu
      protocol. In vitro biological evaluation and kinetic studies revealed dramatic
      effects of the ribose modification on binding affinity: 3'-deoxygenation of the
      ribose gave potent inhibitors (IC50 values in the nanomolar range), which stands
      in sharp contrast to the remarkable decrease in potency observed for 2'-deoxy
      derivatives (IC50 values in the micromolar range). Aminodeoxy analogues were only
      weakly active, whereas the change of the tetrahydrofuran skeleton to a carbocycle
      unexpectedly led to a complete loss of biological activity. These results confirm
      that the ribose structural unit of the bisubstrate inhibitors of COMT is a key
      element of molecular recognition and that modifications thereof are delicate and
      may lead to surprises.

PMID- 16892370
TI  - Synthesis and preliminary biological evaluation of 2'-substituted 2-(3'
      carboxybicyclo[1.1.1]pentyl)glycine derivatives as group I selective metabotropic
      glutamate receptor ligands.
AB  - The first series of 2'-substituted 2-(3'-carboxybicyclo[1.1.1]pentyl)glycine
      derivatives, (2R)- and (2S)-(2',2'-dichloro-3'
      carboxybicyclo[1.1.1]pentyl)glycine (10) and (11), and 2-(2'-chloro-3'
      carboxybicyclo[1.1.1]pentyl)glycine (12) were synthesized and evaluated as mGluR
      ligands. Compounds 11 and 12 were shown to be competitive group I mGluR
      antagonists. These results are also discussed in light of docking studies with
      both the active (closed) and inactive (open) conformations of mGluR1.

PMID- 16892371
TI  - Comparative analysis of the surface interaction properties of the binding sites
      of CDK2, CDK4, and ERK2.
AB  - Recently developed hydrogen-bonding and hydrophobic analysis algorithms were used
      to investigate the interaction properties of the ATP binding sites of CDK2, CDK4,
      and ERK2. We were able to prioritise those hydrogen-bonding groups that are
      observed to bind the native ATP ligand, as well as to identify other important
      groups found to bind inhibitors of these enzymes. However, as the hydrogen
      bonding groups in the ATP binding sites of these enzymes are fairly well
      conserved, we have confirmed that inhibitor selectivity may be predominantly due
      to differences in either the hydrophobic or steric properties of their binding
      sites. In particular, the hydrophobic properties of regions outside the
      specificity surface were observed to provide a rationale for the differences in
      specificity between various inhibitors to these enzymes. Our method was thus able
      to identify variations in hydrophobicity. The greater hydrophobicity of certain
      regions of CDK4 over analogous regions in CDK2 was detectable; likewise, it was
      possible to distinguish variations in hydrophobicity for regions of CDK2 against
      those in ERK2, despite the fact that these regions are largely composed of
      similar residue types.

PMID- 16892372
TI  - Phosphorothioate analogues of alkyl lysophosphatidic acid as LPA3 receptor
      selective agonists.
AB  - The metabolically stabilized LPA analogue 1-oleoyl-2-O-methyl-rac
      glycerophosphorothioate (OMPT) was recently shown to be a potent subtype
      selective agonist for LPA3, a G-protein-coupled receptor (GPCR) in the
      endothelial differentiation gene (EDG) family. Further stabilization was achieved
      by replacing the sn-1 O-acyl group with an O-alkyl ether. A new synthetic route
      for the enantiospecific synthesis of the resulting alkyl LPA phosphorothioate
      analogues is described. The pharmacological properties of the alkyl OMPT
      analogues were characterized for subtype-specific agonist activity using Ca2+
      mobilization assays in RH7777 cells expressing the individual EDG family LPA
      receptors. Alkyl OMPT analogues induced cell migration in cancer cells mediated
      through LPA1. Alkyl OMPT analogues also activated Ca2+ release through LPA2
      activation but with less potency than sn-1-oleoyl LPA. In contrast, alkyl OMPT
      analogues were potent LPA3 agonists. The alkyl OMPTs 1 and 3 induced cell
      proliferation at submicromolar concentrations in 10T 1/2 fibroblasts.
      Interestingly, the absolute configuration of the sn-2 methoxy group of the alkyl
      OMPT analogues was not recognized by any of the LPA receptors in the EDG family.
      By using a reporter gene assay for the LPA-activated nuclear transcription factor
      PPARgamma, we demonstrated that phosphorothioate diesters have agonist activity
      that is independent of their ligand properties at the LPA-activated GPCRs. The
      availability of new alkyl LPA analogues expands the scope of structure-activity
      studies and will further refine the molecular nature of ligand-receptor
      interactions for this class of GPCRs.

PMID- 16892375
TI  - Drugs targeting protein-protein interactions.
AB  - Most biological processes involve permanent and nonpermanent interactions between
      different proteins, and many protein complexes play a key role in various human
      diseases. Therefore, molecules that prevent the formation of these protein
      complexes could be valuable new therapeutic agents to treat these diseases.
      Protein interfaces have not evolved to bind low-molecular-weight molecules, as is
      the case with enzyme catalytic sites. It is therefore difficult to identify small
      compounds that inhibit protein-protein interactions. However, there is
      considerable diversity in the structure of protein interfaces, some of which may
      be more attractive than others for medicinal chemistry. One of the main
      challenges in drug discovery is to identify these interfaces and to exploit their
      properties to make marketable drugs. Herein, the properties of protein interfaces
      are discussed in light of their use as drug targets.

PMID- 16892376
TI  - Exploring metallodrug-protein interactions by ESI mass spectrometry: the reaction
      of anticancer platinum drugs with horse heart cytochrome c.

PMID- 16892377
TI  - Design, synthesis, and pharmacological characterization of polyamine toxin
      derivatives: potent ligands for the pore-forming region of AMPA receptors.
AB  - Polyamine toxins, such as philanthotoxins, are low-molecular-weight compounds
      isolated from spiders and wasps, which modulate ligand-gated ion channels in the
      nervous system. Philanthotoxins bind to the pore-forming region of AMPA
      receptors, a subtype of glutamate receptors which are important for memory
      formation and are involved in neurodegenerative diseases. Previous studies have
      demonstrated that modification of the polyamine moiety of philanthotoxins can
      lead to very potent and highly selective ligands for the AMPA receptor, as
      exemplified with philanthotoxin-56. Much less attention has been paid to the
      importance of the aromatic head group of philanthotoxins, but herein we
      demonstrate that modification of this moiety leads to a significant improvement
      in potency relative to philanthotoxin-56 at cloned AMPA receptors. Interestingly,
      the incorporation of an adamantane moiety is particularly favorable, and the most
      potent compound has a Ki value of 2 nM, making it the most potent uncompetitive
      antagonist of AMPA receptors described to date. Such compounds are potentially
      useful as neuroprotective agents.

PMID- 16892378
TI  - Old molecules for new receptors: Trp(Nps) dipeptide derivatives as vanilloid
      TRPV1 channel blockers.
AB  - The transient receptor potential vanilloid member 1 (TRPV1), an integrator of
      multiple pain-producing stimuli, is regarded nowadays as an important biological
      target for the discovery of novel analgesics. Here, we describe the first
      experimental evidence for the behavior of an old family of analgesic dipeptides,
      namely Xaa-Trp(Nps) and Trp(Nps)-Xaa (Xaa=Lys, Arg) derivatives, as potent TRPV1
      channel blockers. We also report the synthesis and biological investigation of a
      series of new conformationally restricted Trp(Nps)-dipeptide derivatives with
      improved TRPV1/NMDA selectivity. Compound 15 b, which incorporates an N-terminal
      2S-azetidine-derived Arg residue, was the most selective compound in this series.
      Collectively, a new family of TRPV1 channel blockers emerged from our results,
      although further modifications are required to fine-tune the
      potency/selectivity/toxicity balance.

PMID- 16892379
TI  - A PEG-based biocompatible block catiomer with high buffering capacity for the
      construction of polyplex micelles showing efficient gene transfer toward primary
      cells.
AB  - Nonviral gene vectors from synthetic catiomers (polyplexes) are a promising
      alternative to viral vectors. In particular, many recent efforts have been
      devoted to the construction of biocompatible polyplexes for in vivo nonviral gene
      therapy. A promising approach in this regard is the use of poly(ethylene glycol)
      (PEG)-based block catiomers, which form a nanoscaled core-shell polyplex with
      biocompatible PEG palisades. In this study, a series of PEG-based block catiomers
      with different amine functionalities were newly prepared by a simple and
      affordable synthetic procedure based on an aminolysis reaction, and their utility
      as gene carriers was investigated. This study revealed that the block catiomers
      carrying the ethylenediamine unit at the side chain are capable of efficient and
      less toxic transfection even toward primary cells, highlighting critical
      structural factors of the cationic units in the construction of polyplex-type
      gene vectors. Moreover, the availability of the polyplex micelle for transfection
      with primary osteoblasts will facilitate its use for bone regeneration in vivo
      mediated by nonviral gene transfection.

PMID- 16892380
TI  - The potential of P1 site alterations in peptidomimetic protease inhibitors as
      suggested by virtual screening and explored by the use of C-C-coupling reagents.
AB  - A synthetic concept is presented that allows the construction of peptide isostere
      libraries through polymer-supported C-acylation reactions. A phosphorane linker
      reagent is used as a carbanion equivalent; by employing MSNT as a coupling
      reagent, the C-acylation can be conducted without racemization.
      Diastereoselective reduction was effected with L-selectride. The reagent linker
      allows the preparation of a norstatine library with full variation of the
      isosteric positions including the P1 side chain that addresses the protease S1
      pocket. Therefore, the concept was employed to investigate the P1 site
      specificity of peptide isostere inhibitors systematically. The S1 pocket of
      several aspartic proteases including plasmepsin II and cathepsin D was modeled
      and docked with approximately 500 amino acid side chains. Inspired by this
      virtual screen, a P1 site mutation library was designed, synthesized, and
      screened against three aspartic proteases (plasmepsin II, HIV protease, and
      cathepsin D). The potency of norstatine inhibitors was found to depend strongly
      on the P1 substituent. Large, hydrophobic residues such as biphenyl, 4
      bromophenyl, and 4-nitrophenyl enhanced the inhibitory activity (IC50) by up to
      70-fold against plasmepsin II. In addition, P1 variation introduced significant
      selectivity, as up to 9-fold greater activity was found against plasmepsin II
      relative to human cathepsin D. The active P1 site residues did not fit into the
      crystal structure; however, molecular dynamics simulation suggested a possible
      alternative binding mode.

PMID- 16892381
TI  - Conjugation of a photosensitizer to an oligoarginine-based cell-penetrating
      peptide increases the efficacy of photodynamic therapy.
AB  - To improve the efficiency of intracellular delivery of photosensitizers and the
      efficacy of photodynamic therapy, a membrane-penetrating arginine oligopeptide
      (R7) was conjugated to 5-[4-carboxyphenyl]-10,15,20-triphenyl-2,3
      dihydroxychlorin (TPC). The resulting conjugate (R7-TPC) enhanced intracellular
      TPC uptake, which increased proportionally with the incubation time of the
      conjugate. The water solubility of the highly hydrophobic TPC photosensitizer was
      also improved after conjugation. Increased phototoxicity of R7-TPC was observed
      after an incubation time of only 30 min. Tumor cells mainly underwent apoptosis
      at lower concentrations of the photosensitizer-polyarginine conjugate, whereas
      necrotic cell damage became prevalent at higher concentrations.

PMID- 16892382
TI  - Focused libraries of 16-substituted estrone derivatives and modified e-ring
      steroids: inhibitors of 17beta-hydroxysteroid dehydrogenase type 1.
AB  - 17beta-hydroxysteroid dehydrogenase type 1 (17beta-HSD1), an oxidoreductase which
      has a preferential reductive activity using NADPH as cofactor, converts estrone
      to estradiol and is expressed in many steroidogenic tissues including breast and
      in malignant breast cells. As estradiol stimulates the growth and development of
      hormone-dependent breast cancer, inhibition of the final step of its synthesis is
      an attractive target for the treatment of this disease. The parallel synthesis of
      novel focused libraries of 16-substituted estrone derivatives and modified E-ring
      pyrazole steroids as new potent 17beta-HSD1 inhibitors is described. Substituted
      3-O-sulfamoylated estrone derivatives were used as templates and were immobilised
      on 2-chlorotrityl chloride resin to give resin-bound scaffolds with a multi
      detachable linker. Novel focused libraries of 16-substituted estrone derivatives
      and new modified E-ring steroids were assembled from these immobilised templates
      using solid-phase organic synthesis and solution-phase methodologies. Among the
      derivatives synthesised, the most potent 17beta-HSD1 inhibitors were 25 and 26
      with IC50 values in T-47D human breast cancer cells of 27 and 165 nm,
      respectively. Parallel synthesis resulting in a library of C5'-linked amides from
      the pyrazole E-ring led to the identification of 62 with an IC50 value of 700 nM.
      These potent inhibitors of 17beta-HSD1 have a 2-ethyl substituent which will
      decrease their estrogenic potential. Several novel 17beta-HSD1 inhibitors emerged
      from these libraries and these provide direction for further template exploration
      in this area. A new efficient diastereoselective synthesis of 25 has also been
      developed to facilitate supply for in vivo evaluation, and an X-ray crystal
      structure of this inhibitor is presented.

PMID- 16892383
TI  - Prenylflavonoids as nonsteroidal phytoestrogens and related structure-activity
      relationships.
AB  - In the search for estrogen receptor (ER) modulators, a series of prenylflavonoids
      were found to be widely distributed amongst tonic herbal medicines and to possess
      estrogen-like activity in MCF-7/BOS cells, as evaluated by an estrogen-screening
      assay. Cell-cycle analysis revealed that the stimulatory effects of these
      compounds toward cell proliferation were elicited at the G1-S checkpoint and
      could significantly increase the S-phase population of MCF-7 cells under hormone
      free conditions. ER-responsive gene (PS2, PgR) and protein (PgR) expression was
      also detected; mRNA and protein-expression levels for PS2 and PgR were up
      regulated by the compounds in a dose-dependent manner. These effects could be
      inhibited by the pure ER antagonist ICI 182,780 ((7alpha-[9-{4,4,5,5,5
      pentafluoropentyl}sulfinyl]nonyl)estra-1,3,5(10)-triene-3,17beta-diol). It was
      therefore concluded that the estrogen-like effects of these prenylflavonoids were
      mediated primarily through ERs. Furthermore, to explore the structure-activity
      relationship based on the estrogen receptor and detailed molecular mechanisms
      among the prenylflavonoids, protein-ligand docking simulations were carried out
      by using the DS-MODELING software package. The binding affinity of each
      prenylflavonoid toward ERalpha was scored, and the receptor-ligand interaction
      was also analyzed to provide the simulation characteristics of virtual molecular
      recognition mechanisms.

PMID- 16892386
TI  - The nuclear receptor superfamily and drug discovery.

PMID- 16892387
TI  - T4 phage photoinactivation by linear furocoumarins and angular furoquinolinones.

PMID- 16892388
TI  - Modulators of the kynurenine pathway of tryptophan metabolism: synthesis and
      preliminary biological evaluation of (S)-4-(ethylsulfonyl)benzoylalanine, a
      potent and selective kynurenine aminotransferase II (KAT II) inhibitor.

PMID- 16892389
TI  - Poly(ADP-ribose)-polymerase-catalyzed hydrolysis of NAD+: QM/MM simulation of the
      enzyme reaction.
AB  - Poly(ADP-ribose) polymerase (PARP) is a nuclear enzyme which uses NAD+ as
      substrate and catalyzes the transfer of multiple units of ADP-ribose to target
      proteins. PARP is an attractive target for the discovery of novel therapeutic
      agents and PARP inhibitors are currently evaluated for the treatment of a variety
      of pathological conditions such as brain ischemia, inflammation, and cancer.
      Herein, we use the PARP-catalyzed reaction of NAD+ hydrolysis as a model for
      gaining insight into the molecular details of the catalytic mechanism of PARP.
      The reaction has been studied in both the gas-phase and in the enzyme environment
      through a QM/MM approach. Our results indicate that the cleavage reaction of the
      nicotinamide-ribosyl bond proceeds through an SN2 dissociative mechanism via an
      oxacarbenium transition structure. These results confirm the importance of the
      structural water molecule in the active site and may constitute the basis for the
      design of transition-state-based PARP inhibitors.

PMID- 16892390
TI  - Modeling of Cdc25B dual specifity protein phosphatase inhibitors: docking of
      ligands and enzymatic inhibition mechanism.
AB  - The Cdc25 dual specificity phosphatases have central roles in coordinating
      cellular signalling processes and cell proliferation. It has been reported that
      an improper amplification or activation of these enzymes is a distinctive feature
      of a number of human cancers, including breast cancers. Thus, the inhibition of
      Cdc25 phosphatases might provide a novel approach for the discovery of new and
      selective antitumor agents. By using the crystal structure of the catalytic
      domain of Cdc25B, structural models for the interaction of various Cdc25B
      inhibitors (1-13) with the enzyme were generated by computational docking. The
      parallel use of two efficient and predictive docking programs, AutoDock and GOLD,
      allowed mutual validation of the predicted binding poses. To evaluate their
      quality, the models were validated with known structure-activity relationships
      and site-directed mutagenesis data. The results provide an improved basis for
      structure-based ligand design and suggest a possible explanation for the
      inhibition mechanism of the examined Cdc25B ligands. We suggest that the
      recurring motif of a tight interaction between the inhibitor and the two arginine
      residues, 482 and 544, is of prime importance for reversible enzyme inhibition.
      In contrast, the irreversible inhibition mechanism of 1-4 seems to be associated
      with the close vicinity of the quinone ring and the Cys473 catalytic thiolate. We
      believe that this extensive study might provide useful hints to guide the
      development of new potent Cdc25B inhibitors as novel anticancer drugs.

PMID- 16892392
TI  - Dinuclear alkylamine platinum(II) complexes of [1,2-bis(4
      fluorophenyl)ethylenediamine]platinum(II): influence of endocytosis and copper
      and organic cation transport systems on cellular uptake.
AB  - Various possible pathways for the uptake of cationic alkylamine platinum(II)
      complexes into the MCF-7 breast cancer cells were studied with di[meso-1,2-bis(4
      fluorophenyl)ethylenediamine]di[sulfinylbis(methane)-S][mu-1,6
      diaminohexaneN:N']diplatinum(II) disulfate (m-4F-PtDMSO-DAH) as an example. It
      was demonstrated that m-4F-PtDMSO-DAH competed neither for the copper transporter
      nor the organic cation transporters (OCT and OATP). Instead, adsorptive
      endocytosis by macropinocytosis played an essential role. Inhibitors of this
      processes such as amiloride, N-ethyl-N-isopropylamiloride (EIPA), wortmannin, and
      cytochalasin D decreased the intracellular uptake of m-4F-PtDMSO-DAH
      dramatically. These results support the understanding of the pharmacological
      behavior of this promising drug family, which showed no cross resistance with
      cisplatin.

PMID- 16892391
TI  - A series of unconjugated ferrocenyl phenols: prospects as anticancer agents.
AB  - We recently reported that a ferrocenyl diphenol butene derivative showed a very
      strong cytotoxic effect on both hormone-dependent and -independent breast cancer
      cell lines. In order to obtain more information about the structure-activity
      relationship in the cytotoxicity of small ferrocene compounds, we have prepared a
      series of simple unconjugated ferrocenyl diphenol complexes (ortho,para;
      meta,para; para,para). These compounds retain a reasonable to good affinity for
      both estrogen receptor types, with higher values for the beta form, and superior
      binding for the para,para diphenol complex (RBA=28%). In vitro these complexes
      exhibit significant cytotoxic effects on hormone-independent prostate (PC3) and
      breast cancer cell lines (MDA-MB231), with IC50 values between 2.5 and 4.1
      microM. This effect is more marked with PC3, the ortho,para diphenol complex
      proving the most effective. On the hormone-dependent MCF7 breast cancer cell
      line, the observed effect seems to be the result of two components, one cytotoxic
      (antiproliferative), the other estrogenic (proliferative). Electrochemical
      studies show that the cytotoxic effect of the complexes correlates with the ease
      of oxidation of the ferrocene group. All these complexes are much less cytotoxic
      than the ferrocenyl diphenol butene derivative.

PMID- 16892393
TI  - Synthesis and biological evaluation of SERMs with potent nongenomic estrogenic
      activity.
AB  - We have synthesized novel SERMs that activate a rapid response in CNS neurons,
      but which lack the ability to bind to the nuclear estrogen receptors (ERalpha and
      ERbeta). These compounds are analogues of 4-hydroxytamoxifen, but unlike 4
      hydroxytamoxifen, they do not exist as a mixture of E/Z isomers. They contain a
      carboxamide insertion between the olefin and basic phenyl side chain, which
      results in more stable geometric isomers. The amide insertion also eliminates
      their ability to bind to the nuclear estrogen receptors, and hence, they are
      unable to modulate ER-mediated gene transcription as do classical estrogens and
      SERMs. We show that one of these analogues, ST-X, elicits a potent nongenomic
      estrogen response in the CNS by rapidly inhibiting GIRK activation in
      hypothalamic gamma-aminobutyric acid (GABA) and proopiomelanocortin (POMC)
      neurons. To our knowledge, ST-X is the only SERM that modulates rapid estrogen
      responses, but which lacks nuclear ER activity.

PMID- 16892395
TI  - A novel mutation in GDF5 causes autosomal dominant symphalangism in two Chinese
      families.
AB  - Proximal symphalangism (SYM1) is an autosomal dominant disorder characterized by
      ankylosis of the proximal interphalangeal joints and fusion of carpal and tarsal
      bones. We identified and characterized two five-generation Chinese families with
      SYM1. The two families share some similarities (e.g., osseous fusion of
      interphalangeal joints of the 2-4 fingers) with SYM1 families with mutations in
      the NOG gene or the family with mutation R438L recently reported in the GDF5 gene
      (encoding a bone morphogenetic protein family member). However, they show some
      unique features including the absence of cuboid bone, the lack of shortness of
      the first and fifth metacarpal bones, and manifestation of flat feet. Genome-wide
      linkage analysis of the two families mapped the disease gene to marker D20S112
      with a combined LOD score of 4.32. Mutational analysis revealed a novel E491K
      mutation in the GDF5 gene in both families. The mutation occurs at a highly
      conserved residue in the TGF-beta domain of GDF5 and represents the second GDF5
      mutation identified for SYM1 to date. The E491K mutation co-segregated with the
      affected individuals in the two families, and did not exist in unaffected family
      members or 200 normal controls. These results indicate that defects in GDF5 can
      cause SYM1 in the Chinese population, and expand the spectrum of clinical
      phenotypes associated with mutant GDF5.

PMID- 16892397
TI  - Aquaporin water and solute channels from malaria parasites and other pathogenic
      protozoa.

PMID- 16892398
TI  - Design, synthesis, and SAR studies of mefloquine-based ligands as potential
      antituberculosis agents.

PMID- 16892399
TI  - A high-affinity carbohydrate-containing inhibitor of matrix metalloproteinases.

PMID- 16892400
TI  - Detection of overexpressed COX-2 in precancerous lesions of hamster pancreas and
      lungs by molecular imaging: implications for early diagnosis and prevention.
AB  - The enzyme cyclooxygenase-2 (COX-2) is overexpressed in many cancers,
      cardiovascular disease, neurodegenerative disorders, and arthritis. Selective
      inhibitors of COX-2 have been developed as therapeutics or preventive agents for
      these diseases. However, recent reports have revealed a significant increase in
      cardiovascular mortality in long-term users of the COX-2 inhibitors Vioxx and
      Celebrex, emphasizing the need for noninvasive tests that allow the
      identification of individuals whose COX-2 levels are overexpressed prior to
      assignment to treatment with these drugs. In this study, we have prepared a
      radioiodinated analogue of the selective COX-2 inhibitor celecoxib, and verified
      its binding to the COX-2 enzyme in vitro. Biodistribution studies in hamsters
      demonstrated significantly higher levels of radiotracer in animals treated with
      the tobacco carcinogen NNK in lung, pancreas, and liver. Assessment of COX-2
      levels by whole-body planar nuclear imaging two hours after injection of the
      radiotracer was suggestive of a distinct increase in COX-2 in the pancreas and
      liver of a hamster treated for 10 weeks with NNK, in the lungs and liver of a
      second animal, and in the liver only, in two additional animals from the same
      treatment group. Immunostains showed selective overexpression of COX-2 in pre
      neoplastic lesions of the pancreas and lungs in only those animals that showed
      tracer accumulation in these organs and in the livers of all NNK-treated
      hamsters. Immunostains for COX-1 yielded detectable reactions in the intestinal
      epithelium but not in pancreas, lungs, or liver, supporting the specificity of
      the tracer for COX-2. Our data provide proof of principle for the hypothesis that
      molecular imaging with radiolabeled COX-2 inhibitors can be used for the
      noninvasive monitoring of overexpressed COX-2 levels.

PMID- 16892402
TI  - In silico classification of HERG channel blockers: a knowledge-based strategy.
AB  - The blockage of the hERG potassium channel by a wide number of diverse compounds
      has become a major pharmacological safety concern as it can lead to sudden
      cardiac death. In silico models can be potent tools to screen out potential hERG
      blockers as early as possible during the drug-discovery process. In this study,
      predictive models developed using the recursive partitioning method and created
      using diverse datasets from 203 molecules tested on the hERG channel are
      described. The first model was built with hERG compounds grouped into two
      classes, with a separation limit set at an IC50 value of 1 microm, and reaches an
      overall accuracy of 81%. The misclassification of molecules having a range of
      activity between 1 and 10 microM led to the generation of a tri-class model able
      to correctly classify high, moderate, and weak hERG blockers with an overall
      accuracy of 90%. Another model, constructed with the high and weak hERG-blocker
      categories, successfully increases the accuracy to 96%. The results reported
      herein indicate that a combination of precise, knowledge management resources and
      powerful modeling tools are invaluable to assessing potential cardiotoxic side
      effects related to hERG blockage.

PMID- 16892401
TI  - A fluorine scan at the catalytic center of thrombin: C--F, C--OH, and C--OMe
      bioisosterism and fluorine effects on pKa and log D values.
AB  - A series of 16 tricyclic thrombin inhibitors was prepared by using the 1,3
      dipolar cycloaddition of azomethine ylides derived from 3- or 4-hydroxyproline
      and 4-bromobenzaldehyde, with N-(4-fluorobenzyl)maleimide as the key step. The
      terminal pyrrolidine ring of the inhibitors was systematically substituted to
      explore the potential bioisosteric behavior of C-F, C-OH, and C-OMe residues
      pointing into the environment of the catalytic center of a serine protease. X-ray
      crystal structure analyses revealed a distinct puckering preference of this ring.
      Substitution by F, HO, and MeO has a strong effect on the basicity of the
      adjacent pyrrolidine nitrogen center which originates from two sigma-inductive
      pathways between this center and the electronegative O and F atoms. gem
      Difluorination decreases the pKa value of this tertiary amine center to <2,
      making the conjugated ammonium ion a moderately strong acid. Unexpectedly, F
      substitution next to the nitrogen center reduced the lipophilicity of the
      ligands, as revealed by measurements of the logarithmic partition coefficient log
      D. The biological assays showed that all compounds are thrombin inhibitors with
      activities between Ki=0.08 and 2.17 microM. Bioisosteric behavior of F, HO, and
      MeO substituents was observed. Their electronegative F and O atoms undergo
      energetically similar polar interactions with positively polarized centers, such
      as the N atom of His 57 which is hydrogen bonded to the catalytic Ser 195.
      However, for energetically similar polar interactions of C-F, C-OH, and C-OMe to
      occur, sufficient space is necessary for the accommodation of the Me group of the
      C-OMe residue, and a H-bond acceptor must be present to prevent unfavorable
      desolvation of the C-OH residue.

PMID- 16892404
TI  - Enzyme isoselective inhibitors: application to drug design.
AB  - Common methodologies of computer-assisted drug design focus on noncovalent enzyme
      ligand interactions. We introduced enzyme isoselective inhibition trend analysis
      as a tool for the expert analysis of covalent reversible inhibitors. The
      methodology is applied to predict the binding affinities of a series of
      transition-state analogue inhibitors of medicinally important serine and cysteine
      hydrolases. These inhibitors are isoselective: they have identical noncovalent
      recognition fragments (RS) and different reactive chemical fragments (CS).
      Furthermore, it is possible to predict the binding affinities of a series of
      isoselective inhibitors toward a prototype enzyme and to extrapolate the data to
      a target medicinally important enzyme of the same family. Rational design of CS
      fragments followed by conventional RS optimization could be used as a novel
      approach to drug design.

PMID- 16892403
TI  - Enzyme isoselective inhibitors: a tool for binding-trend analysis.
AB  - A transition-state analogue inhibitor that covalently reversibly binds to an
      enzyme formally consists of two parts: the chemical site, CS and the recognition
      site, RS. We have experimentally and theoretically demonstrated that the trend of
      binding affinity in a series of isoselective inhibitors (with identical RS and
      different CS fragments) depends mainly on their CS fragments. Isoselective
      inhibitors have the same affinity trend toward different enzymes of the same
      family with a common catalytic mechanism. Thus, very good correlation between
      experimentally determined and theoretically calculated Ki values was
      demonstrated. A practical outcome is the application of the described method as a
      tool for an expert analysis in virtual screening of inhibitor libraries and in
      the design of new enzyme inhibitors.

PMID- 16892405
TI  - Synthesis and cytotoxicity of enantiomerically pure [1,2-diamino-1-(4
      fluorophenyl)-3-methylbutane]platinum(II) complexes.
AB  - A series of leaving group derivatives of enantiomerically pure [1,2-diamino-1-(4
      fluorophenyl)-3-methylbutane]platinum(II) complexes were synthesized and tested
      for cytotoxicity. The enantiomeric purity was determined by 1H NMR spectroscopy
      on the final diamines after derivation with (1R)-myrtenal. For coordination to
      platinum, the diamines were reacted with K2PtI4. The treatment of
      diiodoplatinum(II) complexes (4F-Ph/iProp-PtI2) with Ag2SO4 resulted in the
      sulfatoplatinum(II) complexes (4F-Ph/iProp-PtSO4), which can be easily
      transformed to dichloroplatinum(II) complexes (4F-Ph/iProp-PtCl2) with 2 n HCl.
      The importance of the leaving groups and the configuration at the diamine ligand
      on the antiproliferative effects was evaluated on the hormone-dependent MCF-7 and
      the hormone-independent MDA-MB 231 breast cancer cell lines as well as the
      LNCaP/FGC prostate cancer cell line. (R,R)-4F-Ph/iProp-PtCl2 was identified as
      the most active platinum(II) complex. The 3-methyl group increased
      antiproliferative effects relative to the [1,2-diamino-1-(4
      fluorophenyl)butane]platinum(II) complexes described in an earlier study.

PMID- 16892407
TI  - Anophthalmia-esophageal atresia syndrome caused by an SOX2 gene deletion in
      monozygotic twin brothers with markedly discordant phenotypes.
AB  - The clinical combination of anophthalmia/microphthalmia and esophageal atresia
      was first recognized in 1988 as a distinct variable multi-system malformation
      syndrome and since then at least 17 cases of the disease have been described, all
      of them sporadic in occurrence. We report a heterozygous SOX2 gene mutation
      underlying the syndrome of anophthalmia/microphthalmia-esophageal atresia and
      demonstrate that this entity can be associated to considerable clinical
      variability as shown by the discordant ocular phenotype observed in monozygotic
      twin brothers carrying an SOX2 deletion. This is the first report describing a
      strikingly discordant eye phenotype in monozygotic twins with the condition, with
      one of our patients being the first reported individual carrying an SOX2 lesion
      associated with unilateral eye defect. We discuss the probable sources for this
      remarkable phenotypic heterogeneity of the anophthalmia/microphthalmia syndrome
      in individuals with an identical genetic constitution.

PMID- 16892409
TI  - Determination of the sexual phenotype in a child with 45,X/46,X,Idic(Yp)
      mosaicism: importance of the relative proportion of the 45,X line in gonadal
      tissue.
AB  - We report on a girl who, despite her 45,X/46,X,der(Y) karyotype, showed no signs
      of virilization or physical signs of the Ullrich-Turner syndrome (UTS), except
      for a reduced growth rate. After prophylactic gonadectomy due to the risk of
      developing gonadoblastoma, the gonads and peripheral blood samples were analyzed
      by fluorescence in situ hybridization (FISH) and polymerase chain reaction (PCR)
      to detect Y-specific sequences. These analyses allowed us to characterize the Y
      derived chromosome as being an isodicentric Yp chromosome (idic(Yp)) and showed a
      pronounced difference in the distribution of the 45,X/46,X,idic(Yp) mosaicism
      between the two analyzed tissues. It was shown that, although in peripheral blood
      almost all cells (97.5%) belonged to the idic(Yp) line with a duplicated SRY
      gene, this did not determine any degree of male sexual differentiation in the
      patient, as in the gonads the predominant cell line was 45,X (60%).

PMID- 16892408
TI  - Contiguous hemizygous deletion of TBX5, TBX3, and RBM19 resulting in a combined
      phenotype of Holt-Oram and ulnar-mammary syndromes.

PMID- 16892410
TI  - SALL1 mutations in sporadic Townes-Brocks syndrome are of predominantly paternal
      origin without obvious paternal age effect.
AB  - Autosomal dominant Townes-Brocks syndrome (TBS) is characterized by imperforate
      anus, triphalangeal and supernumerary thumbs, dysplastic ears and sensorineural
      hearing loss, and may also involve other organ systems. Strong inter- and
      intrafamiliar variability is known. Approximately 50% of TBS cases are sporadic
      and due to de novo mutations in the SALL1 gene. SALL1 encodes a zinc finger
      protein operating as a transcriptional repressor and localizing to
      pericentromeric heterochromatin. We traced the parental origin of SALL1 mutations
      in sporadic TBS by analysis of linkage between SALL1 mutations and exonic or
      intronic polymorphisms in 16 families with 10 different mutations. Mutations were
      of paternal origin in 14 of 16 cases (87.5%). Paternal origin was independent of
      the mutation type. The mean paternal age at conception was 29.9 and the mean
      maternal age 26.5 years. We conclude that de novo mutations in SALL1 mostly occur
      on the paternally derived chromosome 16 without an obvious age effect.

PMID- 16892411
TI  - Killing of a pearl-spotted owlet (Glaucidium perlatum) by male red colobus
      monkeys (Procolobus tephrosceles) in a forest fragment near Kibale National Park,
      Uganda.
AB  - Adult male red colobus (Procolobus tephrosceles) were observed capturing and
      killing an owl (Glaucidium perlatum) in the Rurama forest fragment near Kibale
      National Park in western Uganda. The owl was not subsequently eaten by the
      colobus, their conspecifics, or the other primates present during the attack.
      Because the incident was preceded by an agonistic encounter with a raptor, the
      event is best interpreted as a misdirected antipredator behavior. Although
      antipredator behaviors are not unknown in red colobus, this is the first such
      incident directed against a raptor to be documented.

PMID- 16892412
TI  - Conflict management by hamadryas baboons (Papio hamadryas hamadryas) during
      crowding: a tension-reduction strategy.
AB  - Primates change a variety of behavioral responses during short-term exposure to
      crowding. Under crowded conditions, rates of aggression, submissive behavior, and
      affiliative behavior may increase or decrease. Different patterns of change among
      these three categories of response have been interpreted as various coping
      "strategies" for managing the increased risk of conflict under crowded
      conditions. Grooming is of particular interest because this behavior is known to
      have a calming influence on the recipient and could be used to manage conflict
      under tense situations. A captive group of nine hamadryas baboons (Papio
      hamadryas hamadryas) composed of two harems was observed under short-term
      crowding to determine whether this species adopts conflict-management strategies
      similar to those described in other primates. The aggression, submission,
      affiliation, and displacement activities of the six adults in the group (two
      males and four females) were recorded, and behaviors in their small indoor
      quarters was compared with baseline behaviors in the outdoor section of their
      enclosure, which had over 10 times more space. Repeated-measures analysis of
      variance (ANOVA) was used to compare behavioral rates during crowding with
      baseline rates recorded immediately after crowding and during matched controls
      collected at the same time of day as the crowding sessions. Aggression and
      submission rates did not change significantly across conditions. Huddling
      together and proximity increased during crowding, and females increased grooming
      of their harem male during crowding. Displacement activities (e.g., pacing and
      self-grooming) increased during crowding, but scratching, an indicator of anxiety
      in primates, did not. The pattern of behavior exhibited by this group conforms to
      an active "tension-reduction" strategy in which animals successfully reduce the
      higher risk of aggression during crowding.

PMID- 16892413
TI  - Histology of the sternal and suprapubic skin areas in lion tamarins
      (Leontopithecus sp. Callitrichidae-primates).
AB  - Though knowledge regarding the biology and morphology of lion tamarins is scarce
      in the literature, it is very important for their conservation. This paper
      focuses on the anatomical and histological aspects of the glands involved in the
      scent-marking behavior of lion tamarins. It examines the histological aspects of
      sternal and suprapubic skin sections of specimens that were preserved in
      formaldehyde and were the property of the Rio de Janeiro Primatology Center
      Museum. Eighteen specimens from three lion tamarin (Leontopithecus sp.) species
      (L. rosalia, L. chrysomelas, and L. chrysopygus) were analyzed. Both sexes were
      represented, and macroscopic hypertrophy was quantified by direct observation of
      the tegument on the sternal area and classified as discrete, moderate, or
      accentuated for each specimen. The skin of both sexes had a high degree of
      histological resemblance to that of other primates, including humans. The
      epidermis presented stratified squamous keratinous epithelia, with a few cellular
      layers and dermis with cutaneous appendages (i.e., hair follicles and both
      sebaceous and sweat glands). The dermal papillae were short, and the sebaceous
      and apocrine sweat glands resembled those of humans. These glands were present in
      the dermis of the analyzed skin fragments of both sternal and suprapubic regions
      in great numbers. Furthermore, we were able to establish a relationship between
      the macroscopic appearance of the sternal tegument and the degree of microscopic
      gland hyperplasia.

PMID- 16892414
TI  - Rescue behavior in white-faced capuchin monkeys during an intergroup attack:
      support for the infanticide avoidance hypothesis.
AB  - In this work we report the first published observational evidence of rescue
      behavior during an intergroup interaction in white-faced capuchin monkeys (Cebus
      capucinus). The study groups (groups AA and RR) inhabit the forest of Lomas
      Barbudal Biological Reserve in Guanacaste, Costa Rica, and have been under
      investigation since 1990 and 1997, respectively. Here we report a single
      interaction in which a victim mother-infant pair was rescued from potential
      injury or death by the intervention of an adult male from their social group
      during an intergroup encounter. We discuss several hypotheses that may be
      relevant in explaining this unique observation.

PMID- 16892415
TI  - Substrate optimization in nut cracking by capuchin monkeys (Cebus apella).
AB  - We conducted an experiment to examine the effect of substrate on the nut-cracking
      behavior of a group of semicaptive capuchin monkeys. We wanted to determine
      whether tufted capuchin monkeys were selective in choosing the substrate on which
      they pound nuts, and whether the choice of substrate affected the outcome. Eight
      adult females and eight juveniles were provided with nuts in the outdoor
      facility. We found that 1) all adult females and three young capuchins succeeded
      in cracking nuts; 2) they preferred the hardest substrates (concrete and stone);
      3) there is a link between the substrate and the amount of time needed to crack a
      nut; 4) most young capuchins used various substrates, some of which were
      inadequate, in a haphazard manner; and 5) there are different forms of nut
      cracking. We conclude that adult capuchins choose the hardest substrates, and
      that these substrates support efficient cracking.

PMID- 16892416
TI  - Highly polymorphic STR marker amplified with human DYS389 primers in Japanese
      macaques (Macaca fuscata).
AB  - Amplification products from male and female Japanese macaques were obtained by
      PCR with human Y-chromosomal DYS389 primers. These products were examined by
      electrophoresis and sequence analysis. The PCR products from the 12 Japanese
      macaques tested had different band patterns on an electrophoretogram. Sequence
      analysis of the products revealed that the high polymorphism originated from
      variable numbers of repeats of two separate CTAT sequences. The sequences of the
      Japanese macaque products were similar to those of the reference human DYS389
      sequence. However, variable CTGT repeats and a difference in the second forward
      primer binding site yielded two products in human males, DYS389I and DYS389II,
      which do not exist in Japanese macaques. Our results suggest that the human
      DYS389 primers may be a potential tool not only for distinguishing between human
      and Japanese macaque DNA samples, but also for identifying individual macaques,
      because of the highly polymorphic alleles.

PMID- 16892417
TI  - Factor analysis of the Yale-Brown Obsessive Compulsive Scale in a family study of
      obsessive-compulsive disorder.
AB  - Our objective in this study was to determine whether symptoms of obsessive
      compulsive disorder (OCD) cluster into groups that can usefully subclassify OCD.
      Psychiatrists or psychologists interviewed 221 subjects using the Lifetime
      Anxiety Version of the Schedule for Affective Disorders and Schizophrenia (SADS
      LA) for the diagnosis of DSM-IV disorders, and the Yale-Brown Obsessive
      Compulsive Scale (Y-BOCS) for OCD symptoms. We analyzed 16 symptom categories
      from the Y-BOCS using exploratory factor analysis to identify latent symptom
      dimensions. The relationship between these symptom dimensions and clinical
      characteristics and familiality was investigated. A four-factor model emerged as
      the best classification of OCD symptoms in the Y-BOCS. These factors were labeled
      Pure Obsessions, Contamination, Symmetry/Order, and Hoarding. The contamination
      factor was least likely to be associated with other Axis I disorders. Whereas no
      significant relationship was found between the factor scores of probands and the
      presence of OCD in their first-degree relatives, the Symmetry/Order and Hoarding
      factors did breed true. Hoarding was found to predict poorer treatment response.
      A four-factor classification of OCD features best describes the symptom patterns
      of a sample of patients with OCD. There were specific clinical correlates for
      these factors, and significant intrafamilial sib-sib correlations were found for
      the Symmetry/Order and Hoarding factors.

PMID- 16892418
TI  - Screening for PTSD in public-sector mental health settings: the diagnostic
      utility of the PTSD checklist.
AB  - There are few available data on how to accurately screen for and assess
      posttraumatic stress disorder (PTSD) among severely mentally ill adults, a group
      with high rates of unrecognized trauma and PTSD symptoms. We examined the
      diagnostic utility of a widely used screening instrument, the PTSD Checklist
      (PCL), for diagnosing PTSD among 44 traumatized, adult, public-sector mental
      health patients recruited through a community mental health program. Participants
      completed the PCL and the Clinician-Administered PTSD Scale (CAPS), which is
      considered the "gold standard" for determining PTSD diagnoses. Data provide
      preliminary support for the use of the PCL as a screening instrument in public
      psychiatric settings, indicating that the optimal cut-point for adults with
      severe mental illness is about 54 (with slightly higher or lower recommended cut
      points depending on the clinical context and purpose of the PCL). Such data are
      critical to ensuring that public-sector mental health patients with trauma
      related difficulties are identified and referred for appropriate services.

PMID- 16892419
TI  - A controlled trial of paroxetine for chronic PTSD, dissociation, and
      interpersonal problems in mostly minority adults.
AB  - This study evaluated the efficacy of paroxetine for symptoms and associated
      features of chronic posttraumatic stress disorder (PTSD), interpersonal problems,
      and dissociative symptoms in an urban population of mostly minority adults. Adult
      outpatients with a primary DSM-IV diagnosis of chronic PTSD received 1 week of
      single-blind placebo (N = 70). Those not rated as significantly improved were
      then randomly assigned to placebo (N = 27) or paroxetine (N = 25) for 10 weeks,
      with a flexible dosage design (maximum 60 mg by week 7). Significantly more
      patients treated with paroxetine were rated as responders (14/21, 66.7%) on the
      Clinical Global Impression-Improvement Scale (CGI-I) compared to patients treated
      with placebo (6/22, 27.3%). Mixed effects models showed greater reductions on the
      Clinician-Administered PTSD Scale (CAPS) total score (primary plus associated
      features of PTSD) in the paroxetine versus placebo groups. Paroxetine was also
      superior to placebo on reduction of dissociative symptoms [Dissociative
      Experiences Scale (DES) score] and reduction in self-reported interpersonal
      problems [Inventory of Interpersonal Problems (IIP) score]. In a 12-week
      maintenance phase, paroxetine response continued to improve, but placebo response
      did not. Paroxetine was well tolerated and superior to placebo in ameliorating
      the symptoms of chronic PTSD, associated features of PTSD, dissociative symptoms,
      and interpersonal problems in the first trial conducted primarily in minority
      adults.

PMID- 16892421
TI  - Regional differences in architecture and mineralization of developing mandibular
      bone.
AB  - The goal of this study was to investigate the mutual relationship between
      architecture and mineralization during early development of the pig mandible.
      These factors are considered to define the balance between the requirements for
      bone growth on the one hand and for load bearing on the other. Architecture and
      mineralization were examined using micro-CT, whereas the mineral composition was
      assessed spectrophotometrically in groups of fetal and newborn pigs. The
      development of the condyle coincided with a reorganization of bone elements
      without an increase in bone volume fraction, but with an increase in
      mineralization and a change in mineral composition. In the corpus, the bone
      volume fraction and mineralization increased simultaneously with a restructuring
      of the bone elements and a change in mineral composition. The growth of the
      condyle was reflected by regional differences in architecture and mineralization.
      The anterior and inferior regions were characterized by a more dense bone
      structure and a higher mineralization as compared to posterior and superior
      regions, respectively. In the corpus, growth was mainly indicated by differences
      between buccal and lingual plates as well as between anterior, middle, and
      posterior regions characterized by a more compact structure and higher
      mineralization in the lingual and middle regions. In conclusion, the architecture
      and mineralization in the condyle and corpus started to deviate early during
      development toward their destiny as trabecular and cortical bone, respectively.
      These results were compatible with those obtained with mineral composition
      analysis. Regional differences within condyle and corpus reflected known
      developmental growth directions.

PMID- 16892422
TI  - Increased eNOS accounts for changes in connexin expression in renal arterioles
      during diabetes.
AB  - Previous studies have shown that connexin (Cx) expression is considerably higher
      in the preglomerular compared to postglomerular vasculature and that these
      differences are accentuated during diabetes. Since nitric oxide (NO) has been
      reported to alter Cx expression in endothelial cells and muscle cells and NO
      bioavailability is altered in diabetes, we hypothesized that NO may be
      responsible for the changes during diabetes. Cx expression was studied using
      immunohistochemistry in mice in which eNOS expression was either upregulated
      (eNOS transgenic) or downregulated (eNOS knockout). Diabetes was induced
      intraperitoneally with a single dose of alloxan or multiple low doses of
      streptozotocin. Expression of Cx40 in smooth muscle cells of afferent arterioles
      was increased, while expression of Cx43 in endothelial cells of efferent
      arterioles was absent in eNOS transgenic mice, similar to the changes occurring
      in wild-type mice during diabetes. Expression of Cx40 and Cx43 in eNOS knockout
      mice was not different from control; however, induction of diabetes in eNOS
      knockout mice failed to produce any changes in Cx40 or Cx43 in either afferent or
      efferent arterioles. Immunohistochemistry showed that eNOS expression was
      increased in the endothelium of renal arterioles in wild-type diabetic and eNOS
      transgenic mice, but absent from arterioles of eNOS knockout mice. We conclude
      that changes occurring in Cx expression in afferent and efferent arterioles
      during diabetes may result from increased eNOS.

PMID- 16892420
TI  - Resilience: research evidence and conceptual considerations for posttraumatic
      stress disorder.
AB  - The growing recognition and occurrence of traumatic exposure in the general
      population has given increased salience to the need to understand the concept of
      resilience. More than just the "flip side" of a risk factor, the notion of
      resilience encompasses psychological and biological characteristics, intrinsic to
      an individual, that might be modifiable and that confer protection against the
      development of psychopathology in the face of stress. In this review, we provide
      some perspective on the concept of "resilience" by examining early use of the
      term in research on "children at risk" and discuss the relationship between risk
      and resilience factors. We then review psychological and biological factors that
      may confer resilience to the development of posttraumatic stress disorder (PTSD)
      following trauma, examine how resilience has been assessed and measured, and
      discuss issues to be addressed in furthering our understanding of this critical
      concept going forward.

PMID- 16892423
TI  - Tryptamine induces cell death with ultrastructural features of autophagy in
      neurons and glia: Possible relevance for neurodegenerative disorders.
AB  - Tryptamine derivatives are a family of biogenic amines that have been suggested
      to be modulators of brain function at physiological concentrations. However,
      pharmacological concentrations of these amines display amphetamine-like
      properties, and they seem to play a role in brain disorders. Amphetamines induce
      autophagy in nerve cells, and this type of cell death has also been involved in
      neurodegenerative diseases. In the present work, we clearly demonstrate for the
      very first time that high concentrations of tryptamine (0.1-1 mM) induce
      autophagy in HT22 and SK-N-SH nerve cell lines and in primary cultures of
      astrocytes, glial cells being less sensitive than neurons. Ultrastructural cell
      morphology shows all of the typical hallmarks of autophagy. There is no nuclear
      chromatin condensation, endoplasmic reticulum and mitochondria are swollen, and a
      great number of double-membraned autophagosomes and residual bodies can be shown
      in the cytoplasm. Autophagosomes and residual bodies contain mitochondria,
      membranes, and vesicles and remain unabridged until the cell membrane is
      disrupted and the cell dies. The same results have been found when cells were
      incubated with high concentrations of 5-methoxytryptamine (0.1-1 mM). Our results
      establish a possible link between the role of tryptamine derivatives in brain
      disorders and the presence of autophagic cell death in these kinds of disorders.

PMID- 16892424
TI  - Cardiac outflow tract: a review of some embryogenetic aspects of the conotruncal
      region of the heart.
AB  - A review concerning some embryogenetic aspects of the cardiac outflow tract is
      presented. Two main topics are discussed: the truncal septation and the secondary
      heart field. In the context of the septation of the truncus arteriosus, the
      development of the arterial valves is largely discussed, particularly in
      reference to the sinuses of Valsalva. Emphasis is also given to the fate of the
      external myocardial wall of the truncus arteriosus, as this primordial myocardial
      surface disappears later in the development. Molecular genetics data concerning
      Sox4 and NF-Atc transcription factors are correlated in the present review with
      rare forms of truncus malformations encountered in human pathology. The roles
      exerted by the secondary heart field and the neural crest on the development and
      growth of the conotruncal musculature are largely discussed. Reported
      experimental ablations of both secondary heart field and neural crest, showed
      conotruncal defects such as persistent truncus arteriosus, tetralogy of Fallot,
      and double-outlet right ventricle, which were considered as the result of a short
      outflow tract causing, ultimately, a lack of conotruncal rotation. In this
      regard, some morphologic correlations are carried out, in the present review,
      between these experimental animal models and human malformations, and it is
      thought that this sort of conotruncal defects cannot be explained always in terms
      of conotruncal hypoplasia. Finally, influence of Pitx2c, a left-right laterality
      signaling gene, on the modulation of the conotruncal rotation, as most recently
      reported, is emphasized in terms of very likely multifactorial contributions in
      the embryogenesis of the conotruncal region of the heart.

PMID- 16892425
TI  - General organization of the perinatal and adult accessory olfactory bulb in mice.
AB  - The vomeronasal system is currently a topical issue since the dual functional
      specificity, vomeronasal system-pheromones, has recently been questioned.
      Irrespective of the tools used to put such specificity in doubt, the diversity of
      the anatomy of the system itself in the animal kingdom is probably of more
      importance than has previously been considered. It has to be pointed out that a
      true vomeronasal system is integrated by the vomeronasal organ, the accessory
      olfactory bulb, and the so-called vomeronasal amygdala. Therefore, it seems
      reasonable to establish the corresponding differences between a well-developed
      vomeronasal system and other areas of the nasal cavity in which putative
      olfactory receptors, perhaps present in other kinds of mammals, may be able to
      detect pheromones and to process them. In consequence, a solid pattern for one
      such system in one particular species needs to be chosen. Here we report on an
      analysis of the general morphological characteristics of the accessory olfactory
      bulb in mice, a species commonly used in the study of the vomeronasal system,
      during growth and in adults. Our results indicate that the critical period for
      the formation of this structure comprises the stages between the first and the
      fifth day after birth, when the stratification of the bulb, the peculiarities of
      each type of cell, and the final building of glomeruli are completed. In
      addition, our data suggest that the conventional plexiform layers of the main
      olfactory bulb are not present in the accessory bulb.

PMID- 16892426
TI  - Vascular patterning of the quail coronary system during development.
AB  - Recent studies have provided insights into specific events that contribute to
      vasculogenesis and angiogenesis in the developing coronary vasculature. This
      study focused on the developmental progression of coronary vascularization
      beginning with tube formation and ending with the establishment of a coronary
      arterial tree. We used electron microscopy, histology of serial sections, and
      immunohistochemistry in order to provide a comprehensive view of coronary vessel
      formation during the embryonic and fetal periods of the quail heart, a species
      that has been used in a number of studies addressing myocardial vascularization.
      Our data reveal features of progenitor cells and blood islands, tubular
      formation, and the anatomical relationship of a transformed periarterial tubular
      network and sympathetic ganglia to the emergence and branching of the right and
      left coronary arteries. We have traced the pattern of coronary artery branching
      and documented its innervation. Finally, our data include the relationship of
      fibronectin, laminin, and apoptosis to coronary artery growth. Our findings bring
      together morphological events that occur over the embryonic and fetal periods and
      provide a baseline for studies into the mechanisms that regulate the various
      events that occur during these time periods.

PMID- 16892427
TI  - Vascular localization and proliferation in the growing tip of the deer antler.
AB  - The process of angiogenesis is of interest because of the significant clinical
      benefits associated with controlling vascular growth. Within the antler,
      chondrogenesis and antler elongation are occurring at the rate of 1-2 cm per day
      and thus blood vessels are growing at this same rapid pace. We demonstrate that
      the process of angiogenesis in the antler is controlled at various tissue
      locations. The findings clearly differentiate the spatial location of the stem
      cells that drive chondrogenesis from the proliferation process driving the
      angiogenesis. Vessels within the lateral dermis contained BrdU-positive cells,
      suggesting that these vessels were elongating. Within the precartilage region,
      proliferating vessels were detected in bundles of complex structure evenly
      distributed throughout this tissue layer. The support cells within these bundles
      of vessels were detected by staining with alpha-smooth muscle actin, while the
      endothelial cells were negative. Additionally, the alpha-smooth muscle actin
      staining was found in association with the cartilage cells of the antler. The
      marked proliferation of the vascular associated cells in the precartilage region
      identified this area as a major region of vascular growth in the antler. We
      propose that within the precartilage region, the most likely mechanisms to
      explain the observed vascular morphology are that of vascular extension of the
      existing vessels and intussusceptive angiogenesis or sprouting to generate the
      small bundles of vessels. Wiley-Liss, Inc.

PMID- 16892428
TI  - Direct thrombin inhibition appears to be a safe and effective anticoagulant for
      percutaneous bypass graft interventions.
AB  - BACKGROUND: Percutaneous coronary interventions (PCI) of coronary artery bypass
      grafts (CABG) are associated with worse outcomes compared with those of native
      coronary PCI. Little is known concerning the use of direct thrombin inhibition
      during CABG intervention. The objective of this report is to examine the safety
      and efficacy of bivalirudin with GPIIb/IIIa blockade inhibition in patients
      undergoing CABG PCI. GP IIb/IIIa use was provisional in REPLACE-2 and planned in
      REPLACE-1. METHODS AND RESULTS: A post hoc analysis of patients undergoing CABG
      PCI in the REPLACE-1 and -2 trials was performed. In REPLACE-1, patients were
      randomized to either heparin or bivalirudin, with GP IIb/IIIa inhibitor use at
      the operator's discretion. In REPLACE-2, patients were randomized to heparin plus
      GP IIb/IIIa inhibition versus bivalirudin with provisional GP IIb/IIIa blockade.
      In both studies, randomized treatment groups were well matched. In unadjusted and
      logistic regression analysis, there were no significant differences in the
      combined endpoint of death, myocardial infarction, urgent revascularization, or
      major bleeding when patients were treated with either heparin or bivalirudin.
      Individual safety and efficacy endpoints were also similar. Minor bleeding was
      significantly reduced in patients treated with bivalirudin (14.8% vs. 22.7%, P =
      0.037). Follow-up data available from the REPLACE-2 trial at 12 months found
      similar efficacy between groups with a trend towards decreased 12 month mortality
      in the bivalirudin vs. heparin groups (4.2% vs. 7.8%, P = 0.16). CONCLUSION: CABG
      PCI using bivalirudin with provisional GPIIb/IIIa inhibition appears to provide
      similar safety and efficacy to heparin with GPIIb/IIIa inhibition.

PMID- 16892429
TI  - Motor unit number estimation predicts disease onset and survival in a transgenic
      mouse model of amyotrophic lateral sclerosis.
AB  - Motor unit number estimation (MUNE) has proved useful in predicting rate of
      progression and survival in patients with amyotrophic lateral sclerosis (ALS). In
      animal models, it has demonstrated physiological effects of experimental
      medications that were not evident behaviorally. We sought to determine more
      specifically what aspects of function and survival that MUNE could predict in the
      G93A transgenic mouse model of ALS. Transgenic mice were examined in two distinct
      treatment studies, neither of which showed an effect of drug on survival,
      behavioral measures, or MUNE. MUNE was performed using a modification of the
      incremental stimulation method by stimulating the sciatic nerve at the sciatic
      notch, and recording with a circumferential surface electrode around the
      ipsilateral distal hindlimb. Both limbs were studied and the results averaged.
      MUNE was performed longitudinally on all animals from near onset to premorbid
      state. Each study was evaluated separately. For both studies, MUNE at initial
      study correlated significantly with behavioral determination of disease onset,
      and MUNE slope from initial to final study correlated significantly with disease
      duration, as measured from onset to time of death. However, the final MUNE value
      did not correlate with survival. Thus, in two studies involving animals with
      quite different disease courses, initial MUNE effectively predicted symptom onset
      and MUNE slope predicted survival. This suggests that MUNE has potential efficacy
      as a useful functional outcome measure in both animal and human studies of ALS.

PMID- 16892430
TI  - High-repetition cyclic loading is a risk factor for a lumbar disorder.
AB  - Epidemiological data suggest that prolonged exposure to cyclic lumbar flexion
      elicits a chronic neuromuscular disorder and disability in workers. This study
      provides a physiological and biomechanical assessment of various repetitions of
      cyclic lumbar flexion sessions as a risk factor for development of an acute
      neuromuscular disorder. An in vivo feline model was subjected to 10 minutes of
      cyclic (0.25-HZ) loading, followed by a 10-minute rest period, repeated three
      times in one experimental group, six times in a second group, and nine times in
      the third group, followed by rest for 7 hours. Displacement of the lumbar
      viscoelastic tissue and reflex electromyographic (EMG) activity from the lumbar
      multifidus muscle were monitored. Creep developed and accumulated during each
      load/rest period and partially recovered during the subsequent rest. Loading
      periods were characterized by a decrease in reflex EMG activity with superimposed
      spasms. In the 7-hour recovery period, initial hyperexcitability was present in
      all groups, whereas only the six- and nine-repetition groups displayed
      significant delayed hyperexcitability, indicating the presence of acute
      inflammation. The mathematical model developed fit the data reasonably well, as
      the R2 values were generally near 0.90. It was concluded that the resulting
      delayed muscular hyperexcitability constitutes an acute neuromuscular disorder
      associated with exposure to many repetitions of cyclic lumbar flexion. The acute
      disorder can become chronic if not allowed sufficient rest to resolve itself.
      Workers engaged in cyclic lumbar flexion (e.g., loading/unloading, assembly
      workers) should avoid long-term exposure in order to prevent the development of a
      chronic neuromuscular condition known as cumulative trauma disorder.

PMID- 16892431
TI  - Prevalence of unfavorable angiographic characteristics for percutaneous
      intervention in patients with unprotected left main coronary artery disease.
AB  - OBJECTIVES: The goal of this study was to determine the proportion of patients
      with left main coronary disease (LMCD) with unfavorable characteristics for
      percutaneous coronary intervention (PCI). BACKGROUND: Published series suggest
      that LMCD can be treated percutaneously, however, the proportion of patients in
      whom PCI is an option based on angiographic criteria is unknown. METHODS: In
      13,228 consecutive coronary angiograms, 476 (3.6%) patients had < or =60%
      stenosis of the left main. In 232 patients with unprotected LMCD, the clinical
      characteristics and angiograms were reviewed with six features chosen as
      "unfavorable" for PCI: (1) Bifurcation LMCD, (2) occlusion of a major coronary,
      (3) ejection fraction <30%, (4) occlusion of a dominant RCA, (5) left dominant
      circulation, and (6) coexisting three-vessel disease. Treatment modality and 1
      year mortality were determined. RESULTS: The mean age was 69 years and 68% were
      male. Unfavorable characteristics were common with at least one unfavorable
      characteristic seen in 80%. Bifurcation disease was the most common unfavorable
      characteristic observed (53%) and coexisting three-vessel disease was seen in
      38%. Treatment consisted of CABG in 205 (88%), medical therapy in 24 (10%) and
      PCI in 3 (1%). Among patients referred for CABG, 1 year survival was 88% with
      similar rates of survival for those with favorable characteristics (86%) compared
      to those with at least one unfavorable characteristic (88%). CONCLUSIONS: Most
      patients with LMCD have at least one unfavorable characteristic for PCI
      suggesting that PCI may be a technically difficult option for most patients with
      LMCD.

PMID- 16892432
TI  - A modified balloon crush approach improves side branch access and side branch
      stent apposition during crush stenting of coronary bifurcation lesions.
AB  - OBJECTIVES: Despite the advent of drug eluting stents and newer interventional
      techniques designed to treat the main vessel and side branch in bifurcation
      stenoses, optimal treatment of the side branch remains problematic. We aimed to
      assess the feasibility of a modified balloon crush technique for percutaneous
      treatment of coronary bifurcation stenoses. BACKGROUND: Use of the crush
      technique in bifurcation stenoses remains limited by access to the side branch
      after main vessel stent deployment, as well as limitations of side branch stent
      deployment. The modified balloon crush technique aims to improve side branch
      access and stent apposition. METHODS: The modified balloon crush is similar to
      the previously described balloon crush technique. Following side branch stent
      deployment, a balloon positioned in the main vessel is deployed to crush the
      proximal side branch stent. A guide wire is then placed into the side branch with
      a subsequent high-pressure balloon inflation at the side branch ostium. This
      opens the stent struts at the ostium of the side branch, facilitating future
      passage of the guide wire following main vessel stent deployment, prior to
      kissing balloon inflation. RESULTS: We performed this modification of the crush
      technique safely in 10 patients. We were successful in obtaining side branch
      access in nine of ten patients following initial main vessel stent deployment. In
      the only failure, there was a 90 degrees angle between the main vessel and side
      branch. CONCLUSIONS: The modified balloon crush technique can be safely
      performed, while optimizing side branch access and side branch stent apposition.

PMID- 16892433
TI  - A randomized, double-blind, placebo-controlled, multicenter, pilot study of the
      safety and feasibility of catheter-based intramyocardial injection of AdVEGF121
      in patients with refractory advanced coronary artery disease.
AB  - BACKGROUND: The experience with direct myocardial injection of adenovirus
      encoding angiogenic growth factor is limited to invasive surgical approach.
      Accordingly, we sought to evaluate, for the first time, in a randomized, double
      blind, placebo-controlled, phase I pilot study the safety and feasibility of
      percutaneous catheter-based intramyocardial delivery of a replication-deficient
      adenovector encoding the 121-amino-acid isoform of vascular endothelial growth
      factor (AdVEGF121). METHODS: Ten "no-option" patients with severe coronary artery
      disease were randomized (2:1) to receive AdVEGF121 (4 x 10(10) pu) or placebo as
      fifteen 100 microL, evenly distributed, endomyocardial injections using a
      nonflouroscopic, 3-dimensional mapping and injection (NOGA) catheter-based
      system. RESULTS: Injection procedure was successfully completed in all cases and
      was associated with no major adverse events. AdVEGF121 was considered potentially
      associated with a single serious adverse event of transient moderate fever.
      Elevated postprocedure CK and CK-MB fraction levels were recorded in two placebo
      treated and three AdVEGF121-treated patients; all CK measured values were <1.5
      times upper limit of normal. All adenoviral cultures (urine and throat swab) were
      negative 24-hr after dosing, and no significant changes in serial plasma VEGF
      levels were noted over time. At 12 months follow-up, no cancers, proliferative
      retinal changes, or significant abnormalities in hepatic, renal or hematological
      indices were observed. CONCLUSIONS: Percutaneous, catheter-based AdVEGF121
      intramyocardial injection is a practical, feasible, and potentially safe approach
      for intramyocardial gene transfer. A larger randomized, phase II efficacy study
      is warranted.

PMID- 16892434
TI  - Pivotal, randomized U.S. study of the Symbiottrade mark covered stent system in
      patients with saphenous vein graft disease: eight-month angiographic and clinical
      results from the Symbiot III trial.
AB  - OBJECTIVES: The purpose of this study was to evaluate the clinical and
      angiographic outcomes of the Symbiot ePTFE covered stent versus bare metal stents
      (BMS) for the treatment of saphenous vein graft (SVG) disease. BACKGROUND: The
      Symbiot stent was developed to reduce periprocedural complications, by
      potentially preventing distal embolization, and to serve as a possible barrier to
      cell migration, thus reducing restenosis. METHODS: Symbiot III is a prospective,
      randomized trial of 400 patients at 45 US sites, with 201 patients in the Symbiot
      group and 199 in the BMS group. Randomization was stratified based on the
      intended use of embolic protection devices and glycoprotein IIb/IIIa inhibitors.
      The primary endpoint was percent diameter stenosis (%DS) as measured by
      quantitative coronary angiography at 8 months. Secondary endpoints included MACE
      (cardiac death, MI, TVR). RESULTS: The groups were well matched for all baseline
      clinical and lesion characteristics. At 8 months, %DS was comparable between
      groups (30.9% Symbiot, 31.9% BMS, P = 0.80). Although the rates of binary
      restenosis in the stented segment were similar (29.1% Symbiot, 21.9% BMS, P =
      0.17), more patients in the Symbiot group had binary restenosis at the proximal
      edge (9.0% Symbiot, 1.8% BMS, P = 0.0211). There was no difference in the
      incidence of MACE between groups (30.6% Symbiot, 26.6% BMS, P = 0.43).
      CONCLUSIONS: This study failed to show an advantage for the Symbiot stent in the
      treatment of degenerated SVGs. This PTFE covered stent does not appear to act as
      a barrier to prevent restenosis.

PMID- 16892435
TI  - Subcutaneous administration of nitroglycerin to facilitate radial artery
      cannulation.
AB  - OBJECTIVES: To study the effect of sublingual versus subcutaneous nitroglycerin
      on radial artery spasm caused by failed access attempts. BACKGROUND: Radial
      artery spasm is the leading reason for failed radial access. We studied the
      efficacy of systemic versus local nitroglycerin in relieving radial artery spasm
      caused by needle entry resulting in failed cannulation. METHODS: Fifty-two
      consecutive patients were studied. All patients had failed attempt at radial
      artery cannulation, resulting in loss of radial pulse. Patients were divided in
      three groups, group I (n = 11), observed without additional treatment, group II
      (n = 20), administered 400 mcg of sublingual nitroglycerin, and group III (n =
      21), administered 400 mcg of subcutaneous nitroglycerin at the site of the lost
      radial pulse. All patients were monitored for the return of radial pulse.
      Demographics, hemodynamics, and time to return of radial pulse as well as ability
      to successfully cannulate the radial artery were recorded. RESULTS: Seventy-two
      percent of group I patients, 90% of group II patients, and 100% of group III
      patients had re-establishment of radial pulse. The time to return of radial pulse
      was significantly shorter for group III compared with that for group II (3 +/- 1
      min vs. 8 +/- 1 min respectively, P < 0.001). Re-establishment of radial pulse
      was faster in group II and group III compared with that in group I (18 +/- 5 min,
      P < 0.001). Systolic blood pressure changes and headaches were less common in
      group III. CONCLUSION: Subcutaneous administration of nitroglycerin is superior
      in facilitating radial artery cannulation after initial failed attempt.

PMID- 16892437
TI  - Acute coronary artery thrombosis and a giant coronary artery aneurysm: an
      atypical combination and an unconventional catheter-based intervention.
AB  - Coronary artery aneurysm is an unusual finding at coronary arteriography. We
      present a case of acute myocardial infarction and a giant aneurysm of the left
      circumflex coronary artery (CX) in a 70-year-old male with hypertension. The
      culprit lesion was a thrombus occupying the aneurysm and the distal CX. By an
      unconventional manoeuvre the thrombus was aspirated via the 7 French guiding
      catheter. After stent implantation in the distal CX a thrombolysis in myocardial
      infarction 3 flow was achieved and still present at 2-month follow-up. The
      patient was prescribed aspirin and clopidogrel as a life-long therapy.

PMID- 16892436
TI  - Improved survival with drug-eluting stent implantation in comparison with bare
      metal stent in patients with severe left ventricular dysfunction.
AB  - OBJECTIVE: We examined the efficacy of drug-eluting stent (DES) implantation
      (Sirolimus or Paclitaxel) in patients with ischemic cardiomyopathy and severe
      left ventricular (LV) dysfunction and compared the outcome with a similar group
      of patients undergoing bare metal stent (BMS) implantation. BACKGROUND: Patients
      with severe LV dysfunction are a high risk group. DES may improve the long term
      outcomes compared with BMS. METHODS: One hundred and ninety one patients (23%
      women) with severe LV dysfunction (LV ejection fraction < or =35%) underwent
      coronary stent implantation between May 2002 and May 2005 and were available for
      follow-up. One hundred and twenty eight patients received DES (Sirolimus in 72
      and Paclitaxel in 54) and 63 patients had BMS. Patients with acute S-T elevation
      myocardial infarction (STEMI) were excluded. The primary endpoint was
      cardiovascular mortality. A composite endpoint of major adverse cardiac events
      (MACE) including cardiovascular mortality, myocardial infarction (MI), and target
      vessel revascularization (TVR) was the secondary endpoint. RESULTS: Mean follow
      up was 420 +/- 271 days. No differences were noted in age (69 +/- 10 years vs. 70
      +/- 10 years, P = NS), number of vessel disease (2.3 +/- 0.7 vs. 2.2 +/- 0.8, P =
      NS), history of congestive heart failure (47% vs. 46%, P = NS), MI (60% vs. 61%,
      P = NS), or number of treated vessels (1.3 +/- 0.5 vs. 1.3 +/- 0.6, P = NS) for
      the DES and BMS group, respectively. Diabetes was more common among DES patients
      (45% vs. 25%, P = 0.01). The left ventricular ejection fraction (LVEF) was
      similar between the two groups (28% +/- 6% vs. 26% +/- 8%, P = NS for the DES and
      BMS, respectively). During the follow-up, there were a total of 25 deaths of
      which two were cancer related (2 in DES group). There were 23 cardiac deaths,
      8/126 (6%) which occurred in the DES group and 15/63 (24%) in the BMS group (P =
      0.05 by log-rank test). MACE rate was 10% for the DES group and 41% for the BMS
      group (P = 0.003). NYHA class improved in both groups (from 2.5 +/- 0.8 to 1.7 +/
      0.8 in DES and from 2 +/- 0.8 to 1.4 +/- 0.7 in the BMS, P = NS). CONCLUSION:
      Compared with bare-metal stents, DES implantation reduces mortality and MACE in
      high risk patients with severe left ventricular dysfunction.

PMID- 16892438
TI  - Acute thrombosis of a coronary artery aneurysm: toughing it out with the poor
      man's thrombectomy catheter technique.

PMID- 16892439
TI  - Very late [corrected] thrombosis of a sirolimus-eluting stent.
AB  - We report the case of a 67-year-old man who presented with a [corrected] non-ST
      elevation acute myocardial infarction 41 months after implantation of a sirolimus
      eluting stent in his left circumflex coronary artery. Coronary angiography
      revealed stent thrombosis.

PMID- 16892440
TI  - Stent-assisted detachable coil embolization of pseudoaneurysms in the coronary
      circulation.
AB  - Pseudoaneurysms in the coronary circulation are an uncommon occurrence that can
      develop spontaneously in the setting of atherosclerosis or can develop after
      catheter-based coronary interventions. The natural history, clinical outcome, and
      optimal therapy for pseudoaneurysms in the coronary circulation are not clearly
      established. Recent advances in the techniques and technologies used for
      endovascular treatment of intracranial aneurysms may be applicable to the
      management of coronary aneurysms and pseudoaneurysms. We present a case of
      spontaneous coronary pseudoaneurysm formation after paclitaxel drug-eluting stent
      implantation and a case of pseudoaneurysm formation in a saphenous vein graft
      that were both successfully treated with stent-assisted detachable coil
      embolization.

PMID- 16892441
TI  - Comparison of transendocardial and retrograde coronary venous intramyocardial
      catheter delivery systems in healthy and infarcted pigs.
AB  - We compared two routes for myocardial delivery of therapeutics, transendocardial
      (TE) delivery with an intramyocardial injection catheter, and retrograde coronary
      venous (RCV) delivery with a balloon occlusion catheter in the interventricular
      vein. METHODS: TE and RCV injection of 15 microM, neutron-activatable
      microspheres was compared in healthy pigs (Group I, n = 3), pigs with a 1-week
      old myocardial infarction (MI; group II, n = 5), and pigs with a 2-weeks-old MI
      (group III, n = 4). The MI was induced by a 1-hr balloon occlusion in the LAD.
      Both methods were compared in the same animal using different microspheres. The
      RCV catheter allowed for continuous measurement of distal pressure and 2.5 x
      10(6) microspheres were injected in 10 ml at 300 mmHg above balloon occlusion
      pressure. The TE injections were targeted to the infarct zone and 2.5 x 10(6)
      microspheres were distributed over 10 injections of 200 microl. RESULTS: The
      retention of microspheres decreased with increase in MI age, but was comparable
      between devices within the groups. RCV delivery resulted in (14.3 +/- 0.9)%
      microsphere retention in Group I, (10.3 +/- 0.2)% in Group II, and (6.4 +/- 0.1)%
      in group III (P < 0.05 versus group I). Microsphere retention after TE was (15.1
      +/- 0.7)% in group I, (18.9 +/- 0.6)% in group II, (4.1 +/- 0.1)% in Group III (P
      < 0.05 versus groups I and II). The RCV catheter delivered primarily to
      midventricular, antero-septal segments, whereas TE targeted apical areas
      predominantly. CONCLUSIONS: Delivery efficacy was comparable between devices in
      each group however RCV targeted midventricular areas whereas TE targeted apical
      areas.

PMID- 16892442
TI  - Synchronous carotid stenting and cardiac surgery: an initial single-center
      experience.
AB  - Concurrent severe carotid and cardiac disease is a challenging situation where
      staged surgery is probably the most common strategy, although it is still
      controversial. We report in-hospital and midterm outcome of 30 patients who
      received carotid stenting and synchronous cardiac surgery. All received carotid
      stenting under aspirin and regular unfractioned heparin (UFH) and were
      immediately transferred to the operating room for coronary and/or cardiac valve
      surgery. All patients received aspirin and clopidogrel once bleeding was ruled
      out, after surgery. In-hospital complications were: three surgical related
      deaths, one TIA, and no patient suffered stroke or myocardial infarction.
      Hospital stay was 14 +/- 11.8 days. Survivors were followed for 18.4 +/- 14
      months. There were two non-related deaths, but no stroke nor cardiac or carotid
      reinterventions. In conclusion, this small series showed that synchronous carotid
      stenting and cardiac surgery was feasible with an acceptable complication rate in
      a high-surgical-risk population which could not undergo staged procedures.

PMID- 16892443
TI  - Usefulness of translesional pressure gradient and pharmacological provocation for
      the assessment of intermediate renal artery disease.
AB  - OBJECTIVE: We sought to determine the hemodynamic significance of intermediate
      RAS by measuring translesional systolic pressure gradients (TSPG), using a
      pressure-sensing guidewire at baseline and after acetylcholine (ACh) induced
      hyperemia, following selective renal artery angiography. BACKGROUND: Renal artery
      stenosis (RAS) is a cause of reversible hypertension and nephropathy. Stenting
      effectively relieves RAS, however improvement in blood pressure control or renal
      function is variable and unpredictable. Hemodynamic significance is usually
      present with RAS when diameter stenosis is >75%, but is less predictable in
      intermediate (30%-75%) RAS. METHODS: Twenty-two patients (26 renal arteries) with
      uncontrolled hypertension underwent invasive hemodynamic assessment because of
      intermediate RAS, defined as radiocontrast angiographic diameter stenosis (DS)
      between 30% and 75% (quantitative DS was measured prospectively). Translesional
      pressure gradients were measured using a 0.014" pressure-sensing wire. Hyperemia
      was induced by administration of intrarenal ACh. RESULTS: Visual and measured
      angiographic lesion severity did not correlate with TSPG either at baseline
      (visual DS, R(2) = 0.091, P = 0.13; measured DS, R(2) = 0.124, P = 0.07) or with
      hyperemia (visual DS, R(2) = 0.057, P = 0.24; measured DS, R(2) = 0.101, P =
      0.12). Baseline and maximal hyperemic gradient did correlate (R(2) = 0.567; P <
      0.05). Pharmacological provocation produced a significant increase in TSPG (mean;
      baseline, 18 +/- 21 vs. hyperemia, 34 +/- 41 mm Hg; P < 0.05). A hemodynamically
      significant lesion (TSPG > 20 mm Hg) was found in 14/26 (54%) arteries (13
      patients); 13 (60%) patients subsequently underwent renal artery stenting for
      hemodynamically significant RAS. At follow-up (at least 30 days), there was a
      significant decrease in systolic blood pressure (mean; 167 +/- 24 vs. 134 +/- 19
      mm Hg; P < 0.001). CONCLUSIONS: Intrarenal administration of ACh induces
      hyperemia and can be used to unmask resistive renal artery lesions. Gradient
      measurement and induced hyperemia may be warranted in the invasive assessment of
      intermediate renal artery stenoses, rather than relying on stenosis severity
      alone. Further study is needed to determine whether translesional pressure
      gradients and pharmacological provocation predict clinical benefit after renal
      artery stenting.

PMID- 16892444
TI  - Percutaneous ex-vivo femoral arterial bypass: a novel approach for treatment of
      acute limb ischemia as a complication of femoral arterial catheterization.
AB  - This report describes the use of a percutaneous ex-vivo femoral arterial bypass
      in three patients with acute lower extremity ischemia that occurred as a
      complication of femoral artery catheterization. Utilizing standard equipment and
      techniques, a percutaneous ex-vivo femoral artery bypass can restore antegrade
      flow to the ischemic limb in patients with impaired aorto-iliac inflow
      circulation, which may arise from iatrogenic dissection or the need for large in
      dwelling sheaths required for hemodynamic support. This technique is considered a
      temporizing measure when conventional therapies are not possible. Contrast
      angiography is recommended to localize and define the cause of limb ischemia, and
      to permit safe placement of vascular sheaths in the "donor and recipient"
      arteries.

PMID- 16892446
TI  - The role of BMS in the drug eluting stent era: is still there any place for them?

PMID- 16892445
TI  - Vascular ultrasound imaging to study immediate postcatheterization vascular
      complications in children.
AB  - Vascular occlusion is the major complication of percutaneous cardiac
      catheterization in children. This is a prospective study to evaluate post
      catheterization vascular complications in 120 consecutive children with the help
      of vascular ultrasound and Doppler imaging. Ultrasound imaging of both iliac and
      femoral veins and arteries was done one hour prior and 24 hours after cardiac
      catheterization. Patients with prior thrombus or occlusion of femoral/iliac vein
      or artery due to previous cardiac catheterization were excluded from the study.
      Age of the patients ranged from 22 days to 12 years with a mean of 56 months and
      weight ranged from 3 to 57 kg with a mean of 14.3 kg. Procedure time was less
      than 60 minutes in 74 patients (61.66%) and more than 60 minutes in 46 patients
      (38.33%). 4F sized arterial sheath was used in 108 patients. 5F or bigger sized
      arterial sheath was used in remaining 12 patients. Incidence of arterial
      occlusion was higher in patients weighing less than 10 kg (16%) as compared with
      patients weighing more than 10 kg (5.5%) {P = 0.031}. Arterial thrombosis was
      more in infants (16%) as compared with older children (7%) {P = 0.203} Prolonged
      procedure time or use of larger sized sheath did not have higher incidence of
      arterial occlusion. Venous thrombosis was found in 2 patients (1.66%) who had 5F
      venous sheath. One patient had arterio venous fistula. Our study shows vascular
      ultrasound imaging can provide anatomical details of femoral and iliac vessels
      and is a easier and accurate method of assessing post-catheterization vascular
      complications in children.

PMID- 16892447
TI  - PICS/ENTICHS 2006. Abstracts of Pediatric and Adult Interventional Therapies for
      Congenital and Valvular Heart Disease, September 10-13, 2006, Las Vegas, Nevada,
      USA.

PMID- 16892448
TI  - Avoiding misclassification bias with the traditional Charnley classification:
      rationale for a fourth Charnley class BB.
AB  - Long-term follow up of patients with total hip arthroplasty (THA) revealed a
      marked deterioration of walking capacities in Charnley class B after
      postoperative year 4. We hypothesized that a specific group of patients, namely
      those with unilateral hip arthroplasty and an untreated but affected
      contralateral hip was responsible for this observation. Therefore, we conducted a
      study taking into consideration the two subclasses that make up Charnley class B:
      patients with unilateral THA and contralateral hip disease and patients with
      bilateral THA. A sample of 15,160 patients with 35,773 follow ups that were
      prospectively collected over 10 years was evaluated. The sample was categorized
      into four classes according to a new modified Charnley classification. Annual
      analyses of the proportion of patients with ambulation longer than 60 min were
      conducted. The traditionally labeled Charnley class B consists of two very
      different patient groups with respect to their walking capacities. Those with
      unilateral THA and contralateral hip disease have underaverage walking capacities
      and a deterioration of ambulation beginning 3 to 4 years after surgery. Those
      with bilateral THA have stable overaverage walking capacities similar to Charnley
      class A. An extension of the traditional Charnley classification is proposed,
      taking into account the two different patient groups in Charnley class B. The new
      fourth Charnley class consists of patients with bilateral THA and was labeled BB
      in order to express the presence of two artificial hip joints and to preserve the
      traditional classification A through C.

PMID- 16892449
TI  - Subthalamic nucleus deep brain stimulation: summary and meta-analysis of
      outcomes.
AB  - Subthalamic nucleus (STN) deep brain stimulation (DBS) is currently the most
      common therapeutic surgical procedure for patients with Parkinson's disease (PD)
      who have failed medical management. However, a recent summary of clinical
      evidence on the effectiveness of STN DBS is lacking. We report the results of
      such a systematic review and meta-analysis. A comprehensive review of the
      literature using Medline and Ovid databases from 1993 until 2004 was conducted.
      Estimates of change in absolute Unified Parkinson's Disease Rating Scale (UPDRS)
      scores after surgery were generated using random-effects models. Sources of
      heterogeneity were explored with meta-regression models, and the possibility of
      publication bias was evaluated. Patient demographics, reduction in medication
      requirements, change in dyskinesia, daily offs, quality of life, and a ratio of
      postoperative improvement from stimulation compared to preoperative improvement
      by medication from each study were tabulated and average scores were calculated.
      Adverse effects from each study were summarized. Thirty-seven cohorts were
      included in the review. Twenty-two studies with estimates of standard errors were
      included in the meta-analysis. The estimated decreases in absolute UPDRS II
      (activities of daily living) and III (motor) scores after surgery in the
      stimulation ON/medication off state compared to preoperative medication off state
      were 13.35 (95% CI: 10.85-15.85; 50%) and 27.55 (95% CI: 24.23-30.87; 52%),
      respectively. Average reduction in L-dopa equivalents following surgery was 55.9%
      (95% CI: 50%-61.8%). Average reduction in dyskinesia following surgery was 69.1%
      (95% CI: 62.0%-76.2%). Average reduction in daily off periods was 68.2% (95% CI:
      57.6%-78.9%). Average improvement in quality of life using PDQ-39 was 34.5% +/-
      15.3%. Univariable regression showed improvements in UPDRS III scores were
      significantly greater in studies with higher baseline UPDRS III off scores,
      increasing disease duration prior to surgery, earlier year of publication, and
      higher baseline L-dopa responsiveness. Average baseline UPDRS III off scores were
      significantly lower (i.e., suggesting milder disease) in later than in earlier
      studies. In multivariable regression, L-dopa responsiveness, higher baseline
      motor scores, and disease duration were independent predictors of greater change
      in motor score. No evidence of publication bias in the available literature was
      found. The most common serious adverse event related to surgery was intracranial
      hemorrhage in 3.9% of patients. Psychiatric sequelae were common. Synthesis of
      the available literature indicates that STN DBS improves motor activity and
      activities of daily living in advanced PD. Differences between available studies
      likely reflect differences in patient populations and follow-up periods. These
      data provide an estimate of the magnitude of the treatment effects and emphasize
      the need for controlled and randomized studies.

PMID- 16892450
TI  - Parapsychology on the couch: the psychology of occult belief in Germany, c. 1870
      1939.
AB  - This article considers the attempts of academic psychologists and critical
      occultists in Germany during the late nineteenth and early twentieth centuries to
      construct a psychology of occult belief. While they claimed that the purpose of
      this new subdiscipline was to help evaluate the work of occult researchers, the
      emergence of a psychology of occult belief in Germany served primarily to
      pathologize parapsychology and its practitioners. Not to be outdone, however,
      parapsychologists argued that their adversaries suffered from a morbid inability
      to accept the reality of the paranormal. Unable to resolve through experimental
      means the dispute over who should be allowed to mold the public's understanding
      of the occult, both sides resorted to defaming their opponent.

PMID- 16892451
TI  - The effect of aminoguanidine against cholestatic liver injury in rats.
AB  - We investigated the protective role of aminoguanidine (AG) in rat liver injury
      induced by chronic biliary obstruction. Secondary biliary cirrhosis was induced
      by bile duct ligation for 14 days. Swiss albino rats were divided into three
      groups: Common bile duct ligated (CBDL) rats; Group A, CBDL rats treated with AG
      as Group B and simple laparotomy group known as the Sham group; Group C. Group B
      received 200 mg/kg of AG intraperitoneally daily throughout 14 days. The present
      data showed decreased gama glutamyl transferase (GGT), aspartate aminotransferase
      (AST), bilirubin and alanine aminotransferase (ALT) levels in the AG treated
      rats, when compared with CBDL rats (p < 0.05). In the AG treated rats, tissue
      levels of malondialdehyde (MDA) were significantly lower than that in CBDL rats
      (p < 0.001). Although the levels of glutathione (GSH) in AG treated rats were
      higher and myeloperoxidase (MPO) were lower than that in CBDL rats, the
      difference was not statistically significant (p > 0.05). The levels of
      interleukin-1alpha (IL-1alpha) and tumor necrosis factor-alpha (TNF-alpha) were
      significantly lower and although the levels of interleukin-6 (IL-6) were lower in
      AG treated rats than that in CBDL rats, the difference was not statistically
      significant. Administration of AG in the rats with biliary obstruction resulted
      in inhibition of ductular proliferation and portal inflammation. The present
      study demonstrates that intraperitoneal administration of AG in CBDL rats
      maintains antioxidant defenses, reduces liver oxidative and cytokine damage and
      ductular proliferation and portal inflammation. This effect of AG may be useful
      in the preservation of liver injury in cholestasis.

PMID- 16892452
TI  - Hexosamine induction of oxidative stress, hypertrophy and laminin expression in
      renal mesangial cells: effect of the anti-oxidant alpha-lipoic acid.
AB  - We have previously shown that one of the potential mediators of the deleterious
      effects of high glucose on extracellular matrix protein (ECM) expression in renal
      mesangial cells is its metabolic flux through the hexosamine biosynthesis pathway
      (HBP). Here, we investigate further whether the hexosamines induce oxidative
      stress, cell-cycle arrest and ECM expression using SV-40-transformed rat
      mesangial (MES) cells and whether the anti-oxidant alpha-lipoic acid will reverse
      some of these effects. Culturing renal MES cells with high glucose (HG, 25 mM) or
      glucosamine (GlcN, 1.5 mM) for 48 h stimulates laminin gamma1 subunit expression
      significantly approximately 1.5 +/- 0.2- and 1.9 +/- 0.3-fold, respectively, when
      compared to low glucose (LG, 5 mM). Similarly, HG and GlcN increase the level of
      G0/G1 cell-cycle progression factor cyclin D1 significantly approximately 1.7 +/-
      0.2- and 1.4 +/- 0.04-fold, respectively, versus LG (p < 0.01 for both).
      Azaserine, an inhibitor of glutamine:fruc-6-PO(4) amidotransferase (GFAT) in the
      HBP, blocks the HG-induced expression of laminin gamma1 and cyclin D1, but not
      GlcN's effect because it exerts its metabolic function distal to GFAT. HG and
      GlcN also elevate reactive oxygen species (ROS) generation, pro-apoptotic caspase
      3 activity, and lead to mesangial cell death as revealed by TUNEL and Live/Dead
      assays. FACS analysis of cell-cycle progression shows that the cells are arrested
      at G1 phase; however, they undergo cell growth and hypertrophy as the RNA/DNA
      ratio is significantly (p < 0.05) increased in HG or GlcN-treated cells relative
      to LG. The anti-oxidant alpha-lipoic acid (150 microM) reverses ROS generation
      and mesangial cell death induced by HG and GlcN. Alpha-lipoic acid also reduces
      HG and GlcN-induced laminin gamma1 and cyclin D1 expression in MES cells. In
      addition, induction of diabetes in rats by streptozotocin (STZ) increases both
      laminin gamma1 and cyclin D1 expression in the renal cortex and treatment of the
      diabetic rats with alpha-lipoic acid (400 mg kg(-1) body weight) reduces the
      level of both proteins significantly (p < 0.05) when compared to untreated
      diabetic rats. These results support the hypothesis that the hexosamine pathway
      mediates mesangial cell oxidative stress, ECM expression and apoptosis. Anti
      oxidant alpha-lipoic acid reverses the effects of high glucose, hexosamine and
      diabetes on oxidative stress and ECM expression in mesangial cells and rat
      kidney.

PMID- 16892453
TI  - Lipid peroxidation in ovariectomized and pinealectomized rats: the effects of
      estradiol and progesterone supplementation.
AB  - In the present study, we investigated the effect of estradiol and progesterone
      supplementation on oxidant and antioxidant parameters of renal tissue in
      ovariectomized and pinealectomized rats. The study was carried out on 36 adult,
      Sprague-Dawley strain female rats, 6 months of age and weighing 200-250 g. The
      rats were divided into six groups, each group included six rats: Group 1: Sham
      ovariectomized (Sham-Ovx); Group 2: Ovariectomized (Ovx); Group 3: Ovx and
      estradiol (E) and progesterone (P) supplemented (Ovx+E-P); Group 4:
      Ovariectomized and sham pinealectomy (Ovx+sham Pnx); Group 5:
      Ovariectomized+Pinealectomized (Ovx+Pnx); Group 6:
      Ovariectomized+Pinealectomized+Hormone Supplemented group (Ovx+Pnx+E-P). The
      levels of malondialdehyde (MDA), reduced glutathione (GSH) and glutathione
      peroxidase (GSH-Px) were analysed in renal tissues of rats. The highest and the
      lowest levels of MDA were determined in Groups 5 and 1 respectively (p < 0.001).
      However, GSH and GSH-Px levels demonstrated statistically important decreases in
      groups 2, 4, 5 (p < 0.001). The findings of this study demonstrate that
      ovariectomy leads to oxidative damage in renal tissue. Pinealectomy in addition
      to ovariectomy greatly increases the oxidative damage. However, female sex
      hormones supplementations to the Ovx and/or Ovx+Pnx rats protected against lipid
      peroxidation by activating the antioxidant system.

PMID- 16892454
TI  - Vanadyl sulfate protects against streptozotocin-induced morphological and
      biochemical changes in rat aorta.
AB  - The aim of this study was to investigate the protective effects of vanadyl
      sulfate on aorta tissue of normal and streptozotocin (STZ)-induced diabetic rats,
      morphologically and biochemically. The animals were made diabetic by an
      intraperitoneal injection of streptozotocin (65 mg/kg) and vanadyl sulfate (100
      mg/kg) that was given every day for 60 days by gavage technique to rats. Under
      the light and transmission electron microscopes, hypertrophy of the vessel wall,
      focal disruption in the elastic lamellae, an increase in thickness of total
      aortic wall, tunica intima, subendothelial space and adventitial layer, and a
      disorganization in smooth muscular cells of the tunica media were observed in
      diabetic animals. The aorta lipid peroxidation (LPO) levels were significantly
      increased and the aorta glutathione (GSH) levels were significantly reduced in
      STZ diabetic rats. In diabetic rats administered vanadyl sulfate for 60 days,
      aorta LPO levels significantly decreased and the aorta GSH level significantly
      increased. In conclusion, in vivo treatment with vanadyl sulfate of diabetic rats
      prevented the morphological and biochemical changes observed in thoracic aorta of
      diabetic animals.

PMID- 16892455
TI  - Human soluble E-selectin immunoadhesin inhibits leukemic monocyte adhesion to
      endothelial cells.
AB  - Immunoadhesins are immunoglobulin (Ig)-like chimeric proteins comprised of target
      binding regions fused to the Fc-hinge region of Ig, and are designed to have a
      long half-life and antibody-like properties. In an effort to find a good
      candidate for therapeutic use for inflammatory responses, we constructed a
      soluble human E-selectin immunoadhesin containing the extracellular region of
      human E-selectin fused to the Fc-hinge region of human IgG, and determined its
      effects on leukocyte adhesion and rolling in vitro. Our results revealed that the
      adhesion of leukocytes to endothelial cells was efficiently inhibited in the
      presence of 50 nM E-selectin immunoadhesin. In addition, the E-selectin
      immunoadhesin significantly inhibited leukocyte rolling on endothelial cells in
      perfusion experiments performed at 1.0 dyne/cm(2) wall shear stress. These
      findings indicate that our E-selectin immunoadhesin decreases leukocyte
      attachment and rolling in vitro, suggesting that this immunoadhesin may be a
      promising candidate for therapeutic anti-inflammatory use.

PMID- 16892456
TI  - Evaluation of DNA vaccination with recombinant adenoviruses using bioluminescence
      imaging of antigen expression: impact of application routes and delivery with
      dendritic cells.
AB  - Recombinant DNA vaccines are able to induce strong CD8+ T cell mediated immunity
      and have become increasingly attractive for the prevention and treatment of
      infectious diseases and cancer. Dendritic cells (DC), which critically control
      cellular immune responses, have been transduced with antigen ex vivo and used as
      'nature's adjuvant' to enhance vaccine efficacy. The impact of the application
      route on the in vivo distribution of antigen and the stimulation of CD8+ T cells
      have been subjects of considerable debate. Here we report the construction of
      vectors expressing a fusion protein between EGFP, the H2-K(b)-binding peptide
      OVA(aa257-264) and green click beetle luciferase as a model antigen which allows
      for simultaneous quantitative assessment of antigen expression using fluorescence
      and bioluminescence imaging in correlation with CD8+ T cell stimulation in vivo.
      We applied this construct to evaluate DNA vaccination with recombinant adenoviral
      vectors, assess the impact of using cultured DC for vaccine delivery and
      investigate different application routes. Antigen expression was non-invasively
      followed in vivo by visualizing bioluminescence with an ultrasensitive CCD
      camera. CD8+ T cell stimulation was detected with H2-K(b)-OVA(aa257-264)
      tetramers. We found that intravenous injection of adenovirus-transduced DC
      stimulated the strongest OVA(aa257-264)-specific cytotoxic T-lymphocyte (CTL)
      responses although it delivered two orders of magnitude less antigen in vivo when
      compared to direct injection of recombinant adenovirus. We believe that our
      experimental approach has the potential to facilitate translational development
      of improved genetic immunization strategies targeting DC directly in vivo.

PMID- 16892457
TI  - Differential associations of beta-blockers with hemorrhagic events for chronic
      heart failure patients on warfarin.
AB  - PURPOSE: Beta-blockers have many different physiologic effects that could
      potentially influence the risk of hemorrhagic events in chronic heart failure
      patients (CHF) on warfarin. We examined how different beta-blockers vary in their
      associated risk of a hemorrhagic event. METHODS: We used databases from the
      Department of Veterans Affairs (VA) that contain information on medications
      prescribed, diagnoses, and hospitalizations. We identified patients with CHF on
      warfarin and either metoprolol, carvedilol, atenolol, or no beta-blocker during
      1999-2001. We modeled time to first hemorrhagic event using a Cox proportional
      hazards model, adjusting for age, ethnicity, comorbidities, and other factors.
      INR levels were examined in a subsample of 3546 patients. RESULTS: We identified
      66,988 CHF patients on warfarin. Hemorrhagic events occurred in 15.3% of the
      sample and, in 3.8% of the sample, the hemorrhage was considered severe. Compared
      to patients on carvedilol, the hazards ratio for a new hemorrhagic event was 1.25
      (1.17, 1.34) for no beta-blocker, 1.27 (1.18, 1.38) for atenolol, and 1.38 (1.28,
      1.48) for metoprolol. No differences in INR levels were evident among the four
      groups. CONCLUSIONS: The risk for a hemorrhagic event among CHF patients on
      warfarin may be affected by beta-blocker use and varies depending on which beta
      blocker is prescribed.

PMID- 16892458
TI  - Risk factors for statin-associated rhabdomyolysis.
AB  - PURPOSE: To identify and characterize risk factors for rhabdomyolysis in patients
      prescribed statin monotherapy or statin plus fibrate therapy. METHODS: A nested
      case-control study was conducted within a cohort of 252,460 new users of lipid
      lowering medications across 11 geographically dispersed U.S. health plans. Twenty
      one cases of rhabdomyolysis confirmed by medical record review were compared to
      200 individually matched controls without rhabdomyolysis. A conditional logistic
      regression model was applied to evaluate the effects of age, gender,
      comorbidities, concurrent medication use, dosage, and duration of statin use on
      the development of rhabdomyolysis. RESULTS: Statin users 65 years of age and
      older have four times the risk of hospitalization for rhabdomyolysis than those
      under age 65 (odds ratio (OR) = 4.36, 95% confidence interval (CI): 1.5,14.1). We
      also observed a joint effect of high statin dosage and renal disease (p = 0.022).
      When these two variables were added to the model with age, we obtained an OR of
      5.73 for dosage (95%CI: 0.63, 52.6) and 6.26 for renal disease (95%CI: 0.46,
      63.38). Although not statistically significant, we did observe a greater than
      twofold increase in risk for rhabdomyolysis among females (OR = 2.53, 95%CI:
      0.91, 7.32). CONCLUSIONS: Findings of this study indicate that older age is a
      risk factor for rhabdomyolysis among statin users. Although the evidence is not
      as strong, high statin dosage, renal disease, and female gender may be additional
      risk factors. Patients at higher risk of developing rhabdomyolysis should be
      closely monitored for signs and symptoms of the disease.

PMID- 16892459
TI  - Reduction of fat storage in mice fed a high-fat diet long term by treatment with
      saponins prepared from Kochia scoparia fruit.
AB  - The fresh fruit (Japanese name, Tonburi) of Kochia scoparia has been used as a
      food garnish in Japanese-style dishes from ancient times, and may prevent
      metabolic syndromes such as hyperlipidemia, hypertension, obesity and
      atherosclerosis. This study was performed to clarify whether an ethanol extract
      of K. scoparia fruit prevented obesity induced in mice by a high-fat diet for 9
      weeks. The ethanol extract of K. scoparia fruit prevented the increases in body
      weight and parametrial adipose tissue weight induced by the high-fat diet.
      Furthermore, consumption of a high-fat diet containing 1% or 3% K. scoparia
      extract significantly increased the fecal content and the fecal triacylglycerol
      level at day 3 compared with those in the high-fat diet group. The ethanol
      extract (250 mg/kg) and total saponins (100 mg/kg) of K. scoparia inhibited the
      elevation of the plasma triacylglyccerol level 2 or 3 h after the oral
      administration of the lipid emulsion. Total saponins, momordin Ic, 2'-O-beta-d
      glucopyranosyl momordin Ic and 2'-O-beta-d-glucopyranosyl momordin IIc isolated
      from K. scoparia fruit inhibited the pancreatic lipase activity (in vitro). These
      findings suggest that the anti-obesity actions of K. scoparia extract in mice fed
      a high-fat diet may be partly mediated through delaying the intestinal absorption
      of dietary fat by inhibiting pancreatic lipase activity.

PMID- 16892460
TI  - Treating threatened abortion with Chinese herbs: a case report.
AB  - In the report a patient who suffered from threatened abortion was successfully
      cured with Chinese herbs. After treatment, vaginal bleeding stopped and the
      aching sensation in the loins and prolapsing sensation in the abdomen
      disappeared. The gestational ring changed from a crescent moon shape to a normal
      shape.

PMID- 16892461
TI  - In vitro antiviral activities of Chinese medicinal herbs against duck hepatitis B
      virus.
AB  - Fifty-six different Chinese medicinal herbs from 29 families were evaluated for
      their antiviral activities against duck hepatitis B virus (DHBV) in vitro. The
      DHBV DNA level in primary duck hepatocyte cultures was monitored by dot blot
      hybridization and the cytotoxicity was evaluated by MTT assay. Anti-DHBV
      activities were found more strongly in the aqueous extracts of Ardisia chinensis
      and Pithecellobium clypearia with selective indices of 2.6 and >2.7,
      respectively, which were comparable to that of 2',3'-dideoxycytidine. Further
      research on the isolation of the active antiviral phytochemicals from these herbs
      may provide alternative options for the treatment of chronic hepatitis B.

PMID- 16892464
TI  - Preparation of holographic gratings of liquid crystals dispersed in polyurethane
      acrylates under controlled reaction conditions.
AB  - Transmission gratings of holographic polymer-dispersed liquid crystals (HPDLC)
      are prepared under controlled reaction conditions by adding various amounts of
      chain-transfer agent (CTA). The resulting films have a higher gel content with
      lower cross-link density, less dark reaction, less grating shrinkage with much
      smoother LC/polymer interfaces, smaller induction period, and fast saturation of
      diffraction efficiency, which shows a maximum of 95 % with 1 % CTA. An optimum LC
      content of 35 % is verified on the basis of morphology and reaction kinetics.

PMID- 16892465
TI  - Gadolinium-based mixed-metal nitride clusterfullerenes Gd(x)Sc(3-x)N@C80 (x=1,
      2).
AB  - The first gadolinium-based mixed-metal nitride clusterfullerenes Gd(x)Sc(3
      x)N@C(80) (I) (1, x=2; 2, x=1) have been successfully synthesized by the reactive
      gas atmosphere method and isolated facilely by recycling high-performance liquid
      chromatography (HPLC). The sum yield of 1 and 2 is 30-40 times higher than that
      of Gd(3)N@C(80) (I). Moreover, an enhanced relative yield of 2 over the
      Sc(3)N@C(80) (I) is achieved under the optimized synthesis conditions. According
      to the UV/Vis/NIR spectroscopic characterization, 1 and 2 are both stable
      fullerenes with large optical band-gaps while 1 has higher similarity to
      Gd(3)N@C(80) (I) and 2 resembles Sc(3)N@C(80) (I). The vibrational structures of
      1 and 2 are studied by Fourier-transform infrared (FTIR) spectroscopy as well as
      density functional theory (DFT) computations. In particular, the structures of
      the encaged Gd(x)Sc(3-x)N clusters within 1 and 2 are analyzed.

PMID- 16892462
TI  - ADAM 12 as a first-trimester maternal serum marker in screening for Down
      syndrome.
AB  - BACKGROUND: A Disintegrin And Metalloprotease 12 (ADAM 12) is a glycoprotein
      synthesised by placenta and it has been shown to be a potential first-trimester
      maternal serum marker for Down syndrome (DS) in two small series. Here we analyse
      further, the potential of ADAM 12 as a marker for DS in a large collection of
      first-trimester serum samples. MATERIALS AND METHODS: The concentration of ADAM
      12 was determined in 10-14-week pregnancy sera from 218 DS pregnancies and 389
      gestational age-matched control pregnancies, which had been collected as part of
      routine prospective first-trimester screening programs (DS = 105) or as part of
      previous research studies (DS = 113). ADAM 12 was measured using a semi-automated
      time resolved immunofluorometric assay and median values for normal pregnancies
      were established by polynomial regression. These medians were then used to
      determine population distribution parameters for DS and normal pregnancy groups.
      Correlation with previously established PAPP-A and free beta-hCG multiple of the
      medians (MoMs) and delta nuchal translucency (NT) were determined and used to
      model the performance of first-trimester screening with ADAM 12 in combination
      with other first-trimester markers at various time periods across the first
      trimester. The benefits of a contingent testing model incorporating early
      measurement of PAPP-A and ADAM 12 were also explored. RESULTS: The maternal serum
      concentration of ADAM 12 was significantly reduced (p = 0.0049) with an overall
      median MoM of 0.79 in the DS cases and a log(10) MoM SD of 0.3734 in the DS cases
      and 0.3353 in the controls. There was a significant correlation of ADAM 12 MoM in
      DS cases with gestational age (r = 0.375) and the median MoM increased from 0.50
      at 10-11 weeks to 1.38 at 13 weeks. ADAM 12 was correlated with maternal weight
      (r(controls) = 0.283), PAPP-A (r(controls) = 0.324, r(DS) = 0.251) but less so
      with free beta-hCG (r(controls) = 0.062, r(DS) = 0.049) and delta NT (r(controls)
      = 0.110, r(DS) = 0.151). ADAM 12 was significantly (p = 0.026) lower in smokers
      (0.87 vs 1.00) and elevated in Afro-Caribbean women compared to Caucasian women
      (1.34 vs 1.00). Population modelling using parameters from this and an earlier
      study showed that a combination of ADAM 12 and PAPP-A measured at 8-9 weeks and
      combined with NT and free beta-hCG measured at 12 weeks could achieve a detection
      rate of 97% at a 5% false-positive rate or 89% at a 1% false-positive rate. PAPP
      A and ADAM 12 alone at 8-9 weeks could identify 91% of cases at a 5% false
      positive rate. Using this as part of a contingent-screening model to select an
      intermediate risk group of women for NT and free beta-hCG at 11-12 weeks would
      enable the detection of 92% of cases with a 1% false-positive rate at a cost of
      providing NT and free beta-hCG for 6% of women with 94% of women having completed
      screening by the 10th week of pregnancy. CONCLUSION: ADAM 12 in early first
      trimester is a very efficient marker of DS. In combination with existing markers,
      it offers enhanced screening efficiency in a two-stage sequential first-trimester
      screening program or in a contingent-screening model, which may have benefits in
      health economies where universal access to high quality ultrasound is difficult.
      More data on early first-trimester cases with DS are required to establish more
      secure population parameters by which to assess further the validity of these
      models.

PMID- 16892466
TI  - Ligand-based virtual screening, parallel solution-phase and microwave-assisted
      synthesis as tools to identify and synthesize new inhibitors of mycobacterium
      tuberculosis.
AB  - In an attempt to identify new inhibitors of the growth of Mycobacterium
      tuberculosis (MTB), the causative agent of tuberculosis, a procedure for the
      generation, design, and screening of a ligand-based virtual library was applied.
      This used both an in silico protocol centered on a recursive partitioning (RP)
      model described herein, and a pharmacophoric model for antitubercular agents
      previously generated by our research group. Two candidates emerged from databases
      of commercially available compounds, both characterized by a minimum inhibitory
      concentration (MIC) of 25 microg mL(-1). Based on these compounds, two series of
      derivatives were synthesized by both parallel solution-phase and microwave
      assisted synthesis, leading to enhanced antimycobacterial activity. During both
      the design and synthesis, attention was focused on the efficient allocation of
      available resources with the aim of reducing the overall costs associated with
      calculation and synthesis.

PMID- 16892467
TI  - Variable-temperature measurements of the single-molecule conductance of double
      stranded DNA.

PMID- 16892468
TI  - Synthesis of triphosphorous bidentate phosphine-phosphoramidite ligands:
      application in the highly enantioselective hydrogenation of ortho-substituted
      aryl enamides.

PMID- 16892469
TI  - An [Fe(II) (3)O](4+) core wrapped by two [Fe(II)L(3)](-) units.

PMID- 16892470
TI  - Synthetic Peptide templates for molecular recognition: recent advances and
      applications.
AB  - The creation of molecular systems that can mimic some of the properties of
      natural macromolecules is one of the major endeavors in contemporary protein
      chemistry. However, the construction of artificial proteins with predetermined
      structure and function is difficult on account of complex folding pathways. The
      use of topological peptide templates has been suggested to induce and stabilize
      defined secondary and tertiary structures. This is because the recent advances in
      the chemistry of coupling reagents, protecting groups, and solid-phase synthesis
      have made the chemical synthesis of peptides with conformationally controlled and
      complex structures feasible. Besides their use as structure-inducing devices,
      these peptide templates can also be utilized to construct novel structures with
      tailor-made functions. Herein, we present recent advances in the field of peptide
      template-based approaches with particular emphasis on the demonstrated utility of
      this approach in molecular recognition, along with related applications.

PMID- 16892471
TI  - Single-chain magnet behavior in an alternated one-dimensional assembly of a
      Mn(III) Schiff-base complex and a TCNQ radical.
AB  - An alternated 1:1 chain compound of a Mn(III) salen derivative and the TCNQ
      monoradical was synthesized: [Mn(5-TMAMsaltmen)(TCNQ)](ClO(4))(2) (1)
      (TCNQ=tetracyano-p-quinodimethane; 5-TMAMsaltmen=N,N'-(1,1,2,2
      tetramethylethylene) bis(5-trimethylammoniomethylsalicylideneiminato)). Compound
      1 has a zigzag chain structure packed with adjacent chains with an interchain
      MnMn distance of over 8 Angatrom. As compound 1 contains no crystallization
      solvent, the void spaces between chains are occupied only by ClO(4) (-) counter
      ions. Compound 1 has a structure reminiscent of what has been observed in the
      family of Mn(III)(porphyrin)-TCNE or -TCNQ compounds reported previously by
      Miller and co-workers and we demonstrate herein its unique single-chain magnet
      behavior among this family of compounds. The direct current (dc) magnetic
      measurements established the one-dimensional nature of compound 1 with an
      antiferromagnetic exchange coupling, J/k(B) approximately -96 K, between the
      Mn(III) ion and TCNQ radical and with an activated correlation length
      (Delta(xi)=26.5 K) at low temperatures (50-15 K). The slow relaxation of the
      magnetization was shown in compound 1 by the field hysteresis of the
      magnetization observed below 3.5 K (with a coercive field up to 14 kOe at 1.8 K).
      Single-crystal magnetization measurements demonstrated the uniaxial symmetry of
      this compound and allowed an estimation of the anisotropy field, H(a)
      approximately 97 kOe. The absence of magnetic ordered phase or spin-glass
      behavior was established by heat-capacity calorimetry measurements that exhibit
      no abnormality of C(p) between 0.5 K and 10 K. The study of the magnetization
      relaxation by combined ac (alternating current) and dc techniques showed that
      compound 1 possesses a single relaxation time (tau). As the consequence of the
      finite size of the chain, the temperature dependence of tau presents two
      activated regimes above and below 4.5 K with tau(01)=2.1 x 10(-10) s,
      Delta(tau1)=94.1 K and tau(02)=6.8 x 10(-8) s and Delta(tau2)=67.7 K,
      respectively. The detailed analysis of these dynamics properties together with
      the correlation length, allows an unambiguous demonstration of the single-chain
      magnet behavior in 1.

PMID- 16892472
TI  - Supramolecular self-organization of "Janus-like" diblock codendrimers: synthesis,
      thermal behavior, and phase structure modeling.
AB  - We report on the design and synthesis of three series of segmented amphiphilic
      block codendrimers, and on their self-organizing behavior in liquid-crystalline
      mesophases. Connecting two prefunctionalized monodendrons, each differing in
      their chemical constitution and generation number, yielded these diblock
      supermolecules. One wedge of the codendrimer was made hydrophobic, and is based
      on a branched poly(benzyl ether) monodendron functionalized at the periphery by
      lipophilic aliphatic fragments (also known as Percec dendrons). The other segment
      was made hydrophilic by the grafting of hydroxyl-containing moieties onto the
      focal functions of the former dendrons. Both types of dendrons were prepared
      independently by convergent methods and then joined in the ultimate stage of the
      synthetic procedure by cross-coupling reactions. In this way, the proportion of
      the dendritic blocks was varied independently to allow control of the
      hydrophilic/hydrophobic balance (HHB), the hydrogen-bonding ability, and
      consequently the capacity to tune the mesomorphic properties of the resulting
      "superamphiphiles" was anticipated. Essentially all the dendritic compounds
      display a thermotropic mesomorphism directly at or near room temperature as
      determined by using X-ray diffraction, polarized optical microscopy, and
      differential scanning calorimetry. The nature and the supramolecular organization
      of the mesophases, namely columnar and cubic phases, are correlated to the size
      of the respective block monodendrons and the chemical structures of the
      dendromesogens. The molecular organization within the cubic phases can be
      geometrically described and well understood by the space-filling polyhedron
      model.

PMID- 16892473
TI  - The domino chemistry approach to molecular complexity: competing domino processes
      modulated by the substitution pattern.
AB  - Oxidative cleavage with lead tetraacetate results in the synthesis of different
      oxygen heterocycles starting from the same unsaturated 1,2-diol of type I by
      tuning of the substitution pattern at the angular position. When this compound
      bears a functional substituent, such as an alkoxy, ester, alkenyl, or simply a
      hydrogen, more than one reaction pathway are in competition. The process allows
      for the selective formation of three different complex ring systems, by the
      appropriate choice of the angular substituent, leading to either a ring-expanded
      type 1, ring-retained type 2, or domino products 3.

PMID- 16892474
TI  - Phane properties of [2.2]paracyclophane/dehydrobenzoannulene hybrids.
AB  - A series of [2.2]paracyclophane/dehydrobenzo[14]annulene (PC/DBA) hybrids
      (hydrocarbons 5, 6, 9, 10 b, and 10 c), [2.2]paracyclophane/dehydro[14]annulene
      (PC/DA) hybrids (7 and 8) and suitable model systems (11, 12, and 33) has been
      synthesized. Comparison of the electronic absorption spectra in each series of
      compounds provides further insight into the global communication between the
      decks in the [2.2]paracyclophane unit.

PMID- 16892476
TI  - Hierarchically structured nanocomposite films as highly sensitive chemosensory
      materials for TNT detection.

PMID- 16892475
TI  - The molecular basis of self-assembly of dendron-rod-coils into one-dimensional
      nanostructures.
AB  - We describe here a comprehensive study of solution and solid-state properties of
      self-assembling triblock molecules composed of a hydrophilic dendron covalently
      linked to an aromatic rigid rod segment, which is in turn connected to a
      hydrophobic flexible coil. These dendron-rod-coil (DRC) molecules form well
      defined supramolecular structures that possess a ribbonlike morphology as
      revealed by transmission-electron and atomic-force microscopy. In a large variety
      of aprotic solvents, the DRC ribbons create stable networks that form gels at
      concentrations as low as 0.2% by weight DRC. The gels are thermally irreversible
      and do not melt at elevated temperatures, indicating high stability as a result
      of strong noncovalent interactions among DRC molecules. NMR experiments show that
      the strong interactions leading to aggregation involve mainly the dendron and
      rodlike blocks, whereas oligoisoprene coil segments remain solvated after
      gelation. Small-angle X-ray scattering (SAXS) profiles of different DRC molecules
      demonstrate an excellent correlation between the degree-of-order in the solid
      state and the stability of gels. Studies on two series of analogous molecules
      suggest that self-assembly is very sensitive to subtle structural changes and
      requires the presence of at least four hydroxyl groups in the dendron, two
      biphenyl units in the rod, and a coil segment with a size comparable to that of
      the rodlike block. A detailed analysis of crystal structures of model compounds
      revealed the formation of stable one-dimensional structures that involve two
      types of noncovalent interactions, aromatic pi-pi stacking and hydrogen bonding.
      Most importantly, the crystal structure of the rod-dendron compound shows that
      hydrogen bonding not only drives the formation of head-to-head cyclic structures,
      but also generates multiple linkages between them along the stacking direction.
      The cyclic structures are tetrameric in nature and stack into ribbonlike objects.
      We believe that DRC molecules utilize the same arrangement of hydrogen bonds and
      stacking of aromatic blocks observed in the crystals, explaining the exceptional
      stability of the nanostructures in extremely dilute solutions as well the thermal
      stability of the gels they form. This study provides mechanistic insights on self
      assembly of triblock molecules, and unveils general strategies to create well
      defined one-dimensional supramolecular objects.

PMID- 16892477
TI  - The possibility of a liquid superconductor.
AB  - All superconductors are solids in their superconducting state, this canonical
      electronic state of matter presently having only been observed well below the
      melting temperature of the solid. The discovery of high-temperature
      superconductivity in cuprates has widened significantly our horizons of the
      theoretical understanding of the physical phenomenon. A number of observations
      point to the possibility that superconductors with a high superconducting
      transition temperature may not be conventional Bardeen-Cooper-Schrieffer (BCS)
      superconductors, but rather derive from the Bose-Einstein condensation of real
      space pairs. While BCS superconductors exist in the solid state (probably with
      the exception of metallic liquid hydrogen at ultrahigh pressures), we argue here
      that a superconducting charged Bose liquid may be found in a true liquid state of
      condensed matter at ambient pressure. An experimental scenario is outlined in
      fluid metal-ammonia solutions for stabilizing and observing a high-temperature
      superconducting liquid (ca. 230 K) or at least a vitreous superconductor in the
      corresponding quenched solutions (ca. 160 K).

PMID- 16892479
TI  - Enantiomeric separation of acidic compounds using single-isomer amino
      cyclodextrin derivatives in nonaqueous capillary electrophoresis.
AB  - The enantiomeric separation of a series of acidic pharmaceuticals (mostly
      nonsteroidal anti-inflammatory drugs) has been investigated in NACE systems using
      single-isomer amino beta-CD derivatives. The first part of this study consisted
      of the selection of the basic experimental conditions to separate efficiently the
      enantiomers of acidic drugs. Several parameters, such as the nature of the ionic
      BGE components, were studied and a methanolic solution of ammonium acetate
      containing the cationic CD was selected as BGE. A D-optimal design with 20
      experimental points was then applied and the nature and concentration of the CD
      were found to have a significant effect on the enantiomeric resolution for all
      studied compounds. Resolution (R(s)) values were always higher with 6-monodeoxy-6
      mono(3-hydroxy)propylamino-beta-CD (PA-beta-CD) compared to those obtained with 6
      monodeoxy-6-mono(2-hydroxy)propylamino-beta-CD (IPA-beta-CD). However, the latter
      led to shorter migration times. Generic NACE conditions were then selected by
      means of the multivariate approach in order to obtain the highest R(s) values in
      a minimum amount of time. Finally, dependence of separation selectivity,
      resolution, as well as mobility difference on chiral selector concentration was
      discussed and binding constants with PA-beta-CD were estimated for the two
      enantiomers of one of the model compounds, suprofen in these NACE systems.

PMID- 16892480
TI  - Nanostructured polymer matrix for oligonucleotide separation.
AB  - A nanostructured copolymer matrix has successfully separated oligonucleotides
      with high resolution by CE using a very short separation channel which simulates
      the real microchip condition for the first time. The triblock copolymer,
      E(45)B(14)E(45) (B20-5000) with E, B, and subscript denoting oxyethylene,
      oxybutylene, and segment length, respectively, has a unique temperature-dependent
      viscosity-adjustable property and a dynamic coating ability in 1xTBE buffer (89
      mM Tris, 89 mM boric acid, 2 mM EDTA in Milli-Q water). The B-block is
      hydrophilic at low temperatures, e.g., 4 degrees C, and the polymer solution has
      a very low viscosity of about 100 cP in a 32.5% w/v solution. At room
      temperatures, the B-block becomes hydrophobic due to a breakdown of hydrogen
      bonds between B-blocks and water, and the polymer matrix forms a body-centered
      cubic structure at high concentrations. Oligonucleotide sizing markers ranging
      from 8 to 32 base could be successfully separated with one-base resolution in a
      1.5 cm long separation channel by E(45)B(14)E(45) in its gel-like state.

PMID- 16892481
TI  - Using in situ rheology to characterize the microstructure in photopolymerized
      polyacrylamide gels for DNA electrophoresis.
AB  - Photopolymerized cross-linked polyacrylamide hydrogels are attractive sieving
      matrix formulations for DNA electrophoresis owing to their rapid polymerization
      times and the potential to locally tailor the gel pore structure through spatial
      variation of illumination intensity. This capability is especially important in
      microfluidic systems, where photopolymerization allows gel matrices to be
      precisely positioned within complex microchannel networks. Separation performance
      is also directly related to the nanoscale gel pore structure, which is in turn
      strongly influenced by polymerization kinetics. Unfortunately, detailed studies
      of the interplay among polymerization kinetics, mechanical properties, and
      structural morphology are lacking in photopolymerized hydrogel systems. In this
      paper, we address this issue by performing a series of in situ dynamic small
      amplitude oscillatory shear measurements during photopolymerization of cross
      linked polyacrylamide electrophoresis gels to investigate the relationship
      between rheology and parameters associated with the gelation environment
      including UV intensity, monomer and cross-linker composition, and reaction
      temperature. In general, we find that the storage modulus G' increases with
      increasing initial monomer concentration, cross-linker concentration, and
      polymerization temperature. The steady-state value of G', however, exhibits a
      more complex dependence on UV intensity that varies with gel concentration. A
      simple model based on rubber elasticity theory is used to obtain estimates of the
      average gel pore size that are in surprisingly good agreement with corresponding
      data obtained from analysis of DNA electrophoretic mobility in gels cast under
      identical polymerization conditions.

PMID- 16892482
TI  - Degradingdehydroabietylisothiocyanate as a chiral derivatizing reagent for
      enantiomeric separations by capillary electrophoresis.
AB  - Abietic acid is a naturally occurring enantiomeric diterpenic acid. Its absolute
      optical purity and very stable stereochemistry structure makes it an excellent
      starting material for preparing chiral derivatizing reagents for chromatographic
      or electrophoretic applications. This paper describes the synthesis and
      evaluation of a novel chiral derivatization reagent, i.e.,
      degradingdehydroabietylisothiocyanate (DDHAIC) derived from dehydroabietic acid.
      Its applicability for the enantioseparation of racemic amino acids by CE was
      demonstrated. DDHAIC reacted readily with amino acids at an elevated temperature
      (70 degrees C). The resulting derivatives were highly stable and separable by
      MEKC. Separation of amino acid-DDHAIC diastereomers was achieved with a running
      buffer consisting of 50 mM Na(2)HPO(4) (pH 9.0), 18 mM SDS, and 25% v/v ACN.
      Under the conditions selected, diastereomers formed from ten pairs of tested
      amino acid enantiomers including D/L-Asn, D/L-Met, D/L-Leu, D/L-Phe, D/L-Trp, D/L
      Ser, D/L-Val, D/L-Ala, D/L-Thr, and R/S-vigabatrin were well resolved. The
      resolution values were in the range of 0.95-8.9.

PMID- 16892483
TI  - Simultaneous determination of ethamsylate, tramadol and lidocaine in human urine
      by capillary electrophoresis with electrochemiluminescence detection.
AB  - Ethamsylate, tramadol and lidocaine, partly excreted by the kidney, are generally
      used as hemostatic, analgesic and local anesthetic in surgery. We developed a
      simple and sensitive method for their simultaneous monitoring in human urine
      based on CE coupled with electrochemiluminescence detection by end-column mode.
      Under optimized conditions the proposed method yielded linear ranges from 5.0 x
      10(-8) to 5.0 x 10(-5), 1.0 x 10(-7) to 1.0 x 10(-4) and 1.0 x 10(-7) to 1.0 x
      10(-4) M with LODs of 8.0 x 10(-9) M (36 amol), 1.6 x 10(-8) M (72 amol) and 1.0
      x 10(-8) M (45 amol) (S/N = 3) for ethamsylate, tramadol and lidocaine,
      respectively. The RSD for their simultaneous detection at 1.0 x 10(-6) M was 2.1,
      2.8 and 3.2% (n = 7), respectively. For practical application an extraction step
      with ethyl acetate at pH 11 was performed to eliminate the influence of the
      sample ionic strength. The recoveries of ethamsylate, tramadol and lidocaine at
      different levels in human urine were between 87 and 95%. This method was used for
      simultaneous detection of ethamsylate, tramadol and lidocaine in clinic urine
      samples from two medicated patients. It was valuable in clinical and biochemical
      laboratories for monitoring these drugs for various purposes.

PMID- 16892484
TI  - Proteomic analysis of pulmonary sclerosing hemangioma.
AB  - Sclerosing hemangioma (SH) is a rare benign pulmonary tumor derived from the
      primitive respiratory epithelium. However, the pathogenesis of SH has not yet
      been clear. Surfactant protein, thyroid transcription factor-1, epithelial
      membrane antigen, cytokeratin, and vimentin have been identified in SH by
      immunohistochemistry and electron microscopy. To identify proteins specifically
      regulated in SH, 2-D PAGE was performed using SH and paired normal tissues. Ten
      selected differentially expressed protein spots were identified by PMF, MALDI-TOF
      MS, and database searching. Apolipoprotein A-1, antizyme inhibitor, heat shock 27
      kDa protein 1, and antioxidant proteins, such as peroxiredoxin II (Prx II) and
      GST, were identified among the down-regulated proteins in SH. Western blot and
      immunohistochemistry confirmed reduced expressions of Prx II and GST in SH versus
      normal lung tissue. This study is the first report on the reduced expressions of
      Prx II and GST in SH.

PMID- 16892485
TI  - Reconstructing protein complexes: from proteomics to systems biology.
AB  - Modern high throughput technologies in biological science often create lists of
      interesting molecules. The challenge is to reconstruct a descriptive model from
      these lists that reflects the underlying biological processes as accurately as
      possible. Once we have such a model or network, what can we learn from it?
      Specifically, given that we are interested in some biological process associated
      with the model, what new properties can we predict and subsequently test? Here,
      we describe, at an introductory level, a range of bioinformatics techniques that
      can be systematically applied to proteomic datasets. When combined, these methods
      give us a global overview of the network and the properties of the proteins and
      their interactions. These properties can then be used to predict functional
      pathways within the network and to examine substructure. To illustrate the
      application of these methods, we draw upon our own work concerning a complex of
      186 proteins found in neuronal synapses in mammals. The techniques discussed are
      generally applicable and could be used to examine lists of proteins involved with
      the biological response to electric or magnetic fields.

PMID- 16892486
TI  - FPRL-1 induces modifications of migration-associated proteins in human
      neutrophils.
AB  - Human polymorphonuclear neutrophils (PMNs) are an important cell population of
      the innate immune system, which migrates following concentration gradients of
      chemokines or chemoattractants to locations of infection and inflammation in
      order to eliminate invading microorganisms and cell debris. For both migration
      and adhesion of PMNs to various tissues, the dynamic remodeling of the
      cytoskeleton is key prerequisite. In this context, the formyl peptide receptor
      like 1 (FPRL-1) is an important chemoattractant receptor expressed on PMNs. In
      this study, we show that a short stimulation of FPRL-1 with either a synthetic
      peptide ligand (W-peptide) or a natural ligand (sCKbeta8-1) changes the protein
      pattern of PMNs as assessed by 2-D-DIGE. MS analysis of selected deregulated
      protein species resulted in the identification of proteins that are involved in
      the remodeling process of the actin- and tubulin-based cytoskeleton, such as L
      plastin, moesin, cofilin, and stathmin. Subsequent validation experiments
      performed either by Western blotting or phosphoprotein-specific gel staining (Pro
      Q Diamond) revealed that L-plastin is phosphorylated, whereas moesin, cofilin,
      and stathmin are dephosphorylated in PMNs upon FPRL-1 stimulation. These findings
      suggest that FPRL-1 signaling targets proteins that regulate the motility of PMNs
      and moreover show that 2-D-DIGE is a technique capable of detecting and
      quantifying differently modified (e.g., phosphorylated) protein variants.

PMID- 16892487
TI  - Proteomic analysis of the autoantibody response following immunization with a
      single autoantigen.
AB  - In most autoimmune diseases, the autoantibody response is directed against
      several antigens of the target organ whose identification is crucial for
      understanding the physiopathological process. Thus, technologies allowing a
      characterization of the whole autoantibody pattern of both human and experimental
      autoimmune diseases are required. Here we have used immunoproteomic analysis of
      human epidermal extracts to characterize the diversity of the anti-desmosome
      antibody response induced in normal mice immunized with desmoglein 1, the major
      autoantigen of pemphigus foliaceus, an autoimmune blistering skin disease. In
      particular, this analysis enables us to characterize the binding properties of
      anti-desmosome mAbs derived from these mice and to show that the autoantibody
      response induced upon immunization with a single autoantigen targets different
      epidermal autoantigens with a pattern similar to that observed in certain variety
      of human pemphigus.

PMID- 16892488
TI  - Protein expression profiles of early embryos--an important step in the right
      direction: just not quite ready for prime time.

PMID- 16892489
TI  - Interpretations of multinucleation--is it ever normal?

PMID- 16892490
TI  - Oral contraceptives and insulin sensitivity.

PMID- 16892491
TI  - The ever-rising spiral of technology and cost.

PMID- 16892493
TI  - Bibliography. Current world literature. Infectious arthritis and immune
      dysfunction.

PMID- 16892494
TI  - Bibliography. Current world literature. Metabolic bone disease.

PMID- 16892492
TI  - Retraction to "Overexpression of cyclooxygenase-2 in nasopharyngeal carcinoma and
      association with lymph node metastasis" [Oral Oncol. 41 (2005) 903-908].

PMID- 16892495
TI  - Its the worms' turn.

PMID- 16892496
TI  - Brain study reveals neurobiology of dread.

PMID- 16892497
TI  - Adolescents' drinking habits predict later occurrence of traumatic brain injury:
      35-year follow-up of the northern Finland 1966 birth cohort.
AB  - PURPOSE: To examine the relationship between adolescents' drinking habits and the
      risk of traumatic brain injury. METHOD: We prospectively studied the 10,424
      adolescents from northern Finland who were born during the year 1966 after
      exclusion of those who died or emigrated. Data on the frequencies of alcohol use
      and drunkenness after alcohol intake were collected at the age of 14 years, and
      the subjects were thereafter followed up until the age of 35 years. The traumatic
      brain injuries (TBI) that had occurred after the age of 14 years were recorded
      from the Finnish Hospital Discharge Register and the Registry for Causes of Death
      by Statistics Finland. RESULTS: Compared with never-drinkers, those who drank
      alcohol once a month or more often(frequent drinkers) or had sometimes been drunk
      before the age of 14 years had an increased crude relative risk of TBI during the
      follow-up time of 21 years (relative risk [RR] 2.04; 95% confidence interval [CI]
      1.06 -3.93 and RR 1.42; 95% CI 1.08 -1.88 for frequent alcohol use and
      drunkenness,respectively). Adjusted (for fathers' occupation, family background,
      place of residence and school performance) RRs for TBI during the 21-year follow
      up were 2.21 (1.14-4.29) and 1.35 (1.01-1.79), respectively. CONCLUSIONS: The
      habit of frequent drinking and the feeling of having been drunk at the age of 14
      years or before seem to increase the risk for TBI in adolescence and young
      adulthood. Increased efforts should be made by policy makers to restrict
      adolescents= alcohol drinking.

PMID- 16892498
TI  - Coping with social physique anxiety in adolescence.
AB  - PURPOSE: To explore how adolescents cope with social physique anxiety. METHODS:
      Participants were 398 female (mean age of 15.4 years, SD = 1.3) and 223 male
      (mean age of 15.4 years, SD = 1.1) adolescents who provided open-ended responses
      to a self-identified situation in which they experienced social physique anxiety.
      A codebook of 24 dimensions was developed to code participants' coping
      strategies. Measures of state and trait social physique anxietyand coping
      function were also completed. RESULTS: Females had significantly higher mean
      values than males on social physique anxiety scales and emotion-focused coping
      function. Females reported a total of 1051 strategies and males reported 473
      coping strategies. The most commonly reported coping strategies were behavioral
      avoidance(reported by 41.5% of females and 33.2% of males), appearance management
      (39.9% females,24.4% males), social support (22.1% females, 17.1% males),
      cognitive avoidance (20.4% females,18.7% males), and acceptance (19.6% females,
      29.0% males). Social physique anxiety in the self-identified situation was
      related to both trait social physique anxiety (r = .44, females; r = .36,males)
      and the number of strategies reported (r = .21, females; r = .23, males).
      CONCLUSIONS: First, this study provides important insight into the wide range of
      cognitive and behavioral coping strategies adolescents use to manage social
      physique anxiety. Second, the development of the codebook that was necessary to
      code the adolescents' open-ended coping responses has the potential to act as a
      starting point as a taxonomy for coping in the body domain.

PMID- 16892499
TI  - Asian/Pacific Islander youth violence prevention center: interpersonal violence
      and deviant behaviors among youth in Hawai'i.
AB  - PURPOSE: This study investigates the prevalence rates of violent and deviant
      behaviors among a sample of Filipino, Hawaiian, Japanese, and Samoan public high
      school students residing in Hawai'i, and is the first relatively large-scale
      study of its kind regarding a disaggregated sample of Asian American and Pacific
      Islander (AAPI) youth. Filipino, Hawaiian, and Samoan adolescents were the chosen
      ethnic groups for this study's focus due to their over-representation in
      Hawai'i's juvenile justice system. METHODS: Data for this study were gathered
      collaboratively by researchers, community groups, and school officials who agreed
      that youth violence was a community concern worthy of deeper understanding and
      community response. The study's process included three phases: a focus group
      consultation phase, field-testing, and the final risk and protective factor
      study. For the final study, 326 randomly selected students representing three
      Hawai'i public high schools were surveyed on a one-on-one basis.A smaller sample
      of Japanese students was also included in the study, serving as a control group.
      RESULTS: Findings illustrate the importance of disaggregating specific ethnic and
      gender groups within the AAPI ethnic category when examining adolescent issues.
      As examples, Samoan youth reported significantly higher rates of violence than
      other ethnic groups surveyed, and Hawaiian girls reported higher rates of
      substance use than Hawaiian boys, which was not commensurate with other ethnic
      groups. Filipino, Hawaiian, and Samoan youth all reported significantly higher
      rates than Japanese on overall deviant behavior. CONCLUSIONS: Implications for
      further research and community development include enhancing minority youths'
      bicultural self-efficacy.

PMID- 16892500
TI  - Counterpoint: cardiovascular variability is not an index of autonomic control of
      the circulation.

PMID- 16892501
TI  - Insect immunity: the post-genomic era.
AB  - Insects have a complex and effective immune system, many components of which are
      conserved in mammals. But only in the last decade have the molecular mechanisms
      that regulate the insect immune response--and their relevance to general biology
      and human immunology--become fully appreciated. A meeting supported by the Centre
      National de la Recherche Scientifique (France) was held to bring together the
      whole spectrum of researchers working on insect immunity. The meeting addressed
      diverse aspects of insect immunity and brought together geneticists working on
      Drosophila melanogaster with those working on other insects.

PMID- 16892502
TI  - Cardiovascular variability is/is not an index of autonomic control of
      circulation.

PMID- 16892503
TI  - Cardiovascular variability is/is not an index of autonomic control of
      circulation.

PMID- 16892504
TI  - Cardiovascular variability is/is not an index of autonomic control of
      circulation.

PMID- 16892505
TI  - Cardiovascular variability is/is not an index of autonomic control of
      circulation.

PMID- 16892506
TI  - Cardiovascular variability is/is not an index of autonomic control of
      circulation.

PMID- 16892507
TI  - Anisotropic scaffolds facilitate enhanced neurite extension in vitro.
AB  - Tissue engineering (TE) techniques to enhance nerve regeneration following nerve
      damage have had limited success in matching the performance of autografts across
      short nerve gaps (< 10 mm). For regeneration over longer nerve gaps, TE
      techniques have been less successful than autografts. Most engineered scaffolds
      do not present directional cues to the regenerating nerves. In our efforts to
      design a TE scaffold to replace the autograft, we hypothesize that anisotropic
      hydrogel scaffolds with gradients of a growth-promoting glycoprotein, laminin-1
      (LN-1), may promote directional neurite extension and enhance regeneration. In
      this study we report the engineering of three-dimensional (3D) agarose scaffolds
      with photoimmobilized gradients of LN-1 of differing slopes. Dorsal root ganglia
      (DRG) from chicken embryos were cultured in the agarose scaffolds and their
      neurite extension rate was determined. DRG neurite extension rates were
      significantly higher in the anisotropic scaffolds, with a maximal growth rate in
      an anisotropic scaffold twice that of the maximal growth rate in isotropic
      scaffolds of LN-1. We suggest that these anisotropic scaffolds, presenting an
      optimal gradient of LN-1, may significantly impact nerve regeneration. Such
      anisotropic scaffolds may represent a new generation of tissue engineered
      materials with built-in directional cues for guided tissue or nerve regeneration.

PMID- 16892508
TI  - [Glaucoma: early diagnosis is central].

PMID- 16892509
TI  - Circumcision complications.

PMID- 16892510
TI  - Bad medicine, bad reportage, or both?

PMID- 16892511
TI  - Letter to the editor re: JAMA article on L-arginine therapy in acute myocardial
      infarction.

PMID- 16892512
TI  - Generalism in the specialisms.

PMID- 16892513
TI  - Use of diagnostic imaging in Australian general practice.

PMID- 16892514
TI  - Breast cancer screening.

PMID- 16892516
TI  - The dose of aspirin for the prevention of cardiovascular and cerebrovascular
      events.
AB  - BACKGROUND: Low dose aspirin (ASA) (75-325 mg daily) is commonly used for the
      secondary prevention of cardiovascular and cerebrovascular events, as recommended
      by US national guidelines. Questions remain, however, as to whether there is a
      difference in the efficacy and safety across this low dose range. SCOPE: Double
      blind controlled studies, meta-analyses, and observational analyses were reviewed
      to assess the body of evidence regarding the safety and efficacy of aspirin
      dosing. FINDINGS: Only one double-blind study directly compared two doses of
      aspirin within the recommended low dose range. No difference in efficacy or
      safety was observed, although there was a trend toward greater efficacy with ASA
      325 mg vs. ASA 81 mg. Three meta-analyses did not find a difference in bleeding
      events within the low dose range, while one found that higher doses were
      associated with more events. One meta-analysis found ASA 75-150 mg was as
      effective as ASA 160-325 mg. Observational analyses of low dose (75-325 mg) ASA
      from two large controlled trials differed in their results. One study found no
      difference in the number of cardiovascular/cerebrovascular events, and a
      significant improvement in mortality with higher doses, while the other found
      that higher doses were associated with more events. CONCLUSION: There does not
      appear to be a difference in safety across the low dose range of 75-325 mg based
      on randomized controlled trial data. Furthermore, ASA 325 mg daily appears to be
      at least as effective as 75 mg daily. Since the optimal dose of ASA for primary
      and secondary prevention of events in the broad population is uncertain, dosing
      considerations should include an evaluation of a patient's individual clinical
      status as well as an overall cardiovascular and cerebrovascular benefit vs. risk
      assessment.

PMID- 16892517
TI  - Medical devices; immunology and microbiology devices; classification of fecal
      calprotectin immunological test systems. Final rule.
AB  - The Food and Drug Administration (FDA) is classifying fecal calprotectin
      immunological test systems into class II (special controls). The special control
      that will apply to these devices is the guidance document entitled, "Class II
      Special Controls Guidance Document: Fecal Calprotectin Immunological Test
      Systems." The agency is classifying these devices into class II (special
      controls) in order to provide a reasonable assurance of safety and effectiveness
      of these devices. Elsewhere in this issue of the Federal Register, FDA is
      announcing the availability of a guidance document that will serve as the special
      control for these devices.

PMID- 16892518
TI  - Definition of psychoses for certain VA purposes. Final rule.
AB  - This document amends the Department of Veterans Affairs (VA) adjudication
      regulations to define the term "psychosis." The term is used but not defined in
      certain statutes that provide presumptive service connection for compensation.
      The intended effect of this amendment is consistent application of these
      statutory provisions.

PMID- 16892519
TI  - Cold, cough, allergy, bronchodilator, and antiasthmatic drug products for over
      the-counter human use; amendment of monograph for OTC nasal decongestant drug
      products. Final rule.
AB  - The Food and Drug Administration (FDA) is issuing a final rule to amend the final
      monograph (FM) for over-the-counter (OTC) nasal decongestant drug products (drug
      products used to relieve nasal congestion due to a cold, hay fever, or other
      upper respiratory allergies) to add phenylephrine bitartrate (PEB), both
      individually and in combination drug products in an effervescent dosage form, as
      generally recognized as safe and effective (GRASE). An effervescent dosage form
      is intended to be dissolved in water before taking by mouth. This final rule is
      part of FDA's ongoing review of OTC drug products.

PMID- 16892520
TI  - Third conference on epileptogenesis. S Servolo Island, Venice, Italy, July 27-30,
      2005.

PMID- 16892521
TI  - Health care disconnect: gaps in coverage and care for minority adults. Findings
      from the Commonwealth Fund Biennial Health Insurance Survey (2005).
AB  - Analysis of the Commonwealth Fund Biennial Health Insurance Survey (2005) finds
      that uninsured rates for Hispanic and African American adults are one and-a-half
      to three times greater than the rate for white adults. Nearly two-thirds (62%) of
      working-age Hispanics and one-third (33%) of African Americans were uninsured at
      some point during 2005, compared with 20 percent of working-age whites. Hispanics
      are particularly disconnected from the health care system, being substantially
      less likely than whites to have a regular doctor, to have visited a doctor in the
      past year, or to feel confident about their ability to manage their health
      problems. African Americans are significantly more likely than whites to visit
      the emergency room for non-urgent care and to experience serious problems with
      medical bills and medical debt. Along with expanded insurance coverage, policies
      promoting continuity in patients' relationships with health care providers also
      are needed to reduce disparities in access.

PMID- 16892522
TI  - [In memory of Professor Aleksandar Kostic].

PMID- 16892523
TI  - Going single, but not alone.

PMID- 16892524
TI  - Embryos and biopsies on the ChIP-ing forecast.
AB  - UK researchers have devised a method of chromatin immunoprecipitation that
      requires as little as 100 cells, opening the door to epigenetics studies in
      primary cells and embryos.

PMID- 16892525
TI  - An affinity for new proteins.
AB  - Metabolic incorporation of an unnatural amino acid allows researchers to rapidly
      affinity purify newly synthesized proteins from mammalian cell lysates for direct
      identification by mass spectrometry.

PMID- 16892526
TI  - Circuit maps for the cell.
AB  - An assessment of the interactions between different receptor-mediated cellular
      signaling pathways may have revealed an unexpected degree of underlying
      compartmentalization and even simplicity in the cross-talk between these
      networks.

PMID- 16892527
TI  - Awareness. Holy Name Hospital, Teaneck, NJ.
AB  - In New Jersey, Holy Name Hospital, a 361-bed facility, has launched a campaign to
      announce the arrival of the new director of the Interventional Institute. The
      hospital's marketing team created radio spots, print ads, and freestanding
      inserts to alert the general pubic about the new doctor on staff, who comes with
      a world class reputation. The campaign features print ads with testimonials from
      real-life patients who have successfully undergone the interventional surgery.

PMID- 16892529
TI  - [Barriers to objective diagnosis and individual prognosis--it gets light].

PMID- 16892528
TI  - Branding. Presbyterian Hospital of Dallas, TX.
AB  - To help position Presbyterian Hospital of Dallas as a referral center rather than
      a large community hospital, the facility launched an aggressive multiphase
      campaign, with Phase I already underway as of April. By using real-life patient
      testimonials to highlight procedures, technologies, and services not offered by
      competitors, the effort hopes to increase brand recognition in the Dallas area.

PMID- 16892530
TI  - [Pathology in Rostock].
AB  - The name of Rostock was first mentioned in 1161 by the Danish historian Saxo
      Grammaticus. As the oldest university in Northern Europe, the Alma mater
      rostochiensis was inaugurated in 1419 and is proudely called Light of the North
      ("Leuchte des Nordens"). Its Medical Faculty belonged to the three founding
      faculties. As elsewhere, the roots of Rostock pathology hark back to anatomy. A
      Theatrum anatomicum existed since 1790. First lectures on pathology were read by
      Johann Wilhelm Josephi (1763-1845) who was Head of Anatomy in the so-called
      Dissection House ("Zergliederungshaus") situated at the Old Market of Rostock. In
      1844, anatomy together with its pathology rooms moved into the Garden House
      ("Gartenhaus") on the university yard. From 1878 to 1930, the Pathology
      represented one section of the downtown Medical Studies Building. From 1930 up to
      now, the Pathology Institute is situated in the Strempel Street at the corner of
      the clinical center. The Rostock Pathology Chair was established in 1865. Since
      that time, the institute had ten directors. Inter alios, Ernst Schwalbe (1871
      1920) was a famous teratologist at the beginning of the 20th century. Walther
      Fischer (1882-1969) was Head of Institute for 24 years and became well-known as
      oncopathologist. After World War II, Alexander Bienengraber (1911-1990)
      reconstructed the institute in all ist compartments to a modern standard. At
      present, about 40 persons, with eight pathologists among them, represent the
      staff of the institute. 150 medical students are taught in each semester.
      Scientific topics concern oral, colorectal and thyroid carcinoma, pancreatitis as
      well as renal and transplant pathology. Nearly 15,000 histology, 20,000 cytology,
      and 150 autopsy cases are presently examined per year.

PMID- 16892531
TI  - Liver allograft pathology and biopsy interpretation.
AB  - In many instances liver histology remains the "gold standard" for the diagnosis
      of allograft dysfunction, although progresses in imaging techniques, Doppler
      blood flow investigation and the availability of serum viral or other markers
      have somewhat reduced the need for needle biopsy in some situations. Equally,
      these newly developed techniques have improved our understanding of confounding
      histological changes. In the early stages after surgery harvesting injury,
      ischaemia due to interference with arterial blood supply, especially in the young
      patient, early biliary and/or septic complications have to be distinguished from
      the classical triad whose relative importance of its 3 components remains
      incompletely understood. Later in the post transplant course, the differential
      diagnosis broadens to include late cellular rejection with possible evolution
      into chronic rejection, late biliary complications, in particular ischaemic
      cholangitis, de novo or reactivated viral infection, drug toxicity, and potential
      recurrence of the primary disease, in particular autoimmune disorders and viral
      hepatitides. Multiple pathologies are not exceptional and should this happens,
      the putative aetiologies have to be put in order of clinical relevance,
      especially hepatitis C or B recurrence, and the frequently associated, yet
      generally mild cellular rejection. Some features such as perivenular cell
      dropout, chronic hepatitis or architectural anomalies may be difficult to ascribe
      to a single aetiology. The various pathological changes that may affect liver
      allografts are selectively reviewed in relation to their likely time of
      occurrence after transplantation and their use for biopsy interpretation. Areas
      of controversy are highlighted.

PMID- 16892532
TI  - From stem cells to germ cell tumors and back.
AB  - Germ cell tumors originate from ovarian, testicular and extragonadal germ cells.
      Tumor stem cells can retain most of the features of germ cells and form seminomas
      or dysgerminomas or, transform into developmentally pluripotent embryonic stem
      cells and give rise to teratomas or teratocarcinomas. Similar tumors can be
      experimentally produced in mice from early mouse embryos transplanted to
      extrauterine sites. The malignant stem cells of teratocarcinomas, called in
      analogy with their human counterparts embryonal carcinoma (EC), can be isolated
      and grown in culture and or propagated indefinitely by isotransplantation in
      syngeneic inbred mice. When injected into the blastocyst, i.e., the embryonic
      environment from which they have been originally isolated, EC cells lose their
      malignancy and become benign, participating in the normal development of the
      injected blastocyst. Injection of EC cells into blastocysts has been used to
      generate transgenic mice. Developmentally pluripotent non-neoplastic embryonic
      stem (ES) cells can be produced from mouse blastocysts cultured in vitro. These
      cells are developmentally similar to EC cells. In contrast to EC cells, ES cells
      injected into adult mice do not produce teratocarcinomas but only teratomas.
      Similar ES cells were produced from human blastocysts cultured in vitro. Human ES
      injected into nude mice produce teratomas composed of various somatic tissues.
      Human ES cells resemble mouse ES cells, but differ from human EC cells. Like
      their mouse equivalents, human ES cells could be used for generating experimental
      models of various diseases and, hopefully, for cell therapy in not so distant
      future.

PMID- 16892533
TI  - [Advances and limitations of liver transplantation in Germany].
AB  - Orthotopic liver transplantation (OLT) is now an established therapy for end
      stage liver disease as well as acute liver failure. Improvements in surgical
      techniques, meticolous selection of transplant candidates and advances in
      immunosuppression have markedly increased patient and graft survial. The demand
      for organ grafts has continuously increased. Living donor organ transplantation
      omits the problem of organ shortage with prolonged waiting times for OLT and the
      likelihood of disease progression especially in tumor patients. Advanced liver
      disease related to chronic viral hepatitis is one of the primary indications for
      OLT worldwide. Combination therapy with hepatitis B immunoglobulin and lamivudine
      has been widely adopted as an effective prophylactic treatment regimen against
      recurrent HBV infection. Reinfection of the allograft is obligate in viremic post
      transplant patients with HCV infection. However the use of pegylated interferon
      in combination with ribavirin holds promise for delaying rapid progression of HCV
      infection in the allograft and the need for retransplantation. Recurrence of PBC,
      PSC and autoimmune hepatitis affects between 20 % and 30 % grafts at 10 years but
      appears to have little impact on long-term graft function and survival. In
      patients with hepatocellular carcinoma fulfilling strict selection criteria for
      OLT, 5 year survival rates of approximately 75% have been reported.

PMID- 16892534
TI  - [Pancreas transplant pathology: clinicopathologic and experimental findings].
AB  - 134 pancreas transplantations (113 simultaneous pancreas-kidney, 5 pancreas after
      kidney, 16 pancreas transplants alone) done in Rostock from VI/95 to III/04 were
      evaluated in respect to pancreas transplant lesions. Additionally, 36 pancreas
      specimen of Brown Norway rats experimentally transplanted into diabetic Lewis
      rats were examined. From 55 out of the 134 pancreas transplant patients, 122
      partly repeated pancreas graft specimen examinations were carried out
      morphologically. The principal lesions in the human pancreas transplants were
      acute (enzymatic) necrotizing transplant pancreatitis (41 samples), acute (13)
      and chronic (14) transplant rejection specimen as well as primary or secondary
      graft thrombosis (12 probes). 23 probes were zero-hour biopsies and 2 showed
      normal tissue. From 69 out of the 118 pancreas transplant patients with an
      additional kidney graft, a total of 159 renal transplant probes were examined.
      They showed the following lesions: acute tubular damage or acute renal failure
      (23), acute (56) or chronic (22) kidney graft rejection, acute tubular
      cyclosporine or FK 506 toxicity (53), and histologically normal graft tissue (8
      cases). As in other grafted organs, the changes occurring in the transplanted
      pancreas consist of varying lesions related and/or not related to pancreas
      transplant rejection. A concise classification and a reproduceable grading
      schedule are suggested for diagnostic, differential diagnostic, therapeutic, and
      prognostic purposes. Pancreatic rejection lesions can be classified according to
      a proposed Rostock '04 working classification of pancreas allograft rejection
      into three grades (I: mild, II: moderate, III: severe) both for acute and chronic
      pancreas rejection. There was no direct correlation of the findings in 21
      patients with simultaneously studied pancreas and renal transplant biopsies. In
      contrast to renal grafts, pancreatic rejection signs were often superimposed by
      acute transplantation pancreatitis with or without secondary graft thrombosis,
      nonenzymatic necroses or infection. Experimental acute pancreas transplant
      rejection in rats showed quite similar findings to human grafts and was also
      graded into three different acute rejection stages.

PMID- 16892535
TI  - [The spectrum of lymphoproliferations and malignant lymphoma after organ
      transplant].
AB  - Lymphoproliferative disease in patients with organ transplantation has
      increasingly been diagnosed in recent years. It is caused by immunosuppression
      after organ transplantion. A large percentage of these tumors is associated with
      Epstein-Barr virus infection. The classification differentiates between early
      lesions, polymorphic and monomorphic lymphoproliferations. Whereas the early
      lesions are often polyclonal, the remaining groups are mostly monoclonal.
      Polymorphic lymphoproliferative disease shows a wide spectrum of B-cell
      differentiation, whereas monomorphic proliferations resemble sproadic malignant
      lymphomas. The latter also show genetic abberations of the c-myc-, Ras-, p53- and
      Bcl6-genes. With reference to the germinal center reaction, posttransplant
      lymphoproliferations have to be assigned to the post-follicular activated B-cell
      type. While until 1991 only 2% of the cases of PTLD had an EBV-association, the
      EBV-associated PTLD have been frequently observed in recent times and presently
      constitute about 20% of the cases. EBV-negative PTLD constitute a negative
      prognostic factor. Posttransplant lymphomas might also represent a model for
      sporadic lymphoproliferative disease, that for example also occurs at elderly
      patients.

PMID- 16892536
TI  - [Polyomavirus nephropathy: pathogenesis, morphological and clinical aspects].
AB  - The polyoma-BK-virus strain was said to be "in search" of a disease. The search
      is finally over. Since the mid 1990's, when new third generation
      immunosuppressive drug regimens were introduced into the routine management of
      renal allograft recipients, the polyoma-BK-virus (allograft) nephropathy (BKN)
      has gained increasing clinical interest. BKN is currently the most common
      infection affecting renal allografts with a prevalence of 1% up to 10% reported
      in various transplant centers world-wide. It can lead to chronic allograft
      dysfunction and eventual graft loss in more than 50% of cases (observed in some
      institutions). BKN is most likely caused by the reactivation of latent BK viruses
      which enter under sustained and intensive immunosuppression into a productive and
      lytic replicative cycle. BKN is typically limited to the kidney transplant. It is
      histologically defined by the presence of intranuclear viral inclusion bodies in
      tubular and parietal glomerular epithelial cells. Different variants of
      polyomavirus inclusion bodies (types 1 through 4) and adjunct techniques
      [immunohistochemistry, electron microscopy and polymerase chain reaction (PCR)]
      that are used for proper characterization are described. Virally induced severe
      tubular injury is the morphologic correlate for the clinically observed allograft
      dysfunction. Special emphasis is placed on the pathogenesis leading from latent
      to productive BK-Virus infections and on the clinical and pathophysiological
      significance of different histological stages of BKN. Risk factors promoting
      disease as well as clues to diagnose BKN and concurrent acute allograft rejection
      are discussed. The pathologist's role in patient management using the detection
      of polyomavirus inclusion bearing decoy cells in the urine, plasma PCR analyses,
      and graft biopsies is highlighted.

PMID- 16892537
TI  - [Transplantation-associated infections].
AB  - Transplantation-associated infections are caused by an infected transplanted
      organ or the endogenic or exogenic environment of the recipient in a state of
      induced immunodeficiency. The best therapy would be to reconstitute the
      immunodeficiency, but this is usually impossible as it endangers the transplanted
      organ. Thus, a specific, standardised anti-infectious therapy is needed even in
      the absence of clearly identified micro-organisms [bacteria (in two thirds gram
      positive rods), parasites (in central Europe predominantly Toxoplasma), fungi
      (especially Candida spp. or Aspergillus spp.) or viruses (such as Parvovirus B19
      and Cytomegalovirus)]. Origins of infection (e.g., hygiene), types of infection
      (e.g., reactivation), typical localisations, diagnostic tools (e.g., blood
      cultures, antigenic tests, PCR, CT, advantages and disadvantages of antibody
      assays) and possible therapies are briefly discussed. The take home messages are
      to avoid economy measures in microbial diagnostics and to use CMV-seronegative
      donors whenever possible.

PMID- 16892538
TI  - [C4d: a pathogenetically relevant marker in kidney transplantation].
AB  - Antibody-mediated allograft rejection should be discriminated from cell-mediated
      rejection processes since these two distinct pathogenic mechanisms are likely to
      require different therapeutic approaches. The complement split product C4 d
      (although biologically inactive by itself) turned out to be a reliable diagnostic
      marker of antibody-induced complement activation in kidney allografts. In
      contrast to other organs like heart and bowel, there is no indication that
      ischemia/reperfusion injury might induce the classical pathway of complement
      activation in the kidney. Endothelial C4 d deposits in peritubular capillaries of
      transplanted kidneys are therefore robust indicators of antibody-mediated
      alloreactivity with potentially unfavourable outcome. The high efficiency of
      therapeutic strategies aimed at removing alloantibodies from the recipient's
      circulation (i.e. immunoadsorption and plasmapheresis) in cases of C4d positive
      rejection further underscores the important pathogenic role of antibodies in
      renal allograft rejection and the diagnostic relevance of endothelial C4 d
      deposits. C4 d deposits can also occur de novo in late allograft biopsies. Their
      association with basement membrane injury in peritubular capillaries and
      glomeruli, which are the hallmarks of chronic rejection, indicates a contribution
      of humoral immune reactions to chronic rejection. Due to the clinical relevance
      of humoral rejection and due to the fact that the latest update of the Banff
      classification introduced the pathogenically based subdivision of acute rejection
      into a cell-mediated and an antibody-mediated variant every renal allograft
      biopsy should be stained for C4 d. It is important to be aware that humoral and
      cellular rejection often occur simultaneously and that C4d deposits alone are not
      an unequivocal proof of humoral rejection that immediately requires treatment.

PMID- 16892539
TI  - [Pathology of lung transplantation and molecular aspects of pathogenesis].
AB  - Lung transplantation has become an established therapy for patients with a
      variety of end stage pulmonary diseases during the last twenty years. Many
      complications can affect the lung after transplantation, e.g. preservation
      related injury, mechanical complications of surgery, acute or chronic
      (obliterative bronchiolitis) rejection, infection, drug toxicity, recurrent
      disease, de novo disease, lymphoproliferative disorder. The regulation of tissue
      inflammation and repair mechanisms involving components of the immune systems
      depends on a number of cell-cell interactions. Today, our understanding of this
      pathogenetic and functional network is still at the beginning. The numbers of
      molecules and factors involved are still increasing. Technical progress has
      introduced a lot of new molecular techniques (e.g. PCR, cDNA Microarray etc.) for
      analysis of transplant reaction. Nevertheless assessment of lung allografts is
      usually by transbronchial biopsy and less commonly by thoracoscopic or open lung
      biopsy. A minimum of five fragments of alveolated lung parenchyma is required.
      Biopsies are examined by routine haematoxylin and eosin stain, connective tissue
      or elastic stains and further special stains, immunohistochemistry and molecular
      techniques will be performed if required. In examining biopsies from lung
      allografts three critical points to assess are: a. the presence or absence of
      acute rejection or b. chronic rejection (obliterative bronchiolitis), and c. the
      identification of infection. Interpretation of the histology requires knowledge
      of the clinical and microbiological results. New molecular techniques could help
      to elucidate the pathogenesis of transplant reaction and provide new insights to
      facilitate the clinical diagnostics of allograft pathology.

PMID- 16892540
TI  - [Pathology of small intestine transplantation].
AB  - Small bowel transplantation is being increasingly performed to treat patients
      with irreversible intestinal failure or short bowel syndrome. Worldwide
      approximately 100 transplantations are currently performed per year. Technical
      advances and new immunosuppressive strategies adopted during the last 10 years
      have significantly improved the quality of live and survival rate of the
      patients. The 5-year survival rate is currently around 60%. However, the
      procedure still bears significant live threatening risks. Mayor problems include
      surgical complications like anastomotic leakage or peritonitis, acute allograft
      rejection, systemic infection and in later stages loss of graft function due to
      chronic rejection. Acute rejection is common after intestinal transplantation. It
      may occur any time after transplantation and is seen in 50%-80% of the patients.
      The characteristic changes are enterocyte apoptosis in the crypts, cryptitis and
      mononuclear cell infiltration with activated lymphocytes. Severe cases may reveal
      ulcerations or even sloughing and widespread exfoliation of the epithelium and
      are almost invariably associated with graft loss. The histopathological
      abnormalities may be patchy and occur in grossly normal mucosa. Therefore,
      multiple biopsies should be generally sampled for histology. Acute rejection must
      be distinguished from infections in particular opportunistic viral infections
      caused by Cytomegalovirus (CMV) or Adenovirus as well as from Epstein-Barr virus
      related B-lymphocyte proliferations. Differential diagnosis also includes
      preservation injury and ischemia resulting in damage of the mucosal surface
      epithelium. Long-term graft function and survival are now increasingly determined
      by chronic rejection. The hallmarks of chronic rejection are obliterative
      arteriopathy of mesenterial vessels and progressive fibrosis of the transplant
      including its mesentery.

PMID- 16892541
TI  - [Left ventricular assist devices (LVAD): optional treatment alternative to
      cardiac transplantation?].
AB  - Left ventricular assist devices (LVAD) are used to "bridge" patients with end
      stage heart failure until transplantation of a donor heart can be performed
      ("bridge to transplantation"). However, LVAD support sporadically results in
      improved cardiac function, and heart transplantation is not necessary even after
      removal of LVAD in a subset of patients ("bridge to recovery"). Additionally,
      LVAD appears to be an optional treatment alternative to heart transplantation in
      patients with contraindication for organ replacement ("destination therapy"). The
      underlying process has descriptively been termed "reverse remodeling". The
      molecular basis remains incompletely understood at present, however, some
      mechanisms have been identified in the past. Alterations of several molecular
      pathways are involved in the development of chronic heart failure. Some of the
      pathways appear to be reversible and have been shown to be regulated by LVAD
      treatment. LVAD lead to lowered cardiac pressure and volume overload followed by
      decreased ventricular wall tension, reduction of cardiomyocyte hypertrophy,
      improved coronary perfusion and a decrease of chronic ischemia in the myocardium.
      Improved coronary flow and myocardial perfusion as well as decreased ventricular
      wall tension may serve as a possible explanation for changes of the molecular
      systems involved in the development of chronic cardiac insuffiency. This review
      focuses on the roles of apoptosis, heme-oxygenase-1 (HO-1), Metallothionein (MT)
      and the transcription factor NFkkappaB in chronic heart failure after mechanical
      circulatory support.

PMID- 16892542
TI  - [Clinical consequences of androgen receptor malfunction].
AB  - The androgen receptor (AR), the mediator of the effects of the male sex hormones
      testosterone and dihydrotestosterone, plays a crucial role in development of male
      sex and in the function of male sexual organs. Pathological alterations of AR
      structure and function are a major cause of androgen insensitivity in male
      pseudohermaphroditism and the accompanying deformations of genital organs, or
      result in spinal and bulbar muscular atrophy (SBMA). In addition, AR alterations
      that generate a hyperreactive receptor contribute to the development of
      resistance to hormone ablation therapy in prostate cancer. AR mutations found in
      patients with male pseudohermaphroditism usually are missens mutations that
      result in exchange of a single amino acid and cause complete or partial loss of
      function. The molecular change underlaying spinal and bulbar muscular atrophy is
      an extension of a poly-CAG repeat in the AR gene. The affected receptor tends to
      form aggregates, which damage motoneurons. Androgen ablation therapy puts
      prostate tumor cells under selection pressure that finally results in development
      of a hyperreactive androgen receptor that is activated under the conditions of
      therapy.

PMID- 16892543
TI  - [Genetic causes of male infertility].
AB  - 7% of all human males suffer from infertility. In at least 10% of these males
      infertility is due to genetic causes. Because modern reproduction techniques like
      ICSI (intracytoplasmic sperm injection) can help the couples to overcome
      infertility, it is mandatory to analyze underlying genetic causes of male
      infertility. If infertility in a male is due to a genetic defect, the risk of the
      respective couple for abortuses or malformed children is increased. The main and
      relevant causes for male infertility known to day are: numerical and structural
      chromosomal aberrations, meiotic defects, microdeletions in the region q11.21-23
      of the Y-chromosome, mutations in the gene for cystic fibrosis and genetically
      determined syndromes in which infertility is a symptom. The present knowledge
      concerning these genetic causes of male infertility is pointed out.

PMID- 16892544
TI  - From testicular biopsy to human embryo.
AB  - The aim of the study was to investigate the role of a testicular biopsy in the
      diagnosis and therapy of infertile men with a non-obstructive azoospermia.
      Overall, 70 testicular biopsies from infertile men were analysed. Samples were
      obtained by the "open testicular biopsy" method. After dissection, several pieces
      of the tissue were immediately immersed into the Sperm Prep Medium (Medi-Cult)
      and fixative (5.5% buffered glutaraldehyde). Tissue samples transported in Sperm
      Prep Medium were plunged into Sperm Freezing Medium (Medi-Cult) and were stored
      in liquid nitrogen for potential in vitro fertilization procedures. The tissue
      was also processed for semithin sections and transmission electron microscopy.
      Semithin sections from 8 infertile patients demonstrated regular testis structure
      and fully preserved spermatogenesis (control biopsies). In the remaining 62
      cases, spermatogenesis was impaired and a variety of pathological changes could
      be seen: disorganization and desquamation of spermatogenic cells, spermatid or
      spermatocyte "stop", spermatogonia only, "Sertoli cells only" or tubular
      fibrosis. However, in 65% of cases (despite the above mentioned changes of
      seminiferous epithelium) foci of preserved spermatogenesis could be detected.
      These cases were classified as "mixed atrophy" of seminiferous tubules. In 63% of
      infertile patients, a successful extraction of sperm from the biopsy could be
      performed. In azoospermic patients, histological analysis of testicular biopsy
      proved to be very useful in terms of diagnosis as well as therapy, i.e. for
      further in vitro fertilization procedures.

PMID- 16892546
TI  - [Prostatic adenocarcinoma--still a diagnostic problem].
AB  - Although the diagnosis of usual prostatic adenocarcinoma is not difficult by
      itself, problems may occur with diagnosis of small carcinomas in punch biopsies.
      Often small groups of suspicious glands are found with indistinct basal cell
      layer and lack of immunohistochemical expression of cytokeratin clone 34betaE12
      or p63. Despite disturbed architecture, carcinoma cannot be diagnosed without
      cytological criteria of malignancy, especially prominent nucleoli. This is not
      only a frequent problem in routine diagnostic slides but also in consultation
      cases. The consequence of the diagnosis "suspicious" is repeat biopsy after an
      interval of 6-12 months. Recently, a new marker for prostatic carcinoma an alpha
      methyl CoA-racemase (P504S) has been tested. P504S is overexpressed in carcinoma
      cells of the prostate. Together with negative basal cell marker P63 and positive
      reaction of P 504S this imunohistochemical combination confirms the diagnosis in
      35-45% of so called suspicious prostate biopsies. Facit: this group of patients
      have now a distinct diagnosis and must have a definite treatment without repeat
      biopsy.

PMID- 16892545
TI  - Do environmental factors play a role in the aetiology of carcinoma in situ testis
      and the testicular dysgenesis syndrome?
AB  - The hypothesis of the Testicular Dysgenesis Syndrome (TDS), first suggested in
      2001, propose that several disorders of the male reproductive system such as
      infertility, hypospadias, cryptorchidism and testicular cancer are all symptoms
      of TDS, which is most likely initiated during early foetal development, and may
      be provoked by external factors such as endocrine disruptors in addition to
      genetic predisposition. Testicular germ cell tumours (TGCTs), considered the most
      severe symptom of TDS, have increased in incidence during the last 60 years, to
      become the most common malignancy in young Caucasian men aged 17-45 years. TGCTs
      of young men originate from carcinoma in situ (CIS) cells. In the last few years,
      progress has been made identifying candidate genes involved in the neoplastic
      development of CIS, which may elucidate the timing of the initiation of CIS,
      currently thought to originate in foetal life from primordial germ cells or early
      gonocytes. Histological dysgenetic features are frequently seen in testes
      affected with the TDS components testis cancer or cryptorchidism. A TDS-like
      phenotype can be induced in male rats by in utero exposure to high concentrations
      of dibutyl phthalate (DBP) suggesting that ubiquitously present environmental
      endocrine disruptors may play a role in the aetiology of human TDS. So far, no
      animal model has been able to mimick all the symptoms of TDS including TGCTs
      although CIS-like cells have been found in a spontaneous testicular neoplasm in a
      rabbit.

PMID- 16892547
TI  - [Molecular pathology of prostate carcinoma. Academic playground or guide for
      diagnosis and therapy planning?].
AB  - No effective therapy exists for late-stage hormone-refractory prostate cancer. It
      would therefore be important to better understand the biological basis of
      prostate cancer progression. Since cancer is based on genetic alterations,
      detection of chromosomal changes can pinpoint critical genes and highlight
      mechanisms of cancer development and progression. Studies by comparative genomic
      hybridization (CGH) identified recurrent chromosomal aberrations across the
      progression from organ-confined to late-stage hormonerefractory cancer. These
      include frequent losses at 8p, 6q, 13q and 18q suggesting relevant tumor
      suppressor genes on these chromosomal arms. In contrast, several genes with
      oncogenic function are likely to reside on 8 q, which is frequently gained in
      advance stages. Importantly, there are several high-level amplifications in
      hormone-refractory and metastatic prostate cancers including Xq11-12, 1q21-25,
      8q21, 8q24, and 10q22 that may pinpoint to potent oncogenes. The high-level
      amplification of the androgene receptor at Xq11-12 is a paradigm as to how
      molecular cytogenetics can elucidate the molecular mechanisms of hormone
      refractory growth. Target gene identification of amplifications may lead to new
      diagnostic tools and therapies of advanced prostate cancer.

PMID- 16892548
TI  - [Lesions of the male breast].
AB  - Lesions of the male breast are rather rare. The most frequent lesion is
      gynecomastia followed by breast cancer. Gynecomastia is well known but male
      breast cancer is a rather rare tumor. It occurs in less than 1% of all cancers in
      men and of breast cancers. The mean age is high with a median of 68 years.
      Predisposing factors appear to be associated with hyperestrogenism such as
      testicular factors including maldescensus, orchitis and infertility. Other
      factors are Klinefelter, adipositas, diabetes mellitus and liver disease. In
      recent years an increased risk of male breast cancer has been reported in
      families with positive family history and in which BRCA2 mutations have been
      identified. Diagnostic procedures for male breast lesions should be the same as
      for the female breast. Underdiagnosis of male breast lesions is a frequently
      reported problem. Histology of male breast cancer differs in some aspects from
      female breast cancer. Male breast cancers are more frequently invasive ductal, G3
      and steroid hormone receptor positive. In case of intraductal cancer male lesions
      are more frequently papillary. Lobular carcinomas almost never occur. Prognostic
      factors for male breast cancer are similar to female breast cancer. For male
      breast cancer no randomised therapy studies are described. Therefore all therapy
      strategies are extrapolated from female breast cancer. The existing main
      therapeutic problem is undertreatment.

PMID- 16892549
TI  - [Chemokine directed homing of transplanted adult stem cells in wound healing and
      tissue regeneration].
AB  - A major challenge in stem cell biology is to study the underlying mechanisms of
      tissue specific homing and differentiation. Recent results suggest that bone
      marrow derived stem cells can give rise to multiple cell types. Because
      chemokines and chemokine receptors are associated with development,
      differentiation and homing of immune cells, we undertook efforts to study the
      chemokine receptor expression profile of human adult stem cells to identify their
      potential role in tissue specific homing prior to transdifferentiation. Using
      human bone marrow-derived stem cell lines, we could demonstrate functional
      chemokine receptor expression of various chemokine receptors. The expression of
      CXCR5 and CCR7, associated with secondary lymphoid organ homing as well as CXCR4
      and CCR10, involved in organ specific homing and CXCR3, CCR5 and CCR1, which are
      involved in inflammation events, suggested a role of chemokine receptors in
      tissue specific homing of stem cells. To proof the specific homing of stem cells
      in vivo, we used murine stem cell lines, stably introduced green fluorescent
      protein under control of CMV promotor into the cells and injected them
      intravenously into mice. We demonstrate the homing of these stem cells to
      lymphnode and thymus as well as mucosal tissue, while stem cells home exclusively
      to a site of lesion during wound healing and tissue regeneration. Our data
      suggest that chemokine biology may play a pivotal role in the homing of stem
      cells to specific tissues and niches prior to (trans)differentiation, while the
      homing changes during tissue damage and other adequate lesions.

PMID- 16892550
TI  - [Gastrointestinal stromal tumors carrying PDGFRalpha mutations occur
      preferentially in the stomach and exhibit an epithelioid or mixed phenotype].
AB  - AIMS: Most gastrointestinal stromal tumors (GISTs) carry gain-of-function
      mutations of the KIT gene encoding the receptor tyrosine kinase KIT. However, in
      a subset of GISTs no activating mutations are detectable in KIT. Recently,
      PDGFRalpha mutations have been identified as alternative oncogenic mechanism. We
      studied a panel of 100 GISTs for mutations in hot spot regions of KIT (exons 9,
      11, 13 and 17) and PDGFRalpha (exons 12 and 18) and compared the results with
      pathomorphological and immunohistochemical data. METHODS: DNA from formalin-fixed
      and paraffin-embedded tumor tissue was extracted after microdissection from
      serial sections. We performed single strand conformational polymorphism analysis
      and direct sequencing. RESULTS: We found PDGFRalpha mutations in 24 of 55 GISTs
      with wild-type sequence in exons 9, 11, 13 and 17 of KIT. All mutations were
      located in exon 18 of the PDGFRca gene which encodes the tyrosine kinase domain
      II. None of the 45 GISTs with detectable KIT mutation carried a mutation in the
      PDGFRalpha gene. Interestingly, all PDGFRalpha-mutated tumors were located in the
      stomach whereas GISTs with exon 9 and 13 KIT mutations occurred predominantly in
      the small bowel. Additionally, 21 of 24 GISTs carrying PDGFRalpha mutations
      displayed an epithelioid or mixed phenotype. In contrast, KIT-mutated GISTs
      exhibited almost always a spindled histology (38 of 45 cases). CONCLUSIONS: Our
      analysis provides evidence that GISTS represent distinctive entities with
      different genetic, biological and phenotypic features.

PMID- 16892551
TI  - [FISH analysis in the differential diagnosis of flat urothelial lesions using
      tissue microarrays].
AB  - AIMS: FISH technology offers an additional tool in the diagnosis of precancerous
      and malignant lesions of the urinary tract from cytological specimens. Here, we
      examined the relevance of chromosomal imbalance in flat urothelial lesions using
      FISH on paraffin-embedded tissue. In addition, the status of Her2/neu and STK15,
      a key molecule in the development of aneuploidy, was evaluated. METHODS: Flat
      lesions (normal urothelium, hyperplasia, reactive atypia, dysplasia and Carcinoma
      in situlCis) of 73 patients were analyzed in respect of chromosome 3, 7, 17
      polysomy, deletion of p16, status of HER2/neu and of STK15 by FISH (UroVysion,
      PathVysion, Vysis) and immunohistochemistry (HercepTest, DAKO) using tissue
      microarrays. The data were correlated with histology. RESULTS AND CONCLUSIONS:
      Aneusomy of at least one of the chromosomes usually correlates with the histology
      of carcinoma in situ or invasive tumor growth. Reactive atypias, rarely showing
      chromosomal imbalance, can be distinguished from Cis in the majority of
      investigated cases, but the FISH technique is not able to differentiate reactive
      atypia from mild dysplasia. About 30 % of the non-neoplastic lesions like
      urothelial hyperplasia and normal urothelium display polysomy of at least one
      chromosome in more than 20% of all cells, indicating an elevated risk towards a
      synchronous development of a higher dysplastic lesion (i.e. Cis). Polysomy of one
      of three investigated chromosomes (3, 7, 17) occurs randomly within all lesions.
      A deletion of the p16 locus is most frequently observed in aneuploid lesions.
      Altered Her2/neu expression patterns are frequently observed in malignant and
      dysplastic lesions but also in 25 % of the non-neoplastic lesions. An
      overexpression of Her2/ neu is found in 10-20% of invasive urothelial carcinomas
      and occasionally in Cis (5 %). However, the Her2/neu gene locus is not amplified
      in these samples. Gene amplification of STK15 was seen in tumors as well as in
      normal urothelium but it is still unclear whether it indicates an elevated risk
      towards the development of manifest urothelial tumors.

PMID- 16892552
TI  - [Multiprobe FISH for enhanced prediction of recurrent bladder cancer].
AB  - The early detection of recurrent urothelial cancer is a great challenge for both
      urologists and pathologists. Cytology is a sensitive and highly specific tool for
      the diagnosis of high-grade bladder cancer and carcinoma in situ, but is not
      reliable in low-grade tumors. Therefore, cystoscopy has remained the gold
      standard for surveillance after resection of bladder cancer. Recent data suggest
      that multi-target fluorescence in situ hybridization (FISH) can markedly improve
      the sensitivity of urinary cytology. The goal of this study was to investigate
      the utility of the recently developed FISH assay Uro-Vysion for the prediction of
      recurrence during surveillance. 134 bladder washes obtained during a negative
      follow-up cystoscopy from 127 patients were analyzed. Positive cytology was
      strongly associated with subsequent recurrence, emphasizing the importance of
      conventional cytology for bladder cancer surveillance. A positive UroVysion FISH
      test significantly predicted recurrence when cases with rare tetraploic cells
      were considered as negative. Taken together, both cytology and FISH help to
      better determine the risk of bladder cancer recurrence in order to establish more
      individualized follow-up schemes.

PMID- 16892553
TI  - [HDMX amplification and high levels of HDMX-S splice variant are correlated with
      a poor prognosis in soft tissue sarcomas].
AB  - The aim of this study was to determine the amplification status of the HDMX gene
      and the expression of the HDMX mRNA particularly that of the HDMX-S splice
      variant in soft tissue sarcomas (STS). We show that the HDMX gene is amplified in
      27% of STSs, which was associated with a worse prognosis (RR = 2.8, p = 0.03). We
      have also found that the transcript of the HDMX-S variant was predominant in a
      subset of (14%) of tumor samples, which was correlated with a significantly
      decreased overall survival time (15 vs. 53 months, p < 0.0001, log-Rank-test) and
      with a 9-fold-increased risk of tumor-related death (p < 0.0001). There was no
      correlation between the HMDX gene amplification and the HDMX-S splice variant
      overexpression. In summary, our data indicate that both the overexpression of the
      HDMX-S transcript, as well as, the HDMX gene amplification are important
      prognostic markers for STS.

PMID- 16892555
TI  - ["Dieser im besten Sinne selbstgemachte Mann..."--Heinrich Schliemann's lifework
      from Rudolf Virchow's point of view].

PMID- 16892554
TI  - [Prediction of response to neoadjuvant chemotherapy in Barrett's carcinoma by
      quantitative gene expression analysis].
AB  - The potential of gene expression profiles to predict the response to neoadjuvant
      chemotherapy in patients with advanced adenocarcinoma of the esophagus was
      analyzed. Paraffin-embedded endoscopic esophageal tumor biopsies of 38 patients
      with advanced esophageal adenocarcinoma (Barrett's adenocarcinoma) were included.
      All patients underwent two cycles of cisplatin and fluorouracil (5-FU) therapy
      with or without additional paclitaxel (taxol) followed by abdominothoracal
      esophagectomy. RNA expression levels of 5-FU-metabolism associated genes
      thymidylate synthase (TS), thymidine phosphorylase (TP), dihydropyrimidine
      dehydrogenase (DPD), methylenetetrahydrofolate reductase (MTHFR), MAP7, ELF3, as
      well as of platinum and taxane associated related genes caldesmon, excision cross
      complementing genes (ERCC1 and ERCC4) HER2-neu, DNA damage-inducible gene 45
      (GADD45) and multidrug resistance genes (MDR1, MRP1) were determined using real
      time RT-PCR. Expression levels were correlated with the histopathological
      response to chemotherapy assessed in surgically resected specimens. Responding
      patients showed significantly higher pretherapeutic expression levels of MTHFR (p
      = 0.012), Caldesmon (p = 0.016), MRP1 (p = 0.007) and MDR1 (p = 0.025). In
      addition, patients with high pretherapeutic MTHFR and MRP1 levels had a survival
      benefit after surgery (p = 0.013 and p = 0.015, respectively). Additionally,
      intratumoral heterogeneity of gene expression of selected genes (TP, DPD, MTHFR,
      HER2-neu, Caldesmon, ERCC4, MRP1) was additionally verified in 9 untreated
      Barrett's adenocarcinoma by examination of 5 distinct tumor areas and was
      observed in 12.7% (5.6%-23.5%, CI 95%) of all cases analyzed. Our results
      indicate that determination of mRNA levels of a few genes may be useful for the
      prediction of the success of neoadjuvant chemotherapy in individual cancer
      patients with advanced adenocarcinoma of the esophagus.

PMID- 16892556
TI  - [Rhabdomyosarcoma development in Trp53/fos mutant mice: tumor suppressor
      functions of the Fos protooncogene].
AB  - Rhabdomyosarcoma is the most common soft tissue sarcoma in children, yet the
      genetic changes causing this disease are poorly understood. The Fos protein, a
      major component of the AP-1 transcription factor, is essential for osteoclast
      differentiation, acts as an oncogene, potentiates transforming signals and
      controls invasive growth and angiogenesis during tumor progression. To
      genetically investigate a potential interaction between the p53 and Fos pathways,
      Trp53/Fos double knock-out mice were generated. These mice develop highly
      proliferative and invasive rhabdomyosarcomas of the facial and orbital regions
      with more than 90% penetrance at 6 months of age. Expression of Fos in Trp53/Fos
      mutant rhabdomyosarcoma cell lines established from primary tumors is associated
      with enhanced apoptosis and downregulation of Pax7 expression. Our results show
      that Trp53/Fos double knock-out mice recapitulate major aspects of human
      rhabdomyosarcoma development and therefore provide a mouse model for the human
      disease. Furthermore, this study identifies a novel and unexpected tumor
      suppressive function of the Fos proto-oncogene.

PMID- 16892557
TI  - Reappraisal of thromboangiitis obliterans--a pathological contribution.
AB  - Thromboangiitis obliterans (TAO), the Winiwarter-Buerger disease, is a
      vasoocclusive disease of unknown etiology which typically affects medium-sized
      extremital vessels of young male smokers. While the diagnosis of TAO is largely
      based on patients' presentation and clinical criteria, pathological substrates
      have been poorly defined and repeatedly disputed. Comparing the histology and
      immunohistochemistry of TAO especially with those of arteriosclerosis obliterans
      (ASO) and thromboembolism in two larger studies, we recently identified several
      features with significant meaning for the differential diagnosis. The unique
      tissue appearance of TAO is in favor of a general disorder of minute vessels
      indicating periarteritis rather than pure endarteritis, whereas an inflammatory
      reaction directed to the internal elastic lamina corresponds with the severity of
      disease. Since TAO or its syndromic equivalent is probably more common than
      currently diagnosed, the presented pathological criteria may help to identify
      latent cases, the overlap with ASO, and untypical organ involvement of TAO.

PMID- 16892558
TI  - [Role of the class II tumor suppressor gene maspin in thyroid carcinogenesis].
AB  - The presented study was aimed to investigate new mechanisms of carcinogenesis in
      thyroids at the molecular level and to find potential protein markers involved in
      the initiation of the different histological subtypes of thyroid carcinoma. For
      this, we performed differential proteome analysis on primary cultured thyrocytes
      and transformed thyrocytes derived from 238Pu alpha-particle irradiation using
      two-dimensional electrophoresis (2-DE) and peptide mass fingerprinting (PMF) with
      matrix-assisted laser desorption/ionisation-time of flight mass spectrometry
      (MALDI-TOF MS). Proteome analysis identified a strong upregulation of maspin, a
      serine protease inhibitor and class II tumor suppressor, in irradiated
      thyrocytes. To clarify the role of maspin in thyroid carcinogenesis, we searched
      for mRNA/protein expression in 30 normal (tumor-free) thyroid tissues, 35
      follicular adenomas, 68 papillary carcinomas, 38 follicular carcinomas, 25 poorly
      differentiated carcinomas, and 34 undifferentiated carcinomas and compared the
      results with maspin promoter methylation status, p53 expression,
      clinicopathological data and prognosis. Maspin expression was detectable in 48 of
      68 papillary carcinomas exclusively. There was a low methylation rate of 28% in
      papillary carcinomas in contrast to the other tissues (89-100%). p53 was positive
      in 2% of maspin positive cases, and in 80% of maspin negative cases. After 110
      month follow-up 83% of the maspin positive patients had recurrence-free disease,
      whereas only 40% of the maspine negative patients were recurrence-free. Our data
      suggest: (1) maspin expression is a special feature of papillary thyroid
      carcinomas, (2) promotor methylation-caused maspin repression plays a major role
      in gene balance and in the process of tumor determination, (3) maspin protein
      possibly functions as a clinically relevant inhibitor of tumor progression, (4)
      our data delivers the hints for a p53-depentent regulatory pathway of the maspin
      protein in human cancer.

PMID- 16892559
TI  - [The overexpression of NCAM (CD56) in human hearts is specific for ischemic
      damage].
AB  - The main reason for myocardial dysfunction is chronical myocardial ischemia.
      Recently we could show, that NCAM (CD56), a neural cell adhesion molecule and
      member of the immunoglobuline superfamily, and the transcription factor AML1
      (RUNX1) are overexpressed in chronic ischemic human heart failure compaired to
      normal hearts. Here we demonstrate, that the overexpression of NCAM (CD56) is
      specific for ischemic damage as compaired to other heart diseases including
      congestive cardiomyopathy, hypertrophic obstrutive cardiomyopathy, myocarditis
      and sarcoidosis. Concerning the transcriptional regulation of NCAM (CD56) by AML1
      (RUNX1) we isolated 3 novel isoforms of AML 1 (RUNX1) with different
      transactivating function, that might be a regulatory element of the NCAM (CD56)
      overexpression in chronical myocardial ischemia.

PMID- 16892560
TI  - [List of member: German Society for Pathology].

PMID- 16892562
TI  - A medical practitioner's perspective.

PMID- 16892561
TI  - The South African declaration on AIDS.

PMID- 16892563
TI  - Fourth International Workshop on the Oral Manifestations of HIV: 4-7 July 2000 in
      the Kruger National Park.

PMID- 16892564
TI  - The impact of research upon dentistry.

PMID- 16892565
TI  - Prevention of bacterial endocarditis.

PMID- 16892566
TI  - HIV infection and oral health care in South Africa.
AB  - This study determined the knowledge, attitude and practice of oral health care
      workers in public clinics in South Africa towards HIV/AIDS and investigated the
      implementation of infection control measures. A total of 727 questionnaires were
      distributed to dentists, dental therapists, oral hygienists and chairside
      assistants in the public dental clinics of 9 provinces, of which 276 were
      returned from 8 provinces, giving a response rate of 38%. The questionnaire
      covered demographic factors and assessed issues such as knowledge, infection
      control practices, continuing education, legal, ethical and psychosocial issues
      and available support for HIV/AIDS. The common oral manifestations seen by
      respondents were candidiasis, acute necrotising ulcerative gingivitis (ANUG),
      hairy leukoplakia and Kaposi's sarcoma. Of the 174 who had a previous HIV test,
      48% were for insurance purposes and 21% for post-needle-stick injury. Over 10% of
      the respondents indicated that gloves were not available at all, that there was
      an inadequate supply of water, and that there was no autoclave in their clinic.
      Nearly 50% of the clinicians had not had hepatitis B vaccination in the last 3
      years. Fifteen respondents (5.4%) were not willing to treat HIV-positive
      patients. Only 48% had access to a written post-exposure management protocol and
      post-exposure medication was available to only 36.6%. The vast majority of the
      respondents clearly expressed a need for additional education on HIV/AIDS. The
      study demonstrated a need to add knowledge, enhance personal skills and improve
      the application of universal precautions.

PMID- 16892567
TI  - Oral soft-tissue manifestations as presenting symptom/sign of HIV infection.
AB  - This prospective study reports oral manifestations noted in 17 patients as the
      first indications of HIV infection, and serves to remind health workers of the
      need to examine the oral soft tissues thoroughly. This study also demonstrated
      that other HIV-associated oral lesions are often seen in addition to the
      presenting symptom or sign, which was highly variable and not lesion-specific.
      Appropriate management of the patient after recognition of the significance of
      these signpost oral lesions could affect quality of life, influence the course of
      the disease and reduce the risk of transmission. Dentists need to be alert to and
      knowledgeable about these lesions which will become more prevalent as the numbers
      of HIV-positive persons increase in South Africa.

PMID- 16892568
TI  - The treatment of oral candidiasis in a cohort of South African HIV/AIDS patients.
AB  - The purpose of this study was to determine the extent and outcome of antifungal
      treatment in HIV/AIDS patients. Data obtained from patients attending a hospital
      based, semi-urban comprehensive care HIV clinic, were retrospectively analysed.
      The clinic serves patients from urban, semi-urban and rural communities. A total
      of 751 confirmed black heterosexual HIV/AIDS patients received routine oral
      examinations and surveillance swabbing for oral yeast culture. Patients received
      nystatin solution as prophylaxis, miconazole for clinically detectable oral
      candidiasis and only in severe cases or cases of chronic candidiasis were they
      treated with either fluconazole or itraconazole. Treatment was regarded as
      successful when there was an absence or resolution of clinical lesions of oral
      candidiasis. Nystatin prophylaxis was prescribed to 7.9% of patients, miconazole
      treatment to 9.7% and 3.5% received fluconazole. Of the 60 patients who received
      nystatin prophylaxis, 40 (66.6%) had clinically detectable candidiasis. A
      negative statistical correlation was found between nystatin prophylaxis and
      clinically detectable candidiasis. Of 72 patients who received miconazole
      treatment, only 3 failed to respond. Eleven of the 27 patients who received
      fluconazole treatment did not return for follow-up visits. In the remaining 16
      patients there was no recurrence of clinical symptoms during the following 3 - 24
      months after treatment with fluconazole. It is concluded that nystatin
      prophylaxis proved not to be effective under these particular clinical
      circumstances. Resistance to azole antifungal medication is not yet a problem in
      this black heterosexual group of South African HIV/AIDS patients.

PMID- 16892569
TI  - Current concepts in HIV/AIDS.

PMID- 16892570
TI  - HIV/AIDS - the evolving pandemic and its impact on oral health in sub-Saharan
      Africa.
AB  - This review provides an update on HIV/AIDS based on a literature search (1989
      1999) in respect of its epidemiology and oral manifestations in sub-Saharan
      Africa. The African epidemic is unique in its heterosexual spread, high
      prevalence in men, women and children, rapid rise in young women and risk of
      vertical transmission. Viral subtypes A and D predominate in Africa, subtype C in
      South Africa and subtype E in Central Africa. The pandemic is fueled by endemic
      poverty, malnutrition, gender inequality and sexual and cultural practices. Oral
      lesions may frequently be the initial presenting signs of HIV infection, early
      clinical features, predictors of progression of disease and may be useful in
      staging and classification. Health care workers require training to understand,
      diagnose, manage and research these manifestations.

PMID- 16892571
TI  - Are the oral manifestations associated with HIV infection really relevant to the
      practising South African dentist? A comparative analysis of oral HIV studies in
      South Africa.
AB  - This comparative analytical review of oral HIV in South Africa, Africa and the
      West shows that relatively little work has been done on the African continent in
      this field of study. Direct epidemiological comparisons of these studies with
      each other are difficult but were made between these regions for overall
      prevalence values, mode of transmission and individual lesion presentation
      (candidiasis, oral hairy leukoplakia, periodontal disease, Kaposi's sarcoma,
      salivary gland disease, oral ulcers and other lesions). Apparent differences
      exist between the reported prevalence values of oral candidiasis, periodontal
      disease, Kaposi's sarcoma and tuberculous ulcers, the significance of which is
      uncertain. There is a need to standardise research methodologies. This would
      enable appropriate comparisons to be made and a better understanding of the
      implications of the oral HIV disease process in South Africa and elsewhere on the
      continent.

PMID- 16892572
TI  - HIV- periodontal disease. A review of research prospects: a South African and
      Namibian perspective.
AB  - In the course of infection by the human immunodeficiency virus (HIV) typical
      changes of inflammatory periodontal disease may arise. It is estimated that the
      prevalence of HIV-associated periodontal diseases may vary between 5% and 12% and
      can occur in both symptomatic and asymptomatic individuals. These oral lesions
      are very important either as an initial presentation of AIDS or as a sign of
      established immunosuppression. For the patients, HIV-associated periodontal
      diseases can cause pain, severe discomfort and a decreased quality of life. It is
      therefore important, from both diagnostic and therapeutic aspects, for dentists
      to be able to distinguish and diagnose HIV-associated periodontal diseases as
      early recognition and treatment of these oral lesions may reduce morbidity and
      allow more comfort to the patient during progression of the disease. This paper
      reviews the current international and regional status of HIV-associated
      periodontal diseases and highlights research prospects in countries such as
      Namibia and South Africa, to further analyse periodontal diseases in HIV/AIDS
      patients.

PMID- 16892573
TI  - Are you positive?

PMID- 16892575
TI  - Birdwatching - great therapeutic value.

PMID- 16892574
TI  - Update on infection control.
AB  - Infection control is a dynamic and ever-changing subject and all dental staff
      should be kept aware of the most up-to-date procedures required to prevent the
      transmission of infection and should understand why these procedures are
      necessary. Regular monitoring and updating of all procedures in the light of new
      scientific evidence is necessary and all new staff must be trained in infection
      control procedures prior to working in the surgery. A practitioner who is
      routinely following an appropriate infection control policy, including the use of
      techniques and products of proven efficacy (perhaps through accreditation), is
      better placed to refute allegations arising in the course of civil litigation,
      health and safety at work prosecution, complaints and disciplinary procedures, or
      investigations by the GDC.

PMID- 16892577
TI  - [Effect of sodium fluoride on the activity of sorbitol dehydrogenase in plasma
      and liver of rabbits with experimental atherosclerosis].
AB  - This study was done in rabbits placed on a low-cholesterol (0.5 g%) and high
      cholesterol (2.0 g%) diet to induce experimental atherosclerosis. The intake of
      fluorine in the form of NaF in water was 3 mg F(-)/kg b.w./24 h. The activity of
      sorbitol dehydrogenase (SDH) was increased in plasma and decreased in the liver
      of rabbits on the high-cholesterol diet and in animals simultaneously exposed to
      NaF in water. Two months of the low-cholesterol diet produced an increase in SDH
      activity in plasma as a direct consequence of exposure to fluoride in the diet
      and presumably caused by accumulation of fluoride in the liver.

PMID- 16892576
TI  - [Fluorine as a factor in premature aging].
AB  - The use of fluorine compounds in various areas of medicine, particularly in
      dentistry, as well as in agriculture and industry became very popular in the
      second half of the 20th century. Fluorine owed this widespread acceptance to
      observations that its compounds stimulate ossification processes and reduce the
      prevalence of caries. Unfortunately, growing expectations overshadowed the truth
      regarding interactions of fluoride on the molecular level. The fact was often
      ignored that fluoride is toxic, even though laboratory data stood for a careful
      approach to the benefits of usage. Excessive exposure to fluoride may lead to
      acute poisoning, hyperemia, cerebral edema, and degeneration of the liver and
      kidneys. Acute intoxication through the airways produces coughing, choking, and
      chills, followed by fever and pulmonary edema. Concentrated solutions of fluorine
      compounds produce difficult to heal necrotic lesions. In spite of these dramatic
      symptoms, acute intoxications are relatively rare; the more common finding is
      chronic intoxication attributable to the universal presence of fluorine compounds
      in the environment. The first noticeable signs of excessive exposure to fluoride
      in contaminated water, air, and food products include discolorations of the
      enamel. Dental fluorosis during tooth growth and loss of dentition in adulthood
      are two consequences of chronic intoxication with fluorine compounds.
      Abnormalities in mineralization processes affect by and large the osteoarticular
      system and are associated with changes in the density and structure of the bone
      presenting as irregular mineralization of the osteoid. Fluorine compounds also
      act on the organic part of supporting tissues, including collagen and other
      proteins, and on cells of the connective tissue. These interactions reduce the
      content of collagen proteins, modify the structure and regularity of collagen
      fibers, and induce mineralization of collagen. Interactions with cells produce
      transient activation of osteoblasts, stimulate fibroblasts to produce
      collagenase, and trigger toxic reactions in osteocytes and chondrocytes of
      trabecular bone. Growing deformations of the skeleton reduce mobility and result
      in permanent crippling of the patient. Fluoride increases the mass of non
      collagen proteins such as proteoglycans and glucosaminoglycans, accelerating skin
      aging even though protein biosynthesis is generally suppressed. The final outcome
      includes progressive vascular lesions and disorders of energy metabolism in
      muscles. In conclusions, the use of fluoride, particularly by dentists and
      pediatricians, must be controlled and adapted to individual needs. It is worth
      remembering that fluoride: is the cause of disability due to bone deformations
      and abnormalities in the musculoskeletal system; reduces the incidence of caries
      but do not protect against tooth loss; exerts an adverse effect of metabolic
      processes in the skin; accelerates calcification of vessels and thus reduces
      their elasticity; inhibits bioenergetic reactions, in particular oxidative
      phosphorylation, reducing physical activity of muscles. These findings suggest
      that fluorine may be yet another factor in accelerated aging and revive the
      dispute started more than two and half thousand years ago whether aging is a
      physiologic or pathologic process. The understanding of factors modifying the
      process of aging is the basis for preventive measures aimed at extending life and
      maintaining full psychosocial activity.

PMID- 16892579
TI  - [Effect of sodium fluoride on ectopic induction of bone tissue].
AB  - Fluoride is a very potent bone stimulating factor. The aim of the study was to
      assess the influence of sodium fluoride on bone formation and resorption in the
      process of experimental ectopic bone formation. Ectopic bone formation was
      induced 10 days after the start of treatment. Two groups of 15 rats each, study
      and control, were formed. The study group received 100 ppm sodium fluoride in
      water. Devitalised bone matrix grafts were implanted intramuscularly in two
      thorax regions. Eight weeks later the ossicles were removed and prepared without
      decalcification for histomorphometric analysis. Osteoid perimeter (O.Pm) and
      osteoblast number (N.Ob) were higher in the study as compared to the control
      group (42.24 +/- 4.14 vs. 12.18 +/- 2.89; p < 0.01 and 26.07 +/- 3.26 vs. 10.24
      +/- 1.39; p < 0.01, respectively). Osteoclast number (N.Oc) was increased in the
      study group (4.31 +/- 0.40 vs. 2.53 +/- 0.31; p < 0.01). No significant
      differences in bone area (B.Ar/T.Ar) were found (19.36 +/- 2.26 vs. 18.67 +/-
      3.71). It was concluded that sodium fluoride not only increases osteoblast
      activity but also stimulates bone resorption in bone matrix grafts.

PMID- 16892578
TI  - [Dietary and hygienic aspects of fluoride exposure in pregnant women].
AB  - The study was undertaken to assess the exposure of pregnant women to fluoride on
      the basis of diet preferences and hygienic habits revealed with a questionnaire.
      The group included 59 women aged 22-39, living in a large urban agglomeration.
      Questions concerned sources of fluoride such as diet (tap water, tea, fish,
      poultry), use of fluoride-containing preparations for oral hygiene and substances
      containing fluoride for additional prophylaxis. The oral health status was
      clinically examined and caries intensity was assessed with the mean DMF-t index.
      According to the clinical examination, the mean DMF-t index was 13.64 and ranged
      from 1 to 23. Consumption of tap water averaged 0.73 L (max. 2.5 L), including
      0.55 L (max. 2.5 L) of tea. Poultry was a regular part of the diet in only 14 of
      the respondents (24%) and only 3 (5%) sporadically (once a week) ate ocean fish.
      All the respondents used toothpaste containing fluoride, but only 15.3% applied
      professional prophylaxis with fluoride preparations. As far as the diet is
      concerned, individual differences in the intake of fluorides were significant.
      Interestingly, despite the declared everyday use of fluorine-containing
      toothpaste, the caries intensity index was rather high, suggesting the need for
      special dental care in this group of patients.

PMID- 16892580
TI  - [Concentration of fluoride in mixed saliva of patients with end-stage renal
      disease undergoing renal replacement therapy].
AB  - This study was carried out on 48 patients with ESRD undergoing hemodialysis
      treatment (29 males and 19 females, mean age 50.8 years) and renal
      transplantation (15 females and 33 males, mean age 42.2 years). The results were
      compared with a group of 44 healthy persons (23 females and 21 males, mean age
      49.5 years). The aim of our investigation was to examine the content of fluoride
      in the mixed unstimulated saliva of the patients undergoing renal replacement
      therapy and in the control group of healthy persons. We studied the influence of
      hemodialysis on saliva fluoride levels. Saliva samples were collected by the
      spitting method according to Navazesh. Samples were collected before and after
      hemodialysis session and once in graft recipients and controls. Fluoride
      concentrations were determined with an Orion fluoroselective electrode model 96
      09. The fluoride level in healthy persons was 4.92 +/- 2.30 micromol/L. Before
      hemodialysis, the mean fluoride level was 9.63 +/- 3.90 micromol/L and decreased
      significantly to 7.52 +/- 2.71 micromol/L after hemodialysis (p < 0.0001). Saliva
      content of fluorides in patients before and after hemodialysis was significantly
      higher than in healthy subjects and kidney graft recipients (p < 0.0001). There
      was no significant difference in fluoride concentration between patients after
      kidney transplantation and controls. The results suggest the need for individual
      fluoride supplementation in chronically hemodialysed patients.

PMID- 16892582
TI  - [Activities of some enzymes and concentration of ammonia in serum of rats with
      fluoride hyperglycemia].
AB  - The study was done in 30 one-month-old Wistar FL rats divided into one control
      and two study groups of ten animals each. Hyperglycemia was induced with sodium
      fluoride in water at a concentration of 50 or 100 mg/L during four months.
      Control animals received distilled water. We observed significantly (p < 0.05)
      reduced activities of aspartate aminotransferase (by 22.8%) and malic
      dehydrogenase (by 10.9%) in the group exposed to 100 mg F(-)/L. No pathological
      changes were revealed in the pancreas of exposed animals.

PMID- 16892581
TI  - [Effect of 10-15% carbamide peroxide on enamel fluoride concentration in vital
      bleached teeth].
AB  - The objective of the study was to evaluate the concentration of fluoride in human
      enamel before and after bleaching using 10-15% carbamide peroxide and after
      application of the fluoride varnish. Microsamples of enamel were collected using
      acid biopsy and the concentration of fluoride in the superficial and underlying
      layer was assayed. No significant differences were observed in the concentration
      of fluoride in both layers of enamel before and after bleaching as well as after
      varnish application. Bleaching with 10-15% carbamide peroxide has no influence on
      the concentration of fluoride in enamel.

PMID- 16892583
TI  - [Living conditions of deer in the provinces of Western Pomerania and Lubuskie as
      revealed by mandibular content of fluoride, calcium, and magnesium. I. Inter
      relations between fluoride, calcium, and magnesium content in mandible].
AB  - The south-western regions of Poland are more exposed to industrial emissions
      containing fluorine than eastern and northern regions. Fluoride is known to
      accumulate in hard tissues of animals and humans. This paper describes the
      content of fluoride in mandibles (lower jaws) of deer from two provinces: Western
      Pomerania and Lubuskie. The fluoride content in lower jaws of deer from Lubuskie
      was statistically higher compared with fluoride content in Western Pomerania. We
      concluded that the living conditions of animals in Western Pomerania are more
      favorable than in Lubuskie. When the concentration of fluoride in bone becomes
      too high, mineralization defects can occur causing major loss in mechanical
      resistance despite an increase in bone mass.

PMID- 16892585
TI  - [Seasonal fluctuations in fluoride content in waters of the Warta oxbow lake in
      Lubon].
AB  - Studies were carried out in 2002-2003 at the Department of Inland Fishing and
      Aquaculture, Agricultural University of Poznan, on seasonal fluctuations in
      fluoride content in waters of the Warta oxbow lake in Lubon (52 degrees 19' N, 16
      degrees 53' E). This reservoir has been loaded during several decades with
      fluorine compounds, originating from the deposits of post-crystallization lye of
      aluminum fluoride and fluorosilicic acid. The greatest amounts of fluorine
      compounds were deposited in the bottom sediments in the deepest part of the
      reservoir. On the basis of these two-year observations it was concluded that the
      concentration of fluoride in water is subject to significant variations (between
      1.0 and 6.2 mg F(-)/L). The lowest fluoride concentration in water was recorded
      during vernal circulation. On the other hand, the highest values were found in
      the bottom water layer during the summer stagnation. Seasonal fluctuations in
      fluoride content in waters of the Warta oxbow lake were closely connected with
      mineralization in the bottom sediment as revealed by oxygen deficiencies in the
      bottom water layer.

PMID- 16892584
TI  - [Living conditions of deer in the provinces of Western Pomerania and Lubuskie as
      revealed by mandibular content of fluoride, calcium and magnesium. II. Detailed
      statistical analysis with the statistica neural networks software].
AB  - Animals from areas contaminated by industrial emissions containing fluoride may
      accumulate it predominantly in hard tissues. The stable composition of the
      mandible makes it suitable for the study of accumulation of fluorides and other
      elements (Mg, Ca). It is also possible to determine the extent of pollution with
      fluorine compounds around industrial plants and to reveal some of the features of
      the natural habitat of wild animals. We applied the advanced technique of neural
      networks to investigate the simultaneous influence of multiple parameters on the
      accumulation of fluorine, magnesium, and calcium in the mandible of deer and
      possible interactions between these elements. The first step involved the
      generation of a neural network. In the present work, networks were created with
      the Intelligent Problem Solver (IPS). Input data were divided into three sets.
      One was used for training (Tr) of the network, another for validation (Ve) and
      control over the training process and the last one for testing (Te). Network
      quality was checked with the following parameters: Data Mean--average value of
      variable; Data SD--standard deviation of variable; Error Mean--average value of
      error; Abs. Mean--average error modulus; Error SD--standard deviation of error;
      SD Ratio--ratio of standard deviation of error to standard deviation of variable
      (Error SD/Data SD); Correlation--Pearson's correlation coefficient. For the model
      to be satisfactory, Pearson's correlation coefficient should be close to 1. In
      the case of complex problems with an unclear influence of parameters on the
      process, an analysis of parametric sensitivity must be performed. This task was
      accomplished automatically with the computer program. It was found that the
      effect of the same parameters on the accumulation of fluorine, magnesium and
      calcium varied. The results suggest interactions between the examined elements.

PMID- 16892586
TI  - [PH values and fluoride levels in some tea brands].
AB  - The purpose of the study was to determine the pH and fluoride levels in selected
      commercial tea brands sold in supermarkets and to evaluate the importance of tea
      as a dietary source of fluorine. Thirty six different brands and types of tea in
      bags were evaluated. In order to prepare the tea, one bag of tea (1.5-2 g) was
      covered with 200 mL of boiling deionized water for 3 minutes. The pH was measured
      with a pH-meter and fluoride concentration was determined with an ion-selective
      electrode (Orion 9609). pH values of the tea infusions ranged from 3.85 to 6.45
      (mean 5.24) and fluorides from 0.12 ppm to 8.33 ppm (mean 1.32 ppm). Thus, the
      individual intake of fluorine is estimated at 0.66 mg per 500 mL of tea. The
      results confirm that regular consumption of tea is an important dietary source of
      fluorine.

PMID- 16892587
TI  - [Release of fluoride ions into saliva from some dental materials].
AB  - The aim of the study was to evaluate fluoride release from dental materials:
      resin composites--Tetric Ceram and Degufill Mineral, fissure sealants--Conseal F
      and Admira seal, compomer--Freedom and glass-ionomer cement--Vitremer. Release to
      the patient's unstimulated mixed saliva was studied after treatment with the
      material. The study group comprised 72 patients and fluoride concentrations were
      measured with an ion-selective electrode (Orion). The following release of
      fluoride in decreasing order was found: Vitremer (6.03 microM), Degufill Mineral
      (2.79 microM), Teric Ceram (2.54 microM), Freedom (2.52 microM), Admira seal
      (1.85 microM) and Conseal F (1.80 microM).

PMID- 16892588
TI  - [Effect in vitro of environmental parameters on the release of fluoride ions from
      some materials used in dentistry].
AB  - The aim of this in vitro study was to evaluate the influence of calcium ions and
      pH on fluoride release from selected dental materials. The materials studied
      included a resin composite (Te-Econom), fissure sealant (Conseal F) and compomer
      (Freedom). Samples were placed for 7 days in artificial saliva with or without
      calcium ions and pH ranging from 4.5 to 7.5. Fluoride release from the studied
      materials was measured with an ion-selective electrode (Orion). The results
      demonstrate differing effects of calcium concentration and pH on fluoride
      release. The highest cumulative fluoride release was observed from Freedom and
      the lowest from Te-Econom. Addition of calcium ions to the medium reduced the
      release of fluoride.

PMID- 16892589
TI  - [Effect of accumulating fluorine and sulphur compounds on the content of
      chlorophyll in pine needles (Pinus sylvestris L.) from some areas of southern
      Poland in 2001-2003].
AB  - Concentrations of F(-), S and chlorophyll in needles of pines growing near
      metallurgical works and power plants were determined. A statistically significant
      positive correlation between F(-) (in the range of 4.32 to 21.98 microg F(-)/g
      d.m.) and chlorophyll and a negative correlation between S (in the range of 1094
      to 2150 microg S/g d.m.) and chlorophyll was found. This result suggests an
      antagonistic interaction between F(-) and S in pine needles.

PMID- 16892590
TI  - [Concentrations of fluorine, aluminum and magnesium in some structures of the
      central nervous system of rats exposed to aluminum and fluorine in drinking
      water].
AB  - Fluorine and aluminum are able to pass through the blood-brain barrier and
      accumulate in the central nervous system (CNS) of exposed animals. Chronic
      intoxication is accompanied by behavioral disorders, degenerative changes, and
      abnormalities of aerobic metabolism of the neurons. Awareness of the role of
      aluminum in Alzheimer's disease stems from epidemiological studies demonstrating
      increased prevalence of this condition in areas with relatively high content of
      aluminum in drinking water. The uptake of aluminum in the gastrointestinal tract
      is decreased in the presence of iron, calcium, magnesium, phosphate, or fluoride.
      Many magnesium-containing enzymes are affected by aluminum, which is able to
      replace magnesium and thus reduce their activity. The purpose of this study was
      to determine the concentrations of fluorine, aluminum, and magnesium in some
      structures of the CNS of rats exposed to fluorine and aluminum in water. Our
      material consisted of 64 Wistar rats divided into eight equal groups. Groups I,
      II and III were female rats exposed, respectively, to 100 ppm fluorine ions, 300
      ppm aluminum ions or both at same doses alternating every second day. Groups IA,
      IIA and IIIA consisted of male rats exposed like the respective female groups.
      Control groups K1--females and K2--males received distilled water ad libitum.
      Exposure lasted 31 days whereupon the animals were anesthetized with ketamine and
      sacrificed. The brain was collected and the cerebellum, brain cortex, and
      hippocampus were isolated. Concentrations of fluorine, aluminum, and magnesium
      were measured with prior mineralization of wet tissues in a microwave oven.
      Fluorine concentrations were determined with a potentiometric method and ion
      selective electrode. Aluminum was measured with ICP (inductively coupled plasma)
      and magnesium with ASA (atomic absorption spectrometry). The highest
      concentrations of fluorine were observed in rats exposed to fluorine only. The
      same pattern was true for aluminum. Groups exposed alternatively to both elements
      demonstrated lower accumulation of fluorine whereas accumulation of aluminum did
      not change significantly. Apparently, aluminum reduced the availability of
      fluorine but there was no reciprocal effect. No significant changes in the
      concentrations of magnesium were noted, regardless of the brain structure or
      group. It can thus be concluded that exposure to fluorine, aluminum or both has
      little effect on the concentration of magnesium in the CNS of rats.

PMID- 16892591
TI  - [The effect of fluorine substituent on radiochemical stability of some steroid
      and azole derivatives].
AB  - Radiochemical stability of three fluorine containing therapeutic substances:
      dexamethasone, fludrocortisone acetate (steroid derivatives) and fluconazole
      (azole derivative) has been studied. The compounds in the solid phase were
      exposed to ionising radiation in the form of electron beam using doses of 20-400
      kGy. The inital and irradiated compounds were subjected to comparative analyses
      by organoleptic, spectrophotometric (UV and IR) and chromatographic (TLC and
      HPLC) methods. For all compounds studied the irradiation was found to lead to a
      decrease in the active substance content (HPLC), appearance of radiolysis
      products (TLC), changes in the physical and chemical properties such as colour
      (fluconazole), formation of agglomerates (dexamethasone), decrease
      (dexamethasone, fludrocortisone acetate) or increase in UV absorption
      (fluconazole). The two steroid derivatives were found resistant to ionising
      radiation at doses of 25-50 kGy and can be sterilised by radiation, whereas
      fluconazole was too sensitive to electron beam irradiation and should be
      sterilised by other methods. The results were compared with those of earlier
      studies on radiation sterilisation of other steroid derivatives. An interesting
      conclusion is that the presence of the fluorine atom in the molecule of
      fludrocortisone acetate has no significant effect on its radiochemical stability
      when compared with that of hydrocortisone acetate--the analogue without fluorine.

PMID- 16892592
TI  - [Content of fluoride, calcium and magnesium in superficial layer of enamel from
      teeth with vital and necrotic pulp].
AB  - This work was designed to determine the content of fluorides, calcium, and
      magnesium in the superficial layer of enamel of adult teeth. The study group
      consisted of 25 patients, aged 18 to 35 years, appearing for dental treatment.
      Two microsamples of the superficial layer of enamel were collected from each
      patient with the acid biopsy technique. Samples were obtained from pulpectomized
      teeth treated endodontically and from teeth with necrotic pulp qualifying for
      endodontic treatment. Control samples were obtained from homonymous, caries-free
      teeth with vital pulp. The results of biochemical tests in the study group were
      compared with control teeth.

PMID- 16892593
TI  - [Effect of sodium fluoride in the presence of vitamin C on isolated rat
      hepatocytes].
AB  - Physiologically, prooxidants coexist in a dynamic equilibrium with factors that
      have antioxidant properties and so form an integrated antioxidant defence system
      of the organism. By determining the total antioxidant status (TAS) in the
      biological material it is possible to evaluate the influence of various factors
      on the organism's antioxidant properties. The aim of this study was to assess the
      influence of sodium fluoride and ascorbic acid on TAS. The results suggest that
      fluoride decreases TAS probably by stimulating free radical reactions.

PMID- 16892594
TI  - [Sample preparation methods for biomonitoring measurements of fluoride and metal
      content in tissues of mollusks].
AB  - Due to the toxicity of fluoride and some metals, their presence in the
      environment should be monitored regularly and with a simple method. The aim of
      this work was to analyze several methods for the preparation of tissues from
      mollusks prior to biomonitoring measurements of fluoride and metals. Preparation
      of samples for analysis requires the greatest effort and application of different
      procedures depending on the sample type. We present sample preparation procedures
      for the analysis of fluoride content in mollusk shell using the ion-selective
      electrode and in soft tissues using gas chromatography, as well as of metals in
      various mollusk tissues with atomic absorption spectrometry.

PMID- 16892595
TI  - [Fluorine and calcium in bones of the woodpigeon (Columba palumbus)].
AB  - A total of 90 woodpigeons shot in August and September 2002 in an area west of
      Szczecin were obtained from hunters. Based on their age and sex, the birds were
      divided into the following 4 groups: young males, young females, adult males, and
      adult females. Content of dry matter, ash, calcium, and fluorine were determined
      in the tarsometatarsus of each bird. No inter-group differences in per cent dry
      weight and ash contents were found. There was no correlation between fluorine and
      calcium contents with either dry weight or ash of the bones. However, significant
      differences in fluorine and calcium contents of bone ash were revealed between
      young and adult birds, regardless of sex, the two elements being more abundant in
      adult birds. Moreover, adult females differed from adult males, demonstrating
      higher fluorine content per bone dry weight. Adult birds regardless of sex showed
      higher fluorine content than young birds. A significant fluorine vs. calcium
      correlation was found in adult birds only. Correlation between per cent calcium
      and ash contents in bone dry weight was highly significant (r = 0.95; p <
      0.0001). The present study corroborates observations of other authors regarding
      age-related increase in the fluorine content in birds and a general lack of a
      clearcut relationship between the bone fluorine content and sex outside of
      breeding season. As shown by this study and the available literature, bones of
      herbivorous birds, including pigeons and geese are more representative for
      assessment of environmental fluorine pollution than bones of birds feeding on a
      mixed diet, carnivores, and scavengers. In view of the large variability in
      birds, comparisons should be made by studying analogous bones.

PMID- 16892596
TI  - [Content of fluoride in hair and hoofs of wild boars and deer from Western
      Pomerania as a bioindicator of environmental pollution].
AB  - The aim of this study was to assess the fluoride content in hair and hoofs of
      wild boars and deer from Western Pomerania (Poland). Fluoride content was
      determined with the Orion 96-09 fluoroselective electrode. The highest content of
      fluoride (13.39 microg/g d.m.) was found in hair of wild boars from the city of
      Stargard Szczecinski. The lowest fluoride content was in the control group of
      boars from the city of Pyrzyce (8.41 microg/g d.m.) and Mysliborz (6.11 microg/g
      d.m.). It was concluded that biomonitoring of fluoride accumulation in hair and
      hoofs may be useful for the assessment of environmental pollution with fluorine
      compounds.

PMID- 16892597
TI  - [Fifty Years of the "Journal of Parasitology" existence].

PMID- 16892598
TI  - [Cell structure and metabolism of the parasite Toxoplasma gondii--new aspects].
AB  - The article is based on newly published data concerning cell structure
      (cytoskeleton and cytoplasmic organelle) and biochemistry of the protozoon
      Toxoplasma gondii, many of which can be applied in therapy of toxoplasmosis.

PMID- 16892599
TI  - [Resistance in the hematophagous arthropods--problem on the rise. II: The
      consequences of resistance and management strategies to avoid resistance
      development].
AB  - Insecticide resistance has been a problem in all insects groups. Resistance has
      developed to every chemical class of insecticide, including microbial drugs and
      insect growth regulators. The result of rising resistance could be either
      increase in the number of arthropods cumbersome, like lice, or spread of
      arthropod-borne diseases, like malaria. The main tool of prevention against
      resistance is surveillance of the susceptibility of populations. Careful scrutiny
      of current information about vector resistance shows that the full effect of
      resistance on control efforts is not known. Resistance management strategies are
      dependent on early detection of the occurrence of resistance and efficient
      monitoring of resistance gene frequencies in populations. Detection of the
      susceptibility of a population could be shown trough bioassay, biochemical assay,
      or molecular assay. Resistance management can help avoid resistance development
      in populations or slow the rate of resistance development.

PMID- 16892601
TI  - Parasymphylodora parasquamosa Kulakova, 1972 (Trematoda, Digenea)--new species of
      the parasite fauna of Poland.
AB  - The present short note deals with atypical specimens of the digeneans, collected
      from fish Leuciscus idus caught in the Vistula mouth, and earlier described
      (Rokicki 1975) as Asymphylodora kubanicum (Issaitschikoff, 1923) Markewitsch,
      1951. The reexamination of these specimens indicated that they represent the
      species Parasymphylodora parasquamosa Kulakova, 1972. This is a new digenean
      species in the parasitic fauna of Poland.

PMID- 16892600
TI  - Nematodes of the intestine and swimbladder of the European eel Anguilla anguilla
      (L.) ascending Pomeranian rivers.
AB  - The study focused on the eel (length and weight averaging 23.1 cm and 13.7 g,
      respectively) ascending Pomeranian rivers in summers of 1999 - 2003. The swim
      bladder was examined in 322 individuals, the intestine being examined in 272
      fish. Anguillicola crassus was present in the swim bladder of 184 fish. Infection
      prevalence varied between the rivers, the highest prevalence being recorded in
      the eel caught in the Radew (65.6%) and the lowest in the Wieprza (41.7%). The
      intensity of infection was generally low, the mean values varying from 2.1 in the
      Rega to 1.3 in the Wieprza. The coefficient of infection was low (0.11 to 0.12).
      Spinitectus inermis was present, with low intensity, in the intestine of 18 fish
      (6.6%). The nematode had not been recorded in the eel in Poland for 70 years. In
      addition, the intestine of the eel under study was found to house Raphidascaris
      acus and Paraquimperia tennerima, each present as a single larva. This is the
      first record of the latter in Poland. The infection of eel from the Radew river
      that stayed in the fresh water for a longer time was higher than that of the eel
      found in the Rega and Wieprza.

PMID- 16892602
TI  - [Seasonal dynamics of Ceratophyllus hirundinis (Curtis, 1826) (Siphonaptera,
      Insecta) in the nests of Delichon urbica (L.)].
AB  - The annual cycle of C. hirundinis was studied in 61 nests of Delichon urbica.
      Fleas were found in the 45 nests. In the number of adults two peaks were
      observed, the lower in March and the higher in October. Females outnumbered males
      throughout the year.

PMID- 16892604
TI  - [Some aspects of the skin infestation by Demodex folliculorum].
AB  - The importance of demodicids (Demodex folliculorum and D. brevis) infestation and
      their effect on skin lesions has been described based on literature data and our
      own clinical and parasitological investigations. Hair follicle mites have been
      detected in 45% of patients with rosacea, 27% of patients with perioral
      dermatitis, 28% of patients suffering from seborrhoeic dermatitis and in 3 out of
      7 patients with chronic blepharitis. Clinical picture of demodecosis included
      erythemato-papulous and pustulous (rosacea-like) skin lesions together with
      erythemato-desquamative changes of the face.

PMID- 16892603
TI  - [Familial infections with Trichomonas tenax (O.F. Muller, 1773), Dobel, 1939].
AB  - Aim of the study was to research familial occurrence of Trichomonas tenax and
      relationship between infection with the protozoan and both a state of parodontium
      and hygiene of oral cavity. The study involved 10 families (22 individuals).
      Trichomonas tenax was found in 16 patients. Simultaneously isolates of protozoans
      were examined with the methods of molecular biology. The study showed the
      dependence of infection with Trichomonas tenax on both bad hygiene of oral cavity
      and occurrence of pathological lesions in the paradontium.

PMID- 16892605
TI  - [Symptomatic and asymptomatic infections of Demodex spp. in eye lashes of
      patients of different age groups].
AB  - Demodex folliculorum and Demodex brevis were looked for on eyelashes sampled from
      481 people, aged 3 through 96. The persons studied were divided into 9 age
      groups. Magnitude of the infection symptoms was assessed based on macroscopic
      changes of eye-lid edges and on interviews with patients. An increase of the
      prevalence of infection and intensification of the symptoms were observed to
      coincide with the age increase of the persons studied. No significant differences
      were demonstrated between the infection frequencies of women and men. Symptoms of
      ocular demodecosis were more frequent only in women of group III (aged 21-30) and
      group V (41-50) (p < 0.05).

PMID- 16892606
TI  - [II workshops on bird schistosomes].

PMID- 16892607
TI  - [Prof. Zbigniew Juliusz Jara--a parasitologist and the editor of Wiadomosci
      Parazytologiczne].

PMID- 16892608
TI  - [Professor Zbigniew Kabata, Honorary Member of the Polish Parasitological Society
      the 80th anniversary].

PMID- 16892609
TI  - [Accurate assessment of heart murmurs in children: thorough medical history and
      physical examination required].
AB  - 4 children, boys aged 12, 5, 1.5 and 11 years, had a heart murmur. The 12-year
      old boy could also not finish a football match and appeared to have atrioseptal
      defects (ASD). The 1.5-year-old boy had pulmonary symptoms that were not
      responsive to asthma medication; he also had ASD. The 11-year-old boy had had
      chest pain and pressure following exertion for 2 years; he appeared to have an
      aortic stenosis. Symptoms disappeared in all 3 patients after surgical
      correction. In the 5-year-old asymptomatic boy the murmur was deemed to be
      innocent following medical history and physical examination. Children frequently
      have heart murmurs. Most heart murmurs are innocent but some are caused by heart
      defects. Careful evaluation of the medical history and physical examination are
      critical in the differentiation of innocent and pathological heart murmurs.
      Routine supplementary diagnostic tests in children with heart murmurs are of
      limited value and are often misleading. One should inquire about specific and
      nonspecific symptoms and also perform systematic inspection, palpation and
      auscultation to identify any characteristics that suggest a heart murmur caused
      by a heart defect.

PMID- 16892610
TI  - [Stem cells: hype and hope].
AB  - There is increasing interest in the use of stem cells for therapeutic purposes.
      The use of embryonic stem cells carries ethical and legal restrictions that limit
      their role in tissue regeneration. These restrictions do not apply to somatic
      stem cells, such as haematopoietic stem cells, which normally reside in the bone
      marrow. Preclinical studies have produced very promising results using these
      cells in experimental models of myocardial infarction. Bone-marrow cells have
      also been used to generate several different types of tissue. However,
      experimental data suggest that bone marrow also houses other non-haematopoietic
      stem cells, which could account for the alleged plasticity of haematopoietic stem
      cells. So far, the results of randomised clinical trials in patients with
      myocardial infarction or heart failure have been disappointing. It is clear that
      further research in this field is needed.

PMID- 16892611
TI  - [Emergency procedures for taking care of the victims of bomb attacks: logistical
      and medical aspects].
AB  - In The Netherlands the threat of terrorist attacks also exist. Both doctors and
      hospitals alike should be prepared for such attacks both on the logistical as
      well as the medical level. Most terrorist attacks are carried out with
      explosives. This results in many victims and in cases of explosions in closed or
      semi-closed areas, often results in complex medical problems in many of the
      victims. An explosion that occurs as the result ofa bomb detonating can result in
      4 patterns of injury: the primary explosion injury caused by the pressure of the
      blast, the secondary injuries caused by flying debris, the tertiary injuries
      caused by the explosion wind, and the quaternary caused by heat and fire. Common
      injuries seen following an explosion include: lung damage, neurological damage,
      abdominal injuries, bone fractures and skeletal damage and crush-syndrome. The
      triage occurs at the site of the explosion as well as on arrival in hospital. One
      especially important aspect of this is the sorting and selecting between victims
      who are likely to develop complex problems and who therefore need to receive
      aggressive treatment in a specially equipped centre and those patients for whom
      the nearest emergency department will suffice their needs. The triage should be
      repeated considering the possibility that initial estimates on these points may
      have been wrong. Epidemiological research should be carried out for each attack
      in order to make an inventory of the number of victims, the injuries incurred,
      the assessment of the effects of the medical help received and an assessment of
      the effectiveness of the total aid received.

PMID- 16892612
TI  - [Damage control surgery in polytraumatized patients].
AB  - Care for the polytraumatized patient in the pre-hospital phase has improved
      rapidly in recent years. This has resulted in more patients being alive on
      arrival at the hospital. The treatment of polytraumatized patients requires a
      different approach to that of regular trauma patients because they are threatened
      not only by the injuries themselves but also by the metabolic disruptions that
      follow. Therefore, the concept of damage control surgery (DCS) has been developed
      with the primary aim of controlling the life-threatening situation without
      immediate definitive repair of the sustained injuries. DCS describes a triphasic
      approach for abdominal and thoracic injuries and for injuries of the pelvic and
      extremities. The first phase aims at surgical intervention to stop the bleeding
      and to prevent further contamination. The second phase consists of resuscitation
      on the Intensive Care Unit and the third phase aims at definitive repair of the
      sustained injuries. Despite the low level of evidence found in the literature,
      DCS seems to reduce mortality rates in polytraumatized patients. Therefore, when
      initiated correctly and at the right moment, it appears to be a promising
      technique.

PMID- 16892613
TI  - [Diagnostic image (281). A girl with fever, a sore throat and a rash].
AB  - Scarlet fever was diagnosed in a girl with high fever, a sore throat and
      exanthema marginatum.

PMID- 16892614
TI  - [Physicians and scientific research: slight decline of the numbers of physicians
      with a doctoral degree].
AB  - OBJECTIVE: To establish whether the number of physicians interested in a career
      in academia (i.e. research) is declining. DESIGN: Descriptive. METHOD: The
      researchers analysed the pre- and post-doctoral careers of PhD students at 3
      university medical centres (VU Amsterdam, Nijmegen and Maastricht) in 4 separate
      reference years (1989, 1994, 1999 and 2003), using information from doctoral
      dissertations and the Dutch medical address book. The researchers recorded the
      gender of the students and the timing of the doctorate in relation to specialist
      training, university education and employment, as applicable. RESULTS: The total
      number of dissertations produced at the 3 medical faculties in the 4 reference
      years increased gradually by nearly a factor of 2 (1989: 112; 1994: 152; 1999:
      198; 2003: 213). In terms of absolute numbers, the number of dissertations
      authored by physicians increased from 1989 to 1994 and again in 1999 (64, 90 and
      105), but decreased slightly in 2003 (96). The percentage of female physicians
      obtaining a doctorate doubled during this period (1989: 9/64 (14); 2003: 28/96
      (29)). Increasingly, physicians prepared their dissertation before or during
      their training as specialists or general practitioners (1989: 15/64 (23%); 2003:
      51/96 (53%)). Ofthe clinical specialists who had received their doctorate,
      approximately half continued to work in an academic setting after obtaining their
      degree. This percentage remained approximately the same in all reference years
      (1989: 13/26 (50); 1994:19/35 (54); 1999: 21/45 (47); 2003: 21/40 (53)).
      CONCLUSION: Although the number of physicians performing scientific research as
      part of their doctoral degree project declined slightly in 2003 following an
      initial rise, our data indicate no cause for major concern. One reason may be
      increased interest in Clinical Research Fellow programmes. However, the future of
      medical research would look brighter if young physicians with doctorates had
      better career prospects within academic centres. To follow the academic careers
      of clinicians in The Netherlands, a national registry is needed to collect the
      type of data analysed in this study continually.

PMID- 16892615
TI  - [Favourable results with local injections of botulinum-A toxin in patients with
      chronic isosorbide dinitrate ointment-resistant anal fissures].
AB  - OBJECTIVE: To determine the effectiveness of injection of botulinum-A toxin in
      the internal anal sphincter as a treatment for chronic therapy-resistant anal
      fissures. DESIGN: Prospective. METHODS: In the period October 2002-February 2005,
      32 consecutive patients (15 men and 17 women), with a median age of 44 years
      (range: 23-78 years) and suffering from chronic isosorbide dinitrate ointment
      resistant anal fissures, were treated with an injection of 40 IU botulinum-A
      toxin (Dysport, Ipsen, The Netherlands) in the ventral side of the internal anal
      sphincter. The injection was given as an outpatient procedure under general or
      spinal anaesthesia. RESULTS: After a median follow-up of 14 months (range: 2-28
      months), the chronic anal fissures were cured in 24 ofthe 32 patients (75%).
      Twenty-two patients were given a second or a third injection. A fissure recurred
      in one of the cured patients (4%), and one patient suffered from temporary flatus
      incontinence. CONCLUSION: Botulinum-A toxin injections were effective in 75% of
      patients with isosorbide dinitrate ointment-resistant chronic anal fissures. This
      is a simple technique with fewer side effects than local application of NO donors
      and fewer complications and less morbidity than surgical sphincterotomy.

PMID- 16892616
TI  - [A 26-year-old cyclist with intermittent claudication].
AB  - A 26-year-old male amateur cyclist, with no risk factors for vascular disease or
      previous trauma, presented with left-calf claudication. Physical and additional
      examination revealed an occlusion of the external iliac artery. During the
      operation, the cause was found to be an endofibrotic lesion of the external iliac
      artery, probably due to mechanical trauma as a result of the non-physiological
      aerodynamic position held on the bicycle during many hours of training. An
      endarterectomy was performed and the tendon of the psoas-minor muscle was cut
      because of its strong impression on the psoas-major muscle, which resulted in
      kinking of the external iliac artery. There followed two episodes of re-occlusion
      which were treated with a venous interposition graft and a dacron interposition
      graft, respectively. Thereafter the patient was able to train without pain.
      Intermittent claudication of the legs in young athletes should not be
      underestimated; occlusive vascular disease caused by arterial endofibrosis should
      be considered.

PMID- 16892617
TI  - [Intramyocardial injection of autologous bone-marrow stem cells in a 74-year-old
      man with untreatable angina pectoris and demonstrated myocardial ischaemia].
AB  - For a 74-year-old man with angina pectoris and demonstrated myocardial ischaemia,
      optimal medical treatment was insufficient. He was ineligible for coronary
      revascularization. To improve myocardial perfusion, autologous bone-marrow stem
      cells were injected into the ischaemic myocardium. During the months following
      the injection, the frequency of angina attacks decreased and myocardial perfusion
      and cardiac function improved.

PMID- 16892618
TI  - [Outcomes of disciplinary proceedings against gynaecologists: comparison between
      the periods 1980-1991 and 1992-2003].
AB  - In a study of the archives of the Chief Inspector for Healthcare in The
      Netherlands during the period 1992-2003, the number of complaints against
      gynaecologists submitted to disciplinary boards (n = 371) was found to be higher
      than during the period of 1980-1991 (n = 240). On the other hand, the number of
      complaints per gynaecologist had decreased from 6.3 complaints per 100
      gynaecologists in 1992 to 2.6/100 in 2003. The number ofcomplaints declared
      legitimate relative to the number of submitted complaints remained the same in
      both periods (55/240 (23%) in 1980-1991 and 84/371 (23%) in 1992-2003), although
      the percentage ofcomplaints ruled as legitimate did increase during the course of
      the second period from 14 between 1992-1997 to 28 during the 1998-2003 period.
      Interesting points included the number of rulings regarding the death of an
      infant (40%), the interpretation of the cardiotocography recording, the need to
      keep medical records up to date (in particular the informed consent) and the fact
      that almost 50% of complaints ruled to be legitimate related to how the locum
      position was arranged, the role of the duty gynaecologist and that of the house
      officer.

PMID- 16892619
TI  - [The danger to health from fine dust particles in the air].

PMID- 16892620
TI  - [The use of complementary and alternative medicine in children at a general
      paediatric clinic and parental reasons for use].

PMID- 16892621
TI  - Impact of phlebotomine sand flies on U.S. Military operations at Tallil Air Base,
      Iraq: 1. background, military situation, and development of a "Leishmaniasis
      Control Program".
AB  - One of the most significant modern day efforts to prevent and control an
      arthropod-borne disease during a military deployment occurred when a team of U.S.
      military entomologists led efforts to characterize, prevent, and control
      leishmaniasis at Tallil Air Base (TAB), Iraq, during Operation Iraqi Freedom.
      Soon after arriving at TAB on 22 March 2003, military entomologists determined
      that 1) high numbers of sand flies were present at TAB, 2) individual soldiers
      were receiving many sand fly bites in a single night, and 3) Leishmania parasites
      were present in 1.5% of the female sand flies as determined using a real-time
      (fluorogenic) Leishmania-generic polymerase chain reaction assay. The rapid
      determination that leishmaniasis was a specific threat in this area allowed for
      the establishment of a comprehensive Leishmaniasis Control Program (LCP) over 5
      mo before the first case of leishmaniasis was confirmed in a U.S. soldier
      deployed to Iraq. The LCP had four components: 1) risk assessment, 2) enhancement
      of use of personal protective measures by all personnel at TAB, 3) vector and
      reservoir control, and 4) education of military personnel about sand flies and
      leishmaniasis. The establishment of the LCP at TAB before the onset of any human
      disease conclusively demonstrated that entomologists can play a critical role
      during military deployments.

PMID- 16892622
TI  - Developing an evidence-based decision support system for rational insecticide
      choice in the control of African malaria vectors.
AB  - The emergence of Anopheles species resistant to insecticides widely used in
      vector control has the potential to impact directly on the control of malaria.
      This may have a particularly dramatic effect in Africa, where pyrethroids
      impregnated onto bed-nets are the dominant insecticides used for vector control.
      Because the same insecticides are used for crop pests, the extensive use and
      misuse of insecticides for agriculture has contributed to the resistance problem
      in some vectors. The potential for resistance to develop in African vectors has
      been apparent since the 1950s, but the scale of the problem has been poorly
      documented. A geographical information system-based decision support system for
      malaria control has recently been established in Africa and used operationally in
      Mozambique. The system incorporates climate data and disease transmission rates,
      but to date it has not incorporated spatial or temporal data on vector abundance
      or insecticide resistance. As a first step in incorporating this information,
      available published data on insecticide resistance in Africa has now been
      collated and incorporated into this decision support system. Data also are
      incorporated onto the openly available Mapping Malaria Risk in Africa (MARA) Web
      site (http://www.mara.org.za). New data, from a range of vector population
      monitoring initiatives, can now be incorporated into this open access database to
      allow a spatial understanding of resistance distribution and its potential impact
      on disease transmission to benefit vector control programs.

PMID- 16892623
TI  - Importance of algal biomass to growth and development of Anopheles gambiae
      larvae.
AB  - We conducted experiments to investigate the importance of algal food resources
      for larval growth and adult emergence of Anopheles gambiae Giles s.s. in
      simulated larval habitats in Kenya, and in greenhouse and laboratory microcosms
      in the United States. In the first experiment, we used shading to reduce algal
      biomass, and because algal production and larval development might be a function
      of underlying soil nutrients, we crossed sun-shade treatments with soils of two
      distinct types collected near larval habitats. Shading reduced pupation rates and
      total adult biomass of An. gambiae by approximately 50%. Soil type had no
      significant effect on mosquito production, but it did significantly affect
      concentrations of phosphorus and chlorophyll a in the surface microlayer. In a
      subsequent experiment conducted in the greenhouse to reduce temperature
      differences found between the shaded and sunlit treatments, <1% of larvae in the
      shaded treatments reached the pupal stage. There was a marked reduction of
      chlorophyll a levels as a function of shading and larval density. In a third
      experiment, larvae receiving material harvested from sunlit surface microlayers
      performed as well as those receiving liver powder, whereas those receiving
      surface microlayer from shaded habitats suffered >90% mortality and failed to
      pupate. In a fourth experiment, glucose was added to shaded microcosms to
      stimulate bacterial activity in the absence of algae. Bacterial growth rates were
      2 to 3 times higher, and larval development was enhanced in glucose-amended
      treatments. However, pupation rates and adult weights in glucose-amended shaded
      microcosms were still poor compared with those in nonamended sunlit microcosms.
      Overall, these results demonstrate the importance of algal biomass in the surface
      microlayers of larval habitats to development and adult production of An.
      gambiae.

PMID- 16892624
TI  - Indirect effects of soluble nitrogen on growth of Ochlerotatus triseriatus larvae
      in container habitats.
AB  - We conducted experiments in laboratory microcosms to simulate input of stemflow
      nutrients and flushing of metabolites in the tree hole habitats of larval
      Ochlerotatus triseriatus (Say). In the first experiment, we simultaneously
      examined the effects of nutrient additions (nitrogen, phosphorus, glucose, or
      combination) and flushing (removal of one-half of water volume replaced by
      deionized water) on mosquito production. The combination of nutrients had the
      greatest positive effects on mosquito production, with nitrogen (N) likely
      accounting for most of the increase in adult emergence and adult mass. Dilution
      of the nutrient pool via simulated flushing reduced mosquito growth, suggesting
      that the primary effect of stemflow input was nutrient addition as opposed to
      dilution of any latent toxic metabolites. In a second experiment, N additions
      were crossed with larval presence or absence to examine effects on key microbial
      processes. N increased leaf decay rates, soluble carbohydrate concentrations,
      fungal biomass and leaf-associated carbohydrase activity, but it did not
      stimulate bacterial productivity. Leaf decay was enhanced and bacterial
      production on leaves and in the water column was depressed in the presence of
      larvae. We conclude that the inputs of soluble N stimulated fungal growth, which
      made more fungal biomass available because of both its absolute increase and via
      the softening of the leaf particulate matter that could allow direct ingestion by
      larvae.

PMID- 16892625
TI  - Wolbachia effects on Aedes albopictus (Diptera: Culicidae) immature survivorship
      and development.
AB  - Wolbachia bacteria manipulate the reproduction of mosquito hosts via a form of
      sterility known as cytoplasmic incompatibility (CI), promoting the spread of
      infections into host populations. The rate at which an infection invades is
      affected by host fitness costs associated with the Wolbachia infection. Here, we
      examine for an effect of Wolbachia infection on the immature fitness of the Asian
      tiger mosquito Aedes albopictus (Skuse) (Diptera: Culicidae). In two experiments,
      we examine for a Wolbachia effect on immature survivorship and developmental
      rate, adult size, and an effect of larval nutrition on CI level. The highest
      survivorship can be observed in uninfected larvae, primarily because of reduced
      survivorship of Wolbachia-infected males. Although differences in the
      developmental rates are observed between the examined strains, the differences
      cannot be readily attributed to Wolbachia. An effect of Wolbachia on adult size
      is not observed. Poor male nutrition is associated with reduced fecundity and egg
      hatch of mates. The latter is hypothesized to explain the reduced egg hatch
      observed in CI crosses of malnourished males relative to well fed males. We
      discuss the results in relation to previously identified differences in adult
      fitness, naturally occurring invasions of Wolbachia, applied strategies of
      population replacement, and the need for additional modeling effort.

PMID- 16892626
TI  - Geographic distribution of Wolbachia infections in Cimex lectularius
      (Heteroptera: Cimicidae).
AB  - Endosymbiotic Wolbachia bacteria have been previously shown to infect laboratory
      colonies of the human bed bug, Cimex lectularius L. (Heteroptera: Cimicidae), but
      little information exists regarding the extent of infection in natural
      populations. We assayed C. lectularius populations from five North American
      regions (California, Connecticut, Florida, New York, and Toronto, Canada) and one
      African region (Macha, Zambia) for Wolbachia infection by the polymerase chain
      reaction (PCR). Wolbachia infections were prevalent in all populations assayed
      (83-100%). There were no significant differences in infection frequency between
      geographic regions, between sexes, or between life stages (adult versus nymph).
      The potential utility of Wolbachia for alternative bed bug control strategies is
      discussed.

PMID- 16892627
TI  - Analysis of genetic variation in ribosomal DNA internal transcribed spacer and
      the NADH dehydrogenase subunit 4 mitochondrial genes of the onchocerciasis vector
      Simulium ochraceum.
AB  - Onchocerciasis is a serious disease vectored by black flies in the genus Simulium
      that are infected with the filarial parasite Onchocerca volvulus. In the
      Americas, black flies of the Simulium ochraceum s.l. species complex are
      important vectors of this parasite. Cytological studies have suggested that this
      species complex consists of at least three cytotypes that inhabit distinct
      habitats. In this study, the NADH dehydrogenase subunit four (ND4) and internal
      transcribed spacer (ITS) of the ribosomal RNA gene cluster were used to explore
      the degree of genetic diversity among S. ochraceum s.l. populations found in the
      three O. volvulus foci in Mexico. Both sequence regions were found to exhibit
      intra- and interpopulation variation. Four different ND4 alleles were found among
      the populations examined. Similarly, variation was noted in the ITS domain
      sequences within and among populations. Variation within the ITS sequence was
      primarily confined to a complex microsatellite locus. Four ITS length variants
      were observed, two of which were only seen in flies collected from the
      onchocerciasis focus in northern Chiapas. These data suggest that the ND4 and ITS
      sequences may prove to be useful markers for exploring interactions within and
      among the S. ochraceum s.l. populations in Mexico.

PMID- 16892628
TI  - Baculovirus expression of BmAChE3, a cDNA encoding an acetylcholinesterase of
      Boophilus microplus (Acari: Ixodidae).
AB  - The complete cDNA sequence encoding a Boophilus microplus (Canestrini) (Acari:
      Ixodidae) acetylcholinesterase (AChE3) was expressed in the baculovirus system.
      The recombinant AChE3 protein (rBmAChE3) was secreted as a soluble form into the
      cell culture medium and was identified as a functional AChE by substrate
      specificity and by inhibition with the AChE-specific inhibitors eserine sulfate
      and BW284c51. Inhibition kinetics of rBmAChE3, in the presence of the
      organophosphate paraoxon, revealed sensitivity comparable with that of adult,
      organophosphate-susceptible neural AChE. To our knowledge, this is the first
      report of the cloning and successful expression of a functional ixodid AChE.

PMID- 16892629
TI  - Enhanced cold and desiccation tolerance in diapausing adults of Culex pipiens,
      and a role for Hsp70 in response to cold shock but not as a component of the
      diapause program.
AB  - Culex pipiens L. reared under diapause-inducing conditions (short daylength; 18
      degrees C) were more cold tolerant and desiccation resistant than their
      nondiapausing counterparts (long daylength; 18 degrees C). Upon cold exposure (-5
      degrees C), diapausing mosquitoes reared at 18 degrees C survived nearly twice as
      long as nondiapausing mosquitoes reared at 18 degrees C and 10 times longer than
      nondiapausing mosquitoes reared at 25 degrees C. Thus, rearing temperature
      provided partial protection against low temperature injury in nondiapausing
      mosquitoes, but maximum resistance to cold was attained by the diapause state. In
      this species, the supercooling point is not a good indicator of cold tolerance.
      Both diapausing and nondiapausing females had supercooling points of
      approximately -16 degrees C, but diapausing as well as nondiapausing females died
      at temperatures well above the supercooling point, suggesting that low
      temperature mortality was due to indirect chilling injury. Diapause also
      conferred greater resistance to desiccation (1.6-2-fold increase in survival)
      compared with the nondiapause state. The gene encoding a 70-kDa heat shock
      protein, hsp70, was not up-regulated (i.e., more highly expressed) as a part of
      the diapause program, nor was it up-regulated by desiccation stress, but it was
      up-regulated during recovery from cold shock. Cx. pipiens thus differs from a
      number of other diapausing insect species that are known to developmentally up
      regulate hsp70 during diapause.

PMID- 16892630
TI  - Use of temperature and water immersion to control the human body louse (Anoplura:
      Pediculidae).
AB  - Physical methods such as high and low temperatures were used in the past for the
      control of human body louse, Pediculus humanus humanus L. (Anoplura:
      Pediculidae). In the current study, the minimum time necessary to kill all lice
      after exposing them to temperatures other than those described in the literature,
      the mortality of lice after immersing them in water, and the survival of lice
      whose legs were amputated were studied. All lice died after 6 d at 6 degrees C,
      after 11 d at 24 degrees C, and after 9 d at 31 degrees C. At -17 degrees C, all
      lice were dead after 35 min, whereas at -70 degrees C, all lice were dead after 1
      min. All lice died after immersion in water within 19 h. The differences in
      mortality were significant but borderline between controls and lice whose two
      legs were amputated immediately or 24 h after feeding (3.3 versus 13.3% and 8.3
      versus 21.7%). For lice whose leg was amputated 48 h after feeding, significant
      differences were found between controls and lice with one amputated leg (13.3
      versus 48.3%), between controls and lice with two amputated legs (13.3 versus
      68.3%), and between lice with one and two amputated legs (48.3 versus 68.3%).

PMID- 16892631
TI  - Mosquitocidal toxin from Bacillus sphaericus induces stronger delayed effects
      than binary toxin on Culex quinquefasciatus (Diptera: Culicidae).
AB  - We studied the toxicity and delayed effects of a mosquitocidal toxin (Mtx1) and a
      binary toxin (Bin) produced in Escherchia coli E-TH21 and Bacillus thuringiensis
      B-CW1, respectively, on Culex quinquefasciatus (Diptera: Culicidae). Bioassay
      results showed that both E-TH21 powder and B-CW1 sporulated culture were highly
      toxic against susceptible Cx. quinquefasciatus, with LC50 values of 0.65 and 1.70
      mg/liter against third and fourth instars at 48 h, respectively. After initial 48
      h exposure of larvae to different concentrations of Mtx1 and Bin, significant
      continued mortality could be observed in larval, pupal, and emergence stages of
      Cx. quinquefasciatus. Importantly, the Mtx1 could induce higher cumulative larval
      and preadult mortalities than Bin toxin on the target mosquito. This finding is
      important for understanding the mode of action of Mtx1 and Bin toxins and for
      developing a new bioassay procedure for evaluation of toxicity of Bacillus
      sphaericus Neide, some strains of which produce Mtx1 and Bin, in the laboratory
      and field.

PMID- 16892632
TI  - Repellency of oils of lemon eucalyptus, geranium, and lavender and the mosquito
      repellent MyggA natural to Ixodes ricinus (Acari: Ixodidae) in the laboratory and
      field.
AB  - MyggA Natural (Bioglan, Lund, Sweden) is a commercially available repellent
      against blood-feeding arthropods. It contains 30% of lemon-scented eucalyptus,
      Corymbia citriodora (Hook.) K. D. Hill & L. A. S. Johnson (Myrtaceae), oil with a
      minimum of 50% p-menthane-3,8-diol. MyggA Natural also contains small amounts of
      the essential oils of lavender, Lavandula angustifolia Mill. (Lamiaceae), and
      geranium, Pelargonium graveolens L'Her. (Geraniaceae). In laboratory bioassays,
      MyggA Natural and C. citriodora oil exhibited 100% repellency against host
      seeking nymphs of Ixodes ricinus (L.) (Acari: Ixodidae). Lavender oil and
      geranium oil, when diluted to 1% in 1,2-propanediol, had weak repellent
      activities on I. ricinus nymphs, but when diluted to 30% in 1,2-propanediol had
      100% repellencies. 1,2-Propanediol (100%) had no significant repellent activity
      in comparison with that of the control. In field tests in tick-infested areas in
      central Sweden, tick repellency of MyggA Natural and C. citriodora oil was tested
      by the blanket-dragging technique for 4 d during a 6-d period. The repellencies
      (74 and 85%, respectively) on day 1 are similar (89%) to that of blankets treated
      in a similar manner with 19% diethyl-methyl-benzamide, based on previous work.
      Repellencies declined significantly from day 1 to day 6 (74 to 45% for MyggA
      Natural; 85 to 42% for C. citriodora oil).

PMID- 16892633
TI  - Reservoir role of lizard Psammodromus algirus in transmission cycle of Borrelia
      burgdorferi sensu lato (Spirochaetaceae) in Tunisia.
AB  - To investigate the reservoir role of the lizard Psammodromus algirus for the Lyme
      disease spirochete, 199 lizards were trapped from April to October 2003 in El
      Jouza, northwestern Tunisia. In this site, the infection rate of free-living
      Ixodes ricinus (L.) by Borrelia was evaluated by immunofluorescence as 34.6% for
      adult ticks and 12.5% for nymphs. Eighty percent of P. algirus (117/146) captured
      during this study were infested by I. ricinus, the predominant tick species
      collected from lizards. The intensity of tick infestation of this host by larvae
      and nymphs ranged from 0.14 to 7.07 and from 1.5 to 6.58, respectively. These
      immature stages of I. ricinus were found on lizards in spring and the beginning
      of summer, with a peak of intensity during June (10.16 immature ticks by lizard).
      Tissue cultures from lizards and xenodiagnosis with larval I. ricinus were used
      to assess the infection and the ability, respectively, of infected lizards to
      transmit Borrelia to naive ticks. Seventeen percent of xenodiagnostic ticks
      (40/229) acquired B. lusitaniae while feeding on P. algirus. Therefore, we
      demonstrated the ability of the lizards to sustain Borrelia infection and to
      infect attached ticks, and we proved that P. algirus is a reservoir host
      competent to transmit B. lusitaniae.

PMID- 16892634
TI  - Sylvatic maintenance of Borrelia burgdorferi (Spirochaetales) in Northern
      California: untangling the web of transmission.
AB  - Lyme borreliosis is associated with several genospecies of Borrelia burgdorferi
      sensu lato (s.l.) (Spirochaetales), but human disease has been associated only
      with Borrelia burgdorferi sensu stricto (s.s.) Johnson, Schmid, Hyde, Steigerwalt
      & Brenner in the western United States. Restriction fragment length polymorphism
      (RFLP) analysis of rrf-rrl amplicons from 124 tick and mammalian isolates from
      various habitats yielded 13 RFLP patterns. Of these patterns, six were patterns
      previously associated either with Borrelia bissettii Postic, Marti Ras, Lane,
      Hendson & Baranton or Borrelia burgdorferi s.s., and the remaining seven patterns
      belonged to diverse and previously uncharacterized Borrelia spp. Uncharacterized
      Borrelia spp. were cultured most frequently from Ixodes spinipalpis Hadwen &
      Nuttall and California kangaroo rats, Dipodomys californicus Merriam, inhabiting
      grasslands, and B. bissettii from I. spinipalpis and dusky-footed woodrats,
      Neotoma fuscipes Baird, associated with oak woodlands or chaparral. B.
      burgdorferi s.s. typically was isolated from host-seeking Ixodes pacificus Cooley
      & Kohls collected in dense oak woodlands, woodland-grass, or redwood forests.
      Although some isolates of B. burgdorferi s.s. were cultured from woodrats, there
      was no clear association of this human pathogen with any vertebrate host. These
      findings, along with recent evidence indicating that the western gray squirrel,
      Sciurus griseus Ord, may be an important reservoir of B. burgdorferi s.s. in
      Californian oak woodlands, suggest that our earlier hypothesis implicating an
      enzootic cycle involving woodrats and I. spinipalpis is insufficient to account
      for observed patterns of infection in nature.

PMID- 16892635
TI  - Parallel infection of Japanese encephalitis virus and Wolbachia within cells of
      mosquito salivary glands.
AB  - The endosymbiont Wolbachia usually causes cytoplasmic incompatibility in dipteran
      hosts, including mosquitoes. However, some important arbovirus-transmitting
      mosquitoes such as Aedes aegypti (L.) are not heritably infected by Wolbachia. In
      Wolbachia-harboring mosquito Armigeres subalbatus Coquillett, colocalization of
      Wolbachia and inoculated Japanese encephalitis virus (family Flaviviridae, genus
      Flavivirus, JEV) in salivary gland (SG) cells was shown by electron microscopy.
      The infection rate of JEV in SGs, detected with either immunofluorescent antibody
      test or reverse transcription-polymerase chain reaction, did not show significant
      differences between Wolbachia-infected and -free colonies. It is suggested that
      Wolbachia did not mediate resistance of SG cells to superinfection by JEV,
      although both microorgamisms coexist in the same niche, i.e., the same SG cell.
      Therefore, a SG escape barrier may not be elevated due to Wolbachia infection,
      which presumably has no deleterious effects on vector competence in Wolbachia
      harboring mosquitoes.

PMID- 16892636
TI  - Comparative potential of Aedes triseriatus, Aedes albopictus, and Aedes aegypti
      (Diptera: Culicidae) to transovarially transmit La Crosse virus.
AB  - Aedes triseriatus (Say) (Diptera: Culicidae), the major vector of La Crosse (LAC)
      virus, efficiently transmits LAC virus both horizontally and transovarially. We
      compared the vector competence and transovarial transmission ability of Ae.
      triseriatus, Aedes albopictus Skuse, and Aedes aegypti (L.) for LAC virus. Ae.
      triseriatus and Ae. albopictus were significantly more susceptible to oral
      infection with LAC virus than Ae. aegypti. The three species also differed in
      oral and disseminated infection rates (DIRs). Transovarial transmission (TOT)
      rates and filial infection rates (FIRs) were greater for Ae. triseriatus than
      either Ae. albopictus or Ae. aegypti. These measures were integrated into a
      single numerical score, the transmission amplification potential (TAP) for each
      species. Differences in TAP scores were due mainly to the differences in DIRs and
      FIRs among these mosquitoes. Although the TAP score for Ae. albopictus was lower
      than that of Ae. triseriatus, it was 10-fold greater than that for Ae. aegypti.

PMID- 16892637
TI  - Distribution and characterization of Borrelia burgdorferi isolates from Ixodes
      scapularis and presence in mammalian hosts in Ontario, Canada.
AB  - The blacklegged tick, Ixodes scapularis Say (Acari: Ixodidae), has a wide
      geographical distribution in Ontario, Canada, with a detected range extending at
      least as far north as the 50th parallel. Our data of 591 adult I. scapularis
      submissions collected from domestic animals (canines, felines, and equines) and
      humans during a 10-yr period (1993-2002) discloses a monthly questing activity in
      Ontario that peaks in May and October. The Lyme disease spirochete Borrelia
      burgdorferi Johnson, Schmidt, Hyde, Steigerwalt & Brenner was detected in 12.9%
      of I. scapularis adults collected from domestic hosts with no history of out-of
      province travel or exposure at a Lyme disease endemic area. Fifty-three isolates
      of B. burgdorferi were confirmed positive with polymerase chain reaction by
      targeting the rrf (5S)-rrl (23S) gene. Using DNA sequencing of the ribosomal
      species-specific rrf (5S) -rrl (23S) intergenic spacer region, all isolates
      belong to the pathogenic genospecies B. burgdorferi sensu stricto (s.s.).
      Nucleotide sequence analysis of a 218- to 220-bp amplicon fragment exhibits six
      cluster patterns and, collectively, these isolates branch into four phylogenetic
      cluster groups for both untraveled, mammalian hosts and those with travel to the
      northeastern United States (New Jersey and New York). Four of five geographic
      regions in Ontario had strain variants consisting of three different genomic
      cluster groups. Overall, our molecular characterization of B. burgdorferi s.s.
      shows genetic heterogeneity within Ontario and displays a connecting link to
      common strains from Lyme disease endemic areas in the northeastern United States.
      Moreover, our findings of B. burgdorferi in I. scapularis reveal that people and
      domestic animals may be exposed to Lyme disease vector ticks, which have wide
      ranging distribution in eastern and central Canada.

PMID- 16892638
TI  - Evaluation of potential role of Anopheles ziemanni in malaria transmission in
      western Kenya.
AB  - Observations of considerable numbers of Anopheles ziemanni Grunberg resting
      inside human dwellings in Ahero, western Kenya, raised the question of its status
      in malaria transmission. To address this question, samples of this species were
      tested for Plasmodium falciparum infection rates and blood-feeding pattern, and
      data were compared with those of known vectors in the area. Although no An.
      ziemanni mosquitoes were infected with P. falciparum sporozoites, the proportions
      of this mosquito species among all anophelines captured and its human blood index
      compared well with those of other vectors, suggesting a possible role in the
      transmission of malaria. Additional studies, including both indoor- and outdoor
      resting mosquito populations as well as incorporating laboratory-based parasite
      susceptibility tests should clarify the situation.

PMID- 16892639
TI  - Spatiotemporal Bayesian analysis of Lyme disease in New York state, 1990-2000.
AB  - Mapping ordinarily increases our understanding of nontrivial spatial and temporal
      heterogeneities in disease rates. However, the large number of parameters
      required by the corresponding statistical models often complicates detailed
      analysis. This study investigates the feasibility of a fully Bayesian
      hierarchical regression approach to the problem and identifies how it outperforms
      two more popular methods: crude rate estimates (CRE) and empirical Bayes
      standardization (EBS). In particular, we apply a fully Bayesian approach to the
      spatiotemporal analysis of Lyme disease incidence in New York state for the
      period 1990-2000. These results are compared with those obtained by CRE and EBS
      in Chen et al. (2005). We show that the fully Bayesian regression model not only
      gives more reliable estimates of disease rates than the other two approaches but
      also allows for tractable models that can accommodate more numerous sources of
      variation and unknown parameters.

PMID- 16892640
TI  - Prey and feeding behavior of larval Culex (Lutzia) fuscanus (Diptera: Culicidae)
      in Shantou, Guangdong Province, China.
AB  - Six taxa of prey were identified from the gut contents of 973 Culex (Lutzia)
      fuscanus Wiedemann (Diptera: Culicidae) larvae collected from 19 sites in
      Shantou, Guangdong Province, China, from May to October 2004. Chironomidae were
      found in the guts of 78.6% of Cx. fuscanus larvae but mosquito larval remains in
      only 2.5%. The junction between prey head and thorax was the most frequent attack
      site in field (125/169 = 73.9%) and laboratory (187/260 = 71.9%) observations.

PMID- 16892641
TI  - Ultrasonographic measurement of upper eyelid thickness in Korean children with
      epicanthus.
AB  - PURPOSE: Upper eyelid thickness was measured to determine whether there is a
      difference in the thickness of the upper eyelids in children with and without
      epicanthus. METHODS: Children were enrolled into the epicanthus group or non
      epicanthus (control) group. The children with epicanthus were classified into
      four subgroups according to the Duke-Elder's classification. The thickness of the
      upper eyelid was measured at five points with A-scan ultrasonography. RESULTS:
      There was no significant difference in upper eyelid thickness between the
      epicanthus group and control group (P > 0.05) or between the subgroups of the
      epicanthus group (P > 0.05). CONCLUSIONS: This result suggests that the etiology
      of epicanthus may not be hypertrophy of soft tissue.

PMID- 16892642
TI  - Thyroid associated orbitopathy following periocular surgery.
AB  - PURPOSE: To descirbe a series of patients in which Thyroid Associated Orbitopathy
      (TAO) occurred after periocular surgery. METHODS: A retrospective case review of
      patients who developed TAO in close temporal association with periocular surgical
      interventions and presented at the orbital clinic from 1997 to 2004. History of
      previous thyroid abnormality and the lack of TAO signs and symptoms before
      surgery were reviewed and analyzed. RESULTS: Nine patients that developed TAO in
      association with periocular surgery were identified. All were women with an
      average age of 59.3years. (range: 45-75 years). The patients divided into two
      groups. Group 1 consisted of four patients who had previously been diagnosed with
      Graves' hyperthyroidism (GH). They ranged in age from 48 to 75 years (average:
      58.8 years). The diagnosis of GH had been made an average of 50.5 months (range:
      12-96 months) before presentation with TAO. Group 2 consisted of five patients
      who had no previous history of thyroid abnormality. They ranged in age from 45 to
      74 years (average: 60.2 years). No patients had any signs or symptoms of TAO
      before their recent presentation. CONCLUSIONS: Periocular surgery may lead to
      local inflammatory events that may contribute to the instigation of TAO in
      predisposed individuals.

PMID- 16892643
TI  - Visual improvement in high myopic amblyopic adult eyes following phakic anterior
      chamber intraocular lens implantation.
AB  - PURPOSE: To evaluate the efficacy and safety of angle-supported phakic anterior
      chamber intraocular lenses in amblyopic adult eyes with very high myopia.
      METHODS: We evaluated 12 eyes in nine patients with very high myopic amblyopia
      who received angle-supported phakic intraocular lenses (Phakic 6H) and followed
      them for more than six months. Uncorrected visual acuity (UCVA), best-corrected
      visual acuity (BCVA), and complications were evaluated. A satisfaction score was
      rated by patients using a 5-point (1-5) numeric scale. RESULTS: The mean age of
      patients was 37.3 +/- 9.4 years, ranging from 29 to 59 years old. The
      preoperative mean refraction (spherical equivalent, SE) was -20.10 +/- 5.41
      diopters (D). The postoperative mean refraction (SE) was -1.75 +/- 0.76 D at six
      months. The postoperative BCVA improved an average 3.92 +/- 1.24 lines over
      preoperative values, and mean endothelial cell loss was 8.9% at six months.
      Development of cataracts, glaucoma, and pupil abnormalities were not demonstrated
      in any case during the study. The patients were all very satisfied, as the
      average satisfaction score was 4.3. CONCLUSIONS: This study indicates that angle
      supported phakic anterior chamber intraocular lens implantation may be an
      effective surgical alternative for the correction of amblyopic adult eyes with
      very high myopia. However, long-term evaluation is necessary to assess possible
      complications and long-term safety.

PMID- 16892644
TI  - Laser photocoagulation as adjuvant therapy to surgery for large macular holes.
AB  - PURPOSE: To evaluate the effectiveness of laser photocoagulation as adjuvant
      therapy in the treatment of large macular holes. METHODS: A randomized clinical
      trial. Thirty-one eyes from 29 subjects with idiopathic macular holes of
      diameters larger than 400 microm were randomized into a laser group and a control
      group. All eyes underwent vitrectomy with peeling of the internal limiting
      membrane. Contrary to the control group eyes, the laser group eyes underwent
      laser photocoagulation at the center of the macular hole before vitrectomy.
      Visual acuity and anatomic outcomes assessed by optical coherence tomography
      (OCT) were analyzed 3 months after surgery. RESULTS: On postoperative OCT,
      closure of the macular hole was noted in 17 of the 18 (94.4%) laser group eyes
      and 10 of the 13 (76.9%) control group eyes. Hole closure without bare retinal
      pigment epithelium was observed in 16 eyes in the laser group and 6 eyes in the
      control group (P < 0.05). The amount of improvement in logMAR visual acuity 3
      months after surgery was 0.40 +/- 0.29 in the laser group, and 0.19 +/- 0.23 in
      the control group (P < 0.05). CONCLUSIONS: Laser photocoagulation constitutes a
      potent adjuvant therapy that may improve anatomical and visual outcomes of
      surgery for macular holes larger than 400 microm.

PMID- 16892645
TI  - Triamcinolone-induced intraocular pressure elevation: intravitreal injection for
      macular edema and posterior subtenon injection for uveitis.
AB  - PURPOSE: To assess the effect of intravitreal and posterior subtenon injections
      of triamcinolone acetonide (TA) on intraocular pressure (IOP). METHODS: we
      reviewed 42 consecutive eyes after intravitreal TA injection (IVTA) and 43 eyes
      following posterior subtenon TA injection (PSTA). All cases had a minimum follow
      up time of three months. After injection, the value and time of the maximal IOP,
      the amount of IOP elevation and the needs of the medication were assessed.
      RESULTS: The lOP increased significantly (p < 0.001) from 16.3 +/- 2.5 mmHg
      preoperatively to a mean maximum of 21.7 +/- 5.3 mmHg in the IVTA group, and from
      15.3 +/- 4.5 mmHg to 20.6 +/- 3.0 mmHg in the PSTA group. An elevation in the IOP
      of more than 5 mmHg from the baseline lOP was seen in 52.4% of the IVTA group at
      a mean time of 3.1 weeks postoperatively, and 44.2% of the PSTA group displayed
      an IOP elevation at 5.9 weeks. CONCLUSIONS: Both developed significant elevations
      of IOP, but this appeared at a later date in the PSTA group. Careful follow-up
      after local injection of steroids is necessary.

PMID- 16892647
TI  - Recurrent intraocular pressure elevation during hemodialysis in a patient with
      neovascular glaucoma.
AB  - PURPOSE: To report a patient with symptomatic intraocular pressure (lOP)
      elevation in an eye with neovascular glaucoma (NVG) during hemodialysis. METHODS:
      Case report. RESULTS: Recurrent episodes of severe ocular pain and elevated IOP
      in the NVG eye were noted during hemodialysis in a 29-year-old man. The patient
      was recently diagnosed at our ophthalmology clinic with NVG due to central
      retinal vein occlusion. IOP was temporarily controlled after the Ahmed valve
      implantation. However, after the fibrous membrane developed and occluded the tip
      of the Ahmed valve, IOP elevation during hemodialysis recurred. Further
      treatments with intravenous mannitol, oral carbonic anhydrase inhibitor, topical
      antiglaumatic agents and subconjunctival 5-fluorouracil (5-FU) injections all
      failed to control relapsing pain and IOP elevation. Eventually, evisceration and
      hydroxyappatite implantation were performed. CONCLUSIONS: Physicians must be
      alert to the possibility of IOP elevation in glaucomatous eyes during
      hemodialysis.

PMID- 16892646
TI  - Distribution and characteristics of peripheral anterior synechiae in primary
      angle-closure glaucoma.
AB  - PURPOSE: To evaluate the characteristics of peripheral anterior synechiae (PAS)
      in primary angle-closure glaucoma (PACG). METHODS: We reviewed the charts of 155
      patients (244 eyes) with PACG. We divided these patients into one of four
      clinical subtypes: acute angle-closure glaucoma (ACG), chronic ACG, angle-closure
      hypertension, and ACG suspect. The prevalence, extent, and location of PAS were
      evaluated according to PACG subtypes. Correlation analysis was used to evaluate
      relationships between the highest IOP level without treatment and the extent of
      PAS. RESULT: The average degree of angle-closure with PAS was 14.6 +/- 9.1 in
      eyes that were classified as ACG suspect, 83.8 +/- 48.3 in angle-closure
      hypertension, 140.5 +/- 31.3 in acute ACG, and 180.3 +/- 31.9 in chronic ACG
      (ANOVA test, P < 0.05). PAS was most frequently found in the superior part of the
      eye, especially from 12 to 1 o' clock. The incidence of broad PAS (PAS over 30
      degrees in width) was highest in superior part, but the medium and narrow PAS
      (PAS limited to within 30 degrees in width) was distributed throughout all 12
      sectors relatively equally. Prior to a laser iridotomy (LI) and other medical
      treatments, a positive correlation was found between the highest IOP (intraocular
      pressure) levels and the extent of PAS in chronic ACG (r = 0.423, P < 0.0001).
      However, statistically significant relationships were not found between the
      highest IOP levels before treatment and the extent of PAS in any of the other
      clinical subtypes. CONCLUSIONS: Our results suggest that acute and chronic ACG
      patients are most likely to have a greater extent of PAS than patients in the
      angle-closure hypertension or ACG suspect subtypes. PAS may be narrower in
      earlier stages and broader in later stages. PAS was also found most frequently in
      the superior part of the eye. The extent of synechial closure of the angle may
      play a role in raising IOP levels in later stages of the disease rather than
      early on.

PMID- 16892648
TI  - Lens-sparing vitrectomy for stage 4 and stage 5 retinopathy of prematurity.
AB  - PURPOSE: To describe the results of lens-sparing vitrectomy for the correction of
      retinal detachment associated with retinopathy of prematurity (ROP) and its
      associated complications. METHODS: Seventeen patients who underwent a lens
      sparing vitrectomy for stage 4 and stage 5 ROP with plus disease at Seoul
      National University Children' s Hospital between 1999 and 2003 were enrolled in
      this study. The patients who had bilateral retinal detachment of ROP underwent a
      lens-sparing vitrectomy in one eye and a scleral buckling surgery or lensectomy
      vitrectomy in the other eye. The patients who had a retinal detachment in one eye
      and a regressed ROP in the other eye underwent unilateral lens-sparing
      vitrectomies. A review of their preoperative clinical findings (including the
      status of retinal detachment and plus disease), post-operative results, and any
      complications encountered was performed. RESULTS: In 17 patients, the
      postoperative success rate of lens-sparing vitrectomy was 58.8%. However, lens
      sparing vitrectomy as a treatment for stage 5 ROP (25.0%) produced more negative
      post-operative results than it did when used to treat either those for stage 4a
      (75,0%) or 4b (66.7%) ROP. Among the 10 eyes in which the retina was attached,
      form vision was shown in six eyes, light could be followed by three eyes, and no
      light perception was present in one eye. Intra- and post-operative complications
      included retinal break formation, cataracts, vitreous hemorrhages, and glaucoma
      in patients with stages 4b and stage 5 ROP. CONCLUSIONS: Lens-sparing vitrectomy
      resulted in encouraging surgical outcomes in the correction of retinal detachment
      of ROP, especially in stage 4 patients. Therefore, a lens-sparing vitrectomy for
      stage 4 ROP patient may be beneficial, although it is still associated with some
      intra- and post-operative complications.

PMID- 16892649
TI  - Antielevation syndrome after unilateral anteriorization of the inferior oblique
      muscle.
AB  - PURPOSE: To report antielevation syndrome with restriction of elevation on
      abduction in the operated eye and overaction (OA) of the inferior oblique muscle
      (IO) of the contralateral eye after unilateral IO anteriorization (AT). METHODS:
      Medical records were reviewed retrospectively in 8 of 24 patients who underwent
      unilateral IOAT. Four patients were referred from other hospitals after the same
      surgery. RESULTS: Four patients had infantile esotropes. The rest showed
      accommodative esotropia, superior oblique palsy, exotropia, and consecutive
      exotropia. The mean amount of hyperdeviation was 16.3 PD (10 approximately 30).
      The mean restriction of elevation on abduction in the operated eye was -1.6 (-1
      approximately -4) and IOOA of the contralateral eye was +2.7 (+2 approximately
      +3). IOAT of nonoperated eyes in 4 patients, IO weakening procedure of
      anteriorized eyes in 2 patients, and IO myectomy on an eye with IOAT in 1 patient
      were performed. Ocular motility was improved after surgery in all patients.
      CONCLUSIONS: Unilateral IOAT may result in antielevation syndrome. Therefore
      bilateral IOAT is recommended to balance antielevation in both eyes. A meticulous
      caution is needed when performing unilateral IOAT.

PMID- 16892650
TI  - Two cases of uveal effusion syndrome.
AB  - PURPOSE: To report a case of uveal effusion syndrome associated with hypotony and
      a case of uveal effusion syndrome in nanophthalmos. METHODS: The first case was a
      25-year-old man who presented with decreased visual acuity in the left eye and
      hypotony. Fundus examination revealed choroidal effusion and retinal detachment
      with a thickened eyeball. Partial thickness sclerotomy and sclerectomy were
      performed. The second case was a 13-year-old boy who had uveal effusion syndrome
      with a nanophthalmic eye. RESULTS: In the patient with hypotony, intraocular
      pressure was well maintained following partial thickness sclerotomy and
      sclerectomy, and choroidal effusion and retinal detachment were reduced. The
      visual acuity of the nanophthalmic patient was well maintained during a 3-year
      follow-up period without treatment. CONCLUSIONS: appropriate treatment modalities
      should be considered depending on the ophthalmic condition of the individual
      patient.

PMID- 16892651
TI  - Multiple retinal hemorrhage following anterior chamber paracentesis in uveitic
      glaucoma.
AB  - PURPOSE: We describe the occurrence of a massive retinal hemorrhage following
      anterior chamber paracentesis in uveitic glaucoma. METHODS: A 33-year-old man who
      suffered from uveitic glaucoma was transferred to our hospital. The lOP in both
      his eyes was documented to vary between 11 mmHg and 43 mmHg and remained at a
      continuously high level for 7 months despite maximally tolerable medical
      treatment. A paracentesis was performed bilaterally to lower the IOP. RESULTS:
      Immediately after the paracentesis, massive retinal hemorrhages occurred in the
      left eye. Multiple round blot retinal hemorrhages with white centers occurred in
      the equator and peripheral retina, and small slit hemorrhages were observed in
      the peripapillary area. A fluorescence angiography(FAG) showed no obstruction of
      retinal vessels but a slightly delayed arteriovenous time in the left eye.
      CONCLUSIONS: It is important to be aware that patients who have a persistent
      relatively high IOP are at an increased risk of developing decompression
      retinopathy due to paracentesis and filtering surgery.

PMID- 16892652
TI  - Surgical management of bilateral exudative retinal detachment associated with
      central serous chorioretinopathy.
AB  - PURPOSE: To report a case of bilateral bullous exudative retinal detachment in
      central serous chorioretinopathy (CSC) which was attached by vitrectomy and
      internal drainage of the subretinal fluid. METHODS: A 47-year-old man affected by
      bilateral atypical CSC with a bullous retinal detachment with subretinal exudate.
      A fluorescein angiogram (FAG) showed multiple points of leakage and staining of
      subretinal fibrosis. A tentative diagnosis of Vogt-Koyanagi-Harada (VKH) syndrome
      was made and the patient was treated with systemic corticosteroids and
      immunosuppressive agents. However, the subretinal fluid was not absorbed. He was
      then treated with vitrectomy and internal drainage of subretinal fluid. RESULTS:
      The retina was attached successfully in both eyes. Visual acuity improved to
      20/50 in his left eye but did not improve in the right eye due to subretinal
      fibrotic scarring and atropic changes on the macula. CONCLUSIONS: Our case
      suggests that the surgical management of bullous exudative retinal detachment is
      safe and necessary.

PMID- 16892654
TI  - Pyoderma gangrenosum complicated with myelodysplastic syndrome followed by
      rapidly progressing pyothorax-associated lymphoma: a case report.
AB  - This report describes a patient with pyoderma gangrenosum (PG) complicated with
      myelodysplastic syndrome (MDS) followed by rapidly progressing pyothorax
      associated lymphoma (PAL). A 74-year-old man was admitted with cutaneous gangrene
      associated with MDS. We diagnosed him as having PG, and high-dose oral
      prednisolone was started. Two months after admission he developed lymphoma
      rapidly. The patient died in spite of radiation therapy. On autopsy, the
      pathological diagnosis was diffuse large cell lymphoma. Epstein-Barr virus (EBV)
      encoded RNA, and EBV-encoded nuclear antigen (EBNA) were detected in lymphoma
      cells. This case suggested that immunosuppressive therapy might favour the clonal
      proliferation of EBV-infected cells.

PMID- 16892653
TI  - Visual loss in one eye after spinal surgery.
AB  - PURPOSE: To report a patient who developed an unusual combination of central
      retinal artery occlusion with ophthalmoplegia following spinal surgery in the
      prone position. METHODS: A 60-year-old man underwent a cervical spinal surgery in
      the prone position. Soon after recovery he could not open his right eye and had
      ocular pain due to the general anesthesia. Upon examination, we determined that
      he had a central retinal artery occlusion with total ophthalmoplegia. RESULTS:
      Despite medical treatment, optic atrophy was still present at the following
      examination. Ptosis and the afferent pupillary defect disappeared and ocular
      motility was recovered, but visual loss persisted until the last follow-up.
      CONCLUSIONS: A prolonged prone position during spinal surgery can cause external
      compression of the eye, causing serious and irreversible injury to the orbital
      structures. Therefore, if the patient shows postoperative signs of orbital
      swelling after spinal surgery the condition should be immediately evaluated and
      treated.

PMID- 16892655
TI  - [Estimation of time of death by the use of the overwintering of flies].
AB  - We observed whether or not there were eggs, larvae, pupae, and empty pupal shells
      of flies on cadavers found outdoors in Sapporo, the northern district of Japan
      (43 degrees N). The temperature has an influence on the oviposition of flies. The
      average season in which flies lay eggs is from the middle of April to the
      beginning of November, although there is a little lag year by year. As flies
      overwinter generally as larvae, we can estimate postmortem interval of a cadaver
      found in spring on the basis of the size and the mortality of the larvae. If the
      length of larvae is 1 cm or longer, and many of them are dead, and if there are
      no empty pupal shells, the time of death of a cadaver found outdoors in spring is
      between the middle of September and the beginning of November in the previous
      year.

PMID- 16892656
TI  - Medicare part D in long-term care: special consideration for the vulnerable
      elderly nursing facility resident.

PMID- 16892657
TI  - The economic burden of intracerebral hemorrhage: evidence from managed care.
AB  - Data from the Integrated Healthcare Information Services managed care database
      were used to estimate per-patient costs of intracerebral hemorrhage (ICH) for up
      to one year after an initial ICH event. Plan enrollees (age > or = 18 yr)
      hospitalized with a primary International Classification of Diseases, Ninth
      Revision, Clinical Modification diagnosis of ICH (431.xx) during July 1999 to
      June 2002 were selected. Resource utilization/costs associated with the initial
      hospitalization were calculated for all patients. Postdischarge use/cost of
      health care services (repeat hospitalization, skilled nursing/rehabilitation
      services, outpatient use, pharmacy) were estimated for up to 365 days after
      hospital discharge for patients surviving the initial stay. Forty-six percent of
      the 493 patients selected were at least 65 years of age and 60% had private
      health insurance. Patients who died during their initial ICH hospitalization (N =
      189 [38.4%]) incurred average treatment costs of $16,466. Survivors incurred
      initial hospitalization costs of $28,360 and first-year postdischarge costs of
      $16,035. Among survivors, 8% had repeat hospitalizations and 41% required
      inpatient skilled nursing/rehabilitation. Treatment costs for ICH to private
      payers appear to be considerable and may reflect a sizable long-term financial
      burden to U.S. health plans.

PMID- 16892658
TI  - Improving glycemic control: the case for self-monitoring blood glucose levels.
AB  - Diabetes can be potentially identified, monitored, treated, and prevented more
      easily now than at any other time in history. Yet, the prevalence of diabetes
      continues to grow and the complications associated with it continue to afflict
      millions of Americans. Glycemic control, or the maintenance of appropriate levels
      of blood sugar, measured through the self-monitoring of blood glucose or a
      glycated hemoglobin test, represents the best opportunity for persons with
      diabetes to prevent complications by helping them understand the effect of their
      lifestyle choices and medications on their health. Despite the numerous
      advantages of glycemic control, a number of barriers prevent individuals from
      monitoring their blood sugar concentrations and achieving the health benefits
      that come with the proper understanding of their condition.

PMID- 16892659
TI  - Cost analysis of psoriasis treatments.

PMID- 16892660
TI  - Would elimination of copayments for phototherapy decrease the cost of treating
      psoriasis with systemic biologics? A cost analysis.
AB  - Phototherapy is a proven treatment method for the treatment of psoriasis, yet is
      typically underutilized because of the frequency of physician visits and
      copayments required for each session (typically 2-5 treatments/wk). Injectable
      biologic therapies are effective but costly. The objective of this study was to
      explore how changes in copayment strategies for phototherapy may affect biologic
      usage. Published estimates of the cost of phototherapy and biologic treatment
      were used to determine the costs of these treatments to patients and insurers.
      With an estimated patient copayment of $30 per office visit and a pharmacy
      copayment of $50 per month, the $1,800 annual patient expense for phototherapy
      far exceeds the estimated out-of-pocket expenses for etanercept, alefacept, and
      efalizumab ($840, $405, and $780, respectively). The estimated annual costs to
      MCOs ranged from $3,008 for phototherapy, to $20,300 for etanercept. Copayments
      for phototherapy may be shifting patients toward biologic treatment, which is
      more convenient but more costly to managed care plans.

PMID- 16892661
TI  - What happened to the role of pharmacists in disease state management?

PMID- 16892662
TI  - The effect of implementing a mental health-medical benefit parity-of-coverage
      mandate.

PMID- 16892663
TI  - Needs assessment.

PMID- 16892664
TI  - Metabolic syndrome.

PMID- 16892665
TI  - Keeping participants enrolled: participation.

PMID- 16892666
TI  - Teaching and learning practice development for change.
AB  - The current expectation in health care for nurses to use research evidence when
      making decisions about patient care practices requires a change in the culture of
      nursing service delivery. There are many different approaches to support this
      change. One approach frequently referred to in contemporary literature is
      practice development, which aims not just for understanding and acquiring new
      knowledge, but also for implementing change by improving clinical practice and
      increasing effectiveness in patient care. Its success depends on skilled change
      agents or facilitators. This article discusses strategies used in a workshop to
      educate and prepare practice development facilitators for effecting change.

PMID- 16892667
TI  - Registered nurses and unlicensed assistive personnel: an uneasy alliance.
AB  - To meet challenges of continuing change in the health care industry and maintain
      organizational viability in increasingly competitive markets, the use of the
      registered nurse--unlicensed assistive personnel model is an undeniable reality
      that fills the void created by the current shortage of nurses and decreases the
      costs of providing patient care. Although much has been published about the need
      for nurses to delegate and supervise patient care-related activities, little has
      been written about the skills needed to do this effectively or how these skills
      may be learned. Academic and clinical educators must find ways to facilitate the
      development of delegation and supervision abilities as nurses increasingly work
      with nonprofessional staff. Continuing education is an effective way for nurses
      to learn the skills required by changing models of patient care delivery and
      evolving professional roles.

PMID- 16892669
TI  - Overcoming burnout: how to revitalize your career.
AB  - Burnout is becoming increasingly common in the health care profession. Indicators
      of burnout include feeling overworked, frustrated, emotionally drained, and less
      productive. Burnout leads to interpersonal conflicts, physical symptoms,
      compulsive activities, decreased productivity, and negative emotions. Individuals
      who experience burnout believe they cannot change their situation. Job burnout
      can be overcome after the cause is pinpointed. To revitalize a career and move
      away from a burnout state, individuals need to change their thought processes and
      viewpoints about the people and things that may be contributing to their burnout.

PMID- 16892668
TI  - Increasing nurses' knowledge and skills for enhanced response to intimate partner
      violence.
AB  - BACKGROUND: A theoretically based intimate partner violence in-service program
      was developed, implemented, and evaluated among public health nurses. METHODS: A
      two-phase, mixed-methods design was used. Phase 1 used qualitative methods for
      content development of the in-service program. Phase 2 used a one-group pretest
      posttest design to evaluate the effectiveness of the program. RESULTS: In Phase
      1, nurses perceived a need for knowledge about community intimate partner
      violence prevention resources and enhancement of interviewing skills. In Phase 2,
      no significant difference was noted in level of intimate partner violence
      knowledge between pretest and posttest (p < .107). However, a significant
      difference in skill level was noted between pretest and posttest (p < .003).
      CONCLUSIONS: Results support the use of an in-service program as an effective
      method of enhancing the intimate partner violence clinical skills of nurses.

PMID- 16892670
TI  - Re-entry into the registered nursing work force: we did it!
AB  - Because the enrollment in nursing programs dropped in the late 1990s and
      healthcare agencies and education programs were seeking ways to increase the
      numbers of nurses, Bethel College in Mishawaka, Indiana, and Memorial Hospital in
      South Bend, Indiana, designed a plan to encourage nurses who had been out of
      nursing to re-enter the work force. This article details the steps used in this
      partnership and demonstrates a process for helping registered nurses to return to
      nursing. In the 6-credit, 8-week course, nurses were prepared to function on a
      medical-surgical unit by reviewing important concepts related to nursing
      practice, physical assessment, nursing process, nursing skills, pharmacology, and
      clinical nursing update. It was anticipated that receiving college credit for the
      course would be a motivator for returning to study at the registered nurse to
      bachelor of science in nursing level. With 2 full clinical days each week, the
      students could experience a normal work shift and the routine of a busy clinical
      unit.

PMID- 16892671
TI  - Research in nursing: for an ethical pedagogy!

PMID- 16892672
TI  - [Beliefs of undergraduate nursing students on aging].
AB  - The objective of this study was to identify the conceptions of undergraduate
      Nursing students on aging. A qualitative research was carried at the Cidade de
      Sao Paulo University (Unicid); 49 students were requested to write a text whose
      theme was "what does being old mean?". The texts were submitted to a content
      analysis, in which three thematic units were identified: Representations of the
      old being; How respondents perceive old the elder in society and within the
      family; and the Need to change public opinion regarding aging. The results showed
      that conceptions of the students on aging are tied to negative images and showed
      the need for changes in the society and in the family.

PMID- 16892673
TI  - [Directed study as a teaching strategy in nursing education].
AB  - This is a descriptive exploratory study aimed at evaluating directed study as a
      teaching strategy used in professional education. Data was collected by means of
      a questionnaire applied to 14 students attending a Practical Nursing course;
      their answers were examined according to Bardin. The strategy was considered good
      (86%). Eighty-three semantic units were identified in the analysis of the
      answers, classified as: advantages (53%); not "nice" (16%); difficulties (7%);
      feelings (12%); and suggestions (12%). In addition, subjects considered as
      didactic educational purposes of direct study to allow the development of topics
      that interest the student; to stimulate pleasure in studying; and to encourage
      the student to be the subject of his own learning process. The authors consider
      directed study a good teaching strategy, with features that demand skills and
      competences from teachers and students in order to obtain satisfactory results in
      the teaching-learning process.

PMID- 16892675
TI  - [Leisure activities for the elderly during hospitalization].
AB  - This study intended to: 1. Identify the leisure activities available in the
      hospital and those in which the elderly participate; 2. Relate elderly
      hospitalization with their participation in leisure activities; 3. Assess the
      factors that motivate and inhibit elderly participation in leisure activities.
      This is a descriptive/exploratory study carried out with one hundred hospitalized
      elderly patients. Available leisure activities were television and magazines.
      Most participants (99%) said they participate in leisure activities such as
      family/ friends conversations and visits. Involvement in leisure activities
      decreases with associated diseases and increases with hospitalization time.
      Leisure was motivated by the elderly's personal characteristics, the reduction of
      the hospitalization's negative effects, and the benefits it brings to the health.
      Its limitation was associated to intrinsic aspects of the elderly and to the
      institutional context.

PMID- 16892674
TI  - [Experiences of women in face of pain from acute myocardial infarction].
AB  - The aim of this study was to understand the meanings of the experience of pain
      suffered by women during acute myocardial infarction (AMI) and to identify their
      immediate actions in face of pain. This qualitative research used the Symbolic
      Interactionism theory and the Grounded Theory methodology. Forty-three women were
      interviewed at the University Hospital. The central category expressing the pain
      experience was that it was "a break with day-to-day life". The categories that
      expressed such break revealed that in face of increasing pain those women felt
      dominated and afraid of dying because they had lost control over their bodies and
      their lives. They did not recognize the occurrence of AMI and at first resisted
      to look for assistance by attempting to alleviate the pain. In face of the
      unbearable pain and their impotence to control it, they asked for God's salvation
      and help from surrounding people and finally resorted to medical assistance.

PMID- 16892676
TI  - [Mental and behavioral disturbances in the hospital information system:
      perspectives for nursing].
AB  - The purpose of this study was to explore some of the possibilities of getting
      information about mental and behavior disorders using the Internet, specifically
      at the Ministry of Health's DATASUS website. The site presented elements that
      illustrate the Health Information Systems' resources, which may be used by nurses
      as a safe and simplified way of obtaining data. The study focused on psychiatric
      hospitalization through the SIH-SUS in the city of Ribeirao Preto, State of Sao
      Paulo. Given the nurses' needs to use technological resources that can contribute
      for the organization of the service and the analysis of the situation of the
      mental and behavior disorders, SIH-SUS data are a possible instrument to start
      the analysis whose results may make possible important and effective changes for
      the management of the services, in search for quality in mental and psychiatric
      health assistance.

PMID- 16892677
TI  - [Comparisons among measurement tools in traumatic brain injury outcomes].
AB  - Traumatic brain injury (TBI) is considered the most important cause of disability
      among young people and the most common neurological cause of morbidity.
      Consequently, there is increasing interest in scales to monitor recovery in TBI.
      Among these scales, two have been widely adopted: the Glasgow Outcome Scale (GOS)
      and the Disability Rating Scale (DRS). The purpose of this paper is to compare
      the results found in DRS and in the original and extended GOS. Sixty-three closed
      head injury victims, aged between 12 and 65, on an outpatient follow-up program
      at a trauma center in the city of Sao Paulo, with 6 months to 3 years post-TBI,
      had their characteristics and outcomes assessed. When comparing the results
      obtained by the scales, it was concluded that although the three of them were
      strongly correlated, extended GOS showed to be more sensitive in detecting
      changes in victims with better post-traumatic conditions.

PMID- 16892678
TI  - [Nursing auxiliaries and technicians and hospital infection control in surgical
      centers: myths and truths].
AB  - This analytical and descriptive study is aimed at detecting concepts that
      translate myths and truths on hospital infection among nursing auxiliaries and
      technicians at the surgical centers of three hospitals. The data collection
      instrument consisted of 28 affirmative statements (15 true and 13 false)
      encompassing factors related to the patient, the surgical team, the environment,
      and procedures. The statements contain a three-point scale (I agree, I am in
      doubt, I disagree). We received 72% of adequate answers and 28% of non-adequate,
      which indicates that perioperative nursing professionals have satisfactory
      knowledge of hospital infection control. In the items use of safety footwear,
      rings and other objects, hair as a pathogen, hand scrubbing, use of humid gown
      and surgical area, infected surgery and cleaning routine, occupational diseases,
      hospital infection, surgical site infection and surgery time we were able to
      detect myths and rituals about infection control, which are mainly related to the
      culture of those who practice them, thus perpetuating resistance to change.

PMID- 16892679
TI  - [The humanization process of the hospital environment centered around the
      worker].
AB  - The humanization of the hospital environment cannot be achieved if the focus is
      directed only to external motivational factors or just to the user. A
      humanization program needs to be assumed as a participative construction process
      that demands respect and valuing of the human being that provides care. Based on
      human and ethics values and principles and on Freire's ideas, this study aims to
      describe how a humanization process was unchained in a hospital, initially
      centering on the worker, through the collective discussion of concrete problems
      and the construction of horizontal, reflective dialogical relations. The proposal
      made possible a better comprehension of the meaning of humanization, with the
      rescue of previous initiatives of humanization, the elaboration of a databank in
      which there is room for subjectivity, the creation of warm collective areas and a
      closer relationship between directors and workers.

PMID- 16892680
TI  - [Teaching of gerontogeriatric nursing and complexity].
AB  - The present study had the objectives of identifying the characteristics of
      gerontogeriatric nursing and of reflecting on this teaching, based on identified
      characteristics, in the light of Complexity. A qualitative research, its data
      sources were nine proceedings volumes of Brazilian Nursing congresses and seven
      Brazilian nursing publications of the 1991-2000 period. The main body of this
      article was comprised of 16 scientific articles; QRSNUD* IST4 was used for
      analysis. Results showed that this teaching does take place, and it is carried
      out through: mandatory disciplines in the curriculum; practical activities;
      activities during curricular training; extra-curricular activities; participation
      on specific or general Nursing events in which studies are presented; other
      activities. To use the principles of Complexity is tantamount to perceiving
      educative teaching as trying to convey a culture that will enable future workers
      to understand the human condition and to think in a contextualized, open,
      globalized, ethical way.

PMID- 16892681
TI  - [Calculation of the reprocessing costs of single-use tongs used in video-assisted
      surgeries].
AB  - The frequent reuse of disposable forceps instruments is justified by their high
      cost. However, few studies have been carried out on this topic. The objective of
      this study was to develop a methodological proposal for calculating the
      reprocessing costs for these instruments used in video-assisted surgery. A
      flowchart was developed for each phase of the reprocessing. This allowed
      subsequent identification of the cost components in terms of labor, materials and
      indirect expenses. From these data, a methodological proposal for cost
      calculation could be created, based on the Full Absorption Costing Method,
      including the spreadsheet for data collection.

PMID- 16892682
TI  - [Consequences of medical errors in intensive and semi-intensive care units].
AB  - This report was aimed at characterizing medication errors and evaluating their
      consequences for the patients' conditions and for the nursing workload in the
      Intensive Care Units (ICU) and Semi-Intensive Care Units (SICU) of two hospitals
      in the city of Sao Paulo. The sample was 50 patients, and data was gathered in
      record logs. The severity of the conditions and the nursing workload were
      assessed before and after the occurrence. Out of a total of 52 medication errors,
      12 (23.80%), were non-administration of dosage, 11 (21.15%) were wrong
      medication, and 9 (17.31%) excessive dosage. There were no changes in patient
      conditions (p=0.316), but the nursing workload increased (p=0.009). As for the
      medication group, i.e, potentially dangerous or non-dangerous, there were no
      statistically significant differences either in the severity of the patients
      (p=0.456) or in the nursing workload (p=0.264) after the occurrence.

PMID- 16892683
TI  - [Understanding women with advanced gynecological cancer: a Heideggerian
      approach].
AB  - This qualitative phenomenological research was carried out in order to understand
      how women experience living with advance gynecological cancer. We chose to make a
      qualitative survey in a phenomenological approach, based on the following
      directive question: "I'd like you to tell me your experience: 'How is it to be a
      woman with gynecological cancer?" ' Six women were interviewed. The ontological
      unification which emerged from the speeches were analyzed and interpreted
      according to Martin Heidegger's philosophical referential. These unifications
      made possible to see ways to care for these women that go far beyond technical
      and scientific knowledge. It is necessary to understand what has been lived by
      the other, thus ensuring a quality of care that contemplates subjectivity and
      inter-subjectivity.

PMID- 16892684
TI  - [Clinical and psychosocial models of attention to the individual and the family
      in home care--conceptual frameworks].
AB  - Home care is a rapidly expanding segment in Brazil. The model currently applied
      to home care is based on clinical and hospital models. The objective of this
      article is to propose theoretical frameworks that can be applied to home care by
      taking into account its psychosocial dimension. Although indivisible, the
      conceptual frameworks of the clinical and the psychosocial models are broken
      down, for clarity purposes, in order to contribute to the improvement of
      practices, so as to add personal expressions and contexts as elements of
      psychosocial dynamics.

PMID- 16892686
TI  - [Delivery center and obstetric assistance focused on the parturient's needs].
AB  - As an obstetric nurse working in a Delivery Center and considering the studies
      and reflections on the new model of assistance to labor and birth (humanized
      assistance), I started to think about this concept, given the various
      connotations attributed to the term. This article was written with the aim of
      divulging our proposal of replacement of the expression "humanized assistance to
      child-birth" for "obstetric assistance focused on the parturient's needs", and to
      describe the assistance given at the Delivery Center of the General Hospital of
      Itapecerica da Serra, in the Sao Paulo Metropolitan Region, where a protocol of
      obstetric behavior and rules recommended by the Ministry of Health is followed.

PMID- 16892685
TI  - [Evaluation of the implementation of CIPESC in Curitiba].
AB  - This report of experience has the objective of presenting the results of the
      evaluation workshops on the implantation of an operating system of CIPESC, which
      simultaneously describes, validates, quantifies and qualifies the nursing
      practices in collective health carried out in the scope of extra-internment in
      the Units of Health of the city of Curitiba, in the State of Parana. The
      workshops provided subsidies for identification of the strong points and the
      difficulties of implementing the CIPESC-Curitiba nomenclature, but at the same
      time revealed contradictions in the nurses' speeches. It is agreed upon that it
      is through conscious practice that these contradictions are overcome, and,
      starting from them, is built a Nursing with potential of intervention in the
      population's epidemiological profiles.

PMID- 16892687
TI  - [Identification of family vulnerability in clinical practice].
AB  - In this paper we present a report of a clinical situation in which we identified
      the vulnerability of the family, propitiating to pediatric nurses the use of this
      concept in their practice and intervention with families. The study was carried
      out with a family that was going through a situation of a child illness and
      hospitalization. The vulnerability was identified in the interactions of family
      members with the illness, with other family members and with the health staff,
      and served as a guide for planning the nursing assistance. The interventions led
      to the strengthening of the family to face the situation and, for pediatric
      nurses, the recognition of the importance of using the results of theoretical
      research in their professional practice.

PMID- 16892688
TI  - [First episode of schizophrenia and nursing care].
AB  - Schizophrenia is one of the main health problems in current days, requiring
      considerable investment from the health system. Intervening in the first episode
      offers a unique opportunity in the treatment of schizophrenia and influences the
      course of the illness. This article consists of a critical literature review
      aimed at examining knowledge on first episode schizophrenia and discussing the
      contribution of nursing care. A research was carried out in bibliographical
      databases. The data collected made possible the organization of information on
      the general concept of schizophrenia, its first episode, types of intervention
      and nursing performance. We found out that in Brazil there are few studies
      related to first episode schizophrenia in Nursing, few available specialized
      services, and few social resources. This situation reveals the need for more
      studies on first episode schizophrenia.

PMID- 16892689
TI  - [Health care models and the building of nursing knowledge and practice].
AB  - This is a reflective paper focused on the origins and main characteristics of the
      epidemiological and clinical models, their connections with the health care
      models currently adopted in Brazil, and the construction of Nursing knowledge in
      this context. From this perspective, the authors propose a re-thinking of Nursing
      knowledge and practice, pointing out possibilities for expanding the Nursing
      field, as well as the boundaries and challenges to be overcome by the area
      professionals.

PMID- 16892690
TI  - [Characterization of knowledge production on the patient care system in Brazil].
AB  - This is a bibliographical study that has as its aim characterizing the Brazilian
      scientific production on the "Patient Care System" and visualizing its trends. A
      retrospective bibliogra-phical study (1990-2002) was carried out taking into
      consideration the items: date, title of the journal, type of research and
      approach of the publication. Production average was 13.4 publications/ year and
      articles were distributed among 23 journals, with a majority of them dealing with
      hospitals (63.2%). Cardiology was the theme of 17.6% of the articles, and 78.6%
      of them were focused on the implementation, development and evaluation of SAE
      models. NANDA taxonomy was men-tioned in 40.2% of the production, and Wanda Horta
      in 40.5%. There are still some blanks in this area of knowledge, but the
      increasing availability of the scientific production on this subject may help
      professionals in the implementation of the patient care system.

PMID- 16892691
TI  - Why do oncologists prescribe--or not prescribe--conventional chemotherapy to
      geriatric patients with metastatic non-small cell lung cancer?

PMID- 16892692
TI  - Pathophysiology and management of hot flashes.
AB  - Depending on their frequency and severity, hot flashes can be a major source of
      distress for individuals with cancer, particularly women with a history of breast
      cancer and men with prostate cancer. Characterized by increased skin temperature,
      skin conductance, and heart rate, hot flashes are associated with somatic,
      behavioral, and emotional manifestations. In this article, the authors review the
      prevailing theories on the pathophysiology of hot flashes and assess the major
      treatment interventions, such as hormonal agents, nonhormonal pharmacotherapy
      (including antidepressants), and complementary/alternative medicine options.

PMID- 16892693
TI  - More choices, more questions: weighing the options for treating hot flashes.

PMID- 16892694
TI  - Palliative percutaneous drainage in malignant biliary obstruction. Part 2:
      Mechanisms and postprocedure management.
AB  - Malignant biliary obstruction frequently is associated with pruritus, anorexia,
      cholangitis, or hyperbilirubinemia; this difficult complication precludes the use
      of antineoplastic agents that are excreted or metabolized via the liver. In
      patients with low biliary obstruction, endoscopic stent placement may accomplish
      drainage of the entire biliary tree without the need for an external device.
      However, patients with high bile duct obstruction most often require a
      percutaneous approach to drain the target ducts to maximize drainage and to avoid
      draining an atrophic segment or lobe. In the first in this series of two
      articles, the indications for biliary drainage and preprocedure evaluation in
      malignant biliary obstruction were discussed. This second article describes the
      mechanisms of percutaneous biliary drainage and postprocedure management,
      including consideration of possible complications.

PMID- 16892695
TI  - A safe and effective method of palliation.

PMID- 16892696
TI  - Retrospective study of the effect of skeletal complications on total medical care
      costs in patients with bone metastases of breast cancer seen in typical clinical
      practice.
AB  - Intravenous bisphosphonates are effective in reducing the incidence of skeletal
      related events (SREs) in women with bone metastases of breast cancer. The cost
      effectiveness of such therapy depends in part on the potential cost savings
      achieved by preventing these events. However, estimates of the costs of SREs in
      women with bone metastases of breast cancer in typical US clinical practice are
      unavailable. The purpose of this study was to estimate the treatment costs of
      clinically significant SREs and the impact of these events on total medical care
      costs in patients with bone metastases of breast cancer. Data were gathered from
      a large US health insurance claims database. Patients with bone metastases of
      breast cancer who experienced one or more clinically significant SREs in typical
      clinical practice were matched to similar patients without SREs based on
      propensity scores. Kaplan-Meier estimated total medical care costs were compared
      over 60 months for propensity-matched samples of patients with SREs and without
      SREs. We identified 617 patients with breast cancer and bone metastases,
      including 321 (52%) with > or = 1 clinically significant SRE. After matching,
      there were 201 patients each in the SRE and no-SRE groups, with mean follow-up of
      13.8 and 11.0 months, respectively. In the SRE group, costs of treatment of SREs
      were $13,940 (95% CI, $11,240-$16,856) per patient. Total medical care costs were
      $48,173 (95% CI, $19,068-$77,684) greater in SRE versus no-SRE patients (P =
      0.001). The costs of clinically significant SREs in patients with breast cancer
      and bone metastases seen in typical clinical practice are substantial. Treatments
      that reduce the incidence of SREs, such as intravenous bisphosphonates, should
      reduce these costs.

PMID- 16892697
TI  - Managing cancer pain in a 24-hour outpatient cancer center.

PMID- 16892698
TI  - Managing common retinal disorders.

PMID- 16892699
TI  - Caring for the patient with glaucoma.

PMID- 16892700
TI  - Fungial infections: an essential guide.

PMID- 16892701
TI  - Taking action on suspected child sex abuse.

PMID- 16892703
TI  - [Effect of experimental classical swine fever (CSF) infection on libido and
      ejaculate parameters in boars].
AB  - The objective of this study was to characterize the effect of an experimental
      infection with the classical swine fever (CSF) virus on libido and ejaculate
      parameters of adult boars. Four boars 10 month old were infected with a CSF field
      isolate (Visbek/Han95). Semen was collected every second day after infection and
      daily during the pyrexic phase. The only clinical signs in the boars were an
      increase in body temperature, but never above 39.9 degrees C and a temporally
      reduction of food intake. The libido was always good, so semen collection was
      performed in three boars without difficulty and the semen quality was always in
      the range of the minimum requirements for sperm that is used for artificial
      insemination. Although one boar had a good libido only a sperm free ejaculate
      could be collected on one day. The results show that a CSF virus infection of
      adult boars hardly causes any clinical symptoms and that sperm can be obtained
      despite fever. Insemination boars may thus be of special epidemiological
      relevance for the dissemination of the CSF virus.

PMID- 16892705
TI  - [Effects of tannins in animal nutrition].
AB  - Tannins are watersoluble plant polyphenols that precipitate proteins. According
      to their chemical structure they can be divided into condensed tannins and
      hydrolysable tannins. Altogether, tannins are reported to have various
      physiological effects like anti-irritant, antisecretolytic, antiphlogistic,
      antimicrobial and antiparasitic effects. Phytotherapeutically tannin-containing
      plants are used to treat nonspecific diarrhoea, inflammations of mouth and throat
      and slightly injured skins. Studies with ruminants have also demonstrated that
      the denaturing properties of tannins can possibly be used to improve protein
      supply to the small intestine. Besides anthelmintic effects of condensed tannins
      have been observed in sheep and goats. On the other hand high tannin
      concentrations resulted in reduced animal performances and health disorders as
      well in ruminants as in monogastriers. Further scientific research is therefore
      needed to clarify whether tannins can be effectivly used in livestock feeding,
      for example in prophylaxis of diarrhoea or parasitic control.

PMID- 16892704
TI  - [Pulmonary artery wedge pressure and heart rate measurement during
      pharmacological stress induction for left cardial function diagnosis in horses
      with and without heart disease].
AB  - In 18 horses, the pulmonary artery wedge pressure and the heart rate were
      measured during pharmacological stress load. 12 horses were healthy (4 trained, 8
      untrained) and 6 horses had a heart disease (3 trained, 3 untrained).
      Pharmacological stress induction was carried out with the sympathomimetic drug
      dobutamine at a dosage rate of 7.5 microg/kg/min over 10 minutes of infusion. At
      the fourth minute, the parasympatholytic drug atropine was administered (5
      microg/kg bw), and the heart rate and the pulmonary artery wedge pressure were
      continuously measured over 26 minutes. During sole dobutamine infusion, a
      significant decrease in heart rate and a significant increase in pulmonary artery
      wedge pressure were observed. After the application of atropine in the fourth
      minute, a significant increase in heart rate (from 35.7 +/- 6 up to 106 +/- 38/
      min) and in pulmonary artery wedge pressure (from 15.7 +/- 3 up to 24 +/- 8.6
      mmHg) were visible in the group of healthy horses. The horses with heart diseases
      had a significantly higher increase in both parameters (heart rate and pulmonary
      artery wedge pressure) with a significantly positive correlation (r = 0.7). The
      heart rate increased in the horses with heart diseases from 35.2 +/- 2,8
      beats/min up to 132 +/- 45.7 beats/min and the pulmonary artery wedge pressure
      increased from 17.3 +/- 3,2 mmHg up to 32.7 +/- 13 mmHg. The cardiac status
      (healthy or heart disease) as well as the training level of the horses (untrained
      or trained) had a significant influence on the heart rate and the pulmonary
      artery wedge pressure. The untrained horses (healthy and heart disease) showed
      significantly higher values over a longer period of time than did the trained
      horses with the same cardiac status. Additionally the influence of
      pharmacological stress induction on echocardiographic parameters was
      investigated. The left atrial size (p = 0.015) and left ventricular diameter were
      significanly different in the systole (p = 0.008) and in the diastole (p = 0.001)
      between healthy horses and horses with heart diseases. All horses showed a
      positive correlation between the pulmonary artery wedge pressure and the left
      atrial size (r = 0.8), as well as between the left ventricular systolic (r = 0.6)
      and the diastolic diameter (r = 0.6). The correlation between the pulmonary
      artery wedge pressure and the left atrial size was nearly the same in the healthy
      horses (r = 0.74) and in the horses with heart diseases (r = 0.76). Regarding the
      training level, all untrained horses had a significantly higher correlation
      between the pulmonary artery wedge pressure and the left atrial size (r = 0.87)
      in comparison to the trained horses (r = 0.74). Particularly in the untrained
      horses with heart diseases, this correlation was remarcable (r = 0.99).

PMID- 16892706
TI  - [Use of hyaluronic acid cleaving enzymes for absorption acceleration. Results of
      an in vitro study with xylazine and ketamine].
AB  - The so-called "Hellabrunner Mischung", (combination of xylazine and ketamine with
      hyaluronidase) is frequently used for the immobilisation of wildlife animals. The
      enzyme hyaluronidase shall improve the distribution of the intramuscularly or
      subcutaneously administered compounds in the tissue and enhance their absorption.
      These enhancing effects of two hyaluronate lyases of bacterial origin
      (Streptococcus agalactiae and Streptococcus equisimilis) and a testicular
      hyaluronidase were compared in an in vitro test. Using the isolated perfused
      bovine udder, 2 ml of a solution were administered subcutaneously containing 125
      mg/ml xylazine and 100 mg/ml ketamine and one of the above mentioned enzymes (150
      I.U.). All three enzymes enhanced the absorption rate of xylazine and ketamine
      determined by measurement of the concentration in the perfusate. The bacterial
      hyaluronate lyases were significantly more efficient, especially during the
      clinically important first minutes after administration.

PMID- 16892707
TI  - [Influence of milking technique, milking hygiene and environmental hygiene
      parameters on the microbial contamination of milking machines].
AB  - It was the aim of this study to investigate the effect of various factors of the
      milking technique, milking hygiene and environment on microbial contamination of
      the milking machine. In 31 dairy herds, the degree of bacterial contamination was
      examined by taking swabs at four locations (teat cup liner, claw, short and long
      milk tube) before the milking procedure was started using a standardized protocol
      (DIN ISO 6887-1:1999). Furthermore, the total germ count was determined in the
      first milk entering the bulk tank as well as in the bulk tank milk following
      milking. For each farm, the quality of the milking process and the condition of
      the milking machine as well as of various environmental factors were recorded. A
      subjective evaluation of the status of the milking cluster or other parts of the
      milking machine ("good" or "moderate-poor") gave more information about bacterial
      contamination than the determination of age and type of material used. A
      temperature of the rinsing water of < 42 degrees C increased the contamination
      with Pseudomonas spp. and coliform bacteria. Milking clusters kept out of the
      cluster pick-up between milking had a higher risk of microbial contamination.
      Various methods of teat cleaning before milking or of postmilking teat
      disinfection did not affect the contamination of the milking machine and the bulk
      tank milk with environmental bacteria. Furthermore, type of bedding material
      affected bacterial contamination of milking clusters and bulk tank milk. In
      conclusion, our results suggest that the microbial contamination of the milking
      machine is not only influenced by the sanitation pro-

PMID- 16892709
TI  - Retirement planning when will you be able to afford to stop working?

PMID- 16892708
TI  - [Case report: Ectopia cordis in a German Holstein calf].
AB  - A case of ectopia cordis pectoralis was diagnosed in a black and white coloured
      German Holstein calf. The heart and pericard were displaced through a fissure in
      the breastbone. The heart was connected with the thoracic cavity by its large
      vessels. Besides of the ectopia cordis no other defects of the heart were
      noticed. The liver was deformed and many organs showed passive hyperaemia. The
      calf was well developed and died under birth. The lungs were not ventilated. The
      malformed calf was inbred on a bull used for artificial insemination with an
      inbreeding coefficient of 3.125%. The ectopia cordis probably resulted from the
      fissure of the breastbone.

PMID- 16892710
TI  - The amalgam debate.

PMID- 16892711
TI  - A year of significant change for Profmed.

PMID- 16892713
TI  - A critical evaluation of the committee of preliminary inquiry of the Health
      Professions Council of South Africa, with specific reference to maxillo-facial
      and oral surgery (part 2).

PMID- 16892714
TI  - Comparative permeability of fresh and frozen/thawed porcine buccal mucosa towards
      various chemical markers.
AB  - Sometimes it is not feasible or convenient to use tissue samples immediately and
      they are then stored at -85 degrees C after being snap-frozen in liquid N2.
      Previous studies have shown that, although snap-freezing in liquid N2 does not
      alter the permeability properties of human buccal and vaginal mucosae towards
      various markers significantly, some tissue damage does occur. Slight increases in
      the permeability properties of the frozen/thawed human buccal mucosa towards
      markers were found, although these were not statistically significant. The damage
      does, however, not seem to affect the lipid permeability barrier to a meaningful
      extent. Because porcine buccal mucosa is a popular choice as a substitute for
      human buccal mucosa in many permeability studies, it was decided to evaluate the
      effect that snap-freezing, storage and thawing would have on the permeability of
      this mucosa when compared to human mucosae. Fresh and frozen/thawed buccal mucosa
      specimens were collected from freshly slaughtered pigs and permeability
      experiments at 20 degrees C and 1.5 ml/h, over a 24 hour time period, performed
      using a flow-through diffusion apparatus. The permeants tested were water,
      arecoline, vasopressin and 17beta-estradiol. Statistically significant
      differences were obtained between the flux values at steady state for water,
      arecoline and vasopressin through fresh and frozen/thawed porcine buccal mucosa.
      The estimated mean steady state flux values for 17beta-estradiol showed no
      statistically significant differences between the fresh appear to indicate that
      the lipid barrier of porcine buccal mucosa is not as resistant to snap-freezing,
      storage and thawing procedures as that of human mucosal tissue.

PMID- 16892716
TI  - A review of gagging problems in dentistry: aetiology and classification.
AB  - Some people have a pronounced gag reflex that can be a severe limitation to their
      ability to accept dental care and the clinician's ability to provide it. It can
      compromise all aspects of dentistry, from diagnostic procedures to active
      treatment and can be distressing for all concerned. Many techniques have been
      described that attempt to overcome the problem. Dentists will undoubtedly see
      patients with gagging problems and knowledge of a variety of management
      strategies is necessary to aid the delivery of dental care. This first paper
      looks at the background to gagging problems and their classification and
      categorization prior to clinical treatment. The second article will look at the
      clinical assessment of the patient presenting for dental treatment with a history
      of gagging problems. It will also review methods used to manage patients with
      gagging reflexes during dental treatment.

PMID- 16892715
TI  - Why and what type of vasoconstrictors are added to local anaesthetic solutions?

PMID- 16892717
TI  - Retrievability of the implant superstructure (part 1).

PMID- 16892718
TI  - General practitioner's radiology case 42. Qnkylosis of a tooth.

PMID- 16892719
TI  - What is your interpretation of the lesion? Noma.

PMID- 16892721
TI  - Worth repeating.

PMID- 16892720
TI  - Sedation corner 10.

PMID- 16892722
TI  - Geriatric assessment.

PMID- 16892723
TI  - Biocompatible and biodegradable phosphorylcholine ionomers with reduced protein
      adsorption and cell adhesion.
AB  - In this paper a recently developed biodegradable phosphorylcholine ionomer (PC
      ionomer) was evaluated in different biological environments with a focus on the
      adsorption of proteins (fibrinogen) and the adhesion of cells. Our results have
      shown that the polar phosphoryl choline (PC) group may be enriched at the surface
      of cast films with an added hydrophilic environment. X-ray photoelectron
      spectroscopy confirmed the surface depletion of PC groups in dry conditions, as
      nitrogen and phosphorous atoms were found in the bulk of the material but not at
      the outermost surface layer. The surface enrichment leads to a strongly
      hydrophilic surface that prevents the adsorption of proteins and reduces the
      adhesion of cells. The non-functional and hydrophobic reference poly(trimethylene
      carbonate) (PTMC) adsorbs both proteins and cells, thus the wetting and low
      adhesion behavior of the PC ionomer can be attributed to the introduced PC
      functionality. Since the in vivo acceptance of biomaterials is determined by
      their ability to withstand protein adsorption the PC ionomer described in this
      paper is highly interesting for a number of in vivo applications in which the
      adsorption of proteins may be critical, for example, blood contact events.

PMID- 16892724
TI  - Effects of hydrolysis on a new biodegradable co-polymer.
AB  - The aim of this study was to examine the feasibility of using a new low-modulus
      biodegradable thermoplastic elastomer for in vivo application as a stent cover.
      The new polymer, a thermoplastic elastomer, consists of a three-armed co-polymer
      of poly(lactide)acid (PLLA), poly(trimethylene carbonate) (PTMC) and
      poly(caprolactone) (PCL). A degradation study was performed in a buffer solution
      at 37 degrees C for 4 and 6 weeks. The effect of degradation on mechanical
      properties was studied by stress-strain measurements and explained by using
      modulated DSC, GPC and mass measurements. A tapered block of PLLA and
      trimethylene carbonate connecting the crystalline outer part and the inner
      elastic part was highly susceptible to hydrolysis and caused rapid degradation
      and subsequent loss of mechanical properties. Random chain scission and
      homogenous hydrolysis resulted in a loss in mass and molecular weight. After 6
      weeks of in vitro hydrolysis the molecular weight had decreased 54% and the
      elongation-at-break dropped from more than 300% to 90%. A medium free cell
      seeding study showed that endothelial cells adhered well to the polymeric
      material. An indicative animal study with the polymer acting as a stent cover
      showed very low levels of inflammation; however, pronounced neointima thickening
      was observed which was probably due to the premature failure of the material.

PMID- 16892726
TI  - In vitro transfection of plasmid DNA by cationized gelatin prepared from
      different amine compounds.
AB  - The objective of this paper is to compare the in vitro transfection efficiency of
      a luciferase plasmid DNA using cationized gelatin prepared from different amine
      compounds. The compounds used here were ethylenediamine, putrescine, spermidine
      and spermine, chemically introduced to the carboxyl group of gelatin for the
      cationization. Complexation of the cationized gelatin with the plasmid DNA was
      performed by simply mixing the two materials at various N+/P- mixing ratios (the
      molar number ratio of amino groups of gelatin to the phosphate groups of DNA) in
      aqueous solution. Gel retardation studies revealed that the formation of
      cationized-gelatin-plasmid DNA complexes depended on the N+/P- mixing ratio. The
      stronger interaction of plasmid DNA with the cationized gelatin of spermine
      compared to the other cationized gelatins was observed by an ethidium bromide
      intercalation assay and Scatchard binding analysis. When the transfection
      efficiency of plasmid DNA complexed with the various cationized gelatins at
      different N+/P- mixing ratios was evaluated for mouse L929 fibroblasts, the
      highest transfection efficiency was observed for the complex prepared from the
      cationized gelatin of spermine at a N+/P- mixing ratio of 2. The present study
      indicates that there is an optimal N+/P- mixing ratio and a type of amine
      compound or cationization extent of cationized gelatin to enhance the
      transfection efficiency of plasmid DNA.

PMID- 16892725
TI  - Preparation of PVA/PEI ultra-fine fibers and their composite membrane with PLA by
      electrospinning.
AB  - Ultra-fine fibers of poly(vinyl alcohol)/polyethylenimine (PVA/PEI) were prepared
      by electrospinning of their blend solutions in water. Effects of PVA/PEI mass
      ratio and the polymer concentration on the fiber morphology were discussed by
      analysis of scanning electron micrographs. Results showed that uniform ultra-fine
      fibers could be obtained from an 8% PVA/PEI solution with 75:25 mass ratio. It
      was supposed that the introduction of PVA could promote electrospinning of PEI by
      weakening the intermolecular interaction and increasing solution viscosity. A
      composite membrane of PVA/PEI with poly(D,L-lactide) (PLA) was produced by co
      electrospinning simultaneously from the aqueous 8% PVA/PEI (75:25) solution and a
      20% PLA solution in N,N-dimethylformamide in two separated syringes. Fourier
      transform infrared spectroscopy, X-ray diffraction and X-ray photoelectron
      spectroscopy verified the existence of PVA/PEI and PLA in the fibrous membrane.
      We attempted to incorporate PEI with PLA as ultra-fine fibers to diminish the
      acidic inflammation caused by biodegradation of PLA. The fibrous composite
      membrane of PVA/PEI-PLA could provide better biocompatibility and would be used
      as drug-delivery carriers or tissue-engineering scaffolds.

PMID- 16892727
TI  - Cell growth on tissue-engineering scaffolds prepared by gamma irradiation
      grafting of N-vinyl-2-pyrrolidone onto polyvinyl alcohol.
AB  - In the field of tissue engineering, promoting cell attachment and proliferation
      in polymer matrices is an attractive challenge for treating patients suffering
      from the loss or dysfunction of tissues or organs. In this study we have
      investigated the effect of grafting N-vinyl-2-pyrrolidone (NVP) by gamma
      irradiation onto polyvinyl alcohol (PVA), a highly hydrophilic and non-toxic
      material. PVA scaffolds were prepared by freeze-thaw and progen (glycerol)
      methods. In the first method, samples were freeze-thawed for three consecutive
      cycles at -25 degrees C (90 min) and room temperature (60 min); in the latter, 0
      40% glycerol was used as progen. Gamma irradiation of the scaffolds in the
      presence of NVP was performed at different concentrations (2, 3, 4 and 6%) with
      5, 10 and 15 kGy 60Co. The highest percentage of grafting was obtained at 4% NVP
      solution and 15 kGy. Cell attachment was optimal for the scaffolds prepared using
      freeze-thaw and glycerol methods with 3.8% and 2.7% polyvinyl pyrrolidone (PVP),
      respectively.

PMID- 16892728
TI  - The inflammatory cell influx and cytokines changes during transition from acute
      inflammation to fibrous repair around implanted materials.
AB  - The inflammatory and fibrous responses in a subcutaneous rat model were evaluated
      around degradable polyurethane urea (PUUR; Artelon), with titanium and tissue
      culture polystyrene (PS) discs having different surface chemical properties but
      similar surface topography. Cytokines, viability, cellular response,
      differentiation of cells and fibrous capsule formation and vascularization was
      investigated after 1, 7 and 21 days of implantation. The exudates retrieved from
      the pockets were analysed with respect to the total cell numbers, the proportions
      of cell types, the differentiation of monocytes/macrophages (ED1, ED2), the DNA
      content and the viability (LD, Trypan blue). Tumour necrosis factor alpha ((h)TNF
      alpha) and interleukin-10 ((h)IL-10) were quantified by ELISA. The number of
      blood vessels, blood vessel luminal area, blood vessel distribution and the
      fibrous capsule thickness were analysed. The highest number of cells in the
      exudates around all implants was detected during the early phase of healing (1-7
      days). The proportion of ED2-positive cells in the exudates increased from 2-8%
      at 1 day to 43-56% at 21 days. The levels of TNF-alpha were low with a decrease
      at 7 days. After 21 days high amounts of IL-10 in the exudates were detected, in
      particular around PUUR. This study shows that the transition from inflammation to
      repair (1-21 days) around PUUR, Ti and PS materials was characterized by a
      decrease in inflammatory cell influx, an increasing proportion of ED2-expressing
      macrophages, a biphasic TNF-alpha secretion, an increase of IL-10 and a fibrous
      capsule formation similar to all materials tested.

PMID- 16892730
TI  - Effect of co-solvents on the characteristics of enkephalin microcapsules.
AB  - The objective of this project was to study the effect of the presence of co
      solvents with dichloromethane on the properties of leu-enkephalin microcapsules.
      Six co-solvents, including ethyl acetate, methanol, ethanol, acetone, isopropanol
      and acetonitrile, at three concentrations of 5%, 10% and 20% (v/v), respectively,
      of dichloromethane were selected for this study. The resulting microcapsules were
      evaluated for morphology and particle size, surface area, thermal characteristics
      and efficiency of encapsulation. The analysis of particle size distribution
      showed bi- and tri-modal distribution of the microcapsules. The median particle
      size of the microcapsules was between 17 microm and 57 microm. All microcapsules
      were smaller than 90 microm. Approximately 10% of the microcapsules were smaller
      than 500 nm. In general, the microcapsules prepared with co-solvents showed
      relatively smaller median size. The microcapsules were spherical in shape. DSC
      analysis of the microcapsules showed that there were no significant differences
      in the glass transition temperatures. There were significant changes in the
      efficiency of encapsulation due to the addition of co-solvents. Substitution with
      20% methanol resulted in 40% increase in the efficiency of encapsulation (12% vs.
      17%). Furthermore, substitution with 20% ethyl acetate, isopropanol, or
      acetonitrile, reduced the efficiency of encapsulation to as low as 6%.

PMID- 16892729
TI  - Physicochemical and antimicrobial properties of boron-complexed polyglycerol
      chitosan dendrimers.
AB  - A polyglycerol with dendritic structure (PGLD) was synthesized by ring-opening
      polymerization of deprotonated glycidol using a polyglycerol as core
      functionality in a step-growth process. Then, PGLD reacted with O
      carboxymethylated chitosan to obtain PGLD-chitosan dendrimer (PGLD-Ch). After the
      reaction of PGLD-Ch with boric acid, there was a marked increase in the bulk
      viscosity evidencing physically that boron can initiate a charge transfer complex
      formation, (PGLD-Ch)B. Gel permeation chromatography analysis was used to
      characterize the molecular weight and the polydispersivity of the synthesized
      PGLD-Ch. A dendritic structure with a molecular mass of 16.7 kDa and a narrow
      polydispersity (Mw/Mn = 1.05) was obtained. 1H-NMR and 13C-NMR measurements were
      employed to assess the degree of branching in PGLD. The obtained value of 0.85
      indicates the tendency toward a dentritic structure for PGLD. The glass
      transition temperature values of (PGLD-Ch)B membranes containing 10% and 30% PGLD
      were -19 degrees C and -26 degrees C, respectively, which favor its potential use
      as surface coating of several polymers. The in vitro cytotoxicity was evaluated
      using the minimum essential medium elution test assay. Extracts of boron
      complexed PGLD exhibited lower cytotoxicity than the controls, suggesting that
      the material has an improved biocompatibility. Antibacterial studies of (PGLD
      Ch)B against Staphylococcus aureus and Pseudomonas aeruginosa showed a
      significant activity. Our study confirms and supports the effectiveness of (PGLD
      Ch)B as an antimicrobial coating due to its capacity in suppressing the bacterial
      proliferation. The best in vivo response was found for (PGLD-Ch)B-30 membranes,
      which exhibited higher synthesis of collagen fibers than PGLD-ChB-10.

PMID- 16892731
TI  - Air pollution and bronchial asthma.

PMID- 16892732
TI  - Comparison of a short course of prednisolone with sustained-release theophylline
      in the control of nocturnal asthma.
AB  - Nocturnal asthma is now considered to be a manifestation of increased bronchial
      inflammation and responsiveness at night. Inhaled steroids have been shown to be
      effective in its control. However, the role of oral steroids has not been
      defined. A double blind, randomised, parallel-group, double-dummy study was
      carried out to evaluate the role of oral prednisolone in the management of
      nocturnal asthma and compare it with the more often used sustained-release
      theophylline. Twenty chronic perennial asthmatics with complaints of at least 3
      awakenings at night due to asthmatic symptoms during the preceding week were
      included in the study and divided randomly into two groups of 10 each. Group A
      patients were put on a single, morning (8 AM) 30mg (6 x 5mg) dose of prednisolone
      plus placebo tablets b.i.d. (10 AM & 10 PM) while Group B patients received
      sustained-release theophylline (600-800mg per day) in b.i.d. dosage (10 AM & 10
      PM) plus 6 placebo tablets in the morning (8 AM). The treatments were continued
      for 1 week. The evaluation parameters included nocturnal awakenings, additional
      inhalations of salbutamol, daytime asthma scores and spirometry. Both the
      treatments effectively controlled nocturnal asthma. However, relief was quicker
      in Group A and associated with a better daytime control and a greater improvement
      in lung function. In Group A, the mean daily nocturnal asthma score fell from
      0.58 +/- 0.14 during the pretreatment week (run-in) to 0.10 +/- 0.09 during the
      treatment (P<0.001), the additional drugs score fell from 1.34 +/- 0.42 to 0.16
      +/- 0.13 (P<0.001), FVC increased from 75.3 +/- 19.4 to 83.9 +/- 12.5% predicted
      (P<0.002) and FEV1 increased from 41 +/- 10.7 to 63.7 +/- 14.3% predicted
      (P<0.001). In Group B, the mean nocturnal asthma score fell from 0.63 +/- .0.19
      to 0.26 +/- 0.15 (P<0.001) and the additional drugs score fell from 1.34 +/- 0.44
      to 0.44 +/- 0.28 (P<0.001). The increase in FVC from 73.9 +/- 18.9 to 74.9 +/-
      14.2% predicted was not significant (P>0.05) while the FEV1 increased from 39.8
      +/- 9.4 to 48.2 +/- 8.04% predicted (P<0.001). The mean daily daytime asthma
      score in Group A during the treatment was 0.41 +/- 0.17 which was significantly
      (P<0.001) lower than in Group B where it was 1.41 +/- 0.34. It was concluded that
      while both the drugs are effective, a short course of a moderately high dose of
      oral prednisolone is superior to sustained-release theophylline in controlling
      nocturnal asthma.

PMID- 16892733
TI  - Etoposide (VP-16) containing combination chemotherapy for treatment of patients
      with small cell lung cancer.
AB  - A combination chemotherapy consisting of VP-16, vincristine, cyclophosphamide and
      CCNU was used to treat 24 patients of small cell lung cancer (extensive stage
      disease - 15 and limited stage - 9). In addition, radiotherapy of 1000 to 4000
      cGys was given to primary disease in chest in 16 patients. The overall response
      rate was 95.8% with complete response (CR) in 9 (37.5%) and partial (PR) in 14
      (58.3%) cases. The overall median survival was 24 weeks. In patients with CR, it
      was 39 weeks and in those with PR this was 22.5 weeks. The lone non-responder
      survived for only 8 weeks. The drugs were well tolerated.

PMID- 16892734
TI  - Factors influencing the initiation, continuation and cessation of smoking.
AB  - Smoking is complexely related to various aspects of life style. A survey
      conducted among 573 teachers of Lucknow University to identify the various
      factors influencing the smoking habit revealed that friends played a significant
      role in initiation of smoking and its continuation. Significantly higher
      proportion of current smokers used only filter cigarettes. Majority of ex-smokers
      were successfully able to stop smoking in the first attempt, the most common
      reason for them to stop being health related. Compared to this, almost half of
      the current smokers stated that they were never advised to stop smoking by anyone
      and they had never made an attempt to quit. The results suggest that creating an
      awareness among smokers about the health hazards may encourage them to stop
      smoking.

PMID- 16892735
TI  - Unilateral hypertransradiancy in a child with recurrent chest infections.
AB  - A 3-year-old female child was treated for six recurrent episodes of cough, high
      grade fever and breathlessness during past one year. Every time total leucocyte
      counts used to range between 17,000 - 25,000 per mm3 with neutrophils over 80%.
      Except for diminished breath sounds in left basal region, systemic and chest
      examinations were normal. Her chest roentgenogram is shown in figure 1. A good
      quality chest roentgenogram could not be done because of persistent movements of
      the child.

PMID- 16892736
TI  - Acute myocardial infarction: A complication of left atrial myxoma.
AB  - A 58-year-old female patient, immediately after an acute myocardial infarction
      underwent an echocardiographic examination and emergency coronary arteriography
      which led to the discovery of left atrial infarction. Successful emergency
      coronary arterial by-pass graft (CABG) and excision of the myxoma was done within
      24 h of the onset.

PMID- 16892737
TI  - Worsening of steroid dependent asthma : A possible role of rifampicin.
AB  - A 40-year-old male patient with chronic steroid dependent asthma developed
      pulmonary tuberculosis. After administration of antituberculosis therapy with
      rifampicin, isoniazid and pyrazinamide his asthma worsened. Omission of
      rifampicin from the drug regimen successfully controlled bronchospasm.

PMID- 16892738
TI  - Bilateral morgagni hernia masquerading as mediastinal mass.
AB  - Bilateral Morgagni hernia is a rare entity. A patient of bilateral Morgagni
      hernia presenting as mediastinal mass is being reported. The hernial contents
      included transverse colon so the diagnosis could be confirmed preoperatively by
      barium enema. Surgery was curative.

PMID- 16892739
TI  - Myelomatous pleural effusion.
AB  - Pleural effusion due to myelomatous involvement is rare. We are describing such a
      case who also had soft tissue extension from iliac bone with congestive heart
      failure.

PMID- 16892741
TI  - Cough variant asthma: a frequently overlooked clinical entity.

PMID- 16892740
TI  - Generalised muscle cramps with inhalation of salmeterol.

PMID- 16892743
TI  - A clinico-radiological review of 62 cases of tropical eosinophilia in Punjab.
AB  - A clinico-radiological account of 62 cases of tropical pulmonary eosinophilia
      (TPE) seen during past seven years among permanent residents of Punjab, a non
      filarial endemic state, has been presented. In comparison to reports from
      filarial states, rhonchi (32.2%), systemic involvement (1.6%) and mottled
      radiological appearance (8%) was seen less commonly. Possible means of
      transmission have been discussed. This report should dispel the commonly held
      view that TPE is prevalent in filarial endemic regions only.

PMID- 16892742
TI  - Comparison between serum and urinary sulphadimidine acetylation as predictors of
      isoniazid acetylator status in patients with pulmonary tuberculosis.
AB  - The acetylator status of 200 pulmonary tuberculosis patients was determined by
      sulphadimidine (SDM) acetylation in (1) urine and (2) serum. In both estimations,
      distribution of the patients with regard to the acetylation rates was found to be
      bimodal. Based on the percent frequency distribution of acetylated SDM, the
      antimode for urine and serum was 65% for the former and 45% for the latter.
      Patients acetylating above 65% or 45% of administered SDM were taken as rapid
      acetylators, while those acetylating less, were slow acetylators. The ratio of
      slow to rapid acetylators in urine and serum was 58 : 42 and 66 : 34
      respectively. The renal clearance of acetylated fraction of SDM was considerably
      greater as compared to that of the unacetylated fraction. Agreement between the
      two methods as evaluated by the kappa statistic was 0.71. The determination of
      the acetylator status by the SDM acetylation test in the urine is simple to
      perform and has acceptable accuracy. It may be used as an acceptable substitute
      to serum for estimating the isoniazid inactivation status which is of
      considerable importance when patients are treated with daily/ intermittent/once
      weekly drug regimens for tuberculosis.

PMID- 16892744
TI  - Ultrasound guided aspiration biopsy of peripheral pulmonary lesions.
AB  - Forty-six patients with peripheral lung lesions underwent ultrasound-guided
      percutaneous needle aspiration biopsy. Aspirates were sent for cytological and/or
      microbiological examination. Confirmative diagnosis was obtained in 40 patients
      (86.9%). Twenty-eight patients had positive cytology for malignancy and 12
      patients with benign lesions had diagnosis made by cytologic and microbiologic
      examination. None of the lesions could be diagnosed by sputum cytology and
      fibreoptic bronchoscopy with biopsy or brushings. No complication was observed in
      any patient. We conclude that ultrasound guided aspiration biopsy is a useful and
      safe method for the diagnosis of peripheral pulmonary masses. The diagnostic
      yield far exceeds that which can be obtained by sputum cytology and fibreoptic
      bronchoscopy with biopsy.

PMID- 16892745
TI  - Adrenocortical reserve in patients with tuberculosis.

PMID- 16892746
TI  - Lobar atelectasis: an unusual aetiology.

PMID- 16892747
TI  - Yellow nail syndrome: a rarity in Indians?
AB  - Reports of yellow nail syndrome have been few and far between. The classical
      triad of the syndrome has not been reported in Indian literature. We report a
      case of yellow nail syndrome in a forty-year-old male, who had yellowish-brown
      nails from birth. He developed lymphoedema of the legs at the age of twenty years
      and presented with pleural effusion at the age of forty years. Although a case of
      yellow nail syndrome has been reported from India, the classical triad of the
      syndrome is yet to be documented from our country. The condition may be missed
      because of the long time difference in presentation of different components of
      the syndrome and also because of the dark skin colour of Indians.

PMID- 16892749
TI  - Herniation of lung.
AB  - Non-traumatic, acquired lung hernia of pathologic variety is rare, but can be
      associated with tuberculous rib osteitis.

PMID- 16892748
TI  - Chronic berylliosis of the lung: report of a case.
AB  - We report a case of chronic berylliosis of the lung in a patient who was exposed
      to copper beryllium alloy, which was mistaken and being treated as miliary
      tuberculosis. The relevant literature is reviewed.

PMID- 16892751
TI  - Anaesthesia in the UK--a continuum of challenges.

PMID- 16892750
TI  - Late bronchoplasty for missed traumatic rupture of bronchus.
AB  - Two patients of traumatic rupture of main bronchus are reported here. One patient
      presented 2 years after blunt chest trauma while the other patient presented 9
      weeks after trauma. Lesion in both patients were missed in the immediate post
      trauma period. In both patients pulmonary angiogram demonstrated normal
      vasculature in the atelectatic lung, while intraoperatively good compliance and
      elasticity were found. Bronchoplasty done in both patients had good postoperative
      results.

PMID- 16892752
TI  - Overview of 12 months anaesthetic activity in a UK field hospital on enduring
      operations in Iraq.
AB  - The British Field Hospital facility in Southern Iraq has seen a continuous
      turnover of patient admissions since the start of offensive operations during the
      2003 Gulf conflict (Operation TELIC). During the war a number of procedures were
      carried out and these have been well described to date. On May 1st 2003 President
      Bush declared an end to high intensity operations with a subsequent reduction in
      medical activity. However, the facility has continued to provide medical care to
      large numbers of service and civilian patients from the end of hostilities to the
      present day. The purpose of this review is to present anaesthetic and demographic
      data relating to procedures carried out at the Field Hospital over a 12-month
      period from the end of the war-fighting phase of the conflict.

PMID- 16892753
TI  - Battlefield trauma and pain.

PMID- 16892754
TI  - Postoperative vigilance in patients with total intravenous anaesthesia with
      ketamine/propofol.
AB  - Ketamine is a strong acting analgesic drug, used mainly in trauma and emergency
      medicine settings, as well as for minor procedures. Its pharmacological
      properties make it a useful drug for military anaesthesia. Ketamine acts by
      blocking activation of the spinal and supraspinal NMDA-type glutamate and opioid
      receptors. It produces dissociative anaesthesia, which means that patients might
      remain conscious, though insensitive to pain and amnesic (anterograde). Dysphoria
      and hallucinations are the main side effects in the early recovery period. We
      studied the incidence of post operative nausea and vomiting, vigilance
      disturbances and haemodynamic instability during combined ketamine and propofol
      anaesthesia. No patient suffered from postoperative nausea and vomiting. No
      haemodynamic instability could be observed in any of the patients. The
      interesting point is that though there were no unpleasant emergence phenomenons,
      no patient reached the preoperative state of vigilance within two hours after
      extubation. These results indicate that for plastic/dermatological surgical
      procedures, patients undergoing ketamine/propofol anaesthesia do not require
      excessive haemodynamic monitoring, but do need prolonged personal observation in
      the postoperative period.

PMID- 16892755
TI  - Royal Navy medical officers and pre-hospital immediate medical care in Hampshire.

PMID- 16892756
TI  - A case of fatal shotgun pellet embolism.

PMID- 16892757
TI  - Bochdalek hernia in a soldier.
AB  - Congenital diaphragmatic hernias are most often seen in infants. They may rarely
      be discovered in adulthood. This case report describes the management of a
      soldier presenting with acute bowel obstruction and respiratory embarrassment in
      a military hospital. The surgical repair was achieved with a laparotomy.
      Effective epidural analgesia and early physiotherapy were axiomatic of his
      uncomplicated post-operative course.

PMID- 16892758
TI  - Cutaneous myiasis with Dermatobia hominis (human bot fly) larvae treated both
      conservatively and surgically.
AB  - A case is presented of infestation with the larvae of Dermatobia hominis (human
      bot fly). This case is unusual in that it provides an example of three different
      outcomes for separate lesions in the same patient; spontaneous resolution,
      conservative treatment and surgical intervention. It also illustrates that
      myiasis should be included in the differential diagnosis of any skin lesion of a
      patient returning from the tropics.

PMID- 16892759
TI  - The management of intraorbital foreign bodies.

PMID- 16892760
TI  - A qualification in medical education--a luxury or a necessity?
AB  - As doctors, in all spheres of medical practice, we have a responsibility to
      contribute to the education and training of other doctors, medical students and
      non-medical healthcare professionals. This is particularly pertinent in the Royal
      Naval Medical Service where effective education and training of medical teams is
      extremely important, particularly when preparing for the operational environment.
      However, it is not unusual to reach a fairly senior stage of a medical career
      without ever receiving any formal instruction in methods of teaching. So, it is
      not surprising that most people can recall being on the receiving end of a bad
      teaching experience; few doctors have escaped the familiar scenario of being
      taught by humiliation on a ward round. Accepting that good teaching abilities are
      not innate, I would suggest that we all have a professional obligation to develop
      and maintain our skills in the field of medical education. The Royal College of
      Anaesthetists have formalised this obligation by including the subject of medical
      education in the curriculum for Specialist Registrar training. There is a wealth
      of courses, which are easily accessed and which offer a broad introduction to
      generic teaching methods. In addition, many universities now offer part-time and
      distance-learning courses that lead to a qualification in education, specific to
      medical practice. Hopefully, this account has given an overview of the available
      resources and has provided food for thought for anyone wishing to develop an
      interest in medical education.

PMID- 16892761
TI  - The Haywood Club Tri-Service Medical Society.

PMID- 16892762
TI  - Moving research into the community: learning by experience.

PMID- 16892763
TI  - From research to reality: from the National Cooperative Inner-City Asthma Study
      to the inner-city asthma implementation.
AB  - Several themes emerged from the information provided in this supplement. 1.
      Implementation of the protocol was feasible, although retention of participants
      was challenging and customization at each site was essential. 2. Master's degree
      level social workers were well suited to partnering with health care
      professionals to address the many issues involved in caring for children with
      asthma and their families. 3. Collaboration between team members and community
      partners was critical to successful implementation. 4. Sustainability beyond
      external funding is attainable if local funding is sought and outcome measures
      that are considered important to the community are measured and reported.

PMID- 16892764
TI  - The Inner-City Asthma Intervention: description of a community-based
      implementation of an evidence-based approach to asthma management.
AB  - BACKGROUND: In 2000, the Centers for Disease Control and Prevention funded a 4
      year project to implement the Inner-City Asthma Intervention (ICAI)-an asthma
      treatment and management project based on the protocol developed for the National
      Cooperative Inner-City Asthma Study (NCICAS) funded by the National Institutes of
      Health, National Institute of Allergy and Infectious Disease. OBJECTIVE: To
      describe the ICAI's major components and implementation issues. METHODS:
      Information contained in this article is based on project activity and management
      reports, site client tracking and data collection reports, site visit and other
      program oversight activity, and general subject matter knowledge. The site client
      tracking data collection process varied among sites during the intervention.
      Common definitions and processes were developed and implemented as needed.
      RESULTS: Three of the 24 original sites discontinued participation. The remaining
      sites enrolled 4,174 children into the intervention. Although the project ended
      earlier than originally scheduled, 1,035 children completed the entire
      intervention. Of the 3,139 children who did not complete the entire protocol,
      1,355 children and their families completed the core activities or the core
      activities plus one or more follow-up activities. CONCLUSION: The ICAI project
      demonstrated that although there were a number of implementation issues to
      overcome, it is possible to implement effectively a proven National Institutes of
      Health protocol in the community setting.

PMID- 16892765
TI  - Asthma risk factor assessment: what are the needs of inner-city families?
AB  - BACKGROUND: A complex array of risk factors contributes to sustained high levels
      of asthma morbidity in inner-city children. OBJECTIVE: To describe risk factors
      for asthma morbidity in a national sample of inner-city children with persistent
      asthma. METHODS: This study examined baseline questionnaire results from 1,772
      children ages 5 to 11 years old with moderate to severe persistent asthma who
      enrolled in the Centers for Disease Control and Prevention-funded Inner-City
      Asthma Intervention between April 2001 and March 2004. Risk for asthma morbidity
      was assessed in 9 domains using the Child Asthma Risk Assessment Tool. The
      domains included environmental exposures, parental stress, medication adherence,
      pessimistic asthma beliefs, smoke exposure, aeroallergen exposure, child
      psychological well-being, responsibility for medication administration, and
      medical care. RESULTS: A total of 51% of families demonstrated high risk of
      asthma morbidity in 3 or more domains. High risk of asthma morbidity was
      suggested based on household environmental exposures (47.7%), high parental
      stress (38.5%), poor medication adherence (38.3%), pessimistic asthma beliefs
      (31.8%), environmental tobacco smoke (24.4%), sensitization to aeroallergens in
      the home (24.8%), child behavioral or emotional concerns (22.9%), child assigned
      responsibility for medication administration (21.2%), and poor medical care
      (20.7%). Allergy testing was completed for 40% of the participating children. Of
      these children, 61% were exposed to aeroallergens in their home to which they
      were sensitized. CONCLUSIONS: In this national sample of inner-city children,
      multiple risk factors for asthma morbidity were identified. Asthma programs that
      provide multilevel support and intervention are needed to reduce the burden of
      asthma on inner-city families.

PMID- 16892766
TI  - The Inner-City Asthma Intervention asthma counselor program: a collaborative
      model between physician and social worker to help empower families.
AB  - BACKGROUND: The Inner-City Asthma Intervention (ICAI) asthma counselor program
      was modeled after interventions proven to be effective by the National
      Cooperative Inner-City Asthma Study (NCICAS) with inner-city children with
      asthma. The objective of the ICAI program was to translate and implement the
      NCICAS intervention into the real-world setting. OBJECTIVE: To describe the
      unique pairing of a master's degree-level social worker asthma counselor (AC) and
      physician program manager (PM) as they collaborate to implement a successful
      chronic disease intervention program. METHODS: A case-study design was used to
      describe the asthma counselor program collaboration at our site. This information
      was supplemented by additional qualitative data from the final report submitted
      by the Alliance of Community Health Plans to the Centers for Disease Control and
      Prevention and from questionnaire data and enrollment and retention data compiled
      by Wood et al. RESULTS: A master's degree level trained social worker functioned
      as an AC and successfully collaborated with a physician PM to help combat one of
      the most common chronic diseases of childhood. This is evident when evaluating
      administration, recruitment, education and system issues, and community outreach.
      CONCLUSIONS: The AC/PM partnership is a blueprint of how a successful
      collaboration may be duplicated by future social worker-physician teams. An
      effective program needs to address administrative issues, patient recruitment,
      ongoing team education, patient retention, and community outreach. Practical
      examples of each element are described.

PMID- 16892767
TI  - Implementation of an asthma intervention in the inner city.
AB  - BACKGROUND: Despite availability of asthma self-management interventions for
      children, few have been implemented in community-based settings. OBJECTIVE: To
      describe implementation of the Inner-City Asthma Intervention and factors
      associated with higher rates of program completion by enrollees. METHODS:
      Descriptive analyses of data from multiple data sources. Two-tailed Pearson
      correlation coefficients and analyses of variance were used to calculate
      associations of descriptive variables with the retention rate (percentage of
      enrolled children who completed the core intervention and had more than 1 follow
      up visit) and with the percentage who had allergy testing done. RESULTS: A total
      of 4,174 children were enrolled at 22 sites; 2,153 (52%) completed the core
      intervention and had more than 1 follow-up visit. A total of 2,014 enrolled
      children (48%) were tested for allergies. Retention was related to type and
      location of site, ease of obtaining written plans, language and ethnicity of
      asthma counselor, and on-site allergy testing. Higher rates of allergy testing
      were associated with the same factors, as well as flexibility in scheduling and
      selective enrollment of participants. CONCLUSIONS: Inner-city children with
      asthma can be enrolled in the Inner-City Asthma Intervention outside a controlled
      research setting. However, completion of all intervention components is difficult
      to achieve. We identify having an asthma counselor who is representative of the
      community, access to asthma action plans, and on-site allergy testing as factors
      that facilitate the implementation of this intervention in community-based
      settings.

PMID- 16892768
TI  - Utilization patterns in an asthma intervention.
AB  - BACKGROUND: The National Cooperative Inner-City Asthma Study (NCICAS) tested a
      model of asthma management in which a master's degree-prepared social worker
      functioned as an asthma counselor. The NCICAS resulted in decreased symptom days
      and a trend toward fewer emergency department (ED) visits and hospital admissions
      in the intervention group compared with the control group. OBJECTIVE: To
      determine whether a real-world implementation would give similar results to the
      NCICAS. METHODS: Children with moderate or severe persistent asthma were enrolled
      in a 1-year program, the Inner-City Asthma Intervention (ICAI) program, modeled
      on the NCICAS. Since the program initially was not designed to be research, data
      were collected retrospectively. ED and hospital visits were compared 1 year
      before and after the intervention at 2 of the intervention sites, Children's
      Mercy Hospital (CMH) and Baystate Medical Center, to determine whether there was
      a significant change. RESULTS: Data for 93 children from CMH and 77 from Baystate
      were evaluated. At CMH annual ED visits were 0.38 before, 0.42 during, and 0.41
      after the intervention, whereas at Baystate ED visits were 0.09 before, 0.17
      during, and 0.15 after the intervention. Mean hospitalizations at CMH increased
      from 0.06 before to 0.22 during and then decreased to 0.12 after (P > .05),
      whereas admissions at Baystate increased from 0.03 before to 0.05 during and 0.04
      after the intervention. CONCLUSIONS: Asthma self-management interventions can
      lead to decreases in asthma utilization under controlled circumstances. Further
      prospective studies are needed to determinewhether the ICAI intervention is
      effective under real-world conditions.

PMID- 16892769
TI  - An analysis of predictors of sustainability efforts at the Inner-City Asthma
      Intervention sites: after the funding is gone.
AB  - BACKGROUND: The Inner-City Asthma Intervention was a national, multicenter
      implementation of an evidence-based intervention to reduce asthma morbidity in
      inner-city children that was funded by the Centers for Disease Control and
      Prevention. Funding was initially planned for 4 years beginning in April 2001,
      but because of budgetary changes funding ceased in September 2004, 6 months
      before the original plan. Some sites were able to sustain their asthma program
      when the funding ended and others were not. OBJECTIVE: To compare characteristics
      of sites that were able to sustain their asthma program after the original
      funding ended with those that were not. METHODS: Data were collected from the
      project manager at each site in an electronic survey and through telephone
      interview in November 2003 and August 2005. Using contingency tables, we examined
      the bivariate relationship between each proposed factor and our outcome measure,
      secured funding. RESULTS: Of the 18 sites that completed the survey, 50% reported
      continued funding. All sustainable sites received funding from multiple sources,
      including either the hospital or the community. One site received federal funding
      and one site received state funding. Of the sites that presented data to multiple
      funders, 6 of 9 were sustained (P = .05). CONCLUSIONS: Sustainable programs were
      more likely to be funded locally. Programs that used an evaluative process,
      including patient outcomes data, to demonstrate the importance of the program to
      their institution and community were more likely to obtain continued funding
      compared with those that did not.

PMID- 16892771
TI  - Sunflower.

PMID- 16892770
TI  - The Inner-City Asthma Intervention tool kit: best practices and lessons learned.
AB  - BACKGROUND: Asthma is a major public health problem of increasing concern in the
      United States. Low-income populations, minorities, and children living in inner
      cities experience disproportionately higher morbidity and mortality due to
      asthma. In 1991, the National Institute of Allergy and Infectious Disease at the
      National Institutes of Health funded the National Cooperative Inner-City Asthma
      Study (NCICAS), the foundation for the Centers for Disease Control and Prevention
      (CDC)-funded Inner-City Asthma Intervention (ICAI) on which the tool kit
      discussed in this article is based. OBJECTIVE: To summarize the purpose and
      content of a tool kit for health care organizations that wish to enhance their
      asthma management efforts and to improve the quality of life of children with
      asthma and their families. METHODS: The ICAI was tailored to the individual child
      and family through a combination of group and individual activities (core) and
      follow-up. Information contained in the tool kit is based on project reports,
      tracking and data collection reports, program oversight activity, and general
      subject matter knowledge. RESULTS: Although the NCICAS proved successful, moving
      from a research design to the real world of implementation was difficult. The
      tool kit draws on the experience of implementation and provides strategies,
      options, and considerations for health care organizations to use in tailoring
      project activities. CONCLUSION: The ICAI demonstrated that committed health care
      organizations, with trained and experienced individuals, could help empower
      children and families to manage childhood asthma. The tool kit was designed to
      share the best practices and lessons learned from the ICAI implementation of the
      NCICAS protocol at the community level.

PMID- 16892772
TI  - Running on empty.

PMID- 16892773
TI  - Anaphylaxis: an overview from one referral clinic.

PMID- 16892774
TI  - Asthma education for the frequent emergency department visitor: does it work?

PMID- 16892775
TI  - Accidental needle stick prevention: an important, costly, unsafe policy
      revisited.

PMID- 16892777
TI  - The use of inhaled formoterol in the treatment of asthma.
AB  - OBJECTIVE: To discuss the clinical efficacy and safety of formoterol when used to
      relieve symptoms of asthma and prevent exercise-induced bronchoconstriction
      (EIB). DATA SOURCES: A PubMed search was performed for articles published between
      1997 and 2005 with the keywords formoterol, asthma, and long-acting beta2
      adrenergic agonist, with cross-referencing to identify peer-reviewed journal
      articles. STUDY SELECTION: Published articles on the clinical use of formoterol
      for asthma or EIB were included as well as articles detailing the pharmacologic
      properties of the drug. To present a thorough review of the literature, published
      studies based on patient number, study design, or other measures of study quality
      were not excluded. RESULTS: Formoterol is the only long-acting beta2-adrenergic
      agonist that combines a rapid onset of action (within 3 minutes) with a long
      duration of effect (approximately 12 hours). Clinically, as recommended by asthma
      treatment guidelines, formoterol in conjunction with inhaled corticosteroids
      (ICSs) is a preferred treatment for moderate to severe persistent asthma.
      Significant clinical data support the use of formoterol in combination with ICSs
      for the treatment of asthma, with studies demonstrating improved pulmonary
      function and symptom scores and decreased need for maintenance ICSs and short
      acting beta2-adrenergic agonists (SABAs) as relief medication. Recent studies
      also demonstrate that use of formoterol as needed as relief medication is
      associated with a prolonged time to exacerbation, improved pulmonary function,
      and decreased asthma symptoms. When used as monotherapy, formoterol provides
      protection against EIB. Clinical data also demonstrate that formoterol is safe
      and well tolerated even in high doses, with an adverse event profile similar to
      that of SABAs. CONCLUSION: Overall, formoterol is safe and effective as adjunct
      controller therapy for moderate and severe persistent asthma and as monotherapy
      for EIB.

PMID- 16892776
TI  - Food allergy and the introduction of solid foods to infants: a consensus
      document. Adverse Reactions to Foods Committee, American College of Allergy,
      Asthma and Immunology.
AB  - OBJECTIVE: To make recommendations based on a critical review of the evidence for
      the timing of the introduction of solid foods and its possible role in the
      development of food allergy. DATA SOURCES: MEDLINE searches using the following
      search algorithm: [weaning AND infant AND allergy]/[food allergy AND
      sensitization]/[dietary prevention AND food allergy OR allergens]/[Jan 1980-Feb
      2006]. STUDY SELECTION: Using the authors' clinical experience and research
      expertise, 52 studies were retrieved that satisfied the following conditions:
      English language, journal impact factor above 1 or scientific society, expert, or
      institutional publication, and appraisable using the World Health Organization
      categories of evidence. RESULTS: Available information suggests that early
      introduction can increase the risk of food allergy, that avoidance of solids can
      prevent the development of specific food allergies, that some foods are more
      allergenic than others, and that some food allergies are more persistent than
      others. CONCLUSIONS: Pediatricians and allergists should cautiously individualize
      the introduction of solids into the infants' diet. With assessed risk of allergy,
      the optimal age for the introduction of selected supplemental foods should be 6
      months, dairy products 12 months, hen's egg 24 months, and peanut, tree nuts,
      fish, and seafood at least 36 months. For all infants, complementary feeding can
      be introduced from the sixth month, and egg, peanut, tree nuts, fish, and seafood
      introduction require caution. Foods should be introduced one at a time in small
      amounts. Mixed foods containing various food allergens should not be given unless
      tolerance to every ingredient has been assessed.

PMID- 16892778
TI  - Dose counting and the use of pressurized metered-dose inhalers: running on empty.
AB  - BACKGROUND: Pressurized metered-dose inhalers (pMDIs) are the cornerstone of
      asthma treatment. The pMDI is an economic and portable medication delivery
      system, but the device does not indicate how much medicine remains in the
      canister once a patient starts using it. OBJECTIVE: To determine how patients
      evaluate the contents of their pMDI and whether they are either discarding
      inhalers when medication remains or using inhalers beyond the indicated number of
      doses. METHODS: This study was conducted in April 2003 via a 6.5-minute telephone
      interview with a random sample of 500 families with asthma from across the United
      States. RESULTS: Of the 500 respondents participating in the telephone interview,
      nearly one third (31.6%) named an inhaled corticosteroid or bronchodilator and
      inhaled corticosteroid combination as the inhaler used when wheezing, coughing,
      or short of breath. Respondents using a bronchodilator (n = 342) varied in the
      frequency with which they use their pMDIs: 31.9% daily, 18.7% weekly, 23.4%
      monthly, and 23.1% less than once per month. More than half (53.8%) of
      bronchodilator users refill their prescriptions more frequently than recommended
      by national guidelines. Only 36% of bronchodilator users reported ever having
      been told to keep track of pMDI doses used. Of those, 79% had been advised to do
      so by a physician, 6% by a pharmacist, and 3% by a nurse. Eighty-seven (25%) of
      the 342 respondents who named a bronchodilator reported having found their pMDI
      empty during an asthma exacerbation. Seven of those patients had to call 911. Of
      these 87 patients, 71 (82%) considered their pMDI empty when absolutely nothing
      came out. CONCLUSIONS: Patients do not have a reliable means of monitoring the
      contents of their metered-dose inhalers, which is causing serious problems that
      need to be addressed. Given the necessity of a reliable dose counting method, it
      is clear that manufacturers should include dose counters as a standard feature of
      every metered-dose inhaler.

PMID- 16892779
TI  - Anaphylaxis: a review of 601 cases.
AB  - BACKGROUND: The allergist usually sees patients with anaphylaxis after the event
      for the purposes of identifying the cause, establishing a prognosis, and
      preventing further episodes. Knowledge of the characteristics of such patients is
      essential to achieve these goals. OBJECTIVE: To examine the natural history,
      clinical manifestations, and factors that affect the patients' adherence to
      suggested treatment and preventive strategies of anaphylaxis. METHODS: A
      retrospective medical record review spanning 25 years (1978-2003) and follow-up
      questionnaires were used to obtain data on 601 patients who presented with
      anaphylaxis of unknown origin to a private university-affiliated allergy
      immunology practice. RESULTS: Patients ranged in age from 1 to 79 years, with a
      mean age of 37 years. Females comprised 62% of cases. Causes of anaphylaxis were
      elucidated in 41% of cases. Known causes included foods in 131 patients (22%),
      medications in 69 cases (11%), and exercise in 31 cases (5%). Two hundred twenty
      three patients (37%) were found to be atopic by history confirmed with skin prick
      testing. The most common manifestation was urticaria and/or angioedema, reported
      in 87% of patients. Systemic mastocytosis was found in 3 patients. Episodes
      tended to decline in frequency with time. Adherence to instructions to carry
      epinephrine can be improved with more effective teaching. CONCLUSIONS: In most
      cases, the cause of anaphylaxis is undetermined. Women are affected more commonly
      than men. Systemic mastocytosis should be considered in cases of idiopathic
      anaphylaxis, and patients with a history of atopy are at an increased risk of
      developing anaphylaxis. Patients are more reliably carrying epinephrine as a
      result of changes in physician instructions. Finally, anaphylactic episodes tend
      to decrease in frequency and severity with time.

PMID- 16892780
TI  - Randomized trial of a comprehensive asthma education program after an emergency
      department visit.
AB  - BACKGROUND: Patients with asthma who visit the emergency department (ED) may
      benefit from education that optimizes self-management and treatment. OBJECTIVE:
      To conduct a randomized trial of asthma education (AE) after an ED visit.
      METHODS: Patients who present with acute asthma and history consistent with
      moderate to severe persistent asthma or recent ED visits were stratified by age
      (adult, child) and randomly assigned to intervention or usual care during the ED
      visit. The intervention was conducted by trained asthma educators and included a
      facilitated office visit with the primary care physician followed by a home
      visit. Intention-to-treat analysis was conducted, with time to first asthma
      relapse (either ED or unscheduled urgent office visit) during the 6-month follow
      up period used as the primary outcome. RESULTS: Of the 239 patients analyzed, 46%
      were adults, 46% were male, 30% were African American, and 56% had moderate to
      severe persistent asthma. Follow-up information was obtained on 191 patients
      (80%) at 6 months; 23.1% of the intervention group vs 31.1% of the usual care
      group had an urgent asthma visit (hazard ratio [HR], 0.79; 95% confidence
      interval [CI], 0.48-1.29). Overall, 39% of the 117 patients assigned to the
      intervention group did not comply with any of the post-ED activities. Subgroup
      analysis suggested greater benefit among children (HR, 0.62; 95% CI, 0.33-1.19)
      than adults (HR, 1.08; 95% CI, 0.50-2.33). CONCLUSIONS: Delivery of a
      comprehensive AE program after an ED visit was ineffective in adult patients;
      however, it may be effective in children. Further research on alternative AE
      delivery strategies appears warranted to reduce the burden of asthma visits to
      the ED.

PMID- 16892781
TI  - Accidental needle sticks, the Occupational Safety and Health Administration, and
      the fallacy of public policy.
AB  - BACKGROUND: Current Occupational Safety and Health Administration (OSHA)
      guidelines mandate the use of safety needles when allergy injections are given.
      Safety needles for intradermal testing remain optional. Whether safety needles
      reduce the number of accidental needle sticks (ANSs) in the outpatient setting
      has yet to be proven. OBJECTIVE: To determine the rate of ANSs with new (safety)
      needles vs old needles used in allergy immunotherapy and intradermal testing.
      METHODS: Allergy practices from 22 states were surveyed by e-mail. RESULTS:
      Seventy practices (28%) responded to the survey. Twice as many ANSs occurred in
      practices giving immunotherapy when using new needles vs old needles (P < .01).
      The rate of ANSs was roughly the same for intradermal testing with new needles vs
      old needles. CONCLUSIONS: These findings further question whether OSHA's
      guidelines for safety needle use in outpatient practice need revision and if
      allergy practices might be excluded from the requirement to use safety needles.

PMID- 16892782
TI  - Effects of anti-inflammatory therapies on recurrent and low-grade respiratory
      syncytial virus infections in a murine model of asthma.
AB  - BACKGROUND: Recurrent and subclinical viral respiratory tract infections could
      immunologically exacerbate allergic airway inflammation. However, the most
      appropriate treatment for virus-induced asthma exacerbation is yet to be
      established. The effects of glucocorticoids in virus-induced acute asthma are
      controversial. OBJECTIVE: To determine the effects of representative anti
      inflammatory therapies for asthma--glucocorticoids and leukotriene receptor
      antagonists (LTRAs)--in mite allergen-sensitized and repeatedly low-grade
      respiratory syncytial virus (RSV)--infected mice. METHODS: Dermatophagoides
      farinae-sensitized mice were inoculated twice with low-grade RSV and
      subcutaneously injected with either a glucocorticoid or an LTRA for 4 consecutive
      days. Lung inflammation, cytokine profiles, LT production, and viral RNA in lung
      tissues were compared in 5 groups of 8 mice each: controls, D farinae allergen
      sensitized, D farinae sensitized and RSV infected, D farinae sensitized and RSV
      infected with dexamethasone, and D farinae sensitized and RSV infected with
      pranlukast, an LTRA. RESULTS: Allergic airway inflammation in D farinae mice was
      significantly enhanced by recurrent and low-grade RSV infections (RLRIs). The
      glucocorticoid attenuated allergic airway inflammation, which was associated with
      interleukin 5 (IL-5) and interferon-gamma (IFN-gamma) suppression in lung
      draining lymph nodes without affecting viral quantity. The LTRA also attenuated
      allergic airway inflammation in D farinae-RSV mice with concomitant inhibition of
      IL-5 but not IFN-gamma. Dermatophagoides farinae allergen sensitization
      significantly increased LTs in the airway, whereas RLRIs did not further enhance
      LT production. CONCLUSIONS: Glucocorticoids and LTRAs significantly inhibit RLRI
      induced exacerbation of allergic airway inflammation by distinct pathways.
      Dexamethasone suppressed nonspecific cytokines, whereas viral RNA did not
      increase via suppression of immunity. In contrast, pranlukast specifically
      inhibited IL-5 but not IFN-gamma.

PMID- 16892783
TI  - Allergenic contribution of the IgE-reactive domains of the 1,3-beta-glucanase Ole
      e 9: diagnostic value in olive pollen allergy.
AB  - BACKGROUND: Designing of methods for an accurate diagnosis is a main goal of
      allergy research. Olive pollen allergy is currently diagnosed using commercially
      available pollen extracts that do not allow identification of the molecules that
      elicit the disease. OBJECTIVE: To analyze the suitability of using the N- and C
      terminal domains (NtD and CtD, respectively) of the 1,3-beta-glucanase Ole e 9, a
      major allergen from olive pollen, for in vitro diagnosis. METHODS: Serum samples
      from 55 olive-allergic patients were assayed using enzyme-linked immunosorbent
      assay to study hypersensitive patients with IgE reactivity to Ole e 9. The
      specific IgEs to NtD and CtD, obtained by recombinant technology, were determined
      by means of immunoblotting, enzyme-linked immunosorbent assay, and inhibition
      assays. RESULTS: Thirty-one of 33 serum samples from Ole e 9-allergic patients
      were IgE reactive to recombinant NtD (rNtD) (n = 26 [79%]), recombinant CtD
      (rCtD) (n = 22 [67%]), or both (n = 17 [52%]). Nine patients (27%) were
      exclusively reactive to rNtD and 5 (15%) to rCtD. Inhibition assays of IgE
      binding to Ole e 9 with a mixture of both domains abolished 90% of the binding,
      whereas 44% and 45% were abolished when rNtD and rCtD were used, respectively.
      CONCLUSIONS: Because sensitization to NtD or CtD of Ole e 9 could be correlated
      to vegetable food-latex-pollen cross-reactivity processes or to the exacerbation
      and persistence of asthma, respectively, these molecules could be used in vitro
      as markers of disease to classify patients and to design a patient-tailored
      immunotherapy approach.

PMID- 16892784
TI  - Intercellular adhesion molecule 1 and tumor necrosis factor alpha in asthma and
      persistent allergic rhinitis: relationship with disease severity.
AB  - BACKGROUND: Tumor necrosis factor alpha (TNF-alpha) is involved in the up
      regulation of intercellular adhesion molecule 1 (ICAM-1). Allergic rhinitis is
      often associated with bronchial hyperresponsiveness. OBJECTIVE: We investigated
      the relationship between allergic airway disease severity and serum
      concentrations of soluble ICAM-1 (sICAM-1) and TNF-alpha and nasal expression of
      ICAM-1. METHODS: Serum concentrations of TNF-alpha and sICAM-1 were investigated
      in 85 adults with persistent rhinitis and 90 patients with asthma. Seventy
      patients with rhinitis were challenged with methacholine. Nasal biopsy for ICAM-1
      expression was performed in 6 patients with moderate-severe rhinitis and in 6
      patients with mild rhinitis. RESULTS: In patients with rhinitis, serum sICAM-1
      concentrations were as follows: group without bronchial hyperresponsiveness (n =
      29), 206.85 ng/mL; group with bronchial hyperresponsiveness but without asthma
      symptoms (n = 20), 233.39 ng/mL; and group with newly recognized asthma (n = 21),
      260.06 ng/mL. The sICAM-1 level was significantly lower in patients with mild
      rhinitis (216.21 ng/mL) than in patients with moderate-severe rhinitis (244.08
      ng/mL). Nasal ICAM-1 expression was significantly higher in the moderate-severe
      rhinitis group than in the mild rhinitis group. In patients with asthma, serum
      concentrations of sICAM-1 were as follows: patients with mild asthma, 272.8
      ng/mL; patients with moderate asthma, 340.16 ng/mL; patients with severe asthma
      without oral corticosteroids therapy, 426.74 ng/mL; and patients with severe
      asthma with oral corticosteroids therapy, 314 ng/mL. The serum TNF-alphaa
      concentration differed between patients with rhinitis (n = 15) (1.065 pg/mL) and
      patients with asthma (n = 12) (3.46 pg/mL). Among patients with asthma, TNF-alpha
      concentrations were similar in all groups classified according to the disease
      severity. CONCLUSIONS: sICAM and ICAM-1 expression correlates with airways
      diseases severity.

PMID- 16892785
TI  - Mixed-up nuts: identification of peanuts and tree nuts by children.
AB  - BACKGROUND: Peanuts and tree nuts frequently cause severe allergic reactions. Nut
      avoidance is the key treatment, and accurate identification of nuts is essential
      for successful avoidance. OBJECTIVES: To determine the age at which nut-allergic
      and nonallergic children can accurately identify various nuts and whether nut
      allergic children can identify nuts they should avoid. METHODS: A "nut box" was
      constructed containing samples of 11 common nuts and pine nuts. Nut-allergic and
      nonallergic children were asked to identify the nuts, and their responses were
      compared and correlated by age. Nut-allergic children were asked to identify the
      nut(s) that they should not eat. RESULTS: One hundred children (37 allergic and
      63 nonallergic) were enrolled. The mean number of nuts correctly identified was
      only 2.7 per child and increased with age, but there was large variation. Fifty
      nine children identified 2 or fewer nuts. Peanuts in the shell were identified
      most often (89% of children), followed by peanuts out of the shell (52%). Other
      nuts were identified less commonly, ranging from 32% for pistachios to 0% for
      Brazil nuts. Nut-allergic children were not better able to correctly identify
      tree nuts and were less able in the case of peanuts. Of the nut-allergic
      children, 10 (27%) could not identify the peanut or tree nut to which they were
      allergic. CONCLUSIONS: In general, children, including those who are allergic to
      nuts, can identify few nuts. This lack of recognition could put them at increased
      risk for unintentional ingestion. As part of an overall educational plan, nut
      allergic children should be taught not only to avoid but also to identify the nut
      to which they are allergic.

PMID- 16892786
TI  - Breastfeeding history and childhood allergic status in a prospective birth
      cohort.
AB  - BACKGROUND: Breastfeeding provides the best possible nutrition for newborns, but
      its role in the development of allergies is complex. OBJECTIVE: To examine the
      relationship between breastfeeding and early childhood skin sensitization.
      METHODS: In a birth cohort of 405 children from the Childhood Allergy Study, we
      used maternal report to classify children's duration of breastfeeding and whether
      they were breastfed only, formula fed only, or both. We examined the
      relationships between this information and childhood allergies as determined by
      skin prick testing for inhalant allergens at age 6 to 7 years. RESULTS: There was
      no association between duration of breastfeeding and risk of allergic
      sensitization. Overall, children who were breastfed only were 50% more likely to
      have allergic sensitization than those fed formula only (relative risk [RR], 1.5;
      95% confidence interval [CI], 1.1-2.1). Although the estimates are imprecise,
      this RR was higher for children born to mothers reporting a history of allergy
      (RR, 1.8; 95% CI, 1.0-3.0) than for those born to mothers with no allergic
      history (RR, 1.3; 95% CI, 0.9-2.1), for children in households without (RR, 1.6;
      95% CI, 1.1-2.2) vs with (RR, 1.0; 95% CI, 0.3-4.0) multiple pets, and for those
      with an older sibling (RR, 2.0; 95% CI, 1.2-3.3) vs firstborns (RR, 1.3; 95% CI,
      0.8-2.1). CONCLUSIONS: Breastfeeding without formula supplementation may be
      associated with an increased risk of childhood allergies. However, this
      association may vary with birth order, exposure to household pets, and maternal
      allergic history.

PMID- 16892787
TI  - Relationship between childhood atopy and wheeze: what mediates wheezing in atopic
      phenotypes?
AB  - BACKGROUND: The nature of the relationship between childhood wheeze and atopy
      remains uncertain. OBJECTIVE: To characterize childhood wheeze among atopic
      phenotypes in a longitudinal birth cohort study. METHODS: A whole population
      birth cohort (N = 1,456) was recruited in 1989. Children were seen at birth and
      at 1, 2, 4, and 10 years of age to obtain information on asthma and allergic
      disease development and relevant risk factors for these states. Skin prick
      testing at ages 4 (n = 980) and 10 (n = 1,036) years was used to define atopic
      phenotypes. Wheezing in these states was characterized, and logistic regression
      was used to identify independent risk factors for wheeze onset in different
      atopic phenotypes. RESULTS: Wheeze ever occurred in 37% of never atopics, 38% of
      early childhood atopics, 65% of chronic childhood atopics, and 52% of delayed
      childhood atopics. Chronic childhood atopics had significant wheezing morbidity
      and bronchial hyperresponsiveness. Their wheezing was associated with male sex,
      early eczema, family history of eczema, and early tobacco exposure. Never atopic
      wheeze was related to maternal asthma, parental smoking, and respiratory tract
      infections. Exclusive breastfeeding protected against early childhood atopic
      wheeze. Maternal asthma, family history of urticaria, and dog ownership increased
      delayed childhood atopic wheeze. CONCLUSIONS: In many respects, chronic childhood
      atopy is the atopic phenotype associated with the most significant forms of
      childhood wheezing. In such children, heritable drive, allergens, and synergy
      with other environmental triggers seem to be crucial determinants of wheeze
      onset. Where such sensitization is absent, numerous environmental factors plus
      genetic predisposition may assume importance for wheezing.

PMID- 16892788
TI  - Flexible approaches in the design of subcutaneous immunotherapy protocols for
      Hymenoptera venom allergy.
AB  - BACKGROUND: Venom immunotherapy is an effective method for the treatment of
      Hymenoptera venom allergy. Different extracts and treatment schedules are
      available. OBJECTIVE: To compare the safety and efficacy of immunotherapy in 3
      cohorts of patients sensitized to Vespula species. METHODS: In this open study,
      43 patients were treated with a subcutaneous aqueous extract for induction and
      maintenance (AA), 34 with a subcutaneous depot extract for induction and
      maintenance (DD), and 29 with subcutaneous aqueous and subcutaneous depot
      extracts for induction and maintenance, respectively (AD). Cluster schedules were
      followed to reach maintenance, and adverse effects during treatment and after
      naturally occurring stings were recorded. RESULTS: Depot immunotherapy was better
      tolerated mainly owing to the lower frequency of local adverse effects in the
      induction phase (5.9% vs 42.5% and 1.3% vs 5.1% on a per patient and per dose
      basis, respectively; P < .001 for both) and for effects occurring within 60
      minutes after vaccination (2.9% vs 19.2% and 0.2% vs 2.8% on a per patient and
      per dose basis; P = .03 and P < .001, respectively). Furthermore, 19 of 20 AA, 9
      of 9 AD, and 10 of 10 DD patients who were restung experienced only minor local
      effects. CONCLUSIONS: Venom immunotherapy is efficacious. Although there was no
      decrease in systemic reactions, depot immunotherapy to Vespula venom induced
      fewer early local adverse effects. Patients undergoing an induction phase with an
      aqueous extract can benefit from switching to a depot extract during maintenance.
      Increasing the flexibility of the immunization schedules may improve compliance
      with this potentially lifesaving treatment.

PMID- 16892789
TI  - Onset and duration of protection against exercise-induced bronchoconstriction by
      a single oral dose of montelukast.
AB  - BACKGROUND: Leukotriene modifiers have been shown to protect against exercise
      induced bronchoconstriction (EIB) with repeated, chronic dosing. OBJECTIVE: To
      study the onset and duration of protection against EIB after a single dose of
      montelukast, a leukotriene receptor antagonist. METHODS: In this randomized,
      crossover, double-blind study, 51 adult asthma patients with EIB (> or = 20%
      postexercise decrease in forced expiratory volume in 1 second [FEV1]) received a
      single oral dose of montelukast (10 mg), or placebo followed by exercise
      challenge 2, 12, and 24 hours after dosing. The primary end point was maximum
      percentage decrease in FEV1 from preexercise baseline during 60 minutes after the
      2-hour challenge. RESULTS: At 2, 12, and 24 hours after dosing, the maximum
      decrease in FEV1 was 10.8% +/- 7.9%, 8.4% +/- 7.5%, and 8.3% +/- 7.3% for
      montelukast and 22.3% +/- 13.1%, 16.1% +/- 10.2%, and 16.9% +/- 11.7% for
      placebo, respectively (P < or = .001 at each time point). Postexercise recovery
      was quicker with montelukast than with placebo (P < or = .001); mean (95%
      confidence interval) differences were -26.8 minutes (-35.1 to -18.4 minutes), 
      16.0 minutes (-22.9 to -9.2 minutes), and -17.4 minutes (-24.9 to -9.9 minutes)
      at the 3 time points, respectively. At all time points, area under the curve for
      percentage decrease in FEV1 during 60 minutes after exercise was smaller after
      montelukast (P < or = .001); montelukast protected more patients against EIB (P <
      or = .001). Fewer patients required postexercise beta-agonist rescue at 2 hours
      after dosing with montelukast (P = .03). CONCLUSION: Montelukast provided
      significant protection against EIB as soon as 2 hours after a single oral dose,
      with persistent benefit up to 24 hours.

PMID- 16892790
TI  - Safety of etoricoxib, a specific cyclooxygenase-2 inhibitor, in asthmatic
      patients with aspirin-exacerbated respiratory disease.
AB  - BACKGROUND: Treatment of rheumatic conditions is limited in patients with asthma
      owing to concerns of nonsteroidal anti-inflammatory drugs potentially provoking
      asthma. Cross-sensitivity to all anti-inflammatory drugs that inhibit
      cyclooxygenase enzymes occurs in these individuals. OBJECTIVES: To study the
      safety of etoricoxib, a specific cyclooxygenase-2 inhibitor, and to determine
      whether it cross-reacts with asthma in patients with aspirin-exacerbated
      respiratory disease (AERD). METHODS: This study included 77 patients who had
      experienced asthma induced by aspirin and at least 1 other nonsteroidal anti
      inflammatory drug. Baseline evaluation included blood pressure measurement, nasal
      examination, spirometry, and peak expiratory flow rate measurement. Patients were
      given placebo the first day and then were challenged with once-daily etoricoxib
      in 3 different doses: 60 mg on day 2, 90 mg on day 3, and 120 mg on day 4. If no
      evidence of intolerance was seen, each patient was rechallenged with 60 or 90 mg
      of etoricoxib once daily (according to the rheumatic condition) 7 days later.
      Reassessment of the baseline measurements was performed daily from day 1 to day 4
      after the initial challenge, on day 7 after rechallenge, and after 1 month of
      drug intake. If the patient developed any mucosal or skin reaction, hypotension,
      upper or lower airway obstruction, conjunctival reaction, or laryngeal edema
      during the challenge test, it was considered a positive response. RESULTS:
      Etoricoxib was well tolerated, without any signs of immediate or delayed
      hypersensitivity in aspirin- and nonsteroidal anti-inflammatory drug-induced
      asthmatic patients. None of 77 study patients experienced any symptoms or
      developed dyspnea, change in nasal examination, significant variation in peak
      expiratory flow rate greater than 20%, or decline in forced expiratory volume in
      1 second greater than 15% during etoricoxib challenge. The exact 1-sided
      confidence interval for the probability of etoricoxib inducing cross-reactions in
      patients with AERD was 0% to 2%. CONCLUSIONS: These results confirm the lack of
      cross-reactivity between specific cyclooxygenase-2 inhibitors and aspirin in
      AERD. Etoricoxib was safe for treating inflammation in patients with AERD.

PMID- 16892791
TI  - New-onset rheumatoid arthritis after anthrax vaccination.
AB  - BACKGROUND: Anthrax vaccine was licensed in 1970 and is used to protect
      individuals exposed to biological warfare and those who may come in contact with
      Bacillus anthracis in infected animals or in laboratory settings. The current
      adsorbed anthrax vaccine is regarded as effective and safe. Adverse effects
      reported include fever, chills, myalgia, arthralgia, and nausea. Four cases of
      rheumatoid arthritis (RA) temporally related to anthrax vaccine have been
      reported. As the number of administered doses increases, a better understanding
      of its adverse events profile will be forthcoming. OBJECTIVE: To describe another
      patient with RA temporally related to anthrax vaccination. METHODS: A 42-year-old
      man developed bilateral knee stiffness and pain in all the proximal
      interphalangeal joints 5 days after receiving the first dose of anthrax vaccine.
      He reported chills, fever, and joint and neck pain, with a tender nodule at the
      injection site after dose 2. Hours after receiving dose 3 he experienced fever,
      chills, nausea, vomiting, and neck, hand, and shoulder pain. The vaccination
      series was terminated after the third dose. RESULTS: Physical examination
      revealed moderate swelling and tenderness of his bilateral proximal
      interphalangeal joints. His complete blood cell count was normal; rheumatoid
      factor level, 198 IU/mL; erythrocyte sedimentation rate, 53 mm/h; antinuclear
      antibodies, negative; C-reactive protein level, 2.7 mg/L; and anti-cyclic
      citrullinated peptide antibody level, 168 EU. Radiographs revealed mild
      degenerative changes in his hands and knees bilaterally. CONCLUSIONS: This case
      represents a fifth patient with RA temporally related to anthrax vaccine.

PMID- 16892792
TI  - Effects of long-term low-dose corticosteroid therapy on humoral immunity.
AB  - BACKGROUND: Corticosteroids are agents that suppress the immune system. Their
      suppressive activity is predominantly restricted to cell-mediated immunity, with
      a marginal inhibitory effect on humoral immunity. OBJECTIVE: To describe an
      acquired reversible B-cell deficiency in a patient treated with low-dose
      corticosteroids for 36 years. METHODS: A broad range of T- and B-cell parameters
      were studied over time, during and after discontinuation of corticosteroid
      therapy. Published works on this topic in animal and human models are reviewed.
      The findings unique to this patient are highlighted. RESULTS: While undergoing
      long-term corticosteroid therapy, a patient developed a clinical and immunologic
      picture suggestive of common variable immunodeficiency, with predominantly
      qualitative and quantitative B-cell abnormalities. These abnormalities resolved
      within 2 years after tapering of corticosteroid therapy. CONCLUSIONS: Long-term
      low-dose corticosteroid use may reversibly decrease B-cell counts and specific
      antibody responses.

PMID- 16892794
TI  - Diphenhydramine vs desloratadine comparisons must consider risk-benefit ratio.

PMID- 16892793
TI  - The black box warning for topical calcineurin inhibitors: looking outside the
      box.

PMID- 16892795
TI  - Emergency department treatment of anaphylaxis: is epinephrine always indicated?

PMID- 16892796
TI  - [Expression of transforming growth factor beta1 and insulin-like growth factor I
      in the regenerated bones after low frequency micro movement].
AB  - OBJECTIVE: To investigate the expression of transforming growth factor beta1 (TGF
      beta1) and insulin-like growth factor I (IGF-I) in new bone after low frequency
      micro movement. METHODS: Fifteen female sheep from Shandong province were
      involved in the study and their bilateral tibias transversely osteotomized in the
      middle shafts with a defect of 2 mm. The hind limbs were fixed with unilateral
      external fixators connected to a controlled micro movement device. Ten days after
      osteotomy, one hind limb of each sheep randomly was selected to perform micro
      movement at an amplitude of 0. 25 mm and a frequency of 1 Hertz, 30 min a day for
      4 weeks (micro movement group). The other hind limb served as the control group.
      Five sheep were sacrificed at 3, 4 and 6 weeks after osteotomy, respectively, and
      specimens were harvested for detecting the expression of TGF-beta1 and IGF-I by
      immunohistochemistry and RT-PCR. RESULTS: Immunohistochemistry: In the third
      postoperative week in the micro movement group, the expression of TGF-beta1 was
      detected in different areas of new chondrocytes at the margin of callus, mainly
      in proliferating area, and IGF-I expressed in osteoblasts at the margin of
      endochondral ossification area, calcified and mature chondrocytes and osteocytes.
      There was seldom expression of IGF-I and little expression of TGF-beta1 in the
      corresponding area in the control one. In the 4th postoperative week in the micro
      movement group, the expression of TGF-beta1 diminished gradually with the mature
      of new bone and be located in extracellular matrix and osteoblasts around
      ossified areas; The expression of IGF-I reached the peak and be located mainly in
      osteoblasts of new bone surface, maturing osteocytes and calcifying osteoid. But
      there was little expression of them in the control group. In the sixth
      postoperative week in the micro movement group, there was a little expression of
      IGF-I expression but little expression of TGF-beta1; there was nearly no
      expression of them in the control group. In the micro movement group, the
      absorbance values of TGF-beta1 at 3 and 4 weeks and of IGF-I at 3, 4 and 6 weeks
      were significantly higher than those in control group (P<0. 05). RT-PCR: In the
      third and fourth postoperative weeks in the micro movement group, there was
      higher expression of mRNA of TGF-beta1 and TGF-I than those in control group; in
      the sixth postoperative week, the expression diminished gradually, but was higher
      than that in control group. The absorbance values of TGF-beta1 at 3 and 4 weeks
      and IGF-I at 3, 4 and 6 weeks were significantly higher than those of control
      group (P<0. 05). CONCLUSION: Low frequency and controlled micro movement in the
      early stage of the fracture healing can promote the expression of TGF-beta1 and
      IGF-I. They worked together to regulate the process of the endochondral
      ossification, while in the late stage the differentiation of osteocytes and
      mineralization of osteoid were regulated mainly by IGF-I, which played an
      important role in regulating the cell biological behavior during micro movement.

PMID- 16892797
TI  - [Comparison of various kinds of internal fixations in unstable intertrochanteric
      femoral fracture].
AB  - OBJECTIVE: To explore the effects of various kinds of internal fixations on
      unstable intertrochanteric femoral fractures. METHODS: From January 2000 to
      December 2004, 88 cases of unstable intertrochanteric femoral fractures were
      treated. There were 52 males and 36 females (aged 19-86 years). Twenty-two cases
      were caused by fall from height, 36 by motor vehicle accident and 20 by fall and
      10 by tumble. They were divided into 4 groups according to 4 kinds of internal
      fixations: dynamic hip screw (DHS, group A, n=42), anatomical proximal femur bone
      plate (group B, n = 23), proximal femoral nail (PFN, group C, n = 8)and dynamic
      condylar screw (DCS, group D, n = 15). According to the modified Evan's
      classification, fractures were all unstable type and were classified as follow
      types: group A (15 type III, 8 type IV and 19 type V); group B (12 type III, 5
      type IV and 6 type V); group C (3 type III, 2 type IV and 3 type V); and group D
      (10 type III, 3 type IV and 2 type V). The data of operative time, intra
      operative blood loss, intra-operative complications, fluoroscopy exposures,
      clinical healing time of fracture, post-operative restored function and
      postoperative complications were recorded and analyzed statistically using the
      SPSS 12.0 software package. RESULTS: All patients were followed up for 12-48
      month (18 months on average). All patients achieved clinical healing. Coxa varus
      occurred in 3 cases of group A, in 1 case of group C and in 3 cases of group D.
      The differences were of no statistical significance in operative time and
      postoperative complications between 4 groups (P>0.05). The difference was of
      statistical significance in the blood loss between groups A, B and groups C, D
      (P<0.05) but no statistical significance between group C and group D (P>0.05).
      The difference was of statistical significance in the fluoroscopy exposures,
      clinical healing time of fracture and postoperative complications between group B
      and the other groups (P<0.05). The difference was of statistical significance in
      the post-operative restored functions between group D and the other groups
      (P<0.05). CONCLUSION: The anatomical proximal femur bone plate is a useful device
      in the treatment of unstable intertrochanteric femoral fracture. The operative
      manipulation is simple and the hip functions recover well.

PMID- 16892798
TI  - [Exploration of surgical approaches of complex tibial plateau fractures].
AB  - OBJECTIVE: To evaluate the surgical treatment and its results of complex tibial
      plateau fractures. METHODS: From May 2003 to November 2004, 24 cases of complex
      tibial plateau fractures were treated by two-incision approaches. There were 16
      males (including 1 case of bilateral), and 8 females, with mean age of 40.6 years
      (21-65 years), eleven fractures occurred in left extremity and 14 in the right.
      No patients suffered open fractures. Fracture was caused by fall from height in
      10 cases, by traffic accident in 12 cases and by another causes in 2 cases.
      According to Schatzker classification, type V fracture was found in 14
      extremities, type VI in 11 extremities. All cases were operated with two-incision
      approaches and double-plates fixation. The operation was performed 6-15 days
      after injury with mean 10.4 days. RESULTS: All cases were followed up from 12 to
      23 months (mean 15.6 months). Time of the bone healing was 6-9 months, with mean
      7.4 months. No reduction of anatomy was achieved because of comminuted fractures
      of articular surfaces in 2 limbs. The line of the lower extremity did not recover
      because of metaphysis comminution in 1 limb, which led to knee varus. Epidermal
      necrolysis was observed in 3 limbs, and the wound healed after change dressing.
      The function of the knee was evaluated according to Rasmussen's criteria, the
      results were excellent in 10 limbs, good in 8 limbs, fair in 3 limbs, and poor in
      4 limbs. CONCLUSION: The two-incision approaches reduced the complication of soft
      tissue injury, which is conductive to reduction of articular surface. Double
      plates provide a sufficient internal fixation. It can permit early motion of knee
      joint. Therefore, two-incision approach are an effective surgical approach of
      treatment of complex tibial plateau fractures.

PMID- 16892799
TI  - [Treatment of comminuted inferior femoral fractures with combination of
      supracondylar locked intramedullary nail and shape memory block hoop internal
      fixator under arthroscopy].
AB  - OBJECTIVE: To investigate the advantages and the clinical outcomes of the
      treatment of comminuted inferior femoral fractures with combination of
      supracondylar locked intramedullary nail and shape memory block hoop internal
      fixator under arthroscopy. METHODS: From June 2002 to December 2004, 12 cases of
      comminuted inferior femoral fractures were treated (9 males, 3 females). Of them,
      5 cases were classified as type B and 7 cases as type C according to AO
      classification. All cases were treated with combination of supracondylar locked
      intramedullary nail and shape memory block hoop internal fixator under
      arthroscopy. In 12 cases of one-stage bone grafting, there 5 of autologous
      cancellous bone grafting and 7 allo-freeze drying bone grafting. RESULTS: With a
      follow-up of 6 to 18 months, all fractures healed within 3 to 6 months. There
      were no infection and nonunion. The function of all the knees joint was
      excellent. According to Noye's criterion for knee scoring, the results were
      excellent in 9 cases and good in 3 cases; the excellent and good rate was 100%.
      CONCLUSION: It is a good method to treat comminuted inferior femoral fractures
      with combination of supracondylar locked intramedullary nail and shape memory
      block hoop internal fixator under arthroscopy. It has many advantages of less
      injury to knee joint, good anatomic reduction and reliable fixation.

PMID- 16892800
TI  - [Treatment of comminuted fractures at distal femur and proximal tibia with less
      invasive stabilization systems].
AB  - OBJECTIVE: To study the clinical outcome of comminuted fractures at distal femur
      and proximal tibia treated with AO less invasive stabilization systems (LISS).
      METHODS: The clinical data of 14 cases of distal femoral fracture and proximal
      tibial fracture from September 2003 to May 2005 were analyzed retrospectively.
      The injury was caused by traffic accident in 9 cases, by fall in 3 cases and by
      slipping in 2 cases. Of 14 cases, there were 5 open fractures and 9 close
      fractures, including 5 cases of distal femoral comminuted fracture and 9 cases of
      proximal shaft comminuted fractures. According to AO/OTA classification, the
      fractures were classified as 33C2 in 3 cases, 33C3 in 2 cases, 41A2 in 2 cases,
      41A3 in 2 cases, 41B2 in 3 cases and 41C2 in 2 cases. All patients were treated
      by the internal fixation with LISS-distal femur or with LISS-proximal tibia.
      Healing of wounds, the X-ray films before and after operations, and the recovery
      of joint function were observed. RESULTS: The patients were followed up from 1
      month to 20 months (11 months on average). Twelve cases achieved solid osseous
      unions from 3 months to 5 months postoperatively; 2 cases had a good reduction
      and recovered smoothly 2-3 months postoperatively. The results were excellent in
      10 cases, good in 3 cases and fair in 1 case according to Johner-Wruhs knee
      scoring. The range of knee flexion-extension was 110-130 degrees in 11 cases, 100
      degrees in 2 cases and 80 degrees in 1 case. CONCLUSION: LISS is an effective
      method of internal fixation for treating comminuted fracture of distal femur or
      proximal tibia. It has the advantages of less injury, satisfied reduction and
      reliable fixation.

PMID- 16892801
TI  - [Internal fixation with the supporting steel of AO femoral condyles for treatment
      of complicated distal femoral fractures].
AB  - OBJECTIVE: To explore the technique and clinical effects of internal fixation of
      complicated distal femoral fractures using the supporting steel of AO femoral
      condyles. METHODS: From October 2001 to February 2004, 23 cases of complicated
      distal femoral fractures were treated with open reduction and internal fixation
      using the supporting steel of AO femoral condyles. Of 23 cases, there were 19
      males and 4 females, aged 27-55 years. The locations were the right side in 10
      cases and the left side in 13 cases. Fracture caused by traffic accident in 16
      and by fall in 7, including 14 closed fracture and 9 open fracture, 21 fresh
      fracture and 2 old fracture. According to AO classification, 6 cases were
      classified as type A extra-articular fracture and 17 cases as type C intra
      articular fracture. The X-ray films before operation showed comminuted fracture
      of femoral intercondylar and femoral supracondylar. All cases received scientific
      and rational rehabilitative treatment post-operatively. RESULTS: The
      postoperative follow-up ranged from 6 months to 20 months, 23 cases achieved
      fracture healing with an average healing period of 10.3 months (from 7 months to
      16 months). According to the criteria of Kolmer and Wulff, the results were
      excellent in 16 cases, good in 4 cases, fair in 2 case and poor in 1 case. The
      excellent and good rate was 86.9%. CONCLUSION: Internal fixation with the
      supporting steel of AO femoral condyles for treatment of complicated distal
      femoral fractures has advantages of reasonable design, convenient operation, firm
      fixation and reliable clinical outcome.

PMID- 16892802
TI  - [Contrast analysis of different sagittal split ramus osteotomy methods in
      correcting mandibular prognathism].
AB  - OBJECTIVE: To explore the indication, advantage and disadvantage of modified or
      classical technique of intraoral sagittal split ramus osteotomy (SSRO) for
      correction of mandibular prognathism. METHODS: From January 1997 to January 2005,
      95 patients suffering from mandibular prognathism or accompanied by other
      deformities were treated with modified or classical technique of intraoral SSRO.
      Of 95 cases, there were 34 males and 61 females, aging 15 to 44 years, including
      53 cases of single mandibular prognathism, 28 cases accompanied with mandibular
      deviation, 11 cases accompanied with maxillary retrognathism, 2 cases accompanied
      with glossacele and 1 case accompanied with malar protrusion. X-ray cephalometry
      showed: sella-nasion-A point (SNA) 80-83 degrees, sella-nasion-B point (SNB) 80
      84 degrees, A point-nasion-B point (ANB)--3-1 degrees. Forty-three cases were
      corrected by modified SSRO and 52 cases by classical SSRO. RESULTS: The face
      appearance and dental articulation of all the patients were improved greatly. In
      patients by classical SSRO, disorder of local sensibility occurred in 9 cases,
      mandibular fracture during the cleavage of the ascending ramus in 1 case,
      significant bleeding in 1 case, postoperative infection in 1 case and
      postoperative relapse in 3 cases. In patients by modified SSRO, disorder of local
      sensibility occurred in 2 cases and postoperative relapse in 1 case; no
      mandibular fracture, significant bleeding, postoperative infection and other
      complications occurred. With a follow-up of 3 months to 7 years, X-ray
      cephalometry showed SNA 81-83 degrees, SNB 78-81 degrees and ANB 1-4 degrees.
      CONCLUSION: Modified SSRO is an ideal method of correcting mandibular
      prognathism, especially severer mandibular prognathism accompanied by mandible
      deviation deformity.

PMID- 16892803
TI  - [Parameters to judge the stability of wrist after the four-corner arthrodesis].
AB  - OBJECTIVE: To find out some parameters to judge the stability of the wrists after
      tour-corner arthrodesis and to explore the strategy for improving the range of
      motion (ROM) of the wrist after four-corner arthrodesis. METHODS: After the
      simulated four-corner arthrodesis was performed in both wrists of 8 men and 4
      women cadaver, the wrists were fixed on the wrist motor simulator; and wrist
      movement including flexion, extension, radial deviation, ulnar deviation was
      simulated. The standard posteroanterior and lateral radiographs were taken for
      measuring the change of capitolunate angle (alpha), radiolunate angle (beta),
      capitolunate posteroanterior angle (theta), the height (H) and width (W) of the
      fused four carpal bone bloc. RESULTS: There were statistically significant
      differences in alpha, beta, theta angles (P<0.01) in the case of 50 degrees
      flexion or 40 degrees extension, and in H and W values (P<0.05) in the case of 25
      degrees ulnar deviation or 15 degrees radial deviation when compared with before
      movement. CONCLUSION: Capitolunate angle, radiolunate angle, capitolunate
      posteroanterior angle, the height and the width of the fused four carpal bone
      bloc can be used to judge the stability of the wrists after four-corner
      arthrodesis.

PMID- 16892804
TI  - [Study on mechanism of the circulation reconstructing of skin flap after early
      repeated short ischemia training].
AB  - OBJECTIVE: To investigate the effects of repeated short ischemia training on flap
      survival area, vascular endothelial growth factor and the microvascularsel
      density. METHODS: Seventy-two rabbits were divided into: the experimental group
      (n=64), the skin flaps were constructed in two sides of back, one side flap were
      given ischemia training for 15 minutes and 8 times one day at the pedicles from
      the 1st to 8th day after operation (group A), the other side flap was served as a
      control (group B), the corresponding site was only marked as a blank control
      group (group C). Then, 8 pedicles of group A and group B were isolated every day.
      The surviving area of all skin flaps were calculated on the 5th day after
      isolating operation. The vascular endothelial growth factor (VEGF) and
      microvessel density(MVD) of the 3 groups were checked with
      immunohistologochemical staining. RESULTS: After the operation, all animals were
      survival with normal vitality. The survival flap area of group A were significant
      more than that of group B after 3 days (P<0.05). The expressions of VEGF and MVD
      of group A and group B were higher than group C. The expression of VEGF of group
      A was significantly higher than that of group B (P<0.01). The counting of MVD of
      group A was also significantly higher than that of group B (P<0.05). There was
      positive correlation between flap survival area and MVD in group A. The relation
      of time point was n and n-2 respectively,correlation coefficient was 0.850. As
      well as MVD and VEGF were positive correlation, correlation coefficient was
      0.801. CONCLUSION: Early repeated short ischemia training can increase flap
      survival area, the mechanism maybe involve the increased expression of VEGF,
      which can increased skin flap microvascular density.

PMID- 16892805
TI  - [Application of Doppler in the skin flap of vastus lateralis].
AB  - OBJECTIVE: To investigate a method of improving design of the skin flap pedicled
      with descending branch of lateral femoral circumflex artery, in order to increase
      the accuracy of preoperative Doppler location. METHODS: Firstly, the interspace
      between rectus femoris and vastus lateralis was regarded as line A, and the point
      of intersection between line A and the vertical line through the midpoint of the
      line between anterior superior iliac spine and lateral margin of patella was
      point A. And then the line between the midpoint of groin and point A was regarded
      as line B. Based on this , the perforating point of cutaneous branch could be
      located by Doppler along the line B. From November 2001 to October 2004, this
      method was used in 38 skin flaps of 37 cases, being all males and 16-48 years
      old. The area of the flap ranged from 7 cm x 6 cm to 24 cm x 16 cm. RESULTS: All
      the perforating point of cutaneous branch were located outward the line A. The
      rate that the preoperative Doppler location was consistent with the utility point
      of formatting skin flap was 97.4%. All the cases were followed up postoperatively
      1-20 months. Among the cases, 36 skin flaps of 35 cases was successful and only 2
      skin flaps partially necrosed, which healed after changing dressings or skin
      graft. Out of 35 cases, the sensation restoration of the skin flap was S2-S3 in 6
      cases owing to the anastomosis of lateral femoral cutaneous nerve and a skin
      nerve of the recipient site, while that of the other cases was S0-S1. CONCLUSION:
      Preoperative Doppler location and improving design of line B can be a useful
      instruction for the design of skin flap pedicled with descending branch of
      lateral femoral circumflex artery.

PMID- 16892806
TI  - [Transfer of neurovascular island flap from the same finger for repairing pulp
      defect].
AB  - OBJECTIVE: To observe the clinical effects of neurovascular island flap from the
      same finger for repairing pulp defect. METHODS: From November 2003 to February
      2005, 32 pulp defects in 30 cases were covered with neurovascular island flap
      from the same finger. There were 25 males and 5 females. The age ranged from 18
      to 56 years. The operation was performed after debridement and 2-8 days
      antibiotics therapy. The defect area ranged from 1.5 cm x 1.2 cm to 3.5 cm x 2.1
      cm. The flap was harvested on the dorsal part of the finger ulnarly or radially.
      The distal end of the flap should be more than 5 mm away from the nail base to
      avoid nail injury. The ventral and dorsal cut should not exceed the middle line
      respectively. The flap size ranged from 2.0 cm x 1.5 cm to 4.0 cm x 2.5 cm. The
      donor site was covered with flap of subdermal vascular plexus from the medial
      side of the upper arm. RESULTS: All 32 transferred flaps survived after
      operation. There was no vascular crisis. Twenty-five cases were followed up from
      2 to 8 months. The flaps had good appearance and texture and blood circulation.
      Two-point discrimination was 7-10 mm. The function of finger motion was returned
      to normal. CONCLUSION: Transfer of neurovascular island flap from the same finger
      offered a sensational skin flap for reconstruction of pulp defect. The technique
      was simple, and the clinical result was satisfactory. It is an ideal method for
      reconstruction of thumb or finger pulp defects.

PMID- 16892807
TI  - [Clinical application of irregular anterior lateral femoral flap in hand
      surgery].
AB  - OBJECTIVE: To introduce a method to repair soft tissue defect in different
      regions and different areas of hand in one procedure. METHODS: From May 2002 to
      May 2005, anterolateral femoral flap or lobulated anterolateral femoral flap
      (forming irregular anterolateral femoral flap) was designed into different shapes
      to repair multiple soft tissue defect in different regions in hand, which was
      used clinically in 27 cases. Among 27 cases, there were 16 males and 11 females;
      the locations were left hand in 9, right hand in 16 and left foot in 2; including
      5 penetrating injury, 9 hot pressing injury, 2 soft tissue defection of instep
      and plantae by milled injury, 6 gearing injury and 5 carding machine injury. All
      the cases complicated by exposure of tendons, bones or joints. Defect was
      repaired with H-shape flaps in 5 cases of penetrating palm injuries; with Y-shape
      or K-shape flaps in 11 cases of dorsal or combined with fingers of hand with skin
      defect; with perpendicular-shape flaps in 3 cases of dorsal combined with sides
      of palms or the first web of hands with skin defect and in 2 cases of skin
      defects of dorsal combined with palms of feet; with h-shape flaps in 6 cases of
      skin defects of dorsal or palms combined with disconnected skin defect of
      fingers. The sizes of main flaps ranged from 6.5 cm x 4.8 cm to 17.0 cm x 12.0
      cm, the sizes of lobulated flaps ranged from 3.5 cm x 2.8 cm to 7.5 cm x 4.5 cm.
      RESULTS: All flaps survived without vascular crisis after operation. Except the
      fascia flap all recipient sites healed by first intention. The follow-up period
      ranged from 3 months to 1 year, all cases had satisfactory appearance, the
      texture of flaps was soft. Except 2 cases of penetrating injury, 3 cases of hot
      pressing injury and 1 case of carding machine injury whose function was not
      satisfactory, the remaining cases achieved the function of snap and pinch. More
      than 1 year after operation, the sense of pain and touch recovered. There was no
      functional impairment at the donor sites although scar hyperplasia was formed in
      some cases. CONCLUSION: The application of irregular anterolateral femoral flap
      is an optimal choice for complex skin defect of hand.

PMID- 16892808
TI  - [Reconstruction of infected median sternotomy wound dehiscence after coronary
      artery revascularization].
AB  - OBJECTIVE: To introduce the experience about the reconstruction of median
      sternotomy wound dehiscence. METHODS: From February 2002 to October 2004, 10
      patients with median sternotomy wound dehiscence due to coronary artery
      revascularization were treated. There were 7 males and 3 females, aging from 68
      to 76 years. The sizes of defects ranged from 3 cm x 5 cm to 5 cm x 15 cm. After
      debridement of necrotic soft tissue, sternum and rib, infected median sternotomy
      wound was reconstructed with rectus abdominis myocutaneous flap, pectoralis major
      myocutaneous flap and latissimus dorsi flap or single muscle flap. The sizes of
      flaps ranged from 3 cm x 5 cm to 5 cm x 16 cm. RESULTS: All patients were
      followed up from 3 to 11 months with an average of 6 months. All the patients
      achieved healing by first intention with normal respiration and normal function
      of upper limbs. The wound of donor site healed well. No abdominal hernia and
      other complications occurred. The wound of donor site healed well. The results
      were satisfactory. CONCLUSION: According to different stages of the disease and
      different conditions of an operation, the surgical management should vary with
      each individual.

PMID- 16892809
TI  - [Clinical study on application of bovine amnion on burn wounds].
AB  - OBJECTIVE: To observe clinical effects of burn wounds treatment with bovine
      amnion and to screen the best method of preparing and storing of bovine amnion.
      METHODS: From January 2004 to January 2005. We selected randomly 58 patients with
      superficial secondary wound, deep secondary wound, autografting area for removal
      of eschars and tangential excision, fetching skin area or residual burn wound .
      Using auto-control, every burn wound was divided into 3 parts and was treated
      with 3 dressings: bovine amnion dealt with by 0.1% chlorhexidine (group A),
      bovine amnion dealt with by 0.4% glutaraldehyde (group B) and vaseline gauze
      dressing (group C as control). The clinical effects were compared between
      different groups and the method of preparing and storing bovine amnion was
      evaluated. RESULTS: The dressing texture of group A was softer than that of group
      B, and its flexibility was fine. The pre-treatment was not necessary for dressing
      in group A. When the dressing was used on burn wounds in groups A and B, pain was
      slight, but pain was obvious in group C; healing time in groups A and B was much
      less than that in group C, showing statistically significant difference (P<0.01).
      There was no statistically significant difference in healing time between groups
      A and B (P>0.05). The infection ratio of burn wound in deep secondary wound and
      residual burn wound of groups A and B is much lower than that of group C, showing
      statistically significant difference (P<0.05); in the other burn wounds there was
      no significant difference (P>0.05). There was no statistically significant
      difference between groups A and B (P> 0.05). CONCLUSION: Bovine amnion could make
      benefit on burn wounds healing, reduce infection ratio of burn wounds, could be
      used on different kinds of burn wounds. The clinical effect between bovine amnion
      dealt with by glutaraldehyde and by chlorhexidine is similar. Whereas the latter
      is more easy to be popularized.

PMID- 16892810
TI  - [Clinical application of peroneal muscles tendon transposition in repair of
      Achilles tendon rupture].
AB  - OBJECTIVE: To discuss applied anatomy, biomechanics and surgical procedures of
      long peroneal muscles tendon transposition in repair of occlusive achilles tendon
      rupture. METHODS: The blood supply and the morphology of long peroneal muscles
      tendon were observed in the lower extremity of 50 sides adult specimens and the
      mechanical tests which stretch load on the tendon were carried out. The methods
      were designed on the basis of the anatomical characteristics and morphology. Ten
      patients suffering occlusive Achilles tendon rupture were treated by using long
      peroneal muscles tendon transposition from March 2001 to July 2004. Among 10
      patients, there were 7 males and 3 females, aging 32 to 54 years including 6
      cases of jump injury, 2 cases of bruise, 1 case of step vacancy and 1 case of
      spontaneity injury. The interval between injury and surgery was 6 hours to 7 days
      in 7 fresh rupture and 21 days to 3 months in 3 old rupture. All cases belonged
      to occlusive Achilles tendon rupture (8 cases of complete rupture and 2 cases of
      incomplete rupture). RESULTS: The origin of long peroneal muscles was proximal
      tibia and fibular head, the end of them was base of first metatarsal bones and
      medial cuboid. The length of tendon was 13.5 +/- 2.5 cm. The width of origin
      tendon was 0.9 +/- 0.2 cm and the thickness was 0.3 +/- 0.1 cm; the width on apex
      of lateral malleolus was 0.7 +/- 0.1 cm and the thickness was 0.4 +/- 0.1 cm, the
      width on head of cuboid was 0.7 +/- 0.1 cm and the thickness was 0.3 +/- 0.1 cm.
      The long peroneal muscles tendon had abundant blood supply. The results of
      mechanical test showed that the biggest load was 2,292.4 +/- 617.3 N on tendon
      calcaneus, 1,020.4 +/- 175.4 N on long peroneal muscles tendon, 752.0 +/- 165.4 N
      on peroneus brevis tendon and 938.2 +/- 216.7 N on tibialis posterior tendon. Ten
      cases of occlusive Achilles tendon rupture achieved healing by first intention
      and were followed up 18-24 months. No Achilles tendon re-rupture, necrosis of
      skin or other complications occurred. According to Amerind-holm criterion for
      curative results, the results were excellent in 7 cases and good in 3 cases and
      the excellent and good rate was 100%. CONCLUSION: The long peroneal muscles
      tendon transposition is a perfect and simple way to repair occlusive Achilles
      tendon rupture.

PMID- 16892811
TI  - Comparison of clinical outcomes between two methods of posterior lumbar interbody
      fusion in adult spondylolisthesis.
AB  - OBJECTIVE: To compare the clinical outcomes of posterior lumbar interbody fusion
      (PLIF) using simple cage alone fusion with pedicle screw fixation and autogenous
      bone grafting and cage fusion with pedicle screw fixation in adult
      spondylolisthesis. METHODS: From March 2003 to March 2004, twenty-seven patients
      with lumbar spondylolisthesis were divided in two groups. In group A, 15 patients
      were treated by PLIF using simple cage alone fusion with pedicle screw fixation,
      including 4 males and 11 females, aging 53-68 years. Isthmic defects were located
      at L4 in 9 cases, at L5 in 6 cases. Four patients were smokers. The preoperative
      mean disc space height was 5.4 +/- 2.3 mm, the mean percentage of slip was 36.8%
      +/- 7.2%. In group B, 12 patients were treated by PLIF using autogenous bone
      grafting and cage fusion with pedicle screw fixation, including 3 males and 9
      females, aging 56 years. Isthmic defects were located at L4 in 8 cases, at L5 in
      4 cases. Five patients were smokers. The preoperative mean disc space height was
      5.7 +/- 2.5 mm, the mean percentage of slip was 37.8% +/- 6.2%. Two groups were
      compared in the amount of blood loss, duration of hospitalization, back pain,
      radiating pain, fusion rate, the intervertebral disc space height, the
      postoperative degree of slip and the fusion rate. RESULTS: All patients were
      followed up for 24-38 months. The mean follow-up was 29 (24-36) months in group A
      and 26 (24-38) months in group B. There were no statistically significant
      differences in follow-up period, age, sex, the location of isthmic defects,
      smoking, the preoperative disc space height and the percentage of slip between
      two groups (P > 0.05). There were no statistically significant differences in the
      amount of blood loss, the duration of hospitalization, the fusion time between
      two groups (P > 0.05). But there were statistically significant differences in
      the back pain score, the radiating pain score and the fusion rate between two
      groups (P < 0.05). The postoperative disc space height and the degree of slip of
      the last follow-up were 5.8 +/- 2.2 mm and 25.6% +/- 7.2% in group A, 6.2 +/- 2.5
      mm and 24.1% +/- 7.4 % in group B, showing statistically significant difference
      (P < 0.05). CONCLUSION: The PLIF using autogenous bone grafting and cage fusion
      with pedicle screw fixations is more beneficial to improving the fusion rate and
      preventing longterm instabilities than simple cage alone fusion with pedicle
      screw fixation in adult spondylolisthesis.

PMID- 16892812
TI  - [Effect of sodium hyaluronate on proliferation and differentiation of myoblast in
      vitro].
AB  - OBJECTIVE: To investigate the effects of sodium hyaluronate solution on the
      proliferation and differentiation of myoblasts. METHODS: The 3rd subculture
      myoblasts from muscle of infant SD rat were cultured in four growth media, in
      which the concentrations of sodium hyaluronate were 0.05% (group A), 0.1% ( group
      B), 0.2% (group C)and 0 (group D, control group), respectively. The proliferation
      rate of myoblasts in each medium was observed through growth curves by means of
      count and MTT. At the same time, the subculture myoblasts were cultured in
      differentiated media in which the concentrations of sodium hyaluronate were 0 and
      0.1%. The capacity of fusion of myoblasts was compared between two kinds of
      differentiated media. RESULTS: There were the nearly same proliferation curse in
      Groups A, B and C: increasing by logarithm at 2 days and reaching peak value at 4
      days. The myoblasts in Group D increased slowly: increasing by logarithm at 3
      days, doubling at 5 days and reaching peak value at 6 days. MTT has the similar
      curse to counting. The myoblast proliferation of Group B was more than that of
      the other groups. The peak value of myoblast fusion was 35% at 6 days in common
      differentiated media; slowly reached 11.7% at 7 days in the differentiated media
      in which the concentrations of sodium hyaluronate was 0.1%. CONCLUSION: Sodium
      hyaluronate at certain concentration can be a decent media for myoblasts, it can
      accelerate proliferation and differentiation of myoblasts.

PMID- 16892813
TI  - [Effects of conditioned medium derived from keratinocytes on fibroblasts].
AB  - OBJECTIVE: To observe the effects of keratinocytes on proliferation and collagen
      secretion of fibroblasts. METHODS: The conditioned medium, collected from
      cultured keratinocytes, was added to the cultured fibroblasts as the tested
      groups (12.5%, 25% and 50% groups) and DMEM as control group. The MTT,
      hydroxyproline colorimetric method and flow cytometer were employed to measure
      the fibroblast proliferation, the collagen secretion and the change of the cell
      cycle. RESULTS: In fibroblast proliferation, the absorbency(A) value of tested
      groups was significantly different from that of the control group (P<0.01). A
      value increased as increasing concentration, there was statistically significant
      difference between the concentrations of 25%, 50% and the concentration of 12.5%
      (P<0.01), but no statistically significant difference between the concentrations
      of 25% and 50% (P>0.01). In collagen secretion, there was no statistically
      significant difference between the tested groups and the control group(P>0. 01),
      and between the tested groups(P>0.01). In cell cycle, 50% of conditioned medium
      could make the fibroblast pass the limit of G1/S and S/G2 period, the cell rates
      of S,G2-M period increased. CONCLUSION: The conditioned medium from keratinocytes
      can increase fibroblasts proliferation, have little effect on general collagen
      secretion.

PMID- 16892814
TI  - [Fast harvest of seed cells for composite tissue engineered skin at one time].
AB  - OBJECTIVE: To find a feasible method that can fast isolate seed cells,
      keratinocyte stem cell and fibroblasts, for composite tissue engineered skin.
      METHODS: The foreskin could be attained from posthectomy, the subcutaneous tissue
      was removed completely, and the full-thick skin was cut into pieces, 2 mm x 2 mm
      in size, then the pieces were submerged into a centrifuge tube containing
      collagenase I in a oscillator. After 3-hour digestion at 37 degrees C, the dermis
      was dissolved completely with all the fibroblasts in the digestion solution and
      the epidermis could be separated easily. With more than 10-minute digestion in
      trypsin at 37 degrees C, the epidermal cells could be harvested. Then
      flowcytometry and FITC-immunofluorescence for cytokeratin 19 of epidermal cells
      and FITC-immunofluorescence of vimentin of fibroblast were conducted to identify
      keratinocyte stem cells in the epidermal cells and fibroblasts in the digestion
      solution. Moreover, epidermal cells and fibroblasts were cultured in vitro for 7
      days to investigate their biological behavior. RESULTS: Using collagenase I
      combined with trypsin, epidermal cells and fibroblasts could be isolated at one
      time within 3 hours. Up to 17% cells demonstrated cytokeratin 19 positive in the
      epidermal cells, with fibroblast vimentin positive. The amount of fibroblast
      could be enlarged to more than 100 times within 6 days, but the putative
      keratinocyte stem cells were difficult for subculture. CONCLUSION: Seed cells for
      composite tissue engineered skin could be harvested fast at one time, that made
      it possible to reconstruct composite tissue-engineered skin in vitro.

PMID- 16892815
TI  - [Preparation of plastic nano-hydroxyapatite/poly (3-hydroxybutyrate
      hydroxyvalerate)-polymethyl lene glycol gentamicin drug delivery system].
AB  - OBJECTIVE: To develop the plastic nano-hydroxyapatite (nano-HA)/poly (3
      hydroxybutyrate-hydroxyvalerate)-polyethylene glycol (PHBV-PEG) gentamicin (GM)
      drug delivery system (DDS) (nano-HA/PHBV-PEG-GM-DDS) for treating osteomyelitis
      and find its releasing character in vivo. METHODS: The plastic nano-HA/PHBV-PEG
      GM-DDS was prepared using nano-HA as the core carrier of GM, nano-HA with PHBV
      and PEG as coating and plastic fibrin glue(FG) as microsphere scaffold. The
      morphological features of nano-HA, drug loaded nano-HA and drug loaded nano
      HA/PHBV-PEG microsphere were examined by electron microscope. The GM
      concentration it blood, cortex bone and cancellous bone was detected at 12
      different time points by the method of K-B after the plastic nano-HA/PHBV-PEG-GM
      DDS was implanted into the femora of 36 rabbits. Its GM releasing character was
      assayed in vivo. RESULTS: Nano-HA was similar to a blackjack, and its length was
      less than 60 nm. Drug loaded nano-HA appeared natural crystal condensate, of
      which surface adsorbed massive GM. The average grain diameter was 200.5 nm. Drug
      loaded nano-HA/PHBV-PEG microsphere had a shrinkable porous structure, of which
      surface configuration was consistent. The average grain diameter was 34.5 microm.
      The GM concentration and the antibacterial annulus was in the linear correlation.
      The correlation coefficient was 0.998. In cortex and cancellous bone tissue, the
      GM concentration was about 95.50 +/- 16.50 microg/ml and 80.20 +/- 13.80
      microg/ml from the plastic nano-HA/PHBV-PEG-GM-DDS on the 1st day, then decreased
      gradually. After 56 days of operation, the GM concentration still exceeded the
      minimum inhibitory concentration for the staphylococcus aureus, but the peak
      level of serum GM concentration was under the nephrotoxicity concentration.
      CONCLUSION: Plastic nano-HA/PHBV-PEG-GM-DDS was a good drug delivery system with
      sustained antibiotic effect in vivo. It was an effective method for the treatment
      of osteomyelitis.

PMID- 16892816
TI  - [Research advance in prevention of postoperative adhesion using
      carboxymethylcellulose].
AB  - OBJECTIVE: To study the prevention of postoperative adhesion using
      carboxymethylcellulose (CMC). METHODS: The literature was reviewed extensively,
      concerning the physical and chemical characters of CMC, the mechanism of
      preventing adhesion, the effect on healing of anastomoses, the experimental
      researches and the clinical application. RESULTS: CMC was a polysaccharide with
      favorable biocompatibility, biodegradation, stable physical and chemical
      characters, and it can prevent postoperative adhesion. CONCLUSION: CMC is with a
      wide outlook in prevention of postoperative adhesion.

PMID- 16892817
TI  - [Aldosterone: basic physiopathology and new mechanisms of action in the distal
      nephron].

PMID- 16892818
TI  - [New evidences in renal transplantation bibliography].

PMID- 16892819
TI  - [Renal and pancreatic donation and transplantation activity in Spain 2005].

PMID- 16892820
TI  - [Ecographic study of kidney size in children].
AB  - OBJECTIVE: The objective of this study is the determination of the normal kidney
      size in children analysing the variables that have a good correlation with it.
      With these correlations the normal kidney size can be established and a diagnose
      of possible diseases set. METHODS: The data was obtained through ecographies
      taken in 474 children between 0 and 18 years old that were under control for
      several reasons differently from the suspicion of a kidney disease. The
      information related to age, sex, weight, height and corporal surface was also
      taken. RESULTS: We studied 265 girls and 209 boys. No difference was obtained
      between the size of the girls and boys kidneys. The regression analysis of the
      left kidney shows correlations of 0.911 for the height, 0.896 for the corporal
      surface, 0.863 for the weight and 0.857 for the age; while the one of the right
      kidney shows correlations of 0.921 for the height, 0.902 for the corporal
      surface, 0.872 for the age and 0.871 for the weight. The determination
      coefficients were 0.83 for the left kidney and 0.85 for the right one. The
      multivariant analysis shows that for both kidneys the height and the age are
      variables statistically significant as well as the corporal surface for the left
      kidney. CONCLUSIONS: The size parameters measured in the kidneys show a
      statistically significance correlation with certain parameters of the growing.
      The maximum correlation appears for the height of the patient, which allows
      establishing regression equations with the kidney size and the height and
      therefore to detect any deviations from these regression curve.

PMID- 16892822
TI  - [Evaluation of "hidden" renal insufficiency by abbreviated-MDRD equation].
AB  - BACKGROUND: Early detection of renal insufficiency (RI) allows to start therapies
      in order to slow renal disease progression and modify associated risk factors.
      Serum creatinine (Cr) is not a good marker of renal insufficiency. Some patients
      with significant renal failure can show Cr values in the normal range. Cr derived
      equations can help us to estimate glomerular filtration rate (GFR) more
      precisely. The aim of this study has been to know the utility of abbreviated-MDRD
      equation to detect "hidden" (non detected by Cr) renal insufficiency in patients
      attending general practices. MATERIAL AND METHODS: Patients with blood samples
      attending general practices in two localities were studied during one year. In
      all, one thousand patients were included. Collected data were: age, sex,
      creatinine, haemoglobin, previous diagnosis of arterial hypertension or diabetes
      mellitus and chronic abuse of analgesic. Abbreviated MDRD equation was used to
      know GFR. "Hidden" RI was defined when GFR was lower than 60 ml/min/1.73 m2 and
      Cr was in the normal range. RESULTS: 104 (10.4%) patients showed "hidden" RI.
      Patients with "hidden" RI were older (70.7 +/- 12.5 vs. 52.4 +/- 18.6 years, p <
      0.001), were more frequently women (86.5% vs 62.4%, p < 0.001) and hypertensive
      (46.1% vs. 23.6%, p < 0.001) and showed lower levels of haemoglobin (13.8 +/- 1.3
      vs 14.2 +/- 1.3 g/dl, p = 0.001). CONCLUSIONS: In patients attending general
      practices abbreviated-MDRD allows to recognise a significant number of patients
      with "hidden" renal insufficiency, but with normal range creatinine. Patientes
      with "hidden" renal insufficiency are more frequently older, women and
      hypertensive.

PMID- 16892821
TI  - [Renal function and cardiovascular risk in patients with essential hypertension.
      The "FRESHA" study].
AB  - BACKGROUND: In the past few years there has been a growing amount of information
      about renal dysfunction and cardiovascular risk. The objectives of this study
      were to assess the prevalence of renal dysfunction and evaluate the relation
      between renal function and cardiovascular risk in patients with essential
      hypertension. METHODS: A multicenter, cross-sectional survey of unselected
      patients with essential hypertension attending primary care settings in Spain was
      performed between june and november 2004. Renal function was evaluated with the
      abbreviated equation of the Modification of Diet in Renal Disease study. Renal
      insufficiency was defined as an estimated glomerular filtration rate <60
      ml/min/1.73 m2. RESULTS: Eighty-eight investigators from 50 centers recruited
      2130 patients being mean age 65.6 +/- 11 years and female 53%. Prevalence of
      diabetes, lipid abnormalities, and previous cardiovascular disease were 30.3%,
      45.9%, and 42.1% respectively. Prevalence of renal insufficiency was 32.4% (95%
      CI 30.4-34.4). Patients suffering from renal insufficiency showed a higher
      prevalence of cardiovascular disease when comparing with those with an estimated
      glomerular filtration rate = or >60 ml/min/1.73 m2 (56.2% vs. 35.3%, OR 2.35, 95%
      CI 1.95-2.82, p < 0.001). A logistic regression analysis showed that the relation
      of renal dysfunction with cardiovascular disease was independent of other
      variables or classical cardiovascular risk factors as age, female sex, diabetes,
      smoking, hypercholesterolemia, and systolic blood pressure. CONCLUSIONS: Renal
      insufficiency was present in 32.4% of patients with essential hypertension
      attending primary care settings. Cases with renal dysfunction showed a higher
      cardiovascular risk. Hypertensive patients with renal insufficiency should be
      considered as candidates for an aggressive approach of cardiovascular risk
      management.

PMID- 16892823
TI  - [Accuracy of indirect estimates of renal function in advanced chronic renal
      failure patients].
AB  - Cockcroft-Gault (CG) and Modification of Diet in Renal Disease (MDRD) formula are
      indirect estimates of renal function which have been widely accepted, though
      their accuracies have been scarcely validated in advanced chronic renal failure.
      The purpose of this study was to determine the accuracy (bias and precision) of
      these formulas in advanced CRF patients. The study group consisted of 99
      unselected patients (62 +/- 15 years, 59 females) with advanced CRF. The
      glomerular filtration rate (GFR) was measured by Tc(99m) DTPA. Simultaneously,
      estimates of GFR by CG corrected for 1.73 m2 and MDRD (formula 7) were
      calculated. Agreement was evaluated graphically, bias was assessed by mean and
      median difference, and precision by median absolute differences and Bland-Altman
      plots. Mean GFR by DTPA, CG and MDRD were: 16.24 +/- 4.38 and 16.77 +/- 4.65 and
      13.58 +/- 4.27 ml/min/1.73 m2, respectively. MDRD equation significantly
      underestimated GFR-DTPA (p = 0.0001). Both CG and MDRD correlated significantly
      with GFR-DTPA (R = 0.53 and R = 0.62, respectively). CG formula performed better
      than the MDRD equation with respect to bias (0.30 vs -3.24 ml/min/1.73 m2, p =
      0.0001), and precision (0.58 vs. -3.11 ml/min/1.73 m2, p = 0.0001). By multiple
      linear regression, the best determinants of the error of the estimation by CC
      formula were: serum creatinine (beta = -0.58; p < 0.0001), age (beta = -0.62; p <
      0.0001), and body mass index (beta = 0.26, p = 0.004), and by MDRD formula were:
      serum creatinine (beta = -0.38; p < 0.0001), and body mass index (beta = -0.20, p
      = 0.03). In conclusion, in unselected patients with advanced chronic renal
      failure, estimates by CC formula were more accurate than those obtained by MDRD
      formula. Serum creatinine was the main source of error of the estimation of GFR
      by both formulas, though demographic and anthropometric characteristics
      influenced as well on their accuracies.

PMID- 16892824
TI  - [CA-P control in haemodialysis and K/DOQI guidelines].
AB  - BACKGROUND: The publication in 2003 of the K/DOQI Clinical Practice Guidelines
      for Bone Metabolism and Disease in Chronic Kidney Disease recommended targets
      levels for serum iPTH, Ca, P, and CaxP product. However, many patients do not
      achieved these target ranges. It is necessary to known the percentage of patients
      out of range in order to prevent the development of bone disease and to reduce
      mortality and morbidity. OBJECTIVES: To know the degree of control of Ca-P
      metabolism in haemodialysis patients in our haemodilalysis facilities and the
      achievement of target levels recommended by K/DOQI Guidelines. PATIENTS AND
      METHODS: We have retrospectively investigated in 190 prevalent haemodialysis
      patients (males 58.2%, ratio M/F 1.4, mean age 70 years, range 17-87 years, at
      least 3 months in haemodialysis) the serum levels of Ca, albumin-corrected serum
      Ca, P, CaxP product and iPTH in all analitycal determinations performed in 2004.
      In each patient we have obtained the average (and median) of these serum markers.
      Cut-off levels were carried out following the recommendations of the K/DOQI
      Guidelines. RESULTS: The average of serum Ca and albumin-corrected serum Ca is
      normal (means +/- SD = 8.9 +/- 0.6 mg/dL and 9.2 +/- 0.7 mg/dL, respectively);
      however, 53.7% has normal values, 9.1% hypocalcemia and 37.1% hypercalcemia. The
      average of serum P is also normal (mean +/- SD = 5.0 +/- 1.3 mg/dL); however,
      only 57.2% has normal values, and 11.7% has hypophosphoremia and the remaining
      31, 1% hyperphosphoremia. The CaxP product is normal (mean +/- SD = 46.3 +/- 13.3
      mg2/mL2), 4.9% with low values and 23.4% with high values. The median of serum
      iPTH is 253 pg/mL, but only 31.1% of them have normal values, 25.1% low range
      values and 43.7% has hyperparathyroidism; 9.3% with iPTH higher than 800 pg/mL.
      The percentage of patients with hyperphosphoremia is higher in the group with
      iPTH higher than 300 pg/mL (23.3% vs. 40%, chi2, p= 0.006). In patients with PTHi
      in normal range, 3.6% have low CaxP product and the remaining 17.8% high CaxP
      product. Overall, only 25% of patients falls within recommended ranges for all
      indicators of mineral metabolism and 17% has all serum markers outside these
      recommendations. CONCLUSIONS: The degree of control of mineral metabolism in
      haemodyalisis patients if clearly insufficient and a large percentage of them do
      not achieved the recommended serum targets recommended by K/DOQI Guidelines. This
      groups of patients are exposed to a increased risk for oseous and cardiovascular
      morbimortality. The analysis of adequacy must be performed with percentage of
      patients out of range in order to apply new therapeutical strategies.

PMID- 16892825
TI  - [Estimation of the cost in the farmacologic treatment of chronic renal failure].
AB  - The prevalence and incidence of end stage renal disease has increased
      considerably in the past years. We know that the cost of treatment of these
      patients is high. Limited information exists on care resource utilization for
      maintenance of patients before the initiation of replacement therapy. The purpose
      of this study is determine the cost of pharmaceutic treatment during the
      predialysis phase. Pharmacy cost was analyzed for 200 patients controlled on
      outpatient nephrology department. The mean age was 72.4 years, 59% were males,
      and the comorbidity distribution was: hypertension 87%, hyperlipidemia 56% and
      diabetes 35%. The per-patient-per-month charges were 215.45 Euro, with a
      continous increase from 84.64 Euro on stage 1 to 352.59 Euro on stage 5 of
      chronic kidney disease. Erythropoiesis stimulants were reponsible of 46.5% of
      these cost. The most frequent prescribed medications were antihypertensive drugs,
      statins and iron preparations. Patients with end stage renal disease generate
      significant cost during the predialysis period. The limited resources, and the
      growth of health care expeditures, particulary the spending for prescriptions
      drugs, are two of the major problems for Health Care Systems. A better knowledge
      of the associated costs to the treatment of these patients will help us to
      increase our efficiency.

PMID- 16892827
TI  - [Treatment of acute lithium intoxication with high-flux haemodialysis membranes].
AB  - Lithium carbonate is commonly prescribed for the treatment of bipolar (manic
      depressive) disorders. However, because of its narrow therapeutic index an
      excessive elevation of serum lithium concentration, either during chronic
      maintenance therapy or after an acute overdose, can result in serious toxicity.
      In addition to supportive care, the established treatment of severe lithium
      toxicity is haemodialysis. Conventional haemodialysis can reduce serum lithium
      rapidly, but post-dialysis rebound elevations with recurrent toxicity have been
      documented in old publications. High-flux membranes should be capable of removing
      more lithium per hour of haemodialysis, but published values are not available.
      We report here three patients with acute lithium intoxication who were treated
      successfully with bicarbonate and high-flux haemodialysis membranes. Our patients
      presented with a severe degree of intoxication, based on the amount of drug
      ingested, the initial serum lithium level, the severity of neurologic symptoms
      and systemic manifestations. Two patients developed acute renal failure probably
      as a result of volume depletion since it was rapidly reversible by haemodialysis
      and infusion therapy. In addition, consecutive haemodialysis sessions and
      improvement of renal function allowed a rapid decrease in serum lithium levels
      without haemodynamic instability or rebound elevations in lithium concentration.
      The effectiveness of the procedure in these cases can be attributed to the use of
      bicarbonate dialysate and high-efficiency dialysers. This is the first report
      describing the effect of high-efficiency dialysers on lithium pharmacokinetic.
      Using this technique the elimination rate of lithium was found to be greater than
      previously reported with haemodialysis.

PMID- 16892826
TI  - [Telemedicine and follow up of peritoneal dialysis patients].
AB  - Mean-term experience in the use of Telemedicine in Peritoneal Dialisis (PD)
      patients is limited as well as its cost-benefit. The main objective of this work
      is to evaluate Telemedicine utility in mean-long term control of stable PD
      patients, analyzing if the televisit (TV) could substitute 50% of the programed
      inhospital consults (HC) the time spent in both visit modalities, the quality of
      patient-personel contact as well as how image and sound have been perceived.
      Visit resolution was analyzed taking into account the need of HC after a TV; We
      also have studied if it would be possible to retrain patients in the dialisis
      technique with telemedicine, and we have checked the patient perceived quality
      and calculate the real and social costs. METHODS: during 18 months, the system
      has been implanted to 19 patients with 7 +/- 4 follow up (range 3-17). A Falcon
      videoconference kit at patient's place was used, connected to the home television
      set. In the hospital there was a computer with a videoconference card, webcam and
      software meeting point which permits the control of patient's camera from the
      hospital. Both are connected by a 3RDSI line system. A monthly programmed HC or
      TV has been made. If more controls had been required, they have been made by TV
      Time spent was recorded on each TV and patients and staff questionary were
      inquired. RESULTS: (a) PATIENTS: mean age 44 +/- 8 years, 13 (68%) male. 12 (63%)
      had elemental educational level and 7 (37%) mean-superior. 17 (89%) were actively
      working. The PD technique was: CAPD 6 (32%) and APD13 (68%). (b) Televisits: 103
      TV have been made. 22 +/- 9 minutes were spent on each TV less than in the HC, 33
      +/- 8 minutes (p < 0.01). There were technical problems related with lines in 21
      TV, but only in 4 the connection was not possible. 92 TV (89%) were made on time,
      99 (96%) had a good image quality and 96 (93%) had a correct sound. 100% of
      patients perceived TV as close to HC. In 90 TV (87%) medical treatment was
      modified. Only in 4 cases (3.9%) patients needed an hospital visit. According to
      patient's valuation, TV replaced correctly to HC in 97 instances (94%) and in 97
      (97%) in staff opinion. In all cases (100%) catheter exit site could be evaluated
      as well as edema presence. Retraining was possible in all cases. There was a save
      in nurse's time and patient's time and also, a save in physical hospital space.
      Initial investment apart, the daily cost increment was scarce (1.5 Euro) taking
      into account that there is a save in time for patients and personnel, save in
      physical space in hospital and in sanitary transport. CONCLUSION: Telemedicine is
      useful from the clinical point of view in the mean-term for stable patients in
      PD. Daily cost increment is scarce and there is a save in time for patients and
      personnel, save in physical space in hospital and in sanitary transport.

PMID- 16892828
TI  - [The start of dialysis treatment in a Spanish department].

PMID- 16892829
TI  - [Preclinical diagnosis of the familial nephropathy associated to hyperuricemia].
AB  - We describe one patient with the pre-symptomatic diagnosis of the disease named
      afamilial nephropathy associated to hyperuricemia)) (OMIM 162000; FJHN). This is
      a hereditary disease, autosomic dominant, characterized by its progression to
      renal insufficiency. Several mutations in the gene that codifies uromodulin or
      Tannn-Horsfall protein (UMOD) have been identified in some families. The clinical
      presentation is heterogeneous. In some cases the disease appears as juvenile
      hyperuricemia due to a diminished renal urate excretion, with or without gout,
      but in some other cases the first manifestation is renal insuffciency. The study
      of the UMOD gene shows that patient is heterozygous for the mutation C869 --> A,
      which results in C255Y change, and enabled to establish the diagnosis of FJHN.
      This patient shows the possibility to identify the genetic alteration associated
      to FJHN in early stages. This fact implies a clinical follow-up and eventual
      treatment to reduce the inexorable progression to renal insuffciency.

PMID- 16892830
TI  - [Peritoneal implants in patients affected by chronic renal failure in
      hemodialysis programme].
AB  - The presence of peritoneal implants detected by computered axial tomography (CT)
      is usually related to mesothelial primary neoformative processes or, more
      frequently to peritoneal metastasis or peritoneal carcinomatosis. Although the
      higher prevalence of neoplastic processes in the chronic renal failure
      population, the association of peritoneal implants and constitutional syndrome is
      not always correlated to peritoneal carcinomatosis. We present the case of two
      patients with chronic renal failure in hemodialysis programme, with abdominal
      insidious clinical, constitutional syndrome and similar peritoneal implants seen
      by CAT: the histologic analysis of peritoneal implants gave the definitive
      diagnostic of secondary amyloidosis and peritoneal tuberculosis respectively.

PMID- 16892831
TI  - [Opinion survey on living kidney donors].

PMID- 16892832
TI  - [Impactation of permanent tunneled catheter for hemodialysis in the jugular vein,
      an exceptional complication].

PMID- 16892833
TI  - [Acute renal failure after attempted suicide with cyanide and mercury salts.
      Report of a case].

PMID- 16892834
TI  - [Rapidly progressive multipathogenic glomerulonephritis].

PMID- 16892835
TI  - [It is necessary to develop the nephrologic consultation out of the hospital].

PMID- 16892836
TI  - [Severe asymptomatic mixed alkalosis in a female patient during hemodialysis].

PMID- 16892837
TI  - Dendritic cell biology, dysfunction and immunotherapy in gastrointestinal
      cancers.
AB  - Gastrointestinal (GI) cancers make up a significant proportion of newly diagnosed
      malignant disease. The five-year survival for these GI cancers is poor. Anti
      cancer host defences are thought to play a role in these cancers, albeit they are
      suboptimal. Novel immunotherapies are being introduced to treat such patients.
      This review describes basic cell biology of dendritic cells, as they are
      thoughtto play a key role in generating effective anti-tumour responses.
      Dendritic cell dysfunction in patients with various cancers is documented and
      immunotherapy using dendritic cells in a range of GI cancers is described and
      discussed

PMID- 16892838
TI  - Neoadjuvant chemotherapy in women with large and locally advanced breast cancer:
      chemoresistance and prediction of response to drug therapy.
AB  - Patients with large and locally advanced breast cancer (LLABC) present with a
      therapeutic challenge and undergo multimodality treatment. Many such patients
      receive neoadjuvant chemotherapy (NAC) prior to surgery. However, a number of
      these patients do not respond well to NAC and only a percentage (usually less
      than 30%) obtains a complete or optimal response. A range of mechanisms are
      believed to be involved in this chemoresistance, including ATP binding cassette
      (ABC) transporter overexpression, dysregulation of apoptosis and possibly
      increased numbers of cancer stem cells. The chemoresistant processes may be due
      to more than one mechanism. The ability to predict a response to NAC would be
      beneficial, targeting expensive and toxic drug treatment to those likely to
      respond and providing a therapeutic strategy for further post-operative
      chemotherapy. Currently, many biomarkers have been studied with a view to
      establishing a predictor of response. However, no single biomarker appears to be
      effective. Genomics is a novel biotechnological process which is being used to
      predict response to drug therapy; this work is currently at an early stage of
      development

PMID- 16892839
TI  - Laryngopharyngeal reflux: A literature review.
AB  - Laryngopharyngeal reflux (LPR) is a common condition encountered in
      otolaryngological practice in the United Kingdom. It is one of the most important
      aetiological factors for many inflammatory disorders of the upper aerodigestive
      tract. The presentations are diverse and include chronic hoarseness, sensation of
      a foreign body in the throat, sore throat, dysphagia, postnasal drip, excessive
      throat mucous, chronic cough and throat clearing. LPR patients may not complain
      of heartburn. Although LPR is common, its diagnosis may not be easy, as its
      symptoms are non specific and the laryngeal findings are not always associated
      with symptom severity. This article discusses an overall view of LPR in terms of
      pathophysiology, clinical presentation, diagnosis and treatment

PMID- 16892840
TI  - Jass staging is a predictor of outcome following "curative" resection of Dukes' B
      colorectal carcinoma.
AB  - BACKGROUND AND AIMS: We have sought to determine if the addition of the Jass
      pathological classification to Dukes' staging would provide improved prognostic
      information for patients undergoing curative surgery for Dukes' B colorectal
      carcinoma. PATIENTS AND METHODS: One hundred and eighty three patients who
      underwent curative surgery for Dukes' B colorectal cancers between December 1988
      and January 1998 were identified. An assessment of Jass scoring was made at the
      time of initial histological staging. All patients entered a comprehensive follow
      up system. RESULTS: Jass grouping was found to correlate significantly with
      cancer specific mortality rates; group III having a worse prognosis than groups I
      and II (p<0.005). There was no significant difference between either local
      recurrence or systemic recurrence and the Jass group. CONCLUSION: The Jass
      classification provides additional prognostic information in patients following
      curative resection of Dukes' B colorectal carcinoma and may therefore facilitate
      the selection of patients who will benefit most from adjuvant treatment

PMID- 16892841
TI  - Review of photodynamic therapy.
AB  - INTRODUCTION: Photodynamic Therapy (PDT) is an emerging treatment for a variety
      of conditions including ocular and extra ocular diseases. The porphyrins have
      been used extensively, as dyes, which are laser-activated to achieve desired
      clinical effects. Commonly used agents are verteporfin and porfimer sodium.
      METHODS: We performed a literature search of the PubMed database using the
      medical search headings: photodynamic therapy, photosensitizer verteporfin,
      visudyne, porfimer sodium and photofrin. We also performed a manual search using
      references from these articles, review articles and manufacturers' product
      monographs. RESULTS: Verteporfin and porfimer sodium are commonly used
      photosensitizing agents with their wide applications in different fields of
      medicine. Both have well established safety profiles. They are most commonly used
      in wet age-related macular degeneration, gastrointestinal diseases and bronchial
      cancers. CONCLUSION: PDT is a well established treatment entity in ophthalmology
      and other medical fields. In ophthalmology, it has rekindled interest and hopes
      in the common yet sight-threatening problem of age-related macular degeneration
      (AMD). This problem is still considered to be a serious issue as far as
      management is concerned. However in selective cases of AMD, it has shown success
      in restoring sight, especially in the 'classic' form of the disease. PDT is also
      being used to treat a range of solid cancers and non malignant conditions

PMID- 16892842
TI  - Not all pain in the left iliac fossa is diverticular disease: A case study of a
      psoas myxoma and review.
AB  - Intramuscular myxomas are rare, benign, mesenchymal tumours that may present to a
      wide variety of specialties. We present a case study of an intramuscular myxoma
      in the psoas muscle, followed by a review of the literature regarding the
      diagnosis and treatment of intramuscular myxomas

PMID- 16892843
TI  - Renal artery aneurysm treated with ex vivo repair and autotransplantation.
AB  - Renal artery aneurysms are being encountered more frequently due to a wider use
      of angiography. As the risk of rupture is unclear, the indications for surgery
      remain controversial. Despite advances in treatment, complex aneurysms often
      require nephrectomy for adequate excision. We report a case of an incidentally
      diagnosed renal artery aneurysm successfully treated with extracorporeal repair
      and autotransplantation. Ex vivo repair and renal autotransplantation is a safe
      and effective treatment for the management of complex renal artery aneurysms

PMID- 16892844
TI  - Re: Baskett T.F. Edinburgh connections in a painful world. Surgeon 2005; 3(2): 99
      107.

PMID- 16892845
TI  - Re: Wheatley DJ. The future role of surgery in ischaemic heart disease. Surgeon
      2005; 3(3): 150-58.

PMID- 16892846
TI  - Re: Downes M, Mohan P, Little D, Hickey D. Pancreas transplantation in Ireland.
      Surgeon 2005; 3(1):17-20.

PMID- 16892847
TI  - Re: Langer's axillary arch: Anatomy, embryological features and surgical
      implications. Surgeon 2005;3(5):325-27.

PMID- 16892848
TI  - [Chromatin diminution at the border of the XX and XXI centuries].
AB  - The size of genomes in eukaryotic organisms is one of the greatest mysteries of
      biology. As known from the middle of the XX century, the level of organization of
      a particular organism, does not depend on its genome size, i. e. on DNA amount in
      the nucleus. We believe that an actual function of non-coding DNA stands behind
      the phenomenon of chromatin diminution, known already for 100 years. Diminution
      of chromatin normally takes place in cells involved in body building and never
      occurs in developmental precursors of germ cells. Apparently, the former are
      cells, in which non-coding DNA is functionally significant. We cloned a fraction
      of DNA eliminated during chromatin diminution of Cyclops kolensis (Cyclopoida,
      Crustascea) and sequenced 90 clones totally making 32 kb. Taken together, the
      provided evidence has demonstrated a high organization ordering of DNA sequences
      restricted to the germ line. Chromatin diminution never takes place in human
      cells and in cells of the majority of animals. These cells may isolate non-coding
      DNA in other ways, making it unreactable for most enzymes and thus functionally
      cut off. Thus, a certain part of genome with a particular size and structure may
      serve for genetic isolation of species as shellfish or junk DNA are vital
      components rather than pieces of garbage.

PMID- 16892849
TI  - [Dynamics of morphofunctional organization and developmental potential of mouse
      embryos in the state of "two-cell block in vitro"].
AB  - Vital observation in combination with electron microscopy and immunocytochemistry
      was used for studying structural organization and developmental potential of
      BALB/c mouse embryos after cleavage cessation at a two cell stage caused by the
      "two-cell block in vitro" phenomenon. Modification of structure and viability of
      embryos was followed for 2 days from the time of cleavage arrest. Several hours
      before cleavage arrest, changes in mitochondrian distribution were noticed in
      embryos, no other disturbances in structural organization of blastomeres being
      obvious. Embryos, whose development was arrested for 24 h, remained viable and
      demonstrated some morphological changes similar to those seen in normally
      developing embryos of the same age. Towards the end of a 48 h block period some
      embryos died, the surviving embryos remained morphologically intact and
      metabolically active. At the same time, the nuclei of the latter frequently
      displayed chromatin condensation near the nuclear membrane, which is similar to
      the pattern of chromatin reorganization in the nuclei of early apoptotic cells.
      Our results support a concept on the "two-cell block in vitro" phenomenon as a
      specific functional state of embryos, and well compare with data on a partial
      realization by blocked embryos of the developmental program.

PMID- 16892850
TI  - [Participation of bone-marrow stem cells in the differentiation of mdx mice
      striated muscle].
AB  - Two sets of experiments were carried out. The first one involved chimeric mice,
      obtained by intravenously injections of bone marrow derived cells taken from
      transgenic C57BL/6 mice, expressing GFP, to 5 Gy X-ray irradiated mdx or C57BL/6
      mice. In 2 months M. quadriceps femoris of chimeric mice were destroyed by
      surgical clamp. Following the next 4-5 weeks, the same muscles were studied for
      the presence of GFP-positive striated muscle fibres. In the case of chimeric
      C57BL/6 mice GFP-positive striated muscle fibres were observed in 0.3 +/- 0.5 and
      in 0.2 +/- 0.3 % of destroyed muscle, and in lateral (control) muscle,
      consequently. In the case of chimeric mdx mice, positive results were observed in
      1.7 +/- 0.4 and in 0.5 +/- 0.3 % of destroyed and control muscles, respectively.
      In the second set of experiments, the GFP-positive bone marrow cells were used
      for multiple intramuscular injections to M. quadriceps femoris of C57BL/6 or mdx
      mice in a dose of 2 x 10(5)-5 x 10(5) cells per mouse. Before injection, GFP
      positive bone marrow cells were fractionated in a 63 % Percoll solution and then
      were exhausted from differentiated cells by magnetic manner using CD4, CD8, CD38,
      CD45R, CD119, Ly-6G, and F4/80 antibodies. After 2-3 weeks, as many as 0.15 +/-
      0.40 and 0.1 +/- 0.2 % of GFP-positive muscle fibres were found in injected and
      control muscles of C57BL/6 mice, respectively. In the case of mdx mice, the
      frequency of GFP-positive striated muscle fibres was 2.0 +/- 0.8 and 1.2 +/- 0.6
      % for injected and control muscles, respectively. A conclusion is made that bone
      marrow stem cells can take part in differentiation of mdx mouse muscles after
      their delivery by needle injections.

PMID- 16892851
TI  - [Dynamics of microtubular cytoskeleton in higher plant meiosis. IX. The cycle
      accomplishment. Transition from phragmoplast to radial microtubule system].
AB  - In this study we analysed the terminal step of cytoskeleton cycle in higher plant
      meiosis: transition from phragmoplast to radial interphase configuration. Wild
      type meiosis in a range of mono- and dicotyledonous species was studied. A number
      of cytoskeleton abnormalities on this stage was described in meiotic mutants,
      haploids and wide hybrids of various species. We described processes of
      cytoskeleton rearrangements on this stage: disjunction of phragmoplast MTs, their
      shortening and the role of daughter cell membranes. The independence of the
      interphase radial MT system formation from the previous steps of cytoskeleton
      cycle and from nuclear envelope cycle is proposed.

PMID- 16892852
TI  - [Dynamics of microtubular cytoskeleton in higher plant meiosis. X. General scheme
      of cytoskeletal cycle].
AB  - An overview of a set of our previous papers titled "Dynamics of microtubular
      cytoskeleton in higher plant meiosis" is presented, in addition to some data on
      subcellular mechanisms underlying cytoskeleton reorganization during meiotic
      division in pollen mother cells. An illustrated scheme of cytoskeleton
      rearrangements during plant meiosis, both with successive and simultaneous
      cytokinesis, is given.

PMID- 16892853
TI  - [N-acetylcysteine reduces transformed 3T3-SV40 fibroblast sensitivity to lysis by
      natural killer cells].
AB  - We have shown that 18-20 h cultivation of transformed mouse fibroblasts 3T3-SV40
      in the presence of antioxidant, N-acetylcysteine (NAC, 10 mM), did not change
      their sensitivity to lysis by natural killer (NK) mouse splenocytes. However, in
      18-20 h after NAC removal 3T3-SV40 cells demonstrated resistance to NK cell
      activity. The cytotoxicity index (CI) was reduced up to 4.6 +/- 2.4 % (in
      comparison with the control value 31.8 +/- 2.4 %) approximating to the value in
      non-transformed 3T3 mouse fibroblasts. Normal 3T3 cells were resistant to NK
      action in all experimental conditions (CI varied within 0.7-5.3 %). These results
      show that NAC can induce partial reversion of transformed phenotype. We suggest
      that this effect may be due to the NAC-induced modifications of the cell surface
      and extracellular matrix proteins.

PMID- 16892854
TI  - [Investigation of properties of the thermostable protein complex obtained from
      the myocardium left ventricles of adult white rats].
AB  - A thermostable protein complex (TSPC) obtained from the myocardium ventricules of
      adult rats inhibits mitotic and transcriptional activity of cardiomyocytes. At
      the same time this complex is more active on early stages of the postnatal
      ontogenesis in rats, aged 1 and 5 days. Following its action on RNA synthesis,
      the TSPC reveals tissue specificity only in cells with terminal differentiation,
      and is determined by its nuclear membranes. We continue studies for identifying
      the molecular weight and chemical nature of the TSPC, and the role of its
      different fractions in regulation of proliferation processes. Besides, it is
      planned to produce antibodies against TSPC fractions with the purpose to block
      its inhibitory effect on myocyte regeneration in the damaged myocardium.

PMID- 16892855
TI  - [Comparative study of molecular mechanisms of natural and synthetic polycationic
      peptides action on the activity of the adenylyl cyclase signaling system].
AB  - The molecular mechanisms of action of natural and synthetic polycationic
      peptides, forming amphiphilic helices, on the heterotrimeric G-proteins and
      enzyme adenylyl cyclase (AC), components of hormone-sensitive AC system, were
      studied. It is shown that synthetic peptides C-epsilonAhx-WKK(C10)-KKK(C10)
      KKKK(C10)-YKK(C10)-KK (peptide I) and (GRGDSGRKKRRQRRRPPQ)2-K-epsilonAhx
      C(Acm)(peptide II) in dose-dependent manner stimulate the basal AC activity,
      inhibit forskolin-stimulated AC activity and decrease both stimulating and
      inhibiting AC effects of the hormones in the tissues (brain striatum, heart
      muscle) of rat and in smooth muscles of the mollusc Anodonta cygnea. AC effects
      of these peptides are decreased after membrane treatment by cholera and pertussis
      toxins and are inhibited in the presence of the peptides, corresponding to C
      terminal regions 385-394 alphas- and 346-355 alphai2-subunits of G-proteins.
      These data give evidence that the peptides I and II act on the signaling pathways
      which are realized through Gs- and Gi-proteins. At the same time, natural
      polycationic peptide mastoparan acts on AC system through Gi-proteins and blocks
      hormonal signals mediated via Gi-proteins only. Consequently, the action of
      mastoparan on G-proteins is selective and differs from the action of the
      synthetic peptides. It is also shown that peptide II, with branched structure,
      directly interacts not only with G-proteins (less effective in comparison with
      peptide I with hydrophobic radicals and mastoparan), but also with enzyme AC, the
      catalytic component of AC system. On the basis of data obtained the following
      conclusions were made: 1) the formation of amphiphilic helices is not enough for
      selective activation of G-protein by polycationic peptides, and 2) the primary
      structure of the peptides, the distribution of positive charged amino acids and
      hydrophobic radicals in them are very important for selective interaction between
      polycationic peptides and G-proteins.

PMID- 16892856
TI  - An investigation of the factors influencing the choice of infant feeding methods
      among urban Zimbabwean women in the context of HIV transmission.
AB  - OBJECTIVE: To determine the socio-economic and cultural factors influencing the
      choice of infant feeding methods in urban Zimbabwe women in the context of HIV
      transmission. STUDY DESIGN: A prospective survey. SETTING: Clinics in Harare and
      Chitungwiza, Zimbabwe. SUBJECTS: A total of 200 women attending eight baby
      clinics, with babies aged up to two years. MAIN OUTCOME MEASURES: Infant feeding
      methods used by mothers, number of women who had undergone HIV testing, those who
      knew the link between HIV and breast feeding, and those who were afraid to breast
      feed. The most common reasons for breast feeding and formula feeding. RESULTS:
      Husbands had a greater influence on feeding practices than nurses, implying that
      social influences have a higher influence than the advice of medical personnel
      when choosing a method of feeding (58% and 42% respectively). Thirty three
      percent and 77% of women in Harare and Chitungwiza respectively knew the link
      between HIV and breast milk. Thirteen percent and 36% of the women were afraid to
      breast feed in Harare and Chitungwiza respectively. CONCLUSION: The level of
      education and employment status as well as the opinions of family members and
      health care personnel are the major factors that influence the choice of method
      of infant feeding. The multiplicity of factors complicate the decision making
      process, considering the benefits of breast feeding, which have to be weighed
      against the risk of transmitting HIV to the infant.

PMID- 16892857
TI  - Prevalence of asymptomatic malaria among school children in an urban and rural
      area in the Mount Cameroon region.
AB  - OBJECTIVE: To assess the prevalence of asymptomatic malaria among school children
      in an urban and a rural area during different seasons. SETTING: Molyko (urban
      area) and Bova (rural area), South West Province, Cameroon. SUBJECTS: 166 and 158
      randomly selected children in Molyko during the dry and rainy seasons
      respectively and 122 and 117 children in Bova during the respective seasons.
      DESIGN: A cross sectional study. MAIN OUTCOME MEASURES: Prevalence and parasite
      density of asymptomatic malaria in the urban and rural areas in the dry and rainy
      seasons. Prevalence of anaemia in infected and uninfected children during both
      seasons in the two areas. RESULTS: There was a significant association between
      axillary temperature and malaria parasitaemia in both seasons (p<0.05). Overall,
      the prevalence of asymptomatic malaria in the urban area (Molyko) was higher than
      that in the rural area (Bova) during both seasons, although the differences were
      not statistically significant (p>0.05). During the dry season, the prevalence of
      asymptomatic malaria in the urban area was 42.17% while that of the rural area
      was 40.16%. During the rainy season, the prevalence value in the urban area was
      46.20% and that in the rural area was 43.59%. Malaria infection rates decreased
      with age during both seasons in both areas and the difference between age groups
      was statistically significant in Molyko during the rainy season (p<0.05), and
      Bova during the dry season (p<0.05). Mean packed cell volume (PCV) levels were
      lower in infected than in uninfected children in all age groups and the
      difference was significant in Molyko during the rainy season and Bova during the
      dry season. CONCLUSION: The lack of a significant difference between the two
      seasons implies perennial transmission of the disease in the areas. Control
      measures are, therefore, urgently needed in this region to reduce the burden of
      the disease.

PMID- 16892858
TI  - Vitamin A status of term and preterm infants delivered at Harare Central Hospital
      and fed exclusively on breast milk.
AB  - OBJECTIVE: To investigate the vitamin A status of pregnant mothers, lactating
      mothers, preterm and term infants who were being fed exclusively on breast milk.
      DESIGN: Systematic/cross sectional. SETTING: Vitamin A research laboratory,
      animal science research laboratory, University of Zimbabwe, and Harare Central
      Hospital. SUBJECTS: 105 pregnant mothers attending the antenatal clinic at Harare
      Central Hospital for a routine check up were recruited for the study. Two groups
      of infants: those born at term and those with gestational age < or = 36 weeks.
      MAIN OUTCOME MEASURES: Serum retinol levels of infants/mothers pairs. Breast milk
      retinol levels. RESULT: The serum retinol levels for the infants were similar
      irrespective of age with a mean of 26.15 +/- 9.78 microg/dl. There was no
      statistically significant difference. The mean serum retinol levels of infants
      and mothers were significantly different, (p = 0.001). With mother/infant ratio
      of serum retinol concentration of 1.7:1. Maternal serum retinol levels correlated
      positively with infant serum retinol levels, r = 0.728. Forty four percent of the
      preterm and 17% of the term infants had serum retinol levels < 20 microg/dl,
      indicating deficiency, 2 and only 20% of the infants had retinol levels > 40
      microg/dl. CONCLUSION: The majority of infants might be at risk of vitamin A
      deficiency. Increased intake of vitamin A in pregnant women is necessary, and
      direct vitamin A supplementation of infants should be considered.

PMID- 16892859
TI  - Hypertension and diabetes mellitus: the critical role of evidence based decision
      making in patient management.
AB  - Many diabetic hypertensives are inadequately managed because of the doctor's
      misplaced emphasis on possible differences in efficacy and risk profile of
      antihypertensive drugs. These patients are at higher risk of various
      cardiovascular events, and evidence shows they experience greater reduction in
      adverse clinical outcomes as a result of tight control of blood pressure than do
      nondiabetic hypertensives. It is, therefore, critically important that such
      patients be identified and that the blood pressure is tightly treated. Several
      drugs often have to be used in combination in order to achieve adequate blood
      pressure control. Nonpharmacologic measures, such as exercise, have been shown to
      reduce blood pressure and to reduce the rate complications in diabetic patients.
      All classes of antihypertensives have been shown to be equivalent in reducing all
      adverse cardiovascular events in diabetic hypertensives. Although there is
      nothing to choose between diuretics, calcium channel blockers, beta-blockers,
      angiotensin converting enzyme inhibitors and angiotensin receptor blockers, the
      choice of drug should be tailored for the individual patient. Drug selection
      should be based on the complication that is most likely in the given patient.
      Available data suggests that the lower the blood pressure the better the
      prognoses, with no threshold of the lower limit of the ideal value. Many
      professional associations advise that a target blood pressure in the diabetic
      hypertensive under treatment should be below 130/80 mm Hg. There is no evidence
      to support the avoidance of thiazide diuretics in these patients, and indeed some
      patients derive specific benefits from the use of these drugs. Tight control of
      blood pressure is the overriding priority, and this takes precedence over the
      theoretical debate of which drug is the best choice or concern over possible
      adverse reactions.

PMID- 16892860
TI  - What do JCAHO surveyors look for in assessing the Universal Protocol?

PMID- 16892861
TI  - Could hospitals go the way of the airlines?

PMID- 16892862
TI  - Ensuring consistent time-out in a system.

PMID- 16892863
TI  - OR briefings aim to aid communication.

PMID- 16892864
TI  - Tracking supply charges with bar coding.

PMID- 16892865
TI  - Using computer's data to guide OR QI.

PMID- 16892866
TI  - Avoiding confrontation affects productivity.

PMID- 16892867
TI  - Ten tips for purchasing new technology.

PMID- 16892868
TI  - Tips for enforcing patient escort policies.

PMID- 16892869
TI  - Being prepared for emergency transfers.

PMID- 16892870
TI  - The new political advocacy.
AB  - Campaigning for support for the bottom line is giving way to trustees' mission to
      demonstrate hospitals' ongoing community benefit work to legislators.

PMID- 16892871
TI  - Standardizing safety.
AB  - A 25-year-old aviation safety tool, crew resource management (CRM), is
      dramatically improving patient safety in a growing number of hospitals.

PMID- 16892872
TI  - Keeping the relationship alive.
AB  - Hospitals will always need physicians, but to keep the connection alive, leaders
      must seek out their hospitals' physician champions.

PMID- 16892873
TI  - The board's role in strategic planning.

PMID- 16892874
TI  - The IT professional and change leadership.

PMID- 16892875
TI  - Mission possible: a financial assistance policy.
AB  - Finance: Alegent Health in Omaha, Neb., has crafted a financial assistance policy
      designed to provide care for all patients and protect them from financial
      hardship.

PMID- 16892876
TI  - The 1906 San Francisco earthquake: a centennial contemplation.

PMID- 16892877
TI  - Military-civic action: lessons learned from a brigade-level aid project in the
      2003 war with Iraq.
AB  - The primary mission of the military physician assigned to a combat-arms unit is
      to sustain the unit's fighting strength through prevention, primary medical care,
      and trauma resuscitation. Technical and organizational details of civic action
      assistance are not emphasized routinely during training. Real-world deployment,
      however, presents challenges approachable only with flexibility and
      improvisation. Historically, combatant commanders have recognized the health of
      civilians in their operational area as a target through which local acceptance of
      United States (US) intervention may be achieved. The medium-unit (battalion and
      brigade) physician may be charged with providing care to the host-nation
      populace. Because the mission's emphasis is one of public relations and not
      sustainable development, lasting medical benefits are not attained. This article
      addresses the challenge of on-the-spot military civic assistance. The experience
      of the 173d Airborne Brigade (Bde) Medical Section is used to color concepts with
      real events. The unit attempted to reach beyond the immediate directive in order
      to create a program of lasting results.

PMID- 16892878
TI  - International medical response to a natural disaster: lessons learned from the
      Bam earthquake experience.
AB  - An earthquake measuring 6.5 on the Richter scale devastated Bam, Iran on the
      morning of 26 December 2003. Due to the great health demands and collapse of
      health facilities, international aid could have been a great resource in the
      area. Despite sufficient amounts and types of resources provided by international
      teams, the efficacy of international assistance was not supported in Bam, as has
      been experienced in similar events in other countries. Based on the observations
      in the region and collecting and analyzing documents about the disaster, this
      manuscript provides an overview of the medical needs during the disaster and
      describes the international medical response. The lessons learned include: (1)
      necessity of developing a national search and rescue strategy; (2) designing an
      alarm system; (3) establishing an international incident command system; (4)
      increasing the efficacy of the arrival and implementation of a foreign field
      hospital; and (5) developing a flowchart for deploying international assistance.

PMID- 16892879
TI  - In the path of disasters: psychosocial issues for preparedness, response, and
      recovery.
AB  - The psychosocial impacts of disasters are profound. In recent years, there have
      been too many reminders of these impacts and the dire needs of the people
      involved. The purpose of this article is to present the following themes from the
      psychosocial literature on disasters and emergency management: (1) differential
      impacts of disasters according to gender and age; (2) prevention efforts to
      reduce racial discrimination, rape, and other forms of abuse; (3) readiness for
      cultural change toward prevention and preparedness; and (4) the need to involve
      aid beneficiaries as active partners in relief strategies, particularly during
      reconstruction of communities and critical systems. Psychosocial needs change
      throughout the disaster cycle, particularly as social support deteriorates over
      time. It is important to anticipate what psychosocial needs of the public,
      emergency responders, support staff, and volunteers might emerge, before
      advancing to the next stage of the disaster. Particular consideration needs to be
      directed toward differential impacts of disasters based on gender, age, and other
      vulnerabilities.

PMID- 16892880
TI  - Disaster health education and training: a pilot questionnaire to understand
      current status.
AB  - In October 2004, a World Association for Disaster and Emergency Medicine (WADEM)
      Seminar was convened in Brusselsby the Education Committee to discuss Disaster
      Education and Training. During this seminar, it became apparent that there was no
      single tool available to assess knowledge, skills, and resources within this
      field. Therefore, a tool was administered to 50 of the delegates to assess if the
      tool would facilitate information-sharing and curriculum development in disaster
      health education. The WADEM Education Committee devised a reference scheme for
      disaster health training and education based on seven educational levels within a
      framework based on the Bradt model. A questionnaire was developed to answer
      questions regarding current practices in disaster health education and training,
      and the perceived barriers to creating an international system of standards,
      guidelines, and accreditation. The questionnaire was sent to all of the delegates
      and the responses were analyzed. The questionnaire was useful for information
      sharing and curriculum development. Based on the respondents' experience,
      strategies were put forward for adopting better coordinated framework for
      disaster health education and training. This questionnaire should be updated and
      repeated annually within the WADEM. Wider use of the tool is recommended to help
      evaluate current educational resources in disaster health and in the wider
      educational field. It could facilitate the development and audit of current and
      future courses. An international system for education and training should lead to
      more efficient and coordinated health responses to disasters.

PMID- 16892881
TI  - Frequency of post-traumatic stress disorder among relief force workers after the
      tsunami in Asia: do rescuers become victims?
AB  - OBJECTIVE: The objective of this study was to evaluate the frequency of
      posttraumatic stress disorder (PTSD) among the participants of the Turkish Red
      Crescent Disaster Relief Team after the Tsunami in Asia. METHODS: The Clinician
      Administered PTSD Scale-1 (CAPS-1) was administered to 33 of 36 team members one
      month after their Disaster Relief Team duty. Along with the CAPS-1 interview,
      demographic features, profession, previous professional experience, previous
      experience with traumatic events and disasters also were recorded. To be
      classified as present, a symptom must have a frequency score of "1" and an
      intensity score of "2" at the CAPS-1 interview. For a diagnosis of PTSD, at least
      one re-experiencing, three avoidance and numbing, and two increased arousal
      symptoms should be present. RESULTS: The PTSD was diagnosed in eight of the 33
      (24.2%) participants. No significant difference was detected in the distribution
      of PTSD diagnosis according to gender, age, profession, professional experience,
      previous disaster experience, and/or previous experience of traumatic events.
      However, the severity of PTSD symptoms as measured by the CAPS-1 score was
      significantly higher in women, nurses, and participants with <3 previous disaster
      duty experiences. CONCLUSION: Post-traumatic stress disorder is prevalent within
      disaster teams and healthcare workers, and measures should be taken to prevent
      PTSD within this group.

PMID- 16892882
TI  - Role of exercises and drills in the evaluation of public health in emergency
      response.
AB  - INTRODUCTION: Public health agencies have been participating in emergency
      preparedness exercises for many years. A poorly designed or executed exercise, or
      an unevaluated or inadequately evaluated plan, may do more harm than good if it
      leads to a false sense of security, and results in poor performance during an
      actual emergency. At the time this project began, there were no specific
      standards for the public health aspects of exercises and drills, and no defined
      criteria for the evaluation of agency performance in public health. OBJECTIVE:
      The objective of this study was to develop defined criteria for the evaluation of
      agency performance. METHOD: A Delphi panel of 26 experts in the field
      participated in developing criteria to assist in the evaluation of emergency
      exercise performance, and facilitate measuring improvement over time. Candidate
      criteria were based on the usual parts of an emergency plan and three other
      frameworks used elsewhere in public health or emergency response. RESULTS: The
      response rate from the expert panel for Delphi Round I was 74%, and for Delphi
      Round II was 55%. This final menu included 46 public health-agency level criteria
      grouped into nine categories for use in evaluating an emergency drill or exercise
      at the local public health level. CONCLUSION: Use of the public health-specific
      criteria developed through this process will allow for specific assessment and
      planning for measurable improvement in a health agency over time.

PMID- 16892883
TI  - Knowledge of severe acute respiratory syndrome among community physicians,
      nurses, and emergency medical responders.
AB  - INTRODUCTION: The preparedness levels of front-line clinicians including
      physicians, nurses, emergency medical responders (EMRs), and other medical staff
      working in clinics, offices and ambulatory care centers must be assessed, so
      these personnel are able to deal with communicable and potentially lethal
      diseases, such as severe acute respiratory syndrome (SARS). In order to determine
      the knowledge of these clinicians, a survey of their understanding of SARS and
      their use of educational resources was administered. METHODS: A questionnaire was
      distributed to physicians, nurses, and EMRs attending conferences on SARS in the
      summer of 2003. Questions related to information sources, knowledge of SARS, and
      plans implemented in their workplace to deal with it. Statistical analysis was
      performed using the Statistical Package for the Social Sciences (10.1 Program,
      SPSS Inc., Chicago, Illinois). RESULTS: A total of 201 community healthcare
      providers (HCPs) participated in the study. A total of 51% of the participants
      correctly identified the incubation period of SARS; 48% correctly identified the
      symptoms of SARS; and 60% knew the recommended infection control precautions to
      take for families. There was little difference in knowledge among the physicians,
      nurses, and EMRs evaluated. Media outlets such as newspapers, journals,
      television, and radio were reported as the main sources of information on SARS.
      However, there appears to be a growing use of the Internet, which correlated best
      with the correct answers on symptoms of SARS. Fewer than one-third of respondents
      were aware of a protocol for SARS in their workplace. A total of 60% reported
      that N-95 masks were available in their workplace. CONCLUSION: These findings
      suggest the need for more effective means of education and training for front
      line clinicians, as well as the institution of policies and procedures in medical
      offices, clinics, and emergency services in the community.

PMID- 16892884
TI  - Changes in level of consciousness and association with hyperglycemia as tool for
      predicting and preventing re-bleeding after spontaneous subarachnoid hemorrhage.
AB  - INTRODUCTION: It is crucial to predict and prevent re-bleeding from ruptured
      intracranial aneurysms in patients with subarachnoid hemorrhage (SAH). During the
      prehospital period and on arrival to the hospital, blood glucose and serum
      potassium levels, as well as changes in levels of consciousness were assessed in
      patients in the acute stage of spontaneous subarachnoid hemorrhage. These
      assessments were analyzed as possible risk factors for re-bleeding and as
      potential contributors to the prevention of re-bleeding, both in prehospital care
      and after hospital admission. METHODS: Upon the arrival of 202 patients with
      spontaneous subarachnoid hemorrhage, the following indications were examined
      retrospectively: (1) presence/absence of re-bleeding; (2) time interval between
      the onset of SAH and re-bleeding; (3) level of consciousness using the Glasgow
      Coma Scale (GCS) score before and on arrival; (4) amount and distribution of
      subarachnoid blood using Fisher's Computerized Tomography Classification; (5)
      blood pressure; (6) blood glucose concentration; and (7) serum potassium
      concentration. The patients were hospitalized in the Yokohama City University
      Critical Care and Emergency Center (Yokohama, Japan) between January 1991 and
      December 2000. The re-bleeding rate was analyzed using the chi-square (chi2 test,
      and the averages and standard deviations of hematological data were compared
      using the Mann-Whitney U-test. The level of statistical significance was set at p
      < 0.05. RESULTS: The overall re-bleeding rate was 20.8%. Among 119 patients with
      a GCS score of 3-7 before arrival, 42 (35.3%) had re-bleeding, but none of the 83
      patients with a GCS score of 8-15 before arrival had re-bleeding. Of 105 patients
      with a GCS score of 13-15 on arrival, 14 (51.8%) of 27 patients whose
      consciousness level was a GCS score of 3-7 before arrival experienced re
      bleeding. The re-bleeding rate of this group was high. Moreover, this rebleeding
      group had a significantly higher blood glucose concentration than did the
      patients whose GCS score was 13-15 both before and on arrival. Between the
      patients with or without re-bleeding, there was no significant difference in the
      blood pressure on arrival or in distribution according to Fisher's Computerized
      Tomography Classification CONCLUSION: Since the re-bleeding rate is high in
      patients who have hyperglycemia and a history of a level of consciousness as low
      as a GCS score of 3-7, a detailed assessment of level of consciousness and blood
      glucose tests performed on arrival provide important information that will
      contribute to predicting and preventing re-bleeding. This may be extended to the
      prehospital phase, because blood glucose tests are simple and safe when performed
      by paramedics.

PMID- 16892885
TI  - Disaster management following the Chi-Chi earthquake in Taiwan.
AB  - The earthquake that occurred in Taiwan on 21 September 1999 killed >2,000 people
      and severely injured many survivors. Despite the large scale and sizeable impact
      of the event, a complete overview of its consequences and the causes of the
      inadequate rescue and treatment efforts is limited in the literature. This review
      examines the way different groups coped with the tragedy and points out the major
      mistakes made during the process. The effectiveness of Taiwan's emergency
      preparedness and disaster response system after the earthquake was analyzed.
      Problems encountered included: (1) an ineffective command center; (2) poor
      communication; (3) lack of cooperation between the civil government and the
      military; (4) delayed prehospital care; (5) overloading of hospitals beyond
      capacity; (6) inadequate staffing; and (7) mismanaged public health measures. The
      Taiwan Chi-Chi Earthquake experience demonstrates that precise disaster planning,
      the establishment of one designated central command, improved cooperation between
      central and local authorities, modern rescue equipment used by trained disaster
      specialists, rapid prehospital care, and medical personnel availability, as well
      earthquake-resistant buildings and infrastructure, are all necessary in order to
      improve disaster responses.

PMID- 16892886
TI  - Prehospital care of tsunami victims in Thailand: description and analysis.
AB  - INTRODUCTION: On 26 December 2004 at 09:00 h, an earthquake of 9.0 magnitude
      (Richter scale) struck the area off of the western coast of northern Sumatra,
      Indonesia, triggering a Tsunami. As of 25 January 2005, 5,388 fatalities were
      confirmed, 3,120 people were reported missing, and 8,457 people were wounded in
      Thailand alone. Little information is available in the medical literature
      regarding the response and restructuring of the prehospital healthcare system in
      dealing with major natural disasters. OBJECTIVE: The objective of the study was
      to analyze the prehospital medical response to the Tsunami in Thailand, and to
      identify possible ways of improving future preparedness and response. METHODS:
      The Israeli Defense Forces (IDF) Home Front Command Medical Department sent a
      research delegation to study the response of the Thai medical system to the 2004
      earthquake and Tsunami disaster. The delegation met with Thai healthcare and
      military personnel, who provided medical care for and evacuated the Tsunami
      victims. The research instruments included questionnaires (open and closed
      questions), interviews, and a review of debriefing session reports held in the
      days following the Tsunami. RESULTS: Beginning the day after the event, primary
      health care in the affected provinces was expanded and extended. This included:
      (1) strengthening existing primary care facilities with personnel and equipment;
      (2) enhancing communication and transportation capabilities; (3) erecting
      healthcare facilities in newly constructed evacuation centers; (4) deploying
      mobile, medical teams to make house calls to flood refugees in affected areas;
      and (5) deploying ambulance crews to the affected areas to search for survivors
      and provide primary care triage and transportation. CONCLUSION: The restructuring
      of the prehospital healthcare system was crucial for optimal management of the
      healthcare needs of Tsunami victims and for the reduction of the patient loads on
      secondary medical facilities. The disaster plan of a national healthcare system
      should include special consideration for the restructuring and reinforcement
      prehospital system.

PMID- 16892887
TI  - Medical response of a physician and two nurses to the mass-casualty event
      resulting in the Phi Phi Islands from the tsunami.
AB  - The Phi Phi Islands are isolated islands located about one hour by ship from the
      mainland in Krabi province of Thailand. There is a small medical facility where
      the director is the one physician that provides care to residents and tourists.
      This small medical facility faced an enormous mass casualty incident due to the
      2004 Tsunami. The hospital was damaged by the Tsunami wave and was not
      functional, one crew member died and another was injured. Medical care and
      evacuation posed a unique problem in the Phi Phi Islands due to remoteness,
      limited medical resources, lack of effective communication with the main land and
      the large number of victims. An alternative medical facility was located in a
      nearby hotel. The crew included the medical director, two nurses, two additional
      staff members, 10 local volunteers, and hotel staff members. The medical crew had
      to treat 600-700 casualties in 24 hours. Most of the victims were mildly injured,
      but approximately 100 (15%) of the victims could not walk due to their injuries.
      The medical director, made a conscious decision to initially treat only
      circulation ("C") problems, by controlling external hemorrhages. This decision
      was driven by the lack of equipment and personnel to deal with airway ("A") and
      breathing ("B") problems. In the post-disaster debriefing, the Phi Phi Island
      hospital physician noted five major lessons concerning disaster management in
      such extreme situation in a small facility located in a remote area: (1)
      effective resistant communication facilities must be ensured; (2) clear, simple
      "evacuation plans" should be made in advance; (3) plans should be made to ensure
      automatic reinforcement of remote areas with evacuation vehicles, medical
      equipment and medical personnel; (4) efficient cooperation with medical
      volunteers must be planned and drilled; and (5) every team member of such a
      hospital must participate in an educational program and periodic drills should be
      done to improve the disaster and emergency medicine capabilities. This case
      report is an example for caregivers all over the world, of an amazing lesson of
      leadership and courage.

PMID- 16892888
TI  - Medical support for emergency relief workers after typhoon Sudal in Yap,
      Micronesia.
AB  - INTRODUCTION: On 09 April 2004, Typhoon Sudal struck the Island of Yap in the
      Federated States of Micronesia (FSM). Over 90% of homes, public utilities, and
      public property were damaged or destroyed. Nearly 10% of the population was
      displaced to shelters, and the majority of the population was without drinking
      water or power. United States disaster workers were deployed to Yap for three
      months to assist in the recovery and relief efforts. OBJECTIVE: The objective of
      this study was to evaluate the acute healthcare needs of the US disaster relief
      population serving in a remote setting with limited medical resources. METHODS: A
      retrospective chart review of all disaster relief workers presenting to an
      emergency clinic in Yap during the disaster relief effort from April 2004-July
      2004 was performed. Investigators extracted demographic data, chief complaints,
      medical histories, medical management, disposition, and outcome data from the
      clinic charts. RESULTS: Together, the 60 disaster workers present on Yap during
      the relief effort made 163 patient contacts in the disaster emergency clinic. A
      total of 92% of patient contacts were for minor medical complaints or minor
      trauma, 13% were for upper-respiratory infections, 9% were for gastrointestinal
      illness, and 9% were for dermatological problems. Eight percent of visits were
      for serious medical problems or trauma. Life-threatening illnesses or injuries
      did not occur. CONCLUSIONS: Disaster relief workers on Yap frequently utilized
      the disaster relief clinic. In general, disaster workers remained healthy during
      the relief effort in Yap, and most injuries and illnesses were minor. On-site
      medical providers resulted in rapid care and stabilization, and after treatment,
      disaster workers were able to return to duty.

PMID- 16892889
TI  - Precision of in-hospital triage in mass-casualty incidents after terror attacks.

PMID- 16892890
TI  - [Recommendation for using granulocyte and granulocyte-macrophage growth factor
      during anti-cancer therapy in children].
AB  - Neutropenia is the most often side effect during antineoplastic treatment. In
      this article current recommendations for clinical applications of granulocyte and
      granulocyto-macrophage hematopoietic factors and possibility of protection of
      neutropenia, and its serious complications in pediatric oncology are presented.

PMID- 16892891
TI  - [Treatment results in children with the standard risk acute lymphoblastic
      leukemia treated with high dose of methotrexate (5.0 g/m2). 11 years of the
      Polish Pediatric Leukemia/Lymphoma Study Group experience].
AB  - Since 01.07.1993 to 30.09.2004, 675 children with ALL-SR were diagnosed and
      treated according to the modified ALL-BFM 90 protocol. Subject to statistical
      analysis (Kaplan-Meier method) were thus 197 children with ALL-SR treated with HD
      MTX in a dose 5.0g/ m2. Among them, 21 patients failed to respond to therapy: 2
      (1.0%) early deaths, 2 (1.0%) deaths during I complete remission, 16 (8.2%)
      relapses, 1 (0.5%) second neoplasm. Relapses occured: 12 (6.2%) in bone marrow, 2
      (1.0%) in central nervous system, 1 (0.5%) in testicle and in 1 (0.5%) child
      combined relapse was observed. Probability rates for 11-year event free survival
      (EFS) was 0.80 (0.03). Application of high dose of methotrexate is safety and
      effective in prevention of relapses, especially meningeal and testicular
      involvement.

PMID- 16892893
TI  - [Assessment of elimination and tolerance of high dose of methotrexate (3 g/m2) in
      children with standard-risk acute lymphoblastic leukemia].
AB  - We assessed correlation between the elimination of methotrexate administered in
      dose 3 g/m2 during consolidation phase and the early complications in 129
      children treated for acute lymphoblastic leukemia. Among 500 chemotherapy cycles
      included in the analysis the elimination of methotrexate was delayed in 66
      (13.2%) cycles in 43 (33.3%) of patients. Influence of methotrexate on selected
      liver and renal function tests was analyzed. We made an attempt of early
      identification of patients with high risk for delayed methotrexate elimination
      and subsequent toxicities.

PMID- 16892892
TI  - [Acute lymphoblastic leukemia in children with initial leucocytosis above
      50,000/mm3: summary of treatment results of Polish Pediatric Leukemia/Lymphoma
      Study Group].
AB  - Initial leucocytosis, presence of t(9;22) and t(4;11) translocations and poor
      response to therapy with steroids or induction chemotherapy are still included to
      poor risk factors group. From 1981 to 1986, children with acute lymphoblastic
      leukemia (ALL) and initial WBC above 50,000/mm3, achieved significantly worse
      treatment results than children with lower WBC: over 6-year disease-free survival
      were respectively 33% and 60%. In attempt to improve treatment results in
      children with hyperleucocytosis, modified American protocols called: New York
      (1987), New York I (1997), and New York II (1999) were introduced consecutively
      in the centers of Polish Pediatric Leukemia/ Lymphoma Study Group. Actually
      treatment results obtained with those protocols in three groups of patients:
      group I: 214 children (1987-1996), group II: 58 children (1997-1999), and group
      III: 77 children (1999-2001) are presented. The observation was completed in
      March 31, 2004. In evaluated groups the first complete remissions (CR) were
      achieved in 91%, 95%, and 96% of patients, respectively. Relapses occurred in 72
      patients of group I (37%), in 12 patients of group II (21%), and in 13 patients
      of group III (18%). The 5-year overall survivals were: 62%, 79%, and 78% (p=0.05)
      respectively; 5 year event-free survivals (EFS) were: 52%, 74%, and 69% (p=0.01)
      respectively. A significant improvement in treatment results in second compared
      with first group was achieved. Treatment results obtained with New York II are
      comparable with results obtained with New York I. The analysis of treatment
      results achieved shows the improvement of the prognosis in children with ALL and
      initial WBC above 50 000/mm3 in comparison with patients treated before 1987.
      There is strong necessity of unification of risk group qualification criteria in
      childhood ALL in term of comparable estimation treatment results achieved in
      different centers all over the world.

PMID- 16892895
TI  - [The health state evaluation in persons after therapy of Hodgkin's disease in
      childhood: report of the Polish Pediatric Leukemia/Lymphoma Study Group].
AB  - The introduction of modern methods of combined therapy: chemotherapy and
      radiotherapy, allows the cure more than 90% of children and adolescents with
      Hodgkin's disease. However, the intensive treatment may cause early and late
      complications. The late complications may include: damage of soft tissues and
      respiratory, cardiovascular, skeletal, and endocrine systems, and second cancers.
      Late complications may impair the patients' quality of life after cessation of
      therapy. This study presents evaluation of health status of persons who underwent
      therapy for pediatric Hodgkin's disease in centers of Polish Pediatric
      Leukemia/Lymphoma Study Group. The special questionnaire was established to
      collect data concerning hematopoietic system function, damage of soft tissues and
      skeletal system, thyroid and reproductive organs function, respiratory,
      cardiovascular, and nervous system function, liver and kidney function, status of
      dentition, occurrence of infections, immunologic system function, and
      psychological and social problems. The project included patients treated in 9
      pediatric oncology centers. During the study the questionnaires of 288 patients
      [151 boys (52.4%) and 137 girls (47.6%)] in whom treatment of Hodgkins's disease
      started in 1994-1996 (44 questionnaires), and in 1997-2001 (244 questionnaires).
      In 42 patients no diagnostic procedures were performed. In this group 20 patients
      are currently under care of adult oncology clinics, 21 failed to come for a
      visit, and one patient is treated because of HD progression. The questionnaires
      of 246 patients treated in 1994-1996 (25 questionnaires) and 1997-2001 (221
      questionnaires), were analyzed and the data on the late complications of these
      patients were obtained. General health status of examined patients was found
      satisfactory. However, 2.3% of patients had radiological evidence of pulmonary
      fibrosis, and 4.9% had various ECG abnormalities. Endocrine therapy is needed in
      4.5% of patients because of thyroid function abnormalities. Second cancers were
      diagnosed in 1.7% of patients. The health status of children and adolescents
      cured from Hodgkin's disease and other childhood cancers should be regularly
      evaluated. Results of these evaluations will be the basis for introducing new
      treatment protocols aimed of decreasing the incidence of late complications while
      maintaining or improving cure rates.

PMID- 16892894
TI  - [Does the residual mediastinal mass have prognostic significance in children with
      Hodgkin's disease (HD)?].
AB  - Prognostic significance of residual mediastinal tumor mass in children treated
      for HD as well as the choice of the optimal management of these cases still
      remains unknown. In years 1994-2001 in 10 PPLLSG participating centers 480
      children (age 2-19.7 years) were treated for HD (stages I-IV). In 338 cases
      initial mediastinal/lung hilus involvement was present. All patients with initial
      mediastinal/lung hilus involvement were treated with multidrug chemotherapy
      combined with involved field radiotherapy. In five cases remission was not
      achieved. Complete remission (CR) was achieved in 226 patients and uncertain
      complete remission (UCR) in 107 patients, in whom after completion of planned
      treatment residual changes in mediastinum/lung hilus were identified in
      radiological examinations. Twenty four children with persistent mediastinal tumor
      underwent thoracoscopy or thoracotomy. In only one case histopathological
      examination revealed the presence of neoplastic cells in mediastinal mass tissue,
      in 2 another cases cystic changes in mediastinum were present, in one case thymic
      tissue was identified, necrotic tissue was present in 20 cases. Among 107
      children with residual mediastinal tumor and 226 patients with CR achieved,
      relapses occurred in 6 and 18 patients respectively. Over 5-year relapse-free
      survival was 92.4% and 91.3% respectively. Patients with the presence of
      mediastinal/lung hilus tumor after the completion of the treatment do not have an
      increased risk of relapse, but before the completion of therapy they require
      careful, clear-sighted and repeated examinations including computed tomography
      (CT), magnetic resonance imaging (MRI) and especially positron emission
      tomography (PET) to evaluate the nature of persistent lesions. Only in clinically
      and radiologically doubtful cases tumor biopsy with subsequent histopatological
      examination should be performed.

PMID- 16892897
TI  - [Late complications of treatment for Hodgkin's disease in children and
      adolescents].
AB  - Based on our center's experience and data from literature we present the late
      complications of treatment in patients cured from Hodgkin's disease in childhood.
      The knowledge of the risk factors of side effects of treatment will allow to
      follow-up the patients effectively after cessation of therapy. The late
      complications may be life threatening (second cancers, severe organ damage) or be
      the cause of disability or impair the patient's quality of life. Reduction of
      rate of late complications in persons cured from Hodgkin's disease and other
      childhood cancers is a very important goal for pediatric oncologists.

PMID- 16892896
TI  - [What to improve in approach to diagnose and treat pediatric myelodysplastic
      syndromes and juvenile myelomonocytic leukemia in Poland?].
AB  - Group of heterogeneous clonal hematopoietic disorders usually associated with
      other genetic disorders called for myelodysplastic syndromes (MDS) are occurring
      less common in children. The WHO classification based on French-American-British
      (FAB) MDS morphology is widely accepted in adults but does substantially differe
      from the one applicable in children. The differencies have recently been
      published. In our national retrospective study we analyzed 99 children with MDS
      and JMML diagnosed between 1989 and 2003 in Poland. Chemotherapy is generally,
      not useful in childhood MDS. With a few exceptions hematopoieitic stem cell
      transplantation (HSCT) is the only curative treatment for children with MDS. In
      this nationalexperience use of a relative or an unrelated donor results are
      almost comparable to the internationally published ones. Successful management of
      the disease needs to be run on a basis of cooperative efforts between clinicians
      and scientists involved in pediatric MDS. This includes need for centralized
      update and morphologic re-evaluation of all patients in the country as well as
      appointments on a regular basis for all individuals involved in treatment of MDS
      for quality control.

PMID- 16892898
TI  - [Program of care for children and adolescents after completion of therapy for
      cancer].
AB  - Based on our center's experience and data from literature we present a system of
      care for patients cured from cancer in childhood. The scope of proposed care will
      be to increase the rate of detection of late complications, improve efficacy of
      medical care, improve quality of research, and introduce changes in treatment
      regimens in order to decrease the incidence of late complications of treatment
      while maintaining or even improving cure rates and reduce cost of care.

PMID- 16892899
TI  - [Minimal residual disease in childhood acute leukemias].
AB  - Monitoring of residual leukemic cells, so called minimal residual disease (MRD)
      in acute leukemias is of great importance in clinical practice. Especially
      evaluation of early response to treatment has a important prognostic value, and
      modifies the therapy schedule in a nowadays used treatment protocols. Methods
      used for monitoring of MRD consist of molecular techniques, which detect
      chromosomal aberrations or immunoglobulins and lymphocyte T receptor genes
      rearrangements, as well as method of flow cytometry, which detect immunophenotype
      typical for the leucemic clone. The paper shows advantages and disadvantages each
      of those methods. The best approach to monitoring MRD in ALL during and after the
      treatment seems to be combination of molecular and immunological techniques.

PMID- 16892900
TI  - [Significance of L-asparaginase activity and biochemical parameters evaluation in
      children with acute lymphoblastic leukemia].
AB  - L-asparaginase is one of the most important agent used in multidrug chemotherapy
      regimens in the treatment of malignancies which derive from lymphoid system
      (acute lymhoblastic leukemias and non-hodgkin lymphoma). L-asparaginase leads to
      enzymatic cleavage of L-asparagine (amino acid essential for lymphoblasts'
      growth) to ammonia and L-aspartic acid, what results in depletion of L-asparagine
      in a serum and cerebrospinal fluid, and finally leads to destruction of
      lymphoblasts, which lack ability of endogenic L-asparagine production. In the
      course of L-asparaginase therapy severe side effects could be observed such as:
      coagulation disturbances, acute pancreatitis, anaphilactic shock and other types
      of allergic reaction, as well as liver and CNS failure. Monitoring of L
      asparaginase activity in serum is recomended in order to optimalize therapy with
      L-asparaginase and reducing risk of severe side effects. Continuous assessment of
      L-asparaginase activity during therapy gives also opportunity to detect
      asymptomatic inactivation of L-ASPA - so called "silent inactivation", which is
      cused by production of antibodies against xenogenic protein, especcialy in IgG
      class. This process leads to shortening of half-life of L-ASPA. The paper shows
      presently available monitoring methods during therapy with L-ASPA, with all their
      pros and cons.

PMID- 16892901
TI  - [Hemophagocytic syndrome: diagnostic problems].
AB  - Hemophagocytic syndrome (HS) is a rare but life-threatening disease caused by
      inappropriate activation of T-lymphocytes and histiocytes, hipercytokinemia and
      hemophagocytosis. The most common symptoms are fever, hepatosplenomegaly,
      unspecific neurological abnormalities, pancytopenia, coagulopathy,
      hiperferritinemia and lipid abnormalities. HS is classified into two forms:
      primary, inherited (Familial Hamophagocytic Lymphohistiocytosis--FHL) and
      secondary (associated with infection, malignancy, autoimmune disease). In spite
      of the fact that diagnostic guidelines are available it often remains
      unrecognised. Prognosis of HS depends on the form of disease and in case of
      secondary HS on the underlying disease. Development of the treatment protocols
      (HLH-94, HLH-2004) which combine immunochemiotherapy with hematopoietic stem cell
      transplantation has strongly improved prognosis in HS especially in the primary
      form. Three-year overall survival for children with HS is now over 50%. Early
      diagnosis and appropriate therapy is crucial for effectiveness of the treatment.
      Popularisation of the knowledge about the syndrome, diagnostic guidelines and
      treatment protocols can contribute to more frequent appropriate recognition of HS
      and to improvement of the treatment results.

PMID- 16892902
TI  - Guest editorial--preventive vaccines.

PMID- 16892903
TI  - Vaccine clinical trials--a statistical primer.
AB  - We discuss some of the key statistical issues that arise in all stages of vaccine
      development and, where necessary, contrast drug and vaccine clinical trials.

PMID- 16892904
TI  - Overview of vaccine field studies: types of effects and designs.
AB  - Vaccination produces many different types of effects in individuals and in
      populations. The scientific and public health questions of interest determine the
      choice of measures of effect and study designs. Here we review some of the
      various measures and study designs for evaluating different effects of
      vaccination.

PMID- 16892906
TI  - Statistical analysis of influenza vaccine lot consistency studies.
AB  - This paper presents an integrated statistical approach to the analysis of
      influenza vaccine lot consistency studies in which three lots are compared. The
      approach ensures that the overall Type I error rate (i.e., the probability of
      wrongly concluding that the lots are similar) is controlled. It is argued that
      the optimum efficacy measure is the geometric mean titer. The approach is
      demonstrated using data from a randomized, double-blind lot consistency study in
      which three consecutive production lots of Solvay Pharmaceuticals' new, virosomal
      subunit influenza vaccine Invivac were compared.

PMID- 16892905
TI  - Statistical considerations for noninferiority/equivalence trials in vaccine
      development.
AB  - Noninferioritylequivalence designs are often used in vaccine clinical trials. The
      goal of these designs is to demonstrate that a new vaccine, or new formulation or
      regimen of an existing vaccine, is similar in terms of effectiveness to the
      existing vaccine, while offering such advantages as easier manufacturing, easier
      administration, lower cost, or improved safety profile. These
      noninferioritylequivalence designs are particularly useful in four common types
      of immunogenicity trials: vaccine bridging trials, combination vaccine trials,
      vaccine concomitant use trials, and vaccine consistency lot trials. In this
      paper, we give an overview of the key statistical issues and recent developments
      for noninferioritylequivalence vaccine trials. Specifically, we cover the
      following topics: (i) selection of study endpoints; (ii) formulation of the null
      and alternative hypotheses; (iii) determination of the noninferioritylequivalence
      margin; (iv) selection of efficient statistical methods for the statistical
      analysis of noninferioritylequivalence vaccine trials, with particular emphasis
      on adjustment for stratification factors and missing pre-or post-vaccination
      data; and (v) the calculation of sample size and power.

PMID- 16892907
TI  - Evaluation of the indirect effects of a pneumococcal vaccine in a community
      randomized study.
AB  - When a sufficiently high proportion of a population is immunized with a vaccine,
      reduction in secondary transmission of disease can confer significant protection
      to unimmunized population members. We propose a straightforward method to
      estimate the degree of this indirect effect of vaccination in the context of a
      community-randomized vaccine trial. A conditional logistic regression model that
      accounts for within-randomization unit correlation over time is described, which
      models risk of disease as a function of community-level covariates. The approach
      is applied to an example data set from a pneumococcal conjugate vaccine study,
      with study arm and immunization levels forming the covariates of interest for the
      investigation of indirect effects.

PMID- 16892908
TI  - On the use of zero-inflated and hurdle models for modeling vaccine adverse event
      count data.
AB  - We compared several modeling strategies for vaccine adverse event count data in
      which the data are characterized by excess zeroes and heteroskedasticity. Count
      data are routinely modeled using Poisson and Negative Binomial (NB) regression
      but zero-inflated and hurdle models may be advantageous in this setting. Here we
      compared the fit of the Poisson, Negative Binomial (NB), zero-inflated Poisson
      (ZIP), zero-inflated Negative Binomial (ZINB), Poisson Hurdle (PH), and Negative
      Binomial Hurdle (NBH) models. In general, for public health studies, we may
      conceptualize zero-inflated models as allowing zeroes to arise from at-risk and
      not-at-risk populations. In contrast, hurdle models may be conceptualized as
      having zeroes only from an at-risk population. Our results illustrate, for our
      data, that the ZINB and NBH models are preferred but these models are
      indistinguishable with respect to fit. Choosing between the zero-inflated and
      hurdle modeling framework, assuming Poisson and NB models are inadequate because
      of excess zeroes, should generally be based on the study design and purpose. If
      the study's purpose is inference then modeling framework should be considered.
      For example, if the study design leads to count endpoints with both structural
      and sample zeroes then generally the zero-inflated modeling framework is more
      appropriate, while in contrast, if the endpoint of interest, by design, only
      exhibits sample zeroes (e.g., at-risk participants) then the hurdle model
      framework is generally preferred. Conversely, if the study's primary purpose it
      is to develop a prediction model then both the zero-inflated and hurdle modeling
      frameworks should be adequate.

PMID- 16892909
TI  - Patterns of immune response to a vaccine or virus as measured by intracellular
      cytokine staining in flow cytometry: hypothesis generation and comparison of
      groups.
AB  - Candidate HIV vaccines must show an immune response in order to be considered for
      further testing and development. What constitutes a "response," however, is still
      not clear. While the hunt for a protective vaccine continues, hypotheses are
      being formed by studying the immune responses across cohorts of people with
      differing responses to the infection, as well as the immune responses formed by
      healthy people to other viruses, ones that are generally common and well
      controlled. Here we examine the functional profile of the immune responses of a
      group of HIV+ long-term non-progressors as measured by intracellular cytokine
      staining using polychromatic flow cytometry, and compare these responses to those
      of a larger group of other HIV+ people. We describe some of the types of patterns
      in immune response that are of interest to vaccine researchers, and compare
      several statistical tests appropriate for this type of data.

PMID- 16892910
TI  - Estimating vaccine efficacy from outbreak size household data in the presence of
      heterogeneous transmission probabilities.
AB  - We develop a Bayesian approach for estimating vaccine efficacy for susceptibility
      (VEs) and infectiousness (VEI) using outbreak size household data. Our method
      allows for heterogeneity in transmission probabilities due to factors that are
      related to individuals' characteristics, such as age, in addition to vaccination
      status. It also allows for between-household heterogeneity in transmission
      probabilities due to random effects associated with households, such as genetic
      or environmental effects. Using age as a potential covariate causing
      heterogeneity in individuals' transmission probabilities in households consisting
      of adults and children, we present the results of a simulation study designed to
      evaluate the performance of the proposed estimators of VEs and VE(I). We found
      that estimates of VE(I) have larger bias and variance compared to those of VEs.
      We also use the approach to compare two vaccination designs: one vaccinating both
      adults and children, the other only children. Simulations reveal that the design
      that vaccinates both adults and children provides better estimates of VEs. There
      is no obvious difference between the two designs in the performance of the
      estimates of VE(I). In regard to random effects between households and the
      scenarios considered, models that do not account for between-households
      heterogeneity produce fairly robust estimates even when household-level random
      effects are present.

PMID- 16892911
TI  - Joint inferences on vaccine efficacy against infection and disease with
      application to the first HIV vaccine efficacy trial.
AB  - In many clinical trials, subjects are followed for two stages of outcomes, and it
      is of interest to compare the incidence of each outcome between two randomized
      groups. The outcome of the first stage may influence the outcome of the second
      stage. Moreover, the relative risks of the two outcomes may be linked, with the
      time-dependent profile of relative risk for the second outcome functionally
      dependent on that of the first. For example, during exposure to HIV, virologic
      and host factors simultaneously impact the probability of infection and the
      subsequent viral trajectories, and the efficacy of a tested vaccine to prevent
      infection and to prevent viral failure may work in concert. We address this
      problem by modeling the relationship between the stage two hazard function and
      covariates via Cox's proportional hazards model (Cox, 1972), with the stage one
      log-hazard ratio theta(*) at the first event time Tl, included as a covariate.
      With theta(*) estimated using three methods, 1) nonparametric kernel smoothing;
      2) locally parametric penalized splines; and 3) fully parametric cubic linear
      splines, we subsequently develop inference procedures for the regression
      parameter in the stage two Cox model based on each of the estimator of theta(*).
      The inferential procedures are studied in simulations and are illustrated with
      application to data from the world's first preventive HIV vaccine efficacy trial.

PMID- 16892912
TI  - Multistage designs for vaccine safety studies.
AB  - In a placebo-controlled vaccine safety trial, the primary interest is to
      demonstrate that the vaccine is sufficiently safe, rejecting the null hypothesis
      that the relative risk of an adverse event attributable to the vaccine is above a
      prespecified value, greater than one. We develop sequential as well as multistage
      designs for such trials where the interim analyses are conducted not after a
      given number of subjects but rather after a given number of events observed. We
      show that these designs achieve significant improvement over single-stage
      conditional test in terms of both the required number of events to be observed
      and the required number of subjects to be enrolled.

PMID- 16892913
TI  - Design of vaccine equivalence/non-inferiority trials with correlated multiple
      binomial endpoints.
AB  - Immunogenicity trials that study the immune responses to vaccination are often
      used in the vaccine development process as alternatives to clinical efficacy
      trials. The comparisons of immune responses among various treatment groups are
      conducted in a non-inferiority or equivalence framework. When there exists a
      level of immune response that correlates with protection against disease, it is
      of interest to compare the proportion of responders as defined as response above
      a specific level or as a predefined increase in immune levels for post
      vaccination levels above pre-vaccination levels. Since vaccines often contain
      several antigens, the correlations between the immune responses need to be taken
      into account in the analysis. In this paper, we describe appropriate testing
      methods for demonstrating the non-inferioritylequivalence of two treatments on
      each of the binomial endpoints. We conduct a comprehensive simulation study to
      shed light on how the Type I error and power are affected and to what extent when
      correlated multiple binomial endpoints are present in the vaccine trials. We also
      illustrate the computation of power for assessment of non-inferioritylequivalence
      in real studies.

PMID- 16892914
TI  - Casualty overcrowding and increased mortality: is it time to say no?

PMID- 16892915
TI  - Varicella outbreak in a residential home.
AB  - We report an outbreak of varicella in a residential home for 29 children(aged 4
      to 16 years) with severe physical and learning disability. We report our group's
      incidence, complication and hospitalisation rate of varicella despite anti-viral
      therapy. As we did not have a control group we use statistics pertaining to the
      general population for comparison. All 15 non-immune children contracted
      varicella within 30 days of the index case. The complication rate was 9 in 15,
      three time higher than in the general population. The hospitalisation rate was 5
      in 15. This is remarkably high. The incidence of hospitalisation in the general
      population is 1 to 5 per 1,000. In conclusion we suggest that the guidelines for
      varicella vaccination should include all non-immune children and adults with
      severe to profound physical and learning disability. We recommend that this
      disease should be notifiable in the severely physically disabled population. We
      recommend that within 3 days of exposure to varicella children with severe to
      profound physical and learning disability are vaccinated to prevent infection
      (post exposure prophylaxis). These findings are important in countries where
      varicella vaccination is not part of the routine vaccination program and is not
      part of the routine vaccination program and is only offered to select groups of
      children.

PMID- 16892916
TI  - The use of botulinum toxin in Frey's Syndrome.
AB  - Frey's Syndrome, or gustatory sweating, occurs in over 50% of patients following
      superficial parotidectomy. In the vast majority of cases, these symptoms are not
      severe enough to require surgical treatment and can be effectively treated with
      topical anticholinergics and antihyperhydrotics. Patients with recalcitrant
      Frey's Syndrome can be treated by a variety of surgical procedures. However, the
      potential risks and side effects of these surgical procedures often outweigh the
      benefits. Botulinum toxin A has recently emerged as a popular treatment option
      for a number of head and neck conditions. The anticholinergic effects of Botox
      make it particularly suitable for the treatment of Frey's Syndrome. We report our
      experience.

PMID- 16892917
TI  - Audit of the management of patients admitted with community acquired pneumonia.
AB  - Community acquired pneumonia (CAP) is a major cause of morbidity and mortality
      worldwide. There is evidence that guidelines do guide and standardise management,
      but with less measurable effect on outcome. We prospectively audited the
      management of CAP in patients admitted to a Dublin hospital during the winter of
      2003/04. The main objective was to evaluate the quality of care for CAP using the
      BTS guidelines as a standard of management. 164 patients were admitted with CAP
      during the defined period. Guidelines for assessment of disease severity at
      presentation were followed in only 56 (34.1%) cases. Appropriate antibiotic
      therapy was instituted within 8 hours of presentation in 123 (75.0%) cases. The
      rate of use of a severity assessment score to stratify patients with CAP based on
      recognized guidelines is low in our hospital. Despite this, the overall mortality
      rate of 8.5% is comparable with previous results.

PMID- 16892918
TI  - Cervical screening history in patients with early stage carcinoma of the cervix.
AB  - This study aimed to examine whether a decade of heightened publicity on issues
      relating to cervical screening has changed the screening profile of women
      presenting with cervical cancer at the National Maternity Hospital. The screening
      history of 100 women diagnosed with early/surgically treated cervical cancer
      between 1998 and 2002 was compared with a similar study conducted in 1982 /1990.
      The percentage of women never screened was similar - 24 %( 2002) and 23% (1990).
      The interval between last recorded smear and diagnosis of disease was greater
      than 5 years in 45.6% and 41.7% respectively. Overall 60% of women in the recent
      period had either failed to avail of screening or were not screened within 5
      years of diagnosis compared with 64% in 1990. Multiparous women comprised 90% of
      the study group and 50% of those inadequately screened were attending their
      general practitioner on a regular basis - therefore affording a potential for
      opportunistic screening The current method of screening has failed in this group
      and has not improved in 10 years despite of increased population awareness and
      greater opportunities for screening than ever before and would support an
      argument for a National Screening Program.

PMID- 16892919
TI  - The hidden costs of IVF.
AB  - Whether the payment is personal or funded via a third party, IVF is expensive.
      Clinical and drug costs are known and if necessary can be budgeted for. But,
      indirect expenses involved in participation also need to be considered. In order
      to find out what these latter might be, women attending Human Assisted
      Reproduction Ireland at the Rotunda Hospital Dublin completed prospectively a
      detailed questionnaire on all likely areas of extra expense during a single IVF
      cycle from down-regulation to zygote transfer. Four groups participated, divided
      according to their distance from the clinic. Group A were within Dublin and Group
      B within a 50 mile radius. Group C were between a 50-130 mile radius and Group D
      a 130-200 mile radius. Mean levels of costs increased with distance:- Group A 104
      euros. to Group D 703 euros. Food, meals and accommodation were the main
      contributors. Travel time and time-off work also increased with distance. These
      were respectively, Group A to Group D 15hrs to 139hrs: 35hrs to 75hrs. The study
      demonstrates that significant extra expense in time and money can be spent in an
      IVF cycle over and above medical and drug costs. This must be advised prior to
      commencement. All other issues being equal, geographical location should be part
      of the decision as to which clinic to attend.

PMID- 16892920
TI  - Cost effectiveness of statin therapy for the primary prevention of coronary heart
      disease.
AB  - Cholesterol lowering statin therapy accounted for over 10% of total drug
      acquisition costs (87.5 million euros) under the Community Drugs Schemes in
      Ireland in 2004. Not surprisingly, the issue of value for money and cost
      effectiveness arises. Whilst statin therapy has proven cost effective in patients
      with established cardiovascular disease this is the first economic evaluation of
      statin therapy for primary prevention in the Irish healthcare setting. Using
      economic modelling techniques the incremental cost effectiveness of statin
      therapy in high risk individuals i.e. 10 year risk exceeding 15% ranged from
      17,900 euros per life year gained (LYG) to 33,800 euros/LYG under the GMS scheme.
      Corresponding figures for the Drug Payment scheme were 24,500 euros/ LYG to
      48,500 euros/LYG. All the statins could be considered cost effective i.e.
      threshold below 50,000 euros/LYG however atorvastatin proved the most cost
      effective statin in this pharmacoeconomic study.

PMID- 16892922
TI  - The role of endobronchial electrocautery in the management of malignant airway
      obstruction.
AB  - Bronchoscopy has evolved well beyond a simple look-see examination, with new
      interventional techniques becoming more commonly employed. So-called
      interventional bronchoscopy implies the use of bronchoscopy as a therapeutic, in
      addition to diagnostic, tool. We present 2 cases to illustrate the utility of one
      such interventional technique, tumour ablation by endobronchial electrocautery
      and snaring, in the management of airway obstruction by tumour. This procedure,
      performed via a flexible bronchoscope under local anaesthesia can spare patients
      time-consuming, expensive treatments with their attendant morbidity, and in some
      cases can be life-saving. There is minimal morbidity associated with this
      technique. It is anticipated that interventional bronchoscopy will continue to
      revolutionise management of such conditions in the future, and become a necessary
      facility in all pulmonary medicine units.

PMID- 16892921
TI  - Gender identity disorder.
AB  - Gender Identity Disorder (GID) is a relatively rare condition of atypical gender
      development in which there is a psychological perception of self as masculine or
      feminine which is incongruent with ones phenotype. GID replaced the term
      Transsexualism in DSM-IV in 1994. The demographics of GID in Ireland have not
      been established. Since 2000 we have received 52 referrals of individuals with
      confirmed GID to our endocrine service for consideration for hormonal treatment
      (HT). Of the 52 patients 45 have male to female (MTF) GID (mean age 38.9 years)
      and 7 have female to male (FTM) GID (mean age 30.7 years). The age at
      presentation in this group is approximately 9 years older than in international
      series for both MTF (39 years v 30yrs) and FTM (31 yrs v 22yrs). The karyotype
      where analysed has been normal for their phenotypic sex. Twenty-three of the
      patients had received HT prior to attending our clinic that in only one case had
      been prescribed by a specialist. A number of patients had obtained HT via the
      internet or from overseas sources without medical review. Eighteen of the
      patients have been or are married and 14 of the group have children. The scale of
      referrals confirms that GID exists in the Irish population to a significant
      degree. Thus an appropriate care pathway for people with the condition needs to
      be established. This will facilitate optimum medical management of the patient
      group and a coherent approach to the many difficult social issues faced
      individuals with this disorder.

PMID- 16892923
TI  - National guidelines for the management of HIV-1 in pregnancy.
AB  - Management of HIV-1 in pregnancy has reduced the mother-to-child-transmission
      (MTCT) rate from 25-30% to <2% in the developed world, including Ireland. In
      Ireland most HIV positive pregnant women are diagnosed through antenatal
      screening many of whom arrive here late in pregnancy. Geographic dispersal and
      subsequent involvement of obstetric units throughout the country has resulted in
      a need for clear, accessible management guidelines. The Irish Infection Society
      first published guidelines for the management of HIV-1 in pregnancy in 2001 (1).
      The updated guidelines became operational in January 2002 with some amendments in
      March 2003 and July 2004. These guidelines offer a broad management outline for
      HIV positive pregnant women. Ultimately, each woman is assessed individually by a
      multidisciplinary team and a careful plan is determined.

PMID- 16892924
TI  - PANDAS (Paediatric Autoimmune Neuropsychiatric Disorder Associated with
      Streptococcal Infection).
AB  - PANDAS (Paediatric Autoimmune Neuropsychiatric Disorder Associated with
      Streptococcal Infection) is a rare condition first described in 1998. It
      describes the presence of obsessive-compulsive disorder (OCD) or tics with an
      episodic course, and a temporal relationship to Group A beta haemolytic
      streptococcal infection (GABHS). Recurrent episodes can be disruptive and
      upsetting for a child, but the best way to treat the condition has yet to be
      established. Penicillin prophylaxis has not proved effective, and other therapies
      are experimental. There is some evidence in the literature to support the role of
      tonsillectomy in improving the condition. We report a case of a 6-year-old boy
      who presented with tic and hemi-chorea associated with GABHS throat infection. He
      had a recurrence of his symptoms associated with a further GABHS infection, but
      has had no further symptoms following tonsillectomy. This case report lends
      further evidence to the role of tonsillectomy in the management of PANDAS.

PMID- 16892925
TI  - Knowledge and usage of seat belts in an Irish pregnant population.

PMID- 16892926
TI  - Dystextia - a sign of the times?

PMID- 16892927
TI  - The aetiology of brachial plexus injury: what the paediatrician and obstetrician
      need to know.
AB  - The recognition of brachial plexus injury (BPI) after childbirth suggests to
      parents a causative rather than temporal relationship. This view is supported by
      textbooks of paediatrics, which state that: 1. "the mechanism of injury is a
      forceful separation of the head from the shoulder by lateral bending of the neck
      with simultaneous shoulder depression, during vaginal delivery"; and 2. "these
      injuries are due to traction on the brachial plexus during delivery."2 Although
      an obstetrician will talk to a parent when BPI occurs, the ongoing care of the
      child is within a mutidisciplinary team, where the paediatrician and obstetrician
      play leading roles. Parents will ask about aetiology, treatment and prognosis;
      but is the textbook explanation adequate? We illustrate the potential dilemma for
      the paediatrician and obstetrician through 2 cases of BPI and outline some data
      on BPI, which is not congruent with current paediatric texts.

PMID- 16892928
TI  - Intermittent catheterization in the rehabilitation setting: a comparison of clean
      and sterile technique.
AB  - OBJECTIVE: To compare the onset of symptomatic urinary tract infection in
      individuals with spinal cord injury in a rehabilitation setting who are
      randomized to clean or sterile intermittent catheterization technique. DESIGN:
      Randomized controlled design. SETTING: Spinal cord rehabilitation units in
      western Canada. SUBJECTS: Thirty-six patients with cervical spinal cord injuries
      requiring intermittent catheterization by nursing staff were recruited. None had
      a previous history of voiding dysfunction or urinary tract infections.
      INTERVENTIONS: Subjects were randomized to either clean or sterile intermittent
      catheterization technique. Protocols for both clean and sterile techniques were
      standardized and followed by nursing staff and caregivers. MAIN MEASURES: Primary
      outcome measure was symptomatic urinary tract infection as diagnosed by urine
      culture > or = 10(5) colony-forming units/mL, pyuria (> or =10 leukocytes on high
      power field), and accompanying symptoms. RESULTS: A total of 189 urine specimens
      from 36 subjects were cultured. Of the 36 subjects, 15 (43%) developed a
      symptomatic urinary tract infection: 6/16 (37%) from the clean group; 9/20 (45%)
      from the sterile group (P> 0.05). Mean time to onset for symptomatic urinary
      tract infection for the clean group was 3.0 (standard deviation (SD) 2.4) weeks
      and for the sterile group, 3.6 (SD 1.3) weeks (P> 0.05). The most common urinary
      organisms at onset of symptomatic urinary tract infection were Enterococcus
      species followed by Klebsiella. CONCLUSION: Clean intermittent catheterization in
      the rehabilitation setting does not appear to place the patient with spinal cord
      injury at increased risk for developing symptomatic urinary tract infection, and
      has significant cost and time saving benefits for the health care system, as well
      as enhancing the transition for the patient from rehabilitation to community.

PMID- 16892929
TI  - Strength training in adolescent learners with cerebral palsy: a randomized
      controlled trial.
AB  - OBJECTIVE: To evaluate the impact of an eight-week strength training program
      targeting multiple muscle groups using basic inexpensive free weights and
      resistance devices, on gait and perceptions of body image and functional
      competence. DESIGN: A randomized control trial. SETTING: A school for children
      with special needs in a disadvantaged suburb in Cape Town. SUBJECTS: Thirty-one
      independently ambulant senior learners with spastic cerebral palsy (19 males, 12
      females; aged 13-18 years; 15 diplegics and 16 hemiplegics). INTERVENTION: Eight
      week strength training programme in circuit format executed during school hours,
      one to three times per week for 40-60 min per session. Programmes were
      individually designed and included 8-12 exercises selected from a 28-station
      circuit to target upper and lower limbs and trunk. Twenty-one subjects took part
      in the strength training programme and were compared with 10 control subjects.
      MAIN OUTCOME MEASURES: Three-dimensional gait analysis and a questionnaire were
      used to evaluate the various parameters of gait and perceptions of body image and
      functional competence respectively. Results were analysed using repeated measures
      ANOVA and bootstrap analysis. RESULTS: The experimental group differed
      significantly from the control group for measure of crouch gait (sum of the
      ankle, knee and hip angles at midstance) (P= 0.05) and perceptions of body image
      (P= 0.01). Walking velocity, cadence and stride length as well as perceptions of
      functional ability did not change significantly after training. CONCLUSION:
      Participation in a school-based strength training programme targeting multiple
      muscle groups can lead to improved degree of crouch gait and improve perception
      of body image.

PMID- 16892930
TI  - The effect of rehabilitation service use on coping patterns over time among older
      adults with age-related vision loss.
AB  - OBJECTIVE: To enhance our understanding of coping and rehabilitation in the
      context of adaptation to disability by examining how coping may change over a two
      year time period, and how different vision rehabilitation services may affect
      coping over time. DESIGN: Longitudinal two-wave study (baseline and two-year
      follow-up). SETTING: Vision rehabilitation agency. SUBJECTS: Older adults with
      visual impairment. METHOD: In-person interviews using structured assessments of
      functional vision loss and functional disability, rehabilitation service use and
      coping strategies. RESULTS: Ninety-five people participated in both study waves.
      Findings showed change in patterns of coping over the two-year period of the
      study, as participants adjusted to living with age-related vision loss. Although
      instrumental coping was the only coping mode with evidence for average change (a
      decrease), affective and escape/distraction strategies showed individual
      variation in change over time. Rehabilitation use explained variance in coping at
      time 2 over and above impairment status and coping at time 1. Those who used a
      greater number of assistive aids between time points were likely to report more
      instrumental coping at time 2, and those who used counselling between time points
      were likely to report more affective coping at the two-year follow-up. Finally,
      those who used more optical aids were likely to report more escape/distraction
      coping at time 2, whereas those who saw a low vision specialist tended to report
      less of this type of coping over time. CONCLUSIONS: Findings suggest that
      rehabilitation interventions can affect coping patterns over time, and that
      direction and magnitude of such an effect may depend on the type of
      rehabilitation received.

PMID- 16892931
TI  - Six-minute walk test in adults with cerebral palsy. A study of reliability.
AB  - OBJECTIVE: To determine the reliability of a six-minute walk test in adults with
      cerebral palsy. DESIGN: Four repeated walk tests during two weeks. SETTING: The
      tests were conducted in a 40-m-long corridor at a rehabilitation centre for
      outpatients. SUBJECTS: Twenty-five adults (9 women and 16 men) with CP. Mean age
      36 (26-58) years. Twelve subjects walked with walking aids and 13 without.
      INTERVENTIONS: No intervention. MEASURES: The subjects were instructed to walk as
      far as possible for 6 min. The distance walked, heart rate and perceived exertion
      were assessed. RESULTS: Mean distances walked by the subjects in the four tests
      were 316, 336, 341 and 345 m. The repeatability between test 1 and the other
      tests was 66 m, and when the first walk test was excluded 40 m. The coefficient
      of variation (CV) between test 1 and the other tests varied between 7.1 and 8.7%,
      and when the first walk test was excluded between 3.7 and 4.5%. Intraclass
      correlation (ICC 1.1) was 0.97 in the four tests, and when the first walk test
      was excluded 0.99. Walking distance was longer (P<0.01) and varied less in
      subjects walking without walking aids (n = 13) compared with subjects using
      walking aids (n = 12). CONCLUSIONS: Six-minute walk test showed high reliability,
      with a repeatability of 40 m. One practice test is recommended, as the walking
      distance in the first test was significantly shorter (P<0.01) than the other
      three tests.

PMID- 16892932
TI  - Responsiveness of isokinetic dynamometry parameters, pain and activity level
      scores to evaluate changes in patients with capsulitis of the shoulder.
AB  - OBJECTIVE: To determine the responsiveness to change of isokinetic dynamometry of
      the shoulder and to compare this responsiveness with outcome measures of pain and
      activity level. DESIGN: Responsiveness was evaluated as the change in outcome
      after intra-articular steroid injection in patients with capsulitis of the
      shoulder. Effect sizes of all outcome measures, quantified as standardized
      response means, were compared. Relationships between change scores of shoulder
      function and activities were assessed. SUBJECTS: Ten patients with unilateral
      capsulitis of the shoulder. MAIN OUTCOME MEASURES: Muscle strength and active
      range of motion were measured by isokinetic dynamometry. We then calculated
      involved/uninvolved ratios of the maximal peak torques of abduction, adduction,
      external and internal rotation, active range of motion of abduction and external
      rotation. In addition, pain was scored using the numeric rating scale (NRS-101)
      and activity level was scored using the Shoulder Disability Questionnaire.
      RESULTS: The standardized response mean of all outcome parameters was equal to or
      greater than 0.8, except for active range of motion of abduction. No significant
      differences between the standardized response means were found. There is a
      significant correlation between the change scores of NRS-101 and Shoulder
      Disability Questionnaire. No significant correlations were found between the
      change scores of NRS-101 and Shoulder Disability Questionnaire on the one hand,
      and involved/ uninvolved ratios of peak torques and active range of motion on the
      other. CONCLUSIONS: Responsiveness of all outcome measures is good. Parameters of
      isokinetic dynamometry may provide additional information as compared with the
      usual outcome measures of pain and functional level.

PMID- 16892933
TI  - The relationship between depressive symptoms and shoulder mobility among older
      women: assessment at one year after breast cancer diagnosis.
AB  - OBJECTIVE: To examine the association between depressive symptoms and shoulder
      range of motion at one year after breast cancer diagnosis, controlling for
      patient characteristics, tumour stage and cancer therapy (surgery, axillary node
      dissection and radiation). DESIGN: Prospective trial of nurse case management
      involving 187 older women with complete data, age 60 years and older, newly
      diagnosed with breast cancer, from 1 November, 1993 to 31 October, 1996 in south
      eastern Texas. Depressive symptoms, sociodemographic characteristics and breast
      cancer treatment were measured at two months and shoulder range of motion at 12
      months. The relationship among the variables was evaluated with bivariate chi
      square statistics and logistic regression analysis. All logistic models also
      included a variable indicating whether or not the woman received nurse case
      management, to control for intervention status. RESULTS: Increasing depressive
      symptoms at baseline were associated with lower arm mobility at 12 months
      following breast cancer diagnosis. Each unit increase in depressive symptoms at
      baseline was associated with an 8% decreased odds of having full range of motion
      of the shoulder (odds ratio (OR) 0.92, 95% confidence interval (CI) 0.87, 0.97),
      after controlling for relevant patient and treatment factors. CONCLUSION(S):
      Older women with depressive symptoms have an elevated risk of not fully
      recovering shoulder mobility after being treated for breast cancer. Future
      studies are needed to assess benefits from early intervention with psychological
      and or physical interventions in the presence of depressive symptoms on shoulder
      mobility.

PMID- 16892934
TI  - Dynamic interactions between impairment and activity after stroke: examining the
      utility of decision analysis methods.
AB  - OBJECTIVE: To examine the utility of decision analysis methods for examining the
      dynamic nature of impairment-activity interactions following stroke. DESIGN:
      Decision analyses (Chi-squared Automatic Interaction Detector) of a prospective
      cohort study. SETTING: Community and institutional settings based on the location
      of participants three months after stroke. PARTICIPANTS: Individuals were
      recruited from consecutive admissions to a regional academic health center and
      were assessed three months after stroke (N= 67). MAIN OUTCOME MEASURES:
      Neurological impairment was measured with the National Institutes of Health
      Stroke Scale (NIHSS). Mobility, self-care and instrumental activities of daily
      living (instrumental ADL) performance were assessed with a performance
      observation measure, the Performance Assessment of Self-care Skills (PASS).
      Decision analysis methods were used to examine interactions between neurological
      impairments and activity outcomes. RESULTS: Unique neurological impairments were
      associated with each activity outcome (bowel and bladder urgency interacted with
      mobility; hand function interacted with self-care; mental functions interacted
      with instrumental ADL), and these findings are supported by previous studies. The
      predictive validity of mobility and self-care analyses was stronger than the
      instrumental ADL analyses. CONCLUSIONS: Decision analysis methods show promise
      for understanding dynamic impairment--activity interactions. This understanding
      may enhance methods for informing rehabilitation decisions.

PMID- 16892935
TI  - Attitudes to falls and injury prevention: what are the barriers to implementing
      falls prevention strategies?
AB  - OBJECTIVES: To ascertain the reasons for not taking up a fall or injury
      prevention strategy among older people who have sustained a fall and attended an
      emergency department. SUBJECTS: As part of another trial, we identified 60 people
      who attended the emergency department of a public hospital with a fall. MAIN
      MEASURES: Participants were interviewed to ascertain the reasons for not taking
      up a falls prevention strategy, their falls-related health state, and the
      likelihood of them undertaking a falls and injury prevention strategy. RESULTS: A
      total of 31 (52%) of the participants had considered falls prevention after their
      fall. There were high levels of reluctance to undertake a strategy with 43 (72%)
      reluctant to take exercise classes, 10 (59%) reluctant to cease psychotropic
      medications, 26 (43%) reluctant to have a home safety assessment and 17 (28%)
      reluctant to take osteoporotic medication. When asked specifically about taking
      up a strategy to prevent a worsening health state, 19 (63%) of participants would
      take up exercise, 17 (57%) a home safety assessment, 4 of the 17 (59%) already
      taking implicated medications would stop and 56 (93%) would begin osteoporotic
      medication. These decisions did not alter when the goal for treatment was to
      improve a much worse health state. In participants with a lower starting health
      state, home safety assessments were viewed more favourably. CONCLUSIONS: There
      were significant obstacles to the implementation of most falls prevention
      guidelines examined. Treatment for osteoporosis was more acceptable to
      participants than exercise classes, cessation of psychotropic medication, and
      having a home safety assessment. Osteoporosis treatment, which had the least
      resistance, also had the least impact on the participants' lifestyle.

PMID- 16892936
TI  - Activities of daily living and social activities in people with multiple
      sclerosis in Stockholm County.
AB  - OBJECTIVE: To describe independence in personal and instrumental activities of
      daily living (ADL), and frequency of social/lifestyle activities in a population
      based sample of people with multiple sclerosis in Stockholm. DESIGN: Population
      based survey. SETTING: Data collection in home environment. SUBJECTS: One hundred
      and sixty-six people with multiple sclerosis. INTERVENTIONS: Data were collected
      using measurements and structured interviews. MAIN MEASURES: Independence in ADL
      was assessed by the Barthel Index; independence in personal and instrumental ADL
      by the Katz Extended ADL Index; and frequency of social/lifestyle activities by
      the Frenchay Activities Index. RESULTS: The mean age was 51 +/- 12 years in the
      included 166 people with multiple sclerosis, of whom 71% (n = 118) were women.
      Fifty-two per cent (n = 85) were independent in personal ADL, 30% (n = 50) in
      instrumental ADL, and 35% (n = 57) had normal frequency of social/lifestyle
      activities. Most frequently affected ADL items were cleaning indoors and outdoors
      transportation (62%, n = 102) and the social/lifestyle items of household
      maintenance (59%, n = 97), walking outside (59%, n = 97), heavy housework (61%, n
      = 100), and gardening (68%, n = 112). CONCLUSIONS: ADL and social/lifestyle
      activities were affected in two-thirds of people with multiple sclerosis in
      Stockholm. The most affected items were items that could be classified as
      mobility-related and physically demanding, underlining the importance of
      developing and using evidence-based exercise treatments and rehabilitation to
      increase independence in people with multiple sclerosis in Stockholm.

PMID- 16892937
TI  - Introduction to SafetyNet: lessons learned from close calls in the OR.

PMID- 16892939
TI  - Best practices for preventing wrong site, wrong person, and wrong procedure
      errors in perioperative settings.

PMID- 16892938
TI  - Learning from stories--a pathway to patient safety.

PMID- 16892940
TI  - Best practices for preventing a retained foreign body.

PMID- 16892941
TI  - Best practices for fire prevention in perioperative settings.

PMID- 16892942
TI  - Best practices for safe medication administration.

PMID- 16892943
TI  - A lead user of instruments in science: John D. Roberts and the adaptation of
      nuclear magnetic resonance to organic chemistry, 1955-1975.
AB  - During the 1960s organic chemistry underwent a spectacular transformation as a
      result of the introduction of high-tech instruments. In this process, nuclear
      magnetic resonance (NMR) became an important analytical technique in organic
      chemistry. The theme of this essay is the relationship of Varian Associates of
      Palo Alto, California, the major manufacturer of NMR spectrometers up to the
      1970s, with one early and crucial user, the organic chemist John D. Roberts, who
      was based at the California Institute of Technology in Pasadena. Roberts's
      research and teaching contributed to the fast and smooth acceptance of NMR in
      organic chemistry. He embraced the role of mediator between the instrument
      manufacturer, which had expertise mainly in physics and electrical engineering,
      and the customers, who were mostly organic chemists. This essay focuses on the
      tactics used by Roberts and James N. Shoolery at Varian Associates to implement
      novel types of instrumentation and on the modes of cooperation between instrument
      manufacturer and academic scientist.

PMID- 16892944
TI  - Device physics vis-a-vis fundamental physics in Cold War America: the case of
      quantum optics.
AB  - Historians have convincingly shown the close ties U.S. physicists had with the
      military during the Cold War and have raised the question of whether this
      alliance affected the content of physics. Some have asserted that it distorted
      physics, shifting attention from fundamental problems to devices. Yet the papers
      of physicists in quantum electronics and quantum optics, fields that have been
      exemplary for those who hold the distortion thesis, show that the same scientists
      who worked on military devices simultaneously pursued fundamental and
      foundational topics. This essay examines one such physicist, Marlan O. Scully,
      with attention to both his extensive foundational studies and the way in which
      his applied and basic researches played off each other.

PMID- 16892946
TI  - Anaximander in context: new studies in the origins of Greek philosophy (Isis,
      2005, 96:422-424).

PMID- 16892945
TI  - Pictures of evolution and charges of fraud: Ernst Haeckel's embryological
      illustrations.
AB  - Comparative illustrations of vertebrate embryos by the leading nineteenth-century
      Darwinist Ernst Haeckel have been both highly contested and canonical. Though the
      target of repeated fraud charges since 1868, the pictures were widely reproduced
      in textbooks through the twentieth century. Concentrating on their first ten
      years, this essay uses the accusations to shed light on the novelty of Haeckel's
      visual argumentation and to explore how images come to count as proper
      representations or illegitimate schematics as they cross between the esoteric and
      exoteric circles of science. It exploits previously unused manuscripts to
      reconstruct the drawing, printing, and publishing of the illustrations that
      attracted the first and most influential attack, compares these procedures to
      standard practice, and highlights their originality. It then explains why, though
      Haeckel was soon accused, controversy ignited only seven years later, after he
      aligned a disciplinary struggle over embryology with a major confrontation
      between liberal nationalism--and Catholicism--and why the contested pictures
      nevertheless survived.

PMID- 16892949
TI  - The pleasure of dissent: a critical theory of psychotherapy as an emancipatory
      practice.
AB  - The intent of this paper is to examine the inherent contradictions in the
      practice of psychotherapy that, if left unexamined, ruin the emancipatory
      prospects that it holds. Critical theory and, more specifically, Jurgen Habermas'
      theory of communicative action is utilized as a starting point for
      reconceptualizing psychotherapy. This paper then establishes a phenomenological
      and ethical basis for solidarity despite the power differences and conflicting
      goals for therapists and clients. It draws heavily on a consideration of
      intersubjectivity and the self as fundamentally relational as conceived by
      theorists such as Schutz, Levinas, and Vygotsky. Through such an analysis
      psychotherapy will be constituted consciously as a free space for critique,
      dissent and action, allowing for a core experience of one's self as a source of
      power in the social field that will foster replication in society at large.

PMID- 16892948
TI  - Psychological trauma and fixed ideas in Pierre Janet's conception of dissociative
      disorders.
AB  - This article describes Janet's concept of psychological trauma and the formation
      of rigid thought complexes (fixed ideas). This concept forms the basis for
      Janet's functional nosology of the neuroses, and is related to his dynamic
      psychology of conduct or action. It can be viewed as an early self-regulation
      model, because it contains a stratified bio-, socio-, and psycho-genetic
      hierarchy of behavioral "tendencies" that produce a more or less adaptive act by
      means of two hypothesized intervening variables: psychological force and
      psychological tension. Fixed ideas are viewed within this framework as an outcome
      of deficient processes of adaptation to psychological trauma. The article closes
      by pointing out affinities between Janet's psychological concept and modern
      cognitive and behavioral therapies.

PMID- 16892950
TI  - Brief psychotherapy: a brief review.
AB  - During the last several decades, brief psychotherapeutic approaches to mental
      health treatment have become increasingly prevalent. This paper describes brief
      psychotherapy and provides a brief review of the relevant empirical literature.
      Therapists who are unfamiliar with brief psychotherapy will find that this paper
      provides a concise introduction to the essential processes and outcomes of this
      therapeutic approach.

PMID- 16892951
TI  - The therapeutic consultation: finding the patient.
AB  - The psychiatric consultation has not been adequately exploited as a therapeutic
      device. Although, the original abstinent model for psychodynamic psychotherapy
      has become more flexible, passive listening with interventions to elicit
      diagnostic "data" remains the prevailing mode in psychiatric consultation. In
      this paper I develop the idea of the consultation as an active process
      (Viederman, M., 2002) that engages the patient emotionally for therapeutic
      effect.

PMID- 16892952
TI  - Logotherapy as an adjunctive treatment for chronic combat-related PTSD: a meaning
      based intervention.
AB  - Combat-related Post-traumatic Stress Disorder (PTSD) is often highly debilitating
      and affects nearly all areas of psychosocial functioning. Veterans with PTSD re
      experience their traumas in the form of haunting intrusive memories, nightmares
      and flashbacks, and have chronic difficulty modulating arousal. As a way to cope
      with these symptoms, many survivors live isolated and avoidant lives, self
      medicate with alcohol and substances of abuse, and numb themselves to emotional
      experiences and relationships with family and friends. Additionally, many combat
      veterans report survivor guilt, depression, affect dysregulation, and an altered
      world view in which fate is seen as uncontrollable and life is viewed as devoid
      of meaning. In this report we describe the use of logotherapy (healing through
      meaning) for the treatment of combat-related PTSD

PMID- 16892953
TI  - A pilot study of psychiatry resident psychotherapy competency: the impact of
      resident attitude and demographics.
AB  - OBJECTIVE: In psychiatry education, psychotherapy knowledge, skills, and
      attitudes are new competency objectives. METHODS: Two faculty members
      independently ranked psychiatry residents for psychotherapy competency. A rank of
      1 indicated the most competency and a rank of 15 indicated the least competency
      for the resident psychotherapist. Several demographic and attitudinal variables
      of the residents were examined for relationships with psychotherapy competence.
      RESULTS: When the competency rankings of the two faculty members were compared,
      they demonstrated a high level of agreement (spearman r = 0.74, p = 0.0016). Of
      the variables studied, resident age (r = .61, p = .015) and personal attitude
      toward psychotherapy (S=29, p = .026) were significantly associated with
      psychotherapy competency. Both variables remained independently significant after
      statistical adjustment. CONCLUSIONS: Our study indicates that psychiatry resident
      attitude and age may influence psychotherapy competency. These markers for
      psychotherapy competency may assist training programs with resident selection
      parameters and may enhance psychotherapy educational strategies for residents
      predicted to require assistance in achieving competency.

PMID- 16892954
TI  - Pity, suffering, and psychotherapy.
AB  - Every day psychotherapists are called upon to assuage and give meaning to human
      suffering. This report examines the ways in which therapists' and patients'
      attitudes towards giving and receiving "pity" can advance or interfere with the
      realization of these goals. Clinical observations, introspective analyses,
      interviews, and questionnaires are used to investigate the following questions:
      What feelings and thoughts are encompassed by the state of pitying a person or an
      aspect of a person? What are the similarities and differences between pity and
      compassion? How do pity and empathy interact in the therapeutic situation? When
      is taking and showing pity therapeutically beneficial? Is pity a force that
      brings people together, or is it a way of distancing ourselves from those whom we
      regard as "other"? Based on the phenomena brought to light by investigating these
      questions, the author proposes that pity is an inevitable and integral component
      of our reactions to the ordeals suffered through by individuals facing tragic
      situations. As a background, an overview of the two radically different
      conceptions of pity that coexist in our culture is presented.

PMID- 16892955
TI  - Walter Reed to continue legacy at new location, general says.

PMID- 16892956
TI  - Medical civic assistance program helps Korengal Valley Afghans.

PMID- 16892957
TI  - Medical personnel finish North African humanitarian exercise.

PMID- 16892958
TI  - PHS Junior Officer Advisory Group: the future of the United States Public Health
      Service Commissioned Corps.

PMID- 16892959
TI  - Anesthesiologists are not always liable for acts of CRNAs.

PMID- 16892960
TI  - Stomach stapling botched: $4 million verdict upheld.

PMID- 16892961
TI  - MS: pt. complained of forced shaving of beard: VA terminated nurse for "patient
      abuse".

PMID- 16892962
TI  - Nurse alleged wrongful termination violated public policy.

PMID- 16892963
TI  - The population genetics of adaptation on correlated fitness landscapes: the block
      model.
AB  - Several recent theoretical studies of the genetics of adaptation have focused on
      the mutational landscape model, which considers evolution on rugged fitness
      landscapes (i.e., ones having many local optima). Adaptation in this model is
      characterized by several simple results. Here I ask whether these results also
      hold on correlated fitness landscapes, which are smoother than those considered
      in the mutational landscape model. In particular, I study the genetics of
      adaptation in the block model, a tunably rugged model of fitness landscapes.
      Considering the scenario in which adaptation begins from a high fitness wild-type
      DNA sequence, I use extreme value theory and computer simulations to study both
      single adaptive steps and entire adaptive walks. I show that all previous results
      characterizing single steps in adaptation in the mutational landscape model hold
      at least approximately on correlated landscapes in the block model; many entire
      walk results, however, do not.

PMID- 16892964
TI  - The phenotypic variance within plastic traits under migration-mutation-selection
      balance.
AB  - How phenotypic variances of quantitative traits are influenced by the
      heterogeneity in environment is an important problem in evolutionary biology. In
      this study, both genetic and environmental variances in a plastic trait under
      migration-mutation-stabilizing selection are investigated. For this, a linear
      reaction norm is used to approximate the mapping from genotype to phenotype, and
      a population of clonal inheritance is assumed to live in a habitat consisting of
      many patches in which environmental conditions vary among patches and
      generations. The life cycle is assumed to be selection-reproduction-mutation
      migration. Analysis shows that phenotypic plasticity is adaptive if correlations
      between the optimal phenotype and environment have become established in both
      space and/or time, and it is thus possible to maintain environmental variance
      (V(E)) in the plastic trait. Under the special situation of no mutation but
      maximum migration such that separate patches form an effective single-site
      habitat, the genotype that maximizes the geometric mean fitness will come to
      fixation and thus genetic variance (V(G)) cannot be maintained. With mutation
      and/or restricted migration, V(G) can be maintained and it increases with
      mutation rate but decreases with migration rate; whereas VE is little affected by
      them. Temporal variation in environmental quality increases V(G) while its
      spatial variance decreases V(G). Variation in environmental conditions may
      decrease the environmental variance in the plastic trait.

PMID- 16892965
TI  - Population demography and the evolution of helping behaviors.
AB  - Limited dispersal may favor the evolution of helping behaviors between relatives
      as it increases their relatedness, and it may inhibit such evolution as it
      increases local competition between these relatives. Here, we explore one way out
      of this dilemma: if the helping behavior allows groups to expand in size, then
      the kin-competition pressure opposing its evolution can be greatly reduced. We
      explore the effects of two kinds of stochasticity allowing for such deme
      expansion. First, we study the evolution of helping under environmental
      stochasticity that may induce complete patch extinction. Helping evolves if it
      results in a decrease in the probability of extinction or if it enhances the rate
      of patch recolonization through propagules formed by fission of nonextinct
      groups. This mode of dispersal is indeed commonly found in social species.
      Second, we consider the evolution of helping in the presence of demographic
      stochasticity. When fecundity is below its value maximizing deme size
      (undersaturation), helping evolves, but under stringent conditions unless
      positive density dependence (Allee effect) interferes with demographic
      stochasticity. When fecundity is above its value maximizing deme size
      (oversaturation), helping may also evolve, but only if it reduces negative
      density-dependent competition.

PMID- 16892966
TI  - Likelihood methods for detecting temporal shifts in diversification rates.
AB  - Maximum likelihood is a potentially powerful approach for investigating the tempo
      of diversification using molecular phylogenetic data. Likelihood methods
      distinguish between rate-constant and rate-variable models of diversification by
      fitting birth-death models to phylogenetic data. Because model selection in this
      context is a test of the null hypothesis that diversification rates have been
      constant over time, strategies for selecting best-fit models must minimize Type I
      error rates while retaining power to detect rate variation when it is present.
      Here I examine model selection, parameter estimation, and power to reject the
      null hypothesis using likelihood models based on the birth-death process. The
      Akaike information criterion (AIC) has often been used to select among
      diversification models; however, I find that selecting models based on the lowest
      AIC score leads to a dramatic inflation of the Type I error rate. When
      appropriately corrected to reduce Type I error rates, the birth-death likelihood
      approach performs as well or better than the widely used gamma statistic, at
      least when diversification rates have shifted abruptly over time. Analyses of
      datasets simulated under a range of rate-variable diversification scenarios
      indicate that the birth-death likelihood method has much greater power to detect
      variation in diversification rates when extinction is present. Furthermore, this
      method appears to be the only approach available that can distinguish between a
      temporal increase in diversification rates and a rate-constant model with nonzero
      extinction. I illustrate use of the method by analyzing a published phylogeny for
      Australian agamid lizards.

PMID- 16892967
TI  - Evolution of intrahost HIV-1 genetic diversity during chronic infection.
AB  - HIV-1 is one of the fastest evolving entities known. Given that census population
      sizes of HIV-1 within individuals are much greater than the inverse mutation
      rate, every possible single point mutation in the viral genome occurs each
      generation. This enormous capability to generate genetic variation allows for
      escape from immune surveillance and antiviral therapy. However, compared to this
      potential, populations of HIV-1 within individuals exhibit little genetic
      variation. This discrepancy between the known mutation rate of HIV-1 and the
      average level of genetic variation in the env gene observed in vivo is reflected
      in comparisons of the actual numbers of productively infected cells, estimated as
      10(7), and the effective population size, estimated as 10(3). Using approximate
      Bayesian computation, we evaluated several hypotheses based on a variety of
      selective and demographic processes to explain the low effective population size
      of HIV-1. Of the models we examined, the metapopulation model, in which HIV-1
      evolves within an individual as a large collection of small subpopulations
      subject to frequent migration, extinction, and recolonization, was most
      consistent with the observed levels of genetic variation and the average
      frequencies of those variants. The metapopulation model links previous studies of
      viral dynamics and population genetics.

PMID- 16892968
TI  - Experimental evolution of resistance in Paramecium caudatum against the bacterial
      parasite Holospora undulata.
AB  - Host-parasite coevolution is often described as a process of reciprocal
      adaptation and counter adaptation, driven by frequency-dependent selection. This
      requires that different parasite genotypes perform differently on different host
      genotypes. Such genotype-by-genotype interactions arise if adaptation to one host
      (or parasite) genotype reduces performance on others. These direct costs of
      adaptation can maintain genetic polymorphism and generate geographic patterns of
      local host or parasite adaptation. Fixation of all-resistant (or all-infective)
      genotypes is further prevented if adaptation trades off with other host (or
      parasite) life-history traits. For the host, such indirect costs of resistance
      refer to reduced fitness of resistant genotypes in the absence of parasites. We
      studied (co)evolution in experimental microcosms of several clones of the
      freshwater protozoan Paramecium caudatum, infected with the bacterial parasite
      Holospora undulata. After two and a half years of culture, inoculation of evolved
      and naive (never exposed to the parasite) hosts with evolved and founder
      parasites revealed an increase in host resistance, but not in parasite
      infectivity. A cross-infection experiment showed significant host clone-by
      parasite isolate interactions, and evolved hosts tended to be more resistant to
      their own (local) parasites than to parasites from other hosts. Compared to naive
      clones, evolved host clones had lower division rates in the absence of the
      parasite. Thus, our study indicates de novo evolution of host resistance,
      associated with both direct and indirect costs. This illustrates how interactions
      with parasites can lead to the genetic divergence of initially identical
      populations.

PMID- 16892969
TI  - The evolution of California's wild radish has resulted in the extinction of its
      progenitors.
AB  - If two previously isolated taxa mutually assimilate through hybridization and
      subsequent biparental introgression, and if their introgressed descendants have
      the same or higher fitness than their parents, then gene flow should result in
      the local extinction of parental taxa via replacement by hybrid derivatives.
      These dramatic events may occur rapidly, even in a few generations. Given the
      speed at which such extinction by hybridization may occur, it may be difficult to
      identify that the process has occurred. Thus, documented instances of extinction
      by hybridization are rare, and especially so for cases in which both parents are
      replaced by the hybrid lineage. Here we report morphological and allozyme
      evidence for the local extinction of two Raphanus species in California via
      replacement by their hybrid-derived descendants. The results from a greenhouse
      experiment demonstrate that California wild radishes have a specific combination
      of traits from their progenitors, and comparison of our results to that of an
      earlier report indicate that pure parental types are no longer present in the
      wild. Our results also show the hybrid-derived lineage has transgressive fruit
      weight compared to its parents. Allozyme analysis demonstrates that California
      wild radishes are derived from hybridization between the putative parental
      species. However, that analysis also demonstrates that California wild radish has
      now become an evolutionary entity separate from both of its parents. We suggest
      that the aggressive colonizing behavior of the hybrid-derived lineage probably
      results from a novel combination of parental traits, rather than genetic
      variability of the population per se.

PMID- 16892970
TI  - On the abundance of polyploids in flowering plants.
AB  - The wide distribution of polyploidy among plants has led to a variety of theories
      for the evolutionary advantages of polyploidy. Here we claim that the abundance
      of polyploidy may be the result of a simple ratcheting process that does not
      require evolutionary advantages due to the biological properties of organisms.
      The evolution of polyploidy is a one-way process in which chromosome number can
      increase but not decrease. Using a simple mathematical model, we show that
      average ploidal level within a plant lineage can continually increase to the
      levels observed today, even if there are ecological or physiological
      disadvantages to higher ploidy. The model allowed us to estimate the average net
      speciation and polyploidy rates for ten angiosperm genera. Based on these
      estimates, the model predicts distributions of ploidal levels statistically
      similar to those observed in nine of the 10 genera.

PMID- 16892971
TI  - Pollination intensity influences sex ratios in dioecious Rumex nivalis, a wind
      pollinated plant.
AB  - Determining the mechanisms governing sex-ratio variation in dioecious organisms
      represents a central problem in evolutionary biology. It has been proposed that
      in plants with sex chromosomes competition between pollen tubes of female- versus
      male-determining microgametophytes (certation) causes female-biased primary sex
      ratios. Experimental support for this hypothesis is limited and recent workers
      have cast doubt on whether pollen-tube competition can modify sex ratios in
      dioecious plants. Here we investigate the influence of variation in pollination
      intensity on sex ratios in Rumex nivalis, a wind-pollinated alpine herb with
      strongly female-biased sex ratios. In a garden experiment, we experimentally
      manipulated pollination intensity using three concentric rings of female
      recipient plants at different distances from a central group of male pollen
      donors. This design enabled us to test the hypothesis that increasing pollen load
      size, by intensifying gametophyte competition, promotes female-biased sex ratios
      in R. nivalis. We detected a significant decline in pollen load at successive
      distance classes with concomitant reductions in seed set. Sex ratios of progeny
      were always female biased, but plants at the closest distance to male donors
      exhibited significantly greater female bias than more distant plants. The amount
      of female bias was positively correlated with the seed set of inflorescences.
      Hand pollination of stigmas resulted in approximately 100-fold higher stigmatic
      pollen loads than wind-pollinated stigmas and produced exceptionally female
      biased progenies (female frequency = 0.96). Our results are the first to
      demonstrate a functional relation between stigmatic pollen capture, seed set, and
      sex ratio and suggest that certation can contribute towards female-biased sex
      ratios in dioecious plants.

PMID- 16892973
TI  - Phylogenetic analysis of the Cardini group of Drosophila with respect to changes
      in pigmentation.
AB  - Phenotypic variability is the engine that drives future diversification with the
      expectation that polymorphic ancestors give rise to descendants harboring a
      subset of the ancestral variation. Here we examine evolutionary transitions from
      polymorphism to monomorphism in a visually striking New World radiation of fruit
      flies, the Drosophila cardini group. This group is distributed across the
      Americas and the Caribbean islands and exhibits a wide spectrum of abdominal
      pigmentation variation. Specifically, the D. dunni subgroup consists of Caribbean
      island endemics, each of which is monomorphic for its pigmentation pattern, with
      an interspecific cline of pigmentation across the islands. The D. cardini
      subgroup consists of American continental species with wide-ranging distributions
      and intraspecifically variable abdominal pigmentation. We determined the
      phylogeny of 18 species and subspecies using three nuclear and three
      mitochondrial regions analyzed with maximum parsimony, maximum likelihood, and
      Bayesian methods. The topology produced from a combined dataset exhibited high
      support values at all nodes, and differed from earlier phylogenetic hypotheses
      based on polytene chromosome inversion patterns and isozyme data. We find that
      the D. dunni subgroup species, with the exception of D. belladunni, are derived
      from a single source not of direct South American origin and their dispersal
      across the islands of the Caribbean does not follow a simple stepping-stone
      model. Morphological changes in pigmentation across the island species are
      incongruent with the colonization history of the group indicating that natural
      selection may have played a role in the determination of this character. Finally,
      we demonstrate that monomorphic species have arisen independently from
      polymorphic ancestors two to three times.

PMID- 16892972
TI  - Fitness and genetic architecture of parent and hybrid willows in common gardens.
AB  - Models of hybrid zone dynamics incorporate different patterns of hybrid fitness
      relative to parental species fitness. An important but understudied source of
      variation underlying these fitness differences is the environment. We
      investigated the performance of two willow species and their F1, F2, and
      backcross hybrids using a common-garden experiment with six replicated gardens
      that differed in soil moisture. Aboveground biomass, catkin production, seed
      production per catkin, and seed germination rate were significantly different
      among genetic classes. For aboveground biomass and catkin production, hybrids
      generally had intermediate or inferior performance compared to parent species.
      Salix eriocephala had the highest performance for all performance measures, but
      in two gardens F, plants had superior or equal performance for aboveground
      biomass and female catkin production. Salix eriocephala and backcrosses to S.
      eriocephala had the highest numbers of filled seeds per catkin and the highest
      estimates of total fitness in all gardens. Measures of filled seeds per catkin
      and germination rate tend to support the model of endogenous hybrid unfitness,
      and these two measures had major effects on estimates of total seed production
      per catkin. We also estimated how the two willow species differ genetically in
      these fitness measures using line cross analysis. We found a complex genetic
      architecture underlying the fitness differences between species that involved
      additive, dominance, and epistatic genetic effects for all fitness measures. The
      environment was important in the expression of these genetic differences, because
      the type of epistasis differed among the gardens for above-ground biomass and for
      female catkin production. These findings suggest that fine-scale environmental
      variation can have a significant impact on hybrid fitness in hybrid zones where
      parents and hybrids are widely interspersed.

PMID- 16892974
TI  - Effects of natural and sexual selection on adaptive population divergence and
      premating isolation in a damselfly.
AB  - The relative strength of different types of directional selection has seldom been
      compared directly in natural populations. A recent meta-analysis of phenotypic
      selection studies in natural populations suggested that directional sexual
      selection may be stronger in magnitude than directional natural selection,
      although this pattern may have partly been confounded by the different time
      scales over which selection was estimated. Knowledge about the strength of
      different types of selection is of general interest for understanding how
      selective forces affect adaptive population divergence and how they may influence
      speciation. We studied divergent selection on morphology in parapatric, natural
      damselfly (Calopteryx splendens) populations. Sexual selection was stronger than
      natural selection measured on the same traits, irrespective of the time scale
      over which sexual selection was measured. Visualization of the fitness surfaces
      indicated that population divergence in overall morphology is more strongly
      influenced by divergent sexual selection rather than natural selection. Courtship
      success of experimental immigrant males was lower than that of resident males,
      indicating incipient sexual isolation between these populations. We conclude that
      current and strong sexual selection promotes adaptive population divergence in
      this species and that premating sexual isolation may have arisen as a correlated
      response to divergent sexual selection. Our results highlight the importance of
      sexual selection, rather than natural selection in the adaptive radiation of
      odonates, and supports previous suggestions that divergent sexual selection
      promotes speciation in this group.

PMID- 16892975
TI  - Multilocus analyses of admixture and introgression among hybridizing Heliconius
      butterflies.
AB  - Introgressive hybridization is an important evolutionary process and new
      analytical methods provide substantial power to detect and quantify it. In this
      study we use variation in the frequency of 657 AFLP fragments and DNA sequence
      variation from 15 genes to measure the extent of admixture and the direction of
      interspecific gene flow among three Heliconius butterfly species that diverged
      recently as a result of natural selection for Miillerian mimicry, and which
      continue to hybridize. Bayesian clustering based on AFLP genotypes correctly
      delineated the three species and identified four H. cydno, three H. pachinus, and
      three H. melpomene individuals that were of mixed ancestry. Gene genealogies
      revealed substantial shared DNA sequence variation among all three species and
      coalescent simulations based on the Isolation with Migration (IM) model pointed
      to interspecific gene flow as its cause. The IM simulations further indicated
      that interspecific gene flow was significantly asymmetrical, with greater gene
      flow from H. pachinus into H. cydno (2Nm = 4.326) than the reverse (2Nm = 0.502),
      and unidirectional gene flow from H. cydno and H. pachinus into H. melpomene (2Nm
      = 0.294 and 0.252, respectively). These asymmetries are in the directions
      expected based on the genetics of wing patterning and the probability that
      hybrids of various phenotypes will survive and reproduce in different mimetic
      environments. This empirical demonstration of extensive interspecific gene flow
      is in contrast to a previous study which found little evidence of gene flow
      between another pair of hybridizing Heliconius species, H. himera and H. erato,
      and it highlights the critical role of natural selection in maintaining species
      diversity. Furthermore, these results lend support to the hypotheses that
      phenotypic diversification in the genus Heliconius has been fueled by
      introgressive hybridization and that reinforcement has driven the evolution of
      assortative mate preferences.

PMID- 16892976
TI  - Evolution of intrinsic growth rate: metabolic costs drive trade-offs between
      growth and swimming performance in Menidia menidia.
AB  - There is strong evidence that genetic capacity for growth evolves toward an
      optimum rather than an absolute maximum. This implies that fast growth has a cost
      and that trade-offs occur between growth and other life-history traits, but the
      fundamental mechanisms are poorly understood. Previous work on the Atlantic
      silverside fish Menidia menidia has demonstrated a trade-off between growth and
      swimming performance. We hypothesize that the trade-off derives from the
      competing metabolic demands associated with growth and swimming activity. We
      tested this by measuring standard metabolic rate (M(STD)), maximum sustainable
      metabolic rate (M(ACT)) and metabolic scope of laboratory-reared silversides
      originating from two geographically distinct populations with well-documented
      differences in genetic capacity for growth. The fast-growth genotype had a
      significantly greater M(STD) than the slow-growth genotype, but a similar MACT
      when swum to near exhaustion. The scope for activity of the fast-growth genotype
      was lower than that of the slow-growth genotype. Furthermore, the fast-growth
      genotype eats larger meals, thereby incurring a greater postprandial oxygen
      demand. We conclude that a metabolic trade-off occurs between growth and other
      metabolic demands and that this trade-off provides a general mechanism underlying
      the evolution of growth rate.

PMID- 16892977
TI  - Genetic population structure and call variation in a passerine bird, the satin
      bowerbird, Ptilonorhynchus violaceus.
AB  - Geographic variation in vocalizations is widespread in passerine birds, but its
      origins and maintenance remain unclear. One hypothesis to explain this variation
      is that it is associated with geographic isolation among populations and
      therefore should follow a vicariant pattern similar to that typically found in
      neutral genetic markers. Alternatively, if environmental selection strongly
      influences vocalizations, then genetic divergence and vocal divergence may be
      disassociated. This study compared genetic divergence derived from 11
      microsatellite markers with a metric of phenotypic divergence derived from male
      bower advertisement calls. Data were obtained from 16 populations throughout the
      entire distribution of the satin bowerbird, an Australian wet-forest-restricted
      passerine. There was no relationship between call divergence and genetic
      divergence, similar to most other studies on birds with learned vocalizations.
      Genetic divergence followed a vicariant model of evolution, with the
      differentiation of isolated populations and isolation-by-distance among
      continuous populations. Previous work on Ptilonorhynchus violaceus has shown that
      advertisement call structure is strongly influenced by the acoustic environment
      of different habitats. Divergence in vocalizations among genetically related
      populations in different habitats indicates that satin bowerbirds match their
      vocalizations to the environment in which they live, despite the homogenizing
      influence of gene flow. In combination with convergence of vocalizations among
      genetically divergent populations occurring in the same habitat, this shows the
      overriding importance that habitat-related selection can have on the
      establishment and maintenance of variation in vocalizations.

PMID- 16892978
TI  - Evolutionary persistence of phenotypic integration: influence of developmental
      and functional relationships on complex trait evolution.
AB  - Examination of historical persistence of integration patterns provides an
      important insight into understanding the origin and evolution of complex traits.
      Specifically, the distinct effects of developmental and functional integration on
      the evolution of complex traits are often overlooked. Because patterns of
      functional integration are commonly shaped by selection exerted by the external
      environment, whereas patterns of developmental integration can be determined by
      relatively environment-independent selection for developmental homeostasis,
      examination of historical persistence of morphological integration patterns among
      species should reveal the relative importance of current selection in the
      evolution of complex traits. We compared historical persistence of integration
      patterns produced by current developmental versus ecological requirements by
      examining the evolution of complex mandibular structures in nine species of
      soricid shrews. We found that, irrespective of phylogenetic relatedness of
      species, patterns of developmental and functional integration were highly
      concordant, suggesting that strong selection for developmental homeostasis favors
      concordant channeling of both internal and external variation. Overall, our
      results suggest that divergence in mandible shape among species closely follows
      variation in functional demands and ecological requirements regardless of
      phylogenetic relatedness among species.

PMID- 16892979
TI  - Genetic variation for outcrossing among Caenorhabditis elegans isolates.
AB  - The evolution of breeding systems results from the existence of genetic variation
      and selective forces favoring different outcrossing rates. In this study we
      determine the extent of genetic variation for characters directly related to
      outcrossing, such as male frequency, male mating ability, and male reproductive
      success, in several wild isolates of the nematode Caenorhabditis elegans. This
      species is characterized by an androdioecious breeding system in which males
      occur with hermaphrodites that can either self-fertilize or outcross with males.
      We find genetic variation for all characters measured, but also find that
      environmental variation is a large fraction of the total phenotypic variance. We
      further determine the existence of substantial genetic variation for population
      competitive performance in several laboratory environments. However, these
      measures are uncorrelated with outcrossing characters. The data presented here
      contribute to an understanding of male maintenance in natural populations through
      their role in outcrossing.

PMID- 16892980
TI  - Invertebrate predation selects for the loss of a morphological antipredator
      trait.
AB  - Antagonistic selection by different predators has been suggested to underlie
      variation in morphological antipredator traits among and within species. Direct
      empirical proof is equivocal, however, given the potential interrelationships of
      morphological and behavioral traits. Here, we tested whether spines in larvae of
      the dragonfly Leucorrhinia caudalis, which are selected for by fish predators,
      are selected against by invertebrate aeshnid predators. Using a manipulative
      approach by cutting spines instead of making comparisons among species or
      inducing spines, we were able to decouple the presence of spines from other
      potentially covarying morphological antipredator traits. Results showed survival
      selection for the loss of spines imposed by invertebrate predation. Moreover,
      spined and nonspined larval L. caudalis did not differ in the key antipredator
      behaviors, activity level, and escape burst swimming speed. The observed higher
      mortality of spined larvae can therefore be directly linked to selection by
      aeshnid predation against spines.

PMID- 16892981
TI  - Comparative phylogenetic analysis of male alternative reproductive tactics in ray
      finned fishes.
AB  - Using comparative phylogenetic analysis, we analyzed the evolution of male
      alternative reproductive tactics (MARTs) in ray-finned fishes (Actinopterygii).
      Numerous independent origins for each type of MART (involving sneaker males,
      female mimics, pirates, and satellite males) indicate that these behaviors have
      been highly labile across actinopterygiian evolution, consistent with a previous
      notion that convergent selection in fishes can readily mold the underlying suites
      of reproductive hormones into similar behaviors. The evolutionary appearance of
      MARTs was significantly correlated with the presence of sexually selected traits
      in bourgeois males (P = 0.001) but not with the presence of male parental care.
      This suggests that MARTs often arise from selection on some males to circumvent
      bourgeois male investment in mate monopolization, rather than to avoid male brood
      care per se. We found parsimony evidence for an evolutionary progression of MARTs
      wherein sneaking is usually the evolutionary precursor to the presumably more
      complex MARTs of female mimicry and cooperative satellite behavior. Nest piracy
      appears not to be part of this evolutionary progression, possibly because its
      late onset in the life cycle of most ray-finned fishes reduces the effects of
      selection on this reproductive tactic.

PMID- 16892983
TI  - Spatial coding in two dimensions.
AB  - There has been growing interest in exploring human performance for situations in
      which stimuli and/or responses vary along both horizontal and vertical
      dimensions. Earlier studies indicated that there is a prevalence of the
      horizontal dimension over the vertical dimension in the spatial codes that are
      used for response selection. We review evidence about spatial coding for 2-D
      stimulus-response sets and accounts that have been proposed for explaining how it
      takes place. Particular attention is devoted to the relative salience account,
      which provides the most comprehensive explanation of 2-D spatial coding. We also
      evaluate the influence of speed of spatial code formation, number of reference
      frames, and learning on subjects' performance in 2-D tasks.

PMID- 16892984
TI  - Memory for facial expressions: the power of a smile.
AB  - Faces with expressions (happy, surprise, anger, fear) were presented at study.
      Memory for facial expressions was tested by presenting the same faces with
      neutral expressions and asking participants to determine the expression that had
      been displayed at study. In three experiments, happy expressions were remembered
      better than other expressions. The advantage of a happy face was observed even
      when faces were inverted (upside down) and even when the salient perceptual
      feature (broad grin) was controlled across conditions. These findings are couched
      in terms of source monitoring, in which memory for facial expressions reflects
      encoding of the dispositional context of a prior event.

PMID- 16892985
TI  - Do the upright eyes have it?
AB  - Eye contact is crucial for social communication. A perceived direct gaze
      facilitates detection, whereas face inversion diminishes this facilitative effect
      (Senju, Hasegawa, & Tojo, 2005). In the present study, we adopted a visual search
      paradigm to investigate why a direct gaze facilitates detection in an upright
      face, but not in an upside-down face. Upright eyes were found to facilitate
      detection even when other parts of the face were inverted or absent, whereas
      inverted eyes had no effect on search performance. A critical role for the
      morphological information of upright eyes, which can be distorted by "eye
      inversion," in direct gaze processing is suggested.

PMID- 16892982
TI  - Weaving the fabric of social interaction: articulating developmental psychology
      and cognitive neuroscience in the domain of motor cognition.
AB  - In this article, we bring together recent findings from developmental science and
      cognitive neuroscience to argue that perception-action coupling constitutes the
      fundamental mechanism of motor cognition. A variety of empirical evidence
      suggests that observed and executed actions are coded in a common cognitive and
      neural framework, enabling individuals to construct shared representations of
      self and other actions. We review work to suggest that such shared
      representations support action anticipation, organization, and imitation. These
      processes, along with additional computational mechanisms for determining a sense
      of agency and behavioral regulation, form the fabric of socialinteraction. In
      addition, humans possess the capacity to move beyond these basic aspects of
      action analysis to interpret behavior at a deeper level, an ability that may be
      outside the scope of the mirror system. Understanding the nature of shared
      representations from the vantage point of developmental and cognitive science and
      neuroscience has the potential to inform a range of motor and social processes.
      This perspective also elucidates intriguing new directions and research questions
      and generates specific hypotheses regarding the impact of early disorders (e.g.,
      developmental movement disorders) on subsequent action processing.

PMID- 16892986
TI  - Posing for success: clenching a fist facilitates approach.
AB  - A clenched fist is a gesture often seen both within and outside sports that seems
      to communicate success or to function in self-encouragement or the encouragement
      of others. This "encouragement gesture" involves the contraction of forearm
      flexors, similar to the grasping action that is part of acquisitive approach
      actions. This gesture may be part of a physiological feedback mechanism that
      functions to increase or sustain levels of approach in challenging situations by
      signaling the sufficiency of resources (muscle strength). Here we show that for
      pleasant but not unpleasant words, subjects were faster in categorizing words
      while contracting their forearm flexors rather than their forearm tensors. This
      effect dissipated during the first minute of performance, which may reflect
      habituation of interoceptive feedback. The data further suggest that the effect
      is larger when experimenter and subject are of opposite sexes. The facilitated
      responding to pleasant stimuli suggests that contraction of the forearm flexors
      promotes approach.

PMID- 16892987
TI  - Hedonic contrast and condensation: good stimuli make mediocre stimuli less good
      and less different.
AB  - Loud sounds make soft sounds softer (contrast) and also make them less
      discriminable (which we call condensation). We report on parallel phenomena in
      hedonics: Good stimuli reduce the pleasantness of less good stimuli, and also
      reduce people's preferences among the less good stimuli. In Experiment 1,
      subjects rated the pleasantness of fruit juices diluted to approximate hedonic
      neutrality. Subjects who had just previously drunk and rated some good-tasting
      full-strength juices rated thediluted juices lower than did subjects who had not
      (hedonic contrast). In Experiment 2, subjects drank pairs of diluted juices and
      rated their preference for one juice over the other. Subjects who had just
      previously drunk and rated pairs of full-strength juices gave lower preference
      ratings between the diluted juices than did subjects who had not (condensation).
      Thus the same stimulus set produced contrast in Experiment 1 and condensation in
      Experiment 2, paralleling results in loudness.

PMID- 16892988
TI  - Smell your way back to childhood: autobiographical odor memory.
AB  - This study addressed age distributions and experiential qualities of
      autobiographical memories evoked by different sensory cues. Ninety-three older
      adults were presented with one of three cue types (word, picture, or odor) and
      were asked to relate any autobiographical event for the given cue. The main aims
      were to explore whether (1) the age distribution of olfactory-evoked memories
      differs from memories cued by words and pictures and (2) the experiential
      qualities of the evoked memories vary over the different cues. The results showed
      that autobiographical memories triggered by olfactory information were older than
      memories associated with verbal and visual information. Specifically, most odor
      cued memories were located to the first decade of life (<10 years), whereas
      memories associated with verbal and visual cues peaked in early adulthood (11-20
      years). Also, odor-evoked memories were associated with stronger feelings of
      being brought back in time and had been thought of less often than memories
      evoked by verbal and visual information. This pattern of findings suggests that
      odor-evoked memories may be different from other memory experiences.

PMID- 16892989
TI  - Within-category feature correlations and Bayesian adjustment strategies.
AB  - To the extent that categories inform judgments about items, the accuracy with
      which categories capture the statistical structure of experience should affect
      judgment accuracy. The authors argue that representations of feature correlations
      can serve as Bayesian priors, increasing the accuracy of stimulus estimates by
      decreasing variability. Participants viewed a series of objects that varied on
      two dimensions that were either uncorrelated or correlated. They estimated each
      item by manipulating a response object to make it match the presented stimulus.
      Subsequent classification and feature-inference tasks indicated that the
      correlation was detected. The pattern of variability in recollections of stimuli
      suggested that the feature correlation informed estimates as predicted by a
      Bayesian model of category effects on memory.

PMID- 16892990
TI  - Sorting out categories: incremental learning of category structure.
AB  - Two experiments examine how inferences might promote unsupervised and incremental
      category learning. Many categories have members related through overall
      similarity (e.g., a family resemblance structure) rather than by a defining
      feature. However, when people are asked to sort category members in a category
      construction task, they often do so by partitioning on a single feature. Starting
      from an earlier result showing that pairwise inferences increase family
      resemblance sorting (Lassaline & Murphy, 1996), we examine how these inferences
      lead to learning the family resemblance structure. Results show that the category
      structure is learned incrementally. The pairwise inferences influence
      participants' weightings of feature pairs that were specifically asked about,
      which in turn affects their sorting. The sorting then allows further learning of
      the categorical structure. Thus, the inferences do not directly lead learners to
      the family resemblance structure, but they do provide a foundation to build on as
      the participants make additional judgments.

PMID- 16892991
TI  - Infants' sensitivity to uniform connectedness as a cue for perceptual
      organization.
AB  - A new grouping principle, uniform connectedness (UC), has been posited to be a
      basic organizer of visual pattern information, one that takes precedence over
      other, more classic grouping principles (Palmer & Rock, 1994), but its
      ontogenetic origins have not previously been investigated. We examined whether 3-
      to 4-month-olds and 6- to 7-month-olds utilize UC to organize static two
      dimensional displays. Infants habituated to uniformly connected patterns
      exhibited a novelty preference for disconnected element patterns, whereas those
      without any habituation failed to exhibit a preference. The results indicate that
      infants are sensitive to UC as a cue for perceptual organization. Prior studies
      indicate that some Gestalt principles (e.g., common movement) are functional
      during the first half year of life, but that other principles (e.g., form
      similarity) are less readily available. The present finding showing that young
      infants are sensitive to UC points to the foundational nature of this cue and
      adds to an emerging body of evidence indicating that at least some of the
      mechanisms believed to produce perceptual organization in adults are already
      operational in the first months of life.

PMID- 16892992
TI  - Generalization in perceptual learning for speech.
AB  - Lexical context strongly influences listeners' identification of ambiguous
      sounds. For example, a sound midway between /f/ and /s/ is reported as /f/ in
      "sheri_," but as /s/ in "Pari_." Norris, McQueen, and Cutler (2003) have
      demonstrated that after hearing such lexically determined phonemes, listeners
      expand their phonemic categories to include more ambiguous tokens than before. We
      tested whether listeners adjust their phonemic categories for a specific speaker.
      Do listeners learn a particular speaker's "accent"? Similarly, we examined
      whether perceptual learning is specific to the particular ambiguous phonemes that
      listeners hear, or whether the adjustments generalize to related sounds.
      Participants heard ambiguous /d/ or /t/ phonemes during a lexical decision task.
      They then categorized sounds on /d/-/t/ and /b/-/p/ continua, either in the same
      voice that they had heard for lexical decision, or in a different voice.
      Perceptual learning generalized across both speaker and test continua: Changes in
      perceptual representations are robust and broadly tuned.

PMID- 16892993
TI  - Verbal overshadowing of perceptual discrimination.
AB  - We examined effects of verbal interference on a perceptual discrimination task.
      Participants were presented with a series of faces, described (or did not
      describe) an additional face, and then made face/ nonface decisions to both the
      original faces and new faces, intermingled with nonfaces. This enabled us to
      examine the effect of making a verbal description, relative to an unrelated
      filler task in a control condition, on the perceptual discrimination of faces
      seen for the first time and faces encountered previously, and also on repetition
      priming (i.e., the facilitative effect of an encounter with a stimulus on
      subsequent processing of the same stimulus). Verbalization interfered with
      performance on both new and studied faces, but it did not interfere with priming.
      We argue that verbalization encouraged a relatively long-lasting shift (over a
      number of trials) toward greater visual processing of individual facial features
      at the expense of more global visual processing, which is generally beneficial
      for the recognition of faces and important for discriminating faces from nonfaces
      in the face decision task.

PMID- 16892995
TI  - Spatial updating relies on an egocentric representation of space: effects of the
      number of objects.
AB  - Models of spatial updating attempt to explain how representations of spatial
      relationships between the actor and objects in the environment change as the
      actor moves. In allocentric models, object locations are encoded in an external
      reference frame, and only the actor's position and orientation in that reference
      frame need to be updated. Thus, spatial updating should be independent of the
      number of objects in the environment (set size). In egocentric updating models,
      object locations are encoded relative to the actor, so the location of each
      object relative to the actor must be updated as the actor moves. Thus, spatial
      updating efficiency should depend on set size. We examined which model better
      accounts for human spatial updating by having people reconstruct the locations of
      varying numbers of virtual objects either from the original study position or
      from a changed viewing position. In consistency with the egocentric updating
      model, object localization following a viewpoint change was affected by the
      number of objects in the environment.

PMID- 16892994
TI  - Cross-species differences in color categorization.
AB  - Berlin and Kay (1969) found systematic restrictions in the color terms of the
      world's languages and were inclined to look to the primate visual system for
      their origin. Because the visual system does not provide adequate
      neurophysiological discontinuities to supply natural color category boundaries,
      and because recent evidence points to a linguistic origin (Davidoff, Davies, &
      Roberson, 1999), a new approach was used to investigate the controversial issue
      of the origin of color categories. Baboons and humans were given the same task of
      matching-to-sample colors that crossed the blue/green boundary. The data and
      consequent modeling were remarkably clear-cut. All human subjects matched our
      generalization probe stimuli as if to a sharp boundary close to the midpoint
      between their training items. Despite good color discrimination, none of the
      baboons showed any inclination to match to a single boundary but rather responded
      with two boundaries close to the training stimuli. The data give no support to
      the claim that color categories are explicitly instantiated in the primate color
      vision system.

PMID- 16892996
TI  - Effects of top-down guidance and singleton priming on visual search.
AB  - Recent literature suggests that observers can use advance knowledge of the target
      feature to guide their search but fail to do so whenever the target is reliably a
      singleton. Instead, they engage in singleton-detection mode--that is, they search
      for the most salient object. In the present study, we aimed to test the notion of
      a default salience-based search mode. Using several measures, we compared search
      for a known target when it is always a singleton (fixed-singleton search)
      relative to when it is incidentally a singleton (multiple-target search). We
      examined the relative contributions of strategic factors (knowledge that the
      target is a singleton) and intertrial repetition effects (singleton priming, or
      the advantage of responding to a singleton target if the target on the previous
      trial had also been a singleton). In two experiments, singleton priming
      eliminated all the differences in performance between fixed-singleton and
      multiple-target search, suggesting that search for a known singleton may be
      feature based rather than salience based.

PMID- 16892997
TI  - The effects of memory load on the time course of inhibition of return.
AB  - Inhibition of return (IOR) refers to a processing disadvantage at a recently
      attended location. It is generally agreed that when elicited in a cue-target
      task, IOR will not be apparent until attention is disengaged from the originally
      cued location and returned to a neutral state. Here we test the hypothesis that
      when such disengagement is dependent on endogenous control, a secondary task that
      taxes working memory capacity should delay the appearance of IOR. Participants
      were given a six-item verbal working memory load prior to the peripheral cue in a
      cue-target detection task. Consistent with the hypothesis, the appearance of IOR
      was delayed on trials for which participants had to hold information in working
      memory. Converging evidence was derived from a second experiment in which the
      time course of IOR's appearance, when we added a central cue to exogenously
      remove attention from the peripheral cue, was unaffected by the memory load.

PMID- 16892998
TI  - The failure to detect tactile change: a tactile analogue of visual change
      blindness.
AB  - A large body of empirical research now shows that people are surprisingly poor at
      detecting significant changes in visually presented scenes. This phenomenon is
      known as change blindness in vision. A similar phenomenon occurs in audition, but
      to date no such effect has been documented in touch. In the present study, we
      explored the ability of people to detect changes introduced between two
      consecutively presented vibrotactile patterns presented over the body surface.
      The patterns consisted of two or three vibrotactile stimuli presented for 200
      msec. The position of one of the vibrotactile stimuli composing the display was
      repeatedly changed (alternating between two different positions) on 50% of the
      trials, but the same pattern was presented repeatedly on the remaining trials.
      Three conditions were investigated: No interval between the patterns, an empty
      interval between the patterns, and a masked interval between the patterns. Change
      detection was near perfect in the no-interval block. Performance deteriorated
      somewhat in the empty-interval block, but by far the worst change detection
      performance occurred in the masked-interval block. These results demonstrate that
      "change blindness" can also affect tactile perception.

PMID- 16892999
TI  - See what you've done! Active touch affects the number of perceived visual
      objects.
AB  - Previous research has shown that visual perception is affected by sensory
      information from other modalities. For example, sound can alter the visual
      intensity or the number of visual objects perceived. However, when touch and
      vision are combined, vision normally dominates--a phenomenon known as visual
      capture. Here we report a cross-modal interaction between active touch and
      vision: The perceived number of brief visual events (flashes) is affected by the
      number of concurrently performed finger movements (keypresses). This sensorimotor
      illusion occurred despite little ambiguity in the visual stimuli themselves and
      depended on a close temporal proximity between movement execution and vision.

PMID- 16893000
TI  - Filling a gap in the semantic gradient: color associates and response set effects
      in the Stroop task.
AB  - In the Stroop task, incongruent color associates (e.g., LAKE) interfere more with
      color identification than neutral words do (e.g., SEAT). However, color
      associates have historically been related to colors in the response set. Response
      set membership is an important factor in Stroop interference, because color words
      in the response set interfere more than color words not in the response set. It
      has not been established whether response set membership plays a role in the
      ability of a color associate to interfere with color identification. This issue
      was addressed in two experiments (one using vocal responses and one using manual
      responses) by comparing the magnitude of interference caused by color associates
      related to colors in the response set with that of interference caused by color
      associates unrelated to colors in the response set. The results of both
      experiments show that color associates unrelated to colors in the response set
      interfered with color identification more than neutral words did. However, the
      amount of interference was less than that from color associates that were related
      to colors in the response set. In addition, this pattern was consistent across
      response modalities. These results are discussed with respect to various
      theoretical accounts of Stroop interference.

PMID- 16893001
TI  - The context-specific proportion congruent Stroop effect: location as a contextual
      cue.
AB  - The Stroop effect has been shown to depend on the relative proportion of
      congruent and incongruent trials. This effect is commonly attributed to
      experiment-wide word-reading strategies that change as a function of proportion
      congruent. Recently, Jacoby, Lindsay, and Hessels (2003) reported an item
      specific proportion congruent effect that cannot be due to these strategies and
      instead may reflect rapid, stimulus driven control over word-reading processes.
      However, an item-specific proportion congruent effect may also reflect learned
      associations between color word identities and responses. In two experiments, we
      demonstrate a context-specific proportion congruent effect that cannot be
      explained by such word-response associations. Our results suggest that processes
      other than learning of word-response associations can produce contextual control
      over Stroop interference.

PMID- 16893003
TI  - Stimulus- and response-conflict-induced cognitive control in the flanker task.
AB  - Recently, several studies have been conducted to investigate the top-down
      adjustments made after incongruent trials during conflict tasks. In the present
      study, we investigated conflict monitoring with different types of conflict. In a
      modified version of the flanker task, a distinction was made between stimulus
      stimulus conflict and stimulus-response conflict. Six colors were mapped to three
      responses in order to exclude all sequences in which a relevant or an irrelevant
      stimulus- or response-related feature was repeated from trial n-1 to trial n. An
      analysis of the effect of the congruency of the previous trial demonstrated that
      conflict adaptation was present. The stimulus congruency effect was reduced after
      both a stimulus-incongruent trial and a response-incongruent trial. The response
      congruency effect did not vary as a function of previous congruency. These
      findings are discussed in relation to the distinction between conflict detection
      and conflict regulation.

PMID- 16893002
TI  - Relevant distractors do not cause negative priming.
AB  - Highly relevant stimuli (such as one's own name) can capture attention in
      situations in which one can only partially attend to the environment (e.g., the
      classic "cocktail party" phenomenon, introduced by Moray, 1959). The present
      study extends previous findings on selection tasks demonstrating these intrusions
      of relevant stimuli. Not only can highly relevant stimuli be detected more
      easily, but attempts to deliberately ignore them will also be hampered, so
      subsequent reactions to such stimuli will not be slowed. In the experiment,
      participants (N = 32) ignored the first names of other participants without
      problems, and they showed slowed reactions to such names that they had ignored
      shortly before (negative priming task). In contrast, no slowing was observed for
      participants' own names when those names had just previously been used as
      distractors.

PMID- 16893005
TI  - Associated or dissociated effects of syllable frequency in lexical decision and
      naming.
AB  - Most empirical work investigating the role of syllable frequency in visual word
      recognition has focused on the Spanish language, in which syllable frequency
      seems to produce a classic dissociation: inhibition in lexical decision tasks but
      facilitation in naming. In the present study, two experiments were run in German,
      using identical stimulus materials, in a lexical decision task and a naming task.
      In both tasks, there was an inhibitory effect for words with a high-frequency
      first syllable. This pattern of results, suggesting a stronger weight of lexical
      access in the naming process in German than in Spanish, is discussed with regard
      to the issue of stress assignment in the two languages and within the framework
      of word production models. Items, mean response latencies, and accuracy rates per
      item for both experiments can be downloaded from www.psychonomic.org/archive.

PMID- 16893004
TI  - Preparatory adjustment of cognitive control in the task switching paradigm.
AB  - In this article, the authors investigate the assumption that preparation while
      switching between cognitive tasks is dynamically adjusted to the current task
      demands. Performance in high-shift blocks (75% shifts) was compared with
      performance in high-repetition blocks (75% repetitions). This probability
      information was given either at the beginning of a block (global condition) or by
      specific probability cues before every trial (local condition). The authors
      report strong preparation effects (activation of the probable task and inhibition
      of the improbable task) in high-shift blocks, especially when specific
      probability cues were provided. In high-repetition blocks, however, the
      preparation effects were less pronounced. The results support the assumption that
      preparation is dynamically adjusted to the expected task requirements.

PMID- 16893006
TI  - Orthographic complexity and word naming in Italian: some words are more
      transparent than others.
AB  - Italian is a language with a transparent orthography in which printed words can
      be translated into the correct sequence of phonemes using a limited set of rules.
      The rules of letter-sound conversion are, however, simpler for some letters than
      for others: The pronunciations of sequences involving the letters c and g are
      determined by complex (i.e., context-sensitive) rules that depend on the letters
      that follow them. In this article, we report two experiments in which Italian
      participants read aloud words containing simple or complex letter-sound
      conversion rules. In Experiment 1, we found that words containing complex rules
      were read more slowly than words containing simple, noncontextual rules. In
      Experiment 2, we found that the effect of rule complexity on naming speed held
      for low-frequency words but not high-frequency words. The results are interpreted
      in terms of a dual-route model in which rule complexity effects arise from
      sublexical procedures that are more involved in reading low-frequency words than
      high-frequency words. The experimental material used in this study may be
      downloaded from www.psychonomic.org/archive.

PMID- 16893008
TI  - Preventing and treating nicotine addiction: a review with emphasis on adolescent
      health.
AB  - This article is the fourth in a series of four providing current, state-of-the
      art information about the tobacco problem and how physicians can effectively
      intervene. The articles review the health effects of second-hand smoke, current
      treatment strategies for nicotine addiction and the implementation of best
      practices, such as the "5 As," to effectively intervene with families with
      smokers. Three of the articles are accredited for free continuing medical
      education (CME) credit for physicians. To obtain AMA PRA Category 1 Credit(s)TM
      for this article, please go online to www.PedsEducation.org, your source for free
      continuing medical education from Nemours. Choose "Online Education" and the
      article, and complete the post-test as directed. CME accreditation for this
      educational presentation is provided at no cost as a service of Nemours, one of
      the nation's largest children's health systems. Nemours is accredited by the
      Accreditation Council for Continuing Medical Education to provide continuing
      medical education for physicians. Nemours designates this educational activity
      for a maximum of .5 AMA PRA Category 1 Credit(s). Physicians should only claim
      credit commensurate with the extent of their participation in the activity. This
      article will focus on the prevention of adolescent smoking and discuss a global
      approach to the tobacco problem among youth. It also reviews the rationale for
      and pharmacology of treating nicotine addiction to empower physicians to assist
      smokers with quitting. By reading the article and completing the post-test, it is
      anticipated that the following learning objectives will be met: Physicians will
      become familiar with: 1) Options for treating nicotine addiction, 2) The unique
      aspects of the tobacco problem in adolescence, 3) The risk factors for teen
      smoking initiation.

PMID- 16893007
TI  - Proverb preferences across cultures: dialecticality or poeticality?
AB  - Peng and Nisbett (1999) claimed that members of Asian cultures show a greater
      preference than Euro-Americans for proverbs expressing paradox (so-called
      dialectical proverbs; e.g., Too humble is half proud). The present research
      sought to replicate this claim with the same set of stimuli used in Peng and
      Nisbett's Experiment 2 and a new set of dialectical and nondialectical proverbs
      that were screened to be comparably pleasing in phrasing. Whereas the proverbs
      were rated as more familiar and (in Set 1) more poetic by Chinese than by
      American participants, no group differences were found in relation to proverb
      dialecticality. Both the Chinese and Americans in our study rated the dialectical
      proverbs from Peng and Nisbett's study as more likable, higher in wisdom, and
      higher in poeticality than the nondialectical proverbs. For Set 2, both groups
      found the dialectical proverbs to be as likable, wise, and poetic as the
      nondialectical proverbs. When poeticality was covaried out, dialectical proverbs
      were liked better than nondialectical proverbs across both stimulus sets by the
      Chinese and the Americans alike, and when wisdom was covaried out, the effect of
      dialecticality was reduced in both sets and groups. Our findings indicate that
      caution should be taken in ascribing differences in proverb preferences solely to
      cultural differences in reasoning.

PMID- 16893009
TI  - Groundbreaking Delaware physicians: Doctor Margaret Irving Handy.

PMID- 16893010
TI  - Take the reins in mounting your malpractice defense.

PMID- 16893011
TI  - The recent opinion regarding musculoskeletal pain and opiates.

PMID- 16893012
TI  - [Encephalitis and encephalopathy: progress in their diagnosis and treatment].

PMID- 16893013
TI  - [Viral meningitis and encephalitis].

PMID- 16893014
TI  - [Herpes encephalitis].

PMID- 16893015
TI  - [Bacterial meningitis, brain abscess and subdural empyema].

PMID- 16893016
TI  - [Tuberculous meningoencephalitis].

PMID- 16893017
TI  - [Parasitic myelitis].

PMID- 16893019
TI  - [Influenza encephalopathy and Reye's syndrome].

PMID- 16893018
TI  - [Toxoplasma encephalitis].

PMID- 16893020
TI  - [Limbic encephalitis].

PMID- 16893021
TI  - [Progressive multifocal leukoencephalopathy].

PMID- 16893022
TI  - [Prion disease].

PMID- 16893023
TI  - [Encephalitis and encephalopathy associated with AIDS].

PMID- 16893024
TI  - [Encephalopathies caused by antineoplastic agents].

PMID- 16893025
TI  - [Reversible posterior leukoencephalopathy syndrome (RPLS)].

PMID- 16893026
TI  - [Encephalopathy of unknown etiology with suspected involvement of Pleurocybella
      porrigens (Pers.:Fr.) Sing.1. Incidence in Japan].

PMID- 16893027
TI  - [Encephalopathy of unknown etiology with suspected involvement of Pleurocybella
      porrigens (Pers.:Fr.) Sing. 2. Pleurocybella porrigens-encephalopathy clustering
      among patients with kidney failure].

PMID- 16893028
TI  - [Encephalopathy of unknown etiology with suspected involvement of Pleurocybella
      porrigens. 3. From the viewpoint of neurological internal medicine--compilation
      of cases from Akita Prefecture].

PMID- 16893029
TI  - [Encephalopathy of unknown etiology with suspected involvement of Pleurocybella
      porrigens. 4. From the viewpoint of brain imaging and neuropathology].

PMID- 16893030
TI  - [Encephalitis and encephalopathy of unknown etiology: discussion].

PMID- 16893031
TI  - [Alcoholic ketoacidosis with severe abdominal pain].

PMID- 16893032
TI  - [Cibenzoline succinate induced pneumonitis].

PMID- 16893033
TI  - [Overwhelming postsplenectomy infection complicated with disseminated
      intravascular coagulation and acute renal failure].

PMID- 16893034
TI  - [Two cases of intrapulmonary tuberculomas developed during treatment for
      tuberculous pleural effusion].

PMID- 16893035
TI  - [Hypoglycemia associated with hyperinsulinemia in a subject with type 2 diabetes
      and liver cirrhosis].

PMID- 16893036
TI  - [Molecular targeting therapy of hematopoietic tumors].

PMID- 16893037
TI  - [Detection of autoantibody against cancer antigen and its clinical application].

PMID- 16893038
TI  - [Medical accidents involving diagnostic and therapeutic use of endoscopy of the
      digestive system and measures to be taken for safety (data from the Ministry of
      Health, Labor and Welfare)].

PMID- 16893041
TI  - Intraoperative suture use.

PMID- 16893042
TI  - Music for pain relief.

PMID- 16893043
TI  - Looking back, looking forward. A personal journey.

PMID- 16893044
TI  - Conflict resolution training in the NHS.
AB  - The following article is based on a presentation at AfPP's Annual Congress in
      October 2005. It deals with the increasing level of violence and aggression
      directed towards NHS staff in the workplace and advises on conflict resolution.

PMID- 16893045
TI  - A new vision for day surgery.
AB  - The premise that underlines this article (based on a presentation delivered at
      AfPP's Annual Congress in October 2006) is that all elective surgery performed in
      this country should be day surgery. This should eventually include patients
      undergoing hip replacements, radical prostatectomies, aortic aneurysm repair and
      hepatectomies, to name a few. All of these procedures we should perform, safely
      and well, under the British definition of day surgery as 'going home at the end
      of the day'.

PMID- 16893046
TI  - Effects of chlorine solutions on footwear.
AB  - Operating theatre personnel need to disinfect floors, other surfaces and
      sometimes their footwear with chlorine solutions in order to comply with
      Department of Health (DH) guidance on the safe method of dealing with blood
      spills. This study was designed to determine the effect of repeated applications
      of chlorine solutions to a new theatre clog manufactured from high density
      polyurethane.

PMID- 16893047
TI  - Should it happen to you...

PMID- 16893048
TI  - Arbuthnot Lane.
AB  - As part of his series of articles exploring the lives of those behind great
      surgical innovations, Professor Harold Ellis looks at the work of Sir William
      Arbuthnot Lane, who was responsible for pioneering many surgical techniques.

PMID- 16893049
TI  - Magnetic resonance imaging systems: evaluation of 1.5-Tesla systems.
AB  - Magnetic resonance imaging (MRI) systems manipulate magnetic fields and radio
      frequency signals to create diagnostic images of human anatomy. An MR system is
      an essential clinical tool, but the cost of buying and installing one is high, so
      it's crucial that hospitals choose a model carefully. The selection process is
      made more complex by the numerous options available: different field strengths,
      gradient systems, coils, and channels, to name just a few. Also, some systems are
      better than others at facilitating specialized imaging, such as breast and
      cardiac studies. Our Evaluation is intended to help clarify the choices. We
      tested three 1.5-tesla systems from three suppliers--GE, Siemens, and Toshiba. We
      rate the systems for two different uses: inpatient imaging (performed in
      hospitals) and outpatient imaging (most often performed in imaging centers). For
      inpatient facilities, which are likely to have less responsive patients and to
      treat more complex medical problems, the most important purchase considerations
      will be patient positioning features, advanced imaging capabilities, and system
      integration. For outpatient facilities, the ability to perform routine exams
      efficiently and comfortably will be most important. We also provide separate
      ratings for each system's ability to meet the needs of three specialized
      applications--breast imaging, cardiac imaging, and functional MRI.

PMID- 16893050
TI  - Hazard report. Foldable wheelchairs injure patients' fingers.

PMID- 16893051
TI  - [Superoxide dismutase in plant cells].
AB  - Superoxide dismutase (SOD) is one of the key components of defense system, which
      protect cells and tissues from oxidative destruction. The unique nature of this
      enzyme among other antioxidants, its localization in different intracellular
      compartment are reviewed in addition to enzyme behaviour under unflavourable
      influences. Besides, we considered questions of regulation of SOD activity,
      participation of such intracellular macromolecules as reactive oxygen species,
      calcium iones, phytogormones, and nitric oxide in this regulation, as well as
      phosphoralation/dephosphorylation process.

PMID- 16893053
TI  - [Ultrastructural changes in the MP3 neuron of the mollusk Lymnaea stagnalis after
      cryopreservation of the isolated brain].
AB  - Investigation of a possibility of long-term storage of frozen (-196 degrees C)
      viable neurons and nervous tissue is one of the central present day problems. In
      this study ultrastructural changes in neurons of frozen-thawed snail brain were
      examined as a function of time. We studied the influence of cryopreservation,
      cryoprotectant (Me2SO), cooling to 4-6 degrees C, and a prolonged incubation in
      physiological solution at 4-6 degrees C on dictyosomes of Golgi apparatus,
      endoplasmic reticulum (ER) cisternae and mitochondria. It has been found that
      responses of these intracellular structures of cryopreserved neurons to the above
      influences are similar: dissociation of Golgi dictyosomes, swelling of
      endoplasmic reticulum cisternae and mitochondrial cristae. Both freezing-thawing
      and cryoprotectant were seen to cause an increase in the number of lysosomes,
      liposomes, myelin-like structures, and to form large vacuoles. The structural
      changes in molluscan neurons caused by cryopreservation with Me2SO (2 M) were
      reversible.

PMID- 16893052
TI  - [Mitotic index of meristematic cells and root growth of Pisum sativum is affected
      by inositol cycle modulators].
AB  - Relationships between cell division and inositol cycle modulation caused by
      different effectors in roots of Pisum sativum were studied. Stimulation of the
      inositol cycle by myoinositol increased the mitotic index of meristematic cells
      and root length, while the inhibition of the cycle with Li+ and a heavy metal
      Gd3+ considerably decreased mitotic activity and growth. Exposure of roots to 10
      mM CaCl2 and 15 mM myoinositol resulted in the accumulation of chromosome
      aberrations. Changes in the activity of inositol cycle are assumed to be involved
      in the root growth control.

PMID- 16893054
TI  - [Diagnosticum of abnormalities of plant meiotic division].
AB  - Abnormalities of plant meiotic division leading to abnormal meiotic products are
      summarized schematically in the paper. Causes of formation of monads, abnormal
      diads, triads, pentads, polyads, etc. have been observed in meiosis with both
      successive and simultaneous cytokinesis.

PMID- 16893055
TI  - [Plant resistance inductors and active forms of oxygen. III. The influence of
      bisol 2 and baitan on morphogenesis and defense response of wheat non-morphogenic
      callus cells infected with smut agent].
AB  - A study was made of the influence of bisol 2 and baitan compounds on
      morphogenesis and defence response of wheat calluse cells infected with bunt
      agent in associated with oxalate oxidase activation. After introduction of bisol
      and baitan into cultivation medium, dense area with meristema zones, germs of
      shoots and rhizoids appeared on non-morphogenic calluses, which correlated with
      enzyme activation. Parenchyma-like cells, generating hydrogen peroxide, were seen
      in the site of pathogen penetration under infestation, but were never revealed in
      control. Generation of hydrogen peroxide in the site of infection was accompanied
      with an increased oxalate oxidase activity in the cytoplasmic fraction, and with
      suppression of this activity in a fraction bound to the cell wall. Both compounds
      induced oxalate oxidase activity under combined cultivation of wheat calluses
      with bunt agent.

PMID- 16893057
TI  - [Neurogliaform cells: neurochemistry, spatial arrangement, and their role in the
      neocortical inhibitory system].
AB  - The neurogliaform cells (NGFC) localized in area 4 of the human motor cortex were
      found to express choline acetyl transferase (ChAT), GABA, and calbindin. ChAT
      positive neurons were located in cortical layer II. Their dendrites lay in a
      close proximity to those of pyramid cells, neighbouring neurogliaform cells, and
      bodies and dendrites of other cortical neurons. The NGFCs revealed by Golgi
      staining fell into two groups. Cells of the first group had locally (within
      cortical layer II) spreading axons, while those of the second group had axons
      extending into the adjacent layers. Neurochemical heterogeneity of NGFCs is
      discussed in the context of information processing in cortical modules and
      interaction of excitatory and inhibitory interneurons.

PMID- 16893056
TI  - [Oxidized glutathione induces activation of the epidermal growth factor receptor
      and MAP kinases ERK 1,2].
AB  - Ligand-independent activation ("transactivation") of the epidermal growth factor
      receptor (EGFR) was demonstrated upon cell stimulation with cytokines, activators
      of G-protein-coupled receptors and various stressors. Recently, we showed
      transactivation of EGFR and activation of transcription factor STAT3, rather than
      STAT1, induced by glutathione disulfide (GSSG) and glutoxim in epidermoid
      carcinoma A431 cells (Burova et al., Dokl. Akad. Nauk., 2005, 404: 1-3). Glutoxim
      (PHARMA-VAM, Moscow) is a pharmacological synthetic analogue of GSSG, whose
      therapeutic use as an immunomodulator has been permitted. In this study, we
      investigated dynamics of EGFR activation upon A431 cell stimulation with GSSG and
      glutoxim. The time course of activation has a sinuous pattern. It has been shown
      that the intrinsic EGFR tyrosine kinase is responsible for the receptor
      phosphorylation induced by GSSG and glutoxim. Here, we also demonstrated the
      activation of ERK 1,2 upon treatment of A431 cells and HER14 cells (HIN 3T3
      fibroblasts transfected with full-length EGFR) with these drugs. ERK 1,2
      activation was abolished by AG1478, a pharmacological inhibitor of EGFR tyrosine
      kinase, implicating intrinsic EGFR tyrosine kinase in this process.

PMID- 16893058
TI  - [Dynamics of rat hepatocyte histone glycoxidation after general x-ray
      irradiation].
AB  - Dynamics of structural parameters of hepatocyte histone glucoxidative
      modification 3, 9 and 24 h after general X-ray irradiation of rats at dose 5 Gy
      was studied. Dynamics of these parameters (content of carbonyl groups, bityrosyl
      cross-linkings, pentosidines, advanced glycation end products) was compared with
      alterations in DNA structure (according to agarose gel electrophoresis) and lipid
      peroxidation extent (by malondialdehyde content). Oxidative stress induced by
      hepatocyte irradiation results in structural damage of DNA and histones
      accompanied by an increase of histone bityrosyl cross-linking and carbonyl
      content. The content of advanced glycation end products in histones corresponds
      to the extent to DNA damage and malondialdehyde content. The described
      postradiation modifications of histones may be important for regulation of
      chromatin function.

PMID- 16893059
TI  - [Transgenerational transmission of bovine satellite DNA in transgenic mice].
AB  - Genetical, cytogenetical and molecular analysis was made for 5 generations of
      mice transgenic for bovine satellite DNA (Sat). In all cases transgenic mice were
      generated by crosses of transgenic males and females with normal (CBA x C57B1)
      mice. No abnormalities in the founder development were noticed. A normal (near 50
      %) ratio of transgenic and nontransgenic offsprings was observed in blastocysts.
      However, profound differences occurred in the rate of transgene bearing
      offsprings, depending on the sex of grandparents rather than of parents. The
      grandfather Sat transmission resulted in the appearance of 0-52.4 % transgenic
      grandchildren, whereas the grandmother transmission ended in the theoretically
      expected rate. This means that stabilization of transsatellite took place upon
      the female germ line transmission (a positive grandmother effect). It is
      essential that in hemizygous transsatellite mice Sat integration led to the
      occurrence of mammary tumors, inflammation of uterine horns, and infringement of
      mother care of transgenic females. Simultaneous FISH and G-banding showed Sat to
      be localized in the internal region of chromosome 12 near Pax 9 and Brms 11
      genes. Commonly, these genes are implicated in tumorigenesis as their expression
      decreases. Thus, a kind of silencing effect of these genes' expression may be
      supposed.

PMID- 16893060
TI  - [Heat shock proteins of freshwater protists and their involvement in adaptation
      to changes in the environmental salinity].
AB  - Changes in the level of heat shock proteins (HSP) in cells of freshwater
      protists, amoebae Amoeba proteus and ciliates Paramecium jenningsi, in response
      to changes in the environmental salinity were investigated. Changes in salinity
      levels were considered as a stress factor. The immunoblotting method revealed a
      polypeptide antigen cross-reacting with antibodies against bovine HSP70 in total
      protein extracts of both intact cells and cells subjected to salinity stress. The
      same polypeptide antigen was revealed in A. proteus cells subjected to heat
      shock. Therefore, it may be supposed that the polypeptide revealed after salinity
      shock is a heat shock protein related to the vertebrate HSP70. Under the impact
      of stress factor, well acclimated protists mostly spend their own previously
      accumulated HSP70. A conclusion is made that freshwater protists, living under
      conditions of increased salinity, appear to be preadapted to changes in
      environmental factors.

PMID- 16893061
TI  - Cross-disciplinary research stirs new challenges into the study of the structure,
      function and systems biology of complement.

PMID- 16893062
TI  - Liver regeneration: a link to inflammation through complement.

PMID- 16893063
TI  - The role of third complement component (C3) in homing of hematopoietic
      stem/progenitor cells into bone marrow.

PMID- 16893064
TI  - Complement system and the eye.

PMID- 16893065
TI  - To regeneration...with complement.

PMID- 16893066
TI  - Self, non-self, and danger: a complementary view.
AB  - Complement is a sophisticated system of molecules that is critical to the
      functional integrity of the body. Initially considered as a defense system to
      ward off infections, it becomes increasingly clear that the complement system is
      one of the most important humoral systems to sense danger, i.e., to recognize
      conserved patterns on pathogens and on altered/damaged self. In addition to this
      important role in danger recognition, the complement system has the ability to
      translate the danger information into an adequate cellular innate or adaptive
      immune response. This is accomplished by two distinct mechanisms: (a) danger
      sensors that have recognized altered cells or pathogens can directly activate
      cell-bound receptors (e.g., C1q/C1q receptor interaction), and/or (b) danger
      sensors initiate cleavage of complement factors C3 and C5, the fragments of which
      acquire the ability to bind to complement receptors and/or regulators. It is the
      specific interaction of the danger sensors and of the cleavage fragments with
      distinct cell-bound receptors/regulators that directs the immune response toward
      an innate or an adaptive phenotype. Further, the expression pattern of the
      complement receptors critically impacts the shape of the immune response.
      Complement has the ability to discriminate between physiological and pathological
      danger, i.e., physiological cell death and death in response to injury. In the
      former case, cells are merely flagged for enhanced phagocytosis (by C3 fragments)
      without accompanying inflammation (through CR3), whereas in the latter case
      inflammatory signals are accessorily triggered (e.g., by the release of ATs,
      which recruit and activate neutrophils, eosinophils, etc.). This function is of
      major importance for apoptotic cell clearance and tissue repair but plays also
      important roles in fibrotic tissue remodeling in response to chronic tissue
      injury. Further, complement cleavage fragments may prevent the development of
      maldaptive immune responses at the mucosal surface. Here, complement fragment C5a
      does not act as a danger transmitter but as a "homeostasis transmitter," as its
      interaction with the C5a receptor on DCs provides a signal that prevents DCs from
      activating CD4+ T cells. The generation of regulatory T cells in response to CD46
      ligation may have a similar function, as injured cells lose CD46 expresssion,
      which may lead to decreased proliferation of Tregs and, consecutively, increased
      production of T effector cells. Although we are still at the beginning of
      understanding the complex interaction patterns within the complement system,
      recent data suggest substantial crosstalk between the signaling pathways
      downstream of complement receptors and other receptors of the innate immune
      system that function as immune sensors and/or transmitters (i.e., TLRs,
      FcgammaRs130,131). Given the importance of complement as a sensor and effector
      system of innate and adaptive immune responses, a complement-related view of the
      immune system might help to unravel some enigmas of autoimmunity, allergy, and
      transplantation.

PMID- 16893067
TI  - gC1qR/p33 serves as a molecular bridge between the complement and contact
      activation systems and is an important catalyst in inflammation.
AB  - The receptor for the globular heads of C1q, gC1qR/p33, is a ubiquitously
      expressed protein, which is distributed both intracellularly and on the cell
      surface protein. In addition to C1q, this molecule also is able to bind several
      other biologically important plasma ligands, including high-molecular-weight
      kininogen (HK), factor XII (FXII), and multimeric vitronectin. Previous studies
      have shown that incubation of FXII, prekallikrein, and HK with gC1qR leads to a
      zinc-dependent and FXII-dependent conversion of prekallikrein to kallikrein, a
      requisite for kinin generation. In addition, these studies showed that normal
      plasma, but not plasma deficient in FXII, PK, or HK, activate upon binding to
      endothelial cells (EC), and that this activation could be inhibited by antibody
      to gClqR. In these studies, we show that incubation of serum with microtiter
      plate bound gC1qR results in complement activation, as evidenced by the binding
      and activation of C1 and generation of C4d. However, neither Clq-deficient serum
      nor a truncated form of gC1qR (gC1qRA74-96), supported complement activation.
      Taken together, the data strongly suggest that at sites of inflammation, such as
      vasculitis and atherosclerosis, where gC1qR as well as its two important plasma
      ligands, C1q and HK, have been shown to be simultaneously present, soluble or
      cell-surface-expressed gC1qR may contribute to the inflammatory process by
      modulating complement activation, kinin generation, and perhaps even initiation
      of clotting via the contact system. Based on these and other published data, we
      propose a model of inflammation in which atherogenic factors (e.g., immune
      complexes, virus, or bacteria) are perceived not only to convert the endothelium
      into a procoagulant and proinflammatory surface, but also to induce enhanced
      expression of cell surface molecules such as gC1qR. Enhanced expression of gC1qR
      in turn leads to: (i) high-affinity C1q binding and cell production of
      proinflammatory factors, and (ii) high-affinity HK binding and facilitation of
      the assembly of contact activation proteins leading to generation of bradykinin
      and possibly coagulation through activation of FXI.

PMID- 16893069
TI  - Diversified components of the bony fish complement system: more genes for
      robuster innate defense?

PMID- 16893068
TI  - Possible immunoprotective and angiogenesis-promoting roles for malignant cell
      derived prostasomes: a new paradigm for prostatic cancer?

PMID- 16893070
TI  - C5b-9 complement complex in autoimmune demyelination: dual role in
      neuroinflammation and neuroprotection.

PMID- 16893071
TI  - The double-edged flower: roles of complement protein C1q in neurodegenerative
      diseases.
AB  - A role for the complement cascade in AD neuropathology was hypothesized over a
      decade ago, and the results of a significant number of in vitro studies are
      consistent with the involvement of this pathway in AD pathogenesis (reviewed in).
      Since C1q is colocalized with thioflavine-positive plaques and the C5b-9
      complement membrane attack complex is detected in AD brain at autopsy, it is
      reasonable to hypothesize that complement activation has a role in the
      manifestation of AD either by its lytic capacity or as a trigger of glial
      infiltration and initiation of potentially damaging inflammation. The observed
      diminished glial activation and reduced loss of neuronal integrity in a murine
      model overexpressing mutant human APP but lacking the ability to activate the
      classical complement cascade provide the first direct evidence for a detrimental
      role of C1q, and presumably activation of the classical complement pathway in an
      animal model of AD. Research is now focused on generating mouse models that more
      closely mimic the human disease, so that the role of complement activation and
      inflammation on the behavioral/learning and memory dysfunction that occurs in
      this disease can be assessed. In addition, candidate therapies such as targeted
      inhibition of complement activation will need to be tested in these animal models
      as a step toward treatment of humans with the disease. However, it is important
      that the potential for a protective effect of C1q early on in disease progression
      should not be overlooked. Rather, strategies that enhance or mimic the protective
      effects of C1q as well as strategies that inhibit the detrimental processes
      should be fully investigated.

PMID- 16893072
TI  - The role of the complement system in the pathogenesis of experimental autoimmune
      encephalomyelitis and multiple sclerosis.

PMID- 16893073
TI  - The complement system: a potential target for stroke therapy.

PMID- 16893074
TI  - Observations on complement activity in the two-stage inflammatory/hemostatic
      response in the baboon and human models of E. coli sepsis and endotoxemia.

PMID- 16893075
TI  - Complement activation during sepsis in humans.

PMID- 16893076
TI  - Three distinct profiles of serum complement C4 proteins in pediatric systemic
      lupus erythematosus (SLE) patients: tight associations of complement C4 and C3
      protein levels in SLE but not in healthy subjects.
AB  - The serial changes of serum complement proteins C4 and C3 in SLE were
      characterized in 33 pediatric SLE patients with defined C4 genotypes. Three
      distinct groups of C4 protein profiles were observed. The first group was
      characterized by persistently low C4 levels (<10 mg/dL) throughout the course of
      the study. Patients with this profile had mild disease manifestations and low to
      medium copy numbers of C4 genes. The second group featured periodic fluctuations
      of serum C4 protein concentrations above and below 10 mg/dL, paralleled with ups
      and downs of SLE disease activities. Most patients with the second profile had
      unequal copy numbers of C4A and C4B genes and relatively severe disease. The
      third group had normal serum C4 levels (>15 mg/dL) most of the time and
      occasionally low C4 and C3 levels that were mostly coincident with disease flares
      prior to effective medical treatment. Most patients in this group

PMID- 16893077
TI  - A minimum CR2 binding domain of C3d enhances immunity following vaccination.
AB  - The degradation product of the third (C3) complement component, C3d, links innate
      and adaptive immunity, and the covalent attachment of C3d to an antigen enhances
      antigen-specific immune responses. C3d has been hypothesized to enhance immunity
      by direct interaction with complement receptor 2 (CR2/CD21) on immune cells.
      However, the domains on C3d important for CR2 binding have been controversial,
      with various studies reaching contradictory conclusions. In addition, the concept
      of B-cell activation via CR2 by C3d has been questioned, since mice lacking CR2
      still elicit C3d-enhanced immunity following vaccination. Therefore, the goal of
      this study was to determine if a peptide representing one of the proposed CR2
      binding domains of C3d could substitute for the entire protein and enhance
      antigen-specific immunity. Mice (BALB/c) were vaccinated with the HIV-1 gp120
      envelope glycoprotein (Env(gp120)) alone or fused to multiple copies of the
      murine C3d or a twenty-eight amino-acid peptide (P28) containing a minimum CR2
      binding domain. Each immunogen was expressed from DNA plasmid in vivo or injected
      as purified recombinant protein. The fusion of the P28 peptide to Env(gp120)
      enhanced both humoral and cell-mediated immune responses with similar efficiency
      as Env(gp120) conjugated to C3d. The fusion of C3d or P28 to Env(gp120) elicited
      higher-titer anti-Env specific antibody, enhanced avidity maturation of the
      elicited antibody, and elicited higher numbers of IFN-gamma and IL-4 secreting
      cells compared to Env(gp120) immunizations. This CR2-binding domain specific 28
      amino acid peptide can substitute for the entire C3d molecule and enhance
      immunity. These results indicate that the adjuvant properties of C3d are
      associated with CR2 interaction.

PMID- 16893078
TI  - Structure and function of ficolins.

PMID- 16893079
TI  - Role of mannose-binding lectin (MBL2) genotyping in predicting the risk of
      recurrent otitis media (rOM).

PMID- 16893080
TI  - Conformational complexity of complement component C3.

PMID- 16893081
TI  - Disease-associated sequence variations in factor H: a structural biology
      approach.

PMID- 16893082
TI  - Transdermal pharmacology of small molecule cyclic C5a antagonists.
AB  - Overproduction or underregulation of the proinflammatory complement component C5a
      has been implicated in numerous immune and inflammatory conditions. Therefore,
      targeting the C5a receptor (C5aR) has become an innovative strategy for
      antiinflammatory drug development. The novel cyclic peptide C5aR antagonist, AcF
      [OP(D-Cha)WR] (PMX53), attenuates injury in numerous animal models of
      inflammation following intravenous, subcutaneous, intraperitoneal, and oral
      administration. In the present study the transdermal pharmacology of PMX53 and
      three analogs designed with increased lipophilicity, hydrocinnamate-[OP(D
      Cha)WCit] (PMX200), AcF-[OP(D-Cha)WCit] (PMX201) and hydrocinnamate-[OP(D-Cha)WR]
      (PMX205), have been examined in order to assess their transdermal permeability
      and inhibitory effect on C5a-mediated lipopolysaccharide (LPS)-induced systemic
      responses. In the rat, PMX53, PMX201, and PMX205, were bioavailable following
      topical dermal administration (10 mg/50 cm2 site/rat). All analogs functionally
      antagonized neutropenia and hypotension induced by systemic challenge with LPS (1
      mg/kg i.v.). Interestingly, PMX200 attenuated LPS-induced neutropenia more
      effectively than other analogs, despite undetectable (<5 ng/ml) circulating
      levels following topical administration. In conclusion, we have demonstrated that
      cyclic peptide C5aR antagonists can penetrate transdermally sufficiently to have
      systemic effects. However, increasing lipophilicity in these compounds did not
      result in increased blood levels. Nonetheless, topical application of C5aR
      antagonists produced circulating levels of the drugs that antagonized the LPS
      induced systemic responses of neutropenia and hypotension. This suggests that
      these small-molecule C5aR antagonists may be developed for topical administration
      for the treatment of local and systemic inflammatory conditions in the human and
      veterinary pharmaceutical markets.

PMID- 16893083
TI  - Inactivation of complement by recombinant human C3 derivatives.

PMID- 16893084
TI  - Complement analysis in clinic and research.

PMID- 16893086
TI  - Neurocognitive development of visuocognitive motor behavior revealed by event
      related potentials in cued continuous performance test.

PMID- 16893085
TI  - Cell-bound complement activation products (CB-CAPs) as a source of lupus
      biomarkers.
AB  - Measurement of serum C3 and C4 has been used for several decades to monitor
      disease activity in patients with SLE. Despite the limited utility and recognized
      weaknesses of these assays, they have remained the gold standard during an era of
      unprecedented discovery in the complement field. The current urgent need for
      lupus biomarkers warrants efforts to mine the complement system for assays
      superior to serum C3 and C4. Recent studies of soluble and cell-bound complement
      activation products hold promise for achieving this goal.

PMID- 16893087
TI  - Studying higher cerebral functions by transcranial magnetic stimulation.
AB  - TMS can be used to study higher cerebral functions by the virtual lesion
      paradigm. The major advantages of this method are that it could be used to
      produce a lesion anywhere the researcher wants without confusing cortical
      reorganization, and that it helps to establish a chain of cause and effect
      between the activity of the brain and behavior. With elucidation of the mechanism
      underlying the cortical function blocking, this technique will open up new
      possibilities for studying higher cerebral functions. In contrast to the online
      method in which TMS is delivered while subjects perform a certain task, the off
      line method uses repetitive TMS to achieve lasting effects even after stimulation
      has ceased. The application of the offline method will extend from improving
      cognitive functions by TMS to the treatment of neurological and psychiatric
      patients.

PMID- 16893088
TI  - Long-term potentiation (LTP)-like plasticity and learning in human motor cortex-
      investigations with transcranial magnetic stimulation (TMS).

PMID- 16893089
TI  - Cortical activities elicited by viewing mouth movements: a
      magnetoencephalographic study.

PMID- 16893090
TI  - Optimal methods of stimulus presentation and frequency analysis in P300-based
      brain-computer interfaces for patients with severe motor impairment.

PMID- 16893091
TI  - An integrated approach to face and motion perception in humans.

PMID- 16893092
TI  - The role of the basal ganglia and cerebellum in cognitive impairment: a study
      using event-related potentials.

PMID- 16893093
TI  - High-frequency oscillatory activities during selective attention in humans.

PMID- 16893094
TI  - Event-related components of laser evoked potentials (LEPs) in pain stimulation:
      recognition of infrequency, location, and intensity of pain.

PMID- 16893095
TI  - Novelty-related brain response and its clinical applications.

PMID- 16893096
TI  - Cross-modal plasticity in the blind revealed by functional neuroimaging.

PMID- 16893097
TI  - Psychophysics and electrophysiology of human perceptual learning: a summary.

PMID- 16893098
TI  - Two ways of hearing--dissociation between spectral and temporal processes in the
      auditory cortex.

PMID- 16893099
TI  - The mystery of photopsias, visual hallucinations, and distortions.

PMID- 16893100
TI  - Intraoperative neurophysiology of the corticospinal tract of the spinal cord.

PMID- 16893101
TI  - Generators of subcortical components of SEPs and their clinical applications.

PMID- 16893102
TI  - Intraoperative recording of the very fast oscillatory activities evoked by median
      nerve stimulation in the human thalamus.

PMID- 16893103
TI  - Cortical processing of noxious information in humans: a magnetoencephalographic
      study.

PMID- 16893104
TI  - Mechanism of voluntary and involuntary movements in humans.

PMID- 16893105
TI  - High-frequency oscillations in the human motor system.

PMID- 16893106
TI  - Functional changes in cortical components of somatosensory evoked responses by
      stimulus repetition.

PMID- 16893107
TI  - Origins and characteristics of high-frequency (>500 hz) SEP components directly
      recorded from the cervical cord, thalamus, and cerebral cortex.

PMID- 16893108
TI  - The nature of facilitation of motor evoked potentials by heteronymous muscle
      contraction in the lower limb. Interactions between knee and ankle muscles.

PMID- 16893110
TI  - The wavelet transformed EEG: a new method of trial-by-trial evaluation of saccade
      related cortical activity.

PMID- 16893109
TI  - Repetitive transcranial magnetic stimulation (rTMS) in monkeys.

PMID- 16893111
TI  - Functional mapping in epilepsy patients' information from subdural electrodes.

PMID- 16893112
TI  - Are the processes reflected by late and ultra-late laser evoked potentials
      specific of nociception?

PMID- 16893113
TI  - Interaction of somatosensory evoked potentials within the same nerve and between
      the two different nerves: including high-frequency oscillation (HFO).

PMID- 16893114
TI  - Comparison between preoperative and intraoperative localization of cortical
      function in patients with brain tumors.

PMID- 16893115
TI  - Insights into the functional organization of limbic cortical circuits from
      studies of evoked potentials and spontaneous activity.

PMID- 16893116
TI  - Application of dipole models in exploring somatosensory evoked potential sources.

PMID- 16893117
TI  - Hemispheric asymmetry of median nerve somatosensory evoked potentials.

PMID- 16893118
TI  - Electrophysiological assessment of pain.

PMID- 16893119
TI  - Multimodal evoked potentials in patients with pediatric leukodystrophy.

PMID- 16893120
TI  - Partial conduction block in cervical compression myelopathies: waveform changes
      of ascending spinal evoked potentials.

PMID- 16893121
TI  - Immune-mediated potassium channelopathies.

PMID- 16893122
TI  - Abnormal sensorimotor integration in hand dystonia.

PMID- 16893123
TI  - Neurophysiologic studies in Krabbe disease.

PMID- 16893124
TI  - Current understanding of F-wave physiology in the clinical domain.

PMID- 16893125
TI  - What is the evidence justifying non-invasive SEP and MEP monitoring during spinal
      surgery?

PMID- 16893126
TI  - Role of clinical neurophysiology in the diagnosis and management of visual
      disorders.

PMID- 16893127
TI  - Peripheral recovery and central response following toe-to-finger transplantation.

PMID- 16893128
TI  - Some controversies in carpal tunnel syndrome.

PMID- 16893129
TI  - Transcranial magnetic stimulation for upper motor neuron involvement in
      amyotrophic lateral sclerosis (ALS).

PMID- 16893130
TI  - [Autologous bone marrow stem cell or peripheral blood endothelial progenitor cell
      therapy in patients with peripheral limb ischaemia].
AB  - No effective medical therapies have been developed sofar to enhance blood flow in
      the legs of patients with peripheral arterial disease (PAD). For patients with
      limb threatening ischaemia the only option for relief of rest pain or gangraena
      is amputation. There is evidence in experimental and clinical studies that adult
      bone marrow-derived stem cells and endothelial progenitor cells participate in
      the development of new blood vessels, called neoangiogenesis or
      neovascularization. Clinical results induced by autologous bone marrow stem cells
      or angiogenic growth/differentiation factors in end-stage patients with PAD are
      summarized. Considering the relatively few number of patients treated by
      angiogenic therapy, the interpretation of clinical results needs cautiousness.

PMID- 16893131
TI  - [The diagnostics of osteoporosis in the evaluation of fracture risk].
AB  - Osteoporosis is a metabolic bone disease affecting a large portion of the
      population. In the osteoporotic process, organic and inorganic components on the
      bone are reduced, bone quality is deteriorated, strength of bone tissue is
      diminished, thus fracture risk is increasing as a consequence. Knowledge of the
      disease is essential for all physicians due to the frequency of this disorder.
      The aim of osteoporosis diagnostics is to discover the disease, to differentiate
      from other similar disorders, and to estimate fracture risk in order to introduce
      effective treatment. To carry out this task effectively, beside the proper
      evaluation of the patient's history, physical examination, osteodensitometry, X
      ray and laboratory tests, some new factors revealed recently known to influence
      fracture risk should also be considered. The purpose of the present review is to
      summarize most recent data related to the diagnostics of osteoporosis from the
      view of the everyday practice.

PMID- 16893132
TI  - [Genetic background of irritable bowel syndrome].
AB  - Irritable bowel syndrome (IBS) is a functional disorder which affects the 20% of
      the population. The exact origin is unknown. IBS is the result of interaction of
      genes and environmental factors. Familial aggregation and higher concordance rate
      of monozygotic twins compared to dizygotic twins provide evidence for the
      importance of genetic factors in the pathogenesis of IBS. Interest has focused on
      genetic variants of serotonin transporter and receptors, because of their role in
      gut motility, visceral sensitivity, immune processes and mood. Firm conclusions
      about the role of serotonin system, as well as other neuroreceptors, G-proteins,
      cytokine polymorphisms in the pathogenesis of IBS cannot be made.

PMID- 16893133
TI  - [Violence and alcohol consumption in intimate heterosexual relationships].
AB  - Health and addiction harm of violence related to drinking is a very important
      aspect of the recent research studies. The social exchange theory, the family
      systems approach of alcoholism, the psychopharmacological model, the economic
      motivational model, and the tripartitate conceptual framework of Goldstein focus
      on the phenomenon within different causal contexts. According to recent studies
      approximately half of the cases is related to the alcohol consumption. Especially
      the binge drinking can facilitate violence. The problem is moderated by social,
      cultural, and ethnic specialties. The likelihood of alcohol related aggression
      increases in a rapidly changing society. Exposure to drinking related violence is
      frequent among women with pregnancy.

PMID- 16893134
TI  - [A case of hemochromatosis diagnosed in a middle-aged patient with diabetes
      mellitus].
AB  - The authors present the case of a 60-year-old patient admitted for diabetes
      mellitus. Primary (hereditary) hemochromatosis was diagnosed as the pathological
      background of diabetes as well as the associated symptoms (weight loss,
      arthrosis, erectile dysfunction, supraventricular arrhythmia, hepatic cirrhosis).
      To eliminate the accumulated excess iron, phlebotomy cycles were started. Family
      screening revealed two other affected patients who contrary to the index-patient
      were free of complaints. Phlebotomy was, however, started in one of these
      patients because of abnormal laboratory values consistent with iron-overload. For
      the prevention of the symptoms early diagnosis is important. Although some of the
      symptoms can disappear, the most severe changes (cirrhosis, diabetes) are
      irreversible. Latest knowledge about the pathophysiology including the genetic
      background and the practice of diagnosis and treatment of the disease are
      discussed as well.

PMID- 16893135
TI  - [Prevalence of celiac disease in Turner syndrome].
AB  - INTRODUCTION AND AIM: Percentage of coeliac disease among patients with Turner
      syndrome is given differently in a few publication. The aim of the study was to
      assess prevalence of celiac disease in Turner syndrome. PATIENTS AND METHODS:
      Serological screening of coeliac disease were performed in 63 patients with
      Turner syndrome during the last 11.5 years (since 1994). Serological
      investigations were repeated yearly since 2003 in all patients, and the results
      of screening of new patients were completed. Theirs first case of coeliac disease
      was announced in 2004 in Gyermekgyogyaszat (Hun). Further positive serological
      results were found after publication of the first case. RESULTS: Positive results
      were found in seven of 63 patients (two EmA and five antitransglutaminase IgA
      positivity). Intestinal biopsy was applied in all 7 cases. Coeliac disease was
      revealed by histologic analysis in the five cases - 5/63 (7.9%). CONCLUSION: The
      prevalence of coeliac disease in Turner syndrome seems to be higher than in
      general population. This can play role in the insufficient effect of growth
      hormone therapy in the affected patients. The high prevalence indicates that the
      connection between these disorders can not be coincidental. Their cases and the
      available data from the publications indicate that screening of coeliac disease
      in patients with Turner syndrome should be performed and intestinal biopsy is
      recommended in positive cases.

PMID- 16893137
TI  - [Hypertension].

PMID- 16893136
TI  - [Sixteen years of nursing education with diploma at the Semmelweis University].
AB  - Nowadays it is already known that medical sciences on their own cannot achieve
      spectacular improvement in the state of health of the population even with high
      tech appliances. Health care professionals, who can aid individuals, families,
      and communities in optimizing their physical, mental and social functions, are
      also needed in the fields of basic provision and clinical-hospital provision and,
      to achieve this, they possess wider medical, nursing and social scientific
      expertise. The training of registered nurses was first launched in Hungary at the
      Postgraduate Medical Institute's Faculty of Health Care (nowadays Semmelweis
      University Faculty of Health Care) in 1989 as a correspondence, then in 1990 as a
      full-time program. This was the first step towards the realization of a better,
      high-standard, individualized nursing system. The aim is training health care
      professionals who are able to individually assess the needs of people under their
      care, define the problems, plan, execute and evaluate the nursing-caring process,
      and take part in nursing research. Besides the positive results of the follow-up
      examinations of graduate students, the fact cannot be neglected that since the
      introduction of the training, in the last 15 years it has not become clear to
      everyone, why the training of registered nurses is necessary, and what these "new
      type" professionals can be used for. It is clear to everyone that for real
      teamwork the mutual appreciation of each other's work, maximum accord, the
      acceptance and honor of each other are indispensable. Still, all these cannot be
      expected from school qualification only, these can only be achieved with the
      continuous proof of aptitude and expertise. For the realistic judgement of
      registered nurses it is also needed that their nearest colleague, the physician
      should know in depths and accept the syllabus of the training. That is why the
      author of the article feels that the history of the first sixteen years of the
      accredited training is important to be shown, and her message is grouped around
      four most important elements: curriculum, teachers participating in the training,
      practice bases and students.

PMID- 16893138
TI  - Parkinson disease: misunderstood condition.

PMID- 16893139
TI  - Parkinson disease. Changing concepts and treatments.

PMID- 16893140
TI  - Could CMAJ happen at CFP? Report on editorial independence from a former
      scientific editor.

PMID- 16893141
TI  - Integrative medicine. Model for health care reform.

PMID- 16893142
TI  - Rebuttal: are drugs too expensive in Canada?

PMID- 16893144
TI  - A grand seduction indeed.

PMID- 16893143
TI  - Helping expectations become reality for dying cancer patients.

PMID- 16893145
TI  - Gratitude.

PMID- 16893146
TI  - Use of proton pump inhibitors during pregnancy and breastfeeding.
AB  - QUESTION: A 36-year-old pregnant patient has symptoms of peptic disease.
      Treatment with diet and lifestyle modifications and also antacids has given her
      little relief. If she were not pregnant, I would prescribe a proton pump
      inhibitor (PPI) for her. She is now 4 weeks pregnant, and I need to determine
      whether PPIs are safe during pregnancy. ANSWER: Data currently available suggest
      that omeprazole is not teratogenic in humans. While information on other PPIs is
      limited, a systematic review of the evidence suggests that they are also not
      teratogenic.

PMID- 16893147
TI  - Vitamin E for treating children's scars. Does it help reduce scarring?
AB  - QUESTION: A few of my patients have been told to use vitamin E cream after
      surgery or repair of a laceration. What is the evidence for this suggestion, and
      is this treatment suitable for all patients? ANSWER: Vitamin E is the main lipid
      soluble antioxidant in the skin. Several anecdotal reports have suggested that
      topical use of vitamin E cream can reduce scar formation. Current evidence from
      the literature, however, does not support that proposition. In fact, studies
      report some adverse effects with use of vitamin E. Further research is needed
      before application of vitamin E cream becomes the standard of care.

PMID- 16893148
TI  - Is it time for single-inhaler asthma therapy?

PMID- 16893151
TI  - Where have all the residents gone? Part 2: Renewing interest in family medicine.

PMID- 16893150
TI  - Understanding cardiac "echo" reports. Practical guide for referring physicians.
AB  - OBJECTIVE: To help referring physicians extract clinically useful information
      from transthoracic echocardiography (TTE) reports, highlighting current practice
      and innovations that are reflected with increasing frequency in reports issued by
      echocardiac laboratories. QUALITY OF EVIDENCE: Echocardiography is an established
      science. The field has a large body of literature, including peer-reviewed
      articles and textbooks describing the physics, techniques, and clinical
      applications of TTE. MAIN MESSAGE: Transthoracic echocardiography is a basic tool
      for diagnosis and follow-up of heart disease. Items of interest in TTE reports
      can be categorized. In clinical practice, TTE results are best interpreted with a
      view to underlying cardiac physiology and patients' clinical status. Knowing the
      inherent limitations of TTE will help referring physicians to interpret results
      and to avoid misdiagnoses based on false assumptions about the procedure.
      CONCLUSION: A structured approach to reading TTE reports can assist physicians in
      extracting clinically useful information from them, while avoiding common
      pitfalls.

PMID- 16893152
TI  - Working together.

PMID- 16893149
TI  - Approach to diagnosis of Parkinson disease.
AB  - OBJECTIVE: To review the clinical features of Parkinson disease (PD) and other
      causes of motor parkinsonism with an emphasis on diagnosis in elderly patients.
      SOURCES OF INFORMATION MEDLINE: and Google Scholar were searched for original
      research articles describing clinical diagnosis of parkinsonism. Consensus
      statements and articles summarizing diagnostic criteria for parkinsonian
      syndromes were also reviewed. Most evidence was levels II or III. MAIN MESSAGE:
      Diagnosis of PD is made clinically and can be challenging. In older patients, PD
      can present with general functional decline and nonspecific symptoms. Clinical
      criteria for diagnosing PD and the TRAP mnemonic can be helpful. A 2-week trial
      of levodopa-carbidopa treatment can be considered. Specific signs and a minimal
      response to levodopa treatment suggest other causes of parkinsonism. Clinical
      features of other causes of parkinsonism are reviewed in the article. CONCLUSION:
      Parkinsonism and PD are common in older patients. Family physicians should
      consider parkinsonism in the differential diagnosis of patients who have falls
      and exhibit general functional decline.

PMID- 16893153
TI  - Evaluation of small intestinal submucosa grafts for meniscal regeneration in a
      clinically relevant posterior meniscectomy model in dogs.
AB  - Large meniscal defects are a common problem for which treatment options are
      limited. Successful meniscal regeneration has been achieved by using grafts of
      small intestinal submucosa in posterior, vascular meniscal defects in a dog
      model. This study investigates the long-term effects of a tibial tunnel fixation
      technique and a clinically based meniscectomy defect on meniscal regeneration
      using this model. Eight mongrel dogs underwent medial arthrotomy and partial
      meniscectomy. The dogs were divided into groups based on defect treatment: small
      intestinal submucosa (n = 4) or meniscectomy (n = 4). Dogs were scored for
      lameness by subjective scoring postoperatively, sacrificed at 6 months, and
      assessed for articular cartilage damage, gross and histologic appearance of the
      operated meniscus, amount of new tissue in the defect, and relative compressive
      stiffness of articular cartilage. Dogs in the meniscectomy group were
      significantly (P = .002) more lame than dogs treated with small intestinal
      submucosa. Small intestinal submucosa-treated joints had significantly (P = .01)
      less articular cartilage damage than meniscectomy joints. Small intestinal
      submucosa meniscal implants resulted in production of meniscal-like replacement
      tissue, which was consistently superior to meniscectomy in amount, type, and
      integration of new tissue, chondroprotection, and limb function during the study
      period. Small intestinal submucosa implants may be useful for treatment of large
      posterior vascular meniscal defects in humans. The tibial tunnel technique used
      for fixation may have clinical advantages and therefore warrants further
      investigation.

PMID- 16893154
TI  - Clinical outcomes following osteochondral autologous transplantation (OATS).
AB  - This study evaluated the clinical outcome in 21 patients (22 knees) undergoing
      osteochondral autologous transplantation (OATS) in the knee over a 5-year period.
      Sixteen knees in 15 patients were available for follow-up at an average of 40
      months after the procedure. The clinical outcome was analyzed using the IKDC and
      Knee and Osteoarthritis Outcome Score (KOOS) evaluation forms, a subjective
      questionnaire, and a clinical examination. At final follow-up, the average KOOS
      result for pain was 80.6 (range: 56-94), symptoms 53.6 (range: 25-71), function
      of activities of daily living 93.4 (range: 79-100), function of sports and
      recreational activities 65.3 (range: 20-100), and quality of life 51.0 (range: 6
      88). The average IKDC score was 68.2. On our subjective questionnaire, the
      average preoperative grade given was 3.1 (range: 1-7) with an improvement at the
      most recent follow-up to a grade of 8.0 (range: 5-10) (P < .00001). Thirteen
      (86%) patients reported that they would have the surgery again if they had to
      make the decision a second time. Age did not correlate with subjective results on
      the IKDC evaluation (P = .7048) or score difference on our questionnaire (P =
      .9175). This procedure provides an option for articular resurfacing of the
      femoral condyles for focal areas of chondral defects with promising results
      regarding subjective improvement.

PMID- 16893155
TI  - Preoperative computerized radiograph measurement of Blumensaat's line as an aid
      to correct placement of the femoral tunnel in ACL reconstruction.
AB  - Numerous studies have shown that the improper placement of the graft in anterior
      cruciate ligament reconstruction is a major cause of graft failure, capturing of
      the knee, and notch roof impingement. The ideal femoral position is located in
      the posterior one quarter of Blumensaat's line as seen on a true lateral knee
      radiograph. We present a simple method that relies on the use of preoperative
      radiographic measurement and a calibrated guide to ensure that the femoral tunnel
      is sufficiently far back along the roof of the notch, using the easily
      identifiable anterior end of the notch as a reference point.

PMID- 16893156
TI  - Proximity of the popliteal artery to the PCL during simulated knee arthroscopy:
      implications for establishing the posterior trans-septal portal.
AB  - This study defines the sagittal distance from the posterior cruciate ligament
      (PCL) to the popliteal artery under simulated arthroscopic conditions. This
      information is relevant for posterior knee arthroscopy, particularly for the safe
      establishment of the posterior trans-septal portal. Measurements from the PCL to
      the popliteal artery were made on sagittal magnetic resonance images obtained in
      a previous study of 10 fresh-frozen cadaveric knees. The mean sagittal distance
      from the mid-PCL to the popliteal artery was 29.1 +/- 11 mm (range: 18-55 mm).
      The mean sagittal distance from the proximal PCL fovea to the popliteal artery
      was 9.7 +/- 5 mm (range: 3-16 mm). The results of this study provide the
      arthroscopist working in the posterior compartments of the knee with a more
      detailed knowledge of the anatomic relationship between the PCL and popliteal
      artery. This knowledge will help minimize the risk of iatrogenic vascular injury
      during arthroscopic knee surgery.

PMID- 16893157
TI  - Magnetic resonance imaging in the evaluation of tibial eminence fractures in
      adults.
AB  - Proton density and T2-weighted sagittal, axial, coronal, and inversion recovery
      fat suppression magnetic resonance imaging (MRI) sequences were reviewed in 21
      adults (10 men and 11 women) with 22 tibial eminence fractures. Average patient
      age was 43 years (range: 19-62 years). There were 3 type I, 3 type II, 12 type
      III, and 4 type IV fractures. The average fracture fragment size was 21 x 23 mm,
      and the average displacement was 5.5 mm (range: 0-12 mm). The MRI disclosed
      anterior cruciate ligament (ACL) insertional avulsions in 20 (91%), distal
      posterior cruciate ligament (PCL) avulsions in 4 (18%), intrasubstance ACL damage
      in 9 (41%), intrasubstance PCL injury in 3 (14%), medial collateral ligament
      (MCL) tears in 9 (41%) knees, retinacular injury in 8 (36%), posterolateral
      corner damage in 8 (36%), medial meniscal tears in 5 (23%), and 4 (18%) had
      lateral meniscal tears. Occult subchondral osseous injuries were seen in the
      posterolateral tibial plateau in 13 (59%) knees, anterolateral femoral condyle in
      4 (18%), and posteromedial tibial plateau in 5 (23%) knees. Discrete
      osteochondral fractures were present in 7 (32%) knees. Significant osseous,
      cartilaginous, meniscal, and ligamentous damage was discovered in all patients.
      Based on these findings, we recommend MRI evaluation of all tibial eminence
      fractures to accurately detect all knee damage.

PMID- 16893158
TI  - Metabolic mechanisms in the pathogenesis of osteoarthritis. A review.

PMID- 16893159
TI  - The ipsilateral drive through approach to the posterolateral compartment of the
      knee. Surgical technique.

PMID- 16893160
TI  - Late anterior cruciate ligament reconstruction failure by femoral bone plug
      dislodgement. Case report.

PMID- 16893161
TI  - The biology of allograft incorporation.
AB  - Musculoskeletal allografts remain an important, and are sometimes the only,
      treatment option for the reconstruction and replacement of damaged or absent
      musculoskeletal tissues. Understanding the biologic factors that affect the donor
      host interactions and ultimate incorporation and remodeling of various allograft
      tissues is an essential prerequisite for their successful clinical use.

PMID- 16893162
TI  - Soft-tissue allograft processing controversies.

PMID- 16893163
TI  - Allograft meniscus transplantation: background, indications, techniques, and
      outcomes.

PMID- 16893164
TI  - Fresh osteochondral allografts: graft processing and clinical applications.

PMID- 16893166
TI  - The crystal structure of NAD(P)H oxidase from Lactobacillus sanfranciscensis:
      insights into the conversion of O2 into two water molecules by the flavoenzyme.
AB  - The FAD-dependent NAD(P)H oxidase from Lactobacillus sanfrancisensis (L.san-Nox2)
      catalyzes the oxidation of 2 equivalents of either NADH or NADPH and reduces 1
      equivalent of O(2) to yield 2 equivalents of water. During steady-state turnover
      only 0.5% of the reducing equivalents are detected in solution as hydrogen
      peroxide, suggesting that it is not released from the enzyme after the oxidation
      of the first equivalent of NAD(P)H and reaction with O(2). Here we report the
      crystal structure of L.san-Nox2 to 1.8 A resolution. The enzyme crystallizes as a
      dimer with each monomer consisting of a FAD binding domain (residues 1-120), a
      NAD(P)H binding domain (residues 150-250), and a dimerization domain (residues
      325-451). The electron density for the redox-active Cys42 residue located
      adjacent to the si-face FAD is consistent with oxidation to the sulfenic acid
      (Cys-SOH) state. The side chain of Cys42 is also observed in two conformations;
      in one the sulfenic acid is hydrogen bonded to His10 and in the other it hydrogen
      bonds with the FAD O2' atom. Surprisingly, the NAD(P)H binding domains each
      contain an ADP ligand as established by electron density maps and MALDI-TOF
      analysis of the ligands released from heat-denatured enzyme. The ADP ligand
      copurifies with the enzyme, and its presence does not inhibit enzyme activity.
      Consequently, we hypothesize that either NADPH or NADH substrates bind via a long
      channel that extends from the enzyme exterior and terminates at the FAD re-face.
      A homology model of the NADH oxidase from Lactococcus lactis (L.lac-Nox2) was
      also generated using the crystal structure of L.san-Nox2, which reveals several
      important similarities and differences between the two enzymes. HPLC analysis of
      ligands released from denatured L.lac-Nox2 indicates that it does not bind ADP,
      which correlates with the specificity of the enzyme for oxidation of NADH.

PMID- 16893165
TI  - Novel chromophores and buried charges control color in mFruits.
AB  - mFruits are second-generation monomeric red fluorescent proteins (mRFPs) that
      have improved brightness and photostability compared to the first-generation
      mRFP1. The emission and excitation maxima are distributed over the remarkably
      large ranges of about 550-650 and 540-590 nm, respectively; however, the
      variations in the spectra can be traced to a few key amino acids. Spectroscopic
      and atomic resolution crystallographic analyses of three representatives,
      mOrange, mStrawberry, and mCherry, reveal that different mechanisms operate to
      establish the excitation and emission maxima. Evidently, they all undergo the
      second oxidation step to produce an acylimine linkage in the polypeptide
      backbone. In comparison to the progenitor DsRed, direct covalent modification to
      this linkage (mOrange) and indirect modification of the chromophore environment
      (mStrawberry and mCherry) produce strong blue- and red-shifted variants. The blue
      shift of mOrange is induced by an unprecedented covalent modification of the
      protein backbone. The electron-density map indicates the formation of a third
      heterocycle, 2-hydroxy-dihydrooxazole, upon the reaction of Thr 66 Ogamma with
      the polypeptide backbone, which in turn reduces the conjugation of the carbonyl
      at position 65 with the rest of the chromophore. In mStrawberry and mCherry, the
      movement of charged Lys 70 and protonation of Glu 215 are proposed to modify the
      chromophore electron-density distribution, inducing the red shift. pH-dependent
      spectral shifts of mCherry and mStrawberry appear to result from the titration of
      Glu 215, although, for mStrawberry, partial cyclization of Thr 66 may contribute
      at high pH.

PMID- 16893167
TI  - Protonation and hydrogen-bonding state of the distal histidine in the CO complex
      of horseradish peroxidase as studied by ultraviolet resonance Raman spectroscopy.
AB  - Ultraviolet resonance Raman (UVRR) spectroscopy has been used to characterize the
      structure and hydrogen bonding state of the distal histidine (His42) in
      horseradish peroxidase (HRP) complexed with carbon monoxide (HRP-CO). The HRP-CO 
      HRP UVRR difference spectrum in D(2)O solution at pD 7.0 shows two positive
      peaks at 1408 and 1388 cm(-)(1), which are ascribable to medium-to-weak and
      strong hydrogen bonding states, respectively, of the protonated imidazolium side
      chain of His42 in HRP-CO. Both His42 peaks decrease in intensity with increase of
      pD with a midpoint of transition at pD 8.8, indicating that the pK(a) of His42 in
      HRP-CO is 8.8. The CO ligand exhibits two C-O stretching Raman peaks at 1932 and
      1902 cm(-)(1), the latter of which diminishes at alkaline pD and is assignable to
      a strong hydrogen-bonded state. It is most probable that the imidazolium side
      chain of His42 forms a strong hydrogen bond with CO, giving a His42 peak at 1388
      cm(-)(1) and a CO peak at 1902 cm(-)(1), in one conformer. The other hydrogen
      bonding state of His42, giving the 1408 cm(-)(1) peak, is ascribed to another
      conformer forming a medium-to-weak hydrogen bond with a water molecule in the
      distal cavity. The present finding that His42 can act as a strong proton donor to
      CO and decrease the CO bond order is consistent with the role of His42 as a
      general acid to cleave the O-O bond of hydrogen peroxide, a specific oxidizing
      agent, in the catalytic cycle of HRP.

PMID- 16893169
TI  - A new paradigm for DNA polymerase specificity.
AB  - We show that T7 DNA polymerase exists in three distinct structural states, as
      reported by a conformationally sensitive fluorophore attached to the recognition
      (fingers) domain. The conformational change induced by a correct nucleotide
      commits the substrate to the forward reaction, and the slow reversal of the
      conformational change eliminates the rate of the chemistry step from any
      contribution toward enzyme specificity. Discrimination against mismatches is
      enhanced by the rapid release of mismatched nucleotides from the ternary
      E.DNA.deoxynucleoside triphosphate complex and by the use of substrate-binding
      energy to actively misalign catalytic residues to reduce the rate of
      misincorporation. Our refined model for enzyme selectivity extends traditional
      thermodynamic formalism by including substrate-induced structural alignment or
      misalignment of catalytic residues as a third dimension on the free-energy
      profile and by including the rate of substrate dissociation as a key kinetic
      parameter.

PMID- 16893168
TI  - Position of synaptotagmin I at the membrane interface: cooperative interactions
      of tandem C2 domains.
AB  - Synaptotagmin I is a synaptic vesicle associated membrane protein that appears to
      regulate Ca(2+)-mediated exocytosis. Here, the Ca(2+)-dependent membrane
      interactions of a water soluble fragment of synaptotagmin I (C2AB) that contains
      its two C2 domains (C2A and C2B) were determined using site-directed spin
      labeling. Membrane depth parameters were obtained for 19 spin-labeled mutants of
      C2AB when bound to phosphatidylcholine and phosphatidylserine membranes, and
      these distance constraints were used in combination with the high-resolution
      structures of C2A and C2B to generate a model for the membrane orientation and
      position of synaptotagmin at the bilayer interface. Both C2A and C2B bind to the
      membrane interface with their first and third Ca(2+) binding loops penetrating
      the membrane interface. The polybasic face of C2B does not interact with the
      membrane lipid but is available for electrostatic interaction with other
      components of the fusion machinery. When compared to positions determined
      previously for the isolated domains, both C2A and C2B have similar orientations;
      however, the two domains are positioned deeper into the bilayer interior when
      present in the tandem construct. These data indicate that C2A and C2B do not act
      independently but influence their mutual membrane penetration. This may explain
      the occurrence of multiple C2 domains in proteins that function in membrane
      trafficking and repair.

PMID- 16893170
TI  - The Heliothis virescens cadherin protein expressed in Drosophila S2 cells
      functions as a receptor for Bacillus thuringiensis Cry1A but not Cry1Fa toxins.
AB  - Genetic knockout of the BtR4 gene encoding the Heliothis virescens cadherin-like
      protein (HevCaLP) is linked to resistance against Cry1Ac toxin from Bacillus
      thuringiensis. However, the functional Cry1Ac receptor role of this protein has
      not been established. We previously proposed HevCaLP as a shared binding site for
      B. thuringiensis (Bt) Cry1A and Cry1Fa toxins in the midgut epithelium of H.
      virescens larvae. Considering that Cry1Ac and Cry1Fa are coexpressed in second
      generation transgenic cotton for enhanced control of Heliothine and Spodoptera
      species, our model suggests the possibility of evolution of cross resistance via
      alteration of HevCaLP. To test whether HevCaLP is a Cry1Ac and Cry1Fa receptor,
      HevCaLP was transiently expressed on the surface of Drosophila melanogaster
      Schneider 2 (S2) cells. Expressed HevCaLP bound [(125)I]Cry1A toxins under native
      (dot blot) and denaturing (ligand blot) conditions. Affinity pull-down assays
      demonstrated that Cry1Fa does not bind to HevCaLP expressed in S2 cells or in
      solubilized brush border membrane proteins. Using a fluorescence-based approach,
      we tested the ability of expressed HevCaLP to mediate toxicity of Cry1A and
      Cry1Fa toxins. Cry1A toxins killed S2 cells expressing HevCaLP, whereas Cry1Fa
      toxin did not. Our results demonstrate that HevCaLP is a functional Cry1A but not
      Cry1Fa receptor.

PMID- 16893172
TI  - Spectroelectrochemical characterization of the [NiFe] hydrogenase of
      Desulfovibrio vulgaris Miyazaki F.
AB  - The active site in the [NiFe] hydrogenase of Desulfovibrio vulgaris Miyazaki F
      has been investigated by Fourier transform infrared (FTIR) spectroscopy. Analysis
      of the spectra allowed the three diatomic inorganic ligands to Fe in this enzyme
      to be identified as one CO molecule and two CN(-) molecules. Furthermore, pH
      dependent redox titrations were performed to determine the midpoint potentials as
      well as the pK value of the respective reactions and revealed that each single
      electron redox transition is accompanied by a single-proton transfer step. The
      comparison of these spectra with those published for other [NiFe] hydrogenases
      shows that the electronic structure of the active sites of these enzymes and
      their redox processes are essentially the same. Nevertheless, differences with
      respect to the frequency of the CO band and the pH dependence of the Ni-R states
      have been observed. Finally, the frequency shifts of the bands in the IR spectra
      were interpreted with respect to the electronic configuration of the redox
      intermediates in the catalytic cycle.

PMID- 16893171
TI  - Kinetic and structural evidence for the importance of Tyr236 for the integrity of
      the Mo active site in a bacterial sulfite dehydrogenase.
AB  - The sulfite dehydrogenase from Starkeya novella is the only known sulfite
      oxidizing enzyme that forms a permanent heterodimeric complex between a
      molybdenum and a heme c-containing subunit and can be crystallized in an electron
      transfer competent conformation. Tyr236 is a highly conserved active site residue
      in sulfite oxidoreductases and has been shown to interact with a nearby arginine
      and a molybdenum-oxo ligand that is involved in catalysis. We have created a
      Tyr236 to Phe substitution in the SorAB sulfite dehydrogenase. The purified
      SDH(Y236F) protein has been characterized in terms of activity, structure,
      intramolecular electron transfer, and EPR properties. The substituted protein
      exhibited reduced turnover rates and substrate affinity as well as an altered
      reactivity toward molecular oxygen as an electron acceptor. Following reduction
      by sulfite and unlike SDH(WT), the substituted enzyme was reoxidized quickly in
      the presence of molecular oxygen, a process reminiscent of the reactions of the
      sulfite oxidases. SDH(Y236F) also exhibited the pH-dependent CW-EPR signals that
      are typically observed in vertebrate sulfite oxidases, allowing a direct link of
      CW-EPR properties to changes caused by a single-amino acid substitution. No
      quantifiable electron transfer was seen in laser flash photolysis experiments
      with SDH(Y236F). The crystal structure of SDH(Y236F) clearly shows that as a
      result of the substitution the hydrogen bonding network surrounding the active
      site is disturbed, resulting in an increased mobility of the nearby arginine.
      These disruptions underline the importance of Tyr236 for the integrity of the
      substrate binding site and the optimal alignment of Arg55, which appears to be
      necessary for efficient electron transfer.

PMID- 16893173
TI  - Increases in calmodulin abundance and stabilization of activated inducible nitric
      oxide synthase mediate bacterial killing in RAW 264.7 macrophages.
AB  - The rapid activation of macrophages in response to bacterial antigens is central
      to the innate immune system that permits the recognition and killing of pathogens
      to limit infection. To understand regulatory mechanisms underlying macrophage
      activation, we have investigated changes in the abundance of calmodulin (CaM) and
      iNOS in response to the bacterial cell wall component lipopolysaccharide (LPS)
      using RAW 264.7 macrophages. Critical to these measurements was the ability to
      differentiate free iNOS from the CaM-bound (active) form of iNOS associated with
      nitric oxide generation. We observe a rapid 2-fold increase in CaM abundance
      during the first 30 min that is blocked by inhibition of either NFkappaB nuclear
      translocation or protein synthesis. A similar 2-fold increase in the abundance of
      the complex between CaM and iNOS is observed with the same time dependence. In
      contrast, there are no detectable increases in the CaM-free (i.e., inactive) form
      of iNOS within the first 2 h; it remains at a very low abundance during the
      initial phase of macrophage activation. Increasing cellular CaM levels in stably
      transfected macrophages results in a corresponding increase in the abundance of
      the CaM/iNOS complex that promotes effective bacterial killing following
      infection by Salmonella typhimurium. Thus, LPS-dependent increases in CaM
      abundance function in the stabilization and activation of iNOS on the rapid time
      scale associated with macrophage activation and bacterial killing. These results
      explain how CaM and iNOS coordinately function to form a stable complex that is
      part of a rapid host response that functions within the first 30 min following
      bacterial infection to upregulate the innate immune system involving macrophage
      activation.

PMID- 16893174
TI  - Drosophila nuclear receptor E75 is a thiolate hemoprotein.
AB  - Drosophila E75 is a member of the nuclear receptor superfamily. These eukaryotic
      transcription factors are involved in almost all physiological processes. They
      regulate transcription in response to binding of rigid hydrophobic hormone
      ligands. As it is the case for many nuclear receptors, the E75 hormone ligand was
      originally unknown. Recently, however, it was shown that the ligand binding
      domain (LBD) of E75 contains a tightly bound heme prosthetic group and is gas
      responsive. Here we have used site-directed mutagenesis along with UV-visible and
      electron paramagnetic resonance (EPR) spectroscopies to characterize and assign
      the heme iron axial ligands in E75. The F370Y mutation and addition of hemin to
      the growth medium during expression of the protein in Escherichia coli were
      necessary to produce good yields of heme-enriched E75 LBD. EPR studies revealed
      the presence of several species containing a strongly iron bound thiolate. The
      involvement of cysteines 396 and 468 in heme binding was subsequently shown by
      single and double mutations. Using a similar approach, we have also established
      that the sixth iron ligand of a well-defined coordination conformation, which
      accounts for approximately half of the total species, is histidine 574. The other
      iron coordination pairs are discussed. We conclude that E75 is a new example of a
      thiolate hemoprotein and that it may be involved in hormone synthesis regulation.

PMID- 16893175
TI  - Role of phenylalanine B10 in plant nonsymbiotic hemoglobins.
AB  - All plants contain an unusual class of hemoglobins that display bis-histidyl
      coordination yet are able to bind exogenous ligands such as oxygen. Structurally
      homologous hexacoordinate hemoglobins (hxHbs) are also found in animals
      (neuroglobin and cytoglobin) and some cyanobacteria, where they are thought to
      play a role in free radical scavenging or ligand sensing. The plant hxHbs can be
      distinguished from the others because they are only weakly hexcacoordinate in the
      ferrous state, yet no structural mechanism for regulating hexacoordination has
      been articulated to account for this behavior. Plant hxHbs contain a conserved
      Phe at position B10 (Phe(B10)), which is near the reversibly coordinated distal
      His(E7). We have investigated the effects of Phe(B10) mutation on kinetic and
      equilibrium constants for hexacoordination and exogenous ligand binding in the
      ferrous and ferric oxidation states. Kinetic and equilibrium constants for
      hexacoordination and ligand binding along with CO-FTIR spectroscopy, midpoint
      reduction potentials, and the crystal structures of two key mutant proteins (F40W
      and F40L) reveal that Phe(B10) is an important regulatory element in
      hexacoordination. We show that Phe at this position is the only amino acid that
      facilitates stable oxygen binding to the ferrous Hb and the only one that
      promotes ligand binding in the ferric oxidation states. This work presents a
      structural mechanism for regulating reversible intramolecular coordination in
      plant hxHbs.

PMID- 16893176
TI  - Conversion of protein farnesyltransferase to a geranylgeranyltransferase.
AB  - Posttranslational modifications are essential for the proper function of a number
      of proteins in the cell. One such modification, the covalent attachment of a
      single isoprenoid lipid (prenylation), is carried out by the CaaX
      prenyltransferases, protein farnesyltransferase (FTase) and protein
      geranylgeranyltransferase type-I (GGTase-I). Substrate proteins of these two
      enzymes are involved in a variety of cellular functions but are largely
      associated with signal transduction. These modified proteins include members of
      the Ras superfamily, heterotrimeric G-proteins, centromeric proteins, and a
      number of proteins involved in nuclear integrity. Although FTase and GGTase-I are
      highly homologous, they are quite selective for their substrates, particularly
      for their isoprenoid diphosphate substrates, FPP and GGPP, respectively. Here, we
      present both crystallographic and kinetic analyses of mutants designed to explore
      this isoprenoid specificity and demonstrate that this specificity is dependent
      upon two enzyme residues in the beta subunits of the enzymes, W102beta and
      Y365beta in FTase (T49beta and F324beta, respectively, in GGTase-I).

PMID- 16893177
TI  - Mammalian alkaline phosphatase catalysis requires active site structure
      stabilization via the N-terminal amino acid microenvironment.
AB  - In mammalian alkaline phosphatase (AP) dimers, the N-terminus of one monomer
      embraces the other, stretching toward its active site. We have analyzed the role
      of the N-terminus and its microenvironment in determining the enzyme stability
      and catalysis using human placental (PLAP) and tissue-nonspecific AP (TNAP) as
      paradigms. Deletion of nine amino acid (aa) residues in PLAP reduced its AP
      activity and heat stability, while deletion of 25 aa resulted in an inactive
      enzyme. In turn, deletion of five and nine N-terminal aa in TNAP reduced and
      abolished AP activity, respectively. The N-terminal aa deletions in both isozymes
      affected the rate of substrate catalysis (k(cat)), with an only minor effect on
      the Michaelis constant (K(m)) explained by decelerated intramolecular transition
      rates in the active site. Arg370 in PLAP, and the corresponding Arg374 in TNAP,
      critically control the structure and function of the enzymes, but the Glu6-Arg370
      bond predicted by the PLAP crystal structure appeared to be irrelevant with
      respect to PLAP stability or catalysis. Structural disruption was also noted in
      [R374A]TNAP, [Delta5]TNAP, [Delta9]TNAP, and [Delta25]TNAP using a panel of 19
      anti-TNAP antibodies illustrating the structural role of the N-terminus. Our data
      reveal that the N-terminal alpha-helical folding is more crucial for the
      structural stability of the second monomer in TNAP than in PLAP. The correct
      folding of the N-terminus and of interacting loops in its immediate environment
      is essential for overall structural integrity and for execution of intramolecular
      transitions during enzyme catalysis. These findings provide a mechanistic
      interpretation for loss-of-function mutations of N-terminal TNAP residues in
      cases of hypophosphatasia.

PMID- 16893178
TI  - The location of an engineered inter-subunit disulfide bond in factor for
      inversion stimulation (FIS) affects the denaturation pathway and cooperativity.
AB  - Two crossed-linked variants of the homodimeric DNA binding protein factor for
      inversion stimulation (FIS) were created via engineering of single intermolecular
      disulfide bonds. The conservative S30C and the nonconservative V58C FIS
      independent mutations resulted in FIS crossed-linked at the A helix (C30-C30) and
      at the middle of the B helix (C58-C58). This study sought to investigate how the
      location of an intermolecular disulfide bond may determine the effect on
      stability and its propagation through the structure to preserve or alter the
      denaturation cooperativity of FIS. The oxidized and reduced S30C and V58C FIS
      exhibited a far-UV CD spectrum and DNA binding affinities that were similar to WT
      FIS, indicating no significant changes in secondary and tertiary structure.
      However, the reduced and oxidized forms of the mutants revealed significant
      differences in the stability and equilibrium denaturation mechanism between the
      two mutants. In the reduced state, S30C FIS had very little effect on FIS
      stability, whereas V58C FIS was 2-3 kcal/mol less stable than WT FIS.
      Interestingly, while both disulfide bonds significantly increased the resistance
      to urea- and guanidine hydrochloride (GuHCl)-induced denaturation, oxidized V58C
      FIS exhibited a three-state GuHCl-induced transition. In contrast, oxidized S30C
      FIS displayed a highly cooperative WT-like transition with both denaturants. The
      three-state denaturation mechanism of oxidized V58C FIS induced by the GuHCl salt
      was reproduced by urea denaturation at pH 4, suggesting that disruption of a C
      terminus salt-bridge network is responsible for the loss of denaturation
      cooperativity of V58C FIS in GuHCl or urea, pH 4. A second mutation on V58C FIS
      created to place a single tryptophan probe (Y95W) at the C-terminus further
      implies that the denaturation intermediate observed in disulfide crossed-linked
      V58C FIS results from a decoupling of the stabilities of the C-terminus and the
      rest of the protein. These results show that, unlike the C30-C30 intermolecular
      disulfide bond, the C58-C58 disulfide bond did not evenly stabilize the FIS
      structure, thereby highlighting the importance of the location of an engineered
      disulfide bond on the propagation of stability and the denaturation cooperativity
      of a protein.

PMID- 16893179
TI  - Mode of inhibitory action of Deltalac-acetogenins, a new class of inhibitors of
      bovine heart mitochondrial complex I.
AB  - We have revealed that Deltalac-acetogenins, a new class of inhibitors of bovine
      heart mitochondrial complex I (NADH-ubiquinone oxidoreductase), act differently
      from ordinary inhibitors such as rotenone and piericidin A [Ichimaru et al.
      (2005) Biochemistry 44, 816-825]. Since a detailed study of these unique
      inhibitors might provide new insight into the terminal electron transfer step of
      the enzyme, we further characterized their inhibitory action using the most
      potent Deltalac-acetogenin derivative (compound 1). Unlike ordinary complex I
      inhibitors, 1 had a dose-response curve for inhibition of the reduction of
      exogenous short-chain ubiquinones that was difficult to explain with a simple
      bimolecular association model. The inhibitory effect of 1 on ubiquinol-NAD(+)
      oxidoreductase activity (reverse electron transfer) was much weaker than that on
      NADH oxidase activity (forward electron transfer), indicating a direction
      specific effect. These results suggest that the binding site of 1 is not
      identical to that of ubiquinone and the binding of 1 to the enzyme secondarily
      (or indirectly) disturbs the redox reaction of ubiquinone. Using endogenous and
      exogenous ubiquinone as an electron acceptor of complex I, we investigated the
      effect of 1 in combination with different ordinary inhibitors on the superoxide
      production from the enzyme. The results indicated that the level of superoxide
      production induced by 1 is significantly lower than that induced by ordinary
      inhibitors probably because of fewer electron leaks from the ubisemiquinone
      radical to molecular oxygen and that the site of inhibition by 1 is downstream of
      that by ordinary inhibitors. The unique inhibitory action of hydrophobic Deltalac
      acetogenins may be closely associated with the dynamic function of the membrane
      domain of complex I.

PMID- 16893180
TI  - Structural and functional comparisons of nucleotide
      pyrophosphatase/phosphodiesterase and alkaline phosphatase: implications for
      mechanism and evolution.
AB  - The rapid expansion of the amount of genomic and structural data has provided
      many examples of enzymes with evolutionarily related active sites that catalyze
      different reactions. Functional comparisons of these active sites can provide
      insight into the origins of the enormous catalytic proficiency of enzymes and the
      evolutionary changes that can lead to different enzyme activities. The alkaline
      phosphatase (AP) superfamily is an ideal system to use in making such comparisons
      given the extensive data available on both nonenzymatic and enzymatic phosphoryl
      transfer reactions. Some superfamily members, such as AP itself, preferentially
      hydrolyze phosphate monoesters, whereas others, such as nucleotide
      pyrophosphatase/phosphodiesterase (NPP), preferentially hydrolyze phosphate
      diesters. We have measured rate constants for NPP-catalyzed hydrolysis of
      phosphate diesters and monoesters. NPP preferentially catalyzes diester
      hydrolysis by factors of 10(2)-10(6), depending on the identity of the diester
      substrate. To identify features of the NPP active site that could lead to
      preferential phosphate diester hydrolysis, we have determined the structure of
      NPP in the absence of ligands and in complexes with vanadate and AMP. Comparisons
      to existing structures of AP reveal bimetallo cores that are structurally
      indistinguishable, but there are several distinct structural features outside of
      the conserved bimetallo site. The structural and functional data together suggest
      that some of these distinct functional groups provide specific substrate binding
      interactions, whereas others tune the properties of the bimetallo active site
      itself to discriminate between phosphate diester and monoester substrates.

PMID- 16893181
TI  - Reactivity-based analysis of domain structures in native replication protein A.
AB  - Replication protein A (RPA) is an essential heterotrimeric ssDNA binding protein
      that participates in DNA repair, replication, and recombination. Though X-ray and
      NMR experiments have been used to determine three-dimensional structure models of
      the protein's domain fragments, a complete RPA structural model has not been
      reported. To test whether the fragment structures faithfully represent the same
      portions in the native solution-state protein, we have examined the structure of
      RPA under biologically relevant conditions. We have probed the location of
      multiple amino acids within the native RPA three-dimensional structure using
      reactivity of these amino acids toward proteolytic and chemical modification
      reagents. In turn, we evaluated different structural models by comparing the
      observed native RPA reactivities with anticipated reactivities based on candidate
      structural models. Our results show that our reactivity analysis approach is
      capable of critically assessing structure models and can be a basis for selecting
      the most relevant from among alternate models of a protein structure. Using this
      analytical approach, we verified the relevance of RPA fragment models to the
      native protein structure. Our results further indicate several important features
      of native RPA's structure in solution, such as flexibility at specific locations
      in RPA, particularly in the C-terminal region of RPA70. Our findings are
      consistent with reported DNA-free structural models and support the role of
      conformational change in the ssDNA binding mechanism of RPA.

PMID- 16893182
TI  - Interpreting oligonucleotide microarray data to determine RNA secondary
      structure: application to the 3' end of Bombyx mori R2 RNA.
AB  - A method to deduce RNA secondary structure on the basis of data from microarrays
      of 2'-O-methyl RNA 9-mers immobilized in agarose film on glass slides is tested
      with a 249 nucleotide RNA from the 3' end of the R2 retrotransposon from Bombyx
      mori. Various algorithms incorporating binding data and free-energy minimization
      calculations were compared for interpreting the data to provide possible
      secondary structures. Two different methods give structures with 100 and 87% of
      the base pairs determined by sequence comparison. In contrast, structures
      predicted by free-energy minimization alone by Mfold and RNAstructure contain 52
      and 72% of the known base pairs, respectively. This combination of high
      throughput microarray techniques with algorithms using free-energy calculations
      has potential to allow for fast determination of RNA secondary structure. It
      should also facilitate the design of antisense and siRNA oligonucleotides.

PMID- 16893183
TI  - Interaction of cardiac troponin C with calmodulin antagonist [corrected] W7 in
      the presence of three functional regions of cardiac troponin I.
AB  - W7 is a well-known calmodulin (CaM) antagonist and has been implicated as an
      inhibitor of the troponin C-mediated Ca(2+) activation of cardiac muscle
      contraction. In this study, we use NMR spectroscopy to study binding of W7 to
      cardiac troponin C (cTnC) free or in complex with cardiac troponin I (cTnI)
      peptides. Titration of cTnC.3Ca(2+) with W7 shows that residues throughout the
      sequence, including the N- and C-domains of cTnC and the central linker, are
      affected. Analysis of the binding stoichiometry and the trajectories of chemical
      shift changes indicate that W7 binding occurs at multiple sites. To address the
      issue of whether multiple-site binding is relevant within the troponin complex,
      W7 is titrated to a cTnC-cTnI complex (cTnC.3Ca(2+).cTnI(34)(-)(71).cTnI(128)(
      )(163)). In the presence of the N-terminal (residues approximately 34-71),
      inhibitory (residues approximately 128-147), and switch (residues approximately
      147-163) regions of cTnI, W7 induces chemical shift changes only in the N-domain
      and not in the C-domain or the central linker of cTnC. The results indicate that
      in the presence of cTnI, W7 no longer binds to multiple sites of cTnC but instead
      binds specifically to the N-domain, and the binding (K(D) = 0.5 +/- 0.1 mM) can
      occur together with the switch region of cTnI. Hence, W7 may play a role in
      directly modulating the Ca(2+) sensitivity of the regulatory domain of cTnC and
      the interaction of the switch region of cTnI and cTnC.

PMID- 16893184
TI  - Characterization of the backbone and side chain dynamics of the CaM-CaMKIp
      complex reveals microscopic contributions to protein conformational entropy.
AB  - Calmodulin is a central mediator of calcium-dependent signal transduction
      pathways and regulates the activity of a large number of diverse targets. Calcium
      dependent interactions of calmodulin with regulated proteins are of generally
      high affinity but of quite variable thermodynamic origins. Here we investigate
      the influence of the binding of the calmodulin-binding domain of calmodulin
      kinase I on the fast internal dynamics of calcium-saturated calmodulin. NMR
      relaxation was used to probe motion on the backbone (viewed through the backbone
      amide NH group) and the side chains (viewed through methyl groups). The
      distribution of the amplitudes of side chain dynamics is trimodal. The
      microscopic details of side chain motion are compared with those of a
      thermodynamically and structurally similar complex of calmodulin with the
      calmodulin-binding domain of the smooth muscle myosin light chain kinase. While
      there are no significant differences in backbone dynamics and no net change in
      methyl-bearing side chain dynamics, a large redistribution of the amplitude of
      methyl dynamics is observed between the two complexes. The variation in dynamics
      was largely localized to the heterogeneously dynamic target-binding interface,
      suggesting that differential dynamics of the binding surface plays a functional
      role in the high-affinity binding interactions of calmodulin. These results begin
      to reveal a fundamental role for residual protein entropy in molecular
      recognition by calmodulin.

PMID- 16893185
TI  - Analysis of single Alzheimer solid plaque cores by laser capture microscopy and
      nanoelectrospray/tandem mass spectrometry.
AB  - Aggregation of the 40-42 residue amyloid beta-peptide (Abeta) into amyloid
      plaques is a central event in Alzheimer's disease (AD) pathogenesis. Many
      proteins have by immunohistochemical techniques been shown to codeposit with
      Abeta in AD plaques. It is possible that some of these could seed Abeta
      aggregation and therefore be found in the actual core of the plaque. Here, we
      present a highly sensitive method for unbiased biochemical analysis of plaque
      cores. A mild purification protocol based on centrifugation and filtration was
      used to purify intact plaque cores from human AD brain. The purified plaques were
      dispensed on a glass slide and viewed in a laser capture microscope, and plaque
      cores were catapulted into a tube cap by a laser beam. After dissolution in
      formic acid, plaques were digested and analyzed by liquid chromatography coupled
      online to electrospray/tandem mass spectrometry. One single plaque was found to
      be sufficient for positive identification of the main amyloid component.
      Remarkably, Abeta was the only protein identified when 200 plaques were isolated
      and analyzed with the present method. Thus, it is possible that no proteins
      copolymerize with Abeta in the plaque cores and that Abeta alone is sufficient
      for formation of plaque cores. In support of this notion, core-like structures
      were observed after incubation of synthetic Abeta for 2 weeks. We suggest that
      the method described here could be used for the general analysis of amyloid
      aggregates and inclusion bodies found in other neurodegenerative disorders and
      that plaque cores in AD brain are molecularly homogeneous structures.

PMID- 16893186
TI  - B-myc: N-terminal recognition of myc binding proteins.
AB  - B-Myc is an endogenous, N-terminal homologue of transcription factor c-Myc that
      lacks the C-terminal DNA binding and protein dimerization domain of c-Myc.
      Clinical mutations in the c-Myc N-terminal region, and the subsequent
      misregulation of Myc, are implicated in the development of numerous human
      cancers. Myc functions to both activate and repress transcription by associating
      with multiple binding partners. We investigated the structural and dynamical
      properties of B-Myc, free or associated with the transactivation inhibitor, MM-1,
      and the activator, TBP, using NMR spectroscopy. B-Myc has no persistent tertiary
      structure, yet regions corresponding to Myc homology boxes 1 and 2 (MBI and MBII,
      respectively) have molten globule-like characteristics. B-Myc binds to MM-1 in a
      specific manner without becoming highly structured. The local regions of B-Myc
      involved in binding differ for MM-1 and TBP, and regions not identified by
      mutagenesis are found to be involved in MM-1 binding. The results provide new
      insights into Myc N-terminal protein-protein interactions. We propose a model for
      Myc regulation through differential involvement of MBI and MBII in the binding of
      Myc interacting proteins.

PMID- 16893188
TI  - Structure-based analysis of the beta8 interactive sequence of human alphaB
      crystallin.
AB  - The functional importance of the beta8 sequence ((131)LTITSSLS(138)), which is on
      the surface of the alpha crystallin core domain of human alphaB crystallin, was
      evaluated using site-directed mutagenesis. Ultraviolet circular dichroism
      determined that mutating the surface-exposed, nonconserved residues, Leu-131, Thr
      132, Thr-134, Ser-135, Ser-136, and Ser-138 individually or in combination
      (alphaAbeta8 and CEbeta8), had no measurable effect on secondary and tertiary
      structure. Size exclusion chromatography determined the size of the complexes
      formed by the beta8 mutants to be 6-8 subunits larger than wt alphaB crystallin.
      In chaperone assays, the protective effect of the L131S, T132A, and S135C mutants
      of the beta8 sequence was similar to wt alphaB crystallin when beta(L) crystallin
      and alcohol dehydrogenase were the chaperone substrates and decreased to 66% when
      citrate synthase was the chaperone substrate. In contrast, the chaperone activity
      for all three substrates was dramatically reduced for the T134K, S138A, S136H,
      and CEbeta8 mutants. The prominent location of Thr-134, Ser-136, and Ser-138 on
      the exposed surface of the alpha crystallin core domain could account for the
      effect on complex assembly and chaperone activity. Modulation of chaperone
      activity by the exposed residues of the beta8 sequence in the alpha crystallin
      core domain was independent of complex size. The results established the beta3
      beta8-beta9 surface of the alpha crystallin core domain as an interface for
      complex assembly and chaperone activity.

PMID- 16893187
TI  - Structure and interactions of the ubiquitin-conjugating enzyme variant human
      Uev1a: implications for enzymatic synthesis of polyubiquitin chains.
AB  - Lys(63)-linked polyubiquitination of TRAF2 or TRAF6 is an essential step within
      the signal transduction cascade responsible for activation of p38, c-Jun N
      terminal kinase, and the transcription factor NF-kappaB. Attachment of ubiquitin
      (Ub) to a TRAF, and conjugation of Ub molecules to form a polyUb chain, is
      catalyzed by a heterodimer composed of a catalytically active E2 (hUbc13),
      involved in covalent bond transfer, and hUev1a, an E2-like protein involved in
      substrate Ub binding. Given the key biochemical processes in which hUev1a is
      involved, it is important to determine the molecular basis of the catalytic
      mechanism for Lys(63)-linked protein ubiquitination. Nuclear magnetic resonance
      (NMR) spectroscopy was used to determine the structure of hUev1a and its
      interactions with Ub and hUbc13. A structural model for the Ub-hUev1a-hUbc13-Ub
      tetramer was developed to gain chemical insight into the synthesis of Lys(63)
      linked Ub chains. We propose that a network of hydrogen bonds involving hUbc13
      Asp(81) and Ub-Glu(64) positions Ub-Lys(63) proximal to the active site.
      Interestingly, restrained molecular dynamics simulations in implicit solvent
      indicate that deprotonation of Ub-Lys(63) does not involve a general Asp or Glu
      base and may occur when the amino group approaches the thioester carbonyl carbon
      near the Burgi-Dunitz trajectory.

PMID- 16893189
TI  - Characterization of a covalently linked yeast cytochrome c-cytochrome c
      peroxidase complex: evidence for a single, catalytically active cytochrome c
      binding site on cytochrome c peroxidase.
AB  - A covalent complex between recombinant yeast iso-1-cytochrome c and recombinant
      yeast cytochrome c peroxidase (rCcP), in which the crystallographically defined
      cytochrome c binding site [Pelletier, H., and Kraut, J. (1992) Science 258, 1748
      1755] is blocked, was synthesized via disulfide bond formation using specifically
      engineered cysteine residues in both yeast iso-1-cytochrome c and yeast
      cytochrome c peroxidase [Papa, H. S., and Poulos, T. L. (1995) Biochemistry 34,
      6573-6580]. Previous studies on similar covalent complexes, those that block the
      Pelletier-Kraut crystallographic site, have demonstrated that samples of the
      covalent complexes have detectable activities that are significantly lower than
      those of wild-type yCcP, usually in the range of approximately 1-7% of that of
      the wild-type enzyme. Using gradient elution procedures in the purification of
      the engineered peroxidase, cytochrome c, and covalent complex, along with
      activity measurements during the purification steps, we demonstrate that the
      residual activity associated with the purified covalent complex is due to
      unreacted CcP that copurifies with the covalent complex. Within experimental
      error, the covalent complex that blocks the Pelletier-Kraut site has zero
      catalytic activity in the steady-state oxidation of exogenous yeast iso-1
      ferrocytochrome c by hydrogen peroxide, demonstrating that only ferrocytochrome c
      bound at the Pelletier-Kraut site is oxidized during catalytic turnover.

PMID- 16893190
TI  - Characterization of heme-regulated eIF2alpha kinase: roles of the N-terminal
      domain in the oligomeric state, heme binding, catalysis, and inhibition.
AB  - Heme-regulated eIF2alpha kinase [heme-regulated inhibitor (HRI)] plays a critical
      role in the regulation of protein synthesis by heme iron. The kinase active site
      is located in the C-terminal domain, whereas the N-terminal domain is suggested
      to regulate catalysis in response to heme binding. Here, we found that the rate
      of dissociation for Fe(III)-protoporphyrin IX was much higher for full-length HRI
      (1.5 x 10(-)(3) s(-)(1)) than for myoglobin (8.4 x 10(-)(7) s(-)(1)) or the alpha
      subunit of hemoglobin (7.1 x 10(-)(6) s(-)(1)), demonstrating the heme-sensing
      character of HRI. Because the role of the N-terminal domain in the structure and
      catalysis of HRI has not been clear, we generated N-terminal truncated mutants of
      HRI and examined their oligomeric state, heme binding, axial ligands, substrate
      interactions, and inhibition by heme derivatives. Multiangle light scattering
      indicated that the full-length enzyme is a hexamer, whereas truncated mutants
      (truncations of residues 1-127 and 1-145) are mainly trimers. In addition, we
      found that one molecule of heme is bound to the full-length and truncated mutant
      proteins. Optical absorption and electron spin resonance spectra suggested that
      Cys and water/OH(-) are the heme axial ligands in the N-terminal domain-truncated
      mutant complex. We also found that HRI has a moderate affinity for heme, allowing
      it to sense the heme concentration in the cell. Study of the kinetics showed that
      the HRI kinase reaction follows classical Michaelis-Menten kinetics with respect
      to ATP but sigmoidal kinetics and positive cooperativity between subunits with
      respect to the protein substrate (eIF2alpha). Removal of the N-terminal domain
      decreased this cooperativity between subunits and affected the other kinetic
      parameters including inhibition by Fe(III)-protoporphyrin IX, Fe(II)
      protoporphyrin IX, and protoporphyrin IX. Finally, we found that HRI is inhibited
      by bilirubin at physiological/pathological levels (IC(50) = 20 microM). The roles
      of the N-terminal domain and the binding of heme in the structural and functional
      properties of HRI are discussed.

PMID- 16893191
TI  - N-Methylated peptide inhibitors of beta-amyloid aggregation and toxicity.
      Optimization of the inhibitor structure.
AB  - The key pathogenic event in the onset of Alzheimer's disease (AD) is believed to
      be the aggregation of the beta-amyloid (Abeta) peptide into toxic oligomers.
      Molecules that interfere with this process may therefore act as therapeutic
      agents for the treatment of AD. N-Methylated peptides (meptides) are a general
      class of peptide aggregation inhibitors that act by binding to one face of the
      aggregating peptide but are unable to hydrogen bond on the other face, because of
      the N-methyl group replacing a backbone NH group. Here, we optimize the structure
      of meptide inhibitors of Abeta aggregation, starting with the KLVFF sequence that
      is known to bind to Abeta. We varied the meptide length, N-methylation sites,
      acetylation, and amidation of the N and C termini, side-chain identity, and
      chirality, via five compound libraries. Inhibitor activity was tested by
      thioflavin T binding, affinity chromatography, electron microscopy, and an 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide toxicity assay. We found
      that inhibitors should have all d chirality, have a free N terminus but an
      amidated C terminus, and have large, branched hydrophobic side chains at
      positions 1-4, while the side chain at position 5 was less important. A single N
      methyl group was necessary and sufficient. The most active compound, d-[(chGly)
      (Tyr)-(chGly)-(chGly)-(mLeu)]-NH(2), was more active than all previously reported
      peptide inhibitors. Its related non-N-methylated analogues were insoluble and
      toxic.

PMID- 16893192
TI  - Catalysis of covalent Lp(a) assembly: evidence for an extracellular enzyme
      activity that enhances disulfide bond formation.
AB  - The assembly of lipoprotein(a) (Lp(a)) particles occurs via a two-step mechanism
      in which noncovalent interactions between apolipoprotein(a) (apo(a)) and the
      apolipoproteinB-100 component of low density lipoprotein precede the formation of
      a single disulfide bond. Although we have previously demonstrated that the rate
      constant for the covalent step of Lp(a) assembly can be enhanced by altering the
      conformational status of apo(a), the resultant rates of covalent Lp(a) particle
      formation measured in vitro are relatively slow. The large excess of Lp(a) (over
      apo(a)) observed in vivo can be accounted for by a preferential clearance of
      apo(a) over Lp(a) and/or a sufficiently high rate of covalent Lp(a) assembly. In
      the present study, we report that cultured human hepatoma cells secrete an
      oxidase activity that dramatically enhances the rate of covalent Lp(a) assembly.
      This activity is likely possessed by a protein because it is heat-sensitive and
      is retained in the concentrate following ultrafiltration through a 5 kDa cutoff
      filter. However, a small molecule cofactor for the activity is suggested by the
      observation that the activity is lost upon dialysis. Plots of Lp(a) assembly rate
      versus input apo(a) concentration gave rectangular hyperbolae; the reaction
      displayed an unusual dependence on the concentration of apoB-100, with increasing
      concentrations of apoB-100 resulting in slower rates of Lp(a) assembly at low
      concentrations of apo(a), an effect that was alleviated by higher apo(a)
      concentrations. Interestingly, V(max(app))/K(m(app)) ratios were insensitive to
      apoB-100 concentration, which is diagnostic of a ping-pong reaction mechanism. In
      this way, the putative Lp(a) oxidase may be functionally analogous to protein
      disulfide isomerase, which exhibits a similar mechanism during the catalysis of
      disulfide bond formation during protein folding, although we have ruled out a
      role for this enzyme in Lp(a) assembly.

PMID- 16893193
TI  - Purification and ATP hydrolysis of the putative cholesterol transporters ABCG5
      and ABCG8.
AB  - Mutations in the ATP-binding cassette (ABC) transporters ABCG5 and ABCG8 lead to
      sitosterolemia, a disorder characterized by sterol accumulation and premature
      atherosclerosis. ABCG5 and ABCG8 are both half-size transporters that have been
      proposed to function as heterodimers in vivo. We have expressed the recombinant
      human ABCG5 and ABCG8 genes in the yeast Pichia pastoris and purified the
      proteins to near homogeneity. Purified ABCG5 and ABCG8 had very low ATPase
      activities (<5 nmol min(-)(1) mg(-)(1)), suggesting that expression of ABCG5 or
      ABCG8 alone yielded nonfunctional transporters. Coexpression of the two genes in
      P. pastoris greatly increased the yield of pure proteins, indicating that the two
      transporters stabilize each other during expression and purification. Copurified
      ABCG5/G8 displayed low but significant ATPase activity with a V(max) of
      approximately 15 nmol min(-)(1) mg(-)(1). The ATPase activity was not stimulated
      by sterols. The catalytic activity of copurified ABCG5/G8 was characterized in
      detail, demonstrating low affinity for MgATP, a preference for Mg as a metal
      cofactor and ATP as a hydrolyzed substrate, and a pH optimum near 8.0. AlFx and
      BeFx inhibited MgATP hydrolysis by specific trapping of nucleotides in the
      ABCG5/G8 proteins. Furthermore, ABCG5/G8 eluted as a dimer on gel filtration
      columns. The data suggest that the hetero-dimer is the catalytically active
      species, and likely the active species in vivo.

PMID- 16893194
TI  - Multiple isotope effect study of the hydrolysis of formamide by urease from jack
      bean (Canavalia ensiformis).
AB  - Multiple kinetic isotope effects have been measured for the urease-catalyzed
      hydrolysis of formamide at pH 6.0 and 25 degrees C. These kinetic isotope effects
      include the carbonyl-C ((13)k = 1.0241 +/- 0.0009), the carbonyl-O ((18)k =
      0.9960 +/- 0.0009), the formyl-H ((D)k = 0.95 +/- 0.01), the leaving-N ((15)k=
      1.0327 +/- 0.0006), and the nucleophile-O ((18)k = 0.9778 +/- 0.0005). In
      addition, the enzyme does not catalyze the exchange of oxygen from the solvent
      into the carbonyl-O of formamide or the product, formate ion. The isotope effects
      are consistent with the rate-determining collapse of the tetrahedral intermediate
      (i.e., C-N bond cleavage). The pH optimum for formamide is at pH 5.3, whereas for
      urea, it is near 8.0. This is best accommodated by the mechanism proposed by
      Hausinger and Karplus, in which an active site cysteine binds to the nonleaving
      nitrogen in urea. For urea, the preference is for the anionic form of the
      sulfhydryl; for formamide, the neutral form is preferred, leading to the lower pH
      optimum.

PMID- 16893195
TI  - Rapid fabrication of large-area colloidal crystal monolayers by a vortical
      surface method.
AB  - We have developed a simple approach for rapidly fabricating large-scale colloidal
      crystal arrays on substrates. Latex particles were first assembled into a close
      packed monolayer on a vortical water surface; the monolayer was then transferred
      onto substrates by a withdrawer. Such an assembly method is conceptually similar
      to the Langmuir-Blodgett (L-B) methods for film deposition but does not require
      an L-B trough. The samples exhibit a large-scale periodic feature based on
      optical microscopy and scanning electron microscopy observations and diffract the
      laser beam, acting as crystals. This newly developed technique is timesaving,
      widely accessible, and applicable to large particles (up to 2 microm). It
      promises to be useful in nanofabrication.

PMID- 16893196
TI  - In-situ incorporation of gold nanoparticles of desired sizes into three
      dimensional macroporous matrixes.
AB  - We present here a facile route to the incorporation of gold nanoparticles (GNPs)
      with desired sizes into three-dimensionally ordered macroporous (3DOM) matrixes.
      Our route combined the first attachment of small GNPs to the silica colloidal
      crystal templates as precursors and their subsequent controlled growth by the in
      situ chemical reduction method. The desired enlargement of GNPs was acquired via
      their alternating and repeated exposure to solutions of auric salts and reducing
      agent NH(3)OH. Such gold-decorated silica templates were also converted into self
      sustained polystyrene (PS) macroporous films with GNPs embedded in their wall
      structures. The growth of gold seeds can be easily followed by their UV-vis
      absorbance spectra. The route provides an alternative way to incorporate GNPs
      with predetermined sizes into 3DOM matrixes without destroying their ordered
      structures. A highlight of our approach is that it obviates the need for the
      preformation of various-sized GNPs, which is an indispensable step in many other
      approaches.

PMID- 16893197
TI  - Patterned arrays of au rings for localized surface plasmon resonance.
AB  - In this paper, we examined the characteristic behavior of localized surface
      plasmon resonances (LSPR) of Au dot and ring arrays in response to the selective
      binding of biomolecules. To do this, patterned arrays of Au rings and dots with
      various feature scales were fabricated over large areas by an imprint lithography
      technique. Our results showed that the LSPR spectra of the Au nanorings exhibited
      a blue shift with increase in the ring widths and asymptotically converged to
      those for Au nanodots. This clearly implies that the LSPR spectra can be tuned
      over an extended wavelength range by varying the ring width. For an illustrative
      purpose, the patterned Au structures were used to detect the binding of
      streptavidin to biotin. In doing this, the Au patterns were chemically modified
      with G4 dendrimers of amine terminated poly(amidoamine), which facilitated the
      tethering of biotin onto the Au pattern. Exposure of the biotinylated Au
      nanorings to aqueous streptavidin solution induced both red-shifts of the LSPR
      spectra and changes in the peak intensities. The sensitivity of the LSPR spectra
      to the binding of the biomolecules was enhanced as the ring width of Au rings was
      decreased.

PMID- 16893199
TI  - Adhesion of microcapsules.
AB  - The adhesion of microcapsules to an attractive contact potential is studied
      theoretically. The axisymmetric shape equations are solved numerically. Beyond a
      universal threshold strength of the potential, the contact radius increases in
      proportion to the square root of the strength. Scaling functions for the
      corresponding amplitudes are derived as a function of the elastic parameters.

PMID- 16893198
TI  - No intrinsic depletion layer on a polystyrene thin film at a water interface.
AB  - Using neutron reflectivity, we found that there is no intrinsic depletion layer
      at a deuterated polystyrene (dPS) film and deuterium oxide (D(2)O) interface. A
      spun-cast film is susceptible to contamination on its surface from its
      surroundings during sample preparation. A contamination layer of hydrogenated
      organic material will be detected as a reduced scattering length density layer at
      the interface. We demonstrate that, by careful treatment of the film,
      contamination would be the primary cause of the reduced scattering length density
      layer at the interface.

PMID- 16893200
TI  - Electronic structure of the surface of the ionic liquid [EMIM][Tf(2)N] studied by
      metastable impact electron spectroscopy (MIES), UPS, and XPS.
AB  - The near-surface electronic structure of the room-temperature ionic liquid (RT
      IL) 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide
      ([EMIM][Tf(2)N]) has been investigated with the combination of the electron
      spectroscopies metastable impact electron spectroscopy (MIES), ultraviolet
      photoelectron spectroscopy (UPS (HeI and HeII)), and monochromatized X-ray
      photoelectron spectroscopy (XPS). We find that the top of the valence band states
      originates from states of the cation (see also ref 1). The ultimately surface
      sensitive technique MIES proves that the surface layer consists of both cations
      and anions. The temperature dependence of the spectra has been measured between
      about 160 and 610 K. Information on the glass transition and the possibility for
      low-temperature distillation of [EMIM][Tf(2)N] at reduced pressures is derived
      from the present results.

PMID- 16893201
TI  - Reversible pattern formation through photolysis.
AB  - We report a photolytic method to induce spatial and temporal
      patterning/deposition of particles at the micron scale on a time scale of
      seconds. Reversible pattern formation by negatively charged particles occur
      around micron-sized silver features on different substrates when exposed to UV
      light in the presence of aqueous hydrogen peroxide. Diffusiophoretic motion due
      to a spatially defined ion gradient accounts for our observations. Atomic force
      and optical microscopy, as well as conductivity measurements, support this
      hypothesis.

PMID- 16893202
TI  - Rotation in suspension of a rod-shaped colloid.
AB  - The simple strategy of coating a closely packed colloid monolayer with a
      nanometer-thick metal film to connect colloidal spheres and then gently
      sonicating produces a series of colloid metastructures, including rods and planar
      sheets. These structures can be fluorescently labeled, which can serve as a probe
      to monitor their dynamics in complex environments. The metal coating modulates
      fluorescence emission as these structures rotate in suspension. By analyzing the
      time sequence of fluorescence images using single-particle tracking techniques,
      here we measure the rotational dynamics of a rodlike tetramer, quantifying
      rotation along the long axis.

PMID- 16893203
TI  - Functional organotrimethoxysilane derivative with strong intermolecular pi-pi
      interaction: one-pot grafting reaction on oxidized silicon substrates.
AB  - Although the fabrication of self-assembled monolayers (SAMs) on an oxidized
      silicon substrate with special functionality is an important topic for various
      applications, it is still very difficult to obtain a densely grafted monolayer.
      With a newly synthesized organotrimethoxysilane containing a 1-cyano-1,2
      bisbiphenyl-ethylene (CNMBE) moiety which provides a strong pi-pi intermolecular
      interaction, an SAM of well-ordered structure is readily obtained by a one-pot
      grafting reaction under mild conditions. The aggregation process of the CNMBE
      moiety, which induced a close packing of organosilane on the substrate, was
      visually monitored by the fluorescence of the monolayer grafted on quartz.

PMID- 16893204
TI  - Formation of anisotropic polymer colloids by disparate relaxation times.
AB  - We show that coupling between a fast and a slow relaxation time causes the
      spontaneous formation of protrusions in colloids made of cross-linked polymers.
      The volume of the protrusions can be controlled by adjusting the ratio between
      the relaxation times. This, in principle, results in particles with levels of
      anisotropy that can be made "to order".

PMID- 16893205
TI  - High-yield sol-gel synthesis of well-dispersed, colorless ZrO(2) nanocrystals.
AB  - A 93% high-yield synthesis of well-dispersed, colorless zirconium dioxide
      (ZrO(2)) nanocrystals is reported. In this synthesis, hydrolysis and condensation
      reactions of zirconium(IV) tert-butoxide in the presence of oleic acid (100
      degrees C) formed ZrO(2) precursors. The ZrO(2) precursors were made of -Zr-O-Zr-
      networks surrounded by oleic acid molecules. Annealing (280 degrees C) the
      precursors dispersed in dioctyl ether caused crystallization of the -Zr-O-Zr-
      networks, thereby generating 4 nm ZrO(2) nanocrystals stabilized with oleic acid.
      The particles were highly crystalline and tetragonal phase. A dense ZrO(2)
      nanocrystal dispersion in toluene (280 mg/mL) showed a transmittance of about 90%
      (3 mm optical path length) in the whole visible region.

PMID- 16893206
TI  - Synthesis of spongy gold nanocrystals with pronounced catalytic activities.
AB  - A simple and easier chemical method for preparing spongy gold nanocrystals has
      been developed on the basis of a modified-citrate reduction technique of the
      corresponding gold salt at 25 degrees C in the absence of template. These
      nanocrystals possessed autocatalytic behavior and exhibited pronounced catalytic
      activity in the borohydride reduction of 4-nitrophenol due to their unique spongy
      morphology.

PMID- 16893207
TI  - Dynamics of fracture in drying suspensions.
AB  - We investigate the dynamics of fracture in drying films of colloidal silica.
      Water loss quenches the nanoparticle dispersions to form a liquid-saturated
      elastic network of particles that relieves drying-induced strain by cracking.
      These cracks display intriguing intermittent motion originating from the
      deformation of arrested crack tips and aging of the elastic network. The dynamics
      of a single crack exhibits a universal evolution, described by a balance of the
      driving elastic power with the sum of interfacial power and the viscous
      dissipation rate of flowing interstitial fluid.

PMID- 16893208
TI  - Novel method for the estimation of the binding isotherms of ionic surfactants on
      oppositely charged polyelectrolytes.
AB  - One of the most important characteristics of the polyelectrolyte/surfactant
      interaction is the binding isotherm of the surfactant because it provides basic
      thermodynamic information about the binding mechanism. However, the amount of the
      surfactant bound to the polymer may crucially affect the surface properties of
      these systems via changing the thermodynamic activity of the components.
      Therefore, a knowledge of the binding isotherms can also be useful in tuning the
      efficiency of commercial products. However, the determination of these isotherms
      is still subject to significant experimental difficulties. In this letter, we
      offer a novel method for the estimation of binding isotherms based on
      electrokinetic measurements. The technique provides a simple and quick way to
      estimate the bound amount of surfactant that might be useful in both fundamental
      and industrial research. In principle, the proposed method could also be extended
      to the determination of the binding isotherms of small ligands on
      biomacromolecules.

PMID- 16893209
TI  - Effective interactions in mixtures of silica microspheres and polystyrene
      nanoparticles.
AB  - We investigate the effect of small concentrations of highly charged nanoparticles
      on the stability of uncharged colloidal microspheres using large-scale
      simulations. Employing pair potentials that accurately represent mixtures of
      silica microspheres and polystyrene nanoparticles as studied experimentally, we
      are able to demonstrate that nanoparticle-induced stabilization can arise from a
      relatively weak van der Waals attraction between the colloids and nanoparticles.
      This demonstrates that the nanoparticle haloing mechanism for colloidal
      stabilization is of considerable generality and potentially can be applied to
      large classes of systems. The range of optimal nanoparticle concentrations can be
      tuned by controlling the attraction between colloids and nanoparticles.

PMID- 16893211
TI  - ESI-TEM imaging of surfactants and ions sorbed in Stober silica nanoparticles.
AB  - The sorption of surfactants and NaCl in silica nanosized particles creates
      unexpected spatial distributions of solutes that were evidenced by electron
      spectroscopy imaging in the transmission electron microscope (ESI/TEM). The
      spectral images show that simple ions (Na(+), Cl(-), Br(-)) are actually absorbed
      within the particles irrespective of their charges, while surfactant chains are
      adsorbed at the particle surfaces. The expected effect of the surfactants on
      particle aggregation is also observed in the micrographs. In the case of salt,
      close-packed silica particle arrays are formed at low ionic strength, but only
      coarse aggregates form at higher salt concentrations. The particles absorb both
      Na(+) and Cl(-) ions in similar amounts, from 0.5 mol L(-)(1) NaCl, but Na(+)
      ions are depleted from the particles' immediate outer vicinity, where Cl(-) ions
      are in turn accumulated. These results confirm that Stober silica nanoparticles
      are highly porous and reveal their potential usefulness as carriers of small
      molecules and ions, due to the small particle size, exceptional colloidal
      stability, and this newly found sorption behavior.

PMID- 16893210
TI  - Bias-dependent admittance in hybrid bilayer membranes.
AB  - Artificial bilayer membranes provide a platform for bioelectronic devices based
      on their structural, sensing, and transport functions. In this letter, we report
      on the impedance response of an engineered membrane with a lower leaflet of
      octadecanethiol on gold and an outer leaflet of dioleoylphosphatidylcholine with
      the monomeric channel protein gramicidin. This hybrid bilayer exhibits an
      electrical response analogous to a solid-state diode: the admittance is very low
      (<10(-)(7) Omega(-)(1) cm(-)(2)) over a wide potential range but increases
      exponentially at negative potentials.

PMID- 16893212
TI  - Self-assembly of well-defined mono and dual end-capped C(60) containing
      polyacrylic acids in aqueous solution.
AB  - Well-defined stimuli-responsive mono and dual fullerene (C(60)) end-capped
      poly(acrylic acid)s (PAA-C(60) and C(60)-PAA-C(60)) were synthesized by reacting
      C(60) with well-defined mono and dual azide end-functionalized poly(tert-butyl
      acrylate)s, followed by hydrolysis. The aggregation behaviors of these C(60) end
      capped polymers in aqueous solution were examined using potentiometric and
      conductometric titrations and static and dynamic light scattering as well as
      transmission electron microscopy (TEM). Both PAA-C(60) and C(60)-PAA-C(60) show
      pH-responsive and water-soluble properties at high pH. Both polymers self
      assemble to form large compound micelles (LCMs) in aqueous solutions. The LCMs of
      PAA-C(60) exist as "compact aggregates", whereas the LCMs of C(60)-PAA-C(60)
      possess a "core-shell" structure with a larger size and aggregation number. The
      micelles for both polymers swell upon neutralization, where the R(h) of PAA-C(60)
      micelles increases from approximately 44 to approximately 102 nm and the R(h) of
      C(60)-PAA-C(60) aggregates varies from approximately 89 to approximately 128 nm
      with increasing degree of neutralization. The lower swelling of the dual end
      capped C(60)-PAA-C(60) system is related to its higher C(60) content, which
      enhances the interpolymer chain hydrophobic association that restrains the
      swelling of micellar aggregates.

PMID- 16893213
TI  - Interactions of genistein and related isoflavones with lipid micelles.
AB  - Genistein (5,7,4'-trihydroxyisoflavone) modulates the function of several
      transmembrane ion-channel proteins by mechanisms that are unrelated to
      phosphorylation events. Daidzein (7,4'-dihydroxy-isoflavone) typically exhibits
      modest effects, whereas genistin (7-O-glucosyl-genistein) usually exhibits no
      effect on ion-channel activities. Genistein appears to modulate gramicidin A ion
      channels by alteration of bilayer mechanical properties, but the associated
      molecular interactions have not been defined. The incorporation of daidzein into
      phosphatidylcholine liposomes promotes aggregation and precipitate formation
      which is problematic for structural studies based on NMR spectroscopy. In the
      present study, daidzein was incorporated into sodium dodecyl sulfate (SDS)
      micelles to provide a stable system with no evidence of micelle aggregation. For
      this reason genistein, daidzein, genistin, and osajin (a diprenyl-genistein
      derivative) were incorporated into SDS micelles (in D(2)O) to evaluate
      differences in position and orientation within micelle structures. The (1)H NMR
      line widths, as a function of Mn(2+) concentration, indicate that genistein is
      quite mobile and buried within the hydrophobic micelle core. Daidzein and
      genistin also are mobile but exhibit average positions near the micelle/aqueous
      interface, with polar groups oriented toward the aqueous compartment. These
      results demonstrate that daidzein, with only two hydroxyl substituents, has a
      greater affinity for a polar environment than genistein with three hydroxyl
      substituents. The 5-hydroxyl group of genistein forms an intramolecular hydrogen
      bond with the 4-carbonyl group, which diminishes the molecular affinity for a
      polar matrix. These results suggest an explanation for the relative abilities of
      these compounds to increase gramicidin channel lifetimes and modulate other ion
      channel types.

PMID- 16893215
TI  - In-situ infrared study of the adsorption and oxidation of oxalic acid at single
      crystal and thin-film gold electrodes: a combined external reflection infrared
      and ATR-SEIRAS approach.
AB  - The adsorption and oxidation of oxalic acid at gold electrodes were studied by in
      situ infrared spectroscopy. External reflection experiments carried out with gold
      single-crystal electrodes were combined with internal reflection (ATR-SEIRAS)
      experiments with gold thin-film electrodes. These gold thin films, with a typical
      thickness of ca. 35 nm, were deposited on silicon substrates by argon sputtering.
      As previously reported for evaporated gold films, the voltammetric curves
      obtained in sulfuric acid solutions after electrochemical annealing show typical
      features related to the presence of wide bidimensional (111) domains with long
      range order. The in-situ infrared data collected for solutions of pH 1 confirmed
      the potential-dependent adsorption of either oxalate (Au(100)) or a mixture of
      bioxalate and oxalate (Au(111), Au(110), and gold thin films) anions in a
      bidentate configuration. The better signal-to-noise ratio associated with the
      SEIRA effect in the case of the gold thin-film electrodes allows the observation
      of the carbonyl band for adsorbed bioxalate that was not detected in the external
      reflection experiments. Besides, additional bands are observed between 2000 and
      3000 cm(-)(1) that can be tentatively related to the formation of hydrogen bonds
      between neighboring bioxalate anions. The intensities of these bands decrease
      with increasing solution pH values, disappearing for pH 3 solutions in which
      adsorbed oxalate anions are the predominant species. The analysis of the
      intensities of the nu(s)(O-C-O) and nu(C-OH) + delta(C-O-H) bands for adsorbed
      oxalate and bioxalate, respectively, suggests that the pK(a) for the surface
      equilibrium between these species is significantly lower than that for the
      solution equilibrium.

PMID- 16893214
TI  - Morphology of dry solid-supported protein monolayers dependent on the substrate
      and protein surface properties.
AB  - The morphologies of dry MrgA protein monolayers on different solid substrates
      prepared by a three-step procedure (adsorption from an incubation solution,
      rinsing to remove excess salt and protein, and drying) were investigated using
      atomic force microscopy. MrgA is a dodecameric iron-storage protein which can
      form hexagonal, two-dimensional (2D) crystalline monolayers on hydrophilic
      surfaces at low supersaturation. The formation of such two-dimensional crystals
      is heavily dependent on the pH and the salinity of the incubation solution as
      well as on the surface properties. Correlation of surface coverage with substrate
      charge, ionic strength, and pH indicates the dominance of electrostatic effects
      in adsorption, with the balance shifting between intermolecular repulsion and
      protein-substrate attraction. Close to the isoelectric point (pI) of MrgA,
      adsorption to the surface and the formation of 2D crystals are favored. By
      preparation of self-assembled monolayers of thiols with different end groups on
      template-stripped gold, the surface properties can be varied easily from high to
      very low protein affinity. The resulting patterns of the crystalline protein
      structures are novel and could be a starting point for further scientific study,
      e.g., solid-supported cocrystallization with DNA, and indeed developments with
      technological applications, such as mesostructured deposition of MrgA-caged
      nanoparticles.

PMID- 16893216
TI  - Thermodynamic investigation of n-hexane thin films adsorbed on magnesium oxide.
AB  - The thermodynamic properties of n-hexane adsorption on MgO(100) were determined
      using high-resolution volumetric adsorption isotherms in the temperature range
      195-255 K. Two distinct layering transitions are observed in the isotherms. The
      isotherms are used to calculate the two-dimensional compressibility, the
      differential enthalpy and entropy, the heat of adsorption, and the isosteric heat
      of adsorption. Neutron Diffraction is used to identify where melting of the n
      hexane monolayer takes place.

PMID- 16893217
TI  - Atomic oxygen recombination on quartz at high temperature: experiments and
      molecular dynamics simulation.
AB  - A joint experimental and theoretical approach has been developed to study oxygen
      atom recombination on a beta-quartz surface. The experimental MESOX setup has
      been applied for the direct measurement of the atomic oxygen recombination
      coefficient gamma at T(S) = 1000 K. The time evolution of the relative atomic
      oxygen concentration in the cell is described by the diffusion equation because
      the mean free path of the atoms is less than the characteristic dimension of the
      reactor. The recombination coefficient gamma is then calculated from the
      concentration profile obtained by visible spectroscopy. We get an experimental
      value of gamma = 0.008, which is a factor of about 3 less than the gamma value
      reported for O recombination over beta-cristobalite. The experimental results are
      discussed and compared with the semiclassical collision dynamics calculations
      performed on the same catalytic system aimed at determining the basic features of
      the surface catalytic activity. Agreement, both qualitative and quantitative,
      between the experimental and the theoretical recombination coefficients has been
      found that supports the Eley-Rideal recombination mechanism and gives more
      evidence of the impact that surface crystallographic variation has on catalytic
      activity. Also, several interesting aspects concerning the energetics and the
      mechanism of the surface processes involving the oxygen atoms are pointed out and
      discussed.

PMID- 16893219
TI  - Topography and surface free energy of DPPC layers deposited on a glass, mica, or
      PMMA support.
AB  - An investigation of energetic properties of 1,2-dipalmitoyl-sn-glycero-3
      phosphocholine (DPPC) layers deposited on glass, mica, and PMMA (poly(methyl
      methacrylate)) surfaces was carried out by means of contact angles measurements
      (advancing and receding) for three probe liquids (diiodomethane, water, and
      formamide). DPPC was deposited on the surfaces from water (on glass and mica) or
      methanol (on PMMA) solutions. The topography of the tested surfaces was
      determined with a help of scanning electron microscopy (SEM) and atomic force
      microscopy (AFM). Using the measured contact angles, the total apparent surface
      free energy and its components of the studied layers were determined from van Oss
      et al.'s (Lifshitz-van der Waals and acid-base components, LWAB) and contact
      angle hysteresis (CAH) approaches. It allowed us to learn about changes in the
      surface free energy of the layers (hydrophobicity/hydrophilicity) depending on
      their number and kind of support. It was found that the changes in the energy
      greatly depended on the surface properties of the substrate as well as the
      statistical number of monolayers of DPPC. However, principal changes took place
      for first three monolayers.

PMID- 16893218
TI  - Modification of surface properties of a poly(dimethylsiloxane)-based elastomer,
      RTV11, upon exposure to seawater.
AB  - Atomic force microscopy (AFM) was combined with surface analytical techniques to
      investigate the rarely addressed issue of the effect of seawater on the surface
      properties of a selected fouling-release coating, silicon elastomer RTV11
      (trademark of General Electric). The exposure of the RTV11 surface to seawater
      resulted in a modification of its morphology and mechanical properties, as
      confirmed by AFM and scanning electron microscopy (SEM). Surface modification was
      dependent on sample preparation and curing process, namely, curing agent
      concentration and relative humidity during curing. The RTV11 surface remained
      largely unaltered for samples cured under 100% relative humidity. SEM and X-ray
      photoelectron spectroscopy studies confirmed that the modified surface of RTV11
      had the same elemental composition as the unexposed surface of the elastomer and
      showed excess Ca. However, the modified surface deformed plastically under load
      and was stiffer than the original surface. No major change was found on surfaces
      exposed to nanopure water during similar times of exposure as in seawater,
      regardless of curing conditions. The rate of increase in the aggregate formation
      in seawater can be described by an exponential function, with a decay constant of
      approximately 4.99 x 10(-)(3) min(-)(1) and a pre-exponential factor of
      approximately 1.77 x 10(-)(2) microm/min.

PMID- 16893220
TI  - Loosely packed hydroxyl-terminated SAMs on gold.
AB  - We report the preparation of loosely packed hydroxyl-terminated self-assembled
      monolayers (SAMs) on gold by the adsorption of bis(11,11'
      dithioundecyl)perfluoroheptanoate and base-mediated cleavage of the fluorocarbon
      terminal group. As shown through complementary characterization methods, the
      partially fluorinated SAM exhibits a structure in which the outer surface
      contains mostly -CF(3) groups, the fluorocarbon groups are slightly canted on
      average, and the hydrocarbon chains underneath are in a fluidlike state. Upon
      cleavage of the fluorocarbon group, the hydroxyl-terminated alkyl chains relax
      into an increasingly canted, fluidlike state. The resulting monolayer packing
      exposes both methylene and hydroxyl functionalities, yielding an intermediate
      surface energy (theta(a)(H(2)O) approximately 68 degrees ). As compared to a
      densely packed hydroxyl-terminated SAM prepared from bis(11
      hydroxyundecyl)disulfide, the cleaved films are thinner because of the greater
      average chain cant and exhibit a approximately 50% higher capacitance and a
      factor of 5 lower charge-transfer resistance. The addition of THF to the
      electrolyte solution as a cosolvent intercalates into the loosely packed SAM to
      double the charge-transfer resistance and increase the capacitance by
      approximately 20% but does not affect the capacitance of the densely packed SAM.
      The loosely packed SAM is also more easily exchanged upon exposure to a solution
      of n-docosanethiol.

PMID- 16893221
TI  - Oxygen K-edge X-ray absorption fine structure studies of vacuum-deposited ice
      films.
AB  - Multilayer ice films deposited on polycrystalline Au(111) substrates at 90 and
      153 K under ultra-high-vacuum conditions are studied using O K-edge X-ray
      absorption fine structure spectroscopy in the surface-sensitive partial electron
      yield mode. Both near-edge and extended oscillatory fine structures are analyzed
      in combination with the theoretical real-space full-multiple-scattering
      simulations based on the FEFF8 code. The experimental data consistently indicate
      that the local structure of the near-surface regions in ice films at both
      substrate temperatures resembles that of high-density crystalline modifications
      of ice (e.g., ice II, ice III, or high-density amorphous ice). In addition, the
      ice films deposited at 153 K most probably contain a minor fraction of low
      density cubic ice (I(c) phase).

PMID- 16893222
TI  - Controlled strain on a double-templated textured polymer film: a new approach to
      patterned surfaces with bravais lattices and chains.
AB  - A double template-assisted fabrication method for making surface patterns with
      tunable lattice geometries on a polymer surface is reported. This technique is
      based on a locally nonuniform strain produced in a double-templated polymer film
      that has a strong modulation in thickness. It can produce all 2D primitive
      Bravais lattices as well as chains on the surface of a polymer. The lattice
      parameters are controllable with nanoprecision by varying the direction and
      amount of the applied strain.

PMID- 16893223
TI  - Adhesion of spherical polyelectrolyte brushes on mica: an in situ AFM
      investigation.
AB  - We demonstrate that the adsorption of cationic spherical polyelectrolyte brushes
      (SPB) on negatively charged mica substrates can be controlled in situ by the
      ionic strength of the suspension. The SPB used in our experiments consist of
      colloidal core particles made of polystyrene. Long cationic polyelectrolyte
      chains are grafted onto these cores that have diameters in the range of 100 nm.
      These particles are suspended in aqueous solution with a fixed ionic strength.
      Atomic force microscopy (AFM) in suspension as well as in air was used for
      surface characterization. In pure water the polymer particles exhibit a strong
      adhesion to the mica surface. AFM investigations of the dry samples show that the
      particles occupy the identical positions as they did in liquid. They were not
      removed by the capillary forces within the receding water front during the drying
      process. The strong interaction between the particles and the mica surface is
      corroborated by testing the adhesion of individual particles on the dried surface
      by means of the AFM tip: after a stepwise increase of the force applied to the
      surface by the AFM tip, the polymer particles still were not removed from the
      surface, but they were cut through and remained on the substrate. Moreover, in
      situ AFM measurements showed that particles which adsorb under liquid in a stable
      manner are easily desorbed from the surface after electrolyte is added to the
      suspension. This finding is explained by a decreasing attractive particle
      substrate interaction, and the removal of the particles from the surface is due
      to the significant reduction of the activation barrier of the particle
      desorption. All findings can be explained in terms of the counterion release
      force.

PMID- 16893224
TI  - alpha(2A)-adrenergic receptor derived peptide adsorbates: a G-protein interaction
      study.
AB  - The affinity of alpha(2A)-adrenergic receptor (alpha(2A)-AR) derived peptide
      adsorbates for the functional bovine brain G-protein is studied in the search for
      the minimum sequence recognition. Three short peptides (GPR-i2c, GPR-i3n, and GPR
      i3c) are designed to mimic the second and third intracellular loops of the
      receptor. X-ray photoelectron spectroscopy is used to study the chemical
      composition of the peptides and the binding strength to the surfaces.
      Chemisorption of the peptides to the gold substrates is observed. Infrared
      spectroscopy is used to study the characteristic absorption bands of the
      peptides. The presence of peptides on the surfaces is verified by prominent amide
      I and amide II bands. The interaction between the peptides and the G-protein is
      studied with surface plasmon resonance. It is shown that GPR-i3n has the highest
      affinity for the G-protein. Equilibrium analysis of the binding shows that the G
      protein keeps its native conformation when interacting with GPR-i3c, but during
      the interaction with GPR-i2c and GPR-i3n the conformation of G-protein is
      changed, leading to the formation of aggregates and/or multilayers.

PMID- 16893225
TI  - Adsorption behavior of rhodamine B on Rhizopus oryzae biomass.
AB  - The removal of a carcinogenic dye rhodamine B (C. I. 45170) from wastewater by
      biomass of different moulds and yeasts is described. Among all of the fungal
      species tested, the biomass of Rhizopus oryzae MTCC 262 is found to be the most
      effective. Dye adsorption reaches maximum with the biomass harvested from the
      early stationary phase of growth. The optimum temperature and pH for adsorption
      are observed to be 40 degrees C and 7.0, respectively. The adsorption rate is
      very fast initially and attains equilibrium after 5 h. The adsorption isotherm
      follows the Langmuir isotherm model satisfactorily within the studied dye
      concentration range. Of the different metabolic inhibitors tested, 2,4
      ditrophenol (DNP) and N,N'-dicyclohexylcarbodiimide (DCCD) decrease dye
      adsorption by approximately 30% suggesting the role of energy metabolism in the
      process. Spectrophotometric study indicates that the removal of rhodamine B by R.
      oryzae biomass involves an adsorption process. Scanning (SEM) and transmission
      (TEM) electron microscopic investigations have been carried out to understand the
      probable mechanism of the dye-biomass interaction.

PMID- 16893226
TI  - Ultrasound-responsive polymer-coated microbubbles that bind and protect DNA.
AB  - Ultrasound in combination with microbubbles has recently been considered by gene
      delivery scientists to be an interesting approach to enhance gene transfer into
      cells. Its low toxicity and simplicity to apply in vivo without major
      complications make this technology (sonoporation) especially attractive.
      Sonoporation of DNA has been evaluated in vivo by the injection of free plasmid
      DNA (pDNA) together with microbubbles (as used in diagnostic imaging) in the
      bloodstream. However, the in vivo gene-transfer efficiency in these experiments
      remained rather low. Both the enzymatic degradation of the injected pDNA as well
      as the low pDNA concentration in the neighborhood of sonoporated cell membranes
      may explain this low efficiency. Therefore, we developed polymer-coated
      microbubbles that can bind and protect the pDNA. Coating albumin-shelled
      microbubbles with poly(allylamine hydrochloride) (PAH) makes the surface charge
      of the microbubbles positive without drastically affecting the size distribution
      of the microbubbles, thereby not affecting the ultrasound responsiveness and
      injectability. The cationic coating allowed both to bind up to 0.1 pg of DNA per
      microbubble as well as to protect the bound DNA against nucleases. Finally, the
      PAH coating significantly increased the lifetime of the microbubbles (half-life
      approximately 7 h), making them more convenient for in vivo applications because
      more microbubbles are expected to reach the target organ. Binding and nuclease
      protection of DNA by polymer-coated diagnostic microbubbles has, to our
      knowledge, never been demonstrated. We conclude that these LbL-coated
      microbubbles might be significant in the further development of ultrasound
      mediated gene delivery.

PMID- 16893227
TI  - Modulation of calcium oxalate crystallization by linear aspartic acid-rich
      peptides.
AB  - Calcium oxalate monohydrate (COM) kidney stone formation is prevented in most
      humans by urinary crystallization inhibitors. Urinary osteopontin (OPN) is a
      prototype of the aspartic acid-rich proteins (AARP) that modulate
      biomineralization. Synthetic poly(aspartic acids) that resemble functional
      domains of AARPs provide surrogate molecules for exploring the role of AARPs in
      biomineralization. Effects of linear aspartic acid-rich peptides on COM growth
      kinetics and morphology were evaluated by the combination of constant composition
      (CC) analysis and atomic force microscopy (AFM). A spacer amino acid (either
      glycine or serine) was incorporated during synthesis after each group of 3
      aspartic acids (DDD) in the 27-mer peptide sequences. Kinetic CC studies revealed
      that the DDD peptide with serine spacers (DDDS) was more than 30 times more
      effective in inhibiting COM crystal growth than the DDD peptide with glycine
      spacers (DDDG). AFM revealed changes in morphology on (010) and (-101) COM faces
      that were generally similar to those previously described for OPN and citrate,
      respectively. At comparable peptide levels, the effects of step pinning and
      reduced growth rate caused by DDDS were remarkably greater. In CC nucleation
      studies, DDDS caused a greater prolongation of induction periods than DDDG. Thus,
      nucleation studies link changes in interfacial energy caused by peptide
      adsorption to COM to the CC growth and AFM results. These studies indicate that,
      in addition to the number of acidic residues, the contributions of other amino
      acids to the conformation of DDD peptides are also important determinants of the
      inhibition of COM nucleation and growth.

PMID- 16893228
TI  - Actin filament guidance on a chip: toward high-throughput assays and lab-on-a
      chip applications.
AB  - Biological molecular motors that are constrained so that function is effectively
      limited to predefined nanosized tracks may be used as molecular shuttles in
      nanotechnological applications. For these applications and in high-throughput
      functional assays (e.g., drug screening), it is important that the motors propel
      their cytoskeletal filaments unidirectionally along the tracks with a minimal
      number of escape events. We here analyze the requirements for achieving this for
      actin filaments that are propelled by myosin II motor fragments (heavy
      meromyosin; HMM). First, we tested the guidance of HMM-propelled actin filaments
      along chemically defined borders. Here, trimethylchlorosilane (TMCS)-derivatized
      areas with high-quality HMM function were surrounded by SiO(2) domains where HMM
      did not bind actin. Guidance along the TMCS-SiO(2) border was almost 100% for
      filament approach angles between 0 and 20 degrees but only about 10% at approach
      angles near 90 degrees . A model (Clemmens, J.; Hess, H.; Lipscomb, R.; Hanein,
      Y.; Bohringer, K. F.; Matzke, C. M.; Bachand, G. D.; Bunker, B. C.; Vogel, V.
      Langmuir 2003, 19, 10967-10974) accounted for essential aspects of the data and
      also correctly predicted a more efficient guidance of actin filaments than
      previously shown for kinesin-propelled microtubules. Despite the efficient
      guidance at low approach angles, nanosized (<700 nm wide) TMCS tracks surrounded
      by SiO(2) were not effective in guiding actin filaments. Neither was there
      complete guidance along nanosized tracks that were surrounded by topographical
      barriers (walls and roof partially covering the track) unless there was also
      chemically based selectivity between the tracks and surroundings. In the latter
      case, with dually defined tracks, there was close to 100% guidance. A combined
      experimental and theoretical analysis, using tracks of the latter type, suggested
      that a track width of less than about 200-300 nm is sufficient at a high HMM
      surface density to achieve unidirectional sliding of actin filaments. In accord
      with these results, we demonstrate the long-term trapping of actin filaments on a
      closed-loop track (width < 250 nm). The results are discussed in relation to lab
      on-a-chip applications and nanotechnology-assisted assays of actomyosin function.

PMID- 16893229
TI  - Specific and nonspecific interaction forces between Escherichia coli and silicon
      nitride, determined by poisson statistical analysis.
AB  - The nature of the physical interactions between Escherichia coli JM109 and a
      model surface (silicon nitride) was investigated in water via atomic force
      microscopy (AFM). AFM force measurements on bacteria can represent the combined
      effects of van der Waals and electrostatic forces, hydrogen bonding, steric
      interactions, and perhaps ligand-receptor type bonds. It can be difficult to
      decouple these forces into their individual components since both specific
      (chemical or short-range forces such as hydrogen bonding) and nonspecific (long
      range colloidal) forces may be present in the overall profiles. An analysis is
      presented based on the application of Poisson statistics to AFM adhesion data, to
      decouple the specific and nonspecific interactions. Comparisons with classical
      DLVO theory and a modified form of a van der Waals expression for rough surfaces
      were made in order to help explain the nature of the interactions. The only
      specific forces in the system were due to hydrogen bonding, which from the
      Poisson analysis were found to be -0.125 nN. The nonspecific forces of 0.155 nN
      represent an overall repulsive interaction. These nonspecific forces are
      comparable to the forces calculated from DLVO theory, in which electrostatic
      double layer interactions are added to van der Waals attractions calculated at
      the distance of closest approach, as long as the van der Waals model for "rough"
      spherical surfaces is used. Calculated electrostatic-double layer and van der
      Waals interactions summed to 0.116 nN. In contrast, if the classic (i.e., smooth)
      sphere-sphere model was used to predict the van der Waals forces, the sum of
      electrostatic and van der Waals forces was -7.11 nN, which appears to be a large
      overprediction. The Poisson statistical analysis of adhesion forces may be very
      useful in applications of bacterial adhesion, because it represents an easy way
      to determine the magnitude of hydrogen bonding in a given system and it allows
      the fundamental forces to be easily broken into their components.

PMID- 16893230
TI  - Selective spatial localization of actomyosin motor function by chemical surface
      patterning.
AB  - We have previously described the efficient guidance and unidirectional sliding of
      actin filaments along nanosized tracks with adsorbed heavy meromyosin (HMM;
      myosin II motor fragment). In those experiments, the tracks were functionalized
      with trimethylchlorosilane (TMCS) by chemical vapor deposition (CVD) and
      surrounded by hydrophilic areas. Here we first show, using in vitro motility
      assays on nonpatterned and micropatterned surfaces, that the quality of HMM
      function on CVD-TMCS is equivalent to that on standard nitrocellulose substrates.
      We further examine the influences of physical properties of different surfaces
      (glass, SiO(2), and TMCS) and chemical properties of the buffer solution on
      motility. With the presence of methylcellulose in the assay solution, there was
      HMM-induced actin filament sliding on both glass/SiO(2) and on TMCS, but the
      velocity was higher on TMCS. This difference in velocity increased with
      decreasing contact angles of the glass and SiO(2) surfaces in the range of 20-67
      degrees (advancing contact angles for water droplets). The corresponding contact
      angle of CVD-TMCS was 81 degrees. In the absence of methylcellulose, there was
      high-quality motility on TMCS but no motility on glass/SiO(2). This observation
      was independent of the contact angle of the glass/SiO(2) surfaces and of HMM
      incubation concentrations (30-150 microg mL(-)(1)) and ionic strengths of the
      assay solution (20-50 mM). Complete motility selectivity between TMCS and SiO(2)
      was observed for both nonpatterned and for micro- and nanopatterned surfaces.
      Spectrophotometric analysis of HMM depletion during incubation, K/EDTA ATPase
      measurements, and total internal reflection fluorescence spectroscopy of HMM
      binding showed only minor differences in HMM surface densities between TMCS and
      SiO(2)/glass. Thus, the motility contrast between the two surface chemistries
      seems to be attributable to different modes of HMM binding with the hindrance of
      actin binding on SiO(2)/glass.

PMID- 16893232
TI  - Synthesis of platinum nanoparticles by reaction of filamentous cyanobacteria with
      platinum(IV)-chloride complex.
AB  - Interaction of cyanobacteria (Plectonema boryanum UTEX 485) with aqueous
      platinum(IV)-chloride (PtCl(4) degrees ) has been investigated at 25-100 degrees
      C for up to 28 days, and 180 degrees C for 1 day. The addition of PtCl(4) degrees
      to the cyanobacteria culture initially promoted the precipitation of Pt(II)
      organic material as amorphous spherical nanoparticles (< or =0.3 microm) in
      solutions and dispersed nanoparticles within bacterial cells. The spherical
      Pt(II)-organic nanoparticles were connected into long beadlike chains by a
      continuous coating of organic material derived from the cyanobacterial cells, and
      aged to nanoparticles of crystalline platinum metal with increase in temperature
      and reaction time. The stepwise reduction for the formation of platinum
      nanoparticles in the presence of cyanobacteria was deduced to be Pt(IV) [PtCl(4)
      degrees ] --> Pt(II) [Pt(II)-organics] --> Pt(0). Spherical platinum-bearing
      nanoparticles were not present in abiotic PtCl(4) degrees experiments conducted
      under similar conditions and duration.

PMID- 16893231
TI  - Superior biolubricant from a species of red microalga.
AB  - The rheological properties of the sulfated polysaccharide of the red microalga
      Porphyridium sp., a heteropolymer with a molecular weight of 3-5 x 10(6) Da,
      indicated that this material might be an excellent candidate for lubrication
      applications: the viscosity of the polysaccharide is stable over a range of
      temperatures, pH values, and salinities. In this study, various rheological and
      lubricant properties of the polysaccharide were evaluated in comparison with
      those of a widely used biolubricant, hyaluronic acid. The viscosity of the
      Porphyridium sp. polysaccharide remained essentially unchanged in a temperature
      range of 25-70 degrees C. In tribology tests on a ball-on-flat ceramic pair, the
      values for the friction coefficient and wear rate for the pair lubricated with
      polysaccharide were remarkably lower than those for hyaluronic acid, especially
      at high loads. In a test on a steel ring/ultrahigh-molecular-weight polyethylene
      (UHMWPE) block pair, the wear tracks on the surface of the UHMWPE were more
      pronounced for hyaluronic acid than for the polysaccharide. Atomic force
      microscopy showed that the polysaccharide was effectively adsorbed onto mica
      surfaces, forming ultrathin coating layers in the nanometer range. As is required
      for biolubricant applications, the polysaccharide was not degraded by
      hyaluronidase. The stability of the Porphyridium sp. polysaccharide to heat and
      to hyaluronidase combined with its ability to reduce friction and wear indicate
      its potential as an advantageous biolubricant.

PMID- 16893233
TI  - Examination of glass transitions in CO(2)-processed, peracetylated sugars using
      sum frequency generation spectroscopy.
AB  - The present study utilizes vibrational sum frequency generation (SFG)
      spectroscopy to study changes in the surface crystallinity of various
      peracetylated sugars, a class of materials that have a high affinity for carbon
      dioxide (CO(2)). Studies of the solid-air interface of acetylated beta
      cyclodextrin (Ac-beta-CD) and sucrose octaacetate (SOA) show that diffuse
      reflectance SFG spectroscopy is sensitive to changes in crystallinity from
      processing with either heat or solvation in CO(2), due to the loss of signal
      after glassification occurs. beta-d-Glucose pentaacetate (Ac-beta-GLC) was used
      as a control for this experiment due to the fact that it does not undergo a
      crystalline phase transition, regardless of processing conditions. The
      crystalline to amorpohous transitions of these bulk materials were verified using
      differential scanning calorimetry (DSC) as a function of thermal and CO(2)
      processing. In addition, preliminary results suggest that the SFG technique is
      sensitive in detecting the degree of crystallinity at the interface as a result
      of incomplete processing and presents new opportunities for the examination and
      detection of surface crystallinity changes.

PMID- 16893234
TI  - In situ growth of ZnO nanocrystals from solid electrospun nanofiber matrixes.
AB  - Porous fiber membranes consisting of 1D assemblies of ZnO nanocrystal-supported
      poly(vinyl alcohol) (PVA) nanofibers are described. These hybrid nanofiber
      membranes were assembled by first electrospinning a ZnO precursor-containing PVA
      aqueous solution. Subsequently, the electrospun composite nanofibers were
      submerged in a basic ethanol solution. As a result, ZnO precursors in solid PVA
      matrixes were hydrolyzed to generate ZnO crystals residing on the fiber surfaces.
      Photoluminescence spectroscopy analysis demonstrated the as-hydrolyzed fiber
      membranes possess white luminescence. Furthermore, the ZnO-encapsulated PVA
      nanofibers were prepared by directly electrospinning a ZnO nanocrystal-containing
      PVA solution as the contrast of the as-hydrolyzed hybrid nanofibers. The surface
      photovoltage spectroscopy (SPS) confirmed that the as-hydrolyzed hybrid fiber
      membranes had a strong SPS response, but the directly spun fiber membranes did
      not have any SPS response. This can be attributed to the favorable structure of
      the hydrolyzed hybrid nanofibers, that is, the surface residence of ZnO permits
      ZnO crystals to make direct contact with ITO electrodes to transfer the
      photogenerated electron originating from ZnO to ITO electrodes. By contrast, the
      transfer of the photogenerated electron is limited by PVA matrixes in the
      directly spun fiber system.

PMID- 16893235
TI  - Light-scattering study of polyelectrolyte complex formation between anionic and
      cationic nanogels in an aqueous salt-free system.
AB  - We studied complex formation in an aqueous salt-free system (pH approximately 3
      and at 25 degrees C) between nanogel particles having opposite charges. Anionic
      gel (AG) and cationic gel (CG) particles consist of lightly cross-linked N
      isopropylacrylamide (NIPA) copolymers with 2-acrylamido-2-methylpropane sulfonic
      acid and with 1-vinylimidazole, respectively. The number of charges per particle
      was -4490 for AG and +20 300 for CG, as estimated from their molar masses (3.33
      MD for AG and 11.7 MD for CG) by static light scattering (SLS) and their charge
      densities (1.35 mmol/g for AG and 1.74 mmol/g for CG) by potentiometric
      titration. The complexes were formed through the addition of AG to CG and vice
      versa using a turbidimetric titration technique. At the endpoint of the
      titration, the aggregate formed was a complex based upon stoichiometric charge
      neutralization: CG(n)()(+) + xAG(m)()(-) --> CG(n)()(+) (AG(m)()(-))(x)() where x
      = (n)()/(m)(). At different stages of the titration before the endpoint, the
      resulting complexes were examined in detail using dynamic light scattering, SLS,
      and electrophoretic light scattering (ELS). The main results are summarized as
      follows: (i) When AG with a hydrodynamic radius (R(h)) of 119 nm is added to CG
      (R(h) approximately 156 nm), the (R(h)) of the complex size decreases from 156 to
      80 nm. (ii) In contrast to this (R(h)) change, the molar mass increases from 11.7
      MD to 24 MD with increasing amounts of added AG. (iii) Upon addition of CG to AG,
      the complex formed has the same size ((R(h)) approximately 80 nm) and the same
      molar mass (55 +/- 2.5 MD) until 55 +/- 5% of AG has been consumed in the
      complexation. To understand these results, we used the following two models: the
      random model (RM), in which the added AG particles uniformly bind to all of the
      CG particles in the system via a strong electrostatic attraction, and the all-or
      none model (AONM), in which part of the AG particles in the system preferably
      bind to the added CG particles to neutralize their electric charges but the other
      AG particles are uncomplexed and remain in the system. The complex formations
      upon addition of AG to CG and CG to AG were elucidated in terms of RM and AONM,
      respectively.

PMID- 16893236
TI  - Titrametric characterization of pH-induced phase transitions in functionalized
      microgels.
AB  - The chain and radial functional group distributions in carboxylic acid
      functionalized poly(N-isopropylacrylamide)-based microgels have significant
      impacts on the types of swelling responses exhibited by the microgels upon the
      application of a temperature and/or pH stimulus. Potentiometric, conductometric,
      and calorimetric titration approaches are used in this work to characterize the
      chain distributions of -COOH groups in five microgels prepared using different 
      COOH-functionalized monomers. A direct correlation is observed between the
      kinetically predicted formation of functional monomer blocks within the microgel,
      the excess Gibbs free energy of ionization, and the apparent pK(a) versus degree
      of ionization profiles generated from potentiometric titration. Isothermal
      titration calorimetry (ITC) can be used to quantify the relative number of
      functional groups present in microgels prepared with the same functional monomer
      and/or identify differences between microgels with the same bulk -COOH content
      but different chain distributions. In particular, microgels prepared with diacid
      functionalized monomers exhibit a characteristic two-step ITC profile. For
      microgels with the same bulk -COOH content, the heat of ionization measured via
      ITC increases systematically with the overall change in both the pK(a) and the
      excess Gibbs free energy for microgels prepared with monoacid-functionalized
      monomers. Diacid monomer-functionalized microgels have lower ionization
      enthalpies attributable to the break-up of hydrogen-bonded intramolecular ring
      complexes upon carboxylic acid ionization. The inferred chain functional group
      distributions can be used to understand differences in microgel swelling across
      the pH-induced phase transition.

PMID- 16893237
TI  - Gelation of native beta-lactoglobulin induced by electrostatic attractive
      interaction with xanthan gum.
AB  - The mechanism and kinetics of the electrostatic gelation of native beta
      lactoglobulin-xanthan gum mixtures in aqueous solution is reported. The total
      biopolymer concentration at which gelation was obtained was extremely low (0.1 wt
      %) compared to the usually tested concentrations for protein-polysaccharide mixed
      gels (4-12 wt %). This is, to our knowledge, the first time that oppositely
      charged proteins and polysaccharides are reported to form a gel without applying
      any treatment to denature the protein (e.g. heating, enzymatic hydrolysis) and at
      such low concentrations. Static light-scattering and viscoelastic measurements
      allowed determination of the gelation kinetics. It was found that the gelation
      process initiated following a similar path as that of an associative phase
      separation process, i.e., with the formation of primary and interpolymeric
      electrostatic complexes. However, interpolymeric complexes were able to form
      clusters and junction zones that resulted in the freeze-in of the whole structure
      at the point of gelation. The formed gel is therefore a coupled-gel, that is, a
      gel that has junction zones involving two different molecules. The structuration
      of xanthan gum, even at these low concentrations, may have played a role in the
      structuration process. Due to the electrostatic nature of the gels, there was an
      optimum pH and macromolecular ratio at which the stability of the gels was
      maximal. This was related to the existence of a stoichiometric electrical charge
      equivalence pH, where molecules carry equal but opposite charges and protein
      polysaccharide interactions are at their maximum.

PMID- 16893238
TI  - Close-packed hemispherical microlens array from two-dimensional ordered polymeric
      microspheres.
AB  - This paper describes a facile, reproducible soft-lithography-based method for
      fabricating hexagonally close-packed microlens arrays by templating the surface
      of a colloidal monolayer, which is formed by spin-casting monodisperse
      polystyrene microspheres. The relief structure of colloidal monolayers has
      successfully generated PDMS elastomers with hexagonal arrays of hemispherical air
      voids. Closely packed hemispherical microlens arrays were imprinted on
      ultraviolet-curable photopolymers which are bound on glass substrates. Atomic
      force microscopy measurements showed that each spherical hole of the PDMS molds
      is 103 nm deep and the replicated microlens is 95 nm in height with narrow size
      distribution and good reproducibility. Without a multistep engineering process,
      this method might provide a reliable route to fabricate embossed thin layers
      ranging from nanometer to micrometers by controlling the size of polymer
      microspheres over a centimeter scale area.

PMID- 16893239
TI  - Synthesis and characterization of sulfide and selenide colloidal semiconductor
      nanocrystals.
AB  - In this paper, we demonstrate the synthesis of sulfide and selenide nanocrystals
      in a water-ethanol mixed solution system. This synthetic way was based on the
      direct reactions between metal ions and S(2-)/Se. Linoleic acid was adopted to
      protect the nanocrystals from agglomeration. Without involving extreme
      experimental conditions, this less toxic synthetic route can be expected to bring
      more opportunities to nanocrystal-related research and application fields.

PMID- 16893240
TI  - Fabrications of hollow nanocubes of Cu(2)O and Cu via reductive self-assembly of
      CuO nanocrystals.
AB  - In this work, a template-free synthetic approach for generating single
      crystalline hollow nanostructures has been described. Using the small optical
      band-gap cuprous oxide Cu(2)O as a model case, we demonstrate that, instead of
      normally known spherical aggregates, primary nanocrystalline particles can first
      self-aggregate into porous organized solids with a well-defined polyhedral shape
      according to the oriented attachment mechanism, during which chemical conversion
      can also be introduced. In contrast to the spherical aggregates, where the
      nanocrystallites are randomly joined together, the Cu(2)O nanocrystallites in the
      present case are well organized, maintaining a definite geometric shape and a
      global crystal symmetry. Due to the presence of intercrystallite space, hollowing
      and chemical conversion can also be carried out in order to create central space
      and change the chemical phase of nanostructured polyhedrons. It has been revealed
      that Ostwald ripening plays a key role in the solid evacuation process. Using
      this synthetic strategy, we have successfully prepared single-crystal-like Cu(2)O
      nanocubes and polycrystalline Cu nanocubes with hollow interiors. For the first
      time, we demonstrate that nanostructured polyhedrons of functional materials with
      desired interiors can be synthesized in solution via a combination of oriented
      attachment and Ostwald ripening processes.

PMID- 16893241
TI  - Integration of self-assembled three-dimensional photonic crystals onto structured
      silicon wafers.
AB  - We report on the fabrication of high-quality opaline photonic crystals from large
      silica spheres (diameter of 890 nm), self-assembled in hydrophilic trenches of
      silicon wafers by using a novel technique coined a combination of "lifting and
      stirring". The achievements reported here comprise a spatial selectivity of opal
      crystallization without special treatment of the wafer surface, a filling of the
      trenches up to the top, leading to a spatially uniform film thickness,
      particularly an absence of cracks within the size of the trenches, and finally a
      good 3D order of the opal lattice even in trenches with a complex confined
      geometry, verified using optical measurements. The opal lattice was found to
      match the pattern precisely in width as well as depth, providing an important
      step toward applications of opals in integrated optics.

PMID- 16893243
TI  - Capillary phase transitions of linear and branched alkanes in carbon nanotubes
      from molecular simulation.
AB  - Capillary phase transitions of linear (from C(1) to C(12)) and branched (C(5)
      isomers) alkanes in single-walled carbon nanotubes have been investigated using
      the gauge-cell Monte Carlo simulation. The isotherm at a supercritical
      temperature increases monotonically with chemical potential and coincides with
      that from the traditional grand canonical Monte Carlo simulation, whereas the
      isotherm at a subcritical temperature exhibits a sigmoid van der Waals loop
      including stable, metastable, and unstable regions. Along this loop, the
      coexisting phases are determined using an Maxwell equal-area construction. A
      generic confinement effect is found that reduces the saturation chemical
      potential, lowers the critical temperature, increases the critical density, and
      shrinks the phase envelope. The effect is greater in a smaller diameter nanotube
      and is greater in a nanotube than in a nanoslit.

PMID- 16893242
TI  - Concentric-ringed structures in polymer thin films.
AB  - Novel polymer crystalline structures containing micrometer-sized concentric rings
      (or bands) were observed in thin poly(bisphenol A hexane ether) (BA-C6) films.
      The origin of the banded structures was found to be different from that of
      traditional banded spherulites in polymer systems. Analyses based on optical
      microscopy (OM) and atomic force microscopy (AFM) revealed that the banded
      structures contained alternating ridge and valley bands of polymer crystals in
      the flat-on orientation. No lamellar twisting was observed within the concentric
      ringed structures, which were developed as a result of the formation of a
      depletion zone during crystallization. The formation of a depletion zone was
      determined to be caused by the specific volume decrement between the crystal and
      the melt and by the diffusion of polymer chains to the fold surfaces of the flat
      on lamellae. The height of the ridges and the interband widths could be adjusted
      by controlling the diffusion rate. Time-of-flight secondary ion mass spectrometry
      ion images showed higher concentrations of low-molecular-weight polymer chains on
      the surfaces of the ridges than in the valleys.

PMID- 16893244
TI  - Ultrasonically induced opening of polyelectrolyte microcontainers.
AB  - The effect of ultrasonic treatments of different intensity and duration on the
      integrity and permeability of polyelectrolyte capsules was investigated both in
      poly(allylamine)/poly(styrene sulfonate) and
      Fe(3)O(4)/poly(allylamine)/poly(styrene sulfonate) polyelectrolyte capsules.
      Ultrasonic treatment of polyelectrolyte capsules induces the destruction of the
      polyelectrolyte shell and the release of the encapsulated material even at short
      (5 s) sonification times. The presence of magnetite nanoparticles significantly
      improves the efficiency of the ultrasonically stimulated release of the
      encapsulated compounds and enables magnetically controlled delivery to the
      desired site before ultrasonic treatment. Release of the encapsulated compound
      induced at ultrasonic power comparable to those of ultrasonic generators applied
      in medicine, demonstrating practical application of the ultrasonically triggered
      capsule opening in medicine.

PMID- 16893245
TI  - Duplication of photoinduced azo polymer surface-relief gratings through a soft
      lithographic approach.
AB  - In this work, a soft lithographic approach has been developed to duplicate
      photoinduced surface-relief-gratings (SRGs) of azo polymer films to generate the
      surface pattern replicas composed of different materials on various substrates.
      For this purpose, thin films of an epoxy-based azo polymer (BP-AZ-CA) were
      prepared by spin-coating, and SRGs with different structures were inscribed by
      exposing the films to interference patterns of Ar(+) laser beams at modest
      intensity (150 mW/cm(2)). Using the azo polymer films as masters, stamps of
      poly(dimethylsiloxane) (PDMS) were prepared by replica molding. The PDMS stamps
      were then used to transfer the solutions of poly(3-hexylthiophene) (P3HT),
      multiwalled carbon nanotube (MWNT), and BP-AZ-CA to different substrates by
      contact printing. Through this process, surface pattern replicas made of the
      functional materials were obtained. The pattern formation and quality depended on
      the factors such as the solution concentration, contacting time in the printing
      process, and printing pressure. Under the proper conditions, the printed patterns
      showed the same grating periods as the masters and the same relief depths as the
      stamps (replicas of the masters). This approach, showing some attractive
      characteristics such as the easiness of master preparation and the versatility of
      soft fabrication processes, can be applied to the fabrications of optical
      functional surfaces, sensors, and photonic devices.

PMID- 16893246
TI  - H-bonding-directed self-assembly of synthetic copolymers containing nucleobases:
      organization and colloidal fusion in a noncompetitive solvent.
AB  - The self-organization of random copolymers composed of a nucleobase monomer
      (either 1-(4-vinylbenzyl)thymine or 9-(4-vinylbenzyl)adenine) and dodecyl
      methacrylate (DMA) was studied in dilute chloroform solutions. The balance
      between the molar fractions of the nucleobase monomer (leading to intermolecular
      H-bonding) and DMA (soluble moiety in chloroform) in the polymer chains was found
      to be the parameter that principally influences the self-organization. DMA-rich
      copolymers are molecularly soluble in chloroform, whereas nucleobase-rich
      copolymers are insoluble in this solvent. Copolymers possessing an equimolar
      comonomer composition self-assemble into micrometer-sized particles physically
      cross-linked by intermolecular H-bonds (either thymine-thymine or adenine-adenine
      interactions, depending on the studied copolymer). Nevertheless, when mixed
      together, thymine- and adenine-based colloids fuse into thermodynamically stable
      microspheres cross linked by adenine-thymine interactions.

PMID- 16893247
TI  - Nucleation and growth characteristics of a binary low-mass organogel.
AB  - The system of bis(2-ethylhexyl) sodium sulfosuccinate and 4-chlorophenol, when
      dissolved in a nonpolar organic solvent, forms an organogel. The fibers of this
      organogel are formed through a nucleation-growth phenomenon. By reducing
      evaporation of the pregel solution, the fibers can be directed to grow with
      extremely long persistence lengths. Alignment of multiple fibers is achieved by
      inducting growth at the air-solution interface. The interplay of two zones, one
      above the critical nucleation concentration and the other below, allows
      orientation to be accomplished as fiber growth proceeds. The observations have
      implications for the use of the organogel as a template for materials synthesis.

PMID- 16893248
TI  - An interface comprising molecular wires and poly(ethylene glycol) spacer units
      self-assembled on carbon electrodes for studies of protein electrochemistry.
AB  - The characterization and application of a modified electrode interface for
      protein electrochemistry is reported. This generic interface is composed of a
      mixed monolayer of oligo(phenylethynylene) molecular wires (MWs) and
      poly(ethylene glycol) (PEG) deposited on glassy carbon electrodes by reductive
      adsorption of the respective aryl diazonium salts. Electrochemistry and scanning
      electron microscopy demonstrate that the PEG component exhibits a distinct
      decrease in nonspecific adsorption of blood serum and the proteins bovine serum
      albumin (BSA) and horseradish peroxidase (HRP) relative to a bare glassy carbon
      electrode. The ability of the MWs to facilitate efficient electron transfer
      through the PEG layer to the underlying electrode was demonstrated by covalently
      attaching ferrocenemethylamine to the end of the MWs. The calculated rate
      constant for this system was 229 +/- 30 s(-1). Covalent attachment of HRP to the
      MWs allowed direct electron transfer to the redox protein with almost ideal
      electrochemistry, indicating a specific interaction between the MW and HRP, with
      a rate constant of 13.4 +/- 2.3 s(-1). This rate constant is more rapid than
      previously reported for HRP shown to still be catalytically active. Retained
      catalytic activity of HRP was demonstrated by the enzyme responding to the
      addition of hydrogen peroxide. Similarly, by attaching myoglobin to the end of
      the MWs, a rate constant for this protein of 2 s(-1) was measured. The rigidity
      of the MWs, as well as it being longer than the PEG diluent, means this generic
      interface can be employed to investigate the electrochemistry of a wide range of
      redox proteins.

PMID- 16893249
TI  - Electrochemical and spectroelectrochemical behavior of the TCNQ(0/)(-) couple on
      a glassy carbon electrode. Layer-by-layer nucleation and growth.
AB  - On the basis of the electrochemical results obtained for thin films of 7,7,8,8-
      tetracyanoquinodimethane (TCNQ) on a glassy carbon electrode, the reduction and
      oxidation of the [TCNQ](0/)(-) couple in KCl aqueous media occurs via a mechanism
      involving layer-by-layer nucleation and growth. In situ recorded UV-visible
      spectroelectrochemical data allow two different crystal structures for the
      oxidized form of TCNQ to be discriminated.

PMID- 16893250
TI  - Sensitive single-layered oxygen-sensing systems: polypyridyl ruthenium(II)
      complexes covalently attached or deposited as langmuir-blodgett monolayer on
      glass surfaces.
AB  - Oxygen-sensing elements containing single-layered structures of luminescent
      indicators of ruthenium(II) bipyridyl complexes on glass surfaces prepared by
      covalent attachment and LB deposition are described. They are capable of
      detecting gaseous oxygen concentration by luminescence quenching of the indicator
      with reproducible and large quenching efficiencies that are comparable to the
      best quenching efficiencies obtained by other ruthenium(II) polypyridine based
      complexes immobilized in matrixes. The large quenching efficiencies for both
      films imply that the probe complexes are effectively quenched by oxygen, which is
      probably due to the thin single-layered structures with large surface-to-area
      ratio and short distance between the probe complexes and oxygen.

PMID- 16893252
TI  - Singlet oxygen--introduction.

PMID- 16893251
TI  - Submicron streptavidin patterns for protein assembly.
AB  - Micron and submicron-scale features of aldehyde functionality were fabricated in
      polymer films by photolithography to develop a platform for protein
      immobilization and assembly at a biologically relevant scale. Films containing
      the pH-reactive polymer poly(3,3'-diethoxypropyl methacrylate) and a photoacid
      generator (PAG) were patterned from 500 nm to 40 mum by exposure to 365 nm (i
      line) light. Upon PAG activation and hydrolysis of acetals, aldehyde groups
      formed. After the films were incubated with a biotinylated aldehyde reactive
      probe, the X-ray photoelectron spectroscopy results were consistent with biotin
      being attached to the surface. The background was subsequently passivated by
      flood exposure and incubation with an aminooxy-terminated poly(ethylene glycol),
      resulting in a 98% reduction in nonspecific protein adsorption. Protein
      patterning and assembly was demonstrated using streptavidin, biotinylated anthrax
      toxin receptor-1, and the protective antigen moiety of anthrax toxin and
      confirmed by fluorescence microscopy and atomic force microscopy (AFM). AFM
      demonstrated that 500 nm protein features were achieved. Because of the abundance
      of biotinylated proteins, this methodology provides a platform for protein
      immobilization and assembly for various applications in biotechnology.

PMID- 16893253
TI  - Obey or not obey? Dogs (Canis familiaris) behave differently in response to
      attentional states of their owners.
AB  - Sixteen domestic dogs (Canis familiaris) were tested in a familiar context in a
      series of 1-min trials on how well they obeyed after being told by their owner to
      lie down. Food was used in 1/3 of all trials, and during the trial the owner
      engaged in 1 of 5 activities. The dogs behaved differently depending on the
      owner's attention to them. When being watched by the owner, the dogs stayed lying
      down most often and/or for the longest time compared with when the owner read a
      book, watched TV, turned his or her back on them, or left the room. These results
      indicate that the dogs sensed the attentional state of their owners by judging
      observable behavioral cues such as eye contact and eye, head, and body
      orientation.

PMID- 16893254
TI  - Relationship between paw preference strength and noise phobia in Canis
      familiaris.
AB  - The authors investigated the relationship between degree of lateralization and
      noise phobia in 48 domestic dogs (Canis familiaris) by scoring paw preference to
      hold a food object and relating it to reactivity to the sounds of thunderstorms
      and fireworks, measured by playback and a questionnaire. The dogs without a
      significant paw preference were significantly more reactive to the sounds than
      the dogs with either a left-paw or right-paw preference. Intense reactivity,
      therefore, is associated with a weaker strength of cerebral lateralization. The
      authors note the similarity between their finding and the weaker hand preferences
      shown in humans suffering extreme levels of anxiety and suggest neural mechanisms
      that may be involved.

PMID- 16893255
TI  - When do octopuses play? Effects of repeated testing, object type, age, and food
      deprivation on object play in Octopus vulgaris.
AB  - Studying play behavior in octopuses is an important step toward understanding the
      phylogenetic origins and function of play as well as the cognitive abilities of
      invertebrates. Fourteen Octopus vulgaris (7 subadults and 7 adults) were
      presented 2 Lego objects and 2 different food items on 7 consecutive days under 2
      different levels of food deprivation. Nine subjects showed play-like behavior
      with the Lego objects. There was no significant difference in play-like behavior
      corresponding to food deprivation, age, and sex of the octopuses. The sequence of
      behaviors, from exploration to play-like behavior, had a significant influence on
      the establishment of play-like behavior, as it occurred mostly on Days 3-6 of the
      7-day experiment. The pattern of development of play-like activities after a
      period of exploration and habituation in this study agrees with the hypothesis
      that object play follows object exploration. A homologous origin of this
      behavioral trait in vertebrates and invertebrates is highly unlikely, as the last
      common ancestor might not have had the cognitive capacity to possess this trait.

PMID- 16893256
TI  - Contrasting activity patterns of two related octopus species, Octopus macropus
      and Octopus vulgaris.
AB  - Octopus macropus and Octopus vulgaris have overlapping habitats and are exposed
      to similar temporal changes. Whereas the former species is described as nocturnal
      in the field, there are conflicting reports about the activity time of the latter
      one. To compare activity patterns, the authors tested both species in the
      laboratory. Octopuses were exposed to a light-dark cycle and held under constant
      dim light for 7 days each. O. macropus showed nocturnal and light-cued activity.
      According to casual observations, O. vulgaris started out nocturnal but had
      switched to mostly diurnal when the experiment began. Individual variation of its
      activity was found. The different activity patterns of O. macropus and O.
      vulgaris might reflect their lifestyles, the latter species being more
      generalist.

PMID- 16893257
TI  - Does Octopus vulgaris have preferred arms?
AB  - Previous behavioral studies in Octopus vulgaris revealed lateralization of eye
      use. In this study, the authors expanded the scope to investigate arm
      preferences. The octopus's generalist hunting lifestyle and the structure of
      their arms suggest that these animals have no need to designate specific arms for
      specific tasks. However, octopuses also show behaviors, like exploration, in
      which only single or small groups of arms are involved. Here the authors show
      that octopuses had a strong preference for anterior arm use to reach for and
      explore objects, which points toward a task division between anterior and
      posterior arms. Four out of 8 subjects also showed a lateral bias. In addition,
      octopuses had a preference for a specific arm to reach into a T maze to retrieve
      a food reward. These findings give evidence for limb-specialization in an animal
      whose 8 arms were believed to be equipotential.

PMID- 16893258
TI  - Ordinality and inferential abilities of a grey parrot (Psittacus erithacus).
AB  - A grey parrot (Psittacus erithacus), able to label the color of the bigger or
      smaller object in a pair (I. M. Pepperberg & M. V. Brezinsky, 1991), to vocally
      quantify < or =6 item sets (including heterogeneous subsets; I. M. Pepperberg,
      1994), and separately trained to identify Arabic numerals 1-6 with the same vocal
      English labels but not to associate Arabic numbers with their relevant physical
      quantities, was shown pairs of Arabic numbers or an Arabic numeral and a set of
      objects and was asked for the color of the bigger or smaller one. The parrot's
      success showed he (a) understood number symbols as abstract representations of
      real-world collections, (b) inferred the relationship between the Arabic number
      and the quantity via stimulus equivalence, and (c) understood the ordinal
      relationship of his numbers.

PMID- 16893259
TI  - Frequency-range discriminations and absolute pitch in black-capped chickadees
      (Poecile atricapillus), mountain chickadees (Poecile gambeli), and zebra finches
      (Taeniopygia guttata).
AB  - The acoustic frequency ranges in birdsongs provide important absolute pitch cues
      for the recognition of conspecifics. Black-capped chickadees (Poecile
      atricapillus), mountain chickadees (Poecile gambeli), and zebra finches
      (Taeniopygia guttata) were trained to sort tones contiguous in frequency into 8
      ranges on the basis of associations between response to the tones in each range
      and reward. All 3 species acquired accurate frequency-range discriminations, but
      zebra finches acquired the discrimination in fewer trials and to a higher
      standard than black-capped or mountain chickadees, which did not differ
      appreciably in the discrimination. Chickadees' relatively poorer accuracy was
      traced to poorer discrimination of tones in the higher frequency ranges. During
      transfer tests, the discrimination generalized to novel tones when the training
      tones were included, but not when they were omitted.

PMID- 16893260
TI  - Developmental origins of sociality in brown-headed cowbirds (Molothrus ater).
AB  - Five variables were studied relating to the emergence of sociality in hand-reared
      cowbirds (Molothrus ater): proximity, sex assortment, reactions to adults, head
      down displays, and vocalizations. The authors were especially interested in
      female sociality because adult female birds influence male courtship, song
      content, and use through proximity, attention, and displays. The authors found
      that young female birds failed to show same-sex affiliation typical of the
      species at any point in the study. Brief introduction of adults did not affect
      social patterns. Adults used more head-down displays than juveniles, who used
      more displays with familiar peers. Directed and undirected singing emerged
      concurrently; directed singing was positively correlated with earlier hatching.
      This is the first demonstration of the need for early learning in the development
      of female sociality.

PMID- 16893262
TI  - Perception of the standard and the reversed Muller-Lyer figures in pigeons
      (Columba livia) and humans (Homo sapiens).
AB  - The authors compared perception of the standard and reversed Muller-Lyer figures
      between pigeons (Columbia livia) and humans (Homo sapiens). In Experiment 1,
      pigeons learned to classify 6 lengths of target lines into "long" and "short"
      categories by pecking 2 keys on the monitor, ignoring the 2 brackets so placed
      that they would not induce an illusion. In the test that followed, all 3 birds
      chose the "long" key more frequently for the standard Muller-Lyer figures with
      inward-pointing brackets (><) than for the figures with outward-pointing brackets
      (<>). The subjects' responses were accountable by neither overall lengths of the
      figures nor horizontal gaps between the 2 brackets. For the reversed figures,
      effects of the brackets were absent. These results suggested that the pigeons
      perceived the standard Muller-Lyer illusion but not the reversed one. Experiment
      2 confirmed that humans perceived both types of the illusion. Pigeons and humans
      may perceive the same illusory figures in different ways.

PMID- 16893261
TI  - The discrimination of temporal fine structure in call-like harmonic sounds by
      birds.
AB  - Thresholds for discriminating changes in the temporal fine structure of call
      like, harmonic sounds were measured in zebra finches (Taeniopygia guttata) and
      budgerigars (Melopsittacus undulatus). Birds could detect changes in periods as
      short as 1.225 ms at near 100% accuracy even when spectral and envelope cues were
      identical, as in time-reversed stimuli. Humans performed poorly on such stimuli,
      paralleling results from previous studies. Bird thresholds were in the range of
      those reported in neurophysiological studies of the songbird high vocal center
      (HVC) to temporally modified conspecific songs. Taken together, these results
      show that birds can hear differences in temporal fine structure in their natural
      vocalizations that go beyond human capabilities, but whether these abilities have
      communicative relevance remains to be seen.

PMID- 16893263
TI  - Immobility and supination in garter snakes (Thamnophis elegans) following
      handling by human predators.
AB  - A common response of animals to physical restraint is tonic immobility. The
      authors observed the behavior of garter snakes, Thamnophis elegans, in the field
      to determine the frequency of immobility as a response to handling. Most snakes
      fled after release, but the remainder remained immobile, sometimes on their backs
      (supination), for up to 10 min. Immobility was seen most often in pregnant
      snakes, which also were more likely than other snakes not to have moved before
      capture. Failure to move, either before or after capture, might be a consequence
      of the limited locomotory ability of gravid snakes. However, the lack of
      observations of interactions between snakes and their natural predators impedes
      researchers' understanding of the antipredator value, if any, of tonic
      immobility.

PMID- 16893264
TI  - Does direct human eye contact function as a warning cue for domestic sheep (Ovis
      aries)?
AB  - Direct eye contact may function as a warning cue during interspecific
      interactions, and human staring has been shown to influence the behavior of many
      species. The authors used an arena test to assess whether human staring altered
      the behavior of domestic sheep (Ovis aries) compared with no human eye contact.
      Sheep glanced at the staring human's face more often in the first 2 min of the
      test, indicating that they perceived a difference between the human stimuli.
      Staring also elicited more locomotor activity and urination than averted gaze.
      However, there were no differences in fear-related behaviors, suggesting that a
      staring human did not represent a greater immediate threat than a nonwatching
      human. These results imply that human staring is a warning cue for domestic
      sheep, but no more. Without further reinforcement, sheep quickly habituated to
      the warning cue.

PMID- 16893265
TI  - Appraisal process in sheep (Ovis aries): interactive effect of suddenness and
      unfamiliarity on cardiac and behavioral responses.
AB  - Appraisal theories state that an emotion results from an individual's evaluation
      of a stimulating event, which is based on a set of criteria. Each criterion
      triggers specific expressions that can be modulated by the outcome of other
      criteria. The authors analyzed the effects of the criteria of suddenness,
      unfamiliarity, and their combination on behavioral and cardiac responses in lambs
      (Ovis aries). Lambs were exposed to a visual stimulus that appeared either
      rapidly or slowly and was either unfamiliar or familiar. Suddenness induced a
      startle response and an increase in heart rate. Unfamiliarity induced an
      orientation response. The combination of suddenness and unfamiliarity enhanced
      both the heart rate increase and the behavioral orientation response. These
      results support the hypotheses of specificity and modulation of emotional
      expressions.

PMID- 16893266
TI  - What do rooks (Corvus frugilegus) understand about physical contact?
AB  - Rooks (Corvus frugilegus) do not use tools, but rapidly solve tests of physical
      cognition. The authors tested whether rooks understand the concept of physical
      contact using a task comprising a clear horizontal tube containing a stick with a
      disk attached to it and a piece of food. The rooks chose which side to pull the
      stick from to make the food accessible. Two configurations were used, with either
      the food or disk central along the tube. All 8 rooks solved the food-central
      configuration, but failed the disk-central configuration. Although they did not
      demonstrate an understanding of contact, further tests established that they
      could learn to solve these tasks provided there were salient stick cues. This
      result may arise because sticks are ecologically important for rooks.

PMID- 16893267
TI  - What do bonobos (Pan paniscus) understand about physical contact?
AB  - The present study aimed to test what bonobos (Pan paniscus) understand about
      contact. The task consisted of a clear horizontal tube containing a piece of food
      and a stick with a disk attached. The bonobos chose which side to push or pull
      the stick for the disk to contact the food and make it accessible. There were 9
      variations in tube design, which differed in the positions of the stick, disk,
      and food. All 5 bonobos passed at least 1 configuration. A recent study (A. E.
      Helme, N. S. Clayton, & N. J. Emery, 2006) found that rooks could learn only tube
      configurations that provided an asymmetrical stick cue, whereas bonobos did not
      demonstrate an understanding of contact but showed more individual variation,
      attending to the positions of the food, disk, and stick.

PMID- 16893269
TI  - Searching beneath the shelf in macaque monkeys: evidence for a gravity bias or a
      foraging bias?
AB  - The reasons underpinning search biases in 2 species of macaque monkeys (Macaca
      mulatta and Macaca arctoides) were explored over the course of 3 experiments
      requiring monkeys to search for a hidden food reward. The results reveal that
      monkeys are adept at exploiting perceptual cues to locate a food reward but are
      unable to use physical constraints such as solidity as cues to the reward's
      location. Monkeys prefer to search for a food reward beneath a solid shelf, not
      because they have an expectation that the reward should be there, but rather
      because, in the absence of usable cues, this bias emerges as a default search
      option. It is hypothesized that this bias may have its roots in a history of
      competition for food resources.

PMID- 16893268
TI  - Social learning in pig-tailed macaques (Macaca nemestrina) and adult humans (Homo
      sapiens) on a two-action artificial fruit.
AB  - An artificial fruit (AF) was used to test for social learning in pig-tailed
      macaques (Macaca nemestrina) and adult humans (Homo sapiens). A monkey
      demonstrator opened the AF, showing alternative methods to 2 groups of cage
      mates. Video films of the monkey demonstrations were presented to adult humans.
      Compared with chimpanzees and children, the macaques watched the demonstrations
      significantly less and in a much more sporadic manner. They also produced only
      very weak and transitory evidence of social learning. In contrast, the adult
      humans performed as one might expect of optimum imitators, even producing
      evidence of components of a "ratchet effect."

PMID- 16893270
TI  - Recent-onset ecstasy use: association with deviant behaviors and psychiatric
      comorbidity.
AB  - BACKGROUND: Despite increases in ecstasy (MDMA) use in the United States, little
      is known about characteristics linked with recent-onset ecstasy use, especially
      psychiatric symptoms and deviant behaviors. AIMS: To test whether individuals
      with high levels of other drug use are more likely to be recent-onset ecstasy
      users; to test whether psychiatric symptoms in adults are associated with recent
      onset ecstasy use; to explore the association between recent-onset ecstasy use
      and concomitant deviant behaviors in adolescents and adults. METHODS: Data from
      the 2001 National Survey on Drug Use and Health. FINDINGS: Recent-onset ecstasy
      use was significantly more likely to occur among adolescents and adults (18-34
      years old) who engaged in deviant behaviors during the past year as compared with
      those who did not engage in deviant behaviors during the past year. Higher levels
      of deviancy indicated a higher likelihood of being a recent-onset ecstasy user,
      and associations were strongest with nonviolent deviant behaviors such as selling
      illegal drugs and stealing. Associations between deviant behaviors and recent
      onset ecstasy use were similar in strength to associations between deviant
      behaviors and recent-onset cocaine and marijuana use, respectively. Adults who
      had past-year psychiatric symptoms (both depressive and panic symptoms) were
      twice as likely to be recent-onset ecstasy users as compared with those without
      past-year psychiatric symptoms. Greater levels of drug involvement increased the
      odds of being a recent-onset ecstasy user. CONCLUSION: Recent-onset ecstasy use
      seems to be associated with a range of other behavioral problems and may reflect
      one aspect of a larger problem behavior syndrome.

PMID- 16893271
TI  - Effect of nicotine on negative affect among more impulsive smokers.
AB  - In the present study, the authors tested the hypothesis that nicotine would
      provide greater relief from negative affect for more impulsive smokers than for
      less impulsive smokers. Euthymic adult smokers (N=70) participated in 2
      laboratory sessions, during which they underwent a negative mood induction (music
      + autobiographical memory), then smoked either a nicotinized or de-nicotinized
      cigarette. Mixed-effects regression yielded a significant Impulsivity x Condition
      (nicotinized vs. de-nicotinized) x Time interaction. Simple effects analyses
      showed that heightened impulsivity predicted greater negative affect relief after
      smoking a nicotinized cigarette but not after smoking a de-nicotinized cigarette.
      These data suggest that nicotine may be a disproportionately powerful negative
      reinforcer for highly impulsive smokers, promoting higher levels of nicotine
      dependence and inhibiting smoking cessation.

PMID- 16893272
TI  - Effects of acute and chronic nicotine on responses maintained by primary and
      conditioned reinforcers in rats.
AB  - There is growing recognition that nonnicotine factors, such as the sensory
      stimuli associated with smoking, can play a critical role in the maintenance of
      cigarette smoking. However, little is known about the effects of nicotine on
      responding maintained by these stimuli, which are assumed to be conditioned
      reinforcers. The authors used an animal model to examine the acute and chronic
      effects of nicotine on responses maintained by food and conditioned reinforcers
      (i.e., lights) and responses in the absence of programmed consequences (i.e.,
      extinction). During the acute phase, 4 male rats received 5 doses of subcutaneous
      nicotine. One dose of nicotine was then administered for a minimum of 60 days.
      Food-maintained and extinction responses did not significantly increase during
      the acute phase; however, food-maintained responses did increase during the
      chronic phase. Relative to vehicle, intermediate doses increased responses
      maintained by conditioned reinforcers during both phases. The results suggest
      that nicotine enhances responding maintained by conditioned reinforcers and
      possibly by food.

PMID- 16893274
TI  - Discounting of past outcomes.
AB  - Drug use, abuse, and addiction are common behavioral manifestations of
      impulsiveness. A useful and popular laboratory analogue of impulsiveness is
      temporal discounting. Temporal discounting refers to the reduction in the
      present, subjective value of outcomes that are temporally distant in the future.
      The extensive literature on temporal discounting indicates hyperbolic
      discounting, the magnitude effect, and the sign effect. It is possible that the
      same principles may apply to other dimensions of psychological distance,
      including past temporal distance. The purpose of the present study was to examine
      the possibility that outcomes in the past are discounted hyperbolically and at a
      similar rate to outcomes in the future. The magnitude and sign effects were also
      examined in past discounting. Indifference points of college students were
      determined from a paper-and-pencil questionnaire of future and past discounting.
      The results demonstrate that humans discount temporally distant past outcomes
      similarly to future outcomes. Discounting of the future and past are
      qualitatively and quantitatively similar; discounting of past outcomes is
      orderly, hyperbolic, and consistent with most empirical observations from studies
      of future discounting, including the magnitude and sign effects. The present
      study indicates that the discounting of past outcomes is a quantifiable
      phenomenon, and the results are similar to observations from the established
      future-discounting literature. Past discounting may be of use in the study of
      drug-dependent and other impulsive populations. Implications of a relationship
      between future and past discounting are discussed.

PMID- 16893273
TI  - Contingency management for smoking cessation in adolescent smokers.
AB  - This pilot study evaluated the use of contingency management (CM) procedures in
      combination with cognitive-behavioral therapy (CBT) for smoking cessation in
      adolescents. Twenty-eight treatment-seeking adolescent smokers participated in a
      1-month, school-based smoking cessation program and were randomly assigned to
      receive either CM with weekly CBT or CBT alone. In the CM+CBT group, biochemical
      verification of abstinence was obtained twice daily during the first 2 weeks,
      followed by daily appointments during the 3rd week and once every other day
      during the 4th week. Participants were monetarily reinforced for abstinence on an
      escalating magnitude schedule with a reset contingency. At the end of 1 week and
      1 month of treatment, abstinence verified using quantitative urine cotinine
      levels was higher in participants in the CM+CBT group (1 week: 76.7%; 1 month:
      53.0%) when compared with the CBT-alone group (1 week: 7.2%; 4 weeks: 0%). These
      preliminary results provide a strong initial signal supporting the utility of CM
      techniques for smoking cessation in adolescents and demonstrate the feasibility
      of implementing such a program in a school setting.

PMID- 16893275
TI  - Three-month stability of delay and probability discounting measures.
AB  - Psychopharmacologists are interested in delay and probability discounting because
      the tendency to discount the value of future and uncertain rewards has been
      linked with drug dependency. However, relatively little is known about the long
      term stability of discounting measures typically studied in clinical
      psychopharmacology. To evaluate the stability of discounting over a 3-month
      period, the authors compared points of subjective equality (indifference points)
      with those collected from the same subjects 3 months earlier. Seven delay
      periods, ranging from 1 week to 25 years, and 7 probability values, ranging from
      .95 to .05, were assessed in an undergraduate sample (n=22, delay discounting;
      n=18, probability discounting). The authors examined both differential stability
      (stability of individual differences) and absolute stability (stability of the
      group mean) of delay and probability discounting measures as well as their
      respective indifference points. The results demonstrate that standard delay and
      probability discounting parameters (e.g., hyperbolic k and area under the curve)
      had both differential stability and absolute stability across 3 months. Moreover,
      most indifference points in the delay and probability discounting tasks
      demonstrated both differential and absolute stability. All together, these
      results suggest that delay and probability parameters are stable enough to
      predict future behavior, such as substance abuse. Additional findings indicated
      that a hyperbolic function fitted the data better than an exponential function
      and that delay and probability discounting parameters were not significantly
      correlated.

PMID- 16893276
TI  - Alcohol dependence symptoms among college freshmen: prevalence, stability, and
      person-environment interactions.
AB  - College students are at risk for problematic alcohol use. Few studies, however,
      have examined alcohol dependence symptoms within a college sample. The current
      study assesses the prevalence, predictors, and stability of proxy Diagnostic and
      Statistical Manual of Mental Disorders (4th ed.; American Psychiatric
      Association, 1994) alcohol dependence symptoms among college freshmen.
      Participants were 3,720 freshmen taking part in a longitudinal study.
      Participants completed measures of alcohol use, fraternity and sorority
      membership, and behavioral undercontrol. Results revealed that alcohol dependence
      symptoms were prevalent and moderately stable among college freshmen. Both
      membership in a Greek organization and behavioral undercontrol predicted
      responses to our alcohol dependence proxy. In addition, Greek status interacted
      with behavioral undercontrol to predict alcohol dependence symptoms, such that
      Greek members high in behavioral undercontrol were especially vulnerable to
      symptoms of dependence.

PMID- 16893277
TI  - Alcohol-related and alcohol-free activity participation and enjoyment among
      college students: a behavioral theories of choice analysis.
AB  - College student alcohol abuse remains a significant public health problem, and
      there is a need for theory-driven and empirically based models to guide
      prevention efforts. Behavioral theories of choice assume that the decision to
      consume alcohol is influenced by the relative value of alcohol versus other
      available activities. In the present study, a sample of college student drinkers
      (N=108; 56% female, 44% male) who had previously completed a mandatory alcohol
      intervention completed a measure of alcohol-related and alcohol-free activity
      participation and enjoyment. The goals of the study were to examine the influence
      of drinking quantity and contextual variables on activity enjoyment and to
      identify enjoyable alcohol-free activities that take place on evenings when
      students might otherwise be drinking. Overall, students found alcohol-related
      activities more enjoyable than alcohol-free activities, and drinking quantity was
      positively related to enjoyment. However, alcohol-free activities such as
      watching movies, going to the theater or museums, going to bars or parties,
      hanging out with friends, eating at restaurants, and engaging in creative
      activity were generally as enjoyable as drinking. Alcohol-free activities that
      included peers or dates were more enjoyable than solitary activities. Men were
      less likely to engage in alcohol-free activities that included peers and reported
      less enjoyment related to alcohol-free activities than did women. Further
      research is required to identify procedures for increasing participation in
      alcohol-free activities and to determine whether increased alcohol-free activity
      participation results in decreased alcohol consumption.

PMID- 16893278
TI  - A randomized controlled trial of the therapeutic workplace for community
      methadone patients: a partial failure to engage.
AB  - The Therapeutic Workplace is an employment-based treatment for drug addiction
      that uses wages for work to reinforce drug abstinence. The Therapeutic Workplace
      has promoted abstinence from heroin and cocaine in treatment-resistant mothers in
      methadone treatment. This study attempted to replicate that effect in crack
      cocaine users recruited from community-based methadone programs. Participants
      were randomly assigned to a Therapeutic Workplace (n=22) or usual care control
      (n=25) group. Therapeutic Workplace participants were invited to work in the
      workplace and earn vouchers every weekday for 9 months contingent on documented
      opiate and cocaine abstinence. The two groups did not differ significantly on
      measures of cocaine or opiate use collected during study participation. Daily
      attendance and urinalysis results of the Therapeutic Workplace group were
      analyzed, and only 7 of the 22 participants initiated consistent periods of
      abstinence and workplace attendance. Two individuals gained access to the
      workplace on a few days, and 9 participants attempted to gain access to the
      workplace but never provided a drug-negative urine sample. Possible reasons for
      differences between the current study and the previous Therapeutic Workplace
      study are considered. Procedures that increase participant contact with the
      Therapeutic Workplace and its reinforcement contingencies might increase the
      likelihood of these individuals being successful in the treatment program.

PMID- 16893279
TI  - Amphetamine lowers brain stimulation reward (BSR) threshold in alcohol-preferring
      (P) and -nonpreferring (NP) rats: regulation by D-sub-1 and D-sub-2 receptors in
      the nucleus accumbens.
AB  - Differences in the mesolimbic dopamine (DA) pathway that regulates alcohol
      preference may also increase sensitivity to the reinforcing effects of other
      drugs of abuse. In the present study, the curve-shift (rate-frequency) paradigm
      was used to quantify the interaction of amphetamine with the rewarding effects of
      lateral hypothalamic brain stimulation reward (BSR) in alcohol-preferring (P) and
      -nonpreferring (NP) rats. The role of D-sub-1 and D-sub-2 DA receptors of the
      nucleus accumbens (NAcc) in mediating the reward-potentiating effects of
      amphetamine was also determined. Animals were tested with randomly administered
      amphetamine (0.25, 0.75, 1.25 mg/kg ip), DA-receptor antagonists (SCH 23390 [2.0
      microg, 5.0 microg]; eticlopride [2.0 microg, 5.0 microg]), or a combination of
      the 2 (SCH 23390 [2.0 microg, 5.0 microg] + 0.75 mg/kg amphetamine; eticlopride
      [2.0 microg, 5.0 microg] + 0.75 mg/kg amphetamine). Amphetamine produced
      comparable dose-related leftward shifts in the rate-frequency function for both P
      and NP rats, with a greater than 60% reduction observed in BSR threshold. On
      intervening days, baseline threshold was unaltered between tests and similar
      between rat lines. Unilateral infusion in the NAcc of either the D-sub-1 or D-sub
      2 receptor antagonist produced rightward shifts in the rate-frequency function of
      amphetamine, completely reversing-attenuating its reward-enhancing effects. The
      results demonstrate that amphetamine produces similar threshold-lowering effects
      in both P and NP rats and that the reward-potentiating effects of amphetamine do
      not correlate with alcohol preference under the conditions of the present study.

PMID- 16893281
TI  - Individual differences in the effect of novel environmental stimuli prior to
      amphetamine self-administration in rats (Rattus norvegicus).
AB  - These experiments determined whether individual differences in response to
      novelty subsequently predict the ability of novel stimuli, presented prior to the
      session, to decrease amphetamine self-administration. Using an inescapable
      locomotor test, the authors found that high-responder rats (Rattus norvegicus)
      showed a greater novelty-induced decrease in the acquisition of self
      administration compared with low-responder rats. This effect was dose dependent
      and generalized to sucrose-reinforced responding. Using a free-choice place
      preference test, the authors found that high-novelty-seeking rats also showed a
      greater novelty-induced decrease in the acquisition of self-administration
      compared with low-novelty- seeking rats. Regardless of individual differences,
      novelty had little effect on amphetamine self-administration during the
      maintenance phase. These results suggest that exposure to novel environmental
      stimuli may reduce acquisition of drug-taking behavior, especially among high
      novelty-seeking individuals.

PMID- 16893280
TI  - Intoxicated behavioral disinhibition and the heart rate response to alcohol.
AB  - This study examined the association between the heart rate (HR) response to
      alcohol intoxication, which is thought to reflect sensitivity to alcohol-induced
      reward and alcohol-induced behavioral disinhibition. High- and low-HR responders
      to alcohol participated in a go/no-go task, under sober and intoxicated
      conditions. Errors of commission on this task have previously been related to
      behavioral disinhibition. High-HR responders made more intoxicated commission
      errors as compared with low-HR responders. High-HR responders also reported
      increased alcohol consumption, and controlling for the latter did not alter the
      significant association between high-HR responders and increased intoxicated
      errors of commission. These results are consistent with previous findings of an
      increased risk for addictive and disinhibited behavioral propensities in
      individuals with a high-HR response to alcohol intoxication.

PMID- 16893282
TI  - Women's responses to sexual aggression: the effects of childhood trauma, alcohol,
      and prior relationship.
AB  - This study examined effects of alcohol consumption (control, moderate dose, high
      dose) and type of relationship (new, established) on women's responses to
      escalating male sexual aggression. The role of childhood trauma was also
      examined. After consuming a beverage, participants (N=220) projected themselves
      into a story portraying a social interaction with a man that depicted escalating
      sexual aggression. The story was paused 3 times to assess assertive, polite, and
      passive resistance as well as consent. Alcohol consumption increased consent and
      interacted with type of relationship to increase passive resistance and with
      level of sexual aggression to increase polite resistance. Assertive resistance
      increased and other responses decreased as the man's sexual aggression escalated.
      Childhood trauma lowered consent initially and increased passive resistance when
      rape was threatened.

PMID- 16893283
TI  - The expression of social dominance following neonatal lesions of the amygdala or
      hippocampus in rhesus monkeys (Macaca mulatta).
AB  - As part of ongoing studies on the neurobiology of socioemotional behavior in the
      nonhuman primate, the authors examined the social dominance hierarchy of juvenile
      macaque monkeys (Macaca mulatta) that received bilateral ibotenic acid lesions of
      the amygdala or the hippocampus or a sham surgical procedure at 2 weeks of age.
      The subjects were reared by their mothers with daily access to large social
      groups. Behavioral observations were conducted while monkeys were given access to
      a limited preferred food. This testing situation reliably elicited numerous
      species-typical dominance behaviors. All subjects were motivated to retrieve the
      food when tested individually. However, when a group of 6 monkeys was given
      access to only 1 container of the preferred food, the amygdala-lesioned monkeys
      had less frequent initial access to the food, had longer latencies to obtain the
      food, and demonstrated fewer species-typical aggressive behaviors. They were thus
      lower ranking on all indices of social dominance. The authors discuss these
      findings in relation to the role of the amygdala in the establishment of social
      rank and the regulation of aggression and fear.

PMID- 16893285
TI  - The role of voluntary exercise in enriched rearing: a behavioral analysis.
AB  - The effects of postweaning enriched rearing and home cage voluntary wheel-running
      exercise in adulthood were contrasted on a comprehensive battery of tests
      designed to assess mnemonic, attentional, emotional, and motor functions. In a 2
      x 2 factorial design, female C57BL/6 mice were housed in groups in either
      standard or enriched cages, which were equipped with either a running or a locked
      wheel. They were maintained in the corresponding housing conditions for 2 months
      postweaning prior to, and throughout, testing. Enriched rearing was associated
      with anxiogenesis, hypolocomotor activity, enhanced motor skills, retarded
      extinction of conditioned responding, and improved water maze performance.
      Exercise as such enhanced motor coordination and facilitated extinction of
      contextual conditioning. Evidence for an interaction between enrichment and
      exercise was apparent in the open field test, conditioned freezing to a tone
      stimulus, prepulse inhibition, and acquisition of water maze reference memory.
      Hence, care should be taken to control for the unique contribution of wheel
      running exercise when it is included as an integral component of the enrichment
      procedure.

PMID- 16893284
TI  - The impact of selective amygdala, orbital frontal cortex, or hippocampal
      formation lesions on established social relationships in rhesus monkeys (Macaca
      mulatta).
AB  - Social dominance, personality ratings, and frequency, duration, and timing of
      social behaviors were measured pre- and postsurgically in 6 groups of rhesus
      monkeys (Macaca mulatta), each consisting of 1 sham-operated control and 1 monkey
      each with a selective amygdala, hippocampal, or orbital frontal cortex lesion.
      Unlike previous reports, none of the operated groups showed changes in social
      dominance postsurgery, although changes in other measures varied by lesion site.
      Although sham-operated monkeys displayed heightened avoidant, anxious, and
      aggressive behaviors, those with hippocampal lesions also showed increased
      exploration and excitability, along with reduced responses to affiliative
      signals. Amygdala lesions yielded several personality changes that precluded
      positive social interactions (increased exploration and excitability, decreased
      affiliation and popularity) and altered responses to threatening social signals.
      By contrast, monkeys with orbital frontal lesions were involved in more
      aggressive interactions and responded differently to both affiliative and
      threatening signals. Although several findings differ from earlier nonhuman
      primate studies, they are largely in agreement with human data and emphasize the
      context-specific nature of social behavior studies. Interpretation of results in
      relation to cognitive processes mediated by each structure is discussed.

PMID- 16893286
TI  - Comprehensive computerized assessment of cognitive sequelae of a complete 12-16
      hour fast.
AB  - Food deprivation has been shown to deleteriously affect human cognition, but
      findings are equivocal, and few studies have examined several cognitive domains.
      In this study, the authors used computerized testing to describe the profile of
      shifts in cognition attributable to short-term religious fasting. Multiple
      cognitive domains were evaluated at midday and late afternoon following complete
      abstention from eating and drinking beginning at midnight. Cross-domain, fasting
      related deficits were found for tasks requiring perception of spatial relations.
      Fasting-related information processing deficits were found for response time but
      not accuracy for test levels of intermediate difficulty. Time-of-day effects
      often reflected poorer afternoon performance. These findings provide a detailed
      profile of cognitive consequences of food deprivation, affected by time of day,
      task demands, and type of outcome.

PMID- 16893287
TI  - Contemplation of moral dilemmas eliminates sex differences on the Iowa gambling
      task.
AB  - Men outperform women on the Iowa Gambling Task (IGT; A. Bechara, H. Damasio, D.
      Tranel, & A. R. Damasio, 1997). In this study, the authors show that sex
      differences are not due to differences in general emotional arousal or the
      abilities to calculate or reverse responses. Imaging studies have shown that,
      during the IGT, men increase activity in the right dorsolateral prefrontal cortex
      (PFC) and lateral orbital PFC, whereas women increase activity in the left medial
      orbital PFC. Deliberation of personal moral (PM) dilemmas also increases activity
      in medial and lateral dorsal PFC, whereas deliberation of moral impersonal (MI)
      dilemmas increases activity in lateral dorsal PFC. In the present study, men and
      women performed the IGT during PM, MI, or control deliberations. Deliberation of
      only PM dilemmas increased women's IGT performance to the level of men.

PMID- 16893288
TI  - Strain-dependent recovery of spontaneous hindlimb movement in spinal cord
      transected mice (CD1, C57BL/6, BALB/c).
AB  - Reorganization and plasticity after spinal cord injury have been recently shown
      to take place in sublesional neuronal networks, but the possibility of strain
      dependent changes at that level has never been explored. The authors studied the
      spontaneous return of hindlimb movement in low-thoracic spinal cord transected
      (Tx) mice from 3 commonly used strains. Without intervention, most CD1, C57BL/6,
      and BALB/c mice displayed some hindlimb movement recovery after Tx. Although all
      assessment methods unanimously reported that CD1 displayed higher recovery levels
      than did the C57BL/6 and BALB/c, higher scores were generally found with the
      Antri-Orsal-Barthe (M. Antri, D. Orsal, & J. Y. Barthe, 2002) and the Average
      Combined Score (P. A. Guertin, 2005a) methods. Such spontaneous recovery in low
      thoracic Tx mice is likely the result of neuronal plasticity at the lumbosacral
      spinal cord level, suggesting that these sublesional changes are strain
      dependent.

PMID- 16893289
TI  - Spared feature-structure discrimination but diminished salience of environmental
      geometry in hippocampal-lesioned homing pigeons (Columba livia).
AB  - Homing pigeons (Columba livia) were trained to locate a goal in one corner of a
      rectangular arena by either its shape (geometry) or the left-right configuration
      of colored features located in each corner (feature structure). Control and
      hippocampal-lesioned pigeons learned at a similar rate, but the control birds
      made proportionally more geometric errors during acquisition. On conflict probe
      trials, the control birds preferred geometrically correct corners, whereas the
      hippocampal-lesioned birds displayed a greater preference for the correct corner
      defined by feature structure. On geometry-only probe trials, both groups
      demonstrated an ability to identify the goal location. Hippocampal lesions do not
      interfere with goal recognition by the feature structure of local cues but
      diminish the salience of arena shape.

PMID- 16893291
TI  - Lesions of the dorsal hippocampus or parietal cortex differentially affect
      spatial information processing.
AB  - The present experiments used 2 versions of a modified Hebb-Williams maze to test
      the role of the dorsal hippocampus (dHip) and parietal cortex (PC) in processing
      allocentric and egocentric space during acquisition and retention. Bilateral
      lesions were made to either the dHip or PC before maze testing (acquisition) or
      after maze testing (retention). The results indicate that lesions of the dHip
      impair allocentric maze acquisition, whereas lesions of the PC impair egocentric
      maze acquisition. During retention, lesions of the PC produced a significant
      impairment on both maze versions, whereas lesions of the dHip produced short
      lived, transient impairments on both maze versions. These results suggest that
      during acquisition, the hippocampus and PC process spatial information in
      parallel; however, long-term retention of spatial information requires the PC
      with the dHIP as necessary for retrieval and/or access but not necessarily
      storage.

PMID- 16893292
TI  - The expression of fear-potentiated startle during development: integration of
      learning and response systems.
AB  - Relative to freezing, fear-potentiated startle (FPS) is developmentally delayed.
      Rats trained on Postnatal Day (PD) 18 expressed conditioned stimulus learning on
      PD 19 in freezing but not in FPS, whereas rats trained on PD 24 and tested on PD
      25 expressed both freezing and FPS (Experiment 1). According to a neural
      maturation hypothesis, this delay results from functional immaturity of pathways
      mediating FPS. When rats were trained on PD 18, neither delaying the FPS test,
      allowing FPS pathways to develop, nor administrating the "reminder" treatment,
      the expression of FPS was promoted (Experiments 1, 2, and 2A). PD 18 learning was
      expressed in FPS on PD 25 when nontarget conditioned stimulus-unconditioned
      stimulus training occurred prior to the test, and this effect was modality
      dependent (Experiments 3 and 4). The authors conclude that engaging mechanisms of
      associative encoding when FPS pathways are functional is a critical condition for
      integrating learning and FPS response systems in development.

PMID- 16893290
TI  - Chronic stress impairs spatial memory and motivation for reward without
      disrupting motor ability and motivation to explore.
AB  - This study uses an operant, behavioral model to assess the daily changes in the
      decay rate of short-term memory, motivation, and motor ability in rats exposed to
      chronic restraint. Restraint decreased reward-related motivation by 50% without
      altering memory decay rate or motor ability. Moreover, chronic restraint impaired
      hippocampal-dependent spatial memory on the Y maze (4-hr delay) and produced CA3
      dendritic retraction without altering hippocampal-independent maze navigation (1
      min delay) or locomotion. Thus, mechanisms underlying motivation for food reward
      differ from those underlying Y maze exploration, and neurobiological substrates
      of spatial memory, such as the hippocampus, differ from those that underlie short
      term memory. Chronic restraint produces functional, neuromorphological, and
      physiological alterations that parallel symptoms of depression in humans.

PMID- 16893293
TI  - Immediate shock deficit in fear conditioning: effects of shock manipulations.
AB  - Pavlovian contextual fear conditioning occurs when an aversive unconditional
      stimulus (US), such as a footshock, is presented to a rat shortly after it is
      placed in an experimental context. Contextual fear conditioning does not occur
      when the shock is presented immediately upon placement of the rat in the novel
      chamber. In the present study, the authors report that increasing either the
      number of immediate shock sessions (Experiment 1) or the immediate shock duration
      (Experiment 2) did not reverse this deficit. However, immediate shock seems to
      sensitize subsequent context conditioning (Experiment 3). These findings suggest
      that the associative deficit produced by immediate shock is not related to the
      rat's ability to process the footshock US.

PMID- 16893294
TI  - Medial auditory thalamic nuclei are necessary for eyeblink conditioning.
AB  - The auditory conditioned stimulus (CS) pathway that is necessary for delay
      eyeblink conditioning was investigated with induced lesions of the medial
      auditory thalamus contralateral to the trained eye in rats. Rats were given
      unilateral lesions of the medial auditory thalamus or a control surgery followed
      by twenty 100-trial sessions of delay eyeblink conditioning with a tone CS and
      then five sessions of delay conditioning with a light CS. Rats that had complete
      lesions of the contralateral medial auditory thalamic nuclei, including the
      medial division of the medial geniculate, suprageniculate, and posterior
      intralaminar nucleus, showed a severe deficit in conditioning with the tone CS.
      Rats with complete lesions also showed no cross-modal facilitation (savings) when
      switched to the light CS. The medial auditory thalamic nuclei may modulate
      activity in a short-latency auditory CS pathway or serve as part of a longer
      latency auditory CS pathway that is necessary for eyeblink conditioning.

PMID- 16893295
TI  - Prolonged rewarding stimulation of the rat medial forebrain bundle: neurochemical
      and behavioral consequences.
AB  - Extracellular dopamine levels were measured in the rat nucleus accumbens by means
      of in vivo microdialysis. Delivery of rewarding medial forebrain bundle
      stimulation at a low rate (5 trains/min) produced a sustained elevation of
      dopamine levels, regardless of whether train onset was predictable. When the rate
      of train delivery was increased to 40 trains/min, dopamine levels rose rapidly
      during the first 40 min but then declined toward the baseline range. The
      rewarding impact of the stimulation was reduced following prior delivery of
      stimulation at the high, but not the low, rate. These results support the idea
      that dopamine tone plays an enabling role in brain stimulation reward and is
      elevated similarly by predictable and unpredictable stimulation.

PMID- 16893297
TI  - Sex differences in electrophysiological and behavioral responses to NaCl taste.
AB  - We tested the hypothesis that sex differences in preference for NaCl are
      attributable to estrogen-mediated alterations in gustatory processing.
      Electrophysiological responses of the chorda tympani nerve to NaCl were blunted
      by estrogen treatment in ovariectomized female rats, suggesting that females are
      less sensitive to concentrated NaCl solutions during high estrogen conditions. In
      contrast, after a taste aversion was conditioned to 150-mM NaCl, estrogen- and
      oil-treated ovariectomized rats generalized the aversion to a lower concentration
      of NaCl than did males, suggesting that females are more sensitive to the taste
      of dilute NaCl solutions regardless of estrogen. Thus, sex differences in NaCl
      preferences may be attributable to differences in NaCl taste processing that
      involve both acute and developmental effects of estrogen.

PMID- 16893296
TI  - Estradiol's effects on learning and neuronal morphology vary with route of
      administration.
AB  - Estrogen's effects on performance and neuronal morphology are variable, and the
      reasons for this variability are not yet understood. In this study, the authors
      compared the effects of 2 delivery routes of 17 beta-estradiol on spatial
      learning and dendritic spine densities in young ovariectomized rats; estradiol
      was administered by implanted capsules or by daily oral gavage. Estradiol
      treatment via capsules improved performance in the radial-arm water maze and
      increased spine densities on dendrites of CA1 pyramidal neurons in the
      hippocampal formation. In contrast, daily oral administration of estradiol did
      not affect either measure. These data demonstrate that estradiol delivery is a
      critical variable in animal studies and that clinical studies comparing the
      effects of different estradiol treatment routes on cognition are warranted.

PMID- 16893298
TI  - Effect of vomeronasal organ removal from male mice on their preference for and
      neural Fos responses to female urinary odors.
AB  - Four experiments were conducted to determine whether vomeronasal organ (VNO)
      inputs in male mice mediate the rewarding properties of estrous female urinary
      odors. Sexually naive male mice with either an intact (VNOi) or lesioned (VNOx)
      VNO preferred to investigate female urine over water in Y-maze tests.
      Subsequently, VNOi males ran significantly more quickly and remained in nasal
      contact longer with estrous female urine than with male urine, whereas VNOx males
      investigated these odors equally. In home-cage habituation-dishabituation tests,
      VNOi males also investigated female urine significantly longer than did VNOx
      males, although both groups investigated female urine longer than other non-body
      odors. Finally, female urinary odors induced Fos in the nucleus accumbens core of
      VNOi males but not of VNOx males. Our results suggest that female urinary odors
      retain some incentive value in VNOx males. However, once direct nasal contact is
      made with female urine, VNO inputs further activate forebrain mechanisms that
      amplify the reward salience of this stimulus for the male mouse.

PMID- 16893299
TI  - Effects of neuropeptide Y on feeding microstructure: dissociation of appetitive
      and consummatory actions.
AB  - The effects of intracerebroventricular application of Neuropeptide Y (NPY) on
      licking microstructure for sucrose, saccharin, and water solutions were
      evaluated. In Experiment 1, NPY increased meal size for three sucrose
      concentrations (0.03 M, 0.3 M, and 1.0 M) by increasing licking burst number but
      not size and by extending meals more than four-fold in duration with a slow,
      sustained rate of ingestion in late phases of the meal. Results are consistent
      with the interpretation that NPY suppressed inhibitory postingestive feedback.
      Experiment 2 supported this conclusion. NPY significantly increased the number of
      meals initiated for water, 0.1% saccharin, and 1.0 M sucrose solutions, but meal
      size was only increased for 1.0 M sucrose. Therefore, NPY also increased
      appetitive feeding behaviors, but its consummatory effects were limited to
      caloric solutions. The results are discussed with regard to their potential to
      explain current discrepancies in the literature.

PMID- 16893300
TI  - Forebrain structures specifically activated by conditioned taste aversion.
AB  - This study investigates which forebrain structures show Fos protein expression
      during conditioned taste aversion (CTA) acquisition and whether Fos expression
      depends on the aversion strength. A novel taste paired with an intraperitoneal
      injection of a low dose of the malaise-inducing agent lithium chloride (LiCl)
      induced a weak CTA, whereas associating this novel taste with a high dose of LiCl
      induced a strong CTA. Increasing the strength of the gastric malaise alone
      enhanced Fos expression in central, basal, and lateral amygdala nuclei and
      decreased Fos expression in the nucleus accumbens core. Taste-malaise association
      induced specific Fos activation in the insular cortex (with both the low and the
      high doses of LiCl) and the nucleus accumbens shell (with the high LiCl dose
      only). No significant variation of Fos expression was measured in the perirhinal
      cortex. Several forebrain areas may be sites of taste-malaise convergence during
      CTA acquisition depending on the strength of the aversion.

PMID- 16893301
TI  - Effect of conditioning method and testing method on strength of lithium-induced
      taste aversion learning.
AB  - Here the authors evaluated the effect of the method of conditioning (bottle or
      intraoral [IO] infusion) on the strength of a flavor-drug association when
      measured in a standard 1-bottle consumption test or when measured by IO infusion
      in a taste reactivity test. When tested with the bottle test in Experiment 1,
      rats conditioned by bottle displayed stronger taste avoidance than those
      conditioned by IO infusion. When tested for rejection reactions with the taste
      reactivity test in Experiment 2, rats conditioned by infusion displayed a
      stronger aversion than did rats conditioned by bottle. The results suggest that
      when the contextual cues of conditioning are similar at conditioning and testing,
      a stronger association is evident regardless of the individual specifics of each
      method. These results may shed light on recent reports that different neural
      mechanisms are involved in conditioning by active consumption and passive
      infusion.

PMID- 16893302
TI  - Perirhinal cortex lesions impair simultaneous but not serial feature-positive
      discrimination learning.
AB  - The role of the perirhinal cortex in discriminative eyeblink conditioning was
      examined by means of feature-positive discrimination procedures with simultaneous
      (A-/XA+) and serial (A-/X-->A+) stimulus compounds. Lesions of the perirhinal
      cortex severely impaired acquisition of simultaneous feature-positive
      discrimination but produced no impairment in serial feature-positive
      discrimination. The results suggest that the perirhinal cortex plays a role in
      discriminative eyeblink conditioning by resolving ambiguity in discriminations
      with overlapping stimulus elements.

PMID- 16893303
TI  - The effects of temporary inactivation of the orbital cortex in the signal
      attenuation rat model of obsessive compulsive disorder.
AB  - Rats undergoing extinction of lever pressing after an external feedback for this
      behavior was attenuated by extinguishing its Pavlovian association with the
      reward (signal attenuation) exhibit compulsive lever pressing. The present study
      tested the effects of temporary inactivation of the orbital cortex in rats
      undergoing extinction of lever pressing that was or was not preceded by signal
      attenuation (post-training signal attenuation and regular extinction,
      respectively). Orbital inactivation led to a nonspecific decrease in lever
      pressing in rats undergoing post-training signal attenuation and to the emergence
      of compulsive-like behavior in rats undergoing regular extinction. These results
      suggest that orbital inactivation and extinguishing a Pavlovian stimulus
      reinforcer contingency have a similar effect on lever pressing and are in line
      with previous findings implicating the orbital cortex in mediating the effects of
      previously acquired stimulus-reinforcer associations on operant behavior.

PMID- 16893304
TI  - Executive functions in the heterozygous reeler mouse model of schizophrenia.
AB  - Deficits in working memory and executive functions are now considered among the
      most reliable endophenotypes for schizophrenia. To determine whether cognitive
      deficits exist in mouse models of the disease, the authors trained heterozygous
      reeler (+/rl) mice on a series of visual discriminations similar to those used to
      test executive abilities in primates. These mice resemble schizophrenia patients
      in that both have reduced levels of reelin protein and altered gamma aminobutyric
      acid neurotransmission in the prefrontal cortex. The +/rl mice showed a selective
      deficit in reversal learning, with a pattern of errors that suggested impaired
      visual attention rather than a deficiency in perseveration and inhibitory
      control. These results show that cognitive dysfunction may serve as a useful
      biomarker in mouse models of neuropsychiatric disease.

PMID- 16893305
TI  - The amygdala and development of social cognition: theoretical comment on Bauman,
      Toscano, Mason, Lavenex, and Amaral (2006).
AB  - Nonhuman primate studies, using selective amygdala lesions that spare cortical
      areas and fibers of passage, have helped to clarify the amygdala's specific
      contribution to social and emotional behavior. M. D. Bauman, J. E. Toscano, W. A.
      Mason, P. Lavenex, and D. G. Amaral (2006) reported that macaque monkeys (Macaca
      mulatta) with neonatal neurotoxic amygdala lesions displayed lower rank in social
      dominance status, reduced aggressive gestures, and enhanced fearful reactions to
      social cues compared with normal controls and those with neonatal hippocampal
      lesions when tested as juveniles in a group of peers. These results are discussed
      in light of a recent study (C. J. Machado & J. Bachevalier, 2006) showing that
      the same selective amygdala damage in adolescent monkeys did not alter
      presurgical social dominance status. This variability in behavioral changes after
      selective amygdala lesions underscores the significant interplay between timing
      of the lesion, genetic traits, and environmental factors and suggests that the
      amygdala is not the generator of specific emotional responses, but acts as a
      modulator to ensure that emotional responses are appropriate to the external
      stimuli and social context.

PMID- 16893306
TI  - Dopamine and reward: comment on Hernandez et al. (2006).
AB  - Many lines of evidence suggest that the dopaminergic projection from the midbrain
      tegmentum to the forebrain must play a critical role in mediating the behavioral
      effects of natural and artificial rewards, with brain stimulation reward and
      addictive drugs included in the latter category. However, a closer look reveals
      many incongruities. The work of G. Hernandez et al. (2006) resolves several
      puzzles. It implies that the dopaminergic projection does not carry the signal
      that encodes the magnitude of a brain stimulation reward. It suggests that the
      elevation in the tonic levels of dopamine consequent on brain stimulation reward
      modulates the registration of the magnitude of the reward. This reconciles the
      psychophysical evidence with the pharmacological, electrophysiological, and
      anatomical evidence. However, some serious puzzles do remain.

PMID- 16893307
TI  - Socioeconomic determinants of planned methadone treatment.
AB  - OBJECTIVES: To examine socioeconomic characteristics associated with planned
      methadone maintenance treatment (MMT). METHODS: We performed multiple logistic
      regressions using data from the 1998 Treatment Episode Data Set, which tracks
      admissions for substance abuse treatment. RESULTS: MMT was more prevalent among
      heroin users than nonheroin users. Among heroin users, females, Hispanics,
      Southerners, the employed, and those who are not homeless or in jail are more
      likely to be planned to receive MMT. Among nonheroin users, females were less
      likely to be planned for MMT. CONCLUSIONS: Greater effort may be necessary to
      extend MMT to vulnerable populations.

PMID- 16893308
TI  - Women who put condoms on male partners: correlates of condom application.
AB  - OBJECTIVE: To identify correlates of women applying condoms. METHODS: Cross
      sectional survey of 533 sexually-active women; questionnaire. RESULTS: Of the
      condom users (n = 322), 31.7% reported applying condoms at least once--an average
      on 59.7% of the occasions. Compared to nonappliers, appliers had more positive
      affect toward sexually related situations (erotophilia, P = .004) and a higher
      frequency of sex (P = .003). Condom users, compared to nonusers, were
      significantly younger (P = .001), were less likely to be in sexually exclusive
      relationships (P = .001) or married (P = .01), and reported more partners in the
      past 3 months (P = .001). CONCLUSIONS: Condom-applying women may have more
      positive attitudes toward sexuality and engage in a higher frequency of sexual
      activity.

PMID- 16893309
TI  - Consent form return rates for third-grade urban elementary students.
AB  - OBJECTIVE: To maximize active parent consent form return rates for third-grade
      minority, urban students enrolled in predominantly low-income elementary schools
      in Chicago, Ill. METHODS: Research staff used a class incentive and class visits
      to retrieve consent forms from students. RESULTS: Of the 811 third-grade
      students, 98% returned a form and 79% (n = 627) of those students' parents
      provided an affirmative response. Return rates did not vary by students'
      ethnicity or by the schools' demographic variables. CONCLUSION: Incentives and
      class visits can yield a high return rate of active parent consent forms for
      third-grade minority, urban, low-income students.

PMID- 16893310
TI  - Aberrant drug-taking behaviors and headache: patient versus physician report.
AB  - OBJECTIVE: To explore prevalence of aberrant medication-taking behaviors (AMTB)
      among headache patients and treating physician's awareness of such behaviors.
      METHODS: Fifty patientphysician dyads were surveyed on patients' AMTB. RESULTS:
      The most frequently endorsed behaviors by patients and physicians, respectively,
      were going to the ER for pain medication (n = 19) and continuing to take pain
      medication despite minimal relief (n = 23). For the majority of AMTB, phi
      coefficients indicating level of patient-physician agreement were equal to
      chance. CONCLUSIONS: Headache patients perform a wide range of AMTB. Low rates of
      patient-physician agreement indicate that physicians possess limited knowledge of
      patients' AMTB.

PMID- 16893311
TI  - The effect of health communications on a statewide West Nile Virus public health
      education campaign.
AB  - OBJECTIVES: To determine knowledge, behavior, and attitude among Kansas residents
      exposed to a statewide West Nile Virus health education campaign. METHODS:
      Telephone survey employing random selection of urban and rural counties and
      telephone numbers. RESULTS: Knowledge was widespread, preventive behaviors less
      so. TV, newspapers, and word-of-mouth were most frequently cited sources of
      information. A small percentage of individuals received information from health
      professionals. CONCLUSIONS: Recommendations are made for designing and
      implementing future campaigns, including taking into account target population
      demographics, populations at highest risk, and channels of communication. Greater
      use of the Internet, word of mouth, and newspapers appear most promising.

PMID- 16893312
TI  - Shared health behaviors among older Mexican American spouses.
AB  - OBJECTIVE: To assess the association of health behaviors among husbands and
      wives. METHODS: Cohort study of 553 Mexican American couples aged 65 years or
      older from the Hispanic Established Populations for the Epidemiologic Studies of
      the Elderly (H-EPESE). Multivariate regression analyses test the association of
      body mass index, smoking, and alcohol consumption among husbands and wives.
      RESULTS: Body mass index is positively associated among couples. Risk of smoking
      or drinking was higher if the partner had ever smoked or drank alcohol.
      CONCLUSION: Health behaviors are associated among older Mexican American couples.
      Intervention efforts should be directed at both spouses.

PMID- 16893313
TI  - Pediatricians' practices regarding smoking cessation among parents of their
      patients.
AB  - OBJECTIVE: To assess pediatricians' use of the 5A's for smoking cessation among
      the parents of their patients. METHODS: A random sample of Ohio pediatricians
      (n=153) completed a mail survey on smoking cessation activities. RESULTS: Most
      pediatricians (80%) regularly asked their patients' parents about their smoking
      status. The majority "always" or "usually" implemented 2 of the 5 steps of the
      5A's. Respondents perceived using the 5A's would result in fewer parents smoking
      but were less confident they could implement all of the 5A's. CONCLUSIONS:
      Pediatricians need more training to better prepare them to assist parents in
      quitting smoking.

PMID- 16893314
TI  - Modeling dimensions of choice in accepting the smallpox vaccine.
AB  - OBJECTIVE: To model the dimensionality of understanding refusal to be vaccinated
      against smallpox. METHOD: The Smallpox Vaccination Choice Questionnaire was
      administered to a convenience sample of students. Through a series of factor
      analyses, responses were subjected to a statistical evaluation of the underlying
      factor structure of potential influences on choice. RESULTS: The analyses suggest
      5 dimensions: knowledge, perceptions of risk and worry, psychological distress,
      general beliefs about vaccines, and age. CONCLUSION: This model will be used to
      help identify targets of intervention to increase acceptance of the vaccine and
      satisfaction with choice.

PMID- 16893315
TI  - Severe injury and the need for improved safety training among working teens.
AB  - OBJECTIVES: To evaluate work characteristics and safety training among teenagers
      with severe work-related injuries. METHODS: A questionnaire was administered to
      6810 high school Wisconsin students in May 2003. RESULTS: Fifteen percent of
      working teens reported being injured at work. Variables associated with severe
      injury included having a near-miss incident at work (AOR = 8.72, 95%CI = 5.51
      13), working after 11:00 PM (AOR = 4.21, 95%CI=2.08-8.53), and being asked to do
      something dangerous (AOR = 2.59, 95%CI = 1.53-4.39). CONCLUSIONS: Prohibiting
      teens from working long and late hours, improved safety training, and increased
      communication between teens and their coworkers and supervisors may help reduce
      the occurrence of injury.

PMID- 16893316
TI  - Relation of parent-teen agreement on restrictions to teen risky driving over 9
      months.
AB  - OBJECTIVES: To determine the relations among parent-teen discordance for
      restrictions on driving conditions, driving rules, and consequences for rule
      violations at licensure and subsequent risky teen driving. METHODS: Parents and
      teens completed telephone interviews at 1, 4, and 9 months after teens became
      licensed. RESULTS: At each time interval, the degree of disagreement with parent
      restrictions on driving conditions was positively associated with teen risky
      driving. CONCLUSIONS: These results demonstrate a positive association between
      parent-teen discordance for driving conditions and teen risky driving. Initial
      establishment of restrictions and agreement with them may have longer term
      protective effects against teen driving risk.

PMID- 16893317
TI  - Clinic-based treatment for opioid dependence: a qualitative inquiry.
AB  - OBJECTIVES: To identify barriers and facilitators to treatment of opioid
      dependence in primary care clinics. METHODS: In-depth interviews with 27 New York
      State clinic directors. RESULTS: Stigmatizing attitudes emerged as a major
      barrier. Respondents often viewed opioid-dependent persons as manipulative,
      demanding, and disruptive. Commonly cited facilitators were physician training,
      increased office staffing, and greater mental health, social services, and
      addictions support. CONCLUSIONS: Our study reveals attitudinal barriers to
      address and supportive factors to promote in order to increase the limited
      availability of office-based treatment of opioid dependence in the United States
      compared with other countries.

PMID- 16893321
TI  - Nontypeable Haemophilus influenzae meningitis complicated by hearing loss in a 9
      year-old HIV-infected boy.
AB  - A 9-year old boy with perinatal HIV infection developed meningitis due to
      nontypeable Haemophilus influenzae. His course was complicated by progressive
      hearing loss due to labyrinthitis ossificans. Placement of cochlear implant
      improved hearing thresholds. Nontypeable H. influenzae meningitis and use of
      cochlear implants have not previously been in HIV-infected children.

PMID- 16893322
TI  - Benign lymphoepithelial parotid lesions in vertically HIV-infected patients.
AB  - Benign lymphoepithelial parotid lesions (BLL) are frequently reported in HIV
      infected patients, although their clinical and prognostic significance in HIV
      infection has not been clearly defined. Ultrasonography (USG) has been shown to
      be a reliable method in monitoring the progression of such lesions. The purpose
      of this study was to describe the spectrum of sonographic and Doppler findings
      and to monitor any clinically evident physical change of parotid glands in a
      cohort of congenitally HIV-infected patients taking antiretroviral therapy. USG
      findings-based on their severity-have been grouped in three different patterns
      (0, 1, 2). Our cohort consisted of 51 patients with HIV in various Centers for
      Disease Control (CDC) stages and being given different antiretroviral protocols.
      The median USG follow-up was 36 months. The most frequent USG pattern was
      aspecific parotid gland enlargement (type 0, 45,1%). Patients with either lower
      CD4+ % (p < 0.20) and higher absolute and percent CD8+ cell count (p < 0.001 and
      p < 0.003) presented more frequently a type 2 USG pattern. None of them had any
      symptoms ascribed to "sicca syndrome" and only one patient developed non
      Hodgkin's lymphoma during the follow-up, although his USG pattern at baseline was
      type 0. In summary, the spectrum of USG findings of BLL in vertically HIV
      infected patients is broad. Because of the reported, although rare, possible
      malignant transformation of BLL in HIV-infected children, it is advisable to
      perform-even in asymptomatic patients-USG at least once per year or in
      concomitance with any physical modification of the parotid lesions.

PMID- 16893323
TI  - Switch from efavirenz to nevirapine associated with resolution of efavirenz
      related neuropsychiatric adverse events and improvement in lipid profiles.
AB  - In a large HIV-specialty private practice, patients with undetectable or low
      grade-positive viral loads with neuropsychiatric side effects or elevated lipids
      were switched from efavirenz-to nevirapine-based antiretroviral regimens. This is
      a retrospective analysis of virologic efficacy and changes in adverse
      neuropsychiatric effects and serum lipid levels after this switch. Forty patients
      were evaluated. Thirty-six had undetectable viral loads prior to the treatment
      switch, and their levels remained undetectable after the switch for a median of
      25 months (range, 6 to 59 months). Four patients had persistently low-grade
      positive viral loads before the switch; viral loads in two of the four patients
      remained low-grade-positive, while the levels in two patients became
      undetectable. Twenty patients reporting neuropsychiatric symptoms (depression,
      anxiety, or fatigue with or without sleep disturbances) before the switch
      demonstrated significant improvement, with complete resolution of symptoms in 15
      patients. Four patients with isolated sleep disturbances had significant
      improvement. No rash developed in any patient during the switch. Mean lipid
      levels improved significantly following the switch. Mean total cholesterol
      decreased 17.8 mg/dL; low-density lipoprotein cholesterol decreased 25.5 mg/dL;
      triglycerides decreased 70.1 mg/dL; and high-density lipoprotein cholesterol
      increased 5.3 mg/dL (all p < 0.05). These results demonstrate that patients who
      are virologically controlled on efavirenz-containing regimens with treatment
      associated side effects can be successfully switched to nevirapine-containing
      therapy with maintenance of virologic control, reduction in neuropsychiatric side
      effects, and improvement in dyslipidemia.

PMID- 16893324
TI  - Sexual risk and HIV acquisition among men who have sex with men travelers to Key
      West, Florida: a mathematical modeling analysis.
AB  - The present study investigated the sexual risk behaviors of men who have sex with
      men (MSM) traveling to a popular gay tourist destination in the United States. In
      2004, a brief survey was administered to 247 MSM tourists recruited from gay
      oriented venues in Key West, Florida. Data collected included demographics, HIV
      status, length of stay, substance use, and sexual risk behaviors. A probabilistic
      model of HIV transmission was used to translate participants' reports of their
      sexual behaviors while in Key West into estimates of their risk of acquiring HIV.
      Twenty-two percent of participants reported anal sex with multiple partners over
      a relatively brief period (M = 4.1 days), and approximately one third reported
      having sex with a partner met during the vacation period. Modeling analyses
      suggested that sexual activity among vacationing MSM would account for
      approximately 201 new HIV infections among MSM visitors to Key West each year.
      Although previous studies have documented sexual risk behavior in travelers,
      quantitative estimates of the impact of these behaviors on the spread of HIV are
      lacking. Findings suggest that the risk-taking behavior of MSM on vacation may
      play an important role in the dissemination of HIV and other sexually transmitted
      diseases (STDs). Future research should assess additional factors (e.g., use of
      highly active antiretroviral therapy) that may affect HIV transmission in MSM
      travelers. In addition, efforts are needed to develop effective risk-reduction
      interventions for this population.

PMID- 16893325
TI  - Prevalence of hepatitis C virus infection among men who have sex with men at a
      Boston community health center and its association with markers of high-risk
      behavior.
AB  - The present study sought to investigate the prevalence of hepatitis C virus (HCV)
      among men who have sex with men (MSM) seen at a community health center, and to
      examine risk factors associated with infection. The study population included 218
      MSM who were screened for HCV infection during routine clinic visits from May
      through December, 2001. Eighty-four percent of those screened (n = 183) agreed to
      complete a self-report questionnaire assessing drug use, sexual practices, and
      medical history. Participants ranged in age from 22 to 54 years. The majority of
      participants (82%) self-identified as Caucasian and 35% were HIV-positive.
      Prevalence of HCV infection was 11.5%. Men infected with HCV were more likely
      than HCV uninfected men to be coinfected with HIV and hepatitis B, and to have a
      history of rectal or urethral gonorrhea. HCV-infected men were more likely to
      have seen blood on shared cocaine straws and to have used crack cocaine in the
      past 6 months. Overall, 12% of HCV-infected men reported no parenteral risk
      factors for HCV infection. HCV seropositivity was significantly associated with
      an aggregate score representing high-risk behavior in the past six months. HCV
      prevention and screening should target MSM engaging in high-risk sex. Conversely,
      HIV and sexually transmitted infection risk reduction interventions should be
      targeted at MSM with HCV.

PMID- 16893326
TI  - Effects of lipodystrophy on quality of life and depression in HIV-infected men on
      HAART.
AB  - The aim of the study was a prospective assessment of the possible consequences of
      a diagnosis of lipodystrophy on health-related quality of life (HRQL) and
      depressive symptomatology in HIV-seropositive men who have sex with men. A
      standardized physical assessment for lipodystrophy was introduced within a
      prospective study in April 1999. Over a 2-year follow- up, 37 HIV-seropositive
      men who met the criteria for lipodystrophy were longitudinally compared to 92 HIV
      seropositive men without lipodystrophy and 88 HIV-seronegative men on measures of
      HRQL and depression. A series of questionnaires, which included the Medical
      Outcomes Study Short-Form 36 (SF-36) and the Center for Epidemiological Studies
      Depression (CES-D), were administered to assess HRQL and depression,
      respectively. SF-36 scores were summarized using the mental and physical
      components; CES-D results were reported as both dichotomous (with or with
      clinical depression) and continuous scores. Neither the mental nor physical
      components of the SF-36 showed any significant differences between patients with
      lipodystrophy versus HIV-seropositive patients without lipodystrophy. Similarly,
      lipodystrophy status was not significantly associated with either continuous
      depression scores or presence of clinical depression. However, consistent with
      previous results, HIV-seropositive men without lipodystrophy (compared to HIV
      seronegative men) reported higher scores on both components of the SF-36 scales
      and both categorizations of the CES-D. The results of this study suggest that
      lipodystrophy does not negatively affect HRQL or depression, above and beyond,
      the diagnosis of HIV infection, although the impact of the severity of
      lipodystrophy on these conditions will require further study.

PMID- 16893328
TI  - Determinants of survival for Native American adults with HIV infection.
AB  - Few if any Native American/Alaska Native (NA/AN) people have been included in
      highly active antiretroviral therapy (HAART) treatment trials or epidemiologic
      studies, leaving little data on which to be assured of the efficacy of HAART in
      this unique population. This study aims to evaluate the impact of HAART and
      review determinants of survival in a cohort of NA/AN persons receiving treatment
      for HIV in a real life clinical setting. A retrospective chart review of 235 HIV
      infected Native Americans receiving services at an urban medical center operated
      by the Indian Health Service from January 1, 1981 through June 30, 2004 was
      conducted, providing 782.7 person-years of follow-up. The main outcome measures
      were time from study entry and from incident AIDS diagnosis to death. Death rates
      fell from 18.4 (13.3-25.4) per 100 person-years in the period prior to 1998 to
      6.4 (4.6-8.8) per 100 person-years in the years 1998-2004, (RR 0.35, p < 0.0001).
      Factors associated with the greatest reduction in risk of death from time of
      study entry were current use of HAART, HR 0.13 (0.06-0.30, p < 0.001), and CD4
      count >/=200 at entry, HR 0.16 (0.08-0.35, p < 0.001). Current use of HAART was
      the strongest predictor of survival from time of AIDS diagnosis, HR 0.11 (0.05
      0.25, p < 0.001). The use of HAART therapy and CD4 count were primary predictors
      of survival. Earlier diagnosis and access to effective medical treatment will be
      key factors in reducing disparities in health brought about by HIV infection in
      Native American/Alaska Native communities.

PMID- 16893327
TI  - Detection of HIV-1 in injection paraphernalia: risk in an era of heightened
      awareness.
AB  - Links between AIDS and self-injection of drugs were first recognized more than 20
      years ago, but identification of a specific pathogen and ways to neutralize it
      has not led to complete success in preventing transmission of HIV-1 infection
      among injecting drug users (IDUs). A street ethnographer identified active risk
      locales (places where IDUs go to inject drugs) and recruited their proprietors
      into a study of contaminated injection paraphernalia. Collected paraphernalia
      from locales were analyzed for contamination by HIV-1 using real-time polymerase
      chain reaction (PCR). Proprietors and clientele of 16 risk locales participated
      by contributing used paraphernalia and/or agreeing to a blood test (0.5-1 mL
      drawn by finger stick). Realtime PCR was the primary measure used to determine
      contamination of injection paraphernalia and blood samples with HIV-1. Of 130
      samples collected at baseline, a total of 8 were found to have evidence of HIV-1
      contamination by detection of either HIV-1 RNA or DNA. The most serious
      contamination (up to 600,000 copies per milliliter) was found in ancillary
      paraphernalia, rather than needle/syringe (N/S) specimens. Only 4 of 74 N/S
      specimens had any evidence of HIV-1 contamination at all (with very low viral
      loads), and none had both HIV-1 DNA and RNA. Although IDUs in risk locales in
      Miami/Dade appear to be taking care of their N/S with regard to contamination by
      HIV-1, important evidence of contamination in ancillary paraphernalia, especially
      cookers and cottons, indicates that IDUs may still incur serious risk regardless
      of how well they care for their N/S. Our observations indicated that IDUs rinsed
      their N/S before returning them to the proprietors, from whom we eventually
      collected them, and this rinsing would have masked the contamination to which
      they were exposed through use of unrinsed cookers and reused cottons.

PMID- 16893329
TI  - Kaletra approval in Europe.

PMID- 16893330
TI  - Companies treating more employees with HIV/AIDS.

PMID- 16893331
TI  - Insights from the 2006 disease management colloquium.

PMID- 16893332
TI  - Health-related quality of life and treatment compliance with diabetes care.
AB  - The objective of this study was to explore the relationship between health
      related quality of life (HRQOL) and treatment compliance among a sample of
      patients with diabetes. A sample of 198 employees with diabetes of a large
      southeastern health plan, who were continuously enrolled in 2004, was surveyed
      using the Short Form Health Survey (SF-12)--a measure of HRQOL. Of the 198
      identified members, 111 (56%) completed and returned the SF-12. Treatment
      compliance was measured using medical claims data. Compliance scores were then
      calculated as the number of American Diabetes Association (2005) recommended
      guidelines completed in 2004. These guidelines include two hemoglobin tests, a
      cholesterol test, a microalbuminuria test, and an eye exam. Compliance scores
      ranged from zero (no treatments) to five (all treatments). Both age and the
      Mental Composite Score (MCS) of the SF-12 were significant predictors of
      compliance. Age was positively related to compliance, which means that compliance
      with treatment guidelines increases as a person ages. MCS was negatively related
      to compliance, which means that those who score lower on the MCS are more likely
      to be compliant with diabetes care. Results of this pilot study indicate that
      disease management programs may need to focus special attention on those people
      with diabetes who are younger and have better mental health. Moreover, factors
      other than past utilization of care or predicted costs may be beneficial to
      consider in the inclusion criteria for disease management programs.

PMID- 16893333
TI  - Anticoagulation management: a new approach.
AB  - Anticoagulation therapy has been identified as an area in which new approaches to
      treatment and monitoring may allow for significant improvements in healthcare
      quality and costs. We evaluated the potential benefits of a new approach to
      anticoagulation therapy, utilizing decision support software, point-of-service
      testing, and workflow redesign. We performed an intervention study in the setting
      of a university-affiliated primary care clinic, involving 40 patients receiving
      chronic anticoagulation therapy. Study measurement included anticoagulation
      control, complications of therapy and related costs, as well as clinic revenue
      and overhead costs. After implementation of the new approach, the frequency of
      international normalized ratio (INR) results within therapeutic range increased
      from 34% to 67%. During a 1-year follow-up period, complications related to
      anticoagulation therapy were reduced by 91% (p < 0.01). Labor-related overhead
      costs decreased from approximately 12,600 to 3,100 US dollars. During the same
      period, the clinic generated approximately 35,000 US dollars in new revenue. For
      every dollar spent on clinic implementation and maintenance, over 25 US dollars
      was returned from cost containment and new revenue production. This approach
      allows a clinic to show improved anticoagulation control and complication rates
      while simultaneously improving financial performance.

PMID- 16893334
TI  - Evolution of clinical practice guidelines: evidence supporting expanded use of
      medicines.
AB  - Previous studies have shown that the primary factor underlying increased spending
      on pharmaceuticals has been the rising utilization of medications, rather than
      increases in unit drug price. This study examined the evolution of clinical
      practice guidelines to assess possible reasons for the rising drug volume.
      Clinical practice guidelines from 1970 to the present were reviewed for the six
      most prevalent treatable medical conditions/risk factors listed as priority areas
      by the Institute of Medicine. We searched the National Guidelines Clearinghouse,
      PubMed and Medline databases, and Web sites of relevant national organizations
      for US clinical practice guidelines published through January 2005. Information
      pertaining to the therapeutic regimen (eg, the frequency and duration of
      recommended treatment, when treatment should be initiated, the patient population
      for whom the guideline was intended) was abstracted and entered into evidence
      tables. Changes in guidelines were distributed across three themes that
      recommended evidence-based increases in medication use, including: (1) changes in
      the size of the treatable population; (2) changes in the number and type of
      recommended pharmaceutical therapeutic options, including movement from
      monotherapy to combination therapy, treatment of comorbidities, and use of newer
      types of medicines; and (3) changes in the therapeutic regimen, including a shift
      from episodic care to preventive and chronic care. Many of these changes point to
      an important, but not often noticed, addition of secondary prevention of disease
      effects to the objectives of medical care. These trends are likely to continue
      with important economic, clinical, and policy ramifications.

PMID- 16893335
TI  - Predicting hospitalization and mortality in end-stage renal disease (ESRD)
      patients using an Index of Coexisting Disease (ICED)-based risk stratification
      model.
AB  - We evaluated the use of an additive Index of Coexisting Diseases (ICED)-based
      stratification schema to determine subsequent hospitalization and mortality in a
      hemodialysis population. Patients from five commercial health plans were
      stratified into low-, medium-, and high-risk groups and followed for up to 1
      year. Patients were reassessed and restratified at 90-day intervals and censored
      when disease management ceased. Outcome measures collected through selfreports
      and health plan records were captured in an active database. Survival to first
      hospitalization/ mortality was compared by Kaplan Meier curves, survivor function
      differences by the Wilcoxon test, and group comparisons by ANOVA and chi square.
      Population characteristics included mean age of 63.0, 57.7% male, and 58.8%
      diabetic. Mortality was 13.0% per patient year (standardized mortality ratio
      0.43) and the hospitalization rate was 0.59 per patient year (standardized
      hospitalization ratio 0.24). Survival curves demonstrated differences in
      mortality and hospitalization between the patients in different initial risk
      categories (p < 0.01). Mean hospitalizations were 0.81 +/- 1.53 per patient year
      (high risk), 0.45 +/- 0.99 (medium risk), and 0.15 +/- 0.51 for the low-risk
      group (p < 0.001). Stratification was dynamic; 47.3% decreased and 4.7% increased
      risk level between the first and second assessment. These changes were associated
      with survival differences for initial low (p = 0.06) or medium patients (p <
      0.01), and hospital-free survival for initial medium (p = 0.08) or high patients
      (p < 0.05). In conclusion, this ICED-based stratification schema predicted
      mortality and hospitalization for hemodialysis patients participating in our
      disease management program.

PMID- 16893337
TI  - Using individualized predictive disease modeling to identify patients with the
      potential to benefit from a disease management program for diabetes mellitus.
AB  - Diabetes is an increasing health problem, but efforts to handle this pandemic by
      disease management programs (DMP) have shown conflicting results. Our hypothesis
      is that, in addition to a program's content and setting, the choice of the right
      patients is crucial to a program's efficacy and effectiveness. We used
      individualized predictive disease modeling (IPDM) on a cohort of 918 patients
      with type 2 diabetes to identify those patients with the greatest potential to
      benefit from inclusion in a DMP. A portion of the patients (4.7%) did not have
      even a theoretical potential for an increase in life expectancy and would
      therefore be unlikely to benefit from a DMP. Approximately 16.1% had an increase
      in life expectancy of less than half a year. Stratification of the entire cohort
      by surrogate parameters like preventable 10-year costs or gain in life expectancy
      was much more effective than stratification by classical clinical parameters such
      as high HbA1c level. Preventable costs increased up to 50.6% (or 1,010 per
      patient (1 = US dollars 1.28), p < 0.01) and life expectancy increased up to
      54.8% (or 2.3 years, p < 0.01). IPDM is a valuable strategy to identify those
      patients with the greatest potential to avoid diabetes-related complications and
      thus can improve the overall effectiveness and efficacy of DMPs for diabetes
      mellitus.

PMID- 16893336
TI  - Cost-savings analysis of an outpatient management program for women with
      pregnancy-related hypertensive conditions.
AB  - The aim of this study was to evaluate the cost savings of outpatient management
      services for women with pregnancy-related hypertensive conditions. The outpatient
      management program included verbal and written patient education related to the
      hypertensive disease process during pregnancy as well as self-care procedures.
      Biometric data (ie, automated blood pressure measurement, qualitative urine
      protein) were collected at least daily by the patient and transmitted
      telephonically to a nursing call center. Data were evaluated and subjective
      symptoms assessed daily. Electronic records were maintained and reports provided
      to the prescribing physician and case manager. Included for analysis were:
      patients with pregnancy-related hypertensive conditions receiving outpatient
      services between January 1999 and November 2003, singleton gestation, no history
      of chronic hypertension, and gestational age of 20.0-36.9 weeks at start of
      outpatient program (n = 1,140). Maternal characteristics, antenatal
      hospitalization and length of stay, progression of disease, and neonatal outcome
      were analyzed. To evaluate cost-effectiveness, a model was developed to compare
      the cost of the program plus adjunctive antenatal hospitalization, to control
      data. The mean gestational age at program start was 32.6 weeks. Antenatal
      hospital admission was required for 24.8% of patients, with a mean length of stay
      of 2.3 days per admission. Progression to severe preeclampsia occurred in 14.3%
      of patients. Mean gestational age at delivery was 37.0 weeks. Antepartum charges
      averaged 10,327 US dollars per control patient and 4,888 US dollars per program
      patient, a difference of 5,439 US dollars. For each dollar spent on outpatient
      management, an average of 2.50 US dollars was saved. Utilizing outpatient
      management services for women with pregnancy-related hypertension reduces the
      need for inpatient care and is cost-effective.

PMID- 16893339
TI  - Therapeutic approaches to peripheral neuropathy based on neuroactive steroids.
AB  - '...a possible therapeutic approach for peripheral neuropathy might be
      represented by the treatment with neuroactive steroids themselves, with molecules
      able to induce their in situ synthesis or with molecules able to interact with
      their receptors.'

PMID- 16893341
TI  - Ziprasidone: efficacy and safety in patients with bipolar disorder.
AB  - Atypical antipsychotics have been increasingly shown to have efficacy in the
      treatment of various phases of bipolar disorder. Ziprasidone acts primarily
      through serotonergic and dopaminergic receptor antagonism, and exerts effects as
      an inhibitor of serotonin and norepinephrine reuptake. Ziprasidone exhibits dose
      proportional, linear changes in exposure and is hepatically metabolized primarily
      by aldehyde oxidase. In studies of patients with acute manic or mixed episodes,
      treatment with ziprasidone monotherapy or in combination with lithium, resulted
      in rapid symptom improvement and was generally well tolerated. Results from open
      label extension studies of ziprasidone indicate continued improvement in manic
      symptoms. Preliminary data in pediatric patients with bipolar disorder also
      suggest it may be efficacious in this population. Ziprasidone is considered as a
      first-line treatment option in patients with bipolar manic or mixed episodes,
      with or without psychosis and displays a favorable side-effect profile.

PMID- 16893342
TI  - Sodium oxybate for narcolepsy.
AB  - Sodium oxybate (Xyrem), also known as gamma-hydroxybutyric acid, is the only
      therapeutic specifically approved in the USA for the treatment of cataplexy in
      narcolepsy. The US FDA has recently expanded its indication to include excessive
      daytime sleepiness associated with narcolepsy. In contrast to the antidepressants
      and stimulants commonly used to treat the disorder, sodium oxybate is the only
      compound that addresses both sets of symptoms and, when used properly, is less
      likely to lead to the development of tolerance and other undesirable side
      effects. In this review, the results of clinical trials and the place of sodium
      oxybate in narcolepsy treatment are discussed.

PMID- 16893343
TI  - Migraine preventive therapy: selection of appropriate patients and general
      principles of management.
AB  - The goal of this review is to communicate the rationale and the possible benefits
      of migraine preventive treatments to clinicians and patients, and to address the
      many problematic issues created by missed diagnosis or misdiagnoses and
      inadequate migraine management. Successful implementation of migraine preventive
      treatment requires appropriate patient selection based on several factors,
      including the frequency of migraine attacks (> or =2-3 attacks/month), the level
      of disability incurred and the frequency of acute medication usage.
      Unfortunately, several epidemiologic surveys indicate that preventive therapies
      are significantly underutilized, which supports the need for greater dialog
      concerning migraine prevention between consumers and physicians. Effective
      migraine preventive therapy should reduce the frequency, duration, and severity
      of migraine, and also improve function, reduce disability, and possibly reduce
      the risk of worsening the headache syndrome, through acute medication overuse.

PMID- 16893344
TI  - Functional neuroimaging of primary headache disorders.
AB  - Until recently, primary headache disorders, such as migraine and cluster headache
      were considered to be vascular in origin. However, advances in neuroimaging
      techniques, such as positron emission tomography, single photon emission computed
      tomography and functional magnetic resonance imaging have augmented the growing
      clinical evidence that these headaches are primarily driven from the brain. This
      review covers functional imaging studies in migraine, cluster headache, rarer
      headache syndromes and experimental head pain. Together with newer techniques,
      such as voxel-based morphometry and magnetic resonance spectrometry, functional
      imaging continues to play a role in elucidating and targeting the neural
      substrates in each of the primary headache syndromes.

PMID- 16893345
TI  - Blood pressure disorders during Parkinson's disease: epidemiology,
      pathophysiology and management.
AB  - Blood pressure disorders are highly prevalent in the course of Parkinson's
      disease (PD). They relate to autonomic failure and are frequently associated with
      orthostatic hypotension, postprandial hypotension and supine hypertension. Supine
      hypertension, which may concern up to 50% of patients with PD and autonomic
      failure, is driven by residual sympathetic activity and changes in sensitivity of
      vascular adrenergic receptors. It can also be induced or worsened by
      antihypotensive drugs. Even if little data is available, a set of arguments
      suggests that supine hypertension sometimes requires treatment. This review will
      focus on recent data on the pathophysiology and the management of supine
      hypertension in the context of its association with orthostatic hypotension.

PMID- 16893346
TI  - Treatment of advanced Parkinson's disease.
AB  - Parkinson's disease is a progressive neurological disorder characterized by
      tremor, bradykinesia, rigidity, gait and postural instability and a variety of
      nonmotor symptoms. While these and other motor signs typically improve with
      levodopa, the so-called axial signs, such as dysarthria, dysphagia, postural
      instability and freezing, and most nonmotor signs, such as depression, cognitive
      decline and dysautonomia, usually do not respond satisfactorily to levodopa.
      Furthermore, the use of levodopa may be limited by the development of motor
      fluctuations, dyskinesias and other adverse effects. This manuscript reviews the
      medical management of advanced Parkinson's disease, focusing on the treatment of
      motor fluctuations and dyskinesias and of nonmotor and nonlevodopa responsive
      symptoms.

PMID- 16893347
TI  - Blood-brain barrier and chemotherapeutic treatment of brain tumors.
AB  - The blood-brain barrier (BBB) is of pivotal importance to maintain homeostasis of
      the CNS, as it closely regulates the composition of the interstitial fluid in the
      brain. Unfortunately, malignancies that grow within the CNS may evade
      chemotherapeutic drugs using the same barrier, making this disease refractory to
      most chemotherapy regimens. This review will outline the impact of the BBB in
      brain cancer and discuss the efforts that have been made to enhance the drug
      exposure of brain tumors. Although this review will focus on the role of the BBB
      in primary brain cancer (malignant glioma), its impact on brain metastases will
      also be briefly discussed.

PMID- 16893348
TI  - Current treatment approaches to early childhood medulloblastoma.
AB  - Treatment of medulloblastoma, the most common malignant brain tumor of childhood,
      is particularly challenging in very young children, owing to the increased
      susceptibility of the immature brain to treatment-induced neurocognitive
      deficits. Three promising strategies have been developed in combination with
      systemic postoperative chemotherapy, to avoid craniospinal irradiation for young
      children with nonmetastatic medulloblastoma, these include: high-dose
      chemotherapy, with and without local radiotherapy; intraventricular chemotherapy;
      and local radiotherapy. More intensified strategies may be required for
      metastatic medulloblastoma. Future studies will clarify the prognostic relevance
      of desmoplasia, postoperative residual tumor and biological markers to improve
      stratification criteria by risk-adapted treatment recommendations. An
      international Phase III trial for young children with nonmetastatic
      medulloblastoma, comparing survival rates and neurocognitive outcomes of
      different treatment strategies by standardized criteria, is under discussion.

PMID- 16893350
TI  - Conundrums in community-acquired pneumonia.

PMID- 16893349
TI  - Prevention and treatment of post-traumatic epilepsy.
AB  - Post-traumatic epilepsy is reported after 2-5% of closed head injuries but up to
      50% or more following penetrating head injury. Despite several studies, no drug
      strategy has been able, to date, to quench the biochemical events leading to
      epileptogenesis. One possibility is that treatment with available antiepileptic
      drugs has been implemented too late, and thus, ultra-early treatment might still
      be able to stop the neurochemical epileptogenic cascade dead in its tracks.
      However, currently drug therapy should be instituted only after the first late
      unprovoked seizure.

PMID- 16893351
TI  - Epidemic Clostridium difficile.

PMID- 16893352
TI  - Out-of-hospital cardiac arrest in Victoria: rural and urban outcomes.
AB  - OBJECTIVE: To compare the survival rate from out-of-hospital cardiac arrest in
      rural and urban areas of Victoria, and to investigate the factors associated with
      these differences. DESIGN: Retrospective case series using data from the
      Victorian Ambulance Cardiac Arrest Registry. SETTING: All out-of-hospital cardiac
      arrests occurring in Victoria that were attended by Rural Ambulance Victoria or
      the Metropolitan Ambulance Service. PARTICIPANTS: 1790 people who suffered a
      bystander-witnessed cardiac arrest between January 2002 and December 2003.
      RESULTS: Bystander cardiopulmonary resuscitation was more likely in rural (65.7%)
      than urban areas (48.4%) (P = 0.001). Urban patients with bystander-witnessed
      cardiac arrest were more likely to arrive at an emergency department with a
      cardiac output (odds ratio [OR], 2.92; 95% CI, 1.65-5.17; P < 0.001), and to be
      discharged from hospital alive than rural patients (urban, 125/1685 [7.4%];
      rural, 2/105 [1.9%]; OR, 4.13; 95% CI, 1.09-34.91). Major factors associated with
      survival to hospital admission were distance of cardiac arrest from the closest
      ambulance branch (OR, 0.87; 95% CI, 0.82-0.92), endotracheal intubation (OR,
      3.46; 95% CI, 2.49-4.80), and the presence of asystole (OR, 0.50; 95% CI, 0.38
      0.67) or pulseless electrical activity (OR, 0.73; 95% CI, 0.56-0.95) on arrival
      of the first ambulance crew. CONCLUSIONS: Survival rates differ between urban and
      rural cardiac arrest patients. This is largely due to a difference in ambulance
      response time. As it is impractical to substantially decrease response times in
      rural areas, other strategies that may improve outcome after cardiac arrest
      require investigation.

PMID- 16893354
TI  - Long-term trends in Indigenous deaths from chronic diseases in the Northern
      Territory: a foot on the brake, a foot on the accelerator.
AB  - OBJECTIVE: To examine trends in Northern Territory Indigenous mortality from
      chronic diseases other than cancer. DESIGN: A comparison of trends in rates of
      mortality from six chronic diseases (ischaemic heart disease [IHD], chronic
      obstructive pulmonary disease [COPD], cerebrovascular disease [CVD], diabetes
      mellitus [DM], renal failure [RF] and rheumatic heart disease [RHD]) in the NT
      Indigenous population with those of the total Australian population.
      PARTICIPANTS: NT Indigenous and total Australian populations, 1977-2001. MAIN
      OUTCOME MEASURES: Estimated average annual change in chronic disease mortality
      rates and in mortality rate ratios. RESULTS: Death rates from IHD and DM among NT
      Indigenous peoples increased between 1977 and 2001, but this increase slowed
      after 1990. Death rates from COPD rose before 1990, but fell thereafter. There
      were non-significant declines in death rates from CVD and RHD. Mortality rates
      from RF rose in those aged > or = 50 years. The ratios of mortality rates for NT
      Indigenous to total Australian populations from these chronic diseases increased
      throughout the period. CONCLUSIONS: Mortality rates from IHD and DM in the NT
      Indigenous population have been increasing since 1977, but there is evidence of a
      slower rise (or even a fall) in death rates in the 1990s. These early small
      changes give reason to hope that some improvements (possibly in medical care)
      have been putting the brakes on chronic disease mortality among Aboriginal and
      Torres Strait Islander peoples.

PMID- 16893353
TI  - The burden of chronic kidney disease in Australian patients with type 2 diabetes
      (the NEFRON study).
AB  - OBJECTIVE: To estimate the frequency of chronic kidney disease (CKD) in a clinic
      based sample of patients with type 2 diabetes in the setting of Australian
      primary care. DESIGN, SETTING AND PARTICIPANTS: Expressions of interest were
      invited from all registered general practitioners in Australia: 500 GP
      investigators were randomly selected from each stratum (state and urban versus
      rural location), proportional to the census population, and asked to recruit and
      provide data for 10-15 consecutively presenting adults with type 2 diabetes
      between April and September 2005. MAIN OUTCOME MEASURES: Estimated glomerular
      filtration rate (eGFR) less than 60 mL/min/1.73 m(2) and evidence of kidney
      damage on urinalysis (eg, microalbuminuria). RESULTS: 348 GP investigators
      submitted data for 3893 individuals with type 2 diabetes (52% men; median age, 66
      years). Almost one in every four patients consulting their GPs had an eGFR < 60
      mL/min/1.73 m(2) (23.1%; 95% CI, 21.8%-24.5%). More than one in three had an
      elevated urinary albumin-creatinine ratio (ACR) (34.6%; 95% CI, 33.3%-35.9%).
      There was an overlap of 10.4% of patients with both an eGFR < 60 mL/min/1.73 m(2)
      and an elevated urinary ACR, meaning that almost one in two patients with type 2
      diabetes consulting their GPs (47.1%; 95% CI, 45.8%-48.4%) had CKD. CKD was
      significantly more common in women, in older people, and in individuals with
      established macrovascular disease. CONCLUSION: CKD is a common complication of
      type 2 diabetes, found in about half of all patients with type 2 diabetes
      consulting their GPs. Efforts to increase the recognition of CKD will lead to
      improved care, and possibly survival, of patients with type 2 diabetes.

PMID- 16893356
TI  - A journey of Indigenous identity.

PMID- 16893357
TI  - Retractions in the research literature: misconduct or mistakes?
AB  - OBJECTIVE: To determine how commonly articles are retracted on the basis of
      unintentional mistakes, and whether these articles differ from those retracted
      for scientific misconduct in authorship, funding, type of study, publication, and
      time to retraction. DATA SOURCE AND STUDY SELECTION: All retractions of English
      language publications indexed in MEDLINE between 1982 and 2002 were extracted.
      DATA EXTRACTION: Two reviewers categorised the reasons for retraction of each
      article as misconduct (falsification, fabrication, or plagiarism) or
      unintentional error (mistakes in sampling, procedures, or data analysis; failure
      to reproduce findings; accidental omission of information about methods or data
      analysis). DATA SYNTHESIS: Of the 395 articles retracted between 1982 and 2002,
      107 (27.1%) were retracted because of scientific misconduct, 244 (61.8%) because
      of unintentional errors, and 44 (11.1%) could not be categorised. Compared with
      articles retracted because of misconduct, articles with unintentional mistakes
      were more likely to have multiple authors, no reported funding source, and to be
      published in frequently cited journals. They were more likely to be retracted by
      the author(s) of the article, and the retraction was more likely to occur more
      promptly (mean, 2.0 years; 95% CI, 1.8-2.2) than articles withdrawn because of
      misconduct (mean, 3.3 years; 95% CI, 2.7-3.9) (P < 0.05 for all comparisons).
      CONCLUSIONS: Retractions in the biomedical literature were more than twice as
      likely to result from unintentional mistakes than from scientific misconduct. The
      different characteristics of articles retracted for misconduct and for mistakes
      reflect distinct causes and, potentially, distinct solutions.

PMID- 16893358
TI  - Increased expenditure on Australian health and medical research and changes in
      numbers of publications determined using PubMed.
AB  - OBJECTIVE: To determine temporal trends in PubMed publications for Australian
      authors compared with changes in funding for health and medical research (HMR).
      DESIGN: Retrospective observational study. SETTING: Internet-based bibliometric
      study that collated Australian HMR expenditure from the Australian Institute of
      Health and Welfare and Australian (and other) research publications from PubMed.
      MAIN OUTCOME MEASURES: Australian expenditure on HMR and numbers of PubMed-cited
      publications from 1980 to 2004, with subgroup analyses for universities, clinical
      trials, and genetic and biotechnology research, and comparison with similar
      results from the United Kingdom and New Zealand. RESULTS: From 1980-81 to 2003
      04, Australian HMR expenditure increased from $66 million to $1503 million and
      total Australian PubMed publications increased from 844 to 13 836. From 1995-96
      to 2003-04, Australian publications for university-derived research and for
      clinical trials increased at a fairly constant rate. Genetic and biotechnology
      publications increased about fivefold (49 to 277) between 1990-91 and 2003-04.
      Between 1990 and 2004, total publications increased from 1754 to 3288 for New
      Zealand and from 12 401 to 19 600 for the UK. CONCLUSIONS: There is an
      association between increased funding for HMR and increased publications, as
      determined using PubMed, in the past 10 years. Using PubMed may be a simple way
      to track output from HMR expenditure.

PMID- 16893359
TI  - Insulin levels in insulin resistance: phantom of the metabolic opera?
AB  - Insulin resistance is considered a core component in the pathophysiology of the
      metabolic syndrome. Some clinicians measure serum insulin concentrations in the
      mistaken belief that they can be used to diagnose insulin resistance. Serum
      insulin levels are poor measures of insulin resistance. Furthermore, there is no
      clinical benefit in measuring insulin resistance in clinical practice.
      Measurements of fasting serum insulin levels should be reserved for large
      population-based epidemiological studies, where they can provide valuable data on
      the relationship of insulin sensitivity to risk factors for diabetes and
      cardiovascular disease. Clinicians should shift from identifying "insulin
      resistance" to identifying risk factors, such as fasting glucose and lipid
      levels, hypertension and central obesity. These proven risk factors converge
      within the metabolic syndrome. Individuals "at risk" of diabetes and
      atherosclerotic cardiac disease can be identified simply and inexpensively, using
      classic clinical techniques, such as history-taking, physical examination, and
      very basic investigations.

PMID- 16893361
TI  - Teaching on the run tips 14: teaching in ambulatory care.

PMID- 16893360
TI  - Surgical service centralisation in Australia versus choice and quality of life
      for rural patients.
AB  - High patient volume for both hospitals and surgeons is an important determinant
      of operative mortality and outcome for complex and infrequently performed
      operations. The 13% of Australia's population who live in rural and remote areas
      often choose to have surgery close to home and support networks despite the
      potentially higher operative mortality and morbidity. Rural patients should be
      able to make an informed choice about having their surgery locally. Rural and
      metropolitan surgeons should discuss and reach mutual agreement on where each
      patient is best treated. A balance must be struck between quality of services
      that can be provided locally and geographic convenience.

PMID- 16893362
TI  - Hazardous contact: a case of visual loss following Pseudomonas keratitis from
      novelty contact lens wear.

PMID- 16893363
TI  - Paraspinal tuberculosis.

PMID- 16893364
TI  - Microbial keratitis associated with overnight wear of silicone hydrogel contact
      lenses.

PMID- 16893365
TI  - Systemic allergy to topical hexamidine.

PMID- 16893366
TI  - TB or not TB: treat to see.

PMID- 16893367
TI  - Mycobacterium ulcerans infection: a rediscovered focus in the Capricorn Coast
      region of central Queensland.

PMID- 16893368
TI  - Clinical outcomes associated with changes in a chronic disease treatment program
      in an Australian Aboriginal community.

PMID- 16893369
TI  - Mutual obligation and Indigenous health: thinking through incentives and
      obligations.

PMID- 16893371
TI  - More doctors, but not enough: Australian medical workforce supply 2001-2012.

PMID- 16893370
TI  - Do women in rural and remote areas need different guidelines for management of
      low-grade abnormalities found on cervical screening?

PMID- 16893372
TI  - The success and unrealised potential of the National Cancer Control Initiative.

PMID- 16893373
TI  - Statin therapy in patients with chronic kidney disease: to use or not to use.
AB  - Dyslipdemia is a common complication of chronic kidney disease (CKD) and
      contributes to high cardiovascular morbidity and mortality of CKD patients.
      Experimental studies have demonstrated that lipids induce glomerular and
      tubulointerstitial injury and that lipid-lowering treatments ameliorate renal
      injury. Therapy with statins not only has the potential to lower cardiovascular
      morbidity and mortality in patients with CKD but also to slow progression of
      renal disease. Whereas the guidelines for treatment of hyperlipidaemia in
      nonrenal patients are based on prospective, randomized, placebo-controlled mega
      trials, such data are not available for CKD patients. This review outlines the
      limited information currently available on the effect of statins among patients
      with CKD and summarizes the ongoing randomized trials designed to address this
      question.

PMID- 16893374
TI  - Aminoguanidine prevents arterial stiffening in a new rat model of type 2
      diabetes.
AB  - BACKGROUND: Formation of advanced glycation end-products (AGEs) on collagen
      within the arterial wall may be responsible for the development of diabetic
      vascular injury. This study focused on investigating the role of aminoguanidine
      (AG), an inhibitor of AGE formation, in the prevention of noninsulin-dependent
      diabetes mellitus (NIDDM)-derived arterial stiffening and cardiac hypertrophy in
      rats. MATERIALS AND METHODS: The NIDDM was induced in male Wistar rats, which
      were administered intraperitoneally with 180 mg kg(-1) nicotinamide (NA) 30 min
      before an intravenous injection of 50 mg kg(-1) streptozotocin (STZ). After
      induction of diabetes mellitus type 2, animals receiving daily peritoneal
      injections with 50 mg kg(-1) AG for 8 weeks were compared with the age-matched,
      untreated, diabetic controls. RESULTS: After exposure to AG, the STZ-NA diabetic
      rats had improved aortic distensibility, as evidenced by 18.8% reduction of
      aortic characteristic impedance (P < 0.05). Treatment of the experimental
      syndrome with AG also resulted in a significant increase in wave transit time
      (+23.7%, P < 0.05) and a decrease in wave reflection factor (-26.6%, P < 0.05),
      suggesting that AG may prevent the NIDDM-induced augmentation in systolic load of
      the left ventricle. Also, the glycation-derived modification on aortic collagen
      was found to be retarded by AG. The diminished ratio of left ventricular weight
      to body weight suggested that prevention of the diabetes-related cardiac
      hypertrophy by AG may correspond to the drug-induced decline in aortic
      stiffening. CONCLUSIONS: Long-term administration of AG to the STZ-NA diabetic
      rats imparts significant protection against the NIDDM-derived impairment in
      vascular dynamics, at least partly through inhibition of the AGE accumulation on
      collagen in the arterial wall.

PMID- 16893376
TI  - Undiagnosed dysglycaemia and inflammation in cardiovascular disease.
AB  - BACKGROUND: Cardiovascular (CV) disease is associated with increased levels of
      glucose, but the prevalence of dysglycaemia in CV diseases is not fully known.
      The study examined the prevalence of unknown dysglycaemia and its association
      with inflammation in Caucasian patients with ischaemic vascular complications,
      i.e. coronary artery disease (CAD), cerebrovascular disease (CVD) and peripheral
      artery disease (PAD). MATERIALS AND METHODS: This case-controlled study involved
      149 patients (mean age 68 years) hospitalized for CAD, PAD or CVD and 59 control
      subjects (CTR) free from CV-disease. The prevalence of dysglycaemia according to
      WHO/ADA criteria (impaired fasting glycaemia, impaired glucose tolerance or
      diabetes mellitus) was assessed by a 75-g oral glucose tolerance test.
      Inflammatory parameters were analyzed in fasting samples. RESULTS: Dysglycaemia
      was found in 49%, 55% and 57% of patients with CAD, CVD and PAD, respectively;
      all were significantly higher than among the controls (29%). The odds ratio (95%
      CI) for being dysglycaemic were 1.7 (1.04-2.77), 1.9 (1.19-3.06) and 2.0 (1.25
      3.19) for CAD, CVD and PAD, respectively. Inflammatory markers (the total
      leucocyte count, soluble tumour necrosis factor-receptor type I, C-reactive
      protein) were elevated in patient groups and tended to increase with increasing
      blood glucose levels in all groups. The levels of the anti-inflammatory cytokine
      transforming growth factor-beta1 and insulin-like growth factor binding protein 3
      were lowered in patients with CAD and, in patients with PAD, the former was
      inversely related to the levels of the blood glucose. CONCLUSIONS: Undiagnosed
      dysglycaemia was common in patients with ischaemic CV manifestations regardless
      of vascular bed involved. Inflammation was associated in a dosage-related manner
      to glucose levels.

PMID- 16893375
TI  - Antibody response in patients with endocarditis caused by Staphylococcus aureus.
AB  - BACKGROUND: Staphylococcus aureus expresses a variety of adhesins involved in the
      colonization of host tissues. This study aimed to evaluate the role of
      staphylococcal surface proteins in the aetiology of infective endocarditis (IE)
      and the host immune response to infection. MATERIALS AND METHOD: The ELISA assays
      were used to assess the adherence of S. aureus isolates recovered from the blood
      cultures of 19 patients with IE (16 were drug abusers) to subendothelial matrix
      proteins. Anti-adhesin antibody titre was measured incubating surface-coated
      bacterial antigens with patients' IgG. S. aureus effects on platelet aggregation
      were evaluated with an aggregometer. RESULTS: Staphylococcus aureus isolates,
      from the patients with IE, exhibited a high expression of several surface
      components recognizing extracellular matrix proteins: clumping factors A and B
      (ClfA and ClfB) and fibronectin-binding proteins (FnbpA and FnbpB), whereas only
      four strains expressed the collagen-binding protein CNA. Bacteria also interacted
      with platelets both in the absence or presence of fibronectin or fibrinogen and
      some strongly supported platelet aggregation. Almost all patients presented
      significantly higher antibody reactivity to ClfA, ClfB, FnbpA, CNA and MAP (MHC
      class II analogous protein) than in sera from healthy individuals. On the
      contrary, the reactivity to CNA was remarkable only in three patients. The IgG
      preparations weakly inhibited the binding of bacteria to fibronectin, whereas
      they exhibited considerable blocking activity on staphylococcal attachment to
      fibrinogen or collagen. CONCLUSION: Adhesins ClfA, ClfB and FnbpA are produced in
      vivo and appear important factors both in valve colonization and in promoting
      host immune responses.

PMID- 16893377
TI  - Comparison of different cellular models measuring in vitro the whole human serum
      cholesterol efflux capacity.
AB  - BACKGROUND: Fu5AH rat hepatoma cells and cAMP (cyclic AMP)-pretreated J774 mouse
      macrophages are commonly used as models for SR-BI (scavenger receptor class B
      type I) and ABCA1 (ATP binding cassette transporter 1)-mediated free cholesterol
      efflux to whole serum, respectively. However, the responsiveness of Fu5AH,
      control or cAMP pretreated J774 cells to the various lipids and HDL (high-density
      lipoprotein)-parameters from both normo- and dyslipidaemic subjects has never
      been compared within the same study. MATERIALS AND METHODS: Fifty-eight men were
      classified into four groups: type IIa hypercholesterolaemic (n = 12), type IIb
      dyslipidaemic (n = 13), type IV hypertriglyceridaemic (n = 18) and
      normolipidaemic (n = 15) were recruited. A complete lipid profile including
      prebeta-HDL was performed. Cholesterol efflux from Fu5AH cells as well as from
      control or cAMP pretreated J774 cells were measured; the difference between these
      two latter values being taken as the ABCA1-mediated efflux. RESULTS: The Fu5AH
      and the control J774 cells delivered cholesterol to mature HDLs, especially to
      phospholipid (PL)-rich HDL. Using cAMP pretreated cells, the ABCA1-dependent
      efflux was highly sensitive to prebeta-HDL, which appeared to be a factor in
      determining the efflux. Consistent with the dependence of the SR-BI-mediated
      efflux on HDL-PL levels, which are not different between groups, all sera
      displayed similar efflux capacities from the Fu5AH cells. Conversely, in
      accordance with their high prebeta-HDL levels, the ABCA1-dependent efflux
      highlighted the efficiency of type IV sera. CONCLUSION: Two complementary
      cellular models providing SR-BI and ABCA1-dependent efflux should be used to
      measure the capacity of a biological fluid which contains a wide variety of
      components to promote cholesterol efflux.

PMID- 16893378
TI  - Atorvastatin or fenofibrate on post-prandial lipaemia in type 2 diabetic patients
      with hyperlipidaemia.
AB  - BACKGROUND: Post-prandial lipid abnormalities might contribute to the excess of
      cardiovascular risk typical of type 2 diabetic patients. The study evaluated the
      effects of atorvastatin (20 mg d(-1)) vs. fenofibrate (200 mg d(-1)) on post
      prandial lipids in type 2 diabetic patients with mixed hyperlipidaemia. MATERIALS
      AND METHOD: Eight type 2 diabetic patients, male/female (M/F) 6/2, age 58 +/- 5
      years, body mass index (BMI) 28 +/- 3 kg m(-2) with cholesterol of low-density
      lipoprotein (LDL) between 100-160 mg dL(-1) and triglycerides between 150-400 mg
      dL(-1), participated in a randomized, cross-over study (3 months on atorvastatin
      and 3 months on fenofibrate). At baseline and at the end of the two treatments,
      the patients were given a standard fat meal; blood samples were taken before the
      meal and every 2 h after for the assay of cholesterol, triglycerides, apoB-48 and
      apoB-100 (determined by sodium dodecyl sulphate-polyacrylamide gel
      electrophoresis) in plasma lipoproteins and very low-density lipoprotein (VLDL)
      subfractions (large and small VLDL), separated by density gradient
      ultracentrifugation. RESULTS: Data on fasting lipids confirmed that atorvastatin
      was more effective on the reduction of LDL-cholesterol, whereas fenofibrate was a
      better triglyceride-lowering agent. Concerning the post-prandial phase, the
      incremental areas under the curve (IAUC) for chylomicrons and large VLDL were
      reduced after both treatments, reaching statistical significance for cholesterol,
      triglyceride and apoB-100 content of chylomicrons only after fenofibrate
      administration [IAUC, (5.2 +/- 4.6 vs. 10.7 +/- 9.3) mg dL(-1) h(-1), P = 0.03;
      (131.3 +/- 95.1 vs. 259.1 +/- 201.5) mg dL(-1) h(-1), P = 0.02; (0.46 +/- 1 vs. 3
      +/- 3.7) mg dL(-1) h(-1), P = 0.025, all respectively]. CONCLUSIONS: During the
      post-prandial state fenofibrate appeared to be more effective than atorvastatin
      in reducing the chylomicron response.

PMID- 16893380
TI  - Is the pattern of solid-phase gastric emptying different between genders?
AB  - BACKGROUND: In the 13C-octanoate breath test, the shape of the 13CO2 excretion
      curve in the ascending portion reflects a pattern of gastric emptying (GE).
      Recent scintigraphic studies have revealed an overall delay in solid GE in
      fertile women compared with men. However, it remains unknown whether women have a
      different GE pattern compared with men. As a symptomatic delay in solid GE is
      specific to the female gender, it could be hypothesized that the 13CO2 excretion
      curve is different in shape between genders. MATERIALS AND METHODS: Because the
      ascending gradient of the 13CO2 excretion curve is often biphasic, the dual
      function of y(t) = ( a1 . tb1 + a2 . tb2) e(-K.t) was applied to fit the breath
      data, where a1, b1, a2, b2, and K are constants. Assessed on the 4 h-based breath
      samples obtained after ingestion of a 320-kcal muffin containing 100 mg 13C
      octanoate, the time versus 13CO2 excretion curve was created from 31 adult
      volunteers (15 men and 16 women). The curve shape was characterized by the dual
      function, and was compared between genders. RESULTS: In both genders, the
      ascending gradient exhibited the biphasic feature, characterized by an initial
      steep rise and the subsequent blunted increase, while the descending gradient
      followed the monotonous decay. The initial rise was steeper and the subsequent
      increase was more blunted in women than in men. CONCLUSION: Women exhibit a
      gender-specific pattern of the 13CO2 excretion profile. A possible explanation
      for this gender difference is that the post-gastric feedback regulation is more
      potent in women than in men.

PMID- 16893379
TI  - Receptor activator of nuclear factor kappaB ligand and osteoprotegerin in men
      with thyroid cancer.
AB  - BACKGROUND: Suppressive thyroid hormone therapy is generally a lifelong treatment
      for patients with differentiated thyroid cancer (DTC). However, long-standing
      thyrotropin (TSH) suppression is a risk factor for osteoporosis. Osteoprotegerin
      (OPG) and receptor activator of nuclear factor kappaB ligand (RANKL) are central
      regulators of bone turnover. The aim was to analyze the effects of a suppressive
      thyroid hormone therapy in males with DTC on the OPG/RANKL system and on bone
      metabolism. PATIENTS AND METHODS: The OPG and soluble RANKL (sRANKL) were
      determined in 40 men (mean age, 53.2 years) with DTC on suppressive thyroid
      hormone therapy (TSH; 0.053 +/- 0.037 mU L(-1), duration 5.7 +/- 4.4 years) and
      120 healthy controls matched for age. The markers of bone metabolism were C
      terminal telopeptide of type I collagen in serum (sCTx) and osteocalcin (OC).
      RESULTS: The control group had OPG values (mean +/- SD) of 1.9 +/- 1.0 pmol L(-1)
      and sRANKL values of 0.40 +/- 0.62 pmol L(-1). In patients with DTC, results for
      OPG were 3.03 +/- 1.04 pmol L(-1) (P < 0.05) and for sRANKL were 0.13 +/- 0.16
      pmol L(-1) (P < 0.05). The control group presented values for sCTx of 2669 +/-
      1132 pmol L(-1) and for OC of 17.89 +/- 6.5 ng mL(-1). Patients with DTC on
      suppressive thyroid hormone therapy had increased sCTx values of 3810 +/- 2020
      pmol L(-1) (P = 0.03) but comparable OC values of 19.21 +/- 7.67 ng mL(-1) (NS).
      CONCLUSIONS: Suppressive thyroid hormone therapy in men with DTC increased bone
      degradation and induced significant changes in the OPG/RANKL system. These
      changes include, besides the risk of osteoporosis, possible negative effects on
      the vascular function and an increased risk of cardiovascular disease.

PMID- 16893381
TI  - Anti-emetic prophylaxis with oral tropisetron and/or dexamethasone.
AB  - BACKGROUND: The corticosteroid dexamethasone and the serotonine3 -antagonist
      tropisetron are both effective drugs for the prophylaxis of post-operative nausea
      and vomiting (PONV) when given intravenously. The aim of this trial was to
      evaluate the oral use of both drugs as part of a routine oral premedication and
      to compare their single and combined effectiveness. MATERIALS AND METHODS: In
      this randomized, placebo-controlled, double-blind study, 320 inpatients with a
      moderate-high risk of PONV (> or = 40% according to two validated risk scores)
      received an oral premedication 1-2 h pre-operatively with placebo, a fixed dose
      of tropisetron 5 mg, dexamethasone 8 mg, or a combination of both drugs. A
      standardized general anaesthesia was performed, including benzodiazepine
      premedication, propofol, rocuronium, desflurane in air/O2, fentanyl or sufentanil
      followed by a continuous infusion of remifentanil. Post-operative analgesia and
      anti-emetic rescue medication were standardized. The main outcome measures were
      the severity of PONV within the first 24 h (rated by a standardized scoring
      algorithm). The incidence of PONV was used as the secondary outcome. RESULTS:
      Data from 310 patients were analyzed. The mean severity score in the placebo-,
      tropisetron-, dexamethasone- and the combined-groups was 1.37, 0.8, 0.8 and 0.38,
      respectively. The incidence of PONV of any severity was 59.2%, 37.5%, 40% and
      22.8%, respectively. The reduction of the incidence and the severity of PONV were
      statistically significant with all three interventions. Results from additional
      analyses suggested that both drugs were equally effective and that there was a
      simple additive effect of tropisetron and dexamethasone compared with placebo.
      CONCLUSION: Oral tropisetron and dexamethasone were both equally effective in
      reducing the severity and incidence of post-operative nausea and vomiting. The
      latter could be reduced by approximately 35% in a population of moderate-high
      risk for PONV. Both drugs had an additive effect. However, even in the
      combination group there still remained an unacceptably high incidence of PONV of
      more than 20%. This highlighted the need for a multimodal anti-emetic approach in
      high-risk patients and the importance of treatment of PONV.

PMID- 16893382
TI  - Modulation of HER2 expression by ferulic acid on human breast cancer MCF7 cells.
AB  - BACKGROUND: The molecular mechanisms underlying the mitogenic effect of ferulic
      acid (FA), an active compound derived from Angelica sinensis, have never been
      elucidated. It was the aim of this study to investigate the proliferative effect
      of FA on human breast cancer cell lines and to elucidate its modulation mechanism
      on HER2 expression in MCF7 line. MATERIALS AND METHODS: By using MCF7 (oestrogen
      receptor-positive; ER+, HER2-low), BT474 (ER+, HER2-high), MDAMB231 (ER-, HER2
      low) and SKBR3 (ER-, HER2-high) human breast cancer cell lines as in vitro
      models, the mitogenic effects of FA were assessed by trypan blue dye exclusion
      assay and DNA flow cytometry. Ferulic acid-modulated cell signalling and HER2
      gene expression were evaluated in MCF7 line by Western blot and real-time RT-PCR
      analysis. RESULTS: Ferulic acid ER-dependently stimulated cell proliferation on
      MCF7 cells in a concentration-dependent manner. The HER2 oncogene (one of the
      prognostic factors of breast cancer) and ESR1 gene (oestrogen receptor-alpha;
      ERalpha) transcription were markedly up-regulated by FA treatment. Besides, HER2
      signalling and its downstream molecules such as AKT and ERK1/2 were involved in
      FA-modulated ERalpha and cyclin D1 synthesis. Addition of anti-HER2 antibody,
      trastuzumab, abrogated FA-enhanced proliferative effect on MCF7 cells, indicated
      a positive feedback control for the action of HER2 in this setting. The fact that
      the ER antagonist blocked most of the FA-up-regulated HER2 expression, and that
      trastuzumab down-regulated ERalpha gene expression, suggested a cross-talk
      between ERalpha and HER2 signalling on MCF7 cells. CONCLUSION: The authors'
      conclude that FA causes human breast cancer cell proliferation by up-regulation
      of HER2 and ERalpha expression.

PMID- 16893383
TI  - Genetic polymorphisms of adhesion molecules in children with severe RSV
      associated diseases.
AB  - Adhesion molecules are involved in the pathophysiology of respiratory syncytial
      virus (RSV)-associated diseases. By testing polymorphisms within ICAM-1, VCAM-1
      and E-selectin, we found no evidence for association of any polymorphism with
      severe RSV infections. Thus, we conclude that these genes do not predispose to
      severe RSV-associated diseases.

PMID- 16893384
TI  - Protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene R620W variant and
      sporadic idiopathic hypoparathyroidism in Asian Indians.
AB  - Recently, a gain of function variant C1858T of the lymphoid-specific protein
      tyrosine phosphatase non-receptor (LYP, PTPN22) gene has been reported to be
      associated with several autoimmune disorders including Graves' disease, type 1
      diabetes, rheumatoid arthritis and vitiligo. The present study was carried out in
      80 patients with sporadic idiopathic hypoparathyroidism (SIH) [43 males and 37
      females, mean +/- SD age and duration of symptoms 32.5 +/- 14.1 years and 6.7 +/-
      7.2 years (range 1 day to 35 years), respectively] and 193 healthy controls (male
      : female ratio 91:102, mean +/- SD age, 43.1 +/- 11.6 years) to assess
      association of 1858T allele with the disease. Polymerase chain reaction
      restriction fragment length polymorphism analysis was performed to genotype
      C1858T variant. The frequency of occurrence of 1858T allele was 4/160 (2.5%) in
      SIH and 5/386 (1.3%) in the control alleles (odds ratio 1.95, 95% CI 0.51-7.37).
      Thus, the present study reveals that 1858T allele is rare (1.3%) in Asian
      Indians. The trend of higher prevalence of 1858T allele in patients with SIH
      needs to be studied further in other population with higher rate of the allele to
      support the autoimmune basis of the disease.

PMID- 16893386
TI  - A novel HLA-A*0119 allele of a Caucasian family containing a mutation in a highly
      conserved region.
AB  - A novel human leucocyte antigen (HLA)-A (HLA-A*0119) allele has been identified
      in two individuals of a Caucasian family from Middle Europe using a single-allele
      specific sequencing strategy. This allele is identical to the HLA-A*0101 allele
      except for one point mutation in the highly conserved codon 92 (TCT --> GCT)
      resulting in an amino acid change from serine to alanine.

PMID- 16893385
TI  - MICA-STR, HLA-B haplotypic diversity and linkage disequilibrium in the Hunan Han
      population of southern China.
AB  - Major histocompatibility complex (MHC) class I chain-related gene A (MICA) is
      located 46 kb centromeric to HLA-B and encodes a stress-inducible protein. MICA
      allelic variation is thought to be associated with disease susceptibility and
      immune response to transplants. This study was aimed to investigate the
      haplotypic diversity and linkage disequilibrium between human leukocyte antigen
      (HLA)-B and (GCT)(n) short tandem repeat in exon 5 of MICA gene (MICA-STR) in a
      southern Chinese Han population. Fifty-eight randomly selected nuclear families
      with 183 members including 85 unrelated parental samples were collected in Hunan
      province, southern China. HLA-B generic typing was performed by polymerase chain
      reaction-sequence-specific priming (PCR-SSP), and samples showing novel HLA-B
      MICA-STR linkage were further typed for HLA-B allelic variation by high
      resolution PCR-SSP. MICA-STR allelic variation and MICA gene deletion (MICA*Del)
      were detected by fluorescent PCR-size sequencing and PCR-SSP. Haplotype was
      determined through family segregation analysis. Statistical analysis was applied
      to the data of the 85 unrelated parental samples. Nineteen HLA-B specificities
      and seven MICA-STR allelic variants were observed in 85 unrelated parental
      samples, the most predominant of which were HLA-B*46, -B60, -B*13, and -B*15, and
      MICA*A5, MICA*A5.1 and MICA*A4, respectively. Genotype distributions of HLA-B,
      MICA-STR loci were consistent with Hardy-Weinberg proportions. The HLA-B-MICA-STR
      haplotypic phases of all 85 unrelated parental samples were unambiguously
      assigned, which contained 30 kinds of HLA-B, MICA-STR haplotypic combinations,
      nine of them have not been reported in the literature. Significant positive
      linkage disequilibria between certain HLA-B and MICA-STR alleles, including HLA
      B*13 and MICA*A4, HLA-B*38 and MICA*A9, HLA-B*58 and MICA*A9, HLA-B*46 and
      MICA*A5, HLA-B*51 and MICA*A6, HLA-B*52 and MICA*A6, and HLA-B60 and MICA*A5.1,
      were observed. HLA-B*48 was linked to MICA*A5, MICA*A5.1 and MICA*Del. HLA-B*5801
      MICA*A10 linkage was found in a family. Our data indicated a high degree of
      haplotypic diversity and strong linkage disequilibrium between MICA-STR and HLA-B
      in a southern Chinese Han population, the data will inform future studies on
      anthropology, donor-recipient HLA matching in clinical transplantation and HLA
      linked disease association.

PMID- 16893387
TI  - Analysis of HLA-DQB1 gene polymorphisms in asymptomatic HBV carriers and chronic
      hepatitis B patients in the Chinese Han population.
AB  - Host genetic factors and environment factors including hepatitis B virus (HBV)
      genotype are widely viewed as common basis of the different outcomes of HBV
      infection. Human leucocyte antigen (HLA) plays an important role in immunological
      reaction to HBV infection. The study aimed to explore whether the HLA-DQB1 allele
      polymorphisms are associated with the outcomes of HBV infection in the Chinese
      Han population. One hundred and thirty-four asymptomatic HBV carriers and 139
      chronic hepatitis B patients were recruited in this case-control study in
      Beijing, China. Sequence-specific primers-polymerase chain reaction was used to
      detect 13 alleles of HLA-DQB1 gene. The frequency distributions of alleles in two
      groups were analysed using sas 9.1.2 software. After adjustment of confounders
      the frequencies of HLA-DQB1*0503 allele and *0303 allele in chronic hepatitis B
      group were statistically significant lower than those in asymptomatic HBV carrier
      group (P = 0.04; P = 0.05), and the frequency of exposure to alcohol consumption
      in patients with chronic hepatitis B was clearly higher than that in asymptomatic
      HBV carrier group (P = 0.004). HLA-DQB1*0503 allele and *0303 allele are
      independently resistant genetic factors to chronic hepatitis B, and alcohol
      consumption is the risk factor of chronic hepatitis B.

PMID- 16893388
TI  - A645G (Lys216Glu) polymorphism of the bactericidal/permeability-increasing
      protein gene in periodontal disease.
AB  - Bactericidal/permeability-increasing protein (BPI) is a member of the pattern
      recognition receptors of the innate immune system and recognizes
      lipopolysaccharides (LPS), a bacterial component belonging to the pathogen
      associated molecular patterns (PAMPs). BPI mediates the neutralization of LPS and
      increases the phagocytosis and cytotoxicity against bacteria. Recently, the
      functionally effective polymorphism A645G resulting in the amino acid alteration
      Lys216Glu has been described. The aim of the study was to investigate the
      association of the A645G polymorphism with chronic periodontal disease. The study
      population comprised 123 patients with periodontal disease (36 with mild, 52 with
      moderate and 35 with severe periodontitis) and 122 healthy, unrelated control
      individuals. Genotyping of the BPI gene polymorphism A645G (Lys216Glu) was
      performed by polymerase chain reaction and restriction fragment length
      polymorphism analysis. Statistical analysis was carried out employing the chi(2)
      test with Yates correction. Genotype and allele frequencies of the polymorphism
      tested herein showed no significant differences between periodontal disease as
      compared to the control group. The frequencies of the G allele were 52.4% in
      patients with periodontal disease and 49.2% in the control individuals (P =
      0.528). Moreover, no significant associations could be detected after
      stratification for disease severity and according to gender. The present study
      does not give evidence for the contribution of the BPI gene to the genetic
      background of chronic periodontal disease.

PMID- 16893389
TI  - Distribution of 22 cytokine gene polymorphisms in the healthy Czech population.
AB  - Cytokine gene polymorphisms (CGP) have been implicated in the pathogenesis of
      immune-mediated diseases including transplant complications via their effect on
      cytokine production and regulation. This study aimed to determine population
      frequencies of selected cytokine single nucleotide polymorphisms in the healthy
      Czech population and compare them with the data from other selected European
      populations. CGP were genotyped by polymerase chain reaction with sequence
      specific primers (PCR-SSP) using the Heidelberg kit in 120 unrelated Czech
      healthy individuals. Chi-squared analysis was used to test for a deviation from
      Hardy-Weinberg equilibrium. Allelic and genotype frequencies and carriage rates
      were determined for 22 CGP located within 13 cytokine genes in total. The
      frequencies observed in this study were similar to those available from the other
      two geographically close Central European centres, but they differed for several
      CGP from the data reported in south European populations. The data on the
      distribution of 22 CGP in the healthy Czech population reported here may be
      utilized to investigate possible associations of CGP with diseases or
      transplantation outcome.

PMID- 16893390
TI  - A chromosomal event resulting in possession and expression of multiple HLA-B and
      Cw genes in a renal patient.
AB  - Routine HLA typing of a renal patient for purposes of registration for
      transplantation revealed an unusual human leucocyte antigen (HLA)-B and Cw
      genotype, with three specificities detected. Results were confirmed in a second
      sample, and in a second laboratory. The possibility of these results reflecting a
      chimaeric state was rejected following short tandem repeat (STR) analysis.
      Although cytogenetic analysis has failed to detect a chromosomal abnormality,
      these findings support the view that the aberrant expression of HLA in this
      patient resulted from an unequal crossover event, occurring during meiosis in a
      previous generation.

PMID- 16893391
TI  - DRB3.2 gene polymorphism and its association with pashmina production in
      Changthangi goat.
AB  - PstI and TaqI restriction fragment length polymorphism (RFLP) of caprine DRB3.2
      revealed three genotypes under each RFLP in Changthangi goat. The genotypic and
      allelic frequency in PstI RFLP was calculated as 0.07, 0.72 and 0.20 for PP, Pp
      and pp genotypes and 0.43 and 0.57 for P and p alleles. In TaqI RFLP the
      frequencies were observed as 0.11, 0.61 and 0.27 for TT, Tt and tt genotypes and
      0.41, 0.59 for T and t alleles. Alignment study indicates variability of
      nucleotides and amino acids between alleles and different breeds of goats. The
      nucleotide sequences reported in this paper have been submitted to the European
      Molecular Biology Laboratory GenBank and the accession numbers were AY496935,
      AY496061 and AY496062. A significant affect (P <or= 0.05) of MHC DRB3.2 PstI
      polymorphism was found on the first and second year of pashmina production.

PMID- 16893392
TI  - The FCGR2A--Arg131 variant is no major mortality factor in the elderly--evidence
      from a German centenarian study.
AB  - The functional single nucleotide polymorphism rs1801274 in the FCGR2A gene
      (His131Arg) influences the efficiency of hIgG2 binding, the main isotype produced
      in response to encapsulated bacteria like Streptococcus pneumoniae and
      Haemophilus influenzae. In contrast to the receptor with the His131 allele,
      FcgammaRIIa-Arg131 binds hIgG2 poorly and carriers of this variant have been
      shown to be much more susceptible to succumb to bacterial pneumonia or
      meningitis. As bacteraemic pneumonia is one of the leading causes of death in
      elderly individuals, we hypothesized that the Arg131 variant could be a major
      mortality factor in the old. We analysed the FCGR2A-His131Arg polymorphism in a
      group of 408 German centenarians and two samples of younger Germans aged 60-75
      and 18-49 years, respectively. No statistically significant differences were
      observed between the three age groups, neither at the allele nor at the genotype
      level. Apparently, the ability to reach old age is largely unaffected by the
      genetically determined efficacy of the FCGR2A-based immune response. However, the
      severely reduced ability of FCGR2A-131Arg carriers to eliminate encapsulated
      bacteria must apparently be compensated by an alternative mechanism, possibly
      involving other genetic survival factors.

PMID- 16893393
TI  - The common -318C/T polymorphism in the promoter region of CTLA4 gene is
      associated with reduced risk of ophthalmopathy in Chinese Graves' patients.
AB  - Studies in the past have clearly established that CTLA4 is a susceptible gene for
      Graves' disease (GD). However, association studies between CTLA4 and the risk of
      developing Graves' ophthalmopathy (GO) in GD patients have shown conflicting
      results. In this study, associations of five CTLA4 single nucleotide
      polymorphisms (-1722A/G, -1661A/G, -318C/T, +49G/A, CT60) with GD risk and GO
      susceptibility in GD patients were investigated in a Chinese population. Our
      results showed that either +49A/G or CT60 polymorphism was associated with GD
      susceptibility in the Chinese population. Significant differences in the
      distribution of the genotypes or alleles evaluated between GD patients with and
      without clinically evident GO were only found for -318C/T polymorphism (P =
      0.03). Multiple logistic regressions revealed that the -318T allele was
      negatively associated with GO under both additive and dominant genetic models
      (adjusted OR = 0.56, 95%CI 0.35-0.89, P = 0.014; adjusted OR = 0.51, 95%CI 0.30
      0.84, P = 0.009, respectively). Stratification analysis according to gender
      demonstrated different scenarios concerning the role of the -318T allele in GO
      risk: a significant protective role for GO was only confirmed in male but not in
      female GD patients. Haplotype analyses showed that only the haplotypes containing
      the -318T allele played a protective role in GO. In conclusion, results from this
      study suggested that the -318T allele might play a protective role in GO
      susceptibility for GD patients at least in the Chinese population. However,
      extended analyses with larger sample size should be carried out in patients from
      different ethnic origins to further verify this association.

PMID- 16893394
TI  - SiPep: a system for the prediction of tissue-specific minor histocompatibility
      antigens.
AB  - Approximately 50 years ago it was found that inbred strains of mice were able to
      reject tumours and skin grafts from major histocompatibility complex (MHC)
      identical donors. They proposed that additional transplantation antigens must
      exist outside the MHC. These were described as minor histocompatibility antigens
      (mHAgs). Since then, related studies in humans have identified 16 human mHAgs.
      The aim of this work is to increase the number of known mHAgs by prediction of
      candidate minor histocompatibility loci by identifying coding single nucleotide
      polymorphisms (SNPs) where the amino acid variation lies within an MHC-binding
      peptide and alters the ability of that peptide to bind. We have developed an
      algorithm called SiPep which uses peptide sequences derived from the flanking
      regions of known non-synonymous SNPs, various MHC-binding and proteolytic
      cleavage evaluation methods and protein expression data to predict mHAgs. We have
      processed 45094 SNPs using the SiPep algorithm and have stored the results in a
      database called SNPBinder. The facilities to process submitted proteins through
      the SiPep algorithm as well as the SNPBinder database are available to the
      public. A set of peptides that are predicted as possible mHAgs by the SiPep
      algorithm have been tested using refolding assays and gel filtration and the
      results are presented in this paper. The SiPep tools and SNPBinder database are
      available free of charge via the internet. An HTML interface providing search
      facilities can be found at the following address: http://www.sipep.org/.

PMID- 16893395
TI  - Cytokine profiling of pulmonary aspergillosis.
AB  - Aspergillus fumigatus is ubiquitous and yet causes invasive, chronic and allergic
      disease of the lung. Chronic cavitary pulmonary aspergillosis (CCPA) is a slowly
      destructive form of pulmonary aspergillosis, without immunocompromise. We
      hypothesized that CCPA cytokine gene polymorphisms would differ from patients
      with allergic bronchopulmonary aspergillosis (ABPA) and uninfected controls. We
      have profiled functional cytokine gene polymorphisms for interleukin (IL)-10, IL
      15, transforming growth factors (TGF)-beta1, tumour necrosis factor (TNF)-alpha
      and interferon (IFN)-gamma in patients with CCPA (n = 24) who were compared with
      other forms of aspergillosis (mostly ABPA) (n = 15) and with ethnically matched
      controls (n = 65-330). Results are described with reference to the high-producing
      genotype in each case. Susceptibility to aspergillosis (all patients compared
      with normal controls) was associated with higher frequency of the IL-15 +13689*A
      allele (OR = 2.37, P = 0.0028) and A/A genotype (chi(2) = 10.31, P < 0.001), with
      a lower frequency of the TNF-alpha-308*A/A genotype (chi(2) = 11.05, P < 0.01).
      Within the aspergillosis patients, CCPA is associated with lower frequency of the
      IL-10 -1082*G allele (OR = 0.38, P = 0.0006) and G/G genotype (chi(2) = 22.45, P
      < 0.001) and with a lower frequency of the TGF-beta1 +869 *T allele (OR +0.42, P
      < 0.0029) and T/T genotype (chi(2) = 17.82, P < 0.001) compared with non-CCPA
      patients and normal controls. Patients infected with Aspergillus appear to be
      higher producers of IL-15, a Th2-promoting cytokine, and lower producers of TNF
      alpha, a cytokine central in protective responses. CCPA occurs in patients who
      are genetically lower producers of both IL-10 and TGF-beta1. As these cytokines
      are regulatory and anti-inflammatory, CCPA may be a consequence of poor
      inflammatory response control in the lung.

PMID- 16893396
TI  - Lack of association between ADAM33 gene and asthma in a Chinese population.
AB  - Asthma is a complex polygenic disease with gene-environment interactions being
      important. It has been previously suggested that ADAM33, which is a member of a
      gene family that encodes membrane-anchored proteins with a disintegrin and a
      metalloprotease domain, is primarily expressed in lung fibroblasts and bronchial
      smooth muscle cells and has been associated with airway remodelling and bronchial
      hyperresponsiveness. A significant association has previously been demonstrated
      between single nucleotide polymorphisms (SNPs) and haplotypes of the ADAM33 and
      asthma in ethnically diverse populations. To assess whether SNPs or haplotypes of
      ADAM33 are related to asthma in a Chinese Han population, we genotyped three SNPs
      of ADAM33 (7575G/A in intron 6, 11188A/T in intron 19, and 12433T/C in exon 20)
      in a case-control study involving 296 patients with asthma and 270 healthy
      controls. No significant association was detected between these three SNPs and
      asthma susceptibility in the Chinese population.

PMID- 16893397
TI  - A functional variant in the CARD4 gene and risk of premature coronary heart
      disease.
AB  - Infection and innate immunity have been suggested as playing an important role in
      the pathogenesis of atherosclerosis. The recently discovered pattern-recognition
      receptor (PRR) proteins initiate signalling after host-pathogen interactions and
      several PRRs, especially the Toll-like receptor 4 (TLR4), have been shown to be
      involved in the development and progression of atherosclerosis. A new addition to
      the PRRs is CARD4, a gene that encodes the protein nucleotide-binding
      oligomerization domain 1 (NOD1) and that seems to be associated with barrier
      function in chronic inflammatory disorders. Recently, a functional variant in the
      CARD4 gene, the insertion-deletion polymorphism ND(1)+32656, has been associated
      with inflammatory barrier diseases (inflammatory bowel diseases and asthma). We
      analysed the frequencies of this known functional mutation in the CARD4 gene and
      of the two adjacent variants, rs2075822 and rs2907748, in a German sample of 1440
      unrelated early onset coronary heart disease (CHD) patients and healthy controls.
      Genotype and haplotype data showed no evidence for a significant association of
      these CARD4 variants with CHD. Our results suggest that the analysed CARD4
      mutations do not play a major role in the aetiology of CHD.

PMID- 16893399
TI  - Changes in the scrotal temperature of subjects in a sedentary posture over a
      heated floor.
AB  - As Koreans habitually sit on the heated floor in their residential buildings, the
      male testis is directly exposed, and is therefore affected by the floor surface
      temperature. The purpose of this study was to investigate the changes in the
      scrotal temperature of the subjects in a sedentary posture over the heated floor.
      A rigid screening test was performed to select healthy subjects. Finally, six
      college students volunteered to participate in the experiments. Two experiments
      were performed in a controlled environmental chamber. Experiment I was designed
      for a low metabolism state, with the subjects reading a book in a sedentary
      posture for 50 min. The floor surface temperature (tf) was controlled by varying
      the temperature of water (tw) flowing into the floor coil from 15 to 50 degrees
      C, at 5 degrees C intervals. Experiment I revealed that the final scrotal surface
      temperature was 32.27, 32.62, 33.51, 33.34, 34.14, 34.28, 34.34 and 35.04 degrees
      C at the tw 15 degrees C (tf 17.0 degrees C), 20 degrees C (tf 20.8 degrees C),
      25 degrees C (tf 24.1 degrees C), 30 degrees C (tf 27.8 degrees C), 35 degrees C
      (tf 31.7 degrees C), 40 degrees C (tf 35.9 degrees C), 45 degrees C (tf 38.6
      degrees C) and 50 degrees C (tf 42.2 degrees C), respectively. At tf 17.0 and
      20.8 degrees C, the scrotal temperature exhibited a declining pattern and a low
      temperature for spermatogenesis. At tf 24.1, 27.8 and 31.7 degrees C, however,
      the thermal regulatory system of the scrotum and testis was activated
      appropriately. On the contrary, scrotal temperature ascended at tf 35.9, 38.6 and
      42.2 degrees C. Of the six subjects, two subjects demonstrated scrotal
      temperatures above 35 degrees C at tf 38.6 degrees C and four subjects exhibited
      scrotal temperatures above 35 degrees C at tf 42.2 degrees C. Experiment II was
      designed for a high metabolism state, with the subjects playing a card game in a
      sedentary posture for 180 min. The tf was controlled by varying the tw from 30 to
      40 degrees C, at 5 degrees C intervals. Experiment II revealed that the final
      scrotal temperature was 33.43, 34.78 and 35.61 degrees C, and the difference
      between the initial and final scrotal temperatures was +0.34, +1.06 and +2.24
      degrees C, at tw 30 degrees C (tf 27.8 degrees C), 35 degrees C (tf 31.7 degrees
      C) and tw 40 degrees C (tf 35.9 degrees C), respectively. The scrotal temperature
      was affected by the floor surface temperature and by the rate of metabolism of
      the subject in a sedentary posture. As derived from regression analysis, the
      recommended surface temperature of a heated floor is within 23-33 degrees C under
      the assumption that scrotal and consecutively testicular temperature above 35
      degrees C impairs spermatogenesis.

PMID- 16893402
TI  - Anemia management in chronic kidney disease: what have we learned after 17 years?
AB  - Anemia management remains controversial in patients with chronic kidney disease
      (CKD). The overwhelming conclusion from retrospective data analyses show a strong
      correlation between higher hemoglobin values and improved outcomes, including
      mortality, hospitalization, left ventricular hypertrophy, and quality of life.
      However, the evidence available from two large prospective trials in CKD
      comparing hemoglobin values near the current target of 11-12 g/dl with
      normalization or near normalization were stopped, as there was a trend toward
      worsening outcomes in the higher hemoglobin groups. This disparity suggests that
      patients who have or achieve high hemoglobin values on low doses or no
      erythropoietin may be inherently different from the general CKD population.
      Therefore targeting to a hemoglobin value above the current recommendation with
      intermittent erythropoietin seems unwarranted until randomized prospective trials
      demonstrate both safety and efficacy.

PMID- 16893400
TI  - Penile duplex pharmaco-ultrasonography of cavernous arteries in men with erectile
      dysfunction and generalized atherosclerosis.
AB  - Assessment of cavernosal perfusion in men with erectile dysfunction (ED) relies
      on Doppler spectrum analysis of pharmachologically stimulated peak systolic
      velocity (sPSV) in cavernous arteries but its accuracy in identifying men
      affected by a cavernosal perfusion disorder correlated with atherosclerosis
      remains undefined. We estimated by B-mode ultrasound, the accuracy of sPSV of
      cavernous arteries to identify ED with an expected cavernosal perfusion disorder.
      This was predicted by an elevated intima-media thickness (IMT) of common carotid
      arteries, a reference methodology to estimate the degree of generalized
      atherosclerosis, in men exposed to vascular risk factors (VRFs). sPSV and IMT
      were evaluated in 269 men with ED, 49 had no VRFs, 100 were overweight with/or
      without hyperlipidaemia, 120 were affected by type 2 diabetes and/or essential
      hypertension. sPSV was significantly lower (p<0.05) in patients with VRFs
      associated with atherosclerosis (IMT>or=1 mm) (n=39) than in men with no VRFs and
      no atherosclerosis (n=49). sPSV correlated negatively with age (p<0.0001), with
      serum% of glycated haemoglobin (p=0.010) and with carotid artery IMT (p=0.013).
      An sPSV<or=30 cm/sec, the cut-off value which showed at receiver operating
      characteristic curve analysis the combined highest value of sensitivity and
      specificity, correctly identified only 57% of men in whom a cavernosal perfusion
      disorder was expected based on the presence of carotid artery IMT>or=1 mm
      combined to the exposure to VRFs. The ultrasonographic evaluation of sPSV had a
      very limited accuracy in discriminating ED with an expected cavernosal perfusion
      disorder, based on the presence of a generalized atherosclerosis in men with
      VRFs.

PMID- 16893403
TI  - Erythropoietin resistance in the treatment of the anemia of chronic renal
      failure.
AB  - Resistance to erythropoietin therapy is a common complication of the modern
      management of anemia in chronic kidney disease. Iron deficiency, deficiency of
      other nutrients, toxins, infections, and inadequate dialysis account for the vast
      majority of episodes of such resistance.

PMID- 16893404
TI  - Nonhematologic complications of erythropoietin therapy.
AB  - Exogenous recombinant human erythropoietin (rHuEPO) is a beneficial therapeutic
      agent for correction of anemia in both chronic kidney disease (CKD) and end-stage
      renal disease (ESRD) patients. Transfusion requirements in ESRD patients are
      reduced significantly and anemia management is much improved. Despite widespread
      use and near-universal exposure of ESRD patients to the drug, rHuEPO remains an
      effective and safe product. However, a number of nonhematologic complications are
      described with rHuEPO therapy. Most notable is hypertension, whereas the
      connection between seizure and enhanced thrombosis is less clear. A possible
      complication recently described is exacerbation of proliferative diabetic
      retinopathy. Finally, other less common adverse effects, although rare in most
      patients, should be recognized as such by physicians who prescribe rHuEPO.

PMID- 16893405
TI  - Intravenous iron therapy in end-stage renal disease.
AB  - Intravenous iron therapy is instrumental in the management of anemia in patients
      with end-stage renal disease (ESRD). Iron is available in several different
      preparations, with slight differences in the pharmacology of each. Given the
      importance of intravenous iron in the management of these patients, clinicians
      should be aware of the potential risks associated with it. Intravenous iron has
      effects on host immunity that raise concerns about clinical infection risk. Iron
      preparations appear to increase oxidative stress in these patients, which has
      important implications for cardiovascular disease states. Lastly, the effects of
      intravenous iron on liver disease are largely unknown.

PMID- 16893406
TI  - Neutrophil dysfunction and infection risk in end-stage renal disease.
AB  - Infections are still a major cause of morbidity and mortality in end-stage renal
      disease (ESRD) patients. The susceptibility of ESRD patients to infections is
      typically ascribed to the immunodeficient state associated with uremia. A central
      role in the host defense against bacterial infections is played by phagocytic
      polymorphonuclear white blood cells, which are characterized by the capacity to
      ingest and subsequently destroy bacteria. Disorders in polymorphonuclear cell
      function are exacerbated by the dialysis procedure and numerous factors including
      uremic toxins, iron overload, anemia of renal disease, and dialyzer
      bioincompatibility. It is concluded that the phagocytic defect observed in ESRD
      is multifactorial, and each factor should be managed individually with specific
      therapeutic approaches.

PMID- 16893407
TI  - When heparin causes thrombosis: significance, recognition, and management of
      heparin-induced thrombocytopenia in dialysis patients.
AB  - Heparin-induced thrombocytopenia (HIT) is characterized by thrombocytopenia and
      paradoxical hypercoagulability. HIT occurs when an antibody ("HIT antibody")
      produced against the complex of heparin and platelet factor 4 (PF4) causes
      systemic platelet consumption and activation. Nephrologists encounter HIT in the
      care of end-stage renal disease (ESRD) patients because heparin is a routine
      anticoagulant in hemodialysis. The incidence of HIT in ESRD appears to be lower
      than in other clinical settings. However, HIT is equally life threatening in ESRD
      patients and therefore demands the same prompt recognition and aggressive
      treatment. Diagnosing HIT requires the detection of HIT antibodies. A functional
      assay (e.g., [(14)C] serotonin release assay) relies on the patient's HIT
      antibodies to activate donor platelets at pharmacologic heparin concentrations.
      The more common antigen assay (e.g., enzyme-linked immunosorbent assay [ELISA])
      detects the binding of the patient's HIT antibodies to antigens (e.g., heparin
      PF4 complex) in a microtiter well and does not involve platelets. The moment HIT
      is suspected, heparin should be stopped and an alternative anticoagulant
      initiated immediately, even before the result of a serologic test becomes
      available. The advent of several new anticoagulants in the last decade,
      especially argatroban and bivalirudin, has expanded treatment options for HIT in
      dialysis patients. This review discusses the epidemiology, pathogenesis, clinical
      features, diagnosis, and treatment of HIT, with special emphasis on concepts
      relevant to the care of dialysis patients.

PMID- 16893408
TI  - The safety of heparins in end-stage renal disease.
AB  - In patients on chronic dialysis, unfractionated heparin (UFH) is the most
      commonly used agent for anticoagulation of the hemodialysis extracorporeal
      circuit, for hemodialysis catheter "locking" between dialysis treatments, and for
      nondialysis indications such as venous thromboembolic disease, peripheral
      vascular disease, and acute coronary artery disease. Potentially serious
      complications of UFH, such as hemorrhage, osteoporosis, and thrombocytopenia,
      have led to consideration of other options for anticoagulation, including low
      molecular weight heparin (LMWH) and direct thrombin inhibitors (DTIs). LMWH can
      be used for anticoagulation of the hemodialysis circuit, but whether this has
      significant benefit compared to UFH remains to be proven. Because of the somewhat
      unpredictable risk of severe bleeding complications when LMWH is used for other
      indications in dialysis patients, UFH rather than LMWH is preferred for treatment
      of thromboembolic disease in these patients. DTIs have been used for
      anticoagulation in dialysis patients with heparin-induced thrombocytopenia (HIT),
      with argatroban being the preferred agent if heparin-free hemodialysis cannot be
      performed. UFH still remains the preferred anticoagulant in the vast majority of
      dialysis patients requiring systemic anticoagulation and for anticoagulation of
      the extracorporeal hemodialysis circuit.

PMID- 16893409
TI  - Anticoagulation and continuous renal replacement therapy.
AB  - More than half of patients with acute renal failure in the intensive care unit
      require dialysis, and the majority of them have significant hemodynamic
      instability. Continuous renal replacement therapy (CRRT) is often the preferred
      dialysis modality in these patients. One requirement for CRRT is anticoagulation,
      which can expose patients to the risk of bleeding. However, absence of effective
      anticoagulation may result in clotting of the CRRT circuit and subsequently less
      effective treatment. While heparins are widely used for anticoagulation, because
      of potential side effects such as bleeding and heparin-induced thrombocytopenia,
      alternative anticoagulation protocols should be considered. Citrate
      anticoagulation, regional heparin/protamine, predilution, r-hirudin,
      prostacyclin, and nafamostat are among these methods.

PMID- 16893410
TI  - Platelet dysfunction and end-stage renal disease.
AB  - Patients with end-stage renal disease (ESRD) develop hemostatic disorders mainly
      in the form of bleeding diatheses. Hemorrhage can occur at cutaneous, mucosal, or
      serosal sites. Retroperitoneal or intracranial hemorrhages also occur. Platelet
      dysfunction is the main factor responsible for hemorrhagic tendencies in advanced
      kidney disease. Anemia, dialysis, the accumulation of medications due to poor
      clearance, and anticoagulation used during dialysis have some role in causing
      impaired hemostasis in ESRD patients. Platelet dysfunction occurs both as a
      result of intrinsic platelet abnormalities and impaired platelet-vessel wall
      interaction. The normal platelet response to vessel wall injury with platelet
      activation, recruitment, adhesion, and aggregation is defective in advanced renal
      failure. Dialysis may partially correct these defects, but cannot totally
      eliminate them. The hemodialysis process itself may in fact contribute to
      bleeding. Hemodialysis is also associated with thrombosis as a result of chronic
      platelet activation due to contact with artificial surfaces during dialysis.
      Desmopressin acetate and conjugated estrogen are treatment modalities that can be
      used for uremic bleeding. Achieving a hematocrit of 30% improves bleeding time in
      ESRD patients.

PMID- 16893411
TI  - Dialysis-related carnitine disorder.
AB  - L-carnitine plays an essential role in the beta-oxidation of fatty acids by
      catalyzing their transport into the mitochondrial matrix. The kidney maintains
      plasma free L-carnitine levels in the homeostatic range by selective saturable
      tubular reabsorption. The preferential retention of free L-carnitine over acyl-L
      carnitines by the kidney is lost in patients with end-stage renal disease (ESRD).
      Loss of renal parenchyma as a site of carnitine synthesis, as well as
      nonselective clearance of L-carnitine by the dialysis procedure lead to dialysis
      related carnitine deficiency. Numerous studies investigating whether L-carnitine
      supplementation will alleviate several dialysis-related symptoms, such as
      intradialytic hypotension, heart failure, muscle weakness, low exercise capacity,
      and anemia, have reported conflicting results. Many of these studies suffer from
      a lack of randomization and control groups, heterogeneity in the administration
      of L-carnitine, and nonstandardized measures of symptom improvement. More data
      exist to support the use of L-carnitine in selected anemic dialysis patients with
      very large erythropoietin requirements in whom extensive examination for
      reversible causes of anemia was unrevealing.

PMID- 16893412
TI  - Multiple myeloma in end-stage renal disease.
AB  - Multiple myeloma is a common cause of chronic kidney disease (CKD). Patients with
      myeloma-related kidney disease but low levels of serum monoclonal proteins can be
      diagnosed with symptomatic myeloma in a simplified diagnostic classification. The
      presence and type of renal disease in myeloma is dependent on the light chain
      secreted. Treatment has recently changed and now includes the use of thalidomide
      and bisphosphonates. Thalidomide can cause hyperkalemia and bisphosphonates can
      cause renal failure in patients with CKD. Their use is not contraindicated, but
      they should be used with caution. High-dose melphalan with an autologous stem
      cell transplant is now the standard of care and should not be withheld from
      patients with CKD, even those on dialysis. This treatment can improve the renal
      disease, and this is more likely if treatment is started early. In patients with
      persistent dialysis dependence, renal transplantation can be performed if the
      patient has a complete remission.

PMID- 16893414
TI  - Does the p75 neurotrophin receptor mediate Abeta-induced toxicity in Alzheimer's
      disease?
AB  - Alzheimer's disease is characterized by the over-production and accumulation of
      amyloidogenic Abeta peptide, which can induce cell death in vitro. It has been
      suggested that the death signal could be transduced by the pan neurotrophin
      receptor (p75NTR). p75NTR is well known for its ability to mediate neuronal death
      in neurodegenerative conditions and is inextricably linked with changes that
      occur in Alzheimer's disease. Moreover, Abeta binds to p75NTR, activating
      signalling cascades. However, the complexity of p75NTR-mediated signalling, which
      does not always promote cell death, leaves open the possibly of Abeta promoting
      death via an alternative signalling pathway or the regulation of other p75NTR
      mediated actions. This review focuses on the interactions between Abeta and
      p75NTR in the context of the broader p75NTR signalling field, and offers
      alternative explanations for how p75NTR might contribute to the aetiology of
      Alzheimer's disease.

PMID- 16893413
TI  - Vascular access thrombosis prophylaxis.
AB  - Vascular access thrombosis in the hemodialysis patient leads to significant cost
      and morbidity. Fistula patency supersedes graft patency, therefore obtaining a
      mature functioning fistula in patients approaching end-stage renal disease (ESRD)
      by early patient education and referral needs to be practiced. Current methods to
      maintain vascular access patency rely on early detection and radiologic or
      surgical prevention of thrombosis. Study of thrombosis biology has elucidated
      other potential targets for the prophylaxis of vascular access thrombosis. The
      goal of this review is to examine the current available methods for vascular
      access thrombosis prophylaxis.

PMID- 16893415
TI  - Neurotrophin-induced preprotachykinin-A gene promoter modulation in organotypic
      rat spinal cord culture.
AB  - To study regulation of the preprotachykinin-A gene promoter, we utilised a
      biolistic gene transfer protocol to deliver a DNA construct that incorporates a
      portion of the preprotachykinin-A gene promoter and an enhanced green fluorescent
      protein reporter gene into neonatal rat spinal cord organotypic slices. The
      ability of the neurokinin-1 receptor agonist [Sar9,Met(O2)11]-substance P, nerve
      growth factor and brain derived neurotrophic factor to modulate positively
      preprotachykinin-A gene promoter construct activity, as indicated by de novo
      enhanced green fluorescent protein expression, was determined. Treatment of
      organotypic slices with [Sar9, Met(O2)11]-substance P (10 microm, P < 0.05),
      nerve growth factor (200 ng/mL, P < 0.001) or brain derived neurotrophic factor
      (200 ng/mL, P < 0.02) significantly increased the proportion of cytomegaloviral
      promoter-DsRed transfected cells (used to visualise total transfected cells) that
      co-expressed enhanced green fluorescent protein. The distribution of enhanced
      green fluorescent protein/DsRed-positive neurones across spinal laminae was
      broadly in line with the known distribution of spinal Trk and neurokinin-1
      receptors. These data suggest a modulated activity of the preprotachykinin-A gene
      promoter in spinal neurones in vitro by substance P and/or neurotrophins. The
      functional consequences of such transcriptional changes within central
      peptidergic circuitry and their relevance to chronic pain are considered.

PMID- 16893416
TI  - Extensive degradation of myelin basic protein isoforms by calpain following
      traumatic brain injury.
AB  - Axonal injury is one of the key features of traumatic brain injury (TBI), yet
      little is known about the integrity of the myelin sheath. We report that the 21.5
      and 18.5-kDa myelin basic protein (MBP) isoforms degrade into N-terminal
      fragments (of 10 and 8 kDa) in the ipsilateral hippocampus and cortex between 2 h
      and 3 days after controlled cortical impact (in a rat model of TBI), but exhibit
      no degradation contralaterally. Using N-terminal microsequencing and mass
      spectrometry, we identified a novel in vivo MBP cleavage site between Phe114 and
      Lys115. A MBP C-terminal fragment-specific antibody was then raised and shown to
      specifically detect MBP fragments in affected brain regions following TBI. In
      vitro naive brain lysate and purified MBP digestion showed that MBP is sensitive
      to calpain, producing the characteristic MBP fragments observed in TBI. We
      hypothesize that TBI-mediated axonal injury causes secondary structural damage to
      the adjacent myelin membrane, instigating MBP degradation. This could initiate
      myelin sheath instability and demyelination, which might further promote axonal
      vulnerability.

PMID- 16893417
TI  - Phosphorylation of dystrophin Dp71d by Ca2+/calmodulin-dependent protein kinase
      II modulates the Dp71d nuclear localization in PC12 cells.
AB  - We have shown that the splicing isoform of Dp71 (Dp71d) localizes to the nucleus
      of PC12 cells, an established cell line derived from a rat pheochromocytoma;
      however, the mechanisms governing its nuclear localization are unknown. As
      protein phosphorylation modulates the nuclear import of proteins, and as Dp71d
      presents several potential sites for phosphorylation, we analyzed whether Dp71d
      is phosphorylated in PC12 cells and the role of phosphorylation on its nuclear
      localization. We demonstrated that Dp71d is phosphorylated under basal conditions
      at serine and threonine residues by endogenous protein kinases. Dp71d
      phosphorylation was activated by 2-O-tetradecanoyl phorbol 13-acetate (TPA), but
      this effect was blocked by EGTA. Supporting the role of intracellular calcium on
      Dp71d phosphorylation, we observed that the stimulation of calcium influx by cell
      depolarization increased Dp71d phosphorylation, and that the calcium-calmodulin
      inhibitor N-(6-aminohexyl)-1-naphthalenesulfonamide (W-7) blocked such induction.
      The blocking action of bisindolylmaleimide I (Bis I), a specific inhibitor for
      Ca2+/diacylglicerol-dependent protein kinase (PKC), on Dp71d phosphorylation
      suggested the participation of PKC in this event. In addition, transfection
      experiments with Ca2+/calmodulin-dependent protein kinase II (CaMKII) expression
      vectors as well as the use of KN-62, a CaMKII-specific inhibitor, demonstrated
      that CaMKII is also involved in Dp71d phosphorylation. Stimulation of Dp71d
      phosphorylation by cell depolarization and/or the overexpression of CaMKII
      favored the Dp71d nuclear accumulation. Overall, our results indicate that CAMKII
      mediated Dp71d phosphorylation modulates its nuclear localization.

PMID- 16893419
TI  - GATA-3 regulates the transcriptional activity of tyrosine hydroxylase by
      interacting with CREB.
AB  - The zinc finger transcription factor GATA-3 is a master regulator of type 2 T
      helper cell development. Interestingly, in GATA-3-/- mice, noradrenaline (NA)
      deficiency is a proximal cause of embryonic lethality. However, neither the role
      of GATA-3 nor its target gene(s) in the nervous system were known. Here, we
      report that forced expression of GATA-3 resulted in an increased number of
      tyrosine hydroxylase (TH) expressing neurons in primary neural crest stem cell
      (NCSC) culture. We also found that GATA-3 transactivates the promoter function of
      TH via specific upstream sequences, a domain of the TH promoter residing at -61
      to -39 bp. Surprisingly, this domain does not contain GATA-3 binding sites but
      possesses a binding motif, a cAMP response element (CRE), for the transcription
      factor, CREB. In addition, we found that site-directed mutation of this CRE
      almost completely abolished transactivation of the TH promoter by GATA-3.
      Furthermore, protein-protein interaction assays showed that GATA-3 is able to
      physically interact with CREB in vitro as well as in vivo. Based on these
      results, we propose that GATA-3 may regulate TH gene transcription via a novel
      and distinct protein-protein interaction, and directly contributes to NA
      phenotype specification.

PMID- 16893420
TI  - Slow and selective death of spinal motor neurons in vivo by intrathecal infusion
      of kainic acid: implications for AMPA receptor-mediated excitotoxicity in ALS.
AB  - Excitotoxicity mediated by alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic
      acid (AMPA) receptors has been proposed to play a major role in the selective
      death of motor neurons in sporadic amyotrophic lateral sclerosis (ALS), and motor
      neurons are more vulnerable to AMPA receptor-mediated excitotoxicity than are
      other neuronal subclasses. On the basis of the above evidence, we aimed to
      develop a rat model of ALS by the long-term activation of AMPA receptors through
      continuous infusion of kainic acid (KA), an AMPA receptor agonist, into the
      spinal subarachnoid space. These rats displayed a progressive motor-selective
      behavioral deficit with delayed loss of spinal motor neurons, mimicking the
      clinicopathological characteristics of ALS. These changes were significantly
      ameliorated by co-infusion with 6-nitro-7-sulfamobenso(f)quinoxaline-2,3-dione
      (NBQX), but not with d(-)-2-amino-5-phosphonovaleric acid (APV), and were
      exacerbated by co-infusion with cyclothiazide, indicative of an AMPA receptor
      mediated mechanism. Among the four AMPA receptor subunits, expression of GluR3
      mRNA was selectively up-regulated in motor neurons but not in dorsal horn neurons
      of the KA-infused rats. The up-regulation of GluR3 mRNA in this model may cause a
      molecular change that induces the selective vulnerability of motor neurons to KA
      by increasing the proportion of GluR2-lacking (i.e. calcium-permeable) AMPA
      receptors. This rat model may be useful in investigating ALS etiology.

PMID- 16893418
TI  - Temporal effects of paraquat/maneb on microglial activation and dopamine neuronal
      loss in older rats.
AB  - We investigated the effects of combined systemic exposure to the herbicide
      paraquat (PQ) and the fungicide maneb (MB) in 6-month-old rats, an animal model
      of Parkinson's disease resulting from environmental toxin exposure. Following two
      doses of PQ (10 mg/kg) and MB (30 mg/kg), 52% of animals developed fatal lung
      injury. Examination of the remaining animals showed degeneration of dopaminergic
      (DA) neurons in the substantia nigra pars compacta 6 weeks, but not 4 weeks,
      following PQ/MB. In contrast, microglial activation was observed at 4 weeks, but
      had abated by 6 weeks. Compared with our previous findings in younger rats, these
      results suggest increased susceptibility of older animals to lung and brain
      toxicity from PQ/MB exposure. Microglial activation preceded, and therefore
      likely contributed to, DA neurodegeneration. Further, electron microscopy
      revealed an abnormal appearance of the Golgi apparatus at 4 weeks that was
      confirmed using double immunostaining for tyrosine hydroxylase and Golgi. This
      suggests that PQ/MB causes protein processing dysfunction in nigral DA neurons
      that may be either a direct effect of PQ/MB or the result of microglial
      activation.

PMID- 16893421
TI  - Cell and agonist-specific regulation of genes for matrix metalloproteinases and
      their tissue inhibitors by primary glial cells.
AB  - An imbalance in the matrix metalloproteinase (MMP) : tissue inhibitor of MMP
      (TIMP) ratio may be associated with tissue injury. Here, we studied the
      regulation of TIMP and MMP gene expression in primary glial cultures to ascertain
      the factors involved in the regulation of these genes in conditions of
      inflammatory neuropathology. Astrocytes were found to basally express TIMP-1 and
      TIMP-3 mRNA while microglia expressed only TIMP-2 mRNA. TIMP-4 mRNA was not
      detectable in either cell type. Treatment with interferon-alpha (IFN-alpha), IFN
      gamma, interleukin-3 (IL-3), IL-6 or tumor necrosis factor-alpha (TNF-alpha) did
      not alter expression of the TIMP genes. However, in astrocytes, but not in
      microglia, serum, IL-1beta or lipopolysaccharide (LPS) evoked a dose- and time
      dependent increase in TIMP-1 mRNA and a coincident down-regulation of the TIMP-3
      gene. Astrocytes were found to express mRNA constitutively for MMPs -3, -11 and 
      14. In contrast, microglia expressed only MMP-12 mRNA under basal conditions. IL
      1beta enhanced MMP-3 mRNA levels while LPS increased the MMP-3, -9, -12, -13 and 
      14 mRNAs. Our findings reveal that regulatory control of TIMP and MMP gene
      expression by glial cells is agonist- and cell-type specific, and suggest that
      innate immune signals govern the temporal and spatial expression patterns of TIMP
      and MMP genes in neuroinflammatory conditions of the CNS.

PMID- 16893422
TI  - Implication of the proprotein convertase NARC-1/PCSK9 in the development of the
      nervous system.
AB  - Neural apoptosis-regulated convertase-1/proprotein convertase subtilisin-kexin
      like-9 (NARC-1/PCSK9) is a proprotein convertase recently described to play a
      major role in cholesterol homeostasis through enhanced degradation of the low
      density lipoprotein receptor (LDLR) and possibly in neural development. Herein,
      we investigated the potential involvement of this proteinase in the development
      of the CNS using mouse embryonal pluripotent P19 cells and the zebrafish as
      models. Time course quantitative RT-PCR analyses were performed following
      retinoic acid (RA)-induced neuroectodermal differentiation of P19 cells.
      Accordingly, the mRNA levels of NARC-1/PCSK9 peaked at day 2 of differentiation
      and fell off thereafter. In contrast, the expression of the proprotein
      convertases subtilisin kexin isozyme 1/site 1 protease and Furin was unaffected
      by RA, whereas that of PC5/6 and PC2 increased within and/or after the first 4
      days of the differentiation period respectively. This pattern was not affected by
      the cholesterogenic transcription factor sterol regulatory element-binding
      protein-2, which normally up-regulates NARC-1/PCSK9 mRNA levels in liver.
      Furthermore, in P19 cells, RA treatment did not affect the protein level of the
      endogenous LDLR. This agrees with the unique expression pattern of NARC-1/PCSK9
      in the rodent CNS, including the cerebellum, where the LDLR is not significantly
      expressed. Whole-mount in situ hybridization revealed that the pattern of
      expression of zebrafish NARC-1/PCSK9 is similar to that of mouse both in the CNS
      and periphery. Specific knockdown of zebrafish NARC-1/PCSK9 mRNA resulted in a
      general disorganization of cerebellar neurons and loss of hindbrain-midbrain
      boundaries, leading to embryonic death at approximately 96 h after fertilization.
      These data support a novel role for NARC-1/PCSK9 in CNS development, distinct
      from that in cholesterogenic organs such as liver.

PMID- 16893423
TI  - Identification of potential target genes for RFX4_v3, a transcription factor
      critical for brain development.
AB  - Regulatory factor X4 variant transcript 3 (Rfx4_v3) gene disruption in mice
      demonstrated that interruption of a single allele (heterozygous, +/-) prevented
      formation of the subcommissural organ, resulting in congenital hydrocephalus,
      while interruption of two alleles (homozygous, -/-) caused fatal failure of
      dorsal midline brain structure formation. To identify potential target genes for
      RFX4_v3, we used microarray analysis to identify differentially expressed genes
      in Rfx4_v3-deficient mouse brains at embryonic day 10.5, before gross structural
      changes were apparent. Of 109 differentially expressed transcripts, 24 were
      chosen for validation and 22 were confirmed by real-time PCR. Many validated
      genes encoded critical proteins involved in brain morphogenesis, such as the
      signaling components in the Wnt, bone morphogenetic protein (BMP) and retinoic
      acid (RA) pathways. Cx3cl1, a CX3C-type chemokine gene that is highly expressed
      in brain, was down-regulated in the Rfx4_v3-null mice. Both human and mouse
      Cx3cl1 proximal promoters contained highly conserved X-boxes, known cis-acting
      elements for RFX protein binding. Using the Cx3cl1 promoter as an example of a
      target gene, we demonstrated direct binding of RFX4_v3 to the Cx3cl1 promoter,
      and trans-acting activity of RFX4_v3 protein to stimulate gene expression. These
      data suggest that RFX4_v3 may act upstream of critical signaling pathways in the
      process of brain development.

PMID- 16893424
TI  - Cannabinoid receptors in human astroglial tumors.
AB  - In animal models, cannabinoids are reported to inhibit the growth of tumors,
      including gliomas. These effects have been claimed to be mediated via cannabinoid
      receptors 1 and 2 (CB1, CB2). To elucidate a possible relevance for treatment of
      human gliomas, we investigated receptor subtype expression in surgical material
      of solid human astrocytomas, gliomas and cultivated glioma cells by quantitative
      reverse transcriptase polymerase chain reaction, western blot and
      immunohistochemistry and assayed their functionality. In normal brain, cultivated
      glioma cells and solid tumors, CB1 mRNA was expressed to a much greater extent
      than CB2, which in some samples was even undetectable. Expression of both
      receptor subtypes was unrelated to malignancy, varied between patients, and was
      not significantly increased in relation to normal brain tissues. In normal brain,
      CB1 protein was localized on astroglial and other cell types; in gliomas, it was
      found on astroglial/glioma cells. CB2 protein was detected on microglial
      cells/macrophages but rarely on astroglial cells. Functionally, CB1 receptor
      agonists reduced elevated cyclic AMP levels and slightly reduced proliferation of
      glioma cells in vitro, but did not induce apoptosis. We conclude that cannabinoid
      therapy of human gliomas targets not only receptors on tumor, but also on other
      cell types. Therefore, complex and potential side-effects should be considered
      carefully.

PMID- 16893425
TI  - Down-regulation of vesicular glutamate transporters precedes cell loss and
      pathology in Alzheimer's disease.
AB  - Alzheimer's disease (AD) is characterized pathologically by plaques, tangles, and
      cell and synapse loss. As glutamate is the principle excitatory neurotransmitter
      of the CNS, the glutamatergic system may play an important role in AD. An
      essential step in glutamate neurotransmission is the concentration of glutamate
      into synaptic vesicles before release from the presynaptic terminal. Recently a
      group of proteins responsible for uptake has been identified - the vesicular
      glutamate transporters (VGLUTs). The generation of antibodies has facilitated the
      study of glutamatergic neurones. Here, we used antibodies to the VGLUTs together
      with immunohistochemistry and western blotting to investigate the status of
      glutamatergic neurones in temporal, parietal and occipital cortices of patients
      with AD; these regions were chosen to represent severely, moderately and mildly
      affected regions at the end stage of the disease. There was no change in
      expression of the synaptic markers in relation to total protein in the temporal
      cortex, but a significant reduction in synaptophysin and VGLUT1 was found in both
      the parietal and occipital cortices. These changes were found to relate to the
      number of tangles in the temporal cortex. There were no correlations with either
      mental test score or behaviour syndromes, with the exception of depression.

PMID- 16893426
TI  - Induction of microglial apoptosis by corticotropin-releasing hormone.
AB  - Neuropeptides are short-chain peptides found in brain tissue, some of which
      function as neurotransmitters and others as hormones. Neuropeptides may directly
      or indirectly modulate glial functions in the CNS. In the present study, effects
      of various neuropeptides on the viability and inflammatory activation of cultured
      microglia were investigated. Vasoactive intestinal peptide, substance P,
      cholecystokinin and neuropeptide Y did not affect microglial cell viability,
      whereas corticotropin-releasing hormone (CRH) induced a classical apoptosis of
      mouse microglia in culture as shown by nuclear condensation and fragmentation,
      terminal deoxynucleotidyl transferase dUTP nick-end labeling, and cleavage of
      caspase 3 and poly(ADP-ribose) polymerase protein. CRH, however, did not
      influence nitric oxide production or expression of inflammatory genes including
      those encoding cytokines and chemokines, indicating that CRH did not affect the
      inflammatory activation of microglia. The CRH-induced microglial apoptosis
      appeared to involve a mitochondrial pathway and reactive oxygen species, based on
      the mitochondrial membrane potential change, caspase 9 activation and sensitivity
      to antioxidants. Taken together, our results indicate that the stress
      neuropeptide CRH may regulate neuroinflammation by inducing the apoptosis of
      microglia, the major cellular source of inflammatory mediators in the CNS.

PMID- 16893429
TI  - Metabolic approach to heart failure - evidence that trimetazidine improves
      symptoms, left ventricular function and possibly prognosis.

PMID- 16893427
TI  - Peptide neuroprotection through specific interaction with brain tubulin.
AB  - This study aimed to identify the neuronal target for the potent neuroprotective
      peptide NAP. When added to pheochromocytoma cells (neuronal model), NAP was found
      in the intracellular milieu and was co-localized with microtubules. NAP induced
      neurite outgrowth and protected primary neurons against microtubule-associated
      ZnCl2 toxicity. Rapid microtubule reorganization into distinct microtubules
      ensued after NAP addition to both pheochromocytoma cells and primary cerebral
      cortical neurons, but not to fibrobalsts. While binding neuronal tubulin and
      protecting pheochromocytoma cells against oxidative stress, NAP did not bind
      tubulin extracted from fibroblasts, nor did it protect those cells against
      oxidative stress. Affinity chromatography identified the brain-specific betaIII
      tubulin as a major NAP binding protein. Paclitaxel (a microtubule aggregating
      agent that interacts with beta-tubulin) reduced NAP tubulin binding. Thus, the
      underlying mechanism for the neuroprotection offered by NAP is targeting neuronal
      microtubules that are essential for neuronal survival and function.

PMID- 16893430
TI  - CATIE for clinicians.

PMID- 16893431
TI  - PDE-5 inhibitors: spoilt for choice.

PMID- 16893432
TI  - Measuring the impact of childhood atopic dermatitis.

PMID- 16893433
TI  - Effect of orlistat in overweight poorly controlled Chinese female type 2 diabetic
      patients: a randomised, double-blind, placebo-controlled study.
AB  - The aim of the study was to assess the adjunctive effects of orlistat on weight
      loss and the influence of weight reduction on glycaemic control in overweight
      Chinese female type 2 diabetic patients. A randomised, placebo-controlled, double
      blind, 12-week study was conducted. Chinese female type 2 diabetic patients,
      overweight (body mass index > 25 kg/m(2)), poorly controlled glucose levels
      [glycosylated haemoglobin (HbA1c) > 8%], were randomly assigned to two groups. In
      addition to their oral hypoglycaemic agents (maximal doses of sulphonylureas and
      metformin), one group (n = 30) received a placebo and the other (n = 30) received
      orlistat 120 mg t.i.d. for 12 weeks. Comparing the changes that occurred after 12
      weeks in the orlistat and placebo groups, the former showed significantly greater
      reduction in bodyweight (2.5 vs. 0.4 kg; p < 0.05), fasting plasma insulin level
      (p < 0.01), 2-h postprandial blood glucose after glucose challenge (p < 0.01),
      insulin resistance (p < 0.01), HbA1c (p < 0.05), total cholesterol and
      triglyceride levels (p < 0.05, respectively). No significant differences were
      found between treatment groups in blood pressure and heart rate. The addition of
      orlistat to oral hypoglycaemic agents resulted in a significant weight reduction
      and improvement of metabolic control in overweight Chinese female type 2 diabetic
      patients.

PMID- 16893434
TI  - Efficacy, safety and LDL-C goal attainment of ezetimibe 10 mg-simvastatin 20 mg
      vs. placebo-simvastatin 20 mg in UK-based adults with coronary heart disease and
      hypercholesterolaemia.
AB  - It is increasingly accepted that more intensive lipid-lowering treatment is
      associated with greater cardiovascular risk reductions in patients with coronary
      heart disease (CHD), thus providing a rationale for more aggressive LDL
      cholesterol (LDL-C) targets. Ezetimibe in combination with statin therapy
      provides an additional approach to lipid management by utilising the additive
      action of two different mechanisms of LDL-C reduction. In this multicentre,
      randomised, double-blind, placebo-controlled study, a total of 98 men and 55
      women with CHD and primary hypercholesterolaemia, naive to statin therapy, were
      randomised to receive treatment for 6 weeks with either ezetimibe 10 mg
      simvastatin 20 mg (n = 77) or placebo-simvastatin 20 mg (n = 75). At 6 weeks,
      ezetimibe 10 mg-simvastatin 20 mg provided a mean additional LDL-C reduction of
      14.6% (95% CI 10.1-19.1) compared with simvastatin monotherapy (p < 0.0001).
      Moreover, a higher proportion of patients on ezetimibe/simvastatin achieved the
      National Standard Framework LDL-C standard (<3.0 mmol/l; 93% vs. 75%, p < 0.001)
      or the new Joint British Societies (JBS 2) goal of LDL-C < 2.0 mmol/l (49.3% vs.
      11.1%, p < 0.001). On logistic regression analysis, the odds ratio of achieving
      target LDL-C with ezetimibe 10 mg-simvastatin 20 mg was 5.1 (95% CI 1.8-15.0)
      times higher than with simvastatin monotherapy (p = 0.003). Clinical chemistry
      profiles and proportions of adverse events were similar in both groups at
      baseline and follow-up. In conclusion, ezetimibe 10 mg-simvastatin 20 mg is a
      practical, effective and safe option for the treatment of primary
      hypercholesterolaemia in CHD patients, and brings more patients to new aggressive
      cholesterol targets compared with simvastatin 20 mg monotherapy.

PMID- 16893436
TI  - Schizophrenia, Clinical Antipsychotic Trials of Intervention Effectiveness
      (CATIE) and number needed to treat: how can CATIE inform clinicians?
AB  - The schizophrenia medication study conducted as part of the Clinical
      Antipsychotic Trials of Intervention Effectiveness (CATIE) provided a large
      quantity of data. However, placing these data into a clinically meaningful
      context for the individual practitioner has been challenging. Effectiveness and
      safety outcome data were extracted from the three principal publications that
      documented the results of phases 1 and 2 of the CATIE schizophrenia study. Number
      needed to treat (NNT) and number needed to harm (NNH) were calculated from the
      categorical results, together with their confidence intervals. Olanzapine and
      clozapine demonstrated advantages over comparators in terms of all-cause
      discontinuation, largely driven by efficacy advantages. NNT for olanzapine
      compared with perphenazine, quetiapine, risperidone and ziprasidone ranged from
      5.5 to 10.1 in phase 1. NNT for clozapine compared with risperidone or quetiapine
      was approximately 3 in phase 2. There were marked differences in association with
      weight gain and metabolic effects, with olanzapine demonstrating a NNH ranging
      from 12.4 to 17.7 in terms of discontinuation of treatment in phase 1 because of
      these effects. Results from phase 2 reflect phase 1 in this regard, and
      demonstrated an advantage for ziprasidone in terms of discontinuation because of
      weight gain or metabolic effects, with NNT ranging from 10.6 to 20.8. However,
      these notable differences in association with weight gain and metabolic effects
      did not seem to drive the differences in overall time to all-cause
      discontinuation. NNT and NNH can help place the wide array of CATIE results into
      clinical context, and permits quantification of the differences observed between
      the antipsychotics that were tested.

PMID- 16893435
TI  - A cost-effectiveness analysis of n-3 PUFA (Omacor) treatment in post-MI patients.
AB  - This study evaluates the cost-effectiveness of Omacor treatment as a standard
      prevention measure post-MI in the UK. A cost-effectiveness model was developed
      based on the GISSI-P trial, combining a survival and a Markov model, over a
      lifetime period. The base case results for Omacor, at 4 years and over a
      lifetime, respectively, were: cost [corrected] per QALY gained: pound15,189 and
      3,723; [corrected] cost per life years gained (LYG): pound12,011 and pound2,812
      [corrected] The cost per death avoided at 4 years was pound31,786. Deterministic
      and probabilistic sensitivity analyses did not change the base case results
      substantially. The use of Omacor as a standard post-MI prevention treatment seems
      warranted in the UK, both on the basis of its efficacy, which is in addition to
      other prophylactic treatments as evidenced by the results of the GISSI-P trial,
      and on cost-effectiveness grounds - both at 4 years and over a lifetime's time
      horizon, using the current cost-effectiveness thresholds.

PMID- 16893437
TI  - Epidemiology, prescribing patterns and resource use associated with overactive
      bladder in UK primary care.
AB  - This study aimed to estimate the incidence and prevalence of overactive bladder
      (OAB) symptoms in the UK and analyse the use of anticholinergic/antispasmodic
      medications and other healthcare resources within UK general practice. Patients
      with a record of urinary frequency, urgency, nocturia, urge incontinence or
      irritable/unstable bladder between 1987 and 2004 were identified from the General
      Practice Research Database. Demographic characteristics, referrals,
      consultations, investigations and prescriptions for medications licensed for use
      in OAB were identified. Regression analyses were used to identify the factors
      determining switches between medications, referrals and use of healthcare
      resources. The overall prevalence of OAB-related symptoms was 3.87 per 1000
      persons, with an incidence of 2.79 per 1000 person-years. Among 68,910 patients
      with OAB symptoms, 19,444 (28.2%) received anticholinergic medication, of whom
      14,454 (74.3%) received one drug and 4055 (20.9%) received two medications
      sequentially. Overall, 59.1% of patients were referred to relevant secondary care
      specialities, 2.8% underwent urinary tests/investigations in primary care and
      0.2% were seen by a continence nurse. Resource use was higher among patients who
      tried several different medications. In conclusion, this study suggests that OAB
      may be under-diagnosed in the UK and that current guidelines recommending use of
      anticholinergic medication, continence nurse consultations and urinary
      tests/investigations are inadequately followed.

PMID- 16893438
TI  - Solifenacin significantly improves all symptoms of overactive bladder syndrome.
AB  - Overactive bladder syndrome (OAB) is a chronic condition characterised by
      urgency, with or without associated urge incontinence. Solifenacin succinate is a
      once daily, bladder selective antimuscarinic available in two doses (5 and 10
      mg). The recommended dose is 5 mg once daily and can be increased to 10 mg once
      daily if 5 mg is well tolerated. This article presents pooled efficacy and safety
      data from four large, placebo-controlled, multinational phase III trials of
      solifenacin succinate with a total enrolment of over 2800 patients. Data from
      these trials show that solifenacin 5 and 10 mg once daily is significantly more
      effective than placebo at reducing urgency, incontinence, micturition frequency
      and nocturia and at increasing volume voided per micturition. Adverse events were
      mainly mild-to-moderate in all treatment groups. The results of these phase III
      trials support the use of solifenacin in the treatment of OAB.

PMID- 16893439
TI  - Management of advanced HIV disease in patients with tuberculosis or hepatitis co
      infection.
AB  - Advanced human immunodeficiency virus (HIV) disease can be defined as a cluster
      of differentiation 4 (CD4) count <50 cells/mm(3) or the presence of an acquired
      immunodeficiency syndrome (AIDS)-defining illness. In the UK and Ireland, the
      number of patients who present with advanced HIV disease is increasing, with
      301/977 (31%) of patients presenting late (<200 CD4 cells/mm(3)). Many patients
      who present with advanced HIV disease will have comorbid conditions, such as
      hepatitis B or C or tuberculosis (TB), which complicates the choice of therapy.
      This article reviews the evidence and some clinical scenarios for specific
      patient groups who may present with advanced HIV disease: those with comorbid TB,
      hepatitis B or hepatitis C. The aim is to offer practical advice on therapeutic
      options for treatment-naive patients who present with advanced HIV disease on the
      basis of available clinical evidence.

PMID- 16893440
TI  - Quality of life and childhood atopic dermatitis: the misery of living with
      childhood eczema.
AB  - The misery of living with atopic eczema (syn. dermatitis, AD) cannot be
      overstated for it may have a profoundly negative effect on the health-related
      quality of life (HRQoL) of children and their family unit in many cases. As it is
      one of the commonest chronic relapsing childhood dermatosis (UK lifetime
      prevalence 16-20% by 20 years), with increasing worldwide prevalence, this has
      major social and financial implications for individuals, healthcare providers and
      society as a whole. This review explores the impact of AD on the lives of
      children and their family units and the use of some of the recently developed
      HRQoL measures, which have enabled investigation and categorisation of the
      physical, psychological and psycho-social effects of childhood eczema across all
      aspects of life. These effects include symptoms of itching and soreness, which
      cause sleeplessness in over 60%. Sleep deprivation leads to tiredness, mood
      changes and impaired psychosocial functioning of the child and family,
      particularly at school and work. Embarrassment, comments, teasing and bullying
      frequently cause social isolation and may lead to depression or school avoidance.
      The child's lifestyle is often limited, particularly in respect to clothing,
      holidays, staying with friends, owning pets, swimming or the ability to play or
      do sports. Restriction of normal family life, difficulties with complicated
      treatment regimes and increased work in caring for a child with eczema lead to
      parental exhaustion and feelings of hopelessness, guilt, anger and depression.
      The hidden costs involved in eczema management can be significant and have
      particular impact on lower income families. The impairment of quality of life
      caused by childhood eczema has been shown to be greater than or equal to other
      common childhood diseases such as asthma and diabetes, emphasising the importance
      of eczema as a major chronic childhood disease. HRQoL measures are proving to be
      valuable tools for use in the clinical setting, as outcome measures for
      pharmaceutical studies, for health economics and audit purposes. It is therefore
      recommended that in future, they should be used in conjunction with objective
      measures of severity, as part of the assessment process of a child with atopic
      eczema. Lack of information on eczema and treatments heightens parental anxiety.
      Education of all individuals involved in the care of children with eczema is
      fundamental in the management of AD and it is essential to provide simple clear,
      unambiguous information on treatment and disease management in order to reduce
      the negative impact on HRQoL.

PMID- 16893441
TI  - Platelet inhibition beyond conventional antiplatelet agents: expanding role of
      angiotensin receptor blockers, statins and selective serotonin reuptake
      inhibitors.
AB  - Aspirin, dipyridamole, cilostazol, thienopyridines and glycoprotein IIb/IIIa
      inhibitors represent the classical examples of the established antiplatelet
      agents commonly used for the secondary prevention in patients after vascular
      events. Obviously, the era of expanding antiplatelet regimens and indications may
      require new agents as the substitutes, or additions to the available strategies.
      However, recent results of the majority of antiplatelet trials strongly suggest
      boarder line advantages in clinical outcomes, and higher associated bleeding
      risks with the novel antiplatelet agents or/and regimens. Moreover, unexpected
      failures, such as lack of efficacy of clopidogrel and aspirin combination for
      ischaemic stroke prevention (MATCH), or use of the same antiplatelet regimen for
      the primary vascular prevention (CHARISMA) raise legitimate concerns that the
      concept 'the more the better' may not be valid. Broad use of statins, angiotensin
      receptor blockers and selective serotonin reuptake inhibitors may be in part
      responsible for the lack of impressive results with the antiplatelet therapy
      because each of these drug classes per se inhibits platelets. In this review, we
      discuss the available evidence and potential clinical significance of these
      findings.

PMID- 16893442
TI  - Baclofen: a new drug for the treatment of alcohol dependence.
AB  - Recent preclinical and clinical studies have suggested that baclofen, the
      prototypic gamma-aminobutyric acid B (GABA(B)) receptor agonist, is a promising
      pharmacological compound for use in the treatment of alcohol dependence. In
      particular, baclofen has been found to suppress symptoms of alcohol withdrawal
      syndrome with an efficacy comparable with that of the 'gold standard' diazepam.
      Moreover, baclofen has proven effective in the prevention of relapse due to its
      ability to reduce alcohol intake and craving in alcoholic patients. Baclofen
      proved to be manageable, producing no significant side effects and displaying no
      addictive properties. The efficacy of the drug in the management of both alcohol
      withdrawal syndrome and relapse prevention should entail a vastly simplified
      pharmacotherapy of alcohol dependence.

PMID- 16893444
TI  - Response to: Ethics, data and the pharmaceutical physician.

PMID- 16893445
TI  - Response to: Angiotensin receptor blockers in hypertension: the emerging role in
      diabetes mellitus.

PMID- 16893446
TI  - Risk factors for vitamin D inadequacy among women with osteoporosis: an
      international epidemiological study.
AB  - A serum 25-hydroxyvitamin D [25(OH)D] level of 75 nmol/l (30 ng/ml) has been
      proposed as the minimum for adequate vitamin D nutrition as lower levels are
      associated with increases in serum parathyroid hormone in otherwise healthy
      adults. Amongst 2589 community-dwelling, postmenopausal women with osteoporosis
      from 18 countries, recruited to determine risk factors for vitamin D inadequacy,
      64% had vitamin D inadequacy. General health, education, ethnicity, sun exposure,
      skin reactivity, diet, recent travel to sunny climates, vitamin D
      supplementation, body mass index (BMI), season and latitude were assessed using
      logistic regression models. Asian ethnicity, BMI >or=30 kg/m(2), living in non
      equatorial countries, inadequate vitamin D supplementation, poor/fair health, no
      education about vitamin D, skin reactivity and no recent travel to sunny areas
      were significant predictors. Several modifiable risk factors are associated with
      vitamin D inadequacy worldwide, suggesting potentially simple ways to increase
      vitamin D and improve bone health in postmenopausal women.

PMID- 16893447
TI  - Exposure of hairdressing apprentices to airborne hazardous substances.
AB  - BACKGROUND: Few studies have investigated exposure of hairdressing apprentices to
      airborne irritants. This study describes exposure levels of apprentices to
      chemical products used in hairdressing salons in relation with their activity.
      METHODS: Following a two stages study design, a group of 300 students completed a
      questionnaire on their work activities and environment. Among these, a group of
      28 subjects volunteered to undergo personal exposure and workplace concentrations
      measurements over a work shift, during a cold and a hot season, with the
      agreement of the salon owners. Three chemical substances were studied (ammonia,
      hydrogen peroxide and persulfates) because they are respiratory tract irritants
      and because their concentrations could be quantified within a 5 to 8 hour shift
      period. RESULTS: Personal exposure values for H2O2 and NH3 (averages [standard
      deviations] are 0.05 [0.04] and 0.90 [0.76] mg.m(-3), respectively) were greater
      than workplace ambient air concentrations (corresponding values of 0.04 [0.03]
      and 0.68 [0.42] mg.m(-3)) for H2O2 and NH3, with no significant seasonal
      variation. By contrast, workplace concentrations of persulfates (0.019 [0.018]
      mg.m(-3)) were greater than personal exposure (0.016 [0.021] mg.m(-3), a finding
      that is consistent with the fact that bleaching is more often undertaken by
      senior hairdressers. However, all exposure values were lower than the current TLV
      TWA values. This study also shows that over half of technical spaces where
      chemical substances used for dying, permanenting or bleaching are manipulated,
      have no ventilation system, and not even a door or a window opening outside.
      CONCLUSION: The study hairdressing salons, on average, were small, the most
      probable reason why occupational hygiene measures such as appropriate ventilation
      were too seldom implemented. As a consequence, young apprentices and senior
      hairdressers experience substantial exposure to known airways irritants.

PMID- 16893448
TI  - Modest phenotypic improvements in ASA-deficient mice with only one UDP
      galactose:ceramide-galactosyltransferase gene.
AB  - BACKGROUND: Arylsulfatase A (ASA)-deficient mice are a model for the lysosomal
      storage disorder metachromatic leukodystrophy. This lipidosis is characterised by
      the lysosomal accumulation of the sphingolipid sulfatide. Storage of this lipid
      is associated with progressive demyelination. We have mated ASA-deficient mice
      with mice heterozygous for a non-functional allele of UDP-galactose:ceramide
      galactosyltransferase (CGT). This deficiency is known to lead to a decreased
      synthesis of galactosylceramide and sulfatide, which should reduce sulfatide
      storage and improve pathology in ASA-deficient mice. RESULTS: ASA-/- CGT+/- mice,
      however, showed no detectable decrease in sulfatide storage. Neuronal
      degeneration of cells in the spiral ganglion of the inner ear, however, was
      decreased. Behavioural tests showed small but clear improvements of the phenotype
      in ASA-/- CGT+/- mice. CONCLUSION: Thus the reduction of galactosylceramide and
      sulfatide biosynthesis by genetic means overall causes modest improvements of
      pathology.

PMID- 16893450
TI  - Effects of dopexamine on the intestinal microvascular blood flow and leukocyte 
      activation in a sepsis model in rats.
AB  - INTRODUCTION: The administration of dopexamine may constitute a therapeutical
      option to improve hepatosplanchnic perfusion in sepsis. In order to verify this
      hypothesis, we administered dopexamine in an experimental sepsis model in rats.
      METHODS: This prospective, randomized, controlled laboratory study was conducted
      in 42 Wistar rats. The animals were divided into 3 groups. Group 1 (CON group)
      served as control group. The Animals of groups 2 (LPS Group) and 3 received an
      endotoxin infusion (20 mg/kgfor 15 min). In addition, in group 3 (DPX group)
      dopexamine was administered 0.5 microg/kg/minover 4 hours. One half of the
      animals of each group underwent studies of intestinal microvascular blood flow
      (IMBF) using laser Doppler fluxmetry. In the other half an intravital microscopic
      evaluation of the leukocyte endothelium cell interaction in the intestinal
      microcirculation was performed. Functional capillary denstity (FCD) in the
      intestinal mucosaand the circular as well as the longitudinal muscle layer was
      estimated. RESULTS: One hour after endotoxin challenge IMBF decreased
      significantly in the untreated LPS group to 51% compared to baseline (p<0.05). In
      DPX treated endotoxin animals we found significantly higher values at the level
      of CON group. The after endotoxin challenge impaired FCD was improved by
      dopexamine in the longitudinal (DPX + 33% vs. LPS; p <0.05) and in the circular
      muscle layer (DPX + 48% vs. LPS; p < 0.05) as a result of dopexamine
      administration. The administration of dopexamine reduced the count of firmly
      adherent leukocytes when compared to the untreated LPS group (-31%, p<0.05). TNF
      alpha plasma levels were reduced by dopexamine infusion (LPS group 3637 +/- 553
      pg/mL; DPXgroup 1933 +/- 201 pg/mL) one hour after endotoxin challenge.
      CONCLUSIONS: The administration of dopexamine improved IMBF and FCD as parameters
      of intestinal microcirculation and reduced leukocyte activation as a parameter of
      inflammation in experimental sepsis.

PMID- 16893449
TI  - Effect of SWI/SNF chromatin remodeling complex on HIV-1 Tat activated
      transcription.
AB  - BACKGROUND: Human immunodeficiency virus type 1 (HIV-1) is the etiologic agent of
      acquired immunodeficiency virus (AIDS). Following entry into the host cell, the
      viral RNA is reverse transcribed into DNA and subsequently integrated into the
      host genome as a chromatin template. The integrated proviral DNA, along with the
      specific chromatinized environment in which integration takes place allows for
      the coordinated regulation of viral transcription and replication. While the
      specific roles of and interplay between viral and host proteins have not been
      fully elucidated, numerous reports indicate that HIV-1 retains the ability for
      self-regulation via the pleiotropic effects of its viral proteins. Though viral
      transcription is fully dependent upon host cellular factors and the state of host
      activation, recent findings indicate a complex interplay between viral proteins
      and host transcription regulatory machineries including histone deacetylases
      (HDACs), histone acetyltransferases (HATs), cyclin dependent kinases (CDKs), and
      histone methyltransferases (HMTs). RESULTS: Here, we describe the effect of Tat
      activated transcription at the G1/S border of the cell cycle and analyze the
      interaction of modified Tat with the chromatin remodeling complex, SWI/SNF. HIV-1
      LTR DNA reconstituted into nucleosomes can be activated in vitro using various
      Tat expressing extracts. Optimally activated transcription was observed at the
      G1/S border of the cell cycle both in vitro and in vivo, where chromatin
      remodeling complex, SWI/SNF, was present on the immobilized LTR DNA. Using a
      number of in vitro binding as well as in vivo chromatin immunoprecipitation
      (ChIP) assays, we detected the presence of both BRG1 and acetylated Tat in the
      same complex. Finally, we demonstrate that activated transcription resulted in
      partial or complete removal of the nucleosome from the start site of the LTR as
      evidenced by a restriction enzyme accessibility assay. CONCLUSION: We propose a
      model where unmodified Tat is involved in binding to the CBP/p300 and cdk9/cyclin
      T1 complexes facilitating transcription initiation. Acetylated Tat dissociates
      from the TAR RNA structure and recruits bromodomain-binding chromatin modifying
      complexes such as p/CAF and SWI/SNF to possibly facilitate transcription
      elongation.

PMID- 16893452
TI  - Relationship between objective measures of physical activity and weather: a
      longitudinal study.
AB  - BACKGROUND: The weather may be a barrier to physical activity but objective
      assessment of this hypothesis is lacking. Therefore we evaluated the effect of
      temperature, rain or snow, and wind speed on the daily physical activity of
      adults. METHODS: This report contains data from 25 males (BMI (mean +/- SD): 28.7
      +/- 3.83 kg/m2) and 177 females (BMI: 29.2 +/- 5.92 kg/m2) enrolled in an
      intervention to increase physical activity. Steps/day of the participants was
      measured by pedometer. Weather data were obtained from Environment Canada. A
      total of 8,125 observations were included in a mixed linear model analysis.
      RESULTS: Significant weather related variables (at the 5% level) impacting
      steps/day included: seasonal effects related to the interaction between weekday
      and month; mean temperature, total rainfall, interactions between gender, BMI and
      total snow, interactions between maximum wind speed and BMI, and the amount of
      snow on the ground. The estimated magnitudes for the various effects were modest,
      ranging from approximately 1% to approximately 20%. Thus for an average
      individual taking approximately 10,000 steps/day, weather-dependent changes in
      physical activity could reach 2,000 steps/day. CONCLUSION: We conclude that
      weather had modest effects on physical activity of participants in an
      intervention to increase their activity. It should be stressed that these effects
      may be different for less or more motivated people. With this in mind, we suggest
      that the effect of weather on physical activity in the general population needs
      to be objectively assessed to better understand the barrier it poses, especially
      as it relates to outdoor recreation or work activities.

PMID- 16893451
TI  - Genetic affinities among the lower castes and tribal groups of India: inference
      from Y chromosome and mitochondrial DNA.
AB  - BACKGROUND: India is a country with enormous social and cultural diversity due to
      its positioning on the crossroads of many historic and pre-historic human
      migrations. The hierarchical caste system in the Hindu society dominates the
      social structure of the Indian populations. The origin of the caste system in
      India is a matter of debate with many linguists and anthropologists suggesting
      that it began with the arrival of Indo-European speakers from Central Asia about
      3500 years ago. Previous genetic studies based on Indian populations failed to
      achieve a consensus in this regard. We analysed the Y-chromosome and
      mitochondrial DNA of three tribal populations of southern India, compared the
      results with available data from the Indian subcontinent and tried to reconstruct
      the evolutionary history of Indian caste and tribal populations. RESULTS: No
      significant difference was observed in the mitochondrial DNA between Indian
      tribal and caste populations, except for the presence of a higher frequency of
      west Eurasian-specific haplogroups in the higher castes, mostly in the north
      western part of India. On the other hand, the study of the Indian Y lineages
      revealed distinct distribution patterns among caste and tribal populations. The
      paternal lineages of Indian lower castes showed significantly closer affinity to
      the tribal populations than to the upper castes. The frequencies of deep-rooted Y
      haplogroups such as M89, M52, and M95 were higher in the lower castes and tribes,
      compared to the upper castes. CONCLUSION: The present study suggests that the
      vast majority (> 98%) of the Indian maternal gene pool, consisting of Indio
      European and Dravidian speakers, is genetically more or less uniform. Invasions
      after the late Pleistocene settlement might have been mostly male-mediated.
      However, Y-SNP data provides compelling genetic evidence for a tribal origin of
      the lower caste populations in the subcontinent. Lower caste groups might have
      originated with the hierarchical divisions that arose within the tribal groups
      with the spread of Neolithic agriculturalists, much earlier than the arrival of
      Aryan speakers. The Indo-Europeans established themselves as upper castes among
      this already developed caste-like class structure within the tribes.

PMID- 16893453
TI  - Indications that "codon boundaries" are physico-chemically defined and that
      protein-folding information is contained in the redundant exon bases.
AB  - BACKGROUND: All the information necessary for protein folding is supposed to be
      present in the amino acid sequence. It is still not possible to provide specific
      ab initio structure predictions by bioinformatical methods. It is suspected that
      additional folding information is present in protein coding nucleic acid
      sequences, but this is not represented by the known genetic code. RESULTS:
      Nucleic acid subsequences comprising the 1st and/or 3rd codon residues in mRNAs
      express significantly higher free folding energy (FFE) than the subsequence
      containing only the 2nd residues (p < 0.0001, n = 81). This periodic FFE
      difference is not present in introns. It is therefore a specific physico-chemical
      characteristic of coding sequences and might contribute to unambiguous definition
      of codon boundaries during translation. The FFEs of the 1st and 3rd residues are
      additive, which suggests that these residues contain a significant number of
      complementary bases and that may contribute to selection for local RNA secondary
      structures in coding regions. This periodic, codon-related structure-formation of
      mRNAs indicates a connection between the structures of exons and the
      corresponding (translated) proteins. The folding energy dot plots of RNAs and the
      residue contact maps of the coded proteins are indeed similar. Residue contact
      statistics using 81 different protein structures confirmed that amino acids that
      are coded by partially reverse and complementary codons (Watson-Crick (WC) base
      pairs at the 1st and 3rd codon positions and translated in reverse orientation)
      are preferentially co-located in protein structures. CONCLUSION: Exons are
      distinguished from introns, and codon boundaries are physico-chemically defined,
      by periodically distributed FFE differences between codon positions. There is a
      selection for local RNA secondary structures in coding regions and this nucleic
      acid structure resembles the folding profiles of the coded proteins. The
      preferentially (specifically) interacting amino acids are coded by partially
      complementary codons, which strongly supports the connection between mRNA and the
      corresponding protein structures and indicates that there is protein folding
      information in nucleic acids that is not present in the genetic code. This might
      suggest an additional explanation of codon redundancy.

PMID- 16893454
TI  - Ethnoveterinary medicines used for horses in Trinidad and in British Columbia,
      Canada.
AB  - This paper investigates the commonalities in ethnoveterinary medicine used for
      horses between Trinidad (West Indies) and British Columbia (Canada). These
      research areas are part of a common market in pharmaceuticals and are both
      involved in the North American racing circuit. There has been very little
      research conducted on medicinal plants used for horses although their use is
      widespread. The data on ethnoveterinary medicines used for horses was obtained
      through key informant interviews with horse owners, trainers, breeders, jockeys,
      grooms and animal care specialists in two research areas: Trinidad and British
      Columbia (BC). A participatory validation workshop was held in BC. An extensive
      literature review and botanical identification of the plants was also done. In
      all, 20 plants were found to be used in treating racehorses in Trinidad and 97 in
      BC. Of these the most-evidently effective plants 19 of the plants used in
      Trinidad and 66 of those used in BC are described and evaluated in this paper.
      Aloe vera, Curcuma longa and Ricinus communis are used in both research areas.
      More research is needed in Trinidad to identify plants that respondents claimed
      were used in the past. Far more studies have been conducted on the temperate and
      Chinese medicinal plants used in BC and therefore these ethnoveterinary remedies
      reflect stronger evidence of efficacy.

PMID- 16893455
TI  - Activation of WNT and BMP signaling in adult human articular cartilage following
      mechanical injury.
AB  - Acute full thickness joint surface defects can undergo repair, which involves
      tissue patterning and endochondral bone formation. Molecular signals regulating
      this process may contribute to the repair outcome, chronic evolution and,
      eventually, the onset of osteoarthritis. We tested the hypothesis that mechanical
      injury modulates morphogenetic pathways in adult human articular cartilage
      explants. Adjacent articular cartilage explants were obtained from preserved
      areas of the femoral condyles of patients undergoing arthroplasty for
      osteoarthritis, or from a normal joint of a patient undergoing lower limb
      amputation. Paired explants were individually maintained in explant culture. From
      each pair, one explant was mechanically injured and the other left uninjured as a
      control. Cultures were terminated at different time points for histochemistry,
      immunohistochemistry and gene expression analysis by reverse transcription real
      time PCR. Bone morphogenetic protein 2 (BMP-2) mRNA was upregulated in the
      injured explants. We detected phosphorylation of SMAD-1 and SMAD-5, consistent
      with activation of the bone morphogenetic protein (BMP) pathway. FRZB-1 mRNA was
      downregulated in the injured explants, suggesting de-repression of WNT signaling.
      Accordingly, expression of the canonical WNT target genes Axin-2 and c-JUN was
      upregulated in the injured explants. Activation of the canonical WNT signaling
      pathway by LiCl treatment induced upregulation of COL2A1 and Aggrecan mRNA,
      suggesting an anabolic effect. Phosphorylation of SMAD-1/-5 and downregulation of
      FRZB were confirmed in vivo in a mouse model of joint surface injury. Taken
      together, these data show modulation of the BMP and WNT pathways following
      mechanical injury in vitro and in vivo, which may play a role in the reparative
      response of the joint surface. These pathways may, therefore, represent potential
      targets in protocols of biological joint surface defect repair.

PMID- 16893456
TI  - TBLR1 regulates the expression of nuclear hormone receptor co-repressors.
AB  - BACKGROUND: Transcription is regulated by a complex interaction of activators and
      repressors. The effectors of repression are large multimeric complexes which
      contain both the repressor proteins that bind to transcription factors and a
      number of co-repressors that actually mediate transcriptional silencing either by
      inhibiting the basal transcription machinery or by recruiting chromatin-modifying
      enzymes. RESULTS: TBLR1 [GenBank: NM024665] is a co-repressor of nuclear hormone
      transcription factors. A single highly conserved gene encodes a small family of
      protein molecules. Different isoforms are produced by differential exon
      utilization. Although the ORF of the predominant form contains only 1545 bp, the
      human gene occupies approximately 200 kb of genomic DNA on chromosome 3q and
      contains 16 exons. The genomic sequence overlaps with the putative DC42 [GenBank:
      NM030921] locus. The murine homologue is structurally similar and is also located
      on Chromosome 3. TBLR1 is closely related (79% homology at the mRNA level) to
      TBL1X and TBL1Y, which are located on Chromosomes X and Y. The expression of
      TBLR1 overlaps but is distinct from that of TBL1. An alternatively spliced form
      of TBLR1 has been demonstrated in human material and it too has an unique pattern
      of expression. TBLR1 and the homologous genes interact with proteins that
      regulate the nuclear hormone receptor family of transcription factors. In resting
      cells TBLR1 is primarily cytoplasmic but after perturbation the protein
      translocates to the nucleus. TBLR1 co-precipitates with SMRT, a co-repressor of
      nuclear hormone receptors, and co-precipitates in complexes immunoprecipitated by
      antiserum to HDAC3. Cells engineered to over express either TBLR1 or N- and C
      terminal deletion variants, have elevated levels of endogenous N-CoR. Co
      transfection of TBLR1 and SMRT results in increased expression of SMRT. This co
      repressor undergoes ubiquitin-mediated degradation and we suggest that the
      stabilization of the co-repressors by TBLR1 occurs because of a novel mechanism
      that protects them from degradation. Transient over expression of TBLR1 produces
      growth arrest. CONCLUSION: TBLR1 is a multifunctional co-repressor of
      transcription. The structure of this family of molecules is highly conserved and
      closely related co-repressors have been found in all eukaryotic organisms.
      Regulation of co-repressor expression and the consequent alterations in
      transcriptional silencing play an important role in the regulation of
      differentiation.

PMID- 16893457
TI  - Exposure of neonates to respiratory syncytial virus is critical in determining
      subsequent airway response in adults.
AB  - BACKGROUND: Respiratory syncytial virus (RSV) is the most common cause of acute
      bronchiolitis in infants and the elderly. Furthermore, epidemiological data
      suggest that RSV infection during infancy is a potent trigger of subsequent
      wheeze and asthma development. However, the mechanism by which RSV contributes to
      asthma is complex and remains largely unknown. A recent study indicates that the
      age of initial RSV infection is a key factor in determining airway response to
      RSV rechallenge. We hypothesized that severe RSV infection during neonatal
      development significantly alters lung structure and the pulmonary immune micro
      environment; and thus, neonatal RSV infection is crucial in the development of or
      predisposition to allergic inflammatory diseases such as asthma. METHODS: To
      investigate this hypothesis the present study was conducted in a neonatal mouse
      model of RSV-induced pulmonary inflammation and airway dysfunction. Seven-day-old
      mice were infected with RSV (2 x 10(5) TCID50/g body weight) and allowed to
      mature to adulthood. To determine if neonatal RSV infection predisposed adult
      animals to enhanced pathophysiological responses to allergens, these mice were
      then sensitized and challenged with ovalbumin. Various endpoints including lung
      function, histopathology, cytokine production, and cellularity in bronchoalveolar
      lavage were examined. RESULTS: RSV infection in neonates alone led to
      inflammatory airway disease characterized by airway hyperreactivity,
      peribronchial and perivascular inflammation, and subepithelial fibrosis in
      adults. If early RSV infection was followed by allergen exposure, this pulmonary
      phenotype was exacerbated. The initial response to neonatal RSV infection
      resulted in increased TNF-alpha levels in bronchoalveolar lavage. Interestingly,
      increased levels of IL-13 and mucus hyperproduction were observed almost three
      months after the initial infection with RSV. CONCLUSION: Neonatal RSV exposure
      results in long term pulmonary inflammation and exacerbates allergic airways
      disease. The early increase in TNF-alpha in the bronchoalveolar lavage implicates
      this inflammatory cytokine in orchestrating these events. Finally, the data
      presented emphasize IL-13 and TNF-alpha as potential therapeutic targets for
      treating RSV induced-asthma.

PMID- 16893459
TI  - The role of urine pregnancy testing in facilitating access to antenatal care and
      abortion services in South Africa: a cross-sectional study.
AB  - BACKGROUND: Effective confirmation of pregnancy is a basic component of
      reproductive health services. It is a prerequisite for accessing antenatal care
      (AnC) if the pregnancy is wanted and abortion services if the pregnancy is
      unwanted. This study examined the role of urine pregnancy testing in the timing
      of presentation for pregnancy-care. METHOD: A cross-sectional study was conducted
      among 158 women presenting for antenatal care and 164 women presenting for
      abortion at public sector clinics in Cape Town, South Africa. RESULTS: The median
      gestational age at first presentation was 23 weeks for AnC clients and 13 weeks
      for abortion clients. Obtaining a urine pregnancy test of one's own accord was
      associated with a decrease in the gestational age at presentation of 3.6 and 1.4
      weeks for antenatal and abortion clients, respectively, independently of all
      other factors. CONCLUSION: Given the proven clinical benefit and public health
      impact of early presentation for antenatal and abortion services, strategies to
      decrease gestational age at presentation for pregnancy care should be given
      priority. 'Fast-track' urine pregnancy testing services should be established in
      public sector clinics in South Africa.

PMID- 16893458
TI  - Long-term impact of four different strategies for delivering an on-line
      curriculum about herbs and other dietary supplements.
AB  - BACKGROUND: Previous research has shown that internet education can lead to short
      term improvements in clinicians' knowledge, confidence and communication
      practices. We wished to better understand the duration of these improvements and
      whether different curriculum delivery strategies differed in affecting these
      improvements. METHODS: As previously described, we conducted a randomized control
      trial comparing four different strategies for delivering an e-curriculum about
      herbs and other dietary supplements (HDS) to clinicians. The four strategies were
      delivering the curriculum by: a) email over 10 weeks; b) email within one week;
      c) web-site over 10 weeks; d) web-site within one week. Participants were
      surveyed at baseline, immediately after the course and 6-10 months after
      completing the course (long-term). Long-term outcomes focused on clinicians'
      knowledge, confidence and communication practices. RESULTS: Of the 780 clinicians
      who completed the course, 385 (49%) completed the long-term survey. Completers
      and non-completers of the long-term survey had similar demographics and
      professional characteristics at baseline. There were statistically significant
      improvements from baseline to long-term follow-up in knowledge, confidence and
      communication practices; these improvements did not differ by curriculum delivery
      strategy. Knowledge scores improved from 67.7 +/- 10.3 at baseline to 78.8 +/-
      12.3 at long-term follow-up (P < 0.001). Confidence scores improved from 53.7 +/-
      17.8 at baseline to 66.9 +/- 12.0 at long term follow-up (P < 0.001);
      communication scores improved from 2.6 +/- 1.9 at baseline to 3.6 +/- 2.1 (P <
      0.001) at long-term follow-up. CONCLUSION: This e- curriculum led to significant
      and sustained improvements in clinicians' expertise about HDS regardless of the
      delivery strategy. Future studies should compare the impact of required vs.
      elective courses and self-reported vs. objective measures of behavior change.

PMID- 16893460
TI  - Global DNA hypermethylation-associated cancer chemotherapy resistance and its
      reversion with the demethylating agent hydralazine.
AB  - BACKGROUND: The development of resistance to cytotoxic chemotherapy continues to
      be a major obstacle for successful anticancer therapy. It has been shown that
      cells exposed to toxic concentrations of commonly used cancer chemotherapy agents
      develop DNA hypermethylation. Hence, demethylating agents could play a role in
      overcoming drug resistance. METHODS: MCF-7 cells were rendered adriamycin
      resistant by weekly treatment with adriamycin. Wild-type and the resulting MCF
      7/Adr cells were analyzed for global DNA methylation. DNA methyltransferase
      activity and DNA methyltransferase (dnmt) gene expression were also determined.
      MCF-7/Adr cells were then subjected to antisense targeting of dnmt1, -3a, and -b
      genes and to treatment with the DNA methylation inhibitor hydralazine to
      investigate whether DNA demethylation restores sensitivity to adriamycin.
      RESULTS: MCF-7/Adr cells exhibited the multi-drug resistant phenotype as
      demonstrated by adriamycin resistance, mdr1 gene over-expression, decreased
      intracellular accumulation of adriamycin, and cross-resistance to paclitaxel. The
      mdr phenotype was accompanied by global DNA hypermethylation, over-expression of
      dnmt genes, and increased DNA methyltransferase activity as compared with wild
      type MCF-7 cells. DNA demethylation through antisense targeting of dnmts or
      hydralazine restored adriamycin sensitivity of MCF-7/Adr cells to a greater
      extent than verapamil, a known inhibitor of mdr protein, suggesting that DNA
      demethylation interferes with the epigenetic reprogramming that participates in
      the drug-resistant phenotype. CONCLUSION: We provide evidence that DNA
      hypermethylation is at least partly responsible for development of the multidrug
      resistant phenotype in the MCF-7/Adr model and that hydralazine, a known DNA
      demethylating agent, can revert the resistant phenotype.

PMID- 16893461
TI  - Phylogenetic analysis of the tenascin gene family: evidence of origin early in
      the chordate lineage.
AB  - BACKGROUND: Tenascins are a family of glycoproteins found primarily in the
      extracellular matrix of embryos where they help to regulate cell proliferation,
      adhesion and migration. In order to learn more about their origins and
      relationships to each other, as well as to clarify the nomenclature used to
      describe them, the tenascin genes of the urochordate Ciona intestinalis, the
      pufferfish Tetraodon nigroviridis and Takifugu rubripes and the frog Xenopus
      tropicalis were identified and their gene organization and predicted protein
      products compared with the previously characterized tenascins of amniotes.
      RESULTS: A single tenascin gene was identified in the genome of C. intestinalis
      that encodes a polypeptide with domain features common to all vertebrate
      tenascins. Both pufferfish genomes encode five tenascin genes: two tenascin-C
      paralogs, a tenascin-R with domain organization identical to mammalian and avian
      tenascin-R, a small tenascin-X with previously undescribed GK repeats, and a
      tenascin-W. Four tenascin genes corresponding to tenascin-C, tenascin-R, tenascin
      X and tenascin-W were also identified in the X. tropicalis genome. Multiple
      sequence alignment reveals that differences in the size of tenascin-W from
      various vertebrate classes can be explained by duplications of specific
      fibronectin type III domains. The duplicated domains are encoded on single exons
      and contain putative integrin-binding motifs. A phylogenetic tree based on the
      predicted amino acid sequences of the fibrinogen-related domains demonstrates
      that tenascin-C and tenascin-R are the most closely related vertebrate tenascins,
      with the most conserved repeat and domain organization. Taking all lines of
      evidence together, the data show that the tenascins referred to as tenascin-Y and
      tenascin-N are actually members of the tenascin-X and tenascin-W gene families,
      respectively. CONCLUSION: The presence of a tenascin gene in urochordates but not
      other invertebrate phyla suggests that tenascins may be specific to chordates.
      Later genomic duplication events led to the appearance of four family members in
      vertebrates: tenascin-C, tenascin-R, tenascin-W and tenascin-X.

PMID- 16893462
TI  - Characterization of the mrgRS locus of the opportunistic pathogen Burkholderia
      pseudomallei: temperature regulates the expression of a two-component signal
      transduction system.
AB  - BACKGROUND: Burkholderia pseudomallei is a saprophyte in tropical environments
      and an opportunistic human pathogen. This versatility requires a sensing
      mechanism that allows the bacterium to respond rapidly to altered environmental
      conditions. We characterized a two-component signal transduction locus from B.
      pseudomallei 204, mrgR and mrgS, encoding products with extensive homology with
      response regulators and histidine protein kinases of Escherichia coli, Bordetella
      pertussis, and Vibrio cholerae. RESULTS: The locus was present and expressed in a
      variety of B. pseudomallei human and environmental isolates but was absent from
      other Burkholderia species, B. cepacia, B. cocovenenans, B. plantarii, B.
      thailandensis, B. vandii, and B. vietnamiensis. A 2128 bp sequence, including the
      full response regulator mrgR, but not the sensor kinase mrgS, was present in the
      B. mallei genome. Restriction fragment length polymorphism downstream from mrgRS
      showed two distinct groups were present among B. pseudomallei isolates. Our
      analysis of the open reading frames in this region of the genome revealed that
      transposase and bacteriophage activity may help explain this variation. MrgR and
      MrgS proteins were expressed in B. pseudomallei 204 cultured at different pH,
      salinity and temperatures and the expression was substantially reduced at 25
      degrees C compared with 37 degrees C or 42 degrees C but was mostly unaffected by
      pH or salinity, although at 25 degrees C and 0.15% NaCl a small increase in MrgR
      expression was observed at pH 5. MrgR was recognized by antibodies in
      convalescent sera pooled from melioidosis patients. CONCLUSION: The results
      suggest that mrgRS regulates an adaptive response to temperature that may be
      essential for pathogenesis, particularly during the initial phases of infection.
      B. pseudomallei and B. mallei are very closely related species that differ in
      their capacity to adapt to changing environmental conditions. Modifications in
      this region of the genome may assist our understanding of the reasons for this
      difference.

PMID- 16893463
TI  - Does a competitive voucher program for adolescents improve the quality of
      reproductive health care? A simulated patient study in Nicaragua.
AB  - BACKGROUND: Little is known about how sexual and reproductive (SRH) health can be
      made accessible and appropriate to adolescents. This study evaluates the impact
      and sustainability of a competitive voucher program on the quality of SRH care
      for poor and underserved female adolescents and the usefulness of the simulated
      patient (SP) method for such evaluation. METHODS: 28,711 vouchers were
      distributed to adolescents in disadvantaged areas of Managua that gave free-of
      charge access to SRH care in 4 public, 10 non-governmental and 5 private clinics.
      Providers received training and guidelines, treatment protocols, and financial
      incentives for each adolescent attended. All clinics were visited by female
      adolescent SPs requesting contraception. SPs were sent one week before, during
      (with voucher) and one month after the intervention. After each consultation they
      were interviewed with a standardized questionnaire. Twenty-one criteria were
      scored and grouped into four categories. Clinics' scores were compared using non
      parametric statistical methods (paired design: before-during and before-after).
      Also the influence of doctors' characteristics was tested using non-parametric
      statistical methods. RESULTS: Some aspects of service quality improved during the
      voucher program. Before the program started 8 of the 16 SPs returned 'empty
      handed', although all were eligible contraceptive users. During the program 16/17
      left with a contraceptive method (p = 0.01). Furthermore, more SPs were involved
      in the contraceptive method choice (13/17 vs.5/16, p = 0.02). Shared decision
      making on contraceptive method as well as condom promotion had significantly
      increased after the program ended. Female doctors had best scores before- during
      and after the intervention. The improvements were more pronounced among male
      doctors and doctors older than 40, though these improvements did not sustain
      after the program ended. CONCLUSION: This study illustrates provider-related
      obstacles adolescents often face when requesting contraception. The care provided
      during the voucher program improved for some important outcomes. The improvements
      were more pronounced among providers with the weakest initial performance. Shared
      decision-making and condom promotion were improvements that sustained after the
      program ended. The SP method is suitable and relatively easy to apply in
      monitoring clinics' performance, yielding important and relevant information.
      Objective assessment of change through the SP method is much more complex and
      expensive.

PMID- 16893464
TI  - Epstein-Barr virus (EBV) detection and typing by PCR: a contribution to
      diagnostic screening of EBV-positive Burkitt's lymphoma.
AB  - BACKGROUND: Epstein-Barr virus (EBV) is associated to the etio-pathogenesis of an
      increasing number of tumors. Detection of EBV in pathology samples is relevant
      since its high prevalence in some cancers makes the virus a promising target of
      specific therapies. RNA in situ hybridization (RISH) is the standard diagnostic
      procedure, while polymerase chain reaction (PCR)-based methods are used for
      strain (EBV type-1 or 2) distinction. We performed a systematic comparison
      between RISH and PCR for EBV detection, in a group of childhood B-cell Non
      Hodgkin lymphomas (NHL), aiming to validate PCR as a first, rapid method for the
      diagnosis of EBV-associated B-cell NHL. METHODS: EBV infection was investigated
      in formalin fixed paraffin-embedded tumor samples of 41 children with B-cell NHL,
      including 35 Burkitt's lymphoma (BL), from Rio de Janeiro, Brazil, by in situ
      hybridization of EBV-encoded small RNA (EBER-RISH) and PCR assays based on EBNA2
      amplification. RESULTS: EBV genomes were detected in 68% of all NHL. Type 1 and 2
      accounted for 80% and 20% of EBV infection, respectively. PCR and RISH were
      highly concordant (95%), as well as single- and nested-PCR results, allowing the
      use of a single PCR round for diagnostic purposes. PCR assays showed a
      sensitivity and specificity of 96% and 100%, respectively, with a detection level
      of 1 EBV genome in 5,000-10,000 EBV-negative cells, excluding the possibility of
      detecting low-number EBV-bearing memory cells. CONCLUSION: We describe adequate
      PCR conditions with similar sensitivity and reliability to RISH, to be used for
      EBV diagnostic screening in high grade B-NHL, in "at risk" geographic regions.

PMID- 16893465
TI  - Automatic document classification of biological literature.
AB  - BACKGROUND: Document classification is a wide-spread problem with many
      applications, from organizing search engine snippets to spam filtering. We
      previously described Textpresso, a text-mining system for biological literature,
      which marks up full text according to a shallow ontology that includes terms of
      biological interest. This project investigates document classification in the
      context of biological literature, making use of the Textpresso markup of a corpus
      of Caenorhabditis elegans literature. RESULTS: We present a two-step text
      categorization algorithm to classify a corpus of C. elegans papers. Our
      classification method first uses a support vector machine-trained classifier,
      followed by a novel, phrase-based clustering algorithm. This clustering step
      autonomously creates cluster labels that are descriptive and understandable by
      humans. This clustering engine performed better on a standard test-set (Reuters
      21578) compared to previously published results (F-value of 0.55 vs. 0.49), while
      producing cluster descriptions that appear more useful. A web interface allows
      researchers to quickly navigate through the hierarchy and look for documents that
      belong to a specific concept. CONCLUSION: We have demonstrated a simple method to
      classify biological documents that embodies an improvement over current methods.
      While the classification results are currently optimized for Caenorhabditis
      elegans papers by human-created rules, the classification engine can be adapted
      to different types of documents. We have demonstrated this by presenting a web
      interface that allows researchers to quickly navigate through the hierarchy and
      look for documents that belong to a specific concept.

PMID- 16893466
TI  - UniFrac--an online tool for comparing microbial community diversity in a
      phylogenetic context.
AB  - BACKGROUND: Moving beyond pairwise significance tests to compare many microbial
      communities simultaneously is critical for understanding large-scale trends in
      microbial ecology and community assembly. Techniques that allow microbial
      communities to be compared in a phylogenetic context are rapidly gaining
      acceptance, but the widespread application of these techniques has been hindered
      by the difficulty of performing the analyses. RESULTS: We introduce UniFrac, a
      web application available at http://bmf.colorado.edu/unifrac, that allows several
      phylogenetic tests for differences among communities to be easily applied and
      interpreted. We demonstrate the use of UniFrac to cluster multiple environments,
      and to test which environments are significantly different. We show that analysis
      of previously published sequences from the Columbia river, its estuary, and the
      adjacent coastal ocean using the UniFrac interface provided insights that were
      not apparent from the initial data analysis, which used other commonly employed
      techniques to compare the communities. CONCLUSION: UniFrac provides easy access
      to powerful multivariate techniques for comparing microbial communities in a
      phylogenetic context. We thus expect that it will provide a completely new
      picture of many microbial interactions and processes in both environmental and
      medical contexts.

PMID- 16893467
TI  - Clear cell sarcoma of the scapula. A case report and review of the literature.
AB  - BACKGROUND: Clear cell sarcoma of tendons and aponeuroses (CCSTA) appears usually
      in the extremities and rarely in the trunk. CASE PRESENTATION: We present an
      unusual case of CCSTA overlying the scapular region and with secondary osseous
      extension in the lower scapula. The patient underwent a wide local excision with
      removal of the tumor and the lower two thirds of the scapula. He had no local
      recurrences but he developed lung metastases after 5 months in spite of
      postoperative chemotherapy. He finally died ten months later. CONCLUSION: The
      patients with CCSTA have a variable unpredictable course. Despite treatment the
      overall prognosis is poor.

PMID- 16893468
TI  - Circumstances surrounding dying in the paediatric intensive care unit.
AB  - BACKGROUND: Death is inevitable in the paediatric intensive care unit (PICU). We
      aimed to describe the circumstances surrounding dying in a PICU. METHOD: The
      chart records of all patients less than 18 years of age who died at the PICU
      between January first 2000 and July first 2005 were retrospectively analyzed.
      Information regarding sex, age, length of stay, admission, diagnosis, and the way
      a patient died was registered. Post mortem information regarding natural versus
      unnatural death, autopsy and donation was obtained. Non-survivors were allocated
      in five groups: do-not-resuscitate (DNR), withholding and/or withdrawal of
      therapy (W/W), failed cardiopulmonary resuscitation (failed CPR), brain death
      (BD), and terminal organ failure (TOF). RESULTS: During the study period 87
      (4.4%) of the 1995 admitted patients died. Non-survivors were more often admitted
      during the day (54%) and the week (68%). W/W was found in 27.6%, TOF in 26.4%, BD
      in 23.0%, failed CPR in 18.4%, and DNR in 4.6%. Forty-three percent died in the
      first two days, of which BD (40.5%) and failed CPR (37.8%) were most common.
      Seventy-five children (86%) died due to a natural cause. Autopsy permission was
      obtained in 19 of 54 patients (35%). The autopsies confirmed the clinical
      diagnosis in 11 patients, revealed new information in 5 patients, and in 3
      patients the autopsy did not provide additional information. Nine patients were
      medically suitable for organ donation and 24 patients for tissue donation,
      whereas consent was only obtained in 2 cases in both groups. CONCLUSION: We
      observed that 43% of the patients died within the first two days of admission due
      to BD and failed CPR, whereas after 4 days most patients died after W/W. Autopsy
      remains an useful tool to confirm clinical diagnoses or to provide new
      information. Only a small percentage of the deceased children is suitable for
      organ donation.

PMID- 16893469
TI  - The chaperone DnaK controls the fractioning of functional protein between soluble
      and insoluble cell fractions in inclusion body-forming cells.
AB  - BACKGROUND: The molecular mechanics of inclusion body formation is still far from
      being completely understood, specially regarding the occurrence of properly
      folded, protein species that exhibit natural biological activities. We have here
      comparatively explored thermally promoted, in vivo protein aggregation and the
      formation of bacterial inclusion bodies, from both structural and functional
      sides. Also, the status of the soluble and insoluble protein versions in both
      aggregation systems have been examined as well as the role of the main molecular
      chaperones GroEL and DnaK in the conformational quality of the target
      polypeptide. RESULTS: While thermal denaturation results in the formation of
      heterogeneous aggregates that are rather stable in composition, protein
      deposition as inclusion bodies renders homogenous but strongly evolving
      structures, which are progressively enriched in the main protein species while
      gaining native-like structure. Although both type of aggregates display common
      features, inclusion body formation but not thermal-induced aggregation involves
      deposition of functional polypeptides that confer biological activity to such
      particles, at expenses of the average conformational quality of the protein
      population remaining in the soluble cell fraction. In absence of DnaK, however,
      the activity and conformational nativeness of inclusion body proteins are
      dramatically impaired while the soluble protein version gains specific activity.
      CONCLUSION: The chaperone DnaK controls the fractioning of active protein between
      soluble and insoluble cell fractions in inclusion body-forming cells but not
      during thermally-driven protein aggregation. This cell protein, probably through
      diverse activities, is responsible for the occurrence and enrichment in inclusion
      bodies of native-like, functional polypeptides, that are much less represented in
      other kind of protein aggregates.

PMID- 16893470
TI  - Mapping oral health related quality of life to generic health state values.
AB  - BACKGROUND: A summary utility index is useful for deriving quality-adjusted life
      years (QALY) for cost analyses or disability weights for burden of disease
      studies. However, many quality of life instruments provide descriptive profiles
      rather than a single utility index. Transforming quality of life instruments to a
      utility index could extend the use of quality of life instruments to costs
      analyses and burden of disease studies. The aims of the study were to map a
      specific oral health measure, the Oral Health Impact Profile to a generic health
      state measure, the EuroQol, in order to enable the estimation of health state
      values based on OHIP data. METHODS: Data were collected from patients treated by
      a random sample of South Australian dentists in 2001-02 using mailed self
      complete questionnaires. Dentists recorded the diagnosis of dental conditions and
      provided patients with self-complete questionnaires to record the nature,
      severity and duration of symptoms using the EuroQol (EQ-5D) and 14-item version
      of the Oral Health Impact Profile (OHIP-14) instruments. Data were available from
      375 patients (response rate = 72%). A random two-thirds sample of patients was
      used in tobit regressions of EQ-5D health state values estimated using OHIP-14 in
      a model with categories of OHIP responses as indicator variables and in a model
      with OHIP responses as continuous variables. Age and sex were included as
      covariates in both models. The remaining one-third sample of patients was used to
      test the models. RESULTS: The OHIP item 'painful aching in mouth' was
      significantly related to health state values in both models while 'life less
      satisfying' was also significant in the continuous model. Mean forecast errors
      relative to the mean observed health state value were higher when fitted to the
      categorical model (17.4%) compared to the continuous model (15.2%) (P < 0.05).
      CONCLUSION: The findings enable health state values to be derived from OHIP-14
      scores for populations where utility has not or cannot be measured directly.

PMID- 16893472
TI  - Burden of premature mortality in rural Vietnam from 1999-2003: analyses from a
      Demographic Surveillance Site.
AB  - BACKGROUND: Assessing the burden of disease contributes towards evidence-based
      allocation of limited health resources. However, such measures are not yet
      commonly available in Vietnam. Taking advantage of the FilaBavi Demographic
      Surveillance Site (FilaBavi DSS) in Vietnam, this study aimed to establish the
      feasibility of applying the Years of Life Lost (YLL) technique in the context of
      a defined DSS, and to estimate the importance of the principal causes of
      premature mortality in a rural area of Vietnam between 1999 and 2003. METHODS:
      Global Burden of Disease methods were applied. Causes of death were ascertained
      by verbal autopsy. RESULTS: In five years, 1,240 deaths occurred and for 1,220
      cases cause of death information from verbal autopsy was available. Life
      expectancy at birth was 71.0 (95% confidence interval 69.9-72.1) in males and
      80.9 (79.9-81.9) in females. The discounted, but not age weighted YLL per 1,000
      population was 85 and 55 for males and females, respectively. The leading causes
      of YLL and death counts were cardiovascular diseases, malignant neoplasms,
      unintentional injuries, and neonatal causes. Males contributed 54% of total
      deaths and 59% of YLL. Males experienced higher YLL than women across all causes.
      Filabavi mortality estimates are considerably lower than 2002 WHO country
      estimates for Vietnam. Also the FilaBavi cause distribution varies considerably
      from the WHO result. CONCLUSION: The combination of localised demographic
      surveillance, verbal autopsy and the application of YLL methods enable new
      insights into the magnitude and importance of significant public health issues in
      settings where evidence for planning is otherwise scarce. Local mortality data
      vary considerably from the WHO model-based estimates.

PMID- 16893471
TI  - Nonassociative learning as gated neural integrator and differentiator in stimulus
      response pathways.
AB  - Nonassociative learning is a basic neuroadaptive behavior exhibited across animal
      phyla and sensory modalities but its role in brain intelligence is unclear.
      Current literature on habituation and sensitization, the classic "dual process"
      of nonassociative learning, gives highly incongruous accounts between varying
      experimental paradigms. Here we propose a general theory of nonassociative
      learning featuring four base modes: habituation/primary sensitization in primary
      stimulus-response pathways, and desensitization/secondary sensitization in
      secondary stimulus-response pathways. Primary and secondary modes of
      nonassociative learning are distinguished by corresponding activity-dependent
      recall, or nonassociative gating, of neurotransmission memory. From the
      perspective of brain computation, nonassociative learning is a form of integral
      differential calculus whereas nonassociative gating is a form of Boolean logic
      operator--both dynamically transforming the stimulus-response relationship. From
      the perspective of sensory integration, nonassociative gating provides temporal
      filtering whereas nonassociative learning affords low-pass, high-pass or band
      pass/band-stop frequency filtering--effectively creating an intelligent sensory
      firewall that screens all stimuli for attention and resultant internal model
      adaptation and reaction. This unified framework ties together many salient
      characteristics of nonassociative learning and nonassociative gating and suggests
      a common kernel that correlates with a wide variety of sensorimotor integration
      behaviors such as central resetting and self-organization of sensory inputs, fail
      safe sensorimotor compensation, integral-differential and gated modulation of
      sensorimotor feedbacks, alarm reaction, novelty detection and selective
      attention, as well as a variety of mental and neurological disorders such as
      sensorimotor instability, attention deficit hyperactivity, sensory defensiveness,
      autism, nonassociative fear and anxiety, schizophrenia, addiction and craving,
      pain sensitization and phantom sensations, etc.

PMID- 16893475
TI  - Repetitive DNA elements as mediators of genomic change in response to
      environmental cues.
AB  - There is no logical or theoretical barrier to the proposition that organismal and
      cell signaling could transduce environmental signals into specific, beneficial
      changes in primary structure of noncoding DNA via repetitive element movement or
      mutation. Repetitive DNA elements, including transposons and microsatellites, are
      known to influence the structure and expression of protein-coding genes, and to
      be responsive to environmental signals in some cases. These effects may create
      fodder for adaptive evolution, at rates exceeding those observed for point
      mutations. In many cases, the changes are no doubt random, and fitness is
      increased through simple natural selection. However, some transposons insert at
      specific sites, and certain regions of the genome exhibit selectively and
      beneficially high mutation rates in a range of organisms. In multicellular
      organisms, this could benefit individuals in situations with significant
      potential for clonal expansion: early life stages or regenerative tissues in
      animals, and most plant tissues. Transmission of the change to the next
      generation could occur in plants and, under some circumstances, in animals.

PMID- 16893474
TI  - Elastic fibres in health and disease.
AB  - Elastic fibres are a major class of extracellular matrix fibres that are abundant
      in dynamic connective tissues such as arteries, lungs, skin and ligaments. Their
      structural role is to endow tissues with elastic recoil and resilience. They also
      act as an important adhesion template for cells, and they regulate growth factor
      availability. Mutations in major structural components of elastic fibres,
      especially elastin, fibrillins and fibulin-5, cause severe, often life
      threatening, heritable connective tissue diseases such as Marfan syndrome,
      supravalvular aortic stenosis and cutis laxa. Elastic-fibre function is also
      frequently compromised in damaged or aged elastic tissues. The ability to
      regenerate or engineer elastic fibres and tissues remains a significant
      challenge, requiring improved understanding of the molecular and cellular basis
      of elastic-fibre biology and pathology, and ability to regulate the
      spatiotemporal expression and assembly of its molecular components.

PMID- 16893473
TI  - Identification of differentially expressed genes in cutaneous squamous cell
      carcinoma by microarray expression profiling.
AB  - BACKGROUND: Carcinogenesis is a multi-step process indicated by several genes up-
      or down-regulated during tumor progression. This study examined and identified
      differentially expressed genes in cutaneous squamous cell carcinoma (SCC).
      RESULTS: Three different biopsies of 5 immunosuppressed organ-transplanted
      recipients each normal skin (all were pooled), actinic keratosis (AK) (two were
      pooled), and invasive SCC and additionally 5 normal skin tissues from
      immunocompetent patients were analyzed. Thus, total RNA of 15 specimens were used
      for hybridization with Affymetrix HG-U133A microarray technology containing
      22,283 genes. Data analyses were performed by prediction analysis of microarrays
      using nearest shrunken centroids with the threshold 3.5 and ANOVA analysis was
      independently performed in order to identify differentially expressed genes (p <
      0.05). Verification of 13 up- or down-regulated genes was performed by
      quantitative real-time reverse transcription (RT)-PCR and genes were additionally
      confirmed by sequencing. Broad coherent patterns in normal skin vs. AK and SCC
      were observed for 118 genes. CONCLUSION: The majority of identified
      differentially expressed genes in cutaneous SCC were previously not described.

PMID- 16893476
TI  - Bird evolution in the Eocene: climate change in Europe and a Danish fossil fauna.
AB  - The pattern of the evolutionary radiation of modern birds (Neornithes) has been
      debated for more than 10 years. However, the early fossil record of birds from
      the Paleogene, in particular, the Lower Eocene, has only recently begun to be
      used in a phylogenetic context to address the dynamics of this major vertebrate
      radiation. The Cretaceous-Paleogene (K-P) extinction event dominates our
      understanding of early modern bird evolution, but climate change throughout the
      Eocene is known to have also played a major role. The Paleocene and Lower Eocene
      was a time of avian diversification as a result of favourable global climatic
      conditions. Deteriorations in climate beginning in the Middle Eocene appear to be
      responsible for the demise of previously widespread avian lineages like
      Lithornithiformes and Gastornithidae. Other groups, such as Galliformes display
      replacement of some lineages by others, probably related to adaptations to a
      drier climate. Finally, the combination of slowly deteriorating climatic
      conditions from the Middle Eocene onwards, appears to have slowed the
      evolutionary rate in Europe, as avian faunas did not differentiate markedly until
      the Oligocene. Taking biotic factors in tandem with the known Paleogene fossil
      record of Neornithes has recently begun to illuminate this evolutionary event.
      Well-preserved fossil taxa are required in combination with ever-improving
      phylogenetic hypotheses for the inter-relationships of modern birds founded on
      morphological characters. One key avifauna of this age, synthesised for the first
      time herein, is the Lower Eocene Fur Formation of Denmark. The Fur birds
      represent some of the best preserved (often in three dimensions and with soft
      tissues) known fossil records for major clades of modern birds. Clear
      phylogenetic assessment of these fossils will prove critical for future
      calibration of the neornithine evolutionary timescale. Some early diverging
      clades were clearly present in the Paleocene as evidenced directly by new fossil
      material alongside the phylogenetically constrained Lower Eocene taxa. A later
      Oligocene radiation of clades other than Passeriformes is not supported by
      available fossil data.

PMID- 16893477
TI  - Mechanism of peptide bond formation on the ribosome.
AB  - Peptide bond formation is the fundamental reaction of ribosomal protein
      synthesis. The ribosome's active site--the peptidyl transferase center--is
      composed of rRNA, and thus the ribosome is the largest known RNA catalyst. The
      ribosome accelerates peptide bond formation by 10(7)-fold relative to the
      uncatalyzed reaction. Recent progress of structural, biochemical and
      computational approaches has provided a fairly detailed picture of the catalytic
      mechanisms employed by the ribosome. Energetically, catalysis is entirely
      entropic, indicating an important role of solvent reorganization, substrate
      positioning, and/or orientation of the reacting groups within the active site.
      The ribosome provides a pre-organized network of electrostatic interactions that
      stabilize the transition state and facilitate proton shuttling involving ribose
      hydroxyl groups of tRNA. The catalytic mechanism employed by the ribosome
      suggests how ancient RNA-world enzymes may have functioned.

PMID- 16893478
TI  - Oxcarbazepine for self-mutilating bulimic patients.

PMID- 16893479
TI  - Platelet 5-HT2A receptor subresponsivity and lethality of attempted suicide in
      depressed in-patients.
AB  - In depressed patients, high-lethality suicidal acts are accompanied by serotonin
      system abnormalities analogous to those seen in completed suicides. We have
      previously reported greater platelet 5-HT2A receptor density, and impaired
      serotonin enhancement of ADP-induced platelet aggregation, an indirect measure of
      signal transduction, in high-lethality suicide attempters. We hypothesized that
      serotonin-activated phosphoinositide (PI) hydrolysis, a direct measure of
      platelet serotonin 5-HT2A receptor responsivity would be lower in depressed high
      lethality suicide attempters. Twenty-three depressed in-patients that had
      previously made suicide attempts (low-lethality, n=6; high-lethality, n=17) had
      platelet 5-HT2A-mediated serotonin-simulated PI hydrolysis assayed. Platelet 5
      HT2A receptor responsivity in high-lethality suicide attempters was 41% that of
      low-lethality suicide attempters (p<0.05). A seasonal effect was also observed.
      High-lethality suicidal acts are associated with more 5-HT2A receptors but
      impaired signal transduction.

PMID- 16893480
TI  - Relationship between drug company funding and outcomes of clinical psychiatric
      research.
AB  - BACKGROUND: Pharmaceutical industry funding of psychiatric research has increased
      significantly in recent decades, raising the question of a relationship between
      pharmaceutical company funding of clinical psychiatric studies and the outcomes
      of those studies. This study examines this relationship. METHOD: Abstracts of
      articles from 1992 and 2002 in four peer-reviewed psychiatric journals were
      examined. Drug outcomes (n=542) for clinical studies were evaluated and then
      compared across sponsorship source. Outcome raters were blind to source of
      sponsorship. The percentage of these studies sponsored by drug companies in 2002
      v. 1992 was also compared. In a secondary analysis, the contribution of a series
      of potentially mediating variables to the relationship between sponsorship source
      and study outcome was assessed via logistic regression. RESULTS: The percentage
      of studies sponsored by drug companies increased from 25% in 1992 to 57% in 2002.
      Favorable outcomes were significantly more common in studies sponsored by the
      drug manufacturer (78%) than in studies without industry sponsorship (48%) or
      sponsored by a competitor (28%). These relationships remained after controlling
      for the effects of journal, year, drug studied, time since FDA drug approval,
      diagnosis, sample size, and selected study design variables. CONCLUSIONS: These
      data indicate an association between pharmaceutical industry funding of clinical
      studies and positive outcomes of those studies. Further research is needed to
      elucidate the mechanisms underlying this relationship.

PMID- 16893481
TI  - Dimensional representations of DSM-IV cluster A personality disorders in a
      population-based sample of Norwegian twins: a multivariate study.
AB  - BACKGROUND: The 'odd' or 'Cluster A' personality disorders (PDs) - paranoid,
      schizoid and schizotypal PDs - were created in DSM-III with little empirical
      foundation. We have examined the relationship between the genetic and
      environmental risk factors for dimensional representations of these three
      personality disorders. METHOD: These personality disorders were assessed using
      the Structured Interview for DSM-IV Personality (SIDP-IV) in 1386 young adult
      twin pairs from the Norwegian Institute of Public Health Twin Panel. Using Mx, a
      single-factor independent pathway twin model was fitted to the number of endorsed
      criteria for the three disorders. RESULTS: The best-fit model included genetic
      and unique environmental common factors and genetic and unique environmental
      effects specific to each personality disorder. Total heritability was modest for
      these personality disorders and ranged from 21% to 28%. Loadings on the common
      genetic and unique environmental factors were substantially higher for
      schizotypal than for paranoid or schizoid PD. The proportion of genetic liability
      shared with all Cluster A disorders was estimated at 100, 43 and 26% respectively
      for schizotypal, paranoid and schizoid PDs. CONCLUSION: In support of the
      validity of the Cluster A construct, dimensional representations of schizotypal,
      paranoid and schizoid PD are all modestly heritable and share a portion of their
      genetic and environmental risk factors. No evidence was found for shared
      environmental or sex effects for these PDs. Schizotypal PD most closely reflects
      the genetic and environmental liability common to all three Cluster A disorders.
      These results should be interpreted in the context of the limited power of this
      sample.

PMID- 16893482
TI  - Caffeine intake, toxicity and dependence and lifetime risk for psychiatric and
      substance use disorders: an epidemiologic and co-twin control analysis.
AB  - BACKGROUND: Although caffeine is the most commonly used psychoactive substance
      and often produces symptoms of toxicity and dependence, little is known,
      especially in community samples, about the association between caffeine use,
      toxicity and dependence and risk for common psychiatric and substance use
      disorders. METHOD: Assessments of lifetime maximal caffeine use and symptoms of
      caffeine toxicity and dependence were available on over 3600 adult twins
      ascertained from the population-based Virginia Twin Registry. Lifetime histories
      of major depression (MD), generalized anxiety disorder (GAD) and panic disorder,
      alcohol dependence, adult antisocial behavior and cannabis and cocaine
      abuse/dependence were obtained at personal interview. Logistic regression
      analyses in the entire sample and within monozygotic (MZ) twin pairs were
      conducted in SAS. RESULTS: In the entire sample, measures of maximal caffeine
      use, heavy caffeine use, and caffeine-related toxicity and dependence were
      significantly and positively associated with all seven psychiatric and substance
      use disorders. However, within MZ twin pairs, controlling for genetic and family
      environmental factors, these associations, while positive, were all non
      significant. These results were similar when excluding twins who denied regular
      caffeine use. CONCLUSIONS: Maximal lifetime caffeine intake and caffeine
      associated toxicity and dependence are moderately associated with risk for a wide
      range of psychiatric and substance use disorders. Analyses of these relationships
      within MZ twin pairs suggest that most of the observed associations are not
      causal. Rather, familial factors, which are probably in part genetic, predispose
      to both caffeine intake, toxicity and dependence and the risk for a broad array
      of internalizing and externalizing disorders.

PMID- 16893483
TI  - Face affect recognition deficits in personality-disordered offenders: association
      with psychopathy.
AB  - BACKGROUND: There is a limited literature examining face affect recognition in
      offenders. In line with the Integrated Emotion Systems (IES) model, existing
      studies suggest a psychopathy-related deficit in sad/fear recognition. However,
      many of these studies have small samples, and few include a healthy control group
      in order to examine the contribution of criminality. METHOD: We compared the
      performance of male criminals with dissocial (antisocial) personality disorder
      (PD group) and healthy male IQ-matched controls, on a morphed face affect
      processing task and examined the relationship between psychopathy (assessed using
      the Psychopathy Checklist: Screening Version, PCL: SV), score and performance on
      this task in the PD sample. RESULTS: The PD group had a specific deficit in the
      recognition of sad facial affect that was present even at 100% expression
      intensity. This deficit could not be attributed to impulsive responding as the PD
      group generally had longer mean reaction times than healthy controls. Within the
      PD group, those with high scores on the PCL: SV were less accurate than low
      scorers at classifying sad facial affect. There was also a significant negative
      correlation between total psychopathy score and sad affect recognition accuracy.
      There were no specific relationships between affect recognition and the
      subcomponents of psychopathy. CONCLUSIONS: The findings suggest that
      criminality/antisocial personality may be associated with a deficit in the
      recognition of aversive cues in others, and that this deficit is more severe in
      psychopathic offenders. The findings lend further support to the IES model.

PMID- 16893484
TI  - Potential microbiological contamination of effluents in poultry and swine
      abattoirs.
AB  - Health risks in the effluents of seven swine abattoirs and of seven poultry
      abattoirs were evaluated with regard to environment degradation and to
      dissemination of pathogenic microorganisms during the rainy and dry seasons.
      Supply-water samples from affluents and effluents of the treatment systems at
      different sites within the abattoir processing system were analysed. Similarly,
      water samples from the three recipient sites (emission point, 100 m upstream, 100
      m downstream) were also analysed. Temperature, free residual chlorine (FRC),
      total coliform bacteria, Escherichia coli, enterococci, identification and
      serotyping of salmonellae were assessed. Scalding is the most significant stage
      in the slaughtering chain (P<0.05) when temperature is taken into account.
      Temperatures at effluents and at the sampled sites in the water bodies accorded
      to state and federal legislation standards. Supply waters did not meet the
      standards for FRC and microbial count standards according to the Ministry of
      Health and within limits imposed by the Industrial and Sanitary Inspection
      Regulations for Animal Products. Feather plucking and evisceration in poultry
      slaughter and the cleansing of carcasses and facilities in poultry and swine
      slaughtering had the highest contamination impact. The three loci at the water
      bodies were above the microbiological standards for classes II and III sites, in
      conformity with Law 8468 of the state of Sao Paulo, Brazil and Conama. Salmonella
      was found at several sites during slaughter, at both types of abattoirs,
      including in the effluent treatment system. This showed that these sites were the
      dissemination sources of the microorganism.

PMID- 16893485
TI  - Discernment between deliberate and natural infectious disease outbreaks.
AB  - Public health authorities should be vigilant to the potential for outbreaks
      deliberately caused by biological agents (bioterrorism). Such events require a
      rapid response and incorporation of non-traditional partners for disease
      investigation and outbreak control. The astute application of infectious disease
      epidemiological principles can promote an enhanced index of suspicion for such
      events. We discuss epidemiological indicators that should be considered during
      outbreak investigations, and also examine their application during bioterrorism
      incidents, an accidental release of an agent, outbreaks of infections that were
      alleged to have been deliberately initiated, and a model scenario. The Grunow &
      Finke epidemiological assessment tool is used to examine these historical events
      and the model scenario. The results received from this analysis, coupled with an
      understanding of epidemiological clues to unnatural events, and knowledge of how
      to manage such events, can aid in the improved response and resolution of
      epidemics.

PMID- 16893487
TI  - Possible ecology and epidemiology of medically important mosquito-borne
      arboviruses in Great Britain.
AB  - Nine different arboviruses are known to be transmitted by, or associated with,
      mosquitoes in Europe, and several (West Nile, Sindbis and Tahyna viruses) are
      reported to cause outbreaks of human disease. Although there have been no
      reported human cases in Great Britain (GB), there have been no published in-depth
      serological surveys for evidence of human infection. This paper investigates the
      ecological and entomological factors that could influence or restrict
      transmission of these viruses in GB, suggesting that in addition to West Nile
      virus, Sindbis and Tahyna viruses could exist in enzootic cycles, and that
      certain ecological factors could facilitate transmission to humans. However, the
      level of transmission is likely to be lower than in endemic foci elsewhere in
      Europe due to key ecological differences related to spatial and temporal dynamics
      of putative mosquito vectors and presence of key reservoir hosts. Knowledge of
      the potential GB-specific disease ecology can aid assessments of risk from
      mosquito-borne arboviruses.

PMID- 16893486
TI  - Hepatitis C virus infection among injecting drug users in Scotland: a review of
      prevalence and incidence data and the methods used to generate them.
AB  - It is estimated that of 50,000 persons in Scotland (1% of the county's
      population), infected with the hepatitis C virus (HCV), around 90% injected
      drugs. This paper reviews data on the prevalence and incidence of HCV, and the
      methods used to generate such information, among injecting drug users (IDUs), in
      Scotland. The prevalence estimate for HCV among IDUs in Scotland as a whole (44%
      in 2000), is comparable with those observed in many European countries. Incidence
      rates ranged from 11.9 to 28.4/100 person-years. The data have shaped policy to
      prevent infection among IDUs and have informed predictions of the number of HCV
      infected IDUs who will likely progress to, and require treatment and care for,
      severe HCV-related liver disease. Although harm reduction interventions, in
      particular needle and syringe exchanges and methadone maintenance therapy,
      reduced the transmission of HCV among IDUs during the early to mid-1990s,
      incidence in many parts of the country remains high. The prevention of HCV among
      IDUs continues to be one of Scotland's major public health challenges.

PMID- 16893488
TI  - Estimation of European wild boar relative abundance and aggregation: a novel
      method in epidemiological risk assessment.
AB  - Wild boars are important disease reservoirs. It is well known that abundance
      estimates are needed in wildlife epidemiology, but the expense and effort
      required to obtain them is prohibitive. We evaluated a simple method based on the
      frequency of faecal droppings found on transects (FBII), and developed a spatial
      aggregation index, based on the runs test statistic. Estimates were compared with
      hunting data, and with porcine circovirus and Aujeszky's disease virus
      seroprevalences and Mycobacterium tuberculosis complex and Metastrongylus spp.
      prevalence. The FBII and the aggregation index were correlated with the hunting
      index, but both of the former estimates correlated better than the latter with
      the disease prevalences. Hence, at least in habitats with high wild boar
      densities, the FBII combined with the aggregation index constitutes a cheap and
      reliable alternative for wild boar abundance estimation that can be used for
      epidemiological risk assessment, even outside the hunting season and in areas
      with no available data on hunting activities.

PMID- 16893489
TI  - The Lyme vaccine: a cautionary tale.
AB  - People living in endemic areas acquire Lyme disease from the bite of an infected
      tick. This infection, when diagnosed and treated early in its course, usually
      responds well to antibiotic therapy. A minority of patients develops more serious
      disease, particularly after a delay in diagnosis or therapy, and sometimes
      chronic neurological, cardiac, or rheumatological manifestations. In 1998, the
      FDA approved a new recombinant Lyme vaccine, LYMErix, which reduced new
      infections in vaccinated adults by nearly 80%. Just 3 years later, the
      manufacturer voluntarily withdrew its product from the market amidst media
      coverage, fears of vaccine side-effects, and declining sales. This paper reviews
      these events in detail and focuses on the public communication of risks and
      benefits of the Lyme vaccine and important lessons learned.

PMID- 16893490
TI  - Risk factors for typhoid fever in a slum in Dhaka, Bangladesh.
AB  - We systematically investigated risk factors for typhoid fever in Kamalapur, a
      poor urban area of Bangladesh, to inform targeted public health measures for its
      control. We interviewed patients with typhoid fever and two age-matched controls
      per case about exposures during the 14 days before the onset of illness. The
      municipal water supply was used by all 41 cases and 81of 82 controls. In
      multivariate analysis, drinking unboiled water at home was a significant risk
      factor [adjusted odds ratio (aOR) 12.1, 95% CI 2.2-65.6]. Twenty-three (56%)
      cases and 21 (26%) controls reported that water from the primary source was foul
      smelling (aOR 7.4, 95% CI 2.1-25.4). Eating papaya was associated with illness
      (aOR 5.2, 95% CI 1.2-22.2). Using a latrine for defecation was significantly
      protective (aOR 0.1, 95% CI 0.02-0.9). Improved chlorination of the municipal
      water supply or disinfecting drinking water at the household level may
      dramatically reduce the risk of typhoid fever in Kamalapur. The protective effect
      of using latrines, particularly among young children, should be investigated
      further.

PMID- 16893492
TI  - Does atypical antipsychotic medication improve executive function in
      schizophrenia?

PMID- 16893496
TI  - CD40/CD40L dyad in the inflammatory and immune responses in the central nervous
      system.
AB  - CD40 and its cognate ligand (CD40L) are a pair of regulators of pro-inflammatory
      and immune responses. In the central nervous system (CNS), CD40 is expressed on a
      variety of cells, including vascular endothelial cells, smooth muscle cells,
      astrocytes and microglia (the brain macrophages, being the most sensitive cell
      type to respond to CD40 ligand). Interaction between CD40 on microglia and CD40L
      presented by infiltrating T lymphocytes and other resident CNS cells triggers a
      series of intracellular signaling events that promote the production of a wide
      array of cytokines, chemokines and neurotoxins. Thus, both molecules serve as
      amplifiers of pro-inflammatory and immune responses in the CNS and constitute
      important molecular targets for therapeutic intervention of diseases.

PMID- 16893493
TI  - The effects of acute tryptophan depletion and serotonin transporter polymorphism
      on emotional processing in memory and attention.
AB  - Polymorphism at the serotonin transporter linked polymorphic region (5-HTTLPR)
      has been associated with neuroticism, increased risk for affective disorders and
      greater vulnerability to mood change following serotonin (5-HT) depletion. The
      aim of the present study was to investigate whether the cognitive effects of 5-HT
      depletion were differentially affected by genotype at the 5-HTTLPR polymorphism,
      using neuropsychological measures of memory and attention. We utilized the acute
      tryptophan depletion (ATD) technique to temporarily reduce 5-HT synthesis in two
      groups of healthy volunteers pre-selected on the basis of 5-HTTLPR genotype, 15
      of the ll genotype and 15 of the ss genotype, in a double-blind, placebo
      controlled crossover design. As expected, ATD resulted in a robust reduction in
      plasma tryptophan concentration in both genotype groups. However, the genotype
      groups differed in terms of the effect of ATD on cognitive performance. The ss
      genotype group showed impaired verbal recall following depletion, while episodic
      memory was unimpaired by ATD in the ll genotype group. Averaging across depletion
      condition, the ss genotype group outperformed the ll genotype group on tests of
      episodic memory and attention. Neither group was significantly affected by ATD on
      measures of emotional state. These data confirm previous reports that ss
      individuals are particularly vulnerable to 5-HT depletion, but extend these
      findings to the cognitive domain. The unexpected finding that ss volunteers
      showed improved memory and attention relative to ll volunteers suggests a
      possible evolutionary advantage to possession of the s allele, which may offset
      the disadvantage of vulnerability to depression following stressful life events.

PMID- 16893495
TI  - Mortality in a cohort of chronically fatigued patients.
AB  - BACKGROUND: Comprehensive studies of mortality among patients with chronic
      fatigue (CF) and chronic fatigue syndrome (CFS) have not been published, but
      several sources suggest that CFS is associated with an elevated risk for suicide.
      METHOD: Data on 1201 chronically fatigued patients followed in a university
      affiliated tertiary-care clinic for up to 14 years were submitted to the Center
      for Disease Control and Prevention (CDC) National Death Index (NDI) to evaluate
      all-cause and suicide-caused death rates against standardized mortality rates
      (SMRs). We used Life Table Analysis to examine the influence of sex and diagnoses
      of CFS and depression. RESULTS: All-cause mortality in chronically fatigued
      patients was no higher than expected, but suicide-caused death rates were more
      than eight times higher than in the US general population. The significant
      elevation in the SMR of suicide was restricted to those who did not meet criteria
      for CFS [SMR(CF)=14.2, 95% confidence interval (CI) 5.7-29.3 versus SMR(CFS)=3.6,
      95% CI 0.4-12.9]. Among chronically fatigued patients who did not meet CFS
      criteria, those with a lifetime history of major depression (MD) had higher
      suicide-caused death rates than among their non-depressed counterparts
      (SMR(MD)=19.1, 95% CI 7.0-41.5 versus SMR(NMD)=5.6, 95% CI 0.1-31.4), although
      the difference was not significant. CONCLUSIONS: CFS does not appear to be
      associated with increased all-cause mortality or suicide rates. Clinicians,
      however, should carefully evaluate patients with CF for depression and
      suicidality.

PMID- 16893497
TI  - The mechanism of organophosphorus pesticide-induced inhibition of cytolytic
      activity of killer cells.
AB  - The main toxicity of organophosphorus pesticides (OPs) is neurotoxicity, which is
      caused by the inhibition of acetylcholinesterase. OPs also affect immune
      responses including effects on antibody production, IL-2 production, T cell
      proliferation, decrease of CD5 cells, and increase of CD26 cells and
      autoantibodies. However, there have been few papers investigating the mechanism
      of OP-induced inhibition of cytolytic activity of killer cells. This study
      reviews the new mechanism of OP-induced inhibition of activities of natural
      killer (NK), lymphokine-activated killer (LAK) and cytotoxic T lymphocytes (CTL).
      NK, LAK and CTL induce cell death in tumor or virus-infected target cells by two
      main mechanisms. The first mechanism is direct release of cytolytic granules that
      contain perforin, granzymes, and granulysin by exocytosis to kill target cells,
      which is called the granule exocytosis pathway. The second mechanism is mediated
      by the Fas ligand (Fas-L)/Fas pathway. To date, it has been reported that OPs
      inhibit NK, LAK and CTL activities by at least the following three mechanisms: 1)
      OPs impair the granule exocytosis pathway of NK, LAK and CTL cells by inhibiting
      the activity of granzymes, and by decreasing the intracellular level of perforin,
      granzyme A and granulysin, which was mediated by inducing degranulation of NK
      cells and by inhibiting the transcript of mRNA of perforin, granzyme A and
      granulysin; 2) OPs impair the FasL/Fas pathway of NK, LAK and CTL cells, as
      investigated by using perforin-knockout mice, in which the granule exocytosis
      pathway of NK cells does not function and only the FasL/Fas pathway remains
      functional; 3) OPs induce apoptosis of immune cells.

PMID- 16893499
TI  - The phenotypic characterization of naturally occurring regulatory CD4+CD25+ T
      cells.
AB  - The homeostasis of the immune system depends on the balance between the immune
      response to an invaded pathogen and the immune tolerance to self antigens. Both
      central and peripheral tolerances are important mechanisms for the induction and
      maintenance of T cell tolerance. Recently, much attention has been paid to
      regulatory T cells (Treg), which play a significant role in maintaining
      peripheral immune tolerance. So far, there has been no satisfactory advance
      regarding the surface markers of Treg cells, as none is unique for Treg cells. In
      this review, we summarize some important molecules expressed in naturally
      occurring CD4+CD25+ Treg cells (nTreg), including forkhead/winged-helix family
      transcriptional repressor p3 (Foxp3), the tumor necrosis factor receptor (TNFR)
      family, CD28/CTLA4 molecules, chemokine receptors, Toll-like receptors (TLRs),
      membrane-bound TGF-beta and other molecules, such as neuropilin-1, lymphocyte
      activation gene-3 (LAG)-3 and granzyme. This review provides a collective view on
      current studies of nTreg cell activation and development related to the
      expression of molecules and cell phenotype markers, which is important for
      elucidation of nTreg cell origin, development and function.

PMID- 16893500
TI  - Dendritic cell as therapeutic vaccines against tumors and its role in therapy for
      hepatocellular carcinoma.
AB  - Dendritic cells (DCs) are the most potent professional antigen-presenting cells,
      and capable of stimulating naive T cells and driving primary immune responses.
      DCs are poised to capture antigen, migrate to draining lymphoid organs, and after
      a process of maturation, select antigen-specific lymphocytes to which they
      present the processed antigen, thereby inducing immune responses. The development
      of protocols for the ex vivo generation of DCs may provide a rationale for
      designing and developing DC-based vaccination for the treatment of tumors. There
      are now several strategies being applied to upload antigens to DCs and manipulate
      DC vaccines. DC vaccines are able to induce therapeutic and protective antitumor
      immunity. Numerous studies indicated that hepatocellular carcinoma (HCC)
      immunotherapies utilizing DC-presenting tumor-associated antigens could stimulate
      an antitumour T cell response leading to clinical benefit without any significant
      toxicity. DC-based tumor vaccines have become a novel immunoadjuvant therapy for
      HCC.

PMID- 16893501
TI  - Dendritic cell-derived exosomes stimulate stronger CD8+ CTL responses and
      antitumor immunity than tumor cell-derived exosomes.
AB  - Exosomes (EXO) derived from dendritic cells (DC) and tumor cells have been used
      to stimulate antitumor immune responses in animal models and in clinical trials.
      However, there has been no side-by-side comparison of the stimulatory efficiency
      of the antitumor immune responses induced by these two commonly used EXO
      vaccines. In this study, we selected to study the phenotype characteristics of
      EXO derived from a transfected EG7 tumor cells expressing ovalbumin (OVA) and OVA
      pulsed DC by flow cytometry. We compared the stimulatory effect in induction of
      OVA-specific immune responses between these two types of EXO. We found that OVA
      protein-pulsed DCOVA-derived EXO (EXODC) can more efficiently stimulate naive OVA
      specific CD8+ T cell proliferation and differentiation into cytotoxic T
      lymphocytes in vivo, and induce more efficient antitumor immunity than EG7 tumor
      cell-derived EXO (EXOEG7). In addition, we elucidated the important role of the
      host DC in EXO vaccines that the stimulatory effect of EXO is delivered to T cell
      responses by the host DC. Therefore, DC-derived EXO may represent a more
      effective EXO-based vaccine in induction of antitumor immunity.

PMID- 16893498
TI  - Immunoregulatory role of B7-H1 in chronicity of inflammatory responses.
AB  - Pathogenesis of most chronic human diseases, including chronic infections,
      autoimmune diseases and cancers, often involves a persistent, unresolved
      inflammatory response. The molecular mechanisms that determine the conversion of
      an acute inflammatory response into a chronic process had puzzled researchers for
      many years. Recent studies reveal that B7-H1 (CD274, PD-L1), a newly identified
      co-stimulatory molecule, possesses dual functions of co-stimulation of naive T
      cells and inhibition of activated effector T cells. The aberrant cellular
      expression and deregulated function of B7-H1 have been reported during chronic
      viral and intracellular bacterial infection, as well as in many autoimmune
      diseases and cancers. Importantly, the deregulation of B7-H1's dual functions
      appears to be associated with a prolonged and incomplete immune response by
      luring naive T cells for activation and dampening activated effector T cells.
      Moreover, development of strategies targeting B7-H1 signals provides a new and
      promising approach to manipulate the devastating diseases associated with chronic
      inflammation. Thus, B7-H1 may play a critical immunoregulatory role in the
      chronicity of inflammatory responses.

PMID- 16893502
TI  - Valsartan inhibited the accumulation of dendritic cells in rat fibrotic renal
      tissue.
AB  - To observe the accumulation of dendritic cells (DCs) in rat remnant kidney and
      its contribution to tubulointerstitial fibrosis, under influence of valsartan on
      DCs, a rat remnant kidney model was established by subtotal nephrectomy. Four
      experimental groups were included: normal, sham, model (SNx) and the group
      treated with Valsartan (SNxV). Rats were killed at week 1, 4 and 12,
      respectively. CD1a+CD80+ DCs were assayed by double immunostaining method and the
      images were analyzed with Axioplan 2 microscopy. The expressions of P-selectin,
      TGF-beta1, alpha-SMA, collagen III and fibronectin was analyzed by
      immunohistochemistry or semi-quantitative RT-PCR, and the level of
      tubulointerstitial firosis (TIF) was scored. CD1a+CD80+ DCs were gradually
      increased among renal tubules, interstitium and vessels, especially in
      interstitium, and the number of DCs in model group at week 12 was much more than
      that in model groups at week 1 or 4. The expressions of P-selectin, TGF-beta1,
      alpha-SMA, collagen III and fibronectin in tubulointerstitial areas and the
      degree of TIF was increased substantially in model group at week 12. The
      accumulation of DCs in interstitium was well associated with the loss of renal
      function and the progression of tubulointerstitial fibrosis. Valsartan treatment
      inhibited the local accumulation of DCs and attenuated renal tubulointerstitial
      damage. The local DCs accumulation was related to tubulointerstitial fibrosis and
      renal dysfunction following renal ablation. Blockade to angiotensin II might be a
      potent way to attenuate renal immuno-inflammatory injury.

PMID- 16893504
TI  - Preliminary analysis of gene expression profiles in HepG2 cell line induced by
      different genotype core proteins of HCV.
AB  - In present investigation, we constructed recombinants expressing the HCV
      genotypes 1b, 2a, and 4d core proteins, and established human hepatocellular
      carcinoma (HepG2) cell line that expressed various genotype core proteins. The
      gene expression profiles in the cells expressing different HCV genotype core
      proteins were compared with those in the control by microarray analysis. In data
      analysis, a threshold was set to eliminate all genes that were not increased or
      decreased by 2.5-fold change in a comparison between the transfected cells and
      control cells. The preliminary microarray analysis suggests that the gene
      expression profiles regulated by three kinds of genotype core proteins are mainly
      involved in transport, signal transduction, regulation of transcription, protease
      activity, etc., and that some pathogenesis/oncogenesis gene expressions are
      up/down- regulated simultaneously in the HepG2 cell line. The data suggest that
      each core protein has its gene expressions profile and that the profiles are
      implicated in HCV replication and pathogenesis, which may open up a novel way to
      understand the function of the HCV variant core proteins biological and their
      pathogenic mechanism.

PMID- 16893503
TI  - Protection of mice from lethal endotoxemia by chimeric human BPI-Fcgamma1 gene
      delivery.
AB  - To evaluate the potentiality of applying gene therapy to endotoxemia in high-risk
      patients, we investigated the effects of transferring an adeno-associated virus
      serotype 2 (AAV2)-mediated BPI-Fcgamma1 gene on protecting mice from challenge of
      lethal endotoxin. The chimeric BPI-Fcgamma1 gene consists of two parts, one
      encods functional N-terminus (1 to 199 amino acidic residues) of human BPI, which
      is a bactericidal/permeability-increasing protein, and the other encodes Fc
      segment of human immunoglobulin G1 (Fcgamma1). Our results indicated that the
      target protein could be expressed and secreted into the serum of the gene
      transferred mice. After lethal endotoxin challenge, the levels of endotoxin and
      TNF-alpha in the gene-transferred mice were decreased. The survival rate of the
      BPI-Fcgamma1 gene-transferred mice was markedly increased. Our data suggest that
      AAV2-mediated chimeric BPI-Fcgamma1 gene delivery can potentially be used
      clinically for the protection and treatment of endotoxemia and endotoxic shock in
      high-risk individuals.

PMID- 16893505
TI  - Soluble mouse B7-H3 down-regulates dendritic cell stimulatory capacity to
      allogenic T cell proliferation and production of IL-2 and IFN-gamma.
AB  - B7-H3 is a recently identified member of the B7 gene family. Its ubiquitous
      expression in both lymphoid and nonlymphoid tissues suggests that it could play
      an important role in the maintenance of self-tolerance. However, the exact
      function of B7-H3 is still elusive. The purpose of current study is to
      demonstrate the possible function of soluble mouse B7-H3 for prevention of DC
      mediated T cell activation. For this purpose, we established a soluble mouse B7
      H3 fusion protein (mB7h3-hIg) eukaryotic expression vector (pmB7h3-hIg) with a C
      terminal human IgG1 Fc. A C57BL/6 (B6)-derived dendritic cell line (DC2.4 cells)
      was used for the establishment of stable transfectants for generation of soluble
      mB7h3-hIg. Ectopic mB7h3-hIg expression was confirmed by RT-PCR, Western blot and
      ELISA analyses. A 49.7 kD protein was detected by Western blot from DC2.4 cells
      transfected with pmB7h3-hIg. It was found that soluble mB7h3-hIg expression has
      no effect on cell cycling and apoptosis and the expression of CD80 and CD86 of
      the DC2.4 cells. However, ectopic soluble mB7h3-hIg expression was found to
      significantly affect the allo-stimulatory capability for DC2.4 cells. DC2.4 cells
      expressing soluble mB7h3-hIg showed a significant reduced allo-stimulatory
      capability as compared with the controls determined by MLC. Further studies
      revealed that soluble mB7h3-hIg could also inhibit IL-2 and IFN-gamma production
      of allogenic T cells. These results suggested a great potential of soluble B7-H3
      for treatment of graft rejection and autoimmume disease.

PMID- 16893506
TI  - Reducing alcohol-impaired driving crashes through the use of social marketing.
AB  - Over the past decade there has been little decrease in the number of alcohol
      related driving fatalities. During this time most interventions have been
      educational or legal. This paper presents the results of a field experiment that
      used social marketing to introduce a new ride program into three rural
      communities. Almost all people in the 21-34-year-old target know that they should
      not drive while impaired, and most agree it is not a good thing to do, but for
      many the opportunity to behave properly does not exist. The Road Crew program was
      developed using new product development techniques and implemented by developing
      broad coalitions within the communities. A key feature of the program included
      rides to, between, and home from bars in older luxury vehicles. Results showed a
      significant shift in riding/driving behavior, especially among 21-34-year olds, a
      projected 17% decline in alcohol-related crashes in the first year, no increase
      in drinking behavior, and large savings between the reactive cost of cleaning up
      after a crash and the proactive cost of avoiding a crash. Programs have become
      self-sustaining based on fares and tavern contributions, and have become part of
      the life style in the treatment communities.

PMID- 16893507
TI  - Intrapartum maternal glycemic control in women with insulin requiring diabetes: a
      randomized clinical trial of rotating fluids versus insulin drip.
AB  - OBJECTIVE: The purpose of this study was to determine whether continuous insulin
      infusion provides a greater degree of intrapartum maternal glycemic control than
      rotating between glucose and non-glucose containing intravenous fluids. STUDY
      DESIGN: Laboring patients with pregestational or gestational diabetes were
      recruited and randomized to an "insulin drip" or "rotating fluids" protocol. The
      primary outcome measure was mean maternal capillary blood glucose (CBG) levels
      (mg/dL). Power analysis indicated that 16 patients were needed in each arm to
      find a difference of 10 mg/dL. RESULTS: Fifteen patients were randomized to the
      rotating fluids protocol and 21 patients to an insulin drip. There was no
      difference in mean intrapartum maternal CBG levels (103.9 +/- 8.7 mg/dL and 103.2
      +/- 17.9 mg/dL in the rotating fluids and insulin drip group, respectively, P =
      .89). Neonatal outcomes were also similar between the 2 treatment groups.
      CONCLUSION: In patients with insulin requiring gestational diabetes, intrapartum
      glycemic control may be comparable with a standard adjusted insulin drip or a
      rotation of intravenous fluids between glucose and non-glucose containing fluids.

PMID- 16893509
TI  - Pitfalls of partial meta-analysis: single- versus multidose for the treatment of
      ectopic pregnancy.

PMID- 16893511
TI  - Neurodevelopmental outcome after laser therapy for twin-twin transfusion
      syndrome.

PMID- 16893510
TI  - Characterization of progesterone receptor isoform expression in fetal membranes.
AB  - OBJECTIVE: To quantify expression of progesterone receptor (PR) messenger RNA
      (mRNA) isoforms in fetal membranes, and to determine whether these levels change
      in culture. STUDY DESIGN: Placentas from women undergoing term cesarean delivery
      before labor were collected. Layers of amnion, chorion, and decidua were
      separated manually, enzymatically digested, and separated further with the use of
      a density gradient. RNA was extracted immediately and after culture for 48 hours,
      then analyzed by quantitative reverse transcription polymerase chain reaction for
      PR-A, PR-B, and beta-2 microglobulin mRNA expression. Separation of cell types
      was confirmed by immunohistochemistry. RESULTS: PR isoform expression was
      identified in fetal membranes, with levels highest in decidua and below the
      limits of detection in amnion. The ratio of PR-A/PR-B mRNA was not significantly
      different between cell layers. PR mRNA isoform levels did not differ
      significantly in fresh versus cultured cells. CONCLUSION: Quantitative reverse
      transcription polymerase chain reaction was used to quantitate expression of PR
      mRNA isoforms in cells of fetal membranes and to validate systems for further
      study of PR with respect to inflammation, infection, and preterm delivery.

PMID- 16893513
TI  - Effect of treatment of dentofacial deformity on masseter muscle thickness.
AB  - OBJECTIVE: The objective of the present study was to determine the modifications
      in masseter muscle thickness before and after interdisciplinary orthodontic,
      oromyofunctional and surgical treatment of class III dentofacial skeletal
      deformities (DFSD). DESIGN: Fifteen patients with class III DFSD participated in
      the study, denoted P1 group before the interdisciplinary treatment and P2 group
      (same patients) 6-8 months after surgery. Fifteen individuals with no DFSD were
      used as the control group. Bilateral ultrasonography (US) of the masseter muscle
      under resting and biting conditions was performed in the three groups. RESULTS:
      There was a significant difference (P<0.01) for all muscles tested between the
      control, P1 and P2 groups, with greater thickness for controls, intermediate
      thickness for P2, and the lowest thickness for P1 in all situations evaluated.
      CONCLUSION: We conclude that there was an increase in masseter muscle thickness
      after surgical correction of DFSD accompanied by interdisciplinary treatment,
      although the values were still lower than those observed in the control group.

PMID- 16893514
TI  - Construction of a BAC library and identification of Dmrt1 gene of the rice field
      eel, Monopterus albus.
AB  - A bacterial artificial chromosome (BAC) library was constructed using nuclear DNA
      from the rice field eel (Monopterus albus). The BAC library consists of a total
      of 33,000 clones with an average insert size of 115 kb. Based on the rice field
      eel haploid genome size of 600 Mb, the BAC library is estimated to contain
      approximately 6.3 genome equivalents and represents 99.8% of the genome of the
      rice field eel. This is first BAC library constructed from this species. To
      estimate the possibility of isolating a specific clone, high-density colony
      hybridization-based library screening was performed using Dmrt1 cDNA of the rice
      field eel as a probe. Both library screening and PCR identification results
      revealed three positive BAC clones which were overlapped, and formed a contig
      covering the Dmrt1 gene of 195 kb. By sequence comparisons with the Dmrt1 cDNA
      and sequencing of first four intron-exon junctions, Dmrt1 gene of the rice field
      eel was predicted to contain four introns and five exons. The sizes of first and
      second intron are 1.5 and 2.6 kb, respectively, and the sizes of last two introns
      were predicted to be about 20 kb. The Dmrt1 gene structure was conserved in
      evolution. These results also indicate that the BAC library is a useful resource
      for BAC contig construction and molecular isolation of functional genes.

PMID- 16893515
TI  - Cyclic stretch translocates the alpha2-subunit of the Na pump to plasma membrane
      in skeletal muscle cells in vitro.
AB  - The Na+-K+-ATPase and its regulation is important for maintaining membrane
      potential and transmembrane Na(+) gradient in all skeletal muscle cells and thus
      is essential for cell survival and function. In our previous study, cyclic
      stretch activated the Na pump in cultured skeletal muscle cells. Presently, we
      investigated whether this stimulation was the result of translocation of Na+-K+
      ATPase from endosomes to the plasma membrane, and also evaluated the role of
      phosphatidylinositol 3-kinase (PI 3-kinase), the activation of which initiated
      vesicular trafficking and targeting of proteins to specific cell compartments.
      Skeletal muscle cells were stretched at 25% elongation continuous for 24h using
      the Flexercell Strain Unit. The plasma membrane and endosome fractions were
      isolated and Western blotted to localize the Na+-K+-ATPase alpha1- and alpha2
      subunit protein. The results showed stretch increased Na+-K+-ATPase alpha1- and
      alpha2-subunit protein expression in plasma membrane fractions and decreased it
      in endosomes. The alpha2-subunit had a more dynamic response to mechanical
      stretch. PI 3-kinase inhibitors (LY294002) blocked the stretch-induced
      translocation of the Na+-K+-ATPase alpha2-subunit, while LY294002 had no effect
      on the transfer of alpha1-subunit. We concluded that cyclic stretch mainly
      stimulated the translocation of the alpha2-subunit of Na+-K+-ATPase from
      endosomes to the plasma membrane via a PI 3-kinase-dependent mechanism in
      cultured skeletal muscle cells in vitro, which in turn increased the activity of
      the Na pump.

PMID- 16893517
TI  - Analysis of hybridization on the molecular barcode GeneChip microarray.
AB  - Microarrays have been developed for analysis of transcriptional profiles in many
      organisms. For experimental simplicity and systems for which microarrays do not
      exist, it would be desirable to use a standard microarray platform for the
      analysis of multiple systems. The molecular barcode (MB) Affymetrix GeneChip
      could serve as such a platform. The reproducibility and quantitative capacity of
      the MB GeneChip were examined. Using mixed PCR templates of defined template
      quantity, the individual concentration responses of 384 array features were
      measured and shown to be highly reproducible. Moreover, the binding behaviors of
      the mismatched array features mirror those of the matched features, at reduced
      intensity. Additional analysis defined the importance of particular sequence
      motifs in the prediction of high-affinity and low-affinity target hybridization.
      The data support the future application of MB GeneChips for quantitative
      applications. It is proposed that at least seven orders-of-magnitude in accurate
      concentration sensitivity could be achieved.

PMID- 16893516
TI  - Predominance of interaction among wild-type alleles of CYP11B2 in Himalayan
      natives associates with high-altitude adaptation.
AB  - Sojourners visiting high-altitude (HA) (>2500 m) are susceptible to HA disorders;
      on the contrary, HA natives are well adapted to the extreme hypoxic environment.
      High aldosterone levels are believed to be involved in HA disorders, we,
      therefore, envisaged role of CYP11B2 gene variants in HA adaptation and therefore
      investigated the -344T/C, intron-2 conversion (Iw/Ic), K173R, and A5160C
      polymorphisms. In addition, polymorphisms in AGT, AT1R, ATP1A1, ADRB2, and GSTP1
      genes were also investigated. The study comprised of 662 subjects, comprising of
      426 Himalayan highlanders (HLs) and 236 lowlanders (LLs). The -344T/C and K173R
      polymorphisms were found to be in complete linkage disequilibrium. The wild-type
      allele -344T and combination of wild-type homozygous genotypes between -344T/C,
      Iw/Ic, and A5160C polymorphisms, containing all the six wild-type alleles were
      over-represented in the HLs (p < 0.0001, and p = 0.008, respectively). The wild
      type haplotypes -344T-Iw, -344T-5160A, and -344T-Iw-5160A also showed over
      representation in the HLs (p < 0.0001). Furthermore, greater the number of wild
      type alleles, lower was the ARR (p < 0.05). The genotype distribution in
      remaining genes did not differ. To conclude, the over-representation of wild-type
      -344T allele, genotype combinations and haplotypes of CYP11B2, and their
      correlation with lower aldosterone levels associate with HA adaptation in the
      HLs. Such an allelic presentation in sojourners may help them cope with adverse
      HA environment.

PMID- 16893518
TI  - Identification of a novel exon encoding the amino-terminus of the predominant
      caspase-5 variants.
AB  - Caspase-5 is a caspase-1-like protease with pro-apoptotic and pro-inflammatory
      activities. Here we have identified a novel exon at the 5'-end of the human
      caspase-5 gene. This novel exon was present in six alternatively spliced caspase
      5 mRNA variants expressed in human peripheral blood mononuclear cells (PBMC) and
      encoded the previously unknown amino-terminus of caspase-5. The genomic region
      upstream of this exon contained sequence elements homologous to those of the
      caspase-11 promoter in the mouse, and transcription of caspase-5 was upregulated
      by lipopolysaccharide (LPS) in a caspase-11-like manner in human PBMC in vivo.
      Taken together, our findings call for a revision of the structure of caspase-5 at
      the genomic level as well as at the mRNA and protein levels.

PMID- 16893520
TI  - Aspirin upregulates expression of urokinase type plasminogen activator receptor
      (uPAR) gene in human colon cancer cells through AP1.
AB  - In this study, the effects of acetylsalicylic acid (aspirin) on the expression of
      uPAR and the mechanism by which it regulates expression of uPAR was examined in
      two different colon cancer cell lines HCT116 and GEO, respectively. The study
      shows that under physiological concentration, aspirin upregulates steady-state
      level expression of uPAR mRNA as well as expression of uPAR protein. Using a
      transient transfection assay, a region corresponding to -1 to -398 region of uPAR
      promoter has been identified which shows maximum responsiveness to aspirin
      treatment and found that this region is sufficient for the aspirin-induced up
      regulation of uPAR. A stable integration of a single copy of this region coupled
      to luciferase reporter gene into the HCT116 genome also behaved similarly. Using
      gel mobility shift assays, it is found that the distal AP1 region between -171
      and -186 is responsible for the aspirin-induced up-regulation of uPAR. Mutation
      of this region reduced up-regulation. Supershift assays identify that the bound
      proteins at this region are c-Jun and Fra-1. Real-time PCR analysis showed more
      than 4-fold increase in the binding of c-Jun and a 1.6-fold increase in the
      binding of Fra-1 in this region and this up-regulation corresponds to an
      increased binding of acetylated histone H4 in this region. Since an increase in
      the expression of uPAR corresponds to an increase in the migration of the cell, a
      migration assay was performed and result showed a 3-fold increased migration of
      HCT116 cells through the vitronectin-coated layer. Thus, an AP1 mediated pathway
      for aspirin induced up-regulation of uPAR has been identified.

PMID- 16893519
TI  - Imaging of multiple mRNA targets using quantum dot based in situ hybridization
      and spectral deconvolution in clinical biopsies.
AB  - Gene expression mapping using microarray analysis has identified useful gene
      signatures for predicting outcome. However, little of this has been translated
      into clinically effective diagnostic tools as microarrays require high quality
      fresh-frozen tissue samples. We describe a methodology of multiplexed in situ
      hybridization (ISH) using a novel combination of quantum dot (QD)-labeled
      oligonucleotide probes and spectral imaging analysis in routinely processed,
      formalin-fixed paraffin embedded human biopsies. The conditions for QD-ISH were
      optimized using a poly d(T) oligonucleotide in decalcified bone marrow samples.
      Single and multiplex QD-ISH was performed in samples with acute leukemia and
      follicular lymphoma using oligonucleotide probes for myeloperoxidase, bcl-2,
      survivin, and XIAP. Spectral imaging was used for post hybridization tissue
      analysis, enabling separation of spatially colocalized signals. The method allows
      quantitative characterization of multiple gene expression using non-bleaching
      fluorochromes. This is expected to facilitate multiplex in situ transcript
      detection in routinely processed human clinical tissue.

PMID- 16893521
TI  - Surface exposed epitopes and structural heterogeneity of in vivo formed
      transthyretin amyloid fibrils.
AB  - We have investigated the structure of in vivo formed transthyretin (TTR) amyloid
      deposits by using antisera raised against short linear sequences of the TTR
      molecule. In immunohistochemistry, antisera anti-TTR41-50 and anti-TTR115-124-a
      reacted specifically with both wildtype ATTR and ATTR V30M material, whereas only
      anti-TTR41-50 recognized ATTR Y114C material. Similar results were obtained by
      ELISA analysis of ATTR V30M and ATTR Y114C vitreous amyloid, where the anti
      TTR115-124-a antiserum failed to react with ATTR Y114C material. Moreover,
      neither of the antisera recognized natively structured TTR present in pancreatic
      alpha cells. Our results strongly indicate that the TTR molecule undergoes
      structural changes during fibrillogenesis in vivo. The finding of a structural
      difference between wildtype ATTR and ATTR V30M material on one hand and ATTR
      Y114C material on the other suggests that the fibril formation pathway of these
      ATTR variants may differ in vivo.

PMID- 16893522
TI  - N-terminal peptides from unprocessed prion proteins enter cells by
      macropinocytosis.
AB  - A peptide derived from the N-terminus of the unprocessed bovine prion protein
      (bPrPp), incorporating the hydrophobic signal sequence (residues 1-24) and a
      basic domain (KKRPKP, residues 25-30), internalizes into mammalian cells, even
      when coupled to a sizeable cargo, and therefore functions as a cell-penetrating
      peptide (CPP). Confocal microscopy and co-localization studies indicate that the
      internalization of bPrPp is mainly through macropinocytosis, a fluid-phase
      endocytosis process, initiated by binding to cell-surface proteoglycans. Electron
      microscopy studies show internalized bPrPp-DNA-gold complexes residing in
      endosomal vesicles. bPrPp induces expression of a complexed luciferase-encoding
      DNA plasmid, demonstrating the peptide's ability to transport the cargo across
      the endosomal membrane and into the cytosol and nucleus. The novel CPP activity
      of the unprocessed N-terminal domain of PrP could be important for the
      retrotranslocation of partly processed PrP and for PrP trafficking inside or
      between cells, with implications for the infectivity associated with prion
      diseases.

PMID- 16893523
TI  - A randomized, double-blind study of continuation treatment for attention
      deficit/hyperactivity disorder after 1 year.
AB  - BACKGROUND: The efficacy of atomoxetine in maintaining symptom response following
      1 year of treatment was assessed in children and adolescents (n = 163) with DSM
      IV defined attention-deficit/hyperactivity disorder (ADHD). METHODS: Subjects had
      previously responded to atomoxetine acutely and had completed 1 year of double
      blind atomoxetine treatment. They were then randomly assigned in double-blind
      fashion to continued atomoxetine or placebo substitution for 6 months. RESULTS:
      Atomoxetine was superior to placebo in preventing relapse (Wilcoxon test, p =
      .008) and in maintaining symptom response (ADHD Rating Scale IV score, p < .001).
      Among subjects assigned to discontinuation, the magnitude of symptom return was
      generally to a level of severity less than that observed at study entry.
      CONCLUSIONS: Following 1 year of treatment with atomoxetine, continued treatment
      over the ensuing 6 months was associated with superior outcomes compared with
      placebo substitution. However, there was considerable variability between
      individuals in the magnitude of symptom return after drug discontinuation,
      suggesting that some subjects treated with atomoxetine for a year with good
      results may consolidate gains made during drug treatment and could benefit from a
      medication-free trial to assess the need for ongoing drug treatment.

PMID- 16893524
TI  - Gamma band oscillations reveal neural network cortical coherence dysfunction in
      schizophrenia patients.
AB  - BACKGROUND: Gamma band activity has been associated with many sensory and
      cognitive functions, and is important for cortico-cortical transmission and the
      integration of information across neural networks. The aims of the present study
      were to determine if schizophrenia patients have deficits in the generation and
      maintenance of coherent, synchronized oscillations in response to steady-state
      stimulation, and to examine the clinical and cognitive correlates of the
      electroencephalography (EEG) oscillatory dynamics. METHODS: Schizophrenia
      patients (n = 100) and nonpsychiatric subjects (n = 80) underwent auditory steady
      state event-related potential testing. Click trains varying in rate of
      stimulation (20, 30, and 40 Hz) were presented; EEG-evoked power and intertrial
      phase synchronization were obtained in response to each stimulation frequency.
      Subjects also underwent clinical and neurocognitive assessments. RESULTS:
      Patients had reductions in both evoked power and phase synchronization in
      response to 30- and 40-Hz stimulation but normal responsivity to 20-Hz
      stimulation. Maximal deficits were detected in response to 40-Hz stimulation. A
      modest association of reduced working memory performance and 40-Hz intertrial
      phase synchronization was present in schizophrenia patients (r = .32, p <.01).
      CONCLUSIONS: Schizophrenia patients have frequency-specific deficits in the
      generation and maintenance of coherent gamma-range oscillations, reflecting a
      fundamental degradation of basic integrated neural network activity.

PMID- 16893525
TI  - Systemic and central amygdala injections of the mGluR(2/3) agonist LY379268
      attenuate the expression of incubation of cocaine craving.
AB  - BACKGROUND: We and others reported time-dependent increases in cue-induced
      cocaine seeking after withdrawal, suggesting that craving incubates over time.
      Recently, we found that central amygdala extracellular signal-regulated kinases
      (ERK) and glutamate are involved in this incubation. Here, we further explored
      the role of central amygdala glutamate in the incubation of cocaine craving by
      determining the effect of systemic or central amygdala injections of the mGluR2/3
      agonist LY379268 (which decreases glutamate release) on cue-induced cocaine
      seeking during early and late withdrawal. METHODS: Rats were trained to self
      administer cocaine for 10 days (6 hours/day); infusions were paired with a tone
      light cue. Cocaine seeking and craving after systemic or central amygdala
      injections of LY379268 were then assessed in extinction tests in the presence of
      the cocaine-associated cues during early (day 3) or late (day 21) withdrawal.
      RESULTS: Systemic (1.5 or 3 mg/kg) or central amygdala (.5 or 1.0 microg/side)
      injections of LY379268 attenuated enhanced extinction responding on day 21 but
      had no effect on lower extinction responding on day 3. CONCLUSIONS: Results
      confirm our previous findings on the role of central amygdala glutamate in the
      incubation of cocaine craving and together with previous reports suggest that
      mGluR(2/3) agonists should be considered in the treatment of drug relapse.

PMID- 16893527
TI  - Decreased plasma brain derived neurotrophic factor levels in unmedicated bipolar
      patients during manic episode.
AB  - BACKGROUND: Bipolar disorder (BD) has been increasingly associated with
      abnormalities in neuroplasticity and cellular resilience. Brain Derived
      Neurotrophic Factor (BDNF) gene has been considered an important candidate marker
      for the development of bipolar disorder and this neurotrophin seems involved in
      intracellular pathways modulated by mood stabilizers. Also, previous studies
      demonstrated a role for BDNF in the pathophysiology and clinical presentation of
      mood disorders. METHODS: We investigated whether BDNF levels are altered during
      mania. Sixty subjects (14 M and 46 F) were selected and included in the study.
      Thirty patients meeting SCID-I criteria for manic episode were age and gender
      matched with thirty healthy controls. Young Mania Rating Scale (YMRS) evaluated
      the severity of manic episode and its possible association with the neurotrophin
      levels. RESULTS: Mean BDNF levels were significantly decreased in drug free/naive
      (224.8 +/- 76.5 pg/ml) compared to healthy controls (318.5 +/- 114.2), p < .001].
      Severity of the manic episode presented a significant negatively correlation to
      plasma BDNF levels (r= .78; p < .001; Pearson test). CONCLUSIONS: Overall, these
      results suggest that the decreased plasma BDNF levels may be directly associated
      with the pathophysiology and severity of manic symptoms in BD. Further studies
      are necessary to clarify the role of BDNF as a putative biological marker in BD.

PMID- 16893526
TI  - Effect of tryptophan depletion on smokers and nonsmokers with and without history
      of major depression.
AB  - BACKGROUND: Serotonergic dysregulation is posited to contribute to comorbidity
      between nicotine dependence and depression. We tested whether acute tryptophan
      depletion (ATD) triggers depressive symptoms in euthymic, unmedicated smokers and
      nonsmokers with and without history of major depressive disorder (MDD). METHODS:
      Acute tryptophan depletion and taste-matched placebo challenges were administered
      double-blind in counter-balanced order. Participants were four groups of
      volunteers hypothesized to be of increasing affective vulnerability as follows:
      nonsmokers lacking recurrent personal and familial history of MDD (n = 20),
      smokers lacking recurrent personal and familial history of MDD (n = 21),
      nonsmokers with history of recurrent personal and familial MDD (n = 16), and
      smokers with recurrent personal and familial history of MDD (n = 16). Depression,
      dysphoric mood, and plasma amino acids were measured at baseline and around the
      time of peak depletion. RESULTS: Depressive symptom response to ATD was
      heightened significantly by history of MDD (p < .001) and marginally by smoking
      (p = .09). Smoking seemed to magnify the ATD response of those with a history of
      MDD (effect size = .63) but had no effect on those without MDD history (effect
      size = .06). CONCLUSIONS: Depressive symptom response to serotonergic challenge
      is exaggerated in unmedicated, euthymic adults with recurrent personal and
      familial vulnerability to MDD, perhaps especially if they also smoke.

PMID- 16893528
TI  - Juvenile administration of methylphenidate attenuates adult hippocampal
      neurogenesis.
AB  - BACKGROUND: The neural consequences of early-life exposure to methylphenidate
      (MPH; Ritalin) are of great interest given the widespread, and sometimes
      inappropriate, use in children. Here we examine the impact of juvenile MPH
      exposure on adult hippocampal neurogenesis. METHODS: Rats received MPH (2.0
      mg/kg, intraperitoneal, twice daily) or saline (SAL) during preadolescence
      (postnatal days 20-35). Hippocampal cell proliferation (Experiment 1),
      neurogenesis (Experiment 2), and stress-induced changes in cell proliferation
      (Experiment 3) were assessed at several developmental stages including adulthood.
      RESULTS: Juvenile exposure to MPH did not alter proliferation at any
      developmental time point relative to control rats; however, exposure to MPH
      significantly decreased the long-term survival of newborn cells in adult rats,
      particularly in the temporal hippocampus. Although MPH-treated rats had higher
      levels of corticosterone after restraint stress, they did not show the expected
      greater decrease in hippocampal cell proliferation relative to control animals.
      CONCLUSIONS: Early-life exposure to MPH inhibits the survival of adult-generated
      neurons in the temporal hippocampus and may reduce progenitor sensitivity to
      corticosterone-induced decreases in proliferation. These findings suggest that
      decreased adult neurogenesis is an enduring consequence of early-life exposure to
      MPH and are discussed for their relevance to humans.

PMID- 16893529
TI  - Association of fatty acid desaturase genes with attention-deficit/hyperactivity
      disorder.
AB  - BACKGROUND: Fatty acids, in particular omega-3 fatty acids, have been found to
      affect behavior and cognition both directly and indirectly. Evidence to suggest a
      link with attention-deficit/hyperactivity disorder (ADHD) derives from three key
      areas: 1) animal dietary restriction studies observed increased locomotive
      hyperactivity and reduced cognitive ability in offspring; 2) animal dietary
      studies indicate alterations in the dopamine pathway; and 3) human studies report
      reduced plasma omega-3 fatty acids in ADHD subjects. METHODS: We investigated
      three genes that encode essential enzymes (desaturases) for the metabolism of
      fatty acids by scanning for genetic association between 45 single nucleotide
      polymorphisms (SNPs) and ADHD. RESULTS: Our findings suggest a significant
      association of ADHD with SNP rs498793 (case-control p = .004, odds ratio [OR]
      1.6, 95% confidence interval [CI] 1.15-2.23; transmission disequilibrium test
      [TDT] p = .014, OR 1.69) in the fatty acid desaturase 2 (FADS2) gene. As alcohol
      is known to decrease the activities of these desaturase enzymes, we also tested
      for interactions between ADHD subjects' genotypes and maternal use of alcohol
      during pregnancy. Two SNPs in the fatty acid desaturase 1 (FADS1) gene were
      nominally associated with ADHD only in the prenatal alcohol-exposed group of
      children; formal test for interaction was not significant. CONCLUSIONS: These
      preliminary findings are suggestive of an association between FADS2 and ADHD.

PMID- 16893531
TI  - The effects of norepinephrine transporter inactivation on locomotor activity in
      mice.
AB  - BACKGROUND: Acute administration of different classes of antidepressants can
      enhance or reduce spontaneous locomotor activity in a novel environment, but the
      effects of chronic antidepressant treatment on spontaneous locomotor activity in
      novel and familiar environments are less well characterized. Because
      norepinephrine is an important regulator of spontaneous locomotor activity, we
      speculated that norepinephrine transporter blockade contributes to the effects of
      some antidepressants on spontaneous locomotor activity. METHODS: Antidepressant
      drugs (reboxetine, desipramine, imipramine, venlafaxine, bupropion) were
      administered acutely (intraperitoneal) or chronically (via osmotic minipump) to
      control and norepinephrine transporter knockout mice, and spontaneous locomotor
      activity in novel or familiar environments was recorded. RESULTS: Acute treatment
      with most norepinephrine transporter-blocking antidepressants decreased
      spontaneous locomotor activity in a novel environment, whereas chronic treatment
      decreased spontaneous locomotor activity in both novel and familiar environments.
      The exception was bupropion, a dual norepinephrine transporter/dopamine
      transporter blocker, which tended to increase spontaneous locomotor activity.
      Coadministration of reboxetine and the dopamine transporter blocker GBR 12909
      also increased spontaneous locomotor activity. Norepinephrine transporter
      knockout mice had low basal spontaneous locomotor activity, which was increased
      by bupropion, whereas reboxetine had no effect in norepinephrine transporter
      knockout mice. CONCLUSIONS: Acute or chronic inactivation of the norepinephrine
      transporter decreases spontaneous locomotor activity in novel and familiar
      environments unless coupled with dopamine transporter blockade.

PMID- 16893530
TI  - Nur77 gene knockout alters dopamine neuron biochemical activity and dopamine
      turnover.
AB  - BACKGROUND: Transcription factors of the Nur family (Nurr1, Nur77, and Nor-1) are
      orphan nuclear receptors closely associated with dopamine neurotransmission in
      the central nervous system. Nur77 expression is strongly modulated by
      antipsychotic and ant-parkinsonian drugs in dopaminoceptive brain areas. However,
      the role of Nur77 in dopamine neuron activity and turnover remains elusive.
      METHODS: We compared various behavioral and biochemical parameters between Nur77
      knockout -/- and wild-type +/+ mice in basal and haloperidol-challenged
      conditions. RESULTS: We report here that Nur77-deficient mice display enhanced
      spontaneous locomotor activity, greater sensitivity to a small dose of the
      dopamine D2 receptor agonist quinpirole acting mainly at autoreceptor sites, and
      higher levels of the dopamine metabolite DOPAC relative to wild-type mice.
      Dopamine turnover disturbances are also found after acute challenge with
      haloperidol, a dopamine D2 receptor antagonist. These alterations are associated
      with increased tyrosine hydroxylase expression and activity, and reduced catechol
      O-methyltransferase expression. CONCLUSION: Taken together, these results are
      consistent with the involvement of Nur77 in dopamine neuron biochemical activity
      and dopamine turnover.

PMID- 16893532
TI  - Novel, replicated associations between dopamine D3 receptor gene polymorphisms
      and schizophrenia in two independent samples.
AB  - BACKGROUND: Meta-analyses have suggested an association between schizophrenia
      (SZ) and a coding polymorphism (rs6280/Ser9Gly) at the dopamine D3 receptor gene
      (DRD3), but results have been inconsistent. Because most studies have evaluated
      only rs6280, the inconsistencies might reflect associations with other variants.
      METHODS: We analyzed polymorphisms spanning 109kb in two independent samples
      (United States: 13 single nucleotide polymorphisms (SNPs), 331 cases, 151 trios,
      274 control subjects; India: 11 SNPs, 141 trios). RESULTS: In the U.S. samples,
      significant associations were detected with eight SNPs, including rs6280 (p =
      .001, odds ratio: 1.5). Consistent associations in the case-control and family
      based analyses were detected with a common haplotype spanning intron 1 to the 3'
      region of the gene (rs324029-rs7625282-rs324030-rs2134655-rs10934254; case
      control, p = .002; transmission disequilibrium test [TDT], p = .0009; global p
      values = .002 and .007, respectively). In the Indian sample, one SNP was
      associated (rs10934254, p = .03). Moreover, over-transmission of the same common
      haplotype as the U.S. sample was observed in this cohort (TDT, p = .005; global
      test, p = .009). Ser9Gly (rs6280) was associated with SZ against this haplotype
      background but not other haplotypes. CONCLUSIONS: These data suggest previous
      inconsistencies might have resulted from associations with other DRD3 variants. A
      liability locus might be in linkage disequilibrium (LD) with or carried against,
      an associated haplotype 3' to rs6280. Comprehensive SNP evaluation in larger
      samples is needed.

PMID- 16893533
TI  - Diffusion tensor imaging in schizophrenia.
AB  - BACKGROUND: Alignment of white matter axons as inferred from diffusion tensor
      imaging has indicated changes in schizophrenia in frontal and frontotemporal
      white matter. METHODS: Diffusion tensor anisotropy and anatomical magnetic
      resonance images were acquired in 64 patients with schizophrenia and 55 normal
      volunteers. Anatomical images were acquired with a magnetization prepared rapid
      gradient echo sequence, and diffusion tensor images used a pulsed gradient spin
      echo acquisition. Images were aligned and warped to a standard brain, and
      anisotropy in normal volunteers and patients was compared using significance
      probability mapping. RESULTS: Patients showed widespread areas of reduced
      anisotropy, including the frontal white matter, the corpus callosum, and the
      frontal longitudinal fasciculus. CONCLUSIONS: These findings, which are
      consistent with earlier reports of frontal decreases in anisotropy, demonstrate
      that the effects are most prominent in frontal and callosal areas and are
      particularly widespread in frontal white matter regions.

PMID- 16893534
TI  - Lexical stress encoding in single word production estimated by event-related
      brain potentials.
AB  - An event-related brain potentials (ERPs) experiment was carried out to
      investigate the time course of lexical stress encoding in language production.
      Native speakers of Dutch viewed a series of pictures corresponding to bisyllabic
      names which were either stressed on the first or on the second syllable and made
      go/no-go decisions on the lexical stress location of those picture names.
      Behavioral results replicated a pattern that was observed earlier, i.e. faster
      button-press latencies to initial as compared to final stress targets. The
      electrophysiological results indicated that participants could make a lexical
      stress decision significantly earlier when picture names had initial than when
      they had final stress. Moreover, the present data suggest the time course of
      lexical stress encoding during single word form formation in language production.
      When word length is corrected for, the temporal interval for lexical stress
      encoding specified by the current ERP results falls into the time window
      previously identified for phonological encoding in language production.

PMID- 16893535
TI  - Growth hormone, VEGF and FGF: involvement in rheumatoid arthritis.
AB  - Adult rheumatoid arthritis (RA), a systemic autoimmune disorder of unknown
      etiology, is characterized by dysfunctional cellular and humoral immunity,
      enhanced migration and attachment of peripheral macrophages and pro-inflammatory
      leukocytes to the synovium and articular cartilage of diarthrodial joints. The
      progressive destruction of cartilage and bone in RA is a result of elevated pro
      inflammatory cytokine gene expression, synovial neovascularization, proteinase
      mediated dissolution of articular cartilage matrix and osteoclast-mediated
      subchondral bone resorption. Juvenile chronic arthritis (JCA) is disease with
      manifestations similar to adult RA that occurs in childhood. JCA usually causes
      precocious joint destruction and often also presents with evidence of growth
      plate anomalies and reduced stature. Three proteins play an integral role in both
      adult RA and JCA. These are somatotropin (also called pituitary growth hormone
      (GH)), vascular endothelial growth factor (VEGF) and fibroblast growth factor
      (FGF). GH is responsible for regulating long bone growth and skeletal maturation
      through its capacity to stimulate insulin-like growth factor-I (IGF-1) synthesis
      by hepatocytes. Mechanisms responsible for growth plate disturbances and short
      stature in children with JCA include deficient GH production, GH-insensitivity
      resulting from defects in the GH receptor, suppressed IGF-1 synthesis or
      neutralization of IGF-1 action by IGF-1 binding proteins (IGFBPs). In addition,
      GH has also been implicated in perpetuating inflammation and pain in adult RA.
      VEGF has been shown to be the critical angiogenesis factor responsible for
      vascular proliferation and blood vessel invasion of the synovial lining membrane
      in RA. Acidic FGF (FGF-1) and basic FGF (FGF-2) have also been implicated in
      aberrant synoviocyte proliferation (i.e. synovial hyperplasia) and apoptosis
      resistance in adult RA.

PMID- 16893536
TI  - Testing the shared resource assumption in theories of text processing.
AB  - Eight experiments evaluated a core assumption of several theories of text
      processing, the shared resource assumption, which states that component text
      processes share limited processing resources. Short texts each contained two
      critical sentences that together warranted a causal inference. The syntactic
      structure of the second sentence was either more or less difficult to parse.
      Results from a lexical decision task suggested that readers formed the causal
      inferences when the syntactic structure was less difficult to parse but that
      inferencing was constrained when syntactic structure was more difficult. Follow
      up experiments suggested that this interference was not due to inferior output of
      the syntactic parser nor to the increased demands of difficult syntax interfering
      with maintenance of information needed to form the inference. The results suggest
      insufficient resources were available for the operation of inference processes
      due to the increased demands of syntactic parsing, consistent with the shared
      resource assumption.

PMID- 16893537
TI  - An algorithm for the recovery of fetal heart rate series from CTG data.
AB  - Cardiotocography (simultaneous recording of fetal heart rate (FHR) and uterine
      contractions) is one of the most used diagnostic techniques to evaluate fetal
      well-being and to investigate the functional state of the fetal autonomic nervous
      system. Recently, great interest has been paid to the variability of the FHR, and
      its frequency analysis, as a base for a more objective analysis of the
      cardiotocographic (CTG) tracings. FHR signals are unevenly sampled series. To
      obtain evenly sampled series, cardiotocographs often use zero-order
      interpolation. Such process is simple and fast but results unsuitable for
      frequency analyses because it introduces alterations in the FHR power spectrum.
      An algorithm for the recovery of the true FHR series out of the zero-order
      interpolated CTG data was developed and evaluated.

PMID- 16893538
TI  - Comparison of human whole blood, plasma, and serum matrices for the determination
      of perfluorooctanesulfonate (PFOS), perfluorooctanoate (PFOA), and other
      fluorochemicals.
AB  - Interest in human exposure to perfluorinated acids, including
      perfluorobutanesulfonate (PFBS), perfluorohexanesulfonate (PFHS),
      perfluorooctanesulfonate (PFOS), and perfluorooctanoate (PFOA) has led to their
      measurement in whole blood, plasma and serum. Comparison of measurements in these
      different blood-based matrices, however, has not been rigorously investigated to
      allow for across-matrix comparisons. This research evaluated concentrations of
      PFBS, PFHS, PFOS, and PFOA in whole blood collected in heparin (lithium) and
      ethylenediamine tetraacetic acid (EDTA), plasma samples collected in heparin and
      EDTA, and serum (from whole blood allowed to clot). Blood samples were collected
      from 18 voluntary participants employed at 3M Company. Solid phase extraction
      methods were used for all analytical sample preparations, and analyses were
      completed using high-pressure liquid chromatography/tandem mass spectrometry
      methods. Serum concentrations ranged from: limit of quantitation (LOQ, 5 ng/mL)
      to 25 ng/mL for PFBS; LOQ (5 ng/mL) to 75 ng/mL for PFHS; LOQ (5 ng/mL) to 880
      ng/mL for PFOS; and LOQ (5 or 10 ng/mL) to 7320 ng/mL for PFOA. Values less than
      the LOQ were not included in the statistical analyses of the mean of the ratios
      of individual values for the matrices. PFBS was not quantifiable in most samples.
      Serum to plasma ratios for PFHS, PFOS, and PFOA were 1:1 and this ratio was
      independent of the level of concentrations measured. Serum or plasma to whole
      blood ratios, regardless of the anticoagulant used, approximated 2:1. The
      difference between plasma and serum and whole blood corresponded to volume
      displacement by red blood cells, suggesting that the fluorochemicals are not
      found intracellularly or attached to the red blood cells.

PMID- 16893539
TI  - Inhibition of cyclooxygenase (COX)-2 affects endothelial progenitor cell
      proliferation.
AB  - Growing evidence indicates that inducible cyclooxygenase-2 (COX-2) is involved in
      the pathogenesis of inflammatory disorders and various types of cancer.
      Endothelial progenitor cells recruited from the bone marrow have been shown to be
      involved in the formation of new vessels in malignancies and discussed for being
      a key point in tumour progression and metastasis. However, until now, nothing is
      known about an interaction between COX and endothelial progenitor cells (EPC).
      Expression of COX-1 and COX-2 was detected by semiquantitative RT-PCR and Western
      blot. Proliferation kinetics, cell cycle distribution and rate of apoptosis were
      analysed by MTT test and FACS analysis. Further analyses revealed an implication
      of Akt phosphorylation and caspase-3 activation. Both COX-1 and COX-2 expression
      can be found in bone-marrow-derived endothelial progenitor cells in vitro. COX-2
      inhibition leads to a significant reduction in proliferation of endothelial
      progenitor cells by an increase in apoptosis and cell cycle arrest. COX-2
      inhibition leads further to an increased cleavage of caspase-3 protein and
      inversely to inhibition of Akt activation. Highly proliferating endothelial
      progenitor cells can be targeted by selective COX-2 inhibition in vitro. These
      results indicate that upcoming therapy strategies in cancer patients targeting
      COX-2 may be effective in inhibiting tumour vasculogenesis as well as angiogenic
      processes.

PMID- 16893540
TI  - Retinal ganglion cell survival in development: mechanisms of retinal growth
      hormone action.
AB  - Several variants of growth hormone (GH) are found in the retina and vitreous of
      the chick embryo, where they appear to act as cell survival factors, having
      neuroprotective effects on retinal ganglion cells (RGCs). Here, we investigate
      the molecular mechanisms of the anti-apoptotic effect of GH in cultured RGCs. GH
      treatment increased Akt phosphorylation in these cells, which is an anti
      apoptotic event. Whereas unphosphorylated Akt was detected in both nucleus and
      cytoplasm of RGCs by immunocytochemistry, the phosphorylated form of Akt (Akt
      phos) was located primarily in the cytoplasm of both normal and apoptotic cells,
      although levels were markedly lower in the latter. It was found that GH treatment
      of RGCs reduced Akt levels, while concomitantly raising Akt-phos levels,
      consistent with a role for Akt signaling pathways in GH neuroprotective action.
      This was substantiated using Wortmannin, which, like GH antiserum, inhibited Akt
      phosphorylation and initiated apoptosis. The addition of Wortmannin to RGC
      cultures simultaneously with GH significantly reduced the anti-apoptotic effect
      of GH. The induction of apoptosis by GH antiserum was clearly accompanied by an
      increase in caspase-3 activation and PARP-1 cleavage, both of which were
      significantly reduced in the presence of the broad spectrum caspase inhibitor, Q
      VD-OPh, which itself had a dramatic neuroprotective effect on cultured RGCs.
      Calpain activation appeared to be a major caspase-independent pathway to PARP-1
      cleavage and apoptosis in these cells. Calpain inhibitor III (MDL 28170) was able
      to reduce PARP-1 cleavage and abrogate the apoptogenic effect of GH antiserum.
      The results support the view that caspase and calpain inhibitors are major
      neuroprotective agents for RGCs, and that pathways that activate both caspases
      and calpains are important for the anti-apoptotic actions of GH in these cells.

PMID- 16893541
TI  - The role of cathepsins in ocular physiology and pathology.
AB  - Cathepsins are proteases that were originally identified in the lysosome, where
      they participate in house keeping tasks such as degradation of phagocytosed
      photoreceptors. More recently, cathepsins have been detected outside of the
      lysosome, and associated with numerous diseases (keratoconus, retinal detachment,
      age related macular degeneration, and glaucoma). The most likely mechanism by
      which cathepsins contribute to ocular pathologies is via degradation of the
      extracellular matrix, and/or regulation of angiogenesis.

PMID- 16893542
TI  - Identification of mobile cholesterol compounds in experimental gliomas by (1)H
      MRS in vivo: effects of ganciclovir-induced apoptosis on lipids.
AB  - This letter presents a novel identification and analysis of mobile cholesterol
      compounds in an experimental glioma model by (1)H MRS in vivo. The cholesterol
      compounds turned out to comprise as much as 17 mol% of MRS visible total lipids.
      The results also imply partly associated accumulation of (1)H MRS detectable
      cholesterol compounds and unsaturated lipids during gene therapy-induced
      apoptosis, and indicate that the contribution of cholesterol compounds cannot be
      bypassed in spectral lipid analysis. The introduced (1)H MRS approach facilitates
      a non-invasive follow-up of mobile cholesterol compounds, paving way for studies
      of tumour cholesterol metabolism in vivo.

PMID- 16893543
TI  - Use of inferior epigastric artery embolization to arrest bleeding at operative
      laparoscopy.
AB  - OBJECTIVE: To describe an innovative approach of embolization of the inferior
      epigastric artery after vascular trauma due to lateral trocar insertion at
      operative laparoscopy. DESIGN: Case report. SETTING: Operating theater and
      interventional radiology suite of a university hospital. PATIENT(S): A 26-year
      old woman with polycystic ovaries refractory to clomiphene citrate undergoing
      laparoscopic ovarian drilling. INTERVENTION(S): Percutaneous selective left
      external iliac and left inferior epigastric angiography followed by embolization
      with platinum microcoils and polyvinyl alcohol. MAIN OUTCOME MEASURE(S):
      Satisfactory hemostasis following traumatic injury to the inferior epigastric
      artery. RESULT(S): Hemostasis was achieved using a novel interventive radiologic
      approach of embolization of the inferior epigastric artery after conventional
      surgical techniques had failed. CONCLUSION(S): Arterial embolization is a novel
      additional measure in the armamentarium of the laparoscopic surgeon faced with
      intractable bleeding from the inferior epigastric vessels.

PMID- 16893544
TI  - Mature cystic teratoma of the fallopian tube.
AB  - A mature cystic teratoma within the fallopian tube was discovered at the time of
      laparoscopy for dysmenorrhea, dyspareunia, and infertility. A linear
      salpingostomy was performed with fulguration of the pedicle attaching the mass to
      the fallopian tube and removal of the dermoid cyst.

PMID- 16893545
TI  - Investigation of a variety of cationic surfactants attached to cation-exchange
      silica for hydrophobicity optimization in admicellar solid-phase extraction for
      high-performance liquid and gas chromatography.
AB  - A series of cationic surfactants were attached to cation-exchange silica that
      included silica modified with sulfopropyl groups and unmodified silica to create
      hydrophobic solid-phase extraction sorbents. Various chain lengths and chain
      numbers of amine, ammonium and pyridinium-based cationic surfactants were
      investigated to reach sufficient sorbent hydrophobicity to capture US
      Environmental Protection Agency (EPA) priority polycyclic aromatic hydrocarbons
      (PAHs). Of the tested surfactant/silica combinations, dihexadecyldimethylammonium
      cations attached to unmodified silica resulted in the sorbent having the greatest
      hydrophobicity. This sorbent provided strong hydrophobic attraction of PAHs and
      also efficient elution because the PAHs were removed together with the surfactant
      using a very mild 5% acetic acid in methanol rinse solution. This admicellar
      solid-phase extraction procedure was applied for the determination of these PAHs
      for both high-performance liquid and gas chromatography. The detection limits of
      these PAHs were below the EPA's maximum contaminant level of 0.2 microg/L.

PMID- 16893546
TI  - Application of sample disruption methods in the extraction of anthocyanins from
      solid or semi-solid vegetable samples.
AB  - Cassis, a commercial powder obtained from blackcurrant juice (Ribes nigrum L.),
      was used to optimize the anthocyanin extraction by matrix solid-phase dispersion
      (MSPD) and by sea sand disruption method (SSDM). The optimum eluent conditions
      were 5.0 mL of MeOH/H2O (1:1, v/v) at pH 2. The extracts were analyzed by HPLC
      with diode-array detection (DAD) and the extraction efficiency was evaluated by
      statistical comparison (analysis of variance, ANOVA-single factor) of the
      compounds peak areas. The extraction efficiency for the MSPD procedure was
      dependent on the chemical nature of the C18 material but the optimized procedure
      yielded results similar to those obtained by the inexpensive sea sand disruption
      method (SSDM). This procedure also compared favorably to a previously published
      liquid-liquid extraction method. The optimized sea sand method was then used in
      the anthocyanin extraction from red grapes (Vitis vinifera L.) and strawberries
      (Fragaria ananassa D.) yielding chromatographic profiles similar to those
      reported in the literature for these products.

PMID- 16893547
TI  - Authenticity of milk fat by fast analysis of triacylglycerols. Application to the
      detection of partially hydrogenated vegetable oils.
AB  - Detection of foreign fat in milk fat can be performed by analyzing
      triacylglycerols (TAGs) by gas-liquid chromatography (GLC) using the standardized
      methodology. The standard methodology recommends the use of a packed column,
      which allows the separation of milk TAGs according to their chain length (total
      carbon number). This procedure is not widely applied because these columns are
      not commercially available. This study describes a fast methodology by using a
      short apolar open-tubular capillary column. The developed experimental conditions
      can be used to obtain the chromatographic resolution required in the standardized
      procedure, and the separation of milk fat TAGs (C24 to C54) is achieved in less
      than 4 min. As indicated by the standardized method, the quantification was
      performed by calibration using the certified reference material CRM-519 butterfat
      as standard substance. The methodology was fully validated and relative
      repeatability values were compared with the values provided in the standardized
      procedure. The developed method was applied to detect adulteration of milk fat
      with partially hydrogenated vegetable oils (PHVOs). PHVOs contain variable amount
      of trans-18:1 acids and two different PHVOs having different trans-18:1 acid
      levels (13 and 38%) were added to milk fat at levels ranging from 5 to 30%. The
      obtained mixtures were analyzed by GLC and formulas established by the European
      Union were applied. Calculated S values indicated that PHVOs in milk fat could be
      analyzed at these levels. Approximate amounts of PHVOs added to the composite
      samples could be calculated using the standardized formula. The impact of
      adulteration of milk fat with PHVOs, which contains an important amount of trans
      9 and trans-10 18:1 acid isomers, was investigated as a complementary analytical
      criteria. We showed in composite samples, that the trans-18:1 acid isomeric
      distributions are distinct when referenced to the original milk fat profile and
      that trans-9 18:1 acid isomer is a good indicator of the occurrence of PHVOs in
      milk fat. Our results showed clearly that a short apolar capillary column can be
      used instead of a packed-column and that the mathematical model developed for the
      detection of foreign fat was suitable to detect adulteration of milk fat with
      PHVOs.

PMID- 16893548
TI  - Stereoisomer quantification of the beta-blocker drugs atenolol, metoprolol, and
      propranolol in wastewaters by chiral high-performance liquid chromatography
      tandem mass spectrometry.
AB  - A chiral liquid chromatography-tandem mass spectrometry (HPLC-MS-MS) method was
      developed and validated for measuring individual enantiomers of three beta
      blocker drugs (atenolol, metoprolol, and propranolol) in wastewater treatment
      plant (WWTP) influents and effluents. Mean recoveries of the pharmaceuticals
      ranged from 67 to 106%, and the limits of detection of the analytes were 2-17
      ng/L in wastewater effluents. The method was demonstrated by measuring, for the
      first time, the stereoisomer composition of target analytes in raw and treated
      wastewaters of two Canadian WWTPs. In these trials, racemic amounts of the three
      drugs were observed in influent of one wastewater treatment plant, but nonracemic
      amounts were observed in another. Effluents of the two plants contained
      nonracemic amounts of the drugs. These results indicate that biologically
      mediated stereoselective processes that differ among WWTPs had occurred to
      eliminate individual enantiomers of the target analytes.

PMID- 16893549
TI  - Analysis of eicosapentaenoic and docosahexaenoic acid geometrical isomers formed
      during fish oil deodorization.
AB  - Addition of long-chain polyunsaturated fatty acids (LC-PUFAs) from marine oil
      into food products implies preliminary refining procedures of the oil which
      thermal process affects the integrity of LC-PUFAs. Deodorization, the major step
      involving high temperatures, is a common process used for the refining of edible
      fats and oils. The present study evaluates the effect of deodorization
      temperature on the formation of LC-PUFA geometrical isomers. Chemically
      isomerized eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were used
      as reference samples. Fish oil samples have been deodorized at 180, 220 and 250
      degrees C for 3 h and pure EPA and DHA fatty acid methyl esters (FAMEs) were
      chemically isomerized using p-toluenesulfinic acid as catalyst. FAMEs prepared
      from fish oil were fractionated by reversed-phase high-performance liquid
      chromatography (RP-HPLC). Geometrical isomers produced by both processes were
      fractionated by silver-ion thin-layer chromatography (Ag-TLC) and silver-ion high
      performance liquid chromatography (Ag-HPLC). The FAME fractions were subsequently
      analyzed by gas chromatography (GC) on a 100 m highly polar
      cyanopropylpolysiloxane coated capillary column, CP-Sil 88. Our results show that
      thermally induced geometrical isomerization appears to be a directed reaction and
      some ethylenic double bond positions on the hydrocarbon chain are more prone to
      stereomutation. Only minor changes were observed in the EPA and DHA trans isomers
      content and distribution after deodorization at 180 degrees C. The analyses of
      EPA and DHA isomer fractions revealed that it is possible to quantify EPA
      geometrical isomers by GC using the described conditions. However, we notice that
      a mono-trans isomer of DHA, formed during both chemical and thermal treatments,
      co-elute with all-cis DHA. This feature should be taken into consideration for
      the quantification of DHA geometrical isomers.

PMID- 16893550
TI  - Soluble human leukocyte antigen: a diagnostic indicator of rheumatoid arthritis?
AB  - Early stage rheumatoid arthritis (RA) is often difficult to diagnose because
      initial symptoms are non-specific. To aid diagnosis, suitable serological
      diagnostic markers are sought. Elevated levels of soluble MHC class II (soluble
      human leukocyte antigen; sHLA-DR) in human serum have been associated with
      rheumatoid and 'rheumatoid-like' autoimmune diseases. As a result, sHLA-DR has
      been suggested as a specific marker of RA. However, reported levels of sHLA-DR in
      sera of healthy donors vary significantly and the mechanism of release of HLA-DR
      into serum is poorly understood. Investigations into the diagnostic potential of
      this molecule necessitate the development of a sensitive and specific sHLA-DR
      assay. We have investigated multiple ELISA setups to develop such an assay and
      false positive signal has been carefully removed using a combination of isotype
      matched controls and immuno-depletion. sHLA-DR levels in sera of RA patients were
      not significantly different from those in healthy donors which suggests sHLA-DR
      has limited utility in the diagnosis of RA. In RA patients, we detected high
      levels of sHLA-DR in aspirated synovial fluid (SF), but this did not correlate
      with sHLA-DR levels in serum.

PMID- 16893551
TI  - Gene delivery by dendrimers operates via different pathways in different cells,
      but is enhanced by the presence of caveolin.
AB  - In order to optimise and improve the efficacy of transfection mediated by
      dendrimers, it is essential to fully understand the mechanisms of cell entry and
      intracellular trafficking by these complexes. Previously, we have shown that gene
      delivery by dendrimers is dependent from cholesterol and membrane rafts. The
      inhibition of transfection by treatment with filipin III suggested that gene
      delivery might be occurring by a caveolin-dependent pathway. We therefore
      investigated the internalisation and transfection properties of dendriplexes
      using cell lines (HeLa and HepG2) that express few caveolae. We show that, in
      contrast to other cells, cholesterol depletion does not affect the ability of
      dendriplexes to transfect these cells. Inhibition of clathrin-independent,
      phagocytic and macropinocytic pathways also failed to inhibit transfection of
      these cells and endothelial cells. However, overexpression of caveolin 1 resulted
      in an increased rate of dendriplex uptake into HeLa, HepG2 and endothelial cells,
      and increased transfection efficiency. Furthermore, in endothelial cells,
      confocal microscopy demonstrated colocalisation of dendriplexes and caveolin 1.
      These data highlight that dendriplexes may use different internalisation pathways
      in different cells, and that caveolae form a preferential route for gene delivery
      by this non-viral vector.

PMID- 16893552
TI  - Gain of function in an ERV/ALR sulfhydryl oxidase by molecular engineering of the
      shuttle disulfide.
AB  - The ERV/ALR sulfhydryl oxidase domain is a versatile module adapted for catalysis
      of disulfide bond formation in various organelles and biological settings. Its
      four-helix bundle structure juxtaposes a Cys-X-X-Cys dithiol/disulfide motif with
      a bound flavin adenine dinucleotide (FAD) cofactor, enabling transfer of
      electrons from thiol substrates to non-thiol electron acceptors. ERV/ALR family
      members contain an additional di-cysteine motif outside the four-helix-bundle
      core. Although the location and context of this "shuttle" disulfide differs among
      family members, it is proposed to perform the same basic function of mediating
      electron transfer from substrate to the enzyme active site. We have determined by
      X-ray crystallography the structure of AtErv1, an ERV/ALR enzyme that contains a
      Cys-X4-Cys shuttle disulfide and oxidizes thioredoxin in vitro, and compared it
      to ScErv2, which has a Cys-X-Cys shuttle and does not oxidize thioredoxin at an
      appreciable rate. The AtErv1 shuttle disulfide is in a region of the structure
      that is disordered and thus apparently mobile and exposed. This feature may
      facilitate access of protein substrates to the shuttle disulfide. To test whether
      the shuttle disulfide region is modular and can confer on other enzymes oxidase
      activity toward new substrates, we generated chimeric enzyme variants combining
      shuttle disulfide and core elements from AtErv1 and ScErv2 and monitored
      oxidation of thioredoxin by the chimeras. We found that the AtErv1 shuttle
      disulfide region could indeed confer thioredoxin oxidase activity on the ScErv2
      core. Remarkably, various chimeras containing the ScErv2 Cys-X-Cys shuttle
      disulfide were found to function efficiently as well. Since neither the ScErv2
      core nor the Cys-X-Cys motif is therefore incapable of participating in oxidation
      of thioredoxin, we conclude that wild-type ScErv2 has evolved to repress activity
      on substrates of this type, perhaps in favor of a different, as yet unknown,
      substrate.

PMID- 16893553
TI  - Crystal structure of polymerization-competent actin.
AB  - All actin crystal structures reported to date represent actin complexed or
      chemically modified with molecules that prevent its polymerization. Actin cleaved
      with ECP32 protease at a single site between Gly42 and Val43 is virtually non
      polymerizable in the Ca-ATP bound form but remains polymerization-competent in
      the Mg-bound form. Here, a crystal structure of the true uncomplexed ECP32
      cleaved actin (ECP-actin) solved to 1.9 A resolution is reported. In contrast to
      the much more open conformation of the ECP-actin's nucleotide binding cleft in
      solution, the crystal structure of uncomplexed ECP-actin contains actin in a
      typical closed conformation similar to the complexed actin structures. This
      unambiguously demonstrates that the overall structure of monomeric actin is not
      significantly affected by a multitude of actin-binding proteins and toxins. The
      invariance of actin crystal structures suggests that the salt and precipitants
      necessary for crystallization stabilize actin in only one of its possible
      conformations. The asymmetric unit cell contains a new type of antiparallel actin
      dimer that may correspond to the "lower dimer" implicated in F-actin nucleation
      and branching. In addition, symmetry-related actin-actin contacts form a head to
      tail dimer that is strikingly similar to the longitudinal dimer predicted by the
      Holmes F-actin model, including a rotation of the monomers relative to each other
      not observed previously in actin crystal structures.

PMID- 16893554
TI  - Effects of the probiotic strain Lactobacillus johnsonii strain La1 on autonomic
      nerves and blood glucose in rats.
AB  - Oral administration of Lactobacillus casei reportedly reduces blood glucose
      concentrations in a non-insulin-dependent diabetic KK-Ay mouse model. In order to
      determine if other lactobacillus strains affect glucose metabolism, we evaluated
      the effect of the probiotic strain Lactobacillus johnsonii La1 (LJLa1) strain on
      glucose metabolism in rats. Oral administration of LJLa1 via drinking water for 2
      weeks inhibited the hyperglycemia induced by intracranial injection of 2-deoxy-D
      glucose (2DG). We found that the hyperglucagonemic response induced by 2DG was
      also suppressed by LJLa1. Oral administration of LJLa1 for 2 weeks also reduced
      the elevation of blood glucose and glucagon levels after an oral glucose load in
      streptozotocin-diabetic rats. In addition, we recently observed that
      intraduodenal injection of LJLa1 reduced renal sympathetic nerve activity and
      enhanced gastric vagal nerve activity, suggesting that LJLa1 might affect glucose
      metabolism by changing autonomic nerve activity. Therefore, we evaluated the
      effect of intraduodenal administration of LJLa1 on adrenal sympathetic nerve
      activity (ASNA) in urethane-anesthetized rats, since the autonomic nervous
      system, including the adrenal sympathetic nerve, may be implicated in the control
      of the blood glucose levels. Indeed, we found that ASNA was suppressed by
      intraduodenal administration of LJLa1, suggesting that LJLa1 might improve
      glucose tolerance by reducing glucagon secretion via alteration of autonomic
      nerve activities.

PMID- 16893555
TI  - The relationship between affective decision-making and theory of mind in the
      frontal variant of fronto-temporal dementia.
AB  - Structural brain imaging and neuropsychological data implicate the orbital
      aspects of prefrontal cortex in the developing neuropathology of fvFTD. Damage to
      this region is associated with deficient performance on laboratory tasks
      assessing theory of mind (ToM) and affective decision-making (DM), but the
      relationship between these two capacities in patients with prefrontal cortex
      dysfunction is unclear. We studied a group of patients with early/mild fvFTD
      (n=20) and a group of matched normal controls (n=10) on the Iowa gambling task
      (IGT) of affective decision-making, and the "reading the mind in the eyes" (MIE)
      and "faux pas" (FP) tests of ToM. The fvFTD group was impaired in both ToM tasks
      and the IGT. While performance measures from the two ToM tasks were significantly
      correlated, they were not associated with IGT performance. This suggests that
      whilst similar prefrontal circuitry is implicated in ToM and DM tasks, these
      cognitive domains may be independent. In clinical settings, the IGT may be useful
      as a complementary tool to the frontal test battery for patients with early/mild
      fvFTD. Deficits in decision-making and ToM observed in this study have distinct
      but additive effects upon the development of social behaviour in patients with
      prefrontal dysfunction.

PMID- 16893556
TI  - Hemispheric differences in the activation of perceptual information during
      sentence comprehension.
AB  - Previous research has suggested that perceptual information about objects is
      activated during sentence comprehension [Zwaan, R. A., Stanfield, R. A., &
      Yaxley, R. H. (2002). Language comprehenders mentally represent the shapes of
      objects. Psychological Science, 13(2), 168-171]. The goal in the current study
      was to examine the role of the two hemispheres in the activation of such
      information. Participants read sentences that conveyed information about the
      shape of an object (e.g., the egg was in the pan versus the egg was in the
      carton) and then received a picture of the object that was either consistent or
      inconsistent with the shape implied by the sentence (e.g., a fried egg versus a
      whole egg). In Experiment 1, pictures were presented briefly in either the left
      visual field or the right-visual field. Participants showed a mismatch effect,
      slower responses when the picture was inconsistent with the shape of the object
      implied by the sentence than when it was consistent, but only when the pictures
      appeared in the right-visual field (left hemisphere). In Experiment 2, the
      sentences were revised such that the shape of the object was described
      explicitly. Participants showed a mismatch effect in both visual fields. These
      findings suggest that the right hemisphere activates shape information during
      sentence comprehension when a shape description is explicit, whereas the left
      hemisphere activates such information both when the shape is described explicitly
      and when it is implied.

PMID- 16893557
TI  - Regioselective 2-hydroxylation of 17beta-estradiol by rat cytochrome P4501B1.
AB  - Previous work demonstrated that human cytochrome P4501B1 (CYP1B1) forms
      predominantly 4-hydroxyestradiol (4-OHE2), a metabolite which is carcinogenic in
      animal models. Here, we present results from kinetic studies characterizing the
      formation of 4-OHE2 and 2-hydroxyestradiol (2-OHE2) by rat CYP1B1 using 17beta
      estradiol (E2) as a substrate. Km and Kcat values were estimated using the
      Michaelis-Menten equation. For rat CYP1B1, the apparent Km values for the
      formation of 4-OHE2 and 2-OHE2 were 0.61+/-0.23 and 1.84+/-0.73 microM; the
      turnover numbers (Kcat) were 0.23+/-0.02 and 0.46+/-0.05 pmol/min/pmol P450; and
      the catalytic efficiencies (Kcat/Km) were 0.37 and 0.25, respectively. For human
      CYP1B1, the apparent Km values for the formation of 4-OHE2 and 2-OHE2 were 1.22+/
      0.25 and 1.10+/-0.26; the turnover numbers were 1.23+/-0.06 and 0.33+/-0.02; and
      the catalytic efficiencies were 1.0 and 0.30, respectively. The turnover number
      ratio of 4- to 2-hydroxylation was 3.7 for human CYP1B1 and 0.5 for rat CYP1B1.
      These results indicate that, although rat CYP1B1 is a low Km E2 hydroxylase, its
      product ratio, unlike the human enzyme, favors 2-hydroxylation. The Ki values of
      the inhibitor 2,4,3',5'-tetramethoxystilbene (TMS) for E2 4- and 2-hydroxylation
      by rat CYP1B1 were 0.69 and 0.78 microM, respectively. The Ki values of 7,8
      benzoflavone (alpha-NF) for E2 4- and 2-hydroxylation by rat CYP1B1 were 0.01 and
      0.02 microM, respectively. The knowledge gained from this study will support the
      rational design of CYP1B1 inhibitors and clarify results of CYP1B1 related
      carcinogenesis studies performed in rats.

PMID- 16893558
TI  - A new ELISA for determination of potency in snake antivenoms.
AB  - A competitive ELISA for potency determination of bothropic equine antivenom was
      developed and compared to the conventional in vivo ED(50) assay, with the aim of
      partially substituting the in vivo assay in the monitoring of antivenom
      immunoglobulin levels. On this purpose, blood samples were taken at different
      times during and after the immunization protocol of the lot of horses used for
      production of snake antivenom at the Instituto de Higiene, Uruguay. Both the
      competitive ELISA and the ED(50) assay were performed on those samples. In
      addition, a group of five commercial pepsin-digested antivenoms were tested by
      both methods. A significant (P<0.001) correlation (Pearson's r=0.957) was found
      between the ELISA titres and the corresponding ED(50) values, indicating that the
      in vitro test can estimate the neutralizing antibody capacity of the sera as well
      as the in vivo assay. By means of this new ELISA, it was found that the immunized
      animals maintained good venom antibody titres, in the order of 20-50% of the
      maximum achieved, even 10 month after the end of the immunization schedule. The
      main advantage of our ELISA design is its ability to correctly estimate the
      neutralization capacity of crude hyperimmune plasma and antivenom sera
      independently of their antibody composition in terms of whole IgG or F(ab')(2)
      fragment.

PMID- 16893559
TI  - DEAMOX--new biological nitrogen removal process based on anaerobic ammonia
      oxidation coupled to sulphide-driven conversion of nitrate into nitrite.
AB  - This paper reports about the successful laboratory testing of a new nitrogen
      removal process called DEAMOX (DEnitrifying AMmonium OXidation) for treatment of
      typical strong nitrogenous wastewater such as baker's yeast effluent. The concept
      of this process combines the recently discovered anammox (anaerobic ammonium
      oxidation) reaction with autotrophic denitrifying conditions using sulphide as an
      electron donor for the production of nitrite from nitrate within an anaerobic
      biofilm. To generate sulphide and ammonia, a Upflow Anaerobic Sludge Bed (UASB)
      reactor was used as a pre-treatment step. The UASB effluent was split and
      partially fed to a nitrifying reactor (to generate nitrate) and the remaining
      part was directly fed to the DEAMOX reactor where this stream was mixed with the
      nitrified effluent. Stable process performance and volumetric nitrogen loading
      rates of the DEAMOX reactor well above 1000 mgN/l/d with total nitrogen removal
      efficiencies of around 90% were obtained after long-term (410 days) optimisation
      of the process. Important prerequisites for this performance are appropriate
      influent ratios of the key species fed to the DEAMOX reactor, namely influent N
      NO(x)/N-NH(4) ratios >1.2 (stoichiometry of the anammox reaction) and influent S
      H(2)S/N-NO(3) ratios >0.57 mgS/mgN (stoichiometry of the sulphide-driven
      denitrification of nitrate to nitrite). The paper further describes some
      characteristics of the DEAMOX sludge as well as the preliminary results of its
      microbiological characterisation.

PMID- 16893560
TI  - Piggery wastewater treatment using Alcaligenes faecalis strain No. 4 with
      heterotrophic nitrification and aerobic denitrification.
AB  - Alcaligenes faecalis strain No. 4, which has heterotrophic nitrification and
      aerobic denitrification abilities, was used to treat actual piggery wastewater
      containing high-strength ammonium under aerobic conditions. In a continuous
      experiment using a solids-free wastewater (SFW) mixed with feces, almost all of
      the 2000 NH4+ -N mg/L and 12,000 COD mg/L in the wastewater was removed and the
      ammonium removal rate was approximately 30 mg-N/L/h, which was 5-10 times higher
      than the rates achieved by other bacteria with the same abilities. The
      denitrification ratio was more than 65% of removed NH4+ -N, indicating that
      strain No. 4 exhibited its heterotrophic nitrification and aerobic
      denitrification abilities in the piggery wastewater.

PMID- 16893561
TI  - Age-related changes of mitochondrial structure and function in Caenorhabditis
      elegans.
AB  - A number of observations have been made to examine the role that mitochrondrial
      energetics and superoxide anion production play in the aging of wild-type
      Caenorhabditis elegans. Ultrastructural analyses reveal the presence of swollen
      mitochondria, presumably produced by fusion events. Two key mitochondrial
      functions - the activity of two electron transport chain complexes and oxygen
      consumption - decreased as animals aged. Carbonylated proteins, one byproduct of
      oxidative stress, accumulated in mitochondria much more than in the cytoplasm.
      This is consistent with the notion that mitochondria are the primary source of
      endogenous reactive oxygen species. However, the level of mitochondrially
      generated superoxide anion did not change significantly during aging, suggesting
      that the accumulation of oxidative damage is not due to excessive production of
      superoxide anion in geriatric animals. In concert, these data support the notion
      that the mitochondrial function is an important aging determinant in wild-type C.
      elegans.

PMID- 16893562
TI  - Immunocytochemical study of cytoskeletal proteins in centronuclear myopathies.
AB  - The developmental status of muscle fibers was investigated in three cases of
      myotubular myopathy: one infant with the X-linked recessive form and two adult
      brothers with the autosomal, probably recessive, form of the disease. The
      presence of the developmentally regulated proteins desmin, vimentin and
      dystrophin was investigated by immunocytochemistry with the use of monoclonal
      antibodies. In the X-linked case, intense immunolabelling for vimentin and desmin
      was observed in the nuclear area of a great number of muscle fibers, while a few
      others showed sarcoplasmic dystrophin immunolabelling or were dystrophin
      negative. In the adult cases, strong desmin immunoreactivity was observed, but
      only a few fibers labelled for vimentin. Dystrophin sarcolemmal immunolabelling
      was normal, but in some fibers dystrophin was observed in the area of the central
      nucleus. These findings are supportive of a maturational arrest of muscle fibers
      in the X-linked cases and possibly indicative of a similar mechanism in the adult
      form of centronuclear myopathy in these patients.

PMID- 16893563
TI  - Panavia F 2.0 bonding to contaminated zirconia ceramic after different cleaning
      procedures.
AB  - OBJECTIVES: The purpose of this laboratory study was to evaluate the influence of
      different cleaning methods after saliva contamination and after using a silicone
      disclosing medium on the resin bond strength to zirconia ceramic. The hypothesis
      was that the resin-ceramic bond strength and its durability are related to the
      ceramic surface condition. METHODS: Plexiglas tubes filled with composite resin
      were bonded to air-abraded zirconia ceramic disks using a phosphate monomer
      containing composite resin. Four surface cleaning methods were used after
      contaminating the ceramic surface: air abrasion with 50 mum Al(2)O(3) at 2.5 bar
      pressure for 15s, cleaning with 37% phosphoric acid for 60s once or for 30s
      twice, or cleaning in 96% isopropanol for 15s. The specimens of the control group
      were not cleaned after using the silicone disclosing medium. For each combination
      16 specimens were bonded in an alignment apparatus. Subgroups of eight bonded
      specimens were tested for tensile bond strength (TBS) after storage for either 3
      or 150 days combined with 37,500 thermal cycles. The statistical analyses were
      performed with the Kruskal-Wallis test, followed by multiple pair-wise
      comparisons using the Wilcoxon rank sum test. RESULTS: The mean TBS ranged from
      6.6 to 49.9 MPa after 3 days and from 0 to 19.8 MPa after 150 days. Air abrasion
      of the ceramic surface provided statistically significantly higher bond strengths
      than the other cleaning methods after 3 and 150 days. Alcohol cleaning of the
      ceramic did not provide durable bond strengths over time. SIGNIFICANCE: Ceramic
      cleaning methods after try-in procedures have a significant influence on the
      resin-ceramic bond strength. Air abrasion of contaminated zirconia ceramic is the
      most effective.

PMID- 16893564
TI  - Sulfated chitin and chitosan as novel biomaterials.
AB  - Chitin and chitosan are known to be natural polymers and they are non-toxic,
      biodegradable and biocompatible. Chemical modification of chitin and chitosan
      with sulfate to generate new bifunctional materials is of interest because the
      modification would not change the fundamental skeleton of chitin and chitosan,
      would keep the original physicochemical and biochemical properties and finally
      would bring new or improved properties. The sulfated chitin and chitosan have a
      variety of applications, such as, adsorbing metal ions, drug delivery systems,
      blood compatibility, and antibacterial field. The purpose of this review is to
      take a closer look about the different synthetic methods and potential
      applications of sulfated chitin and chitosan. Based on current research and
      existing products, some new and futuristic approaches in this context area are
      discussed in detail. From the studies reviewed, we concluded that sulfated chitin
      and chitosan are promising materials for biomedical applications.

PMID- 16893565
TI  - Modification of the biopolymer castor oil with free isocyanate groups to be
      applied as bioadhesive.
AB  - Surgical adhesives have been used for several applications, including
      haemostasis, sealing air leakages and tissue adhesion. The aim of this work was
      to develop a biodegradable urethane-based bioadhesive containing free isocyanate
      groups. This material presents the advantage of being biodegradable,
      biocompatible and having the capacity of reacting with amino groups present in
      the biological molecules. A urethane based on castor oil (CO) was synthesized by
      reaction of the molecule with isophorone diisocyanate (IPD). The characterization
      of the material was accomplished by different techniques: ATR-FT-IR (attenuated
      transmittance reflection-Fourier transform infrared), swelling capacity
      determination, evaluation of the moisture curing kinetics, reaction with aminated
      substrates and determination of surface energy by contact angle measurement. The
      study of the urethane thermal properties was performed by DMTA (dynamical
      mechanical thermal analysis) and TGA (thermogravimetric analysis). The
      haemocompatibility of the urethane was also evaluated by thrombosis and
      haemolysis tests.

PMID- 16893566
TI  - Extracellular matrix remodeling--methods to quantify cell-matrix interactions.
AB  - Tissue turnover during wound healing, regeneration or integration of biomedical
      materials depends on the rate and extent of materials trafficking into and out of
      cells involved in extracellular matrix (ECM) remodeling. To exploit these
      processes, we report the first model for matrix trafficking in which these issues
      are quantitatively assessed for cells grown on both native collagen (normal
      tissue) and denatured collagen (wound state) substrates. Human fibroblasts more
      rapidly remodeled denatured versus normal collagen type I to form new ECM. Fluxes
      to and from the cells from the collagen substrates and the formation of new ECM
      were quantified using radioactively labeled substrates. The model can be employed
      for the systematic and quantitative study of the impact of a broad range of
      physiological factors and disease states on tissue remodeling, integrating
      extracellular matrix structures and cell biology.

PMID- 16893567
TI  - Molecular analysis of the 21-kb bacteriocin-encoding plasmid pEF1 from
      Enterococcus faecium 6T1a.
AB  - The complete 21,344-bp DNA sequence of the bacteriocin-encoding plasmid pEF1 from
      Enterococcus faecium 6T1a was determined. Thirty-four putative open reading
      frames which could code for proteins longer than 42 amino acids were found. Those
      included the structural genes encoding for the previously described bacteriocins
      enterocin I and J (also named as enterocins L50A and L50B). After comparison to
      sequences in public databases, analysis of the gene organization of pEF1 suggests
      a modular structure with three different functional domains: the replication
      region, the bacteriocin region and the mobilization plus UV-resistance region.
      This genetic mosaic structure most probably evolved through recombination events
      promoted by transposable elements. The hypothesis that the bacteriocin cluster on
      pEF1 could act as a functional plasmid stabilization module in E. faecium 6T1a is
      discussed.

PMID- 16893568
TI  - Antigen three-dimensional structure guides the processing and presentation of
      helper T-cell epitopes.
AB  - Antigen three-dimensional structure potentially controls presentation of CD4(+) T
      cell epitopes by limiting the access of proteolytic enzymes and MHC class II
      antigen-presenting proteins. The protease-sensitive mobile loops of Hsp10s from
      mycobacteria, Escherichia coli, and bacteriophage T4 (T4Hsp10) are associated
      with adjacent immunodominant helper T-cell epitopes, and a mobile-loop deletion
      in T4Hsp10 eliminated the protease sensitivity and the associated epitope
      immunodominance. In the present work, protease-sensitivity and epitope
      presentation was analyzed in a group of T4Hsp10 variants. Two mobile-loop
      sequence variants of T4Hsp10 were constructed by replacing different segments of
      the mobile loop with an irrelevant sequence from hen egg lysozyme. The variant
      proteins retained native-like structure, and the mobile loops retained protease
      sensitivity. Mobile-loop deletion and reconstruction affected the presentation of
      two epitopes according to whether the epitope was protease-independent or
      protease-dependent. The protease-independent epitope lies within the mobile loop,
      and the protease-dependent epitope lies in a well-ordered segment on the carboxy
      terminal flank of the mobile loop. The results are consistent with a model for
      processing of the protease-dependent epitope in which an endoproteolytic nick in
      the mobile-loop unlocks T4Hsp10 three-dimensional structure, and then the epitope
      becomes available for binding to the MHC protein.

PMID- 16893569
TI  - Minimal depression and vision function in age-related macular degeneration.
AB  - OBJECTIVE: To evaluate the impact of minimal depression on subjective and
      objective vision function measures in age-related macular degeneration (AMD).
      DESIGN: Prospective cross-sectional study. PARTICIPANTS: Two hundred six
      outpatients with newly diagnosed neovascular AMD in one eye and preexisting AMD
      in the fellow eye. METHODS: Structured clinical evaluations of visual acuity
      (VA), contrast sensitivity, vision function, and depression. MAIN OUTCOME
      MEASURES: The 17-item National Eye Institute Visual Function Questionnaire (NEI
      VFQ 17), Melbourne Low-Vision Index (MLVI), Chronic Disease Score, and Hamilton
      Depression Rating Scale. RESULTS: Minimally depressed subjects had significantly
      worse vision function on both the NEI VFQ 17 and performance-based tasks of the
      MLVI than nondepressed subjects, independent of severity of VA, contrast
      sensitivity, and medical status. CONCLUSIONS: Minimally depressed patients with
      AMD, who would not be considered depressed according to current diagnostic
      standards, suffer decrements in vision function that cannot be accounted for by
      the severity of their eye disease or general medical problems. These data
      emphasize the need to assess depressive symptoms in research studies that use
      vision function outcome measures and in clinical practice to identify excess
      vision-related disability in patients with AMD.

PMID- 16893570
TI  - Methods for the determination of intracellular levels of ribose phosphates.
AB  - Ribose phosphates are either synthesized through the oxidative branch of the
      pentose phosphate pathway or stem from the phosphorolytic cleavage of the N
      glycosidic bond of ribonucleosides. The two major pentose phosphates, ribose-5
      phosphate and ribose-1-phosphate, can be readily interconverted by
      phosphopentomutase. Ribose-5-phosphate is also the direct precursor of 5
      phosphoribosyl-1-pyrophosphate, which is used for both de novo and salvage
      synthesis of nucleotides. On the other hand, the phosphorolysis of
      deoxyribonucleosides is the major source of deoxyribose phosphates. While the
      destiny of the nucleobase stemming from nucleoside phosphorolysis has been
      extensively investigated, the fate of the sugar moiety has been somehow
      neglected. However, extensive advances have been made in elucidating the pathways
      by which the pentose phosphates, arising from nucleoside phosphorolysis, are
      either recycled, without opening of their furanosidic ring, or catabolized as a
      carbon and energy source. Nevertheless, many aspects of pentose phosphate
      metabolism, and the possible involvement of these compounds in a number of
      cellular processes still remain obscure. The comprehension of the role played by
      pentose phosphates may be greatly facilitated by the knowledge of their steady
      state intracellular levels and of their changes in response to variations of
      intra- and extracellular signals.

PMID- 16893572
TI  - Diversified serum IgG response involving non-myelin CNS proteins during
      experimental autoimmune encephalomyelitis.
AB  - We sequentially analyzed the serum IgG response against normal mouse brain during
      experimental autoimmune encephalomyelitis in SJL/J mice injected with CFA,
      Bordetella pertussis toxin (BPT) and proteolipid protein 139-151 peptide,
      compared with mice that received CFA and BPT or were uninjected. Dynamic changes
      were observed from day 0 to day 28 in the 3 groups. Six highly discriminant
      antigenic bands (kappa=0.974) were identified. Three non-myelin proteins were
      characterized (mitochondrial aconitase hydratase 2, phosphoglycerate mutase 1,
      brain specific pyruvate deshydrogenase). The IgG response against two of them was
      less frequent in EAE whereas it was associated with multiple sclerosis in our
      previous work.

PMID- 16893571
TI  - Clinical features and correlates of major depressive disorder in individuals with
      body dysmorphic disorder.
AB  - BACKGROUND: Body dysmorphic disorder (BDD) and major depressive disorder (MDD)
      appear highly comorbid. However, MDD in individuals with BDD has received little
      investigation. METHODS: The prevalence and characteristics of comorbid MDD were
      assessed in 178 BDD subjects. BDD subjects with current comorbid MDD (n=68) were
      compared to BDD subjects without current comorbid MDD (n=96) on demographic and
      clinical characteristics. Predictors of current MDD were determined using
      logistic regression. RESULTS: 74.2% of subjects had lifetime MDD, and 38.2% had
      current MDD. The melancholic subtype was most common, and a majority of depressed
      subjects had recurrent episodes. Mean onset of BDD occurred at a younger age than
      MDD. Subjects with current comorbid MDD had many similarities to those without
      MDD, although those with comorbid MDD had more severe BDD. Subjects with comorbid
      MDD were also more likely to have an anxiety or personality disorder, as well as
      a family history of MDD. They also had greater social anxiety, suicidality, and
      poorer functioning and quality of life. Current MDD was independently predicted
      by a personality disorder and more severe BDD. LIMITATIONS: It is unclear how
      generalizable the results are to the community or to subjects ascertained for MDD
      who have comorbid BDD. The study lacked a comparison group such as MDD subjects
      without BDD. CONCLUSIONS: MDD is common in individuals with BDD. Individuals with
      current MDD had greater morbidity in some clinically important domains, including
      suicidality, functioning, and quality of life. A personality disorder and more
      severe BDD independently predicted the presence of current MDD.

PMID- 16893574
TI  - European Brain Council: partnership to promote European and national brain
      research.

PMID- 16893573
TI  - A TaqMan real-time RT-PCR for quantifying Mourilyan virus infection levels in
      penaeid shrimp tissues.
AB  - A highly sensitive and specific TaqMan real-time quantitative RT-PCR (qRT-PCR)
      was developed to detect and quantify Mourilyan virus (MoV), a newly described
      bunya-like virus of penaeid shrimp. The PCR primers and TaqMan probe targeted a
      67-nucleotide (nt) sequence in the MoV M RNA segment. Using dilution series of a
      849 nt RNA transcribed in vitro from cDNA clone pMoV4.1, the assay could detect
      down to a single MoV RNA equivalent, reliably detected 10 RNA copies and had a
      log linear range up to 1 x 10(9) RNA copies. In experimentally infected Penaeus
      japonicus shrimp, the test was used to quantify increases in MoV loads over time
      in hemocytes, lymphoid organ and gills. Sequential increases in MoV RNA copy
      numbers occurred in lymphoid organ and gill tissues collected at 6, 24 and 48 h
      post-infection. However, RNA copy numbers decreased slightly in hemocytes sampled
      at 48 h compared to 24 h. The qRT-PCR data correlated well with amplicon yields
      generated using a conventional RT-nested PCR targeting the same MoV RNA segment.
      Moreover, histology and in situ hybridisation using shrimp cephalothorax sections
      identified increases in lymphoid organ spheroid numbers and confirmed that
      increases in MoV RNA detected in lymphoid organ tissue were due to expansion in
      the numbers of infected cells. The qRT-PCR assay should find use in high
      throughput screening applications to detect MoV in broodstock and postlarvae used
      for culture or breeding purposes and for tracking changes in infection levels
      during shrimp grow-out.

PMID- 16893575
TI  - Influence of acute and sub-chronic nicotine pretreatment on morphine state
      dependent learning.
AB  - In the present study, the effects of acute and sub-chronic pretreatment of
      nicotine on impairment of memory formation and the state-dependent learning by
      morphine have been investigated in mice. Pre-training administration of morphine
      (5mg/kg) decreased the learning of a one-trial passive avoidance task, which was
      reversed by pre-test administration of the same dose of morphine. Amnesia induced
      by pre-training morphine was also significantly reversed in nicotine (0.001, 0.01
      and 0.1 mg/kg)-treated animals on the test day. Morphine induced amnesia was also
      reversed in animals which had previously received sub-chronic injections of
      nicotine, once daily for 3 days followed by 14 days of no drug treatment. The
      restoration of memory by pre-test morphine was also reduced in animals which had
      previously received once daily injections of atropine (0.25, 0.5 and 1 mg/kg,
      i.p.) for 3 days after 14 of being days drug free. In the animals, restoration of
      memory by sub-chronic nicotine administration, was also decreased by once daily
      administration of atropine (0.25, 0.5 and 1 mg/kg) 10 min prior to injection of
      nicotine (0.1 microg/kg/day, for 3 days) but not with SCH 23390; R(+)-7-chloro-8
      hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine HCl (0.01, 0.05 and
      0.1 mg/kg) or sulpiride (25, 50 and 100 mg/kg) during 3-days of treatment with
      nicotine. The results suggest that nicotine may induce sensitization which
      affects the impairment of memory formation via cholinergic but not dopaminergic
      systems.

PMID- 16893576
TI  - Aneurysm of circumflex coronary artery caused by cardiac vein and fistulous
      connection to the left ventricle identified on MDCT.

PMID- 16893577
TI  - The utility of different definitions of metabolic syndrome in Andean population.

PMID- 16893578
TI  - The role of intravenous immunoglobulin in the treatment of chronic heart failure.
AB  - Chronic heart failure (HF), including both ischemic and idiopathic dilated
      cardiomyopathies, is accompanied by a dysregulated cytokine network characterized
      not only by a rise in inflammatory cytokines, but also by an inadequate elevation
      of anti-inflammatory mediators. This dysregulation has been implicated in the
      development and progression of chronic HF, and in the last decade, attempts have
      been made to modulate this persistent inflammation. Failure of anti-tumor
      necrosis factor therapy in HF has led to further interest in a more general
      immunomodulatory approach, directed against the inflammatory imbalance rather
      than one particular cytokine. Treatment with intravenous immunoglobulin (IVIg)
      may represent such a broad-based approach trying to restore the dysregulated
      cytokine network through various mechanisms such as Fc receptor blockade,
      neutralization of microbial antigens and superantigens and more direct anti
      inflammatory effects on the cytokine network. However, although one randomized
      placebo-controlled study in patients with chronic HF showed that IVIg improved
      left ventricular ejection fraction, accompanied by anti-inflammatory net effects,
      IVIg had no effect in another placebo-controlled study examining the effect of
      this medication in recent-onset cardiomyopathy. So far, few patients have been
      included in clinical trials, and there is clearly a need for larger placebo
      controlled mortality studies involving a diverse group of patients with regard to
      cause and severity of HF.

PMID- 16893579
TI  - Pulmonary function at peak exercise in patients with chronic heart failure.
AB  - BACKGROUND: Various respiratory abnormalities are associated with chronic heart
      failure (CHF). However, changes in inspiratory capacity (IC) and breathing
      pattern from rest to exercise in patients with CHF have not been thoroughly
      investigated in these patients. MATERIALS AND METHODS: Seventy seven (66 male/11
      female) patients with clinical stable CHF (age: 52+/-11 years) were studied. All
      the patients underwent pulmonary function tests, including measurements of IC and
      maximal inspiratory pressure (Pimax) at rest and then a maximal cardiopulmonary
      exercise testing (CPET) on a treadmill. During the CPET, IC was measured every 2
      min. Pimax was measured again after the end of CPET. RESULTS: Percent predicted
      forced expiratory volume in 1 s (FEV1) was 91+/-12, %predicted forced vital
      capacity (FVC) was 92+/-13, %FEV1/FVC was 81+/-4, and %predicted IC was 85+/-18.
      Peak exercise IC was lower than resting (2.4+/-0.6 vs. 2.6+/-0.6 l, p<0.001).
      Analysis of variance between Weber's groups revealed statistically significant
      differences in peak exercise IC (p<0.001), VE/VCO2slope (p<0.001), resting Pimax
      (p=0.005) and post-exercise Pimax (p<0.001). At rest, there was a statistically
      significant difference in end-tidal CO2 (P(ETCO2)) (p=0.002), in breathing
      frequency (p=0.004), in inspiratory time (Ti) (p=0.04) and in total respiratory
      time (T(Tot)) (p=0.004) among Weber's groups. At peak exercise there was a
      statistically significant decrease in minute ventilation (VE) (p<0.001), tidal
      volume (VT) (p<0.001), respiratory cycle (VT/TI) (p<0.001) and P(ETCO2)
      (p<0.001). Peak IC was correlated with peak VO2 (r=0.72, p<0.001), anaerobic
      threshold (r=0.71, p<0.001), VO2/t slope (r=0.54, p<0.0001), and post-exercise
      Pimax (r=0.62, p<0.001). CONCLUSIONS: In patients with CHF, peak exercise IC is
      reduced in parallel with disease severity, which is probably due to respiratory
      muscle dysfunction.

PMID- 16893580
TI  - What is the plausible strategy for the management of patients with isolated
      coronary artery ectasia and myocardial ischemia?

PMID- 16893581
TI  - Does managed health care reduce health care disparities between minorities and
      Whites?
AB  - This paper investigates whether managed care ameliorates or aggravates ethnic and
      racial health care disparities in Medicare. First, we analyze the choice of type
      of insurance made by Medicare enrollees to see if minorities are more likely to
      choose the managed care alternative. Second, we study the differential effect of
      managed care on disparities using several measures of access, use and cost of
      services. Both analyses are conducted on two independent data sets, the Medicare
      Current Beneficiary Survey and the National Health Interview Survey. We conclude
      that relative to Whites, minorities are at least as well off -- in terms of
      benefits and costs -- in Medicare managed care as in Medicare traditional
      indemnity plans.

PMID- 16893582
TI  - Scale-up of recombinant Opc protein production in Escherichia coli for a
      meningococcal vaccine.
AB  - Opc is an outer membrane protein from Neisseria meningitidis present in
      meningococcal vaccine preparations. The opc gene, codifying for this protein, was
      cloned in to Escherichia coli and the Opc protein was expressed under the control
      of a tryptophan promoter. The recombinant strain was grown in batch cultures. Opc
      was expressed as inclusion bodies at about 32% of the total cellular protein. We
      examined the scale-up culture conditions for the production of the recombinant
      Opc. The scale-up process was performed from 1.5 l to 50 l culture, using first,
      the constant power per unit of volume (P/V) as main scaling criteria, and then
      the oxygen mass transfer coefficient (K(L)a) scaling criteria to adjust the
      optimal aeration conditions. A final productivity of 52 mgl(-1)h(-1) was obtained
      at the 50l culture scale compared with the 49 mgl(-1)h(-1) productivity at 1.5l
      laboratory scale.

PMID- 16893583
TI  - Directed evolution of the thermostable xylanase from Thermomyces lanuginosus.
AB  - The thermostability of the endo-beta-1,4-xylanase from Thermomyces lanuginosus
      (xynA) was improved by directed evolution using error-prone PCR. Transformants
      expressing the variant xylanases were first selected on 0.4% Remazol Brilliant
      Blue-xylan and then exposed to 80 degrees C. Whereas the wild type XynA lost 90%
      activity after 10 min at 80 degrees C, five mutants displayed both higher
      stabilities and activities than XynA. Four mutants were subjected to further
      mutagenesis to improve the stability and activity of the xylanase. Subsequent
      screening revealed three mutants with enhanced thermostability. Mutant 2B7-10
      retained 71% of its activity after treatment at 80 degrees C for 60 min and had a
      half-life of 215 min at 70 degrees C, which is higher than that attained by XynA.
      Sequence analysis of second generation mutants revealed that mutations were not
      concentrated in any particular region of the protein and exhibited much
      variation. The best mutant obtained from this study was variant 2B7-10, which had
      a single substitution (Y58F) in beta-sheet A of the protein, which is the
      hydrophilic, solvent-accessible outer surface of the enzyme. Most of the mutants
      obtained in this study displayed a compromise between stability and activity, the
      only exception being mutant 2B7-10. This variant showed increased activity and
      thermostability.

PMID- 16893584
TI  - High prevalence of albuminuria in population-based patients diagnosed with type 2
      diabetes in the Shanghai downtown.
AB  - OBJECTIVE: The prevalence of albuminuria and the risk factors associated with
      albuminuria were evaluated among the Chinese patients diagnosed with type 2
      diabetes aged over 30 in the Shanghai downtown. We also evaluated the variability
      of urinary albumin-to-creatinine ratio (ACR) among the three measurements and the
      relationship between diabetic retinopathy (DR) and albuminuria. METHODS: The 1039
      Chinese patients diagnosed with type 2 diabetes aged over 30 were investigated by
      randomized cluster sampling in the Shanghai downtown and 1018 patients were
      analyzed in this study. Body mass measurements including height, weight, waist
      circumference and hip circumference, resting blood pressure, fasting blood
      measures, urinary ACR and the digitally stored fundus images were investigated.
      The prevalence of albuminuria was calculated and the risk factors associated with
      albuminuria were evaluated by stepwise logistic regression. The concordance of
      urinary ACR was evaluated by observed agreement. The relationship between
      albuminuria and DR was also evaluated. RESULTS: (1) The mean age of all patients
      was 66.10+/-11.54 years and the duration of diabetes was 7.89+/-7.16 years. (2)
      The prevalence of albuminuria was 49.6% among the Chinese patients diagnosed with
      type 2 diabetes aged over 30 in the Shanghai downtown, 41.4% with
      microalbuminuria and 8.2% with macroalbuminuria. (3) Microalbuminuria was
      significantly associated with systolic blood pressure, gender and waist
      circumference. Macroalbuminuria was significantly associated with systolic blood
      pressure and duration of diabetes. (4) Observed agreement among the three urinary
      ACR measurement for albuminuria staging was 73.3% (first versus second), 64.5%
      (first versus third) and 77.5% (second versus third). Observed agreement in the
      albuminuria staging between the single urinary ACR measurement and all three
      urinary ACR measurements was 85.8% (first versus all three), 87.6% (second versus
      all three) and 81.9% (third versus all three). (5) The percentage of DR in the
      macroalbuminuric group (59.2%) was significantly higher than that in the
      normalbuminuria group (16.1%) and microalbuminuria group (24.6%). (6) The
      macroalbuminuric patients with DR had significantly increased fasting blood
      glucose and HbA1c compared with the macroalbuminuric patients without DR.
      CONCLUSION: The prevalence of microalbuminuria observed in the Chinese patients
      diagnosed with type 2 diabetes aged over 30 in the Shanghai downtown reached up
      to 41.4% though the observations in our study might be representative of the
      diabetic patients of the Shanghai downtown. We agreed that at least two of the
      three urinary collections were done in a 3- to 6-month period because of the day
      to-day variability in albumin excretion. The percentage of DR among the patients
      with macroalbuminuria was 59.2%, and the macroalbuminuric patients with the
      significantly high plasma glucose and DR were prone to diagnose DN.

PMID- 16893586
TI  - Globalization and the trends of medical technology trade in Turkey.
AB  - Medical technology trade is one of the most affected health areas by global
      regulations in the developing countries. The aim of the study is to examine
      recent changes in medical technology import and export and their results in
      Turkey. Data show that the total medical technology imports (MTI) increased from
      $ 34.6 million to $ 3427.9 million between 1970 and 2003. While MTI constituted
      3.6% of total imports in 1970 and 1.3% in 1980, this ratio raised up to 4.9% in
      2003. The ratio of MTI in total health expenditures were also increased from 7.6%
      in 1970 to 31.5% in 2003. Medical technology exports (MTE) have been increased
      from $ 0.9 million in 1970 to $ 303.2 million in 2003. The ratio of MTE to MTI
      increased from 2.7% to 13.9% between 1970 and 1990 and decreased after 1990, to
      8.8%. Our study implied that the medical technology trade in Turkey has been
      negatively affected and in some respects differs from some other important
      industries in the globalization era. Nevertheless, detailed comparative studies
      in different developing countries such as China, Brazil, Mexico and India, are
      needed to explore the real state of medical technology trade, use and the effects
      of globalization on these topics.

PMID- 16893587
TI  - Microarray-MD: a system for exploratory analysis of microarray gene expression
      data.
AB  - In this paper, we present Microarray Medical Data explorer (Microarray-MD), a
      novel software system that is able to assist in the exploratory analysis of gene
      expression microarray data. It implements a combination scheme of multiple
      Support Vector Machines, which integrates a variety of gene selection criteria
      and allows for the discrimination of multiple diseases or subtypes of a disease.
      The system can be trained and automatically tune its parameters with the
      provision of pathologically characterized gene expression data to its input.
      Given a set of new, uncharacterized, patient's data as input, it outputs a
      decision on the type or the subtype of a disease. A graphical user interface
      provides easy access to the system operations and direct adjustment of its
      parameters. It has been tested on various publicly available datasets. The
      overall accuracy it achieves was estimated to exceed 90%.

PMID- 16893588
TI  - Rough set feature selection and rule induction for prediction of malignancy
      degree in brain glioma.
AB  - The degree of malignancy in brain glioma is assessed based on magnetic resonance
      imaging (MRI) findings and clinical data before operation. These data contain
      irrelevant features, while uncertainties and missing values also exist. Rough set
      theory can deal with vagueness and uncertainty in data analysis, and can
      efficiently remove redundant information. In this paper, a rough set method is
      applied to predict the degree of malignancy. As feature selection can improve the
      classification accuracy effectively, rough set feature selection algorithms are
      employed to select features. The selected feature subsets are used to generate
      decision rules for the classification task. A rough set attribute reduction
      algorithm that employs a search method based on particle swarm optimization (PSO)
      is proposed in this paper and compared with other rough set reduction algorithms.
      Experimental results show that reducts found by the proposed algorithm are more
      efficient and can generate decision rules with better classification performance.
      The rough set rule-based method can achieve higher classification accuracy than
      other intelligent analysis methods such as neural networks, decision trees and a
      fuzzy rule extraction algorithm based on Fuzzy Min-Max Neural Networks (FRE
      FMMNN). Moreover, the decision rules induced by rough set rule induction
      algorithm can reveal regular and interpretable patterns of the relations between
      glioma MRI features and the degree of malignancy, which are helpful for medical
      experts.

PMID- 16893589
TI  - Generating psychotropic drug exposure data from computer-based medical records.
AB  - PURPOSE: To develop a methodology for extracting psychotropic drug exposure data
      from computer-based medical records and for generating drug exposure variables
      suitable for secondary use. METHODS: In South-Verona, Italy, a registry including
      every patient receiving psychotropic medications is operating since 2004. The
      basic structure of the registry is the medication record. Each record stores data
      on a specific prescription, and patients with more than one prescription have
      more than one record. RESULTS: The longitudinal history of drug use was described
      identifying consecutive prescriptions of a specific drug, concomitant
      prescriptions of a specific drug and distinct prescriptions of a specific drug.
      Consecutive prescriptions implies that the beginning of the second prescription
      coincides with the end of the first prescription, concomitant prescriptions
      implies that the beginning of the second prescription precedes the end of the
      first prescription, distinct prescriptions implies that a gap of at least 1 day
      exists between prescriptions. Using this framework of drug representation, we
      identified episodes of drug therapy, where each episode is constituted of
      consecutive and/or concomitant prescriptions. Within each episode, prescriptions
      were categorised into theoretical phases, where the beginning of the new phase
      always coincides with the end of the previous phase. On the basis of this data
      representation, a module operating in Access and using Visual Basic for
      Applications was developed for creating episodes and phases on a routine basis
      (available from authors). A graphical representation of this conceptual model is
      presented. CONCLUSION: The development of a simple methodology for extracting and
      generating drug exposure data suitable for secondary use will allow a better
      understanding of the beneficial and adverse consequences of psychotropic drug use
      in ordinary practice.

PMID- 16893590
TI  - Promoter methylation of RASSF1A, RARbeta and DAPK predict poor prognosis of
      patients with malignant mesothelioma.
AB  - Hypermethylation occurs frequently in neoplastic cells and affects tumorigenesis.
      Malignant mesothelioma is an aggressive cancer developing in the thoracic cavity
      and patients have a rather bad prognosis. Our goal was to determine epigenetic
      alterations of a series of genes and to analyse the potential correlation of such
      changes with overall survival. We have analysed the methylation status of the
      promoter region of nine genes in serum DNA of mesothelioma patients by a nested
      methylation-specific PCR. Modest methylation frequencies were detected for APC1A
      (14.3%), RASSF1A (19.5%) and DAPK (20.0%) while hypermethylation of E-cadherin
      (71.4%) and FHIT (78.0%) occurred at a high incidence. Intermediate values were
      seen for p16(INK4a) (28.2%), APC1B (32.5%), p14(ARF) (44.2%) and RARbeta (55.8%).
      The methylation status of none of the single genes significantly influenced
      prognosis. In contrast, combining RARbeta with either DAPK or RASSF1A showed a
      significantly shorter overall survival of those patients who had both genes
      methylated compared to those with only one or no epigenetic alteration (P=0.025
      and 0.040, respectively). Similarly, the combination of all three genes revealed
      a worse prognosis for patients with double or triple methylations compared to the
      group which had only one or no gene methylated (P=0.028). Our results support the
      idea that the prognostic value of a combination of epigenetic alterations is
      superior to the impact of an individual gene alone on overall survival.

PMID- 16893591
TI  - Malignant pleural effusion, current and evolving approaches for its diagnosis and
      management.
AB  - Malignant pleural effusion is a common and debilitating complication of advanced
      malignant diseases. This problem seems to affect particularly those with lung and
      breast cancer, contributing to the poor quality of life. Approximately half of
      all patients with metastatic cancer develop a malignant pleural effusion at some
      point, which is likely to cause significant symptoms such as dyspnea and cough.
      Evacuation of the pleural fluid and prevention of its re-accumulation are the
      main goals of management. Optimal treatment is controversial and there is no
      universally standard approach. Intervention options range from observation in the
      case of asymptomatic effusions through simple thoracentesis to more invasive
      methods such as chemical and mechanical pleurodesis, pleur-X catheter drainage,
      pleuroperitoneal shunting, and pleurectomy. The best results are reported with
      thoracoscopy and talc insufflation, with an acceptable morbidity. Development of
      novel methods to control malignant pleural effusion should be a high priority in
      palliative care of cancer patients. This article reviews the current, as well as,
      novel approaches that show some promise for the future. The aim is to identify
      the proper approach for each individual patient.

PMID- 16893592
TI  - Transcriptional profiling of summer wheat, grown under different realistic UV-B
      irradiation regimes.
AB  - There is limited information on the impact of present-day ultraviolet-B (UV-B)
      radiation on a reprogramming of gene expression in crops. Summer wheat was
      cultivated in controlled environmental facilities under simulated realistic
      climatic conditions. We investigated the effect of different regimes of UV-B
      radiation on summer wheat (Triticum aestivum L.) cultivars Nandu, Star and Turbo.
      Until recently, these were most important in Bavaria. Different cultivars of
      crops often show great differences in their sensitivity towards UV-B radiation.
      To identify genes that might be involved in UV-B defence mechanisms, we first
      analyzed selected genes known to be involved in plant defence mechanisms. RNA gel
      blot analysis of RNA isolated from the flag leaf of 84-day-old plants showed
      differences in transcript levels among the cultivars. Flag leaves are known to be
      important for grain development, which was completed at 84 days post-anthesis.
      Catalase 2 (Cat2) transcripts were elevated by increased UV irradiation in all
      cultivars with highest levels in cv. Nandu. Pathogenesis-related protein 1 (PR1)
      transcripts were elevated only in cv. Star. A minor influence on transcripts for
      phenylalanine ammonia-lyase (PAL) was observed in all three cultivars. This
      indicates different levels of acclimation to UV-B radiation in the wheat
      cultivars studied. To analyze these responses in more detail, UV-B-exposed flag
      leaves of 84-day-old wheat (cv. Nandu) were pooled to isolate cDNAs of induced
      genes by suppression-subtractive hybridization (SSH). Among the initially
      isolated cDNA clones, 13 were verified by RNA gel blot analysis showing an up
      regulation at elevated levels of UV-B radiation. Functional classification
      revealed genes encoding proteins associated with protein assembly, chaperonins,
      programmed cell death and signal transduction. We also studied growth, flowering
      time, ear development and yield as more typical agricultural parameters. Plant
      growth of young plants was reduced at increased UV-B radiation. Flowering and ear
      development were delayed concomitantly, whereas total grain weight was not
      influenced at any of the UV-B irradiation regimes.

PMID- 16893593
TI  - Hand hygiene compliance in healthcare workers.
AB  - The 'clean-your-hands' campaign has now been introduced into hospitals in England
      but it was initially piloted in six acute trusts. The campaign was multi-modal
      and aimed to improve hand hygiene compliance. This review reports the findings
      from one of the trusts involved in the pilot. The campaign consisted of a toolkit
      that included placing alcohol hand rub beside patients, along with posters and
      supporting marketing materials. A guide to implementation and a strategy aimed at
      increasing patient information and empowerment was also initiated. In order to
      assess the success of the campaign, audits of hand hygiene in healthcare workers
      were conducted over a six-month period. Additionally, data were obtained from
      staff surveys, patient surveys, usage levels of alcohol hand rub and interviews
      with the on-site lead. The local campaign indicated that a multi-modal campaign
      induced a marked increase in hand hygiene compliance (from 32% to 63%), with 74%
      of staff reporting increased compliance throughout the campaign. Usage of alcohol
      hand rub increased by 184%. The majority of patients indicated that the public
      should be actively involved in helping healthcare staff to improve their hand
      hygiene.

PMID- 16893594
TI  - All change time for vaccine engineers.

PMID- 16893595
TI  - A short plate compression screw with diagonal bolts--a biomechanical evaluation
      performed experimentally and by numerical computation.
AB  - INTRODUCTION: Decreasing the length of the side plate of the dynamic hip screw
      would theoretically allow a smaller surgical incision, a shorter surgical time,
      decreased operative blood loss and minimal periosteal stripping. A new design of
      a very short plate dynamic hip screw based on two diagonal screws has been
      developed. Our study compares the new design and the four-hole side plate in
      respect to mechanical properties and bio-mechanical outcomes utilizing the Finite
      Element Analysis method. METHODS: Four pairs of fresh frozen cadaveric femora
      were extracted from male corpses aged 25-43 years (mean 34.8). One femur of each
      pair was fixated by means of the new system and the other by means of the
      conventional design. Mechanical loading was applied to all four pairs. The
      decline which occurred during the periodical loadings and the breakage loads of
      fixated bones were measured. Mechanical performance and probability of failure
      was assessed by conducting a mathematical analysis using the finite element
      method. FINDINGS: The average deflection under excessive cyclic loading was 33%
      higher in the bones fixated with the very short plate-dynamic hip screw device
      than in those fixated with the conventional dynamic hip screw. The average load
      failure during the collapse-loading test was 3120N for the very short plate
      dynamic hip screw as compared to 4160N for the regular device. Mechanical testing
      did not provide decisive results regarding failure. The mathematical analysis
      performed indicated that the maximal stress in the very short plate-dynamic hip
      screw reached values 3-4-fold higher than in the regular dynamic hip screw.
      INTERPRETATION: Although the new design offers a minimally invasive approach to
      subtrochanteric femur fracture fixation, it was found to have insufficient
      biomechanical performance resulting in high probability of mechanical failure.
      The authors believe that the finite element method may have the potential to
      serve as an additional clinical tool for performing surgical preplanning and
      assist in decision making.

PMID- 16893596
TI  - The effect of buspirone on normal and hypoarousal-driven abnormal aggression in
      rats.
AB  - Aggressiveness is associated with decreased glucocorticoid production, autonomic
      hypoarousal, and social deficits in antisocial personality disorder and its
      childhood antecedent conduct disorder. We showed previously that experimentally
      induced chronic glucocorticoid deficiency leads to abnormal forms of attack,
      autonomic hypoarousal, and social deficits in rats. We also showed that
      serotonergic neurotransmission, which downregulates aggressiveness in normal rats
      appears to lose its aggression-controlling role in glucocorticoid-deficient rats.
      We suggested that abnormal aggression develops in such rats as a consequence of
      serotonergic disturbances that result from chronic glucocorticoid deficiency.
      Here we assessed the effects of the serotonergic anxiolytic buspirone on
      aggressive behavior in normal and glucocorticoid-deficient rats. Noteworthy, this
      compound is frequently used in the clinic to control moderate aggression
      problems. As expected, buspirone dose-dependently reduced the duration of
      agonistic behaviors in normal rats exposed to resident/intruder conflicts.
      Similar to earlier experiments, glucocorticoid deficiency dramatically increased
      the share of attacks directed towards vulnerable body parts of the opponents
      (head, throat and belly). Surprisingly, 1 and 5 mg/kg buspirone dramatically
      increased the frequency of biting attacks in glucocorticoid-deficient rats. The
      share of vulnerable attacks remained as high as in vehicle-treated glucocorticoid
      deficient rats. These data show that chronic glucocorticoid deficiency disturbs
      serotonergic neurotransmission, which reverses the aggression-related effects of
      the serotonergic agent buspirone. This finding is in line with disparate human
      findings on the effects of serotonergic agents on aggression in antisocial
      personality disordered people.

PMID- 16893597
TI  - Occurrence of aflatoxin M1 in UHT milk in Turkey.
AB  - Aflatoxin M1 (AFM1) appears in milk as a direct result of the ingestion of food
      contaminated with aflatoxin B1 by cattle. The role of milk in human nutrition is
      well-known. The purpose of the study was to determine the levels of AFM1 in UHT
      milk samples in Central Anatolia, Turkey. The occurrence of AFM1 contamination in
      UHT milk samples was investigated by ELISA (Enzyme Linked Immunosorbent Assay)
      technique. A total of 129 samples of commercial UHT whole milk were analysed. The
      mean value was 108.17 ng/L. There was a high incidence rate of AFM1, with 75
      (58.1%) milk samples being contaminated. Although 68 (53%) were below the limit,
      the remaining 61 (47%) were well above the limit permitted by the EU. Four of the
      samples exceeded the prescribed limit of US regulations. It can be concluded that
      AFM1 levels in the samples purchased in Central Anatolia Region, appear to be a
      serious public health problem at the moment. Dairy farmers must be educated by
      the government authorities on potential health consequences of aflatoxins.

PMID- 16893598
TI  - Bracken-fern extracts can be clastogenic or aneugenic depending on the tissue
      cell assay.
AB  - The consumption of bracken fern (Pteridium aquilinum) as food is associated with
      a high incidence of cancer in humans and animals. We investigated the cytogenetic
      effects of bracken-fern extracts (hexane extract-HE, ethanol extract-EE, hot
      water extract-HWE and cold water extract-CWE) on chromosomes of peritoneal and
      bone-marrow cells of Swiss mice. In peritoneal cells, all four treatments (HE,
      EE, HWE and CWE) induced structural chromosome aberrations, but the EE also
      induced numerical chromosome aberrations. In bone-marrow cells both HE and CWE
      induced structural chromosome aberrations; additionally, the number of abnormal
      metaphases was higher in peritoneum than in bone marrow. We suggest that bracken
      fern induces cytogenetic damage through DNA strand breaks and affects chromosome
      segregation.

PMID- 16893599
TI  - Effect of bisphenol A, tetrachlorobisphenol A and pentachlorophenol on the
      transcriptional activities of androgen receptor-mediated reporter gene.
AB  - Previously, we developed an androgen receptor (AR)-mediated reporter gene assay
      system, and verified the antiandrogenic activity of bisphenol A (BPA) based on
      this assay. There were some similar phenol-ring structure chemicals which were
      widely used while little had been done to evaluate their effect to androgen. In
      the present study, we applied this assay to evaluate the androgenic and
      antiandrogenic activities of some phenolic chemicals including BPA,
      tetrachlorobisphenol A (TCBPA), and pentachlorophenol (PCP). The results showed
      that BPA exhibited potent antiandrogenic activity with IC50 value of 2.14 microM.
      TCBPA showed relative weaker activity with IC50 value of 10.45 microM and PCP did
      not show AR antagonistic activity. On the other hand, we failed to find AR
      agonistic effects of the three chemicals. To study the reason why BPA and TCBPA
      reduced the reporter gene expression, we increased the DHT concentration to 100
      nM and 10 microM in the reporter assay. Then, we found that the antagonist
      activity of BPA and TCBPA decreased with the increase of concentration of DHT.
      This result indicated that these two test chemicals could compete with DHT for
      the binding of AR. When comparing the structure difference between BPA, TCBPA and
      PCP, we got a preliminary founding that 3,5-substituents of phenol ring of BPA
      decrease its antiandrogenic activity. These results provide some useful
      information for the assessment of the antiandrogenic activity of BPA like
      chemicals and the potential mechanism.

PMID- 16893600
TI  - Anticipatory anxiety-induced changes in human lateral prefrontal cortex activity.
AB  - It has been suggested that frontal brain asymmetry is associated with differences
      in basic emotional dimensions, particularly in activation of systems underlying
      avoidance-withdrawal behavior. We examined regional cerebral oxygenated
      hemoglobin (O2Hb) levels in human medial prefrontal cortex (MPFC) using near
      infrared reflection spectroscopy (NIRS) prior to and during anticipatory anxiety
      to determine if NIRS could detect any anxiety-related changes. Transient anxiety
      was induced in 56 normal volunteers by anticipation and a painful shock to the
      right-hand's median nerve. Pre- and post-anxiety affective statuses were measured
      using the State-Trait Anxiety Inventory (STAI) and Temperature Character
      Inventory (TCI). NIRS recorded from the left and right frontal brain regions.
      Right MPFC O2Hb was significantly increased relative to left MPFC O2Hb during
      anticipation of the shock. Right-sided O2Hb increases were significantly
      correlated with the TCI Harm Avoidance subscale. These results support the
      hypothesis that O2Hb levels in the right frontal region correlate with anxiety or
      heightened negative affect.

PMID- 16893601
TI  - Intermittently aerated EMMC-Biobarrel (entrapped mixed microbial cell with Bio
      barrel) process for concurrent organic and nitrogen removal.
AB  - The PEMMC-Biobarrel (packed-bed of entrapped mixed microbial cells with Bio
      barrel) process and MEMMC-Biobarrel (moving EMMC-Biobarrel) process were
      investigated for enhancing concurrent organic and nitrogen removal with applied
      intermittent aeration. For the PEMMC-Biobarrel process, the EMMC-Biobarrel
      carriers were employed at a packing ratio of 20%. In the MEMMC-Biobarrel process,
      the EMMC-Biobarrel carriers with a packing ratio of 10% were added along with the
      activated sludge (AS) in the bioreactor. Three different hydraulic retention
      times (HRTs) of 9, 6 and 4 h were applied. Aeration was provided intermittently
      at time schedules of 1 h air on/1 h air off, 1 h on/1.5 h off and 1 h on/2 h off.
      Nitrogen removal in the PEMMC-Biobarrel system was not improved by increasing the
      intermittent non-aeration time period. On the other hand, the MEMMC-Biobarrel
      process enhanced nitrogen removal with increasing non-aeration time even though
      the SCOD/N(TIN) ratio decreased from 6 to 4. Significant denitrification during
      the aeration cycle was observed in the MEMMC-Biobarrel process. The MEMMC
      Biobarrel process demonstrated the most efficient organic and nitrogen removal at
      an HRT of 6 h with an intermittent aeration time schedule of 1 h on/2 h off.
      Nitrogen removal of 80% was achieved, which was about 15% higher compared to the
      AS system. TCOD and SCOD removal efficiencies were 80% and 75%, respectively.

PMID- 16893602
TI  - Steinstrasse 20 years later: Still a problem after ESWL?

PMID- 16893603
TI  - Rationale for androgens and erectile dysfunction in 2006.

PMID- 16893604
TI  - LRH-1/NR5A2 cooperates with GATA factors to regulate inhibin alpha-subunit
      promoter activity.
AB  - Inhibin alpha is the common subunit of the dimeric inhibin proteins known for
      their role in suppressing pituitary FSH secretion. In this study, we have
      examined the role of GATA factors and the nuclear receptor, LRH-1/NR5A2, in the
      regulation of inhibin alpha-subunit promoter activity. The inhibin alpha promoter
      contains two GATA-binding motifs that can be activated by GATA4 or GATA6. The
      GATA-dependence of the promoter was demonstrated by downregulating GATA
      expression in MA-10 cells using siRNA technology. We next examined whether GATA
      factors could cooperate with LRH-1, a factor recently proposed to be an important
      regulator of inhibin alpha-subunit transcription. Both GATA4 and GATA6 strongly
      synergized with LRH-1. Consistent with the cAMP-dependence of the inhibin alpha
      subunit promoter, GATA/LRH-1 synergism was markedly enhanced by PKA and the co
      activator protein CBP. Thus, our results identify LRH-1 as a new transcriptional
      partner for GATA factors in the regulation of inhibin alpha-subunit gene
      expression.

PMID- 16893605
TI  - Observations of Si field evaporation.
AB  - Field evaporation studies of crystalline <100> Si were performed in a three
      dimensional atom-probe, which utilized a local electrode geometry. Several
      distinct phenomena were observed. Si field evaporation rates showed: (1) no
      measurable dependence on temperature below 110K, (2) an exponential dependence on
      evaporation rate as a function of temperature above 110K, and (3) no dependence
      on substrate doping (i.e., electrical conductivity) as high as 10 Omega cm in the
      temperature range of 40-150K. Two distinct evaporation modes were observed. The
      first was associated with approximately 1at% H+ in the mass spectrum. Negligible
      amounts of H were detected in the mass spectra of the second mode. When the pulse
      fraction (pf) was increased from 5% to 30%, the presence of H+ in the mass
      spectra, i.e. operation in the first mode, was associated with a degradation in
      mass resolution by as much as 80% for the 10 Omega cm Si samples. Conversely, no
      loss in mass resolution was detected for the approximately 0.001 Omega cm samples
      over the pf range studied.

PMID- 16893606
TI  - If control of Neospora caninum infection is technically feasible does it make
      economic sense?
AB  - Recent work on Neospora caninum, a protozoan parasite that causes abortions in
      dairy cattle has focused on a number of different control options. Modelling has
      suggested the most effective options for control but the present paper argues
      that the most effective option might not necessarily be optimal from an economic
      point of view. Decision trees, using published quantitative data, were
      constructed to choose between four different control strategies. The costs of
      these interventions, such as 'test and cull', therapeutic treatment with a
      pharmaceutical, vaccination or "doing nothing" were compared, and modelled, in
      the first instance, on the New Zealand and Australian dairy situation. It is
      argued however, that the relative costs in other countries might be similar and
      that only the availability of a registered vaccine will change the decision tree
      outcomes, as does the within-herd prevalence of N. caninum infection. To "do
      nothing" emerged as the optimal economic choice for N. caninum
      infections/abortions up to a within-herd prevalence of 18%, when viewed over a 1
      year horizon, or 21% when costs were calculated over a 5 years horizon. For a
      higher (>or=21%) within-herd prevalence of N. caninum infection vaccination
      provided the best (i.e. most economic) strategy. Despite being the most
      efficacious solutions, 'test and cull' or therapeutic treatment never provided a
      viable economic alternative to vaccination or "doing nothing". Decision tree
      analysis thus provided clear outcomes in terms of economically optimal
      strategies. The same approach is likely to be applicable to other countries and
      the beef industry, with only minor changes expected in the relationships of
      decisions versus within-herd prevalence of N. caninum infection.

PMID- 16893607
TI  - Partial thickness burns caused by a spontaneously exploding mobile phone.

PMID- 16893608
TI  - Bouncy castle burns.

PMID- 16893609
TI  - An antisense oligodeoxynucleotide to the mu opioid receptor attenuates cocaine
      induced behavioral sensitization and reward in mice.
AB  - Numerous studies support a role for the endogenous opioid system in cocaine
      influenced behavior. Few of these studies, however, selectively delineate a role
      for the mu opioid receptor (MOR) in this regard. This investigation examined if
      the MOR modulates cocaine-induced behavior in mice using a 17-base antisense
      oligodeoxynucleotide (AS ODN) directed against the MOR coding sequence 16-32.
      Specifically, cocaine-induced behavioral sensitization and conditioned reward
      were investigated. For the sensitization study, C57BL/6J mice received eight
      intermittent i.c.v. infusions of saline, mismatch oligodeoxynucleotide (ODN) (20
      microg/4 microl) or AS ODN (20 microg/4 microl) over 20 days. Mice also received
      concomitant once daily i.p. injections of saline (4 ml/kg) or cocaine (15 mg/kg)
      for 10 days. There was a 7-day withdrawal period, after which all mice were
      challenged with cocaine (15 mg/kg) to test for behavioral sensitization. For the
      conditioned place preference (CPP) study, mice received five i.c.v. infusions of
      mismatch ODN or MOR AS ODN (days 1-5). An unbiased counterbalanced conditioning
      procedure was used where mice were conditioned with saline (4 ml/kg, i.p.) and
      cocaine (15 mg/kg, i.p.) on alternate days for four sessions (days 3-6). Mice
      were tested on day 7 for CPP. Immediately following testing, [3H]DAMGO (D-Ala2, N
      Me-Phe4, Gly-ol5-enkephalin) receptor binding to brain homogenates was conducted.
      MOR AS attenuated cocaine-induced behavioral sensitization and conditioned
      reward. MOR AS ODN also reduced [3H]DAMGO binding. Collectively, these findings
      implicate the MOR as playing an important neuromodulatory role in the behavioral
      effects of cocaine in mice.

PMID- 16893610
TI  - Serotonin-induced in vitro long-term facilitation exhibits differential pattern
      sensitivity in cervical and thoracic inspiratory motor output.
AB  - Intermittent hypoxia induces 5-HT-dependent, pattern-sensitive long-term
      facilitation (LTF) of spinal respiratory motor output. We used a split-bath in
      vitro neonatal rat brainstem-spinal cord preparation to test whether: 1)
      intermittent spinal 5-HT exposure (without hypoxia) is sufficient to induce LTF
      in phrenic and intercostal inspiratory motor outputs; 2) LTF magnitude is greater
      in intercostal versus phrenic activity; and 3) phrenic and intercostal motor
      output exhibits differential pattern sensitivity to 5-HT application. With a
      barrier at spinal segment C1, 5-HT (5 muM) was applied episodically (3 min 5-HT,
      5 min wash, x3) to the spinal cord (C2-L1) while recording inspiratory bursts in
      cervical (C4 or C5) and thoracic (T5 or T6) ventral roots. Episodic 5-HT
      application increased cervical and thoracic burst amplitudes to 136+/-22% and
      150+/-22% of baseline, respectively, at 120 min post-drug (P<0.01). Continuous 5
      HT application (5 muM, 9 min) had no effect on cervical burst amplitude at 120
      min post-drug, but increased thoracic burst amplitude to 142+/-11% of baseline at
      120 min post-drug (P<0.001). Methysergide pretreatment abolished both cervical
      and thoracic 5-HT-induced LTF. Quantitative reverse transcriptase-polymerase
      chain reaction and immunocytochemistry revealed that 5-HT(2A) and 5-HT(7)
      receptor subtypes (receptors known to influence LTF expression in adult rats) are
      expressed in ventral cervical and thoracic spinal cord with no differences in
      expression levels due to spinal segment or age. Thus, 5-HT is sufficient to
      induce spinal LTF in neonatal rats and differences in pattern sensitivity suggest
      heterogeneity in underlying mechanisms.

PMID- 16893611
TI  - Deal in the womb: fetal opiates, parent-offspring conflict, and the future of
      midwifery.
AB  - This paper argues that parent-offspring conflict is mediated by placental beta
      endorphins in placental mammals, i.e., foetuses make their mothers endorphin
      dependent then manipulate them to increase nutrient allocation to the placenta.
      This hypothesis predicts that: (1) anatomic position of endorphin production
      should mirror its presumed role in fetal-maternal conflict; (2) endorphin levels
      should co-vary positively with nutrient carrying capacity of maternal blood
      system; (3) postpartum psychological symptoms (postpartum blues, depression and
      psychosis) in humans are side-effects of this mechanism that can be interpreted
      as endorphin-deprivation symptoms; (4) shortly after parturition, placentophagia
      could play an adaptive role in decreasing the negative side-effects of fetal
      manipulation; (5) later, breast-feeding induced endorphin excretion of the
      maternal pituitary saves mother from further deprivation symptoms. Finally,
      whatever the molecular mechanism of fetal manipulation is, widespread and intense
      medical care (such as caesarean section and use of antidepressants) affects the
      present and future evolution of mother-foetus conflict in the human species (and
      also in domestic animals) to increase 'fetal aggressiveness' and thus technology
      dependency of reproduction.

PMID- 16893612
TI  - AIDS: caused by development of resistance to drugs in a non-target intracellular
      parasite.
AB  - The origin of acquired immune disorder syndrome (AIDS) has been the subject of
      substantial controversy both in the scientific community and in the popular
      press. The debate involves the mode of transmission of a simian virus (SIV) to
      humans. Both major camps in the argument presume that humans are normally free of
      such viruses and assume that once the simian virus was transmitted, it
      immediately infected some T-cells and caused the release of toxic agents that
      killed off bystander (uninfected) T-cells resulting in AIDS. The evolution of the
      Simian virus (SIV) into a human virus (HIV) is regarded as an artifact. In
      contrast, a fundamentally different hypothesis has been proposed [Parris GE. Med
      Hypotheses 2004;62(3):354-7] in which it is presumed that in hyper-endemic areas
      of malaria (central Africa), all primates (humans and non-human primates) have
      shared a retrovirus that augments their T-cell response to the malaria parasite.
      The virus can be called "primate T-cell retrovirus" (PTRV). Over thousands of
      years the virus has crossed species lines many times (with little effect) and
      typically adapts to the host quickly. In this model, AIDS is seen to be the
      result of the development of resistance of the virus (PTRV) to continuous
      exposure to pro-apoptotic (schizonticidal) aminoquinoline drugs used to prevent
      malaria. The hypothesis was originally proposed based on biochemical activities
      of the aminoquinolines (e.g., pamaquine (plasmoquine(TM)), primaquine and
      chloroquine), but recent publications demonstrated that some of these drugs
      definitely adversely affect HIV and other viruses and logically would cause them
      to evolve resistance. Review of the timeline that has been created for the
      evolution of HIV in humans is also shown to be qualitatively and quantitatively
      consistent with this hypothesis (and not with either version of the conventional
      hypothesis). SARS and Ebola also fit this pattern.

PMID- 16893613
TI  - Co-administration of ramelton and fluvoxamine to increase levels of interleukin
      2.
AB  - Ramelton is a medication recently approved by the FDA for treatment of insomnia.
      Ramelton is an analogue of melatonin with a higher affinity even than that of the
      natural ligand. Clinically this potentially strong effect of the ligand is
      blunted by the fact that upon oral ingestion there is first pass metabolism of
      greater than 95%. This liver metabolism is mediated by the CYP1A2 enzyme. It
      turns out that the medication fluvoxamine approved by the FDA for the treatment
      of obsessive compulsive disorder is a potent inhibitor of the CYP1A2 enzyme, with
      the effect that co-administration of ramelton and fluvoxamine increases blood
      levels of ramelton by 100-200 fold. It turns out that lymphocytes bear the
      melatnonin receptors and stimulation of these receptors on lymphocytes cause the
      lymphocytes to elaborate the pro-inflammatory cytokine interleukin-2 (Il-2).
      Thus, here we point out that co-administration of ramelton and modest doses of
      fluvoxamine may be able to smoothly produce increased levels of Il-2, this may be
      useful in diseases and conditions such as metastatic cancer and maintenance of
      suppression of the HIV virus.

PMID- 16893614
TI  - 7-Hydroxystaurosporine may have a therapeutic role in treatment-resistant
      depression by inhibition of calcium/calmodulin-dependent protein kinase II.

PMID- 16893615
TI  - Deviations from Chargaff's second parity rule in organellar DNA Insights into the
      evolution of organellar genomes.
AB  - Chargaff' s second parity rule (PR2) states that complementary nucleotides are
      met with almost equal frequencies in single stranded DNA. This is indeed the case
      for all bacterial and eukaryotic genomes studied, although the genomic patterns
      may differ among genomes in terms of local deviations. The behaviour of
      organellar genomes regarding the second parity rule has not been studied in
      detail up to now. We tested all available organellar genomes and found that a
      large number of mitochondrial genomes significantly deviate from the 2nd parity
      rule in contrast to the eubacterial ones, although mitochondria are believed to
      have evolved from proteobacteria. Moreover, mitochondria may be divided into
      three distinct sub-groups according to their overall deviation from the
      aforementioned parity rule. On the other hand, chloroplast genomes share the
      pattern of eubacterial genomes and, interestingly, so do mitochondrial genomes
      originating from plants and some fungi. The deviation from the second parity is
      found to be weakly correlated with the overall excess of purines against
      pyrimidines. The behaviour of the large majority of the mitochondrial genomes may
      be attributed to their distinct mode of replication, which is fundamentally
      different from the one of the eubacteria. Differences between chloroplast and
      mitochondrial genomes might also be explained on the basis of different
      replication mechanisms and correlated to differences in the genome size and
      compaction. The results presented herein may provide some insight into different
      modes of evolution of genome structure between chloroplasts and mitochondria.

PMID- 16893617
TI  - Dephosphorylation of ribosomal protein P0 in response to troglitazone-induced
      cytotoxicity.
AB  - Troglitazone (TRO)-induced cytotoxicity was investigated in HepG2 cells. The
      cells were exposed to TRO as well as rosiglitazone (RSG) at concentrations of 0,
      25, 50 and 75 microM for 48 h. Total proteins were separated by two-dimensional
      electrophoresis and visualized by silver staining. We focused on a protein spot
      at an approximate molecular weight of 35 kDa and isoelectric point (pI) of 5.7,
      which appeared only with the cytotoxic concentrations (50 and 75 microM) of TRO,
      but not with the low concentration (25 microM) of TRO or any concentrations of
      RSG. This protein spot was subjected to amino acid sequence analysis and
      identified as ribosomal protein P0 (P0). Interestingly, without any significant
      induction of its protein and mRNA, P0 was dephosphorylated depending on the
      concentration- and time-dependent manner of TRO-induced cytotoxicity.
      Pretreatment with a general caspase inhibitor, Z-VAD.fmk, prevented cleavage of
      caspase-3 but demonstrated a slight improvement of cytotoxicity induced by TRO.
      Thus, these effects could not prevent the dephosphorylation of P0. Our results
      strongly suggest that a post-translational modification, dephosphorylation, of P0
      is associated with TRO-induced cytotoxicity.

PMID- 16893616
TI  - Chlamydophila psittaci in free-living Blue-fronted Amazon parrots (Amazona
      aestiva) and Hyacinth macaws (Anodorhynchus hyacinthinus) in the Pantanal of Mato
      Grosso do Sul, Brazil.
AB  - Chlamydophila psittaci (C. psittaci) infection was evaluated in 77 free-living
      nestlings of Blue-fronted Amazon parrots (Amazona aestiva) and Hyacinth macaws
      (Anodorhynchus hyacinthinus) in the Pantanal of Mato Grosso do Sul, Brazil.
      Tracheal and cloacal swab samples from 32 wild parrot and 45 macaw nestlings were
      submitted to semi-nested PCR, while serum samples were submitted to complement
      fixation test (CFT). Although all 32 Amazon parrot serum samples were negative by
      CFT, cloacal swabs from two birds were positive for Chlamydophila DNA by semi
      nested PCR (6.3%); these positive birds were 32 and 45 days old. In macaws,
      tracheal and cloacal swabs were positive in 8.9% and 26.7% of the samples,
      respectively. Complement-fixing antibodies were detected in 4.8% of the macaw
      nestlings; macaw nestlings with positive findings were between 33 and 88 days
      old. These results indicate widespread dissemination of this pathogen in the two
      evaluated psittacine populations. No birds had clinical signs suggestive of
      chlamydiosis. To the best of our knowledge, this is the first report on C.
      psittaci in free-living Blue-fronted Amazon parrots and Hyacinth macaws in
      Brazil.

PMID- 16893618
TI  - Octylphenol induces apoptosis in cultured rat Sertoli cells.
AB  - In this study, the effects of 4-tert-octylphenol (OP) were examined on the
      viability of rat cultured Sertoli cells using the MTT assay and OP-induced
      apoptosis was detected by transmission electron microscope (TEM), flow cytometric
      analysis and Hoechst staining. In addition, RT-PCR was used to analyze the levels
      of Bcl-2 and Bax mRNA. Bcl-2, Bax and caspase-3 protein expressions were
      determined by Western blot analysis. Sertoli cells were treated with OP from 30
      to 60microM for 6-24h. Decreased viability of Sertoli cells and increased
      apoptosis occurred in a concentration- and a time-dependent manner. The
      expression of Bcl-2 was down-regulated, while the expression of Bax up-regulated.
      OP also down-regulated the expression of 32kDa procaspase-3, which was cleaved to
      generate active subunit (17kDa). These results suggest that OP may induce Sertoli
      cell apoptosis by regulation of Bcl-2/Bax and caspase-3 activation.

PMID- 16893619
TI  - Microencapsulation of drugs by electro-hydro-dynamic atomization.
AB  - This paper presents practical aspects of production of polymeric particles loaded
      with a drug by electro-hydro-dynamic atomization (EHDA). Particles were produced
      from paracetamol (4-acetamidophenol), budesonide and polylactic acid containing
      Taxol (paclitaxel). Influence of solvent type and evaporation rate, as well as
      other polymers additives on particle morphology and drug release rate is
      demonstrated. It is shown that quickly evaporating solvents have a tendency to
      form hollow particles. Drug release rate from hollow particles is substantially
      higher than from solid ones. Addition of water-soluble polymer, polyethylene
      glycol, also increases drug release rate.

PMID- 16893621
TI  - Concepts and possibilities in forensic intelligence.
AB  - Forensic intelligence can be viewed as comprising two parts, one directly
      concerning intelligence delivery in forensic casework, the other considering
      performance aspects of forensic work, loosely termed here as business
      intelligence. Forensic casework can be viewed as processes that produce an
      intelligence product useful to police investigations. Traditionally, forensic
      intelligence production has been confined to discipline-specific activity. This
      paper examines the concepts, processes and intelligence products delivered in
      forensic casework, the information repositories available from forensic
      examinations, and ways to produce within- and across-discipline casework
      correlations by using information technology to capitalise on the information
      sets available. Such analysis presents opportunities to improve forensic
      intelligence services as well as challenges for technical solutions to deliver
      appropriate data-mining capabilities for available information sets, such as
      digital photographs. Business intelligence refers primarily to examination of
      efficiency and effectiveness of forensic service delivery. This paper discusses
      measures of forensic activity and their relationship to crime outcomes as a
      measure of forensic effectiveness.

PMID- 16893620
TI  - Reconstruction of the inventory of materia medica used by members of the Jewish
      community of medieval Cairo according to prescriptions found in the Taylor
      Schechter Genizah collection, Cambridge.
AB  - The Taylor-Schechter (T-S) collection at Cambridge University Library is the
      biggest of all Cairo Genizah collections in the world. The importance and the
      potential of research into the medical aspects of the Genizah documents were
      clear to researcher since the early 1960s. A few works have been published since,
      usually focusing on one subject, or even important single manuscripts. The
      current research concerned mainly with one aspect of the history of medicine of
      the Jewish community of Cairo (as a reflection of Eastern medieval societies),
      namely the practical uses of natural substances for medicine. The most
      interesting and original information is undoubtedly to be found in the 141
      prescriptions, as they reflect the medical reality that actually existed. And
      indeed, 242 substances were recorded in the prescriptions identified: 195
      substances of plants origin (80.6%), 27 inorganic materials (11.2%) and 20
      substances of animal origin (8.2%) were recorded as being in practical used for
      medicinal purposes. The most frequently mentioned substances were the rose,
      myrobalan, sugar, almonds, and endive. The most prevalent ailments: eye diseases,
      headache, constipations (purgative), cough, skin diseases, stomach, fever,
      gynaecological problems, haemorrhoids, liver ailments, lice, swellings, dental
      trouble, ulcers, and problems of the urinary tract.

PMID- 16893622
TI  - Histological and biological developmental characterization of the human
      cerebellar cortex.
AB  - The aim of this study was to investigate the histological and biological features
      of the human cerebellar cortex development and differentiation. We analyzed 52
      brains of fetal and infant death victims, aged from 17 gestational weeks to 12th
      postnatal month. In particular, in the cerebellar cortex at different ages we
      evaluated, besides the structural aspects, the expression of several biomarkers
      implicated in proliferative processes (c-fos, PCNA and apoptosis). We observed
      morphological patterns progressively evolving every month, from the indefinite
      structure of the second gestational trimester to the four-layered structure
      (external granular layer, molecular layer, Purkinje cell layer, internal granular
      layer) of the late fetal cortex and subsequently to the three-layered postnatal
      definitive morphology, due to involution of the external granular layer. The
      evaluation of the biological features of the cerebellar cortex showed high
      proliferative activity mainly confined to the transient external granular layer
      in prenatal life, and high apoptotic index after birth. Thus, the histological
      examination, better with the support of biomarker investigations, allows with
      accuracy to describe the dynamic sequence of steps that occur in human cerebellar
      cortex development and to establish in each case the age, namely the pre- or
      postnatal month of life. Consequently, we can diagnose delayed or altered
      processes of differentiation during the development of the human cerebellar
      cortex.

PMID- 16893624
TI  - Real-time PCR using hybridization probes for the rapid and specific
      identification of Francisella tularensis subspecies tularensis.
AB  - Tularemia is a plague-like infection caused by Francisella (F.) tularensis
      classified as a biological warfare agent. F. tularensis subsp. tularensis is the
      most virulent subspecies demanding rapid diagnosis. Typing systems for this
      fastidious bacterium to the subspecies level are laborious and time consuming.
      Therefore, the aim of this study was to develop a real-time PCR for the rapid and
      specific identification of F. tularensis subsp. tularensis. The specificity of
      the assay was determined using a comprehensive panel of Francisella strains,
      clinically relevant bacteria, and DNA preparations of potential hosts. F.
      tularensis subsp. tularensis was specifically detected but no other organisms.
      The range of linearity was determined to be 100 fg to 10 ng, the lower limit of
      detection was 25 fg of DNA (13 genome equivalents). An internal amplification
      control PCR system targeting lambda phage DNA was included. Neither the internal
      amplification control nor host DNA influenced the cycle threshold values obtained
      for F. tularensis subsp. tularensis. In conclusion, we have developed a highly
      sensitive and specific assay that can be integrated into real-time PCR-based
      identification procedures for biological agents. This is a major diagnostic
      improvement, as all other methods for the specific identification of F.
      tularensis subsp. tularensis are more time consuming.

PMID- 16893623
TI  - Cognitive correlates of HVOT performance differ between individuals with mild
      cognitive impairment and normal controls.
AB  - OBJECTIVE: To clinically characterize performance on the Hooper Visual
      Organization Test (HVOT) among participants with mild cognitive impairment (MCI)
      and to identify naming and executive functioning correlates associated with HVOT
      performance among MCI participants and normal controls (NC). BACKGROUND: The HVOT
      is a common neuropsychological instrument that measures visuospatial skills and
      agnosia. It has, however, been criticized for its multifactorial nature, as
      several studies have reported executive or language correlates of HVOT
      performance. To our knowledge, simultaneous comparison of executive functioning
      and language demands of the HVOT has never been performed among an older cohort.
      METHODS: The HVOT, two tests of executive functioning [Trail Making Test, Part B
      (TMT-B), Controlled Oral Word Association (COWA)] and two tests of naming
      [abbreviated Boston Naming Test (BNT), Animal Naming] were administered to 222
      NC, 166 MCI, and 68 Alzheimer's disease (AD) individuals. RESULTS: HVOT scores
      were significantly different between all three groups in the expected direction
      (AD<MCI<NC). Linear regression among NC participants revealed that COWA, age, and
      BNT were significantly associated with HVOT scores, accounting for 12%, 6%, and
      4% of HVOT variance, respectively. Among MCI participants, the BNT accounted for
      43% of HVOT variance. Neither TMT-B nor Animal Naming was a significant predictor
      for either group. CONCLUSION: Among NC participants, rapid word generation (i.e.,
      COWA), a measure of executive functioning, is the most salient predictor of HVOT
      performance. In contrast, lexical retrieval (i.e., BNT) is the most salient
      language or executive functioning predictor of HVOT performance among MCI
      participants. These findings extend previous claims that the HVOT is
      multifactorial by suggesting that reduced HVOT performance in MCI patients may be
      related to mild lexical retrieval impairments.

PMID- 16893625
TI  - Development of quantitative real-time PCR assays to detect Rickettsia typhi and
      Rickettsia felis, the causative agents of murine typhus and flea-borne spotted
      fever.
AB  - Rickettsia typhi and Rickettsia felis are the etiologic agents of murine typhus
      and flea-borne spotted fever, respectively. We have constructed two quantitative
      real-time polymerase chain reaction (qPCR) assays to detect these pathogenic
      rickettsiae. The qPCR assays were developed utilizing unique sequences of the R.
      typhi and R. felis outer membrane protein B genes (ompB) to design the specific
      primers and molecular beacon probes. The assays were found to be species-specific
      and did not yield false-positive reactions with nucleic acid from other
      rickettsiae, orientiae, neorickettsiae or unrelated bacteria. In addition, the
      assays were sensitive enough to detect three target sequence copies per reaction
      and were capable of detecting R. typhi and R. felis nucleic acid in the cat flea,
      Ctenocephalides felis. These results demonstrate that two sensitive and specific
      qPCR assays have been successfully developed to detect and enumerate R. typhi and
      R. felis.

PMID- 16893626
TI  - A competitive neural model of small number detection.
AB  - The ability to represent numbers is a key attribute for both humans and animals.
      Recent developments in the understanding of numerical processing has led to the
      proposal that humans utilise two independent representations of number, one for
      real numbers and another for integers. We describe a computational model of small
      number detection to explore the relationship between these core systems of
      number. We use a combination of unsupervised and supervised neural networks to
      simulate the interaction between the real and integer representations. For real
      values we use a self-organised spatial representation of number. For integer
      values we use a supervised network motivated by linguistic processing. During
      training and testing, the networks exhibit behavioural characteristics such as
      the number size and numerical distance effects. Each representation is combined
      using the mixture-of-experts architecture that allows us to model the
      subitization limit (the maximum number of visual stimuli that can be accurately
      quantified almost immediately) as the competitive allocation of representations
      for number detection, where the crossover point between deploying the real and
      integer representations of number is obtained through a process of learning. Our
      results suggest that the existence of two core systems of number is at least
      computationally plausible and further suggests that the subitization limit
      emerges through the interaction of spatial and linguistic numerical processing.
      This provides computational evidence for one way in which small and large numbers
      are related in humans.

PMID- 16893627
TI  - Dravet syndrome: a study of 53 patients.
AB  - OBJECTIVE: We analyzed the electroclinical features, treatment and evolution of
      patients with Dravet syndrome (DS). MATERIAL AND METHODS: We evaluated the
      clinical records of 53 patients that met the diagnostic criteria of DS according
      to the ILAE classification of 1989 seen at our center between February 1990 and
      December 2004. RESULTS: Thirty-four male and 19 female patients met the
      diagnostic criteria of DS. Mean time of follow-up was 10 years. The mean age at
      onset was 6 months and in all patients the seizures were associated with febrile
      illness. Myoclonias were found in 39 children. These seizures appeared between
      the ages of 1 and 5.5 years, with an average of 1 year and 5 months. The seizures
      were difficult to control with AEDs. All patients presented some degree of mental
      delay. At the age of 6 years, one of the children in our series presented
      kinesigenic paroxysmal dyskinesias. Twenty patients were placed on the ketogenic
      diet (KD). Two did not tolerate the KD and the diet was ineffective in five
      cases. The other 13 showed different degrees of control of seizures. CONCLUSION:
      The present study confirms the severity and intractability of the seizures and
      the difficulties to make an early diagnosis in DS. The onset of febrile seizures
      or seizures related to infectious disease or vaccination, focal or generalized,
      prolonged in time and during the first year of life, is especially suggestive of
      DS. The final diagnosis is usually made after 2 or 3 years when the
      electroclinical picture is complete, but earlier diagnosis is desirable.
      Myoclonias are the most representative type of non-febrile seizures in this
      syndrome but are not always present. Cognitive development is poor in all
      patients. Treatment with the KD should be considered early. A ion-channel
      disorder could explain the association between DS and paroxysmal diskinesias, as
      seen in one of our patients.

PMID- 16893629
TI  - Experiments I'll never forget: using NMR to watch beta-lactamase working, and
      using microtitre trays for minimum inhibitory concentration determination.

PMID- 16893628
TI  - Morphology of the paracingulate sulcus and executive cognition in schizophrenia.
AB  - Previous studies have shown that schizophrenia patients display a left
      lateralized reduction in cortical folding of the paracingulate cortex, although
      the functional significance of this anomaly is unclear. We examined the influence
      of paracingulate sulcus (PCS) asymmetries on cognitive performance in 37 male
      schizophrenia patients and 43 male controls. Across both groups, a leftward PCS
      asymmetry was associated with better spatial working memory performance than
      either a rightward asymmetric or symmetric folding pattern. This suggests that
      prior reports of impaired performance on such tasks in schizophrenia may be
      partly explained by the reduced frequency of a leftward PCS asymmetry in this
      population.

PMID- 16893630
TI  - Physicochemical properties of low molecular weight alkylated chitosans: a new
      class of potential nonviral vectors for gene delivery.
AB  - Low molecular weight chitosans grafted with N-/2(3)-(dodec-2-enyl)succinoyl
      groups (HM-LMW-chitosans) with a mean molecular mass of 5 kDa, a degree of
      acetylation of 3% and a degree of tetradecenoyl substitution (TDC) of 3-18 mol%
      have been synthesized. These molecules are monodisperse and soluble in water at
      neutral pH. Using tensiometry and Nile Red fluorescence, the HM-LMW-chitosans
      were found to form micelles through hydrophobic interactions involving their
      tetradecenoyl chains and nonprotonated glucosamine monomers. Their critical
      micelle concentration decreases with increasing TDC values but varies little with
      pH and salt. Interaction with large unilamellar vesicles taken as model membranes
      indicated that HM-LMW-chitosans interact mainly with vesicles mimicking the inner
      leaflet of biomembranes both through electrostatic and hydrophobic interactions.
      This preferential interaction may destabilize endosomal membranes and favor the
      DNA release into the cytoplasm in gene delivery applications. Moreover, since
      this interaction significantly decreased the membrane fluidity of these vesicles,
      the HM-LMC-chitosans are thought to exhibit limited lateral mobility and flip
      flop ability, and thus, limited cytotoxicity. These properties suggest that the
      HM-LMW-chitosans may constitute a promising new class of nonviral vectors for
      gene therapy.

PMID- 16893631
TI  - Sperm fatty acid composition in subfertile men.
AB  - INTRODUCTION: The lipid composition of spermatozoa plays an important role for
      successful fertilization. PATIENTS AND METHODS: In the present study, we analyzed
      the fatty acid (FA) composition of spermatozoa of normozoospermic,
      asthenozoospermic, oligozoospermic and oligoasthenozoospermic men. RESULTS:
      Spermatozoa from asthenozoospermic (P<0.01), oligozoospermic (P<0.05) and
      oligoasthenozoospermic men (P<0.05) had lower levels of docosahexaenoic acid
      (22:6w3, DHA) than those from normozoospermic men. In oligozoospermic and
      asthenozoospermic men, spermatozoa 18:0 content was higher than that of
      normozoospermics (P<0.01 and P<0.001, respectively). 18:1w9 was higher in
      oligoasthenozoospermic and oligozoospermic samples when compared with
      normozoospermic samples (P<0.05 for both). While from the point of view of total
      w6 FAs there was no significant difference among the groups, the w6/w3 ratio was
      significantly higher in asthenozoospermic samples than in normozoospermic samples
      (P<0.05). Monounsaturated fatty acids (MFA) were higher in oligozoospermic
      samples (P<0.05) than in normozoospermic samples, polyunsaturated fatty acids
      (PUFA) were lower in asthenozoospermic (P<0.01), oligoasthenozoospermic (P<0.05)
      and oligozoospermic samples (P<0.05) than in normozoospermic samples. Saturated
      fatty acids (SFA) were significantly higher in asthenozoospermic (P<0.01) and
      oligozoospermic samples (P<0.05) compared with normozoospermic samples. In
      correlation analysis, there were significant positive correlations between DHA
      with sperm motility (r=0.53), sperm concentration (r=0.36) and normal sperm
      morphology (r=0.30). In addition, there were significant correlations between
      PUFA with sperm motility (r=0.50), sperm concentration (r=0.35), and normal sperm
      morphology (r=0.28), and between w6/w3 with sperm motility (r=-0.47), sperm
      concentration (r=-0.27), and normal sperm morphology(r=-0.24). DISCUSSION: These
      suggest that decreased DHA and PUFA, and increased w6/w3 in spermatozoa may be
      related to infertility in oligo- and/or asthenozoospermic men.

PMID- 16893632
TI  - Donor selection for unrelated cord blood transplants.
AB  - The number of unrelated cord blood transplants is increasing, with more than 8000
      patients reported worldwide. Criteria of donor choice have been identified. Cell
      dose measured by number of nucleated cells is the most important factor, thus
      increases in cell dose can partially overcome the presence of HLA
      incompatibilities. Overall, increasing the number of HLA incompatibilities is
      associated with non-engraftment, but it also decreases the risk of relapse in
      patients with malignant disease, resulting in an absence of effect of HLA
      incompatibilities on event-free survival (survival without relapse or
      complications related to the transplant). However, in patients with non-malignant
      disorders, increasing the number of HLA incompatibilities decreases the overall
      survival. These results show that criteria of donor choice based on number of
      infused cells, number of HLA incompatibilities and diagnosis improve outcomes of
      unrelated cord blood transplants. Currently, owing to the possibility of using a
      non HLA identical donor, most patients can find a donor, increasing the need for
      the development of the inventory of cord blood banks. Methods of improving
      engraftment are currently under investigation.

PMID- 16893634
TI  - Modern immunogenetics: simple questions with complex answers.

PMID- 16893635
TI  - Transplantation recent advances in transplantation immunology.

PMID- 16893636
TI  - Response to copper stress in aposymbiotically grown lichen mycobiont Cladonia
      cristatella: uptake, viability, ergosterol and production of non-protein thiols.
AB  - The mycobiont of lichens usually determines the morphology of the symbiotic
      organism and is also dominates in terms of biomass. However, its role for
      sensitivity or tolerance of lichens to heavy metals is almost unknown. In the
      present study, the influence of copper (Cu) on the aposymbiotically-grown
      mycobiont of Cladonia cristatella was assessed. Intracellular Cu uptake was
      correlated with increasing Cu concentrations over a 24-h exposure time.
      Viability, measured as the degree of reduction of triphenyltetrazolium chloride
      to triphenyl formazan, as well as to ergosterol levels, decreased with growing Cu
      concentrations tested. Reduced glutathione (GSH) was found to be the most
      abundant low-molecular-weight thiol in the hyphae of C. cristatella and its
      intracellular content increased at concentrations of 10mum Cu. Higher Cu
      concentrations caused a significant decrease in GSH, possibly due to heavy metal
      induced oxidation of GSH to glutathione disulphide (GSSG). Free cysteine levels
      were relatively constant. As expected, we did not observe the production of
      phytochelatins in the mycobiont, contrary to what is found in intact lichens and
      axenic cultures of their photobionts.

PMID- 16893637
TI  - Autofluorescence detection of arbuscular mycorrhizal fungal structures in palm
      roots: an underestimated experimental method.
AB  - The aim of this study was to reassess the use of autofluorescence for evaluating
      AM colonization in mycorrhizal roots in the light of criticisms of this method
      that affirmed that only metabolically inactive arbuscules autofluoresce. It was
      also investigated whether other mycorrhizal structures, such as hyphae, vesicles
      and spores, could be detected by autofluorescence, and whether the
      autofluorescence pattern of AM fungal structures could be exploited
      methodologically, for example, in the detection and sorting of spores by flow
      cytometry. Mycorrhizal roots of the palm species Brahea armata, Chamaerops
      humilis, Phoenix canariensis and Phoenix dactylifera were sectioned and observed
      by means of fluorescence microscopy. In addition, fungal structures isolated from
      mycorrhizal roots of P. dactylifera were examined. The same root sections and
      isolated fungal structures were subjected to vital staining with nitro blue
      tetrazolium to determine their metabolic state (active or inactive). Moreover,
      spores of Glomus intraradices, and Glomus clarum were studied by epifluorescence
      and flow cytometry. Mycorrhizal whole roots of Medicago sativa were also assessed
      by autofluorescence detection. In contrast to previous reports, the results
      presented in this paper clearly demonstrate that all fungal structures, both
      intra- and extraradical, autofluoresced under blue light excitation, regardless
      of their state (dead or alive). Some arbuscules isolated from roots and mature
      spores showed further autofluorescence under green light excitation. The source
      of the autofluorescence was localized in the fungal cell wall. It was shown that
      AM spores can be detected by flow cytometry. The results support the use of
      autofluorescence for the evaluation of AM colonization, at least in palm species,
      and refute previous criticisms of the method.

PMID- 16893638
TI  - Respiratory symptoms/diseases and environmental tobacco smoke (ETS) in never
      smoker Italian women.
AB  - AIM: To study the relationship between respiratory/allergic disorders and chronic
      environmental tobacco smoke (ETS) exposure to husband or at workplace among non
      smoking women of a general population in Italy. METHODS: Analyses regard 2195
      married or employed women. Information was collected through a self-administered
      questionnaire. ETS exposure was validated by salivary cotinine. RESULTS: Exposure
      both to husband and at work resulted a significant risk factor for current
      dyspnoea (odds ratio (OR) 1.61, 95% confidence interval (CI) 1.20-2.16), any
      shortness of breath at rest (OR 2.81, 95% CI 1.83-4.30), recent wheeze (OR 1.71,
      95% CI 1.04-2.82), recent attacks of shortness of breath with wheeze (OR 1.85,
      95% CI 1.05-3.26), asthma diagnosis/symptoms (OR 1.50, 95% CI 1.09-2.08),
      diagnosis of asthma or bronchitis/emphysema (obstructive lung diseases (OLD)) (OR
      2.24, 95% CI 1.40-3.58), current cough/phlegm (OR 1.52, 95% CI 1.07-2.15), and
      rhino-conjunctivitis (OR 1.48, 95% CI 1.13-1.94). Exposure only at work yielded
      higher adjusted odds ratios for all health conditions, except for rhino
      conjunctivitis. Overall, about 24% of shortness of breath at rest, 16% of
      dyspnoea, 17% of rhino-conjunctivitis, 12% of OLD, and 10% of asthma
      diagnosis/symptoms are attributable to the effect of exposures to both husband
      and at work. Twelve percent of shortness of breath at rest and 10% of rhino
      conjunctivitis cases might be avoided by eliminating exposure only at work and
      only to husband, respectively. CONCLUSIONS: Lifetime ETS exposure, especially at
      work, is associated with respiratory symptoms/diseases, and it accounts for a
      sizeable proportion of such disorders. The combined effect of both exposures is
      higher than the separate effects.

PMID- 16893639
TI  - Exhaled CO, a predictor of lung function?
AB  - BACKGROUND: Smoking is associated with an accelerated loss of lung function and
      inhalation accelerates the decline further. Exhaled CO reflects the exposure of
      smoke to the lungs. AIM: To investigate whether self-reported inhalation and type
      of cigarette influenced the level of exhaled CO and whether CO could provide
      additional information to usual measures of smoking regarding prediction of
      present lung function and decline in lung function over an extended period of
      time. METHOD: Cigarette smokers from the Copenhagen City Heart Study with valid
      measures of lung function and exhaled CO; in total 3738 subjects, 2096 women and
      1642 men. RESULTS: Subjects not inhaling had slightly lower exhaled CO values
      than those inhaling, but substantially higher values than non-smokers (P<0.001).
      Smokers of plain cigarettes had slightly lower CO values than smokers of filter
      cigarettes (P<0.001). Increasing CO levels were correlated to a lower FEV(1)%pred
      and to an accelerated decline in lung function. However, in multiple linear
      regression analyses these correlations were not significant. CONCLUSION:
      Inhalation and type of cigarette affects exhaled CO levels. CO measures have no
      predictive value regarding neither present lung function nor decline in lung
      function with time in a population survey setting.

PMID- 16893640
TI  - Electrochemical immunosensor array using a 96-well screen-printed microplate for
      aflatoxin B1 detection.
AB  - A novel analytical immunosensor array, based on a microtiter plate coupled to a
      multichannel electrochemical detection (MED) system using the intermittent pulse
      amperometry (IPA) technique, is proposed for the detection of aflatoxin B1
      (AFB1). In the present work, the electrochemical behaviour and electroanalytical
      performance of the thick-film carbon sensors (also designated as screen-printed
      electrodes) incorporated in the multichannel electrochemical plate were first
      evaluated. Then the 96-well screen-printed microplate was modified in accord with
      a competitive indirect enzyme-linked immunoassay (ELISA) format for aflatoxin B1
      detection. The measurements were performed using both spectrophotometric and
      electrochemical procedures and the results of the calibration curves, detection
      limit (LOD), sensitivity and reproducibility of the respective assay systems were
      evaluated. The immunoassay was then applied for analysis of corn samples spiked
      with AFB1 before and after the extraction treatment, in order to study the
      extraction efficiency and the matrix effect, respectively. These studies have
      shown that using this system, AFB1 can be measured at a level of 30 pg/mL and
      with a working range between 0.05 and 2 ng/mL. Good recoveries (103+/-8%) were
      obtained, demonstrating the suitability of the proposed assay for accurate
      determination of the AFB1 concentration in corn samples. The specificity of the
      assay was assessed by studying the cross-reactivity of PAb relative to AFB1. The
      results indicated that the PAb could readily distinguish AFB1 from other
      aflatoxins, with the exception for AFG1.

PMID- 16893641
TI  - Pathological response to preoperative concurrent chemo-radiotherapy for breast
      cancer: results of a phase II study.
AB  - This study evaluated, in terms of pathological complete response (pCR) and acute
      toxicity, preoperative concurrent (5-fluorouracil (5-FU)-vinorelbine)
      chemoradiotherapy for large breast cancers. A total of 60 women were included in
      the study. Chemotherapy consisted of 4 cycles of 5-FU, 500 mg/m2/d, continuous
      infusion (d1-d5) and vinorelbine, 25 mg/m2 (d1; d6). Starting with the second
      cycle, radiotherapy delivered 50 Gy to the breast and 46 Gy to the internal
      mammary and supra/infra-clavicular lymph nodes. Breast surgery and axillary lymph
      node dissection were then performed. Four patients did not complete their
      chemotherapy. Breast conservation was possible in 69% of patients. The rate of
      pCR was 27%. Three factors were associated with pCR: histological grade 3,
      absence of hormonal receptors and high mitotic index. Grade 4 haematological
      toxicity occurred in 22% of patients. In conclusion, chemoradiotherapy
      demonstrated good efficacy, both in terms of pCR and in allowing breast
      conservation with acceptable tolerance.

PMID- 16893642
TI  - A randomised phase III study comparing high-dose chemotherapy to conventionally
      dosed chemotherapy for stage III ovarian cancer: the Finnish Ovarian Cancer
      (FINOVA) study.
AB  - Women with stage III ovarian cancer and with < or = 2 cm residual tumour were
      randomly assigned to receive either conventionally dosed chemotherapy (group A)
      or HDCT (group B). Patients allocated to group A received 6 cycles of paclitaxel
      (T) 135 mg/m2 and cisplatin (P) 75 mg/m2 every 3 weeks, and those allocated to
      HDCT received 3 TP cycles followed by peripheral blood stem cell mobilisation
      with cyclophosphamide (C) 3000 mg/m2 and T 175 mg/m2, and subsequently HDCT with
      carboplatin 1500 mg/m2, C 120 mg/kg, and mitoxantrone 75 mg/m2. The trial was
      closed early after 42 patients were entered due to slow accrual. The median
      follow-up time of patients who were alive was 81 months. The median progression
      free survival time was 15.9 and 16.6 months (hazard ratio, HR 0.83; 95% CI 0.41
      1.69, P = 0.61) and the median overall survival time was 43.7 and 64.3 months
      (HR, 0.74; 95% CI 0.34-1.61, P = 0.44) in groups A and B, respectively. Although
      one patient died of HDCT-related toxicity, the regimen was otherwise relatively
      well tolerated. We conclude that the HDCT regimen used was feasible, but did not
      result in significantly improved survival in this prematurely closed trial. A
      clinically important survival benefit cannot be excluded due to the small sample
      size.

PMID- 16893643
TI  - Regulation of hepatic steroid receptors and enzymes by the 3beta-hydroxysteroid
      dehydrogenase inhibitor trilostane.
AB  - Therapies designed to treat hypercortisolism have usually sought to reduce
      circulating glucocorticoid concentrations, however the local tissue endocrine
      environment could be an alternative target. The 3beta-hydroxysteroid
      dehydrogenase Delta5-4 isomerase (3beta-HSD) inhibitor trilostane is of interest,
      since, although it is only moderately and transiently effective in reducing
      circulating steroid, it is remarkably effective in alleviating Cushing's symptoms
      in veterinary applications. To seek alternative modes of action, male Wistar rats
      were treated with trilostane. Although final circulating corticosteroid
      concentrations were unaffected, liver 11beta-hydroxysteroid dehydrogenase type 2
      (11beta-HSD2) transcription and translation was significantly increased, whereas
      3beta-HSD was not affected either in liver or adrenal. Glucocorticoid receptor
      (GR) mRNA was down-regulated, and mineralocorticoid receptor (MR) up-regulated by
      trilostane treatment: no changes in 11beta-HSD1 mRNA were observed. Trilostane
      also had no direct effect on GR response element-mediated gene transcription. The
      results show that the tissue endocrine environment is affected by trilostane
      treatment in the absence of sustained changes in circulating corticosteroid. The
      combination of increased 11beta-HSD2 and reduced GR expression in target organs
      could be expected to ameliorate the effects of excess glucocorticoid, suggesting
      new therapeutic approaches.

PMID- 16893644
TI  - Determination of androgen bioactivity in human serum samples using a recombinant
      cell based in vitro bioassay.
AB  - The present study describes the development and optimization of a cell-based
      reporter assay for the determination of androgen bioactivity levels in human
      serum samples. Towards this end, human embryonic kidney (HEK) 293 cells were
      cotransfected with two plasmids, one encoding the mouse mammary tumor virus
      (MMTV)-driven luciferase reporter gene and the other the SV40 promoter-driven
      human androgen receptor (AR), and a stable cell line, expressing human AR and
      androgen-responsive luciferase was established by antibiotic selection. RT-PCR
      confirmed proper transcription and stable integration of AR in the cell line. On
      stimulation of the cells with testosterone (T) for 24h, luciferase activity was
      increased in dose-dependent fashion up to 15-fold, with the minimum effective
      concentration of T being 0.03 nmol/l. T-induced reporter gene expression of the
      cells was inhibited by the anti-androgens cyproterone acetate and
      hydroxyflutamide. Upon stimulation with non-androgenic steroids like estradiol,
      progesterone, dexamethasone and cortisol, the cells showed only marginal activity
      except for a weak glucocorticoid effect at high concentration. The cells also
      responded well to various chemicals (mostly pesticides, their metabolites and
      common industrial chemicals) with known androgenic activity. The cell line was
      further optimized by measuring the levels of androgens from male and female serum
      samples. Our data indicated that the cells can be used to estimate androgen
      bioactivity in serum of females suffering from polycystic ovary syndrome (PCOS)
      and males of different age groups. In conclusion, we demonstrate that the
      bioassay based on this cell line provides a reliable method to determine serum
      levels of androgen bioactivity from biological samples even at the low
      concentrations present in female circulation. The 96-well plate format makes the
      assay suitable for high throughput measurements.

PMID- 16893645
TI  - Metabolism of tibolone and its metabolites in uterine and vaginal tissue of rat
      and human origin.
AB  - In postmenopausal women, tibolone shows clear tissue differences in its
      stimulatory effects on the vagina and uterus. In rats, however, it has
      stimulatory effects on both tissues, with a different, more estrogenic, effect on
      the uterus than in humans. This may be due to differences in local metabolism.
      Therefore, in the present study, the metabolism of tibolone was analyzed in
      incubations of uterine and vaginal tissue from postmenopausal women and
      ovariectomized rats using radiolabeled tibolone in order to understand the tissue
      and species-specific metabolism. In the rat, tibolone (50 nM) was mainly 3alpha
      reduced to the estrogenic 3alpha-OH-tibolone in the uterus and vagina. The 3beta
      OH tibolone can be isomerized to 3alpha-OH-tibolone with tibolone as
      intermediate. In contrast, in the same tissues from postmenopausal women, the
      progestagenic Delta4-isomer and estrogenic 3beta-OH-tibolone were the major
      metabolites of tibolone. The formation of the Delta4-isomer was higher in uterine
      tissue. The 3beta-hydroxysteroid dehydrogenase (HSD) inhibitor epostane had no
      effect on tibolone metabolism in human uterine and vaginal tissue microsomes and
      HEK293 cells expressing the human 3beta-HSD types 1 and 2 isoforms did not
      metabolize tibolone. Moreover, the 3beta-reduction of tibolone to 3beta-OH
      tibolone was NADPH dependent, while the isomerization of tibolone to the Delta4
      isomer did not require a cofactor. It was therefore concluded that human 3beta
      HSD isoforms are not involved in the metabolism of tibolone, and that the 3beta
      reduction and the Delta5-10 to Delta4 isomerization may be catalyzed by different
      enzymes. In conclusion, we showed that, in hormone therapy target tissues of the
      rat as compared with the human, different metabolic pathways for tibolone exist
      and therefore result in metabolites with different pharmacological properties.
      The rat is therefore a poor model to predict the effects of tibolone on the
      uterus in postmenopausal women.

PMID- 16893646
TI  - Allergic reactions to patent blue dye.

PMID- 16893647
TI  - Synthesis and biological evaluation of benzamides and benzamidines as selective
      inhibitors of VEGFR tyrosine kinases.
AB  - A series of benzamidines and benzamides was synthesized as selective inhibitors
      of vascular endothelial growth factor receptor (VEGFR) tyrosine kinases, and
      tested for inhibitory activity toward autophosphorylation by the enzyme assay.
      Selective inhibition of VEGFR-2 tyrosine kinase was observed in the salicylic
      amide 4e and the anthranilic amidine 5a, and their percent inhibitions of VEGFR-2
      tyrosine kinase were 44-60% at a 10 microM concentration of compounds. The
      salicylic amide 4a showed inhibition of both VEGFR-1 and VEGFR-2 tyrosine kinases
      at a 10 microM concentration.

PMID- 16893648
TI  - The structure and regulation of vinculin.
AB  - Vinculin is a ubiquitously expressed actin-binding protein frequently used as a
      marker for both cell-cell and cell-extracellular matrix (focal adhesion) adherens
      type junctions, but its function has remained elusive. Vinculin is made up of a
      globular head linked to a tail domain by a short proline-rich sequence, and an
      intramolecular interaction between the head and tail masks the numerous ligand
      binding sites in the protein. Determination of the crystal structure of vinculin
      has shed new light on the way that these ligand-binding sites are regulated. The
      picture that emerges is one in which vinculin stabilizes focal adhesions and
      thereby suppresses cell migration, an effect that is relieved by transient
      changes in the local concentrations of inositol phospholipids. However, the
      finding that vinculin modulates the signalling pathways involved in apoptosis
      suggests that additional roles for vinculin remain to be discovered.

PMID- 16893649
TI  - IL-10 and susceptibility to Coccidioides immitis infection.

PMID- 16893651
TI  - Novel diphenyl ethers: design, docking studies, synthesis and inhibition of enoyl
      ACP reductase of Plasmodium falciparum and Escherichia coli.
AB  - We designed some novel diphenyl ethers and determined their binding energies for
      Enoyl-Acyl Carrier Protein Reductase (ENR) of Plasmodium falciparum using
      Autodock. Out of these, we synthesized the promising compounds and tested them
      for their inhibitory activity against ENRs of P. falciparum as well as
      Escherichia coli. Some of these compounds show nanomolar inhibition of PfENR and
      low micromolar inhibition of EcENR. They also exhibit low micromolar potency
      against in vitro cultures of P. falciparum and E. coli. The study of structure
      activity relationship of these compounds paves the way for further improvements
      in the design of novel diphenyl ethers with improved activity against purified
      enzyme and the pathogens.

PMID- 16893650
TI  - Structure-activity relationships in platelet-activating factor. Part 13:
      synthesis and biological evaluation of piperazine derivatives with dual anti-PAF
      and anti-HIV-1 or pure antiretroviral activity.
AB  - HIV-1 infection of the brain and PAF neurotoxicity are implicated in AIDS
      dementia complex. We previously reported that a trisubstituted piperazine
      derivative is able to diminish both HIV-1 replication in monocyte-derived
      macrophages and PAF-induced platelet aggregation. We report in this work new
      compounds obtained by modifying its piperazine substituents. The structure
      activity relationship study shows that a better dual activity or even pure
      antiretroviral compounds can be obtained in this series.

PMID- 16893652
TI  - Complete autologous reconstruction of the aorta and the pulmonary bifurcation in
      truncus arteriosus communis.
AB  - Truncus arteriosus communis is a congenital heart malformation, which is usually
      repaired in the neonatal period or early infancy. Although results of repair are
      good, there is long-term morbidity caused by reoperations mainly owing to right
      ventricle to pulmonary artery conduit exchange or stenosis at the pulmonary
      artery bifurcation as recently reported for Contegra conduits. We present a new
      technique for complete autologous reconstruction of the aorta and the pulmonary
      bifurcation in truncus arteriosus type I and II.

PMID- 16893653
TI  - Vacuum treatment of pectus excavatum.

PMID- 16893654
TI  - Acute interstitial pneumonia following surgery for primary lung cancer.
AB  - OBJECTIVE: Although acute interstitial pneumonia is a life-threatening
      complication following surgery for lung cancer, the cause and risk factors for
      acute interstitial pneumonia remain unknown. We conducted this study to determine
      the characteristics of acute interstitial pneumonia after pulmonary resection and
      to identify the risk factors for this disease. METHODS: We experienced 16 (2.0%)
      cases of acute interstitial pneumonia among 822 patients who underwent pulmonary
      resection for primary lung cancer over a period of 12 years. We performed a
      retrospective analysis of these patients, comprising the patients' background,
      the operative procedure, the radiographic characteristics and the prognosis.
      RESULTS: In all patients, the shadow appeared within 1 week after the operation.
      Twelve patients required mechanical ventilatory support due to the development of
      respiratory failure. The site of the tumor (right side), preoperative radiation
      or chemotherapy, pneumonectomy, blood transfusion, and intraoperative
      complication were independent risk factors for the incidence of acute
      interstitial pneumonia (P=0.001, 0.0484, 0.0012, 0.0002, 0.0003, respectively) in
      the multivariate analysis. Nine of the 16 patients died due to respiratory
      failure, resulting in a mortality rate of 56.3%. The maximum amount of lactate
      dehydrogenase (LDH) in the operative death patients was significantly higher than
      that in the survivors (472+/-138IU/l vs 257+/-79IU/l, respectively, P=0.0031).
      CONCLUSIONS: We concluded that in order to reduce the incidence of acute
      interstitial pneumonia, it is necessary to perform careful postoperative
      management for patients who are male, have right lung disease, have undergone
      preoperative chemo or radiation therapy, or have undergone pneumonectomy.

PMID- 16893655
TI  - Predicted versus observed FEV1 in the immediate postoperative period after
      pulmonary lobectomy.
AB  - OBJECTIVE: Scanty information can be found regarding ppoFEV1% correlation with
      true FEV1% in the immediate days after surgery, when most cardio-respiratory
      complications are developed. This prospective multicentric investigation aims to
      describe the evolution of FEV1 in a series of uneventful lobectomy cases before
      hospital discharge, and to identify factors associated with the variation of
      postoperative residual FEV1, with the ratio between the actual and the predicted
      postoperative FEV1 measured during the first 6 postoperative days. METHODS: One
      hundred and sixty-one patients submitted to lobectomy were prospectively enrolled
      in the study. Patients with chest wall resections and postoperative complications
      were excluded. Data from a total of 125 patients were thus used for the analysis.
      The following clinical variables were recorded: age, preoperative FEV1, ppoFEV1,
      presence of chronic obstructive pulmonary disease (COPD), surgical approach (VATS
      or muscle-sparing thoracotomy), side (right or left) and site (upper or lower) of
      resection, type of analgesia (epidural or intravenous), and daily visual analogue
      pain score (VAS). FEV1 was measured in every patient at hospital admission and
      daily until discharge or up to postoperative day 6. Random effects time-series
      cross-sectional regression analyses were performed to identify factors associated
      with variation of postoperative residual function (100-(preoperative FEV1
      postoperative FEV1/preoperative FEV1 x 100)), and of FEV1 ratio ((actual
      postoperative FEV1 x 100)/ppoFEV1). For these analyses, the dependent variables
      (postoperative residual function and FEV1 ratio) and the pain score were analysed
      as panel longitudinal data. The regression analyses were subsequently validated
      by bootstrap procedure. RESULTS: FEV1% was lower at first postoperative day and
      increased gradually up to day 6 but mean values never reached ppoFEV1%. Pain
      scores decreased from day 1 to day 6. Preoperative FEV1 (p<0.0001) and
      postoperative pain score (p<0.0001) resulted independently and reliably inversely
      associated with postoperative residual FEV1 (model R2, 0.16). Preoperative FEV1
      (p=0.001), postoperative pain score (p<0.0001), and epidural analgesia (p=0.04)
      resulted independently and reliably associated with postoperative FEV1 ratio
      (model R2, 0.13). CONCLUSION: Current methods of prediction of postoperative FEV1
      greatly underestimated the real functional loss in the immediate postoperative
      period. Therefore, for the purpose of a more accurate risk stratification we need
      to correct the traditional prediction of postoperative FEV1.

PMID- 16893656
TI  - Tumor and viral recognition by natural killer cells receptors.
AB  - Natural killer (NK) cells destroy hazardous cells such as tumors and virus
      infected cells immediately without the need for prior antigen stimulation. The
      activation of NK cells largely depends on the recently identified natural
      cytotoxic receptors (NCRs), which include three members: NKp46, NKp44 and NKp30.
      The NCRs are unique in their expression pattern that is almost conclusively
      confined to NK cells, and in their broad specificity towards a wide range of
      targets. However, very little is known about the ligands identity of the NCRs and
      so far the only ligands known are two virally derived molecules: the
      hemagglutinin protein of influenza viruses that directly binds and activates two
      of the NCRs; NKp46 and NKp44, and the human cytomegalovirus tegument protein,
      pp65, which binds the NKp30 receptor and inhibits its activation thus promoting
      survival of the virus. In this review we describe the function of the NCRs in
      various pathological conditions with a special emphasis on tumor targeting.

PMID- 16893657
TI  - Nuclear and cytoplasmic mRNA quantification by SYBR green based real-time RT-PCR.
AB  - Measurement of the steady-state abundance of nuclear and cytoplasmic RNA requires
      efficient subcellular fractionation and RNA recovery coupled with accurate
      quantification of individual RNA species. Detergent lysis of tissue culture cells
      provides a simple fractionation procedure that can be optimized to individual
      cell lines. The large dynamic range, extreme sensitivity, high sequence
      specificity, and fast turn-around time has allowed real-time reverse
      transcription polymerase chain reaction (real-time RT-PCR) to become a standard
      tool for mRNA quantification. Among the different chemistries used for PCR
      product detection during amplification, DNA binding dyes such as SYBR Green I are
      simple, versatile, and yet highly reliable and least expensive. With attention to
      primer design and cycling conditions, virtually any mRNA species can be
      accurately quantified from even minute quantities of starting RNA. This method
      provides an accurate and efficient procedure for estimating the relative ratios
      of nuclear and cytoplasmic RNA concentrations.

PMID- 16893658
TI  - Bacterial production of biologically active canine interleukin-1beta by seamless
      SUMO tagging and removal.
AB  - Interleukin 1beta (IL-1beta) is a potent stimulator of extracellular matrix
      degradation in models of osteoarthritis (OA). In contrast to bovine explant
      models which effectively respond to recombinant human IL-1beta, canine models are
      relatively refractory to human IL-1beta stimulation. Canine IL-1beta cDNA was
      cloned in order to produce a fully potent species matched preparation of IL-1beta
      for use specifically in canine models of OA. Established methods for the
      production of various orthologous IL-1beta proteins from different species are
      problematic due to the exquisite sensitivity of the mature IL-1beta product to N
      terminal variations and the intrinsic technical challenges associated with
      producing an unmodified product. We have applied a seamless method of SUMO
      tagging and removal in order to produce a homogeneous unmodified preparation of
      canine IL-1beta from Escherichia coli which was found to be a potent inducer of
      aggrecanase activity in isolated canine articular chondrocytes. This method
      combines highly efficient aspects of seamless plasmid engineering, protein
      purification, and precise tag removal.

PMID- 16893659
TI  - A novel esterase from Ralstonia sp. M1: gene cloning, sequencing, high-level
      expression and characterization.
AB  - A newly isolated gene from Ralstonia sp. M1, encoding an esterase, was cloned in
      Escherichia coli and its nucleotide sequence determined. The 1.6kb insert
      revealed one complete open reading frame, predicted to encode an esterase (320
      aa, 34.1kDa) with a pI of 9.86. EstR contained a putative oxyanion hole H36G37, a
      conserved pentapeptide G103HSLG107 and a conserved catalytic His265 and Asp237.
      The EstR sequence shared 64-70 and 44-48% identity with the
      hydrolases/acyltransferases from Burkholderia strains and from Ralstonia strains,
      respectively, 44 and 38% identity with the lactone-specific esterase from
      Pseudomonas fluorescens and Mesorhizobium loti, respectively. The esterase EstR
      was expressed with a high level of 41mg/g wet cells. The Ni-NTA-purified esterase
      EstR showed an optimal activity in the temperature range 60-65 degrees C and pH
      range 7.5-9.0 towards p-nitrophenyl caproate. The enzyme was found to be highly
      resistant to many organic solvents especially induced by ethanolamine. Metal ions
      showed slight effect on esterase activity. The inhibitor phenylmethanesulfonyl
      fluoride inhibited strongly the esterase. Triton X-45 induced the activation of
      EstR, but other detergents slightly to strongly decreased or completely
      inhibited. Among tested p-NP esters, caproate was the most preferential substrate
      of this esterase.

PMID- 16893660
TI  - Efficacy and safety of levetiracetam in clinical practice: results of the SKATE
      trial from Belgium and The Netherlands.
AB  - OBJECTIVE: Aim of the study was to assess the efficacy and safety of
      levetiracetam as add-on treatment in patients with partial-onset epilepsy in
      clinical practice. METHODS: In this observational, multi-centre study patients
      were treated with levetiracetam for 16 weeks. From a starting dose of 1000
      mg/day, dose levels were adjusted at 2-weekly intervals in 1000-mg steps, to a
      maximum of 3000 mg/day, based on seizure control and tolerance. Analysis of
      efficacy was based on reduction in seizure frequency relative to baseline, 50%
      and 100% responder rates (for partial seizures and all seizure types combined)
      and percentage of patients using levetiracetam at the end of the study. Analysis
      of safety was based on occurrence of adverse events. RESULTS: The present
      analysis concerns the results of patients recruited in Belgium and The
      Netherlands. Of the 251 patients included in the study, 86.9% completed 16 weeks
      of treatment. Reduction in frequency of partial-onset seizures was 62.2%, with
      19.3% of the patients becoming seizure free and 56.6% having a reduction in
      seizure frequency of > or = 50%. These percentages were more or less the same
      when calculated for all seizure types combined. Tolerance of levetiracetam
      treatment was good, with most adverse events being only mild to moderate in
      severity, and only 10.0% of the adverse events leading to discontinuation from
      the study. Asthenia, somnolence, dizziness and headache were the most frequently
      reported adverse events. CONCLUSION: Levetiracetam is effective and safe as add
      on treatment for partial-onset seizures in clinical practice.

PMID- 16893661
TI  - Ictal spitting in left temporal lobe epilepsy: report of three cases.
AB  - PURPOSE: Ictal spitting is rarely reported in patients with epilepsy. More often
      it is observed in patients with temporal lobe epilepsy (TLE) and is presumed to
      be a lateralizing sign to language nondominant hemisphere. We report three
      patients with left TLE who had ictal spitting registered during prolonged video
      EEG monitoring. METHODS: Medical charts of all patients with medically refractory
      partial epilepsy submitted to prolonged video-EEG monitoring in the Epilepsy Unit
      at UNIFESP during a 3-year period were reviewed, in search of reports of ictal
      spitting. The clinical, neurophysiological and neuroimaging data of the
      identified patients were reviewed. RESULTS: Among 136 patients evaluated with
      prolonged video-EEG monitoring, three (2.2%) presented spitting automatisms
      during complex partial seizures. All of them were right-handed, and had clear
      signs of left hippocampal sclerosis on MRI. In two patients, in all seizures in
      which ictal spitting was observed, EEG seizure onset was seen in the left
      temporal lobe. In the third patient, ictal onset with scalp electrodes was
      observed in the right temporal lobe, but semi-invasive monitoring with foramen
      ovale electrodes revealed ictal onset in the left temporal lobe, confirming false
      lateralization in surface records. The three patients became seizure-free
      following left anterior temporal lobectomy. CONCLUSIONS: Ictal spitting is a rare
      finding in patients with epilepsy, and may be considered a localizing sign of
      seizure onset in the temporal lobe. It may be observed in seizures originating
      from the left temporal lobe, and thus should not be considered a lateralizing
      sign of nondominant TLE.

PMID- 16893662
TI  - Susceptibility of vaginal bacteria to metronidazole and tinidazole.
AB  - In vitro antimicrobial susceptibility testing was performed on 470 vaginal
      isolates from women with bacterial vaginosis and three species of Lactobacillus,
      to metronidazole and tinidazole using the agar dilution method. There was no
      significant difference observed in the inhibitory activity of either drug to any
      of the isolates tested.

PMID- 16893663
TI  - Preliminary ten year results from a randomised single centre mass screening trial
      for abdominal aortic aneurysm.
AB  - BACKGROUND: At present, several regions and countries are considering screening
      for abdominal aortic aneurysm (AAA). However, The Chichester Aneurysms Screening
      Trial has reported poor long term benefit of screening for AAA. We therefore
      supplement previously published data with a preliminary analysis of the ten-year
      mortality from AAA, based upon population-based data until 2002 (7 years) and
      incomplete hospital-based information on deaths until 2005 (10 years). METHODS
      AND MATERIAL: In 1994 we started a randomised screening trial of 12,639 64-73
      year-old males; 6,306 were controls, and 6,333 were invited to an abdominal
      ultrasound scan at their district hospital. Information on all deaths until
      15.3.2005 was obtained from the Office of Civil Registration. Information on AAA
      related deaths was obtained from the national registry of Causes of Deaths from
      1.4.1994 to 31.12.2001, and supplemented with AAA deaths known to the Danish
      National Patient Registry until 15.3.2005. Operations were obtained from the
      Danish National Vascular Registry from 1.4.1994 to 15.3.2005. Death certificates
      and medical records were reviewed by two independent assessors. The analyses were
      based on "intention to treat" from the date of randomisation. RESULTS: The
      attendance rate was 76.6% and 191 (4.0%) had an AAA. The median observation time
      was 9.58 years. In the invited group 13 subjects were acutely operated on
      compared to 40 in the control group (Risk ratio: 0.32 (95% C.I. 0.17-0.60,
      P<0.001)), and 14 died due to AAA compared to 51 in the control group (Hazard
      ratio: 0.27 (95% C.I.: 0.15-0.49, P<0.001). CONCLUSION: Over ten years, screening
      reduced mortality from AAA by 73%, and the frequency of emergency operations by
      68%.

PMID- 16893664
TI  - Relatively high pulmonary and cardiovascular mortality rates in screening
      detected aneurysmal patients without previous hospital admissions.
AB  - BACKGROUND: Men with abdominal aortic aneurysm (AAA) who are not hospitalised for
      pulmonary and cardiovascular diseases may have higher mortality due to such
      disorders. MATERIAL AND METHODS: Previous discharge diagnoses and causes of death
      were collected for 4,816 men aged 64-73 years attending mass screening for AAA.
      Of these, 191 (4%) had an AAA. Overall, cardiovascular- and pulmonary-disease
      specific mortality was compared for men with and without AAA stratified for
      earlier pulmonary or cardiovascular hospitalisations by Cox's proportional
      hazards regression while adjusting for age. Absolute risk differences after five
      years were calculated by life table analysis. RESULTS: The median observation
      time was 63 months. 362 men died from cardiovascular causes other than AAA, and
      144 died from pulmonary causes. The cardiovascular mortality was significantly
      higher in aneurysm patients without previous related hospitalisation (HR=4.35,
      95% CI: 2.73-6.94, P<0.001) with an absolute mortality difference after 5 years
      of 16.3% (95% CI: 10.2-22.5%). Pulmonary-cause mortality was higher among men
      with AAA both with and without previous hospitalisation for pulmonary causes
      (HR=3.05; 95% CI: 1.19-7.83, P=0.020, and HR=3.29; 95% CI: 1.78-6.08, P<0.001,
      respectively). CONCLUSIONS: Men with AAA who had not been hospitalised for
      cardiovascular diseases have more than four times higher cardiovascular
      mortality. Studies of cohorts being offered relevant prophylaxis may clarify the
      potential benefits of general preventive actions.

PMID- 16893665
TI  - Endovascular treatment of Takayasu's arteritis of the thoracic descending aorta.

PMID- 16893666
TI  - Effects of a 30-km race upon salivary lactate correlation with blood lactate.
AB  - Blood lactate has been used to determine the aerobic capacity and long distance
      performance. Recently, a new methodology has been suggested to supplant the
      invasive blood lactate techniques. Salivary lactate has received attention
      because it shows high correlation to blood lactate in progressive overload test.
      We evaluated the correlation between salivary and blood lactate during a long
      distance run and assessed possible changes in salivary lactate concentration.
      Fifteen expert marathon racers ran 30 km as fast as possible. Saliva and 25 muL
      of blood were collected at rest and at each 6 km for lactate determination. Blood
      lactate concentration increased in the 6th km and then remained constant until
      the end of the race. Salivary lactate increased after 18 km in relation to basal.
      We found high correlations between blood and saliva absolute lactate (r=0.772,
      p<0.05) and the blood lactate relative concentration corrected by protein
      (r=0.718, p<0.05). The highest correlation found between absolute and relative
      salivary lactate was r=0.994 (p<0.001). Our results show that it is possible to
      use salivary lactate with absolute values or relative protein concentration. In
      addition, salivary lactate showed a high correlation with blood lactate in
      endurance events.

PMID- 16893667
TI  - Insulin-like growth factor binding protein 2 is a marker for antiestrogen
      resistant human breast cancer cell lines but is not a major growth regulator.
AB  - Antiestrogens target the estrogen receptor and counteract the growth stimulatory
      action of estrogen on human breast cancer. However, acquired resistance to
      antiestrogens is a major clinical problem in endocrine treatment of breast cancer
      patients. To mimic acquired resistance, we have used a model system with the
      antiestrogen sensitive human breast cancer cell line MCF-7 and several
      antiestrogen resistant cell lines derived from the parental MCF-7 cell line. This
      model system was used to study the expression and possible involvement in
      resistant cell growth of insulin-like growth factor binding protein 2 (IGFBP-2).
      By an oligonucleotide based microarray, we compared the expression of mRNAs
      encoding insulin-like growth factor binding protein 1,2,3,4,5 and 6 (IGFBP-1 to 
      6) in the parental MCF-7 cell line to three human breast cancer cell lines,
      resistant to the antiestrogen ICI 182,780 (Faslodex/Fulvestrant). Only IGFBP-2
      mRNA was overexpressed in all three resistant cell lines. Thus, we compared the
      IGFBP-2 protein expression in MCF-7 cells to nine antiestrogen resistant breast
      cancer cell lines, resistant to either ICI 182,780 or tamoxifen or RU 58,668 and
      found that IGFBP-2 was overexpressed in all nine resistant cell lines. Three of
      the resistant cell lines, resistant to different antiestrogens, were selected for
      further studies and IGFBP-2 overexpression was demonstrated at the mRNA level as
      well as the intra- and extracellular protein level. The objective of this study
      was to examine if IGFBP-2 is involved in growth of antiestrogen resistant human
      breast cancer cells. Therefore, IGFBP-2 expression was inhibited by antisense
      oligonucletides and siRNA. Specific inhibition of IGFBP-2 protein expression was
      achieved in MCF-7 and the three selected antiestrogen resistant cell lines, but
      no effect on resistant cell growth was observed. Thus, we were able to establish
      IGFBP-2 as a marker for antiestrogen resistant breast cancer cell lines, although
      IGFBP-2 was not a major contributor to the resistant cell growth.

PMID- 16893668
TI  - Cervical dystonia as a presenting symptom of Parkinson's disease.

PMID- 16893669
TI  - Modulation of ERK 1/2 and p38 MAPK signaling pathways by ATP in osteoblasts:
      involvement of mechanical stress-activated calcium influx, PKC and Src
      activation.
AB  - There is evidence that extracellular nucleotides, acting through multiple P2
      receptors, may play an important role in the regulation of bone metabolism by
      activating intracellular signaling cascades. We have studied the modulation of
      mitogen-activated protein kinase (MAPK) signaling pathways and its relationship
      to changes in intracellular calcium concentration ([Ca(2+)](i)) induced by ATP in
      ROS-A 17/2.8 osteoblastic cells. ATP and UTP (10 microM) increased [Ca(2+)](i) by
      cation release from intracellular stores. We have found that when the cells are
      subsequently subjected to mechanical stress (medium perturbation), a transient
      calcium influx occurs. This mechanical stress-activated calcium influx (MSACI)
      was not observed after ADP stimulation, indicating that P2Y(2) receptor
      activation is required for MSACI. In addition, ERK 1/2 and p38 MAPK were
      activated by ATP in a dose- and time-dependent manner. This activation was almost
      completely blocked using neomycin (2.5mM), an inhibitor of phosphoinositide
      phospholipase C (PI-PLC), Ro 318220 (1 microM), a protein kinase C (PKC)
      inhibitor, and PP1 (50 microM), a potent and selective inhibitor of the Src
      family tyrosine kinases. Ca(2+)-free extracellular medium (containing 0.5mM EGTA)
      and the use of gadolinium (5 microM), which suppressed MSACI, prevented ERK 1/2
      and p38 phosphorylation by ATP. Altogether, these results represent the first
      evidence to date suggesting that P2Y(2) receptor stimulation by ATP in
      osteoblasts sensitizes mechanical stress activated calcium channels leading to
      calcium influx and a fast activation of the ERK 1/2 and p38 MAPK pathways. This
      effect also involves upstream mediators such as PI-PLC, PKC and Src family
      kinases.

PMID- 16893670
TI  - External Qi of Yan Xin Qigong differentially regulates the Akt and extracellular
      signal-regulated kinase pathways and is cytotoxic to cancer cells but not to
      normal cells.
AB  - Long-term clinical observations and ongoing studies have shown significant
      antitumor effect of external Qi of Yan Xin Qigong which originated from
      traditional Chinese medicine. In order to understand the molecular and cellular
      mechanisms underlying the antitumor effect of external Qi of Yan Xin Qigong, we
      have examined its cytotoxic effect on BxPC3 pancreatic cancer cells and its
      effect on the Akt and extracellular signal-regulated kinase pathways. We found
      that external Qi of Yan Xin Qigong dramatically inhibited basal phosphorylation
      levels of Akt and extracellular signal-regulated kinases, epidermal growth factor
      mediated phosphorylation of extracellular signal-regulated kinases, and
      phosphatidylinositol 3-kinase activity. External Qi of Yan Xin Qigong also
      inhibited constitutive and inducible activities of nuclear factor-kappa B, a
      target of the Akt and epidermal growth factor receptor pathways. Furthermore, a
      single 5min exposure of BxPC3 cells to external Qi of Yan Xin Qigong induced
      apoptosis, accompanied by a dramatic increase of the sub-G1 cell population, DNA
      fragmentation, and cleavage of caspases 3, 8 and 9, and poly(ADP-ribose)
      polymerase. Prolonged treatment with external Qi of Yan Xin Qigong caused rapid
      lysis of BxPC3 cells. In contrast, treatment of fibroblasts with external Qi of
      Yan Xin Qigong induced transient activation of extracellular signal-regulated
      kinases and Akt, and caused no cytotoxic effect. These findings suggest that
      external Qi of Yan Xin Qigong may differentially regulate these survival pathways
      in cancer versus normal cells and exert cytotoxic effects preferentially on
      cancer cells, and that it could potentially be a valuable approach for therapy of
      pancreatic carcinomas.

PMID- 16893672
TI  - Poorly known relatives of Arabidopsis thaliana.
AB  - Non-model Arabidopsis species have been widely used as outgroup taxa in studies
      of molecular evolution. In Arabidopsis lyrata, Arabidopsis halleri and
      Arabidopsis arenosa, traits pertaining to self-incompatibility, heavy metal
      tolerance and inter-specific hybridization have been subjected to detailed
      genetic analysis. However, the full potential for exploring the causes and
      consequences of natural variation in complex traits within the genus Arabidopsis
      has not been widely appreciated or realized. Here, we draw on broadly dispersed
      information to characterize the basic biology, ecology, population genetics and
      molecular evolution for these three non-model Arabidopsis species. We illustrate
      how the wealth of functional and genomic tools pioneered in A. thaliana can be
      applied to gain insights into adaptive evolution of ecologically important traits
      and genome-wide processes, such as polyploidy, speciation and reticulate
      evolution, within and among Arabidopsis species.

PMID- 16893673
TI  - Arabidopsis endogenous small RNAs: highways and byways.
AB  - Several classes of endogenous small RNAs of 20-26 nucleotides, such as microRNAs
      and small interfering (si)RNAs, have been described in plants and animals.
      Arabidopsis currently seems to be an exception because a novel genetically
      distinguishable small RNA class, termed natural-antisense transcript derived
      siRNAs, was recently identified. Pathways for the biogenesis and function of each
      class are already well characterized, enabling their classification on the basis
      of both size and proteins required for their function. However, each pathway
      requires proteins belonging to conserved protein families, and recent genetic
      studies confirmed an expected partial redundancy between members of the Dicer
      like (DCL) family. Moreover, several experimental results indicate redundancies
      among double-strand RNA binding proteins and ARGONAUTE proteins, which probably
      create a complex network of small RNA pathways.

PMID- 16893676
TI  - Effects of repeated praziquantel treatment on schistosomiasis mekongi morbidity
      as detected by ultrasonography.
AB  - Schistosomiasis mekongi is endemic in the Mekong River basin; about 80,000 people
      are at risk of infection in Cambodia. We conducted ultrasonographic studies of
      patients with schistosomiasis mekongi in Kratie province, Cambodia, focusing
      especially on the relationship between the frequency of praziquantel treatment
      and findings of ultrasonographic imaging. The frequency of praziquantel treatment
      in the period from 1995 to 2002 was classified into four groups: 1-2, 3-4, 5-6,
      and 7-8 times. Ultrasonographic images were examined to determine the presence of
      thickening of the portal vein wall and formation of meandering collateral
      circulation of the splenic vein. We selected these parameters because they are
      unaffected by interobserver bias. The results showed that thickening of the
      portal vein wall may have potential to improve with frequent praziquantel
      treatment. On the other hand, established hard splenomegaly and meandering
      collateral circulation of the splenic vein, improved very little with
      praziquantel treatment.

PMID- 16893675
TI  - FANCD2 monoubiquitination and activation by hexavalent chromium [Cr(VI)]
      exposure: activation is not required for repair of Cr(VI)-induced DSBs.
AB  - Fanconi anemia (FA) is a rare autosomal recessive disorder characterized by
      congenital abnormalities, progressive bone marrow failure, and cancer
      susceptibility. FA cells are hypersensitive to DNA crosslinking agents. FA is a
      genetically heterogeneous disease with at least 11 complementation groups. The
      eight cloned FA proteins interact in a common pathway with established DNA-damage
      response proteins, including BRCA1 and ATM. Six FA proteins (A, C, E, F, G, and
      L) regulate the monoubiquitination of FANCD2 after DNA damage by crosslinking
      agents, which targets FANCD2 to BRCA1 nuclear foci containing BRCA2 (FANCD1) and
      RAD51. Some forms of hexavalent chromium [Cr(VI)] are implicated as respiratory
      carcinogens and induce several types of DNA lesions, including DNA interstrand
      crosslinks. We have shown that FA-A fibroblasts are hypersensitive to both Cr(VI)
      induced apoptosis and clonogenic lethality. Here we show that Cr(VI) treatment
      induced monoubiquitination of FANCD2 in normal human fibroblasts, providing the
      first molecular evidence of Cr(VI)-induced activation of the FA pathway. FA-A
      fibroblasts demonstrated no FANCD2 monoubiquitination, in keeping with the
      requirement of FA-A for this modification. We also found that Cr(VI) treatment
      induced significantly more S-phase-dependent DNA double strand breaks (DSBs), as
      measured by gamma-H2AX expression, in FA-A fibroblasts compared to normal cells.
      However, and notably, DSBs were repaired equally in both normal and FA-A
      fibroblasts during recovery from Cr(VI) treatment. While previous research on FA
      has defined the genetic causes of this disease, it is critical in terms of
      individual risk assessment to address how cells from FA patients respond to
      genotoxic insult.

PMID- 16893677
TI  - What factors are associated with the integration of evidence retrieval technology
      into routine general practice settings?
AB  - BACKGROUND: Information retrieval systems have the potential to improve patient
      care but little is known about the variables which influence clinicians' uptake
      and use of systems in routine work. AIM: To determine which factors influenced
      use of an online evidence retrieval system. DESIGN OF STUDY: Computer logs and
      pre- and post-system survey analysis of a 4-week clinical trial of the Quick
      Clinical online evidence system involving 227 general practitioners across
      Australia. RESULTS: Online evidence use was not linked to general practice
      training or clinical experience but female clinicians conducted more searches
      than their male counterparts (mean use=14.38 searches, S.D.=11.68 versus mean
      use=8.50 searches, S.D.=9.99; t=2.67, d.f.=157, P=0.008). Practice
      characteristics such as hours worked, type and geographic location of clinic were
      not associated with search activity. Information seeking was also not related to
      participants' perceived information needs, computer skills, training nor Internet
      connection speed. Clinicians who reported direct improvements in patient care as
      a result of system use had significantly higher rates of system use than other
      users (mean use=12.55 searches, S.D.=13.18 versus mean use=8.15 searches,
      S.D.=9.18; t=2.322, d.f.=154 P=0.022). Comparison of participants' views pre- and
      post- the trial, showed that post-trial clinicians expressed more positive views
      about searching for information during a consultation (chi(2)=27.40, d.f.=4, P<
      or =0.001) and a significantly greater number reported seeking information
      between consultations as a result of having access to an online evidence system
      in their consulting rooms (chi(2)=9.818, d.f.=2, P=0.010). CONCLUSION:
      Clinicians' use of an online evidence system was directly related to their
      reported experiences of improvements in patient care. Post-trial clinicians
      positively changed their views about having time to search for information and
      pursued more questions during clinic hours.

PMID- 16893678
TI  - Quantitative analysis of HBsAg, IgM anti-HBc and anti-HBc avidity in acute and
      chronic hepatitis B.
AB  - BACKGROUND AND OBJECTIVES: We evaluated hepatitis B virus (HBV) serological
      markers by novel, quantitative immunoassays in order to study their behaviours
      and possible role in the various phases of HBV infection. STUDY DESIGN: The
      quantitative determination of HBsAg and anti-HBc/IgM by chemiluminescent
      immunoassays (Abbott Architect) and the calculation of anti-HBc avidity index
      have been carried out on repository specimens from patients with acute or chronic
      hepatitis B. RESULTS: In acute hepatitis the levels of HBsAg were generally
      >10,000 UI/mL and decreased sharply in the recovery phase. In 35 anti-HBe
      positive chronic hepatitis cases HBsAg levels were generally lower than 10,000
      UI/mL (mean: 2655), whereas in five HBeAg-positive chronic hepatitis patients the
      mean value was 78,756 UI/mL and 90% of specimens exceeded 10,000 UI/mL. The
      lowest values (mean: 1029 IU/mL) were found in the seven patients with minimal
      hepatic damage. IgM anti-HBc antibodies were positive in all acute cases and in
      68/207 samples (32.85%) from patients with chronic hepatitis, with significantly
      lower levels (average sample/cutoff (S/CO) ratio: 2.95 in chronic cases versus
      25.96 in acute cases; p<0.005). A S/CO value of 10 for anti-HBc IgM had a 100%
      negative predictive value and a 99.13% positive predictive value for acute
      hepatitis B. The study of anti-HBc avidity by an experimental procedure showed
      that an avidity index (AI) threshold of 0.7 had a good efficacy to discriminate
      the cases of chronic hepatitis, among whom only 2 specimens out of 193 (1.04%)
      had an AI<0.7. CONCLUSION: The quantitative determination of HBsAg, anti-HBc/IgM
      and anti-HBc avidity provides additional information and may be useful in the
      differential diagnosis of acute and chronic HBV infections and in the follow-up
      of chronically infected patients.

PMID- 16893679
TI  - On the dual structure of the auditory brainstem response in dogs.
AB  - OBJECTIVE: To use the over-complete discrete wavelet transform (OCDWT) to further
      examine the dual structure of auditory brainstem response (ABR) in the dog.
      METHODS: ABR waveforms recorded from 20 adult dogs at supra-threshold (90 and
      70dBnHL) and threshold (0-15dBSL) levels were decomposed using a six level OCDWT
      and reconstructed at individual scales (frequency ranges) A6 (0-391Hz), D6 (391
      781Hz), and D5 (781-1563Hz). RESULTS: At supra-threshold stimulus levels, the A6
      scale (0-391Hz) showed a large amplitude waveform with its prominent wave
      corresponding in latency with ABR waves II/III; the D6 scale (391-781Hz) showed a
      small amplitude waveform with its first four waves corresponding in latency to
      ABR waves I, II/III, V, and VI; and the D5 scale (781-1563Hz) showed a large
      amplitude, multiple peaked waveform with its first six waves corresponding in
      latency to ABR waves I, II, III, IV, V, and VI. At threshold stimulus levels (0
      15dBSL), the A6 scale (0-391Hz) continued to show a relatively large amplitude
      waveform, but both the D6 and D5 scales (391-781 and 781-1563Hz, respectively)
      now showed relatively small amplitude waveforms. CONCLUSIONS: A dual structure
      exists within the ABR of the dog, but its relative structure changes with
      stimulus level. SIGNIFICANCE: The ABR in the dog differs from that in the human
      both in the relative contributions made by its different frequency components,
      and the way these components change with stimulus level.

PMID- 16893680
TI  - Automated localization of magnetoencephalographic interictal spikes by adaptive
      spatial filtering.
AB  - OBJECTIVE: Automated adaptive spatial filtering techniques can be applied to
      magnetoencephalographic (MEG) data collected from people with epilepsy. Source
      waveforms estimated by these methods have higher signal-to-noise ratio (SNR) than
      spontaneous MEG data, allowing identification and location of interictal spikes.
      The software tool SAM(g(2)) provides an adaptive spatial filtering algorithm for
      MEG data that yields source images of excess kurtosis and provides source time
      courses in voxels exhibiting high excess kurtosis. The sensitivity and
      specificity of SAM(g(2)) in epilepsy is unknown. METHODS: Interictal MEG data
      from 36 patients with intractable epilepsy were analyzed using SAM(g(2)), and
      results compared with equivalent current dipole (ECD) fit procedures. RESULTS:
      When SNR of interictal spikes was high (compared to background) with a clear
      single focus, in most cases there was good agreement between ECD and SAM(g(2)).
      With multiple foci, there was typically overlap but imperfect concordance between
      results of ECD and SAM(g(2)). CONCLUSIONS: SAM(g(2)) may in some cases be
      equivalent to manual ECD fit for localizing interictal spikes with single locus
      and good SNR. Further studies are required to validate SAM(g(2)) with multiple
      foci or poor SNR. SIGNIFICANCE: In some cases, SAM(g(2)) might eventually assist
      or replace manual ECD analysis of MEG data.

PMID- 16893682
TI  - The acid-induced operon Rv3083-Rv3089 is required for growth of Mycobacterium
      tuberculosis in macrophages.
AB  - The Rv3083-Rv3089 operon of Mycobacterium tuberculosis has been shown to be
      induced 17-33-fold when tubercle bacilli were exposed in vitro to acidic
      conditions which may mimic those that the bacilli encounter early during the
      infection and it is induced during growth in macrophages. To understand the role
      of this operon in intracellular survival, we constructed a knockout of the operon
      in the M. tuberculosis H37Rv strain. No differences were observed in the growth
      of mutant and wild-type mycobacteria on axenic media. Though the uptake of mutant
      and wild-type bacteria by eukaryotic cells was similar, the mutant failed to grow
      subsequently. By 192h post-infection, the fold differences between the wild-type
      and mutant bacteria were significant thus leading to the conclusion that the
      mutant is defective for intracellular growth in these cell lines. Complementation
      of the knockout restored intracellular growth to wild-type levels. During the
      first 24-48h post-infection, mutant bacteria also stimulated production of
      significantly less IL-1beta, IL-6, IL-8, RANTES, and MCP-1 by THP-1 cells than
      wild-type bacteria. Overall, the data indicate that the operon plays an important
      role in the ability of M. tuberculosis to grow inside host cells.

PMID- 16893681
TI  - Optical properties of porphyrin molecules immobilized in nano-porous silicon.
AB  - The paper aims at studying optical properties of porous silicon powders and thin
      films which were impregnated with different porphyrin molecules. It has been
      shown that introducing porphyrins into porous silicon matrix results in quenching
      of luminescence from porous silicon, while luminescence of porphyrins survives,
      though its structure changes. At the same time, porphyrins in porous silicon
      matrix which was preliminarily oxidized does not alter luminescence from
      porphyrins. Generation of singlet oxygen by illuminated porphyrin/porous silicon
      composite is confirmed by additional oxidation of porous silicon and by the
      observation of characteristic 1270 nm luminescence band.

PMID- 16893683
TI  - A review on infection with human immunodeficiency virus.
AB  - Management of infection with human immunodeficiency virus (HIV) improved
      dramatically during the 1990s. The advent of high-performance quantitative HIV
      assays and highly active antiretroviral therapy were the two most important
      developments in HIV medicine. As a result, HIV mortality and morbidity have
      reduced significantly, although a proportion of HIV-infected patients are still
      diagnosed late. Management of HIV during pregnancy has also improved so that
      vertical transmission is now limited to less than 2% of all cases. Knowledge of
      the different stages of HIV infection enables optimal timing of start of
      antiretroviral therapy. Routine offering of HIV testing might also reduce the
      number of patients diagnosed with immunodeficiency. Better knowledge of the life
      cycle of HIV has made it possible to design new classes of antiretroviral drugs.
      The new drugs, however, pose new challenges as they might have long-term side
      effects. In addition, their interactions with other antiretroviral drugs might
      not be favourable.

PMID- 16893684
TI  - In vivo gene transfer into adult stem cells in unconditioned mice by in situ
      delivery of a lentiviral vector.
AB  - The potential of in vivo lentivirus-mediated bone marrow stem cell gene transfer
      by bone cavity injection, which could take full advantage of any source of stem
      cells present there, has not been previously explored. Such an approach may avoid
      several difficulties encountered by ex vivo hematopoietic stem cell (HSC) gene
      transfer. We sought to determine if efficient gene transfer could be achieved in
      HSC and mesenchymal stem/progenitor cells (MSC) by intrafemoral injection of a
      lentivirus vector in mice. Four months after injection, up to 12% GFP-expressing
      cells were observed in myeloid and lymphoid subpopulations. Significant
      transduction efficiencies were seen in Lin(-)c-kit(+)Sca1(+) HSC/progenitors and
      CFU with multilineage potential, which were also confirmed by duplex PCR analysis
      of progenitor-derived colonies. Four months after secondary BMT, we observed 8.1
      to 15% vector(+) CFU in all recipients. Integration analysis by LAM-PCR
      demonstrated that multiple transduced clones contributed to hematopoiesis in
      these animals. We also showed that GFP-expressing MSC retained multilineage
      differentiation potential, with 2.9 to 8.8% GFP-containing CFU-fibroblasts
      detected in both injected and BMT recipients. Our data provide evidence that
      adult stem cells in bone marrow can be efficiently transduced "in situ" by in
      vivo vector administration without preconditioning. This approach could lead to a
      novel application for treatment of human diseases.

PMID- 16893685
TI  - Chromatin structural elements and chromosomal translocations in leukemia.
AB  - Recurring chromosome abnormalities are strongly associated with certain subtypes
      of leukemia, lymphoma and sarcomas. More recently, their potential involvement in
      carcinomas, i.e. prostate cancer, has been recognized. They are among the most
      important factors in determining disease prognosis, and in many cases,
      identification of these chromosome abnormalities is crucial in selecting
      appropriate treatment protocols. Chromosome translocations are frequently
      observed in both de novo and therapy-related acute myeloid leukemia (AML) and
      myelodysplastic syndromes (MDS). The mechanisms that result in such chromosome
      translocations in leukemia and other cancers are largely unknown. Genomic
      breakpoints in all the common chromosome translocations in leukemia, including
      t(4;11), t(9;11), t(8;21), inv(16), t(15;17), t(12;21), t(1;19) and t(9;22), have
      been cloned. Genomic breakpoints tend to cluster in certain intronic regions of
      the relevant genes including MLL, AF4, AF9, AML1, ETO, CBFB, MYHI1, PML, RARA,
      TEL, E2A, PBX1, BCR and ABL. However, whereas the genomic breakpoints in MLL tend
      to cluster in the 5' portion of the 8.3 kb breakpoint cluster region (BCR) in de
      novo and adult patients and in the 3' portion in infant leukemia patients and t
      AML patients, those in both the AML1 and ETO genes occur in the same clustered
      regions in both de novo and t-AML patients. These differences may reflect
      differences in the mechanisms involved in the formation of the translocations.
      Specific chromatin structural elements, such as in vivo topoisomerase II (topo
      II) cleavage sites, DNase I hypersensitive sites and scaffold attachment regions
      (SARs) have been mapped in the breakpoint regions of the relevant genes. Strong
      in vivo topo II cleavage sites and DNase I hypersensitive sites often co-localize
      with each other and also with many of the BCRs in most of these genes, whereas
      SARs are associated with BCRs in MLL, AF4, AF9, AML1, ETO and ABL, but not in the
      BCR gene. In addition, the BCRs in MLL, AML1 and ETO have the lowest free energy
      level for unwinding double strand DNA. Virtually all chromosome translocations in
      leukemia that have been analyzed to date show no consistent homologous sequences
      at the breakpoints, whereas a strong non-homologous end joining (NHEJ) repair
      signature exists at all of these chromosome translocation breakpoint junctions;
      this includes small deletions and duplications in each breakpoint, and micro
      homologies and non-template insertions at genomic junctions of each chromosome
      translocation. Surprisingly, the size of these deletions and duplications in the
      same translocation is much larger in de novo leukemia than in therapy-related
      leukemia. We propose a non-homologous chromosome recombination model as one of
      the mechanisms that results in chromosome translocations in leukemia. The topo II
      cleavage sites at open chromatin regions (DNase I hypersensitive sites), SARs or
      the regions with low energy level are vulnerable to certain genotoxic or other
      agents and become the initial breakage sites, which are followed by an excision
      end joining repair process.

PMID- 16893686
TI  - Antibody production: polyclonal-derived biotherapeutics.
AB  - Antibody based therapies using monoclonal or polyclonal antibodies are emerging
      as an important therapeutic approach for the treatment of a number of diseases.
      With increasing emphasis on new technologies associated with monoclonal antibody
      expression and purification, the clinical need of polyclonal therapeutics for
      treatment of a variety of specific illnesses and infections is often overlooked.
      Despite being largely abandoned in the early twentieth century due to the
      development of antibiotics, polyclonal antibody therapeutics are today widely
      used in medicine for viral and toxin neutralization and for replacement therapy
      in patients with immunoglobulin deficiencies. Over the past 20 years, intravenous
      immunoglobulins have shown beneficial immunomodulatory and anti-inflammatory
      effects in many illnesses. Hyperimmune antibody preparations have been used over
      the past century for the treatment of a variety of infectious agents and medical
      emergencies, including digoxin toxicity, snake envenomation and spider bites.
      Here, we examine the contemporary techniques and applications, and assess the
      future therapeutic potential, for polyclonal-derived antibody therapeutics.

PMID- 16893687
TI  - Simultaneous determination of selegiline and desmethylselegiline in human body
      fluids by headspace solid-phase microextraction and gas chromatography-mass
      spectrometry.
AB  - A method for the simultaneous determination of selegiline and its metabolite,
      desmethylselegiline, in human whole blood and urine is presented. The method,
      which combines a fiber-based headspace solid-phase microextraction (SPME)
      technique with gas chromatography-mass spectrometry (GC-MS), required
      optimization of various parameters (e.g., salt additives, extraction
      temperatures, extraction times and the extraction properties of the SPME fiber
      coatings). Pargyline was used as the internal standard. Extraction efficiencies
      for both selegiline and desmethylselegiline were 2.0-3.4% for whole blood, and
      8.0-13.2% for urine. The regression equations for selegiline and
      desmethylselegiline extracted from whole blood were linear (r(2)=0.996 and 0.995)
      within the concentration ranges 0.1-10 and 0.2-20 ng/ml, respectively. For urine,
      the regression equations for selegiline and desmethylselegiline were linear
      (r(2)=0.999 and 0.998) within the concentration ranges 0.05-5.0 and 0.1-10 ng/ml,
      respectively. The limit of detection for selegiline and desmethylselegiline was
      0.01-0.05 ng/ml for both samples. The lower and upper limits of quantification
      for each compound were 0.05-0.2 and 5-20 ng/ml, respectively. Intra- and inter
      day coefficients of variation for selegiline and desmethylselegiline in both
      samples were not greater than 8.7 and 11.7%, respectively. The determination of
      selegiline and desmethylselegiline concentrations in Parkinson's disease patients
      undergoing continuous selegiline treatment is presented and is shown to validate
      the present methodology.

PMID- 16893688
TI  - Quantification of the urinary concentrations of parabens in humans by on-line
      solid phase extraction-high performance liquid chromatography-isotope dilution
      tandem mass spectrometry.
AB  - Parabens (alkyl esters of p-hydroxybenzoic acid) are widely used as antimicrobial
      preservatives in cosmetic products, pharmaceuticals, and food processing.
      However, weak estrogenicity of some parabens has been revealed from several
      studies. Human exposure to parabens may be assessed by measuring the conjugated
      or free species of these compounds or their metabolites in urine. We have
      developed a method using on-line solid phase extraction-high performance liquid
      chromatography-isotope dilution tandem mass spectrometry with peak focusing to
      measure the urinary concentrations of methyl, ethyl, propyl, n- and iso- butyl,
      and benzyl parabens. This method has good reproducibility and accuracy with
      detection limits for all analytes below 0.2ng/mL in 100microL of urine, and
      permits quick and accurate analysis of a large number of samples in epidemiologic
      studies for assessing the prevalence of human exposure to parabens. Using this
      method, we detected methyl, ethyl, and propyl parabens, mostly as conjugated
      species, in 22 urine samples collected from anonymous adults.

PMID- 16893689
TI  - Liquid chromatography with tandem mass spectrometry for the simultaneous
      determination of baicalein, baicalin, oroxylin A and wogonin in rat plasma.
AB  - A rapid, sensitive and selective liquid chromatography-tandem mass spectrometric
      (LC-MS/MS) method for the determination of baicalein, baicalin, oroxylin A and
      wogonin, Scutellaria baicalensis active components in rat plasma was developed.
      After liquid-liquid extraction with 2-(3,4-dimethoxy-phenyl)-5,7-dihydroxy
      chromen-4-one as internal standard, baicalein, baicalin, oroxylin A and wogonin
      were eluted from an Atlantis C(18) column within 7 min with isocratic mobile
      phase consisting of methanol and 0.1% formic acid (60:40, v/v). The analytes were
      detected using an electrospray ionization tandem mass spectrometry in the
      multiple reaction monitoring (MRM) mode. The standard curves were linear
      (r=1.000) over the concentration ranges of 5-500 ng/ml for baicalein, wogonin and
      oroxylin A and 5-5000 ng/ml for baicalin. The coefficients of variation and
      relative errors of baicalein, wogonin, oroxylin A and baicalin for intra- and
      inter-assay at three or four quality control (QC) levels were 0.8-6.1% and -4.0
      to 5.8%, respectively. The lower limits of quantification for baicalein, wogonin,
      oroxylin A and baicalin were 5ng/ml using 50 microl of plasma sample. This method
      was successfully applied to the pharmacokinetic study of baicalein, baicalin,
      wogonin and oroxylin A after an intravenous administration of Scutellariae radix
      extract to male Sprague-Dawley rats.

PMID- 16893690
TI  - High-performance liquid chromatographic method for the determination of histamine
      and 1-methylhistamine in biological buffers.
AB  - A method for the determination of histamine and its catabolite 1-methylhistamine
      (1-MH) was developed, using HPLC with fluorescence detection. Derivatization of
      both compounds occurred on-column with o-phthaldialdehyde dissolved in an
      alkaline borate buffer, followed by separation on a reversed phase C18 column.
      Histamine and 1-MH could be detected with comparable sensitivity (limit of
      quantification, 50 nM). The method was proven suitable to investigate catabolism
      of histamine by epithelia of pig colon. The method should be useful in research
      on histamine metabolism.

PMID- 16893691
TI  - A potential generic downstream process using Cibracon Blue resin at very high
      loading capacity produces a highly purified monoclonal antibody preparation from
      cell culture harvest.
AB  - The use of a dye-ligand chromatography for the purification of monoclonal
      antibody (MAb) from cell culture and other feed streams has been largely
      overlooked in large scale production. Cibracon Blue dye (CB), a polycyclic
      anionic ligand, interacts with protein through a specific interaction between the
      dye, acting as a mimic of NAD+ and NADP+, or through non-specific electrostatic,
      hydrophobic, and other forces. In this paper, a CB resin was used to effectively
      and efficiently separate an IgG4 MAb from host and process impurities following
      the capture of the MAb on a Protein-A (PA) column. The CB unit operation,
      challenged at </=180 g MAb/L of resin with the PA eluate, reduced BSA (1-2 log),
      host cell protein (HCP; 2-3 log), MAb oligomer (31-85%), fragment (from
      approximately 0.8% to <0.1%), and other undesired MAb species. Purity, as
      measured by non-reducing (NR) SDS-PAGE, was improved 33-85%, to 92-99.5% overall
      (>99% by reducing SDS-PAGE). A facile three column scalable production scheme,
      employing CB as the second column in the process was used to generate highly
      purified MAb from cell culture harvest derived from two media of very different
      compositions. Free CB dye was </=1 ng/mg in MAb preparations purified through the
      three column process and then concentrated and buffer exchanged into the
      appropriate buffer using tangential flow filtration (TFF).

PMID- 16893692
TI  - Intravascular ultrasound profile analysis of ruptured coronary plaques.
AB  - Angiographic studies have shown that lesions preceding nonfatal acute events are
      usually not hemodynamically significant. This has led to the concept that plaque
      ruptures occur at minimal disease sites. We used intravascular ultrasound to
      create a prerupture "profile" of unstable (vulnerable) plaques. We analyzed 112
      ruptured plaques detected by intravascular ultrasound. Reference and lesion
      external elastic membrane (EEM) and lumen areas were measured to calculate
      prerupture estimates of plaque area, plaque burden (plaque/EEM area),
      eccentricity, area stenosis, and remodeling. The narrowest coefficients of
      variance were for lesion EEM area, maximum plaque thickness, and plaque burden,
      reference lumen area, and remodeling index (coefficients of variance 0.29, 0.25,
      0.12, 0.29, and 0.18, respectively); conversely, there was great variability in
      measurements of calcification and lumen compromise (minimum lumen area and area
      stenosis). When using the 5 variables with the narrowest coefficient of variance,
      we found that 67% of ruptured plaques fit all of following 10th or 90th
      percentile parameters (> 14.3 mm2 lesion EEM area, > 8.1 mm2 reference lumen
      area, > 1.6 mm maximum lesion plaque thickness, > 0.63 lesion plaque burden, and
      > 0.87 remodeling index). Further, 89% of ruptured plaques fit 4 of 5 parameters
      and 96% fit 3 of 5 parameters. In conclusion, plaque ruptures do not occur at
      minimal disease sites. Rather, vulnerable (rupture-prone) plaques predictably
      have significant plaque accumulation and remodeling and occur in larger arteries.
      It is only the degree of lumen compromise that is variable and often
      insignificant.

PMID- 16893693
TI  - Outcome after acute incomplete sirolimus-eluting stent apposition as assessed by
      serial intravascular ultrasound.
AB  - We investigated the fate of postprocedural incomplete stent apposition (ISA)
      after sirolimus-eluting stent (SES) implantation by evaluating long-term
      intravascular ultrasound findings in 168 consecutive patients (182 de novo
      lesions). Postprocedural ISA was defined as > or = 1 stent strut that was clearly
      separated from the vessel wall with evidence of blood speckle behind the strut
      without overlapping a side branch. After SES implantation, there were 61 ISA
      sites in 46 stents in 31 patients (23 at the proximal edge, 7 at the distal edge,
      and 31 within the stent body). There were no clinical, procedural, or
      intravascular ultrasound measurement differences between patients and lesions
      with versus without ISA. At follow-up, 15 acute ISA sites (25%) in 11 patients
      completely resolved and 40 sites (75%) in 20 patients persisted, although 32 of
      46 persisting ISA sites (70%) decreased. There was a greater decrease in
      effective lumen area and a greater increase in peristent plaque area in the
      complete-resolution group than in the persistent-ISA group. No lesion developed
      stent thrombosis or in-stent restenosis (angiographic diameter stenosis > 50%).
      Six acute ISA sites were also associated with new, late acquired ISA, only 1 of
      which resulted in aneurysm formation. Although most ISAs after SES implantation
      do not resolve completely, the incidence of restenosis or thrombosis is not
      affected.

PMID- 16893694
TI  - Angiographic results of the first human experience with the Biolimus A9 drug
      eluting stent for de novo coronary lesions.
AB  - This report describes angiographic findings of the first-in-human evaluation of
      the Biolimus A9 drug-eluting stent (Biolimus stent) in the treatment of
      noncomplex coronary lesions. In total, 120 patients with 122 de novo coronary
      lesions (2.75- to 4.00-mm vessels, < or = 24-mm lesion length) were prospectively
      randomized in a 2:1 ratio to receive the Biolimus stent (n = 80, 82 lesions) or
      the control uncoated stent (n = 40). Baseline lesion and angiographic
      characteristics were similar between groups. At 6-month follow-up, late lumen
      loss was significantly decreased with the Biolimus stent in the stent (0.26 +/-
      0.43 vs 0.74 +/- 0.45 mm, p < 0.001) and in the segment (0.14 +/- 0.45 vs 0.40 +/
      0.41 mm, p = 0.004). In-stent restenosis was 3.9% in the Biolimus stent group
      versus 7.7% in the control group (p = 0.40). There was no exaggerated hyperplasia
      at the proximal and/or distal edge of the stent.

PMID- 16893695
TI  - Outcome of percutaneous coronary intervention in unstable angina pectoris versus
      stable angina pectoris in two different time periods.
AB  - Percutaneous coronary intervention (PCI) for unstable angina pectoris (UAP) has
      traditionally been associated with a higher risk of ischemic complications than
      that for stable angina pectoris (SAP). However, PCI procedures have evolved, so
      this study was designed to determine whether PCI for UAP is still associated with
      less favorable outcomes. In-hospital and 1-year outcomes in Dynamic Registry
      patients who presented for PCI with UAP (n = 2,994) or SAP (n = 1,457) between
      1997 and 2002 were compared. One-year results were also compared with consecutive
      patients who underwent angioplasty (n = 2,431) from the 1985 to 1986 Percutaneous
      Transluminal Coronary Angioplasty Registry. Although Dynamic Registry patients
      with UAP were older and more likely to smoke (p < 0.05), have diabetes mellitus
      (p = 0.03), or a previous myocardial infarction (p < 0.001), procedural success
      was higher than in patients with SAP. By 1 year, there was greater risk of death
      (4.4% vs 2.6%, p < 0.01), death/myocardial infarction (9.9% vs 6.6%, p < 0.001),
      and death, myocardial infarction, and coronary artery bypass grafting (15.1% vs
      11.6%, p < 0.01) in patients with UAP. In patients with UAP, there was no
      significant difference in adjusted 1-year death and death/myocardial infarction
      rates when comparing the waves of the Dynamic Registry with those of the
      Percutaneous Transluminal Coronary Angioplasty Registry, although
      death/myocardial infarction rates among Dynamic Registry patients were lower.
      However, in patients with SAP, the adjusted rate for death/myocardial infarction
      was lower in wave 3, and for death, myocardial infarction, and revascularization,
      there was a significant decrease in event rates with each successive recruitment
      period (p < 0.05 for all comparisons). In conclusion, in contradistinction to
      patients with SAP, death and death/myocardial infarction rates in patients who
      have undergone PCI for UAP have not significantly decreased over the past 16
      years and patients with UAP remain at a greater risk of ischemic events at 1 year
      compared with patients with SAP.

PMID- 16893696
TI  - Usefulness of plasma brain natriuretic peptide concentration for predicting
      subsequent left ventricular remodeling after coronary angioplasty in patients
      with acute myocardial infarction.
AB  - To determine the relation between plasma brain natriuretic peptide (BNP) and
      remodeling in terms of infarct-related artery (IRA) patency, 106 patients with a
      first anterior wall acute myocardial infarction with a patent IRA at 1 month were
      studied. The IRA reoccluded at 6 months in 17 patients (reoccluded IRA) and was
      patent in 89 patients (patent IRA). The 2 groups did not differ with respect to
      clinical characteristics, hemodynamic variables, and left ventricular function at
      1 month, except for left ventricular end-diastolic and systolic volumes, which
      were significantly greater in the reoccluded IRA group. Plasma BNP concentration
      in the reoccluded IRA group (336 +/- 288 pg/ml) was significantly higher than
      that in the patent IRA group (116 +/- 106 pg/ml) at 1 month. BNP concentration
      decreased significantly at 6 months in the 2 groups (reoccluded IRA vs patent IRA
      152 +/- 162 vs 44 +/- 58 pg/ml, p <0.05). The increase in left ventricular volume
      from 1 to 6 months was significantly correlated with plasma BNP concentration at
      1 month in the patent IRA group (r = 0.314, p < 0.01) and the reoccluded group (r
      = 0.634, p < 0.01). Linear regression analysis showed that the correlation
      between the 2 parameters in the 2 groups was similar. Based on stepwise
      multivariate linear regression analysis, only plasma BNP concentration was
      significantly correlated with the increase in left ventricular volume from 1 to 6
      months in the 2 groups. In conclusion, these results suggest that plasma BNP
      concentration predicts left ventricular dilation independently of IRA patency.

PMID- 16893698
TI  - Effect of everolimus-eluting stents in different vessel sizes (from the pooled
      FUTURE I and II trials).
AB  - The everolimus-eluting stent (EES) has been shown to significantly decrease
      neointimal proliferation at 6 months compared with the bare metal stent (BMS) in
      patients with de novo coronary lesions. We report mid-term outcomes based on
      different vessel sizes in the combined FUTURE I and II trials. In the
      prospective, randomized, FUTURE I trial (single center) and expanded FUTURE II
      trial (multicenter), 106 patients (107 lesions) were randomized to EESs (n = 49
      lesions) or BMSs (n = 58 lesions). Patients were categorized into 3 groups based
      on preprocedure reference diameter as assessed by quantitative coronary
      angiography (small vessel < 2.75 mm, medium vessel 2.75 to 3.25 mm, and large
      vessel > 3.25 mm). At 6-month follow-up, EESs decreased in-stent late lumen loss
      (decreased rate range of 78% to 94%), resulting in significantly larger minimum
      lumen area as assessed by intravascular ultrasound (increased range of 34% to
      42%) compared with the BMS across all vessel sizes. There were no cases of in
      stent restenosis with EESs at any vessel size but 8 cases with BMSs (5 in small
      vessels). No stent thrombosis, aneurysm formation, or late stent incomplete
      apposition was observed in any group. The EES appears to be effective for
      treatment of de novo coronary lesions in decreasing neointimal proliferation at 6
      month follow-up compared with BMSs, regardless of vessel size.

PMID- 16893697
TI  - Frequency and outcomes of acute renal failure following thoracic aortic stent
      graft placement.
AB  - We assessed the incidence, correlates, and outcomes of acute renal failure (ARF)
      after thoracic aortic stent-graft placement. Postprocedural ARF is an inherent
      complication of catheter-based interventional procedures that use intra-arterial
      contrast agents and has adverse effects on short- and long-term outcomes.
      However, few data exist on the incidence, predictors, and outcomes of ARF after
      thoracic aortic stent-graft placement. We analyzed data of 97 patients (64.4 +/-
      11.6 years of age; 73% men) who underwent thoracic aortic stent-graft placement
      from July 1999 to October 2005. Postprocedural ARF was defined as an increase >
      or = 25% and/or > or = 0.5 mg/dl in preprocedural serum creatinine at 48 hours
      after the procedure. Baseline estimated glomerular filtration rate was 65 +/- 24
      ml/min/1.73 m2. Chronic kidney disease (glomerular filtration rate < or = 60
      ml/min/1.73 m2) at baseline was present in 45% of patients. During the stent
      graft procedure, patients received 307 +/- 188 ml of nonionic contrast medium.
      Postprocedural ARF occurred in 33 patients (34%), and 3 required dialysis.
      Multivariable analysis identified American Society of Anesthesiologists class > 3
      (odds ratio 5.53, 95% confidence interval 1.71 to 17.85, p = 0.004) and duration
      of the stent-graft procedure (odds ratio 1.01, 95% confidence interval 1.001 to
      1.014, p = 0.022) as independent predictors of postprocedural ARF. Compared with
      patients without ARF, those with ARF had markedly higher 30-day (18.2 +/- 6.7% vs
      1.6 +/- 1.6%, p = 0.0022) and 1-year (35.2 +/- 8.6% vs 10.1 +/- 3.9%, p = 0.001)
      mortality. In conclusion, postprocedural ARF is a frequent complication of
      thoracic aortic stent-graft placement and has a significant adverse effect on 30
      day and 1-year survival. Baseline factors identified in our study as associated
      with increased risk of ARF may facilitate a comprehensive informed consent
      process by way of patient education. In addition, identification of an at-risk
      subset may allow modification of reversible periprocedural factors that may help
      decrease postprocedural ARF.

PMID- 16893699
TI  - Prognostic significance of admission heart failure in patients with non-ST
      elevation acute coronary syndromes (from the Canadian Acute Coronary Syndrome
      Registries).
AB  - We evaluated the in-hospital and 1-year outcomes and predictors of admission
      heart failure in patients with non-ST-elevation acute coronary syndromes (NSTE
      ACSs) without previous heart failure. We analyzed 4,825 patients with NSTE-ACS
      without a history of congestive heart failure who were included in the
      multicenter Canadian ACS Registries. Patients in Killip's class II/III on
      admission (n = 559, 11.6%) were compared with patients in Killip's class I.
      Patients with heart failure on admission were older (72 [64, 79] vs 64 [54, 73]
      years, p < 0.0001), with higher baseline creatinine levels (96 vs 88 mmol/dl, p
      <0.0001), more diabetes (32.2% vs 22.8%, p < 0.0001), hypertension (58% vs 52.4%,
      p = 0.014), previous myocardial infarction (MI; 38.9% vs 30.3%, p < 0.0001),
      previous stroke (13.5% vs 7.4%, p < 0.0001), and had more ST depression on
      admission (27.7% vs 17.3%, p < 0.0001). In-hospital treatment was similar except
      for a lower rate of aspirin therapy and fewer coronary interventions. Crude event
      rates were significantly higher in patients with heart failure (in-hospital death
      3.6% vs 1.1%, p < 0.0001; death or MI 7.9% vs 4.7%, p = 0.0011; stroke 1.1% vs
      0.4%, p = 0.03). One-year event rates were also higher in patients with heart
      failure (death 14.6% vs 4.4%, p < 0.0001; MI 9.3% vs 6.6%, p = 0.03; death or MI
      21.5% vs 10.3%, p < 0.0001). Variables independently associated with heart
      failure were age (odds ratio 1.57, 95% confidence interval 1.43 to 1.73),
      diabetes mellitus (odds ratio 1.53, 95% confidence interval 1.24 to 1.89),
      admission ST depression (odds ratio 1.52, 95% confidence interval 1.22 to 1.90),
      previous MI, and baseline creatinine. Heart failure on admission was an
      independent predictor of in-hospital death, death or MI, and stroke and of 1-year
      death and death or MI. In conclusion, in patients with NSTE-ACS, heart failure on
      admission is associated with increased short- and long-term rates of death and
      MI.

PMID- 16893700
TI  - Relation between body mass index and clinical outcome in acute myocardial
      infarction.
AB  - Obesity has long been identified as a risk factor for coronary artery disease.
      However, the data evaluating outcomes in patients with acute myocardial
      infarction (AMI) related to body mass index (BMI) are limited and inconsistent.
      Patients (n = 284) who were diagnosed with AMI at the Medical College of Georgia
      from January 1, 2003 to June 25, 2004, were included in this retrospective
      analysis. BMI, risk for factors for coronary artery disease, AMI characteristics,
      and outcome variables were obtained from chart records. Logistic and multiple
      regression techniques were used to model and test hypotheses regarding the effect
      on outcomes after AMI, adjusting for cardiac risk factors, demographics, and
      other contextual variables. Compared with normal weight patients, underweight
      patients had more (65% vs 40%) and morbidly obese patients had fewer (21% vs 40%)
      ST-elevation AMIs (p = 0.014). Among all patients with AMIs, morbidly obese
      patients tended to be younger than normal weight subjects. No adverse relations
      among BMI and mortality, length of stay, readmission rates, or revascularzation
      in AMI were identified in this analysis. Both diabetes and previous aspirin use
      were found to increase the odds of in-hosptial mortality during AMI independent
      of BMI. In conclusion, despite the association between obesity and development of
      coronary artery disease, obesity does not adversely impact in-hospital outcomes
      in AMI. However, obesity is associated with AMI at a younger age.

PMID- 16893701
TI  - Marijuana use, diet, body mass index, and cardiovascular risk factors (from the
      CARDIA study).
AB  - Marijuana use has been associated with increased appetite, high caloric diet,
      acute increase in blood pressure, and decreases in high-density lipoprotein
      cholesterol and triglycerides. Marijuana is the most commonly used illicit drug
      in the United States, but its long-term effects on body mass index (BMI) and
      cardiovascular risk factors are unknown. Using 15 years of longitudinal data from
      3,617 black and white young adults participating in the Coronary Artery Risk
      Development in Young Adults (CARDIA) study, we assessed whether marijuana use was
      associated with caloric intake, BMI, and cardiovascular risk factors. Of the
      3,617 participants, 1,365 (38%) reported ever using marijuana. Marijuana use was
      associated with male gender, tobacco smoking, and other illicit drug use. More
      extensive marijuana use was associated with a higher caloric intake (2,746
      kcal/day in never users to 3,365 kcal/day in those who used marijuana for > or =
      1,800 days over 15 years) and alcohol intake (3.6 to 10.8 drinks/week), systolic
      blood pressure (112.7 to 116.5 mm Hg), and triglyceride levels (84 to 100 mg/dl
      or 0.95 to 1.13 mmol/L, all p values for trend < 0.001), but not with higher BMI
      and lipid and glucose levels. In multivariate analysis, the associations between
      marijuana use and systolic blood pressure and triglycerides disappeared, having
      been mainly confounded by greater alcohol use in marijuana users. In conclusion,
      although marijuana use was not independently associated with cardiovascular risk
      factors, it was associated with other unhealthy behaviors, such as high caloric
      diet, tobacco smoking, and other illicit drug use, which all have long-term
      detrimental effects on health.

PMID- 16893703
TI  - Fetal cardiac repolarization abnormalities.
AB  - Abnormal cardiac repolarization renders the heart susceptible to lethal
      ventricular tachyarrhythmias, increasing the risk of sudden cardiac death in all
      ages; however, little is known about the incidence and etiology of T-wave
      abnormalities in utero. In this study, magnetocardiography was used to better
      define fetal T-wave characteristics, including the QT interval in the normal
      fetus, and to characterize T-wave abnormalities in the fetus with arrhythmia. The
      QT interval and T-wave alternans were assessed from magnetocardiographic
      recordings obtained at 14 to 39 weeks' gestation from 120 fetuses. Of these
      fetuses, 78 were from uncomplicated pregnancies and 42 had various forms of fetal
      arrhythmia (supraventricular tachycardia in 14, congenital atrioventricular block
      in 17, long QT syndrome with Torsades de pointes in 1, ventricular tachycardia in
      2, sinus bradycardia in 4, and bradycardia due to blocked premature atrial
      contractions in 4). Although the corrected QT interval in normal sinus rhythm was
      accurately described by Bazett's formula, the corrected QT interval in fetal
      arrhythmia exhibited a systematic deviation at heart rate extremes. The
      dependence of the QT interval on the RR interval in arrhythmia was approximately
      described by QT alpha RR0.8. T-wave alternans was detected in 7 fetuses with
      arrhythmia, often in association with QT prolongation, suboptimal outcome, or
      fetal demise. The results of our study have demonstrated that QT-interval
      abnormalities exist and can be detected in fetal patients. The potential
      importance of T-wave assessment in the fetus with cardiac arrhythmia was
      evidenced by the high incidence of marked QT prolongation and T-wave alternans in
      the fetuses with suboptimal outcomes.

PMID- 16893702
TI  - Relations among renal function, risk of sudden cardiac death, and benefit of the
      implanted cardiac defibrillator in patients with ischemic left ventricular
      dysfunction.
AB  - Implanted cardioverter defibrillator therapy has been shown to be associated with
      a significant reduction in the risk of sudden cardiac death (SCD) in patients
      with ischemic left ventricular dysfunction. However, data on the relation between
      renal function and SCD in this population are limited, and the effect of renal
      dysfunction on the implanted cardioverter defibrillator benefit has not been
      determined. We performed a retrospective analysis of the outcome associated with
      renal dysfunction, as determined by the estimated glomerular filtration rate
      (eGFR), in patients enrolled in the Multicenter Automatic Defibrillator
      Implantation Trial-II. Multivariate analysis in conventionally treated patients
      showed that for each 10-U reduction in eGFR, the risk of all-cause mortality and
      SCD increased by 16% (p = 0.005) and 17% (p = 0.03), respectively. Defibrillator
      therapy was associated with a survival benefit in each eGFR category of > or = 35
      ml/min/1.73 m2 (overall risk reduction for all-cause mortality 32%, p = 0.01 and
      for SCD 66%, p < 0.001). However, no implanted cardioverter defibrillator benefit
      was shown among patients with an eGFR < 35 ml/min/1.73 m2 (all-cause mortality
      hazard ratio 1.09, p = 0.84; SCD hazard ratio 0.95, p = 0.95). In conclusion, in
      patients with high-risk cardiac disease enrolled in the Multicenter Automatic
      Defibrillator Implantation Trial-II, a significant increase was found in the risk
      of SCD with declining renal function. Defibrillator therapy was associated with a
      significant survival benefit among the study patients with mild to moderate or no
      renal disease, but no benefit was shown among patients with more advanced renal
      dysfunction.

PMID- 16893704
TI  - Three-phase model of cardiac arrest: time-dependent benefit of bystander
      cardiopulmonary resuscitation.
AB  - Evidence has suggested that the pathophysiology of ventricular fibrillation
      cardiac arrest may consist of 3 time-sensitive phases: electrical, circulatory,
      and metabolic. We performed a retrospective cohort study of adults in a
      metropolitan county who had had witnessed ventricular fibrillation arrest before
      emergency medical services were undertaken to investigate this 3-phase model with
      regard to bystander cardiopulmonary resuscitation (CPR). We hypothesized that the
      survival benefit from bystander CPR depends on the collapse-to-shock interval,
      with the highest benefit occurring during the circulatory phase. The collapse-to
      shock interval was a priori grouped into 4 categories: 1 to 5, 6 to 7, 8 to 10,
      and > or = 11 minutes. We used logistic regression analysis to assess whether the
      association between CPR and survival to hospital discharge depended on the
      collapse-to-shock interval category. Of the 2,193 events meeting the inclusion
      criteria, 67.0% had received bystander CPR. The average collapse-to-shock
      interval was 8.2 +/- 2.8 minutes. The survival rate was 33.4%. A higher
      likelihood of survival was associated with bystander CPR (odds ratio [OR] 1.41,
      95% confidence interval [CI] 1.15 to 1.73) and a shorter collapse-to-shock
      interval (OR -1.84, 95% CI 1.62 to 2.10, for each additional SD of 2.8 minutes
      less) after adjustment. The beneficial association of CPR increased as the
      collapse-to-shock interval increased (p = 0.05 for interaction). The bystander
      CPR was associated with an OR of survival of 0.96 (95% CI 0.64 to 1.46) for a 1-
      to 5-minute collapse-to shock interval, OR of 1.25 (95% CI 1.00 to 1.58) for a 6-
      to 7-minute interval, OR of 1.62 (95% CI 1.25 to 2.11) for an 8- to 10-minute
      interval, and OR of 2.11 (95% CI 1.32 to 3.37) for an > or = 11-minute interval.
      The results of this investigation support a phased model of ventricular
      fibrillation arrest. The findings suggest that the transition from the electrical
      to circulatory phase may occur at about 5 minutes, and the circulatory phase may
      extend to 15 minutes.

PMID- 16893705
TI  - Prognostic value of cardiopulmonary exercise variables in chronic heart failure
      patients with or without beta-blocker therapy.
AB  - The prognostic value of exercise-derived variables in the prediction of mortality
      in patients with chronic heart failure treated by beta blockers continues to be
      debated. A total of 402 patients with chronic heart failure, including 255
      treated with beta blockers, were included and followed for 26 +/- 20 months after
      the exercise test. On univariate analysis, and in contrast to peak exercise
      oxygen consumption, the prognostic value of the minute ventilation/carbon dioxide
      production slope was increased in patients receiving beta-blocker therapy. On
      multivariate analysis, no independent prognostic variable emerged in patients not
      on beta-blocker therapy. However, the model that included the circulatory power
      (peak oxygen uptake x systolic blood pressure), in addition to age, New York
      Heart Association class, and left ventricular ejection fraction, was the best 1
      for patients on beta-blocker therapy. In conclusion, in patients with chronic
      heart failure, the circulatory power is the exercise variable with the greatest
      independent prognostic value, compared with the peak exercise oxygen consumption
      and minute ventilation/carbon dioxide production slope.

PMID- 16893706
TI  - Echocardiographic predictors of successful versus unsuccessful mitral valve
      repair in ischemic mitral regurgitation.
AB  - Mitral valve (MV) annuloplasty is the standard surgical technique for the
      management of ischemic mitral regurgitation (MR). However, < or = 1/3 of patients
      develop recurrent MR after annuloplasty. Therefore, we sought to identify the
      preoperative echocardiographic parameters that predict annuloplasty failure in
      patients with ischemic MR. Intraoperative transesophageal echocardiograms from
      365 patients who underwent MV repair for ischemic MR were reviewed. Of the 365
      patients, 297 (81%) had satisfactory outcomes with < 2+ MR, and 68 (19%) had
      recurrent MR (> or = 2+) during a mean follow-up of 269 days. The mitral annular
      parameters, including mitral annular diameter, tethering height, and tethering
      area of the mitral leaflets, were determined in 3 different echocardiographic
      views. On multiple logistic stepwise regression analysis, a higher mitral annular
      diameter, higher tethering area, and higher MR severity were identified as
      independent predictors for failure of MV repair (p < 0.0001). In conclusion,
      these results demonstrated that preoperative echocardiographic findings can be
      used to identify patients with ischemic MR at increased risk of repair failure.
      These echocardiographic measurements should be used to guide the cardiologist and
      cardiac surgeon in the choice of MV repair versus replacement in patients with
      ischemic MR.

PMID- 16893707
TI  - "Isolated" diastolic dysfunction in left ventricular outflow tract obstruction.
AB  - We sought to investigate the prescence of "isolated" diastolic disease, defined
      as reduced long-axis early diastolic velocity with normal systolic velocity, in
      21 young patients with left outflow tract obstruction. Most patients had
      depressed systolic velocities despite normal ejection fractions. The close
      relations amond long-axis velocities suggest isolated diastolic disease is
      unlikely.

PMID- 16893708
TI  - Usefulness of N-terminal pro-B-type natriuretic peptide levels to predict
      exercise capacity in hypertrophic cardiomyopathy.
AB  - Most patients with hypertrophic cardiomyopathy (HC) have reduced maximal oxygen
      consumption (VO2max) during exercise. The degree of impairment is poorly
      predicted by the magnitude of hypertrophy, left ventricular (LV) outflow tract
      obstruction, and other conventional markers of disease severity. The aim of this
      study was to determine the usefulness of N-terminal-pro-B-type natriuretic
      peptide (NT-pro-BNP) as a marker of exercise performance in HC. Plasma NT-pro-BNP
      was measured in 171 consecutive patients (mean age 46 +/- 18 years) who underwent
      echocardiography and cardiopulmonary exercise testing. The mean log NT-pro-BNP
      was 2.79 +/- 0.5; log NT-pro-BNP levels were higher in women patients (p = 0.001)
      and patients with chest pain (p = 0.010), in New York Heart Association class >
      or = II (p = 0.009), with atrial fibrillation (p < 0.001), with systolic
      impairment (p = 0.025), and with LV outflow tract obstructions (p < 0.0001). NT
      pro-BNP levels were also correlated with maximal wall thickness (r = 0.335, p <
      0.0001), left atrial size (r = 0.206, p = 0.007), and the mitral Doppler E/A
      ratio (r = 0.197, p = 0.012). The mean percent VO2max achieved was 73.8 +/-
      22.6%; percent VO2max was smaller in patients with systolic impairment (p =
      0.044) and LV outflow tract obstructions (p = 0.025). There were inverse
      correlations between percent VO2max and NT-pro-BNP (r = -0.352, p = 0.001), LV
      end-systolic cavity size (r = -0.182, p = 0.031), and left atrial size (r = 
      0.251, p = 0.003). On multivariate analysis, only NT-pro-BNP was correlated with
      percent VO2max. A NT-pro-BNP level of 316 ng/L had 78% sensitivity and 44%
      specificity (area under the curve 0.616) for predicting percent VO2max < 80%. In
      conclusion, NT-pro-BNP levels correlate with peak oxygen consumption in HC and
      are more predictive of functional impairment than other conventional markers of
      disease severity.

PMID- 16893709
TI  - Comparison of plasma B-type natriuretic peptide levels in single ventricle
      patients with systemic ventricle heart failure versus isolated cavopulmonary
      failure.
AB  - The measurement of plasma B-type natriuretic peptide (BNP) has emerged as a
      useful biomarker of heart failure in patients with cardiomyopathy. The
      pathophysiology of heart failure in single ventricle (SV) circulation may be
      distinct from that of cardiomyopathies. A distinct pattern of BNP elevation in
      heart failure in the SV population was hypothesized: it is elevated in heart
      failure secondary to ventricular dysfunction but not in isolated cavopulmonary
      failure. BNP was measured prospectively in SV patients at catheterization (n =
      22) and when assessing for heart failure (n = 11) (7 normal controls). Of 33 SV
      subjects (median age 62 months), 13 had aortopulmonary connections and 20 had
      cavopulmonary connections. Median and mean +/- SD BNP levels by shunt type were
      184 and 754 +/- 1,086 pg/ml in the patients with aortopulmonary connections, 38
      and 169 +/- 251 pg/ml in the patients with cavopulmonary connections, and 10 and
      11 +/- 5 pg/ml in normal controls, respectively (p = 0.004). Median systemic
      ventricular end-diastolic pressure (8mm Hg, R = 0.45), mean pulmonary artery
      pressure (14.5 mm Hg, R = 0.62), and mean right atrial pressure (6.5 mm Hg, R =
      0.54) were correlated with plasma BNP. SV subjects with symptomatic heart failure
      from dysfunctional systemic ventricles had median and mean +/- SD BNP levels of
      378 and 714 +/- 912 pg/ml (n = 18) compared with patients with isolated failed
      Glenn or Fontan connections (19 and 23 +/- 16 pg/ml [n = 7, p = 0.001]) and those
      with no heart failure (22 and 22 +/- 12 pg/ml [n = 8, p = 0.001]). Excluding the
      group with cavopulmonary failure, the severity of heart failure from systemic
      ventricular dysfunction was associated with plasma BNP. In conclusion, plasma BNP
      is elevated in SV patients with systemic ventricular or left-sided cardiac
      failure. BNP is not elevated in patients missing a pulmonary ventricle with
      isolated cavopulmonary failure.

PMID- 16893711
TI  - Right ventricular function assessed by two-dimensional strain and tissue Doppler
      echocardiography in patients with pulmonary arterial hypertension and effect of
      vasodilator therapy.
AB  - Two-dimensional strain echocardiography is a new method for the assessment of
      regional contractility. Thirty-seven patients with pulmonary arterial
      hypertension (mean age 56.4 +/- 11 years) and 38 normal subjects (mean age 58.3
      +/- 12 years) underwent 2-dimensional echocardiography and tissue Doppler
      echocardiographic evaluation of right ventricular (RV) global function and
      regional contractility. Patients with pulmonary arterial hypertension
      additionally underwent 6-minute walking distance tests and right-sided cardiac
      catheterization before and after (8 +/- 3 months) vasodilator therapy. Moderate
      or severe RV dysfunction was present in all patients (2-dimensional strain of the
      basal segment of the RV free wall: -8.8 +/- 4.1% systolic longitudinal
      deformation) compared with normal subjects (-24.3 +/- 4.7% systolic longitudinal
      deformation, p < 0.001) and was improved with vasodilator therapy after 6 to 11
      months (-13.3 +/- 6.2% systolic longitudinal deformation, p < 0.001).

PMID- 16893710
TI  - N-terminal pro-B-type natriuretic peptide as an indicator of disease severity in
      a heterogeneous group of patients with chronic precapillary pulmonary
      hypertension.
AB  - N-terminal-pro-B-type natriuretic peptide (NT-pro-BNP) is well established as a
      predictor of prognosis in patients with left ventricular dysfunction. Although a
      similar prognostic significance has been suggested in 1 study of right
      ventricular failure and idiopathic pulmonary arterial hypertension, NT-pro-BNP
      has not been assessed as a marker of disease severity in a more heterogenous
      group of patients with chronic precapillary pulmonary hypertension (PH). Hence,
      this study assessed plasma NT-pro-BNP and other clinical variables in 61
      consecutively recruited patients with various forms of chronic precapillary PH.
      Right-sided cardiac catheterization and cardiopulmonary exercise testing were
      performed at baseline, and the prognostic significance of NT-pro-BNP was
      investigated with a mean follow-up of 25 months. Compared with age-matched
      controls (n = 10), plasma NT-pro-BNP was significantly greater in those with
      idiopathic pulmonary arterial hypertension (n = 16), chronic precapillary PH
      associated with other diseases (n = 26), and chronic thromboembolic disease (n =
      19) and was correlated with hemodynamic variables and functional capacity. In 17
      medically treated patients, the significant decrease in NT-pro-BNP levels
      correlated with improved hemodynamics. During follow-up, 15 patients died from
      cardiopulmonary causes. Baseline NT-pro-BNP was an independent predictor of
      mortality. Kaplan-Meier survival analysis according to the median value of NT-pro
      BNP (168 pmol/L) demonstrated a significantly higher mortality rate in those with
      supramedian values than in those with low plasma levels (p = 0.010). In
      conclusion, these findings suggest that in a heterogenous group of patients with
      chronic precapillary PH, plasma NT-pro-BNP can be used to determine the clinical
      severity of disease and is independently associated with long-term mortality.

PMID- 16893712
TI  - Comparison of a single end point to determine optimal initial warfarin dosing (5
      mg versus 10 mg) for venous thromboembolism.
AB  - There remains considerable controversy regarding optimal initial warfarin dosing
      in patients with acute venous thromboembolism. Therefore, an open-label,
      randomized trial comparing 2 warfarin initiation nomograms (5 vs 10 mg) was
      conducted in patients with acute venous thromboembolism. All participants
      received fondaparinux for > or = 5 days as a "bridge" to warfarin. The primary
      end point was defined as the number of days necessary to achieve 2 consecutive
      international normalized ratio laboratory test values > 1.9. A total of 50
      patients were enrolled and randomly assigned to each of the treatment arms. The
      median time to 2 consecutive international normalized ratios was 5 days in the 2
      groups. There was no statistical difference in achieving the primary end point
      using either the 5- or the 10-mg nomogram (p = 0.69). These results should
      provide clinicians with increased warfarin dosing options in patients presenting
      with acute venous thromboembolism.

PMID- 16893714
TI  - Safety of stress echocardiography (from the International Stress Echo
      Complication Registry).
AB  - The safety of any diagnostic test is a major issue in deciding its practicability
      and cost-effectiveness. The aim of this study was to evaluate the safety of
      various stress echocardiographic modalities in the "real world." From February
      1998 to January 2004, a simple written questionnaire was distributed to
      echocardiography laboratories across the world known to perform stress
      echocardiography. The following categories of major complications (known to occur
      during stress testing) were indicated: sustained ventricular tachycardia (> 30
      beats/min), ventricular fibrillation, myocardial infarction, third-degree
      atrioventricular block, severe hypotension requiring therapy, cardiac asystole,
      cardiac rupture, stroke, and death. Three hundred centers were polled, from which
      71 co-investigators responded and reported on 85,997 patient examinations.
      Exercise was used in 26,295 cases, dobutamine in 35,103, and dipyridamole in
      24,599 cases. Life-threatening events occurred in 86 cases: during exercise in 4
      patients (event rate 1 in 6,574), during dobutamine infusion (small dose for
      viability and/or large dose for ischemia) in 63 patients (event rate 1 in 557),
      and during dipyridamole stress testing in 19 patients (event rate 1 in 1,294). Of
      the 86 patients with complications, 5 died during dobutamine stress testing
      (ventricular fibrillation, n = 2; cardiac rupture, n = 3) and 1 after
      dipyridamole testing (cardiogenic shock). In conclusion, stress echocardiography
      is a safe method in the real world, but serious complications may occur. Exercise
      seems safer than pharmacologic stress and dipyridamole safer than dobutamine,
      possibly because of preselection criteria.

PMID- 16893715
TI  - Enhanced 11beta-hydroxysteroid dehydrogenase activity, the metabolic syndrome,
      and systemic hypertension.
AB  - Metabolic syndrome, with its attendant cardiovascular complications, is reaching
      epidemic proportions worldwide; hence, there is intense interest in understanding
      the pathogenesis of and developing therapy for these common disorders. Recent
      studies have suggested that metabolic syndrome may be a stress response, with an
      underlying abnormality in the enzyme 11beta-hydroxysteroid dehydrogenase. At the
      cellular level, the enzyme hydroxysteroid dehydrogenase type 1 (HSD1) locally
      regenerates active cortisol from inactive cortisone, amplifying glucocorticoid
      receptor activation and promoting preadipocyte differentiation and adipocyte
      hypertrophy. Although initial studies in transgenic mice and humans are
      encouraging, more data are required to conclusively prove the hypothesis that the
      adipose-tissue-specific overexpression of HSD1 and the resultant increase in
      tissue-specific cortisol concentrations result in human obesity, insulin
      resistance, high blood pressure, and metabolic syndrome. Currently, selective
      inhibitors of HSD1 are not available for human use; however, their development is
      under way. The use of potent and selective HSD1 inhibitors will finally confirm
      or refute this hypothesis and may turn out to be an effective strategy for
      combating these common maladies.

PMID- 16893713
TI  - Relation of brain natriuretic peptide levels to cognitive dysfunction in adults >
      55 years of age with cardiovascular disease.
AB  - Cardiovascular disease (CVD) is associated with cognitive deficits long before
      the onset of stroke or dementia. Recent work has extended these findings and
      shown that patients with congestive heart failure also exhibit reduced cognitive
      performance. Brain natriuretic peptide (BNP) is used to help diagnose heart
      failure, but no study has examined whether BNP predicts cognitive dysfunction in
      older patients with CVD. BNP values and performance on the Dementia Rating Scale
      were assessed in 56 older adults with documented CVD. Forty-eight percent of the
      participants were women, and their average age was 70 +/- 8 years. All
      participants had Mini-Mental State Examination scores greater than the cutoff for
      dementia and no histories of neurologic or severe psychiatric disorders. The
      average BNP level was 122 +/- 202 pg/ml. Hierarchical regression analyses showed
      that log-transformed BNP levels predicted Dementia Rating Scale total score after
      adjusting for possible demographic and medical confounders (DeltaR2 = 0.09, F[1,
      44] = 6.14, p = 0.017). Partial correlation analysis adjusting for these possible
      confounders showed a particularly strong relation to the conceptualization
      subtest (r = -0.44, p = 0.002), a measure of verbal and nonverbal abstraction
      abilities. In conclusion, the results of the present study provide the first
      evidence for an independent relation between BNP and cognitive dysfunction in
      older adults with CVD.

PMID- 16893716
TI  - Systematic overview and clinical applications of pacing atrial stress
      echocardiography.
AB  - Pacing atrial stress echocardiography (PASE) has been studied over the past 3
      decades for the evaluation of myocardial ischemia. Published studies suggest that
      PASE may be used as an alternative to exercise or pharmacologic stress imaging.
      The recent introduction of improved pacing electrodes, together with use of
      accelerated and shortened pacing protocols and improvements in transthoracic
      echocardiographic imaging techniques, makes PASE an appealing stress imaging
      method. A critical analysis of the diagnostic accuracy of PASE shows equivalence
      with other imaging stress modalities. PASE has been found to be highly feasible
      and accurate technique that may expedite the diagnosis and risk stratification of
      patients with coronary artery disease. This review addresses the history,
      hemodynamics, protocols, accuracy, clinical utility, and cost-effectiveness of
      PASE as well as elucidating its place among other stress modalities.

PMID- 16893717
TI  - Effects of outcome on in-hospital transition from intravenous insulin infusion to
      subcutaneous therapy.
AB  - It is widely accepted by medical practitioners that diabetes is a major
      independent risk factor for the development of cardiovascular disease. However,
      less attention has been directed toward elevated blood glucose as a predictor of
      poor outcomes in hospitalized patients in cardiac critical care. This has
      occurred despite documentation of hyperglycemia in a significant proportion of
      patients admitted for cardiac care and considerable data supporting the use of
      intravenous (IV) insulin to achieve glycemic control. The increased risk for
      mortality due to hyperglycemia provides a strong rationale for an intensive
      approach using insulin to control blood glucose levels in cardiac patients being
      treated in acute care and surgical settings. IV insulin infusion is the therapy
      of choice for patients in cardiac critical care units, with transition to a
      subcutaneous insulin therapy regimen when appropriate. The timing of this
      transition can be critical. Strong evidence from studies on patients who have
      undergone cardiac surgery suggests that glycemic control by insulin infusion
      should be maintained for > or =3 postoperative days. Nonetheless, transition from
      IV to subcutaneous therapy must occur at some point during the hospital stay. In
      conclusion, the implementation of measures to achieve glycemic control in acute
      cardiac care hospital settings can significantly reduce morbidity and mortality
      and can substantially decrease the costs associated with prolonged hospital
      stays. This report reviews recent clinical data on the benefits of IV insulin
      infusion in cardiac patients in critical care and provides recommendations on
      transitioning patients from IV insulin infusion to subcutaneous therapy.

PMID- 16893718
TI  - Psychological aspects of cardiac devices and recalls in patients with implantable
      cardioverter defibrillators.
AB  - The product recall of an implantable cardioverter defibrillator (ICD) creates a
      potentially stressful event for patients. This study briefly describes the
      psychological adjustment of patients with implantable devices and makes
      recommendations for the management of device recalls and adverse outcomes to
      minimize psychological distress. Because the occurrence of ICD-specific fears and
      symptoms of anxiety are the most common psychological symptoms experienced by ICD
      recipients, a comprehensive care plan to attend to recall procedures and patient
      distress is needed. It is suggested that recalls do not affect all ICD patients
      equally, with risk factors for poor psychological adjustment to ICDs including
      younger age (< 50 years), shock experience, and female gender that may be
      associated with increased recall anxiety. Specific recommendations for device
      recall management include formalizing clinic responses to recall before and after
      implantation and innovative uses of patient support systems to communicate recall
      responses.

PMID- 16893719
TI  - Beta blockers versus diuretics for congestive heart failure in African-American
      patients.

PMID- 16893720
TI  - Evaluation of isolated left ventricular noncompaction is suboptimal by two
      dimensional transthoracic echocardiography alone.

PMID- 16893721
TI  - Echocardiographic quantitative estimation of left ventricular ejection fraction
      from mitral septal angle.

PMID- 16893722
TI  - Effects of thrombolysis in out-of-hospital cardiac arrest.

PMID- 16893723
TI  - Cellular senescence and DNA repair.
AB  - Aging is a complex process that results in functional decline and mortality of
      the organisms. On the cellular lever, cellular senescence has been used as a
      model for aging. Therefore, understanding cellular senescence has important
      health implications. Initial observations suggest that cellular senescence is the
      result of telomere shortening. Recent findings suggest that cellular senescence
      could be triggered by DNA damage. In fact, both telomere shortening and DNA
      damage-induced cellular senescence share a common mechanism, the DNA damage
      response pathway. This review will discuss the link between DNA repair defects
      and cellular senescence.

PMID- 16893724
TI  - Chromatin modulation and the DNA damage response.
AB  - The ability to sense and respond appropriately to genetic lesions is vitally
      important to maintain the integrity of the genome. Emerging evidence indicates
      that various modulations to chromatin structure are centrally important to many
      aspects of the DNA damage response (DDR). Here, we discuss recently described
      roles for specific post-translational covalent modifications to histone proteins,
      as well as ATP-dependent chromatin remodelling, in DNA damage signalling and
      repair of DNA double strand breaks.

PMID- 16893727
TI  - Consensus forum: worldwide guidelines on the critical care nursing workforce and
      education standards.
AB  - This article explores the key themes, evidence, and arguments that inform the
      current position statements. It is acknowledged that future research, evidence,
      and practice experience may create the need to review and change these
      guidelines. Reform and refinement of the guidelines are inevitable; however, the
      current guidelines represent the best attempt yet to reach international
      consensus on what are appropriate standards to guide critical care nursing
      education and workforce requirements.

PMID- 16893726
TI  - The World Federation: enhancing global critical care practice and performance.
AB  - The World Federation of Societies of Intensive and Critical Care Medicine is an
      international organization composed of 42 members of national societies of
      intensive and critical care medicine representing approximately 38,000 physicians
      and allied health professionals. To appreciate the importance of international
      collaboration in various specialties, it is imperative to recognize not only the
      similarities within health systems, but also to recognize the international focus
      of disease.

PMID- 16893728
TI  - Intensive care in Australia and New Zealand.
AB  - This article provides an up-to-date account of intensive care in Australia and
      New Zealand. Overall, intensive care medicine in Australia and New Zealand is in
      a healthy state. It began early and has developed into a distinct and strong
      medical specialty. There are well-developed organizations dealing with all
      aspects of the specialty. The ICU is recognized as an expensive and limited
      resource. Overall, intensivists in these two countries have good control of it
      and have learned to use it wisely.

PMID- 16893729
TI  - Intensive care medicine in Europe.
AB  - Health care systems stem from specific political, historical, cultural,and
      socioeconomic traditions. As a result, the organizational arrangements for health
      care differ considerably between Member States of the European Union. Health care
      in the European Union is at a crossroads between challenges and opportunities.
      The Member States are facing common challenges in delivering equal, efficient,
      and high-quality health services at affordable cost in times when the amount of
      care to be delivered is starting to exceed the resource base.

PMID- 16893730
TI  - Critical care in Africa.
AB  - This article identifies the key challenges facing critical care practitioners in
      Africa. As a continent with a large proportion of the poorest countries and a
      plethora of unique diseases that place large demands for critical resources, the
      provision of care is largely in the context of severely constrained human and
      material resources. Diverse cultures and social norms predicate sensitivity to
      community values in the provision of care. Such realities demand novel approaches
      to the provision of critical care.

PMID- 16893731
TI  - Critical care in Latin America: current situation.
AB  - Critical care has grown significantly in Latin America. This grow this caused by
      the increase in the number of patients requiring this specialized care for whom
      excellent outcomes are achieved with the indisputable development of critical
      care. There is an increasing interest for the application of systems ensuring
      quality medical care, a reason why some countries have decided to make critical
      care part of their legislation. Because of the economic conditions in the region
      there is a marked difference in the number of intensive care beds among Latin
      American countries compared with European countries and the United States.
      Standards are being prepared to establish minimum human and physical resource
      requirements to ensure that existing beds are equipped as best as possible.

PMID- 16893733
TI  - Controversial aspects of the prehospital trauma care.
AB  - Despite decades of studies and experiences, an evidence-based medicine consensus
      on the more appropriate treatment of trauma patients in the out-of-hospital
      setting has not yet been achieved. Different approaches exist and no one has been
      demonstrated clearly superior over the others for all circumstances and for all
      patients. A number of factors likely account for this finding.

PMID- 16893732
TI  - Critical care in the United States of America.
AB  - There are numerous factors that continue to influence the practice of critical
      care medicine. This article focuses on issues that have significantly impacted
      critical care practice during the last decade, such as changing socioeconomic
      factors, the increasing influence of specialty groups and governmental agencies,
      and the translation of evidence-based medicine into practice.

PMID- 16893735
TI  - Management of severe sepsis and septic shock: challenges and recommendations.
AB  - Sepsis and related aspects has become an area of active and intense research,
      leading to important advances for an early diagnosis and appropriate management
      useful to improve patient outcome. The septic response is an extremely complex
      cascade of events, including proinflammatory, anti-inflammatory, humoral,
      cellular, and circulatory involvement. The pathophysiology of this syndrome, its
      various and changing clinical aspects, and the vast variety of therapeutic
      options available, not always of well-proved efficacy, make its management a goal
      difficult to achieve.

PMID- 16893734
TI  - Global distribution of infectious diseases requiring intensive care.
AB  - This article describes infectious diseases that are of special importance to
      intensivists. The emphasis on epidemiology notwithstanding, it also addresses
      clinical, diagnostic, and treatment issues related to each infection described.
      The discussion avoids terrorism-related aspects of these infections, because they
      were very well covered in the October 2005 issue of the Critical Care Clinics.

PMID- 16893738
TI  - New cardiopulmonary resuscitation guidelines 2005: importance of uninterrupted
      chest compression.
AB  - The evidence supports quality controlled chest compression as the initial
      intervention after "sudden death" before attempted defibrillation, if the
      duration of cardiac arrest is more than 5 minutes. The new guidelines mandate
      lesser interruptions for ventilation, before and following electrical shocks, and
      single rather than multiple electrical shocks before resuming chest compression.
      The new guidelines refocus on uninterrupted chest compression after cardiac
      arrest of nonasphyxial cause and modifications in practices that reduce the need
      for interruptions.

PMID- 16893737
TI  - The role of bundles in sepsis care.
AB  - The understanding of the pathogenesis of sepsis has substantially changed in past
      years and continues to improve. New therapeutic options are being developed and
      incorporated into clinical practice. There are different specific interventions
      and therapies that benefit patients' outcome. As demonstrated by the early goal
      directed therapy strategy, the success of the resuscitation treatment is strongly
      time dependent. The recognition of severe sepsis should be accompanied without
      delay by very well defined therapeutic measures. In 2002 the Surviving Sepsis
      Campaign was introduced with the overall goal of increasing clinicians' awareness
      and improving outcome in severe sepsis and septic shock.

PMID- 16893736
TI  - Markers for sepsis diagnosis: what is useful?
AB  - Timely diagnosis of the different severities of septic inflammation is
      potentially lifesaving because therapies that have been shown to lower mortality
      should be initiated early. Sepsis and severe sepsis are accompanied by clinical
      and laboratory signs of systemic inflammation but patients with inflammation
      caused by noninfectious causes may present with similar signs and symptoms. It is
      important to identify markers for an early diagnosis of sepsis and organ
      dysfunction. This article presents currently interesting sepsis biomarkers. Other
      novel markers and their potential role are discussed.

PMID- 16893739
TI  - A global view of education and training in critical care medicine.
AB  - The Educational Committee of the World Federation of Societies of Intensive and
      Critical Care Medicine (WFSICCM) performed a survey in various countries and
      reviewed data from the Cobatrice study and from surveys of the Pan-American and
      Iberic Federation of Societies of Intensive and Critical Care Medicine to
      characterize current structures and processes in education in intensive care
      medicine to determine the potential for convergence to a common competency-based
      training program, and to a common competency certification in most countries
      around the world, guided by the local scientific societies and the WFSICCM.
      Training in critical care medicine sponsored by the WFSICCM should provide a
      competency approach that permits diversity of training methods while creating a
      common outcome: doctors with a universal set of knowledge, skills, and attitudes
      essential for a specialist in intensive care medicine.

PMID- 16893740
TI  - Improving quality in the intensive care unit setting.
AB  - Summarizing the mission of the ICU, the institution directive board and the unit
      director must generate a structure, proceedings criteria, management, and
      analysis of results capable of providing satisfactory care. Furthermore, they
      must take into account each organizational aspect that is necessary to offer an
      appropriate service for the patient. Medicine in general and intensive care in
      particular require that precautions be taken to avoid the patient and family
      feeling uncertain and fearful about the quality of the attention and care they
      receive.

PMID- 16893742
TI  - Skin and wound assessment and care in oncology.
AB  - OBJECTIVES: To present an in-depth overview of skin and wound assessment and care
      that will provide a solid foundation to better understand the effects of
      treatment and cancer on skin and wound care in oncology patients. DATA SOURCES:
      Current research and published literature. CONCLUSION: Adequate skin and wound
      assessment and care are essential to maintaining adequate quality of life and
      decreasing morbidity and mortality in oncology patients. IMPLICATIONS FOR NURSING
      PRACTICE: Any systematic changes in skin and wound care practices for patients
      with cancer will be led by oncology nurses. Thus, a broad understanding of skin
      and wounds is essential.

PMID- 16893743
TI  - Chemotherapy and cutaneous toxicities: implications for oncology nurses.
AB  - OBJECTIVE: To review common cutaneous effects and dermatologic or cutaneous
      toxicities related to the administration of chemotherapy. These range from mostly
      cosmetic, such as hyperpigmentation or alopecia, to dose-limiting toxicities such
      as palmar-plantar erythrodysesthesia or hand-foot syndrome. DATA SOURCES: Current
      research, published literature, and internet resources. CONCLUSION: Assessment
      and grading of associated toxicities of therapy is an integral part of caring for
      this patient population. Early intervention may reduce toxicities associated with
      therapies for this patient population IMPLICATIONS FOR NURSING PRACTICE: As more
      patients receive chemotherapy, dermatologic effects are becoming more common.
      Oncology nurses must be skilled in managing these side effects.

PMID- 16893744
TI  - EGFR-targeted therapy and related skin toxicity.
AB  - OBJECTIVES: To discuss the mechanism by which epidermal growth factor receptor
      (EGFR)-targeted agents work, the resulting cutaneous toxicities, the
      pathophysiology of the unique rash associated with these agents, and the
      management of these skin problems. DATA SOURCES: Published scientific papers,
      review articles, book chapters, and clinical experiences. CONCLUSION: These new
      targeted agents result in unique cutaneous toxicities. Researchers and clinicians
      have made numerous suggestions for managing the various side effects, although
      there is currently no research to guide evidence-based practice. IMPLICATIONS FOR
      NURSING PRACTICE: With any new treatment option, it is imperative that nurses
      understand how agents work to enrich their own knowledge base, as well as have a
      strong foundation for patient education. It is important that nurses understand
      potential side effects of these agents, know of possible interventions, and
      participate in research to identify effective interventions.

PMID- 16893745
TI  - Evidence-based skin care management in radiation therapy.
AB  - OBJECTIVES: To review published studies evaluating interventions for the
      prevention and management of radiation skin reactions/dermatitis. DATA SOURCES:
      Research studies, review articles, and clinical practice guidelines. CONCLUSION:
      There is insufficient evidence in the literature to recommend specific topical or
      oral agents in the prevention or management of skin reactions. Recent limited
      evidence suggests that the use of calendula cream may reduce the incidence of
      grade 2 and 3 reactions in women with breast cancer. Additionally, early studies
      evaluating the use of barrier films or creams may improve moist desquamation.
      IMPLICATIONS FOR NURSING PRACTICE: Oncology nurses need to increase their
      awareness of the evidence or lack of evidence when recommending interventions to
      their patients. Further research is required to evaluate interventions in the
      prevention and management of radiation dermatitis.

PMID- 16893746
TI  - Ostomy care and rehabilitation in colorectal cancer.
AB  - OBJECTIVES: To review ostomy care in colorectal cancer, current trends in
      assessment, management, and treatment, and the role of the enterostomal therapy
      (ET) nurse in cancer care. DATA SOURCES: Published literature and the author's
      clinical experiences in ostomy wound care. CONCLUSION: Care of the patient with
      colorectal cancer requiring an ostomy involves both physical and psychological
      rehabilitation. The education and skills of an ET/wound, ostomy, and continence
      (WOC) nurse can provide a valuable service to the patient/family, surgeon,
      oncology nurse, and other health care providers. IMPLICATIONS FOR ONCOLOGY
      NURSES: An ostomy is not a handicapping procedure. Living well with a colostomy
      can be achieved through proper patient preparation, education, and planning.
      Provision of individualized comprehensive care facilitates physical and
      psychological rehabilitation.

PMID- 16893747
TI  - Assessing risk and preventing pressure ulcers in patients with cancer.
AB  - OBJECTIVE: To identify risk factors for pressure ulcers that may place the
      patient with cancer at higher risk. The role of nursing to provide pressure ulcer
      preventive measures will be discussed. DATA SOURCES: Current research and
      published literature CONCLUSION: Research suggests that comprehensive prevention
      programs are effective in reducing pressure ulcer incidence rates and can be cost
      effective. Comprehensive pressure ulcer prevention guidelines include risk
      assessment, skin care, offloading, and nutrition. Immobility places patients with
      cancer at greater risk. IMPLICATIONS FOR NURSING PRACTICE: Nurses are at the
      forefront of predicting patients at risk for pressure ulcers and working with the
      multidisciplinary team to implement a pressure ulcer preventive program. There
      remains a dearth of research related to pressure ulcers and cancer. Research in
      this area is strongly suggested.

PMID- 16893748
TI  - Management of malignant fungating wounds in advanced cancer.
AB  - OBJECTIVE: To review the pathophysiology and assessment of malignant wounds and
      management techniques aimed at controlling pain, odor, exudate, and local
      bleeding. DATA SOURCES: Current research and published literature. CONCLUSION:
      Assessment of malignant wounds, selection of appropriate dressings, related
      symptom management, and patient and family support are vital aspects of cutaneous
      wound management in advanced cancer. IMPLICATIONS FOR NURSING PRACTICE: A
      thorough understanding of the care of malignant wounds will assist oncology
      nurses achieving palliative goals of care including optimal symptom management,
      odor and drainage control, and emotional support.

PMID- 16893749
TI  - Bioconversions of ferulic acid, an hydroxycinnamic acid.
AB  - Ferulic acid is the most abundant hydroxycinnamic acid in the plant world and is
      ester linked to arabinose, in various plant polysaccharides such as arabinoxylans
      and pectins. It is a precursor to vanillin, one of the most important aromatic
      flavor compound used in foods, beverages, pharmaceuticals, and perfumes. This
      article presents an overview of the various biocatalytic routes, focusing on the
      relevant biotransformations of ferulic acid using plant sources, microorganisms,
      and enzymes.

PMID- 16893750
TI  - Cyanobacteria metal interactions: requirements, toxicity, and ecological
      implications.
AB  - The environmental health-related relevance of cyanobacteria is primarily related
      to their ability to produce a wide range of toxins, which are known to be
      hazardous to many organisms, including human beings. The occurrence of
      cyanobacterial blooms has been related to eutrophic surface water. In the bloom
      forming process the levels of phosphorus and nitrogen have been well documented
      but information regarding concentrations of other chemicals (inorganic, organo
      metallic, and organic) is still incipient. Several contaminants, like trace
      metals, elicit a variety of acute and chronic toxicity effects, but cyanobacteria
      also have the capability to accumulate, detoxify, or metabolize such substances,
      to some extent. The role of cyanobacterial exudates has been proved a means of
      both nutrient acquisition and detoxification. In addition, cyanobacteria are
      effective biological metal sorbents, representing an important sink for metals in
      aquatic environment. Understanding the fundamental physicochemical mechanisms of
      trace metal bio-uptake by cyanobacteria in natural systems is a step towards
      identifying under what conditions cyanobacterial growth is favored and to
      ascertain the mechanisms by which blooms (and toxin production) are triggered. In
      this review the cyanobacterial interactions with metals will be discussed,
      focusing on freshwater systems.

PMID- 16893751
TI  - Streptococcus pneumoniae protein vaccine candidates: properties, activities and
      animal studies.
AB  - Streptococcus pneumoniae is a causative agent for community acquired pneumonia,
      bacteremia, acute otitis media, and meningitis. Recent emergence of multi-drug
      resistant clinical isolates prompts the need of effective vaccine for the
      prevention of disease. The licensed polysaccharide-based pneumococcal vaccines
      only elicit protective antibodies against the infection of serotypes that are
      included in the vaccine. To broaden the protection, the use of pneumococcal
      proteins will be a feasible and preferable alternative. This communication
      provides a review on the biochemical properties of these protein candidates,
      their immunization results in animal studies, and perspectives on the development
      of protein-based pneumococcal vaccine.

PMID- 16893752
TI  - Amino acid catabolic pathways of lactic acid bacteria.
AB  - Lactic acid bacteria (LAB) constitute a diverse group of Gram positive obligately
      fermentative microorganisms which include both beneficial and pathogenic strains.
      LAB generally have complex nutritional requirements and therefore they are
      usually associated with nutrient-rich environments such as animal bodies, plants
      and foodstuffs. Amino acids represent an important resource for LAB and their
      utilization serves a number of physiological roles such as intracellular pH
      control, generation of metabolic energy or redox power, and resistance to stress.
      As a consequence, the regulation of amino acid catabolism involves a wide set of
      both general and specific regulators and shows significant differences among LAB.
      Moreover, due to their fermentative metabolism, LAB amino acid catabolic pathways
      in some cases differ significantly from those described in best studied
      prokaryotic model organisms such as Escherichia coli or Bacillus subtilis. Thus,
      LAB amino acid catabolism constitutes an interesting case for the study of
      metabolic pathways. Furthermore, LAB are involved in the production of a great
      variety of fermented products so that the products of amino acid catabolism are
      also relevant for the safety and the quality of fermented products.

PMID- 16893753
TI  - Topical vasodilators for preventing radial artery spasm during harvesting for
      coronary revascularization: comparison of 4 agents.
AB  - BACKGROUND: There is still controversy about which vasodilator solution is best
      for storing radial artery (RA) conduits prior to coronary artery bypass grafting.
      The aim of this pilot study was to investigate how 4 different topical
      vasodilators applied during RA harvesting affect blood flow with the vessel in
      situ. MATERIALS AND METHODS: The subjects were 85 patients who underwent RA
      harvesting in preparation for coronary artery bypass grafting. Each case was
      assigned to 1 of 5 groups (17 RAs each) that were treated with different
      solutions: normal saline (control), nitroglycerin, diltiazem, papaverine, and
      adenosine. Standard clinical concentrations were used. The RA was partially
      harvested (pedicle attached proximally) and flow rates and hemodynamic parameters
      (mean arterial pressure, heart rate, central venous pressure) were recorded at 2
      time points: (1) pretreatment and (2) after 5 minutes of immersion in 60 mL of
      treatment solution. Results were compared within and between groups, and post
      treatment-to-pretreatment ratios were calculated for each variable. RESULTS:
      There were no significant differences among the groups' mean pretreatment flow
      rates (P = .979) or mean posttreatment flow rates (P = .069). All except the
      diltiazem group showed a significant rise in mean flow rate from pretreatment to
      posttreatment. The mean posttreatment-to-pretreatment ratios for RA flow rate
      were 1.28 +/- 0.39 in the saline group, 1.85 +/- 0.72 in the nitroglycerin group,
      1.31 +/- 0.48 in the diltiazem group, 1.37 +/- 0.64 in the papaverine group, and
      1.23 +/- 0.42 in the adenosine group. Only the mean flow ratio in the
      nitroglycerin group was significantly higher than that in the saline group (P =
      .003). The mean flow ratios in the other vasodilator groups were not
      statistically different from the flow ratio in the saline group. CONCLUSIONS:
      These preliminary results indicate that topical application of nitroglycerin
      solution effectively prevents perioperative spasm of the RA in patients
      undergoing coronary artery bypass surgery. The authors recommend this solution
      for preparation and storage of RA grafts. Randomized controlled trials with power
      analysis will give more definitive information.

PMID- 16893754
TI  - Coronary revascularization in patients with obstructive sleep apnea syndrome.
AB  - BACKGROUND: There is a paucity of clinical information regarding therapy for
      ischemic heart disease (IHD) in patients with obstructive sleep apnea syndrome
      (OSAS). We evaluated our experience with surgical revascularization in this
      subset of patients. METHODS: Between January 1998 and April 2001, 20 patients
      with OSAS underwent isolated coronary artery bypass grafting (CABG). Outcomes
      were compared to a matched control group consisting of 65 patients. RESULTS:
      Patients with OSAS and the controls were similar with regard to age (65.8 years
      versus 65.2 years), ejection fraction (44.5% versus 46.9%), and systolic blood
      pressure (141 mmHg versus 142 mmHg). However, they were comparatively heavier
      (212 lb versus 188 lbs, P < .03), had higher pulmonary artery pressures (42 mmHg
      versus 34 mmHg, P < .001), higher pulmonary capillary wedge pressures (17 mmHg
      versus 14 mmHg, P < .01), higher left ventricular end diastolic pressures (20
      mmHg versus 18 mmHg, P < .04), and a greater incidence of diabetes (55% versus
      30%, P = .049). Patients with OSAS were more likely to require prolonged
      ventilation (40% versus 0%, P < .001) and tracheostomy (10% versus 0%, P = .01)
      and have a protracted intensive care unit (ICU) course (9 days versus 3 days, P =
      .002) and hospitalization (24 versus 13, P = .003). There were no peri-operative
      deaths, and both groups had significant improvement in angina and functional
      class. At a mean follow-up of 59 months, angina recurrence was 10% and survival
      was 95% in patients with OSAS. CONCLUSION: Patients with OSAS and IHD requiring
      coronary revascularization have substantial risk for pulmonary morbidity that
      impacts the duration of hospitalization but not mortality. Good symptom control
      and early to mid-term survival may be achieved in this subset of patients with
      aggressive peri-operative management of their OSAS.

PMID- 16893756
TI  - Simultaneous coronary artery bypass grafting and ascending aorta to bifemoral
      bypass for ischemic heart disease combined with critical leg ischemia: case
      reports.
AB  - Coronary artery disease may coexist with aortoiliac occlusive disease, and
      concomitant revascularization procedures may be required. The ascending aorta may
      be used as the source of inflow to both the femoral and coronary arteries in
      patients who present with coronary artery disease and critical leg ischemia. We
      present here 2 patients in whom coronary artery bypass grafting and ascending
      aorta-to-bifemoral bypass operations were performed simultaneously.

PMID- 16893755
TI  - Aorto-carotid bypass for cerebral malperfusion after aortic dissection surgery: a
      case report.
AB  - Malperfusion syndrome may complicate the postoperative course in patients who
      have undergone surgery for aortic dissection. In these cases, open surgery or
      endovascular intervention may be required. We present a case of postoperative
      onset of intermittent severe neurological symptoms after surgery for type A
      aortic dissection. Progressive dissection of the carotid arteries was diagnosed,
      and treatment options were discussed. A successful aorto-carotid bypass was
      performed by cardiac and vascular surgeons in collaboration. All neurological
      symptoms were completely resolved. We advocate a high degree of vigilance for
      signs of cerebral malperfusion in the intensive care unit. Early intervention can
      result in a successful outcome, as illustrated by this case report.

PMID- 16893757
TI  - Should UNOS Status 2 patients undergo transplantation?
AB  - BACKGROUND: With recent improvements in medical and device therapy, the benefit
      of cardiac transplantation for UNOS Status 2 patients has been questioned. No
      randomized trial has been performed to compare transplantation versus
      contemporary medical therapy. METHODS: Between January 1996 and December 2003,
      203 patients were listed at our institution for heart transplantation as UNOS
      Status 2. We performed a retrospective review to determine outcomes in these
      patients. RESULTS: Demographics of this cohort revealed a mean age of 52 years,
      female sex in 28%, and ischemic etiology in 47%. Eighty-one patients (40%) had an
      implantable cardiac defibrillator. A total of 64 patients (32%) had to be
      upgraded in their UNOS status, with 9 requiring a left ventricular assist device.
      Of the entire group, 95 (47%) underwent transplantation at a mean time of 303
      days, 45 (22%) died while waiting at a mean time of 397 days, and 24 (12%) were
      removed from the waiting list due to deterioration in medical condition such that
      transplantation was no longer an option. The remaining patients continue to wait
      or have been removed from consideration due to improved condition. Survival at 1-
      and 3-years postlisting was 94% and 87% for patients who received transplants
      compared to 81% and 57% for patients who did not receive transplants (P < .01).
      CONCLUSION: A significant number of patients listed as Status 2 are upgraded in
      UNOS status or die while on the waiting list. Early and midterm survival is
      significantly better with transplantation. Identification of variables associated
      with deterioration may allow for better risk stratification in the future. At
      this point, transplantation offers the best outcome.

PMID- 16893758
TI  - Fructose-1,6-bisphosphate supports cerebral energy metabolism in pigs after
      ischemic brain injury caused by experimental particle embolization.
AB  - BACKGROUND: Fructose-1,6-bisphosphate (FDP) is a high-energy intermediate that
      enhances glycolysis, preserves cellular adenosine triphosphate stores, and
      prevents the increase of intracellular calcium in ischemic tissue. Since it has
      been shown to provide metabolic support to the brain during ischemia, we planned
      this study to evaluate whether FDP is neuroprotective in the setting of combining
      hypothermic circulatory arrest (HCA) and irreversible embolic brain ischemic
      injury. METHODS: Twenty pigs were randomly assigned to receive 2 intravenous
      infusions of either FDP (500 mg/kg) or saline. The first infusion was given just
      before a 25-minute period of HCA and the second infusion immediately after HCA.
      Immediately before HCA, the descending aorta was clamped and 200 mg of albumin
      coated polystyrene microspheres (250-750 mm in diameter) were injected into the
      isolated aortic arch in both study groups. RESULTS: There were no significant
      differences between the study groups in terms of neurological outcome. Brain
      lactate/pyruvate ratio was significantly lower (P = .015) and brain pyruvate
      levels (P = .013) were significantly higher in the FDP group compared with
      controls. Brain lactate levels were significantly higher 8 hours after HCA (P =
      .049). CONCLUSION: The administration of FDP before and immediately after HCA
      combined with embolic brain ischemic injury was associated with significantly
      lower brain lactate/pyruvate ratio and significantly higher levels of brain
      pyruvate, as well as lower lactate levels 8 hours after HCA. FDP seems to protect
      the brain by supporting energy metabolism. The neurological outcome was not
      improved, most likely resulting from the irreversible nature of the microsphere
      occlusion.

PMID- 16893759
TI  - Mechanisms of insulin resistance in hypertensive rats.
AB  - Insulin resistance and hyperinsulinemia are common findings in patients with
      essential hypertension. Recent evidence indicates that these impairments in
      glucose metabolism may play a role not only in the development of type 2
      diabetes, but also in the onset and persistence of hypertension, dyslipidemia,
      and abdominal obesity. The accumulation of these risk factors constitutes a high
      risk group of cardiovascular diseases, the so-called metabolic syndrome. Insulin
      resistance has also been reported in several animal models for hypertension,
      including the spontaneously hypertensive rat (SHR) and the fructose-fed rat
      (FFR). SHRs and FFRs have been employed in many studies to investigate the
      mechanisms and pathophysiology of insulin resistance and hypertension, but the
      precise mechanism of insulin resistance remains to be clarified. In this review,
      the possible mechanisms of insulin resistance in SHRs and FFRs are summarized.

PMID- 16893768
TI  - Sorption and desorption behavior of chloroanilines and chlorophenols on
      montmorillonite and kaolinite.
AB  - The bioavailability of pollutants, pesticides and/or their degradation products
      in soil depends on the strength of their sorption by the different soil
      components, particularly by the clay minerals. This study reports the sorption
      desorption behavior of the environmentally hazardous industrial pollutants and
      certain pesticides degradation products, 3-chloroaniline, 3,4-dichloroaniline,
      2,4,6-trichloroaniline, 4-chlorophenol, 2,4-dichlorophenol and 2,4,6
      trichlorophenol on the reference clays kaolinite KGa-1 and Na-montmorillonite SWy
      l. In batch studies, 2.0 g of clay were equilibrated with 100.0 mL solutions of
      each chemical at concentrations ranging from 10.0 to 200.0 mg/L. The uptake of
      the compounds was deduced from the results of HPLC-UV-Vis analysis. The
      lipophilic species were best retained by both clay materials. The most lipophilic
      chemical used in the study, 2,4,6-trichloroaniline, was also the most strongly
      retained, with sorption of up to 8 mg/g. In desorption experiments, which also
      relied on HPLC-UV-Vis technique, 2,4,6-trichloroaniline was the least desorbed
      from montmorillonite. However, on kaolinite all of the compounds under study were
      irreversibly retained. The experimental data have been modelled according to the
      Langmuir and Freundlich isotherms. A hypothesis is proposed concerning the
      sorption mechanism and potential applications of the findings in remediation
      strategies have been suggested.

PMID- 16893769
TI  - Bioassay for determining sensitivity to sulfosulfuron on seven plant species.
AB  - This study presents a bioassay procedure, based on the root and shoot growth
      parameters, for the determination of the herbicide sulfosulfuron (1-(4,6
      dimethoxypyrimidin-2-yl)-3-(2-ethylsulfonylimidazo[1,2-a]pyridin-3
      ylsulfonil)urea) sensitivity on seven vegetal species. Plant response to
      sulfosulfuron was calculated with the equations fitted to the root growth data as
      a function of the logarithm of the herbicide concentration by non-linear
      regression and was used to calculate the doses for 10, 30 and 50% inhibition of
      root growth (EC10, EC30 and EC50). The results indicate that the phytotoxic
      effect of sulfosulfuron in all the species assayed followed the order: flax >
      maize > onion > vetch > lepidium sativum > tomato > barley. These species showed
      phytotoxicity at low levels of sulfosulfuron and flax appeared to be the most
      susceptible species to sulfosulfuron (0.001 mg/L).

PMID- 16893770
TI  - Degradation of metribuzin in two soil types of Lebanon.
AB  - The degradation of metribuzin [4-amino-6-tert-butyl-3-methylthio-1,2,4-triazin
      5(4H)-one] as influenced by soil type, temperature, humidity, organic
      fertilizers, soil sterilization, and ultra-violet radiation was studied in two
      soil types of Lebanon under laboratory conditions. The two soil types were sandy
      loam and clay. Deamination of metribuzin in the sandy loam soil to its
      deaminometribuzin (DA) derivative was basically a result of biological activity.
      In the clay soil the first metabolite diketometribuzin (DK) was a result of
      oxidative desulfuration, while diketo-deaminometribuzin (DADK) was the product of
      reductive deamination. The two soils represented major differences in the
      pesticide transformation processes. Photodecomposition on the soil surface and in
      aqueous media was also an important process in the degradation of metribuzin.
      Furthermore, the increase in soil organic matter enhanced degradation.

PMID- 16893771
TI  - Development of an in-line system for the analysis of 4,4'-DDT in water.
AB  - An in-line system for trace persistent organic pollutants (POPs) in water was
      developed by using a laboratory-made hollow fiber membrane (HFM) unit connected
      with a high-resolution gas chromatograph-mass spectrometer (HRGC-MS). The
      semivolatile organic compound, 4,4'-Dichlorodiphenyl trichloroethane (4,4'-DDT),
      was chosen as a representative of a persistent organic compound. The synthetic
      water contaminated with 4,4'-DDT was passed through the HFM unit, the extraction
      occurred by the analyte pervaporated and permeated, then stripped into HRGC-MS.
      Several factors were investigated for the high extraction efficiency. The best
      performance was obtained at sample and stripping gas flow rates of 6 and 9 mLmin
      1, respectively, and desorption temperature of 60 degrees C. At this temperature,
      the diffusion rate was enhanced by 15 times over 25 degrees C. A wide linear
      dynamic range was obtained, i.e., 0.10-1.0 mgL-1, with a limit of detection (LOD)
      of 90 microgL-1. The extraction efficiency of 4,4'-DDT in real water samples was
      in the range of 83-94%. Real water samples were analyzed and 0.6 microgL-1 of
      4,4'-DDT was found in unregistered bottled water and 7.0 microgL-1 in tap water.

PMID- 16893773
TI  - Pyrimethanil residues on table grapes Italia after field treatment.
AB  - Residues of the pyrimidine fungicide pyrimethanil [N-(4,6-dimethylpyrimidin
      2yl)aniline] were determined in table grapes "Italia" by gas chromatography
      nitrogen-phosphorus detector (GC-NPD). Pesticides were extracted from grapes with
      ethyl acetate and hexane solution (1:1 v/v), and were analyzed without any
      further clean up. Pyrimethanil was confirmed by high-performance liquid
      chromatography (HPLC) fitted with a diode array detector (DAD) and electrospray
      ionization mass spectrometry (ESI-MS) in the select ion-monitoring mode (SIM).
      The residue of pyrimethanil was under the legal limit immediately after
      treatment, and showed a half-life time, calculated as a reaction of pseudo first
      order, of 12 days, with a regression coefficient of 0.9954. Recoveries from
      fortified grapes ranged between 90 and 113% with a maximum coefficient of
      variation (CV) of 11%. The calculated limits of detection and quantitation for
      pyrimethanil were 0.005 and 0.01 mg/kg, respectively.

PMID- 16893772
TI  - Variations of bacterial community structure in flooded paddy soil contaminated
      with herbicide quinclorac.
AB  - The denaturing gradient gel electrophoresis (DGGE) method was applied to
      determine the relative genetic complexity of microbial communities in flooded
      paddy soil treated with herbicide quinclorac (3,7-dichloro-8-quinoline-carboylic
      acid). The results obtained showed a significant effect of quinclorac on the
      development of bacterial populations in soils contaminated with different
      concentrations of the herbicide at the early time after application. In general,
      however, the number of populations of the same soil sample treated with the same
      concentration of the quinclorac differed obviously with increasing incubation
      time within the early 8 weeks. The scale of differences in banding patterns
      showed that the microbial community structures of the quinclorac-treated and non
      quinclorac-treated soils were not significantly different after 21 weeks of
      incubation. Quantification, as demonstrated in this paper, was studied by
      establishing dose-response relationships. Significant pattern variations were
      quantified. Prominent DGGE bands were excised, cloned and sequenced to gain
      insight into the identities of predominant bacterial populations. The majority of
      DGGE band sequences were related to bacterial genera Clostridium,
      Sphingobacterium, Xanthomonas and Rhodococcus.

PMID- 16893774
TI  - Micronuclei frequency in lymphocytes and antioxidants in the blood of traditional
      limited-resource farm workers exposed to pesticides.
AB  - Chronic low-level exposure to synthetic pesticides is implicated in many health
      conditions that result from the induction of oxidative stress, including
      cytogenetic damage. The objective of this study was to assess the risk of
      genotoxicity using micronuclei (MN) formation in lymphocytes and to determine
      changes in blood antioxidants superoxide dismutase (SOD) in erythrocytes (E) and
      glutathione (GSH) in E and plasma (PL) in farm workers for six months during a
      growing season. Blood and urine samples were collected once a month for six
      months (June to November 2003) from farm workers (n = 15) and urban unexposed
      controls (n = 10). Lymphocytes from blood were separated by density gradient
      centrifugation using Histopaque and cultured using the standard technique. There
      was no significant difference in the cytokinesis blocked proliferation index
      (CBPI) of lymphocytes between the farm workers and the control group, but there
      was a 76% increase in average MN frequency in lymphocytes of the farm worker
      group (P <or= 0.05). In addition, MN frequency peaked during August as compared
      to the other months and the controls (P <or= 0.05). An 18% decline was observed
      in the activity of E-SOD in the farm worker group (P <or= 0.05). GSH in E and PL
      were similar in both groups. These data suggest that the farm workers may be at a
      greater risk of developing genotoxicity due to continued exposure to pesticides,
      especially during the intensive growing season.

PMID- 16893775
TI  - Triazine and metolachlor herbicide residues in farm areas of the Lower Fraser
      valley, British Columbia, Canada.
AB  - Crop soils, ditch sediments and water flowing from several Lower Fraser River
      (LFR) farm areas of British Columbia, Canada, to salmon tributary streams of that
      river were sampled in 2004-2005 to quantify for residues of triazine [atrazine,
      desethylatrazine (a transformation product of atrazine), propazine, and simazine]
      and metolachlor (a chloroacetamide) herbicides. Average concentrations [microg kg
      1 dry weight (d.w.)] of triazine (10,110) and metolachlor (8,910) herbicides
      detected in crop soils at the start (May 2004, 2005) of the growing season were
      about 17 and 6 times, respectively, higher than those found for both herbicide
      groups during (June-Sept, 2004, 2005) the growing season. In contrast, mean
      concentrations (microg L-1) of triazines (0.092) and metolachlor (0.014) in
      permanent ditches adjacent to farms were about 7 and 28 times, respectively,
      lower at the start than during the growing season. Both herbicide groups in ditch
      sediments were detected only during the growing season at concentrations
      averaging about 315 microg kg-1 d.w. The risk potential of these herbicides for
      non-target aquatic organisms inhabiting permanent farm ditches contiguous to
      tributary streams of the LFR during the growing season is evaluated and
      discussed.

PMID- 16893776
TI  - Azinphos methyl residues in shallow groundwater from the fruit production region
      of northern Patagonia, Argentina.
AB  - Groundwater samples were collected from monitoring wells along an area of
      intensive fruit production. Different types of correlations were investigated
      between soil physicochemical characteristics, depths and agricultural practices
      with pesticide detection frequency. In the three analyzed periods azinphos
      methyl, S-(3,4-diydro-4-oxobenzo[d]-[1,2,3]-triazin-3-ylmethyl)-O,O-dimethyl
      phosphorodithioate, showed a definite seasonal behavior related to the
      application pattern, increasing its concentration in the aquifer from October to
      November-December and then decreasing towards March. Samples obtained during the
      non-spraying season showed that azinphos methyl residues were lower than
      detection limit (LOD). An inverse correlation was observed between azinphos
      methyl concentration and the time elapsed since the last pesticide application.
      Seasonal events such as rain and irrigation influence the chemical concentration
      in the well, while no correlation was obtained between soil characteristics and
      azinphos methyl concentration. The soil attenuation capacity was not enough to
      prevent the presence of azinphos methyl in the aquifer during the application
      season.

PMID- 16893777
TI  - Behavior of two phenyl urea herbicides in clayey soils and effect of alternating
      dry-wet conditions on their availability.
AB  - Adsorption and mobility of linuron (3-(3,4-dichlorophenyl)-1-methoxy-1
      methylurea) and diuron (3-(3,4-dichlorophenyl)-1, 1-dimethylurea) were studied in
      clayey soils from the Gharb area (Morocco). Soils A and B were planted with sun
      flower (Helianthus annuus) while soil C was planted with sugar cane (Saccharum
      offcinarum). Adsorption was studied for linuron in soils A and B, while mobility
      was studied only in soil B. Adsorption data were found to fit the Freundlich
      equation with correlation coefficients r2 > 0.9. Freundlich coefficients (Kf, nf)
      were in agreement with L and S isotherm types for soils A and B, respectively.
      Values of Koc (195 and 102) indicate moderate adsorption. Desorption isotherms
      for linuron showed hysteresis for both soils. The pesticide would be more bound
      to soil A (H = 8.44) than to soil B (H = 4.01). The effect of alternating wet and
      dry conditions was tested for soils A and B. Results showed that retention would
      increase in soil subject to an additional wet and dry cycle. In the case of
      diuron isotherm was of type L in soil C. Desorption was noticeable at high
      concentrations and tended to decrease when concentrations diminished. Mobility of
      linuron was tested in polyvinyle chloride (PVC) columns, which received different
      treatments before their percolation. The pesticide was more mobile in a
      previously saturated column. In columns subject to a drying step after saturation
      with water, linuron mobility was greatly reduced.

PMID- 16893778
TI  - Biodegradation of endosulfan by a soil bacterium.
AB  - A bacterium capable of metabolizing endosulfan (6,7,8,9,10,10-hexachloro
      1,5,5a,6,9,9a-hexahydro-6,9-methano-2,4,3-benzodioxathiepine3-oxide) was isolated
      from cotton-growing soil and effectively shown to degrade endosulfan into
      endosulfan sulfate. The bacterium degraded 50% of the compound within 3 days of
      incubation. Endosulfan sulfate was the only terminal product and no other
      metabolites were formed during the incubation. Endosulfan and its metabolites
      were analyzed by gas chromatography. The metabolites formed indicated that the
      organism follows an oxidative pathway for metabolism of this pesticide.
      Therefore, the present study, microbial degradation of endosulfan by a soil
      bacterium, may provide a basis for the development of bioremediation strategies
      to remediate the pollutants in the environment.

PMID- 16893779
TI  - Sorption and desorption of three endocrine disrupters in soils.
AB  - Sorption of the estrogens estrone (E1), 17beta-estradiol (E2) and 17alpha
      ethynylestradiol (EE2) on four soils was examined using batch equilibrium
      experiments with initial estrogen concentrations ranging from 10 to 1000 ng mL-1.
      At all concentrations, >85% of the three estrogens sorbed rapidly to a sandy
      soil. E1 sorbed more strongly to soil than E2 or EE2. Partial oxidation of E2 to
      E1 was observed in the presence of soils. Autoclaving was more effective at
      reducing this conversion than inhibition with sodium azide or mercuric chloride,
      and had little effect on sorption, relative to the chemical microbial inhibitors.
      Sorption of EE2 was greater for fine-textured than coarse-textured soils, but
      greater than 90% of EE2 sorbed onto all four soils. The greatest degree of
      desorption of estrogens from the sandy soil occurred with the lowest initial
      concentration of 10 ng mL-1 and reached levels >or=80% for E1 and E2. Desorption
      of EE2 was greater in coarser textured soils than finer-textured soils. Again,
      relative desorption from all soils was greatest with low initial concentrations.
      Therefore, at environmentally relevant concentrations, estrogens quickly sorb to
      soils, and soils have a large capacity to bind estrogens, but these endocrine
      disrupting compounds can become easily desorbed and released into the aqueous
      phase.

PMID- 16893780
TI  - Influence of agricultural antibiotics and 17beta-estradiol on the microbial
      community of soil.
AB  - Agricultural pharmaceuticals are a major environmental concern because of their
      hazardous effects on human and wildlife. This study analyzed phospholipid ester
      linked fatty acids (PLFAs) and quinones to investigate the effects of a steroid
      (17beta-estradiol) and agricultural antibiotics (chlortetracycline and tylosin)
      on soil microbes in the laboratory. Two different types of soil were used:
      Sequatchie loam (0.8% organic matter) and LaDelle silt loam (9.2% organic
      matter). The soils were spiked with 17beta-estradiol and antibiotics, alone or in
      combination. In Sequatchie loam, 17beta-estradiol significantly increased the
      microbial biomass, especially the biomarkers for beta proteobacteria
      (16:1omega7c, 18:1omega7c, Cy17:0, and UQ-8). The coexistence of antibiotics
      decreased the stimulatory effect of 17beta-estradiol on the microbial community.
      In LaDelle silt loam, there were no significant differences in total microbial
      biomass and their microbial community structure among the treatments. Overall,
      17beta-estradiol changed the microbial community of soil and the presence of
      antibiotics nullified the effect of 17beta-estradiol. However, the effects of
      17beta-estradiol and antibiotics on soil microbes were sensitive to the soil
      properties, as seen in the LaDelle silt loam.

PMID- 16893782
TI  - Bioefficacy of iprodione against two desapers, its compatibility with T.
      harzianum and residues on cabbage crop.
AB  - Iprodione (3-(3,5-dichlorophenyl)-N-isopropyl-2,4-dioxoimidazolidine-1
      carboxamide) bio-assayed against fungi Alternaria brassicicola and Sclerotinia
      sclerotiorum was found to be highly effective for inhibiting these desapers.
      Inhibition of A. brassicicola was 100% up to the dose of 75 ppm and for S.
      sclerotiorum there was 50% inhibition for the same concentration. Formulation of
      the pesticide was applied @ 500 and 1000 g. a.i./ha on the cabbage crop grown in
      the fields. Residues in the edible sample of cabbage were analyzed by gas
      choromatography for the fungicide and its metabolites. The dissipation of
      residues of the fungicide and its bio-efficacy against two fungi are presented.
      It dissipated from 3.72 to 0.072 microg/g on cabbage head by 15 days after
      treatment. The EC50 values of iprodione were found to be 11.5 ppm and 79.4 ppm
      for A. brassicicola and S. sclerotiorum, respectively. Half-life of iprodione was
      found to be 3 days for both cabbage head and leaves. The compatibility of the
      fungicide with a bio agent, T. harzianum was also studied and these two were not
      found to be compatible.

PMID- 16893781
TI  - Degradation of carbofuran in water by solar photocatalysis in presence of
      photosensitizers.
AB  - The effect of the presence of photosensitizers, methylene blue (MB) and rose
      Bengal (RB), on the degradation of carbofuran (2,3-dihydro-2,2-dimethylbenzofuran
      7-yl methylcarbamate) in water in a solar photocatalytic system was investigated.
      It was found that as compared to MB, RB generally showed a stronger effect on the
      decomposition of carbofuran under comparable conditions. Among the conditions
      studied, adding 2 x 10(-6) M of RB, that corresponding to 2% of the initial
      concentration of carbofuran solution in the system, rendered the most effective
      degradation of carbofuran. As a result, a carbofuran removal percentage of 69.9%,
      a mineralization efficiency of 28.0%, and a microtoxicity reduction of 65.0%
      could be achieved. The degradation and mineralization of carbofuran was found to
      follow the pseudo-first order reaction kinetics. The decomposition mechanism of
      carbofuran was further investigated through identification of the intermediates
      to elaborate the influence of dye photosensitizer on the solar photocatalysis of
      carbofuran in water. On the basis of the intermediates identified, including
      carbofuran phenol, 3-hydroxy carbofuran phenol, and substituted alcohols (3
      phenoxy 1-propanol, 2-ethyl 1-hexanol, 2-butoxyl ethanol), it appears that
      hydrolysis and hydroxylation were the two key mechanisms for decomposing
      carbofuran during the process of solar photocatalysis with the aid of dye
      photosensitizer.

PMID- 16893783
TI  - Effect of monosodium methanarsonate application on cuticle wax content of
      cocklebur and cotton plants.
AB  - Leaf cuticle waxes were extracted from monosodium methanearsonate (MSMA)
      resistant (R) and -susceptible (S) common cocklebur (Xanthium strumarium L.) and
      cotton (Gossypium hirsutum L.) plants at 0, 3, 5, and 7 days after treatment
      (DAT) following 1x and 2x MSMA applications. Wax constituents were analyzed by
      gas chromatography (GC) with flame ionization detection and compared to alkane
      and alcohol standards of carbon lengths varying from C21 to C30. Differences in
      waxes were calculated and reported as change per ng mm2-1. Tricosane (C23) was
      found to increase following MSMA applications. All other alkanes decreased by 7
      DAT, with some showing a linear effect over time in the R-cocklebur. Alcohol
      constituents were also observed to decrease by 7 DAT. Total arsenic in the
      extracted wax fraction was determined, with greatest quantities detected in the R
      cocklebur. Wax changes are not believed to play a role in cotton tolerance, since
      changes in cuticle concentrations were minimal. Cocklebur resistance to MSMA is
      not due to cuticle constituents; the wax changes are a secondary effect in
      response to herbicide application.

PMID- 16893784
TI  - Phototransformation of alphacypermethrin as thin film on glass and soil surface.
AB  - Photodegradation of alphacypermethrin ((RS)-alpha cyano-3-phenoxy benzyl (1RS)
      cis-3-(2,2,dichlorovinyl)-2,2-dimethyl cyclopropane carboxylate) was studied as a
      thin film on glass surface and on black and red soil surfaces. A number of
      photoproducts from glass surfaces have been isolated, characterized and
      identified by gas chromatography-mass spectroscopy (GC-MS). However, only two of
      them viz. 3-phenoxy benzyl alcohol and [2,2-dichlorovinyl-3(2,2,dimethyl)
      cyclopropane carboxylate] could be identified from both the soil. Rate of
      photodegradation on glass and soil surface under UV and sunlight followed first
      order kinetics with significant correlation coefficients. The rate of
      photodegradation was greater on black than on red soil.

PMID- 16893785
TI  - Composition of aqueous extracts of broiler litter treated with aluminum sulfate,
      ferrous sulfate, ferric chloride and gypsum.
AB  - More knowledge on the composition of aqueous extracts of broiler litter amended
      for Water Soluble P (WSP) reduction would help to understand how amendments work.
      We measured pH, concentrations of Ca, Mg, Fe, Al, Cu, Mn, Zn, Molybdate Reactive
      P (MRP), and Dissolved Unreactive P (DUP) in water extracts of broiler litter
      treated with aluminum sulfate (ALS), ferrous sulfate (FES), ferric chloride
      (FEC), and gypsum (GYP) at 0, 5, 15, and 25% w/w. In order to study the effects
      of acidification, the same properties were measured in aqueous extracts of
      broiler litter suspensions that were titrated to end-points 3, 4, or 6 with 0.5N
      HCl. Concentrations of MRP, DUP, Ca and Mg, were 61%, 53%, 3.8 times, and 2.6
      times greater in extracts from suspensions acidified to pH 6 than at the original
      pH of 8.9. ALS, FES, and FEC reduced pH, and showed similar effects on WSP
      concentrations, which were greater than with GYP. The magnitude of the reductions
      in WSP by ALS, FES, and FEC is uncertain because the actual amount of WSP
      immobilized cannot be determined. This is because of two opposite effects: 1)
      Through adsorption, soluble aluminum and iron remove phosphates from solution,
      and 2) Through acidification, iron and aluminum compounds release phosphates to
      solution.

PMID- 16893786
TI  - Moist olive husks addition to a silty clay soil: influence on microbial and
      biochemical parameters.
AB  - To investigate the effects of moist olive husks (MOH-residues) on soil
      respiration, microbial biomass, and enzymatic (o-diphenoloxidase, beta
      glucosidase, dehydrogenase and alkaline phosphatase) activities, a silty clay
      soil was incubated with 0 (control), 8 x 10(3) (D), 16 x 10(3) (2D) and 80 x
      10(3) (10D) kg ha-1 of MOH-residues on a dry weight basis. Soil respiration and
      microbial biomass data indicated that the addition of MOH-residues strongly
      increased microbial activity proportionally to the amounts added. Data of qCO2
      suggested that the respiration to biomass ratio of the microbial population was
      strongly modified by MOH-residues additions during the first 90 days of
      incubation. The qCO2 data suggested a low efficiency in energy yields from C
      oxidation during the first 2 months of soil incubation. qFDA seemed to be
      relatively unaffected for treatments D and 2D as compared to the control, but was
      significantly lowered by the application of 10D, showing the lowest hydrolytic
      activity of microbial biomass in this treatment up to 360 days of incubation. o
      Diphenoloxidase activity was delayed, and this delay was extended with the
      addition of larger quantities of MOH-residues. Alkaline phosphatase, beta
      glucosidase and dehydrogenase activities were in line with the findings on
      microbial biomass changes and activities. The biological and biochemical data
      suggest that the addition of a large quantity of MOH-residues (80 x 10(3) kg ha
      1) strongly modifies the soil characteristics affecting the r- and K-strategist
      populations, and that these changes last for at least the 360 days of incubation.
      The data also suggest that application rates exceeding 16 x 10(3) kg ha-1 are not
      recommended until the agro-chemical and -physical functions of the soil are
      further studied.

PMID- 16893788
TI  - Introduction.

PMID- 16893789
TI  - Control of chaos: methods and applications in mechanics.
AB  - A survey of the field related to control of chaotic systems is presented. Several
      major branches of research that are discussed are feed-forward ('non-feedback')
      control (based on periodic excitation of the system), the 'Ott-Grebogi-Yorke
      method' (based on the linearization of the Poincare map), the 'Pyragas method'
      (based on a time-delayed feedback), traditional for control-engineering methods
      including linear, nonlinear and adaptive control. Other areas of research such as
      control of distributed (spatio-temporal and delayed) systems, chaotic mixing are
      outlined. Applications to control of chaotic mechanical systems are discussed.

PMID- 16893787
TI  - Elemental uptake by seaweed, Plocamium corallorhirza along the Kwazulu-natal
      coast of Indian Ocean, South Africa.
AB  - This study reports the elemental uptake by Plocamium corallorhiza, a Rhodophyta
      class of coralline alga grown richly along KwaZulu-Natal coastline. The uptake of
      seven important elements, namely Fe, Mn, As, B, Ti, Zn and Hg, selected based on
      their abundance in the samples, were investigated for a one-year cycle, from June
      2002 to May 2003, at four chosen sites located along the KwaZulu-Natal coastline.
      The sites spread over 150 km from North to South Coast are Zinkwasi, Ballito,
      Treasure Beach and Park Rynie. P. corallorhiza possess good manganese and arsenic
      accumulating ability and has potential to be an excellent indicator for most of
      the metals studied. A typical P. corallorhiza sample at Park Rynie (winter)
      recorded Mn (14 ppm), Fe (6.02 ppm), As (8.4 ppm), B (1580 ppb), Zn (234 ppb), Ti
      (751 ppb) and Hg (15.8 ppb). The general trend found at all sites was a large
      decrease in iron concentration in spring and summer and increase in winter.
      Mercury uptake was lowest in winter and autumn at all sites. The highest mercury
      levels in the seaweeds were recorded during spring or summer.

PMID- 16893790
TI  - Delayed feedback control of chaos.
AB  - Time-delayed feedback control is well known as a practical method for stabilizing
      unstable periodic orbits embedded in chaotic attractors. The method is based on
      applying feedback perturbation proportional to the deviation of the current state
      of the system from its state one period in the past, so that the control signal
      vanishes when the stabilization of the target orbit is attained. A brief review
      on experimental implementations, applications for theoretical models and most
      important modifications of the method is presented. Recent advancements in the
      theory, as well as an idea of using an unstable degree of freedom in a feedback
      loop to avoid a well-known topological limitation of the method, are described in
      detail.

PMID- 16893791
TI  - Melnikov method approach to control of homoclinic/heteroclinic chaos by weak
      harmonic excitations.
AB  - A review on the application of Melnikov's method to control homoclinic and
      heteroclinic chaos in low-dimensional, non-autonomous and dissipative oscillator
      systems by weak harmonic excitations is presented, including diverse
      applications, such as chaotic escape from a potential well, chaotic solitons in
      Frenkel-Kontorova chains and chaotic-charged particles in the field of an
      electrostatic wave packet.

PMID- 16893792
TI  - Optimal control and anti-control of the nonlinear dynamics of a rigid block.
AB  - This paper deals with control and anti-control of overturning of a rigid block
      subjected to a generic periodic excitation. Attention is focused on two relevant
      thresholds, corresponding to heteroclinic bifurcation and immediate overturning,
      and representing lower and upper bounds of the region where toppling can occur.
      The two opposite problems of increasing (control) or decreasing (anti-control) of
      these two curves by properly modifying the shape of the excitation are
      investigated in depth and the optimal excitations permitting their maximum
      variations are determined. The notions of 'global' and 'one-side' control (anti
      control) are utilized and their different importance for the various cases is
      discussed. The effects of control (anti-control) of one curve on the uncontrolled
      (non-anti-controlled) curve are also investigated, both analytically and with
      numerical overturning charts. A good agreement is seen to occur.

PMID- 16893793
TI  - Controlling spatio-temporal chaos in the scenario of the one-dimensional complex
      Ginzburg-Landau equation.
AB  - We discuss some issues related with the process of controlling space-time chaotic
      states in the one-dimensional complex Ginzburg-Landau equation. We address the
      problem of gathering control over turbulent regimes with the use of only a
      limited number of controllers, each one of them implementing, in parallel, a
      local control technique for restoring an unstable plane-wave solution. We show
      that the system extension does not influence the density of controllers needed in
      order to achieve control.

PMID- 16893794
TI  - Minimal control synthesis adaptive control of nonlinear systems: utilizing the
      properties of chaos.
AB  - This paper discusses a novel approach to the control of chaos based on the use of
      the adaptive minimal control synthesis algorithm. The strategies presented are
      based on the explicit exploitation of different properties of chaotic systems
      including the boundedness of the chaotic attractors and their topological
      transitivity (or ergodicity). It is shown that chaos can be exploited to
      synthesize more efficient control techniques for nonlinear systems. For instance,
      by using the ergodicity of the chaotic trajectory, we show that a local adaptive
      control strategy can be used to synthesize a global controller. An application is
      to the swing-up control of a double inverted pendulum.

PMID- 16893795
TI  - Control of chaos in nonlinear systems with time-periodic coefficients.
AB  - In this study, some techniques for the control of chaotic nonlinear systems with
      periodic coefficients are presented. First, chaos is eliminated from a given
      range of the system parameters by driving the system to a desired periodic orbit
      or to a fixed point using a full-state feedback. One has to deal with the same
      mathematical problem in the event when an autonomous system exhibiting chaos is
      desired to be driven to a periodic orbit. This is achieved by employing either a
      linear or a nonlinear control technique. In the linear method, a linear full
      state feedback controller is designed by symbolic computation. The nonlinear
      technique is based on the idea of feedback linearization. A set of coordinate
      transformation is introduced, which leads to an equivalent linear system that can
      be controlled by known methods. Our second idea is to delay the onset of chaos
      beyond a given parameter range by a purely nonlinear control strategy that
      employs local bifurcation analysis of time-periodic systems. In this method,
      nonlinear properties of post-bifurcation dynamics, such as stability or rate of
      growth of a limit set, are modified by a nonlinear state feedback control. The
      control strategies are illustrated through examples. All methods are general in
      the sense that they can be applied to systems with no restrictions on the size of
      the periodic terms.

PMID- 16893796
TI  - Introduction to anti-control of discrete chaos: theory and applications.
AB  - In this paper, the notion of anti-control of chaos (or chaotification) is
      introduced, which means to make an originally non-chaotic dynamical system
      chaotic or enhance the existing chaos of a chaotic system. The main interest in
      this paper is to employ the classical feedback control techniques. Only the
      discrete case is discussed in detail, including both finite-dimensional and
      infinite-dimensional settings.

PMID- 16893797
TI  - Anti-control of chaos of single time-scale brushless DC motor.
AB  - Anti-control of chaos of single time-scale brushless DC motors is studied in this
      paper. In order to analyse a variety of periodic and chaotic phenomena, we employ
      several numerical techniques such as phase portraits, bifurcation diagrams and
      Lyapunov exponents. Anti-control of chaos can be achieved by adding an external
      constant term or an external periodic term.

PMID- 16893798
TI  - Control of chaos and its relevancy to spacecraft steering.
AB  - In 1990, a seminal work named controlling chaos showed that not only the chaotic
      evolution could be controlled, but also the complexity inherent in the chaotic
      dynamics could be exploited to provide a unique level of flexibility and
      efficiency in technological uses of this phenomenon. Control of chaos is also
      making substantial contribution in the field of astrodynamics, especially related
      to the exciting issue of low-energy transfer. The purpose of this work is to
      bring up the main ideas regarding the control of chaos and targeting, and to show
      how these techniques can be extended to Hamiltonian situations. We give realistic
      examples related to astrodynamics problems, in which these techniques are unique
      in terms of efficiency related to low-energy spacecraft transfer and in-orbit
      stabilization.

PMID- 16893799
TI  - Exploiting the controlled responses of chaotic elements to design configurable
      hardware.
AB  - We discuss how threshold mechanisms can be effectively employed to control
      chaotic systems onto stable fixed points and limit cycles of widely varying
      periodicities. Then, we outline the theory and experimental realization of
      fundamental logic-gates from a chaotic system, using thresholding to effect
      control. A key feature of this implementation is that a single chaotic
      'processor' can be flexibly configured (and re-configured) to emulate different
      fixed or dynamic logic gates through the simple manipulation of a threshold
      level.

PMID- 16893800
TI  - Phase space warping: nonlinear time-series analysis for slowly drifting systems.
AB  - A new general dynamical systems approach to data analysis is presented that
      allows one to track slowly evolving variables responsible for non-stationarity in
      a fast subsystem. The method is based on the idea of phase space warping, which
      refers to the small distortions in the fast subsystem's phase space that results
      from the slow drift, and uses short-time reference model prediction error as its
      primary measurement of this phenomenon. The basic theory is presented and the
      issues associated with its implementation in a practical algorithm are discussed.
      A vector-tracking version of the procedure, based on smooth orthogonal
      decomposition analysis, is applied to the study of a nonlinear vibrating beam
      experiment in which a crack propagates to complete fracture. Our method shows
      that the damage evolution is governed by a scalar process, and we are able to
      give real-time estimates of the current damage state and identify the governing
      damage evolution model. Using a final recursive estimation step based on this
      model, the time to failure is continuously and accurately predicted well in
      advance of actual failure.

PMID- 16893801
TI  - Structural health monitoring based on sensitivity vector fields and attractor
      morphing.
AB  - The dynamic responses of a thermo-shielding panel forced by unsteady aerodynamic
      loads and a classical Duffing oscillator are investigated to detect structural
      damage. A nonlinear aeroelastic model is obtained for the panel by using third
      order piston theory to model the unsteady supersonic flow, which interacts with
      the panel. To identify damage, we analyse the morphology (deformation and
      movement) of the attractor of the dynamics of the aeroelastic system and the
      Duffing oscillator. Damages of various locations, extents and levels are shown to
      be revealed by the attractor-based analysis. For the panel, the type of damage
      considered is a local reduction in the bending stiffness. For the Duffing
      oscillator, variations in the linear and nonlinear stiffnesses and damping are
      considered as damage. Present studies of such problems are based on linear
      theories. In contrast, the presented approach using nonlinear dynamics has the
      potential of enhancing accuracy and sensitivity of detection.

PMID- 16893802
TI  - Coexisting chaotic and periodic dynamics in clock escapements.
AB  - This paper addresses the nature of noise in machines. As a concrete example, we
      examine the dynamics of clock escapements from experimental, historical and
      analytical points of view. Experiments on two escapement mechanisms from the
      Reuleaux kinematic collection at Cornell University are used to illustrate
      chaotic-like noise in clocks. These vibrations coexist with the periodic dynamics
      of the balance wheel or pendulum. A mathematical model is presented that shows
      how self-generated chaos in clocks can break the dry friction in the gear train.
      This model is shown to exhibit a strange attractor in the structural vibration of
      the clock. The internal feedback between the oscillator and the escapement
      structure is similar to anti-control of chaos models.

PMID- 16893804
TI  - Theories on immigrant women's health.
AB  - Our purpose in this article is to review theories critically that have been used
      to explain immigrant women's health based on 4 case studies of Korean immigrant
      women's experiences in the United States and suggest directions for future
      development of theories on immigrant women's health. First, 3 existing theories
      on immigration and health (selective migration, negative effect of immigration,
      and acculturation) are concisely described. Then, the daily experiences of 4 low
      income Korean immigrant women are described in a narrative mode, and the 3
      existing theories are critiqued in terms of how they can explain the women's
      narratives. Finally, implications for future theory development on immigrant
      women's health experience are proposed based on the discussion.

PMID- 16893805
TI  - Help-seeking rates for intimate partner violence (IPV) among Canadian immigrant
      women.
AB  - We examined rates of help seeking for intimate partner violence (IPV) among
      recent (0-9 years in Canada) and non-recent (10+ years in Canada) immigrant
      women. Data from a national, cross-sectional, telephone survey were used. Help
      seeking variables included disclosure of IPV, reporting IPV to police, use of
      social services subsequent to IPV, and barriers to social service use. Recent
      immigrant women, compared with non-recent immigrant women, were significantly
      more likely to report IPV to police and less likely to use social services.
      Findings have important implications for prevention and detection of IPV in
      immigrant communities and in future research.

PMID- 16893806
TI  - Living "in-between"--Vietnamese Canadian women's experiences: implications for
      health care practice.
AB  - Intercultural living-a living that dwells "in-between" spaces of cultures-how it
      is conceptualized and what its lived experiences might mean, can give the
      direction for how we ought to care for one another. Drawing from my research with
      Vietnamese Canadian women, I argue that many immigrant women live and practice
      health care in "in-between" spaces, spaces that belong neither to East nor to
      West. Thus, supporting immigrant women's health care practices requires the
      removal of social ideologies that set apart the West and the "Other." To provide
      equal and quality health care, caring should occur within in-between spaces,
      spaces that belong to both those who provide and those who receive health care
      services.

PMID- 16893807
TI  - Swedish health care providers' experience and knowledge of female genital
      cutting.
AB  - We sought to evaluate the experiences and knowledge of health care providers in
      Sweden regarding female genital cutting (FGC) as a health issue. Questionnaires
      (n = 2,707) were sent to providers in four major cities in Sweden and evaluated
      by means of descriptive statistics. Twenty-eight percent (n = 769/2,707)
      responded, of whom 60% had seen such patients. Seven providers, including 2
      pediatricians, were suspicious of patients with signs of recent genital cutting.
      Ten percent had been asked to perform reinfibulation after delivery. Thirty-eight
      providers had received inquiries about the possibility of performing FGC in
      Sweden.A majority of Swedish health care providers meet patients presenting with
      evidence of FGC performed long ago. However, very few of them have suspected
      recently cut patients. The results support the hypothesis that this practice is
      not as active among African immigrants in Sweden as in their countries of origin.
      If the prevalence was the same as in African countries, more pediatricians would
      be expected to meet current cut girls. National efforts and policy programs to
      prevent FGC in Sweden are recommended as effective, in accordance with current
      research and should especially be directed toward pediatricians.

PMID- 16893808
TI  - "You need to know where we're coming from": Canadian Aboriginal women's
      perspectives on culturally appropriate HIV counseling and testing.
AB  - The purpose of this qualitative descriptive study was to determine Canadian
      Aboriginal women's perspectives on culturally appropriate HIV counseling and
      testing. Data were collected through semistructured individual interviews with 7
      Aboriginal women, and one focus group, in a western Canadian city. Four major
      categories were elucidated through thematic content analysis: Aboriginal women's
      life experiences that may influence their risk of HIV infection and their
      response to testing; barriers to HIV testing; guiding principles of the ideal HIV
      testing situation; and characteristics of culturally appropriate HIV testing. The
      fear of being judged by both the Aboriginal and non-Aboriginal communities and
      the need for sensitivity to the historical and current context of Aboriginal
      women's life experiences were pervasive themes throughout the findings.

PMID- 16893809
TI  - Literature review: Afghanistan women's health crisis, health service delivery,
      and ethical issues for international aid.
AB  - The literature indicates that the health of women in Afghanistan is poor. In 1997
      maternal mortality in Afghanistan was one of the worst in the world. Difficulties
      in establishing health services revolve around fundamentalist Islamic ideas and
      ongoing violence within Afghanistan. The literature holds advice on key
      behaviours for health professionals who may chose to work in Afghanistan. The
      literature also identifies the local level action that is occurring as the issue
      of women's health is recognised. Humanitarian assistance has been provided, with
      international aid agencies having to weigh the ethical responsibilities they hold
      and one agency tragically facing the violent loss of its own staff. Easy answers
      are not in the literature, merely an opportunity to understand, consider, and
      take action about what is facing women in Afghanistan and those who try to help.

PMID- 16893810
TI  - Effects of Diaspirin Crosslinked Hemoglobin (DCLHb) on microcirculation and local
      tissue pO2 of striated skin muscle following resuscitation from hemorrhagic
      shock.
AB  - The hemoglobin based oxygen carrier (HBOC) Diaspirin Crosslinked Hemoglobin
      (DCLHb) has been developed to substitute not only the blood volume, but also to
      restore the oxygen-carrying properties of blood during hemorrhagic shock.
      However, it has been suggested that HBOCs may enhance the formation of free
      oxygen radicals through the release of free iron ions via the Haber-Weiss
      reaction. The aim of this study was to investigate the effects of DCLHb on the
      microcirculation, leukocyte-endothelial cell interaction and local tissue
      oxygenation in striated skin muscle of Syrian golden hamsters during and after
      resuscitation from hemorrhagic shock. In particular we focused on the local
      tissue oxygenation after resuscitation with DCLHb (hemoglobin content 10 g%)
      compared to resuscitation using autologous blood diluted to a hemoglobin content
      of 10 g%. Hemorrhagic shock was induced for 45 minutes by bleeding the animals at
      a rate of 33 ml/kg BW maintaining a mean arterial pressure of 30 +/- 5 mmHg.
      Animals were resuscitated either with 33 ml/kg BW 6% Dextran-60.000 or with 10 g%
      DCLHb. The control group received shed blood diluted with Ringers to a hemoglobin
      content of 10 g%. Intravital microscopy was used for investigation of the
      microcirculatory parameters and a multiwire platinum surface electrode for
      measurement of local tissue pO2 in striated skin muscle in the dorsal skinfold
      chamber of Syrian golden hamsters. Resuscitation from hemorrhagic shock with 10
      g% AUB revealed significant increase of leukocytes rolling in postcapillary
      venules at 30 to 120 minutes after resuscitation compared to baseline values.
      DCLHb turned out to reduce the number of firmly adherent leukocytes after
      resuscitation compared to 10 g% AUB. Microvascular permeability as an indicator
      for functional endothelial integrity revealed no significant differences between
      the groups. DCLHb and 10 g% AUB led to a significant increase in local tissue
      oxygenation after resuscitation from hemorrhagic shock. However, 10 g% AUB turned
      out to be most effective to restore the local tissue pO2 compared to Dx-60. Our
      findings indicate that DCLHb restores microvascular perfusion after critical
      hemorrhagic shock as efficient as Dx-60 and 10 g% AUB. The absence of enhanced
      leukocyte-endothelium interaction after resuscitation with DCLHb implies that
      this HBOC does not exacerbate formation of oxygen free radicals during
      reperfusion. DCLHb effectively increases local tissue pO2 after resuscitation
      from hemorrhagic shock; however, not as effectively as 10 g% AUB.

PMID- 16893811
TI  - Intravascular fluorocarbon-stabilized microbubbles protect against fatal anemia
      in rats.
AB  - It has earlier been hypothesized that intravascular microbubbles, derived from a
      dodecafluoropentane (DDFP) emulsion, can transport physiologically significant
      amounts of oxygen in the animal body. To test this notion, anesthetized oxygen
      breathing rats were rendered severely anemic by bleeding and volume replacement.
      Rats treated with 0.014 ml/kg of DDFP in a 2% emulsion had normal circulatory
      parameters and behaved normally when waking up from anesthesia while controls
      died during anesthesia. Oxygen-breathing intact rats given 0.01 ml/kg of DDFP had
      muscle oxygen tensions which, for about 2.5 hours, exceeded those of controls by
      50-100%. It was further verified in vitro that DDFP-derived microbubbles can
      exchange oxygen with a surrounding aqueous medium. Extrapolation from these
      experiments indicates that less than 1 ml of DDFP, in emulsion-form, could
      provide for the resting oxygen consumption of an adult person. This suggests
      various therapeutic uses of the emulsion.

PMID- 16893812
TI  - Immobilized iminobiotin on magnetic poly (vinyl alcohol) microspheres for single
      step purification of streptavidin.
AB  - Magnetic poly (vinyl alcohol) microspheres (MPVAMS) immobilized with iminobiotin
      as the ligand were prepared for the purification of streptavidin. Parameters of
      magnetic separation, including spacers, NHS-iminobiotin added, elution behavior,
      and sample treatment, were optimized to improve the purification efficiency to
      achieve the maximum recovery of the protein. Streptavidin was successfully
      purified 38-fold from culture supernatant in a single-step by iminobiotin-MPVAMS
      with an overall recovery of 90.15% and purity of 95.08%. Hence, this study
      effectively illustrated the favorable application of magnetic microcarriers for
      the purification of streptavidin.

PMID- 16893814
TI  - Bioenergy beads: a tool for regeneration of ATP/NTP in biocatalytic synthesis.
AB  - Active inclusion bodies of recombinant polyphosphate kinase were obtained by
      simple washing of Escherichia coli cells with nonionic detergent and then they
      were immobilized in agar/TiO2 beads. Bioenergy beads obtained are charged by
      polyphosphate to act as rechargeable supply of adenosine/nucleoside triphosphates
      (ATP/NTP), a practical tool for synthesis of artificial receptors.

PMID- 16893813
TI  - Synthesis and in vitro sorption properties of PAA-grafted cellulose beads for
      selective binding of LDL.
AB  - Poly(acrylic acid) (PAA)-grafted cellulose copolymer beads were synthesized and
      tested in vitro as an adsorbent for selective removal of low-density lipoprotein
      (LDL) from human plasma. The copolymers were prepared by graft copolymerization
      of acrylic acid (AA) onto porous cellulose beads using cerium ammonium nitrate
      (CAN) as an initiator. The effect of initiator concentration, monomer amount and
      reaction time on the grafting was examined, and it revealed that the extent of
      grafting could be controlled by setting the appropriate reaction conditions. In
      vitro batch-wise adsorption tests were conducted to evaluate the lipoprotein
      sorption properties of the resulted copolymer beads, and the effect of grafting
      conditions on the adsorption performance was investigated. It was shown that the
      binding capacities of the best adsorbent derived from the appropriate reaction
      conditions could reach 4.96 mg/g total cholesterol (TC) and 4.46 mg/g LDL
      cholesterol (LDL-C) from human plasma, respectively, without significantly
      affecting the contents of beneficial constitutes such as high-density lipoprotein
      (HDL) and total proteins (TP). The influences of plasma amount and adsorption
      period on the adsorption properties were also determined and analyzed. It appears
      that this kind of copolymer is worthy of being developed as an alternative LDL
      adsorbent.

PMID- 16893815
TI  - A new potentiometric ammonium electrode for biosensor construction.
AB  - New ammonium-selective membrane electrode based on poly(vinyl chloride) (PVC)
      membrane containing palmitic acid (a long-chain fatty acid) and nonactin as an
      ammonium ionophore for the determination of ammonium ions in the 10(-7) - 10(-1)
      mol/L concentration range was prepared and compared to those of the electrode
      prepared by using carboxylated PVC. Sebacate was used as a plasticiser for both
      of the ammonium sensor membranes. The analytical characteristics of the ammonium
      electrodes was investigated. The effect of pH, buffer concentration, temperature
      and stirring rate on the response to ammonium electrode was investigated. The
      linear working range and sensitivity of the electrodes were also determined.
      Ammonium electrodes give Nernstian response (52-58 mV/p[NH4+]) throughout the
      ammonium ion concentration range of 10(-1) to 10(-6)M with detection limits of
      10(-6)M ammonium ions. The ammonium-selective electrodes prepared by using the
      PVC membranes containing palmitic acid showed more effective performance than
      those of the carboxylated PVC. The ammonium ion sensor has potential application
      in the analysis of ammonium ions for biosensor construction.

PMID- 16893816
TI  - The relationship between childhood sexual abuse, complex post-traumatic stress
      disorder and alexithymia in two outpatient samples: examination of women treated
      in community and institutional clinics.
AB  - Relationships between trauma variables, complex post-traumatic stress disorder
      (complex PTSD), affect dysregulation, dissociation, somatization, and alexithymia
      were studied in 70 women with early-onset sexual abuse treated in community-based
      private (n = 25) or clinic outpatient settings (n = 45). Measures were the
      Toronto Alexithymia Scale-20 and the Psychological Trauma Assessment Program.
      Compared with the community sample, the clinic sample (1) met diagnostic criteria
      for both lifetime and current complex PTSD; (2) showed correlations between
      current affect dysregulation, dissociation, and somatization with alexithymia;
      and (3) higher levels of alexithymia. Results suggest the clinic sample continued
      to experience current forms of suffering, risk, and vulnerability associated with
      early-onset sexual trauma. The findings may have implications regarding types of
      treatment available in community versus clinic settings.

PMID- 16893817
TI  - History of child abuse and severity of adult depression: the mediating role of
      cognitive schema.
AB  - The link between childhood abuse, adult depression, and anxiety has been well
      studied, but few studies have empirically explored the mechanism of that link.
      Using a clinical sample of women, this study examined the relationship between
      retrospectively measured childhood abuse and neglect and current adult symptoms
      of anxiety and depression, via the mediating effects of cognitive style. This
      study found that women who reported a positive abuse history were significantly
      more depressed and exhibited more maladaptive schemas than women who did not
      report a history of abuse. Specifically, it would appear that cognitive styles
      marked by interpersonal disconnection and rejection are particularly pathogenic.
      These findings contribute to the growing literature by providing support for the
      role of cognitions in mediating the link between childhood abuse and
      psychopathology.

PMID- 16893818
TI  - Attributions and coping in sexually abused adolescents referred for group
      treatment.
AB  - This study aims to assess the predictive value of two sets of variables, self
      attributions, and coping behaviors, on sexually abused (SA) teenagers'
      functioning, while controlling for abuse-related and family variables. A total of
      103 female adolescents completed self-report measures to assess their
      psychological functioning in terms of anxiety, depression, PTSD, sexual concerns,
      dissociation, anger, their self-injurious behaviors, antisocial behaviors, and
      drug use. After controlling for SA and family characteristics, final regression
      models indicate that attributions and coping behaviors explained between 22% and
      39% of additional unique variance for seven out of the nine measures of
      adolescent functioning. Attributions and coping behaviors did not significantly
      explain additional variance for scores of antisocial behaviors and drug use.
      Personal attributions of blame for negative events were the strongest predictors
      of adolescents' functioning. Implications for future research and interventions
      are highlighted.

PMID- 16893819
TI  - Sexual abuse and sexual functioning in a chronic pelvic pain sample.
AB  - Sexual abuse, particularly childhood sexual abuse, has been linked to chronic
      pelvic pain and to sexual dysfunction, though the sexual functioning of survivors
      of sexual abuse has not been studied in a chronic pain population. Sixty-three
      women with chronic pelvic pain completed measures of sexual function, sexual
      abuse, and pain. Using an index of the extent of sexual abuse experiences in
      childhood and adolescence/adulthood, higher scores were related to lower rates of
      sexual activity, less satisfaction with orgasm and feelings of closeness with
      sexual partners, and greater severity of and interference from pain. Findings
      point to the importance of controlling for relationship status in analyses of
      long-term effects of sexual abuse and of assessing chronic pelvic pain patients
      for histories of sexual abuse using measures that address the extent or severity
      of abuse.

PMID- 16893820
TI  - Ethnic differences in symptom presentation of sexually abused girls.
AB  - Although researchers have begun to examine the issue of ethnic and cultural
      factors in childhood sexual abuse (CSA), relatively little has been done to look
      at possible ethnic and cultural differences in psychological symptoms related to
      CSA. This study investigated the relationship between ethnicity and symptom
      presentation among Hispanic, African American, and Caucasian sexually abused
      girls. The study examined the relationship between ethnicity and depression,
      ethnicity and post-trauma intrusive symptoms, and ethnicity and post-trauma
      avoidance symptoms. Results indicated that African American girls had
      significantly higher levels of post-trauma avoidance symptoms than Hispanic
      girls, but not Caucasian girls. No significant differences were found between
      ethnic groups for depression or intrusive symptoms.

PMID- 16893821
TI  - The effects of interviewer race and child race on sexual abuse disclosures in
      forensic interviews.
AB  - This study examined the impact of interviewer race and child race on disclosures
      by alleged child sexual abuse victims during forensic interviews. Despite
      findings that supportiveness of caretaker, gender of interviewer, gender of
      child, and age of child affect disclosure, previous studies have failed to
      examine race as a variable impacting disclosure in a real-world setting. The
      study examined 220 cases from an archive of reports generated from forensic
      interviews in an urban setting. The reports were reviewed and coded for degree of
      disclosure, focusing on African American and Caucasian children and interviewers.
      The results indicate that child race and the interaction of child race and
      interviewer race reliably distinguished between no disclosure, tentative
      disclosure, and disclosure with detailed account of activity, while interviewer
      race alone failed to serve as a significant predictor. The interaction between
      child race and interviewer race was not in the predicted direction, with cross
      race dyads disclosing more than same-race dyads. Results are discussed in the
      context of real-world applications versus the previous analogue child sexual
      abuse literature.

PMID- 16893823
TI  - Current issues in lesbian, gay, bisexual, and transgender (LGBT) health:
      introduction.

PMID- 16893824
TI  - Disclosure of sexual orientation and behavior in the Nurses' Health Study II:
      results from a pilot study.
AB  - OBJECTIVE: To examine disclosure of sexual orientation and response rates in a
      pilot study of questions on sexual orientation and gender of sexual partners in
      the Nurses' Health Study II. METHODS: A pilot questionnaire was mailed to random
      samples of 350 women from each of three marital status strata: never married,
      previously married, and currently married. We estimated prevalence of each
      category of sexual orientation in the pilot study. Response rates to the sexual
      orientation question for the pilot questionnaire and the 1995 cohort
      questionnaire were compared. RESULTS: The overall response rate to the pilot
      study was 78%. In the pilot study, 98% of women reported a sexual orientation of
      heterosexual, 0.1% bisexual, and 0.9% lesbian, with 0.7% either declining to
      answer, leaving the question blank, or categorizing themselves as none of the
      above, weighted for stratified sampling by marital status. The distribution of
      sexual orientation in the cohort study (N = 91,654) was similar. Asking women to
      participate in the pilot study of sexual orientation questions did not appear to
      cause participants to drop out of the cohort. Concordance between reported sexual
      orientation on the pilot study and the cohort study was high. CONCLUSIONS: Based
      on our experience, researchers may be encouraged to add questions on sexual
      orientation to large studies of women.

PMID- 16893825
TI  - Mental health issues: a comparison of lesbian, bisexual and heterosexual women.
AB  - This study examines mental health issues among women of different sexual
      orientations. An anonymous survey was administered at 33 health care sites across
      the United States; the sample (N = 1304) included lesbians (n = 524), bisexual (n
      = 143) and heterosexual women (n = 637). Not only did sexual orientation
      influence the probability of experiencing emotional stress, but also whether a
      bisexual woman or lesbian had disclosed her sexual orientation (was "out")
      impacted the likelihood of having or having had mental health problems. Bisexual
      women and lesbians experienced more emotional stress as teenagers than did
      heterosexual women. Bisexual women were more than twice as likely to have had an
      eating disorder compared to lesbians. If a bisexual woman reported being out she
      was twice as likely to have had an eating disorder compared to a heterosexual
      woman. Lesbians who were not out and bisexual women who were out were 2-2.5 times
      more likely to experience suicidal ideation in the past 12 months. Lesbians and
      bisexual women who were not out were more likely to have had a suicide attempt
      compared to heterosexual women. Lesbians used psychotherapy for depression more
      commonly than did heterosexual or bisexual women. This is one of the few studies
      that compares lesbians, bisexual and heterosexual women. The implications of
      these findings are discussed.

PMID- 16893826
TI  - Factors associated with 'feeling suicidal': the role of sexual identity.
AB  - This paper examines factors associated with feeling suicidal in a large sample of
      urban men in Sydney and Melbourne, aged 18-50, including heterosexual, gay and
      bisexual men, HIV antibody positive and HIV antibody negative. As in previous
      research, sexuality (being homosexual or bisexual) was found to be a major
      predictor of suicidality. The research went some way towards explaining the close
      relationship between feeling suicidal and sexual orientation. Sexuality interacts
      with feeling bad in that, once men feel moderately bad/depressed, they are more
      likely to feel suicidal if they are homosexual or bisexual than if they are
      heterosexual. In addition, the research found that experience of verbal abuse and
      physical assault (harassment) increased feeling suicidal for both heterosexual
      and gay/bisexual men, not just for homosexual men as suggested by previous
      research, and that social isolation in the form of living alone is a further risk
      factor. Seeking counseling help and taking sexual risks were also independently
      associated with feeling suicidal. These actions may result from feeling suicidal
      rather than the reverse, and their association with feeling suicidal warrants
      further research. Many of the 46 independent variables examined in the research,
      including HIV antibody status and closeness to the HIV/ AIDS epidemic, were
      related to feeling suicidal only through their association with being
      gay/bisexual. Celibacy and general risk taking were not related to feeling
      suicidal in this study.

PMID- 16893827
TI  - Sexual identity distress, social support, and the health of gay, lesbian, and
      bisexual youth.
AB  - Sex researchers and mental health clinicians have long recognized that the stigma
      surrounding homosexuality plays an important role in shaping the social
      psychological adjustment of gay, lesbian, and bisexual (g/l/b) people. In recent
      years, researchers have suggested that sexual identity- related distress may
      influence the physical health status of g/l/b people, primarily because of the
      ways these self-related feelings and beliefs impact patterns of health-related
      behavior. This study examines the influence of sexual identity distress and
      social support on g/l/b youth's drug and alcohol use, psychological distress, and
      risky sexual behavior. The data come from a services research demonstration
      program conducted at the Indiana Youth Group, Inc., a g/l/b youth development
      agency based in Indianapolis, Indiana. Results indicate that sexual identity
      distress is strongly associated with psychological distress, less frequent use of
      alcohol, and using fewer types of illegal drugs. Being out to more people in
      one's support network, however, attenuates the severity of youth's sexual
      identity-related distress. Youth who report more support ties to g/l/b people
      indicate engaging in more frequent risky sexual behavior. The implications of
      these findings for theories of g/l/b youth's sexual identity development are
      discussed.

PMID- 16893828
TI  - Transgender youth: invisible and vulnerable.
AB  - This study used three focus groups to explore factors that affect the experiences
      of youth (ages 15 to 21) who identify as transgender. The focus groups were
      designed to probe transgender youths' experiences of vulnerability in the areas
      of health and mental health. This involved their exposure to risks,
      discrimination, marginalization, and their access to supportive resources. Three
      themes emerged from an analysis of the groups' conversations. The themes centered
      on gender identity and gender presentation, sexuality and sexual orientation, and
      vulnerability and health issues. Most youth reported feeling they were
      transgender at puberty, and they experienced negative reactions to their gender
      atypical behaviors, as well as confusion between their gender identity and sexual
      orientation. Youth noted four problems related to their vulnerability in health
      related areas: the lack of safe environments, poor access to physical health
      services, inadequate resources to address their mental health concerns, and a
      lack of continuity of caregiving by their families and communities.

PMID- 16893829
TI  - Slivers of the journey: the use of photovoice and storytelling to examine female
      to male transsexuals' experience of health care access.
AB  - The purpose of this research project was to examine female to male transsexuals'
      (FTMs) experiences of accessing health care. This was accomplished by documenting
      and recording the experiences of five FTMs through the use of photography and
      interviews. It was hoped that such an inquiry would provide a starting point for
      future research about the health care needs of the transgender community, and
      document some of the health care needs of the FTM community that would lead to
      recommendations for policy changes and educating providers.

PMID- 16893830
TI  - Understanding the experiences of lesbian, bisexual and trans survivors of
      domestic violence: a qualitative study.
AB  - OBJECTIVES: Using a participatory approach, our objectives were to understand
      community perspectives on domestic violence (DV) in lesbian, bisexual and trans
      (LBT) communities, and to assess access to and cultural appropriateness
      ofDVservices for LBT survivors. METHODS: We used qualitative methods and
      conducted focus groups and semi-structured interviews with LBT survivors of DV.
      RESULTS: Nearly all participants reported that the level of awareness regarding
      DV in their communities was limited. Survivors reported difficulty identifying
      their partners' behavior as abusive. Isolation was described as central to
      experiences of abuse, and respondents discussed a variety of isolation tactics
      specific to LBT communities. Isolation also contributed to difficulty seeking
      help. Respondents reported that they often did not access mainstream DV services
      due to concerns about homophobia and transphobia. To address DV in LBT
      communities respondents pointed to the importance of friendship and community
      networks, sharing information about queer DV, and holding batterers accountable
      for their behavior. CONCLUSIONS: LBT people face challenges identifying and
      responding to DV that are specific to their cultural context. Services for LBT DV
      survivors must be culturally appropriate and accessible. Community based
      solutions for addressing and preventing DV should be encouraged.

PMID- 16893831
TI  - Need for HIV/AIDS education and intervention for MTF transgenders: responding to
      the challenge.
AB  - The purpose of this paper is to report on the use of qualitative and quantitative
      research to develop an HIV/AIDS education intervention for MTF transgenders.
      Findings revealed that MTF transgenders have high prevalence of adverse health
      outcomes such as HIV, substance use, and psychological problems. MTF transgenders
      of color-African American, Latina, and Asian Pacific Islanders-experience
      heightened risk due to multiple stigmas associated with ethnicity and gender
      identity. Based on this evidence of need, we developed a series of transgender-
      specific HIV prevention, substance use and mental health treatment, and health
      education programs. Future health programs for stigmatized gender minorities,
      such as MTF transgenders, will benefit from conducting descriptive studies to
      identify the health needs of the community, and by linking research scientists,
      health providers, and community agencies to form a collaborative network for
      delivering evidence based and community sensitive services.

PMID- 16893832
TI  - Several perspectives provide insight into Hispanic farm workers' issues.

PMID- 16893833
TI  - Recent animal disease outbreaks and their impact on human populations.
AB  - Over the past 20 years, headlines have documented an increasing number of
      emerging diseases; most have an animal source (zoonoses). Recent examples include
      West Nile virus, severe acute respiratory syndrome (SARS), avian influenza, and
      monkeypox. While some emerging diseases occur among both humans and animals,
      others affect only animals or only humans. Nevertheless, all these new or
      reemerging infections have societal implications, often tied to local and
      national economies. It is important to understand the implications of emerging
      animal diseases and encourage stronger collaboration of veterinary and medical
      practitioners, especially in rural areas. Illnesses in agricultural workers may
      be the index cases for newly emerging diseases.

PMID- 16893835
TI  - Educational needs assessment for pediatric health care providers on pesticide
      toxicity.
AB  - PURPOSE: This pilot project, carried out under the National Strategies for Health
      Care Providers: Pesticides Initiative, assessed the attitudes, beliefs and
      practices of pediatricians, nurse practitioners, physicians assistants, and
      nurses in the metropolitan Washington, D.C., area and the surrounding rural
      counties regarding health effects of pesticide toxicity and continuing education
      on pesticide toxicity in the years 2001-2002. METHODS: Data were collected from
      practitioners (physicians, physician assistants, and nurse practitioners) and
      nurses using questionnaires as well as from practitioners using focus groups.
      Sites for questionnaire distribution and focus groups were selected to represent
      a variety of practice types and geographic settings. One-hundred-sixty
      questionnaires from practitioners and 43 from nurses were analyzed. These issues
      were probed further in six focus groups with 29 participants. RESULTS: Most
      respondents in both groups did not frequently diagnose or ask questions about
      pesticide toxicity on patient histories. Most focus group participants were more
      comfortable answering questions about acute pesticide toxicity, and many relied
      on poison control centers for assistance with management of acute cases. They
      expressed less understanding and more uncertainties about chronic toxicity. When
      asked questions by patients, 64% of practitioners and 69% of nurses felt poorly
      prepared to answer them. Forty percent of practitioners but only 26% of nurses
      felt it was important to obtain more information on pesticides. There were
      divergent preferences on ways to obtain continuing medical education (CME) in
      general, but a recurrent theme was the need to make CME on pesticide toxicity
      clinically relevant and one topic among several in a CME conference. Lectures and
      short courses were the most commonly preferred modes of education among both
      practitioners and nurses. CONCLUSION: Educational materials to reach this
      population of pediatric clinicians on pesticides, as well as other environmental
      health topics, should make the case justifying the importance of the topics,
      highlight information of clinical relevance, and use a variety of media. These
      results should be confirmed before being generalized to a broader group of
      clinicians, although the consistency of findings between focus groups suggests
      they are robust, at least for this geographic area.

PMID- 16893834
TI  - Response accuracy of hazard identification in migrant farm workers.
AB  - This study assessed potential biases introduced by using maternal proxies for
      reporting work hazards, illness symptoms, and acute agricultural injuries in
      studies of migrant farmworker families. A convenience sample of 79 mother/spouse
      and mother/oldest child pairs was obtained from a two-year cohort study of
      migrant farmworker families from Starr County, Texas. Pairs completed an
      interviewer-administered survey including 27 close-ended items describing work
      history, illness symptoms, and acute injuries during the 2001 migration season.
      Data analysis included prevalence, sensitivity, and specificity measures.
      Maternal proxy reports of subjective symptoms of a spouse or child were
      approximately 50% lower than spouse or child self-reports. Sensitivity and
      specificity of mothers' responses regarding hazard items were higher for spouses
      than for children. For items measuring illness symptoms, sensitivity of mothers'
      responses for spouses and oldest child pairs was generally less than 30%;
      however, specificity was generally above 90%. For acute agricultural injury, the
      mother/spouse sensitivity was 75%, the mother/child 40%, and specificities were
      100% and 97%, respectively. Sensitivity and specificity for mother/ spouse pairs
      was generally higher than mother/child pairs for work hazards, illness symptoms
      and acute injuries. While mothers may be acceptable proxies for spouses in this
      population, efforts should be made to collect data directly from adolescent
      children in studies of agricultural injuries.

PMID- 16893837
TI  - Personal dust exposures at a food processing facility.
AB  - A field study was performed to quantify personal dust exposures at a food
      processing facility. A review of the literature shows very little exposure
      information in the food processing industry. The processing area consisted of a
      series of four rooms, connected by a closed-loop ventilation system, housed
      within a larger warehouse-type facility. Workers were exposed to various fruit
      and vegetable dusts during the grinding, sieving, mixing and packaging of freeze
      dried or air-dried products. Eight two-hour periods were monitored over two days.
      Personal total suspended particulate samples were collected on 37 mm PVC filters
      with 5 microm pore size according to National Institute for Occupational Safety
      and Health (NIOSH) Method 0500. The filters were analyzed gravimetrically. The
      two-hour task sampling personal dust exposures ranged from 0.33-103 mg/m3. For
      each worker, an eight-hour time weighted average (TWA) concentration was
      calculated, and these ranged from 3.08-59.8 mg/m3. Although there are no directly
      appropriate occupational exposure limits that may be used for comparison, we
      selected the Threshold Limit Value (TLV) for particulates not otherwise
      classified (PNOC) of 10 mg/m3 for inhalable particles. Neglecting the respiratory
      protection used, five out of eight of the worker time-weighted averages exceeded
      the TLV. It should be noted that the TLV is based on the inhalable fraction and
      in this study total suspended particulate was measured; additionally, the TLV is
      applicable for dusts that are insoluble or poorly soluble, and have low toxicity,
      which may have limited protective ability in this case due to the irritant nature
      of certain dusts (e.g., jalapeno peppers, aloe vera). Sieving resulted in
      significantly higher exposure than grinding and blending. Measuring area
      concentrations alone in this environment is not a sufficient method of estimating
      personal exposures due to work practices for some operations.

PMID- 16893836
TI  - Proportionate mortality among current and former members of the United Farm
      Workers of America, AFL-CIO, in California 1973-2000.
AB  - CONTEXT: To further investigate mortality among farm workers, a proportionate
      mortality ratio (PMR) analysis was conducted among the membership of the United
      Farm Workers of America (UFW), a farm worker labor union, for the years 1973-2000
      in the state of California. PURPOSE: This report compares proportionate mortality
      for 118 causes of death in the UFW and the general United States population,
      adjusting for age, sex, race and calendar year of death. In addition, an
      exploratory analysis was conducted comparing deaths in the UFW to deaths in the
      California Hispanic population. METHODS: A roster of members of the UFW was
      compared to the death certificate master files of the state of California for the
      years 1973 to 2000. Matches were detected using automated techniques and visual
      review. PMR and associated confidence intervals were calculated using the
      National Institute for Occupational Safety and Health Life Table Analysis System
      using deaths in the U.S. as the standard. A similar analysis was conducted
      limiting attention to the time period 1988-2000 and using deaths in the
      California Hispanic population as the standard. FINDINGS: There were a total of
      139,662 members of the union included in the linkage that yielded 3,977 deaths in
      the time period 1973-2000. Proportionate mortality in the farm workers was
      significantly elevated for respiratory tuberculosis, malignant neoplasms of the
      stomach, biliary passages, liver and gallbladder, and uterine cervix, diabetes
      mellitus, cerebrovascular disease, cirrhosis of the liver, and "other diseases of
      the digestive system." Transportation injuries including motor vehicles deaths,
      deaths from machine injuries, unintentional poisonings and assault and homicide
      were significantly elevated as well. Farm workers were at significantly lower
      risk of death from HIV-related disease, malignant neoplasms of the esophagus,
      intestine, pancreas, lung, urinary bladder, melanoma, and brain, all cancer
      deaths, "other diseases of the nervous system," ischemic heart disease,
      conductive disorder, "other diseases of the heart," emphysema, "other respiratory
      diseases," and symptoms and ill-defined conditions. These results were similar
      when using California Hispanic deaths as the standard for the years 1988-2000.
      There was still excess proportionate mortality from tuberculosis, cerebrovascular
      disease and unintentional injuries among the UFW members and lowered mortality
      from HIV related deaths, all cancer deaths combined and diseases of the heart.
      CONCLUSIONS: These results include some unique findings in regard to both excess
      and deficits of mortality that may be explained by the Hispanic ethnicity and
      recent immigration of the cohort.

PMID- 16893838
TI  - Stakeholder analysis of Florida farmworker housing.
AB  - Farmworkers, farmworker advocates, state and federal policy-makers, and
      researchers all consider adequate housing as central to successful migration,
      community building, and quality of life, including good health, among
      farmworkers. This study analyzes results from interviews and focus groups with
      stakeholders involved in Florida farmworker housing conducted with the goal of
      providing recommendations for future farmworker housing policy. These
      recommendations include considering housing needs within a life continuum and
      understanding how wages and housing are interconnected. The concurring
      perspectives of stakeholders can be considered as building blocks in developing
      more effective state and local housing policy.

PMID- 16893839
TI  - An agromedicine initiative for first-year medical students, 1998-2004:
      biochemistry seminar proves feasible.
AB  - This report describes a 20 class-hour, 10-session seminar on agromedicine
      oriented topics, delivered as part of a basic science course for medical students
      (biochemistry) at the Medical University of South Carolina. The course was
      initiated in 1998 and continued through 2004. The preceptors are family medicine
      and agricultural research professors. Concepts from primary care, epidemiology,
      entomology, toxicology, and food science appeal strongly to the first-year
      medical student group (limited to 10 students). The agromedicine/environmental
      medicine seminar series is one of 16 research seminars available for in-depth
      study. As part of the course in biochemistry, this seminar has earned positive
      evaluations from medical students who expect to widen their perspective on global
      health and the environment. Seminar topics include food safety, farm trauma,
      nutraceuticals, crop protection, insect-borne disease, occupational health and
      safety, diet and cancer, birth defects, and bioengineering. Seventy medical
      students have participated in the interdisciplinary seminar. They perceive
      environmental science as affecting the health of their patients and as an
      essential part of their preparation for curative and preventive medicine. Readers
      may find medical school curriculum committees more receptive to accepting and
      continuing an agromedicine offering if it can be incorporated in a basic science
      course such as biochemistry or pharmacology.

PMID- 16893843
TI  - Health sciences librarians' reference services during a disaster: more than
      collection protection.
AB  - Reliable and timely professional information services are always important, but
      even more so during a community-wide disaster, like the aftermath of Hurricane
      Katrina. There are classes and literature on planning for library collection
      protection in local emergencies, but little about planning for reference and
      information services. Four accounts from South Louisiana in September of 2005
      demonstrate the value of proactive and innovative services based on professional
      information needs analysis skills. More study of such cases could lead to the
      development of best practice guidelines for the planning and provision of
      disaster information services.

PMID- 16893844
TI  - TOXMAP: a GIS-based gateway to environmental health resources.
AB  - The National Library of Medicine (NLM) has an extensive collection of
      environmental health information, including bibliographic and technical data on
      hazardous chemical substances, in its TOXNET <http://toxnet.nlm.nih.gov>
      databases. TOXNET also provides access to the United States Environment
      Protection Agency (EPA)'s Toxics Release Inventory (TRI) data, which covers
      release of specific chemicals via air, water, and land, and by underground
      injection, as reported by industrial facilities around the United States. NLM has
      developed a Web-based geographic information system (GIS), TOXMAP
      <http://toxmap.nlm. nih.gov/>, which allows users to create dynamic maps that
      show where TRI chemicals are released and that provides direct links to
      information about the chemicals in TOXNET. By extracting the associated regional
      geographic text terms from the displayed map (e.g., rivers, towns, county,
      state), TOXMAP also provides customized chemical and/or region-specific searches
      of NLM's bibliographic biomedical resources. This paper focuses on TOXMAP's
      features, data accuracy issues, challenges, user feedback techniques, and future
      directions.

PMID- 16893845
TI  - Not just for celebrities: collaborating with a PR representative to market
      library education services.
AB  - Hardin Library for the Health Sciences offers an education service called Hardin
      House Calls. In collaboration with the University of Iowa libraries' public
      relations coordinator, the education team developed a marketing campaign for
      Hardin House Calls. Marketing strategies included designing a new logo, meeting
      with external relations representatives and faculty, distributing a user survey,
      and producing and distributing posters and advertisements. These marketing
      strategies greatly increased the visibility and use of Hardin House Calls. The
      campaign also led to a series of faculty development sessions, education
      collaborations with smaller health sciences departments, and collection
      development opportunities. Promoting an instructional service through a public
      relations frameworkwas found to be a highly successful strategy.

PMID- 16893846
TI  - Retention of EBM competencies.
AB  - This longitudinal follow-up study surveyed the attitudes toward, and skills in,
      evidence-based medicine (EBM) of medical school graduates who had participated in
      a formal EBM curriculum during their third-year Internal Medicine (IM) clerkship.
      The objective was to measure whether competencies were retained over time and to
      identify the long- term impact on the graduates' attitudes toward, and
      proficiency in, EBM after graduation. Questionnaire results showed that a group
      of medical school graduates retained EBM skills and a positive attitude about the
      importance of applying EBM principles in patient care one to three years after
      completing an EBM course.

PMID- 16893847
TI  - HaPI-the health and psychosocial instruments database available from Ovid.
AB  - HaPI is the database of choice for locating information on all manner of
      measurement instruments, including questionnaires, interview schedules, rating
      scales, and much more. The database is easy to use, and offers unique fields to
      search, and a few choice limits.

PMID- 16893848
TI  - Native American health: traditional healing and culturally competent health care
      internet resources.
AB  - Health disparities between Native Americans and the general population of the
      United States are a major health concern. Traditional healing and culturally
      competent health care offer much promise in raising the health status of Native
      Americans. Traditional healing, although uniquely practiced by each indigenous
      culture, is generally a system of medicine based on the inseparability of mind,
      body, and spirit. Culturally competent health care, care that is congruent with
      the culture and language of the patient, is a growing initiative in western
      medicine. This article outlines Internet sites and online resources relevant to
      the study and practice of traditional healing and culturally competent health
      care.

PMID- 16893849
TI  - Implementing a personalized resource management program for a small medical
      library by using LinkOut.
AB  - End users want easy access to electronic full-text articles from their desktops.
      This small medical library has implemented an easy and cost-effective resource
      management program to meet this user need. This column will describe the
      implementation, use, and maintenance of the National Library of Medicine's
      LinkOut, a personalized resource management program that provides immediate
      access to the library's online journal full-text holdings via hyperlinks.

PMID- 16893850
TI  - Multimedia bootcamp: encouraging faculty to integrate technology in teaching.
AB  - As students entering college, graduate, and professional schools have increased
      needs and preferences for multimedia in instruction, faculty need to learn
      appropriate techniques for integrating technology into their educational duties.
      Instructional designers at the Claude Moore Health Sciences Library at the
      University of Virginia developed and implemented aMultimedia Bootcamp to help
      faculty and their support staff develop the skills necessary to integrate
      technology into teaching.

PMID- 16893854
TI  - Insulin therapy in pediatric patients with type I diabetes: continuous
      subcutaneous insulin infusion versus multiple daily injections.
AB  - The goal of this article was to review studies comparing continuous subcutaneous
      insulin infusion (CSII) to multiple daily insulin injections (MDIs) in children
      and adolescents with type I diabetes on five parameters: glycemic control,
      adverse events, required insulin dosage, weight gain, and psychosocial
      implications. Two of the five studies (sample sizes 19-75 patients) showed that
      insulin pumps provided better glycemic control, fewer adverse events, and better
      psychosocial implications than MDIs. Three of the five showed a lower required
      insulin dosage in CSII and one of the five showed less weight gain with CSII.
      Studies 4 and 5, both done in preschoolers, showed no significant difference on
      any of the five parameters. The majority of the patients and families chose to
      continue with CSII after the completion of the studies, even in studies where
      insulin pumps showed no objective benefit. Insulin pumps appear to offer
      potential benefit over MDIs, but the efficacy, safety, and cost effectiveness of
      CSII versus MDIs as first-line therapy for type I diabetes in this population has
      not yet been clearly established. Until more data are available from large,
      randomized, controlled studies, MDIs may be used as first-line therapy and CSII
      should be considered in patients who have poor glycemic control or who are not
      compliant with multiple injections.

PMID- 16893853
TI  - Pathogen shifts and changing cure rates for otitis media and tonsillopharyngitis.
AB  - Pneumococcal conjugate vaccine use has caused a decrease in the incidence of
      recurrent and refractory acute otitis media in the United States and a shift in
      the predominant pathogens. Now Haemophilus influenzae is the most commonly
      isolated organism (about 60% of the total), and more than half the strains make
      beta-lactamase, rendering them resistant to amoxicillin. Penicillin
      nonsusceptible pneumococci, the main target of antibiotic therapy in the 1990s,
      has become a much less common isolate (10%- 25% of the total). These changes
      impact antibiotic selection for acute otitis media. Penicillin treatment of group
      A streptococcal tonsillopharyngitis does not meet the minimum United States Food
      and Drug Administration standards for first-line treatment, which is 85% or
      greater eradication at the end of therapy. Recent results with amoxicillin
      suggest its efficacy is also waning. Cephalosporins have the highest
      bacteriologic and clinical efficacy. This has implications for optimal antibiotic
      therapy.

PMID- 16893855
TI  - Identifying patterns of developmental delays can help diagnose neurodevelopmental
      disorders.

PMID- 16893856
TI  - A safety-net antibiotic prescription for otitis media: the effects of a PBRN
      study on patients and practitioners.
AB  - Pediatricians can decrease antibiotic use by treating acute otitis media (AOM)
      with a safety-net antibiotic prescription (SNAP). This study assessed whether the
      practitioners of the Practice-Based Research Network who participated in the
      study continued to use the SNAP and report a 60-day follow-up of the study
      patients. Charts were reviewed of study patients for 60 days following study
      enrollment. A survey on antibiotic use for AOM was mailed to the 17 study
      practitioners (SP) and 30 randomly selected community pediatricians (CP). Eight
      of the SP used the SNAP more than 20 times over the year following the study vs 1
      of the CP. Sixty-two percent of patients never received antibiotics. The
      recurrence/relapse rate was greater in children younger than 2 years old compared
      to those older, 34% vs 10%. Practitioners who participate in a Practice-Based
      Research Network study are more likely to use a study intervention than others.

PMID- 16893857
TI  - Creatinine for evaluation of glomerular filtration rate in children.
AB  - This report is to provide primary care physicians with a convenient method for
      identifying children with impaired kidney function. This is important because of
      the prevalence of chronic kidney disease in adults and because intervention may
      delay disease progression. The glomerular filtration rate (GFR) measured using
      cimetidine clearance and calculated using height and serum creatinine
      concentration were compared during 222 clearance studies in 32 pediatric patients
      over 8 years. A child 1 year or older with a calculated GFR<60 mL/min/1.73 m2 has
      a significantly reduced GFR and should be referred to a pediatric nephrologist
      for further evaluation.

PMID- 16893858
TI  - C-reactive protein and leukocytes do not reliably indicate severity of influenza
      a infection in childhood.
AB  - Influenza in children may mimic other infections leading to insufficient
      treatment. Determination of parameters that facilitate diagnosis and indicate
      severity would be useful to optimize treatment modalities. We prospectively
      screened 432 children for influenza infection. Forty-six children at the age of 4
      weeks to 14 years (median, 18 months) with confirmed influenza A infection were
      analyzed. A clinical score of illness severity was calculated from the symptoms
      presented. To evaluate the dependency of the clinical score on C-reactive protein
      value, leukocyte count, age, and days of hospitalization, correlation and
      regression analyses were carried out. Neither the C-reactive protein values
      (median, 0.85 mg/dL; range, 0.2-18.6; r=0.14; p=0.35) nor the leukocyte counts
      (median, 7.95 G/L; range, 3.5-17.6; r=-0.14, p=0.34) correlated significantly
      with the clinical score of influenza severity. Thus, in daily clinical practice,
      C-reactive protein and leukocytes seem to be insufficient parameters to describe
      the clinical severity of influenza A infection in children.

PMID- 16893859
TI  - Co-location of mental health professionals in primary care settings: three North
      Carolina models.
AB  - The pressing need for identification and treatment of behavioral health disorders
      in primary care has renewed interest in the concept of co-located models of care.
      The purpose of this article is to describe three North Carolina practice models
      in which mental health professionals are co-located with pediatric primary care
      providers. Each of the models was sustainable, partly due to systemic changes
      brought about by advocacy efforts. In addition to providing practical guidance
      for possible replication in primary care, this article reflects on how advocacy
      efforts can impact the success of co-location models.

PMID- 16893860
TI  - Analysis of children with peripheral lymphadenopathy.
AB  - In this study, the clinical and laboratory features of children with
      lymphadenopathy were evaluated. Over a 3-year period, 126 patients were referred
      to the clinic for lymphadenopathy. Twenty-eight of cases have diseases mimicking
      lymphadenopathy; 98 (mean age: 86+/-55 months) have lymphadenopathy. Localized,
      limited, and generalized involvement was found in 52%, 30%, and 18% of patients.
      The most common localization was the head and neck region. The causes of
      lymphadenopathy were benign diseases in 75 patients. Sixty percent were reactive
      lymphadenopathy, 39% were lymphadenitis. Lymphadenitis was more frequently
      localized and bigger than 3 cm compared with reactive adenopathy (p=.02, p=.004).
      Twenty-three patients have malignant diseases whose mean age was higher than
      others (p=.002). The enlargement of supraclavicular nodes was more likely due to
      malignant disease (p=.001). The risk of malignant disease was higher in patients
      who had generalized lymphadenopathy, lymph nodes bigger than 3 cm,
      hepatosplenomegaly, and high lactate dehydrogenase levels. In conclusion, this
      study pointed out the important clues for the differential diagnosis, which were
      present in the history, physical, and laboratory findings.

PMID- 16893861
TI  - Plasma glucose concentrations in profound neonatal hypoglycemia.
AB  - The study goal was to define low thresholds of plasma glucose concentrations that
      constitute profound hypoglycemia. Population analysis was performed on research
      publications on neonatal hypoglycemia ascertained by a Medline search. Eligible
      patients had neurological sequelae associated directly and primarily with
      hypoglycemia (profound hypoglycemia). Of 89 infants, more than 95% had plasma
      glucose levels of less than 25 mg/dL that were first detected at more than 10
      hours of age. A breakdown of study patients according to those with or without
      neurological sequelae, who were exposed to a similar degree of hypoglycemia,
      showed a combined incidence of neurological injury of 21%, with 95% confidence
      interval from 14% to 27%.

PMID- 16893862
TI  - Hearing screening practices among a national sample of primary care
      pediatricians.
AB  - The objective of this study was to describe variations in hearing screening using
      a survey mailed to a national sample of primary care pediatricians prior to the
      2003 American Academy of Pediatrics (AAP) hearing screening guidelines. Of the
      390 primary care respondents, only 303 (78%) performed audiometry, routinely
      beginning at age 3 (32%), 4 (44%), or 5 (17%); 81% defined abnormal audiometry
      primarily as failure to hear at a specified decibel level: 15 dB hearing level
      (HL) (<1%), 16 to 20 dB HL (10%), 21 to 25 dB HL (23%), 26 to 30 dB HL (44%), 31
      to 40 dB HL (16%), and more than 40 dB HL (6%). This study serves as a baseline
      for comparison with postguideline practices.

PMID- 16893863
TI  - Dacryocystitis in children.

PMID- 16893864
TI  - Chiari I malformation: patient report and a mini review.

PMID- 16893865
TI  - Asymmetric mandibular dysplasia due to in utero compression.

PMID- 16893866
TI  - Stridor in an infant.

PMID- 16893867
TI  - Preauricular swelling.

PMID- 16893868
TI  - Summer reading.

PMID- 16893869
TI  - Culture and psychotherapy in a creolizing world.

PMID- 16893870
TI  - Cultural standards, power and subversion in cross-cultural psychotherapy.
AB  - In a creolizing world, psychotherapy is challenged by the growing influence of
      cultural standards, systems of meaning and idioms of distress supported by new
      groups who play a major role in public health policies. While these elements were
      originally introduced in psychotherapy with ethnic minorities both to improve the
      patient-doctor relationship and to bring relevant material from patients'
      cultural background, they also became a way to empower nonwestern patients in
      western health care systems. When in the 1980s it became possible to readdress
      the issue of power in psychiatric practice, something had already changed in the
      social regulation that psychiatry should endorse. In this article, the author
      focuses on the new legitimated social and cultural values that underpin the
      therapeutic process. While obviously these new values should be taken into
      account, the aim for psychotherapy remains to find a path for a 'subversive'
      practice that could be something more than just following social guidelines.

PMID- 16893871
TI  - Hidden points of view in cross-cultural psychotherapy and ethnography.
AB  - This article examines the challenges posed by cross-cultural psychotherapy in a
      creolized world, and the way this intersects with issues faced by the
      ethnographer. It proposes 'the relational subject,' implicit in systemic
      psychotherapy and social anthropology, as a framework for an understanding of
      communication. In cross-cultural psychotherapy, this assumption is central to non
      discriminatory and equitable treatment. Drawing on Bateson's ethnographic work,
      the article connects 'the relational subject' to what Bateson, following
      Whitehead, called 'the fallacy of misplaced concreteness' and later referred to
      as 'context.' The article examines the choices of 'context' first in ethnography
      and systemic psychotherapy and then in Bateson's own analysis of the Naven
      ritual. It is suggested that cross-cultural psychotherapy is psychotherapy in
      which the therapist keeps in mind, both her own and her client's contexts. This
      means an assessment of process (performative aspects) as well as content
      (semiotic aspects) and attention to 'moments' rather than longer sequences in the
      therapy.

PMID- 16893872
TI  - Group counseling and psychotherapy across the cultural divide: the case of
      Ethiopian Jewish immigrants in Israel.
AB  - Effective counseling across a cultural divide depends on adaptations or changes
      of technique to suit the particular intercultural circumstances. The concept of
      mutual creative space provides a guiding principle for therapists who wish to
      make such changes. This space is 'negotiated' between the therapist/counselor
      coming from the 'dominant/mainstream' group within society, and the group
      participants who arrive from another culture. Mutual creative space consists of
      the negotiation of power and a process of mutual invention, incorporating the
      creation, by therapist and participants, of something new that did not exist in
      either of their cultures of origin. A meaningful encounter and effective group
      counseling can take place following the negotiation of such a creative space.
      This is illustrated by the example of intercultural group work with Ethiopian
      Jewish immigrants in Israel, including an analysis of cultural characteristics of
      the Ethiopian group and specific ways of negotiating mutual creative space in
      this case. Issues discussed include: establishing trust in the cross cultural
      context; the use of body language and its interpretation; the psychologist as an
      authority figure; active participation vs. hidden learning; and working with
      dreams in such groups.

PMID- 16893873
TI  - Colonialism and countertransference: two cases of the sexual abuse of women by
      doctors.
AB  - The presentation of encounters with two migrant doctors with a past history of
      extreme sexual exploitation of their female patients presents an uncomfortable
      coming together of cultural observation, medical ethics and therapeutic
      transference. Colonial and postcolonial stereotypes evoked by their actions are
      briefly considered.

PMID- 16893874
TI  - Cross-cultural boundary dilemmas: a graded-risk assessment approach.
AB  - Behavioral health professionals are constantly faced with the dilemma of how to
      define boundaries in their relationships with clients. When working with groups
      from diverse cultures, defining boundaries becomes even more complex. This
      article urges a flexible approach, using the graded-risk model (Martinez, 2000)
      and a list of cultural factors for clinicians to consider. Possible benefits of
      reaching out to clients in concrete ways, as well as risks, are emphasized.
      Clients' notions of appropriate boundaries must be considered in the decision
      making process. Case examples from a refugee mental health clinic are used to
      elucidate a flexible approach to boundary decisions.

PMID- 16893875
TI  - Characteristics of Vietnamese patients attending an anxiety clinic in Australia
      and perceptions of the wider Vietnamese community about anxiety.
AB  - This article examined the causes underlying low utilization of mental health
      services by Vietnamese immigrants in Australia. Study 1 examined cases of
      Vietnamese patients who had attended an anxiety disorders clinic, while Study 2
      surveyed Vietnamese people in the community on their knowledge and attitudes
      towards common mental problems. Results from Study 1 showed that Vietnamese
      patients had significantly higher attrition rates, and presented with a larger
      number of nonanxiety disorders than their Australian-born counterparts. Study 2
      results indicated that many Vietnamese people did not differentiate clearly
      between the terms 'stress', 'anxiety' and 'depression'. Additionally, many
      participants felt that there was a generally negative cultural attitude towards
      people suffering from these problems and the mental health system itself. These
      outcomes suggest the importance of education for ethnic communities regarding
      available mental health facilities and treatments offered, as well as specific
      information on mental illness to help remove stigma.

PMID- 16893877
TI  - Lay concepts of depression among the Baganda of Uganda: a pilot study.
AB  - The literature indicates that although depression is highly prevalent, it is
      rarely recognized as such. The aim was to test the use of case vignettes in
      exploring the explanatory models of various subtypes of depression, in six
      individual interviews, and four focus-group discussions. Depressive symptoms
      presented in these vignettes seem to be conceptualized as a problem related to
      cognition (thinking too much) rather than emotion (sadness) and the resulting
      condition is referred to as 'illness of thoughts.' Worrisome thoughts resulting
      from various socioeconomic problems are seen as important aetiological factors
      for the illness of thoughts and require no medication as it is believed that
      there is no medication for thoughts. There are culturally accepted ways of
      dealing with and healing the condition. Once illness becomes recurrent or
      chronic, other explanations about causes and a different course of action have to
      be considered. Further exploration of the relationship between thoughts and
      emotions among the Baganda may be an important avenue for further research.

PMID- 16893876
TI  - Somatic and depressive symptoms in female Japanese and American students: a
      preliminary investigation.
AB  - The present study examined the relationship between common somatic symptoms and
      depression in samples of Japanese and American college students. Fifty Japanese
      and 44 American women completed the Beck Depression Inventory (BDI) and rated 56
      somatic-distress items for 7 days. Japanese had higher levels of somatic distress
      than Americans. ANOVA of somatic distress by BDI-level revealed that the High BDI
      Japanese group reported 26 somatic symptoms (including stomach ache, dizziness,
      and shoulder pain) with significantly higher means when compared with the low BDI
      group. High BDI Americans had a significantly higher mean for joint pain compared
      to the Low BDI group. The importance of the body in transcultural psychiatry is
      explored, and implications for primary and mental health care are discussed.

PMID- 16893879
TI  - Identification of PSME3 as a novel serum tumor marker for colorectal cancer by
      combining two-dimensional polyacrylamide gel electrophoresis with a strictly mass
      spectrometry-based approach for data analysis.
AB  - The purpose of this study was to identify and validate novel serological protein
      biomarkers of human colorectal cancer (CRC). Proteins from matched CRC and
      adjacent normal tissue samples were resolved by two-dimensional gel
      electrophoresis. From each gel all spots were excised, and enveloped proteins
      were identified by MS. By comparison of the resulting protein profiles,
      dysregulated proteins can be identified. A list of all identified proteins and
      validation of five exemplarily selected proteins, elevated in CRC was reported
      previously (Roessler, M., Rollinger, W., Palme, S., Hagmann, M. L., Berndt, P.,
      Engel, A. M., Schneidinger, B., Pfeffer, M., Andres, H., Karl, J., Bodenmuller,
      H., Ruschoff, J., Henkel, T., Rohr, G., Rossol, S., Rosch, W., Langen, H., Zolg,
      W., and Tacke, M. (2005) Identification of nicotinamide N-methyltransferase as a
      novel serum tumor marker for colorectal cancer. Clin. Cancer Res. 11, 6550-6557).
      Here we describe identification and initial validation of another potential
      marker protein for CRC. Comparison of tissue protein profiles revealed strong
      elevation of proteasome activator complex subunit 3 (PSME3) expression in CRC
      tissue. This dysregulation was not detectable based on the spot pattern. The
      PSME3-containing spot on tumor gels showed no visible difference to the
      corresponding spot on matched control gels. MS analysis revealed the presence of
      two proteins, PSME3 and annexin 4 (ANXA4) in one and the same spot on tumor gels,
      whereas the matched spot contained only one protein, ANXA4, on control gels.
      Therefore, dysregulation of PSME3 was masked by ANXA4 and could only be
      recognized by MS-based analysis but not by image analysis. To validate this
      finding, antibody to PSME3 was developed, and up-regulation in CRC was confirmed
      by Western blot analysis and immunohistochemistry. Finally by developing a highly
      sensitive immunoassay, PSME3 could be detected in human sera and was
      significantly elevated in CRC patients compared with healthy donors and patients
      with benign bowel disease. We propose that PSME3 be considered a novel serum
      tumor marker for CRC that may have significance in the detection and in the
      management of patients with this disease. Further studies are needed to fully
      assess the potential clinical value of this marker candidate.

PMID- 16893880
TI  - Substrate recognition and catalysis by the exoribonuclease RNase R.
AB  - RNase R is a processive, 3' to 5' hydrolytic exoribonuclease that together with
      polynucleotide phosphorylase plays an important role in the degradation of
      structured RNAs. However, RNase R differs from other exoribonucleases in that it
      can by itself degrade RNAs with extensive secondary structure provided that a
      single-stranded 3' overhang is present. Using a variety of specifically designed
      substrates, we show here that a 3' overhang of at least 7 nucleotides is required
      for tight binding and activity, whereas optimum binding and activity are achieved
      when the overhang is 10 or more nucleotides in length. In contrast, duplex RNAs
      with no overhang or with a 4-nucleotide overhang bind extremely poorly to RNase R
      and are inactive as substrates. A duplex RNA with a 10-nucleotide 5' overhang
      also is not a substrate. Interestingly, this molecule is bound only weakly,
      indicating that RNase R does not simply recognize single-stranded RNA, but the
      RNA must thread into the enzyme with 3' to 5' polarity. We also show that ribose
      moieties are required for recognition of the substrate as a whole since RNase R
      is unable to bind or degrade single-stranded DNA. However, RNA molecules with
      deoxyribose or dideoxyribose residues at their 3' termini can be bound and
      degraded. Based on these data and a homology model of RNase R, derived from the
      structure of the closely related enzyme, RNase II, we present a model for how
      RNase R interacts with its substrates and degrades RNA.

PMID- 16893881
TI  - DNA binding properties of TAF1 isoforms with two AT-hooks.
AB  - TATA-binding protein-associated factor 1 (TAF1) is an essential component of the
      general transcription factor IID (TFIID), which nucleates assembly of the
      preinitiation complex for transcription by RNA polymerase II. TATA-binding
      protein and TAF1.TAF2 heterodimers are the only components of TFIID shown to bind
      specific DNA sequences (the TATA box and initiator, respectively), raising the
      question of how TFIID localizes to gene promoters that lack binding sites for
      these proteins. Here we demonstrate that Drosophila TAF1 protein isoforms TAF1-2
      and TAF1-4 directly bind DNA independently of TAF2. DNA binding by TAF1 isoforms
      is mediated by cooperative interactions of two identical AT-hook motifs, one of
      which is encoded by an alternatively spliced exon. Electrophoretic mobility shift
      assays revealed that TAF1-2 bound the minor groove of adenine-thymine-rich DNA
      with a preference for the sequence AAT. Alanine-scanning mutagenesis of the
      alternatively spliced AT-hook indicated that Lys and Arg residues made essential
      DNA contacts, whereas Gly and Pro residues within the Arg-Gly-Arg-Pro core
      sequence were less important for DNA binding, suggesting that AT-hooks are more
      divergent than previously predicted. TAF1-2 bound with variable affinity to the
      transcription start site of several Drosophila genes, and binding to the hsp70
      promoter was reduced by mutation of a single base pair at the transcription start
      site. Collectively, these data indicate that AT-hooks serve to anchor TAF1
      isoforms to the minor groove of adenine-thymine-rich Drosophila gene promoters
      and suggest a model in which regulated expression of TAF1 isoforms by alternative
      splicing contributes to gene-specific transcription.

PMID- 16893883
TI  - The polybasic region that follows the plant homeodomain zinc finger 1 of Pf1 is
      necessary and sufficient for specific phosphoinositide binding.
AB  - The plant homeodomain (PHD) zinc finger is one of 14 known zinc-binding domains.
      PHD domains have been found in more than 400 eukaryotic proteins and are
      characterized by a Cys(4)-His-Cys(3) zinc-binding motif that spans 50-80
      residues. The precise function of PHD domains is currently unknown; however, the
      PHD domains of the ING1 and ING2 tumor suppressors have been shown recently to
      bind phosphoinositides (PIs). We have recently identified a novel PHD-containing
      protein, Pf1, as a binding partner for the abundant and ubiquitous
      transcriptional corepressor mSin3A. Pf1 contains two PHD zinc fingers, PHD1 and
      PHD2, and functions to bridge mSin3A to the TLE1 corepressor. Here, we show that
      PHD1, but not PHD2, binds several monophosporylated PIs but most strongly to
      PI(3)P. Surprisingly, a polybasic region that follows the PHD1 is necessary for
      PI(3)P binding. Furthermore, this polybasic region binds specifically to PI(3)P
      when fused to maltose-binding protein, PHD2, or as an isolated peptide,
      demonstrating that it is sufficient for specific PI binding. By exchanging the
      polybasic regions between different PHD fingers we show that this region is a
      strong determinant of PI binding specificity. These findings establish the Pf1
      polybasic region as a phosphoinositide-binding module and suggest that the PHD
      domains function down-stream of phosphoinositide signaling triggered by the
      interaction between polybasic regions and phosphoinositides.

PMID- 16893882
TI  - Allelic gene regulation of Pcdh-alpha and Pcdh-gamma clusters involving both
      monoallelic and biallelic expression in single Purkinje cells.
AB  - The molecular basis for providing the identity and diversity of single neurons is
      a key for realizing the brain system. Diverse protocadherin isoforms encoded by
      the Pcdh-alpha and Pcdh-gamma gene clusters are expressed in all of the
      vertebrates studied. For the Pcdh-alpha isoforms, differential expression
      patterns have been found in single Purkinje cells by unusual monoallelic and
      combinatorial types of gene regulation. Here we investigated total allelic gene
      regulation in the Pcdh-alpha and -gamma clusters, including the C-type variable
      exons (C1 to C5) and the Pcdh-gammaA and -gammaB variable exons in single
      Purkinje cells. Using split single-cell reverse transcription-PCR analysis,
      almost all of the Purkinje cells at postnatal day 21 biallelically expressed all
      the C-type isoforms, whereas the Pcdh-alpha isoforms showed both monoallelic and
      combinatorial expression. The Pcdh-gammaA and -gammaB isoforms also showed
      differential regulation in each cell with both monoallelic and combinatorial gene
      regulation. These data indicated that different types of allelic gene regulation
      (monoallelic versus biallelic) occurred in the Pcdh-alpha and -gamma clusters,
      although they were spliced into the same constant exons. It has been reported
      that each C-type Pcdh-alpha or -gamma transcript has a different expression
      pattern during brain development, suggesting that the different C-type variable
      exons may code temporal diversity, although the Pcdh-alpha, -gammaA, and -gammaB
      isoforms were differential and combinatorial gene regulation within a single
      cell. Thus, the multiple gene regulations in the Pcdh-alpha and -gamma clusters
      had a potential mechanism for increasing the diversity of individual neurons in
      the brain.

PMID- 16893884
TI  - Mutational analysis of the conserved TGES loop of sarcoplasmic reticulum Ca2+
      ATPase.
AB  - Crystal structures have shown that the conserved TGES loop of the Ca2+-ATPase is
      isolated in the Ca2E1 state but becomes inserted in the catalytic site in E2
      states. Here, we have examined the kinetics of the partial reaction steps of the
      transport cycle and the binding of the phosphoryl analogs BeF, AlF, MgF, and
      vanadate in mutants with alterations to the TGES residues. The mutations
      encompassed variation of size, polarity, and charge of the side chains.
      Differential effects on the Ca2E1P --> E2P, E2P --> E2, and E2 --> Ca2E1
      reactions and the binding of the phosphoryl analogs were observed. In the E183D
      mutant, the E2P --> E2 dephosphorylation reaction proceeded at a rate as high as
      one-third that of the wild type, whereas it was very slow in the other Glu183
      mutants, including E183Q, thus demonstrating the need for a negatively charged
      carboxylate group to catalyze dephosphorylation. By contrast, the Ca2E1P --> E2P
      transition was accomplished at a reasonable rate with glutamine in place of
      Glu183, but not with aspartate, indicating that the length of the Glu183 side
      chain, in addition to its hydrogen bonding potential, is critical for Ca2E1P -->
      E2P. This transition was also slowed in mutants with alteration to other TGES
      residues. The data provide functional evidence in support of the proposed role of
      Glu183 in activating the water molecule involved in the E2P --> E2
      dephosphorylation and suggest a direct participation of the side chains of the
      TGES loop in the control and facilitation of the insertion of the loop in the
      catalytic site. The interactions of the TGES loop furthermore seem to facilitate
      its disengagement from the catalytic site during the E2 --> Ca2E1 transition.

PMID- 16893885
TI  - Crystal structure of unsaturated glucuronyl hydrolase complexed with substrate:
      molecular insights into its catalytic reaction mechanism.
AB  - Unsaturated glucuronyl hydrolase (UGL), which is a member of glycoside hydrolase
      family GH-88, is a bacterial enzyme that degrades mammalian glycosaminoglycans
      and bacterial biofilms. The enzyme, which acts on unsaturated oligosaccharides
      with an alpha-glycoside bond produced by microbial polysaccharide lyases
      responsible for bacterial invasion of host cells, was believed to release 4-deoxy
      l-threo-5-hexosulose-uronate (unsaturated glucuronic acid, or DeltaGlcA) and
      saccharide with a new nonreducing terminus by hydrolyzing the glycosidic bond. We
      detail the crystal structures of wild-type inactive mutant UGL of Bacillus sp.
      GL1 and its complex with a substrate (unsaturated chondroitin disaccharide),
      identify active site residues, and postulate a reaction mechanism catalyzed by
      UGL that triggers the hydration of the vinyl ether group in DeltaGlcA, based on
      the structural analysis of the enzyme-substrate complex and biochemical analysis.
      The proposed catalytic mechanism of UGL is a novel case among known glycosidases.
      Under the proposed mechanism, Asp-149 acts as a general acid and base catalyst to
      protonate the DeltaGlcA C4 atom and to deprotonate the water molecule. The
      deprotonated water molecule attacks the DeltaGlcA C5 atom to yield unstable
      hemiketal; this is followed by spontaneous conversion to an aldehyde (4-deoxy-l
      threo-5-hexosulose-uronate) and saccharide through hemiacetal formation and
      cleavage of the glycosidic bond. UGL is the first clarified alpha(6)/alpha(6)
      barrel enzyme using aspartic acid as the general acid/base catalyst.

PMID- 16893886
TI  - Reversible heart failure in G alpha(q) transgenic mice.
AB  - For many patients with cardiac insufficiency, the disease progresses inexorably
      to organ dilatation, pump failure, and death. Although there are examples of
      reversible heart failure in man, our understanding of how the myocardium repairs
      itself is limited. A well defined animal model of reversible heart failure would
      allow us to better investigate these restorative processes. Receptors that
      activate Galpha(q), a signal transduction molecule in the heterotrimeric G
      protein superfamily, are thought to play a key role in the development of heart
      failure. We demonstrated previously that mice expressing a recombinant Galpha(q)
      protein, the activity of which can be turned on or off at will in cardiac
      myocytes, develop a dilated cardiomyopathy with generalized edema and heart
      failure following activation of the protein (Fan, G., Jiang, Y.-P., Lu, Z.,
      Martin, D. W., Kelly, D. J., Zuckerman, J. M., Ballou, L. M., Cohen, I. S., and
      Lin, R. Z. (2005) J. Biol. Chem. 280, 40337-40346). Here we report that the
      contractile dysfunction and pathological structural changes in the myocardium
      improved significantly after termination of the Galpha(q) signal, even in animals
      with overt heart failure. Abnormalities in two proteins that regulate Ca(2+)
      handling in myocytes, phospholamban and the voltage-dependent L-type Ca(2+)
      channel, were also reversed, as was the increased expression of genes that are
      associated with heart failure. These results indicate that the heart has a
      substantial reparative capacity if the molecular signals responsible for the
      myocardial dysfunction can be identified and blocked.

PMID- 16893887
TI  - Ribosomal stress couples the unfolded protein response to p53-dependent cell
      cycle arrest.
AB  - Protein misfolding in the endoplasmic reticulum (ER) triggers a signaling pathway
      termed the unfolded protein response path-way (UPR). UPR signaling is transduced
      through the transmembrane ER effectors PKR-like ER kinase (PERK), inositol
      requiring kinase-1 (IRE-1), and activating transcription factor 6 (ATF6). PERK
      activation triggers phosphorylation of eIF2alpha leading to repression of protein
      synthesis, thereby relieving ER protein load and directly inhibiting cyclin D1
      translation thereby contributing to cell cycle arrest. However, PERK(-/-) murine
      embryonic fibroblasts have an attenuated G(1)/S arrest that is not attributable
      to cyclin D1 loss, suggesting a cyclin D1-independent mechanism. Here we show
      that the UPR triggers p53 accumulation and activation. UPR induction promotes
      enhanced interaction between the ribosome proteins (rpL5, rpL11, and rpL23) and
      Hdm2 in a PERK-dependent manner. Interaction with ribosomal proteins results in
      inhibition of Hdm2-mediated ubiquitination and degradation of p53. Our data
      demonstrate that ribosomal subunit:Hdm2 association couples the unfolded protein
      response to p53-dependent cell cycle arrest.

PMID- 16893888
TI  - Proteomic analysis of Salmonella enterica serovar typhimurium isolated from RAW
      264.7 macrophages: identification of a novel protein that contributes to the
      replication of serovar typhimurium inside macrophages.
AB  - To evade host resistance mechanisms, Salmonella enterica serovar Typhimurium
      (STM), a facultative intracellular pathogen, must alter its proteome following
      macrophage infection. To identify new colonization and virulence factors that
      mediate STM pathogenesis, we have isolated STM cells from RAW 264.7 macrophages
      at various time points following infection and used a liquid chromatography-mass
      spectrometry-based proteomic approach to detect the changes in STM protein
      abundance. Because host resistance to STM infection is strongly modulated by the
      expression of a functional host-resistant regulator, i.e. natural resistance
      associated macrophage protein 1 (Nramp1, also called Slc11a1), we have also
      examined the effects of Nramp1 activity on the changes of STM protein abundances.
      A total of 315 STM proteins have been identified from isolated STM cells, which
      are largely housekeeping proteins whose abundances remain relatively constant
      during the time course of infection. However, 39 STM proteins are strongly
      induced after infection, suggesting their involvement in modulating colonization
      and infection. Of the 39 induced proteins, 6 proteins are specifically modulated
      by Nramp1 activity, including STM3117, as well as STM3118-3119 whose time
      dependent abundance changes were confirmed using Western blot analysis. Deletion
      of the gene encoding STM3117 resulted in a dramatic reduction in the ability of
      STM to colonize wild-type RAW 264.7 macrophages, demonstrating a critical
      involvement of STM3117 in promoting the replication of STM inside macrophages.
      The predicted function common for STM3117-3119 is biosynthesis and modification
      of the peptidoglycan layer of the STM cell wall.

PMID- 16893889
TI  - Identification of novel glycogen synthase kinase-3beta substrate-interacting
      residues suggests a common mechanism for substrate recognition.
AB  - Substrate recognition and specificity are essential for the reliability and
      fidelity of protein kinase function. GSK-3 has a unique substrate specificity
      that requires prior phosphorylation of its substrates. However, how the enzyme
      selects its phosphorylated substrates is unknown. Here, we combined in silico
      modeling with mutagenesis and biological studies to identify GSK-3-substrate
      interaction sites located within its binding cleft. Protein-protein docking of
      GSK-3beta and the phosphorylated cAMP responsive element binding protein (pCREB)
      (using the available experimentally determined structures), identified Phe67,
      Gln89, and Asn95 of GSK-3beta as putative binding sites interacting with the CREB
      phosphorylation motif. Mutations of these residues to alanine impaired GSK-3beta
      phosphorylation of several substrates, without abrogating its autocatalytic
      activity. Subsequently, expression of the GSK-3beta mutants in cells resulted in
      decreased phosphorylation of substrates CREB, IRS-1, and beta-catenin, and
      prevented their suppression of glycogen synthase activity as compared with cells
      expressing the wild-type GSK-3beta. Our studies provide important additional
      understanding of how GSK-3beta recognizes its substrates: In addition to prior
      phosphorylation typically required in GSK-3 substrates, substrate recognition
      involves interactions with GSK-3beta residues: Phe67, Gln89, and Asn95, which
      confer a common basis for substrate binding and selectivity, yet allow for
      substrate diversity.

PMID- 16893890
TI  - Osmotic stress activates the TAK1-JNK pathway while blocking TAK1-mediated NF
      kappaB activation: TAO2 regulates TAK1 pathways.
AB  - Osmotic stress activates MAPKs, including JNK and p38, which play important roles
      in cellular stress responses. Transforming growth factor-beta-activated kinase 1
      (TAK1) is a member of the MAPK kinase kinase (MAPKKK) family and can activate JNK
      and p38. TAK1 can also activate IkappaB kinase (IKK) that leads to degradation of
      IkappaB and subsequent NF-kappaB activation. We found that TAK1 is essential for
      osmotic stress-induced activation of JNK but is not an exclusive mediator of p38
      activation. Furthermore, we found that although TAK1 was highly activated upon
      osmotic stress, it could not induce degradation of IkappaB or activation of NF
      kappaB. These results suggest that TAK1 activity is somehow modulated to function
      specifically in osmotic stress signaling, leading to the activation of JNK but
      not of IKK. To elucidate the mechanism underlying this modulation, we screened
      for potential TAK1-binding proteins. We found that TAO2 (thousand-and-one amino
      acid kinase 2) associates with TAK1 and can inhibit TAK1-mediated activation of
      NF-kappaB but not of JNK. We observed that TAO2 can interfere with the
      interaction between TAK1 and IKK and thus may regulate TAK1 function. TAK1 is
      activated by many distinct stimuli, including cytokines and stresses, and
      regulation by TAO2 may be important to activate specific intracellular signaling
      pathways that are unique to osmotic stress.

PMID- 16893891
TI  - Transcriptional regulation of the glucose-6-phosphatase gene by cAMP/vasoactive
      intestinal peptide in the intestine. Role of HNF4alpha, CREM, HNF1alpha, and
      C/EBPalpha.
AB  - Gluconeogenesis is induced in both the liver and intestine by increased cAMP
      levels. However, hepatic and intestinal glucose production can have opposite
      effects on glucose homeostasis. Glucose release into the portal vein by the
      intestine increases glucose uptake and reduces food intake. In contrast, glucose
      production by the liver contributes to hyperglycemia in type II diabetes. Glucose
      6-phosphatase (Glc6Pase) is the key enzyme of gluconeogenesis in both the liver
      and intestine. Here we specify the cAMP/protein kinase A regulation of the
      Glc6Pase gene in the intestine compared with the liver. Similarly to the liver,
      the molecular mechanism of cAMP/protein kinase A regulation involves cAMP
      response element-binding protein, HNF4alpha, CAAT/enhancer-binding protein, and
      HNF1. In contrast to the situation in the liver, we find that different isoforms
      of CAAT/enhancer-binding protein and HNF1 contribute to the specific regulation
      of the Glc6Pase gene in the intestine. Moreover, we show that cAMP-response
      element binding modulator specifically contributes to the regulation of the
      Glc6Pase gene in the intestine but not in the liver. These results allow us to
      identify intestine-specific regulators of the Glc6Pase gene and to improve the
      understanding of the differences in the regulation of gluconeogenesis in the
      intestine compared with the liver.

PMID- 16893893
TI  - BM88 is a dual function molecule inducing cell cycle exit and neuronal
      differentiation of neuroblastoma cells via cyclin D1 down-regulation and
      retinoblastoma protein hypophosphorylation.
AB  - Control of cell cycle progression/exit and differentiation of neuronal precursors
      is of paramount importance during brain development. BM88 is a neuronal protein
      associated with terminal neuron-generating divisions in vivo and is implicated in
      mechanisms underlying neuronal differentiation. Here we have used mouse
      neuroblastoma Neuro 2a cells as an in vitro model of neuronal differentiation to
      dissect the functional properties of BM88 by implementing gain- and loss-of
      function approaches. We demonstrate that stably transfected cells overexpressing
      BM88 acquire a neuronal phenotype in the absence of external stimuli, as judged
      by enhanced expression of neuronal markers and neurite outgrowth-inducing
      signaling molecules. In addition, cell cycle measurements involving cell growth
      assays, BrdUrd incorporation, and fluorescence-activated cell sorting analysis
      revealed that the BM88-transfected cells have a prolonged G(1) phase, most
      probably corresponding to cell cycle exit at the G(0) restriction point, as
      compared with controls. BM88 overexpression also results in increased levels of
      the cell cycle regulatory protein p53, and accumulation of the hypophosphorylated
      form of the retinoblastoma protein leading to cell cycle arrest, with concomitant
      decreased levels and, in many cells, cytoplasmic localization of cyclin D1.
      Conversely, BM88 gene silencing using RNA interference experiments resulted in
      acceleration of cell proliferation accompanied by impairment of retinoic acid
      induced neuronal differentiation of Neuro 2a cells. Taken together, our results
      suggest that BM88 plays an essential role in regulating cell cycle exit and
      differentiation of Neuro 2a cells toward a neuronal phenotype and further support
      its involvement in the proliferation/differentiation transition of neural
      stem/progenitor cells during embryonic development.

PMID- 16893892
TI  - Requirement of transmembrane transport for S-nitrosocysteine-dependent
      modification of intracellular thiols.
AB  - S-nitrosothiols have been implicated as intermediary transducers of nitric oxide
      bioactivity; however, the mechanisms by which these compounds affect cellular
      functions have not been fully established. In this study, we have examined the
      effect of S-nitrosothiol transport on intracellular thiol status and upon the
      activity of a target protein (caspase-3), in bovine aortic endothelial cells. We
      have previously demonstrated that the specific transport of amino acid-based S
      nitrosothiols (S-nitroso-L-cysteine and S-nitrosohomocysteine) occurs via amino
      acid transport system L to generate high levels of intracellular protein S
      nitrosothiols (Zhang, Y., and Hogg, N. (2004) Proc. Natl. Acad. Sci. U. S. A.
      101, 7891-7896). In this study, we demonstrate that the transport of S
      nitrosothiols is essential for these compounds to affect intracellular thiol
      levels and to modify intracellular protein activity. Importantly, the ability of
      these compounds to affect intracellular processes occurs independently of nitric
      oxide formation. These findings suggest that the major action of these compounds
      is not to liberate nitric oxide in the extracellular space but to be specifically
      transported into cells where they are able to modify cellular functions through
      nitric oxide-independent mechanisms.

PMID- 16893894
TI  - Structural and functional evidence for the role of the TLR2 DD loop in TLR1/TLR2
      heterodimerization and signaling.
AB  - The Toll/Interleukin-1 receptor (TIR) domain of the Toll-like receptors (TLRs)
      plays an important role in innate host defense signaling. The TIR-TIR platform
      formed by the dimerization of two TLRs promotes homotypic protein-protein
      interactions with additional cytoplasmic adapter molecules to form an active
      signaling complex resulting in the expression of pro- and anti-inflammatory
      cytokine genes. To generate a better understanding of the functional domains of
      TLR2 we performed a random mutagenesis analysis of the human TLR2 TIR domain and
      screened for TLR2/1 signaling-deficient mutants. Based upon the random
      mutagenesis results, we performed an alanine scanning mutagenesis of the TLR2 DD
      loop and part of the alphaD region. This resulted in the identification of four
      residues crucial for TLR2/1 signaling: Arg-748, Phe-749, Leu-752, and Arg-753.
      Computer-assisted energy minimization and docking studies indicated three regions
      of interaction in the TLR2/1 TIR-docked heterodimer. In Region I, residues Arg
      748 and Phe-749 in TLR2 DD loop were involved in close contacts with Gly-676 in
      the TLR1 BB loop. Because this model suggested that steric hindrance would
      significantly alter the binding interactions between DD loop of TLR2 and BB loop
      of TLR1, Gly-676 in TLR1 was rationally mutated to Ala and Leu. As expected, in
      vitro functional studies involving TLR1 G676A and TLR1 G676L resulted in reduced
      PAM(3)CSK(4) mediated NF-kappaB activation lending support to the computerized
      predictions. Additionally, mutation of an amino acid residue (TLR2 Asp-730) in
      Region II also resulted in decreased activity in agreement with our model,
      providing new insights into the structure-function relationship of TLR2/1 TIR
      domains.

PMID- 16893895
TI  - Human macrophage migration inhibitory factor: a proven immunomodulatory cytokine?
AB  - Macrophage migration inhibitory factor (MIF) is a pro-inflammatory mediator with
      the ability to induce various immunomodulatory responses and override
      glucocorticoid-driven immunosuppression. Some of these functions have been linked
      to the unusual enzymatic properties of the protein, namely tautomerase and
      oxidoreductase activities. However, there are conflicting reports regarding the
      functional role of these enzymatic properties in normal physiological homeostasis
      and disease progression. Therefore, we have produced a highly pure, virtually
      endotoxin-free recombinant MIF preparation and fully characterized this using a
      variety of biochemical and biophysical approaches. The recombinant protein, with
      demonstrable enzymatic activity, was then used to systematically examine the
      biological activity of MIF. Surprisingly, treatment with MIF alone failed to
      induce cytokine expression, with the exception of IL-8. However, co-treatment of
      lipopolysaccharide (LPS) in conjunction with MIF produced synergistic secretion
      of tumor necrosis factor-alpha, interleukin (IL)-1, and IL-8 compared with LPS
      alone. The potentiating effect of MIF was seen at physiologically relevant
      concentrations. These data suggest that MIF has no conventional cytokine activity
      but, rather, acts to modulate and amplify the response to LPS.

PMID- 16893896
TI  - Hereditary hemochromatosis protein, HFE, interaction with transferrin receptor 2
      suggests a molecular mechanism for mammalian iron sensing.
AB  - HFE and transferrin receptor 2 (TFR2) are membrane proteins integral to mammalian
      iron homeostasis and associated with human hereditary hemochromatosis. Here we
      demonstrate that HFE and TFR2 interact in cells, that this interaction is not
      abrogated by disease-associated mutations of HFE and TFR2, and that TFR2 competes
      with TFR1 for binding to HFE. We propose a new model for the mechanism of iron
      status sensing that results in the regulation of iron homeostasis.

PMID- 16893897
TI  - Molecular insights into nitrogenase FeMoco insertion: TRP-444 of MoFe protein
      alpha-subunit locks FeMoco in its binding site.
AB  - Biosynthesis of the FeMo cofactor (FeMoco) of nitrogenase MoFe protein is
      arguably one of the most complex processes in metalloprotein biochemistry. Here
      we investigate the role of a MoFe protein residue (Trp-alpha444) in the final
      step of FeMoco assembly, which involves the insertion of FeMoco into its binding
      site. Mutations of this aromatic residue to small uncharged ones result in
      significantly decreased levels of FeMoco insertion/retention and drastically
      reduced activities of MoFe proteins, suggesting that Trp-alpha444 may lock the
      FeMoco tightly in its binding site through the sterically restricting effect of
      its bulky, aromatic side chain. Additionally, these mutations cause partial
      conversion of the P-cluster to a more open conformation, indicating a potential
      connection between FeMoco insertion and P-cluster assembly. Our results provide
      some of the initial molecular insights into the FeMoco insertion process and,
      moreover, have useful implications for the overall scheme of nitrogenase
      assembly.

PMID- 16893898
TI  - Characterization of distant enhancers and promoters in the albumin-alpha
      fetoprotein locus during active and silenced expression.
AB  - The albumin and alpha-fetoprotein genes are adjacent and express closely related
      serum proteins. Both genes are strongly expressed in fetal liver, primarily
      through activation by distant enhancers, but the AFP gene selectively undergoes
      developmental silencing. We used chromatin immunoprecipitation to study enhancers
      and promoters during active and silenced gene expression. In adult phenotype
      cells, the silenced AFP gene was actively repressed at the promoter and two
      proximal enhancers, characterized by the absence of coactivators and acetylated
      histone 4, and the presence of corepressors and K9-methylated histone 3. Specific
      transcription factors, TBP, and RNA polymerase II were all detected on both
      active and silenced genes, indicating that both states were actively regulated.
      Surprisingly, promoter-specific factors were also detected on enhancers,
      especially with reduced chromatin shearing. Under these conditions, an enhancer
      specific factor was also detected on the albumin promoter. Association of
      promoter- and enhancer-specific factors was confirmed by sequential
      immunoprecipitation. Because no binding was detected on intervening segments,
      these promoter-enhancer associations suggest looping.

PMID- 16893899
TI  - N-(3-oxo-acyl)homoserine lactones signal cell activation through a mechanism
      distinct from the canonical pathogen-associated molecular pattern recognition
      receptor pathways.
AB  - Innate immune system receptors function as sensors of infection and trigger the
      immune responses through ligand-specific signaling pathways. These ligands are
      pathogen-associated products, such as components of bacterial walls and viral
      nuclear acids. A common response to such ligands is the activation of mitogen
      activated protein kinase p38, whereas double-stranded viral RNA additionally
      induces the phosphorylation of eukaryotic translation initiation factor 2alpha
      (eIF2alpha). Here we have shown that p38 and eIF2alpha phosphorylation represent
      two biochemical markers of the effects induced by N-(3-oxo-acyl)homoserine
      lactones, the secreted products of a number of Gram-negative bacteria, including
      the human opportunistic pathogen Pseudomonas aeruginosa. Furthermore, N-(3-oxo
      dodecanoyl)homoserine lactone induced distension of mitochondria and the
      endoplasmic reticulum as well as c-jun gene transcription. These effects occurred
      in a wide variety of cell types including alveolar macrophages and bronchial
      epithelial cells, requiring the structural integrity of the lactone ring motif
      and its natural stereochemistry. These findings suggest that N-(3-oxo
      acyl)homoserine lactones might be recognized by receptors of the innate immune
      system. However, we provide evidence that N-(3-oxo-dodecanoyl)homoserine lactone
      mediated signaling does not require the presence of the canonical innate immune
      system receptors, Toll-like receptors, or two members of the NLR/Nod/Caterpillar
      family, Nod1 and Nod2. These data offer a new understanding of the effects of N
      (3-oxo-dodecanoyl)homoserine lactone on host cells and its role in persistent
      airway infections caused by P. aeruginosa.

PMID- 16893901
TI  - Glutaredoxin modulates platelet-derived growth factor-dependent cell signaling by
      regulating the redox status of low molecular weight protein-tyrosine phosphatase.
AB  - Glutaredoxin (GRX) is a glutathione-disulfide oxidoreductase involved in various
      cellular functions, including the redox-dependent regulation of certain integral
      proteins. Here we demonstrated that overexpression of GRX suppressed the
      proliferation of myocardiac H9c2 cells treated with platelet-derived growth
      factor (PDGF)-BB. After stimulation with PDGF-BB, the phosphorylation of PDGF
      receptor (PDGFR) beta was suppressed in GRX gene-transfected cells, compared with
      controls. Conversely, the phosphorylation was enhanced by depletion of GRX by RNA
      interference. In this study we focused on the role of low molecular weight
      protein-tyrosine phosphatase (LMW-PTP) in the dephosphorylation of PDGFRbeta via
      a redox-dependent mechanism. We found that depletion of LMW-PTP using RNA
      interference enhanced the PDGF-BB-induced phosphorylation of PDGFRbeta,
      indicating that LMW-PTP works for PDGFRbeta. The enhancement of the
      phosphorylation of PDGFRbeta was well correlated with inactivation of LMW-PTP by
      cellular peroxide generated in the cells stimulated with PDGF-BB. In vitro, with
      hydrogen peroxide treatment, LMW-PTP showed decreased activity with the
      concomitant formation of dithiothreitol-reducible oligomers. GRX protected LMW
      PTP from hydrogen peroxide-induced oxidation and inactivation in concert with
      glutathione, NADPH, and glutathione disulfide reductase. This strongly suggests
      that retention of activity of LMW-PTP by enhanced GRX expression suppresses the
      proliferation of cells treated with PDGF-BB via enhanced dephosphorylation of
      PDGFRbeta. Thus, GRX plays an important role in PDGF-BB-dependent cell
      proliferation by regulating the redox state of LMW-PTP.

PMID- 16893900
TI  - Caveolar endocytosis and microdomain association of a glycosphingolipid analog is
      dependent on its sphingosine stereochemistry.
AB  - We have previously shown that glycosphingolipid analogs are internalized
      primarily via caveolae in various cell types. This selective internalization was
      not dependent on particular carbohydrate headgroups or sphingosine chain length.
      Here, we examine the role of sphingosine structure in the endocytosis of
      BODIPYtrade mark-tagged lactosylceramide (LacCer) analogs via caveolae. We found
      that whereas the LacCer analog with the natural (D-erythro) sphingosine
      stereochemistry is internalized mainly via caveolae, the non-natural (L-threo)
      LacCer analog is taken up via clathrin-, RhoA-, and Cdc42-dependent mechanisms
      and largely excluded from uptake via caveolae. Unlike the D-erythro-LacCer
      analog, the L-threo analog did not cluster in membrane microdomains when added at
      higher concentrations (5-20 microm). In vitro studies using small unilamellar
      vesicles and giant unilamellar vesicles demonstrated that L-threo-LacCer did not
      undergo a concentration-dependent excimer shift in fluorescence emission such as
      that seen with BODIPYtrade mark-sphingolipids with natural stereochemistry.
      Molecular modeling studies suggest that in d-erythro-LacCer, the disaccharide
      moiety extends above and in the same plane as the sphingosine hydrocarbon chain,
      while in L-threo-LacCer the carbohydrate group is nearly perpendicular to the
      hydrocarbon chain. Together, these results suggest that the altered
      stereochemistry of the sphingosine group in L-threo-LacCer results in a perturbed
      structure, which is unable to pack closely with natural membrane lipids, leading
      to a reduced inclusion in plasma membrane microdomains and decreased uptake by
      caveolar endocytosis. These findings demonstrate the importance of the
      sphingolipid stereochemistry in the formation of membrane microdomains.

PMID- 16893902
TI  - A Src homology 3-binding sequence on the C terminus of Sprouty2 is necessary for
      inhibition of the Ras/ERK pathway downstream of fibroblast growth factor receptor
      stimulation.
AB  - Because the Sprouty (Spry) proteins were shown to be inhibitors of the mainstream
      Ras/ERK pathway, there has been considerable interest in ascertaining their
      mechanism of action especially since a possible role as tumor suppressors for
      these inhibitory proteins has been suggested. We compared the ability of the
      mammalian Spry isoforms to inhibit the Ras/ERK pathway in the context of
      fibroblast growth factor receptor (FGFR) signaling. Spry2 is considerably more
      inhibitory than Spry1 or Spry4, and this correlates with the binding to Grb2 via
      a C-terminal proline-rich sequence that is found exclusively on Spry2. This
      PXXPXR motif binds directly to the N-terminal Src homology domain 3 of Grb2, and
      when added onto the C terminus of Spry4 the resultant chimera inhibits the
      Ras/ERK pathway. The ability to inhibit neurite outgrowth in PC-12 cells
      correlates with the propensity of Spry isoforms and engineered constructs to
      inhibit the phosphorylation of ERK1/2. The PXXPXR motif is cryptic in
      unstimulated cells, and it is postulated that Spry2 undergoes a conformational
      change following FGFR stimulation, enabling the subsequent interaction with Grb2.
      We present evidence that Spry2 can compete with the RasGEF (guanine nucleotide
      exchange factor) SOS1 for binding to Grb2, resulting in the inhibition of
      phosphorylation of ERK1/2.

PMID- 16893903
TI  - Infertility, infertility treatment, and congenital malformations: Danish national
      birth cohort.
AB  - OBJECTIVES: To examine whether infertile couples (with a time to pregnancy of >
      12 months), who conceive naturally or after treatment, give birth to children
      with an increased prevalence of congenital malformations. DESIGN: Longitudinal
      study. SETTING: Danish national birth cohort. PARTICIPANTS: Three groups of
      liveborn children and their mothers: 50,897 singletons and 1366 twins born of
      fertile couples (time to pregnancy < or = 12 months), 5764 singletons and 100
      twins born of infertile couples who conceived naturally (time to pregnancy > 12
      months), and 4588 singletons and 1690 twins born after infertility treatment.
      MAIN OUTCOME MEASURES: Prevalence of congenital malformations determined from
      hospital discharge diagnoses. RESULTS: Compared with singletons born of fertile
      couples, singletons born of infertile couples who conceived naturally or after
      treatment had a higher prevalence of congenital malformations-hazard ratios 1.20
      (95% confidence interval 1.07 to 1.35) and 1.39 (1.23 to 1.57). The overall
      prevalence of congenital malformations increased with increasing time to
      pregnancy. When the analysis was restricted to singletons born of infertile
      couples, babies born after treatment had an increased prevalence of genital organ
      malformations (hazard ratio 2.32, 1.24 to 4.35) compared with babies conceived
      naturally. No significant differences existed in the overall prevalence of
      congenital malformations among twins. CONCLUSIONS: Hormonal treatment for
      infertility may be related to the occurrence of malformations of genital organs,
      but our results suggest that the reported increased prevalence of congenital
      malformations seen in singletons born after assisted reproductive technology is
      partly due to the underlying infertility or its determinants. The association
      between untreated infertility and congenital malformations warrants further
      examination.

PMID- 16893904
TI  - Green tea (-)-epigallocatechin-gallate modulates early events in huntingtin
      misfolding and reduces toxicity in Huntington's disease models.
AB  - Huntington's disease (HD) is a progressive neurodegenerative disorder for which
      only symptomatic treatments of limited effectiveness are available. Preventing
      early misfolding steps and thereby aggregation of the polyglutamine (polyQ)
      containing protein huntingtin (htt) in neurons of patients may represent an
      attractive therapeutic strategy to postpone the onset and progression of HD.
      Here, we demonstrate that the green tea polyphenol (-)-epigallocatechin-3-gallate
      (EGCG) potently inhibits the aggregation of mutant htt exon 1 protein in a dose
      dependent manner. Dot-blot assays and atomic force microscopy studies revealed
      that EGCG modulates misfolding and oligomerization of mutant htt exon 1 protein
      in vitro, indicating that it interferes with very early events in the aggregation
      process. Also, EGCG significantly reduced polyQ-mediated htt protein aggregation
      and cytotoxicity in an yeast model of HD. When EGCG was fed to transgenic HD
      flies overexpressing a pathogenic htt exon 1 protein, photoreceptor degeneration
      and motor function improved. These results indicate that modulators of htt exon 1
      misfolding and oligomerization like EGCG are likely to reduce polyQ-mediated
      toxicity in vivo. Our studies may provide the basis for the development of a
      novel pharmacotherapy for HD and related polyQ disorders.

PMID- 16893905
TI  - Allelic mRNA expression of X-linked monoamine oxidase a (MAOA) in human brain:
      dissection of epigenetic and genetic factors.
AB  - A pVNTR repeat polymorphism located in the promoter region of the X-linked MAOA
      gene has been associated with mental disorders. To explore the effect of
      polymorphisms and epigenetic factors on mRNA expression, we have measured allelic
      expression imbalance (AEI) in female human brain tissue, employing two frequent
      marker single nucleotide polymorphisms (SNPs) in exon 8 (T890G) and exon 14
      (C1409T) of MAOA. This approach compares one allele against the other in the same
      subject. AEI ratios ranged from 0.3 to 4 in prefrontal cortex, demonstrating the
      presence of strong cis-acting factors in mRNA expression. Analysis of CpG
      methylation in the MAOA promoter region revealed substantial methylation in
      females but not in males. MAOA methylation ratios for the three- and four-repeat
      pVNTR alleles of MAOA did not correlate with X-chromosome inactivation ratios,
      determined at the X-linked androgen receptor locus, suggesting an alternative
      process of dosage compensation in females. The extent of allelic MAOA methylation
      was highly variable and correlated with AEI (R2=0.5 and 0.7 at two CpG loci),
      indicating that CpG methylation regulates gene expression. Genetic factors
      appeared also to contribute to the AEI ratios. Genotyping of 13 MAOA
      polymorphisms in female subjects showed strong association with a haplotype block
      spanning from the pVNTR to the marker SNP. Therefore, allelic mRNA expression is
      affected by genetic and epigenetic events, both with the potential to modulate
      biogenic amine tone in the CNS.

PMID- 16893906
TI  - TBC1D1 is a candidate for a severe obesity gene and evidence for a gene/gene
      interaction in obesity predisposition.
AB  - The molecular etiology of obesity predisposition is largely unknown. Here, we
      present evidence that genetic variation in TBC1D1 confers risk for severe obesity
      in females. We identified a coding variant (R125W) in TBC1D1 that segregated with
      the disease in 4p15-14-linked obesity pedigrees. In cases derived from pedigrees
      with the strongest linkage evidence, the variant was significantly associated
      with obesity (P=0.000007) and chromosomes carrying R125W accounted for the
      majority of the evidence that originally linked 4p15-14 with the disease. In
      addition, by selecting families that segregated R125W with obesity, we were able
      to generate highly significant linkage evidence for an obesity predisposition
      locus at 4q34-35. This result provides additional and confirming evidence that
      R125W affects obesity susceptibility, delimits the location of an obesity gene at
      4q34-35 and identifies a gene/gene interaction that influences the risk for
      obesity predisposition. Finally, although the function of TBC1D1 is unknown, the
      protein is structurally similar to a known regulator of insulin-mediated Glut4
      translocation.

PMID- 16893907
TI  - Laminin alpha1 chain improves laminin alpha2 chain deficient peripheral
      neuropathy.
AB  - Absence of laminin alpha2 chain leads to a severe form of congenital muscular
      dystrophy (MDC1A) associated with peripheral neuropathy. Hence, future therapies
      should be aimed at alleviating both muscle and neurological dysfunctions. Pre
      clinical studies in animal models have mainly focused on ameliorating the muscle
      phenotype. Here we show that transgenic expression of laminin alpha1 chain in
      muscles and the peripheral nervous system of laminin alpha2 chain deficient mice
      reduced muscular dystrophy and largely corrected the peripheral nerve defects.
      The presence of laminin alpha1 chain in the peripheral nervous system resulted in
      near-normal myelination, restored Schwann cell basement membranes and improved
      rotarod performance. In summary, we postulate that laminin alpha1 chain is an
      excellent substitute for laminin alpha2 chain in multiple tissues and suggest
      that treatment with laminin alpha1 chain may be beneficial for MDC1A in humans.

PMID- 16893908
TI  - Natural transmission of USP9Y gene mutations: a new perspective on the role of
      AZFa genes in male fertility.
AB  - Deletions of the azoospermia factor (AZF) regions of the Y chromosome are
      associated with severe spermatogenic failure and represent the most frequent
      molecular genetic cause of azoospermia and severe oligozoospermia. The exact role
      of the candidate AZF genes is largely unknown due to both the extreme rarity of
      naturally occurring AZF gene-specific mutations and the lack of functional
      assays. Here, we report the fine characterization of two different deletions in
      the USP9Y gene (one of the two candidate genes in the AZFa region), which have
      been transmitted through natural conception in two unrelated families. The
      associated mild testicular phenotype, in both cases, is in sharp contrast with
      that of the two previously reported infertile patients bearing a mutation of the
      same gene. In conclusion, to date, the USP9Y gene has been considered as one of
      the major Y-linked spermatogenesis genes, based on both its position within the
      AZFa region and previous reports that correlated USP9Y mutation to severe
      spermatogenic failure and infertility. This view is now substantially changed
      because our findings clearly demonstrate that during human spermatogenesis, USP9Y
      is more likely a fine tuner that improves efficiency, rather than a provider of
      an essential function. More importantly, the observed natural conceptions suggest
      that the protein is not required for the final sperm maturation process or for
      the acquisition of sperm fertilizing ability, providing a new perspective on the
      role played by the USP9Y gene in male fertility.

PMID- 16893909
TI  - Impact of E27X, a novel CDKN2A germ line mutation, on p16 and p14ARF expression
      in Italian melanoma families displaying pancreatic cancer and neuroblastoma.
AB  - Mutations in the CDKN2A gene underlie melanoma susceptibility in as many as 50%
      of melanoma kindreds in selected populations, and several CDKN2A founder
      mutations have been described. Inherited mutations in CDKN2A have been found to
      be associated with other, non-melanoma cancers including pancreatic cancer (PC)
      and neural system tumors (NST). Here we report a novel germline mutation in exon
      1 of the CDKN2A gene, E27X, which we first detected in melanoma patients living
      in or originally from a small geographic area bordering Liguria in north-western
      Italy. A subset of melanoma kindreds positive for this mutation displayed PC and
      neuroblastoma. E27X generates a premature stop codon, leading to dramatically
      reduced protein levels of p16 and leaving p14ARF unaltered. As PC and NSTs have
      been postulated to be preferentially associated with CDKN2A mutations located in
      exon 2 and/or affecting p14ARF alone, the position of E27X in exon 1alpha
      provides interesting insights towards clarifying the mechanisms by which the
      CDKN2A/ARF locus is involved in cancer predisposition.

PMID- 16893910
TI  - Monoamine oxidase A knockout mice exhibit impaired nicotine preference but normal
      responses to novel stimuli.
AB  - Nicotine is thought to act on brain monoamine systems that normally mediate
      diverse motivational behaviors. How monoamine-related genes contribute to
      behavioral traits (e.g. responses to novel stimuli) comorbid with the
      susceptibility to nicotine addiction is still poorly understood. We examined the
      impact of constitutive monoamine oxidase A (MAOA) deficiency in mice on nicotine
      reward and responses to novel stimuli. Age-matched, male Maoa-knockout (KO) mice
      and wild-type (WT) littermates were tested for nicotine-induced conditioned place
      preference (CPP); voluntary oral nicotine preference/intake; spontaneous
      locomotor activity in a novel, inescapable open field; and novelty place
      preference. Nicotine preference in WT mice was reduced in Maoa-KO mice in the CPP
      and oral preference/intake tests. Control experiments showed that these
      phenotypes were not due to abnormalities in nicotine metabolism, fluid intake or
      response to taste. In contrast, Maoa-KO mice were normal in their behavioral
      response to a novel, inescapable open field and in their preference for a novel
      place. The observed phenotypes suggest that a constitutive deficiency of MAOA
      reduces the rewarding effects of nicotine without altering behavioral responses
      to novel stimuli in mice. Constitutive MAOA activity levels are likely to
      contribute to the vulnerability or resiliency to nicotine addiction by altering
      the rewarding effects of nicotine.

PMID- 16893911
TI  - Neurofibromin plays a critical role in modulating osteoblast differentiation of
      mesenchymal stem/progenitor cells.
AB  - Mutations in the NF1 tumor suppressor gene cause neurofibromatosis type 1, a
      pandemic autosomal dominant genetic disorder with an incidence of 1:3000.
      Individuals with NF1 have a variety of malignant and non-malignant
      manifestations, including skeletal manifestations, such as osteoporosis,
      scoliosis and short statures. However, the mechanism(s) underlying the osseous
      manifestations in NF1 are poorly understood. In the present study, utilizing Nf1
      haploinsufficient (+/-) mice, we demonstrate that Nf1+/- mesenchymal
      stem/progenitor cells (MSPC) have increased proliferation and colony forming unit
      fibroblast (CFU-F) capacity compared with wild-type (WT) MSPC. Nf1+/- MSPC also
      have fewer senescent cells and have a significantly higher telomerase activity
      compared with WT MSPC. Nf1+/- MSPC have impaired osteoblast differentiation as
      determined by alkaline phosphatase staining, and confirmed by single CFU-F
      replating assays. The impaired osteoblast differentiation in Nf1+/- MSPC is
      consistent with the reduced expression of osteoblast markers at the mRNA level,
      including osteocalcin and osteonectin. Importantly, re-expression of the full
      length NF1 GTPase activating related domain (NF1 GAP-related domain) is
      sufficient to restore the impaired osteoblast differentiation in Nf1+/- MSPC.
      Taken together, our results suggest that neurofibromin plays a crucial role in
      modulating MSPC differentiation into osteoblasts, and the defect in osteoblast
      differentiation may contribute at least in part to the osseous abnormalities seen
      in individuals with NF1.

PMID- 16893912
TI  - Analysis of epistasis for diabetic nephropathy among type 2 diabetic patients.
AB  - Diabetic nephropathy (DN) is one of the most serious complications of diabetes,
      accounting for the majority of patients with end-stage renal disease. The
      molecular pathogenesis of DN involves multiple pathways in a complex, partially
      resolved manner. The paper presents an exploratory epistatic study for DN.
      Association analysis were performed on 231 SNP loci in a cohort of 264 type 2
      diabetes patients, followed by the epistasis analysis using the multifactor
      dimensionality reduction and the genetic algorithm with Boolean algebra. A two
      locus epistatic effect of EGFR and RXRG was identified, with a cross-validation
      consistency of 91.7%.

PMID- 16893913
TI  - The microtubule-severing protein Spastin is essential for axon outgrowth in the
      zebrafish embryo.
AB  - Hereditary spastic paraplegia (HSP) is a collection of neurological disorders
      characterized by developmental failure or degeneration of motor axons in the
      corticospinal tract and progressive lower limb spasticity. SPG4 mutations are the
      most common cause of autosomal dominant HSP and Spastin (the SPG4 gene product)
      is a microtubule severing protein that shares homology with katanin, the
      microtubule severing activity of which promotes axon growth in cultured neurons.
      Given the sequence and functional similarity between spastin and katanin, we
      hypothesized that spastin promotes the dynamic disassembly and remodelling of
      microtubules required for robust, properly directed motor axon outgrowth. To
      investigate this hypothesis, we cloned the zebrafish spg4 orthologue and used
      morpholino antisense oligonucleotides directed against the translation start site
      and the intron 7-8 splice donor site to knock down spastin function in the
      developing zebrafish embryo. Reduced spg4 function caused dramatic defects in
      motor axon outgrowth without affecting the events driving the initial
      specification of motor neurones. Other neuronal subtypes also exhibited a
      requirement for spg4 function, since spg4 knock down caused both widespread
      defects in neuronal connectivity and extensive CNS-specific apoptosis. Our
      results reveal a critical requirement for spastin to promote axonal outgrowth
      during embryonic development, and they validate the zebrafish embryo as a novel
      model system to dissect the pathogenetic mechanisms underlying HSP. Taken
      together with other recent studies, our findings suggest that axon outgrowth
      defects may be a common feature of childhood SPG3A and SPG4 cases.

PMID- 16893914
TI  - Identification of the transcription factor ARNTL2 as a candidate gene for the
      type 1 diabetes locus Idd6.
AB  - The Idd6 murine type 1 diabetes locus has been shown to control diabetes by
      regulating the protective activity of the peripheral immune system, as
      demonstrated by diabetes transfer assays using splenocytes. The analysis of three
      novel subcongenic (NOD.C3H nonobese. C3H) diabetes strains has confirmed the
      presence of at least two diabetes-related genes within the 5.8 Mb Idd6 interval
      with the disease protection conferred by splenocyte co-transfer being located to
      the 700 kb Idd6.3 subregion. This subinterval contains the circadian rhythm
      related transcription factor Arntl2 (Bmal2), a homologue of the type 2 diabetes
      associated ARNT (HIF1beta) gene. Arntl2 exhibited a six-fold upregulation in
      spleens of the NOD.C3H 6.VIII congenic strain compared with the NOD control
      strain, strain-specific splice variants and a large number of polymorphisms in
      both coding and non-coding regions. Arntl2 upregulation was not associated with
      changes in the expression levels of other circadian genes in the spleen, but did
      correlate with the upregulation of the ARNT-binding motif containing Pla2g4a
      gene, which has recently been described as being protective for the progression
      of insulitis and autoimmune diabetes in the NOD mouse via regulation of the
      tumour necrosis factor-alpha pathway. Our studies strongly suggest that the
      HIFbeta-homologous Arntl2 gene is involved in the control of type 1 diabetes.

PMID- 16893915
TI  - Peptide and protein profiles in serum and follicular fluid of women undergoing
      IVF.
AB  - BACKGROUND: Proteins and peptides in human follicular fluid originate from plasma
      or are produced by follicular structures. Compositional changes reflect oocyte
      maturation and can be used as diagnostic markers. The aim of the study was to
      determine protein and peptide profiles in paired serum and follicular fluid
      samples from women undergoing IVF. METHODS: Surface-enhanced laser desorption and
      ionization-time of flight-mass spectrometry (SELDI-TOF-MS) was used to obtain
      characteristic protein pattern. RESULTS: One hundred and eighty-six individual MS
      signals were obtained from a combination of enrichment on strong anion exchanger
      (110), weak cation exchanger (52) and normal phase surfaces (24). On the basis of
      molecular masses, isoelectric points and immunoreactivety, four signals were
      identified as haptoglobin (alpha(1)- and alpha(2)-chain), haptoglobin 1 and
      transthyretin (TTR). Immunological and MS characteristics of the TTR : retinol
      binding protein (RBP) transport complex revealed no microheterogeneity
      differences between serum and follicular fluid. Discriminatory patterns arising
      from decision-tree-based classification and regression analysis distinguished
      between serum and follicular fluid with a sensitivity and specificity of 100%.
      CONCLUSIONS: Quantitative and qualitative differences indicate selective
      transport processes rather than mere filtration across the blood-follicle
      barrier. Identified proteins as well as characteristic peptide and/or protein
      signatures might emerge as potential candidates for diagnostic markers of
      follicle and/or oocyte maturation and thus oocyte quality.

PMID- 16893916
TI  - Impact of gonadotrophins and steroid hormones on tumour cells derived from
      borderline ovarian tumours.
AB  - BACKGROUND: Conservative surgery is currently proposed for young patients with
      borderline ovarian tumours (BOT). For those experiencing infertility, the
      question of medically assisted procreation is raised. We have evaluated in vitro
      the proliferation of cultured BOT cells in response to FSH or estradiol (E(2)).
      METHODS: Primary cell cultures were prepared from BOT. The presence of FSH and
      E(2) receptors was evaluated by immunochemistry. Cultures in vitro were
      stimulated with FSH (40 and 200 mUI/ml) or E(2) (300 and 2000 pg/ml) for 96 h and
      proliferation was evaluated with the WST-1 test. RESULTS: Four primary cultures
      were obtained that expressed FSH and E(2) receptors to different extents. Growth
      was generally similar to controls when treated with either FSH or E(2) although
      300 pg/ml E(2) caused a significant inhibitory effect on cell proliferation (P =
      0.035). CONCLUSION: No stimulatory effect of FSH or E(2) on cultured BOT cells
      was found, despite the presence of receptors. Although preliminary, these results
      suggest that gonadotrophins and E(2) could be used in patients experiencing
      infertility after conservative surgery.

PMID- 16893917
TI  - Impact of urban atmospheric pollution on coronary disease.
AB  - Recent epidemiological findings have suggested that urban atmospheric pollution
      may have adverse effects on the cardiovascular system as well as on the
      respiratory system. We carried out an exhaustive search of published studies
      investigating links between coronary heart disease and urban atmospheric
      pollution. The review was conducted on cited articles published between 1994 and
      2005 and whose main objective was to measure the risk of ischaemic heart diseases
      related to urban pollution. Of the 236 references identified, 46 epidemiological
      studies were selected for analysis on the basis of pre-defined criteria. The
      studies were analysed according to short-term effects (time series and case
      crossover designs) and long-term effects (case-control and cohort studies). A
      link between coronary heart disease and at least one of the pollutants studied
      (PM10, O3, NOx, CO, SO2) emerged in 40 publications. Particulate matter, nitrogen
      oxides, and carbon monoxide were the pollutants most often linked with coronary
      heart disease. The association was inconstant for O3. Although the mean mortality
      or morbidity risk related to urban atmospheric pollution is low compared with
      that associated with other better-known risk factors, its impact on health is
      nevertheless major because of the large number of people who are exposed. This
      exhaustive review supports the possibility that urban pollution is indeed an
      environmental cardiovascular risk factor and should be considered as such by the
      cardiologists.

PMID- 16893918
TI  - Angioscopic differences in neointimal coverage and in persistence of thrombus
      between sirolimus-eluting stents and bare metal stents after a 6-month
      implantation.
AB  - AIMS: The neointimal coverage and intracoronary thrombi within stented segments
      at 6 months after implantation between sirolimus-eluting stents (SESs) and bare
      metal stents (BMSs) were compared by direct visualization using angioscopy.
      METHODS AND RESULTS: Forty-six patients (36 stable angina and 10 acute coronary
      syndrome) were treated with 33 SESs and 33 BMSs. Immediately after and 6 months
      after stenting, each of the stented segments, edge body, and overlapping segment
      were observed by angioscopy and the grade of neointimal coverage over the stents
      was classified as 0: absent neointima, 1: visible struts through thin neointima,
      or 2: invisible struts. The existence of thrombi was also evaluated. The average
      grade of the neointimal coverage at 6 months follow-up was lower in the SES than
      that in the BMS (edge: 1.4+/-0.7 vs. 1.9+/-0.2, body: 1.0+/-0.5 vs. 1.8+/-0.5,
      overlapping segment: 0.6+/-0.7 vs. 1.8+/-0.5; P<0.0001, P<0.0001, P=0.0069,
      respectively). The frequency of persistence of thrombus was significantly higher
      in the SESs than that in the BMSs (86 vs. 29%, respectively; P=0.031).
      CONCLUSION: The present study suggested a delayed neointimal stent coverage and
      slower thrombus disappearance process in the SESs in comparison to the BMSs.

PMID- 16893919
TI  - Inhibition of angiotensin II type 1 receptors reduces atrial stunning and
      spontaneous echo contrast after electrical cardioversion of atrial fibrillation.

PMID- 16893920
TI  - Arrhythmogenic right ventricular cardiomyopathy caused by deletions in
      plakophilin-2 and plakoglobin (Naxos disease) in families from Greece and Cyprus:
      genotype-phenotype relations, diagnostic features and prognosis.
AB  - AIMS: To evaluate clinical disease expression, non-invasive diagnosis, and
      prognosis in families with dominant vs. recessive arrhythmogenic right
      ventricular cardiomyopathy (ARVC) due to mutations in related desmosomal proteins
      plakophilin-2 (PKP2) and plakoglobin (JUP), respectively. METHODS AND RESULTS:
      One hundred and eighty-seven individuals belonging to ARVC families, four with
      dominant PKP2 mutations and 12 with recessive JUP mutation underwent serial non
      invasive cardiac assessment. Survival and arrhythmic events were evaluated
      prospectively up to 21 years (median 8.5 years). Sixteen of 22 PKP2 carriers and
      all 26 homozygous JUP carriers fulfilled the diagnostic criteria for ARVC, the
      youngest by the age of 13 years. Clinical disease expression did not differ
      significantly between PKP2 and JUP carriers. T-wave inversion in leads V1-V3,
      right ventricular wall motion abnormalities, and frequent ventricular
      extrasystoles were the most sensitive/specific markers for identification of
      mutation carriers. QRS dispersion > or =40 ms was an independent predictor of
      syncope but not of sudden death. CONCLUSION: Mutations in PKP2 and JUP express
      similar cardiac phenotype. Non-invasive family screening may largely be based on
      T-wave inversion, right ventricular wall motion abnormalities, and frequent
      ventricular extrasystoles to identify mutation carriers.

PMID- 16893921
TI  - Implications of small effect sizes of individual genetic variants on the design
      and interpretation of genetic association studies of complex diseases.
AB  - Accumulated evidence from searching for candidate gene-disease associations of
      complex diseases can offer some insights as the field moves toward discovery
      oriented approaches with massive genome-wide testing. Meta-analyses of 50 non
      human lymphocyte antigen gene-disease associations with documented overall
      statistical significance (752 studies) show summary odds ratios with a median of
      1.43 (interquartile range, 1.28-1.65). Many different biases may operate in this
      field, for both single studies and meta-analyses, and these biases could
      invalidate some of these seemingly "validated" associations. Studies with a
      sample size of >500 show a median odds ratio of only 1.15. The median sample size
      required to detect the observed summary effects in each population addressed in
      the 752 studies is estimated to be 3,535 (interquartile range, 1,936-9,119 for
      cases and controls combined). These estimates are steeply inflated in the
      presence of modest bias. Population heterogeneity, as well as gene-gene and gene
      environment interactions, could steeply increase these estimates and may be
      difficult to address even by very large biobanks and observational cohorts. The
      one visible solution is for a large number of teams to join forces on the same
      research platforms. These collaborative studies ideally should be designed up
      front to also assess more complex gene-gene and gene-environment interactions.

PMID- 16893922
TI  - ZIP-code-based versus tract-based income measures as long-term risk-adjusted
      mortality predictors.
AB  - There is a well-established, strong association between socioeconomic position
      and mortality. Public health mortality analyses thus routinely consider the
      confounding effect of socioeconomic position when possible. Particularly in the
      absence of personally reported data, researchers often use area-based measures to
      estimate the effects of socioeconomic position. Data are limited regarding the
      relative merits of measures based on US Census tract versus ZIP code (postal
      code). ZIP-code measures have more within-unit variation but are also more easily
      obtained. The current study reports on 293,138 middle-aged men screened in 14
      states in 1973-1975 for the Multiple Risk Factor Intervention Trial and having 25
      year mortality follow-up. In risk-adjusted proportional hazards models containing
      either ZIP-code-based or tract-based median household income, all-cause mortality
      hazard ratios were 1.16 (95% confidence interval: 1.14, 1.17) per Dollars 10,000
      less ZIP-code-based income and 1.15 (95% confidence interval: 1.13, 1.16) per
      Dollars 10,000 less tract-based income; adding either income variable to a risk
      adjusted model improved model fit substantially. Both were significant
      independent predictors in a combined model; tract-based income was a slightly
      stronger mortality predictor (hazard ratios = 1.05 and 1.11 for ZIP-code-based
      and tract-based income, respectively). These patterns held across various causes
      of death, for both Blacks and non-Blacks, and with or without adjustment for ZIP
      code-based income diversity or tract-based proportion below poverty.

PMID- 16893923
TI  - Peptide p277 of HSP60 signals T cells: inhibition of inflammatory chemotaxis.
AB  - Peptide p277 is a 24-amino acid fragment of the heat shock protein 60 molecule,
      first discovered to be an antigen for diabetogenic T-cell clones in non-obese
      diabetic (NOD) mice. Therapeutic vaccination with p277 can arrest the spontaneous
      diabetogenic process both in NOD mice and in humans associated with a T(h)1 to
      T(h)2 cytokine shift specific for the autoimmune T cells. We now report that p277
      can directly signal human T cells via innate toll-like receptor (TLR)-2, leading
      to up-regulation of integrin-mediated adhesion to fibronectin, and inhibition of
      chemotaxis to the chemokine SDF-1alpha in vitro. Resting CD45RA(+) T cells
      responded to lower concentrations of p277 than resting CD45RO(+) T cells, but
      activation of CD45RO(+) T cells greatly increased their sensitivity to p277.
      Mouse T cells, but not macrophages, were also sensitive to the innate effects of
      peptide p277, and adoptive transfer of diabetes by splenic T cells from NOD mice
      could be inhibited by p277 treatment before transfer. Thus, T cells do respond
      innately to p277, and signaling by soluble p277 through TLR2 could contribute to
      the treatment of type 1 diabetes; p277 may stop the destruction of beta cells by
      signaling in concert both innate and adaptive receptors on T cells.

PMID- 16893924
TI  - The TCR Vbeta signature of bacterial superantigens spreads with stimulus
      strength.
AB  - Superantigens (Sags) induce large-scale stimulation of T lymphocytes by a
      mechanism distinct from conventional antigen presentation, involving direct MHC
      binding and stimulation of TCR families based on Vbeta gene usage. The specific
      Vbeta targets of a given Sag have, since the earliest studies in murine models,
      been considered a hallmark of that toxin. Bacterial Sags are implicated in the
      aetiology of a wide range of human diseases, although their role has been most
      clearly defined in toxic shock syndrome. While Sags have been defined by the
      Vbeta-specific changes in T cell repertoire they induce, human studies of in
      vitro stimulation or analysis of cells from infected patients have produced
      inconsistent findings. Here we have evaluated the contribution of HLA allelic
      polymorphisms and strength of stimulus to this response. We show that there are
      differences in binding and presentation of the staphylococcal Sag, staphylococcal
      enterotoxin A (SEA), by different HLA-DR alleles. We also show that the TCR Vbeta
      response, previously thought to be a fixed property defining a given Sag, varies
      with stimulus strength such that a broader repertoire of response is seen at
      higher concentrations or following presentation by high-binding class II types.
      Responses of human Vbeta8 and Vbeta1 to SEA, Vbeta5 to SEB and of Vbeta12 and
      Vbeta13 to streptococcal pyrogenic exotoxin A are absolutely dependent on
      stimulus strength. These findings have important implications for heterogeneity
      in the response to Sags and the consequent differences in susceptibility to
      severe toxic shock.

PMID- 16893926
TI  - Lapses at the new England journal of medicine.

PMID- 16893927
TI  - Long-acting bronchodilators: time for a re-think.

PMID- 16893928
TI  - Peer review. Peerless review.

PMID- 16893929
TI  - Too little quality; too many doctors.

PMID- 16893930
TI  - Non-traumatic rhabdomyolysis: the emerging role of CYP 3A4 in diabetes mellitus.

PMID- 16893931
TI  - Conflicts of interest that are bigger than money but never disclosed.

PMID- 16893932
TI  - Peer review. Unreliable reviewers.

PMID- 16893934
TI  - Bilateral chronic subdural haematoma.

PMID- 16893933
TI  - Medical theories on the cause of death in crucifixion.

PMID- 16893935
TI  - Diagnosing malaria in UK migrants from sub-Saharan Africa.

PMID- 16893936
TI  - Plague, rats and the Bible again.

PMID- 16893937
TI  - Hypertrophic pulmonary osteoarthropathy and the vagus nerve: an historical note.

PMID- 16893938
TI  - Rickets and the Fairfax family receipt books.

PMID- 16893939
TI  - Impact of iodination on thyroid pathology in Africa.

PMID- 16893940
TI  - Walking, cycling and transport safety: an analysis of child road deaths.
AB  - OBJECTIVE: To examine trends in road death rates for child pedestrians, cyclists
      and car occupants. DESIGN: Analysis of road traffic injury death rates per 100
      000 children and death rates per 10 million passenger miles travelled. SETTING:
      England and Wales between 1985 and 2003. PARTICIPANTS: Children aged 0-14 years.
      INTERVENTIONS: None. MAIN OUTCOME MEASURES: Death rates per 100,000 children and
      per 10 million child passenger miles for pedestrians, cyclists and car occupants.
      RESULTS: Death rates per head of population have declined for child pedestrians,
      cyclists and car occupants but pedestrian death rates remain higher (0.55
      deaths/100,000 children; 95% confidence interval [CI] 0.42 to 0.72 deaths) than
      those for car occupants (0.34 deaths; 95% CI 0.23 to 0.48 deaths) and cyclists
      (0.16 deaths; 95% CI 0.09 to 0.27 deaths). Since 1985, the average distance
      children travelled as a car occupant has increased by 70%; the average distance
      walked has declined by 19%; and the average distance cycled has declined by 58%.
      Taking into account distance travelled, there are about 50 times more child
      cyclist deaths (0.55 deaths/10 million passenger miles; 0.32 to 0.89) and nearly
      30 times more child pedestrian deaths (0.27 deaths; 0.20 to 0.35) than there are
      deaths to child car occupants (0.01 deaths; 0.007 to 0.014). In 2003, children
      from families without access to a vehicle walked twice the distance walked by
      children in families with access to two or more vehicles. CONCLUSIONS: More needs
      to be done to reduce the traffic injury death rates for child pedestrians and
      cyclists. This might encourage more walking and cycling and also has the
      potential to reduce social class gradients in injury mortality.

PMID- 16893941
TI  - Identifying patients at high risk of emergency hospital admissions: a logistic
      regression analysis.
AB  - OBJECTIVE: To use routine data to identify patients at high risk of future
      emergency hospital admissions. DESIGN: Descriptive analysis of inpatient hospital
      episode statistics. Predictive model developed using multiple logistic
      regression. SETTING: National Health Service hospital trusts in England.
      PARTICIPANTS: All patients with an emergency admission to an NHS hospital between
      1 April 2000 and 31 March 2001. MAIN OUTCOME MEASURES: 'High-impact users' were
      defined as patients who had at least one emergency inpatient admission and who
      then went on to have at least two further emergency hospital admissions in the 12
      months following the start date of that index admission. RESULTS: 2,895,234
      patients were admitted as emergencies in 2000/2001, of whom 147,725 (5.1%) did
      not survive their first spell. Of the 2,747,509 surviving patients, 269,686
      (9.8%) subsequently had at least two or more emergency admissions within 365 days
      of the index date of admission. A further 236,779 (8.6%) died during this period.
      Risk factors for becoming a high-impact user included the number of emergencies
      in the 36 months before index spell, comorbidity, age, an admission for an
      ambulatory care sensitive condition, ethnicity, area-level socioeconomic data,
      local admission rates, the number of episodes in the index spell, sex and the
      source of admission. The predictive model based on all emergency admissions
      produced a receiver operating characteristic curve score of 0.72. CONCLUSIONS:
      Routine hospital episode statistics can be used to identify patients who are at
      high risk of suffering future multiple emergency hospital admissions. The
      potential cost savings in preventing a proportion of these subsequent admissions
      need to be compared with the costs of case management of these patients.

PMID- 16893942
TI  - Relapsing and remitting insulin requiring diabetes: type 1 or type 2?

PMID- 16893944
TI  - Reflections on my studies of the effects of sulphonamide drugs in bacillary
      dysentery in Egypt, 1943-1944.

PMID- 16893945
TI  - Surviving hurricane Wilma.

PMID- 16893943
TI  - When a normal hearing test is just the beginning.

PMID- 16893946
TI  - Return to work after ill-health retirement in Scottish NHS staff and teachers.
AB  - BACKGROUND: Most major public and private sector pension schemes have provision
      for ill-health retirement (IHR) for those who become too ill to continue to work
      before their normal retirement age. AIM: To compare the causes, process and
      outcomes of IHR in teachers and National Health Service (NHS) staff in Scotland.
      METHODS: A total of 537 teachers and 863 NHS staff who retired due to ill-health
      between April 1998 and March 2000 were mailed an IHR questionnaire by the
      Scottish Public Pensions Agency. RESULTS: The response rate for teachers was 53%
      and for NHS staff 49%. The most common cause of IHR was musculoskeletal disorders
      for NHS staff and mental disorders for teachers. Teachers retired at a younger
      average age than NHS staff. Ninety-two per cent of NHS staff but only 11% of
      teachers attended occupational health services (OHS) prior to IHR. Eighteen per
      cent of NHS staff and 9% of teachers were offered part-time work by their current
      employer in response to their ill-health. Fifteen per cent of NHS staff and 5% of
      teachers were offered alternative work prior to retirement. Seventeen per cent of
      NHS staff and 36% of teachers subsequently found employment. Multiple logistic
      regression analyses showed the following variables as independent predictors of
      subsequent employment: occupational group, age group, sex, managerial
      responsibility and cause of IHR. CONCLUSIONS: Return to work after IHR suggests
      that some IHR could be avoided. Teachers had a higher rate of return to work and
      much less access to OHS.

PMID- 16893947
TI  - Density of dendritic cells in the human tracheal mucosa is age dependent and site
      specific.
AB  - BACKGROUND: The mucosal immune system undergoes extensive changes in early
      childhood in response to environmental stimuli. Dendritic cells (DC) play a major
      role in the development of the immune system. However, few data exist on the
      influence of continuous environmental stimulation on the distribution and
      phenotype of human airway DC. METHODS: Human tissue samples are mostly paraffin
      embedded which limits the use of several antibodies, and respiratory tissue for
      cryopreservation is difficult to obtain. Human frozen post mortem tracheal tissue
      was therefore used for this study. Only samples with epithelial adherence to the
      basement membrane were included (n = 34). Immunohistochemical staining and
      sequential overlay immunofluorescence were performed with DC-SIGN and a panel of
      leucocyte markers co-expressed by DC. RESULTS: DC detected in the human tracheal
      mucosa using DC-SIGN correlated with the expression of HLA-DR, co-stimulatory and
      adhesion molecules. Higher cell densities were found at the ventral tracheal site
      of patients older than 1 year than in infants in the first year of life.
      CONCLUSION: The increasing population of mucosal DC with age could reflect
      immunological maturation.

PMID- 16893949
TI  - Association of genetic variations in neurokinin-2 receptor with enhanced cough
      sensitivity to capsaicin in chronic cough.
AB  - BACKGROUND: Chronic cough is associated with increased sensitivity to inhaled
      capsaicin, and both tachykinins and their receptors play important roles in the
      cough reflex. However, associations between polymorphisms of the tachykinin
      receptor genes and cough sensitivity in patients with non-productive chronic
      cough have not been reported. METHODS: Direct sequencing was used to identify
      single nucleotide polymorphisms (SNPs) in the genes for the neurokinin-1 and
      neurokinin-2 receptors (NK-1R and NK-2R, respectively). Informative non
      synonymous SNPs were scored using the single base extension method for 312
      patients with chronic cough and for 100 age matched healthy controls. The cough
      response to capsaicin was recorded for 312 patients with chronic cough, and the
      potential genetic association between cough sensitivity to capsaicin and the NK
      1R and NK-2R genotypes was evaluated. RESULTS: Two informative SNPs were
      identified in NK-2R (Gly231Glu and Arg375His), whereas no informative SNP was
      found in NK-1R. After adjusting for atopy, sex, age, and smoking, the prevalence
      of enhanced cough sensitivity to capsaicin was higher in the chronic cough
      patients with the 231Glu allele (p = 0.004; OR 1.69 (95% CI 1.18 to 2.42)) and
      the 231Glu_375Arg haplotype (p = 0.003; OR 1.71 (95% CI 1.20 to 2.24)). Moreover,
      the lowest capsaicin concentration to cause five consecutive coughs (C5) was
      significantly lower in patients with 231Glu (mean (SD) 44.1 (53.2) v 60.9 (55.8)
      microM/l, p = 0.04) and those with 231Glu_375Arg (43.2 (52.7) v 69.6 (52.0)
      microM/l, p = 0.03). CONCLUSIONS: The results of this study suggest that NK-2R
      gene polymorphisms are involved in the enhanced cough sensitivity to capsaicin of
      patients with chronic cough.

PMID- 16893948
TI  - Airway hyperresponsiveness and risk of chest symptoms in an occupational model.
AB  - BACKGROUND: The clinical outcome of asymptomatic airway hyperresponsiveness (AHR)
      remains unclear. A study was undertaken to evaluate the incidence of respiratory
      symptoms in a cohort of asymptomatic subjects with AHR at baseline. METHODS: A 3
      year prospective study involving methacholine challenge tests and serially
      administered questionnaires was undertaken in 769 apprentices exposed to high
      molecular weight allergens. Analyses were performed on 428 initially asymptomatic
      subjects. RESULTS: Thirty eight subjects (8.9%) were airway hyperresponsive
      (PC(20) < or =8 mg/ml) and asymptomatic at the start of the study. Forty four
      apprentices (10.3%) developed two or more respiratory symptoms unrelated to work,
      13 (34.2%) in the AHR group and 31 (7.9%) in the non-AHR group (risk ratio (RR)
      7.88 (95% CI 2.53 to 24.55) among subjects with AHR). The RR of developing two or
      more respiratory symptoms increased as the degree of PC(20) decreased with a
      significant trend (p<0.001). In a multivariate analysis, AHR (RR 8.33, 95% CI
      2.65 to 26.16) and self-reported rhinitis on exposure to pollen through an
      interaction with a family history of asthma (RR 6.3, 95% CI 1.29 to 31.89) were
      associated with the incidence of two or more respiratory symptoms; atopy was not
      a significant covariate. CONCLUSION: AHR in asymptomatic subjects is an important
      determinant for the development of respiratory symptoms outside the workplace
      among apprentices exposed to high molecular weight allergens in their training
      environment.

PMID- 16893950
TI  - Engineering a high-affinity methyl-CpG-binding protein.
AB  - Core members of the MBD protein family (MeCP2, MBD1, MBD2 and MBD4) share a
      methyl-CpG-binding domain that has a specific affinity for methylated CpG sites
      in double-stranded DNA. By multimerizing the MDB domain of Mbd1, we engineered a
      poly-MBD protein that displays methyl-CpG-specific binding in vitro with a
      dissociation constant that is >50-fold higher than that of a monomeric MBD. Poly
      MBD proteins also localize to methylated foci in cells and can deliver a
      functional domain to reporter constructs in vivo. We propose that poly-MBD
      proteins are sensitive reagents for the detection of DNA methylation levels in
      isolated native DNA and for cytological detection of chromosomal CpG methylation.

PMID- 16893951
TI  - Simultaneous amplification and screening of whole plasmids using the T7
      bacteriophage replisome.
AB  - This study describes a novel helicase-mediated isothermal DNA amplification
      method that exponentially amplifies circular DNAs. The circular helicase
      dependent amplification (cHDA) system is based on the T7 replication machinery,
      which includes the processive T7 helicase, an exonuclease-deficient T7 DNA
      polymerase (T7 Sequenase) and the T7 Gp2.5 single-stranded DNA-binding (SSB)
      protein. After the duplex DNA template is unwound by the T7 helicase, specific
      primers anneal to the separated DNA strands and T7 Sequenase extends the 3' end
      of each primer by a rolling circle mechanism to amplify not only a region defined
      by the primers but also continuous concatemers of the template. The cHDA reaction
      can be carried out at one temperature (25 degrees C) for the entire process and
      can achieve up to 10 000-fold amplification. Amplification can be performed using
      purified plasmid DNA or a crude cell lysate and can amplify inserts as large as
      10 kb. Following a cHDA reaction, the amplified products can be used directly for
      sequencing and restriction enzyme digestion without further purification. By
      utilizing the helicase enzyme, circular DNA samples can be simultaneously
      screened and amplified at one constant temperature in one easy step.

PMID- 16893952
TI  - High-throughput discovery of rare human nucleotide polymorphisms by Ecotilling.
AB  - Human individuals differ from one another at only approximately 0.1% of
      nucleotide positions, but these single nucleotide differences account for most
      heritable phenotypic variation. Large-scale efforts to discover and genotype
      human variation have been limited to common polymorphisms. However, these efforts
      overlook rare nucleotide changes that may contribute to phenotypic diversity and
      genetic disorders, including cancer. Thus, there is an increasing need for high
      throughput methods to robustly detect rare nucleotide differences. Toward this
      end, we have adapted the mismatch discovery method known as Ecotilling for the
      discovery of human single nucleotide polymorphisms. To increase throughput and
      reduce costs, we developed a universal primer strategy and implemented algorithms
      for automated band detection. Ecotilling was validated by screening 90 human DNA
      samples for nucleotide changes in 5 gene targets and by comparing results to
      public resequencing data. To increase throughput for discovery of rare alleles,
      we pooled samples 8-fold and found Ecotilling to be efficient relative to
      resequencing, with a false negative rate of 5% and a false discovery rate of 4%.
      We identified 28 new rare alleles, including some that are predicted to damage
      protein function. The detection of rare damaging mutations has implications for
      models of human disease.

PMID- 16893953
TI  - The outcomes of pathway database computations depend on pathway ontology.
AB  - Different biological notions of pathways are used in different pathway databases.
      Those pathway ontologies significantly impact pathway computations. Computational
      users of pathway databases will obtain different results depending on the pathway
      ontology used by the databases they employ, and different pathway ontologies are
      preferable for different end uses. We explore differences in pathway ontologies
      by comparing the BioCyc and KEGG ontologies. The BioCyc ontology defines a
      pathway as a conserved, atomic module of the metabolic network of a single
      organism, i.e. often regulated as a unit, whose boundaries are defined at high
      connectivity stable metabolites. KEGG pathways are on average 4.2 times larger
      than BioCyc pathways, and combine multiple biological processes from different
      organisms to produce a substrate-centered reaction mosaic. We compared KEGG and
      BioCyc pathways using genome context methods, which determine the functional
      relatedness of pairs of genes. For each method we employed, a pair of genes
      randomly selected from a BioCyc pathway is more likely to be related by that
      method than is a pair of genes randomly selected from a KEGG pathway, supporting
      the conclusion that the BioCyc pathway conceptualization is closer to a single
      conserved biological process than is that of KEGG.

PMID- 16893954
TI  - Protein binding site prediction using an empirical scoring function.
AB  - Most biological processes are mediated by interactions between proteins and their
      interacting partners including proteins, nucleic acids and small molecules. This
      work establishes a method called PINUP for binding site prediction of monomeric
      proteins. With only two weight parameters to optimize, PINUP produces not only
      42.2% coverage of actual interfaces (percentage of correctly predicted interface
      residues in actual interface residues) but also 44.5% accuracy in predicted
      interfaces (percentage of correctly predicted interface residues in the predicted
      interface residues) in a cross validation using a 57-protein dataset. By
      comparison, the expected accuracy via random prediction (percentage of actual
      interface residues in surface residues) is only 15%. The binding sites of the 57
      protein set are found to be easier to predict than that of an independent test
      set of 68 proteins. The average coverage and accuracy for this independent test
      set are 30.5 and 29.4%, respectively. The significant gain of PINUP over expected
      random prediction is attributed to (i) effective residue-energy score and
      accessible-surface-area-dependent interface-propensity, (ii) isolation of
      functional constraints contained in the conservation score from the structural
      constraints through the combination of residue-energy score (for structural
      constraints) and conservation score and (iii) a consensus region built on top
      ranked initial patches.

PMID- 16893955
TI  - The roles of specific glycosylases in determining the mutagenic consequences of
      clustered DNA base damage.
AB  - The potential for genetic change arising from specific single types of DNA lesion
      has been thoroughly explored, but much less is known about the mutagenic effects
      of DNA lesions present in clustered damage sites. Localized clustering of damage
      is a hallmark of certain DNA-damaging agents, particularly ionizing radiation. We
      have investigated the potential of a non-mutagenic DNA base lesion, 5,6
      dihydrothymine (DHT), to influence the mutagenicity of 8-oxo-7,8-dihydroguanine
      (8-oxoG) when the two lesions are closely opposed. Using a bacterial plasmid
      based assay we present the first report of a significantly higher mutation
      frequency for the clustered DHT and 8-oxoG lesions than for single 8-oxoG in wild
      type and in glycosylase-deficient strains. We propose that endonuclease III has
      an important role in the initial stages of processing DHT/8-oxoG clusters,
      removing DHT to give an intermediate with an abasic site or single-strand break
      opposing 8-oxoG. We suggest that this mutagenic intermediate is common to several
      different combinations of base lesions forming clustered DNA damage sites. The
      MutY glycosylase, acting post-replication, is most important for reducing
      mutation formation. Recovered plasmids commonly gave rise to both wild-type and
      mutant progeny, suggesting that there is differential replication of the two DNA
      strands carrying specific forms of base damage.

PMID- 16893956
TI  - Role of ATP hydrolysis in the DNA translocase activity of the bovine
      papillomavirus (BPV-1) E1 helicase.
AB  - The E1 protein of bovine papillomavirus type-1 is the viral replication initiator
      protein and replicative helicase. Here we show that the C-terminal approximately
      300 amino acids of E1, that share homology with members of helicase superfamily 3
      (SF3), can act as an autonomous helicase. E1 is monomeric in the absence of ATP
      but assembles into hexamers in the presence of ATP, single-stranded DNA (ssDNA)
      or both. A 16 base sequence is the minimum for efficient hexamerization, although
      the complex protects approximately 30 bases from nuclease digestion, supporting
      the notion that the DNA is bound within the protein complex. In the absence of
      ATP, or in the presence of ADP or the non-hydrolysable ATP analogue AMP-PNP, the
      interaction with short ssDNA oligonucleotides is exceptionally tight (T(1/2) > 6
      h). However, in the presence of ATP, the interaction with DNA is destabilized
      (T(1/2) approximately 60 s). These results suggest that during the ATP hydrolysis
      cycle an internal DNA-binding site oscillates from a high to a low-affinity
      state, while protein-protein interactions switch from low to high affinity. This
      reciprocal change in protein-protein and protein-DNA affinities could be part of
      a mechanism for tethering the protein to its substrate while unidirectional
      movement along DNA proceeds.

PMID- 16893957
TI  - Sequence elements critical for efficient RNA editing of a tobacco chloroplast
      transcript in vivo and in vitro.
AB  - In tobacco chloroplast transcripts 34 nt are efficiently edited to U. No common
      consensus region is present around all editing sites; however, sites can be
      grouped in clusters that share short common sequences. Transgene transcripts
      carrying either the wild-type -31/+22 or -31/+60 sequence near NTrpoB C473, an
      editing site within tobacco rpoB transcripts, or three different mutated
      sequences, were all highly edited in vivo. Endogenous transcripts of rpoB, psbL
      and rps14, all of which contain common sequences S1, S2 and S3 5' to NTrpoB C473,
      NTpsbL C2 and NTrps14 C80, were less edited in transgenic plants that over
      express transcripts from NTrpoB C473 transgenes. Extent of reduction of
      endogenous editing differed between transgenic lines expressing mutated -31/+22
      regions, depending on the abundance of the transgene transcripts. The -20/-5
      sequence contains critical 5' sequence elements. Synthetic RNA templates with
      alterations within this 5' region were less efficiently edited in vitro than wild
      type templates, by either tobacco or maize chloroplast extracts. The tobacco
      chloroplast extract supports both RNA editing and processing of 3' transcript
      termini. We conclude that within the -20/-5 region, sequences common to editing
      sites in the transcripts of rpoB, psbL and rps14 are critical for efficient
      NTrpoB C473 editing.

PMID- 16893958
TI  - An RNA aptamer that interferes with the DNA binding of the HSF transcription
      activator.
AB  - Heat shock factor (HSF) is a conserved and highly potent transcription activator.
      It is involved in a wide variety of important biological processes including the
      stress response and specific steps in normal development. Reagents that interfere
      with HSF function would be useful for both basic studies and practical
      applications. We selected an RNA aptamer that binds to HSF with high specificity.
      Deletion analysis defined the minimal binding motif of this aptamer to be two
      stems and one stem-loop joined by a three-way junction. This RNA aptamer
      interferes with normal interaction of HSF with its DNA element, which is a key
      regulatory step for HSF function. The DNA-binding domain plus a flanking linker
      region on the HSF (DL) is essential for the RNA binding. Additionally, this
      aptamer inhibits HSF-induced transcription in vitro in the complex milieu of a
      whole cell extract. In contrast to the previously characterized NF-kappaB
      aptamer, the HSF aptamer does not simply mimic DNA binding, but rather binds to
      HSF in a manner distinct from DNA binding to HSF.

PMID- 16893960
TI  - The Pathway Tools cellular overview diagram and Omics Viewer.
AB  - The Pathway Tools cellular overview diagram is a visual representation of the
      biochemical network of an organism. The overview is automatically created from a
      Pathway/Genome Database describing that organism. The cellular overview includes
      metabolic, transport and signaling pathways, and other membrane and periplasmic
      proteins. Pathway Tools supports interrogation and exploration of cellular
      biochemical networks through the overview diagram. Furthermore, a software
      component called the Omics Viewer provides visual analysis of whole-organism
      datasets using the overview diagram as an organizing framework. For example, gene
      expression and metabolomics measurements, alone or in combination, can be painted
      onto the overview, as can computed whole-organism datasets, such as predicted
      reaction-flux values. The cellular overview and Omics Viewer provide a mechanism
      whereby biologists can apply the pattern-recognition capabilities of the human
      visual system to analyze large-scale datasets in a biologically meaningful
      context. SRI's BioCyc.org website provides overview diagrams for more than 200
      organisms. This article describes enhancements to the overview made since a 1999
      publication, including the automatic layout capability, expansion of the cellular
      machinery that it includes, new semantic zooming and poster-generating
      capabilities, and extension of the Omics Viewer to support painting of
      metabolites, animations and zooming to individual pathway diagrams.

PMID- 16893959
TI  - Sequence-dependent enhancement of hydrolytic deamination of cytosines in DNA by
      the restriction enzyme PspGI.
AB  - Hydrolytic deamination of cytosines in DNA creates uracil and, if unrepaired,
      these lesions result in C to T mutations. We have suggested previously that a
      possible way in which cells may prevent or reduce this chemical reaction is
      through the binding of proteins to DNA. We use a genetic reversion assay to show
      that a restriction enzyme, PspGI, protects cytosines within its cognate site, 5'
      CCWGG (W is A or T), against deamination under conditions where no DNA cleavage
      can occur. It decreases the rate of cytosine deamination to uracil by 7-fold.
      However, the same protein dramatically increases the rate of deaminations within
      the site 5'-CCSGG (S is C or G) by approximately 15-fold. Furthermore, a similar
      increase in cytosine deaminations is also seen with a catalytically inactive
      mutant of the enzyme showing that endonucleolytic ability of the protein is
      dispensable for its mutagenic action. The sequences of the mutants generated in
      the presence of PspGI show that only one of the cytosines in CCSGG is
      predominantly converted to thymine. Our results are consistent with PspGI
      'sensitizing' the cytosine in the central base pair in CCSGG for deamination.
      Remarkably, PspGI sensitizes this base for damage despite its inability to form
      stable complexes at CCSGG sites. These results can be explained if the enzyme has
      a transient interaction with this sequence during which it flips the central
      cytosine out of the helix. This prediction was validated by modeling the
      structure of PspGI-DNA complex based on the structure of the related enzyme
      Ecl18kI which is known to cause base-flipping.

PMID- 16893961
TI  - A study of male veterans' beliefs toward domestic violence in a batterers
      intervention program.
AB  - Domestic violence in intimate relationships is a ubiquitous social problem. This
      study addresses a gap in the research literature on batterers intervention
      programs with heterosexual male batterers by evaluating whether or not self
      reported attitudes about partner abuse and sexist beliefs could be modified over
      time as a result of participation in a Batterers Intervention Program (BIP).
      Using the Inventory of Beliefs about Partner Abuse (IBAPA) to measure attitudes
      toward domestic violence and the Ambivalent Sexism Inventory (ASI) to measure
      sexist beliefs, results of the study provide empirical support for the notion
      that participation in BIPs affects the self-reported beliefs about their rights
      to physically and emotionally abuse their partner. These self-reported scores
      were adjusted for response bias by the long version of the Marlowe-Crowne Social
      Desirability Scale (MCD). Response bias and how it is treated in self-report
      measures with batterers is also discussed.

PMID- 16893962
TI  - Public's and police officers' interpretation and handling of domestic violence
      cases: divergent realities.
AB  - The public's and police officers'interpretation and handling of realistic
      hypothetical domestic violence cases and their stereotypic views about domestic
      violence are discussed. A sample of 131 experienced officers, 127 novice
      officers, and 157 adult laypersons were randomly assigned to read a domestic
      violence case. Experienced officers were more likely to arrest only the husband
      than were laypersons or rookie officers even when respondents inferred that the
      husband was primarily responsible or had used violence before. Experienced
      officers considered their stereotypic beliefs about battered women's propensity
      to use self-defense in arriving at their arrest decision whereas laypersons and
      rookie officers did not. These findings indicate that the public and police
      officers have not adopted the feminists' message that arrest is the best response
      to handle all domestic violence cases. Policy implications are discussed.

PMID- 16893963
TI  - Women's response to intimate partner violence.
AB  - The responses of women to a situation of abuse by their partner has hardly been
      addressed in the literature. Using a self-administered, anonymous questionnaire,
      400 women attending three practices in a primary health care center in Granada
      (Spain) were studied. The women's response to abuse was used as a dependent
      variable. Sociodemographics, intensity, duration, and combination of the types of
      abuse were used as independent variables. Lifetime prevalence of any type of
      partner abuse was 22.8%. Of abused women, 68% showed an active response,
      attempting to resolve the situation mainly through separation (58.2%). The
      factors independently associated with a woman's active response were being
      separated, widowed, or divorced; reporting a greater intensity of abuse; and
      being younger than age 35 years. The results of this study show that a large
      majority of abused women in Spain try to resolve their situation, and that they
      are not passive victims.

PMID- 16893964
TI  - Risk factors for peer sexual harassment in schools.
AB  - This study introduces potential risk factors for victimization and perpetration
      of sexual harassment among teens not previously studied. The first set of
      analyses compared histories of perpetration and victimization by gender, as well
      as the relationship between risk factors and perpetration or victimization. For
      girls (r = .544) and boys (r = .700), the relationships between perpetration and
      victimization histories were very strong. Most proposed risk factors were also
      significantly related to perpetration and victimization histories for both
      genders, including alcohol use frequency, delinquency, histories of family
      violence and victimization, cultural and personal power, and retaliation, with
      all increasing as perpetration or victimization history increased. For girls, two
      direct paths were moderately related to victimization--delinquency and family
      victimization. For boys, only one variable--perpetration history--was related to
      victimization history. Four variables were directly related to greater sexual
      harassment perpetration-greater personal power, delinquency, family violence, and
      family victimization.

PMID- 16893965
TI  - "If it hurts you, then it is not a joke": adolescents' ideas about girls' and
      boys' use and experience of abusive behavior in dating relationships.
AB  - This study examined adolescents' ideas about girls' and boys' use and experience
      of physical and psychological abuse in heterosexual dating relationships.
      Canadian high school students who were enrolled in Grades 9 and 11 took part in
      single-gender focus groups. Eight themes emerged from the analysis. The themes
      highlight the importance teenagers place on context for defining specific
      behaviors as abusive. They also underscore gender differences in the criteria
      adolescents use to make these judgments, in the forms of abusive behavior
      teenagers typically use in a dating relationship, and in the reasons for youths'
      declining use of physical abuse and increasing use of psychological abuse. These
      views have important implications for future research and for programs targeting
      adolescent dating violence.

PMID- 16893966
TI  - Rape-myth congruent beliefs in women resulting from exposure to violent
      pornography: effects of alcohol and sexual arousal.
AB  - Previous research findings indicate that women suffer a variety of detrimental
      effects from exposure to violent pornography. This study used an experimental
      paradigm to examine the effects of a moderate alcohol dose and alcohol
      expectancies on women's acute reactions to a violent pornographic stimulus. A
      community sample of female social drinkers (N = 134) read an eroticized rape
      depiction after completing an alcohol administration protocol. As predicted,
      intoxicated participants were less likely to label the depicted events as rape
      than their sober counterparts. A path analytic model illustrated that
      participants' self-reported sexual arousal to the stimulus, as influenced by
      alcohol consumption and expectancies, resulted in increased rape myth congruent
      perceptions of the victim and decreased labeling of the incident as rape.
      Findings suggest that acute alcohol intoxication during violent pornography
      exposure may ultimately result in women developing more calloused attitudes
      toward rape and rape victims.

PMID- 16893967
TI  - Repetition or reparation? An exploratory study of the relationship schemas of
      child molesters in treatment.
AB  - This exploratory study examined the relationship patterns of child abusers in
      treatment by comparing interactions involving the therapist with those involving
      a parent. Twenty participants were included in the study. The participants'
      relationship patterns were assessed using the core conflictual relationship theme
      (CCRT) method. Core schemas were found in interactions involving the therapist
      and a parent. The two CCRTs found in interactions with parents were often
      motivated by a desire for closeness or intimacy, to which the parent reacted with
      rejection or domination. The participants then felt disappointed, depressed, and
      unreceptive. In relationship episodes involving the therapist, a similar desire
      for closeness was answered with help and cooperation from the therapist, hence
      leading the participants to feel self-controlled and self-confident. Furthermore,
      the therapist's criticism and opposition was often experienced as an indication
      of care and acceptance.

PMID- 16893968
TI  - The relationship between trauma and violence in a jail inmate sample.
AB  - Research suggests there is a link between trauma and violence, although the
      nature of the relationship is rather equivocal. This study explored this
      relationship by examining self-reported trauma as a predictor of self-reported
      violence in 93 jail inmates. Ninety-six percent of the sample reported
      experiencing a traumatic event, and 67% reported having been violent during the
      year preceding incarceration. Inmates reporting trauma were more than twice as
      likely to report having been violent than nonviolent. Stepwise multiple
      regression analyses suggested traumatic events, as a combined model,
      significantly contributed to violence perpetration. In addition, witnessing
      serious violence predicted perpetration of violence. Implications and limitations
      of the present study are discussed.

PMID- 16893969
TI  - The novel gene asb11: a regulator of the size of the neural progenitor
      compartment.
AB  - From a differential display designed to isolate genes that are down-regulated
      upon differentiation of the central nervous system in Danio rerio embryos, we
      isolated d-asb11 (ankyrin repeat and suppressor of cytokine signaling box
      containing protein 11). Knockdown of the d-Asb11 protein altered the expression
      of neural precursor genes sox2 and sox3 and resulted in an initial relative
      increase in proneural cell numbers. This was reflected by neurogenin1 expansion
      followed by premature neuronal differentiation, as demonstrated by HuC labeling
      and resulting in reduced size of the definitive neuronal compartment. Forced
      misexpression of d-asb11 was capable of ectopically inducing sox2 while it
      diminished or entirely abolished neurogenesis. Overexpression of d-Asb11 in both
      a pluripotent and a neural-committed progenitor cell line resulted in the
      stimulus-induced inhibition of terminal neuronal differentiation and enhanced
      proliferation. We conclude that d-Asb11 is a novel regulator of the neuronal
      progenitor compartment size by maintaining the neural precursors in the
      proliferating undifferentiated state possibly through the control of SoxB1
      transcription factors.

PMID- 16893970
TI  - Vascular endothelial cadherin controls VEGFR-2 internalization and signaling from
      intracellular compartments.
AB  - Receptor endocytosis is a fundamental step in controlling the magnitude,
      duration, and nature of cell signaling events. Confluent endothelial cells are
      contact inhibited in their growth and respond poorly to the proliferative signals
      of vascular endothelial growth factor (VEGF). In a previous study, we found that
      the association of vascular endothelial cadherin (VEC) with VEGF receptor (VEGFR)
      type 2 contributes to density-dependent growth inhibition (Lampugnani, G.M., A.
      Zanetti, M. Corada, T. Takahashi, G. Balconi, F. Breviario, F. Orsenigo, A.
      Cattelino, R. Kemler, T.O. Daniel, and E. Dejana. 2003. J. Cell Biol. 161:793
      804). In the present study, we describe the mechanism through which VEC reduces
      VEGFR-2 signaling. We found that VEGF induces the clathrin-dependent
      internalization of VEGFR-2. When VEC is absent or not engaged at junctions, VEGFR
      2 is internalized more rapidly and remains in endosomal compartments for a longer
      time. Internalization does not terminate its signaling; instead, the internalized
      receptor is phosphorylated, codistributes with active phospholipase C-gamma, and
      activates p44/42 mitogen-activated protein kinase phosphorylation and cell
      proliferation. Inhibition of VEGFR-2 internalization reestablishes the contact
      inhibition of cell growth, whereas silencing the junction-associated density
      enhanced phosphatase-1/CD148 phosphatase restores VEGFR-2 internalization and
      signaling. Thus, VEC limits cell proliferation by retaining VEGFR-2 at the
      membrane and preventing its internalization into signaling compartments.

PMID- 16893971
TI  - PKCalpha: a versatile key for decoding the cellular calcium toolkit.
AB  - Conventional protein kinases C (cPKCs) play an essential role in signal
      transduction and are believed to integrate both global Ca(2+) transients and
      diacylglycerol signals. We provide evidence that PKCalpha is a ubiquitous readout
      sensor for the cellular Ca(2+) toolkit, including highly restricted elementary
      Ca(2+) release. Threshold stimulations of cells with Ca(2+)-mobilizing agonists
      resulted in PKCalpha translocation events with limited spatial spreads (<4
      microm) comprising two groups of lifetimes; brief events (400-1,500 ms)
      exclusively mediated by Ca(2+)-C2 domain membrane interactions and long-lasting
      events (>4 s) resulting from longer DAG-C1a domain-mediated membrane
      interactions. Although upon uncaging NP-EGTA, which is a caged Ca(2+) compound,
      WT-PKCalpha displayed rapid membrane translocations within <250 ms, PKCalpha
      constructs with C2 domains mutated in their Ca(2+)-binding region lacked any
      Ca(2+)-dependent translocation. Flash photolysis of diazo-2, a photosensitive
      caged Ca(2+) buffer, revealed a biphasic membrane dissociation (slow and fast
      period) of WT-PKCalpha. The slow phase was absent in cells expressing PKCalpha
      constructs containing mutated C1a-domains with largely reduced DAG binding. Thus,
      two groups of PKCalpha membrane interactions coexist; C2- and C1a-mediated
      interactions with different lifetimes but rapid interconversion. We conclude that
      PKCalpha can readout very fast and, spatially and temporally, very complex
      cellular Ca(2+) signals. Therefore, cPKCs are important transducers for the
      ubiquitous cellular Ca(2+) signaling toolkit.

PMID- 16893972
TI  - The mitochondrial protein Bak is pivotal for gliotoxin-induced apoptosis and a
      critical host factor of Aspergillus fumigatus virulence in mice.
AB  - Aspergillus fumigatus infections cause high levels of morbidity and mortality in
      immunocompromised patients. Gliotoxin (GT), a secondary metabolite, is cytotoxic
      for mammalian cells, but the molecular basis and biological relevance of this
      toxicity remain speculative. We show that GT induces apoptotic cell death by
      activating the proapoptotic Bcl-2 family member Bak, but not Bax, to elicit the
      generation of reactive oxygen species, the mitochondrial release of apoptogenic
      factors, and caspase-3 activation. Activation of Bak by GT is direct, as GT
      triggers in vitro a dose-dependent release of cytochrome c from purified
      mitochondria isolated from wild-type and Bax- but not Bak-deficient cells.
      Resistance to A. fumigatus of mice lacking Bak compared to wild-type mice
      demonstrates the in vivo relevance of this GT-induced apoptotic pathway involving
      Bak and suggests a correlation between GT production and virulence. The
      elucidation of the molecular basis opens new strategies for the development of
      therapeutic regimens to combat A. fumigatus and related fungal infections.

PMID- 16893973
TI  - Meiotic cohesins modulate chromosome compaction during meiotic prophase in
      fission yeast.
AB  - The meiotic cohesin Rec8 is required for the stepwise segregation of chromosomes
      during the two rounds of meiotic division. By directly measuring chromosome
      compaction in living cells of the fission yeast Schizosaccharomyces pombe, we
      found an additional role for the meiotic cohesin in the compaction of chromosomes
      during meiotic prophase. In the absence of Rec8, chromosomes were decompacted
      relative to those of wild-type cells. Conversely, loss of the cohesin-associated
      protein Pds5 resulted in hypercompaction. Although this hypercompaction requires
      Rec8, binding of Rec8 to chromatin was reduced in the absence of Pds5, indicating
      that Pds5 promotes chromosome association of Rec8. To explain these observations,
      we propose that meiotic prophase chromosomes are organized as chromatin loops
      emanating from a Rec8-containing axis: the absence of Rec8 disrupts the axis,
      resulting in disorganized chromosomes, whereas reduced Rec8 loading results in a
      longitudinally compacted axis with fewer attachment points and longer chromatin
      loops.

PMID- 16893974
TI  - Unique and redundant functional domains of APETALA1 and CAULIFLOWER, two recently
      duplicated Arabidopsis thaliana floral MADS-box genes.
AB  - APETALA1 (AP1) and CAULIFLOWER (CAL) are closely related MADS box genes that are
      partially redundant during Arabidopsis thaliana floral meristem determination.
      AP1 is able to fully substitute for CAL functions, but not vice versa, and AP1
      has unique sepal and petal identity specification functions. In this study, the
      unique and redundant functions of these two genes has been mapped to the four
      protein domains that characterize type-II MADS-domain proteins by expressing all
      15 chimeric combinations of AP1 and CAL cDNA regions under control of the AP1
      promoter in ap1-1 loss-of-function plants. The "in vivo" function of these
      chimeric genes was analysed in Arabidopsis plants by expressing the chimeras.
      Rescue of flower meristem and sepal/petal identities was scored in single and
      multiple insert homozygous transgenic lines. Using these chimeric lines, it was
      found that distinct residues of the AP1 K domain not shared by the same CAL
      domain are necessary and sufficient for complete recovery of floral meristem
      identity, in the context of the CAL protein sequence, while both AP1 COOH and K
      domains are indispensable for complete rescue of sepal identity. By contrast,
      either one of these two AP1 domains is necessary and sufficient for complete
      petal identity recovery. It was also found that there were positive and negative
      synergies among protein domains and their combinations, and that multiple-insert
      lines showed relatively better rescue than equivalent single-insert lines.
      Finally, several lines had flowers with extra sepals and petals suggesting that
      chimeric proteins yield abnormal transcriptional complexes that may alter the
      expression or regulation of genes that control floral organ number under normal
      conditions.

PMID- 16893975
TI  - Identifying cytoplasmic input to the cell wall of growing Chara corallina.
AB  - Plants enlarge mostly because the walls of certain cells enlarge, with
      accompanying input of wall constituents and other factors from the cytoplasm.
      However, the enlargement can occur without input, suggesting an uncertain
      relationship between cytoplasmic input and plant growth. Therefore, the role of
      the input was investigated by quantitatively comparing growth in isolated walls
      (no input) with that in living cells (input occurring). Cell walls were isolated
      from growing internodes of Chara corallina and filled with pressurized oil to
      control turgor pressure while elongation was monitored. Turgor pressure in living
      cells was similarly controlled and monitored by adding/removing cell solution.
      Temperature was varied in some experiments. At all pressures and temperatures,
      isolated walls displayed turgor-driven growth indistinguishable in every respect
      from that in living cells, except the rate decelerated in the isolated walls
      while the living cells grew rapidly. The growth in the isolated walls was highly
      responsive to temperature, in contrast to the elastic extension that has been
      shown to be insensitive to similar temperatures. Consequently, strong
      intermolecular bonds were responsible for growth and weak bonds for elastic
      extension. Boiling the walls gave the same results, indicating that enzyme
      activities were not controlling these bonds. However, pectin added to isolated
      walls reversed their growth deceleration and returned the rate to that in the
      living cells. The pectin was similar to that normally produced by the cytoplasm
      and deposited in the wall, suggesting that continued cytoplasmic input of pectin
      may play a role in sustaining turgor-driven growth in Chara.

PMID- 16893976
TI  - The face value of ion fluxes: the challenge of determining influx in the low
      affinity transport range.
AB  - The existence of distinct high- and low-affinity transport systems (HATS and
      LATS) is well established for major nutrient ions. However, influx mediated by
      these systems is usually estimated using uniformly simple tracer protocols. Two
      (42)K radiotracer methods to measure potassium influxes in the HATS and LATS
      ranges in intact barley (Hordeum vulgare L.) roots are compared here: a direct
      influx (DI) method, and an integrated flux analysis (IFA), which is designed to
      account for tracer efflux from labelled roots and differential tracer
      accumulation along the plant axis. Methods showed only minor discrepancies for
      influx values in the HATS range, but large discrepancies in the LATS range,
      revealing striking distinctions in the cellular exchange properties dominated by
      the operation of the two transport systems. It is shown that accepted DI
      protocols are associated with very large errors in the high-conductance LATS
      range, underestimating influx at least 6-fold due to four characteristics of this
      transport mode: (i) accelerated cellular (42)K exchange; (ii) a greatly increased
      ratio of efflux to influx; (iii) increased (42)K loss during the removal of water
      from roots in preweighing centrifugation or blotting protocols; and (iv)
      increased (42)K retention at the root-shoot interface, a region of the plant
      frequently disregarded in DI determinations. The findings warrant a re-evaluation
      of a large body of literature reporting influx in the LATS range, and are of
      fundamental importance to ion flux experimentation in plant physiology.

PMID- 16893977
TI  - The presence of jasmonate-inducible lectin genes in some but not all Nicotiana
      species explains a marked intragenus difference in plant responses to hormone
      treatment.
AB  - Tobacco (Nicotiana tabacum L. cv Samsun NN) leaves accumulate a
      cytoplasmic/nuclear lectin, called Nictaba, in response to methyl jasmonate. To
      check whether, and if so to what extent, the specific induction of this lectin
      applies to related species, a collection of 19 Nicotiana species--covering 12
      Nicotiana sections and eight Nicotiana tabacum cultivars--was screened for their
      capability to synthesize the jasmonate-inducible lectin. Protein analyses by
      agglutination assays and western blot confirmed that only nine out of the 19
      species examined synthesize lectin after jasmonate treatment. Remarkably, all
      allotetraploid cultivars of the N. tabacum L. species tested express the lectin
      after jasmonate treatment. PCR analyses demonstrated that all responsive species
      possess one or more lectin genes, whereas no lectin gene(s) could be traced in
      the non-responding species. The number of introns present in the lectin genes
      varies between zero and two. Four tobacco species/cultivars contain both
      intronless Nictaba genes as well as lectin genes with introns. These findings
      provide the first firm evidence for a striking intragenus difference with respect
      to the activation of a well-defined jasmonate-inducible gene that can be
      correlated with the presence/absence of orthologous genes in the genomes of
      closely related species from a single plant genus. In addition, the differential
      response of closely related tobacco species illustrates that in the field of
      plant hormone research, care must be taken when extrapolating results obtained
      with a particular model system to other--even taxonomically closely related-
      species.

PMID- 16893978
TI  - Nitric oxide (NO) detection by DAF fluorescence and chemiluminescence: a
      comparison using abiotic and biotic NO sources.
AB  - Because of controversies in the literature on nitric oxide (NO) production by
      plants, NO detection by the frequently used diaminofluorescein (DAF-2 and DAF
      2DA) and by chemiluminescence were compared using the following systems of
      increasing complexity: (i) dissolved NO gas; (ii) the NO donor sodium
      nitroprusside (SNP); (iii) purified nitrate reductase (NR); and (iv) tobacco cell
      suspensions. Low (physiological) concentrations (< or =1 nM) of dissolved NO
      could be precisely quantified by chemiluminescence, but caused no DAF-2
      fluorescence. In contrast to NO gas, SNP, NR, or cell suspensions produced both
      good DAF fluorescence and chemiluminescence signals which were completely
      (chemiluminescence) or partly (DAF fluorescence) prevented by NO scavengers.
      Signal strength ratios between the two methods were variable depending on the NO
      source, and eventually reflect variable NO oxidation. DAF fluorescence in cell
      suspension cultures was also increased by an as yet unidentified compound(s)
      released from cells into the medium. These compounds gave no chemiluminescence
      signal and were not produced by NR-free mutants. Their production was stimulated
      by anoxia, by inhibitors of mitochondrial electron transport, and by the fungal
      elicitor cryptogein. Thus, changes in DAF fluorescence are not necessarily
      indicative for NO production, but may also reflect NO oxidation and/or production
      of other DAF-reactive compounds.

PMID- 16893979
TI  - Thermal energy dissipation in reaction centres and in the antenna of photosystem
      II protects desiccated poikilohydric mosses against photo-oxidation.
AB  - Seasonal differences have been observed in the ability of desiccated mosses to
      dissipate absorbed light energy harmlessly into heat. During the dry summer
      season desiccation-tolerant mosses were more protected against photo-oxidative
      damage in the dry state than during the more humid winter season. Investigation
      of the differences revealed that phototolerance could be acquired or lost even
      under laboratory conditions. When a desiccated poikilohydric moss such as
      Rhytidiadelphus squarrosus is in the photosensitive state, the primary quinone,
      Q(A), in the reaction centre of photosystem II is readily reduced even by low
      intensity illumination as indicated by reversibly increased chlorophyll
      fluorescence. No such reduction is observed even under strong illumination in
      desiccated mosses after phototolerance has been acquired. In this state,
      reductive charge stabilization is replaced by energy dissipation. As a
      consequence, chlorophyll fluorescence is quenched. Different mechanisms are
      responsible for quenching. One is based on the presence of zeaxanthin provided
      drying occurs in the light. This mechanism is known to be controlled by a
      protonation reaction which is based on proton-coupled electron transport while
      the moss is still hydrated. Another mechanism which also requires light for
      activation, but no protonation, is activated during desiccation. While water is
      slowly lost, fluorescence is quenched. In this situation, an absorption band
      formed at 800 nm in the light is stabilized. It loses reversibility on darkening.
      Comparable kinetics of fluorescence quenching and 800 nm signals as well as the
      linear relationship between non-photochemical fluorescence quenching (NPQ) and
      loss of stable charge separation in photosystem II reaction centres suggested
      that desiccation-induced quenching is a property of photosystem II reaction
      centres. During desiccation, quenchers accumulate which are stable in the absence
      of water but revert to non-quenching molecular species on hydration. Together
      with zeaxanthin-dependent energy dissipation, desiccation-induced thermal energy
      dissipation protects desiccated poikilohydric mosses against photo-oxidation,
      ensuring survival during drought periods.

PMID- 16893980
TI  - Vaccines: all things considered.

PMID- 16893981
TI  - Cloning, characterization, and expression of Bartonella henselae p26.
AB  - In order to identify immunoreactive Bartonella henselae proteins, B. henselae
      antiserum from an experimentally infected cat was used to screen a B. henselae
      genomic DNA expression library. One immunoreactive phage clone contained a gene
      (p26) with significant nucleotide identity with orthologs in brucellae,
      bartonellae, and several plant-associated bacteria. p26 gene sequences from four
      B. henselae strains, one B. koehlerae strain, and one B. clarridgeiae strain were
      cloned. Comparative nucleotide sequence analysis showed that p26 is a potential
      marker for molecular diagnosis of infection, as well as for identification to
      species level and genotyping of Bartonella sp. isolates. Alignment of the
      predicted amino acid sequences illustrated conserved putative protein features
      including a hydrophobic transmembrane region, a peptide cleavage site, and four
      dominant antigenic sites. Expression of p26 in Escherichia coli produced two
      proteins (26 and 27.5 kDa), both of which were reactive with feline anti-B.
      henselae antisera. Furthermore, murine hyperimmune serum raised against either
      recombinant protein reacted with both proteins. No reactivity to either
      recombinant protein was detected in nonimmune serum, and reactivity persisted as
      long as 20 weeks for one cat. The p26 protein product is an immunodominant
      antigen that is expressed during infection in cats as a preprotein and is
      subsequently cleaved to form mature P26.

PMID- 16893982
TI  - A highly sensitive and subspecies-specific surface antigen enzyme- linked
      immunosorbent assay for diagnosis of Johne's disease.
AB  - Johne's disease (JD), or paratuberculosis, caused by Mycobacterium avium subsp.
      paratuberculosis, is one of the most widespread and economically important
      diseases of livestock and wild ruminants worldwide. Control of JD could be
      accomplished by diagnosis and good animal husbandry, but this is currently not
      feasible because commercially available diagnostic tests have low sensitivity
      levels and are incapable of diagnosing prepatent infections. In this study, a
      highly sensitive and subspecies-specific enzyme-linked immunosorbent assay was
      developed for the diagnosis of JD by using antigens extracted from the surface of
      M. avium subsp. paratuberculosis. Nine different chemicals and various intervals
      of agitation by vortex were evaluated for their ability to extract the surface
      antigens. Various quantities of surface antigens per well in a 96-well microtiter
      plate were also tested. The greatest differences in distinguishing between JD
      positive and JD-negative serum samples by ethanol vortex enzyme-linked
      immunosorbent assay (EVELISA) were obtained with surface antigens dislodged from
      50 microg/well of bacilli treated with 80% ethanol followed by a 30-second
      interval of agitation by vortex. The diagnostic specificity and sensitivity of
      the EVELISA were 97.4% and 100%, respectively. EVELISA plates that had been
      vacuum-sealed and then tested 7 weeks later (the longest interval tested) had
      diagnostic specificity and sensitivity rates of 96.9 and 100%, respectively. In a
      comparative study involving serum samples from 64 fecal culture-positive cattle,
      the EVELISA identified 96.6% of the low-level fecal shedders and 100% of the
      midlevel and high-level shedders, whereas the Biocor ELISA detected 13.7% of the
      low-level shedders, 25% of the mid-level shedders, and 96.2% of the high-level
      shedders. Thus, the EVELISA was substantially superior to the Biocor ELISA,
      especially in detecting low-level and midlevel shedders. The EVELISA may form the
      basis for a highly sensitive and subspecies-specific test for the diagnosis of
      JD.

PMID- 16893983
TI  - Plant-produced cottontail rabbit papillomavirus L1 protein protects against tumor
      challenge: a proof-of-concept study.
AB  - The native cottontail rabbit papillomavirus (CRPV) L1 capsid protein gene was
      expressed transgenically via Agrobacterium tumefaciens transformation and
      transiently via a tobacco mosaic virus (TMV) vector in Nicotiana spp. L1 protein
      was detected in concentrated plant extracts at concentrations up to 1.0 mg/kg in
      transgenic plants and up to 0.4 mg/kg in TMV-infected plants. The protein did not
      detectably assemble into viruslike particles; however, immunoelectron microscopy
      showed presumptive pentamer aggregates, and extracted protein reacted with
      conformation-specific and neutralizing monoclonal antibodies. Rabbits were
      injected with concentrated protein extract with Freund's incomplete adjuvant. All
      sera reacted with baculovirus-produced CRPV L1; however, they did not detectably
      neutralize infectivity in an in vitro assay. Vaccinated rabbits were, however,
      protected against wart development on subsequent challenge with live virus. This
      is the first evidence that a plant-derived papillomavirus vaccine is protective
      in an animal model and is a proof of concept for human papillomavirus vaccines
      produced in plants.

PMID- 16893984
TI  - Early appearance of bactericidal antibodies after polysaccharide challenge of
      toddlers primed with a group C meningococcal conjugate vaccine: what is its role
      in the maintenance of protection?
AB  - The contribution of memory responses after meningococcal vaccination to
      protection may depend on the rapidity of the response. Toddlers were challenged
      with a licensed polysaccharide (PS) vaccine 1 year after vaccination with a
      single dose of meningococcal group C-CRM(197) conjugate (MCC) vaccine at the age
      of 12 to 15 months. Bactericidal antibodies and immunoglobulin G (IgG) antibodies
      detected by an enzyme-linked immunosorbent assay (ELISA) were measured before
      challenge and 4, 7, 14, or 21 Days later ("Days" refer to treatment groups,
      "days" to sampling days). Among 281 subjects in the intent-to-treat population,
      173 per-protocol (PP) subjects were challenged with 10 microg PS antigen and 103
      others with a 50-microg PS vaccinating dose. Capsular PS-specific ELISA IgG
      titers were negligible in baseline samples and increased only twofold within 4
      days of PS administration. In contrast, the proportion of PP subjects with serum
      bactericidal antibody (SBA) titers of >or=1:8 or >or=1:128 increased,
      respectively, from 41% and 16% before challenge to 84% and 74% at Day 4 and to
      100% and 97% at Day 7. Recipients of 50 microg PS responded with similar kinetics
      but showed a trend toward higher antibody levels. Unexpectedly, 69% of subjects
      bled on days 2 to 3 already had achieved SBA titers of >or=1:8. The majority of
      toddlers previously immunized with MCC and challenged 1 year later with PS
      antigen mounted protective levels of bactericidal antibody within 2 to 4 days.

PMID- 16893985
TI  - Quantitative analysis of levels of serum immunoglobulin G against botulinum
      neurotoxin type D and association with protection in natural outbreaks of cattle
      botulism.
AB  - The recent outbreaks of cattle botulism in vaccinated Israeli dairy cattle
      prompted us to determine vaccine efficacy and reasons for vaccine failure.
      Analysis of clinical signs, feeding practice, vaccination history, and epidemic
      curves enabled us to define a study population in two outbreaks, where high doses
      of Clostridium botulinum neurotoxin type D (BoNT/D) were evenly consumed by the
      affected animal groups. Attack rates among unvaccinated 6- to 24-month-old
      heifers were 96% (55/57) and 85% (53/62). The attack rates in vaccinated parity
      1, 2, and >or=3 cows were 40.4% (21/52), 14.3% (4/28), and 5.6% (3/54),
      respectively. Vaccine efficacies for these cow groups were 52.5%, 83.2%, and
      93.4%, respectively. In younger, unvaccinated 2- to 6-month-old calves,
      presumably protected by maternal antibodies, the attack rate was 24% (17/71).
      These differences correlated with significant differences in levels of specific
      anti-BoNT/D antibody in serum by an enzyme-linked immunosorbent assay (ELISA).
      The ELISA performance for predicting protection was analyzed by receiver
      operating characteristic analysis and was found to be highly significant, with an
      area under the curve of 0.941 (standard error, 0.034; 95% confidence interval,
      0.875 to 1.008; P < 0.000). No animals with serum ELISA unit levels above 0.33
      were affected in these exposed groups. At this cutoff level, the specificity of
      the ELISA was 100%, sensitivity was 67%, and accuracy was 92%. We concluded that
      botulinum toxoids can confer adequate protection against natural exposure to
      lethal doses of BoNT/D; however, the vaccination protocols should be optimized.
      Our in-house ELISA system will enable us to optimize vaccination protocols in the
      animal population.

PMID- 16893986
TI  - Mycobacterium tuberculosis HBHA protein reacts strongly with the serum
      immunoglobulin M of tuberculosis patients.
AB  - Identification and characterization of serologically active mycobacterial
      antigens are prerequisites for the development of diagnostic reagents. We
      examined the humoral immune responses of active tuberculosis (TB) patients
      against Triton-soluble proteins extracted from Mycobacterium tuberculosis by
      immunoblotting. A 29-kDa protein reacted with immunoglobulin M (IgM) in the
      pooled sera of the patients, and its N-terminal amino acid sequence matched that
      of the heparin-binding hemagglutinin (HBHA). Recombinant full-length HBHA was
      expressed in Escherichia coli (rEC-HBHA) and M. smegmatis (rMS-HBHA). In
      immunoblot analysis, the IgM antibodies of the TB patients reacted strongly with
      rMS-HBHA but not with rEC-HBHA, whereas the IgG antibodies of these patients
      reacted weakly with both recombinant HBHA proteins. In enzyme-linked
      immunosorbent assay analysis using rMS-HBHA and 85B as antigens, the mean levels
      and sensitivities of the anti-HBHA IgM antibodies of the TB patients were
      significantly higher than those of the anti-antigen 85B IgM antibodies, while the
      IgG antibodies showed the opposite results. Of interest in this respect, the
      pooled sera from the TB patients that contained anti-HBHA IgM antibodies
      neutralized the entry of M. tuberculosis into epithelial cells. These findings
      suggest that IgM antibody to HBHA may play a role in protection against
      extrapulmonary dissemination.

PMID- 16893987
TI  - Regulation of lipopolysaccharide-induced interleukin-12 production by activation
      of repressor element GA-12 through hyperactivation of the ERK pathway.
AB  - Interleukin-12 (IL-12) functions as a representative lipopolysaccharide (LPS)
      mediator in both innate and adaptive immunity. We investigated the regulation of
      LPS-induced IL-12 production by mouse macrophages. In response to LPS, peritoneal
      macrophages produced bioactive IL-12 p70, a heterodimer (p40/p35) of subunits,
      but macrophage lines such as J774.1 and RAW264.7 did not. Induction of the p35
      subunit was impaired in both cell lines, and additional impairment of p40
      induction was observed in RAW264.7 cells. These results suggest that some
      negative regulatory mechanisms against LPS-induced IL-12 p40 production are
      constitutively functioning in RAW264.7 cells but not in the other types of cells.
      Activation of GA-12 (a repressor element of IL-12 p40), rather than suppression
      of promoter elements, such as binding sites for NF-kappaB, AP-1, and IRF-1, was
      detected in LPS-stimulated RAW264.7 cells, accompanying hyperactivation of
      extracellular signal-related kinase (ERK). When ERK activation was suppressed by
      an inhibitor (U0126), production of p40 rose from an undetectable to a
      substantial level and GA-12 activation decreased. In peritoneal macrophages,
      stimulation with a high dose of LPS reduced p40 production with enhanced
      activation of ERK. Pretreatment of the cells with phorbol myristate acetate to
      enhance ERK activation reduced p40 production in response to the optimal LPS
      stimulation. Taken together, these results demonstrate that hyperactivation of
      the ERK pathway plays a role in upstream signaling for the activation of GA-12,
      leading to the repression of IL-12 p40 production in mouse macrophages.

PMID- 16893989
TI  - Association of CD14 promoter polymorphism with otitis media and pneumococcal
      vaccine responses.
AB  - Innate immunity is of particular importance for protection against infection
      during early life, when adaptive immune responses are immature. CD14 plays key
      roles in innate immunity, including in defense against pathogens associated with
      otitis media, a major pediatric health care issue. The T allele of the CD14 C
      159T polymorphism has been associated with increased serum CD14 levels. Our
      objective was to investigate the hypothesis that the CD14 C-159T allele is
      protective against recurrent acute otitis media in children. The association
      between the CD14 promoter genotype and the number of acute otitis media episodes
      was evaluated both retrospectively and prospectively in a cohort of 300 children.
      Serotype-specific immunoglobulin G (IgG) antibody responses after pneumococcal
      vaccinations were examined according to CD14 genotype to compare immune
      responsiveness across genotypes. An age-dependent association was found: compared
      with that for CC homozygotes aged between 12 to 24 months, TT homozygotes had
      fewer episodes of acute otitis media (79 versus 41%, respectively; P = 0.004);
      this relationship was absent in older children. Additionally, TT homozygotes
      showed higher serotype-specific anti-pneumococcal IgG antibody levels. Our data
      suggest that genetic variation in CD14, a molecule at the interface of innate and
      adaptive immune responses, plays a key role in the defense against middle ear
      disease in childhood and in pneumococcal vaccine responsiveness. These findings
      are likely to be important to these and other immune-mediated outcomes in early
      life.

PMID- 16893988
TI  - Anti-CD25 antibody treatment of mice vaccinated and challenged with Borrelia spp.
      does not exacerbate arthritis but inhibits borreliacidal antibody production.
AB  - CD4(+) CD25(+) T cells are a population of regulatory T cells responsible for the
      modulation of the immune response in several autoimmune and infectious disease
      models. We previously showed that adoptive transfer of enriched CD4(+) CD25(+) T
      cells also plays a major role in the prevention of arthritis in Borrelia
      vaccinated (Borrelia burgdorferi isolate 297) and -challenged (B. bissettii)
      mice. Here, we present evidence that administration of anti-CD25 antibody at the
      time of challenge or at later intervals fails to enhance the development of
      severe destructive osteoarthropathy in Borrelia-vaccinated C57BL mice. However,
      Borrelia-vaccinated and -challenged mice receiving anti-CD25 antibody developed
      decreased borreliacidal antibody titers compared to vaccinated and challenged
      controls. These findings suggest that additional mechanisms besides CD4(+)
      CD25(+) T cells are involved in the regulation of the immune response to Borrelia
      infection following vaccination.

PMID- 16893990
TI  - Influenza virus NS vectors expressing the mycobacterium tuberculosis ESAT-6
      protein induce CD4+ Th1 immune response and protect animals against tuberculosis
      challenge.
AB  - Infection with Mycobacterium tuberculosis remains a major cause of morbidity and
      mortality all over the world. Since the effectiveness of the only available
      tuberculosis vaccine, Mycobacterium bovis bacillus Calmette-Guerin (BCG), is
      suboptimal, there is a strong demand to develop new tuberculosis vaccines. As
      tuberculosis is an airborne disease, the intranasal route of vaccination might be
      preferable. Live influenza virus vaccines might be considered as potential
      vectors for mucosal immunization against various viral or bacterial pathogens,
      including M. tuberculosis. We generated several subtypes of attenuated
      recombinant influenza A viruses expressing the 6-kDa early secretory antigenic
      target protein (ESAT-6) of M. tuberculosis from the NS1 reading frame. We were
      able to demonstrate the potency of influenza virus NS vectors to induce an M.
      tuberculosis-specific Th1 immune response in mice. Moreover, intranasal
      immunization of mice and guinea pigs with such vectors induced protection against
      mycobacterial challenge, similar to that induced by BCG vaccination.

PMID- 16893991
TI  - Enzyme-linked immunosorbent assay for measuring antibodies to pneumococcal
      polysaccharides for the PNEUMOVAX 23 vaccine: assay operating characteristics and
      correlation to the WHO international assay.
AB  - The Merck pneumococcal (Pn) enzyme-linked immunosorbent assays (ELISAs) for
      measuring antibodies to 12 serotypes (serotypes 1, 3, 4, 6B, 7F, 8, 9V, 12F, 14,
      18C, 19F, and 23F) were validated in 1999. Merck Laboratories developed the Pn
      assays using 10 microg/ml C polysaccharide, 100 microg/ml Pn polysaccharide
      (PnPs) 25, and 100 microg/ml PnPs 72 for preadsorption of samples, standards, and
      controls in order to improve the specificity to the Pn serotypes in the vaccine.
      The Pn assays utilize postimmunization sera obtained from subjects immunized with
      PNEUMOVAX 23 as standards for measuring immunoglobulin G concentrations in sera
      obtained from vaccine clinical trials with adults and infants. This material was
      calibrated to the Pn reference standard serum, 89SF, subjected to the Merck Pn
      ELISA adsorbants. Comparisons were made between the Merck Pn assay and the
      international Pn assay, showing moderate agreement between the two assay formats.
      This work describes the test procedures and operating characteristics of the
      Merck Pn assays and the results of experiments performed to compare the Merck Pn
      ELISAs to the international Pn ELISAs.

PMID- 16893993
TI  - Porcine circovirus type 2 infection decreases the efficacy of a modified live
      porcine reproductive and respiratory syndrome virus vaccine.
AB  - Porcine reproductive and respiratory syndrome virus (PRRSV)-induced pneumonia is
      a major problem, and vaccination is used to reduce losses associated with PRRSV.
      Porcine circovirus type 2 (PCV2) causes lymphoid depletion, and there is concern
      that this adversely affects the immune response. The objective of this study was
      to investigate the effect of PCV2 infection on the efficacy of modified live
      virus (MLV) PRRSV vaccine. Sixty-nine 2-week-old pigs were randomly assigned to
      one of seven groups of 9 to 10 pigs each. At 6 weeks of age, pigs in groups 4, 5,
      and 6 were inoculated intranasally with PCV2 ISU-40895. At 8 weeks of age, groups
      3, 4, 6, and 7 were vaccinated with a PRRSV MLV vaccine. At 12 weeks of age,
      groups 2, 3, and 4 were challenged with PRRSV SDSU73. All pigs were necropsied 14
      days after PRRSV challenge. PCV2-infected, PRRSV-vaccinated, and PRRSV-challenged
      pigs had significantly (P < 0.05) more-severe macroscopic lung lesions than did
      the PRRSV-vaccinated and PRRSV-challenged pigs that were not exposed to PCV2
      prior to PRRSV vaccination. Nonvaccinated PRRSV-infected pigs had a significantly
      (P < 0.001) higher incidence of PRRSV antigen in lungs than did all other groups
      except the group infected with PCV2 prior to PRRSV vaccination and challenge. The
      nonvaccinated PRRSV-challenged group and the group challenged with PCV2 prior to
      PRRSV vaccination and challenge had significantly (P < 0.001) lower average daily
      weight gain than did the control and the vaccinated groups. This work suggests
      that PCV2 infection has an adverse effect on the development of protective
      immunity induced by PRRSV vaccine.

PMID- 16893992
TI  - Identification and characterization of immunogenic proteins of mycoplasma
      genitalium.
AB  - Mycoplasma genitalium causes nonchlamydial nongonococcal urethritis. M.
      genitalium was detected by PCR in 17 urethral swabs obtained from 99 men with and
      without urethritis (J. S. Jensen, R. Orsum, B. Dohn, S. Uldum, A. M. Worm, and K.
      Lind, Genitourin. Med. 69:265-269, 1993), and later, four M. genitalium strains
      were isolated (J. S. Jensen, H. T. Hansen, and K. Lind, J. Clin. Microbiol.
      34:286-291, 1996). The objective of this study was to characterize immunogenic
      proteins of M. genitalium by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis and immunoblotting by using a hyperimmune rabbit serum against M.
      genitalium G37, determine their identity by mass spectrometry, and develop an M.
      genitalium-specific enzyme-linked immunosorbent assay (ELISA) free from cross
      reactivity with M. pneumoniae antibodies. Using recombinant fragments of the C
      terminal part of MgPa (rMgPa), we developed a specific ELISA for detection of M.
      genitalium antibodies. This antigen did not bind M. pneumoniae antibodies. Using
      serum samples from the 99 men with and without urethritis, we found that 26 had
      immunoglobulin G (IgG) antibodies to M. genitalium. There was a strong
      statistically significant correlation between PCR and IgG antibodies to M.
      genitalium (odds ratio [OR], 5.9; 95% confidence interval [CI], 2.3 to 21.5; P =
      0.002). Furthermore, men with recurrent urethritis were more likely to have
      antibodies to M. genitalium than were those without recurrent urethritis (OR,
      4.0; 95% CI, 1.1 to 14.5; P = 0.0383) and they had significantly higher antibody
      titers. By use of the rMgPa ELISA, this study further substantiates the
      importance of M. genitalium as a cause of male urethritis.

PMID- 16893994
TI  - DNA vaccine using Mycobacterium bovis Ag85B antigen induces partial protection
      against experimental infection in BALB/c mice.
AB  - Bovine tuberculosis is a major cause of economic loss in countries where it is
      endemic, and in some countries, it may be a significant zoonotic disease problem.
      Therefore, new strategies for vaccine development are required, and among them,
      genetic immunization has potential value. The main goal of this study was to test
      the Mycobacterium bovis Ag85B gene as a DNA vaccine following challenge with an
      M. bovis virulent strain (ATCC 19274). Groups of BALB/c mice (n = 10) were
      immunized four times intramuscularly with the pCI-Ag85B construct or the pCI
      vector alone as the control. High titers of total immunoglobulin G (IgG), IgG1,
      and IgG2a anti-Ag85B were measured in pCI-Ag85B immunized mice when compared to
      the pCI control group. Regarding cellular immunity, significant levels of gamma
      interferon (IFN-gamma) (1,100 +/- 157 pg/ml) and tumor necrosis factor alpha (650
      +/- 42 pg/ml) but not interleukin-4 were detected in splenocyte culture
      supernatants of pCI-Ag85B-vaccinated mice following stimulation with recombinant
      Ag85B. Further, the main source of IFN-gamma is CD8(+) T cells, as demonstrated
      by intracellular cytokine staining. As far as protection, a significant reduction
      in bacterial load in spleens (P < 0.05) was detected in pCI-Ag85B-immunized mice
      compared to the pCI vector control group. The results obtained here suggest that
      use of the Ag85B DNA vaccine is a promising strategy to control M. bovis
      infection due to its ability to induce a Th1 type of immune response. However,
      protective efficacy needs to be improved, since partial protection was achieved
      in spleens but not in lungs of vaccinated mice.

PMID- 16893995
TI  - Group B streptococcal type II and III conjugate vaccines: physicochemical
      properties that influence immunogenicity.
AB  - Recent efforts toward developing vaccines against group B streptococci (GBS) have
      focused on increasing the immunogenicity of GBS polysaccharides by conjugation to
      carrier proteins. However, partial depolymerization of GBS polysaccharides for
      the production of vaccines is a difficult task because of their acid-labile,
      antigenically critical sialic acids. Here we report a method for the partial
      depolymerization of type II and III polysaccharides by mild deaminative cleavage
      to antigenic fragments with reducing-terminal 2,5-anhydro-d-mannose residues.
      Through the free aldehydes of their newly formed end groups, the fragments were
      conjugated to tetanus toxoid by reductive amination. The resulting conjugates
      stimulated the production in animals of high-titer type II- and III-specific
      antibodies which induced opsonophagocytic killing of type II and III strains of
      group B streptococci. For the type II conjugates, immunogenicity increased as
      oligosaccharide size decreased, whereas for type III conjugates, the size of the
      oligosaccharides did not significantly influence immunogenicity. When
      oligosaccharides of defined size were conjugated through sialic acid residues,
      the resulting cross-linkages were shown to affect immunogenicity. When
      oligosaccharides were conjugated through terminal aldehyde groups generated by
      deamination, modification of the exocyclic chain of sialic acid did not influence
      immunogenicity.

PMID- 16893997
TI  - Human neutralizing Fab molecules against severe acute respiratory syndrome
      coronavirus generated by phage display.
AB  - Human recombinant Fab fragments specific for the spike protein of severe acute
      respiratory syndrome coronavirus (SARS-CoV) were screened from a human Fab
      library, which was generated from RNAs from peripheral lymphocytes of
      convalescent SARS patients. Among 50 randomly picked clones, 12 Fabs specially
      reacted with S protein by an enzyme-linked immunosorbent assay. The
      microneutralizing test showed that one clone, designated M1A, had neutralizing
      activity on Vero E6 cells against SARS-CoV. DNA sequence analysis indicated that
      the light- and heavy-chain genes of M1A Fab belong to the kappa2a and 4f
      families, respectively. A neutralizing test on purified M1A demonstrated that 0.5
      mg/ml of M1A completely inhibited SARS-CoV activity, with an absence of
      cytopathic effect for 7 days. Real-time fluorescence reverse transcription-PCR
      also proved the neutralizing capacity of M1A. These data showed that the number
      of virus copies was significantly reduced in the M1A-treated group, suggesting an
      important role for M1A in passive immunoprophylaxis against the SARS virus.

PMID- 16893996
TI  - The gamma interferon (IFN-gamma) mimetic peptide IFN-gamma (95-133) prevents
      encephalomyocarditis virus infection both in tissue culture and in mice.
AB  - We have demonstrated previously that the C-terminal gamma interferon (IFN-gamma)
      mimetic peptide consisting of residues 95 to 133 [IFN-gamma(95-133)], which
      contains the crucial IFN-gamma nuclear localization sequence (NLS), has antiviral
      activity in tissue culture. Here we evaluate the efficacy of this peptide and its
      derivatives first in vitro and then in an animal model of lethal viral infection
      with the encephalomyocarditis (EMC) virus. Deletion of the NLS region from the
      IFN-gamma mimetic peptide IFN-gamma(95-133) resulted in loss of antiviral
      activity. However, the NLS region does not have antiviral activity in itself.
      Replacing the NLS region of IFN-gamma(95-133) with the NLS region of the simian
      virus 40 large T antigen retains the antiviral activity in tissue culture. IFN
      gamma(95-133) prevented EMC virus-induced lethality in mice in a dose-dependent
      manner compared to controls. Mice treated with IFN-gamma(95-133) had no or low
      EMC virus titers in their internal organs, whereas control mice had consistently
      high viral titers, especially in the heart tissues. Injection of B8R protein,
      which is encoded by poxviruses as a defense mechanism to neutralize host IFN
      gamma, did not inhibit IFN-gamma(95-133) protection against a lethal dose of EMC
      virus, whereas mice treated with rat IFN-gamma were not protected. The data
      presented here show that the IFN-gamma mimetic peptide IFN-gamma(95-133) prevents
      EMC virus infection in vivo and in vitro and may have potential against other
      lethal viruses, such as the smallpox virus, which encodes the B8R protein.

PMID- 16893998
TI  - Immunotargeting with CD154 (CD40 ligand) enhances DNA vaccine responses in ducks.
AB  - Engagement of CD154 on activated T cells with CD40 on antigen-presenting cells
      (APCs) potentiates adaptive immune responses in mammals. Soluble multimeric forms
      of CD154 have been used as an adjuvant or in immunotargeting strategies to
      enhance vaccine responses. The objective of our study was to examine the ability
      of duck CD154 (DuCD154) to enhance DNA vaccine responses in the duck hepatitis B
      model. Constructs were generated to express the functional domain of DuCD154
      (tCD154), truncated duck hepatitis B virus (DHBV) core antigen (tcore) and
      chimera of tcore fused to tCD154 (tcore-tCD154). Expression in LMH cells
      demonstrated that all proteins were secreted and that tCD154 and tcore-tCD154
      formed multimers. Ducks immunized with the plasmid ptcore-tCD154 developed
      accelerated and enhanced core-specific antibody responses compared to ducks
      immunized with ptcore or ptcore plus ptCD154. Antibody responses were better
      sustained in both ptcore-tCD154- and ptcore plus ptCD154-immunized ducks. Core
      specific proliferative responses of duck peripheral blood mononuclear cells were
      enhanced in ducks immunized with ptcore-tCD154 or ptcore alone. This study
      suggests that the role of CD154 in the regulation of adaptive immune responses
      had already evolved before the divergence of birds and mammals. Thus, targeting
      of antigens to APCs with CD154 is an effective strategy to enhance DNA vaccine
      responses not only in mammalian species but also in avian species.

PMID- 16894000
TI  - Use of immunoglobulin g avidity to determine the course of disease in visceral
      and post-kala-azar dermal leishmaniasis patients.
AB  - In the present study, anti-Leishmania immunoglobulin G (IgG) avidity was used to
      estimate the approximate time of disease manifestation. Significant differences
      (P < 0.0001) were found between the levels of anti-rKE-16 IgG avidity in
      leishmaniasis patients with recent and chronic diseases. More than 76% of
      patients with an illness duration of less than 6 months had avidity of less than
      70%, 94% of patients had less than 80% avidity, and all (100%) patients with
      illness of more than 6 months had avidity values higher than 70%. The study
      showed that avidity could successfully be used to pinpoint the duration of
      leishmaniasis.

PMID- 16893999
TI  - A novel double-antigen sandwich enzyme-linked immunosorbent assay for Measurement
      of Antibodies against rabies virus.
AB  - A novel double-antigen sandwich enzyme-linked immunosorbent assay (ELISA) was
      developed to measure rabies antibodies in dogs. In contrast to the 4 days
      required for detecting rabies antibody with conventional rabies antibody virus
      neutralization assays, this ELISA can be completed in hours, without using live
      virus, in routine laboratories.

PMID- 16894002
TI  - Delay in the diagnosis of acute myocardial infarction: effect on quality of care
      and its assessment.
AB  - BACKGROUND: Delay in diagnosis of acute myocardial infarction (AMI) may affect
      quality of care and its assessment. OBJECTIVES: To examine over time the
      frequency of delay in AMI diagnosis and the effect of this delay on the quality
      of patient care and its assessment. METHODS: The authors examined the trend in
      coded admission diagnosis, age, comorbidities, procedures during hospitalization,
      and discharge status for 42,406 Connecticut Medicare cases with the principal
      discharge diagnosis of AMI for the time period 1992 through 2001. For 2,583 cases
      discharged in 1992 and 1993 and for 1,398 cases discharged in 1998 through 2001,
      the rates of administration of aspirin (ASA) and beta blocker (BB) on admission
      and discharge, by admission diagnosis, were ascertained. RESULTS: For patients
      discharged with the principal diagnosis of AMI over the decade examined, the
      proportion with this diagnosis on admission fell (59% to 40%, p < 0.001), the
      proportion with a non-acute coronary syndrome (ACS) admission diagnosis rose (18%
      to 26%, p < 0.001), and the population aged (proportion older than 85 years of
      age increased from 16% to 28%, p < 0.001). Patients with ACS as the admission
      diagnosis more frequently received cardiac catheterization (during 2000-2001, 39%
      versus 17%, p < 0.001), percutaneous coronary intervention (19% versus 4%, p <
      0.001), and evidence-based therapy; during 1998-2001, opportunities to give ASA
      or BB on admission were fulfilled for 88% versus 73% (p < 0.001), and on
      discharge, for 87% versus 74% (p < 0.005). CONCLUSIONS: The diagnosis of AMI is
      delayed after admission for a significant proportion of cases who receive care
      that is measured to be of lower quality. There is a need to more effectively
      diagnose and treat these cases with delayed diagnosis and to develop new quality
      measures to address changes in the characteristics of patients who are
      hospitalized with AMI.

PMID- 16894001
TI  - Reduced expression of toll-like receptor 2 on peripheral monocytes in patients
      with chronic hepatitis B.
AB  - Persistent infection with hepatitis B virus (HBV) likely depends on viral
      inhibition of host defenses. We report that chronic hepatitis B e antigen
      positive HBV infection is associated with a significant reduction in peripheral
      blood monocyte expression of Toll-like receptor 2, a key component of innate
      immunity, thereby providing a mechanism by which wild-type HBV may establish
      persistent infection.

PMID- 16894003
TI  - Emergency department sexually transmitted disease and human immunodeficiency
      virus screening: findings from a national survey.
AB  - OBJECTIVES: To use a previously conducted national physician survey to determine
      the extent of human immunodeficiency virus (HIV) and sexually transmitted disease
      (STD) screening by emergency physicians compared with physicians practicing in
      other settings (primary care offices, hospital ambulatory care clinics, or
      other). METHODS: From the survey responses, the authors determined the percentage
      of emergency physicians and physicians not practicing in EDs screening various
      patient groups for syphilis, gonorrhea, chlamydia, and HIV. Additional data from
      the survey (for practice location, physician gender, and patient demographics of
      race and gender) were used in multivariate logistic regressions to determine
      adjusted odds ratios (ORs). RESULTS: Of 3,838 survey respondents providing
      answers to all questions analyzed for this study, 401 (10.5%) practiced in an
      emergency department. Of the remaining 3,437 physicians, 89% practiced in primary
      care offices or hospital ambulatory care clinics. Based on unadjusted ORs,
      emergency physicians were less likely than physicians not practicing in EDs to
      screen for all STDs and HIV in all patient groups (men, nonpregnant women, and
      pregnant women), although the differences in screening rates in male patients for
      chlamydia or gonorrhea were not significant. The adjusted ORs varied from 0.136
      (for HIV screening of pregnant women) to 1.177 (for gonorrhea screening of
      pregnant women). All adjusted ORs that were significant at p < 0.05 were < 1.0.
      CONCLUSIONS: Although prior research has shown that STD and HIV rates are
      relatively high in emergency department patients compared with the population as
      a whole, screening rates are lower than in other settings. Addressing barriers
      may increase screening rates.

PMID- 16894004
TI  - Comparison of the medical priority dispatch system to an out-of-hospital patient
      acuity score.
AB  - BACKGROUND: Although the Medical Priority Dispatch System (MPDS) is widely used
      by emergency medical services (EMS) dispatchers to determine dispatch priority,
      there is little evidence that it reflects patient acuity. The Canadian Triage and
      Acuity Scale (CTAS) is a standard patient acuity scale widely used by Canadian
      emergency departments and EMS systems to prioritize patient care requirements.
      OBJECTIVES: To determine the relationship between MPDS dispatch priority and out
      of-hospital CTAS. METHODS: All emergency calls on a large urban EMS
      communications database for a one-year period were obtained. Duplicate calls,
      nonemergency transfers, and canceled calls were excluded. Sensitivity and
      specificity to detect high-acuity illness, as well as positive predictive value
      (PPV) and negative predictive value (NPV), were calculated for all protocols.
      RESULTS: Of 197,882 calls, 102,582 met inclusion criteria. The overall
      sensitivity of MPDS was 68.2% (95% confidence interval [CI] = 67.8% to 68.5%),
      with a specificity of 66.2% (95% CI = 65.7% to 66.7%). The most sensitive
      protocol for detecting high acuity of illness was the breathing-problem protocol,
      with a sensitivity of 100.0% (95% CI = 99.9% to 100.0%), whereas the most
      specific protocol was the one for psychiatric problems, with a specificity of
      98.1% (95% CI = 97.5% to 98.7%). The cardiac-arrest protocol had the highest PPV
      (92.6%, 95% CI = 90.3% to 94.3%), whereas the convulsions protocol had the
      highest NPV (85.9%, 95% CI = 84.5% to 87.2%). The best-performing protocol
      overall was the cardiac-arrest protocol, and the protocol with the overall
      poorest performance was the one for unknown problems. Sixteen of the 32 protocols
      performed no better than chance alone at identifying high-acuity patients.
      CONCLUSIONS: The Medical Priority Dispatch System exhibits at least moderate
      sensitivity and specificity for detecting high acuity of illness or injury. This
      performance analysis may be used to identify target protocols for future
      improvements.

PMID- 16894005
TI  - A comparison of five simplified scales to the out-of-hospital Glasgow Coma Scale
      for the prediction of traumatic brain injury outcomes.
AB  - BACKGROUND: The 15-point Glasgow Coma Scale (GCS) frequently is used in the
      initial evaluation of traumatic brain injury (TBI) in out-of-hospital settings.
      We hypothesized that the GCS might be unnecessarily complex for out-of-hospital
      use. OBJECTIVES: To assess whether a simpler scoring system might demonstrate
      similar accuracy in the prediction of TBI outcomes. METHODS: We performed a
      retrospective analysis of a trauma registry consisting of patients evaluated at
      our Level 1 trauma center from 1990 to 2002. The ability of out-of-hospital GCS
      scores to predict four clinically relevant TBI outcomes (emergency intubation,
      neurosurgical intervention, brain injury, and mortality) by using areas under
      receiver operating characteristic curves (AUROCs) was calculated. The same
      analyses for five simplified scales were performed, and compared with the
      predictive accuracies of the total GCS score. RESULTS: In this evaluation of
      7,233 trauma patients over a 12-year period of time, the AUROCs for the total GCS
      score were 0.83 (95% confidence interval [CI] = 0.81 to 0.84) for emergency
      intubation, 0.86 (95% CI = 0.85 to 0.88) for neurosurgical intervention, 0.83
      (95% CI = 0.82 to 0.84) for brain injury, and 0.89 (95% CI = 0.88 to 0.90) for
      mortality. The five simplified scales approached the performance of the total GCS
      score for all clinical outcomes. CONCLUSIONS: In the evaluation of injured
      patients, five simplified neurological scales approached the performance of the
      total GCS score for the prediction of four clinically relevant TBI outcomes.

PMID- 16894006
TI  - Quality-of-care measures in emergency medicine: when will they come? What will
      they look like?

PMID- 16894008
TI  - Epidemiologic features of invasive pneumococcal disease in Belgian children:
      passive surveillance is not enough.
AB  - BACKGROUND: Reliable epidemiologic surveillance of infectious diseases is
      important for making rational choices for public health issues such as
      vaccination strategies. In Belgium, as in most European countries, surveillance
      relies on voluntary passive reporting from microbiology laboratories; therefore,
      reported incidence rates are probably inaccurate. METHODS: We conducted national,
      active, laboratory-based and clinically based surveillance of invasive
      pneumococcal disease in young children. RESULTS: During the study period, the
      incidences of invasive pneumococcal disease in children < 2 years of age (104.4
      cases per 10(5) person-years and 16.1 cases per 10(5) person-years for invasive
      pneumococcal disease and meningitis, respectively) and in children 0 to 59 months
      of age (59.5 cases per 10(5) person-years for invasive pneumococcal disease and
      7.7 cases per 10(5) person-years for meningitis) were twice those reported
      previously through the passive surveillance system. Overall, 67% of the
      Streptococcus pneumoniae strains isolated from children < 5 years of age belonged
      to 7-valent pneumococcal conjugate vaccine serotypes and 18% to vaccine-related
      serotypes (mainly serotype 19A). Erythromycin resistance was frequent, especially
      among children < 2 years of age (59%). CONCLUSIONS: Under-reporting can explain
      the reported low incidence of invasive pneumococcal disease in countries (such as
      Belgium) that depend on a passive epidemiologic surveillance system, which could
      lead to erroneous choices in vaccination policies. There is a need for an active
      system of epidemiologic surveillance for vaccine-preventable diseases such as
      invasive pneumococcal disease, at the national or European level.

PMID- 16894009
TI  - Churg-Strauss syndrome in children: a clinical and pathologic review.
AB  - Churg-Strauss syndrome is a vasculitis accompanied by asthma and eosinophilia. It
      is generally considered a disease of adults; occurrence in children has been
      reported infrequently. Here we report 2 pediatric patients with Churg-Strauss
      syndrome manifesting with prominent pulmonary involvement. One, a 16-year-old
      with a previous history of asthma, presented with pleuritic chest pain and a
      peripheral pulmonary nodule complicated by an eosinophilic pleural effusion. The
      other patient presented at age 6 with cough, weight loss, and radiographic
      infiltrates. Lung biopsies revealed elements characteristic of Churg-Strauss
      syndrome, including eosinophilic microabscesses and vasculitis. Three- and 5-year
      follow-up showed continued symptoms in both patients despite medical therapy.
      Both patients illustrate many of the typical features of Churg-Strauss syndrome.
      We report these cases to expand the scant knowledge about Churg-Strauss syndrome
      in pediatric patients and to heighten awareness that this serious disease may
      affect the pediatric population. The relevant literature on Churg-Strauss
      syndrome, with specific reference to childhood cases, is reviewed.

PMID- 16894010
TI  - Cognitive function and behavior of children with adenotonsillar hypertrophy
      suspected of having obstructive sleep-disordered breathing.
AB  - OBJECTIVE: The purpose of this study was to determine whether risks of impaired
      cognitive function could be predicted for children or groups of children with
      adenotonsillar hypertrophy who were suspected of having obstructive sleep
      disordered breathing, from historical and polysomnographic variables used
      separately or in combination. METHODS: We studied 114 consecutive 6- to 12-year
      old children with adenotonsillar hypertrophy, who were referred because of
      suspected obstructive sleep-disordered breathing, with questionnaires, assessment
      of tonsil size, general and memory cognitive tests, and attended polysomnography
      with the use of nasal pressure recording to detect flow. RESULTS: There were
      important significant relationships between snore group (snored every night
      versus less often), sleep efficiency, and race and 2 of 3 general cognitive tests
      (vocabulary and similarities). Significant but weaker relationships were observed
      between sleep latency and 2 memory indices (verbal memory and general memory) and
      between sleep efficiency and 2 behavior indices (attention-deficit/hyperactivity
      disorder summary and hyperactive-impulsive summary). The number of episodes of
      apnea and hypopnea per 1 hour of sleep predicted the vocabulary score as well as
      did the snore group, but it did not predict other tests as well as other
      variables. Tonsil size did not predict any cognitive or behavior score.
      Confidence intervals for group means were small, whereas prediction intervals for
      individual children were large. CONCLUSIONS: Risk of impaired cognitive function
      and behavior can be predicted from snoring history, sleep efficiency, sleep
      latency, and race but not tonsil size. The combination of snoring history and
      polysomnographic variables predicted impaired cognitive scores better than did
      either alone. The snoring history predicted more test scores than the number of
      episodes of apnea and hypopnea per 1 hour of sleep.

PMID- 16894011
TI  - Childhood acute renal failure: 22-year experience in a university hospital in
      southern Thailand.
AB  - OBJECTIVES: The objectives of this study were to review the prevalence, cause,
      and morbidity and mortality rates of acute renal failure in a large tertiary care
      institution in southern Thailand, to examine any differences in acute renal
      failure cases diagnosed during a 22-year period, and to determine the risk
      factors indicating death. METHODS: The case records for children 1 month to 17
      years of age who were diagnosed as having acute renal failure between February
      1982 and December 2004, in the Department of Pediatrics, Songklanagarind
      Hospital, in southern Thailand, were reviewed. RESULTS: A total of 311 children
      with 318 episodes of acute renal failure were included, that is, 177 boys (55.7%)
      and 141 girls (44.3%), 1 month to 16.7 years of age (mean age: 7.6 +/- 5.1 years;
      median age: 7.8 years). The causes of acute renal failure in each age group were
      significantly different. Overall, sepsis was the major cause of acute renal
      failure, accounting for 68 episodes (21.4%), followed by hypovolemia,
      poststreptococcal glomerulonephritis, systemic lupus erythematosus, and
      infectious diseases. Renal replacement therapy was performed in 55 cases (17.3%).
      The overall mortality rate was 41.5%. Logistic regression analysis showed that
      disease groups and creatinine levels were significant independent predictors of
      outcomes. CONCLUSIONS: The incidence of acute renal failure in Songklanagarind
      Hospital was 0.5 to 9.9 cases per 1000 pediatric patients, with a mortality rate
      of 41.5%. Sepsis was a major cause of acute renal failure and death. Causes of
      acute renal failure and serum creatinine levels were significant independent
      predictors of death.

PMID- 16894012
TI  - Low-grade chronic inflammation in regions of the normal mouse arterial intima
      predisposed to atherosclerosis.
AB  - Atherosclerotic lesions develop in regions of arterial curvature and branch
      points, which are exposed to disturbed blood flow and have unique gene expression
      patterns. The cellular and molecular basis for atherosclerosis susceptibility in
      these regions is not completely understood. In the intima of atherosclerosis
      predisposed regions of the wild-type C57BL/6 mouse aorta, we quantified increased
      expression of several proinflammatory genes that have been implicated in
      atherogenesis, including vascular cell adhesion molecule-1 (VCAM-1) and a
      relative abundance of dendritic cells, but only occasional T cells. In contrast,
      very few intimal leukocytes were detected in regions resistant to
      atherosclerosis; however, abundant macrophages, including T cells, were found
      throughout the adventitia (Adv). Considerably lower numbers of intimal CD68+
      leukocytes were found in inbred atherosclerosis-resistant C3H and BALB/c mouse
      strains relative to C57BL/6 and 129; however, leukocyte distribution throughout
      the Adv of all strains was similar. The predominant mechanism for the
      accumulation of intimal CD68+ cells was continued recruitment of bone marrow
      derived blood monocytes, suggestive of low-grade chronic inflammation. Local
      proliferation of intimal leukocytes was low. Intimal CD68+ leukocytes were
      reduced in VCAM-1-deficient mice, suggesting that mechanisms of leukocyte
      accumulation in the intima of normal aorta are analogous to those in
      atherosclerosis.

PMID- 16894015
TI  - Do all types of human research need ethics committee approval?

PMID- 16894016
TI  - Myofibroblast or smooth muscle: do in vitro systems adequately replicate tissue
      smooth muscle?

PMID- 16894013
TI  - The in vivo pattern of AID targeting to immunoglobulin switch regions deduced
      from mutation spectra in msh2-/- ung-/- mice.
AB  - Immunoglobulin (Ig) class switching is initiated by deamination of C-->U within
      the immunoglobulin heavy chain locus, catalyzed by activation-induced deaminase
      (AID). In the absence of uracil-DNA glycosylase (UNG) and the homologue of
      bacterial MutS (MSH)-2 mismatch recognition protein, the resultant U:G lesions
      are not processed into switching events but are fixed by replication allowing
      sites of AID-catalyzed deamination to be identified by the resulting C-->T
      mutations. We find that AID targets cytosines in both donor and acceptor switch
      regions (S regions) with the deamination domains initiating approximately 150
      nucleotides 3' of the I exon start sites and extending over several kilobases
      (the IgH intronic enhancer is spared). Culturing B cells with interleukin 4 or
      interferon gamma specifically enhanced deamination around Sgamma1 and Sgamma2a,
      respectively. Mutation spectra suggest that, in the absence of UNG and MSH2, AID
      may occasionally act at the mu switch region in an apparently processive manner,
      but there is no marked preference for targeting of the transcribed versus
      nontranscribed strand (even in areas capable of R loop formation). The data are
      consistent with switch recombination being triggered by transcription-associated,
      strand-symmetric AID-mediated deamination at both donor and acceptor S regions
      with cytokines directing isotype specificity by potentiating AID recruitment to
      the relevant acceptor S region.

PMID- 16894017
TI  - A glitch in the switch? Of endotoxin, CD14, and allergy.

PMID- 16894018
TI  - American Thoracic Society statement on research priorities in respiratory
      nursing.

PMID- 16894019
TI  - Long-term efficacy of acetazolamide on Cheyne-Stokes respiration in congestive
      heart failure.

PMID- 16894021
TI  - The scope and impact of treatment of latent tuberculosis infection in the United
      States and Canada.

PMID- 16894022
TI  - Editorial: Imaging to detect early endocrine cancers.

PMID- 16894023
TI  - Editorial: Individual differences in the hormonal control of appetite: a step
      toward a (more) successful treatment of childhood overweight?

PMID- 16894024
TI  - Effects of long-term object familiarity on event-related potentials in the
      monkey.
AB  - Although some change in the neural representation of an object must occur as it
      becomes familiar, the nature of this change is not fully understood. In humans,
      it has been shown that the N170-an evoked visual potential-is enhanced for
      classes of objects for which people have visual expertise. In this study, we
      explored whether monkeys show a similar modulation in event-related potential
      (ERP) amplitude as a result of long-term familiarity by recording ERPs with
      chronically implanted electrodes over extended training periods spanning many
      sessions. In each of 3 experiments, we found larger amplitude visual evoked
      responses to highly familiar images for the time period of 120-250 ms after
      stimulus onset. This difference was found when the monkeys were trained in an
      individual-level discrimination task, in a task that required only color
      discrimination, and even following a viewing-only task. We thus observed this
      familiarity effect across several tasks and different object categories and
      further found that the difference between "familiar" and "novel" became smaller
      as the animals gained experience with the previously unfamiliar objects across
      multiple test sessions. These data suggest that changes in visual responses
      associated with familiarity are evident early in the evoked visual response, are
      robust, and may be automatic, driven at least in part by repeated object
      exposure.

PMID- 16894025
TI  - Toward understanding the insight paradox: internalized stigma moderates the
      association between insight and social functioning, hope, and self-esteem among
      people with schizophrenia spectrum disorders.
AB  - Research has paradoxically linked awareness of illness to both better function
      outcomes and lesser hope and self-esteem. One possible explanation for these
      findings is that acceptance of having schizophrenia may impact outcomes
      differently depending on the meanings the person attaches to this acceptance,
      particularly whether he or she accepts stigmatizing beliefs about mental illness.
      To explore this possibility we performed a cluster analysis of 75 persons with
      schizophrenia spectrum disorders based on single measures of insight using the
      Positive and Negative Syndrome Scale, internalized stigma using the Internalized
      Stigma of Mental Illness Scale, and compared groups on concurrent assessments of
      hope and self-esteem. Three groups were produced by the cluster analyses: low in
      sight/mild stigma (n = 23), high insight/minimal stigma (n = 25), and high
      insight/moderate stigma (n = 27). As predicted, analysis of variance-comparing
      groups revealed that the high insight/moderate stigma group had significantly the
      lowest levels of hope on the Beck Hopelessness Scale and self-esteem using the
      Multidimensional Self-esteem Inventory. As predicted, the high insight/minimal
      stigma group also had significantly less impaired social function than the other
      groups. Implications for assisting persons to come to cope with awareness of
      illness and stigma are discussed.

PMID- 16894026
TI  - Predictive validity of proposed remission criteria in first-episode schizophrenic
      patients responding to antipsychotics.
AB  - The objective of this study was to examine the predictive validity of the
      remission criteria proposed by Andreasen et al in first-episode patients
      responding to antipsychotics. Antipsychotic responsive patients with first
      episode schizophrenia showing symptom remission (n = 60) were compared with
      patients who did not fulfill the proposed criteria (n = 65). Outcome in terms of
      symptom severity, social functioning, and quality of life was assessed after 18
      months. Patients in the remission group showed a significantly better outcome
      during follow-up on all Positive and Negative Syndrome Scale subscale scores
      (positive, negative, and general symptom subscales) and a significantly higher
      level of social functioning. Quality of life did not differ between groups. The
      proposed multidimensional criteria for symptomatic remission convey significant
      information when applied to first-episode patients who responded to
      antipsychotics, predicting outcome on the domains of both psychopathology and
      social functioning. The criteria represent a practicable benchmark with clinical
      relevance. Their implementation should be promoted in research settings, clinical
      practice, and routine outcome assessment procedures.

PMID- 16894027
TI  - The influence of money on medical science.

PMID- 16894028
TI  - Apoptosis inhibition by the human DEK oncoprotein involves interference with p53
      functions.
AB  - The DEK proto-oncogene has been associated with human carcinogenesis-either as a
      fusion with the CAN nucleoporin protein or when transcriptionally upregulated.
      Mechanisms of intracellular DEK functions, however, have remained relatively
      unexplored. We have recently demonstrated that DEK expression is induced by the
      high-risk human papillomavirus (HPV) E7 protein in a manner which is dependent
      upon retinoblastoma protein function and have implicated DEK in the inhibition of
      cellular senescence. Additionally, overexpression of DEK resulted in significant
      life span extension of primary human keratinocytes. In order to determine whether
      DEK expression is required for cellular proliferation and/or survival, we
      monitored cellular responses to the knockdown of DEK in cancer and primary cells.
      The results indicate that DEK expression protects both HPV-positive cancer and
      primary human cells from apoptotic cell death. Cell death in response to DEK
      depletion was accompanied by increased protein stability and transcriptional
      activity of the p53 tumor suppressor and consequent upregulation of known p53
      target genes such as p21CIP and Bax. Consistent with a possible role for p53 in
      DEK-mediated cell death inhibition, the p53-negative human osteosarcoma cell line
      SAOS-2 was resistant to the knockdown of DEK. Finally, expression of a dominant
      negative p53 miniprotein inhibited DEK RNA interference-induced p53
      transcriptional induction, as well as cell death, thus directly implicating p53
      activation in the observed apoptotic phenotype. These findings suggest a novel
      role for DEK in cellular survival, involving the destabilization of p53 in a
      manner which is likely to contribute to human carcinogenesis.

PMID- 16894029
TI  - Repression of Nanog gene transcription by Tcf3 limits embryonic stem cell self
      renewal.
AB  - The dual function of stem cells requires them not only to form new stem cells
      through self-renewal but also to form lineage-committed cells through
      differentiation. Embryonic stem cells (ESC), which are derived from the
      blastocyst inner cell mass, retain properties of self-renewal and the potential
      for lineage commitment. To balance self-renewal and differentiation, ESC must
      carefully control the levels of several transcription factors, including Nanog,
      Sox2, and Oct4. While molecular mechanisms promoting transcription of these genes
      have been described, mechanisms preventing excessive levels in self-renewing ESC
      remain unknown. By examining the function of the TCF family of transcription
      factors in ESC, we have found that Tcf3 is necessary to limit the steady-state
      levels of Nanog mRNA, protein, and promoter activity in self-renewing ESC.
      Chromatin immunoprecipitation and promoter reporter assays showed that Tcf3 bound
      to a promoter regulatory region of the Nanog gene and repressed its
      transcriptional activity in ESC through a Groucho interaction domain-dependent
      process. The absence of Tcf3 caused delayed differentiation of ESC in vitro as
      elevated Nanog levels persisted through 5 days of embryoid body formation. These
      new data support a model wherein Tcf3-mediated control of Nanog levels allows
      stem cells to balance the creation of lineage-committed and undifferentiated
      cells.

PMID- 16894030
TI  - The Drosophila inhibitor of apoptosis protein DIAP2 functions in innate immunity
      and is essential to resist gram-negative bacterial infection.
AB  - The founding member of the inhibitor of apoptosis protein (IAP) family was
      originally identified as a cell death inhibitor. However, recent evidence
      suggests that IAPs are multifunctional signaling devices that influence diverse
      biological processes. To investigate the in vivo function of Drosophila
      melanogaster IAP2, we have generated diap2 null alleles. diap2 mutant animals
      develop normally and are fully viable, suggesting that diap2 is dispensable for
      proper development. However, these animals were acutely sensitive to infection by
      gram-negative bacteria. In Drosophila, infection by gram-negative bacteria
      triggers the innate immune response by activating the immune deficiency (imd)
      signaling cascade, a NF-kappaB-dependent pathway that shares striking
      similarities with the pathway of mammalian tumor necrosis factor receptor 1
      (TNFR1). diap2 mutant flies failed to activate NF-kappaB-mediated expression of
      antibacterial peptide genes and, consequently, rapidly succumbed to bacterial
      infection. Our genetic epistasis analysis places diap2 downstream of or in
      parallel to imd, Dredd, Tak1, and Relish. Therefore, DIAP2 functions in the host
      immune response to gram-negative bacteria. In contrast, we find that the
      Drosophila TNFR-associated factor (Traf) family member Traf2 is dispensable in
      resistance to gram-negative bacterial infection. Taken together, our genetic data
      identify DIAP2 as an essential component of the Imd signaling cascade, protecting
      the organism from infiltrating microbes.

PMID- 16894032
TI  - Detection of chronic kidney disease in patients with or at increased risk of
      cardiovascular disease: a science advisory from the American Heart Association
      Kidney And Cardiovascular Disease Council; the Councils on High Blood Pressure
      Research, Cardiovascular Disease in the Young, and Epidemiology and Prevention;
      and the Quality of Care and Outcomes Research Interdisciplinary Working Group:
      developed in collaboration with the National Kidney Foundation.
AB  - Chronic kidney disease (CKD) occurs commonly in patients with cardiovascular
      disease. In addition, CKD is a risk factor for the development and progression of
      cardiovascular disease. In this advisory, we present recommendations for the
      detection of CKD in patients with cardiovascular disease. CKD can be reliably
      detected with the combined use of the Modification of Diet in Renal Disease
      equation to estimate glomerular filtration rate and a sensitive test to detect
      microalbuminuria. All patients with cardiovascular disease should be screened for
      evidence of kidney disease with these two determinations.

PMID- 16894031
TI  - mTOR-independent translational control of the extrinsic cell death pathway by
      RalA.
AB  - Oncogenic potential is associated with translational regulation, and the
      prevailing view is that oncogenes use mTOR-dependent pathways to up-regulate the
      synthesis of proteins critical for transformation. In this study, we show that
      RalA, a key mediator of Ras transformation, is also linked to the translational
      machinery. At least part of this linkage, however, is independent of mTOR and
      acts through RalBP1 to suppress cdc42-mediated activation of S6 kinase and the
      translation of the antiapoptotic protein FLIP(S). This action, rather than
      contributing to transformation, opens a latent tumor-suppressive mechanism that
      can be activated by tumor necrosis factor-related apoptosis-inducing ligand.
      These results show that the translational machinery is linked to tumor
      suppression as well as cell-proliferative pathways and that the reestablishment
      of cell death pathways by activation of the Ral oncogenic program provides a
      means for selective therapeutic targeting of Ral-driven malignancies.

PMID- 16894033
TI  - Local controlled intramyocardial delivery of platelet-derived growth factor
      improves postinfarction ventricular function without pulmonary toxicity.
AB  - BACKGROUND: Local delivery methods can target therapies to specific tissues and
      potentially avoid toxicity to other organs. Platelet-derived growth factor can
      protect the myocardium, but it also plays an important role in promoting
      pulmonary hypertension. It is not known whether local myocardial delivery of
      platelet-derived growth factor during myocardial infarction (MI) can lead to
      sustained cardiac benefit without causing pulmonary hypertension. METHODS AND
      RESULTS: We performed a randomized and blinded experiment of 127 rats that
      survived experimental MI or sham surgery. We delivered platelet-derived growth
      factor (PDGF)-BB with self-assembling peptide nanofibers (NFs) to provide
      controlled release within the myocardium. There were 6 groups with n > or = 20 in
      each group: sham, sham+NF, sham+NF/PDGF, MI, MI+NF, and MI+NF/PDGF. Serial
      echocardiography from 1 day to 3 months showed significant improvement of
      ventricular fractional shortening, end-systolic dimension, and end-diastolic
      dimension with local PDGF delivery (P < 0.05 for MI+NF/PDGF versus MI or MI+NF).
      Catheterization at 4 months revealed improved ventricular function in the
      controlled delivery group (left ventricular end-diastolic pressure, cardiac
      index, +dP/dt, -dP/dt, and time constant of exponential decay all P < 0.05 for
      MI+NF/P versus MI or MI+NF). Infarcted myocardial volume was reduced by NF/PDGF
      therapy (34.0 +/- 13.3% in MI, 28.9 +/- 12.9% in MI+NF, and 12.0 +/- 5.8% in
      MI+NF/PDGF; P < 0.001). There was no evidence of pulmonary toxicity from the
      therapy, with no differences in right ventricular end-systolic pressure, right
      ventricular dP/dt, bromodeoxyuridine staining, or pulmonary artery medial wall
      thickness. CONCLUSIONS: Intramyocardial delivery of PDGF by self-assembling
      peptide NFs leads to long-term improvement in cardiac performance after
      experimental infarction without apparent pulmonary toxicity. Local myocardial
      protection may allow prevention of heart failure without systemic toxicity.

PMID- 16894034
TI  - Molecular determinants of altered Ca2+ handling in human chronic atrial
      fibrillation.
AB  - BACKGROUND: Abnormal Ca2+ handling may contribute to impaired atrial
      contractility and arrhythmogenesis in human chronic atrial fibrillation (cAF).
      Here, we assessed the phosphorylation levels of key proteins involved in altered
      Ca2+ handling and contractility in cAF patients. METHODS AND RESULTS: Total and
      phosphorylation levels of Ca2+-handling and myofilament proteins were analyzed by
      Western blotting in right atrial appendages of 49 patients in sinus rhythm and 52
      cAF patients. We found a higher total activity of type 1 (PP1) and type 2A
      phosphatases in cAF, which was associated with inhomogeneous changes of protein
      phosphorylation in the cellular compartments, ie, lower protein kinase A (PKA)
      phosphorylation of myosin binding protein-C (Ser-282 site) at the thick
      myofilaments but preserved PKA phosphorylation of troponin I at the thin
      myofilaments and enhanced PKA (Ser-16 site) and Ca2+-calmodulin protein kinase
      (Thr-17 site) phosphorylation of phospholamban. PP1 activity at sarcoplasmic
      reticulum is controlled by inhibitor-1 (I-1), which blocks PP1 in its PKA
      phosphorylated form only. In cAF, the ratio of Thr-35-phosphorylated to total I-1
      was 10-fold higher, which suggests that the enhanced phosphorylation of
      phospholamban may result from a stronger PP1 inhibition by PKA
      hyperphosphorylated (activated) I-1. CONCLUSIONS: Altered Ca2+ handling in cAF is
      associated with impaired phosphorylation of myosin binding protein-C, which may
      contribute to the contractile dysfunction after cardioversion. The
      hyperphosphorylation of phospholamban probably results from enhanced inhibition
      of sarcoplasmic PP1 by hyperphosphorylated I-1 and may reinforce the leakiness of
      ryanodine channels in cAF. Restoration of sarcoplasmic reticulum-associated PP1
      function may represent a new therapeutic option for treatment of atrial
      fibrillation.

PMID- 16894035
TI  - Quantitative assessment of left ventricular size and function: side-by-side
      comparison of real-time three-dimensional echocardiography and computed
      tomography with magnetic resonance reference.
AB  - BACKGROUND: Cardiac CT (CCT) and real-time 3D echocardiography (RT3DE) are being
      used increasingly in clinical cardiology. CCT offers superb spatial and contrast
      resolution, resulting in excellent endocardial definition. RT3DE has the
      advantages of low cost, portability, and live 3D imaging without offline
      reconstruction. We sought to compare both CCT and RT3DE measurements of left
      ventricular size and function with the standard reference technique, cardiac MR
      (CMR). METHODS AND RESULTS: In 31 patients, RT3DE data sets (Philips 7500) and
      long-axis CMR (Siemens, 1.5 T) and CCT (Toshiba, 16-slice MDCT) images were
      obtained on the same day without beta-blockers. All images were analyzed to
      obtain end-systolic and end-diastolic volumes and ejection fractions using the
      same rotational analysis to eliminate possible analysis-related differences.
      Intertechnique agreement was tested through linear regression and Bland-Altman
      analyses. Repeated measurements were performed to determine intraobserver and
      interobserver variability. Both CCT and RT3DE measurements resulted in high
      correlation (r2 > 0.85) compared with CMR. However, CCT significantly
      overestimated end-diastolic and end-systolic volumes (26 and 19 mL; P < 0.05),
      resulting in a small but significant bias in ejection fraction (-2.8%). RT3DE
      underestimated end-diastolic and end-systolic volumes only slightly (5 and 6 mL),
      with no significant bias in EF (0.3%; P = 0.68). The limits of agreement with CMR
      were comparable for the 2 techniques. The variability in the CCT measurements was
      roughly half of that in either RT3DE or CMR values. CONCLUSIONS: CCT provides
      highly reproducible measurements of left ventricular volumes, which are
      significantly larger than CMR values. RT3DE measurements compared more favorably
      with the CMR reference, albeit with higher variability.

PMID- 16894036
TI  - Apolipoprotein CIII induces expression of vascular cell adhesion molecule-1 in
      vascular endothelial cells and increases adhesion of monocytic cells.
AB  - BACKGROUND: Activation of vascular endothelial cells (ECs) plays an important
      role in atherogenesis and plaque instability. Lipoproteins containing
      apolipoprotein CIII (apoCIII) predict coronary heart disease (CHD). We recently
      reported that apoCIII has a proinflammatory effect on human monocytes. In this
      study, we looked for a direct effect of apoCIII on EC expression of adhesion
      molecules, leading to monocytic cell adhesion. METHODS AND RESULTS: Treatment of
      ECs with apoCIII or apoCIII-rich VLDL caused human monocytic THP-1 cells to
      adhere to them under static condition or under laminar sheer stress (1.0
      dyne/cm2). ApoCIII increased EC expression of vascular cell adhesion molecule-1
      (VCAM-1) protein and intercellular cell adhesion molecule-1 (ICAM-1) protein (4.9
      +/- 1.5-fold and 1.4 +/- 0.5-fold versus control, respectively). Furthermore,
      apoCIII remarkably increased membrane-bound protein kinase C (PKC) beta in ECs,
      indicating activation. A selective inhibitor of PKCbeta prevented the rise in
      VCAM-1 and THP-1 cell adhesion to ECs. Moreover, exposure of ECs to apoCIII
      induced nuclear factor-kappaB (NF-kappaB) activation. PKCbeta inhibition
      abolished apoCIII-induced NF-kappaB activation, and NF-kappaB inhibition reduced
      expression of VCAM-1, each resulting in reduced THP-1 cell adhesion. ApoCIII-rich
      VLDL also activated PKCbeta and NF-kappaB in ECs and increased expression of VCAM
      1. Pretreatment of ApoCIII-rich VLDL with anti-apoCIII neutralizing antibody
      abolished its effect on PKCbeta activation. CONCLUSIONS: Our findings provide the
      first evidence that apoCIII increases VCAM-1 and ICAM-1 expression in ECs by
      activating PKCbeta and NF-kappaB, suggesting a novel mechanism for EC activation
      induced by dyslipidemia. Therefore, apoCIII-rich VLDL may contribute directly to
      atherogenesis by activating ECs and recruiting monocytes to them.

PMID- 16894037
TI  - Adiponectin and coronary heart disease: a prospective study and meta-analysis.
AB  - BACKGROUND: There is uncertainty about the association between circulating
      concentrations of adiponectin and coronary heart disease (CHD) risk. We report
      new data from a prospective study in the context of a meta-analysis of previously
      published prospective studies. METHODS AND RESULTS: We measured baseline
      adiponectin levels in stored serum samples of 589 men with fatal CHD or nonfatal
      myocardial infarction and in 1231 controls nested within a prospective study of
      5661 men (aged 40 to 59 years) recruited during 1978-1980, as well as in paired
      samples obtained 4 years apart from 221 of these participants. Baseline
      adiponectin concentrations correlated (P < 0.0001) positively with HDL
      cholesterol (r = 0.33) and inversely with C-reactive protein (r = -0.11) and BMI
      (r = -0.21), and the year-to-year consistency of adiponectin values was
      comparable to those of blood pressure and total cholesterol levels. No
      significant difference between median adiponectin levels at baseline was observed
      between cases and controls (10.2 versus 10.8 microg/mL; P = 0.5), despite the
      fact that body mass index, HDL, and C-reactive protein were all significant
      predictors of events in this cohort. The odds ratio for CHD was 0.89 (95% CI,
      0.67 to 1.18) in a comparison of men in the top third of adiponectin
      concentrations compared with those in the bottom third, similar to a meta
      analysis (including the present study) of 7 prospective studies involving a total
      of 1318 CHD cases (odds ratio, 0.84 [95% CI, 0.70 to 1.01]). CONCLUSIONS: In
      contrast to the strong associations previously reported between adiponectin
      levels and risk of type 2 diabetes, any association with CHD risk is
      comparatively moderate and requires further investigation.

PMID- 16894038
TI  - Multislice spiral computed tomography for the evaluation of stent patency after
      left main coronary artery stenting: a comparison with conventional coronary
      angiography and intravascular ultrasound.
AB  - BACKGROUND: Surveillance conventional coronary angiography (CCA) is recommended 2
      to 6 months after stent-supported left main coronary artery (LMCA) percutaneous
      coronary intervention due to the unpredictable occurrence of in-stent restenosis
      (ISR), with its attendant risks. Multislice computed tomography (MSCT) is a
      promising technique for noninvasive coronary evaluation. We evaluated the
      diagnostic performance of high-resolution MSCT to detect ISR after stenting of
      the LMCA. METHODS AND RESULTS: Seventy-four patients were prospectively
      identified from a consecutive patient population scheduled for follow-up CCA
      after LMCA stenting and underwent MSCT before CCA. Until August 2004, a 16-slice
      scanner was used (n = 27), but we switched to the 64-slice scanner after that
      period (n = 43). Patients with initial heart rates > 65 bpm received beta
      blockers, which resulted in a mean periscan heart rate of 57 +/- 7 bpm. Among
      patients with technically adequate scans (n = 70), MSCT correctly identified all
      patients with ISR (10 of 70) but misclassified 5 patients without ISR (false
      positives). Overall, the accuracy of MSCT for detection of angiographic ISR was
      93%. The sensitivity, specificity, and positive and negative predictive values
      were 100%, 91%, 67%, and 100%, respectively. When analysis was restricted to
      patients with stenting of the LMCA with or without extension into a single major
      side branch, accuracy was 98%. When both branches of the LMCA bifurcation were
      stented, accuracy was 83%. For the assessment of stent diameter and area, MSCT
      showed good correlation with intravascular ultrasound (r = 0.78 and 0.73,
      respectively). An intravascular ultrasound threshold value > or = 1 mm was
      identified to reliably detect in-stent neointima hyperplasia with MSCT.
      CONCLUSIONS: Current MSCT technology, in combination with optimal heart rate
      control, allows reliable noninvasive evaluation of selected patients after LMCA
      stenting. MSCT is safe to exclude left main ISR and may therefore be an
      acceptable first-line alternative to CCA.

PMID- 16894039
TI  - Orthostatic hypotension predicts mortality in middle-aged adults: the
      Atherosclerosis Risk In Communities (ARIC) Study.
AB  - BACKGROUND: An association between orthostatic hypotension (OH) and mortality has
      been reported, but studies are limited to older adults or high-risk populations.
      METHODS AND RESULTS: We investigated the association between OH (a decrease of 20
      mm Hg in systolic blood pressure or a decrease of 10 mm Hg in diastolic blood
      pressure on standing) and 13-year mortality among middle-aged black and white men
      and women from the Atherosclerosis Risk in Communities Study (1987-1989). At
      baseline, 674 participants (5%) had OH. All-cause mortality was higher among
      those with (13.7%) than without (4.2%) OH. After we controlled for ethnicity,
      gender, and age, the hazard ratio (HR) for OH for all-cause mortality was 2.4
      (95% confidence interval [CI], 2.1 to 2.8). Adjustment for risk factors for
      cardiovascular disease and mortality and selected health conditions at baseline
      attenuated but did not completely explain this association (HR = 1.7; 95% CI, 1.4
      to 2.0). This association persisted among subsets that (1) excluded those who
      died within the first 2 years of follow-up and (2) were limited to those without
      coronary heart disease, cancer, stroke, diabetes, hypertension, or fair/poor
      perceived health status at baseline. In analyses by causes of death, a
      significant increased hazard of death among those with versus without OH
      persisted after adjustment for risk factors for cardiovascular disease (HR = 2.0;
      95% CI, 1.6 to 2.7) and other deaths (HR = 2.1; 95% CI, 1.6 to 2.8) but not for
      cancer (odds ratio = 1.1; 95% CI, 0.8 to 1.6). CONCLUSIONS: OH predicts mortality
      in middle-aged adults. This association is only partly explained by traditional
      risk factors for cardiovascular disease and overall mortality.

PMID- 16894040
TI  - Plaque volume and occurrence and location of periprocedural myocardial necrosis
      after percutaneous coronary intervention: insights from delayed-enhancement
      magnetic resonance imaging, thrombolysis in myocardial infarction myocardial
      perfusion grade analysis, and intravascular ultrasound.
AB  - BACKGROUND: Myocardial necrosis can occur during percutaneous coronary
      intervention (PCI) despite optimal adjunctive pharmacology and careful technique.
      We investigated the mechanisms of procedural infarction using angiographic
      analysis, intravascular ultrasound, and delayed-enhancement magnetic resonance
      imaging. METHODS AND RESULTS: Fifty-two patients (64 vessels) who underwent
      complex PCI were studied. All patients were preloaded with clopidogrel and
      received glycoprotein IIb/IIIa inhibitors. "Adjacent" myonecrosis was defined as
      the presence of an area of new gadolinium hyperenhancement close to the stent.
      "Distal" myonecrosis was defined as situated at least 10 mm downstream from the
      stent. Fifteen vessels (23%) had evidence of new hyperenhancement after PCI. Of
      these, 8 (12%) had the distal type, and 7 (11%) had the adjacent type.
      Intravascular ultrasound showed a significantly greater reduction in plaque
      volume (91.6+/-51.5 versus 8+/-14 versus 20+/-35 mm3; P < 0.001) in the group
      with distal hyperenhancement compared with patients without new hyperenhancement
      or adjacent hyperenhancement. In the entire sample, a significant correlation was
      seen between changes in plaque volume (rho = 0.58, P < 0.001) after PCI and the
      mass of new necrosis measured by magnetic resonance imaging. Thrombolysis in
      Myocardial Infarction perfusion grade assessment of a closed microvasculature
      after PCI carried an odds ratio of 8.0 (95% confidence interval, 1.4 to 46.1; P =
      0.02) for the occurrence of hyperenhancement, whereas side-branch occlusion was
      associated with an odds ratio of 16.2 (95% confidence interval, 2.6 to 102.5; P =
      0.03). However, a closed microvasculature was associated with distal
      hyperenhancement (P = 0.02), and side-branch occlusion was associated with
      adjacent hyperenhancement (P < 0.001). CONCLUSIONS: These data suggest that
      distal embolization of plaque material occurs in contemporary PCI of native
      coronary arteries. Efforts to minimize procedural necrosis may require careful
      review of side branch anatomy and/or use of distal protection during extensive
      coronary stenting.

PMID- 16894041
TI  - Images in cardiovascular medicine. Percutaneous transluminal angioplasty for
      treatment of critical hand ischemia.

PMID- 16894042
TI  - Images in cardiovascular medicine. Gastroesophageal reflux facilitates esophageal
      imaging during pulmonary vein ablation.

PMID- 16894043
TI  - Images in cardiovascular medicine. Hybrid cardiac single photon emission computed
      tomography/computed tomography imaging with myocardial perfusion single photon
      emission computed tomography and multidetector computed tomography coronary
      angiography for the assessment of unstable angina pectoris after coronary artery
      bypass grafting.

PMID- 16894044
TI  - Letter regarding article by Newby et al, "Long-term adherence to evidence-based
      secondary prevention therapies in coronary artery disease".

PMID- 16894045
TI  - Letter by Kielstein et al regarding article, "Renal function as a predictor of
      outcome in a broad spectrum of patients with heart failure".

PMID- 16894047
TI  - Human ventricular fibrillation: wandering wavelets, mother rotors, or both?

PMID- 16894048
TI  - The evolving treatment of aortic stenosis: do new procedures provide new
      treatment options for the highest-risk patients?

PMID- 16894049
TI  - Advanced glycation end products: sparking the development of diabetic vascular
      injury.
AB  - Advanced glycation end products (AGEs) are proteins or lipids that become
      glycated after exposure to sugars. AGEs are prevalent in the diabetic vasculature
      and contribute to the development of atherosclerosis. The presence and
      accumulation of AGEs in many different cell types affect extracellular and
      intracellular structure and function. AGEs contribute to a variety of
      microvascular and macrovascular complications through the formation of cross
      links between molecules in the basement membrane of the extracellular matrix and
      by engaging the receptor for advanced glycation end products (RAGE). Activation
      of RAGE by AGEs causes upregulation of the transcription factor nuclear factor
      kappaB and its target genes. Soluble AGEs activate monocytes, and AGEs in the
      basement membrane inhibit monocyte migration. AGE-bound RAGE increases
      endothelial permeability to macromolecules. AGEs block nitric oxide activity in
      the endothelium and cause the production of reactive oxygen species. Because of
      the emerging evidence about the adverse effects of AGEs on the vasculature of
      patients with diabetes, a number of different therapies to inhibit AGEs are under
      investigation.

PMID- 16894052
TI  - Surgical menopause, salt sensitivity, and NO bioavailability in women.

PMID- 16894050
TI  - New technology for surgical coronary revascularization.

PMID- 16894053
TI  - Superoxide stimulates NaCl absorption in the thick ascending limb via activation
      of protein kinase C.
AB  - Abnormal production of superoxide (O(2)(-)) contributes to hypertension, in part
      because of its effects on the kidney. The thick ascending limb absorbs 20% to 30%
      of the filtered load of NaCl. O(2)(-) stimulates NaCl absorption by the thick
      ascending limb by enhancing Na(+)/K(+)/2Cl(-) cotransporter activity; however,
      the signaling mechanism is unknown. We hypothesized that O(2)(-) stimulates NaCl
      absorption by activating protein kinase C (PKC). To test this, we measured the
      effect of O(2)(-) on: (1) Cl(-) absorption in the presence and absence of PKC
      inhibitors, (2) total PKC activity, and (3) activation of specific PKC isoforms.
      Isolated perfused medullary thick ascending limbs were exposed to O(2)(-)
      generated by xanthine oxidase (1 mU/mL) and hypoxanthine (0.5 mmol/L). O(2)(-)
      increased Cl(-) absorption by 42% (from 76.2+/-3.6 to 108.2+/-11.9 pmol/min per
      millimeter; n=5; P<0.05). After treatment with the general PKC inhibitor
      staurosporine (10 nmol/L), O(2)(-) did not stimulate Cl(-) absorption (Delta
      5.7+/-8.6%; n=6). In thick ascending limb suspensions, O(2)(-) increased total
      PKC activity by 33% (from 66+/-11 to 88+/-12 mU/mg protein; n=5; P<0.05) and
      increased PKC-alpha and PKC-delta activity by 1.75- and 0.37-fold, respectively.
      The PKC-alpha/beta-selective inhibitor Go976 (100 nmol/L) blocked the ability of
      O(2)(-) to stimulate Cl(-) absorption by isolated perfused medullary thick
      ascending limbs (Delta4.5+/-15.0%; n=5). The role of PKC-delta could not be
      studied because of cell necrosis caused by the selective inhibitor rottlerin. We
      conclude that PKC-alpha is required for O(2)(-)-stimulated NaCl absorption in the
      thick ascending limb.

PMID- 16894055
TI  - Amlodipine better than lisinopril? How one randomized clinical trial ended
      fallacies from observational studies.

PMID- 16894056
TI  - Does angiotensin receptor recycling regulate blood pressure?

PMID- 16894057
TI  - Extracellular superoxide dismutase depletion in hypertension unmasks a new role
      for angiotensin II in regulating Cu,Zn-superoxide dismutase activity.

PMID- 16894058
TI  - Nox2, Ca2+, and protein kinase C play a role in angiotensin II-induced free
      radical production in nucleus tractus solitarius.
AB  - The dorsomedial portion of the nucleus tractus solitarius (dmNTS) is the site of
      termination of baroreceptor and cardiorespiratory vagal afferents and plays a
      critical role in cardiovascular regulation. Angiotensin II (Ang II) is a powerful
      signaling molecule in dmNTS neurons and exerts some of its biological effects by
      modulating Ca(2+) currents via reactive oxygen species (ROS) derived from reduced
      nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase. We investigated
      whether a Nox2-containing NADPH oxidase is the source of the Ang II-induced ROS
      production and whether the signaling mechanisms of its activation require
      intracellular Ca(2+) or protein kinase C (PKC). Second-order dmNTS neurons were
      anterogradely labeled with 4-(4-[didecylamino]styryl)-N-methylpyridinium iodide
      transported from the vagus and isolated from the brain stem. ROS production was
      assessed in 4-(4-[didecylamino]styryl)-N-methylpyridinium iodide-positive dmNTS
      neurons using the fluorescent dye 6-carboxy-2',7'-dichlorodihydro-fluorescein
      di(acetoxymethyl ester). Ang II (3 to 2000 nmol/L) increased ROS production in
      dmNTS neurons (EC(50)=38.3 nmol/L). The effect was abolished by the ROS scavenger
      Mn (III) porphyrin 5,10,20-tetrakis (benzoic acid) porphyrin manganese (III), the
      Ang II type 1 receptor antagonist losartan, or the NADPH oxidase inhibitors
      apocynin or gp91ds-tat. Ang II failed to increase ROS production or to potentiate
      L-type Ca(2+) currents in dmNTS neurons of mice lacking Nox2. The PKC inhibitor
      GF109203X or depletion of intracellular Ca(2+) attenuated Ang II-elicited ROS
      production. We conclude that the powerful effects of Ang II on Ca(2+) currents in
      dmNTS neurons are mediated by PKC activation leading to ROS production via Nox2.
      Thus, a Nox2-containing NADPH oxidase is the critical link between Ang II and the
      enhancement of Ca(2+) currents that underlie the actions of Ang II on central
      autonomic regulation.

PMID- 16894059
TI  - Metropolis.

PMID- 16894060
TI  - Genetic association and brain morphology studies and the chromosome 8p22
      pericentriolar material 1 (PCM1) gene in susceptibility to schizophrenia.
AB  - CONTEXT: There is evidence of linkage to a schizophrenia susceptibility locus on
      chromosome 8p21-22 found by several family linkage studies. OBJECTIVES: To fine
      map and identify a susceptibility gene for schizophrenia on chromosome 8p22 and
      to investigate the effect of this genetic susceptibility on an endophenotype of
      abnormal brain structure using magnetic resonance imaging. DESIGN: Fine mapping
      and identification of a chromosome 8p22 susceptibility gene was carried out by
      finding linkage disequilibrium between genetic markers and schizophrenia in
      multiply affected families, a case-control sample, and a trio sample. Variation
      in brain morphology associated with pericentriolar material 1 (PCM1) alleles was
      examined using voxel-based morphometry and statistical parametric mapping with
      magnetic resonance imaging. Setting and Patients A family sample of 13 large
      families multiply affected with schizophrenia, 2 schizophrenia case-control
      samples from the United Kingdom and Scotland, and a sample of schizophrenic trios
      from the United States containing parents and 1 affected child with
      schizophrenia. MAIN OUTCOME MEASURES: Tests of transmission disequilibrium
      between PCM1 locus polymorphisms and schizophrenia using a family sample and
      tests of allelic association in case-control and trio samples. Voxel-based
      morphometry using statistical parametric mapping. RESULTS: The family and trio
      samples both showed significant transmission disequilibrium between marker D85261
      in the PCM1 gene locus and schizophrenia. The case-control sample from the United
      Kingdom also found significant allelic association between PCM1 gene markers and
      schizophrenia. Voxel-based morphometry of cases who had inherited a PCM1 genetic
      susceptibility showed a significant relative reduction in the volume of
      orbitofrontal cortex gray matter in comparison with patients with non-PCM1
      associated schizophrenia, who, by contrast, showed gray matter volume reduction
      in the temporal pole, hippocampus, and inferior temporal cortex. CONCLUSIONS: The
      PCM1 gene is implicated in susceptibility to schizophrenia and is associated with
      orbitofrontal gray matter volumetric deficits.

PMID- 16894061
TI  - A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant
      major depression.
AB  - CONTEXT: Existing therapies for major depression have a lag of onset of action of
      several weeks, resulting in considerable morbidity. Exploring pharmacological
      strategies that have rapid onset of antidepressant effects within a few days and
      that are sustained would have an enormous impact on patient care. Converging
      lines of evidence suggest the role of the glutamatergic system in the
      pathophysiology and treatment of mood disorders. OBJECTIVE: To determine whether
      a rapid antidepressant effect can be achieved with an antagonist at the N-methyl
      D-aspartate receptor in subjects with major depression. DESIGN: A randomized,
      placebo-controlled, double-blind crossover study from November 2004 to September
      2005. SETTING: Mood Disorders Research Unit at the National Institute of Mental
      Health. Patients Eighteen subjects with DSM-IV major depression (treatment
      resistant). INTERVENTIONS: After a 2-week drug-free period, subjects were given
      an intravenous infusion of either ketamine hydrochloride (0.5 mg/kg) or placebo
      on 2 test days, a week apart. Subjects were rated at baseline and at 40, 80, 110,
      and 230 minutes and 1, 2, 3, and 7 days postinfusion. Main Outcome Measure
      Changes in scores on the primary efficacy measure, the 21-item Hamilton
      Depression Rating Scale. RESULTS: Subjects receiving ketamine showed significant
      improvement in depression compared with subjects receiving placebo within 110
      minutes after injection, which remained significant throughout the following
      week. The effect size for the drug difference was very large (d = 1.46 [95%
      confidence interval, 0.91-2.01]) after 24 hours and moderate to large (d = 0.68
      [95% confidence interval, 0.13-1.23]) after 1 week. Of the 17 subjects treated
      with ketamine, 71% met response and 29% met remission criteria the day following
      ketamine infusion. Thirty-five percent of subjects maintained response for at
      least 1 week. CONCLUSIONS: Robust and rapid antidepressant effects resulted from
      a single intravenous dose of an N-methyl-D-aspartate antagonist; onset occurred
      within 2 hours postinfusion and continued to remain significant for 1 week.

PMID- 16894062
TI  - Antidepressant drug therapy and suicide in severely depressed children and
      adults: A case-control study.
AB  - CONTEXT: The Food and Drug Administration has issued a boxed warning concerning
      increased suicidal ideation and behavior associated with antidepressant drug
      treatment in children and adolescents. It is unknown whether antidepressant
      agents increase the risk of suicide death in children or adults. OBJECTIVE: To
      estimate the relative risk of suicide attempt and suicide death in severely
      depressed children and adults treated with antidepressant drugs vs those not
      treated with antidepressant drugs. DESIGN: Matched case-control study. SETTING:
      Outpatient treatment settings in the United States. PARTICIPANTS: Medicaid
      beneficiaries from all 50 states who received inpatient treatment for depression,
      excluding patients treated for pregnancy, bipolar disorder, schizophrenia or
      other psychoses, mental retardation, dementia, or delirium. Controls were matched
      to cases for age, sex, race or ethnicity, state of residence, substance use
      disorder, recent suicide attempt, number of days since hospital discharge, and
      recent treatment with antipsychotic, anxiolytic/hypnotic, mood stabilizer, and
      stimulant medications. MAIN OUTCOME MEASURES: Suicide attempts and suicide
      deaths. RESULTS: In adults (aged 19-64 years), antidepressant drug treatment was
      not significantly associated with suicide attempts (odds ratio [OR], 1.10; 95%
      confidence interval [CI], 0.86-1.39 [521 cases and 2394 controls]) or suicide
      deaths (OR, 0.90; 95% CI, 0.52-1.55 [86 cases and 396 controls]). However, in
      children and adolescents (aged 6-18 years), antidepressant drug treatment was
      significantly associated with suicide attempts (OR, 1.52; 95% CI, 1.12-2.07 [263
      cases and 1241 controls]) and suicide deaths (OR, 15.62; 95% CI, 1.65-infinity [8
      cases and 39 controls]). CONCLUSIONS: In these high-risk patients, antidepressant
      drug treatment does not seem to be related to suicide attempts and death in
      adults but might be related in children and adolescents. These findings support
      careful clinical monitoring during antidepressant drug treatment of severely
      depressed young people.

PMID- 16894063
TI  - Depression symptom severity and reported treatment history in the prediction of
      cardiac risk in women with suspected myocardial ischemia: The NHLBI-sponsored
      WISE study.
AB  - BACKGROUND: Depression is associated with clinical events and premature mortality
      among patients with established coronary artery disease (CAD). Typically,
      however, studies in this area focus only on baseline symptom severity and lack
      any data concerning symptom duration or symptom history. OBJECTIVES: To describe
      and compare the relationships between 2 measures of depression-assessed in the
      form of depression symptom severity and reported treatment history-with
      atherosclerosis risk factors and major clinical events in a sample of women with
      suspected myocardial ischemia. DESIGN: Follow-up study of women who completed a
      diagnostic CAD protocol, including cardiac symptoms, coronary angiography,
      ischemic testing, and assessments of depression symptom severity and reported
      treatment history. SETTING: The Women's Ischemia Syndrome Evaluation (WISE), a
      National Heart, Lung, and Blood Institute (NHLBI)-sponsored multicenter study
      assessing cardiovascular function using state-of-the-art techniques in women
      referred for coronary angiography to evaluate chest pain or suspected myocardial
      ischemia. PARTICIPANTS: Five hundred five women (mean age, 53.4 years) enrolled
      in WISE and followed up for a mean of 4.9 years. MAIN OUTCOME MEASURES: Incidence
      of cardiac events, including myocardial infarction, stroke, and heart failure,
      and total mortality. RESULTS: Relative to those with no or less stable depression
      symptoms, women with elevated depression symptoms and a reported treatment
      history showed higher rates of smoking, hypertension, and poorer education and an
      increased incidence of death and cardiac events (multivariate-adjusted risk
      ratio, 3.1; 95% confidence interval, 1.5-6.3; P = .001). CONCLUSIONS: Among women
      with suspected myocardial ischemia, a combination of depressive symptom severity
      and treatment history was a strong predictor of an elevated CAD risk profile and
      increased risk of cardiac events compared with those without depression or with
      only 1 of the 2 measured depression markers. These findings reinforce the
      importance of assessing mental health factors in women at elevated CAD risk.
      Focusing only on baseline depression symptom severity may provide an incomplete
      picture of CAD risk.

PMID- 16894064
TI  - Prevention of eating disorders in at-risk college-age women.
AB  - CONTEXT: Eating disorders, an important health problem among college-age women,
      may be preventable, given that modifiable risk factors for eating disorders have
      been identified and interventions have been evaluated to reduce these risk
      factors. OBJECTIVE: To determine if an Internet-based psychosocial intervention
      can prevent the onset of eating disorders (EDs) in young women at risk for
      developing EDs. SETTING: San Diego and the San Francisco Bay Area in California.
      PARTICIPANTS: College-age women with high weight and shape concerns were
      recruited via campus e-mails, posters, and mass media. Six hundred thirty-seven
      eligible participants were identified, of whom 157 were excluded, for a total
      sample of 480. Recruitment occurred between November 13, 2000, and October 10,
      2003. Intervention A randomized controlled trial of an 8-week, Internet-based
      cognitive-behavioral intervention (Student Bodies) that included a moderated
      online discussion group. Participants were studied for up to 3 years. MAIN
      OUTCOME MEASURES: The main outcome measure was time to onset of a subclinical or
      clinical ED. Secondary measures included change in scores on the Weight Concerns
      Scale, Global Eating Disorder Examination Questionnaire, and Eating Disorder
      Inventory drive for thinness and bulimia subscales and depressed mood. Moderators
      of outcome were examined. RESULTS: There was a significant reduction in Weight
      Concerns Scale scores in the Student Bodies intervention group compared with the
      control group at postintervention (P < .001), 1 year (P < .001), and 2 years (P <
      .001). The slope for reducing Weight Concerns Scale score was significantly
      greater in the treatment compared with the control group (P = .02). Over the
      course of follow-up, 43 participants developed subclinical or clinical EDs. While
      there was no overall significant difference in onset of EDs between the
      intervention and control groups, the intervention significantly reduced the onset
      of EDs in 2 subgroups identified through moderator analyses: (1) participants
      with an elevated body mass index (BMI) (> or =25, calculated as weight in
      kilograms divided by height in meters squared) at baseline and (2) at 1 site,
      participants with baseline compensatory behaviors (eg, self-induced vomiting,
      laxative use, diuretic use, diet pill use, driven exercise). No intervention
      participant with an elevated baseline BMI developed an ED, while the rates of
      onset of ED in the comparable BMI control group (based on survival analysis) were
      4.7% at 1 year and 11.9% at 2 years. In the subgroup with a BMI of 25 or higher,
      the cumulative survival incidence was significantly lower at 2 years for the
      intervention compared with the control group (95% confidence interval, 0% for
      intervention group; 2.7% to 21.1% for control group). For the San Francisco Bay
      Area site sample with baseline compensatory behaviors, 4% of participants in the
      intervention group developed EDs at 1 year and 14.4%, by 2 years. Rates for the
      comparable control group were 16% and 30.4%, respectively. CONCLUSIONS: Among
      college-age women with high weight and shape concerns, an 8-week, Internet-based
      cognitive-behavioral intervention can significantly reduce weight and shape
      concerns for up to 2 years and decrease risk for the onset of EDs, at least in
      some high-risk groups. To our knowledge, this is the first study to show that EDs
      can be prevented in high-risk groups.

PMID- 16894065
TI  - Timing of menarche and the origins of conduct disorder.
AB  - CONTEXT: Precocious onset of menses (ie, age < or =11 years) has repeatedly been
      identified as a risk factor for higher rates of delinquency or conduct disorder
      (CD) in girls. Although this association is often conceptualized as
      environmentally mediated (via processes such as affiliation of early-menstruating
      youth with older, more deviant peers), such conclusions are premature as
      biological and genetic explanations have yet to be fully considered. OBJECTIVE:
      To uncover the origins of the association between CD and timing of menarche.
      DESIGN, SETTING, AND PARTICIPANTS: The sample consisted of a population-based
      birth cohort of 708 mid-adolescent female twins assessed as part of the ongoing
      Minnesota Twin Family Study. We conducted 2 sets of analyses: standard bivariate
      analyses to uncover possible common genes and moderator analyses to evaluate
      possible moderation of genetic influences on CD by timing of menarche. MAIN
      OUTCOME MEASURES: Conduct disorder was assessed via individual semistructured
      interviews with mothers and adolescents. Menarcheal status and age at menarche
      were assessed via the Pubertal Development Scale. RESULTS: The results argued
      against common genetic influences but did provide evidence of etiological
      moderation of CD by timing of menarche. The heritability of CD was strongest
      (67%) in girls with average timing of menarche (ie, age 12-13 years) and
      substantially weaker (8%) in those with early onset. Those with late initiation
      of menses (ie, age >13 years) similarly exhibited weaker genetic influences
      (29%). Shared environmental influences showed the opposite pattern, as they were
      far stronger for those with precocious and delayed onset vs those with average
      onset. CONCLUSIONS: Our findings provide indirect support for psychosocial
      interpretations of the impact of precocious menarche and, to a lesser extent,
      delayed menarche on CD development. Further, they lend support to the notion that
      in some cases, genetic influences on psychopathology may be strongest in the
      "average, expectable" environment.

PMID- 16894066
TI  - Neonatal outcomes after prenatal exposure to selective serotonin reuptake
      inhibitor antidepressants and maternal depression using population-based linked
      health data.
AB  - CONTEXT: Prenatal exposure to selective serotonin reuptake inhibitor (SSRI)
      antidepressants and maternal depression both alter neonatal health, and
      distinguishing the effects of each influence remains challenging. OBJECTIVE: To
      determine whether exposure to SSRIs and depression differs from exposure to
      maternal depression alone. DESIGN: Using population health data, records of
      neonatal birth outcomes were linked to records of maternal health and prenatal
      maternal prescriptions for SSRIs. SETTING: Population of British Columbia,
      Canada. PARTICIPANTS: Mothers and their infants, representing all live births
      during a 39-month period (N = 119,547) (1998-2001). MAIN OUTCOME MEASURES:
      Outcomes from infants of depressed mothers treated with SSRIs (SE-D) were
      compared with outcomes from infants of depressed mothers not treated with
      medication (DE) and nonexposed controls. To control for maternal mental illness
      severity, propensity score matching was used to identify a comparison group of DE
      mothers who were similar to the SE-D mothers in characteristics in the year
      preceding and during pregnancy. RESULTS: Fourteen percent of mothers were
      diagnosed as having depression during their pregnancy, and the incidence of
      prenatal SSRI exposure increased from 2.3% to 5.0% during a 39-month period.
      Birth weight and gestational age for SE-D infants were significantly less than
      for DE infants, as was the proportion of infants born at less than 37 weeks (95%
      confidence interval [CI], -1 to -64, -0.25 to -0.45, and -0.009 to -0.04,
      respectively), although differences in the incidence of birth weight less than
      the 10th percentile for gestational age were not significant. An increased
      proportion of SE-D infants had neonatal respiratory distress (13.9% vs 7.8%),
      jaundice (9.4% vs 7.5%), and feeding problems (3.9% vs 2.4%) compared with DE
      infants (95% CI of difference, 0.042-0.079, 0.003-0.334, and 0.005-0.025,
      respectively). When outcomes were compared between SE-D and propensity score
      matched DE neonates, SE-D was associated with increased incidence of birth weight
      below the 10th percentile and rates of respiratory distress. CONCLUSION: With
      linked population health data and propensity score matching, prenatal SE-D
      exposure was associated with an increased risk of low birth weight and
      respiratory distress, even when maternal illness severity was accounted for.

PMID- 16894067
TI  - Cigarette smoking saturates brain alpha 4 beta 2 nicotinic acetylcholine
      receptors.
AB  - CONTEXT: 2-[18F]fluoro-3-(2(S)-azetidinylmethoxy) pyridine (2-F-A-85380,
      abbreviated as 2-FA) is a recently developed radioligand that allows for
      visualization of brain alpha 4 beta 2* nicotinic acetylcholine receptors (nAChRs)
      with positron emission tomography (PET) scanning in humans. OBJECTIVE: To
      determine the effect of cigarette smoking on alpha 4 beta 2* nAChR occupancy in
      tobacco-dependent smokers. DESIGN: Fourteen 2-FA PET scanning sessions were
      performed. During the PET scanning sessions, subjects smoked 1 of 5 amounts
      (none, 1 puff, 3 puffs, 1 full cigarette, or to satiety [2(1/2) to 3
      cigarettes]). SETTING: Academic brain imaging center. PARTICIPANTS: Eleven
      tobacco-dependent smokers (paid volunteers). Main Outcome Measure Dose-dependent
      effect of smoking on occupancy of alpha 4 beta 2* nAChRs, as measured with 2-FA
      and PET in nAChR-rich brain regions. RESULTS: Smoking 0.13 (1 to 2 puffs) of a
      cigarette resulted in 50% occupancy of alpha 4 beta 2* nAChRs for 3.1 hours after
      smoking. Smoking a full cigarette (or more) resulted in more than 88% receptor
      occupancy and was accompanied by a reduction in cigarette craving. A venous
      plasma nicotine concentration of 0.87 ng/mL (roughly 1/25th of the level achieved
      in typical daily smokers) was associated with 50% occupancy of alpha 4 beta 2*
      nAChRs. CONCLUSIONS: Cigarette smoking in amounts used by typical daily smokers
      leads to nearly complete occupancy of alpha 4 beta 2* nAChRs, indicating that
      tobacco-dependent smokers maintain alpha 4 beta 2* nAChR saturation throughout
      the day. Because prolonged binding of nicotine to alpha 4 beta 2* nAChRs is
      associated with desensitization of these receptors, the extent of receptor
      occupancy found herein suggests that smoking may lead to withdrawal alleviation
      by maintaining nAChRs in the desensitized state.

PMID- 16894068
TI  - Neuropsychological prediction of conversion to Alzheimer disease in patients with
      mild cognitive impairment.
AB  - CONTEXT: The likelihood of conversion to Alzheimer disease (AD) in mild cognitive
      impairment (MCI) and the "optimal" early markers of conversion need to be
      established. OBJECTIVES: To evaluate conversion rates to AD in subtypes of MCI
      and to identify neuropsychological measures most predictive of the time to
      conversion. DESIGN: Patients were followed up semiannually and controls annually.
      Subtypes of MCI were determined by using demographically adjusted regression
      norms on neuropsychological tests. Survival analysis was used to identify the
      most predictive neuropsychological measures. SETTING: Memory disorders clinic.
      PARTICIPANTS: One hundred forty-eight patients reporting memory problems and 63
      group-matched controls. MAIN OUTCOME MEASURE: A consensus diagnosis of probable
      AD. RESULTS: At baseline, 108 patients met criteria for amnestic MCI: 87 had
      memory plus other cognitive domain deficits and 21 had pure memory deficits. The
      mean duration of follow-up for the 148 patients was 46.6 +/- 24.6 months. In 3
      years, 32 (50.0%) of 64 amnestic-"plus" and 2 (10.0%) of 20 "pure" amnestic
      patients converted to AD (P = .001). In 148 patients, of 5 a priori predictors,
      the percent savings from immediate to delayed recall on the Selective Reminding
      Test and the Wechsler Adult Intelligence Scale-Revised Digit Symbol Test were the
      strongest predictors of time to conversion. From the entire neuropsychological
      test battery, a stepwise selection procedure retained 2 measures in the final
      model: total immediate recall on the Selective Reminding Test (odds ratio per 1
      point decrease, 1.10; 95% confidence interval, 1.05-1.14; P < .0001) and Digit
      Symbol Test coding (odds ratio, 1.06; 95% confidence interval, 1.01-1.11; P =
      .01). The combined predictive accuracy of these 2 measures for conversion by 3
      years was 86%. CONCLUSIONS: Mild cognitively impaired patients with memory plus
      other cognitive domain deficits, rather than those with pure amnestic MCI,
      constituted the high-risk group. Deficits in verbal memory and psychomotor
      speed/executive function abilities strongly predicted conversion to AD.

PMID- 16894070
TI  - Subjecting meta-analyses to closer scrutiny: Little support for differential
      efficacy among second-generation antipsychotics at equivalent doses.

PMID- 16894069
TI  - National survey of psychotherapy training in psychiatry, psychology, and social
      work.
AB  - CONTEXT: Approximately 3% of the US population receives psychotherapy each year
      from psychiatrists, psychologists, or social workers. A modest number of
      psychotherapies are evidence-based therapy (EBT) in that they have been defined
      in manuals and found efficacious in at least 2 controlled clinical trials with
      random assignment that include a control condition of psychotherapy, placebo,
      pill, or other treatment and samples of sufficient power with well-characterized
      patients. Few practitioners use EBT. OBJECTIVE: To determine the amount of EBT
      taught in accredited training programs in psychiatry, psychology (PhD and PsyD),
      and social work and to note whether the training was elective or required and
      presented as a didactic (coursework) or clinical supervision. DESIGN, SETTING,
      AND PARTICIPANTS: A cross-sectional survey of a probability sample of all
      accredited training programs in psychiatry, psychology, and social work in the
      United States. Responders included training directors (or their designates) from
      221 programs (73 in psychiatry, 63 in PhD clinical psychology, 21 in PsyD
      psychology, and 64 in master's-level social work). The overall response rate was
      73.7%. Main Outcome Measure Requiring both a didactic and clinical supervision in
      an EBT. RESULTS: Although programs offered electives in EBT and non-EBT, few
      required both a didactic and clinical supervision in EBT, and most required
      training was non-EBT. Psychiatry required coursework and clinical supervision in
      the largest percentage of EBT (28.1%). Cognitive behavioral therapy was the EBT
      most frequently offered and required as a didactic in all 3 disciplines. More
      than 90% of the psychiatry training programs were complying with the new
      cognitive behavior therapy requirement. The 2 disciplines with the largest number
      of students and emphasis on clinical training-professional clinical psychology
      (PsyD) and social work-had the largest percentage of programs (67.3% and 61.7%,
      respectively) not requiring a didactic and clinical supervision in any EBT.
      CONCLUSION: There is a considerable gap between research evidence for
      psychotherapy and clinical training. Until the training programs in the major
      disciplines providing psychotherapy increase training in EBT, the gap between
      research evidence and clinical practice will remain.

PMID- 16894071
TI  - Estimation of haplotypes at DRD2 may have produced misleading results.

PMID- 16894072
TI  - Distinguishing current from remitted posttraumatic stress disorder.

PMID- 16894073
TI  - Beginnings and endings.

PMID- 16894075
TI  - Risk factors for opportunistic illnesses in children with human immunodeficiency
      virus in the era of highly active antiretroviral therapy.
AB  - OBJECTIVE: To examine the relationship between the use of highly active
      antiretroviral treatment (HAART) and the occurrence of opportunistic illnesses
      (OIs) among children perinatally infected with human immunodeficiency virus.
      DESIGN: Prospective cohort study. SETTING: Pediatric AIDS Clinical Trials Group
      219C cohort. PARTICIPANTS: From September 15, 2000, to August 31, 2003, 1927
      children perinatally infected with human immunodeficiency virus and receiving
      HAART were followed up. Main Exposures Age at initiating HAART, duration of HAART
      use, CD4+ T-lymphocyte percentage, and human immunodeficiency virus 1 viral load.
      MAIN OUTCOME MEASURES: Incidence rates for Centers for Disease Control and
      Prevention OI category B and OI category C events were calculated. The
      association between main exposures and OI occurrence was estimated using
      proportional hazards regression. RESULTS: Of 1927 subjects, 226 (12.7%) developed
      OIs during follow-up. Incidence rates were 4.99 per 100 person-years (95%
      confidence interval, 4.30-5.76) for first OI category B events and 1.47 per 100
      person-years (95% confidence interval, 1.12-1.91) for first OI category C events.
      Duration of HAART use was not related to OI risk. Older age (age >10 years) at
      HAART initiation was associated with increased risk of a first OI (hazard ratio,
      2.48; 95% confidence interval, 1.23-5.00) compared with initiating HAART in
      children younger than 2 years. This increased risk diminished after adjusting for
      CD4+ T-lymphocyte percentage and Centers for Disease Control and Prevention
      disease category at HAART initiation. More children with OIs than without OIs had
      a CD4+ T-lymphocyte percentage of less than 15% at HAART initiation (49.6% of
      children with OIs vs 23.7% of children without OIs), at enrollment (41.2% of
      children with OIs vs 7.7% of children without OIs), and at the end of follow-up
      (41.2% of children with OIs vs 8.3% of children without OIs). CONCLUSIONS:
      Opportunistic illnesses are occurring in the pediatric human immunodeficiency
      virus population in the HAART era, mainly in children with persistently low CD4+
      T-lymphocyte percentages. Lack of a sustained response to HAART rather than age
      at or duration of HAART use is predictive of OI risk.

PMID- 16894074
TI  - A randomized controlled trial testing an HIV prevention intervention for Latino
      youth.
AB  - OBJECTIVE: To test the efficacy of a prevention intervention to reduce sexual
      risk behavior among Latino adolescents. DESIGN: Randomized controlled trial from
      April 2000 through March 2003, with data collection before and after intervention
      and at 3, 6, and 12 months. SETTING: Northeast Philadelphia schools.
      PARTICIPANTS: Latinos aged 13 through 18 years (249 males and 304 females); 81.6%
      retained at 12-month follow-up. INTERVENTIONS: The HIV and health-promotion
      control interventions consisted of six 50-minute modules delivered by adult
      facilitators to small, mixed-gender groups in English or Spanish. Main Outcome
      Measure Self-reported sexual behavior. RESULTS: Analyses using generalized
      estimation equations over the follow-up period revealed that adolescents in the
      HIV intervention were less likely to report sexual intercourse (odds ratio, 0.66;
      95% confidence interval [CI], 0.46-0.96), multiple partners (odds ratio, 0.53;
      95% CI, 0.31-0.90), and days of unprotected intercourse (relative risk, 0.47; 95%
      CI, 0.26-0.84) and more likely to report using condoms consistently (odds ratio,
      1.91; 95% CI, 1.24-2.93). Baseline sexual experience and language use moderated
      intervention efficacy. Adolescents assigned to the HIV intervention who were
      sexually inexperienced at baseline reported fewer days of unprotected sex
      (relative risk, 0.22; 95% CI, 0.08-0.63); Spanish speakers were more likely to
      have used a condom at last intercourse (odds ratio, 4.73; 95% CI, 1.72-12.97) and
      had a greater proportion of protected sex (mean difference, 0.35; P<.01) compared
      with similar adolescents in the health-promotion intervention. CONCLUSION:
      Results provide evidence for the efficacy of HIV intervention in decreasing
      sexual activity and increasing condom use among Latino adolescents.

PMID- 16894077
TI  - Healthy steps in an integrated delivery system: child and parent outcomes at 30
      months.
AB  - OBJECTIVE: To test the effects of the Healthy Steps for Young Children program
      (HS) (which supports parents managing children's developmental and behavioral
      issues)-with and without a prenatal component-on child health and development,
      parenting practices, and parental well-being. DESIGN: A concurrent comparison
      with clinic-level assignment to intervention or usual care status. Nested in the
      intervention arm, a randomized trial compared HS with and without a prenatal
      component. SETTING: Five primary care clinics in an integrated delivery system in
      the Pacific Northwest. PARTICIPANTS: A consecutive sample of 439 pregnant women
      (80% of eligible) were enrolled. Follow-up data were obtained for 78% when the
      child was 30 months old. Intervention Families in intervention clinics received
      HS services, including developmental and behavioral advice and risk factor
      screening. In addition, those randomized to prenatal services received 3 home
      visits during pregnancy. MAIN OUTCOME MEASURES: Assessed by telephone interview
      in the 3 domains of child health and development, parenting practices, and
      parental well-being. RESULTS: Intervention was associated with positive outcomes
      in timely well-child care, immunization rates, breastfeeding, television viewing,
      injury prevention, and discipline strategies. Prenatal initiation of services was
      associated with larger expressive vocabularies at age 24 months. Mothers who
      received the intervention reported more depressive symptoms, but there was no
      increase in the proportion with clinically significant depression. CONCLUSIONS:
      For members of an integrated delivery system, the HS intervention was associated
      with positive effects on children's health and parenting practices. There was
      little evidence of any additional benefit of HS services initiated during the
      prenatal period.

PMID- 16894076
TI  - Are household firearms stored less safely in homes with adolescents?: Analysis of
      a national random sample of parents.
AB  - OBJECTIVE: To examine whether firearms are more frequently stored loaded,
      unlocked, or both in households with adolescents only (aged 13-17 years) compared
      with households with younger children only (aged 0-12 years). DESIGN: Random
      digit-dial survey on firearms (n = 2770). We computed bivariate associations
      between the presence of adolescents and firearm storage practices. Statistical
      significance was assessed using prevalence ratios with 95% confidence intervals.
      SETTING: United States. PARTICIPANTS: Survey respondents with children (aged <18
      years) who reported the presence of a household firearm. MAIN OUTCOME MEASURES:
      Prevalence of firearms in the home stored loaded and/or unlocked. RESULTS: Of the
      392 respondents, 22% had a loaded firearm, 32% had an unlocked firearm, and 8%
      had a firearm stored loaded and unlocked. Compared with households with younger
      children, households with adolescents only were somewhat more likely to store a
      firearm unlocked (42% vs 29%; prevalence ratio, 1.48; 95% confidence interval,
      1.04-2.02), loaded (26% vs 20%; prevalence ratio, 1.25; 95% confidence interval,
      0.82-1.91), or both (10% vs 8%; prevalence ratio, 1.43; 95% confidence interval,
      0.64-3.19). CONCLUSIONS: Parents of adolescents appear to be more likely to keep
      household firearms stored unsafely, especially with regard to keeping firearms
      unlocked. This is of concern because most youth firearm injuries happen to
      adolescents. Firearm injury prevention programs should directly target parents of
      adolescents to promote safe firearm storage.

PMID- 16894078
TI  - Picture of the month. Stevens-Johnson Syndrome.

PMID- 16894079
TI  - Socially isolated children 20 years later: risk of cardiovascular disease.
AB  - OBJECTIVE: To test the hypothesis that children who occupy peripheral or isolated
      roles in their peer groups (isolated children) are at risk of poor adult health.
      DESIGN: Longitudinal study of an entire birth cohort. SETTING: Dunedin, New
      Zealand. PARTICIPANTS: A total of 1037 children who were followed up from birth
      to age 26 years. INTERVENTIONS: Measurement of social isolation in childhood,
      adolescence, and adulthood. MAIN OUTCOME MEASURES: When study members were 26
      years old, we measured adult cardiovascular multifactorial risk status
      (overweight, elevated blood pressure, elevated total cholesterol level, low high
      density lipoprotein level, elevated glycated hemoglobin concentration, and low
      maximum oxygen consumption). RESULTS: Socially isolated children were at
      significant risk of poor adult health compared with nonisolated children (risk
      ratio, 1.37; 95% confidence interval, 1.17-1.61). This association was
      independent of other well-established childhood risk factors for poor adult
      health (low childhood socioeconomic status, low childhood IQ, childhood
      overweight), was not accounted for by health-damaging behaviors (lack of
      exercise, smoking, alcohol misuse), and was not attributable to greater exposure
      to stressful life events. In addition, longitudinal findings showed that chronic
      social isolation across multiple developmental periods had a cumulative, dose
      response relationship to poor adult health (risk ratio, 2.58; 95% confidence
      interval, 1.46-4.56). CONCLUSIONS: Longitudinal findings about children followed
      up to adulthood suggest that social isolation has persistent and cumulative
      detrimental effects on adult health. The findings underscore the usefulness of a
      life-course approach to health research, by focusing attention on the effect of
      the timing of psychosocial risk factors in relation to adult health.

PMID- 16894080
TI  - Association between severity of musculoskeletal injury and risk of subsequent
      injury in children and adolescents on the basis of parental recall.
AB  - OBJECTIVES: To describe the frequency of subsequent injuries in children who were
      seen at an emergency department (ED) for a musculoskeletal injury and to explore
      factors associated with sustaining a subsequent injury within a year. DESIGN:
      This was a prospective cohort study of children aged 1 through 17 years who
      sought care at an ED for an injury. Subsequent injuries were assessed through
      telephone interviews. SETTING: Subjects were recruited from a national database
      of childhood injury after they presented to a hospital ED at 1 of the 2 pediatric
      trauma centers in Montreal, Quebec. PATIENTS/ PARTICIPANTS: A consecutive sample
      of 7640 children aged 1 through 17 years who sought care for a fracture or a soft
      tissue injury to an arm or a leg; 6182 completed both telephone interviews (80.9%
      response rate). Main Exposure Having a more severe injury was defined in 2 ways:
      (1) fracture of a limb or (2) injury that required follow-up or admission. Main
      Outcome Measure Having a subsequent injury during 12-month follow-up. RESULTS:
      Subjects with an index fracture were at lower risk of subsequent injury than were
      those with a soft-tissue injury (13.5% compared with 17.7%; adjusted odds ratio,
      0.74; 95% confidence interval, 0.63-0.87). Subjects whose injury needed a follow
      up were also at lower risk of subsequent injury than those whose injury was
      treated only in the ED (17.7% compared with 14.3%; adjusted odds ratio, 0.79; 95%
      confidence interval, 0.67-0.93) as were those who were admitted (17.7% compared
      with 8.7%; adjusted odds ratio, 0.51; 95% confidence interval, 0.26-0.99).
      CONCLUSIONS: Having had a severe musculoskeletal injury may be associated with a
      decreased risk of subsequent injury in children and adolescents. A possible
      explanation could be reduced exposure to risk.

PMID- 16894082
TI  - Parental report of health conditions and health care use among children with and
      without autism: National Survey of Children's Health.
AB  - OBJECTIVE: To compare parent-reported prevalence of health conditions and health
      care use between children with and without autism. DESIGN: Cross-sectional
      analysis of the 2003 to 2004 National Survey of Children's Health. SETTING:
      Population-based sample across the United States. PARTICIPANTS: More than 100 000
      parents. The main exposure was "autism" (not further defined), from response to
      the question: "Has a doctor or health professional ever told you that your child
      has autism?" MAIN OUTCOME MEASURES: Medical and mental health conditions and
      measures of health care use. RESULTS: Autism prevalence among children aged 3 to
      17 years was 53 per 10 000 (95% confidence interval, 45-61 per 10,000), equating
      to a national estimate of 324 000 children (95% confidence interval, 274,000
      375,000 children). Children with autism had a significantly (P<.001) higher
      prevalence of depression or anxiety problems (38.9% vs 4.2%) and behavioral or
      conduct problems (58.9% vs 5.2%) than children without autism. Respiratory, food,
      and skin allergies were reported by parents more often for children with autism,
      with food allergies having the strongest relative difference between the groups
      (odds ratio, 4.5; 95% confidence interval, 3.0-7.0). Children with autism had
      significantly (P<.001) higher mean physician visits over 12 months for preventive
      care, nonemergency care, and hospital emergency care, and were far more likely
      than children without autism to receive physical, occupational, or speech therapy
      (76.0% vs 6.3%), to need treatment or counseling for an emotional, developmental,
      or behavioral problem (75.4% vs 7.0%), and, among those taking a prescribed
      medication, to be using a medication long-term (51.4% vs 14.5%). CONCLUSION: We
      found markedly higher reports of concurrent conditions and health care use
      associated with childhood autism in this study.

PMID- 16894081
TI  - Psychotropic medication use in pediatric patients with cancer.
AB  - BACKGROUND: Use of psychotropic medication in medically ill adults, in
      particular, patients with cancer, is common. While increased use of psychotropic
      medications in children and adolescents in the general population has been
      reported, little is known about the prescribing practices for these medications
      in medically ill children. OBJECTIVE: To examine the frequency and types of
      psychotropic medications used in a population of children and adolescents with
      cancer. DESIGN: Retrospective review of the National Institutes of Health Medical
      Information System. SETTING: Pediatric Oncology Branch of the National Cancer
      Institute, National Institutes of Health. PARTICIPANTS: Three hundred forty-seven
      patients aged 1 to 21 years who were enrolled in clinical research trials at the
      Pediatric Oncology Branch between January 2000 and December 2003. MAIN OUTCOME
      MEASURES: Psychotropic medication use was analyzed according to cancer diagnosis
      and patient age. RESULTS: Fourteen percent of identified patients had been
      prescribed at least 1 psychotropic medication at the time of National Cancer
      Institute clinical trial enrollment. The most commonly used medications were
      anticonvulsant agents (8%) and antidepressant medications (7%), in particular,
      selective serotonin reuptake inhibitors. Anxiolytic medications could not be
      accurately assessed because of their frequent use as antiemetic agents in many
      chemotherapy regimens. Psychostimulant use was rare. CONCLUSIONS: This study
      suggests that psychotropic medications are commonly prescribed to children and
      adolescents with cancer. Clinical safety and efficacy trials are needed in
      medically ill children at high risk for mood and anxiety symptoms.

PMID- 16894084
TI  - Assessment of immunization registry databases as supplemental sources of data to
      improve ascertainment of vaccination coverage estimates in the national
      immunization survey.
AB  - OBJECTIVE: To evaluate the use of immunization registry data to supplement
      missing or incomplete vaccination data reported by immunization providers
      (referred to as "providers" hereafter) in the National Immunization Survey.
      DESIGN: Cross-sectional, random-digit-dialing, telephone survey to measure
      vaccination coverage among children aged 19 to 35 months in the United States.
      SETTING: Four sites with mature (with >67% of provider participation in the area)
      immunization registries. PARTICIPANTS: Of the 639 children with complete
      household interviews, interviewers had consent from the respondents for 569
      (89.0%) children to contact their providers and for 556 (87.0%) children to
      contact both providers and registries. MAIN OUTCOME MEASURES: Percentages of
      children up-to-date for vaccines based on data from providers, registries, and
      both sources combined. RESULTS: According to provider-reported data, weighted
      estimates of coverage for the recommended childhood vaccine series 4:3:1:3 at the
      4 sites were 65.6%, 78.8%, 81.6%, and 77.0%. According to registry data, these
      coverage rates were consistently lower: 31.7% (P<.05), 65.4%, 71.9%, and 61.8%,
      respectively. When all unique vaccine doses were combined from both sources, the
      pooled 4:3:1:3 coverage rates increased to 72.0%, 92.0%, 88.7%, and 80.2%,
      respectively. The quality and completeness of vaccination histories from the
      registries were inconsistent and varied by sites. CONCLUSIONS: Vaccination
      coverage estimates were the lowest when only registry-reported data were used and
      were the highest when provider- and registry-reported histories were combined.
      Although registries enrolled and matched more children, vaccination histories
      were missing, incomplete, and inconsistent. The quality and completeness of the
      registry data must be improved and must be comparable across all states before
      further consideration may be given to supplement or replace the provider-reported
      National Immunization Survey data.

PMID- 16894083
TI  - Impact of staffing on bloodstream infections in the neonatal intensive care unit.
AB  - OBJECTIVE: To examine the association between registered nurse staffing and
      healthcare-associated bloodstream infections in infants in the neonatal intensive
      care unit (NICU). DESIGN: Prospective cohort study. SETTING: Two level III-IV
      NICUs in New York, NY, from March 1, 2001, through January 31, 2003.
      PARTICIPANTS: A total of 2675 infants admitted to the NICUs for more than 48
      hours and all registered nurses who worked in the same NICUs during the study
      period. Intervention Hours of care provided by registered nurses. Main Outcome
      Measure Time to first episode of healthcare-associated bloodstream infection.
      RESULTS: A total of 224 infants had an infection that met the study definition of
      healthcare-associated bloodstream infection. In a multivariate analysis, after
      controlling for infants' intrinsic and extrinsic risk factors, a greater number
      of hours of care provided by registered nurses in NICU 2 was associated with a
      decreased risk of bloodstream infection in these infants (hazard ratio, 0.21; 95%
      confidence interval, 0.06-0.79). CONCLUSION: Our findings suggest that registered
      nurse staffing is associated with the risk of bloodstream infection in infants in
      the NICU.

PMID- 16894086
TI  - Use of a partially hydrolyzed formula in the dietary prevention of allergic
      disease.

PMID- 16894085
TI  - Classification of asthma severity in children: the contribution of pulmonary
      function testing.
AB  - BACKGROUND: Despite increasing awareness of the National Asthma Education and
      Prevention Program guidelines, the relative contribution of symptom frequency or
      pulmonary function to the recommended asthma severity levels remains poorly
      understood. OBJECTIVE: To determine whether adding lung function measurements to
      clinical history substantially changes the asthma severity classification,
      thereby influencing treatment decisions. DESIGN: Baseline data were studied from
      children enrolled in 2 multicenter studies: phase 1 of the National Cooperative
      Inner-City Asthma Study (1992-1994) (cohort 1) and the Inner-City Asthma Study
      (1998-2001) (cohort 2). SETTING: Fifteen (8 for cohort 1 and 7 for cohort 2)
      major metropolitan inner-city areas in the United States. PARTICIPANTS: Inner
      city children aged 8 through 11 years with asthma. MAIN OUTCOME MEASURES:
      Proportion of children reclassified from less severe asthma categories based on
      symptom frequency into more severe categories because of lung function. RESULTS:
      Of children with symptoms of mild intermittent asthma, 22.8% in cohort 1 and
      27.7% in cohort 2 would be reclassified as having either moderate or severe
      persistent asthma. Of children with symptoms of mild persistent asthma, 31.2% in
      cohort 1 and 33.3% in cohort 2 would be similarly reclassified. CONCLUSIONS: In 2
      different studies of inner-city children with asthma, approximately one third of
      the participants were reclassified into higher National Asthma Education and
      Prevention Program asthma severity categories when pulmonary function was
      considered in addition to symptom frequency. This may have direct implications
      for the undertreatment of asthma.

PMID- 16894087
TI  - Laboratory testing for drug abuse.

PMID- 16894088
TI  - Neonatal adverse reactions after in utero exposure to selective serotonin
      reuptake inhibitors: still controversial.

PMID- 16894089
TI  - Limitations of study on alcohol advertising effects on youth drinking.

PMID- 16894090
TI  - Challenges to study on alcohol advertising effects on youth drinking.

PMID- 16894091
TI  - Patient page. Risk of fetal death and malformation related to seizure
      medications.

PMID- 16894093
TI  - The eyes as a window into disease prevention.

PMID- 16894094
TI  - How skeptical should we be about industry-sponsored studies?

PMID- 16894095
TI  - Communicating with the "locked-in" patient: because you can do it, should you?

PMID- 16894096
TI  - Immune reconstitution inflammatory syndrome in the CNS of HIV-infected patients.
AB  - OBJECTIVE: To describe challenges in diagnosis and management of patients with
      clinical syndromes of immune reconstitution inflammatory syndrome (IRIS)
      involving the CNS. METHODS: The authors describe three patients with clinically
      distinct neurologic manifestations of IRIS with HIV infection who presented as
      diagnostic and therapeutic challenges. RESULTS: One patient with cryptococcal
      meningitis developed acute cerebellitis with mass effect and brainstem
      compression. Corticosteroid therapy was associated with complete resolution of
      the cerebellar lesion but the patient developed VZV encephalitis. Another patient
      with progressive multifocal leukoencephalopathy developed subacute progression of
      focal neurologic deficits associated with contrast enhancing lesions on brain
      MRI. This patient had spontaneous resolution of the lesion but was left with
      residual deficits. One patient developed a progressive dementing syndrome and
      deterioration over several months resulting in coma during combination
      antiretroviral therapy. A brain biopsy in this latter patient showed massive
      infiltration of T lymphocytes predominantly of the CD8 subtype. This patient had
      a significant improvement with corticosteroids and change in antiretroviral
      regimen although she was left with residual cognitive impairment. CONCLUSIONS:
      Immune reconstitution inflammatory syndrome should be suspected in patients who
      show clinical or radiologic deterioration following initiation of antiretroviral
      therapy accompanied with improvement in CD4 cell count and viral load. Some
      patients may respond to a brief course of treatment with corticosteroids.

PMID- 16894097
TI  - Periodic alternating nystagmus with circumscribed nodular lesion.

PMID- 16894098
TI  - Cognitive effects of lamotrigine compared with topiramate in patients with
      epilepsy.
AB  - OBJECTIVE: To compare the cognitive effects of lamotrigine vs topiramate as
      adjunctive therapy in adults with epilepsy. METHODS: A multicenter, double-blind,
      randomized, prospective study was conducted in adults with partial seizures.
      Lamotrigine or topiramate was introduced as an adjunctive therapy to
      carbamazepine or phenytoin and titrated over 8 weeks to target doses. These drugs
      were maintained another 8 weeks (maintenance phase) without dosage changes. The
      primary endpoint was change from screening to the end of the maintenance phase in
      a combined analysis of standardized measures of cognition (Controlled Oral Word
      Association Task [COWA]; Stroop Color-Word Interference; Digit Cancellation;
      Lafayette Grooved Pegboard, dominant hand; Rey Auditory Verbal Learning Test,
      delayed recall; and Symbol-Digit Modalities test). RESULTS: For the primary
      endpoint, cognitive performance at the end of the maintenance phase was better
      with lamotrigine than with topiramate (415.3 vs 315.1; p < 0.001). On the
      individual cognitive tests, performance was better with lamotrigine than with
      topiramate in mean changes from screening on the COWA (p < 0.001), Stroop Color
      Word Interference (p = 0.038), and Symbol-Digit Modalities tests (p < 0.001). The
      treatment effect exceeded the minimum clinically important difference for the
      COWA and the Symbol-Digit Modalities test. Mean changes from screening in the
      Performance-On-Line test simulating driving skills reflected better performance
      with lamotrigine than with topiramate (p = 0.021). The median percentage change
      from baseline in seizure frequency was lower with lamotrigine than with
      topiramate during the escalation phase (-80% vs -100%; p = 0.028) but not during
      the maintenance phase (-75% vs -100%; p = 0.062). The frequencies of cognitive
      adverse events and of premature withdrawals related to cognitive decline were
      higher with topiramate than with lamotrigine (6% vs 0%; p = 0.013). CONCLUSION:
      Lamotrigine had significantly less impact than topiramate on measures of
      cognition when used as adjunctive therapy for partial seizures.

PMID- 16894100
TI  - Electroclinical features of absence seizures in childhood absence epilepsy.
AB  - OBJECTIVE: To accurately define the electroclinical features of absence seizures
      in children with newly diagnosed, untreated childhood absence epilepsy (CAE).
      METHODS: The authors searched an EEG database for absence seizures in normal
      children with new onset untreated absence epilepsy. Seventy consecutive children
      were classified into IGE syndromes. The clinical and EEG features of the seizures
      in the children with CAE were analyzed using video-EEG recordings. RESULTS: The
      authors analyzed 339 absence seizures in 47 children with CAE. The average
      seizure duration was 9.4 seconds and clinical features consisted of arrest of
      activity, loss of awareness, staring, and 3-Hz eyelid movements, but there was
      individual variation. Ictal EEG predominantly showed regular 3-Hz generalized
      spike and wave (GSW) with one or two spikes per wave; however, disorganization of
      discharges was common and three or more spikes per wave occurred rarely.
      Postictal slowing was frequent. Interictal abnormalities included fragments of
      GSW, posterior bilateral delta activity, and focal discharges. Although all 47
      children met the current criteria for CAE, only 5 fulfilled the recently proposed
      criteria for CAE. CONCLUSION: The heterogeneous nature of each clinical and EEG
      feature of untreated absence seizures is of critical importance when determining
      criteria for childhood absence epilepsy.

PMID- 16894099
TI  - In utero antiepileptic drug exposure: fetal death and malformations.
AB  - BACKGROUND: Pregnancy outcomes following in utero exposure to antiepileptic drugs
      (AEDs) are uncertain, limiting an evidenced-based approach. OBJECTIVE: To
      determine if fetal outcomes vary as a function of different in utero AED
      exposures. METHODS: This ongoing prospective observational study across 25
      epilepsy centers in the USA and UK enrolled pregnant women with epilepsy from
      October 1999 to February 2004 to determine if differential long-term cognitive
      and behavioral neurodevelopmental effects exist across the four most commonly
      used AEDs. This initial report focuses on the incidence of serious adverse
      outcomes including major congenital malformations (which could be attributable to
      AEDs) or fetal death. A total of 333 mother/child pairs were analyzed for
      monotherapy exposures: carbamazepine (n = 110), lamotrigine (n = 98), phenytoin
      (n = 56), and valproate (n = 69). RESULTS: Response frequencies of pregnancies
      resulting in serious adverse outcomes for each AED were as follows: carbamazepine
      8.2%, lamotrigine 1.0%, phenytoin 10.7%, and valproate 20.3%. Distribution of
      serious adverse outcomes differed significantly across AEDs and was not explained
      by factors other than in utero AED exposure. Valproate exhibited a dose-dependent
      effect. CONCLUSIONS: More adverse outcomes were observed in pregnancies with in
      utero valproate exposure vs the other antiepileptic drugs (AEDs). These results
      combined with several recent studies provide strong evidence that valproate poses
      the highest risk to the fetus. For women who fail other AEDs and require
      valproate, the dose should be limited if possible.

PMID- 16894101
TI  - Bilateral transverse sinus stenosis predicts IIH without papilledema in patients
      with migraine.
AB  - BACKGROUND: The headache profile of patients with idiopathic intracranial
      hypertension without papilledema (IIHWOP) may be indistinguishable from that of
      migraine. Bilateral transverse sinus stenosis (BTSS) has been found in the
      majority of patients with IIHWOP. The frequency of BTSS associated with IIHWOP in
      patients with migraine is unknown. OBJECTIVE: To detect the frequency of BTSS in
      adult patients with migraine and to investigate whether the presence of BTSS
      identifies patients with IIHWOP. METHODS: In a prospective study from December
      2000 to November 2005, 724 consecutive patients with recurrent headaches who
      fulfilled International Headache Society diagnostic criteria for migraine
      underwent cerebral MR venography (MRV). A portion of these patients underwent a
      lumbar puncture (LP) to measure CSF pressure. MRV and LP were also performed in
      70 age-matched control subjects. RESULTS: Six hundred seventy-five of the 724
      patients with migraines had normal MRV. Seventy of these 675 patients underwent
      LP, and all of them had normal CSF pressure. Forty-nine (6.7%) of the 724
      patients with migraine had BTSS. Twenty-eight of these 49 patients with BTSS
      underwent LP, and 19 (67.8%) had IIHWOP. The headache profiles of patients with
      BTSS and IIHWOP did not differ from those of patients with normal MRVs and CSF
      pressures within normal limits. CSF pressure was normal in both patients and
      controls with normal MRV. CONCLUSIONS: Of patients with migraine, 6.7% had
      bilateral transverse sinus stenosis; 67.8% of these patients had idiopathic
      intracranial hypertension without papilledema (IIHWOP). These results suggest
      that patients with migraine who present bilateral transverse sinus stenosis on
      cerebral MR venography should undergo lumbar puncture to exclude IIHWOP.

PMID- 16894102
TI  - Intracerebral hemorrhage in pregnancy: frequency, risk factors, and outcome.
AB  - OBJECTIVE: To describe the frequency, risk factors, and outcome of intracerebral
      hemorrhage (ICH) in pregnancy and the postpartum period using a large database of
      US inpatient hospitalizations. METHODS: The authors obtained data from an
      administrative dataset, the Nationwide Inpatient Sample, which includes
      approximately 20% of all discharges from non-Federal hospitals, for the years
      1993 through 2002. Women aged 15 to 44 years with a diagnosis of ICH were
      selected from the database for analysis, and within this group patients coded as
      pregnant or postpartum were identified. Using US Census data, estimates were made
      of the rates of ICH in pregnant/postpartum and non-pregnant women. Rates of
      various comorbidities in patients with pregnancy-related ICH were compared to the
      rates found in the general population of delivering patients using multivariate
      logistic regression to identify independent risk factors for pregnancy-related
      ICH. RESULTS: The authors identified 423 patients with pregnancy-related ICH,
      which corresponded to 6.1 pregnancy-related ICH per 100,000 deliveries and 7.1
      pregnancy-related ICH per 100,000 at-risk person-years (compared to 5.0 per
      100,000 person-years for non-pregnant women in the age range considered). The
      increased risk of ICH associated with pregnancy was largely attributable to ICH
      occurring in the postpartum period. The in-hospital mortality rate for pregnancy
      related ICH was 20.3%. ICH accounted for 7.1% of all pregnancy-related mortality
      recorded in this database. Significant independent risk factors for pregnancy
      related ICH included advanced maternal age (OR 2.11, 95% CI 1.69 to 2.64),
      African American race (OR 1.83, 95% CI 1.39 to 2.41), preexisting hypertension
      (OR 2.61, 95% CI 1.34 to 5.07), gestational hypertension (OR 2.41, 95% CI 1.62 to
      3.59), preeclampsia/eclampsia (OR 10.39, 95% CI 8.32 to 12.98), preexisting
      hypertension with superimposed preeclampsia/eclampsia (OR 9.23, 95% CI 5.26 to
      16.19), coagulopathy (OR 20.66, 95% CI 13.67 to 31.23), and tobacco abuse (OR
      1.95, 95% CI 1.11 to 3.42). CONCLUSION: Intracerebral hemorrhage (ICH) accounts
      for a substantial portion of pregnancy-related mortality. The risk of ICH
      associated with pregnancy is greatest in the postpartum period. Advanced maternal
      age, African American race, hypertensive diseases, coagulopathy, and tobacco
      abuse were all independent risk factors for pregnancy-related ICH.

PMID- 16894103
TI  - The Spastic Paraplegia Rating Scale (SPRS): a reliable and valid measure of
      disease severity.
AB  - OBJECTIVE: To develop and evaluate a clinical Spastic Paraplegia Rating Scale
      (SPRS) to measure disease severity and progression. METHODS: A 13-item scale was
      designed to rate functional impairment occurring in pure forms of spastic
      paraplegia (SP). Additional symptoms constituting a complicated form of SP are
      recorded in an inventory. Two independent patient cohorts were evaluated in a two
      step validation procedure. RESULTS: Application of SPRS requires less than 15
      minutes and does not require any special equipment, so it is suitable for an
      outpatient setting. Interrater agreement of SPRS was high (intraclass correlation
      coefficient = 0.99). Reliability was further supported by high internal
      consistency (Cronbach alpha = 0.91). SPRS values were almost normally distributed
      without apparent floor or ceiling effect. Construct validity was shown by high
      correlation of SPRS to Barthel Index and the International Cooperative Ataxia
      Rating Scale (convergent validity) and low correlation to Mini-Mental Status
      Examination (discriminant validity). CONCLUSION: The Spastic Paraplegia Rating
      Scale is a reliable and valid measure of disease severity.

PMID- 16894104
TI  - Education and the cognitive decline associated with MRI-defined brain infarct.
AB  - OBJECTIVE: To assess whether educational attainment, a correlate of cognitive
      reserve, predicts the amount of cognitive decline associated with a new brain
      infarct. METHODS: The Cardiovascular Health Study is a population-based,
      longitudinal study of people aged 65 years and older. Cognitive function was
      measured annually using the Modified Mini-Mental State Examination (3MS) and the
      Digit-Symbol Substitution Test (DSST). The authors tested whether education level
      modified 1) the cross-sectional association between cognitive performance and MRI
      defined infarct and 2) the change in cognitive function associated with an
      incident infarct at a follow-up MRI. RESULTS: In cross-sectional analysis (n =
      3,660), MRI-defined infarct was associated with a greater impact on 3MS
      performance in the lowest education quartile when compared with others (p for
      heterogeneity = 0.012). Among those with a follow-up MRI who had no infarct on
      initial MRI (n = 1,433), education level was not associated with the incidence,
      size, or location of new brain infarct. However, a new MRI-defined infarct
      predicted substantially greater decline in 3MS scores in the lowest education
      group compared with the others (6.3, 95% CI 4.4- to 8.2-point decline vs 1.7, 95%
      CI 0.7- to 2.7-point decline; p for heterogeneity < 0.001). Higher education was
      not associated with smaller declines in DSST performance in the setting of MRI
      defined infarct. CONCLUSIONS: Education seems to modify an individual's decline
      on a test of general cognitive function when there is incident brain infarct.
      These findings are consistent with the hypothesis that cognitive reserve
      influences the impact of vascular injury in the brain.

PMID- 16894105
TI  - Mild cognitive impairment: risk of Alzheimer disease and rate of cognitive
      decline.
AB  - OBJECTIVE: To examine the extent to which persons with mild cognitive impairment
      (MCI) have an increased risk of Alzheimer disease (AD) and a more rapid rate of
      decline in cognitive function compared to similar persons without cognitive
      impairment. METHOD: Participants were 786 community-based persons (221 with MCI
      and 565 without cognitive impairment) from the Rush Memory and Aging Project, an
      ongoing longitudinal clinical-pathologic study of common chronic conditions of
      old age. All participants underwent detailed annual clinical and
      neuropsychological evaluations. The authors examined the risk of incident AD and
      rate of change in global cognitive function among persons with MCI and those
      without cognitive impairment; all statistical models controlled for age, sex, and
      education. RESULTS: Over an average of 2.5 years of follow-up, 57 persons with
      MCI (25.8%) developed AD, a rate 6.7 times higher than those without cognitive
      impairment. In addition, persons with MCI declined considerably more rapidly each
      year on a measure of global cognitive function than those without cognitive
      impairment. CONCLUSIONS: Mild cognitive impairment is associated with a greatly
      increased risk of incident Alzheimer disease and a more rapid rate of decline in
      cognitive function.

PMID- 16894106
TI  - [11C]PIB in a nondemented population: potential antecedent marker of Alzheimer
      disease.
AB  - BACKGROUND: Beta-amyloid (Abeta) plaques are the hallmark of Alzheimer disease
      (AD). A PET imaging tracer that binds to Abeta plaques in vivo, N-methyl-[(11)C]2
      (4'-methylaminophenyl)-6-hydroxybenzothiazole (or [(11)C]PIB for "Pittsburgh
      Compound-B"), has significantly higher binding in subjects diagnosed with
      dementia of the Alzheimer type (DAT) compared to nondemented controls. The
      authors used this imaging technique to investigate whether abnormal binding
      occurs in clinically normal individuals, prior to the development of cognitive
      changes. METHODS: Forty-one nondemented subjects (age range 20 to 86 years) and
      10 patients with DAT (age range 66 to 86 years) underwent [(11)C]PIB PET
      scanning. Regions of interest were drawn on the MRI over the cerebellar,
      prefrontal, lateral temporal, occipital, gyrus rectus, precuneus, and striatal
      cortex. Binding potential values (BPs), proportional to the density of [(11)C]PIB
      Abeta binding sites, were calculated using the Logan graphical analysis and the
      cerebellar cortex for a reference tissue. RESULTS: Patients with DAT had elevated
      BP values vs nondemented subjects (p < 0.0001). Four of the 41 nondemented
      subjects had elevated cortical BP values and their BP values as a group were not
      significantly different from the DAT subjects' BP values. Two of these four
      nondemented subjects had [(11)C]PIB uptake, both visually and quantitatively,
      that was indistinguishable from the DAT subjects. CONCLUSIONS: Elevated
      [(11)C]PIB binding in nondemented subjects suggests that [(11)C]PIB amyloid
      imaging may be sensitive for detection of a preclinical Alzheimer disease state.
      Longitudinal studies will be required to determine the association of elevated
      [(11)C]PIB binding and risk of developing dementia of the Alzheimer type.

PMID- 16894107
TI  - The contribution of voxel-based morphometry in staging patients with mild
      cognitive impairment.
AB  - OBJECTIVE: To assess whether different patterns of regional gray matter loss in
      patients with mild cognitive impairment (MCI) are associated with different risks
      of conversion to Alzheimer disease (AD), using MRI and voxel-based morphometry
      (VBM). METHODS: The authors recruited 22 patients with MCI, 22 patients with
      probable AD, and 20 healthy subjects (HS). T1 volumes from each subject were
      postprocessed according to an optimized VBM protocol. All patients were
      clinically followed up (mean [SD] time = 28.7 [5.7] months), and patients with
      MCI were reclassified into two groups (converters and nonconverters to AD).
      RESULTS: When comparing patients with AD to HS, widespread areas of reduced gray
      matter density were found predominantly in temporal, frontal, and parietal lobes
      and in the insula. Comparing MCI converters and nonconverters with HS, the
      converters showed more widespread areas of reduced gray matter density than
      nonconverters, with a pattern of abnormalities similar to that seen in patients
      with AD. Conversely, when comparing the same groups with patients with AD, MCI
      nonconverters showed a pattern of gray matter density similar to that of HS.
      Areas of decreased gray matter density were also found in MCI converters compared
      with nonconverters. CONCLUSIONS: Different patterns of gray matter density
      distribution in patients with mild cognitive impairment may be associated to
      different rates of conversion to Alzheimer disease.

PMID- 16894108
TI  - Restriction in complex activities of daily living in MCI: impact on outcome.
AB  - OBJECTIVE: To describe the restriction in instrumental activities of daily living
      (IADL) in mild cognitive impairment (MCI) and to assess the impact of IADL
      restriction on the progression to dementia and on MCI reversibility. METHODS: The
      study sample included 1,517 participants of the PAQUID cohort, visited at 8- and
      10-year follow-ups. Subjects classified as having MCI had no dementia but a
      cognitive deficit according to five neuropsychological tests. Four IADL
      (telephone, transports, medication, finances) were assessed and considered
      restricted if at least two of them were not performed at the highest level of
      performance. Cross-sectional and longitudinal analyses were conducted. RESULTS: A
      total of 285 subjects were classified as having MCI at baseline, and 15.2%
      developed dementia within 2 years. MCI subjects were more frequently IADL
      restricted (34.3%) than controls (5.4%) but less than those with dementia
      (91.1%). The IADL-restricted MCI subjects were more likely to develop dementia
      over 2 years (30.7%) than the nonrestricted ones (7.8%). In multivariate
      analyses, the odds ratio for dementia was 7.4 (CI: 3.3 to 16.5) in the IADL
      restricted MCI and 2.8 (CI: 1.3 to 6.0) in the non-IADL-restricted MCI compared
      with the non-IADL-restricted controls. IADL restriction also lowered the chance
      of reversibility to normal, observed in 10.7% of the restricted MCI and 34.7% of
      the nonrestricted MCI. CONCLUSIONS: Inclusion of instrumental activities of daily
      living restriction in the criteria of mild cognitive impairment improves the
      prediction of dementia and the stability of this status over time. Conversely,
      its exclusion results in inappropriate selection of subjects with a low
      probability of short-term progression to dementia.

PMID- 16894109
TI  - Longitudinal course and neuropathologic outcomes in original vs revised MCI and
      in pre-MCI.
AB  - OBJECTIVES: To compare the natural history of individuals classified with mild
      cognitive impairment (MCI) in accordance with original criteria to the natural
      history of individuals classified with revised MCI criteria. METHODS: The authors
      compared the rates of progression in 32 individuals with amnestic MCI and in 90
      people with MCI according to revised criteria that allow nonamnestic deficits
      with progression in 276 individuals who were too minimally impaired (pre-MCI) to
      meet either MCI criteria. All individuals in this study were determined
      clinically to be very mildly cognitively impaired with a Clinical Dementia Rating
      (CDR) of 0.5. RESULTS: Rates of progression for the two MCI groups were similar
      with a decline of almost 0.50 SD per year on a psychometric composite. Decline
      was less (0.23 SD) in the pre-MCI group. Median survival time to CDR 1 (mild
      dementia) was comparable for the original (95% CI: 3.79 to 4.07 years) and
      revised (95% CI: 3.29 to 5.40) criteria MCI groups but approximately twice as
      long in the pre-MCI group (95% CI: 6.72 to 8.93). All cases from the amnestic MCI
      criteria group with neuropathologic diagnoses met criteria for Alzheimer disease
      as did more than 90% in the other two groups. CONCLUSIONS: Mild cognitive
      impairment as originally and currently defined is usually early stage Alzheimer
      disease, which can begin with a cognitive deficit other than memory. It is
      possible to identify Alzheimer disease at an even earlier stage than mild
      cognitive impairment by focusing on intraindividual change rather than comparison
      with group norms.

PMID- 16894110
TI  - CSF analysis differentiates multiple-system atrophy from idiopathic late-onset
      cerebellar ataxia.
AB  - BACKGROUND: Differentiating idiopathic late-onset cerebellar ataxia (ILOCA) from
      ataxia due to the cerebellar subtype of multiple-system atrophy (MSA-C) can be
      difficult in the early stages of the disease METHODS: The authors analyzed the
      levels of various CSF biomarkers in 27 patients with MSA-C and 18 patients with
      ILOCA and obtained cut-off points for each potential biomarker to differentiate
      MSA-C from ILOCA. RESULTS: Increased levels of neurofilament light chain (NFL)
      and neurofilament heavy chain (NFHp35) and decreased levels of the
      neurotransmitter metabolites homovanillic acid (HVA), 5-hydroxyindoleaceticacid
      (5-HIAA), and 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) were observed in MSA
      C compared with ILOCA patients. Receiver operating characteristic analysis showed
      high sensitivity and specificity levels for NFL, NFHp35, and MHPG analysis. At a
      cut-off of 24.4 ng/L for the NFL analysis, a sensitivity of 79% and a specificity
      of 94% were obtained for differentiating MSA-C from ILOCA. At a cut-off point for
      NFHp35 of 129.5 ng/L, sensitivity was 87% and specificity 83%. Analysis of MHPG
      levels (cut-off 42.5 nM) resulted in a sensitivity of 86% with a specificity of
      75%. A multivariate logistic regression model selected NFL, MHPG, and tau as
      independent predictive biomarkers that separated the MSA-C and ILOCA groups.
      CONCLUSIONS: Increased levels of neurofilament light chain and tau and decreased
      levels of 3-methoxy-4-hydroxyphenylethyleneglycol were associated with high
      accuracy levels in differentiating the cerebellar subtype of multiple-system
      atrophy from idiopathic late-onset cerebellar ataxia (LOCA). CSF analysis may
      thus serve as a useful tool in early diagnostic differentiation of LOCA.

PMID- 16894112
TI  - Painful hand and moving finger treated by wearing a glove.
AB  - The authors report a patient with unilateral painful hand and moving finger in
      whom tactile stimulation interrupted both the movement and the pain. This effect
      suggests a gating mechanism at a segmental level. The difference between afferent
      and efferent pathway levels and the delay of several months between trauma and
      occurrence of symptoms support a central mechanism, most probably involving
      sensorimotor reorganization at a segmental level.

PMID- 16894111
TI  - When do patients with Parkinson disease disclose their diagnosis?
AB  - The authors surveyed 101 patients with Parkinson disease (PD) about their
      experiences disclosing the diagnosis. Ninety percent disclosed early to family;
      more than 25% waited at least 1 year to disclose at work. The main concerns about
      disclosure were fear of reflecting negatively on themselves and fear of upsetting
      others. Patients who delayed disclosure were more likely male, younger, and
      employed. There is considerable variability among patients with PD in the time to
      disclose their diagnosis.

PMID- 16894113
TI  - Transcranial cerebral herniation after chronic subdural hematoma treatment with
      no dura closure.

PMID- 16894114
TI  - Immunologic diseases, anti-inflammatory drugs, and Parkinson disease: a case
      control study.
AB  - The authors studied the association of markers of inflammation with the later
      development of Parkinson disease (PD) using a case-control design (196 cases and
      196 matched controls). The frequency of diseases of immediate-type
      hypersensitivity was significantly higher in cases than controls. In addition,
      cases used anti-inflammatory agents less frequently than controls (nonsignificant
      trend). The results may support the hypothesis that there is an inflammatory
      component in the pathogenesis of PD.

PMID- 16894115
TI  - Progressive depletion of mtDNA in mitochondrial myopathy.
AB  - The authors studied seven patients with mitochondrial DNA (mtDNA) myopathy. Over
      time, there was a progressive depletion of mtDNA, which preferentially affected
      wild-type mitochondrial genomes. This suggests that loss of wild-type mtDNA is a
      major feature of mtDNA myopathy, and preventing wild-type mtDNA depletion has
      treatment implications.

PMID- 16894116
TI  - MRI features of spongiform leukoencephalopathy following heroin inhalation.

PMID- 16894117
TI  - Anti-MuSK antibodies: correlation with myasthenia gravis severity.
AB  - The authors measured anti-muscle-specific tyrosine kinase (anti-MuSK) antibodies
      (Abs) in 83 serum samples from 40 patients and evaluated their correlation with
      myasthenia gravis severity and treatment response. Ab concentrations were often
      reduced by immunosuppression but not after thymectomy. Both in individual cases
      and in the whole population, a correlation between Ab levels and disease severity
      was found.

PMID- 16894118
TI  - Lack of association of VEGF promoter polymorphisms with sporadic ALS.
AB  - The authors tested the association of three vascular endothelial growth factor
      (VEGF) promoter polymorphisms with sporadic ALS (SALS) to verify the results of a
      previous study and to investigate their modifier effects on the subphenotypes of
      SALS in a large family-based and case-control cohort of North American white
      subjects (N = 1,603). They did not find any association of the VEGF promoter
      polymorphisms with SALS or its subphenotypes, suggesting that they do not have a
      direct causal role in ALS.

PMID- 16894119
TI  - Parity and risk of death from subarachnoid hemorrhage in women: evidence from a
      cohort in Taiwan.
AB  - The authors examined the relationship in women between age at first birth,
      parity, and subarachnoid hemorrhage mortality. They followed each woman from the
      time of her first birth and linked vital status with a mortality database. The
      risk was increased by 8% for each additional year of mother's age at first birth.
      The relative risk was 0.63 for women who had borne two children and 0.62 for
      women with three or more births.

PMID- 16894120
TI  - How well does ASPECTS predict the outcome of acute stroke treated with IV tPA?
AB  - The authors measured the association of early ischemic change on CT scan,
      measured using the Alberta Stroke Programme Early CT score (ASPECTS), and
      functional outcome in 825 patients with anterior circulation stroke treated with
      IV thrombolysis within 3 hours of onset. ASPECTS predicted outcome in a graded
      fashion (linearly for ASPECTS 6 through 10; pattern ill-defined for ASPECTS 0
      through 5) but discriminated individual outcomes weakly. Except perhaps when
      early ischemic change is extensive, clinicians should not estimate prognosis
      using ASPECTS alone.

PMID- 16894121
TI  - Diffusion tensor MRI shows abnormal brainstem crossing fibers associated with
      ROBO3 mutations.
AB  - Horizontal gaze palsy with progressive scoliosis (HGPPS) is caused by mutations
      in the ROBO3 gene, critical for the crossing of long ascending medial lemniscal
      and descending corticospinal tracts in the medulla. Diffusion tensor imaging in a
      patient with HGGPS revealed the absence of major pontine crossing fiber tracts
      and no decussation of the superior cerebellar peduncles. Mutations in the ROBO3
      gene lead to a widespread lack of crossing fibers throughout the brainstem.

PMID- 16894122
TI  - Developing somatosensory projections bypass periventricular brain lesions.
AB  - The authors studied four hemiparetic patients with large unilateral
      periventricular brain lesions acquired during the early third trimester of
      pregnancy. fMRI and magnetoencephalography demonstrated that the primary
      somatosensory representation of their paretic hands was nevertheless located in
      the contralateral rolandic cortex. Thus, outgrowing thalamocortical somatosensory
      projections had apparently bypassed the lesion to reach their original cortical
      destination. Such somatosensory projections curving around the lesion were
      effectively visualized by magnetic resonance diffusion tractography.

PMID- 16894123
TI  - The effect of APOE genotype on clinical phenotype in Alzheimer disease.
AB  - The authors classified 100 patients with Alzheimer disease (AD) as presenting
      with a memory or nonmemory phenotype. APOE genotype was determined. There was an
      association between APOE-epsilon4 and clinical phenotype (odds ratio = 3.0; 95%
      CI: 1.2 to 7.8), suggesting that two subtypes of AD can be identified. The
      typical amnestic phenotype seems to be promoted by the APOE-epsilon4 allele,
      whereas the atypical nonmemory phenotype occurs in the absence of the APOE
      epsilon4 allele.

PMID- 16894124
TI  - Treatment monitoring and response prediction with proton MR spectroscopy in AD.
AB  - In this proton magnetic resonance spectroscopy ((1)H-MRS) study, the authors
      correlated cognitive improvement after 3 months of treatment with donepezil with
      changes of N-acetylaspartate (NAA) level and NAA/Creatine (Cr) ratio in the
      medial temporal and parietal lobe of 17 patients with Alzheimer disease.
      Treatment response was associated with an increase of NAA and NAA/Cr in the
      parietal lobe. Low baseline NAA/Cr in the parietal lobe predicted positive
      treatment outcome.

PMID- 16894125
TI  - The MM2-cortical form of sporadic Creutzfeldt-Jakob disease presenting with
      visual disturbance.
AB  - A subclass of sporadic Creutzfeldt-Jakob disease (sCJD) characterized by onset
      with visual symptoms (Heidenhain variant) has been reported to belong to the MM1
      or MV1 type according to Parchi's classification. The authors report a 65-year
      old woman with MM2-cortical sCJD with slowly progressive visual disturbance as
      the initial symptom. Diffusion-weighted MRIs revealed hyperintensity in both
      occipital cortices at an early stage.

PMID- 16894126
TI  - Communication in locked-in syndrome: effects of imagery on salivary pH.

PMID- 16894127
TI  - Two first-degree relatives with perimesencephalic nonaneurysmal hemorrhage.

PMID- 16894129
TI  - Early MR imaging and spectroscopy appearance of eIF2B-related
      leukoencephalopathy.

PMID- 16894128
TI  - Extracranial internal carotid artery dissection with unusual gadolinium
      enhancement.

PMID- 16894130
TI  - Onset of Creutzfeldt-Jakob disease mimicking an acute cerebrovascular event.

PMID- 16894131
TI  - Recurrent ibuprofen-induced aseptic meningitis: evidence against an antigen
      specific immune response.

PMID- 16894132
TI  - On call...

PMID- 16894133
TI  - Is protracted low-dose temozolomide feasible in glioma patients?

PMID- 16894134
TI  - Acute motor conduction block neuropathy followed by axonal degeneration and poor
      recovery.

PMID- 16894135
TI  - Use of serum prolactin in diagnosing epileptic seizures: report of the
      Therapeutics and Technology Assessment Subcommittee of the American Academy of
      Neurology.

PMID- 16894140
TI  - Stable neuron numbers from cradle to grave.

PMID- 16894142
TI  - Poxy models and rash decisions.

PMID- 16894141
TI  - Transforming properties of YAP, a candidate oncogene on the chromosome 11q22
      amplicon.
AB  - In a screen for gene copy-number changes in mouse mammary tumors, we identified a
      tumor with a small 350-kb amplicon from a region that is syntenic to a much
      larger locus amplified in human cancers at chromosome 11q22. The mouse amplicon
      contains only one known gene, Yap, encoding the mammalian ortholog of Drosophila
      Yorkie (Yki), a downstream effector of the Hippo(Hpo)-Salvador(Sav)-Warts(Wts)
      signaling cascade, recently identified in flies as a critical regulator of
      cellular proliferation and apoptosis. In nontransformed mammary epithelial cells,
      overexpression of human YAP induces epithelial-to-mesenchymal transition,
      suppression of apoptosis, growth factor-independent proliferation, and anchorage
      independent growth in soft agar. Together, these observations point to a
      potential oncogenic role for YAP in 11q22-amplified human cancers, and they
      suggest that this highly conserved signaling pathway identified in Drosophila
      regulates both cellular proliferation and apoptosis in mammalian epithelial
      cells.

PMID- 16894143
TI  - Type 1, type 1.5, and type 2 diabetes: NOD the diabetes we thought it was.

PMID- 16894144
TI  - A redox-active FKBP-type immunophilin functions in accumulation of the
      photosystem II supercomplex in Arabidopsis thaliana.
AB  - Photosystem II (PSII) catalyzes the first of two photosynthetic reactions that
      convert sunlight into chemical energy. Native PSII is a supercomplex consisting
      of core and light-harvesting chlorophyll proteins. Although the structure of PSII
      has been resolved by x-ray crystallography, the mechanism underlying its assembly
      is poorly understood. Here, we report that an immunophilin of the chloroplast
      thylakoid lumen is required for accumulation of the PSII supercomplex in
      Arabidopsis thaliana. The immunophilin, FKBP20-2, belongs to the FK-506 binding
      protein (FKBP) subfamily that functions as peptidyl-prolyl isomerases (PPIases)
      in protein folding. FKBP20-2 has a unique pair of cysteines at the C terminus and
      was found to be reduced by thioredoxin (Trx) (itself reduced by NADPH by means of
      NADP-Trx reductase). The FKBP20-2 protein, which contains only two of the five
      amino acids required for catalysis, showed a low level of PPIase activity that
      was unaffected on reduction by Trx. Genetic disruption of the FKBP20-2 gene
      resulted in reduced plant growth, consistent with the observed lower rate of PSII
      activity determined by fluorescence (using leaves) and oxygen evolution (using
      isolated chloroplasts). Analysis of isolated thylakoid membranes with blue native
      gels and immunoblots showed that accumulation of the PSII supercomplex was
      compromised in mutant plants, whereas the levels of monomer and dimer building
      blocks were elevated compared with WT. The results provide evidence that FKBP20-2
      participates specifically in the accumulation of the PSII supercomplex in the
      chloroplast thylakoid lumen by means of a mechanism that has yet to be
      determined.

PMID- 16894145
TI  - Severe acute respiratory syndrome-associated coronavirus 3a protein forms an ion
      channel and modulates virus release.
AB  - Fourteen ORFs have been identified in the severe acute respiratory syndrome
      associated coronavirus (SARS-CoV) genome. ORF 3a of SARS-CoV codes for a recently
      identified transmembrane protein, but its function remains unknown. In this study
      we confirmed the 3a protein expression and investigated its localization at the
      surface of SARS-CoV-infected or 3a-cDNA-transfected cells. Our experiments showed
      that recombinant 3a protein can form a homotetramer complex through interprotein
      disulfide bridges in 3a-cDNA-transfected cells, providing a clue to ion channel
      function. The putative ion channel activity of this protein was assessed in 3a
      complement RNA-injected Xenopus oocytes by two-electrode voltage clamp. The
      results suggest that 3a protein forms a potassium sensitive channel, which can be
      efficiently inhibited by barium. After FRhK-4 cells were transfected with an
      siRNA, which is known to suppress 3a expression, followed by infection with SARS
      CoV, the released virus was significantly decreased, whereas the replication of
      the virus in the infected cells was not changed. Our observation suggests that
      SARS-CoV ORF 3a functions as an ion channel that may promote virus release. This
      finding will help to explain the highly pathogenic nature of SARS-CoV and to
      develop new strategies for treatment of SARS infection.

PMID- 16894146
TI  - Broad-spectrum biofilm inhibition by a secreted bacterial polysaccharide.
AB  - The development of surface-attached biofilm bacterial communities is considered
      an important source of nosocomial infections. Recently, bacterial interference
      via signaling molecules and surface active compounds was shown to antagonize
      biofilm formation, suggesting that nonantibiotic molecules produced during
      competitive interactions between bacteria could be used for biofilm reduction.
      Hence, a better understanding of commensal/pathogen interactions within bacterial
      community could lead to an improved control of exogenous pathogens. To reveal
      adhesion or growth-related bacterial interference, we investigated interactions
      between uropathogenic and commensal Escherichia coli in mixed in vitro biofilms.
      We demonstrate here that the uropathogenic strain CFT073 and all E. coli
      expressing group II capsules release into their environment a soluble
      polysaccharide that induces physicochemical surface alterations, which prevent
      biofilm formation by a wide range of Gram-positive and Gram-negative bacteria. We
      show that the treatment of abiotic surfaces with group II capsular
      polysaccharides drastically reduces both initial adhesion and biofilm development
      by important nosocomial pathogens. These findings identify capsular polymers as
      antiadhesion bacterial interference molecules, which may prove to be of
      significance in the design of new strategies to limit biofilm formation on
      medical in dwelling devices.

PMID- 16894148
TI  - Interstellar chemistry.
AB  - In the past half century, radioastronomy has changed our perception and
      understanding of the universe. In this issue of PNAS, the molecular chemistry
      directly observed within the galaxy is discussed. For the most part, the
      description of the molecular transformations requires specific kinetic schemes
      rather than chemical thermodynamics. Ionization of the very abundant molecular
      hydrogen and atomic helium followed by their secondary reactions is discussed.
      The rich variety of organic species observed is a challenge for complete
      understanding. The role and nature of reactions involving grain surfaces as well
      as new spectroscopic observations of interstellar and circumstellar regions are
      topics presented in this special feature.

PMID- 16894147
TI  - The first three domains of the insulin receptor differ structurally from the
      insulin-like growth factor 1 receptor in the regions governing ligand
      specificity.
AB  - The insulin receptor (IR) and the type-1 insulin-like growth factor receptor
      (IGF1R) are homologous multidomain proteins that bind insulin and IGF with
      differing specificity. Here we report the crystal structure of the first three
      domains (L1-CR-L2) of human IR at 2.3 A resolution and compare it with the
      previously determined structure of the corresponding fragment of IGF1R. The most
      important differences seen between the two receptors are in the two regions
      governing ligand specificity. The first is at the corner of the ligand-binding
      surface of the L1 domain, where the side chain of F39 in IR forms part of the
      ligand binding surface involving the second (central) beta-sheet. This is very
      different to the location of its counterpart in IGF1R, S35, which is not involved
      in ligand binding. The second major difference is in the sixth module of the CR
      domain, where IR contains a larger loop that protrudes further into the ligand
      binding pocket. This module, which governs IGF1-binding specificity, shows
      negligible sequence identity, significantly more alpha-helix, an additional
      disulfide bond, and opposite electrostatic potential compared to that of the
      IGF1R.

PMID- 16894150
TI  - Embryonic stem cells make human T cells.

PMID- 16894149
TI  - Infant brains detect arithmetic errors.
AB  - A current debate is whether increased looking time in infancy is related to
      violation of expectations. In this study, 6- to 9-month-old infants' brain
      activity was analyzed during presentation of correct and incorrect solutions to
      simple arithmetic equations [(e.g., presentation of 1 + 1; one doll on a TV
      monitor, with another doll added from behind a screen, followed by a solution of
      2 (correct) or 1 (incorrect)]. Infants looked longer at incorrect solutions than
      at correct ones. Event-related potentials, time-locked to the presentation of the
      solution, also differed between conditions, with greater negative activity for
      the incorrect solution condition. Spectral analysis showed a similar pattern to
      that of adults observing correct and incorrect arithmetical equations. These
      findings show (i) that the brain network involved in error detection can be
      identified in infancy and (ii) that this network can support an association
      between looking time and violation of expectations.

PMID- 16894151
TI  - Ice-age endurance: DNA evidence of a white spruce refugium in Alaska.
AB  - Paleorecords offer key information for evaluating model simulations of species
      migration in response to forecast climatic change. However, their utility can be
      greatly compromised by the existence of glacial refugia that are undetectable in
      fossil records (cryptic refugia). Despite several decades of investigation, it
      remains controversial whether Beringia, the largely unglaciated area extending
      from northeastern Siberia to the Yukon Territory, harbored small populations of
      certain boreal tree species during the last glaciation. Here, we present genetic
      evidence for the existence of a glacial refuge in Alaska that helps to resolve
      this long-standing controversy. We sequenced chloroplast DNA (cpDNA) of white
      spruce (Picea glauca), a dominant boreal tree species, in 24 forest stands across
      northwestern North America. The majority of cpDNA haplotypes are unique, and
      haplotype diversity is relatively high in Alaska, arguing against the possibility
      that this species migrated into the region from areas south of the Laurentide Ice
      Sheet after the end of the last glaciation. Thus, white spruce apparently
      survived long glacial episodes under climatic extremes in a heterogeneous
      landscape matrix. These results suggest that estimated rates of tree migration
      from fossil records may be too high and that the ability of trees to track
      anthropogenic warming may be more limited than previously thought.

PMID- 16894152
TI  - Analysis of Aurignacian interstratification at the Chatelperronian-type site and
      implications for the behavioral modernity of Neandertals.
AB  - The Chatelperronian is a Neandertal-associated archeological culture featuring
      ornaments and decorated bone tools. It is often suggested that such symbolic
      items do not imply that Neandertals had modern cognition and stand instead for
      influences received from coeval, nearby early modern humans represented by the
      Aurignacian culture, whose precocity would be proven by stratigraphy and
      radiocarbon dates. The Grotte des Fees at Chatelperron (France) is the remaining
      case of such a potential Chatelperronian-Aurignacian contemporaneity, but
      reanalysis shows that its stratification is poor and unclear, the bone assemblage
      is carnivore-accumulated, the putative interstratified Aurignacian lens in level
      B4 is made up for the most part of Chatelperronian material, the upper part of
      the sequence is entirely disturbed, and the few Aurignacian items in levels B4-5
      represent isolated intrusions into otherwise in situ Chatelperronian deposits. As
      elsewhere in southwestern Europe, this evidence confirms that the Aurignacian
      postdates the Chatelperronian and that the latter's cultural innovations are
      better explained as the Neandertals' independent development of behavioral
      modernity.

PMID- 16894153
TI  - Osteogenic differentiation of mouse adipose-derived adult stromal cells requires
      retinoic acid and bone morphogenetic protein receptor type IB signaling.
AB  - Although the multilineage potential of human adipose-derived adult stromal cells
      (ADAS) has been well described, few published studies have investigated the
      biological and molecular mechanisms underlying osteogenic differentiation of
      mouse ADAS. We report here that significant osteogenesis, as determined by gene
      expression and histological analysis, is induced only when mouse ADAS are
      cultured in the presence of retinoic acid with or without recombinant human bone
      morphogenetic protein (BMP)-2 supplementation. Furthermore, a dynamic expression
      profile for the BMP receptor (BMPR) isoform IB was observed, with dramatic up
      regulation during osteogenesis. Western blot analysis revealed that retinoic acid
      enhanced levels of BMPR-IB protein during the first 7 days of osteogenic
      differentiation and that RNAi-mediated suppression of BMPR-IB dramatically
      impaired the ability of ADAS to form bone in vitro. In contrast, absence of BMPR
      IA did not significantly diminish ADAS osteogenesis. Our data therefore
      demonstrate that the osteogenic commitment of multipotent mouse ADAS requires
      retinoic acid, which enhances expression of the critical BMPR-IB isoform.

PMID- 16894154
TI  - Resorcinarenes are hexameric capsules in solution.
AB  - The host-guest complexes of resorcin[4]arenes with small molecules in organic
      solutions are examined using modern NMR spectroscopic methods. The complexation
      of glutaric acid and beta-methyl d-glucopyranoside in chloroform were
      investigated through 2D COSY, 2D NOESY, 1D NOE, and diffusion-ordered NMR
      spectroscopy (DOSY) techniques. These methods indicate that the complex is a self
      assembled capsule composed of six resorcinarenes that surround six guest
      molecules of glutaric acid or three molecules of beta-methyl d-glucopyranoside
      inside. The multiplicity of guest proton signals shows that the capsule provides
      an asymmetric magnetic environment that persists on the (1)H NMR time scale. The
      encapsulation of these guests and common solvents suggests that the phenomenon of
      reversible encapsulation in chemistry may be a century old.

PMID- 16894155
TI  - Profile of Ewine F. van Dishoeck.

PMID- 16894156
TI  - Eastern North America as an independent center of plant domestication.
AB  - The status of eastern North America as an independent center of plant
      domestication has recently been called into question by a number of genetic and
      archaeological studies, which suggest that the region may not have witnessed the
      independent domestication of local crop plants, but rather may have been on the
      receiving end of domesticated crop plants introduced from Mexico. Here, I provide
      a synthesis of the currently available archaeological and genetic evidence from
      both eastern North America and Mexico regarding the spatial and temporal context
      of initial domestication of the four plant species identified as potential
      eastern North American domesticates: marshelder (Iva annua), chenopod
      (Chenopodium berlandieri), squash (Cucurbita pepo), and sunflower (Helianthus
      annuus). Genetic and archaeological evidence provides strong support for the
      independent domestication of all four of these plant species in the eastern
      United States and reconfirms the region as one of the world's independent centers
      of domestication.

PMID- 16894157
TI  - Agriculture: the selector of improbable mutations.

PMID- 16894159
TI  - A codon deletion confers resistance to herbicides inhibiting protoporphyrinogen
      oxidase.
AB  - Herbicides that act by inhibiting protoporphyrinogen oxidase (PPO) are widely
      used to control weeds in a variety of crops. The first weed to evolve resistance
      to PPO-inhibiting herbicides was Amaranthus tuberculatus, a problematic weed in
      the midwestern United States that previously had evolved multiple resistances to
      herbicides inhibiting two other target sites. Evaluation of a PPO-inhibitor
      resistant A. tuberculatus biotype revealed that resistance was a (incompletely)
      dominant trait conferred by a single, nuclear gene. Three genes predicted to
      encode PPO were identified in A. tuberculatus. One gene from the resistant
      biotype, designated PPX2L, contained a codon deletion that was shown to confer
      resistance by complementation of a hemG mutant strain of Escherichia coli grown
      in the presence and absence of the PPO inhibitor lactofen. PPX2L is predicted to
      encode both plastid- and mitochondria-targeted PPO isoforms, allowing a mutation
      in a single gene to confer resistance to two herbicide target sites. Unique
      aspects of the resistance mechanism include an amino acid deletion, rather than a
      substitution, and the dual-targeting nature of the gene, which may explain why
      resistance to PPO inhibitors has been rare.

PMID- 16894160
TI  - Crystallography on curved surfaces.
AB  - We study static and dynamical properties that distinguish 2D crystals constrained
      to lie on a curved substrate from their flat-space counterparts. A generic
      mechanism of dislocation unbinding in the presence of varying Gaussian curvature
      is presented in the context of a model surface amenable to full analytical
      treatment. We find that glide diffusion of isolated dislocations is suppressed by
      a binding potential of purely geometrical origin. Finally, the energetics and
      biased diffusion dynamics of point defects such as vacancies and interstitials
      are explained in terms of their geometric potential.

PMID- 16894158
TI  - Competitive recruitment of the periplasmic translocation portal TolB by a
      natively disordered domain of colicin E9.
AB  - The natively disordered N-terminal 83-aa translocation (T) domain of E group
      nuclease colicins recruits OmpF to a colicin-receptor complex in the outer
      membrane (OM) as well as TolB in the periplasm of Escherichia coli, the latter
      triggering translocation of the toxin across the OM. We have identified the 16
      residue TolB binding epitope in the natively disordered T-domain of the nuclease
      colicin E9 (ColE9) and solved the crystal structure of the complex. ColE9 folds
      into a distorted hairpin within a canyon of the six-bladed beta-propeller of
      TolB, using two tryptophans to bolt the toxin to the canyon floor and numerous
      intramolecular hydrogen bonds to stabilize the bound conformation. This mode of
      binding enables colicin side chains to hydrogen-bond TolB residues in and around
      the channel that runs through the beta-propeller and that constitutes the binding
      site of peptidoglycan-associated lipoprotein (Pal). Pal is a globular binding
      partner of TolB, and their association is known to be important for OM integrity.
      The structure is therefore consistent with translocation models wherein the
      colicin disrupts the TolB-Pal complex causing local instability of the OM as a
      prelude to toxin import. Intriguingly, Ca(2+) ions, which bind within the beta
      propeller channel and switch the surface electrostatics from negative to
      positive, are needed for the negatively charged T-domain to bind TolB with an
      affinity equivalent to that of Pal and competitively displace it. Our study
      demonstrates that natively disordered proteins can compete with globular proteins
      for binding to folded scaffolds but that this can require cofactors such as metal
      ions to offset unfavorable interactions.

PMID- 16894161
TI  - Ouabain affinity determining residues lie close to the Na/K pump ion pathway.
AB  - The Na/K pump establishes essential ion concentration gradients across animal
      cell membranes. Cardiotonic steroids, such as ouabain, are specific inhibitors of
      the Na/K pump. We exploited the marine toxin, palytoxin, to probe both the ion
      translocation pathway through the Na/K pump and the site of its interaction with
      ouabain. Palytoxin uncouples the pump's gates, which normally open strictly
      alternately, thus allowing both gates to sometimes be open, so transforming the
      pump into an ion channel. Palytoxin therefore permits electrophysiological
      analysis of even a single Na/K pump. We used outside-out patch recording of
      Xenopus alpha1beta3 Na/K pumps, which were made ouabain-resistant by point
      mutation, after expressing them in Xenopus oocytes. Endogenous, ouabain
      sensitive, Xenopus alpha1beta3 Na/K pumps were silenced by continuous exposure to
      ouabain. We found that side-chain charge of two residues at either end of the
      alpha subunit's first extracellular loop, known to make a major contribution to
      ouabain affinity, strongly influenced conductance of single palytoxin-bound pump
      channels by an electrostatic mechanism. The effects were mimicked by modification
      of cysteines introduced at those two positions with variously charged
      methanethiosulfonate reagents. The consequences of these modifications
      demonstrate that both residues lie in a wide vestibule near the mouth of the
      pump's ion pathway. Bound ouabain protects the site with the strongest influence
      on conductance from methanethiosulfonate modification, while leaving the site
      with the weaker influence unprotected. The results suggest a method for mapping
      the footprint of bound cardiotonic steroid on the extracellular surface of the
      Na/K pump.

PMID- 16894162
TI  - The essential GTPase YphC displays a major domain rearrangement associated with
      nucleotide binding.
AB  - The structure of a Bacillus subtilis YphC/GDP complex shows that it contains two
      GTPase domains that pack against a central domain whose fold resembles that of an
      RNA binding KH-domain. Comparisons of this structure to that of a homologue in
      Thermotoga maritima reveals a dramatic rearrangement in the position of the N
      terminal GTPase domain with a shift of up to 60 A and the formation of a totally
      different interface to the central domain. This rearrangement appears to be
      triggered by conformational changes of the switch II region in this domain in
      response to nucleotide binding. Modeling studies suggest that this motion
      represents transitions between the "on" and "off" states of the GTPase, the
      effect of which is to alternately expose and bury a positively charged face of
      the central domain that we suggest is involved in RNA recognition as part of the
      possible role of this enzyme in ribosome binding.

PMID- 16894163
TI  - Myosin-X is a molecular motor that functions in filopodia formation.
AB  - Despite recent progress in understanding lamellipodia extension, the molecular
      mechanisms regulating filopodia formation remain largely unknown. Myo10 is a
      MyTH4-FERM myosin that localizes to the tips of filopodia and is hypothesized to
      function in filopodia formation. To determine whether endogenous Myo10 is
      required for filopodia formation, we have used scanning EM to assay the numerous
      filopodia normally present on the dorsal surfaces of HeLa cells. We show here
      that siRNA-mediated knockdown of Myo10 in HeLa cells leads to a dramatic loss of
      dorsal filopodia. Overexpressing the coiled coil region from Myo10 as a dominant-
      negative also leads to a loss of dorsal filopodia, thus providing independent
      evidence that Myo10 functions in filopodia formation. We also show that
      expressing Myo10 in COS-7 cells, a cell line that normally lacks dorsal
      filopodia, leads to a massive induction of dorsal filopodia. Because the dorsal
      filopodia induced by Myo10 are not attached to the substrate, Myo10 can promote
      filopodia by a mechanism that is independent of substrate attachment. Consistent
      with this observation, a Myo10 construct that lacks the FERM domain, the region
      that binds to integrin, retains the ability to induce dorsal filopodia. Deletion
      of the MyTH4-FERM region, however, completely abolishes Myo10's filopodia
      promoting activity, as does deletion of the motor domain. Additional experiments
      on the mechanism of Myo10 action indicate that it acts downstream of Cdc42 and
      can promote filopodia in the absence of VASP proteins. Together, these data
      demonstrate that Myo10 is a molecular motor that functions in filopodia
      formation.

PMID- 16894164
TI  - The chemistry in circumstellar envelopes of evolved stars: following the origin
      of the elements to the origin of life.
AB  - Mass loss from evolved stars results in the formation of unusual chemical
      laboratories: circumstellar envelopes. Such envelopes are found around carbon-
      and oxygen-rich asymptotic giant branch stars and red supergiants. As the gaseous
      material of the envelope flows from the star, the resulting temperature and
      density gradients create a complex chemical environment involving hot,
      thermodynamically controlled synthesis, molecule "freeze-out," shock-initiated
      reactions, and photochemistry governed by radical mechanisms. In the
      circumstellar envelope of the carbon-rich star IRC+10216, >50 different chemical
      compounds have been identified, including such exotic species as C(8)H, C(3)S,
      SiC(3), and AlNC. The chemistry here is dominated by molecules containing long
      carbon chains, silicon, and metals such as magnesium, sodium, and aluminum, which
      makes it quite distinct from that found in molecular clouds. The molecular
      composition of the oxygen-rich counterparts is not nearly as well explored,
      although recent studies of VY Canis Majoris have resulted in the identification
      of HCO(+), SO(2), and even NaCl in this object, suggesting chemical complexity
      here as well. As these envelopes evolve into planetary nebulae with a hot,
      exposed central star, synthesis of molecular ions becomes important, as indicated
      by studies of NGC 7027. Numerous species such as HCO(+), HCN, and CCH are found
      in old planetary nebulae such as the Helix. This "survivor" molecular material
      may be linked to the variety of compounds found recently in diffuse clouds.
      Organic molecules in dense interstellar clouds may ultimately be traced back to
      carbon-rich fragments originally formed in circumstellar shells.

PMID- 16894165
TI  - Chemistry in low-mass protostellar and protoplanetary regions.
AB  - When interstellar clouds collapse to form new stars and planets, the surrounding
      gas and dust become part of the infalling envelopes and rotating disks, thus
      providing the basic material from which new solar systems are formed.
      Instrumentation to probe the chemistry in low-mass star-forming regions has only
      recently become available. The results of a systematic program to study the
      abundances in solar-mass protostellar and protoplanetary regions are presented.
      Surveys at submillimeter and infrared wavelengths reveal a rich chemistry,
      including simple and complex (organic) gases, ices, polycyclic aromatic
      hydrocarbons, and silicates. Each of these species traces different aspects of
      the physical and chemical state of the objects as they evolve from deeply
      embedded protostars to pre-main sequence stars with planet-forming disks.
      Quantitative information on temperatures, densities, and abundances is obtained
      through molecular excitation and radiative transfer models as well as from
      analysis of solid-state line profiles. The chemical characteristics are dominated
      by freeze-out in the coldest regions and ice evaporation in the warmer zones. In
      the surface layers of disks, UV radiation controls the chemistry. The importance
      of complementary laboratory experiments and calculations to obtain basic
      molecular data is emphasized.

PMID- 16894166
TI  - The galactic cosmic ray ionization rate.
AB  - The chemistry that occurs in the interstellar medium in response to cosmic ray
      ionization is summarized, and a review of the ionization rates that have been
      derived from measurements of molecular abundances is presented. The successful
      detection of large abundances of H(3)(+) in diffuse clouds and the recognition
      that dissociative recombination of H(3)(+) is fast has led to an upward revision
      of the derived ionization rates. In dense clouds the molecular abundances are
      sensitive to the depletion of carbon monoxide, atomic oxygen, nitrogen, water,
      and metals and the presence of large molecules and grains. Measurements of the
      relative abundances of deuterated species provide information about the ion
      removal mechanisms, but uncertainties remain. The models, both of dense and
      diffuse clouds, that are used to interpret the observations may be seriously
      inadequate. Nevertheless, it appears that the ionization rates differ in dense
      and diffuse clouds and in the intercloud medium.

PMID- 16894168
TI  - Interferometric observations of large biologically interesting interstellar and
      cometary molecules.
AB  - Interferometric observations of high-mass regions in interstellar molecular
      clouds have revealed hot molecular cores that have substantial column densities
      of large, partly hydrogen-saturated molecules. Many of these molecules are of
      interest to biology and thus are labeled "biomolecules." Because the clouds
      containing these molecules provide the material for star formation, they may
      provide insight into presolar nebular chemistry, and the biomolecules may provide
      information about the potential of the associated interstellar chemistry for
      seeding newly formed planets with prebiotic organic chemistry. In this overview,
      events are outlined that led to the current interferometric array observations.
      Clues that connect this interstellar hot core chemistry to the solar system can
      be found in the cometary detection of methyl formate and the interferometric maps
      of cometary methanol. Major obstacles to understanding hot core chemistry remain
      because chemical models are not well developed and interferometric observations
      have not been very sensitive. Differentiation in the molecular isomers
      glycolaldehdye, methyl formate, and acetic acid has been observed, but not
      explained. The extended source structure for certain sugars, aldehydes, and
      alcohols may require nonthermal formation mechanisms such as shock heating of
      grains. Major advances in understanding the formation chemistry of hot core
      species can come from observations with the next generation of sensitive, high
      resolution arrays.

PMID- 16894167
TI  - Mutational analysis of DJ-1 in Drosophila implicates functional inactivation by
      oxidative damage and aging.
AB  - Inherited mutations in PARK7, the gene encoding DJ-1, are associated with loss of
      protein function and early-onset parkinsonism. Like human DJ-1 (hDJ-1),
      Drosophila DJ-1b protects against oxidative insult and is modified with
      oxidation. We demonstrate that hDJ-1 rescues flies mutant for DJ-1b, and that a
      conserved cysteine residue in the fly protein (C104, analogous to C106 in hDJ-1)
      is critical for biological antioxidant function in vivo. Targeted mutagenesis
      suggests that modification of DJ-1b at this residue inactivates the protective
      activity of the protein against oxidative stress. Further studies show that DJ-1
      modification increases dramatically with age in flies, mice, and humans, with
      aged flies showing strikingly increased susceptibility to oxidative stress and
      markedly enhanced DJ-1b modification upon oxidative challenge. Overoxidation of
      DJ-1 with age and exposure to oxidative toxins may lead to inactivation of DJ-1
      function, suggesting a role in susceptibility to sporadic Parkinson's disease.

PMID- 16894170
TI  - Monte Carlo studies of surface chemistry and nonthermal desorption involving
      interstellar grains.
AB  - Although still poorly understood, the chemistry that occurs on the surfaces of
      interstellar dust particles profoundly affects the growth of molecules in the
      interstellar medium. The most important surface reaction is the conversion of
      atomic to molecular hydrogen, which is a precursor for all subsequent molecular
      development and which occurs both in diffuse and dense interstellar clouds.
      Another set of surface reactions produces icy mantles of many monolayers in cold
      and dense regions of the interstellar medium. The monolayers are dominated by
      water ice but also contain CO, CO(2), and occasionally methanol. In this work, we
      first review both our stochastic approach to the surface chemistry that can occur
      on small dust particles and how it has been applied to the problem of the
      formation of molecular hydrogen. This latter problem is strongly affected by the
      pulsed heating of smaller grains by photons. Photons are not the only source of
      pulsed heating; cosmic rays also can heat interstellar grains in a pulsed manner.
      Here, we calculate the heating by cosmic rays for different grain sizes and
      cosmic ray components. It is then shown that this mechanism is an important one
      for desorption of ice mantles.

PMID- 16894169
TI  - Detection of low-frequency lambda-doublet transitions of the free 12CH and 13CH
      radicals.
AB  - By Fourier transform microwave spectroscopy, lambda-doubling transitions of
      (12)CH and (13)CH in the lowest rotational levels of the X(2) product
      operator(1/2) ground state have been directly detected, which has not been done
      previously. For both radicals, hyperfine-split lines have been measured to an
      accuracy of better than 1 ppm between 3 and 15 GHz, an improvement of at least 2
      orders of magnitude over previous laboratory data. The measured frequencies have
      been combined with all previous data for CH and (13)CH in the v = 0 level of the
      X(2) product operator electronic state to determine improved hyperfine
      parameters. The production of CH from various gases also has been studied and,
      with methanol, the yield of CH relative to OH. Astronomical studies of CH in
      higher rotational levels and (13)CH can now be undertaken on the basis of the
      present work.

PMID- 16894171
TI  - Interstellar H(3)(+).
AB  - Protonated molecular hydrogen, H(3)(+), is the simplest polyatomic molecule. It
      is the most abundantly produced interstellar molecule, next only to H(2),
      although its steady state concentration is low because of its extremely high
      chemical reactivity. H(3)(+) is a strong acid (proton donor) and initiates chains
      of ion-molecule reactions in interstellar space thus leading to formation of
      complex molecules. Here, I summarize the understandings on this fundamental
      species in interstellar space obtained from our infrared observations since its
      discovery in 1996 and discuss the recent observations and analyses of H(3)(+) in
      the Central Molecular Zone near the Galatic center that led to a revelation of a
      vast amount of warm and diffuse gas existing in the region.

PMID- 16894172
TI  - Sex- and clock-controlled expression of the neuropeptide F gene in Drosophila.
AB  - Drosophila neuropeptide F (NPF), a homolog of vertebrate neuropeptide Y,
      functions in feeding and coordination of behavioral changes in larvae and in
      modulation of alcohol sensitivity in adults, suggesting diverse roles for this
      peptide. To gain more insight into adult-specific NPF neuronal functions, we
      studied how npf expression is regulated in the adult brain. Here, we report that
      npf expression is regulated in both sex-nonspecific and male-specific manners.
      Our data show that male-specific npf (ms-npf) expression is controlled by the
      transformer (tra)-dependent sex-determination pathway. Furthermore, fruitless,
      one of the major genes functioning downstream of tra, is apparently an upstream
      regulator of ms-npf transcription. Males lacking ms-npf expression (through
      tra(F)-mediated feminization) or npf-ablated male flies display significantly
      reduced male courtship activity, suggesting that one function of ms-npf neurons
      is to modulate fruitless-regulated sexual behavior. Interestingly, one of the ms
      npf neuronal groups belongs to the previously defined clock-controlling
      dorsolateral neurons. Such ms-npf expression in the dorsolateral neurons is
      absent in arrhythmic Clock(Jrk) and cycle(02) mutants, suggesting that npf is
      under dual regulation by circadian and sex-determining factors. Based on these
      data, we propose that NPF also plays a role in clock-controlled sexual dimorphism
      in adult Drosophila.

PMID- 16894173
TI  - Smallpox transmission and control: spatial dynamics in Great Britain.
AB  - Contingency planning for the possible deliberate reintroduction of smallpox has
      become a priority for many national public health organizations in recent years.
      We used an individual-based spatial model of smallpox transmission in Great
      Britain and census-derived journey-to-work data to accurately describe the
      spatiotemporal dynamics of an outbreak of smallpox in the community. A Markov
      chain Monte-Carlo algorithm was developed to generate sociospatial contact
      networks that were consistent with demographic and commuting data. We tested the
      sensitivity of model predictions to key epidemiological parameters before
      choosing three representative scenarios from within the range explored. We
      examined the spatiotemporal dynamics for these illustrative scenarios and
      assessed the efficacy of symptomatic case isolation, contact tracing with
      vaccination, and reactive regional mass vaccination as policy options for
      control. We conclude that case isolation and contact tracing with vaccination
      would be sufficient to halt ongoing transmission rapidly, unless policy
      effectiveness was compromised by resource or other constraints. A slight
      reduction in the expected size and duration of an outbreak could be achieved with
      regional mass vaccination, but these benefits are small and do not justify the
      high numbers of vaccine doses required and their associated negative side
      effects.

PMID- 16894174
TI  - Permanent carbon dioxide storage in deep-sea sediments.
AB  - Stabilizing the concentration of atmospheric CO(2) may require storing enormous
      quantities of captured anthropogenic CO(2) in near-permanent geologic reservoirs.
      Because of the subsurface temperature profile of terrestrial storage sites, CO(2)
      stored in these reservoirs is buoyant. As a result, a portion of the injected
      CO(2) can escape if the reservoir is not appropriately sealed. We show that
      injecting CO(2) into deep-sea sediments below [corrected] 3,000-m water depth and
      a few hundred meters of sediment provides permanent geologic storage even with
      large geomechanical perturbations. At the high pressures and low temperatures
      common in deep-sea sediments, CO(2) resides in its liquid phase and can be denser
      than the overlying pore fluid, causing the injected CO(2) to be gravitationally
      stable. Additionally, CO(2) hydrate formation will impede the flow of CO(2)(l)
      and serve as a second cap on the system. The evolution of the CO(2) plume is
      described qualitatively from the injection to the formation of CO(2) hydrates and
      finally to the dilution of the CO(2)(aq) solution by diffusion. If calcareous
      sediments are chosen, then the dissolution of carbonate host rock by the
      CO(2)(aq) solution will slightly increase porosity, which may cause large
      increases in permeability. Karst formation, however, is unlikely because total
      dissolution is limited to only a few percent of the rock volume. The total CO(2)
      storage capacity within the 200-mile economic zone of the U.S. coastline is
      enormous, capable of storing thousands of years of current U.S. CO(2) emissions.

PMID- 16894176
TI  - Archaeal nitrification in the ocean.
AB  - Marine Crenarchaeota are the most abundant single group of prokaryotes in the
      ocean, but their physiology and role in marine biogeochemical cycles are unknown.
      Recently, a member of this clade was isolated from a sea aquarium and shown to be
      capable of nitrification, tentatively suggesting that Crenarchaeota may play a
      role in the oceanic nitrogen cycle. We enriched a crenarchaeote from North Sea
      water and showed that its abundance, and not that of bacteria, correlates with
      ammonium oxidation to nitrite. A time series study in the North Sea revealed that
      the abundance of the gene encoding for the archaeal ammonia monooxygenase alfa
      subunit (amoA) is correlated with a decline in ammonium concentrations and with
      the abundance of Crenarchaeota. Remarkably, the archaeal amoA abundance was 1-2
      orders of magnitude higher than those of bacterial nitrifiers, which are commonly
      thought to mediate the oxidation of ammonium to nitrite in marine environments.
      Analysis of Atlantic waters of the upper 1,000 m, where most of the ammonium
      regeneration and oxidation takes place, showed that crenarchaeotal amoA copy
      numbers are also 1-3 orders of magnitude higher than those of bacterial amoA. Our
      data thus suggest a major role for Archaea in oceanic nitrification.

PMID- 16894175
TI  - Molecular and functional analysis of nicotinate catabolism in Eubacterium
      barkeri.
AB  - The anaerobic soil bacterium Eubacterium barkeri catabolizes nicotinate to
      pyruvate and propionate via a unique fermentation. A full molecular
      characterization of nicotinate fermentation in this organism was accomplished by
      the following results: (i) A 23.2-kb DNA segment with a gene cluster encoding all
      nine enzymes was cloned and sequenced, (ii) two chiral intermediates were
      discovered, and (iii) three enzymes were found, completing the hitherto unknown
      part of the pathway. Nicotinate dehydrogenase, a (nonselenocysteine) selenium
      containing four-subunit enzyme, is encoded by ndhF (FAD subunit), ndhS (2 x [2Fe
      2S] subunit), and by the ndhL/ndhM genes. In contrast to all enzymes of the
      xanthine dehydrogenase family, the latter two encode a two-subunit molybdopterin
      protein. The 6-hydroxynicotinate reductase, catalyzing reduction of 6
      hydroxynicotinate to 1,4,5,6-tetrahydro-6-oxonicotinate, was purified and shown
      to contain a covalently bound flavin cofactor, one [2Fe-2S](2+/1+) and two [4Fe
      4S](2+/1+) clusters. Enamidase, a bifunctional Fe-Zn enzyme belonging to the
      amidohydrolase family, mediates hydrolysis of 1,4,5,6-tetrahydro-6-oxonicotinate
      to ammonia and (S)-2-formylglutarate. NADH-dependent reduction of the latter to
      (S)-2-(hydroxymethyl)glutarate is catalyzed by a member of the 3
      hydroxyisobutyrate/phosphogluconate dehydrogenase family. A [4Fe-4S]-containing
      serine dehydratase-like enzyme is predicted to form 2-methyleneglutarate. After
      the action of the coenzyme B(12)-dependent 2-methyleneglutarate mutase and 3
      methylitaconate isomerase, an aconitase and isocitrate lyase family pair of
      enzymes, (2R,3S)-dimethylmalate dehydratase and lyase, completes the pathway.
      Genes corresponding to the first three enzymes of the E. barkeri nicotinate
      catabolism were identified in nine Proteobacteria.

PMID- 16894177
TI  - Finding neuroelectric activity under magnetic-field oscillations (NAMO) with
      magnetic resonance imaging in vivo.
AB  - Neuroimaging techniques are among the most important tools for investigating the
      function of the human nervous system and for improving the clinical diagnosis of
      neurological disorders. However, most commonly used techniques are limited by
      their invasiveness or their inability to accurately localize neural activity in
      space or time. Previous attempts at using MRI to directly image neuroelectric
      activity in vivo through the detection of magnetic field changes induced by
      neuronal currents have been challenging because of the extremely small signal
      changes and confounding factors such as hemodynamic modulations. Here we describe
      an MRI technique that uses oscillating magnetic field gradients to significantly
      amplify and detect the Lorentz effect induced by neuroelectric activity, and we
      demonstrate its effectiveness in imaging sensory nerve activation in vivo in the
      human median nerve during electrical stimulation of the wrist. This direct, real
      time, and noninvasive neuroimaging technique may potentially find broad
      applications in neurosciences.

PMID- 16894178
TI  - End-to-end distance distributions and intrachain diffusion constants in unfolded
      polypeptide chains indicate intramolecular hydrogen bond formation.
AB  - Characterization of the unfolded state is essential for the understanding of the
      protein folding reaction. We performed time-resolved FRET measurements to gain
      information on the dimensions and the internal dynamics of unfolded polypeptide
      chains. Using an approach based on global analysis of data obtained from two
      different donor-acceptor pairs allowed for the determination of distance
      distribution functions and diffusion constants between the chromophores. Results
      on a polypeptide chain consisting of 16 Gly-Ser repeats between the FRET
      chromophores reveal an increase in the average end-to-end distance from 18.9 to
      39.2 Angstrom between 0 and 8 M GdmCl. The increase in chain dimensions is
      accompanied by an increase in the end-to-end diffusion constant from (3.6 +/-
      1.0) x 10(-7) cm(2) s(-1) in water to (14.8 +/- 2.5) x 10(-7) cm(2) s(-1) in 8 M
      GdmCl. This finding suggests that intrachain interactions in water exist even in
      very flexible chains lacking hydrophobic groups, which indicates intramolecular
      hydrogen bond formation. The interactions are broken upon denaturant binding,
      which leads to increased chain flexibility and longer average end-to-end
      distances. This finding implies that rapid collapse of polypeptide chains during
      refolding of denaturant-unfolded proteins is an intrinsic property of polypeptide
      chains and can, at least in part, be ascribed to nonspecific intramolecular
      hydrogen bonding. Despite decreased intrachain diffusion constants, the
      conformational search is accelerated in the collapsed state because of shorter
      diffusion distances. The measured distance distribution functions and diffusion
      constants in combination with Szabo-Schulten-Schulten theory were able to
      reproduce experimentally determined rate constants for end-to-end loop formation.

PMID- 16894179
TI  - Stress and the suppression of subordinate reproduction in cooperatively breeding
      meerkats.
AB  - In many animal societies, dominant individuals monopolize reproduction, but the
      tactics they employ to achieve this are poorly understood. One possibility is
      that aggressive dominants render their subordinates infertile by inducing chronic
      physiological "stress." However, this hypothesis has been discarded largely for
      cooperatively breeding species, where reproductive monopolies are often extreme.
      Here we provide strong support for the stress-related suppression hypothesis in a
      cooperative mammal, the meerkat (Suricata suricatta). When pregnant, dominant
      females subject some subordinate females to escalating aggression, culminating in
      temporary evictions from the group. While evicted, subordinate females suffer
      chronic elevation of their glucocorticoid adrenal hormone levels, reproductive
      down-regulation (reduced pituitary sensitivity to gonadotropin-releasing
      hormone), reduced conception rates, and increased abortion rates. Rather than
      constantly harassing all subordinate females, dominants only become aggressive
      when pregnant themselves (when subordinate reproduction would otherwise conflict
      with their own) and target those females with whom reproductive conflict is most
      likely (older, pregnant, and more distantly related females). Our findings
      suggest that dominant female meerkats employ stressful evictions to suppress
      reproduction among their probable competitors, when attempting to breed
      themselves. Given the lack of evidence for stress-related suppression in other
      cooperative breeders to date, it is clear that social stress alone cannot account
      for the reproductive failure of subordinates across such societies. However, our
      findings raise the possibility that, in some cooperative breeders at least,
      dominants may employ stress-related suppression as a backup mechanism to guard
      against lapses in reproductive restraint by their subordinates.

PMID- 16894180
TI  - Neutrophils: are they hyperalgesic or anti-hyperalgesic?

PMID- 16894182
TI  - Role of human cytomegalovirus UL131A in cell type-specific virus entry and
      release.
AB  - The human cytomegalovirus (HCMV) genes UL128, UL130 and UL131A are essential for
      endothelial cell infection. Complementation of the defective UL131A gene of the
      non-endotheliotropic HCMV strain AD169 with wild-type UL131A in cis in an ectopic
      position restored endothelial cell tropism. The UL131A protein was found in
      virions in a complex with gH. Coinfection of fibroblasts with UL131A-negative and
      -positive viruses restored the endothelial cell tropism of UL131A-negative
      virions by complementing the virions with UL131A protein. Virus entry into
      endothelial cells, but not into fibroblasts, was blocked by an antipeptide
      antiserum to pUL131A. AD169, cis-complemented with wild-type UL131A, showed an
      impaired release of infectious particles from fibroblasts. A comparable defect in
      virus release was observed when UL131A was expressed ectopically in a virus
      background already expressing an intact copy of UL131A. In contrast, virus
      release from infected endothelial cells was not affected by UL131A. These data
      suggest a dual role for pUL131A in virus entry and virus exit from infected
      cells.

PMID- 16894183
TI  - Coronaviruses in bent-winged bats (Miniopterus spp.).
AB  - A novel group 1 coronavirus was previously identified in bent-winged bats
      (Miniopterus spp.). Here, results are described from our ongoing surveillance of
      these bats for coronaviruses. These findings show that group 1 coronaviruses are
      endemic in these bat populations in Hong Kong. Genetic analysis of these viruses
      indicates that there are at least four different, but closely related, group 1
      coronaviruses (bat-CoV 1A, 1B, HKU7 and HKU8) circulating in bent-winged bats.
      Phylogenetic analysis revealed that these group 1 bat coronaviruses have
      descended from a common ancestor and that these viruses have been established in
      these bats for a long period of time. These data provide a better understanding
      of the emergence and evolution of coronaviruses. Bat-CoV 1A and 1B were detected
      in apparently healthy Miniopterus magnater and Miniopterus pusillus,
      respectively, on repeated sampling occasions at a single habitat, suggesting that
      these viruses have established a persistent infection in these populations.

PMID- 16894184
TI  - A humanized murine monoclonal antibody protects mice either before or after
      challenge with virulent Venezuelan equine encephalomyelitis virus.
AB  - A humanized monoclonal antibody (mAb) has been developed and its potential to
      protect from or cure a Venezuelan equine encephalomyelitis virus (VEEV) infection
      was evaluated. The VEEV-neutralizing, protective murine mAb 3B4C-4 was humanized
      using combinatorial antibody libraries and phage-display technology. Humanized
      VEEV-binding Fabs were evaluated for virus-neutralizing capacity, then selected
      Fabs were converted to whole immunoglobulin (Ig) G1, and stable cell lines were
      generated. The humanized mAb Hy4-26C, designated Hy4 IgG, had virus-neutralizing
      capacity similar to that of 3B4C-4. Passive antibody protection studies with
      purified Hy4 IgG were performed in adult Swiss Webster mice. As little as 100 ng
      Hy4 IgG protected 90 % of mice challenged with 100 intraperitoneal (i.p.) mean
      morbidity (MD(50)) doses of virulent VEEV (Trinidad donkey) 24 h after antibody
      transfer; also, 500 mug Hy4 IgG protected 80 % of mice inoculated with 100
      intranasal MD(50) doses of VEEV. Moreover, 10 mug passive Hy4 IgG protected 70 %
      of mice from a VEEV challenge dose as great as 10(7) i.p. MD(50). Hy4 IgG also
      protected mice from challenge with another epizootic VEEV variety, 1C (P676).
      Importantly, therapeutic administration of the humanized mAb to mice already
      infected with VEEV cured 90 % of mice treated with Hy4 IgG within 1 h of VEEV
      inoculation and 75 % of mice treated 24 h after virus infection.

PMID- 16894185
TI  - Generation of an adenoviral vaccine vector based on simian adenovirus 21.
AB  - Adenoviral vectors can be used to generate potent humoral and cellular immune
      responses to transgene products. Use of adenoviral vectors based on non-human
      isolates may allow for their utilization in populations harbouring neutralizing
      antibodies to common human serotypes. A vector chimera was constructed using
      simian adenovirus 22 (a serotype belonging to the species Human adenovirus E) and
      simian adenovirus 21 (a serotype belonging to the species Human adenovirus B)
      expressing the Ebola (Zaire) virus glycoprotein (Ad C5/C1-ZGP). This chimeric
      adenovirus vector was used as a model to test its efficacy as a genetic vaccine
      and comparisons were made to a vector based on the commonly used human adenovirus
      C serotype 5 (Adhu5-ZGP). Ebola glycoprotein-specific T- and B-cell responses
      were measured in B10BR mice vaccinated with either Adhu5-ZGP or Ad C5/C1-ZGP
      vectors. Both vectors resulted in Ebola glycoprotein-specific gamma interferon
      expressing T cells, although the Ad C5/C1-ZGP vector appeared to induce lower
      frequencies with kinetics slower than those elicited by the Adhu5-ZGP vector. The
      total immunoglobulin G response to Ebola glycoprotein was similar in sera from
      mice vaccinated with either vector. Two rhesus macaques vaccinated with the Ad
      C5/C1-ZGP vector were found to mount T-cell and antibody responses to the Ebola
      glycoprotein. It was found that a single administration of the chimeric Ad C5/C1
      ZGP vector protected mice against a lethal challenge with a mouse-adapted strain
      of the Ebola (Zaire) virus.

PMID- 16894186
TI  - Role of the putative heparan sulfate glycosaminoglycan-binding site of the
      adenovirus type 5 fiber shaft on liver detargeting and knob-mediated retargeting.
AB  - Liver tropism hampers systemic administration of adenovirus in gene therapy and
      virotherapy. In consequence, tumour targeting requires the combination of capsid
      modifications that abrogate liver transduction and redirect adenoviral vectors to
      tumour cells. Coxsackievirus and adenovirus receptor (CAR), integrins and heparan
      sulfate glycosaminoglycans (HSG) are receptors involved in adenovirus type 5
      (Ad5) entry into cells. The in vitro and in vivo properties of Ad5 vectors unable
      to bind CAR, integrins and HSG with and without Arg-Gly-Asp (RGD) inserted at the
      HI loop of the fiber were studied. As was previously observed with CAR-ablated
      vectors, CAR and integrin double binding-ablated vectors transduced hepatocytes
      less efficiently in vitro but not in vivo. On the contrary, the role of HSG on
      Ad5 infectivity was evident in vitro only when CAR binding was abrogated, but the
      shaft mutation that ablated HSG binding on the background of a normal capsid was
      sufficient to abrogate liver transduction in vivo. The insertion of amino acids
      RGD at the HI loop in a shaft-mutated fiber only partially rescued integrin
      mediated infectivity. These results indicate that the shaft mutation precluded
      HSG binding and affected the structure of the fiber. The insertion of ligands at
      the hexon or protein IX may be required to benefit from the fiber shaft mutation
      detargeting properties.

PMID- 16894187
TI  - Analysis of the interaction between RGD-expressing adenovirus type 5 fiber knob
      domains and alphavbeta3 integrin reveals distinct binding profiles and
      intracellular trafficking.
AB  - Adenovirus (Ad) vectors are used widely for experimental and therapeutic gene
      transfer. Ad-mediated gene delivery is often inefficient and, thus, there is
      considerable interest in developing Ad vectors that overcome biological barriers
      to efficient virus uptake. For this strategy to succeed, it is imperative that
      the interaction between such Ad vectors and their novel receptors is well
      understood. In this study, three surface-exposed loops (HI, CD and IJ loops) on
      the Ad5 fiber knob domain were selected as sites for insertion of an alphavbeta3
      integrin-binding RGD sequence. Three RGD-containing Ad5 fiber knob-domain mutants
      were produced as recombinant proteins and all were shown to interact with soluble
      alphavbeta3 integrin by using biomolecular cell-free assays. Cell adsorption and
      subsequent internalization and intracellular trafficking of each of these
      proteins were assessed by confocal microscopy. Whilst the Ad5 fiber knob domain
      expressing the RGD sequence in the HI and CD loops bound with similar association
      and dissociation profiles, the fiber knob domain expressing the RGD sequence in
      the IJ loop bound with slower association and faster dissociation rates. By using
      molecular modelling, it was shown that the Ad5 fiber knob domain in which the RGD
      peptide was expressed in the IJ loop was only capable of binding to one
      alphavbeta3 integrin molecule per trimer. In contrast, fiber knob domains in
      which the RGD peptide was expressed in the HI and CD loops were capable of
      binding to one integrin molecule per monomer. These differences in the
      interactions between each mutant and alphavbeta3 may explain our observation that
      the three RGD-bearing Ad5 fiber knob domains demonstrated similar internalization
      rates, but distinct patterns of endosomal transport and escape.

PMID- 16894188
TI  - A molecular approach to the identification of cytotoxic T-lymphocyte epitopes
      within equine herpesvirus 1.
AB  - Equine herpesvirus 1 (EHV-1) causes respiratory and neurological disease and
      abortion in horses. Animals with high frequencies of cytotoxic T lymphocytes
      (CTL) show reduced severity of respiratory disease and frequency of abortion,
      probably by CTL-mediated control of cell-associated viraemia. This study aimed to
      identify CTL epitopes restricted by selected major histocompatibility complex
      (MHC) class I alleles expressed in the equine leukocyte antigen (ELA) A3
      haplotype. Effector CTL were induced from EHV-1-primed ponies and thoroughbreds
      with characterized MHC class I haplotypes and screened against P815 target cells
      transfected with selected EHV-1 genes and MHC class I genes. Targets that
      expressed EHV-1 gene 64 and the MHC B2 gene were lysed by effector CTL in a
      genetically restricted manner. There was no T-cell recognition of targets
      expressing either the MHC B2 gene and EHV-1 genes 2, 12, 14, 16, 35, 63 or 69, or
      the MHC C1 gene and EHV-1 genes 12, 14, 16 or 64. A vaccinia virus vector
      encoding gene 64 (NYVAC-64) was also investigated. Using lymphocytes from ELA-A3
      horses, the recombinant NYVAC-64 virus induced effector CTL that lysed EHV-1
      infected target cells; the recombinant virus also supplied a functional peptide
      that was expressed by target cells and recognized in an MHC-restricted fashion by
      CTL induced with EHV-1. This construct may therefore be used to determine the
      antigenicity of EHV-1 gene 64 for other MHC haplotypes. These techniques are
      broadly applicable to the identification of additional CTL target proteins and
      their presenting MHC alleles, not only for EHV-1, but for other equine viruses.

PMID- 16894189
TI  - The UL4 gene of pseudorabies virus encodes a minor infected-cell protein that is
      dispensable for virus replication.
AB  - Although homologues of the open reading frame (ORF) UL4 of herpes simplex virus 1
      (Human herpesvirus 1) have been found in the genomes of all hitherto-analysed
      alphaherpesviruses, little is known about their function. In a project to analyse
      systematically, in an isogenic and standardized assay system, the gene products
      of the alphaherpesvirus pseudorabies virus (PrV; Suid herpesvirus 1), the PrV UL4
      gene product was identified using a monospecific rabbit antiserum prepared
      against a bacterial fusion protein. Western blot and immunofluorescence analyses
      revealed that the 146 codon UL4 ORF of PrV was translated into a nuclear 15 kDa
      protein which was detectable from 6 h after infection of rabbit kidney cells, but
      was not found in purified virus particles. For functional analysis, a UL4
      negative virus recombinant (PrV-DeltaUL4F) was generated by mutagenesis of an
      infectious full-length clone of the PrV genome in E. coli. PrV-DeltaUL4F was
      replication-competent in rabbit kidney cells, and plaque formation was not
      affected by the mutation. However, maximum virus titres of PrV-DeltaUL4F were
      decreased about fivefold compared with wild-type PrV, and electron microscopy of
      infected cells demonstrated an impairment of release of mature virions. This
      growth defect of PrV-DeltaUL4F could be corrected completely by propagation in
      UL4-expressing cells. Correlating with the inconspicuous in vitro phenotype,
      neurovirulence of PrV-DeltaUL4F was also not affected significantly. Thus, UL4
      encodes a non-structural protein of PrV that enhances virion formation but is not
      essential for PrV replication in vitro or in vivo.

PMID- 16894190
TI  - Evidence of ancient papillomavirus recombination.
AB  - An open question amongst papillomavirus taxonomists is whether recombination has
      featured in the evolutionary history of these viruses. Since the onset of the
      global AIDS epidemic, the question is somewhat less academic, because immune
      compromised human immunodeficiency virus patients are often co-infected with
      extraordinarily diverse mixtures of human papillomavirus (HPV) types. It is
      expected that these conditions may facilitate the emergence of HPV recombinants,
      some of which might have novel pathogenic properties. Here, a range of rigorous
      analyses is applied to full-genome sequences of papillomaviruses to provide
      convincing statistical and phylogenetic evidence that evolutionarily relevant
      papillomavirus recombination can occur.

PMID- 16894191
TI  - A granule cell neuron-associated JC virus variant has a unique deletion in the
      VP1 gene.
AB  - The human polyomavirus JC (JCV) typically infects glial cells and is the
      aetiological agent of progressive multifocal leukoencephalopathy (PML), which
      occurs in immunosuppressed individuals. The full-length sequence of a granule
      cell neuron-tropic JCV variant, JCV(GCN1), associated with lytic infection of
      granule cell neurons and cerebellar atrophy in a human immunodeficiency virus
      infected patient with PML was determined and compared with the sequence of the
      JCV isolate from the classic PML lesions present in the hemispheric white matter
      of the same individual (JCV(HWM)). A unique deletion was found in the C terminus
      of the VP1 gene of JCV(GCN1), which encodes the major capsid protein, resulting
      in a frame shift and a total change of the C-terminal amino acid sequence of this
      protein. This deletion was not present in JCV(HWM), suggesting that this mutation
      may be instrumental in facilitating entry or replication of JCV into granule cell
      neurons.

PMID- 16894192
TI  - Cell death in bovine parvovirus-infected embryonic bovine tracheal cells is
      mediated by necrosis rather than apoptosis.
AB  - The helper-independent bovine parvovirus (BPV) was studied to determine its
      effect on host embryonic bovine tracheal (EBTr) cells: whether the ultimate
      outcome of infection results in apoptotic cell death or cell death by necrosis.
      Infected cells were observed for changes marking apoptosis. Observations of
      alterations in nuclear morphology, membrane changes, apoptotic body formation,
      membrane phosphatidylserine inversions, caspase activation and cell DNA laddering
      in infected cells were not indicative of apoptosis. On the other hand, at the end
      of the virus replication cycle, infected cells released viral haemagglutinin and
      infectious virus particles, as would be expected from cell membrane failure.
      Moreover, the infected cells released lactate dehydrogenase (LDH), release of
      which is a marker of necrosis. LDH release into the cell medium correlated
      directly with viral m.o.i. and time post-infection. Furthermore, assessment of
      mitochondrial dehydrogenase activity was consistent with cell death by necrosis.
      Taken together, these findings indicate that cell death in BPV-infected EBTr
      cells is due to necrosis, as defined by infected-cell membrane failure and
      release of the cell contents into the extracellular environment.

PMID- 16894193
TI  - Gene organization and complete sequence of the Hyphantria cunea
      nucleopolyhedrovirus genome.
AB  - The whole-genome sequence of the Hyphantria cunea nucleopolyhedrovirus (HycuNPV)
      was analysed. The entire nucleotide sequence of the HycuNPV genome was 132 959 bp
      long, with a G+C content of 45.1 mol%. A total of 148 open reading frames (ORFs)
      consisting of more than 50 aa were encoded by the genome. HycuNPV shares more
      than 122 ORFs with other lepidopteran group I NPVs, including Autographa
      californica MNPV, Bombyx mori NPV, Choristoneura fumiferana MNPV (CfMNPV),
      Choristoneura fumiferana defective NPV, Epiphyas postvittana MNPV and Orgyia
      pseudotsugata MNPV (OpMNPV). Six ORFs are identified as being unique to HycuNPV.
      Most of the HycuNPV ORFs showed higher similarity to CfMNPV and OpMNPV ORFs than
      to those of the other group I NPVs. HycuNPV encodes two conotoxin-like homologues
      (ctls), which are observed only in OpMNPV in group I NPVs. HycuNPV encodes three
      inhibitors of apoptosis (iaps), hycu-iap-1, hycu-iap-2 and hycu-iap-3, a feature
      that it shares only with CfMNPV. In addition, six homologous regions (hrs) are
      identified in the HycuNPV genome. These hrs are located in regions similar to
      those of the OpMNPV hrs, but different from most of the CfMNPV hrs. Based on the
      close phylogenetic relationship and conservation of group I NPV-specific genes,
      such as gp64, ie-2 and ptp-1, it is concluded that HycuNPV belongs to the group I
      NPVs and is most similar to CfMNPV or OpMNPV.

PMID- 16894194
TI  - Open reading frame 132 of Helicoverpa armigera nucleopolyhedrovirus encodes a
      functional per os infectivity factor (PIF-2).
AB  - Open reading frame 132 (Ha132) of Helicoverpa armigera nucleopolyhedrovirus
      (HearNPV) is a homologue of per os infectivity factor 2 (pif-2) of Spodoptera
      exigua multiple nucleopolyhedrovirus. Sequence analysis indicated that Ha132
      encoded a protein of 383 aa with a predicted molecular mass of 44.5 kDa.
      Alignment of HA132 and its baculovirus homologues revealed that HA132 was highly
      conserved among baculoviruses, with 14 absolutely conserved cysteine residues. RT
      PCR indicated that Ha132 was first transcribed at 24 h post-infection. Western
      blot analysis showed that a 43 kDa band was detectable in HearNPV-infected HzAM1
      cells from 36 h post-infection. Western blots also indicated that HA132 was a
      component of the occlusion-derived virus, but not of budded virus. Deletion of
      Ha132 from HearNPV abolished per os infectivity, but had no effect on the
      infectivity of the budded virus phenotype.

PMID- 16894195
TI  - L-SIGN (CD209L) isoforms differently mediate trans-infection of hepatoma cells by
      hepatitis C virus pseudoparticles.
AB  - L-SIGN is a C-type lectin that is expressed on liver sinusoidal endothelial
      cells. Capture of Hepatitis C virus (HCV) by this receptor results in trans
      infection of hepatoma cells. L-SIGN alleles have been identified that encode
      between three and nine tandem repeats of a 23 residue stretch in the
      juxtamembrane oligomerization domain. Here, it was shown that these repeat-region
      isoforms are expressed at the surface of mammalian cells and variably bind HCV
      envelope glycoprotein E2 and HCV pseudoparticles. Differences in binding were
      reflected in trans-infection efficiency, which was highest for isoform 7 and
      lowest for isoform 3. These findings provide a molecular mechanism whereby L-SIGN
      polymorphism could influence the establishment and progression of HCV infection.

PMID- 16894196
TI  - High-density lipoproteins reduce the neutralizing effect of hepatitis C virus
      (HCV)-infected patient antibodies by promoting HCV entry.
AB  - The neutralizing activity of anti-hepatitis C virus (HCV) antibodies is
      attenuated by a factor present in human sera, which has been proposed to be high
      density lipoproteins (HDLs). HDLs have also been shown to facilitate the entry of
      HCV pseudoparticles (HCVpp) into target cells. Here, the aim of the study was to
      determine whether HDL-mediated facilitation of HCVpp and infectious HCV (HCVcc)
      entry and attenuation of neutralization are two related phenomena. The data
      indicated that HDLs attenuate neutralization at a constant rate. In addition, as
      for HDL-mediated facilitation of HCVpp entry, attenuation of neutralization
      depended on the expression of the scavenger receptor BI (SR-BI) and its selective
      lipid-uptake function. Finally, kinetic experiments showed that HDL-mediated
      facilitation of HCVpp entry is more rapid than virus neutralization. Altogether,
      these observations indicate that HCV is exploiting the physiological activity of
      SR-BI for promoting its entry into target cells, which consequently also protects
      the virus against neutralizing antibodies.

PMID- 16894197
TI  - Entry of hepatitis C virus pseudotypes into primary human hepatocytes by clathrin
      dependent endocytosis.
AB  - Hepatitis C virus (HCV) is a major cause of chronic hepatitis worldwide. Studies
      of the early steps of HCV infection have been hampered by the lack of convenient
      in vitro or in vivo models. Although several cell-surface molecules that mediate
      the binding of HCV envelope proteins to target cells have been identified,
      mechanisms of viral entry into human hepatocytes are still poorly understood.
      Vesicular stomatitis virus/HCV pseudotyped viruses expressing the HCV envelope
      glycoproteins on the viral envelope were generated and it was found that their
      entry into human hepatocytes required co-expression of E1 and E2 on the
      pseudotype surface. Neutralization of pseudotype infection by anti-HCV antibodies
      suggested that cellular entry was mediated by HCV envelope glycoproteins and by
      previously characterized cell-surface molecules, including CD81. An entry assay
      based on the release of a fluorochrome from labelled HCV pseudotypes provided
      evidence for a pH-dependent fusion of the pseudotype envelope with a cellular
      compartment. By using a panel of endocytosis inhibitors, it is postulated that
      penetration of HCV into primary cultures of hepatocytes takes place by clathrin
      mediated endocytosis.

PMID- 16894198
TI  - Comparative analysis reveals no consistent association between the secondary
      structure of the 3'-untranslated region of dengue viruses and disease syndrome.
AB  - A comparative analysis was performed of the 3'-untranslated region (UTR) of
      Dengue virus (DENV) sampled from Bangkok, Thailand, over a 30 year period and
      representing all four serotypes. Considerable genetic variation was observed both
      within and among serotypes. Notably, a full-length version of the critical 3'
      long stable hairpin structure was absent from some isolates, suggesting the
      occurrence of complex structural interactions within the 3'-UTR, including the
      influence of upstream mutations. The Thai sequences were then combined with 61
      globally sampled isolates of DENV taken from patients with either dengue fever or
      severe dengue disease. No consistent association was found between 3'-UTR
      secondary structure and the clinical outcome of DENV infection, although some
      evidence for a trend in this direction was observed in DENV-2. It was concluded
      that the 3'-UTR is not the sole determinant of DENV virulence in nature, although
      variation in secondary structure may greatly influence viral fitness.

PMID- 16894199
TI  - Dengue virus NS4B interacts with NS3 and dissociates it from single-stranded RNA.
AB  - Dengue virus, a member of the family Flaviviridae of positive-strand RNA viruses,
      has seven non-structural proteins: NS1, NS2A, NS2B, NS3, NS4A, NS4B and NS5.
      Except for enzymic activities contained within NS3 and NS5, the roles of the
      other proteins in virus replication and pathogenesis are not well defined. In
      this study, a physical interaction between NS4B and the helicase domain of NS3
      was identified by using a yeast two-hybrid assay. This interaction was further
      confirmed by biochemical pull-down and immunoprecipitation assays, both with
      purified proteins and with dengue virus-infected cell lysates. NS4B co-localized
      with NS3 in the perinuclear region of infected human cells. Furthermore, NS4B
      dissociated NS3 from single-stranded RNA and consequently enhanced the helicase
      activity of NS3 in an in vitro unwinding assay. These results suggest that NS4B
      modulates dengue virus replication via its interaction with NS3.

PMID- 16894200
TI  - The 3' untranslated regions of Kamiti River virus and Cell fusing agent virus
      originated by self-duplication.
AB  - Previously, it was shown that the 3' untranslated region (3'UTR) of Kamiti River
      virus (KRV) is nearly twice as long as the 3'UTR of other flaviviruses (1208
      nucleotides compared with 730 nucleotides for the longest 3'UTR of any virus in
      the Tick-borne encephalitis virus species). Additionally, KRV and the closely
      related Cell fusing agent virus (CFAV) were shown to contain two short, almost
      perfect repeat sequences of 67 nucleotides. However, the construction of a robust
      comparative nucleotide alignment has now revealed that the double-length 3'UTR
      and the direct repeats resulted from the virtually complete duplication of a
      primordial KRV 3'UTR. We also propose that the CFAV 3'UTR was derived from a KRV
      like precursor sequence with a large deletion that nevertheless preserved the two
      direct repeat sequences. These data provide new insights into the evolution of
      the flavivirus 3'UTR.

PMID- 16894201
TI  - Characterization of norovirus 3Dpol RNA-dependent RNA polymerase activity and
      initiation of RNA synthesis.
AB  - Norovirus (NV) 3D(pol) is a non-structural protein predicted to play an essential
      role in the replication of the NV genome. In this study, the characteristics of
      NV 3D(pol) activity and initiation of RNA synthesis have been examined in vitro.
      Recombinant NV 3D(pol), as well as a 3D(pol) active-site mutant were expressed in
      Escherichia coli and purified. NV 3D(pol) was able to synthesize RNA in vitro and
      displayed flexibility with respect to the use of Mg(2+) or Mn(2+) as a cofactor.
      NV 3D(pol) yielded two different products when incubated with synthetic RNA in
      vitro: (i) a double-stranded RNA consisting of two single strands of opposite
      polarity or (ii) the single-stranded RNA template labelled at its 3' terminus by
      terminal transferase activity. Initiation of RNA synthesis occurred de novo
      rather than by back-priming, as evidenced by the fact that the two strands of the
      double-stranded RNA product could be separated, and by dissociation in time
      course analysis of terminal transferase and RNA synthesis activities. In
      addition, RNA synthesis was not affected by blocking of the 3' terminus of the
      RNA template by a chain terminator, sustaining de novo initiation of RNA
      synthesis. NV 3D(pol) displays in vitro properties characteristic of RNA
      dependent RNA polymerases, allowing the implementation of this in vitro enzymic
      assay for the development and validation of antiviral drugs against NV, a so far
      non-cultivated virus and an important human pathogen.

PMID- 16894202
TI  - Proteome alterations in human host cells infected with coxsackievirus B3.
AB  - Coxsackievirus B3 (CVB3) is a common factor in human myocarditis. The interplay
      between host factors and virus components is crucial for the fate of the infected
      cells. Despite that, host protein responses, which characterize CVB3-induced
      diseases, have not yet been determined in detail. To investigate the nature of
      modified protein patterns in infected human cells compared with uninfected cells,
      two-dimensional gel electrophoresis in combination with matrix-assisted laser
      desorption/ionization-mass spectrometry were used. The regulated proteins, e.g.
      nucleophosmin (nucleolar protein B23), lamin, the RNA-binding protein UNR and the
      p38 mitogen-activated protein kinase, were sorted according to their functional
      groups and interpreted in the context of the myocarditis process.

PMID- 16894203
TI  - Influenza A virus NS1 protein does not suppress RNA interference in mammalian
      cells.
AB  - Influenza A virus NS1 protein has been shown to suppress RNA interference (RNAi)
      in plants and Drosophila. Although it has not been demonstrated experimentally,
      NS1 has also been thought to inhibit RNAi in mammals as well as being an
      antagonist of interferon. In this study, the influence of NS1 protein from
      influenza virus strain A/WSN/33 on RNAi in mammalian cells was investigated.
      While transiently or stably expressed NS1 was fully competent to inhibit the
      interferon pathway in cultured cells, it did not suppress RNAi-mediated silencing
      of different reporter genes. These findings imply a significant difference in
      RNAi mechanism between mammals and plants.

PMID- 16894204
TI  - In vivo correlates of infectious salmon anemia virus pathogenesis in fish.
AB  - The phenotypic correlates of pathogenicity for Infectious salmon anemia virus
      (ISAV) in salmonid fishes have not been thoroughly studied to date. In this
      study, a comparison was made of 13 different strains of ISAV, isolated from
      different geographical regions between 1997 and 2004, for their infectivity in
      three fish species [Atlantic salmon (Salmo salar), coho salmon (Oncorhynchus
      kisutch) and rainbow trout (Oncorhynchus mykiss)]. When the different virus
      isolates were used at an approximate inoculum dose of 10(6) TCID(50) in 0.2 ml
      per fish, it was found that the most virulent strains had an acute mortality
      phase in Atlantic salmon that started at 10-13 days post-inoculation and lasted
      for 9-15 days with a cumulative mortality of >/=90 %. These highly pathogenic
      strains also caused low mortality in rainbow trout, albeit later in infection.
      Viruses with a more delayed or protracted mortality phase resulting in cumulative
      mortalities of 50-89 % in Atlantic salmon were considered to be of intermediate
      pathogenicity and isolates with cumulative mortalities of </=49 % were considered
      to be of low pathogenicity. On this basis, three of the ISAV isolates showed a
      high-, eight an intermediate- and two a low-pathogenicity phenotype in Atlantic
      salmon. Coho salmon were resistant to all ISAV isolates. These results confirmed
      that there is variation in pathogenicity among ISAV strains for Atlantic salmon
      and rainbow trout, and that other salmonid species such as coho salmon can carry
      highly pathogenic strains of ISAV without showing signs of disease. The
      identified pathogenicity phenotypes may aid in the identification of molecular
      markers of ISAV virulence.

PMID- 16894205
TI  - Inhibition of vesicular stomatitis virus infection in epithelial cells by alpha
      interferon-induced soluble secreted proteins.
AB  - Interferons (IFNs) are potent antiviral cytokines that inhibit infection by a
      wide spectrum of viruses by activating the Janus kinase/signal transducers and
      activators of transcription (JAK/STAT) pathway. Several IFN-induced antiviral
      proteins including 2',5'-oligoadenylate synthetase, dsRNA-activated protein
      kinase and Mx play a critical role in conferring the antiviral properties of IFN.
      However, studies have shown that additional antiviral factors are involved in
      addition to these proteins during IFN-mediated antiviral action. In an effort to
      characterize these novel antiviral factors, the antiviral mechanism of alpha IFN
      (IFN-alpha) against vesicular stomatitis virus (VSV) was investigated in human
      lung epithelial A549 cells. These studies demonstrated that soluble secreted
      antiviral proteins as the constituents of conditioned medium prepared from IFN
      alpha-treated cells reduced VSV infectivity by more than 2 logs, compared with a
      4 log inhibition observed following treatment of cells with IFN-alpha. The
      antiviral mechanism of these secreted proteins appeared to act at the level of
      cellular entry of VSV. Interestingly, the IFN-alpha-induced antiviral proteins
      were secreted independently of STAT1 (an essential component of the JAK/STAT
      pathway), demonstrating that the release of such extracellular soluble antiviral
      proteins from cells may represent an alternative mechanism of the antiviral
      defence strategy of IFN towards VSV infection.

PMID- 16894206
TI  - Lyssavirus infection activates interferon gene expression in the brain.
AB  - To investigate the innate immune response within the brain to lyssavirus
      infection, key transcripts indicative of innate defences were measured in a mouse
      model system. Following infection with Rabies virus, transcript levels for type 1
      interferons (IFN-alpha and -beta), the inflammatory mediator interleukin 6 (IL-6)
      and the antiviral protein Mx1 increased in the brains of mice. Intracranial
      inoculation resulted in the early detection of virus replication and rapid
      expression within the brain of the innate immune response genes. Transcripts for
      type 1 IFNs declined as the disease progressed. Peripheral, extraneural
      inoculation delayed the host response until virus entered the brain, but then
      resulted in a large increase in the level of IFN-beta, IL-6 and Mx1 transcripts.
      Induction of this response was also observed following infection with the related
      European bat lyssaviruses, a group of zoonotic viruses capable of causing fatal,
      rabies-like disease in mammalian species.

PMID- 16894207
TI  - Gag-Pol bearing a reverse transcriptase drug-resistant mutation influences viral
      genomic RNA incorporation into human immunodeficiency virus type 1 particles.
AB  - The unspliced human immunodeficiency virus type 1 (HIV-1) RNA is both the
      messenger for Gag and Gag-Pol and the viral genomic RNA (vRNA) that is packaged
      into the virion. Although Gag alone is sufficient for the incorporation of vRNA
      into virus particles, Gag-Pol molecules play an important role in vRNA
      dimerization and virion maturation. Here, a cis model for vRNA packaging was
      demonstrated, in which nascent Gag-Pol molecules were preferentially co
      encapsulated with their cognate RNA used as the template. Genome-incorporation
      frequencies were evaluated for two distinct HIV-1 proviral clones differing in
      their ability to respond to nevirapine (NVP) treatment in one round of infection.
      It was shown that, under NVP selection, there was a twofold-higher incorporation
      of vRNAs and integration of provirus genome carrying NVP resistance when compared
      with the wild-type counterpart. Although cis incorporation has been already
      demonstrated for Gag, the novelty of these findings is that newly acquired
      resistant mutations in Gag-Pol will select their specific genomic RNA during
      virus replication, thus rapidly increasing the chance of the emergence of
      resistant viruses during the course of anti-retroviral treatment.

PMID- 16894208
TI  - Transmission of Moloney murine leukemia virus (ts-1) by breast milk.
AB  - A murine model has been developed to study maternal transmission of the
      temperature-sensitive Moloney murine leukemia virus (ts-1). The goal of this
      study was to confirm early and late mother-to-offspring transmission of the virus
      and demonstrate transmission via breast milk. A series of six experiments was
      performed using six groups of BALB/c mice. Group 1 consisted of pups born to ts-1
      infected mothers removed at birth to suckle from surrogate uninfected mothers.
      Groups 2 and 5 consisted of pups born to ts-1-infected mothers that suckled from
      ts-1-infected mothers (surrogate and biological). Group 3 consisted of non
      infected pups removed at birth to suckle from ts-1-infected mothers. Groups 4 and
      6 consisted of non-infected pups suckled from non-infected mothers. The combined
      in utero, intrapartum and breast-milk infection rate was 100 % to the offspring
      (groups 2 and 5). The in utero to early post-partum group (group 1) had an
      infection rate of 78 %. Breast milk alone (group 3) resulted in a 97 % infection
      rate. Control groups (groups 4 and 6) had a 0 % infection rate. The relative
      frequency of maternal CD4(+) cells in peripheral blood mononuclear cells was
      consistently lower in infected mothers, whilst offspring did not show a
      significant decrease in CD4(+) frequency. Pups infected via breast milk had a
      lower CD4(+) frequency (group 3) than those infected by the uterine and/or
      intrapartum route (group 1). Breast milk from ts-1-infected mothers appears to be
      highly infectious for neonatal BALB/c mice.

PMID- 16894209
TI  - E (XSR) element contributes to the oncogenicity of Avian leukosis virus (subgroup
      J).
AB  - Among the six subgroups of Avian leukosis virus (ALV) that infect chickens,
      subgroup J (ALV-J) was isolated from meat-type chickens where it predominantly
      induces myeloid leukosis (ML) and erythroblastosis (EB). The sequence of HPRS
      103, the ALV-J prototype virus, shows several distinct features, one of which is
      the presence of a distinct hairpin stem-loop structure called the E (also called
      XSR) element in the 3' untranslated region. In order to determine the role of the
      E element in ALV-induced pathogenicity, a comparison was made of the oncogenicity
      of viruses derived from the provirus clones of parental and E element-deleted
      HPRS-103 viruses in two genetically distinct lines of birds. In line 15I birds,
      deletion of the E element had profound effects on virus replication in vivo, as
      only 55 % of birds showed evidence of infection, compared with 100 % infection by
      the parental virus. Furthermore, none of the line 15I birds infected with this
      virus developed tumours, indicating that the E element does contribute to the
      oncogenicity of the virus. On the other hand, deletion of the E element had only
      a marginal effect on the incidence of tumours in line 0 birds. These results
      indicate that, although the E element per se is not absolutely essential for
      tumour induction by this subgroup of viruses, it does contribute to oncogenicity
      in certain genetic lines of chicken.

PMID- 16894210
TI  - An internal ribosome entry site located upstream of the crucifer-infecting
      tobamovirus coat protein (CP) gene can be used for CP synthesis in vivo.
AB  - It was previously shown that, unlike the type member of the genus Tobamovirus
      (TMV U1), a crucifer-infecting tobamovirus (crTMV) contains a 148 nt internal
      ribosome entry site (IRES)(CP,148)(CR) upstream of the coat protein (CP) gene.
      Here, viral vectors with substitutions in the stem-loop (SL) region of CP
      subgenomic promoters (TMV U1-CP-GFP/SL-mut and crTMV-CP-GFP/SL-mut) were
      constructed and the levels of CP synthesis in agroinoculation experiments were
      compared. No CP-GFP (green fluorescent protein) synthesis was detected in
      Nicotiana benthamiana leaves inoculated with TMV U1-CP-GFP/SL-mut, whereas a
      small amount of CP-GFP synthesis was obtained in crTMV-CP-GFP/SL-mut-injected
      leaves. Northern blots proved that both promoters were inactive. It could be
      hypothesized that IRES-mediated early production of the CP by crTMV is needed for
      realization of its crucifer-infecting capacity.

PMID- 16894211
TI  - Domains of tobacco mosaic virus movement protein essential for its membrane
      association.
AB  - A series of deletion mutants of tobacco mosaic virus movement protein (TMV-MP)
      was used to identify domains of the protein necessary for membrane association. A
      membrane fraction was isolated from tobacco BY-2 protoplasts infected with wild
      type and mutant TMV that produce MP carrying a 3 aa deletion. Deletions that
      affected membrane association were clustered around the two major hydrophobic
      regions of MP that are predicted to be transmembrane. Deletions in other
      hydrophobic regions also reduced membrane association. In addition, a non
      functional mutant of MP, in which one of the known phosphorylation sites was
      eliminated, was not associated with cellular membranes, while a functional second
      site revertant restored membrane association. This indicates that MP function
      requires interaction with membrane; however, membrane association was not
      sufficient for function. Results are consistent with the hypothesis that TMV-MP
      is an integral or tightly associated membrane protein that includes two
      hydrophobic transmembrane domains.

PMID- 16894212
TI  - Permeabilized mammalian cells as an experimental system for nuclear import of
      geminiviral karyophilic proteins and of synthetic peptides derived from their
      nuclear localization signal regions.
AB  - The plant-infecting geminiviruses deliver their genome and viral proteins into
      the host cell nucleus. Members of the family Geminiviridae possess either a
      bipartite genome composed of two approximately 2.6 kb DNAs or a monopartite
      genome of approximately 3.0 kb DNA. The bipartite genome of Bean dwarf mosaic
      virus (BDMV) encodes several karyophilic proteins, among them the capsid protein
      (CP) and BV1 (nuclear shuttle protein). A CP is also encoded by the monopartite
      genome of Tomato yellow leaf curl virus (TYLCV). Here, an in vitro assay system
      was used for direct demonstration of nuclear import of BDMV BV1 and TYLCV CP, as
      well as synthetic peptides containing their putative nuclear localization signals
      (NLSs). Full-length recombinant BDMV BV1 and TYLCV CP mediated import of
      conjugated fluorescently labelled BSA molecules into nuclei of permeabilized
      mammalian cells. Fluorescently labelled and biotinylated BSA conjugates bearing
      the synthetic peptides containing aa 3-20 of TYLCV CP (CP-NLS) or aa 84-106 of
      BDMV BV1 (BV1-NLS) were also imported into the nuclei of permeabilized cells.
      This import was blocked by the addition of unlabelled BSA-NLS peptide conjugates
      or excess unlabelled free NLS peptides. The CP- and BV1-NLS peptides also
      mediated nuclear import of fluorescently labelled BSA molecules into the nuclei
      of microinjected mesophyll cells of Nicotiana benthamiana leaves, demonstrating
      their biological function in intact plant tissue. BV1-NLS and CP-NLS were shown
      to mediate specific binding to importin alpha, both in vitro and in vivo. These
      results are consistent with a common nuclear-import pathway for CP and BV1,
      probably via importin alpha.

PMID- 16894213
TI  - Complete nucleotide sequence, genomic organization and phylogenetic analysis of
      Citrus leprosis virus cytoplasmic type.
AB  - The complete nucleotide sequence of the genomic RNA 1 (8745 nt) and RNA 2 (4986
      nt) of Citrus leprosis virus cytoplasmic type (CiLV-C) was determined using
      cloned cDNA. RNA 1 contains two open reading frames (ORFs), which correspond to
      286 and 29 kDa proteins. The 286 kDa protein is a polyprotein putatively involved
      in virus replication, which contains four conserved domains: methyltransferase,
      protease, helicase and polymerase. RNA 2 contains four ORFs corresponding to 15,
      61, 32 and 24 kDa proteins, respectively. The 32 kDa protein is apparently
      involved in cell-to-cell movement of the virus, but none of the other putative
      proteins exhibit any conserved domain. The 5' regions of the two genomic RNAs
      contain a 'cap' structure and poly(A) tails were identified in the 3'-terminals.
      Sequence analyses and searches for structural and non-structural protein
      similarities revealed conserved domains with members of the genera Furovirus,
      Bromovirus, Tobravirus and Tobamovirus, although phylogenetic analyses strongly
      suggest that CiLV-C is a member of a distinct, novel virus genus and family, and
      definitely demonstrate that it does not belong to the family Rhabdoviridae, as
      previously proposed. Based on these results it was proposed that Citrus leprosis
      virus be considered as the type member of a new genus of viruses, Cilevirus.

PMID- 16894214
TI  - Potato virus X RNA-mediated assembly of single-tailed ternary 'coat protein-RNA
      movement protein' complexes.
AB  - Different models have been proposed for the nature of the potexvirus transport
      form that moves from cell to cell over the infected plant: (i) genomic RNA moves
      as native virions; or (ii) in vitro-assembled non-virion ribonucleoprotein (RNP)
      complexes consisting of viral RNA, coat protein (CP) and movement protein (MP),
      termed TGBp1, serve as the transport form in vivo. As the structure of these RNPs
      has not been elucidated, the products assembled in vitro from potato virus X
      (PVX) RNA, CP and TGBp1 were characterized. The complexes appeared as single
      tailed particles (STPs) with a helical, head-like structure composed of CP
      subunits located at the 5'-proximal region of PVX RNA; the TGBp1 was bound to the
      terminal CP molecules of the head. Remarkably, no particular non-virion RNP
      complexes were observed. These data suggest that the CP-RNA interactions
      resulting in head formation prevailed over TGBp1-RNA binding upon STP assembly
      from RNA, CP and TGBp1. STPs could be assembled from the 5' end of PVX RNA and CP
      in the absence of TGBp1. The translational ability of STPs was characterized in a
      cell-free translation system. STPs lacking TGBp1 were entirely non-translatable;
      however, they were rendered translatable by binding of TGBp1 to the end of the
      head. It is suggested that the RNA-mediated assembly of STPs proceeds via two
      steps. Firstly, non-translatable CP-RNA STPs are produced, due to encapsidation
      of the 5'-terminal region. Secondly, the TGBp1 molecules bind to the end of a
      polar head, resulting in conversion of the STPs into a translatable form.

PMID- 16894215
TI  - Random mutagenesis of wheat streak mosaic virus HC-Pro: non-infectious
      interfering mutations in a gene dispensable for systemic infection of plants.
AB  - Mutations within the HC-Pro coding region of Wheat streak mosaic virus (WSMV)
      were introduced by misincorporation during PCR and evaluated for phenotype within
      the context of an infectious clone. Nine synonymous substitutions and 15 of 25
      non-synonymous substitutions had no phenotypic effect. Four non-synonymous
      substitutions, including one that reverted consistently to wild type, resulted in
      attenuated systemic infection. Six non-synonymous substitutions and one nonsense
      substitution abolished systemic infectivity. Mutants bearing the GUS reporter
      gene were evaluated for the ability to establish primary infection foci. All
      attenuated mutants and two systemic infection-deficient mutants produced
      localized regions of GUS expression on inoculated leaves 3 days post-inoculation.
      In vitro assays revealed that mutants able to establish infection foci retained
      HC-Pro proteinase activity. Among mutants unable to establish infection foci, HC
      Pro proteinase activity was retained, reduced or absent. As a complete HC-Pro
      deletion mutant can infect plants systemically, certain substitutions in this
      dispensable gene probably prevented infection of WSMV via interference.

PMID- 16894216
TI  - In vitro-reassembled plant virus-like particles for loading of polyacids.
AB  - The coat protein (CP) of certain plant viruses may reassemble into empty virus
      like particles (VLPs) and these protein cages may serve as potential drug
      delivery platforms. In this paper, the production of novel VLPs from the Hibiscus
      chlorotic ringspot virus (HCRSV) is reported and the capacity to load foreign
      materials was characterized. VLPs were readily produced by destabilizing the
      HCRSV in 8 M urea or Tris buffer pH 8, in the absence of calcium ions, followed
      by removal of viral RNA by ultrahigh-speed centrifugation and the reassembly of
      the CP in sodium acetate buffer pH 5. The loading of foreign materials into the
      VLPs was dependent on electrostatic interactions. Anionic polyacids, such as
      polystyrenesulfonic acid and polyacrylic acid, were successfully loaded but
      neutrally charged dextran molecules were not. The molecular-mass threshold for
      the polyacid cargo was about 13 kDa, due to the poor retention of smaller
      molecules, which readily diffused through the holes between the S domains present
      on the surface of the VLPs. These holes precluded the entry of large molecules,
      but allowed smaller molecules to enter or exit. The polyacid-loaded VLPs had
      comparable size, morphology and surface-charge density to the native HCRSV, and
      the amount of polyacids loaded was comparable to the weight of the native genomic
      materials. The conditions applied to disassembly-reassembly of the virions did
      not change the structural conformation of the CP. HCRSV-derived VLPs may provide
      a promising nano-sized protein cage for delivery of anionic drug molecules.

PMID- 16894217
TI  - A GCUA tetranucleotide loop found in the poliovirus oriL by in vivo SELEX
      (un)expectedly forms a YNMG-like structure: Extending the YNMG family with GYYA.
AB  - The cloverleaf structure in the 5'-untranslated region of enterovirus RNA that
      regulates viral RNA replication contains an evolutionarily conserved YNMG
      tetraloop closed by a Y-G base pair. This loop is believed to interact
      specifically with the viral protease 3C. To further characterize the specificity
      of this interaction, the tetraloop and two flanking base pairs of the poliovirus
      RNA were randomized, and viable viral clones were obtained using in vivo SELEX.
      Among many different mutants with the canonical YNMG sequences to be described
      elsewhere, a large-plaque-forming clone contained a deviating uGCUAg sequence.
      The NMR structure of a small hairpin capped with uGCUAg that we present here
      shows that the GCUA tetraloop adopts a novel fold, which is highly similar to
      that of the YNMG tetraloop with common stacking properties and hydrogen-bond
      interactions including an unusual syn conformation of the adenosine.
      Thermodynamic studies show moderate stabilities of hairpins with canonical YNMG
      and the novel GCUA loops, which, together with the similarity of spatial
      structures, illustrates that the tetraloop structure itself is crucial for the
      RNA-protein interaction required for the viral replication. A re-evaluation of
      the ribosomal secondary structure database reveals a hairpin containing a GCUA
      loop, which covaries with YNMG and is involved in a tertiary interaction, and in
      the 50S ribosomal subunit from Haloarcula marismortui the structurally comparable
      apex of stem-loop 35a is a recognition site for protein L2. These observations
      show a more general occurrence and importance of the so-far unrecognized GYYA
      hairpin loops.

PMID- 16894218
TI  - Low abundance of telomerase in yeast: implications for telomerase
      haploinsufficiency.
AB  - Telomerase is an RNA-dependent reverse transcriptase that maintains telomeric DNA
      at a species-specific equilibrium length. To determine an upper limit for the
      number of telomerase molecules in a Saccharomyces cerevisiae cell, we have
      established real-time RT-PCR assays to quantify the noncoding telomerase RNA,
      TLC1. We find that the number of TLC1 molecules in a haploid yeast cell is
      approximately 29, less than the number of chromosome ends (64) in late S-phase.
      Wild-type diploid cells contain approximately 37 telomerase RNAs, while diploids
      heterozygous for a null tlc1 allele have half the wild-type amount, approximately
      19 TLC1 molecules. For comparison, there are approximately 480 molecules of the
      U2 snRNA per haploid cell. We show that a biological consequence of this low
      level of telomerase is haploinsufficiency: A TLC1/tlc1Delta heterozygote
      maintains shorter telomeres. A dominant-negative telomerase RNA, with a deletion
      of the template for telomeric DNA synthesis, further demonstrates that yeast
      telomere length is sensitive to telomerase dosage. Sixfold overexpression of
      tlc1Deltatemplate establishes a new telomere length set point, approximately 160
      bp shorter than wild type. Removing telomerase protein-interaction sites from the
      tlc1Deltatemplate RNA mitigates the dominant-negative effect, suggesting that the
      tlc1Deltatemplate RNA competes with wild-type TLC1 for a limited supply of
      telomerase proteins or for telomeres. Because yeast telomerase is tethered at
      chromosome ends, the finding that it may be outnumbered by its telomeric DNA
      substrates provides a new perspective for interpreting the results of telomere
      maintenance studies.

PMID- 16894222
TI  - On being dependent on home mechanical ventilation: depictions of patients'
      experiences over time.
AB  - In this study, the authors describe the meanings of experiences of being
      dependent on a ventilator (HMV) and living at home as narrated by 13 people who
      had been using a ventilator via a mask or tracheostomy for half a year. The
      analyses revealed various movements across time toward the goal of using the
      ventilator successfully, and some narratives depicted suffering caused by care.
      The analyses also yielded different representations of embodiment. These findings
      were abstracted into two contrasting meanings of the experience of using HMV over
      time: a closing in or an opening up of the lived body, oneself, to other people
      and to the world. The authors illustrate this interpretation with two images.
      Ignorance and negative attitudes on the part of professionals working and/or
      managing care in the patients' homes are interpreted as causing suffering and
      intensifying a closed-in mode of being.

PMID- 16894219
TI  - Fluorescence and solution NMR study of the active site of a 160-kDa group II
      intron ribozyme.
AB  - We have reconstructed the group II intron from Pylaiella littoralis (PL) into a
      hydrolytic ribozyme, comprising domains 1-3 (D123) connected in cis plus domain 5
      (D5) supplied in trans that efficiently cleaves spliced exon substrates. Using a
      novel gel-based fluorescence assay and nuclear magnetic resonance (NMR)
      spectroscopy, we monitored the direct binding of D5 to D123, characterized the
      kinetics of the spliced exon hydrolysis reaction (which is mechanistically
      analogous to the reverse of the second catalytic step of splicing), and
      identified the binding surface of D123 on D5. This PL ribozyme acts as an RNA
      endonuclease even at low monovalent (100 mM KCl) and divalent ion concentrations
      (1-10 mM MgCl(2)). This is in contrast to other group II intron ribozyme systems
      that require high levels of salt, making NMR analysis problematic. D5 binds
      tightly to D123 with a K(d) of 650 +/- 250 nM, a K(m) of approximately 300 nM,
      and a K(cat) of 0.02 min(-1) under single turnover conditions. Within the
      approximately 160-kDa D123-D5 binary complex, site-specific binding to D123 leads
      to dramatic chemical shift perturbation of residues localized to the tetraloop
      and internal bulge within D5, suggesting a structural switch model for D5
      assisted splicing. This minimal ribozyme thus recapitulates the essential
      features of the reverse of the second catalytic step and represents a well
      behaved system for ongoing high-resolution structural work to complement folding
      and catalytic functional studies.

PMID- 16894223
TI  - Social support processes and the adaptation of individuals with chronic
      disabilities.
AB  - In a qualitative study examining turning points in life, 15 adults with chronic
      disabilities (cerebral palsy, spina bifida, or attention deficit disorder)
      provided information about the nature and meaning of their social support
      experiences. The study revealed three types of psychological support linked to
      self-perceptions and enabling beliefs: (a) emotional support (valuing and
      acceptance leading to perceptions of "being believed in" and a sense of self
      esteem), (b) instrumental support (guidance and provision of strategies leading
      to self-efficacy), and (c) cognitive support (affirmation, confirmation, and new
      perspectives leading to coherence in self-concept and worldview). The findings
      have important implications for service delivery with respect to understanding
      client needs for different kinds of support, especially at periods of transition,
      and for providing optimal experiences and creating supportive environments. In
      particular, the role of cognitive support deserves more attention in
      understanding the adaptation of individuals with chronic disabilities.

PMID- 16894224
TI  - Why lower income mothers do not engage with the formal mental health care system:
      perceived barriers to care.
AB  - Lower income mothers who bring their children for mental health services also
      have high rates of depression and anxiety, yet few seek help. Maternal and child
      mental health are intimately intertwined; thus, the distress of both is likely to
      continue if the mother's needs are unaddressed. Because mothers overcome numerous
      instrumental challenges to help their children, the authors identify potential
      perceptual barriers to mothers' help seeking. An ethnographic analysis of in
      depth qualitative interviews with 127 distressed mothers suggests several
      critical perceptual factors. For example, mothers attributed their distress to
      external causes (e.g., poverty, negative life stressors), which they believed
      individually focused mental health services could not affect. Interviewees also
      anticipated negative ramifications for seeking care, including being labeled
      unfit mothers, and thus potentially losing custody of their children. The authors
      discuss the implications of these and other key themes for engaging lower income
      mothers and their children.

PMID- 16894225
TI  - "Notice how you feel": an alternative to detached concern among hospice
      volunteers.
AB  - Medical schools teach physicians to practice "detached concern," a simultaneous
      emotional distance from and sensitivity toward their patients. Medical students
      learn detachment to protect themselves from emotion-laden experiences, including
      death and dying, by employing mechanisms of defense and adjustment, such as
      suppression and repression of emotions. In this study, the author inquires
      whether hospice volunteers are trained for and practice detached concern and
      finds that hospice volunteers are trained for concern. They are concerned for the
      well-being of patients and their families. The author argues that concern is a
      social product that can be trained; hospice volunteers are not trained to
      suppress and repress their emotions, and the hospice as an institution produces
      and transmits cultural norms, values, and practices surrounding death and dying,
      thus maintaining a pool of concerned volunteers.

PMID- 16894220
TI  - Hybrid E. coli--Mitochondrial ribonuclease P RNAs are catalytically active.
AB  - RNase P is a ribonucleoprotein that cleaves tRNA precursors at their 5'-end.
      Mitochondrion-encoded RNA subunits of mitochondrial RNase P (mtP-RNA) have been
      identified in jakobid flagellates such as Reclinomonas americana, in the
      prasinophyte alga Nephroselmis olivacea, and in several ascomycete and zygomycete
      fungi. While the structures of ascomycete mtP-RNAs are highly reduced, those of
      jakobids, prasinophytes, and zygomycetes retain most conserved features of their
      bacterial counterparts. Therefore, these mtP-RNAs might be active in vitro in the
      absence of a protein subunit, as are bacterial P-RNAs. Here we present a
      comparative structural analysis including seven newly characterized jakobid mtP
      RNAs. We investigate ribozyme activities of mtP-RNAs and find that even the most
      bacteria-like molecules of jakobids are inactive in vitro. However, when certain
      domains of jakobid and N. olivacea mtP-RNAs are replaced with those from
      Escherichia coli, these hybrid RNAs show catalytic activity. In vitro mutagenesis
      of these hybrid mtP-RNAs shows that various structural elements play a critical
      role in ribozyme catalysis and provide further support for the presence of these
      elements in mtP-RNAs. These include GNRA tetraloops in helix P14 and P18 of
      Jakoba libera, and a remnant P3 pairing in Seculamonas ecuadoriensis. Finally, we
      will discuss reasons for the failure of mtP-RNAs to show catalytic activity in
      the absence of P-proteins based on our mutagenesis analysis.

PMID- 16894226
TI  - Perceived benefits and difficulties experienced in a mutual support group for
      family carers of people with schizophrenia.
AB  - In this qualitative study, the authors explore from the participants' perspective
      the benefits and difficulties experienced by participants in a mutual support
      group for Chinese family carers of patients with schizophrenia in Hong Kong.
      Thirty family carers and 10 patients who had participated in a 12-session mutual
      support group were interviewed, and the 12 group sessions were audiotaped for
      content analysis. Three main themes emerged from the data: (a) positive personal
      changes attributed to group participation, which included enhanced self-identity
      and acceptance of the caregiving role, increased knowledge of the illness, and
      adoption of new coping skills; (b) positive characteristics of the mutual support
      group, including the explicit group ideology and consensus, perceived social
      climate of the group, and informational support and empowerment; and (c) major
      inhibitors of group development, specifically low or irregular group attendance,
      negative pressure from dominant members, and overexpression of intense and
      negative feelings. These findings contribute to our understanding of the
      therapeutic components and limitations of mutual support groups for family
      carers.

PMID- 16894227
TI  - Managing a medically and socially complex life: women living with lupus.
AB  - Systemic lupus erythematosus is a systemic autoimmune illness that affects women
      more frequently than men and disproportionately affects women of color. Because
      so little is known about living with lupus, the author undertook a qualitative
      study to identify salient aspects of affected women's daily experiences. Seven
      women with lupus participated in three interviews, each separated by 1 month, and
      they also maintained a daily symptom journal. In addition, 23 women recruited
      from the Internet submitted narrative accounts of their experiences of living
      with lupus. Analysis of the findings suggests that living with lupus involves
      managing a medically and socially complex life. The complexity of life with lupus
      is dimensionalized by the overlapping themes, identified as a life of
      uncertainty, a shifting sense of identity, and managing the financial burden of
      illness.

PMID- 16894228
TI  - Reflections on reflecting as a dialogic accomplishment in counseling.
AB  - In this exploratory study, the author examines reflection as a dialogic
      phenomenon constructed in the back-and-forth of counseling dialogue. He
      videotaped and microanalyzed 11 one-hour lifestyle consultations for the
      conversational practices used by counselors and clients in collaboratively
      reflecting on developments in their dialogues. He then invited counselors and
      clients back to comment on their participation in videotaped passages of their
      dialogue selected for microanalysis, thus permitting a juxtaposition of their
      retrospective comments with the analysis. The author considers the results from
      this study with respect to training counselors and for pointing new ways to widen
      the evidence base with respect to interventions in counseling, particularly
      social constructionist approaches.

PMID- 16894230
TI  - Physical exercise as a reinforcer to promote calmness of an ADHD child.
AB  - Age-appropriate reinforcers have been found to be effective in promoting
      attentiveness and calmness with children with attention deficit hyperactivity
      disorder (ADHD). The present study with a 4-year-old ADHD boy found attentive
      calmness was substantially increased from a mean of about 3 seconds per trial to
      the maximum scheduled duration of 60 seconds by using a scheduled period of
      physical activity as the reinforcer for the attentive-calmness. These results
      suggest the possible use of this type of reinforcer as an addition or
      substitution for the usual reinforcers in contingency management with ADHD
      children.

PMID- 16894229
TI  - The relationship between visual analysis and five statistical analyses in a
      simple AB single-case research design.
AB  - This study explored some practical issues for single-case researchers who rely on
      visual analysis of graphed data, but who also may consider supplemental use of
      promising statistical analysis techniques. The study sought to answer three major
      questions: (a) What is a typical range of effect sizes from these analytic
      techniques for data from "effective interventions"? (b) How closely do results
      from these same analytic techniques concur with visual-analysis-based judgments
      of effective interventions? and (c) What role does autocorrelation play in
      interpretation of these analytic results? To answer these questions, five
      analytic techniques were compared with the judgments of 45 doctoral students and
      faculty, who rated intervention effectiveness from visual analysis of 35
      fabricated AB design graphs. Implications for researchers and practitioners using
      single-case designs are discussed.

PMID- 16894232
TI  - An alternative method for quantitative synthesis of single-subject researches:
      percentage of data points exceeding the median.
AB  - The purpose of the present study is twofold: (a) to compare the validation of
      percentage of nonoverlapping data approach and percentage of data points
      exceeding the median of baseline phase (PEM) approach, and (b) to demonstrate
      application of the PEM approach in conducting a quantitative synthesis of single
      subject research investigating the effectiveness of self-control. The results
      show that the PEM had higher Spearman correlation with original authors' judgment
      than PND did. The results of applying the PEM approach to synthesize the effect
      of self-control training on academic and social behavior showed that the
      treatment was highly or at least moderately effective.

PMID- 16894231
TI  - Improving dyadic coping in couples with a stress-oriented approach: a 2-year
      longitudinal study.
AB  - This study sought to assess the effectiveness of a marital distress prevention
      program for couples by examining how marital quality, especially marital
      competencies such as dyadic coping, could be improved by means of a prevention
      program focusing on the enhancement of coping resources (Couples Coping
      Enhancement Training). The study consisted of 59 couples in the intervention
      group and 59 couples in the matched comparison group. The results reveal that it
      is possible to improve marital quality, especially marital competencies, by means
      of one short-term intervention lasting 18 hr. However, the effects decreased
      after 2 years, raising the importance of booster sessions in helping to maintain
      effects over a longer period of time.

PMID- 16894233
TI  - Predicting outcome in parent-child interaction therapy: success and attrition.
AB  - This study explored predictors of treatment response and attrition in Parent
      Child Interaction Therapy (PCIT). Participants were 99 families of 3- to 6-year
      old children with disruptive behavior disorders. Multiple logistic regression was
      used to identify those pretreatment child, family, and accessibility factors that
      were predictive of success or attrition. For all study participants, waitlist
      group assignment and maternal age were the significant predictors of outcome. For
      treatment participants (study participants excluding those who dropped out after
      the initial evaluation but before treatment began), only maternal ratings of
      parenting stress and maternal inappropriate behavior during parent-child
      interactions were significant predictors of treatment outcome. These results
      suggest that for treatment studies of disruptive preschoolers, the benefits of
      using a waitlist control group may be outweighed by the disproportionate number
      of dropouts from this group. Once families begin PCIT, however, parent-related
      variables become salient in predicting treatment outcome.

PMID- 16894234
TI  - Measuring homework compliance in cognitive-behavioral therapy for adolescent
      depression: review, preliminary findings, and implications for theory and
      practice.
AB  - Despite the importance placed on completion of extra-session homework in
      cognitive-behavioral therapy (CBT), a review of the available literature suggests
      there is much about the nature of homework compliance that remains to be
      empirically evaluated. This is especially true among youth receiving CBT. The
      present study begins to address how best to measure homework compliance and
      offers a fine-grained, single-case analysis of homework compliance during acute
      treatment with depressed adolescents. The results demonstrate that 56% of
      homework assignments were completed. Also observed was substantial within-subject
      temporal variability in homework compliance and a tendency for compliance to
      decrease during the course of treatment. These data call into question the
      adequacy of any static aggregate measure of homework compliance and have
      implications for both researchers and clinicians.

PMID- 16894235
TI  - Speed of eating as a determinant of bulimic desire to vomit: a controlled study.
AB  - Studies of self-induced vomiting of retarded persons have found that the rate of
      eating and the amount eaten alter this problem. The present study attempted to
      determine whether this same relation was exhibited by the nonretarded bulimic. A
      nonretarded bulimic woman provided her subjective ratings of her desire to vomit
      after eating her taboo foods at a fast versus slowed versus normal rate using a
      within participant experimental design. The desire to vomit was found to be near
      absent after the slowed eating of the taboo foods but was at a high level that
      endured after the rapid or normal eating. These results suggest a neglected
      determinant of adult bulimia that may be used in clinical treatment, pending
      confirmation by a larger sample with measures of actual vomiting as was
      previously evidenced by the inpatient retarded vomiters.

PMID- 16894236
TI  - Monitoring and decreasing public smoking among youth.
AB  - This study examined the impact of tobacco possession laws on public smoking among
      youth. There were two intervention sites: a fast food restaurant and a shopping
      mall. Two control sites were also monitored for public smoking among youth.
      Preliminary findings suggest that when police issued tickets to minors for
      violating tobacco possession laws, the number of youth smoking in public declined
      in both towns, with a more dramatic decrease occurring at the fast food site. In
      contrast, public smoking among youth in the control sites was not affected. The
      significance of reducing number of youth smoking in public through tobacco
      possession laws is discussed.

PMID- 16894237
TI  - Spanish version of the savings inventory-revised: adaptation, psychometric
      properties, and relationship to personality variables.
AB  - The factor structure, psychometric properties, and relationship with personality
      variables of a Spanish version of the Savings Inventory-Revised (SI-R) are
      investigated in a sample of 381 undergraduate students. A maximum likelihood
      factor analysis suggests a three-factor structure, which is similar but not
      identical to that of the original English version. The three factors mirror the
      three hypothesized domains of compulsive hoarding: acquisition, difficulty
      discarding, and clutter. The Spanish SI-R demonstrates acceptable high internal
      consistency and test-retest reliability, but its divergent validity is weaker
      than expected because of a significant overlap with depressive symptoms.
      Different SI-R factors are associated with different personality traits: Whereas
      the difficulty discarding dimension is predominantly associated with
      susceptibility to punishment, the acquisition dimension is predominantly
      associated with susceptibility to reward. The authors conclude that the Spanish
      SI-R is a promising instrument to measure hoarding symptoms.

PMID- 16894238
TI  - Effects of adding on-the-job feedback to conventional analog staff training in a
      nursing home.
AB  - The aims of this study were to examine effects of on-the-job feedback after
      conventional analog staff training and to corroborate earlier findings of
      competent performance maintained without feedback from others. The study took
      place in a nursing home with four staff participants and a resident with problem
      behaviors. A multiple baseline design with measures of staff and resident
      behavior was used, supplemented with social validity reports. The staff training
      program consisted of conventional group workshops plus individual on-the-job
      feedback. During maintenance, staff members continued recording resident
      behaviors but without further on-the-job feedback. Results show that after
      workshop training, staff performance increased, but only one staff participant
      demonstrated competency. With on-the-job feedback, all staff participants
      achieved and maintained competency. Procedures were effective and acceptable, and
      resident behaviors showed corresponding changes.

PMID- 16894239
TI  - Ezetimibe inhibits the incorporation of dietary oxidized cholesterol into
      lipoproteins.
AB  - Oxidized cholesterol is present in significant quantities in the typical Western
      diet. When ingested, oxidized cholesterol is absorbed by the small intestine and
      incorporated into both chylomicrons and LDL, resulting in LDL that is more
      susceptible to further oxidation. Feeding studies in animal models and
      epidemiological studies in humans have suggested that oxidized cholesterol in the
      diet increases the development of atherosclerosis. In this study, we determined
      the effect of ezetimibe, a drug that inhibits small intestinal absorption of
      cholesterol, on the levels of oxidized cholesterol in the serum after a test meal
      containing oxidized cholesterol. We demonstrate that ezetimibe, 10 mg per day for
      1 month, markedly reduced the levels (50% decrease) of oxidized cholesterol in
      the serum after feeding a test meal containing either alpha-epoxy cholesterol or
      7-keto cholesterol, two of the predominant oxidized cholesterols found in the
      diet. Moreover, the decrease in oxidized cholesterol in the serum was
      attributable to a decrease in the incorporation of dietary oxidized cholesterol
      into both chylomicrons and LDL. Because there was no decrease in postprandial
      triglyceride levels, we conclude that this decrease in oxidized cholesterol
      levels in the serum is attributable to decreased absorption and not to enhanced
      clearance. Whether this decrease in oxidized cholesterol absorption prevents or
      delays the development of atherosclerosis remains to be determined.

PMID- 16894241
TI  - Pluronic L81 enhances triacylglycerol accumulation in the cytosol and inhibits
      chylomicron secretion.
AB  - Pluronic L81 (PL81) inhibits fat absorption, and other Pluronic copolymers help
      overcome drug resistance in cancer cells. To understand how PL81 acts, we
      synthesized a radiolabeled analog, [14C]PL81, and showed that it was structurally
      similar to PL81 based on (1)H NMR as well as mass spectrometric analysis.
      [14C]PL81 inhibited the secretion of chylomicrons (CMs), lipoproteins essential
      for fat absorption, by differentiated Caco-2 cells similar to PL81. Moreover,
      PL81 competed with the cellular uptake of [14C]PL81. Thus, [14C]PL81 and PL81
      behave similarly in these physiologic assays. Uptake of [14C]PL81 by Caco-2 cells
      was concentration-, time-, and temperature-dependent and occurred mainly from the
      apical side. Intracellularly, it was assimilated in the cytosol. Cells excreted
      PL81 toward the apical side via a pathway partially sensitive to verapamil. Small
      amounts were secreted toward the basolateral side unassociated with CM, and this
      secretion was unaffected by the inhibition of CM assembly. Nonetheless, PL81
      significantly inhibited the secretion of triacylglycerols (TGs) and phospholipids
      as part of CM. PL81-treated cells showed decreased activity of microsomal
      triglyceride transfer protein and accumulated more TGs, but not phospholipids, in
      their cytosol. We propose that Pluronic copolymers act by interfering with the
      export of molecules from the cytosol. They inhibit fat absorption by decreasing
      TG transport to the endoplasmic reticulum and increase drug efficacy against
      cancer cells by competing for their excretion.

PMID- 16894243
TI  - Assessment of global risk: a foundation for a new, better definition of
      hypertension.
AB  - The prevalence of individuals with increased blood pressure (BP) is growing. A
      greater understanding of the various pathogenetic mechanisms of hypertension and
      associated BP increases would provide a better strategy for preventing and
      treating this condition. Hypertension is strongly associated with other
      cardiovascular risk factors. Additionally, there is no threshold of BP >115/70 mm
      Hg that identifies cardiovascular risk (i.e., risk is linear and doubles for each
      20/10-mm Hg BP rise). These insights have led a group of hypertension experts to
      propose a new definition of hypertension as "a progressive cardiovascular
      syndrome arising from complex and interrelated etiologies," which features early
      markers that are "often present before blood pressure elevation is sustained."
      Early cardiovascular markers include widened pulse pressure, left ventricular
      hypertrophy, increased arterial stiffness, endothelial dysfunction, and
      microalbuminuria. Importantly, antihypertensive treatment for patients with
      prehypertension (systolic BP of 120-139 mm Hg or diastolic BP of 80-89 mm Hg) has
      recently been shown to prevent the development of frank hypertension. This
      revision of the definition of hypertension and the need to assess BP levels in
      the context of global cardiovascular risk should lead to earlier detection of at
      risk patients.

PMID- 16894240
TI  - The lipogenic enzymes DGAT1, FAS, and LPL in adipose tissue: effects of obesity,
      insulin resistance, and TZD treatment.
AB  - Acyl-coenzyme A:diacylglycerol transferase (DGAT), fatty acid synthetase (FAS),
      and LPL are three enzymes important in adipose tissue triglyceride accumulation.
      To study the relationship of DGAT1, FAS, and LPL with insulin, we examined
      adipose mRNA expression of these genes in subjects with a wide range of insulin
      sensitivity (SI). DGAT1 and FAS (but not LPL) expression were strongly correlated
      with SI. In addition, the expression of DGAT1 and FAS (but not LPL) were higher
      in normal glucose-tolerant subjects compared with subjects with impaired glucose
      tolerance (IGT) (P < 0.005). To study the effects of insulin sensitizers,
      subjects with IGT were treated with pioglitazone or metformin for 10 weeks, and
      lipogenic enzymes were measured in adipose tissue. After pioglitazone treatment,
      DGAT1 expression was increased by 33 +/- 10% (P < 0.05) and FAS expression
      increased by 63 +/- 8% (P < 0.05); however, LPL expression was not altered.
      DGAT1, FAS, and LPL mRNA expression were not significantly changed after
      metformin treatment. The treatment of mice with rosiglitazone also resulted in an
      increase in adipose expression of DGAT1 by 2- to 3-fold, as did the treatment of
      3T3 F442A adipocytes in vitro with thiazolidinediones. These data support a more
      global concept suggesting that adipose lipid storage functions to prevent
      peripheral lipotoxicity.

PMID- 16894244
TI  - Historical perspectives on the management of hypertension.
AB  - As late as the 1950s, elevated blood pressure was considered by many expert
      physicians to be necessary for the adequate perfusion of vital organs. Although
      the morbidity and mortality risks of hypertension were known at that time to
      insurance companies, which often refused life insurance policies to people with
      high blood pressure, there was a lag in the recognition of the dangers of
      hypertension in the medical community. Following the pioneering efforts of
      researchers who began to treat patients with malignant hypertension, the results
      of clinical trials and population studies, and the availability of effective
      antihypertensive agents, hypertension management improved rapidly. This review
      traces the history of hypertension management from the 1940s, when President
      Franklin Delano Roosevelt died of a cerebrovascular accident-a result of
      uncontrolled hypertension-to today, when a large number of patients, even those
      with less severe hypertension, are being treated successfully, with a resulting
      dramatic decrease in hypertension-related vascular disease.

PMID- 16894245
TI  - Management of global risk across the continuum of hypertensive heart disease.
AB  - Identification and management of cardiovascular (CV) risk factors are essential
      to help prevent CV disease and slow its progression. Long-term epidemiologic data
      show that hypertension is associated with a two- to four-fold increase in CV
      morbidity and mortality; moreover, antihypertensive therapy has been proven to
      significantly reduce the risk of CV events. Clinical trial data also suggest that
      different antihypertensive agents generally provide similar reductions in CV
      risks and outcomes. Beta blockers have historically played an integral role in
      hypertension treatment, particularly among patients at high CV risk; however, a
      recent meta-analysis, based primarily on the use of atenolol, found that beta
      blockers may provide less clinical benefit as initial therapy than other classes
      of antihypertensive agents. Beta blockers are heterogeneous, and atenolol data
      may not be representative of other beta blockers. Newer beta blockers, which
      provide both cardioselective beta1-adrenergic receptor blockade and endothelium
      dependent vasodilation, may prove to be more effective in reducing CV morbidity
      and mortality. Intensive strategies to control global CV risk have been shown to
      significantly reduce CV events. The challenge remains to develop effective risk
      assessment tools to identify at-risk patients who often go undetected.

PMID- 16894248
TI  - Cardiovascular medicine and surgery in 2011.

PMID- 16894246
TI  - Nitric oxide mechanisms in the pathogenesis of global risk.
AB  - Identification and management of cardiovascular risk factors, such as
      hypertension, diabetes mellitus, and dyslipidemia, is essential not only for
      prevention of cardiovascular disease, but also for slowing the progression of
      existing cardiovascular disease. A major underlying mechanism that links various
      cardiovascular risk factors and manifestations of cardiovascular disease is
      endothelial dysfunction, characterized by impaired nitric oxide bioactivity.
      Oxidative stress is an important cause of impaired nitric oxide bioactivity, and
      a major pathogenic mechanism of atherosclerosis. Several pharmacologic therapies,
      including angiotensin-converting enzyme inhibitors, calcium channel blockers,
      statins, and the vasodilating beta blocker nebivolol, have been shown to enhance
      nitric oxide bioactivity and improve endothelial function. This effect may help
      explain the cardioprotective benefits of these agents and may stimulate further
      use of nitric oxide modulation for the treatment of cardiovascular risk factors
      and manifestations of cardiovascular disease.

PMID- 16894250
TI  - Is the future here and now and passed you by?

PMID- 16894249
TI  - The players and the stage are changing: the current cardiovascular surgical
      crisis--is there a future?

PMID- 16894251
TI  - Future directions in cardiac surgery.
AB  - The future of cardiac surgery is interesting, challenging, and changing. In
      coronary artery disease, operations are becoming more difficult due to previous
      stent placement and population aging, but there is a sense that volume is
      increasing, especially in centers that perform operations for diffuse disease and
      those that can perform truly minimally invasive procedures with robotic takedown
      of mammary arteries and perform anastomoses thoracoscopically. In valve disease,
      there will be increasing numbers of elderly patients requiring surgery,
      especially for aortic valve disease; a combination of minimally invasive surgery,
      hybrid procedures, and perhaps percutaneous valve placement in the truly high
      risk will be required. Mitral valve repair will become increasingly used as well
      as some percutaneous valve devices. In 5 years, most thoracic aneurysms will be
      treated by endovascular stenting and adults with congenital disease will be a
      small but growing population of patients.

PMID- 16894252
TI  - Cardiac surgery: the next 5 years.

PMID- 16894253
TI  - Projecting developments in robotic cardiac surgery: the next 5 years.

PMID- 16894255
TI  - Interventional cardiology in 5 years.

PMID- 16894254
TI  - Percutaneous valve interventions: where we are and where we are headed.
AB  - Boundaries between the specialties of cardiology and cardiovascular surgery are
      becoming less distinct, as cardiologists and cardiac surgeons alike strive to
      decrease invasiveness of procedures and improve patient results. For surgeons,
      new tools and techniques have allowed innovative, minimally invasive techniques
      to be performed successfully with smaller incisions and faster recovery. With the
      introduction of novel catheter technology, aortic valve prostheses can be placed
      percutaneously or, more recently, transapically without cardiopulmonary bypass.
      Furthermore, the field of percutaneous mitral valve repair is rapidly expanding
      with multiple novel off-pump percutaneous devices designed to reduce or eliminate
      mitral regurgitation, including devices that perform edge-to-edge leaflet repair
      and percutaneous mitral annuloplasty. The explosive growth of new ideas and new
      procedures to decrease invasiveness of valve procedures will continue to evolve
      over the next 5 years, and surgeons must remain nimble to become part of this
      process.

PMID- 16894256
TI  - The 5-year projection on the future of interventional cardiology.
AB  - Interventional cardiology has revolutionized modern cardiovascular care not only
      with the introduction of new approaches to the treatment of coronary artery
      disease, but also with the development of new invasive approaches to
      electrophysiologic procedures and the treatment of noncoronary vascular beds.
      This revolution continues to gather speed. Creative solutions continue to be
      proposed, evaluated, and then brought to the patient care arena. Issues remain,
      but these identify opportunities for continuing improvement.

PMID- 16894258
TI  - Percutaneous pulmonary valve implantation: a 5-year projection.

PMID- 16894257
TI  - Interventional cardiology: evolution and future.

PMID- 16894260
TI  - The future of cell therapy for myocardial regeneration.
AB  - There are a number of promising cell therapy products under development for the
      treatment of heart failure, whether due to myocardial infarction or
      cardiomyopathy. Looking forward beyond current products in development, there are
      a multitude of possibilities that hold significant promise; however, cell-based
      therapies present challenges that are unique to this platform. Results from
      transplant studies can often be misleading and need to be interpreted in the
      context of fundamental biologic properties of cells and development. Provided
      here is a summary of the current and future developments in the field of cell
      therapy for cardiac regeneration along with some critical insights to interpret
      the multitude of studies recently undertaken. Summarized are both clinical and
      preclinical studies that should serve as a useful entree into this exciting new
      field of therapeutic development.

PMID- 16894259
TI  - The management of heart failure 5 years hence.

PMID- 16894261
TI  - Cell therapy: a 21st-century hope for treating cardiovascular disease--what do
      the next 5 years hold?

PMID- 16894262
TI  - Personalized genomic medicine: a future prerequisite for the prevention of
      coronary artery disease.
AB  - Within the next 10-15 years, medicine will be personalized in large part on the
      basis of the individual's genomic variants. Coronary artery disease remains the
      number one cause of morbidity and mortality in the Western world and is predicted
      to become the number one cause worldwide by 2010. It has been stated that
      treating the risk factors of coronary artery disease has made it a preventable
      disease that should be eliminated in the 21st century. It is postulated that
      about 50% of susceptibility to coronary artery disease is genetic, involving
      known and occult risk factors. Thus, comprehensive prevention will require
      identification of genetic susceptibility. The recent technology of a chip with
      500,000 DNA markers makes genome-wide scanning to identify the genes contributing
      to coronary artery disease possible. Multislice CT will provide the high
      throughput coronary arteriograms required for this research and for prevention in
      asymptomatic individuals with a family history of heart disease.

PMID- 16894263
TI  - The future of cardiovascular biomarkers.

PMID- 16894265
TI  - Cardiovascular imaging: projections for the next 5 years.

PMID- 16894264
TI  - Echocardiography: prospects for the next 5 years.

PMID- 16894266
TI  - Developments in electrocardiography and related fields: a 5-year prognosis.

PMID- 16894267
TI  - The utility of heart sounds and systolic intervals across the care continuum.
AB  - Acoustic cardiography is an exciting, new, easy-to-use, modernized technology
      that incorporates already proven techniques of phonocardiography. Application of
      acoustic cardiography to clinical practice can improve diagnosis and management
      of heart failure patients. Its clinical use should help address some of the need
      for robust, inexpensive, and widely accessible technology for proactive heart
      failure diagnosis and management. Acoustic cardiographically recorded
      measurements have been correlated with both cardiac catheterization and
      echocardiographically determined hemodynamic parameters. Heart sounds captured by
      acoustic cardiograms have proven to assist clinicians in assessing dyspneic
      patients in the emergency department by utilizing the strong specificity of an S3
      for detecting acute decompensated heart failure. Acoustic cardiography offers a
      cost-efficient, easy-to-use method to optimize the devices used in cardiac
      resyncronization therapy. The rapidly and easily obtainable information gathered
      by acoustic cardiography should foster its more widespread use in diagnosis and
      treatment of heart failure, including cardiac resyncronization therapy device
      optimization.

PMID- 16894268
TI  - Hemodynamic correlates of the third heart sound and systolic time intervals.
AB  - Bedside diagnostic tools remain important in the care of patients with heart
      failure. Over the past two centuries, cardiac auscultation and phonocardiography
      have been essential in understanding cardiac pathophysiology and caring for
      patients with heart disease. Diastolic heart sounds (S3 and S4) and systolic time
      intervals have been particularly useful in this regard. Unfortunately,
      auscultation skills have declined considerably, and systolic time intervals have
      traditionally required carotid pulse tracings. Newer technology allows the
      automated detection of heart sounds and measurement of systolic time intervals in
      a simple, inexpensive, noninvasive system. Using the newer system, the authors
      present data on the hemodynamic correlates of the S3 and abnormal systolic time
      intervals. These data serve as the foundation for using the system to better
      understand the test characteristics and pathophysiology of the S3 and systolic
      time intervals, and help to define their use in improving the bedside diagnosis
      and management of patients with heart failure.

PMID- 16894269
TI  - Systolic dysfunction: correlation of acoustic cardiography with Doppler
      echocardiography.
AB  - For detection of left ventricular (LV) systolic dysfunction in the outpatient
      setting, simultaneous electrocardiographic and heart sound data have been shown
      to be helpful. In 161 patients with suspected or known cardiac disease,
      echocardiography and acoustic cardiography were performed. Acoustic cardiographic
      parameters correlated to echocardiography included: presence or absence of S3,
      electromechanical activation time (EMAT), LV systolic time (LVST), and EMAT/LVST.
      LV ejection fraction was >or=50% in 82 patients (S3 present in 9.8%) and <50% in
      79 patients (S3 present in 30.4%; the <50% group also had a greater EMAT,
      EMAT/LVST, and lower mean LVST [p<0.05]). Patients with an S3 had a lower
      ejection fraction, larger mean left atrial and LV dimensions, and an increased
      proportion of diastolic dysfunction. Acoustic cardiography allows reliable
      detection of the S3, which correlates with echocardiographic evidence of impaired
      LV function, and the EMAT/LVST ratio reflects reduced ejection fraction,
      providing an affordable, accessible means to assess LV dysfunction in the
      outpatient setting.

PMID- 16894270
TI  - Acoustic cardiographic parameters and their relationship to invasive hemodynamic
      measurements in patients with left ventricular systolic dysfunction.
AB  - Data obtained at cardiac catheterization were used to evaluate the utility of
      acoustic cardiographic data in assessing the hemodynamic abnormalities associated
      with left ventricular systolic dysfunction (LVSD). Thirty-seven patients (mean
      age, 62.6 years) underwent catheterization, and hemodynamic data were recorded.
      Acoustic cardiographic recordings were obtained using a system that records and
      algorithmically interprets diastolic heart sounds and parameters analogous to
      traditional systolic time intervals. Seventeen patients had LVSD (defined as
      ejection fraction <50%). The 17 patients with LVSD composed the cohort for
      analysis. There were strong associations between acoustic cardiographic
      parameters and left ventricular end-diastolic pressure, ejection fraction, and
      maximum contractility. Heart rate tended to influence the strength of these
      correlations. The authors conclude that acoustic cardiographic data can be used
      in the evaluation of patients with known or suspected LVSD, and specifically in
      the selection of patients for cardiac resynchronization therapy and the
      optimization of the settings of implanted resynchronization devices.

PMID- 16894271
TI  - Optimization of cardiac resynchronization devices using acoustic cardiography: a
      comparison to echocardiography.
AB  - Optimization of pacemaker settings for cardiac resynchronization therapy (CRT)
      remains challenging and problematic. Several noninvasive methods are offered to
      customize the programmed parameters for individual patients, but so far only
      echocardiographic imaging has established itself as an accepted method. The
      authors examined the value of acoustic cardiography as a fast and more cost
      efficient alternative to established echocardiographic imaging techniques for the
      optimization of CRT devices. The atrioventricular delay in 22 subjects with
      implanted CRT devices was independently optimized using echocardiography (Doppler
      transmitral flow) as well as acoustic cardiography, and the recommended settings
      from each method were later compared. Doppler echocardiography and acoustic
      cardiography recommendations matched within a mean value +/- SD of 17+/-16
      milliseconds and gave a correlation coefficient of r=0.90 (p<0.001). In 17 of the
      22 cases (77.3%), the difference between echocardiographic and acoustic
      cardiogram CRT optimization results was <or=20 milliseconds. Furthermore, the
      echocardiographic transmitral flow pattern was not significantly different for
      the setting independently chosen by the echocardiographic expert and the acoustic
      cardiographer for the cases with a difference of >20 milliseconds (22.7%). In
      addition, it took less time for the acoustic cardiogram to collect sufficient
      information to make a recommendation, and it was found that the acoustic
      cardiogram data trend is easier to interpret.

PMID- 16894273
TI  - Optimization of atrioventricular and interventricular delay with acoustic
      cardiography in biventricular pacing.

PMID- 16894272
TI  - Clinical and economic benefits of using AUDICOR S3 detection for diagnosis and
      treatment of acute decompensated heart failure.
AB  - Because many of the signs and symptoms of acute decompensated heart failure
      (ADHF) are nonspecific (e.g., dyspnea), accurate diagnosis can be challenging.
      Highly specific indicators of ADHF can assist in early and accurate diagnosis,
      therefore providing a potential for better outcomes and cost efficiency.
      Demographic, clinical, laboratory, and electronically detected S3 data (Inovise
      Medical, Inc., Portland, OR) were collected in 340 emergency department patients
      with suspected ADHF. After hospital discharge, two blinded cardiologists
      determined whether ADHF was present. Total hospital charges were also recorded.
      The overall ED misdiagnosis rate was 14.0%, of which over 90% were a failure to
      recognize ADHF when it was present. The S3 was highly specific (94%) for ADHF and
      was valuable in combination with BNP values to improve the diagnostic accuracy in
      undifferentiated emergency department dyspenic patients. Misdiagnosed ADHF
      patients accrued over $2500 more in hospital charges than patients correctly
      diagnosed with ADHF, a 32% increase.

PMID- 16894274
TI  - Acoustic cardiography in the differential diagnosis of dyspnea.

PMID- 16894275
TI  - The cardio-renal-anemia syndrome in elderly subjects with heart failure and a
      normal ejection fraction: a comparison with heart failure and low ejection
      fraction.
AB  - The prevalence and severity of anemia and renal dysfunction in heart failure
      patients with a normal ejection fraction (HFNEF) is uncharacterized. Two hundred
      eighty-five consecutive patients admitted to a community hospital with heart
      failure were stratified by the presence or absence of anemia and a normal or
      reduced ejection fraction. Comparisons of clinical variables were performed. In
      this sample, 62% of subjects were anemic, with no difference between those with a
      normal and a reduced ejection fraction (63% vs. 61%). Anemic HFNEF subjects had a
      lower glomerular filtration rate (37 +/- 21 mL/min vs. 52 +/- 35 mL/min; p <
      0.05) and more severe self-reported symptom scores than nonanemic HFNEF subjects.
      Multivariate analysis confirmed the association of renal dysfunction and anemia.
      The authors conclude that the degree and magnitude of anemia in elderly
      inpatients with heart failure does not differ by ejection fraction. Worse
      symptoms and more severe renal dysfunction were seen in HFNEF subjects with
      anemia than in HFNEF subjects without anemia.

PMID- 16894276
TI  - Effect of cardiac resynchronization therapy on diastolic dysfunction as assessed
      by transthoracic two-dimensional Doppler echocardiography.
AB  - Cardiac resynchronization therapy (CRT) in patients with left ventricular
      systolic dysfunction and electrical dyssynchrony has been shown to improve
      morbidity and mortality. Improvement in diastolic dysfunction may contribute to
      these results. In this retrospective study, the authors assessed the effect of
      CRT on the E/A ratio and mitral valve deceleration time, which are commonly
      utilized parameters of left ventricular diastolic function. In 13 patients (aged
      62 +/- 11.3 years), the E/A ratio increased from 1.17 +/- 0.58 to 1.49 +/- 0.66
      (p = nonsignificant) and the mitral valve deceleration time increased from
      178.48+/-57.71 milliseconds to 227.70 +/- 76.18 milliseconds (p = 0.054) post
      CRT. In patients without mitral regurgitation, there was a significant increase
      in E/A ratio, from 1.22 +/- 0.4 to 1.86 +/- 0.47 (p = 0.025), but no significant
      change in the mitral valve deceleration time post-CRT was observed. These data
      suggest improvement in diastolic dysfunction as assessed by routine two
      dimensional echocardiography in patients who receive CRT devices.

PMID- 16894277
TI  - A new angle on the Angle of Louis.
AB  - Previous literature has stated that the center of the right atrium lies
      approximately 5 cm below the sternal angle regardless of body position. Our
      objective was to measure the distance from the Angle of Louis to various
      locations in the right atrium and determine whether these distances vary with
      patients' body habitus. The authors conducted a cross-sectional study with 52
      consecutive patients who underwent computed tomography. The Angle of Louis was
      measured to various right atrial anatomic locations and was correlated with
      patients' body habitus characteristics. There was a positive correlation between
      patients' weight or body mass index and the distance of the Angle of Louis to
      right atrial locations. Therefore, using the traditional 5 cm in an obese patient
      can and usually will result in an underestimation of right atrial pressure. The
      authors suggest that in patients with body mass index > 35 kg/m2 (body surface
      area > 2.5 m2), a jugular venous column height at the clavicle is likely to
      indicate significantly elevated jugular venous pressure and should be considered
      abnormal. Therefore, further clinical assessment and subsequent therapeutic
      decisions of these morbidly obese patients with abnormal jugular venous pressures
      should be made accordingly.

PMID- 16894278
TI  - Racial differences in potassium response to spironolactone in heart failure.
AB  - Evidence of racial differences in aldosterone concentrations and K+ disposition
      suggests that response to aldosterone antagonism might vary by race. The authors
      sought to determine whether K+ response to spironolactone differs between African
      Americans and Caucasians with heart failure. Heart failure patients of African
      American (n = 34) or Caucasian (n = 17) race were started on spironolactone 12.5
      mg/d, with up-titration as tolerated. Laboratory values and drug therapy were
      similar between racial groups at baseline. Spironolactone was titrated to a
      median dose of 25 mg/d in both groups. Neither concomitant medications nor serum
      creatinine changed significantly in either group during spironolactone dose
      titration. Median serum K+ concentrations increased by 0.5 mEq/L (range, -0.7 to
      1.6 mEq/L) in Caucasians, but only 0.1 mEq/L (range, -0.8 to 0.9 mEq/L) in
      African Americans; p < 0.01. These data suggest that African Americans with heart
      failure may be less responsive to the renal effects of spironolactone.

PMID- 16894279
TI  - Beta-blocker therapy for heart failure: should the therapeutic target be dose or
      heart rate reduction?
AB  - Therapeutic target with beta blockers in heart failure, i.e., target heart rate
      reduction or beta-blocker dose, is controversial. To resolve this controversy,
      the authors studied 152 heart failure patients on beta blockers who were divided
      into four groups based on median peak exercise heart rate reduction as compared
      with predicted and prescription of at least 50% recommended beta-blocker dose.
      Event-free survival (vs. death or assist device placement or urgent
      transplantation) was compared. Baseline and peak exercise heart rates were 74 +/-
      14 and 116 +/- 21 bpm, respectively. Median heart rate reduction at peak exercise
      was 35%. When median or higher peak heart rate reduction was achieved, there were
      no significant survival differences noted between patients on different beta
      blocker doses. With below-median peak heart rate reduction, there was a strong
      trend toward better event-free survival with higher beta-blocker doses. In
      conclusion, the results suggest that higher heart rate reduction is associated
      with better outcomes for heart failure patients overall and, for patients with
      persistently elevated heart rates, higher beta-blocker doses provided additional
      benefit.

PMID- 16894280
TI  - What is the optimal angiotensin-converting enzyme inhibitor dose in heart
      failure?
AB  - Doses of angiotensin-converting enzyme (ACE) inhibitors used in the landmark
      heart failure trials that demonstrated survival benefit are rarely reached in
      routine practice. The authors review the current literature regarding optimal
      dosing of ACE inhibitors in heart failure with specific focus on neurohormonal,
      functional capacity, and clinical outcomes. Neurohormonal studies have shown that
      lower ACE inhibitor dosing may provide inadequate suppression of the renin
      angiotensin-aldosterone system. Higher doses of ACE inhibitors have resulted in
      greater increments in exercise and functional capacity. Clinically, patients on
      high-dose ACE inhibitor therapy had significant reductions in all-cause mortality
      or hospitalization, cardiovascular hospitalizations, and heart failure-specific
      hospitalizations. There is, however, conflicting evidence, and so continued
      uncertainty exists regarding optimal dosing. Despite underutilization of ACE
      inhibitors, there is insufficient evidence to support lower doses. Likewise,
      limited data exist for doses higher than those used in the landmark trials.
      Clinicians should therefore attempt to reach target doses in heart failure
      whenever possible.

PMID- 16894281
TI  - Cardiac resynchronization therapy: a practical guide for patient management after
      device implantation, part II.
AB  - This is the second of a two-part series on strategies for optimizing the delivery
      of cardiac resynchronization therapy (CRT). A previous article presented
      strategies to optimize CRT device functioning. This article focuses on patient
      related aspects. The 2005 American College of Cardiology/American Heart
      Association (ACC/AHA) Guidelines for Managing Adults with Chronic Heart Failure
      now designate CRT as a class IA recommendation for stage C patients (QRS
      duration, > or = 120 milliseconds; left ventricular ejection fraction, < or =
      35%) who remain symptomatic despite optimal medical therapy. While the evidence
      from prospective randomized controlled trials demonstrates consistent and
      concordant support for CRT in patients with symptomatic heart failure and
      ventricular dyssynchrony, a substantial minority of patients do not experience
      clinical improvement from CRT. In addition to device optimization, optimizing
      individual patient responses is essential. This article discusses measures for
      enhancing the patient's response to a CRT device.

PMID- 16894282
TI  - Angiotensin-converting enzyme inhibition-emerging pulmonary issues relating to
      cough.
AB  - Angiotensin-converting enzyme (ACE) inhibitors are viewed by many as important
      treatment options for both the management of hypertension and the provision of
      end-organ protection. ACE inhibitors have not been looked on as having any
      clearly recognizable direct pulmonary benefits; rather, their pulmonary effects
      have been felt to be a nuisance by virtue of their association with cough. ACE
      inhibitor-related cough is well characterized. What is less well appreciated is
      the relationship between sleep apnea, pneumonia, and ACE inhibitor-related cough.
      These new pulmonary observations in patients afflicted with an ACE inhibitor
      related cough should revive interest in this bothersome side effect.

PMID- 16894283
TI  - A transfusion-related acute myocardial injury.
AB  - It is not uncommon for patients to have adverse reactions during or after blood
      transfusions, as they occur in 1%-6% of all blood transfusions. Although many of
      the reactions are clinically insignificant, a small subset of adverse reactions
      can lead to serious illness and even death. The authors describe a healthy young
      man who exhibited an acute pulmonary injury reaction to a blood product
      transfusion. However, he also suffered significant myocardial insult, as
      documented by decreased left ventricular ejection fraction and a significant rise
      in cardiac biomarkers. Based on current understanding of the pathophysiologic
      mechanisms in transfusion-related acute lung injury, the authors hypothesized
      that coronary endothelial injury may have caused microvascular ischemia or have
      induced acute myocarditis. Empiric treatment with steroids and a beta blocker
      resulted in improved left ventricular function in our patient.

PMID- 16894284
TI  - History of heart failure.

PMID- 16894286
TI  - Early treatment intensification for aggressive non-Hodgkin's lymphoma.

PMID- 16894287
TI  - The emerging concept of antigen-driven lymphomas: epidemiology and treatment
      implications.
AB  - PURPOSE OF REVIEW: Dramatic increases in the incidence of lymphomas worldwide
      have stimulated considerable efforts to identify factors that contribute to the
      etiology of this heterogeneous group of malignancies. The treatment and,
      ultimately, the prevention of lymphoma depend on our understanding of the complex
      interaction of exogenous agents with the molecular milieu which initiates and
      sustains a lymphoid malignancy. This review discusses the current evidence for
      the role of foreign or self antigens in the initiation of lymphomagenesis. RECENT
      FINDINGS: Recent data have demonstrated an increased risk of lymphoma among
      individuals with chronic inflammatory conditions, persistent infections or
      immunodeficient states. Common to these clinical conditions is antigenic
      stimulation leading to an inflammatory cascade of cellular and cytokine reactions
      that may tax the host immune response, provoke tissue injury and eventually
      result in lymphoid neoplasia. SUMMARY: Efforts to detect and suppress chronic,
      antigen-driven inflammation have suggested that neoplastic progression may often
      be interrupted and controlled. Elucidation of the etiologic mechanisms critical
      to the survival of these malignancies would provide promising alternatives for
      the prevention and treatment of some lymphomas.

PMID- 16894288
TI  - Primary cutaneous B-cell lymphoma: classification and treatment.
AB  - PURPOSE OF REVIEW: There has been confusion and debate regarding the definition,
      terminology, and optimal treatment of the different types of primary cutaneous B
      cell lymphomas. This review presents the new World Health Organization-European
      Organization for the Research and Treatment of Cancer classification for
      cutaneous lymphomas; describes clinicopathologic, immunophenotypic, and genetic
      features of the different types of cutaneous B-cell lymphomas in this
      classification; and discusses current views on treatment of these lymphomas.
      RECENT FINDINGS: The three main types of cutaneous B-cell lymphomas in this new
      classification are primary cutaneous marginal zone B-cell lymphoma, primary
      cutaneous follicle center lymphoma, and primary cutaneous large B-cell lymphoma
      (leg type). Primary cutaneous marginal zone B-cell and primary cutaneous follicle
      center lymphoma are indolent types with an excellent prognosis that should be
      treated primarily with nonaggressive therapies. Primary cutaneous large B-cell
      lymphoma (leg type) is an aggressive lymphoma that should be treated primarily
      with aggressive chemotherapy. SUMMARY: The World Health Organization-European
      Organization for the Research and Treatment of Cancer classification will
      contribute to uniform diagnosis, management, and treatment of patients with
      cutaneous B-cell lymphoma and will prevent patients with indolent types of the
      disease from being treated inappropriately with systemic chemotherapy.

PMID- 16894289
TI  - Treatment of early-stage nonbulky Hodgkin lymphoma.
AB  - PURPOSE OF REVIEW: Excellent results have been achieved in the treatment of early
      stage Hodgkin lymphoma for more than 30 years with radiation therapy alone or the
      combined modalities of radiotherapy and chemotherapy. A major concern has been
      the long-term toxicity of treatment, most of which is attributable to
      radiotherapy. Recent trials that attempt to decrease acute and long-term toxicity
      are reviewed. RECENT FINDINGS: To address the problem of late treatment
      morbidity, randomized trials of combined-modality therapy have been conducted
      demonstrating that the number of chemotherapy cycles and the extent and doses of
      radiotherapy can be reduced. Several studies, including three randomized trials
      of chemotherapy alone vs. combined-modality therapy, suggest that chemotherapy
      alone is a reasonable option for the treatment of nonbulky early-stage Hodgkin
      lymphoma. Positron emission tomography after one or two cycles of chemotherapy
      has been found to be highly predictive of treatment outcome for Hodgkin lymphoma.
      Combination chemotherapy alone including gemcitabine, a highly active drug with a
      favorable toxicity profile, with positron emission tomography early during
      treatment is under evaluation. SUMMARY: Less toxic regimens with the aid of
      positron emission tomography may reduce the short-term and long-term toxicities
      of treatment of early-stage nonbulky Hodgkin lymphoma.

PMID- 16894290
TI  - Advances in the management of HIV-related non-Hodgkin lymphoma.
AB  - PURPOSE OF REVIEW: Human immunodeficiency virus infection is associated with an
      increased risk of non-Hodgkin lymphoma. Even with a decrease in AIDS-defining
      illnesses after the advent of highly active antiretroviral therapy, HIV
      associated non-Hodgkin lymphoma remains an important problem. RECENT FINDINGS:
      Low CD4+ T-lymphocyte count, disease stage, performance status, serum lactate
      dehydrogenase, and number of extranodal sites of disease are all important
      prognostic factors for HIV-non-Hodgkin lymphoma. Recent studies have examined the
      role of infusional chemotherapy, as well as immunotherapy, in the treatment of
      aggressive HIV-non-Hodgkin lymphoma, and autologous stem cell transplantation for
      relapsed or refractory HIV-non-Hodgkin lymphoma. New developments in the
      association of viral infection and pathogenesis of certain subtypes of HIV-non
      Hodgkin lymphoma have also recently been reported. SUMMARY: Outcomes of HIV-non
      Hodgkin lymphoma are improving with the routine use of highly active
      antiretroviral therapy and combination chemotherapy. For aggressive HIV-non
      Hodgkin lymphoma, infusional chemotherapy regimens are well tolerated and lead to
      complete response in about 50-75% of cases and a 2-3 years overall survival of 40
      60%. The potential benefit of adding rituximab to combination chemotherapy may be
      offset by infectious complications in severely immunosuppressed patients. HIV
      associated Burkitt lymphoma should be treated with an intensive regimen rather
      than standard cyclophosphamide, doxorubicin, vincristine, prednisone-like
      chemotherapy. Autologous stem cell transplantation should be considered for
      selected patients with relapsed or refractory HIV-non-Hodgkin lymphoma.

PMID- 16894291
TI  - Pathogenesis of AIDS lymphoma: role of oncogenic viruses and B cell activation
      associated molecular lesions.
AB  - PURPOSE OF REVIEW: We discuss recently published studies that elucidate the
      pathogenesis of AIDS-associated lymphoma. RECENT FINDINGS: Several recent reports
      have provided valuable new information on the role of gamma-herpesviruses in the
      pathogenesis of AIDS-associated lymphoma. In addition to this, significant new
      information has become available on how B cell activation-associated DNA
      modifying events, involving activation-induced cytidine deaminase and DNA
      polymerase-eta, contribute to the molecular lesions that result in AIDS
      associated lymphoma. In particular, new evidence that oncogenic viruses can
      directly induce activation-induced cytidine deaminase expression and oncogene
      mutation in human B cells is of central relevance to better understanding the
      pathogenesis of AIDS-associated lymphoma. SUMMARY: New information provides
      insights into the contributions of immune dysfunction and oncogenic virus
      infection to pathogenesis of AIDS-associated lymphoma, and may lead to new
      potential targets for therapeutic intervention in these cancers.

PMID- 16894292
TI  - Update in HIV lymphoma.
AB  - PURPOSE OF REVIEW: Despite the control of HIV infection in industrialized
      nations, individuals infected with HIV remain at increased risk of malignancies.
      Lymphoma is the most common HIV-associated malignancy in these countries. This
      review summarizes progress from January 2005 to March 2006. RECENT FINDINGS:
      Investigators continue to demonstrate that HIV-associated non-Hodgkin's lymphoma
      remains a significant problem, even in the era of highly active antiretroviral
      therapy. The majority of work has been in diffuse large B-cell lymphoma, with
      infusional therapy remaining promising, and rituximab an area of investigation.
      The latter improves complete response rates, but is associated with an increased
      incidence of infections. Biological insights have been gained into the spectrum
      of HIV-associated non-Hodgkin's lymphoma and Hodgkin's disease, and include
      further work on virological co-infections. SUMMARY: The outcome for individuals
      infected with HIV and developing non-Hodgkin's lymphoma and Hodgkin's disease
      continues to improve as insights into the pathophysiology and treatment advance.

PMID- 16894293
TI  - Signal transduction targets in Kaposi's sarcoma.
AB  - PURPOSE OF REVIEW: AIDS-related Kaposi's sarcoma results from co-infection with
      HIV and Kaposi's sarcoma herpesvirus/human herpesvirus-8, which leads to the
      development of an angiogenic-inflammatory state that is critical in the
      pathogenesis of the condition. Recent discoveries regarding Kaposi's sarcoma
      herpesvirus/human herpesvirus-8 infection and its activation of signal
      transduction have led to a greater understanding into Kaposi's sarcoma
      pathogenesis and have identified potential targets for therapy. RECENT FINDINGS:
      Kaposi's sarcoma is driven by Kaposi's sarcoma herpesvirus/human herpesvirus-8
      specific pathways, which include viral G protein-coupled receptor, viral IL-6,
      and viral chemokine homologues. In addition, cellular growth/angiogenic pathways
      such as vascular endothelial growth factor, insulin growth factor, platelet
      derived growth factor, angiopoietin and matrix metalloproteinases are 'pirated'
      by Kaposi's sarcoma herpesvirus/human herpesvirus-8. Recent findings show
      Kaposi's sarcoma herpesvirus/human herpesvirus-8 specific signaling pathways and
      pirated pathways to be important therapeutic targets. SUMMARY: Numerous advances
      have been made recently that expand the understanding of Kaposi's sarcoma
      pathogenesis. These findings and recent clinical trials of targeted therapy for
      treatment are a prelude to a shift in the paradigm of how AIDS-related Kaposi's
      sarcoma is managed.

PMID- 16894294
TI  - Human papillomavirus-related tumors in HIV.
AB  - PURPOSE OF REVIEW: Human papillomavirus-related anogenital cancers are
      theoretically preventable. Many HIV-infected women do not undergo routine
      cervical cytology screening, however, and there are currently no routine anal
      cytology screening programs. This review focuses on recent developments that may
      impact on the future incidence of these cancers: the effect of highly active
      antiretroviral therapy and the imminent approval of vaccines to prevent initial
      human papillomavirus infection. RECENT FINDINGS: Highly active antiretroviral
      therapy has limited benefit to reduce the incidence of cervical intraepithelial
      neoplasia 3 and no benefit to reduce the incidence of anal intraepithelial
      neoplasia 3. Consistent with these findings, there has been no reduction in the
      incidence of cervical and anal cancer since the introduction of highly active
      antiretroviral therapy. More encouraging is the development of highly effective
      preventive human papillomavirus vaccines that are projected to reduce the
      incidence of cervical cancer by up to 70% among vaccinated women. SUMMARY: HIV
      positive men and women remain at risk for human papillomavirus-associated
      cancers, even in the highly active antiretroviral therapy era. Conversely, the
      incidence of anogenital cancers may decline in the future among HIV-positive
      individuals if they received the human papillomavirus vaccine before they
      acquired HIV infection, and studies should be done to assess the safety and
      efficacy of the vaccines in individuals already infected with HIV.

PMID- 16894295
TI  - The growing problem of non-AIDS-defining malignancies in HIV.
AB  - PURPOSE OF REVIEW: The incidence and spectrum of non-AIDS-defining cancers has
      continued to grow. As HIV-infected individuals live longer due to highly active
      antiretroviral therapy, their risk of dying from one of these cancers is
      increased. The recent literature pertaining to non-AIDS-defining cancers is
      reviewed. RECENT FINDINGS: Recent epidemiological studies have identified higher
      rates of carcinoma of the anus, lung, breast, skin, conjunctiva, liver and
      prostate; hematopoietic malignancies such as Hodgkin's lymphoma, plasma-cell
      neoplasia and leukemia; and other neoplasms like melanoma and leiomyosarcoma in
      HIV-positive patients. The role of HIV-induced immunosuppression in the
      development of these non-AIDS-defining cancers appears less important than
      lifestyle habits like smoking and sun exposure, as well as coinfection with human
      papilloma, hepatitis B, hepatitis C and Epstein-Barr viruses. SUMMARY: It is
      unclear whether the growing number of reports on non-AIDS-defining cancers
      reflects a true increased incidence or merely the product of increased
      surveillance, detection and reporting. Highly active antiretroviral therapy not
      only promotes longevity in the HIV-positive population, but may increase their
      risk of developing cancer like Hodgkin's lymphoma. Assertive prevention
      strategies are needed to adequately deal with non-AIDS-defining cancers in an
      aging and growing HIV-positive population.

PMID- 16894296
TI  - Challenges and opportunities for treatment and research of AIDS-related
      malignancies in Africa.
AB  - PURPOSE OF REVIEW: Following our review of AIDS-associated cancer in developing
      nations in 2004, we sought to update recent publications and review data on the
      challenges and opportunities for the treatment and research of AIDS malignancies
      in Africa. RECENT FINDINGS: It is apparent that the burden of AIDS-related
      malignancies and other virus-associated tumors is significant and increasing in
      Africa. Several recent studies report findings on conjunctival squamous cell
      carcinoma and there is a report that Hodgkin's disease, a non-AIDS-defining
      neoplasm, is increasing in incidence. International collaborative partnerships
      dedicated to AIDS malignancies in developing countries are feasible and
      invaluable for clinical strategies to address this aspect of the pandemic. A
      departure point is the ongoing work of the East Africa - Case Western Reserve
      University Collaboration in AIDS malignancies. SUMMARY: The burden of neoplastic
      complications of HIV infection and endemic virus-associated tumors are assuming
      increasing significance in Africa. There is a need to develop nonmyelotoxic
      therapies and approaches that are hypothesis-driven and pathogenesis-based. The
      scarcity and shortages in this region demand that our scientific and therapeutic
      strategies are both suitable and pragmatic for testing in this setting. It is
      also imperative that African investigators lead us in this important endeavor.

PMID- 16894298
TI  - The management of borderline tumours of the ovary.
AB  - PURPOSE OF REVIEW: The treatment of borderline ovarian tumours has been similar
      to that for their invasive counterparts for a long time. However, in view of the
      good prognosis for borderline ovarian tumours, their occurrence in a younger age
      group and the development of less invasive techniques, the question can be asked
      as to whether a more conservative treatment is warranted. RECENT FINDINGS: Recent
      articles discuss the mode of surgery (laparotomy or laparoscopy), the possibility
      of fertility-sparing surgery, the need for restaging procedures and adjuvant
      therapy. SUMMARY: The ultimate goal in treating patients with borderline ovarian
      cancer is defining those patients with bad prognostic factors and risk for
      recurrence and who consequently require more aggressive therapy. A proper staging
      procedure is crucial to estimate the risk. Translational research might help
      identify borderline tumours with poor prognosis. Fertility-sparing surgery is
      often a good option in young patients with Federation International de
      Gynecologie et Obstetrie (FIGO) stage I disease or in selected cases with
      noninvasive implants, since long-term survival does not seem to be negatively
      influenced by conservative surgery.

PMID- 16894299
TI  - The management of serous papillary uterine cancer.
AB  - PURPOSE OF REVIEW: Uterine papillary serous cancer is an extremely aggressive
      cancer, the optimum management of which is still being determined. It is
      important to understand advances that have been made in 2005 regarding the
      molecular biology, diagnosis, and management of this deadly disease. RECENT
      FINDINGS: The main themes in the literature regarding uterine papillary serous
      cancer are that a potential precursor lesion, serous endometrial intraepithelial
      carcinoma, has been recognized as an early form of the disease. A variety of
      molecular biologically important markers have now been identified, including p53,
      HER2/neu, IL-6, kallikrein 6, and claudin-4, some of which may be susceptible to
      molecularly targeted therapy. Systematic surgical staging is necessary before
      additional therapy is recommended. Stage I uterine papillary serous cancer
      requires aggressive treatment, including surgery, chemotherapy, and radiation
      therapy for successful treatment. The most effective management of advanced stage
      disease remains to be resolved. SUMMARY: Serous endometrial intraepithelial
      carcinoma should be treated as a form of uterine papillary serous cancer.
      Multimodality therapy is required for the successful management of early stage
      uterine papillary serous cancer. Advanced disease is often unresponsive to
      conventional therapy. Molecularly targeted therapies are now being introduced
      into the management of this disease.

PMID- 16894300
TI  - Controversies in the management of germ cell tumours of the ovary.
AB  - PURPOSE OF REVIEW: Ovarian germ cell tumours are rare, but curable at all stages
      of disease. This review gives an outline of the main controversies regarding the
      management of this disease. RECENT FINDINGS: Pelvic malignancies are very rare
      during pregnancy, which should avoid the need for radical surgery or termination
      in these patients. Also during pregnancy, AFP-L2 looks to be a promising tumour
      marker in detecting relapse. Malignant transformation of mature teratomas may be
      predicted by preoperative squamous cell antigen and tumour size. OCT4
      immunohistochemistry has been shown to be a very useful adjunct in the diagnosis
      of dysgerminomas. The traditional method for grading immature teratomas is
      challenged by a new classification. Patients receiving cisplatin-based
      chemotherapy are at a higher risk of developing cardiovascular risk factors.
      There is a hint that high-dose chemotherapy may play a role in relapsed patients.
      SUMMARY: Rarity of the disease means many controversies are difficult to resolve,
      with much reliance on using data from testicular cancer studies. Many clinicians
      still advocate adjuvant chemotherapy for stage I nondysgerminomatous tumours of
      grade 2 and above despite good evidence that surveillance is a safe option, and
      increasing concerns about life-threatening long-term effects of treatment.

PMID- 16894301
TI  - Intraperitoneal chemotherapy for ovarian cancer.
AB  - PURPOSE OF REVIEW: Intraperitoneal chemotherapy for ovarian cancer is based on
      sound pharmacological principles and is technically feasible. There is mounting
      evidence, bolstered by a recent randomized trial, that in certain patients, this
      route of delivery may be superior to traditional intravenous chemotherapy. This
      review explores the background and pharmacokinetic principles of intraperitoneal
      chemotherapy, the recent evidence supporting an intraperitoneal approach, and
      some of the logistical and technical challenges involved. RECENT FINDINGS:
      Intraperitoneal chemotherapy has been evaluated in several settings. Most phase I
      and II data came from second-line treatment of ovarian cancer, and there have
      been a few series, including one recent phase III trial, exploring
      intraperitoneal consolidation. The greatest impact among recent studies will be
      from a large, intergroup phase III trial evaluating intraperitoneal therapy in
      the front-line setting. This study will probably change the dialogue of standard
      treatment for optimally cytoreduced, advanced epithelial ovarian cancer. SUMMARY:
      Based on recent findings, intraperitoneal chemotherapy should be considered for
      the front-line treatment of women with minimal residual advanced ovarian cancer.
      Efforts should continue to facilitate the integration of intraperitoneal
      treatment into mainstream practice, and future trials should be designed to
      address lingering controversy surrounding this route of treatment.

PMID- 16894303
TI  - Bibliography. Current world literature. Lymphoma.

PMID- 16894302
TI  - Chemotherapy for recurrent cervical carcinoma.
AB  - PURPOSE OF REVIEW: If chemotherapy becomes the only treatment option for cervical
      cancer, the prognosis has traditionally been regarded as dismal. Data from
      several recent trials have demonstrated significant improvements in outcome with
      specific cisplatin-containing combinations. The purpose of this review is to
      highlight the evolution of phase III trials leading to current treatment
      standards. RECENT FINDINGS: Given the modest activity of single-agent cisplatin,
      devoid of any meaningful impact on survival, prospective studies focused on other
      drugs that might prove either more effective than, or could be used in
      combination with, cisplatin. Both paclitaxel and topotecan, in combination with
      cisplatin, yielded superior response rates and progression-free survival without
      diminishing patient-reported quality of life; however, only cisplatin plus
      topotecan also improved overall survival. Furthermore, patient-reported quality
      of life is not diminished despite the greater acute toxicity of combination
      regimens. SUMMARY: Despite these chemotherapeutic advances, median survival is
      still less than one year and most patients do not respond to treatment. It is
      important that investigators identify those patients who should participate in
      investigational trials of non-platinum-containing regimens. The next generation
      of clinical trials should explore emerging biological therapies.

PMID- 16894304
TI  - Patient involvement in setting research agendas.
AB  - Patient groups already support funding of trials and patient recruitment for
      colitis research. Patient and public engagement in setting research agendas for
      health research more generally is growing, particularly about the effects of
      treatment. Patient priorities for colitis research span a wide range of
      interests. Opportunities exist to build on strategic alliances between patient
      groups, clinicians and researchers for more open debate about what research
      should be done and how. Traditionally, patients and their families have two roles
      in health research: as research subjects, providing data at the request of
      researchers, and as fundraisers, supporting research and researchers. These roles
      are readily apparent in the area of research into inflammatory bowel disease,
      including colitis, and Crohn's disease, on both sides of the Atlantic. Growing
      evidence, however, suggests that health research agendas do not always reflect
      patients' priorities. Welfare et al. (this issue) add to the evidence by
      eliciting patients' priorities for colitis research. Methods for bridging
      patients' views and research agendas range from social science to deliberative
      public debate. In the first of these, social researchers, such as Welfare et al.
      (this issue), elicit and interpret patients' views and compare these with current
      research agendas. In the second, patients are supported and encouraged to engage
      in debates about research, whereby they bring their own interpretations and
      influence to the health research community. Organized colitis patient groups,
      with their current interests and alliances with research, are well placed to
      build on the work of Welfare et al., in partnership with researchers with the aim
      of planning research that meets the full range of their needs.

PMID- 16894305
TI  - The identification of topics for research that are important to people with
      ulcerative colitis.
AB  - OBJECTIVES: To identify topics for research that are important to people with
      ulcerative colitis, and to provide a framework by which their research priorities
      can be analysed. METHODS: This is a qualitative study using focus groups and
      interviews. Forty people with ulcerative colitis participated. Topics for
      research of importance to participants were identified and analysed using the
      Framework method. RESULTS: Topics were grouped into nine main categories: finding
      the cause of colitis, cure of colitis, prevention of colitis, living with
      colitis, treatment (conventional, complementary and surgical) and its
      complications, control of particular symptoms, information provision,
      communicating with health professionals and methods of service delivery. An
      initial framework to classify the research priorities of people with colitis is
      provided. CONCLUSIONS: This study suggests the potential to utilize patients'
      views to generate research topics that are rarely researched and to involve them
      in setting the research agenda. People with ulcerative colitis are able to
      identify many different areas of research that they feel are important to them.
      This may help to ensure that research is relevant to patients' needs.

PMID- 16894306
TI  - Investigation of serotonin type 4 receptor expression in human and non-human
      primate gastrointestinal samples.
AB  - BACKGROUND: The serotonin type 4 (5-HT4) receptor has been associated with
      functions of the gastrointestinal tract such as modulation of the peristaltic
      reflex, smooth muscle tone, intestinal secretion and visceral sensitivity. The
      activation of peripheral 5-HT4 receptors with agonists such as tegaserod has been
      shown to accelerate gastric emptying and improve symptoms of constipation in
      animals and humans. However, detailed data on the expression profile and on the
      localization of this receptor subtype are lacking so far. OBJECTIVE: To study the
      pattern and expression levels of 5-HT4 receptor messenger RNA expression in the
      gut. METHOD: Normal tissue samples were collected from the whole gastrointestinal
      tract of patients undergoing abdominal surgery and, in addition, of monkeys. We
      performed a comprehensive analysis of 5-HT4 receptor expression by quantitative
      reverse transcription-polymerase chain reaction, using human and non-human
      primate tissues from the oesophagus to the rectum. In addition, the brain and
      heart of non-human primates were analysed. RESULTS: Significantly higher levels
      of 5-HT4 receptor mRNA were measured in the human stomach, duodenum, jejunum,
      ileum and caecum and also in the corresponding non-human primate gut segments,
      ranging from 2- to 12-fold compared with the liver. No differences were found
      between females and males of both human and non-human primates. CONCLUSIONS:
      These results show 5-HT4 receptor mRNA expression throughout the gastrointestinal
      tract in humans and primates, and also support the preclinical and clinical
      findings of 5-HT4 receptors ligands exhibiting multiple effects throughout the
      gastrointestinal tract.

PMID- 16894307
TI  - Digestive calcitonin-secreting tumors of the foregut: comparison with non
      calcitonin-secreting tumors.
AB  - OBJECTIVES: Digestive calcitonin-secreting endocrine tumors are very rare lesions
      of the foregut. This study was undertaken to compare the characteristics and the
      prognosis of these tumors and those of non-calcitonin-secreting endocrine tumors.
      METHODS: All patients with a digestive endocrine tumor of the foregut followed up
      in Reims University Hospital and whose serum calcitonin levels were determined
      between 1988 and 2004 were included. Clinical and tumor characteristics of
      calcitonin-positive and calcitonin-negative patients were compared. RESULTS:
      Thirty-two patients were included. Among the five (15.6%) with high calcitonin
      levels (median: 340 pg/ml, range: 42-7460 pg/ml), only one tumor was functioning
      (diarrhea). Significant differences between patients with positive and negative
      calcitonin levels were, respectively: liver metastases [5 (100%) versus 11
      (40.7%); P=0.04], type according to the World Health Organization 2000
      histological classification [notably 4 (80%) versus 3 (12.5%) poorly
      differentiated endocrine carcinomas; P=0.02] and Ki67 proliferation index
      [median: 25% (range: 20-30%) versus 7% (0-80%); P=0.03]. The only calcitonin
      positive well-differentiated endocrine carcinoma had a high proliferation index
      (30%). Survival also differed significantly (P=0.001), as all calcitonin-positive
      patients died, with a median survival of 22.6 months (range: 1.2-27.2 months),
      versus five (18.5%) calcitonin-negative patients. Median follow-up period for the
      latter was 42.3 months (range: 3.4-208 months). CONCLUSIONS: The secretion of
      calcitonin appears predictive of a poor prognosis. Digestive endocrine calcitonin
      secreting tumors correspond histopathologically to poorly differentiated or well
      differentiated carcinomas with high proliferation indexes.

PMID- 16894308
TI  - Expression of survivin in gastric cancer and its relationship with tumor
      angiogenesis.
AB  - BACKGROUND/AIMS: Survivin, a member of inhibitors of apoptosis, has been found in
      various human cancers. Its expression is associated with tumor progression and
      adverse outcome. Angiogenesis is an essential process for the primary tumor to
      grow and invade the adjacent normal structures. Angiogenic factors such as
      vascular endothelial growth factor induce survivin expression in endothelial
      cells. The current study was designed to investigate the possible role of
      survivin and vascular endothelial growth factor status for angiogenesis in human
      gastric cancer. METHODS: In this study, we conducted an immunohistochemical
      investigation of survivin and vascular endothelial growth factor expression in
      106 tissue samples obtained from gastric cancer patients undergoing surgical
      treatment. To assess tumor angiogenesis, microvessel density was counted by
      staining endothelial cells immunohistochemically using anti-CD34 monoclonal
      antibody. RESULTS: The positive expression of survivin and vascular endothelial
      growth factor in gastric cancer tissues was demonstrated in 50.0 and 69.8% of
      cases, respectively. The expression of survivin did not associate with vascular
      endothelial growth factor expression. Expression of survivin was significantly
      associated with tumor size, depth of invasion, lymph node metastasis, tumor stage
      and poor survival (P=0.011, 0.004, 0.020, 0.002, 0.046, respectively). High
      microvessel density was significantly associated with lymph node metastasis and
      poor survival (P=0.006 and 0.017, respectively). The mean microvessel density
      value of survivin positive tumors was 87.4+/-34.4 and significantly higher than
      that of survivin negative tumors (P=0.016). The mean microvessel density value of
      vascular endothelial growth factor positive tumors was 98.7+/-37.0 and
      significantly higher than that of vascular endothelial growth factor negative
      tumors (P=0.001). A combined analysis of survivin and vascular endothelial growth
      factor status showed that the mean microvessel density value of both positive
      tumors was 103.7+/-33.1 and significantly higher than that of both negative
      tumors (P<0.001). CONCLUSION: These results suggest that survivin may play an
      important role in carcinogenesis by stimulating tumor angiogenesis in human
      gastric cancer.

PMID- 16894309
TI  - Prophylactic aspirin therapy does not increase faecal calprotectin
      concentrations.
AB  - OBJECTIVE: Non-steroidal anti-inflammatory drugs (NSAID) can induce enteropathy.
      Aspirin ingestion is associated with a lower small-intestinal inflammation than
      other NSAID. Faecal calprotectin concentrations have recently been proposed as a
      simple non-invasive test to identify NSAID enteropathy. The aim of our pilot
      study was to evaluate calprotectin concentrations in patients on treatment with
      low-dose aspirin. METHODS: Twenty-two patients on prophylactic treatment with
      aspirin were recruited. Twenty-five healthy volunteers were enrolled as a control
      group. Faecal calprotectin concentrations were determined by enzyme-linked
      immunosorbent assay. Statistical analysis was performed by t-test for unpaired
      data. RESULTS: The mean faecal calprotectin concentration in patients (57.95+/
      44.28 microg/g) did not show significant differences compared with controls
      (45.76+/-26.45 microg/g; P=0.251). CONCLUSIONS: We found that low-dose aspirin
      does not induce an increase in faecal calprotectin increase.

PMID- 16894310
TI  - Prevalence of atypical symptoms and their association with typical symptoms of
      gastroesophageal reflux in Spain.
AB  - BACKGROUND: The association between typical and atypical symptoms of
      gastroesophageal reflux (GER) has received little attention in population-based
      studies. This study therefore sought to examine the prevalence of atypical
      symptoms, and their association with typical GER symptoms in Spain. METHODS: A
      telephone survey using a validated questionnaire was conducted in 2002 on 2500
      subjects aged 40-79 years, randomly selected from the general population of
      Spain. The questionnaire included items on typical GER symptoms (heartburn and
      acid regurgitation) and several atypical symptoms (chest pain, dysphagia,
      belching, dyspepsia, globus, hoarseness, hiccups, chronic cough and asthma). The
      association between typical GER symptoms and each atypical symptom was summarized
      using odds ratios obtained from logistic regression. RESULTS: The response rate
      was 71.2%. A total of 60.8% (95% confidence interval 59.0-62.8%) of subjects
      reported suffering from at least one atypical symptom during the year preceding
      the interview. The prevalence rates varied from 26.7% for hoarseness to 6.6% for
      asthma. The prevalence of atypical symptoms was higher among the 791 subjects
      with typical GER symptoms than among the 1709 subjects reporting no typical GER
      symptoms (79.6 versus 52.2%). It was also higher among those reporting frequent
      typical GER symptoms compared with those reporting occasional symptoms (87.8
      versus 58%). After adjustment for age, sex, coffee, alcohol and tobacco
      consumption, and psychosomatic symptoms, an association (P<0.05) was observed
      between typical symptoms and the respective atypical symptoms, with odds ratios
      ranging from 1.4 for asthma to 4.6 for belching. After additional adjustment for
      the remaining atypical symptoms, chest pain, dysphagia, dyspepsia, belching and
      globus were each independently associated with typical reflux symptoms.
      CONCLUSION: The prevalence of atypical GER symptoms is extremely high. There is
      an association between typical and atypical GER symptoms, particularly chest
      pain, dysphagia, dyspepsia, belching and globus.

PMID- 16894311
TI  - Esophageal capsule endoscopy in patients refusing conventional endoscopy for the
      study of suspected esophageal pathology.
AB  - AIM: Esophageal capsule endoscopy is a well tolerated procedure that does not
      require sedation and has proved its value for the study of the esophagus. The aim
      of our study was to assess the feasibility, accuracy, safety and acceptability of
      esophageal capsule endoscopy for the study of gastroesophageal reflux disease and
      esophageal varices in patients who refused conventional upper gastrointestinal
      endoscopy. PATIENTS AND METHODS: Thirty consecutive examinations performed in 28
      patients (15 men/13 women; mean age: 58.5+/-12.4 years; range: 23-87 years) were
      reviewed. Twenty-five examinations were performed in 23 patients presenting with
      chronic gastroesophageal reflux disease symptoms and the remaining five were
      carried out in patients with cirrhosis for screening of esophageal varices. The
      procedures were done with the new PillCam ESO that harbors two viewing cupules
      and takes a total of 14 frames/s. Technical data (total recording time,
      esophageal transit time and Z-line visualization), clinical findings (Savary
      Miller grade; presence and characteristics of esophageal varices or portal
      hypertension gastropathy), and patient's opinion (quality and comfort
      questionnaire) were analyzed. RESULTS: All the patients ingested and excreted the
      capsule without complications. Two examinations in the gastroesophageal reflux
      disease group were repeated; one was issued as a follow-up and the other because
      no images were recorded in the first capsule endoscopy. From the former, only the
      satisfaction questionnaire was analyzed. Mean total recording time and esophageal
      transit time were 1224 and 243.79 s, respectively (range: 2-1192 s). Complete
      study of the Z-line was possible in 23 examinations (23/29; 79.3%). Esophageal
      erosions were seen in 58.33% (14/24) of the examinations carried out in patients
      with gastroesophageal reflux disease. Nine out of 14 patients (64.29%) presented
      with grade I esophagitis and the other five (35.71%) with grade II esophagitis.
      Among the five patients with cirrhosis, small varices were visualized in one
      (1/5; 20%), while large varices with red spots were evidenced in the remaining
      three (3/5; 60%). All four patients showing esophageal varices were found to have
      portal hypertension gastropathy. In most examinations, patients found the capsule
      easy to swallow (28/30; 93.33%), asymptomatic (29/30; 96.66%), evaluated the
      procedure as comfortable (29/30; 96.66%), and would repeat it if necessary
      (30/30; 100%). CONCLUSIONS: Esophageal capsule endoscopy is an adequate
      alternative diagnostic method for the study of gastroesophageal reflux disease
      and for the screening of esophageal varices in patients refusing to undergo
      conventional upper gastrointestinal endoscopy.

PMID- 16894312
TI  - The effect of antioxidant supplementation on hepatitis C viral load,
      transaminases and oxidative status: a randomized trial among chronic hepatitis C
      virus-infected patients.
AB  - OBJECTIVE: To assess the effect of antioxidant supplementation on hepatitis C
      viral load, transaminases and oxidative status. METHODS: We performed a
      randomized, placebo-controlled, double-blind trial to assess the effect of
      antioxidant supplementation on serum alanine aminotransferase, plasma hepatitis C
      viral load as well as oxidative and antioxidant markers in patients with
      hepatitis C virus infection. The participants received a daily dose of ascorbic
      acid (500 mg), D-alpha-tocopherol (945 IU) and selenium (200 microg) or placebo
      tablets for 6 months. RESULTS: Twenty-three patients were included. During
      supplementation, the antioxidant group had significantly higher levels of plasma
      ascorbic acid and alpha-tocopherol than the placebo group and the activity of
      erythrocyte glutathione peroxidase had significantly increased from baseline to
      month 6. No differences were observed in serum alanine aminotransferase and log10
      transformed plasma hepatitis C virus-RNA between the groups or changes from the
      baseline at any time. No consistent differences between groups or changes from
      the baseline with respect to erythrocyte activities of antioxidative enzymes
      (glutathione reductase, superoxide dismutase and catalase) or plasma levels of
      oxidative markers (malondialdehyde and 2-amino-adipic semialdehyde) were found.
      CONCLUSION: Supplementation with vitamin C, E and selenium increased the
      antioxidant status, but had no effects on alanine aminotransferase, viral load or
      oxidative markers.

PMID- 16894314
TI  - Analysis of Indian cholesterol gallstones by particle-induced X-ray emission and
      thermogravimetry-derivative thermogravimetry.
AB  - OBJECTIVES: It has been reported that the role of some minor elements plays a
      significant role in the formation of gallstones. The relationship between minor
      and trace element concentrations was established in the present investigation and
      the trace element profile of the current investigation was compared with the
      literature values of south Indian gallstone samples in order to determine their
      possible role in stone formation and growth. The rate of weight loss and
      classification of cholesterol type of gallstones were also investigated by
      thermal analysis. BASIC METHODS: The trace element profile of the cholesterol
      gallstones was determined by proton-induced X-ray emission spectroscopic
      technique and the thermal properties of the cholesterol stones were studied by
      thermogravimetry-derivative thermogravimetry analysis. RESULTS: It was observed
      that 14 minor/trace elements, namely S, Cl, K, Ca, Ti, V, Cr, Mn, Fe, Ni, Cu, Zn,
      Br and Pb, were present in the cholesterol stone samples. The average
      concentration of Fe in south Indian (Chennai region) gallstone samples (503.4
      ppm) is about 2.5 times more than that of the east Indian gallstone samples
      (205.0 ppm), whereas the concentration of Fe is still higher in other parts of
      south India (848.2 ppm) as analysed by Ashok et al. CONCLUSIONS: The higher
      concentration of Cu (in some parts of south India except the Chennai region) and
      Fe in south Indian cholesterol stone samples may be due to the intake of tamarind
      (Garcinia camborginia) as their regular food. The thermogravimetry and derivative
      thermogravimetry curves provided information on the thermal decompositions of
      cholesterol stones.

PMID- 16894313
TI  - Interferon regulatory factor-1 promoter polymorphism and the outcome of hepatitis
      C virus infection.
AB  - OBJECTIVE: Interferon-alpha (IFN-alpha), an important mediator for the host's
      innate antiviral defense system, has been approved for the treatment of
      persistent viral infections. We investigated whether two functional polymorphisms
      in genes involved in IFN-alpha signaling and effector functions are associated
      with the natural outcome of hepatitis C virus (HCV) infection and the
      responsiveness of chronic hepatitis C patients to IFN-alpha therapy. METHODS:
      Forty-four individuals who had resolved HCV infection spontaneously and 147
      patients who developed chronic hepatitis C were analyzed for functional single
      nucleotide polymorphisms in the promoter regions of the interferon regulatory
      factor-1 (IRF-1) and myxovirus resistance protein-1 (MxA) genes at positions -300
      and -88, respectively. RESULTS: With regard to -300 IRF-1 or -88 MxA genotype
      distributions or minor allele frequencies, individuals who spontaneously resolved
      the infection displayed no significant difference compared with those with
      chronic infections. Among patients with chronic infections, however, the -300AA
      IRF-1 genotype, associated with a higher IRF-1 transcriptional activity, was
      absent in patients with chronic HCV genotype 3a infections, with one exception.
      In contrast to expectations, -300AA IRF-1 individuals with HCV genotype 3a
      infection were not represented in higher numbers among those with self-limited
      infections. Regarding IFN-alpha therapy, -300AA IRF-1 chronic hepatitis C
      genotype 1 patients tend to respond more often than those with the other IRF-1
      genotypes. CONCLUSION: Our findings suggest the possibility that the -300AA IRF-1
      genotype is associated with outcome in patients with HCV genotype 3 infection. In
      addition, in HCV genotype-1-infected patients, this genotype appears associated
      with response to therapy.

PMID- 16894315
TI  - Giant fibrovascular polyp of the esophagus.
AB  - Fibrovascular polyps of the esophagus are benign, pedunculated tumors that
      consist mostly of connective tissue and can reach impressive sizes. They arise
      from the upper third of the esophagus and may produce symptoms of dysphagia,
      progressive weight loss and regurgitation. The most serious clinical presentation
      is asphyxia secondary to laryngeal obstruction. Despite their size, diagnosis may
      be difficult. The location of the stalk and the vascularity makes surgical
      resection the preferred mode of removal of these unusual polyps.

PMID- 16894316
TI  - Diffuse large and small bowel necrosis in catastrophic antiphospholipid syndrome.
AB  - The catastrophic variant is an accelerated form of the antiphospholipid syndrome
      resulting in multiorgan failure because of multiple small vessel occlusions. We
      report a case of catastrophic antiphospholipid syndrome in a patient with
      subacute cutaneous lupus erythematosus and ischemic bowel, who presented with
      acute abdominal pain due to diffuse right colon and small bowel necrosis
      requiring large resection, associated with acute respiratory distress syndrome,
      thrombocytopenia and disseminated intravascular coagulation. Histopathological
      examination of resected tissues showed diffuse arteriolar and venous thrombosis
      but no vasculitis, and mesenteric artery lumen severely narrowed by intimal
      fibrosis. The patient died 15 days after admission despite treatment with
      anticoagulation, steroids, continuous hemofiltration and plasma exchange.
      Ischemic bowel and diffuse intestinal necrosis may be secondary to the
      antiphospholipid syndrome, and a high level of suspicion and an early diagnosis
      are required.

PMID- 16894317
TI  - A case of Crohn's disease with hydronephrosis caused by ureteropelvic junction
      obstruction.
AB  - Ureteral obstruction is a rare extraintestinal manifestation of Crohn's disease
      (CD). We report the case of a 20-year-old man who presented with fever,
      diarrhoea, and lower abdominal pain. Diagnostic studies confirmed CD and revealed
      an abdominal mass obstructing the right ureter and hydronephrosis. Ureteropelvic
      junction (UPJ) obstruction was diagnosed. Despite an elemental diet and
      mesalazine therapy, the hydronephrosis persisted, and the patient eventually
      required surgery. Successful laparoscopic pyeloplasty was performed. This is the
      first report of CD associated with UPJ obstruction. Ureteral obstruction as a
      complication of CD is discussed.

PMID- 16894318
TI  - Hepatitis C virus eradication followed by HBeAg to anti-HBe seroconversion after
      pegylated interferon-alpha2b plus ribavirin treatment in a patient with hepatitis
      B and C coinfection.
AB  - In hepatitis B or hepatitis C endemic areas, the number of patients with dual
      infections is substantial. In such patients, interferon-alpha plus ribavirin can
      achieve sustained hepatitis C virus (HCV) clearance and hepatitis B e antigen
      (HBeAg) seroconversion. Pegylated interferon (PegIFN), an established treatment
      for hepatitis C, is currently increasingly recognized as an efficient therapy for
      hepatitis B. No case of successful use of PegIFN plus ribavirin has yet been
      reported, however, in hepatitis B virus (HBV) and HCV coinfection. We report on a
      32-year-old man, of Kampuchean origin, with chronic hepatitis B, as documented by
      the presence of hepatitis B surface antigen with HBeAg, who was coinfected with
      HCV genotype 1. On therapy with PegIFN-alpha2b plus ribavirin, HCV RNA became
      undetectable at week 17. At the end of the 48 weeks of treatment, HCV RNA was
      still undetectable, HBV DNA was reduced and HBeAg remained positive. Twelve weeks
      after the end of treatment, HBV DNA reduction was followed by HBeAg to anti-HBe
      seroconversion. Two years after the end of treatment, HCV RNA and HBV DNA were
      still undetectable, and HBeAg to anti-HBe seroconversion was maintained. We
      conclude that the combination of PegIFN plus ribavirin may induce suppression of
      both viral infections.

PMID- 16894319
TI  - Primary biliary cirrhosis with multinucleated hepatocellular giant cells:
      implications for pathogenesis of primary biliary cirrhosis.
AB  - Histological and clinical features of syncytial giant cell hepatitis (GCH) are
      rarely observed in adults, and the disease has been associated with several
      autoimmune disorders and drug reactions. We describe here the case of a 62-year
      old woman who presented with evidence of severe acute hepatocellular injury and
      cholestasis. Serum work-up demonstrated antimitochondrial antibodies specific for
      primary biliary cirrhosis (PBC) autoantigens, whereas markers of viral infection
      including hepatitis viruses, paramyxovirus and measles virus were negative. Liver
      histology revealed the presence of multinucleated hepatocellular giant cells in
      the parenchymal areas surrounding bridging necrosis. Importantly, damaged
      interlobular bile ducts were also observed within the lymphocyte-infiltrated
      portal tracts. Further study using transmission electron microscopy demonstrated
      the presence of filamentous strands and particles resembling paramyxovirus
      nucleocapsids in the cytoplasm of syncytial giant cells. To our knowledge, this
      is the first case of PBC with histological and clinical evidence of syncytial GCH
      in an adult, and we submit that it might provide novel clues in the enigma of PBC
      pathogenesis.

PMID- 16894321
TI  - Clinical PET in oncology: not only FDG.

PMID- 16894320
TI  - Immunoproliferative small intestinal disease in Greece: presentation of 13 cases
      including two from Albania.
AB  - OBJECTIVES: Immunoproliferative small intestinal disease (IPSID) represents a
      spectrum of clinicopathological entities including alpha-chain disease and other
      types of lymphoplasmacytic proliferations of the lamina propria of the small
      intestine, presenting with severe malabsorption. IPSID has been described mainly
      in the Mediterranean, Middle East, and African countries. It occurs rarely in
      western countries. We present here our experience from Greece describing some
      interesting findings in cases diagnosed during the years 1970-2002. METHODS:
      Current immunological and immunohistochemical methods for the detection of alpha
      heavy chains and the presence of clonality have been used to study 13 cases of
      IPSID diagnosed in Greece, two of whom were Albanian residents. RESULTS: The
      patients were categorized in three subgroups of IPSID: alpha-chain disease (n=8),
      non-alpha chain disease with other monoclonal immunoglobulins (n=3), and
      polyclonal 'non-malignant' IPSID (n=2). In several patients the disease had
      unusual features, and this in some cases delayed the diagnosis. In suspected
      cases it is thus of the utmost importance to proceed to an exploratory
      laparatomy. Patients with stage C disease had a short survival, whereas two
      patients with stage A alpha-chain disease responded to treatment with
      cyclophosphamide, vincristine and prednisolone, and cyclophosphamide,
      doxorubicine, vincristine and prednisolone, respectively, have a disease-free
      long survival of 35 and 12 years, and appear to be cured.

PMID- 16894322
TI  - 99mTc-methylene diphosphonate single photon emission tomography of the knees:
      intensity of uptake and its correlation with arthroscopic findings.
AB  - OBJECTIVE: To examine whether single photon emission computed tomography (SPECT)
      can determine the severity of knee pathology, based on intensity of uptake and,
      therefore, possibly substituting this technique for more invasive and expensive
      diagnostic procedures, such as arthroscopy, in certain patient populations.
      METHODS: The study results of patients referred for knee SPECT followed by an
      arthroscopy at our institution were evaluated retrospectively. The scintigraphic
      and arthroscopic findings for the menisci and femoral condyles were each graded
      on a numeric scale. One numeric scale corresponded to the level of uptake in the
      SPECT and the other to the severity of the pathology visualized at arthroscopy.
      Statistical correlation between both scales, representing the SPECT and
      arthroscopy findings, was performed. RESULTS: Forty-one patients were included in
      the study. A positive and statistically significant correlation was found between
      the intensity of uptake on the SPECT and the severity of the arthroscopic
      findings in the menisci and medial femoral condyle. CONCLUSION: The degree of
      uptake in the knee, as determined by SPECT, positively correlates with the
      severity of pathology seen at arthroscopy. The data can potentially be used to
      assist in decision-making before proceeding to surgery, especially where there is
      severe pathology that may be less amenable to arthroscopic therapy.

PMID- 16894323
TI  - The tissue distribution of Evans blue dye in a sheep model of sentinel node
      biopsy.
AB  - BACKGROUND: Tc-Evans blue is a 'single dose' agent for lymphatic mapping
      combining radioactivity and blue dye for sentinel node identification. The
      mechanism and distribution of blue dye retention in the lymph node is not clearly
      understood. OBJECTIVE: To demonstrate the cellular distribution of Tc-Evans blue
      in sheep sentinel lymph nodes by measuring the radioactivity of different tissue
      components and correlating this with pathological examination. METHODS: Tc-Evans
      blue was used to identify sheep lymph nodes. Part of each node was sent for
      pathological examination including imprint cytology, and frozen and permanent
      section examination. Sections were examined without stains, with only red stains
      and conventional haematoxylin & eosin staining. The remaining nodal tissue was
      homogenized and components separated by enzymatic digestion and density gradient
      centrifugation. Fractions representing each tissue component were counted in a
      gamma counter and the distribution of Tc-Evans blue calculated. RESULTS: A
      dispersed population of blue staining cells was found. Their distribution, number
      and size indicated that they were histiocytes such as macrophages or antigen
      presenting cells. Radioactivity was distributed throughout the lymph node. Over
      70% remained in the plasma, 19% in the leukocyte layer, and 10% was associated
      with erythrocytes and undigested tissue. CONCLUSION: The accumulation of
      radioactivity and blue colour in the lymph nodes indicates the mechanism of
      retention is a result of the binding interaction between Tc-Evans blue-protein
      and lymph node histiocytes including macrophages and antigen presenting cells.

PMID- 16894324
TI  - A technique for analysis of geometric mean renography.
AB  - BACKGROUND AND OBJECTIVES: Renography is used routinely to assess relative right
      to left renal function. Quantification is usually carried out using posterior
      images. Errors in relative renal function may occur if the kidneys are at
      different depths. Geometric mean images from combined anterior and posterior
      views are much less affected by kidney depth and offer the opportunity of more
      accurate and precise quantification. Background subtraction is a key part of the
      analysis process and validated protocols for geometric mean imaging have not been
      devised. This study aims to derive a suitable background subtraction protocol for
      geometric mean imaging. METHODS: Simultaneous anterior and posterior renography
      using Tc mercaptoacetyltriglycine (MAG3) was performed on 16 adults. Analysis was
      carried out using both geometric mean and posterior images. The geometric mean
      background subtraction protocol was modified to give the same results as a
      posterior method, which had previously been validated by correlation with
      measurements of glomerular filtration rate. Absolute and relative uptakes were
      then obtained from both geometric mean and posterior analyses. For each analysis
      values were obtained both with and without depth correction. RESULTS: A revised
      background subtraction protocol for geometric mean renography was devised which
      operated successfully on all studies. Both absolute renal uptake and relative
      function values obtained from geometric mean analysis were not systematically
      different from those obtained using posterior analysis with depth correction.
      Values of the relative renal function from posterior analysis after depth
      correction were closer to the geometric mean values than estimates obtained
      before correction. CONCLUSION: A technique for analysing geometric mean
      renography data has been developed which gives results consistent with a
      previously validated posterior-only method.

PMID- 16894325
TI  - Minimally invasive radio-guided parathyroidectomy: long-term results with the
      'low 99mTc-sestamibi protocol'.
AB  - BACKGROUND: This paper reports the results of minimally invasive radio-guided
      surgery (MIRS) performed in a large group of 280 consecutive patients affected by
      primary hyperparathyroidism (PHPT) and with a high probability of being affected
      by a solitary parathyroid adenoma before surgery. METHODS: The probability of a
      solitary parathyroid adenoma was established by evaluating the patients with a
      single-day imaging protocol based on parathyroid double-tracer scintigraphy and
      high resolution neck ultrasonography. MIRS was performed successfully in 269
      (96.1%) patients. MIRS consisted of a very low dose (37 MBq (1 mCi)) of Tc
      sestamibi, given by intravenous injection, in the operating theatre a few minutes
      before surgery, thus allowing the radiation exposure dose to the patient and
      operating theatre personnel to be minimized (< 1.5 muSv.h to the surgeon).
      RESULTS: No major intraoperative complication was recorded in our series.
      Transient hypocalcaemia was observed in 8% of patients. MIRS required a mean
      duration time of 33 min and a mean hospital stay of 1.2 days. Local anaesthesia
      was successfully performed in 71 patients, 63 of whom were elderly and with
      concomitant invalidating diseases contraindicating general anaesthesia. No case
      of disease relapse was observed during the subsequent follow-up. CONCLUSION: MIRS
      using the 'low sestamibi protocol' is a safe and effective treatment in PHPT
      patients with a high likelihood of a solitary parathyroid adenoma at preoperative
      imaging.

PMID- 16894327
TI  - Quantitative analysis of dopamine synthesis in human brain using positron
      emission tomography with L-[beta-11C]DOPA.
AB  - BACKGROUND AND OBJECTIVES: To estimate the presynaptic function of the central
      dopaminergic system, the rate of endogenous dopamine synthesis has been measured
      by using L-[beta-C]DOPA or 6-[F]fluoro-L-DOPA with positron emission tomography.
      However, the regional kinetics of L-[beta-C]DOPA in human brain have not been
      investigated in detail. In the present study, the regional kinetics of L-[beta
      C]DOPA in normal human brain and the accuracy of the method for quantifying L
      [beta-C]DOPA kinetics, employing reference regions, were investigated. METHODS:
      After intravenous injection of L-[beta-C]DOPA, dynamic scanning was performed on
      ten healthy subjects for 89 min. The overall uptake rate constant K was
      calculated by the kinetic and graphical approaches, in which the occipital cortex
      was used as a reference brain region. RESULTS: Regional distribution of K was
      similar to those of dopamine D2 receptor. A significant negative correlation was
      observed between the neutral amino acid concentration in plasma and the influx
      rate constant through the blood-brain barrier (K1). The K values calculated by
      graphical approach were in good agreement with the values calculated by kinetic
      approach for both experimental and simulated data. CONCLUSIONS: The regional
      distribution of K corresponds to that of the nigrostriatal and mesolimbic
      dopaminergic system. Negative correlation between neutral amino acid
      concentration and K1 supports the suggestion that L-DOPA is transported in a
      competitive fashion via the same carrier system as neutral amino acids at the
      blood-brain barrier. Because the graphical approach can obviate the need for an
      arterial input function, it is useful for investigating the rate of regional
      dopamine synthesis in neuropsychiatric and neurodegenerative diseases.

PMID- 16894326
TI  - Accurate diagnosis of acute pyelonephritis: How helpful is procalcitonin?
AB  - AIM: This prospective study aimed to investigate the diagnostic value of serum
      procalcitonin levels in children with acute pyelonephritis documented by Tc
      dimercaptosuccinic acid (DMSA) scintigraphy. METHODS: We compared the symptoms
      and laboratory findings of fever, vomiting, abdominal/flank pain, leukocyte
      count, serum C-reactive protein and procalcitonin levels with the results of the
      DMSA scan obtained within the first 72 h after referral in children who were
      diagnosed as having acute pyelonephritis. Thirty-three children (31 female and
      two male) aged 1-11 years (mean 4.42 years) were enrolled in this prospective
      study. RESULTS: Twenty-one of 33 patients (64%) had positive DMSA scans. On the
      scans obtained after 6 months, five of 21 patients (23.8%) had renal scars. No
      correlation was found between clinical and laboratory parameters, alone or
      combined with each other, and positive DMSA scans. Serum procalcitonin levels
      were 0.767+/-0.64 and 1.23+/-1.17 ng . ml in children with normal and positive
      DMSA scans, respectively. The cut-off value for procalcitonin using receiver
      operating characteristic analysis was 0.9605 ng . ml, while sensitivity and
      specificity were 86.4% and 36.4%, respectively. However, if the cut-off value was
      chosen as 2 ng . ml, the sensitivity increased to 100% while specificity did not
      change markedly. CONCLUSION: The serum procalcitonin test, like other commonly
      used laboratory parameters, e.g. serum C-reactive protein and white blood cell
      count, was inadequate in distinguishing renal parenchymal involvement in acute
      febrile urinary tract infections.

PMID- 16894328
TI  - Value of 99mTc-TRODAT-1 SPECT to predict clinical response to methylphenidate
      treatment in adults with attention deficit hyperactivity disorder.
AB  - BACKGROUND: In a previous study, binding of Tc-TRODAT-1 to the dopamine
      transporter (DAT) was found to be higher in patients with attention deficit
      hyperactivity disorder (ADHD) as compared to healthy controls. AIM: To determine
      whether the degree of Tc-TRODAT-1 binding to the striatal DAT may have a
      predictive role on the response to methylphenidate (MPH) in patients with ADHD.
      METHODS: Twenty-two adult patients suffering from ADHD underwent a brain SPECT
      scan with Tc-TRODAT-1. After the scan patients received MPH, individually
      medicated up to 60 mg.day. Severity of illness was estimated using the Clinical
      Global Impression (CGI-S) Scale before treatment. Ten weeks after the beginning
      of MPH treatment the improvement in global symptoms was rated by the Clinical
      Global Improvement Scale (CGI-I). RESULTS: Before treatment 17/22 patients with
      ADHD presented with higher striatal DAT binding as compared to age-matched
      healthy controls (+23.8%; P<0.01). After treatment with MPH a significant
      improvement of ADHD symptoms was demonstrated by the CGI-I in 16 of these 17
      patients (CGI-S before: 4.8; CGI-I after MPH: 1.9; P<0.01). Five patients showed
      reduced DAT binding prior to therapy (-14.4%; P=0.04); these patients did not
      respond to MPH therapy (CGI-S before: 4.5; CGI-I after MPH: 4.2; P=0.40).
      CONCLUSION: Our findings suggest that ADHD patients with primarily elevated
      binding of Tc-TRODAT-1 to the striatal DAT responded better to therapy with MPH
      as compared to those with normal or low DAT binding. Consequently, our results -
      even if obtained on a small collective indicate that measurement of DAT may be an
      important prognostic predictor for therapy response to MPH.

PMID- 16894329
TI  - Evaluation of a new expert system for fully automated detection of the
      Alzheimer's dementia pattern in FDG PET.
AB  - OBJECTIVE: Fluorodeoxyglucose (FDG) positron emission tomography (PET) is
      increasingly used to support a diagnosis of Alzheimer's disease. The aim of the
      present study was to evaluate a new expert system (PALZ) for the fully automated
      analysis of FDG PET images for diagnosis of the disease. METHODS: The PALZ tool
      is based on the detection of the typical disease pattern in FDG PET images. Its
      potential for this task was evaluated in 22 consecutive patients with suspected
      Alzheimer's disease who had been graded as positive for the pattern by an
      experienced reader (visual analysis supported by statistical parametric mapping
      (SPM)), and in 18 controls. Dependence on scanner performance was assessed by
      variation of the spatial resolution of the PET images. RESULTS: All the
      Alzheimer's disease subjects were classified as pattern-positive by the PALZ
      tool. Fifteen controls were classified as normal. Sensitivity and specificity for
      differentiation of the patients with suspected Alzheimer's disease from the
      controls were 100% and 83%, respectively. The false positive finding in three
      controls most likely was caused by differences in attenuation correction between
      the normal data base of the PALZ tool (cold transmission scan) and the local data
      sets (hot transmission scan). There was only mild dependence on spatial
      resolution. CONCLUSIONS: The results of the present study suggest that the PALZ
      tool provides similar performance for the detection of the typical Alzheimer's
      disease pattern in FDG PET images as an experienced reader supported by SPM. The
      PALZ tool is fully automated, easy to use, and insensitive to the spatial
      resolution of the PET scanner used. Therefore, it has the potential for
      widespread clinical use.

PMID- 16894330
TI  - The diabetic foot: Charcot joint and osteomyelitis.
AB  - Foot problems are common causes of disability in diabetic patients with as many
      as 25% expected to develop severe foot or leg problems during their lifetimes.
      Although skin ulceration is the most frequent problem, bones may also be involved
      in two different clinical conditions: osteomyelitis and Charcot osteoarthropathy.
      Osteomyelitis causes complications in up to one third of diabetic foot infections
      and is due to direct contamination from a soft-tissue ulcer. Osteoarthropathy
      Charcot foot is a chronic and progressive disease of the bone and joints. Both
      osteomyelitis and Charcot joint are conditions with an increased risk of lower
      limb amputation, both may have a successful outcome when recognized and treated
      in the early stages. The major diagnostic difficulty is in distinguishing bone
      infection (osteomyelitis) from non-infectious neuropathic bony disorders as in
      osteoarthropathy Charcot foot. An additional difficulty is found when a bone
      infection superimposes a Charcot osteopathy. This condition, which can be
      clinically suspected when foot ulceration appears in Charcot foot, needs to be
      diagnosed because it implies a different therapeutic strategy. This article aims
      to summarize both these two clinical conditions and give indications to make a
      timely and correct diagnosis.

PMID- 16894332
TI  - Effects of intranasal 17beta-estradiol administration on serum bioactive
      interleukin-6 and C-reactive protein levels in healthy postmenopausal women.
AB  - OBJECTIVE: Oral estrogen increases the levels of C-reactive protein (CRP), which
      is an independent risk factor for coronary heart disease in healthy individuals.
      The aim of our study was to investigate the effects of intranasal 17beta
      estradiol (E2) on serum CRP and its most potent stimulant, interleukin-6 in
      healthy postmenopausal women. DESIGN: Thirty-six healthy postmenopausal women (45
      54 y) were enrolled. According to their individual preferences, they were
      assigned to intranasal (n = 10), transdermal (n = 14), or oral (n = 12)
      continuous E2 treatment with a sequential progestin (10-14 d in a 28-d cycle).
      Blood samples were drawn at baseline and after 3, 6, and 12 months during the
      estrogen-only phase to adjust for the progestin effect. RESULTS: In women taking
      intranasal or transdermal E2, there were no significant changes in median serum
      CRP levels during the 12-month treatment period. In women taking oral E2
      preparations, serum median CRP levels were significantly higher compared to
      baseline after 6 and 12 months of the therapy (P < 0.05). Conversely, serum
      median bioactive interleukin-6 levels were significantly lower after 6 and 12
      months in women taking E2 intranasally or orally and after 12 months in women
      taking E2 transdermally (P < 0.05). CONCLUSIONS: The results of our study show
      that intranasal, similarly to transdermal, E2 administration does not increase
      serum CRP levels in postmenopausal women. They also support the hypothesis that
      CRP increase during oral estrogen treatment is not mediated by the enhancement of
      interleukin-6 production by the immune cells but is rather caused by the hepatic
      first-pass metabolism effect.

PMID- 16894333
TI  - Lidocaine pharmacokinetics in postmenopausal women on hormone therapy.
AB  - OBJECTIVE: The study was designed to evaluate the effect of hormone therapy (HT)
      preparations containing 17beta-estradiol and micronized progesterone administered
      orally and transdermally on the pharmacokinetics of lidocaine, a probe drug that
      is metabolized by liver oxidative pathways involving cytochrome P-450 1A2 and 3A4
      (CYP1A2 and CYP3A4). DESIGN: The study was carried out in 18 postmenopausal women
      divided into two groups administered HT for 6 months: group 1, 17beta-estradiol
      (orally) and micronized progesterone sublingually; and group 2, 17beta-estradiol
      (transdermally) and micronized progesterone sublingually. Pharmacokinetic study
      with intravenous lidocaine (1 mg/kg) and blood sampling during 360 minutes from
      injection was performed before the HT initiation and after 3 and 6 months of HT.
      RESULTS: Pharmacokinetic parameters of lidocaine demonstrated accelerated drug
      elimination in women on oral HT after 3 months. A significant reduction of area
      under the curve by 15.0% (P < 0.05), shortening of t(1/2) by 15.2% (P < 0.05),
      increase of lambda(z) by 10.0% (P < 0.05), and Cl/BW by 14.3% (P < 0.05) were
      observed. In contrast, transdermal administration of HT did not influence
      pharmacokinetic parameters of the drug. The effects of oral HT were not seen 6
      months after the start of HT. CONCLUSION: HT can influence the pharmacokinetics
      of lidocaine, ie, its hepatic metabolism, through CYP3A4 and CYP1A2. The effect
      depends on the route of administration and therapy duration.

PMID- 16894335
TI  - Efficacy and safety of a special extract of Rheum rhaponticum (ERr 731) in
      perimenopausal women with climacteric complaints: a 12-week randomized, double
      blind, placebo-controlled trial.
AB  - OBJECTIVE: To investigate the efficacy and safety of the special extract ERr 731
      from the roots of Rheum rhaponticum compared to placebo in perimenopausal women
      with climacteric complaints. DESIGN: A multicenter, prospective, randomized,
      double-blind, placebo-controlled, clinical trial in which 109 women with
      climacteric complaints received either one enteric-coated tablet of ERr 731 (n =
      54) or placebo (n = 55) daily for 12 weeks. Primary outcome criterion for
      efficacy was the change in Menopause Rating Scale II (MRS II) total score after
      12 weeks. Other efficacy assessments analyzed number and severity of hot flushes,
      menopause-specific quality of life, number of bleeding/spotting days, and
      treatment outcome. RESULTS: By 12 weeks, the MRS II total score and each MRS II
      symptom significantly decreased in the ERr 731 group compared to the placebo
      group (P < 0.0001). After 4 weeks, ERr 731 also significantly decreased the
      number and severity of hot flushes (P < 0.0001). After 12 weeks, the overall
      menopause-specific quality of life was significantly better in women treated with
      ERr 731 compared with placebo (P < 0.05). Treatment outcome assessed by
      investigators and participants was better in the ERr 731 group, and ERr 731 was
      better tolerated than placebo. There were no differences in gynecological
      findings including endometrial biopsies, bleeding, weight, blood pressure, pulse,
      and laboratory safety parameters between the treatment groups. No adverse events
      were classified as being related to the investigational medication. CONCLUSIONS:
      Compared to placebo, ERr 731 significantly reduces the occurrence and severity of
      climacteric complaints in perimenopause. It is also safe and well tolerated.

PMID- 16894334
TI  - Escitalopram versus ethinyl estradiol and norethindrone acetate for symptomatic
      peri- and postmenopausal women: impact on depression, vasomotor symptoms, sleep,
      and quality of life.
AB  - OBJECTIVE: To examine the efficacy and tolerability of escitalopram (ESCIT)
      compared to estrogen and progestogen therapy (EPT) for the treatment of
      symptomatic peri- and postmenopausal women. DESIGN: Forty women (aged 40-60
      years) with depressive disorders and menopause-related symptoms were randomly
      assigned to an 8-week open trial with ESCIT (flexible dose, 10-20 mg/day; fixed
      dose, 10 mg/day for the first 4 weeks) or estrogen plus progestogen therapy
      (ethinyl estradiol 5 microg/day plus norethindrone acetate 1 mg/day). Primary
      outcome measures included Montgomery-Asberg Depression Rating Scale and the
      Greene Climacteric Scale at week 8. Secondary outcome measures included the
      Clinical Global Impressions as well as sleep and quality of life assessments.
      RESULTS: Thirty-two women (16 on EPT, 16 on ESCIT) were included in the analyses.
      Full remission of depression (score of <10 on the Montgomery-Asberg Depression
      Rating Scale) was observed in 75% (12/16) of subjects treated with ESCIT,
      compared to 25% (4/16) treated with EPT (P = 0.01, Fisher's exact tests).
      Remission of menopause-related symptoms (>50% decrease in Greene Climacteric
      Scale scores) was noted in 56% (9/16) of women treated with ESCIT compared to
      31.2% (5/16) on EPT (P = 0.03, Pearson's chi2 tests). Improvement in sleep, hot
      flashes, and quality of life was observed with both treatments. CONCLUSIONS:
      ESCIT is more efficacious than EPT for the treatment of depression and has a
      positive impact on other menopause-related symptoms. ESCIT may constitute a
      treatment option for symptomatic menopausal women who are unable or unwilling to
      use hormone therapy.

PMID- 16894336
TI  - Different effects of tibolone and low-dose EPT in the management of
      postmenopausal women with primary headaches.
AB  - OBJECTIVE: The present randomized prospective study aimed to compare the effect
      of tibolone (T) with conventional low-dose estrogen-progestogen therapy (EPT)
      administered in a combined continuous regimen on the course of primary headaches
      in postmenopausal women requesting hormone therapy (HT) for climacteric
      complaints. DESIGN: Forty women presenting for clinical evaluation of headache
      (migraine without aura and episodic tension-type headache) were enrolled. The
      observational period lasted 7 months during which women kept a diary of the
      clinical characteristics of headache attacks and analgesic use. Climacteric
      symptoms and both anxiety and depression were also measured. After a 1-month run
      in period, women received two different HT regimens: 1 mg 17beta-estradiol + 0.5
      mg norethisterone acetate (EPT) or 2.5 mg T. Follow-up evaluations were planned
      after 3 and 6 months of treatment. RESULTS: Although T did not affect the number
      of days with migraine without aura, it significantly reduced the number of hours
      during which pain intensity prohibited daily activities (P < 0.001) and the
      number of analgesics (P < 0.001) after 3 months. Conventional low-dose EPT
      administered in a combined continuous regimen was confirmed to have a mild, but
      negative, effect on the course of migraine without aura by increasing the number
      of days with head pain (P < 0.001) and the number of analgesics (P < 0.001).
      Interestingly, both treatments were effective in the management of episodic
      tension-type headache, significantly reducing the number of days with head pain,
      severity, and analgesic consumption. CONCLUSIONS: In postmenopausal headache
      sufferers, analgesics are more effective in alleviating severe head pain when
      women are treated with T in comparison with low-dose EPT for climacteric
      complaints.

PMID- 16894337
TI  - Relationship between health-related quality of life domains and bone status in
      postmenopausal Japanese women.
AB  - OBJECTIVE: To assess the relationship between health-related quality of life
      domains and bone status, including bone metabolism, in postmenopausal Japanese
      community women. DESIGN: The study subjects were 88 women who were participants
      in a screening program for osteoporosis in 2003 without a history of mental
      disorders, metabolic disorders, smoking, bone fractures, and/or estrogen
      treatment. The participation rate was 75.9%. The age range was 50 to 68 years
      (mean, 57), and body mass index (BMI) ranged from 15.7 to 36.6 (mean, 22.4).
      Health-related quality of life domains were evaluated using the Medical Outcomes
      Study Short-Form 36 Health Survey, and bone mineral content was measured by
      quantitative ultrasound of the calcaneus. Serum total osteocalcin and serum N
      telopeptide were measured by enzyme-linked immunosorbent assay. Multiple linear
      regression models were used to study the association of age, BMI, and eight
      health-related quality of life domains as independent variables in age-corrected
      bone status and markers of bone turnover as dependent ones. RESULTS: The
      participants' calcaneal Z scores by quantitative ultrasound ranged from -2.14 to
      2.71. The mean Z score was -0.17 (-0.27, -0.07). Multiple regression analysis
      revealed that BMI (P < 0.05), physical function (P < 0.01), and role-emotional
      (role limitations caused by emotional problems) (P < 0.01) were factors in
      increasing bone mineral content. Also, a positive relationship was found between
      vitality (P < 0.01), social function (P < 0.05), and total osteocalcin.
      CONCLUSIONS: Although causality is not clear, in addition to low BMI, role
      limitations due to poor emotional status and low physical function are related to
      low bone mineral content in postmenopausal Japanese community women. These
      results imply that when we are concerned about osteoporosis in postmenopausal
      women, we should pay attention not only to their physical function but also to
      their psychological state.

PMID- 16894338
TI  - Breaching the great wall: peptidoglycan and microbial interactions.
AB  - Once thought to be a process that occurred only in a few human pathogens, release
      of biologically active peptidoglycan fragments during growth by Gram-negative
      bacteria controls many types of bacterial interaction, including symbioses and
      interactions between microorganisms. This Perspective explores the role of
      peptidoglycan fragments in mediating a range of microbial-host interactions, and
      discusses the many systems in which peptidoglycan fragments released during
      bacterial growth might be active.

PMID- 16894339
TI  - Sensing by bacterial regulatory systems in host and non-host environments.
AB  - Free-living organisms have the ability to gauge their surroundings and modify
      their gene expression patterns in ways that help them cope with new environments.
      Here we discuss the physiological significance of recent reports describing the
      ability of the Salmonella typhimurium PhoP/PhoQ two-component system to recognize
      and respond to host-derived antimicrobial peptides.

PMID- 16894340
TI  - The genomic code: inferring Vibrionaceae niche specialization.
AB  - The Vibrionaceae show a wide range of niche specialization, from free-living
      forms to those attached to biotic and abiotic surfaces, from symbionts to
      pathogens and from estuarine inhabitants to deep-sea piezophiles. The existence
      of complete genome sequences for closely related species from varied aquatic
      niches makes this group an excellent case study for genome comparison.

PMID- 16894341
TI  - Fundamental processes in the evolutionary ecology of Lyme borreliosis.
AB  - The evolutionary ecology of many emerging infectious diseases, particularly
      vector-borne zoonoses, is poorly understood. Here, we aim to develop a
      biological, process-based framework for vector-borne zoonoses, using Borrelia
      burgdorferi sensu lato (s.l.), the causative agent of Lyme borreliosis in humans,
      as an example. We explore the fundamental biological processes that operate in
      this zoonosis and put forward hypotheses on how extrinsic cues and intrinsic
      dynamics shape B. burgdorferi s.l. populations. Additionally, we highlight
      possible epidemiological parallels between B. burgdorferi s.l. and other vector
      borne zoonotic pathogens, including West Nile virus.

PMID- 16894342
TI  - Antiangiogenic therapies in endometriosis.
AB  - Oral contraceptives, androgenic agents, progestins and gonadotropin-releasing
      hormone analogues have all been successfully used in the treatment of
      endometriosis. However, none of these drugs can eradicate the disease. It is
      widely accepted that the growth of newly formed blood vessels is essential for
      the establishment and growth of endometriotic lesions; therefore, inhibition of
      angiogenesis may offer a new option for treatment of this disorder. In this
      paper, we reviewed anti-vascular endothelial growth factor agents and other
      angiostatic drugs (i.e., TNP470, endostatin, anginex, rapamycin) that have been
      studied in laboratory and animal models of endometriosis. Although preliminary
      results are interesting, further investigations are required before clinical
      trials can be planned in humans.

PMID- 16894343
TI  - Rapamycin induces regression of endometriotic lesions by inhibiting
      neovascularization and cell proliferation.
AB  - BACKGROUND AND PURPOSE: Rapamycin is a widely used drug with antifungal,
      immunosuppressant and antiangiogenic effects. Herein, we studied whether
      immunosuppressive doses of rapamycin are capable of influencing endometriotic
      lesions. EXPERIMENTAL APPROACH: We tested in vitro the potential of rapamycin to
      inhibit endothelial cell sprouting using the aortic ring assay and we further
      studied its effect on the expression of proliferating cell nuclear antigen
      (PCNA), apoptotic cell death-associated activated caspase-3 and vascular
      endothelial growth factor (VEGF) in cultured endometrial tissue fragments. In
      addition, we analyzed the drug in vivo after induction of endometriotic lesions
      by transplanting isolated endometrial fragments into the dorsal skinfold chamber
      of Syrian golden hamsters. Using intravital fluorescence microscopy, we
      repetitively analyzed angiogenesis, neovascularization and microcirculatory
      parameters over a time period of 14 days in rapamycin-treated animals and DMSO
      treated controls. KEY RESULTS: Administration of rapamycin significantly reduced
      the size of the endometriotic lesions. This was associated by inhibition of VEGF
      mediated angiogenesis as indicated by a suppression of endothelial cell sprouting
      in vitro and a reduction of microvessel density in endometriotic lesions in vivo.
      Moreover, rapamycin directly inhibited cell proliferation within endometrial
      tissue, while manifestation of apoptotic cell death remained unaffected.
      CONCLUSIONS AND IMPLICATIONS: Our data indicate that administration of rapamycin
      may represent a novel therapeutic approach for an antiangiogenic treatment of
      endometriosis.

PMID- 16894344
TI  - The effects of cardamonin on lipopolysaccharide-induced inflammatory protein
      production and MAP kinase and NFkappaB signalling pathways in
      monocytes/macrophages.
AB  - BACKGROUND AND PURPOSE: In this study we examined the effect of the natural
      product cardamonin, upon lipopolysaccharide (LPS)-induced inflammatory gene
      expression in order to attempt to pinpoint the mechanism of action. EXPERIMENTAL
      APPROACHES: Cardamonin was isolated from the Greek plant A. absinthium L. Its
      effects were assessed on LPS-induced nitrite release and iNOS and COX-2 protein
      expression in two macrophage cell lines. Western blotting was used to investigate
      its effects on phosphorylation of the mitogen activated protein (MAP) kinases,
      ERK, JNK and p38 MAP kinase, and activation of the NFkappaB pathway, at the level
      of IkappaBalpha degradation and phosphorylation of NFkappaB. Also its effects on
      NFkappaB and GAS/GAF-DNA binding were assessed by EMSA. KEY RESULTS: Cardamonin
      concentration-dependently inhibited both NO release and iNOS expression but had
      no effect on COX-2 expression. It did not affect phosphorylation of the MAP
      kinases, degradation of IkappaBalpha or phosphorylation of NFkappaB. However, it
      inhibited NFkappaB DNA-binding in both LPS-stimulated cells and nuclear extracts
      of the cells (in vitro). It also inhibited IFNgamma-stimulated iNOS induction and
      GAS/GAF-DNA binding. CONCLUSIONS AND IMPLICATIONS: These results show that the
      inhibitory effect of cardamonin on LPS-induced iNOS induction is not mediated via
      effects on the initial activation of the NFkappaB or MAP kinase pathways but is
      due to a direct effect on transcription factor binding to DNA. However, although
      some selectivity in cardamonin's action is implicated by its inability to affect
      COX-2 expression, its exact mechanism(s) of action has yet to be identified.

PMID- 16894346
TI  - Mutations within the selectivity filter of the NMDA receptor-channel influence
      voltage dependent block by 5-hydroxytryptamine.
AB  - BACKGROUND AND PURPOSE: Voltage-dependent block by Mg2+ is a cardinal feature of
      NMDA receptors which acts as a coincidence detector to prevent the receptor from
      over-activation. Inhibition of NMDA receptor currents by 5-hydroxytryptamine (5
      HT) indicated that 5-HT, similar to Mg2+, binds within the membrane electric
      field. In the present study, we assessed whether point mutations of critical
      asparagine residues located within the selectivity filter of NR1 and NR2A
      subunits of NMDA receptor-channel affect voltage-dependent block by 5-HT.
      EXPERIMENTAL APPROACH: The mode of action of 5-HT and Mg2+ on wild-type and
      mutated NMDA receptor-channels expressed in Xenopus oocytes was investigated
      using the two-electrode voltage clamp recording technique. KEY RESULTS: The
      mutation within the NR1 subunit NR1(N0S or N0Q) strongly reduced the voltage
      dependent block by 5-HT and increased the IC50. The corresponding mutations
      within the NR2 subunits NR2A(N0Q or N+1Q) reduced the block by 5-HT to a lesser
      extent. This is in contrast to the block produced by external Mg2+ where a
      substitution at the NR2A(N0) and NR2A(N+1) sites but not at the NR1(N0) site
      significantly reduced Mg2+ block. CONCLUSION AND IMPLICATIONS: The block of NMDA
      receptor-channels by 5-HT depends on the NR1-subunit asparagine residue and to a
      lesser extent on the NR2A-subunit asparagine residues. These data suggest that
      the interaction of 5-HT with functionally important residues in a narrow
      constriction of the pore of the NMDA receptor-channel provides a significant
      barrier to ionic fluxes through the open channel due to energetic factors
      governed by chemical properties of the binding site and the electric field.

PMID- 16894345
TI  - Muscarinic receptor-activated cationic channels in murine ileal myocytes.
AB  - BACKGROUND AND PURPOSE: There is little information about the excitatory
      cholinergic mechanisms of mouse small intestine although this model is important
      for gene knock-out studies. EXPERIMENTAL APPROACH: Using patch-clamp techniques,
      voltage-dependent and pharmacological properties of carbachol- or intracellular
      GTPgammaS-activated cationic channels in mouse ileal myocytes were investigated.
      KEY RESULTS: Three types of cation channels were identified in outside-out
      patches (17, 70 and 140 pS). The voltage-dependent behaviour of the 70 pS
      channel, which was also the most abundantly expressed channel (approximately 0.35
      micro(-2)) was most consistent with the properties of the whole-cell muscarinic
      current (half-maximal activation at -72.3+/-9.3 mV, slope of -9.1+/-7.4 mV and
      mean open probability of 0.16+/-0.01 at -40 mV; at near maximal activation by 50
      microM carbachol). Both channel conductance and open probability depended on the
      permeant cation in the order: Cs+ (70 pS) >Rb+ (66pS) >Na+ (47 pS) >Li+ (30 pS).
      External application of divalent cations, quinine, SK&F 96365 or La3+ strongly
      inhibited the whole-cell current. At the single channel level the nature of the
      inhibitory effects appeared to be very different. Either reduction of the open
      probability (quinine and to some extent SK&F 96365 and La3+) or of unitary
      current amplitude (Ca2+, Mg2+, SK&F 96365, La3+) was observed implying
      significant differences in the dissociation rates of the blockers. CONCLUSIONS
      AND IMPLICATIONS: The muscarinic cation current of murine small intestine is very
      similar to that in guinea-pig myocytes and murine genetic manipulation should
      yield important information about muscarinic receptor transduction mechanisms.

PMID- 16894347
TI  - Regulation of the common carotid arterial blood flow by nicotinic receptors in
      the medulla of cats.
AB  - BACKGROUND AND PURPOSE: Actions of glutamate and serotonin on their respective
      receptors in the dorsal facial area (DFA) of the medulla are known to regulate
      common carotid arterial (CCA) blood flow in cats. Less is known about
      acetylcholine action on its nicotinic receptor (nAChR) subtypes in the DFA for
      regulation of CCA blood flow and this aspect was investigated. EXPERIMENTAL
      APPROACH: Nicotinic and muscarinic agonists and antagonists were microinjected
      into the DFA through a three-barrel tubing in anesthetized cats. RESULTS: CCA
      blood flow was dose-dependently increased by nicotine (a non-selective nAChR
      agonist) and choline (a selective alpha7-nAChR agonist). These effects of
      nicotine were attenuated by alpha-bungarotoxin (an alpha7-nAChR antagonist),
      methyllycaconitine (an alpha7-nAChR antagonist), mecamylamine (a relatively
      selective alpha3beta4-nAChR antagonist) and dihydro-beta-erythroidine (a
      relatively selective alpha4beta2-nAChR antagonist). The choline-induced flow
      increase was attenuated by alpha-bungarotoxin and mecamylamine, but not by
      dihydro-beta-erythroidine. Muscarinic agonists (muscarine and methacholine) and
      antagonist (atropine) affected neither the basal nor the nicotine-induced
      increase in the CCA blood flow. CONCLUSIONS AND IMPLICATIONS: Functional alpha7,
      alpha4beta2, and alpha3beta4 subunits of the nAChR appear to be present on the
      DFA neurons. Activations of these receptors increase the CCA blood flow. The
      present findings do not preclude the presence of other nAChRs subunits.
      Muscarinic receptors, if any, on the DFA are not involved in regulation of the
      CCA blood flow. Various subtypes of nAChRs in the DFA may mediate regulation of
      the CCA and cerebral blood flows.

PMID- 16894348
TI  - Kinase-dependent, retinoic acid receptor-independent up-regulation of
      cyclooxygenase-2 by all-trans retinoic acid in human mesangial cells.
AB  - BACKGROUND AND PURPOSE: Preliminary results in human mesangial cells (MC)
      suggested that all-trans retinoic acid (ATRA) increased the expression of COX-2
      and the production of prostaglandin E2 (PGE2), a PG with anti-inflammatory
      effects in MC. The aim of this work is to confirm that ATRA increases the
      expression of COX-2 in MC and to examine the mechanisms involved. EXPERIMENTAL
      APPROACH: Cultured MC were treated with ATRA. COX expression and kinase activity
      were analyzed by Western blot. Transcriptional mechanisms were analyzed by
      Northern blot, RT-PCR and promoter assays. KEY RESULTS: COX-2 and COX-1
      expression and PGE2 production were increased by ATRA. COX-2 played a role in
      PGE2 production as production was only partially inhibited by COX-1 inhibitor SC
      560. COX-2 up-regulation by ATRA was due to transcriptional mechanisms as pre
      incubation with actinomycin D abolished it and ATRA increased the expression of
      COX-2 mRNA and the activity of a human COX-2 promoter construct, whereas post
      transcriptional mechanisms were not found. Retinoic acid receptors (RAR) were not
      involved in the up-regulation of COX-2 by ATRA since it was not inhibited by RAR
      pan-antagonists and the RAR-pan-agonist TTNPB did not up-regulate COX-2. Instead
      ATRA might act through a sustained activation of extracellular signal-regulated
      kinase 1/2 (ERK1/2) since up-regulation of COX-2 was prevented by inhibition of
      the activation of ERK1/2 with PD098059. Also ERK1/2, as well as downstream
      signalling proteins from ERK1/2, remained phosphorylated when COX-2 increased 24
      h later. CONCLUSIONS AND IMPLICATIONS: These results highlight the relevance of
      RAR-independent mechanisms to the biological effects of ATRA.

PMID- 16894349
TI  - In vitro pharmacological characterization of AM1241: a protean agonist at the
      cannabinoid CB2 receptor?
AB  - BACKGROUND AND PURPOSE: The CB2 receptor has been proposed as a novel target for
      the treatment of pain, and CB2 receptor agonists defined in in vitro assays have
      demonstrated analgesic activity in animal models. Based on its in vivo analgesic
      efficacy, AM1241 has been classified as a CB2-selective agonist. However, in
      vitro characterization of AM1241 in functional assays has not been reported.
      EXPERIMENTAL APPROACH: In this study, AM1241 was characterized across multiple in
      vitro assays employing heterologous recombinant receptor expression systems to
      assess its binding potencies at the human CB2 and CB1 receptors and its
      functional efficacies at the human CB2 receptor. KEY RESULTS: AM1241 exhibited
      distinct functional properties depending on the assay conditions employed, a
      unique profile in contrast to those of the agonist CP 55,940 and the inverse
      agonist SR144528. AM1241 displayed neutral antagonist activities in FLIPR and
      cyclase assays. However, when cyclase assays were performed using lower forskolin
      concentrations for stimulation, AM1241 exhibited partial agonist efficacy. In
      addition, it behaved as a partial agonist in ERK (or MAP) kinase assays.
      CONCLUSIONS AND IMPLICATIONS: The unusual phenomenon of inconsistent functional
      efficacies suggests that AM1241 is a protean agonist at the CB2 receptor. We
      postulate that functional efficacies displayed by protean agonists in various
      assay systems may depend on the levels of receptor constitutive activities
      exhibited in the assay systems, and therefore, efficacies observed in in vitro
      assays may not predict in vivo activities.

PMID- 16894350
TI  - Obesity--a risk factor or a RISK factor for myocardial infarction?
AB  - The detrimental actions of leptin on cardiovascular function are well
      established. Smith et al. report the novel finding of a reduction of infarct size
      by exogenous leptin when given at reperfusion. The involvement of the reperfusion
      injury salvage kinase (RISK) pathway in such reduction of infarct size and its
      relation to ischemic pre- and postconditioning are discussed and some
      methodological issues in its assessment are raised. Obesity has possibly opposite
      effects on the incidence and outcome of myocardial infarction.

PMID- 16894352
TI  - ADAM15 upregulation and interaction with multiple binding partners in
      inflammatory bowel disease.
AB  - A disintegrin and metalloproteinase (ADAM)15 is upregulated in some tissues
      undergoing remodeling. This glycoprotein is characterized by adhesive function
      through its interaction with members of the integrin family and protease
      properties. The goal of this work was to describe the tissue distribution of
      ADAM15 and its spatial relationship with its known binding partners in
      inflammatory bowel disease. ADAM15 expression was examined using frozen tissues
      from eight patients with ulcerative colitis or Crohn's disease and four normal
      colons by immunohistochemistry, immunoblotting and quantitative reverse
      transcription-polymerase chain reaction. In addition expression of alpha5beta1-
      and alphavbeta3-integrins, VE-cadherin, alpha-smooth muscle actin (alpha-SMA) and
      collagen IV was examined using immunohistochemistry and confocal microscopy. In
      the normal colon, ADAM15 was expressed by all epithelial cells throughout the
      crypt and by pericryptic myofibroblasts coexpressing alpha-SMA and collagen IV.
      ADAM15 was also expressed by endothelial cells and vascular myocytes in all
      layers of the intestinal wall as well as by nonvascular myocytes of the
      muscularis mucosae and muscularis propria. In inflammatory bowel diseases, ADAM15
      was strongly upregulated at the mRNA level and expressed only as an active form
      as shown by immunoblotting analysis. Parallel to its upregulation, ADAM15
      expression was found both at the plasma membrane and in the cytoplasm of
      epithelial cells in acute attacks of the disease. In the crypt abcesses, ADAM15
      positive epithelial cells were in close contact with alpha5beta1-integrin
      positive leukocytes localized between these cells and in the crypt lumen. In the
      regenerative areas, ADAM15-positive epithelial cells were in close contact with
      alpha5beta1- and alphavbeta3-positive pericryptic myofibroblasts. In endothelial
      cells, VE-cadherin was decreased. In contrast, ADAM15 was strongly expressed by
      endothelial cells and was in close contact with alpha5beta1-positive leukocytes.
      There is a differential expression of ADAM15 in epithelial cells during
      inflammatory bowel disease compared with the normal colon. In addition, the
      spatial relationships with its binding partners suggest a role for ADAM15 in the
      differentiation of regenerative colonic mucosa as well as in leukocyte
      transmigration across epithelial and endothelial barriers.

PMID- 16894351
TI  - The antiepileptic and anticancer agent, valproic acid, induces P-glycoprotein in
      human tumour cell lines and in rat liver.
AB  - BACKGROUND AND PURPOSE: The antiepileptic drug valproic acid, a histone
      deacetylase (HDAC) inhibitor, is currently being tested as an anticancer agent.
      However, HDAC inhibitors may interact with anticancer drugs through induction of
      P-glycoprotein (P-gp, MDR1) expression. In this study we assessed whether
      valproic acid induces P-gp function in tumour cells. We also investigated effects
      of valproic acid on the mRNA for P-gp and the cytochrome P450, CYP3A, in rat
      livers. EXPERIMENTAL APPROACH: Effects of valproic acid on P-gp were assessed in
      three tumour cell lines, SW620, KG1a and H4IIE. Accumulation of acetylated
      histone H3 in rats' livers treated for two or seven days with valproic acid was
      evaluated using a specific antibody. Hepatic expression of the P-gp genes, mdr1a,
      mdr1b and mdr2, was determined by real-time polymerase chain reaction. The
      effects of valproic acid on CYP3A were assessed by Northern blot analysis and
      CYP3A activity assays. KEY RESULTS: Valproic acid (0.5-2.0 mM) induced P-gp
      expression and function up to 4-fold in vitro. The effect of a series of valproic
      acid derivatives on P-gp expression in SW620 and KG1a cells correlated with their
      HDAC inhibition potencies. Treatment of rats with 1 mmol kg(-1) valproic acid for
      two and seven days increased hepatic histone acetylation (1.3- and 3.5-fold,
      respectively) and the expression of mdr1a and mdr2 (2.2-4.1-fold). Valpromide
      (0.5-2.0 mM) did not increase histone acetylation or P-gp expression in rat
      livers, but induced CYP3A expression. CONCLUSIONS: Valproic acid increased P-gp
      expression and function in human tumour cell lines and in rat liver. The clinical
      significance of this increase merits further investigation.

PMID- 16894353
TI  - Androgen-dependent prostate epithelial cell selection by targeting ARR(2)PBneo to
      the LPB-Tag model of prostate cancer.
AB  - Cell cultures representing different stages of prostatic carcinoma will be a
      useful tool allowing a more complete understanding of the role of individual
      genes in tumorigenesis. We used the androgen-regulated probasin promoter linked
      to the neomycin phosphotransferase (Neo) gene, to generate the ARR(2)PBneo
      transgenic mouse model. Development was normal and all six ARR(2)PBneo transgenic
      founder lines expressed the Neo gene in a prostate-specific manner. Line C, which
      expressed high levels of neo, was crossbred to LPB-Tag 12T-7f transgenic mice (in
      which the SV40 large T antigen (Tag) was targeted to the prostate by the large
      probasin (LPB) promoter). Three bigenic males (carrying both Neo and Tag
      transgenes) were identified. Prostatic lesions developed in these mice in a
      predictable and heritable manner, indicating that Neo did not alter Tag-induced
      prostate tumor development and progression. Three separate NeoTag epithelial cell
      strains were established from three bigenic mice. G418 selection was used to
      obtain immortalized epithelial cells in culture. Selected cells expressed the Neo
      and Tag transgenes, cytokeratins 8 and 18, and were androgen responsive for
      growth. To determine if these NeoTag cells maintained a similar in vivo phenotype
      to the 12T-7f transgenic line, tissue recombinations were made with rat
      urogenital sinus mesenchyme (rUGM) and grafted under the renal capsule of male
      nude mouse hosts. In recombinants, the three NeoTag strains developed PIN lesions
      and/or more extensive adenocarcinoma than seen in the 12T-7f mouse. Androgen
      ablation demonstrated that the grafts were androgen responsive. NeoTag cells
      grafted without rUGM developed undifferentiated adenocarcinoma demonstrating that
      prostatic stroma dictates the glandular architecture seen in the well
      differentiated adenocarcinoma.

PMID- 16894354
TI  - Gastrin-induced apoptosis contributes to carcinogenesis in the stomach.
AB  - Hypergastrinemia in INS-GAS mice leads to accelerated carcinogenesis of the
      stomach, but the mechanisms have not been well defined. We investigated the
      possible role of gastrin-induced gastric cell apoptosis in the development of
      gastric cancer. We examined apoptosis and the expression of Bcl-2 family proteins
      in INS-GAS mice of different ages, as well as in gastrin-deficient (GAS-KO) mice
      after gastrin-17 (G-17) infusion. In addition, we studied the effects of the
      gastrin/cholecystokinin-2 (CCK-2) receptor antagonist YF476 and/or histamine H2
      (H-2) receptor antagonist loxtidine on apoptosis and atrophy in INS-GAS mice with
      or without Helicobacter felis (H. felis) infection. INS-GAS mice had age
      associated increases in Bax protein expression and decreases in Bcl-2 protein
      expression, along with increased glandular and epithelial cell apoptosis. At 8
      week gastrin infusions in GAS-KO mice resulted in a similar pattern of altered
      Bax and Bcl-2 expression, followed by gastric cell apoptosis. H. felis infection
      of INS-GAS mice led to increased apoptosis and the development of atrophy,
      whereas treatment with either YF476 and/or loxtidine strongly inhibited both
      apoptosis and atrophy. In vitro studies with Fas-expressing RGM1 cells showed
      that gastrin stimulation alone directly induced apoptosis via gastrin/CCK-2
      receptor and synergized with FasL stimulation. These results indicate that
      gastrin can induce apoptosis in gastric epithelial cells and contribute to the
      development of gastric carcinogenesis.

PMID- 16894355
TI  - Interferon-alpha prevents apoptosis of endothelial cells after short-term
      exposure but induces replicative senescence after continuous stimulation.
AB  - Although the antiangiogenic activity of type I interferons (IFN) is well known,
      the mechanism by which it occurs is unclear. In the present study, we have
      investigated effects of short-term and long-term IFN-alpha exposure on different
      types of endothelial cells (EC). Short-term IFN-alpha treatment resulted in a
      distinct reduction of apoptosis of serum and growth factor starved HUVEC and
      HDMEC. This was accompanied by a strong upregulation of the IFN inducible
      guanylate binding protein-1 (GBP-1) whereas no consistent regulation of several
      known antiapoptotic proteins was evident. Stable transfection of HUVEC with an
      expression vector for GBP-1 mimicked the protective effect of IFN-alpha,
      suggesting that GBP-1 may contribute to the inhibition of apoptosis. When IFN
      alpha, together with serum and EC growth factors, was present continuously a
      decrease of population doublings by more than 40% was observed in both HDMEC and
      HCAEC. In addition, the cells displayed a senescent phenotype significantly
      earlier than control cells and showed an increased adherence for monocytes. Our
      findings suggest that the antiangiogenic effect of IFN-alpha is mediated by
      inducing EC senescence rather than EC apoptosis. Furthermore IFN-alpha released
      in chronic inflammatory conditions might contribute via its prosenescent activity
      to the pathogenesis of atherosclerosis.

PMID- 16894357
TI  - Conditional inactivation of the murine serum response factor in the pancreas
      leads to severe pancreatitis.
AB  - The Serum Response Factor (SRF) is widely expressed transcription factor acting
      at the confluence of multiple signaling pathways and has been implicated in the
      control of differentiation, growth, and cell death. In the present study, we
      found that SRF is expressed in the developing and adult pancreas. To explore the
      possible role of SRF in this organ, we have generated mutant mice with
      conditional disruption of the Srf gene. Such mutants presented normal development
      of both the exocrine and endocrine pancreas indicating that SRF is dispensable
      for pancreas ontogenesis. However, after weaning, these mice developed profound
      morphological alterations of the exocrine pancreas, which were reminiscent of
      severe pancreatitis. In these mice, massive acinar injury, Nuclear Factor Kappa B
      activation and proinflammatory cytokines release led to complete destruction of
      the exocrine pancreas and its replacement by adipose tissue. Despite these
      changes, the organization and function of the endocrine islets of Langerhans
      remained well-preserved. This new animal model of spontaneous pancreatitis could
      prove a valuable tool to gain further insight into the physiopathology of this
      disease.

PMID- 16894356
TI  - Interleukin-3 and c-Kit/stem cell factor are required for normal eosinophil
      responses in mice infected with Strongyloides venezuelensis.
AB  - To evaluate the potential roles of Interleukin-3 (IL-3) and c-Kit, the tyrosine
      kinase receptor for stem cell factor (SCF), in eosinophil responses in vivo, we
      examined eosinophil numbers in uninfected or nematode-infected wild-type mice, IL
      3-/- mice, and IL-3-/- mice that also have a marked reduction in SCF/c-Kit
      signaling (ie, Kit(W)/Kit(W-v), IL-3-/- mice). We found no significant
      differences in the numbers of eosinophils in the blood, bone marrow or various
      tissues of IL-3-/- vs IL-3+/+ mice, either at baseline or after the induction of
      bone marrow, blood or tissue eosinophilia in response to infection with
      Strongyloides venezuelensis (S.v.) or Nippostrongylus brasiliensis (N.b.).
      However, in mice with markedly impaired SCF/c-Kit signaling, IL-3 contributed
      significantly to the increased numbers of eosinophils that were observed in
      multiple tissues during S.v. infection, but not during infection with N.b.

PMID- 16894359
TI  - The role of Toll-like receptors in non-infectious lung injury.
AB  - The role of Toll-like receptors (TLRs) in pathogen recognition has been
      expeditiously advanced in recent years. However, investigations into the function
      of TLRs in non-infectious tissue injury have just begun. Previously, we and
      others have demonstrated that fragmented hyaluronan (HA) accumulates during
      tissue injury. CD44 is required to clear HA during tissue injury, and impaired
      clearance of HA results in unremitting inflammation. Additionally, fragmented HA
      stimulates the expression of inflammatory genes by inflammatory cells at the
      injury site. Recently, we identified that HA fragments require both TLR2 and TLR4
      to stimulate mouse macrophages to produce inflammatory chemokines and cytokines.
      In a non-infectious lung injury model, mice deficient in both TLR2 and TLR4 show
      an impaired transepithelial migration of inflammatory cells, increased tissue
      injury, elevated lung epithelial cell apoptosis, and decreased survival. Lung
      epithelial cell overexpression of high molecular mass HA protected mice against
      acute lung injury and apoptosis, in part through TLR-dependent basal activation
      of NF-kappaB. The exaggerated injury in TLR2 and TLR4 deficient mice appears to
      be due to impaired HA-TLR interactions on epithelial cells. These studies
      identify that host matrix component HA and TLR interactions provide signals that
      initiate inflammatory responses, maintain epithelial cell integrity, and promote
      recovery from acute lung injury.

PMID- 16894358
TI  - Heme: a versatile signaling molecule controlling the activities of diverse
      regulators ranging from transcription factors to MAP kinases.
AB  - Heme (iron protoporphyrin IX) is an essential molecule for numerous living
      organisms. Not only does it serve as a prosthetic group in enzymes, it also acts
      as a signaling molecule that controls diverse molecular and cellular processes
      ranging from signal transduction to protein complex assembly. Deficient heme
      synthesis or function impacts the hematopoietic, hepatic and nervous systems in
      humans. Recent studies have revealed a series of heme-regulated transcription
      factors and signal transducers including Hap1, a heme-activated transcription
      factor that mediates the effects of oxygen on gene transcription in the yeast
      Saccharomyces cerevisiae; Bach1, a transcriptional repressor that is negatively
      regulated by heme in mammalian cells; IRR, an iron regulatory protein that
      mediates the iron-dependant regulation of heme synthesis in the bacterium
      Bradyrhizobium japonicum; and heme-regulated inhibitor, an eucaryotic initiation
      factor 2alpha kinase that coordinates protein synthesis with heme availability in
      reticulocytes. In this review, we summarize the current knowledge about how heme
      controls the activity of these transcriptional regulators and signal transducers,
      and discuss diseases associated with defective heme synthesis, degradation and
      function.

PMID- 16894361
TI  - A simplified approach to analysing bio-electrical impedance data in
      epidemiological surveys.
AB  - BACKGROUND: Bio-electrical impedance analysis (BIA) is widely used to estimate
      body composition. It is simple, quick and cheap, but less accurate than other
      methods. It has potential epidemiological value, but has conventionally required
      validation before application. AIMS: To develop a simple method of expressing
      weight, height and impedance data that avoids the need for population-specific
      validation equations in order to facilitate epidemiological application. METHODS:
      Body composition was measured using the four-component model in young adults (43
      males, 90 females). Impedance (R) was measured hand-foot and foot-foot. Lean mass
      and fat mass were adjusted for height to give lean mass index (LMI) and fat mass
      index (FMI). Based on theoretical principles, we generated the index 1/R, which
      provides an index of body water adjusted for height. Sex-specific regression
      models were used to investigate the relationships between (a) 1/R and LMI, and
      (b) body mass index (BMI) adjusted for 1/R and FMI. The success of this approach
      was evaluated in relation to the conventional BIA approach, using correlation
      analysis. RESULTS: 1/R was a highly significant predictor of LMI. BMI adjusted
      for 1/R was a significant predictor of FMI. Our approach performed as well as the
      conventional approach for LMI, but not for FMI. DISCUSSION: Direct use of BIA
      data, rather than their combination with population-specific equations for the
      prediction of total body water, proved successful at ranking individuals of both
      sexes in terms of LMI and FMI. The index 1/R may prove particularly valuable in
      epidemiological studies where ranking of LMI is required.

PMID- 16894360
TI  - False-positive breath-alcohol test after a ketogenic diet.
AB  - A 59-year-old man undergoing weight loss with very low calorie diets (VLCD)
      attempted to drive a car, which was fitted with an alcohol ignition interlock
      device, but the vehicle failed to start. Because the man was a teetotaller, he
      was surprised and upset by this result. VLCD treatment leads to ketonemia with
      high concentrations of acetone, acetoacetate and beta-hydroxybutyrate in the
      blood. The interlock device determines alcohol (ethanol) in breath by
      electrochemical oxidation, but acetone does not undergo oxidation with this
      detector. However, under certain circumstances acetone is reduced in the body to
      isopropanol by hepatic alcohol dehydrogenase (ADH). The ignition interlock device
      responds to other alcohols (e.g. methanol, n-propanol and isopropanol), which
      therefore explains the false-positive result. This 'side effect' of ketogenic
      diets needs further discussion by authorities when people engaged in safety
      sensitive work (e.g. bus drivers and airline pilots) submit to random breath
      alcohol tests.

PMID- 16894362
TI  - CYP19A1 genetic polymorphisms may be associated with obesity-related phenotypes
      in Chinese women.
AB  - OBJECTIVE: To examine the relationship between genetic polymorphisms of the
      CYP19A1 gene and obesity-related phenotypes, body mass index (BMI) and waist-to
      hip ratio (WHR). SUBJECTS: In total, 1241 Chinese women, who were recruited as
      community controls for a population-based case-control study of breast cancer.
      METHODS: Nineteen haplotype tagging single nucleotide polymorphisms (htSNPs) in
      four haplotype blocks were genotyped. RESULTS: Significant associations were
      observed for WHR at three SNPs that are located in haplotype block 1, including
      rs2445765, rs1004984 and rs1902584 (P=0.05, 0.04 and 0.01, respectively). Women,
      particularly premenopausal women, who carried the minor allele at any of these
      SNPs, had higher WHR than those without it. Of these three SNPs, the strongest
      association was observed at rs1902584, which is the closest to Promoter I.4, the
      major promoter for adipose tissue. Haplotype analyses indicated an association
      between the haplotype TCCAT in block 1 and WHR with a P-value of 0.02.
      CONCLUSION: These results suggested that CYP19A1 genetic polymorphisms may be
      associated with the risk of obesity among Chinese women, especially among
      premenopausal women. The CYP19A1 protein (aromatase) plays a critical role in
      estrogen biosynthesis and thus affects body fat distribution and regulation.

PMID- 16894364
TI  - Guidelines: From artificial evolution to computational evolution: a research
      agenda.
AB  - Computational scientists have developed algorithms inspired by natural evolution
      for at least 50 years. These algorithms solve optimization and design problems by
      building solutions that are 'more fit' relative to desired properties. However,
      the basic assumptions of this approach are outdated. We propose a research
      programme to develop a new field: computational evolution. This approach will
      produce algorithms that are based on current understanding of molecular and
      evolutionary biology and could solve previously unimaginable or intractable
      computational and biological problems.

PMID- 16894365
TI  - Let's return to the "belly bath".

PMID- 16894363
TI  - Linkage analysis of circulating levels of adiponectin in Hispanic children.
AB  - INTRODUCTION: Adiponectin, a hormone produced exclusively by adipose tissue, is
      inversely associated with insulin resistance and proinflammatory conditions. The
      aim of this study was to find quantitative trait loci (QTLs) that affect
      circulating levels of adiponectin in Hispanic children participating in the VIVA
      LA FAMILIA Study by use of a systematic genome scan. METHODS: The present study
      included extended families with at least one overweight child between 4 and 19
      years old. Overweight was defined as body mass index (BMI) 95th percentile.
      Fasting blood was collected from 466 children from 127 families. Adiponectin was
      assayed by radioimmunoassay (RIA) technique in fasting serum. A genome-wide scan
      on circulating levels of adiponectin as a quantitative phenotype was conducted
      using the variance decomposition approach. RESULTS: The highest logarithm of odds
      (LOD) score (4.2) was found on chromosome 11q23.2-11q24.2, and a second
      significant signal (LOD score=3.0) was found on chromosome 8q12.1-8q21.3. In
      addition, a signal suggestive of linkage (LOD score=2.5) was found between
      18q21.3 and 18q22.3. After adjustment for BMI-Z score, the LOD score on
      chromosome 11 remained unchanged, but the signals on chromosomes 8 and 18 dropped
      to 1.6 and 1.7, respectively. Two other signals suggestive of linkage were found
      on chromosome 3 (LOD score=2.1) and 10 (LOD score=2.5). Although the region on
      chromosome 11 has been associated with obesity and diabetes-related traits in
      adult populations, this is the first observation of linkage in this region for
      adiponectin levels. Our suggestive linkages on chromosomes 10 and 3 replicate
      results for adiponectin seen in other populations. The influence of loci on
      chromosomes 18 and 8 on circulating adiponectin seemed to be mediated by BMI in
      the present study. CONCLUSION: Our genome scan in children has identified a novel
      QTL and replicated QTLs in chromosomal regions previously shown to be linked with
      obesity and type 2 diabetes (T2D)-related phenotypes in adults. The genetic
      contribution of loci to adiponectin levels may vary across different populations
      and age groups. The strong linkage signal on chromosome 11 is most likely
      underlain by a gene(s) that may contribute to the high susceptibility of these
      Hispanic children to obesity and T2D.

PMID- 16894366
TI  - The Norton-Simon hypothesis: designing more effective and less toxic
      chemotherapeutic regimens.

PMID- 16894382
TI  - Should patients with ovarian cancer receive intraperitoneal chemotherapy
      following initial cytoreductive surgery?

PMID- 16894383
TI  - Can VEGF-D and VEGFR-3 be used as biomarkers for therapeutic decisions in
      patients with gastric cancer?

PMID- 16894384
TI  - Can high-grade cervical lesions be managed in a single clinic visit?

PMID- 16894385
TI  - Is postmastectomy radiotherapy useful in elderly women with high-risk breast
      cancer?

PMID- 16894386
TI  - Docetaxel plus gemcitabine or docetaxel plus cisplatin in advanced pancreatic
      carcinoma?

PMID- 16894387
TI  - Does prophylactic surgery reduce the risk of gynecologic cancers arising from the
      Lynch syndrome?

PMID- 16894388
TI  - Male breast cancer: a gender issue.
AB  - The incidence of male breast cancer (MBC) is rising; however, mortality due to
      MBC has not changed, unlike female breast cancer. This lack of change is mostly
      attributable to a lack of major progress in the understanding and treatment of
      the disease. The treatment of MBC has been extrapolated from the knowledge of
      female breast cancer, despite the multiple differences in the pathogenesis,
      biology and genetics of these two disease entities, especially the differences
      with regard to the role of male hormones as well as estrogens in MBC compared
      with female disease. Although major advances in hormonal manipulation for the
      treatment of breast cancer are being developed, an improved understanding of the
      potential differences between male and female breast cancer is essential, as this
      would provide new opportunities for therapeutic intervention and probable
      improved outcome for MBC. This review aims at highlighting the major differences
      between male and female breast cancer with an emphasis on hormonal therapy, and
      discusses some of the recent advances in MBC.

PMID- 16894389
TI  - The management of tumor lysis syndrome.
AB  - The manifestation of tumor lysis syndrome (TLS) occurs when the destruction of
      tumor cells releases breakdown products that overwhelm the excretory mechanisms
      of the body. A cardinal sign is hyperuricemia, leading to uric acid nephropathy.
      Other signs are hyperkalemia, hyperphosphatemia and secondary hypocalcemia.
      Conventional management of TLS consists of aggressive intravenous hydration,
      diuretic therapy, urinary alkalization, and inhibition of urate production by
      high-dose allopurinol. Urate oxidase has been used in the management of patients
      at risk for TLS and recently the recombinant urate oxidase rasburicase was
      developed. Several data indicate that rasburicase is effective and well tolerated
      in the prevention and treatment of chemotherapy-induced hyperuricemia. Treatment
      options of hyperkalemia include sodium polystyrene sulfonate, hypertonic glucose
      and insulin, loop diuretics, and bicarbonate. Treatment of hyperphosphatemia
      reduces dietary phosphate intake and includes phosphate binders such as aluminum
      hydroxide and aluminum carbonate. When recurrent hypocalcemia is present, a
      continuous intravenous infusion of calcium gluconate can be initiated.
      Hemodialysis should be considered for every patient with excessively elevated
      uric acid, phosphate and/or potassium and in those patients with acute renal
      failure to control urinary volume and manage uremia.

PMID- 16894390
TI  - Mechanisms of disease: Oncogene addiction--a rationale for molecular targeting in
      cancer therapy.
AB  - There has been considerable progress in the systemic treatment of cancer because
      of the rapid development and clinical application of molecular targeted agents.
      Although patients with a particular type and stage of cancer are often treated as
      a single group, more-specific therapy is being considered, as subsets of these
      patients who are more likely to benefit from treatment with particular agents are
      being identified. We previously introduced the concept of 'oncogene addiction' to
      explain how some cancers that contain multiple genetic, epigenetic, and
      chromosomal abnormalities are dependent on or 'addicted' to one or a few genes
      for both maintenance of the malignant phenotype and cell survival. Thus, reversal
      of only one or a few of these abnormalities can inhibit cancer cell growth and in
      some cases translate to improved survival rates. This review summarizes current
      experimental and clinical evidence for the concept of oncogene addiction and
      describes molecular mechanisms that may explain this phenomenon. In addition, we
      discuss how high-throughput screening methods, including gene-expression
      profiling and proteomics, and emerging methods for analyzing complex cellular
      networks can be used to identify the state of oncogene addiction, i.e. the
      'Achilles' heel,' in specific cancers. Finally, we discuss the use of molecular
      targeted agents in combination with other anticancer agents as a strategy to
      optimize therapy and prevent disease recurrence.

PMID- 16894391
TI  - Metastatic spinal cord compression: the hidden danger.
AB  - BACKGROUND: A 47-year-old male underwent resection of a left-shoulder melanoma in
      1997. In November 2004 he was found to have multiple brain lesions and adrenal,
      lung, and bone metastases, and in January 2005 underwent resection of his
      symptomatic right parietal lobe lesion and subsequent whole-brain radiation. In
      February 2005 he experienced headaches and word-finding difficulty and was found
      to have four progressive brain lesions on MRI. These were resistant to
      conventional radiotherapy and were treated with stereotactic radiosurgery. The
      patient later developed an obstruction of the jejunum and underwent resection of
      multiple abdominal masses. In April 2005, the patient commenced temozolomide and
      underwent radiation therapy to the left arm for pain thought to be caused by an
      increase in size of his melanoma metastasis. In August 2005 the patient reported
      persistent and worsening arm pain, despite a further course of radiotherapy in
      June 2005. INVESTIGATIONS: Physical examination including a thorough neurological
      examination, radiography, X-ray, CT scan, and MRI. DIAGNOSIS: Metastatic melanoma
      to the cervical spine (C7 vertebra) with spinal cord compression. MANAGEMENT:
      Involved field radiotherapy, temozolomide, opioids, gabapentin, corticosteroids,
      and Cyberknife therapy.

PMID- 16894392
TI  - The etiology of poststroke depression: a review of the literature and a new
      hypothesis involving inflammatory cytokines.
AB  - Although poststroke depression is unlikely to represent a single disorder and
      numerous etiologies for different kinds of poststroke depression will likely
      emerge as the result of future research, we believe that a number of poststroke
      depressive disorders are likely to be the result of specific changes in brain
      pathology and neurophysiology. Nevertheless, there are relatively few hypotheses
      about the pathophysiology of poststroke depression. This paper, therefore,
      proposes a new hypothesis for poststroke depression involving increased
      production of proinflammatory cytokines resulting from brain ischemia in cerebral
      areas linked to the pathogenesis of mood disorders. This paper reviews the
      evidence supporting the hypothesis that proinflammatory cytokines are involved in
      the occurrence of stroke as well as mood disorders linked to the brain damage.
      The increased production of proinflammatory cytokines such as IL-1beta, TNF-alpha
      or IL-18 resulting from stroke may lead to an amplification of the inflammatory
      process, particularly in limbic areas, and widespread activation of indoleamine
      2,3-dioxygenase (IDO) and subsequently to depletion of serotonin in paralimbic
      regions such as the ventral lateral frontal cortex, polar temporal cortex and
      basal ganglia. The resultant physiological dysfunction may lead to poststroke
      depression. Future investigations may explore this hypothesis through more
      extensive studies on the role of proinflammatory cytokines, such as IL-1beta, TNF
      alpha or even IL-18, in patients with poststroke depression.

PMID- 16894393
TI  - Genetic and clinical analysis of a large Dutch Gilles de la Tourette family.
AB  - Gilles de la Tourette syndrome is a complex neuropsychiatric disorder, which
      becomes evident in childhood between the ages of 2 and 15 years. Tourette
      syndrome is defined by the occurrence of a large range and variable number of
      unwanted repetitive simple or complex motor and vocal tics that start in
      childhood and follow a waxing and waning course. A major gene for this syndrome
      has not yet been identified, probably owing to both genetic and phenotypic
      heterogeneity of this disease. This article describes the clinical evaluation of
      patients and family members in a large Dutch Gilles de la Tourette Syndrome
      pedigree and the decisions encountered with respect to phenotyping. The
      importance of an accurate definition of the Tourette phenotype is discussed,
      which is highly important for reliable genetic linkage and association studies.
      Subsequent linkage analysis resulted in three linkage peaks on different
      chromosomes 3q, 9q, and 13q. Multipoint analysis resulted in a single linkage
      peak with logarithm of odds score 2.55 with marker D3S1311 on chromosome 3q.

PMID- 16894394
TI  - Gene expression analysis of bipolar disorder reveals downregulation of the
      ubiquitin cycle and alterations in synaptic genes.
AB  - Bipolar affective disorder is a severe psychiatric disorder with a strong genetic
      component but unknown pathophysiology. We used microarray technology to determine
      the expression of approximately 22,000 mRNA transcripts in post-mortem tissue
      from two brain regions in patients with bipolar disorder and matched healthy
      controls. Dorsolateral prefrontal cortex tissue from a cohort of 70 subjects and
      orbitofrontal cortex tissue from a separate cohort of 30 subjects was
      investigated. The final analysis included 30 bipolar and 31 control subjects for
      the dorsolateral prefrontal cortex and 10 bipolar and 11 control subjects for the
      orbitofrontal cortex. Differences between disease and control groups were
      identified using a rigorous statistical analysis with correction for confounding
      variables and multiple testing. In the orbitofrontal cortex, 393 differentially
      expressed transcripts were identified by microarray analysis and a representative
      subset was validated by quantitative real-time PCR. Pathway analysis revealed
      significant upregulation of genes involved in G-protein coupled receptor
      signalling and response to stimulus (in particular the immune response), while
      genes relating to the ubiquitin cycle and intracellular transport showed
      coordinated downregulation in bipolar disorder. Additionally, several genes
      involved in synaptic function were significantly downregulated in bipolar
      disorder. No significant changes in gene expression were observed in the
      dorsolateral prefrontal cortex using microarray analysis or quantitative real
      time PCR. Our findings implicate the orbitofrontal cortex as a region prominently
      involved in bipolar disorder and indicate that diverse processes are affected.
      Overall, our results suggest that dysregulation of the ubiquitin pathway and
      synaptic function may be central to the disease process.

PMID- 16894396
TI  - Antecedents of emotion knowledge: Predictors of individual differences in young
      children.
AB  - Individual differences in emotion knowledge were examined among 188 4-year-old,
      predominantly African American children. Cognitive ability and negative
      emotionality, maternal characteristics (parenting, verbal intelligence, and
      depressive symptoms), environmental risk, and child sex were examined as
      predictors of emotion knowledge. Regression analyses indicated that cognitively
      skilled children who resided in relatively low risk environments with verbally
      intelligent mothers possessed greater emotion knowledge. Proximal (4-year) child
      cognitive ability was a stronger predictor than distal (2-year) cognitive
      ability. Positive parenting at 4 years was correlated with child emotion
      knowledge, but this relation disappeared when parenting was examined in the
      context of other predictors. These findings highlight the potential role of child
      cognitive ability, along with environmental risk and maternal verbal
      intelligence, in children's emotion knowledge and demonstrate the importance of
      examining a variety of predictors for their unique contribution to emotion
      knowledge.

PMID- 16894397
TI  - Vibrational Dynamics of Biological Molecules: Multi-quantum Contributions.
AB  - High-resolution X-ray measurements near a nuclear resonance reveal the complete
      vibrational spectrum of the probe nucleus. Because of this, nuclear resonance
      vibrational spectroscopy (NRVS) is a uniquely quantitative probe of the
      vibrational dynamics of reactive iron sites in proteins and other complex
      molecules. Our measurements of vibrational fundamentals have revealed both
      frequencies and amplitudes of (57)Fe vibrations in proteins and model compounds.
      Information on the direction of Fe motion has also been obtained from
      measurements on oriented single crystals, and provides an essential test of
      normal mode predictions. Here, we report the observation of weaker two-quantum
      vibrational excitations (overtones and combinations) for compounds that mimic the
      active site of heme proteins. The predicted intensities depend strongly on the
      direction of Fe motion. We compare the observed features with predictions based
      on the observed fundamentals, using information on the direction of Fe motion
      obtained either from DFT predictions or from single crystal measurements. Two
      quantum excitations may become a useful tool to identify the directions of the Fe
      oscillations when single crystals are not available.

PMID- 16894398
TI  - Tacrolimus: focusing on atopic dermatitis.
AB  - Tacrolimus ointment is an effective treatment for atopic dermatitis. As a
      calcineurin inhibitor, it works through the FK-binding protein, inhibiting
      calcineurin and preventing dephosphorylation of nuclear factor of activated T
      cells (NFAT). Systemic absorption from the drug is minimal, allowing a favorable
      safety profile. In head-to-head clinical trials with pimecrolimus, tacrolimus
      proved to be a more effective treatment. Tacrolimus ointment has also been
      compared to standard topical cortico-steroid treatments and is equally effective
      if not superior to several topical steroids. Overall, tacrolimus ointment is a
      safe and effective treatment for atopic dermatitis and can be used as an
      adjunctive treatment to standard management with topical corticosteroids.

PMID- 16894395
TI  - The analysis of 51 genes in DSM-IV combined type attention deficit hyperactivity
      disorder: association signals in DRD4, DAT1 and 16 other genes.
AB  - Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental
      disorder, starting in early childhood and persisting into adulthood in the
      majority of cases. Family and twin studies have demonstrated the importance of
      genetic factors and candidate gene association studies have identified several
      loci that exert small but significant effects on ADHD. To provide further
      clarification of reported associations and identify novel associated genes, we
      examined 1,038 single-nucleotide polymorphisms (SNPs) spanning 51 candidate genes
      involved in the regulation of neurotransmitter pathways, particularly dopamine,
      norepinephrine and serotonin pathways, in addition to circadian rhythm genes.
      Analysis used within family tests of association in a sample of 776 DSM-IV ADHD
      combined type cases ascertained for the International Multi-centre ADHD Gene
      project. We found nominal significance with one or more SNPs in 18 genes,
      including the two most replicated findings in the literature: DRD4 and DAT1. Gene
      wide tests, adjusted for the number of SNPs analysed in each gene, identified
      associations with TPH2, ARRB2, SYP, DAT1, ADRB2, HES1, MAOA and PNMT. Further
      studies will be needed to confirm or refute the observed associations and their
      generalisability to other samples.

PMID- 16894399
TI  - Lapatinib: a novel EGFR/HER2 tyrosine kinase inhibitor for cancer.
AB  - Lapatinib is an oral dual tyrosine kinase inhibitor that targets epidermal growth
      factor receptor (EGFR) and human epidermal growth factor receptor-2 (HER2), both
      frequently overexpressed in human cancer. Preclinical data have shown that
      lapatinib is a potent and selective inhibitor of the tyrosine kinase domain of
      EGFR and HER2, and tumor cells that overexpress these receptors are growth
      inhibited by lapatinib both in vitro and in vivo. Phase I clinical trials have
      shown that lapatinib is well tolerated, with mild diarrhea and rash the most
      frequent toxicities, and early evidence of clinical efficacy has been reported
      especially in HER2-positive breast cancer. Phase II studies have shown activity
      for lapatinib in trastuzumab-refractory breast cancer either alone or in
      combination with trastuzumab. When used as first-line monotherapy for advanced
      breast cancer, objective tumor responses have been seen in 28% of patients with
      untreated HER2-positive advanced breast cancer. An extensive phase III program in
      advanced breast cancer is now in progress both for refractory disease and as
      first-line therapy in combination with chemotherapy with and without trastuzumab,
      and with endocrine therapy. Phase II studies have also been conducted in a
      variety of other tumors, including renal cell cancer. Parallel biomarker studies
      are starting to elucidate predictive molecular phenotypes that may indicate
      likelihood of response to lapatinib, and these may direct future trials with this
      oral tyrosine kinase inhibitor.

PMID- 16894400
TI  - Nelarabine use in leukemias.
AB  - Drug discovery and development over the past 60 years has played a central role
      in the continuous improvement in survival rates of patients undergoing treatment
      for acute lymphoblastic leukemia. It has recently been suggested that in children
      and adolescents diagnosed with acute lymphoblastic leukemia, an overall cure rate
      of 90% may be achieved (1, 2). Cure rates in adults, typically less than 40%, are
      considerably lower than in the younger populations, even in the face of currently
      prescribed optimal drug therapy and supportive care (3-5). The search for more
      effective and safer anti-leukemia therapy continues to identify agents and
      combinations of agents that have activity against specific types of acute
      lymphoblastic leukemia (1). This review presents a new compound, nelarabine, that
      has shown efficacy in treating patients with T-cell acute lymphoblastic leukemia
      or T-cell lymphoblastic lymphoma.

PMID- 16894401
TI  - Aspirin for the primary prevention of cardiovascular events.
AB  - There is significant evidence that low-dose aspirin is effective in preventing
      the first myocardial infarction in men and ischemic stroke in women. There is
      also an increased risk for major gastrointestinal tract hemorrhage and a
      suggestive, but nonsignificant, increase in the risk for hemorrhagic stroke. If
      there is a history of ulcer disease or upper-gastrointestinal tract bleeding,
      Helicobacter pylori should be eradicated (if present) and a proton pump inhibitor
      used with aspirin therapy. In conclusion, the benefits of low-dose aspirin (75
      162 mg/day) in the prevention of myocardial infarction in men and thrombotic
      stroke in women generally outweigh the risks of serious bleeding in adults with a
      coronary heart disease risk >1% per year or >1% in 10 years.

PMID- 16894402
TI  - Links between Alzheimer's disease and diabetes.
AB  - The existence of links between Alzheimer's disease and diabetes is an important
      topic currently under active debate. Establishing such links if they exist and
      defining their common pathogenesis and pathophysiological mechanisms may lead to
      new concepts and research directions for the pharmacological treatment of
      Alzheimer's disease and diabetes. Alzheimer's disease is associated with
      peripheral and central insulin abnormalities. Cognitive capacities are often
      impaired in patients with diabetes. There are many mechanisms by which insulin
      signaling abnormalities may affect clinical and pathological outcome of
      Alzheimer's disease. Insulin resistance and dysregulation of the degradation of
      neurotoxic amyloid and insulin appear at the core of the links between
      Alzheimer's disease and diabetes. Functions and expression of insulysin, an
      enzyme involved in the degradation of neurotoxic amyloid peptides and insulin,
      are usually impaired or reduced in Alzheimer's disease and diabetes. The
      increased occurrence of insulin resistance in Alzheimer's disease suggests that
      improving insulin effectiveness and insulysin activity may have therapeutic value
      in Alzheimer's disease patients and therefore is worth intensive investigation.

PMID- 16894403
TI  - Antitumor efficiency of novel fluoro-substituted 6-amino-2-phenylbenzothiazole
      hydrochloride salts in vitro and in vivo.
AB  - The purpose of this study was to investigate antitumor activity of novel fluoro
      substituted 6-amino-2-phenylbenzothiazole hydrochloride salts in vitro and in
      vivo. A novel series of hydrochloride or dihydrochloride salts of the novel 2
      (fluoro-substituted phenyl)-6-aminobenzothiazoles (5-7) have been prepared in
      multistep synthesis starting from 3- or 4-fluorobenzaldehydes and 2-amino-5
      nitrothiophenol and evaluated for their antiproliferative activity against human
      cervical (HeLa), breast (MCF-7), colon (CaCO-2), and laryngeal (Hep-2) carcinomas
      and against fibroblast cell lines (WI-38). Also, antitumor activity of these
      compounds was evaluated in vitro and in vivo against murine melanoma (B16-F10),
      fibrosarcoma (FsaR), and squamous cell carcinoma (SCCVII). The tested compounds
      were found to exert good cytotoxic activity in vitro. The cytotoxic effect was
      selective, cell specific, and dose dependent, between 33 microM for MCF-7 and 110
      microM for WI-38. Benzothiazoles reduced de novo protein and DNA synthesis up to
      75%. All examined benzothiazoles had significant antitumor activity in vivo
      against melanoma B16-F10, fibrosarcoma, and squamous cell carcinoma. The best
      therapeutic results were achieved when therapy started 7 days after tumor cell
      implantation and when benzothiazoles were given repeatedly five times every 2
      days, i.e., on day 7, 9, 11, 13, and 15 after transplantation of tumor cells.

PMID- 16894404
TI  - Human erythrocytes are not suitable for determination of intravascular volume of
      perfused rat liver.
AB  - Homologous or heterologous erythrocytes have been widely used for the estimation
      of intravascular volume of the liver. However, cross-species blood mediates
      immune response in the organ, and foreign cells are rapidly cleared from the
      plasma, indicating that heterologous erythrocytes may not be a suitable marker
      for determination of vascular space. This aspect was investigated in the perfused
      rat liver preparation following bolus administration of human (heterologous)
      erythrocytes into the portal vein. To compare the extent of its distribution
      within the liver, rat (homologous) erythrocytes and Evans blue were chosen as the
      reference vascular and extracellular markers, respectively. Hepatic distribution
      of human erythrocytes was influenced by the perfusion medium (with and without
      protein) and injection number (first and second injections). Mean transit time
      and hence volume of distribution decreased in the presence of protein and
      repetition of the injection. Even in the presence of protein, the volume of
      distribution obtained for human erythrocytes was larger than that of the
      extracellular volume of the liver obtained with Evans blue (0.22 +/- 0.01 vs.
      0.20 +/- 0.02 ml/g), indicating that they are not suitable for determination of
      intravascular volume of the perfused rat liver preparation.

PMID- 16894405
TI  - Effects of bisphosphonates on prostaglandin E2 and thromboxane B2 production in
      human whole blood and monocytes stimulated by lipopolysaccharide and A23187.
AB  - Bisphosphonates are antiatherosclerotic, suppress monocyte-macrophages, and
      modulate proinflammatory mediators. Prostaglandin (PG) E(2), thromboxane (TX)
      A(2), and cyclooxygenase-2 (COX-2) enzyme are involved in inflammation and
      atherosclerosis. We studied the effects of four bisphosphonates (etidronate,
      clodronate, tiludronate, and alendronate) on PGE(2) and TXB(2) production in
      human whole blood and monocytes. PGE(2) and TXB(2) were determined by direct
      radioimmunoassay and COX-2 expression by Western blot. In whole blood, the
      bisphosphonates did not modulate the increase in PGE(2) and TXB(2) concentrations
      induced by calcium ionophore A23187 or lipopolysaccharide (LPS). None of the
      bisphosphonates did change PGE(2) and TXB(2) concentration after spontaneous
      clotting. A23187- and spontaneous clotting-induced PGE(2) and TXB(2) productions
      were inhibited over 90% by acetylsalicylic acid (ASA), and LPS-induced PGE(2) and
      TXB(2) formations were inhibited over 90% by nimesulide. None of the
      bisphosphonates altered these inhibitions. In monocytes, etidronate and
      clodronate augmented A23187-stimulated PGE(2) production 2.5- to 3.2-fold (p <
      0.05). LPS- or A2318-induced elevations in TXB(2) were not influenced by the
      bisphosphonates. The tested bisphosphonates neither induced COX-2 expression nor
      modulated LPS-induced COX-2 expression in monocytes. The results suggest that the
      antiatherosclerotic effects of bisphosphonates are not mediated via PGE(2),
      TXA(2), or COX-2, and the bisphosphonates do not interfere with the suppression
      of platelet COX-1 activity by ASA and COX-2 activity by nimesulide.

PMID- 16894407
TI  - Comparative bioavailability between two Tramadol once-daily oral formulations.
AB  - The aim of this study was to compare the pharmacokinetic profile and oral
      bioavailability of Tramadol Contramid once-daily (o.d.) 200 mg tablets
      (Labopharm, Canada) with that of Zytram 200 mg tablets (Zambon, Spain), following
      single-dose administration in 26 healthy volunteers. The study had an open,
      randomized, crossover design with a 7-day wash-out. Data from 24 subjects were
      used for the pharmacokinetic (PK) analysis. Racemic tramadol and racemic O
      demethyltramadol (M1) were assayed in plasma using a liquid chromatography/tandem
      mass spectrometry method. Primary PK parameters estimated were AUC(0-t), AUC(0
      infinity), C(max), C(24 h), and T(max). Results were compared using an ANOVA, and
      the residual variability thereby obtained was used to construct the classical 90%
      confidence intervals. The parametric Schuirmann's test was also performed. T(max)
      was analyzed by a nonparametric approach. For both racemic tramadol and racemic O
      demethyltramadol, the ANOVA showed a statistically significant formulation
      effect. Significantly higher values were obtained for Tramadol Contramid o.d. for
      all PK parameters, except for T(1/2). For Tramadol Contramid o.d., mean tramadol
      plasma levels were maintained at a plateau level above 200 ng/ml from 4 to 16 h
      after dose, while for the reference formulation, that level was sustained from 4
      to only 6 h. Consistent results for both formulations were obtained for the
      metabolite. At the end of the dosing interval, plasma tramadol and O
      demethyltramadol concentrations were 39% and 49% higher, respectively, for
      Tramadol Contramid o.d. than those for Zytram (p < 0.0001). Tramadol Contramid
      o.d. could be considered suprabioavailable to Zytram o.d.

PMID- 16894408
TI  - Gateways to clinical trials.
AB  - Gateways to Clinical Trials are a guide to the most recent clinical trials in
      current literature and congresses. The data in the following tables have been
      retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the
      drug discovery and development portal, http://integrity.prous.com. This issue
      focuses on the following selection of drugs:(R)-Flurbiprofen, 90Yttrium-DOTA
      huJ591; ABT-510, ACP-103, Ad5-FGF4, adalimumab, ademetionine, AG-7352,
      alemtuzumab, Amb a 1 ISS-DNA, anakinra, apaziquone, aprepitant, aripiprazole,
      atazanavir sulfate; BAL-8557, bevacizumab, BMS-188797, bortezomib, bosentan,
      brivudine; Calcipotriol/betamethasone dipropionate, cannabidiol, caspofungin
      acetate, catumaxomab, CERE-120, cetuximab, ciclesonide, cilomilast, cizolirtine
      citrate, Cypher, cystemustine; Dalbavancin, darifenacin hydrobromide, dasatinib,
      deferasirox, denosumab, desmoteplase, dihydrexidine, dimethyl fumarate,
      dutasteride, DW-166HC; Eculizumab, enfuvirtide, entecavir, epratuzumab, erlotinib
      hydrochloride, escitalopram oxalate, eszopiclone, etoricoxib, everolimus;
      Fallypride, febuxostat, fenretinide, fesoterodine, fingolimod hydrochloride;
      Gabapentin enacarbil, gefitinib; hMaxi-K, human papillomavirus vaccine, HYAL
      CT1101; Imatinib mesylate, indiplon, inolimomab, ISAtx-247; J591; Lacosamide,
      landiolol, lasofoxifene tartrate, lestaurtinib, lidocaine/prilocaine, linezolid,
      lixivaptan, lonafarnib, lopinavir, lopinavir/ritonavir, lumiracoxib; Natalizumab,
      nesiritide; OC-108, omalizumab, onercept, OSC; Palifermin, palonosetron
      hydrochloride, parathyroid hormone (human recombinant), parecoxib sodium, PD-MAGE
      3 vaccine, PEG-filgrastim, peginterferon alfa-2a, peginterferon alfa-2b,
      pegsunercept, pelitinib, pitavastatin calcium, plerixafor hydrochloride,
      posaconazole, prasterone sulfate, pregabalin; Ramelteon, ranelic acid distrontium
      salt, rasburicase, rosuvastatin calcium, rotigotine, RSD-1235, rufinamide,
      rupatadine fumarate; Sarizotan hydrochloride, SHL-749, sirolimus-eluting stent,
      solifenacin succinate, sunitinib malate; Tadalafil, talampanel, tasidotin
      hydrochloride, Taxus, tegaserod maleate, telavancin hydrochloride, tenofovir
      disoproxil fumarate, tiotropium bromide, tocilizumab, tositumomab, treprostinil
      sodium, tridolgosir hydrochloride, TTS-CD3; Ularitide; Valdecoxib, Val-Tyr
      sardine peptidase, vardenafil hydrochloride hydrate, voriconazole; Yttrium (90Y)
      edotreotide, Yttrium 90 (90Y) ibritumomab tiuxetan; Zileuton, zucapsaicin.

PMID- 16894406
TI  - Effects of coffees before and after special treatment procedure on cell membrane
      potentials in stomach cells.
AB  - Coffee, one of the most excessively used beverages worldwide, commences the risk
      of gastroesophageal reflux (GER), which may lead to gastric ulcers and increase
      the risk of gastric cancer. Many attempts have been made by the coffee industry
      to diminish the irritating effect on mucosa by means of altering the extraction
      methods concerning gerbic acids and the roasting processes. This paper describes
      the effect of differently produced coffees involving two brands of Darboven and
      two brands of other coffee roasters. The aim of this study was to prove the
      results of gastric potential measurements we found in literature by using human
      AGS gastric epithelial cells (human adenocarcinoma). All four coffee extracts
      tested differentially affected the membrane resting potential of AGS cells.
      Coffees no. 1 and no. 2 depolarized the cells, presumably by increasing the
      cation entry into the cytosol. In marked contrast, coffee no. 4 hyperpolarizes
      the cells, possibly by H(+) extrusion and/or Cl(-) influx, suggesting that this
      coffee might increase acidity in the stomach, which might negatively affect the
      stomach, especially in people with gastroesophageal reflux symptoms. Overall, our
      data suggest that different roasting methods of coffees affect the membrane
      potentials of AGS stomach cells, resulting in increased influx of H+ possibly
      resulting in decreased stomach acidity and thus reducing GER. These results are
      in good accordance with clinical pharmacological results from potential
      difference measurements in healthy volunteers we found in the literature.

PMID- 16894409
TI  - The physician should benefit, not harm the patient.
AB  - Six hundred years before Christ, Hippocrates said that physicians on exercising
      their medical duties, should benefit but not harm their patients. Seventy years
      ago increased medical radiation caused radiologists in the US an excess risk of
      leukemia, lymphoma and multiple myeloma. Now medical radiation is rather safe for
      the physician but the question remains if proper prophylactic measures are being
      taken to make it safe for the subjects examined. Roughly, first trimester of
      pregnancy radiography has a much greater fatal cancer risk than that of exposures
      taken later in pregnancy. It is suggested that women should be administered the
      minimum activity consistent with achieving the desired clinical information,
      whether or not they are known to be pregnant. The best available risk estimates
      suggest that pediatric CT diagnostic procedures will induce significantly
      increased lifetime radiation risk in children. Professor Roger Clarke wrote that
      there may be a need to reduce or prevent doses of medical radiation up to 3 mSv
      if there is no benefit to the individual. 30 mSv is described as "a dose which
      should not be exceeded" and can be approached only if there is a benefit to
      individuals and the dose is difficult to reduce or prevent. In WHO Category III
      a) Static brain imaging with technetium-99m pertechnetate, b) Gated cardiac
      imaging c) Bone imaging with technetium-99m MDP, c) Quantitative haemodynamics
      with technetium-99m pertechnetate, d) myocardial imaging with thallous-201
      chloride and e) abscess imaging with gallium-67 citrate, induce an effective dose
      equivalent of 5-9 mSv. A CT scan commonly gives 25 mSv to the subject examined.
      BEIR VI indicated that a 10 mSv single population dose is associated with a
      lifetime attributable risk for developing a solid cancer or leukemia in 1:1000.
      Multiple CT examinations have administered to some patients with renal colic a
      dose of 19.5-153.7 mSv. One may suggest that there should be "justification" and
      informed written patients' consent for nuclear medicine examinations
      administering to the patient doses greater than 5 mSv, especially doses around or
      above 30 mSv / year.

PMID- 16894410
TI  - Scintigraphic imaging of experimental colitis with technetium-99m-infliximab in
      the rat.
AB  - The radiolabeled monoclonal antibody (99m)Tc-infliximab was assessed as an
      inflammation imaging agent in a rat colitis model in comparison with (99m)Tc-tin
      colloid-labeled-leucocytes. (99m)Tc-infliximab and (99m)Tc-tin fluoride colloid
      labeled-leucocytes were administered to (n>3) rats previously exposed to 2,4,6
      trinitrobenzenesulfonic acid by rectal instillation. Whole body scintigraphic
      images were acquired and physiological organ assays were performed to obtain
      quantitative data. Histological examination of colon samples was performed to
      assess the site and severity of the colitis. In the inflamed colon, (99m)Tc
      infliximab resulted in inflamed target (T) to control (C) colon tracer uptake
      ratios of 2.7 +/- 1.0 (n=5) and 2.6 +/- 0.3 (n=5) at 1 and 4 h post tracer
      injection respectively. (99m)Tc-leucocytes gave higher ratios of 19.5 +/- 9.9
      (n=3) and 41.2 +/- 16.1 (n=5) respectively. (99m)Tc-leucocytes gave higher ratios
      of 19.5 +/- 9.9 and 41.2 +/- 16.1 at the corresponding time points. (99m)Tc
      infliximab accumulated at sites of inflammation in this rat model but not due to
      a specific tumor necrosis factor-alpha binding mechanism. Although the tracer
      uptake was lower than radioactive leucocytes, this easily prepared (99m)Tc
      monoclonal antibody may have some advantages in imaging inflammatory bowel
      disease in humans based on its biological activity.

PMID- 16894411
TI  - Evaluation of the left ventricular hemodynamic function and myocardial perfusion
      by gated single photon emission tomography, in patients with type 1 diabetes
      mellitus; prodromal signs of cardiovascular disease after four years.
AB  - The aim of this study was to assess the changes in hemodynamic function and
      myocardial perfusion of the left ventricle occurring in patients with type 1
      diabetes mellitus (DM1) 47-49 months after the first assessment. We have studied
      20 asymptomatic patients, five females and 15 males, aged 22-46 y. The patients
      were under intensive insulin treatment and had normal electrocardiogram (ECG) at
      rest. In all patients gated single photon emission tomography (GSPET) was
      performed at rest and after exercise (examination I). After 47-49 months this
      test was repeated (examination II). GSPET was performed 60 min after the
      intravenous injection of 740 MBq of technetium-99m 2-methoxy-isobutyl-isonitrile
      ((99m)Tc-MIBI), using a dual-headed gamma-camera. Left ventricular ejection
      fraction (LVEF), end diastolic volume (EDV) and end systolic volume (ESV) were
      calculated using quantitative GSPET (QGS). The intensity of perfusion defects was
      also evaluated based on a four degree QGS scale. Our results were as follows: a)
      In examination I, performed at rest: LVEF was 56.1%+/-7.5%, EDV 96.9+/-25.8 ml
      and ESV 42.6+/-16.3 ml. b) In examination I at stress: LVEF was 57.2%+/-7.5%, EDV
      94.1+/-24.0 ml and ESV 40.5+/-15.5. c) In examination II performed at rest: LVEF
      was 58.1%+/-6.5%, EDV 112.1+/-26.1 ml and ESV 46.6+/-14.9 ml and d) In
      examination II at stress: LVEF 57.8%+/-5.6%, EDV 107.9+/-27.4 ml and ESV 44.9+/
      14.4 ml. Significant differences were found between examinations I and II,
      regarding: a) EDV at rest (P<0.001) and at stress (P<0.001) and b) ESV at rest
      (P<0.05) and at stress (P<0.005). Correlation analysis revealed significant
      correlation between LVEF at rest and at stress both in examination I (r=0.83;
      P<0.001) and also in examination II (r=-0.897; P<0.001). Intensity of myocardial
      perfusion defects in examination I at rest and at stress was: 1.68+/-0.5 and
      2.2+/-0.6 degrees respectively. Intensity of myocardial perfusion defects in
      examination II at rest and at stress was: 1.75+/-0.4 and 2.2+/-0.5 respectively.
      No significant differences in the intensity of these perfusion defects were
      found. EDV both at rest and at stress was significantly higher in examination II
      as compared with the examination I study. Similar, but less pronounced changes of
      ESV were found. This study confirms other authors' observations on LV, EDV and
      LV, ESV and also that the percentage of asymptomatic DM1 patients having silent
      myocardial ischemia is high as was in all our patients. Nevertheless, in the
      current literature, we were unable to find a study similar to the present one,
      comparing basal and after four years LV functional GSPET data, in asymptomatic
      DM1 patients. In conclusion, myocardial perfusion GSPET was useful as a screening
      test in DM1 patients in showing four years after the basal study, prodromal signs
      of cardiovascular disease, especially increase of left ventricular volumes and
      silent myocardial ischemia, in these patients. Our research on the above protocol
      is being continued.

PMID- 16894412
TI  - Comparison of left ventricular functional parameters measured by gated single
      photon emission tomography and by two-dimensional echocardiography.
AB  - The aim of the present study was to evaluate the correlation amongst left
      ventricular (LV) functional parameters estimated by gated single photon emission
      tomography (GSPET) and two-dimensional (2D) M-mode, echocardiography (ECHOC).
      GSPET was performed in a single day stress/rest protocol by using either
      technetium-99m methoxy-isobutyl-isonitrile ((99m)Tc-MIBI) or technetium-99m
      tetrofosmin ((99m)Tc-myoview) in 36 consecutive patients, 21 males and 15
      females; mean age 57.6+/-11.8 y, range 32-82 y. The various LV parameters studied
      were: ejection fraction (EF), end systolic volume (ESV), end diastolic volume
      (EDV), stroke volume (SV) and LV mass (LVM). The GSPET data were reconstructed
      using an automatic algorithm employing filtered back projection (FBP) and further
      analyzed by Emory cardiac (EC) toolbox versions EO-00369 and EO-00733 for the
      quantitative determinations of these parameters. All patients underwent ECHOC
      within 1-2 h of the post-stress data acquisition of GSPET. Our results showed
      that the LV volumes and the LVM showed good correlation (r=0.749 to 0.952,
      P=0.01). These values could thus be used interchangeably. The assessment of these
      parameters by GSPET therefore does not seem to be affected by the dose of the
      radioactivity administered as the dose of the (99m)Tc-labeled myocardial agents
      for acquiring rest study was approximately four times higher than that for the
      stress study. Our results also showed that the mean +/- SD values of the volumes
      and the EF of the LV evaluated by the two techniques, differed significantly
      except significant correlations for ESV, EDV and LVEF were observed between the
      two methods: r=0.574 to 0.954; 0.347 to 0.952 and 0.516 to 0.876 respectively. On
      the other hand, a wide disagreement was observed in estimating the LVM by the two
      techniques. The LVM measurements by 2D ECHOC were approximately double the values
      estimated by GSPET. Despite the large disagreement, a small correlation (r=0.33,
      P=0.05) was observed for LVM between the two techniques. In conclusion, although
      we observed a good correlation for LV volumes and LVM between the GSPET and the
      ECHOC techniques, yet these two techniques cannot be used interchangeably.

PMID- 16894413
TI  - Diagnostic efficacy of technetium-99m pentavalent-dimercapto succinic acid versus
      gallium-67 citrate, imaging in patients with highly suspected acute bone and
      joint infections.
AB  - The purpose of this study was to evaluate and compare the diagnostic efficacy of
      (99m)Tc(V) dimercaptosuccinic acid ((99m)Tc(V)DMSA) with the (67)Ga-citrare
      ((67)Ga-C) scintigraphy in patients with suspected bone and joint infection.
      Thirty one patients, 19 men and 12 women, aged 18-78 y with median age 56 y, with
      suspected acute bone infection, were enrolled in this study. Besides (67)Ga-C and
      (99m)Tc(V)DMSA scintigraphy, all patients underwent X-ray radiography and
      technetium-99m methylene disphosphonate ((99m)Tc-MDP) bone scan for supporting
      the initial diagnosis. The (99m)Tc-MDP bone scan was considered positive for
      acute bone and joint infection when all its four scintigraphic phases were
      positive. Final diagnosis was based on needle aspiration and/or biopsy findings.
      Sensitivity, specificity, accuracy, positive and negative predictive values (PPV
      and NPV) were calculated. Our results have shown the following: Seventeen
      patients (17/31) had histologically confirmed acute bone and joint infections,
      while the remaining patients had no infection. (99m)Tc(V)DMSA diagnosed bone and
      joint infections in all positive (17/31) patients while (67)Ga-C in 16/31
      patients. Discordant scintigraphic results were observed by (67)Ga-C in 2/31
      cases: in one positive case of femur postoperative infection (false negative for
      (67)Ga-C) and in one case of clinicaly suspected infection in the femur while the
      patient had a preexisting fracture (false positive with (67)Ga-C). No false
      negative results were observed with (99m)Tc(V)DMSA. Sensitivity, specificity,
      PPV, NPV and accuracy were maximum for (99m)Tc(V)DMSA, while for (67)Ga-C were:
      94.1%, 93%, 94.1%, 93%, and 93.5% respectively. It is concluded that considering
      the high sensitivity and specificity of (99m)Tc(V)DMSA in the detection of acute
      bone and joint infections, the lower radiation dose, the cost and the shorter
      time spent for the imaging procedure, as compared to (67)Ga-C, (99m)Tc(V)DMSA
      should be preferred to (67)Ga-C as a bone scan agent for the detection of acute
      bone and joint infections.

PMID- 16894414
TI  - Sialocintigraphy versus ultrasonography of the salivary glands in patients first
      diagnosed with Sjogren's syndrome.
AB  - Sjogren's syndrome (SjS) is an autoimmune disease characterized by distraction of
      particularly salivary and lacrimal glands. The aim of the present study was to
      compare salivary gland scintigraphy (SGS) and salivary gland ultrasonography
      (SUS) in identifying salivary gland function in patients first diagnosed with
      SjS. We recruited 20 such patients with SjS (5 male, 15 female, aged from 35 to
      65 y, mean age 52, standard deviation: +/-5 y. All patients were submitted to SUS
      and SGS longitudinal and transverse images. Before the scintiscan, patients
      fasted for 6 h. Technetium-99m pertechnetate ((99m)Tc-PT) 110 MBq was injected
      intravenously (i.v.) and simultaneous multi-frames dynamic acquisition was
      performed for 30 min. In two patients who had discordant results between SUS and
      US, labial biopsy was performed. Dynamic acquisition curves for 30 sec for the
      parotid and the submandibular glands were generated. For each gland we have
      calculated: (a) the maximum uptake (MU): the ratio between the mean counts in the
      gland at 20 min and the background activity and (b) the outflow efficiency (OE):
      the ratio between the minimum counts after lemon juice stimulation at 30 min and
      the counts at 20 min. The results showed abnormal scintiscans with low MU and
      high OE in one or more of the glands, in 17/20 patients. These results were
      confirmed by SUS in 15 cases and in two cases labial biopsy confirmed the
      diagnosis made by SGS while SUS was negative. In the remaining 3/20 cases of SjS
      both tests, SUS and SGS, showed normal results. Discrepancies between SGS
      findings and labial biopsy as found in two of our cases have been reported by
      others and may be due among other causes to early lymphocytic infiltration in
      SjS. Normal findings of SGS have also been reported. In conclusion, in cases
      first diagnosed with SjS, the function of the parotid and the submandibular
      glands was better identified by the SGS as compared to SUS. Although SGS is a
      more complex and expensive examination, it should be preferred to SUS as more
      sensitive and indicating the stage of SjS.

PMID- 16894415
TI  - Thallium-201 single photon emission tomography after injecting an antimuscarinic
      agent compared with computed tomography for the diagnosis of recurrent colorectal
      cancer. Report of three cases.
AB  - Thallium-201 chloride ((201)TlCl) is frequently used for imaging of a variety of
      malignant tumors viz., thyroid, lung, brain, bone and breast, however in patients
      with colorectal cancer, its role is not well established. In this case report we
      present three patients with colorectal cancer recurrence, with inconclusive
      computed tomography (CT) findings while (201)TlCl single photon emission
      tomography (SPET) after injecting an anti-muscarinic agent, showed findings
      corroborating with the final diagnosis. Correlating CT with (201)TlCl-SPET
      findings, recurrence of the colorectal cancer was diagnosed in two cases;
      surgical treatment accordingly planned, confirmed the diagnosis. In the third
      case, CT was falsely positive while (201)TlCl-SPET was negative, compatible with
      the final diagnosis.

PMID- 16894416
TI  - A false negative by planar scintigraphy liver hemangioma, diagnosed by technetium
      99m-red blood cells and technetium-99m-sulfur colloid single photon emission
      tomography scan.
AB  - We present a 42-year-old patient who was examined in the Gastroenterology
      Department of Gaziantep University for chronic abdominal pain, nausea and
      vomiting. Ultrasonography showed a 4.7 cm solid hepatic mass on the right lateral
      side of the right lobe of the liver. The patient was then sent to the Nuclear
      Medicine Department of Gaziantep University for liver scan. After injecting
      autologous red blood cells labeled with 740 MBq of technetium-99m ((99m)Tc-RBC),
      early and delayed anterior planar images of the liver showed no significant
      findings because of the right kidney shine through the liver. Two days later,
      after injecting again 740 MBq of (99m)Tc-RBC, we performed a single photon
      emission tomography (SPET) scan but still this scan was nondiagnostic even in the
      delayed images of the liver. Three days later, after the iv injection of 185 MBq
      of technetium-99m-sulphur colloid ((99m)Tc-SC), we observed in the delayed SPET
      images of the liver, a mismatch defect with decreased focal uptake of (99m)Tc-SC
      at 60 min while the uptake of (99m)Tc-RBC at the same area was normal or slightly
      increased. The patient was then operated due to bleeding in the abdominal cavity.
      A cavernous hemangioma was found, confirmed by histology. The absorbed dose from
      all three diagnostic scanning procedures was: 4 mSv. In conclusion, the mismatch
      of the SPET delayed images between the (99m)Tc-RBC and the (99m)Tc-SC scans
      indicated that this procedure was effective for the diagnosis of liver cavernous
      hemangioma located in this unusual position.

PMID- 16894418
TI  - Metabolites of arachidonic acid in activating platelets and their estimation by
      radionuclide techniques.

PMID- 16894421
TI  - [Positron emission tomography in evaluating the response to treatment of brain
      tumors, lymphomas and breast cancer].
AB  - Positron emission tomography (PET) with the glucose analogue (18)F-FDG is
      increasingly used to monitor tumour response in patients undergoing chemotherapy,
      radiotherapy or new therapeutic schemes including antiangiogenesis and molecular
      targeted cancer treatment. PET as a functional imaging technology provides
      timely, quantitative, cross-sectional, non invasive assessment of several
      biologic processes targeted by the above-mentioned therapies. Tests by the camera
      PET can be useful in distinguishing between radiation necrosis or scarring and
      tumour recurrence, thus evaluating response to therapy. The information provided
      by this technique is more sensitive and specific than that provided by
      conventional anatomic imaging modalities such as computerised tomography,
      magnetic resonance imaging or ultrasound and superior in evaluating the
      effectiveness of various treatment regimens early during therapy or after the
      completion of therapy. With this information in hand, physicians can modify
      ineffective therapy and consequently improve patient's outcome and reduce the
      cost of treatment. In the present review article we discuss the contribution of
      tests performed by the PET camera, mainly using (18)F-FDG as a radiotracer, in
      the evaluation of treatment response in patients with brain tumours, lymphomas
      and breast cancer.

PMID- 16894419
TI  - Our experience from radioiodine-131 treatment and whole body scintigraphy
      findings in 357 patients with metastatic differentiated thyroid carcinoma after
      surgical ablation.

PMID- 16894422
TI  - [Specified systems of high spatial resolution for tomographic gamma cameras;
      their applications and studies in Greece].
AB  - Imaging with nuclear medicine planar and tomographic gamma cameras, offers
      information about the function of an organ, the detection and the delineation of
      a lesion. However, the basic limitations of these cameras are low statistics, the
      significant noise (background), the relatively low spatial resolution and low
      sensitivity. Moreover, commercially available systems are large, since they are
      constructed for general clinical use only and so, small organs such as brain,
      heart, breast, prostate etc cannot be efficiently imaged. For these reasons a
      number of dedicated imaging systems have been developed, based on modifications
      of the existing technology or on novel technology. One important limitation in
      using such systems routinely is their high cost. The most important applications
      of these new systems are focused on imaging small animals or small human organs,
      on scintimammography, on sentinel node detection and for the evaluation of new
      radiopharmaceuticals. In the present work, the principles of operation of these
      dedicated SPET imaging systems, results from clinical trials and present Greek
      studies, are presented.

PMID- 16894423
TI  - [Comparison of six radionuclidic and non-radionuclidic methods for the assessment
      of glomerular filtration rate in patients with chronic renal failure].
AB  - The assessment of renal function in patients with chronic renal failure has a
      significant impact on both prognosis and treatment. We were unable to find a
      study, comparing six radionuclidic and non-radionuclidic methods as tested in
      this study on the same patients for the assessment of renal function in order to
      evaluate the relative significance of each method. In this study 82 patients were
      enrolled, 31 females with an age range 18-73 y (mean: 46 y) and 51 males with an
      age range 20-77 y (mean: 48 y). The level of renal function of these subjects
      ranged between normal, and mild to severe renal failure with serum creatinine
      levels: 2.7+/-2.2 mg/dl (mean+/-SD). The methods used for the glomerular
      filtration rate (GFR) were: (a) the clearance of inulin; (b) the technetium 99m
      labeled-diethyleno triamine pentacetic acid (99m)Tc-DTPA plasma disappearance
      curve; (c) the UV/P formula, not corrected for the residual urine volume in the
      bladder [DTPA(-)]; (d) the UV/P formula corrected for the residual urine volume
      in the bladder [DTPA(+)]; (e) plasma clearance of creatinine by the Cockcroft
      Gault formula; and (f) plasma clearance of creatinine by using a 24-hour urine
      collection. In a subgroup of 13/82 patients, GFR was assessed by the
      radionuclidic and non-radionuclidic methods and compared against clearance of
      inulin, which was considered to be the gold standard. Moreover, we evaluated in
      our results the impact of age, gender, cause and stage of renal failure and the
      effect of the residual urine volume in the bladder. Fifteen of our patients were
      re-evaluated after 19-21 weeks. Spearman's correlation was used for statistical
      analysis; a two-sided P value < 0.05 was considered as statistically significant.
      Our results have shown that: the DTPA(+) method displayed the best correlation
      with the clearance of inulin (r=0.996) and was considered as the reference method
      in this study. The radionuclidic methods (99m)Tc-DTPA) plasma disappearance curve
      and DTPA(-) gave similar and comparable results with DTPA(+) (r=0.98, r=0.96),
      while the non-radionuclidic methods(plasma clearance of creatinine by using a 24
      hour urine collection and plasma clearance of creatinine by the Cockcroft-Gault
      formula) tended to overestimate GFR respectively(r=0.91, r=0.79). Patient's age
      and gender had no impact on the calculated GFR values. With regards to the
      chronic renal failure cause, the above-mentioned tendencies were confirmed in
      primary and secondary glomerulonephritis, in diabetic nephropathy, and in
      hereditary renal diseases. On the contrary, in patients with renal disease of
      unknown cause, all methods -- isotopic and non-isotopic -- gave comparable
      results. The DTPA(-) method is simple to use and reliable, however, due to the
      fact that it does not consider the residual urine volume in the bladder, it seems
      to overestimate GFR in elderly men with prostate hypertrophy and increased
      residual urine volume in the bladder. The DTPA(+) method is reliable in a wide
      range of renal function levels, from mild to significant renal impairment. The
      radionuclidic methods DTPA(+), DTPA(-) and the (99m)Tc-DTPA plasma disappearance
      curves showed a very good reproducibility (r =0.97, r =0.96, r = 0.87) when were
      reperformed after 19-21 weeks, as compared to creatinine clearance with 24-hour
      urine collection (r=0.83). In conclusion, the radionuclidic methods in patients
      with chronic renal failure are reliable and reproducible, closely resembling
      those of inulin clearance. The among all radionuclidic methods, (99m)Tc-DTPA(+)
      shows the best results.

PMID- 16894424
TI  - [Proposals for the revision of radiation protection measures for doses up to 222
      MBq iodine-131 for whole body scintiscan for the detection of metastatic
      lesions].
AB  - The goal of this study was to estimate the necessary period of time, required for
      radiation protection instructions to be followed by patients with differentiated
      thyroid carcinoma (DTC) after total thyroidectomy who are given iodine-131
      ((131)I) for a whole body scintiscan (WBS) in relation to the instructions of the
      European Commission and the ICRP. In order to estimate and evaluate the dose
      received by the family members and the general public, we have studied 30
      patients and were given a dose of 92-222 MBq of (131)I for a diagnostic WBS. The
      patients studied were four men with mean age+/-standard deviation (M+/-SD)=55+/-6
      y and 26 women with: M+/-SD=47+/-14 y. Dose rate measurements were carried out at
      the Nuclear Medicine Department of the AHEPA University Hospital; 1 h after the
      patients had received the (131)I dose and 48 h later when they returned to the
      hospital for the WBS. The calculated doses received by the in-living relatives of
      the patients and by the general public, assuming that radiation protection
      measures were applied for 2d, ranged between 76-640 microSv and 22-171 microSv
      respectively. In conclusion, the results of this study, compared to the dose
      constraints suggested by the European Commission, indicate that the duration of
      radiation protection guidelines for patients receiving (131)I for diagnostic
      purposes could be reduced to only two days without any potential risk to family
      members or to members of the public. The case of children of the immediate family
      environment, aged less than 3 y, was not investigated in this study.

PMID- 16894425
TI  - [Brown tumors in the technetium-99m methyldiphosphonate bone scan mimicking
      metastases of parathyroid carcinoma].
AB  - This is a case of a 78 year old male with parathyroid carcinoma and multiple bone
      lesions in the technetium-99m methyldiphosphonate ((99m)Tc-MDP) bone scan,
      initially interpreted as metastatic bone disease, but finally proved to be brown
      tumors. The interest of this case lies on the rarity of the disease, as well as
      the co-existence of osteitis fibrosa cystica, which often resembles metastatic
      bone disease and leads to diagnostic pitfalls.

PMID- 16894426
TI  - BMI of Australian general practice patients.
AB  - The BEACH program, a continuous national study of general practice activity in
      Australia, gathers height and weight details of patients at 40% of recorded
      encounters, enabling their body mass index to be calculated. Details are self
      reported by the patients, or by their carer in the case of young children, and
      recorded by the general practitioner at the encounter. This synopsis provides a
      backdrop against which the articles in this issue of Australian Family Physician
      can be further considered.

PMID- 16894427
TI  - If not dieting, now what?
AB  - BACKGROUND: Helping patients to achieve and maintain their most healthy weight is
      a common challenge. Giving a "one size fits all" set of instructions to patients
      who are over their most healthy weight does not help. OBJECTIVE: This article
      discusses approaches to assist weight loss in patients while treating each
      patient as an individual. DISCUSSION: By using less emotive, more supportive and
      accepting language, we can still talk about reality (for example "a patient being
      above their most healthy weight") while minimising the risk of negatively
      impacting on the patient's self esteem. It is important to spend time learning
      from the patient, factors that have influenced their relationship with their body
      and weight, and the reasons why that person's weight has become above their most
      healthy weight range. We need to help patients focus on changes to their
      thinking, attitude and behaviour with weight loss to come as a result of that.
      Motivational interviewing is a useful counselling approach. It is also helpful to
      have a range of options to offer patients. This may include reading resources; a
      team of health professionals to refer to such as dieticians, counsellors,
      physiotherapists, and exercise specialists; or appropriate community group
      programs.

PMID- 16894428
TI  - Weight loss medications--where do they fit in?
AB  - BACKGROUND: Obesity is a chronic disease requiring a similar long term approach
      to management as that of other chronic conditions. OBJECTIVE: This article
      discusses the role of medications in the overall management of obesity.
      DISCUSSION: Management needs to be multifaceted, aiming to alter the patient and
      family micro-environment to one favouring better weight control through
      sustainable behavioural changes to physical activity and diet. Weight loss
      medications may provide additional benefit. Currently we have only two
      medications suitable for long term therapy--orlistat and sibutramine.
      Sibutramine, which acts centrally to suppress appetite, has shown efficacy for up
      to 2 years. Orlistat, a lipase inhibitor, reduces fat absorption and has been
      shown to reduce and maintain weight for up to 4 years. The effect of these
      medications is modest, generally providing less than 5 kg weight loss when
      compared with placebo. Patients need to have realistic expectations and
      understand the benefits of sustained modest weight loss. It is important that
      weight loss medications are prescribed in combination with lifestyle
      modification.

PMID- 16894429
TI  - The science behind weight loss diets--a brief review.
AB  - BACKGROUND: Controversy surrounds both the Atkins diet and moderate carbohydrate,
      high protein diets. OBJECTIVE: This article undertakes a brief review of the
      evidence for efficacy and possible harmful effects of various popular diets.
      DISCUSSION: Low fat diets have been shown to reduce weight at 12 months and have
      additional benefits of high fibre intake and may reduce the risk of diabetes.
      However, many people cannot maintain these diets long term so new solutions have
      been sought. Surprisingly, trials have only appeared over the past 3-4 years
      evaluating the effects of the Atkins diet, and these have shown weight loss
      benefits at 6 months, but the benefit is lost by 12 months. Adherence to this
      regimen is difficult. Problems include constipation from the relatively low fibre
      intake and a less than expected rise in LDL cholesterol. A moderate carbohydrate,
      high protein diet has been shown to maintain weight loss at 12 months and beyond,
      with improvements in cardiovascular risk factors and little risk of long term
      side effects. Patient choice will depend on dietary preferences and previous
      experiences with diets. Those with metabolic syndrome might benefit more from
      carbohydrate restriction.

PMID- 16894430
TI  - Management of obesity--the role of surgery.
AB  - BACKGROUND: Obesity is rapidly becoming Australia's biggest health care issue.
      OBJECTIVE: This article discusses the role of surgery, in particular laparascopic
      adjustable gastric banding, in the management of obesity. DISCUSSION: The
      acceptability and uptake of surgery as a solution to obesity has, in the past,
      been low. This is largely due to the risks of bypass and stapling procedures, as
      well as the lack of long term efficacy. Laparoscopic adjustable gastric banding
      has, over the past 13 years, proven not only to be safe, but effective both in
      terms of weight loss and control of the comorbidities associated with obesity. It
      is currently the most effective solution we have available for patients who
      suffer from obesity.

PMID- 16894432
TI  - Cholesterol--frequently asked questions.

PMID- 16894431
TI  - Individualising weight loss prescription--a management tool for clinicians.
AB  - BACKGROUND: Obesity is a global epidemic and a growing cause of comorbidities
      seen by clinicians. Yet apart from recent guidelines developed by the National
      Health and Medical Research Council there are few clinical tools available to
      tackle this problem. OBJECTIVE: This article describes a tool for detecting
      aspects of both diet and lifestyle likely to adversely affect the body weight of
      an individual. DISCUSSION: The Diet, Activity and Behaviour Questionnaire (DAB-Q)
      is designed to identify the nutrition, physical activity and eating behaviours
      likely to lead to energy imbalance and increased body weight in an individual.
      This tool can be used in clinical practice to help individualise appropriate
      behavioural prescriptions for successful weight management.

PMID- 16894433
TI  - The role of physiotherapy in weight control.

PMID- 16894434
TI  - Dysplastic melanocytic naevus syndrome.

PMID- 16894435
TI  - Complementary medicines and weight management.

PMID- 16894436
TI  - Dengue fever and dengue haemorrhagic fever--a diagnostic challenge.
AB  - The number of cases of dengue fever in returning travellers is increasing
      worldwide. In Australia, two mosquito vectors exist and the Aedes aegypti
      mosquito has already been responsible for local transmission within Queensland.
      For these reasons, general practitioners need to be able to recognise dengue
      fever and its complications: dengue haemorrhagic fever (DHF) and dengue shock
      syndrome. Infections can vary from severe to asymptomatic. The incubation period,
      duration of fevers, presence of rash and relative bradycardia can assist in the
      diagnosis of dengue. Dengue haemorrhagic fever is a severe form of dengue fever
      associated with plasma leakage and specific risk factors. The risk of DHF to most
      travellers previously infected with dengue is probably low. Serology and reverse
      transcriptase polymerase chain reaction are useful tests for diagnosing
      infection, although both have limitations. Vaccine design is a promising strategy
      to prevent infection.

PMID- 16894437
TI  - Acne--natural history, facts and myths.
AB  - This article describes the epidemiology and natural history of acne and discusses
      the common aetiological myths and beliefs surrounding acne. Acne is a polymorphic
      disease with noninflammatory and inflammatory aspects and a wide spectrum of
      severity. The severe inflammatory patterns tend to be those that most frequently
      scar and therefore require early intervention. The pattern of disease, relative
      severity, distribution, and patient's social circumstances will influence
      appropriate management. However, effective management also includes patient
      education about acne, its natural history, and dispelling acne myths.

PMID- 16894438
TI  - Australia's Vietnam veterans--a review.
AB  - BACKGROUND: Vietnam veterans' war experiences have adversely affected their own
      mental health and that of one in 3 partners and one in 4-6 of their dependents,
      many of whom are reluctant to seek help. OBJECTIVE: This article reviews the
      health problems suffered by families of Australia's Vietnam veterans and
      discusses what the future might hold for these families, what the implications
      might be for families of veterans of more recent conflicts, and how general
      practitioners and divisions of general practice might help. DISCUSSION: Mental
      illness of veterans' dependents may increase their risk of cardiovascular and
      other physical diseases, and their children's risk of psychological problems.
      Caring for veterans as they age may further strain the mental health of one in 3
      4 partners and jeopardise their role as grandparents. General practitioners can
      help by paying attention to the mental health of veterans and their dependents,
      working with the families, providing education and support, assessing the need
      for individual or family counselling, encouraging veterans' dependents to use
      universal or Department of Veterans' Affairs services, and building dependent's
      and grandchildren's resilience.

PMID- 16894439
TI  - Belonephobia--a fear of needles.
AB  - Belonephobia is an unreasonable and altered response due to the fear of needles.
      It affects up to 10% of the population and has implications for treatment and
      follow up, especially in the paediatric setting (see Case study). A three step
      behavioural approach involving recognition and relaxation, control and
      preparation, and graded exposure, can be effective in overcoming belonephobia.
      This will assist with non-urgent minor procedures being undertaken.

PMID- 16894440
TI  - Evidence based answers--is salmeterol safe in asthma?

PMID- 16894441
TI  - "Wrongful life" claims.
AB  - On 9 May 2006, the High Court of Australia dismissed "wrongful life" claims
      brought on behalf of two patients. One of the cases involved the alleged
      negligent failure by a general practitioner to diagnose prenatal rubella and to
      advise the mother of the risks to the fetus associated with rubella. This article
      outlines the case and discusses the nature of "wrongful life" and "wrongful
      birth" claims.

PMID- 16894442
TI  - Interpreting and understanding meta-analysis graphs--a practical guide.
AB  - Ideally, clinical decision making ought to be based on the latest evidence
      available. However, to keep abreast with the continuously increasing number of
      publications in health research, a primary health care professional would need to
      read an insurmountable number of articles every day covered in more than 13
      million references and over 4800 biomedical and health journals in Medline alone.
      With the view to address this challenge, the systematic review method was
      developed. This article provides a practical guide for appraising systematic
      reviews for relevance to clinical practice and interpreting meta-analysis graphs
      as part of quantitative systematic reviews.

PMID- 16894443
TI  - Balint groups--an Australian perspective.
AB  - Balint groups are an important, internationally established method of training
      general practitioners in the psychological aspects of their work. Small groups of
      GPs meet regularly with a trained leader to discuss clinical material from their
      practices, with a focus on the doctor-patient relationship. This article explains
      the Balint group model and its benefits and describes what is known about Balint
      groups in Australia, including avenues for Balint group experience available to
      Australian GPs.

PMID- 16894444
TI  - When symptoms of disease overlap with symptoms of depression.
AB  - BACKGROUND: The diagnosis of depression is often dependent on somatic symptoms
      which overlap with the symptoms of many medical illnesses. METHOD: We analysed
      tape recorded interviews of 46 out of 61 eligible community dwelling older adults
      with advanced disease and many somatic symptoms of depression. Participants
      answered an open question about feelings, and structured questions about symptoms
      of depression. RESULTS: Twenty-four (39%) patients met DSM-IV symptom criteria
      for depression when somatic symptoms were included, and only 1 (2%) when they
      were excluded. Of the 24, 22 (92%) reported two or more psychological symptoms of
      depression and 14 of the 17 (82%) for whom transcripts were available disclosed
      feelings of psychological distress. DISCUSSION: Although every older adult with
      advanced disease reported somatic symptoms of depression, most did not meet DSM
      IV criteria of depression even when all somatic symptoms are included. Including
      somatic symptoms accurately identifies patients who warrant follow up when
      psychological distress in unstructured interviews is used as the gold standard.
      There is no need to exclude somatic symptoms when considering a diagnosis of
      major depression in medical patients.

PMID- 16894445
TI  - Initiating a PDSA cycle--improving management of diabetes in rural WA.
AB  - Diabetes affects 1 million Australians and is the seventh leading cause of death
      in Australia. General practitioners play an important role in the management of
      diabetes, especially in rural areas where there is limited access to specialist
      providers and services.

PMID- 16894446
TI  - Assessing whiplash recovery--the Whiplash Disability Questionnaire.
AB  - BACKGROUND: General practitioners often need to track outcomes of whiplash
      patients, and a disability questionnaire may be useful. METHODS: Whiplash
      patients who attended primary care clinics in Edmonton, Canada were interviewed 3
      months postcollision. Subjects were asked a global recovery question: "Do you
      feel you have recovered fully from your accident injuries?" Subjects then
      completed the Whiplash Disability Questionnaire (WDQ). RESULTS: A total of 131
      subjects participated. Of these, 52 (39.7%) reported that they felt they had
      recovered. Those who reported complete recovery had a mean WDQ score of 2.5 and
      those who reported they had not recovered had a mean WDQ score of 29.9. All who
      responded "yes" to the recovery question had a WDQ score below 13, while all
      those responding "no" to the recovery question had a WDQ score of 13 or more.
      DISCUSSION: The WDQ as an outcome measure may be useful in clinical practice.

PMID- 16894448
TI  - Outcome studies of pulmonary embolism versus accuracy: they do not equate.

PMID- 16894449
TI  - Ovarian vein thrombosis and its relevance in the daily clinical management for
      hospitalised patients.

PMID- 16894450
TI  - Arterial disease and venous thromboembolism: a modern paradigm?

PMID- 16894451
TI  - Inhibitors in mild/moderate haemophilia A: an update.
AB  - The development of inhibitors in patients with mild/moderate hemophilia A is an
      increasingly recognized occurrence and is manifested by the patients' bleeding
      pattern becoming more severe. Inherited (hemophilia genetic mutations) and
      acquired (type and delivery of factor VIII replacement therapy) factors have been
      associated with an increased likelihood of developing factor VIII inhibitors.
      Although the use of bypassing agents (i.e. activated prothrombin complex
      concentrates and recombinant factor VII activated) has been demonstrated to be
      effective in controlling bleeding episodes in patients who develop factor VIII
      inhibitors, the limited data available in the literature are insufficient to
      determine the optimal approach to the eradication of inhibitors (i.e. immune
      tolerance induction, immunosuppression or both) for this group. Particular
      attention should be directed to the prevention of this complication in those
      patients with mild/moderate hemophilia recognized to be at increased risk of
      developing a factor VIII inhibitor. In conclusion, large prospective trials are
      warranted in order to elucidate the many still unclear pathogenic and therapeutic
      aspects of the development of inhibitors in patients with mild/moderate
      hemophilia A.

PMID- 16894452
TI  - The efficacy of rituximab in the treatment of inhibitor-associated hemostatic
      disorders.
AB  - Rituximab is a chimeric anti-CD20 monoclonal antibody active against normal and
      malignant B cells which has proven to be effective in the therapy of CD-20
      positive lymphomas. Its B-cell cytotoxic action has also been exploited in many
      non-malignant autoimmune disorders in which it has been used with the aim of
      interfering with the production of pathologic antibodies. The present knowledge
      regarding the use of rituximab in antibody-associated disorders of hemostasis
      (i.e. idiopathic thrombocytopenic purpura, thrombotic thrombocytopenic purpura,
      acquired hemophilia A, congenital hemophilia with inhibitors, acquired inhibitors
      against coagulation factors) is presented briefly in this review. The results
      suggest that rituximab can be useful in the treatment of disorders of hemostasis
      associated with inhibitor formation. Although collectively the number of patients
      treated is now quite substantial, most of the data are drawn from isolated case
      reports or descriptions of small, uncontrolled series. Large, prospective,
      randomized trials are, therefore, needed to confirm the positive, preliminary
      results.

PMID- 16894453
TI  - Ovarian vein thrombosis: incidence of recurrent venous thromboembolism and
      survival.
AB  - For patients with ovarian vein thrombosis (OVT), neither the rate of recurrence
      nor the expected survival are well established. Clarification of these natural
      history data would aid in defining the optimal management. We studied all female
      patients with OVT seen at the Mayo Clinic between 1990 and 2006. Survival,
      recurrent venous thrombosis rates, and prothrombotic factors were compared to a
      randomly selected group of 114 female patients with lower extremity venous
      thrombosis (DVT). Patients with OVT (n = 35; mean age 44.8 +/- 17.9 years) were
      significantly more likely to be under hormonal stimulation (48%), have an
      underlying malignancy (34%), experienced recent pelvic infection (23%) or
      undergone recent surgery (20%), compared to DVT patients. During a mean follow-up
      period of 34.6 +/- 44.3 months, three patients suffered three recurrent venous
      thrombi (event rate: three per 100 patient years of follow-up). This recurrence
      rate was comparable to patients with lower extremity DVT (2.2 per 100 patient
      years). Recurrent thrombosis involved the contralateral ovarian vein, left renal
      vein, and inferior vena cava. The five-year mortality rate for OVT patients was
      43% compared to 20% for DVT patients (p = 0.08). All OVT deaths were cancer
      related. Survival was greater in OVT patients without cancer compared to those
      with active cancer (p < 0.0001). In conclusion, venous thromboembolism recurrence
      rates are low and comparable to lower extremity DVT. Therefore general treatment
      guidelines for lower extremity DVT may be applicable. Poor survival rates in OVT
      are principally governed by the presence of malignancy.

PMID- 16894454
TI  - Incidence of arterial cardiovascular events in patients with idiopathic venous
      thromboembolism. A retrospective cohort study.
AB  - Recent data have shown a higher incidence of arterial events in patients with
      venous thromboembolism (VTE) of unknown origin than in those with the secondary
      form of disease. Whether patients with idiopathic VTE have a higher risk of
      subsequent arterial events than the general population is unknown. The aim was to
      evaluate the rates of subsequent arterial events in patients with idiopathic VTE
      and control subjects. In a retrospective cohort study we compared the rates of
      subsequent arterial events (i.e. acute myocardial infarction, ischemic stroke and
      peripheral arterial disease) in 151 consecutive patients with objectively
      confirmed spontaneous VTE and 151 control subjects randomly selected from the
      database of two family physicians. We collected information about cardiovascular
      risk-factors (hypertension, hypercholesterolemia, diabetes, obesity and smoke) at
      the time of VTE episode, or corresponding date for the controls, and considered
      the follow-up from this time. Patients and controls who had suffered from
      arterial events before the index date were excluded. During a mean follow-up of
      43.1 (+/- 21.7) months there were 16 arterial events in the VTE patients and six
      in the control group (HR, 2.84;95% CI,1.11 to 7.27; p = 0.03). The difference
      remained significant after adjusting for age and other cardiovascular risk
      factors (HR 2.86;95% CI,1.07 to 7.62). Overall mortality was also higher in the
      VTE patients (12 vs.4 deaths). In conclusion, arterial events are more common in
      patients with previous idiopathic VTE than in the general population. These
      findings may have practical implications.

PMID- 16894455
TI  - Warfarin-related outcomes in patients with antiphospholipid antibody syndrome
      managed in an anticoagulation clinic.
AB  - Patients with antiphospholipid antibody syndrome (APA) are at elevated risk of
      venous and arterial thromboembolic complications. Oral anticoagulation with
      warfarin is recommended for secondary prevention of thromboembolism, but warfarin
      related outcomes have not been systematically investigated when warfarin therapy
      is managed by a dedicated anticoagulation clinic. The objectives of the study
      were to evaluate warfarin-related monitoring outcomes, clinical endpoints and the
      use of healthcare resources as a result of warfarin-related complications in
      patients with APA compared to a group of patients without APA, all of whom were
      managed in an anticoagulation clinic setting. A retrospective observational
      cohort design was used to investigate patients with and without APA, all of whom
      had a history of venous or arterial thromboembolism, and were matched for age,
      gender and indication for oral anticoagulation. Thirty-six APA patients taking
      warfarin were compared to a matched cohort of 36 patients without APA. Monitoring
      outcomes (time in therapeutic range, clinic visits per year, frequency of
      warfarin dosing adjustments, reasons for out-of-range INRs) were similar between
      groups, as was the frequency of major bleeding complications (3.2%/pt-yr vs.
      3.1%/pt-yr). However, recurrent thromboembolic events (9.6%/pt-yr vs 0) occurred
      more frequently in APA patients. APA patients required more emergency room visits
      (6.4%/pt-yr vs. 1.6%/pt-yr) and hospital admissions (14.4%/pt-yr vs.3.0%/pt-yr)
      to manage complications of warfarin therapy. In conclusion, despite similar
      monitoring outcomes obtained in a dedicated anticoagulation clinic setting,
      adverse clinical outcomes are significantly more frequent in patients with APA
      syndrome than in those without APA, and require more frequent use of healthcare
      resources.

PMID- 16894456
TI  - Exchange transfusion activates coagulation and alters the coagulation profile in
      newborn infants.
AB  - Exchange transfusion (ET) with adult blood is a standard procedure for neonates
      with severe hyperbilirubinemia. How ET affects newborn coagulation system
      remains, however, largely unknown. Thus, we prospectively evaluated the effect of
      ET on thrombin formation and coagulation profile in 18 newborns (22 ETs).
      Prothrombin fragment F1+2 and thrombin-antithrombin complexes increased
      considerably during ET while platelets were significantly reduced. Protein C
      increased less (p < 0.001) and factor VIIIc more (p < 0.001) than expected based
      on their levels in the infused blood. Further, in vitro thrombin generation
      initiated by 5 pM tissue factor was analysed. Before the first ET, newborn
      endogenous thrombin potential (ETP) and thrombin peak remained at approximately
      60% of adult control plasma levels, but the lag time to thrombin burst in newborn
      plasma was approximately 45% shorter than the lag time in adult plasma. At the
      end of the first ET, the thrombin burst still started approximately 35% earlier
      in newborn than adult plasma, whereas ETP and thrombin peak were increased to >
      90% of adult levels. ETP and peak remained elevated at adult levels until the
      beginning of the second ET. APC-induced reductions in newborn ETP remained
      unaltered throughout the first ET. The reductions of ETP by APC were less
      pronounced in newborn than adult plasma (p < 0.0001). We conclude that ET is
      associated with multiple procoagulant changes and increased in vivo thrombin
      formation. This ET-induced procoagulant challenge may be of clinical significance
      in sick newborns already prone to bleeding and thrombotic complications.

PMID- 16894457
TI  - Prevention effect of orally active heparin derivative on deep vein thrombosis.
AB  - The use of heparin as the most potent anticoagulant for the prevention of deep
      vein thrombosis and pulmonary embolism is nevertheless limited, because it is
      available to patients only by parenteral administration. Toward overcoming this
      limitation in the use of heparin, we have previously developed an orally active
      heparin-deoxycholic acid conjugate (LMWH-DOCA) in 10% DMSO formulation. The
      present study evaluates the anti-thrombogenic effect of this orally active LMWH
      DOCA using a venous thrombosis animal model with Sprague-Dawley rats. When 5
      mg/kg of LMWH-DOCA was orally administered in rats, the maximum anti-FXa activity
      in plasma was 0.35 +/- 0.02, and anti-FXa activity in plasma was maintained above
      0.1 IU/ml [the minimum effective anti-FXa activity for the prevention of deep
      venous thrombosis (DVT) and pulmonary embolism (PE)] for five hours. LMWH-DOCA (5
      mg/kg, 430 IU/kg) that was orally administered reduced the thrombus formation by
      56.3 +/- 19.8%;on the other hand, subcutaneously administered enoxaparin (100
      IU/kg) reduced the thrombus formation by 36.4 +/- 14.5%. Also, LMWH-DOCA was
      effectively neutralized by protamine that was used as an antidote. Therefore,
      orally active LMWH-DOCA could be proposed as a new drug that is effective for the
      longterm prevention of DVT and PE.

PMID- 16894458
TI  - Association of homocysteine (but not of MTHFR 677 C>T, MTR 2756 A>G, MTRR 66 A>G
      and TCN2 776 C>G) with ischaemic cerebrovascular disease in Sicily.
AB  - Association between methylenetetrahydrofolate reductase polymorphism (MTHFR 677
      C>T ), a determinant of homocysteine plasma level (t-Hcys), with ischaemc
      cerebrovascular disease (iCVD) seems to be neutral in North Europe and North
      America. The association of 2756 A>G of methionine synthase (MTR), 66 A>G of
      methionine synthase reductase (MTRR) and 776 C>G of transcobalamin ( TCN2 ) needs
      to be evaluated further. It was the objective of this study to evaluate the
      association of these polymorphisms, t-Hcys, vitamin B12 and folate levels with
      iCVD, in an Italian population from Sicily. We investigated the association of
      these polymorphisms, t-Hcys, vitamin B12 and folate with iCVD in 252 subjects,
      including 131 cases and 121 sex- and age-matched healthy controls. t-Hcys was
      higher in the iCVD group than in controls [15.3 (11.5 - 17.9) vs. 11.6 (9.4 -
      14.5) microM; P = 0.0007] and also in subjects with TCN2 776CG genotype, compared
      to homozygous genotypes [13.5 (9.9 +/- 16.9) vs. 11.7 (9.6 +/- 14.4) microM; P =
      0.0327]. The folate level in cases and controls was consistent with an adequate
      dietary intake [12.7 (9.0 - 15.3) vs. 12.5 (9.6 - 16.9) nM; P = 0.7203]. In
      multivariate analysis, t-Hcys was a significant independent predictor of iCVD
      with an odds ratio of 1.14 (95 % C.I.: 1.06 - 1.24; P = 0.0006). No association
      was found between MTHFR, MTR, MTRR and TCN2 polymorphisms and iCVD risk. We have
      found an influence of t-Hcys and a neutral effect of MTHFR, MTR, MTRR and TCN2 on
      iCVD risk in Sicily. The neutral influence of these polymorphisms may be
      explained by adequate status in folate and vitamin B12. Other factors underlying
      the increased t-Hcys need further investigations.

PMID- 16894459
TI  - ADAMTS-13 regulates platelet adhesion under flow. A new method for
      differentiation between inherited and acquired thrombotic thrombocytopenic
      purpura.
AB  - ADAMTS-13 cleaves large and ultra-large von Willebrand factor multimers normally
      secreted by endothelial cells. Severe deficiency of this enzyme leads to
      thrombotic thrombocytopenic purpura (TTP). We applied the Impact-R system [Cone
      and plate(let) Analyzer, CPA] to determine optimal conditions for ADAMTS-13
      function, to assess it's activity in TTP patients and to distinguish inherited
      TTP (inTTP) from acquired TTP (acTTP). The role of ADAMTS-13 in platelet adhesion
      under different conditions was investigated applying recombinant forms of VWF and
      ADAMTS-13. rVWF was first treated by rADAMTS-13 either in solution or when
      immobilized on the surface of the well, under static or flow conditions, in the
      presence or absence of BaCl2. The resulting cleaved VWF fragments were then
      immobilized and served to assess type 3 von Willebrand disease whole blood
      platelet adhesion under flow. Maximal effect of the rADAMTS-13 (decrease of
      platelet adhesion in the absence compared to the presence of BaCl2), was observed
      when the rVWF was pre-immobilized and the cleavage step took place under flow
      (85%). Mixing plasma ofTTP patients with normal blood (1:3) yielded a 1.6- to 2
      fold increase of platelet adhesion under flow compared to mixing normal plasma
      with normal blood, at shear rate range of 1,800 - 2,500 s(-1) . Maximal increase
      of platelet adhesion was observed under 2,050 s(-1) . Under these conditions, the
      extent of adhesion was similarly higher in patients with inTTP and acTTP versus
      control [surface coverage (SC) 14.5 +/- 2.8% and 14.6 +/- 2.5% vs.7.4 +/- 1.7%,
      respectively]. ADAMTS-13 activity measured by collagen-binding test was similarly
      low (4.2 +/- 3.8% and 3.5 +/- 2.4% vs. 72.2 +/- 8.0%, respectively). An inverse
      correlation between SC and ADAMTS-13 activity was observed in a patient with
      inTTP assayed eight times during plasma infusion treatment. Addition of BaCl2 to
      the mixture of TTP plasma and normal whole blood yielded a decrease in platelet
      adhesion in inTTP (by 51%) but not in acTTP. The lack of reduction of platelet
      adhesion in acTTP could presumably be due to the presence of ADAMTS-13 inhibitor
      in these patients. These results suggest that VWF immobilization and high shear
      flow yielded optimal conditions for ADAMTS-13 activity, and that introduction of
      BaCl2 in the Impact-R (CPA) test may be useful for differentiation between
      inherited and acquired TTP.

PMID- 16894460
TI  - Ex vivo evaluation of anti-GPVI antibody in cynomolgus monkeys: dissociation
      between anti-platelet aggregatory effect and bleeding time.
AB  - Recent progress in the understanding of thrombus formation has suggested an
      important role of glycoprotein (GP)VI. In contrast to its pivotal role in
      collagen-induced platelet activation, it has been suggested that its blockade
      does not induce massive bleeding tendency. To demonstrate the dissociation
      between inhibitory effect on platelet aggregation and bleeding by GPVI blockade,
      we examined the effects of Fab fragment of OM2, an anti-human GPVI monoclonal
      antibody on ex vivo collagen-induced platelet aggregation and skin bleeding time
      after intravenous injection in cynomolgus monkeys. In a dose-escalation study,
      OM2 potently (> 80%) inhibited collagen-induced platelet aggregation at the
      cumulative dose of 0.2 mg/kg with a slight prolongation of bleeding time (1.3
      times baseline value). Furthermore, at 18.8 mg/kg, the highest dose tested,
      prolongation of bleeding time was still mild (1.9 times). In contrast, abciximab,
      Fab fragment of anti-GPIIb/IIIa antibody prolonged bleeding time by 5.0 times at
      0.35 mg/kg, the lowest effective dose on platelet aggregation. In a
      pharmacodynamic study, a bolus injection of OM2 at 0.4 mg/kg produced potent
      inhibition of collagen-induced aggregation up to six hours after injection,
      showing longer half-life than that of abciximab. The injection of OM2 Fab did not
      induce thrombocytopenia and GPVI depletion in monkeys. These results suggest that
      blockade of GPVI by antibody can exert a potent inhibitory effect on collagen
      induced platelet aggregation with a milder prolongation of bleeding time than
      blockade of GPIIb/IIIa. This study indicates that OM2 has the potential to be
      developed as a new class of therapeutic tool.

PMID- 16894461
TI  - Leukemic lymphoblasts, a novel expression site of coagulation factor XIII subunit
      A.
AB  - Blood coagulation factor XIII (FXIII) is a protransglutaminase circulating as a
      tetramer formed by two types of subunits (A2B2). The intracellular dimeric form
      of FXIII (A2) is present in platelets, megakaryocytes, monocytes and macrophages
      and has been detected in mono- and megakaryocytic leukemias. The aim of our study
      was to investigate FXIII-A expression in newly diagnosed B cell acute
      lymphoblastic leukemia (ALL) samples. We examined 47 de novo ALL cases of B cell
      origin by triple color labeling with flow cytometry. FXIII-A was detected by a
      FITC conjugated monoclonal antibody combined with CD34 and CD45 staining. In
      selected cases FXIII-A was investigated on slides prepared from blasts and
      visualized with a fluorescent microscope. In addition, blasts were studied by
      Western blot analysis and FXIII-A was measured by a highly sensitive ELISA
      method. By flow cytometry 19 samples of the 47 cases were found to be FXIII-A
      positive. Antigen concentration was 3.11 +/- 1.19 fg/blast, while normal lymphoid
      precursors and mature lymphocytes from B-CLL did not contain FXIII-A. In the
      lysate of lymphoblasts that were positive by flow cytometry, a single band (82
      kDa) corresponding to FXIII-A was detected on Western blots. Confocal laser
      scanning microscopic examination revealed the presence of FXIII-A in the
      cytoplasm of these lymphoblasts. This novel expression site of FXIII-A in
      leukemic lymphoblasts can be utilized as a diagnostic tool and may also gain
      functional significance in B-lineage ALL.

PMID- 16894462
TI  - Fibronectin binding proteins contribute to the adherence of Staphylococcus aureus
      to intact endothelium in vivo.
AB  - Staphylococcal adhesins mediate attachment to matrix proteins and endothelial
      cells in vitro, yet, their role in primary adherence to the physiologic vessel
      wall has not been studied in vivo, and complex endocarditis models yielded
      ambiguous results. Recently, we developed a hamster model to study interaction
      kinetics of S. aureus with intact microvasculature using intravital fluorescence
      microscopy (Laschke et al. J Infect Dis 2005; 191: 435-443) providing the basis
      for this study. S. aureus Cowan 1 wild type (WT) log phase cells adhered to
      postcapillary venules to a significantly larger extent compared to stationary
      phase staphylococci, a finding in congruence with the fact that the
      staphylococcal adhesin repertoire largely depends on the growth phase. In
      comparison, the adherence rate of the fnbA deleted mutant (DU5895) to the vessel
      wall was significantly reduced to approximately 40% of WT. These DU5895
      attachment rates were similar to those of an S. carnosus strain (TM300). In
      contrast, upon heterologous complementation of TM300 with either fnbA and fnbB,
      adherence of these transformants to the microvasculature increased, an increase
      found to be significant for fnbA transformant single cocci and clusters at 30 and
      60 min when compared to S. carnosus TM300 WT. In conclusion, these results
      demonstrate that staphylococcal FnBPs significantly contribute to primary
      interaction with intact endothelium under physiologic conditions. Accordingly,
      this attribution of staphylococcal FnBPs provide a rationale for novel
      intervention strategies such as the use of anti-FnBP antibodies in endovascular
      S. aureus disease.

PMID- 16894463
TI  - Incidence and predictors of subacute thrombosis in patients undergoing primary
      angioplasty for an acute myocardial infarction.
AB  - Subacute thrombosis (SAT) is a major concern in patients undergoing percutaneous
      coronary intervention (PCI). So far, only little data has been available on
      characteristics and outcome of patients with SAT after primary PCI for ST
      elevation myocardial infarction (STEMI). From 1997-2001, 1,548 unselected
      consecutive patients underwent primary PCI for STEMI as part of a randomized
      controlled trial stenting vs. balloon angioplasty. All patients received
      acetylsalicylic acid (500 mg i.v.) and heparin (5,000 IU) before the procedure.
      After stenting, all patients received ticlopidine 250 mg daily (before July 1999)
      or clopidogrel 75 mg daily (after July 1999) for one month. Five percent of
      patients received glycoprotein IIb/IIIa blockers. We prospectively recorded
      incidence and characteristics of patients with SAT during one year follow-up. SAT
      occurred in 4.1% (63/1548) and reinfarction in 6.0% of patients. The incidence of
      SAT did not change over time (1997: 8/175[4.6%],1998: 8/325 [2.5%],1999: 13/358
      [3.6%], 2000: 22/426 [5.2%], 2001: 12/264 [4.5%]). SAT occurred in 39/63(62%)
      patients during hospital stay. The incidence did not differ between patients
      after ticlopidine 23/681 (3.4%) or clopidogrel 40/867 (4.6%, p = 0.222).
      Univariate predictors of SAT were: patients with an LAD stenosis (5.4% vs. 2.9%,
      p = 0.016), with Killip class >1 at presentation (8.6% vs. 3.7%, p = 0.007) and
      in patients who received a stent (5.1% vs. 2.7%, p = 0.022). After multivariate
      analysis, Killip class >1 on admission was the only independent predictor of
      SAT(OR 2.26, 95% CI 1.14-4.47, p = 0.019). SAT was associated with a higher
      mortality at long-term follow-up (15% vs. 7%, p = 0.026). In a prospectively
      recorded, unselected consecutive series of patients undergoing PCI for STEMI, SAT
      occurred in 4.1% of patients at one-year follow-up. Signs of heart failure on
      admission, anterior myocardial infarction and stenting were predictors of SAT.

PMID- 16894464
TI  - Formation of tissue factor-factor VIIa-factor Xa complex prevents apoptosis in
      human breast cancer cells.
AB  - Tissue factor (TF) is a transmembrane glycoprotein that initiates blood
      coagulation when complexed with factor VIIa (FVIIa). TF is constitutively
      expressed in a variety of tumor cells and has been shown to play a role in
      cellular signaling and tumor progression. In this study, we investigated the
      effect of TF-FVIIa mediated signaling on apoptosis in human breast cancer cells.
      Apoptosis was induced by prolonged serum starvation and studied using the Adr-MCF
      7 cell line, which has high endogenous TF expression. Treatment of the cells with
      the combination of FVIIa (10 nM) and FX (150 nM), reduced apoptosis by nearly 50%
      compared with untreated, control cells using an ELISA that detects histone-DNA
      fragments. In contrast, FVIIa (10 nM) alone did not significantly prevent
      apoptosis. Pretreatment of the Adr-MCF-7 cells with hirudin, a specific thrombin
      inhibitor, did not inhibit the anti-apoptotic effect of the combination of FVIIa
      and FX, whereas this effect could be abrogated by inhibition of phosphorylation
      of either p44/42 mitogen-activated protein kinase (MAPK) or protein kinase B
      (PKB/Akt). In addition, treatment of the Adr-MCF-7 cells with the combination of
      FVIIa and FX led to a 30-50% increase in the level of the anti-apoptotic protein,
      survivin, compared with untreated cells using Western blot analysis. These
      results indicate that formation of TF-FVIIa-FXa complex prevents apoptosis in
      breast cancer cells by a thrombin-independent pathway. Moreover, the anti
      apoptotic effect of this signaling pathway involves phosphorylation of both
      p44/42 MAPK and PKB/Akt and might be mediated in part by an increase in cell
      survivin levels.

PMID- 16894465
TI  - Platelet activation and high tissue factor level predict acute stent thrombosis
      in pig coronary arteries: prothrombogenic response of drug-eluting or bare stent
      implantation within the first 24 hours.
AB  - Increased thrombogenicity of drug-eluting stents (DESs) has recently been
      reported. The aim of the present study was to investigate the prothrombogenic
      effect of DESs and Bare stents, and determine factors predictive of acute stent
      thrombosis (AST) in preclinical experiments using new stent design or coating.
      Circulating pre- and post-stenting parameters of platelet activation (mean
      platelet volume, MPV; platelet distribution width, platelet large cell ratio),
      thrombin activation (thrombin-antithrombin complex, TAT and prothrombin
      fragments, F1+2), tissue factor antigen (TF-ag) and -activity (TF-act) and
      plasminogen activator inhibitor-1 (PAI-1) were measured in 141 consecutive pigs.
      Stent implantations were performed after pretreatment with aspirin and
      clopidogrel with unfractionated heparin anticoagulation. Nineteen pigs (groups
      AST-DES, n = 12; and AST-Bare, n = 7) died mean 6.3 +/- 2.9 h after stent
      implantation from AST. The remaining 122 control (C) pigs (groups C-DES, n = 76,
      and C-Bare, n = 46) survived the 1-month follow-up. Non-significantly elevated
      levels of post-stent F1+2 and TAT were measured in AST groups. Post-stenting MPV
      was increased significantly in the groups ASTDES and AST-Bare as compared with
      the groups C-DES and C-Bare (11.73 +/- 1.12 and 11.6 +/- 0.68 vs. 8.85 +/- 0.78
      and 9.04 +/- 0.81 fL; p < 0.001), similarly to TF-ag (189.1 +/- 87.5 and 127 +/-
      34.9 vs. 42.5 +/- 24.6 and 35.3 +/- 37.6 pg/ml; p < 0.001, respectively), Tfact
      (3.23 +/- 0.95 and 2.73 +/- 1.68 vs. 1.43 +/- 1.12 and 1.61 +/- 1.31 pM; p <
      0.01, respectively) and PAI-1 (99.1 +/- 15.8 and 99 +/- 14.7 vs.53.4 +/- 40.2 and
      46.9 +/- 42.4 ng/ml;p < 0.01, respectively). Multivariate analysis revealed
      elevated post-stenting plasma levels of TF-ag (p = 0.016) and MPV (p = 0.001) as
      independent risk factors for developing AST within the first 24 h in a porcine
      coronary stent model.

PMID- 16894466
TI  - Long-term stability of relationships between reference materials for
      thromboplastins.
AB  - Reference materials for thromboplastins are available from the World Health
      Organization (WHO) and the European Commission (EC). The long-term stability of
      the reference materials is an essential requirement and must be monitored. The
      relationship between two reference materials for rabbit thromboplastin, i.e. ERM
      AD149 (EC) and RBT/90 (WHO), has been monitored in the period 1996-2002. No
      significant trend with time was detected. In addition, the relationship between
      ERM-AD149 and the reference material for bovine thromboplastin (i.e. OBT/79) has
      been determined in 1994 and in 2005 in multicentre studies (n = 11 and n = 9,
      respectively). No significant changes were observed in the relationships between
      these reference materials when all results were included (5% significance level).

PMID- 16894467
TI  - Establishment of the 1st International Genetic Reference Panel for Factor V
      Leiden, human gDNA.
AB  - Forty-one laboratories participated in an international collaborative study to
      assess the suitability of a panel of three genomic DNA samples as the 1st
      International Genetic Reference Panel for the Factor V Leiden (FVL) variant. The
      code numbers of the materials were 03/254 (FV wild type), 03/260 (FVL homozygote)
      and 03/248 (FVL heterozygote). The participants evaluated the panel against their
      in-house controls which were known patient samples and commercial controls. In
      total, 859 genotype tests were carried out on the panel, with an error rate of
      0.7%. The errors were not related to specific samples of the panel or to any
      specific techniques. The findings of this study have indicated that this panel is
      suitable to be used as a reference material for genotyping of factor V Leiden. It
      was therefore recommended that the three genomic DNA samples be established as
      the 1st International Genetic Reference Panel for Factor V Leiden, Human gDNA,
      04/224. This recommendation was approved by the Scientific and Standardization
      Committee (SSC) of the ISTH (International Society on Thrombosis and Haemostasis)
      in June 2004 and the Expert Committee on Biological Standardization (ECBS) of the
      World Health Organization (WHO) in November 2004.

PMID- 16894468
TI  - Assessment of genetic risk for myocardial infarction.
AB  - Although lifestyle and environmental factors influence the prevalence of
      myocardial infarction, genetic epidemiological studies have suggested that
      several genetic variants increase the risk for this condition. We have performed
      a large-scale association study to identify gene polymorphisms for reliable
      assessment of the genetic risk of myocardial infarction. The study population
      comprised 3,483 unrelated Japanese individuals (1,913 men; 1,570 women),
      including 1,192 subjects with myocardial infarction and 2,291 controls. The
      genotypes for 164 polymorphisms of 137 candidate genes were determined with an
      oligonucleotide ligation assay based on analysis of fluorescent microspheres with
      suspension array technology. Multivariable logistic regression analysis with
      adjustment for age, sex, body mass index, and the prevalence of smoking,
      hypertension, diabetes mellitus, and hypercholesterolemia revealed that the 677C-
      >T (Ala222Val) polymorphism of MTHFR, the 1595C-->G (Ser447Stop) polymorphism of
      LPL, and the -108/3G-->4G polymorphism of IPF1 were significantly associated with
      the prevalence of myocardial infarction. A stepwise forward selection procedure
      demonstrated that IPF1, MTHFR, and LPL genotypes significantly affected the
      prevalence of myocardial infarction. Combined genotype analysis of these
      polymorphisms yielded a maximum odds ratio of 2.54 for the combined genotype of
      TT for MTHFR, CC for LPL, and 3G3G for IPF1. The genotypes for MTHFR, LPL, and
      IPF1 may prove reliable for assessment of genetic risk for myocardial infarction.
      Determination of the combined genotype for these genes may contribute to primary,
      personalized prevention of this condition.

PMID- 16894469
TI  - R924Q substitution encoded within exon 21 of the von Willebrand factor gene
      related to mild bleeding phenotype.

PMID- 16894470
TI  - Fibrinogen Montreal: a novel missense mutation (Aa D496N) associated with
      hypofibrinogenaemia.

PMID- 16894471
TI  - Hyperhomocysteinaemia, thrombosis and pernicious anaemia.

PMID- 16894472
TI  - TAFI activity in coronary artery disease: a contribution to the current
      discussion on TAFI assays.

PMID- 16894474
TI  - Design of a novel plasminogen activator based on the structure of hirudin.
AB  - Using a phage library, seven peptide sequences with high affinity to human
      microplasminogen were obtained. Caseinolytic assay indicated that only the
      synthesized peptide P07 had slight fibrinolytic activity. To enhance its
      plasminogen activation ability, peptide P07 was fused into loop 32-35 of hirudin.
      In vitro assay demonstrated that this hirudin-like fusion protein can activate
      human plasminogen and retain the function of thrombin inhibition. Fusing the
      sequence ''SPDASRL'' into hirudin generated a plasminogen activation activity 100
      times higher than peptide P07 in chromogenic and radial caseinolytic assay. This
      significant functional improvement might originate from a more specific active
      structure due to the hirudin scaffold.

PMID- 16894473
TI  - Integrin beta(1A) upregulates p27 protein amount at the post-translational level
      in human hepatocellular carcinoma cell line SMMC-7721.
AB  - Integrins mediate many fundamental cellular processes by binding to components of
      the extracellular matrix. We showed previously that integrin beta(1A) could
      inhibit cell proliferation. Integrin beta(1A) stimulated the promoter activity of
      p21(cip1) and enhanced its transcription in SMMC-7721 cells. In this study, we
      demonstrated that integrin beta(1A) upregulated p27(kip1) at the post
      translational level in SMMC-7721 cells. Our results showed that integrin beta(1A)
      increased the p27 protein amount, both in cytoplasm and nucleus, but did not
      affect the p27 mRNA amount. Cycloheximide treatment experiment revealed that the
      half-life of p27 protein was prolonged in integrin beta1A overexpressing cells,
      indicating that integrin beta(1A) inhibited the degradation of p27 protein. Our
      data also provided evidence that both the proteasome and calpain were involved in
      the degradation of p27 protein in SMMC-7721 cells. Integrin beta(1A) decreased
      the Skp2 expression and repressed the activity of calpain during G1 phase in SMMC
      7721 cells. Taken together, these results indicated that integrin beta(1A) might
      upregulate the protein amount of p27 through repressing Skp2-dependent proteasome
      degradation and calpain-mediated proteolysis in SMMC-7721 cells.

PMID- 16894475
TI  - B22 Glu des-B30 insulin: a novel monomeric insulin.
AB  - Studies on monomeric insulin with reduced self-association are important in the
      development of insulin pharmaceutical preparations with rapid hypoglycemic action
      on patients with diabetes. Here we report a novel monomeric insulin, B22 Glu des
      B30 insulin, prepared from a single chain insulin precursor with B22 Arg mutated
      to Glu, which was expressed in Pichia pastoris and converted to B22 Glu des-B30
      insulin by tryptic digestion. It still retains 50% of the in vivo biological
      activity of porcine insulin and does not form a dimer even at a concentration of
      10 mg/ml, showing that B22 Glu plays a key role in reducing the self-association
      of the insulin molecule without greatly reducing its biological activity. This
      novel monomeric insulin might have potential applications in the clinic.

PMID- 16894476
TI  - Isolation of a cDNA encoding a protease from Perinereis aibuhitensis Grube.
AB  - The cDNA encoding a protease of Perinereis aibuhitensis Grube (PPA) was cloned.
      The deduced amino acid sequence analysis showed that the protein had 49% identity
      to the C-terminal amino acid 169-246 of serine protease of Heterodera glycines.
      Northern blotting analysis indicated that the cDNA could hybridize with mRNA of
      approximately 260 bases isolated from the marine earthworm. The cDNA was
      amplified by polymerase chain reaction and cloned into pMAL-p2 to construct
      expression vector pMAL-PPA. pMAL-PPA was introduced into Escherichia coli
      BL21(DE3) and overexpression of PPA fused with maltose binding protein was
      achieved by isopropyl-beta-D-thiogalactopyranoside induction. The fusion protein
      was purified by affinity chromatography on an amylose resin column and ion
      exchange chromatography on a diethylaminoethyl-Sepharose 4B column. Rabbits were
      immunized with the purified protein and antiserum was prepared. The antibody
      could react with a protein of approximately 9 kDa extracted from the marine
      earthworm as shown by Western blotting analysis. The activity analysis of the
      recombinant PPA suggested that it was probably a plasminogen activator.

PMID- 16894477
TI  - Verification, characterization and tissue-specific expression of UreG, a urease
      accessory protein gene, from the amphioxus Branchiostoma belcheri.
AB  - UreG genes have been found in bacteria, fungi and plants but have not yet
      identified in animals, although a putative UreG-like gene has been documented in
      sea urchin. In the course of a large-scale sequencing of amphioxus gut cDNA
      library, we have identified a cDNA with high similarity to UreG genes. Both
      reverse transcription-polymerase chain reaction and nested polymerase chain
      reaction, as well as in situ hybridization histochemistry, verified that the cDNA
      represented an amphioxus UreG gene (AmphiUreG) rather than a microbial
      contaminant of the cDNA library. This is further supported by the presence of
      urease activity in amphioxus gut, gill and ovary. AmphiUreG encodes a deduced
      protein of 200 amino acid residues including a highly conserved P-loop, bearing
      approximately 46%-49%, 44%-48%, and 29%-37% similarity to fungal, plant and
      bacterial UreG proteins, respectively. It shows a tissue-specific expression
      pattern in amphioxus, and is especially abundant in the digestive system. This is
      the first UreG gene identified in animal species.

PMID- 16894478
TI  - Increased association of dynamin II with myosin II in ras transformed NIH3T3
      cells.
AB  - Dynamin has been implicated in the formation of nascent vesicles through both
      endocytic and secretory pathways. However, dynamin has recently been implicated
      in altering the cell membrane shape during cell migration associated with
      cytoskeleton-related proteins. Myosin II has been implicated in maintaining cell
      morphology and in cellular movement. Therefore, reciprocal immunoprecipitation
      was carried out to identify the potential relationship between dynamin II and
      myosin II. The dynamin II expression level was higher when co-expressed with
      myosin II in Ras transformed NIH3T3 cells than in normal NIH3T3 cells. Confocal
      microscopy also confirmed the interaction between these two proteins.
      Interestingly, exposing the NIH3T3 cells to platelet-derived growth factor
      altered the interaction and localization of these two proteins. The platelet
      derived growth factor treatment induced lamellipodia and cell migration, and
      dynamin II interacted with myosin II. Grb2, a 24 kDa adaptor protein and an
      essential element of the Ras signaling pathway, was found to be associated with
      dynamin II and myosin II gene expression in the Ras transformed NIH3T3 cells.
      These results suggest that dynamin II acts as an intermediate messenger in the
      Ras signal transduction pathway leading to membrane ruffling and cell migration.

PMID- 16894479
TI  - beta-Glucosidase catalyzing specific hydrolysis of an iridoid beta-glucoside from
      Plumeria obtusa.
AB  - An iridoid beta-glucoside, namely plumieride coumarate glucoside, was isolated
      from the Plumeria obtusa (white frangipani) flower. A beta-glucosidase, purified
      to homogeneity from P. obtusa, could hydrolyze plumieride coumarate glucoside to
      its corresponding 13-O-coumarylplumieride. Plumeria beta-glucosidase is a
      monomeric glycoprotein with a molecular weight of 60.6 kDa and an isoelectric
      point of 4.90. The purified beta-glucosidase had an optimum pH of 5.5 for p
      nitrophenol (pNP)-beta-D-glucoside and for its natural substrate. The Km values
      for pNP-beta-D-glucoside and Plumeria beta-glucoside were 5.04+/-0.36 mM and
      1.02+/-0.06 mM, respectively. The enzyme had higher hydrolytic activity towards
      pNP-beta-D-fucoside than pNP-beta-D-glucoside. No activity was found for other
      pNP-glycosides. Interestingly, the enzyme showed a high specificity for the
      glucosyl group attached to the C-7' position of the coumaryl moiety of plumieride
      coumarate glucoside. The enzyme showed poor hydrolysis of 4-methylumbelliferyl
      beta-glucoside and esculin, and did not hydrolyze alkyl-beta-glucosides,
      glucobioses, cyanogenic-beta-glucosides, steroid beta-glucosides, nor other
      iridoid beta-glucosides. In conclusion, the Plumeria beta-glucosidase shows high
      specificity for its natural substrate, plumieride coumarate glucoside.

PMID- 16894480
TI  - Optimized adaptor polymerase chain reaction method for efficient genomic walking.
AB  - Genomic walking is one of the most useful approaches in genome-related research.
      Three kinds of PCR-based methods are available for this purpose. However, none of
      them has been generally applied because they are either insensitive or
      inefficient. Here we present an efficient PCR protocol, an optimized adaptor PCR
      method for genomic walking. Using a combination of a touchdown PCR program and a
      special adaptor, the optimized adaptor PCR protocol achieves high sensitivity
      with low background noise. By applying this protocol, the insertion sites of a
      gene trap mouse line and two gene promoters from the incompletely sequenced
      Xenopus laevis genome were successfully identified with high efficiency. The
      general application of this protocol in genomic walking was promising.

PMID- 16894481
TI  - Disruption effect of Microplitis bicoloratus polydnavirus EGF-like protein,
      MbCRP, on actin cytoskeleton in lepidopteran insect hemocytes.
AB  - Microplitis bicoloratus is a braconid endoparasitic wasp associated with the
      polydnavirus named Microplitis bicoloratus bracovirus (MbBV). Parasitism of
      Spodoptera litura larvae leads to an impaired cellular immune response and to the
      disappearance of the 42 kDa actin in host hemocytes. In this work, we
      investigated if the absence of actin in blood cells was related to MbBV
      infection. An MbBV gene similar to egf-like genes identified in another
      bracovirus was partially cloned and named Mbcrp1. The full-length gene, named
      Mbcrp, is transcribed throughout the course of parasitism in host hemocytes and
      the 30 kDa MbCRP protein was detected in hemocytes 6-7 d post-parasitization. The
      Mbcrp1 gene contains the cysteine-rich trypsin inhibitor-like (TIL) domain coding
      sequence and the expression of recombinant MbCRP1 inhibited the expression of the
      42 kDa actin in Hi5 cells. The 34.1 kDa MbCRP1-green fluorescent protein fusion
      protein locate specifically in the cytoplasm. These results suggest that
      expression of MbCRP in lepidopteran insect cells is related to the disruption of
      the actin cytoskeleton.

PMID- 16894482
TI  - Human proinsulin C-peptide from a precursor overexpressed in Pichia pastoris.
AB  - In this article we report the production of human proinsulin C-peptide with 31
      amino acid residues from a precursor overexpressed in Pichia pastoris. A C
      peptide precursor expression plasmid containing nine C-peptide genes in tandem
      was constructed and used to transform P. pastoris. Transformants with a high copy
      number of the C-peptide precursor gene integrated into the chromosome of P.
      pastoris were selected. In high-density fermentation in a 300 liter fermentor
      using a simple culture medium composed mainly of salt and methanol, the C-peptide
      precursor was overexpressed to a level of 2.28 g per liter. A simple procedure
      was established to purify the expression product from the culture medium. The
      purified C-peptide precursor was converted into C-peptide by trypsin and
      carboxypeptidase B joint digestion. The yield of C-peptide with a purity of 96%
      was 730 mg per liter of culture. The purified C-peptide was characterized by mass
      spectrometry, N- and C-terminal amino acid sequencing, and sodium dodecylsulfate
      polyacrylamide gel electrophoresis.

PMID- 16894483
TI  - Coronal-posterior approach for face/scalp flap harvesting in preparation for face
      transplantation.
AB  - This report describes the development of a new technique for harvesting facial
      allograft for facial transplantation. The coronal-posterior surgical approach for
      facial/scalp flap harvesting from donor cadavers has been developed to allow
      extended length to the neurovascular bundles utilized in facial composite
      allograft transplantation. Cadaveric anatomic dissections were performed to
      harvest facial/scalp flaps via a posterior-coronal approach. Supraorbital and
      infraorbital neurovascular bundle lengths were extended by osteotomy of the
      cranial/orbital bone. The mental nerve lengths were extended into the inferior
      alveolar neurovascular bundle utilizing a sagittal split ramus osteotomy. This
      surgical approach extends the length of these craniofacial nerves for future
      neurorrhaphy. The mean length of the supraorbital, infraorbital, and mental
      nerves was 3.52 +/- 0.31 cm, 4.65 +/- 0.20 cm, 5.6 +/- 0.14 cm, respectively.
      Based on anatomical dissection in this cadaver study, the authors introduce a new
      technique for facial/scalp flap harvesting that extends the neurovascular bundles
      of sensory nerves of the anterior craniofacial skeleton.

PMID- 16894484
TI  - Results of replantation of amputated fingertips in 450 patients.
AB  - Over a 15-year period (August, 1988 to May 2003), the authors have carried out
      510 replantations of amputated fingertips distal to the nail base (zone I) in 450
      patients, with a high overall survival rate (92 percent), using combinations of
      arterial and venous anastomoses without any alternative methods such as
      "pocketing." Replantations that anastomosed only one artery (25 digits) had a
      success rate of 68 percent, one artery and one vein (115 digits) had a success
      rate of 82 percent, one artery and two veins (240 digits) had a success rate of
      95 percent and more than two artery and vein anastomoses (130 digits), had a
      success rate of 99 percent. The follow-up period ranged from 3 months to 14 years
      and 432 patients were followed-up more than 6 months. In these latter patients,
      the average two-point discrimination was 7 mm.

PMID- 16894485
TI  - Limb salvage in proximal humerus malignant tumors: the place of free vascularized
      fibular graft.
AB  - Limb-salvage surgery has become a safe and well-established alternative to
      amputations for malignant tumors of the proximal humerus. The authors describe
      six cases with favorable restoration of the upper limb following tumor resection
      type IB Malawer and proximal humeral reconstruction by vascularized fibula graft
      (VFG) as a primary or secondary procedure. A scapulofibular arthrodesis was
      elected in all cases. A special custom-made plate was used in four cases. One
      patient required a latissimus dorsi musculocutaneous flap for better coverage.
      Serial x-rays assessed the bone union. Neither flap necrosis nor sepsis phenomena
      were noted. Stress fracture was the only complication. This was encountered in
      two cases. Every patient was reviewed and assessed by the Enneking score. The
      average score was 21.8. The average follow-up was 5-years. A good quality of life
      was preserved due to reliable mobility of the elbow and the hand.

PMID- 16894486
TI  - Ultrasonographic evaluation of functioning free muscle transfer: comparison
      between spinal accessory and intercostal nerve reinnervation.
AB  - This study focuses on the application of ultrasonography as a means of measuring
      the cross-sectional area (CSA) of the transferred muscle and evaluating its force
      recovery following functioning free muscle transfer. The objective of the study
      was to compare the CSA of a transferred muscle that is either reinnervated by the
      spinal accessory nerve (SAN) or the intercostal nerve (ICN), and to evaluate the
      difference in their force recovery. Ten patients with complete avulsion of the
      brachial plexus who underwent a double free muscle technique for restoring
      prehensile function were evaluated. All patients were followed up for at least
      1.5 years after the operation. The CSAs of 20 transferred gracilis muscles in 10
      patients, reinnervated either by SAN or ICN, were measured by ultrasonography.
      The CSA was measured at relaxation and at maximal isometric contraction. The
      force recovery of each muscle was expressed as the contraction rate (CR),
      calculated by dividing the CSA of the muscle in maximum isometric contraction by
      the CSA of the muscle in relaxation. The mean CSA of the transferred muscles
      reinnervated by the SAN was 2.98 +/- 0.723 cm (2) in relaxation and 3.95 +/-
      1.296 cm (2) in maximum isometric contraction; thereby a CR of 1.32 +/- 0.174 was
      obtained. The mean CSA of the transferred muscles reinnervated by the ICN was
      2.32 +/- 0.520 cm (2) and 2.69 +/- 0.566 cm (2) in relaxation and maximal
      isometric contraction, respectively; thus a CR of 1.16 +/- 0.068 was obtained.
      Results showed that the CR was significantly higher among the transferred muscles
      reinnervated by the SAN than those by the ICN. This study demonstrated that
      muscles that are reinnervated by the SAN resulted in stronger recovery than those
      reinnervated by the ICN, and that ultrasonography has the capacity to evaluate
      force recovery of each muscle by measuring the CSA during the two phases of
      muscle activity.

PMID- 16894487
TI  - Feasibility of robotic-assisted microvascular anastomoses in plastic surgery.
AB  - In this pilot trial in piglets, the authors demonstrated the feasibility of
      applying robot technology to vascular microsurgery. This preliminary work
      suggests certain advantages of the robot, which should encourage more rigorous
      study for its full exploitation.

PMID- 16894488
TI  - Innervated free flaps for foot reconstruction: a review.
AB  - Whether to provide a sensate plantar weight-bearing flap to reconstruct the foot
      remains an unanswered, but frequently asked, question. It has been more than a
      decade since Graham and Dellon reviewed this subject. Increasing emphasis on
      outcome analysis of microsurgical reconstruction has prompted this new review.
      All published peer-reviewed literature related to reconstruction of the plantar
      surface of the foot was reviewed to identify whether the flaps were 1) local,
      regional or distant; 2) innervated or non-innervated and, if innervated, then 3)
      identified as to the donor and the recipient peripheral nerves. Outcome measures
      included direct measurement of sensibility, development of ulceration, and
      activities of daily living. It was concluded that it is still not possible to
      determine that innervated flap reconstruction of the weight-bearing portion of
      the foot is critical for either durability or ambulation. It is recommended that
      the original nerves that innervate the flap be blocked prior to harvest to
      improve flap design, i.e., that the flap actually contains the intended nerve. It
      is recommended that appropriate donor nerves are selected to innervate the flaps,
      e.g., the calcaneal nerve should be used to reinnervate heel reconstructions
      (rather than the sural nerve), and medial/lateral plantar branches be used to
      reinnervate the arch and the forefoot. Reinnervating a muscle flap with a sensory
      nerve will permit reinnervation of the muscle and the overlying skin, but whether
      this provides a superior result in durability and gait remains to be seen.

PMID- 16894489
TI  - Survival of long nerve allografts following donor antigen pretreatment: a pilot
      study.
AB  - In this study, the authors evaluated whether the pretransplant portal venous
      administration of UV-B irradiated donor alloantigen would induce tolerance to
      long peripheral nerve allografts in a swine model. They completed nerve allograft
      transplantation between four swine of separate lineages. Regeneration across the
      nerve allografts was followed for 10 months postoperatively. Sequential IN VITRO
      assays demonstrated the successful and prolonged suppression of the recipient
      immune response to donor antigen following antigen inoculation. Histomorphometric
      analysis demonstrated successful regeneration across the long nerve allografts in
      the pretreated recipients, but not across allografts in unimmunosuppressed
      recipients. A single pretransplant antigen delivery protocol has the potential to
      replace chronic medicinal immunosuppressant therapy and its associated
      morbidities. Furthermore, tolerance to long nerve allografts has immediate
      applicability to clinical requirements for bridging multiple, complex, long nerve
      gaps.

PMID- 16894490
TI  - Subtotal nasal reconstruction for ethmoid sinus cancer defect using a fibula
      osteocutaneous free flap.

PMID- 16894491
TI  - Monitoring the surgeon, not the free flap.

PMID- 16894492
TI  - [On free will].

PMID- 16894493
TI  - [Neurobiological determinism: questionable inferences on human freedom of choice
      and forensic criminal responsibility].
AB  - Several authors argue that criminal behavior is generally caused by
      neurobiological deficits. Based on this neurobiological perspective of assumed
      causality, the concept of free will is questioned, and the theory of
      neurobiological determinism of all human behavior is put forward, thus
      maintaining that human beings are not responsible for their actions, and
      consequently the principle of guilt should be given up in criminal law. In this
      context the controversial debate on determinism and indeterminism, which has been
      held for centuries, has flared up anew, especially within the science of criminal
      law. When critically examining the current state of research, it becomes apparent
      that the results do not support the existence of a universally valid
      neurobiological causality of criminal behavior, nor a theory of an absolute
      neurobiological determinism. Neither is complete determination of all phenomena
      in the universe--as maintained--the logical conclusion of the principle of
      causality, nor is it empirically confirmed. Analyzed methodically, it cannot be
      falsified, and thus, as a theory which cannot be empirically tested, it
      represents a dogma against which plausible objections can be made. The criticism
      of the concept of free will, and even more so of human accountability and
      criminal responsibility, is not put forward in a valid way. The principle of
      relative determinism--the evaluation of the degree of determinism of personality
      factors potentially reducing criminal responsibility, which includes concrete
      observations and analysis of behavior--thus remains a central and cogent approach
      to the assessment of criminal responsibility. To sum up, the theories proposed by
      some authors on the complete neurobiological determinism of human behavior, and
      the subsequent impossibility of individual responsibility and guilt, reveal both
      methodical misconception and a lack of empirical foundation.

PMID- 16894494
TI  - [Can neurological soft signs (NSS) contribute to the prediction of dangerousness
      in mentally disordered offenders?].
AB  - The prediction of dangerousness in mentally disordered offenders is still as well
      complex as insufficiently empirically proven. So far more or less valid criteria
      for predicting recidivism have been determined concerning historical and clinical
      aspects. Whereas biological, neurological and neuropsychological variables that
      could be of importance for the development of chronic delinquent behavior have
      mostly been neglected. This article deals with the relevance of neurological soft
      signs (NSS) for the prediction of dangerousness in mentally ill offenders as one
      possible factor in a multidimensional model. 155 patients were examined after a
      minimum time at risk of 2 years (mean 4 years). The results showed that on the
      one hand there is no relevant and valid connection between neurological soft
      signs and recidivism for the general heterogeneous group of forensic patients. On
      the other hand similar results arose for the subgroup of patients with a
      personality disorder without intellectual deficits as for the homogeneous group
      of offenders in prisons. Therefore a significant meaning of NSS for certain
      subgroups can be presumed.

PMID- 16894495
TI  - [Intelligence deficits].

PMID- 16894496
TI  - [Radiofrequency ablation of lung tumors].
AB  - Radiofrequency (RF) ablation is an effective therapy option in the treatment of
      primary and secondary liver tumors. Percutaneous RF ablation of primary and
      secondary pulmonary tumors is a possible new indication. Due to the minimally
      invasive character of percutaneous RF ablation, application in patients who are
      not candidates for curative radical resection is possible. Moreover, pulmonary RF
      ablation is a promising palliative therapy option. In this context, an increasing
      number of results regarding RF ablation of lung tumors were recently published.
      The present review summarizes and discusses the possible indications, techniques,
      results, and complications of pulmonary RF ablation.

PMID- 16894497
TI  - [Influence of body mass index on coronary artery opacification in 64-slice CT
      angiography].
AB  - PURPOSE: To evaluate the influence of the body mass index (BMI) on coronary
      artery opacification in 64-slice CT. MATERIAL AND METHODS: Sixty-two patients
      retrospectively underwent ECG-gated 64-slice CT coronary angiography (tube
      potential 120 kV, tube current time product 650 mAs) after intravenous injection
      of 80 ml of iodinated contrast agent (320 mg/ml, 5 ml/s). Attenuation values (HU)
      were measured and contrast-to-noise ratios (CNR) were calculated in the right
      coronary artery (RCA) and left main artery (LMA). The CNR was defined as the
      difference between the mean attenuation in the vessel and the mean attenuation in
      the perivascular fat tissue divided by the image noise in the ascending aorta.
      The height and weight of the patients at the time of the CT scan were recorded
      and the BMI was calculated. RESULTS: The mean BMI was 26.2 +/- 3.2 kg/m (2)
      (range 19.7 - 32.2 kg/m (2)), the mean attenuation in the LMA was 330 +/- 64 HU,
      and the mean attenuation in the RCA was 309 +/- 68 HU. The CNR in the LMA was
      16.7 +/- 3.8, and the CNR in the RCA was 15.9 +/- 3.6. The image noise in the
      ascending aorta significantly correlated with the BMI (r = 0.36, p < 0.01). A
      weak negative correlation was found between the BMI and LMA attenuation (r = -
      0.28, p < 0.05), whereas no significant correlation was found for the RCA (r = -
      0.21, p = 0.12). A significant negative correlation was found between the BMI and
      the CNR in the RCA (r = - 0.41, p < 0.05) and the LMA (r = - 0.47, p < 0.001).
      CONCLUSION: With constant scan parameters and a constant contrast medium amount,
      the CNR in both coronary arteries decreases while the BMI increases. This implies
      a modification of previously standardized and fixed examinations with respect to
      individually adapted protocols with variable parameters for CT coronary
      angiography.

PMID- 16894498
TI  - [Incidence of major amputations, bypass procedures and percutaneous transluminal
      angioplasties (PTA) in the treatment of peripheral arterial occlusive disease in
      a German referral center 1996-2003].
AB  - PURPOSE: To determine the current incidence of major amputations, bypass
      procedures and percutaneous transluminal angioplasties (PTA) in a study
      population of patients with peripheral arterial occlusive disease in a German
      referral center. MATERIALS AND METHODS: In a retrospective study, we recruited
      patients with peripheral arterial occlusive disease who underwent an amputation,
      bypass procedure, or PTA in the region of the pelvis or lower limbs between 1996
      and 2003 at the Augsburg Medical Center. Patients were identified via the
      hospital database. This was performed with the help of the International
      Classification of Diseases (ICD 9 and 10), the operation code (OPS), and
      appropriate invoices. The incidence of PTAs was further estimated with 200
      charts. RESULTS: Of 5379 patients, 627 underwent amputation, 1832 a bypass
      procedure, and 2920 a PTA. The incidence of PTAs increased during the study
      period from 51.3/100 000/year to 64.4/100 000/year (p < 0.01), while the number
      of amputations and bypass procedures remained stable. The incidence of PTAs was
      exceeded by that of bypass procedures only in patients older than 85 years. The
      age of the amputees decreased during the study period from 72.2 to 70.5 years (p
      < 0.01). The age of patients who underwent a bypass procedure increased from 67.2
      to 69.4 years, and the age of patients who underwent PTA increased from 66.3 to
      69.8 years (p < 0.01). Bypass procedures and PTAs were performed in men 6.3 years
      earlier than in women (p < 0.01). CONCLUSION: The result is a population
      corrected need of 8.4/100 000/year major amputations, 23/100 000/year bypass
      procedures and 64.4/100 000/year PTAs for patients with peripheral arterial
      occlusive disease within the referral area of our hospital. The performance of
      major amputations and bypass procedures stagnates, while the incidence of PTAs is
      increasing.

PMID- 16894499
TI  - [First results with catheter and magnetically guided and detached polymerized
      ferromagnetic particle filaments and heat-induced particle release using the
      Stereotaxis Niobe system].
AB  - PURPOSE: To develop a new technique for intravascular guidance and the release of
      magnetized ferromagnetic nanoparticles using a polymerized filament by means of
      an external magnetic field. MATERIALS AND METHODS: Ferromagnetic nanoscaled beads
      were embedded in temperature-sensitive gels to form filaments after
      polymerization. Deflection of the filaments was assessed in a Stereotaxis Niobe
      magnetic navigation system (MNS) in comparison with dedicated guide wires. The
      curvature was measured as a surrogate parameter for deflection. In combination
      with commercially available catheters, the filaments were navigated in a perfused
      aneurysmatic vessel model and a perfused branched vessel model under the
      influence of two permanent magnets of the Niobe MNS. The magnetic field vector
      was varied in all three dimensions. After positioning, the magnetic colloid
      containing filaments were exposed to an electromagnetic field of 45 kA/m, 200 kHz
      for a period of 5 minutes for non-invasive heating. RESULTS: The filaments showed
      superior deflectability compared to the dedicated guide wires (p = 0.0091). The
      curvature was 0.54 +/- 0.12 mm(-1) for the filaments and 0.33 +/- 0.21 mm(-1) for
      the guide wires. In combination with angiography catheters, magnetic guidance and
      accumulation of specially designed filaments were possible in the perfused vessel
      model. Inductive heating allowed non-invasive disintegration and releasing of the
      nanoparticles in all filaments. CONCLUSION: This feasibility study shows that
      magnetic guidance and targeting of a specially designed magnetic colloid
      containing filament and subsequent disintegration are feasible. This technique
      offers the potential for controlled local drug release.

PMID- 16894500
TI  - [Langerhans cell histiocytosis as a differential diagnosis of an osteodestructive
      lesion of the pelvis in a toddler].

PMID- 16894502
TI  - [Chronic progressive external ophthalmoplegia plus: diagnosis with muscular
      magnetic resonance tomography].

PMID- 16894501
TI  - [Primary lymphoma of the liver--a difficult differential diagnosis also with
      MRI].

PMID- 16894503
TI  - [Accidental diagnosis of hepatic epithelioid hemangioendothelioma].

PMID- 16894504
TI  - [Acute penile fracture -- a rare urologic emergency].

PMID- 16894505
TI  - [Cardiac involvement in mycosis fungoides].

PMID- 16894506
TI  - [Grey-scale texture analysis of the cervix in pregnancy].
AB  - AIM: The measurement of the length of the cervix is just a method of routine, but
      the analysis of the grey-scale texture of the cervix represents a method poorly
      evaluated to date which may have the scope of improving the prediction of
      premature birth. Before it can be used for clinical purposes, the method must be
      standardised. METHODS: 66 patients were examined endosonographically. The
      analysis was done both visually and automatically, using a commercially available
      software. Inside a ROI (region of interest), we calculated the mean of the
      histogram, and homogeneity as well as contrast of the co-occurrence matrix of the
      grey-scale values. The influence of ultrasound wave propagation as well as
      location, extension and sound angle of the ROI were examined, and the results of
      the analysis performed by man and machine were compared. Additionally, we
      compared the textures of the inner and outer cervical os as well as the anterior
      and posterior lip of the cervix. RESULTS: As homogeneity and contrast were
      significantly influenced by the propagation of ultrasound waves, we developed a
      new angle-independent parameter combining the results of the 45 degrees and the
      90 degrees calculation. Small changes in location, extension and sound angle of
      the ROI did not influence our results significantly. The texture analysis
      performed by the software was significantly better than the one performed by the
      examiner. The maximum of brightness was detected in the region of the internal
      os/anterior lip. Contrast as well as homogeneity showed significant differences
      between all parts of the cervix. CONCLUSION: The analysis of the grey-scale
      texture of the cervix can deliver clinically relevant results in the prediction
      of premature birth. The external influence on sound wave propagation as well as
      different locations inside the cervix must be taken into consideration.

PMID- 16894507
TI  - [Basics of 3D and 4D fetal echocardiography using spatial and temporal image
      correlation (STIC) software].
AB  - Spatio-temporal image correlation (STIC) is a new 3D technique allowing the
      acquisition of a volume of the beating fetal heart. It is the first reliable
      technique allowing a routine 4D fetal echocardiography. This paper reviews the
      principles of this new technique and its potential. Once a volume is acquired and
      stored, it can be rendered in different display modes. The volume information can
      be displayed as a multiplanar image (A, B, and C planes) and allows the
      visualisation of an "anyplane". The information in the volume can be used to
      reconstruct a 3D rendering of the heart according to an examiner-defined volume
      of interest. Some of these rendering modes are explained in this paper, such as
      surface rendering, minimum mode, inversion mode and glass body mode (combination
      of STIC with colour or power Doppler).

PMID- 16894508
TI  - Cervical atypical mycobacterial lymphadenitis in childhood: findings on
      sonography.
AB  - PURPOSE: To describe the sonographic appearance of cervical lymph nodes in twelve
      children with histopathologically confirmed atypical mycobacterial lymphadenitis.
      MATERIALS AND METHODS: Sonography of cervical lymph nodes was performed with a
      real-time linear scanner using a 13 MHz probe. Sonographic findings were
      retrospectively reviewed in 9 girls and 3 boys age 1.7 to 10.7 years (median age,
      3.7 years), with cervical lymphadenopathy at initial presentation. RESULTS:
      Strong echoes within the lymph nodes were found in 4 (33 %) of the children,
      corresponding to calcifications on histopathological examination. Loss of regular
      nodal shape with circumscript polypoid spread of nodal masses into the
      subcutaneous tissue was found in 6 (50 %) patients; at least 1 of these 2
      features was noted in 10 (83 %) of our 12 patients. At surgery, abscess formation
      was found in 8 (67 %) children. CONCLUSION: When nodal calcifications and spread
      of nodal masses into the subcutaneous tissue are found in patients with cervical
      lymphadenopathy, the examiner should maintain a high level of clinical suspicion
      for atypical mycobacterial lymphadenitis. Contrary to other causes of cervical
      lymphadenopathy, total surgical excision is the treatment of choice.
      Identification of these patients prior to surgery is therefore of utmost
      importance. Our data suggest that sonography could serve as an easy non-invasive
      method for this purpose.

PMID- 16894509
TI  - Cervical rib--preliminary data on diagnosis by ultrasound.
AB  - AIM: To determine whether ultrasound is useful in detecting cervical rib.
      Ultrasound was used to diagnose cervical rib in five patients with neck pain and
      the findings were compared to those from plain radiography. MATERIALS AND
      METHODS: Ultrasound was used in 34 patients with pain and stiffness in the neck
      region. The area concerned was scanned sonographically in both longitudinal and
      transverse planes. In the sitting position, plain radiographs were obtained after
      ultrasound examination for comparison and verification. The contralateral side of
      the neck was used as control. RESULTS: Sonography revealed abnormalities in five
      patients. Sonography and X-ray confirmed the diagnosis of cervical rib in six
      patients, whereas one patient had a lipoma of the neck. CONCLUSION: Sonography is
      an additional and easily available diagnostic modality for the detection of
      cervical rib in cases of pain and stiffness in the neck region.

PMID- 16894510
TI  - Ultrasound examination shows disturbed proximal gastric function in symptomatic
      gallstone patients with dyspepsia and improvement after cholecystectomy-
      gallstones and gastric emptying.
AB  - AIM: The aim of our study was to examine gastric function, gallbladder emptying,
      and dyspepsia in symptomatic gallbladder stone patients (SGBS) to see if a
      motility disorder, expressed by gastric function and gallbladder emptying, may
      cause dyspepsia in SBGS. MATERIALS AND METHODS: Gastric function and gallbladder
      emptying in 21 SGBS referred for surgical treatment were measured by ultrasound
      after ingestion of 500 ml of a meat soup (bouillon). Dyspeptic symptoms were
      simultaneously recorded on a Visual Analog Scale (VAS). The patients were re
      examined 10 months after cholecystectomy. Hospital staff (n = 14) served as
      control subjects (C). RESULTS: In SGBS, the frontal diameter of the proximal
      stomach was wider than in C at both 10 minutes (55.7 vs. 48.3 mm; p = 0.053) and
      20 minutes (49.3 vs. 39.5 mm; p = 0.002), and the sagittal area of the proximal
      stomach was larger at 10 minutes (25.0 vs. 20.9 cm (2); p = 0.03). The
      postprandial frontal diameter decreased significantly after cholecystectomy
      (immediately after the meal: 51.3 mm; p = 0.03, at 10 minutes: 47.6 mm; p = 0.05,
      and at 20 minutes: 39.1 mm; p = 0.004). Twenty minutes after meal ingestion,
      gallbladder emptying was significantly less in SGBS than in C with a mean (SD)
      emptying of 20 % (17) versus 33 % (18); p < 0.04. In the fasting state, SGBS felt
      more hunger than C (VAS 67 mm vs. 39 mm; p = 0.03). After cholecystectomy, the
      feeling of hunger decreased (VAS 27 mm; p = 0.01). CONCLUSION: SGBS had a wider
      proximal stomach and more hunger in the fasting state than C. After
      cholecystectomy the proximal stomach function and the hunger score improved. Our
      results suggest a physiological link between symptomatic gallstone disease and
      dyspepsia expressed by impaired proximal gastric function.

PMID- 16894511
TI  - Challenges in identifying new antimicrobial agents effective for treating
      infections with Acinetobacter baumannii and Pseudomonas aeruginosa.
AB  - Acinetobacter baumannii and Pseudomonas aeruginosa are gram-negative pathogens
      that target immunocompromised patients. They express a variety of determinants
      that confer resistance to a broad array of antimicrobial agents. Mechanisms of
      resistance include impaired entry through the bacterial outer membrane,
      production of antibiotic-modifying enzymes, active efflux, and target mutations
      that reduce antimicrobial affinity. It has been a challenge to identify new
      agents that have activity against the more resistant variants of these species.
      Doripenem is a carbapenem in phase 3 trials that has excellent activity against
      P. aeruginosa and A. baumannii. However, it lacks activity against strains that
      express resistance to the currently available carbapenems. Tigecycline is a newly
      licensed glycylcycline that lacks activity against P. aeruginosa but has
      encouraging activity against many A. baumannii isolates. Resistance to
      tigecycline can emerge during therapy, however, and is due to expression of
      multidrug efflux pumps.

PMID- 16894512
TI  - Quantitative cultures for diagnosing ventilator-associated pneumonia: a critique.
AB  - The diagnosis of ventilator-associated pneumonia has been clouded by uncertainty,
      because a reference standard has never been established. The use of invasive
      procedures to obtain respiratory tract samples for culture, with quantitation of
      the bacteria isolated, has been the approach most commonly advocated.
      Quantitation of bacteria from lower respiratory tract specimens can be used to
      distinguish colonization from infection. We review the invasive procedures
      (bronchoalveolar lavage, protected specimen brushing, nonbronchoscopic
      bronchoalveolar lavage, and blinded bronchial sampling), the methods of
      quantitation used, the types of catheters used, the sample collection methods,
      and the criteria used as cutoffs for the quantitative cultures. Quantitation of
      lower respiratory tract samples is inherently unstable from a mathematical
      perspective, given the variability in the volume of fluid instilled and
      reaspirated and the magnitude and complexity of the area being sampled. We also
      briefly review the use of quantitation for bacterial infections other than
      pneumonia, including urinary tract infection and catheter-related bacteremia. The
      variability in both the methods and reference criteria in the studies reviewed
      show that the quantitation approach is neither standardized nor evidence based.

PMID- 16894514
TI  - The epidemiological profile of infections with multidrug-resistant Pseudomonas
      aeruginosa and Acinetobacter species.
AB  - Isolates of Pseudomonas aeruginosa or Acinetobacter species that are resistant to
      all, or almost all, commercially available antibiotics are now prevalent
      worldwide. Typically, these strains are recovered from patients in intensive care
      units who have ventilator-associated pneumonia. "Panresistant" strains can be
      defined as strains that are resistant to all beta -lactam and quinolone
      antibiotics recommended as empirical therapy for ventilator-associated pneumonia.
      These strains are well adapted to the hospital environment--molecular
      epidemiological studies have frequently revealed that only 1 or 2 clones caused
      outbreaks in intensive care units. However, panresistant strains may also be
      selected by antibiotic use. Given the lack of antibiotic options to treat
      infection with panresistant strains, enhanced surveillance for these organisms is
      necessary at unit-specific, institutional, and national levels.

PMID- 16894515
TI  - Mechanisms of multidrug resistance in Acinetobacter species and Pseudomonas
      aeruginosa.
AB  - Acinetobacter species and Pseudomonas aeruginosa are noted for their intrinsic
      resistance to antibiotics and for their ability to acquire genes encoding
      resistance determinants. Foremost among the mechanisms of resistance in both of
      these pathogens is the production of beta -lactamases and aminoglycoside
      modifying enzymes. Additionally, diminished expression of outer membrane
      proteins, mutations in topoisomerases, and up-regulation of efflux pumps play an
      important part in antibiotic resistance. Unfortunately, the accumulation of
      multiple mechanisms of resistance leads to the development of multiply resistant
      or even "panresistant" strains.

PMID- 16894517
TI  - Antibiotic regimens and intestinal colonization with antibiotic-resistant gram
      negative bacilli.
AB  - The intestinal tract provides an important reservoir for antibiotic-resistant
      gram-negative bacilli, including Enterobacteriaceae species, Pseudomonas
      aeruginosa, and Acinetobacter baumannii. Selective pressure exerted by
      antibiotics plays a crucial role in the emergence and dissemination of these
      pathogens. Many classes of antibiotics may promote intestinal colonization by
      health care-associated gram-negative bacilli, because the organisms are often
      multidrug resistant. Antibiotics may inhibit colonization by gram-negative
      pathogens that remain susceptible, but the benefits of this effect are often
      limited because of the emergence of resistance. Antibiotic formulary alterations
      and standard infection control measures have been effective in controlling
      outbreaks of colonization and infection with antibiotic-resistant gram-negative
      pathogens. Additional research is needed to clarify the role of strategies such
      as selective decontamination of the digestive tract and decontamination of
      environmental surfaces and of patients' skin and wounds.

PMID- 16894516
TI  - What infection control interventions should be undertaken to control multidrug
      resistant gram-negative bacteria?
AB  - Multidrug-resistant gram-negative bacteria are an emerging problem. The present
      article addresses 2 relevant questions: (1) should active surveillance be
      performed to identify patients colonized with multidrug-resistant gram-negative
      bacteria, and (2) should contact isolation precautions be taken with patients
      colonized or infected with multidrug-resistant gram-negative bacteria? Data and
      variables that are needed to scientifically answer these questions are reviewed,
      as are existing data on Pseudomonas aeruginosa, Enterobacteriaceae (Escherichia
      coli and Klebsiella species in particular), and Acinetobacter baumannii.

PMID- 16894518
TI  - Selective digestive tract decontamination--will it prevent infection with
      multidrug-resistant gram-negative pathogens but still be applicable in
      institutions where methicillin-resistant Staphylococcus aureus and vancomycin
      resistant enterococci are endemic?
AB  - The purposes of selective decontamination of the digestive tract are to treat
      infections that may be incubating at the time a patient is admitted to an
      intensive care unit (ICU), by intravenous administration of antibiotics during
      the first days of a stay in the ICU, and to prevent ICU-acquired infections, by
      topical application of antibiotics in the oropharynx and the gastrointestinal
      tract. Despite multiple trials in which a considerable reduction in the incidence
      of ventilator-associated pneumonia was demonstrated, major objections against the
      routine use of selective decontamination of the digestive tract have included a
      lack of demonstrated reductions in mortality rates and in length of stay (in
      individual trials), a lack of cost-efficacy data, and the threat of selection of
      multidrug-resistant bacteria. Recently, 2 controlled, randomized studies reported
      significant reductions in mortality rates among patients in ICUs who underwent
      selective decontamination of the digestive tract in combination with reduced
      selection of antibiotic-resistant pathogens. However, those studies were
      performed in settings where levels of antibiotic resistance are low, and some
      methodological issues remain unresolved. If these beneficial results are
      confirmed, the question of how to balance these benefits against the expected
      enhanced selection of methicillin-resistant Staphylococcus aureus, vancomycin
      resistant enterococci, and, possibly, multidrug-resistant gram-negative bacteria
      will emerge.

PMID- 16894519
TI  - Use of quantitative cultures and reduced duration of antibiotic regimens for
      patients with ventilator-associated pneumonia to decrease resistance in the
      intensive care unit.
AB  - Ventilator-associated pneumonia is responsible for approximately half of the
      infections acquired in the intensive care unit and represents one of the
      principal reasons for the prescription of antibiotics in this setting. Invasive
      diagnostic methods, including bronchoalveolar lavage and/or protected specimen
      bronchial brushing, could improve the identification of patients with true
      bacterial pneumonia and facilitate decisions of whether to treat. These
      techniques also permit rapid optimization of the choice of antibiotics in
      patients with proven bacterial infection, once the results of respiratory tract
      cultures become available, based on the identity of the specific pathogens and
      their susceptibility to specific antibiotics, to avoid prolonged use of a broader
      spectrum of antibiotic therapy than is justified by the available information.
      Because unnecessary prolongation of antibiotic therapy for patients with true
      bacterial infection may lead to the selection of multidrug-resistant
      microorganisms without improving clinical outcome, efforts to reduce the duration
      of therapy for nosocomial infections are also warranted. An 8-day regimen can
      probably be standard for patients with ventilator-associated pneumonia. Possible
      exceptions to this recommendation include immunosuppressed patients, patients who
      are bacteremic or whose initial antibiotic therapy was not appropriate for the
      causative microorganism(s), and patients whose infection is with very difficult
      to-treat microorganisms and show no improvement in clinical signs of infection.

PMID- 16894520
TI  - Is antibiotic cycling the answer to preventing the emergence of bacterial
      resistance in the intensive care unit?
AB  - Antibiotic resistance has emerged as an important determinant of mortality for
      patients in the intensive care unit (ICU) setting. This is largely due to the
      increasing presence of pathogenic microorganisms with resistance to existing
      antibiotic agents, resulting in the administration of inappropriate treatment.
      Escalating antibiotic resistance has also been associated with greater overall
      health care costs, as a result of prolonged hospitalizations and convalescence
      associated with failure of antibiotic treatment, the need to develop new
      antibiotic agents, and the implementation of broader infection control and public
      health interventions aimed at curbing the spread of antibiotic-resistant
      pathogens. Antibiotic cycling has been advocated as a tool to reduce the
      occurrence of antibiotic resistance, especially in the ICU setting.
      Unfortunately, the cumulative evidence to date suggests that antibiotic cycling
      has limited efficacy for preventing antibiotic resistance. Nevertheless, a
      strategy whereby multiple or all classes of antibiotics are available for use
      (i.e., antibiotic heterogeneity) can be part of a broader effort aimed at
      curtailing antibiotic resistance within ICUs. Such efforts should be routine,
      given the limited availability of new antibiotic drug classes for the foreseeable
      future.

PMID- 16894521
TI  - Parenteral and inhaled colistin for treatment of ventilator-associated pneumonia.
AB  - The spectrum of available therapeutic options has become drastically narrowed in
      recent years, particularly for nosocomial multidrug-resistant gram-negative
      pathogens. This therapeutic void has created a resurgence of interest in
      colistin. In 5 published series since 1999, clinical response rates for pneumonia
      due to Pseudomonas aeruginosa or Acinetobacter baumannii treated with intravenous
      colistin have ranged from 25% to 62%, despite high severity of illness at
      baseline. De novo nephrotoxicity was observed in 8%-36% of patients, despite
      close attention to both appropriate dosing and duration of treatment.
      Neurotoxicity, which was commonly described in the old colistin era, has been
      exceedingly rare in recent experience. Aerosolized therapy as an adjunct to
      systemic treatment appears promising, but the current published data are much too
      limited to allow determination of the incremental benefit of the addition of
      aerosolized treatment to systemic treatment. Colistin is a reasonably safe last
      line therapeutic alternative for pneumonia due to multi- or panresistant P.
      aeruginosa or A. baumannii.

PMID- 16894522
TI  - Novel antibiotic combinations against infections with almost completely resistant
      Pseudomonas aeruginosa and Acinetobacter species.
AB  - For infections with antibiotic-susceptible strains of Pseudomonas aeruginosa,
      most studies have suggested that combination therapy, usually with a beta -lactam
      antibiotic plus an aminoglycoside, is preferable for patients with bacteremia and
      neutropenia. Against infections with Pseudomonas aeruginosa or Acinetobacter
      baumannii isolates that are resistant to all antibiotics except the polymyxins,
      several novel antibiotic combinations demonstrate increased activity in vitro
      compared with that of any single agent. Whether these combinations yield outcomes
      that are improved over those seen with a polymyxin or other agent alone remains
      to be determined. However, against infections with species resistant to all
      antibiotics, including polymyxins, novel combinations are the only remaining
      therapeutic option.

PMID- 16894523
TI  - Excellent survival, cancer type, and Nottingham grade after atypical lobular
      hyperplasia on initial breast biopsy.
AB  - BACKGROUND: Atypical lobular hyperplasia (ALH) is associated with a 10% to 20%
      risk of subsequent invasive carcinoma, primarily in the ipsilateral breast.
      Nottingham grading, special tumor types, and survival after invasive cancer
      diagnosis were analyzed consistently for the first time. METHODS: A longitudinal
      follow-up study of 252 women who underwent 261 benign surgical biopsies between
      1950 and 1985 with a diagnosis of ALH was undertaken. Subsequent invasive breast
      cancers were graded and subtyped based on histologic features and the cohort
      assessed for cancer survival. RESULTS: Forty-eight (19%) women developed invasive
      breast cancer at an average of 15.1 years. Twenty (42%) of the tumors were
      special subtype tumors with good prognosis. By an average of 13 years after
      invasive cancer diagnosis, 2 (10%) of 20 women with special type and variant
      tumors had died of breast cancer, compared with 9 (32%) of 28 women with tumors
      of no special type (24 tumors) or an unknown type (4 tumors). Only 1 patient with
      a tumor of low Nottingham grade died of breast cancer. CONCLUSIONS: ALH is a
      nonobligate cancer precursor associated with a moderate risk of breast cancer and
      predicts that later cancers are associated with overall excellent survival.
      Nearly half of the subsequent cancers show classic or variant patterns of special
      types with a good prognosis and the majority are of low or intermediate combined
      histologic grade. Treatment of women with ALH should be influenced by their
      modest elevation in breast cancer risk and the good prognosis and low mortality
      of many of these cancers.

PMID- 16894524
TI  - Treatment of pregnant breast cancer patients and outcomes of children exposed to
      chemotherapy in utero.
AB  - BACKGROUND: As women in the US delay childbearing, it has been hypothesized that
      the incidence of breast cancer diagnosed during pregnancy will increase. There
      are very little prospective data on the treatment of pregnant women with breast
      cancer with chemotherapy and even less data on the outcomes of their children who
      were exposed to chemotherapy in utero. METHODS: Fifty-seven pregnant breast
      cancer patients were treated on a single-arm, multidisciplinary, institutional
      review board-approved protocol with FAC (5-fluorouracil, doxorubicin,
      cyclophosphamide) in the adjuvant (n = 32) or neoadjuvant (n = 25) setting.
      Parents/guardians were surveyed by mail or telephone regarding outcomes of
      children exposed to chemotherapy in utero. RESULTS: Of the 57 women, 40 are alive
      and disease-free, 3 have recurrent breast cancer, 12 died from breast cancer, 1
      died from other causes, and 1 was lost to follow-up. Of the 25 patients who
      received neoadjuvant FAC, 6 had a pathologic complete response, whereas 4 had no
      tumor response to chemotherapy and eventually died from their disease. All women
      who delivered had live births. One child has Down syndrome and 2 have congenital
      anomalies (club foot; congenital bilateral ureteral reflux). The children are
      healthy and those in school are doing well, although 2 have special educational
      needs. CONCLUSIONS: Breast cancer can be treated with FAC chemotherapy during the
      second and third trimesters without significant short-term complications for the
      majority of children exposed to chemotherapy in utero. Longer follow-up of the
      children is needed to evaluate possible late side effects such as impaired
      cardiac function and fertility.

PMID- 16894525
TI  - Metabolic syndrome and growth hormone deficiency in adult survivors of childhood
      acute lymphoblastic leukemia.
AB  - BACKGROUND: The purpose of the study was to determine the prevalence of metabolic
      syndrome, growth hormone deficiency, and cardiovascular risk factors among adult
      survivors of childhood acute lymphoblastic leukemia (ALL) treated with or without
      cranial irradiation. METHODS: Follow-up was undertaken of 75 randomly selected
      long-term childhood ALL survivors. Testing included fasting insulin, glucose,
      lipids, and growth hormone (GH) releasing hormone plus arginine stimulation test.
      The prevalence of metabolic syndrome was compared with population norms from 1999
      2002 National Health and Nutrition Examination Study (NHANES) data, and
      internally between those with and without past cranial irradiation and those with
      normal (>16.5 microg/L) versus insufficient (9-16.5 microg/L) versus deficient
      (<9 microg/L) peak GH secretion. RESULTS: The mean subject age was 30 years and
      the mean time since ALL diagnosis was 25 years. The prevalence of metabolic
      syndrome did not differ statistically (P = .87) between study subjects (16.6%)
      and same-age, same-sex population norms (17.5%). However, 60% of subjects treated
      with cranial irradiation, compared with 20% of those who were not, had 2 or more
      of the 5 components of metabolic syndrome. Untreated abnormally low GH was
      present in 64% of subjects overall and 85% of those who received past cranial
      irradiation. Cranial irradiation was strongly related to GH deficiency, and in
      turn lower insulin-like growth factor 1 (IGF-1), higher fasting insulin,
      abdominal obesity, and dyslipidemia, particularly in women. CONCLUSIONS:
      Hematologists who treat childhood ALL patients, and particularly those who
      provide primary care to adult survivors, should be aware of the potential for
      long-term GH deficiency and adverse cardiovascular and diabetes risk profiles as
      a consequence of leukemia treatment.

PMID- 16894526
TI  - Linear accelerator radiosurgery for pituitary macroadenomas: a 7-year follow-up
      study.
AB  - BACKGROUND: A prospective study was conducted to assess the efficacy and side
      effects of linear accelerator (LINAC)-based radiosurgery (RS) performed with a
      reduced dose of therapeutic radiation for patients with surgically inaccessible
      pituitary macroadenomas. METHODS: From August 1990 through January 2004, 175
      patients with pituitary macroadenomas were treated with LINAC-RS according to a
      prospective protocol. To minimize the risk for radiation-induced damage of the
      pituitary function, the therapeutic dose to be applied was limited to 20 grays.
      RESULTS: Among 175 patients, 142 patients who had a minimum follow-up of 12
      months (mean +/- standard deviation, 81.9 +/- 37.2 months) were included in the
      current study. The local tumor control rate was 96.5%, and the tumor response
      rate was 32.4%. The mean time (+/- standard deviation) from LINAC-RS to
      normalization of pathologic hormone secretion was 36.2 +/- 24.0 months. The
      probability for normalization was 34.3% at 3 years and 51.1% at 5 years. The
      frequency of endocrine cure (defined as the normalization of hormone secretion
      without specific medication intake) was 35.2% (mean +/- standard deviation time
      to cure, 42.1 +/- 25.0 months). Patients with Cushing disease had a statistically
      significant greater chance of achieving a cure (P = .001). Side effects of LINAC
      RS were deterioration of anterior pituitary function (12.3%), radiation-induced
      tissue damage (2.8%), and radiation-induced neuropathy (1.4%). CONCLUSIONS: LINAC
      RS using a lower therapeutic radiation dose achieved local tumor control and
      normalization or cure of hormone secretion comparable to the results achieved
      with gamma-knife RS. Compared with the latter, the time to normalization or
      endocrine cure was delayed, most probably as a result of dose reduction. However,
      the lower therapeutic radiation dose did not prevent radiation-induced damage of
      pituitary function completely.

PMID- 16894527
TI  - Relevance of extracapsular extension of pelvic lymph node metastasis in patients
      with bladder cancer treated in the contemporary era.
AB  - BACKGROUND: Previous reports have suggested that extracapsular extension (ECE) is
      a prognostic factor in patients with urothelial carcinoma who have positive lymph
      nodes at the time of radical cystectomy. In the current study, the relevance of
      ECE in patients treated in the contemporary era was evaluated. METHODS: A
      database search from 1993 to 2003 revealed 150 patients with pN+M0 disease
      detected after radical cystectomy; of these, 108 patients did not receive
      neoadjuvant chemotherapy and form the basis of the current report. Overall
      survival (OS), disease-specific survival (DSS), and recurrence-free survival
      (RFS) data were analyzed by the Kaplan-Meier method, with log-rank tests used to
      evaluate associations between survival and variables studied. RESULTS: Five-year
      OS, DSS, and RFS rates were 30.9%, 45.5%, and 29.7%, respectively. Adjuvant
      chemotherapy was administered to 70% of patients. On multivariate analysis,
      adjuvant chemotherapy was significantly associated with prolonged OS, DSS, and
      RFS (P </= .01). For patients overall and when stratified by pN status, the
      presence of ECE of lymph node metastasis was not found to be significantly
      associated with OS (P = .52), DSS (P = .43), or RFS (P = .83). CONCLUSIONS.: The
      current study suggests that ECE is not an independent prognostic factor in a
      contemporary series of patients with positive lymph nodes at radical cystectomy.
      This might be reflective of a paradigm shift that encompasses the adoption of
      multimodal therapy.

PMID- 16894528
TI  - Role of spinal MRI in the follow-up of children treated for medulloblastoma.
AB  - BACKGROUND: The purpose of the current study was to describe the usefulness of
      spinal magnetic resonance imaging (MRI) in children with medulloblastoma or
      primitive neuroectodermal tumor (PNET) of the posterior fossa. METHODS: Children
      consecutively diagnosed with medulloblastoma/PNET and followed in the Hospital
      for Sick Children/Toronto were identified. A homogenous cohort of children
      treated with craniospinal irradiation as part of their initial treatment was
      considered. Contrast-enhanced spinal MRIs done concomitantly with cranial MRIs
      (doublets) were reviewed. Recurrence was defined as any new abnormal lesion (in
      the brain or in the spine) in symptomatic or asymptomatic patients. Doublets
      after the first recurrence were excluded in the final analysis. The utility of a
      spinal MRI in the presence of a negative cranial MRI was assessed. RESULTS: In
      all, 73 patients (21 females and 52 males; median age, 6.6 years, median follow
      up time, 4.3 years) had at least 1 evaluable doublet during the follow-up period.
      Since concomitant cranial and spinal MRI was introduced as the standard
      evaluation for medulloblastoma/PNET in 1991, 286 doublets were evaluable.
      Fourteen spinal MRIs and 25 cranial MRIs showed new nodular or leptomeningeal
      lesions. In 2 patients, repeat MRIs ruled out recurrence (false-positive). All
      confirmed spinal recurrences were associated with intracranial recurrence. Of 261
      doublets with negative cranial MRI, no new lesion was identified on spinal MRI.
      CONCLUSIONS: An absence of progression on cranial MRI is highly predictive of
      absence of progression on spinal MRI. There is little evidence that surveillance
      spinal MRI (in children who underwent craniospinal radiation as part of their
      initial treatment) improves the detection of recurrences in children with
      medulloblastoma.

PMID- 16894529
TI  - Increased expression of avian erythroblastosis virus E26 oncogene homolog 1 in
      World Health Organization grade 1 meningiomas is associated with an elevated risk
      of recurrence and is correlated with the expression of its target genes matrix
      metalloproteinase-2 and MMP-9.
AB  - BACKGROUND: The transcription factor avian erythroblastosis virus E26 (V-Ets)
      oncogene homolog 1 (Ets-1) is involved in tumor development and progression
      through the transcriptional regulation of several matrix-degrading enzyme
      systems, including matrix metalloproteinases (MMPs). It has been demonstrated
      that the MMPs are expressed strongly in high-grade meningiomas. To determine the
      biologic significance of Ets-1 in the progression of benign meningiomas, the
      authors investigated the expressions of Ets-1 and its target genes MMP-2 and MMP
      9 in primary and recurrent, Grade 1 meningiomas. METHODS: The expression levels
      of Ets-1, MMP-2, and MMP-9 were examined by immunohistochemistry in 70 Grade 1
      meningiomas, including 36 primary tumors without recurrence after 5 years of
      follow-up and 17 pairs of primary tumors and subsequent recurrences. RESULTS: The
      results demonstrated higher expression of Ets-1, MMP-2, and MMP-9 proteins in
      meningiomas with subsequent recurrences compared with meningiomas from patients
      who had no recurrences (P < .001). In addition, Ets-1 expression was correlated
      with the expression of both MMP-2 and MMP-9. CONCLUSIONS: Ets-1 may be involved
      in meningioma recurrence by up-regulating MMP-2 and MMP-9. Increased expression
      of these genes in World Health Organization grade 1 meningiomas may serve as an
      indicator for a high risk of recurrence.

PMID- 16894530
TI  - Molecular aspects on the interaction of protoberberine, benzophenanthridine, and
      aristolochia group of alkaloids with nucleic acid structures and biological
      perspectives.
AB  - Alkaloids occupy an important position in chemistry and pharmacology. Among the
      various alkaloids, berberine and coralyne of the protoberberine group,
      sanguinarine of the benzophenanthridine group, and aristololactam-beta-d
      glucoside of the aristolochia group have potential to form molecular complexes
      with nucleic acid structures and have attracted recent attention for their
      prospective clinical and pharmacological utility. This review highlights (i) the
      physicochemical properties of these alkaloids under various environmental
      conditions, (ii) the structure and functional aspects of various forms of
      deoxyribonucleic acid (DNA) (B-form, Z-form, H(L)-form, protonated form, and
      triple helical form) and ribonucleic acid (RNA) (A-form, protonated form, and
      triple helical form), and (iii) the interaction of these alkaloids with various
      polymorphic DNA and RNA structures reported by several research groups employing
      various analytical techniques like absorbance, fluorescence, circular dichroism,
      and NMR spectroscopy; electrospray ionization mass spectrometry, thermal melting,
      viscosity, and DNase footprinting as well as molecular modeling and thermodynamic
      studies to provide detailed binding mechanism at the molecular level for
      structure-activity relationship. Nucleic acids binding properties of these
      alkaloids are interpreted in relation to their biological activity.

PMID- 16894531
TI  - Cysteinyl-leukotrienes and their receptors in asthma and other inflammatory
      diseases: critical update and emerging trends.
AB  - Cysteinyl-leukotrienes (cysteinyl-LTs), that is, LTC4, LTD4, and LTE4, trigger
      contractile and inflammatory responses through the specific interaction with G
      protein-coupled receptors (GPCRs) belonging to the purine receptor cluster of the
      rhodopsin family, and identified as CysLT receptors (CysLTRs). Cysteinyl-LTs have
      a clear role in pathophysiological conditions such as asthma and allergic
      rhinitis (AR), and have been implicated in other inflammatory conditions
      including cardiovascular diseases, cancer, atopic dermatitis, and urticaria.
      Molecular cloning of human CysLT1R and CysLT2R subtypes has confirmed most of the
      previous pharmacological characterization and identified distinct expression
      patterns only partially overlapping. Interestingly, recent data provide evidence
      for the immunomodulation of CysLTR expression, the existence of additional
      receptor subtypes, and of an intracellular pool of CysLTRs that may have roles
      different from those of plasma membrane receptors. Furthermore, genetic variants
      have been identified for the CysLTRs that may interact to confer risk for atopy.
      Finally, a crosstalk between the cysteinyl-LT and the purine systems is being
      delineated. This review will summarize and attempt to integrate recent data
      derived from studies on the molecular pharmacology and pharmacogenetics of
      CysLTRs, and will consider the therapeutic opportunities arising from the new
      roles suggested for cysteinyl-LTs and their receptors.

PMID- 16894532
TI  - Developmental expression of pluripotency determining factors in caprine embryos:
      novel pattern of NANOG protein localization in the nucleolus.
AB  - Transcription factors, POU5F1/OCT4 and NANOG, whose expression is restricted to
      the inner cell mass (ICM) in mouse and human blastocysts, are used to
      characterize undifferentiated embryonic stem cells (ESC) in vitro. However,
      POU5F1 may not be a useful marker in domestic animals due to its expression in
      both ICM and trophectoderm (TE), while NANOG mRNA and protein expression have
      only been described fully in mice. In an effort to identify ESC markers for
      domestic animals, expression patterns of NANOG, POU5F1, and the cell surface
      markers (SSEA1, SSEA4, TRA-1-60, TRA-1-81) were examined in preimplantation goat
      embryos, a species that has proven to be a superior choice for the production of
      transgenic proteins in milk (biopharming). Our results indicate that while goat
      embryos express POU5F1, SSEA1, and SSEA4 proteins, their expression is not
      strictly restricted to the ICM. In a unique staining pattern, NANOG protein was
      localized to the nucleoplasm and nucleoli in ICM cells, but was localized
      strictly to nucleoli in TE. This pattern may reflect down-regulation of protein
      by sequestration/degradation utilizing a nucleolar mechanism known to operate in
      stem cells. Furthermore, NANOG mRNA in TE was also significantly down-regulated
      as compared with that in ICM. Taken together, this novel expression pattern of
      NANOG in goat preimplantation embryos suggests that NANOG could serve as marker
      of pluripotency in goats and may be useful in derivation and characterization of
      caprine ESC. This study is the first to characterize both NANOG mRNA and protein
      expression in any species other than the mouse.

PMID- 16894533
TI  - Screening of genetic and expression alterations of SRC1 gene in prostate cancer.
AB  - BACKGROUND: Genetic alterations of the SRC1 gene have not been thoroughly studied
      in prostate cancer. MATERIALS AND METHODS: Five prostate cancer cell lines and 32
      xenografts were screened for mutations and gene copy number alterations.
      Subsequently, frequencies of detected sequence variations were further analyzed
      in 44 clinical prostate cancers, 6 benign prostate hyperplasias, and 48 normal
      controls. Finally, the protein expression of SRC1 in 254 clinical prostate tumors
      was investigated. RESULTS: Three non-recurrent sequence variations, and one
      single nucleotide polymorphism in the coding region of SRC1, as well as one case
      of SRC1 gene amplification were found. The protein expression of SRC1 was higher
      in androgen ablation resistant than untreated prostate carcinomas, but the
      difference was not statistically significant (P = 0.0796). CONCLUSIONS: Genetic
      alterations of SRC1 are rare in prostate cancer. The nuclear protein accumulation
      of SRC1 seems to be mildly increased in androgen ablation resistant prostate
      cancers. .

PMID- 16894534
TI  - Potential biomarker for early risk assessment of prostate cancer.
AB  - BACKGROUND: Catechol estrogen quinones (CEQ) derived from 4-hydroxyestrone (4
      OHE1) and 4-hydroxyestradiol (4-OHE2) react with DNA to form depurinating--N7Gua
      and--N3Ade adducts. This damage leads to mutations that can initiate breast and
      prostate cancer. To determine whether this damage occurs in humans, urine samples
      from men with prostate cancer and benign urological conditions, and healthy
      controls were analyzed. The objective was determining whether any of the cancer
      patients had formed the depurinating 4-OHE1(E2)-1-N3Ade adducts. METHODS: The
      adducts were extracted from samples by using affinity columns equipped with a
      monoclonal antibody developed for detecting 4-OHE1(E2)-1-N3Ade adducts. Eluted
      extracts were separated by capillary electrophoresis with field-amplified sample
      stacking and/or ultraperformance liquid chromatography. Absorption/luminescence
      spectroscopies and mass spectrometry were used to identify the adducts. RESULTS:
      4-OHE1-1-N3Ade was detected at higher levels in samples from subjects with
      prostate cancer (n = 7) and benign urological conditions (n = 4) compared to
      healthy males (n = 5). CONCLUSION: This is the first demonstration that CEQ
      derived DNA adducts are present in urine samples from subjects with prostate
      cancer.

PMID- 16894535
TI  - A new generation of monoclonal and recombinant antibodies against cell-adherent
      prostate specific membrane antigen for diagnostic and therapeutic targeting of
      prostate cancer.
AB  - BACKGROUND: Prostate-specific membrane antigen (PSMA) is an excellent candidate
      for targeting prostate cancer by virtue of its restricted expression on prostatic
      epithelial cells and its upregulation on prostatic carcinoma cells. PSMA is
      expressed on the cell surface displaying a specific three-dimensional structure.
      Therefore, only antibodies with a high cell binding activity will have an
      important impact on antibody-based imaging and therapy. METHODS: Monoclonal
      antibodies (mAbs) and single chain antibody fragments (scFvs) were prepared from
      spleen cells of mice that had been immunized either with purified PSMA or a cell
      lysate of prostate cancer LNCaP cells containing native PSMA. mAbs and scFvs were
      screened for reactivity with purified PSMA and binding to PSMA-expressing LNCaP
      cells. RESULTS: From mice immunized with purified PSMA, we obtained three mAbs
      (K7, K12, D20) and four scFvs (G0, G1, G2, G4), which were highly reactive with
      the isolated antigen, but showed weak or no reaction with viable LNCaP cells.
      From mice immunized with unpurified LNCaP lysate, we obtained three mAbs (3/E7,
      3/F11, 3/A12), and one scFv (A5), which were reactive with purified PSMA, also
      showing a strong and specific binding to viable LNCaP cells and PSMA-transfected
      cells. CONCLUSIONS: Our results suggest that only the mAbs and scFvs, that were
      elicited with unpurified LNCaP lysate and not with purified PSMA will be useful
      agents for diagnostic imaging and therapeutic applications of prostate cancer.

PMID- 16894536
TI  - Hyperactivation is the mode conversion from constant-curvature beating to
      constant-frequency beating under a constant rate of microtubule sliding.
AB  - Flagellar beating of hyperactivated golden hamster spermatozoa was analyzed in
      detail using digital image analysis and was compared to that of nonhyperactivated
      (activated) spermatozoa in order to understand the change in flagellar beating
      during hyperactivation and the active microtubule sliding that brought about the
      change in flagellar beating. Hyperactivated flagellar beating, which was
      characterized by a sharp bend in the proximal midpiece and low beat frequency,
      was able to alter the waveform with little change in beat frequency (constant
      frequency beating), whereas activated flagellar beating, which was characterized
      by a slight bend in the proximal midpiece and high beat frequency, was able to
      alter beat frequency with little change in the waveform (constant-curvature
      beating). These results demonstrate that flagellar beating of hyperactivated and
      activated spermatozoa were essentially different modes and that hyperactivation
      was the mode conversion from constant-curvature beating to constant-frequency
      beating. Detailed analysis of flagellar bends revealed that the increase in
      curvature in the proximal midpiece during hyperactivation was due to the increase
      in total length of microtubule sliding in a nearly straight region between bends,
      while the rate of microtubule sliding remained almost constant.

PMID- 16894537
TI  - Protein gene product 9.5 is a spermatogonia-specific marker in the pig testis:
      application to enrichment and culture of porcine spermatogonia.
AB  - Identification and isolation of spermatogonial stem cells (SSCs) are a
      prerequisite for culture, genetic manipulation, and/or transplantation research.
      In this study, we established that expression of PGP 9.5 is a spermatogonia
      specific marker in porcine testes. The expression pattern of PGP 9.5 in
      spermatogonia was compared to cell type-specific protein (GATA-4 or PLZF)
      expression in seminiferous tubules at different ages, and expression levels of
      PGP 9.5, Vasa, and Oct-4 were compared in different cell fractions. Enrichment of
      spermatogonia from 2-week-old (2wo) and 10-week-old (10wo) boars by adhesion to
      laminin, differential plating, or velocity sedimentation followed by differential
      plating was assessed by identification of spermatogonia using expression of PGP
      9.5 as a marker. Compared to the initial samples, spermatogonia were enriched
      twofold in laminin-selected cells (P < 0.05), and fivefold either in cells
      remaining in suspension (fraction I) or in cells slightly attached to the culture
      dish (fraction II) (P < 0.05) after differential plating. Cells in fraction II
      appeared to be superior for future experiments due to higher viability (>90%)
      than in fraction I ( approximately 50%). Velocity sedimentation plus differential
      plating achieved cell populations containing up to 70% spermatogonia with good
      viability (>80%). Enriched spermatogonia from 2wo and 10wo testes could be
      maintained in a simple culture medium without additional growth factors for at
      least 2 weeks and continued to express PGP 9.5. These data provide the basis for
      future studies aimed at refining conditions of germ cell culture and manipulation
      prior to germ cell transplantation in pigs.

PMID- 16894538
TI  - Bannayan-Riley-Ruvalcaba syndrome with reactive nodular lymphoid hyperplasia and
      autism and a PTEN mutation.

PMID- 16894539
TI  - XX male with sex reversal and a de novo 11;22 translocation.

PMID- 16894540
TI  - Multiple aneuploidy recurrence risk.

PMID- 16894541
TI  - Mutation analysis of the FRAS1 gene demonstrates new mutations in a propositus
      with Fraser syndrome.
AB  - Fraser syndrome (OMIM 219000) is a rare, autosomal recessive condition with
      classical features of cryptophthalmos, syndactyly, ambiguous genitalia,
      laryngeal, and genitourinary malformations, oral clefting and mental retardation.
      Mutations causing loss of function of the FRAS1 gene have been demonstrated in
      five patients with Fraser syndrome. However, no phenotype-genotype correlation
      was established and there was evidence for genetic heterogeneity. Fraser syndrome
      is rare and the FRAS1 gene has 75 exons, complicating mutation screening in
      affected patients. We have screened two patients who fulfilled the diagnostic
      criteria for Fraser syndrome and three patients with related phenotypes (two
      patients with Manitoba oculotrichoanal syndrome and one patient with unilateral
      cryptophthalmos and labial fusion) for mutations in FRAS1 to increase the
      molecular genetic data in patients with Fraser syndrome and related conditions.
      We report two new mutations in a patient with Fraser syndrome, a frameshift
      mutation and a deletion of two amino acids that we consider pathogenic as both
      alter the NG2-like domain of the protein. Although we are still unable to clarify
      a phenotype-genotype relationship in Fraser syndrome, our data add to the list of
      mutations associated with this syndrome.

PMID- 16894543
TI  - Anti-apoptotic effect of insulin-like growth factor (IGF)-I and its receptor in
      porcine preimplantation embryos derived from in vitro fertilization and somatic
      cell nuclear transfer.
AB  - Insulin-like growth factor (IGF)-I is a receptor-mediated autocrine and/or
      paracrine growth and/or survival factor for mammalian embryo development. It is
      known to promote the growth and development of mouse preimplantation embryos. The
      present study was designed to investigate the effects of IGF-I (50 ng/ml), anti
      IGF-I receptor antibody (50 ng/ml) and their combination on porcine
      preimplantation embryo development. Furthermore, the mechanism underlying the
      embryotropic effects of IGF-I was evaluated by monitoring the incidence of
      apoptosis and expression of apoptosis-related genes. In both in vitro fertilized
      (IVF) and somatic cell nuclear transfer (SCNT) embryos, culturing with IGF-I
      increased the rate of blastocyst formation and this embryotrophic effect was
      neutralized by culturing with IGF-I along with anti-IGF-I receptor (IGF-IR)
      antibody. Culturing IVF and SCNT embryos with IGF-I significantly increased the
      number of total cells in blastocysts and decreased the number of apoptotic
      nuclei. These effects of IGF-I were also neutralized by culturing with IGF-I
      along with anti-IGF-IR antibody. Expression of the anti-apoptotic Bcl-2 gene was
      increased, while expression of the pro-apoptotic Bax was decreased in both IVF
      and SCNT embryos cultured with IGF-I. In both IVF and SCNT embryos, anti-IGF-IR
      antibody along with IGF-I neutralized the effect of IGF-I on expression of Bcl-2
      and Bax genes. In conclusion, the present study demonstrated that IGF-I through
      its specific receptors improved the developmental competence of IVF and SCNT
      embryos by decreasing the incidence of apoptosis and regulating apoptosis-related
      genes in porcine preimplantation embryos.

PMID- 16894544
TI  - The histamine H1 receptor activates the nitric oxide pathway at fertilization.
AB  - Sperm fusion with the egg initiates a signaling cascade that releases
      intracellular calcium (Ca(i) (2+)) from the endoplasmic reticulum (ER). In sea
      urchins, Ca(2+) is released as a single, large transient via two distinct
      pathways. The first depends on inositol 1,4,5-triphosphate (IP(3)) production and
      triggers the initial phase of Ca(2+) release, while the second depends on nitric
      oxide (NO) production and is thought to maintain the duration of the Ca(2+) wave.
      We identified a sea urchin homolog of the seven trans-membrane G protein-coupled
      receptor for histamine (suH(1)R) on the egg cell surface that activates NO
      production. Treatment with histamine (HA) causes fluctuations in the resting
      levels of NO in the egg, while antagonists or antibodies of H(1)R inhibit the
      rise of NO normally observed at fertilization. Inhibition of suH(1)R function
      decreases the maintenance, but not the amplitude, of the Ca(2+) transient and
      suggests that it is an integral part of the overall pathway leading to egg
      activation at fertilization in sea urchins.

PMID- 16894546
TI  - Developmental potential of aged oocyte rescued by nuclear transfer following
      parthenogenetic activation and in vitro fertilization.
AB  - Mouse oocyte aged in vitro cannot develop normally following activation. To
      investigate the roles of nucleus or cytoplasm elements in oocyte aged in vitro
      process and their subsequent development capability following activation, we
      reconstructed oocytes with MII chromosome spindle and cytoplasm from aged and
      fresh oocytes by nuclear transfer. The subsequent developmental potential after
      parthenogenetic activation (PA) or in vitro fertilization (IVF) was evaluated.
      After nuclear transfer, more than 75.6% of karyoplast and cytoplast pairs can be
      fused and reconstructed oocytes have a normal haploid karyotype. Following PA,
      aged oocytes cannot develop beyond four-cell stage, reconstructed oocytes from
      fresh nucleus and aged cytoplasm developed to blastocyst with a low percentage
      (9.1%). Instead, blastocyst formation rate of reconstructed oocyte from aged
      nucleus and fresh cytoplasm was higher (60.0%). Following IVF, zygote with
      diploid karyotype can be formed from zona pellucida (ZP)-free oocyte. After
      cultured in vitro, aged oocytes cannot develop beyond two-cell; reconstructed
      oocytes from fresh nucleus and aged cytoplasm developed to blastocyst with low
      percentage (15.0%). However, high blastocyst formation rate (86.2%) can be
      obtained from reconstructed oocytes from aged nucleus and fresh cytoplasm.
      Furthermore, after embryo transfer, three viable pups have been obtained,
      although the efficiency is very low. These observation demonstrated that
      cytoplasm is more crucial than nucleus to aging process. Fresh cytoplasm could
      partly rescue nucleus susceptibility to apoptosis from aging in vitro.

PMID- 16894545
TI  - Stable transmission and transcription of newfoundland ocean pout type III fish
      antifreeze protein (AFP) gene in transgenic mice and hypothermic storage of
      transgenic ovary and testis.
AB  - Here we describe the generation of transgenic mice carrying type III fish
      antifreeze protein (AFP) gene and evaluate whether AFP type III protects
      transgenic mouse ovaries and testes from hypothermic storage. AFPs exist in many
      different organisms. In fish, AFPs protect the host from freezing at temperatures
      below the colligative freezing point by adsorbing to the surface of nucleating
      ice crystals and inhibiting their growth. The transgenic expression of AFP holds
      great promise for conferring freeze-resistant plant and animal species. AFP also
      exhibits a potential for the cryopreservation of tissues and cells. In this
      study, we have generated 42 founder mice harboring the Newfoundland ocean pout
      (OP5A) type III AFP transgene and established one transgenic line (the line #6).
      This study demonstrated that AFP gene construct has been stably transmitted to
      the mouse progeny in the F3 generations in the line #6. Furthermore, the presence
      of AFP transcripts was confirmed by RT-PCR analysis on cDNAs from liver, kidney,
      ovarian, and testis tissues of the mouse from F3 generation in this line. These
      results indicate that ocean pout type III AFP gene could be integrated and
      transmitted to the next generation and stably transcribed in transgenic mice. In
      histological analysis of testis and ovarian tissues of nontransgenic control and
      AFP transgenic mice it has been shown that both tissues of AFP transgenic mice
      were protected from hypothermic storage (+4 degrees C). The AFP III transgenic
      mice obtained for the first time in this study would be useful for investigating
      the biological functions of AFP in mammalian systems and also its potential role
      in cryopreservation.

PMID- 16894548
TI  - Gamete interaction: is it species-specific?
AB  - Reproductive isolation is pivotal to maintain species separation and it can be
      achieved through a plethora of mechanisms. In addition, the development of
      barriers to gamete interaction may drive speciation. Such barriers to
      interspecific gamete interaction can be prezygotic or postzygotic. Considering
      the great diversity in animal species, it is easy to assume that regulation of
      the early steps of fertilization is critical to maintain species identity. One
      prezygotic mechanism that is often mentioned in the literature is that gamete
      interaction is limited to gametes of the same species. But do gametes of all
      animals interact in a species-specific way? Are gamete interactions completely
      species-specific or perhaps just species-restricted? In species in which species
      restrictions have been described, is the interspecies barrier at one major step
      in the fertilization process or is it a combination of partially restricted steps
      that together lead to a block in interspecific fertilization? Are the mechanisms
      used to avoid interspecific crosses different between free-spawning organisms and
      those with internal fertilization? This review will address these questions,
      focusing on prezygotic barriers, and will describe what is known about the
      molecular biology that may account for species-limited gamete recognition and
      fertilization.

PMID- 16894547
TI  - Induction of alpha-caveolin-1 (alphaCAV1) expression in bovine granulosa cells in
      response to an ovulatory dose of human chorionic gonadotropin.
AB  - Caveolins are implicated in endocytosis, cholesterol trafficking and signal
      transduction. A cDNA fragment corresponding to caveolin-1 (CAV1) was identified
      in a mRNA profiling expression study in bovine granulosa cells (GC) following
      human chorionic gonadotropin (hCG)-induced ovulation. Thus, we have characterized
      CAV1 cDNA and studied its spatio-temporal expression pattern in bovine ovarian
      follicles. The full-length bovine alphaCAV1 cDNA was cloned and encodes a
      putative 22 kDa protein. Expression of alphaCAV1 was studied in bovine GC
      obtained from follicles at different developmental stages: small follicles (SF: 2
      4 mm), dominant follicles (DF), ovulatory follicles (OF: 24 hr post-hCG), and
      corpus luteum (CL). Semiquantitative RT-PCR analysis showed a 6.5-fold increase
      in alphaCAV1 mRNA in GC of OF versus DF (P < 0.0001), whereas CAV2 mRNA was
      increased by only twofold (P < 0.0007). Temporal expression of alphaCAV1 mRNA
      from OF recovered at 0, 6, 12, 18, and 24 hr after hCG injection showed an 8.5
      fold increase of alphaCAV1 mRNA after 24 hr compared to 0 hr (P < 0.0018) whereas
      no significant variation was detected for CAV2. Immunoblot demonstrated an
      initial increase in alphaCAV1 protein level 12 hr post-hCG, reaching a maximum at
      24 hr. Immunohistochemical localization of CAV1 was observed in GC of OF isolated
      18 and 24 hr after hCG injection, whereas no signal was detected in GC of DF and
      SF. The induction of alphaCAV1 in GC of OF suggests that alphaCAV1 likely
      contributes to control the increase in membrane signaling that occurs at the time
      of ovulation and luteinization.

PMID- 16894549
TI  - The mammalian acrosome as a secretory lysosome: new and old evidence.
AB  - The morphological and biochemical characteristics of the acrosome depart well
      from any other vesicles in somatic cells, making it one of a kind amongst
      secretory vesicles. The components of the acrosome include a mixture of unique
      enzymes like acrosin and other enzymes that when present in somatic cells are
      commonly found in lysosomes, peroxisomes, and even in the cytoplasm. Several
      observations have pointed out that acrosomal biogenesis has unique features not
      previously described in secretory vesicle biogenesis of somatic cells. In this
      review we discuss the evidence supporting a molecular link between the machinery
      involved in lysosome and acrosome biogenesis, link which may help account for the
      acrosome unique composition.

PMID- 16894550
TI  - Expression of stress inducible protein 1 (Stip1) in the mouse testis.
AB  - Phthalate esters are considered endocrine disruptors that interfere with the
      endocrine balance and development of the mammalian testis. Mono-2-ethylhexyl
      phthalate (MEHP), the active metabolite of the ubiquitously used plasticizer di-2
      ethylhexyl phthalate (DEHP), acts upon Sertoli cells as initial target. By
      subtractive cDNA libraries we identified genes deregulated as response to MEHP in
      primary cultures of mouse Sertoli cells. The expression of mouse stress inducible
      protein 1 (Stip1) was detected as upregulated as a result of MEHP exposure. Stip1
      is a cochaperone protein that is homologous to the human heat shock cognate
      protein 70 (hsc70)/heat shock protein 90 (hsp90)-organizing protein (Hop). To
      assess the presence and localization of Stip1 in mouse testis and its potential
      role in stress defense, we studied the expression pattern of the Stip1 protein by
      immunohistochemistry and of the mRNA by in situ hybridization. Both the protein
      and the mRNA of Stip1 were mainly found in the cytoplasm of all types of
      spermatogonia and spermatocytes up till zygotene, the expression decreased during
      late pachytene and was very weak in diplotene spermatocytes and round spermatids.
      Interestingly, this expression pattern resembled the pattern of stress
      sensitivity of spermatogenic cells in that the most sensitive cell types show the
      weakest expression of Stip1. This suggests an important role for Stip1 in the
      ability of germ cells to survive in stress conditions including high
      temperatures.

PMID- 16894551
TI  - Effect of fertilization antigen (FA-1) DNA vaccine on fertility of female mice.
AB  - Vaccination of female mice with recombinant fertilization antigen (FA-1) causes a
      long-term reversible contraceptive effect. Also, a DNA vaccine based upon a
      dodecamer sequence YLP(12) present in sperm causes a reduction in fertility. In
      the present study, the effects of FA-1 DNA vaccine alone, and FA-1 and YLP(12)
      DNA vaccines together were examined. FA-1 495-bp DNA was cloned into pVAX1 vector
      to prepare the DNA vaccine. Four groups of female mice were immunized
      intradermally by using a gene gun with FA-1 DNA, FA-1 DNA + YLP(12) DNA, FA-1 DNA
      + YLP(12) DNA mixed with exogenous synthetic CpG oliogodeoxynucleotide (ODN), or
      vector DNA alone, respectively. Vaccination with all three formulations caused a
      significant reduction in fertility, with FA-1 DNA + YLP(12) DNA mixed with
      exogenous synthetic CpG ODN showing the highest reduction. Vaccination with all
      three formulations raised antibody response in both the sera as well as locally
      in the vaginal tract, with ODN mixed group demonstrating the highest titers.
      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 vaccine
      formulations followed by the IgA class. In vaginal washing, the highest titers
      were obtained by the IgA class followed by the IgG class. Within the IgG class,
      the titers for the IgG2a subclass were significantly greater than the IgG1
      subclass. The immunocontraceptive effects were long-lasting over 1 year of the
      observation period and increased with time. These novel findings indicate that
      the intradermal immunization with a sperm-specific FA-1 DNA vaccine causes a long
      term circulating and local immune response resulting in immunocontraceptive
      effects in female mice. The anti-fertility effects were enhanced when FA-1 DNA
      vaccine was combined with YLP(12) DNA vaccine and injected with ODN.

PMID- 16894552
TI  - Long-term cryopreserved amniocytes retain proliferative capacity and
      differentiate to ectodermal and mesodermal derivatives in vitro.
AB  - Putative stem cells have recently been isolated from several extra-embryonic
      tissues, including Wharton's Jelly and umbilical cord blood. Relevant studies
      have focused on primary cultures established from freshly isolated tissues. In
      this report, we examine the plasticity of 472 cells, a cryopreserved human
      amniocyte cell line originally isolated in 1974. Under conditions conducive for
      proliferation, the amniocytes displayed fibroblast-like morphologies and
      expressed Oct4 and Rex1, genes associated with pluripotency. Perhaps indicative
      of inherent plasticity, 472 cells simultaneously expressed ectodermal beta-III
      tubulin and mesodermal fibronectin. When cultured under conditions that promote
      neural differentiation, the cells adopted neuronal morphologies and expressed
      neuronal genes, including Gap-43, NF-M, tau, and synaptophysin. Exposure to
      culture conditions that encourage osteogenic differentiation resulted in
      increased expression of alkaline phosphatase (ALP) and the deposition of
      mineralized matrix, established markers of bone cell differentiation. In sum,
      this population of human amniocytes appears to be multipotent, capable of in
      vitro differentiation to ectodermal and mesodermal cell types. Retention of this
      plasticity through decades of cryopreservation suggests that amniocytes might be
      candidates for future cell-based therapies.

PMID- 16894553
TI  - Effects of cryopreservation on the developmental competence, ultrastructure and
      cytoskeletal structure of porcine oocytes.
AB  - The purpose of this study was to determine ultrastructural and cytoskeletal
      changes that result from vitrification of porcine germinal vesicle- (GV-) and
      meiosis II- (MII-) stage oocytes. To investigate the effects of vitrification on
      developmental competence, oocytes were divided into three groups: fresh GV
      oocytes (control), vitrified GV-oocytes, and vitrified MII-oocytes. In both GV-
      and MII-oocytes, vitrification resulted in a high proportion with normal
      morphology (92.4 vs. 94.2%, P > 0.05), while vitrified GV-oocytes yielded a
      higher survival rate than did vitrified MII-oocytes (56.8 vs. 41.9%, P < 0.05).
      In vitrified GV-oocytes, 12 of 154 oocytes underwent cleavage after fertilization
      in vitro, and 6 of these developed to the 8-cell stage, 3 developed to the 16
      cell stage, and 3 developed into morulae. No cleavage was obtained from vitrified
      MII-oocytes. For ultrastructural analysis of oocytes, fresh and vitrified-warmed
      GV- and MII-oocytes were randomly selected for transmission electron microscopy
      (TEM). Results showed that vitrification caused various degrees of cryodamage in
      GV-oocytes. Cumulus cells of some oocytes were separated from the cumulus-oocyte
      complex (COC), and the zona pellucida adjacent to cumulus cells was fractured.
      The gap junctions between cumulus cells were ruptured, and many microvilli were
      disrupted or disappeared. Only homogeneous lipid droplets were observed. After
      vitrification, cortical granules still lined the oolemma of MII-oocytes. Only
      morphologically irregular, nonhomogeneous lipid droplets surrounding large
      vacuoles were found. To examine cytoskeletal structures, fresh and vitrified
      warmed MII-oocytes were analyzed by laser-scanning confocal microscopy (LSCM);
      vitrified-warmed GV-oocytes were cultured for 42-44 hr before LSCM. Of 58 control
      oocytes, 79.5% displayed normal spindles with chromosomes aligned along the
      equatorial plate. In vitrified oocytes the percentage with normal spindle
      organization was decreased significantly in both vitrified GV-oocytes and MII
      oocytes (10.1 and 12.9%, respectively, P < 0.05). The proportion of oocytes with
      normal distribution of F-actin was lower for vitrified GV- and MII-oocytes than
      for controls (16.9 and 37.2% vs. 72.3%). Results of this experiment suggest that
      irreversible damage to the cytoskeleton of porcine GV- and MII-oocytes after
      vitrification could be an important factor affecting developmental competence.

PMID- 16894554
TI  - The influence of follicle size, FSH-enriched maturation medium, and early
      cleavage on bovine oocyte maternal mRNA levels.
AB  - Transcription is arrested in the bovine oocyte within the first few hours of in
      vitro maturation, thus the stored maternal mRNAs accumulated in the oocyte are
      essential to sustain development until the Maternal-Zygotic Transition. In vivo
      matured oocytes have superior blastocyst formation rates than in vitro matured
      oocytes, suggesting that the mRNA content of these oocytes is of higher quality.
      To determine which transcripts may be associated with developmental competence, a
      Suppressive Subtractive Hybridization was performed between oocytes collected by
      ovariectomy at 6 hr post-LH surge and oocytes from slaughterhouse collected after
      6 hr of maturation, resulting in a library enriched in these functionally
      important mRNAs. The clones were spotted onto a cDNA microarray and transcripts
      potentially associated with developmental competence were hybridized onto these
      slides. Hybridizations were performed with transcripts up-regulated in oocytes
      cultured for 6 hr in the presence or absence of rFSH in vitro, and secondly with
      transcripts up regulated in early-cleaving embryos versus those at the one-cell
      stage at 36 hr postfertilization. From these hybridizations, 13 candidates were
      selected. Their functional association with embryonic competence was validated by
      measuring their relative transcript levels by quantitative real-time PCR in eight
      different conditions: oocytes cultured with or without rFSH, early--versus late
      cleaving embryos, and oocytes from different follicle sizes (1-3, 3-5, 5-8, and
      >8 mm of diameter). The gene candidates CCNB2, PTTG1, H2A, CKS1, PSMB2, SKIIP,
      CDC5L, RGS16, and PRDX1 showed a significant quantitative association with
      competence compared to BMP15, GDF9, CCNB1, and STK6.

PMID- 16894555
TI  - The transcription factor CREMtau and cAMP regulate promoter activity of the Na,K
      ATPase alpha4 isoform.
AB  - The Na,K-ATPase is an essential enzyme of the plasma membrane that plays a key
      role in numerous cell processes that depend on the transcellular gradients of
      Na(+) and K(+). Among the various isoforms of the catalytic subunit of the Na,K
      ATPase, alpha4 exhibits the most limited pattern of expression, being restricted
      to male germ cells. Activity of alpha4 is essential for sperm function, and
      alpha4 is upregulated during spermatogenesis. The present study addressed the
      transcriptional control of the human Na,K-ATPase alpha4 gene, ATP1A4. We describe
      that a 5' untranslated region of the ATP1A4 gene (designated -339/+480 based on
      the ATP1A4 transcription initiation site) has promoter activity in luciferase
      reporter assays. Computer analysis of this promoter region revealed consensus
      sites (CRE) for the cyclic AMP (cAMP) response element modulator (CREM).
      Accordingly, dibutyryl cAMP (db-cAMP) and ectopic expression of CREMtau, a testis
      specific splice variant of CREM were able to activate the ATP1A4 promoter driven
      expression of luciferase in HEK 293 T, JEG-3 and GC-1 cells. Further
      characterization of the effect of db-cAMP and CREMtau on deleted constructs of
      the ATP1A4 promoter (-339/+80, and +25/+480), and on the -339/+480 region
      carrying mutations in the CRE sites showed that db-cAMP and CREMtau effect
      required the CRE motif located 263 bp upstream the transcription initiation site.
      EMSA experiments confirmed the CRE sequence as a bonafide CREMtau binding site.
      These results constitute the first demonstration of the transcriptional control
      of ATP1A4 gene expression by cAMP and by CREMtau, a transcription factor
      essential for male germ cell gene expression.

PMID- 16894556
TI  - Cellular telephones and non-Hodgkin lymphoma.
AB  - Dramatic increase in hand-held cellular telephone use since the 1980s and excess
      risk of lymphoproliferative malignancies associated with radio-frequency
      radiation (RFR) exposures in epidemiological and experimental studies motivated
      assessment of cellular telephones within a comprehensive US case-control
      investigation of non-Hodgkin lymphoma (NHL). A questionnaire ascertained cellular
      telephone use in 551 NHL cases and 462 frequency-matched population controls.
      Compared to persons who had never used cellular telephones, risks were not
      increased among individuals whose lifetime use was fewer than 10 (odds ratio (OR)
      = 0.9, 95% confidence intervals (CI): 0.6, 1.3), 10-100 (OR = 1.0, 95 % CI: 0.7,
      1.5) or more than 100 times (e.g., regular users, OR = 0.9, 95% CI: 0.6, 1.4).
      Among regular users compared to those who had never used hand-held cellular
      telephones, risks of NHL were not significantly associated with minutes per week,
      duration, cumulative lifetime or year of first use, although NHL was non
      significantly higher in men who used cellular telephones for more than 8 years.
      Little evidence linked use of cellular telephones with total, diffuse large B
      cell lymphoma or follicular NHL. These findings must be interpreted in the
      context of less than 5% of the population reporting duration of use of 6 or more
      years or lifetime cumulative use of 200 or more hours.

PMID- 16894557
TI  - Tobacco smoke and bladder cancer--in the European Prospective Investigation into
      Cancer and Nutrition.
AB  - The purpose of the present study was to investigate the association between
      smoking and the development of bladder cancer. The study population consisted of
      429,906 persons participating in the European Prospective Investigation into
      Cancer and Nutrition (EPIC), 633 of whom developed bladder cancer during the
      follow-up period. An increased risk of bladder cancer was found for both current-
      (incidence rate ratio 3.96, 95% confidence interval: 3.07-5.09) and ex- (2.25,
      1.74-2.91) smokers, compared to never-smokers. A positive association with
      intensity (per 5 cigarettes) was found among current-smokers (1.18, 1.09-1.28).
      Associations (per 5 years) were observed for duration (1.14, 1.08-1.21), later
      age at start (0.75, 0.66-0.85) and longer time since quitting (0.92, 0.86-0.98).
      Exposure to environmental tobacco smoke (ETS) during childhood increased the risk
      of bladder cancer (1.38, 1.00-1.90), whereas for ETS exposure as adult no effect
      was detected. The present study confirms the strong association between smoking
      and bladder cancer. The indication of a higher risk of bladder cancer for those
      who start smoking at a young age and for those exposed to ETS during childhood
      adds to the body of evidence suggesting that children are more sensitive to
      carcinogens than adults.

PMID- 16894561
TI  - Prospective study of vegetable consumption and liver cancer in Japan.
AB  - We examined the relationship between vegetable consumption and the risk of death
      from liver cancer in a cohort study in Japan. This analysis is based on data from
      6,049 subjects aged 40 to 79 years enrolled in a cohort study conducted in
      Fukuoka Prefecture, Japan. The follow-up period was from 1986 to 1999. All liver
      cancer deaths were recorded. The vegetable consumption was classified into 3
      groups: "once per week or less," "2-4 times per week" and "daily intake." The Cox
      proportional hazards models were used to estimate hazard ratios (HRs) and 95%
      confidence interval (95% CI). A total of 51 male and 22 female liver cancer
      deaths were recorded during 62,343 person-years of follow-up. The "once per week
      or less" group was considered the referent group. In males, the multivariate HRs
      of liver cancer deaths were 0.61 (95% CI: 0.33-1.14) and 0.25 (95% CI: 0.11-0.59)
      in the "2-4 times per week" and "daily intake" groups, respectively. In females,
      the multivariate HRs were 0.44 (95% CI: 0.13-1.51) and 0.51 (95% CI: 0.16-1.69),
      respectively. The multivariate HRs were also reported by history of hepatitis and
      cirrhosis. In those without a history of these conditions, the multivariate HRs
      were 0.54 (95% CI: 0.27-1.09) and 0.36 (95% CI: 0.16-0.83). In those with a
      history of these conditions, the multivariate HRs were 0.58 (95% CI: 0.22-1.56)
      and 0.37 (95% CI: 0.13-1.06), respectively. Our study reveals an inverse
      association between vegetable consumption and the risk of death from liver
      cancer. These results provide further evidence of the protective effect of
      vegetables against liver cancer.

PMID- 16894558
TI  - Physical activity and lung cancer risk in the European Prospective Investigation
      into Cancer and Nutrition Cohort.
AB  - Research conducted predominantly in male populations on physical activity and
      lung cancer has yielded inconsistent results. We examined this relationship among
      416,277 men and women from the European Prospective Investigation into Cancer and
      Nutrition (EPIC). Detailed information on recent recreational, household and
      occupational physical activity, smoking habits and diet was assessed at baseline
      between 1992 and 2000. Relative risks (RR) were estimated using Cox regression.
      During 6.3 years of follow-up we identified 607 men and 476 women with incident
      lung cancer. We did not observe an inverse association between recent
      occupational, recreational or household physical activity and lung cancer risk in
      either males or females. However, we found some reduction in lung cancer risk
      associated with sports in males (adjusted RR = 0.71; 95% confidence interval 0.50
      0.98; highest tertile vs. inactive group), cycling (RR = 0.73; 0.54-0.99) in
      females and non-occupational vigorous physical activity. For occupational
      physical activity, lung cancer risk was increased for unemployed men (adjusted RR
      = 1.57; 1.20-2.05) and men with standing occupations (RR = 1.35; 1.02-1.79)
      compared with sitting professions. There was no evidence of heterogeneity of
      physical activity associations across countries, or across any of the considered
      cofactors. For some histologic subtypes suggestive sex-specific reductions,
      limited by subgroup sizes, were observed, especially with vigorous physical
      activity. In total, our study shows no consistent protective associations of
      physical activity with lung cancer risk. It can be assumed that the elevated
      risks found for occupational physical activity are not produced mechanistically
      by physical activity itself but rather reflect exposure to occupation-related
      lung cancer risk factors.

PMID- 16894563
TI  - Use of tight belts and risk of esophageal adenocarcinoma.
AB  - It has recently been hypothesized that the general shift in use from suspenders
      to belts among men might be a factor that could promote reflux, particularly
      among overweight men, and thereby contribute to the alarmingly increasing
      incidence of esophageal and cardia adenocarcinoma. We addressed this hypothesis
      in a nationwide Swedish population-based case-control study, conducted in 1995
      1997. Included were 189 patients with esophageal adenocarcinoma and 262 patients
      with cardia adenocarcinoma, who were compared with 167 patients with esophageal
      squamous cell carcinoma and 820 population-based control participants. Data were
      collected at structured face-to-face interviews with all study participants.
      Tumor classification was uniform and thorough. Odds ratios (OR) with 95%
      confidence intervals (CI), adjusted for potential confounders, were estimated in
      multivariable logistic regression models. Daily use of tight belts 20 years
      earlier did not entail an increased risk of adenocarcinoma of the esophagus (OR
      1.1, 95% CI 0.7-1.8) or cardia (OR 0.8, 95% CI 0.5-1.3) compared to never use.
      Adjustment for reflux symptoms, body mass and other potentially relevant
      covariates did not influence the results. Similarly, in analyses restricted to
      overweight men, no associations were identified. No association with esophageal
      squamous cell carcinoma was found. In conclusion, this study provided no support
      for the hypothesis that use of tight belts is associated with an increased risk
      of developing esophageal or cardia adenocarcinoma.

PMID- 16894562
TI  - Raf kinases: oncogenesis and drug discovery.
AB  - Raf kinase signaling has been thoroughly investigated over the last 20 years. A
      Raf, B-Raf and C-Raf, the 3 mammalian members of the Raf family, are involved in
      a variety of cellular processes such as growth, proliferation, survival,
      differentiation and transformation. The detection of B-RAF mutations in a wide
      variety of human cancers, the description of wildtype and mutant B-RAF as tumor
      antigens in melanoma and the promising outcome of clinical trials evaluating the
      Raf inhibitor Nexavar (Sorafenib, BAY 43-9006) have sparked a broad interest in
      the scientific community. After a short historical detour and an introduction
      into Raf kinase signaling, we are going to discuss here recent outcomes of Raf
      kinase research with respect to tumor formation and give an overview on current
      efforts to develop anticancer therapies interfering with aberrant Raf kinase
      signaling.

PMID- 16894564
TI  - Serum concentrations of estrogens, sex hormone-binding globulin, and androgens
      and risk of breast cancer in postmenopausal women.
AB  - We assessed the relationship between serum concentrations of estrogens,
      androgens, and sex hormone-binding globulin and risk of breast cancer among
      postmenopausal women. Study participants provided serum prior to breast biopsy or
      mastectomy in 3 hospitals in Grand Rapids, Michigan between 1977 and 1987. A
      total of 179 subjects with localized breast cancer were compared to 152 subjects
      with nonproliferative breast changes that have not been associated with elevated
      breast cancer risk. Increasing serum concentrations of estrone and estrone
      sulfate were associated with increases in breast cancer risk; the odds ratios
      (ORs) in the fourth quartiles compared to the first were 2.3 (95% confidence
      interval (CI) 1.1-4.6) for both (p-trend = 0.02 and 0.03, respectively).
      Estradiol and bioavailable estradiol concentrations were associated with
      nonstatistically significant increases in risk. Androstenediol levels were
      associated with risk (p-trend = 0.01); the OR in the fourth compared to the first
      quartile was 2.2 (95% CI 1.0-4.6). Testosterone, dehydroepiandrosterone and
      androstenedione levels were not associated with increased risk. Sex hormone
      binding globulin was associated with a nonsignificant decrease in risk.
      Associations with estrone and estrone sulfate persisted after adjustment for
      androstenediol (ORs for fourth compared to first quartiles were 2.0 (95% CI 0.9
      4.5) and 2.2 (95% CI 1.0-4.6), respectively (p-trend = 0.16 for both). The
      association with androstenediol was attenuated after adjustment for estrone (OR
      for fourth compared to first quartile was 1.6 (95% CI 0.7-3.6); p-trend = 0.13).
      Higher serum concentrations of estrogens were associated with increased breast
      cancer risk in postmenopausal women. Androgen levels were not independently
      associated with substantially increased risk.

PMID- 16894565
TI  - Molecular determinants of irinotecan efficacy.
AB  - Molecular markers predicting the efficacy of CPT-11 based chemotherapies in
      patients with colorectal cancer (CRC) are unknown. Therefore, we investigated
      whether mRNA levels of drug targets (Topoisomerase I, TS), enzymes involved in 5
      FU metabolism (DPD), in angiogenesis (EGFR, IL-8, VEGF) and in DNA-repair/drug
      detoxification (ERCC1, GST-P1) are associated with the clinical outcome of
      patients with CRC treated with first-line CPT-11 based chemotherapy. Thirty three
      patients with metastatic CRC were included in the study. Intratumoral gene
      expression levels were assessed from paraffin-embedded tissue samples, using
      laser capture microdissection and quantitative Real-Time PCR. Complete response
      was observed in 1 patient, partial response in 12 patients, stable disease in 13
      patients and progressive disease in 6 patients. Response was inevaluable for 1
      patient. Patients with complete response or partial response were classified as
      responders, while patients with stable disease or progressive disease were
      classified as nonresponders. High intratumoral mRNA levels of EGFR, ERCC1 and
      GSPT-P1 were each significantly associated with response to CPT-11 based
      chemotherapy. Recursive partitioning analysis showed that mRNA levels of EGFR and
      ERCC1 are primarily responsible for delineating responders from nonresponders.
      Also, the combination of high intratumoral gene expression levels of both EGFR
      and ERCC1 was significantly associated with progression-free survival. The mRNA
      levels of EGFR had a significant correlation with expression levels of ERCC1, GST
      P1 and VEGF. This small retrospective study suggests that gene expression levels
      of EGFR, ERCC1 and GST-P1 may be useful in predicting the clinical outcome of
      patients with metastatic CRC treated with first-line CPT-11 based chemotherapy.

PMID- 16894566
TI  - Aurora-A induces cell survival and chemoresistance by activation of Akt through a
      p53-dependent manner in ovarian cancer cells.
AB  - Aurora-A is frequently altered in epithelial malignancies. Overexpressing Aurora
      A induces centrosome amplification and G2/M cell cycle progression. We have
      previously shown elevated level of Aurora-A in ovarian cancer and activation of
      telomerase by Aurora-A in human mammary and ovarian epithelia. Here we report
      that Aurora-A protects ovarian cancer cells from apoptosis induced by
      chemotherapeutic agent and activates Akt pathway in a p53-dependent manner.
      Ectopic expression of Aurora-A renders cells resistant to cisplatin (CDDP),
      etoposide and paclitaxel-induced apoptosis and stimulates Akt1 and Akt2 activity
      in wild-type p53 but not p53-null ovarian cancer cells. Aurora-A inhibits
      cytochrome C release and Bax conformational change induced by CDDP. Knockdown of
      Aurora-A by RNAi sensitizes cells to CDDP-induced apoptosis and decreases phospho
      Akt level in wild-type p53 cells. Reintroduction of p53 decreases Akt1 and Akt2
      activation and restores CDDP sensitivity in p53-null but not p53-null-Aurora-A
      cells. Inhibition of Akt by small molecule inhibitor, API-2, overcomes the
      effects of Aurora-A-on cell survival and Bax mitochondrial translocation. Taken
      collectively, these data indicate that Aurora-A activates Akt and induces
      chemoresistance in a p53-dependent manner and that inhibition of Akt may be an
      effective means of overcoming Aurora-A-associated chemoresistance in ovarian
      cancer cells expressing wild-type p53.

PMID- 16894568
TI  - Reproductive factors, exogenous hormone use and bladder cancer risk in a
      prospective study.
AB  - Sex is a consistent predictor of bladder cancer: men experience 2-4-fold higher
      age-adjusted rates than women in the U.S. and Europe. The objective of this study
      was to examine whether hormone-related factors are associated with bladder cancer
      in women. We examined parity, age at menarche, age at first birth, age at
      menopause, oral contraceptive use and menopausal hormone therapy (HT) use and
      bladder cancer risk in the Breast Cancer Detection Demonstration Project Follow
      Up Study. Endpoint and exposure information was collected on 54,308 women, using
      annual telephone interviews (1980-86) and 3 mailed, self-administered
      questionnaires (1987-98). During an average follow-up time of 15.3 years, 167
      cases of bladder cancer were identified. Univariate and adjusted rate ratios
      (RRs) were estimated using Poisson regression. Parity, age at menarche, age at
      first birth, age at menopause, and oral contraceptive use were not associated
      with bladder cancer risk. The majority of menopausal women who took HT used
      estrogen therapy (ET). Postmenopausal women with less than 4 years, 4-9 years, 10
      19 years and 20 or more years of ET use had RRs of 1.55 (95% CI = 0.96-2.51),
      1.00 (95% CI = 0.49-2.04), 1.23 (95% CI = 0.62-2.43) and 0.57 (95% CI = 0.14
      2.34), respectively, compared with nonusers (p = 0.50). Findings from this study
      are not consistent with the hypothesis that hormone-related factors in women are
      associated with bladder cancer.

PMID- 16894569
TI  - Anticancer effects of amooranin in human colon carcinoma cell line in vitro and
      in nude mice xenografts.
AB  - Amooranin (AMR), a natural triterpenoid drug isolated and characterized from
      Amoora rohituka stem bark, is cytotoxic to SW620 human colon carcinoma cell line
      with an IC(50) value of 2.9 microg/ml. This novel compound caused depolarization
      of mitochondrial membrane and decrease of membrane potential, indicating initial
      signal of apoptosis induction. The percentage of cells with decreased
      mitochondrial potential ranged from 7.4% at 1 microg/ml to 60.5% at 100 microg/ml
      AMR. Flow cytometric analysis of apoptosis using Annexin-V-FITC staining showed
      that the percentage of apoptotic cells ranged from 7.5% at 1 microg/ml to 59.2%
      at 100 microg/ml AMR. AMR-induced apoptosis was accompanied by redistribution of
      cytochrome c from mitochondria to cytosol as well as down regulation of Bcl-2 and
      Bcl-X(L) proteins in a dose-dependent manner. SW620 human colon carcinoma
      xenograft mice treated with AMR showed significant reduction in tumor growth
      rates compared to saline- and doxorubicin-treated groups. The reduction in tumor
      growth rate was better in xenografts treated with 2 mg/kg AMR than 5 and 10 mg/kg
      treated mice. The analysis of global gene expression changes induced by AMR in
      xenograft tumors by microarray hybridization revealed that several genes involved
      in energy pathways, transport, apoptosis, immune response, nucleic acid
      metabolism, protein metabolism, cell growth and/or maintenance, signal
      transduction and cell communication, were affected by this natural cancer drug.
      These results suggest that the anticancer properties of AMR in SW620 human colon
      carcinoma cell line are mediated through its effects on functional genomics,
      targeting the apoptotic process.

PMID- 16894570
TI  - Automated method to measure trabecular thickness from microcomputed tomographic
      scans and its application.
AB  - Trabeculae form the internal bony mesh work and provide strength to the bone;
      interconnectivity, overall density, and trabecular thickness are important
      measures of the integrity of the internal architecture. Such strength is achieved
      only gradually during ontogeny, whereby an increase in trabecular thickness
      precedes an increase in mineralization. Loss of bone mass later in life may be
      compensated for by thickening of the remaining trabeculae. These facts, and the
      role of trabeculae in mineral homeostasis, highlight the importance of
      investigating trabecular thickness within and between species. While
      nondestructive imaging techniques (i.e., muCT and MRI) are becoming increasingly
      popular, quantification of trabecular thickness using nondestructive techniques
      has proved difficult owing to limitations imposed by scanning parameters, uniform
      thresholding, and partial volume averaging. Here we present a computer
      application, which aims to overcome these problems. Validation is carried out
      against a phantom and against trabecular thickness measured in corresponding
      histological sections. Good agreement was found between these measurements.
      Furthermore, when trabecular thickness is recorded for modern human fetal ilia, a
      trend toward trabecular thickness increase is found and is in line with reports
      of ontogenetic morphometric changes using histological sections. However, there
      are discrepancies. These may in part be due to partial volume effects of
      obliquely oriented structures. More crucial, however, are problems inherent in
      histological sections, e.g., shrinkage and distortion, especially where
      differences in mineralization are concerned; this may affect biological
      interpretations.

PMID- 16894571
TI  - Material properties of the dentate maxilla.
AB  - The aim of this study was to determine regional variability of material
      properties in the dentate maxilla. Cortical samples were removed from 15 sites of
      15 adult dentate fresh-frozen maxillas. Cortical thickness, density, elastic
      properties, and the direction of greatest stiffness were obtained. Results showed
      that cortical bone in the alveolar region tended to be thicker, less dense, and
      less stiff. Cortical bone from the body of the maxilla was thinner, denser, and
      stiffer. Palatal cortical bone was intermediate in some features but overall was
      more similar to cortical bone from the alveolar region. The principal axes of
      stiffness varied regionally. The regions with the greatest consistency were the
      alveolar area and the frontomaxillary pillar, where the grain of the cortical
      bone was aligned vertically from the incisors to the medial external aspect of
      the orbit. Elastic properties in the human maxilla, especially the orientation of
      the principal axes of stiffness, were more variable than in the mandible.
      Incorporation of these properties into finite-element models should improve their
      accuracy and reliability.

PMID- 16894572
TI  - Clavicle, a neglected bone: morphology and relation to arm movements and shoulder
      architecture in primates.
AB  - In spite of its importance for movements of the upper limbs, the clavicle is an
      infrequently studied shoulder bone. The present study compares clavicular
      morphology among different extant primates. Methods have included the assessment
      of clavicular curvatures projected on two perpendicular planes that can be
      assessed overall as cranial and dorsal primary curvatures. Results showed that in
      cranial view, three morphologies can be defined. One group exhibited an external
      curvature considerably more pronounced than the internal one (Gorilla, Papio); a
      second group was characterized by an internal curvature much more pronounced than
      the external one (Hylobates, Ateles); and a third group contained those with the
      two curvatures equally pronounced (Pan, Homo, Pongo, Procolobus, Colobus).
      Clavicle curvatures projected on the dorsal plane could be placed into four
      groups. The first group is characterized by two curvatures, an inferior and a
      superior (Apes, Spider monkeys). The second included monkeys, whose clavicles
      have an inferior curvature much more pronounced than the superior one. The third
      group includes only Hylobates, whose clavicles possess only the superior
      curvature. The last group includes only modern humans, whose clavicles show only
      the inferior curvature, which is less pronounced than that which exists in
      monkeys. Curvatures in cranial view relate information regarding the parameters
      of arm elevation while those in dorsal view offer insights into the position of
      the scapula related to the thorax. The use of clavicular curvature analysis
      offers a new dimension in assessment of the functional morphology of the clavicle
      and its relationship to the shoulder complex.

PMID- 16894573
TI  - Preparation of enzymatically active human Myc-tagged-NCre recombinase exhibiting
      immunoreactivity with anti-Myc antibody.
AB  - The Cre-loxP system has been recognized as a tool for conditional gene targeting
      in mice. However, most anti-Cre antibodies fail to react with Cre expressed in
      vivo. In an attempt to directly detect Cre by antibodies in vivo, we constructed
      the tagged-NCre (NCreMH) gene by connecting the human Myc and His tag sequences
      to the 3' end of the NCre gene carrying a nuclear localizing signal (NLS)
      sequence. The production of NCre protein and the recombinase activity were
      detected after co-transfection with pCMV-NCreMH and pCETZ-17 carrying the loxP
      flanked lacZ gene into NIH3T3 cells. This activity was also confirmed in vivo
      after gene transfer of pCMV-NCreMH and pCRTEIL-6 carrying loxP-flanked HcRed1 and
      EGFP cDNAs, into oviductal epithelium by electroporation. Immunohistochemical
      staining using anti-Myc antibody demonstrated that the area positive for enhanced
      green fluorescent protein (EGFP) fluorescence was immunostained with the
      antibody. These findings indicate that NCreMH is useful as an alternative to NCre
      for gene targeting.

PMID- 16894574
TI  - Lipopolysaccharide accelerates caspase-independent but cathepsin B-dependent
      death of human lung epithelial cells.
AB  - Caspase-independent cell death has drawn increasing attention. In the present
      study, we found that lipopolysaccharide (LPS) accelerated spontaneous death of
      human lung epithelial A549 cells in a serum- and cell density-dependent manner:
      while serum starvation has been demonstrated to induce apoptosis in the same cell
      line, LPS-induced cell death was only observed in the presence of serum; in
      addition, the cell death was not observed when the cells were seeded at 10- or
      100-fold lower density. The apoptotic features were demonstrated by TUNEL assay,
      DNA laddering and Annexin V staining. However, treatment of cells with two
      commonly used pan-caspase inhibitors, zVAD.fmk or BOC-D.fmk, failed to block cell
      death. In contrast, two cathepsin B inhibitors, Ca074-Me or N-1845, reduced cell
      death significantly. A time-dependent activation of cathepsin B, but not caspase
      3, was observed in both control and LPS-treated cells. Although LPS did not
      further activate cathepsin B or its release, it increased expression and
      translocation of apoptosis inducing factor from mitochondria to the nucleus, and
      increased release of cytochrome c from mitochondria. LPS-induced cell death was
      significantly attenuated by either N-acetyl-L-cysteine or pyrrolidine
      dithiocarbamate, both free radical scavengers. Disruption of lipid raft formation
      with filipin or methyl-beta-cyclodextrin also reduced apoptosis significantly,
      suggesting that lipid raft-dependent signaling is essential. These data imply
      that confluent cells undergo spontaneous cell death mediated by cathepsin B; LPS
      may accelerate this caspase-independent cell death through release of
      mitochondrial contents and reactive oxygen species.

PMID- 16894575
TI  - Excitation UNFOLD (XUNFOLD) to improve the temporal resolution of multishot
      tailored RF pulses.
AB  - An extension of the "UNaliasing by Fourier encoding the Overlaps using the
      temporaL Dimension" (UNFOLD) method to the excitation domain (XUNFOLD) is
      presented to improve the temporal resolution of multishot tailored RF (TRF)
      pulses. Multishot three-dimensional TRF pulses were designed to produce a time
      series of images with periodically aliased excitation profiles. The XUNFOLD
      method is shown to remove the excitation profile aliasing from the dynamic
      imaging data by filtering in the temporal frequency dimension. The technique is
      demonstrated to improve the temporal resolution of simulated functional MRI
      (fMRI) activation in a time series of brain images.

PMID- 16894577
TI  - PCI for LMCA stenosis--is it time to ride the rank bull?

PMID- 16894576
TI  - Imminent extinction of brachy(saurus)therapy for the treatment of in-stent
      restenosis.

PMID- 16894578
TI  - Two-point water-fat imaging with partially-opposed-phase (POP) acquisition: an
      asymmetric Dixon method.
AB  - A novel two-point water-fat imaging method is introduced. In addition to the in
      phase acquisition, water and fat magnetization vectors are sampled at partially
      opposed-phase (POP) rather than exactly antiparallel as in the original Dixon
      method. This asymmetric sampling encodes more valuable phase information for
      identifying water and fat. From the magnitudes of the two complex images, a big
      and a small chemical component are first robustly obtained pixel by pixel and
      then used to form two possible error phasor candidates. The true error phasor is
      extracted from the two error phasor candidates through a simple procedure of
      regional iterative phasor extraction (RIPE). Finally, least-squares solutions of
      water and fat are obtained after the extracted error phasor is smoothed and
      removed from the complex images. For noise behavior, the effective number of
      signal averages NSA* is typically in the range of 1.87-1.96, very close to the
      maximum possible value of 2. Compared to earlier approaches, the proposed method
      is more efficient in data acquisition and straightforward in processing, and the
      final results are more robust. At both 1.5T and 0.3T, well separated and
      identified in vivo water and fat images covering a broad range of anatomical
      regions have been obtained, supporting the clinical utility of the method.

PMID- 16894579
TI  - Spatial domain method for the design of RF pulses in multicoil parallel
      excitation.
AB  - Parallel excitation has been introduced as a means of accelerating
      multidimensional, spatially-selective excitation using multiple transmit coils,
      each driven by a unique RF pulse. Previous approaches to RF pulse design in
      parallel excitation were either formulated in the frequency domain or restricted
      to echo-planar trajectories, or both. This paper presents an approach that is
      formulated as a quadratic optimization problem in the spatial domain and allows
      the use of arbitrary k-space trajectories. Compared to frequency domain
      approaches, the new design method has some important advantages. It allows for
      the specification of a region of interest (ROI), which improves excitation
      accuracy at high speedup factors. It allows for magnetic field inhomogeneity
      compensation during excitation. Regularization may be used to control integrated
      and peak pulse power. The effects of Bloch equation nonlinearity on the large-tip
      angle excitation error of RF pulses designed with the method are investigated,
      and the utility of Tikhonov regularization in mitigating this error is
      demonstrated.

PMID- 16894580
TI  - Three-dimensional MRI with an undersampled spherical shells trajectory.
AB  - The shells trajectory is a 3D data acquisition method with improved efficiency
      compared to Cartesian sampling. It is a true center-out trajectory that does not
      repeatedly resample the center of k-space, and also offers advantages for motion
      correction. This work demonstrates that k-space undersampling can be combined
      with the shells trajectory to further accelerate the acquisition. The
      undersampling was implemented by removing selected interleaves from shells with
      larger radii. Because only the outer portion of k-space was undersampled, the
      artifacts introduced were of low energy and high spatial frequency. The
      undersampling rate was determined by a Kaiser window with a variable shape
      parameter beta. Various undersampling schemes with different beta values were
      examined. Phantom and volunteer studies demonstrate that when up to a twofold
      acceleration is achieved, only minor artifacts are introduced by undersampling
      the shells trajectory. For a fixed acquisition time, the improved efficiency can
      be used to increase spatial resolution.

PMID- 16894581
TI  - Detrimental effects of BOLD signal in arterial spin labeling fMRI at high field
      strength.
AB  - Arterial spin labeling (ASL) MRI is a useful technique for noninvasive
      measurement of cerebral blood flow (CBF) in humans. High field strength provides
      a unique advantage for ASL because of longer blood T(1) relaxation times, making
      this technique a promising quantitative approach for functional brain mapping.
      However, higher magnetic field also introduces new challenges. Here it is shown
      that the CBF response determined using ASL functional MRI (fMRI) at 3.0 T
      contains significant contamination from blood-oxygenation-level-dependent (BOLD)
      effects. Due to interleaved acquisitions of label and control images, difference
      in blood oxygenation status between these two scans can cause incomplete
      cancellation of the static signal upon image subtraction, resulting in a BOLD
      related artifact in the estimated CBF hemodynamics. If not accounted for, such an
      effect can complicate the interpretation of the ASL results, e.g., causing a
      delayed onset and offset of the response, or inducing an artifactual poststimulus
      undershoot. The BOLD contribution also decreases the sensitivity of ASL-based
      fMRI. Correction methods are proposed to reduce the artifact, giving increased
      number of activated voxels (18+/-5%, P=0.006) and more accurate estimation of CBF
      temporal characteristics.

PMID- 16894583
TI  - Delayed changes in T1-weighted signal intensity in a rat model of 15-minute
      transient focal ischemia studied by magnetic resonance imaging/spectroscopy and
      synchrotron radiation X-ray fluorescence.
AB  - Previous studies have found that rats subjected to 15-min transient middle
      cerebral artery occlusion (MCAO) show neurodegeneration in the dorsolateral
      striatum only, and the resulting striatal lesion is associated with increased T1
      weighted (T1W) signal intensity (SI) and decreased T2-weighted (T2W) SI at 2-8
      weeks after the initial ischemia. It has been shown that the delayed increase in
      T1W SI in the ischemic region is associated with deposition of paramagnetic
      manganese ions. However, it has been suggested that other mechanisms, such as
      tissue calcification and lipid accumulation, also contribute to the relaxation
      time changes. To clarify this issue, we measured changes in relaxation times,
      lipid accumulation, and elemental distributions in the brain of rats subjected to
      15-min MCAO using MRI, in vivo 1H MR spectroscopy (MRS), and synchrotron
      radiation X-ray fluorescence (SRXRF). The results show that a delayed (2 weeks
      after ischemia) increase in T1W SI in the ischemic striatum is associated with
      significant increases in manganese, calcium, and iron, but without evident
      accumulation of MRS-visible lipids or hydroxyapatite precipitation. It was also
      found that 15-min MCAO results in acutely reduced N-acetylaspartate
      (NAA)/creatine (Cr) ratio in the ipsilateral striatum, which recovers to the
      control level at 2 weeks after ischemia.

PMID- 16894582
TI  - Rapid 3D-T1rho mapping of the knee joint at 3.0T with parallel imaging.
AB  - Three-dimensional spin-lattice relaxation time in the rotating frame (3D-T1rho)
      with parallel imaging at 3.0T was implemented on a whole-body clinical scanner. A
      3D gradient-echo sequence with a self-compensating spin-lock pulse cluster was
      combined with generalized autocalibrating partially parallel acquisitions
      (GRAPPA) to acquire T1rho-weighted images. 3D-T1rho maps of an agarose phantom
      and three healthy subjects were constructed using an eight-channel phased-array
      coil without parallel imaging and with parallel imaging acceleration factors of 2
      and 3, in order to assess the reproducibility of the method. The coefficient of
      variation (CV) of the median T1rho of the agarose phantom was 0.44%, which shows
      excellent reproducibility. The reproducibility of in vivo 3D-T1rho maps was also
      investigated in three healthy subjects. The CV of the median T1rho of the
      patellar cartilage varied between approximately 1.1% and 4.3%. Similarly, the CV
      varied between approximately 2.1-5.8%, approximately 1.4-8.7%, and approximately
      1.5-4.1% for the biceps femoris and lateral and medial gastrocnemius muscles,
      respectively. The preliminary results demonstrate that 3D-T1rho maps can be
      constructed with good reproducibility using parallel imaging. 3D-T1rho with
      parallel imaging capability is an important clinical tool for reducing both the
      total acquisition time and RF energy deposition at 3T.

PMID- 16894584
TI  - Low-level laser irradiation modulates matrix metalloproteinase activity and gene
      expression in porcine aortic smooth muscle cells.
AB  - BACKGROUND AND OBJECTIVES: The vascular extracellular matrix is maintained by a
      dynamic balance between matrix synthesis and degradation. This equilibrium is
      disrupted in arterial pathologies such as abdominal aortic aneurysm. Low-level
      laser irradiation (LLLI) promotes wound healing. However, its effect on smooth
      muscle cells (SMCs), a central player in these responses, has not been
      established. The current study was designed to determine the effects of LLLI on
      arterial SMC proliferation, inflammatory markers, and matrix proteins. STUDY
      DESIGN/MATERIALS AND METHODS: Porcine primary aortic SMCs were irradiated with a
      780 nm laser diode (1 and 2 J/cm(2)). Trypan blue exclusion assay,
      immunofluorescent staining for collagen I and III, Sircol assay, gelatin
      zymography, and RT-PCR were used to monitor proliferation; collagen trihelix
      formation; collagen synthesis; matrix metalloproteinase-2 (MMP-2) activity, and
      gene expression of MMP-1, MMP-2, tissue inhibitor of MMP-1 (TIMP-1), TIMP-2, and
      IL-1-beta, respectively. RESULTS: LLLI-increased SMC proliferation by 16 and 22%
      (1 and 2 J/cm(2), respectively) compared to non-irradiated cells (P<0.01 and
      P<0.0005). Immediately after LLLI, trihelices of collagen I and III appeared as
      perinuclear fluorescent rings. Collagen synthesis was increased twofold (2 days
      after LLLI: 14.3+/-3.5 microg, non-irradiated control: 6.6+/-0.7 microg, and TGF
      beta stimulated control: 7.1+/-1.2 microg, P<0.05), MMP-2 activity after LLLI was
      augmented (over non-irradiated control) by 66+/-18% (2 J/cm(2); P<0.05), and MMP
      1 gene expression upregulated. However, TIMP-2 was upregulated, and MMP-2 gene
      expression downregulated. IL-1-beta gene expression was reduced. CONCLUSIONS:
      LLLI stimulates SMC proliferation, stimulates collagen synthesis, modulates the
      equilibrium between regulatory matrix remodeling enzymes, and inhibits pro
      inflammatory IL-1-beta gene expression. These findings may be of therapeutic
      relevance for arterial diseases such as aneurysm where SMC depletion, weakened
      extracellular matrix, and an increase in pro-inflammatory markers are major
      pathologic components.

PMID- 16894585
TI  - Side-firing sealing caps for hollow optical fibers.
AB  - BACKGROUND AND OBJECTIVES: Hollow optical fibers are useful for delivery of high
      energy infrared laser beam such as Er:YAG lasers. We propose side-firing optics
      for hollow optical fibers for laser endoscopic applications mainly in oto-rhino
      laryngology and urology. STUDY DESIGN/MATERIALS AND METHODS: To produce a
      circular beam, cone-shaped caps are designed and caps with slanted end are
      proposed for producing a spot beam in side direction. Both types of caps are
      fabricated by fusing and polished Pyrex and silica glass tubes. RESULTS: For the
      both of the cone-shaped and slanted-end caps effectively deflect laser beam as
      designed and these caps show high durability for Er:YAG laser light with pulse
      energy higher than 100 mJ. CONCLUSIONS: By choosing the proper shape of the cap
      ends, these caps deflect an input laser beam to a preferred direction at low
      insertion losses. By using these side-firing optics, one can easily irradiate the
      inside of tubular organs.

PMID- 16894586
TI  - Shear wave group velocity inversion in MR elastography of human skeletal muscle.
AB  - In vivo quantification of the anisotropic shear elasticity of soft tissue is an
      appealing objective of elastography techniques because elastic anisotropy can
      potentially provide specific information about structural alterations in diseased
      tissue. Here a method is introduced and applied to MR elastography (MRE) of
      skeletal muscle. With this method one can elucidate anisotropy by means of two
      shear moduli (one parallel and one perpendicular to the muscle fiber direction).
      The technique is based on group velocity inversion applied to bulk shear waves,
      which is achieved by an automatic analysis of wave-phase gradients on a
      spatiotemporal scale. The shear moduli are then accessed by analyzing the
      directional dependence of the shear wave speed using analytic expressions of
      group velocities in k-space, which are numerically mapped to real space. The
      method is demonstrated by MRE experiments on the biceps muscle of five
      volunteers, resulting in 5.5+/-0.9 kPa and 29.3+/-6.2 kPa (P<0.05) for the
      medians of the perpendicular and parallel shear moduli, respectively. The
      proposed technique combines fast steady-state free precession (SSFP) MRE
      experiments and fully automated processing of anisotropic wave data, and is thus
      an interesting MRI modality for aiding clinical diagnosis.

PMID- 16894588
TI  - Abnormalities of CSF flow patterns in the cerebral aqueduct in treatment
      resistant late-life depression: a potential biomarker of microvascular
      angiopathy.
AB  - There is growing evidence that microvascular angiopathy (MVA) plays an important
      role in the development of dementia and affective disorders in older people. At
      currently available image resolutions it is not possible to image directly the
      vascular changes associated with MVA, but the effects on blood and cerebrospinal
      fluid (CSF) flow may be detectable. The aim of this study was to investigate a
      potential biomarker for MVA based on MRI of abnormalities in CSF flow. Since
      there is considerable indirect evidence that treatment resistance in late-onset
      depressive disorder is related to MVA, we assessed the method in a group of 22
      normal volunteers and 29 patients with responsive (N=21) or treatment-resistant
      (N=8) late-onset depressive disorder. Single-slice quantified phase-contrast (PC)
      images of cerebral blood and CSF flow were collected at 15 points over a cardiac
      cycle, and the resulting flow curves were parameterized. Significant differences
      in the CSF flow (width of systolic flow peak and diastolic flow volume, both
      P<0.01) through the cerebral aqueduct were observed for the group of treatment
      resistant patients when compared to age matched controls. No significant
      difference was observed for a group of 21 patients with treatment-responsive
      depression. The findings support the hypothesis that MR measurement of CSF flow
      abnormalities provides a biomarker of MVA, and thus could have application in a
      wide range of age-related diseases.

PMID- 16894587
TI  - Global and regional reproducibility of T2 relaxation time measurements in human
      patellar cartilage.
AB  - Seven T2 maps (multiecho (ME) sequence: 3000 ms, eight echoes with 13.2 ms of
      echo spacing, 20 sections) and T1-weighted (T1-w) fast low-angle shot (FLASH
      water excitation (WE)) data sets from four imaging sessions (right patellae of 10
      healthy volunteers) were obtained. A segmentation of cartilage (WE sequence) was
      overlaid on the ME data and T2 values were calculated for total cartilage, three
      layers, three facets (global), and 240 ROIs (regional). Reproducibility
      (precision error) was calculated as the root mean square average (RMSA) of the
      individual coefficients of variation (COVs, %) and standard deviations (SDs, ms)
      for intra- and intersession reproducibility. The precision error was 3-7% and 6
      29% for global and regional T2, respectively. There was no difference between
      intra- and intersession reproducibility, but there was worse reproducibility in
      the superficial layers compared to the deeper layers. Peripheral ROI
      reproducibility (mean=13%) was worse than in the central portions (mean=11%), but
      omission of the periphery did not positively affect the globally calculated T2
      reproducibility. The precision errors were small compared to reported changes in
      diseased cartilage, suggesting good discriminatory power of the technique. Our
      data provide a first estimate of global and regional reproducibility errors of T2
      in healthy cartilage, and may serve as a basis for sample size calculations and
      aid study designs for longitudinal and cross-sectional trials in osteoarthritis
      (OA).

PMID- 16894590
TI  - Future orientation moderates the relationship between functional status and
      suicide ideation in depressed adults.
AB  - Functional impairment might amplify suicide risk in later life. A positive view
      of the future may reduce this risk. We tested the hypothesis that hopelessness
      and positive future orientation moderate the association between functional
      status and suicide ideation in a sample of 136 patients, 55 years of age or
      older, in treatment for depression. Future orientation moderated the association
      between functional status and suicide ideation; hopelessness did not. Although
      prospective research is needed to test more rigorously the hypothesized
      protective role of positive future orientation, our data suggest that treatments
      designed to enhance future orientation might decrease suicide risk.

PMID- 16894589
TI  - Young, adult, and old rats have similar changes in mRNA expression of many
      skeletal genes after fracture despite delayed healing with age.
AB  - Genes active in fracture healing are not well understood. Because age slows
      skeletal repair, the change in gene expression between animals of differing ages
      may illuminate novel pathways important to this healing response. To explore
      this, 6-, 26-, and 52-week-old female Sprague-Dawley rats were subjected to mid
      diaphyseal femoral fracture with intramedullary fixation. The fracture callus was
      collected at 0, 0.4 (3 days), 1, 2, 4, or 6 weeks after fracture. RNA was
      extracted and pooled between two animals for each sample. Three samples were done
      for each time point for each age for a total of 54 Affymetrix U34A GeneChip
      microarrays. Of the 8700 genes on each array, 3300 were scored as present. Almost
      all of these genes were affected by femoral fracture with either upregulation or
      downregulation in the 6 weeks after fracture. Upregulated genes included markers
      for matrix genes for both cartilage and bone, osteoblasts, osteocytes,
      osteoclasts, fibroblasts, and mast cells. Downregulated genes included genes
      related to blood cell synthesis. Nearly all genes presently associated with bone
      metabolism showed the same response to fracture healing regardless of the age of
      the animal. In conclusion, skeletal fracture led to similar changes in RNA
      expression for most skeletal genes despite the delay in the formation of bone to
      bridge the fracture gap in old rats. Defects in the healing of skeletal trauma in
      older rats may lie in systems not normally studied by skeletal biologists.

PMID- 16894591
TI  - Wear and toughness of crosslinked polyethylene for total knee replacements: a
      study using a simulator and small-punch testing.
AB  - Severe loading and complex kinematics in total knee replacement make wear
      performance and toughness of the polyethylene in tibial inserts important. We
      investigated wear of crosslinked polyethylene using a knee simulator and measured
      toughness using small-punch testing. GUR1050 rods were gamma-irradiated in air at
      doses from 0 to 200 kGy, annealed in nitrogen, and machined into tibial inserts.
      The simulator was run to 4 million cycles, and wear rates determined from weight
      loss. Wear rate decreased by 54, 78, and 95% as radiation dose increased from 50
      to 75 to 100 kGy, respectively. At every dose, toughness was significantly less
      after simulator testing, but the difference between control and wear-tested
      polyethylene, considered to be due to fatigue damage accumulation, was smallest
      at 50 kGy. The simulator-tested polyethylene that received 35 to 75 kGy had
      slightly higher toughness than equivalent material that received no irradiation.
      However, the toughness of simulator-tested polyethylene that received 150 and 200
      kGy was lower than that of the simulator-tested polyethylene that received no
      irradiation. Our results suggest that an optimal irradiation dose may exist for
      crosslinked polyethylene for use in TKR and that the optimum dose would be less
      than the 100 kGy or more that are used in some current crosslinked polyethylene
      for hip replacement.

PMID- 16894592
TI  - Changes in lower limb kinematics, kinetics, and muscle activity in subjects with
      functional instability of the ankle joint during a single leg drop jump.
AB  - The purpose of this study was to identify differences in 3D kinematics, kinetics,
      and ankle joint muscle activity in subjects with functional instability (FI) of
      the ankle joint during a drop jump. Twenty-four subjects with the subjective
      complaint of FI of the ankle joint and 24 noninjured control subjects performed
      10 single leg drop jumps onto a force-plate. Timing and magnitude of kinetic
      data, timing of kinematic data, and integrated EMG (IEMG) activity of the rectus
      femoris, peroneus longus, tibialis anterior, and soleus muscles during two 200-ms
      time periods either side of initial contact (IC) with the ground were analyzed
      and compared between groups. Subjects with FI demonstrated a significant decrease
      in pre-IC peroneus longus IEMG activity, which was accompanied by a change in
      frontal plane movement at the ankle joint during the same time period. Following
      IC, FI subjects were less efficient than control group subjects in reaching the
      closed packed position of the ankle joint. Significant differences were seen
      between the groups' time-averaged and peak vertical and sagittal components of
      ground reaction force. The altered pre-IC peroneus longus IEMG and increased
      inversion of the ankle joint observed in FI subjects could help to explain why
      subjects with FI may suffer from inversion injury to their ankle joint when
      subjected to an unanticipated ground contact. The kinematic and kinetic
      differences observed in subjects with FI may lead to repeated injury and damage
      to the supporting structures of the ankle joint.

PMID- 16894593
TI  - Development of partial thickness articular cartilage injury in an ovine model.
AB  - The purpose of this study was to create a controlled partial thickness cartilage
      lesion in a sheep model, and to provide a foundation to study the natural history
      of the progression of this lesion. Twenty-eight sheep divided into four groups
      (1, 12, 24, and 52 weeks, n=7/group) were used in this study. In one stifle, a
      mechanical tool was used to create a 200 microm partial thickness lesion (1.5x1.5
      cm2) on the medial femoral condyle via arthroscopy. Joint fluid was drawn
      presurgery and after euthanasia for analysis of collage II 3/4 C (long) (C2C).
      After euthanasia, the condyle was analyzed by gross appearance, confocal laser
      microscopy (CLM) for cell viability, scanning electronic microscopy (SEM) for
      surface roughness, Artscan for cartilage stiffness, and histology for cartilage
      morphology. The gross appearance of the treated area appeared rough, soft, and
      swollen compared to untreated control over time. CLM demonstrated that the depth
      of cell death increased to 590 microm at 52 weeks after surgery. SEM demonstrated
      that the treated area became more irregular over time. Stiffness of the treated
      area was significantly less than control by 12 weeks after surgery. Histologic
      analysis demonstrated that the 12, 24, and 52 week groups had significantly
      poorer histologic scores than the 1 week group. Joint fluid analysis demonstrated
      that the treatment group at 1 week had significant higher levels of C2C than the
      pretreatment baseline data. The results of this study demonstrated that partial
      thickness injury of cartilage continued to propagate and degenerate over time in
      this sheep model. Options for the prevention or treatment of this lesion may be
      tested using this model in the future.

PMID- 16894594
TI  - Lineage specification in neural crest cell pathfinding.
AB  - There are two principal models to explain neural crest patterning. One assumes
      that neural crest cells are multipotent precursors that migrate throughout the
      embryo and differentiate according to cues present in the local environment. A
      second proposes that the neural crest is a population of cells that becomes
      restricted to particular fates early in its existence and migrates along
      particular pathways dependent on unique cell-autonomous properties. Although it
      is now evident that the neural crest cell population, as a whole, is actually
      heterogenous (composed of both multipotent and restricted progenitors), evidence
      supporting the model of prespecification has increased over the past few years.
      This review will begin by telling the story of melanoblasts: a neural crest
      subpopulation that is biased toward a single fate and subsequently acquires
      intrinsic properties that guide cells of this lineage to their final destination.
      The remainder of this review will explore whether this model is exclusive to
      melanoblasts or if it can also be used to explain the patterning of other neural
      crest cells like those of the sensory, sympathoadrenal, and enteric lineages.

PMID- 16894595
TI  - Linkage disequilibrium, haplotype and association studies of a chromosome 4 GABA
      receptor gene cluster: candidate gene variants for addictions.
AB  - Strong genetic contributions to individual differences in vulnerability to
      addictions are well supported by classical genetic studies. Linkage and
      association genome scans for addiction vulnerability have provided converging
      evidence for several chromosomal regions which are likely to harbor allelic
      variants that contribute to such vulnerability. We and others have delineated a
      candidate addiction-associated chromosome 4p12 "rSA3" region based on convergent
      data from association genome scanning studies in polysubstance abusers [Uhl et
      al. (2001); Am J Hum Genet 69(6):1290-1300], linkage-based studies in alcoholism
      [Long et al. (1998); Am J Med Genet 81(3):216-221; Reich et al. (1998); Am J Med
      Genet 81(3):207-215] and association-based studies for alcoholism and association
      based studies for individual differences in electroencephalographic (EEG)
      spectral power phenotypes [Porjesz et al. (2002); Proc Natl Acad Sci USA
      99(6):3729-3733; Edenberg et al. (2004); Am J Hum Genet 74(4):705-714]. The rSA3
      region contains interesting candidate genes that encode the alpha 2, alpha 4,
      beta 1, and gamma 1 receptor subunits for the principal brain inhibitory
      neurotransmitter, gamma-aminobutyric acid (GABA) [Covault et al. (2004); Am J Med
      Genet Part B 129B:104-109; Edenberg et al. (2004); Am J Hum Genet 74(4):705-714;
      Lappalainen et al. (2005); Alcohol Clin Exp Res 29(4):493-498]. We now report
      assessment of single nucleotide polymorphism (SNP) genotypes in this region in
      three samples of substance abusers and controls. These results delineate the
      haplotypes and patterns of linkage disequilibrium in this region, focus attention
      of the GABRA2 gene and identify modest associations between GABRA2 genotypes and
      addiction phenotypes. These results are consistent with modest roles for GABRA2
      variants in addiction vulnerabilities.

PMID- 16894596
TI  - Prediction of continuous B-cell epitopes in an antigen using recurrent neural
      network.
AB  - B-cell epitopes play a vital role in the development of peptide vaccines, in
      diagnosis of diseases, and also for allergy research. Experimental methods used
      for characterizing epitopes are time consuming and demand large resources. The
      availability of epitope prediction method(s) can rapidly aid experimenters in
      simplifying this problem. The standard feed-forward (FNN) and recurrent neural
      network (RNN) have been used in this study for predicting B-cell epitopes in an
      antigenic sequence. The networks have been trained and tested on a clean data
      set, which consists of 700 non-redundant B-cell epitopes obtained from Bcipep
      database and equal number of non-epitopes obtained randomly from Swiss-Prot
      database. The networks have been trained and tested at different input window
      length and hidden units. Maximum accuracy has been obtained using recurrent
      neural network (Jordan network) with a single hidden layer of 35 hidden units for
      window length of 16. The final network yields an overall prediction accuracy of
      65.93% when tested by fivefold cross-validation. The corresponding sensitivity,
      specificity, and positive prediction values are 67.14, 64.71, and 65.61%,
      respectively. It has been observed that RNN (JE) was more successful than FNN in
      the prediction of B-cell epitopes. The length of the peptide is also important in
      the prediction of B-cell epitopes from antigenic sequences. The webserver ABCpred
      is freely available at www.imtech.res.in/raghava/abcpred/.

PMID- 16894597
TI  - Analysis of axis induction mutant embryos reveals morphogenetic events associated
      with zebrafish yolk extension formation.
AB  - We analyze patterning and morphogenetic events during somitogenesis in hecate
      mutant embryos, which exhibit early axis induction defects. The posterior region,
      in the absence of a dorsal axis, is capable of forming organized gene expression
      patterns. The aberrant morphogenesis of mutant embryos is associated with
      anteriorly directed cell movements, underlying the enveloping layer, from the
      posterior region. In both wild-type and mutant embryos, these changes result in
      an accumulation of cells, whose location correlates with a constriction in the
      posterior yolk cell, which in the wild-type corresponds to the yolk extension.
      The region encompassing the constriction corresponds to a region of expression of
      zangptl2 in the yolk syncytial layer, which expands anteriorly together with the
      anteriorly migrating tail bud-derived cell population. Our data indicate that
      yolk extension formation is associated with coordinated changes involving the
      anterior migration of cells from the posterior region, changes in surface
      cellular layers, and inductive gene expression events in the YSL.

PMID- 16894598
TI  - Critical role of Brg1 member of the SWI/SNF chromatin remodeling complex during
      neurogenesis and neural crest induction in zebrafish.
AB  - Brg1 is a member of the SWI/SNF chromatin-remodeling complex, and in some
      organisms Brg1 has been shown to interact with beta-catenin and positively
      control the TCF/LEF transcription factor that is located downstream of the Wnt
      signal transduction pathway. During development, TCF/LEF activity is critical
      during neurogenesis and head induction. In zebrafish, Brg1-deficient embryos
      exhibit retinal cell differentiation and eye defects; however, the role of Brg1
      in neurogenesis and neural crest cell induction remains elusive. We used
      zebrafish deficient in Brg1 (yng) or Brg1 specific-morpholino oligonucleotide
      mediated knockdown to analyze the embryonic requirements of Brg1. Our results
      indicate that reduction in Brg1 expression leads to the expansion of the
      forebrain-specific transcription factor, six3, and marked reduction in expression
      of the mid/hind-brain boundary and hind-brain genes, engrailed2 and krox20,
      respectively. At 12 hpf, the expression of neural crest specifiers are severely
      affected in Brg1-morpholino-injected embryos. These results suggest that Brg1 is
      involved in neural crest induction, which is critical for the development of
      neurons, glia, pigment cells, and craniofacial structures. Brg1 is a maternal
      factor, and brg1-deficient embryos bearing the yng mutation derived from
      heterozygote intercrosses exhibit lesser effects on neural crest-specific gene
      expression, but show defects in neurogenesis and neural crest cell
      differentiation. This is exhibited by the aberrant brain patterning, a reduction
      in the sensory neurons, and craniofacial defects. These results further elucidate
      the critical role for Brg1 in neurogenesis, neural crest induction, and
      differentiation.

PMID- 16894599
TI  - Expression analysis of IGFBP-rP10, IGFBP-like and Mig30 in early Xenopus
      development.
AB  - To date, five members of the insulin-like growth factor-binding protein (IGFBP)
      superfamily have been described in Xenopus laevis. Here, we report the isolation
      of two new IGFBPs: xIGFBP-rP10, and xIGFBP-like. The proteins share the same
      domain architecture, and together with Mig30, form a subgroup within the IGFBP
      superfamily. Temporal expression analysis shows that they are expressed
      differentially during early development. xIGFBP-rP10 is continuously expressed,
      whereas Mig30 expression peaks during gastrulation. IGFBP-like is expressed from
      neurulation onward. The three genes have characteristic spatial expression
      domains, which overlap in some regions. Both xIGFBP-rP10 and Mig30 are expressed
      on the dorsal side of the embryo during gastrulation. Later, xIGFBP-rP10 is
      expressed in the notochord, the floor plate, the somites, and the fin. xIGFBP
      like expression is seen primarily in the developing central nervous system and
      overlaps with Mig30 expression at the end of neurulation in the developing
      somites and in tail bud stages in the eyes.

PMID- 16894600
TI  - Enhanced sensitivity and stability in two-color in situ hybridization by means of
      a novel chromagenic substrate combination.
AB  - Double in situ hybridization analysis is a fundamental technique for studying the
      expression of two genes with high temporal and spatial resolution. However, due
      to the lack of sensitivity in current detection methods, this approach is
      powerful only when at least one transcript is abundantly expressed. Here, we
      report a new enzyme/chromagenic substrate combination that provides sufficient
      sensitivity for detecting two less abundant transcripts and stability for
      subsequent paraffin sectioning.

PMID- 16894601
TI  - The origin of the diversity of leaf venation pattern.
AB  - The leaf venation pattern of plants shows remarkable diversity and species
      specificity. However, the mechanism underlying the pattern formation and pattern
      diversity remains unclear. We developed a mathematical model that is based on the
      positive feedback regulation between plant hormone auxin and its efflux carrier.
      This system can generate auxin flow pathways by self-organization from an almost
      homogeneous state. This result explains a well-known experimental phenomenon
      referred as to "polar auxin transport." The model can produce diverse leaf
      venation patterns with spatial regularity under similar conditions to those of
      leaf development, that is, in the presence of leaf expansion and auxin sink.
      Final venation patterns are strikingly affected by leaf shape and leaf expansion.
      These results indicate that the positive feedback regulation between auxin and
      its efflux carrier is a central dynamic in leaf venation pattern formation. The
      diversity of leaf venation patterns in plant species is probably due to the
      differences of leaf shape and leaf expansion pattern.

PMID- 16894602
TI  - Better prediction of the location of alpha-turns in proteins with support vector
      machine.
AB  - We have developed a novel method named AlphaTurn to predict alpha-turns in
      proteins based on the support vector machine (SVM). The prediction was done on a
      data set of 469 nonhomologous proteins containing 967 alpha-turns. A great
      improvement in prediction performance was achieved by using multiple sequence
      alignment generated by PSI-BLAST as input instead of the single amino acid
      sequence. The introduction of secondary structure information predicted by
      PSIPRED also improved the prediction performance. Moreover, we handled the very
      uneven data set by combining the cost factor j with the "state-shifting" rule.
      This further promoted the prediction quality of our method. The final SVM model
      yielded a Matthews correlation coefficient (MCC) of 0.25 by a 10-fold cross
      validation. To our knowledge, this MCC value is the highest obtained so far for
      predicting alpha-turns. An online Web server based on this method has been
      developed and can be freely accessed at http://bmc.hust.edu.cn/bioinformatics/ or
      http://210.42.106.80/.

PMID- 16894603
TI  - Maternal expression and function of the Drosophila sox gene Dichaete during
      oogenesis.
AB  - Members of the Sox family of DNA-binding HMG domain proteins have been shown to
      regulate gene transcription in a wide range of developmental processes, including
      sex determination, neurogenesis, and chondrogenesis. However, little is known
      about their potential functions in developing germline tissues. In Drosophila,
      the Sox protein Dichaete (a.k.a., Fish-hook) is a member of the SoxB subgroup
      whose HMG domain shares strong sequence similarity to that of vertebrate Sox2.
      Dichaete exhibits dynamic expression in embryonic and larval stages and has
      pleiotropic functions in a variety of tissues. In this study, we extend analyses
      of Dichaete function and show that expression of Dichaete protein is detected in
      the developing oocyte during early to mid stages of oogenesis. Strikingly,
      Dichaete exhibits cytoplasmic distribution and is not detected in the oocyte
      nucleus. Germline mosaic analyses revealed that the Dichaete gene has maternal
      functions that influence dorsal/ventral patterning of the egg chamber. Dichaete
      mutant eggs exhibit defects in formation of the dorsal appendages,
      differentiation of dorsal/anterior follicle cells, and mislocalization of Gurken
      protein and gurken mRNA. Dichaete protein was shown to possess RNA-binding
      capabilities, suggesting a direct post-transcriptional role in regulating RNA
      functions.

PMID- 16894604
TI  - The molecular setup of the avian head mesoderm and its implication for
      craniofacial myogenesis.
AB  - The head mesoderm is the mesodermal tissue on either side of the brain, from
      forebrain to hindbrain levels, and gives rise to the genuine head muscles. Its
      relatedness to the more posterior paraxial mesoderm, the somites, which generate
      the muscles of the trunk, is conversely debated. To gain insight into the
      molecular setup of the head mesoderm, its similarity or dissimilarity to the
      somitic mesoderm, and the implications of its setup for the progress of muscle
      formation, we investigated the expression of markers (1) for mesoderm
      segmentation and boundary formation, (2) for regional specification and
      somitogenesis and (3) for the positive and negative control of myogenic
      differentiation. We show that the head mesoderm is molecularly distinct from
      somites. It is not segmented; even the boundary to the first somite is ill
      defined. Importantly, the head mesoderm lacks the transcription factors driving
      muscle differentiation while genes suppressing differentiation and promoting cell
      proliferation are expressed. These factors show anteroposteriorly and
      dorsoventrally regionalised but overlapping expression. Notably, expression
      extends into the areas that actively contribute to the heart, overlapping with
      the expression of cardiac markers.

PMID- 16894605
TI  - Changes in gravitational force cause changes in gene expression in the lens of
      developing zebrafish.
AB  - Gravity has been a constant physical factor during the evolution and development
      of life on Earth. We have been studying effects of simulated microgravity on gene
      expression in transgenic zebrafish embryos expressing gfp under the influence of
      gene-specific promoters. In this study, we assessed the effect of microgravity on
      the expression of the heat shock protein 70 (hsp70) gene in lens during
      development using transgenic zebrafish embryos expressing gfp under the control
      of hsp70 promoter/enhancer. Hsp70:gfp expression was up-regulated (45%) compared
      with controls during the developmental period that included the lens
      differentiation stage. This increase was lens specific, because the entire embryo
      showed only a 4% increase in gfp expression. Northern blot and in situ
      hybridization analysis indicated that the hsp70:gfp expression recapitulated
      endogenous hsp70 mRNA expression. Hypergravity exposure also increased hsp70
      expression during the same period. In situ hybridization analysis for two lens
      specific crystallin genes revealed that neither micro- nor hypergravity affected
      the expression level of betaB1-crystallin, a non-hsp gene used as a marker for
      lens differentiation. However, hypergravity changed the expression level of
      alphaA-crystallin, a member of the small hsp gene family. Terminal
      deoxynucleotidyl transferase-mediated deoxyuridinetriphosphate nick end-labeling
      (TUNEL) assay analysis showed that altered-gravity (Deltag) decreased apoptosis
      in lens during the same period and the decrease correlated with the up-regulation
      of hsp70 expression, suggesting that elimination of nuclei from differentiating
      lens fiber cells was suppressed probably through hsp70 up-regulation. These
      results support the idea that Deltag influences hsp70 expression and
      differentiation in lens-specific and developmental period specific manners and
      that hsp family genes play a specific role in the response to Deltag.

PMID- 16894606
TI  - High-resolution ultrasound analysis of subsynovial connective tissue in human
      cadaver carpal tunnel.
AB  - The carpal tunnel contains the median nerve, nine flexor tendons, two synovial
      bursae, and peritendinous subsynovial connective tissue (SSCT). Fibrosis of the
      SSCT is the most consistent pathological finding in patients with carpal tunnel
      syndrome. We investigated the anatomy and gliding characteristics of the flexor
      digitorum superficialis tendon and its adjacent SSCT with high-resolution
      ultrasound (15 MHz). Our hypotheses were that tendon and SSCT are distinguishable
      by ultrasound and that their velocities during tendon excursion are different.
      Qualitative ultrasound analysis of a flexor tendon and its SSCT was performed on
      five cadaver wrists and correlated to respective findings after anatomical study
      of the same cadavers. Quantitative Doppler velocity analysis of eight cadaver
      wrists was done to assess the sliding movement of the tendon and its SSCT within
      the carpal tunnel. No significant difference was found between the thickness of
      SSCT measured by ultrasound and that measured directly after dissection. The SSCT
      moved slower than its flexor tendon. The SSCT velocities were statistically
      different from the tendon velocities (t-test, p>0.001). High-resolution
      ultrasound is a very precise method to display the anatomy of the tendon and SSCT
      within the carpal tunnel, and their different velocities can be detected with
      Doppler. Noninvasive assessment of the thickness and velocity of the tenosynovium
      in carpal tunnel syndrome by high-resolution sonography might be a new diagnostic
      tool for disorders affecting the SSCT, especially carpal tunnel syndrome.

PMID- 16894607
TI  - Structures of soluble amyloid oligomers from computer simulations.
AB  - Alzheimer's, Parkinson's, and Creutzfeldt-Jakob's neurodegenerative diseases are
      all linked with the assembly of normally soluble proteins into amyloid fibrils.
      Because of experimental limitations, structural characterization of the soluble
      oligomers, which form early in the process of fibrillogenesis and are cytotoxic,
      remains to be determined. In this article, we study the aggregation paths of
      seven chains of the shortest amyloid-forming peptide, using an activitated method
      and a reduced atomic representation. Our simulations show that disordered KFFE
      monomers ultimately form three distinct topologies of similar energy: amorphous
      oligomers, incomplete rings with beta-barrel character, and cross-beta-sheet
      structures with the meridional but not the equatorial X-ray fiber reflections.
      The simulations also shed light on the pathways from misfolded aggregates to
      fibrillar-like structures. They also underline the multiplicity of building
      blocks that can lead to the formation of the critical nucleus from which rapid
      growth of the fibril occurs.

PMID- 16894608
TI  - Kinetics of tamoxifen-regulated Cre activity in mice using a cartilage-specific
      CreER(T) to assay temporal activity windows along the proximodistal limb
      skeleton.
AB  - Cartilage differentiation occurs over a broad time range from early embryonic
      development, when the mesenchymal condensations that give rise to cartilage
      models for future bone first appear, and continuing through adult life, when
      there is ongoing maintenance of articular joint surfaces and re-activation of
      cartilage formation after fracture. The chondrogenic response also figures in the
      pathogenesis of degenerative and inflammatory joint diseases. We have generated a
      transgenic line expressing tamoxifen-dependent Cre recombinase that gives
      efficient recombination in the chondrogenic lineage, both during embryogenesis
      and postnatally, and provides a valuable tool for analysis of gene function
      selectively in chondrogenic cells using conditional genetic approaches. Because
      the cartilage model of the limb skeleton forms progressively in a proximodistal
      order during discrete, well-defined time periods, evaluation of the spatial
      extent of tamoxifen-induced recombination along the limb axis during these time
      windows has also enabled us to examine the pharmacokinetics of single-dose
      tamoxifen injections during pregnancy.

PMID- 16894611
TI  - Crystal structures of the PLP- and PMP-bound forms of BtrR, a dual functional
      aminotransferase involved in butirosin biosynthesis.
AB  - The aminotransferase (BtrR), which is involved in the biosynthesis of butirosin,
      a 2-deoxystreptamine (2-DOS)-containing aminoglycoside antibiotic produced by
      Bacillus circulans, catalyses the pyridoxal phosphate (PLP)-dependent
      transamination reaction both of 2-deoxy-scyllo-inosose to 2-deoxy-scyllo
      inosamine and of amino-dideoxy-scyllo-inosose to 2-DOS. The high-resolution
      crystal structures of the PLP- and PMP-bound forms of BtrR aminotransferase from
      B. circulans were solved at resolutions of 2.1 A and 1.7 A with R(factor)/R(free)
      values of 17.4/20.6 and 19.9/21.9, respectively. BtrR has a fold characteristic
      of the aspartate aminotransferase family, and sequence and structure analysis
      categorises it as a member of SMAT (secondary metabolite aminotransferases)
      subfamily. It exists as a homodimer with two active sites per dimer. The active
      site of the BtrR protomer is located in a cleft between an alpha helical N
      terminus, a central alphabetaalpha sandwich domain and an alphabeta C-terminal
      domain. The structures of the PLP- and PMP-bound enzymes are very similar;
      however BtrR-PMP lacks the covalent bond to Lys192. Furthermore, the two forms
      differ in the side-chain conformations of Trp92, Asp163, and Tyr342 that are
      likely to be important in substrate selectivity and substrate binding. This is
      the first three-dimensional structure of an enzyme from the butirosin
      biosynthesis gene cluster.

PMID- 16894609
TI  - Endogenous bone morphogenetic protein antagonists regulate mammalian neural crest
      generation and survival.
AB  - We demonstrate here that Chordin and Noggin function as bone morphogenetic
      protein (BMP) antagonists in vivo to promote mammalian neural crest development.
      Using Chrd and Nog single and compound mutants, we find that Noggin has a major
      role in promoting neural crest formation, in which Chordin is partially
      redundant. BMP signaling is increased in dorsal tissues lacking Noggin and is
      further increased when Chordin is also absent. The early neural crest domain is
      expanded with decreased BMP antagonism in vivo. Noggin and Chordin also regulate
      subsequent neural crest cell emigration from the neural tube. However, reduced
      levels of these BMP antagonists ultimately result in perturbation of neural crest
      cell derived peripheral nervous system and craniofacial skeletal elements. Such
      defects reflect, at least in part, a function to limit apoptosis in neural crest
      cells. Noggin and Chordin, therefore, function together to regulate both the
      generation and survival of neural crest cells in mammalian development.

PMID- 16894612
TI  - Mouse development: from black eyes to knockouts.

PMID- 16894610
TI  - Regulation of the neurofibromatosis 2 gene promoter expression during embryonic
      development.
AB  - Mutations in the Neurofibromatosis 2 (NF2) gene are associated with
      predisposition to vestibular schwannomas, spinal schwannomas, meningiomas, and
      ependymomas. Presently, how NF2 is expressed during embryonic development and in
      the tissues affected by neurofibromatosis type 2 (NF2) has not been well defined.
      To examine NF2 expression in vivo, we generated transgenic mice carrying a 2.4-kb
      NF2 promoter driving beta-galactosidase (beta-gal) with a nuclear localization
      signal. Whole-mount embryo staining revealed that the NF2 promoter directed beta
      gal expression as early as embryonic day E5.5. Strong expression was detected at
      E6.5 in the embryonic ectoderm containing many mitotic cells. beta-gal staining
      was also found in parts of embryonic endoderm and mesoderm. The beta-gal staining
      pattern in the embryonic tissues was corroborated by in situ hybridization
      analysis of endogenous Nf2 RNA expression. Importantly, we observed strong NF2
      promoter activity in the developing brain and in sites containing migrating cells
      including the neural tube closure, branchial arches, dorsal aorta, and paraaortic
      splanchnopleura. Furthermore, we noted a transient change of NF2 promoter
      activity during neural crest cell migration. While little beta-gal activity was
      detected in premigratory neural crest cells at the dorsal ridge region of the
      neural fold, significant activity was seen in the neural crest cells already
      migrating away from the dorsal neural tube. In addition, we detected considerable
      NF2 promoter activity in various NF2-affected tissues such as acoustic ganglion,
      trigeminal ganglion, spinal ganglia, optic chiasma, the ependymal cell-containing
      tela choroidea, and the pigmented epithelium of the retina. The NF2 promoter
      expression pattern during embryogenesis suggests a specific regulation of the NF2
      gene during neural crest cell migration and further supports the role of merlin
      in cell adhesion, motility, and proliferation during development.

PMID- 16894613
TI  - Effects of dextromethorphan on in vitro contractile responses of mouse and rat
      urinary bladders.
AB  - PURPOSE: Dextromethorphan (DXM) is a cough-suppressing ingredient in a variety of
      over-the-counter cough and cold medications. Dextromethorphan elevates the
      threshold for coughing primarily through a central mechanism. At doses
      recommended for treating coughs the drug is safe and effective. At much higher
      doses, DXM produces dissociative effects similar to those of phencyclidine and
      ketamine. Opioid analgesics structurally related to DXM also inhibit bladder
      contractions and produce urinary retention through a non-opioid mechanism. This
      study evaluated the direct effects of DXM on in vitro contractile responses of
      rat and mouse urinary bladders. METHODS: Male rats and mice were anaesthetized
      and their bladders removed. Bladder strips were suspended in 15 ml oxygenated
      Tyrode's solution containing glucose. Bladder strip contractions were evoked by
      field stimulation (FS), carbachol or elevated KCl concentrations and contractile
      responses recorded. The strips were then exposed to 3 microM (DXM) for 30 min and
      re-stimulated. This sequence was repeated at 10, 30, and 100 microM DXM. RESULTS:
      (a) The rat bladder generated significantly greater tension than the mouse
      bladder. (b) Dextromethorphan produced a dose-dependent inhibition of the
      response to FS that was approximately equal for rat and mouse bladders. FS at 8
      or 32 Hz was significantly more sensitive to DXM inhibition than 2 Hz. (c) The
      response to carbachol was more sensitive to inhibition by DXM than the responses
      to FS or KCl. CONCLUSIONS: These results demonstrate that DXM inhibits bladder
      contractions in vitro and that mouse and rat bladders are affected to
      approximately the same extent.

PMID- 16894614
TI  - Pooled association genome scanning for alcohol dependence using 104,268 SNPs:
      validation and use to identify alcoholism vulnerability loci in unrelated
      individuals from the collaborative study on the genetics of alcoholism.
AB  - Association genome scanning can identify markers for the allelic variants that
      contribute to vulnerability to complex disorders, including alcohol dependence.
      To improve the power and feasibility of this approach, we report validation of
      "100k" microarray-based allelic frequency assessments in pooled DNA samples. We
      then use this approach with unrelated alcohol-dependent versus control
      individuals sampled from pedigrees collected by the Collaborative Study on the
      Genetics of Alcoholism (COGA). Allele frequency differences between alcohol
      dependent and control individuals are assessed in quadruplicate at 104,268
      autosomal SNPs in pooled samples. One hundred eighty-eight SNPs provide (1) the
      largest allele frequency differences between dependent versus control
      individuals; (2) t values >or= 3 for these differences; and (3) clustering, so
      that 51 relatively small chromosomal regions contain at least three SNPs that
      satisfy criteria 1 and 2 above (Monte Carlo P = 0.00034). These positive SNP
      clusters nominate interesting genes whose products are implicated in cellular
      signaling, gene regulation, development, "cell adhesion," and Mendelian
      disorders. The results converge with linkage and association results for alcohol
      and other addictive phenotypes. The data support polygenic contributions to
      vulnerability to alcohol dependence. These SNPs provide new tools to aid the
      understanding, prevention, and treatment of alcohol abuse and dependence.

PMID- 16894615
TI  - Rank information: a structure-independent measure of evolutionary trace quality
      that improves identification of protein functional sites.
AB  - Protein functional sites are key targets for drug design and protein engineering,
      but their large-scale experimental characterization remains difficult. The
      evolutionary trace (ET) is a computational approach to this problem that has been
      useful in a variety of case studies, but its proteomic scale application is
      partially hindered because automated retrieval of input sequences from databases
      often includes some with errors that degrade functional site identification. To
      recognize and purge these sequences, this study introduces a novel and structure
      free measure of ET quality called rank information (RI). It is shown that RI
      decreases in response to errors in sequences, alignments, or functional
      classifications. Conversely, an automated procedure to increase RI by selectively
      removing sequences improves functional site identification so as to nearly match
      manually curated traces in kinases and in a test set of 79 diverse proteins. Thus
      we conclude that RI partially reflects the evolutionary consistency of sequence,
      structure, and function. In practice, as the size of the proteome continues to
      grow exponentially, it provides a novel and structure-free measure of ET quality
      that increases its accuracy for large-scale automated annotation of protein
      functional sites.

PMID- 16894616
TI  - The tension free vaginal tape operation for women with mixed incontinence: Do
      preoperative variables predict the outcome?
AB  - AIMS: The aims of our study were (1) to investigate subjective and objective
      outcomes after tension free vaginal tape (TVT) operations in mixed incontinent
      women, (2) to detect if preoperative subjective and objective variables predict
      the outcome, and (3) to evaluate whether the surgical outcome is different for
      women who preoperatively find stress incontinence, urge incontinence, or urge and
      stress incontinence equally the predominant bother. METHODS: A prospective cohort
      study was performed on 450 mixed incontinent women. A short-form disease-specific
      validated questionnaire, 24-hr pad test, standardized stress test, residual
      urine, and maximum urinary flow were used before and after a TVT operation.
      "Cure" was defined as a condition where the women were very satisfied with the
      TVT operation and had negative stress- and 24 hr pad tests. RESULTS:
      Preoperatively 69% had stress incontinence, 7% urge incontinence, and 24% urge
      and stress incontinence equally as the predominant bother. Cure rates were 80%,
      52%, and 60%, respectively, in these groups. Postoperatively 43% of the women had
      no urge incontinence, while 49% were less, and only 8% were more bothered by urge
      incontinence. A higher preoperative urge incontinence index was correlated with
      significantly higher postoperative bother for all indices and leakage during 24
      hr pad test. CONCLUSIONS: Mixed incontinent women with predominant stress
      incontinence had a better cure rate than those with predominant urge incontinence
      and those who were equally bothered by urge and stress incontinence. This point
      needs to be addressed when informing mixed incontinent women before a TVT
      operation.

PMID- 16894617
TI  - Exploring the relationship between funneled energy landscapes and two-state
      protein folding.
AB  - It should take an astronomical time span for unfolded protein chains to find
      their native state based on an unguided conformational random search. The
      experimental observation that folding is fast can be rationalized by assuming
      that protein energy landscapes are sloped towards the native state minimum, such
      that rapid folding can proceed from virtually any point in conformational space.
      Folding transitions often exhibit two-state behavior, involving extensively
      disordered and highly structured conformers as the only two observable kinetic
      species. This study employs a simple Brownian dynamics model of "protein
      particles" moving in a spherically symmetrical potential. As expected, the
      presence of an overall slope towards the native state minimum is an effective
      means to speed up folding. However, the two-state nature of the transition is
      eradicated if a significant energetic bias extends too far into the non-native
      conformational space. The breakdown of two-state cooperativity under these
      conditions is caused by a continuous conformational drift of the unfolded
      proteins. Ideal two-state behavior can only be maintained on surfaces exhibiting
      large regions that are energetically flat, a result that is supported by other
      recent data in the literature (Kaya and Chan, Proteins: Struct Funct Genet
      2003;52:510-523). Rapid two-state folding requires energy landscapes exhibiting
      the following features: (i) A large region in conformational space that is
      energetically flat, thus allowing for a significant degree of random sampling,
      such that unfolded proteins can retain a random coil structure; (ii) a trapping
      area that is strongly sloped towards the native state minimum.

PMID- 16894618
TI  - A substitution matrix for structural alphabet based on structural alignment of
      homologous proteins and its applications.
AB  - Analysis of protein structures based on backbone structural patterns known as
      structural alphabets have been shown to be very useful. Among them, a set of 16
      pentapeptide structural motifs known as protein blocks (PBs) has been identified
      and upon which backbone model of most protein structures can be built. PBs allows
      simplification of 3D space onto 1D space in the form of sequence of PBs. Here,
      for the first time, substitution probabilities of PBs in a large number of
      aligned homologous protein structures have been studied and are expressed as a
      simplified 16 x 16 substitution matrix. The matrix was validated by benchmarking
      how well it can align sequences of PBs rather like amino acid alignment to
      identify structurally equivalent regions in closely or distantly related proteins
      using dynamic programming approach. The alignment results obtained are very
      comparable to well established structure comparison methods like DALI and STAMP.
      Other interesting applications of the matrix have been investigated. We first
      show that, in variable regions between two superimposed homologous proteins, one
      can distinguish between local conformational differences and rigid-body
      displacement of a conserved motif by comparing the PBs and their substitution
      scores. Second, we demonstrate, with the example of aspartic proteinases, that
      PBs can be efficiently used to detect the lobe/domain flexibility in the
      multidomain proteins. Lastly, using protein kinase as an example, we identify
      regions of conformational variations and rigid body movements in the enzyme as it
      is changed to the active state from an inactive state.

PMID- 16894619
TI  - A double-blind study of the efficacy of venlafaxine extended-release, paroxetine,
      and placebo in the treatment of panic disorder.
AB  - To date, no large-scale, controlled trial comparing a serotonin-norepinephrine
      reuptake inhibitor and selective serotonin reuptake inhibitor with placebo for
      the treatment of panic disorder has been reported. This double-blind study
      compares the efficacy of venlafaxine extended-release (ER) and paroxetine with
      placebo. A total of 664 nondepressed adult outpatients who met DSM-IV criteria
      for panic disorder (with or without agoraphobia) were randomly assigned to 12
      weeks of treatment with placebo or fixed-dose venlafaxine ER (75 mg/day or 150
      mg/day), or paroxetine 40 mg/day. The primary measure was the percentage of
      patients free from full-symptom panic attacks, assessed with the Panic and
      Anticipatory Anxiety Scale (PAAS). Secondary measures included the Panic Disorder
      Severity Scale, Clinical Global Impressions--Severity (CGI-S) and--Improvement
      (CGI-I) scales; response (CGI-I rating of very much improved or much improved),
      remission (CGI-S rating of not at all ill or borderline ill and no PAAS full
      symptom panic attacks); and measures of depression, anxiety, phobic fear and
      avoidance, anticipatory anxiety, functioning, and quality of life. Intent-to
      treat, last observation carried forward analysis showed that mean improvement on
      most measures was greater with venlafaxine ER or paroxetine than with placebo. No
      significant differences were observed between active treatment groups. Panic-free
      rates at end point with active treatment ranged from 54% to 61%, compared with
      35% for placebo. Approximately 75% of patients given active treatment were
      responders, and nearly 45% achieved remission. The placebo response rate was
      slightly above 55%, with remission near 25%. Adverse events were mild or moderate
      and similar between active treatment groups. Venlafaxine ER and paroxetine were
      effective and well tolerated in the treatment of panic disorder.

PMID- 16894621
TI  - The effect of tamoxifen on bladder functions and histology, and the role of
      estrogen receptor beta in a rat chemical cystitis model.
AB  - AIMS: The purpose of this study was to investigate the effect of tamoxifen
      citrate on bladder functions and histology, and also to investigate the role of
      estrogen receptor beta (ER beta) in a rat chemical cystitis model. METHODS: The
      study included 37 female Sprague-Dawley rats. Chemical cystitis was induced by
      intravesical instillation of hydrochloric acid in 32 rats, and the treatment
      group (n = 15) received daily 0.4 mg/kg of tamoxifen citrate with orogastric
      tube, and the control group (n = 17) received no treatment. The sham group
      consisted of five rats having no acid instillation and no treatment. Cystometric
      studies were performed in all rats at the beginning and end of the experiment.
      The rats were euthanized at 2 months. The bladders were removed and examined
      histologically for mast cells, inflammatory cells, and ER beta. RESULTS: The mean
      maximal bladder volume increased by 73.6% +/- 25.2 in the treatment group and
      decreased by 7.2% +/- 10.8 in the control group, revealing a significant
      difference (P = 0.007). The mean bladder compliance increased by 81.2% +/- 25.2
      in the treatment group and decreased by 4.8% +/- 12.7 in the control group,
      revealing a significant difference between the two groups (P = 0.005). ER beta
      positive cells were significantly lower in the bladders with chronic cystitis
      than in the sham group (P = 0.038). CONCLUSIONS: Tamoxifen citrate may be an
      alternative choice, as easy, to other treatment options in the treatment of
      chronic inflammatory condition to improve deteriorated bladder function. In
      addition, ER beta may have a role on chronic bladder inflammation in a rat
      chemical cystitis model.

PMID- 16894620
TI  - Uroselectivity in male dogs of silodosin (KMD-3213), a novel drug for the
      obstructive component of benign prostatic hyperplasia.
AB  - AIMS: Our main aim was to compare the prostatic selectivity of silodosin with
      that of other alpha(1)-adrenoceptor (AR) antagonists. METHODS: We examined
      uroselectivities in two sets of experiments namely, in vitro and in vivo
      functional studies using male dogs. In the in vitro study, after evaluating the
      inhibitory effects of silodosin on noradrenaline (NA)-induced contractions in the
      isolated prostate and isolated carotid artery using the Magnus method, we
      calculated prostatic selectivity. In the in vivo study, we examined the effects
      of drugs on the hypogastric nerve stimulation (HNS)-induced increase in
      intraurethral pressure (IUP) and on blood pressure. The uroselectivity of
      silodosin was compared with those of tamsulosin and naftopidil. RESULTS: In
      vitro, all drugs antagonized NA-induced contraction in both prostate and carotid
      artery. The prostatic selectivity of silodosin (79.4) was much higher than those
      of tamsulosin (1.78), naftopidil (0.55), BMY 7378 (0.115), and prazosin (0.01).
      In vivo, intravenously (i.v.) administered silodosin dose-dependently inhibited
      the HNS-induced increase in IUP with much less hypotensive effect than either
      tamsulosin or naftopidil, the uroselectivity (ED(15)/ID(50)) of silodosin (237)
      being significantly higher than those of tamsulosin (1.21) and naftopidil (2.65).
      CONCLUSIONS: Our results clearly demonstrate that silodosin is a potent and
      highly selective alpha(1A)-AR antagonist. A selective alpha(1A)-AR antagonist
      such as silodosin may have good potential as a less-hypotensive drug for the
      treatment of urinary dysfunction in benign prostatic hyperplasia patients.

PMID- 16894622
TI  - Anteroposterior patterning in the limb and digit specification: contribution of
      mouse genetics.
AB  - The limb has been a privileged object of investigation and reflection for
      scientists over the past two centuries and continues to provide a heuristic
      framework to analyze vertebrate development. Recently, accumulation of new data
      has significantly changed our view on the mechanisms of limb patterning, in
      particular along the anterior-posterior axis. These data have led us to revisit
      the mode of action of the zone of polarizing activity. They shed light on the
      molecular and cellular mechanisms of patterning linked to the Shh-Gli3 signaling
      pathway and give insights into the mechanism of activation of these cardinal
      factors, as well as the consequences of their activity. These new data are in
      good part the result of systematic Application of tools used in contemporary
      mouse molecular genetics. These have extended the power of mouse genetics by
      introducing mutational strategies that allow fine-tuned modulation of gene
      expression, interchromosomal deletions and duplication. They have even made the
      mouse embryo amenable to cell lineage analysis that used to be the realm of chick
      embryos. In this review, we focus on the data acquired over the last five years
      from the analysis of mouse limb development and discuss new perspectives opened
      by these results.

PMID- 16894623
TI  - A review and re-evaluation of an association between the NOTCH4 locus and
      schizophrenia.
AB  - This work reviewed all the reports on the NOTCH4 gene in schizophrenia, which
      have been published since the gene was found to be associated with illness among
      a British population in 2000. The results from independent studies were
      inconsistent. Allelic heterogeneity, clinical diagnosis, ethnical backgrounds,
      and linkage disequilibrium (LD) structures in the human genome may be major
      reasons for poor replication. A couple of studies suggested that the NOTCH4 gene
      could play a role in a subgroup of the disease, such as early-onset schizophrenia
      and negative symptoms. A single study revealed a weak association of the NOTCH4
      gene with frontal lobe brain volumes and a strong association with frontal lobe
      cognitive performance. A meta-analysis showed stronger evidence of the NOTCH4
      association in family-based studies than in case-control studies. In a previous
      study, we found that rs520692, a single nucleotide polymorphism (SNP) at the
      NOTCH4 locus, was associated with schizophrenia in a Chinese population. In the
      present study, we applied a large sample size to re-evaluate our initial findings
      and then confirmed the rs520692 association with illness. The pairwise measures
      did not show strong LD between paired SNPs although the SNPs tested are located
      within a 34-kb region, suggesting that LD within the NOTCH4 gene has been broken
      rapidly by historical recombination in the Chinese population. Taken together,
      the NOTCH4 gene may be associated with schizophrenia but how the gene contributes
      to the etiology of the illness needs a further investigation.

PMID- 16894624
TI  - Intrauterine death, fetal malformation, and delayed pregnancy in Ljungan virus
      infected mice.
AB  - BACKGROUND: A picornavirus (Ljunganvirus [LV]) has recently been associated with
      disease during pregnancy in its natural rodent reservoir and in humans. A study
      of laboratory mice infected under controlled conditions was therefore undertaken.
      METHODS: CD-1 female mice were infected gestational day two and subjected to
      varying regimes of stress. RESULTS: LV infection in combination with stress
      resulted in uterine resorptions, malformations, and neonatal death. A short delay
      in time to first pregnancy and births was observed in pairs infected in utero.
      CONCLUSIONS: LV is found in different species of native animals in both Europe
      and the United States and human epidemiological evidence connects LV and human
      reproduction, while the observations here indicate that LV is responsible for
      reproductive problems in a laboratory mouse model. The current findings suggest
      that the hypothesis that LV also causes disease in pregnant women and their
      offspring deserves further study.

PMID- 16894625
TI  - Microarray analysis of Tbx5-induced genes expressed in the developing heart.
AB  - Tbx5 is a member of the T-box family of transcription factors and is associated
      with Holt-Oram syndrome (HOS), a congenital disorder characterized by heart and
      limb defects. Although implicated in several processes during development, only a
      few genes regulated by Tbx5 have been reported. To identify candidate genes
      regulated by Tbx5 during heart development, a microarray approach was used. A
      cardiac-derived mouse cell line (1H) was infected with adenoviruses expressing
      Tbx5 or beta-galactosidase and RNA was isolated for analysis using an Affymetrix
      gene chip representing over 39,000 transcripts. Real-time reverse transcriptase
      polymerase chain reaction confirmed Tbx5 induction of a subset of the genes,
      including nppa, photoreceptor cadherin, brain creatine kinase, hairy/enhancer-of
      split related 2, and gelsolin. In situ hybridization analysis indicated
      overlapping expression of these genes with tbx5 in the embryonic mouse heart. In
      addition, the effect of HOS-associated mutations on the ability of Tbx5 to induce
      target gene expression was evaluated. Together, these data identify several genes
      induced by Tbx5 that are potentially important during cardiac development. These
      genes represent new candidate gene targets of Tbx5 that may be related to
      congenital heart malformations associated with HOS.

PMID- 16894627
TI  - Three-dimensional slice cultures from murine fetal gut for investigations of the
      enteric nervous system.
AB  - Three-dimensional intestinal cultures offer new possibilities for the examination
      of growth potential, analysis of time specific gene expression, and spatial
      cellular arrangement of enteric nervous system in an organotypical environment.
      We present an easy to produce in vitro model of the enteric nervous system for
      analysis and manipulation of cellular differentiation processes. Slice cultures
      of murine fetal colon were cultured on membrane inserts for up to 2 weeks without
      loss of autonomous contractility. After slice preparation, cultured tissue
      reorganized within the first days in vitro. Afterward, the culture possessed more
      than 35 cell layers, including high prismatic epithelial cells, smooth muscle
      cells, glial cells, and neurons analyzed by immunohistochemistry. The contraction
      frequency of intestinal slice culture could be modulated by the neurotransmitter
      serotonin and the sodium channel blocker tetrodotoxin. Coculture experiments with
      cultured neurospheres isolated from enhanced green fluorescent protein (eGFP)
      transgenic mice demonstrated that differentiating eGFP-positive neurons were
      integrated into the intestinal tissue culture. This slice culture model of
      enteric nervous system proved to be useful for studying cell-cell interactions,
      cellular signaling, and cell differentiation processes in a three-dimensional
      cell arrangement.

PMID- 16894626
TI  - MEKK4 regulates developmental EMT in the embryonic heart.
AB  - Congenital heart malformations occur at a rate of one per one hundred births and
      are considered the most frequent birth defects. This high incidence of cardiac
      defects underscores the complex developmental processes required to form the
      first functioning organ in mammals. The molecular cues which govern heart
      development are poorly defined and require an improved understanding in order to
      advance repair strategies for heart defects. The cytoplasmic MAP kinase kinase
      kinase, MEKK4, is a critical effector in cellular stress responses; however, the
      function of MEKK4 during embryonic development and cardiogenesis is not well
      understood. We have identified MEKK4 as a critical signaling molecule during
      cardiovascular development. We report the detection of MEKK4 transcripts to early
      myocardium, endocardium and to cardiac cushion cells that have executed
      epithelial to mesenchymal transformation (EMT). These observations suggest that
      MEKK4 may function during production of the cushion mesenchyme as required to
      create valves and the septated heart. We used a kinase inactive form of
      MEKK4(MEKK4(KI)) in an in vitro assay that recapitulates in vivo EMT, and show
      that MEKK4(KI) attenuates mesenchyme production. However, addition of a
      constitutively active MEKK4 into ventricular explants, a system that does not
      normally undergo EMT, is not able to cause mesenchymal cell outgrowth. Thus, the
      kinase activity of MEKK4 is essential, but not sufficient, to support
      developmental EMT. This knowledge provides a basis to understand how MEKK4 may
      integrate signaling cascades controlling heart development.

PMID- 16894628
TI  - Electroporation and EGFP labeling of gastrulating quail embryos.
AB  - Labeling embryonic cells to trace their motion is a classical experimental
      approach with a host of techniques being used to mark live cells and tissues.
      Genetically engineered fluorescent protein vectors (DNA plasmids) are a recent
      technology well suited to time-resolved studies of cellular motion in live
      embryos. DNA plasmids encoding fluorescent proteins can be introduced into cells
      using several methods, including electroporation, a technique used widely for
      analysis of tissue culture and embryonic cells. Here we describe a technique
      designed to introduce DNA plasmids into early gastrulation stage quail embryos,
      ex ovo. The method is effective, and with practice enables an investigator to
      direct the vectors to relatively confined regions of gastrulating embryos. The
      required electroporation chamber can be fabricated from common laboratory
      materials. We anticipate that using this method of labeling cells in a warm
      blooded embryo, during gastrulation, will be a fruitful means of studying
      subsequent embryogenesis.

PMID- 16894629
TI  - Morphological and molecular course of mitochondrial pathology in cultured human
      cells exposed long-term to Zidovudine.
AB  - Long-term use of antiretroviral nucleoside reverse transcriptase inhibitors
      (NRTIs) as therapy for human immunodeficiency virus-1 (HIV-1) infection is
      limited by mitochondrial toxicity. Here we document mitochondrial pathology
      during the long-term culture of human HeLa cells in the presence or absence of
      the NRTI Zidovudine(R) (AZT, 800 muM) for up to 77-passages (p), with samples
      taken at early (p5-p11), middle (p36 and p37), and late (p70-p77) passages.
      Samples were analyzed for changes in mitochondrial morphology, mitochondrial
      (mt)DNA quantity, nuclear and mitochondrial gene expression, and mitochondrial
      membrane potential. Mitochondria showed abnormal proliferation at p5 and abnormal
      morphology >/=p36. mtDNA quantity was increased at p5 and p11, and 65% depleted
      at p71. Hierarchical clustering of nuclear gene expression, examined at p37 by
      the NCI cDNA microarray in AZT-exposed cells, showed down-regulation of 13 out of
      16 lipid-metabolizing genes, and up-regulation of most oxidative phosphorylation
      (OXPHOS) genes. OXPHOS genes encoded by mtDNA, examined at p5, p36, and p75 using
      the Mitochondrial Gene Mini Array, revealed up-regulation of genes coding for
      polypeptides of NADH dehydrogenase, ATP synthase, and cytochrome c oxidase.
      Mitochondrial membrane potential, monitored by JC1 staining, was elevated at p10
      and p32, and essentially completely absent at p71. The data show that during
      chronic exposure of HeLa cells to AZT, a compensatory response was induced at the
      earlier passages (p5-p37), and by p71 there was widespread mitochondrial
      morphological damage, severe mtDNA depletion, and a substantial loss of
      mitochondrial membrane potential.

PMID- 16894630
TI  - Application of a continuous bioreactor cascade to study the effect of linoleic
      acid on hybridoma cell physiology.
AB  - The aim of the present study is to demonstrate the use of controlled bioreactors
      for toxicological studies. As a model system the effect of linoleic acid on
      hybridoma cells is studied in two well-controlled continuously operated
      bioreactors placed in series. In the first reactor the effect on rapid
      proliferating cells can be studied, while in the second reactor a special steady
      state is created, which allows studying the effect on apoptotic cells.
      Experiments are done at 0, 25, and 50 microM linoleic acid. At the end of the
      experiment with 50 microM linoleic acid, the concentration of linoleic acid is
      increased stepwise to determine the cytotoxic level. For rapid proliferating
      cells exposed to 25 and 50 microM stimulation of growth was observed. At 50
      microM there was at the same time an increase in cell death through apoptosis.
      For stressed apoptotic cells linoleic acid caused partial growth inhibition at 25
      and 50 microM and arrest of cell proliferation in the G(2)/M phase at 50 microM.
      For both, rapid proliferating cells and stressed apoptotic cells, complete growth
      inhibition occurred at 85 microM, with cells being arrested in the G(2)/M phase
      and dying mainly through necrosis. Cells in the bioreactor system appeared to be
      more sensitive towards linoleic acid than cells grown in multi-well plates.
      (IC(50) = 300 microM; IC(100) = 400 microM). Altogether the results of the
      present study reveal that the biostat experiments allow detailed analysis of the
      effect of a bioactive ingredient on cell physiology and behavior.

PMID- 16894631
TI  - Retrospective optimization of time-dependent fermentation control strategies
      using time-independent historical data.
AB  - We have previously shown the usefulness of historical data for fermentation
      process optimization. The methodology developed includes identification of
      important process inputs, training of an artificial neural network (ANN) process
      model, and ultimately use of the ANN model with a genetic algorithm to find the
      optimal values of each critical process input. However, this approach ignores the
      time-dependent nature of the system, and therefore, does not fully utilize the
      available information within a database. In this work, we propose a method for
      incorporating time-dependent optimization into our previously developed three
      step optimization routine. This is achieved by an additional step that uses a
      fermentation model (consisting of coupled ordinary differential equations (ODE))
      to interpret important time-course features of the collected data through
      adjustments in model parameters. Important process variables not explicitly
      included in the model were then identified for each model parameter using
      automatic relevance determination (ARD) with Gaussian process (GP) models. The
      developed GP models were then combined with the fermentation model to form a
      hybrid neural network model that predicted the time-course activity of the cell
      and protein concentrations of novel fermentation conditions. A hybrid-genetic
      algorithm was then used in conjunction with the hybrid model to suggest optimal
      time-dependent control strategies. The presented method was implemented upon an
      E. coli fermentation database generated in our laboratory. Optimization of two
      different criteria (final protein yield and a simplified economic criteria) was
      attempted. While the overall protein yield was not increased using this
      methodology, we were successful in increasing a simplified economic criterion by
      15% compared to what had been previously observed. These process conditions
      included using 35% less arabinose (the inducer) and 33% less typtone in the media
      and reducing the time required to reach the maximum protein concentration by 10%
      while producing approximately the same level of protein as the previous optimum.

PMID- 16894632
TI  - Poly(lactic-co-glycolic acid) hollow fibre membranes for use as a tissue
      engineering scaffold.
AB  - Mass transfer limitations of scaffolds are currently hindering the development of
      3-dimensional, clinically viable, tissue engineered constructs. We have developed
      a poly(lactide-co-glycolide) (PLGA) hollow fibre membrane scaffold that will
      provide support for cell culture, allow psuedovascularisation in vitro and
      provide channels for angiogenesis in vivo. We produced P(DL)LGA flat sheet
      membranes using 1, 4-dioxane and 1-methyl-2-pyrrolidinone (NMP) as solvents and
      water as the nonsolvent, and hollow fibre membranes, using NMP and water, by
      dry/wet- and wet-spinning. The resulting fibres had an outer diameter of 700
      micro m and an inner diameter of 250 micro m with 0.2-1.0 micro m pores on the
      culture surface. It was shown that varying the air gap and temperature when
      spinning changed the morphology of the fibres. The introduction of a 50 mm air
      gap caused a dense skin of 5 micro m thick to form, compared to a skin of 0.5
      micro m thick without an air gap. Spinning at 40 degrees C produced fibres with a
      more open central section in the wall that contained more, larger macrovoids
      compared to fibres spun at 20 degrees C. Culture of the immortalised osteogenic
      cell line 560pZIPv.neo (pZIP) was carried out on the P(DL)LGA flat sheets in
      static culture and in a P(DL)LGA hollow fibre bioreactor under counter-current
      flow conditions. Attachment and proliferation was statistically similar to tissue
      culture polystyrene on the flat sheets and was also successful in the hollow
      fibre bioreactor. The P(DL)LGA hollow fibres are a promising scaffold to address
      the size limitations currently seen in tissue engineered constructs.

PMID- 16894634
TI  - Salt stress effects on the central and carnitine metabolisms of Escherichia coli.
AB  - The aim was to understand how interaction of the central carbon and the secondary
      carnitine metabolisms is affected under salt stress and its effect on the
      production of L-carnitine by Escherichia coli. The biotransformation of
      crotonobetaine into L-carnitine by resting cells of E. coli O44 K74 was improved
      by salt stress, a yield of nearly twofold that for the control being obtained
      with 0.5 M NaCl. Crotonobetaine and the L-carnitine formed acted as an
      osmoprotectant during cell growth and biotransformation in the presence of NaCl.
      The enzyme activities involved in the biotransformation process (crotonobetaine
      hydration reaction and crotonobetaine reduction reaction), in the synthesis of
      acetyl-CoA/acetate (pyruvate dehydrogenase, acetyl-CoA synthetase [ACS] and
      ATP/acetate phosphotransferase) and in the distribution of metabolites for the
      tricarboxylic acid cycle (isocitrate dehydrogenase [ICDH]) and glyoxylate shunt
      (isocitrate lyase [ICL]) were followed in batch with resting cells both in the
      presence and absence of NaCl and in perturbation experiments performed on growing
      cells in a high density cell recycle membrane reactor. Further, the levels of
      carnitine, crotonobetaine, gamma-butyrobetaine and ATP and the NADH/NAD(+) ratio
      were measured in order to know how the metabolic state was modified and coenzyme
      pools redistributed as a result of NaCl's effect on the energy content of the
      cell. The results provided the first experimental evidence of the important role
      played by salt stress during resting and growing cell biotransformation (0.5 M
      NaCl increased the L-carnitine production in nearly 85%), and the need for high
      levels of ATP to maintain metabolite transport and biotransformation. Moreover,
      the main metabolic pathways and carbon flow operating during cell
      biotransformation was that controlled by the ICDH/ICL ratio, which decreased from
      8.0 to 2.5, and the phosphotransferase/ACS ratio, which increased from 2.1 to
      5.2, after a NaCl pulse fivefold the steady-state level. Resting E. coli cells
      were seen to be made up of heterogeneous populations consisting of several types
      of subpopulation (intact, depolarized, and permeabilized cells) differing in
      viability and metabolic activity as biotransformation run-time and the NaCl
      concentration increased. The results are discussed in relation with the general
      stress response of E. coli, which alters the NADH/NAD(+) ratio, ATP content, and
      central carbon enzyme activities.

PMID- 16894633
TI  - Thermally induced gelable polymer networks for living cell encapsulation.
AB  - We report the encapsulation of MIN6 cells, a pancreatic beta-cell line, using
      thermally induced gelable materials. This strategy uses aqueous solvent and mild
      temperatures during encapsulation, thereby minimizing adverse effects on cell
      function and viability. Using a 2:1 mixture of PNIPAAm-PEG-PNIPAAm tri-block
      copolymer and PNIPAAm homopolymer that exhibit reversible sol-to-gel transition
      at approximately 30 degrees C, gels were formed that exhibit mechanical
      integrity, and are stable in H(2)O, PBS and complete DMEM with negligible mass
      loss at 37 degrees C for 60 days. MTT assays showed undetectable cytotoxicity of
      the polymers towards MIN6 cells. A simple microencapsulation process was
      developed using vertical co-extrusion and a 37 degrees C capsule collection bath
      containing a paraffin layer above DMEM. Spherical capsules with diameters ranging
      from 500 to 900 microm were formed. SEM images of freeze-dried capsules with PBS
      as the core solution showed homogenous gel capsule membranes. Confocal microscopy
      revealed that the encapsulated cells tended to form small aggregates over 5 days,
      and staining for live and dead cells showed high viability post-encapsulation. A
      static glucose challenge with day-5 cultured microencapsulated cells exhibited
      glucose-dependent insulin secretion comparable to controls of free MIN6 cells
      grown in monolayers. These results demonstrate the potential use of these thermo
      responsive polymers as cell encapsulation membranes.

PMID- 16894635
TI  - Successful transfection of hepatoma cells after encapsulation of plasmid DNA into
      negatively charged liposomes.
AB  - The application of conventional cationic liposomes/DNA complexes in gene transfer
      was hampered due to their large size, instability, and limited transfection site
      in vivo. In this report, we described a dialysis-based method and produced small,
      stable, and negatively charged DNA-containing liposomes composed of low content
      of cationic lipid and high content of fusogenic lipid. The liposomes were
      relatively spherical with a condensed core inside, and exhibited small size with
      narrow particle size distribution. The encapsulation efficiency of the liposomes
      was 42.53 +/- 2.29%. They were stable and showed enough protective ability to
      plasmid DNA from degradation after incubation with different amounts of DNase.
      Twenty-fold higher transfection efficiency for the liposomes was achieved when
      compared with that of naked plasmid DNA and no toxicities to hepatocellular
      carcinoma cells were observed. Our results indicate that the negatively charged
      DNA-containing liposomes can facilitate gene transfer in cultured cells, and may
      alleviate the drawbacks of the conventional cationic liposomes/DNA complexes for
      gene delivery in vivo.

PMID- 16894636
TI  - Study of the near-neutral pH-sensitivity of chitosan/gelatin hydrogels by
      turbidimetry and microcantilever deflection.
AB  - The fundamental properties and pH-sensitivity of chitosan/gelating hydrogels were
      investigated using spectroscopic and microelectro mechanical (MEMS) measurement
      approaches. Turbidimetric titration revealed that there were electrostatic
      attractive interactions between tripolyphosphate (TPP), chitosan, and gelatin in
      the acidic pH range, depending on their degree of ionization. The pH-sensitive
      swelling behavior of the hydrogels was investigated by monitoring the deflection
      of hydrogel-coated microcantilevers, which exhibited a sensitive and repeatable
      response to solution pH. The deflection of the microcantilever increased as the
      pH decreased, and the response speed of the system exhibited a nearly linear
      relationship with pH. The effects of the pH and concentration of TPP solution, as
      well as the ratio of chitosan to gelatin in gel precursor solutions, on the pH
      sensitivity of the hydrogels were also investigated. It was found that the
      swelling of the hydrogel is mainly a result of chain relaxation of chitosan-TPP
      complexes caused by protonation of free amino groups in chitosan, which depends
      on the crosslinking density set during the formation of the network. An increase
      in initial crosslink density induced a decrease in swelling and pH sensitivity.
      It can be concluded from this study that pH-sensitive chitosan gel properties can
      be tuned by preparatory conditions and inclusion of gelatin. Furthermore,
      microcantilevers can be used as a platform for gaining increased understanding of
      environmentally sensitive polymers.

PMID- 16894637
TI  - Effect of inhibition treatment, type of inocula, and incubation temperature on
      batch H2 production from organic solid waste.
AB  - Two types of induction treatments (heat-shock pretreatment, HSP, and acetylene,
      Ac), inocula (meso and thermophilic) and incubation temperatures (37 and 55
      degrees C) were tested according to a full factorial design 2(3) with the aim of
      assessing their effects on cumulative H(2) production (P(H), mmol H(2)/mini
      reactor), initial H(2) production rate (R(i,H), micromol H(2)/(g VS(i) x h)), lag
      time (T(lag), h), and metabolites distribution when fermenting organic solid
      waste with an undefined anerobic consortia in batch mini-reactors. Type of
      inocula did not have a significant effect on P(H), T(lag), and R(i,H) except for
      organic acids production: mini-reactors seeded with thermophilic inocula had the
      highest organic acid production. Concerning the induction treatment, it was found
      that on the average Ac only affected in a positive way the P(H) and T(lag). Thus,
      P(H) in Ac-inhibited units (6.97) was 20% larger than those in HSP-inhibited
      units (5.77). Also, Ac favored a shorter T(lag) for P(H) in comparison with HSP
      (180 vs. 366). Additionally, a positive correlation was found between H(2) and
      organic acid production. In contrast, solvent concentration in heat-shocked mini
      reactors were slightly higher than in reactors spiked with Ac. Regarding the
      incubation temperature, on the average mesophilic temperature affected in a
      positive and very significant way P(H) (10.07 vs. 2.67) and R(i,H) (2.43 vs.
      0.76) with minimum T(lag) (87 vs. 459). The positive correlation between H(2) and
      organic acids production was found again. Yet, incubation temperature did not
      seem to affect solvent production. A strong interaction was observed between
      induction treatment and incubation temperature. Thus, Ac-inhibited units showed
      higher values of P(H) and R(i,H) than that HSP-inhibited units only under
      thermophilic incubation. Contrary to this, HSP-inhibited units showed the highest
      values of P(H) and R(i,H) only under mesophilic conditions. Therefore, the
      superiority of an induction treatment seems to strongly depend on the incubation
      temperature.

PMID- 16894638
TI  - Targeting early apoptotic genes in batch and fed-batch CHO cell cultures.
AB  - Based on the transcriptional profiling of CHO cell culture using microarray, four
      key early apoptosis signaling genes, Fadd, Faim, Alg-2, and Requiem, were
      identified and CHO GT (Gene Targeted) cell lines were developed by targeting
      these four genes. Two were CHO GT(O) cell lines overexpressing anti-apoptotic
      genes, Faim and Fadd DN and two were CHO GT(KD) cell lines involving knockdown of
      Alg-2 and Requiem which are pro-apoptotic genes using small interfering RNA
      (siRNA) technology. Comparisons of these CHO GT cell lines with the parental cell
      line in batch culture (BC) and fed-batch culture (FBC) were performed. Compared
      to parental cells, the CHO GT cell lines showed apoptosis resistance as they
      significantly delayed and/or suppressed initiator caspase-8 and -9 and
      executioner caspase-3 activities during culture. FBC of CHO GT cell lines reached
      significantly higher maximum viable cell densities (up to 9 x 10(6) cells/mL)
      compared with the parental cell line (5 x 10(6) cells/mL). The recombinant
      interferon gamma (IFN-gamma) yields were increased by up to 2.5-fold.
      Furthermore, it was observed that the IFN-gamma was more highly sialylated.

PMID- 16894639
TI  - Endogenous functional CBV contrast revealed by diffusion weighting.
AB  - Functional MRI (fMRI) based on the blood oxygenation level dependent (BOLD)
      contrast often suffers from a lack of specificity because of the vascular spread
      of oxygenation changes. It is suggested from the optical imaging and animal fMRI
      literature that cerebral blood volume (CBV) changes are more closely tied to the
      smaller vessels. As such, fMRI contrast based on CBV changes will have improved
      spatial specificity to the neuronal activities as they are immediately adjacent
      to the smaller vessels. In this paper, an endogenous contrast mechanism based on
      a diffusion weighting strategy that could detect functional CBV changes is
      presented. Initially, a theoretical framework is presented to model the
      functional signal changes as a function of CBV under diffusion weighting, which
      predicts peak CBV sensitivity at various vessel-tissue mixtures. It was found
      that a b factor over 1500 s/mm(2) would be necessary to achieve dominant CBV
      contrast. Further, two sets of experimental results are also presented. In the
      first experiment, diffusion weighting at a set of b factors ranging from 300 to
      600 s/mm(2) was used. The results indicated that while the positive activation
      (predominantly BOLD signal) continued to reduce in magnitude and spatial extent,
      the negative activation (predominantly CBV signal) remained virtually constant
      with increasing b factors. The second experiment used a b factor of 1600 s/mm(2)
      and showed extensive negative activation in the visual cortex and greatly reduced
      positive activations compared with images with no diffusion weighting. The time
      course of negative activation showed a faster time to peak and return to baseline
      than the positive BOLD activity, consistent with the small vessel origin of the
      signal changes. These results suggest that appropriate diffusion weighting could
      be used to measure activation related CBV changes.

PMID- 16894640
TI  - Transrectal ultrasound-guided biopsy of prostate voxels identified as suspicious
      of malignancy on three-dimensional (1)H MR spectroscopic imaging in patients with
      abnormal digital rectal examination or raised prostate specific antigen level of
      4-10 ng/ml.
AB  - Results of the evaluation of transrectal ultrasound (TRUS) guided needle biopsy
      of voxels identified as suspicious of malignancy on magnetic resonance
      spectroscopic imaging (MRSI) in a large cohort of men (n = 83) with abnormal
      digital rectal examination (DRE) [prostate specific antigen (PSA) 0-4 ng/ml] or
      PSA less than 10 ng/ml, are reported. Three-dimensional (1)H MRSI was carried out
      at 1.5 T using a pelvic-phased array coil in combination with an endorectal
      surface coil. Voxels were classified as suspicious of malignancy based on
      Cit/(Cho + Cr) metabolite ratio. TRUS-guided biopsy of suspicious voxels was
      performed using the z- and x-coordinates obtained from MR images and two to three
      cores were taken from the suspected site. A systematic sextant biopsy was also
      carried out. MRSI showed voxels suspicious of malignancy in 44 patients while
      biopsy revealed cancer in 11 patients (25%). Patients who were negative for
      malignancy on MRSI were also negative on biopsy. An overall sensitivity of 100%,
      specificity of 54%, negative predictive value of 100% and accuracy of 60% were
      obtained. The site of biopsy was confirmed (n = 20) as a hypo-intense area on
      repeat MRI while repeat MRSI revealed high choline and low citrate. The overall
      success rate of MRI-directed TRUS-guided biopsy of 25% was higher compared with a
      9% success rate achieved without MR guidance in another group of 120 patients.
      Our results indicate that TRUS-guided biopsy of suspicious area identified as
      malignant from MRSI can be performed using the coordinates of the voxel derived
      from MR images. This increases the detection rate of prostate cancer in men with
      PSA level <10 ng/ml or abnormal DRE and also demonstrates the potential of MR in
      routine clinical practice.

PMID- 16894641
TI  - Job loss and reemployment after a cancer diagnosis in Koreans - a prospective
      cohort study.
AB  - Patients undergoing treatment for cancer have reported a variety of work-related
      problems. The aim of this study was to investigate the impact of a cancer
      diagnosis on employment status, and to identify relevant associated factors. This
      prospective cohort study was conducted at the National Cancer Center in Korea.
      Male patients newly diagnosed with stomach, liver, or colorectal cancers were
      recruited. Patients were interviewed and asked to complete an employment
      questionnaire every 3 months for 24 months. Clinical, sociodemographic and work
      related factors were assessed. There were 305 male patients who had a primary
      diagnosis of cancer and underwent appropriate treatment. Of the 305 male patients
      who were employed at the time of diagnosis, 53% lost their job, and of these 23%
      later reemployed. In a multivariate Cox regression analysis, job loss was
      significantly associated with years of education, job characteristics and disease
      stage. Reemployment was significantly associated with disease stage and cancer
      site. Change of employment was common among cancer patients in Korea. With an
      understanding of the factors involved, it should be possible to reduce
      unnecessary work cessation, and increase the rate of employment of cancer
      survivors.

PMID- 16894642
TI  - Repellency of Cinnamomum cassia bark compounds and cream containing cassia oil to
      Aedes aegypti (Diptera: Culicidae) under laboratory and indoor conditions.
AB  - Patch and skin bioassays were used in laboratory and indoor tests to evaluate the
      repellency of (E)-cinnamaldehyde, identified in Cinnamomum cassia Blume bark and
      essential oil, and a cream containing 5% (w/w) cassia oil against Aedes aegypti
      (L.) females. Results were compared with those of a known C. cassia compound
      cinnamyl alcohol, N,N-diethyl-m-toluamide (DEET) and two commercial repellents:
      MeiMei cream containing citronella and geranium oils and Repellan S aerosol
      containing 19% DEET. In patch bioassay tests with A. aegypti females, (E)
      cinnamaldehyde at 0.153 mg cm(-2) and DEET at 0.051 mg cm(-2) provided 93 and 89%
      protection at 40 min after exposure. In skin bioassay tests, (E)-cinnamaldehyde
      at 0.051 mg cm(-2) and DEET at 0.025 mg cm(-2) provided 87 and 95% protection at
      30 min after application. (E)-Cinnamaldehyde was significantly more effective
      than cinnamyl alcohol in both bioassays. In indoor tests with four human
      volunteers, 5% cassia oil cream provided 94, 83 and 61% protection against A.
      aegypti females exposed for 30, 50 and 70 min after application respectively.
      Cassia oil cream was a slightly less effective repellent than MeiMei cream.
      Repellan S aerosol provided 91% repellency at 120 min after application. Products
      containing cassia oil merit further study as potential repellents for the
      protection of humans and domestic animals from blood-feeding vectors and the
      diseases they transmit.

PMID- 16894643
TI  - Proton and sodium MRI assessment of emerging tumor chemotherapeutic resistance.
AB  - The ultimate goal of any cancer therapy is to target the elimination of
      neoplastic cells. Although newer therapeutic strategies are in constant
      development, therapeutic assessment has been hampered by the inability to assess,
      rapidly and quantitatively, efficacy in vivo. Diffusion imaging and, more
      recently, sodium MRI have demonstrated their distinct abilities to detect therapy
      induced alterations in tumor cellularity, which has been demonstrated to be
      indicative of therapeutic efficacy. More importantly, both imaging modalities
      detect tumor response much earlier than traditional methodologies that rely on
      macroscopic volumetric changes. In this study, the correlation between tumor
      sodium and diffusion was further tested to demonstrate the sensitivity of sodium
      imaging to gauge tumor response to therapy by using a 9L rat gliosarcoma treated
      with varying doses of BCNU [1,3-bis(2-chloroethyl)-1-nitrosourea]. This
      orthotopic model has been demonstrated to display variability in response to BCNU
      therapy where initial insult has been shown to lead to drug-resistance. In brief,
      a single 26.6 mg/kg BCNU dose yielded dramatic responses in both diffusion and
      sodium MRI. However, a second equivalent BCNU dose yielded a much smaller change
      in diffusion and sodium, suggesting a drop in tumor sensitivity to BCNU. The MRI
      responses of animals treated with 13.3 mg/kg BCNU were much lower and similar
      responses were observed after the initial and secondary applications of BCNU.
      Furthermore, these results were further validated using volumetric measurements
      of the tumor and also ex vivo determination of tumor sensitivity to BCNU.
      Overall, these experiments demonstrate the sensitivity and applicability of
      sodium and diffusion MRI as tools for dynamic assessment of tumor response to
      therapy.

PMID- 16894644
TI  - Comparative cytochrome P450 -1A1, -2A6, -2B6, -2C, -2D6, -2E1, -3A5 and -4B1
      expressions in human larynx tissue analysed at mRNA level.
AB  - The metabolic activation of numerous exogenous and endogenous chemicals is
      catalysed by cytochrome P450 enzymes (CYPs). The aim of this study was to analyse
      the expression of the individual forms of CYP at the mRNA level in human larynx
      and quantitatively to compare their expressions in human liver, the main organ of
      CYP expression. Individual forms of CYP mRNAs were detected by reverse
      transcriptase-polymerase chain reaction (RT-PCR) using specific primers for the
      CYPs -1A1, -1A2, -2A6, -2B6, -2C, -2D6, -2E1, -3A3/4, -3A5, -3A7 and -4B1. An RNA
      competitor of known copy number, covering the primer sequences necessary to
      amplify the entire object CYPs within a single molecule, was used as reference.
      This study reports a consistent detection of mRNAs for the CYPs -1A1, -2A6, -2B6,
      -2C, -2D6, -2E1, -3A5 and -4B1 in the human larynx tissue. The data indicate that
      the human larynx highly resembles the lung tissue in CYP content, as a comparable
      subset of CYP mRNAs was detected in the larynx previously reported for human lung
      with the exception of CYP1A2. The results are discussed in quantitative ratios of
      the detected CYP mRNAs in relation to the hepatic CYP expression.

PMID- 16894645
TI  - Pharmacokinetics of omeprazole in rats with water deprivation for 72 hours.
AB  - Dehydration can occur by excessive sweating, polyuria, severe diarrhea and
      hyperthermia. Previous studies reported that the expressions of CYP1A1/2 and
      3A1(23)/2 were not changed in male Sprague-Dawley rats with 72 h water
      deprivation (dehydrated rats), and that the metabolism of omeprazole is mainly
      catalysed via CYP1A1/2, 2D1 and 3A23/2 in rats. Hence, it could be expected that
      the hepatic metabolism of omeprazole would not be changed considerably in
      dehydrated rats, if the contribution of CYP2D1 to the metabolism of omeprazole in
      dehydrated rats is not considerable. Therefore, the pharmacokinetics of
      omeprazole were compared after intravenous (20 mg/kg) and oral (40 mg/kg)
      administration in control rats and in dehydrated rats. After intravenous
      administration, the time-averaged nonrenal clearance (Cl(nr)) values of
      omeprazole were comparable between the two groups of rats. This could be
      supported by comparable in vitro intrinsic clearance (Cl(int)) values for the
      disappearance of omeprazole in rat hepatic microsomes and the comparable free
      (unbound to plasma proteins) fractions of omeprazole in plasma in the two groups
      of rats. After oral administration, the AUC values of omeprazole were also
      comparable in the two groups of rats. The above data suggest that the dehydration
      state did not affect considerably the pharmacokinetics of omeprazole in rats.

PMID- 16894646
TI  - Cardiovascular variability is/is not an index of autonomic control of
      circulation.

PMID- 16894647
TI  - Cardiovascular variability is/is not an index of autonomic control of
      circulation.

PMID- 16894648
TI  - Cardiovascular variability is/is not an index of autonomic control of
      circulation.

PMID- 16894649
TI  - Cardiovascular variability is/is not an index of autonomic control of
      circulation.

PMID- 16894650
TI  - Cardiovascular variability is/is not an index of autonomic control of
      circulation.

PMID- 16894651
TI  - Russia's blossoming civil society holds the key to HIV.

PMID- 16894652
TI  - Optimizing your optical tweezers.
AB  - A new measurement theory for dual-trap optical tweezers shows researchers for the
      first time how to easily optimize their experiments to limit noise from Brownian
      movement.

PMID- 16894654
TI  - Making a move.

PMID- 16894655
TI  - Vulnerability of practitioners to litigation.

PMID- 16894653
TI  - Primary treatment of a blister-like aneurysm with an encircling clip graft:
      technical case report.
AB  - OBJECTIVE: Blister-like aneurysms at nonbranching sites in the supraclinoid
      portion of the internal carotid artery are a rare but important cause of
      subarachnoid hemorrhage. We report a case of subarachnoid hemorrhage caused by a
      ruptured blister-type aneurysm, review the pertinent literature, and hope to
      remind readers of the wisdom of the use of an encircling clip as the primary
      treatment of these challenging lesions. CLINICAL PRESENTATION: A 41-year-old
      woman presented with sudden onset of headache. An admission computed tomographic
      (CT) scan revealed thick and diffuse subarachnoid hemorrhage involving primarily
      the carotid cistern and the proximal left sylvian fissure. A cerebral angiogram
      was initially interpreted as absent for aneurysm, but a follow-up angiogram
      performed 1 week later confirmed an enlarging aneurysm. INTERVENTION: A
      craniotomy with placement of an encircling clip graft around a blister-like
      aneurysm was performed. CONCLUSION: Although Sundt advocated the encircling clip
      graft for the blister-type aneurysm almost 40 years ago, use of an encircling
      clip graft in the treatment of blister-like aneurysms of the supraclinoid portion
      of the internal carotid artery seems to be reserved as a secondary or "rescue"
      measure in current practice. Neurosurgeons must familiarize themselves with this
      distinct entity (the blister-type aneurysm), recognize the possible risks
      associated with parallel clipping, and consider the use of an encircling clip
      graft as the primary treatment.

PMID- 16894656
TI  - Ombudsman observations: A belated New Year's resolution--don't help your
      patients!

PMID- 16894657
TI  - Ragweed pollen travels long distance.

PMID- 16894658
TI  - Re: Craigie RJ, Duncan JL, Youngson GG. Children's surgery performed by adult
      general surgeons in Scotland: the present and future. Surgeon 2005; 3(6): 391-94.

PMID- 16894659
TI  - Re: Golash V, Cutress R. Laparoscopic cytogastrostomy for a giant pseudocyst of
      pancreas. Surgeon 2004; 3(1): 37-41.

PMID- 16894661
TI  - The frozen section comes of age.

PMID- 16894660
TI  - Trustee workbook 3. Strategic planning: maximizing the board's impact.

PMID- 16894662
TI  - Deactivation of an implantable cardioverter defibrillator in a dying patient.

PMID- 16894663
TI  - MI: home health nurse injured in fall on ice: should she have followed her path
      of entry?

PMID- 16894664
TI  - And the winner is...

PMID- 16894665
TI  - [The 38th annual meeting of the Japan Atherosclerosis Society. Tokyo, Japan. July
      13-14, 2006. Program and Abstracts].

PMID- 16894666
TI  - Abstracts of the 20th Meeting of the European Intestinal Transport Group,
      September 24-27, 2005, Oleron, France.

PMID- 16894667
TI  - Proceedings of the meeting on geriatric endocrinology devoted to the issue of
      aging male, Parma, Italy, December 6-7, 2004.

PMID- 16894668
TI  - n-3 Fatty Acids: Recommendations for Therapeutics and Prevention. Proceedings of
      a symposium, New York, New York, USA, May 21, 2005.

PMID- 16894669
TI  - Degenerative spine disease.

PMID- 16894671
TI  - Bibliography. Current world literature. Facial plastic surgery.

PMID- 16894670
TI  - Novel approaches in the outpatient care of patients with chronic inflammatory
      bowel disease.
AB  - Treatment strategies for Crohn's disease are targeted toward lifelong management.
      Optimization of outpatient care is mandatory, because of many clinics facing
      capacity issues, and, along with routine follow-up of patients with inflammatory
      bowel disease, is putting increasing pressure on outpatient clinics. Recent
      studies demonstrate clearly that alternative management strategies are feasible
      and effective with a high rate of patient satisfaction. It is recommended that
      future research evaluates the way in which medical care is provided and explores
      the long-term effects of novel management strategies in IBD. This approach can
      then be extrapolated to other chronic conditions.

PMID- 16894672
TI  - Bibliography. Current world literature. Infections of the immunocompromised host.

PMID- 16894673
TI  - Onychomycosis: a prospective survey of prevalence and etiology in Madrid.

PMID- 16894674
TI  - It cuts both ways.

PMID- 16894675
TI  - Dentistry--an honourable profession?

PMID- 16894678
TI  - [The South African Dental Association and dentists in the field].

PMID- 16894680
TI  - The relation between toothpaste usage and fluorosis: a cause for concern?
AB  - Fluoride-containing toothpaste is by far the most widespread source of fluoride
      in the world and after fluoridated water the most cost-effective at reducing
      dental caries. Of the seven current issues in the development of fluoride
      containing toothpaste described by Holt & Murray (1997), five are either directly
      or indirectly related to the risk of developing fluorosis, a phenomenon which is
      on the increase in the industrialised world. The purpose of this study was to
      evaluate fluoride-containing toothpaste available to the South African public
      regarding the issues described by Holt & Murray (1997) and to relate the results
      to the possible development of fluorosis. The amount of fluoride ingested from
      toothpaste was calculated using the total fluoride concentration present in
      toothpaste, quantity of toothpaste used per brushing, mean percentage of
      toothpaste ingested and the 90th percentile of body weight. Results indicate that
      the "threshold" level of fluoride intake of 0.05 to 0.07 mg F/kg body weight/day
      beyond which dental fluorosis might occur (Burt, 1992), is exceeded when a ribbon
      of toothpaste was placed on a child's toothbrush at ages 2-3 years. 'Threshold'
      levels were ingested when placing a ribbon of toothpaste on the brush at ages 4
      and 5 for all toothpaste as well as for a children's formulation containing 1000
      microg F/g. Of all pastes studied, 41.9% of the packaging has information for the
      prevention of swallowing of paste and/or the supervision of children by adults
      when brushing. The dental profession, manufacturers of toothpaste and government
      all have a role to play in the prevention of fluorosis in the toothbrushing
      population of South Africa.

PMID- 16894679
TI  - Laboratory analysis of fluoride containing toothpaste available in South Africa.
AB  - Since the introduction of fluoridated toothpaste more than 30 years ago, it has
      become by far the most widespread source of fluoride in the world and after
      fluoridated water the most effective at reducing dental caries. Both the total
      soluble and the soluble ionic fluoride present in toothpaste are important in
      determining the effectiveness of the paste as it is important in remineralising
      demineralised lesions, a characteristic of fluoride which has proven to be the
      most important in preventing dental caries. The purpose of this study was to
      evaluate toothpaste currently available to the South African public regarding
      total soluble and soluble ionic fluoride. A variation of the method used by
      Grobler et al. (1983) and Du Preez et al. (1993) in previous studies conducted in
      South Africa was used in preparing the samples for fluoride analysis.
      Measurements of fluoride concentrations were done using an ionselective
      electrode. For all toothpaste studied (n=62), large variations occurred for the
      soluble ionic fluoride (mean = 318.44 microg F/g toothpaste; median = 139.69;
      standard deviation = 398.77). Correspondingly a mean total soluble fluoride of
      848.84 microg F/g toothpaste was found (standard deviation = 189.35; median =
      857.38). From this study it can be concluded that fluoride concentrations in
      toothpaste available to the South African public are in line with those found in
      the two previous South African studies. In the absence of artificially
      fluoridated water, toothpaste remains the most cost-effective strategy in the
      prevention of dental caries in South Africa.

PMID- 16894681
TI  - Prosthetic restoration following maxillary trauma utilising a fixed removable
      implant-supported prosthesis: a case report.
AB  - Patients with traumatic head injuries may suffer from tooth loss, as well as
      involvement of associated soft tissues and bone. Conventional prostheses are
      often bulky and unretentive. Osseo-integrated implants have made it possible to
      treat these patients with more retentive, aesthetically and functionally improved
      prostheses. This case illustrates the use of a fixed removable implant-supported
      prosthesis for a patient with severe maxillary trauma. A bar connecting the
      implants was individually designed to have parallel sides and vertical channels
      prepared in it. The corresponding removable prosthesis features retentive pins
      which engage the prepared grooves in the bar to provide adequate frictional
      retention and stability for the prosthesis. This treatment modality restored the
      missing teeth, alveolar bone, soft tissues and oral function while at the same
      time facilitating good oral hygiene.

PMID- 16894683
TI  - Why water fluoridation in South Africa?

PMID- 16894682
TI  - Report on the nursing bottle caries campaign launched by the Free State Oral
      Health Services.

PMID- 16894684
TI  - Oral hygienists' education in transition.
AB  - In 1996 the Dental Faculty of the University of the Western Cape introduced a
      modular curriculum for Oral Hygiene students. The aim was to change from a
      subject-based to an outcomes-based programme, which would emphasise the
      competencies of hygienists. The development of this programme has meant ongoing
      evaluation and therefore amendments and revisions have been made throughout the
      course. This curriculum could be re-registered with the South African
      Qualifications Authority (SAQA) which describes competencies for the eight main
      level descriptors. This new approach to teaching allows for a laddered approach
      to training with intermediate exit qualifications. Oral hygienists' would thus
      for the first time have a career path in the oral health profession as it allows
      them to proceed from a Diploma to a Degree and to have the prospect of doing a
      Masters Degree.

PMID- 16894685
TI  - Report of the chairman of the Private Practice Committee: problems encountered
      with medical schemes.

PMID- 16894686
TI  - DentiServe and dental disbursements.

PMID- 16894687
TI  - Capitation is coming.

PMID- 16894689
TI  - A message from the new dental advisor to Medscheme.

PMID- 16894688
TI  - Are we the pawns or kings of the healthcare chessboard?

PMID- 16894690
TI  - Rural dentistry through the eyes of a CSDO.

PMID- 16894691
TI  - [Microleakage of four different amalgam binding systems].
AB  - This-study was undertaken to evaluate and compare microleakage in class V
      cavities in human teeth which were lined with Amalgambond Plus with HPA (Parkell,
      USA), Optibond Solo (Kerr, U.S.A.), Fuji Plus (GC Corporation, Japan) and Prime &
      Bond 2.1 (Dentsply, Switzerland), and then restored with Logic amalgam (SDI
      Australia). The restored teeth were thermocycled in basic fuchsin dye, sectioned,
      and evaluated for dye penetration. The interdiffusion zones were viewed in a
      confocal laser scanning microscope (CLSM). The results showed that no bonding
      system could totally eliminate microleakage. Statistical analysis revealed
      significant differences between Amalgambond Plus with HPA and Prime & Bond 2.1,
      Fuji Plus as well as Optibond Solo, for both the enamel and dentine sides. No
      significant differences were found between Prime & Bond 2.1, Fuji Plus and
      Optibond Solo, for both the enamel and dentine sides. Amalgambond Plus showed
      significantly more leakage at dentine sides while Prime & Bond 2.1 showed
      significantly more leakage at enamel sides. The CLSM revealed hybrid layers of
      different thicknesses, resin penetration into tubules, as well as resin
      incorporation within the spherical particles of the amalgam. Optibond Solo, Fuji
      Plus and Prime & Bond 2.1 can serve to improve the marginal seal of amalgam
      restorations.

PMID- 16894692
TI  - Cost evaluation for the implementation of water fluoridation in Gauteng.
AB  - Regulations to implement water fluoridation in South Africa were promulgated in
      September 2000. Water providers are now compelled to fluoridate public water
      sources. In terms of Regulation 5(c) of the regulations, certain information
      regarding the cost of water fluoridation must be submitted to the Director
      General of Health. The purpose of this survey was to evaluate the cost of water
      fluoridation in Gauteng and to provide a model for similar calculations in other
      provinces. The following criteria were used to evaluate the cost of water
      fluoridation in Gauteng--per capita cost per year, cost-effectiveness analysis
      (CEA) and cost-benefit analysis (CBA). The calculated cost per capita per year
      was R0.73 while CEA showed that R3.95 will be spent to save 1 DMFT. The cost
      benefit ratio based on the scale of benefits cost of a 2 surface plastic
      restoration was 0.04. Evaluation of cost for the implementation of water
      fluoridation in Gauteng was extremely favourable and a model to estimate the per
      capita figure is provided.

PMID- 16894693
TI  - 9th biennial scientific meeting of the International Association for Craniofacial
      Identification 24-29 July 2000, Washington DC.

PMID- 16894694
TI  - Identification by means of the teeth.

PMID- 16894695
TI  - To splint or not to splint, that is the question.

PMID- 16894696
TI  - Biology of the pulp.

PMID- 16894697
TI  - Dental education in Queensland I: the 1-3-1 model.
AB  - Dental education worldwide is under great pressure. This pressure is being driven
      not only by changing patterns of oral disease but also by economic factors both
      inside and outside universities. Technological advances and changing educational
      philosophies across the board also impact significantly on what we do and how we
      do it. This article outlines how the School of Dentistry at The University of
      Queensland is responding to these pressures within the context of local
      political, educational and economic realities. The so-called 1-3-1 model that has
      been adopted involves one year of basic science, three years of applied dental
      science and one year of extramural clinical practice. This model represents a
      partnership with the Queensland Department of Health and will: Involve dental
      education and the Dental School in the provision of health care to the community.
      Place the Dental School in a position to influence the delivery and quality of
      oral health care in the population and to assume some of the responsibility for
      it. Provide a wide range of clinical and community experiences for students prior
      to graduation. Allow the adoption of modern teaching methods such as Problem
      Based Learning (PBL) in Years II-IV with all the additional benefits e.g.
      communication skills. Provide an extended clinical period for the acquisition and
      development of clinical and technical skills prior to graduation. Be cost
      effective both to the university and the health service. Allow for outside input
      without compromising the knowledge and research base. It is recognised that while
      the 1-3-1 model may meet the demands of a large, decentralised state such as
      Queensland, it may not be suitable for all institutions. In this context
      diversity in approach is one of the strengths of dental education, nationally and
      internationally.

PMID- 16894698
TI  - New scope of duties for oral hygienists.

PMID- 16894699
TI  - Headache--the dental connection.

PMID- 16894700
TI  - Something's missing: need fulfillment and self-expansion as predictors of
      susceptibility to infidelity.
AB  - The present authors investigated whether an individual's motivations that are
      related to need fulfillment and self-expansion within a romantic relationship can
      predict self-reported susceptibility to infidelity. A sample of 109 college
      students (50 men, 59 women) who were in dating relationships completed
      questionnaires that assessed 5 types of variables of need fulfillment (i.e.,
      intimacy, companionship, sex, security, and emotional involvement), 3 types of
      self-expansion variables (i.e., self-expansion, inclusion of the other in the
      self, and potential for self-expansion), and susceptibility to infidelity. As the
      present authors predicted, both sets of predictors (need fulfillment and self
      expansion) significantly contributed to the variance in susceptibility to
      infidelity. The present findings indicated the possibility that, when a
      relationship is not able to fulfill needs or provide ample self-expansion for an
      individual, his or her susceptibility to infidelity increases.

PMID- 16894701
TI  - Greek Cypriot attitudes toward Turkish Cypriots and Turkish immigrants.
AB  - The authors examined the attitudes of 106 Greek Cypriots toward Turkish Cypriots
      and Turkish immigrants on Cyprus. The authors examined Greek Cypriot attitudes,
      willingness to cohabit with Turkish Cypriots and Turkish immigrants, and the
      reasons behind their attitudes in terms of their social-identity perceptions,
      victimization experiences, and human-rights concerns. A series of repeated
      measures analyses of variance showed that Greek Cypriots were more willing to
      cohabit with and had less negative attitudes toward Turkish Cypriots than they
      were with and toward Turkish immigrants. Women felt more victimized by Turkish
      Cypriots and Turkish immigrants than did men. Perceived differences in social
      identity predicted unwillingness to cohabit with Turkish Cypriots. Feelings of
      victimization predicted negative attitudes toward Turkish Cypriots. Differences
      in social identity and victimization experiences predicted unwillingness to
      cohabit with Turkish immigrants. Differences in social identity predicted
      negative attitudes toward Turkish immigrants. The authors discussed the findings
      in terms of support for realistic group conflict theories of attitudes and their
      implications for the coexistence of these ethnic groups in Cyprus and of other
      ethnic groups in multicultural societies.

PMID- 16894702
TI  - Differential effects of reciprocity and attitude similarity across long- versus
      short-term mating contexts.
AB  - Participants were 24 male and 32 female undergraduate and graduate students whom
      the authors recruited for an examination of the effects of attitude similarity
      and reciprocity on the degree of attraction toward potential mates. The authors
      examined the effects of these 2 variables on degree of liking in long-term and
      short-term contexts. The authors administered a vignette about a bogus stranger
      to each participant, varying the stranger's attitude similarity with and liking
      of the participant. The authors enclosed the vignette in a folder that described
      the stranger as having either very similar or very different attitudes from the
      participant and that included a passage that notified the participant that the
      stranger either likes or does not like him or her. The dependent variables
      included 4 indexes of the extent to which participants reported liking the bogus
      stranger: a scale that measured short-term mating items, a scale that measured
      long-term mating items, a degree-of-liking scale, and a behavioral-intention
      item. Across these 4 attraction-relevant dependent variables, the authors found
      significant main effects of the reciprocity variable. Also, the authors found a
      significant main effect of attitude similarity on the likability measure. The
      authors found significant main effects of reciprocity in a long-term mating
      context and a short-term mating context.

PMID- 16894703
TI  - Beyond politics: authoritarianism and the pursuit of leisure.
AB  - Psychologists know a lot about the political and ideological correlates of people
      scoring high on authoritarianism. However, psychologists have less knowledge
      about such people's everyday pursuits. In the present study, the authors examined
      authoritarian interest in film, live events, music, and reading. A predictable
      pattern of correlates emerged. For example, authoritarians enjoyed activities in
      which physical conflict was prominent, whereas authoritarians tended not to like
      entertainment that offered introspection. In general, the present results were
      consistent across 2 samples (N = 120, N = 90). Although men and women had
      significantly different preferences on over 0.5 of the leisure pursuits (e.g.,
      men enjoyed action films more than did women), there were no significant gender
      differences in the magnitudes of correlates with authoritarianism. In general,
      leisure interests appeared to be partly manifestations or expressions of
      authoritarian tendencies.

PMID- 16894704
TI  - The effects of feedback self-consistency, therapist status, and attitude toward
      therapy on reaction to personality feedback.
AB  - Individuals' reactions to interpersonal feedback may depend on characteristics of
      the feedback and the feedback source. The present authors examined the effects of
      experimentally manipulated personality feedback that they--in the guise of
      therapists--e-mailed to participants on the degree of their acceptance of the
      feedback. Consistent with Self-Verification Theory (W. B. Swann Jr., 1987),
      participants accepted feedback that was consistent with their self-views more
      readily than they did feedback that was inconsistent with their self-views.
      Furthermore, the authors found main effects for therapist's status and
      participant's attitude toward therapy. Significant interactions showed effects in
      which high-status therapists and positive client attitudes increased acceptance
      of self-inconsistent feedback, effects that were only partially mediated by
      clients' perceptions of therapist competence. The present results indicate the
      possibility that participants may be susceptible to self-concept change or to
      self-fulfilling prophecy effects in therapy when they have a positive attitude
      toward therapy or are working with a high-status therapist.

PMID- 16894705
TI  - Does type of team matter? An investigation of the relationships between job
      characteristics and outcomes within a team-based environment.
AB  - The authors examined the relationship between team type (consultative or
      substantive); job characteristics; and the outcome variables of job satisfaction,
      satisfaction with team processes and activities, and team commitment. The present
      results supported the hypothesis that job characteristics mediate the
      relationship between team type and team commitment and partially mediate the
      relationship between team type and job satisfaction and satisfaction with team
      processes and activities. However, contrary to the hypothesis, consultative team
      members perceived the content of their jobs to be more enriched and reported
      higher levels of satisfaction and commitment than did substantive team members.

PMID- 16894706
TI  - Dispositional forgiveness and adult attachment styles.

PMID- 16894708
TI  - A new beginning for South African dentistry.

PMID- 16894710
TI  - The ugly side of capitalism?

PMID- 16894711
TI  - Shear bond strength of one-bottle dentine bonding systems.
AB  - The purpose of this in vitro study was to determine the shear bond strength (SBS)
      of composite resin to human, buccal dentine, using four one-bottle dentine
      bonding systems. Eighty recently extracted human molar teeth were embedded in
      metal rings by means of self-curing acrylic resin. The projecting buccal surfaces
      were ground wet on 600 grit silicone carbide paper in order to expose superficial
      dentine. The teeth were randomly divided into four groups (N=20): 1=Prime&tBond
      2.1 (PB, Dentsply); 2=Scotchbond 1 (SB, 3M); 3=Optibond Solo (OS, Kerr) and
      4=Syntac Single Component (SY, Vivadent). The dentine surfaces were etched,
      treated with one of the four dentine bonding systems, and cylinders of matching
      composites were then bonded to the surfaces by means of a silicone rubber split
      mould. All specimens were stored for 24 hours under water at 37 degrees C. The
      bonds were then stressed to failure with an Instron testing machine, operating at
      a crosshead speed of 0.5 mm/min. The data were statistically analysed (Kruskall
      Wallis). The mean SBS (MPa) were: PB = 12.5 +/- 2.0; SB = 16.2 +/- 1.9; OS = 17.4
      +/- 3.1 and SY= 8.1 +/- 1.9. There was a statistically significant difference (P
      = 0.0001) between the mean of SY and the other 3 groups, and also between PB and
      the other groups. There was no statistically significant difference (P = 0.244)
      between the SBS of OS and SB. SY demonstrated the lowest SBS.

PMID- 16894712
TI  - How does zinc oxide-eugenol compare to ferric sulphate as a pulpotomy material?
AB  - This study compared the clinical and radiographic responses after 3 months to a
      sterile compression technique with zinc oxide-eugenol or 15.5% ferric sulphate in
      145 pulpotomised primary teeth in 30 children. In both groups of teeth the
      success rate was 100%. These short-term results suggest that either technique may
      be used.

PMID- 16894714
TI  - Dental education in Queensland: II. Principles of curriculum design.
AB  - A modern dental curriculum must produce graduates who are competent to practise
      in a variety of settings immediately upon graduation; cognisant of community
      needs and the social milieu in which they serve their patients' health needs;
      able to anticipate and cope with changes following graduation; committed to self
      improvement, willing to change to reflect best clinical practice; and equipped
      with skills for self-assessment and lifelong learning. This requires the
      appropriate balance of emphasis on educational content and educational process.
      This paper outlines the design considerations underlying the new BDSc curriculum
      at the University of Queensland. This curriculum uses an integrated rather than
      subject-based approach, with student-centred modes of learning as the principal
      learning style. Active learning strategies develop critical thinking and clinical
      problem-solving skills. Learning occurs in the context of a clinical situation
      (either overt or implied). Year 2 provides the major scientific foundations, and
      later years build upon this base, particularly through problem-based learning.
      Senior clinical staff involved in teaching in earlier parts of the course, help
      provide an overt clinical context to learning activities. The integrated
      curriculum model provides clinically relevant education in basic sciences and
      scientifically based education in clinical care. The curriculum has a focus on
      outcomes and on preparation for general practice. Importantly, it has an open and
      transparent structure, and each component is linked explicitly with the
      competencies expected of the new dental graduate.

PMID- 16894715
TI  - The legal environment and dentistry.

PMID- 16894716
TI  - [Systematics meanders of microsporidia].
AB  - Meanders of systematics of Microsporidia. Taxonomical questions of Microsporidia,
      its systematic position and evolutionary relationship with other Eukaryota are
      discussed. Utilizations of modern methods of investigations of microsporidians
      cause new taxonomical troubles. At the present time it is difficult to create a
      clear hypothesis concerning the phylogeny and evolution of Microsporidia. Most
      likely they are representatives of a new kingdom of Eukaryota. Existing problems
      will not be dissolved until new detailed data concerning the new and common
      species are obtained.

PMID- 16894717
TI  - [Nail plate susceptibility to Scopulariopsis brevicaulis infection].
AB  - Nail plate susceptibility to Scopulariopsis brevicaulis infection. Experimental
      Scopulariopsis brevicaulis infection of toe and finger nails collected from 79
      persons of both sexes and at various age is presented. Crumbled nail fragments
      were incubated with a S. brevicaulis strain isolated from toenail acauliosis. The
      culture was inspected and evaluated under light microscope after seven days of
      incubation. Hyphe intensively penetrating nail fragments were found in 67.1% of
      toenails and 38% of fingernails. The infection was most intensive in the nails
      collected from males and elderly persons.

PMID- 16894718
TI  - [Taxonomic, topical and quantitative structure of the community of intestinal
      flukes (Digenea) of mallards, Anas platyrhynchos Linnaeus, 1758 from the area of
      Szczecin].
AB  - Taxonomic, topical and quantitative structure of the community of intestinal
      flukes (Digenea) of mallards, Anas platyrhynchos Linnaeus, 1758 from the area of
      Szczecin. A total of 55 mallards (Anas platyrhynchos L.) from the area of
      Szczecin were examined for the presence of intestinal flukes (Digenea). This
      study covered the taxonomic structure (specific composition and taxonomic
      affiliation of the parasites), topical structure (parasites' distribution within
      the host's organism), and quantitative structure (infection intensity, abundance,
      prevalence, and infection index "Z"). Flukes were found in 69.1% of the birds
      studied. The highest intensity of infection and prevalence exhibited species of
      the family Echinostomatidae (Echinostoma revolutum, Echinostoma miyagawai,
      Echinostoma sp., Echinoparyphium recurvatum) and Notocotylus attenuatus of the
      family Notocotylidae. The mallards surveyed hosted 15 species of flukes,
      representing 6 families. Echinostoma miyagawai Ishii, 1932 has been found for the
      first time in Poland. The present findings of Psilotrema similium and
      Prosthogonimus ovatus in mallard constitute new host records for these parasites.

PMID- 16894719
TI  - Seasonal variation of parasite infection of three-spined stickleback
      (Gasterosteus aculeatus L.) in the southern Baltic.
AB  - Seasonal changes of infection were observed in the case of some species of
      ectoparasites: Trichodina domerguei domerguei, T. tenuidens, Gyrodactylus
      arcuatus, and Thersitina gasterostei, as well as for endoparasites: Glugea
      anomala, Schistocephalus solidus, Diphyllobothrium ditremum, and Proteocephalus
      filicollis. Same seasonal changes in frequency of developmental stages were
      observed in the case of females T. gasterostei. The highest level of infection
      with ectoparasites was observed in spring and summer and was probably an effect
      of increase of the reproductive activity with increase of temperature. Infection
      with tapeworms was generally low and was a result of feeding activity and fish
      diet.

PMID- 16894721
TI  - [Internal parasites of cattle in select Western Pomerania farms].
AB  - Internal parasites of cattle in select Western Pomerania farms. The studies were
      carried out in five farms, on 84 calves and 153 cows. The prevalence and
      intensity of the Coccidia and gastro-intestinal nematodes infection were
      determined by means of the Willis-Schlaafs and McMaster's methods. The Coccidia
      composition in the examined animals was determined by morphological features of
      the oocysts and the sporulation time. The following four Eimeria species were
      isolated: E. bovis, E. aubernensis, E. zurni and E. ellipsoidalis. Two methods
      were used for detection of Cryptosporidium sp. - the Ziehl-Neelsen staining
      technique and coproantigen test. In cows, the overall prevalence was Eimeria sp.
      ranged from 5.5 to 23.4%, gastro-intestinal nematodes ranged from 12.7 to 42.6%.
      In calves, the overall prevalence Eimeria sp. was ranged from 10.0 to 36.8%
      oocysts and Cryptosporidium sp. 22.8%.

PMID- 16894720
TI  - [Forming of gastro-intestinal nematodes fauna of free ranging European bison in
      Bialowieza Primeval Forest during last 17 years (1984-2001)].
AB  - 28 European bison of both sexes and in different age shot in Bialowieza Primeval
      Forest in January 1984, (10 animals), January 1992 (10 animals) and in January
      and the beginning of February 2001 (8 animals) have been necropsied. The examined
      animals in mentioned years were of similar age. There were examined abomasa and
      duodena of shot animals. All necropsied bison were infected with gastro
      intestinal nematodes. The highest intensity of infection with nematodes of
      abomasum was found in 1992 year and with nematodes of duodenum in 2001 year. In
      the examined period were found as many as 21 species of gastro-intestinal
      nematodes, and 15 of them occurred in 1984, 16 in 1992 and 17 in 2001; 12
      species, namely: Trichostrongylus axei, T. capricola, Ostertagia ostertagi, O.
      lyrata, O. leptospicularis, O. kolchida, Spiculopteragia boehmi, Cooperia
      oncophora, Nematodirus helventianus, N. roscidus, N. europaeus and Aonchotheca
      bilobata occurred in all 3 examined years. The highest mean intensity of
      infection and the percentage index of intensity of these 12 species of nematodes
      showed O. leptospicularis which was 45% to 47% of all Ostertagiinae. Beyond of
      these 12 species of nematodes which occurred in all examined years, there were
      found 9 species more: Ostertagia antipini, Spiculopteragia mathevossiani, S.
      asymmetrica, Mazamastrongylus dagestanicus, Cooperia surnabada, C. punctata, C.
      pectinata, Haemonchus placei and Ashworthius sidemi. They occurred sporadically
      and in low density. During the examined period, bison have adapted 10 species of
      parasites from Cervides. Mazamastrongylus dagestanicus - parasite primary typical
      for moose, was for the first time found in bison.

PMID- 16894722
TI  - Effect of different contents of proteins and vitamin B2 in the feed on the
      prevalence and infection intensity of Ascaridia galli in chickens.
AB  - A group of 10-day-old chickens was experimentally infected with a dose of 500
      infective eggs of Ascaridia galli (Schrank, 1788) (Nematoda). Forty-nine days
      post infection the chickens were necropsied and the infection intensity and
      prevalence were determined. The group maintained on the feed containing 11% of
      protein showed higher infection intensity and prevalence compared to the chickens
      fed a diet containing 19% of protein. The addition of vitamin B2 to the feed
      containing 11% protein resulted in lower intensity and prevalence of the
      infection. In both series of experiments no effect of Zn-bacitracin or vitamin B2
      on infection intensity or prevalence was observed for chickens fed feed
      containing 19% of protein.

PMID- 16894723
TI  - [The evaluation of Trichuris vulpis infection of stray dogs in Krakow area].
AB  - The evaluation of Trichuris vulpis infection of unwanted dogs in Krakow area. The
      aim of this work was the estimation of the infection with Trichuris vulpis of
      dogs in Cracow's Shelter for Stray Animals. A coprologic examination carried out
      between January and November 1999-2000 showed the prevalence of infection from
      6.8% to 15.1% and EPG from 88 to 913.

PMID- 16894724
TI  - [Prevalence of intestinal nematodes in dogs from Warsaw region].
AB  - Prevalence of intestinal nematodes in dogs from Warsaw region. Investigation of
      prevalence of intestinal parasites in dogs have been conducted in order to
      protect human and animal health. The aim of the study was to establish species
      composition of intestinal parasites and to evaluate their prevalence in dogs from
      the shelter in Jozefow situated on north from Warsaw. Additionally, urban dogs
      from Warsaw and village dogs from areas near the shelter, were examined. The
      prevalence of nematodes was: 62.3% in dogs from shelter, 37.5% in village dogs
      and 18.8% in urban dogs. In homeless dogs, the most common parasite was Uncinaria
      stenocephala, then Trichuris vulpis and Toxascaris leonina. In village dogs only
      eggs of U. stenocephala were detected; in urban dogs Toxocara canis and U.
      stenocephala were found.

PMID- 16894725
TI  - [The apoptosis in the course of experimental infection with T. pseudospiralis in
      mice].
AB  - The apoptosis in the course of experimental infection with T. pseudospiralis in
      mice. The level of apoptic cells in the lamina propria of the mucosa of the
      jejunum and in the masseter muscle in the mice infected with 200 larvae T.
      pseudospiralis was observed. Cryostat preparations made from jejunum and muscle
      samples on 7, 14, 21, 28, 60, 180 and 360 day post infection (dpi), were examined
      employing the TUNNEL method with the use of "In situ Cell Death Detection KIT
      Fluorescein" of Roche. The number of apoptic cells in the lamina propria of
      jejunum started to increase as early as on 7 dpi. The highest number of the
      apoptic cells, on an average - 56,4 in the crypta-villus unit, was recorded on 28
      dpi, whereas the return to the standard level took place only 360 dpi. The level
      of the apoptic cells in the masseter muscle was the highest on 28 and 60 dpi,
      which constituted some 30% of all the cells of infiltration.

PMID- 16894726
TI  - [Prevalence of multifocal fungal infections in patients undergoing permanent
      immunosuppresion after renal transplantation].
AB  - Prevalence of multifocal fungal infections in patients undergoing permanent
      immunosuppresion after renal transplantation. The aim of the study was to
      estimate the prevalence of fungi in monofocal and multifocal infections in renal
      transplant recipients. 32 renal transplant recipients were examined for presence
      of fungi in genital organs, oral cavity and rectum. Fungal strains were recovered
      in 66 out of 96 samples (68.2% off all renal transplant recipients) in oral
      cavity (65.6%), rectum (37.5%) and genital organs (25.0%) Monofocal mycosis was
      found only in 21.9% of the patients. Multifocal infections occurred in 68.2% and
      contained ontocenoses of oral cavity and rectum (34.4%) the most frequently.
      Trifocal infection (genital organs - oral cavity - rectum) occurred in 12.5% of
      all examined renal transplant recipients. The following fungi were found: Candida
      albicans (31 strains), C. glabrata (5), C. guilliermondii (2), C. krusei (2),
      Saccharomyces cerevisiae (1).

PMID- 16894727
TI  - [Characteristics of phenotypic specific and intraspecific features of fungal
      strains isolated from the organ ontocenoses in patients after renal
      transplantation].
AB  - Characteristics of phenotypic specific and intraspecific features of fungal
      strains isolated from the organ ontocenoses in patients after renal
      transplantation. The aim of present study was to describe 60 specific and
      intraspecific features of fungal strains isolated from the organ ontocenoses:
      oral cavity, rectum and genital organs in 32 patients undergoing permanent
      immunosupression after renal transplantation. Fungal strains identified using API
      20 C and API 20 C AUX (bioMerieux). The activity of 19 hydrolases was
      investigated using API ZYM. Among 41 strains of fungi the following were found:
      Candida albicans (31 strains), C. glabrata (5), C. guilliermondii (2), C. krusei
      (2) and Saccharomyces cerevisiae (1). The number of fungal strains isolated from
      the oral cavity was the highest (21), less numerous from rectum (12) and the
      least from the genital organs (8). The enzymograms were described for all strains
      and the highest activity was noted in case of: e6 - leucine arylamidase, e11 -
      phosphatase acid, e3 - esterase (C4), e12 - naphtol-AS-BI-phosphohydrolase. The
      activity of these enzymes is connected with higher pathogenicity of C. albicans
      strains.

PMID- 16894728
TI  - [Analyse of fungi prevalence and their species in the digestive tract of adult
      persons and children].
AB  - Analyse of fungi prevalence and their species in the digestive tract of adult
      persons and children. 1081 faecal sample were examined, 723 from adult persons
      and 358 from children. Fungal strains were recovered in 67.9% samples from adult
      persons and in 69.8% from children. There were found 8 species of fungi: Candida
      albicans, C. famata, C. tropicalis, C. krusei, C. glabrata, C. guilliermondii, C.
      kefyr, Saccharomyces cerevisiae.

PMID- 16894729
TI  - Candida albicans Berthout, 1923: hydrolases activity and own method of digestive
      tract strains biotyping.
AB  - 112 strains of Candida albicans were isolated from oral cavity and ontocenoses of
      the upper digestive tract (endoscopy) of children (age: 5-17) with
      gastrointestinal disorders. Axenic strains were differentiated with API 20C AUX
      and API ZYM tests (bioMerieux). Then enzymograms and biotypes were determined for
      all the strains based on the activity of 19 hydrolases. The highest activity was
      noted for: e2 - phosphatase alcaline, e6 - leucine arylamidase, e11 - phosphatase
      acid, e5 - lipase (c14); e7 - valine arylamidase, e12 - naphtol-AS-BI
      phosphohydrolase, e16 - alpha-glucosidase and e18 - N-acetyl-beta-glucosamidase,
      and the latter four were used for biotyping procedures. Our own system was based
      on the mathematical binominal distribution formula (1 : 4 : 6 : 4 : 1): all "+";
      one "-", three "+"; two "-", two "+"; three "-", one "+"; all "-". We have found
      the following biotypes: A (16.1 +/- 3.5%), B1 (2.7 +/- 2.53%), B3 (8.0 +/- 2.5%),
      B4 (22.3 +/- 3.9%), C2 (1.8 +/- 1.3%), C3 (7.1 +/- 2.4%), C6 (30.4 +/- 4.3%), D,
      (11.6 +/- 3.0%).

PMID- 16894730
TI  - [Scientific Life. Clinical Day of Medical Parasitology: "Trends in Diagnosis of
      Parasitologic Diseases and Mycoses" ].

PMID- 16894731
TI  - Stickleback as a potential paratenic host in the Anisakis simplex life cycle in
      the Baltic Sea: results of experimental infection.
AB  - Anisakis simplex stage 3 larvae found in herring were used to experimentally
      infect 155 sticklebacks and 6 nine-spined sticklebacks, caught in the Gdynia
      marina (Gulf of Gdansk). The larvae were observed in the fish body cavity as
      early as 24 h after infection, only the sticklebacks being affected. Altogether,
      50 live and 2 dead larvae were found in the stickleback body cavity. The
      infection prevalence and mean intensity were 13.6% and 2.4 larvae, respectively,
      from 1 to 8 larvae per fish being recorded. It is concluded that the stickleback
      may serve as a paratenic host for Anisakis simplex.

PMID- 16894732
TI  - [New/old opinions on the systematics and phylogenesis of the nematodes, with the
      special regard to Ascaridida, Ascaridoidea].
AB  - Traditional classification of the nematodes, based on morphological-ecological
      characters was evaluated in the context of molecular analysis of systematic
      taxons, with special regards to ascarids. Division of superfamily Ascaridoidea
      into 4 families (Heterocheilidae, Ascarididae, Anisakidae, Raphidascarididae)
      proposed by Fagerhholm (1991) seems to be proved by the molecular data of Nadler
      (1992, 1995) and Nadler & Hudspeth (1998).

PMID- 16894733
TI  - [Echinophthirius horridus (Olfers, 1816) (Anoplura) rare parasite on seals].
AB  - E. horridus of the Anoplura species was noted for the second time in Poland on a
      grey seal.

PMID- 16894734
TI  - Diphyllobothriosis--experimental study.
AB  - For the first time the agent of diphyllobothriosis Lake Baikal is the cestoda D.
      dendriticum establishted by T.P. Chizhova and P.G. Gofman-Kadoshnikov (1962). D.
      dendriticum reaches maturity in human intestine, but it is considered, that the
      relationships between the parasite and human are facultative property
      (Klebonovski 1985). The results of the investigation of the diet of sea-gull
      nestlings (control-uninfected and experimental-infected birds with cestoda
      groups) and stress influence (starvation) on the mass loss in experimentally and
      naturally infected ones with different duration conditions adaptation of
      experiments are discussed in this article.

PMID- 16894735
TI  - [The biological and anatomical-morphological properties of Hymenolepis diminuta
      tapeworms of WMS il1 and the WMS "strain"].
AB  - Crowded infrapopulations of H. diminuta obtained from the WMS il1 inbred line
      resembled those of the potentially non-inbred WMS strain in not showing either
      the abrupt reductions in the numbers of worms or the destrobilation described by
      other autors. Denser populations of both types of tapeworm have a greather
      abundance of 4 - testis proglottids of the 1p3a type (having 1 testis on the
      poral side and three on the aporal), and fewer of type 0p3a. Changes in the
      positioning of genital ducts and pores show a marked positive correlation with
      the abundance of type 2pla proglottids. Strobilae of H. diminuta WMS il1 contain
      a relatively greather number of type 0p3a proglottids and fewer of type 1p3a,
      than those of the WMS "strain"; something which is probably linked with the
      respective selection of the maternal tapeworms.

PMID- 16894736
TI  - Trichodina pediculus Ehrenberg, 1838 in roach Rutilus rutilus (L.), metric and
      meristic data.
AB  - During the parasitological studies in Dgal Wielki Lake 32 specimens of Trichodina
      pediculus were collected from roaches (Rutilus rutilus). T. pediculus were
      subjected to the metric and meristic measurements. High correlation factors
      significance was obtained between the following data: body diameter and adhesive
      disc diameter with border membrane, adhesive disc diameter without border
      membrane, denticulate ring diameter, height of denticle. However no correlation
      significance between body diameter and number of denticles was found.

PMID- 16894737
TI  - [Morphometric features of tarsus in Dermacentor reticulatus (Fabricius, 1794)
      (Acari: Ixodida: Ixodidae) larvae from Polish and Slovakian populations].
AB  - Dermacentor reticulatus is widely distributed dangerous tick that usually lives
      in the river valleys, boggy forests, meadows, and wooded pastures. Tick
      populations from various regions may exhibit morphological differences. In our
      study we compared morphometric features of tarsus in larvae D. reticulatus from
      Polish and Slovakian populations. I tarsus width, III tarsus length, and length
      of dorsal setae of I tarsus were significantly higher in Polish populations.
      Indices of width to length of tarsus I and tarsus III were also significantly
      different in both populations. The other examined morphologic features were
      similar, what may result from the same environmental conditions of both
      populations.

PMID- 16894739
TI  - [The concentration of trehalose and acitvity of trehalase from Galleria
      mellonella larvae infected by Steinernema affinis, Bovien 1937 (Nematoda:
      Rhabditida: Steinernematidae)].
AB  - The experimental studies were conducted on caterpillars of wax moth Galleria
      mellonella infected with Steinernema affinis larvae. The concentration of
      trehalose and the activity of trehalase were measured during the invasion lasting
      48h. The level of trehalose and activity of enzyme were slightly lower in
      infected insects in comparison to the control animals.

PMID- 16894738
TI  - [Toxicity of isolates of Bacillus thuringiensis from Wroclaw against larvae of
      Aedes aegypti].
AB  - Seven field isolates of Bacillus thuringiensis from the Lower Silesia, region of
      Poland, the Osola plain and phylloplane niches and soil samples from the
      Karkonosze National Park were tested in vitro for insecticidal activity against
      mosquito larvae Aedes aegypti. Both the spore/crystal mixture and pured crystals
      from B. thuringienis strains KpC1, KpF3 and OpQ3 (belonging to the first
      physiological group including the subspecies japonensis, yoso, jinghongiensis )
      proved to be the most active against insects (61-65% of corrected mortality). The
      lowest toxicity (7-28% mortality) was caused by B. thuringiensis wratislaviensis
      strains (PO12 and 13).

PMID- 16894740
TI  - [The enzymes of carbohydrates metabolism from Cysttidicola farionis
      (Cystidicolidae)].
AB  - The content of glycogen, glucose and trehalose was measured in larvae and adults
      of Cystidicola farionis, the parasite isolated from the swim bladder of Osmerus
      eperlanus from Vistula Lagoon. Activity of glycogen phosphorylase, alpha-amylase,
      glucoamylase, maltase, trehalase, and trehalose phosphorylase were measured. The
      highest activity was recorded for alpha-amylase 10.07 +/- 0.97 mu/mg and 7.47 +/-
      0.24 mu/mg, next maltase 1.34 +/- 0.63 micromol/mg and 2.06 +/- 1.65 micronol/mg
      respectively for larvae and adults. The activity of glucoamylase was nearly the
      same for adults and larvae (about 0.20 micromol/mg). The trehalase activity was
      higher at adults (0.49 +/- 0.42 micromol/mg) than at larvae (0.18 +/- 0.12
      micromol/mg). The activity of glycogen phosphorylase was much higher at larvae
      (3.58 +/- 1.49 micromol/mg) than at adults parasite (0.10 +/- 0.02 micromol/mg).
      The trehalose phosphorylase was present in both stages of parasite, but its
      activity was low. The content of glycogen and glucose was two-times higher in the
      adults' body than in larvae.

PMID- 16894741
TI  - Influence of the pH of the cultivation medium on survival and development of
      stage III larvae of Anisakis simplex.
AB  - The cultivation was done on Eagle's media as well as Eagle's media enriched with
      the supplement of 10 and 20% of bovine serum. In the media without serum the
      larvae lived significantly shorter and did not get through molting. They lived
      the longest and came through molting the fastest in the media with pH 2.0
      supplemented with 20% SB. In the media with the pH 4.0 and 7.3 the larvae lived
      significantly shorter and only a small proportion reached stage IV.

PMID- 16894742
TI  - [The comparison of properties of alpha-amylase from the third and fourth stage of
      Anisakis simplex larvae].
AB  - alpha-Amylase is present in the third (L3) and in the fourth-stage (L4) of larvae
      from Anisakis simplex. The enzymes from both sources differ in some of their
      properties. alpha-Amylase from L3 showed a maximum at pH 7.8, enzyme from L4
      stage at pH 6.5. The alpha-amylase from L3 was mainly lysosomal enzyme. The
      enzyme from L4 was located in the microsomal fraction. The L3 alpha-amylase
      showed the inhibition by EDTA and by -SH reagent iodoacetic acid. These agents
      did not change the activity of L4 enzyme. Both izoenzymes were unaffected by
      calcium and magnesium ions. Generally the alpha-amylase from L4 stage had higher
      activity (3.71 u/mg) than L3 one (2.29 u/mg).

PMID- 16894744
TI  - [The capability of deamination of aminoacids by selected strains of fungi].
AB  - We have studied the capability of dissociation of 22 L-form aminoacids by 27
      strains of fungi belonging to species: Candida, Cryptococcus, Geotrichum,
      Rhodotorula, Saccharomyces, Trichosporon. Fungal strains were cultured on agar
      medium with phenyl red and studied aminoacid. Disamination of an aminoacid by a
      fungus resulted in alkalisation of the medium and change of its colour from
      yellow to pink. Strains from genus Trichosporon and Geotrichum decomposed the
      most aminoacids (15-16), while fungi from genus Candida decomposed less aminoacid
      (1-8). Strains form species Candida famata, C. kefyr, C. lambica. C. rugosa, C.
      neoformans, R. mucilaginosa and S. cerevisiae did not show any ability to
      desaminate any of the 22 aminoacids used in the study. Aminoacids most frequently
      disaminated, by the studied strains of fungi included acidic aliphatic aminoacids
      and their amides: L-aspartic acid, L-asparagine, L-glutaminic acid, L-glutamine
      and neutral aliphatic aminoacids: L-glycin, L-alanine, L-serine. Aromatic and
      sulphur aminoacids (L-cysteine, L-cystine) were not decomposed by the studied
      fungal strains.

PMID- 16894743
TI  - [The cytochemical evaluation of activity of some oxidoreductases of Geotrichum
      candidum link under the influence of chemical compounds inhibiting the growth of
      the fungus].
AB  - It has been investigated, with the aid of routine cytochemical methods, whether
      any changes of the activity of oxydoreductases of G. candidum which has been
      influenced by chemical factors affecting its growth, and with which it can
      contact in human organism or his environment, occur. The factors were:
      antibacterial antibiotic from tetracycline group/chlortetracycline/, antifungal
      antibiotic representing polyenes derivatives/nystatine/, heavy metal
      salt/mercuric chloride/, aniline dye/malachite green/. To evaluate cytochemical
      preparates in which the fungus cells have been classified according to intensity
      of enzymatic reaction the chi2 test has been suggested. It has been proved that
      all the investigated compounds have significant changes in the fungus metabolism
      showing in the oxydoreductases activity deviations.

PMID- 16894745
TI  - [Contamination of dairy products by yeasts-like fungi].
AB  - Evaluation of the degree of contamination of diary products with potentially
      pathogenic fungal strains. Materials for the study were: yoghurt, cottage cheese,
      homogenised cottage cheese, cream and buttermilk. Differentiation of species was
      based on their morphological features and biochemical properties (API 20 C
      bioMerieux). Among 300 studied diary products we have isolated 100 (33.0 +/-
      2.72%) strains of yeast-like fungi. Diary products were contamined with 19
      species of fungi from types: Candida, Geotrichum, Trichosporon, Saccharomyces and
      Rhodotorula. The highest percentage of fungi was seen in cream (95.7 +/- 4.23%),
      cottage cheese (87.9 +/- 5.68%) and kefir (60.0 +/- 15.5%). In other studied
      products the frequency ranged from 13.1 +/- 2.54% to 35.2 +/- 6.51%. Among the
      isolated fungi the following species prevailed: Geotrichum candidum (18.0 +/-
      3.84%), Candida lusitaniae (15.0 +/- 3.57%) and C. inconspicua (11.0 +/- 3.13%).

PMID- 16894746
TI  - [Environment of school as potential place of interindividual transmissions].
AB  - The purpose of examinations was defined role of environment of school in
      interindyvidual transmisions. The yeast and yeast--like fungi isolated from the
      oral cavity, troat and nose from 270 healthy children, at the age of 6 to 15
      years, from country and municipal schools. The frequency of occurrence of fungi
      in country was higher than in minicipal schools by the resambling
      biodifferentiation. Totally 13 species belonging to 5 genera were detected in the
      examined material: Candida, Rhodotorula, Saccharomyces, Saccharomycopsis i
      Trichosporon. Increasing part of S. capsularis was noted in ontocenoses of
      healthy children. The qualitative and quantitative changes testify about changes
      of environment. Simultaneously, they inform about timely condition of mycoflora
      of the examined ontocenosis and surroundings.

PMID- 16894747
TI  - [Pediculosis in rural schools of Lublin Province].
AB  - The aim of the work was to study the prevalence of pediculosis capitis among
      schoolchildren in rural areas of Lublin Province in Eastern Poland and to examine
      its correlation with socio-economic conditions. A group of 42759 schoolchildren
      aged between 6 and 15 years from 52 rural primary schools were examined. The
      level of unemployment, number of physicians and number of nurses per 10000
      inhabitants were examined in the area of experiment. We achieved the following
      results: a total of 682 children were found to be infested with Pediculus humanus
      capitis, mean prevalence was 1.6%. The girls were more frequently infected than
      boys (75% for girls and 24% for boys). The children most frequently affected were
      those aged 6 (1.6%) and 8 to 12 years (1.6-2.1%). The children least affected
      were those aged 13 to 14 years (0.8-1.1%). The infestation rate was strictly
      correlated with the number of nurses per 10000 inhabitants. There was no
      relationship between the level of unemployment or the number of physicians and
      the infestation rate on experimental area. Our investigations seems to confirme
      that the prevalence of P. h. capitis is influenced by the level of primary health
      care, particulary quality of school nurses' work.

PMID- 16894748
TI  - [Preliminary analysis of the incidence rate of scabies in Lodz population].
AB  - We have analysed all the reported and diagnosed cases of scabies in the years
      1999-2000 per 100 000 inhabitants in the Lodz voivodeship. The data was obtained
      from the Regional Administration Unit for the Control of Epidemics and Hygiene
      Promotion in Lodz. The incidence in Lodz voivodeship was found to be twice as
      high (89,0) as that in Poland (44,0). The highest incidence in Lodz voivodeship
      was found in Radomsko (268,0), Pabianice (149,0) and Kutno (148.5) districts. The
      number of new cases registered in 1999-2000 did not increase in the districts:
      Leczyca, Radomsko, Lowicz and Belchatow.

PMID- 16894749
TI  - [Analysis of different clinical criteria in malaria patients in Papua New
      Gwinea].
AB  - To assess the validity of different clinical criteria in malaria patients, a
      small study including 92 children presented with fever or history of fever were
      examined in a highly endemic area of Papua New Gwinea. In 21 children
      parasitaemia was confirmed by microscopy examination of thick and thin smear
      stained with Giemsa method (9 cases of Plasmodium falciparum, 8 cases of
      Plasmodium vivax and 4 cases of mixed invasion Plasmodium falciparum and
      Plasmodium vivax). Only 4 from different 39 criteria analyzed in children with
      history of fever or hot skin showed significant association with parasitaemia
      (conscious disturbances, severe wasting, enlarged spleen and diarrhoea), however
      none of the criteria presented high sensitivity and could serve as good
      predictors for parasitaemia accept two (first and second one). These findings
      help to realize the importance of laboratory examination in diagnosis of malaria
      and explain difficulties in confirming or exclusion of malaria where microscopy
      is not available.

PMID- 16894750
TI  - [The cases of infection of brown rats Rattus norvegicus with Trypanosoma lewisi
      (Kent, 1880) Laveran i Mesnil, 1901, in the area of Warsaw agglomeration].
AB  - Two from three brown rats (Rattus norvegicus) catched in Milan6wek near Warsaw,
      and one catched in the centre of Warsaw were infected with Trypanosoma lewisi.
      The morphometric features of trypanosomes were in accordance with the features of
      T. lewisi gived by other authors. This is first note about infection of free
      living rats with T. lewisi in Poland.

PMID- 16894751
TI  - [The prevalence of trypanosomes in bream Abramis brama in Goslawskie and Goplo
      lakes].
AB  - 20 individuals of Abramis brama from Goslawskie Lake and 10 individuals from
      Goplo Lake, central Poland, were investigated on the presence of trypanosomes.
      The infections of Trypanosoma abramidis LAVERAN and MESNIL, 1904 were detected in
      three breams from Goslawskie Lake and two in Goplo Lake. The question of the
      distinctivity of T. abramidis from T. carassii Mitrophanow, 1883 found in other
      Cyprinidae in Poland is discussed.

PMID- 16894752
TI  - [Seasonal activity of the ticks Ixodes ricinus in the lakesides and forests
      habitats of Szczecin and environs and its infestation with the spirochete
      Borrelia burgdorferi].
AB  - The article presents the results of researche (1999-2000) on numbers and seasonal
      activity of Ixodes ricinus in selected lakesides and forests habitats of Szczecin
      and on occurence of the spirochetes Borrelia burgdorferi sensu lato in ticks. A
      total of 8065 ticks were collected from 6 localities : 647 larvae, 4549 nymphs,
      1624 females and 1244 males. The spirochetes B. burgdorferi were found (using the
      PCR techniques) in 2271 specimens e.c. 28.1% whole population. Numbers infected
      larvae were 216 (33.4%), nymphs 1215 (26.7%), females 490 ( 30.6%), males 350
      (28.1%). This study shows that examinated habitats where I. ricinus is present
      are risk areas of human infection with Lyme disease spirochaetes.

PMID- 16894753
TI  - [Toxocarosis in the Lodz region over the years 1996-2000].
AB  - In the paper epidemiologic analysis of toxocarosis with socio-medical background
      in humans in the Lodz macroregion over the years 1996-2000 was carried out. It
      was found that 58.2% of toxocarosis cases represent asymptomatic invasions
      occurring more often in town residents. The clinical form "minor" pertained the
      country residents, patients of elementary education and the group "pupil
      student". The "major" form of toxocarosis was found in the country residents,
      young people, and patients over 60 years old.

PMID- 16894754
TI  - [Distribution of sources of Toxocara spp. infection in urban and rural
      environments in Poland].
AB  - Soil examinations made in 5 regions of Poland in the 1990s comprised 1184 samples
      taken from urban areas and 590 samples from suburban and rural areas. Toxocara
      spp. eggs were found more often in urban areas (14% positive samples) than in
      suburban and rural once (12% positive samples). The average ratio of positive
      samples was: in the streets and roads--19.3% (0.36 eggs/100g of soil), near
      houses (backyards, gardens)--18.6% (1.11 eggs/100g), in sandpits--13.0%
      (0.23/100g), in parks and public gardens--10.5% (0.46 eggs/100g), on playgrounds
      and playing fields 9,4% (0,06 eggs/100g) and on the beaches--3.4% (0.03
      eggs/100g). In children habitual play areas the prevalence of T. cati eggs was
      higher than T. canis eggs.

PMID- 16894755
TI  - [Intestinal parasitoses on the basis of own investigations].
AB  - In the period 1997-2000 3968 samples were examined. Parasitological material came
      from 3 174 children and 794 adults. Infection with intestinal protozoan and
      helminthes was noted in 80.2% of children as well as in 18.5% of adults (to 65
      year old) and in 1.3% of patients over 65 year old. Among the children the most
      often were eggs of Enterobius vermicularis (detected by tongue depressor covered
      with a transparent adhesive tape) and Giardia lamblia (diagnosed on the detection
      of coproantigens GSA 65--commercial kits). Every year the detection of G. lamblia
      in children was the highest in the autumn-winter months what proved the summer
      infections. E. vermicularis occurred more often than G. lamblia however without
      the seasonal peaks.

PMID- 16894757
TI  - [Occurence of gastrointestinal parasites in children in Lublin region in the
      period 1976 - 2000].
AB  - From 1976 to 2000, were examined 2828 children for the presence of
      gastrointestinal parasites. Investigations were made by means of a standard
      coprological methods, Graham's method and immunoenzymatic method (Prospect
      Giardia) for the presence of coproantigen of Giardia. The following parasites
      were detected in 1299 children: Giardia lamblia 1.3%, Ascaris lumbricoides 3.0%,
      Trichuris trichiura 7.8%, Enterobius vermicularis 40.5%. The parasites were found
      most frequently in children from a home for mentally handicapped. The number of
      infected among children inhabiting country was higher than among those from the
      towns. There was no significant difference between boys and girls.

PMID- 16894756
TI  - [Infection of red deer with lung nematodes in Polish and Belorussian parts of
      Bialowieza Forest].
AB  - Fecal samples from red deer from polish and belorussian parts of Bialowieza
      Forest were examined by Baermann method. First stage larvae of three species of
      lung nematodes were found. In polish part in 100% of samples were larvae of E.
      cervi, in 50% V. sagittatus and in 21% D. noerneri, and in belorussian the level
      of infection was lower and larvae were in 92%, 36% and 12% of samples
      respectively. In significant part of samples were met mixtured invasion of two or
      three species. Finding of larvae of E. cervi is the first registration of this
      species in belorussian part of Bialowieza Forest, and V. sagittatus is a new
      species for the fauna of Byelorussia. Nematodes E. cervi are dangerous for
      domestic ruminants.

PMID- 16894758
TI  - [The studies of the invasion of Alaria alata (Goeze,1782) in the Province of
      Kuyavia and Pomerania].
AB  - The studies were conducted between 1999 and 2001 in two hunting regions. Larval
      alariosis was revealed in the boars only in one of the studied regions. In this
      region, the results of the parasitological studies, conducted towards A. alata in
      the direct host (domestic dogs) and indirect hosts (snails: Planorbis planorbis
      and Anisus vortex as well as frogs: Rana temporaria and Rana terrestris) were
      also positive. The lack of the host snails A. alata in the other region might
      have resulted from no presence of the parasite in the boar.

PMID- 16894759
TI  - [The case of dermatitis in the human as a result of the influence of the cercaria
      of the bird schistosome].
AB  - There are numerous cases of dermatitis described world-wide and resulting from
      the influence of the furcocercaria of the bird schistosome. The host snail
      species of the schistosome, producing thousands of furcocercaria are common in
      our country. But, because of too general symptoms of dermatitis resulting from
      the influence of the schistosome of the larvae, there are many unrecognisable
      cases. The reaction described was typical of a twenty-seven-year-old man
      collecting snails in the Piechota Bay in Gostynin (the Province of Kuyavia and
      Pomerania). In that reservoir, individuals of Lymnaea stagnalis were found, which
      were infected with sporocysts and furcocercaria of Trichobilharzia ocellata. In
      the laboratory conditions, a high expulsion of cercaria was observed, which
      amounted to over 8000 larvae per snail.

PMID- 16894760
TI  - [Usefulness of the molecular techniques for detecting and/or identifing of
      parasites and fungi in humans and animals or pathogens transmitted by ticks (Part
      I)].
AB  - After a long period of using basic microscopic, immunological and biochemical
      methods for diagnosis, rapid development of nucleic acids investigation enabled
      introduction of specific and sensitive methods of detection of pathogenic agents
      on the molecular level. Among others, polymerase chain reaction (PCR), discovered
      in mid of 80'ies and then automatized, offered an attractive alternative to
      conventional testing systems. In this paper we describe reliable diagnostic tests
      widely used in the world, including Poland, and capable of detecting different
      disease agents as parasites and fungi in clinical specimens and pathogens of
      emerging zoonotic diseases in ticks. The possibilities of using molecular methods
      for determination of Plasmodium falciparum drug resistance is also discussed.
      Moreover, the report offers information concerning kinds of molecular tests and
      institutions in which there are executed.

PMID- 16894762
TI  - [Usefulness of the molecular techniques for detecting and/or identifing of
      parasites and fungi in humans and animals or pathogens transmitted by ticks. Part
      III].

PMID- 16894761
TI  - [Usefulness of the molecular techniques for detecting and/or identifing of
      parasites and fungi in humans and animals or pathogens transmitted by ticks. Part
      II].

PMID- 16894763
TI  - [Clinical value of Echinococcus granulosus--specific immunoglobulin G antibody
      avidity in liver cystic echinococcosis].
AB  - Role of E. granulosus-specific IgG antibody avidity in evaluation of a natural
      history of the parasite cysts in the liver, duration of infection and immunogenic
      cysts activity was studied. Thirty-one patients with liver cysts suspected of
      echinococcosis were examined; E. granulosus infection was finally confirmed by a
      fine needle aspiration biopsy or surgery in 29 cases (93.5%) and two non
      parasitic simple cysts in the liver were diagnosed. E. granulosus-specific IgG
      antibody was found in 21 patients (67.7%). High IgG avidity values were observed
      in 14 patients with liver cysts in a degeneration stage confirmed by imaging
      techniques. Low IgG avidity values were mostly detected in children with
      hypoechogenic echinococcal cysts being in a recent stage of infection.
      Determination of anti-E. granulosus immunoglobulin G antibody avidity is a very
      usefull diagnostic tool for a determination of parasitic cysts activity and their
      developmental age.

PMID- 16894764
TI  - [Parasitological examinations of the hydatoid cysts of liver].
AB  - Liver cysts taken from 9 patients, operated on in the Medical Academy Clinic in
      2000, have been examined. Cyst layers, their thickness and content have been
      analysed. We have searched for the cestoid scolexes and rostellar hooks. In 6
      patients Echinococcus granulosus larvae have been found. In 4 cases there have
      been protoscolexes discovered, however with some signs of degeneration of the
      larva. In one case dead larva has been diagnosed on the basis of the presence of
      single hooks and in one patient one larva alive with unchanged structures has
      been revealed. Profound parasitological examination is a good supplement to the
      examination of the histopathological slides, especially in the case of
      degenerating larvae, when the tissues of the parasite lose their contact with the
      connective tissue layer of the host. Separated layer fragments, as well as
      protoscolexes and rostellar hooks need not be exposed to histological cutting.

PMID- 16894765
TI  - [Enhancement of laboratory diagnosis specificity in human toxocariasis].
AB  - The aim of the study was to enhance specificity of immunological diagnosis in
      toxocarosis. The investigations concern: detection of circulating parasite
      antigens using dot-ELISA technique and detection of specific IgG antigodies using
      ELISA test with low molecular weight (< or = 30 kD) excretory-secretory (ES)
      larval T. canis antigens. The circulating antigens were investigated in 60 sera
      and 20 anterior chamber fluids from children with ocular form of toxocarosis.
      These antigens were present only in 3 sera and 2 anterior chamber fluids in
      children with active intraocular inflamation and fluid antibodies titers 1:5120
      and 1:20 000. Comparative study with different ELISA tests indicated that use of
      low molecular weight antigens increase specificity of reaction.

PMID- 16894766
TI  - [Development of the ELISA kit for the detection of Hypoderma bovis antibodies in
      cattle. I. Development of components].
AB  - The aim of these investigations was to prepare the antigen and control sera for
      the ELISA. Positive control sera were obtained from 163 cows showing clinical
      symptoms of H. bovis infection and negative control sera from 60 cows free from
      the infection. The antigen for the ELISA was obtained from H. bovis L1 larvae.
      Three basic fraction were isolated from whole excreted/secreted antigen by
      elution from gel and by preparative isoelectrofocusing. Using the Western
      Blotting method it was demonstrated that Hy A (22-24 kDa and pI 4-5) had the best
      antigenic property. As can be seen from these investigations the developed ELISA
      kit for the detection of H. bovis antibodies in cows is highly specific and
      sensitive.

PMID- 16894767
TI  - [Development of the ELISA kit for the detection of Hypoderma bovis antibodies in
      cattle. II. Setting the best terms for collecting blood samples for the
      laboratory diagnosis of hypodermyiasis in different regions of Poland].
AB  - The experiments were carried out on 285 cows from 10 herds from different regions
      of Poland. Extensity of the H. bovis invasion in each herd varied from 10 to 86%.
      The highest extensity appeared in herds from eastern and north-eastern Poland and
      the lowest in herds from southern and central regions of the country.
      Seroconversion of Hypoderma bovis antibodies was calculated for animals in which
      warbles were detected by clinical examination. The highest serum densities were
      observed in herds in March, April and May. The results of these investigations
      demonstrated that the best term for collecting blood samples to examine cattle
      for hypodermosis is the winter-spring season.

PMID- 16894768
TI  - [Development of the ELISA kit for the detection of Hypoderma bovis antibodies in
      cattle. III. Stability and usefulness of ELISA components preserved under
      different conditions].
AB  - The aim of investigations was to determine the stability of ELISA components
      preserved under different conditions. The following components for the ELISA were
      used: the secreted/excreted antigen prepared from H. bovis L1 larvae, its
      fraction containing hypodermine A, conjugat, positive and negative control sera.
      Freezing at -20 degrees C, lyophilization and preservation at 4 degrees C were
      applied. Seven kits for the ELISA containing components preserved using described
      methods, were prepared. The identical packets of sera were examined by the ELISA
      directly after preparation of the kits (day '0'), and next, at 3-4 week intervals
      for 9 months. The experiments showed that the best method of conservation of
      ELISA components for the detection of H. bovis antibodies was lyophilization. The
      kits prepared in this way did not lose their characteristics for 9 months and
      their specificity and sensitivity were close 100%.

PMID- 16894769
TI  - [Nested PCR in the diagnosis of Pneumocystis carinii pneumonia (PCP) in AIDS
      patients].
AB  - The studies were undertaken to evaluate the usefulness of a nested PCR assay in
      the diagnosis of Pneumocystis carinii pneumonia (PCP) in AIDS patients. To
      achieve the end, 51 excretions samples from the respiratory tract were collected
      from HIV-infected patients with respiratory symptoms, and examined for the
      presence of specific DNA. A portion of the mitochondrial large-subunit rRNA gene
      of Pneumocystis carinii was amplified with outer primers pair pAZ 102E, pAZ 102H
      and internal primers pAZ 102X, pAZ 102Y. Positive nested PCR results were
      obtained with 36 out of 51 examined samples. Some 52.8% of the positive results
      were obtained with samples collected from patients without clinical diagnosis of
      PCP. It was concluded, that the nested PCR method, being too sensitive, is not
      suitable for the routine diagnosis of PCP in AIDS patients.

PMID- 16894770
TI  - [Babesosis--difficulty of diagnosis].
AB  - Human babesiosis is caused predominantly by B. microti and B. divergens, a
      protozooan parasites of red blood cells. Both are transmitted by Ixodes ricinus
      ticks, also the primary vector of Lyme disease. Clinical manifestation varied
      widely from asymptomatic infection to a serve rapidly fatal disease. The
      diagnosis of babesiosis include examination of stained blood smers, serological
      evaluation indirect antibody tests and PCR. With the evolution PCR--based
      techniques, the diagnosis and monitoring of babesial infections became more
      sensitive and reliable.

PMID- 16894771
TI  - [Magnetic resonance imaging and spectroscopic metabolites assessment in brain
      cryptococcosis].
AB  - Cryptococcus neoformans is the causative agent of cryptococcosis and cryptococcal
      meningitis, which are serious pathological conditions affecting up to 10% of
      patients with AIDS. In this paper we present results magnetic resonance imaging
      and spectroscopic metabolites (1H MR) in brain cryptococcosis. In 1 HMR
      spectroscopy we find decreased metabolic ratios to nonsaturated water (H2O)
      signal N-acetylaspartate (NA/H2O, creatine (Cr/H20), choline (Cho/H2O). We show
      increased mioinositol to H2O ratio. Spectroscopy results suggest about massive
      neuronal injury and accompanying gliosis in brain cryptococcosis.

PMID- 16894772
TI  - [The estimation of Pneumocystis carinii in HIV-infected patients occurrence based
      on three different methods].
AB  - The frequency of Pneumocystis carinii occurrence in BAL of 38 HIV-infected
      patients was determined with three different method. BAL sediments were stained
      with Giemsa method, silvered according to Gomori-Grocott method and studied with
      indirect immunofluorescence assay. Using Giemsa method staining Pneumocystis
      carinii was diagnosed in 81.6% of patients, in Gomori-Grocott method--in 31.6% of
      patients, but results of indirect immunofluorescence assay were positive only in
      23.,7%. In our study staining BAL sediments with Giemsa method allowed to detect
      Pneumocystis carinii in the highest percentage of examined patients.

PMID- 16894774
TI  - Chromatographic chiral separations.

PMID- 16894773
TI  - Stem cell central.

PMID- 16894775
TI  - HPLC separation of amino acid enantiomers and small peptides on macrocyclic
      antibiotic-based chiral stationary phases: a review.
AB  - The search for new and effective chiral selectors capable of separating a wide
      variety of enantiomeric compounds is an ongoing process. In the past decade,
      macrocyclic antibiotics have proved to be an exceptionally useful class of chiral
      selectors for the separation of enantiomers of biological and pharmacological
      importance by means of HPLC, TLC and electrophoresis. More chiral analytes have
      been resolved through the use of glycopeptides than with all the other
      macrocyclic antibiotics combined (ansamycins, thiostrepton, aminoglycosides,
      etc.). The glycopeptides avoparcin, teicoplanin, ristocetin A and vancomycin have
      been extensively used as chiral selectors in the form of chiral bonded phases in
      HPLC, and HPLC stationary phases based on these glycopeptides have been
      commercialized. Teicoplanin, vancomycin, their analogs and ristocetin A seem to
      be the most useful glycopeptide HPLC bonded phases for the enantioseparation of
      proteins and unusal native and derivatized amino acids. In fact, the macrocyclic
      glycopeptides are to some extent complementary to one another: where partial
      enantioresolution is obtained with one glycopeptide, there is a high probability
      that baseline or better separation can be obtained with another. This review sets
      out to characterize the physicochemical properties of these antibiotics and their
      application in the enantioseparations of amino acids. The mechanism of
      separation, the sequence of elution of the stereoisomers and the relation to the
      absolute configuration are also discussed.

PMID- 16894776
TI  - Recent developments in the HPLC enantiomeric separation using chiral selectors
      identified by a combinatorial strategy.
AB  - Two kinds of chiral stationary phases (CSPs) can be distinguished: (i) the
      "conventional" CSPs for which the selectivity is not pre-determined and (ii) the
      CSPs which are characterized by a predictable elution order, depending on the
      target enantiomer used for the selection of the chiral selector. At the present
      time, three general methodologies have been described to create chiral selectors
      specifically designed against the racemate to resolve: the molecular imprinting
      technology, the production of antibodies and the combinatorial approach. The
      latter methodology involves two categories of procedures to develop CSPs: an
      approach from a small library of low-molecular weight selectors and an approach
      from a very large library of single-stranded oligonucleotides (DNA and RNA
      aptamers). In this review, the recent advances in the HPLC applications of the
      chiral selectors identified through these two combinatorial procedures are
      addressed.

PMID- 16894778
TI  - Comparison of monolithic approaches for enantioselective capillary
      electrochromatography involving cyclodextrins.
AB  - The access to CD-modified monoliths for enantiomeric separation by CEC can be
      divided into two main approaches. (i) Silica-based monoliths, prepared by either
      a sol-gel process or by sintering of silica particles, are modified after
      fabrication by coating with a CD selector. Alternatively the fusion of CD
      functionalized silica particle via gluing is feasible. (ii) Rigid or homogeneous
      organic polymer-based monoliths, prepared by polymerization of organic monomers
      in the presence of a porogen, are modified with the CD selector either by
      copolymerization or by physical incorporation into the continuous bed.

PMID- 16894777
TI  - Monolithic enantiomer-selective stationary phases for capillary
      electrochromatography.
AB  - Monolithic materials have become a well-established format for stationary phases
      in the field of capillary electrochromatography. Four types of monoliths, namely
      particle-fixed, silica-based, polymer-based, and molecularly imprinted monoliths,
      have been utilized as enantiomer-selective stationary phases in CEC. This review
      summarizes recent developments in the area of monolithic enantiomer-selective
      stationary phases for CEC. The preparative procedure and the characterization of
      these columns are highlighted. In addition, the disadvantages and limitations of
      different monolithic enantiomer-selective stationary phases in CEC are briefly
      discussed.

PMID- 16894780
TI  - Enantiomeric separation of chiral sulfoxides by supercritical fluid
      chromatography.
AB  - The application of supercritical fluid chromatography (SFC) to the enantiomeric
      separation of several chiral sulfoxides belonging to the family of the
      substituted benzimidazoles, including omeprazole, lansoprazole, pantoprazole,
      rabeprazole, oxfendazole and ricobendazole, is presented in this work. The column
      employed was Chiralpak AD and the effect of different chromatographic conditions
      was studied. The results obtained showed that all the compounds can be
      enantiomerically resolved using SFC, with resolutions higher than 2 and analysis
      times that in most cases were lower than 10 min. Alcohol type modifiers provided
      the best results, with ricobendazole, oxfendazole, and omeprazole showing the
      highest retentions and resolutions. Study of the temperature effect revealed
      that, in general, the isoelution temperature was above the temperatures assayed,
      except in the cases of omeprazole, lansoprazole, and oxfendazole with ethanol as
      modifier and pantoprazole with acetonitrile. Enthalpy-entropy compensation could
      also be demonstrated for the retention of the first and second eluted enantiomers
      as well as for the selectivity, with compensation temperatures of 25 degrees C,
      45 degrees C, and 83 degrees C, respectively. Reversal of elution on change of
      the organic modifier was only observed for omeprazole using 2-propanol.

PMID- 16894779
TI  - Chiral separation strategy in polar organic solvent chromatography and
      performance comparison with normal-phase liquid and supercritical-fluid
      chromatography.
AB  - A strategy, including a rapid screening and several optimisation steps, for the
      separation of chiral molecules of pharmaceutical interest by polar organic
      solvent chromatography (POSC), using four polysaccharide-based stationary phases,
      is proposed and compared with previously reported strategies in normal-phase
      (NPLC) and supercritical fluid chromatography (SFC). In a first part of this
      paper, different examples demonstrate the effectiveness of the POSC strategy for
      fast method development. Optimisation is based on the use of experimental design
      to map the experimental domain in an efficient way. In the second part, the best
      screening results, obtained after performance of earlier defined chromatographic
      screening strategies in NPLC and SFC, are compared to those obtained in POSC. The
      three techniques show complementary separation results and allowed baseline
      separation of 23 of 25 compounds. POSC is found to be a very interesting
      separation mode compared to NPLC, because of the many fast (< 10 min) baseline
      separations obtained.

PMID- 16894781
TI  - Enantiomeric resolution of bifonazole by supercritical fluid chromatography.
AB  - The enantiomeric separation of bifonazole by supercritical fluid chromatography
      on Chiralpak AD has been studied. The effect of different modifiers (methanol,
      ethanol, 2-propanol, and acetonitrile) was examined. Enantioseparation was
      possible with all of them, but the best results were provided by the alcohol-type
      ones. The resolution was higher than 5 in all cases. The isoelution temperatures
      Tiso were calculated from the study of the temperature effect for the different
      organic modifiers. The value of Tiso was below the working temperature range on
      using methanol, but above it with ethanol or 2-propanol.

PMID- 16894782
TI  - Optimisation of the derivatization in cellulose-type chiral selectors for
      enantioseparation by centrifugal partition chromatography.
AB  - Cellulose was chemically modified with hydrophobic dodecanoyl groups followed by
      3,5-dimethylphenylcarbamoyl substituents forming mixed ester/carbamate
      derivatives in order to improve the solubility in lipophilic solvents compared to
      the corresponding homosubstituted cellulose tris(3,5-dimethylphenylcarbamate).
      Two mixed derivatives of different degree of substitution were prepared, tested
      as chiral selectors (CSs) in counter-current chromatography (CCC) and compared to
      the homo-substituted derivative. Alternatively, cellulose tris(3,5
      dichlorophenylcarbamate), was synthesised and tested with the same purpose. The
      racemic drugs pindolol and warfarin were used as test compounds. Biphasic
      organic/aqueous solvent systems, composed of methyl isobutyl ketone, t-butyl
      methyl ether or ethyl acetate and aqueous ammonium acetate or sodium phosphate
      buffer, were used. Centrifugal partition chromatography, a variety of CCC, in the
      classical elution mode and the pH-zone-refining displacement mode was applied.
      The enantioseparation of pindolol and warfarin was achieved in the latter
      conditions. The presence of dodecanoyl chains on the CS increased solubility in
      the organic solvents used. The selectivity of the mixed dodecanoyl/3,5
      dimethylphenylcarbamoyl cellulose derivative with low degree of dodecanoyl groups
      (degree of substitution 0.3/degree of substitution 2.6, respectively) was similar
      to that of the homo-substituted derivative. Furthermore, the loading capacity for
      pindolol was increased by a factor of three compared to cellulose tris(3,5
      dimethylphenylcarbamate). Nevertheless, the increasing degree of substitution
      with dodecanoyl groups on the CS, although improved solubility in the stationary
      phase, contributed negatively to the enantioselectivity, where warfarin was more
      affected than pindolol.

PMID- 16894783
TI  - Chiral discrimination of primary amines by HPLC after labeling with a chiral
      derivatization reagent, trans-2-(2,3-anthracenedicarboximido)-cyclohexanecarbonyl
      chloride.
AB  - Enantiomeric discrimination of chiral primary amines was performed by both
      reversed-phase HPLC and normal-phase HPLC after labeling with a chiral
      fluorescent derivatization reagent, (1R,2R)- and (1S,2S)-trans-2-(2,3
      anthracenedicarboximido)cyclohexanecarbonyl chloride. Use of HPLC permits
      separation of diastereomeric derivatives of amines up to C30 which have a primary
      amino group at the middle of the alkyl chain. The derivatives of primary amines
      having an anteiso alkyl chain, which has a chiral branched-methyl at the n-3
      position of the alkyl chain, were also separated by HPLC, and it was also
      possible to separate niphatesine D by reversed-phase HPLC after derivatization.

PMID- 16894784
TI  - Analytical and semipreparative high performance liquid chromatography separation
      of stereoisomers of novel 3,4-dihydropyrimidin-4(3H)-one derivatives on the
      immobilised amylose-based Chiralpak IA chiral stationary phase.
AB  - Direct HPLC separation of stereoisomers of three novel 5-methyl-2-(alkylthio)-6
      (2,6-difluorophenylalkyl)-3,4-dihydropyrimidin-4(3H)-ones endowed with antiviral
      and potential antiproliferative and morphological differentiation activity
      against melanoma cells was performed by using the new immobilised amylose-based
      Chiralpak IA chiral stationary phase. Stereoselective conditions were achieved
      using normal phase eluents containing "non-standard" solvents such as ethyl
      acetate, methyl tertbutyl ether, or dichloromethane. In order to study the
      chiroptical properties of single stereoisomers, mg-scale separations were
      performed on analytical and semipreparative size Chiralpak IA columns in
      combination with ethyl acetate-based eluents.

PMID- 16894785
TI  - Extended application of a chiral stationary phase based on (+)-(1 8-crown-6)
      2,3,11,12-tetracarboxylic acid to the resolution of N-(substituted benzoyl)-alpha
      amino acid amides.
AB  - A chiral stationary phase (CSP 1) based on (+)-(18-crown-6)-2,3,11,12
      tetracarboxylic acid was applied to the resolution of N-(substituted benzoyl)
      alpha-amino acid amides and esters. N-(Substituted benzoyl)-alpha-amino acid
      amides were well resolved using a mixture of acetic acid-triethylamine
      acetonitrile (0.01:0.05:100, v/v/v) as an optimum mobile phase while N
      (substituted benzoyl)-alpha-amino acid esters were not resolved at all. In
      contrast, both N-(substituted benzoyl)-alpha-amino acid amides and esters were
      not resolved at all or resolved very poorly on another CSP (CSP 2), which lacks
      the two N-H hydrogens of the amide tethers of CSP 1. Among the substituents on
      the benzoyl group of analytes, the nitro group was the best for good resolution
      of analytes on CSP 1. From these results, the two N-H hydrogens of the amide
      tethers of CSP 1, the carbonyl oxygen of the amide group of analytes, and the
      nitro group on the benzoyl group of analytes were concluded to play significant
      roles in chiral recognition. In addition, various N-(3,5-dinitrobenzoyl)leucine
      amides with different lengths of N-alkylamide chains were resolved on CSP 1 and N
      (3,5-dinitrobenzoyl) leucine N-propylamide was found to show the best chiral
      recognition in terms of the separation (alpha = 1.30) and the resolution factor
      (Rs= 3.17).

PMID- 16894786
TI  - Evaluation of a hydrazide-linked alpha1-acid glycoprotein chiral stationary
      phase: separation of R- and S-propranolol.
AB  - The binding and chiral separation of R- and S-propranolol was investigated on a
      new type of alpha1-acid glycoprotein (AGP) column. This column was prepared
      through the controlled and mild oxidation of AGP, followed by the immobilization
      of this protein to hydrazide-activated silica. The effects of temperature, pH,
      ionic strength, and organic modifiers on the retention and separation of R- and S
      propranolol were investigated on this column. Both the association equilibrium
      constants and number of binding sites for R/S-propranolol on the AGP column were
      found to increase with temperature and affect the measured retention factors for
      these compounds. Regarding the other factors, a change in the organic modifier
      concentration was found to give the largest change in retention and separation.
      It was found through these studies that both coulombic and hydrophobic
      interactions played important roles in determining the retention of R- and S
      propranolol on the AGP column. The efficiency and separation impedance of this
      system were also considered. Under the final optimum conditions identified in
      this study, it was possible to separate R- and S-propranolol with a resolution of
      greater than 1.38 in less than 5 min on a 4.1 mm I.D. x 5 cm column.

PMID- 16894787
TI  - Use of tert-butylbenzoylated tartardiamide chiral stationary phase for the
      enantiomeric resolution of acidic compounds by nano-liquid chromatography.
AB  - Several racemic acidic compounds of pharmaceutical and environmental interest
      have been separated into their enantiomers by nano-liquid chromatography (nano
      LC) employing a tert-butylbenzoylated tartardiamide chiral stationary phase (CHI
      TBB). CHI-TBB was packed into a fused silica capillary of 100 microm id and
      retained by two frits made with a heated wire; detection was on-column at a
      window (about 0.5 cm) prepared by removing the polyimide layer. The normal phase
      mode was selected for eluting the studied acidic compounds and therefore n
      hexane/2-propanol/acetic acid (89/10/1, v/v/v) was used as mobile phase. Working
      at a flow rate of 220 nL/min a good resolution was obtained for mecoprop,
      dichlorprop, diclofop, fenoxaprop (herbicides) and for DF 1738Y, DF 1770Y, DF
      2008Y (drugs under evaluation). In order to optimize the chiral resolution we
      modified the polarity of the mobile phase by adding several polar additives such
      as ethyl acetate, dichloromethane, tert-butyl methyl ether. Better results were
      obtained for some herbicides on working with 2-propanol/CH2Cl2/n-hexane/acetic
      acid (8/4/87/1, v/v/v/v). The influence of the capillary temperature on chiral
      resolution was studied for two herbicides with different chemical structures,
      namely mecoprop and haloxyfop in the temperature range between 10 and 40 degrees
      C and with n-hexane/2-propanol/1% acetic acid (89/10/1, v/v/v) as the mobile
      phase. Linear correlation of ln k vs 1/T and In alpha vs 1/ T was observed;
      deltaH degrees values were negative, demonstrating that retention of analytes was
      an exothermic process. A decrease in resolution was observed with rising
      temperature, showing that enantioresolution was mainly influenced by selectivity
      factors.

PMID- 16894788
TI  - One-pot synthesis of polysaccharide 3,5-dimethylphenylcarbamates having a random
      vinyl group for immobilization on silica gel as chiral stationary phases.
AB  - Different kinds of vinyl groups were randomly introduced onto the glucose units
      of cellulose 3,5-dimethylphenylcarbamates by a one-pot method using the
      bifunctional reagents dec-1-ene-10-isocyanate, 2-isocyanatoethyl methacrylate,
      and methacryloyl chloride. The chiral recognition properties of the prepared
      derivatives were then evaluated by coating and immobilizing them on silica gel as
      HPLC packing material. Immobilization was carried out by radical copolymerization
      with a vinyl comonomer, 1,5-hexadiene, in toluene at 80 degrees C. The effects of
      the structures and content of the vinyl groups on the immobilization and on
      enantioseparations were investigated. This one-pot method was also extended to
      the synthesis of amylose 3,5-dimethylphenylcarbamates having a random vinyl
      group. Comparisons of the chiral resolution powers of our laboratory-made packing
      materials and the newly commercialized Chiralpak IA with immobilized amylose 3,5
      dimethylphenylcarbamate and Chiralpak IB with immobilized cellulose 3,5
      dimethylphenylcarbamate are discussed.

PMID- 16894789
TI  - Preparation and evaluation of a novel chiral stationary phase based on covalently
      bonded chitosan for ligand-exchange chromatography.
AB  - A novel chiral stationary phase based on chitosan covalently bonded onto silica
      gels has been prepared and used for the separation of various alpha-amino acid
      enantiomers as well as alpha-hydroxycarboxylic acid enantiomers by chiral ligand
      exchange chromatography with copper(II) as a complexing ion. The methanol content
      and copper(II) ion concentration in the eluent affected retentivity and
      enantioselectivity. Furthermore, a plausible chiral recognition mechanism for
      resolution of alpha-amino acids was proposed.

PMID- 16894791
TI  - A comparative evaluation of random and site-specific immobilization techniques
      for the preparation of antibody-based chiral stationary phases.
AB  - In this study, one random and four site-directed conjugation strategies were
      applied to immobilize an mAb, which stereoselectively binds to L-amino acids,
      onto silica particles. The resulting chiral stationary phases (CSPs) were used
      for enantiomer separation of the model-analyte D,L-phenylalanine and further
      examined in frontal affinity chromatography. Although random immobilization of
      the antibody onto discuccinimidyl carbonate-activated silica resulted in a CSP
      that enabled baseline separation of the enantiomers of D,L-phenylalanine, the
      amount of available binding sites was considerably lower compared to the CSPs
      prepared by site-directed strategies. Immobilization of antibody via its
      carbohydrate chains, either directly via hydrazone bonds between the support and
      the protein or indirectly via binding carbohydrate-biotinylated antibody to
      streptavidin-derivatized silica, resulted in medium column efficiencies. Higher
      amounts of available active sites were obtained by immobilizing the antibody
      indirectly through the "crystallizable fragment (Fc)" receptor protein A/G. The
      best results with regard to amount of available binding sites and column
      efficiency were obtained by first biotinylating the antibody specifically at its
      C-termini using carboxypeptidase Y and immobilizing the biotinylated antibody on
      streptavidin-derivatized silica.

PMID- 16894790
TI  - Chromatographic enantioseparation of amino acids using a new chiral stationary
      phase based on a macrocyclic glycopeptide antibiotic.
AB  - The separation of the enantiomers of several a-amino acids was studied on a new
      chiral stationary phase (CSP) which is based on the macrocyclic glycopeptide
      antibiotic eremomycin attached to silica particles. Retention and separation
      factors were determined under analytical conditions at ambient temperature for
      different mobile phase compositions. In order to evaluate the potential with
      respect to preparative separations the adsorption isotherms of D- and L
      methionine were determined for one mobile phase composition applying the elution
      by characteristic point method. The isotherms were validated by comparing
      experimentally determined elution profiles with predictions based on the
      equilibrium dispersive model. Finally, the performance of the eremomycin CSP was
      compared with a commercially available CSP based on the macrocyclic antibiotic
      teicoplanin. After determining the isotherms of D- and L-methionine also for the
      teicoplanin phase, the equilibrium dispersive model was used for both CSP to
      identify optimal operating conditions. For the separation and conditions
      considered the new eremomycin CSP revealed a better performance compared to the
      teicoplanin CSP.

PMID- 16894792
TI  - Fast chiral separation by ligand-exchange HPLC using a dynamically coated
      monolithic column.
AB  - The preparation and application of dynamically coated ligand-exchange
      chromatography phases for enantioseparation is described. The phases were
      prepared by pumping a solution of N-decyl-L-4-hydroxyproline, N-hexadecyl-L-4
      hydroxyproline, or N-2-hydroxydodecyl-L-4-hydroxyproline through a commercially
      available monolithic RP-18 column. These coatings are stable against desorption
      for months at ambient temperature when aqueous mobile phases are used. The
      columns were applied to the chiral separation of amino acids, glycyl dipeptides
      and diastereomeric dipeptides, and tripeptides. The chiral selector can be
      removed or changed easily by washing the column with ACN or methanol. Ultrafast
      separations in the range of seconds were achieved using high flow rates.

PMID- 16894793
TI  - Linear free energy relationship as a tool for characterization of three
      teicoplanin-based chiral stationary phases under various mobile phase
      compositions.
AB  - Teicoplanin, teicoplanin aglycon, and methylated teicoplanin aglycon chiral
      stationary phases (CSPs) have been compared on the basis of the regression
      coefficients calculated from the linear free energy relationship (LFER) equation.
      The parameters have been obtained from the measurements of a set of 34
      structurally diverse solutes. Influence of mobile phase composition - variation
      of methanol (MeOH) content - on the participation of different interactions types
      in the retention mechanism has been evaluated. Retention of the various
      interaction forces in analytes differs with both the CSP and the mobile phase
      composition. Hydrophobic interactions play a major role in mobile phases for high
      buffer contents. The more hydrophobic the CSP, the more important are they in the
      retention mechanism. With increase of MeOH contents in the mobile phase the major
      role in the interaction mechanism is shifted to more polar forces in which
      basicity and dipolarity/polarizability dominate. Although the LFER model does not
      address chiral aspects, we have attempted to explore the importance of the
      individual interactions in chiral discrimination of amino acids and their N-tert
      butyloxycarbonyl derivatives.

PMID- 16894794
TI  - Quinine carbamate chiral stationary phases: systematic optimization of steric
      selector-selectand binding increments and enantioselectivity by quantitative
      structure-enantioselectivity relationship studies.
AB  - A series of quinine carbamate-based chiral stationary phases (CSPs) differing
      solely in the carbamate residue have been devised and a congeneric set of N-3,5
      dinitrobenzoyl (DNB) amino acids (AAs) was separated into enantiomers on these
      CSPs by HPLC using a buffered hydro-organic mobile phase. Some details on
      retention and chiral recognition mechanisms have been investigated by application
      of quantitative structure-property relationship (QSPR) studies using the linear
      free energy relationship methodology, i.e., the extrathermodynamic approach.
      Retention factors of the high affinity enantiomer (log k2) and
      enantioselectivities (log alpha) were correlated with Taft's steric parameter as
      structural descriptor for the variability in the carbamate and AA residues, and
      statistically significant QSPR models could be obtained. They confirmed that the
      variance in the dependent variable (log k2, log alpha) is mainly associated with
      the steric bulkiness of the selectors' carbamate and of the AA residues. The
      retention factor of the second eluted enantiomers and the enantioselectivity
      first increased with steric bulkiness of the carbamate and AA residues, which may
      be explained by stronger dispersive interactions. After reaching an optimum, the
      dependent variable, however, declined with further increase of the steric
      bulkiness of the substituents, probably because of steric hindrance. The
      variability of the retention factors of the first eluted enantiomer could not be
      explained by steric descriptors. Instead, it has become obvious that the
      retention arises mainly from interactions of the DNB-AA and the quinine carbamate
      backbone, as it turned out to be more or less constant and solely to a minute
      amount modulated by the carbamate residue and the AA side chain. The QSPR models
      were fully in agreement with an earlier postulated chromatographically and
      spectroscopically derived hypothetical selector-selectand binding model.

PMID- 16894795
TI  - Gas chromatographic determination of the interconversion energy barrier for
      dimethyl-2,3-pentadienedioate enantiomers.
AB  - The enantiomers of dimethyl-2,3-pentadienedioate undergo interconversion during
      gas chromatographic separation on 2,6-di-O-methyl-3-O-pentyl-beta-, 2,6-di-O
      methyl-3-O-pentyl-gamma-, and 2,3-di-O-methyl-6-O-tert butyldimethylsilyl-beta-CD
      chiral stationary phases. The combination of a deconvolution method with an
      internal standard was used to determine individual enantiomer peak areas and
      retention times needed for the calculation of the interconversion rate constants
      and the energy barrier for dimethyl-2,3-pentadienedioate enantiomers. The kinetic
      and thermodynamic data obtained for the interconversion data (rate constants,
      energy barriers, enthalpies, and entropies) were in good agreement with the
      published data (Trapp, O., Schurig, V., Chirality 2002, 14, 465-470) using
      permethylated-beta-CD (Chirasil-beta-Dex).

PMID- 16894797
TI  - Use of evaporative light scattering detector in the detection and quantification
      of enantiomeric mixtures by HPLC.
AB  - Routinely used in our laboratories at analytical scale, an evaporative light
      scattering detector (ELSD) has proved to be versatile in the detection of
      enantiomeric resolution using chiral stationary phases by HPLC. Though this kind
      of detector has been widely used in various domains, its application in
      enantiomeric resolution has not been discussed in the literature and is found to
      have very specific features especially in the quantitative perspective. In
      contrast with the UV detection, the peak area from ELSD for both enantiomers of a
      racemic mixture may not be the same. This complicates the assessment of the
      enantiomeric purity of unknown samples. This current work deals with some
      practical aspects in the detection of enantiomers and in accurate quantitative
      determination of enantiomeric purity by ELSD. Effects of analyte nature (more
      precisely molecular weight and volatility), peak shape and peak shape difference
      between enantiomers on the quantitative integration by ELSD are discussed in
      connection with the UV-detection results. The calibration for quantitative
      enantiomeric analysis and its effectiveness are demonstrated.

PMID- 16894796
TI  - Dynamic HPLC on chiral stationary phases: a powerful tool for the investigation
      of stereomutation processes.
AB  - Dynamic HPLC on enantioselective stationary phases has become a well-established
      technique to investigate chiral molecules with internal motions that result in
      stereoinversion and occur on the time scale of the separation process. Kinetic
      parameters for the on-column interconversion phenomena can be extracted from
      experimental peak profiles by computer simulation or by direct calculation
      methods. The technique has been used in a wide range of temperatures and is
      complementary in scope to dynamic NMR spectroscopy.

PMID- 16894799
TI  - Effects of lower limb intensive mass practice in poststroke patients: single
      subject experimental design with long-term follow-up.
AB  - OBJECTIVE: To investigate the effects of two weeks of intensive mass practice
      with a constraint-induced movement therapy approach for the lower extremity in
      five chronic poststroke patients, and the persistence of effects at three and six
      months. DESIGN: A single-subject experimental design (SSED) was used with an AB
      design and follow-ups three and six months later. SETTING: Outpatient
      rehabilitation at Torsby Hospital in Sweden. MAIN MEASURES: Motor function in
      lower extremity, mobility, dynamic balance, weight-bearing symmetry and walking
      ability were measured on six occasions during two weeks (A phase), with the Fugl
      Meyer assessment for lower extremity, the Timed Up and Go, the Step Test, the
      Timed Walking Test and the Six-Minute Walk Test. During the intervention's B
      phase, six measurements were performed with the same time intervals as in the A
      phase. There were follow-ups three and six months later. INTERVENTION: The
      intervention (B phase) consisted of bicycling, training in water, strength
      training, standing weight-bearing, walking up and down stairs, walking indoors
      and outdoors and flexibility training of the lower extremity, on all weekdays, 6
      h a day for two weeks. RESULTS: The results showed improvements in 23/30
      variables (77%), 12 of them statistically significant (52%). At follow-up, 22/23
      improvements persisted. For example, three of five subjects walked significantly
      further after the intervention and the follow-ups showed that they still walked
      further than before the intervention. CONCLUSION: Intensive mass practice with
      constraint-induced movement therapy for the lower extremity can improve motor
      function, mobility, dynamic balance, weight-bearing symmetry and walking ability
      in chronic poststroke patients. Long-term follow-up showed that the effects
      persisted for these five subjects.

PMID- 16894798
TI  - Segmental stabilizing exercises and low back pain. What is the evidence? A
      systematic review of randomized controlled trials.
AB  - STUDY DESIGN: A systematic review of randomized controlled trials. OBJECTIVES: To
      evaluate the effectiveness of segmental stabilizing exercises for acute, subacute
      and chronic low back pain with regard to pain, recurrence of pain, disability and
      return to work. METHODS: MEDLINE, EMBASE, CINAHL, Cochrane Controlled Trials
      Register, PEDro and article reference lists were searched from 1988 onward.
      Randomized controlled trials with segmental stabilizing exercises for adult low
      back pain patients were included. Four comparisons were foreseen: (1)
      effectiveness of segmental stabilizing exercises versus treatment by general
      practitioner (GP); (2) effectiveness of segmental stabilizing exercises versus
      other physiotherapy treatment; (3) effectiveness of segmental stabilizing
      exercises combined with other physiotherapy treatment versus treatment by GP and
      (4) effectiveness of segmental stabilizing exercises combined with other
      physiotherapy treatment versus other physiotherapy treatment. RESULTS: Seven
      trials were included. For acute low back pain, segmental stabilizing exercises
      are equally effective in reducing short-term disability and pain and more
      effective in reducing long-term recurrence of low back pain than treatment by GP.
      For chronic low back pain, segmental stabilizing exercises are, in the short and
      long-term, more effective than GP treatment and may be as effective as other
      physiotherapy treatments in reducing disability and pain. There is limited
      evidence that segmental stabilizing exercises additional to other physiotherapy
      treatment are equally effective for pain and more effective concerning disability
      than other physiotherapy treatments alone. There is no evidence concerning
      subacute low back pain. CONCLUSION: For low back pain, segmental stabilizing
      exercises are more effective than treatment by GP but they are not more effective
      than other physiotherapy interventions.

PMID- 16894800
TI  - Long-term effects of the intensification of the transition between inpatient
      neurological rehabilitation and home care of stroke patients.
AB  - OBJECTIVE: To investigate an intensified transition concept between neurological
      inpatient rehabilitation and home care for long-term effects on the care
      situation two and a half years after stroke patients' discharge. DESIGN:
      Controlled clinical trial allocating patients to intervention group (intensified
      transition on ward II) or control group (standard transition on ward I); patients
      were allocated to whichever ward had a vacancy. The last follow-up assessment was
      carried out on average 31 months after discharge. INTERVENTION: The intensified
      transition concept consisted of therapeutic weekend care, bedside teaching and
      structured information for relatives during the second phase of the
      rehabilitation. SUBJECTS: Seventy-one patients and their family carers were
      included, of which one case dropped out. Therefore 70 family carers--35
      individuals in each group-- were available for assessment at long-term follow-up.
      DATA COLLECTION: Family carers were asked via telephone whether the patient was
      still alive and if so, where he or she is living--at home or in a nursing home.
      STATISTICAL METHODS: Binary logistic regression analysis with the care situation
      (home care versus institutionalized care or deceased) as dependent variable.
      RESULTS: Two and a half years after discharge (T3) in the intervention group
      significantly fewer patients were institutionalized (2 versus 5) or deceased (4
      versus 11) (P = 0.010). Multivariate analysis showed that besides a higher
      functional life quality at discharge and lower patient's age, the participation
      in the intensified transition programme is the third significant predictor for
      home care at T3. CONCLUSION: Effects of an intensified transition programme can
      persist over a long-term period. They can sustain home care by reducing
      institutionalization and mortality.

PMID- 16894801
TI  - Evaluation of the Swedish version of the Modified Elderly Mobility Scale (Swe M
      EMS) in patients with acute stroke.
AB  - OBJECTIVE: To investigate the inter-rater reliability and validity of the Swedish
      version of the Modified Elderly Mobility Scale (Swe M-EMS). DESIGN: A correlation
      study. SETTING: A stroke unit which provides acute care and rehabilitation for
      all stroke admissions in Northern Alvsborg County Hospital, Sweden. SUBJECTS:
      Thirty consecutive patients with an acute first-time stroke. Seventeen were women
      and 13 were men, with a median age of 79 years (41-92) and with a median hospital
      stay of 21 days (8-35). INTERVENTION: The patients were assessed twice with the
      Swe M-EMS on admission and at discharge, before and after midday, by two
      independent physiotherapists. They were assessed by an independent
      physiotherapist using the three evaluation instruments on admission, once a week
      during their hospital stay and at discharge. MAIN OUTCOME MEASURES: The primary
      evaluation instrument was the Swe M-EMS. The two other evaluation instruments
      were the Modified Motor Assessment Scale of Uppsala Akademiska Sjukhus-95 (M-MAS
      UAS-95) and the Berg Balance Scale (BBS). RESULTS: The Swe M-EMS was a reliable
      instrument (ICC 0.98-0.99). It correlated well with both the M-MAS UAS-95 (r(s) =
      0.69-0.88) and the BBS (r(s) = 0.86-0.94). The Swe M-EMS was sensitive to change
      over time, but the patients obtained the maximum score quickly. CONCLUSION: The
      instrument shows a high inter-rater reliability. The Swe M-EMS correlates well
      with both the M-MAS UAS-95 and the BBS and is sensitive to change. However, it is
      not sensitive enough to use as a single instrument in evaluating the improvement
      of a patient with acute stroke.

PMID- 16894802
TI  - An investigation into the utility of the Stroke Aphasic Depression Questionnaire
      (SADQ) in care home settings.
AB  - OBJECTIVE: To assess the utility of the Stroke Aphasia Depression Scale (SADQ) to
      identify emotional distress among individuals living in a care home setting.
      DESIGN: A prospective comparison of the SADQ and the depression subsection of the
      Hospital Anxiety and Depression Scale (HADS). SETTING: Care homes in Oxfordshire.
      PARTICIPANTS: Eighty-two care home residents without major communication or
      cognitive problems. MEASURES: Participants completed the HADS. The SADQ was
      completed on behalf of each resident by his or her principal carer. RESULTS:
      Spearman's rank correlation between the two measures was statistically
      significant (r = 0.447, P < 0.01). Receiver operator characteristics plots
      revealed an optimal cut-off point of 14 on the SADQ which gave sensitivity and
      specificity of 77% and 78% respectively. CONCLUSION: The SADQ, an observational
      measure, can identify emotional distress in non-aphasic patients in a care home
      setting. It would be reasonable to use it with people with communication and
      cognitive problems who are unable to take part in conventional assessments.

PMID- 16894803
TI  - The effect of lifting and lowering an external load on repositioning error of
      trunk flexion-extension in subjects with and without low back pain.
AB  - OBJECTIVE: To determine whether the repositioning error of trunk flexion
      extension in individuals with low back pain is different from that in those not
      experiencing low back pain when lifting and lowering external loads. DESIGN: A
      case-control study. SETTING: Physical therapy department of a medical centre.
      SUBJECTS: Twenty subjects with subacute low back pain and 20 control subjects
      without low back pain. INTERVENTIONS: Tasks with and without lifting and lowering
      an external load. MAIN OUTCOME MEASURES: The trunk repositioning errors were
      measured with Measurand Shape Tape. RESULTS: In subjects with low back pain,
      trunk repositioning errors were significantly reduced when lifting and lowering
      an external load in the direction of flexion (3.77 +/- 1.26 degrees in a loaded
      condition versus 4.82 +/- 2.97 degrees in an unloaded condition; P < 0.05) and
      extension (3.17 +/- 2.15 degrees in a loaded condition versus 5.03 +/- 3.74
      degrees in an unloaded condition; P < 0.05). In control subjects, trunk
      repositioning errors were not significantly changed when lifting and lowering an
      external load in the direction of flexion (2.80 +/- 1.39 degrees in a loaded
      condition versus 2.63 +/- 1.24 degrees in an unloaded condition; P > 0.05) and
      extension (2.87 +/- 11.40 degrees in a loaded condition versus 3.15 +/- 11.50
      degrees in an unloaded condition; P > 0.05). The direction of motion (trunk
      flexion or extension) was not shown to be significant in this study. CONCLUSION:
      Performing the task whilst lifting or lowering a submaximal load showed a reduced
      trunk repositioning error in subjects with subacute low back pain. Lifting and
      lowering a submaximal load might be considered as one of the rehabilitative
      strategies to hasten a return to work.

PMID- 16894804
TI  - The use of standardized outcome measures in rehabilitation centres in the UK.
AB  - AIM: To identify the standardized outcome measures currently used in routine
      clinical practice in rehabilitation centres in the UK. DESIGN: Cross-sectional
      survey by postal questionnaire. PARTICIPANTS: All UK consultant members of the
      British Society of Rehabilitation Medicine (BSRM) (n = 180). RESULTS: A total of
      108 (60%) responses were received, representing 83 different rehabilitation
      services. Of these, 71 (86%) collected at least one standardized measure. The
      Barthel Index and the UK Functional Independence Measure and/or Functional
      Assessment Measure (FIM +/- FAM) were the most popular global outcome measures:
      83% of units measured one or other of these. The Northwick Park Dependency Scale
      (NPDS) and Care Needs Assessment (NPCNA) (n = 21, 28%) were used for the more
      dependent patients. Depression and pain scores were more commonly used than
      general health measures. Sixty (72%) units routinely assessed outcome through the
      achievement of set goals, but only four transformed data to a goal attainment
      scale. Outcome measure scores were routinely reported in discharge summaries by
      72% of units. CONCLUSIONS: The survey demonstrated quite widespread use of
      outcome assessments in routine clinical rehabilitation within the UK, with an
      encouraging level of common measurement in some areas of practice. The results
      have been used to update the BSRM 'basket of recommended measures'.

PMID- 16894805
TI  - Sensitivity of a computer adaptive assessment for measuring functional mobility
      changes in children enrolled in a community fitness programme.
AB  - OBJECTIVE: To examine the relative sensitivity to detect functional mobility
      changes with a full-length parent questionnaire compared with a computerized
      adaptive testing version of the questionnaire after a 16-week group fitness
      programme. DESIGN: Prospective, pre- and posttest study with a 16-week group
      fitness intervention. SETTING: Three community-based fitness centres. SUBJECTS:
      Convenience sample of children (n = 28) with physical or developmental
      disabilities. INTERVENTIONS: A 16-week group exercise programme held twice a week
      in a community setting. MAIN MEASURES: A full-length (161 items) paper version of
      a mobility parent questionnaire based on the Pediatric Evaluation of Disability
      Inventory, but expanded to include expected skills of children up to 15 years old
      was compared with a 15-item computer adaptive testing version. Both measures were
      administered at pre- and posttest intervals. RESULTS: Both the full-length
      Pediatric Evaluation of Disability Inventory and the 15-item computer adaptive
      testing version detected significant changes between pre- and posttest scores,
      had large effect sizes, and standardized response means, with a modest decrease
      in the computer adaptive test as compared with the 161-item paper version.
      Correlations between the computer adaptive and paper formats across pre- and
      posttest scores ranged from r = 0.76 to 0.86. CONCLUSIONS: Both functional
      mobility test versions were able to detect positive functional changes at the end
      of the intervention period. Greater variability in score estimates was generated
      by the computerized adaptive testing version, which led to a relative reduction
      in sensitivity as defined by the standardized response mean. Extreme scores were
      generally more difficult for the computer adaptive format to estimate with as
      much accuracy as scores in the mid-range of the scale. However, the reduction in
      accuracy and sensitivity, which did not influence the group effect results in
      this study, is counterbalanced by the large reduction in testing burden.

PMID- 16894807
TI  - The adjective 'physical' in the term 'physical rehabilitation'.

PMID- 16894806
TI  - Assessment of unilateral spatial neglect post stroke in Canadian acute care
      hospitals: are we neglecting neglect?
AB  - OBJECTIVE: To estimate the prevalence, timing and frequency of use of
      standardized and non-standardized assessments to detect unilateral spatial
      neglect in acute care patients post stroke. DESIGN AND SETTING: Multicentred,
      retrospective study on medical charts from 10 randomly selected acute care
      hospitals in Ontario, Canada. SUBJECTS: Three hundred and twenty-four randomly
      selected medical charts of adult subjects with a primary diagnosis of stroke
      admitted in 2002 to the participating acute care hospitals. RESULTS: Out of 248
      subjects who should have been assessed, 38% received some form of unilateral
      spatial neglect assessment. Only 13% were assessed with a standardized assessment
      and of these, 4% within 48 h post stroke or within 48 h of the patient regaining
      consciousness as recommended by clinical practice guidelines for stroke.
      Bivariate analysis found significant associations between severity of cognitive
      impairment and being ever assessed, as well as between the severity of motor
      deficits of the upper extremity and being ever assessed. CONCLUSION: Routine
      standardized assessment of unilateral spatial neglect during the acute care phase
      post stroke was not incorporated into daily practice in this study sample.

PMID- 16894808
TI  - The pathocenosis moment: Mirko Grmek, the Annales and the vagaries of the longue
      duree.
AB  - Grmek's important article on pathocenosis, which appeared in 1969 in the Annales,
      did not achieve the fame and significance which it seemed to merit. This needs to
      be explained not only in terms of Grmek's own history, but also in changes in
      intellectual fashion, including in the Annales themselves. The work was also
      eclipsed by W.H. McNeill's best-selling Plagues and Peoples. History's 'cultural
      turn' since the 1980s has also limited the article's perceived utility.
      Nevertheless, the value of the concept is underlined by the articles in this
      collection.

PMID- 16894809
TI  - The dialectics of understanding: on genres and the use of debate in medical
      history.
AB  - Answering the call made by Frederic L. Holmes to introduce the concept of the
      longue duree in the history of science and medicine, this essay sets out to weigh
      the pros and cons of the concept for the field. It argues that four genres (or
      traditions) can be distinguished in medical historiography, each with their own
      ambitions, methods, perspectives and audiences. It concludes by calling for
      articulated and lively debate between the protagonists of the different genres as
      the royal way to historical understanding.

PMID- 16894810
TI  - History of disease and the longue duree.
AB  - This paper summarizes Grmek's theoretical contribution to history of disease and
      explores to what extent the longue duree could still be a useful concept in order
      to better understand past perceptions of, and reactions to, diseases. The case of
      the medical responses to epidemic disease in pre-industrial Europe is
      synthetically expounded in order to illustrate this issue.

PMID- 16894811
TI  - The galenic plague: a breakdown of the imperial pathocoenosis. Pathocoenosis and
      longue duree.
AB  - Is 'pathocoenosis', a notion conceived and a word coined by Mirko Grmek (1969),
      useful as far as ancient history is concerned? The author is interested in
      Galenic pathocoenosis, that of doctor Galen and his Emperor Marcus Aurelius (IInd
      cent. A.D.), when a new 'pestilence' or 'plague' (smallpox?) devastated the whole
      empire, from Mesopotamia to the Danube at least.

PMID- 16894812
TI  - The longue duree of contraceptive methods.
AB  - Medical history has so far paid hardly any attention to the longue duree, a
      history in which, according to Braudel, 'all change is slow'. It is therefore one
      of the challenges of the emerging field of the social history of medicine to work
      audaciously across time as well as across space. An interesting subject, for
      example, is the history of contraception. Throughout history, there has been
      almost nothing people have worried about more than having sex without fear of
      consequence. At first sight, the story of contraception seems to be one of
      progress, from the Ancient Egyptian crocodile-dung pessary to the modern-day
      condom and contraceptive pill. A closer look, however, shows a pattern of
      remarkable continuities in the reproductive behaviour of men and women over the
      last two thousand years. In this paper, I shall attempt to show why traditional
      male-dominated contraceptive methods still linger on despite the sexual
      revolution brought about by the invention of the 'pill' in the late 1950s.

PMID- 16894813
TI  - Medical miracles and the longue duree.
AB  - The hematologist-historian author became interested in the nature 'medical
      miracles', following a request to write a report on a set of bone marrows that
      was sent to the Vatican as a possible miracle cure in a cause for canonization.
      She questioned the prevalence of medical miracles, their structure, and
      relationship to other 'official' miracles that are recognized by the Church.
      Evidence was drawn from a variety of sources: oral testimony of pilgrims at feast
      day celebrations, ex voto paintings, and 160 miracle files in 67 canonization
      records of the Vatican Archives. Some changes can be detected through time, but
      the results also testify to remarkable longue duree in the healing experience:
      the patterns of suffering and despair, the gestures of pleading, the presence of
      beds and dreams, the astonishment of the caregivers, and above all the
      simultaneous recourse to medicine and religion both.

PMID- 16894815
TI  - Development of soil-covered SBR process for small scale sewage treatment.
AB  - Nitrogen and phosphorus compounds, mainly from the households in residential
      areas are responsible for eutrophication occurring in lakes or estuaries. In
      Korea, there is a growing trend for villages in the countryside, rest areas of
      express ways, military unit bases, etc. to use small scale sewage treatment
      plants (SSTPs). However, the technological developments have mainly focused on
      medium or large scale sewage treatment plants, leaving a gap in the development
      of technologies for SSTPs without a residing operator. In this study, a soil
      covered sequencing batch reactor (SBR) process for SSTPs in combination with a
      natural purification technology is developed to remove nitrogen and phosphorus as
      well as organic contamination (BOD), and the results are as follows: (1) the
      removal rates of BOD, total nitrogen (T-N), total phosphorus (T-P) and suspended
      solids (SS) are 93%, 74%, 80% and 95%, respectively, (2) the soil-covered SBR
      process without the decanter used for effluent discharge is similar to other SBR
      processes in suspended solids removal rate, and (3) the performance of the field
      pilot plant was monitored by remote sensing system in real time, and the results
      show that this system can be applied to SSTPs with no residing operators.

PMID- 16894814
TI  - Heterogeneous decomposition of indoor ammonia in a photoreactor with TiO2
      finished cotton fabrics.
AB  - Addition of urea-based antifreeze admixtures during cement mixing can make it
      possible to concrete cement in construction of buildings in cold weather. This,
      however has led to increasing indoor air pollution due to continuous
      transformation and emission from urea to gaseous ammonia in indoor concrete
      walls. In order to control ammonia from indoor concrete walls, aqueous dispersion
      of nano-titanium dioxide (TiO2) was prepared and mixed with silicone additive to
      establish a treating bath. Cotton fabrics were finished with this treating bath
      by using pad-dry-cure process and then characterized by X-Ray Diffractometer,
      Infrared Fourier Transform Spectrometer and Scanning Electron Microscope. The
      gaseous ammonia was derived from an environmental condition simulated chamber.
      The heterogeneous decomposition of gaseous ammonia by UV/TiO2 process in an
      annular photoreactor fixed with the TiO2-coated cotton fabric was studied under
      various dosages of aqueous nano-TiO2 dispersion, initial ammonia concentration,
      relative humidity and gas flow rate. A design equation of surface catalytic
      kinetics was developed for describing the decomposition of ammonia in air streams
      by UV/TiO2 process at given operating conditions. Experimental results indicated
      that increasing dosage of aqueous nano-TiO2 dispersion improved the ammonia
      decomposition of cotton fabric, which was prepared. At a constant temperature of
      25 degrees C, ammonia in the air stream was effective removed by decreasing
      initial ammonia concentration and gas flow rate. For moisture in the range of 15
      65%, when the relatively humidity level was increased to 45%, the decomposition
      of ammonia was remarkably enhanced, and the decomposition of ammonia could be
      inhibited by excessive moisture.

PMID- 16894816
TI  - Rheology of sludge in a complete retention membrane bioreactor.
AB  - A rheological characterization of the sludge sampled from a complete retention
      membrane bioreactor was performed in order to correlate the apparent viscosity
      with the concentration of solids. The three most commonly adopted models were
      tested to select the one better fitting the experimental data. Ostwald model was
      choosen, and the relationship between the apparent viscosity and the shear rate
      was determined for mixed liquor suspended solids (MLSS) concentrations ranging
      between 9 and 25 g l(-1). Ostwald model parameters k and n were correlated with
      MLSS concentration, comparing linear, power, and exponential-power (only for k)
      laws in terms of R2 and Mean Root Square Error (MRSE). Both power and exponential
      power functions provided good and comparable correlations for parameter k, while
      the linear relationship was much less accurate, especially at the highest solid
      concentrations. The parameter n was better modelled by a power function than by a
      linear one. Therefore two simulation models were proposed, both based on
      Ostwald's equation, where the two parameters k and n were expressed as functions
      of MLSS. Evaluation of energy consumption for mixing showed that the increase of
      solid concentration from 3 to 30 g l(-1) resulted in a limited increase in energy
      requirement (25-30 %). In real systems, where Reynolds numbers shift towards the
      turbulent regime, the increase of energy requirements for increasing solids
      concentration is even less pronounced. The thixotropy of membrane bioreactor
      sludge was also evaluated by measuring the rHa (reduced hysteresis area) and
      relating this parameter to the characteristics of the sludge growing within the
      reactor.

PMID- 16894817
TI  - Process improvement and energy saving in a full scale wastewater treatment plant:
      air supply regulation by a fuzzy logic system.
AB  - Achieving good performance in air supply control is an important goal in the
      management of wastewater treatment plants, whose highly nonlinear behaviour makes
      the application of conventional control techniques problematic. This paper
      presents the development and experimentation of a fuzzy logic system for air
      supply regulation in a full scale municipal wastewater treatment plant. The
      system is composed of two main modules, one devoted to continuously adjusting the
      DO set point on the basis of the current effluent NH4(+)-N concentration (on-line
      measurement), and the other devoted to achieve the DO set point by controlling
      air supply devices. The experiment was carried out on the plant for about one
      year, leading to significant advantages in terms of both process stability and
      energy saving.

PMID- 16894818
TI  - Photocatalytic degradation of water-soluble organic pollutants on TiO2 modified
      with gold nanoparticles.
AB  - Well characterised novel catalysts consisting of TiO2 modified with very small
      amounts of gold nanoparticles have been applied to the photocatalytic degradation
      of two important pollutants, methyl tert-butyl ether (MTBE) and 4-chlorophenol,
      in dilute aqueous solution using a fixed bed flow-through photocatalytic reactor.
      Although the thermal processing that was necessary for coating the reactor walls
      with the photocatalysts did lead to some loss of performance, the net gains in
      activity relative to unmodified TiO2 were nevertheless substantial and in excess
      of anything previously reported. Improvements in reaction rate by 50% and 100%
      for the removal of 4-chlorophenol and MTBE, respectively, were achieved. It was
      also found that effective removal of both pollutants could be achieved at water
      flow rates that are relevant to field applications involving the photocatalytic
      clean-up of contaminated groundwater. Due to their very small Au content, the
      cost of these materials is compatible with large scale use.

PMID- 16894819
TI  - Constructed wetlands and waste stabilization ponds for small rural communities in
      the United Kingdom: a comparison of land area requirements, performance and
      costs.
AB  - Land area requirements for secondary subsurface horizontal-flow constructed
      wetlands (CW) and primary and secondary facultative ponds with either unaerated
      or aerated rock filters were determined for three levels of effluent quality:
      that specified in the Urban Waste Water Treatment Directive (UWWTD) (< or = 25 mg
      filtered BOD l(-1) and < or = 150 mg SS l(-1) for waste stabilization ponds (WSP)
      effluents, and < or = 25 mg unfiltered BOD l(-1) for CW effluents (mean values);
      and two common requirements of the Environment Agency: < or = 40 mg BOD l(-1) and
      < or = 60 mg SS l(-1), and < or = 10 mg BOD l(-1), < or = 15 mg SS l(-1) and < or
      = 5 mg ammonia-N l(-1) (95-percentile values). A secondary CW requires 60 percent
      more land than a secondary facultative pond to produce an UWWTD-quality effluent,
      38 percent more land than a secondary facultative pond and an unaerated rock
      filter to produce a 40/60 effluent and, were it to be used to produce a 10/15/5
      effluent, it would require approximately 480 percent more land than a secondary
      facultative pond and an aerated rock filter. Its estimated 2005 cost is pound
      1100-2600 p.e.(-1), whereas that of a primary facultative pond and rock filter is
      approximately pound 400 p.e.(-1). On the basis of land area requirements,
      performance and cost, facultative ponds and unaerated or aerated rock filters are
      to be preferred to secondary subsurface horizontal-flow constructed wetlands.

PMID- 16894820
TI  - Removal efficiency of high-concentration H2S in a pilot-scale biotrickling
      filter.
AB  - A pilot-scale biotrickling filter (BTF) packed with polyurethane (PU) foam was
      installed at one pharmaceutical factory in Zhejiang Province to study the removal
      of high-concentration H2S from water treatment plant. Experiments were performed
      at different empty bed residence times (EBRTs), H2S input load, ratio of liquid
      flow rate to gas inlet rate (L/G) and sulfate concentration in recirculating
      liquid to examine their effects on the performance of the BTF. The performance of
      this bioreactor was monitored continuously over a period of 56 days. After the
      start-up within 8 days, H2S removal efficiency remained between 90% and 100% with
      inlet concentration fluctuating from 238 to 590 mg m(-3). H2S removal efficiency
      was consistently greater than 90%, even at a short EBRT of 9 s and inlet H2S load
      higher than 187 g m(-3) h(-1). Profiles over the height of the reactor indicated
      that H2S removal took place mostly in the first section of the column. The
      performance of BTF could be maintained at high and stable levels when L/G was
      below 0.005 and sulfate concentration down to 28 g l(-1). The results led to the
      conclusion that BTF is the optimal choice for treating high-concentration H2S.

PMID- 16894821
TI  - Effects of electrokinetics and cationic surfactant cetyltrimethylammonium bromide
      [CTAB] on the hydrocarbon removal and retention from contaminated soils.
AB  - Hydrocarbon contaminated soil and groundwater is considered to be a leading cause
      for increased health risk and environmental contamination. Therefore, an
      efficient technique is needed to retard the movement or enhance the removal of
      the contaminant depending on the remediation objective. The goals of this study
      were to evaluate the impact of the addition of a cationic surfactant on the
      movement of hydrocarbons within a contaminated clay soil subjected to
      electrokinetic treatment. Water-flushing and surfactant-flushing experiments were
      conducted on one-dimensional soil columns. The model diesel fuel was composed of
      a mixture of benzene, toluene, ethylbenzene, xylenes [BTEX] and three selected
      polycyclic hydrocarbons [PAHs]. In the water-flushing experiments, the
      application of an electrokinetic treatment was found to enhance the removal of
      PAHs from the clay columns by about 20%. In contrast, the application of an
      electrokinetic treatment, when coupled with cationic surfactant-flushing,
      retarded the movement of BTEX and the three selected PAHs in the clay columns.
      Hydraulic columns with surfactant (CTAB) removed 17% more naphthalene and 11%
      more 2-methylnaphthalene compared to columns subjected to electrokinetic
      treatment with CTAB. The flux through the electrokinetic columns during water
      flushing as well as surfactant flushing was higher than the flux due to hydraulic
      gradient alone. As the solubility of hydrocarbons increased, they moved farther
      with electrokinetic treatment without CTAB. However, with CTAB the electrokinetic
      treatment tends to retard the movement. Use of a cationic surfactant coupled with
      electrokinetic treatment was found to retard the movement of contaminants.

PMID- 16894822
TI  - Backwash based methodology for the estimation of solids retention time in
      biological aerated filter.
AB  - The concept of solids retention time (SRT) was used for describing the growth of
      biofilm in a biological aerated filter (BAF) system. The SRT profile was obtained
      from the change in solids accumulation, estimated from the head loss profile data
      before and after backwash using the Carmen-Kozeny equation. The SRT profile along
      the filter bed depth showed the SRT of about 2 days for the lower layer and about
      6 days for the upper layer. The overall SRT was determined by the direct
      estimation of excess solids mass during backwash and of solids retained in the
      filter bed. The ideal characteristic SRT distribution was maintained by regular
      backwash, for organic removal and nitrification. The SRT for high organic removal
      and nitrification is demonstrated by the SRT distribution along the filter bed in
      this BAF process.

PMID- 16894823
TI  - Ultraviolet spectrophotometry as an index parameter for estimating the
      biochemical oxygen demand of domestic wastewater.
AB  - The relationship between ultraviolet absorbance at 280 nm (UV280) and the 5-day
      Biochemical Oxygen Demand (BOD5) test was evaluated using wastewater samples
      collected during March - December 1998 from the Fort Meade wastewater treatment
      plant (Maryland, U.S.A.). Three types of samples were collected: raw influent
      wastewater, primary effluent, and the effluent from the nitrification settling
      basin. A regression of BOD5 on UV280 was obtained using half of the data, with
      the other half of the data used to test application of the equation. The presence
      of NO3 and NO2, did not interfere with the BOD5/UV relationship. However, the
      relative fraction of organic compounds that absorb at UV280 and are biodegradable
      did appear to decrease across the treatment plant, thereby reducing the strength
      of the association between BOD5 and UV280 further along the treatment train.
      Interestingly, the exclusion of solids > 1 microm from the BOD5 test did not
      strengthen the association between BOD5 and UV280. These results suggest that
      simple UV absorbance measurements may be a useful analytical tool for wastewater
      treatment personnel, allowing them to quickly monitor for changes in the BOD5
      during the treatment process and to quickly estimate the BOD5 when determining
      what dilutions to use in the standard BOD5 test. However, such relationships are
      likely to be wastewater and treatment plant specific and variable with time and
      treatment.

PMID- 16894824
TI  - Wollastonite as reactive filter medium for sorption of wastewater ammonium and
      phosphorus.
AB  - The utilisation of reactive filter media to remove ammonium and phosphorus can
      improve the effluent water quality of wastewater treatment systems. The objective
      of this study was to estimate the ammonium and phosphorus sorption capacity of
      wollastonite, a calcium meta silicate (CaSiO3) that is distributed worldwide.
      Phosphorus sorption mechanisms were also investigated. Batch sorption experiments
      with agitating bottles were carried out and both phosphate and ammonium solutions
      as well as wastewater were used. The results showed minor ammonium adsorption,
      with only 3-15% of the ammonium in the solutions being adsorbed to the
      wollastonite. Neither the reaction time (0.5-20 h) nor the initial concentrations
      of phosphorus and ammonium (11-114 mg l(-1) NH4-N) were of importance. For high
      initial phosphate concentrations, phosphate was greatly sorbed to the
      wollastonite (850 mg kg(-1) at an initial phosphate concentration of 61 mg l(-1)
      PO4-P). However, phosphate sorption was minor when the initial phosphate
      concentration was low. This study showed that sorption reactions were important
      when phosphate was removed by wollastonite, and indicated precipitation of
      phosphate on the wollastonite surfaces as one possible mechanism for phosphate
      retention. The results from this study indicated that the wollastonite
      investigated may not be suitable for municipal wastewater treatment applications
      due to the low phosphorus sorption capacity for low initial phosphorus
      concentrations.

PMID- 16894825
TI  - Removal of multiple-metals from contaminated clay minerals.
AB  - Clay minerals spiked with multi-component metal ions (Cu(+2), Cd(+2), Pb(+2))
      were decontaminated using different soil washing solutions. The desorption
      characteristics were determined by batch acid leaching with various acids.
      Removal of Cu(2+), Cd(+2) and Pb(+2) ions from variable charge minerals (e.g.
      kaolinite) required much less effort than their removal from constant-charge
      minerals (e.g. illite). The surface charge of a clay mineral had an important
      influence. When the numbers of H+ and Na+ ions available in the soil were
      increased by adding a buffer solution such as NaOAc-HOAc, heavy metals adsorbed
      on the clay surface transferred to the pore fluid. When more H+ or Na+ ions were
      available in the pore fluid, more Cu(+2), Cd(+2) and Pb(+2) ions were released
      into the equilibrium solution. Decreasing the pH led to more removal of heavy
      metal ions from kaolinite. The presence of Na+ ions facilitated the removal of
      heavy metals from contaminated illite. The selectivity for desorption was in the
      order Cu(+2) > Cd(+2) > Pb(+2) for all washing solutions investigated.

PMID- 16894826
TI  - A program to reduce the disparity in the rate of biennial lipid profiles between
      African-American and white Medicare beneficiaries with diabetes mellitus in New
      York City.
AB  - The burden of diabetes is more severe for minority populations than for the white
      population in the United States. Analysis of Medicare fee-for-service claims data
      revealed a significant disparity regarding screening for lipids between white and
      African-American Medicare beneficiaries with diabetes as measured by the biennial
      lipid profile indicator in New York State and the disparity was even greater in
      New York City. Thus IPRO, the Medicare New York State Quality Improvement
      Organization, launched a multifaceted quality improvement project to reduce the
      disparity, targeting African-American Medicare beneficiaries with diabetes in New
      York City and the providers who serve them. There was an absolute increase of
      16.7% in the proportion of African-American beneficiaries with diabetes receiving
      a biennial lipid profile in the intervention areas and the disparity reduced by
      9.8% between African-American and all eligible white beneficiaries in the
      intervention areas. Although it was not feasible to determine the direct impact
      of selected interventions on reducing the disparity, the interventions
      collectively appeared to be effective.

PMID- 16894828
TI  - A comparison of nonfatal unintentional injuries in the United States among U.S.
      born and foreign-born persons.
AB  - The objective of this research was to compare the risk of nonfatal unintentional
      injuries between foreign-born and U.S.-born persons. Cross-sectional, nationally
      representative data were used from the 2000-2003 National Health Interview Survey
      to compare the risk of injury between 62,267 foreign-born and 322,200 U.S.-born
      persons. Nonfatal unintentional injuries occurring during the three months prior
      to the interview were compared by age, gender, education, poverty status, region
      of residence, family size, and health insurance coverage status. There were a
      total of 7,654 injured persons with U.S.-born persons having a weighted injury
      prevalence of 2.3% (95% confidence interval [CI]: 2.2, 2.4) and foreign-born
      persons having a weighted injury prevalence of 1.2% (95% CI: 1.0, 1.3). With the
      U.S.-born population as the reference and while controlling for sociodemographic
      characteristics, the odds ratio of injury risk was 0.54 (95% CI: 0.48, 0.62) for
      the foreign-born population. Transportation-related injuries occurred more
      frequently among foreign-born persons than among U.S.-born persons (23.7%, 95%
      CI: 19.7, 28.3 vs. 15.0%, 95% CI: 14.0, 16.2, respectively). This research is the
      first step in determining the morbidity from unintentional injuries among the
      foreign-born population in the U.S.

PMID- 16894829
TI  - Worksite and communications-based promotion of a local walking path.
AB  - Current research has shown relationships between the environment (eg, parks and
      trails) and levels of physical activity participation. This study was designed to
      implement and evaluate a communications based worksite campaign to promote
      awareness of an existing local walking path and to increase walking. Promotional
      materials were distributed for 1 month via flyers, email, website postings, and
      during bi-weekly information booths. Evaluations were conducted at baseline,
      during, and following the promotional campaign. Borderline statistically
      significant increases in walking activity from baseline were observed midway
      through the campaign (p = 0.069) and following the campaign (p = 0.075). Counts
      observed during the intervention were almost triple those at baseline and
      increased in the post-campaign phase to approximately three and a half times
      those at baseline. Sign recognition surveys revealed at baseline, 51% of the
      participants correctly identified the walking path signs, which increased to 65%
      during the campaign (p = .0674). Familiarity with physical activity messages
      around the workplace increased from 64.6% at baseline to 75.5% during the
      campaign (p = .097). This study shows initial promise of a theoretically based
      communications intervention to increase knowledge of physical activity and to
      promote walking.

PMID- 16894827
TI  - Living near a trail is associated with increased odds of walking among patients
      using community clinics.
AB  - We tested the hypothesis that living near a walking or cycling trail was
      associated with greater odds of walking. This has been previously studied in
      healthy and unselected populations, but to our knowledge has not been studied in
      patients attending community clinics. A cross-sectional survey was completed by
      1211 persons in five community clinics that serve poor populations. We performed
      univariate analysis and developed a multivariate logistic regression model for
      walking adjusting for 12 independent variables including self-rated health,
      frequent mental distress, lifestyle and demographic variables, and environmental
      characteristics of the neighborhood including perceived proximity to a walking or
      cycling trail. Compared to those who reported not living close to a trail,
      persons who reported living near a trail were more likely to meet recommended
      levels of walking of at least 30 minutes fives times per week (unadjusted odds
      ratio = 1.49, 95% confidence intervals = 1.04-2.13). In the multivariate model,
      male gender (unadjusted odds ratio = 1.63, 95% confidence intervals = 1.15-2.30),
      having three or more convenient destinations (unadjusted odds ratio = 1.78, 95%
      confidence intervals = 1.37-2.32), and living near a trail (unadjusted odds ratio
      = 1.45, 95% confidence intervals = 1.01-2.09) were positively associated with
      walking at statistically significant levels. The odds of walking were lower in
      non-Hispanic blacks (odds ratio = 0.59, 95% confidence intervals = 0.40-0.87) and
      current smokers (odds ratio = 0.66, 95% confidence intervals = 0.57-0.76). For
      patients attending community clinics, environmental strategies to encourage
      walking may include mixed-land-use neighborhoods and construction of trails.

PMID- 16894830
TI  - Participation and program outcomes in a church-based cancer prevention program
      for Hispanic women.
AB  - This study examined program attendance and related outcomes for Companeros en la
      Salud, a church-based culturally focused health promotion program specifically
      designed for low-acculturated, low-income Hispanic women. In this church-based
      study, the cancer prevention intervention was the major intervention group, and
      its effects were compared with a noncancer-oriented family mental health group.
      The goal of the present study was to identity predictors of program attendance
      and increases in cancer prevention knowledge and behaviors. Lower levels of
      acculturation level and greater overall church attendance were predictive of
      program attendance for Hispanic women in the cancer prevention component. Also,
      attendance in the cancer intervention component of the Companeros en la Salud
      program was predictive of posttest cancer prevention knowledge. By contrast,
      higher acculturation level was a significant predictor of having had a clinical
      breast exam at posttest. Similarly, younger age and lower fear of cancer were
      predictive of having had a pap smear at posttest. Finally, pretest cancer
      prevention knowledge was a significant predictor of mammography screening for
      women ages 40 and over. These results offer implications for the development of
      culturally tailored cancer prevention programs for Hispanic women.

PMID- 16894831
TI  - The new science of siblings.

PMID- 16894832
TI  - The perils of cloning.

PMID- 16894833
TI  - The first 50 years of the Papua New Guinea Medical Journal: a celebration of its
      golden jubilee.

PMID- 16894834
TI  - Some epidemiological features of pig-bel. 1966.

PMID- 16894835
TI  - The pathogenesis of pig-bel in Papua New Guinea. 1979.

PMID- 16894837
TI  - Strongyloides infection in a mid-mountain Papua New Guinea community: results of
      an epidemiological survey. 1979.

PMID- 16894836
TI  - Strongyloides species infestation in young infants of Papua New Guinea:
      association with generalized oedema. 1979.

PMID- 16894838
TI  - Weanling diarrhoea. 1971.

PMID- 16894839
TI  - The bacteriology of acute pneumonia and meningitis in children in Papua New
      Guinea: assumptions, facts and technical strategies. 1991.

PMID- 16894841
TI  - Small-area variations in the epidemiology of malaria in Madang Province. 1986.

PMID- 16894840
TI  - Nutrition and morbidity: acute lower respiratory tract infections, diarrhoea and
      malaria. 1988.

PMID- 16894842
TI  - Hereditary ovalocytosis in Melanesians. 1977.

PMID- 16894843
TI  - Trends in sexually transmitted disease incidence in Papua New Guinea. 1984.

PMID- 16894845
TI  - A productive partnership.

PMID- 16894844
TI  - A New Guinea population in which blood pressure appears to fall as age advances.
      1965.

PMID- 16894846
TI  - Rocky road ahead for children's health insurance law?

PMID- 16894847
TI  - Waivers permit states to better tailor Medicaid.

PMID- 16894848
TI  - States push back on the "clawback".

PMID- 16894849
TI  - Supreme court allows enforcement for health plans seeking reimbursement.
AB  - On May 15, the U.S. Supreme Court decided a key question in the struggle to keep
      health costs affordable: Can employer-based health insurance plans seek a portion
      of the proceeds when their members have recovered money by suing those
      responsible for injuries incurred as a result of auto collisions or other
      accidents? The court held unanimously in the affirmative, thus clarifying an
      issue that had been disputed among the federal circuit courts and allowing for
      uniform enforcement of reimbursement and subrogation provisions by health
      insurance plans.

PMID- 16894850
TI  - Navigating new terrain.

PMID- 16894851
TI  - Opening doors on disease management.

PMID- 16894852
TI  - A helping hand.
AB  - Medicaid beneficiaries can be a particularly challenging population to serve. Too
      often they experience exaggerated health problems that are exacerbated, in many
      instances, by a long history of being left behind by the health care system. They
      face an uphill battle getting to doctor's appointments because they lack
      transportation, or they have trouble negotiating the health delivery system
      because of limited knowledge about the process and their health conditions. At
      the same time, the Medicaid-eligible population continues to grow, straining
      state budgets. To help remove the barriers to care while keeping costs down,
      Medicaid program administrators have partnered with managed care plans. In
      response, Medicaid managed care plans have cultivated relationships with
      grassroots organizations to develop community-centric programs that more
      effectively reach out to this targeted population of mothers, underserved
      children and teens, individuals with chronic health conditions, and the
      culturally and linguistically diverse.

PMID- 16894853
TI  - Turning subscribers into customers: the future is now.
AB  - The launch of Medicare's prescription drug plan marks a major milestone in
      federal health policy. Nearly 90 percent of Medicare's 43 million beneficiaries
      now have some form of prescription drug coverage, approximately 6 million of whom
      had no coverage prior to the introduction of Part D. The enrollment boom presents
      a tremendous opportunity for health insurers. But the new enrollments also
      present a challenge, as insurers' ability to build customer loyalty will depend
      on their success in reorienting themselves to the consumer market where tastes
      can be even more fickle than in the group business. The good news is that as
      insurers focus on serving senior customers, there is an even more promising
      opportunity on the horizon than Medicare Part D: providing products that help
      consumers-particularly retirees and those nearing retirement-to plan for and
      manage their out-of-pocket health care spending. The retirement health market
      beyond Medicare Advantage and Part D could significantly impact many health
      insurers' bottom line; it's expected to generate $80 billion in revenues and $8
      $12 billion in pre-tax profits by 2014.

PMID- 16894854
TI  - Part D implementation: how did health plans fare? A conversation with Stan Nowak,
      founder, president, and chief executive officer of Silverlink Communications.
      Interview by William Atkinson.
AB  - Medicare part D is a large-scale example of a true consumer-directed health
      insurance plan. With Part D, 42 million Americans can select from any one of
      dozens of Medicare Advantage or stand-alone prescription plans available to them.
      At the end of each year, beneficiaries will be able to evaluate their
      satisfaction with their chosen plan, assess other available options and determine
      whether to re-enroll or choose a new plan. Consumers rule.

PMID- 16894856
TI  - A carrier that makes the grade. Conduct a performance review to find a reinsurer
      that meets your needs.
AB  - Remember report card day? As kids, some of us looked forward to-or dreaded
      handing our grades over to our parents more than others. In the same way that a
      report card gives parents an indication of how well their children are performing
      in school, a similar type of performance review can help HMO reinsurance
      purchasers evaluate and select a reinsurer.

PMID- 16894855
TI  - Surviving and thriving in the medicare part D market. Long-term partnerships can
      help health plans meet requirements.
AB  - The Medicare prescription drug, Improvement and Modernization Act of 2003 (MMA)
      is the largest push of government-funded health care into the private insurance
      market in Medicare's history. The Part D prescription drug benefit has garnered
      recent headlines due to the large number of seniors interested in-and a few
      confused by-the program. But if some seniors are flummoxed by Part D, many
      private insurers are equally perplexed by the complexities of marketing and
      administering these programs.

PMID- 16894857
TI  - Software license agreements: don't get locked into bad deals. Do's and don'ts of
      negotiating the best long-term arrangement with IT vendors.
AB  - Selecting, implementing and operating the right technology solutions are
      increasingly critical components for health plans in today's competitive consumer
      health care market. Decisions about what architecture to employ, what software
      applications to buy and what hardware platform to run affect a plan's ability to
      become a market leader. Additionally, health plans must consider the best
      approaches for maintaining and operating their IT solutions, which inevitably
      include employing a global sourcing strategy that extends IT budgets and
      expertise while lowering costs.

PMID- 16894858
TI  - The choking game or suffocation roulette in adolescence.

PMID- 16894859
TI  - Cyberchondriacs.
AB  - Over 110 million Americans have accessed the internet for healthcare information.
      This information is often used in medical consultations and possibly contributing
      to increasing health care burdens. Although well informed patients are an
      advantage in disease management, the quality and reliability of information
      online is variable. Adolescents today have grown up with the Internet as a
      primary knowledge source, but still lack the skills to effectively filter
      credible information. Voluntary standards on health information have been
      attempted by Health on the Net Foundation; however their success has been
      limited, mainly due to the fact that most people searching for health information
      on line use a search engine rather than a specific site. This makes regulations
      almost impossible. Cyberchondriacs, a term used to describe anyone who seeks
      health-related information on the Internet, are not only at risk of acquiring
      unreliable information on line and therefore potential unnecessary anxiety, but
      they could also be financially exploited, for example, by e-health organisations
      and pharmaceutical companies. Moreover, the vulnerable e-health seeker, such as
      the inexperienced adolescent, is able to buy any quantity of nearly any
      medication on-line. Reasons for patients seeking information on line are varied,
      but include not having enough time at consultations. To try to address these
      issues, organisations such as NHS direct have been set up but their success is
      difficult to measure due to a lack of data. However, potential exploitation of a
      vulnerable population and the motivations behind their search for information on
      the internet merit further study.

PMID- 16894860
TI  - Comparison of symptoms and treatments of adults and adolescents with borderline
      personality disorder.
AB  - The purpose of this paper was to characterize adolescent borderline personality
      disorder (BPD) and compare it to adult BPD. A retrospective chart review of 20
      adolescent and 20 adult BPD patients was conducted. The retrieved data included
      demographics, history features, symptoms, observations made during
      hospitalization and treatments. There were many similarities between the two
      groups. The differences included the number of report pages during
      hospitalization (p<0.05), of current self-mutilation (p=0.051), of past and
      present obsessive-compulsive symptoms (p=0.02 and p=0.03) and of past escapes
      (p=0.006). Adults had more alcohol abuse (p=0.02). There was a correlation
      between the number of anti-psychotic drug trials and the length of
      hospitalization among adolescents, and a correlation between the number of
      antidepressant and anxiolytic drug trials and the length of hospitalization among
      adults. Our findings support the general similarity of BPD between adolescents
      and adults. The differences in pharmacotherapy and several clinical observations
      warrant further study.

PMID- 16894861
TI  - Cannabis use and mood disorders: patterns of clinical presentations among
      adolescents in a developing country.
AB  - Notwithstanding the increase use of cannabis among adolescents in both developing
      and developed countries, few studies have looked at cannabis use and mood
      disorders. In a series of case studies, this research project seeks to
      investigate patterns of clinical presentations seen among cannabis users in
      psychiatric outpatients in Trinidad. Five clinical patterns of presentations are
      identified among cannabis users and abusers based on variables of dosing, age of
      initial use, duration of use, tolerance and reverse tolerance and poly-drug
      abuse. All patients in these case studies were standardized for method of use and
      potency of cannabis used. Patients were screened by urine tests to determine co
      morbid use of other substances. Other variables such as environmental factors and
      genetic vulnerability were reviewed as far as possible from historical accounts
      of family members. The five patterns described are low, controlled use with mild
      euphoria and heightened awareness, moderate use with mixed depressive symptoms
      and suicidal behaviour, heavy, short term use with manic symptoms, long term
      incremental use with psychotic symptoms due to the trumping of depressive
      symptoms and cannabis mixed with other substances resulting in florid psychosis.
      Mood disorders appear to be a common finding among adolescents using cannabis.
      Sensitization to symptomatic presentation and early detection of cannabis use in
      young adolescents are necessary. Further research is needed on the effect of
      cannabinoids on emotions, behaviour and thinking and its relationship to mental
      disorders. This study is useful as a guideline for the implementation of public
      health strategies and legislation concerning the use of cannabis in youths.

PMID- 16894862
TI  - Is perceived family dysfunction related to comorbid psychopathology? A study at
      an eating disorder day treatment program.
AB  - The role of the family in the development of eating disorders has been a
      predominant research focus. However, few studies of patients in an eating
      disorder (ED) day treatment program (DTP) have explored the relationship between
      self-reported family system functioning, self-reported comorbid psychopathology
      and current comorbid psychological symptom status. This study examined patients
      at presentation to an ED DTP, their self-reported perception of family
      functioning and the relationship with characteristics of their own comorbid
      psychopathology characteristics. Medical records of 51 day treatment female
      patients, ranging in age from 12 to 26 years, were examined by ED diagnosis and
      family type (using the FACES-II), and for significant differences on four self
      report measures: SCL-90, EDI-2, BDI and TAS-20. Using MANOVA analyses and
      Bonferroni comparisons, significant differences on the self-report instruments
      for the entire sample and for the AN and BN patients were obtained when studying
      patients within different family types as defined by FACES-II. These data
      specific to DTP patients support previous findings for both IP and OP ED family
      studies. Overall, as family functioning was perceived to be more dysfunctional,
      the level of self-reported eating pathology and current comorbid psychological
      symptoms was also more severe.

PMID- 16894863
TI  - A population-based study of 18-year old Swedish youths and factors correlated
      with their total number of lifetime sexual partners.
AB  - The number of sexual partners has in studies been shown to be a factor correlated
      with STI but there is little published knowledge on what factors are associated
      with number of sexual partners. OBJECTIVES: To examine which variables are
      correlated with the number of lifetime sexual partners (NLSP) among youths. STUDY
      GROUP: All 18-year old girls and boys in four cities in northern Sweden. METHODS:
      A population-based study where participants answered a questionnaire regarding
      their social lifestyle, psychological and sexual health. The associations between
      these independent variables and the dependent variable (NLSP) were investigated
      by multivariate linear regression analysis. RESULTS: The boy and girl median NLSP
      was 2.0 (P25 =1.0, P75=3.0). The final model explained 29% of the total boy NLSP
      variation and 46% of the total girl NLSP variation. Eight boy variables and
      thirteen girl variables significantly correlated with NLSP were found. The two
      strongest variables associated with increased NLSP among boys and girls, was
      feelings of guilt or shame after sex and smoking regularly. Variables prior
      associated with an increased risk of acquiring STI's were associated with
      increased NLSP. The study found new gender differed behaviour variables
      correlated to NLSP not previously considered to be risk factors for STI.
      CONCLUSIONS: To prevent the spread of STI it is important that persons with many
      partners are identified, treated if necessary and possible, or encouraged to
      change their behaviour. The study found several boy and girl variables associated
      with increased NLSP, which could facilitate both primary- and secondary
      preventions.

PMID- 16894864
TI  - Frequency, satisfaction and quality dimensions of perceived parent-adolescent
      communication among Chinese adolescents in Hong Kong.
AB  - Chinese adolescents (N=88) responded to instruments measuring three dimensions of
      parent-adolescent communication (frequency of parent-adolescent communication,
      satisfaction with parent-adolescent communication and quality of parent
      adolescent communication) and adolescent psychological well-being (mastery and
      life satisfaction). Results showed that Chinese adolescents perceived sharp
      distinction between fathers and mothers in terms of these three dimensions:
      fathers were perceived to have less communication with adolescents than did the
      mothers; the satisfaction and quality ratings for father-adolescent communication
      were lower than those based on mother-adolescent communication. Results also
      showed that relative to the frequency of parent-adolescent communication,
      satisfaction with and quality of parent-adolescent communication were more
      strongly related to adolescent psychological well-being. Although global quality
      of father-adolescent communication and mother-adolescent communication were
      related to adolescent life satisfaction, global quality of father-adolescent
      communication appeared to have a stronger relationship with adolescent mastery
      than did mother-adolescent communication.

PMID- 16894865
TI  - Situational runaway adolescents. A study on risk factors from a Turkish sample.
AB  - Drawing on a sample of 726 non-clinical adolescents (aged 17-18 years) from high
      schools in Ankara, Turkey, this paper primarily aims to identify the risk factors
      related to situational run away behavior. This study was based on an ecological
      risk factors model and tried to discover the associations for runaways. Run away
      behavior is one of the problematic behaviors very commonly seen among Turkish
      adolescents. Regression analyses revealed that predictors for runaway behavior
      differed due to gender; while, delinquency, sexual intercourse, substance use,
      parental separation and suicidal ideation were the significant predictors for
      girl adolescent runaway behaviors, while lack of parental support and depression
      were the significant predictors for boy adolescent runaway behavior.

PMID- 16894866
TI  - What may underlie differing perceptions of family functioning between mothers and
      their adolescent daughters with eating disorders?
AB  - Daughters with eating disorders (ED) were found to perceive family functioning
      more negatively than their mothers. This study examined variables that may
      underlie these differences in a subgroup of adolescent girls and their mothers
      from the original study. METHODS: Participants were 77 mother-adolescent daughter
      dyads. Daughters met current DSM-IV criteria for Anorexia Nervosa, Bulimia
      Nervosa or ED Not Otherwise Specified. Daughters and mothers completed the Family
      Assessment Device (FAD), which measures perceptions of family functioning with
      seven subscales. Daughters also completed the Eating Disorders Inventory (EDI).
      Backward elimination stepwise regressions were conducted on difference scores
      between mothers and daughters for each FAD subscale. Daughter's EDI subscales
      (except Bulimia) were entered as possible predictors. RESULTS: Interpersonal
      Distrust was the only predictor of the differences between daughters and mothers
      on Problem Solving, Communication, Affective Responsiveness and General
      Functioning, accounting for 24%, 14%, 10% and 23% of the variance, respectively.
      CONCLUSIONS: Differences in viewpoints between mothers and daughters regarding
      the family environment may be understood in terms of the daughters' level of
      distrust of people in general and their overall feelings of inadequacy.
      Addressing these psychological difficulties may have powerful implications both
      for individual and family treatment in the recovery from an eating disorder.
      Could this be part of the dynamic that led to the eating disorder, a result of
      the stress on the whole family related to the eating disorder or some
      combination?

PMID- 16894868
TI  - [The Activity Theory as a conceptual model for nursing].
AB  - The search for theoretical models in order to provide inputs and to reconsider
      the nursing practice, as well as to found research and teaching, has been a
      concern among contemporaneous nursing researchers. This article proposes a glance
      at the pedagogical assumption that supports the application of the Activity
      Theory, i.e., qualifying subjects to learn how to learn, to build and to search
      for knowledge. This theory also assumes actions in dynamic contexts of action
      operation, a feature that must be emphasized in nursing education, as well as in
      the development of the abilities needed for group work.

PMID- 16894867
TI  - Gender differences in the factors influencing consistent condom use among young
      people in Tanzania.
AB  - AIDS has become a major cause of death in Tanzania and young people represent the
      most vulnerable group. Recent HIV prevalence data showed that young women are
      more likely than young men to become infected. This paper examined commonalties
      and differences in the sociodemographic and ideational predictors of condom use
      among young men and women in Tanzania. The data derive from a 2004 sample survey
      among young people aged 15-24 years in five regions of Tanzania. The sample on
      which the analyses were based included 1,523 single women and 1,200 single men.
      An ideation framework guided the analyses of the predictors of consistent condom
      use. Logistic regression was the main analytic method used and separate models
      were estimated for men and women. The most significant correlates of consistent
      condom use for men included perceived self-efficacy for correct condom use,
      discussing condom use with friends, and perceived self-efficacy for using condoms
      with a long-term partner. Discussing condom use with a sex partner and the
      perceived self-efficacy to refuse sex if the sex partner refused to use a condom
      were the most significant predictors for women. One implication of the findings
      is that for men, effective interventions should emphasize correct condom use know
      how and address the issue of negative peer pressure and group norms around condom
      use. For women, interventions should focus on sexual empowerment.

PMID- 16894869
TI  - [The lay midwife care to woman upon delivery and her childbirth].
AB  - It is a research aimed at finding out the lay midwives' practices while attending
      women upon delivery and their childbirth. The methodology was supported by the
      oral history of the midwives, using Bardin's thematic analysis. The findings
      regarding the midwives' activities reveal the domestic character of their
      practices, being themselves one of these resources, besides others that they have
      adopted to perform their practices. The rescue of those practices may lead health
      professionals to think about the current proposals to humanize delivery and
      childbirth.

PMID- 16894870
TI  - [Changes in the insulin application sites and in the syringes reutilized by
      diabetic patients].
AB  - A bibliographic research was carried out in the databases of LILACS, MEDLINE,
      SciELO and PubMed from 1978 to 2005 with the objective of identifying researches
      related to complications in the insulin application sites and in the discarded
      syringes reutilized by diabetic patients. The boolean expression "and" has been
      utilized in order to filter and to refine the descriptive and experimental works
      and the bibliographic revisions. The studies have been selected according to
      changes in the insulin application sites and in the discarded syringes that have
      been reutilized. The researches findings have been organized in a table according
      to the country of origin and to the type of study. 46,3% of the researches
      corresponded to data from the United States, 19,5% from England and 17% from
      Brazil.

PMID- 16894871
TI  - [Assessment and intervention in families assisted by the family health team].
AB  - This study aims at demonstrating the importance of using the Calgary Family
      Assessment and Intervention Model in the care practice of Family Health teams. It
      was carried out in a Family Health team, involving one family with a serious
      psychiatric disorder patient. The construction and application of instruments
      allowed establishing an intervention plan that led to behavioral changes. The
      conclusion is that this model can be used in family care. By using this model,
      families come closer to the health service and it becomes possible to plan the
      rendered care better.

PMID- 16894872
TI  - [Functional capacity and referred morbidity of elderly in an area covered by the
      Family Health Program].
AB  - This study aimed at characterizing the health perception, functional capacity and
      prevalence of self-referred diseases among the elderly in an area covered by the
      Family Health Strategy. The sample consisted of 86 elderly people (75 years or
      older) from a city in the north of Parana, Brazil. The data were collected in the
      second semester of 2004 by means of an adapted version of the OARS. 47.7%
      evaluated their health between good and excellent; 77.9% were independent; 76.7%
      presented co-morbidities. This article discusses the importance of the family
      health teams in the adoption of health preventive and promotional measures for
      the elderly and their families.

PMID- 16894874
TI  - [Health education as a nursing intervention strategy for diabetes bearers].
AB  - A descriptive study with the objective of analyzing an educational process as a
      nursing intervention strategy for diabetic persons approaching the
      Problematization Methodology assumptions and Paulo Freire's theoretical
      references on freedom of education. Nineteen Diabetes bearers from the town of
      Nova Aurora, State of Goias, Brazil, participated in the study over a 4-month
      period. The results evidenced that the dialogic educational activity was capable
      of contributing towards awakening the reflective, critical and creative potential
      of the group, presenting itself as an important intervention strategy for the
      nurse who works from the perspective of contributing for the patients'
      emancipation.

PMID- 16894873
TI  - [Life and working conditions among physicians at a university hospital].
AB  - This paper evaluated the life and working conditions of physicians who worked in
      a university hospital. Two questionnaires, one for occupational data and the
      Medical Outcomes Study 36 - Item Short-Form Health Survey (SF-36) were applied.
      91 surgeons and 96 physicians, mainly of the masculine sex, participated in the
      inquiry. The average age among surgeons was 44.5 and among physicians, 46. The
      average of weekly working hours was 51.8 hours among the surgeons and 44.1 among
      the physicians. 87.9% of the surgeons and 51.6% physicians also mentioned working
      in other hospitals. Only in Physical Aspects there was a significant statistical
      difference between the groups, with lower rates among physicians.

PMID- 16894875
TI  - [Group and group interaction in nurses' activities: a needed knowledge].
AB  - This study aimed at verifying the knowledge of nurses about groups and group
      functioning, as well as knowing which premises found their activities as
      coordinators of their working teams. The research was outlined by the descriptive
      exploratory approach, carried out in a university hospital in Porto Alegre,
      Brazil. The results show that 97% of the participants like group work while 77.7%
      of the nurses use both empirical and theoretical knowledge as the basis for their
      activities. However, most of them were unaware of the meaning of operative group
      and basic assumptions. By using the empiric and theoretical knowledge, the nurse
      can have tools to work with group emotions and support actions regarding the
      client's care.

PMID- 16894876
TI  - [Prevention of occupational accidents with biological material as per Green and
      Kreuter Model].
AB  - This study aimed at diagnosing the occurrence of occupational accidents deriving
      from exposition to biological substance among workers of a hospital from Sao
      Paulo, Brazil, analyzing the adopted safety measures and elaborating a flowchart
      of preventive actions according to the Health Promotion Model by Green and
      Kreuter. It is an exploratory study with data collected electronically from the
      website REPAT - Electronic Network for the Prevention of Occupational Accidents
      with biological substances. The strategy used by the hospital did not reduce the
      injures. Results were used to elaborate a flowchart of preventive actions in
      order to improve the workers' quality of life.

PMID- 16894877
TI  - [Nursing care program upon hospital admission and discharge].
AB  - This is a descriptive, five-year retrospective study intended at describing the
      work performed by two nurses in a surgical unit of Hospital de Clinicas de Porto
      Alegre, RS, Brazil, related to the Patients Admission and Discharge Preparation
      Program, where 2,588 patients were admitted from 1999 to 2003. The experience of
      this Program has been successful because, upon the admission, the nurse provides
      the patient with all the essential information regarding the hospitalization. In
      addition, the nurse develops the Nursing Process that comprises the individual
      care and the resulting preparation for the hospital discharge.

PMID- 16894878
TI  - [Quality of life among nursing professionals working in surgical wards].
AB  - This transverse, descriptive study aimed at evaluating the quality of life of
      nursing professionals working in the surgical ward, by using the Flanagan Quality
      of Life Adapted Scale. 103 workers participated in the study, mainly women
      (82.5%), with an average age of 38. Among them, 70.8% were nursing assistants
      while 11.6% were nurses. Regarding the quality of life evaluation, it has been
      found out a mean of 77.18 +/-10.51, a possible range from 16 to 112. The item
      with the highest rate of satisfaction was Relationship with Friends while
      Participation in Sports and Leisure Activities received the lowest satisfaction
      rate.

PMID- 16894879
TI  - [Assisting adolescent women: a report on an experience].
AB  - This paper reports the experience with a group of adolescent women in a Basic
      Health Center, in the municipality of Santa Maria, RS, Brazil, through an
      extension project developed by the teaching staff and the academicians of the
      Nursing and Psychology Courses of Universidade Federal do Rio Grande do Sul
      (UFSM), whose objective is carrying out integrated actions that provide spaces
      for reflection and discussion with adolescents. For such purpose, a participative
      methodology was adopted in which the adolescents effectively perform in the
      educational process. Didactical workshops provided dynamic activities on the
      themes and important reflections among the people involved, evidencing the
      relevance of the activities of this nature at the level of basic care.

PMID- 16894880
TI  - [Nursing teaching as a space for the development of health education
      technologies].
AB  - This article consists of a report on the experience of creating a new health
      educational technology against smoking invented by an academic of the Nursing
      School Graduation Course. The construction involved a problem solving
      methodology, with the participation of teachers, students, smokers and the
      community, in a constant process of teaching and learning, based on numberless
      interactions with the creative and critic responses obtained. It became clear
      that this technology is a powerful tool in the combat of smoking and that it can
      be adapted to different issues.

PMID- 16894881
TI  - [Fusion tags technology and their applications].
AB  - Fusion tags are originally developed to facilitate the purification of
      recombinant protein from crude extracts. In recent years, the discovery of
      different tags and the development of fusion strategy make the function of fusion
      tags diversified. However, there was no a cure-all fusion tag for different
      applications. We here give an overview of fusion tag technology and the different
      applications of fusion tags, including the purification, detection and oriented
      immobilization of recombinant protein, the visualization of bioevent in vivo, the
      enhancement of the yield of protein, the improvement of the solubility and
      stability of the expressed protein.

PMID- 16894882
TI  - [Improving phytase expression by increasing the gene copy number of appA-m in
      Pichia pastoris].
AB  - In order to improve the fermentation potency of phytase in recombinant host and
      decrease the production cost, the pichia expression vector pGAPZalpha-A was
      modified by introduction of an AOX1 promoter from vector pPIC9 and the resulted
      vector pAOXZalpha is an methanol induced vector. After that, a phytase gene appA
      m was cloned into pAOXZalpha to construct the recombinant vector pAOXZalpha-appA
      m. The recombinant Pichia pastoris 74#, which already contains one copy of appA-m
      and its fermentation potency exceeded 7.5 x 10(6) IU/mL, was used as the host
      strain for the transformation of pAOXZalpha-appA-m. The Pichia pastoris
      transformants were gained by electroporation. PCR results indicated that the appA
      m expression box has integrated into the genome of Pichia pastoris and the
      original construction of phytase gene has not changed. SDS-PAGE analysis revealed
      that phytase was overexpressed and secreted into the medium supernatant.
      Recombinants with high expression level were screened and used for fermentation.
      In 5L fermentor, the expression level of phytase protein achieved 4 mg/mL and the
      phytase activity (fermentation potency) exceeded 1.2 x 10(7) IU/mL, which was
      about 1.6-fold compared with that of the host strain 74#. Moreover, the improved
      recombinant Pichia pastoris is excellent at expression stability and heredity
      stability.

PMID- 16894883
TI  - [Knockout of the hprK gene in B. subtilis CcpA mutant and its influence on
      riboflavin fermentation].
AB  - In Bacillus subtilis , raising the amount of carbon catabolite in vivo would lead
      to carbon catabolite repression (CCR) and restrain the absorption of glucose. By
      deleting CcpA the CCR effect could be relieved, but the absorption of glucose
      remains restrained. The phosphoenol-pyruvate-sugar phosphotransferase system
      (PTS) is the main glucose transportation system in B. subtilis. HPr protein
      together with HprK/P participate in the glucose transportation. The HPr protein
      is phosphorylated at His-15 forming HPr-His-15-P transferring phosphate group
      from HPr to E II . While HprK/P phosphorylate HPr at Ser-46 forming HPr-Ser-46-P.
      HPr-Ser-46-P cannot participate in the transportation of glucose. The Knockout of
      ccpA gene increases the amount of fructose 1,6-bisphosphate(FBP) in vivo. And FBP
      could activate HPr kinase. So when CcpA is deleted, most part of the HPr will be
      phosphorylated at Ser-46. Absorpton of glucose is blocked. In this study, by
      disruption of hprk gene, the obtained B. subtilisZHc/pMX45 reaches the peak
      riboflavin production of 4.374mg/mL at the optimum glucose concentration of 10%,
      19.2% higher than that of B. subtilis24 A1/pMX45 at the optimum glucose
      concentration of 8%.

PMID- 16894884
TI  - [SCT-OGP fusion protein expression and its potential role as osteoporosis
      therapy].
AB  - Osteoporosis is a disease of bone metabolic disorder, the incidence of which
      increases sharply in old people. Calcitonin (CT) is a peptide hormone containing
      32 amino acid that can inhibit osteoclasts activity. Osteogenic Growth Peptide
      (OGP) is a peptide hormone with 14 amino acid. It is an autocrine mitogen for
      osteoblastic and firbroblastic cells which has anabolic activiy. Six SCT and OGP
      DNA segments were chemically synthesized and ligated into a yeast expression
      vector pPIC9. The recombinant plasmid was transformed into pichia pastoris GS115.
      Finally, we got two stable SCT-OGP high expression clones after screening.
      Purifed protein can stimulate the proliferation of osteoblastic and fibroblastic
      cells, and also stimulate serum ALP activity and decrease serum calcium level
      using mice as animal models, demonstrating its potential role in oteoporosis
      therapy.

PMID- 16894885
TI  - [Expression of the gene coding for a thermostable alpha-amylase from Pyrococcus
      furious in Chiamydomonas reinhardtii chloroplast ].
AB  - Thermostable alpha-amylase from Pyrococcus furious is an important industrial
      enzyme in brewing and alcohol production. Eexpression of the thermostable a
      amylase in plants can reduce greatly costs in the production of alcohol using
      crop plants. A chloroplast expression vector, p64A, containing the thermostable
      alpha-amylase gene from Pyrococcus furious, was constructed with clpP-trnL-petB
      chlL-rp123-rpl2 as Chlamydomonas reinhardtii plastid homologous recombinant
      fragments and spetinomycin-resistant aadA gene as select marker. The plasmid p64A
      was transferred into the chloroplast genome of C. reinhardtii by the biolistic
      method. Nine independently transformed lines were obtained by 100 mg/L
      spectinomycin selection. PCR amplification, Southern blot analysis of the
      transgene and cultivation in the dark all showed that the a-amylase gene had been
      integrated into chloroplast genome of C. reinhardtii. The activity of amylase
      expressed in the chloroplast of C. reinhardtii was detected by amylase activity
      assay and found to be as high as 77.5 u/g fresh weight of cells. These
      experimental results demonstrated the possibility of using transgenic
      chloroplasts of plant as bioreactors for production of industrial enzymes.

PMID- 16894886
TI  - [A novel binary vector to get marker-free transgenic plant].
AB  - A novel practical binary vector to get marker-free transgenic plant was
      constructed. The estrogen-inducible Cre/loxP DNA recombination system was adopted
      in this system. All non-target genes located between two identical orientation
      loxP sites could be excised from the transgenic genome by the Cre expression. In
      order to analyze this system, the target gene, GUS expression box (CaMV35s:
      :GUS), was inserted in the MCS outside the region franked by two loxP sites. Then
      it was introduced into the tobaccos. Results showed that the high-efficiency DNA
      recombination had take place and the target gene was working order after DNA
      excitation.

PMID- 16894887
TI  - [Construction and immunogenicity of recombinant adenovirus tandem expressing M
      and GP5 of porcine reproductive and respiratory syndrome virus].
AB  - The M protein gene of porcine reproductive and respiratory syndrome virus
      amplified by PCR was tandem linked with its GP5 gene in shuttle vector in correct
      frame, resulting in shuttle vector pShuttle-CMV-M-GP5. The positive clone was
      identified by PCR and further confirmed by sequencing. The constructed plasmid
      was linearized with Pme I and co-transformed BJ5183 host bacteria with pAdEasy-1
      to produce recombinant adenovirus DNA by homologous recombination. Then the
      adenovirus DNA was linearized with Pac I and transfected into HEK-293A cells to
      obtain recombinant adenovirus. The specific expression of target proteins by the
      recombinant adenovirus was verified by indirect immuno-fluorescence assay (IFA)
      with monoclonal antibodies against M and GP5.The results showed that the tandem
      linked M with GP5 could be co-expressed by adenovirus vector. Mice immunized with
      the constructed recombinant adenovirus induced strong humoral immunity (ELISA
      antibody and virus neutralizing antibody) and cellular immunity (lymphocyte
      proliferation and CTL responses). The results showed that the recombinant
      adenovirus has strong immunogenicity and provided the basis for the further
      experiments in pigs.

PMID- 16894889
TI  - [Overproduction of glucoamylase by recombinant Aspergillus niger harboring
      multiple copies of glaA].
AB  - The glucoamylase gene (glaA) of Aspergillus niger CICIM F0410 was cloned,
      sequenced and expressed. The integrated plasmid pBC-Hygro-glaA carrying the glaA
      was constructed and transformed into A. niger F0410. Transformants with multiple
      copies of glaA integrated in the chromosome were selected by 150 microg/mL
      hygromycin B and identified by real-time PCR. Two to three multiples of glaA in
      the chromosome were found to be optimal for higher expression of glucoamylase.
      Shake-flask fermentation under optimal conditions showed that glucoamylase
      secreted by the transformant GB0506 was 17.5% higher than parental strain F0410
      at the end of fermentation. In conclusion, increasing copy number of glaA by
      chromosomal integration significantly improves the yield of glucoamylase in the
      industrial strain of A. niger.

PMID- 16894888
TI  - [Cloning and expression of Oreochromis aurea gonadotropin-releasing hormone cDNA
      in Escherichia coli and its immunogenicity for mice].
AB  - To study the function of the GnRH protein, the recombinant pMAL-GnRH was
      constructed and expressed in TB1 E. coli. The cDNA encoding gonadotropin
      releasing hormone (GnRH) and GnRH associated peptide (GAP) was amplified from
      total RNA of O. aurea pituitary glands by reverse transcription polymerase chain
      reaction (RT-PCR), and then blasted against other GnRH cDNA sequences in the
      GenBank. The analysis of the sequence data indicated that the coding region of
      the cDNA fragment, which encoded 89 amino acid residues, was about 400 bp in
      size. The amplified cDNA fragment was cloned into the prokaryotic expression
      vector, pMAL-c2x, to produce the expression vector pMAL-GnRH. The recombinant
      plasmid was transformed into E. coli TB1. GnRH-MBP fusion protein was obtained
      after the addition of IPTG into the growth media. SDS-PAGE analysis revealed that
      the GnRH-MBP was expressed after induction with IPTG for 4 h. A protein band of
      56 kD appeared on SDS-PAGE gel and was proved by Western blot. The mass
      production of the recombinant protein was about 41.6% of total bacteria protein.
      After purification and cleavage of the fusion protein purified GnRH protein could
      be obtained. Then the fusion protein was used to immunise some ICR mice to
      produce anti-GnRH antibody. This fusion protein could significantly elicit
      specific antibody response in immunized mice compared with the blank groups, and
      the titers against GnRH reached peak 0.707 +/- 0.320 at the 5th week after
      immunization. These results demonstrated that recombinant protein could induce
      high GnRH antibody responses in laboratory animals.

PMID- 16894891
TI  - [A method using long primers for cloning the upstream sequence of delta-6 fatty
      acid desaturases gene of Thamnidium elegans by nested inverse PCR].
AB  - Thamnidium elegans is a kind of phycomycete that produces essential unsaturated
      fatty acids, particularly y-linolenic acid. In this process, delta6-Fatty acid
      desaturase (D6D) plays a key role due to its enzymatic properties that catalyze
      the delta6 site dehydrogenation of precursor linoleic acid (18:2delta(9, 12) n-6)
      and a-linolenic acid (18:3delta(9, 12, 15) n-3). This reaction is the first and
      rate-limiting step of highly unsaturated fatty acids (HUFA) synthesis pathways.
      After we have isolated and cloned the gene coding delta6-fatty acid desaturase
      from Thamnidium elegans As3.2806 (GenBank accession number DQ099380), our
      interest focuses on the promotion and regulation of the gene transcription. To
      achieve this aim, we designed long primers and used nested inverse PCR to amplify
      DNA flanking sequences. First, genome of Thamnidium elegans was extracted and
      digested with restriction enzymes EcoR I and Kpn I , respectively. Then we
      ligated the digested DNA with T4 ligase at low concentration which is propitious
      for linear DNA to joint intromolecule. According to the sequence of delta6-fatty
      acid desaturase gene of Thamnidium elegans, we designed a couple of 35nt long
      inverse primers and two couples of shorter inverse primers for inverse PCR. Three
      rounds of PCR reactions were performed. In the primary reaction, the ligated DNA
      was used as a template, and the product was used as the template of the secondary
      reaction, the tertiary reaction was achieved in the same way. After all the three
      rounds of reactions, we got a nice product about 4 kb from the EcoR I digested
      sample, in which a 1.3kb 5' upstream sequence (GenBank accession number DQ309425)
      of delta6-fatty acid desaturase gene containing several putative regulatory
      elements including TATA. box, FSE-2, AP-1 sites, CCAAT cis-element site and STRE
      binding site was derived after sequencing. All of these implied intensely that
      this 1.3kb fragment is a condition-regulated promoter. It is the first report
      about Thamnidium elegans detla6-fatty acid desaturase gene promoter. The
      procedure described here is a rapid and simple method and particularly useful to
      isolate flanking sequences from fungal genome. box, FSE-2, AP-1 sites, CCAAT cis
      element site and STRE-binding site was derived after sequencing. All of these
      implied intensely that this 1.3 kb fragment is a condition-regulated promoter. It
      is the first report about Thamnidium elegans delta6-fatty acid desaturase gene
      promoter. The procedure described here is a rapid and simple method and
      particularly useful to isolate flanking sequences from fungal genome.

PMID- 16894890
TI  - [Improvement of baculovirus expression system and purification of IL-6 protein
      expressed in insect cells].
AB  - Based on site-specific transposition of an expression cassette into a baculovirus
      shuttle vector (Bacmid) which propagated in Escherichia coli, the Bac-to-Bac
      System provides a rapid and efficient method to generate recombinant
      baculoviruses and is widely used for high level expression of heterologous
      proteins. And the efficiency of recombinant baculovirus infecting cells plays an
      important role on the protein expression. In this study, we introduced an EGFP
      expression cassette driven by polyhedrin promoter into the p74 locus of Bacmid by
      homologous recombination. The target Bacmid-egfp was then transformed into E.
      coli DH10B containing the transposition helper plasmid to gain a new
      transposition receipt strain E. coli DH10Bac-egfp. Because of the intact attTn7
      sites and lacZ', target gene cloned in a pFastBac vector can be transposed into
      the Bacmid-egfp shutter vector to construct recombinant baculovirus, which would
      allow the tracing of the target protein expression and the recombinant Bacmid
      transfection or recombinant baculoviral infection under fluorescence microscopes.
      Recombinant virus Bac-egfp-DsRed was constructed by transposing DsRed into the
      Bacmid-egfp in E. coliDHl0Bac-egfp, and the Sf9 cells infected with the
      recombinant virus expressed DsRed and EGFP efficiently. Another protein IL-6
      fused with 6 x his tag was expressed and purified sucessfully from Sf9 cells
      infected with recombinant virus Bac-egfp-6 x his-IL6 constructed by the improved
      Bac-to-Bac system.

PMID- 16894892
TI  - [Cloning of distinguishing DNA sequences of Gastrodia elata Blume and application
      of them in identifying gastrodia tuber].
AB  - Gastrodia elata Bl. is a famous and costful traditional Chinese medicine. Their
      genomic DNA fingerprints were investigated using a modified Randomly Amplified
      Polymorphic DNA method. DNA fragments common to all or to fine populations were
      identified and recovered. Five DNA fragments were proven not to be reported
      through DNA cloning, PCR identifying, nucleotide sequencing and bioinformatics
      analyses and were received in and recorded by NCBI GenBank. Gastrodine contents
      of the Gastrodia tuber samples were determined using high performance liquid
      chromatography technique. The distribution of the five DNA fragments in 9
      Gastrodia elata Blue populations and the correlation with gastromedicine content
      were studied. The results show the distribution of these DNA sequences varied
      greatly among the populations whereby DNA Sequence 1 was the common and
      distinguishing molecular marker for all the populations studied and DNA Sequence
      2 may relate to higher gastrodine content. In conclusion, these DNA marker
      sequences can be employed to identify genuine gastrodia tubers, better varieties
      and optimize their selection and cultivating.

PMID- 16894893
TI  - [Cloning and expression of pokeweed antiviral protein-II gene from the summer
      leaves of Phytolacca amercana].
AB  - The cDNA sequence encoding pokeweed antiviral protein-II was cloned from the
      fresh summer leaves of phytolacca amercana by RT-PCR. The recombinant PAP-II was
      subcloned into the expression vector pET-28a(+) and expressed in E. coli BL21
      after IPTG induction. SDS-PAGE analysis showed that the expressed PAP-II existed
      in the form of inclusion bodies. The purified fusion protein was obtained after a
      series of steps including cell break, inclusion body solubilization, protein
      refolding and purification through BBST NTA resin column. The non-radioactive
      ELISA-based HIV-1 integrase assay showed that the recombinant pokeweed antiviral
      protein-II and RTA were able to inhibit HIV-1 integrase to some extent (IC50 =
      303 microg/mL, 220 microg/mL respectively). MTT assay showed that cytotoxicity of
      pokeweed antiviral protein II for HEP-G2 cells and Hela cells was in a dose
      dependent manner with IC50 s of 93 microg/mL and 102 microg/mL, respectively. The
      results suggested that pokeweed antiviral protein-II is a potent anti-tumor
      candidate. The finding of integrase inhibitory activity and the discovery of
      cytotoxicity provide more insights into the anti-HIV and the anti-tumor
      activities of PAP-II.

PMID- 16894894
TI  - [Prokaryotic expression of fusion protein TAT-EDAG and study on its transduction
      activity].
AB  - HIV-TAT protein transduction domain (PTD) is a new kind of peptide that is
      responsible for transduction of proteins through the plasma membrane with high
      efficiency. Linked covalently to proteins, peptides, nucleic acid, it could
      transduce into nearly all kinds of cells and tissues with high efficiency and
      without any damages. In this study, we constructed the TAT-EDAG and TAT-GFP
      prokaryotic expression vectors and expressed soluble TAT-EDAG and TAT-GFP fusions
      in E. coli BL21 (DE3) successfully. By using the Ni-NTA-agrose purification
      system under the native condition we got the purified fusion proteins whose
      purification were higher than 90%. After desalting we found the TAT-GFP could
      transduced successfully into the mouse fibroblast cells and the TAT-EDAG could
      transduced into HL-60 cells in vitro. It will be useful to amplify the HSCs in
      vitro in the next step.

PMID- 16894895
TI  - [Simultaneous expression of modified hepatitis B surface antigen fusion
      polypeptides containing preS1, preS2 epitopes in Pichia pastoris].
AB  - At present time, the widely used hepatitis B virus( HBV) vaccines consist of only
      the small hepatitis B surface antigen expressed in yeast or CHO cells. The
      frequency of non-responders to these vaccines has increased the demand for a more
      immunogenic vaccine. Some studies have suggested that the addition of preS region
      to the vaccine will improve its efficacy. However, the large protein (L)
      containing the whole preS region can not be effectively expressed in vitro. To
      overcome this problem, two chimeric contructs, SS1, surface gene containing preS1
      region at C-terminus and SS2, surface gene containing preS2 region at C-terminus,
      were constructed and effectively expressed in our previous studies. Here we
      further constructed an expression vector containing both SS1 and SS2 expression
      cassettes by separation and ligation the SS2 cassette to a linearized SS1
      expression vector pAO815-SS1. The recombinant vector was transformed into Pichia
      pastoris GS115 by electroporation. A high-level expression strain (GS115-SS1S2)
      was established by primary screening for His+ transformants and further analysis
      for induction products. ELISA results demonstrated that the expressed protein had
      S, preS1 and preS2 antigenicities simultaneously. Western blotting showed that
      the product can bind to all of the three antibodies, anti-S, anti-preS1 and anti
      preS2. The expression protein was present in the form of particles of 20-35 nm
      diameter and the yield of recombinant particles reached 300-600 mg/L by
      fermentation. The SS1 and SS2 polypeptides kept intact in purified particles,
      suggesting that the stability of preS region has been significantly improved.

PMID- 16894896
TI  - [Studies on relationship between the expression of hTNF-alpha gene and
      photosynthesis in Anabaena sp. IB02].
AB  - The effects of illumination on growth of Anabaena sp. IB02 and hTNF-alpha
      expression were studied. Photosynthetic activity, PS I and PS II activity of
      Anabaena sp. IB02 were assayed. Illumination enhanced the growth of Anabaena sp.
      IB02 and hTNF-a expression. Some relations were observed between hTNF-alpha
      expression and ture photosynthesis activity, PS I, PS II activity of Anabaena sp.
      IB02. Significant differences of the photosynthetic activity of host were
      detected simultaneously when hTNF-a expressed: the respiration rate increased (
      68%), the light saturation point descended (+66%), all these suggested that the
      metabolic charge of host were increased and grow faster than wild type under low
      illumination.

PMID- 16894897
TI  - [Effect of phosphate on growth and polysaccharide production by suspension
      cultures of protocorm-like bodies of Dendrobium huoshanense].
AB  - The effect of inorganic phosphate on cell growth, accumulation of polysaccharides
      together with nutrient utilization was investigated in suspension cultures of
      protocorm-like bodies of Dendrobium huoshanense. Thirty-day-old cells were
      transferred into liquid medium with the inoculum density of 100 g/L cells. The
      results indicate that the optimal concentration of phosphate in medium for cell
      growth of protocorm-like bodies of Dendrobium huoshanense was 2.5 mmol/L and
      biomass was 496.5 g/L (fresh weight). Phosphate was a limited factor for cell
      growth and there was relationship between the levels of intracellular phosphate
      and cell growth. 2.5 mmol/L of medium phosphate was beneficial to the absorption
      of carbohydrate and nitrate source. 0.312 mmol/L of medium phosphate was better
      for accumulation of polysaccharides and production of polysaccharides was 2.22
      g/L at 36 d.

PMID- 16894898
TI  - [Effects of exogenous phytohormones on hairy root growth and biosynthesis of
      anthraquinones in the hairy root culture of Polygonum multiflorum].
AB  - The effects of exogenous phytohormones on hairy root growth and biosynthesis of
      anthraquinones in the hairy root cultures of Polygonum multiflorum Thunb. were
      studied. The results showed that the 2,4-D, NAA and 6-BA all have obvious effects
      on the growth of hairy root cultures and the biosynthesis of anthraquinones. The
      growth of hairy root and biosynthesis of anthraquinones were strongly restrained
      by 2,4-D. However, NAA and 6-BA of appropriate concentration were favourable to
      hairy root growth and anthraquinones production.

PMID- 16894899
TI  - [Effects of cu2+ on biosynthesis of camptothecin in cell cultures of Camptotheca
      acuminata].
AB  - Camptothecin is a strong anti-tumor compound isolated from Camptotheca acuminata.
      One of the most important way for the production of Camptothecin is by cell
      cultures of Camptotheca acuminata. The effect of Cu2+ on camptothecin
      accumulation in Camptotheca acuminata cell line was described in this paper. The
      results showed that the optimum CuCl2 concentration in B5 medium was 0.008 mg/mL,
      which increased camptothecin production for 30 times compare to the control while
      has no inhibitive effects on cell growth, at the same time, the peroxidase
      activity was increased and the anthocyanidin accumulation was inhibited. The
      promotive effects of Cu2+ on camptothecin accumulation in light was higher than
      that in dark.

PMID- 16894901
TI  - [Purification and properties of isoflavone-glucosidase].
AB  - A high activity isoflavone-glucosidase, which hydrolysis glycosides, was obtainde
      using liquid fermentation from Absidia sp. R strain. The isoflavone-glucosidase
      was purified 11 folds with yielding rate of 10.9% after ammonium sulfate
      precipitation and DEAE-Cellocuse (DE-52) ion exchange chromatography. SDS-PAGE
      results showed that the molecular weight is 53kD. And the optimum temperature,
      the optimum pH, Km and pI of the enzyme are 50 deegrees C, 5.0, 1.3 x 10(-2)
      mol/L and 3.2, respectively. The isoflavone-glucosidase is also rather stable
      under 60 degrees C and in pH range from 5.0 to 7.0. The enzyme can be activated
      by Co2+ and Ca2+, and be inhibited by Ag+ and Cu2+.

PMID- 16894900
TI  - [Production of polyclonal and monoclonal antibodies against citrus tristeza virus
      and their efficiency for the detection of the virus].
AB  - Citrus tristeza virus (CTV) was purified from a citrus sample by a modified
      protocol, and the yield was about 1 mg from 100 g citrus tissues. Polyclonal
      antibody was prepared by immunizing rabbits with the purified CTV preparation
      with a titer 1:25600 in indirect ELISA test. Eighteen hybridoma-cell lines
      secreting monoclonal antibodies (MAbs) against CTV were screened after the fusion
      of mouse myeloma cells (SP2/0) with spleen cells from BALB/c immunized with the
      virus preparation. Four hybridoma-cell lines were selected randomly for later
      analysis. The results indicated that the titers of ascetic fluids against these
      hybridoma cell lines ranged from 1:51200 to 1:204800 in indirect ELISA, and their
      isotypes and subclasses were IgG2a for 2G and 3H and IgG2b for IE and 4H. These
      four Mabs were used to detect CTV in citrus samples in different sources. Results
      showed that TAS-ELISA with polyclonal antibody as trapping antibody and
      monoclonal antibody as testing antibody had a higher specificity and sensitivity
      than PAS-ELISA. Four Mabs showed different intensities of serological reaction
      with different CTV isolates. However, much work remains for realizing the
      characteristics and the serological relationships among these isolates.

PMID- 16894902
TI  - [Purification and biochemical character of a fibrinolytic protein from
      Eupolyphaga sinensis].
AB  - A novel of fibrinolytic protein has been separated and purified by ammonium
      sulfate fractionation, DEAE-cellulose and SephadexG-75 Column chromatography from
      the tissue of the female Eupolyphaga sinensis in the paper. The protein showed an
      apparent molecular weight of 41.3 kD on sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis analysis. In addition, it includes 10.5% sugar. Its specific
      activity to hydrolyze fibrin was 547.86 u/mg. The enzyme activity was inhibited
      by Mg2+, Ca2+, protein inhibitors, such as 8mol/L urea and 1% beta
      mercaptoethanol, and serine protease inhibitor such as phenylmethanesulfonyl
      fluoride (PMSF), but wasn't inhibited by Na+, K+ and ethylenediaminotetraacetic
      acid (EDTA). The protein was stable under 40 degrees C and it's optimal
      temperature was also 40 degrees C. It's optimal pH was 8.0. It showed a different
      way between the activity and UK when they degrade the plasminogen. Based on all
      the messages the protein can be suggested to be a novel fibrinolytic protein.
      There have been no such component of fiberinolytic enzyme from Eupolyphaga
      sinensis walker reported yet.

PMID- 16894903
TI  - [Isolation and identification of lipopeptides produced by Bacillus subtilis
      fmbJ].
AB  - Isolation and idenfication of lipopeptides from Bacillus subtilis fmbJ was
      carried out in this paper. With HPLC method, it was determined that the
      antimicrobial substance was composed of many components, and one of them had the
      similar retention time similar to surfactin. In addition, the antimicrobial
      substance was proved to include the closed cycle peptide bind by TLC, and one of
      them had the migrating rate similar to surfactin. Furthermore, ESI-MS analysis
      showed that the antimicrobial substance contained five homologues of fengycin,
      such as m/z1449.9, m/zl1463.8, m/zl1477.8, m/z1491.9 and m/z1505.9, and three
      homologues of surfactin, such as m/z1008.8, m/z1022.8 and m/z1036.8.

PMID- 16894904
TI  - [Optimized culture medium and fermentation conditions for lipid production by
      Rhodosporidium toruloides].
AB  - Culture medium and fermentation conditions for lipid production by Rhodosporidium
      toruloides were optimized with single factor and uniform design experiment. The
      best medium recipe was found with 70 g/L glucose, 0.1 g/L (NH4)2SO4, 0.75 g/L
      yeast extract, 1.5 g/L MgSO4. 7H2O, 0.4g/L KH2PO4, sterilized at 121 degrees C
      for 15 min, and then supplemented with ZnSO4 1.91 x 10(-6) mmol/L, CaCl2 1.50
      mmol/L, MnCl2 1.22 x 10(-4) mmol/L and CuSO4 1.00 x 10(-4) mmol/L. The optimal
      fermentation conditions were as follows: 50 mL of medium (pH 6.0) in 250 mL
      Erlenmeyer flask with 10% inoculum (28h) under orbital shaking at 200 r/min for
      120h at 30 degrees C. Under these conditions, yeast biomass accumulated lipids up
      to 76.1%.

PMID- 16894905
TI  - [Optimization of SRAP & ISSR technology and its application in the identification
      of seeds of Brassica oleracea L].
AB  - In this study, the molecular marker technology of SRAP and ISSR were applied in
      rapid identification of seeds from eight species of Brassica oleracea L. Firstly,
      using the genomic DNA of cabbage as template, SRAP and ISSR reaction systems were
      optimized through testing every factor, respectively, that affects PCR
      amplification. Then, using the optimized reaction systems, 30 SRAP primer pairs
      and 15 ISSR primers were applied to amplify genomic DNA of cabbage, savoy, purple
      cabbage, borecole, cauliflower, broccoli, Brussels sprouts, and kohlrabi The
      results showed that high polymorphisms were exhibited among the eight species of
      Brassica oleracea L. by SRAP primer pairs of M3-E5 and M4-E5, as well as ISSR
      primers of 844 and 888, especially primer 844 which can identify all eight
      materials efficiently.

PMID- 16894906
TI  - [Hydroxylation of 16alpha, 17alpha-epoxy-4-pregenene-3, 20-dione by Absidia
      coerulea with pseudo-crystallo feed].
AB  - The 11-hydroxylation of 16alpha,17alpha-epoxy-4-pregenene-3,20-dione as a useful
      intermediate for the preparation of hormones can be achieved by the mycelium of
      Absidia coerulea at higher conversion rate than using other strains. In this
      paper 16alpha,17alpha-epoxy-4-pregenene-3,20-dione mixed with a little water,
      beta-cyclodextrin, Tween-80 was introduced into the fermentation broth after
      ultrasonication to increase pseudo-water-solubility of the hydrophobic substrate.
      This pseudo-crystallo feed could avoid the toxicity of organic solvents and was
      more available for the microbial transformation. The multi layer feed-forward
      neural network was used to setup a model which indicated the relationship between
      medium and feed components and the conversion rate. Particle swarm optimization
      (PSO), which was a stochastic global optimization algorithm and of which the
      convergence speed was high, was applied to obtain the optimal concentration of
      the medium and feed components. At optimum conditions with the pseudo-crystallo
      feed, the conversion rate of 16alpha,17alpha-epoxy-4-pregenene-3,20-dione at an
      initial concentration of 10 g/L was 87.5% in shaking flasks. The conversion rate
      of the substrate was up to 86.6% at higher concentration of 20 g/L feed in a 3.7
      L fermentor.

PMID- 16894907
TI  - [The effect of NAD kinase homologues on the beta-oxidation of unsaturated fatty
      acids with the double bond at an even position in Saccharomyces cerevisiae].
AB  - ATP-NAD kinase phosphorylates NAD to produce NADP by using ATP, whereas ATP-NADH
      kinase phosphorylates both NAD and NADH. Three NAD kinase homologues, namely,
      Utr1p, Pos5p and Utr1p, exist in the yeast Saccharomyces cerevisiae, which were
      all confirmed as ATP-NADH kinases and found to be important to supply NADP(H) for
      yeast cells. In S. cerevisiae, fatty acid beta-oxidation is restricted to
      peroxisomes and peroxisomal NADPH is required for beta-oxidation of unsaturated
      fatty acids with the double bonds at even positions. Single and double gene
      disruption strains of NAD kinase genes, i.e., utr1, pos5, yef1, utr1yef1,
      utr1pos5 and yef1pos5 were constructed by PCR-targeting method. The utilization
      ability of these mutants for unsaturated fatty acids with the double bonds at
      even or uneven positions was examined, with wild type BY4742 as positive control
      cell, and fatty-acyl-CoA oxidase gene deletion mutant (fox1) and peroxisomal NADP
      dependent isocitrate dehydrogenase isoenzymes gene deletion mutant (idp3) as
      negative control cells. The results indicated that the NAD kinase homologues,
      especially Pos5p, were critical for supplying NADP and then NADPH in peroxisomal
      matrix. NADP, which was supplied mainly by Utr1p, Pos5p and Yef1p, particularly
      by Pos5p, was proposed to be able to transfer from outside of peroxisome into
      peroxisomal matrix and then converted to NADPH by Idp3p.

PMID- 16894908
TI  - [Three-dimensional spheroid model for cultivating WB-F344 cells in simulated
      microgravity].
AB  - Three-dimensional (3D) culture of cells could closely mimic the in vivo situation
      with regard to cell function and microenvironment compared with plane monolayer
      cultured cells. In this paper, we established 3D culture of rat WB-F344 cells
      with rotary cell culture system (RCCS) to simulate microgravity environment, and
      examined cells proliferation, morphology, microstructure, E-cadherin protein
      quantity and mRNA expression of adhesion molecules by count the number of cells,
      optical microscope, transmission electron microscope and reverse transcriptase
      polymerase chain reaction (RT-PCR). The results demonstrated that cells were
      polyhedron with lots of micovilli and mitochondria, which grow well and packed
      together densely to form irregular aggregates. Adjacent cells were connected with
      desmosome and tight junction. With the regard, the aggregates behaved 3D growth
      characteristics. Moreover, compared with control, mRNA level of Fibronectin and E
      cadherin protein were increased, the changes maybe is the part mechanism in this
      microgravity simulated cells culture models which strengthened cells junction.
      This rotating 3D model might facilitate the study of interactions of cell-cell,
      cell-matrix and the mechanisms.

PMID- 16894909
TI  - [Porcine follistatin cDNA cloning and expression in Escherichia coli].
AB  - The total RNA was extracted from porcine ovary. Porcine Follistatin cDNA was
      cloned by RT-PCR. Complete porcine follistatin cDNA coding sequences are
      presented including 1038 bp of open reading frame. The purified porcine
      follistatin cDNA was inserted into pGEX-4T-3 vector to construct the prokaryotic
      fusion protein expression vector. The recombinant expression plasmid was
      transformed into BL21 (DE3) and expression was induced by IPTG. Protein products
      were detected by SDS-PAGE and confirmed by Western blotting analysis, which
      showed that the yield of the Follistatin cDNA was a 63kD protein expression
      vector. Follistatin protein was expressed in the form of glutathione-S
      transferase (GST) fusion protein in E. coli.

PMID- 16894910
TI  - [Molecular cloning of an amidase gene from Nocardia sp. and its expressionin
      Escherichia coli].
AB  - The amidase of Nocardia sp. is one of important industrial enzymes. Based on DNA
      and protein sequence alignment from different strains, a new gene of amidase was
      successfully cloned from Nocardia YS-2002, which is widely used for industrial
      production of acrylamide in China. DNA sequence analyses showed that the 1466bp
      cloned-fragment contains promoter, open reading frame and terminating-palindrome.
      Protein sequence alignment and phylogenetic tree analyses showed that the amidase
      coming from Nocardia sp. YS-2002 is a kind of specialamidase, without the typical
      conserved sequence of the amidases. Enzymatic characteristics predictions
      indicated that the molecular weight and pI of the new amidase is approximately
      38.05 kD and 4.88, respectively, and it would be stable when heterogeneously
      expressed in E. coli. By inserting the ORF of the amidase into plasmid pET
      28a(+), a recombinant strain, pEAB, was selected using E. coli BL21(DE3) as the
      host. SDS-PAGE analyses of both the whole cells and ultrasonic-treated cells
      confirmed the feasibility of the heterogeneous expression of amidase in the
      recombinant E. coli. But the activity of amidase in E. coli BL21(DE3) not more
      than 0.5 u/mg, because most of the enzymes expressed were formed as inclusion
      bodies.

PMID- 16894911
TI  - [Screen of media for insect cells (HzAm1) growth and its adaptation to low serum
      culture].
AB  - Insect cell-baculovirus system is a useful tool for both insecticidal virus
      production and the expression of medically useful foreign genes. Serum-free
      culture or low serum culture for insect cells is essential and significant. Media
      for the growth of insect cells HzAm1 from three kinds of commercial media TC
      100,GRACE and IPL-41 with 10% serum were investigated and screened. The result
      shows that medium TC-100 is the most suitable medium for the growth of cells
      HzAm1. Adaptation of insect cells HzAm1 to cultures in medium TC-100 with serum
      reduction from 10% to 1% was carried out as cultures were supplemented with
      lactalbumin hydrolysate and yeastolate etc. Growth of insect cells HzAml in
      medium TC-100 with serum 1%, lactalbumin hydrolysate and yeastolate was well.

PMID- 16894912
TI  - [Studies on spermatogonial stem cells cultured in vitro of Wuzhishan Mini
      Porcine].
AB  - The isolation and culturation of SSCs of different stage of Wuzhishan Mini
      Porcine (WZSP) with different way of enzymatic digestion and culturation were
      deaded in this study. The results of the experiment described are as the
      following: The proper time of isolation and culturation of SSCs of WZSP is 1-20
      old days. Different old of piglets with different method. Using DMEM medium as a
      fundmental culture medium add different gradient at 34 degrees C in a water
      saturated atmosphere of 95% air, 5% CO2. The mulberry-shaped SSCs clusters
      appeared as original generation in 7-8 days culture. The SSCs clusters developed
      half-suspendedly in the culture medium. SSCs alkaline phosphatase (AKP) staining
      expressed positively. Mouse embryonic fibroblast was used as feeder layer for the
      SSCs passage cultured, The SSCs show good attached attributes, but the number of
      SSCs decreased quickly after 4 days culture. By seminiferous cord fragment
      culturation can also appear SSCs clusters in 5 days, The SSCs clusters developed
      half-suspendedly in the culture medium. In addition, the testes placed in cold (4
      degrees C) PBS banlanced salt solution for 24 h also can be used as a good
      matierials for preparation of SSCs. These results indicate that the method of
      solation and culturation of SSCs are very correct and efficient, all these can be
      utilized as a good reference for future studies.

PMID- 16894913
TI  - U of L partnership helps backside workers stay healthy as a horse.

PMID- 16894915
TI  - Opportunity unlimited?

PMID- 16894916
TI  - Stolen lives.

PMID- 16894917
TI  - Leading by example.

PMID- 16894918
TI  - Going for goals.

PMID- 16894919
TI  - Offer us what we want.

PMID- 16894920
TI  - A recipe for psychiatry pie in the sky.

PMID- 16894921
TI  - Human rights legislation plays an increasingly significant role in health and
      social care services.

PMID- 16894922
TI  - Welfare rights and mental health.

PMID- 16894923
TI  - This life. Interview by Suzy Johnston.

PMID- 16894924
TI  - Justice for women.

PMID- 16894925
TI  - Choice and decision-making.

PMID- 16894926
TI  - Help us do it our way.

PMID- 16894927
TI  - Woman on the verge.

PMID- 16894928
TI  - Mental health problems on television.

PMID- 16894929
TI  - [Expression of multi-copy and immuno-reactivity of recombinant type-specific
      epitope of herpes simplex virus type 1].
AB  - OBJECTIVE: To express a multi-copy specific epitope recombinant protein of herpes
      simplex virus type 1 (HSV-1) with immuno-reactivity. METHODS: Multi-copy genes
      with a specific epitope of HSV-1-glycoprotein G 112-127 were constructed by DNA
      recombination and cloned in E. coli JM109 pGEM-5Zf. The positive recombinants
      were determined by SDS-PAGE and Western blotting. RESULTS: The recombinants with
      4, 8, 16 and 32 copies of gG 112-127 were obtained. The 8-copy recombinant was
      expressed by 17.5%, mainly as inclusion body. And it reacted with antiserum HSV
      1, but not with antiserum HSV-2. CONCLUSION: The HSV-1-gG112-127 recombinant
      could be used to distinguish HSV-1 and HSV-2 in ELISA.

PMID- 16894930
TI  - [Epidemiological study of chronic prostatitis patients with depression symptoms].
AB  - OBJECTIVE: To study the depression symptoms in chronic prostatitis (CP) patients,
      and explore the correlation between depression symptoms and CP. METHODS: The Zung
      self-rating depression scale (SDS) , NIH-CPSI, IIEF-5, and a self-designed
      questionnaire were employed in 1500 cases of CP patients. RESULTS: A total of
      1426 effective questionnaires were collected. The mean score of SDS was (44.24 +/
      10.20), significantly higher than that of the domestic norm (P = 0.000). With
      the score limitation set at > or = 53, 309 (21.7%) of the CP patients had
      symptoms of depression, of whom 176 (12.3%) were rated by SDS as in the mild, 114
      (8.0%) in the moderate and 19 (1.3%) in the severe state of depression. The
      dominating symptoms as listed in SDS were exactly the stimulating and provoking
      factors of CP. The scores of SDS were significantly correlated with disease
      course, CPSI score, IIEF score and times and cost of treatment (P < 0.01), while
      no correlation was observed with age and WBC counts in EPS. CONCLUSION: CP
      patients mostly have depression problems, which are closely correlated with CP
      and contribute to the recurrence, refractoriness and discontinued outcome of the
      disease.

PMID- 16894931
TI  - [In-vitro differentiation of human testicular round spermatids to elongating
      spermatids].
AB  - OBJECTIVE: To investigate the differentiation of human testicular spermatogenic
      cells during in vitro culture. METHODS: Testicular cells of obstructive
      azoospermic patients' testis biopsies were dispersed employing mechanic methods.
      Then, (1) mixed testicular cells were applied to in vitro culture, and changes of
      the ratio of elongating spermatids and all round cells were analyzed during mixed
      cell culture; (2) round spermatids were picked up from the mixed cells employing
      micromanipulator, followed by differentiation of the isolated round spermatids
      during microdrop culture. RESULTS: The ratio of the elongating spermatids
      increased significantly (P < 0.05) after 24 hours of mixed cell culture in HTF
      medium supplemented with FSH and testosterone. During single round spermatid
      culture, transformation of the round spermatid to elongating spermatid with newly
      formed flagellum was observed, and the transformation ratio within 48 hours of
      microdrop culture was 3.54%. The differentiation of human testicular
      spermatogenic cells cultured in Vero cell conditioned medium was similar to that
      cultured in HTF medium. CONCLUSION: Human testicular round spermatids can
      differentiate to elongating spermatids during in vitro culture. Vero cell
      conditioned medium does not promote the differentiation of human testicular round
      spermatids to elongating spermatids.

PMID- 16894932
TI  - [Relationship between sperm motility parameters and sperm morphology].
AB  - OBJECTIVE: To evaluate the relationship between sperm motility parameters and
      sperm morphology. METHODS: Seven hundred and eighty-three semen samples were
      tested. Sperm motility parameters were analyzed by computer-aided sperm analysis
      (CASA) , and sperm morphology assessed by automated sperm morphology analyzer
      (ASMA). The cases were classified based on the World Health Organization
      criteria. Morphologically 241 of the samples were normal and the other 542
      abnormal. RESULTS: VCL, WOB, VAP of the morphologically abnormal group were
      significantly higher than those of the normal group (P < 0.05, P < 0.001), while
      MAD, LIN, STR of the abnormal group were significantly lower (P < 0.05, P <
      0.001). There were significant positive correlations between the morphologically
      normal sperm rates and MAD, LIN, WOB, STR, and a significant negative correlation
      between the morphologically normal sperm rate and ALH. CONCLUSION: Morphological
      abnormality of sperm is often accompanied with weak motility, which is probably
      attributed more to some factors that coact on both sperm motility and morphology
      than to the influence of sperm morphological abnormality on sperm motility.

PMID- 16894933
TI  - [Effects of flunarizine on T-type calcium channels in mouse spermatogenic cells].
AB  - OBJECTIVE: To investigate the effects of Flunarizine (Flu) on T-type calcium
      currents (ICaT) in spermatogenic cells. METHODS: Ca2+ currents were obtained in
      acutely dissociated mouse spermatogenic cells using whole-cell patch clamp
      technique and the effects of Flu on ICaT were observed. RESULTS: Flu of 0.1, 1,
      10, 100 micromol/L inhibited ICaT in mouse spermatogenic cells significantly with
      the K50 value of 0.289 micromol/L (P < 0.05). With the holding potential at -90
      mV and stimulating potential at -30 mV, the inhibition rates of Flu were (23.34
      +/- 2.76)%, (46.04 +/- 3.52)%, (62.52 +/- 3.70)% and (73.52 +/- 3.12)%,
      respectively. CONCLUSION: Flu has significant inhibitory effects on ICaT in mouse
      spermatogenic cells, with concentration dependence. Ca(v)3.2 is the main
      contributor to T-type Ca2+ currents in spermatogenic cells.

PMID- 16894934
TI  - [Effect of compound glycyrrhizin on peripheral T-lymphocyte subset in AIDS
      patients].
AB  - OBJECTIVE: To probe the effect and mechanism of Compound Glycyrrhizin in treating
      AIDS. METHODS: Forty AIDS patients were randomly divided into a treatment group
      and a control group, both treated with HAART. In addition, the former was given
      Compound Glycyrrhizin for 6 months, and the CD4+ T count and the expressions of
      CD8+ and HLA-DR on the surface of peripheral blood lymphocytes (PBL) were studied
      before and after the treatment. RESULTS: After 6 months of treatment, the
      expressions of CD8+ and CD38+ of PBL in the treatment group [(6.6 +/- 2.1)%] were
      found lower than in the control [(11.4 +/- 3.8)%] (t = 5.043, P < 0.01) and CD4+
      T count [(243.6 +/- 91.2) x 10(6)/L vs (170.8 +/- 55.7) x 10(6)/L] rose more
      significantly (t = 3.045, P < 0.01). CONCLUSION: Compound Glycyrrhizin can lower
      the expression of active T-lymphocyte subset, inhibit HIV and help immune
      reconstitution.

PMID- 16894935
TI  - [Antifertility effect of 30% ethanol retro-injection into rat vas deferens].
AB  - OBJECTIVE: To explore the antifertility effect and safety of 30% ethanol retro
      injection into the vas deferens of the rat. METHODS: Thirty Sprague-Dawley male
      rats, 3 m of age and (200 +/- 20) g in weight, were equally randomized into an
      experimental group and a control group. The former received 30% ethanol (0.5 ml)
      and the latter 0.9% sodium chloride (0.5 ml), both retro-injected into the vas
      deferens. Pregnancy rates were obtained through pregnancy tests with 60 Sprague
      Dawley female adult rats 1.5 m and 3 m after the injection. All the male rats
      were sacrificed three months later, and tests were done for the rates of sperm
      motility and deformity as well as for the apoptosis of spermatogenic cells with
      TUNEL. RESULTS: The 1.5 m pregnancy rate was 0 and the 3 m sperm motility and
      pregnancy rates were (0.32 +/- 1.12)% and (0.58 +/- 1.27)%, significantly
      decreased (P < 0.05) as compared with those of the control group, which were
      (80.62 +/- 2.68)%, (70.68 +/- 1.62)% and (86.62 +/- 1.68)%, respectively. While
      the 3 m sperm deformity rate in the experimental group was (78.26 +/- 1.08)%,
      increased significantly (P < 0.05), and the apoptosis index (AI) of spermatogenic
      cells was (7.63 +/- 1.16)% as compared with (5.62 +/- 1.32)% of the control
      group, with no significant difference between the two groups (P > 0.05).
      CONCLUSION: Retro-injection of 30% ethanol into the vas deferens of the rat
      produces significant antifertility effect on rats, but has no significant
      influence on their spermatogenic cells.

PMID- 16894936
TI  - [Relationships among human follicular fluid-induced acrosome reaction, sperm
      morphology and in vitro fertilization rates].
AB  - OBJECTIVE: To assess the relationships among human follicular fluid-induced
      acrosome reaction, sperm morphology and in vitro fertilization rates. METHODS:
      The relationships among human follicular fluid-induced acrosome reaction, sperm
      morphology and in vitro fertilization rates were investigated by Spearman rank
      correlation in 79 infertile couples. And the sperm morphology analysis was
      performed by crystal violet staining and based on strict criteria. RESULTS: A
      significant positive correlation was found between the percentage of human
      follicular fluid-induced acrosome reaction and that of normal sperm morphology (n
      = 49, r = 0.3763, P < 0.01), but no significant correlation was observed either
      between the percentage of human follicular fluid-induced acrosome reaction and in
      vitro fertilization rates or between that of normal sperm morphology and in vitro
      fertilization rates (n = 21, r = 0.2666, P > 0.05 and n = 50, r = 0.0018, P >
      0.05, respectively). CONCLUSION: There is a significant positive correlation
      between the percentage of human follicular fluid-induced acrosome reaction and
      that of normal sperm morphology, but no such correlation either between the
      percentage of human follicular fluid-induced acrosome reaction and in vitro
      fertilization rates or between that of normal sperm morphology and in vitro
      fertilization rates.

PMID- 16894937
TI  - [Application of flow cytometry to the evaluation of semen quality].
AB  - OBJECTIVE: To evaluate the role of flow cytometry in semen assessment. METHODS:
      Semen samples from 104 infertile male patients (as the case group) and 10
      fertilized donors (as the control group) were analyzed for the volume of
      ejaculate and sperm concentration, motility and atypical morphology by computer
      assisted semen analysis (CASA), the viability, chromatin structure and
      mitochondrial membrane potential (MMP) of the sperm stained by SYBR-14/PI, AO and
      JC-1 respectively, and assessed with flow cytometry. The results were analyzed
      through SAS software. RESULTS: U tests indicated that the semen from the
      infertile patients had not only lower concentration (U = 2.51, P = 0.0143), lower
      motility (U = 3.44, P = 0.001) and higher rate of atypical morphology (U = -5.88,
      P < 0.0001), but also lower viability (U = 4.72, P < 0.0001), MMP (U = -2.53, P =
      0.0309), and chromatin integrity (alpha t: U = -3.82, P = 0.0003; SD alpha t: U =
      -3.98, P = 0.0001; COMP alpha t: U = -3.57, P = 0.0005). The multiple stepwise
      regression analysis revealed that sperm motility was positively correlated with
      sperm membrane integrity (t = 1.66, P = 0.1016), sperm MMP (t = 3.33, P = 0.0014)
      and sperm acrosome integrity (t = 3.24, P = 0.0019), while sperm MMP was
      negatively correlated with the rates of sperm neck and tail defects (t = -3.44, P
      = 0.001). CONCLUSION: Flow cytometry plays a significant role in the evaluation
      of the quality of human sperm, and can be adopted as a useful tool in the
      diagnosis and treatment of male infertility.

PMID- 16894938
TI  - [Hypogonadism may cause insulin resistance in young males].
AB  - OBJECTIVE: To investigate the relationship between hypogonadism and insulin
      resistance in young male. METHODS: Twenty-one hypogonadism young males aged 15 to
      30 years were included in the clinical trial group, and 11 healthy young males of
      similar age and BMI in the control. Height, weight, serum FSH, LH, total
      testosterone (TT), nuclear type and bone age were measured for all the subjects.
      Serum glucose and insulin levels were taken through 3 h OGTT at 0, 30, 60, 120
      and 180 min. And comparisons were made of the levels of fast glucose and insulin,
      areas under the curve of glucose and insulin and HOMA insulin resistance indexes
      (HOMA-IR) between the two groups. RESULTS: (1) In the hypogonadism group the
      average value of TT was (0.9 +/- 0.6) nmol/L and 5 cases of Klinefelter syndrome
      had pubertal development with Tanner stage above P3, while the other 16 had no.
      (2) No significant differences were found in BMI, age, areas under the glucose
      and insulin secretory curve in OGTT between the two groups. (3) Three patients
      were diagnosed as IGT by OGTT in hypogonadism group, whose serum glucose levels
      at 120 min were 8.6, 7.9 and 8.2 mmol/L respectively. The maximal insulin
      excretion time was 30 min after glucose loading. No IGT or DM was found in the
      control group. (4) Significant difference was found in HOMA-IR and fast insulin
      level between the two groups. CONCLUSION: (1) IGT incidence was higher in the
      hypogonadism group than in the control. (2) HOMA-IR and fast insulin levels were
      significantly higher in the hypogonadism group than in the control, which
      suggests that lower serum testosterone may cause insulin resistance in young male
      patients.

PMID- 16894939
TI  - [Correlation of Ureaplasma urealyticum and Chlamydia trachomatis infections with
      male sterility: a meta-analysis of randomized control trials].
AB  - OBJECTIVE: To evaluate the correlation of Ureaplasma urealyticum (Uu) and
      Chlamydia trachomatis (Ct) infections with male sterility. METHODS: Data from
      CBMA and CNKI were searched and studies were made for the correlation of Uu and
      Ct infections with male sterility by retrieval strategy worked out according to
      the Collaborative Review Group search strategy. The results were expressed as
      odds ratio (OR) and 95% confidence intervals (95% CI). The results of 28 clinical
      controlled trials from 1994 to 2005 were analyzed by software RevMan 4.2. Odds
      ratio (OR) was applied to the evaluation of the correlation between Uu infection
      and male sterility. RESULTS: Eighty-eight relative trials were retrieved, of
      which 28 were included in the Meta-analysis. The combined ORs of Uu and Ct
      infections to male sterility were OR(Uu): 4.73 (95% CI: 3.77-5.94) and OR(Ct):
      4.59 (95% CI: 3.24-6.50). CONCLUSION: Uu and Ct infections are very important
      risk factors of sterility in Chinese men.

PMID- 16894940
TI  - [Effects of experimental varicocele on the apoptosis of epididymis epithelium and
      synthesizing function of the epididymis in rats].
AB  - OBJECTIVE: To study the relationships of experimental varicocele to the apoptosis
      of epididymis epithelium and changes of the contents of alpha-1,4-glucosidase and
      sialic acid from the unilateral epididymis in adolescent rats, and to investigate
      the effects of varicocele on the unilateral epididymis epithelium. METHODS:
      Experimental left varicocele models of 16 adult male Sprague-Dawley rats were
      obtained by partial ligation of the left renal vein. The epididymides were
      collected for detecting the apoptosis of epididymis epithelium and the contents
      of alpha-1,4-glucosidase and sialic acid by using spectrophotometry. RESULTS:
      Seven days after the establishment of the left varicocele model, the index of the
      apoptosis of the left epididymis epithelium was significantly higher (P < 0.001)
      and the contents of alpha-1,4-glucosidase and sialic acid significantly lower (P
      < 0.05, P < 0.005) in the experimental group than in the control. CONCLUSION: The
      results suggest that unilateral varicocele may increase the apoptosis of
      epididymis epithelium and the contents of alpha-1,4-glucosidase and sialic acid
      and subsequently affect the synthesizing and secretory function of the
      epididymis.

PMID- 16894941
TI  - [Surgical approaches to the correction of congenital penile curvature].
AB  - OBJECTIVE: To evaluate some currently used surgical approaches to the correction
      of congenital penile curvature. METHODS: Seventy-six patients with congenital
      penile curvature underwent surgical correction, of whom 67 were accompanied with
      hypospadias, 5 with epispadias and 4 with normal urethral meatus. The methods for
      straightening the phallus included 5-week preoperative hCG treatment, complete
      degloving of penile skin, release of periurethral fibrous bands extending
      proximally to the meatus, plication of dorsal or ventral tunica albuginea, and
      embedding of dermis and tunica vaginalis grafts. RESULTS: All the cases were
      followed up for 2 months to 2 years, and the mean follow-up time was 9.3 months.
      Satisfactory phallus straightening was achieved in 67 cases (88%), mild residual
      chordee remained in 6 (8%), which needed no reoperation for the time being unless
      warranted by follow-up, and relapse occurred in 3 (4%), which needed further
      operation. CONCLUSION: Most cases of congenital penile curvature can be corrected
      sufficiently with the above methods.

PMID- 16894942
TI  - [Application study of human sperm motility bioassay in IVF laboratory quality
      control].
AB  - OBJECTIVE: To investigate the sensitivity of human sperm survival bioassay to
      using known concentrations of potential toxin of formalin and to elevate the
      application value of human sperm motility assay as a quality control method in
      detecting the components used in IVF program. METHODS: Fresh semen was obtained
      from healthy males at andrology laboratory by masturbation. Sperm was processed
      on a gradient column of isolate medium and PBS medium. In experiment 1, the
      medium with 0.25%, 0.75% concentration of formalin and control medium were added
      to the Falcon culture tubes containing HTF medium with or without 0.3% bovine
      albumin serum and with or without light mineral oil. In experiment 2, in 3 types
      of culture tubes containing HTF medium with or without 0.3% bovine albumin serum
      and with or without light mineral oil, the sperm was exposed to each culture tube
      and cultured for 24 and 48 hrs at room temperature, and the motile sperms were
      counted under the microscope. RESULTS: The average sperm motility index in the
      HTF medium with 0.25% formalin at 24 hrs was 0.594 +/- 0.331, significantly
      higher than in the HTF medium with 0.75% formalin (0.450 +/- 0.284) (P < 0.01).
      In the medium containing 0.25% and 0.75% formalin with 0.3% bovine albumin serum
      and light mineral oil, the average sperm survival indexes were 0.683 +/- 0.334
      and 0.527 +/- 0.345, respectively, higher than without bovine albumin serum and
      light mineral oil (0.394 +/- 0.311 and 0.424 +/- 0.311). The average sperm index
      of 7 ml tissue culture tube made in Denmark was 0.677 +/- 0.335, higher than the
      other two types of culture tubes made in the USA (0.551 +/- 0.317 and 0.596 +/-
      0.327) (P < 0.001). When the sperm cultured in the medium with 0.3% bovine
      albumin serum and light mineral oil, the average sperm survival indexes were
      0.821 +/- 0.259 and 0.645 +/- 0.335, respectively, higher than without bovine
      albumin serum or light mineral oil (0.571 +/- 0.321 and 0.395 +/- 0.245) (P <
      0.01). CONCLUSION: The sperm survival bioassay is a sensitivity quality control
      method to detect the components in the IVF laboratory. The 7 ml tissue culture
      tube made in Denmark is most suitable for culturing human embryos. Sperm can be
      protected when cultured in the medium with 0.3% albumin bovine serum and light
      mineral oil.

PMID- 16894943
TI  - [BRG1 expression in prostate carcinoma by application of tissue microarray].
AB  - OBJECTIVE: To investigate the expression of gene BRG1 in prostatic
      intraepithelial neoplasia and adenocarcinoma, and the relationship between gene
      BRG1 expression and the clinicopathological features of prostate carcinoma.
      METHODS: Gene BRG1 expression was evaluated in 37 cases of human prostate
      carcinoma, 13 human prostatic intraepithelial neoplasia (PIN) and 14 human benign
      prostatic hyperplasia (BPH) by using immunohistochemistry (EnVision method) and
      tissue microarray. RESULTS: The positive rates of BRG1 protein were 81.08%
      (30/37), 38.46% (5/13) and 14.28% (2/14) in prostate carcinoma, PIN and BPH,
      respectively, significantly higher in the first group than in the latter two (P <
      0.05). There was no statistically significant difference in BRG1 gene expression
      either between PIN and BPH (P > 0.05) or between the groups of the moderate
      differentiation (the Gleason histologic grading: 5-7) and the lower one (the
      Gleason histologic grading: 8-10) (P > 0.05). CONCLUSION: BRG1 may play an
      important role in the development of prostate carcinoma. Tissue microarray
      technology, with the advantages of high throughput, conciseness, rapidity, high
      efficiency, low cost, and nice reproducibility, has significant practical value
      and broad application prospects in pathology.

PMID- 16894944
TI  - [Treatment of male adrenogenital syndrome (report of 17 cases)].
AB  - OBJECTIVE: To discuss the treatment of male adrenogenital syndrome. METHODS: The
      clinical data of 17 patients with male adrenogenital syndrome, including 15 cases
      of congenital adrenal hyperplasia (CAH) and 2 cases of adrenocortical tumors,
      were analyzed retrospectively. The patients with 21-hydroxylase deficiency (21
      OHD) and 11beta-hydroxylase deficiency (11beta-OHD) were treated with
      adrenocortical hormone, those with 17-hydroxylase deficiency (17-OHD) received
      sexual glands excision and estrogen besides adrenocortical hormone, and those
      with adrenocortical tumors underwent surgical removal. RESULTS: Sexual precocity
      symptoms disappeared and abnormal laboratory results returned to normal in 5 of
      the 21-OHD patients, who adhered to hormone treatment, and height growth was
      improved in the other 2, who received the medicine at an early age. The
      testicular adrenal rest (TAR) tumor was reduced dramatically in 1 case of 21-OHD
      after treatment. A left TAR found in another 21-OHD patient who discontinued the
      hormone therapy became softened after the resumption. Sperm could be seen in the
      semen of 3 21-OHD patients, but in small quantity and of poor quality. One 11beta
      OHD patient with sexual precocity symptoms and hypertension became normal after
      the hormone treatment, and six 17-OHD patients maintained their female sexuality
      after the hormone treatment and operation. No relapse was found after resection
      of the adrenocortical tumors. CONCLUSION: Adrenocortical hormone therapy helps
      improve the height growth and testicular function of CAH patients, and surgical
      removal is necessary for adrenocortical tumors.

PMID- 16894945
TI  - [Apoptosis of epididymal epithelium and the content of epididymal carnitine
      following testicular torsion/detorsion in rats].
AB  - OBJECTIVE: To investigate the relationship between the apoptosis of epididymal
      epithelium and the change of epididymal carnitine following testicular
      torsion/detorsion in rats. METHODS: Twenty-four healthy adult male Sprague-Dawley
      rats were randomly divided into 3 groups: Group A (2-hr torsion), Group B (5-hr
      torsion) and a control group (0-hr torsion). The ipsilateral epididymides were
      collected for detecting the content of carnitine by DTNB technique and the
      apoptosis of epididymal epithelium by TUNEL technique. RESULTS: Twenty-four hours
      after the treatment, there was no statistically significant difference in the
      apoptosis of epididymal epithelium and the content of epididymal carnitine
      between the 2-hr torsion/detorsion group and the control (P > 0.05). However,
      there was statistically significant difference in the apoptosis of epididymal
      epithelium and the content of epididymal carnitine between the 5-hr group and the
      control (P < 0.05). CONCLUSION: Twenty-four hours after 2-hr testicular
      torsion/detorsion, the carnitine-concentrating function of the epididymis may
      remain normal and the apoptosis index of epididymal epithelium does not increase
      significantly, while one day after 5-hr testicular torsion/detorsion, the
      apoptosis index increases and the carnitine-concentrating function decreases.

PMID- 16894946
TI  - [Damage to and protection of sperm DNA].
AB  - The damage to sperm DNA is one of the most important causes of male infertility.
      Some sperm with damaged DNA may escape from the sperm surveillance mechanism and
      transmit the damage to the offspring. So research on the damage to sperm DNA has
      become one of the hot spots in reproductive medicine. The factors that would
      damage sperm DNA include oxidative stress, microelements, reproductive toxic
      substances, radioactive rays, and so on, while the body depends on the compressed
      sperm DNA and anti-oxidation system for the protection of the integrity of sperm
      DNA. Some drugs such as anti-oxidant, black tea extract, etc, may help to improve
      and rebuild these protective mechanisms.

PMID- 16894947
TI  - [Hyperlipidemia and erectile dysfunction].
AB  - Hyperlipidemia is one of the risk factors leading to erectile dysfunction (ED), a
      common disorder in men, especially in old men. Epidemiological studies have found
      that the decrease in high density lipoprotein (HDL) and elevation of total
      cholesterol/high density lipoprotein (TC/HDL) are correlated with ED. Studies
      have also shown that arterial stenosis and occlusion caused by hyperlipidemia
      could be attributed to the advanced-stage mechanism of ED induced by
      hyperlipidemia. Hyperlipidemia may damage man's erectile function at an early
      stage by affecting the endothelial cells and smooth muscles of the penis and the
      peripheral nerves for penile erection. Apart from dietary therapy and drug
      therapy aiming at hyperlipidemia, the traditional Chinese medicine therapy and
      gene therapy are two promising approaches to the treatment of ED caused by
      hyperlipidemia.

PMID- 16894948
TI  - [Advances in the studies of Kallmann syndrome].
AB  - Kallmann syndrome (KS) is a rare hereditary disease. It is characterized by
      hypogonadotrophic hypogonadism in association with anosmia or hyposmia. At
      present, three modes of inheritance and genes related to KS have been identified.
      This review focuses on the clinical diagnosis and advances in the studies of the
      pathogenesis gene for Kallmann syndrome.

PMID- 16894949
TI  - [A list and analysis of reproductive medicine periodicals indexed in MEDLINE in
      2006].
AB  - MEDLINE established by National Library of Medicine (NLM), USA, is the most
      commonly used biomedical literature retrieval system, whose indexed literature
      generally represents the top of the medical world. Of the total number of 4959
      journals listed in the Lists of Journals Indexed in MEDLINE (2006) published by
      NLM, 46 are periodicals of reproductive medicine, mainly including andrology,
      fertility, and sterility. Researchers of reproductive medicine should be familiar
      with the journals indexed in MEDLINE, closely follow their published frontier
      researches in this field, and consciously contribute to them in English. Editors
      of reproductive medicine journals should endeavour to have their journals
      included in such internationally authoritative systems as MEDLINE, SCI, etc by
      publishing them in English in compliance with international standards. This
      article presents a list of the reproductive medicine periodicals indexed in
      MEDLINE (2006) together with a brief analysis, which is meant to help researchers
      in reproductive medicine, andrology and other relevant fields with their
      contribution, subscription, reading and retrieving, as well as to share some more
      knowledge about MEDLINE and its indexed journals with Chinese editors of
      reproductive medicine journals.

PMID- 16894950
TI  - [Reliable efficacy of vardenafil for treatment of erectile dysfunction].
AB  - Reliable efficacy is very important to continuing treatment for patients with
      erectile dysfunction. Vardenafil is a potent, highly selective phosphodiesterase
      5 (PDE5) inhibitor. The efficacy and safety of vardenafil has been confirmed in
      many clinical studies. This paper analyzed the efficacy reliability of vardenafil
      in clinical trials and real-life practice, concluded that it provided reliable
      efficacy for key parameters of erection and improved treatment compliance.

PMID- 16894951
TI  - [Death, death always happens anew].

PMID- 16894953
TI  - [Management of unresectable non-metastatic non-small cell lung cancer. Guidelines
      of clinical practice made by the European Lung Cancer Working Party].
AB  - The present guidelines on the management of unresectable non-metastatic non-small
      cell lung cancer (NSCLC) were formulated by the ELCWP in October 2005. They are
      designed to answer the following eight questions: 1) Is chest irradiation
      curative for NSCLC? 2) What are the contraindications (anatomical or functional)
      to chest irradiation? 3) Does the addition of chemotherapy add any advantage to
      radiotherapy? 4) Does the addition of radiotherapy add any advantage to
      chemotherapy? 5) In marginally respectable stage III is irradiation as effective
      as surgery? 6) How to best combine chemotherapy with radiotherapy: sequentially,
      concomitantly, as consolidation, as induction, as radiosensitiser? 7) In case of
      too advanced locoregional disease, is there a role for consolidation (salvage)
      local treatment (surgery, radiotherapy) after induction chemotherapy? 8) In 2005,
      what are the technical characteristics of an adequate radiotherapy?

PMID- 16894952
TI  - [The Cancer Registry of the Jules Bordet Institute, a new tool for the
      institution and its researchers. Description of cases incident in 2000-2001].
AB  - A hospital Cancer Registry has recently been initiated at the Jules Bordet
      Institute. The collected information allows to report pathology items such as
      incidence date, site, morphology and stage. It permits to describe the
      therapeutic choices, which, broken down by organ and stage, can be compared to
      guidelines in a process assessment. The objectives of this registry are
      institutional (statistical and organisational finalities as well as quality
      control ones), extra-institutional (participation to the public network of cancer
      registration), and scientific (providing the researchers a common database that
      can be queried using multiple criteria to be completed by further detailed data).
      This paper reports on 3,587 incident cancer cases in 2000 and 2001 which were
      managed at the Jules Bordet Institute for the primary episode. Cancers in women
      represent 64.3% of all records, for only 35.7% of men, while in the Belgian
      National Cancer Registry, the proportion is reversed to 46.7% of women and 53.3%
      of men. The distribution of cancer by site is also quite different in our
      hospital registry where breast cancer in women, melanoma in both sexes, lung
      cancer and head and neck cancers in men are over-represented compared to the
      general population, while colorectal cancer is underrepresented in both sexes.

PMID- 16894954
TI  - [Goodpasture disease].
AB  - We report one case of acute renal failure with oliguria, microscopic haematuria
      and normocytic anemia in a 86-year old Swedish woman. A full investigation led to
      the diagnosis of Goodpasture disease, an isolated form of Goodpasture syndrome.
      Goodpasture disease is and autoimmune disorder characterized by the development
      of autoantibodies to the NC1 domain of the alpha3 chain of type IV collagen,
      found mainly in glomerular basement membranes (GBM). When the disease affects
      both the lung and the kidney, it is called Goodpasture syndrome but the pulmonary
      or renal involvement can be isolated or separated in years. Its pathogenesis is
      not well known. It occurs essentially in Caucasian subjects, preferentially from
      Nordic and Anglo-Saxon countries (higher prevalence of HLA DR B1-15 and B1-4
      group). Are also mentioned, the exposure to hydrocarbons, rustproof, insecticides
      and greasy solvents. The annual incidence of Goodpasture syndrome is rare and has
      been estimated in Europe to be about 0.5 to 1 case per million inhabitants. The
      isolated renal form represents about 1/3 of the cases. The clinical presentation
      is characterized by rapidly progressive renal failure with oliguria or anuria and
      in case of lung involvement, pulmonary hemorrhage responsible of hemoptysis,
      sometimes massive. Renal biopsy and immunofluorescence analysis play a key role
      in the diagnosis. The presence of both linear deposits of IgG along the
      glomerular basement membrane (GBM) and circulating anti-GBM antibodies is of
      paramount importance. The treatment, which depends on the degree of renal
      involvement, is based on the association of corticosteroids, cyclophosphamide and
      plasma exchanges.

PMID- 16894955
TI  - [Omalizumab, an anti-IgE monoclonal antibody to treat severe asthma].
AB  - Omalizumab (Xolair) is the first representative of a new therapeutical class,
      which will be soon available in severe allergic asthma. By neutralizing Ac IgE,
      omalizumab fulfils an anti-inflammatory action of which the effect has been shown
      beneficial in the treatment of severe allergic asthma and particularly in severe
      asthma for which the therapeutical arsenal is for the time being disappointing
      and associated to frequent side effects there where omalizumab is well tolerated.

PMID- 16894957
TI  - [Misdiagnosis of sinus thrombosis with reversible posterior leucoencephalopathy].
AB  - Reversible posterior leucoencephalopathy and cerebral venous thrombosis share
      many symptoms. Both of them may lead to coma, and cause epilepsy or focal
      neurological signs. Moreover, diffuse leucoencephalopathy can be observed in both
      cases. Cerebral venous thrombosis needs anticoagulation which is not a riskless
      treatment. We describe a case of reversible posterior leucoencephalopathy in an
      hypertensed, seventy-year old man, presenting with a left lateral sinus
      hypoplasia whose clinical history and paramedical results first suggested a
      cerebral veinous thrombosis. Our case shows the misleadings a congenital vascular
      asymmetry can induce when confronted with a subacute coma.

PMID- 16894956
TI  - [Everyday questions in laboratory medicine].
AB  - Until the sixties, it was usual for a MD to make some lab tests in a room close
      to his medical office. During the next decades, the number of lab tests has
      exploded, and the performance of the test became dissociated from the MD ordering
      the tests. All Belgian clinical laboratories are involved in the management of a
      quality system, and within it, the general practitioner is essential as partner.
      Good communication with him/her may put in evidence inadequacies in some
      processes such as the performance of the tests or the transmission of the reports
      to the ordering MD. The requirement for a good contact between the ordering MD
      and the clinical pathologist is described in some cases of everyday work in
      laboratory medicine: screening for thyroid dysfunction; indications of total PSA
      and free PSA; screening for hemochromatosis; prothrombin time and INR; serology
      tests for infectious mononucleosis or syphilis.

PMID- 16894958
TI  - [Therapy of an odontoid fracture].

PMID- 16894959
TI  - [Seventh annual meeting of thoracic oncology].

PMID- 16894960
TI  - [Jules Bordet Institute: past, present and future].
AB  - Since the end of the 19th century, the Universite Libre de Bruxelles and the
      Conseil des Hospices, in charge of health problems in the city of Brussels,
      assume the responsibility of cancer patients. A first cancer clinic is organized
      in 1906 followed in 1925 by the building of a cancer pavilion on the site of the
      Hopital Brugmann. In 1935 the building of a new more important cancer institute
      is decided by the Commission d'Assistance Publique and the Universite Libre de
      Bruxelles. The Institut Bordet was inaugurated in 1939. In 1950, the appointment
      of Albert Claude, future Nobel Prize, as scientific director of the Institute
      inaugurated a period of important and growing medical and scientific activities.
      The Institute became a multidisciplinary center with medical departments
      (clinical biology, medicine, pathology, radiodiagnosis, radiotherapy, surgery)
      and investigation laboratories. There is a project to build a new Institute on
      the campus of the Hopital Erasme.

PMID- 16894961
TI  - An agglutinin with mitogenic and antiproliferative activities from the mushroom
      Flammulina velutipes.
AB  - A hemagglutinin with a molecular mass of 12 kDa was isolated from the fruiting
      bodies of the mushroom Flammulina velutipes. Its molecular mass is similar to
      that of the fungal immunomodulatory protein isolated from F. velutipes (FIP-fve)
      with ice-cold 5% acetic acid and 50 mM 2-mercaptoethanol as extraction medium and
      to that of the larger 12 kDa subunit of F. velutipes lectin isolated with
      phosphate buffer as extraction medium. Its hemagglutinating activity cannot be
      inhibited by a variety of carbohydrates tested. The activity is stable between pH
      4 and pH 11. Loss in activity occurred when the temperature is raised to 60 C and
      70 C. Activity is indiscernible at and above 80 C. Its N-terminal sequence shows
      differences from that of FIP-fve. F. velutipes hemagglutinin stimulates [3H
      methyl] thymidine uptake by mouse splenocytes. It inhibits proliferation of
      leukemia L1210 cells with an IC50 of 13 microM.

PMID- 16894962
TI  - Fungal decomposition of Abies needle and Betula leaf litter.
AB  - The effect of litter type and incubation temperature on the ability of fungi to
      decompose leaf litter of subalpine trees was examined by a pure-culture test.
      Mass loss of Abies needle and Betula leaf litter and utilization patterns of
      lignin and carbohydrates were investigated under two temperature conditions (20 C
      and 10 C) and compared for 29 species in basidiomycetes, ascomycetes and
      zygomycetes. The decomposing ability was generally higher in basidiomycetes than
      in ascomycetes and zygomycetes. Mass loss (% original mass) of litter was higher
      in Betula than in Abies and higher at 20 C than at 10 C. The 29 fungi were
      divided into lignocellulose decomposers, cellulose decomposers and sugar fungi
      based on their substrate utilization in Abies and Betula litter. Mass loss of
      lignin and carbohydrates by lignocellulose and cellulose decomposers was higher
      in Betula than in Abies. Mass loss of carbohydrates was higher at 20 C than at 10
      C, but the temperature did not influence mass loss of lignin, indicating lignin
      decomposition by fungi was less sensitive to temperature than carbohydrate
      decomposition. Lignin/carbohydrate loss ratio (L/C) of Collybia spp. that caused
      selective delignification was lower at 20 C than at 10 C. These results indicate
      that the decomposability of litter, lignin and carbohydrate was different between
      Abies and Betula and that temperature affected not only the rate at which fungi
      decompose litter but also the ability of fungi to use lignin and carbohydrates.

PMID- 16894963
TI  - A bioactive (1-->3)-, (1--4)-beta-D-glucan from Collybia dryophila and other
      mushrooms.
AB  - Polysaccharides from higher Basidiomycete mushrooms, mainly beta-D-glucans, are
      considered to be potent bioactive fungal compounds. In this study a beta-glucan
      (1.237 x 10(6) Da) consisting of (1-->3) and (1-->4) glucosidic linkages, named
      Collybia dryophila polysaccharide (CDP), was extracted from the wild mushroom C.
      dryophila. CDP was shown to strongly inhibit nitric oxide production in activated
      macrophages suggesting that this polysaccharide displays a potential anti
      inflammatory activity. In addition it was shown that polysaccharides similar to
      CDP (CDP-like) are present in Lentinus edodes and different wild mushrooms
      collected in northeastern North America.

PMID- 16894964
TI  - Generality of the prerequisite of conidium attachment to a hydrophobic substratum
      as a signal for germination among Phyllosticta species.
AB  - It has been shown that conidia of Phyllosticta ampelicida require attachment to a
      substratum to initiate germination. Furthermore this attachment occurs only on
      hydrophobic surfaces. This study was initiated to ascertain the breadth of this
      phenomenon among other species of the genus Phyllosticta. We tested 23 isolates
      of Phyllosticta representing at least 14 named species. These isolates were
      collected from North America, Asia and Africa. For 22 of the 23 isolates tested
      spore attachment occurred at a rate of 60-100% on hydrophobic polystyrene but at
      0-5% on hydrophilic polystyrene. The one exception to the preference for a
      hydrophobic substratum for attachment was an unnamed species of Phyllosticta from
      Rhus glauca that attached less than 10% on either surface. A similar response was
      observed when assaying germination and appressorium formation for 17 isolates.
      Germination and appressorium formation for these isolates proceeded on
      hydrophobic polystyrene but not on nutrient agar, which is hydrophilic. In five
      of the tested isolates germination was high on both hydrophobic polystyrene and
      hydrophilic nutrient media. The isolate from Rhus glauca did not germinate
      appreciably on either surface. Taken together these results suggest that the
      requirement for conidium contact/attachment to trigger germination is pervasive
      to the genus Phyllosticta.

PMID- 16894965
TI  - Species diversity of polyporoid and corticioid fungi in northern hardwood forests
      with differing management histories.
AB  - Effects of forest management on fungal diversity were investigated by sampling
      fruit bodies of polyporoid and corticioid fungi in forest stands that have
      different management histories. Fruit bodies were sampled in 15 northern hardwood
      stands in northern Wisconsin and the upper peninsula of Michigan. Sampling was
      conducted in five old-growth stands, five uneven-age stands, three even-age
      unthinned stands and two even-age thinned stands. Plots 100 m x 60 m were
      established and 3000 m2 within each plot was sampled during the summers of 1996
      and 1997. A total of 255 polyporoid and corticioid morphological species were
      identified, 46 (18%) of which could not be assigned to a described species.
      Species accumulation curves for sites and management classes differed from
      straight lines, although variability from year to year suggests that more than 2
      y of sampling are needed to characterize annual variation. Mean species richness
      and diversity index values did not vary significantly by management class,
      although mean richness on large diameter wood (> or = 15 cm diam) varied with
      moderate significance. Richness values on small diameter debris varied
      significantly by year, indicating that a large part of year-to-year variability
      in total species richness is due to small diameter debris. Ten species had
      abundance levels that varied by management class. Two of these species. Changes
      in the diversity and species composition of the wood-inhabiting fungal community
      could have significant implications for the diversity, health and productivity of
      forest ecosystems.

PMID- 16894966
TI  - Protostelids from tropical forests, woodlands and deserts in Australia.
AB  - Most of what is known about the distribution of protostelids is limited to
      results from surveys carried out in North and Central America. To increase our
      knowledge about protostelid diversity and distribution we surveyed protostelids
      from 12 study sites in northern Queensland and the Northern Territory of
      Australia during May-Jun 2003. Aerial litter and ground litter samples were
      randomly collected along a 200 m transect at each site. Study sites ranged from
      tropical forests to deserts. We recovered 10 species and two apparently
      undescribed species from samples of aerial (dead but still attached plant parts)
      and ground litter. Samples from a woodland site characterized by intermediate
      moisture conditions had the greatest species richness, followed by samples from
      dry woodland, tropical forest and desert sites. When species richness for a
      particular microhabitat was considered, samples of aerial litter yielded more
      species than samples of ground litter. Percentages of samples colonized with
      protostelids were similar for the aerial and ground litter microhabitats within a
      given habitat type except for dry woodlands, in which aerial litter samples were
      characterized by higher numbers of species than ground litter samples. Two
      species (Protostelium mycophaga and Soliformovum irregularis) that in temperate
      North America are associated with aerial litter microhabitats also were recovered
      from aerial litter in dry habitats in Australia. Schizoplasmodiopsis
      pseudoendospora, a North American temperate ground litter species, was equally
      abundant in aerial litter and ground litter in Australia. This study is the first
      of its kind for protostelid ecology in Australia and the most extensive study of
      protostelids in the southern hemisphere. These data complement ongoing research
      on protostelid distribution from around the world.

PMID- 16894967
TI  - Species richness and ecological characterization of myxomycetes and myxomycete
      like organisms in the canopy of a temperate deciduous forest.
AB  - The ecological community of myxomycetes and myxomycete-like organisms (MMLO) in
      the canopy of living deciduous trees was studied in a riparian deciduous forest
      at Leipzig, Germany. A systematic survey carried out with a total of 146 moist
      chamber cultures resulted in 386 records of 37 taxa, with 32 myxomycetes, two
      myxobacteria, two protostelids and the fruit body forming ciliate Sorogena
      stoianovitchae, the latter recorded for the first time for Europe. With 94% of
      all cultures positive for MMLO, these organisms are present consistently in the
      investigated sections of white-rotten twigs attached to living trees at 10-30 m
      above the ground. Our sampling recovered a majority of the likely species, with
      37 out of the 42-45 predicted according to a species-accumulation curve and two
      other estimators of species richness. Nonmetric multidimensional scaling revealed
      pH, water-holding capacity and stage of decay to explain most of the variation in
      species distribution. Arcyria cinerea and Perichaena depressa as the most common
      species occurred in 32% and 29% of all samples, respectively. Viewing the sampled
      twigs as habitat islands and a single spore as sufficient to establish a
      population, a simulation program assuming a random spore rain estimated an
      average of 0.4 and 0.35 spore hits per twig as necessary to explain the observed
      frequencies. This is matched by the potential productivity of the substrate. All
      fruit bodies from the cultured twigs would be able to create a spore rain of 86
      (A. cinerea) or 40 (P. depressa) spore hits per twig when dispersed evenly over
      the plot. The terminal fall velocity of spores was measured, revealing that it
      took about 5 h for a spore to land (30 m) in still air and indicating high
      dispersal ability for canopy-inhabiting MMLO.

PMID- 16894968
TI  - The number of nuclei in basidiospores of 63 species of ectomycorrhizal
      Homobasidiomycetes.
AB  - The production of even a limited number of heterokaryotic spores would be
      advantageous for establishing new individuals after long distance dispersal.
      While Suillus and Laccaria species are known to produce binucleate,
      heterokaryotic spores, this condition is poorly studied for most ectomycorrhizal
      fungi. To begin addressing this matter the number of nuclei in basidiospores was
      recorded from 142 sporocarps in 63 species and 20 genera of ectomycorrhizal (EM)
      fungi. The mean proportion of binucleate basidiospores produced by sporocarps
      within a species ranged from 0.00 to 1.00, with most genera within a family
      showing similar patterns. Basidiospores from fungi in Amanita, Cortinariaceae and
      Laccaria were primarily binucleate but were likely still homokaryotic.
      Basidiospores from fungi in Boletaceae, Cantharellus, Rhizopogonaceae,
      Russulaceae, Thelephorales and Tricholoma were primarily uninucleate, but
      binucleate basidiospores were observed in many genera and in high levels in
      Boletus. Further research is needed to relate basidiospore nuclear number to
      reproductive potential in ectomycorrhizal species.

PMID- 16894970
TI  - Spatial analysis of within-population microsatellite variability reveals
      restricted gene flow in the Pacific golden chanterelle (Cantharellus formosus).
AB  - We examined the within-population genetic structure of the Pacific golden
      chanterelle (Cantharellus formosus) in a 50 y old forest stand dominated by
      Douglas-fir (Pseudotsuga menziesii) and western hemlock (Tsuga heterophylla) with
      spatial autocorrelation analysis. We tested the null hypothesis that multilocus
      genotypes possessed by chanterelle genets were randomly distributed within the
      study area. Fruit bodies from 203 C. formosus genets were collected from a 50 ha
      study plot. One hundred six unique multilocus genotypes were identified after
      scoring these collections at five microsatellite loci. Statistically significant
      positive spatial autocorrelation was detected indicating the presence of fine
      scale genetic structure within the area. Repeated autocorrelation analyses with
      varied minimum distance classes (50-500 m) detected positive spatial genetic
      structure up to 400 m. Therefore nonrandom evolutionary processes (e.g.,
      isolation by distance) can cause fine-scale genetic structure in C. formosus. The
      implications of this research for future broad-scale population studies of this
      species are that population samples should be separated by at least 400 m to be
      considered statistically independent. Sampling designs that account for fine
      scale genetic structure will better characterize heterogeneity distributed across
      the landscape by avoiding the effects of pseudo replication.

PMID- 16894969
TI  - Cryphonectriaceae (Diaporthales), a new family including Cryphonectria,
      Chrysoporthe, Endothia and allied genera.
AB  - Recent phylogenetic studies on the members of the Diaporthales have shown that
      the order includes a number of distinct phylogenetic groups. These groups
      represent the Gnomoniaceae, Melanconidaceae, Valsaceae, Diaporthaceae and
      Togniniaceae. New groups representing undescribed families also have emerged and
      they have been referred to as the Schizoparme, Cryphonectria-Endothia and
      Harknessia complexes. In this study we define the new family Cryphonectriaceae
      (Diaporthales) to accommodate genera in the Cryphonectria-Endothia complex. These
      genera can be distinguished from those in other families or undescribed groups of
      the Diaporthales by the formation of orange stromatic tissue at some stage of
      their life cycle and a purple reaction in KOH and a yellow reaction in lactic
      acid associated with pigments in the stromatic tissue or in culture.

PMID- 16894971
TI  - Migration in Dictyostelium polycephalum.
AB  - By comparing two species of cellular slime molds that have stalkless migration
      stages it is possible to gain interesting insights into how the cells move. In
      contrast to the familiar behavior of Dictyostelium discoideum, Dictyostelium
      polycephalum slugs can travel greater distances through soil and even can migrate
      through agar. In addition to the interest in the differences, these differences
      shed light on the mechanism of slug movement. Unlike D. discoideum, D.
      polycephalum does not have prestalk and prespore zones and severed sections of
      any part of these slugs move at a rate proportional to their length. This leads
      to the hypothesis that longer slugs move faster because the amoebae aligned along
      the inside of the slime sheath each contribute a forward push and the more
      extended the amoebae line is the faster the slug moves.

PMID- 16894972
TI  - Phellinus caribaeo-quercicolus sp. nov., parasitic on Quercus cubana: taxonomy
      and preliminary phylogenetic relationships.
AB  - Phellinus caribaeo-quercicolus sp. nov. is described from several collections
      made in western Cuba, so far exclusively on Quercus cubana. The species is
      characterized by a perennial, resupinate basidiomes, cushion-shaped to nodulose
      and multi-layered when old, apically hooked to hamate hymenial setae, and
      ellipsoid to broadly ellipsoid, thin- to thick-walled, hyaline to faintly
      yellowish basidiospores, 4.5-5.5 x 3.5-4.5 microm. The species is compared to
      other Phellinus species with hooked setae, especially Phellinus undulatus, also
      recorded in Cuba. The preliminary phylogenetic relationships of Ph. caribaeo
      quercicolus within the poroid Hymenochaetales complex of genera is presented and
      discussed here.

PMID- 16894974
TI  - Acaulospora alpina, a new arbuscular mycorrhizal fungal species characteristic
      for high mountainous and alpine regions of the Swiss Alps.
AB  - Acaulospora alpina sp. nov. forms small (65-85 microm diam), dark yellow to
      orange-brown spores laterally on the neck of hyaline to subhyaline sporiferous
      saccules. The spores have a three-layered outer spore wall, a bi-layered middle
      wall and a three-layered inner wall. The surface of the second layer of the outer
      spore wall is ornamented, having regular, circular pits (1.5-2 microm diam) that
      are as deep as wide and truncated conical. A "beaded" wall layer as found in most
      other Acaulospora spp. is lacking. The spore morphology of A. alpina resembles
      that of A. paulinae but can be differentiated easily by the unique ornamentation
      with the characteristic pits and by the spore color. A key is presented
      summarizing the morphological differences among Acaulospora species with an
      ornamented outer spore wall. Partial DNA sequences of the ITS1, 5.8S subunit and
      ITS2 regions of ribosomal DNA show that A. alpina and A. paulinae are not closely
      related. Acaulospora lacunosa, which has similar color but has generally bigger
      spores, also has distinct rDNA sequences. Acaulospora alpina is a characteristic
      member of the arbuscular mycorrhizal fungal communities in soils with pH 3.5-6.5
      in grasslands of the Swiss Alps at altitudes between 1800 and 2700 m above sea
      level. It is less frequent at 1300-1800 m above sea level, and it so far has not
      been found in the Alps below 1300 m or in the lowlands of Switzerland.

PMID- 16894975
TI  - Aspergillus ibericus: a new species of section Nigri isolated from grapes.
AB  - As part of a study on the ochratoxin producing mycoflora of grapes, several
      Aspergillus strains were isolated and tested for their ochratoxin A (OTA)
      producing abilities. Aspergillus strains of the section Nigri, which did not
      produce detectable amounts of OTA but which had a similar morphology to A.
      carbonarius, were isolated from wine grapes and/or dried vine fruit in Portugal
      and Spain. These strains, however, have characters that allow morphological
      distinction from the other species in the section, particularly the conidia size
      (5-7 microm), which allows separation of the species from the two most common
      biseriate species in section Nigri: A. carbonarius (7-9 microm) and A. niger and
      its aggregate species (3-5 microm). The strains are described here as belonging
      to a new species, named A. ibericus. The validation of this new taxon is
      supported further by analysis of the ITS-5.8S rDNA and calmodulin gene sequences
      and by analysis of the amplified fragment length polymorphism (AFLP) patterns,
      which were consistent in separating these strains from other species in the
      section. A. ibericus strains do not produce OTA therefore they are interesting
      for biotechnological exploration because many metabolites with commercial value
      are produced by other species in the section.

PMID- 16894976
TI  - Two new species of Pseudogymnoascus with Geomyces anamorphs and their
      phylogenetic relationship with Gymnostellatospora.
AB  - Two new psychrophilic Pseudogymnoascus species with Geomyces anamorphs are
      described from a Sphagnum bog in Alberta, Canada. Pseudogymnoascus appendiculatus
      has long, branched, orange appendages and smooth, fusoid to ellipsoidal
      ascospores with a faint longitudinal rim. Pseudogymnoascus verrucosus has short,
      subhyaline appendages and warty peridial hyphae and ascospores, and both smooth
      to asperulate and irregularly warty conidia. Both species produce asci in chains,
      a feature that supports the distinction between this group and Myxotrichum, which
      produces asci singly. The discovery of species intermediate between
      Pseudogymnoascus and Gymnostellatospora, in having both ornamented ascospores and
      Geomyces anamorphs, prompted a re-evaluation of the genera. Sequence analysis of
      the internal transcribed spacer regions (ITS) of the nuclear ribosomal DNA
      indicates that the two genera remain distinct and comprise a monophyletic group.
      Pseudogymnoascus species have smooth to warty or lobate-reticulate ascospores
      while species of Gymnostellatospora have walnut-shaped spores with distinct
      longitudinal crests and striations. Anamorphs assignable to the form genus
      Geomyces are allied with both genera. A key is provided to the four species and
      varieties of Pseudogymnoascus.

PMID- 16894978
TI  - Trichomycete insect symbionts in Great Smoky Mountains National Park and
      vicinity.
AB  - Collections of trichomycete symbionts of larval aquatic insects in Great Smoky
      Mountains National Park and vicinity in the southern Appalachian region of the
      USA resulted in finding many taxa of Harpellales, including an unusual new
      monotypic genus, Barbatospora ambicaudata in Simuliidae, and five new species in
      Thaumaleidae or Chironomidae, Harpellomyces montanus, Smittium lentaquaticum, Sm.
      minutisporum, Stachylina gravicaudata and St. stenospora. In addition a new
      species of Amoebidium (Amoebidiales), A. appalachense, attached to the anal
      tubules of bloodworms (Chironomidae) is described. Axenic cultures of three of
      the new taxa were obtained, plus Sm. culisetae. Fourteen identified species
      representing 13 genera of previously known Harpellales are recorded from
      Plecoptera, Ephemeroptera and Diptera, as well as a new Dipteran host record for
      an unidentified harpellid that was found in a Blephariceridae. Also identified
      were Paramoebidium corpulentum and many undetermined species of Paramoebidium
      (Amoebidiales) from four orders of aquatic insect larvae. The occurrence of an
      Enterobryus species in Diplopoda and another Eccrinales from an aquatic beetle is
      noted. Amoebidiales,

PMID- 16894977
TI  - Jahnula species from North and Central America, including three new species.
AB  - Three new species of loculoascomycetes collected from freshwater habitats in
      North America are described as new species of Jahnula (Jahnulales,
      Dothideomycetes). All three share these morphological features: hyaline to
      blackish translucent, membranous ascomata with subtending, wide, septate brown,
      spreading hyphae; peridia composed of large angular cells; hamathecium of septate
      pseudoparaphyses; 8-spored, clavate to cylindrical asci; and 1-septate, broadly
      fusiform, brown, multiguttulate ascospores. Four additional species, J. aquatica,
      J. bipolaris, J. potamophila, and J. seychellensis, are reported for the first
      time from the western hemisphere.

PMID- 16894973
TI  - Host range of Cercospora apii and C. beticola and description of C. apiicola, a
      novel species from celery.
AB  - The genus Cercospora is one of the largest and most heterogeneous genera of
      hyphomycetes. Cercospora species are distributed worldwide and cause Cercospora
      leaf spot on most of the major plant families. Numerous species described from
      diverse hosts and locations are morphologically indistinguishable from C. apii
      and subsequently are referred to as C. apii sensu lato. The importance and
      ecological role that different hosts play in taxon delimitation and recognition
      within this complex remains unclear. It has been shown that Cercospora leaf spot
      on celery and sugar beet are caused respectively by C. apii and C. beticola, both
      of which are part of the C. apii complex. During this study we characterized a
      new Cercospora species, C. apiicola, which was isolated from celery in Venezuela,
      Korea and Greece. The phylogenetic relationship between C. apiicola and other
      closely related Cercospora species was studied with five different gene areas.
      These analyses revealed that the C. apiicola isolates cluster together in a well
      defined clade. Both C. apii and C. beticola sensu stricto form well defined
      clades and are shown to have wider host ranges and to represent distinct species.

PMID- 16894980
TI  - Integration of chemical engineering, environmental engineering, and
      bioengineering to facilitate research and education in nanotechnology,
      biotechnology, and sustainability.

PMID- 16894979
TI  - A microtiter plate procedure for evaluating fungal functional diversity on
      nitrogen substrates.
AB  - Ascertaining the effects of anthropogenic disturbance on belowground diversity is
      of paramount importance because pollution from agricultural practices and
      industrialization are increasing worldwide. Although we have methods for
      evaluating soil microbial function with respect to carbon use our ability to
      evaluate use of other compounds is limited. Because N cycling is of paramount
      importance in ecosystem stability, evaluation of the ability of saprophytic soil
      fungi to use a variety of N sources would provide important information on
      possible alterations in ecosystem stability with disturbance. Herein is described
      a procedure (soil Nitrolog) for evaluating fungal functional diversity on a suite
      of 95 different N substrates. The soil Nitrolog procedure was evaluated by
      testing fungal functional diversity at two sites in Big Bend National Park
      (Chihuahuan Desert), differing in elevation and plant community composition. The
      soil Nitrolog procedure distinguished between the two sites based on overall use
      of the 95 N substrates. In addition the procedure detected differences in
      individual substrate use based on site specific plant compounds in response to
      changes in the amount of N entering these ecosystems from anthropogenic inputs.

PMID- 16894982
TI  - Ultraviolet and chlorine disinfection of mycobacterium in wastewater: effect of
      aggregation.
AB  - Mycobacteria naturally aggregate in water, a characteristic that may serve to
      protect them against disinfection in wastewater. Secondary effluent was spiked
      with Mycobacterium terrae (M. terrae), sequentially filtered through 100-, 41-,
      and 20-microm nylon filters to partition aggregate sizes, confirmed using
      particle-size analysis and microscopy. Each sample was exposed to doses of UV
      light (10 to 60 mJ/cm2 at 254 nm) and free chlorine (27 to 150 mg-min/L at 4
      degrees C). Inactivation of M. terrae in wastewater was initially rapid, with 2.5
      log reduction at 14 mJ/cm2 and 56 mg-min/L for UV and free chlorine,
      respectively. However, in effluent and 100-microm filtered wastewater, spiked M.
      terrae was present to the highest doses evaluated. Interestingly, M. terrae
      passed through 41- and 20-microm filters were inactivated rapidly, with no
      survivors after moderate disinfection doses. Inactivation of Mycobacteria in
      wastewater may be compromised by aggregates larger than 41 microns.

PMID- 16894981
TI  - Use of hydrophilic and hydrophobic microfiltration membranes to remove
      microorganisms and organic pollutants from primary effluents.
AB  - Primary-effluent wastewater from the Allegheny County Sanitary Authority
      (Pennsylvania) was used as a surrogate for combined-sewer-overflow waters
      contained in the sewershed. Pathogens contained in combined-primary-effluent
      wastewaters or combined-sewer overflows (CSOs) may pose a human-health threat to
      those coming in contact with such receiving waters. Polymeric ultra- and nano
      membranes can be used to capture these microorganisms from CSOs. This research
      investigates the ability of polymeric hydrophobic and hydrophilic membranes,
      ranging in pore size from 0.2 to 0.8 microm, to remove pathogen-indicator
      organisms (Escherichia coli, enterococcus, and fecal coliforms). Membranes, with
      pore size 0.45 microm and smaller, were able to reduce the bacteria levels to
      nondetectable levels, with the sole exception of one membrane with pore size 0.3
      microm.

PMID- 16894983
TI  - Advanced oxidation processes in azo dye wastewater treatment.
AB  - The chemical degradation of synthetic azo dyes color index (C.I.) Acid Orange 7,
      C.I. Direct Orange 39, and C.I. Mordant Yellow 10 has been studied by the
      following advanced oxidation processes: Fenton, Fenton-like, ozonation, peroxone
      without or with addition of solid particles, zeolites HY, and NH4ZSM5.
      Spectrophotometric (UV/visible light spectrum) and total organic carbon
      measurements were used for determination of process efficiency and reaction
      kinetics. The degradation rates are evaluated by determining their rate
      constants. The different hydroxyl radical generation processes were comparatively
      studied, and the most efficient experimental conditions for the degradation of
      organic azo dyes solutions were determined.

PMID- 16894984
TI  - Effect of the location of the inlet and outlet structures on short-circuiting:
      experimental investigation.
AB  - The location of the inlet and outlet structures in a treatment plant (e.g., waste
      stabilization pond) may affect its hydraulic efficiency by increasing short
      circuiting. Therefore, in this paper, the effect of the location of inlet and
      outlet structures was investigated in three laboratory channels of different
      lengths. Nine different combinations of inlet and outlet locations were
      considered for each channel under varying rates of flow. Results showed that the
      placement of the inlet and outlet structures close to the surface and the bottom
      of the pond, respectively, gave the minimum value of short-circuiting. This
      location was, therefore, judged to be the optimum among the nine combinations
      considered. The short-circuiting index was found to increase both with the
      dispersion number and the actual flow velocity, giving correlation coefficients
      of 0.3186 to 0.9258 and 0.8057 to 0.9972, respectively. Although minimization of
      short-circuiting will result in higher hydraulic efficiency, it may not
      necessarily result in higher effluent quality unless the temporal and vertical
      fluctuations of the water column are also considered.

PMID- 16894985
TI  - Degradation of 2,4-dichlorophenol by combining photo-assisted Fenton reaction and
      biological treatment.
AB  - The photo-Fenton reaction effect on the biodegradability improvement of 100 mg/L
      solution of 2,4-dichlorophenol (DCP) has been investigated. Biochemical oxygen
      demand (BOD) at 5 and 21 days, BODn/ chemical oxygen demand (COD) and BODn/total
      organic carbon (TOC) ratios, average oxidation state, and inhibition on activated
      sludge were monitored. For 50 mg/L hydrogen peroxide and 10 mg/L iron(II) initial
      concentrations and 40 minutes of reaction time in the photo-Fenton process, the
      biodegradability of the pretreated solution, measured as BOD5/COD ratio, was
      improved from 0 for the original DCP solution up to 0.18 (BOD21/COD = 0.24). At
      that point, all DCP was eliminated from the solution. To study the effect of the
      pretreatment step, the biological oxidation of pretreated solutions was tested in
      two semicontinuous stirred tank reactors, one operated with activated sludge and
      one with biomass acclimated to phenol. Results showed that more than 80% TOC
      removal could be obtained by codigestion of the pretreated solution with
      municipal wastewater. Total organic carbon removals of approximately 60% were
      also obtained when the sole carbon source for the aerobic reactors was the
      pretreated solution. The hydraulic retention times used in the bioreactors were
      of the same order of magnitude as those used at domestic wastewater treatment
      plants (i.e., between 12 and 24 hours). Kinetic studies based on pseudo-first
      order kinetics have also been carried out. Constants were found to be in range
      0.67 to 1.7 L x g total volatiles suspended solids(-1) x h(-1).

PMID- 16894986
TI  - Kinetics of phenol degradation in an anaerobic fixed-biofilm process.
AB  - A mathematical model was developed to describe phenol degradation in an anaerobic
      fixed-biofilm process. The model incorporates the mechanisms of diffusive mass
      transport and Monod kinetics. The model was solved using a combination of the
      orthogonal collocation method and Gear's method. A pilot-scale column reactor was
      used to verify the model. Batch kinetic tests were conducted independently to
      determine the biokinetic parameters used in the model, while shear loss and
      initial thickness of biofilm were assumed so that the model simulated the
      substrate concentration results well. The removal efficiency for phenol was
      approximately 98.5% at a steady-state condition. The model accurately described
      the effluent substrate concentrations and the sequence of biodegradation in the
      reactor. The model simulations are in agreement with the experimental results.
      The approaches presented in this paper could be used to design fullscale
      anaerobic fixed-biofilm reactor systems for the biodegradation of phenolic
      substrates.

PMID- 16894987
TI  - Anaerobic codigestion of municipal, farm, and industrial organic wastes: a survey
      of recent literature.
AB  - Codigestion of organic wastes is a technology that is increasingly being applied
      for simultaneous treatment of several solid and liquid organic wastes. The main
      advantages of this technology are improved methane yield because of the supply of
      additional nutrients from the codigestates and more efficient use of equipment
      and cost-sharing by processing multiple waste streams in a single facility. Many
      municipal wastewater treatment plants (WWTPs) in industrialized countries
      currently process wastewater sludge in large digesters. Codigestion of organic
      wastes with municipal wastewater sludge can increase digester gas production and
      provide savings in the overall energy costs of plant operations. Methane recovery
      also helps to reduce the emission of greenhouse gases to the atmosphere. The goal
      of this literature survey was to summarize the research conducted in the last
      four years on anaerobic codigestion to identify applications of codigestion at
      WWTPs. Because the solids content in municipal wastewater sludge is low, this
      survey only focuses on codigestion processes operated at relative low solids
      content (slurry mode). Semi-solid or solid codigestion processes were not
      included. Municipal wastewater sludge, the organic fraction of municipal solid
      waste, and cattle manure (CAM) are the main wastes most often used in codigestion
      processes. Wastes that are codigested with these main wastes are wood wastes,
      industrial organic wastes, and farm wastes. These are referred to in this survey
      as codigestates. The literature provides many laboratory studies (batch assays
      and bench-scale digesters) that assess the digestibility of codigestates and
      evaluate the performance and monitoring of codigestion, inhibition of digestion
      by codigestates, the design of the process (e.g., single-stage or two-stage
      processes), and the operation temperature (e.g., mesophilic or thermophilic).
      Only a few reports on pilot- and full-scale studies were found. These evaluate
      general process performance and pretreatment of codigestates, energy production,
      and treatment costs.

PMID- 16894988
TI  - Taking advantage of aerated-anoxic operation in a full-scale University of Cape
      Town process.
AB  - To evaluate the potential benefits or limitations of aeratedanoxic operation in
      high-rate biological nutrient removal processes, we conducted a full-scale
      experiment in a University of Cape Town (UCT)-type wastewater treatment plant by
      reducing oxygen supply and increasing flowrates within one treatment train so
      that aerated-anoxic conditions (i.e., zones that receive oxygen but maintain
      dissolved oxygen concentrations below 0.5 mg/L) could be implemented in a section
      of the aerated zone. With this retrofitted configuration, total nitrogen removal
      increased from 54 to 65%, but was limited by the organic carbon available for
      denitrification. Furthermore, the significant reduction in dissolved oxygen
      concentrations in the aerated zone did not negatively affect enhanced biological
      phosphorus removal, demonstrating that the implementation of an aerated-anoxic
      zone within a UCT-type reactor can contribute to a reduction in operational costs
      and a slight improvement in total nitrogen removal, without compromising the
      extent of phosphorus removal.

PMID- 16894989
TI  - Assessment of morphology for anaerobic-granular particles.
AB  - This study shows that a proper assessment of granule morphology is fundamental
      before applying any mathematical derivation or empirical formula based on the
      shape factor of anaerobic-granular particles to determine granular
      characteristics. The granular images and size distribution of samples observed in
      this study revealed two different dimensions along two axes, which characterize
      these particles as ellipsoids. In the literature, theoretical-settling velocities
      and particle-size distribution of anaerobic granules have been calculated by
      assuming granules as spherical-shaped and using the numerical correlation between
      the size and settling velocity. This resulted in large deviations in results
      reported for settling velocities and size distribution calculated by using
      empirical equations when compared with experimentally measured values. It is
      believed that, because of the nonspherical nature of these particles, errors have
      been made in the earlier studies (which considered these particles as spherical),
      while evaluating granular-physical properties.

PMID- 16894990
TI  - Of: A rational procedure for estimation of greenhouse-gas emissions from
      municipal wastewater treatment plants, H. D. Monteith; H. R. Sahely; H. L.
      Maclean; D. M. Bagley, 77, 390 (2005).

PMID- 16894991
TI  - A Bayesian approach for stochastic white matter tractography.
AB  - White matter fiber bundles in the human brain can be located by tracing the local
      water diffusion in diffusion weighted magnetic resonance imaging (MRI) images. In
      this paper, a novel Bayesian modeling approach for white matter tractography is
      presented. The uncertainty associated with estimated white matter fiber paths is
      investigated, and a method for calculating the probability of a connection
      between two areas in the brain is introduced. The main merits of the presented
      methodology are its simple implementation and its ability to handle noise in a
      theoretically justified way. Theory for estimating global connectivity is also
      presented, as well as a theorem that facilitates the estimation of the parameters
      in a constrained tensor model of the local water diffusion profile.

PMID- 16894992
TI  - Three-class ROC analysis--the equal error utility assumption and the optimality
      of three-class ROC surface using the ideal observer.
AB  - Previously, we have developed a decision model for three-class receiver operating
      characteristic (ROC) analysis based on decision theory. The proposed decision
      model maximizes the expected decision utility under the assumption that incorrect
      decisions have equal utilities under the same hypothesis (equal error utility
      assumption). This assumption reduced the dimensionality of the "general" three
      class ROC analysis and provided a practical figure-of-merit to evaluate the three
      class task performance. However, it also limits the generality of the resulting
      model because the equal error utility assumption will not apply for all clinical
      three-class decision tasks. The goal of this study was to investigate the
      optimality of the proposed three-class decision model with respect to several
      other decision criteria. In particular, besides the maximum expected utility
      (MEU) criterion used in the previous study, we investigated the maximum
      correctness (MC) (or minimum-error), maximum likelihood (ML), and Nyman-Pearson
      (N-P) criteria. We found that by making assumptions for both MEU and N-P
      criteria, all decision criteria lead to the previously-proposed three-class
      decision model. As a result, this model maximizes the expected utility under the
      equal error utility assumption, maximizes the probability of making correct
      decisions, satisfies the N-P criterion in the sense that it maximizes the
      sensitivity of one class given the sensitivities of the other two classes, and
      the resulting ROC surface contains the maximum likelihood decision operating
      point. While the proposed three-class ROC analysis model is not optimal in the
      general sense due to the use of the equal error utility assumption, the range of
      criteria for which it is optimal increases its applicability for evaluating and
      comparing a range of diagnostic systems.

PMID- 16894993
TI  - Ultrasound image segmentation: a survey.
AB  - This paper reviews ultrasound segmentation paper methods, in a broad sense,
      focusing on techniques developed for medical B-mode ultrasound images. First, we
      present a review of articles by clinical application to highlight the approaches
      that have been investigated and degree of validation that has been done in
      different clinical domains. Then, we present a classification of methodology in
      terms of use of prior information. We conclude by selecting ten papers which have
      presented original ideas that have demonstrated particular clinical usefulness or
      potential specific to the ultrasound segmentation problem.

PMID- 16894994
TI  - Analysis of visual search patterns with EMD metric in normalized anatomical
      space.
AB  - Eye movements provide important insight into the cognitive processes underlying
      the visual search tasks. For image understanding, although the visual search
      patterns of different observers while studying the same scene bear some common
      characteristics, the idiosyncrasy associated with individual observers provides
      both research opportunities and challenges. The aim of this paper is to study the
      spatial characteristics of visual search, together with the intrinsic visual
      features of the fixation points for comparing different visual search strategies.
      An analysis framework based on earth mover's distance (EMD) in normalized
      anatomical space is proposed, and the results are demonstrated with high
      resolution computed tomography (HRCT) images of the lungs. The study shows that
      through the effective use of both spatial and feature space representation, it is
      possible to untangle what appear to be uncorrelated fixation distribution
      patterns to reveal common visual search behaviors.

PMID- 16894996
TI  - Support vector analysis of color-Doppler images: a new approach for estimating
      indices of left ventricular function.
AB  - Reliable noninvasive estimators of global left ventricular (LV) chamber function
      remain unavailable. We have previously demonstrated a potential relationship
      between color-Doppler M-mode (CDMM) images and two basic indices of LV function:
      peak-systolic elastance (Emax) and the time-constant of LV relaxation (tau).
      Thus, we hypothesized that these two indices could be estimated noninvasively by
      adequate postprocessing of CDMM recordings. A semiparametric regression (SR)
      version of support vector machine (SVM) is here proposed for building a blind
      model, capable of analyzing CDMM images automatically, as well as complementary
      clinical information. Simultaneous invasive and Doppler tracings were obtained in
      nine mini-pigs in a high-fidelity experimental setup. The model was developed
      using a test and validation leave-one-out design. Reasonably acceptable
      prediction accuracy was obtained for both Emax (intraclass correlation
      coefficient Ric, = 0.81) and tau (Ric, = 0.61). For the first time, a
      quantitative, noninvasive estimation of cardiovascular indices is addressed by
      processing Doppler-echocardiography recordings using a learning-from-samples
      method.

PMID- 16894995
TI  - Penalized-likelihood sinogram restoration for computed tomography.
AB  - We formulate computed tomography (CT) sinogram preprocessing as a statistical
      restoration problem in which the goal is to obtain the best estimate of the line
      integrals needed for reconstruction from the set of noisy, degraded measurements.
      CT measurement data are degraded by a number of factors-including beam hardening
      and off-focal radiation-that produce artifacts in reconstructed images unless
      properly corrected. Currently, such effects are addressed by a sequence of
      sinogram-preprocessing steps, including deconvolution corrections for off-focal
      radiation, that have the potential to amplify noise. Noise itself is generally
      mitigated through apodization of the reconstruction kernel, which effectively
      ignores the measurement statistics, although in high-noise situations adaptive
      filtering methods that loosely model data statistics are sometimes applied. As an
      alternative, we present a general imaging model relating the degraded
      measurements to the sinogram of ideal line integrals and propose to estimate
      these line integrals by iteratively optimizing a statistically based objective
      function. We consider three different strategies for estimating the set of ideal
      line integrals, one based on direct estimation of ideal "monochromatic" line
      integrals that have been corrected for single-material beam hardening, one based
      on estimation of ideal "polychromatic" line integrals that can be readily mapped
      to monochromatic line integrals, and one based on estimation of ideal transmitted
      intensities, from which ideal, monochromatic line integrals can be readily
      estimated. The first two approaches involve maximization of a penalized Poisson
      likelihood objective function while the third involves minimization of a
      quadratic penalized weighted least squares (PWLS) objective applied in the
      transmitted intensity domain. We find that at low exposure levels typical of
      those being considered for screening CT, the Poisson-likelihood based approaches
      outperform the PWLS objective as well as a standard approach based on adaptive
      filtering followed by deconvolution. At higher exposure levels, the approaches
      all perform similarly.

PMID- 16894997
TI  - An efficient forward solver in electrical impedance tomography by spectral
      element method.
AB  - In electrical impedance tomography (EIT), a forward solver capable of predicting
      the voltages on electrodes for a given conductivity distribution is essential for
      reconstruction. The EIT forward solver is normally based on the conventional
      finite element method (FEM). One of the major problems of three-dimensional (3-D)
      EIT is its high demand in computing power and memory since high precision is
      required for obtaining a small secondary field which is typical for a small
      anomaly. This accuracy requirement is also set by the level of noise in the real
      data; although currently the noise level is still an issue, future EIT systems
      should significantly reduce the noise level to be capable of detecting very small
      anomalies. To accurately simulate the forward solution with the FEM, a mesh with
      large number of nodes and elements is usually needed. To overcome this problem,
      we proposed the spectral element method (SEM) for EIT forward problem. With the
      introduction of SEM, a smaller number of nodes and hence less computational time
      and memory are needed to achieve the same or better accuracy in the forward
      solution than the FEM. Numerical results demonstrate the efficiency of the SEM in
      3-D EIT simulation.

PMID- 16894998
TI  - Differentiation of sCJD and vCJD forms by automated analysis of basal ganglia
      intensity distribution in multisequence MRI of the brain--definition and
      evaluation of new MRI-based ratios.
AB  - We present a method for the analysis of basal ganglia (including the thalamus)
      for accurate detection of human spongiform encephalopathy in multisequence
      magnetic resonance imaging (MRI) of the brain. One common feature of most forms
      of prion protein diseases is the appearance of hyperintensities in the deep grey
      matter area of the brain in T2-weighted magnetic resonance (MR) images. We employ
      T1, T2, and Flair-T2 MR sequences for the detection of intensity deviations in
      the internal nuclei. First, the MR data are registered to a probabilistic atlas
      and normalized in intensity. Then smoothing is applied with edge enhancement. The
      segmentation of hyperintensities is performed using a model of the human visual
      system. For more accurate results, a priori anatomical data from a segmented
      atlas are employed to refine the registration and remove false positives. The
      results are robust over the patient data and in accordance with the clinical
      ground truth. Our method further allows the quantification of intensity
      distributions in basal ganglia. The caudate nuclei are highlighted as main areas
      of diagnosis of sporadic Creutzfeldt-Jakob Disease (sCJD), in agreement with the
      histological data. The algorithm permitted the classification of the intensities
      of abnormal signals in sCJD patient FLAIR images with a higher hypersignal in
      caudate nuclei (10/10) and putamen (6/10) than in thalami. Defining normalized
      MRI measures of the intensity relations between the internal grey nuclei of
      patients, we robustly differentiate sCJD and variant CJD (vCJD) patients, in an
      attempt to create an automatic classification tool of human spongiform
      encephalopathies.

PMID- 16894999
TI  - Segmentation methodology for automated classification and differentiation of soft
      tissues in multiband images of high-resolution ultrasonic transmission
      tomography.
AB  - This paper presents a novel segmentation methodology for automated classification
      and differentiation of soft tissues using multiband data obtained with the newly
      developed system of high-resolution ultrasonic transmission tomography (HUTT) for
      imaging biological organs. This methodology extends and combines two existing
      approaches: the L-level set active contour (AC) segmentation approach and the
      agglomerative hierarchical kappa-means approach for unsupervised clustering (UC).
      To prevent the trapping of the current iterative minimization AC algorithm in a
      local minimum, we introduce a multiresolution approach that applies the level set
      functions at successively increasing resolutions of the image data. The resulting
      AC clusters are subsequently rearranged by the UC algorithm that seeks the
      optimal set of clusters yielding the minimum within-cluster distances in the
      feature space. The presented results from Monte Carlo simulations and
      experimental animal-tissue data demonstrate that the proposed methodology
      outperforms other existing methods without depending on heuristic parameters and
      provides a reliable means for soft tissue differentiation in HUTT images.

PMID- 16895000
TI  - Anatomy and flow in normal and ischemic microvasculature based on a novel
      temporal fractal dimension analysis algorithm using contrast enhanced ultrasound.
AB  - Strategies for improvement of blood flow by promoting new vessel growth in
      ischemic tissue are being developed. Recently, contrast-enhanced ultrasound (CEU)
      imaging has been used to assess tissue perfusion in models of ischemia-related
      angiogenesis, growth-factor mediated angiogenesis, and tumor angiogenesis. In
      these studies, microvascular flow is measured in order to assess the total impact
      of adaptations at different vascular levels. High-resolution methods for imaging
      larger vessels have been developed in order to derive "angiograms" of arteries,
      veins, and medium to large microvessels. We describe a novel method of vascular
      bed (microvessel and arterial) characterization of vessel anatomy and flow
      simultaneously, using serial measurement of the fractal dimension (FD) of a
      temporal sequence of CEU images. This method is proposed as an experimental
      methodology to distinguish ischemic from nonischemic tissue. Moreover, an
      improved approach for extracting the FD unique to this application is introduced.

PMID- 16895001
TI  - Markov random field modeling for three-dimensional reconstruction of the left
      ventricle in cardiac angiography.
AB  - This paper reports on a method for left ventricle three-dimensional (3-D)
      reconstruction from two orthogonal ventriculograms. The proposed algorithm is
      voxel-based and takes into account the conical projection geometry associated
      with the biplane image acquisition equipment. The reconstruction process starts
      with an initial ellipsoidal approximation derived from the input ventriculograms.
      This model is subsequently deformed in such a way as to match the input
      projections. To this end, the object is modeled as a 3-D Markov-Gibbs random
      field, and an energy function is defined so that it includes one term that models
      the projections compatibility and another one that includes the space-time
      regularity constraints. The performance of this reconstruction method is
      evaluated by considering the reconstruction of mathematically synthesized
      phantoms and two 3-D binary databases from two orthogonal synthesized
      projections. The method is also tested using real biplane ventriculograms. In
      this case, the performance of the reconstruction is expressed in terms of the
      projection error, which attains values between 9.50% and 11.78 % for two biplane
      sequences including a total of 55 images.

PMID- 16895002
TI  - Multifractal analysis of human retinal vessels.
AB  - In this paper, it is shown that vascular structures of the human retina represent
      geometrical multifractals, characterized by a hierarchy of exponents rather then
      a single fractal dimension. A number of retinal images from the STARE database
      are analyzed, corresponding to both normal and pathological states of the retina.
      In all studied cases, a clearly multifractal behavior is observed, where capacity
      dimension is always found to be larger then the information dimension, which is
      in turn always larger then the correlation dimension, all the three being
      significantly lower then the diffusion limited aggregation (DLA) fractal
      dimension. We also observe a tendency of images corresponding to the pathological
      states of the retina to have lower generalized dimensions and a shifted spectrum
      range, in comparison with the normal cases.

PMID- 16895003
TI  - A novel temporal calibration method for 3-D ultrasound.
AB  - This paper examines a novel approach for temporal calibration of a three
      dimensional (3-D) freehand ultrasound system. A localization system fixed on the
      probe gives the position and orientation of the probe. For quantitative use,
      calibration is needed to correctly localize a B-scan in four-dimensional (4-D) (3
      D+t) space. Temporal latency estimation is defined in a general robust
      formulation using no specific probe motion constraints. Experiments were
      performed on synthetic and real data using a 3-D freehand ultrasound system. The
      achieved precision is lower than the image acquisition rate (40 ms). A validation
      study using a calibration phantom has been performed to evaluate the influence of
      incorrect latency estimation on the 3-D reconstruction procedure. We showed that
      for latency estimation errors less than 40 ms, the 3-D reconstruction errors are
      negligible for volume estimation.

PMID- 16895004
TI  - University of Tennessee College of Dentistry update.

PMID- 16895005
TI  - Is the benefit of early orthodontic treatment worth the burden?
AB  - In summary, early interception of Class III malocclusion is definitely warranted
      for many patients. A careful analysis of the patient's problem, and an analysis
      of the patient's airway is essential if one is to make the correct decision as to
      the amenability of early treatment of the patient's Class III malocclusion. The
      Class I patient, in most instances, especially if the crowding is severe, can be
      favorably impacted with guidance of occlusion. This procedure shortens treatment
      time and lessens the burden for both the patient and the family. Space
      preservation is also a viable procedure if the Class I patient has minor
      mandibular anterior crowding. Early Class II intervention can be attempted if all
      parties concerned know the literature and expectations. Of the three types of
      malocclusions, the Class II malocclusion presents with the most problems, and
      early Class II treatment must be viewed pessimistically.

PMID- 16895006
TI  - Drug induced osteonecrosis of the jaws.

PMID- 16895007
TI  - Profiling gingival crevicular fluid from smoking and non-smoking chronic
      periodontitis patients.
AB  - BACKGROUND: Smoking is a major risk factor for the development and progression of
      chronic periodontitis (CP). Gingival crevicular fluid (GCF) derived from these
      patients contains many proteins that could serve as important diagnostic
      indicators. A protein chip technology called Surface Enhanced Laser
      Desorption/Ionization-Time of Flight-Mass Spectrometry (SELDI-TOF-MS) has
      recently been developed to facilitate protein profiling of complex biological
      mixtures. The hypothesis to be tested was SELDI-TOF-MS could distinguish between
      GCF of CP patients by smoking status and pocket depth. METHODS: GCF samples
      collected before treatment from sixteen CP patients (eight smokers and eight non
      smokers) at both shallow and deep sites were evaluated by SELDI-TOF-MS. Spectral
      fingerprints were constructed for both cohorts and analyzed by a two-way ANOVA
      according to smoking status and pocket depth. Significance threshold was set at p
      < 0.05. Mean molecular weight (MW) peaks and intensities were also analyzed.
      RESULTS: The spectral fingerprints were significantly different between the two
      cohorts when analyzed by ANOVA according to smoking status (p < 0.0001) but not
      pocket depth (p = 0.9876). Also, the mean intensity of many individual MW peaks
      were determined to be significantly different between the two cohorts. Several
      peaks ranging in MW from 11-14 kDa were only detected in the GCF obtained from
      smokers. CONCLUSIONS: This study has demonstrated that profiling of GCF by SELDI
      TOF-MS can distinguish between CP smokers and non-smokers. Moreover, over
      expressed proteins in GCF from smokers may serve as biomarkers for this high risk
      patient population.

PMID- 16895008
TI  - Separation of an endodontic instrument: clinical significance.

PMID- 16895009
TI  - Creating a path of insertion for implant supported restorations adjacent to
      natural teeth.

PMID- 16895010
TI  - Repair of porcelain crowns due to bruxism: a case report.

PMID- 16895011
TI  - When should children have their first dental visit?
AB  - In summary, the goals of infant oral health care are to: Break the cycle of early
      childhood caries; Disrupt the acquisition of harmful microflora; Manage the
      risk/benefit of habits; Establish a dental home for health or harm; Impart
      optimal fluoride protection; and Use anticipatory guidance to arm parents in the
      therapeutic alliance.

PMID- 16895012
TI  - Esthetic design in removable partial prosthodontics.

PMID- 16895013
TI  - Recent contributions to mycobactrial research and capacity building in Ethiopia.

PMID- 16895017
TI  - T cell mediated immune responses in patients with tuberculous lymphadenitis from
      Butajira, southern Ethiopia.
AB  - The control of tuberculosis (TB) requires improved vaccines in addition to
      chemotherapy. It is essential to understand the immune response in tuberculosis
      to successfully evaluate potential vaccines. Current investigations have focused
      on immune responses in pulmonary forms. We studied the T-cell response of
      peripheral blood mononuclear cells (PBMC) from HIV-infected (n=8) and non
      infected patients (n=19) with lymph node tuberculosis to PPD and short-term
      culture filtrates (ST-CF) of M. tuberculosis. PBMC from HIV-negative TB
      lymphadenitis patients proliferated in response to both antigens (p<0.001) and
      produced variably higher levels of IFN-gamma compared to healthy controls
      (p=0.02) (n=19) from the same area. Such responses were suppressed in HIV co
      infected subjects. The results indicate that circulating PBMC in the apparently
      localized form of tuberculous lymphadenitis react to mycobacterial antigens in a
      similar pattern as those of patients with pulmonary disease.

PMID- 16895018
TI  - Female genital tuberculosis in Ethiopia.
AB  - To study the occurrence of female genital tuberculosis (FGTB) in Ethiopia and to
      compare the different methods available for its diagnosis. METHODS: Biopsy or
      curettage samples from twenty-five clinically suspected cases of FGTB were
      investigated with histopathology, smear microscopy, TB culture and PCR for
      mycobacteria. HIV status was determined by ELISA. CD4:CD8 ratio was evaluated by
      flow cytometry. RESULTS: Among the 25 clinically suspected patients investigated,
      only one was AFB smear positive, three were culture positive, seven were
      histology positive and 12 were positive by PCR (a total of 16 positives). Samples
      taken from the fallopian tube were more frequently positive than those from the
      endometrium. CONCLUSIONS: The results showed that FGTB is a significant clinical
      problem in Ethiopia. A combination of PCR with the other available methods was
      found to be the best alternative to achieve sufficient sensitivity and
      specificity for the diagnosis of FGTB in this setting.

PMID- 16895024
TI  - Antimicrobial susceptibility pattern of Helicobacter pylori strains isolated from
      adult dyspeptic patients in Tikur Anbassa University Hospital, Addis Ababa,
      Ethiopia.
AB  - Presently, there is no published information on the antimicrobial susceptibility
      pattern of H. pylori strains in Ethiopia to guide the choice of drug for therapy.
      Therefore, it is becoming clinically relevant to test the in vitro susceptibility
      of H. pylori clinical isolates prior to treating patients. Susceptibility testing
      was performed on 50 clinical H. pylori isolates obtained from adult dyspeptic
      patients referred to the gastrointestinal (GI) Clinic of Tikur Anbassa University
      Hospital. Five antibiotics were evaluated, by using the Episolmeter test (E
      test). The antibiogram of 50 H. pylori clinical isolates showed that all strains
      were sensitive to clarithromycin, erythromycin and tetracycline, while 38/50
      (76%) and 3/50 (6%) of the strains were resistant to metronidazole and
      amoxicillin, respectively. Infection by metronidazole or amoxicillin resistant H.
      pylori is an important factor leading to treatment failure. Testing of all H.
      pylori clinical isolates to metronidazole and amoxicillin is recommended. If it
      is not possible to perform susceptibility tests on each clinical isolate, a
      program to survey the prevalence of resistance should be implemented in a given
      area or population. When treatment of H. pylori infection is indicated in
      dyspeptic patients, the potential availability, simplicity of use, safety and low
      cost of the antimicrobial agents have to be taken into account.

PMID- 16895025
TI  - Complicated peptic ulcer disease in Tikur Anbessa Hospital, Addis Ababa.
AB  - There are few published surgical reports on peptic ulcer disease (PUD) in
      Ethiopia. Of 405 complicated peptic ulcer patients operated on in Tikur Anbessa
      Hospital, Addis Ababa, from 1997 to 2001, the records of 351 patients were
      retrieved and retrospectively analyzed to assess the pattern of PUD complication
      and the outcome of surgical treatment. During the study period, complicated PUD
      patients comprised 3.8% of the total major surgical procedures. The male to
      female ratio was 5.6: 1.0. The mean age was 36.5 +/- 12.7 years. Of 351 patients,
      337 (96%) had abdominal pain, in most epigastric, and 330 (94%) had vomiting as
      presenting complaints. Dehydration was observed in 44 (12.5%). Gastric outlet
      obstruction (GOO) was the commonest complication followed by perforation that
      necessitated surgical intervention. The commonest operative procedure was truncal
      vagotomy and drainage. Nearly 5.0% died in hospital, most from complicated
      perforated peptic ulcer. Follow-up was possible in 262 patients for a mean of
      16.2 +/- 15.0 months. Dumping and diarrhea were observed in 2.7% and 0.4% of the
      patients, respectively. Bile reflux gastritis was encountered in 1.5%. Truncal
      vagotomy and drainage remained to be easily learnable procedures with acceptable
      morbidity and mortality rates.

PMID- 16895026
TI  - Upper gastrointestinal endoscopy: a review of 10,000 cases.
AB  - A total of 10,000 patients underwent upper gastrointestinal endosopy examination
      between August 1979 and October 1994 at Tikur Anbessa Hospital, Addis Ababa. The
      major indications were dyspepsia (59.4%), upper gastrointestinal bleeding (18%)
      and liver disease (10.8%). The other indications include dysphagia (2.2%),
      gastric outlet obstruction (2.1%), postoperative dyspeptic symptoms (1.9%),
      weight loss and/or anemia (1.4%), epigastric mass (0.6%) and odynophagia 0.2%.
      The mean age of the patients and their sex ratio was 36 years and 2:1,
      respectively. Twenty eight percent of the patients had normal findings. The
      commonest abnormal findings include duodenal ulcer (41%), esophageal varices
      (9%), acute gastritis (6%), duodenitis (3.4%), and reflux esophagitis (2.3%).
      Benign gastric ulcer was rare. The ratio of duodenal ulcer to gastric ulcer was
      19.1%. Duodenal ulcer (45.6%), esophageal varices (15.6) and acute gastritis
      (5.7%) were found to be the commonest causes of upper gastrointestinal bleeding.
      The endoscopy or histology diagnosis of cancer in both the esophagus and stomach
      was 2.8% and 1.3%, respectively. The agreement between endoscopy and histology in
      the diagnosis of esophageal and gastric cancer was 80%. There was no major
      complication related to endoscopy or premeditation. Endoscopy is a fairly
      accurate and safe procedure and therefore should be available and applied widely
      for the diagnosis of upper gastrointestinal diseases in Ethiopia.

PMID- 16895027
TI  - Occurrence of intra-ventricular hemorrhage among preterm infants admitted in
      Tikur Anbessa Hospital.
AB  - All preterm babies admitted to the neonatal unit of Tikur Anbessa Hospital (TAH)
      Addis Ababa from November 2000 to November 2001 were followed until discharge or
      death. There were 298 babies with birth weight of less than 2000 gm and
      Gestational age of less than 36 weeks. 56 babies died (56/298 = 28%) and consent
      was obtained to perform autopsy examination on all of them. The mean Gestational
      age was 31 weeks with the range of 26-35 and the mean birth weight was 1377 grams
      with the range of 780-1900 grams. Intra ventricular Hemorrhage (IVH) was seen in
      18 (18/56 = 32%) preterm infants on autopsy examination. IVH occurred on 36.4% of
      cases in preterm infants with birth weight of <1500 gm and gestational age of <32
      weeks. 16/18 (88.8%) of babies who had IVH were less than 1500 grams. All babies
      with IVH were in respiratory distress and required resuscitation. Recommendations
      are made to improve delivery services and neonatal intensive care unit services
      to reduce incidence of IVH in preterm babies.

PMID- 16895028
TI  - The electrocardiogram in healthy northwest Ethiopians.
AB  - The normal values for ECG have not been fully investigated on Ethiopians. This
      cross sectional study was conducted in 1999/2000 to obtain baseline ECG
      information on normal healthy northwest Ethiopians and to find out whether normal
      ranges of ECG parameters in our population differ from those of Caucasians or
      other black Africans. A standard 12-lead electrocardiogram was done in 690
      selected healthy northwest Ethiopians. They were 392 (56.8%) male and 298 (43.2%)
      female with a median age of 23 years. The systolic and diastolic blood pressures
      were within the normal range in all subjects. The total incidence of deviation
      from the accepted normal ECG was recorded in 393 (57.0%) subjects. This was found
      in 294 (75.0%) male and 99 (33.2%) female subjects. The most common type of
      "abnormalities" were high peaked T wave, 104 (26.5%), elevated S-T segment, 70
      (17.8%), and elevated ST segment with high peaked T wave, 32 (10.9%) in male and
      negative or flat T wave, 35 (11.7%) in female. All types of variations were more
      pronounced in young subjects of both sexes and less common in those aged 40 years
      and above. The normal ECG variants found in Ethiopians were similar to those
      found in other subjects of black African origin. In conclusion, the normal
      variants identified in this study must be taken into consideration in the
      interpretation of ECG from cardiac patients which prevents this useful test from
      being understood wrongly.

PMID- 16895029
TI  - Khat (Catha edulis Forsk) chewing, sociodemographic description and its effect on
      academic performance, Jimma University students 2002.
AB  - Khat (Catha edulis Forsk) chewing habit is being a hot issue of discussion nation
      wide. This habit is spreading at an alarming rate among the young generation,
      especially in high schools and higher institutions, where there are intensive
      academic activities. Students in colleges and universities commonly use khat,
      hoping that it improves their academic performance. The main aim of this study
      was to determine the prevalence and socio-demographic correlates of khat chewing
      and its impact on academic performance. A cross sectional study was conducted, in
      January 2002, on a representative sample of 500 students selected by systematic
      random sampling technique from a total of 2073 students who stayed in the
      university at least two years. Out of these, 76.91% were males, 59.53% were
      Orthodox believers, 70.98% were between 16 and 25 years old, and 49.15% were
      Amhara in their ethnic background. The current prevalence of khat chewing was
      estimated to be 24.79%. In this study, 27% of male students, 46.74% of Muslim
      students and 31.30% of Oromo students were found to be khat chewers. Khat chewing
      has a significant association with high income (p < 0.001), with smoking habit (p
      < 0.05) and with coffee drinking habit (p < 0.001). The presence of khat chewers
      in the family and among friends have also a positive association with khat
      chewing habit. The mean cummulative grade point average (CGPA) of non-chewers was
      found to be significantly higher (p < 0.001) than that of chewers. In conclusion,
      the present study depicts that gender, age, religion, ethnicity and income have a
      positive association with the habit of khat chewing. The t-test value showed a
      significant difference between the mean CGPA of Khat chewers and non chewers in
      favor of the later. This indicates that Khat chewing may not help to improve
      academic performance.

PMID- 16895030
TI  - Comparison of computer assisted scan diagnoses and clinical diagnoses of major
      mental disorders in Butajira, rural Ethiopia.
AB  - One of the major difficulties in mental health research is finding suitable
      research instruments. In the last few decades questionnaires that are supposed to
      work in different languages and cultures have been developed by WHO to solve this
      problem. One of such instruments is SCAN, an instrument which uses computer
      algorithm to make a diagnosis. It is meant to be used for semi-structured
      interview by qualified psychiatrists or clinical psychologists. This and a few
      other research instruments have been translated and used in clinical and
      community settings for psychiatric research in Ethiopia over the last few years.
      In this study computer assisted SCAN Diagnoses and clinical diagnoses made by
      trainee psychiatrists in Butajira, a rural setting in Ethiopia, were compared
      Seven hundred twenty nine persons were diagnosed to have schizophrenia and
      bipolar disorder using both methods. The agreement between the clinical and SCAN
      derived diagnosis was shown to be 100% for schizophrenia (Kappa = 1.0). However,
      the agreement between the two methods of diagnosis was shown to be lower when it
      comes to subtypes of schizophrenia. The agreement for the diagnoses of bipolar
      disorder was 95.3%, kappa = 0.9, P < 0.0001 and for depression it was 93.0%,
      kappa = 0.8, p < 0.0001. Taking into account the limited number of psychiatrists
      and clinical psychologists in the third world countries like Ethiopia we have
      shown that using trainees in psychiatry for SCAN interview is a feasible and
      reliable method to identify major categories of mental disorders in community
      studies.

PMID- 16895031
TI  - Unusual presentation of metastatic involvement of a bone.
AB  - Metastatic involvement of a bone below the knee and elbow is rare. If it occurs
      it usually arises from primary tumours of the bronchus or pelvic organs,
      particularly the colon and the bladder. The case of a 58 years old male patient
      with recurrent transitional cell carcinoma of the bladder who presented with
      metastatic involvement of a metatarsal bone is presented. He presented with pain
      and swelling over the right foot. He was given antibiotic and there was no
      improvement, histopathological examination confirmed metastatic involvement of
      the metatarsal bone. To our knowledge, metastatic involvement of a bone below the
      knee has never been reported in Ethiopia.

PMID- 16895032
TI  - Cases of advanced abdominal pregnancies one of which was with viable fetus.
AB  - Cases of advanced abdominal pregnancies, which were admitted to Gondar College of
      Medical sciences teaching hospital, North-western Ethiopia, in the years 2000 and
      2001, are described, and the challenges in the diagnosis and management discussed
      One of these pregnancies resulted in the delivery of a viable fetus.

PMID- 16895033
TI  - Burden of diseases in Amhara region, Ethiopia.
AB  - This community based cross sectional study was conducted to estimate the Burden
      of Diseases in Amhara region of Ethiopia in 1997 - 1998 A total of 7 urban and 14
      rural kebeles (social administrative units) were included in four administrative
      zones where questionnaire on morbidity, disability and mortality were
      administered. A total of 17780 people were included in the study. The total DALY
      was 51775 per 100000 population. The highest number of DALY lost were obtained
      for acute respiratory tract infections (especially children), malaria, diarrhoea,
      tuberculosis, and maternal and perinatal causes. Communicable and maternal and
      perinatal problems contributed to about 68% of the DALY lost. Whereas the
      contribution of noncommunicable diseases was about 17%. Accidents and injuries
      accounted for 6.4% of the DALY lost. The rest 4.9% and 3.7% were attributed to
      long-term disabilities where the cause could not be determined and undetermined
      causes of death respectively. It appears that while the traditional public health
      problems still persist in high prevalence, the so called "diseases of
      civilization" are also emerging thus further stretching the available resources
      for health. The findings of this study can be used to design appropriate
      strategies and use health resources efficiently.

PMID- 16895034
TI  - Acceptability and utilisation of services for voluntary counselling [corrected]
      and testing and sexually transmitted infections in Kahsey Abera Hospital, Humera,
      Tigray, Ethiopia.
AB  - OBJECTIVES: A study was conducted to assess the acceptability and utilization of
      voluntary counselling and testing (VCT) and sexually transmitted infection (STI)
      services in Kahsey Abera Hospital, Humera. METHODS: Retrospective data was taken
      from hospital consultation logbooks from January 2002 to February 2003, and focus
      group discussions were conducted in March 2003 in the community. RESULTS: While
      the services were known and utilization is increasing, important misconceptions
      about the medical services, disease transmission, and STI treatment persist.
      Although hospital care was generally considered of high quality, persons often go
      to pharmacies to self-treat for STIs due to concerns about confidentiality, and
      the stigma of HIV deters many from wanting to know their serostatus. CONCLUSIONS:
      Additional education is needed on HIV/AIDS, STIs, and the medical services
      provided. Education may make use of community health workers or outreach workers
      in a small group where participants can feel comfortable to ask sensitive
      questions. HIV/AIDS treatment is planned for the near future and may be
      significant in reducing HIV/AIDS stigma.

PMID- 16895035
TI  - The impact of water supply on trachoma prevalence.
AB  - In 1998, a baseline study of the prevalence of trachoma was conducted in Dalocha
      District before pipe water supply was made in 1999. This cross-sectional study to
      determine the prevalence of active trachoma in children aged 1-10 years old was
      conducted in the same area in March-May, 2002 to assess the impact of water
      supply on trachoma prevalence. Cluster sampling method was used to identify the
      villages and households in the previously studied five peasant associations. All
      children 1-10 years of age from the selected households were examined for the
      presence of active trachoma (trachomatous follicles, TF, and trachomatous intense
      inflammation, TI). A total of 644 children, 328 (50.9%) males and 316 (49.1)
      females, from 329 households were examined. Of these, 358 (55.6%) had active
      trachoma with 235 (36.5%) having TF and 123 (19.1%) TI. This figure was
      comparable with the previous report from the same age group and area which was
      51.1%. In conclusion, despite improvement in water supply, the difference in the
      overall prevalence of active trachoma was statistically not significant (p-value
      = 0.074) from the result of the previous study. Thus, unless it is accompanied by
      health education to bring about community's behavioral change regarding the
      importance of personal and environmental hygiene, improvement in water supply
      seems to have no effect on the prevalence of active trachoma.

PMID- 16895036
TI  - Pattern of retinal diseases at a teaching eye department, Addis Ababa, Ethiopia.
AB  - The purpose of this study was to evaluate the pattern of retinal diseases as seen
      at a teaching and tertiary eye care center in Addis Ababa. In a descriptive,
      cross-sectional study, all consecutive patients seen at the retina clinic of
      Menelik II Hospital during a 19 months period (January 2000 to August 2001) were
      included in this series. Pertinent demographic and clinical data were recorded
      for all patients. A total of 1390 new patients with retinal diseases were seen at
      the retina clinic during the study period, accounting for 12.5% of the total
      outpatient population of the eye department. The male to female ratio was 1.8 :
      1. The mean age was 45.2 years +/- 17.3 years (range 2 months to 92 years) and
      median of 44.5 years. Two hundred and twenty-four (16.1%) patients were
      bilaterally blind, 465 (33.5%) patients were unilaterally blind, 280 (20.1%)
      patients had bilateral visual impairment and 195 (14.0%) patients had unilateral
      visual impairment, while 213 (15.3%) patients had normal vision. Retinal
      detachment was the commonest cause of both bilateral (54.9%) and unilateral
      blindness (41.2%), while diabetic retinopathy and myopia were the leading causes
      of bilateral visual impairment accounting for 36.8% and 28.2% respectively.
      Retinal vascular diseases accounted for the largest group of patients (38.1%) of
      which diabetic retinopathy accounted for 75.1%. Retinal detachment was the second
      largest group of diseases, accounting for 24.5% of the total. The proportion of
      patients with age-related macular degeneration was only 2.7%. Most of the
      patients presented with advanced disease, which required vitreo-retinal surgery.
      There is a need to improve on the early diagnosis and early referral of retinal
      diseases at primary and secondary care levels. Selected tertiary care centers
      should develop capacity to provide laser and vitreo-retinal surgery. The
      introduction of posterior vitrectomy in Ethiopia is long overdue.

PMID- 16895037
TI  - Cryptosporidium parvum and other instestinal parasites among diarrhoeal patients
      referred to EHNRI in Ethiopia.
AB  - The occurrence of intestinal parasites in patients referred to the Parasitology
      Laboratory of the Ethiopian Health and Nutrition Research Institute (EHNRI), was
      recorded for four consecutive years, 1998-2001. Based on the stool appearance
      i.e. watery, loose, muciod and bloody, 442 diarrhoeal samples were particularly
      selected to allow diagnosis of intestinal parasites with emphasis on coccidian
      intestinal parasites. Wet saline mounts and formol ether concentration method
      with logul's iodine were performed for the detection of cysts, ova, trophozoites
      and larvae of intestinal parasites. Modified Ziehel Nelseen staining of stool
      smears was used to identify Cryptosporidum parvum and Isospora belli. The overall
      detection rate was 79.4% (351/442). The spectrum of positivity with any protozoa
      was 54.3% (240/442) and helminthes 25.1% (111/442). Cryptosporidium parvum was
      identified in 92/442 (20.8%). Isopora belli was identified among 35/442 (7.9%):
      Entamoeba histolytica/dispar scored second with positivity rate of 17.0% (75/442)
      and Giardia lamblia was found in 38/442 (8.6%) stool samples. As compared to
      protozoan parasites, detection rate with helminthes was very low. Among the
      helminthes. Strongyloides stercoralis was found in 38/442 (8.6%). This
      information strengthens the importance of intestinal protozoan parasites with
      recognition of the opportunistic parasites as major causes of diarrhoea. Their
      role in HIV/AIDS patients cannot be over-emphasized. Further awareness for the
      need of establishing different parasitological techniques at health service
      giving centers would enhance better understanding and management of diarrhoeal
      illness.

PMID- 16895038
TI  - Leiomyoma uteri in Ethiopian women: a clinical study.
AB  - A retrospective review of 588 patients with myoma surgically managed at Tikur
      Anbessa teaching hospital, Addis Ababa, Ethiopia, from February 1992-October 2000
      is presented. The objectives of the study were to describe the sociodemographic
      profile, clinical parameters, indications for operation and outcome of management
      of myoma cases surgically managed at the hospital. Data was collected on
      sociodemographic, obstetric, gynecological and other relevant clinical variables
      from the patient's records. Mean age of patients was 35.8 (SD 7.5) years with a
      median parity of 1. Median uterine size was of 16 weeks pregnant uterus. Number
      of myomas removed at myomectomy ranged from 1-50 (Median 2). 98% of myomas were
      fundal and 2% cervical. 40 (6.8%) of the myomas were "delivered" myomas. The
      median duration of the presenting complaints reported by the patients was 1 year.
      Abnormal bleeding was the major presenting complaint (69.2%). In 101 (17.2%) of
      the patients other pelvic pathologies were identified, the majority being ovarian
      tumours. Three hundred sixteen (53.7%) of the patients had an additional medical
      condition encountered mainly anemia and hypertension. Intraoperative and
      postoperative complications were much higher following hysterectomy than
      myomectomy, but duration of operation, intraoperative blood loss and uterine size
      were not much different in the two operations. Reasons for the delay in
      presentation should be addressed by studies so that interventions leading to
      early presentation of patients can be sought. It is proposed that in all
      situations where it is feasible to do so, myomectomy should be performed in
      preference to hysterectomy irrespective of the need for future fertility.

PMID- 16895039
TI  - Thyroid disease in Tikur Anbessa Hospital: a five-year review.
AB  - Diseases of the thyroid are not uncommon particularly in the highlands of
      Ethiopia. To see the pattern of surgical thyroid disorders, a review of operated
      cases of thyroid diseases in the period 1997-2001 was conducted in Tikur Anbessa
      Hospital, Addis Ababa. During the period, 472 patients underwent surgery for
      goiter. Of these, records of 377 patients could be retrieved and form the basis
      for this analysis. The mean age was 35 (range, 15-73) years. The sex ratio, M : F
      was 1: 3.8. The mean duration of symptoms on admission was 7 years. The most
      frequent presenting feature was goiter. Symptoms of airway obstruction and
      hyperthyroidism were not rare. About 12% of patients were clinically and
      biochemically categorized toxic. Location of goiter was specified in 349 cases.
      Of these, 56.7% had bilateral disease. Nodular colloid goiter was the most common
      pathological type. Neoplasm of the thyroid appeared not to be rare. The mean pre-
      and postoperative hospital stays were 12 and 6 days, respectively. About 66% of
      patients had partial or subtotal thyroidectomy. Significant intraoperative
      hemorrhage requiring blood transfusion occurred in 12 (3%) patients. Some post
      operative complications including pneumonia, wound infection, recurrent nerve or
      parathyroid gland injury, and recurrent goiter or hyperthyroidism were noted. One
      case developed thyroid crisis. Less radical surgical procedures, we believe, are
      adequate for all benign and most malignant goiters in Ethiopia. In areas where
      thyroxin is in short supply and follow-up is erratic total thyroidectomy as is
      recommended else where should be reserved for only few selected cases.

PMID- 16895040
TI  - AMBAR as a public health index for assessment of malnutrition in children.
AB  - This is a prospective case control study conducted in Gondar College of Medical
      Sciences Hospital and Gondar Health Center from March 1998 to March 2000 to
      determine the value of different size "AMBAR" to assess malnutrition in children
      age 12 months - 59 months. A total of 191 cases and 191 controls were enrolled in
      this study. In the process, we have developed a modified form of measuring the
      arm circumference by using a locally made bracellet called "AMBAR" of three
      different sizes. Among the three different size "AMBARs", the one with an
      internal diameter of 4 cm was found to be the most appropriate size to diagnose
      Protein Energy Malnutrition (PEM) as compared to the Harvard standard with a
      positive predictive value of 87.6% and negative predictive value of 95%. However
      "AMBAR" with an internal diameter of 3.5 cm has shown a sensitivity of 29% and
      specificity of 100%. The positive predictive value was 100% and Negative
      predictive value was 58%. Since the sensitivity was very low for this size, we
      felt that, it would not be rational to continue computing for "AMBAR" with an
      internal diameter of 3.0 cm. Finally we have concluded that, assessment of
      malnutrition using "AMBAR" 4 cm is a fairly useful method which can be used by
      mothers/caretakers who do not know how to read and write. It is also technically
      simpler to apply and requires inexpensive and easily available apparatus.

PMID- 16895041
TI  - Pulmonary hamartoma in an Ethiopian adult female: case report.
AB  - A 39 years old Ethiopian women presented to Tikur Anbessa Hospital with cough,
      chest pain, haemaptyis and dyspnea and was admitted with the clinical impression
      of bronchogenic carcinoma. Pneumonectomy was performed and tissue section from
      the specimen was reported as pulmonary hamartoma. A detailed description of the
      clinical findings, laboratory data, chest x-ray and pathologic findings presented
      along with a review of the available literature. This is the first case report of
      an endobronchial hamartoma in an Ethiopian patient.

PMID- 16895042
TI  - True hermaphrodite: very unusual type.
AB  - True hermaphrodite is one of the rare gonadal as well as genital abnormality due
      to a defect in sexual differentiation. Here, we are reporting the most unusual
      type of true hermaphrodite diagnosed at the age of 25 years during operation for
      undescended testis, presenting as a case of infertility and failure to ejaculate
      during sexual intercourse. The patient was found to have grossly as well as
      histologically proven left ovary, left fallopian tube and uterus as well as a
      well descended left testis, with totally absent either right fallopian tube and
      ovary or testis. Thus, this is unusual finding to ratify the occurrence of true
      hermaphrodite in the absence of ambiguous external genitalia.

PMID- 16895043
TI  - Dynamic wait-listed designs for randomized trials: new designs for prevention of
      youth suicide.
AB  - BACKGROUND: The traditional wait-listed design, where half are randomly assigned
      to receive the intervention early and half are randomly assigned to receive it
      later, is often acceptable to communities who would not be comfortable with a no
      treatment group. As such this traditional wait-listed design provides an
      excellent opportunity to evaluate short-term impact of an intervention. We
      introduce a new class of wait-listed designs for conducting randomized
      experiments where all subjects receive the intervention, and the timing of the
      intervention is randomly assigned. We use the term "dynamic wait-listed designs"
      to describe this new class. PURPOSE: This paper examines a new class of
      statistical designs where random assignment to intervention condition occurs at
      multiple times in a trial. As an extension of a traditional wait-listed design,
      this dynamic design allows all subjects to receive the intervention at a random
      time. Motivated by our search for increased statistical power in an ongoing
      school-based trial that is testing a program of gatekeeper training to identify
      suicidal youth and refer them to treatment, this new design class is especially
      useful when the primary outcome is a count or rate of occurrence, such as
      suicidal behavior, whose rate can fluctuate over time due to uncontrolled
      factors. METHODS: Statistical power is computed for various dynamic wait-listed
      designs under conditions where the underlying rate of occurrence is allowed to
      vary nonsystematically. We also present as an example a large ongoing trial to
      evaluate a gatekeeper training suicide prevention program in 32 schools which we
      initially began as a classic randomized wait-listed design. The primary outcome
      of interest in this study is the count of the number of children who are
      identified by the school system as having suicidal thoughts or behaviors who are
      then validated as being suicidal by mental health professionals in the community.
      RESULTS: A general result shows that dynamic wait-listed designs always have
      higher statistical power over a traditional wait-listed design. This power
      increase can be substantial. Efficiency gains of 33% are easy to obtain for
      situations where the intervention has a small effect and the variation in rate
      across time is quite high. When the rate variation for an outcome is very low or
      the intervention effect is large, efficiency gains approach 100%. A small
      increase in the number of times where random assignment occurs from 2 - for the
      standard wait-listed design, to say 4 can provide a large reduction in variance.
      Efficiency gains can also be high when converting standard wait-listed design to
      a dynamic one half-way into the study. LIMITATIONS: As with all wait-listed
      designs, dynamic wait-listed designs can only be used to evaluate short-term
      impact. Since all subjects eventually receive the intervention, no comparison can
      be made after the end of the random assignment period. The statistical power
      benefits are primarily limited to outcomes that can be treated as count or time
      to event data. CONCLUSIONS: A dynamic design randomly assigns units - either
      individuals or groups - to start the intervention at varying times during the
      course of the study. This design is useful in testing interventions that screen
      for new or existing cases, as well as testing the scalability of interventions as
      they are disseminated or expanded system wide. They can improve on the
      traditional wait-listed design both in terms of statistical power and robustness
      in the presence of exogenous factors. This paper demonstrates that such designs
      yield smaller standard errors and can achieve higher statistical power than that
      of a standard wait-listed design. Just as important, dynamic designs can also
      help reduce the logistical challenges of implementing an intervention on a wide
      scale. When the intervention requires that significant training resources be
      allocated throughout the study, the dynamic wait-listed design is likely to
      increase the rate of training and lead to a higher level of program
      implementation.

PMID- 16895044
TI  - Comparing the predictive values of diagnostic tests: sample size and analysis for
      paired study designs.
AB  - BACKGROUND: Although statistical methodology is well developed for comparing
      diagnostic tests in terms of their sensitivities and specificities, comparative
      inference about predictive values is not. PURPOSE: In this paper we consider the
      design and analysis of studies comparing the positive and negative predictive
      values of two diagnostic tests that are measured on all subjects. METHODS: We
      focus on comparing tests using the relative positive and negative predictive
      values. We discuss directly estimating these quantities from the data and derive
      analytic variance expressions. Sample size formulas for study design ensue.
      RESULTS: We analyze data on patients with cystic fibrosis to illustrate the
      methodology. This approach is compared and contrasted with an existing regression
      framework that can also be used for similar analysis purposes and yields similar
      results. CONCLUSIONS: We have developed a new approach for comparing the
      predictive values of two tests that gives rise to sample size formulas for study
      design.

PMID- 16895045
TI  - Evaluating linguistic equivalence of patient-reported outcomes in a cancer
      clinical trial.
AB  - BACKGROUND: In order to make meaningful cross-cultural or cross-linguistic
      comparisons of health-related quality of life (HRQL) or to pool international
      research data, it is essential to create unbiased measures that can detect
      clinically important differences. When HRQL scores differ between
      cultural/linguistic groups, it is important to determine whether this reflects
      real group differences, or is the result of systematic measurement variability.
      PURPOSE: To investigate the linguistic measurement equivalence of a cancer
      specific HRQL questionnaire, and to conduct a sensitivity analysis of treatment
      differences in HRQL in a clinical trial. METHODS: Patients with newly diagnosed
      chronic myelogenous leukemia (n = 1049) completed serial HRQL assessments in an
      international Phase III trial. Two types of differential item functioning
      (uniform and non-uniform) were evaluated using item response theory and classical
      test theory approaches. A sensitivity analysis was conducted to compare HRQL
      between treatment arms using items without evidence of differential functioning.
      RESULTS: Among 27 items, nine (33%) did not exhibit any evidence of differential
      functioning in both linguistic comparisons (English versus French, English versus
      German). Although 18 items functioned differently, there was no evidence of
      systematic bias. In a sensitivity analysis, adjustment for differential
      functioning affected the magnitude, but not the direction or interpretation of
      clinical trial treatment arm differences. LIMITATIONS: Sufficient sample sizes
      were available for only three of the eight language groups. Identification of
      differential functioning in two-thirds of the items suggests that current
      psychometric methods may be too sensitive. CONCLUSIONS: Enhanced methodologies
      are needed to differentiate trivial from substantive differential item
      functioning. Systematic variability in HRQL across different groups can be
      evaluated for its effect upon clinical trial results; a practice recommended when
      data are pooled across cultural or linguistic groups to make conclusions about
      treatment effects.

PMID- 16895047
TI  - Problems in comprehension of informed consent in rural and peri-urban Mali, West
      Africa.
AB  - BACKGROUND: Clinical trials undertaken by industrialized nations in undeveloped
      nations pose several critical ethical dilemmas. One key potential problem
      concerns misunderstandings of the consent process by participants. Though other
      reports have begun to explore this area, needs remain to identify specific areas
      of misunderstanding. PURPOSE: To identify deficits in comprehension during
      consent processes in Mali, West Africa. METHODS: After obtaining informed consent
      for participation for a malaria vaccine trial being conducted in two West African
      villages, we administered to participants a nine-item questionnaire testing their
      understanding of information relevant for their consent. After testing their
      ability to understand a multiple choice format, 78 of 100 subjects were
      administered the questionnaire in one village and 85 of 100 in the other.
      RESULTS: Participants had difficulty comprehending several concepts relevant to
      informed consent: 90% of respondents did not understand withdrawal criterion, 93%
      did not understand the existence of study side effects, and 74% did not
      understand that they were enrolled in an investigation as opposed to receiving
      therapy. The response rate and percentage of correct answers was generally much
      higher in the village nearer an urban center than the more rural village. The
      percent of correct answers exceeded 50% for five questions in the urban village
      and for only two question in the more rural setting. LIMITATIONS: Potential
      limitations of this study are relating to translation, cultural differences in
      the notion of informed consent, staff differences between each village, the
      proportion who could not understand the survey instrument and the fact that the
      study explored participants' understanding of the consent process but did not
      observe the process itself. CONCLUSIONS: This study illustrates potential areas
      of miscomprehension in the consent process in a developing country. The degree of
      miscomprehension found in this study appeared to be more than that found in
      similar studies conducted in industrialized nations. Despite efforts to obtain
      truly informed consent, several factors make it more challenging in the
      developing world. This research highlights the need for more comprehensive
      studies of consent in developing countries. Such studies may eventually aid
      investigators in identifying, targeting and addressing specific areas of
      miscomprehension and thereby improve the informed consent process in the
      developing world.

PMID- 16895046
TI  - TREAD: TReatment with Exercise Augmentation for Depression: study rationale and
      design.
AB  - BACKGROUND: Despite recent advancements in the pharmacological treatment of major
      depressive disorder (MDD), over half of patients who receive treatment with
      antidepressant medication do not achieve full remission of symptoms. There is
      evidence that exercise can reduce depressive symptomatology when used as a
      treatment for MDD. However, no randomized controlled trials have evaluated
      exercise as an augmentation strategy for patients with carefully diagnosed MDD
      who remain symptomatic following an adequate acute phase trial of antidepressant
      therapy. PURPOSE: TReatment with Exercise Augmentation for Depression (TREAD) is
      an NIMH-funded, randomized, controlled trial designed to assess the relative
      efficacy of two doses of aerobic exercise to augment selective serotonin reuptake
      inhibitor (SSRI) treatment of MDD. METHODS: The TREAD study includes 12 weeks of
      acute phase treatment with a 12-week post-treatment follow-up. In addition to
      looking at change in depressive symptoms as a primary outcome, it also includes
      comprehensive assessment of psychosocial function and treatment adherence.
      RESULTS: This paper reviews the rationale and design of TREAD and illustrates how
      we address several key issues in contemporary patient-oriented research on MDD:
      1) the use of augmentation strategies in the treatment of depressive disorders in
      general, 2) the use of non-pharmacological strategies in the treatment of
      depressive disorders, 3) the considerations of designing a well-controlled trial
      using two active treatment groups, and 4) the implementation of an adherence
      program for the use of exercise as a treatment strategy. CONCLUSIONS: The TREAD
      study is uniquely designed to overcome sources of potential bias and threats to
      internal and external validity that have limited prior research on the mental
      health effects of exercise. The study is facilitated by the development of a
      multidisciplinary research team that includes experts in both depression
      treatment and exercise physiology, as well as other related fields.

PMID- 16895048
TI  - Guidelines for data and safety monitoring for clinical trials not requiring
      traditional data monitoring committees.
AB  - This is a commissioned report by a writing committee formed by the Society for
      Clinical Trials. The committee was formed with the objectives of 1) reviewing
      data monitoring guidelines for confirmatory (phase III) trials published by the
      National Institutes of Health, US Food and Drug Administration, Veterans
      Administration, and the International Conference on Harmonisation and 2)
      proposing corresponding guidelines for exploratory clinical trials (ie, most
      phase I and phase II trials and others not requiring a fully independent data
      monitoring committee). These trials typically involve fewer subjects and are of
      shorter duration than phase III trials. Nevertheless there are safety concerns,
      especially because these are often the first human trials for a new intervention.
      Recommendations are given for appropriate elements of a data monitoring plan,
      decision criteria for institution of a data monitoring committee (DMC), and
      critical elements for a DMC to consider in exploratory trials. Review and
      approval of data monitoring plans are suggested to fall under Institutional
      Review Board purview. Forming a committee with all the characteristics of a
      traditional phase III trial monitoring committee may be warranted for a small
      fraction of exploratory trials. Such a panel could consist of both trial
      investigators and outside members. The paper concludes with examples of data and
      safety monitoring practice from the University of Wisconsin Comprehensive Cancer
      Center and the AIDS Clinical Trials Groups.

PMID- 16895049
TI  - A tale of three species--rabbits, chickens and humans: an interview with clinical
      trials pioneer Jeremiah Stamler. Interview by Janet Wittes.

PMID- 16895050
TI  - South Dakota and abortion.

PMID- 16895051
TI  - Assisted reproductive technologies in South Dakota: the first ten years.
AB  - One in six couples experience infertility. New assisted reproductive technologies
      such as in vitro fertilization (IVF) have helped thousands of couples worldwide
      to have a family. IVF has been available in South Dakota for the past ten years.
      Improvements in the clinic and laboratory have led to better live birth rates and
      lower incidences of multiple pregnancies. Advances in technology will help even
      more people overcome fertility problems in the near future.

PMID- 16895052
TI  - Spontaneous retropharyngeal hemorrhage causing airway obstruction: a case report
      with a review of the literature.
AB  - Spontaneous retropharyngeal hemorrhage, although uncommon, can be rapidly
      progressive and potentially life-threatening. Timely recognition and appropriate
      treatment are essential for a successful outcome. We report a case of
      retropharyngeal hemorrhage in an 81-year-old male with a history of
      arteriosclerotic disease who presented with cough, dysphagia, dyspnea, and
      cervical ecchymosis. Lateral plain films and computerized tomography (CT)
      revealed a diffuse soft tissue density distending the retropharyngeal space and
      adjacent fascial compartments but sparing the glottic and subglottic airway.
      Emergency tracheostomy was required to relieve progressive upper airway
      obstruction. The literature on spontaneous retropharyngeal hematoma is reviewed
      including clinical presentation, causative factors, and recommended treatment.

PMID- 16895053
TI  - Years in the making: inhaled insulin has finally arrived.

PMID- 16895054
TI  - HB 1215 prosecution risk theoretical, but potentially real.

PMID- 16895055
TI  - Quality focus: South Dakota hospitals commit to transformational quality
      improvement.

PMID- 16895056
TI  - My view.

PMID- 16895057
TI  - [The effect of glycine with timoptol on the rabbit IOP physiological values].
AB  - PURPOSE: the mixture of 10% L-glycine.HCl in 0.5% Timoptol, intensity and
      duration of effect on the physiological IOP is evaluated in this work. METHODS:
      Experiments were performed on 5 rabbits of the New Zealand White species. The
      mixture and its components were individually instilled into the left conjunctival
      sac. The right eye was used as control. RESULTS: after instillation of the 10% L
      glycine.HCl and 0.5% Timoptol mixture the IOP showed significant decrease
      compared with the control eye during 24 hour evaluation. Maximal decrease for 33%
      (8.5 torr) was measured in 60th min., compared with the decrease for 30.5% (7.6
      torr) in 120th and for 28% in 30th min. On the contrary, both substances alone-
      the 10% L-glycine.HC1 and 0.5% Timoptol decrease the physiological IOP values
      only no significantly compared with their mixture and the control eyes. The mean
      value of the pupilar diameter was 7.8 mm on both eyes. CONCLUSIONS: We assume
      that the decrease of the physiological IOP value is caused by a new metabolite-
      the "bioantiglaucomatic" created by interaction of glycine and Timoptol in vitro.
      The effect of this mixture on the decrease of the physiological IOP values is 8
      times stronger compared with Timoptol and 4.3-times stronger compared with
      glycine. Application of such already prepared bioantiglaucomatic in the clinical
      practice can contribute to the more effective, safe and reliable therapeutic
      effect on the IOP in glaucomatic disease.

PMID- 16895058
TI  - [TINU syndrome].
AB  - PURPOSE: To evaluate our experience with the diagnosis and the treatment of the
      TINU syndrome. The term TINU syndrome means the intraocular inflammation
      occurring in association with tubulointerstitial nephritis. The predominance of
      younger females was established. The uveitis is frequently chronic, moderate, and
      bilateral. The treatment with immunosuppressive drugs often has positive clinical
      response. METHODS: A retrospective study. RESULTS: Five patients, 4 women and 1
      man, have been examined and treated for the TINU syndrome in our Department for
      Diagnosis and Treatment of Uveitis. The age ranged from 8 to 62 years. The
      treatment with immunosuppressive drugs caused reduction of the inflammatory
      reaction and visual acuity improvement. CONCLUSION: Immunosuppressive drugs were
      effective in all of our patients suffering from the TINU syndrome. The
      cooperation between ophthalmologist and nephrologist is crucial for the effective
      control of the disease activity and for drug regimen optimization.

PMID- 16895060
TI  - [Antiglaucoma drugs--content of preservatives and the patient's compliance].
AB  - The presence of preservatives in eye drops, may have, depending on the
      concentration, cytotoxic influence on the corneal and conjunctival cells, and may
      cause the patients' subjective inconveniences. The authors compare the
      benzalconium chloride (BAC) concentrations in individual drug used for glaucoma
      treating. The daily dose of BAC was calculated according to the drop's size and
      BAC concentration. The daily dose of BAC differs depending on the selected
      therapy markedly--doses in the range from 0 to 10 micrograms were found. The BAC
      concentration is one of important factors affecting the patient's compliance in
      the treatment of the primary open angle glaucoma.

PMID- 16895059
TI  - [The Slovak study of the travoprost treatment efficacy].
AB  - PURPOSE: To confirm the efficacy of the travoprost treatment during twelve months
      follow-up in groups of patients: without previous treatment, with different
      previous anti-glaucomatous treatment, and with different stage of compensation.
      PATIENTS AND METHODS: The study evaluates the lowering of the intraocular
      pressure (IOP) in 143 patients (286 eyes). The intraocular pressure was measured
      by means of aplanation tonometry, before the treatment started, and after 1, 3,
      9, and 12 months at 8-9 o'clock a.m. Patients were divided into eight groups
      according to the previous mono therapy or combined therapy substituted by
      travoprost mono therapy or its combination. A special group constituted patients
      with travoprost as a primary treatment. RESULTS: In the first group, with
      latanoprost substituted by travoprost, the intraocular pressure decreased by 7%
      (p < or = 0.0001). In the second group of patients, with travoprost as the
      primary glaucoma treatment, the intraocular pressure decreased by 22% (p < or =
      0.0001). In the third group, the beta-blocker was substituted by travoprost, with
      22 % (p < or = 0.0001) decrease of the IOP. In the fourth group, the combined
      therapy of beta-blocker with latanoprost was substituted by combination of beta
      blocker and travoprost and the decrease by 8% (p < or = 0.0001) was significant
      during the first nine months of the follow-up period, later on, the decrease was
      not significant. The substitution of the combination of beta-blocker and
      latanoprost by travoprost mono therapy in the fifth group created only no
      significant lowering of the IOP during the whole follow-up period. If the
      travoprost mono therapy substituted the combination of beta-blocker with local
      carboanhydrase inhibitor in the sixth group, the IOP decreased by 20% (p < or =
      0.001). In the seventh group, the combination of the local carboanhydrase
      inhibitor and latanoprost was substituted by combination of the local
      carboanhydrase inhibitor with travoprost, the IOP lowering was not significant.
      On the other hand, in the eighth group, different combinations of
      antiglaucomatics were substituted by travoprost, and this caused significant
      lowering of IOP by 20% (p < or = 0.0001). In all cases, the lowest decrease of
      IOP during the whole follow-up period in the eye with worse compensation is
      given. CONCLUSION: Travoprost lowered effectively the intraocular pressure in 6
      out of 8 groups of patients, e.g. in 129 patients (out of 143 patients), the
      range of lowering was 7-28% bellow the initial level, the follow up period was 12
      months. The decrease of the IOP was stable. The drug was well tolerated.

PMID- 16895061
TI  - [Surgical treatment of submacular hemorrhage combined with tissue plasminogen
      activator (a case report)].
AB  - Authors present the possibilities of extensive submacular hemorrhage surgery in a
      patient after serious eye injury with bleeding into the vitreous and underneath
      the retina. The combination of vitrectomy with tissue plasminogen activator
      application into the subretinal space allows better to dissolve the coagulated
      blood and facilitates its removal. This procedure with correct operation
      technique decreases the damage of the retinal tissue and consequently preserves
      the photoreceptors' function. In this report, a result of surgical treatment in a
      22-year-old man is presented. In the presence of intravitreal bleeding and
      submacular hemorrhage, during the vitrectomy the tissue plasminogen activator was
      used, which during few minutes dissolved the already coagulated hemorrhage and
      facilitated its whole removal from the subretinal space.

PMID- 16895062
TI  - [Infliximab in the treatment of Wegener's granulomatosis: case report].
AB  - PURPOSE: to evaluate the efficacy of monoclonal anti-tumor necrosis factor alpha
      antibody infliximab in treatment of refractory Wegene's granulomatosis. Clinical
      manifestations of Wegener's granulomatosis at the time of infliximab initiation
      were: proptosis of both eyes due to progressive retrobulbar granulomas, visual
      impairment, optic disc edema, progressive diplopia, sinus and renal involvement.
      The disease was refractory to a treatment with various immunosuppressants,
      including intravenous cyclophosphamide or high doses of mycophenolate mofetil in
      combination with corticosteroids. METHODS: Observational case report. RESULTS:
      the patient received six infusions of infliximab (3 mg/kg) in addition to low
      doses of oral cyclophosphamide and corticosteroids. The interval between the
      first two infusions was 1 week. The interval between the second and third
      infusions was 4 weeks, thereafter 8, 12 and 34 weeks. Following the third
      infusion of infliximab the remission of Wegener's granulomatosis was seen. After
      the regression of retrobulbar granulomas visual acuity increased, ocular motility
      improved, diplopia and optic disc edema decreased. Remission has been maintained
      for 17 months. Infliximab was well tolerated during the short-term follow-up.
      CONCLUSION: Infliximab successfully induced remission in case of sight
      threatening Wegener's granulomatosis in our patient. It seems that infliximab
      provides more effective therapeutic option in treatment of Wegener's
      granulomatosis refractory to standard immunosuppression and offers better
      perspectives for patients with previously poor prognosis. Furthermore, it enables
      reducing the exposure to immunosuppressive drugs.

PMID- 16895063
TI  - [Clear lens extraction in correction of refractive errors ].

PMID- 16895064
TI  - [The victor of Trafalgar--the English naval hero, Lord Horatio Nelson and his
      eyes (29 September 1758--21 October 1805)].

PMID- 16895065
TI  - Can social marketing approaches change community attitudes towards leprosy?
AB  - This essay explores how the concept of social marketing can be employed to change
      attitudes towards leprosy. Firstly, the concept of social marketing is discussed,
      then the attitudes that people have about leprosy, the stigma that people with
      leprosy and their families may face, and the detrimental effects that this can
      have on their lives. The effect of knowledge and education on attitudes towards
      leprosy is discussed, as this can be a key component of social marketing
      campaigns. Various methods of social marketing used to change attitudes and
      reduce stigma are examined, such as mass media campaigns, school based education,
      methods which involve community leaders, and the integration and improvement of
      leprosy services. Principles of social marketing which can lead to the success of
      campaigns such as incorporating local beliefs are emphasized. The success of the
      social marketing campaign in Sri Lanka is described, which aimed to remove the
      fear of leprosy, and to encourage patients to seek and comply with treatment.
      Finally, it is argued that social marketing, used correctly, can be highly
      effective at changing community attitudes towards leprosy, reducing stigma and
      improving the lives of patients, who become able to seek treatment sooner as they
      lose their fear of stigmatization.

PMID- 16895066
TI  - From contagious to chronic: a life course experience with leprosy in Taiwanese
      women.
AB  - This study used the narrative analysis method to explore stories told by
      Taiwanese women who had suffered from leprosy. Twenty-one women from a
      leprosarium, a long-term care centre, and the community participated in either
      focus group discussions or individual interviews. The age range for the
      participants was 54-88, with an average of 68 years old. Physical impairments and
      disabilities of the participants included skin scars, claw fingers, drop feet,
      amputated legs, and facial disfigurement. Their stories were analysed in two
      phases: structural and holistic content analyses. Structural analysis identified
      four life stages: before being diagnosed, after being diagnosed, living with
      leprosy, and the future. Holistic content analysis uncovered common themes in
      each life stage. Findings indicated that stigma was experienced throughout the
      life course of these women. At this stage of life, these women were facing not
      only physical impairments and disabilities from the leprosy, but also the usual
      chronic health problems of the elderly. This study suggests that prevention and
      treatment of leprosy-related physical impairments and chronic diseases are
      important.

PMID- 16895067
TI  - Blink reflex, H-reflex and nerve-conduction alterations in leprosy patients.
AB  - Peripheral nerve lesions are the most important cause of disability in leprosy
      patients. Electrophysiological studies are used in the diagnosis and prognosis of
      neuropathy. Nerve conduction is the most frequently used electrophysiological
      test method to detect neuropathy, although it evaluates only a part of the
      peripheral nervous system. Blink reflex and H-reflex are electrophysiological
      tests which evaluate facial and trigeminal nerve function. This study determined
      the frequencies of blink reflex, H-reflex and motor and sensory nerve conduction
      alterations in twenty five heterogeneous, clinic patients with lepromatous
      leprosy and a control group of 20 healthy subjects. Study results showed a
      decrease in motor and sensory nerve conduction in 40% and 30%, respectively. In
      blink reflex (BR), right R1 was altered in latency in 20% of patients, left R1 in
      20%, right ipsilateral R2 in 16%, left ipsilateral R2 in 20%, and right and left
      contralateral R2 were altered in 32% of patients. There was an absence of H
      reflex in 16% (n = 4) and prolonged latency in 4% (n = 1).

PMID- 16895068
TI  - Cyclosporine A treatment of leprosy patients with chronic neuritis is associated
      with pain control and reduction in antibodies against nerve growth factor.
AB  - OBJECTIVES: Chronic neuritis (CN) is still a major problem in leprosy and is
      difficult to manage in patients who do not respond well to prednisone. In this
      study we (i) evaluate the efficacy of cyclosporine A (CyA) in controlling CN
      patients, and (ii) analyse the presence of anti-NGF antibodies in the sera of
      leprosy patients, and their behaviour during CyA treatment. DESIGN: This was an
      open, prospective, non-comparative study. Sixty-seven leprosy patients in three
      different institutions in Para, Brazil were studied from January, 2001 to
      January, 2004. Of these, 47 had no CN and 20 were leprosy patients suffering from
      CN and taking at least 40 mg/day prednisone to control nerve impairment and pain.
      Patients received 12 months reducing course CyA starting at 5 mg/kg per day. The
      outcome measure was sensory impairment, assessed using Semmes-Weinstein
      monofilament examination (SWME), muscular force and spontaneous or palpation
      related pain. RESULTS: Antibodies against NGF were detected in the sera of
      leprosy patients, which may explain the depletion of NGF in leprosy contributing
      to neuritis, inflammation and loss of cutaneous nociception. The levels of these
      antibodies in CN patients were slightly lower than in patients with no CN.
      However, anti-NGF titres in CN patients treated with CyA were lowered to levels
      similar to those in the normal subjects. There was also improvement in sensory
      impairment, muscular force and pain. CONCLUSIONS: These data suggest that anti
      NGF antibodies are present in the sera of leprosy patients and may influence the
      outcome of neuritis, and that CyA might be a useful drug in controlling nerve
      impairment and pain in leprosy patients.

PMID- 16895069
TI  - Patterns of ocular morbidity and blindness in leprosy--a three centre study in
      Eastern India.
AB  - BACKGROUND: Eye disease and visual impairment due to leprosy are not uncommon,
      but their prevalence and the risk factors for such pathology have yet to be fully
      characterized. METHODS: An observational study of leprosy-affected individuals in
      the community, in three districts in Eastern India was performed to determine the
      prevalence of ocular morbidity and blindness. The subjects were chosen by
      stratified random sampling, according to stage of treatment, or stage of post
      treatment surveillance. Each subject underwent ophthalmic examination according
      to a standard pro-forma. RESULTS: Thirty-three out of 1137 (2.9%) subjects were
      blind according to the WHO classification, and 232/1137 (20.7%) had moderate
      visual impairment. The prevalence of blindness and visual impairment was greatest
      in one centre, Jhalda. Multivariate Logistic Regression analysis showed that
      longer duration of disease, more advanced treatment stage and older age were
      independently associated with blindness. One hundred and forty-one cases (28%) in
      Muzaffarpur, 95 cases (63%) in Saldoha and 378 cases (78%) in Jhalda had active
      or treated multibacillary leprosy. DISCUSSION: The prevalence of blindness in
      leprosy varies in different population groups, with differing patterns of leprosy
      related ocular morbidity, blindness and disease type evident even in different
      areas of the same region. Leprosy screening and surveillance programmes should
      include ocular examination as part of routine screening, particularly in
      individuals with a history of multi-bacillary disease. Individuals with known
      sight- threatening pathology should undergo continued active follow up. Local
      epidemiological studies would enable appropriate programme planning and efficient
      allocation of resources.

PMID- 16895070
TI  - Analysis of gene probes and gene amplification techniques for diagnosis and
      monitoring of treatment in childhood leprosy.
AB  - Nucleic acid sequences of Mycobacterium leprae were detected using gene probes
      hybridizing with targeting ribosomal RNA (16S rRNA), ribosomal DNA (16S rDNA) and
      gene amplification techniques (PCR) in skin lesion of paediatric leprosy patients
      and the effect of treatment on the by these methods. Eighty paediatric leprosy
      patients were included in the study. Most cases (79%) were between 9 and 16 years
      of age. Cases were divided into three groups according to treatment status, viz.
      untreated (30), undergoing treatment (30), and at the end of treatment (20).
      Clinical and slit smear examination for acid fast bacilli (AFB) was performed and
      nucleic acids were extracted and fractionated from skin biopsies. M. leprae
      specific 16S rRNA and 16S rDNA was detected by hybridization with gene probes
      whereas the 36 kDa gene sequence was detected by a gene amplification assay
      (PCR). The cases were classified as paucibacillary (PB) and multibacillary (MB)
      by the standard criteria of WHO (1988). Positivity of 16S rRNA in PB cases
      decreased from 60% in untreated to 10.5% after 4-8 months of treatment whereas
      for 16S r DNA, it decreased from 50% to 21%, for PCR from 70% to 36.8% for the
      same specimen, and all became negative at 1 year. Similar trends were seen in MB
      cases where positivity in smear positive untreated cases decreased from 100% to
      56.2% with 16S rRNA and 42.8% with 16S rDNA and PCR, respectively, after 9-12
      months of treatment and all became negative at 2 years, except one case which
      remained positive with PCR. Similar results were observed in smear negative MB
      cases, 100% positivity detected by 16S r RNA and PCR, 75% detected by 16S rDNA
      decreased to zero after 9-12 months of therapy. This study suggests the potential
      usefulness of gene probes targeting 16S rRNA and 16S rDNA and PCR as supportive
      molecular tools for diagnosis of smear negative evolving MB disease and also
      monitoring the response to treatment, these observations however, needs to be
      validated in prospective follow up studies.

PMID- 16895071
TI  - Effects of risedronate on lumbar bone mineral density, bone resorption, and
      incidence of vertebral fracture in elderly male patients with leprosy.
AB  - There is no well-established treatment for osteoporosis in male patients with
      leprosy, because no clinical trials have examined the efficacy of treatment on
      bone mineral density (BMD) or fracture incidence in such patients. The purpose of
      the present study was to evaluate the therapeutic effect on oral administration
      of risedronate in male osteoporotic patients with leprosy. Twenty-three male
      patients with leprosy, 63-87 years of age, were randomly divided into two
      administration groups: R group (risedronate, 2.5 mg/day, daily) and P group
      (placebo, daily). The BMD of the lumbar spine (L2-L4) was measured by dual-energy
      X-ray absorptiometry, and urinary cross linked N-telopeptides of type I collagen
      (NTX) were assessed at baseline, 6 months, and 12 months after treatment. There
      were no significant differences in age, body mass index, BMD, or urinary NTX
      levels at baseline between the two groups. In the present study, oral
      administration of risedronate apparently prevented vertebral fractures by
      increasing lumbar BMD and caused a significant reduction in urinary NTX levels,
      while oral administration of placebo did not increase the lumbar BMD and prevent
      vertebral fractures due to osteoporosis. The above findings suggested that oral
      administration of risedronate contributed to the prevention of vertebral
      fractures by suppressing bone resorption and increasing in lumbar BMD in the
      elderly male patients with leprosy.

PMID- 16895072
TI  - Contribution of mini-LECS to cluster approach case finding in Kaduna State,
      Nigeria.
AB  - Mini-leprosy elimination campaigns (Mini-LECs) were carried out over a period of
      5 years (2000-2004) in Kaduna State, Nigeria. After careful preparation, the
      campaign team visited areas with a high suspicion of hidden cases in 12 selected
      Local Government Areas (LGAs). During the years of the 12 campaigns, 156 new
      cases of leprosy were detected against an expected number of 70 within the same
      LGAs. The results of the mini-LECs were analysed to find out if this cluster
      approach contributed significantly to the overall leprosy case finding and change
      in the proportion of the multi-bacillary (MB) forms of leprosy among new cases in
      the State. The analysis shows that, at LGA level, the number of cases detected
      during the year of mini-LEC is statistically higher then the expected number of
      cases. The MB proportion at LGA level did not change due to the mini-LEC
      exercises. Due to the limited number of exercises, the impact at state level is
      insignificant. However, the experience at LGA level suggests that with an
      increase in number of mini-LEC campaigns per state per annum an impact at the
      state indicators can be expected. In addition the campaigns should be repeated
      for further yield of new leprosy cases.

PMID- 16895073
TI  - A study of leprosy in children, from a tertiary pediatric hospital in India.

PMID- 16895074
TI  - How sweet it isn't.

PMID- 16895075
TI  - Solutions for licensure.

PMID- 16895076
TI  - Milestone reached in genetic compilation.

PMID- 16895077
TI  - Endodontic techniques for scouting the apical thirds of root canals.
AB  - It might be said that there are as many endodontic instrumentation techniques as
      there are operators, although no two clinicians perform the procedure in exactly
      the same manner. Despite differences, there are basic principles (correct
      diagnosis, adequate access, adequate irrigation, removal of the entire pulp,
      instrumentation to the minor constriction of the apical foramen, three
      dimensional obturation, etc.) whose observance are consistent with long-term
      endodontic success. As a subset of these time-honored principles, there are
      guidelines and techniques for apical third "scouting" and instrumentation, which
      can also be considered universal, irrespective of the particular instruments or
      technique used for canal preparation. The purpose of this paper is to describe a
      scouting technique that is designed to optimize the apical part of root canal
      preparation. The author first heard the word "scouting" used in the context
      described by Dr. Clifford J. Ruddle.

PMID- 16895078
TI  - Amalgam: Its history and perils.
AB  - The current amalgam issue is not new. In the 1840s, there was even an "amalgam
      war" between the dentists who advocated the use of gold as a restorative material
      and those who used silver amalgam as a filling material. There were complaints of
      the ill effects of mercury in the amalgam as a health problem. The split on this
      issue threatened to divide dentistry into two camps: those who used amalgam and
      those who condemned it. The first national dental society in the United States,
      the American Society of Dental Surgeons, had to disband because of the
      controversy. There was even a "New Departure" movement in the 1880s to eliminate
      gold as a restorative material in badly broken down teeth, which could be more
      readily salvaged by the use of material that did not require the force of
      condensation needed to pack a gold foil, then considered the ultimate restorative
      material. However, amalgam has proven to be an excellent restorative material
      with few side effects--amalgam saves teeth.

PMID- 16895079
TI  - The effect of xylitol on Streptococcus mutans in children.
AB  - A study was performed on 91 second-grade students from the Los Angeles Unified
      School District to test the effects of xylitol chewing gum on Streptococcus
      mutans in the saliva. Saliva was collected from students and tested for the first
      time using the new University of California, Los Angeles, monoclonal antibody
      testing method. Students found to have moderate or high levels of salivary S.
      mutans were administered four tablets/day of xylitol gum for three weeks. The
      levels of S. mutans in the saliva of children in the high caries index subgroup
      decreased by 61.7 percent. Xylitol can be dispensed in a public school setting by
      school nurses and can be a very safe, efficient and inexpensive preventative
      measure for children at high risk for dental caries.

PMID- 16895080
TI  - California community residential facilities for individuals with intellectual and
      developmental disabilities.
AB  - Evolving residential requirements for individuals with mild and moderate
      intellectual disabilities and related developmental disabilities increasingly
      place these people in community settings. The increasing numbers of these
      individuals are dependent upon local practitioners for needed health services.
      National and California data are reviewed in an effort to provide a general
      awareness of these community living arrangements, which in turn may assist in the
      delivery and the follow-up of oral health services.

PMID- 16895081
TI  - The devil in Dolores' dentition.

PMID- 16895082
TI  - Estimating the infectious disease risks associated with drinking water in the
      United States.

PMID- 16895083
TI  - Assessing waterborne risks: an introduction.
AB  - Information in this paper can help readers evaluate the results of epidemiologic
      studies of waterborne disease risks. It is important that readers understand the
      various epidemiologic study designs, their strengths and limitations, and
      potential biases. Terminology used by epidemiologists to describe disease risks
      can be confusing. Thus, readers should not only evaluate the adequacy of the
      information to estimate waterborne risks but should also understand how the risk
      was estimated. For example, one author's definition of attributable risk may be
      quite different from another author's in terms of the population to which the
      risk may apply and how it should be interpreted.

PMID- 16895084
TI  - Waterborne outbreaks reported in the United States.
AB  - Epidemic waterborne risks are discussed in this paper. Although the true
      incidence of waterborne illness is not reflected in the currently reported
      outbreak statistics, outbreak surveillance has provided information about the
      important waterborne pathogens, relative degrees of risk associated with water
      sources and treatment processes, and adequacy of regulations. Pathogens and water
      system deficiencies that are identified in outbreaks may also be important causes
      of endemic waterborne illness. In recent years, investigators have identified a
      large number of pathogens responsible for outbreaks, and research has focused on
      their sources, resistance to water disinfection, and removal from drinking water.
      Outbreaks in surface water systems have decreased in the recent decade, most
      likely due to recent regulations and improved treatment efficacy. Of increased
      importance, however, are outbreaks caused by the microbial contamination of water
      distribution systems. In order to better estimate waterborne risks in the United
      States, additional information is needed about the contribution of distribution
      system contaminants to endemic waterborne risks and undetected waterborne
      outbreaks, especially those associated with distribution system contaminants.

PMID- 16895085
TI  - The rate of acute gastrointestinal illness in developed countries.
AB  - This paper reviews estimates of the incidence and prevalence of acute
      gastrointestinal illness (AGI) from 33 studies. These studies include prospective
      cohort studies, retrospective cross-sectional population-based surveys, and
      intervention trials from the United States and six other developed countries
      published since 1953. The incidence and prevalence estimates for AGI reported in
      these studies range from 0.1 to 3.5 episodes per person-year. However,
      comparisons of these rates are problematic owing to significant variation in
      study design, sampling methodology, and case definitions and should be made with
      caution. In the United States, the Centers for Disease Control and Prevention's
      (CDC) Foodborne Diseases Active Surveillance Network (FoodNet) estimates a rate
      of 0.65 episodes of AGI per person-year. This estimate includes diarrhea and/or
      vomiting of infectious or non-infectious origin, with a measure of severity
      (impairment of daily activities or diarrhea duration greater than 1 day), and has
      been adjusted for combined respiratory-gastrointestinal illnesses. However, it
      excludes episodes of diarrhea or vomiting due to any long-lasting or chronic
      illness or condition. Limitations in study design result in an unknown degree of
      uncertainty around this point estimate.

PMID- 16895086
TI  - A review of household drinking water intervention trials and an approach to the
      estimation of endemic waterborne gastroenteritis in the United States.
AB  - The incidence of acute gastrointestinal illness (AGI) attributable to public
      drinking water systems in the United States cannot be directly measured but must
      be estimated based on epidemiologic studies and other information. The randomized
      trial is one study design used to evaluate risks attributable to drinking water.
      In this paper, we review all published randomized trials of drinking water
      interventions in industrialized countries conducted among general immunocompetent
      populations. We then present an approach to estimating the incidence (number of
      cases) of AGI attributable annually to drinking water. To develop a national
      estimate, we integrate trial results with the estimated incidence of AGI using
      necessary assumptions about the estimated number of residents consuming different
      sources of drinking water and the relative quality of the water sources under
      different scenarios. Using this approach we estimate there to be 4.26-11.69
      million cases of AGI annually attributable to public drinking water systems in
      the United States. We believe this preliminary estimate should be updated as new
      data become available.

PMID- 16895087
TI  - Estimates of endemic waterborne risks from community-intervention studies.
AB  - The nature and magnitude of endemic waterborne disease are not well characterized
      in the United States. Epidemiologic studies of various designs can provide an
      estimate of the waterborne attributable risk along with other types of
      information. Community drinking water systems frequently improve their operations
      and may change drinking water treatment and their major source of water. In the
      United States, many of these treatment changes are the result of regulations
      promulgated under the Safe Drinking Water Act. A community-intervention study
      design takes advantage of these "natural" experiments to assess changes in health
      risks. In this paper, we review the community-intervention studies that have
      assessed changes in waterborne gastroenteritis risks among immunocompetent
      populations in industrialized countries. Published results are available from two
      studies in Australia, one study in the United Kingdom, and one study in the
      United States. Preliminary results from two other US studies are also available.
      Although the current information is limited, the risks reported in these
      community-intervention studies can help inform the national estimate of endemic
      waterborne gastroenteritis. Information is provided about endemic waterborne
      risks for unfiltered surface water sources and a groundwater under the influence
      of surface water. Community-intervention studies with recommended study
      modifications should be conducted to better estimate the benefits associated with
      improved drinking water treatment.

PMID- 16895088
TI  - Observational epidemiologic studies of endemic waterborne risks: cohort, case
      control, time-series, and ecologic studies.
AB  - Observational studies have assessed endemic waterborne risks in a number of
      countries. Time-series analyses associated increased water turbidity with
      increased gastroenteritis risks in several public water systems. Several cohort
      studies reported an increased risk of gastroenteritis in populations using
      certain public or individual water systems. Although several case-control studies
      found increased waterborne risks, they also found increased risks associated with
      other exposures. An increased risk of campylobacteriosis was associated with
      drinking untreated water from non-urban areas and some tap waters; other
      significant risks included contaminated poultry and foreign travel. Increased
      risks of cryptosporidiosis and giardiasis were associated with drinking water in
      some populations; other risk factors included foreign travel, day care exposures,
      and swimming. These observational studies provide evidence that some populations
      may be at an increased risk of endemic or sporadic illness from waterborne
      exposures, but not all studies found an increased risk. Differences in waterborne
      risks may be due to differences in water quality. System vulnerabilities and
      contamination likely differed in the areas that were studied. The information
      from these studies may help inform estimates of waterborne illness for the US
      population but is inadequate to estimate a population attributable risk.

PMID- 16895089
TI  - Towards a US national estimate of the risk of endemic waterborne disease--sero
      epidemiologic studies.
AB  - Worldwide literature on serological methods and sero-surveys on waterborne
      pathogens has been reviewed. Outbreak investigation and research reports have
      also been examined to aid understanding of the serological response and
      transmission dynamics. The aim was to seek an estimate of seroprevalence and to
      determine if this could inform the US national estimate of risk for endemic
      waterborne infection associated with public water supplies. Antibody responses
      indicate infection, both symptomatic and asymptomatic, so probably give a truer
      indication of prevalence. Outbreak data can probably be regarded as the upper
      bound for seroprevalence estimations. Antibody is not necessarily protective per
      se but is a good indicator for at least partial resistance to symptomatic
      infection; absence of antibody will normally imply susceptibility. Pathogens
      transmitted by water are commonly transmitted by other routes. However, the fact
      that other transmission routes are more common does not detract from the
      potential protective effect of immunity when waterborne transmission occurs. Data
      indicate that seroprevalence varies widely, reflecting geographic, social and
      hygiene factors, but is generally greater where surface water sources are used
      rather than groundwater. Areas of low seroprevalence may expect a high attack
      rate in the event of contamination of their water supply.

PMID- 16895090
TI  - Use of microbial risk assessment to inform the national estimate of acute
      gastrointestinal illness attributable to microbes in drinking water.
AB  - Microbial risk assessment (MRA) evaluates the likelihood of adverse human health
      effects that occur following exposure to pathogenic microorganisms. This paper
      focuses on the potential use of MRA to provide insight to the national estimate
      of acute gastrointestinal illness (AGI) in the United States among persons served
      by public water systems. This article defines MRA, describes how MRA is
      implemented, provides an overview of the field of MRA and discusses how MRA may
      be useful for characterizing the national estimate. Communities served by
      drinking water systems with relatively contaminated source waters, sub-standard
      treatment facilities, and/or contamination problems in their distribution systems
      are subject to higher risks than communities where such issues are less of a
      concern. Further, the risk of illness attributable to pathogens in drinking water
      in each community can be thought of as the sum of the risk from the treated
      drinking water and the risk from the distribution system. Pathogen-specific MRAS
      could be developed to characterize the risk associated with each of these
      components; however, these assessments are likely to under-estimate the total
      risk from all pathogens attributable to drinking water. Potential methods for
      developing such MRAs are discussed along with their associated limitations.

PMID- 16895091
TI  - The role of disease burden measures in future estimates of endemic waterborne
      disease.
AB  - The 1996 Safe Drinking Water Act amendments require the US Environmental
      Protection Agency and the Centers for Disease Control and Prevention to develop a
      national estimate of the occurrence of waterborne infectious disease that is
      attributable to public drinking water systems in the United States. Much of the
      information for developing the national estimate will be derived from
      epidemiologic data, and the primary outcome of this effort will be an estimate of
      the number of cases of gastrointestinal illness. While quantifying the number of
      these cases provides some measure of waterborne disease impact, the usefulness of
      this measure may be limited because the full spectrum of societal impact also
      involves consideration of the additional effects of these diseases such as
      hospitalization costs and lost productivity. If decision-makers wish to compare
      the impact of waterborne infectious diseases to the impact of some other public
      health concern (e.g. to aid in resource allocation decisions), then a comparison
      of case numbers may prove inadequate. Case numbers alone do not provide
      sufficient information about the severity of different illnesses. Society may
      value the avoidance of a few cases of severely debilitating illness more than it
      values the avoidance of many cases of mild illness. In order to compare disparate
      public health concerns, "burden of disease" measures that incorporate indicators
      of disease severity, costs, or societal values may prove essential for some types
      of decisions. We describe epidemiologic measures of severity, quality adjusted
      life years (QALYs), disability adjusted life years (DALYs), willingness-to-pay,
      and cost-of-illness methods commonly used for burden of disease estimates, and
      discuss how some of these summary measures of burden might be used for waterborne
      disease estimates.

PMID- 16895092
TI  - An approach for developing a national estimate of waterborne disease due to
      drinking water and a national estimate model application.
AB  - In this paper, the US Environmental Protection Agency (EPA) presents an approach
      and a national estimate of drinking water related endemic acute gastrointestinal
      illness (AGI) that uses information from epidemiologic studies. There have been a
      limited number of epidemiologic studies that have measured waterborne disease
      occurrence in the United States. For this analysis, we assume that certain
      unknown incidence of AGI in each public drinking water system is due to drinking
      water and that a statistical distribution of the different incidence rates for
      the population served by each system can be estimated to inform a mean national
      estimate of AGI illness due to drinking water. Data from public water systems
      suggest that the incidence rate of AGI due to drinking water may vary by several
      orders of magnitude. In addition, data from epidemiologic studies show AGI
      incidence due to drinking water ranging from essentially none (or less than the
      study detection level) to a rate of 0.26 cases per person-year. Considering these
      two perspectives collectively, and associated uncertainties, EPA has developed an
      analytical approach and model for generating a national estimate of annual AGI
      illness due to drinking water. EPA developed a national estimate of waterborne
      disease to address, in part, the 1996 Safe Drinking Water Act Amendments. The
      national estimate uses best available science, but also recognizes gaps in the
      data to support some of the model assumptions and uncertainties in the estimate.
      Based on the model presented, EPA estimates a mean incidence of AGI attributable
      to drinking water of 0.06 cases per year (with a 95% credible interval of 0.02
      0.12). The mean estimate represents approximately 8.5% of cases of AGI illness
      due to all causes among the population served by community water systems. The
      estimated incidence translates to 16.4 million cases/year among the same
      population. The estimate illustrates the potential usefulness and challenges of
      the approach, and provides a focus for discussions of data needs and future study
      designs. Areas of major uncertainty that currently limit the usefulness of the
      approach are discussed in the context of the estimate analysis.

PMID- 16895093
TI  - Workshop summary: estimating waterborne disease risks in the United States.
AB  - A workshop was held in Atlanta on July 7-8, 2005, to evaluate the epidemiologic
      and other information available for estimating endemic waterborne illness risks
      in the United States. Each paper written for this special issue was discussed and
      fourteen recommendations were made based on the discussion. In addition, seven
      major data gaps were identified as being key to reducing the uncertainty
      associated with a calculation of a national estimate. This summary is provided to
      help regulatory officials, public health professionals, and others better
      understand the health measures being estimated and adequacy of the current risk
      information. The summary also provides a blueprint for researchers interested in
      studying the endemic and epidemic risks of microbes in drinking water.

PMID- 16895094
TI  - [Reperfusion in acute ST-elevation infarction: Fibrinolysis prior to elective PCI
      impairs the result!].

PMID- 16895095
TI  - [Benzodiazepine treatment in criminal medicine: Careful control and strong
      indications are required].

PMID- 16895098
TI  - [Vascular surgery finally a specialty of its own: Structural changes are now to
      be expected for centralization and care efficiency promotion].

PMID- 16895097
TI  - [New routines for samples transport increase patient safety].

PMID- 16895096
TI  - [Dementia diseases--a systematic review. SBU's summary and conclusions].

PMID- 16895099
TI  - [Cerebral angiography necessary for brain death diagnosis in posterior cranial
      fossa processes. Clinical examination only can be misleading for the examiner].

PMID- 16895100
TI  - [The global health initiative: lot of words, little action].

PMID- 16895101
TI  - [Incidence of Chlamydia infection is increasing and current strategy must be
      questioned].

PMID- 16895102
TI  - [We need a better strategy against Chlamydia infections].

PMID- 16895103
TI  - [Gathering round the Chlamydia infection problems: tests and contact tracing
      necessary--changed sexual behavior is also needed!].

PMID- 16895105
TI  - [Equip the police with defibrillators].

PMID- 16895107
TI  - [From the eye to the visual cortex: imaging of the visual pathways].
AB  - This paper aims to give an overview of the various methods used for imaging of
      the visual pathways from the globe to the visual cortex and some examples of the
      most commonly encountered lesions.

PMID- 16895104
TI  - [No increase of ectopic pregnancies among adolescents].

PMID- 16895108
TI  - [CT-angiography of peripheral arterial diseases: principle and current
      indications].
AB  - Recent advances in multi-detector CT technology, improving the spatial resolution
      and the acquisition time, provide basis for CT-angiography of the abdominal aorta
      and peripheral vessels of the lower extremities. The objective of this review is
      to help the clinician to understand principle of CT-angiography of peripheral
      vessels and to provide an overview of the current clinical applications as well
      as the futures directions in diagnosis, treatment planning and post-therapeutic
      surveillance in peripheral vascular diseases.

PMID- 16895109
TI  - [CT-enteroclysis].
AB  - Computed tomography enteroclysis (CTE) has become a well-defined imaging modality
      for the evaluation of various small bowel disorders. The large volume (2 l) of
      enteral contrast agent administrated via a nasojejunal catheter ensures small
      bowel distension. Following helical CT acquisition is completed by multiplanar
      views. CTE is of particular value in intermediate or advanced Crohn's disease. It
      has become the method of choice for small bowel tumours. The cause and degree of
      low-grade small bowel obstruction is more readily analyzed with the technique of
      CTE than conventional CT. CTE should be selectively used to answer specific
      questions of the small bowel. It essentially contributes to the diagnostic
      quality of modern small bowel imaging, and therefore deserves an established,
      well-defined place among the other available techniques.

PMID- 16895110
TI  - [Clinical and radiological aspects of femoro-acetabular impingement].
AB  - Femoro-acetabular impingement is an etiology of early osteoarthritis. It is a
      dynamic theory of development of arthritis due to bony deformations of the
      acetabulum or the proximal femur. The impingement is diagnosed clinically by the
      impingement and apprehension tests. The realisation of reproducible and
      technically irreproachable standard X-Rays is of first importance to detect the
      subtle but present signs of impingement. The MR arthrography is the best exam for
      detection of intra-articular pathologies with radial sequences allowing to
      establish a precise topography of the lesions. The treatment is most of the time
      surgical to avoid progression of cartilage lesions, either by an open surgical
      dislocation or arthroscopically for selected cases.

PMID- 16895111
TI  - [Percutaneous sacroplasty].
AB  - Sacral insufficiency fracture is a debilitating injury for which no active
      treatment is currently available. It frequently causes significant pain and
      limits activities of daily living in patients with osteoporosis. Percutaneous
      vertebroplasty is a common procedure to alleviate the pain associated with
      thoracic and lumbar vertebral compression fractures. The sacral percutaneous
      cimentoplasty procedure (sacroplasty) has recently been introduced as an
      alternative to medical management of osteoporotic sacral insufficiency fractures.
      The purpose of this article is to illustrate the effectiveness and the utility of
      percutaneous sacroplasty in this kind of pathology and to show how this procedure
      can provide symptom relief without having major complications.

PMID- 16895112
TI  - [Patient dose optimization in pediatric computerized tomography].
AB  - The development of CT applications might become a public health problem if no
      effort is made on the justification and the optimisation of the examinations.
      This paper presents some hints to assure that the risk-benefit compromise remains
      in favour of the patient, especially when one deals with the examinations of
      young patients. In this context a particular attention has to be made on the
      justification of the examination. When performing the acquisition one needs to
      optimise the extension of the volume investigated together with the number of
      acquisition sequences used. Finally, the use of automatic exposure systems, now
      available on all the units, and the use of the Diagnostic Reference Levels (DRL)
      should allow help radiologists to control the exposure of their patients.

PMID- 16895113
TI  - [Autoimmune pancreatitis: a new clinical entity].

PMID- 16895114
TI  - [Management of premature infants at 28 weeks gestational age].

PMID- 16895115
TI  - [Homosexuality and blood donation].

PMID- 16895116
TI  - [Blockage of the CB1 cannabinoid receptor for the prevention of liver cirrhosis
      ].

PMID- 16895117
TI  - [The possible usefulness of an illness].

PMID- 16895118
TI  - U.S. Army Medical Command: disasters, pandemics, and surprises.

PMID- 16895119
TI  - The war-related illness and injury study centers: a resource for deployment
      related health concerns.
AB  - Combat veterans often return from deployment having experienced a wide range of
      exposures, symptoms, and medical conditions. The Department of Veterans Affairs
      established war-related illness and injury study centers to serve combat veterans
      with unexplained illnesses. We report the exposures, clinical status, and
      utilization of 53 combat veterans who participated in the National Referral
      Program (NRP) from January 2002 until March 2004. Participants were primarily
      male (81%) and served in the Persian Gulf War (79%). Common diagnoses were
      chronic fatigue syndrome (n = 23, 43%), neurotic depression (n = 21, 40%), and
      post-traumatic stress disorder (n = 20, 38%). Self-reported exposures related to
      weaponry, disease prophylaxis, environmental hazards, stress, and poor hygiene. A
      small increase in mean SF-36V mental component scores (2.8 points, p = 0.009) and
      use of rehabilitation therapies (1.6 additional visits, p = 0.018) followed the
      NRP referral. The small gain in mental function suggests that the NRP may benefit
      combat veterans with long and complex medical histories.

PMID- 16895120
TI  - Considerations in the aeromedical evacuation of a critically ill blast victim:
      lessons learned.
AB  - Rationale for the decision to transport and assessment of available resources are
      integral components of the decision for aeromedical evacuation of critically ill
      patients. We present the case of a 20-year-old man who sustained significant
      trauma after his vehicle struck a land mine. This case reviews and emphasizes the
      factors to consider in arriving at the decision to transport as well as the
      accurate assessment of available equipment and personnel resources.

PMID- 16895121
TI  - Development of a risk-priority score for category A bioterrorism agents as an aid
      for public health policy.
AB  - In developing public health policy and planning for a bioterrorist attack or
      vaccination of military personnel, the most common method for assigning priority
      is using the probability of attack with a particular agent as the single
      criterion. Using this approach, smallpox is often dismissed as an unlikely
      threat. We aimed to develop an evidence-based, systematic, multifactorial method
      for prioritizing the level of risk of each category A bioterrorism agent. Using
      10 criterion, anthrax scored the highest, followed by smallpox. Tularemia was the
      lowest scoring agent. We suggest that such a system would be useful for
      developing public policy, stockpiling of vaccines and therapeutics, vaccination
      of military personnel, and planning for public health responses to a bioterrorist
      attack.

PMID- 16895122
TI  - A review of 41 upper extremity war injuries and the protective gear worn during
      Operation Enduring Freedom and Operation Iraqi Freedom.
AB  - Forty-one patients with upper extremity war injuries sustained during combat
      operations Operation Enduring Freedom and Operation Iraqi Freedom were reviewed
      to report on protective gear availability and usage at the time of injury.
      Participants treated at the Madigan Army Medical Center occupational therapy
      clinic from August 2004 until February 2005 completed a questionnaire regarding
      injuries sustained during deployment. Overall, 6 injuries were to upper extremity
      regions that were covered with issued protective gear; 21 injuries were to areas
      not covered with issued protective gear (i.e., participant was not wearing issued
      gear), and 22 injuries were to regions that were not covered because no
      protective gear was issued for that body area. Although this study is limited,
      future research would provide valuable insights about the efficacy of current
      body armor and the need for additional or modified gear.

PMID- 16895123
TI  - Missed injuries in military patients with major trauma: original study.
AB  - OBJECTIVE: The incidence and subsequent outcomes of missed injuries and the
      primary factors contributing to each missed injury were analyzed. METHODS:
      Records of 709 trauma patients were reviewed between December 2003 and December
      2004. Demographic data were compared and analyzed for two patient groups: those
      with multiple injuries diagnosed in 24 hours and those with multiple injuries
      diagnosed in >24 hours. RESULTS: Fifty-two missed injuries were determined in 34
      (4.8%) patients. There were significant differences between the patients with and
      without delayed diagnoses, including the mean injury severity scores (23 vs.
      16.9), morbidity, and mortality (p < 0.05 for all). Among 69 contributing factors
      identified, 28 (40.6%) were unavoidable and 41 (59.4%) were potentially
      avoidable. CONCLUSIONS: Missed injuries could usually be encountered in the most
      seriously injured patients, particularly in those with altered levels of
      consciousness. Missed injuries were mostly avoidable and most were the result of
      inadequate clinical examination.

PMID- 16895124
TI  - Land mine injuries in the northernmost border of Greece: our experience at the
      University Hospital of Alexandroupolis during 1991-2003.
AB  - We studied the mortality and morbidity caused by land mine injuries in 169 cases
      that presented at the University General Hospital of Thrace, Alexandroupolis,
      Greece, during the period of 1991 to 2003. The data analyzed included the
      emergency room records, the admission records, and the autopsy records from the
      coroner that provided information on cause of death either in the prehospital
      phase, the initial treatment, or during the period following definitive surgical
      repair. Eleven percent of the casualties were lethally injured, the majority of
      whom died before reaching the hospital. Twenty-eight percent suffered severe
      injuries that required hospitalization and surgical management, placing an
      organizational and financial strain upon the hospital's resources, and 40% bore
      light injuries requiring only ambulatory treatment in the emergency room.

PMID- 16895125
TI  - Hemoptysis and breath-holding diving.
AB  - OBJECTIVE: We aim to present one case with hemoptysis. Pulmonary barotrauma of
      descent (lung squeeze) has been described in breath-hold divers when the lung
      volume becomes smaller than the residual volume, with the effect of increased
      ambient pressure. METHODS: We report one case of hemoptysis in a breath-hold
      diver who dove for exercise of military action. RESULTS: The patient's hemoglobin
      and hematocrit levels were 7.3 g/dL and 26%, respectively. The computed
      tomography of thorax obtained 5 hours after the diving event revealed images
      suggestive of hemoptysis. The diagnosis of hemoptysis was made based on the
      diver's history and computed tomography findings. All of the divers performed
      voluntary diaphragmatic contractions at the beginning of their ascent, while
      their mouths and noses were closed. CONCLUSION: We suggest that the negative
      intrathoracic pressure attributable to the forced attempt to breathe along with
      voluntary diaphragmatic contractions contributes to hemoptysis, since it may
      damage the pulmonary capillaries.

PMID- 16895126
TI  - U.S. Navy and Marine Corps conversion rates for tuberculosis skin testing (1999
      2002), with literature review.
AB  - We examined tuberculosis skin conversion rates for U.S. Navy and Marine Corps
      personnel for 1999 to 2002, using information submitted to the Navy Environmental
      Health Center (Portsmouth, Virginia). The screening of 1,190,866 Navy and Marine
      Corps personnel with tuberculosis skin testing found 17,439 (1.46%) new reactors.
      The annual conversion rate increased from 1.35% in 1999 to 1.33% in 2000, 1.54%
      in 2001, and 1.61% in 2003 [chi2 for trend (df = 1) = 102.368; p = 0.000]. The
      overall conversion rate for aircraft carriers was 0.52%, with significantly
      higher rates for amphibious ships (1.76%; relative risk, 3.33; 95% confidence
      interval, 2.98-3.71; p = 0.000) and Marine units (1.13%; relative risk, 2.17; 95%
      confidence interval, 1.98-2.38; p = 0.000). Annual conversion rates increased
      significantly over the period for aircraft carriers [chi2 for trend (df = 1) =
      4.950; p = 0.02608] and decreased significantly for amphibious ships [chi2 for
      trend (df = 1) = 40.197; p = 0.000]. Conversion rates were consistent with the
      recent historical values for the Navy and Marine Corps.

PMID- 16895128
TI  - Serious mental illness, aging, and utilization patterns among veterans.
AB  - As veterans age, chronic physical and psychiatric conditions increasingly
      challenge the Veterans Health Administration. We examine influences of age and
      diagnosis on health care utilization, within the context of the 1995
      deinstitutionalization policy of the Veterans Health Administration. Veterans
      were hospitalized repeatedly over 5 years with diagnoses of schizophrenia,
      bipolar disorder, depression, or alcohol dependence (N = 7,719). Inpatient days
      decreased 14% from baseline while outpatient (OP) visits increased 63%,
      consistent with deinstitutionalization. In adjusted models, OP utilization
      greatly increased with age, but psychiatric visits-notably alcohol treatment-
      dropped sharply. Emergency visits rose after 1997, particularly for ethnic
      minorities. Individuals ages 35-49 and 50-64 years were the greatest consumers of
      OP care; these large, aging cohorts will continue to require additional services,
      taxing a burdened system. Utilization patterns evolve across the life course,
      requiring foresight to address changing demographic demands. Careful attention to
      mental health utilization patterns may help policy makers and providers
      understand psychiatric needs in older patients.

PMID- 16895127
TI  - Spouses of Persian Gulf War I veterans: medical evaluation of a U.S. cohort.
AB  - Ten years after the 1991 Persian Gulf War (GW I), a comprehensive evaluation of a
      national cohort of deployed veterans (DV) demonstrated a higher prevalence of
      several medical conditions, in comparison to a similarly identified cohort of
      nondeployed veterans (NDV). The present study determined the prevalence of
      medical conditions among nonveteran spouses of these GW I DV and NDV. A cohort of
      490 spouses of GW I DV and 537 spouses of GW I NDV underwent comprehensive face
      to-face examinations. No significant differences in health were detected except
      that spouses of DV were less likely to have one or more of a group of six common
      skin conditions. We conclude that, 10 years after GW I, the general physical
      health of spouses of GW I DV is similar to that of spouses of NDV.

PMID- 16895129
TI  - Variables associated with intimate partner violence in a deploying military
      sample.
AB  - Variables associated with intimate partner violence (IPV) were examined within a
      sample of military personnel preparing to deploy. Soldiers with intimate
      relationships processed for mobilization through Fort Bliss, Texas, completed a
      questionnaire that queried demographic information, relationship satisfaction,
      stress, risky alcohol use behaviors, and tactics used during intimate
      relationship conflict. Four hundred forty-nine deploying soldiers (15.8% of 2,841
      with usable data) reported IPV in the past year. Younger age, less education,
      less relationship satisfaction, more stress, and risky alcohol use behaviors were
      significant individual predictors of engaging in IPV. The results of this study
      are discussed in terms of their implications for targeting efforts to reduce IPV
      among military personnel.

PMID- 16895130
TI  - What was different about exposures reported by male Australian Gulf War veterans
      for the 1991 Persian Gulf War, compared with exposures reported for other
      deployments?
AB  - This study identified chemical and environmental exposures specifically
      associated with the 1991 Persian Gulf War. Exposures were self-reported in a
      postal questionnaire, in the period of 2000-2002, by 1,424 Australian male
      Persian Gulf War veterans in relation to their 1991 Persian Gulf War deployment
      and by 625 Persian Gulf War veterans and 514 members of a military comparison
      group in relation to other active deployments. Six of 28 investigated exposures
      were experienced more frequently during the Persian Gulf War than during other
      deployments; these were exposure to smoke (odds ratio [OR], 4.4; 95% confidence
      interval, 3.0-6.6), exposure to dust (OR, 3.7; 95% confidence interval, 2.6-5.3),
      exposure to chemical warfare agents (OR, 3.9; 95% confidence interval, 2.1-7.9),
      use of respiratory protective equipment (OR, 13.6; 95% confidence interval, 7.6
      26.8), use of nuclear, chemical, and biological protective suits (OR, 8.9; 95%
      confidence interval, 5.4-15.4), and entering/inspecting enemy equipment (OR, 3.1;
      95% confidence interval, 2.1-4.8). Other chemical and environmental exposures
      were not specific to the Persian Gulf War deployment but were also reported in
      relation to other deployments. The number of exposures reported was related to
      service type and number of deployments but not to age or rank.

PMID- 16895131
TI  - Noncontact vital sign monitoring system for isolation unit (casualty care
      system).
AB  - For measuring the vital signs of casualties inside an isolation unit, we
      developed a noncontact vital sign monitoring system using a microwave radar. The
      system was tested on eight healthy volunteers ranging in age from 30 to 48 years.
      The heart and respiratory rates derived by the microwave radar correlated with
      the heart and respiratory rates determined by electrocardiogram and respiratory
      sensor (r = 0.98, p < 0.0001 for heart rate; r = 0.84, p < 0.01 for respiratory
      rate). The exhaled CO and CO2, as a measure of trauma injury, were measured using
      an exhaled gas analyzer. The CO and CO2 concentrations were found to average 3.8
      +/- 4.3 ppm and 2.9 +/- 0.4%, respectively. The expired air temperature and body
      temperature, as indicators of hemorrhagic hypothermia, averaged 31.8 +/- 1.7
      degrees C and 36.2 +/- 0.4 degrees C, respectively. The results show that our
      system is promising for future prehospital application in determining casualty
      conditions for fluid infusions by the Casualty Care System intravenous lines.

PMID- 16895132
TI  - Control of traumatic wound bleeding by compression with a compact elastic
      adhesive dressing.
AB  - OBJECTIVE: Compression dressing has been assumed effective, but never formally
      examined in the field. METHODS: A prospective interventional trial examined
      efficacy and feasibility of an elastic adhesive dressing compression device in
      the arena of the traumatic incident. The primary variable examined was the
      bleeding rate from wounds compared before and after dressing. RESULTS: Sixty-two
      consecutive bleeding wounds resulting from penetrating trauma were treated.
      Bleeding intensity was profuse in 58%, moderate 23%, and mild in 19%. Full
      control of bleeding was achieved in 87%, a significantly diminished rate in 11%,
      and, in 1 case, the technique had no influence on the bleeding rate. The Wilcoxon
      test for variables comparing bleeding rates before and after the procedure
      obtained significant difference (Z = -6.9, p < 0.01). No significant
      complications were observed. Caregivers were highly satisfied in 90% of cases.
      CONCLUSION: Elastic adhesive dressing was observed as an effective and reliable
      technique, demonstrating a high rate of success without complications.

PMID- 16895133
TI  - Benign pneumoperitoneum after colonoscopy: a prospective pilot study.
AB  - Benign pneumoperitoneum is asymptomatic free intraabdominal air and is reported
      to occur occasionally with colonoscopy. Management of benign pneumoperitoneum
      after colonoscopy is controversial and may depend on incidence or etiology. No
      previous studies prospectively investigated the incidence or inciting factors of
      benign pneumoperitoneum resulting from colonoscopy. In this study, 100 patients
      underwent colonoscopy and then radiography of the chest and abdomen to detect
      free air. The average age was 58 +/- 6.2 years, and 48 of the colonoscopies were
      therapeutic. No cases of benign pneumoperitoneum were detected, estimating the
      incidence at 0% to 3% for diagnostic and therapeutic colonoscopy. These data
      indicate that benign pneumoperitoneum attributable to colonoscopy is rare and
      possibly nonexistent. Given the paucity of data favoring the occurrence of benign
      pneumoperitoneum after colonoscopy, we advocate treating all cases of free
      intraabdominal air after colonoscopy as perforations.

PMID- 16895134
TI  - Pilonidal sinus in Japan maritime self-defense force at Yokosuka.
AB  - Pilonidal sinus is known to be common among soldiers but not among Asian
      individuals. Few reports have discussed the occurrence of pilonidal sinus in the
      navy. We analyzed the incidence and etiological factors of 12 cases (11 patients,
      with 1 recurrence) of pilonidal sinus diagnosed between 1998 and 2004 in Japan
      Self-Defense Force Hospital Yokosuka. All patients were male, and all lesions
      were in the sacral area. The patients' average age and body mass index were 29.1
      years and 27.4, respectively. The surgical procedures used were primary closures
      (10 cases, 83.3%) and flaps (two cases, 16.7%), and the number of postoperative
      hospital days averaged 11.8. Pilonidal sinus was not found to be significantly
      common among Japan Self-Defense Force personnel in general (7 of 11 patients with
      pilonidal sinus; not significant); however, it was significantly more common
      among the crew members of Japan Self-Defense Force ships (seven of seven
      patients; p < 0.05), which suggests that the on-board lifestyle contributes to
      the occurrence of pilonidal sinus.

PMID- 16895135
TI  - Comparison of the efficacies of botulinum toxin A and Johnstone pressure splints
      against hip adductor spasticity among patients with cerebral palsy: a randomized
      trial.
AB  - OBJECTIVE: The goal was to compare the efficacies of botulinum toxin A (BTX)
      treatment and Johnstone pressure splint (JPS) treatment against hip adductor
      muscle spasticity among children with spastic diplegic cerebral palsy. METHODS:
      For each patient in the BTX group, a total of 300 IU of BTX was injected into
      adductor and medial hamstring muscle groups. In the JPS group, long leg JPS were
      administered for 30 minutes 3 days per week. Bobath neurodevelopmental exercises
      were administered to both groups 3 days per week during the study period. All
      cases were assessed by using gross motor function measurements, passive hip
      abduction goniometric measurements, modified Ashworth Scale scores, and
      measurements of the distance between the knees as indicator variables. RESULTS:
      We found that there was statistically significant improvement in all indicators
      for both groups. BTX treatment was found to be superior to JPS treatment in terms
      of the indicator variables of our study.

PMID- 16895136
TI  - Rhabdomyolysis in the military: recognizing late-onset very long-chain acyl Co-A
      dehydrogenase deficiency.
AB  - Very long-chain acyl Co-A dehydrogenase deficiency, an inborn error of lipid
      metabolism, is commonly thought of as a disease of infancy or early childhood.
      However, several cases of late-onset very long-chain acyl Co-A dehydrogenase have
      been reported. This report of two military men who survived basic training before
      their disease presentation broadens the spectrum of late-onset disease, presents
      two previously unreported mutations, and demonstrates the fine line between
      athletic, active lifestyle and severe disease presentation.

PMID- 16895137
TI  - Endovascular repair of a large post-traumatic calf pseudoaneurysm and
      arteriovenous fistula.
AB  - Endovascular techniques are being increasingly used as the definitive method of
      repair for various traumatic vascular injuries. This case report describes the
      use of transcatheter embolization and direct percutaneous thrombin injection used
      in the definitive treatment of a lower extremity posttraumatic pseudoaneurysm and
      arteriovenous fistula.

PMID- 16895138
TI  - Self-rated health and health care utilization after military deployments.
AB  - Self-rated general health is one element of the standard health assessment
      required of U.S. military service members upon completion of major deployments. A
      cohort study of 22,229 male U.S. Army and Air Force personnel returning from
      Europe or Southwest Asia in 2000 used survival analysis methods and Cox
      proportional hazard models to examine postdeployment self-rated health (SRH)
      status and subsequent hospitalization, separation, and ambulatory care visits.
      Self-rated health was fair/poor for 1.5% and good for 20.4%; 11% documented at
      least one health concern. During 30,433 person-years of follow-up (median, 1.5
      person-years), there were 22.8 hospitalizations per 1,000 person-years and 4.0
      ambulatory care visits per person-years. After adjustment, deployers with
      fair/poor SRH had an increased risk for hospitalization (hazard ratio [HRI, 1.6;
      95% confidence interval [CI], 1.0,2.7); the risk was lower for those with good
      SRH (HR, 1.3; 95% CI,1.1,1.5). Deployers with fair/poor SRH health had an
      increased risk for illness-related ambulatory care visits (HR, 1.8, 95%; CI,
      1.6,2.1) and administrative visits (HR, 1.4; 95% CI, 1.1,1.7), but not injury
      related visits (HR, 1.2; 95% CI, 0.8,1.7). Self-reported low health status and
      other health concerns identify military members with higher levels of health care
      needs following return from major deployments.

PMID- 16895139
TI  - The basis for prescribed ability group run speeds and distances in U.S. Army
      basic combat training.
AB  - During the first few days of Army Basic Combat Training (BCT), recruits take a
      running test and after completing this test they are ranked from fast to slow.
      Four roughly equal-sized "ability groups" are established from these rankings and
      recruits run together in these groups for their physical training during BCT. In
      the past, there has been no formal guidance regarding how fast or how far these
      ability groups should run. To fill this void, this study provides guidance for
      running speeds and distances during BCT. The major considerations included are:
      (1) minimizing injuries, (2) the initial aerobic fitness level of recruits, (3)
      historical improvements in run times during BCT, (4) historical running speeds of
      the slower individuals in each ability group, (5) running speeds that must be
      achieved to "pass" the 2-mile run in BCT, (6) the gender composition of the
      ability groups, and (7) recommendations from the trainers and field testing.
      Three databases were analyzed that contained a total of 16,716 men and 11,600
      women. Four steps were used in the analyses: (1) establishment of run-time cut
      points for representative ability groups, (2) determination of initial (starting)
      run speeds, (3) estimation of changes in run speeds with training, and (4)
      establishment of run speeds and distances for each week of BCT. Efforts were made
      to (1) keep the running speeds between 70% and 83% of the estimated maximal
      oxygen uptake (VO2max) for all ability groups, (2) consider the 2-mile running
      pace of the slower individuals in each ability group, and (3) keep the total
      running distance for the two slower ability groups below a total of 25 miles, the
      apparent threshold for increasing injury incidence. A chart provides speeds and
      distances for each ability group at each week of BCT. Using these recommended
      speeds and distances should allow trainees to improve their aerobic fitness, pass
      the Army Physical Fitness Test, and minimize injuries that result in lost
      training time and, ultimately, lower fitness levels.

PMID- 16895140
TI  - Attitudes toward intentional weight loss and dietary behavior among U.S. Army
      reserve soldiers during annual training.
AB  - OBJECTIVE: The command of a U.S. Army Reserve Combat Support Hospital designed
      this study to evaluate soldiers' behavior related to and attitudes toward
      skipping meals while on annual training (AT). METHODS: The command administered
      an anonymous survey on attitudes about weight loss and weightloss behavior while
      on AT. Of 180 soldiers given the opportunity to respond, 100 responses were
      received (55%). RESULTS: Before AT, 50% of reservists responding thought about
      losing weight while on AT, 62% of soldiers were trying to lose weight while on
      AT, and 25% of soldiers skipped meals. Soldiers who felt that they were
      overweight had a 2.9-fold increased risk for skipping meals, and those who
      thought about losing weight before AT had a 3.0-fold risk. Neither age, gender,
      rank, nor history of previously being on weight control was a predictor of
      skipping meals. CONCLUSION: Most soldiers considered and tried to lose weight
      while at AT, and soldiers who considered themselves overweight or thought about
      losing weight were at increased risk for skipping meals.

PMID- 16895141
TI  - Case management study Walter Reed Army Medical Center. A 37-year-old soldier with
      right flank pain.
AB  - The objective of this study was to discuss the appropriate diagnostic and
      treatment approach to an active duty patient presenting with recurrent kidney
      stones. A 37-year-old active duty infantryman, stationed in Iraq, was evacuated
      by air to Waiter Reed Army Medical Center for workup of recurrent kidney stones
      and hypercalcemia. A diagnosis was made and the definitive treatment was
      performed. During this report, we will illustrate the various aspects of
      diagnosis that are involved with the workup of kidney stones and hypercalcemia as
      well as discuss the available treatment options. Relevant military issues include
      proceeding with the initial management regimen and recognition of appropriate
      reasons for initiation of referral consultation.

PMID- 16895142
TI  - A randomized controlled trial of a leg orthosis versus traditional treatment for
      soldiers with shin splints: a pilot study.

PMID- 16895143
TI  - Military personnel are regularly immunized with Vi polysaccharide typhoid
      vaccines.

PMID- 16895144
TI  - Answer to last month's radiology case and image: Subdural hematoma.

PMID- 16895146
TI  - Adolescent cover art objectionable.

PMID- 16895145
TI  - Improving immunization rates: practical tips.

PMID- 16895147
TI  - A 4-month-old girl with bilious emesis.

PMID- 16895148
TI  - Maximizing office-based immunization.
AB  - Vaccines are a great public health achievement only if we can deliver those
      vaccines to individual patients. It is impressive that gradually increasing
      immunization rates are so consistent in spite of a new birth cohort every year,
      complexity of the schedule, shortages, changes in reimbursement policies, and
      vaccine news stories. Pediatricians have always embraced their public health
      role, especially as immunization providers. By helping practices improve their
      immunization delivery system, rates can be raised throughout a community by first
      maximizing office-based immunization.

PMID- 16895149
TI  - Improving immunization rates in practice settings.
AB  - Many pediatricians do not know the immunization rate of patients in their
      practice. Evidence-based standards of practice have been established, leading to
      improved rates. Quality improvement efforts aimed at immunization are effective
      and may lead to improvement in other preventive health services. By providing
      more vaccines in the medical home, communities can decrease the need for higher
      cost case management and outreach services targeting patients with delayed
      immunizations.

PMID- 16895150
TI  - Using a registry to improve immunization delivery.
AB  - The NJIPSP was successful in encouraging a group of small urban practices to
      adopt the use of immunization registry and to transform immunization delivery
      from a mechanistic well-child service to a visible, monitored process of care.
      The project represents a unique combination of technology, public-private
      collaboration, and well-established quality improvement techniques. The change
      process involved the whole office as a team in adopting new immunization delivery
      roles and services. The greatest barrier to acceptance of the registry was (and
      continues to be) the need for manual data entry as the primary source of data
      collection, rather than electronic data transfer from other systems. The manual
      entry of data was labor intensive for participating practices and affected data
      measurement. Despite this barrier, however, the majority of practices
      substantially improved the quality of their immunization delivery practices in
      multiple areas. The rapid movement of primary care practices toward some form of
      electronic record may reduce this barrier and increase the percentage of
      practices willing to use a community registry. Practices that engaged
      collectively in the change process gained momentum from the group effort. Equally
      important was the public health partnership that helped identify and reduce
      improvement obstacles. Sustainability of practice-based immunization changes will
      rely, in part, on the registry's ease of use and the continued visibility of
      public health at the practice level. Active practice level collaboration by
      public health adds great value to change efforts. We believe that the best
      possible immunization delivery relies on both technology (registries and the EMR)
      and effective office systems. Projects like the NJIPSP are models for systems
      that integrate technology, practice change, and quality improvement, and their
      success has the potential to foster the spread of this approach to other primary
      care practices (especially in New Jersey). The NJIPSP combination of office-based
      change approaches and an active partnership and hands on involvement with public
      health has the potential to support the delivery of consistently excellent
      immunization delivery.

PMID- 16895151
TI  - Coding and payment for immunizations.
AB  - To maximize reimbursement rates for services related to immunization delivery,
      pediatricians must develop a best-practice five step action plan for providing
      immunizations in practice. These include: Implementing optimal coding practices
      for immunization administration and vaccine products; Capturing the work of
      associated evaluation and management services with coding; Supporting CPT coding
      with appropriate ICD-9-CM diagnostic coding links; Incorporating an immunization
      coding menu, including CPT and ICD-9-CM codes discussed in this article, into the
      standard practice encounter form; and Aggressively contracting with payers for
      adequate, flexible payment for immunization services. With knowledge of
      immunization CPT and ICD-9-CM coding, as well as coding for association E/M
      visits, the pediatrican is well prepared to deliver immunizations in the medical
      home.

PMID- 16895152
TI  - Linking practices with community programs to improve immunization rates.
AB  - Pediatricians should be knowledgeable about programs available in their community
      and support efforts to collaborate with other providers, public health
      departments and immunization coalitions in their community. Through immunization
      coalitions and widespread use of an immunization registry, together with
      participating private providers, case management and home visitation programs can
      improve immunization rates among the highest risk children.

PMID- 16895153
TI  - Nursing and other medical staff issues in vaccine administration.

PMID- 16895154
TI  - The effects of varying group size on the reading recovery approach to preventive
      early intervention.

PMID- 16895155
TI  - Letter knowledge, phonological processing, and print knowledge: skill development
      in nonreading preschool children.
AB  - Development of reading skills was examined in 4-year-old children from low-income
      homes attending a prekindergarten program. Fall to spring gains in letter
      identification were examined and compared with skills in phonological processing,
      rhyme detection, and environmental print, and with performance on a screening
      tool (Get Ready to Read). It was anticipated that participants might show slow
      skill development. However, the identification of a large group of children (n =
      30) who made little or no gains in letter identification compared to their
      classmates (n = 27), whose gains averaged 7 letters, was not anticipated. Fall to
      spring gains in letter identification correlated with phonological processing,
      rhyme detection, environmental print, and Get Ready to Read! scores. Age and
      general cognitive skills influenced performance on some tasks. More knowledge of
      the characteristics of children who show the most variations in skill development
      may lead to insights on using classroom curriculum to focus on skill development.

PMID- 16895156
TI  - Enhancing early literacy skills for preschool children: bringing a professional
      development model to scale.
AB  - A quasi-experimental, statewide intervention targeting preschool teachers'
      enhancement of children's language and early literacy was evaluated. Across 2
      years and 20 Head Start sites, 750 teachers participated (500 target, 250
      control), with 370 classrooms randomly selected to conduct pre- and posttest
      assessments (10 randomly selected children per class). The inability to randomize
      children to classrooms was addressed by examining children's performance for
      teachers who were control teachers in Year 1 and target teachers in Year 2. We
      also compared teachers with 2 years of training with teachers with 1 year of
      training and with control teachers. Greater gains were found for children in
      target classrooms than for those in control classrooms for all skills, but
      particularly for language skills, in Year 2, and this varied by program site. The
      presence of a research-based early literacy curriculum, higher levels of teacher
      education, and full-day versus half-day programs were significant moderators of
      intervention effectiveness. The challenges of implementing a statewide initiative
      across programs that varied in their readiness to implement a cognitively rich
      experience for preschool children are discussed.

PMID- 16895157
TI  - Young readers' use of phonological information: phonological awareness, memory,
      and comprehension.
AB  - In this study, we explored the relationship between beginning readers'
      phonological awareness and other aspects of phonological processing, specifically
      as manifested in short-term memory and comprehension tasks. The theoretical
      questions underlying the study were (a) what roles phonological processes play in
      children's beginning reading, from word identification through sentence
      comprehension, and (b) whether those roles are sufficiently related that
      potential difficulties at one level directly affect processing at other levels.
      Phonologically induced effects were observed for word-list memory and for
      sentence judgments for both novice readers (at the end of kindergarten) and
      relatively more experienced readers (end of Grades 1 and 2). For both age groups,
      correlational analyses revealed relationships among phonological awareness,
      phonological processing in list memory, and word reading. However, phonological
      processing in sentence comprehension was not related to other types of
      phonological processing. These results indicate that although phonology plays a
      role during comprehension, phonological processing may not be as limiting a
      factor in comprehension as in word reading.

PMID- 16895158
TI  - Paths to reading comprehension in at-risk second-grade readers.
AB  - Two studies of second graders at risk for reading disability, which were guided
      by levels of language and functional reading system theory, focused on reading
      comprehension in this population. In Study 1 (n = 96), confirmatory factor
      analysis of five comprehension measures loaded on one factor in both fall and
      spring of second grade. Phonological decoding predicted accuracy of real-word
      reading; automatic letter naming predicted rate of real-word reading; accuracy
      and rate of both real-word reading (more so than decoding of pseudowords) and
      text reading predicted reading comprehension; and Verbal IQ also predicted
      reading comprehension. In Study 2 (n = 98), the treatment group (before/after
      school clubs receiving an integrated instructional approach that was
      supplementary to the general reading program) improved significantly more in
      phonological decoding and state standards for reading fluency than the control
      group (general reading program that had some code instruction but emphasized
      comprehension). The rate of phonological decoding explained 60.3% of real-word
      reading. Both treatment and control children improved significantly in reading
      comprehension, but controlling for pretreatment individual differences in oral
      vocabulary or in phonological decoding eliminated this effect. Taken together,
      the results of the two studies support two paths to reading comprehension: one
      from vocabulary and verbal reasoning, and one from written language that has
      multiple links between subskills: (a) alphabetic principle --> phonological
      decoding, (b) automatic phonological decoding --> accurate real-word reading, (c)
      automatic letter coding ---> automatic word reading, and (d) automatic word
      reading --> fluent text reading. Instructional implications of both paths and the
      links within the written language are discussed.

PMID- 16895159
TI  - Below-average, average, and above-average readers engage different and similar
      brain regions while reading.
AB  - Event-related potentials (ERPs) were recorded from 27 children (14 girls, 13
      boys) who varied in their reading skill levels. Both behavior performance
      measures recorded during the ERP word classification task and the ERP responses
      themselves discriminated between children with above-average, average, and below
      average reading skills. ERP amplitudes and peak latencies decreased as reading
      skills increased. Furthermore, hemisphere differences increased with higher
      reading skill levels. Sex differences were also related to ERP amplitude
      variations across the scalp. However, ERPs recorded from boys and girls did not
      differ as a function of differences in the children's reading levels.

PMID- 16895161
TI  - Consultation and management of patients with lipid disorders: importance of life
      style changes and intensive follow-up.
AB  - The purpose was to compare long-term involvement (LTI) vs short-term involvement
      (STI) of patients in a Lipid Education Service (LES) and to assess the effects of
      life-style changes. Patients were referred for LTI and STI by their physicians.
      Three-hundred eighty-one consecutive patients, 287 LTI and 94 STI, were analyzed.
      The lipids in LTI patients were all significantly improved. Sixty-six percent of
      all LDL values were at goal as were 77% of HDL and 62% of triglyceride (NCEP-II
      criteria). Sixty-two percent of LDL values in coronary artery disease patients
      were at goal contrasted to a reported range of 9.6%-71%. Life-style changes made
      significant differences in the percentage of patients at lipid goals. In
      postprogram follow-up there were significant differences between LTI and STI
      patients. The LTI patients did much better in improving lipid levels at
      postprogram follow-up than did STI patients. These results demonstrate the
      importance of making life-style changes as well as the importance of intensive
      efforts in achieving meaningful and lasting change.

PMID- 16895160
TI  - Retrospective analyses of the reading development of grade 4 students with
      reading disabilities: risk status and profiles over 5 years.
AB  - This study presents a longitudinal examination of the development of reading and
      reading-related skills of 22 Grade 4 children identified as having reading
      disabilities (RD) who had been followed since kindergarten. The analyses were
      conducted to investigate the patterns of emergence of RD as well as reading
      ability and risk status across the 5 years. The findings of the study are
      presented with an examination of the trajectories of the children with RD as
      compared to Grade 4 typical readers (matched for grade, gender, language status,
      and school) with a similar profile on literacy skills in kindergarten. The
      results demonstrate the heterogeneous nature of the trajectory of RD in school
      age children; although many of the children with RD were at risk in kindergarten,
      there was a subsample who did not demonstrate reading and phonological
      difficulties until the third and fourth grades.

PMID- 16895162
TI  - Timothy Burns Norbeck. Executive Director Connecticut State Medical Society 1977
      2006.

PMID- 16895163
TI  - Semi-annual meeting of the house of delegates. 1956.

PMID- 16895164
TI  - [Introduction: Seeing the forest as well as the tree].

PMID- 16895165
TI  - [Epidemiology of hypertension].

PMID- 16895166
TI  - [Renin-angiotensin system].

PMID- 16895167
TI  - [Role of renin-angiotensin system in cardiovascular remodeling].

PMID- 16895168
TI  - [Cardiovascular action of aldosterone].

PMID- 16895169
TI  - [Tissue angiotensin II generating system].

PMID- 16895170
TI  - [Angiotensin II and superoxide production].

PMID- 16895171
TI  - [AII and inflammation].

PMID- 16895172
TI  - [Circadian variations in gene expression of renin-angiotensin system].

PMID- 16895173
TI  - [Role of kallikrein-kinin system in blood pressure regulation].

PMID- 16895174
TI  - [Salt excess].

PMID- 16895176
TI  - [Endothelin].

PMID- 16895175
TI  - [Circulatory vasoactive substances and pathophysiology of hypertension].

PMID- 16895177
TI  - [Significance of natriuretic peptides and their receptors].

PMID- 16895178
TI  - [Arachidonate metabolites].

PMID- 16895179
TI  - [Salusin].

PMID- 16895181
TI  - [Adiponectin].

PMID- 16895180
TI  - [Prostasin].

PMID- 16895182
TI  - [Leptin].

PMID- 16895183
TI  - [Endogenous digitalis-like factor].

PMID- 16895184
TI  - [G protein signaling and hypertension].

PMID- 16895185
TI  - [Ion channel and blood pressure].

PMID- 16895186
TI  - [Hypertension and intracellular Ca2+ signalling].

PMID- 16895187
TI  - [Oxidative stress].

PMID- 16895188
TI  - [Regulatory mechanisms of cardiovascular remodeling in hypertension].

PMID- 16895189
TI  - [Endothelium-derived hyperpolarizing factor and endothelium dysfunction].

PMID- 16895190
TI  - [EDRF].

PMID- 16895191
TI  - [Roles of reactive oxygen species in vascular endothelial dysfunction].

PMID- 16895192
TI  - [Nitric oxide].

PMID- 16895194
TI  - [Genetically-engineered model animals].

PMID- 16895193
TI  - [Insulin resistance].

PMID- 16895195
TI  - [Genetic dissection of the renin-angiotensin system].

PMID- 16895196
TI  - [Hypertensive organ injuries in spontaneously hypertensive rats given N(G)-nitro
      L-arginine methyl ester].

PMID- 16895197
TI  - [Development of animal models for the metabolic syndrome with hypertension].

PMID- 16895198
TI  - [Renin gene and hypertension].

PMID- 16895199
TI  - [Angiotensin II type 1 receptor gene].

PMID- 16895200
TI  - [ALDH2].

PMID- 16895201
TI  - [Insulin receptor gene].

PMID- 16895203
TI  - [beta-Adrenergic receptor gene].

PMID- 16895202
TI  - [Low density lipoprotein receptor gene].

PMID- 16895204
TI  - [Leptin gene and leptin receptor gene].

PMID- 16895205
TI  - [Endothelin-1 gene].

PMID- 16895206
TI  - [G protein genes and hypertension].

PMID- 16895207
TI  - [Endothelial nitric oxide synthase gene and hypertension].

PMID- 16895208
TI  - [Atrial natriuretic peptide gene].

PMID- 16895209
TI  - [CRLR (calcitonin-receptor-like receptor) gene].

PMID- 16895211
TI  - [Angiotensin-converting enzyme gene polymorphism].

PMID- 16895210
TI  - [Endothelial cell growth inhibitory gene].

PMID- 16895212
TI  - [Angiotensinogen gene polymorphism].

PMID- 16895214
TI  - [Beta3-adrenergic receptor gene polymorphism].

PMID- 16895215
TI  - [NOS gene polymorphism].

PMID- 16895213
TI  - [Guanine nucleotide-binding protein beta 3 subunit (GNB3) gene polymorphism].

PMID- 16895216
TI  - [Protective effect of ARB on vascular diseases].

PMID- 16895217
TI  - [PPARgamma-activating properties of angiotensin receptor blockers].

PMID- 16895219
TI  - [Antiinflammatory action of angiotensin receptor blocker].

PMID- 16895218
TI  - [Inhibition of platelet aggregability by ARB].

PMID- 16895220
TI  - [Tumor suppressive effect].

PMID- 16895221
TI  - [Anti-atherosclerotic effect].

PMID- 16895222
TI  - [Cerebroprotection with calcium channel blockers].

PMID- 16895223
TI  - [Anti-oxidative effects of anti-hypertensive drugs].

PMID- 16895224
TI  - [Basic research for cardiovascular regeneration].

PMID- 16895225
TI  - [Basic research for renal regeneration].

PMID- 16895226
TI  - [Gene therapy for hypertension].

PMID- 16895227
TI  - [Future directions for antihypertensive drugs].

PMID- 16895228
TI  - [Genomic drug discovery of vascular remodeling].

PMID- 16895229
TI  - [Trend of research and development of antihypertensive agents].

PMID- 16895230
TI  - [Molecular studies on symbiosis of root nodule bacteria with Lotus japnicus].

PMID- 16895231
TI  - [Plant and fungal signalling molecules in the arbuscular mycorrhizal symbiosis].

PMID- 16895232
TI  - [Molecular genetics of signal perception and transduction in plant-microbe
      symbioses].

PMID- 16895234
TI  - [Rhizobial networks for symbiosis with legumes].

PMID- 16895235
TI  - [Genome analysis and resource development of Lotus japonicus].

PMID- 16895233
TI  - [Host legume genes required for symbiotic nitrogen fixation].

PMID- 16895237
TI  - [DNA replication machinery active at around 100 degrees C].

PMID- 16895236
TI  - [Origin and properties of the germ cell lineage in mice].

PMID- 16895238
TI  - Will trusts self-assess honestly?

PMID- 16895239
TI  - The health service is squandering our planet's resources.

PMID- 16895240
TI  - The reality of redundancy. Interview by Adrian O'Dowd.

PMID- 16895241
TI  - Giving pain relief.

PMID- 16895242
TI  - Speaking out for women with postnatal depression: a new role combining health
      visiting, mental health and management. Interview by Emma Vere-Jones.

PMID- 16895244
TI  - Obstetric fistula.

PMID- 16895243
TI  - Implications of the latest NICE Parkinson's disease guidance.
AB  - This month sees the release of new NICE best practice guidance for healthcare
      professionals caring for people with Parkinson's disease. The variety and
      severity of symptoms that affect people with Parkinson's result in significant
      disability and present a unique set of challenges for nurses.

PMID- 16895245
TI  - Resuscitation skills - part five: precordial thump.

PMID- 16895246
TI  - Understanding and critiquing qualitative research papers.
AB  - This article, the last in a series on research, examines the steps involved in
      qualitative research before introducing more terminology regarding the different
      approaches to qualitative studies. The process of evaluating qualitative research
      is explored by using an evaluative framework to further explain some of the
      terminology that researchers use.

PMID- 16895247
TI  - Lidocaine for surface anaesthesia.

PMID- 16895248
TI  - Designing and implementing an intravenous therapy book.
AB  - This article describes how a workbook for IV drug therapy for nurses was designed
      and implemented in the Royal United Hospital Bath NHS Trust.

PMID- 16895249
TI  - Perceptions of critical care outreach within a network.
AB  - AIM: The purpose of this study was to establish healthcare professionals'
      perceptions of critical care outreach. METHOD: A multi-site survey approach was
      used to collect qualitative data. RESULTS: Most respondents felt that outreach
      assisted with patient care by enabling the admission and smooth discharge to and
      from the critical care units and providing useful education and training that
      changed practice. Respondents also thought that the audits undertaken by the
      outreach teams benefited patient care. CONCLUSION: Overall, outreach was
      considered by healthcare professionals to enhance patient care and improve
      practice.

PMID- 16895250
TI  - A framework for your development.

PMID- 16895251
TI  - Does "idiopathic" REM sleep behavior disorder exist?

PMID- 16895252
TI  - Sleep-related eating disorder and night eating syndrome: sleep disorders, eating
      disorders, or both?

PMID- 16895253
TI  - The U-shaped association between sleep and health: the 2 peaks do not mean the
      same thing.

PMID- 16895255
TI  - The prevalence of multiple sleep-onset REM periods in a population-based sample.
AB  - STUDY OBJECTIVE: The presence of 2 or more sleep-onset rapid eye movement periods
      (SOREMPs) on a Multiple Sleep Latency Test (MSLT) has been used as 1 of the
      criteria for the diagnosis of narcolepsy and is thought to be specific to this
      disorder. However, previous studies have shown the prevalence of SOREMPS in
      healthy volunteers and apneic patients to be higher than expected. The present
      study determined the prevalence of 2 or more SOREMPs in a representative sample
      of the population from southeast Michigan and investigated potential associations
      with other sleep-related variables. DESIGN: Cross-sectional laboratory-based
      analysis. SETTINGS: Sleep disorders clinic. PARTICIPANTS: Population-based
      sample. INTERVENTIONS: N/A. MEASUREMENTS: A population-based sample of 333
      subjects was assessed by nocturnal polysomnography and daytime MSLT (5 naps), and
      an additional 206 subjectively sleepy people were also assessed (total = 539).
      Sample demographics were comparable to the 2000 census. Epworth Sleepiness Scale
      scores were also determined. Groups were formed based on a median split of each
      sleep variable (Epworth Sleepiness Scale, MSLT, total sleep time from nocturnal
      polysomnography) for comparisons of SOREMPs in each group. RESULTS: The
      prevalence of 2 or more SOREMPs was 3.9%. Only mean sleep latency on the MSLT was
      a discriminator for the presence of 2 or more SOREMPs (short latency = 6.3%, long
      latency = 1.9%, p < .05). Among the subjects who had an MSLT of 5 minutes or less
      (an indicator of a pathologic level of sleepiness), 9.5% had 2 or more SOREMPS.
      CONCLUSIONS: The overall prevalence of 2 or more SOREMPs in our sample is 3.9%.
      Interestingly, of the variables assessed (MSLT, Epworth Sleepiness Scale, and
      total sleep time from nocturnal polysomnography), objective sleepiness, as
      determined by the MSLT, was the only measure significantly associated with 2 or
      more SOREMPs. Therefore, subpopulations with excessive sleepiness (eg, shift
      workers, young adults, patients with apnea) are likely to have a greater
      prevalence of SOREMPs.

PMID- 16895254
TI  - Correlates of long sleep duration.
AB  - STUDY OBJECTIVE: Sleeping more than 7 to 8 hours per day has been consistently
      associated with increased mortality. Whether this association is causal and what
      pathways explain this association are unknown. We sought to identify factors that
      could potentially explain the association between long sleep and mortality.
      DESIGN: Cross-sectional epidemiologic survey. PARTICIPANTS: Middle-aged women (n
      = 60,028) participating in the Nurses Health Study II who reported a habitual
      sleep duration of 7 hours or more. RESULTS: Multiple sclerosis (odds ratio [OR] =
      3.7, 95% confidence interval [3.0-4.5]), antidepressant use (OR = 3.1, [2.9
      3.3]), benzodiazepine use (OR = 3.0 [2.6-3.3]), and systemic lupus erythematosus
      (OR = 2.9, [2.3-3.6]) were the factors most strongly associated with prolonged
      sleep. Combining these data with prevalence information and a range of plausible
      associations with mortality, the confounding rate ratio was estimated. This
      parameter is the ratio of the unadjusted long sleep-mortality rate ratio to the
      rate ratio adjusted for the factor and measures the extent that the factor can
      alter the long sleep-mortality association, either through confounding or as a
      causal intermediate. Based on this parameter, psychiatric and socioeconomic
      factors have the greatest potential to influence the long sleep-mortality
      relationship. Assuming each factor doubles mortality risk, the confounding rate
      ratios for depression, antidepressant use, and unemployment were 1.10, 1.18, and
      1.12. Lesser influential factors were benzodiazepine use, poverty, low societal
      status, sedentary lifestyle, and obesity. CONCLUSION: Depression and low
      socioeconomic status are strong candidates for producing the statistical
      association between long sleep and mortality, either as confounders or as causal
      intermediates. Future causal research on the effects of long sleep should include
      a detailed assessment of psychiatric disease and socioeconomic status.

PMID- 16895256
TI  - Snoring and vascular risk factors and disease in a low-risk Chinese population:
      the Guangzhou Biobank Cohort Study.
AB  - STUDY OBJECTIVE: Snoring is a common condition, but data describing the
      relationship between snoring and vascular disease is very limited in Asian
      populations. We therefore describe the association between snoring and vascular
      disease and associated risk factors. DESIGN: Cross-sectional study of baseline
      data from the Guangzhou Biobank Cohort Study. SETTING: Community-based elderly
      association from Guangzhou, China. PARTICIPANTS: 10413 Chinese subjects (50-85
      years of age). MEASUREMENTS: Self-reported snoring status and frequency and
      frequency of daytime tiredness were collected by questionnaire, as were
      demographic and socioeconomic data, disease histories, and potential confounders,
      such as smoking and alcohol consumption. Anthropometry, blood pressure, and
      fasting glucose and lipid profile were also measured. RESULTS: Self-reported
      snoring frequency was identified in 8325 (80.0%) subjects, with 51.6% reporting
      that they snored, of whom 15.5% were daily snorers. Increasing prevalence of
      snoring showed a clear positive relationship with cardiovascular risk factors,
      including age, obesity, blood pressure, and lipid levels (p < .001 for all). The
      prevalence of self-reported vascular-disease history was low but significantly
      associated with increasing snoring frequency. Logistic regression showed that
      snoring frequency was an independent predictor of vascular-disease history (odds
      ratios [95% confidence intervals] 1.68 [1.32-2.13] for daily snorers compared
      with the never-snorer reference group), of the metabolic syndrome (2.16 [1.88
      2.49]) and each of its components (hypertension [1.37 (1.20-1.56)], and of
      dyslipidemia [1.22 (1.07-1.40)], central obesity [2.39 (2.08-2.76)], and diabetes
      [1.30 (1.09-1.56)]) after adjustment for potential confounders. CONCLUSION:
      Increasing snoring frequency was associated with an increasing prevalence of risk
      factors and self-reported vascular disease. Snoring may a useful marker for
      increased risk of vascular disease.

PMID- 16895257
TI  - Physical examination: Mallampati score as an independent predictor of obstructive
      sleep apnea.
AB  - STUDY OBJECTIVE: To assess the clinical usefulness of the Mallampati score in
      patients with obstructive sleep apnea. Mallampati scoring of the orophyarynx is a
      simple noninvasive method used to assess the difficulty of endotracheal
      intubation, but its clinical usefulness has not been validated in patients with
      sleep-disordered breathing. DESIGN: Prospective multivariate assessment of a
      predictor variable. SETTING: The UCSF Sleep Disorders Center. PATIENTS OR
      PARTICIPANTS: One hundred thirty-seven adult patients who were evaluated for
      possible obstructive sleep apnea. INTERVENTIONS: Prospective determination of the
      Mallampati score, assessment of other variables for multivariate analysis, and
      subsequent overnight polysomnography. MEASUREMENTS AND RESULTS: The Mallampati
      score was an independent predictor of both the presence and severity of
      obstructive sleep apnea. On average, for every 1-point increase in the Mallampati
      score, the odds of having obstructive sleep apnea (apnea-hypopnea index> or = 5)
      increased more than 2-fold (odds ratio [per 1-point increase] = 2.5; 95%
      confidence interval: 1.2-5.0; p = .01), and the apnea-hypopnea index increased by
      more than 5 events per hour (coefficient = 5.2; 95% confidence interval: 0.2-10;
      p = .04). These results were independent of more than 30 variables that reflected
      airway anatomy, body habitus, symptoms, and medical history. CONCLUSION: Our
      results indicate that Mallampati scoring is a useful part of the physical
      examination of patients prior to polysomnography. The independent association
      between Mallampati score and presence and severity of obstructive sleep apnea
      suggests that this scoring system will have practical value in clinical settings
      and prospective studies of sleep-disordered breathing.

PMID- 16895258
TI  - Morphologic analyses of mandible and upper airway soft tissue by MRI of patients
      with obstructive sleep apnea hypopnea syndrome.
AB  - STUDY OBJECTIVES: To evaluate the morphological features of the mandible and the
      volume of the upper airway soft tissues in determining the anatomical risk
      factors for the upper airway in Japanese male patients with obstructive sleep
      apnea hypopnea syndrome (OSAHS). METHODS: Five morphological parameters of the
      mandible at the mandibular base plane and three volumetric parameters of the
      upper airway soft tissue were analyzed using three-dimensional (3D) magnetic
      resonance imaging software in 31 OSAHS and 20 controls. RESULTS: There were no
      significant differences between the two groups in mandibular internal width (the
      distance between the internal right and left gonia [IRG and ILG]) and mandibular
      bony thickness. However, the patients with OSAHS had a significantly wider
      mandibular divergence (the angle between the spina mentalis (SM)- IRG line and SM
      ILG line), a smaller mandibular internal length (the perpendicular distance from
      SM to the RG- LG line), and a smaller area than the normal subjects at the
      mandibular base plane. There were no significant differences in these
      morphological parameters for the mandible between obese and nonobese OSAHS
      patients. The volumes of the tongue, soft palate, and lateral pharyngeal walls
      were not significantly different between the OSAHS and the control groups.
      CONCLUSIONS: Japanese male OSAHS patients had specific anatomical features in the
      bottom part of the mandible; however, obesity seemed to be a less significant
      risk factor. Investigators and clinicians must realize that ethnicity may modify
      the effects of obesity and abnormal craniofacial anatomy as risk factors for the
      pathogenesis of OSAHS.

PMID- 16895259
TI  - Excessive daytime sleepiness in Parkinson disease: a SPECT study.
AB  - STUDY OBJECTIVES: The underlying pathologic mechanism of excessive daytime
      sleepiness (EDS) in Parkinson disease and the relative contributions of brain
      function to this process are poorly understood. We compared brain perfusion
      images between patients with Parkinson disease and EDS and those without EDS
      using n-isopropyl-p-1231 iodoamphetamine single photon emission computed
      tomography. DESIGN: Clinical study. SETTING: Sumitomo Hospital. PATIENTS:
      Thirteen patients with Parkinson disease with EDS (EDS group) and 27 patients
      with Parkinson disease without EDS (no-EDS group) were studied. Whether or not
      each case had EDS was determined according to the response to the Epworth
      Sleepiness Scale: patients with an Epworth Sleepiness Scale score > or = 10 were
      included in the EDS group, and patients with an Epworth Sleepiness Scale score <
      or = 9 were included in the no-EDS group. MEASUREMENTS AND RESULTS: There were
      significant hypoperfusions in the left parietal and temporal association cortex
      in the EDS group. In the multivariable logistic regression model, attention and
      decreased regional cerebral blood flow of the left parietal association cortex
      and right caudate and increased regional cerebral blood flow of the right
      thalamus were the independent and significant factors. CONCLUSIONS: The cortical
      hypofunction relative to hyperfunction of the brain stem may relate to EDS in
      Parkinson disease. This is the first imaging study about EDS in Parkinson
      disease, and further studies are required.

PMID- 16895260
TI  - A preliminary fluorodeoxyglucose positron emission tomography study in healthy
      adults reporting dream-enactment behavior.
AB  - STUDY OBJECTIVES: To test the hypothesis that healthy adults reporting dream
      enactment behavior (DEB+) have reduced cerebral metabolic rate for glucose
      (CMRgl) in regions preferentially affected in patients with dementia with Lewy
      bodies (DLB). DESIGN: Automated brain-mapping algorithms were used to compare
      regional fluorodeoxyglucose (FDG) positron emission tomography (PET) measurements
      from previously evaluated DEB cases and controls. SETTING: Tertiary-care academic
      medical centers. PARTICIPANTS: Seventeen cognitively normal patients with DEB+
      and 17 control subjects (DEB-) who were individually matched for age (59 +/- 11
      years), education level (16 +/- 4 years), sex (67% women), body mass index (26 +/
      4.8 kg/m2), first-degree relative with dementia (85%), and proportion of
      apolipoprotein E (APOE) e4 carriers (13 e4 carriers, 4 noncarriers).
      INTERVENTIONS: FDG-PET. MEASUREMENTS AND RESULTS: DEB was associated with
      significantly lower CMRgl in several brain regions known to be preferentially
      affected in both DLB and Alzheimer disease (parietal, temporal, and posterior
      cingulate cortexes) and in several other regions, including the anterior
      cingulate cortex (p < .001, uncorrected for multiple comparisons). The DEB
      associated CMRgl reductions were significantly greater in the APOE e4 noncarriers
      than in the carriers. CONCLUSIONS: These preliminary findings suggest that
      cognitively normal persons with DEB have reduced CMRgl in brain regions known to
      be metabolically affected by DLB, supporting further study of DEB as a possible
      risk factor for the development of DLB.

PMID- 16895261
TI  - Interictal, potentially misleading, epileptiform EEG abnormalities in REM sleep
      behavior disorder.
AB  - STUDY OBJECTIVES: To examine the implications of interictal epileptiform
      abnormalities (IEA) in idiopathic REM-sleep behavior disorder (RBD), particularly
      the risk of misdiagnosing RBD episodes as epileptic nocturnal seizures. DESIGN:
      Observational analysis and review. SETTING: Tertiary sleep center. PATIENTS:
      Thirty patients (28 men; mean age 66.3 +/- 7.5 years) referred to our sleep unit
      for a definite diagnosis of nocturnal sleep-related motor and behavioral
      paroxysmal episodes. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: All the
      patients were found to be affected by idiopathic RBD according to standard
      clinical and videopolysomnographic criteria. IEA(sporadic, fronto-temporal sharp
      waves) were detected in 8 subjects (26.6%) during routine electroencephalogram
      and/or nocturnal in-lab videopolysomnography with extended EEG montages. In 2 of
      these 8 patients, IEA occurred during REM sleep. CONCLUSIONS: When only the
      clinical history is considered, RBD episodes may be confused with nocturnal
      epileptic focal seizures. The presence of IEA either on routine awake
      electroencephalograms, or during sleep electroencephalograms, may add support for
      a diagnosis of epileptic nocturnal seizures. Our data show that IEA may occur in
      wake and sleep (non rapid eye movement and rapid eye movement sleep) tracings of
      subjects with episodes of idiopathic RBD. However full-night extended
      electroencephalogram montages and polysomnography recording of an episode proved
      useful in establishing a definite diagnosis of RBD in these potentially
      misleading cases. Comparison of the patients' demographic data and RBD features
      revealed no differences between RBD with IEA and without IEA. On this basis-and
      given that these abnormalities have also been described in elderly people with
      wakefulness-related nonepileptic disorders-IEA in RBD could simply be interpreted
      as a nonspecific phenomenon, probably related to brain aging.

PMID- 16895262
TI  - Sodium oxybate improves excessive daytime sleepiness in narcolepsy.
AB  - STUDY OBJECTIVES: To assess the effectiveness of sodium oxybate therapy,
      modafinil therapy and the combination of the two for excessive daytime sleepiness
      in narcolepsy patients previously taking modafinil. DESIGN: Double-blind, placebo
      controlled, multicenter study. SETTING: Forty-four sites in the United States,
      Canada, the Czech Republic, France, Germany, the Netherlands, Switzerland, and
      the United Kingdom. PARTICIPANTS: Two hundred seventy- adult patients with
      narcolepsy taking 200 to 600 mg of modafinil daily for the treatment of excessive
      daytime sleepiness. INTERVENTIONS: Patients received unchanged doses of modafinil
      (with sodium-oxybate placebo) during a 2-week baseline phase. Following a
      baseline polysomnogram and Maintenance of Wakefulness Test, they were randomly
      assigned to 1 of 4 treatment groups: sodium-oxybate placebo plus modafinil
      placebo, sodium oxybate plus modafinil placebo, modafinil plus sodium-oxybate
      placebo, or sodium oxybate plus modafinil. Sodium oxybate was administered as 6 g
      nightly for 4 weeks and was then increased to 9 g nightly for 4 additional weeks.
      The primary efficacy measure was the Maintenance of Wakefulness Test; secondary
      measures included the Epworth Sleepiness Scale, diary recordings, and the
      Clinical Global Impression-change scale. RESULTS: Following the switch from
      modafinil to placebo, the mean average daytime sleep latency on the Maintenance
      of Wakefulness Test decreased from 9.74 minutes at baseline to 6.87 minutes after
      8 weeks (p < .001). In the sodium-oxybate group, there was no decrease in sleep
      latency, suggesting that this drug was as efficacious in treating the excessive
      daytime sleepiness as the previously administered modafinil. In contrast, the
      sodium-oxybate/modafinil group demonstrated an increase in daytime sleep latency
      from 10.43 minutes to 13.15 minutes (p < .001), suggesting that this combination
      of drugs produced an additive effect. The sodium-oxybate group also demonstrated
      a decrease in median average Epworth Sleepiness Scale scores, from 15 to 12.0,
      whereas the sodium-oxybate/modafinil group decreased from 15.0 to 11.0 (for both,
      p < .001). The Clinical Global Impression-Change scale demonstrated similar
      results. CONCLUSIONS: Sodium oxybate and modafinil are both effective for
      treating excessive daytime sleepiness in narcolepsy, producing additive effects
      when used together. Sodium oxybate is beneficial as both monotherapy and as
      adjunctive therapy for the treatment of excessive daytime sleepiness in
      narcolepsy.

PMID- 16895263
TI  - Nocturnal eating: sleep-related eating disorder or night eating syndrome? A
      videopolysomnographic study.
AB  - STUDY OBJECTIVES: To describe the clinical and videopolysomnographic
      characteristics of nocturnal eating episodes in sleep-related eating disorder.
      DESIGN: Descriptive study of outpatients prospectively enrolled in 2 sleep
      centers. SETTING: Videopolysomnographic recordings done in the sleep laboratory.
      PATIENTS: Thirty-five consecutive drug-free patients with nocturnal eating.
      INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Clinical interviews disclosed
      abnormal compulsory nocturnal eating episodes in all patients associated with a
      clinical report of sleepwalking (in 1), somniloquy (in 5), restless legs syndrome
      (in 8), and periodic limb movements during sleep (in 4). Videopolysomnography
      documented 45 episodes of nocturnal eating in 26 patients. Eating always occurred
      after complete awakenings from non-rapid eye movement sleep and only in 1 patient
      from REM sleep and was characterized by electroencephalographic alpha activity
      with no dissociated features of state-dependent sleep variables. Patients
      interviewed during the eating episodes were fully conscious and remembered the
      events the next day. Pathological periodic limb movements during sleep index was
      recorded in 22 and restless legs syndrome dyskinesias in 5 patients. Recurring
      chewing and swallowing movements during sleep were a feature in 29 patients,
      associated in about half of the events with electroencephalographic arousals.
      CONCLUSIONS: In our patients, eating episodes occurred with normal consciousness
      and recall. Chewing or swallowing movements during sleep occurred frequently,
      resembling rhythmic masticatory-muscle activity in bruxism patients. The presence
      of periodic limb movements during sleep and chewing activity, the reported
      efficacy of dopaminergic medications, and the compulsory food-seeking behavior
      all argue for a dopaminergic dysfunction underlying the pathogenesis of sleep
      related eating disorder.

PMID- 16895264
TI  - Characterizing impaired functional alertness from diphenhydramine in the elderly
      with performance and neurophysiologic measures.
AB  - STUDY OBJECTIVES: Psychometric task performance measures can be highly sensitive
      to manipulations that impair functional alertness in young adults; such measures
      have been shown to be less sensitive to reduced alertness in older adults. The
      purpose of this study is to determine whether neurophysiologic measures can aid
      in the detection and characterization of impairments in functional alertness in
      the elderly. DESIGN: Double-blind, placebo-controlled, counter-balanced,
      crossover study. SETTING: Research laboratory. PARTICIPANTS: Twelve healthy older
      adults (62-75 years of age). INTERVENTIONS: Diphenhydramine, 50 mg. MEASUREMENTS
      AND RESULTS: Behavioral performance and electroencephalogram measures were
      obtained while participants completed spatial working memory and word recognition
      episodic memory tasks in a baseline interval before drug ingestion and in 4
      hourly test intervals following drug ingestion. Relative to placebo,
      diphenhydramine had marginal effects on task performance yet was effective in
      reducing alertness, as evidenced by subjective ratings and objective
      neurophysiologic (electroencephalogram) markers. Diphenhydramine significantly
      reduced the amplitude of alertness-sensitive event-related potentials recorded
      during working memory task performance, including the N160 and P300. It also
      affected neurophysiologic processes underlying episodic memory, as evidenced by a
      reduction in the difference in event-related potentials between old and new words
      in the word recognition task. Discriminant analyses incorporating
      neurophysiologic measures showed that the time course of the central effects of
      diphenhydramine in older subjects was similar to that previously observed in
      young adults. CONCLUSIONS: These results demonstrate that diphenhydramine has
      adverse neurocognitive effects in elderly individuals and highlights the utility
      of incorporating direct measures of brain function into assessments of functional
      alertness.

PMID- 16895265
TI  - A taxonomic analysis of sleep stages.
AB  - STUDY OBJECTIVES: To study the structure of human sleep at the level of sleep
      stages. We applied taxonomic statistics to detect significant configurations
      (types) of different physiologic variables and their relationship to sleep
      stages. DESIGN AND STATISTICS: Polygraphic sleep recordings from 32 subjects
      (normal sleepers as well as patients with insomnia, sleep apnea, or narcolepsy; n
      = 8 per group) were visually scored and submitted to a configural frequency
      analysis. The configural frequency analysis was computed with 3 continuous input
      variables: an electroencephalogram parameter, which represents the point of
      gravity of the EEG frequency distribution; the alpha slow-wave index, and the
      Rest Index, based on the presence or absence of phasic electromyographic
      activity. These variables were dichotomized for further analysis. The combination
      of 2 levels ( + or -) and 3 variables resulted in 2(3) patterns ( +++ to - - - ).
      The configural frequency analysis is a nonparametric X2-type multivariate
      statistic that identifies significant patterns or types. RESULTS: Each sleep
      stage contained 3 or 4 types. For non-rapid eye movement sleep stages 2, 3, and
      4, types overlapped, whereas there was no overlap of types between stages 1 and
      2. Types of rapid eye movement sleep did not overlap with those from stages 2, 3,
      and 4 but did overlap with wake and stage 1 types. The majority of observed types
      were significant in all 4 groups of subjects. CONCLUSIONS: Sleep stages appear to
      be less homogenous than rule-based sleep scoring would suggest. Types were either
      restricted to one stage or overlapped with neighboring stages.

PMID- 16895266
TI  - Effect of voluntary attention on auditory processing during REM sleep.
AB  - STUDY OBJECTIVES: The study investigates whether there is an effect of voluntary
      attention to external auditory stimuli during rapid eye movement (REM) sleep in
      humans by measuring event-related potentials (ERPs). DESIGN: Using a 2-tone
      auditory-discrimination task, a standard 1000-Hz tone and a deviant 2000-Hz tone
      were presented to participants when awake and during sleep. In the ATTENTIVE
      condition, participants were requested to detect the deviant stimuli during their
      sleep whenever possible. In the PASSIVE sleep condition, participants were only
      exposed to the tones. ERPs were measured during REM sleep and compared between
      the 2 conditions. SETTING: All experiments were conducted at the sleep laboratory
      of Hiroshima University. PARTICIPANTS: Twenty healthy university student
      volunteers. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: In the tonic period of
      REM sleep (the period without REM), P200 and P400 were elicited by deviant
      stimuli, with scalp distributions maximal at central and occipital sites,
      respectively. The P400 in REM sleep showed larger amplitudes in the ATTENTIVE
      condition, whereas the P200 amplitude did not differ between the 2 conditions. No
      effects on ERPs due to attention were observed during stage 2 sleep. CONCLUSIONS:
      The instruction to pay attention to external stimuli during REM sleep influenced
      the late positive potentials. Thus electrophysiologic evidence of voluntary
      attention during REM sleep has been demonstrated.

PMID- 16895267
TI  - Liver transplant in Hawai'i: over a hundred cases.
AB  - One hundred and two liver transplants have been performed since the program's
      inception in Hawai'i in 1993. Viral hepatitis continues to be the primary
      indication for liver transplant, though hepatocellular cancer is involved in
      23.5% of cases. One, 3 and 5-year patient survival rates have been 88%, 79%, and
      74% respectively which is comparable to mainland centers and national data.

PMID- 16895268
TI  - Synchronous liver cancers: A rare tumor combination in an elderly Japanese woman.
AB  - Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) may occur
      simultaneously in a person with primary liver cancer However HCC and CC arising
      from separate foci is extremely rare. This is a case presentation of a 66-year
      old woman with primary combined HCC-CC, who had no risk factors for either tumor.

PMID- 16895269
TI  - Valve replacement in endocarditis: setting limits in noncompliant intravenous
      drug abusers.
AB  - An intravenous (IV) drug abuser underwent repeated valve replacements because of
      recurrent infective endocarditis. Is it ethically permissible to withhold valve
      surgery in a recalcitrant, noncompliant IV drug abuser? We believe so, and in our
      analysis, discuss the principles of futility, rationing, personal responsibility,
      and justice. Because of her continued drug abuse, the patient is responsible and
      accountable for the medical consequences. The consequences are that physicians
      will not be able to provide her with beneficial treatments without
      disproportionate harm, and that society will no longer be able to provide
      resources for her treatment without unfairly jeopardizing the availability of
      resources for other members of society. Although valve surgery does not
      constitute futile treatment, maximizing and egalitarian principles of societal
      justice support the withholding of such an expensive intervention. The patient
      should be jointly evaluated by the physician, social worker, and psychiatrist.
      The medical team will emphasize patient compliance and willingness to undergo
      drug rehabilitation, and will offer the first valve replacement. The recidivist
      abuser with demonstrable non-compliance who sustains a second episode of
      endocarditis need not be offered another valve. To avoid bedside rationing, we
      recommend the formulation of such a policy by nations and professional bodies.

PMID- 16895270
TI  - Trauma system development: crisis at our doorstep.

PMID- 16895271
TI  - Pacific Tracker (PacTrac): an interactive dietary assessment program at the CRCH
      website.

PMID- 16895272
TI  - Eosinophilic meningitis? Consider angiostrongyliasis.

PMID- 16895273
TI  - Preliminary results of bicalutamide monotherapy on biochemical failure of
      localized prostate cancer.
AB  - OBJECTIVES: To prospectively assess the efficacy and tolerability of bicalutamide
      monotherapy on biochemical failure of localized prostate cancer following total
      androgen deprivation (TAD) and 3D-conformal radiotherapy (3D-CRT). METHODS:
      Between January 1998 and January 2002, we prospectively evaluated 20 eligible
      patients with biochemical failure. All patients were initially treated with
      neoadjuvant TAD of 12 weeks before 3D-CRT (73.6 Gy at isocenter) and same regimen
      of TAD after completion of radiotherapy for 24 weeks in high-risk patients. We
      prescribed 150 mg/day bicalutamide monotherapy for 24 weeks in patients with
      biochemical failure according to American Society for Therapeutic Radiology and
      Oncology 1997 consensus definition. Primary end points were biochemical control
      (BC) and metastasis-free survival (MFS). RESULTS: Median follow-up was 28 months
      after biochemical failure date. At last visit, the median PSA level of all
      patients was 2.80 ng/dl while 1.28 ng/dl for nonmetastatic and 30.7 ng/dl for
      metastatic patients. BC was successfully obtained in five of them with only
      bicalutamide. Ten patients developed distant metastasis among 15 patients
      receiving salvage TAD. MFS was 55% at three years for all 20 patients. Temporary
      gynecomasty was observed in 11 patients as the only serious toxicity.
      CONCLUSIONS: Bicalutamide monotherapy seems to be a tolerable regimen for
      patients with biochemical failure following 3D-CRT, and TAD and may be effective
      in patients with low PSA levels at biochemical failure.

PMID- 16895274
TI  - Heart-type, fatty-acid binding protein can be a diagnostic marker in acute
      coronary syndromes.
AB  - OBJECTIVES: Chest pain is one of the most common complaints among patients
      admitted to emergency departments. Cardiac troponins, CK-MB and myoglobin, which
      are used routinely in the diagnosis of acute coronary syndrome (ACS), are not
      elevated in the initial hours of ACS--precluding their usefulness in the early
      diagnosis. The aim of this study is to determine the efficacy of H-FABP compared
      to myoglobin and CK-MB in the early diagnosis of ACS. METHODS: Sixty-seven
      patients with ACS were enrolled in the study. An initial blood sample was
      obtained for CK-MB, cTnT, myoglobin and H-FABP. At the fourth, eighth, and 12th
      hours, repeat ECGs and cardiac enzyme samples were obtained. H-FABP test was
      repeated at the fourth hour. RESULTS: H-FABP has sensitivity equal to that of CK
      MB and superior to that of myoglobin (97.6%, 96.7%, 85.4%, respectively) on the
      first hour. This trend extends to the fourth hour of myocardial injury as well. H
      FABP was more specific than CK-MB, myoglobin and troponin T at the first hour
      (38.5%, 34.6%, 34.6%, 23.1%, respectively), whereas its specificity at the fourth
      hour was equal to those of CK-MB and troponin T and exceeded that of myoglobin.
      CONCLUSIONS: It can be suggested that in patients with an initial diagnosis of
      ACS and within 20 hours from symptom onset, H-FABP levels may be measured. For
      this purpose, point-of-care H-FABP test may be utilized, which has the advantage
      of bedside testing and rapid test results.

PMID- 16895275
TI  - Race and medication adherence in Medicaid enrollees with type-2 diabetes.
AB  - OBJECTIVE: The association of medication adherence with race has been
      inadequately studied previously in type-2 diabetes patients. The study objective
      was to determine the association between race and medication adherence among type
      2 diabetes patients. METHODS: This was a retrospective cohort study, which
      compared medication adherence among different races of Medicaid insured patients
      with type-2 diabetes newly starting oral antidiabetic medication. A total of
      1,527 African-American patients newly starting antidiabetic medication between
      July 2001 and June 2002 were compared with 1,128 white patients and 514 patients
      of other race. Medication adherence was measured as medication possession ratio
      using prescription refill patterns. Multivariate regression analyses were used to
      determine the difference in adherence rates adjusting for other covariates.
      RESULTS: Medication adherence rate was significantly higher for whites [0.59
      (0.31)] as compared to African Americans [0.54 (0.31), (p<0.05)]. In multivariate
      analyses, the adherence rate of African-American patients was found to be
      significantly lower by 12% as compared to whites after adjusting for other
      covariates. Metformin users were associated with a 62% decrease in adherence rate
      as compared with the sulfonylureas group (p<0.05). CONCLUSION: The antidiabetic
      medication adherence was associated with race. Future research should investigate
      patient-related factors affecting medication adherence in type-2 diabetes
      patients.

PMID- 16895276
TI  - The use of missing birth record data as a marker for adverse reproductive
      outcomes: a geocoded analysis of birth record data.
AB  - Adverse reproductive outcomes (AROs) disproportionately affect black American
      infants and significantly contribute to the U.S. infant mortality rate. Without
      accurate understanding of AROs, there remains little hope of ameliorating infant
      mortality rates or eliminating infant health disparities. However, despite the
      importance of monitoring infant mortality rates and health disparities, birth
      record data quality is not assured. Racial disparities in the reporting of birth
      record data have been documented, and missing birth record data for AROs appears
      to be disproportionate. Due to the extent of missing birth record data,
      innovative strategies have been developed to evaluate relationships between
      maternal socioeconomic status (SES) and community-based ARO rates. Because
      addresses convey aggregate information about income level, education and
      occupation, ZIP codes, census tracts and census block-groups have been applied to
      geocoding efforts. The goals of this study are to: 1) analyze the extent of
      missing birth record data for New Jersey areas with high rates of an ARO (preterm
      birth), 2) evaluate associations between the extent of missing birth record data
      and other AROs, and 3) consider how geocoding strategies could be applied to
      provide a basis for understanding maternal SES risk factors and ARO resource
      allocation for at-risk communities.

PMID- 16895278
TI  - Assessing endoscopic colorectal screening adherence in an emergency department
      population.
AB  - OBJECTIVES: Colorectal cancer (CRC) has the second highest cancer-related
      mortality rate in the United States. However, CRC screening rates, particularly
      by endoscopy, are dismally low. The purpose of this study is to determine the
      factors associated with adherence to endoscopic screening using the emergency
      department (ED) population. METHODS: Structured interviews in English or Spanish
      were administered to 122 patients, aged > or =50 in the ED of an urban academic
      medical center. Questions focused on sociodemographic and medical factors,
      knowledge deficits and attitudes towards screening as well as psychosocial
      factors that may be associated with screening adherence. Compliance with current
      screening guidelines was measured by self-report. RESULTS: The population was
      sociodemographically diverse. There were significant differences across ethnic
      groups with regards to awareness and attitudes toward screening as well
      participation in screening. Age >65, Spanish language during the interview, white
      ethnicity and having a primary care physician were significant correlates of
      adherence to screening colonoscopy. Once decisional balance (conspros) was
      entered into the model, the other factors were no longer significant.
      Furthermore, physician referral was the strongest correlate of adherence to
      endoscopic screening. CONCLUSIONS: There are significant sociodemographic,
      medical and psychosocial barriers preventing CRC screening adherence in ED
      patients, yet the strongest correlate is physician referral. The ED encounter may
      serve as an opportunity to provide information and referral for CRC screening.

PMID- 16895277
TI  - Acceptance of pneumococcal vaccine under standing orders by race and ethnicity.
AB  - PURPOSE: To assess whether and how pneumococcal vaccine acceptance occurs after
      nurse recommendation varies by race/ethnicity. METHODS: We prospectively
      evaluated nurses' standing orders to assess and vaccinate high-risk patients in a
      general medicine practice. RESULTS: Of 370 adult patients surveyed (60%
      nonwhite), 78 (21%) declined vaccination following nurse recommendation, and 43
      (12%) persisted in declining after physician consultation. Three-hundred-twenty
      seven (88%) patients accepted vaccination: 292 (79%) accepted following nurse
      recommendation and 35 (9%) following physician consultation. African Americans
      (19%) were significantly more likely to decline compared with whites (8%) and
      Asians (5%) (P= 0.01). Reasons for refusal included believing vaccination was
      unnecessary (32%), fearing shots in general (21%), fearing vaccine-induced
      illness (26%) and wanting more informotion regarding the vaccine (9%).
      CONCLUSION: Standing orders, physicians' firm recommendations and addressing
      patients' vaccine-related concerns may reduce racial/ethnic disparities in
      vaccination.

PMID- 16895280
TI  - Utilization of the office, hospital and emergency department for adult sickle
      cell patients: a five-year study.
AB  - Sickle cell disease (SCD) is a hematological disorder that is manifested
      primarily by severe pain and chronic organ damage. Little normative data exists
      on what the usual healthcare utilization is of a population of SCD patients,
      especially adults. Our study analyzed the office, emergency department (ED) and
      hospital use data for 142 patients who received care for three consecutive years.
      Relationships between health service use, patient age, gender and sickle cell
      phenotype were described. Multivariate analyses studied relationships between
      demographic and clinical characteristics and levels of office, independent ED and
      inpatient encounters over a five-year period (1997-2001). We found female
      patients were older and had less ED and hospital admissions. The 20% highest
      inpatient utilizers accounted for 54% of the ED total visits, 52% of the ED
      independent visits, 54% of hospital bed days and 24% of office visits. The ED was
      a common place for utilization, with a mean of 7.4 visits per patient year, a
      third of which resulted in a hospital admission. The healthcare utilization of
      our adult sickle cell population is very complex, with a subset of our patients
      accounting for a majority of the resources used and female patients living longer
      but with less ED and hospital admissions.

PMID- 16895279
TI  - Bone mineral density-affecting genes in Africans.
AB  - BACKGROUND: We have recently reported the role of environmental exposure in the
      ethnic diversity of bone mineral density (BMD). Potential genetic difference has
      not been adequately assessed. PURPOSE: To determine allele frequencies of BMD
      affecting genes and their association with BMD in Africans. METHODS: Allele
      frequencies at 18 polymorphic sites in 13 genes that affect BMD in Asians and/or
      Caucasians were determined in 143 recent immigrants (55 men and 88 women, 18-51
      years of age) from sub-Saharan Sudan to the United States. Genetic association
      studies were performed. RESULTS: Among the 14 single-nucleotide polymorphisms
      (SNPs), 10 were significantly different in allele frequency between Sudanese and
      Asians, and 10 between Sudanese and Caucasians. Only the osteocalcin gene was not
      significantly different in allele frequency among Sudanese, Asians and
      Caucasians. Allele frequencies in the TGFB, COL1A1 and CSR genes were extremely
      low (<0.04) in the Sudanese. Frequencies of microsatellite alleles in four genes
      were significantly different among Sudanese, Asians and Caucasians. SNPs in the
      VDR and ERalpha genes were associated with BMD and/or BMC (bone mineral content)
      at several bone sites. CONCLUSIONS: Genetic difference may play a role in the
      ethnic diversity in BMD and/or BMC.

PMID- 16895281
TI  - Physical functioning in older blacks: an exploratory study identifying
      psychosocial and clinical predictors.
AB  - OBJECTIVES: The primary objective of this investigation was to examine the
      relationship between physical functioning and various clinical (pain intensity,
      pain locations, medications, comorbidities) and psychosocial (depression, locus
      of control) variables in a sample of older blacks. METHODS: Data were collected
      from community-dwelling black adults (N=247), with a mean age of 69.4 +/- 9.4
      years. Participants were recruited from several senior high-rise facilities
      located in an urban community in Baltimore, MD. A multivariate regression model
      was tested to determine the relationship between selected clinical, psychosocial
      and demographic characteristics, and physical functioning; and to assess the
      amount of unique variance in functional status accounted for by specific
      psychosocial, clinical and demographic indicators (independently and
      collectively). RESULTS: It was established that reporting more depressive
      symptoms (beta=0.18, p<0.05), multiple pain locations (beta=0.25, p<0.01) and
      pain intensity (beta=0.30, p<0.01) was a significant indicator of physical
      impairment and accounted for 36% of its variation. CONCLUSION: Identifying
      indicators of physical impairment is critical in providing baseline information
      on the functional well-being in older blacks. This emphasizes the need for
      further studies to rigorously examine the relationship between physical
      functioning, and clinical and psychosocial indicators within defined race and
      ethnic groups in order to develop data that provide meaningful comparisons
      between different race and ethnic groups.

PMID- 16895282
TI  - Depression and intelligence in patients with Parkinson's disease and deep-brain
      stimulation.
AB  - The goal of this study is to examine the association of depression with
      intelligence and education in patients with Parkinson's disease treated with
      bilateral subthalamic nucleus stimulation (STN-DBS). The literature has been
      contradictory concerning depression in Parkinson's disease patients. Some studies
      have shown less depression in Parkinson's disease patients with more education
      not treated with STN-DBS. Other recently published studies indicate that STN-DBS
      improves the depression associated with Parkinson's disease. No studies have
      examined the correlation of these factors with depression in Parkinson's disease
      patients treated with STN-DBS. We administered the Beck Depression Inventory
      (BDI) pre- and postoperatively to 21 Parkinson's disease patients (seven women,
      14 men, ages 49-75) who underwent STN-DBS. The postoperative scores of the lower
      50th percentile (n=8) of the Verbal Comprehensive Index of the Wechsler Adult
      Intelligence Scale (WAIS-III) decreased significantly (P=0.036), while the upper
      50th percentile (n=13) remained nearly constant (P=0.802). Furthermore, as the
      education increased from highschool to graduate level, patients demonstrated less
      improvement in depressive symptoms postoperatively. These findings suggest that
      Parkinson's disease patients with lower intelligence test scores and less
      education benefit more with regards to depressive symptomatology after STN-DBS
      than patients with higher scores and education.

PMID- 16895285
TI  - Clinical manifestations of sarcoidosis among inner-city African-American
      dwellers.
AB  - OBJECTIVES: To characterize clinical, radiographic and physiological features of
      sarcoidosis among African Americans residing in inner-city Chicago. METHODS: This
      is a retrospective review of medical records of 75 African Americans with biopsy
      proven sarcoidosis from internal medicine and pulmonary clinics at three inner
      city, acute care hospitals in Chicago. RESULTS: The number of organs involved was
      1.77 +/- 0.94 (mean +/- SD). The most common sites for tissue diagnosis were lung
      (49%), skin (19%) and lymph nodes (16%). Thirty-six (48%) patients had stage-2
      and -3 disease on chest x-ray. Electrocardiographic changes and ocular
      involvement were detected in 23% and 21% of patients, respectively. Nineteen
      (25%) patients had obstructive defect (FEV1 1.71 +/- 0.78 L/s), 15 (20%) had a
      restrictive defect [TLC 4.1 +/- 1.2 L (63.9 +/- 9.2% predicted)]. Three patients
      had both restrictive and obstructive defect. Forced vital capacity and FEV1
      declined by 0.26 L and 0.09 L/s per year, respectively, in patients with an
      obstructive defect. Most patients (91%) were treated with prednisone for 3.8 +/-
      3.9 years (range 0-20 years). CONCLUSIONS: African Americans with sarcoidosis
      residing in inner-city Chicago express a high rate of chronic progressive disease
      necessitating corticosteroid therapy. Further studies are warranted to elucidate
      the reasons underlying this paradigm.

PMID- 16895283
TI  - Safe pharmacologic treatment strategies for osteoarthritis pain in African
      Americans with hypertension, and renal and cardiac disease.
AB  - Arthritis is the leading cause of disability in the United States.
      Osteoarthritis, the most common form of arthritis, is a degenerative joint
      disease affecting both whites and African Americans similarly. African Americans
      have a high incidence rate of comorbidities, including hypertension,
      cardiovascular disease (CVD) risk factors and diabetes. Treatment of
      osteoarthritic pain in patients with comorbidities is often complicated by
      potential safety concerns. Traditional nonsteroidal antiinflammatory drugs
      (NSAIDs) and cyclooxygenase 2 (COX-2) specific NSAIDs have been shown to increase
      blood pressure in hypertensive patients taking antihypertensive medications.
      Patients with CVD risk factors taking low-dose aspirin for secondary prevention
      may be at increased risk for gastrointestinal bleeding with NSAIDs. Diabetics
      face an increased risk of renal complications. Because NSAIDs are associated with
      adverse renal effects, they should be used cautiously in patients with advanced
      renal disease. Acetaminophen is the most appropriate initial analgesic for
      African Americans with chronic osteoarthritic pain and concurrent hypertension,
      CVD risk factors or diabetes, and is recommended by the American College of
      Rheumatology as first-line treatment. Many of the adverse effects commonly
      associated with NSAIDs are not associated with acetaminophen. Safety concerns
      surrounding pharmacologic treatment of osteoarthritis in African Americans are
      reviewed.

PMID- 16895284
TI  - Radiotherapy in the management of Kaposi's sarcoma: comparison of 8 Gy versus 6
      Gy.
AB  - OBJECTIVE: To evaluate prospectively the efficacy of a single fraction of high
      dose radiotherapy in patients with Kaposi's sarcoma. PATIENTS: Between 1994 and
      2004, 47 patients with Kaposi's sarcoma were treated at Hacettepe University,
      Department of Radiation Oncology. Thirteen (28%) patients received chemotherapy
      before radiotherapy and were referred due to recurrent or progressive disease or
      intolerance to chemotherapy. All lesions were treated locally with a 2-3-cm
      safety margin with 4-6-MeV electron beams. Radiotherapy consisted of a single
      fraction of 8 Gy in the first four years and 6 Gy thereafter. RESULTS: The
      male:female ratio was 4:1. The median age was 61 years (range 18-87). Eight out
      of 47 patients (17%) had an underlying immunocompromised state, and one had a
      previous diagnosis of Hodgkin's disease. Of 203 fields treated, 51 and 152 fields
      were treated with 8 Gy and 6 Gy, respectively. Overall response rates (RR) at 12
      months for 8- and 6 Gy were 93% and 86%, which were not statistically different.
      However, the difference between complete RRs at 12 months (93% and 60% for 8 Gy
      and 6 Gy respectively) was significant (p<0.0001). Progression-free survival and
      reirradiation rates were not significantly different. Side effects were tolerable
      in all but three patients with grade 2-3 fibrosis and edema. CONCLUSION:
      Radiotherapy is an effective mode of treatment for Kaposi's sarcoma, and a single
      dose of 8 Gy is more effective in terms of complete RR compared to 6 Gy, though
      overall response and progression-free survival rates were similar.

PMID- 16895286
TI  - Relationship of African Americans' sociodemographic characteristics to belief in
      conspiracies about HIV/AIDS and birth control.
AB  - Although prior research shows that substantial proportions of African Americans
      hold conspiracy beliefs, little is known about the subgroups of African Americans
      most likely to endorse such beliefs. We examined the relationship of African
      Americans' sociodemographic characteristics to their conspiracy beliefs about
      HIV/AIDS and birth control. Anonymous telephone surveys were conducted with a
      targeted random-digit-dial sample of 500 African Americans (15-44 years) in the
      contiguous United States. Respondents reported agreement with statements
      capturing beliefs in HIV/AIDS conspiracies (one scale) and birth control
      conspiracies (two scales). Sociodemographic variables included gender, age,
      education, employment, income, number of people income supports, number of living
      children, marital/cohabitation status, religiosity and black identity.
      Multivariate analyses indicated that stronger HIV/AIDS conspiracy beliefs were
      significantly associated with male gender, black identity and lower income. Male
      gender and lower education were significantly related to black genocide
      conspiracy beliefs, and male gender and high religiosity were significantly
      related to contraceptive safety conspiracy beliefs. The set of sociodemographic
      characteristics explained a moderately small amount of the variance in conspiracy
      beliefs regarding HIV/AIDS (R2 range=0.07-0.12) and birth control (R2 range=0.05
      0.09). Findings suggest that conspiracy beliefs are not isolated to specific
      segments of the African-American population.

PMID- 16895287
TI  - Reducing African-American women's sexual risk: can churches play a role?
AB  - PURPOSE: This study investigates: 1) perceptions of clergy regarding their
      current counseling and the need for future programs concerning sexual risk
      taking, 2) sexual risk behaviors among a group of African-American women, 3)
      women's attitudes regarding condom use, and 4) women's receptiveness to church
      programs regarding sexual risks. METHODS: The clergy of 50 randomly selected
      predominantly African-American churches in five North Carolina counties were
      contacted regarding participation. Female parishioners ages 18-30 from
      participating churches were invited to complete written surveys concerning
      women's health. RESULTS: Of 50 clergy repeatedly contacted, 38 declined to
      participate and eight did not complete the interview. Only four interviews could
      be completed. Counseling regarding sexual risk was not common among the four
      clergy. They often advised parishioners to practice abstinence. Survey data was
      received from 142 respondents at 14 churches. Nearly 84% of the women surveyed
      had a history of sexually transmitted diseases (STDs). Almost all of the
      respondents were receptive to a church program regarding sexual risks.
      CONCLUSIONS: Despite the sexual risks among African-American women, in this
      study, many clergy were unwilling to address prevention and were uncomfortable
      discussing issues related to sexual health. However, the few clergy who agreed to
      participate were very receptive to future programs.

PMID- 16895288
TI  - What women want: understanding obesity and preferences for primary care weight
      reduction interventions among African-American and Caucasian women.
AB  - PURPOSE: To explore attitudes and perceptions of obesity, and identify
      preferences for weight-management interventions by African-American and Caucasian
      women who were followed in general internal medicine clinics. PROCEDURE: Surveys
      exploring these issues were mailed to African-American (n=240) and Caucasian
      (n=240) women with a BMI of > or =30. MAIN FINDINGS: Caucasian women felt past
      weight-loss efforts were helped by weight-loss programs significantly more than
      African-American women (P<0.001); African-American women were more likely to feel
      that their cultural background contributed to their weight gain than did
      Caucasian women (P=0.001). African-American women expressed a higher need for one
      on-one counseling with their physician (P<0.001) as well as group meetings with
      the dietician, physician and other women (P=0.004) than did Caucasian women.
      African-American women also felt it was more important for weight-loss programs
      to have information on food common to their culture than did Caucasian women
      (P<0.001). CONCLUSIONS: Differences in cultural background and preferences about
      weight loss interventions have important policy implications for how the U.S.
      healthcare system provides care to an ever-increasing multicultural population
      with a national epidemic such as obesity.

PMID- 16895289
TI  - Renal medullary carcinoma.
AB  - Renal medullary carcinoma is an epithelial malignant tumor arising from
      collecting duct epithelium. The tumor is almost exclusive to young black patients
      with the sickle cell hemoglobinopathies, mainly sickle cell trait (SCT). Most
      patients present with metastatic disease and have a worse prognosis. An African
      American male with sickle cell disease (HbSCD) who was diagnosed to have renal
      medullary carcinoma is presented here. The clinical, histologic and radiologic
      features of this tumor are described. In the setting of advanced disease,
      treatment modalities have proved largely unsuccessful. Given the shared
      demographic, clinical and radiographic features of these patients, awareness and
      early diagnosis may prove essential in improving survival.

PMID- 16895290
TI  - Tuberculous epididymitis presenting with Addison's disease: a rare case.
AB  - This report describes a case of tuberculosis with an atypical presentation
      characterized by epididymitis and Addison's disease in the absence of lung
      involvement. A 54-year-old male who presented with acute right scrotal pain and a
      whitish discharge, had been diagnosed four months earlier with acute epididymitis
      and prescribed ciprofloxacin. The clinical diagnosis was epididymitis and
      Addison's disease. Hydrocortisone therapy was initiated, and bilateral
      epididymectomy was undertaken. Biopsy specimen showed the presence of acid-fast
      bacilli and antituberculous treatment was initiated. On follow-up, the patient
      was in good clinical condition and free of symptoms. We conclude that tuberculous
      epididymitis can cause serious complications and should be included in the
      differential diagnosis for chronic epididymitis of unknown cause that does not
      respond to routine treatment. A high index of suspicion is required for
      diagnosis.

PMID- 16895292
TI  - Radiographic artifact mimicking epiphysis of the femoral head in a seven-month
      old girl.
AB  - Conventional x-ray is still the most important diagnostic and follow-up tool in
      developmental dysplasia of the hip joint, where hip joint ultrasonography cannot
      be performed. Artifacts that are seen because of technical errors can cause
      difficulties in diagnosis and and even can lead to wrong diagnoses and
      treatments. Herein, we report a diagnostic problem caused by an x-ray artifact in
      a child who is followed up with developmental dysplasia of the hip joint.

PMID- 16895291
TI  - Ulcer in the basis of Zenker's diverticulum mimicking esophageal malignancy.
AB  - Complications of Zenker's diverticulum are rare and include ulcer, bleeding and
      malignancy. Ulcer in the basis of diverticulum is a very rare complication and to
      date only four cases have been reported in the literature. Herein, we report a
      new case of ulcer in Zenker's diverticulum mimicking esophageal malignancy
      presumed to be due to aspirin and/or alcohol consumption. The exact diagnosis was
      troublesome and needed to perform diagnostic procedures repeatedly. The patient
      underwent external pharyngoesophageal diverticulectomy. We emphasize that
      endoscope should be withdrawn if any resistance is encountered during esophageal
      intubation-even with forward-viewing endoscope-especially when there is a
      Zenker's diverticulum suspicion and the patient receives ulcerogenic agents.
      Endoscopic examination should be performed prior to any definitive surgical
      procedure in all patients with Zenker's diverticulum.

PMID- 16895293
TI  - Case of fatal sickle cell intrahepatic cholestasis despite use of exchange
      transfusion in an African-American patient.
AB  - Sickle cell intrahepatic cholestasis (SCIC) is a rare complication of sickle cell
      anemia, characterized by marked hyperbilirubinemia and acute hepatic failure with
      an often fatal course. However, the few reported adult cases that were treated
      with exchange transfusion had a favorable outcome. We herein describe a 48-year
      old African-American man with hemoglobin S/B thalassemia and previously treated
      hepatitis C with compensated cirrhosis, who presented with a total bilirubin of
      59.7 mg/dL and direct bilirubin of 43.6 mg/dL in the absence of
      choledocholithiasis. Despite an exchange transfusion and aggressive packed red
      blood cell transfusions, which successfully decreased the hemoglobin S levels to
      <15%, he perished from progressive hepatic and renal failure. Autopsy
      demonstrated extensive intrahepatocellular and intracanalicular cholestasis in a
      background of cirrhosis. Our case suggests that poor prognostic factors for adult
      SCIC patients treated with exchange transfusion may include older age and
      underlying hepatic disease.

PMID- 16895294
TI  - The wheelchair thrombosis syndrome.
AB  - OBJECTIVE: To report a case of deep vein thrombosis (DVT) related to prolonged
      wheelchair use. CASE REPORT: A 48-year-old patient with spastic quadriplegia
      usually spent 10-12 hours daily in a wheelchair. He suddenly developed marked
      swelling of his right foot, leg and thigh. His plasma D-dimer level was 1,030
      (normal <500) ng/ml. A duplex ultrasound revealed common femoral vein thrombosis.
      He was hospitalized and anticoagulated; his extremity swelling decreased
      considerably by day 45. Hypercoagulability work-up disclosed previously
      subclinical mild elevation of serum cardiolipin immunoglobulin G
      (antiphospholipid syndrome). This patient will receive longterm anticoagulation.
      CONCLUSION: Prolonged sitting in wheelchair may cause DVT. To enhance public
      recognition of this avoidable risk, we propose the term "wheelchair thrombosis
      syndrome."

PMID- 16895295
TI  - Radiation port wart: a distinct cutaneous lesion after radiotherapy.
AB  - LABELED BACKGROUND: Radiotherapy may cause common cutaneous side effects such as
      acute and chronic radiodermatitis and also rare skin conditions. CASE REPORT: A
      42-year-old woman who received radiotherapy for invasive breast carcinoma
      developed multiple, scaly, rough papules and nodules restricted to treatment
      fields six months after completion of the treatment. A relapse of the breast
      cancer and/or seborrheic keratosis was ruled out by histological confirmation of
      verruca vulgaris. CONCLUSION: We report the first case of verruca vulgaris
      associated with radiation treatment. Radiotherapists and dermatologists should be
      aware of this possibility and be able to differentiate it from other skin lesions
      associated with irradiation.

PMID- 16895296
TI  - Facemask general anesthesia for minor and outpatient surgery: a dying art?
AB  - Facemask general anesthesia is suitable for many minor surgeries but has become
      unpopular partly because of the laryngeal mask airway. Appropriate facemask
      anesthesia is safe, effective and cheap, and associated with minimal
      complications. It also improves the airway management skills of the
      anesthesiologist. The art and teaching of facemask anesthesia should be
      encouraged.

PMID- 16895297
TI  - Our race is not the problem.

PMID- 16895298
TI  - Unintended healthcare consequences of hurricane Katrina.

PMID- 16895299
TI  - HBCU medical school graduates.

PMID- 16895300
TI  - Response to "The need for logical application-based extensions in sickle cell
      disease research findings to changing lives in the ethnic context".

PMID- 16895301
TI  - What a bush veto would mean for stem cells.

PMID- 16895302
TI  - Calling all healers.

PMID- 16895303
TI  - A very special wedding.

PMID- 16895304
TI  - Lung cancer and the sexes.

PMID- 16895305
TI  - Yes, it really is brain surgery.

PMID- 16895306
TI  - The failed experiment.

PMID- 16895307
TI  - A stochastic model to evaluate options for antenatal genetic screening.
AB  - Haemoglobinopathies are a group of genetic disorders which are particularly
      prevalent among certain risk groups such as ethnic groups. Antenatal screening of
      potential haemoglobinopathy carriers allows early diagnosis for affected fetuses,
      leading to therapeutic intervention or termination. However, it has drawbacks
      such as screening costs and possible miscarriage as a result of fetal testing.
      This paper describes a model that allows the outcomes of a screening programme to
      be estimated for different risk groups. The model has been implemented as a
      computer package that can be used to inform decisions made by health care
      planners.

PMID- 16895308
TI  - A new organ transplantation location-allocation policy: a case study of Italy.
AB  - In this paper, we propose a location model for the optimal organization of
      transplant system. Instead of simulation approach, which is typical when facing
      many health care applications, our approach is distinctively based on a
      mathematical programming formulation of the relevant problem. In particular, we
      focus on the critical role of time in transplantation process as well as on a
      spatial distribution of transplant centers. The allocation of transplantable
      organs across regions with the objective of attaining regional equity in health
      care, is the aim of this paper. Our model differs from previous modeling
      approaches in that it considers the nationwide reorganization of the transplant
      system, identifying system barriers that may impair equity and efficiency. The
      demolition of these barriers may leads on a reduction of waiting lists and of
      wasted organs. We provide the basic structure and the properties of the model,
      and validate it on a real case study. The experimental validation of the model
      demonstrates the effectiveness and robustness of our proposal.

PMID- 16895309
TI  - Optimal pooled testing.
AB  - This paper first characterizes three pooled testing techniques for generic
      testing conditions. It then applies these methods to demonstrate potential costs
      savings for universal HIV screening in the United Stated and Thailand. The
      success of these techniques in general is shown to be dependent on the prevalence
      as well as the disparity in prevalence between high and low risk groups. Further
      limitations on effectiveness include the potential impact of dilution on
      sensitivity. This and other limitations are addressed in the second section which
      focuses on applications of the techniques. Cost reductions are demonstrated to be
      feasible at prevalence of up to 30% and increasing dramatically at lower rates.
      Applying optimal pooled testing to universal HIV screening would result in an
      annual savings of over $1.4 billion in the United States and over $130 million in
      Thailand. Recent calls for universal HIV testing are based on the cost
      effectiveness of routine screening. These assessments may substantially overstate
      the cost of routine screening which strengthens the argument for universal
      screening.

PMID- 16895310
TI  - Perceptual structure of the desired functionality of internet-based health
      information systems.
AB  - With the emergence of the Internet, new health information systems are being
      designed and implemented that focus on coordination between providers, patients,
      payors and other constituents. While the importance of end user input in
      identifying the desired functionality of systems has long been recognized, very
      little work focuses on how users perceive the desired functionalities of these
      new systems to group together, and the implications of these groupings for the
      organization of functionalities into program modules and associated user
      interfaces. In this paper, we advance the construct, user based perceptual
      structure of desired functionality, in the context of these new coordination
      intensive health information systems. Perceptual structure depicts how users
      perceive different desired system functions to group together. A conceptual
      framework is advanced which links perceptual structure to two broad categories of
      components, external coordination and internal coordination, which are related to
      prospective beliefs about system value. The framework is tested empirically via
      two field studies conducted by a hospital chain focusing on two major user
      groups, physicians and office administrators. The setting involves a proposed
      Internet-based health information system that links various constituencies in the
      service delivery chain. The empirically generated perceptual structure is found
      to be largely supportive of its conceptual counterpart. Implications for the
      design and development of this new class of systems, and public policy
      implications of such new systems are presented.

PMID- 16895311
TI  - A biobjective model for the locational planning of hospitals and health centers.
AB  - The aim of this paper is to propose a new location-allocation structure, in an
      effort to improve the operational shortcomings of the existing locations of
      primary health care centers. These shortcomings are mainly caused by the
      preference of patients to use local hospitals rather than health centers. The
      method is based on a biobjective mathematical programming model for locating
      hospitals and primary health care centers. Two objectives are considered: (1)
      minimization of distance between patients and facilities, (2) equitable
      distribution of the facilities among citizens. We formulate the model taking into
      consideration the interdependence of the locations i.e., the general hospitals
      and health centers. This approach enables us to introduce a new aspect to the
      location problem, namely public preferences and also to consider the
      decentralization of the health care system. In order to represent the available
      information we employ Geographic Information Systems (GIS). We apply this model
      in the area of Western Greece and then compare our results with the solution
      originally selected by planners. Demographic data concerning the major and minor
      population centers of the area were based on the latest census of 2001. The
      results confirm the necessity of applied scientific approaches for regulating the
      health care system in order to establish rational strategic planning and ensure
      the best use of the available resources.

PMID- 16895312
TI  - Analysis of uncompensated hospital care using a DEA model of output congestion.
AB  - Uncompensated care can create financial difficulties for hospitals. The problem
      is likely to worsen as the number of individuals lacking health insurance
      continues to grow. The objective of this study is to measure how uncompensated
      care affects hospitals' ability to provide the services for which they do receive
      compensation. Applying output-based data envelopment analysis (DEA) under various
      assumptions on the disposability of outputs to a sample of Pennsylvania
      hospitals, we find that, on average, hospitals could have produced 7% more output
      if they had all operated on the best-practice frontier and that uncompensated
      care reduced the production of other hospital outputs by 2%. Thus, even if
      hospitals were to operate efficiently, they might still face financial distress
      as a result of providing uncompensated care. The findings in our study suggest
      that policy makers should continue looking at ways to increase funding to
      hospitals providing uncompensated care while not distorting economic incentives
      to reduce excessive costs.

PMID- 16895314
TI  - Jet-based methods to print living cells.
AB  - Cell printing has been popularized over the past few years as a revolutionary
      advance in tissue engineering has potentially enabled heterogeneous 3-D scaffolds
      to be built cell-by-cell. This review article summarizes the state-of-the-art
      cell printing techniques that utilize fluid jetting phenomena to deposit 2- and 3
      D patterns of living eukaryotic cells. There are four distinct categories of
      jetbased approaches to printing cells. Laser guidance direct write (LG DW) was
      the first reported technique to print viable cells by forming patterns of
      embryonic-chick spinal-cord cells on a glass slide (1999). Shortly after this,
      modified laser-induced forward transfer techniques (LIFT) and modified ink jet
      printers were also used to print viable cells, followed by the most recent
      demonstration using an electrohydrodynamic jetting (EHDJ) method. The low cost of
      some of these printing technologies has spurred debate as to whether they could
      be used on a large scale to manufacture tissue and possibly even whole organs.
      This review summarizes the published results of these cell printers (cell
      viability, retained genotype and phenotype), and also includes a physical
      description of the various jetting processes with a discussion of the stresses
      and forces that may be encountered by cells during printing. We conclude the
      review by comparing and contrasting the different jet-based techniques, while
      providing a map for future experiments that could lead to significant advances in
      the field of tissue engineering.

PMID- 16895313
TI  - A descriptive analysis of average productivity among health maintenance
      organizations, 1985 to 2001.
AB  - This paper examines the evolution of average productivity among HMOs for 4,419
      Health Maintenance Organizations (HMOs) from 1985 to 2001. For both IPA and non
      IPA HMOs, HMO productivity increased from 1990 to 1996 and rapidly decreased from
      1997 to 2001. In contrast to cost functions that show scale economies for IPA and
      non-IPA HMOs, production functions showed scale economies for IPA HMOs were
      constant and non-IPA HMOs having only slight scale economies. This suggests that
      much of the scale economies observed in cost functions are due to lower prices
      for resources used rather than improvements in production organization. Non-IPA
      HMOs and non-profit HMOs are more productive than IPA HMOs and for profit HMOs.
      Production organization for non-IPA HMOs appears to have improved over time,
      resulting in non-IPA HMOs being able to produce more member months of coverage
      with their production organization in 1997 to 2001 than they would have with
      their production organization in 1985 to 1990. Regulations requiring consumer
      involvement in HMO governance reduce productivity.

PMID- 16895316
TI  - Advances in time-resolved approaches to characterize the dynamical nature of
      enzymatic catalysis.

PMID- 16895317
TI  - Spectroscopic characterization of distortion in enzyme complexes.

PMID- 16895318
TI  - An NMR perspective on enzyme dynamics.

PMID- 16895319
TI  - Single molecule studies of enzyme mechanisms.

PMID- 16895320
TI  - Tunneling and dynamics in enzymatic hydride transfer.

PMID- 16895321
TI  - Computational approaches: reaction trajectories, structures, and atomic motions.
      Enzyme reactions and proficiency.

PMID- 16895323
TI  - Computational and theoretical methods to explore the relation between enzyme
      dynamics and catalysis.

PMID- 16895325
TI  - Electrostatic basis for enzyme catalysis.

PMID- 16895322
TI  - Multidimensional tunneling, recrossing, and the transmission coefficient for
      enzymatic reactions.

PMID- 16895326
TI  - Activation of oxygen nucleophiles in enzyme catalysis.

PMID- 16895327
TI  - Enzymatic mechanisms of phosphate and sulfate transfer.

PMID- 16895324
TI  - Mechanisms and free energies of enzymatic reactions.

PMID- 16895328
TI  - Mechanism-based profiling of enzyme families.

PMID- 16895330
TI  - Metals and their scaffolds to promote difficult enzymatic reactions.

PMID- 16895329
TI  - Free radical mechanisms in enzymology.

PMID- 16895331
TI  - The catalytic mechanisms of binuclear metallohydrolases.

PMID- 16895332
TI  - Nature's inventory of halogenation catalysts: oxidative strategies predominate.

PMID- 16895333
TI  - Degrees of difficulty of water-consuming reactions in the absence of enzymes.

PMID- 16895334
TI  - Breaking the central dogma by RNA editing.

PMID- 16895335
TI  - Structural biology and chemistry of the terpenoid cyclases.

PMID- 16895337
TI  - Assembly-line enzymology for polyketide and nonribosomal Peptide antibiotics:
      logic, machinery, and mechanisms.

PMID- 16895338
TI  - SiC nanotubes: A novel material for hydrogen storage.
AB  - A multiscale theoretical approach is used for the investigation of hydrogen
      storage in silicon-carbon nanotubes (SiCNTs). First, ab initio calculations at
      the density functional level of theory (DFT) showed an increase of 20% in the
      binding energy of H2 in SiCNTs compared with pure carbon nanotubes (CNTs). This
      is explained by the alternative charges that exist in the SiCNT walls. Second,
      classical Monte Carlo simulation of nanotube bundles showed an even larger
      increase of the storage capacity in SiCNTs, especially in low temperature and
      high-pressure conditions. Our results verify in both theoretical levels that
      SiCNTs seem to be more suitable materials for hydrogen storage than pure CNTs.

PMID- 16895336
TI  - Probing enzyme phosphoester interactions by combining mutagenesis and chemical
      modification of phosphate ester oxygens.

PMID- 16895340
TI  - Measurement of the thermal conductivity of individual carbon nanotubes by the
      four-point three-omega method.
AB  - The thermal conductivity of individual multiwalled carbon nanotubes was measured
      by utilizing the four-point-probe third-harmonic method, based on the fact that
      the third harmonic amplitude and phase as a response to applied alternate current
      at fundamental frequency, omega, can be expressed in terms of thermal
      conductivity and diffusivity. To this end, a microfabricated device composed of
      four metal electrodes was modified to manufacture nanometer-sized wires by using
      a focused ion beam source. A carbon nanotube could then be suspended over a deep
      trench milled by the focused ion beam, preventing heat loss to the substrate.
      Compared with the two-point-probe technique, a significant improvement in
      accuracy is assured by using four probes, because the contact contribution to the
      determination of the thermal conductivity is eliminated, making it possible to
      measure the correct signals of first and third harmonics. The multiwalled carbon
      nanotube was modeled as a one-dimensional diffusive energy transporter and its
      thermal conductivity was measured at room temperature under vacuum to be 300 +/-
      20 W/mK.

PMID- 16895339
TI  - Toward the nanoscopic "electronic nose": hydrogen vs carbon monoxide
      discrimination with an array of individual metal oxide nano- and mesowire
      sensors.
AB  - The array of chemiresistors made of individual pristine SnO2, surface doped (Ni)
      SnO2 nanowires, and TiO2 and In2O3 mesoscopic whiskers was fabricated on a
      Si/SiO2 wafer. Their conductance was measured under pulses of H2 and CO reducing
      gases in oxygen as background gas. The nanostructures were shown to be n-type
      semiconductors possessing high sensitivity to the target gases. Following the
      "electronic nose" concept, correlation analysis of response of three
      chemiresistor array is shown to be sufficient to discriminate between H2 and CO
      signals.

PMID- 16895341
TI  - Fabrication of coaxial metal nanocables using a self-assembled peptide nanotube
      scaffold.
AB  - The design and fabrication of complex nanostructures with specific geometry and
      composition is one of the main challenges of nanotechnology. Here we demonstrate
      the devise of metal-insulator-metal, trilayered, coaxial nanocables. Such coaxial
      geometry may give rise to useful and unique electromagnetic properties. We have
      fabricated these nanostructures using a scaffold of self-assembled peptide
      nanotubes. Gold nanoparticles were bound to the surface of peptide nanotubes via
      a common molecular recognition element that was included in various linker
      peptides. This enabled us to promote site-specific metal reduction and to create
      the coaxial nanostructure. Using electron microscopy, 1H NMR spectra, and energy
      dispersive X-ray analysis, we monitored the different steps within the process,
      gaining further understanding of its mechanism.

PMID- 16895343
TI  - Photoluminescence imaging of suspended single-walled carbon nanotubes.
AB  - Single-walled carbon nanotubes (SWNTs) suspended in air over trenches are imaged
      using their intrinsic near-infrared (NIR) photoluminescence (1.0-1.6 microm). Far
      field emission from extended suspended lengths (approximately 50 microm) is both
      spatially and spectrally resolved, and SWNTs are classified based on the spatial
      uniformity of their emission intensity and emission wavelength. In a few cases,
      emission assigned to different (n,m) species is observed along the same suspended
      segment. Most SWNTs imaged on millisecond time scales show steady emission, but a
      few fluctuate and suffer a reduction of intensity. The quantum efficiency is
      dramatically higher than that in previous reports and is estimated at 7%, a value
      that is precise but subject to corrections because of assumptions about
      absorption and coherence.

PMID- 16895342
TI  - Volatile organic compound detection using nanostructured copolymers.
AB  - Regioregular polythiophene-based conductive copolymers with highly crystalline
      nanostructures are shown to hold considerable promise as the active layer in
      volatile organic compound (VOC) chemresistor sensors. While the regioregular
      polythiophene polymer chain provides a charge conduction path, its chemical
      sensing selectivity and sensitivity can be altered either by incorporating a
      second polymer to form a block copolymer or by making a random copolymer of
      polythiophene with different alkyl side chains. The copolymers were exposed to a
      variety of VOC vapors, and the electrical conductivity of these copolymers
      increased or decreased depending upon the polymer composition and the specific
      analytes. Measurements were made at room temperature, and the responses were
      found to be fast and appeared to be completely reversible. Using various
      copolymers of polythiophene in a sensor array can provide much better
      discrimination to various analytes than existing solid state sensors. Our data
      strongly indicate that several sensing mechanisms are at play simultaneously, and
      we briefly discuss some of them.

PMID- 16895344
TI  - Biocompatibility and toxicological studies of carbon nanotubes doped with
      nitrogen.
AB  - In this report, we compare the toxicological effects between pure carbon
      multiwalled nanotubes (MWNTs) and N-doped multiwalled carbon (CNx) nanotubes.
      Different doses of tubes were administered in various ways to mice: nasal, oral,
      intratracheal, and intraperitoneal. We have found that when MWNTs were injected
      into the mice's trachea, the mice could die by dyspnea depending on the MWNTs
      doses. However, CNx nanotubes never caused the death of any mouse. We always
      found that CNx nanotubes were far more tolerated by the mice when compared to
      MWNTs. Extremely high concentrations of CNx nanotubes administrated directly into
      the mice's trachea only induced granulomatous inflammatory responses.
      Importantly, all other routes of administration did not induce signs of distress
      or tissue changes on any treated mouse. We therefore believe that CNx nanotubes
      are less harmful than MWNTs or SWNTs and might be more advantageous for
      bioapplications.

PMID- 16895345
TI  - Synthesis and properties of single-crystal FeSi nanowires.
AB  - We report for the first time the chemical synthesis of free-standing single
      crystal nanowires (NWs) of FeSi, the only transition-metal Kondo insulator and
      the host structure for ferromagnetic semiconductor Fe(x)Co(1-x)Si. Straight and
      smooth FeSi nanowires are produced on silicon substrates covered with a thin
      layer of silicon oxide through the decomposition of the single-source
      organometallic precursor trans-Fe(SiCl3)2(CO)4 in a simple chemical vapor
      deposition process. Unlike typical vapor-liquid-solid (VLS) NW growth, FeSi NWs
      form without the addition of metal catalysts, have no catalyst tips, and depend
      strongly on the surface employed. X-ray spectroscopy verifies the identity and
      the room-temperature metallic nature of FeSi NWs. Room-temperature electrical
      transport measurements using NW devices show an average resistivity of 210 micro
      Omega cm, similar to the value for bulk FeSi. Investigations into the low
      temperature physical properties of the first one-dimensional Kondo insulator and
      the possible new NW growth mechanism are underway. This unique synthetic approach
      to FeSi NWs will be generally applicable to many other transition-metal
      silicides.

PMID- 16895346
TI  - Nanoscale paul trapping of a single electron.
AB  - We demonstrate that a Paul trap made up of four conducting nanotubes is capable
      of trapping a single electron. In addition to the size, the major differences
      between such a nano-trap and its macroscopic analogue are that the electron is
      treated as a quantum object and that its effect ("back reaction") on the trapping
      device cannot be ignored. We computationally demonstrate focusing and trapping of
      an electronic wave packet, while fully accounting for the image charges induced
      by the electron on the nanotubes. The electron image charge interaction
      significantly affects the electron dynamics, and thus the trap stability. An
      (entangled) set of trapped electrons offers a number of advantages for quantum
      information processing.

PMID- 16895347
TI  - Radius and chirality dependent conformation of polymer molecule at nanotube
      interface.
AB  - Temperature-dependent conformations of linear polymer molecules adsorbed at
      carbon nanotube (CNT) interfaces are investigated through molecule dynamics
      simulations. Model polyethylene (PE) molecules are shown to have selective
      conformations on the CNT surface, controlled by atomic structures of the CNT
      lattice and geometric coiling energy. PE molecules form entropy driven assembly
      domains, and their preferred wrapping angles around large radius CNT (40, 40)
      reflect the molecule configurations with energy minimums on a graphite plane.
      While PE molecules prefer 0 degrees wrapping on small radius armchair CNT (5, 5)
      predominantly at low temperatures, their configurations are shifted to larger
      wrapping angle ones on a similar radius zigzag CNT (10, 0). A nematic
      transformation around 280 K is identified through the Landau-de Gennes theory,
      with molecule aligning along tube axis in extended conformations.

PMID- 16895348
TI  - Carbon nanotube DNA sensor and sensing mechanism.
AB  - We report the fabrication of single-walled carbon nanotube (SWNT) DNA sensors and
      the sensing mechanism. The simple and generic protocol for label-free detection
      of DNA hybridization is demonstrated with random sequence 15mer and 30mer
      oligonucleotides. DNA hybridization on gold electrodes, instead of on SWNT
      sidewalls, is mainly responsible for the acute electrical conductance change due
      to the modulation of energy level alignment between SWNT and gold contact. This
      work provides concrete experimental evidence on the effect of SWNT-DNA binding on
      DNA functionality, which will help to pave the way for future designing of SWNT
      biocomplexes for applications in biotechnology in general and also DNA-assisted
      nanotube manipulation techniques.

PMID- 16895349
TI  - TaSi2 nanowires: A potential field emitter and interconnect.
AB  - TaSi2 nanowires have been synthesized on a Si substrate by annealing NiSi2 films
      at 950 degrees C in an ambient containing Ta vapor. The nanowires could be grown
      up to 13 microm in length. Field-emission measurements show that the turn-on
      field is low at 4-4.5 V/microm and the threshold field is down to 6 V/microm with
      the field enhancement factor as high as 1800. The metallic TaSi2 nanowires
      exhibit excellent electrical properties with a remarkable high failure current
      density of 3 x 10(8) A cm(-2). In addition, effects of annealing temperatures and
      capability of metal silicide mediation layer on the growth of nanowires are
      addressed. This simple approach promises future applications in nanoelectronics
      and nano-optoelectronics.

PMID- 16895350
TI  - Na(Y1.5 Na0.5)F6 single-crystal nanorods as multicolor luminescent materials.
AB  - A facile wet chemical synthesis method was used to prepare a range of single
      crystal Na(Y1.5 Na0.5)F6 nanorods with controllable aspect ratios. Their novel
      multicolor upconversion (UC) fluorescence has been successfully realized by
      doping Yb3+/Er3+ (green) and Yb3+/Tm3+ (blue) ion pairs. When doped with Eu3+ and
      Tb3+ ions, the strong red and green downconversion (DC) fluorescence has also
      been observed, respectively. Being covered with oleic acids, these luminescent
      nanorods have been transparently dispersed in nonpolar solvent. For their unique
      luminescence and controllable morphology and surface properties, these nanorods
      may find great applications in the fields of color displays, biolabels, light
      emitting diodes (LEDs), optical storage, optoelectronics, anticounterfeiting, and
      solid-state lasers.

PMID- 16895351
TI  - Periodically twinned nanowires and polytypic nanobelts of ZnS: The role of mass
      diffusion in vapor-liquid-solid growth.
AB  - There are two mass diffusion processes regarding the vapor-liquid-solid (VLS)
      growth of nanostructures: one is inside the catalyst droplet toward the liquid
      solid interface; the other is along the side surface planes of the growing
      nanostructures. In this letter, microscale, modulated mass diffusion scenarios
      are exhibited through the synthesis of two types of ZnS nanostructures in an Au
      catalyzed VLS process: periodically twinned nanowires originated from periodical
      fluctuation between diffusion rate inside the catalytic droplet and the growth
      rate on the liquid-solid interface; the formation of asymmetrically polytypic
      nanobelts is related to one certain side surface bounded by high surface-energy
      plane, which serves as a preferential diffusion direction of reactant adatoms.
      The results may have important impact on the understanding of the physical and
      chemical process of the VLS mechanism. These longitudinally and latitudinally
      tunable crystalline structures enrich the family of one-dimensional nano-building
      blocks, and may find potential applications in nanotechnology.

PMID- 16895352
TI  - Piezoelectric and semiconducting coupled power generating process of a single ZnO
      belt/wire. A technology for harvesting electricity from the environment.
AB  - This paper presents the experimental observation of piezoelectric generation from
      a single ZnO wire/belt for illustrating a fundamental process of converting
      mechanical energy into electricity at nanoscale. By deflecting a wire/belt using
      a conductive atomic force microscope tip in contact mode, the energy is first
      created by the deflection force and stored by piezoelectric potential, and later
      converts into piezoelectric energy. The mechanism of the generator is a result of
      coupled semiconducting and piezoelectric properties of ZnO. A piezoelectric
      effect is required to create electric potential of ionic charges from elastic
      deformation; semiconducting property is necessary to separate and maintain the
      charges and then release the potential via the rectifying behavior of the
      Schottky barrier at the metal-ZnO interface, which serves as a switch in the
      entire process. The good conductivity of ZnO is rather unique because it makes
      the current flow possible. This paper demonstrates a principle for harvesting
      energy from the environment. The technology has the potential of converting
      mechanical movement energy (such as body movement, muscle stretching, blood
      pressure), vibration energy (such as acoustic/ultrasonic wave), and hydraulic
      energy (such as flow of body fluid, blood flow, contraction of blood vessels)
      into electric energy that may be sufficient for self-powering nanodevices and
      nanosystems in applications such as in situ, real-time, and implantable
      biosensing, biomedical monitoring, and biodetection.

PMID- 16895353
TI  - Transmission electron microscopy study of individual carbon nanotube breakdown
      caused by Joule heating in air.
AB  - We present repeated structural and electrical measurements on individual
      multiwalled carbon nanotubes, alternating between electrical measurements under
      ambient conditions and transmission electron microscopy (TEM). The multiwalled
      carbon nanotubes made by chemical vapor deposition were manipulated onto
      cantilever electrodes extending from a specially designed microfabricated chip.
      Repeated TEM investigations were then made of the progressive destruction of the
      nanotube structure induced by Joule heating in air. The electrical measurements
      indicate that the studied nanotubes behave as diffusive conductors with
      remarkably predictable electrical properties despite extensive structural damage.

PMID- 16895354
TI  - Amplitude response of single-wall carbon nanotube probes during tapping mode
      atomic force microscopy: Modeling and experiment.
AB  - Imaging of surfaces with carbon nanotube probes in tapping mode results
      frequently in complex behavior in the amplitude-distance curves monitored. Using
      molecular mechanics simulations, we calculate the force exerted on a nanotube
      pressed against a smooth surface as it undergoes deformation and buckling. This
      nonlinear force is then used in a macroscopic equation, describing the response
      of a damped harmonic oscillator, to predict the amplitude response of a nanotube
      AFM probe. Similarities between the prediction and experiment suggest that the
      complex amplitude response seen in the experiment may be explained by the
      nonlinearity in the force exerted on the nanotube and thus must not necessarily
      be related to the structure of the surface.

PMID- 16895355
TI  - Influence of polymer-blend morphology on charge transport and photocurrent
      generation in donor-acceptor polymer blends.
AB  - Monte Carlo algorithms are used to simulate the morphologies adopted by polymer
      chains in a polymer-blend film in the limits where the chains are mutually
      attractive (homophilic regime) and mutually repulsive (heterophilic regime) and
      then to simulate the drift transport of charges through the polymer chains. In
      the homophilic regime, chains aggregate into tangled domains resulting in a
      relatively high percolation threshold, a high density of configurational trap
      states, and slow, dispersive charge transport. In the heterophilic regime at the
      same polymer volume fraction, chains self-organize into a lacework pattern
      resulting in a low percolation threshold and efficient, trap-free charge
      transport. For homophilic morphologies interchain hopping is rate-limiting and
      mobility is insensitive to chain length, whereas for heterophilic morphologies
      intrachain transport is important and mobility increases with increasing chain
      length. The morphologies are used in simulations of photocurrent quantum
      efficiency for donor-acceptor blend photodiodes, which show that the effects of
      morphology on charge pair generation and recombination compete with the effect on
      transport, such that the optimum blend composition is sensitive to both
      morphology and recombination rate. We conclude that it is essential to consider
      the connectivity of and morphology adopted by polymer chains in the optimization
      of materials for organic solar cells.

PMID- 16895356
TI  - The importance of an endotoxin-free environment during the production of
      nanoparticles used in medical applications.
AB  - We investigated the effect of spherical gold nanoparticles on immature dendritic
      cells (DCs). Conventionally produced nanoparticles had a maturating effect on the
      DCs--a result of lipopolysaccharide (LPS) contamination. By modification of the
      production process, low-LPS particles were obtained, which had practically no
      effect on phenotypic maturation or cytokine production of the DCs. Our findings
      emphasize the importance of high purity in the production of nanoparticles, since
      possible contaminants may interfere with the assessment of biological/medical
      effects. They also highlight that nanoparticles can function as carriers of
      immune modulating contaminants.

PMID- 16895357
TI  - All-optical nanoscale pH meter.
AB  - We show that an Au nanoshell with a pH-sensitive molecular adsorbate functions as
      a standalone, all-optical nanoscale pH meter that monitors its local environment
      through the pH-dependent surface-enhanced Raman scattering (SERS) spectra of the
      adsorbate molecules. Moreover, we also show how the performance of such a
      functional nanodevice can be assessed quantitatively. The complex spectral output
      is reduced to a simple device characteristic by application of a locally linear
      manifold approximation algorithm. The average accuracy of the nano-"meter" was
      found to be +/-0.10 pH units across its operating range.

PMID- 16895358
TI  - Probing molecule-metal bonding in molecular junctions by inelastic electron
      tunneling spectroscopy.
AB  - We present first-principles calculations for the inelastic electron tunneling
      spectra (IETS) of three molecules, 1-undecane thiol (C11), alpha,omega
      bis(thioacetyl)oligophenylenethynylene (OPE), and alpha,omega
      bis(thioacetyl)oligophenylenevinylene (OPV), sandwiched between two gold
      electrodes. We have demonstrated that IETS is very sensitive to the bonding
      between the molecule and electrodes. In comparison with experiment of Kushmerick
      et al. (Nano Lett. 2004, 4, 639), it has been concluded that the C11 forms a
      strong chemical bond, while the bonding of the OPE and OPV systems are slightly
      weaker. All experimental spectral features have been correctly assigned.

PMID- 16895360
TI  - Orthogonal self-assembly of carbon nanotube crossbar architectures by
      simultaneous graphoepitaxy and field-directed growth.
AB  - Crossbar arrays of single-wall carbon nanotubes are produced spontaneously in a
      single step of chemical vapor deposition by simultaneous graphoepitaxy along
      faceted nanosteps and field-directed growth, perpendicular to each other. The two
      alignment mechanisms take place selectively on miscut C-plane sapphire and
      patterned amorphous SiO2 islands, respectively, without mutual interference,
      producing dense nanotube grids, with up to 12 junctions per square micrometer.
      This one-step method of orthogonal self-assembly may open up new possibilities
      for nanotube circuit integration.

PMID- 16895359
TI  - Real-time observation of tubule formation from amorphous carbon nanowires under
      high-bias Joule heating.
AB  - The tubule formation process from amorphous carbon nanowires under high-bias
      caused Joule heating was observed in real time in a high-resolution transmission
      electron microscope. The crystallization of the amorphous carbon nanowires
      occurred in two distinct ways: the formation of tubular graphitic basal planes
      parallel to the nanowire axis on the surface and the formation of nano-onions in
      the interior of the nanowire. The tubule formation mechanism is a process of
      solid-state atom diffusion at high temperatures. Energetically, the tubule
      formation is caused by the exceptionally low surface energy of the (0002) plane
      of graphite. Higher input power to the amorphous nanowires generally leads to
      improved graphitization and, in turn, to increased conductance. The results
      suggest that nanotube formation in the arc-discharge growth process may involve
      the formation and crystallization of amorphous carbon.

PMID- 16895361
TI  - Probing the electronic properties of self-organized poly(3-dodecylthiophene)
      monolayers by two-dimensional scanning tunneling spectroscopy imaging at the
      single chain scale.
AB  - Regioregular poly(3-dodecylthiophene) films self-organized on highly oriented
      pyrolytic graphite have been investigated by scanning tunneling microscopy and
      two-dimensional scanning tunneling spectroscopy (STS). Simulated spectra in very
      good agreement with the experimental data have been obtained by a method
      combining ab initio and semiempirical approaches, which allows a careful
      discussion of the polymer electronic states. From the experimental data, with the
      support of modeling, it is shown that the STS spectra give a direct access to the
      polymer semiconducting band gap without noticeable charge-transfer effects from
      the substrate. Spectroscopic images are achieved at the single chain scale, which
      allows scrutinizing the electronic consequences of chain folds and pi-stacking
      effects through spectroscopic contrasts. While chain folds do not locally
      increase the polymer band gap more than a few tens of millielectonvolt, a
      striking widening of the STS conductance gap is observed in the case of
      electronic tunneling through two interacting polymer layers. Scenarios based on
      nonplanar configuration of thiophene cycles within the second layer or variations
      of the charge screening effects are proposed to explain this phenomenon.

PMID- 16895362
TI  - Broadband ZnO single-nanowire light-emitting diode.
AB  - We present a novel technique for reliable electrical injection into single
      semiconductor nanowires for light-emitting diodes and lasers. The method makes
      use of a high-resolution negative electron-beam resist and direct electron-beam
      patterning for the precise fabrication of a metallic top contact along the length
      of the nanowire, while a planar substrate is used as a bottom contact. It can be
      applied to any nanowire structure with an arbitrary cross section. We demonstrate
      this technique by constructing the first zinc oxide single-nanowire light
      emitting diode. The device exhibits broad sub-bandgap emission at room
      temperature.

PMID- 16895363
TI  - Real-time shape evolution of nanoimprinted polymer structures during thermal
      annealing.
AB  - The real-time shape evolution of nanoimprinted polymer patterns is measured as a
      function of annealing time and temperature using critical dimension small-angle X
      ray scattering (CD-SAXS). Periodicity, line width, line height, and sidewall
      angle are reported with nanometer resolution for parallel line/space patterns in
      poly(methyl methacrylate) (PMMA) both below and above the bulk glass transition
      temperature (T(G)). Heating these patterns below T(G) does not produce
      significant thermal expansion, at least to within the resolution of the
      measurement. However, above T(G) the fast rate of loss in pattern size at early
      times transitions to a reduced rate in longer time regimes. The time-dependent
      rate of polymer flow from the pattern into the underlying layer, termed pattern
      "melting", is consistent with a model of elastic recovery from stresses induced
      by the molding process.

PMID- 16895364
TI  - Calcium-induced voltage gating in single conical nanopores.
AB  - We examine time signals of ion current through single conically shaped nanopores
      in the presence of sub-millimolar concentrations of calcium ions. We show that
      calcium induces voltage-dependent ion current fluctuations in time in addition to
      the previously reported negative incremental resistance (Nano Lett. 2006, 6, 473
      477). These current fluctuations occur on the millisecond time scale at voltages
      at which the effect of negative incremental resistance was observed. We explain
      the fluctuations as results of transient binding of calcium ions to carboxyl
      groups on the pore walls that cause transient changes in electric potential
      inside a conical nanopore. We support this explanation by recordings of ion
      current in the presence of manganese ions that bind to carboxyl groups 3 orders
      of magnitude more tightly than calcium ions. The system of a single conical
      nanopore with calcium ions is compared to a semiconductor device of a unijunction
      transistor in electronic circuits. A unijunction transistor also exhibits
      negative incremental resistance and current instabilities.

PMID- 16895365
TI  - Diffusion-limited patterning of molecules in nanofluidic channels.
AB  - Diffusion-limited patterning (DLP) is a new technique that enables patterning of
      labile molecular species in solution phase onto surfaces that are not easily
      accessible. This technique is self-aligning and is simple to implement for
      patterning multiple species. We demonstrated DLP by patterning alternating bands
      of fluorescently labeled and unlabeled streptavidin in biotin-functionalized
      nanofluidic channels with spatial resolution better than 1 microm. The
      methodology of DLP also enables experimental measurement of a unique parameter
      that relates molecular surface grafting density, concentration, diffusivity, and
      channel geometry.

PMID- 16895366
TI  - Facile one-pot synthesis of brush polymers through tandem catalysis using Grubbs'
      catalyst for both ring-opening metathesis and atom transfer radical
      polymerizations.
AB  - Using Grubbs' catalyst Cl2(PCy3)2Ru=CHPh for tandem catalysis, poly(methyl
      methacrylate)-based brush polymers were prepared by one-pot sequential ring
      opening metathesis polymerization (ROMP) and atom transfer radical polymerization
      (ATRP) via an inimer having both an alpha-bromoisobutyrate ATRP initiator
      functionality and an exo-norbornenyl ROMP monomer functionality. The surface
      morphologies and aggregation behaviors of these nanoscopic single molecules were
      studied by tapping-mode atomic force microscopy measurements on mica.

PMID- 16895367
TI  - Role of defects in single-walled carbon nanotube chemical sensors.
AB  - We explore the electronic response of single-walled carbon nanotubes (SWNT) to
      trace levels of chemical vapors. We find adsorption at defect sites produces a
      large electronic response that dominates the SWNT capacitance and conductance
      sensitivity. This large response results from increased adsorbate binding energy
      and charge transfer at defect sites. Finally, we demonstrate controlled
      introduction of oxidation defects can be used to enhance sensitivity of a SWNT
      network sensor to a variety of chemical vapors.

PMID- 16895368
TI  - Contact formation dynamics: Mapping chemical bond formation between a molecule
      and a metallic probe.
AB  - We present a study that maps out chemical bond formation between a Pt-inked probe
      and a single 1,3-cyclohexadiene (1,3-CHD) molecule on Si(100). By separating the
      mechanical and electronic contributions to the current during the approach to
      contact, we show that there are significant forces between the probe and the C=C
      of the molecule and we track the relaxation of the molecule, the emergence of a
      chemical bond feature in the LDOS, and the quenching of specific molecular
      vibrations during bond formation.

PMID- 16895369
TI  - Transient grating measurements of excitonic dynamics in single-walled carbon
      nanotubes: The dark excitonic bottleneck.
AB  - Transient grating measurements affirm the excitonic model for single-walled
      carbon nanotubes (SWNT) by identifying the dark exciton (D) as the population
      relaxation bottleneck in semiconducting-SWNT (S-SWNT). The data allow the
      reconstruction of the kinetics of excitonic cascade and cooling, from band
      continuum to vibrational cooling in the ground electronic state. In S-SWNT, the
      intraband relaxation occurs in 40 fs, localization into the 2g exciton occurs in
      50 fs, followed by the excitonic cascade: 2g --> 1u --> D --> 1g with time
      constants of 175 fs, 3 ps, 300 ps, respectively. Fluorescence from the 1u state
      is quenched by efficient population transfer to 1D dark exciton. In metallic
      tubes, cooling is completed on the time scale of 1 ps.

PMID- 16895370
TI  - Monolayered organosilicate toroids and related structures: A phase diagram for
      templating from block copolymers.
AB  - Here we report the controlled generation of micelle-templated organosilicate
      nanostructures resulting from self-assembly of a block copolymer/organosilicate
      mixture followed by organosilicate vitrification and copolymer thermolysis.
      Variation of solution condition and the copolymer/organosilicate mixture
      composition generates widely different film morphologies ranging from toroids to
      linear features to contiguous nanoporous monolayers. The use of reactive
      organosilicates for block copolymer templation generates functional inorganic
      nanostructures with thermal and mechanical stability.

PMID- 16895371
TI  - Nanocrystal shape and the mechanism of exciton spin relaxation.
AB  - The rate of exciton spin relaxation (flips) between the bright exciton states (F
      = +/-1) of CdSe nanocrystals is reported as a function of shape, for dots and
      nanorods. The spin relaxation is measured using an ultrafast transient grating
      method with a crossed linearly polarization sequence. It is found that the spin
      relaxation rate depends on the radius, not length, of the nanocrystals. That
      observation is explained by deriving an expression for the electronic coupling
      matrix element that mixes the bright exciton states.

PMID- 16895372
TI  - Overlayers on silver nanotriangles: Field confinement and spectral position of
      localized surface plasmon resonances.
AB  - We studied the spectral evolution of plasmon modes associated with silver
      nanotriangles as a function of dielectric overlayer thickness in the range of 5
      300 nm. A substantial red-shift of the resonance is observed that oscillates with
      increasing over-layer thickness. We explain this previously unreported
      oscillation through the cavity quantum electrodynamical effect of the array of
      triangles combined with the dielectric overlayer. The red-shift, though
      substantial, is less than expected. Comparison with numerical models indicates
      that this discrepancy is due to very tight field confinement around the tips of
      the triangles.

PMID- 16895373
TI  - Direct observation of six-membered rings in the upper and lower walls of a single
      wall carbon nanotube by spherical aberration-corrected HRTEM.
AB  - Atomic arrangements of the continuous network of six-membered rings in a single
      graphene sheet constituting a single-wall carbon nanotube was imaged successfully
      by employing a spherical aberration-corrected HRTEM operated at 120 kV
      acceleration voltage. Utilizing two advantages of the aberration-corrected HRTEM,
      the images separately resolved the rings in the upper and lower walls. Such
      images can be considered to be the first "tomographic" atomic images taken by
      HRTEM. This is a striking result that changes the conventional concept of HRTEM
      as a projection image.

PMID- 16895374
TI  - Molecular transport junctions: Propensity rules for inelastic electron tunneling
      spectra.
AB  - We develop a series of propensity rules for interpreting inelastic electron
      tunneling (IET) spectra of single-molecule transport junctions. IETS has no
      selection rules, such as those seen in optical, infrared, and Raman spectra,
      because IETS features arise not from the field-dipole interaction characterizing
      these other spectroscopies but from vibronic modification of the electronic
      levels. Expansion of the Landauer-Imry formula in Taylor series in molecular
      normal coordinates gives a convenient, accurate perturbation-type formula for
      calculating both frequency and intensity of the IETS spectrum. Expansion in a
      Dyson-like form permits derivation of propensity rules, both symmetry-based and
      pathway-deduced, allowing correlation of structure and coupling geometry with the
      IETS spectrum. These propensity rules work very well for the calculated spectrum
      of five typical molecular bridges.

PMID- 16895375
TI  - Photoinduced charge transfer and efficient solar energy conversion in a blend of
      a red polyfluorene copolymer with CdSe nanoparticles.
AB  - We present measurements of charge transfer and the photovoltaic effect in a blend
      of the alternating polyfluorene copolymer poly(2,7-(9,9-dioctyl-fluorene)-alt-5,5
      (4',7'-di-2-thienyl-2',1',3'-benzothiadiazole)) with branched CdSe nanoparticles.
      Quasi-steady-state photoinduced absorption measurements identified a long-lived
      charged species that formed after photoexcitation at room temperature.
      Photovoltaic devices based on this blend system showed a spectral response
      extending to 650 nm and gave a solar power conversion efficiency of 2.4% under
      Air Mass 1.5 Global (AM1.5G) conditions.

PMID- 16895376
TI  - Comparison of the abilities of ambient and manufactured nanoparticles to induce
      cellular toxicity according to an oxidative stress paradigm.
AB  - Nanomaterial properties differ from those bulk materials of the same composition,
      allowing them to execute novel activities. A possible downside of these
      capabilities is harmful interactions with biological systems, with the potential
      to generate toxicity. An approach to assess the safety of nanomaterials is
      urgently required. We compared the cellular effects of ambient ultrafine
      particles with manufactured titanium dioxide (TiO2), carbon black, fullerol, and
      polystyrene (PS) nanoparticles (NPs). The study was conducted in a phagocytic
      cell line (RAW 264.7) that is representative of a lung target for NPs.
      Physicochemical characterization of the NPs showed a dramatic change in their
      state of aggregation, dispersibility, and charge during transfer from a buffered
      aqueous solution to cell culture medium. Particles differed with respect to
      cellular uptake, subcellular localization, and ability to catalyze the production
      of reactive oxygen species (ROS) under biotic and abiotic conditions. Spontaneous
      ROS production was compared by using an ROS quencher (furfuryl alcohol) as well
      as an NADPH peroxidase bioelectrode platform. Among the particles tested, ambient
      ultrafine particles (UFPs) and cationic PS nanospheres were capable of inducing
      cellular ROS production, GSH depletion, and toxic oxidative stress. This toxicity
      involves mitochondrial injury through increased calcium uptake and structural
      organellar damage. Although active under abiotic conditions, TiO2 and fullerol
      did not induce toxic oxidative stress. While increased TNF-alpha production could
      be seen to accompany UFP-induced oxidant injury, cationic PS nanospheres induced
      mitochondrial damage and cell death without inflammation. In summary, we
      demonstrate that ROS generation and oxidative stress are a valid test paradigm to
      compare NP toxicity. Although not all materials have electronic configurations or
      surface properties to allow spontaneous ROS generation, particle interactions
      with cellular components are capable of generating oxidative stress.

PMID- 16895377
TI  - The controlled growth of GaN nanowires.
AB  - This paper reports a scalable process for the growth of high-quality GaN
      nanowires and uniform nanowire arrays in which the position and diameter of each
      nanowire is precisely controlled. The approach is based on conventional
      metalorganic chemical vapor deposition using regular precursors and requires no
      additional metal catalyst. The location, orientation, and diameter of each GaN
      nanowire are controlled using a thin, selective growth mask that is patterned by
      interferometric lithography. It was found that use of a pulsed MOCVD process
      allowed the nanowire diameter to remain constant after the nanowires had emerged
      from the selective growth mask. Vertical GaN nanowire growth rates in excess of 2
      mum/h were measured, while remarkably the diameter of each nanowire remained
      constant over the entire (micrometer) length of the nanowires. The paper reports
      transmission electron microscopy and photoluminescence data.

PMID- 16895378
TI  - Raman spectroscopy of single-wall boron nitride nanotubes.
AB  - Single-wall boron nitride nanotubes samples synthesized by laser vaporization of
      a hexagonal BN target under a nitrogen atmosphere are studied by UV and visible
      Raman spectroscopy. We show that resonant conditions are necessary for
      investigating phonon modes of BNNTs. Raman excitation in the UV (229 nm) provides
      preresonant conditions, allowing the identification of the A1 tangential mode at
      1370 cm(-1). This is 5 cm(-1) higher than the E(2g) mode in bulk h-BN. Ab initio
      calculations show that the lower frequency of bulk h-BN with respect to large
      diameter nanotubes and the single sheet of h-BN is related to a softening of the
      sp2 bonds in the bulk due to interlayer interaction.

PMID- 16895380
TI  - Observation of plasmon propagation, redirection, and fan-out in silver nanowires.
AB  - We report the coupling of free-space photons (vacuum wavelength of 830 nm) to
      surface plasmon modes of a silver nanowire. The launch of propagating plasmons,
      and the subsequent emission of photons, is selective and occurs only at ends and
      other discontinuities of the nanowire. In addition, we observe that the nanowires
      redirect the plasmons through turns of radii as small as 4 microm. We exploit the
      radiating nature of discontinuities to find a plasmon propagation length >3 +/- 1
      microm. Finally, we observe that interwire plasmon coupling occurs for
      overlapping wires, demonstrating plasmon fan-out at subwavelength scales.

PMID- 16895379
TI  - Au-free epitaxial growth of InAs nanowires.
AB  - III-V nanowires have been fabricated by metal-organic vapor-phase epitaxy without
      using Au or other metal particles as a catalyst. Instead, prior to growth, a thin
      SiOx layer is deposited on the substrates. Wires form on various III-V substrates
      as well as on Si. They are nontapered in thickness and exhibit a hexagonal cross
      section. From high-resolution X-ray diffraction, the epitaxial relation between
      wires and substrates is demonstrated and their crystal structure is determined.

PMID- 16895381
TI  - Thermal conductivity of diamond nanorods: Molecular simulation and scaling
      relations.
AB  - Thermal conductivities of diamond nanorods are estimated from molecular
      simulations as a function of radius, length, and degree of surface
      functionalization. While thermal conductivity is predicted to be lower than
      carbon nanotubes, their thermal properties are less influenced by surface
      functionalization, making them prime candidates for thermal management where heat
      transfer is facilitated by cross-links. A scaling relation based on phonon
      surface scattering is developed that reproduces the simulation results and
      experimental measurements on silicon nanowires.

PMID- 16895382
TI  - Self-assembled stripe patterns of CdS nanorods.
AB  - Sterically stabilized CdS nanorods, 3-5 nm in diameter with aspect ratios ranging
      from 4 to 15, were observed to self-align into networks of stripes several
      micrometers long when drop-cast from dispersions at submonolayer coverage. The
      stripes are two to three nanorods thick with nanorods assembled side-by-side with
      their long axes parallel to the stripe direction. Energetic forces between
      nanorods, such as van der Waals and dipole-dipole attractions, favor parallel
      nanorod alignment; however, we propose that pattern formation is kinetically
      limited, or mediated, by solvent evaporation.

PMID- 16895383
TI  - Pressure-induced infiltration of aqueous solutions of multiple promoters in a
      nanoporous silica.
AB  - By applying an external pressure, an aqueous solution of promoters can be forced
      into a hydrophobic nanoporous silica gel. The promoter molecule demands a free
      volume several times larger than itself to enter the nanoenvironment. The free
      volume size is a function of the promoter concentration. If more than one
      promoter is used, the system behavior does not follow the principle of
      superposition. These results have important relevance to intelligent absorption
      and adsorption, programmable catalysis, and so on.

PMID- 16895384
TI  - Superoxo, peroxo, and hydroperoxo complexes formed from reactions of rhodium
      porphyrins with dioxygen: thermodynamics and kinetics.
AB  - Rhodium(II) porphyrin complexes react with dioxygen to form terminal superoxo and
      bridged mu-peroxo complexes. Equilibrium constants for dioxygen complex formation
      with rhodium(II) tetramesitylporphyrin ((TMP)Rh*) and a m-xylyl-tethered
      dirhodium(II) diporphyrin complex (*Rh(m-xylyl)Rh*) are reported. (TMP)Rh-H
      reacts with oxygen to form a transient hydroperoxy complex ((TMP)Rh-OOH), which
      reacts on to form the rhodium(II) complex ((TMP)Rh*) and water. Kinetic studies
      for reactions of (TMP)Rh-H with O2 suggest a near concerted addition of dioxygen
      to the (TMP)Rh-H unit. Reactivity studies for mixtures of H2/O2 and CH4/O2 with
      the dirhodium(II) complex (*Rh(m-xylyl)Rh*) are reported.

PMID- 16895385
TI  - Au(I)-catalyzed annulation of enantioenriched allenes in the enantioselective
      total synthesis of (-)-rhazinilam.
AB  - Highly stereoselective Au(I)-catalyzed pyrrole additions to enantioenriched
      allenes afford a unique entry to optically active heterocycles. Asymmetric
      quaternary carbons can be installed with concurrent heterocycle annulation
      utilizing this methodology. The enantioenriched allenes are conveniently obtained
      by catalytic asymmetric acyl halide-aldehyde cyclocondensations and SN2' ring
      opening of the resulting enantioenriched beta-lactones. An enantioselective total
      synthesis of (-)-rhazinilam highlights the potential utility of this reaction
      technology in target-oriented synthesis.

PMID- 16895386
TI  - Enantioselective organocatalytic tandem Michael-Aldol reactions: one-pot
      synthesis of chiral thiochromenes.
AB  - A highly enantioselective (S) diphenylpyrrolinol silyl ether promoted tandem
      Michael-aldol reaction of alpha,beta-unsaturated aldehydes with 2
      mercaptobenzaldehydes has been developed. The method affords one-pot access to
      chiral and synthetically useful thiochromenes in high yields and high
      enantioselectivities from readily available compounds.

PMID- 16895388
TI  - Vanadium-catalyzed addition of propargyl alcohols and imines.
AB  - A Mannich-type addition of propargylic alcohols and N-methoxycarbonylimines has
      been achieved by using a vanadium catalyst. The reactivity of the vanadium
      catalyst could be modulated by modifying the silanol ligands to avoid the
      background reaction. The strategy described herein provides an atom-economical
      access to beta-aryl-substituted Z-enones with an allylic amino functional group,
      which are not readily accessible with other methods.

PMID- 16895389
TI  - Enantioselective carbolithiation initiated cascade reactions.
AB  - Enantioselective cascade reactions are very powerful synthetic protocols for the
      assembly of complex architectures. Our current approach is to exploit a (-)
      sparteine-controlled enantioselective carbolithiation of 2-propenylarylamines to
      provide chiral intermediates, which depending upon choice of electrophile are
      subsequently in situ converted into products of increasing complexity. The chiral
      center, formed in high enantiomeric ratio in the first carbolithiation step, is
      carried through the cascade reaction sequence to the final products and is
      independent of electrophile used. The scope of the cascade reaction is outlined
      in terms of reaction conditions, alkyllithiums, and electrophiles.

PMID- 16895387
TI  - Elucidating the effect of additives on the growth and stability of Cu2O surfaces
      via shape transformation of pre-grown crystals.
AB  - A new strategy of using pre-grown crystals to study preferential adsorption of
      various additives is demonstrated for the electrocrystallization of Cu2O. In this
      method, micron-size Cu2O crystals with well-defined cubic and octahedral shapes
      were first electrochemically grown, and their crystallization was resumed in a
      medium containing the additive to be investigated (e.g., Na+, NH4+, SO42-, Cl-,
      dodecyl sulfate). This method makes it possible to systematically study the
      interaction of additives with specific planes (e.g., {100} of a cube and {111} of
      an octahedron) already present. By observing shape transformation over time, the
      relative stabilities of {100}, {111}, and {110} planes of Cu2O in various growth
      media could be determined. During this study, a general scheme of forming new
      crystal shapes containing crystallographic planes that cannot be directly
      stabilized by preferential adsorption alone was also established (i.e.,
      rhombicuboctahedral shape of Cu2O containing {110} planes). This method can be
      extended to other crystal systems, which will enable us to classify common
      features of additives (e.g., charges, type of atoms) and crystallographic planes
      (e.g., atomic arrangement, surface termination, surface charge) required to allow
      for strong preferential adsorption.

PMID- 16895390
TI  - Isotope-coded and affinity-tagged cross-linking (ICATXL): an efficient strategy
      to probe protein interaction surfaces.
AB  - Chemical cross-linking followed by identification of the cross-linked residues by
      mass spectrometry provides structural information on protein interaction
      surfaces. Nevertheless, accurate analysis of the digested, cross-linked proteins
      is often challenging. Herein, we describe a novel strategy that relies on the use
      of affinity-tagged cross-linkers and isotope coding on the cross-linker-modified
      species. Incorporation of O16 or O18 during the hydrolysis of the cross-linkers
      results in a characteristic "doublet" for the undesired products of a half-cross
      linking reaction. Therefore, genuine cross-linked peptides are readily
      distinguished for further structural analysis. This strategy permits a sensitive
      and facile analysis on a dimeric protease inhibitor, ecotin, showing general
      applicability to other protein assemblies.

PMID- 16895391
TI  - Scrambling of sequence information in collision-induced dissociation of peptides.
AB  - Collision-induced dissociation (CID) of protonated YAGFL-NH2 leads to nondirect
      sequence fragment ions that cannot directly be derived from the primary peptide
      structure. Experimental and theoretical evidence indicate that primary
      fragmentation of the intact peptide leads to the linear YAGFLoxa b5 ion with a C
      terminal oxazolone ring that is attacked by the N-terminal amino group to induce
      formation of a cyclic peptide b5 isomer. The latter can undergo various proton
      transfer reactions and opens up to form something other than the YAGFLoxa linear
      b5 isomer, leading to scrambling of sequence information in the CID of protonated
      YAGFL-NH2.

PMID- 16895392
TI  - What nonlinear-IR experiments can tell you about water that the IR spectrum
      cannot.
AB  - Frequently, the IR spectrum of water is used to characterize the structure and
      strength of the associated hydrogen bond network. Here, we use nonlinear-IR
      spectroscopy to investigate the dynamics of four aqueous systems that have very
      similar absorption spectra. We address the question: to what extent can the
      dynamics of water vary in systems with very similar absorption spectra? The
      results illustrate that the vibrational lifetimes and orientational relaxation
      time scales vary dramatically between the four samples and do not correlate with
      the amount of water relative to surfactant or solute in solution. Nonlinear-IR
      spectroscopies are therefore important for providing detailed information
      necessary to understand hydrogen bonded systems.

PMID- 16895393
TI  - Molecular mechanism for the cross-nucleation between polymorphs.
AB  - We use molecular simulations to study the early stages of crystallization in a
      supercooled liquid of Lennard-Jones particles. We observe the onset of
      concomitant polymorphism and demonstrate that this phenomenon results from the
      cross-nucleation of a metastable polymorph on the stable polymorph. We also show
      that cross-nucleation is selective as it only takes place between polymorphs of
      almost equivalent free energy. Our simulations provide detailed insights into the
      molecular mechanism underlying concomitant polymorphism and cross-nucleation
      between polymorphs.

PMID- 16895395
TI  - The dark side of crystal engineering: creating glasses from small symmetric
      molecules that form multiple hydrogen bonds.
AB  - Glasses made from compounds of low molecular weight are useful materials with
      many attractive features, including well-defined compositions. At present, there
      are no reliable ways to identify molecules that will form long-lived glasses, and
      efforts to design them have tended to rely on crude principles, such as avoiding
      small, symmetric, and relatively inflexible molecules that engage in strong
      intermolecular association. We have found that it is possible to make glasses
      from such molecules by turning to the dark side of crystal engineering and by
      making small but carefully selected structural modifications specifically
      designed to thwart established patterns of crystallization.

PMID- 16895394
TI  - Strain-release rearrangement of N-vinyl-2-arylaziridines. Total synthesis of the
      anti-leukemia alkaloid (-)-deoxyharringtonine.
AB  - Deoxyharringtonine (1) is among the most potent of the anti-leukemia alkaloids
      isolated from the Cephalotaxus genus. A convergent total synthesis of (-)-1 is
      reported, involving novel synthetic methods and strategies that include (1) the
      strain-release rearrangement of N-aryl-2-vinylaziridines for [3]benzazepine
      synthesis, (2) a vinylogous amide acylation-cycloaddition cascade for spiro
      pyrrolidine construction, and (3) efficient acylation of the cephalotaxine core
      by alpha-(beta-lactone)carboxylic acid derivatives to access the biologically
      active cephalotaxus esters. These innovations should allow rapid access not only
      to other Cephalotaxus alkaloids but also to non-natural analogues of potential
      therapeutic utility.

PMID- 16895396
TI  - Demonstration by 2H ENDOR spectroscopy that myo-inositol binds via an alkoxide
      bridge to the mixed-valent diiron center of myo-inositol oxygenase.
AB  - myo-Inositol oxygenase (MIOX) is a non-heme diiron oxygenase that cleaves
      cyclohexane-(1,2,3,5/4,6-hexa)-ol (myo-inositol, MI) to d-glucuronate. Here, we
      use 2H ENDOR spectroscopy to demonstrate that MI binds to the diiron(II/III)
      cofactor of MIOX via an alkoxide bridge, most likely involving O1. Analysis shows
      that MI adopts a symmetrical geometry in which the O-C-2H plane of the bridge is
      approximately orthogonal to the Fe-O-Fe plane.

PMID- 16895397
TI  - Microencapsulated linear polymers: "soluble" heterogeneous catalysts.
AB  - A new strategy for supporting catalysts based on the microencapsulation of linear
      polymers is presented. In this paper, we present a DMAP capsule that is capable
      of catalyzing acylation reactions. The catalyst is compared to DMAP on cross
      linked and linear polystyrene, as well as small molecule DMAP. Rapid optimization
      through modification of encapsulation conditions is demonstrated. The
      optimization provides a dynamic range of catalysis from 90 to 300% of the rate of
      DMAP on polystyrene.

PMID- 16895398
TI  - Synthesis and application of quantum dots FRET-based protease sensors.
AB  - Preparation of FRET-based quantum dots as protease sensors-RGDC peptide molecules
      are bound to the surface of CdSe/ZnS quantum dots. The peptide molecules are then
      labeled with rhodamine dye molecules. The emission color of the quantum dots
      change from green to orange due to fluorescence resonance energy transfer (FRET)
      between the quantum dots and the bound rhodamine molecules. Cleavage of the
      peptide by selective proteases releases the rhodamine molecules from the quantum
      dots surface, which results in decreasing FRET efficiency between the quantum
      dots and the rhodamine molecules. The emission color of the quantum dots changes
      back to green.

PMID- 16895399
TI  - Combinatorial synthesis of benzimidazolium dyes and its diversity directed
      application toward GTP-selective fluorescent chemosensors.
AB  - Highly selective fluorescence turn-on GTP sensor, GTP Green, was discovered by a
      diversity directed sensor approach, combined by solid-phase combinatorial
      synthesis of a benzimidazolium library and high-throughput screening.

PMID- 16895400
TI  - Bridged dihydroxypyridine ligands for the synthesis of expanded helicates.
AB  - The assembly of organometallic half-sandwich complexes with
      bis(dihydroxypyridine) ligands gives hexanuclear structures, which can be
      regarded as expanded triple-stranded helicates.

PMID- 16895401
TI  - Room temperature liquid fullerenes: an uncommon morphology of C60 derivatives.
AB  - Room temperature liquid C60 derivatives bearing a 2,4,6-trialkyloxyphenyl branch
      show a dramatic decrease in viscosity with an increase in the length of the alkyl
      chains. This feature, when combined with electrochemical activities similar to
      those of pristine C60 and relatively high charge carrier mobility, makes them an
      extremely attractive novel carbon material for future applications in materials
      science.

PMID- 16895403
TI  - Efficient templated synthesis of donor-acceptor rotaxanes using click chemistry.
AB  - The mild reaction conditions, remarkable functional group compatibility, and
      complete regioselectivity of the Cu-catalyzed Huisgen 1,3-dipolar cycloaddition
      ("click chemistry") between organic azides and terminal alkynes have led to a
      threading-followed-by-stoppering approach to the synthesis of donor-acceptor
      rotaxanes incorporating cyclobis(paraquat-p-phenylene) (CBPQT4+) as the pi
      accepting ring component. Rotaxane formation is initiated by reacting azide
      functionalized pseudorotaxanes containing pi-donating 1,5-dioxynaphthalene (DNP)
      recognition units with appropriate alkyne-functionalized stoppers. The high
      yields obtained in this efficient, kinetically controlled post-assembly covalent
      modification, as well as the excellent convergence of the synthetic protocol, are
      demonstrated by the preparation of [2]-, [3]-, and [4]rotaxanes containing
      multiple DNP/CBPQT4+ donor-acceptor recognition motifs.

PMID- 16895402
TI  - The bifunctional glyceryl transferase/phosphatase OzmB belonging to the HAD
      superfamily that diverts 1,3-bisphosphoglycerate into polyketide biosynthesis.
AB  - The HAD superfamily protein OzmB from the oxazolomycin biosynthetic pathway is
      shown to divert the primary metabolite 1,3-diphosphoglycerate into the polyketide
      biosynthetic pathway as glycerate via loading of a carrier protein. Each of the
      steps-activation of d-3-phosphoglycerate, dephosphorylation while attached to a
      cysteine on OzmB, and subsequent transfer of glycerate to the phosphopantetheinyl
      thiol of an acyl carrier protein-was monitored by nanospray Fourier transform
      mass spectrometry. This activation of phosphoglycerate represents a general
      mechanism of diverting glycolytic metabolites into glyceryl-derived polyketides.

PMID- 16895404
TI  - Experimental and theoretical studies of 45Sc NMR interactions in solids.
AB  - Solid-state 45Sc NMR spectroscopy, ab initio calculations, and X-ray
      crystallography are applied to examine the relationships between 45Sc NMR
      interactions and molecular structure and symmetry. Solid-state 45Sc (I = 7/2)
      magic-angle spinning (MAS) and static NMR spectra of powdered samples of
      Sc(acac)3, Sc(TMHD)3, Sc(NO3)3.5H2O, Sc(OAc)3, ScCl3.6H2O, ScCl3.3THF, and ScCp3
      have been acquired. These systems provide a variety of scandium coordination
      environments yielding an array of distinct 45Sc chemical shielding (CS) and
      electric field gradient (EFG) tensor parameters. Acquisition of spectra at two
      distinct magnetic fields allows for the first observations of scandium chemical
      shielding anisotropy (CSA). 45Sc quadrupolar coupling constants (CQ) range from
      3.9 to 13.1 MHz and correlate directly with the symmetry of the scandium
      coordination environment. Single-crystal X-ray structures were determined for
      Sc(TMHD)3, ScCl3.6H2O, and Sc(NO3)3.5H2O to establish the hitherto unknown
      scandium coordination environments. A comprehensive series of ab initio
      calculations of EFG and CS tensor parameters are in excellent agreement with the
      observed parameters. Theoretically determined orientations of the NMR interaction
      tensors allow for correlations between NMR tensor characteristics and scandium
      environments. Solid-state 45Sc, 13C, and 19F NMR experiments are also applied to
      characterize the structures of the microcrystalline Lewis acid catalyst Sc(OTf)3
      (for which the crystal structure is unknown) and a noncrystalline,
      microencapsulated, polystyrene-supported form of the compound.

PMID- 16895405
TI  - Microporous metal-organic frameworks formed in a stepwise manner from luminescent
      building blocks.
AB  - A series of trivalent lanthanides (Sm, Eu, Gd, Tb, Dy) have been complexed to the
      dianionic ligand, 4,4'-disulfo-2,2'-bipyridine-N,N'-dioxide, L, in a 3:1 ratio to
      form trianionic complex building blocks. These units were then cross-linked into
      a network solid by addition of BaCl2 to form mixed-metal networks of formula
      {Ba2(H2O)4[LnL3(H2O)2](H2O)nCl}infinity, Ln = Sm3+ (1), Eu3+ (2), Gd3+ (3), Tb3+
      (4), Dy3+ (5). The networks were isostructural and contained open channels which
      readily absorbed and desorbed water accompanied by a spongelike shrinkage and
      expansion of the host. CO2 sorption measurements confirmed microporosity giving a
      DR surface area of 718 m2/gm and an average pore size of 6.4 A. Ligand L
      sensitized all the lanthanide ions with the exception of Gd3+. Studying the
      series of Ln complexes allowed the determination of the triplet state energy of L
      which is itself a new ligand for sensitization purposes. The luminescent
      properties of the lanthanide building blocks were retained in the porous network
      solid. From the luminescence data, it was possible to attribute the spongelike
      properties of the network to the Ba2+ coordination sphere rather than the Ln3+
      center. Networks were characterized by X-ray crystallography, PXRD, DSC/TGA,
      water vapor and gas sorption, and luminescence spectroscopy.

PMID- 16895406
TI  - A fluorescent lectin array using supramolecular hydrogel for simple detection and
      pattern profiling for various glycoconjugates.
AB  - Because sugar and its derivatives play important roles in various biological
      phenomena, the rapid and high-throughput analysis of various glycoconjugates is
      keenly desirable. We describe herein the construction of a novel fluorescent
      lectin array for saccharide detection using a supramolecular hydrogel matrix. In
      this array, the fluorescent lectins were noncovalently fixed under semi-wet
      conditions to suppress the protein denaturation. It is demonstrated by
      fluorescence titration and fluorescence lifetime experiments that the immobilized
      lectins act as a molecular recognition scaffold in the hydrogel matrix, similar
      to that in aqueous solution. That is, a bimolecular fluorescence quenching and
      recovery (BFQR) method can successfully operate under both conditions. This
      enables one to fluorescently read-out a series of saccharides on the basis of the
      recognition selectivity and affinity of the immobilized lectins without tedious
      washing processes and without labeling the target saccharides. Simple and high
      throughput sensing and profiling were carried out using the present lectin array
      for diverse glycoconjugates, which not only included a simple glucose, but also
      oligosaccharides, and glycoproteins, and, furthermore, the pattern recognition
      and profiling of several types of cell lysates were also accomplished.

PMID- 16895408
TI  - Electronic coupling and exciton energy transfer in CdTe quantum-dot molecules.
AB  - Stable dispersions of molecularlike aggregates of CdTe quantum dots are prepared
      by chemical cross-linking. Cryo-TEM images confirm the presence of cross-linked
      quantum dots and show that the size of the small aggregates can be controlled by
      the amount of cross-linker added. Optical measurements reveal two types of
      interdot interactions within these quantum-dot molecules: exciton energy transfer
      and electronic coupling. Quantitative information on the energy transfer rates in
      quantum-dot molecules is obtained by photoluminescence lifetime measurements. The
      degree of electronic coupling is dependent on the size of the quantum dots, which
      is supported by quantum mechanical calculations.

PMID- 16895407
TI  - Ethyne-bridged (porphinato)zinc(II)-(porphinato)iron(III) complexes:
      phenomenological dependence of excited-state dynamics upon (porphinato)iron
      electronic structure.
AB  - We report the synthesis, spectroscopy, potentiometric properties, and excited
      state dynamical studies of 5-[(10,20-di-((4-ethyl ester)methylene
      oxy)phenyl)porphinato]zinc(II)-[5'-[(10',20'- di-((4-ethyl ester)methylene
      oxy)phenyl)porphinato]iron(III)-chloride]ethyne (PZn-PFe-Cl), along with a series
      of related supermolecules ([PZn-PFe-(L)1,2]+ species) that possess a range of
      metal axial ligation environments (L = pyridine, 4-cyanopyridine, 2,4,6
      trimethylpyridine (collidine), and 2,6-dimethylpyridine (2,6-lutidine)). Relevant
      monomeric [(porphinato)iron-(ligand)1,2]+ ([PFe(L)1,2]+) benchmarks have also
      been synthesized and fully characterized. Ultrafast pump-probe transient
      absorption spectroscopic experiments that interrogate the initially prepared
      electronically excited states of [PFe(L)1,2]+ species bearing nonhindered axial
      ligands demonstrated subpicosecond-to-picosecond relaxation dynamics to the
      ground electronic state. Comparative pump-probe transient absorption experiments
      that interrogate the initially prepared excited states of PZn-PFe-Cl, [PZn-PFe
      (py)2]+, [PZn-PFe-(4-CN-py)2]+, [PZn-PFe-(collidine)]+, and [PZn-PFe-(2,6
      lutidine)]+ demonstrate that the spectra of all these species are dominated by a
      broad, intense NIR S1 --> Sn transient absorption manifold. While PZn-PFe-Cl,
      [PZn-PFe-(py)2]+, and [PZn-PFe-(4-CN-py)2]+ evince subpicosecond and picosecond
      time-scale relaxation of their respective initially prepared electronically
      excited states to the ground state, the excited-state dynamics observed for [PZn
      PFe-(2,6-lutidine)]+ and [PZn-PFe-(collidine)]+ show fast relaxation to a [PZn+
      PFe(II)] charge-separated state having a lifetime of nearly 1 ns. Potentiometric
      data indicate that while DeltaGCS for [PZn-PFe-(L)1,2]+ species is strongly
      influenced by the PFe+ ligation state [ligand (DeltaGCS): 4-cyanopyridine (-0.79
      eV) < pyridine (-1.04 eV) < collidine (-1.35 eV) < chloride (-1.40 eV); solvent =
      CH2Cl2], the pump-probe transient absorption dynamical data demonstrate that the
      nature of the dominant excited-state decay pathway is not correlated with the
      thermodynamic driving force for photoinduced charge separation, but depends on
      the ferric ion ligation mode. These data indicate that sterically bulky axial
      ligands that drive a pentacoordinate PFe center and a weak metal axial ligand
      interaction serve to sufficiently suppress the normally large magnitude
      nonradiative decay rate constants characteristic of (porphinato)iron(III)
      complexes, and thus make electron transfer a competitive excited-state
      deactivation pathway.

PMID- 16895409
TI  - Fe L-edge XAS studies of K4[Fe(CN)6] and K3[Fe(CN)6]: a direct probe of back
      bonding.
AB  - Distinct spectral features at the Fe L-edge of the two compounds K3[Fe(CN)6] and
      K4[Fe(CN)6] have been identified and characterized as arising from contributions
      of the ligand pi orbitals due to metal-to-ligand back-bonding. In addition, the L
      edge energy shifts and total intensities allow changes in the ligand field and
      effective nuclear charge to be determined. It is found that the ligand field term
      dominates the edge energy shift. The results of the experimental analysis were
      compared to BP86 DFT calculations. The overall agreement between the calculations
      and experiment is good; however, a larger difference in the amount of pi back
      donation between Fe(II) and Fe(III) is found experimentally. The analysis of L
      edge spectral shape, energy shift, and total intensity demonstrates that Fe L
      edge X-ray absorption spectroscopy provides a direct probe of metal-to-ligand
      back-bonding.

PMID- 16895410
TI  - Oligo-Asp tag/Zn(II) complex probe as a new pair for labeling and fluorescence
      imaging of proteins.
AB  - To accomplish the selective labeling of a specific protein in complicated
      biological systems, a peptide tag incorporated into the protein and a
      complementary small molecular probe are required. Although a variety of peptide
      tag/probe pairs have been developed as molecular tools for protein analyses, the
      availability of pairs suitable for real-time imaging of proteins is still
      limited. We now report a new peptide tag/artificial probe pair composed of a
      genetically encodable oligo-aspartate sequence (D4 tag, (D4)n, n = 1-3) and the
      corresponding multinuclear Zn(II) complexes (Zn(II)-DpaTyrs). The strong binding
      affinity of the Zn(II)-DpaTyr probes with the D4 tag was a result of the multiple
      coordination bonds and the multivalent effect. It was measured quantitatively by
      isothermal titration calorimetry. The high affinity between the tag and the
      probe, indispensable for the selective protein labeling, enabled the pair to be
      used for the labeling and fluorescence imaging of a membrane-bound receptor
      protein tethering a triply repeated D4 tag ((D4)3) in an intact cell
      configuration without significantly affecting the receptor signal transduction.

PMID- 16895411
TI  - On the origin of helical mesostructures.
AB  - The investigation on the formation mechanism of helical structures and the
      synthesis of helical materials is attractive for scientists in different fields.
      Here we report the synthesis of helical mesoporous materials with chiral channels
      in the presence of achiral surfactants. More importantly, we suggest a simple and
      purely interfacial interaction mechanism to explain the spontaneous formation of
      helical mesostructures. Unlike the proposed model for the formation of helical
      molecular chains or surpramolecular packing based on the geometrically motivated
      model or the entropically driven model, the origin of the helical mesostructured
      materials may be attributed to a morphological transformation accompanied by a
      reduction in surface free energy. After the helical morphology is formed, the
      increase in bending energy together with the derivation from a perfect hexagonal
      mesostructure may limit the curvature of helices. Our model may be general and
      important in the designed synthesis of helical mesoporous materials.

PMID- 16895412
TI  - Conformational flexibility in hydrated sugars: the glycolaldehyde-water complex.
AB  - Conformational flexibility in the smallest hydrated sugar, the glycolaldehyde
      water complex, has been investigated in the gas phase by means of a combination
      of a microwave Fourier transform spectroscopy experiment in a supersonic
      molecular beam and ab initio quantum chemistry calculations. The water molecule
      inserts into glycolaldehyde using H-bonding selectivity: the two lowest energy
      conformations are stabilized by two intermolecular hydrogen bonds, and the next
      two by one intra- plus one intermolecular hydrogen bond. A dynamical flexibility
      associated with the two lowest energy conformations has been experimentally
      observed and accurately modeled with a two-dimensional potential energy surface
      involving the hydroxyl group and the free OH water group coordinates. The
      conclusions drawn from the role played in the conformational flexibility by the
      hydroxyl and carbonyl groups are extended to other carbohydrates and
      biomolecules.

PMID- 16895414
TI  - Extreme conformational constraints in pi-extended tetrathiafulvalenes: unusual
      topologies and redox behavior of doubly and triply bridged cyclophanes.
AB  - Doubly and triply bridged 9,10-bis(1,3-dithiol-2-ylidene)-9,10-dihydroanthracene
      (ex-TTF) derivatives have been synthesized. Key steps are the generation and
      macrocyclization reactions of ex-TTF-dithiolate reagents. The X-ray crystal
      structures of the doubly bridged cyclophanes 15 and 16 and the triply bridged
      system 23 show that the saddle-like conformation of the ex-TTF framework is
      enhanced by the short bridges between the dithiole rings. Unlike all previous ex
      TTF derivatives (which display a single quasi-reversible two-electron oxidation
      wave, D0 --> D2+), cyclic voltammetry of the cyclophanes reveals two reversible,
      one-electron oxidation steps (D0 --> D*+ --> D2+), with differences between the
      half-wave potentials (E2(1/2) - E1(1/2)) of 0.22-0.26 V. The conformational
      changes and gain in aromaticity which drive the second oxidation process in
      unrestricted ex-TTF systems (including singly bridged cyclophanes) have been
      prevented by multiple bridging. The radical cation species gives rise to a very
      broad, low-energy band (lambdamax = 2175 and 2040 nm for 15 and 21,
      respectively), assigned to an intramolecular interaction. The steric constraints
      imposed by multiple bridging have become so extreme that the pi-framework of 15,
      16, 21, and 23 exhibits remarkable optical and redox behavior which is not
      characteristic of ex-TTF systems.

PMID- 16895413
TI  - Spectroscopic determination of proton position in the proton-coupled electron
      transfer pathways of donor-acceptor supramolecule assemblies.
AB  - A homologous set of porphyrin derivatives possessing an isocyclic five-membered
      ring appended with an amidinium functionality has been used to examine proton
      coupled electron transfer (PCET) through well-characterized amidine-carboxylic
      acid interfaces. Conjugation between the porphyrin chromophore and the amidinium
      interface can be altered by selective reduction of the isocyclic ring of an
      amidinium-purpurin to produce an amidinium-chlorin. The highly conjugated
      amidinium-purpurin displays large spectral shifts in the visible region upon
      alteration of the amidinium/amidine protonation state; no such change is observed
      for the chlorin homologue. Analysis of the UV-vis absorption and emission
      profiles of the amidinium-purpurin upon deprotonation allows for the measurement
      of the porphyrinic-amidinium acidity constant for the ground state (pKa = 9.55 +/
      0.1 in CH3CN) and excited state (pKa)= 10.40 +/- 0.1 in CH3CN). The absorption
      spectrum of the purpurin also provides a convenient handle for determining the
      protonation state of assembled interfaces. In this way, the purpurin macrocycle
      provides a general tool for PCET studies because it can be used to determine the
      location of a proton within PCET interfaces formed from carboxylic acid electron
      acceptors including dinitrobenzenes (DNBs) and naphthalenediimide (NI), which
      have been used extensively in previous PCET studies. An amidine-carboxylic acid
      interface is observed for electron-rich acceptors, whereas the ionized amidinium
      carboxylate interface is observed for electron-poor acceptors. The PCET kinetics
      for purpurin/chlorin associated to NI are consistent with an amidine-carboxylic
      acid interface, which is also verified spectrally.

PMID- 16895415
TI  - Total synthesis and structural confirmation of chlorodysinosin A.
AB  - The first enantiocontrolled total synthesis of the marine sponge metabolite
      chlorodysinosin A is described. The structure and absolute configuration are
      identical to those of dysinosin A except for the presence of a novel 2S,3R-3
      chloroleucine residue in the former. A concise stereocontrolled synthesis of the
      new chlorine-containing amino acid fragment was developed. An X-ray cocrystal
      structure of synthetic chlorodysinosin A with the enzyme thrombin confirms the
      structure and configuration assignment achieved through total synthesis. Within
      the aeruginosin family of natural products, chlorodysinosin A is the most potent
      inhibitor of the serine proteases thrombin, factor VIIa, and factor Xa, which are
      critical enzymes in the process leading to platelet aggregation and fibrin mesh
      formation in humans.

PMID- 16895416
TI  - Electron self-exchange between Au140(+/0) nanoparticles is faster than that
      between Au38(+/0) in solid-state, mixed-valent films.
AB  - The well-defined one-electron steps in the voltammetry of solutions of the
      nanoparticles Au38(SC2Ph)24 and Au140(SC6)53 (SC2Ph = phenylethanethiolate; SC6 =
      hexanethiolate) enable preparation of solutions containing, for example,
      Au38(SC2Ph)24 and Au38(SC2Ph)24+(ClO4)- nanoparticles in known relative
      proportions. From these solutions can be cast dry, mixed-valent films
      demonstrably containing the same proportions. Electronic conduction in such mixed
      valent films is shown to occur by a bimolecular electron self-exchange reaction
      at a rate proportional to the concentration product, [Au38][Au38+]. The observed
      Au38(+/0) rate constant, approximately 2 x 10(6) M(-1) s(-1), is much smaller
      than that previously observed for Au140(+/0) films (ca. 4 x 10(9) M(-1) s(-1);
      Wuelfing, W. P.; et al. J. Am. Chem. Soc. 2000, 122, 11465). To our knowledge,
      this is the first example of a significant size effect in metal nanoparticle
      electron-transfer dynamics. Thermal activation parameters for the electron
      hopping conductivities of the two nanoparticles reveal that the rate difference
      is mainly caused by energy barriers (EA) for Au38(+/0) electron transfers that
      are larger by approximately 3-fold than those for Au140(+/0) electron transfers
      (ca. 20 vs 7 kJ/mol). Differences in pre-exponential terms in the activation
      equations for the two nanoparticles are a smaller contributor to the rate
      constant difference and can be partly ascribed to differences in tunneling
      distances.

PMID- 16895417
TI  - Modulating rhodopsin receptor activation by altering the pKa of the retinal
      Schiff base.
AB  - The visual pigment rhodopsin is a seven-transmembrane (7-TM) G protein-coupled
      receptor (GPCR). Activation of rhodopsin involves two pH-dependent steps: proton
      uptake at a conserved cytoplasmic motif between TM helices 3 and 6, and
      disruption of a salt bridge between a protonated Schiff base (PSB) and its
      carboxylate counterion in the transmembrane core of the receptor. Formation of an
      artificial pigment with a retinal chromophore fluorinated at C14 decreases the
      intrinsic pKa of the PSB and thereby destabilizes this salt bridge. Using Fourier
      transform infrared difference and UV-visible spectroscopy, we characterized the
      pH-dependent equilibrium between the active photoproduct Meta II and its inactive
      precursor, Meta I, in the 14-fluoro (14-F) analogue pigment. The 14-F chromophore
      decreases the enthalpy change of the Meta I-to-Meta II transition and shifts the
      Meta I/Meta II equilibrium toward Meta II. Combining C14 fluorination with
      deletion of the retinal beta-ionone ring to form a 14-F acyclic artificial
      pigment uncouples disruption of the Schiff base salt bridge from transition to
      Meta II and in particular from the cytoplasmic proton uptake reaction, as
      confirmed by combining the 14-F acyclic chromophore with the E134Q mutant. The 14
      F acyclic analogue formed a stable Meta I state with a deprotonated Schiff base
      and an at least partially protonated protein counterion. The combination of
      retinal modification and site-directed mutagenesis reveals that disruption of the
      protonated Schiff base salt bridge is the most important step thermodynamically
      in the transition from Meta I to Meta II. This finding is particularly important
      since deprotonation of the retinal PSB is known to precede the transition to the
      active state in rhodopsin activation and is consistent with models of agonist
      dependent activation of other GPCRs.

PMID- 16895418
TI  - Rational design of bacitracin A derivatives by incorporating natural product
      derived heterocycles.
AB  - Heterocycles display common structural motifs in nonribosomally produced peptides
      with an enormous impact on their bioactivity. In the case of the branched cyclic
      Bacitracin A, the thiazoline moiety is manufactured during NRPS peptide chain
      elongation. Here we describe a method to selectively alter the heterocyclic metal
      binding subunit of Bacitracin A by the synthesis of heterocyclic building blocks
      that were successfully coupled to the linear decapeptide and subsequently
      cyclized using the excised bacitracin PCP-TE bidomain. Utilization of this
      cyclase allowed the first generation of branched cyclic bacitracin derivatives
      containing thiazole and oxazoles. The generated bacitracin derivatives showed
      bactericidal activity, indicating the possibility of altering the biological
      important heterocyclic subunit and overcoming existing limitations for the
      application of bacitracin.

PMID- 16895419
TI  - Development of an ab initio emulsion atom transfer radical polymerization: from
      microemulsion to emulsion.
AB  - Atom transfer radical polymerization (ATRP) has been successfully extended to an
      ab initio emulsion system using a "two-step" procedure, in which the final
      emulsion polymerization system was formed by adding monomer to an ongoing
      microemulsion ATRP. The newly developed AGET (activators generated by electron
      transfer) initiation technique was employed in the first stage of this ab initio
      ATRP. It allows using oxidatively stable Cu(II) species that is reduced in situ
      by ascorbic acid. The surfactant concentration in the final emulsion system was
      efficiently decreased to approximately 2 wt % (approximately 10 wt % vs monomer)
      by decreasing the catalyst concentration and changing the ratio of the monomer
      added at the microemulsion stage to the monomer added during the second stage.
      This two-step procedure avoids the necessity of transporting catalysts through
      the aqueous media during polymerization, resulting in a controlled emulsion
      polymerization, as evidenced by a linear first-order kinetic plot and formation
      of a polymer with a relatively narrow molecular weight distribution (Mw/Mn = 1.2
      1.4). The polymerization typically reached 70-90% monomer conversion in 5-6 h.
      The resulting polymer had high chain-end functionality and was successfully chain
      extended to form in situ block copolymers by adding the second monomer to an
      ongoing emulsion polymerization. The stable latex from the ab initio emulsion
      ATRP had a particle size approximately 120 +/- 10 nm.

PMID- 16895420
TI  - Construction of segregated arrays of multiple donor and acceptor units using a
      dendritic scaffold: remarkable dendrimer effects on photoinduced charge
      separation.
AB  - Dendritic molecules appended with multiple zinc porphyrin units (DPm, m [number
      of zinc porphyrin units] = 6, 12, and 24) trap bipyridine compounds carrying
      multiple fullerene units (Py2Fn, n [number of C60 units] = 1-3), affording
      coordination complexes DPm superset Py2Fn having a photoactive layer consisting
      of spatially segregated donor and acceptor arrays on their surface. Complexes DPm
      superset Py2Fn are stable enough (K [average binding affinity] = 1.1 x 10(6)-4.4
      x 10(6) M(-1) in CHCl3 at 25 degrees C) to be isolated by gel permeation
      chromatography. UHV-STM microscopy enables clear visualization of a petal-like
      structure of DP12 superset Py2F3. Photoexcitation of the zinc porphyrin units in
      DPm superset Py2Fn results in a zinc porphyrin-to-fullerene electron transfer to
      generate a charge separation. The charge-separation rate constant (kCS) in CH2Cl2
      at 20 degrees C increases from 0.26 x 10(10) to 2.3 x 10(10) s(-1) upon increment
      of m and n, whereas the charge-recombination rate constant (kCR) remains almost
      unchanged at 4.5 x 10(6)-6.7 x 10(6) s(-1). Consequently, DP24 supersetPy2F3
      furnishes the largest ratio of kCS/kCR (3400) among the family.

PMID- 16895421
TI  - Photochemical reactivity of 2-vinylbiphenyl and 2-vinyl-1,3-terphenyl: the
      balance between nonadiabatic and adiabatic photocyclization.
AB  - A mechanism for the photochemical conversion of 2-vinyl-1,3-terphenyl to 8,9a
      dihydrophenanthrene (Lewis, F. D.; Zuo, X.; Gevorgyan, V.; Rubin, M. J. Am. Chem.
      Soc. 2002, 124, 13664-13665) is presented in this study, based on ab initio
      restricted active space self-consistent field calculations and a molecular
      mechanics-valence bond dynamics simulation of a model system: the syn isomer of 2
      vinylbiphenyl. An extended crossing seam between the ground and first excited
      electronic states was found to be largely responsible for the efficient
      photocyclization of the photochemically active syn isomer. This mechanism is
      nonadiabatic in nature, with an excited-state reaction pathway approaching the
      crossing region during the initial stage of cyclization. Dynamics simulation
      shows that this seam is easily accessible by vibrational motion in the branching
      space, once a small barrier is passed on the S1 excited-state potential energy
      surface. Ultrafast radiationless decay to the ground state then follows, and the
      cyclization is completed on this surface. A second possible mechanism was
      identified, which involves complete adiabatic cyclization on the S1 surface, with
      decay to the ground state (at a different conical intersection) only taking place
      once the product is formed. Thus, there is a competition between these two
      mechanisms-nonadiabatic and adiabatic-governed by the dynamics of the system. A
      large quantum yield is predicted for the photocyclization of the syn isomer of 2
      vinylbiphenyl and 2-vinyl-1,3-terphenyl, in agreement with experimental
      observations.

PMID- 16895422
TI  - Competition between protein ligands and cytoplasmic inorganic anions for the
      metal cation: a DFT/CDM study.
AB  - Many of the essential metalloproteins are located in the cell, whose cytoplasmic
      fluid contains several small inorganic anions, such as Cl-, NO2-, NO3-, H2PO4-,
      and SO4(2-), that play an indispensable role in determining the cell's volume,
      regulating the cell's pH, signal transduction, muscle contraction, as well as
      cell growth and metabolism. However, the physical principles governing the
      competition between these abundant, intracellular anions and protein or nucleic
      acid residues in binding to cytoplasmic metal cations such as Na+, K+, Mg2+, and
      Ca2+ are not well understood; hence, we have delineated the physicochemical basis
      for this competition using density functional theory in conjunction with the
      continuum dielectric method. The results show that the metal cation can bind to
      its target protein against a high background concentration of inorganic anions
      because (i) desolvating a negatively charged Asp/Glu carboxylate in a protein
      cavity costs much less than desolvating an inorganic anion in aqueous solution
      and (ii) the metal-binding site acts as a polydentate ligand that uses all its
      ligating entities to bind the metal cation either directly or indirectly. The
      results also show that the absolute hydration free energy of the "alien" anion as
      well as the net charge and relative solvent exposure of the metal-binding protein
      cavity are the key factors governing the competition between protein and
      inorganic ligands for a given cytoplasmic metal cation. Increasing the net
      negative charge of the protein cavity, while decreasing the number of available
      amide groups for metal binding, protects the metal-bound ligands from being
      dislodged by cellular anions, thus revealing a "protective" role for carboxylate
      groups in a protein cavity, in addition to their role in high affinity metal
      binding.

PMID- 16895423
TI  - Synthesis and reactivity of the imido analogues of the uranyl ion.
AB  - Addition of 1.5 equiv of I2 to a THF solution of UI3(THF)4, containing either 6
      equiv of tBuNH2 or 2 equiv of RNH2 (R = Ph, 3,5-(CF3)2C6H3, 2,6-(iPr)2C6H3) and 4
      equiv of NEt3, generates orange solutions containing U(NtBu)2I2(THF)2 (1) or
      U(NAr)2I2(THF)3 (Ar = Ph, 2; 3,5-(CF3)2C6H3, 3; 2,6-(iPr)2C6H3, 4), respectively,
      all of which can be isolated in good yields. Alternatively, 1 can be prepared by
      reaction of uranium metal with 3 equiv of I2 and 6 equiv of tBuNH2, also in good
      yield. Complexes 1-4 have been characterized by X-ray crystallography, and each
      of these complexes exhibits linear N-U-N linkages and short U-N bonds. Using
      density functional theory simulations of complexes 1 and 2, two triple bonds
      between the metal center and the nitrogen ligands were identified. Complexes 1
      and 2 readily react with neutral Lewis bases such as pyridine or Ph3PO to form
      U(NR)2I2(L)2 (R = tBu, L = py, 5; Ph3PO, 7; R = Ph, L = py, 6; Ph3PO, 8), and
      with PMe3 to form U(NR)2I2(THF)(PMe3)2 (R = tBu, 9; Ph, 10). The solid-state
      molecular structures of 5, 7, and 9 have been determined by X-ray
      crystallography, and these complexes, like their parent compounds, exhibit linear
      N-U-N angles and short U-N bonds. Complexes 1 and 2 also react with AgOTf in
      CH2Cl2, forming U(NR)2(OTf)2(THF)3 (R = tBu, 11; Ph, 12) after recrystallization
      from THF. Crystals of 12 grown from CH2Cl2 were found to contain a dimer,
      [U(NPh)2(OTf)2(THF)2]2, a complex possessing bridging triflate groups.

PMID- 16895424
TI  - Nanosphere and nanonetwork formations of [60]fullerene-end-capped stereoregular
      poly(methyl methacrylate)s through stereocomplex formation combined with self
      assembly of the fullerenes.
AB  - We report a novel and versatile method for constructing a supramolecular
      nanosphere and nanonetwork based on isotactic and syndiotactic C60-end-capped
      poly(methyl methacrylate)s (it- and st-PMMA-C60's) through their stereocomplex
      formation combined with self-assembly of the terminal C60. The stereoregular PMMA
      C60's with a precisely controlled structure including molecular weight, its
      distribution, tacticity, and the chain-end structure were synthesized by the
      stereospecific anionic living polymerizations of methyl methacrylate followed by
      end-capping with C60, and their structures were proven by size exclusion
      chromatography, NMR, UV-vis, and MALDI-TOF-MS analyses. The stereoregular PMMA
      C60's self-assembled to form a core-shell aggregate with C60 as the core and the
      PMMA chains as the shell in H2O/CH3CN (1/9, v/v) due to the solvophobic
      interaction of the C60 units. These it- and st-PMMA-C60 aggregates further
      supramolecularly assembled through iterative stereocomplex formation into
      nanonetworks in which the self-assembled C60 clusters were robustly connected
      with two- and three-dimensional arrangements. In addition, when the it- and st
      PMMA-C60's were simultaneously mixed, self-assembly of the C60 units and
      stereocomplex formation of the it- and st-PMMA chains took place at once,
      resulting in the formation of uniformly sized spherical nanoparticles with
      resistance to heat. Similar nanonetwork architectures can be produced using it
      PMMA-C60 clusters and st-PMMA prepolymers as the binder.

PMID- 16895425
TI  - Soluble ultra-short single-walled carbon nanotubes.
AB  - Soluble, ultra-short (length < 60 nm), carboxylated, single-walled carbon
      nanotubes (SWNTs) have been prepared by a scalable process. This process,
      predicated on oleum's (100% H2SO4 with excess SO3) ability to intercalate between
      individual SWNTs inside SWNT ropes, is a procedure that simultaneously cuts and
      functionalizes SWNTs using a mixture of sulfuric and nitric acids. The solubility
      of these ultra-short SWNTs (US-SWNTs) in organic solvents, superacid and water is
      about 2 wt %. The availability of soluble US-SWNTs could open opportunities for
      forming high performance composites, blends, and copolymers without inhibiting
      their processibility.

PMID- 16895426
TI  - Toward the development of a general chiral auxiliary. A total synthesis of (+)
      tetronolide via a tandem ketene-trapping [4 + 2] cycloaddition strategy.
AB  - A highly convergent, enantioselective total synthesis of the aglycone of the
      tetrocarcins, (+)-tetronolide, is described. The synthesis highlights the use of
      several new methods, including camphor auxiliary-directed asymmetric alkylation
      and the enantioselective preparation of acyclic mixed acetals bearing chirality
      at the acetal center, and the highly efficient connection of the two major
      precursors via a ketene-trapping/intramolecular [4 + 2] cycloaddition strategy.

PMID- 16895429
TI  - Gold metal-catalyzed reactions of isocyanides with primary amines and oxygen:
      analogies with reactions of isocyanides in transition metal complexes.
AB  - Despite its generally poor catalytic properties, bulk gold metal is observed to
      catalyze reactions of isocyanides (CN-R) with primary amines (H2N-R') and O2 to
      give carbodiimides (R-N=C=N-R') at room temperature and above. Detailed infrared
      reflection absorption spectroscopic (IRRAS) and kinetic studies show that the
      reaction occurs by initial eta1-adsorption of the isocyanide on the Au surface,
      which activates the isocyanide to attack by the amine. This attack is the rate
      determining step in the catalytic cycle and has characteristics very similar to
      those of amine reactions with coordinated isocyanides in transition metal
      complexes. However, the metallic Au surface provides a pathway involving O2 to
      give the carbodiimide product whereas homogeneous metal ion catalysts give
      formamidines [HC(=NR)(NHR')].

PMID- 16895427
TI  - Intramolecular diels-alder/1,3-dipolar cycloaddition cascade of 1,3,4
      oxadiazoles.
AB  - Full details of a systematic exploration of the intramolecular [4 + 2]/[3 + 2]
      cycloaddition cascade of 1,3,4-oxadiazoles are disclosed in which the scope and
      utility of the reaction are defined.

PMID- 16895430
TI  - Cooperative hydration of pyruvic acid in ice.
AB  - About 3.5 +/- 0.3 water molecules are still involved in the exothermic hydration
      of 2-oxopropanoic acid (PA) into its monohydrate (2,2-dihydroxypropanoic acid,
      PAH) in ice at 230 K. This is borne out by thermodynamic analysis of the fact
      that QH(T) = [PAH]/[PA] becomes temperature independent below approximately 250 K
      (in chemically and thermally equilibrated frozen 0.1 < or = [PA]/M < or = 4.6
      solutions in D2O), which requires that the enthalpy of PA hydration (DeltaHH
      approximately -22 kJ mol(-1)) be balanced by a multiple of the enthalpy of ice
      melting (DeltaHM = 6.3 kJ mol(-1)). Considering that: (1) thermograms of frozen
      PA solutions display a single endotherm, at the onset of ice melting, (2) the sum
      of the integral intensities of the 1deltaPAH and 1deltaPA methyl proton NMR
      resonances is nearly constant while, (3) line widths increase exponentially with
      decreasing temperature before diverging below approximately 230 K, we infer that
      PA in ice remains cooperatively hydrated within interstitial microfluids until
      they vitrify.

PMID- 16895428
TI  - Total synthesis of (-)- and ent-(+)-vindoline and related alkaloids.
AB  - A concise 11-step total synthesis of (-)- and ent-(+)-vindoline (3) is detailed
      based on a unique tandem intramolecular [4 + 2]/[3 + 2] cycloaddition cascade of
      a 1,3,4-oxadiazole inspired by the natural product structure, in which three
      rings and four C-C bonds are formed central to the characteristic pentacyclic
      ring system setting all six stereocenters and introducing essentially all the
      functionality found in the natural product in a single step. As key elements of
      the scope and stereochemical features of the reaction were defined, a series of
      related natural products of increasing complexity were prepared by total
      synthesis including both enantiomers of minovine (4), 4-desacetoxy-6,7
      dihydrovindorosine (5), 4-desacetoxyvindorosine (6), and vindorosine (7) as well
      as N-methylaspidospermidine (11). Subsequent extensions of the approach provided
      both enantiomers of 6,7-dihydrovindoline (8), 4-desacetoxyvindoline (9), and 4
      desacetoxy-6,7-dihydrovindoline (10).

PMID- 16895431
TI  - A binary DNA probe for highly specific nucleic Acid recognition.
AB  - A new concept for nucleic acid probe design is reported. The extremely high
      selectivity of the probe is predetermined by cooperative hybridization of the two
      relatively short (10 nucleotide) DNA hairpin fragments to the analyte. A binary
      DNA probe fluorescently reports the presence of 0.5% of the analyte in excess
      amount of a single base substituted oligodeoxyribonucleotide and distinguishes
      single nucleotide substitutions at any position of a 20-mer oligonucleotide at
      room temperature.

PMID- 16895434
TI  - Insights into the coupling of duplication events and macroevolution from an age
      profile of animal transmembrane gene families.
AB  - The evolution of new gene families subsequent to gene duplication may be coupled
      to the fluctuation of population and environment variables. Based upon that, we
      presented a systematic analysis of the animal transmembrane gene duplication
      events on a macroevolutionary scale by integrating the palaeontology repository.
      The age of duplication events was calculated by maximum likelihood method, and
      the age distribution was estimated by density histogram and normal kernel density
      estimation. We showed that the density of the duplicates displays a positive
      correlation with the estimates of maximum number of cell types of common
      ancestors, and the oxidation events played a key role in the major transitions of
      this density trace. Next, we focused on the Phanerozoic phase, during which more
      macroevolution data are available. The pulse mass extinction timepoints coincide
      with the local peaks of the age distribution, suggesting that the transmembrane
      gene duplicates fixed frequently when the environment changed dramatically.
      Moreover, a 61-million-year cycle is the most possible cycle in this phase by
      spectral analysis, which is consistent with the cycles recently detected in
      biodiversity. Our data thus elucidate a strong coupling of duplication events and
      macroevolution; furthermore, our method also provides a new way to address these
      questions.

PMID- 16895435
TI  - Matrix formalism to describe functional states of transcriptional regulatory
      systems.
AB  - Complex regulatory networks control the transcription state of a genome. These
      transcriptional regulatory networks (TRNs) have been mathematically described
      using a Boolean formalism, in which the state of a gene is represented as either
      transcribed or not transcribed in response to regulatory signals. The Boolean
      formalism results in a series of regulatory rules for the individual genes of a
      TRN that in turn can be used to link environmental cues to the transcription
      state of a genome, thereby forming a complete transcriptional regulatory system
      (TRS). Herein, we develop a formalism that represents such a set of regulatory
      rules in a matrix form. Matrix formalism allows for the systemic characterization
      of the properties of a TRS and facilitates the computation of the transcriptional
      state of the genome under any given set of environmental conditions.
      Additionally, it provides a means to incorporate mechanistic detail of a TRS as
      it becomes available. In this study, the regulatory network matrix, R, for a
      prototypic TRS is characterized and the fundamental subspaces of this matrix are
      described. We illustrate how the matrix representation of a TRS coupled with its
      environment (R*) allows for a sampling of all possible expression states of a
      given network, and furthermore, how the fundamental subspaces of the matrix
      provide a way to study key TRS features and may assist in experimental design.

PMID- 16895436
TI  - Identification of mitochondrial DNA polymorphisms that alter mitochondrial matrix
      pH and intracellular calcium dynamics.
AB  - Mitochondrial DNA (mtDNA) is highly polymorphic, and its variations in humans may
      contribute to individual differences in function as well as susceptibility to
      various diseases such as Parkinson disease, Alzheimer disease, bipolar disorder,
      and cancer. However, it is unclear whether and how mtDNA polymorphisms affect
      intracellular function, such as calcium signaling or pH regulation. Here we
      searched for mtDNA polymorphisms that have intracellular functional significance
      using transmitochondrial hybrid cells (cybrids) carrying ratiometric Pericam
      (RP), a fluorescent calcium indicator, targeted to the mitochondria and nucleus.
      By analyzing the entire mtDNA sequence in 35 cybrid lines, we found that two
      closely linked nonsynonymous polymorphisms, 8701A and 10398A, increased the basal
      fluorescence ratio of mitochondria-targeted RP. Mitochondrial matrix pH was lower
      in the cybrids with 8701A/10398A than it was in those with 8701G/10398G,
      suggesting that the difference observed by RP was mainly caused by alterations in
      mitochondrial calcium levels. Cytosolic calcium response to histamine also tended
      to be higher in the cybrids with 8701A/10398A. It has previously been reported
      that 10398A is associated with an increased risk of Parkinson disease, Alzheimer
      disease, bipolar disorder, and cancer, whereas 10398G associates with longevity.
      Our findings suggest that these mtDNA polymorphisms may play a role in the
      pathophysiology of these complex diseases by affecting mitochondrial matrix pH
      and intracellular calcium dynamics.

PMID- 16895437
TI  - Family-based versus unrelated case-control designs for genetic associations.
AB  - The most simple and commonly used approach for genetic associations is the case
      control study design of unrelated people. This design is susceptible to
      population stratification. This problem is obviated in family-based studies, but
      it is usually difficult to accumulate large enough samples of well-characterized
      families. We addressed empirically whether the two designs give similar estimates
      of association in 93 investigations where both unrelated case-control and family
      based designs had been employed. Estimated odds ratios differed beyond chance
      between the two designs in only four instances (4%). The summary relative odds
      ratio (ROR) (the ratio of odds ratios obtained from unrelated case-control and
      family-based studies) was close to unity (0.96 [95% confidence interval, 0.91
      1.01]). There was no heterogeneity in the ROR across studies (amount of
      heterogeneity beyond chance I(2) = 0%). Differences on whether results were
      nominally statistically significant (p < 0.05) or not with the two designs were
      common (opposite classification rates 14% and 17%); this reflected largely
      differences in power. Conclusions were largely similar in diverse subgroup
      analyses. Unrelated case-control and family-based designs give overall similar
      estimates of association. We cannot rule out rare large biases or common small
      biases.

PMID- 16895438
TI  - Progress in charge transfer systems utilizing porphyrin donors and simple
      aromatic diimide acceptor units.
AB  - An overview of the evolution of artificial photosynthetic charge transfer systems
      containing porphyrin donors and pyromellitic or naphthalene diimide acceptor
      units is presented. Progression in this area of research is highlighted by the
      complexity of the systems, the nature of the medium separating donor and acceptor
      as well as the progression in the lifetime of the charge-separated state upon
      photoexcitation. A number of supramolecular systems that utilize hydrogen bonding
      or axial ligation of zinc porphyrins as a means for spatial orientation are
      highlighted.

PMID- 16895439
TI  - Repression of smoothened by patched-dependent (pro-)vitamin D3 secretion.
AB  - The developmentally important hedgehog (Hh) pathway is activated by binding of Hh
      to patched (Ptch1), releasing smoothened (Smo) and the downstream transcription
      factor glioma associated (Gli) from inhibition. The mechanism behind Ptch1
      dependent Smo inhibition remains unresolved. We now show that by mixing Ptch1
      transfected and Ptch1 small interfering RNA-transfected cells with Gli reporter
      cells, Ptch1 is capable of non-cell autonomous repression of Smo. The magnitude
      of this non-cell autonomous repression of Smo activity was comparable to the
      fusion of Ptch1-transfected cell lines and Gli reporter cell lines, suggesting
      that it is the predominant mode of action. CHOD-PAP analysis of medium
      conditioned by Ptch1-transfected cells showed an elevated 3beta-hydroxysteroid
      content, which we hypothesized to mediate the Smo inhibition. Indeed, the
      inhibition of 3beta-hydroxysteroid synthesis impaired Ptch1 action on Smo,
      whereas adding the 3beta-hydroxysteroid (pro-)vitamin D3 to the medium
      effectively inhibited Gli activity. Vitamin D3 bound to Smo with high affinity in
      a cyclopamine-sensitive manner. Treating zebrafish embryos with vitamin D3
      mimicked the smo(-/-) phenotype, confirming the inhibitory action in vivo. Hh
      activates its signalling cascade by inhibiting Ptch1-dependent secretion of the
      3beta-hydroxysteroid (pro-)vitamin D3. This action not only explains the
      seemingly contradictory cause of Smith-Lemli-Opitz syndrome (SLOS), but also
      establishes Hh as a unique morphogen, because binding of Hh on one cell is
      capable of activating Hh-dependent signalling cascades on other cells.

PMID- 16895442
TI  - Biodiversity loss threatens human well-being.

PMID- 16895440
TI  - An early role for WNT signaling in specifying neural patterns of Cdx and Hox gene
      expression and motor neuron subtype identity.
AB  - The link between extrinsic signaling, progenitor cell specification and neuronal
      subtype identity is central to the developmental organization of the vertebrate
      central nervous system. In the hindbrain and spinal cord, distinctions in the
      rostrocaudal identity of progenitor cells are associated with the generation of
      different motor neuron subtypes. Two fundamental classes of motor neurons, those
      with dorsal (dMN) and ventral (vMN) exit points, are generated over largely non
      overlapping rostrocaudal domains of the caudal neural tube. Cdx and Hox genes are
      important determinants of the rostrocaudal identity of neural progenitor cells,
      but the link between early patterning signals, neural Cdx and Hox gene
      expression, and the generation of dMN and vMN subtypes, is unclear. Using an in
      vitro assay of neural differentiation, we provide evidence that an early Wnt
      based program is required to interact with a later retinoic acid- and fibroblast
      growth factor-mediated mechanism to generate a pattern of Cdx and Hox profiles
      characteristic of hindbrain and spinal cord progenitor cells that prefigure the
      generation of vMNs and dMNs.

PMID- 16895441
TI  - Tomosyn inhibits synaptic vesicle priming in Caenorhabditis elegans.
AB  - Caenorhabditis elegans TOM-1 is orthologous to vertebrate tomosyn, a cytosolic
      syntaxin-binding protein implicated in the modulation of both constitutive and
      regulated exocytosis. To investigate how TOM-1 regulates exocytosis of synaptic
      vesicles in vivo, we analyzed C. elegans tom-1 mutants. Our electrophysiological
      analysis indicates that evoked postsynaptic responses at tom-1 mutant synapses
      are prolonged leading to a two-fold increase in total charge transfer. The
      enhanced response in tom-1 mutants is not associated with any detectable changes
      in postsynaptic response kinetics, neuronal outgrowth, or synaptogenesis.
      However, at the ultrastructural level, we observe a concomitant increase in the
      number of plasma membrane-contacting vesicles in tom-1 mutant synapses, a
      phenotype reversed by neuronal expression of TOM-1. Priming defective unc-13
      mutants show a dramatic reduction in plasma membrane-contacting vesicles,
      suggesting these vesicles largely represent the primed vesicle pool at the C.
      elegans neuromuscular junction. Consistent with this conclusion, hyperosmotic
      responses in tom-1 mutants are enhanced, indicating the primed vesicle pool is
      enhanced. Furthermore, the synaptic defects of unc-13 mutants are partially
      suppressed in tom-1 unc-13 double mutants. These data indicate that in the intact
      nervous system, TOM-1 negatively regulates synaptic vesicle priming.

PMID- 16895443
TI  - Beyond neutrality--ecology finds its niche.

PMID- 16895444
TI  - Amassing efforts against alien invasive species in Europe.

PMID- 16895446
TI  - New prospects for research on manipulation of insect vectors by pathogens.

PMID- 16895445
TI  - Roles of the host oxidative immune response and bacterial antioxidant
      rubrerythrin during Porphyromonas gingivalis infection.
AB  - The efficient clearance of microbes by neutrophils requires the concerted action
      of reactive oxygen species and microbicidal components within leukocyte secretory
      granules. Rubrerythrin (Rbr) is a nonheme iron protein that protects many air
      sensitive bacteria against oxidative stress. Using oxidative burst-knockout
      (NADPH oxidase-null) mice and an rbr gene knockout bacterial strain, we
      investigated the interplay between the phagocytic oxidative burst of the host and
      the oxidative stress response of the anaerobic periodontal pathogen Porphyromonas
      gingivalis. Rbr ensured the proliferation of P. gingivalis in mice that possessed
      a fully functional oxidative burst response, but not in NADPH oxidase-null mice.
      Furthermore, the in vivo protection afforded by Rbr was not associated with the
      oxidative burst responses of isolated neutrophils in vitro. Although the
      phagocyte-derived oxidative burst response was largely ineffective against P.
      gingivalis infection, the corresponding oxidative response to the Rbr-positive
      microbe contributed to host-induced pathology via potent mobilization and
      systemic activation of neutrophils. It appeared that Rbr also provided protection
      against reactive nitrogen species, thereby ensuring the survival of P. gingivalis
      in the infected host. The presence of the rbr gene in P. gingivalis also led to
      greater oral bone loss upon infection. Collectively, these results indicate that
      the host oxidative burst paradoxically enhances the survival of P. gingivalis by
      exacerbating local and systemic inflammation, thereby contributing to the
      morbidity and mortality associated with infection.

PMID- 16895447
TI  - Possible ancestral structure in human populations.
AB  - Determining the evolutionary relationships between fossil hominid groups such as
      Neanderthals and modern humans has been a question of enduring interest in human
      evolutionary genetics. Here we present a new method for addressing whether
      archaic human groups contributed to the modern gene pool (called ancient
      admixture), using the patterns of variation in contemporary human populations.
      Our method improves on previous work by explicitly accounting for recent
      population history before performing the analyses. Using sequence data from the
      Environmental Genome Project, we find strong evidence for ancient admixture in
      both a European and a West African population (p approximately 10(-7)), with
      contributions to the modern gene pool of at least 5%. While Neanderthals form an
      obvious archaic source population candidate in Europe, there is not yet a clear
      source population candidate in West Africa.

PMID- 16895448
TI  - Matrix-assisted laser desorption/ionisation, time-of-flight mass spectrometry in
      genomics research.
AB  - The beginning of this millennium has seen dramatic advances in genomic research.
      Milestones such as the complete sequencing of the human genome and of many other
      species were achieved and complemented by the systematic discovery of variation
      at the single nucleotide (SNP) and whole segment (copy number polymorphism)
      level. Currently most genomics research efforts are concentrated on the
      production of whole genome functional annotations, as well as on mapping the
      epigenome by identifying the methylation status of CpGs, mainly in CpG islands,
      in different tissues. These recent advances have a major impact on the way
      genetic research is conducted and have accelerated the discovery of genetic
      factors contributing to disease. Technology was the critical driving force behind
      genomics projects: both the combination of Sanger sequencing with high-throughput
      capillary electrophoresis and the rapid advances in microarray technologies were
      keys to success. MALDI-TOF MS-based genome analysis represents a relative
      newcomer in this field. Can it establish itself as a long-term contributor to
      genetics research, or is it only suitable for niche areas and for laboratories
      with a passion for mass spectrometry? In this review, we will highlight the
      potential of MALDI-TOF MS-based tools for resequencing and for epigenetics
      research applications, as well as for classical complex genetic studies, allele
      quantification, and quantitative gene expression analysis. We will also identify
      the current limitations of this approach and attempt to place it in the context
      of other genome analysis technologies.

PMID- 16895451
TI  - Motion aftereffect elicits smooth pursuit eye movements.
AB  - A moving stimulus is normally required to elicit smooth pursuit eye movements
      that serve to keep the retinal image of moving objects on the fovea. Recent
      experiments have shown that in cases where motion cues are ambiguous, pursuit eye
      movements tend to agree in direction and speed with the percept of motion. Here,
      we exploit the motion aftereffect (MAE) to show for the first time that smooth
      pursuit eye movements can also be elicited by the illusory motion of a stationary
      stimulus. After prolonged exposure to a moving stimulus, subjects show reliable
      pursuit of a physically stationary stimulus that is perceived to be moving.
      Conversely, the eyes remain stationary when viewing a physically moving stimulus
      that is perceived to be stationary. The MAE biases smooth eye movements in a way
      that agrees with the constant offset that is required to null the MAE
      perceptually. The agreement between perception and pursuit holds over a variety
      of stimulus conditions that modulate the magnitude of the MAE.

PMID- 16895449
TI  - Haplotype block structure is conserved across mammals.
AB  - Genetic variation in genomes is organized in haplotype blocks, and species
      specific block structure is defined by differential contribution of population
      history effects in combination with mutation and recombination events. Haplotype
      maps characterize the common patterns of linkage disequilibrium in populations
      and have important applications in the design and interpretation of genetic
      experiments. Although evolutionary processes are known to drive the selection of
      individual polymorphisms, their effect on haplotype block structure dynamics has
      not been shown. Here, we present a high-resolution haplotype map for a 5-megabase
      genomic region in the rat and compare it with the orthologous human and mouse
      segments. Although the size and fine structure of haplotype blocks are species
      dependent, there is a significant interspecies overlap in structure and a
      tendency for blocks to encompass complete genes. Extending these findings to the
      complete human genome using haplotype map phase I data reveals that linkage
      disequilibrium values are significantly higher for equally spaced positions in
      genic regions, including promoters, as compared to intergenic regions, indicating
      that a selective mechanism exists to maintain combinations of alleles within
      potentially interacting coding and regulatory regions. Although this
      characteristic may complicate the identification of causal polymorphisms
      underlying phenotypic traits, conservation of haplotype structure may be employed
      for the identification and characterization of functionally important genomic
      regions.

PMID- 16895452
TI  - The swinging doors of perception: stereomotion without binocular matching.
AB  - Until recently, it was considered necessary for features in the two eyes to be
      matched before the evaluation of differences in their locations (binocular
      disparities) could reveal depth information. Motion in depth can also be
      perceived binocularly from related changes in the locations of matched binocular
      features. However, unmatched features can arise when a binocular object occludes
      more distant features in one eye but not the other. The presence and extent of
      such features can provide quantitative depth information, although perceived
      depth relative to geometrical predictions may vary from one such arrangement to
      another. The ability of humans to perceive motion in depth from unmatched stimuli
      has not previously been explored. Here, we use B. Gillam, S. Blackburn, and K.
      Nakayama's (1999) "monocular gap" stimuli to investigate perception of motion in
      depth simulated by a change in the extent of a monocularly occluded feature in a
      binocular display. Settings of a motion in depth probe revealed that the
      magnitude of perceived motion in depth is generally as large as that for a
      stimulus containing matchable binocular features. We show that our stimuli
      provide disambiguating information not present in similar static stimuli. We
      conclude that in the computation of motion in depth, a binocular match is not
      required. A new cue-dynamic half-occlusion-can be used to reach an accurate
      percept.

PMID- 16895450
TI  - Anatomic demarcation by positional variation in fibroblast gene expression
      programs.
AB  - Fibroblasts are ubiquitous mesenchymal cells with many vital functions during
      development, tissue repair, and disease. Fibroblasts from different anatomic
      sites have distinct and characteristic gene expression patterns, but the
      principles that govern their molecular specialization are poorly understood.
      Spatial organization of cellular differentiation may be achieved by unique
      specification of each cell type; alternatively, organization may arise by cells
      interpreting their position along a coordinate system. Here we test these models
      by analyzing the genome-wide gene expression profiles of primary fibroblast
      populations from 43 unique anatomical sites spanning the human body. Large-scale
      differences in the gene expression programs were related to three anatomic
      divisions: anterior-posterior (rostral-caudal), proximal-distal, and dermal
      versus nondermal. A set of 337 genes that varied according to these positional
      divisions was able to group all 47 samples by their anatomic sites of origin.
      Genes involved in pattern formation, cell-cell signaling, and matrix remodeling
      were enriched among this minimal set of positional identifier genes. Many
      important features of the embryonic pattern of HOX gene expression were retained
      in fibroblasts and were confirmed both in vitro and in vivo. Together, these
      findings suggest that site-specific variations in fibroblast gene expression
      programs are not idiosyncratic but rather are systematically related to their
      positional identities relative to major anatomic axes.

PMID- 16895453
TI  - Discrimination of amplitude spectrum slope in the fovea and parafovea and the
      local amplitude distributions of natural scene imagery.
AB  - A number of studies have investigated whether human visual performance can be
      related to the general form of the amplitude spectra (i.e., 1/f(alpha)) of
      natural scenes. Here, it is argued that there are some discrepancies in the data
      between some of those studies and that one possible explanation for the
      discrepancies may be related to differences in methodology (e.g., stimuli
      presented to the fovea as opposed to the parafovea). We sought to resolve some of
      the discrepancies with two psychophysical paradigms involving alpha
      discrimination with visual noise and natural scene image patches presented to the
      fovea or parafovea. Fovea-parafovea threshold differences were apparent for
      stimuli possessing alpha values < 1.0, with the parafovea typically showing
      highest thresholds for reference alpha values in the 0.74-0.85 range. Both fovea
      and parafovea thresholds were lowest in the 1.2-1.4 range. In addition, we
      conducted a local amplitude distribution analysis (i.e., assessed local alpha)
      with a large set of high-resolution natural scene imagery and found that the
      results of that analysis provided a better account of the alpha discrimination
      thresholds for stimuli presented to the fovea as opposed to the parafovea.

PMID- 16895454
TI  - The influence of biological motion perception on structure-from-motion
      interpretations at different speeds.
AB  - Nonrigid point-light representations of biological motion are ideal to test
      higher level influences on structure-from-motion (SFM) perception. Here, we
      investigated the influence of biological motion perception on 3D SFM
      interpretations at different speeds. We presented nonrigid biological motion and
      rigid structures rotating around the vertical axis. The familiarity of the
      stimuli was changed by presenting three walker types: normal, inverted, and phase
      scrambled. Subjects had to discriminate rotation in depth and rigidity. We found
      that at lower-than-natural gait speeds, subjects perceived nonrigid biological
      motion to be rotating in depth, especially when the walker type was less
      familiar. In contrast, the percept of rigidity was correct at all speeds. A
      second experiment, in which a constant fraction of the gait cycle was presented,
      confirmed the influence of speed and additionally showed that brief displays of a
      familiar form at a high speed facilitate biological motion interpretations. The
      more veridical percept of rotation toward higher speeds fits the idea of
      biological motion channels tuned to higher-more natural walking-speeds that
      overrule a default assumption to perceive trajectories in depth. We also
      speculate that the rotation-in-depth percept at lower speeds points toward the
      existence of low-speed-tuned object motion channels.

PMID- 16895455
TI  - The influence of the Brentano illusion on eye and hand movements.
AB  - When making an eye movement and a hand movement toward a visual target, the
      movements could be guided by visual judgments of direction and distance (or
      length) of the required displacement (vector coding), estimates of the final
      position (position coding), or both. Using the same information for the eyes and
      the hand is efficient; however, if this information contains an error, this
      causes both the eye and the hand to be incorrect. In this study, we tried to find
      out whether saccades and pointing movements use the same source of information
      when eye and hand movements are performed either concurrently or separately. Four
      experiments have been performed using the Brentano illusion, which primarily
      influences judgments of length but not those of position. This illusion only
      influences movements if the illusory length is relevant for the task,
      demonstrating that vector coding is involved. Subjects made saccades, pointing
      movements, or both between vertices of the Brentano illusion. The illusion
      influenced saccades and pointing movements when these movements were performed
      concurrently and separately, showing that the eye and the hand use vector coding.
      However, depending on the task, eye and hand movements were influenced to a
      different extent. This favors the interpretation that the eyes and the hand use a
      common motor command but each with a different relative contribution of vector
      coding.

PMID- 16895456
TI  - Adaptation to sine-wave gratings selectively reduces the contrast gain of the
      adapted stimuli.
AB  - Adapting to sinusoidal gratings selectively reduces contrast sensitivity to
      subsequent test stimuli. To investigate the perceptual processes underlying
      selective adaptation, we developed an external noise plus adaptation paradigm and
      a theoretical framework based on a noisy observer model (the contrast-gain
      control Perceptual Template Model [cgcPTM]). After adapting to a 45 deg, 2-Hz
      counter-flickering sine grating of 0.8 contrast, observers performed two-interval
      forced-choice detection of Gabors of matched spatial frequency, tilted at either
      45 or 135 deg and embedded in one of six levels of white external noise
      (Experiment 1) or embedded in orientation band-pass-filtered external noise
      (Experiment 2). On the basis of the cgcPTM, we found that adaptation selectively
      reduced the contrast gain of the perceptual template at the adapted spatial
      frequency and orientation without altering either pre- or post-gain-control
      (additive and multiplicative) noises or changing transducer nonlinearity. Modeled
      as notches on the perceptual templates, the estimated full orientation bandwidth
      of adaptation at half height was about 8.3 deg.

PMID- 16895457
TI  - Combining achromatic and chromatic cues to transparency.
AB  - We investigated how achromatic and chromatic cues interact to produce
      transparency. Observers were shown six-region stimulus displays similar to those
      used by R. Kasrai and F. A. A. Kingdom (2001) and made adjustments of the color
      and luminance attributes of one of the filter regions to achieve the best percept
      of transparency. The dependent measure of primary interest was setting
      reliability, the reciprocal of setting variance. We wished to determine whether
      the combination of chromatic and achromatic information leads to enhanced
      reliability of perceived transparency. In Experiment 1, we measured reliability
      for achromatic, L, superimposed luminance with color, L + C, and superimposed
      luminance with polarity-reversing color, L + iC. We found that observers'
      reliability was highest for the L + C condition, consistent with effective cue
      combination. In a second experiment, we compared setting reliability for L, L +
      C, and a new chromatic-only condition C. In the L + C condition, observers were
      asked to make separate and iterative settings of luminance and color to achieve
      the best percept of transparency. We compared their settings in L with the
      luminance settings in L + C and their settings in C with their color settings in
      L + C. Color adjustments were more reliable when accompanied by luminance
      information but not vice versa. In Experiment 3, we manipulated the transmittance
      of the achromatic and chromatic filters separately and investigated how this
      influences the settings made for each attribute. No systematic influence of
      filter transmittance on the settings made for perceived transparency was found.

PMID- 16895458
TI  - The interaction of eye movements and retinal signals during the perception of 3-D
      motion direction.
AB  - When an object is tracked with the eyes, veridical perception of the motion of
      that object and other objects requires the brain to take account of and
      compensate for the eye movement. Here, I explore the effects of version and
      vergence eye movements on three-dimensional (3-D) motion perception. After
      demonstrating that eye movement compensation can be poor for detecting small
      objects moving in depth, I develop two models for how eye movement and visual
      signals may interact during the perception of 3-D motion direction. The first
      model assumes that the visual system is aiming to form an explicit representation
      of 3-D motion. From the results of a second experiment, on 3-D motion direction
      judgements, I show that this model could only hold with almost perfect 3-D motion
      compensation, contradicting the results from the first experiment. A second model
      assumes a much simpler strategy for estimating 3-D motion direction, based on
      recent experimental work. It predicts that compensation for vergence is not
      required because the Z-component of 3-D motion is not needed for direction
      judgements, consistent with the experimental results. This suggests that, for 3-D
      motion direction discrimination and angle judgements, extraretinal signals from
      vergence are not used.

PMID- 16895459
TI  - Learning to discriminate complex movements: biological versus artificial
      trajectories.
AB  - The recognition of complex body movements and actions is a fundamental visual
      capacity very important for social communication. It seems possible that movement
      recognition is based on a general capability of the visual system to learn
      complex visual motion patterns. Alternatively, this visual function might exploit
      specialized mechanisms for the analysis of biologically relevant movements, for
      example, of humans or animals. To investigate this question, we trained human
      observers to discriminate novel motion patterns that were generated, exploiting a
      new technique for stimulus generation by motion morphing. We tested the learning
      of different classes of novel movement stimuli. One group of stimuli was fully
      consistent with human movements. A second class of stimuli was based on
      artificial skeleton models that were inconsistent with human and animal bodies. A
      third group of stimuli specified the same local motion information as human
      movements but was inconsistent with an underlying articulated shape. Participants
      learned both classes of articulated movements very fast in an orientation
      dependent manner. Learning speed and accuracy were strikingly similar and
      independent of the similarity of the stimuli with biologically relevant body
      shapes. For the class of stimuli without underlying articulated shape, however,
      we did not observe significant improvements of the discrimination performance
      after training. Our results indicate the existence of a fast visual learning
      process for complex articulated movement patterns, which likely is relevant for
      biological motion perception. This process seems to operate independently of the
      consistency of the patterns with biologically relevant body shapes but seems to
      require the compatibility of the learned movements with a global underlying
      shape.

PMID- 16895460
TI  - Perceived orientation of complex shape reflects graded part decomposition.
AB  - Although the orientation of line segments and simple shapes is a well-studied
      area of vision, little is known about geometric factors that influence perceived
      orientation of complex multipart shapes. The study of these factors is of
      interest because it allows for an insight into the basic problem of how local
      geometric attributes are integrated perceptually into a global shape
      representation. We examined the perceived orientation of two-part shapes using an
      adjustment method and a 2AFC task. In particular, we investigated the influence
      of the perceptual salience, or distinctiveness, of a part--as defined by the
      turning angles at its boundaries--and its area relative to the main "base" part.
      In contrast to previous results on simple shapes, our results exhibited large and
      systematic deviations of perceived orientation from the principal axis of the
      shape. For shapes with sharp part boundaries, perceived global orientation
      deviated maximally from the principal axis and was approximated by the axis of
      the main base part of the shape. With weakening part boundaries, the perceived
      orientation gradually approached the principal axis of the entire shape,
      reflecting that both parts were taken into account in estimating orientation. The
      results are consistent with a differentially weighted principal-axis computation
      in which the attached part is given systematically lower weighting with
      increasing turning angles at the part boundaries. They thus allow a quantitative
      characterization of part salience in terms of part independence: Turning angles
      at a part's boundaries determine the extent to which its influence is
      perceptually separable from the rest of the shape. We suggest that Robust
      Statistics may provide a useful framework for quantifying the influence of part
      segmentation on visual estimation.

PMID- 16895461
TI  - Changes in expectation consequent on experience, modeled by a simple, forgetful
      neural circuit.
AB  - Our expectation of an event such as a visual stimulus clearly depends on previous
      experience, but how the brain computes this expectation is currently not fully
      understood. Because expectation influences the time to respond to a stimulus, we
      arranged for the probability of a visual target to suddenly change and found that
      the time taken to make an eye movement to it then changed continuously,
      eventually stabilizing at a level reflecting the new probability. The time course
      of this change can be modeled making a simple assumption: that the brain
      discounts old information about the probability of an event by a factor lambda,
      relative to new information. The value of lambda presumably represents a
      compromise between responding rapidly to genuine changes in the environment and
      not prematurely discarding information still of value. The model we propose may
      be implemented by a very simple neural circuit composed of only a few neurons.

PMID- 16895462
TI  - Visual perception of biological motion by form: a template-matching analysis.
AB  - Biological motion perception is referred to as the ability to recognize a moving
      human figure from no more than a few moving point lights. Such point-light
      stimuli contain limited form information about the shape of the body and local
      image motion signals from the moving points. The contributions of form and motion
      to the vivid perception of point-light displays are subject to controversy in the
      discussion. While some studies claim that local motion signals are critical,
      others emphasize the role of global form cues. Here, we present a template
      matching approach to investigate the role of global form analysis. We used a
      template-matching method that derives biological motion exclusively from form
      information. The algorithm used static postures monitored from walking humans as
      stored templates. We compared the simulation results to psychophysical
      experiments with the commonly used point-light walker and a variant point-light
      walker with near-absent local motion signals. The common result in all
      experiments was a high correlation between simulation results and psychophysical
      data. The results show that the limited form information in point-light stimuli
      might be sufficient to perceive biological motion. We suggest that it is possible
      for humans to extract the sparse form information in point-light walkers and to
      use it to perceive biological motion by integrating dynamic form information over
      time.

PMID- 16895463
TI  - Adaptation aftereffects in the perception of gender from biological motion.
AB  - Human visual perception is highly adaptive. While this has been known and studied
      for a long time in domains such as color vision, motion perception, or the
      processing of spatial frequency, a number of more recent studies have shown that
      adaptation and adaptation aftereffects also occur in high-level visual domains
      like shape perception and face recognition. Here, we present data that
      demonstrate a pronounced aftereffect in response to adaptation to the perceived
      gender of biological motion point-light walkers. A walker that is perceived to be
      ambiguous in gender under neutral adaptation appears to be male after adaptation
      with an exaggerated female walker and female after adaptation with an exaggerated
      male walker. We discuss this adaptation aftereffect as a tool to characterize and
      probe the mechanisms underlying biological motion perception.

PMID- 16895465
TI  - Mechanisms of cyclic-di-GMP signaling in bacteria.
AB  - Cyclic-di-GMP is a ubiquitous second messenger in bacteria. The recent discovery
      that c-di-GMP antagonistically controls motility and virulence of single,
      planktonic cells on one hand and cell adhesion and persistence of multicellular
      communities on the other has spurred interest in this regulatory compound.
      Cellular levels of c-di-GMP are controlled through the opposing activities of
      diguanylate cyclases and phosphodiesterases, which represent two large families
      of output domains found in bacterial one- and two-component systems. This review
      concentrates on structural and functional aspects of diguanylate cyclases and
      phosphodiesterases, and on their role in transmitting environmental stimuli into
      a range of different cellular functions. In addition, we examine several well
      established model systems for c-di-GMP signaling, including Pseudomonas, Vibrio,
      Caulobacter, and Salmonella.

PMID- 16895466
TI  - DNA double-strand break repair: all's well that ends well.
AB  - Breaks in both DNA strands are a particularly dangerous threat to genome
      stability. At a DNA double-strand break (DSB), potentially lost sequence
      information cannot be recovered from the same DNA molecule. However, simple
      repair by joining two broken ends, though inherently error prone, is preferable
      to leaving ends broken and capable of causing genome rearrangements. To avoid DSB
      induced genetic disinformation and disruption of vital processes, such as
      replication and transcription, cells possess robust mechanisms to repair DSBs.
      Because all breaks are not created equal, the particular repair mechanism used
      depends largely on what is possible and needed based on the structure of the
      broken DNA. We argue that although categorizing different DSB repair mechanisms
      along pathways and subpathways can be conceptually useful, in cells flexible and
      reversible interactions among DSB repair factors form a web from which a
      nonpredetermined path to repair for any number of different DNA breaks will
      emerge.

PMID- 16895469
TI  - Caspase-containing complexes in the regulation of cell death and inflammation.
AB  - Caspases are a family of cysteine proteases that are essential in the initiation
      and execution of apoptosis and the proteolytic maturation of inflammatory
      cytokines such as IL-1beta and IL-18. Caspases can be subdivided into those that
      have a large prodomain and those that have not. In general, apoptotic and
      inflammatory signalling pathways are initiated when large-prodomain caspases are
      recruited to large protein complexes via homotypic interactions involving death
      domain folds. The formation of these specialised multimeric platforms involves
      three major functions: (1) the sensing of cellular stress, damage, infection or
      inflammation; (2) multimerisation of the platform; and (3) recruitment and
      conformational activation of caspases. In this overview we discuss the complexes
      implicated in the regulation of cell death and inflammatory processes such as the
      death-inducing signalling complex (DISC), the apoptosome, the inflammasomes and
      the PIDDosome. We describe their sensing functions, compositions and functional
      outcomes. Inhibitory protein families such as FLIPs and CARD-only proteins
      prevent the recruitment of caspases in these sensing complexes, avoiding
      inappropriate initiation of cell death or inflammation.

PMID- 16895470
TI  - Regulation of human cathepsin B by alternative mRNA splicing: homeostasis, fatal
      errors and cell death.
AB  - One of the control mechanisms of cathepsin B biosynthesis and trafficking
      operates through alternative splicing of pre-mRNA. An mRNA lacking exon 2 is more
      efficiently translated than that containing all exons, and may be responsible for
      elevated biosynthesis and enzyme routing to the extracellular space, with
      critical consequences for connective tissue integrity in pathologies such as
      cancer and arthritis. mRNA missing exons 2 and 3 encodes a truncated procathepsin
      B form that is targeted to mitochondria. This enzyme variant is catalytically
      inactive because it cannot properly fold. However, it provokes a cascade of
      events, which result first in morphological changes in intracellular organelles
      and the nucleus, finally leading to cell death.

PMID- 16895472
TI  - C. elegans as a model system to study the function of the COG complex in animal
      development.
AB  - The conserved oligomeric Golgi (COG) complex is an octameric protein complex
      associated with the Golgi apparatus and is required for proper sorting and
      glycosylation of Golgi resident enzymes and secreted proteins. Although COG
      complex function has been extensively studied at the cellular and subcellular
      levels, its role in animal development mostly remains unknown. Recently,
      mutations in the components of the COG complex were found to cause abnormal gonad
      morphogenesis in Caenorhabditis elegans. In C. elegans, the COG complex acts in
      the glycosylation of an ADAM (a disintegrin and metalloprotease) family protein,
      MIG-17, which directs migration of gonadal distal tip cells to lead gonad
      morphogenesis. This is the first link between the COG complex and the function of
      an ADAM protease that is directly involved in organ morphogenesis, demonstrating
      the potential of C. elegans as a model system to study COG function in animal
      development.

PMID- 16895471
TI  - The peptidases from fungi and viruses.
AB  - Fungi and viruses encode a variety of peptidases having a plethora of functions.
      Many fungal peptidases are extracellular and are likely used to degrade proteins
      in their environment. Viral peptidases are processing enzymes, intimately
      involved in the virus infectious cycle. The viral RNA genome is translated by the
      host-cell machinery into a large polyprotein that is cleaved by the viral
      peptidases into mature capsid proteins, non-structural proteins and enzymes. I
      review the structure and catalytic mechanism of scytalidoglutamic peptidase
      isolated from the wood-destroying fungus Scytalidium lignicolum. This enzyme has
      a unique beta-sandwich fold and a novel catalytic mechanism based on a glutamate,
      a glutamine and a nucleophilic water molecule. Hepatitis A virus (HAV) 3C
      peptidase was the first structure identified for a viral 3C enzyme that exhibited
      the three-dimensional fold of the chymotrypsin family of serine peptidases but
      had a cysteine sulfur atom instead of the serine oxygen as the nucleophile. The
      structure of HAV 3C was unusual in that the Asp residue expected as the third
      member of the catalytic triad did not interact with the general base His. The
      present structure is of a beta-lactone-inhibited version of HAV 3C that has a
      restored catalytic triad.

PMID- 16895473
TI  - Functional responses of bone cells to thrombin.
AB  - Cells responsible for the formation and maintenance of bone express thrombin
      responsive members of the protease-activated receptor family of G protein-coupled
      receptors. Thrombin has been shown to elicit a number of functional responses in
      these cells, including proliferation and cytokine production in osteoblasts.
      Many, but not all, of the effects of thrombin on bone cells are initiated by
      activation of protease-activated receptor-1. A combination of in vitro
      observations and results of in vivo studies in protease-activated receptor-1-null
      mice suggest that thrombin plays multiple roles in the early stages of bone
      healing.

PMID- 16895474
TI  - Homologous substitution of ACE C-domain regions with N-domain sequences: effect
      on processing, shedding, and catalytic properties.
AB  - Angiotensin-converting enzyme (ACE) exists as two isoforms: somatic ACE (sACE),
      comprised of two homologous N and C domains, and testis ACE (tACE), comprised of
      the C domain only. The N and C domains are both active, but show differences in
      substrate and inhibitor specificity. While both isoforms are shed from the cell
      surface via a sheddase-mediated cleavage, tACE is shed much more efficiently than
      sACE. To delineate the regions of tACE that are important in catalytic activity,
      intracellular processing, and regulated ectodomain shedding, regions of the tACE
      sequence were replaced with the corresponding N-domain sequence. The resultant
      chimeras C1-163Ndom-ACE, C417-579Ndom-ACE, and C583-623Ndom-ACE were processed to
      the cell surface of transfected Chinese hamster ovary (CHO) cells, and were
      cleaved at the identical site as that of tACE. They also showed acquisition of N
      domain-like catalytic properties. Homology modelling of the chimeric proteins
      revealed structural changes in regions required for tACE-specific catalytic
      activity. In contrast, C164-416Ndom-ACE and C191-214Ndom-ACE demonstrated
      defective intracellular processing and were neither enzymatically active nor
      shed. Therefore, critical elements within region D164-V416 and more specifically
      I191-T214 are required for the processing, cell-surface targeting, and enzyme
      activity of tACE, and cannot be substituted for by the homologous N-domain
      sequence.

PMID- 16895475
TI  - Production and processing of a recombinant Fasciola hepatica cathepsin B-like
      enzyme (FhcatB1) reveals potential processing mechanisms in the parasite.
AB  - The liver fluke, Fasciola hepatica, apparently uses a number of cysteine
      proteases during its life cycle, most likely for feeding, immune evasion and
      invasion of tissues. A cathepsin B-like enzyme (herein referred to as FhcatB1)
      appears to be a major enzyme secreted by the invasive, newly excysted juvenile
      flukes of this parasite. To examine the processing mechanisms for this enzyme, a
      recombinant form was expressed in Pichia pastoris and purified to yield a
      homogenous pool of the enzyme. The purified enzyme could be autoactivated at low
      pH via a bi-molecular mechanism, a process that was greatly accelerated by the
      presence of large, negatively charged molecules such as dextran sulfate. The
      enzyme could also apparently be processed to the correct size by an asparaginyl
      endopeptidase via cleavage in an unusual insertion N-terminal to the normal
      cleavage site used to yield the active form of the enzyme. Thus, there appear to
      be a number of ways in which this enzyme can be processed to its optimally active
      form prior to secretion by F. hepatica.

PMID- 16895477
TI  - Single-cell resolution imaging of membrane-anchored hepatitis C virus NS3/4A
      protease activity.
AB  - The study of host and viral membrane-associated proteases has been hampered due
      to a lack of in vivo assays. We report here the development of a cell-based
      fluorescence assay for detecting hepatitis C virus (HCV) NS3/4A juxtamembrane
      protease activity. Intracellular membrane-anchored protein substrates were
      engineered comprising: (1) an endoplasmic reticulum targeting domain, the HCV
      NS5A N-terminal amphipathic alpha-helix; (2) a NS3/4A-specific cleavage site; and
      (3) a red fluorescent reporter group, DsRed. The results of our
      immunofluorescence and Western blotting studies demonstrate that our membrane
      bound fluorescent probe was cleaved specifically and efficiently by NS3/4A
      expressed in human cells.

PMID- 16895476
TI  - Development of a red-shifted fluorescence-based assay for SARS-coronavirus 3CL
      protease: identification of a novel class of anti-SARS agents from the tropical
      marine sponge Axinella corrugata.
AB  - SARS-coronavirus (SARS-CoV) encodes a main protease, 3CLpro, which plays an
      essential role in the viral life cycle and is currently the prime target for
      discovering new anti-coronavirus agents. In this article, we report our success
      in developing a novel red-shifted (RS) fluorescence-based assay for 3CLpro and
      its application for identifying small-molecule anti-SARS agents from marine
      organisms. We have synthesised and characterised the first generation of a red
      shifted internally quenched fluorogenic substrate (RS-IQFS) for 3CLpro based on
      resonance energy transfer between the donor and acceptor pair CAL Fluor Red 610
      and Black Hole Quencher-1 (Km and kcat values of 14 microM and 0.65 min-1). The
      RS-IQFS primary sequence was selected based on the results of our screening
      analysis of 3CLpro performed using a series of blue-shifted (BS)-IQFSs
      corresponding to the 3CLpro-mediated cleavage junctions of the SARS-CoV
      polyproteins. In contrast to BS-IQFSs, the RS-IQFS was not susceptible to
      fluorescence interference from coloured samples and allowed for successful
      screening of marine natural products and identification of a coumarin derivative,
      esculetin-4-carboxylic acid ethyl ester, a novel 3CLpro inhibitor (IC50=46
      microM) and anti-SARS agent (EC50=112 microM; median toxic concentration>800
      microM) from the tropical marine sponge Axinella corrugata.

PMID- 16895479
TI  - Proteolytic mechanism of a novel mitochondrial and chloroplastic PreP
      peptidasome.
AB  - The 2.1-A-resolution crystal structure of the novel mitochondrial and
      chloroplastic metalloendopeptidase, AtPreP1, revealed a unique peptidasome
      structure, in which the two halves of the enzyme completely enfold a huge
      proteolytic cavity. Based on the structure, we proposed a novel mechanism for
      proteolysis involving hinge-bending motions, which cause the protease to open and
      close in response to substrate binding. We generated four double-mutants of
      AtPreP1 by introducing cysteines at positions where disulfide bonds can be formed
      in order to lock and unlock the protease and tested the activity under oxidizing
      and reducing conditions. The overall results support the proposed mechanism.

PMID- 16895478
TI  - Treatment of MCF-7 cells with taxol and etoposide induces distinct alterations in
      the expression of apoptosis-related genes BCL2, BCL2L12, BAX, CASPASE-9 and FAS.
AB  - We studied alterations in the mRNA expression levels of BCL2 (Bcl-2), BCL2L12,
      BAX, FAS and CASPASE-9 genes in the MCF-7 breast cancer cell line in response to
      treatment with two anticancer drugs. Cell toxicity was evaluated by the MTT
      method, trypan blue staining and DNA laddering, whereas the expression levels of
      the apoptosis-related genes were analysed by RT-PCR using gene-specific primers.
      In the case of etoposide, down-regulation of the BCL2L12-A gene variant and of
      CASPASE-9, as well as upregulation of BAX, was observed, whereas treatment of MCF
      7 cells with taxol led to down-regulation of the mRNA levels of all genes
      examined. Our results support the idea that after long-term clinical studies,
      mRNA expression analysis of BCL2L12 and other members of the BCL2 gene family may
      serve as useful molecular markers predicting chemotherapy response in breast
      cancer.

PMID- 16895480
TI  - Tripeptidyl-peptidase I in health and disease.
AB  - The lysosomal lumen contains numerous acidic hydrolases involved in the
      degradation of carbohydrates, lipids, proteins, and nucleic acids, which are
      basic cell components that turn over continuously within the cell and/or are
      ingested from outside of the cell. Deficiency in almost any of these hydrolases
      causes accumulation of the undigested material in secondary lysosomes, which
      manifests itself as a form of lysosomal storage disorder (LSD). Mutations in
      tripeptidyl-peptidase I (TPP I) underlie the classic late-infantile form of
      neuronal ceroid lipofuscinoses (CLN2), the most common neurodegenerative
      disorders of childhood. TPP I is an aminopeptidase with minor endopeptidase
      activity and Ser475 serving as an active-site nucleophile. The enzyme is
      synthesized as a highly glycosylated precursor transported by mannose-6-phosphate
      receptors to lysosomes, where it undergoes proteolytic maturation. This review
      summarizes recent progress in understanding of TPP I biology and molecular
      pathology of the CLN2 disease process, including distribution of the enzyme, its
      biosynthesis, glycosylation, transport and activation, as well as catalytic
      mechanisms and their potential implications for pathogenesis and treatment of the
      underlying disease. Promising data from gene and stem cell therapy in laboratory
      animals raise hope that CLN2 will be the first neurodegenerative LSD for which
      causative treatment will become available for humans.

PMID- 16895481
TI  - Molecular and functional analysis of new members of the wheat PR4 gene family.
AB  - Five new genes belonging to the pathogenesis-related (PR) 4 family have been
      cloned and characterised in Triticum aestivum. Two full-length genes, named wPR4e
      and wPR4f-b, were isolated by library screening, demonstrating the presence of a
      small intron only in wPR4f-b. Two other PR4 genes (wPR4f-a and wPR4f-c) were
      isolated by PCR, showing very high sequence identity with wPR4f-b and
      constituting a new sub-family. Transcription start analysis was performed by RLM
      RACE, leading to the isolation of a fifth gene, named wPR4g, that is highly
      homologous to wPR4e; both encode putative vacuolar PR4 proteins (Wheatwin7 and
      Wheatwin5, respectively). wPR4e and wPR4f sub-family genes are induced by F.
      culmorum infection, by chemicals that lead to systemic acquired resistance and by
      wounding, showing different spatial and temporal induction pathways. In silico
      analysis of the 5' untranslated regions of wPR4e and wPR4f-b revealed the
      presence of several abiotic and biotic stress-responsive elements. wPR4e and
      wPR4f-b putative promoters were fused to the beta-glucuronidase (GUS) reporter
      gene, and transient and stable expression assays demonstrated that both are able
      to drive expression of GUS. Characterisation of these new PR4 genes and
      particularly of their 5' untranslated regions, as well as the determination of
      their expression patterns, will contribute to our understanding of the
      responsiveness of this gene family to various stress conditions and of its role
      in plant defence.

PMID- 16895482
TI  - C-Terminal truncations of syncytin-1 (ERVWE1 envelope) that increase its
      fusogenicity.
AB  - Syncytin-1, the envelope protein of ERVWE1, an endogenous retrovirus of the HERV
      W family, plays an important role in regulating fusion of the placental
      trophoblast. At least one of its receptors is expressed on a variety of human
      cell types. Its ability to fuse cells makes it an attractive candidate molecule
      in gene therapy against cancer. We studied the relevance of sequences in the
      cytoplasmic tail of syncytin-1 for inducing cell-cell fusion. We generated a
      series of C-terminally truncated syncytin-1 variants. Sequences immediately
      adjacent to the transmembrane region of syncytin-1 were necessary for inducing
      optimal fusion, whereas the extreme C-terminus of syncytin-1 partially inhibited
      its fusogenicity. Two variants of syncytin-1, truncated after residues 483 and
      515, were significantly hyperfusogenic compared to wild-type syncytin-1. Cellular
      and cell-surface expression levels of these two variant proteins were similar to
      those of wild-type syncytin-1. In testing the latter we found that only a very
      minor portion of recombinantly expressed cellular syncytin-1 was fully mature and
      expressed on the cell surface. Our results contribute to the understanding of the
      structure-function relationship of syncytin-1, and might have implications for
      the use of this molecule in gene therapy.

PMID- 16895483
TI  - Disease processes may be reflected by correlations among tissue kallikrein
      proteases but not with proteolytic factors uPA and PAI-1 in primary ovarian
      carcinoma.
AB  - In epithelial ovarian cancer, the high mortality rate is usually ascribed to late
      diagnosis, since these tumors commonly lack early-warning symptoms, but tumor
      associated biomarkers useful for prognosis or therapy response prediction are in
      short supply. However, members of the tissue kallikrein serine protease family,
      the serine protease uPA and its inhibitor PAI-1, are associated with tumor
      progression of ovarian cancer. Therefore, we used ELISA to determine uPA, PAI-1,
      and tissue kallikreins hK5-8, 10, 11, and 13 in extracts of 142 primary tumor
      tissue specimens from ovarian cancer patients and studied the strength of
      association between protein expression levels of these tumor tissue-associated
      factors. uPA, PAI-1, hk5, and hk8 were related to FIGO stage; hK5 expression was
      higher in FIGO III/IV than in FIGO I/II patient tissues. PAI-1 and hk5 differed
      significantly according to nuclear grading; expression of hK5 was higher in G3
      than in G1/2 tumors. Associations between uPA, PAI-1, and the tissue kallikreins
      were weak. There were strong pairwise correlations within the cluster of tissue
      kallikreins hK5, 6, 7, 8, 10, and 11, but their bivariate distributions depended
      on nuclear grading. These results support the notion that several tissue
      kallikreins are co-expressed in ovarian cancer patients, substantiating the
      existence of a steroid hormone-driven tissue kallikrein cascade in this disease.

PMID- 16895484
TI  - Heparin modulation of human plasma kallikrein on different substrates and
      inhibitors.
AB  - The interplay of different proteases and glycosaminoglycans is able to modulate
      the activity of the enzymes and to affect their structures. Human plasma
      kallikrein (huPK) is a proteolytic enzyme involved in intrinsic blood clotting,
      the kallikrein-kinin system and fibrinolysis. We investigated the effect of
      heparin on the action, inhibition and secondary structure of huPK. The catalytic
      efficiency for the hydrolysis of substrates by huPK was determined by Michaelis
      Menten kinetic plots: 5.12x10(4) M-1 s-1 for acetyl-Phe-Arg-p-nitroanilide,
      1.40x10(5) M-1 s-1 for H-D-Pro-Phe-Arg-p-nitroanilide, 2.25x10(4) M-1 s-1 for Abz
      Gly-Phe-Ser-Pro-Phe-Arg-Ser-Ser-Arg-Gln-EDDnp, 4.24x10(2)M-1 s-1 for factor XII
      and 5.58x10(2) M-1 s-1 for plasminogen. Heparin reduced the hydrolysis of
      synthetic substrates (by 2.0-fold), but enhanced factor XII and plasminogen
      hydrolysis (7.7- and 1.4-fold, respectively). The second-order rate constants for
      inhibition of huPK by antithrombin and C1-inhibitor were 2.40x10(2) M-1 s-1 and
      1.70x10(4) M-1 s-1, respectively. Heparin improved the inhibition of huPK by
      these inhibitors (3.4- and 1.4-fold). Despite the fact that huPK was able to bind
      to a heparin-Sepharose matrix, its secondary structure was not modified by
      heparin, as monitored by circular dichroism. These actions may have a function in
      the control or maintenance of some pathophysiological processes in which huPK
      participates.

PMID- 16895487
TI  - Proceedings of the Varese Update on Surgical Infections. March 30-April 1, 2006.
      Induno Olona, Italy.

PMID- 16895485
TI  - Adaptation of the behaviour of an aspartic proteinase inhibitor by relocation of
      a lysine residue by one helical turn.
AB  - In addition to self-inhibition of aspartic proteinase zymogens by their intrinsic
      proparts, the activity of certain members of this enzyme family can be modulated
      through active-site occupation by extrinsic polypeptides such as the small IA3
      protein from Saccharomyces cerevisiae. The unprecedented mechanism by which IA3
      helicates to inhibit its sole target aspartic proteinase locates an i, i+4 pair
      of charged residues (Lys18+Asp22) on an otherwise-hydrophobic face of the
      amphipathic helix. The nature of these residues is not crucial for effective
      inhibition, but re-location of the lysine residue by one turn (+4 residues) in
      the helical IA3 positions its side chain in the mutant IA3-proteinase complex in
      an orientation essentially identical to that of the key lysine residue in zymogen
      proparts. The binding of the extrinsic mutant IA3 shows pH dependence reminiscent
      of that required for the release of intrinsic zymogen proparts so that activation
      can occur.

PMID- 16895486
TI  - Cathepsins L and S are not required for activation of dipeptidyl peptidase I
      (cathepsin C) in mice.
AB  - The cysteine protease dipeptidyl peptidase I (DPPI) activates granule-associated
      immune-cell serine proteases. The in vivo activator of DPPI itself is unknown;
      however, cathepsins L and S are candidates because they activate pro-DPPI in
      vitro. In this study, we tested whether cathepsins L and S activate pro-DPPI in
      vivo by characterizing DPPI activity and processing in cells lacking cathepsins L
      and S. DPPI activity, and the relative size and amounts of DPPI heavy and light
      chains, were identical in mast cells from wild-type and cathepsin L/S double-null
      mice. Furthermore, the activity of DPPI-dependent chymase was preserved in
      tissues of cathepsin L/S double-null mice. These results show that neither
      cathepsin L nor S is required for activation of DPPI and suggest that one or more
      additional proteases is responsible.

PMID- 16895488
TI  - Effects of local and systemic warming on postoperative infections.
AB  - BACKGROUND: There is increasing recognition that attention to optimal perfusion
      and oxygenation, normothermia, and normoglycemia is associated with low
      postoperative infection rates. The results of several studies on temperature
      maintenance will be presented. METHODS: In a test of the value of systemic
      warming, patients undergoing major orthopedic, general, or urologic surgery were
      randomized to standard care with or without systemic warming using a disposable
      forced warm-air blanket. The addition of perioperative warming using a conductive
      carbon polymer mattress and overblanket to intraoperative warming was studied in
      patients undergoing major elective abdominal surgery. In a study of local
      warming, patients undergoing elective clean-wound surgery were randomized to
      local warming or non-warming. To determine the contribution of heat to
      eradication of methicillin-resistant Staphylococcus aureus, patients with stage
      III-IV pressure sores were randomized to receive or not receive local warming
      along with standard care. RESULTS: The intraoperative improvement of cutaneous
      blood flow and oxygen tension in the systemically warmed group improved tissue
      viability and reduced the incidence of pressure sores. A statistically
      significant reduction in morbidity and mortality was found in the patients having
      the conductive mattress as well as an overblanket. Similar findings are being
      reported from studies of systemic warming as an adjunct to resuscitation of
      patients presenting with abdominal pain and elderly patients admitted after a
      fall or with a suspected fractured femoral neck. Local warming with non-contact
      radiant heat was as good as systemic warming in preventing surgical site
      infections. CONCLUSIONS: Attention to keeping patients warm, together with
      maintenance of optimal perfusion and oxygenation and euglycemia, represents a
      simple effective guideline. Several methods of warming are available for use
      during transport and resuscitation and to achieve perioperative normothermia.

PMID- 16895489
TI  - Infections after living-donor liver transplantation.
AB  - BACKGROUND: Despite greater awareness of organ donation among the general public,
      the supply of cadaveric organs has fallen short of identified needs. Living-donor
      liver transplantation (LDLT) is an effective means of overcoming the shortage of
      adult organs, as outcomes are now comparable to those of cadaveric donor liver
      transplantation. METHODS: From January, 2002 through January, 2006, 40 LDLTs were
      performed at our center. With two exceptions, the donor was a first-degree
      relative of the recipient; all donors were in excellent health with good hepatic
      function and morphology. All but two donors contributed the right lobe.
      Infections in the donors and recipients were analyzed. RESULTS: Clinically
      relevant infections occurred in three donors. In the recipients, the infections
      did not differ significantly from those experienced by recipients of cadaveric
      organs in terms of risk factors (e.g., poor graft function, re-transplantation,
      surgical complications such as bile duct stenosis, or vascular anastomotic
      stenosis) or type of infection. Cholangitis was the most frequent infection,
      leading to septic shock in five of the 14 patients with infections; intra
      abdominal infections related to surgical complications led to septic shock in
      three additional patients. The other most commonly observed infections were
      urinary tract infections (n=10) and pneumonia (n=3). CONCLUSIONS: Living-donor
      liver transplantation offers hope to patients with end-stage liver disease in
      geographic areas where the waiting time mortality is high and available organs
      from deceased donors fall short of the population's need.

PMID- 16895490
TI  - Infective complications in laparoscopic surgery.
AB  - BACKGROUND AND PURPOSE: One of the main benefits of minimally invasive surgery
      compared with open surgery is the significant reduction in the incidence of
      postoperative infections. Possible explanations include the smaller incision,
      minimal use of central venous catheters for parenteral nutrition, faster
      mobilization, reduction in postoperative pain, and better preservation of immune
      system function with a limited inflammatory response to tissue injury. We compare
      the incidence of postoperative infections after the most common laparoscopic
      surgical procedures with that after the corresponding open operation, and review
      the possible mechanisms behind these results. METHOD: Review of the pertinent
      literature. RESULTS: Several randomized controlled trials (RCTs), as well as most
      retrospective studies, show a significant reduction in incisional complications
      with laparoscopic cholecystectomy in comparison with open surgery (mean 1.1% vs.
      4%), as well as in urinary tract and pulmonary infections. In colorectal
      resection, laparoscopic surgery was characterized by a significant reduction in
      surgical site infections (mean 5% vs. 9.5%), and the infections that did occur
      tended to be less severe. Again, there were fewer urinary and pulmonary
      infections postoperatively. Acute appendicitis represents an interesting setting
      to study the effect of minimally invasive surgery on infections, as it involves a
      potentially contaminated field. Most of the results confirm that the rates of
      surgical site (mean 2% versus 8%) and respiratory (mean 0.3% versus 3%)
      infections favor laparoscopic surgery, but minimally invasive surgery seems to be
      characterized by a higher incidence of postoperative intra-abdominal abscess. The
      laparoscopic approach to splenectomy is clearly superior to standard laparotomy
      in terms of postoperative complications, including infections, although the rate
      of overwhelming postsplenectomy infection (OPSI) remains similar because this
      complication is related more to spleen removal than to the surgical approach.
      CONCLUSIONS: Most of the literature is in agreement that laparoscopic surgery is
      associated with better preservation of immune function and a reduction of the
      inflammatory response compared with open surgery. The rate of postoperative
      infections seems to be significantly lower.

PMID- 16895492
TI  - Surgical site infections after thyroidectomy.
AB  - BACKGROUND: The history of thyroid surgery starts with Billroth, Kocher, and
      Halsted, who developed techniques for thyroidectomy between 1873 and 1910. Before
      1950, the operative mortality rate approached 50%. The advent of general
      anesthesia and antisepsis and the development of fine hemostatic instruments
      rendered thyroid surgery safer, but the potential persists for life-threatening
      complications. This study was designed to identify specific risk factors for the
      development of surgical site infections (SSIs); to define high-risk patients; to
      determine the causative organisms; to illustrate the clinical presentation,
      treatment, and outcome; and to establish management guidelines. METHODS: A
      prospective analysis was carried out of complications affecting 241 consecutive
      patients (mean age 65+/-19 years; 76% female) undergoing cervical exploration for
      thyroid disease from 2000 to 2005, with particular attention to infection, and
      the pertinent literature was reviewed. RESULTS: Surgical site infections (SSI)
      affected 2% of patients. The risk of infection depended mainly on the quality of
      pre-operative and post-operative care and on whether there was a break in sterile
      technique. The use of drains and pre-operative antibiotics did not affect the
      incidence of SSI. No pre-operative factor foreshadowed this complication, and the
      definition of a high-risk population remains obscure. Surgical site infections
      lengthened the hospital stay. CONCLUSIONS: Effort should be made to improve
      sterile technique. Appropriate antibiotic coverage is indicated when infection
      develops post-operatively. The most important element in the management of SSI is
      adequate drainage of the incision once infection develops.

PMID- 16895491
TI  - Long-term results and quality of life of patients undergoing sequential surgical
      treatment for severe acute pancreatitis complicated by infected pancreatic
      necrosis.
AB  - BACKGROUND: Infected pancreatic necrosis (IPN) is one of the most severe
      complications of acute pancreatitis (AP). Sequential surgical debridement
      represents one of the most effective treatments in terms of morbidity and
      mortality. The aim of this paper is to describe the quality of life and long-term
      results (e.g., nutritional, muscular, and pancreatic function) of patients
      treated by sequential necrosectomy at the Department of Surgery of the University
      of Insubria (Varese, Italy). METHODS: Data were collected on patients undergoing
      sequential surgical debridement as treatment for IPN. The severity of AP was
      evaluated using the Ranson criteria, the Acute Physiology and Chronic Health
      Evaluation (APACHE II) Score, and the Sepsis Score, as well as the extent of
      necrosis. The surgical approach was through a midline or subcostal laparotomy,
      followed by exploration of the peritoneal cavity, wide debridement, and
      peritoneal lavage. The abdomen was either left open or closed partially with a
      surgical zipper, with multiple re-laparotomies scheduled until debridement of
      necrotic tissue was complete. The long-term evaluation focused on late morbidity,
      performance status, and abdominal wall function. RESULTS: In the majority of
      patients (68%), mixed flora were isolated. Pseudomonas aeruginosa was the
      microorganism identified most commonly (59%), often associated with Candida
      albicans or C. glabrata. The mean total hospital stay was 71+/-38 days (range 13
      146 days), of which 24+/-19 days (range 0-66 days) were in the intensive care
      unit. Eight patients died, the deaths being caused by multiple organ dysfunction
      syndrome in seven patients and hemorrhage from the splenic artery in one. Normal
      exocrine and endocrine pancreatic function was observed in 28 patients (88%). At
      discharge, four patients had steatorrhea, which was temporary. Eight patients
      (23%) developed pancreatic pseudocysts, and in six, cystogastostomy was
      performed. Most patients (29/32, 91%) developed a post-operative hernia, but only
      five required surgical repair. All patients had a Short Form (SF)-36 score>60%,
      and 20 of the 32 patients (68%) had scores>70-80% (good quality of life). The
      worst scores were related to alcoholic pancreatitis. CONCLUSIONS: The degree of
      pancreatic failure (exocrine and endocrine function) is not related to the amount
      of pancreatic necrosis. Even with a need for repeated laparotomy and multiple
      surgical procedures, the abdominal wall capacity as well as long-term quality of
      life remain excellent.

PMID- 16895493
TI  - Surgical site infections in day surgery settings.
AB  - BACKGROUND: Because major complications are rare in day surgery, minor
      morbidities such as surgical site infections, which become evident only after
      patient discharge, have a major impact on the perceived quality of care. We
      performed an audit of such infections over a oneyear period. METHODS: All
      procedures were performed in a multidisciplinary day surgery setting. There were
      155 inguinal hernia repairs, 44 excisions of lipomas, and 27 excisions of
      pilonidal cysts. All patients received antibiotic prophylaxis according to a
      rotation protocol. RESULTS: One patient (0.65%) operated on for inguinal hernia
      developed a deep incisional infection caused by Staphylococcus schleiferi. The
      patient was treated using selective antibiotics, and complete recovery ensued.
      One patient (2.27%) who underwent excision of a lipoma revealed developed a deep
      incisional infection associated with fever (39 degrees C) caused by
      Staphylococcus aureus. He was treated by daily antibiotics and application of
      dressings for two weeks and recovered. One patient (3.7%) treated for pilonidal
      cyst developed a deep incisional surgical site infection. A group A Streptococcus
      was isolated, and he received an intravenous antibiotic for ten days. In the
      seven patients treated for pilonidal cyst with the wound left open, swab
      specimens were taken because of persisting local pain, and the following bacteria
      were found: Pseudomonas aeruginosa, Escherichia coli, Staphylococcus epidermidis,
      Proteus vulgaris, and Streptococcus constellatus. No antibiotic therapy was
      given, and local wound care led to complete recovery. CONCLUSION: In our day
      surgery unit, the rates of surgical site infection are similar to those described
      in the literature. Continuing audit is essential to maintain and improve the
      quality and standard of the surgery provided. Prevention of surgical site
      infection is very much the responsibility of the persons working in the operating
      theater. Therefore, it is vital not only to apply strict regulations concerning
      everyday management but also to maintain a high degree of motivation among the
      personnel.

PMID- 16895495
TI  - Microbiology of postoperative infections.
AB  - BACKGROUND: Surgical infections, accounting for approximately one quarter of all
      nosocomial infections, contribute to longer hospital stays and higher medical
      costs. Clinical failure of antibiotic treatment often is associated with
      increasing drug resistance. METHODS: Non-duplicated microbial isolates obtained
      at our institution from surgical patients were identified and tested for
      antimicrobial susceptibility using the Sceptor system in 2001-2002 and the
      Phoenix system in 2003-2005. Epidemiologic data were extracted using Epicenter
      and Powerlab. During selected periods, genetic and biochemical characterization
      was performed by pulsed-field gel electrophoresis, colony blot hybridization,
      gene amplification and sequencing, isoelectric focusing, and enzyme kinetics.
      RESULTS: The specimens were most commonly isolated from infections at surgical
      sites (24.0%), the urinary tract (19.0%), and blood stream (10.6%). Isolates of
      Escherichia coli showed an increasing prevalence of resistance to penicillins,
      third-generation cephalosporins, ciprofloxacin, and gentamicin, whereas the
      prevalence of resistant Staphylococcus aureus generally declined. Highly
      aggressive multi-drug-resistant (MDR) Pseudomonas aeruginosa strains were
      widespread, although colistin remained effective in 100% of cases. A significant
      increase was seen in infections attributable to S. epidermidis and Candida
      albicans. The overall number of Enterobacteriaceae carrying extended-spectrum
      beta-lactamases increased continuously, and new resistance traits emerged. It
      appeared that the TEM-92 determinant moved from Enterobacteriaceae to
      nonfermenting gram-negative rods such as Acinetobacter baumannii. CONCLUSION: The
      number and type of antimicrobial-resistance determinants are increasing.

PMID- 16895496
TI  - Postoperative fever.
AB  - BACKGROUND: Fever is common in surgical patients. The list of potential causes is
      long and includes many noninfective etiologies. CAUSES: Only about 40% of fever
      episodes in hospitalized patients are caused by infection. Any fever in a
      surgical patient is a cause for concern. New or continuing fever more than three
      days after surgery should raise a strong suspicion of persistent illness or a new
      complication. On rare occasions, these fevers can be attributed to potentially
      life-threatening occult infections, including acute cholecystitis, antibiotic
      related pseudomembranous colitis, systemic candidiasis, or transfusion-related
      cytomegalovirus disease. A change in the microbiology of postoperative infections
      has also been noticed, characterized by a greater incidence of infections caused
      by methicillin-resistant Staphylococcus aureus, by polymicrobial flora, and by
      fungi. TREATMENT: Control of nosocomial infections has become more challenging
      recently because of widespread bacterial resistance to antibiotics and to more
      frequent surgical indications in elderly patients at higher risk. Early
      recognition and appropriate treatment of these infections relieves anxiety,
      reduces hospital costs, and increases patient survival rates. CONCLUSIONS: The
      workup and therapy for the individual patient may differ, depending on the
      underlying disease and clinical appearance and the clinician's suspicion for
      infection. Subsequent testing should be based on the clinical findings. Perhaps
      more money is wasted in the evaluation of early postoperative fever than on any
      other aspect of postoperative care.

PMID- 16895497
TI  - Health care-associated infections.
AB  - BACKGROUND: The incidence of postoperative infections in surgery can be reduced
      by 20% to 34% through adoption of "safe" patient care practices. Moreover, some
      of the recently highlighted epidemiologic features of infections in surgery, such
      as the increasing prevalence of antibiotic-resistant organisms, are strongly
      associated with questionable clinical choices. In recent years, several
      governments and scientific institutions have launched initiatives aimed at
      improving the safety of surgery, a key component of which is the availability of
      surveillance data. METHODS: In 2003, an audit was performed in the Emilia-Romagna
      region of Italy on a random sample of general, orthopedic, and gynecologic
      surgical units to explore the knowledge, perceptions, and practices of surgeons
      and nurses regarding control of surgical site infections (SSI). RESULTS: The
      Emilia-Romagna regional audit found good agreement between the infectioncontrol
      standards and knowledge (70%), claimed practices (73%), and observed practices
      (78%). Surgical hand antisepsis was applied consistently, and surgical attire was
      used widely, but surgeons and nurses paid little attention to keeping operating
      room doors closed and limiting the number of people. Handwashing and sterile
      technique for postoperative incision care were the recommendations least
      frequently followed. CONCLUSIONS: Greater attention to proven methods of
      infection control and availability of surveillance data should reduce the
      incidence of SSI.

PMID- 16895498
TI  - Vascular catheter-related infection and sepsis.
AB  - BACKGROUND: Catheter-related sepsis is a clinical syndrome characterized by the
      presence of a catheter-associated infection along with a systemic inflammatory
      response. The continual increase in the use of central venous catheters (CVCs)
      has been associated with a substantial risk of infectious complications that
      prolong the hospital stay and increase costs. METHODS: The literature on CVCs was
      reviewed to determine the incidence of catheterrelated sepsis, its diagnosis, and
      the role of biofilms in pathogenesis. RESULTS: The European Sepsis Group recently
      reported that 28% of CVC infections in intensive care unit patients were
      associated with sepsis, 24% with severe sepsis, and 30% with septic shock.
      Clinical diagnosis remains difficult. After CVC insertion, the intravascular
      portion of the device is covered rapidly by a thrombin layer, rich in host
      derived proteins, that forms a conditioning film and promotes surface adherence
      of microbial colonizers. These microorganisms then enter their sessile mode of
      growth, secreting an exopolysaccharide slime within which organism density is
      regulated by quorum-sensing molecules. Microorganisms are dispersed in clumps
      that can become septic emboli. Antiadhesive, antiseptic, and antibiotic coatings
      of catheters have demonstrated only modest clinical efficacy. CONCLUSION: Our
      group is involved in the design and in vitro assessment of new polymeric matrices
      for controlled release of antimicrobial molecules, and in comparative clinical
      studies of conventional versus antibiotic-coated or -impregnated catheters.

PMID- 16895499
TI  - Nutrition and infections.
AB  - BACKGROUND: Patients with cancer suffer alterations of their metabolic state and
      nutritional depletion. This review was designed to evaluate the effect of
      different nutritional regimens on surgical outcomes. METHOD: Review of the
      literature on parenteral and enteral nutrition and immunonutrition in patients
      with gastrointestinal cancer undergoing major surgery. The outcome measures were
      postoperative complication rate and length of hospital stay. RESULTS:
      Postoperative enteral nutrition reduced significantly the rate of postoperative
      complications compared with parenteral feeding only in malnourished subjects.
      Several metaanalyses and randomized trials showed that preoperative and
      perioperative use of an enteral formula containing arginine and omega-3 fatty
      acids has a significant beneficial effect on surgical outcome in both well
      nourished and malnourished patients. CONCLUSIONS: Enteral immunonutrition should
      represent the first choice to nourish surgical subjects.

PMID- 16895500
TI  - Mediator responses in surgical infections.
AB  - BACKGROUND: Surgical infections, and sepsis in particular, are characterized by
      extensive release of mediators. Our laboratories have been interested in
      understanding how these substances contribute to morbidity and mortality during
      various stages of surgical infections in order to develop new and more effective
      therapeutics and treatment strategies. METHODS: In a series of in vitro studies,
      human plasma was exposed to lipopolysaccharide (LPS), and whole blood was treated
      with peptidoglycan from Staphylococcus aureus. The activity of peptidoglycan also
      was studied in the rat, and LPS infusion was tested in dog and pig models. In a
      clinical study, the relation of serum LPS to multiple organ dysfunction and
      failure was studied in patients in the surgical intensive care unit. RESULTS:
      Exposure of plasma to LPS led to formation of bradykinin, activation of the
      plasma kallikrein-kinin system, and reduction of kallikrein inhibitor capacity.
      The coagulation, fibrinolysis, and complement cascades were activated.
      Peptidoglycan caused rapid release of tumor necrosis factor-alpha, interleukin
      1beta, and interleukin-6 from macrophages and activation of the genes encoding
      pro-inflammatory and anti-inflammatory cytokines. In the rat, peptidoglycan
      induced cytokine release, caused liver and kidney dysfunction, and induced matrix
      metalloproteinase-9 (MMP-9) activity in the liver and lung. In the dog and pig,
      LPS caused substantial activation of plasma proteases. Clinically, a finding of
      LPS in the plasma was associated with multiple organ dysfunction and failure.
      These patients also revealed substantial activation of the plasma cascade
      systems, as well as systemic cytokine release. CONCLUSION: On the basis of these
      observations, we developed a monitoring system to recognize early signs of
      infection.

PMID- 16895501
TI  - Blood transfusions and postoperative infections in patients undergoing elective
      surgery.
AB  - BACKGROUND: Postoperative infections result from the interactions of bacteria,
      the surgical technique, and host defense mechanisms. Thus, identifying single
      determinant factors has proved difficult. MAGNITUDE OF THE RISK: In a recent
      survey of 2,809 colorectal resections, transfusion was the single most powerful
      risk factor for postoperative infection. In patients undergoing primary hip or
      knee prosthesis insertion, the transfusion of allogeneic blood increased the risk
      of a deep-seated infection by a factor of 12. MECHANISMS: Several host defense
      mechanisms are impaired by blood products. The initial hypothesis incriminated
      the transfused white blood cells, but this paradigm has since been challenged.
      The effects of free serum iron, the blood storage time, and the presence in
      stored blood of bioactive substances such as inhibitors of metalloproteinase-1
      may also be important. CONCLUSION: It is worth pursuing efforts to emphasize
      autologous blood transfusion and the reinfusion of shed blood as blood
      conservation strategies, as these practices reduce the risk of infectious
      complications.

PMID- 16895502
TI  - Perioperative antibiotic prophylaxis: a critical review.
AB  - BACKGROUND: The value of perioperative prophylaxis is established for clean
      contaminated procedures. For clean surgery, prophylaxis traditionally has been
      reserved for prosthetic device implantation procedures. METHODS: Review of
      pertinent English-language literature. CURRENT RECOMMENDATIONS: Evidence suggests
      that prophylactic antibiotics are advisable for at least some non-prosthetic
      procedures and that glycopeptides might have a role for major prosthetic surgery
      in units with a high prevalence of methicillin-resistant Staphylococcus aureus.
      In clean-contaminated surgery, cefazolin is recommended, although not for
      colorectal procedures or obstetric/gynecologic surgery that requires anti
      anaerobic coverage. CONCLUSION: Antibiotic prophylaxis is generally
      overprescribed (i.e., given for too long). Short-duration prophylaxis is
      effective and safe.

PMID- 16895503
TI  - Impact of postoperative infections on survival in colon cancer patients.
AB  - PURPOSE: We investigated the prognostic significance of postoperative infections
      for the outcome of 192 patients with colon cancer. METHODS: The 5-year survival
      rates were analyzed by the Kaplan-Meier technique. Univariate and multivariate
      analyses were done to evaluate prognostic variables using Cox's proportional
      hazard model. RESULTS: Forty-three patients developed deep incisional or
      organ/space surgical site infections. The groups with and without infection were
      comparable. Multivariate analysis showed that only Dukes' stage (p=0.048) and
      postoperative infection (p=0.011) were independently associated with outcome. In
      patients with infective complications, the survival rate was significantly lower
      than in subjects without infection (log rank p=0.0004). CONCLUSIONS: These
      results stress the importance of evaluating variables other than the classical
      tumor stage in predicting long-term cancer outcome.

PMID- 16895504
TI  - New trends in prosthesis infection in cardiovascular surgery.
AB  - BACKGROUND: Adult cardiovascular surgery entails, in many cases, the use of some
      kind of prosthesis. Among the potential complications, prosthetic device
      infection is one of the most devastating in incidence, as well as in prognosis
      and damage to surrounding tissues. RESULTS: The most common bacterial agents in
      vascular and cardiac prosthetic device infections are Staphylococcus aureus and
      S. epidermidis among gram-positive bacteria and Escherichia coli, Proteus
      mirabilis, and Pseudomonas aeruginosa among gram-negative bacteria. CONCLUSION:
      The alternative modalities of treatment for prosthetic device infection encompass
      partial or total explantation of the prosthesis and its replacement with an
      infection-resistant graft (e.g., homologous tissue, autologous tissue, or
      synthetic prosthesis bonded with antibiotics).

PMID- 16895505
TI  - Infected pancreatic necrosis.
AB  - BACKGROUND: Infected pancreatic necrosis is a late infective complication of
      acute necrotizing pancreatitis in which infection tends to spread from the
      pancreas to the peripancreatic tissues, retroperitoneum, and, more rarely, the
      peritoneal cavity. Severe and rapid deterioration of the clinical condition may
      lead to septic shock and multiple organ dysfunction syndrome. CAUSATIVE
      ORGANISMS: The microorganisms most frequently isolated in cases of acute
      bacterial pancreatitis have been historically gram-negative bacteria of enteric
      origin. However, gram-positive cocci are isolated with increasing frequency.
      Enterococci are the single most commonly isolated species. TREATMENT: Aggressive
      multimodal therapy in the early stage of severe necrotizing pancreatitis improves
      survival; patients with infective complications tend to die later from multiple
      organ dysfunction syndrome. Initially, the treatment consists of fluids,
      analgesics, and oxygen supplementation. Surgical debridement should be limited to
      proved infections and delayed as long as possible to allow necrotic tissue to
      become demarcated. When surgery is necessary, blunt debridement of necrotic
      tissues is the procedure largely utilized and usually is not accompanied by
      excessive bleeding. Pancreatic resection should be reserved for massive necrosis
      of the gland substance. In many situations, the abdominal incision can be closed
      primarily. Treatment by the "open abdomen" technique should be reserved for those
      patients in whom further laparotomies are planned, mainly because of incomplete
      unsatisfactory debridement or uncontrolled bleeding that necessitates packing of
      the lesser sac. CONCLUSION: Modern management techniques have reduced the
      mortality of infected pancreatic necrosis to 15-20% from historical rates that
      were twice as high. Aggressive resuscitation and surveillance of infection are
      crucial for successful outcomes, although fewer patients are undergoing surgical
      debridement.

PMID- 16895507
TI  - Postoperative fungal infections.
AB  - BACKGROUND: A substantial proportion of patients become colonized with Candida
      spp. after surgery, but only a minority subsequently develop invasive
      candidiasis. However, clinical signs of severe infection manifest only late,
      presenting a challenge for diagnosis. Better knowledge of the pathogenesis of
      candidiasis and new compounds have improved the prognosis but also encouraged the
      emergence of non-albicans strains of Candida. DIAGNOSIS: Genotyping has confirmed
      that colonization from endogenous sources is responsible for the majority of
      cases of invasive candidiasis. Nevertheless, even if a large proportion of
      surgical patients becomes colonized, only a minority develop invasive
      candidiasis. This subgroup is difficult to identify, and many clinicians treat
      systematically all colonized patients, a practice that may select resistant
      strains. Biological tools have not improved the diagnosis, and the threshold
      between colonization and infection remains to be determined. The colonization
      index, defined as the ratio of the number of sites colonized by Candida strains
      to the number of sites tested, is a useful tool. CONCLUSIONS: After surgery,
      empiric treatment must be restricted to patients in whom the dynamics of Candida
      colonization predict a very high risk of invasive candidiasis. Prophylaxis should
      be limited to the small group of patients in whom its efficacy is proven.

PMID- 16895506
TI  - Host defense mechanisms against pathogens.
AB  - BACKGROUND AND PURPOSE: The body is under constant assault by potentially harmful
      microbes. Both innate and adaptive immune responses counteract the action of
      pathogens. METHOD: Review of the pertinent literature. RESULTS: The innate
      response is focused mainly on physically eliminating the pathogens, mostly by
      phagocytosis, while the adaptive response reacts specifically to, and
      neutralizes, a given pathogen and maintains a memory of it for safer and faster
      elimination on subsequent encounters. CONCLUSION: The basic mechanisms of
      pathogen elimination by the immune system and some mechanisms of evasion of the
      immune response by pathogens are discussed.

PMID- 16895508
TI  - Prospective study of infection risk factors in 988 lung resections.
AB  - PURPOSE: To evaluate the incidence of surgical site infections (SSI), as related
      to risk factors, in patients undergoing lung resections (LR). METHODS: We
      evaluated 988 consecutive patients prospectively who underwent LR between 1996
      and 2005 at the Center for Thoracic Surgery of the University of Insubria,
      Varese, Italy. Patients were divided into four groups: Pneumonectomy (n=104),
      lobectomy/bi-lobectomy (n=438), wedge resection by thoracotomy (n=155), and wedge
      resection by video-thoracoscopy (VATS) (n=291). The recorded risk factors for SSI
      were hemoglobin concentration, serum albumin concentration, lymphocyte count,
      percentage of predicted forced expiratory volume in 1 sec (FEV1), duration of
      surgery, blood transfusion, age>70 years, and comorbidity. The postoperative SSIs
      (superficial and deep incisional SSI, pneumonia, empyema) were recorded in they
      occurred within 30 days, and the final outcome was recorded. RESULTS:
      Postoperative infections were found in 141 patients (14.3%) and included 166
      thoracic infections, among them 32 incisional SSIs (3.2%), 103 cases of pneumonia
      (10.4%); and 24 empyemas (2.4%). The overall incidence of SSI was significantly
      lower in patients having wedge resections by VATS (5.5%) than in the other three
      groups (17.9%) (p<0.001). The overall mortality rate was 1.2% (12/988), of which
      six deaths (0.6%) were caused by complications of infection. The infection rate
      correlated with duration of surgery>180 min, age>70 years, serum albumin<3.5
      g/dL, and the presence of any comorbidity. Moreover, 18% of patients with
      FEV1>70% had postoperative pneumonia, a significant increase (p<0.01) compared
      with patients with FEV1>or=70%. CONCLUSIONS: In this prospective study, the SSI
      rate after LR was 14.3%, and the 30-day operative mortality rate was 1.2%, with
      most of the deaths caused by pneumonia. After VATS LR procedures, the incidence
      of SSI was lower at 5.5%. Finally, SSI correlated with the duration of surgery,
      serum albumin, concurrent comorbidity, age, and FEV1.

PMID- 16895509
TI  - Mechanical bowel preparation for colorectal surgery.
AB  - BACKGROUND: Nosocomial infections are the most frequent complications of surgical
      patients. Most surgical site infections (SSI) are acquired intraoperatively and
      arise from the flora of the patient's skin, gastrointestinal tract, or mucous
      membranes. Although preoperative mechanical cleansing of the bowel is considered
      by many surgeons a cornerstone of modern elective colorectal surgery and, in
      association with antibiotic prophylaxis, a fundamental component of an intestinal
      antisepsis program, many surgeons do not perform preoperative mechanical
      preparation routinely. METHODS: Review of the pertinent literature. RESULTS: Some
      recent randomized trials and a Cochrane review found no proof that mechanical
      bowel preparation reduces the risk of complications after elective colorectal
      surgery. Indeed, there is some evidence that this intervention is associated with
      a higher rate of anastomotic leakage and wound complications. CONCLUSIONS: The
      dogma that mechanical bowel preparation is necessary before elective colorectal
      surgery may need to be reconsidered. On the other hand, such preparation
      decreases operating time by improving bowel handling during construction of the
      anastomosis. Moreover, it is helpful when intestinal palpation will be necessary
      for identification of a lesion.

PMID- 16895510
TI  - Recommendations and reports about central venous catheter-related infection.
AB  - BACKGROUND: Central venous catheters (CVCs) are used to deliver a variety of
      therapies, as well as for measurement of hemodynamic parameters. The major
      associated complication is catheter-related blood stream infection (CRBSI).
      METHOD: Review of the pertinent English-language literature. RESULTS: The
      incidence of CRBSI depends on how such infections are defined. Generally, the
      term includes all BSIs in patients with CVCs when other sources can be excluded,
      and if a culture of the catheter tip demonstrates a substantial number of
      colonies of the organism found in the blood stream. Important pathogenic
      determinants of catheter-related infection are the material of which the device
      is made and the intrinsic virulence of the organism. The site at which a catheter
      is placed influences the risk of infection. The types of organisms that most
      commonly cause hospital-acquired BSIs have changed over time. Migration of skin
      organisms at the insertion site into the cutaneous catheter tract with
      colonization of the catheter tip is the most common route of infection. Good hand
      hygiene before catheter insertion, combined with proper aseptic technique during
      its manipulation, provides protection against infection; maximal sterile barrier
      precautions during insertion reduce the incidence of CRBSI. Catheters that are
      coated or impregnated with antimicrobial or antiseptic agents can decrease the
      risk and the associated hospital costs. No studies have demonstrated that oral or
      parenteral antibacterial or antifungal drugs reduce the incidence of CRBSI in
      adults. Use of anticoagulants might have a role in the prevention of CRBSI.
      Catheter replacement at scheduled intervals has not lowered rates of local or
      systemic complications. CONCLUSIONS: Central venous catheters are used commonly
      to deliver a variety of therapies, such as large amounts of fluid or blood
      products during surgery or in intensive care units, chemotherapy, and parenteral
      nutrition, as well as for measurement of hemodynamic variables. The major
      complication associated with CVCs is CRBSI.

PMID- 16895511
TI  - Organ dysfunction in patients with severe sepsis.
AB  - BACKGROUND: Severe sepsis is defined as sepsis plus organ dysfunction. There is a
      need to quantify this dysfunction, and several scoring systems have been
      developed. METHOD: Review of the pertinent English-language literature. RESULTS:
      Early scoring of organ failure simply counted the number of failing organs, but
      the degree of dysfunction is an important variable. The first system to grade
      dysfunction was the multiple organ dysfunction score (MODS). The drawback of MODS
      is the variable used to quantify cardiovascular failure. To alleviate this
      limitation, the Brussels score was developed. However, it, too, was suboptimal
      and was replaced by the sequential or sepsis-related organ failure assessment
      (SOFA) score. There is a clear correlation between the total SOFA score and the
      mortality rate, and in certain studies, the total SOFA score was at least as good
      as traditional methods of predicting death. A key advantage of these simple
      scores is that they can be repeated to follow the course of organ dysfunction.
      The evolution of the SOFA score has been used to demonstrate the effects of
      various therapeutic interventions. CONCLUSION: Quantifying organ dysfunction in
      patients with sepsis can assist in assessing prognosis and determining treatment
      effectiveness. The simplicity, reliability, and reproducibility of current scores
      facilitate their widespread use.

PMID- 16895512
TI  - Progress in the management of sepsis: the surviving sepsis campaign.

PMID- 16895514
TI  - Ventilator-associated pneumonia: what is new?
AB  - BACKGROUND: Ventilator-associated pneumonia (VAP) is the most frequent intensive
      care unit (ICU)-acquired infection among patients receiving mechanical
      ventilation. Failure to initiate appropriate and adequate therapy (i.e., the
      etiologic organism is sensitive to the therapeutic agent, the dose is optimal,
      and the route of administration is correct) promptly in patients with VAP has
      been associated consistently with higher mortality rates. However, effective
      antimicrobial therapy for patients with true VAP can be achieved while avoiding
      excessive antibiotic use and the emergence of multidrug-resistant strains in the
      ICU. METHOD: Review of the pertinent English-language literature. RESULTS:
      Antimicrobial therapy for patients with VAP should follow a two-stage process.
      The first stage is identifying true pneumonia rapidly and starting therapy with
      an empirical regimen that is likely to be appropriate. In general, this requires
      using broad-spectrum antibiotics in all patients in whom there is a possibility
      that the etiologic pathogen could be difficult to treat (e.g., multi-drug
      resistant pathogen). The second stage focuses on trying to achieve this objective
      without overusing and abusing antibiotics and combines a number of steps, such as
      stopping therapy in patients with a low probability of the disease, streamlining
      treatment once the etiologic agent is known, switching to monotherapy after three
      to five days, and shortening the duration of therapy to seven or eight days, as
      dictated by the patient's clinical response to therapy and information about the
      bacteriology of the infection. CONCLUSION: Although such a strategy seems a
      logical way to manage patients with VAP, data are still needed to determine how
      best to achieve this process.

PMID- 16895513
TI  - Efficacy and safety of drotrecogin alfa (activated) for the therapy of surgical
      patients with severe sepsis.
AB  - BACKGROUND: The efficacy of therapy with drotrecogin alfa (activated) (DrotAA)
      (recombinant human activated protein C) for surgical patients with severe sepsis
      has been questioned, and there is concern that patients who have undergone
      surgery recently may be at increased risk of bleeding complications from the
      drug. This review was performed to analyze recent data and clinical trends in the
      management of surgical patients with severe sepsis with respect to the efficacy
      and safety of therapy with DrotAA. METHODS: Review and synthesis of the pertinent
      English-language literature. RESULTS: Source control is the mainstay of therapy
      for surgical infections, including intraabdominal infections, whereas
      antibiotics, fluid resuscitation, and support of visceral organ function are
      necessary adjuncts. Therapy with DrotAA can be given to surgical patients, albeit
      with some delay (most protocols specify a 12-h wait after major surgery to
      mitigate the perceived increased risk of bleeding), but efficacy as well as
      safety have been questioned. In the pivotal PROWESS clinical trial, DrotAA
      therapy did not appear to be efficacious for surgical sepsis, but rigorous
      scrutiny of surgical indications and adequacy of source control by blinded
      reappraisal of the PROWESS database suggested that DrotAA therapy may be
      effective for surgical patients at high risk of death (Acute Physiology and
      Chronic Health Evaluation [APACHE] II score>or=25 points). Several comparable
      studies have now been aggregated in the INDEPTH database, which shows a
      significant reduction in mortality (OR 0.66; 95% CI 0.45-0.97) for therapy with
      DrotAA of surgical patients with severe sepsis and a high risk of death. The risk
      of bleeding is higher in surgical patients compared with DrotAA-treated non
      surgical patients, but there is a substantial improvement in survival with DrotAA
      treatment. In contrast, surgical patients at a lower risk of death do not benefit
      from therapy with DrotAA but are placed at risk for bleeding. CONCLUSION:
      Accumulating experience indicates that surgical patients with severe sepsis and a
      high risk of death (APACHE II>or=25 points) have a significantly lower mortality
      rate if treated with DrotAA. The increased risk of bleeding associated with
      therapy is acceptable given the clear improvement in survival. Surgical patients
      with sepsis who are at lower risk of death do not appear to benefit from therapy
      with DrotAA, which should be withheld in most circumstances because of the
      increased risk of bleeding.

PMID- 16895515
TI  - Antimicrobial treatment of sepsis.
AB  - BACKGROUND: Sepsis is a major cause of morbidity and death in hospitalized
      patients worldwide and one of the largest current challenges in critical care.
      METHOD: Review of the pertinent English-language literature. RESULTS: Treatment
      goals conventionally have included maintenance of systemic perfusion and
      eradication of sources of infection. Initial empiric antimicrobial regimen should
      be broad enough to cover all likely pathogens, as there is little margin for
      error in critically ill patients. CONCLUSION: A multidisciplinary team, including
      the critical care physician, the microbiologist, the infectious disease
      specialist, the surgeon, and the clinical pharmacologist, is necessary for
      optimal patient outcome.

PMID- 16895516
TI  - Risk factors for surgical infections.
AB  - BACKGROUND: Many risk factors for postoperative infections have been identified
      that can be used individually or in combination as scoring indices. METHODS:
      Infection risk scores can be applied in clinical practice to identify high-risk
      surgical patients, to indicate the need to implement risk-reduction strategies,
      and to stratify risk for comparison of outcome among different patient series.
      RESULTS: In the hierarchy of patient-related risk factors, serum albumin
      concentration and advanced age rank at the top of the list. Among the treatment
      related factors, the quality of the surgical technique is a most important
      determinant, although most surgical site infections are attributable to patient
      related risk factors rather than to flawed surgical care. Scoring systems can
      identify the patients at highest risk, thus prompting the implementation of
      therapy to improve modifiable conditions, but most clinicians outside the
      academic and research setting do not use them. Risk assessment also can be
      performed by expert clinical judgment. Discussion with the patient and informed
      consent are essential. CONCLUSIONS: Carefully collected scores of patient risk
      factors may be valuable to document the relations between the risk and the
      outcome of surgery. Ideally, each institution should select a validated scoring
      system to audit postoperative infectious morbidity and surgical performance in
      the various specialties.

PMID- 16895517
TI  - Increasing fungal infections in the intensive care unit.
AB  - BACKGROUND: Yeasts and molds now rank among the most common pathogens in
      intensive care units. Whereas the incidence of Candida infections peaked in the
      late 1970s, aspergillosis is still increasing. METHOD: Review of the pertinent
      English-language literature. RESULTS: Most factors promoting an invasive fungal
      infection are difficult to avoid because they are connected directly to treatment
      of the underlying disease. Antifungal treatment is often commenced on an empiric
      basis, whereas it might be preferable to adopt a strategy based on a diagnostic
      procedure able to demonstrate or exclude fungal disease. Polyenes have been the
      drugs of choice, but voriconazole is the new standard for aspergillosis. For
      invasive candidiasis, fluconazole is a more convenient option, with the new
      echinocandins or voriconazole as alternatives. CONCLUSIONS: The incidence of
      invasive fungal infection is increasing, but so too are the choices of agents for
      therapy. For reasons of efficacy and safety, therapy with an echinocandin or
      azole antifungal agent is supplanting the use of polyenes.

PMID- 16895518
TI  - Imaging and invasive techniques for diagnosis and treatment of surgical
      infections.
AB  - BACKGROUND: Advances in imaging techniques have caused a radical change in the
      radiologic approach to the diagnosis and treatment of surgical infections.
      METHOD: Review of the pertinent English-language literature. RESULTS:
      Ultrasonography (US) is a useful modality for the initial evaluation of intra
      abdominal infection, whereas computed tomography (CT) often represents the
      modality of choice for definitive identification of the cause and extent of the
      infection. Both US and CT can be used to guide diagnostic fluid aspiration or
      drainage catheter placement. Fluoroscopy may be useful for diagnostic and
      interventional procedures in the biliary and urinary tracts, whereas magnetic
      resonance imaging plays a leading role in evaluating bone and soft tissue
      structures and the pancreatobiliary tree. CONCLUSION: The choice of imaging study
      must be individualized to the particular circumstances of the clinical situation,
      particularly whether image-guided therapy may be required in addition to
      diagnosis. Computed tomography is the most versatile for most clinical
      circumstances.

PMID- 16895519
TI  - Ubiquitin-proteasome degradation of serum- and glucocorticoid-regulated kinase-1
      (SGK-1) is mediated by the chaperone-dependent E3 ligase CHIP.
AB  - SGK-1 (serum- and glucocorticoid-regulated kinase-1) is a stress-induced
      serine/threonine kinase that is phosphorylated and activated downstream of PI3K
      (phosphoinositide 3-kinase). SGK-1 plays a critical role in insulin signalling,
      cation transport and cell survival. SGK-1 mRNA expression is transiently induced
      following cellular stress, and SGK-1 protein levels are tightly regulated by
      rapid proteasomal degradation. In the present study we report that SGK-1 forms a
      complex with the stress-associated E3 ligase CHIP [C-terminus of Hsc (heat-shock
      cognate protein) 70-interacting protein]; CHIP is required for both the ubiquitin
      modification and rapid proteasomal degradation of SGK-1. We also show that CHIP
      co-localizes with SGK-1 at or near the endoplasmic reticulum. CHIP-mediated
      regulation of SGK-1 steady-state levels alters SGK-1 kinase activity. These data
      suggest a model that integrates CHIP function with regulation of the PI3K/SGK-1
      pathway in the stress response.

PMID- 16895520
TI  - Trafficking and phosphorylation dynamics of AQP4 in histamine-treated human
      gastric cells.
AB  - BACKGROUND INFORMATION: AQP4 (aquaporin 4) internalization and a concomitant
      decrease in the osmotic water permeability coefficient (Pf) after histamine
      exposure has been reported in AQP4-transfected gastric HGT1 cells. RESULTS: In
      the present study we report that AQP4 internalization is followed by an increase
      in AQP4 phosphorylation. Histamine treatment for 30 min resulted in an approx. 10
      fold increase in AQP4 phosphorylation that was inhibited by 1 microM H89, a
      specific PKA (protein kinase A) inhibitor, but not by PKC (protein kinase C) and
      CK2 inhibitors. Moreover, measurement of PKA activity after 30 min of histamine
      treatment showed that PKA activity was approx. 3-fold higher compared with basal
      conditions. AQP4 phosphorylation was prevented in cells treated with histamine
      for 30 min after pre-incubation with PAO (phenylarsine oxide), an inhibitor of
      protein endocytosis. Using an endo-exocytosis assay we showed that, after
      histamine washed out, internalized AQP4 recycled back to the cell surface, even
      in cells in which de novo protein synthesis was inhibited by cycloheximide.
      CONCLUSIONS: Phosphorylation experiments, combined with immunolocalization
      studies, indicated that AQP4 phosphorylation is mediated by PKA and occurs
      subsequently to its internalization in late endosomes. We suggest that
      phosphorylation might be a mechanism involved in retaining AQP4 in a vesicle
      recycling compartment.

PMID- 16895521
TI  - Traction forces exerted through N-cadherin contacts.
AB  - BACKGROUND INFORMATION: Mechanical forces play an important role in the
      organization, growth and function of living tissues. The ability of cells to
      transduce mechanical signals is governed by two types of microscale structures:
      focal adhesions, which link cells to the extracellular matrix, and adherens
      junctions, which link adjacent cells through cadherins. Although many studies
      have examined forces induced by focal adhesions, there is little known about the
      role of adherens junctions in force-regulation processes. The present study
      focuses on the determination of force transduction through cadherins at a single
      cell level. RESULTS: We characterized for the first time the distribution of
      forces developed by the cell through cadherin contacts. A N-cadherin (neural
      cadherin)-Fc chimaera, which mimicks the cell adhesion molecule N-cadherin, was
      immobilized on a muFSA (micro-force sensor array), comprising a dense array of
      vertical elastomer pillars, which were used both as a cell culture support for N
      cadherin-expressing C2 myogenic cells and as detectors for force mapping. We
      coated the top of the pillars on which cells adhere and recruit adhesion
      complexes and F-actin. Individual pillar bending allowed the measurement of
      forces that mainly developed at the cell edge and directed toward their centre.
      Similar force distribution and amplitude were detected with an unrelated cell
      line of neuronal origin. Further comparison with forces applied by cells on
      pillars coated with fibronectin indicates that mechanical stresses transduced
      through both types of adhesions were comparable in distribution, orientation and
      amplitude. CONCLUSIONS: These results present a versatile method to measure and
      map forces exerted by cell-cell adhesion complexes. They show that cells
      transduce mechanical stress through cadherin contacts which are of the same order
      as magnitude of those previously characterized for focal adhesions. Altogether,
      they emphasize the mechanotransduction role of cytoskeleton-linked adhesion
      receptors of the cadherin family in tissue cohesion and reshaping.

PMID- 16895522
TI  - Investigation of the mechanism of proton translocation by NADH:ubiquinone
      oxidoreductase (complex I) from bovine heart mitochondria: does the enzyme
      operate by a Q-cycle mechanism?
AB  - Complex I (NADH:ubiquinone oxidoreductase) is the first enzyme of the membrane
      bound electron transport chain in mitochondria. It conserves energy, from the
      reduction of ubiquinone by NADH, as a protonmotive force across the inner
      membrane, but the mechanism of energy transduction is not known. The structure of
      the hydrophilic arm of thermophilic complex I supports the idea that proton
      translocation is driven at (or close to) the point of quinone reduction, rather
      than at the point of NADH oxidation, with a chain of iron-sulfur clusters
      transferring electrons between the two active sites. Here, we describe
      experiments to determine whether complex I, isolated from bovine heart
      mitochondria, operates via a Q-cycle mechanism analogous to that observed in the
      cytochrome bc1 complex. No evidence for the 'reductant-induced oxidation' of
      ubiquinol could be detected; therefore no support for a Q-cycle mechanism was
      obtained. Unexpectedly, in the presence of NADH, complex I inhibited by either
      rotenone or piericidin A was found to catalyse the exchange of redox states
      between different quinone and quinol species, providing a possible route for
      future investigations into the mechanism of energy transduction.

PMID- 16895523
TI  - Primary attachment of murine leukaemia virus vector mediated by particle
      associated heparan sulfate proteoglycan.
AB  - Target cell entry of murine leukaemia virus vectors proceeds via primary
      attachment, independent of the viral envelope protein and subsequent envelope
      receptor interaction. Although much attention has been paid to modifying the
      latter for target cell specificity, the initial binding interaction has been
      overlooked, despite its opposing involvement both in providing the virus
      available for receptor binding and in depleting free virus. As a first step
      towards modifying primary attachment, both to provide specificity and to enhance
      vector availability, we sought to determine the nature of this interaction.
      Following an initial screen of GAGs (glycosaminoglycans) for their ability to
      inhibit virus binding and transduction, we have shown that production of virus
      from cells in which GAG sulfation is inhibited, or treatment of virus with
      heparinase III, reduces both particle attachment and infection. Detection in
      purified virus preparations of a neo-epitope generated by heparinase III
      confirmed the presence of virus-associated HSPG [HS (heparan sulfate)
      proteoglycan], acquired from the producer cell. We propose that host-acquired
      cell-surface HSPG (potentially including syndecan-2) provides a means of virus
      attachment to target cells that precedes specific receptor interaction and
      membrane fusion. Inhibition of HS biosynthesis may provide a sufficiently reduced
      background of primary binding such that novel mechanisms of attachment, ideally
      with appropriate target cell specificity, can be introduced.

PMID- 16895525
TI  - Physical exercises and low back pain.

PMID- 16895526
TI  - Measurements and evaluations in low back pain patients.
AB  - With the present review of literature, the authors intended to compare the
      definition terms, selection criteria, and measurement tools or methods used in
      different studies related to chronic low back pain (CLBP) patients. The relevance
      of including all the above information is that any health-care professional can
      use them to evaluate their treatment methods with CLBP patients or use them in
      study designs according to their objectives. These measurements concern pain
      measurements, measures that were used to describe the CLBP pain, questionnaires
      used to measure the CLBP patients' responses to pain, the pain effects on their
      living activities, and also measurements of the physical abilities and functional
      performance. A computerized literature search in English MEDLINE was conducted
      using "low back pain," and "flexibility, "strength,""evaluation,""functional
      level," and "measurements" as search words. Identified abstracts were scanned,
      and useful articles were acquired for further review. Interms of CLBP
      definitions, the authors concluded that is best defined as a lumbar, sacral, or
      lumbosacral spinal pain that is continuous or essentially continuous but low
      level punctuated by exacerbations of pain, each of which is characterized as
      "acute." In order to establish the criteria for selecting participants in a study
      design related to CLBP, pain characteristics and clinical diagnoses have to be
      taken into consideration for obtaining homogeneity of groups. Finally, the
      selection of measurement tools and evaluation methods is related to the study's
      goals, the specialization of the researchers, and their validity.

PMID- 16895527
TI  - Why do idiopathic scoliosis patients participate more in gymnastics?
AB  - The influence of physical and sporting activities (PSA) on idiopathic scoliosis
      (IS) is still obscure. The aim of this study was to investigate whether such an
      influence exists and if so, to determine its characteristics. Two hundred and one
      teenagers with IS and a control group of 192 adolescents completed an
      epidemiological questionnaire. Those practising gymnastics were more numerous in
      the IS group than in the control group. Moreover, the practice of gymnastics was
      chosen before IS was diagnosed. As gymnastic activities are considered neither as
      a therapy nor as a precursor of IS, the distribution observed could be linked to
      a common factor that both increases the likelihood of IS and favors the practice
      of gymnastics. Joint laxity (JL) may be such a common factor, and was therefore
      tested (wrist and middle finger) on 42 girls with IS and 21 girls of a control
      group. IS patients, practising gymnastics or not, showed a higher JL than the
      control group practising gymnastics or not. Furthermore, the groups practising
      gymnastic activities did not show higher JL levels than the other groups.
      Children with a high JL could be drawn toward gymnastics because of their ability
      to adapt to the constraints of this sport. Girls with a high JL may therefore be
      prone to developing IS. The fact that most teenagers with IS practise gymnastics
      could be related to a higher JL.

PMID- 16895524
TI  - Tumour suppressor p53 down-regulates the expression of the human hepatocyte
      nuclear factor 4alpha (HNF4alpha) gene.
AB  - The liver is exposed to a wide variety of toxic agents, many of which damage DNA
      and result in increased levels of the tumour suppressor protein p53. We have
      previously shown that p53 inhibits the transactivation function of HNF
      (hepatocyte nuclear factor) 4alpha1, a nuclear receptor known to be critical for
      early development and liver differentiation. In the present study we demonstrate
      that p53 also down-regulates expression of the human HNF4alpha gene via the
      proximal P1 promoter. Overexpression of wild-type p53 down-regulated endogenous
      levels of both HNF4alpha protein and mRNA in Hep3B cells. This decrease was also
      observed when HepG2 cells were exposed to UV irradiation or doxorubicin, both of
      which increased endogenous p53 protein levels. Ectopically expressed p53, but not
      a mutant p53 defective in DNA binding (R249S), down-regulated HNF4alpha P1
      promoter activity. Chromatin immunoprecipitation also showed that endogenous p53
      bound the HNF4alpha P1 promoter in vivo after doxorubicin treatment. The
      mechanism by which p53 down-regulates the P1 promoter appears to be multifaceted.
      The down-regulation was partially recovered by inhibition of HDAC activity and
      appears to involve the positive regulator HNF6alpha. p53 bound HNF6alpha in vivo
      and in vitro and prevented HNF6alpha from binding DNA in vitro. p53 also
      repressed stimulation of the P1 promoter by HNF6alpha in vivo. However, since the
      R249S p53 mutant also bound HNF6alpha, binding HNF6alpha is apparently not
      sufficient for the repression. Implications of the p53-mediated repression of
      HNF4alpha expression in response to cellular stress are discussed.

PMID- 16895528
TI  - The predictive value of exercise testing for survival among 75-year-old men and
      women.
AB  - All 75-year-olds born in 1914 and living in the city of Jyvaskyla, central
      Finland (n=388) were invited to study the predictive value of exercise test for
      mortality. Subjects who entered the laboratory (n=295) were to have a standard
      pre-test evaluation and perform a cycle ergometer exercise test. Subjects with
      complete background, exercise-test status and mortality data (n=282) were divided
      into three groups according to exercise-test status: a non-exercise test group
      (n=79), an exercise-test termination group (n=95), and an exercise-test
      completion group (n=108). Mortality was followed up for 9 years. The multivariate
      hazard ratio (HR) for death among the non-exercise test group compared with
      exercise-test completion group was 1.87 (CI 1.19-2.94). The multivariate HR for
      death among the exercise-test termination group compared with the exercise-test
      completion group was 0.95 (CI 0.58-1.54). High cycling power (W/kg body weight)
      in the exercise-test completion group was associated with a decreased risk for
      death with a multivariate HR 0.14 (CI 0.05-0.38). Performing an exercise test
      serves information on the risk of death that is incremental to clinical data and
      traditional risk factors of death in elderly people.

PMID- 16895529
TI  - Functional ability at age 75: is there an impact of physical inactivity from
      middle age to early old age?
AB  - The aim of this study is to analyze the impact of physical inactivity from middle
      age to early old age on functional ability at age 75. Physical activity is
      measured both as cumulated activity from age 50 to 60 to 70 and at three separate
      points in time. Three hundred eighty-seven men and women born in 1914 and living
      in seven municipalities in the western part of the County of Copenhagen were
      followed for 25 years with examinations in 1964, 1974, 1984 and 1989. Analyses
      were conducted with physical inactivity as an independent variable (accumulated
      and separately for each point in time) and smoking, sex, school education,
      household composition, chronic disease at baseline and functional ability at age
      70 as possible confounders. There was a strong association between physical
      inactivity at age 70 and disability at age 75. However, the analyses showed no
      effect of cumulated physical inactivity from age 50 to 60 to 70 on disability at
      age 75 when adjusting for functional ability at age 70. Physical inactivity is a
      risk factor for disability among old people. Thus, old people should be
      encouraged to take up and maintain physical training throughout the aging
      process.

PMID- 16895530
TI  - Daily physical activity in Swedish children aged 8-11 years.
AB  - INTRODUCTION: Physical inactivity is hypothesized to be a contributing factor in
      the development of a variety of diseases. Recommendations for an adequate level
      of physical activity have been proposed. There are few studies in which the
      physical activity in children has been objectively assessed. The purpose of this
      study was to estimate objectively the level of physical activity in Swedish
      children. MATERIALS AND METHODS: We studied 248 children (140 boys and 108 girls)
      aged 7.9-11.1 years from Malmo, Sweden. Physical activity was measured with
      accelerometers. Children were instructed to wear the accelerometers for 4 days.
      The mean daily activity was expressed as the mean counts per minute of recording.
      The time that the child spent performing moderate or vigorous activity was
      calculated by using previously established cutoff points. RESULTS: The mean daily
      activity was higher in boys than in girls, 751+/-243 vs 618+/-154 counts/min
      (P<0.001). All children fulfilled the recommendation for moderate physical
      activity for 60 min or more per day. Ninety-two percent of the boys and 86% of
      the girls performed vigorous activity, for 20 min or more per day. CONCLUSION:
      All children, aged 8-11 years, who participated in this study reached the
      recommended level of physical activity, with boys being more active than girls.

PMID- 16895532
TI  - Neuromuscular fatigue and recovery in elite female handball players.
AB  - The purpose of this study was to investigate the degree of neuromuscular fatigue
      and recovery from fatigue, following handball training and handball matches at
      elite level. The focus was specifically on changes in physical performance when
      playing three matches over the course of 3 days, which simulates a sequence in
      international championships. Female players from the Norwegian national handball
      team were tested during a 5-day training camp (seven players) and a 3-day
      international tournament (eight players). Testing was done before and after
      training sessions and matches. Neuromuscular fatigue was measured as changes in
      voluntary isokinetic knee extensions, jump height in counter-movement jumps, and
      20 m sprint time. The results showed a significant reduction by 2-6% in all three
      performance tests during the training camp and by 4-7% during the tournament
      (sprint and jump test) (P<0.05). Slow recovery was indicated by incomplete
      restoration of performance between matches and training sessions. The paper
      discusses the insufficient recovery measured related to handball performance.
      Because of changes in the rules of the game and strategic tendencies towards
      higher speed in play, the physical demands in elite handball seems to be
      increasing. The results of the study indicate that coaches should consider
      physical loading and recovery time available when distributing playing time
      between individual players in international tournaments.

PMID- 16895533
TI  - Voluntary activation and central activation failure in the knee extensors in
      young women and men.
AB  - Quadriceps muscle weakness is common after knee injuries. This weakness is
      caused, in part, by reduced voluntary activation (VA) because of central
      activation failure (CAF). Superimposed electrical stimulation techniques are used
      to assess VA and to detect CAF. The aim of this study was to assess VA during
      knee extension in young healthy women and men, and to evaluate subjective
      discomfort from the electrical stimulation. The quadriceps muscle in six young
      healthy women (mean age 22 years) and six young healthy men (mean age 29 years)
      was stimulated during maximal voluntary contractions using a 100 Hz pulse train.
      Data were collected from two test sessions separated by 6-8 days and each session
      comprised of two trials. A visual analog scale for pain (VAS-pain) was used to
      evaluate subjective discomfort. Overall, young healthy, moderately active men and
      women did have the ability to fully activate their knee extensors isometrically,
      but they did not achieve full activation on every trial. In those trials where a
      CAF was detected, the degree was small (mean less than 2%), and did not vary
      between the two test sessions. Subjective discomfort was generally moderate and
      tolerable (mean VAS-pain score 35 mm). These results will assist the clinical
      assessment of muscle weakness following a knee injury and facilitate the design
      and evaluation of appropriate rehabilitation interventions.

PMID- 16895531
TI  - Physical activity, body composition and physical self-esteem: a 3-year follow-up
      study among adolescents in Sweden.
AB  - AIMS: To measure physical activity by means of daily pedometer steps, body
      composition, expressed as body mass index (BMI) and bioelectrical impedance as
      percent body fat, and perceived physical self-esteem and additionally, to
      evaluate eventual predictors for a healthy lifestyle i.e., highly physically
      active, normal weighted and a high physical self-esteem in a follow-up group.
      METHODS: During autumn 2000 physical activity level was assessed and BMI was
      calculated in 871 children aged 7-14 in south eastern Sweden and in 501 of these,
      physical self-esteem were also assessed. During autumn 2003 a total of 375
      adolescents aged 15-18 were assessed using the same methodology and additionally
      percent body fat was measured. Ninety-three of these adolescents (46 girls), were
      also measured in 2000 and they formed the follow-up group. RESULTS: In the follow
      up group a significant increase in BMI and stability in physical self-esteem in
      boys and girls, and in boys a significant decrease in daily steps was found 3
      years later. Strongest predictor to be highly physically active, maintain normal
      BMI and high self-esteem 3 years later, i.e., to have a healthy lifestyle, was
      for girls increased self-esteem and for boys a decreased BMI. CONCLUSION:
      Consequently, for a healthy lifestyle, promoting physical self-esteem in girls
      and weight control in boys is of great importance in early adolescence.

PMID- 16895534
TI  - Evaluation of Tc-99m-tetrofosmin single-photon emission computed tomography for
      detection of chronic exertional compartment syndrome of the leg.
AB  - Chronic exertional compartment syndrome (CECS) of the leg is a common, painful
      condition related to exercise and associated with increased muscle compartment
      pressure (CP). Invasive methods are currently the method of choice for diagnosing
      the condition. We investigated the use of Tc-99m-tetrofosmin perfusion single
      photon emission computed tomography (SPECT) as a diagnostic tool compared with
      the gold standard, muscle CP measurement. In 14 subjects perfusion SPECT and CP
      were measured before and immediately after exercise leading to pain in the lower
      legs. Six subjects had increased pressures indicating the presence of CECS. In
      three (50%) of these muscular hypoperfusion was observed by perfusion SPECT. In
      eight subjects with normal CPs SPECT suggested muscular hypoperfusion. Because of
      the low diagnostic rates, sensitivity 50% and specificity 63%, Tc-99m-tetrofosmin
      perfusion SPECT seems not to be a useful method for diagnosing CECS.

PMID- 16895535
TI  - Infectious episodes before and after a marathon race.
AB  - The aim of this study was to investigate the incidence of self-reported
      infectious episodes (IE) during 3 weeks before (pre-IE) and 3 weeks after (post
      IE) a marathon race and relate these figures to training status, running time,
      socioeconomic and demographic factors. Two questionnaires, including questions
      about important factors for IE incidence, were given to a representative cohort
      of 1694 runners (17% of all finishers) in the Stockholm Marathon 2000. Pre-IE
      incidence in the cohort was 17% with no difference between women and men. Post-IE
      incidence in the whole cohort was 19% with no significant (P>0.05) difference
      between women and men. The post-IE incidence in runners without a pre-IE was 16%
      (P>0.05 to pre-IE incidence). In the group of runners with pre-IE, 33%
      experienced an IE after the race also (P<0.05 to Pre-IE incidence). A logistic
      regression analysis showed that younger age and pre race health status and, for
      men only, experienced nausea during and after the race were depended factors
      explaining post-IE incidence. Younger runners were more prone to experience IE
      both before and after the race. There was no relation between training volume 6
      months before the race, finishing time and socioeconomic and demographic factors
      and pre-IE or post-IE. This study does not support the theory of increased
      infection rate after exhaustive long-distance running ("The Open Window Theory")
      in recreational runners, but suggests that the sometimes experienced increased
      rate of infections among athletes can be caused by strenuous exercise too soon
      after an infection.

PMID- 16895537
TI  - Cerebrovascular dysfunction is an attractive target for therapy in heat stroke.
AB  - 1. The aim of the present review is to summarize clinical observations and
      results of animal models that advance the knowledge of the attenuation of
      cerebrovascular dysfunction in the setting of heat stroke. It is a narrative
      review of selected published literature from Medline over the period 1959-2005.
      2. All heat-stressed rodents, even under general anaesthesia, have hyperthermia,
      systemic inflammation, hypercoagulable state, arterial hypotension and tissue
      ischaemia and injury in multiple organs. These findings demonstrate that rodent
      heat stroke models can nearly mirror the full spectrum of human heat stroke.
      Experimental heat stroke fulfills the empirical triad used for the diagnosis of
      classical human heat stroke, namely hyperthermia, central nervous system
      alterations and a history of heat stress. 3. These physiological dysfunctions and
      survival during heat stroke can be improved by whole-body or brain cooling
      therapy adopted immediately after the onset of heat stroke. 4. However, in the
      absence of body or brain cooling, these heat stroke reactions can still be
      reduced by the following measures: (i) fluid replacement with 3% NaCl solution,
      10% human albumin or hydroxyethyl starch; (ii) intravenous delivery of anti
      inflammatory drugs, free radical scavengers or interleukin-1 receptor
      antagonists; (iii) hyperbaric oxygen therapy; or (iv) transplantation of human
      umbilical cord blood cells. 5. In addition, before initiation of heat stress,
      prior manipulations with one of the following measures was found to be able to
      protect against heat stroke reactions: (i) systemic delivery of alpha-tocopherol,
      mannitol, inducible nitric oxide synthase inhibitors, mu-opioid receptor
      antagonists, endothelin ETA receptor antagonists, serotoninergic nerve depletors
      or receptor antagonists, or glutamate receptor antagonists; or (ii) heat shock
      protein 72 preconditioning. 6. There is compelling evidence that cerebrovascular
      dysfunction is an attractive target for therapy in heat stroke.

PMID- 16895538
TI  - Chronic fluvastatin treatment alters vascular contraction by inhibiting the
      Rho/Rho-kinase pathway.
AB  - 1. In the present study, we investigated the effects of chronic treatment of
      stroke-prone spontaneously hypertensive rats (SHRSP) with the statin fluvastatin
      on vascular Rho/Rho-kinase pathway mediated contraction, which has been shown to
      be upregulated in hypertension. 2. Contribution of the Rho/Rho-kinase pathway to
      noradrenaline-induced contraction of arteries from SHRSP was assessed by the
      inhibitory effect of Y-27632, a Rho/Rho-kinase inhibitor. Stroke-prone
      spontaneously hypertensive rats were treated with fluvastatin (10 mg/kg per day)
      for 1 month. 3. Treatment with fluvastatin tended to attenuate the contraction to
      noradrenaline and significantly decreased the Y-27632-sensitive component of the
      contraction in controls compared with fluvastatin-treated rats. 4. RhoA, as
      assessed by western blotting, was also reduced by fluvastatin treatment. 5. These
      findings suggest that chronic treatment with fluvastatin reduces the contractile
      response associated with Rho/Rho-kinase in arteries of hypertensive rats.

PMID- 16895539
TI  - Resetting of aortic baroreceptors in response to hypotension does not alter gain
      sensitivity.
AB  - 1. In chronic hypertension, the baroreceptors reset to hypertensive levels with a
      decrease in gain sensitivity, but only a few studies have evaluated baroreceptor
      resetting during chronic hypotension and, under these conditions, no consistent
      information is available concerning changes in baroreceptor gain sensitivity.
      Therefore, in the present study, the aortic baroreceptor function curve and the
      baroreflex control of heart rate (HR) were evaluated in chronic hypotension
      produced by myocardial infarction (MI) with no heart failure. 2. Aortic
      baroreceptor function curves were studied in anaesthetized three groups of rats:
      (i) MI-7, six rats 7 days after MI; (ii) MI-30, nine rats 30 days after MI; and
      (iii) five control animals (SHAM). The pressure-nerve activity relationship was
      measured during rapid changes in blood pressure by integrating the whole-nerve
      activity of the baroreceptors in a computerized beat-to-beat analysis. 3. Both
      long-term periods (7 or 30 days) of hypotension were accompanied by complete
      resetting of the baroreceptor in rats (the leftward displacement of the
      baroreceptor curve matched the decrease in blood pressure). Moreover, the
      resetting of the baroreceptor function curve was not accompanied by changes in
      gain sensitivity (1.47, 1.64 and 1.67%/mmHg for SHAM, MI-7 and MI-30 groups,
      respectively) and the baroreflex control of HR was normal comparing SHAM and MI
      30 groups (bradycardic 1.62 +/- 0.18 vs 1.99 +/- 0.52 b.p.m./mmHg, respectively;
      tachycardic 3.6 +/- 0.5 vs 4.1 +/- 0.4 b.p.m./mmHg for, respectively). 4. The
      data indicate that the resetting of baroreceptors in chronic hypotension is
      stable and is not accompanied by changes in gain sensitivity, as observed in
      hypertension. This may account for the normal baroreflex control of HR observed
      in non-anaesthetized rats.

PMID- 16895540
TI  - Alteration of fexofenadine disposition in the rat isolated perfused liver
      following injection of bacterial lipopolysaccharide.
AB  - 1. The aim of the present study was to examine the effect of bacterial
      lipopolysaccharide (LPS) on the disposition of an organic anion transporting
      polypeptide and P-glycoprotein substrate in the rat isolated perfused liver. 2.
      Male Sprague-Dawley rats were divided into four groups. Three of the groups
      received 1, 2.5 or 5 mg/kg, i.p., Escherichia coli LPS in sterile saline. The
      fourth group received an equivalent volume of sterile saline i.p. Twenty-four
      hours after treatment, rats were anaesthetized and the liver isolated and
      perfused with fexofenadine at an initial concentration of 2000 ng/mL in a
      recirculating system. Perfusate and bile samples were collected for 60 min and
      the liver was collected at the end of the perfusion. Fexofenadine concentrations
      were determined by HPLC. Fexofenadine pharmacokinetic parameters, the final liver
      : perfusate (L : P) and bile : liver (B : L) concentration ratios were
      determined. 3. Injection of LPS changed the hepatic disposition of fexofenadine.
      The changes were most marked in the 5 mg/kg LPS group. Notably, clearance from
      the perfusate (CL) and into the bile (CLB; 5.9 +/- 0.6 and 1.24 +/- 0.20 mL/min,
      respectively), L : P (44 +/- 11) and B : L (17 +/- 2) were all reduced (P < 0.05)
      in this group compared with control (CL 10.0 +/- 1.1 mL/min; CLB 2.7 +/- 0.5
      mL/min; L : P 87 +/- 14; and B : L 30 +/- 4). 4. In conclusion CL and CLB were
      reduced following treatment with LPS in a manner consistent with downregulation
      of both canalicular and sinusoidal transport.

PMID- 16895541
TI  - Upregulation of angiotensin AT1 receptor and intracellular kinase gene expression
      in hypertensive rats.
AB  - 1. Activation of angiotensin II AT1 receptors (AT1R) stimulates catecholamine
      systems within both central and peripheral tissues that are associated with blood
      pressure control. In the present study, we sought to determine whether the
      hypertensive phenotype of the spontaneously hypertensive rat (SHR) is associated
      with changes in AT1R gene expression and whether gene expression of downstream
      signalling molecules was coupled to catecholamine gene expression, both in key
      brainstem nuclei and in peripheral sites implicated in cardiovascular control. 2.
      Gene expression levels of AT1R, extracellular signal-regulated kinase (ERK) 1 and
      2 and phosphatidylinositol 3-kinase (PI3-K) were quantified in Wistar-Kyoto (WKY)
      rats and SHR. Messenger RNA expression levels were quantified using real time
      reverse transcription-polymerase chain reaction. In addition, we investigated
      whether there was a relationship between gene expression and systolic blood
      pressure. 3. The gene expression levels of AT1R, ERK2 and PI3-K were
      significantly higher in the paraventricular nucleus of the hypothalamus (4.12-,
      1.40- and 1.38-fold, respectively), rostral ventrolateral medulla (2.71-, 1.33-
      and 2.73-fold, respectively), spinal cord (30.5-, 2.72- and 1.53-fold,
      respectively), adrenal medulla (1.68-, 1.55- and 1.76-fold, respectively) and
      coeliac ganglion (1.39-, 1.35- and 1.12-fold, respectively) in SHR compared with
      WKY rats. There was no significant difference in the level of ERK1 gene
      expression between the two strains. The gene expression levels of AT1R and ERK2
      were positively correlated with blood pressure in all central nervous tissues
      investigated in the SHR, but not in WKY rats. Gene expression levels of the AT1R
      in the coeliac ganglion and adrenal medulla were also positively correlated with
      increased systolic blood pressure. 4. The present data suggest that a defect in
      AT1R expression (that may further alter downstream signalling pathways) in the
      SHR may be responsible, at least in part, for the hypertensive phenotype.

PMID- 16895542
TI  - Growth inhibition of mesenchymal stem cells by aspirin: involvement of the
      WNT/beta-catenin signal pathway.
AB  - 1. Mesenchymal stem cell (MSC) therapy is drawing increasing attention in
      cardiology. However, the effect of aspirin, an assistant medication used
      extensively in the treatment of cardiovascular diseases, on MSC is not clear. 2.
      In the present study, we investigated the effect of aspirin on the growth of MSC
      in vitro and the underlying mechanism of its action. 3. The 3-(4,5-dimethyl-2
      thiazoyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay revealed that 1, 5 and
      10 mmol/L aspirin inhibited the growth of MSC by 18, 37 and 62%, respectively.
      DNA synthesis of MSC was inhibited by 25, 57 and 90% following treatment with 1,
      5 and 10 mmol/L aspirin, respectively, as determined by the tritiated thymidine
      incorporation assay. No cytotoxicity was observed based on Trypan blue dye
      exclusion and cell morphological observations. Western blot analysis demonstrated
      that the protein level of phosphorylated beta-catenin increased, whereas that of
      cyclin D1 decreased, after treatment of MSC with aspirin. Cell cycle analysis
      showed that aspirin failed to significantly alter the proportion of cells in
      different stages of the cell cycle. 4. These observations indicate that aspirin
      inhibits MSC proliferation and that the downregulation of the wnt/beta-catenin
      signal pathway may be involved in the growth inhibition of MSC by aspirin.

PMID- 16895543
TI  - Characterization of cationic amino acid transport systems in rat erythrocytes:
      lack of effect of uraemia on L-arginine influx.
AB  - 1. Chronic renal failure (CRF) is associated with the abnormal regulation of
      nitric oxide (NO) synthesis at the systemic level. The transport of L-arginine,
      upregulated in blood cells from uraemic patients, modulates NO synthesis in this
      pathological condition. The model of partial nephrectomy in rats is widely
      accepted as a valid model of uraemia. Because there are no reports of L-arginine
      transport in blood cells from uraemic rats, the aim of the present study was to
      investigate L-arginine transport in red blood cells (RBCs) from these rats. 2.
      The kinetics of L-arginine transport in RBC and plasma and the amino acid
      profiles of RBC were investigated in control, sham-operated and subtotally
      nephrectomized rats. 3. L-Arginine transport was mediated via the cationic amino
      acid transport system y+ and a transport system with kinetics resembling the
      human system y+L. In control RBC, the apparent Ki for L-leucine inhibition of L
      arginine transport via system y+L was 0.16 +/- 0.02 and 4.8 +/- 2 mmol/L in the
      presence of Li+ and Na+, respectively. 4. The Vmax values for L-arginine
      transport via system y+L and system y+ were similar in RBC from control sham
      operated and uraemic rats. Moreover, L-arginine concentrations in plasma and RBC
      were not affected by uraemia. 5. The findings of the present study provide the
      first evidence that L-arginine transport in rat erythrocytes is mediated by two
      distinct cationic transport systems with characteristics of systems y+ and y+L,
      which accept neutral amino acids only in the presence of Li+. In contrast with
      previous studies in uraemic patients, plasma levels and maximal transport rates
      of L-arginine were not altered in this rat model of CRF.

PMID- 16895544
TI  - High-fat feeding reduces endothelium-dependent vasodilation in rats: differential
      mechanisms for saturated and unsaturated fatty acids?
AB  - 1. Chronic feeding with a high-fat diet can cause metabolic syndrome in rodents
      similar to humans, but the role of saturated versus unsaturated fats in vascular
      tension remains unclear. 2. The present study shows that rats on a diet rich in
      either saturated or unsaturated fat had higher blood pressure compared with chow
      fed rats (approximately 130 vs 100 mmHg, respectively), along with
      hyperlipidaemia and insulin resistance. Compared with responses of phenylephrine
      preconstricted artery segments from chow-fed rats, vasorelaxation of isolated
      renal arteries from high-fat fed rats was reduced substantially (> 50%) in
      response to acetylcholine (0.01-10 micromol/L) and moderately to nitroprusside
      (>or=1 micromol/L) at low concentrations. Acetylcholine-induced vasorelaxation of
      arteries from high-fat fed rats was also more sensitive to inhibition by the
      nitric oxide (NO) synthase inhibitors NG-nitro-L-arginine and methylene blue. 3.
      In human umbilical vein endothelial cells, the production of NO and endothelin-1
      was significantly inhibited by unsaturated fatty acids. In comparison, saturated
      fatty acids stimulated endothelin-1 production without altering NO production. 4.
      The data indicate that both saturated and unsaturated high-fat feeding may result
      in an increase in blood pressure owing to reduced endothelium-dependent
      vasorelaxation in the arterial system. The impaired endothelium-dependent
      vasorelaxation induced by saturated and unsaturated fatty acids may involve
      different mechanisms.

PMID- 16895545
TI  - Effect of perinatal hypoxia on cardiac tolerance to acute ischaemia in adult male
      and female rats.
AB  - 1. The number of adult patients undergoing surgery for congenital cyanotic
      defects in childhood has increased significantly. Therefore, the aim of the
      present study was to examine the effect of perinatal hypoxia on the tolerance of
      the adult myocardium to acute ischaemia-reperfusion injury. 2. Pregnant Wistar
      rats were exposed to intermittent hypobaric hypoxia 7 days before delivery; pups
      were born under normoxic conditions and exposed to hypoxia again for 10 postnatal
      days. After the last hypoxic exposure, all animals were kept for an additional 3
      months under normoxic conditions. All experiments were performed on 90-day-old
      rats. 3. Ventricular arrhythmias were assessed on isolated perfused hearts during
      30 min occlusion of the left anterior descending coronary artery. Infarct size
      was measured on isolated hearts (40 min regional ischaemia and 120 min
      reperfusion) and on open-chest animals (20 min regional ischaemia and 3 h
      reperfusion). 4. Perinatal exposure to hypoxia significantly increased cardiac
      tolerance to ischaemic injury in adult females, as evidenced by the lower
      incidence and severity of ischaemic ventricular arrhythmias, compared with the
      normoxic group. The effect of perinatal hypoxia on ischaemic arrhythmias in males
      was quite the opposite. Myocardial infarct size measured in open-chest animals
      only was significantly smaller in normoxic females compared with normoxic males.
      Perinatal exposure to hypoxia had no effect on infarct size in either setting or
      sex. 5. The results of the present study support the hypothesis that perinatal
      hypoxia is a primary programming stimulus in the heart that may lead to sex
      dependent changes in cardiac tolerance to acute ischaemia in later adult life.
      This would have important implications for patients who have experienced
      prolonged hypoxaemia in early life.

PMID- 16895546
TI  - Mechanisms underlying nebivolol-induced endothelial nitric oxide synthase
      activation in human umbilical vein endothelial cells.
AB  - 1. Nebivolol (NEB) has been shown to be a selective blocker of beta1
      adrenoceptors with additional vasodilating properties that are mediated, at least
      in part, by an endothelial-dependent liberation of nitric oxide (NO). In the
      present study, we investigated the underlying mechanisms of NEB-induced
      vasodilation. 2. Immunohistochemical staining of endothelial nitric oxide
      synthase (eNOS) was performed in the absence and presence of NEB in human
      umbilical vein endothelial cells (HUVEC). In addition, we measured the release of
      nitric oxide (NO) using diaminofluorescein. Metoprolol (MET) was used for
      comparison. 3. Nebivolol, but not MET (each at 10 micromol/L), caused a time
      dependent increase in NO release from HUVEC, as demonstrated by an increase in
      DAF fluorescence at 0 versus 10 min (+234 +/- 7 and 55 +/- 22% basal,
      respectively). Blockade of beta3-adrenoceptors by SR 59230A (1 micromol/L)
      partially reduced the NEB-induced increase in DAF fluorescence. Complete
      inhibition of NEB-induced NO liberation was achieved by the simultaneous blockade
      of beta3-adrenoceptors and oestrogen receptors (with 1 micromol/L ICI 182,780).
      4. Application of NEB significantly increased eNOS translocation and serine 1177
      phosphorylation of eNOS. However, NEB did not alter eNOS-phosphorylation at
      threonine 495 and at serine 114. 5. In conclusion, the endothelium-dependent NO
      liberation induced by NEB is due to stimulation of beta3-adrenoceptors and
      oestrogen receptors and coincides with eNOS translocation and a phosphorylation
      at eNOS-serine 1177. These characteristics of NEB may be beneficial not only when
      treating patients suffering from cardiovascular disease, but may also prevent
      further deterioration of endothelial dysfunction.

PMID- 16895548
TI  - Behaviour of the anti-oxidant defence system and heme oxygenase-1 protein
      expression in fructose-hypertensive rats.
AB  - 1. Addition of fructose to a rat diet for various periods of time leads to
      hypertension, hyperinsulinaemia and dyslipidaemia and provides a model for
      testing oxidative stress parameters in the animals. 2. In the present study,
      oxidative stress generation, the soluble and enzymatic defence system and heme
      oxygenase-1 (HO-1) protein expression were investigated in the heart, liver and
      kidney of rats fed fructose for a period of 1 or 8 months. 3. Compared with the
      control group, fructose-hypertensive rats showed increased in lipid peroxidation
      only in the heart after both 1 and 8 months of fructose treatment. Changes in the
      behaviour of the soluble and enzymatic defence system and HO-1 protein expression
      were different depending on the organ. Increased or unaltered activities of anti
      oxidant enzymes were found in the liver and kidney, respectively. Induction of HO
      1 prevented the generation of oxidative stress in the liver, where the activity
      of anti-oxidant defence enzymes was not reduced. Increased expression of HO-1
      protein was not able to prevent the generation of oxidative stress in the heart,
      where fructose treatment diminished the activity of anti-oxidant enzymes. 4. The
      results of the present study demonstrate that upregulation of HO-1 may prevent
      the generation of oxidative stress only when the anti-oxidant defence system is
      still operative.

PMID- 16895547
TI  - Carnitine esters prevent oxidative stress damage and energy depletion following
      transient forebrain ischaemia in the rat hippocampus.
AB  - 1. The present study investigated whether propionyl-L-carnitine (PLC) has
      neuroprotective effects, similar to those reported for acetyl-L-carnitine (AC),
      against transient forebrain ischaemia-induced neuronal damage and biochemical
      derangement in the rat hippocampal CA1 region. 2. In total, 105 adult male Wistar
      albino rats were divided into seven groups of 15 animals each. The first three
      groups were injected i.p. with normal saline, AC (300 mg/kg) or PLC (300 mg/kg)
      for 7 successive days. The next three groups were injected i.p. with the same
      doses of normal saline, AC or PLC immediately after the induction of 10 min
      forebrain ischaemia and i.p. injections were continued for 7 successive days.
      Rats in the seventh group were subjected to sham-operated ischaemia and injected
      with normal saline for 7 successive days. 3. Seven days after treatment, animals
      were killed and their brains isolated for histopathological examination and
      biochemical studies. 4. Forebrain ischaemia resulted in a significant decrease in
      the number of intact neurons (77%), ATP concentration (51%) and glutathione
      content (32%), whereas there was a significant increase in the production of
      thiobarbituric acid-reactive substances (TBARS; 71%) and total nitrate/nitrite
      (NOx; 260%) in hippocampal tissues. 5. Administration of either AC or PLC
      attenuated forebrain ischaemia-induced neuronal damage, manifested by a greater
      number of intact neurons, ATP and glutathione, as well as a decrease in TBARS and
      NOx in hippocampal tissues. 6. Results from the present study suggest, for the
      first time, that PLC attenuates forebrain ischaemia-induced neuronal injury,
      oxidative stress and energy depletion in the hippocampal CA1 region. Propionyl-L
      carnitine has neuroprotective effects similar to AC and could have a potential
      use in the treatment of neurodegenerative diseases. 7. The results of the present
      study will open up new perspectives for the use of PLC in the treatment of
      neurodegenerative diseases associated with, or secondary to, myocardial ischaemia
      reperfusion injury and chronic circulatory failure.

PMID- 16895549
TI  - Are gap junctions truly involved in inhibitory neuromuscular interaction in mouse
      proximal colon?
AB  - 1. Gap junctions exist between circular muscle cells of the colon and between
      interstitial cells of Cajal (ICC) in the myenteric plexus of the gastrointestinal
      tract. They also probably couple intramuscular ICC with smooth muscle cells.
      Recent functional evidence for this was found in dye-coupling and myoelectrical
      experiments. 2. In the present study, we tested the hypothesis of gap junctions
      putatively being involved in neuromuscular interaction in mouse colon by using
      different classes of gap junction blockers. 3. Electrical field stimulation of
      the myenteric plexus elicited tetrodotoxin-sensitive and hexamethonium
      independent fast and slow inhibitory junction potentials (fIJP and sIJP,
      respectively) in circular smooth muscle cells, as evaluated by intracellular
      recording techniques in impaled smooth muscle cells. Heptanol produced a time
      dependent hyperpolarization of the membrane potential (MP) and abolished fIJP and
      sIJP. Octanol had no effect on the MP and abolished fIJP and sIJP. Carbenoxolone
      produced a time-dependent depolarization of the MP without any effect on fIJP or
      sIJP. The connexin 43 mimetic gap junction blocker GAP-27 had no effect on MP,
      fIJP or sIJP. 4. Based on the presently available gap junction blockers we found
      no evidence that gap junctions are involved in neuromuscular transmission in
      mouse colon, as suggested by morphological studies.

PMID- 16895550
TI  - Beta-adrenoceptor-mediated inhibition of mediator release from human peripheral
      blood-derived mast cells.
AB  - 1. Mast cells cultured from human peripheral blood have been used as a cell model
      for functional studies of human mast cells, particularly human lung mast cells.
      However, the beta-adrenoceptor subtype expressed by these cultured cells has not
      been identified. The aim of the present study was to characterize
      pharmacologically the beta-adrenoceptors involved in the suppression of IgE
      mediated release of mediators, including histamine, prostaglandin (PG) D2 and
      leukotriene (LT) C4 from cultured mast cells. 2. Mast cells were cultured from
      mast cell progenitors isolated from peripheral blood in the presence of 200 ng/mL
      stem cell factor and 50 ng/mL interleukin-6. Mast cells were sensitized with
      human myeloma IgE, treated with beta-adrenoceptor agonists or antagonist and then
      challenged with anti-human IgE. The release of histamine, PGD2 and LTC4 from mast
      cells was determined. 3. Both isoprenaline and salbutamol inhibited anti-IgE
      induced release of histamine, PGD2 and LTC4 from cultured mast cells in a dose
      dependent manner. Isoprenaline was a more potent inhibitor than salbutamol. The
      pD2 values for the inhibition of the release of histamine, PGD2 and LTC4 were
      7.37 +/- 0.12, 8.38 +/- 0.23, 8.85 +/- 0.23, respectively, for isoprenaline and
      6.96 +/- 0.12, 7.65 +/- 0.36, 7.91 +/- 0.64, respectively, for salbutamol. The
      selective beta3-adrenoceptor agonist BRL-37344 failed to affect anti-IgE-induced
      histamine release from cultured mast cells. 4. The selective beta2-adrenoceptor
      antagonist ICI 118 551 (108 mol/L) strongly reversed the concentration-dependent
      suppression of histamine release by isoprenaline and salbutamol; however, the
      selective beta1-adrenoceptor antagonist atenolol (106 mol/L) did not have any
      effect. 5. These results indicate that both isoprenaline and salbutamol act at
      beta2-adrenoceptors to suppress IgE-mediated mediator release from cultured human
      mast cells.

PMID- 16895551
TI  - Effects of perindopril and hydrochlorothiazide on selected indices of oxidative
      stress in the blood of elderly patients with essential hypertension.
AB  - 1. The aim of the present study was to determine the effect of hypotensive
      therapy with a diuretic (hydrochlorothiazide) and an angiotensin-converting
      enzyme inhibitor (perindopril) on selected oxidative stress parameters in the
      blood of elderly patients with essential hypertension. 2. Studies were performed
      in 45 elderly patients with essential hypertension at baseline and after the 45th
      day of perindopril (n = 25) or hydrochlorothiazide (n = 20) therapy, as well as
      in 25 young and 25 elderly normotensive subjects. The following parameters were
      measured: systolic and diastolic blood pressure, nitric oxide (NO), carbonyl
      groups and malondialdehyde (MDA) concentrations, as well as the activity of
      ceruloplasmin (Cp) oxidase, Cu-Zn superoxide dismutase (SOD-1) and catalase
      (CAT). 3. The activity of SOD-1 and NO levels were reduced with age. 4. Compared
      with elderly controls, hypertensive subjects showed increases in baseline MDA,
      carbonyl group concentrations and Cp oxidase activity and decreases in NO levels
      and SOD-1 and CAT activities. 5. Treatment with perindopril, but not
      hydrochlorothiazide, resulted in significant increases in SOD-1 and CAT
      activities and decreases in MDA concentration and Cp oxidase activity. Both
      therapies decreased the level of carbonyl groups and increased NO levels. 6.
      Angiotensin-converting enzyme inhibitor therapy has significant anti-oxidant
      effects that may be important in the treatment of elderly patients with essential
      hypertension.

PMID- 16895552
TI  - Reduced sinoatrial cAMP content plays a role in postnatal heart rate slowing in
      the rabbit.
AB  - 1. Decreasing heart rate during development is known to be the result of
      parasympathetic nervous system maturation that depresses the pacemaker current
      (If) by acetylcholine (ACh). However, a direct effect of ACh on If has been ruled
      out and the involvement of other secondary messengers, such as cAMP, was verified
      in previous studies. Therefore, we hypothesized that reduced basal cAMP
      production in sinoatrial (SA) nodal cells may contribute to the slowing of heart
      rate after birth. 2. The electrocardiogram and heart rate variability (HRV) were
      documented and measured in vivo and in vitro (in isolated perfused Langendorff
      preparations) for rabbits aged 2, 4, 6, 8 and 12 weeks. Sinoatrial node action
      potential (AP) recording and perforated patch-clamp analyses were used to
      investigate the spontaneous depolarization rate and pacemaker If currents.
      Concentrations of cAMP in SA nodal tissues were determined by radioimmunoassay.
      Relative expression of adenylate cyclases (ADCY1, 5) and phosphodiesterases
      (PDE1A, 4A and 8A) were quantified by real-time reverse transcription-polymerase
      chain reaction. 3. Significantly reduced heart rate, but unchanged HRV, was
      observed in perfused hearts in the older age groups, accompanied with a slowed
      phase 4 spontaneous depolarization rate (90.5 +/- 4.7 vs 49.6 +/- 2.6 mV/s for 2
      week vs 4 week hearts, respectively; n = 5; P < 0.05), a negative shift of the If
      threshold potential (-45.5 +/- 3.0 vs -51.1 +/- 6.0 mV for 2 week vs 4 week
      hearts, respectively; n = 9; P < 0.05) and decreasing basal levels of SA nodal
      cAMP (0.31 +/- 0.05 vs 0.025 +/- 0.002 micromol/L for 2 week vs 4 week hearts,
      respectively; n = 6; P < 0.05). Gene expression levels of PDE1A, 4A and 8A were
      increased in the 12 week group compared with the 2 week group 1.5-, 2- and 1.8
      fold, respectively (P < 0.05), with little change in ADCY1 and 5. 4. These data
      suggest that, in addition to autonomic innervation, slowing of heart rate during
      postnatal maturation can be attributed to a negative shift of the If activation
      caused by diminished baseline cAMP content in SA nodal cells.

PMID- 16895553
TI  - The riddle of the dual expression of IgM and IgD.
AB  - Signalling through the B cell antigen receptor (BCR) is required for peripheral B
      lymphocyte maturation, maintenance, activation and silencing. In mature B cells,
      the antigen receptor normally consists of two isotypes, membrane IgM and IgD
      (mIgM, mIgD). Although the signals initiated from both isotypes differ in
      kinetics and intensity, in vivo, the BCR of either isotype seems to be able to
      compensate for the loss of the other, reflected by the mild phenotypes of mice
      deficient for mIgM or mIgD. Thus, it is still unclear why mature B cells need
      expression of mIgD in addition to mIgM. In the current review we suggest that the
      view that IgD has a simply definable function centred around the basic signalling
      function should be replaced by the assumption that IgD fine tunes humoral
      responses, modulates B cell selection and homeostasis and thus shapes the B cell
      repertoire, defining IgD to be a key modulator of the humoral immune response.

PMID- 16895554
TI  - Gene expression profiling of human macrophages at late time of infection with
      Mycobacterium tuberculosis.
AB  - Macrophages play an essential role in the immune response to Mycobacterium
      tuberculosis (Mtb). Previous transcriptome surveys, by means of micro- and
      macroarrays, investigated the cellular gene expression profile during the early
      phases of infection (within 48 hr). However, Mtb remains within the host
      macrophages for a longer period, continuing to influence the macrophage gene
      expression and, consequently, the environment in which it persists. Therefore, we
      studied the transcription patterns of human macrophages for up to 7 days after
      infection with Mtb. We used a macroarray approach to study 858 human genes
      involved in immunoregulation, and we confirmed by quantitative real-time reverse
      transcriptase polymerase chain reaction (q-rt RT-PCR) and by enzyme-linked
      immunosorbent assay the most relevant modulations. We constantly observed the up
      regulation in infected macrophages versus uninfected, of the following genes:
      interleukin-1 beta and interleukin-8, macrophage inflammatory protein-1 alpha,
      growth-related oncogene-beta, epithelial cell-derived neutrophil-activating
      peptide-78, macrophage-derived chemokine, and matrix metalloproteinase-7; whereas
      macrophage colony-stimulating factor-receptor and CD4 were down-regulated in
      infected macrophages. Mtb is able to withstand this intense cytokine
      microenvironment and to survive inside the human macrophage. Therefore we
      simultaneously investigated by q-rt RT-PCR the modulation of five mycobacterial
      genes: the alternative sigma factors sigA, sigE and sigG, the alpha-crystallin
      (acr) and the superoxide dismutase C (sodC) involved in survival mechanisms. The
      identified host and mycobacterial genes that were expressed until 7 days after
      infection, could have a role in the interplay between the host immune defences
      and the bacterial escape mechanisms.

PMID- 16895555
TI  - TAP1-/- mice present oligoclonal BV-BJ expansions following the rejection of
      grafts bearing self antigens.
AB  - Our previous work showed that transporter associated with antigen processing 1
      (TAP1)-/- (H-2b) mice rejected grafts from H-2b mice which display a normal
      density of class I major histocompatibility complex (MHC) molecules at the cell
      surface. Our results indicated that H-2b molecules themselves may be a target in
      this kind of rejection and that CD4+ T cells play a major role in this
      autoreactive process. Our data also suggested that TAP1-/- mice, in addition to
      the well-recognized phenotype of class I and CD8+ T-cell deficiency, present a
      functional alteration in their autoreactive CD4+ T-cell repertoires. In this
      model of inflammatory autoreactivity to modified self, we have analysed T-cell
      receptor (TCR) V-beta-J-beta (BV-BJ) usage by complementarity determining region
      3 (CDR3) length spectratyping in splenocytes from naive TAP1-/- mice and
      transplanted TAP1-/- mice that rejected B6 heart grafts or responded to synthetic
      self H-2Kb peptides. Importantly, oligoclonal T-cell expansions shared by
      different animals were detected in the peripheral T-cell repertoire of
      transplanted TAP1-/- mice. Such public expansions were also induced in vitro by H
      2Kb peptides, suggesting that dominant class I peptides can induce preferential
      expansions of restricted T-cell populations during rejection. Some of these
      public T-cell expansions were also detected in transplanted mice even before in
      vitro stimulation with peptides, indicating that post-transplantation expansion
      of these populations had occurred in vivo. The functional activity of these T
      cell populations awaits elucidation, as do the underlying mechanisms involved in
      the inflammatory autoreactive process, in TAP1-/- mice.

PMID- 16895556
TI  - Anti-idiotype antibody induced cellular immunity in mice transgenic for human
      carcinoembryonic antigen.
AB  - In the present study, we have analysed the detailed cellular immune mechanisms
      involved in tumour rejection in carcinoembryonic antigen (CEA) transgenic mice
      after immunization with dendritic cells (DC) pulsed with an anti-idiotype (Id)
      antibody, 3H1, which mimics CEA. 3H1-pulsed DC vaccinations resulted in induction
      of CEA specific cytotoxic T lymphocyte (CTL) responses in vitro and the rejection
      of CEA-transfected MC-38 murine colon carcinoma cells, C15, in vivo (Saha et
      al.,Cancer Res 2004; 64: 4995-5003). These CTL mediated major histocompatibility
      complex (MHC) class I-restricted tumour cell lysis, production of interferon
      gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha), and expression of
      Fas ligand (FasL) and TNF-related apoptosis-inducing ligand (TRAIL) in response
      to C15 cells. CTL used perforin-, FasL-, and TRAIL-mediated death pathways to
      lyse C15 cells, although perforin-mediated killing was the predominant lytic
      mechanism in vitro. The cytokines IFN-gamma and TNF-alpha synergistically
      enhanced surface expression of Fas, TRAIL receptor, MHC class I and class II on
      C15 cells that increased the sensitivity of tumour cells to CTL lysis. CTL
      activity generated in 3H1-pulsed DC immunized mice was directed against an
      epitope defined by the idio-peptide LCD-2, derived from 3H1. In vivo lymphocyte
      depletion experiments demonstrated that induction of CTL response and antitumour
      immunity was dependent on both CD4+ and CD8+ T cells. The analysis of splenocytes
      of immunized mice that had rejected C15 tumour growth revealed up-regulated
      surface expression of memory phenotype Ly-6C and CD44 on both CD4+ and CD8+ T
      cells. The adoptive transfer experiments also suggested the role of both CD4+ and
      CD8+ T cells in this model system. Furthermore, mice that had rejected C15 tumour
      growth, developed tumour-specific immunological memory.

PMID- 16895558
TI  - Control of the innate epithelial antimicrobial response is cell-type specific and
      dependent on relevant microenvironmental stimuli.
AB  - Immune defence against microbes depends in part on the production of
      antimicrobial peptides, a process that occurs in a variety of cell types but is
      incompletely understood. In this study, the mechanisms responsible for the
      induction of cathelicidin and beta-defensin antimicrobial peptides were found to
      be independent and specific to the cell type and stimulus. Vitamin D3 induced
      cathelicidin expression in keratinocytes and monocytes but not in colonic
      epithelial cells. Conversely, butyrate induced cathelicidin in colonic epithelia
      but not in keratinocytes or monocytes. Distinct factors induced beta-defensin
      expression. In all cell types, vitamin D3 activated the cathelicidin promoter and
      was dependent on a functional vitamin D responsive element. However, in colonic
      epithelia butyrate induced cathelicidin expression without increasing promoter
      activity and vitamin D3 activated the cathelicidin promoter without a subsequent
      increase in transcript accumulation. Induction of cathelicidin transcript
      correlated with increased processed mature peptide and enhanced antimicrobial
      activity against Staphylococcus aureus. However, induction of beta-defensin-2
      expression did not alter the innate antimicrobial capacity of cells in culture.
      These data suggest that antimicrobial peptide expression is regulated in a tissue
      specific manner at transcriptional, post-transcriptional and post-translational
      levels. Furthermore, these data show for the first time that innate antimicrobial
      activity can be triggered independently of the release of other pro-inflammatory
      molecules, and suggest strategies for augmenting innate immune defence without
      increasing inflammation.

PMID- 16895561
TI  - [Doctor protests in established areas].

PMID- 16895557
TI  - Interleukin-5 regulates genes involved in B-cell terminal maturation.
AB  - Interleukin (IL)-5 induces CD38-activated splenic B cells to differentiate into
      immunoglobulin M-secreting cells and undergo micro to gamma 1 class switch
      recombination (CSR) at the DNA level, resulting in immunoglobulin G1 (IgG1)
      production. Interestingly, IL-4, a well-known IgG1-inducing factor does not
      induce immunoglobulin production or micro to gamma 1 CSR in CD38-activated B
      cells. In the present study, we implemented complementary DNA microarrays to
      investigate the contribution of IL-5-induced gene expression in CD38-stimulated B
      cells to immunoglobulin-secreting cell differentiation and micro to gamma 1 CSR.
      IL-5 and IL-4 stimulation of CD38-activated B cells induced the expression of 418
      and 289 genes, respectively, that consisted of several clusters. Surprisingly, IL
      5-inducible 78 genes were redundantly regulated by IL-4. IL-5 and IL-4 also
      suppressed the gene expression of 319 and 325 genes, respectively, 97 of which
      were overlapped. Genes critically regulated by IL-5 include immunoglobulin
      related genes such as J chain and immunoglobulinkappa, and genes involved in B
      cell maturation such as BCL6, activation-induced cytidine deaminase (Aid) and B
      lymphocyte-induced maturation protein-1 (Blimp-1) and tend to be induced slowly
      after IL-5 stimulation. Intriguingly, among genes, the retroviral induction of
      Blimp-1 and Aid in CD38-activated B cells could induce IL-4-dependent maturation
      to Syndecan-1+ antibody-secreting cells and micro to gamma 1 CSR, respectively,
      in CD38-activated B cells. Taken together, preferential Aid and Blimp-1
      expression plays a critical role in IL-5-induced immunoglobulin-secreting cell
      differentiation and micro to gamma 1 CSR in CD38-activated B cells.

PMID- 16895559
TI  - The lack of RNA-dependent protein kinase enhances susceptibility of mice to
      genital herpes simplex virus type 2 infection.
AB  - Mice deficient in RNA-dependent protein kinase (PKR-/-) or deficient in PKR and a
      functional 2',5'-oligoadenylate synthetase (OAS) pathway (PKR/RL-/-) are more
      susceptible to genital herpes simplex virus type 2 (HSV-2) infection than wild
      type mice or mice that are deficient only in a functional OAS pathway (RL-/-) as
      measured by survival over 30 days. The increase in susceptibility correlated with
      an increase in virus titre recovered from vaginal tissue or brainstem of infected
      mice during acute infection. There was also an increase in CD45+ cells and CD8+ T
      cells residing in the central nervous system of HSV-2-infected PKR/RL-/- mice in
      comparison with RL-/- or wild-type control animals. In contrast, there was a
      reduction in the HSV-specific CD8+ T cells within the draining lymph node of the
      PKR/RL-/- mice. Collectively, activation of PKR, but not of OAS, contributes
      significantly to the local control and spread of HSV-2 following genital
      infection.

PMID- 16895562
TI  - [The status of staff female and male physicians in Germany in the year 2006].

PMID- 16895560
TI  - Costimulation of naive human CD4 T cells through intercellular adhesion molecule
      1 promotes differentiation to a memory phenotype that is not strictly the result
      of multiple rounds of cell division.
AB  - The process by which naive T cells become activated, differentiate into effector
      cells and ultimately generate long-lived memory cells is dependent upon a number
      of factors, including the costimulatory signals received by the T cell. To best
      understand the multiple events involved, it is important to understand the
      potential contributions by individual signalling proteins using both in vitro and
      in vivo studies. Here, the potential for costimulation through intercellular
      adhesion molecule-1 (ICAM-1; CD54), resident on the surface of naive human T
      cells, to influence differentiation was investigated. Costimulation of naive T
      cells through ICAM-1 resulted in expansive cell division, high interleukin-2
      production, and protection from apoptosis. Prolonged culture led to outgrowth of
      a subpopulation of cells with a highly differentiated CD45RA- CD11a(hi) CD27-
      phenotype. In this respect, costimulation through ICAM-1 was similar to
      costimulation through CD28 and different from costimulation through leucocyte
      function-associated antigen-1. The CD45RA- CD11a(hi) CD27- cells responded to
      suboptimal stimulation through the T-cell receptor alone with a more robust
      proliferative response compared with naive cells from the same subject. These
      cells also secreted higher levels of T helper type 1 cytokines in response to
      lower levels of stimulation than their naive counterparts. The surface phenotype
      and more sensitive response characteristics suggest the creation of a memory T
      cell subpopulation as a result of costimulation through ICAM-1. Finally,
      generation of this memory population was the result of specific costimulatory
      signals, and not merely because of a high number of cell divisions. These data
      reveal a new role for resident ICAM-1 to influence the differentiation of naive T
      cells.

PMID- 16895564
TI  - [Differential diagnoses in leg ulcers].
AB  - In Germany about 0.7% of the adult population have a chronic leg ulcer. Although
      chronic venous insufficiency accounts for at least 80% of all chronic leg ulcers,
      knowledge of the relevant differential diagnostic considerations is of crucial
      importance, in particular for patients who are refractory to therapy. In addition
      to vascular disease, other causes include neuropathic, metabolic, hematologic and
      exogenous factors as well as neoplasias, infections, drugs, genetic defects and
      some primary skin disorders. For the long-term successful treatment of patients
      with chronic leg ulcers, it is necessary to identify all relevant factors, in
      order to enable a pathogenesis-oriented, interdisciplinary therapeutic approach.

PMID- 16895565
TI  - [Immunotherapy of malignant melanoma--basic principles and novel therapeutic
      approaches].
AB  - Immunotherapy has assumed increasing importance in the therapy of malignant
      melanoma. The main reason is the high immunogenicity of the tumor itself, so that
      an immune response against the tumor often exists even without immune
      stimulation. The goal of modern immunotherapeutic approaches is to augment these
      anti-tumoral immune reactions to fight the tumor. Despite multiple successes, the
      ultimate breakthrough in the therapy of malignant melanoma has not yet been
      achieved. This overview summarizes the reasons for this lack of success and
      highlights future strategies for more successful therapy of malignant melanoma.

PMID- 16895566
TI  - [Trichophyton eboreum--a recently described dermatophyte].
AB  - BACKGROUND: The distribution of distinct species of dermatophytes is continuously
      changing and different species of dermatophytes can cause the same type of tinea.
      Therefore, it is necessary to always identify the pathogenic agents in
      dermatophytoses. PATIENTS AND METHODS: An unusual fungus was isolated from
      moccasin type tinea pedis in a HIV-positive immunocompromised patient from the
      Ivory Coast and characterized by morphological, physiological and genetic
      methods. RESULTS: The strain under study showed typical characteristics of
      dermatophytes but considering all its morphologic, physiologic and genetic
      features it unambiguously differed from all previously described species.
      CONCLUSION: The strain was recently described as a new dermatophyte species
      (Trichophyton eboreum). Distribution and pathogenicity of this species are as yet
      unknown.

PMID- 16895567
TI  - [Angioma serpiginosum following the lines of Blaschko--an effective treatment
      with the IPL technology].
AB  - Angioma serpiginosum, first described by Hutchinson in 1889, is a rare benign
      vascular nevus with dilatation and proliferation of the capillaries in the upper
      dermis. A 15-year-old boy presented with an angioma serpiginosum on the right
      side of the body following the lines of Blaschko. Both the clinical pattern and
      the appearance in a male are unusual. Treatment with IPL technology (intense
      pulsed light), which emits polychromatic light from a high-intensity flashlamp,
      proved to be an effective approach.

PMID- 16895568
TI  - [Acne infantum as presenting symptom of congenital adrenal hyperplasia due to 11
      beta-hydroxylase deficiency].
AB  - Infantile acne is a rare condition which usually begins after the third month of
      life and appears mainly on the cheeks. Spontaneous healing typically occurs
      within 2 years. A 2-year-old boy developed acne infantum during the first days
      after birth; it failed to respond to topical treatment. Detailed physical
      examination and endocrinologic evaluation confirmed the presumed diagnosis of
      congenital adrenal hyperplasia (CAH), and showed it was caused by 11-beta
      hydroxylase deficiency. CAH comprises a group of autosomal-recessively inherited
      disorders. These hereditary enzyme defects in steroid biosynthesis cause
      glucocorticoid deficiency and an overproduction of biosynthetic precursor
      steroids. Adrenal androgen biosynthesis is not impaired but shows a massive
      reactive overproduction due to the increased ACTH secretion within the up
      regulated hypothalamo-pituitary-adrenal system. The characteristic features of
      CAH in male infants are demonstrated on the basis of this case report.

PMID- 16895569
TI  - [Special features of topical and systemic dermatologic therapy in children].

PMID- 16895570
TI  - [Papules on the right lower leg of an African girl].

PMID- 16895572
TI  - [Melanocytic nevi].

PMID- 16895571
TI  - [Brief guidelines--dermatofibrosarcoma protuberans].

PMID- 16895575
TI  - [On the history of dermatology in Austria].

PMID- 16895576
TI  - [Antibody and antibody-targeted therapy].

PMID- 16895577
TI  - Inhibition of histone deacetylation protects wild-type but not gelsolin-deficient
      neurons from oxygen/glucose deprivation.
AB  - Histone acetylation and deacetylation participate in the epigenetic regulation of
      gene expression. In this paper, we demonstrate that pre-treatment with the
      histone deacetylation inhibitor trichostatin A (TSA) enhances histone acetylation
      in primary cortical neurons and protects against oxygen/glucose deprivation, a
      model for ischaemic cell death in vitro. The actin-binding protein gelsolin was
      identified as a mediator of neuroprotection by TSA. TSA enhanced histone
      acetylation of the gelsolin promoter region, and up-regulated gelsolin messenger
      RNA and protein expression in a dose- and time-dependent manner. Double-label
      confocal immunocytochemistry visualized the up-regulation of gelsolin and histone
      acetylation within the same neuron. Together with gelsolin up-regulation, TSA pre
      treatment decreased levels of filamentous actin. The neuroprotective effect of
      TSA was completely abolished in neurons lacking gelsolin gene expression. In
      conclusion, we demonstrate that the enhancement of gelsolin gene expression
      correlates with neuroprotection induced by the inhibition of histone
      deacetylation.

PMID- 16895578
TI  - Effects of the cholesterol-lowering compound methyl-beta-cyclodextrin in models
      of alpha-synucleinopathy.
AB  - The aggregation of alpha-synuclein (alpha-syn) is believed to play a critical
      role in the pathogenesis of disorders such as dementia with Lewy bodies and
      Parkinson's disease. The function of alpha-syn remains unclear, although several
      lines of evidence suggest that alpha-syn is involved in synaptic vesicle
      trafficking, probably via lipid binding, and interactions with lipids have been
      shown to regulate alpha-syn aggregation. In this context, the main objective of
      this study was to determine whether methyl-beta-cyclodextrin (MbetaCD), a
      cholesterol-extracting agent, interfered with alpha-syn accumulation in models of
      synucleinopathy. For this purpose, we studied the effects of MbetaCD on the
      accumulation of alpha-syn in a transfected neuronal cell line and in transgenic
      mice. Immunoblot analysis showed that MbetaCD reduced the level of alpha-syn in
      the membrane fraction and detergent-insoluble fraction of transfected cells. In
      agreement with the in vitro studies, treatment of mice with MbetaCD resulted in
      decreased levels of alpha-syn in membrane fractions and reduced accumulation of
      alpha-syn in the neuronal cell body and synapses. Taken together, these results
      suggest that changes in cholesterol and lipid composition using cholesterol
      lowering agents may be used as a tool for the treatment of synucleinopathies.

PMID- 16895579
TI  - Genotype-dependent priming to self- and xeno-cannibalism in heterozygous and
      homozygous lymphoblasts from patients with Huntington's disease.
AB  - In the present work, we studied the mitochondrial function and cell death
      pathway(s) in heterozygous and homozygous immortalized cell lines from patients
      with Huntington's disease (HD). Heterozygosis was characterized by specific
      alterations in mitochondrial membrane potential, a constitutive hyperpolarization
      state of mitochondria, and was correlated with an increased susceptibility to
      apoptosis. Lymphoblasts from homozygous patients, on the other hand, were
      characterized by a significant percentage of cells displaying autophagic
      vacuoles. These cells also demonstrated a striking attitude towards significant
      cannibalistic activity. Considering the pathogenic role of cell death in HD, our
      study provides new and useful insights into the role of mitochondrial
      dysfunction, i.e. hyperpolarization, in hijacking HD heterozygous cells towards
      apoptosis and HD homozygous cells towards a peculiar phenotype characterized by
      both self- and xeno-cannibalism. These events can, however, be viewed as an
      ultimate attempt to survive rather than a way to die. The present work underlines
      the possibility that HD-associated mitochondrial defects could tentatively be by
      passed by the cells by activating cellular 'phagic' activities, including so
      called 'mitophagy' and 'cannibalism', that only finally lead to cell death.

PMID- 16895580
TI  - Proteomic analysis of rat hippocampal plasma membrane: characterization of
      potential neuronal-specific plasma membrane proteins.
AB  - The hippocampus is a distinct brain structure that is crucial in memory storage
      and retrieval. To identify comprehensively proteins of hippocampal plasma
      membrane (PM) and detect the neuronal-specific PM proteins, we performed a
      proteomic analysis of rat hippocampus PM using the following three technical
      strategies. First, proteins of the PM were purified by differential and density
      gradient centrifugation from hippocampal tissue and separated by one-dimensional
      electophoresis, digested with trypsin and analyzed by electrospray ionization
      (ESI) quadrupole time-of-flight (Q-TOF) tandem mass spectrometry (MS/MS). Second,
      the tryptic peptide mixture from PMs purified from hippocampal tissue using the
      centrifugation method was analyzed by liquid chromatography ion-trap ESI-MS/MS.
      Finally, the PM proteins from primary hippocampal neurons purified by a biotin
      directed affinity technique were separated by one-dimensional electrophoresis,
      digested with trypsin and analyzed by ESI-Q-TOF-MS/MS. A total of 345, 452 and
      336 non-redundant proteins were identified by each technical procedure
      respectively. There was a total of 867 non-redundant protein entries, of which
      64.9% are integral membrane or membrane-associated proteins. One hundred and
      eighty-one proteins were detected only in the primary neurons and could be
      regarded as neuronal PM marker candidates. We also found some hypothetical
      proteins with no functional annotations that were first found in the hippocampal
      PM. This work will pave the way for further elucidation of the mechanisms of
      hippocampal function.

PMID- 16895581
TI  - Cell-permeable peptide antioxidants as a novel therapeutic approach in a mouse
      model of amyotrophic lateral sclerosis.
AB  - Reactive oxygen species (ROS) play a major role in the pathogenesis of
      neurodegenerative diseases. They are important contributors to necrotic and
      apoptotic cell death. A major proportion of cellular ROS is generated at the
      inner mitochondrial membrane by the respiratory chain. In the present study, we
      investigated a novel peptide antioxidant (SS-31) targeted to the inner
      mitochondrial membrane for its therapeutic effects both in vitro and in vivo in
      the G93A mouse model of amyotrophic lateral sclerosis (ALS). SS-31 protected
      against cell death induced by hydrogen peroxide in vitro in neuronal cells stably
      transfected with either wild-type or mutant Cu/Zn superoxide dismutase (SOD1).
      Daily intraperitoneal injections of SS-31 (5 mg/kg), starting at 30 days of age,
      led to a significant improvement in survival and motor performance. In comparison
      with vehicle-treated G93A mice, SS-31-treated mice showed a decreased cell loss
      and a decrease in immunostaining for markers of oxidative stress in the lumbar
      spinal cord. This further enhances the concept that pharmacological modification
      of oxidative stress is a therapeutic option for the treatment of ALS.

PMID- 16895582
TI  - Glial cell-line derived neurotrophic factor and neurturin regulate the
      expressions of distinct miRNA precursors through the activation of GFRalpha2.
AB  - Glial cell line-derived neurotrophic factor (GDNF) and neurturin (NTN) are
      structurally related neurotrophic factors that have both been shown to prevent
      the degeneration of dopaminergic neurons in vitro and in vivo. NTN and GDNF are
      thought to bind with different affinities to the GDNF family receptor alpha-2
      (GFRalpha2), and can activate the same multi-component receptor system consisting
      of GFRalpha2, receptor tyrosine kinase Ret (RET) and NCAM. MicroRNAs (miRNAs) are
      a class of short, non-coding RNAs that regulate gene expression through
      translational repression or RNA degradation. miRNAs have diverse functions,
      including regulating differentiation, proliferation and apoptosis in several
      organisms. It is currently unknown whether GDNF and NTN regulate the expression
      of miRNAs through activation of the same multi-component receptor system. Using
      quantitative real-time PCR, we measured the expression of some miRNA precursors
      in human BE(2)-C cells that express GFRalpha2 but not GFRalpha1. GDNF and NTN
      differentially regulate the expression of distinct miRNA precursors through the
      activation of mitogen-activated protein kinase (extracellular signal-regulated
      kinase 1/2). This study showed that the expression of distinct miRNA precursors
      is differentially regulated by specific ligands through the activation of
      GFRalpha2.

PMID- 16895583
TI  - Region-specific regulation of glucocorticoid receptor/HSP90 expression and
      interaction in brain.
AB  - The hippocampal glucocorticoid receptor (GR) is involved in negative feedback
      regulation of the hypothalamo-pituitary-adrenal axis and is believed to transduce
      the deleterious effects of glucocorticoids in depression and age-related memory
      loss. Regulation and intracellular trafficking of the GR are critical
      determinants of GR action in both health and disease. Here, we show dynamic
      regulation of GR and its interaction with its principal intracellular chaperone,
      heat-shock protein (HSP) 90, across the circadian cycle. Our initial experiments
      indicate that cytosolic hippocampal GR protein is elevated in the evening (PM),
      whereas nuclear GR and cytosolic HSP90, HSP70 and heat-shock cognate 70 (HSC70),
      are unchanged. In contrast, there are no changes in examined proteins in the
      hypothalamus. Immunoprecipitation experiments reveal increased GR-HSP90
      associations in the hippocampus in the PM, whereas binding in the hypothalamus is
      decreased in the PM. Given that GR requires HSP90 for ligand binding, the data
      suggest that circadian GR signaling capacity is regulated in a region-specific
      pattern.

PMID- 16895584
TI  - Calpain inhibitors and antioxidants act synergistically to prevent cell necrosis:
      effects of the novel dual inhibitors (cysteine protease inhibitor and
      antioxidant) BN 82204 and its pro-drug BN 82270.
AB  - Cell death is a common feature observed in neurodegenerative disorders, and is
      often associated with calpain activation and overproduction of reactive oxygen
      species (ROS). This study investigated the use of calpain inhibitors and
      antioxidants in combination to protect cells against necrosis. Maitotoxin (MTX),
      which induces a massive influx of calcium, was used to provoke neuronal cell
      death. This toxin increased, in a concentration-dependent manner, both calpain
      activity and ROS formation. Calpain inhibitors or antioxidants inhibited MTX
      induced necrosis only marginally (below 20%), whereas their association protected
      against cell death by 40-66% in a synergistic manner. BN 82204, which possesses
      both calpain-cathepsin L inhibitory and antioxidant properties, and its
      acetylated pro-drug BN 82270, totally protected cells at 100 microm. The pro-drug
      BN 82270, which had better cell penetration, was twice as effective as the active
      principle BN 82204 in protecting glioma C6 or neuroblastoma SHSY5Y cells against
      death. These results suggest the potential therapeutic relevance of using a
      single molecule with multiple activities (cysteine protease
      inhibitor/antioxidant), and warrant further in vivo investigations in models of
      neuronal disorders.

PMID- 16895585
TI  - Altered signaling pathways underlying abnormal hippocampal synaptic plasticity in
      the Ts65Dn mouse model of Down syndrome.
AB  - The Ts65Dn mouse model of Down syndrome (DS) has an extra segment of chromosome
      (Chr.) 16 exhibits abnormal behavior, synaptic plasticity and altered function of
      several signaling molecules. We have further investigated signaling pathways that
      may be responsible for the impaired hippocampal plasticity in the Ts65Dn mouse.
      Here we report that calcium/calmodulin-dependent protein kinase II (CaMKII),
      phosphatidylinositol 3-kinase (PI3K)/Akt, extracellular signal-regulated kinase
      (ERK), protein kinase A (PKA) and protein kinase C (PKC), all of which have been
      shown to be involved in synaptic plasticity, are altered in the Ts65Dn
      hippocampus. We found that the phosphorylation of CaMKII and protein kinase Akt
      was increased, whereas ERK was decreased. Activities of PKA and PKC were
      decreased. Furthermore, abnormal PKC activity and an absence of the increase in
      Akt phosphorylation were demonstrated in the Ts65Dn hippocampus after high
      frequency stimulation that induces long-term potentiation. Our findings suggest
      that abnormal synaptic plasticity in the Ts65Dn hippocampus is the result of
      compensatory alterations involving the glutamate receptor subunit GluR1 in either
      one or more of these signaling cascades caused by the expression of genes located
      on the extra segment of Chr. 16.

PMID- 16895586
TI  - Unconventional neuroprotection against Ca2+ -dependent insults by
      metalloporphyrin catalytic antioxidants.
AB  - We evaluated whether both inert and catalytically active metalloporphyrin
      antioxidants, meso-substituted with either phenyl-based or N-alkylpyridinium
      based groups, suppress Ca(2+)-dependent neurotoxicity in cell culture models of
      relevance to cerebral ischemia. Representatives from both metalloporphyrin
      classes, regardless of antioxidant strength, protected cultured cortical neurons
      or PC-12 cultures against the Ca(2+) ionophores ionomycin or A23187, by
      suppressing neurotoxic Ca(2+) influx. Some metalloporphyrins suppressed
      excitotoxic Ca(2+) influx indirectly induced by the Ca(2+) ionophores in cortical
      neurons. Metalloporphyrins did not quench intracellular fluorescence, suggesting
      localization to the plasma membrane interface and/or interference with Ca(2+)
      ionophores. Metalloporphyrins suppressed ionomycin-induced Mn(2+) influx, but did
      not protect cortical neurons against pyrithione, a Zn(2+) ionophore. In other
      Ca(2+)-dependent paradigms, Ca(2+) influx via plasma membrane depolarization, but
      not through reversal of plasmalemmal Na(+)/Ca(2+) exchangers, was modestly
      suppressed by Mn(III)meso-tetrakis(4-benzoic acid)porphyrin (Mn(III)TBAP) or by
      an inert analog, Zn(II)TBAP. Mn(III)TBAP and Zn(II)TBAP potently protected
      cortical neurons against long-duration oxygen-glucose deprivation (OGD),
      performed in the presence of antagonists of NMDA, alpha-amino-3-hydroxy-5
      methylisoxazole-4-propionate and L-type voltage-gated Ca(2+) channels, raising
      the possibility of an unconventional mode of blockade of transient receptor
      protein melastatin 7 channels by a metalloTBAP family of metalloporphyrins. The
      present study extends the range of Ca(2+)-dependent insults for which
      metalloporphyrins demonstrate unconventional neuroprotection. MetalloTBAPs appear
      capable of targeting an OGD temporal continuum.

PMID- 16895589
TI  - Significance and interpretation of elevated troponin in septic patients.
AB  - Because no bedside method is currently available to evaluate myocardial
      contractility independent of loading conditions, a biological marker that could
      detect myocardial dysfunction in the early stage of severe sepsis would be a
      helpful tool in the management of septic patients. Clinical and experimental
      studies have reported that plasma cardiac troponin levels are increased in sepsis
      and could indicate myocardial dysfunction and poor outcome. The high prevalence
      of elevated levels of cardiac troponins in sepsis raises the question of what
      mechanism results in their release into the circulation. Apart from focal
      ischemia, several factors may contribute to the microinjury and minimal
      myocardial cell damage in the setting of septic shock. A possible direct cardiac
      myocytotoxic effect of endotoxins, cytokines or reactive oxygen radicals induced
      by the infectious process and produced by activated neutrophils, macrophages and
      endothelial cells has been postulated. The presence of microvascular failure and
      regional wall motion abnormalities, which are frequently observed in positive
      troponin patients, also suggest ventricular wall strain and cardiac cell
      necrosis. Altogether, the available studies support the contention that cardiac
      troponin release is a valuable marker of myocardial injury in patients with
      septic shock.

PMID- 16895590
TI  - High-throughput genomic technology in research and clinical management of breast
      cancer. Molecular signatures of progression from benign epithelium to metastatic
      breast cancer.
AB  - It is generally accepted that early detection of breast cancer has great impact
      on patient survival, emphasizing the importance of early diagnosis. In a widely
      recognized model of breast cancer development, tumor cells progress through
      chronological and well defined stages. However, the molecular basis of disease
      progression in breast cancer remains poorly understood. High-throughput molecular
      profiling techniques are excellent tools for the study of complex molecular
      alterations. By accurately mapping changes in the genome and subsequent
      biological/molecular pathways, the chances of finding potential novel treatment
      targets as well as intervention strategies are enhanced, and ultimately lives can
      be saved. This review provides a brief summary of recent progress in identifying
      molecular markers for invasiveness in early breast lesions.

PMID- 16895592
TI  - Gingival and plaque decontamination: can we take a bite out of VAP?

PMID- 16895593
TI  - Limitations of caspofungin in the treatment of obstructive pyonephrosis due to
      Candida glabrata infection.
AB  - BACKGROUND: Caspofungin is a new antifungal agent with high-level activity
      against a number of Candida species including those that are resistant to azoles.
      Its good safety profile and low nephrotoxicity makes it an attractive drug to
      treat fungal infections in patients with compromised renal function. However,
      little is known about the clinical efficacy in the treatment of complicated
      urinary tract infections due to Candida species such as pyonephrosis. CASE
      PRESENTATION: We report a case of obstructive pyonephrosis due to an azole
      (fluconazole and itraconazole) resistant Candida glabrata strain that failed to
      respond to intravenous treatment with caspofungin. A sustained clinical and
      microbiological response was only achieved after percutaneous drainage and
      instillation of amphotericin B deoxycholate into the renal pelvis in combination
      with intravenous liposomal amphotericin B. CONCLUSION: This case demonstrates the
      limitation of intravenous antifungal agents such as caspofungin as the sole
      treatment of an obstructive upper urinary tract infection due to Candida species.
      In order to achieve long term sustained cure from an obstructive pyonephrosis,
      pus and fungal balls should be drained and an anti-fungal agent such as
      amphotericin B deoxycholate instilled locally. The pharmacokinetics and role of
      caspofungin in the treatment of complicated Candida urinary tract infection is
      reviewed.

PMID- 16895594
TI  - New insight into CCN3 interactions--nuclear CCN3 : fact or fantasy?
AB  - The identification of potential partners for CCN3(NOV) sheds new light on the
      biological activity of this signaling protein. In particular, the physical
      interaction of CCN3 with the IL33 cytokine combined with previous data indicating
      that CCN3 expression was regulated by TNFalpha and IL1 cytokines, point to CCN3
      as a potent player in a variety of inflammatory responses, including
      neurodegenerative disease, and arthritis. Nuclear proteins that are involved in
      the regulation of RNA processing and chromatin remodeling were also found to
      interact with CCN3. These observations reinforce the concept that routing of CCN3
      to the cell nucleus where it acts as a transcription regulator, might constitute
      a key element in the balance between the anti- and pro-proliferative activities
      of CCN3 proteins.

PMID- 16895595
TI  - Aggressive treatment of metastatic squamous cell carcinoma of the rectum to the
      liver: a case report and a brief review of the literature.
AB  - BACKGROUND: Rectal squamous cell carcinoma (SCC) is a rare tumor. The incidence
      of this malignancy has been reported to be 0.25 to 1 per 1000 colorectal
      carcinomas. From a review of the English literature 55 cases of SCC of the rectum
      have been published. In this study we report a rectal metastatic SCC to the
      liver, discussing the efficacy of aggressive adjuvant and neo-adjuvant therapies
      on survival and prognosis. CASE PRESENTATION: A 39-year-old female patient with a
      pure SCC of the rectum diagnosed endoscopically is presented. The patient
      underwent initially neoadjuvant chemo-radiotherapy and then abdominoperineal
      resection with concomitant bilateral oophorectomy and hysterectomy, followed by
      adjuvant chemo-radiotherapy. Five months after the initial operation liver
      metastasis was demonstrated and a liver resection was carried out, followed by
      adjuvant chemotherapy. Eighteen months after the initial operation the patient is
      alive. CONCLUSION: Although prognosis of rectal SCC is worse than that of
      adenocarcinoma, an aggressive therapeutic approach with surgery as the primary
      treatment, followed by combined neo- and adjuvant chemo-radiotherapy, may be
      necessary in order to improve survival and prognosis.

PMID- 16895596
TI  - Effects of prolonged endotoxemia on liver, skeletal muscle and kidney
      mitochondrial function.
AB  - INTRODUCTION: Sepsis may impair mitochondrial utilization of oxygen. Since
      hepatic dysfunction is a hallmark of sepsis, we hypothesized that the liver is
      more susceptible to mitochondrial dysfunction than the peripheral tissues, such
      as the skeletal muscle. We studied the effect of prolonged endotoxin infusion on
      liver, muscle and kidney mitochondrial respiration and on hepatosplanchnic oxygen
      transport and microcirculation in pigs. METHODS: 20 anesthetized pigs were
      randomized to receive endotoxin or saline infusion for 24 hours. Muscle, liver
      and kidney mitochondrial respiration was assessed. Cardiac output
      (thermodilution), carotid, superior mesenteric and kidney arterial, portal venous
      (ultrasound Doppler) and microcirculatory blood flow (laser Doppler) were
      measured, and systemic and regional oxygen transport and lactate exchange were
      calculated. RESULTS: Endotoxin infusion induced hyperdynamic shock and impaired
      the glutamate- and succinate-dependent mitochondrial respiratory control ratio
      (RCR) in the liver (glutamate: endotoxemia: median [range] 2.8 [2.3-3.8] vs.
      controls: 5.3 [3.8-7.0]; p<0.001; succinate: endotoxemia: 2.9 [1.9-4.3] vs.
      controls: 3.9 [2.6-6.3] p=0.003). While the ADP:O ratio was reduced with both
      substrates, maximal ATP production was impaired only in the succinate-dependent
      respiration. Hepatic oxygen consumption and extraction, and liver surface laser
      Doppler blood flow remained unchanged. Glutamate-dependent respiration in the
      muscle and kidney was unaffected. CONCLUSIONS: Endotoxemia reduces the efficiency
      of hepatic but neither skeletal muscle nor kidney mitochondrial respiration,
      independent of regional and microcirculatory blood flow changes.

PMID- 16895598
TI  - Distinct differentiation characteristics of individual human embryonic stem cell
      lines.
AB  - BACKGROUND: Individual differences between human embryonic stem cell (hESC) lines
      are poorly understood. Here, we describe the derivation of five hESC lines
      (called FES 21, 22, 29, 30 and 61) from frozen-thawed human embryos and compare
      their individual differentiation characteristic. RESULTS: The cell lines were
      cultured either on human or mouse feeder cells. The cells grew significantly
      faster and could be passaged enzymatically only on mouse feeders. However, this
      was found to lead to chromosomal instability after prolonged culture. All hESC
      lines expressed the established markers of pluripotent cells as well as several
      primordial germ cell (PGC) marker genes in a uniform manner. However, the cell
      lines showed distinct features in their spontaneous differentiation patterns. The
      embryoid body (EB) formation frequency of FES 30 cell line was significantly
      lower than that of other lines and cells within the EBs differentiated less
      readily. Likewise, teratomas derived from FES 30 cells were constantly cystic and
      showed only minor solid tissue formation with a monotonous differentiation
      pattern as compared with the other lines. CONCLUSION: hESC lines may differ
      substantially in their differentiation properties although they appear similar in
      the undifferentiated state.

PMID- 16895597
TI  - Integration of hybridization-based markers (overgos) into physical maps for
      comparative and evolutionary explorations in the genus Oryza and in Sorghum.
AB  - BACKGROUND: With the completion of the genome sequence for rice (Oryza sativa
      L.), the focus of rice genomics research has shifted to the comparison of the
      rice genome with genomes of other species for gene cloning, breeding, and
      evolutionary studies. The genus Oryza includes 23 species that shared a common
      ancestor 8-10 million years ago making this an ideal model for investigations
      into the processes underlying domestication, as many of the Oryza species are
      still undergoing domestication. This study integrates high-throughput,
      hybridization-based markers with BAC end sequence and fingerprint data to
      construct physical maps of rice chromosome 1 orthologues in two wild Oryza
      species. Similar studies were undertaken in Sorghum bicolor, a species which
      diverged from cultivated rice 40-50 million years ago. RESULTS: Overgo markers,
      in conjunction with fingerprint and BAC end sequence data, were used to build
      sequence-ready BAC contigs for two wild Oryza species. The markers drove contig
      merges to construct physical maps syntenic to rice chromosome 1 in the wild
      species and provided evidence for at least one rearrangement on chromosome 1 of
      the O. sativa versus Oryza officinalis comparative map. When rice overgos were
      aligned to available S. bicolor sequence, 29% of the overgos aligned with three
      or fewer mismatches; of these, 41% gave positive hybridization signals. Overgo
      hybridization patterns supported colinearity of loci in regions of sorghum
      chromosome 3 and rice chromosome 1 and suggested that a possible genomic
      inversion occurred in this syntenic region in one of the two genomes after the
      divergence of S. bicolor and O. sativa. CONCLUSION: The results of this study
      emphasize the importance of identifying conserved sequences in the reference
      sequence when designing overgo probes in order for those probes to hybridize
      successfully in distantly related species. As interspecific markers, overgos can
      be used successfully to construct physical maps in species which diverged less
      than 8 million years ago, and can be used in a more limited fashion to examine
      colinearity among species which diverged as much as 40 million years ago.
      Additionally, overgos are able to provide evidence of genomic rearrangements in
      comparative physical mapping studies.

PMID- 16895599
TI  - Stochastic modeling of empirical time series of childhood infectious diseases
      data before and after mass vaccination.
AB  - The goal of this paper is to analyze the stochastic dynamics of childhood
      infectious disease time series. We present an univariate time series analysis of
      pertussis, mumps, measles and rubella based on Box-Jenkins or AutoRegressive
      Integrated Moving Average (ARIMA) modeling. The method, which enables the
      dependency structure embedded in time series data to be modeled, has potential
      research applications in studies of infectious disease dynamics. Canadian
      chronological series of pertussis, mumps, measles and rubella, before and after
      mass vaccination, are analyzed to characterize the statistical structure of these
      diseases. Despite the fact that these infectious diseases are biologically
      different, it is found that they are all represented by simple models with the
      same basic statistical structure. Aside from seasonal effects, the number of new
      cases is given by the incidence in the previous period and by periodically
      recurrent random factors. It is also shown that mass vaccination does not change
      this stochastic dependency. We conclude that the Box-Jenkins methodology does
      identify the collective pattern of the dynamics, but not the specifics of the
      diseases at the biological individual level.

PMID- 16895600
TI  - The approximability of the String Barcoding problem.
AB  - The String Barcoding (SBC) problem, introduced by Rash and Gusfield (RECOMB,
      2002), consists in finding a minimum set of substrings that can be used to
      distinguish between all members of a set of given strings. In a computational
      biology context, the given strings represent a set of known viruses, while the
      substrings can be used as probes for an hybridization experiment via microarray.
      Eventually, one aims at the classification of new strings (unknown viruses)
      through the result of the hybridization experiment. In this paper we show that
      SBC is as hard to approximate as Set Cover. Furthermore, we show that the
      constrained version of SBC (with probes of bounded length) is also hard to
      approximate. These negative results are tight.

PMID- 16895601
TI  - The nosological significance of Folie a Deux: a review of the literature.
AB  - BACKGROUND: Folie a Deux is a rare syndrome that has attracted much clinical
      attention. There is increasing doubt over the essence of the condition and the
      validity of the original description, such that it remains an elusive entity
      difficult to define. METHOD: We conducted a systematic review of the literature
      of all cases reporting the phenomenon of Folie a Deux, from the years 1993-2005.
      RESULTS: 64 cases were identified of which 42 met the inclusion criteria. The
      diagnoses in the primary and secondary were more heterogeneous than current
      diagnostic criteria suggest. There exists a high degree of similarity between the
      primary and secondary in terms of susceptibility to psychiatric illness, family
      and past psychiatric history, than previously thought. CONCLUSION: Folie a Deux
      can occur in many situations outside the confines of the current classification
      systems and is not as rare as believed, and should alert the clinician to
      unrecognized psychiatric problems in the secondary.

PMID- 16895602
TI  - The yeast ubiquitin ligase SCFMet30: connecting environmental and intracellular
      conditions to cell division.
AB  - Ubiquitination regulates a host of cellular processes and is well known for its
      role in progression through the cell division cycle. In budding yeast, cadmium
      and arsenic stress, the availability of sulfur containing amino acids, and the
      intracellular concentration of S-adenosylmethionine are linked to cell cycle
      regulation through the ubiquitin ligase SCFMet30. Regulation is achieved by
      ubiquitination of the transcription factor Met4. Met4 activity is controlled by a
      regulatory K48-linked ubiquitin chain that is synthesized by Cdc34/SCFMet30. A
      ubiquitin-interacting-motif (UIM) present in Met4 prevents degradation of
      ubiquitinated Met4 allowing the ubiquitin chain to function as a reversible
      switch of Met4 activity. Here we discuss mechanisms of Met4 and SCFMet30
      regulation in response to intracellular and environmental conditions, and
      describe the integration of these signals with cell cycle control.

PMID- 16895603
TI  - Bloodstream infection following 217 consecutive systemic-enteric drained pancreas
      transplants.
AB  - BACKGROUND: Combined kidney pancreas transplantation (PTx) evolved as excellent
      treatment for diabetic nephropathy. Infections remain common and serious
      complications. METHODS: 217 consecutive enteric drained PTxs performed from 1997
      to 2004 were retrospectively analyzed with regard to bloodstream infection.
      Immunosuppression consisted of antithymocyteglobuline induction, tacrolimus,
      mycophenolic acid and steroids for the majority of cases. Standard perioperative
      antimicrobial prophylaxis consisted of pipercillin/tazobactam in combination with
      ciprofloxacin and fluconazole. RESULTS: One year patient, pancreas and kidney
      graft survival were 96.4%, 88.5% and 94.8%, surgical complication rate was 35%,
      rejection rate 30% and rate of infection 59%. In total 46 sepsis episodes were
      diagnosed in 35 patients (16%) with a median onset on day 12 (range 1-45) post
      transplant. Sepsis source was intraabdominal infection (IAI) (n = 21), a
      contaminated central venous line (n = 10), wound infection (n = 5), urinary tract
      infection (n = 2) and graft transmitted (n = 2). Nine patients (4%) experienced
      multiple episodes of sepsis. Overall 65 pathogens (IAI sepsis 39, line sepsis 15,
      others 11) were isolated from blood. Gram positive cocci accounted for 50
      isolates (77%): Coagulase negative staphylococci (n = 28, i.e. 43%) (nine multi
      resistant), Staphylococcus aureus (n = 11, i.e. 17%) (four multi-resistant),
      enterococci (n = 9, i.e. 14%) (one E. faecium). Gram negative rods were cultured
      in twelve cases (18%). Patients with blood borne infection had a two year
      pancreas graft survival of 76.5% versus 89.4% for those without sepsis (p =
      0.036), patient survival was not affected. CONCLUSION: Sepsis remains a serious
      complication after PTx with significantly reduced pancreas graft, but not patient
      survival. The most common source is IAI.

PMID- 16895604
TI  - A novel approach to simultaneously scan genes at fragile sites.
AB  - BACKGROUND: Fragile sites are regions of the genome sensitive to replication
      stress and to exposure to environmental carcinogens. The two most commonly
      expressed fragile sites FRA3B and FRA16D host the histidine triad (FHIT) and WW
      domain containing oxidoreductase (WWOX) genes respectively. There is growing
      evidence that both genes contribute to cancer development and they are frequently
      altered by allelic and homozygous deletions in a variety of tumors. Their status
      is linked to prognosis in several malignancies and they are thought to be
      involved in early tumorigenesis. The loci for FHIT and WWOX both span over a
      megabase but the genes encode for small transcripts. Thus the screening of
      intragenic deletion can be difficult and has relied on loss of heterozygosity LOH
      assays, or genomic arrays. METHODS: Multiplex ligation dependent probe
      amplification MLPA, allows for the detection of deletions/duplications and
      relative quantification of up to 40 specific probes in a single assay. A
      FHIT/WWOX MLPA assay was designed, applied and validated in five esophageal
      squamous cell carcinoma ESCC, cell lines established in South Africa where this
      cancer is of high prevalence. Sixteen probes covered all FHIT exons and 7 probes
      covered WWOX. RESULTS: Both homozygous and hemizygous deletions were detected in
      FHIT, in four of the cell lines with a preferential deletion of exons 5 and 4.
      Chromosome 3 short arm was present in normal copy number indicating that
      deletions were site specific. In contrast WWOX was not altered in any cell lines.
      RT-PCR expression pattern paralleled the pattern of deletions. Ten primary ESCC
      tumor specimens were subsequently screened with this assay. FHIT exon deletions
      were found in four of them. CONCLUSION: This method offers an alternative to loss
      of heterozygosity studies. Simultaneous scanning of FHIT and WWOX exons in the
      context of early tumorigenesis and tumor progression, may help clarify the
      mechanistic events related to cancer development which are not revealed by immuno
      histochemistry assays. The presence of site specific deletions of FHIT in these
      cell lines and primary tumors support its possible role in South African ESCC and
      justifies a wider screening.

PMID- 16895605
TI  - Salvage for cervical recurrences of head and neck cancer with dissection and
      interstitial high dose rate brachytherapy.
AB  - Salvage therapy in head and neck cancer (HNC) is a controversy issue and the
      literature is scarce regarding the use of interstitial high-dose rate
      brachytherapy (I-HDR) in HNC. We evaluated the long-term results of a treatment
      policy combining salvage surgery and I-HDR for cervical recurrences of HNC.
      Charts of 21 patients treated from 1994 to 2004 were reviewed. The crude local
      control rate for all patients was 52.4%. The 5- and 8-years overall (OS) and
      local relapse-free survival (LRFS) rates were 50%, 42.9%, 42.5% and 28.6%,
      respectively. The only predictive factor associated to LFRS and OS was negative
      margin status (p = 0.0007 and p = 0.0002). We conclude that complete surgery is
      mandatory for long term control and the doses given by brachytherapy are not high
      enough to compensate for microscopic residual disease after surgery.

PMID- 16895607
TI  - Effect of heat and moisture exchanger (HME) positioning on inspiratory gas
      humidification.
AB  - BACKGROUND: In mechanically ventilated patients, we investigated how positioning
      the heat and moisture exchanger (HME) at different places on the ventilator
      circuit affected inspiratory gas humidification. METHODS: Absolute humidity (AH)
      and temperature (TEMP) at the proximal end of endotracheal tube (ETT) were
      measured in ten mechanically ventilated patients. The HME was connected either
      directly proximal to the ETT (Site 1) or at before the circuit Y-piece (Site 2:
      distance from proximal end of ETT and Site 2 was about 19 cm) (Figure. 1). Two
      devices, Hygrobac S (Mallinckrodt Dar, Mirandola, Italy) and Thermovent HEPA
      (Smiths Medical International Ltd., Kent, UK) were tested. AH and TEMP were
      measured with a hygrometer (Moiscope, MERA Co., Ltd., Tokyo, Japan). RESULTS:
      Hygrobac S provided significantly higher AH and TEMP at both sites than
      Thermovent HEPA. Both Hygrobac S and with Thermovent HEPA provided significantly
      higher AH and TEMP when placed proximally to the ETT. CONCLUSION: Although
      placement proximal to the ETT improved both AH and TEMP in both HMEs tested, one
      HME performed better in the distal position than the other HME in the proximal
      position. We conclude the both the type and placement of HME can make a
      significant difference in maintaining AH and TEMP during adult ventilation.

PMID- 16895606
TI  - Phenomenology and management of cognitive and behavioral disorders in Parkinson's
      disease. Rise and logic of dementia in Parkinson's disease.
AB  - An overview of studies on the issue of dementia in Parkinson's disease shows
      that, over time, there has been an evolution in the perception of the magnitude
      of the problem and of its nature. Dementia seems today to be part of the disease.
      This change in the understanding of the disease can be accounted for by various
      methodological problems and by difficulties, on one hand, in the definition of
      dementia and its differentiation from other conditions, and, on the other hand,
      in the diagnosis of the disease itself in individual cases. Optimal therapeutic
      strategies are also examined, either based on cholinesterase inhibitors or
      antiparkinsonian drugs and symptomatic measures.

PMID- 16895608
TI  - Tools for knowledge acquisition within the NeuroScholar system and their
      application to anatomical tract-tracing data.
AB  - BACKGROUND: Knowledge bases that summarize the published literature provide
      useful online references for specific areas of systems-level biology that are not
      otherwise supported by large-scale databases. In the field of neuroanatomy,
      groups of small focused teams have constructed medium size knowledge bases to
      summarize the literature describing tract-tracing experiments in several species.
      Despite years of collation and curation, these databases only provide partial
      coverage of the available published literature. Given that the scientists reading
      these papers must all generate the interpretations that would normally be entered
      into such a system, we attempt here to provide general-purpose annotation tools
      to make it easy for members of the community to contribute to the task of data
      collation. RESULTS: In this paper, we describe an open-source, freely available
      knowledge management system called 'NeuroScholar' that allows straightforward
      structured markup of the PDF files according to a well-designed schema to capture
      the essential details of this class of experiment. Although, the example worked
      through in this paper is quite specific to neuroanatomical connectivity, the
      design is freely extensible and could conceivably be used to construct local
      knowledge bases for other experiment types. Knowledge representations of the
      experiment are also directly linked to the contributing textual fragments from
      the original research article. Through the use of this system, not only could
      members of the community contribute to the collation task, but input data can be
      gathered for automated approaches to permit knowledge acquisition through the use
      of Natural Language Processing (NLP). CONCLUSION: We present a functional,
      working tool to permit users to populate knowledge bases for neuroanatomical
      connectivity data from the literature through the use of structured
      questionnaires. This system is open-source, fully functional and available for
      download from [1].

PMID- 16895609
TI  - Can volunteer companions prevent falls among inpatients? A feasibility study
      using a pre-post comparative design.
AB  - BACKGROUND: Falls in hospital are frequent and their consequences place an
      increased burden on health services. We evaluated a falls prevention strategy
      consisting of the introduction of volunteers to 'sit' with patients identified as
      being at high risk of falling. METHODS: Two four bed 'safety bays' located on
      medical wards in two hospitals within southern Adelaide were used. Ward fall
      rates (expressed as falls per 1000 occupied bed days) were compared in the
      baseline period (February-May 2002) with the implementation period (February -
      May 2003) using incident rate ratios and 95% confidence intervals. The number of
      hours of volunteered time was also collected. RESULTS: No patient falls occurred
      on either site when volunteers were present. However, there was no significant
      impact on overall ward fall rates. In the baseline period, there were 70 falls in
      4828 OBDs (14.5 falls per 1000 OBDs). During the implementation period, there
      were 82 falls in 5300 OBDs (15.5 falls per 1000 OBD). The IRR for falls in the
      implementation versus baseline period was 1.07 (95%CI 0.77 - 1.49; P = 0.346).
      Volunteers carried out care activities (e.g. cutting up food), provided company,
      and on occasions advocated on behalf of the patients. Volunteers donated 2345
      hours, at an estimated value to the hospitals of almost $57,000. CONCLUSION:
      Volunteers may play an important and cost-effective role in enhancing health care
      and can prevent falls in older hospital patients when they are present. Full
      implementation of this program would require the recruitment of adequate numbers
      of volunteers willing to sit with all patients considered at risk of falling in
      hospital. The challenge for future work in this area remains the sustainability
      of falls prevention strategies.

PMID- 16895610
TI  - Bactericidal activity of M protein conserved region antibodies against group A
      streptococcal isolates from the Northern Thai population.
AB  - BACKGROUND: Most group A streptococcal (GAS) vaccine strategies have focused on
      the surface M protein, a major virulence factor of GAS. The amino-terminus of the
      M protein elicits antibodies, that are both opsonic and protective, but which are
      type specific. J14, a chimeric peptide that contains 14 amino acids from the M
      protein conserved C-region at the carboxy-terminus, offers the possibility of a
      vaccine which will elicit protective opsonic antibodies against multiple
      different GAS strains. In this study, we searched for J14 and J14-like sequences
      and the number of their repeats in the C-region of the M protein from GAS strains
      isolated from the Northern Thai population. Then, we examined the bactericidal
      activity of J14, J14.1, J14-R1 and J14-R2 antisera against multiple Thai GAS
      strains. RESULTS: The emm genes of GAS isolates were sequenced and grouped as 14
      different J14-types. The most diversity of J14-types was found in the C1-repeat.
      The J14.1 type was the major sequence in the C2 and C3-repeats. We have shown
      that antisera raised against the M protein conserved C-repeat region peptides,
      J14, J14.1, J14-R1 and J14-R2, commonly found in GAS isolates from the Northern
      Thai population, are able to kill GAS of multiple different emm types derived
      from an endemic area. The mean percent of bactericidal activities for all J14 and
      J14-like peptide antisera against GAS isolates were more than 70%. The mean
      percent of bactericidal activity was highest for J14 antisera followed by J14-R2,
      J14.1 and J14-R1 antisera. CONCLUSION: Our study demonstrated that antisera
      raised against the M protein conserved C-repeat region are able to kill multiple
      different strains of GAS isolated from the Northern Thai population. Therefore,
      the four conserved "J14" peptides have the potential to be used as GAS vaccine
      candidates to prevent streptococcal infections in an endemic area.

PMID- 16895611
TI  - Low grade endometrial stromal sarcoma of uterine corpus, a clinico-pathological
      and survey study in 14 cases.
AB  - BACKGROUND: Endometrial stromal sarcoma (ESS) is a rare disease with probably
      less than 700 new cases in the USA or Europe per year. The aim of this study was
      to evaluate the behavior of low-grade endometrial stromal sarcoma (LGESS) in
      relation to their clinical and pathological features and to identify possible
      prognostic factors. PATIENTS AND METHODS: Fourteen patients with histologically
      proven ESS were included in the analysis. Endometrial stromal sarcoma is
      characterized by proliferations composed of cells with Endometrial stromal cell
      differentiation. Low-grade endometrial stromal sarcoma has an infiltrating margin
      and typically show extensive worm-like vessel invasion. RESULTS: The median age
      was 44.35 +/- 6 years. The most common presenting symptom was vaginal bleeding,
      occurring in twelve patients (86%). Diagnosis was made through Fractional
      dilatation and curettage in four patients (28.5%). Eight patients had a total
      abdominal hysterectomy and salpingo-oophorectomy (57%). Radiotherapy as adjuvant
      therapy was administered to four patients (28.5%). The median follow-up time was
      45.6 months (range 24-84). The median overall survival of the 14 patients was
      45.35 +/- 21 months (range 20-83). Three of 14 patients demonstrated a recurrence
      of disease at 9, 72, and 96 months respectively. The recurrent diseases were
      treated with surgery, chemotherapy, and radiotherapy. No patient died of the
      disease. Clinico-pathological parameters did not significantly differ between
      patients with and without recurrence, but patients with no myometrial invasion
      and low mitotic count < or = 5/HPF showed longer disease-free survival.
      CONCLUSION: Five-year survival rate was 93%. Survival probabilities were
      calculated by the product limit method of Kaplan and Meier that showed, patients
      with no myometrial invasion and low mitotic count < or = 5/HPF have longer
      disease-free survival, but P value was not significant.

PMID- 16895612
TI  - Effectiveness of low-Dye taping for the short-term treatment of plantar heel
      pain: a randomised trial.
AB  - BACKGROUND: Plantar heel pain is one of the most common musculoskeletal disorders
      of the foot and ankle. Treatment of the condition is usually conservative,
      however the effectiveness of many treatments frequently used in clinical
      practice, including supportive taping of the foot, has not been established. We
      performed a participant-blinded randomised trial to assess the effectiveness of
      low-Dye taping, a commonly used short-term treatment for plantar heel pain.
      METHODS: Ninety-two participants with plantar heel pain (mean age 50 +/- 14
      years; mean body mass index 30 +/- 6; and median self-reported duration of
      symptoms 10 months, range of 2 to 240 months) were recruited from the general
      public between February and June 2005. Participants were randomly allocated to
      (i) low-Dye taping and sham ultrasound or (ii) sham ultrasound alone. The
      duration of follow-up for each participant was one week. No participants were
      lost to follow-up. Outcome measures included 'first-step' pain (measured on a 100
      mm Visual Analogue Scale) and the Foot Health Status Questionnaire domains of
      foot pain, foot function and general foot health. RESULTS: Participants treated
      with low-Dye taping reported a small improvement in 'first-step' pain after one
      week of treatment compared to those who did not receive taping. The estimate of
      effect on 'first-step' pain favoured the low-Dye tape (ANCOVA adjusted mean
      difference -12.3 mm; 95% CI -22.4 to -2.2; P = 0.017). There were no other
      statistically significant differences between groups. Thirteen participants in
      the taping group experienced an adverse event however most were mild to moderate
      and short-lived. CONCLUSION: When used for the short-term treatment of plantar
      heel pain, low-Dye taping provides a small improvement in 'first-step' pain
      compared with a sham intervention after a one-week period.

PMID- 16895614
TI  - A survey of the use of 2D ultrasound guidance for insertion of central venous
      catheters by UK consultant paediatric anaesthetists.
AB  - BACKGROUND AND OBJECTIVE: National Institute for Clinical Excellence guidance
      states that 2D imaging ultrasound guidance should be used when inserting internal
      jugular venous lines in adults and children in the elective situation and should
      be considered in most clinical circumstances requiring central venous catheter
      insertion. This survey explored the availability, training and use of ultrasound
      devices by consultant paediatric anaesthetists in the UK. METHODS: A
      questionnaire was distributed to UK members of the Association of Paediatric
      Anaesthetists of Great Britain and Ireland. RESULTS: There was a response rate of
      63% and of those responding, 212 (81%) inserted paediatric central venous
      catheters. Ultrasound devices were available in the workplace of 216 (82%) and
      the average number of devices available per department was two. For elective
      paediatric theatre cases, 26% of paediatric anaesthetists with access to an
      ultrasound device always used it when inserting an internal jugular central
      venous line. The majority (74%) of respondents had received training in the use
      of 2D ultrasound. CONCLUSIONS: National Institute for Clinical Excellence
      guidance on the use of ultrasound locating devices for placing central venous
      catheters is not universally adhered to. Among the reasons for this are problems
      with availability of equipment, lack of training in the use of ultrasound and non
      acceptance of the guidelines.

PMID- 16895615
TI  - Effect of maternal facial oxygen on neonatal behavioural scores during elective
      Caesarean section with spinal anaesthesia.
AB  - BACKGROUND AND OBJECTIVE: For many, the administration of additional oxygen to
      the women receiving regional anaesthesia for Caesarean section is traditional,
      but for others it is controversial because of doubts about its efficacy. The aim
      of our study was to determine if beneficial effects of maternal oxygen therapy on
      the fetus could be revealed using a neonatal behavioural scoring system. METHODS:
      Sixty women with a normal singleton pregnancy beyond 36 weeks gestation,
      undergoing elective Caesarean section under spinal anaesthesia were randomized
      into two groups: Group 1 received air and oxygen mixture through a Hudson style
      face mask (FiO2 of 0.21-0.25). Group 2 received FiO2 of 0.40-0.60 through an
      identical Hudson style face mask. Neurologic Adaptive Capacity Score on all the
      infants within 5 min of birth and between 10 and 24 h after the Caesarean
      delivery was performed. Apgar score, umbilical venous blood oxygen tension and
      umbilical artery standardized base excess were recorded. RESULTS: Initial
      Neurologic Adaptive Capacity Scores at birth in Groups 1 and 2 were 32.6 (SD 4.6)
      and 31.3 (SD 4.3), respectively. Latter scores were 36.0 (SD 3.0) and 36.5 (SD
      1.9), respectively. Neither were statistically significant. There were no
      significant differences between the groups for any of the recorded variables.
      CONCLUSIONS: Administering maternal oxygen using a standard commercial Hudson
      style face mask does not appear to significantly improve oxygen delivery to, nor
      does it influence acidosis or behavioural effects in, the normal neonate at
      elective Caesarean delivery with spinal anaesthesia.

PMID- 16895616
TI  - Liaisons dangereuses? General anaesthetics and long-term toxicity in the CNS.
AB  - We do not know how general anaesthetics cause their desired effects. Contrary to
      what has been thought until relatively recently, the clinical state of
      anaesthesia consists of multiple components that are mediated via interaction of
      the anaesthetic drugs with different targets on the molecular, the cellular, the
      network and the structural-anatomical levels. The mechanisms by which some of
      these drugs induce the different components of "anaesthesia" may be rather
      specific: discrete mutations of single amino acids in specific proteins
      profoundly affect the ability of certain anaesthetics to achieve specific
      endpoints. Despite this potential specificity, inhalational anaesthetics are
      present in the body at very high concentrations during surgical anaesthesia. Due
      to their lipid solubility, general anaesthetics dissolve in every membrane,
      penetrate into organelles and interact with numerous cellular structures in
      multiple ways. A priori, it is therefore not unreasonable to assume that these
      drugs have the potential to cause insidious changes in the body other than those
      acute and readily apparent ones that we routinely monitor for. Some changes may
      wane within a short time after removal of the drug (e.g. the suppression of
      immune cell function). Others may persist after complete removal of the drug and
      even become self-propagating (e.g. spread of malignant cells, the beta
      oligomerization of proteins), still others may be irreversible (e.g. the
      induction of apoptosis in the central nervous system) but of unclear
      significance. This article will focus on evidence for anaesthetic toxicity in the
      central nervous system, which appears to be susceptible to anaesthetic
      neurotoxicity primarily at the extremes of ages but via different pathways: in
      the neonate, during the period of most intense synaptogenesis, anaesthetics can
      induce excessive apoptosis; in the aging brain subtle cognitive dysfunction can
      persist long after clearance of the drug and processes resembling
      neurodegenerative disorders may be accelerated. At all ages, anaesthetics affect
      gene expression regulating protein synthesis in poorly understood ways. While it
      seems reasonable to assume that the vast majority of our patients completely
      restore homeostasis after general anaesthesia, exposure to these drugs probably
      has more profound and longer-lasting effects on the brain than heretofore
      imagined.

PMID- 16895617
TI  - Balanced conscious sedation with intravenous induction and inhalational
      maintenance for patients requiring endoscopic and/or surgical procedures.
AB  - BACKGROUND AND OBJECTIVE: The use of inhalation sedation with sub-anaesthetic
      concentrations of sevoflurane and nitrous oxide mixture is expected to reduce
      amounts of intravenous sedative drugs needed to produce a balanced sedation with
      the benefits of having reduced side-effects. METHODS: Eighty-two patients
      requiring endoscopic and/or surgical procedures under conscious sedation and
      local anaesthesia were recruited for this pilot study. Conscious sedation was
      induced with a titrated dose of midazolam and propofol given intravenously until
      the clinical end-point of conscious sedation was achieved. Subsequently, during
      the procedure, the patient was asked to breathe sevoflurane 0.1-0.3% and a fixed
      ratio of 40% nitrous oxide in oxygen given through a face mask. RESULTS: In 78
      patients (95.1%), the treatment was completed successfully. Patients were
      discharged back to the wards within 4-16 min (10.1) without significant side
      effects. Treatment was satisfactorily accepted by 38 patients (48.7%) and
      considered excellent by 40 patients (51.3%). CONCLUSIONS: The use of titrated
      doses of intravenous sedative drugs for induction of conscious sedation followed
      by the use of low concentrations (0.1-0.3%) of sevoflurane combined with 40%
      nitrous oxide for maintenance of conscious sedation in patients requiring
      endoscopic and/or surgical procedures under local anaesthesia, has the potential
      advantages of reducing amounts of intravenous sedative drugs, less likelihood of
      problems from drug side-effects and fast recovery and discharge time. Further
      investigations to establish the technique are currently in progress.

PMID- 16895613
TI  - Cross genome comparisons of serine proteases in Arabidopsis and rice.
AB  - BACKGROUND: Serine proteases are one of the largest groups of proteolytic enzymes
      found across all kingdoms of life and are associated with several essential
      physiological pathways. The availability of Arabidopsis thaliana and rice (Oryza
      sativa) genome sequences has permitted the identification and comparison of the
      repertoire of serine protease-like proteins in the two plant species. RESULTS:
      Despite the differences in genome sizes between Arabidopsis and rice, we
      identified a very similar number of serine protease-like proteins in the two
      plant species (206 and 222, respectively). Nearly 40% of the above sequences were
      identified as potential orthologues. Atypical members could be identified in the
      plant genomes for Deg, Clp, Lon, rhomboid proteases and species-specific members
      were observed for the highly populated subtilisin and serine carboxypeptidase
      families suggesting multiple lateral gene transfers. DegP proteases, prolyl
      oligopeptidases, Clp proteases and rhomboids share a significantly higher
      percentage orthology between the two genomes indicating substantial evolutionary
      divergence was set prior to speciation. Single domain architectures and
      paralogues for several putative subtilisins, serine carboxypeptidases and
      rhomboids suggest they may have been recruited for additional roles in secondary
      metabolism with spatial and temporal regulation. The analysis reveals some domain
      architectures unique to either or both of the plant species and some inactive
      proteases, like in rhomboids and Clp proteases, which could be involved in
      chaperone function. CONCLUSION: The systematic analysis of the serine protease
      like proteins in the two plant species has provided some insight into the
      possible functional associations of previously uncharacterised serine protease
      like proteins. Further investigation of these aspects may prove beneficial in our
      understanding of similar processes in commercially significant crop plant
      species.

PMID- 16895618
TI  - Acupressure for postoperative nausea and vomiting in gynaecological patients
      receiving patient-controlled analgesia.
AB  - BACKGROUND AND OBJECTIVES: To evaluate the effectiveness of acupressure in
      preventing nausea and vomiting in patients undergoing gynaecological operations
      and receiving a patient-controlled analgesia device. METHODS: Patients aged
      between 40 and 65 yr were included. Exclusion criteria were obesity, diabetes
      mellitus, and history of motion sickness, postoperative nausea and vomiting, or
      smoking. Patients were randomized into one of two groups, acupressure and
      control. In the acupressure group, acupressure bands were placed on both wrists
      with the plastic bead positioned at the P6 point. In controls, beads were placed
      at a non-acupoint site. All patients received a standard general anaesthetic.
      Postoperatively, patients were connected to a patient-controlled analgesia device
      with morphine (loading dose 5 mg, background infusion 1 mg h-1, bolus dose 1 mg
      and lock-out time 10 min). Pain and sedation scores, respiratory rate, heart
      rate, arterial pressure and oxygen saturation were recorded for 24 h.
      Metoclopramide 10 mg was administered intravenously as a rescue antiemetic.
      RESULTS: Fifty patients received acupressure and 50 were controls. In the
      acupressure group, 33% of patients had nausea compared with 63% controls. The
      cumulative incidence of vomiting at 24 h was 25% with acupressure and 61% in
      controls. The incidence of nausea, vomiting and antiemetic use was significantly
      lower with acupressure. CONCLUSIONS: Acupressure at the P6 meridian point is an
      effective alternative for the prevention of nausea and vomiting in patients
      receiving patient-controlled analgesia with morphine after gynaecological
      surgery.

PMID- 16895620
TI  - Comparison of LMA Unique, Ambu laryngeal mask and Soft Seal laryngeal mask during
      routine surgical procedures.
AB  - BACKGROUND AND OBJECTIVE: This study was performed to compare three disposable
      airway devices, the LMA Unique (LMA-U), the Ambu laryngeal mask (Ambu LM) and the
      Soft Seal laryngeal mask (Soft Seal LM) for elective general anaesthesia during
      controlled ventilation in non-paralysed patients. METHODS: One hundred and twenty
      ASA I-III patients scheduled for routine minor obstetric surgery were randomly
      allocated to the LMA-U (n = 40), Ambu LM (n = 40) or Soft Seal LM (n = 40)
      groups, respectively. Patients were comparable with respect to weight and airway
      characteristics. A size 4 LMA was used in all patients and inserted by a single
      experienced anaesthesiologist. Oxygenation, overall success rate, insertion time,
      cuff pressure and resulting airway leak pressure were determined as well as a
      subjective assessment of handling and the incidence of sore throat, dysphagia and
      hoarseness. RESULTS: Time of insertion was shortest with the Ambu LM, while
      failure rates were comparable with the LMA-U, the Ambu LM and the Soft Seal LM
      (median 19 s; range 8-57 s; success rate 100% vs. 14; 8-35; 97% vs. 20; 12-46;
      95%). Insertion was judged 'excellent' in 75% of patients in the LMA-U group, in
      70% of patients in Ambu LM group and in 65% of patients in the Soft Seal LM
      group. There was no difference between devices with respect to postoperative
      airway morbidity at 6 h or 24 h following surgery. CONCLUSIONS: All three
      disposable devices were clinically suitable with respect to insertion times,
      success rates, oxygenation, airway and leak pressures, as well as to subjective
      handling and postoperative airway morbidity.

PMID- 16895621
TI  - Effect of intraoperative intravenous acetaminophen vs. intramuscular meperidine
      on pain and discharge time after paediatric dental restoration.
AB  - BACKGROUND AND OBJECTIVE: Enteral acetaminophen (paracetamol) has limited
      analgesic efficacy due to its delayed absorption and sub-therapeutic plasma
      concentration. Intravenous (i.v.) acetaminophen solves this issue and could thus
      provide adequate analgesia as a single agent. We compared intraoperative i.v.
      acetaminophen with intramuscular (i.m.) meperidine with regard to postoperative
      analgesia and readiness for discharge in paediatric patients undergoing day care
      dental restoration. METHODS: Forty children were randomized, in this double-blind
      study, to receive acetaminophen 15 mg kg-1 i.v. (Group A) or meperidine 1 mg kg-1
      i.m. (Group M) after anaesthesia induction and before surgery. All patients
      received midazolam 0.5 mg kg-1 orally 30 min preoperatively and fentanyl 1 microg
      kg-1 i.v. immediately after induction. Anaesthesia was induced with either
      sevoflurane inhalation or propofol 3 mg kg-1 i.v. and was maintained with
      sevoflurane. Postoperatively, the objective pain scale, Ramsay sedation score,
      and Aldrete score were determined every 5 min until readiness for recovery room
      discharge (defined as achieving an Aldrete score of 10). RESULTS: Group A had
      slightly higher pain scores during early recovery compared with Group M
      (estimated marginal means: 3 +/- SEM 0.4 vs. 2 +/- SEM 0.4, respectively (95% CI
      for difference: 0.4, 2.6), P = 0.012 for F-test). In contrast, Ramsay scores were
      higher in Group M than in Group A during assessment period (estimated marginal
      means: 4 +/- SEM 0.3 vs. 2 +/- SEM 0.4, respectively (95% CI for difference: 
      2.3, -0.3), P = 0.013 for F-test). Group A patients achieved an Aldrete score of
      10 sooner than those in Group M (5 +/- SEM 2 vs. 16 +/- SEM 4 min, respectively
      (95% CI for difference: -9, -14), P = 0.009). CONCLUSION: Compared with i.m.
      meperidine, intraoperative i.v. acetaminophen resulted in slightly higher pain
      scores but earlier readiness for recovery room discharge in paediatric patients
      undergoing dental restoration. The potential economic benefit of early recovery
      room discharge needs to be further explored.

PMID- 16895622
TI  - Doxapram and aminophylline on bispectral index under sevoflurane anaesthesia: a
      comparative study.
AB  - BACKGROUND AND OBJECTIVE: To evaluate and compare the effect of two clinically
      available central nervous system stimulants, namely doxapram and aminophylline on
      arousal from sevoflurane anaesthesia and bispectral index. METHODS: This
      randomized, double-blind, placebo-controlled, prospective study was conducted in
      90 adult females, ASA I-II, scheduled for elective lower abdominal surgeries at
      Taipei Medical University Hospital. At 5 min before the completion of surgery,
      under sevoflurane anaesthesia, patients were divided into three groups to receive
      doxapram 1 mg kg(-1), aminophylline 2 mg kg(-1) or saline placebo intravenous.
      Standard vital signs, end-tidal CO(2), end-expiratory sevoflurane concentration,
      bispectral index and neuromuscular blockade were measured plus clinical
      parameters of recovery from general anaesthesia. RESULTS: Compared with the
      control group, patients receiving doxapram or aminophylline showed a similarly
      faster recovery from sevoflurane anaesthesia correlated with increase in
      bispectral index. CONCLUSION: Intravenous administration of doxapram 1 mg kg(-1)
      or aminophylline 2 mg kg(-1) hastened the early recovery from sevoflurane
      anaesthesia. The arousal effect of aminophylline and doxapram appears to be
      similar.

PMID- 16895623
TI  - Evidence-based follitropin.
AB  - The proper utilization of gonadotrophin during ovarian stimulation is absolutely
      essential and can modify the results (pregnancy rates). Moreover, several
      compounds and preparations are now available for use. This commentary discusses
      those preparations of follitropin (FbM and FbB) and the most relevant
      epidemiological evidence to obtain the best result during ovarian stimulation.

PMID- 16895624
TI  - Further improvement in IVF outcome may need more than consistency in ovarian
      stimulation.
AB  - It is agreed that reliability of hormonal products, starting with recombinant
      technology, has improved uniformity of ovarian response to a specified dosage,
      and that this has resulted in better pregnancy rates. Nevertheless, IVF cycle
      cancellation rate has not experienced a substantial decline in the last 5-10
      years. We feel that further improvement will be more likely to be achieved once
      we gain better understanding of factors intrinsic to oocyte biology, such as
      oocyte ageing and oocyte depletion.

PMID- 16895628
TI  - Aromatase inhibitors in ovarian stimulation for IVF/ICSI: a pilot study.
AB  - This prospective randomized pilot study was aimed at investigating the effect of
      the novel addition of aromatase inhibitors to an ovarian stimulation protocol for
      IVF or intracytoplasmic sperm injection, on endocrine parameters including serum
      androgen, oestrogen, progesterone, LH and FSH concentrations. The patients were
      randomized to receiving letrozole (group A; n = 10), versus no letrozole (group
      B; n = 10) in an ovarian stimulation protocol with recombinant FSH 150 IU/day
      starting on day 2 of the cycle, and gonadotrophin-releasing hormone antagonist
      0.25 mg/day starting on day 6 of the cycle. Median LH concentrations were
      significantly higher (P < 0.01) in group A versus group B during letrozole
      administration. Median serum oestradiol concentrations were lower in group A
      versus group B, and median serum FSH, testosterone and androstenedione
      concentrations were higher in group A versus group B, throughout the follicular
      phase, without reaching significance. Median endometrial thickness was
      significantly higher (P < 0.05) in group A versus group B on the day of human
      chorionic gonadotrophin administration. Pregnancies were achieved. This pilot
      study supports the idea that aromatase inhibitors can contribute to normal
      potential of implantation and follicular response, without having negative anti
      oestrogenic effects.

PMID- 16895627
TI  - IVM--the first choice for IVF in Italy.
AB  - In March 2004, a new law was introduced in Italy to regulate assisted
      reproduction; at present it is impossible to use more than a maximum of three
      oocytes per IVF cycle, nor can embryos or prezygotes (2PN cells) be selected or
      cryopreserved. The prohibitions introduced by the new law have, on the one hand,
      reduced the expectations of success of current techniques and, on the other hand,
      stimulated clinicians and embryologists to work on new therapeutic strategies so
      as to offer the highest chances of success with the lowest risks. In-vitro
      maturation (IVM) of oocytes fits very well with these new requirements: ovarian
      stimulation is avoided and the handling of spare oocytes is facilitated. The IVM
      protocol is an intriguing alternative to conventional IVF techniques, since it
      removes the side-effects of drug stimulation, especially ovarian hyperstimulation
      syndrome, and it also reduces the costs of the entire procedure, both in terms of
      'time consumption' and 'patient/society costs for drugs'. In the authors' IVF
      centre the IVM technique has been used for more than a year, with significant
      success in terms of maturation and fertilization rates, percentage of embryo
      transfers, number of pregnancies and, finally, healthy babies born.

PMID- 16895629
TI  - Rescue of corpus luteum function with peri-ovulatory HCG supplementation in
      IVF/ICSI GnRH antagonist cycles in which ovulation was triggered with a GnRH
      agonist: a pilot study.
AB  - Previous studies found a poor clinical outcome when a GnRH agonist (GnRHa) was
      used to trigger ovulation in GnRH antagonist IVF/ICSI cycles. This study aimed to
      determine the clinical and endocrine effects as well the optimal timing of HCG
      supplementation. Forty-five normogonadotrophic IVF/ICSI patients following a
      flexible antagonist protocol were prospectively randomized (sealed envelopes) to
      triggering of ovulation with a single bolus of either 10,000 IU of HCG (group 1,
      n = 15) or 0.5 mg buserelin s.c. In addition, the GnRHa triggered group was
      randomized into two groups: group 2 (n = 17) was supplemented with HCG 1500 IU,
      12 h after ovulation induction and group 3 (n = 13) was supplemented with HCG
      1500 IU 35 h after ovulation induction. Group 1 and group 3 had significantly
      higher luteal phase concentrations of progesterone (P < 0.001) as compared with
      group 2. Moreover, the clinical pregnancy rate of groups 1 and 3 was similar and
      significantly higher (P < 0.02) than that of group 2. A larger study, however, is
      required to substantiate these differences. No differences were seen regarding
      mid-luteal inhibin A concentrations between the three groups. Triggering of
      ovulation with GnRHa supplemented with 1500 IU HCG 35 h later (group 3) seems to
      secure a normal luteal phase and a normal clinical pregnancy outcome.

PMID- 16895630
TI  - Comparative assessment of the consistency and quality of a highly purified FSH
      extracted from human urine (urofollitropin) and a recombinant human FSH
      (follitropin alpha).
AB  - The revolutionary development of biotechnology-derived therapeutic proteins has
      provided the expected improvements in quality, purity and consistency, as
      demonstrated in recombinant human FSH (rhFSH). However, the development of urine
      derived gonadotrophins has not always shown comparable improvements. More
      recently, highly purified urine-derived FSH (uFSH-HP) products have become widely
      available. The relative purity, level of urine-derived contaminants, and
      consistency of one such highly purified human uFSH (uhFSH) (urofollitropin) has
      been assessed and directly compared with rhFSH (follitropin alpha). It has been
      demonstrated that the highly purified urofollitropin contains variable levels of
      urine-derived contaminant proteins and demonstrates a variable level of FSH
      purity, FSH isoforms, and delivered dose. These variable factors may contribute
      to the control of ovarian stimulation. The relative purity, variable consistency
      and the presence of contaminants indicates that the urofollitropin is, at best, a
      partially purified uFSH that is not able to meet the quality attributes of
      follitropin alpha (rhFSH).

PMID- 16895631
TI  - Use of metformin for prevention of ovarian hyperstimulation syndrome: a novel
      approach.
AB  - In the present study, which includes 287 participants, metformin has been used by
      women undergoing IVF/intracytoplasmic sperm injection for more than 5 weeks
      before and during treatment and during luteal phase. There was no significant
      difference in number of gonadotrophins used, days of stimulation, number of
      oocytes retrieved, and number of embryos replaced. There was no significant
      difference in clinical pregnancy rate between both groups but there was
      significant reduction in the incidence of ovarian hyperstimulation syndrome
      (OHSS) in the group taking metformin. Metformin is a safe, cheap drug that can
      help in prevention of OHSS.

PMID- 16895632
TI  - Substituting HCG with GnRH agonist to trigger final follicular maturation--a
      retrospective comparison of three different ovarian stimulation protocols.
AB  - The study retrospectively evaluated the influence of triggering final oocyte
      maturation with gonadotrophin-releasing hormone (GnRH) agonist on the outcome of
      IVF cycles. Four hundred and sixty consecutive women admitted to the IVF unit
      during a 4-year period were enrolled in the study. Ovarian stimulation
      characteristics and clinical pregnancy rate were compared between three groups:
      patients at risk of developing ovarian hyperstimulation syndrome (OHSS),
      undergoing either the long GnRH-agonist protocol (agonist group) or the flexible
      multidose GnRH-antagonist protocol who received GnRH-agonist for final oocyte
      maturation (antagonist-agonist group); and patients not at risk of developing
      severe OHSS undergoing the flexible multidose GnRH-antagonist protocol who
      received human chorionic gonadotrophin (HCG) for final oocyte maturation
      (antagonist-HCG group). Implantation and clinical pregnancy rates were lowest in
      the antagonist-agonist group despite the fact that no difference were was
      observed in fertilization rates between the groups. Moreover, the high-responder
      antagonist-agonist group required shorter stimulation and had higher numbers of
      oocytes retrieved as compared with the high-responder agonist-group. No case of
      severe OHSS was observed in the antagonist-agonist group. The use of flexible
      multidose GnRH-antagonist protocol with GnRH-agonist for final oocyte maturation,
      in high-responder patients, eliminates the risk of OHSS but results in decreased
      implantation and pregnancy rates.

PMID- 16895633
TI  - Comparative concentrations of steroid hormones and proteins in human peri
      ovulatory peritoneal and follicular fluids.
AB  - Despite the fact that both peritoneal (PF) and follicular (FF) fluids have a
      common ovarian origin, FF is a natural inducer of sperm acrosome reaction (AR)
      while PF is not. To better understand these effects, concentrations of
      oestradiol, progesterone and proteins in peri-ovulatory PF and FF were determined
      and compared. PF was aspirated by laparoscopy at the peri-ovulatory stage from
      women with unexplained infertility. FF was collected from patients undergoing IVF
      and pooled. PF and FF were tested for the presence of antisperm antibodies.
      Oestradiol and progesterone were measured by enzyme immunoassay, and total
      protein concentration was determined and analysed. The AR was determined in
      spermatozoa that were exposed to PF alone, progesterone-supplemented PF,
      progesterone, control medium, or ethanol. No antisperm antibodies were found in
      any fluid tested. Oestradiol and progesterone and concentrations in PF were
      significantly lower than in FF. Protein concentration was also significantly
      lower in PF than in FF, but no differences were observed between the
      electrophoretic patterns. When capacitated spermatozoa were exposed to
      progesterone-supplemented PF there was a significant increase in the percentage
      of AR with respect to those in PF, control medium or ethanol. These results
      suggest that the lack of AR-stimulating activity of PF was related to its lower
      progesterone concentration compared with FF.

PMID- 16895634
TI  - Letrozole versus human menopausal gonadotrophin in women undergoing intrauterine
      insemination.
AB  - This pilot study was conducted to compare the results of intrauterine
      insemination (IUI) under ovarian stimulation with either letrozole (Femara) or
      human menopausal gonadotrophin (HMG). A randomized controlled trial was
      conducted. Eighty women aged 20-35 years with unexplained infertility of at least
      2 years' duration were randomized according to a computer-generated randomization
      list into the letrozole group and the HMG group. Letrozole was administered at 5
      mg/day from day 3 to day 7 of the IUI cycle. HMG injections were started on day 3
      at a dose of 75 IU for women under 30 years old and 150 IU for women over 30
      years old and monitored periodically by vaginal ultrasound and oestradiol
      concentrations. The variables selected for analysis were clinical pregnancy rate,
      endometrial thickness, length of follicular phase and number of preovulatory
      follicles. No statistically significant difference in clinical pregnancy rates
      per cycle was found for patients in the letrozole or HMG group (18.4 versus
      15.7%). Cost was significantly higher in the HMG stimulation cases (P < 0.001)
      and no injections were required in the letrozole group. In conclusion, letrozole
      offers a new treatment regimen in ovarian stimulation regimens for IUI that is
      cost effective, simple and convenient for the patients.

PMID- 16895635
TI  - Interactions of the meiotic spindle with mitotic chromosomes in GV mouse oocytes.
AB  - During mitosis, a spindle checkpoint detects chromosome misalignment and halts
      the cell cycle progression. In meiosis of female germ cells, however, it is
      debatable whether such a checkpoint is present. This research employed a unique
      model in the mouse, mitotic chromosomes transferred to meiotic cytoplasts to
      investigate whether a meiotic oocyte's microtubule apparatus can effectively
      separate mitotic metaphase chromosomes, and whether a spindle checkpoint exists
      during its division. The intact germinal vesicle (GV) oocytes, enucleated GV
      cytoplasts, and enucleated GV cytoplasts at 15 h in-vitro maturation were
      transferred with a metaphase fibroblast cell. When mitotic chromosomes were
      transferred into enucleated or intact mouse GV oocytes, the first bipolar meiotic
      spindles were established and the reconstructed oocytes were able to extrude
      polar bodies. However, none of the reconstructed oocytes showed complete and
      accurate alignment of chromosomes, except the enucleated GV cytoplasts
      reconstructed after maturation. The spindle formation and polar body extrusion
      suggest that the first meiotic spindle was functional, and the chromosome
      misalignment did not prevent the onset of anaphase. The data indicate that a
      spindle checkpoint, providing surveillance of misaligned chromosomes, was
      overridden or compromised by the incompatibility between somatic chromosomes and
      meiotic spindles during the first meiotic division.

PMID- 16895636
TI  - Cryopreservation of unfertilized human oocytes.
AB  - Previous investigations revealed that choline-based freezing media developed in
      our laboratory were superior to conventional sodium-based media for storing mouse
      oocytes. This paper examines the ability of the choline-based medium CJ2 and a
      modified form of this medium, CJ3, to cryopreserve unfertilized human oocytes.
      Oocytes that were consented for research and matured overnight, as well as
      freshly collected, donor, mature metaphase II (MII) oocytes, were cryopreserved
      using choline-based media and an optimized slow-cooling protocol. The results
      showed higher survival and fertilization rates when CJ3 supplemented with 0.2
      mmol/l sucrose was used as compared with CJ2 supplemented with either 0.1 mmol/l
      or 0.2 mmol/l sucrose. Freshly collected oocytes were more difficult to
      cryopreserve than those matured in vitro. Modification of the base medium proved
      to be one of the key factors in obtaining survival rates over 90%. Fertilization
      rates, embryo development, and genetic analysis of embryos resulting from control
      and frozen-thawed oocytes are provided. There appears to be a high correlation
      between chromosomal anomalies and abnormal morphology in embryos from thawed
      oocytes.

PMID- 16895638
TI  - Effective method for in-vitro culture of cryopreserved human ovarian tissue.
AB  - It is widely accepted that it is possible to successfully cryopreserve human
      ovarian tissue by direct plunging into liquid nitrogen using permeable
      cryoprotectants only, without disaccharides. This study aimed to search for and
      test a new method for in-vitro culture of vitrified tissue. Ovarian biopsies were
      obtained during operative laparoscopy. Pieces of ovarian tissue were vitrified
      and warmed. After warming, tissue pieces were randomly distributed into three
      groups for further culture: in 2 ml of culture medium which was regularly renewed
      (group 1), in 30 ml of culture medium without agitation (group 2) and in 30 ml of
      culture medium with agitation (group 3). During the 2-week and 6-week culture,
      the growth of follicles within the vitrified-warmed ovarian tissue pieces was
      investigated. After 2 weeks of culture, mean numbers of non-degenerated follicles
      per mm(2) of tissue were 1.5, 1.7 and 4.5 for groups 1, 2 and 3 respectively
      (groups 1 and 2 versus group 3, P < 0.05). Agitation during culture of ovarian
      tissue is beneficial, and can be used as a prognostic tool for future warming and
      autotransplantation of ovarian tissue.

PMID- 16895639
TI  - Effect of an oral contraceptive pill on follicular development in IVF/ICSI
      patients receiving a GnRH antagonist: a randomized study.
AB  - This randomized controlled study compared the effectiveness of a gonadotrophin
      releasing hormone (GnRH) antagonist protocol with or without oral contraceptive
      (OC) pretreatment on the number of oocytes retrieved in IVF or intracytoplasmic
      sperm injection (ICSI) patients. Sixty-four patients were randomized to start
      recombinant human FSH (r-hFSH) on day 2 or 3 after OC withdrawal (OC group) or on
      day 2 of a natural cycle (control group). From stimulation day 6 onwards, all
      patients were treated with daily (0.5 mg/ml) GnRH antagonist (Antide). OC
      pretreatment resulted in significantly lower starting concentrations of FSH, LH
      and oestradiol (P < 0.001) and a thinner endometrium (P < 0.0001). In the early
      stimulation period, fewer large follicles were found after OC pretreatment,
      leading to a significantly extended stimulation period (11.6 versus 8.7 days, P <
      0.0001) with more follicles on the day of recombinant human chorionic
      gonadotrophin administration (15.4 versus 12.5, P = 0.02) and more oocytes
      retrieved (13.5 versus 10.2, P < 0.001) as compared with the control group. GnRH
      antagonist regimen, pretreated with OC, prevented the early endogenous FSH rise
      and improved follicular homogeneity, resulting in more oocytes. As a consequence
      of the extended treatment period, more rhFSH was required.

PMID- 16895640
TI  - High-polarized (Delta Psi m(HIGH)) mitochondria are spatially polarized in human
      oocytes and early embryos in stable subplasmalemmal domains: developmental
      significance and the concept of vanguard mitochondria.
AB  - The spatial specificity and stability of subplasmalemmal domains of high
      polarized mitochondria (Delta Psi m(HIGH)) in human oocytes and cleavage stage
      embryos were investigated in instances where changes in
      pericortical/subplasmalemmal organization resulted in the corresponding cytoplasm
      becoming translucent and largely devoid of mitochondria, either by experimental
      manipulation or as a result of spontaneous, stage-specific morphodynamic
      processes. The developmental significance of high-polarized mitochondria was
      examined in early embryos where their loss from a cell(s) occurred by elimination
      into a focal cluster of small extracellular fragments, or by disproportionate
      segregation between blastomeres. The findings demonstrate that pronounced changes
      in the organization of the pericortical and subplasmalemmal cytoplasm do not
      affect these domains, and their displacement under experimental conditions is
      fully reversible. By contrast, in instances of their significant or complete
      elimination, the domains of high-polarized mitochondria did not reform and the
      affected cell(s) remained intact and undivided during culture. The findings (i)
      support a spatial specificity and stability for high-polarized mitochondria,
      which in human oocytes and early embryos, represent a very small fraction of the
      total mitochondrial complement, and (ii) are discussed with respect to their
      suggested participation in transmembrane and signal transduction processes. It is
      proposed that Delta Psi(HIGH) mitochondria located in subplasmalemmal domains are
      'vanguard' organelles that can sense and respond to regulatory signals of
      extrinsic and intrinsic origin during early development.

PMID- 16895643
TI  - Effects of assisted hatching method and age on implantation rates of IVF and
      ICSI.
AB  - The objective of this study was to investigate whether a change in assisted
      hatching (AH) technique from total to partial penetration of the zona pellucida
      improved the outcome of IVF and intracytoplasmic sperm injection cycles where AH
      was indicated. This was an observational study conducted from the beginning of
      January 2000 to the end of April 2005. Total AH was performed in 312 cycles,
      while partial AH was performed in 592 cycles. In women of all ages, implantation,
      clinical pregnancy and live birth rates were higher in the partial AH group than
      in the total AH group (12.6 versus 7.2%, P = 0.0001; 22.3 versus 15.7%, P = 0.02;
      18.2 versus 12.5%, P = 0.03 respectively). The benefit of partial AH was most
      marked in women under 38 years old (i.e. the recurrent implantation failure
      group). The authors conclude that partial AH is associated with higher
      implantation and pregnancy rates than total AH, especially in women under 38
      years old who suffer from recurrent implantation failure.

PMID- 16895641
TI  - Impact of the assessment of early cleavage in a single embryo transfer policy.
AB  - The policy of single embryo transfer (SET) adopted for women <36 years old since
      1 July 2003, strongly calls for improvement of embryo selection. A total of 196
      cycles in which SET was performed were randomly allocated to two groups. In the
      first group, early cleavage was assessed (ECA) 25 h after insemination. The
      embryo with the best score that cleaved early, if present, was selected for
      transfer. In the second group, early cleavage was not assessed (ECNA) and embryo
      selection was based solely on the embryo score. Ninety-eight cycles were
      allocated in the ECA and ECNA group respectively. Early cleavage occurred in 64%
      of cycles and 32.2% of embryos. Patient population and embryo morphology were
      similar between the two groups, and similar delivery rates were observed (27.6
      versus 24.5% respectively in the ECA and ECNA groups). The assessment of early
      cleavage as additional parameter did not improve the delivery rate in the single
      embryo transfer policy.

PMID- 16895645
TI  - Flushing the endometrium prior to the embryo transfer does not affect the
      pregnancy rate.
AB  - This study aimed to determine whether direct flushing of endometrial cavity with
      culture media just after cervical irrigation at the time of embryo transfer has
      any effect on pregnancy rates. A total of 240 women were prospectively
      randomised; one group of patients (group 1) underwent intrauterine direct
      flushing of endometrial cavity with culture media just after cervical irrigation
      at the time of embryo transfer as detected by transabdominal ultrasound and the
      other group of patients (group 2) had cervical flushing but did not undergo
      intrauterine flushing. Pregnancy (positive human chorionic gonadotrophin) rates
      were 57.5% and 62.9% for group 1 and group 2, respectively. Clinical pregnancy
      (positive fetal heart rate) rates were 45.2% and 51.4% for group 1 and group 2,
      respectively. Implantation rates were 20.0% and 21.2% for group 1 and group 2,
      respectively. Ongoing pregnancy (>12 weeks of pregnancy) rates were 47.9% and
      47.2% for group 1 and group 2, respectively. There were no significant
      differences in pregnancy rates, clinical pregnancy rates, implantation rates and
      ongoing pregnancy rates between the two groups. In conclusion, even direct
      flushing of media into the uterine cavity neither improves nor adversely affects
      the pregnancy rate.

PMID- 16895646
TI  - Secretion of soluble HLA-G by day 3 human embryos associated with higher
      pregnancy and implantation rates: assay of culture media using a new ELISA kit.
AB  - Identification of chemical markers in human embryo culture media that relate to
      embryo quality and implantation potential could be an invaluable tool in embryo
      selection for transfer. Embryonic secretion of soluble human leukocyte antigen G
      (sHLA-G) has been postulated to be a marker for 'embryonic competence'. This
      study examines sHLA-G concentrations in day 3 culture media droplets of embryos
      that were selected for transfer, as well as those being cryopreserved. A total of
      712 embryo culture supernatants from 83 patients were assayed. Soluble HLA-G was
      detected in 306 of the 712 samples tested. In the 58 transfers in which at least
      one embryo selected for embryo transfer was positive for sHLA-G, the pregnancy
      rate was 64% (37/58) and the implantation rate per embryo transferred was 38%. In
      contrast, patients receiving only embryos that were negative for sHLA-G had both
      a lower pregnancy rate of 36% (9/25; P < 0.05) and a decreased implantation rate
      (19%; P < 0.05). Expression of sHLA-G was also related to increasing cell stage.
      Concentration of sHLA-G in embryo culture media was variable and in the low range
      (3-10 ng/ml). These data suggest an association between implantation potential
      and embryonic secretion of sHLA-G. The commercial assay kit utilized allowed for
      same day assessment of sHLA-G secretion. Addition of sHLA-G status to traditional
      morphological criteria may be useful as a clinical tool for embryo selection.

PMID- 16895647
TI  - Analysis of an epigenetic argument against human reproductive cloning.
AB  - Human reproductive cloning is a much disputed ethical issue. This technology is
      often condemned as being contrary to human dignity. However, there are also risk
      arguments. An ethical argument that is often put forward by scientists but seldom
      developed in more detail focuses on health risks in animal cloning. There is a
      high risk that animal clones exhibit abnormalities and these are increasingly
      believed to be due to errors in epigenetic reprogramming. The argument is that
      human reproductive cloning should not be carried out because human clones are
      also likely to exhibit abnormalities due to inappropriate epigenetic
      reprogramming. Different versions of this epigenetic argument are analysed, a
      categorical version and a non-categorical. The non-categorical version is
      suggested to be more well-considered. With regard to policy making on human
      reproductive cloning, the categorical version can be used to prescribe a
      permanent ban, while the non-categorical version can be used to prescribe a
      temporary ban. The implications of the precautionary principle--as interpreted in
      the European Union--are investigated. The conclusion is that it seems possible to
      support a temporary ban by reference to this principle.

PMID- 16895648
TI  - In-vitro developmental potential of individual mouse blastomeres cultured with
      and without zona pellucida: future implications for human assisted reproduction.
AB  - This study was designed to compare the developmental potential of individual
      blastomeres derived from 2-, 4-, 6- and 8-cell mouse embryos cultured with and
      without zona pellucida (ZP). In the first series, one, three, five and seven
      blastomeres were biopsied from 2-, 4-, 6- and 8-cell embryos respectively, and
      inserted individually into empty ZP recipients, leaving the remaining blastomere
      within its original ZP. In the second series, the same protocol was used except
      that the biopsied blastomeres were cultured without ZP and compared with the
      remaining blastomere within its original ZP. For the first series, individual
      blastomeres derived from 2-, 4-, 6- and 8-cell embryos cultured with ZP showed
      blastocyst development of 82.4, 68.6, 44.4 and 23.1% respectively, with
      corresponding hatching rates of 70.6, 60.0, 25.9 and 7.7%. For the second series,
      individual blastomeres cultured without ZP progressed with blastocyst development
      of 73.3, 64.5, 35.7 and 22.7% respectively. Blastocyst multiplication was
      achieved most efficiently when using individual blastomeres from 4- and 6-cell
      embryos. This is the first report on comparative in-vitro propagation of single
      blastomeres derived from various cleavage stages in a mammalian species.
      Blastomere cloning with its multiple applications may be envisaged for human
      assisted reproductive technologies.

PMID- 16895649
TI  - Unsuccessful derivation of human embryonic stem cell lines from pairs of human
      blastomeres.
AB  - Human embryonic stem cells (hESC) that differentiate into all three primordial
      germ layers have been established. Differentiation of these cells into desirable
      lineages offers hope for future transplantation therapies. Currently, hESC lines
      are derived from the inner cell mass (ICM) of blastocysts, leading to destruction
      of the embryo, and thus the process is ethically controversial. Successful
      attempts at deriving hESC lines from blastomeres without destruction of the
      ensuing embryo have not been reported. One or two blastomeres are routinely
      biopsied from 8-cell embryos for preimplantation genetic diagnosis. In this study
      it was therefore attempted to derive hESC lines from paired blastomeres. Of 66
      pairs of 8-cell stage blastomeres, four pairs produced two morula and two
      blastocyst-like structures. When plated on mitomycin-C-treated mouse embryonic
      fibroblasts, one morula and one blastocyst-like structure separately produced
      small colonies containing hESC-like cells with prominent nucleoli and high
      nuclear-cytoplasmic ratios. When these colonies were detached and plated onto
      fresh feeders, there was no further colony formation or ensuing hESC lines. The
      results showed that it might not be possible to derive hESC lines directly from
      paired blastomeres. A minimum number of blastomeres in close contact with one
      another may be required to successfully generate an hESC line as blastomeres,
      like ICM and hESC cells, may be 'social' cells.

PMID- 16895650
TI  - Donation of fresh oocytes for nuclear transfer research--a new approach.

PMID- 16895651
TI  - Varicella zoster virus: out of Africa and into the research laboratory.
AB  - This review updates on numerous topics relating to the evolutionary origins of
      varicella zoster virus (VZV), the replication cycle, virion assembly and the
      recent genomic analyses. VZV is one of eight human herpesviruses that have
      existed for at least 400 million years. It has co-evolved with humankind and is
      present in all nationalities globally. The pathogenesis of varicella (chickenpox)
      is dependent on viral replication and dispersion through the body in T
      lymphocytes. VZV replication is similar to that of herpes simplex virus. A
      complete analysis of VZV transcripts has identified their relative abundance,
      with transcripts for the regulatory proteins (open reading frame) ORF62 and ORF63
      among the greatest. Studies of virion assembly have shown that endocytosis
      pathways are involved in the envelopment process by the viral glycoproteins. The
      complete sequencing of five VZV strains has identified numerous single nucleotide
      polymorphisms, and in turn, VZV strains have been segregated into European/North
      American and Asian clades. Furthermore, a small number of mutant VZV strains have
      been identified. These results suggest more diversity between VZV strains than
      previously recognized.

PMID- 16895652
TI  - Editorial: herpes simplex virus and toll-like receptors.

PMID- 16895653
TI  - Toll-like receptors, innate immunity and HSV pathogenesis.
AB  - In the last decade, substantial progress has been made in understanding the
      molecular mechanisms involved in initial host responses to viral infections, and
      how viral recognition leads to the innate responses that ultimately shape the
      adaptive immune response. Viruses, including herpes simplex virus (HSV) types 1
      and 2, trigger toll-like receptors (TLRs) that elicit cytokine and chemokine
      production. In turn, this can create local resistance and modulate T- and B-cell
      mediated immunity. TLR activation by HSV-produced molecules (or other synthetic
      agonists) leads to the remodelling of draining lymph nodes. This enhances the
      screening of naive T-cells, from which antigen-specific lymphocytes can be
      selected and expanded. The innate response thereby serves to direct a timely and
      effective acquired immune response, through the initial TLR recognition of viral
      pathogen-associated molecular patterns that can limit or possibly exacerbate
      viral pathogenesis. Recently, these findings have been exploited by strategies
      that utilize synthetic TLR agonists as prophylactic or therapeutic devices. Such
      devices prime innate immune responses, enhancing host resistance to viral
      infections, including experimental HSV infections.

PMID- 16895654
TI  - Defining a role for antiviral drugs in the treatment of persons with HHV-8
      infection.
AB  - Human herpesvirus type 8 (HHV-8) is the most recently identified member of the
      human herpesvirus family and the aetiological agent of Kaposi's sarcoma, primary
      effusion lymphoma and multicentric Castleman's disease. While highly active
      antiretroviral therapy has led to impressive declines in the incidence of
      Kaposi's sarcoma, HHV-8- associated infections remain common and morbid across
      the globe. Although comprehensive clinical trials of therapy for HHV-8-associated
      infections are lacking, numerous studies have found current treatment modalities
      to be ineffective for many patients. A growing body of basic scientific and
      clinical work suggests that antiviral drugs may have a role in the treatment and
      (more significantly) in the prevention of HHV-8-associated infections. This
      review discusses current evidence for the efficacy of antivirals against HHV-8
      and proposes novel uses for such medications in HHV-8 treatment.

PMID- 16895656
TI  - Adolescents anticipated experience of screening for genital herpes.
AB  - Screening asymptomatic adolescents for genital herpes will require sensitivity to
      adolescents' developmental needs. Twenty-four adolescents (age range 1619 years)
      were interviewed to explore their perceptions of screening. In general,
      adolescents thought screening for genital herpes would be viewed as taking care
      of themselves, although there were concerns that their peers might view getting
      screened as implying that the adolescent was infected or sexually promiscuous.
      Most adolescents expected their parents to respond positively, but typically
      thought that younger adolescents should obtain parental consent for screening,
      and that adolescents should inform their parents of positive test results.
      Adolescents wanted to be screened in settings that provided confidentiality and
      by non-judgemental care providers, but they differed on the setting which they
      believed would accomplish this. Some recommended mass screening (for example,
      screening all of those in a certain year at school), presumably as a way to
      reduce embarrassment and/or stigma. Screening programmes that are adolescent
      friendly and accessible, and address adolescents' specific concerns regarding
      managing the information, can be created.

PMID- 16895657
TI  - New approaches to the therapy of HSV infections.
AB  - Two recent studies have demonstrated single-day regimens of high-dose antiviral
      therapy (famciclovir 1000 mg twice daily for genital herpes, and famciclovir 1500
      mg single dose for herpes labialis) to be effective episodic treatment
      strategies. Both have the potential to improve patient compliance and therapeutic
      satisfaction. Patient-initiated episodic therapy (PIE) regimens such as these may
      improve the time to treatment initiation, which can halt lesion development: PIE
      allows antiviral drugs to be administered in the narrow therapeutic window that
      occurs early in the course of a herpes simplex virus (HSV) infection episode.
      This review article discusses short-course antiviral therapy, which may offer an
      effective alternative to traditional episodic or suppressive antiviral regimens
      for HSV-related disease outbreaks.

PMID- 16895658
TI  - [From Nephrology to nephrology & Therapeutics].

PMID- 16895662
TI  - [The new French rules for the attribution of renal transplants].
AB  - The French rules for the attribution of a kidney transplant are regularly
      evaluated and modified according to scientific progress, evolution of the waiting
      list and of health policies. Modifications, initiated by the Transplantation
      Commission of the French-speaking Society of Nephrology, have been introduced in
      2004 by the Etablissement francais des Greffes and aim at decreasing the number
      of patients on the waiting list having difficult access to transplantation
      because of their immunogenetic characteristics (rare ABO or HLA group, HLA
      immunization). Four points are concerned: 1/ better definition of
      hyperimmunisation; 2/ introduction of a program based on "acceptable mismatches"
      as a new priority for hyperimmunized patients; 3/ suppression of the full-match
      priority to non-immunized patients; 4/ attribution to immunized patients (anti
      HLA antibodies=5-80%) who have difficult access to a transplant, of priorities
      similar to those followed for hyperimmunized patients. This article presents the
      new rules for the allocation of a kidney transplant and the rationale for the
      current modifications.

PMID- 16895663
TI  - [Biocompatibility of peritoneal dialysis fluids].
AB  - Repeated and long-term exposure to conventional glucose-based peritoneal dialysis
      fluids (PDFs) with poor biocompatibility plays a central role in the pathogenesis
      of the functional and structural changes of the peritoneal membrane. We have used
      immortalized human peritoneal mesothelial cells in culture to assess in vitro the
      biocompatibility of PDFs. Low pH, high glucose concentration and heat
      sterilization represent major factors of low biocompatibility. Two recent groups
      of glucose derivatives have been described. Glucose degradation products (GDPs)
      are formed during heat sterilization (glycoxidation) and storage. GDPs can bind
      protein and form AGEs (Advanced Glycation End-products), which can also result
      from the binding of glucose to free NH2 residues of proteins (glycation). The
      physiological pH, and the separation of glucose during heat sterilization (low
      GDP content) in the most recent PDFs dramatically increase the biocompatibility.
      The choice of PD programs with high biocompatibility PDFs allows preserving the
      function of the peritoneal membrane. Improvement of PDF biocompatibility may
      limit the occurrence of chronic chemical peritonitis and may allow long-term PD
      treatment.

PMID- 16895664
TI  - [Cancer and immunosuppression: pro- and antitumoral effects of immunosuppressive
      drugs].
AB  - Malignancies are an important cause of morbidity and mortality among transplant
      patients. Tumor genesis is the consequence of non-specific immunosuppression that
      enhanced oncogenic virus replication, but may also be due to direct effects of
      immunosuppressants. Steroids are believed not to be involved in cancer genesis,
      in contrast to azathioprine, well known to reduce DNA repair ability,
      particularly in skin cells exposed to UV irradiation. Calcineurin inhibitors,
      cyclosporine and tacrolimus, are involved in tumor development through various
      mechanisms: they promote B-cell proliferation by increasing T lymphocyte IL6
      secretion, decrease DNA repair ability and may be able to promote metastasis
      spreading by a direct cellular effect that is independent of their effect on the
      host's immune cells. In vitro anti-tumoral properties of mycophenolate mofetil
      have not been valided in animal models or in human. The last developed
      immunosuppressant mTOR inhibitors, sirolimus and everolimus, effectively control
      the proliferation of various tumor cell lines, promote tumor cell apoptosis and
      inhibit metastatic tumor growth and angiogenesis in in vivo mouse models by
      affecting VEGF production and effect. If these antitumoral features are confirmed
      in human, this new immunosuppressive family will offer the unique opportunity to
      reduce both the incidence of rejection and cancer in organ transplant recipients.

PMID- 16895665
TI  - [Effects of anxiety and depression on haemodialysis adequacy].
AB  - Depression and anxiety are the most commonly encountered psychological problems
      in patients with end-stage renal disease, especially those on renal replacement
      therapy. We sought to assess the prevalence of anxiety and depressive symptoms in
      patients undergoing haemodialysis treatment and to establish the relationship
      between these psychological problems and criteria of haemodialysis adequacy.
      METHODS: We implemented a transversal study on 93 adult haemodialysis patients
      recruited from in Ibn-Sina Haemodialysis department in Rabat in April 2003. They
      underwent three tests performed by a psychiatrist. The first one was the brief
      psychiatric rating scale (BPRS) and then Hamilton anxiety and depression rating
      scales. We also studied anthropometric features, comorbidity, dialysis session's
      characteristics, and the following haemodialysis adequacy parameters:
      extracellular volume, nitrogenous retention, nutritional status, phosphocalcic
      balance, serum potassium, acid-basic equilibrium, anaemia, and inflammatory
      markers. RESULTS: The mean (+/-SD) age of our population was 42+/-15.5. The sex
      ratio was 1.11 (49 W/44 M). Only one patient had a history of psychological care
      by a psychiatrist. The prevalence of depression and anxiety among the patients
      surveyed was 67 and 69.3% respectively. Seven patients had a severe depression.
      We did not found any other psychological condition by BPRS. Depression has been
      shown to be associated to several haemodialysis adequacy markers like high blood
      pressure, interdialytic weight intake, nutritional parameters (serum albumin
      concentration...), and serum creatinin concentration. Depression was more
      frequent in women, diabetics, and patients with C hepatitis. CONCLUSION: This
      study will be continued by a prospective screening of patients under appropriate
      therapy.

PMID- 16895666
TI  - [Transfer from chronic haemodialysis to peritoneal dialysis].
AB  - Peritoneal dialysis patients are frequently transferred from peritoneal dialysis
      to haemodialysis. In contrary transfer from chronic haemodialysis to peritoneal
      dialysis is rare. The aim of this study is to describe the main characteristics
      and the outcome of the dialysis patients transferred from haemodialysis to
      peritoneal dialysis. We retrospectively analyzed the files of 25 patients treated
      by haemodialysis for more than 3 months between 1992 and 2002 and subsequently
      transferred on peritoneal dialysis. Technique survival was 56% at 1 year and 40%
      at two years in haemodialysis. Technique survival was lower in the group starting
      haemodialysis in emergency compared with the group of patients who did not need
      emergent haemodialysis (33 vs 77% at 1 year, P<0.05). The reasons for transfer
      from haemodialysis to peritoneal were vascular access problems (13/25),
      cardiovascular problems (7/25), and patient's choice (5/25). Automated peritoneal
      dialysis was used in 9 cases and continuous ambulatory peritoneal dialysis in 16
      cases. In 13 cases peritoneal dialysis was performed by a home care nurse. At the
      initiation of peritoneal dialysis the mean age was 58+/-18 years, the mean
      Charlson's comorbidity score was 6.1+/-2.5 and 15 patients had a cardiovascular
      disease. The median time on peritoneal dialysis was 5.2 months. During the time
      on peritoneal dialysis sixteen patients presented at least one complication
      related to peritoneal dialysis. In addition fourteen patients were hospitalized
      for a reason which was not associated with peritoneal dialysis. Survival on
      peritoneal dialysis was 61% at six months and 35% at one year. In conclusion, in
      our study, patients transferred from haemodialysis to peritoneal dialysis have
      had a poor outcome on peritoneal dialysis. However, these patients presented
      numerous comorbid conditions at peritoneal dialysis initiation which could
      explain the poor outcome on peritoneal dialysis.

PMID- 16895667
TI  - [Fluoroquinolone induced acute renal failure. General review about a case report
      with crystalluria due to ciprofloxacin].
AB  - A 58 year-old woman developed an acute renal failure very quickly after ingestion
      of two 500 mg tablets of ciprofloxacin, without any other identifiable risk
      factor. Renal biopsy was performed. No sign of acute interstitial nephritis was
      observed but tubular lesions were found, accompanied by deposits of a brown
      yellowish substance identified by infrared microscopy as a ciprofloxacin salt.
      The outcome was favourable. This observation gives the opportunity to remind the
      different forms of quinolone-induced renal injury and to discuss the possible
      ways for preventing renal side-effects related to the quinolone use.

PMID- 16895668
TI  - [Renin-secreting tumour: about a new diagnosed case during pregnancy].
AB  - A 29 year-old female patient developed severe arterial hypertension in the
      beginning of her second pregnancy. Investigations performed at 16 weeks of
      amenorrhea showed hypokaliemia in relation to severe hyperreninism: plasma active
      renin was 25 fold normal value, 94% as prorenin (prorenin representing 94% of
      total renin). Radiological investigations including ultrasonography and MRI
      disclosed an homogenous and avascular tumor in the right kidney. Its ablation
      confirmed renin tumor, and allowed recovery from HTA and continuation of
      pregnancy. This is the 75th reported case in the literature, enabling to make a
      new statement about diagnostic and therapeutic procedures, which are modified
      during pregnancy by contra-indication to X-rays and renin-angiotensin-aldosteron
      axis inhibitors.

PMID- 16895669
TI  - [Congenital and infantile nephrotic syndrome].
AB  - Congenital nephrotic syndrome is present at birth or appears during the first
      three months of life and infantile nephrotic syndrome during the first year.
      Finnish type congenital nephrotic syndrome is an autosomal recessive disease.
      Nephrotic syndrome is present at birth, severe and does not respond to therapy.
      Infectious and nutritional complications are frequent. Renal function
      deteriorates necessitating a dialysis-transplantation program. Between age five
      and eight. The disease does not recur after transplantation. Diffuse mesangial
      sclerosis is the second cause of congenital and infantile nephrotic syndrome. It
      may be isolated or part of a Denys-Drash syndrome (association of the nephropathy
      with male pseudohermaphroditism and Wilm's tumor). Nephrotic syndrome is
      resistant to therapy. Renal failure develops in early childhood. Therapy is aimed
      to prevent oedema, denutrition, infections and thrombosis. Proteinuria does not
      recur after renal transplantation. Other causes are less frequent.

PMID- 16895670
TI  - [Clinical protocol. Pravastatin for the prevention of the destruction of the
      nutritional status of hemodialysis patients exhibiting chronic inflammation].

PMID- 16895671
TI  - [Slowing down the progression of chronic renal failure].

PMID- 16895672
TI  - [From Alport syndrome to benign familial hematuria: clinical and genetic aspect].
AB  - Alport syndrome (AS) is a hereditary glomerulonephritis variably associated with
      neural hearing loss and ocular abnormalities. The prevalence of the disease is
      estimated at approximately 1 in 50,000 live births. AS arises from mutations in
      genes encoding alpha chains constituting type IV collagen. In 85% of patients,
      the disease results from mutations in the COL4A5 gene located on X chromosome. In
      the hemizygous male, persistent microhematuria is present from early life, then
      proteinuria and renal insufficiency occur with time, leading to end-stage renal
      failure before age 40. In the heterozygous female, clinical manifestations vary
      from completely healthy state to end-stage renal failure, most often reached
      after the age of 40. In 15% of patients, the disease results from mutations in
      either the COL4A3 or the COL4A4 gene, both located on chromosome 2. When both
      alleles are mutated (autosomal recessive form), the phenotype is constantly
      severe, resembling that of the hemizygous male in the X-linked form. In the
      heterozygous individual, the clinical spectrum vary from the absence of any
      manifestation to the development of proteinuria - the so-called autosomal
      dominant AS -, and even renal insufficiency, sometimes reaching end-stage (after
      the age of 40) through the most frequently encountered phenotype, i.e. a
      persistently isolated microhematuria, accounting for the so-called benign
      familial hematuria (or healthy carrier state). The determinants of the phenotype
      remain largely unknown, so that it may be risky to predict renal prognosis in the
      individual with a single COL4A3/A4 mutation and an isolated microhematuria at the
      time of examination.

PMID- 16895673
TI  - [Anticancer drug-induced nephrotoxicity].
AB  - Nephrotoxicity is an inherent adverse effect of certain anticancer drugs. Anti
      neoplasic drugs have a narrow therapeutic index and the amount of drug necessary
      to produce a significant reduction in tumour burden usually produces significant
      nephrotoxicity. The dosage used in clinical trials represents often the maximum
      tolerated doses determined during phase I drug evaluation. Greater toxicity is
      acceptable during curative therapy than during palliative therapy. But cancer
      patients often exhibit excretory reduced organ function. Modulation of
      pharmacokinetics and pharmacodynamics of these drugs in cancer patients is
      therefore necessary in order to improve tolerance. Patients with malignancies are
      particularly vulnerable to development of renal abnormalities. Conversely,
      patients with renal abnormalities who have undergone kidney transplantation are
      at high risk for malignancy. Clinical syndromes of renal involvement are diverse
      and sometimes insidious. Despite the recent advances in understanding the
      mechanism of anticancer drug nephrotoxicity, prevention still relies on drug
      dosage decrease and active screening for renal abnormalities as part of the usual
      biological work up in patients treated with anticancer drugs.

PMID- 16895674
TI  - [Effects of tacrolimus vs cyclosporin-A on bone metabolism after kidney
      transplantation: a cross-sectional study in 28 patients].
AB  - BACKGROUND: Controversy exists about the effects of calcineurin inhibitors on
      bone metabolism. We decided to compare the effects of CyA vs FK506 on bone
      metabolism of kidney recipients. PATIENTS AND METHODS: From 94 patients grafted
      at the University Hospital of Nice between 1996 and 1999 treated either by CyA
      (N=49) or by FK506 (N=45), we selected 14 pairs (18 M, 10F), matched for gender,
      BMI, time lapsed since transplantation and gonadal status in females. Patients
      with>1 transplantation or>1 rejection episode were excluded. Cumulative dose of
      steroids was recorded. Bone mineral density (BMD) was mesured at heel and
      forearm, as well as serum concentration of calcium, phosphate, parathyroid
      hormone (PTH), vitamin D metabolites, C-telopeptide (CTX), creatinine, estradiol
      as well as Bone Alkaline Phosphatase (BAP) activity. RESULTS: Despite the
      matching, time on hemodialysis was longer in FK506 group. Cumulative dose of
      steroids was similar between groups. There was no difference between groups in
      BMD and biochemical parameters except for estradiol serum levels which were
      dramatically lower in FK506 than in CsA (P=0,02) and for a trend (p=0,08) for BAP
      and CTX to be higher in FK506 than in CsA. CONCLUSIONS: BMD is not lower in FK506
      than in CsA-treated patients although exposure to hyperparathyroidism was longer
      and estradiol levels were lower in the FK506 than in the CsA group. These data
      suggest that FK506 may have a favorable bone effect to compensate for these
      deleterious factors. This hypothesis remains to be tested in longitudinal
      studies.

PMID- 16895675
TI  - [Influence of hemodialysis on total and free malondialdehyde measured by a new
      HPLC method].
AB  - Accurate evaluation of oxidative stress is needed for patients on chronic
      hemodialysis (HD), as cardiovascular risk level seems related to it. Oxidative
      stress is often evaluated by measuring an end product of lipoperoxidation named
      malondialdehyde (MDA). However, the most common technique for measuring MDA, the
      Thio Barbituric Acid Reactive Substances method (TBARS), is known to be sensitive
      but poorly specific. We measured true total and free plasma MDA in fifty-four
      unselected patients on long-term HD, before and after HD sessions, by a new,
      highly specific HPLC method. Total and free MDA were higher before than after
      dialysis. Essentially, free MDA was decreased by HD but its fractional decrease
      was lower than that of urea or creatinine. This confirms that, in fact, free MDA
      is more or less bound to low molecular weight compounds and/or suggests that MDA
      may be produced mainly during HD sessions. We propose this new tool to further
      explore the relationship between oxidative stress, HD and true MDA.

PMID- 16895676
TI  - [Water used for hemodialysis equipment: where is Pseudomonas aeruginosa?].
AB  - The water used in dilution of the dialysis solutions constitutes an essential
      element of the efficiency and the safety of this therapeutics. Water must be
      specifically treated, and some technical rules must be respected, such as
      disinfection of the equipment for water treatment, to guarantee a satisfying
      level for whole the installation. This article reports the investigations, which
      were led to find the spring of Pseudomonas aeruginosa which contamined in a
      recurring way the water feeding dialysis equipment. The observation of
      samples'chronology and an analysis of the sanitary pad suggested a contamination
      during disinfection. Sample of residual water from the pump used for the
      injection of Dialox identified this reservoir as origin of the contamination. To
      stop this contamination by P. aeruginosa, a pump maintenance revision and purges
      of the system were used.

PMID- 16895677
TI  - [Antopol-Goldman lesion: a rare cause of hematuria].
AB  - An Antopol-Goldman lesion or subepithelial pelvic hematoma of the kidney is a
      rare cause of hematuria. We described a 26 year-old man hospitalized for
      macroscopic hematuria associated with a subepithelial hematoma whose development
      might have been favored by arterial hypertension secondary to a renal artery
      stenosis.

PMID- 16895679
TI  - [Shared protocols and patient information guides in pediatric nephrology].

PMID- 16895678
TI  - [Nephroprotection: how to slow the progression of chronic renal insufficiency?].
AB  - Most nephropathies are characterized by a progression that may result in end
      stage renal failure (ESRF). Apart from the specific treatment implemented when
      possible, ESRF may be delayed by nephroprotective therapy. Following the
      definition of the risk factors likely to induce progressive renal disease, the
      various therapeutic strategies that may play a nephroprotective role are
      reviewed. The potential results are described with regard to published data, in
      particular randomised trials, as recommended by the evidence-based medicine
      principles. Blockade of the renin-angiotensin system plays a major role in terms
      of nephroprotection. However, this strategy should not replace lifestyle measures
      and pharmacological treatment of the metabolic disorders associated to
      nephropathies.

PMID- 16895680
TI  - [Corticosensitive nephrotic syndrome (or nephrosis) in children. Therapeutic
      guideline proposed by the Pediatric Society of Nephrology].

PMID- 16895681
TI  - [Backward flow of blood in the extracorporal circuit pressure transducers of the
      generator-monitors of hemodialysis].
AB  - Transmission of hepatitis C virus between hemodialysis patients occurs mainly
      between the patients treated simultaneously in the same sector or in the same
      room. The other mode of viral transmission occurs between two patients treated
      successively with the same hemodialysis generator-monitor and sharing the same
      environment. One of the vectors of this last mode of transmission could be the
      contamination of the system of measurement of pressure of the extracorporal blood
      circuit. In July 2004, the French health products safety agency (Agence francaise
      de securite sanitaire des produits de sante, Afssaps) published a recommendation
      on these systems of measurement of pressure. i) The recommendation points out the
      optional preventive measures that users and manufacturers can carry out: (a) the
      manufacturers can propose tight systems of measurement of pressure, based on the
      deformation of a device; (b) the users can add a second protective filter on the
      external tubing connecting the blood circuit to the machine; (c) the
      manufacturers can add additional protective filters on the internal tubings of
      the machine. ii)The recommendation indicates the actions to be carried out
      obligatorily in the event of backward flow of blood in the last external
      protective filter: the soiled filter must be replaced and the causes of the
      backward flow must be analyzed and corrected; after the session, the monitor must
      be taken out of the unit and checked by a technician. The technician must replace
      all the elements located downstream from a soiled protective filter: tubings,
      drip chamber level control system, and pressure transducer. When these elements
      are protected by internal filters, only tubings and the first internal filter not
      soiled must be replaced. Precautions with regard to the systems of measurement of
      pressure must supplement standard precautions of hygiene essential in
      hemodialysis units.

PMID- 16895682
TI  - [The role of neutrophils during allograft rejection].
AB  - Because rejection of allografts is primarily caused by T and B lymphocyte
      responses to allogeneic histocompatibility molecules, the role of innate immunity
      in organ transplant rejection is often overlooked. However, the very first
      damages to vascularized organ allografts are caused by ischemia-reperfusion, an
      inflammatory reaction involving activation of vascular endothelial cells and
      release of neutrophil chemoattractants. Herein, we review experimental
      observations suggesting that the early neutrophil influx in organ transplants
      favors T cell-mediated rejection.

PMID- 16895683
TI  - [Occupational exposure to blood and body fluids in haemodialysis health care
      workers: epidemiological data and prevention in France].
AB  - Health care workers (HCW) in haemodialysis units are confronted with a
      significant risk of occupational exposure to blood and body fluids. The
      prevalence of bloodborne viruses is high among haemodialysis patients. The data
      presented here relates to the extraction of 121 occupational exposures notified
      to occupational health departments by haemodialysis HCW, documented between
      January 1995 and December 1999 in a network of 54 volunteer hospitals in Northern
      France. The exposures notified in haemodialysis wards were needlestick injuries
      in 85 cases (70.2%), splashes to the eyes or non-intact skin in 30 cases (24.8%)
      and cuts in 6 cases (5.0%). Connection and disconnection of dialysis catheters to
      fistulae, blood sampling procedures and injections alone were involved in
      approximately 3 notified exposures out of 4 (46.3, 14.9 and 11.6% respectively
      for a total of 72.8%). The principal mechanisms for exposure were the handling of
      blood-soiled needles and instruments or involved the handling of sharps
      containers. Haemodialysis fistula needles were involved in only 12 (13.2%) of
      notified percutaneous injuries. Nearly 2/3 (63%) of 91 notified percutaneous
      injuries could have been avoided by the observance of universal/standard
      precautions alone and the use of safety devices which were available at the time.
      The collection and analysis of occupational exposures can serve as basis for an
      assessment of practices, devices and safety equipment to increase HCW safety in
      haemodialysis wards.

PMID- 16895684
TI  - [Hepatorenal syndrome in patients with liver cirrhosis].
AB  - Hepatorenal syndrome is a particular form of functional renal failure which may
      develop in patients with liver cirrhosis. On a clinical standpoint, precise
      diagnostic criteria have been established to clearly define this entity, whereas
      recent advances in the understanding of the biology of vasoactive mediators and
      the physiology of microcirculation have allowed to better anticipate its
      pathophysiological mechanisms. During the course of cirrhosis, sinusoidal portal
      hypertension leads to splanchnic and systemic vasodilation, responsible for a
      reduction of effective arterial blood volume. As a result, a state of intense
      renal vasoconstriction develops, leading to renal failure in the absence of any
      organic renal disease. At this stage, liver transplantation is the only
      definitive therapy able to reverse renal dysfunction. In recent years, innovative
      therapies have shown promise to prolong survival in patients with hepatorenal
      syndrome, including the administration of analogs of vasopressin (mainly
      terlipressin), the insertion of transjugular intrahepatic portosystemic shunts
      and the use of novel techniques of dialysis. On a preventive viewpoint, several
      simple measures have been shown to reduce the risk of hepatorenal syndrome in
      cirrhotic patients, including the appropriate use of diuretics, the avoidance of
      nephrotoxic drugs, the prophylaxis of spontaneous bacterial peritonitis and
      optimal fluid management in patients undergoing large volume paracentesis.

PMID- 16895685
TI  - [Atherosclerosis and the kidney].
AB  - Diffuse atherosclerosis entails a 15-30% risk of plaques on renal arteries
      (ARAS), with a correlation with coronary atherosclerosis. Ischemia induces
      generation of angiotensin II (Ang II) that maintains sufficient hydrostatic
      pressure within the tuft to preserve the GFR. Ang II inhibition suppresses this
      protective mechanism. In fact, any antihypertensive drug may lead to reaching a
      "critical perfusion pressure". ARAS should be suspected in case of renal
      asymmetry. It should also be envisaged in case of "flash pulmonary edemas".
      Ultrasonography and renal tomography show aortic calcifications and often the
      outline of an abdominal aortic aneurysm. Tomodensitometry may detect large aorto
      renal plaques. Spiral scanner tomography represents a progress, in terms of renal
      artery imaging and of renal cortical atrophy. Magnetic resonance imaging is less
      accurate but avoids iodine toxicity. The best noninvasive method is pulsed echo
      doppler. It is particularly useful for evaluating stenoses progression. Some
      stenoses progress to renal atrophy and renal artery thrombosis, whereas others
      follow a stable course. Pulsed Doppler helps predict whether revascularization
      will improve renal function, according to the resistance index. Renal
      arteriography entails a high risk of cholesterol crystal embolism. However, it is
      the obligatory first step for angioplasty and stent positioning, indicated when
      the kidney is not atrophic. The indication for revascularization essentially
      depends on evaluation of the benefits vs risks of angioplasty or surgery. Some
      publications underscore the frequent stability of renal function and the fact
      that, revascularized or not, most patients will shortly die of myocardial
      infarction. Renal cholesterol crystal embolism (CCE) is a severe condition, which
      occurs when large arteries undergo surgery, aortography or interventional
      radiology. Anticoagulants are a frequent cause of CCE. CCE may also occur
      spontaneously, resulting in slowly progressive renal insufficiency. Migration of
      crystals in small caliber intrarenal arteries induces obstruction, followed by an
      inflammatory reaction. The clinical picture resembles angiitis, with laboratory
      evidence of inflammation along with high eosinophil counts and
      hypocomplementemia. Diagnosis rests on: 1) a iatrogenic event in a patient with
      an atherosclerotic background; 2) examination of the skin disclosing purple toes,
      small necrotic lesions and livedo of the lower limbs. Crystals may also be found
      by funduscopy. Skin or muscle biopsy are contributive in showing crystals and
      help avoid renal biopsy; 3) other localizations involve the mesenteric
      circulation and the central nervous system. Until recently, the prognosis was
      considered disastrous. However, a recently published treatment schedule proved
      efficient in reducing mortality. A last issue regarding the relationships between
      atherosclerosis and the kidney deserves mention. In an autopsy-based study it was
      shown that atherosclerosis per se is accompanied by an increase in the glomerular
      surface area along with a greater proportion of obsolescent glomeruli by
      comparison with matched controls. Finally, it should be recalled that atherogenic
      hyperlipidemia usually aggravates the course of any renal disease, including
      ARAS. Treatment with statins is indicated in all forms of atherosclerotic renal
      disease.

PMID- 16895687
TI  - [Choosing between peritoneal dialysis and haemodialysis: a critical appraisal of
      the literature].
AB  - In France, incidence and prevalence of end-stage renal disease (ESRD) are
      increasing, requiring a more rational use of available replacement therapies. To
      help practitioners make their choice between treatment modalities of peritoneal
      dialysis (PD) and haemodialysis (HD), critical appraisal of relevant literature
      has been conducted. Although few absolute or relative contraindications for PD
      and HD exist, arguments in favour of one versus the other dialysis technique can
      be made. When patients receive adequate and complete information, their
      preference is neutral between PD and HD. To date, no trial presenting a
      convincing level of evidence has been published which demonstrates the
      superiority of one technique compared to the other. Relative to mortality, it
      appears that no difference can be observed between the two modalities. However,
      in those instances where patients expect a rapid transplantation, PD is the
      preferred technique. This analysis suggests that peritoneal dialysis and
      haemodialysis are not competitive but rather complementary treatments. It is
      therefore interesting to identify the reasons supporting the various choices
      between the two different treatment modalities amongst France's regions. Access
      to transplant, economic or organizational factors must be considered.

PMID- 16895689
TI  - [The adaptor protein Lnk modulates endothelial cell activation].
AB  - Lnk is an adaptator protein involved in B lymphocytes and platelet
      differentiation and in T lymphocyte activation. We previously reported on Lnk
      expression and regulation in endothelial cells (ECs) upon activation. In the
      present study, the involvement of Lnk in the tumor necrosis factor alpha
      (TNFalpha) pathway was investigated in vitro through Lnk overexpression in
      primary cultures of human endothelial cells. Using a recombinant adenovirus
      encoding human Lnk, we first demonstrated that Lnk overexpression does not induce
      vascular cell adhesion molecule-1 (VCAM-1) suggesting that Lnk does not promote
      ECs activation. However, Lnk overexpression significantly reduced TNFalpha
      mediated expression of VCAM-1 (at mRNA and protein levels) in activated EC as
      compared with controls. Western blot analysis showed that Lnk overexpression in
      HUVEC was associated with phosphorylation of Akt kinase (at Ser 473) with no
      effect on IkappaBalpha, the specific inhibitor of NFkappaB, indicating that Lnk
      promotes activation of the phosphatidylinositol 3-kinase (PI3-kinase) pathway in
      ECs. Altogether, these results suggest that, in ECs, Lnk may participate to a
      regulatory pathway involving the PI3-kinase and modulating the inflammatory
      response.

PMID- 16895688
TI  - [Fluvastatin affects HLA class I expression on endothelial cells].
AB  - Originally designed to target elevated lipids, the "traditional" cause of
      atherosclerosis, statins might also confer vascular benefit by directly or
      indirectly modulating both the inflammatory and immune responses. Statins have
      been shown to downregulate MHC class II and CD40 expression on activated
      endothelial cells (EC). In this study, we investigate the potential effect of
      statins on MHC class I expression and regulation in response to IFNgamma. Primary
      cultures of human ECs have been treated with increasing doses of fluvastatin
      (0.01; 0.1 and 1 microM) with or without IFNgamma for 48 hours. Surface
      expression of MHC class I and class II has been analyzed by flow cytometry. Our
      data indicate that fluvastatin increases MHC class I expression on quiescent ECs
      by a dose-dependent effect. Furthermore, fluvastatin potentiates the MHC class I
      upregulation but prevents MHC class II induction triggered by IFNgamma. These
      effects are reversed by mevalonate. In conclusion, our results suggest that while
      decreasing MHC class II expression, fluvastatin (at 0.1 and 1 microM) upregulates
      MHC class I expression on ECs. Functional consequences of statin-mediated
      modulation of MHC on ECs have still to be elucidated in vitro and in vivo.

PMID- 16895690
TI  - [Medical prescriptions in haemodialysis patients: critical analysis].
AB  - AIM: The aim of the study is to analyse haemodialysis patients' prescriptions
      accordance with legal registrations in 64 chronic haemodialysis patients during a
      one-month follow-up period. RESULTS: Patients are taking 9.6+/-3 different drugs.
      A mean of 2.4+/-1.3 prescriptions per patient disagree with the recommended drug
      use. The directions for use in this specific population are defective in 89%.
      Moreover, at least one drug-drug interaction is found in 78% of our patients.
      CONCLUSION: Only 8% of the studied hemodialysis patients benefit from
      prescriptions in agreement with the legal recordings, as a consequence of the
      lack of drug studies in this particular population. Therefore, clinicians have to
      rely on their own experience to establish their prescriptions, which can involve
      their responsibility in case of litigation. Furthermore, the frequency of drug
      drug interactions in these polymedicated patients implies that a close
      pharmaceutical follow-up should be implemented.

PMID- 16895691
TI  - [Tumorlike muscular sarcoidosis with hypercalcemia and acute renal failure].
AB  - At the end of assessment of an hypercalcemia with acute renal failure in a
      seventy year-old man, is discovered a tumorlike muscular sarcoidosis of both
      thighs whose steroid treatment quickly proves effective. Rarity of such forms
      urges us to report this observation which allows to remind that, in case of a
      suggestive picture of sarcoidosis, it is necessary to look minutely for any
      muscular abnormality.

PMID- 16895692
TI  - [Emphysematous pyelonephritis. Two cases].
AB  - The emphysematous pyelonephritis is a rare and severe renal infection
      characterized by the presence of gas in renal parenchyma and its perirenal
      spaces. We report two cases of emphysematous pyelonephritis in two diabetic women
      (53 and 50 years old respectively). In the first case, the treatment was based on
      nephrectomy because of the presence of a septic shock and three risk factors,
      which are acute renal failure, hematuria and thrombopenia. In the second case,
      the treatment was only medical. The evolution was favorable in the two cases. We
      insist in this article that this diagnosis should be considered in every female
      diabetic patient having severe acute pyelonephritis resistant to a well-conducted
      medical treatment.

PMID- 16895694
TI  - [Linking of blood urea and renal diseases].

PMID- 16895693
TI  - [Peritoneal dialysis].

PMID- 16895695
TI  - [Evolution of viral infection epidemiology in haemodialysis patients].

PMID- 16895696
TI  - [Prevalence of hepatitis C, hepatitis B and HIV infection among haemodialysis
      patients in Ibn-Rochd university hospital, Casablanca].
AB  - The viral infections are frequent in haemodialysis patients, notably those due to
      the hepatitis C virus (HCV), the hepatitis B virus (HBV) and the human
      immunodeficiency virus (HIV). The objective of this study is to determine the
      prevalence of the hepatitis C, the hepatitis B, the HIV infection in
      haemodialysis patients and the main risk factors for hepatitis C in the chronic
      haemodialysis patients treated in haemodialysis unit of Ibn Rochd University
      Hospital in Casablanca. This retrospective study was performed in 186 chronic
      haemodialysis patients and showed a high prevalence of HVC infection (76%), the
      prevalence of HBV infection was at 2%, none of the patients had detectable
      antibodies of HIV. Among the patients infected by the HCV, the mean duration of
      dialysis was 8,7 years. The mean number of blood units transfused was 16,5.
      Seventeen patients (11%) had no history of blood transfusion. In conclusion, the
      blood transfusion is not considered to be a like a major risk factor of the HCV
      infection in haemodialysis patients and this since the systematic detection of
      the anti-HCV antibodies in the blood donors. The nosocomial transmission of HCV
      seems to be the main risk factor HCV infection in the haemodialysis units
      requiring a strict adherence to infection control procedures for prevention of
      HVC infection in haemodialysis patients.

PMID- 16895697
TI  - [Drug-induced nephrotoxicity: bibliography from January 2003 to December 2004].
AB  - Drug-induced kidney injury is a major side effect in clinical practice. Renal
      injury associated with drugs may involve several components of the kidney:
      glomerulus, tubules, interstitium and blood vessels. Acute renal failure may
      occur as a major reaction to many drugs. Moreover, therapeutic agents may induce
      an allergic reaction leading to interstitial inflammation and tubular damage. In
      this article, we present an updated version of the bibliography containing the
      case reports of nephrotoxicity published in the international literature from
      January 2003 to December 2004.

PMID- 16895698
TI  - [Tubular transporters OAT1 and MRP2 and clearance of adefovir].
AB  - Adefovir is transported by the organic anion transporter (OAT1) and the multidrug
      resistant protein (MRP2, 4 and 5). We studied adefovir clearance in rat after
      inhibition of transporters by probenecid and in TR- rats, in which MRP2 is
      lacking. After treatment by probenecid or placebo, pharmacokinetics of adefovir
      10 mg/kg was studied via population modeling (NONMEM). The fraction of drug
      excreted in the urine was low. Renal clearance of adefovir was significantly
      lower (P < 0.05) in probenecid TR- rats (0.03 +/- 0.02 l/hour) than in normal
      control (0.09 +/- 0.05 l/hour), in normal probenecid (0.10 +/- 0.07 l/hour) and
      in TR- control rats (0.13 +/- 0.07 l/hour). In vivo in rats MRP2 mutation alone
      did not affect adefovir clearance suggesting that MRP2 does not play a critical
      role in the secretion of adefovir. Additional pharmacological inhibition of
      transporters decreased renal clearance, which may reflect inhibition of
      compensating transport mechanisms activated when MRP2 is lacking.

PMID- 16895699
TI  - [Nephrolithiasis-induced ESRD: frequency, causes and prevention].
AB  - Nephrolithiasis still remains a too frequent - and under-appreciated - cause of
      end-stage renal disease (ESRD), and this is all the most unfortunate since such
      an untoward course is now preventable in most cases. Among 1391 patients who
      started maintenance dialysis at Necker hospital between 1989 and 2000,
      nephrolithiasis was identified as the cause of ESRD in 45 of them, an overall
      prevalence of 3.2%. Infection stones accounted for 42.2% of cases, calcium stones
      for 26.7%, uric acid stones for 17.8% and hereditary diseases for 13.3%. The
      proportion of nephrolithiasis-associated ESRD declined from 4.7% to 2.2% from the
      1989-1991 to the 1998-2000 period, as a result of the decreased incidence of ESRD
      in patients with infection and calcium nephrolithiasis. Based on our observations
      and on published reports, it emerges that most cases of nephrolithiasis
      associated ESRD were due to sub-optimal management (especially in the case of
      infection or cystine stones) or to late (or erroneous) etiologic diagnosis,
      precluding early institution of appropriate therapeutic measures. In particular,
      several patients with primary hyperoxaluria or 2,8-dihydroxyadeninuria were
      diagnosed while already on dialysis or after unsuccessful kidney transplantation,
      due to wrong initial diagnosis. In conclusion, thanks to recent advances in
      diagnosis and management of stone formers, ESRD should now be prevented in the
      great majority of patients, at the condition of early etiologic diagnosis based
      on accurate morphoconstitutional analysis of calculi and metabolic evaluation,
      and early implementation of appropriate preventive medical treatment.

PMID- 16895700
TI  - [Primary peritonitis in children with nephrotic syndrome].
AB  - The primitive peritonitis (PP) is one of the rare but severe complications of the
      nephrotic syndrome. Through a series of 25 children who suffer from a primitive
      peritonitis complicating or revealing a nephritic syndrome, we tried to analyse
      the epidemiological and bacteriological aspects of these peritonitis. The mean
      age of the children is 7 years old with neat male predominance (3 boys/1 girl).
      Two patients presented 2 episodes of PP. In 16% of the cases, the PP revealed a
      nephrotic syndrome. The isolated germs in our series are the Escherichia coli
      (45.5%) and the pneumococcus (36.5%), in 56% of the cases, the germ has not been
      identified. The precocious large use of probabilist antibiotherapy permitted a
      favourable evolution with nil rate of mortality.

PMID- 16895701
TI  - [Molecular mechanisms involved in kidney ischemia-reperfusion].
AB  - Acute renal failure (ARF) is still associated with high mortality. It is the
      consequence of a set of phenomena leading to a low glomerular filtration rate
      resulting, at least partly, from a misregulation of renal blood flow resulting
      itself from injuries at the epithelial and endothelial level. The outer medulla
      seems to be the region of the kidney the most affected by ischemia. Investigation
      at the histological level reveals a partial destruction of the renal epithelium
      generated by necrosis and/or apoptosis, loss of cell polarity, cell desquamation
      into the lumen and endothelial cell swelling. The recent advances in the
      comprehension of this pathology underline the major role of inflammation, which
      is probably responsible for the worsening and the persistence of ARF. Studies at
      the molecular level have pinpointed the implication of many signalling pathways
      such as apoptosis, G-protein signalling, various receptor and kinase activation.
      The characterisation of the molecular events involved in ARF should help in our
      approaches to prevent and treat ARF. The understanding of the adaptation
      mechanisms to ischemic stress (conditioning) is probably one of the most
      promising research area of this field in terms of medical applications.

PMID- 16895702
TI  - [Boredom once arose from uniformity].

PMID- 16895703
TI  - [Delayed graft function: a frequent but still unsolved problem in renal
      transplantation].
AB  - Delayed graft function (DGF) is a frequent and well-known complication of renal
      transplantation, which occurs in 30% of cadaver kidney allografts. It has an
      economic cost that is the result of prolonged patient hospitalization and the
      need for hemodialysis sessions; it also increases the risk of acute allograft
      rejection and may affect long-term graft survival. Lots of risk factors were
      identified, like donor hemodynamic compromise or prolonged cold ischemia time;
      however, incidence of DGF remains high due to the frequent use of marginal donors
      due to organ shortage. Recent advances in the pathophysiology of DGF point the
      importance of the ischemia-reperfusion injury mechanisms and some therapeutics
      that may reduce them are under investigation, like the use of new solutions to
      improve organ preservation and the use of some antioxidant and anti-inflammatory
      drugs.

PMID- 16895704
TI  - [Regional disparities in the management of dialysed patients in France in 2003].
AB  - Epidemiologic data on end-stage renal disease (ESRD) treated with renal dialysis
      remain sparse and incomplete in France because there is no national registry of
      dialysis patients. The aim of this study was to determine the characteristics
      (age, gender, comorbidities, associated handicap) of patients treated with renal
      dialysis and to compare the dialysis regional practices. We performed a cross
      sectional descriptive study from June 2 to June 8, 2003 in all renal dialysis
      units by enrolling all the patients residing in France with ESRD who were
      dialysed during that week, irrespective of the treatment they received or where
      they were being treated. In 2003, the type of dialysis units available and the
      technique they employ were quite different from one region to another, varying
      from 41.1 to 70.2% for highly specialized unit, 9.4 to 48.4% for self-care
      hemodialysis, and 2.9 to 26.5% for peritoneal dialysis.

PMID- 16895705
TI  - [The evolution of the hypervariable region-1 of hepatitis C virus may predict
      liver fibrosis outcome after renal transplantation].
AB  - The aim of our study was to assess hepatitis C virus (HCV) evolution and long
      term liver histology outcome in anti-HCV(+)/RNA(+) renal-transplant (RT)
      patients. Fifty-five anti-HCV(+)/RNA(+) RT patients underwent every 3-4 years
      after transplantation liver biopsies (LB) (2 LBs, N = 55; 3 LBs, N = 44; 4 LBs, N
      = 10). The hypervariable region (HVR)-1 of the HCV genome from all patients was
      characterized over time. Overall, the rate of liver fibrosis progression was 0.07
      +/- 0.03 Metavir units/year. We identified three groups of patients: those in
      whom liver fibrosis remained stable (group I, N = 21), those with progressing
      liver fibrosis (group II, N = 21), and those with a regression in liver fibrosis
      (group III, N = 13). Initial fibrosis stage and high diversification of the HVR-1
      of HCV genome between the transplantation and the first liver biopsy were
      independent factors associated with liver fibrosis regression. In conclusion, in
      this study, after renal transplantation, HCV infection is not harmful upon liver
      histology in more than fifty percent of the patients. The diversification of the
      HVR-1 of the HCV genome might be used to predict liver fibrosis outcome.

PMID- 16895706
TI  - [Glomerulonephritis with organized immunoglobulin deposits].
AB  - Glomerulonephritis with organized immunoglobulin deposits are heterogeneous and
      may be encountered in a variety of renal disorders. It is particularly important
      to determine the exact types of immunoglobulin deposited and their
      monotypy/monoclonality, using specific anti-light chain conjugates and in some
      instances, anti-heavy chain subclass conjugates. The histologic pattern and
      identification of monotypic Ig deposits in renal tissue are in some cases
      sufficient for the diagnosis of AL amyloidosis, type I cryoglobulinic
      glomerulonephritis or "Randall-type" monoclonal immunoglobulin deposition disease
      (MIDD). Electron microscopy is particularly valuable for the precise localization
      of Ig deposits and for determing the pattern of deposition: organized,
      homogeneous (non-organized or granular) or mixed. New entities in the broad
      spectrum of Ig deposition diseases are emerging from electron microscopy studies
      of renal diseases. We propose here a comprehensive classification for diseases
      featuring the organized deposition in tissues of Ig.

PMID- 16895707
TI  - [Treatment of anemia caused by chronic kidney failure in adults].

PMID- 16895708
TI  - [Should we still publish in French?].

PMID- 16895709
TI  - Lessons learnt from the 4D trial.
AB  - Renal dysfunction alters the pathogenesis of cardiovascular disease (CVD)
      profoundly conferring a very high-risk to the patients. Currently strategies are
      developed to combat CVD and clinical studies test a number of hypothesis. In this
      setting the results of the 4D study, comparing atorvastatin with placebo on
      cardiovascular outcomes in 1255 type 2 diabetic patients on maintenance
      hemodialysis, came as a great and unsuspected surprise. After a median follow-up
      of 4 years atorvastatin (20 mg/d) decreased the relative risk by 8% (95%
      confidence interval, 0.77-1.10; P=0.37) despite a high number of cardiovascular
      events and an overall 24% cardiovascular mortality. This indicates, that the risk
      in type 2 diabetic patients on hemodialysis origins from factors other than an
      atherogenic lipoprotein phenotype alone. Due to non-significant effects of
      atorvastatin on the primary endpoint and the different quality of such endpoints
      in dialysis patients as well as an unexplained higher rate of fatal strokes in
      atorvastatin treated patients we do not recommend to initiate statin treatment in
      patients with type 2 diabetes mellitus undergoing hemodialysis therapy at the
      present time. Statin therapy should be implemented earlier during the course of
      progressive vascular damage.

PMID- 16895710
TI  - [Renal transplantation in the elderly: a survey].
AB  - For ten years, an increase in the number of elderly patients on renal transplant
      waiting lists has occured. In an attempt to close the widening gap between supply
      and demand and because the demand for kidneys for younger patients already
      surpasses the supply, transplant physicians nowadays accept organs from older
      donors that might have been deemed inappropriate in the past. Programs of age
      matching between donors and recipients and of dual-kidneys transplantation have
      emerged. The initial results of these programs are encouraging with excellent
      patient and graft survival at one and three years.

PMID- 16895711
TI  - [Patterns of nephrology referral and predialysis management of patients with
      chronic kidney disease].
AB  - INTRODUCTION: Numerous studies showed that late referral (LR) to a nephrologist
      of patients with chronic kidney disease stated by a simple quantitative criterium
      (initiation of renal replacement therapy (RRT) within 3 or 4 months of referral
      to a nephrologist, independantly from the quality of care) is associated with
      worse survival rate, limited to the first 3 months following the initiation of
      RRT. We wanted to test a criterium of LR definition supposing a more important
      "dose of nephrological care", to try to understand the reasons of this early
      death. METHODS: One hundred and thirty-eight patients receiving their first RRT
      in 1999 and 2000 in Valenciennes (France) were enrolled in this study. Two LR
      definitions were used: a qualitative criterium C1 (whether the patient was under
      an uninterrumpted nephrological pre-dialysis care - independantly from the date
      of the nephrological referral - or not) and a more simple quantitative criterium
      C2 (initiation of RRT within 3 months of referral to a nephrologist). Comorbidity
      was assessed by Charlson's score. The analysis concerned the respective influence
      of C1 and C2 on the clinical and biological effects of chronical azotemia, on the
      circumstances at first RRT (emergency first dialysis, pulmonary edema, type of
      vascular access), and on survival rates (Kaplan-Meier's analysis). RESULTS: LR
      rates are 23% according to C1 and 20% according to C2. Comorbidity is similar in
      the different groups. Whatever the definition criterium, LR is associated to a
      lower hemoglobin and albumin, a more severe acidosis, a longer duration of first
      hospitalization, and higher rate of emergency first dialysis and use of central
      temporary catheter. The survival rates at 2 years following the first RRT of
      lately referred patients are 53% according to C1 (vs 86% for early referred
      patients, P<0,001) and 56% according to C2 (vs 84%, P<0,05). For both, early
      death (within the first 3 months) explained the observed differences of survival
      rates. CONCLUSION: In this study, early death of lately referred patients seems
      to be independant from the criterium of definition of LR. Elements of explanation
      are suggested, and can lead to further prospective studies.

PMID- 16895712
TI  - [Withdrawal from dialysis: a frequent but sometimes difficult situation].
AB  - Withdrawal from dialysis is a frequent cause of death in chronic dialysis
      patients in a French population, as it is in North America. In both populations
      dialysis was withdrawn in about 20%, but the characteristics of patients and the
      decision-making procedure were different. In France, patients in whom dialysis
      was withdrawn were most often at the end of their life, and the physician
      essentially made the decision. This decision was often difficult to make and be
      accepted, particularly when the patient chose himself to stop the dialysis, even
      if life expectancy would be long on dialysis. A discussion including the patient,
      his family and the medical staff is crucial. The modification of the French law
      about the rights of patients at the end of their life will be assistance when
      such decisions take place, especially in non-conscious patients who are at the
      end of their life, and in those who want to stop dialysis. Philosophical and
      ethical reflection with its concepts for autonomy and dignity can be a valuable
      aid in such situations.

PMID- 16895713
TI  - [Patient information: the dialysis].

PMID- 16895714
TI  - [Proteinuria].
AB  - Several health organizations recommend that people be regularly checked for
      proteinuria to detect and treat kidney disease before it progresses. Proteinuria
      detected by a simple dipstick test should be confirmed by a quantitative
      measurement to assess persistent proteinuria. Most proteins are too big to pass
      through the kidneys' filters into the urine unless the kidneys are damaged.
      Markers of kidney damage in addition to proteinuria include abnormalities in the
      urine sediment, ultrasound of the kidneys and estimation of kidney function
      (creatinemia to calculate glomerular filtration rate). These assessments provide
      clues to the type (diagnosis) of chronic kidney disease and will the risk for
      developing progressive kidney failure. Thus, early detection of kidney disease
      will result in a more timely introduction of therapy that may slow the course of
      kidney disease. Microalbuminuria (albumin excretion above the normal range) that
      a marker of microvascular lesions in diabetes and hypertension is associated with
      a worth cardiovascular prognosis. Level of proteinuria in excess of 3,0 g/d in
      glomerular disease strongly determines the extent of kidney damage and renal
      prognosis.

PMID- 16895715
TI  - [Metastatic renal failure].
AB  - A 52-year-old man, treated 15 months earlier for a poorly differentiated
      bronchial adenosquamous carcinoma, was admitted for oligoanuric renal failure
      preceded by macroscopic hematuria. Clinical and paraclinical investigations were
      unremarkable except ++proteinuria and mild echographic enlargement of both
      kidneys. Bilateral renal biopsy disclosed replacement of normal renal tissue by
      an adenocarcinomatous proliferation. Despite transient improvement and cessation
      of hemodialysis, the patient died one month later. Analysis of literature reveals
      that secondary kidney tumours -especially of bronchial origin- are more frequent
      than primary ones, but that cases of renal failure are uncommonly reported,
      probably because of underdiagnosis, poor prognosis and limited therapeutic
      issues. Features of previously published cases are listed in a synthetic table.

PMID- 16895717
TI  - [What do large clinical trials learn us about cardiovascular and renal prevention
      in patients with type 2 diabetes mellitus and hypertension?].
AB  - Type 2 diabetes mellitus and hypertension are frequently associated.
      Cardiovascular morbidity is a major burden in these patients. Furthermore a renal
      disease appears in 40% of them that may lead to chronic terminal renal failure.
      Whatever the stage of the renal disease, it increases the cardiovascular risk. A
      majority of type 2 diabetic patients will eventually died of cardiovascular
      complications before having reached chronic terminal renal failure. Many large
      clinical trials including type 2 diabetic patients with hypertension have been
      performed in the last 20 years with cardiovascular morbidity and mortality as
      primary outcomes. These trials mainly evaluated the role of glycemic control, of
      hypertension as well as the decrease of LDL-cholesterol. Based on these trials,
      the prescription type of hypertensive type 2 diabetic patient should include,
      besides hygienic and dietary advices, antidiabetic treatment, thiazide and/or
      betablocker and platelet inhibitor. Statin should be prescribed for secondary
      prevention if serum LDL-cholesterol is above 1,3 g/l and for primary prevention
      depending on serum LDL-cholesterol and on the number of cardiovascular risk
      factors. The objectives are an HbA1c below 6,5%, a LDL-cholesterol below 1g/l and
      a blood pressure below 150/80 mmHg. The appearance of diabetic nephropathy alters
      the treatment and the therapeutic objectives. Many large trials aimed at
      preventing microalbuminuria (primary prevention), macroproteinuria (secondary
      prevention), and chronic renal failure (tertiary prevention) have been conducted.
      For primary prevention, angiotensin-converting-enzyme inhibitors should be
      prescribed in case of hypertension because they delay the appearance of
      microalbuminuria. For secondary prevention, angiotensin-converting-enzyme
      inhibitors and angiotensin-receptor blockers decrease albuminuria excretion rate
      and delay the appearance of macroproteinuria whatever the blood pressure.
      Tertiary prevention is based on angiotensin-receptor blockers since they slow
      down the decrease of renal function. The objectives are a blood pressure below
      130/80 mmHg and the regression or the reduction of albuminuria excretion rate.
      Intensified and target-driven interventions aimed at multiple risk factors
      implicated in cardiovascular and renal lesions, as successfully performed in the
      STENO-2 study, reduce the risk of cardiovascular and renal morbidity and
      mortality. In this article, large clinical trials having the prevention of
      cardiovascular and renal risks as primary outcomes were analyzed.

PMID- 16895718
TI  - [Differences in cardiac troponin I and T levels measured in asymptomatic
      hemodialysis patients with last generation immunoassays].
AB  - Previous studies reported cardiac troponin I (cTnI) and T (cTnT) levels to be
      higher than normal in a significant proportion of asymptomatic chronic
      hemodialysis (HD) patients without evidence of acute myocardial injury. We have
      therefore evaluated in such patients the accuracy of cTnI and cTnT determinations
      measured with last generation assays. Fifty chronic HD patients (34 males)
      without symptoms of acute myocardial ischemia were studied. Their mean age (+/
      SD) was 64.4+/-12.7 years, 22 patients (44%) had an history of cardiac ischemic
      disease and 19 (38%) were diabetics. Serum cardiac markers were measured with
      last generation assays before and after a single HD session and in a control
      group including 30 hospitalized patients without renal failure. The cTnI were
      determined with Dimension RxL "Improved method" assay (Dade Behring), the cTnT
      with Elecys "Third generation" assay (Roche Diagnostics) and the creatine kinase
      (CK) with Integra (Roche Diagnostics). The cTnI were also simultaneously
      determined with the assay previously used at our institution (Dimension RxL, Dade
      Behring), indicated as old-method-cTnI. With the last generation assay only 1
      patient (2%) had elevated cTnI (>0.1 microg/l) in the study group compared to
      none in the control group (P=NS). Instead, with the old-method-cTnI assay 11
      patients (22%) had elevated (>0.3 microg/l) predialysis cTnI levels (P<0.01
      compared to the "Improved method" assay). The predialysis cTnT levels were higher
      than normal (>0.1 microg/l) in 23 patients (46%), compared to none in the control
      group (P<0.01). The CK levels were elevated (>170 IU/L) in 4 dialysis patients
      (8%) compared to one (3,3%) in the control group (P=NS). The cTnT levels slightly
      but non-significantly diminished during dialysis (from 0.102+/-0.070 to 0.085+/
      0.067 mug/l, P=NS), while in the same time no changes were observed for cTnI and
      CK levels. In conclusion, the specificity of cTnI determinations in HD patients
      is greatly improved by the last generation assay (from 78 to 98%), and is
      actually similar to that observed in a population with normal renal function.
      Therefore cTnI, determined with the last generation assay used in the present
      study, can be reliably used for the diagnosis of acute coronary syndromes in HD
      patients. Instead, cTnT levels remain higher than normal in a significant
      proportion of asymptomatic HD patients (46%) and the reasons for this fact need
      further investigations.

PMID- 16895719
TI  - [Hospitalization of peritoneal dialysis patients: the impact of peritonitis
      episodes on the hospitalization rate].
AB  - Peritonitis is still a frequent complication in peritoneal dialysis patients.
      Medical guidelines have been established to manage this infection. These
      guidelines do not provide any information regarding the requirement for
      hospitalization. The main objective of this study was to evaluate the impact of
      peritonitis episode on the hospitalization rate and on the hospitalization
      duration in a centre where peritoneal dialysis patients were hospitalized in case
      of peritonitis. This was a retrospective study of incident peritoneal patients
      over a six years period. Among 101 peritoneal dialysis patients 65% were
      hospitalized. Two hundred and twenty hospital stays were registered. The total
      duration of hospital stays was 2091 days. The hospitalization rate was 2 per
      patient and per year, the hospital duration was 19 days per patient per year. Of
      the 220 hospital stays, 67 (30%) were due to a peritoneal infection. Peritonitis
      episodes represent 581/2091 (28%) days of hospitalization. The mean duration of
      hospitalization for peritonitis was 8.7+/-7 days. Among the patients hospitalized
      for a peritonitis episode, 57% were assisted by a nurse at home to perform their
      peritoneal dialysis exchanges. Of the 67 peritonitis episodes, 91% were
      discharged from the hospital without any complication. This study emphases the
      fact that peritonitis has an important impact on the hospitalization rate and on
      the hospitalization duration in peritoneal dialysis patients. In an attempt to
      decrease the rate of hospitalization, educational programs are clearly needed in
      order to treat more peritonitis without any hospitalization requirement.

PMID- 16895720
TI  - [Fungal sinusitis from endodontic origin. Some reflexions about an observation by
      an hemodialyzed patient].
AB  - About an observation of aspergillus sinusitis in an hemodialyzed patient,
      correlation between chronic maxillary sinusitis, its aspergillus origin and
      previous dental treatments is emphasized. Eventual severe complications then
      evolved in immunocompromised patients justify having the knowledge of this
      possible pathology in hemodialyzed and transplanted patients.

PMID- 16895721
TI  - [Acute post-infectious glomerulonephritis].

PMID- 16895722
TI  - The equine periodontium as a continuously remodeling system: morphometrical
      analysis of cell proliferation.
AB  - OBJECTIVE: The hypsodont equine cheek tooth erupts continuously throughout life.
      Tooth eruption is inevitably associated with a remodeling of the periodontium.
      One major process of remodeling in the PDL is cell proliferation. The aim of this
      study was to detect cell proliferation at different sites of the equine PDL in
      order to examine the dynamics of the periodontal cell population. DESIGN:
      Specimens from nine warm-blood horses were taken-- containing the PDL interposed
      between the cementum and the alveolar bone--at three designated levels:
      subgingival, middle, and apical. Cell proliferation was detected
      immunohistochemically by use of anti-Ki-67 in combination with an elaborate
      morphometrical procedure using an image-analysis program. Three zones of the PDL
      were distinguished in each specimen: a zone next to the dental cementum, a
      central zone, and a zone next to the alveolar bone. The PDL was divided into
      three levels and three zones, resulting in nine defined regions of interest.
      RESULTS: The proliferation index was high at the apical level and in the zone
      next to the alveolar bone. The opposite was true of cell density, which was high
      at the subgingival level and in a zone next to the dental cementum. CONCLUSIONS:
      Evaluation and statistical analysis of the parameters proliferation index and
      cell density in distinct, biologically appropriate sites of the equine PDL
      suggest the presence of dynamic processes like cell migration by which the cells
      of the PDL move from an area next to the alveolar bone towards the dental
      cementum, and in an apico-occlusal direction. Furthermore, our study confirms the
      close relationship between cell proliferation, cell migration, and eruption.

PMID- 16895723
TI  - Subcellular dynamics of protein kinase A activity visualized by FRET-based
      reporters.
AB  - cAMP-dependent protein kinase (PKA) mediates key cellular processes via
      compartmentalized activity, and the ability to track its activity in living cells
      should help increase our understanding of this precise regulation. Here, through
      systematic testing of new fluorescent proteins, we developed a new FRET-based A
      kinase activity reporter (AKAR), AKAR3, with a dynamic range of 31-41%, twice
      that of predecessors. Visualization of PKA activity at plasma membrane,
      cytoplasm, nucleus, and mitochondria was achieved. Targeting AKAR3 to outer
      mitochondrial membrane revealed that basal PKA activity at mitochondria differs
      from that in the cytoplasm, indicating differential regulation of PKA activity at
      different subcellular locations.

PMID- 16895724
TI  - A tree-based decision rule for identifying profile groups of cases without
      predefined classes: application in diffuse large B-cell lymphomas.
AB  - In this paper, we examined the utility of a forward growing classification tree
      as a supplement to cluster analysis for deriving a decision rule for the
      identification of profile groups when the cases do not belong to predefined
      classes. The technique was applied for the identification of low and high
      proliferation profile groups of diffuse large B-cell lymphomas according to the
      immunohistochemical expression levels of proliferation proteins. In a forward
      growing classification tree method, the size of the tree is controlled by the
      improvement (threshold value) in the apparent misclassification rate after each
      split. The classes used in the tree were defined using k-means clustering. The
      decision rule consisted of the splitting points of the split variables used. The
      methodology was applied to the histology data from 79 cases of diffuse large B
      cell lymphomas. Ten classes of individual cases were derived from k-means
      clustering. Then, a classification tree with a threshold of 2% was used to derive
      the decision rule. Branches at the left side of the tree consisted of individuals
      with a low proliferation profile and branches at the right side of the tree
      consisted of cases with a high proliferation profile. The classification tree, as
      a supplement method, not only identified but also provided decision rules for
      identifying profile groups. Finally, it also allowed for exploration of the data
      structure.

PMID- 16895725
TI  - A computer model for the clearance of insoluble particles from the
      tracheobronchial tree of the human lung.
AB  - A multi-compartment model for the clearance of insoluble particles from the
      tracheobronchial tree of the human lung was created. As a significant innovation,
      the model considers specific mass transfer paths that may play an important role
      for slow bronchial clearance. These include the accumulation of particulate mass
      in the periciliary sol layer, an uptake of stored particles by airway
      macrophages, and the endocytosis of deposited mass by epithelial cells. Besides
      the gel layer representing fast mucociliary clearance, all cellular and
      extracellular units involved into the slow clearance process are described by
      respective compartments which are connected by specific transfer paths. The
      gastrointestinal tract (GIT), lymph nodes (LN), and blood capillaries are
      included into the model as final accumulation compartments, to which mass is
      transferred via the airway route and the transepithelial path. Besides a basic
      version of the model describing the whole tracheobronchial region by one set of
      compartments, also an advanced approach is introduced which, in accordance with
      the International Commission on Radiation Protection (ICRP), subdivides the
      conducting airways into a bronchial (BB) and bronchiolar (bb) part. Preliminary
      results were generated with MS-Excel from deposition data of 1-mummass median
      aerodynamic diameter (MMAD) particles, calculating local slow clearance fractions
      according to mathematical procedures introduced in previous publications. While
      mucociliary clearance is completely finished within 24h after exposure, slow
      clearance takes place in distinct phases and needs several days to weeks. This
      multi-stage event is also reflected in the respective retention curves which
      correspond well to previously published graphs.

PMID- 16895726
TI  - Error bounds for data-driven models of dynamical systems.
AB  - This work provides a technique for estimating error bounds about the predictions
      of data-driven models of dynamical systems. The bootstrap technique is applied to
      predictions from a set of dynamical system models, rather than from the time
      series data, to estimate the reliability (in the form of prediction intervals)
      for each prediction. The technique is illustrated using human core temperature
      data, modeled by a hybrid (autoregressive plus first principles) approach. The
      temperature prediction intervals obtained are in agreement with those from the
      Camp-Meidell inequality. Moreover, as expected, the prediction intervals increase
      with the prediction horizon, time-series data variability, and model inaccuracy.

PMID- 16895727
TI  - Minimally invasive locking plate osteosynthesis for fractures of the distal tibia
      -results in 20 patients.
AB  - AIMS: We report our experiences with minimally invasive locking plate
      osteosynthesis (MILPO), for distal tibia fractures, with specific reference to
      fracture union and complications encountered. PATIENTS AND METHODS: Twenty
      patients underwent MILPO for open and closed distal tibia fractures between March
      2003 and December 2004. Fractures were classified according to the AO system.
      Open fractures were graded using the Gustilo and Anderson classification and
      closed fractures via the Tscherne classification system. RESULTS: There were 16
      males and 4 females of mean age 44.7 years (range 19-69 years). Thirteen patients
      had temporary external fixation, prior to definitive fracture fixation. Minimum
      follow-up was 12 months and average time to full weight bearing in the closed
      fracture group (12 patients) was 18.1 weeks (range 8-32 weeks) and 19.3 weeks in
      the open fracture group (8 patients, range 8-44 weeks). Fracture healing was
      defined as radiological evidence of bridging mature callus combined with pain
      free full weight bearing. In the open fracture group, four fractures united
      within 6 months, one within 6-12 months and one united 12 months after surgery;
      there were two cases of non-union. In the closed fracture group, seven fractures
      united within 6 months, three fractures between 6 and 12 months and two after 12
      months from surgery. Two of the 20 patients required additional procedures to aid
      bone healing in the post-operative period. Three of the 20 patients required
      metalwork removal, for delayed wound breakdown in two cases and wound infection
      in one case. An uneventful recovery was made following this, in all three cases.
      There was one case of implant failure due to plate breakage at 32 weeks post-op.
      The fracture site was opened and re-plated at 32 weeks with a DCP. There were no
      complications following this. CONCLUSION: MILPO was used for definitive fixation
      of high energy, open and closed, peri-articular distal tibia fractures. This
      approach aims to preserve bone biology and minimise surgical soft tissue trauma.
      This surgical approach may provide an answer to treating a challenging group of
      fractures and further research is warranted.

PMID- 16895728
TI  - Amphetamine depresses excitatory synaptic transmission at prefrontal cortical
      layer V synapses.
AB  - Dopamine modulates the function of glutamatergic synapses in prefrontal cortex,
      modifying synaptic strength and influencing synaptic plasticity. Here we have
      explored the ability of endogenous dopamine, present in slices containing the
      prefrontal cortex, to influence excitatory synaptic transmission. We found that
      10 microM amphetamine, which releases and blocks the reuptake of dopamine from
      dopaminergic nerve terminals, significantly depressed excitatory field potentials
      recorded in layer V during stimulation of layer II/III. The depression was
      reversible, dose dependent and correlated with increased paired pulse
      facilitation, suggesting that amphetamine inhibits the presynaptic release of
      glutamate. Pharmacological dissection of this response showed that dopamine D1
      receptors are likely to mediate the effects of endogenous dopamine on excitatory
      synaptic transmission, with little effect of alpha2 adrenergic receptors,
      serotonin receptors, or D2 dopamine receptors. The time to peak amphetamine
      effect was longer than expected based on diffusion, suggesting that to raise
      dopamine levels in brain slices amphetamine may need to be transported into the
      presynaptic terminals. These results provide evidence that D1/D5 receptors
      depress glutamate release at this cortical synapse, and suggest that amphetamine
      will have profound and persistent effects on PFC functioning in vivo.
      Dysregulation of this mechanism could contribute to the impairment in cognitive
      performance associated with abnormal PFC dopamine receptor activation.

PMID- 16895729
TI  - Dehydroepiandrosterone sulfate prevents ischemia-induced impairment of long-term
      potentiation in rat hippocampal CA1 by up-regulating tyrosine phosphorylation of
      NMDA receptor.
AB  - We have reported that dehydroepiandrosterone sulfate (DHEAS) reduces the
      threshold for long-term potentiation (LTP) in Shaffer collateral-CA1 synapses
      through the amplification of Src-dependent NMDA receptor signaling. The present
      study is a follow-up of the above reports, aiming at evaluating the effects of
      DHEAS on the impaired LTP in reversible forebrain ischemic rats. Transient (20
      min) incomplete forebrain ischemia led to an impaired LTP in the hippocampal CA1
      region without damages to the basal synaptic transmission between the Shaffer
      collaterals and pyramidal neurons. Repetitive administrations of DHEAS (20 mg/kg
      for 3 days) from the first 3 h of reperfusion, but not acute DHEAS application
      (50 microM), prevent the impairment of LTP produced by ischemia. Co
      administration of the specific sigma(1) receptor antagonist NE100 with DHEAS
      completely prevented the protective effect of DHEAS. In contrast, progesterone
      (PRGO) not only had no protective effect against the ischemic LTP impairment, but
      also attenuated the protective effect of DHEAS on the impaired LTP. Tyrosine
      phosphorylation of NMDA receptor subunit 2B (NR2B) significantly decreased after
      ischemia, whereas that of NR1 had no obvious change. Furthermore, the repetitive
      administration of DHEAS improved the reduction in tyrosine phosphorylation of
      NR2B. These findings suggest that the repetitive activation of sigma(1) receptor
      induced by DHEAS might prevent the ischemic LTP impairment through regulating the
      tyrosine phosphorylation of NR2B.

PMID- 16895730
TI  - Warmer preparation of hippocampal slices prevents synapse proliferation that
      might obscure LTP-related structural plasticity.
AB  - The hippocampal slice is a popular model system in which to study the cellular
      properties of long-term potentiation (LTP). Synaptogenesis induced by exposure to
      ice-cold artificial cerebrospinal fluid (ACSF), however, raises the concern that
      morphological correlates of LTP might be obscured, especially in mature slices.
      Here we demonstrate that preparation of mature hippocampal slices at room
      temperature (approximately 25 degrees C) maintains excellent ultrastructure and a
      synapse density comparable to perfusion-fixed hippocampus. These results suggest
      that slices prepared at room temperature might provide a better basis from which
      to detect LTP-related changes in synapse number and morphology.

PMID- 16895731
TI  - Presynaptic inhibition by kainate receptors converges mechanistically with
      presynaptic inhibition by adenosine and GABAB receptors.
AB  - Kainate receptors are widely reported to regulate the release of neurotransmitter
      in the CNS, but the mechanisms involved remain controversial. Previous studies
      have found that the kainate receptor agonist ATPA, which selectively activates
      Glu(K5)-containing kainate receptors, depresses glutamate release at Schaffer
      collateral synapses in the hippocampus. In the present study, we provide
      pharmacological evidence that this depressant effect is mediated by Glu(K5)
      containing heteromers, but is distinct from a similar depressant effect engaged
      by the kainate receptor agonist domoate. The depressant effect of ATPA is
      insensitive to antagonists for GABA(A), GABA(B), and adenosine receptors, and is
      also unaffected by lowering the release probability by reducing extracellular
      calcium. However, the effect of ATPA is partly occluded by prior activation of
      GABA(B) receptors and completely occluded by prior activation of adenosine
      receptors, suggesting a mechanistic convergence of heteromeric Glu(K5) kainate
      receptor signaling with GABA(B) receptors and adenosine receptors. The effects of
      domoate are partially occluded by both adenosine and GABA(B) receptor agonists,
      indicating at least a partial convergence of Glu(K5)-lacking kainate receptor
      signaling with these other pathways. The depressant effect of ATPA is not blocked
      by inhibition of serine/threonine protein kinases. These results suggest that
      ATPA and domoate inhibit glutamate release through mechanisms that converge with
      those of classical metabotropic receptor agonists, although they do so through
      different receptors.

PMID- 16895732
TI  - The cannabinoid receptor agonist WIN 55,212-2 attenuates the effects induced by
      quinolinic acid in the rat striatum.
AB  - The ability of CB(1) receptors to regulate the release of glutamate in the
      striatum, together with the finding that, in experimental models of Huntington
      disease (HD), both endocannabinoid levels and CB(1) receptor densities are
      reduced, has prompted the investigation on the neuroprotective role of the
      cannabinoids in HD. Quinolinic acid (QA) is an excitotoxin that, when injected in
      the rat striatum reproduces many features of HD and that acts by stimulating
      glutamate outflow. The aim of the present study was to test the ability of the
      cannabinoid receptor agonist WIN 55,212-2 to prevent the effects induced by QA in
      the rat striatum. In microdialysis experiments, probe perfusion with WIN 55,212-2
      significantly and dose-dependently prevented the increase in extracellular
      glutamate induced by QA. In electrophysiological recordings in corticostriatal
      slices, the application of WIN 55,212-2 prevented QA-induced reduction of the
      field potential amplitude. Both effects of WIN 55,212-2 were prevented by the
      CB(1) receptor antagonist AM 251. In in vivo experiments, intrastriatal WIN
      55,212-2 significantly attenuated the striatal damage induced by QA, although no
      significant effects were observed on a behavioural ground. These data demonstrate
      that the stimulation of CB(1) receptors might lead to neuroprotective effects
      against excitotoxic striatal toxicity.

PMID- 16895733
TI  - Multiple forms of long-term plasticity at unitary neocortical layer 5 synapses.
AB  - Long-term potentiation and depression (LTP and LTD) are cellular plasticity
      phenomena expressed at a variety of central synapses, and are thought to
      contribute to learning and developmental changes in circuitry. Recurrent
      neocortical layer-5 synapses are thought to express a presynaptic form of LTP
      that influences the short-term plasticity of the synapse. Here we show that
      changes in synaptic strength elicited by pairing high frequency pre- and
      postsynaptic firing at this synapse result from a mixture of presynaptic and
      postsynaptic forms of plasticity, as assessed by the analysis of changes in
      coefficient of variation, short-term plasticity, and NMDA:AMPA current ratios.
      Pharmacological dissection of this plasticity revealed that block of presynaptic
      LTD with an endocannabinoid inhibitor enhanced LTP, while the apparently
      presynaptic component of LTP could be prevented by induction in the presence of
      blockers of nitric oxide. These data suggest that correlated high-frequency
      firing at layer-5 synapses simultaneously induces a mixture of presynaptic LTD,
      presynaptic LTP, and postsynaptic LTP.

PMID- 16895734
TI  - Activity-dependent regulation of NR2B translation contributes to metaplasticity
      in mouse visual cortex.
AB  - Visual experience and deprivation bidirectionally modify the NR2A and NR2B
      subunit composition of NMDARs, and these changes in turn modify the properties of
      synaptic plasticity in the visual cortex. Deprivation-induced lowering of the
      NR2A/2B ratio can occur by altering either NR2A or NR2B protein levels, but how a
      reduction in synaptic activity regulates these changes in a subunit-specific
      manner is poorly understood. Here, we find that visual deprivation in juvenile
      mice by dark-rearing or monocular lid suture reduces the NR2A/2B ratio in the
      deprived cortex in temporally distinct phases--initially by increasing NR2B
      protein levels, and later by decreasing NR2A protein levels. Brief dark-exposure
      of juvenile rats likewise produces an increase in NR2B expression. Furthermore,
      we are able to model the early increase in NR2B by blocking NMDARs in vitro, and
      we find that translation of NR2B is likely a major point of regulation.
      Translation of NR2A is not regulated in this manner. Therefore, the differential
      translational regulation of NR2A and NR2B may contribute to experience-dependent
      modification of NMDAR subunit composition.

PMID- 16895735
TI  - Trends in overweight and obesity in Portuguese conscripts from 1986 to 2000 in
      relation to place of residence and educational level.
AB  - OBJECTIVE: The aim of this study was to analyse changes in the prevalence of
      overweight and obesity between 1986 and 2000 in Portuguese conscripts, and to
      examine the role of place of residence and educational level. STUDY DESIGN: Cross
      sectional study. METHODS: Data sets from the cross-sectional annual surveys of
      all 18-year-old Portuguese males born between 1966 and 1981 and examined between
      1986 and 2000 (850 081 subjects) were used in this study. Height and weight were
      measured and body mass index was calculated. Data on educational level (4, 6, 9,
      11 and 12+ years) and residence (urban, semi-urban and rural) were collected.
      RESULTS: The prevalence of overweight increased from 10.5% in 1986 to 21.3% in
      2000, and the prevalence of obesity increased from 0.9% to 4.2% in the same
      period (P<0.001). After adjustment for year of examination, the odds ratio (OR)
      for being overweight increased with educational level (reference 4-6 years: 1.19;
      9 years: 1.30; 11 years: 1.47; 12+ years: 2.41) and place of residence (reference
      urban-semi-urban: 1.04; rural: 1.06). The prevalence of obesity increased with
      educational level (reference 4-6 years: 1.27; 9 years: 1.79; 11 years: 1.83; 12+
      years: 2.66) and decreased with place of residence, i.e. those who lived in rural
      areas had a lower risk of becoming obese (OR: 0.94). CONCLUSIONS: Despite the low
      prevalence of obesity in young males in Portugal compared with other European
      countries, the sharp increase in recent years indicates that public health
      strategies are needed to prevent obesity.

PMID- 16895736
TI  - Bone and cartilage tissue constructs grown using human bone marrow stromal cells,
      silk scaffolds and rotating bioreactors.
AB  - Human bone marrow contains a population of bone marrow stromal cells (hBMSCs)
      capable of forming several types of mesenchymal tissues, including bone and
      cartilage. The present study was designed to test whether large cartilaginous and
      bone-like tissue constructs can be selectively engineered using the same cell
      population (hBMSCs), the same scaffold type (porous silk) and same hydrodynamic
      environment (construct settling in rotating bioreactors), by varying the medium
      composition (chondrogenic vs. osteogenic differentiation factors). The hBMSCs
      were harvested, expanded and characterized with respect to their differentiation
      potential and population distribution. Passage two cells were seeded on scaffolds
      and cultured for 5 weeks in bioreactors using osteogenic, chondrogenic or control
      medium. The three media yielded constructs with comparable wet weights and
      compressive moduli ( approximately 25 kPa). Chondrogenic medium yielded
      constructs with higher amounts of DNA (1.5-fold) and glycosaminoglycans (GAG, 4
      fold) per unit wet weight (ww) than control medium. In contrast, osteogenic
      medium yielded constructs with higher dry weight (1.6-fold), alkaline phosphatase
      (AP) activity (8-fold) and calcium content (100-fold) per unit ww than control
      medium. Chondrogenic medium yielded constructs that were weakly positive for GAG
      by contrast-enhanced MRI and alcian blue stain, whereas osteogenic medium yielded
      constructs that were highly mineralized by microCT and von Kossa stain.
      Engineered bone constructs were large (8mm diameter x 2mm thick disks) and
      resembled trabecular bone with respect to structure and mineralized tissue volume
      fraction (12%).

PMID- 16895737
TI  - Robot-assisted hindlimb extension increases the probability of swing initiation
      during treadmill walking by spinal cord contused rats.
AB  - Training and evaluation of locomotion in animals with spinal cord injury will
      likely be improved with the development of techniques that increase stepping
      activity. We hypothesized that robot-assisted extension of the hindlimbs of
      spinal cord injured rats during stance would increase the probability that the
      swing phase of gait would be initiated. Thirty-three adult, Sprague-Dawley rats
      received a contusion injury to the mid-thoracic spinal cord. The animals'
      hindlimbs were pulled into extension using small robotic arms to pull at the
      ankle, as the rat stepped on either a reciprocating, robotic paw platform or a
      conventional treadmill belt. The animals demonstrated an increase in the
      probability of swing initiation with spontaneous recovery during the first 4
      weeks following injury (p < 0.0001). The probability of swing initiation was
      found to be greater with the use of robot-assisted extension versus no extension
      force at the ankle (75+/-16.9% versus 38.9+/-16.6%, p < 0.001). Swing initiation
      occurred most frequently at a particular distance of hindlimb extension (50 mm
      caudal from the neutral position at stance), but was broadly tuned about this
      distance. These results indicate that a greater amount of stepping activity can
      be elicited by robot-assisted extension, thereby providing possible benefits to
      evaluation and training of gait following SCI.

PMID- 16895738
TI  - Nosocomial outbreak of Pseudomonas aeruginosa infections related to a flexible
      bronchoscope.
AB  - An outbreak of Pseudomonas aeruginosa infections affecting 17 patients was
      detected in the 27-bed intensive care unit (ICU) of a community hospital from 1
      July to 30 September 2003. An ambidirectional cohort study was conducted to
      identify the risk factors for infection. Nosocomial infections were defined using
      the criteria of the Centers for Disease Control and Prevention. Random arbitrary
      polymorphic DNA-polymerase chain reaction was used for genotypic
      characterization. Logistic regression analyses demonstrated that case patients
      were more likely than non-cases to have had a longer stay in the ICU, and to have
      undergone mechanical ventilation and antimicrobial treatment. The multi-variate
      analysis identified recent bronchoscopy [risk ratio (RR) 3.8, 95% confidence
      interval (CI) 2.5-3.9] and exposure to an infected patient (RR 2.9, 95% CI 1.1
      3.7) as independent risk factors. Molecular analysis showed that of the nine
      isolates available, four patients had a similar strain. The factor with the
      strongest influence on the risk of death was infection with P. aeruginosa (RR
      2.1, 95% CI 1.0-2.4, P=0.04). A combined infection control strategy was
      implemented, including strict compliance with isolation precautions and
      recommendations for cleaning and disinfecting bronchoscopes, and a sharp
      reduction in the incidence of P. aeruginosa infection followed. It is thought
      that this outbreak was caused by patient-to-patient transmission and infection
      from a common source, i.e. the flexible bronchoscope.

PMID- 16895740
TI  - Stomatal conductance of semi-natural Mediterranean grasslands: implications for
      the development of ozone critical levels.
AB  - Intra-genus and intra-specific variation and the influence of nitrogen enrichment
      on net assimilation and stomatal conductance of some annual Trifolium species of
      Mediterranean dehesa grasslands were assessed under experimental conditions. Also
      gas exchange rates were compared between some Leguminosae and Poaceae species
      growing in the field in a dehesa ecosystem in central Spain. The results showed
      that the previously reported different O3 sensitivity of some Trifolium species
      growing in pots does not seem to be related to different maximum g(s) values. In
      addition, no clear differences on gas exchange rates could be attributed to
      Leguminosae and Poaceae families growing in the field, with intra-genus variation
      being more important than differences found between families. Further studies are
      needed to increase the database for developing a flux-based approach for setting
      O3 critical levels for semi-natural Mediterranean species.

PMID- 16895739
TI  - Quantitative evaluation of prion inactivation comparing steam sterilization and
      chemical sterilants: proposed method for test standardization.
AB  - Prions are notoriously resistant to inactivation. To prevent accidental
      transmission of variant Creutzfeldt-Jakob disease (vCJD), various decontamination
      procedures have been adopted for re-usable medical devices by the authorities of
      countries at risk. As the vCJD agent in humans has a wide tissue distribution,
      practical methods of prion decontamination urgently need to be standardized, as
      do other sterilization and disinfection procedures (European Committee for
      Standardization). This article proposes a method using a quantitative murine
      model, combining observations of the decrease in the infection rate, the increase
      in the incubation period and a simultaneously performed chemical protein fixation
      control. In terms of practical application, autoclaving at 134 degrees C for 18
      min or 121 degrees C for 30 min, and 1N sodium hydroxide for 15 min reduced the
      transmission of infectivity by a factor of at least 10(6). Partial efficacy can
      also be identified by the methodology, particularly for liquid cold sterilants
      such as glutaraldehyde and peracetic acid solutions.

PMID- 16895742
TI  - Determining algal-available phosphorus in pulp and paper mill effluents: algal
      assays vs routine phosphorus analyses.
AB  - We determined the potentially algal-available P (P(aa)) in pulp and paper mill
      effluents by two bioassay techniques (a dual-culture assay and a batch approach)
      and compared it with chemically analysed P (total P, total dissolved P, reactive
      P, dissolved reactive P and dissolved hydrolysable P). The mean P(aa) given by
      the dual-culture assay was within a 40% range of that given by the batch
      approach. The P(aa) obtained by both bioassays differed from total P. Dissolved
      reactive P appeared to be the most readily available chemical P fraction, but
      other P fractions also contributed to P(aa). The analysis of reactive P, which
      involves direct staining of an unfiltered sample, best approximated the P(aa)
      given by the dual-culture assay (relative error 9%). The results suggest that
      assessment of eutrophying effluent P can be improved by analysing simple chemical
      P fractions in wastewater. The fractions to be analysed, however, may be site
      specific.

PMID- 16895741
TI  - Vegetable and synthetic tannins induce hormesis/toxicity in sea urchin early
      development and in algal growth.
AB  - Mimosa tannin and phenol-based synthetic tannin (syntan) were tested for toxicity
      to sea urchin (Paracentrotus lividus and Sphaerechinus granularis) early
      development and to marine algal growth (Dunaliella tertiolecta). Sea urchin
      embryogenesis was affected by vegetable tannin and syntan water extracts (VTWE
      and STWE) at levels >or=1mg/L. Developmental defects were significantly decreased
      at VTWE and STWE levels of 0.1 and 0.3mg/L when control cultures displayed
      suboptimal quality, i.e. <70% "viable" (normal or retarded) larvae. Fertilization
      success of sea urchin sperm was increased up to 0.3 mg/L STWE or VTWE, then was
      inhibited by increasing tannin levels (1-30 mg/L). Offspring abnormalities,
      following sperm exposure to VTWE or STWE, showed the same shift from hormesis to
      toxicity. Cell growth bioassays in D. tertiolecta exposed to VTWE or STWE (0.1-30
      mg/L) showed non-linear concentration-related toxicity. Novel criteria are
      suggested in defining control quality that should reveal hormetic effects.

PMID- 16895743
TI  - Effect of amendments on the extractability, retention and plant uptake of metals
      on a sewage-irrigated soil.
AB  - Laboratory and greenhouse experiments were conducted to evaluate the effects of
      farmyard manure (FYM), CaCO(3) and single superphosphate (SSP) on retention and
      availability of Zn, Cu and Ni in sewage-irrigated soil. We also assessed the
      suitability of 0.05M EDTA for predicting the effectiveness of these amendments in
      reducing the phytoavailability of metals. Results indicated that EDTA could
      successfully predict the phytoavailability of Zn and Ni in amended soil, whereas
      it failed in case of Cu. By and large, application of CaCO(3), either alone or in
      combination with FYM had a positive effect on the retention of Zn, Cu and Ni in
      soil. Application of CaCO(3) alone or in combination with FYM was equally
      effective in reducing the Zn content in lettuce, whereas sole application of
      CaCO(3) significantly reduced Ni content. However, only SSP was found to be
      effective in reducing the Cu content in lettuce.

PMID- 16895744
TI  - Ultrasonographic and Doppler velocimetric evaluation of the levator ani muscle in
      premenopausal women with and without urinary stress incontinence.
AB  - OBJECTIVES: The objective was to evaluate the cross-sectional area (CSA) and the
      Doppler velocimetric parameters of the levator ani muscle vessels in
      premenopausal women with and without urinary stress incontinence. STUDY DESIGN:
      Sixty-three premenopausal women constituted three groups: GI (nulliparous), GII
      (continent multiparous), and GIII (incontinent multiparous). The patients had
      undergone transperineal ultrasound in which the CSA was measured and Doppler
      velocimetry was performed. The examination was repeated by a second observer
      using the same procedure. RESULTS: There was a statistically significant
      correlation between the measurements of the observers I and II regarding all the
      parameters studied, except for the A/B ratio in GIII. The CSA was significantly
      greater in GI and GII than in GIII. As far as Doppler velocimetry is concerned
      there were no differences in the Doppler velocimetric indices among the three
      groups. Concerning the absent end diastolic shift, it was observed that there was
      a significantly greater incidence of such findings in GI+GII (continent women)
      towards GIII (incontinent women). CONCLUSIONS: The CSA evaluation and the Doppler
      velocimetry of the levator ani muscle vessels were highly reproducible. The CSA
      was higher in continent women and the frequency of the absent end diastolic shift
      was higher in incontinent women.

PMID- 16895745
TI  - Reduced fertility and inability of oocytes to resume meiosis in mice deficient of
      the Lxr genes.
AB  - Cholesterol precursors act as activators of the nuclear hormone receptor, liver X
      receptor (LXR). One of these LXR-activating ligands is meiosis activating sterol
      (MAS), which also induces resumption of meiosis in oocytes from mice in vitro.
      Whether LXR participates in the regulation of oocyte maturation and whether the
      expression of either one of the two paralogues of LXR (alpha and beta) affect
      fertility of mice has, however, not yet been clarified. Female mice lacking Lxra,
      Lxrb or both genes (Lxra(-/-), Lxrb(-/-) and Lxrab(-/-), respectively) conceive
      less frequently and have significantly fewer pups per litter as compared to wild
      type mice. Both Lxra and Lxrb mRNA were found to be expressed in mouse oocytes.
      The relative expression of, in particular, Lxrb was almost two orders of
      magnitude higher than in liver, brain and testis. A water-soluble LXR agonist
      caused naked oocytes, but not cumulus enclosed oocytes (CEO), from wild type mice
      to resume meiosis significantly more often than control oocytes. Follicle
      stimulating hormone (FSH) is a potent stimulator of meiosis in CEO from wild type
      mice, but was without effect in mice lacking both Lxr genes. Zymosterol, a MAS
      active substance, induced resumption of meiosis in oocytes from Lxrab(-/-) mice,
      but significantly less effectively than in oocytes from wild type mice. Taken
      together, LXRs seem to affect ovarian function, suggesting specific roles of
      cholesterol precursors in regulation of female reproduction.

PMID- 16895746
TI  - Serum thyroid hormones and performance of offspring in ewes receiving
      propylthiouracil with or without melatonin.
AB  - Two experiments were conducted during mid-gestation to examine effects in ewes of
      propylthiouracil (PTU) treatment alone or with melatonin on serum thyroid
      hormones, postpartum reproduction, and lamb performance. In the first experiment,
      beginning on day 0 (first day of treatment when all animals were 72.2+/-0.9 days
      of gestation), ewes received daily treatments (gavage) consisting of either 0mg
      (n=6) or 40 mg (n=6) PTU/kg body weight/day for 15 days. After 15 days, the 40 mg
      dosage was decreased to 20mg/kg body weight for an additional 20 days (35 days of
      PTU). Serum thyroxine (T4) did not differ (P>0.10) between groups through day 4;
      but on day 5, control females had a serum value of 67 ng/ml compared with 46 (+/
      5)ng/ml for PTU-treated ewes (P=0.02). On the last day that 40 mg of PTU was
      administered, serum T4 averaged 67 and 7 (+/-5)ng/ml (P<0.001) in the two
      respective groups. Serum T4 remained low and was 80 and 1 ng/ml (P<0.001) in
      control and treated ewes on day 34. Serum T4 rose gradually after PTU but
      remained different from that observed in control ewes through day 48. Lambs from
      control and treated ewes had similar (P=0.46) T4 values at birth but lambs from
      PTU-treated ewes had lower (P=0.03) birth weights than did those from control
      ewes. Serum progesterone (P4) after parturition indicated a lack of cyclicity in
      all ewes. In the second experiment, beginning on day 0 (76.8+/-4.7 days of
      gestation), ewes received PTU as in Experiment 1. In addition, after 15 days of
      PTU, melatonin was given (i.m. injections at 5mg/day) for 30 days.
      Propylthiouracil decreased (P<or=0.05) serum T4 on days 25 through 41 of the
      treatment period. Serum T3 was lower (P<0.05) in PTU-treated ewes from day 8
      through the end of PTU administration. Postpartum P4 was below 1 ng/ml on all
      days indicating acyclicity. Lamb body weight and serum IGF-I were similar
      (P>0.60) for lambs born to control and treated ewes. Female offspring of
      PTU+melatonin-treated dams reached puberty, became anestrus, and returned to
      cyclicity at similar (P>0.10) times to contemporary ewe lambs. Results indicate
      that 40/20mg PTU alone or with melatonin does not induce cyclicity after lambing
      in spring lambing ewes and has little effect on offspring performance.

PMID- 16895747
TI  - Ultra-structural changes and developmental potential of porcine oocytes following
      vitrification.
AB  - This study evaluated the effects of exposure and/or vitrification of porcine
      metaphase II (MII) oocytes on their in vitro viability and ultra-structural
      changes with two experiments. Experiment 1 examined the effect of vitrified
      oocytes on microtubule localization, mitochondrial morphology, chromosome
      organization and the developmental rate in IVF control and vitrified oocytes.
      Oocytes matured for 44 h were subjected to IVF (IVF control). Oocytes matured for
      42 h were exposed to cryoprotectants (CPA control), followed by 2h culture, and
      subjected to IVF. Oocytes vitrified at 42 h post-maturation were warmed, cultured
      for 2h, and subjected to IVF (vitrified). Experiment 2 evaluated the effect of
      oocytes freezing on development of ICSI with and without activation and
      parthenotes. Fresh and vitrified oocytes were subjected to ICSI with and without
      electrical activation. Cleavage and blastocyst rates were significantly (P<0.05)
      lower in vitrified IVF, parthenote and ICSI embryos than those in fresh
      counterparts. Between ICSI embryos from fresh oocytes and vitrified oocytes, the
      rates of blastocyst were significantly higher (P<0.05) in activated group than
      the group without activation. Significant differences (P<0.05) were observed in
      normal spindle configuration of vitrified (43.5%) compared to control (81.0%)
      oocytes, but no significant difference was observed between CPA exposed and
      control groups. In conclusion, porcine oocytes at MII stage are very sensitive to
      vitrification with altered microtubule localization and mitochondrial
      organization thus resulting in impaired fertilization and embryo development.

PMID- 16895748
TI  - Pleomorphic adenoma of the nasal septum and its relationship with Epstein-Barr
      virus.
AB  - OBJECTIVES: Pleomorphic adenoma is the most common benign tumor of the major
      salivary glands, especially of the parotid gland. It is much less common in the
      minor salivary glands of the oral cavity, and it rarely occurs in others sites in
      the head and neck. Even if virus involvement in salivary glands tumor has been
      many times discuted, the etiology of this tumor keeps being unknown. As compared
      to other nasal tumors, we tried to prove if Epstein-Barr virus (EBV) could be
      involved in the development of pleomorphic adenoma in this particular nasal
      localization. METHODS: Three cases of pleomorphic adenomas of the nasal septum
      (two women and a man in age of 23-59 years) were retrospectively studied. All had
      positive rate of EBV-related blood antibodies. All the patients had undergone
      endoscopic surgery to remove the complete tumor. We used hybridation technique in
      the search for EBV-DNA in the three tumors. RESULTS AND CONCLUSION: We had
      positive EBV-DNA detection in the tumor in one case, which seemed to prove
      relationship between pleomorphic adenoma and this virus. The literature
      concerning the subject is reviewed in order to explain EBV involvement in the
      development of such tumors in this particular localization.

PMID- 16895750
TI  - Genetically determined imbalance between serum levels of tumour necrosis factor
      (TNF) and interleukin (IL)-10 is associated with anti-Jo-1 and anti-Ro52
      autoantibodies in patients with poly- and dermatomyositis.
AB  - Our aim was to investigate presence of tumour necrosis factor (TNF) and
      interleukin (IL)-10 in serum and their relation to different genotypes as well as
      to clinical and laboratory phenotypes in patients with polymyositis and
      dermatomyositis. In 65 patients with poly- or dermatomyositis the inflammatory
      cytokine balance was evaluated by the assessing absolute levels as well as the
      ratio between TNF and IL-10 in serum. These levels were correlated to the G-308A
      TNFA, G-1087A IL10 and G915C TGFB1 gene polymorphisms and haplotype frequencies,
      gender, autoantibody profiles and clinical manifestations. Increased serum levels
      of TNF and IL-10 were observed in patients compared to controls. A significantly
      higher TNF:IL-10 ratio was detected in female poly- and dermatomyositis patients
      carrying the TNF2 allele compared to female patients with the TNF1/TNF1 genotype
      (median+/-IQR 1.513+/-0.0.679 vs. 0.950+/-1.173, p=0.021). This ratio was also
      significantly higher in patients with the extended MICA5.1/TNF2/TNFa2/DRB1*03
      haplotype compared to patients lacking this haplotype. A significantly higher
      TNF:IL-10 ratio was recorded in sera of patients with anti-Ro52 (1.513+/-1.275
      and 1.276+/-0.671, positive vs. negative, p=0.010) antibodies and in women with
      anti-Jo-1 (1.919+/-0.918 and 1.281+/-0.790, positive vs. negative, p=0.041). Our
      data suggest that a genetically programmed cytokine imbalance exists in patients
      with poly- or dermatomyositis and that this imbalance is related to the presence
      of disease-associated autoantibodies.

PMID- 16895751
TI  - Metabolic syndrome in young adults from two socioeconomic Latin American
      settings.
AB  - BACKGROUND AND AIM: Since little information on the metabolic syndrome (MS) is
      available in Latin America, the aim of this study was to explore whether and to
      what extent differing socioeconomic conditions influence the prevalence of MS and
      its associated factors among young adults from two towns in Latin America: semi
      rural Limache (L), Chile, and urban Ribeirao Preto (RP), Brazil. METHODS AND
      RESULTS: A cross-sectional study based on two independent investigations of 22-
      to 28 year-old subjects using a common methodology. The prevalence of MS
      (according to the US National Cholesterol Education Program) and its risk factors
      (smoking habit, alcohol and caloric intake, obesity, physical activity and
      socioeconomic conditions) were assessed. The prevalence of MS was 10% in L and in
      RP men, but was lower (4.8%) in RP women. Hyperglycemia was very low (0.8% in L
      and 1.1% in RP), while the prevalence of low HDL cholesterol levels was high
      (66.7% and 42.2%, respectively). Intermediate prevalences of hypertriglyceridemia
      (17.9% and 12.9%), elevated blood pressure (15.5% and 23.1%) and abdominal
      obesity (19.3% versus 12.7%) were detected. RP subjects had a higher educational
      level and more qualified jobs, came from smaller families, and a higher
      proportion were car owners. In L, the smoking habit was more frequent, subjects
      had higher excess weight and caloric intake, and lower levels of physical
      activity. CONCLUSIONS: Metabolic changes possibly leading to cardiovascular
      diseases in later life were present in both populations at an early age, but were
      higher in the rural and less developed county. Our findings point to the
      existence of a cultural, educational and socioeconomic phenomenon that possibly
      influences the prevalence of the diagnostic components of MS through differences
      in lifestyles.

PMID- 16895752
TI  - Double umbilical cord blood transplantation.
AB  - Unrelated umbilical cord blood (UCB) is an alternative donor source for
      allogeneic haematopoietic cell transplantation and, compared with unrelated donor
      bone marrow, has the advantages of rapid availability, greater tolerance of HLA
      disparity and lower incidence of severe graft-versus-host disease. Graft cell
      dose is an important determinant of haematopoietic recovery and overall outcome
      following UCB transplantation, and the limited cell dose of single UCB units has
      been a major barrier to its more widespread use. Transplantation with two
      unrelated UCB units is feasible, safe and effective and can overcome the
      limitation of cell dose of single UCB units.

PMID- 16895753
TI  - Glomerella truncata sp. nov., the teleomorph of Colletotrichum truncatum.
AB  - Anthracnose of lentil, caused by Colletotrichum truncatum is a serious threat to
      lentil (Lens culinaris) grown in western Canada. The teleomorph stage of this
      pathogen was induced to form under laboratory conditions. Random pairing of
      single conidium isolates enabled the identification of fertile isolates. The
      individual isolates of this fertile pair were crossed with 14 other isolates, and
      all isolates were also incubated alone. Self-sterility was observed for all 16
      isolates tested. Three isolates did not produce perithecia with either tester
      isolate, and none of the isolates tested produced perithecia with both tester
      isolates. Perithecia were brown-black, superficial, solitary or in small groups,
      obpyriform to ovate or ampulliform, 200-520 x 110-320 microm (mean: 350 x 200
      microm). Asci were cylindrical, narrowing slightly at the apex, unitunicate,
      evanescent, 53-142 x 5-14 microm (mean: 90 x 8 microm), and contained eight
      ascospores. Ascospores were hyaline, aseptate, oblong, 12-20 x 5-8 microm (mean:
      15.7-6.7 microm). The characteristics agree with those described for the genus
      Glomerella, and the species was named G. truncata sp. nov. The morphology of the
      new species is compared with that of other species in the genus, and future
      research on G. truncata is described.

PMID- 16895754
TI  - An attempt at data verification in the EACTS Congenital Database: data before and
      after verification differ significantly.

PMID- 16895756
TI  - Common referent versus shifting referent methods when using case-control data to
      examine patterns of incidence across multiple exposure variables.
AB  - PURPOSE: In case-control studies, when odds ratios estimate rate ratios or risk
      ratios, trends in odds ratios can reflect trends in incidence in the underlying
      population. METHODS AND RESULTS: In this report, we use an empirical example and
      hypothetical data to compare two methods ("common referent" and "shifting
      referent") for calculating odds ratios from case-control data across multiple
      exposure variables. With common referent methods, a single independent variable
      is constructed from the joint distribution of all exposure variables. With
      shifting referent methods, each stratum-specific trend has its own referent.
      CONCLUSIONS: Using examples involving a single ordinal "trend" variable and a
      dichotomous "stratification" variable, we show that common referent odds ratios
      will reflect the pattern of incidence in the underlying population, whereas odds
      ratios calculated using shifting referent methods will not.

PMID- 16895757
TI  - Do health behaviors moderate the effect of socioeconomic status on metabolic
      syndrome?
AB  - PURPOSE: The purpose of this study is to determine whether the effect of
      socioeconomic factors on metabolic syndrome is influenced by such covariates as
      health behavior and psychosocial factors. METHODS: This study used data collected
      from 4400 households during the 2001 Korea National Health and Nutrition
      Examination Survey. A stratified multistage probability sampling method was
      applied and the final sample included 6601 subjects older than 20 years who had
      completed necessary health examinations. RESULTS: The prevalence of metabolic
      syndrome in Koreans was 25.5% (95% confidence interval [CI], 23.8-27.2) for men
      and 28.7% (95% CI, 27.2-30.2) for women. Analysis of moderator effects showed
      that interactions between education and smoking or exercise status and between
      income and alcohol or smoking status were significant. The significance of the
      interaction terms indicates that health behavior and psychosocial factors
      modified the relationship between socioeconomic factors and metabolic syndrome.
      CONCLUSIONS: Results of this study provide evidence that such behaviors as
      smoking, drinking alcohol, and insufficient exercise contribute to the incidence
      of metabolic syndrome. Changes to higher socioeconomic status may not reduce the
      odds of metabolic syndrome unless behavior also is adapted.

PMID- 16895758
TI  - Chitosan-glycerol phosphate/blood implants elicit hyaline cartilage repair
      integrated with porous subchondral bone in microdrilled rabbit defects.
AB  - OBJECTIVE: We have previously shown that microfractured ovine defects are
      repaired with more hyaline cartilage when the defect is treated with in situ
      solidified implants of chitosan-glycerol phosphate (chitosan-GP) mixed with
      autologous whole blood. The objectives of this study were (1) to characterize
      chitosan-GP/blood clots in vitro, and (2) to develop a rabbit marrow stimulation
      model in order to determine the effects of the chitosan-GP/blood implant and of
      debridement on the formation of incipient cartilage repair tissue. METHODS: Blood
      clots were characterized by histology and in vitro clot retraction tests.
      Bilateral 3.5 x 4 mm trochlear defects debrided into the calcified layer were
      pierced with four microdrill holes and filled with a chitosan-GP/blood implant or
      allowed to bleed freely as a control. At 1 day post-surgery, initial defects were
      characterized by histomorphometry (n=3). After 8 weeks of repair, osteochondral
      repair tissues between or through the drill holes were evaluated by histology,
      histomorphometry, collagen type II expression, and stereology (n=16). RESULTS:
      Chitosan-GP solutions structurally stabilized the blood clots by inhibiting clot
      retraction. Treatment of drilled defects with chitosan-GP/blood clots led to the
      formation of a more integrated and hyaline repair tissue above a more porous and
      vascularized subchondral bone plate compared to drilling alone. Correlation
      analysis of repair tissue between the drill holes revealed that the absence of
      calcified cartilage and the presence of a porous subchondral bone plate were
      predictors of greater repair tissue integration with subchondral bone (P<0.005),
      and of a higher total O'Driscoll score (P<0.005 and P<0.01, respectively).
      CONCLUSIONS: Chitosan-GP/blood implants applied in conjunction with drilling,
      compared to drilling alone, elicited a more hyaline and integrated repair tissue
      associated with a porous subchondral bone replete with blood vessels. Concomitant
      regeneration of a vascularized bone plate during cartilage repair could provide
      progenitors, anabolic factors and nutrients that aid in the formation of hyaline
      cartilage.

PMID- 16895759
TI  - Urine cartilage oligomeric matrix protein (COMP) measurement is useful in
      discriminating the osteoarthritic Thoroughbreds.
AB  - OBJECTIVE: To quantify the urinary concentration of cartilage oligomeric matrix
      protein (COMP), and to evaluate the relationship between urinary COMP
      concentration and the catabolic activity of synovial fluid (SF) in diseased
      horses. METHODS: COMP in horse urine was detected by immunoblotting with a
      monoclonal antibody (mAb; 14G4) raised against equine COMP from articular
      cartilage. Urine and serum samples were obtained from 83 Thoroughbred horses with
      aseptic joint diseases (AJD, 79 horses) or septic joint diseases (SJD, four
      horses) at the time of anesthesia induction, and samples of SF were obtained
      during surgery. Control samples of urine (n=111) were collected from normal
      horses free of any orthopedic diseases after they had been racing. COMP
      concentration was determined in all samples using inhibition enzyme-linked
      immunosorbent assay (ELISA) with mAb 14G4. SF samples were also used for the
      quantification of gelatinase activity. RESULTS: Positive bands of COMP fragments
      were determined on the immunoblots with mAb 14G4. The urinary COMP concentrations
      in AJD and SJD horses (1.02+/-0.75 and 1.55+/-1.17 microg/100mg creatinine,
      respectively) were significantly higher than normal (0.57+/-0.29 microg/100mg
      creatinine). In 55 horses with fractures in the AJD group there was a logarithmic
      relationship (r=-0.45, P<0.001) between the urinary and SF COMP measurements,
      while the urinary COMP level was positively correlated with matrix
      metalloproteinase (MMP)-2 and -9 activities (r=0.30, P<0.05 and r=0.51, P<0.001,
      respectively) in SF. CONCLUSIONS: The urinary COMP assay with mAb 14G4 is useful
      for discriminating horses with osteoarthritis. The higher COMP levels in urine
      from such horses would be indicative of enhanced proteolytic activity, in
      addition to the increased COMP levels in the diseased joints.

PMID- 16895760
TI  - Acridine orange accumulation in acid organelles of normal and vacuolated frog
      skeletal muscle fibres.
AB  - The spatial distribution of acid membrane organelles and their relationships with
      normal and vacuolated transverse tubules has been studied in living frog skeletal
      muscle fibres using confocal microscopy. Acridine orange (AO) was used to
      evaluate acid compartments, while a lipophilic styryl dye, RH 414, was employed
      to stain the membranes of the T-system. AO accumulated in numerous spherical
      granules located near the poles of nuclei and between myofibrils where they were
      arranged in short parallel rows, triplets or pairs. AO granules could be divided
      into three groups: green (monomeric AO), red (aggregated AO), and mixed
      green/red. As demonstrated by lambda-scanning, most granules were mixed. Double
      staining of muscle fibres with AO and RH 414 revealed almost all AO granules
      located near the transverse tubules. Vacuolation of the T-system was induced by
      glycerol loading and subsequent removal. The close juxtaposition of AO granules
      and the T-system was preserved in vacuolated fibres. The lumens of vacuoles did
      not accumulate AO. It is concluded that AO granules represent an accumulation of
      AO in lysosome-related organelles and fragmented Golgi apparatus and a possible
      functional role of the spatial distribution of such acidic compartments is
      discussed.

PMID- 16895761
TI  - Analysis of cycloheximide-induced apoptosis in human leukocytes: fluorescence
      microscopy using annexin V/propidium iodide versus acridin orange/ethidium
      bromide.
AB  - Apoptosis is a highly regulated and programmed cell breakdown process
      characterized by numerous changes. Since it is implicated in many pathological as
      well as physiological processes, it is vital to have reliable methods for
      detecting cell death. In this study, we compared several methods for detecting
      apoptosis and necrosis in human leukocytes. Apoptosis was induced either by
      incubating the cells with various doses of cycloheximide (CHX) or by 312 nm UVB
      irradiation. The methods used for detecting apoptosis were light microscopy (May
      Grunwald-Giemsa and trypan blue staining), fluorescence microscopy (acridin
      orange/ethidium bromide and annexin V/propidium iodide staining) and agarose gel
      electrophoresis of fragmented genomic DNA. Our study showed that CHX-induced
      apoptosis in cultured peripheral blood mononuclear cells but had no effect on
      apoptosis in polymorphonuclear cells, so its effect depends on cell type.
      Evaluation and comparison of the methods for detecting apoptosis showed the
      following. A Giemsa-stained cytospin allows the main morphological
      characteristics of necrotic and apoptotic death to be recognized. Trypan blue
      staining, widely used for estimating cell viability, is valueless for detecting
      apoptosis. Both fluorescence methods provided reliable and reproducible results
      and distinguished clearly between subpopulations of apoptotic cells, and were
      closely intercorrelated. Although applicable to a wide spectrum of cell types,
      agar electrophoresis of extracted DNA cannot be applied to all cell types and
      apoptotic conditions. Generally, microscopic examination of acridin
      orange/ethidium bromide stained cells can be recommended as the most reliable of
      the methods tested.

PMID- 16895763
TI  - Setting the agenda: a new model for collaborative tuberculosis epidemiologic
      research.
AB  - Success in reducing tuberculosis (TB) incidence in developed nations has created
      a paradoxical problem for researchers. In many countries, there are too few cases
      to support the research necessary to maintain and accelerate the decline. We
      describe an approach to applied TB research that supports and focuses efforts of
      researchers at 21 academic, clinical, and governmental sites in two countries.
      The Tuberculosis Epidemiologic Studies Consortium (TBESC), funded by the Centers
      for Disease Control and Prevention (CDC) and by outside sources, conducts
      programmatically relevant epidemiologic, behavioral, economic, laboratory, and
      operational research for TB prevention and control. Our experience may serve as a
      model for other types of applied health care research.

PMID- 16895762
TI  - Transducin subunit stoichiometry and cellular distribution in rod outer segments.
AB  - Transducin is a heterotrimeric GTP-binding protein found in the outer segment of
      vertebrate retinas that links the photoactivation of rhodopsin (R*) with
      activation of a robust type VI cGMP phosphodiesterase (PDE6). Association of the
      alpha subunit of Transducin (G(alphat)) with the beta-gamma complex
      (G(betagamma)) is necessary for interaction of the holoprotein with R* and
      exchange of a GTP for a previously bound GDP. We have investigated the abundances
      of the three Transducin subunits by eluting them from bovine rod outer segment
      membranes by centrifugation under various conditions in vitro. We find that a
      substantial amount of G(betagamma) is eluted from ROS under conditions that do
      not elute G(alphat) and that there is an overall three to fourfold molar excess
      of G(betagamma) to G(alphat) in rod outer segments. These results suggest that
      the production and/or turnover of G(alphat), G(beta), and G(gamma) in the rod
      outer segment are controlled independently.

PMID- 16895764
TI  - Treatments for gynaecological cancers.
AB  - Gynaecological cancers account for a significant amount of morbidity and
      mortality in the world, with varying incidences and outcomes depending on the
      country. These malignancies consist of vulval, vaginal, cervical, endometrial,
      fallopian and ovarian cancers, and account for between 10 and 15% of women's
      cancers. Although mainly a disease of post-menopausal women, when affecting
      younger women, fertility-related consequences exist. Therapeutic interventions
      for gynaecological cancers include surgery, chemotherapy and radiotherapy, with
      combination modalities often required. The basis for certain therapies are
      derived from appropriately conducted randomized clinical trial, whereas in some
      settings, therapy is based on clinical experience and intuition. This review will
      endeavour to focus on the evidence base, though inevitably, non-evidence based
      practice is unavoidable.

PMID- 16895765
TI  - Nonreentrant atrioventricular nodal tachycardia due to triple nodal pathways
      manifested by radiofrequency ablation at coronary sinus ostium.
AB  - We report a case of complex supraventricular tachycardia manifested by
      radiofrequency delivery. Initially, the patient presented with orthodromic
      atrioventricular reentrant tachycardia via a left-sided accessory pathway that
      was successfully eliminated. Atrial tachycardia originating from coronary sinus
      ostium was also induced. Radiofrequency delivery at the coronary sinus ostium
      induced a narrow QRS tachycardia with irregular R-R intervals. A detailed
      analysis explained that the tachycardia could be a nonreentrant mechanism due to
      triple atrioventricular nodal pathways: an atrial excitation evokes double
      ventricular response due to simultaneous activation of the fast and slow
      pathways, and the next one activates ventricle through the intermediate pathway.

PMID- 16895766
TI  - Re: Diagnosis of the posterior MI and RBBB combination: significance of early QRS
      forces in V1-V2.

PMID- 16895768
TI  - Shortened QT interval: a distinctive feature of the dysautonomia of chronic
      fatigue syndrome.
AB  - PURPOSE: Because autonomic nervous functioning is frequently abnormal in chronic
      fatigue syndrome (CFS), we examined whether the corrected QT interval (QTc) in
      CFS differs from QTc in other populations. METHODS: The QTc was calculated at the
      end of 10 minutes of recumbence and the end of 10 minutes of head-up tilt. In a
      pilot study, groups of 15 subjects, CFS, and controls, matched for age and sex,
      were investigated. In a second phase of the study, the QTc was measured in larger
      groups of CFS (n = 30) and control patients (n = 96) not matched for demographic
      features. RESULTS: In the pilot study, the average supine QTc in CFS was 0.371 +/
      0.02 seconds and QTc on tilt, 0.385 +/- 0.02 seconds, significantly shorter than
      in controls (P = .0002 and .0003, respectively). Results of phase II confirmed
      this data. CONCLUSIONS: Relative short QTc intervals are features of the CFS
      related dysautonomia. The significance of this finding is discussed.

PMID- 16895767
TI  - Exercise-induced ventricular tachycardia associated with J point ST-segment
      elevation in inferior leads in a patient without apparent heart disease: a
      variant form of Brugada syndrome?
AB  - Exercise-induced monomorphic ventricular tachycardia originating in the right
      ventricular outflow tract without evidence of structural heart disease can be
      idiopathic or can be the harbinger of structural abnormalities such as
      arrhythmogenic right ventricular dysplasia. Recently, the so-called variant
      Brugada syndrome has been reported in very few cases in the literature and is
      much less electrophysiologically defined in terms of its clinical significance.
      We present the case of a 21-year-old man with exercise-induced monomorphic
      ventricular tachycardia (left bundle-branch block/right axis deviation), without
      detectable structural heart disease, with evidence of J point and ST-segment
      elevation in electrocardiogram leads II, III, and aVF after intravenous
      administration of propafenone. This is followed by a brief discussion on the new
      concept of "variant Brugada syndrome," drug-induced electrocardiographic changes,
      normal-variant repolarization abnormality, and idiopathic right ventricular
      outflow tract tachycardia.

PMID- 16895769
TI  - A simple algorithm for defining the mechanism and the chamber of origin in atrial
      tachycardias.
AB  - INTRODUCTION: Although macroreentrant atrial tachycardia (MRAT) and focal atrial
      tachycardia (FAT) can be successfully cured by catheter ablation, the proper
      diagnosis and treatment of these arrhythmias can still be challenging. AIM: The
      objective of this study is to develop an algorithm allowing rapid diagnosis of
      the mechanism and the chamber of origin of atrial tachycardia based on
      intracardiac catheter recordings from the right atrium and the coronary sinus
      (CS). METHODS: A 2-stepped algorithm was designed: (1) The time of biatrial
      activation expressed as a percentage of the tachycardia cycle length served to
      discriminate FAT from MRAT. (2) In FAT, the direction of activation of the CS
      catheter and the earliest atrial activation were used to define the chamber of
      origin. In MRAT, the time of right atrium activation was determined or
      entrainment was used at different sites. Thirty-two intracardiac recordings were
      reviewed off-line after the algorithm by 4 electrophysiologists blinded to the
      mechanism and the chamber of origin. The results of their analysis were compared
      with the intraoperative diagnosis. RESULTS: The algorithm correctly identified 11
      (100%) of 11 FATs and 19 (90.4%) of 21 MRATs. The site of origin was correctly
      identified in 8 (72.7%) of 11 FATs and in 20 of 21 (95.2%) MRATs. The site of
      origin was misidentified in 3 FATs, all arising from the CS ostium. CONCLUSIONS:
      This algorithm allows rapid discrimination between FAT and MRAT. The chamber of
      origin is detected with a high accuracy in MRAT. However, the earliest atrial
      activation taken as an isolated event is not a good predictor for the chamber of
      origin in FAT arising from the ostium of the CS.

PMID- 16895770
TI  - Specific electrocardiographic markers of P-wave morphology in interatrial block.
AB  - BACKGROUND: Interatrial block (IAB; P waves >/= 110 milliseconds), the conduction
      delay between the right (RA) and left atrium (LA), is depicted on the
      electrocardiogram (ECG) as prolonged, often bifid ("notched"), P waves with
      distinguishable RA and LA components. Although electrophysiologic (EP) studies
      give some insight on how RA and LA components are depicted on the surface ECG in
      normal conduction, few if at all any, have conclusively demonstrated this
      correlation with IAB. Using existing EP knowledge, we investigated if such P-wave
      markers on bedside ECGs exist in IAB and appraised their utility in IAB
      recognition. METHODS: We reviewed the medical records of patients admitted to a
      general hospital from December 1, 2004, to December 15, 2004. Of those, 151
      patients had been admitted for nonacute presentations and were screened with 12
      lead ECGs. Thirty-eight ECGs were excluded for nonsinus and paced rhythms, severe
      motion artifact, errors in lead placement, absence of adequate patient
      identification, and duplicate patient admissions after discharge. The remaining
      113 ECGs were then evaluated for IAB. Sixty-three patients who did not have IAB
      formed the control (group A), whereas of the remaining 50 patients with IAB, 24
      who had past ECGs for comparison formed group B1 and 26 without past ECGs formed
      group B2. Groups were compared for common clinical comorbidities, whereas
      sensitivity and specificity were calculated for significant P-wave markers. P
      values were also calculated, with a value of <.05 considered significant.
      RESULTS: Clinical characteristics of patients in all groups were statistically
      comparable. Overall, almost all P waves in patients with IAB (groups 1 and 2)
      appeared "notched" (94%, P < .0001; sensitivity, 75%; specificity, 94% for IAB
      recognition; positive predictive value, 94%). P-wave RA components were commonly
      depicted as "domes," whereas their LA counterparts formed "spikes" (48%, P <
      .0001; sensitivity 96%; specificity, 70% for IAB recognition). When groups B1 and
      B2 were compared with increased accuracy, more P waves in group B1 were noted to
      have notches and had easily discernible RA and LA components; often, the RA
      duration is longer than the LA duration. In addition, more "dome-and-spike"
      complexes could be determined when past ECGs were present for comparison. These
      markers could be found on any bedside ECG lead in IAB but were predominant on
      leads II and V3 to V6. CONCLUSIONS: Specific noninvasive surface markers such as
      P-wave "dome-and-spike" complexes and "notches" in any lead (predominantly leads
      II and V3-V6) on the bedside ECG could alert clinicians to measure P waves and so
      identify IAB.

PMID- 16895771
TI  - Effect of first ventricular tachycardia cycle length on rate of ventricular
      arrhythmia recurrence in patients with implantable cardioverter-defibrillator.
AB  - BACKGROUND: Some controversies exist regarding the proper treatment of
      hemodynamically tolerated and slow ventricular tachycardia (VT). We intended to
      assess the effect of cycle length of first VT episode on total ventricular
      arrhythmia burden in a cohort of patients with implantable cardioverter
      defibrillator (ICD). METHOD: Between March 2000 and March 2005, 195 patients
      underwent ICD implantation at our center. We included 158 patients (mean age,
      58.3 +/- 12.9 years) with follow-up of 3 months or more in this study. Clinical,
      electrocardiographic, and ICD-stored data and electrograms were collected and
      analyzed. RESULTS: During the follow-up of 16.7 +/- 10.6 months, 45 (28.5%) and
      20 (12.6%) patients received first appropriate ICD therapy for VT and ventricular
      fibrillation, respectively. We divided the 45 patients with VT (based on the
      median value of VT cycle length) into 2 groups. Although patients with VT cycle
      length of less than 350 had higher total mean number of appropriate ICD therapy
      (25 vs 6.3, P = .023), during multivariate regression analysis, only left
      ventricular ejection fraction (EF) of less than 25% (P = .020) was correlated
      with total number of appropriate ICD therapy. First VT cycle length (P = .341),
      QRS duration (P = .126), age (P = .405), underlying heart disease (P = .310),
      indication of ICD implantation (P = .113), and sex (P = .886) have failed to
      predict the total burden of ventricular arrhythmia during the follow-up period.
      CONCLUSION: After adjustment for left ventricular EF, initial VT cycle length per
      se did not confer a lower risk for subsequent ventricular arrhythmia recurrence
      compared with those with faster VT. Left ventricular EF of less than 25% was
      correlated with higher ventricular arrhythmia burden in patients with ICD.

PMID- 16895772
TI  - Interpolated premature ventricular contractions with postponed compensatory
      pauses: a misnomer?
AB  - Selected strips of a Holter recording obtained from a healthy young person with
      rare unifocal premature ventricular contractions (PVCs) were obtained.
      Occasionally, the PVCs were interpolated and showed the phenomenon originally
      named postponed compensatory pause by Langendorf [Am Heart J 1953;46:401]. But
      this is a misnomer because, by definition, interpolated PVCs do not have
      compensatory pauses. Thus, it follows that what does not exist cannot be
      postponed. In reality, the basic manifest feature is a prolongation of the first
      RR interval that follows the interpolated beat. However, in view of its use for
      more than half a century, it is probably best to continue using this terminology,
      but only as long as its underlying mechanism and fundamental manifestations are
      properly understood.

PMID- 16895774
TI  - Teaching electrocardiogram interpretation.

PMID- 16895773
TI  - Effects of rapid and slow potassium repolarization currents and calcium dynamics
      on hysteresis in restitution of action potential duration.
AB  - We used a mathematical model to investigate effects of repolarizing currents
      I(kr) and I(ks), calcium (Ca) current I(CaL), and Ca dynamics in network
      sarcoplasmic reticulum and junctional sarcoplasmic reticulum (JSR) on hysteresis
      in restitution of action potential duration. Enhanced I(kr) increased slope of
      restitution, hysteresis loop thickness, and delay between peaks of diastolic
      intervals and action potential duration. Increase in I(ks) decreased loop
      thickness and peak delay. Decrease in I(CaL) had effects similar to increasing
      I(kr), except slope of restitution decreased markedly. Uptake of Ca into the
      network sarcoplasmic reticulum had less effect on hysteresis than transfer of Ca
      into JSR. Faster transfer of Ca into JSR markedly decreased loop thickness and
      peak delay. Our results provide insight into mechanisms responsible for this
      newly identified property of restitution. Such information will be valuable in
      studies where modification of hysteresis is used to investigate its role in
      arrhythmogenesis.

PMID- 16895777
TI  - Revision tympanoplasty including anterior perforations and lateralization of
      grafts.
AB  - Not long ago, the restoration of a perforated tympanic membrane by grafting over
      an air-containing tympanic cavity seemed impossible. Fortunately, successful
      results are so consistent and universal today that restoration of the tympanic
      membrane is expected, and a failure calls for careful evaluation as to "why". If
      known principles are observed, few complications need occur. Usually,
      complications are the result of either the choice and placement of the graft used
      in the repair, or the presence of unresolved upper respiratory pathology. When
      revision tympanoplasty is necessary, use of the underplay fascial graft
      technique, properly applied, usually can solve any difficult problems.

PMID- 16895778
TI  - Revision stapedectomy.
AB  - Revision stapedectomy can be a technically demanding operation. The surgeon must
      be prepared for many pathologic conditions before revision stapes surgery.
      Appropriate preoperative patient counseling is a must. The best chance for
      hearing improvement is in those cases that have a delayed conductive hearing loss
      after primary stapedectomy. This article serves as a guideline for discussing the
      myriad possibilities that may be encountered during this type of revision
      stapedectomy. Indications for revision stapedectomy and general surgical
      guidelines for management of specific pathologic conditions are discussed. The
      material presented is based on literature review, the authors' personal
      experience, and a review of temporal bone studies relative to stapes surgery.

PMID- 16895779
TI  - Revision ossiculoplasty.
AB  - Although ossiculoplasty, also known as ossicular chain reconstruction (OCR), was
      attempted initially in the early 1900s, it was not until the 1950s that it became
      commonplace and relatively well understood. Since then, there have been numerous
      technologic advances and a gain in the understanding of ossiculoplasty. However,
      successful OCR with resulting long-term stability can be a daunting task.
      Typically, the most common condition requiring revision OCR is chronic
      suppurative otitis media (COM) with or without cholesteatoma. Primary and
      revision OCR are performed also for blunt and penetrating trauma-induced
      conductive hearing loss, congenital defects (eg, atresia), and benign and
      malignant tumors. Typically, reconstruction in ears with COM is more difficult
      than in ears without infection. This article discusses the key factors involved
      in successful revision OCR.

PMID- 16895780
TI  - Endolymphatic sac revision for recurrent intractable Meniere's disease.
AB  - Meniere's disease can be observed uniquely in revisions of the conservative
      surgical procedure for endolymphatic sac enhancement, which preserves the
      labyrinth, unlike destructive procedures. Genetic anatomic abnormalities in
      patients lead to malabsorption of endolymph and symptoms of Meniere's that are
      reversed by endolymphatic sac enhancement, but disabling symptoms eventually may
      recur in a few cases and require revisional surgery. We observe developing
      pathophysiologic conditions intraoperatively and have modified our techniques to
      accommodate the redeveloped pathogenesis we observe and avoid complications found
      with earlier techniques. This conservative treatment allows patients (many of
      whom may develop bilateral Meniere's) to retain capacity to accept cochlear
      implants should they become advisable later.

PMID- 16895781
TI  - Revision mastoidectomy.
AB  - The first three priorities in surgery for chronic otitis media are (1) the
      elimination of progressive disease to produce a safe and dry ear, (2)
      modification of the anatomy of the tympanomastoid compartment to prevent
      recurrent disease, and (3) reconstruction of the hearing mechanism. The
      indications for revision following mastoidectomy for chronic otitis media thus
      involve failure to achieve any of these goals, including recurrent cholesteatoma,
      recurrent suppuration, recurrent perforation, or recurrent or residual conductive
      hearing loss. The focus of this article is the management of recurrent
      cholesteatoma or suppuration; that is, failure to achieve either of the first two
      priorities.

PMID- 16895782
TI  - Revision surgery for vertigo.
AB  - When confronted with vertigo after an otologic procedure, a surgeon first must
      identify the functional status of the inner ear by performing auditory and
      vestibular testing. Using this information in conjunction with knowledge of the
      primary disease process for which the initial procedure was performed, the
      surgeon can make a rational selection of the procedure required to eliminate
      vertigo. This article outlines a systematic approach to the selection of the
      appropriate revision procedure and discusses the specific advantages and
      disadvantages of these procedures used to control vertigo.

PMID- 16895783
TI  - Acoustic neuroma (vestibular schwannoma) revision.
AB  - The authors present their experience of more than 25 years, now in excess of 1200
      patients, with cerebellopontine angle tumors. This article focuses on the
      management of planned subtotal resection of acoustic tumors in five subjects, and
      unexpected "residual" discovered by MRI scanning in 10 cases, which represents,
      to the best of the authors' knowledge, a residual rate of 1% of operated
      patients. The rate of residual tumor is as high as 19% in some series and, in
      part, depends on the surgical approach. For the purpose of this article, the
      authors did not include their cases of neurofibromatosis, because these tumors
      behave differently than unilateral sporadic schwannomas.

PMID- 16895784
TI  - Revision glomus tumor surgery.
AB  - The infratemporal fossa approach type A is the best way to deal with recurrent
      tympano-jugular paragangliomas because facial nerve rerouting is fundamental to
      reaching the area of the internal carotid artery, where recurrence is likely to
      occur. Preservation of lower cranial nerve function is not feasible when there is
      tumor infiltration of the medial wall of the jugular bulb; any attempt at nerve
      dissection increases the risk of leaving some tumor remnants. Correct management
      of the internal carotid artery, including preoperative stent insertion or
      permanent preoperative balloon occlusion, is usually a fundamental step when
      dealing with these highly vascularized lesions. Because of the tumor tendency to
      infiltrate the bony structures, aggressive drilling of the temporal bone is also
      advised, especially at the level of the petrous apex. Patients affected by
      uncontrolled recurrences still die of this disease.

PMID- 16895786
TI  - Revision BAHA Surgery.
AB  - The osseointegrated auditory implant (BAHA) is a system used for hearing
      rehabilitation through direct bone conduction. Although BAHA surgery is not
      difficult, the surgeon must observe meticulous technique to prevent
      complications. Indications for revision BAHA surgery can be divided into (1)
      failure of fixture osseointegration; (2) bone overgrowth; or (3) skin reaction or
      skin loss. This article discusses the conditions that might predispose a patient
      to require BAHA revision, and the steps, if any, that can be taken to prevent
      these complications. Specific surgical steps for revision of each of these three
      conditions are also addressed.

PMID- 16895785
TI  - The challenges of revision skull base surgery.
AB  - Because the skull base is an anatomically complex structure, skull base tumors
      can hide easily in the crevices that interconnect the intra- and extracranial
      spaces and intermingle with important neurovascular structures. Often, total
      surgical resection of these tumors is not possible, and even with postoperative
      adjuvant radiotherapy, some recurrences after treatment are inevitable. Early
      detection of recurrent skull base tumors requires clinical vigilance and periodic
      imaging studies. The management of recurrent skull base tumors presents many
      challenges beyond those associated with primary procedures. A multidisciplinary
      setting that includes modern microsurgery and stereotactic radiation therapy
      provides patients with optimal care.

PMID- 16895787
TI  - Revision facial nerve surgery.
AB  - Transection of the facial nerve can result from blunt or penetrating trauma to
      the face or temporal bone. It can also occur accidentally during surgery, or as a
      planned surgical procedure carried out in the interest of eradicating disease. If
      transection is recognized at surgery, direct anastomosis or cable grafting is the
      procedure of choice. This article presents two cases with neither clinical nor
      electrical evidence of recovery. The authors review current understanding of the
      changes that occur in the neuron, axon, and muscle after injury to the nerve and
      the underlying pathology that led to graft failure in these cases. They also
      evaluate surgical options and diagnostic test results that help in selecting
      appropriate surgical procedures.

PMID- 16895788
TI  - Revision cochlear implantation.
AB  - Reoperation on a patient with an indwelling cochlear implant is uncommon. When
      necessary, surgery is performed for explantation of an existing device with
      immediate or delayed reimplantation, or for scalp flap revision and receiver
      stimulator repositioning in the case of infection or device migration. Rarely,
      revision surgery is performed to reintroduce intracochlear electrodes that may
      have partly or entirely extruded from the cochlea or were placed inappropriately.
      Successful revision cochlear implant surgery requires attention to certain
      surgical principles. Good outcomes, asa measured by speech perception tests, are
      common, but are not guaranteed. This article outlines the indications for
      revision cochlear implant surgery, the recommended surgical principles, and
      published outcomes from reimplantation.

PMID- 16895789
TI  - Nitrite in nitric oxide biology: cause or consequence? A systems-based review.
AB  - All life requires nitrogen compounds. Nitrite is such a compound that is
      naturally occurring in nature and biology. Over the years, the pharmacological
      stance on nitrite has undergone a surprising metamorphosis, from a vilified
      substance that generates carcinogenic nitrosamines in the stomach to a life
      saving drug that liberates a protective agent (nitric oxide or NO) during hypoxic
      events. Nitrite has been investigated as a vasodilator in mammals for over 125
      years and is a known by-product of organic nitrate metabolism. There has been a
      recent rediscovery of some of the vasodilator actions of nitrite in physiology
      along with novel discoveries which render nitrite a fundamental molecule in
      biology. Until recently nitrite was thought to be an inert oxidative breakdown
      product of endogenous NO synthesis but the past few years have focused on the
      reduction of nitrite back to NO in the circulation as a possible mechanism for
      hypoxic vasodilatation. Nitrite has evolved into an endogenous signaling molecule
      and regulator of gene expression that may not only serve as a diagnostic marker
      but also find its role as a potential therapeutic agent of cardiovascular
      disease. These data therefore warrant a reevaluation on the fate and metabolism
      of nitrite in biological systems. This review serves to encompass the history and
      recent evolution of nitrite, the compartment-specific metabolism of nitrite and
      its role in plasma as a biomarker for disease, the role of nitrite as a potential
      regulator of NO homeostasis, and the future of nitrite-based research.

PMID- 16895791
TI  - Tumor necrosis factor-alpha down-regulates human Cu/Zn superoxide dismutase 1
      promoter via JNK/AP-1 signaling pathway.
AB  - Overexpression of Cu/Zn superoxide dismutase 1 (SOD1) in monocytes blocks
      reactive oxygen species-induced inhibition of cell growth and apoptosis and
      renders cells resistant to the toxic effect of tumor necrosis factor (TNF)-alpha,
      suggesting that TNF-alpha represses the SOD1 gene in these cells. We herein show
      that TNF-alpha decreases SOD1 mRNA, protein, and promoter activity in U937 cells.
      Electrophoretic mobility-shift assays (EMSA) show that TNF-alpha decreased
      binding of three different complexes. Ectopic Sp1 overexpression markedly
      increased SOD1-basal promoter activity and partially antagonized the TNF-alpha
      inhibitory effect. In contrast, ectopic c-Jun overexpression mimics TNF-alpha
      inhibitory effects and antagonizes Sp1 stimulatory effects. In agreement with
      these findings, EMSA shows a TNF-alpha-induced increase in AP-1 and a decrease in
      Sp1 DNA binding. Disruption of the C/EBP site decreases, whereas mutation in the
      Sp1/Egr-1 site completely abolishes DNA-binding and promoter activity. A JNK
      inhibitor antagonized the negative effects of TNF-alpha on SOD1 promoter
      activity, suggesting that JNK signaling through c-Jun protein activation is
      critical for the TNF-alpha-dependent SOD1 repression. A greater understanding of
      the mechanisms of TNF-alpha-induced SOD1 repression could facilitate the design
      and development of novel therapeutic drugs for inflammatory conditions.

PMID- 16895790
TI  - Mechanism by which avenanthramide-c, a polyphenol of oats, blocks cell cycle
      progression in vascular smooth muscle cells.
AB  - Previously, we reported that avenanthramide-c (Avn-c), one of the major
      avenanthramides, polyphenols of oats, inhibited the serum-induced proliferation
      of vascular smooth muscle cells (SMC), which is an important process in the
      initiation and development of atherosclerosis. In the present study, we further
      investigated its cell cycle inhibitory mechanism. Rat embryonic aortic smooth
      muscle cell line A10 was used in this study. Flow cytometry analysis revealed
      that treatment of A10 cells with 80 muM Avn-c arrested the cell cycle in G1 phase
      as indicated by an increase in the number of cells in G1 phase and a decrease in
      the number of cells in S phase. This cell cycle arrest was associated with a
      decrease in the phosphorylation of retinoblastoma protein (pRb), whose
      hyperphosphorylation is a hallmark of the G1 to S transition in the cell cycle.
      The inhibition of pRb phosphorylation with Avn-c was accompanied by a decrease in
      cyclin D1 expression and an increase in cyclin-dependent kinase inhibitor p21cip1
      expression, without significant changes in p27kip1 expression. Furthermore, Avn-c
      treatment increased the expression level and stability of p53 protein, which
      could account for the increase of p21cip1 expression. Our results demonstrate for
      the first time that Avn-c, which is a unique polyphenol found in oats, arrests
      SMC proliferation at G1 phase by upregulating the p53-p21cip1 pathway and
      inhibiting pRB phosphorylation. This inhibitory effect of Avn-c on SMC
      proliferation is an additional indication for the potential health benefit of oat
      consumption in the prevention of coronary heart disease beyond its known effect
      through lowering blood cholesterol.

PMID- 16895792
TI  - Protective effect of vitamin E supplements on experimental atherosclerosis is
      modest and depends on preexisting vitamin E deficiency.
AB  - Vitamin E has failed to protect humans from cardiovascular disease outcome, yet
      its role in experimental atherosclerosis remains less clear. A previous study
      (Proc. Natl. Acad. Sci. USA 97:13830-13834; 2000) showed that vitamin E
      deficiency caused by disruption of the alpha-tocopherol transfer protein gene
      (Ttpa) is associated with a modest increase in atherosclerosis in apolipoprotein
      E gene deficient (Apoe(-/-)) mice. Here we confirm this finding and report that
      in Apoe(-/-)Ttpa(-/-) mice dietary alpha-tocopherol (alphaT) supplements restored
      circulating and aortic levels of alphaT, and decreased atherosclerosis in the
      aortic root to a level comparable to that seen in Apoe(-/-) mice. However, such
      dietary supplements did not decrease disease in Apoe(-/-) mice, whereas dietary
      supplements with a synthetic vitamin E analog (BO-653), either alone or in
      combination with alphaT, decreased atherosclerosis in Apoe(-/-) and in Apoe(-/
      )Ttpa(-/-) mice. Differences in atherosclerosis were not associated with changes
      in the arterial concentrations of F(2)-isoprostanes and cholesterylester
      hydro(pero)xides, nor were they reflected in the resistance of plasma lipids to
      ex vivo oxidation. These results show that vitamin E at best has a modest effect
      on experimental atherosclerosis in hyperlipidemic mice, and only in situations of
      severe vitamin E deficiency and independent of lipid oxidation in the vessel
      wall.

PMID- 16895793
TI  - Dietary soy modulates endothelium-dependent relaxation in aged male rats:
      Increased agonist-induced endothelium-derived hyperpolarising factor and basal
      nitric oxide activity.
AB  - We examined the effects of dietary soy on the contributions of endothelium
      derived hyperpolarising factor (EDHF), nitric oxide (NO), and oxidative stress to
      vascular tone in isolated aortic rings and small mesenteric and pulmonary
      arteries in vitro. Male Wistar rats were either continuously fed a soy-deficient
      diet (SD) or switched from a soy-deficient diet to a soy-rich one for 6 months
      (SW). Contractile responses were generally smaller in arteries from SW rats. In
      mesenteric arteries, this difference was blunted by L-NAME, but not by
      charybdotoxin and apamin. Preconstricted SW mesenteric arteries were more
      sensitive to acetylcholine (ACh) than SD ones. This difference was unaffected by
      L-NAME but was abolished by charybdotoxin and apamin. Exogenous superoxide
      dismutase (SOD) and catalase induced powerful relaxations in aortic rings, which
      were smaller in those from SW rats. In mesenteric and pulmonary arteries,
      however, they partially inhibited ACh-mediated relaxation, and enhanced
      PGF(2alpha)-mediated contraction, respectively. Our results suggest that feeding
      aging male rats a soy-rich diet results in improved agonist-mediated EDHF
      production and a generalized reduction in contractile force, which is partly due
      to elevated basal NO. Our data also suggest a prorelaxant role for endogenous
      H(2)O(2) in small arteries, which is modulated by a soy diet.

PMID- 16895794
TI  - Total nitrogen oxide following exercise testing reflects endothelial function and
      discriminates health status.
AB  - Nitric oxide (NO) bioavailability is important in vascular health, but unsuitable
      as a clinical measure due to biological oxidation. Total nitrogen oxides (NO(x))
      are stable but background nitrate levels make it difficult to detect disease
      based variation. We investigated the clinical discriminatory value of NO(x) as it
      relates to exercise capability (VO(2peak)) and brachial artery reactivity (BAR,
      an NO-dependent measure of endothelial health), in healthy (H), increased risk
      (RF), and known cardiovascular disease (CVD) subjects. BAR was measured using
      forearm occlusion/hyperemia stimulus. Subjects performed a maximal graded
      exercise test (GXT). Blood at rest, exercise termination, and 10 min into
      recovery was mixed equally with 0.1 M NaOH at 4 degrees C, filtered, and stored
      at -70 degrees C. NO(x) was measured by chemiluminescence. Seven of the RF group
      then exercise-trained for 6 months prior to retesting. The H group (n = 12) was
      younger, had higher VO(2peak), HDL levels, and baseline NO(x) values than the RF
      (n = 15) and CVD (n = 10) groups. NO(x) increased from baseline to recovery in
      the H group only (75.85 +/- 19.04 microM vs 97.76 +/- 31.93 microM; P <or= 0.01).
      BAR was greater in the H versus CVD group (7.24 +/- 3.78% vs 2.59 +/- 3.53%; P
      <or= 0.01). The relation between VO(2peak) and NO(x) recovery was significant
      across groups (r = 0.71, P <or= 0.01). Following training the RF subjects (n = 7)
      increased VO(2peak) (29.98 +/- 6.74 to 33.08 +/- 5.57 ml kg(-1) min(-1); P <or=
      0.05), BAR (3.19 +/- 3.96 to 6.86 +/- 4.81%; P <or= 0.05), and recovery NO(x)
      (18.29 +/- 6.46 to 66.48 + 21.11 microM; P <or= 0.01). These findings suggest
      that plasma NO(x) following GXT discriminate cardiovascular disease status, are
      related to regional endothelial function, and respond favorably to exercise
      training.

PMID- 16895795
TI  - Mechanism for manganese enhancement of dopamine-induced oxidative DNA damage and
      neuronal cell death.
AB  - Although the cause of dopaminergic cell death in Parkinson's disease is still
      poorly understood, there is accumulating evidence suggesting that metal ions can
      be involved in the processes. We investigated the effect of manganese on cell
      death and DNA damage in PC12 cells treated with dopamine. Mn(II) enhanced cell
      death induced by dopamine. Mn(II) also increased the 8-oxo-7,8-dihydro-2'
      deoxyguanosine (8-oxodG) contents of DNA in PC12 cells treated with dopamine. To
      clarify the mechanism of cellular DNA damage, we investigated DNA damage induced
      by dopamine and Mn(II) using (32)P-labeled DNA fragments. Mn(II) enhanced Cu(II)
      dependent DNA damage by dopamine. The Mn(II)-enhanced DNA damage was greatly
      increased by NADH. Piperidine and formamidopyrimidine-DNA glycosylase treatment
      induced cleavage sites mainly at T and G of the 5'-TG-3' sequence, respectively.
      Bathocuproine, a Cu(I) chelator, and catalase inhibited the DNA damage. Oxygen
      consumption and UV-visible spectroscopic measurements showed that Mn(II) enhanced
      autoxidation of dopamine with H(2)O(2) formation. These results suggest that
      reactive species derived from the reaction of H(2)O(2) with Cu(I) participates in
      Mn(II)-enhanced DNA damage by dopamine plus Cu(II). Therefore, it is concluded
      that oxidative DNA damage induced by dopamine in the presence of Mn(II), NADH,
      and Cu(II) is possibly linked to the degeneration of dopaminergic neurons.

PMID- 16895797
TI  - Comparative toxicities of putative phagocyte-generated oxidizing radicals toward
      a bacterium (Escherichia coli) and a yeast (Saccharomyces cerevisiae).
AB  - Toxicities of the radiolytically generated oxidizing radicals HO(*), CO(3)(-)(*),
      and NO(2)(*) toward suspension cultures of a bacterium (Escherichia coli) and a
      yeast (Saccharomyces cerevisiae) were examined. As demonstrated by the absence of
      protection from the membrane-impermeable HO(*) scavenger polyethylene glycol
      (PEG), externally generated HO(*) was not bactericidal under these conditions;
      however, partial protection by PEG was observed for S. cerevisiae, indicating the
      presence of a fungicidal pathway involving external HO(*). For both organisms,
      conversion of external HO(*) to the secondary radical, CO(3)(-)(*), by reaction
      with HCO(3)(-) increases their susceptibility to radiolytic killing. In contrast,
      externally generated NO(2)(*) exhibited toxicity comparable to that of CO(3)(
      )(*) toward E. coli, but completely blocked the extracellular toxicity of HO(*)
      toward S. cerevisiae. Cogeneration of equal fluxes of NO(2)(-)(*) and either
      HO(*) or CO(3)(-)(*) also essentially eliminated the extracellular microbicidal
      reactions. This behavior is consistent with expectations based upon relative
      rates of radical-radical self-coupling and cross-coupling reactions. The
      different patterns of toxicity observed imply fundamentally different
      microbicidal mechanisms for the two organisms, wherein the bacterium is
      susceptible to killing by oxidation of highly reactive targets on its cellular
      envelope but, despite undergoing similar oxidative insult, the fungus is not.

PMID- 16895796
TI  - Effects of ectopic expression of Drosophila DNA glycosylases dOgg1 and RpS3 in
      mitochondria.
AB  - The main purpose of this study was to determine whether enhancement of repair
      capacity would attenuate mitochondrial DNA oxidative damage and result in greater
      cell survival under stressful conditions. The repair of oxidative damage is
      initiated by DNA glycosylases, which catalyze the excision of oxidized bases,
      such as 8-hydroxydeoxyguanosine (8-oxodG). Drosophila DNA glycosylases, dOgg1 and
      RpS3, were ectopically expressed within the mitochondrial matrix in Drosophila S2
      cells, causing a severalfold decrease in the levels of 8-oxodG in mitochondrial
      DNA. Unexpectedly, cells did not show increased resistance to oxidative stress,
      but instead became more susceptible to treatment with hydrogen peroxide or
      paraquat. Even in the absence of oxidative challenge, cells expressing RpS3 or
      dOgg1 in mitochondria exhibited increased apoptosis relative to controls, as
      determined by flow-cytometric analysis of Annexin V and DNA degradation measured
      by the Comet assay. Another notable finding was that ectopic expression of either
      dOgg1 or RpS3 in mitochondria increased cell survival after exposure to the
      nitric oxide donor SNAP. These results suggest that ectopic expression of one of
      the constituents of the DNA repair system in mitochondria may cause a
      perturbation in the base excision repair pathway and lower, rather than enhance,
      survivability.

PMID- 16895798
TI  - Molecular mechanism of glutathione-mediated protection from oxidized low-density
      lipoprotein-induced cell injury in human macrophages: role of glutathione
      reductase and glutaredoxin.
AB  - Macrophage death is a hallmark of advanced atherosclerotic plaque, and oxidized
      low-density lipoprotein (OxLDL) found in these lesions is believed to contribute
      to macrophage injury. However, the underlying mechanisms of this phenomenon are
      only poorly understood. Here we show that in human monocyte-derived macrophages,
      OxLDL depleted intracellular glutathione (GSH) and inhibited glutathione
      reductase, resulting in a marked diminution of the glutathione/glutathione
      disulfide ratio. In the absence of OxLDL, an 80% depletion of intracellular GSH
      levels did not affect cell viability, but glutathione depletion dramatically
      increased OxLDL-induced cell death. Conversely, supplementation of intracellular
      GSH stores with glutathione diethyl ester substantially diminished OxLDL
      toxicity. OxLDL also promoted protein-S-glutathionylation, which was increased in
      macrophages pretreated with the glutathione reductase inhibitor BCNU. Knockdown
      experiments with siRNA directed against glutathione reductase and glutaredoxin
      showed that both enzymes are essential for the protection of macrophages against
      OxLDL. Finally, the peroxyl-radical scavenger Trolox did not prevent GSH
      depletion but completely blocked OxLDL-induced protein-S-glutathionylation and
      cell death. These data suggest that OxLDL promotes ROS formation and protein-S
      glutathionylation by a mechanism independent from its effect on GSH depletion.
      Neither mechanism was sufficient to induce macrophage injury, but when stimulated
      concurrently, these pathways promoted the accumulation of protein-glutathione
      mixed disulfides and cell death.

PMID- 16895799
TI  - Differential effects of oxidized LDL on apolipoprotein AI and B synthesis in
      HepG2 cells.
AB  - Oxidized low-density lipoproteins (Ox-LDL) are key elements in atherogenesis.
      Apolipoprotein AI (apoAI) is an active component of the antiatherogenic high
      density lipoproteins (HDL). In contrast, plasma apolipoprotein B (apoB), the main
      component of LDL, is highly correlated with coronary risk. Our results, obtained
      in HepG2 cells, show that Ox-LDL, unlike native LDL, leads to opposite effects on
      apoB and apoAI, namely a decrease in apoAI and an increase in apoB secretion as
      evaluated by [(3)H]leucine incorporation and specific immunoprecipitation.
      Parallel pulse-chase studies show that Ox-LDL impaired apoB degradation, whereas
      apoAI degradation was increased and mRNA levels were decreased. We also found
      that enhanced lipid biosynthesis of both triglycerides and cholesterol esters was
      involved in the Ox-LDL-induced increase in apoB secretion. Our data suggest that
      the increase in apoB and decrease in apoAI secretion may in part contribute to
      the known atherogenicity of Ox-LDL through an elevated LDL/HDL ratio, a strong
      predictor of coronary risk in patients.

PMID- 16895800
TI  - Aging, sex differences, and oxidative stress in human respiratory and limb
      muscles.
AB  - Oxidative stress is involved in the sarcopenia of aging muscles. On the grounds
      that ventilatory muscles are permanently active, and their activity may even
      increase with aging, we hypothesized that the levels of oxidative stress would
      probably be increased in the external intercostals of elderly healthy
      individuals. We conducted a case-control study in which reactive carbonyl groups,
      malondialdehyde-protein adducts, 3-nitrotyrosine immunoreactivity, Mn-superoxide
      dismutase (Mn-SOD), and catalase were detected using immunoblotting in external
      intercostals and quadriceps (open muscle biopsies) obtained from 12 healthy
      elderly and 12 young individuals of both sexes. In elderly subjects, reactive
      carbonyls, malondialdehyde-protein adducts, 3-nitrotyrosine, Mn-SOD, and catalase
      were significantly greater in the external intercostals than in the young
      controls. A post hoc analysis, in which men and women from both groups were
      analyzed separately, revealed that the external intercostals of elderly women,
      but not those of elderly men, showed significantly increased levels of reactive
      carbonyls, malondialdehyde-protein adducts, 3-nitrotyrosine, and Mn-SOD compared
      to those of control females. This study suggests that differences in muscle
      activity might explain the differential pattern of oxidative stress observed in
      human respiratory and limb muscles with aging as well as the likely existence of
      a sex-related regulation of this phenomenon in these muscles.

PMID- 16895802
TI  - Oxidant stress and skeletal muscle glucose transport: roles of insulin signaling
      and p38 MAPK.
AB  - Oxidative stress can impact the regulation of glucose transport activity in a
      variety of cell lines. In the present study, we assessed the direct effects of an
      oxidant stress on the glucose transport system in intact mammalian skeletal
      muscle preparations. Type IIb (epitrochlearis) and type I (soleus) muscles from
      insulin-sensitive lean Zucker rats were incubated in 8 mM glucose for 2 h in the
      absence or presence of 100 mU/ml glucose oxidase to produce the oxidant hydrogen
      peroxide (H(2)O(2)) (60-90 microM). Glucose transport, glycogen synthase
      activity, and metabolic signaling factors were then assessed. H(2)O(2)
      significantly (p < 0.05) activated basal glucose transport and glycogen synthase
      activities and increased insulin receptor tyrosine phosphorylation, insulin
      receptor substrate-1 associated with the p85 subunit of phosphatidylinositol-3'
      kinase (PI3-kinase), and Ser(473) phosphorylation of Akt in both muscle types.
      This induction of glucose transport by the oxidant stress was prevented by the
      PI3-kinase inhibitor wortmannin. The oxidant stress also significantly increased
      phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK) and 5'-AMP
      dependent protein kinase. Interestingly, selective inhibition of p38 MAPK using
      A304000 substantially reduced the activation of glucose transport induced by the
      oxidant stress. These results support a direct role for oxidative stress in the
      activation of the glucose transport system in mammalian skeletal muscle and
      indicate that this process involves engagement of and possible interactions
      between the PI3-kinase-dependent signaling pathway and activation of p38 MAPK.

PMID- 16895801
TI  - Early determinants of H2O2-induced endothelial dysfunction.
AB  - Reactive oxygen species (ROS) can stimulate nitric oxide (NO(*)) production from
      the endothelium by transient activation of endothelial nitric oxide synthase
      (eNOS). With continued or repeated exposure, NO(*) production is reduced,
      however. We investigated the early determinants of this decrease in NO(*)
      production. Following an initial H(2)O(2) exposure, endothelial cells responded
      by increasing NO(*) production measured electrochemically. NO(*) concentrations
      peaked by 10 min with a slow reduction over 30 min. The decrease in NO(*) at 30
      min was associated with a 2.7-fold increase in O(2)(*-) production (p < 0.05) and
      a 14-fold reduction of the eNOS cofactor, tetrahydrobiopterin (BH(4), p < 0.05).
      Used as a probe for endothelial dysfunction, the integrated NO(*) production over
      30 min upon repeated H(2)O(2) exposure was attenuated by 2.1-fold (p = 0.03).
      Endothelial dysfunction could be prevented by BH(4) cofactor supplementation, by
      scavenging O(2)(*-) or peroxynitrite (ONOO(-)), or by inhibiting the NADPH
      oxidase. Hydroxyl radical (()OH) scavenging did not have an effect. In summary,
      early H(2)O(2)-induced endothelial dysfunction was associated with a decreased
      BH(4) level and increased O(2)(*-) production. Dysfunction required O(2)(*-),
      ONOO(-), or a functional NADPH oxidase. Repeated activation of the NADPH oxidase
      by ROS may act as a feed forward system to promote endothelial dysfunction.

PMID- 16895803
TI  - Relative importance of cellular uptake and reactive oxygen species for the
      toxicity of alloxan and dialuric acid to insulin-producing cells.
AB  - The diabetogenic agent alloxan is selectively accumulated in insulin-producing
      cells through uptake via the GLUT2 glucose transporter in the plasma membrane. In
      the presence of intracellular thiols, especially glutathione, alloxan generates
      "reactive oxygen species" (ROS) in a cyclic reaction between this substance and
      its reduction product, dialuric acid. The cytotoxic action of alloxan is
      initiated by free radicals formed in this redox reaction. Autoxidation of
      dialuric acid generates superoxide radicals (O(2)(*-)) and hydrogen peroxide
      (H(2)O(2)), and finally hydroxyl radicals ((*)OH). Thus, while superoxide
      dismutase (SOD) only reduced the toxicity, catalase, in particular in the
      presence of SOD, provided complete protection of insulin-producing cells against
      the cytotoxic action of alloxan and dialuric acid due to H(2)O(2) destruction and
      the prevention of hydroxyl radical ((*)OH) formation, indicating that it is the
      hydroxyl radical ((*)OH) which is the ROS ultimately responsible for cell death.
      After selective accumulation in pancreatic beta cells, which are weakly protected
      against oxidative stress, the cytotoxic glucose analogue alloxan destroys these
      insulin-producing cells and causes a state of insulin-dependent diabetes mellitus
      through ROS-mediated toxicity in rodents and in other animal species, which
      express this glucose transporter isoform in their beta cells.

PMID- 16895804
TI  - A novel SOD-mimetic permeability transition inhibitor agent protects ischemic
      heart by inhibiting both apoptotic and necrotic cell death.
AB  - In ischemia-reperfusion injuries, elevated calcium and reactive oxygen species
      (ROS) induce mitochondrial permeability transition (mPT), which plays a pivotal
      role in mediating damages and cell death. Inhibition of mPT decreases necrotic
      cell death; however, during reperfusion, the continuous production of ROS may
      contribute to the temporary opening of the pore and thus the onset of the delayed
      apoptotic cell death. Based on amiodarone structure, we developed the first SOD
      mimetic mPT inhibitor (HO-3538) that can eliminate ROS in the microenvironment of
      the permeability pore. In isolated mitochondria, HO-3538 inhibited mPT and the
      release of proapoptotic mitochondrial proteins. It had a ROS scavenging effect
      and antiapoptotic effect in a cardiomyocyte line and it diminished release of
      mitochondrial proapoptotic proteins. Furthermore, HO-3538 significantly enhanced
      the recovery of mitochondrial energy metabolism and functional cardiac
      parameters; decreased infarct size, lipid peroxidation, and protein oxidation;
      and suppressed necrotic as well as apoptotic cell death pathways in Langendorff
      perfused hearts. In these respects it was somewhat superior to its two
      constituents, amiodarone and a pyrrol-derivative free radical scavenger. These
      data suggest that the SOD-mimetic mPT inhibitors are ideal candidates for drug
      development for the alleviation of postinfarct myocardial injuries.

PMID- 16895805
TI  - Multiple attacks from multiple perspectives.

PMID- 16895807
TI  - Placebo surgery research: a blinding imperative.
AB  - In placebo surgery research, intervention group subjects receive a real surgical
      procedure, and control subjects receive a sham surgical procedure. The sham
      procedure is designed to recapitulate enough of the real procedure to blind
      participants to group assignment. Placebo surgery designs are used to control for
      placebo effects, and to eliminate the bias that might result if participants and
      investigators were aware of group assignment when outcomes are measured. In
      placebo surgery studies, in which participants are placed at increased risk to
      achieve the scientific validity provided by blinding, it is imperative that the
      blind be maintained, and maintainable, to justify putting subjects at risk to
      achieve it. In circumstances in which the outcome assessors are not fully
      blinded, or in which the intervention is not amenable to rigorous blinding,
      placebo surgery studies are not ethical. Investigators doing placebo surgery
      trials should obtain data on the integrity of the blind from both subjects and
      outcome assessors, to inform the validity of the results and to provide input for
      "blindability" decisions involving future trials.

PMID- 16895808
TI  - Forming research questions.

PMID- 16895809
TI  - Finding information about the burden of disease.

PMID- 16895810
TI  - Preparing a research protocol to improve chances for success.

PMID- 16895811
TI  - Preparing reports for publication and responding to reviewers' comments.

PMID- 16895812
TI  - Dealing with the media.

PMID- 16895813
TI  - Clinical heterogeneity was a common problem in Cochrane reviews of physiotherapy
      and occupational therapy.
AB  - BACKGROUND AND OBJECTIVE: To identify the strategies used to deal with the
      clinical heterogeneity of interventions and multiple outcome measures used in
      Cochrane reviews on physiotherapy and occupational therapy. METHODS: A search for
      systematic reviews on physiotherapy and occupational therapy in the Cochrane
      Library was performed. Data on the method of categorization of interventions, on
      measures, and on the method of data synthesis were systematically extracted.
      RESULTS: 52 reviews were identified. In 22 (42%) reviews only one index
      intervention was evaluated, in the other 30 reviews index interventions were
      categorized. A large diversity in the number and type of outcome measures was
      found (median 6.5, range 1-23). In 48% of the reviews one or more primary outcome
      measures were defined. In 52% of the reviews no quantitative data synthesis was
      performed, whereas five different methods for qualitative data synthesis were
      applied in 11 reviews. CONCLUSIONS: Limitation to a few outcome measures and
      explicit procedures for the categorization of interventions might increase the
      transparency and reproducibility of systematic reviews on physiotherapy and
      occupational therapy. Qualitative data synthesis is not often applied, although
      it is a useful tool to summarize results if a quantitative synthesis is not
      appropriate. International consensus on a method for qualitative synthesis is
      clearly needed.

PMID- 16895814
TI  - ANCOVA versus change from baseline: more power in randomized studies, more bias
      in nonrandomized studies [corrected].
AB  - BACKGROUND AND OBJECTIVE: For inferring a treatment effect from the difference
      between a treated and untreated group on a quantitative outcome measured before
      and after treatment, current methods are analysis of covariance (ANCOVA) of the
      outcome with the baseline as covariate, and analysis of variance (ANOVA) of
      change from baseline. This article compares both methods on power and bias, for
      randomized and nonrandomized studies. METHODS: The methods are compared by
      writing both as a regression model and as a repeated measures model, and are
      applied to a nonrandomized study of preventing depression. RESULTS: In randomized
      studies both methods are unbiased, but ANCOVA has more power. If treatment
      assignment is based on the baseline, only ANCOVA is unbiased. In nonrandomized
      studies with preexisting groups differing at baseline, the two methods cannot
      both be unbiased, and may contradict each other. In the study of depression,
      ANCOVA suggests absence, but ANOVA of change suggests presence, of a treatment
      effect. The methods differ because ANCOVA assumes absence of a baseline
      difference. CONCLUSION: In randomized studies and studies with treatment
      assignment depending on the baseline, ANCOVA must be used. In nonrandomized
      studies of preexisting groups, ANOVA of change seems less biased than ANCOVA, but
      two control groups and two baseline measurements are recommended.

PMID- 16895815
TI  - Interrater reliability of measurements of comorbid illness should be reported.
AB  - OBJECTIVE: Comorbidity indices are commonly used to stratify patients to control
      for treatment selection bias. The objectives here were to review the reporting of
      interrater reliability when studies use comorbidity indices in clinical research
      publications and to report the interrater reliability of four common indices in a
      particular research setting. STUDY DESIGN AND SETTING: Four trained abstractors
      reviewed the same 40 charts of patients with squamous cell carcinoma of the head
      and neck from a regional cancer center. Scores for the Charlson Index, the Index
      of Co-existent Disease, the Cumulative Illness Rating Scale, and the Kaplan
      Feinstein Classification were calculated, and the intraclass correlation
      coefficient was used to assess interrater reliability. RESULTS: The details on
      the training of abstractors and the results of interrater reliability tests are
      not commonly reported. In our study setting, the Charlson Index had excellent
      reliability and the others had acceptable reliability. CONCLUSION: If the quality
      of a study using an index or scale is to be assessed, the reliability and
      interrater reliability of the score assignment process should be reported.

PMID- 16895816
TI  - In an exploratory prospective study on multimorbidity general and disease-related
      susceptibility could be distinguished.
AB  - OBJECTIVES: To further disentangle multimorbidity and its relation with
      psychosocial characteristics, by categorizing combinations of diseases within a
      patient as general or disease-related susceptibility, based on the presence or
      absence of a pathophysiological communality of diseases. STUDY DESIGN AND
      SETTING: A cohort of 3,460 patients that previously took part in a study on
      multimorbidity was followed up for a period of 2 years. CONTEXT: the Registration
      Network Family Practices, which is a continuous and computerized database in
      Dutch general practice that covered over 60,000 patients at the time of the
      study. RESULTS: During 2-year follow-up 91.6% did not show susceptibility, 4.2%
      showed general susceptibility, 1.4% disease-related susceptibility, 0.8% both
      general and disease-related susceptibility, and 1.9% patients could not be
      classified. None of the studied characteristics was significantly related to the
      occurrence of disease-related susceptibility. A decreased risk for general
      disease susceptibility related to an internal health locus of control, an active
      and palliative coping style, and the occurrence of positive life events.
      CONCLUSION: The distinction between general susceptibility and disease-related
      susceptibility is feasible and seems useful. Further development of this
      methodology is needed, as is confirmation of these results in a larger study
      population.

PMID- 16895818
TI  - Simulated computerized adaptive test for patients with lumbar spine impairments
      was efficient and produced valid measures of function.
AB  - OBJECTIVE: To equate physical functioning (PF) items with Back Pain Functional
      Scale (BPFS) items, develop a computerized adaptive test (CAT) designed to assess
      lumbar spine functional status (LFS) in people with lumbar spine impairments, and
      compare discriminant validity of LFS measures (theta(IRT)) generated using all
      items analyzed with a rating scale Item Response Theory model (RSM) and measures
      generated using the simulated CAT (theta(CAT)). METHODS: We performed a secondary
      analysis of retrospective intake rehabilitation data. RESULTS: Unidimensionality
      and local independence of 25 BPFS and PF items were supported. Differential item
      functioning was negligible for levels of symptom acuity, gender, age, and
      surgical history. The RSM fit the data well. A lumbar spine specific CAT was
      developed that was 72% more efficient than using all 25 items to estimate LFS
      measures. theta(IRT) and theta(CAT) measures did not discriminate patients by
      symptom acuity, age, or gender, but discriminated patients by surgical history in
      similar clinically logical ways. theta(CAT) measures were as precise as
      theta(IRT) measures. CONCLUSION: A body part specific simulated CAT developed
      from an LFS item bank was efficient and produced precise measures of LFS without
      eroding discriminant validity.

PMID- 16895817
TI  - Length of comorbidity lookback period affected regression model performance of
      administrative health data.
AB  - BACKGROUND AND OBJECTIVE: The impact of different comorbidity ascertainment
      lookback periods on modeling posthospitalization mortality and readmission was
      examined. METHODS: Index cases comprised medical (n = 326,456) and procedural (n
      = 349,686) patients with a hospital admission from 1990-1996. Administrative
      hospital data were extracted for 102 comorbidities, ascertained at index
      admission and for 1-, 2-, 3-, and 5-year lookback periods. Deaths and
      readmissions were identified within 12 months and 30 days of separation,
      respectively. Hierarchically nested and nonnested Cox regressions as well as
      Receiver Operator Characteristic Area Under the Curve (ROC-AUC) were used to
      determine model-fit and predictive ability of lookback period models. RESULTS:
      The 1-year lookback period provided the best model-fit for both patient groups
      when modeling mortality. A similar model-fit was seen at index admission for
      procedural but not medical patients. The superior readmission model employed 5
      years of lookback for both patient groups. With one exception, all lookback
      period models were superior to those abstracting comorbidity from index admission
      only. Similar results were evident from ROC-AUC, although greater predictive
      ability was seen with modeling of mortality (0.847-0.923) compared with
      readmission (0.593-0.681). CONCLUSION: The explanatory power of regression
      models, when adjusting for comorbidity, is influenced by length of lookback,
      outcome investigated and clinical subgroup. Shorter periods (approximately 1
      year) appear appropriate for modeling posthospitalization mortality, whereas
      longer lookback periods are superior for readmission outcomes.

PMID- 16895819
TI  - Automated medication error studies with audit supplementation were effectively
      designed and analyzed by time series.
AB  - BACKGROUND AND OBJECTIVE: To provide researchers with an efficient yet
      methodologically robust method to design and analyze studies of the effectiveness
      of quality improvement interventions targeted at medical errors. METHODS: An
      interrupted time-series design was chosen. Error rates of a preintervention
      observational period are compared to those of an intervention period (interrupted
      by a brief transitional period not used in the analysis). Potential errors are
      flagged by computerized analysis. The positive predictive value of this automated
      method is established by targeted expert review of random samples of monthly
      admissions with flagged errors. The lengths of the preintervention and
      intervention observational periods and number of audits per month are determined
      via power and type I error analysis. The setting was a future study of electronic
      alert systems for errors related to nephrotoxic agents in a medium-sized
      hospital. RESULTS: Based on these methods, a study was deemed feasible to be
      conducted over a 38-month period, auditing 40 potential errors per month.
      CONCLUSION: A logistic monthly error process model with independent variables (1)
      time in months (same slope pre vs. postintervention), and (2) a discrete jump
      postintervention to assess the effect size, offers a flexible, easy-to-interpret
      way to attack this problem.

PMID- 16895820
TI  - Testing multiple statistical hypotheses resulted in spurious associations: a
      study of astrological signs and health.
AB  - OBJECTIVES: To illustrate how multiple hypotheses testing can produce
      associations with no clinical plausibility. STUDY DESIGN AND SETTING: We
      conducted a study of all 10,674,945 residents of Ontario aged between 18 and 100
      years in 2000. Residents were randomly assigned to equally sized derivation and
      validation cohorts and classified according to their astrological sign. Using the
      derivation cohort, we searched through 223 of the most common diagnoses for
      hospitalization until we identified two for which subjects born under one
      astrological sign had a significantly higher probability of hospitalization
      compared to subjects born under the remaining signs combined (P<0.05). RESULTS:
      We tested these 24 associations in the independent validation cohort. Residents
      born under Leo had a higher probability of gastrointestinal hemorrhage
      (P=0.0447), while Sagittarians had a higher probability of humerus fracture
      (P=0.0123) compared to all other signs combined. After adjusting the significance
      level to account for multiple comparisons, none of the identified associations
      remained significant in either the derivation or validation cohort. CONCLUSIONS:
      Our analyses illustrate how the testing of multiple, non-prespecified hypotheses
      increases the likelihood of detecting implausible associations. Our findings have
      important implications for the analysis and interpretation of clinical studies.

PMID- 16895821
TI  - Predictors of mortality for lower respiratory infections in nursing home
      residents with dementia were validated transnationally.
AB  - BACKGROUND AND OBJECTIVE: Generalizability of clinical predictors for mortality
      from lower respiratory infection (LRI) in nursing home residents has not been
      assessed for residents with dementia. STUDY DESIGN AND SETTING: In prospective
      cohort studies of LRI in 61 nursing homes in the Netherlands (n = 541) and 36
      nursing homes in Missouri, USA (n = 564), we examined 14-day and 1- and 3-month
      mortality in residents with dementia who were treated with antibiotics. RESULTS:
      A logistic model predicting 14-day mortality derived from Dutch data included
      eating dependency, elevated pulse, decreased alertness, respiratory difficulty,
      insufficient fluid intake, high respiratory rate, male gender, and pressure
      sores. After adjusting coefficients with the heuristic shrinkage factor, the 14
      day model showed good discrimination and calibration in both datasets. The
      apparent c-statistic for the original Dutch model was 0.80 (after correction for
      optimism, it was 0.75); the c-statistic was 0.74 in the U.S. validation
      population. The models predicting 1- and 3-month mortality showed moderate
      performance. A scoring system for estimating 14-day mortality performed equally
      well as the original model. CONCLUSION: We identified a set of credible clinical
      predictors that are easily assessed and demonstrated validity in identifying
      residents at low risk of dying from LRI across different nursing home
      populations. This tool should inform decision-making for families and doctors.

PMID- 16895822
TI  - Publication bias affected the estimate of postoperative nausea in an acupoint
      stimulation systematic review.
AB  - BACKGROUND AND OBJECTIVE: To assess the effect of publication bias and country
      effect on the results and conclusion of a systematic review of wrist P6 acupoint
      stimulation for the prevention of postoperative nausea and vomiting. METHODS:
      Reanalysis of a systematic review of 26 randomized trials comparing P6 acupoint
      stimulation with sham published in the Cochrane Database of Systematic Reviews
      using the Copas' sensitivity approach. RESULTS: If it is assumed that all studies
      that have ever been carried out are included, or that those selected for review
      are truly representative of all such studies, then the estimated relative risk
      (RR) for nausea was 0.71 (95% CI: 0.58 to 0.88, P<.01) and for vomiting was 0.70
      (95% CI: 0.56 to 0.88, P<.01) after adjusting for country effect. For nausea,
      adjustment for publication bias suggests that the risk has been overestimated. If
      around 33% of studies have been unpublished, the RR of nausea (0.92, 95% CI: 0.80
      to 1.06, P=.25) is no longer significant. For vomiting, however, there is no
      strong evidence of publication bias. The number of unpublished studies required
      to substantially overturn the above significant result is implausibly large.
      CONCLUSION: Publication bias affects the published estimate of postoperative
      nausea, not vomiting.

PMID- 16895823
TI  - Patients undergoing knee surgery provided accurate ratings of preoperative
      quality of life and function 2 weeks after surgery.
AB  - OBJECTIVE: To evaluate patients' ability to recall their preoperative self
      reported quality of life, function, and general health 2 weeks postoperatively.
      STUDY DESIGN AND SETTING: We randomized consecutive patients undergoing
      arthroscopic knee surgery to group I (assessments at 4 weeks preoperatively, on
      the day of surgery, and 2 weeks and 12 months postoperatively) or group II
      (assessments at 2 weeks and 12 months postoperatively). At each visit patients
      completed disease-specific, knee-specific, and generic health rating scales. At a
      median of 2 weeks postoperative (range, 0.6 to 14 weeks), patients completed
      questionnaires according to their recollection of their health 2 weeks before
      surgery. RESULTS: Agreement between actual and recalled data was excellent for
      disease-specific (ICC(WOMET)=0.88 (95% CI 0.82-0.91), ICC(ACL-QOL)=0.86 (95% CI
      0.75-0.91)), knee-specific (ICC(IKDC)=0.92 (95% CI 0.90-0.94), ICC(KOOS)=0.93
      (95% CI 0.91 to 0.95), and general physical health (ICC(SF-36(PCS))=0.81 (95% CI
      0.75-0.86)) instruments. Agreement for general mental health was moderate (ICC(SF
      36(MCS))=0.67 (95% CI 0.58-0.75). Greater error associated with recalled ratings
      contributed to small increases in sample size requirements or small decreases in
      power to detect differences between groups. CONCLUSION: Patients recalled their
      preoperative quality of life, function, and general health at 2 weeks
      postoperative with sufficiently high accuracy to warrant substituting
      prospectively collected baseline data with recalled ratings.

PMID- 16895824
TI  - Validity of a food frequency questionnaire varied by age and body mass index.
AB  - BACKGROUND AND OBJECTIVE: The validity of food frequency questionnaires (FFQs) in
      measuring food consumption and nutrient intake has to be assessed. The objective
      of this study was to assess the validity of a 128-item FFQ in specific subgroups
      of Finnish adults. METHODS: The study included 294 subjects (137 men and 157
      women). A 3-day food record was used as the reference method. RESULTS: The mean
      intake of all nutrients except alcohol was higher measured with the FFQ than with
      the food records. In general, the Pearson correlations for energy adjusted
      nutrients between the FFQ and the food records were higher in women than in men.
      The correlations ranged from 0.14 (retinol) to 0.66 (fiber and alcohol) in men,
      and from 0.20 (long-chain n-3 fatty acids) to 0.70 (alcohol) in women. The
      results in subgroups showed that measuring nutrient intakes is more difficult
      among younger (30-50 years) women and overweight men and women than among others.
      CONCLUSIONS: The study showed that the FFQ is a useful tool in epidemiologic
      studies in measuring the diet of Finnish adults given that the problems among
      specific subgroups are taken into account in interpretation.

PMID- 16895825
TI  - Modeling predicted that tobacco control policies targeted at lower educated will
      reduce the differences in life expectancy.
AB  - BACKGROUND AND OBJECTIVE: To estimate the effects of reducing the prevalence of
      smoking in lower educated groups on educational differences in life expectancy.
      METHODS: A dynamic Markov-type multistate transition model estimated the effects
      on life expectancy of two scenarios. A "maximum scenario" where educational
      differences in prevalence of smoking disappear immediately, and a "policy target
      scenario" where difference in prevalence of smoking is halved over a 20-year
      period. The two scenarios were compared to a reference scenario, where smoking
      prevalences do not change. Five Dutch cohort studies, involving over 67,000
      participants aged 20 to 90 years, provided relative mortality risks by
      educational level, and smoking habits were assessed using national data of more
      than 120,000 persons. RESULTS: In the reference scenario, the difference in life
      expectancy at age 40 between highest and lowest educated groups was 5.1 years for
      men and 2.7 years for women. In the "maximum scenario" these differences were
      reduced to 3.6 years for men and 1.7 years for women (reduction approximately
      30%), and in the "policy target-scenario" differences were 4.7 years for men and
      2.4 years for women (reduction approximately 10%). CONCLUSION: Theoretically,
      educational differences in life expectancy would be reduced by 30% at maximum, if
      variations in smoking prevalence were eliminated completely. In practice, tobacco
      control policies that are targeted at the lower educated may reduce the
      differences in life expectancy by approximately 10%.

PMID- 16895826
TI  - French academic physicians had a poor knowledge of terms used in clinical
      epidemiology.
AB  - OBJECTIVES: To assess academic physicians' understanding and usage of basic
      epidemiological terms commonly used in medical journals. STUDY DESIGN AND
      SETTING: Observational study. A total of 274 physicians, working in a teaching
      hospital in Paris, France were asked to answer a questionnaire including four
      vignettes presenting the results of a therapeutic, a diagnostic, a prognostic
      study and a meta-analysis of clinical trials. RESULTS: A total of 130 (47%)
      questionnaires were returned. We observed the highest proportion of good answers
      for questions about absolute risk reduction (87.7%), sensitivity (84.6%), and
      specificity (80%); and the lowest for the calculation and use of the likelihood
      ratio (16.9% and 9.2%, respectively). The global mean score was 5.0/10 (95%
      confidence interval=4.6-5.4, range 0-9.4). Physicians got higher scores for
      questions related to treatment than for questions related to diagnosis: mean
      scores 7.1 (6.6-7.6) vs. 4.2 (3.8-4.6). Regression analysis did not reveal any
      significant relationship between global performance and physicians' age
      (r2=0.002, not significant [NS]) CONCLUSION: Physicians demonstrated only
      moderate knowledge and usage of clinical epidemiology terms used in major medical
      journals. Their capacity to interpret quantitative data from medical scientific
      literature may be limited.

PMID- 16895827
TI  - Do notions of risk inform patient choice? Lessons from a study of prenatal
      genetic counseling.
AB  - Risk modeling is an increasingly important part of clinical medicine; however,
      "risk status" is a complex notion, understood differently by patients and
      clinicians. Patients' ability to make informed choices about clinical procedures
      often requires that they interpret risk statistics, which may be difficult to
      understand and apply. In this article, which is based on a study of prenatal care
      in South Texas, we consider how notions of risk affect patient decisions about
      prenatal genetic testing. The term "risk" carries multiple meanings for
      clinicians and patients. These meanings may conflate concepts of danger and
      probability as well as muddle population risk and individual risk. We propose
      that failure to articulate the varied and contrasting meanings of risk held by
      clinicians and patients can undermine clinical communication and, thereby, hamper
      patients' ability to make autonomous, informed choices. Attending to these
      differences may prove useful in empowering patients to make truly informed
      decisions.

PMID- 16895828
TI  - Medicalization, reproductive agency, and the desire for surgical sterilization
      among low-income women in urban Brazil.
AB  - This article draws on data from ethnographic fieldwork in an urban housing
      project to examine the social context and meanings of surgical sterilization for
      low-income women in Brazil. Low-income women resort to sterilization because they
      distrust or are unsatisfied with alternative methods and because it helps them to
      fulfill the requirements of modern, responsible motherhood. Although
      sterilization is an option among few alternatives, and one that has subjected
      women to greater medical management and intervention, I argue that sterilization
      also represents poor women's active struggle to improve their lives and to resist
      the burdens placed on them by unequal gender relations. This article contributes
      to a growing anthropological literature that demonstrates how reproduction has
      become a central site where social values are constituted and contested, and it
      details women's diverse responses to the process of medicalization.

PMID- 16895829
TI  - "Stress knocks hard on your immune system": asthma and the discourse on stress.
AB  - Stress has been described by anthropologists and other scholars as a problematic
      concept, a discourse, a modern metaphor, a collective representation, and a
      cultural resource. The vast array of academic work in the arena of stress
      research belies the historical reality of stress as an object of inquiry; rather,
      stress is presented as new, the story of its emergence intermingled with
      processes of industrialization, individualism, and perceptions of modern life.
      This article traces the uses to which the concept of stress is put in the illness
      narratives of persons with asthma. It argues that multiple invocations of stress
      not only make visible the workings of personal responsibility and individualism
      regarding chronic illness management in the contemporary United States but also
      gesture toward the social relations of sickness that lie beyond individual
      control.

PMID- 16895830
TI  - Understanding stress through the genome.
AB  - Stress-induced glucocorticoid hormones support coping with and adaptation to
      different stressors. They act to modulate gene expression in a tissue and
      stressor-specific manner through activation of corticosteroid receptors, which
      act as transcription factors. Here, a number of recent insights in gene
      regulation under the influence of glucocorticoids are discussed. Emphasis is put
      on distinct classes of target genes that may be defined, based on categorization
      of (combinations of) transcription factor binding sites in responsive genes.
      These categories depend on insights into different mechanisms of transcriptional
      regulation, such as transactivation vs transrepression, and high affinity vs low
      affinity hormone receptor response elements. It is argued that such classes,
      based on mechanistic understanding of transcription regulation, in combination
      with the availability of complete genomic sequences and expression data from
      different organs, may enhance our understanding of the way in which organisms
      deal with different forms of stress.

PMID- 16895831
TI  - Stress and cardiac beta adrenoceptors.
AB  - Most modern theories about stress recognize that although stress is not a
      disease, it may be the trigger for the majority of diseases when allostatic
      overload has been generated. During stress, the glucocorticoids and
      catecholamines play a key role in the regulation of physiological parameters and
      homeostasis during stress. In the heart, positive chronotropic, inotropic, and
      lusitropic responses to catecholamines are mediated by various subtypes of
      adrenergic receptors (beta-ARs), mainly beta1- and beta2-adrenergic receptors.
      beta-ARs also control cardiomyocyte growth and death, thus contributing to
      cardiac remodelling. The structural basis of each beta-AR subtype, as well as
      their signalling pathways, and adaptive responses to stress are discussed. The
      participation of beta3- and putative beta4-ARs in the control of cardiac function
      is also discussed, with emphasis on low affinity beta-AR isoforms and the role
      they play in the response to the catecholamines under stress. The changes in beta
      AR signalling under pathogenic conditions as well as under stress are reviewed.

PMID- 16895832
TI  - Prenatal stress affects the developmental trajectory of the rat amygdala.
AB  - The amygdala plays a critical role in generating the emotion of fear, and
      alterations in amygdala fear processing are thought to underlie the acquisition
      and maintenance of anxiety disorders. The prenatally stressed (PS) rat displays
      hormonal, behavioral and brain anatomical similarities to anxious humans and is
      useful to study the neurobiological underpinnings of pathological anxiety. We
      studied PS and control male rats at postnatal days 7 (P7), P25, P45 and P60.
      Using unbiased stereological analyses we examined the volumes, anterior-posterior
      lengths and total numbers of neurons and glia of the basolateral (BL), central
      (Ce) and lateral (La) amygdalar nuclei. We found prenatal stress-associated
      differences in the developmental trajectories of each nucleus. These were
      apparent in some measures as early as P7, most extensive at P25 and resolved by
      P45, at least as seen by Nissl staining. These changes were not a result of
      differential brain growth. This early divergence in developmental trajectories
      seen here may be the harbinger of PS rat amygdalas that ultimately function very
      differently in adulthood.

PMID- 16895834
TI  - Circulating leukocyte heat shock protein 70 (HSP70) and oxidative stress markers
      in rats after a bout of exhaustive exercise.
AB  - A novel method to measure oxidative stress resulting from exhaustive exercise in
      rats is presented. In this new procedure we evaluated the erythrocyte antioxidant
      enzymes, catalase (CAT) and glutathione reductase (GR), the plasma oxidative
      attack markers, reactive carbonyl derivatives (RCD) and thiobarbituric reactive
      substances (TBARS). Muscular tissue damage was evaluated by monitoring plasma
      creatine kinase (CK) and plasma taurine (Tau) concentrations. Also, we monitored
      total sulphydryl groups (TSG) and uric acid (UA), and the level of the 70 kDa
      heat shock protein (HSP70) in leukocytes as a marker of oxidative stress. In the
      study we found a correspondence between erythrocyte CAT and GR activities and
      leukocyte HSP70 levels, principally 3 h after the acute exercise, and this
      suggested an integrated mechanism of antioxidant defense. The increase in levels
      of plasma Tau was coincident with the increasing plasma levels of CK and TBARS,
      principally after two hours of exercise. Thus tissue damage occurred before the
      expression of any anti-oxidant system markers and the monitoring of Tau, CK or
      TBARS may be important for the estimation of oxidative stress during exhaustive
      exercise. Furthermore, the integrated analyses could be of value in a clinical
      setting to quantify the extent of oxidative stress risk and reduce the need to
      perform muscle biopsies as a tool of clinical evaluation.

PMID- 16895833
TI  - Chronic corticosterone-induced deterioration in rat behaviour is not paralleled
      by changes in hippocampal NF-kappaB-activation.
AB  - We investigated whether long-lasting stress induced by chronic glucocorticoid
      (GC) exposure affects activation of brain NF-kappaB and whether these changes are
      related to functional deterioration and structural changes in the rat
      hippocampus. Psychometric investigations were conducted using a holeboard test
      system in 28 one-year-old male Wistar rats. Thereafter, rats were divided into
      three groups for daily administration of 10 mg corticosterone (treatment) or
      sesame oil (placebo = sham control for effects of the vehicle) for 60 days.
      Additional control rats did not receive any treatment or handling until the end
      of the experiment. Behavioural and cognitive changes were tested again in the
      holeboard system. Rat body weights and corticosterone concentrations in plasma,
      hippocampus and urine were determined and adrenal glands were investigated
      histopathologically. Hippocampal concentrations of corticosterone, NF-kappaB and
      I-kappaBalpha were determined using RIA, EMSA and Western blotting techniques,
      respectively. Structural changes in rat hippocampus were measured using magnetic
      resonance imaging techniques. High peripheral corticosterone concentrations after
      chronic treatment led to significant reductions in rat body weight. Significant
      atrophy of both adrenal glands with marked histological deterioration was
      detected. Furthermore, an increase in hippocampal corticosterone concentrations
      was observed after chronic administration. Chronic corticosterone treatment also
      significantly altered behaviour and working and reference memory capacity without
      changing hippocampal structure. Daily injections of sesame oil in the placebo
      group, however, were also sufficient to reduce the pellet-finding time. However,
      neither in the corticosterone group nor in the placebo group were behavioural
      changes paralleled by significant changes in brain NF-kappaB activation and I
      kappaBalpha expression. Thus, cognitive alterations in rats seen after chronic
      corticosterone exposure are not paralleled by hippocampal NF-kappaB modulation.

PMID- 16895835
TI  - Exhaustion is differentiable from depression and anxiety: evidence provided by
      the SF-36 vitality scale.
AB  - Stress-related exhaustion is an increasingly focused phenomenon, although
      scientifically not yet fully conceptualised. This is perhaps partly due to the
      fact that the distinction between exhaustion and other already established
      concepts, such as depression, is not clear. This study explores whether
      exhaustion can be differentiated from depression and anxiety, by means of
      introducing the SF-36 vitality scale as a strategy for the measurement of
      exhaustion. The Malmo Shoulder and Neck Study cohort, in this study including
      12,607 middle-aged men and women, was utilized. Depression and anxiety were
      assessed by the general health questionnaire (GHQ). Factor analysis was performed
      in order to potentially discriminate between the included measures. Factor
      analysis showed that all four exhaustion items of the (inverted) SF-36 vitality
      scale loaded on a single factor, separate from the GHQ depression and anxiety
      factors. These results support the notion that exhaustion can be distinguished
      from depression and anxiety, providing an empirical foundation for defining
      exhaustion as a unique concept. Furthermore, since SF-36 has been widely used in
      clinical and epidemiological studies, the benefits of using the SF-36 vitality
      scale in the assessment of exhaustion could be substantial.

PMID- 16895837
TI  - The evaluation of formulations for the preparation of pellets with high drug
      loading by extrusion/spheronization.
AB  - A capillary rheometer was used to evaluate rheological properties and the fluid
      mobility of mixtures with a high drug loading (80%) of three model drugs
      (ibuprofen, lactose, and ascorbic acid) when extruded. These drugs have a range
      of solubility in water, with 20% microcrystalline cellulose (MCC) as the
      spheronization aid, and water, pH 2.0, and pH 10.0 buffer as the binder liquid.
      The results were compared with the ability of the systems to form spherical
      pellets by the process of extrusion/spheronization. It was found possible to
      produce round pellets with a narrow size distribution by the process of
      extrusion/spheronization for formulations containing 80% of either lactose or
      ascorbic acid with MCC as the spheronization aid. It was not, however, possible
      to form pellets containing the same level of ibuprofen. This appears to be
      associated with the high level of fluid mobility observed when the wet masses
      were extruded in a ram extruder. A range of rheological characteristics in terms
      of shear stress, die entry pressure, angles of convergence, extensional flow, and
      elasticity were determined, but the variations in the values of these, which were
      observed, did not give an indication of the ability of the wet mass to form
      spherical pellets when subjected to the spheronization process. This could be
      associated with the fact that the selection of the conditions necessary to
      provide a valid quantification of the extrusion process did not truly represent
      the stability of the systems in terms of the mobility of the fluid when the wet
      mass was processed. The formulation of a wet mass with limited fluid mobility
      appears to be the first priority of formulations used in
      extrusion/spheronization.

PMID- 16895838
TI  - The importance of the cosolvent propylene glycol on the antimicrobial
      preservative efficacy of a pharmaceutical formulation by DOE-ruggedness testing.
AB  - The aim of this study was to statistically evaluate the influence of the
      concentration of the co-solvent propylene glycol on the preservative efficacy of
      a complex pharmaceutical suspension-emulsion formulation containing methyl- and
      propylparaben. Preservative Efficacy Tests (PETs) were performed using the
      validated pharmacopoeial methodology with five test organisms over 1 month on lab
      scale test formulations. These were independently prepared according to a Box
      Behnken experimental design with a triplicate central point at 0.22% m/m
      methylparaben, 0.22% m/m propylparaben, and 2.75% m/m propylene glycol, and with
      an additional corner point of the Box-Behnken cube. We evaluated the preservative
      efficacies against the criteria of the United States Pharmacopeia (USP) and
      European Pharmacopoeias (PhEur) for formulations for oral use, as well as by the
      statistical comparison of the slopes obtained by linear regression of log (CFU/g)
      vs. time. With an initial bacterial challenge of 10(6) CFU/g for each of the
      three bacterial strains, no survivals were detected after 7 days. For the two
      fungal strains, box plots and analysis of variance showed significant,
      concentration-dependent, main effects: the three variables significantly
      influenced the kill-rate of C. albicans, while A. niger was predominantly
      influenced by the cosolvent propylene glycol, and only to a minor extent by
      methylparaben and not at all by propylparaben. These findings were confirmed by
      taking the pharmacopoeial criteria as the evaluation basis, where the dominant
      influence of propylene glycol concentration is apparent. It was concluded that
      the cosolvent propylene glycol is at least of equal preservative importance than
      both parabens.

PMID- 16895839
TI  - Influence of plasticizer level on the drug release from sustained release film
      coated and hot-melt extruded dosage forms.
AB  - In the current study, the influence of plasticizer level on drug release was
      investigated for solid dosage forms prepared by hot-melt extrusion and film
      coating. The properties of two highly water-soluble compounds, diltiazem
      hydrochloride (DTZ) and chlorpheniramine maleate (CPM), and a poorly water
      soluble drug, indomethacin (IDM), were investigated in the melt extrudates
      containing either Eudragit RSPO or Eudragit RD 100 and triethyl citrate (TEC) as
      the plasticizer. In addition, pellets containing DTZ were film coated with
      Eudragit RS 30D and varying levels of TEC using a fluidized bed coating unit.
      Differential scanning calorimetry (DSC) demonstrated that both CPM and IDM
      exhibited a plasticization effect on the acrylic polymers, whereas no
      plasticizing effect by DTZ on Eudragit RSPO was observed. Thermogravimetric
      analysis (TGA) was used to investigate the thermal stability of the DTZ, Eudragit
      RSPO and TEC at 140 degrees C, the maximum temperature used in the hot-melt
      extrusion process. The chemical stability of DTZ and IDM in the extrudate
      following hot-melt processing was determined by high pressure liquid
      chromatography (HPLC). Drug release rates of both DTZ and CPM from hot-melt
      extrudates increased with an increase in the TEC level in the formulations, while
      the release rate of DTZ from the Eudragit RS 30D-coated pellets decreased with an
      increase in TEC in the coating dispersion. This phenomenon was due to the
      formation of a reservoir polymeric structure as a result of the thermal stress
      and shear stress involved in the hot-melt extrusion process regardless of the TEC
      level. In contrast, coalescence of the polymer particles in the film coating
      process was enhanced with higher levels of TEC, as demonstrated by scanning
      electron microscopy (SEM). The addition of TEC (0% to 8%) in the IDM hot-melt
      extrudate formulation had no influence on the drug release rate as the drug
      release rate was controlled by drug diffusion through the inside of the polymeric
      materials rather than between the polymer particles.

PMID- 16895840
TI  - Evaluation of disintegrating time of rapidly disintegrating tablets by a paddle
      method.
AB  - A paddle method for measurement of the disintegrating time of orally
      disintegrating tablets with rizatriptan benzoate as a model drug was evaluated.
      The paddle method employed a dissolution test assembly with tablets immersed in
      disintegrating medium through a fastened sinker. Paddle stirring rate, opening of
      the sinker sieve, and tablet crushing strength influenced disintegrating time
      greatly. A logarithmic relationship was observed between disintegrating time and
      paddle revolution speed, while disintegrating time values and tablet crushing
      strength were fitted to a linear equation. The paddle method values with limited
      deviation were in good correlation with in vivo results. The paddle method was
      employed to optimize the disintegrating time of rizatriptan benzoate orally
      disintegrating tablets using a factorial design. The best-fit quadratic equation
      with a regression coefficient of 0.996 was highly predictive, which was
      indicative that the paddle method was precise and applicable in formulation
      optimization.

PMID- 16895841
TI  - Evaluation of risk and benefit in the implementation of near-infrared
      spectroscopy for monitoring of lubricant mixing.
AB  - On-line near-infrared spectroscopy (NIRS) was used to monitor lubricant blending
      to ensure the quality of the final dosage form. A quantitative multivariate NIR
      model was developed using different lubricant concentration levels. Real-time
      model predictions correlated well with the expected lubricant concentration
      during blending, which allowed determination of blend quality. The significance
      of sensor location on the blender at different fill levels was evaluated. The
      capability of this application was further assessed by real-time study of
      blending dynamics under varying process conditions and raw material attributes.
      The response of the developed NIR method to sudden spikes in analyte
      concentration, changes in raw material attributes, and perturbations to standard
      mixing procedures was evaluated. This study allows an understanding of risk
      factors associated with the implemented technology, and its ability to accurately
      monitor the process events. Furthermore, it highlights the importance of proper
      selection of processing conditions and raw material attributes to improve process
      robustness.

PMID- 16895842
TI  - Evaluation of carbopol-methyl cellulose based sustained-release ocular delivery
      system for pefloxacin mesylate using rabbit eye model.
AB  - The major purpose of this study was to develop and characterize a series of
      carbopol- and methyl cellulose-based solutions as the in situ gelling vehicles
      for ophthalmic drug delivery. The rheological properties, in vitro release as
      well as in vivo pharmacological response of a combination of polymer solutions,
      including carbopol and methyl cellulose, were evaluated. It was found that the
      optimum concentration of carbopol solution for the in situ gel-forming delivery
      systems was 0.3% (w/w), and that for methyl cellulose solution was 1.5% (w/w).
      The mixture of 0.3% carbopol and 1.5% methyl cellulose solutions showed a
      significant enhancement in gel strength in the physiological condition; this gel
      mixture was also found to be free flowing at pH 4.0 and 25 degrees C. The
      rheological behaviors of carbopol/methyl cellulose solution were not affected by
      the incorporation of the drug. Drug levels in the aqueous humor of the rabbits
      were well above the MIC-values of relevant bacteria after 12 hours, the results
      of an optimized formulation containing 0.18% of pefloxacin mesylate compared well
      with the 0.3% marketed eye drop formulation, indicating our formulation to be
      significantly better considering that a similar effect was obtained at half the
      concentration. Both the in vitro release and in vivo pharmacological studies
      indicated that the carbopol/methyl cellulose solution had better ability to
      retain drug than did the carbopol or methyl cellulose solutions alone. The
      results demonstrated that the carbopol/methyl cellulose mixture can be used as an
      in situ gelling vehicle to enhance the ocular bioavailability of pefloxacin
      mesylate.

PMID- 16895843
TI  - Manufacture, characterization, and pharmacodynamic evaluation of engineered
      ipratropium bromide particles.
AB  - PURPOSE: The intent of this research was to generate and characterize respirable
      particles of ipratropium bromide (IPB), a short-acting anticholinergic
      bronchodilator, to achieve demonstrable sustained-release properties. The value
      of a long-acting anticholinergic agent is evident in the use of tiotropium for
      the treatment of chronic obstructive pulmonary disease. METHODS: Hollow,
      spherical particles of ipratropium bromide suitable for inhalation were generated
      using a spray-drying process and characterized by laser diffraction particle size
      analysis, scanning electron microscopy, dynamic vapor sorption, X-ray
      diffraction, differential scanning calorimetry, thermogravimetric analysis, and
      dissolution testing. Experimental design techniques were used to identify
      critical process parameters and optimize the spray drying process.
      Pharmacodynamic studies were conducted to determine duration of effect. RESULTS:
      Crystalline, stable, respirable particles with a range of dissolution profiles
      were manufactured by application of polylactic acid (PLA) coatings of 1, 5, 10,
      15, 30, and 50% w/w. A novel, robust, modified Type IV dissolution method
      discriminated between formulations and guided their development. Preliminary
      studies in guinea pigs indicated an increased duration of bronchodilatory effect
      for 30% PLA-coated particles (56.3 min) particles compared with IPB powders alone
      (11.0 min). CONCLUSIONS: Sustained-release respirable particles of ipratropium
      bromide were developed using a PLA spray coating approach and a trend for
      increased duration of effect was demonstrated in guinea pigs.

PMID- 16895844
TI  - Prediction of dissolution profiles of acetaminophen beads using artificial neural
      networks.
AB  - Immediate release acetaminophen (APAP) beads with 40% drug loading were prepared
      using the extrusion-spheronization process. Eighteen batches of beads were
      prepared based on a full factorial design by varying process variables such as
      extruder type, extruder screw speed, spheronization speed, and spheronization
      time. An in vitro dissolution test was carried out using the USP 27 Apparatus II
      (paddle) method. Artificial Neural Network (ANN) models were developed based on
      the aforementioned process variables and dissolution data. The trained ANN models
      were used to predict the dissolution profiles of APAP from the beads, which were
      prepared with various processing conditions. For training the ANN models, process
      variables were used as inputs, and percent drug released from APAP beads was used
      as the output. The dissolution data from one out of 18 batches of APAP beads was
      selected as the validation data set. The dissolution data of other 17 batches
      were used to train the ANN models using the ANN software (AI Trilogy) with two
      different training strategies, namely, neural and genetic. The validation results
      showed that the ANN model trained with the genetic strategy had better
      predictability than the one trained with the neural strategy. The ANN model
      trained with the genetic strategy was then used to predict the drug release
      profiles of two new batches of APAP beads, which were prepared with process
      variables that were not used during the ANN model training process. However, the
      process variables used to prepare the two new batches of APAP beads were within
      the confines of the process variables used to prepare the 18 batches. The actual
      drug release profile of these two batches of APAP beads was similar to the ones
      predicted by the trained and validated ANN model, as indicated by the high f2
      values. Furthermore, the ANN model trained with genetic strategy was also used to
      optimize process variables to achieve the desired dissolution profiles. These
      batches of APAP beads were then actually prepared using the process variables
      predicted by the trained and validated ANN model. The dissolution results showed
      that the actual dissolution profiles of the APAP beads prepared from the
      predicted process variables were similar to the desired dissolution profiles.

PMID- 16895845
TI  - The nitrogen adsorption isotherm of alpha-lactose monohydrate.
AB  - A complete nitrogen adsorption isotherm was measured for alpha-lactose
      monohydrate, from 0.001 to 0.995 relative pressure at 77 K. The isotherm was
      qualitatively classified as Type II, and was quantitatively analyzed for surface
      area, porosity, and surface heterogeneity. Surface area results revealed that the
      normal Brunauer Emmett Teller (BET) range of 0.05-0.35 relative pressure was not
      suitable for this grade of lactose, but having full isotherm data enabled a more
      appropriate analytical range to be found, illustrating the importance of
      measuring the entire isotherm as an essential step in method development. The
      isotherm was analyzed for micro and mesoporosity, both of which were found to be
      insignificant for lactose. The low relative pressure range 0.001-0.005 did not
      obey Henry's law, indicating the presence of surface heterogeneity. Density
      functional theory was exploited to quantitatively measure heterogeneity in the
      surface energy of lactose, using the full nitrogen adsorption profile. As
      expected for a crystalline material with multiple faces and likely presence of
      imperfections on the surface, the surface energy distribution function was broad
      with more than one mode.

PMID- 16895846
TI  - Thermogravimetric analysis for the determination of water release rate from
      microcrystalline cellulose dry powder and wet bead systems.
AB  - The purpose of this work was to determine the total amount of water contained in
      dry powder and wet bead samples of microcrystalline cellulose, MCC, (Avicel PH
      101), taken from various stages of the extrusion/marumerization process used to
      make beads and to determine the kinetic rates of water release from each sample.
      These samples were allowed to equilibrate in controlled humidity chambers at 25
      degrees C. The total amount of water in each sample, after equilibration, was
      determined by thermogravimetric analysis (TGA) as a function of temperature. The
      rates of water release from these samples were determined by using isothermal
      gravimetric analysis (ITGA) as a function of time. Analysis of the results for
      these studies suggest that water was released from these systems by several
      different kinetic mechanisms. The water release mechanisms for these systems
      include: zero order, second order, and diffusion controlled kinetics. It is
      believed that all three kinetic mechanisms will occur at the same time, however;
      only one mechanism will be prominent. The prominent mechanism was based on the
      amount of water present in the sample.

PMID- 16895847
TI  - Iontophoretic transdermal delivery of haloperidol.
AB  - The in vitro iontophoretic transdermal delivery of haloperidol (HP) across pig
      skin was investigated. Anodal iontophoresis considerably increased HP skin
      penetration and accumulation as compared to the passive controls.The effect of
      NaCl and HP concentrations on the vehicle were also studied. As expected, HP
      iontophoretic transport decreased with NaCl content. On the other hand, HP
      concentration did not modify its electrotransport in the range of concentrations
      between 0.4 and 0.9 mg/mL, except at 24 hours. The influence of the current
      density (0.20-0.50 mA/cm2) was also investigated. The iontophoretic transport of
      HP tends to increase with current density. On the whole, this work shows that
      iontophoresis may be used to improve the topical application of HP for the
      treatment of chronic psychosis.

PMID- 16895848
TI  - Response surface methodology to obtain beta-estradiol biodegradable microspheres
      for long-term therapy of osteoporosis.
AB  - The purpose of this work was to evaluate the main and interaction effects of
      formulation factors on the drug encapsulation efficiency of beta-estradiol
      biodegradable microspheres by applying response surface methodology. A secondary
      purpose was to obtain an optimized formula for long-term therapy of osteoporosis.
      A three factor, three level Box-Behnken experimental design was used to get 15
      experimental runs. The independent variables were drug/polymer ratio (X1),
      dispersing agent concentration (X2), and deaggregating agent concentration (X3).
      The dependent variables were percentage encapsulation efficiency (Y1), cumulative
      percent drug released (Y2), and percentage yield of the microspheres (Y3). The
      formulations were prepared by emulsion solvent evaporation technique using ethyl
      acetate as organic solvent. The optimized formulation was maximized for
      encapsulation efficiency and further characterized for the particle size
      distribution, scanning electron microscopy (SEM), X-ray diffraction (XRD), and
      Fourier transform infrared (FT-IR). The mathematical relationship obtained
      between X1, X2, X3, and Y1 was: Y1 = -129.85 + 29.35X1 + 129.99X2 + 64.82X3 -
      3.2X1X2 - 0.29X1X3 - 35.83X2X3 - 2.05X(2)(1) - 13.23X(2)(2) - 5.92X(2)(3) (R2 =
      0.99) The equation showed that X1, X2, and X3 affect Y1 positively but
      interaction between any two of these factors affects Y1 negatively. The most
      significant interaction was between X2 and X3. The finding indicated that
      controlled releases beta-estradiol biodegradable microspheres with high
      encapsulation efficiency and low pulsatile release can be prepared and the
      quantitative response surface methodology applied helped in understanding the
      effects and the interaction effects between the three factors applied.

PMID- 16895849
TI  - Use of near-infrared for quantitative measurement of viscosity and concentration
      of active ingredient in pharmaceutical gel.
AB  - Near infrared (NIR) spectroscopy is gaining worldwide interest as an analytical
      tool for quality control of raw materials, intermediate products, and final
      dosage forms. This technique can be used without sample preparation, therefore,
      avoiding the need for reagents and solvents. Quantitative NIR analyses involve
      calibration by sophisticated mathematical techniques that have been used
      extensively since the advent of microcomputing and chemometrics. The main
      objective of this investigation was to use transmission near-Infrared
      spectroscopy to measure the potency of an active ingredient in a topical gel
      preparation. A second objective was to evaluate the effect of gel viscosity on
      the NIR reflectance spectra. Four gel formulations with different ibuprofen
      concentrations were used for quantitative determination of the active ingredient,
      and five gel formulations with different viscosity values were used for the
      evaluation of the effect of viscosity change on the near-infrared reflectance
      spectra. The laboratory ibuprofen quantitative determination was compared to near
      infrared transmission data using linear, quadratic, cubic and partial least
      square techniques to determine the relationship between ultraviolet (UV)
      determination and near-infrared spectra. For viscosity, the laboratory data were
      compared to near-infrared diffuse reflectance data using the same techniques used
      to determine the relationship between Brookfield viscometer determination and
      near-infrared spectra. The results demonstrated that an increase in ibuprofen
      concentration and viscosity produced an increase in near-infrared absorbance.
      Series of model equations were developed from the calibration of laboratory vs.
      the near-infrared data for each formulation. The near-infrared spectroscopy
      method is an alternative method that does not require sample pretreatment for
      quantitative measurement of active ingredient and viscosity of pharmaceutical
      gel.

PMID- 16895853
TI  - Clinical validation of the General Ability Index--Estimate (GAI-E): estimating
      premorbid GAI.
AB  - The clinical utility of the General Ability Index--Estimate (GAI-E; Lange,
      Schoenberg, Chelune, Scott, & Adams, 2005) for estimating premorbid GAI scores
      was investigated using the WAIS-III standardization clinical trials sample (The
      Psychological Corporation, 1997). The GAI-E algorithms combine Vocabulary,
      Information, Matrix Reasoning, and Picture Completion subtest raw scores with
      demographic variables to predict GAI. Ten GAI-E algorithms were developed
      combining demographic variables with single subtest scaled scores and with two
      subtests. Estimated GAI are presented for participants diagnosed with dementia (n
      = 50), traumatic brain injury (n = 20), Huntington's disease (n = 15),
      Korsakoff's disease (n = 12), chronic alcohol abuse (n = 32), temporal lobectomy
      (n = 17), and schizophrenia (n = 44). In addition, a small sample of participants
      without dementia and diagnosed with depression (n = 32) was used as a clinical
      comparison group. The GAI-E algorithms provided estimates of GAI that closely
      approximated scores expected for a healthy adult population. The greatest
      differences between estimated GAI and obtained GAI were observed for the single
      subtest GAI-E algorithms using the Vocabulary, Information, and Matrix Reasoning
      subtests. Based on these data, recommendations for the use of the GAI-E
      algorithms are presented.

PMID- 16895854
TI  - Development of WAIS-III General Ability Index Minus WMS-III memory discrepancy
      scores.
AB  - Analysis of the discrepancy between intellectual functioning and memory ability
      has received some support as a useful means for evaluating memory impairment. In
      recent additions to Wechlser scale interpretation, the WAIS-III General Ability
      Index (GAI) and the WMS-III Delayed Memory Index (DMI) were developed. The
      purpose of this investigation is to develop base rate data for GAI-IMI, GAI-GMI,
      and GAI-DMI discrepancy scores using data from the WAIS-III/WMS-III
      standardization sample (weighted N = 1250). Base rate tables were developed using
      the predicted-difference method and two simple-difference methods (i.e.,
      stratified and non-stratified). These tables provide valuable data for clinical
      reference purposes to determine the frequency of GAI-IMI, GAI-GMI, and GAI-DMI
      discrepancy scores in the WAIS-III/WMS-III standardization sample.

PMID- 16895852
TI  - The TCN/AACN 2005 "salary survey": professional practices, beliefs, and incomes
      of U.S. neuropsychologists.
AB  - Doctoral-level members of Division 40 (Clinical Neuropsychology) of the American
      Psychological Association and other neuropsychologists were invited to
      participate in a web-based survey in early 2005. Response rate was estimated to
      be between 28.5 and 31.3%. The range of years postdoctorate was 1-51.
      Demonstrating the substantial proportional change in gender taking place in the
      field, 7 of 10 postdoctoral residents were women. Whereas the median age of APA
      members has been over 50 since the early 1990s, the current median age of
      clinical neuropsychologists is 47 and has essentially remained unchanged since
      1994, indicating substantial entrance of young psychologists into the field. Use
      of testing assistants remains commonplace. The "flexible battery" approach has
      increased in popularity and predominates, whereas endorsement of the
      "standardized battery" approach continues to decline. More than 90% of
      respondents are engaged in full-time or full-time plus part-time employment.
      Incomes from 2004 vary considerably by years of clinical practice, work setting,
      amount of forensic practice, and region of country. Job satisfaction has little
      relationship to income and is comparable across most variables (e.g., work
      setting, professional identity, amount of forensic activity), whereas income
      satisfaction has a stronger relationship to actual income, at least at the higher
      income levels. Job satisfaction of neuropsychologists in general is higher than
      reported for other U.S. jobs. Fewer than one in five respondents is considering
      changing job position and very few individuals are considering leaving
      neuropsychology or psychology for a different field. More than 8 of 10
      respondents experienced an income increase in the last five years, whereas fewer
      than 1 in 10 experienced a decrease. While higher than reported by other types of
      psychologists, neuropsychology incomes have lagged behind inflation when compared
      to 1992 data. Numerous breakdowns related to income and professional activities
      are provided.

PMID- 16895855
TI  - Demographically adjusted normative standards for new indices of performance on
      the Paced Auditory Serial Addition Task (PASAT).
AB  - The Paced Auditory Serial Addition Task (PASAT) is a complex cognitive test
      sensitive to neuropsychological disorders. Its traditional Total Correct score
      seemingly reflects multiple cognitive abilities, including attention, working
      memory, and processing speed. Snyder, Aniskiewicz, and Snyder (1993) modified
      scoring guidelines for the PASAT to give credit only for "dyads." This method
      emphasizes working memory operations and has been found superior to Total Correct
      scores at detecting cognitive impairments in several investigations. To date,
      normative standards are not available for the "dyad" scoring method, thus
      limiting its utility in clinical and research settings. The current investigation
      provides demographically adjusted normative data based on a sample of 500 healthy
      adults of varied age, education, sex, and race (African American and Caucasian)
      for various indices of performance on the PASAT, including "Total Dyads" obtained
      across the four PASAT trials. In addition, we describe and present normative data
      on four other indices designed to quantify various aspects of performance on the
      PASAT: invalid responding, effects of varied information processing speed
      demands, and tendency to omit responses and to make arithmetic errors.

PMID- 16895856
TI  - The psychometric equivalence of two alternate forms of the Controlled Oral Word
      Association Test.
AB  - The equivalence of forms CFL and PRW of the Controlled Oral Word Association Test
      (COWAT; Benton, de Hamsher, & Sivan; 1994) was examined in samples of healthy
      college students. Both novel words and qualitative scores (e.g., clusters,
      switches) were examined using null hypothesis statistical testing (NHST) and
      inferential confidence intervals (Tryon, 2001). Study 1 used a within-subjects
      design (n = 66) to examine form equivalence in persons who completed versions CFL
      and PRW. No mean differences were found for any index, and only one (mean cluster
      size) differed when examining the standard deviations across forms. Inferential
      confidence intervals were constructed and Rg (maximum probable difference) values
      were small and, when compared to prior research, less than the standard error of
      measure associated with using a single form. In Study 2, we employed a between
      subjects design (n = 208) and found that the use of each version generated
      comparable normative data and correlations among scores. These studies suggest
      that versions CFL and PRW are best viewed as alternate (rather than parallel)
      forms at this time; however, they are likely to produce comparable results for
      most purposes. We discuss the use of inferential confidence intervals to examine
      form equivalence and directions for future work.

PMID- 16895857
TI  - Cognitive functioning and everyday problem solving in older adults.
AB  - The relationship between cognitive functioning and a performance-based measure of
      everyday problem-solving, the Everyday Problems Test (EPT), thought to index
      instrumental activities of daily living (IADL), was examined in 291 community
      dwelling non-demented older adults. Performance on the EPT was found to vary
      according to age, cognitive status, and education. Hierarchical regression
      analyses revealed that, after adjusting for demographic and health variables,
      measures of cognitive functioning accounted for 23.6% of the variance in EPT
      performance. In particular, measures of global cognitive status, cognitive
      decline, speed of processing, executive functioning, episodic memory, and verbal
      ability were significant predictors of EPT performance. These findings suggest
      that cognitive functioning along with demographic variables are important
      determinants of everyday problem-solving.

PMID- 16895858
TI  - Patient-informant agreement on personality ratings and self-awareness after head
      injury.
AB  - To address concerns about self-awareness deficits and the validity of self
      ratings by patients with head injury (HI), the current study examines mean
      differences and correlations between self-ratings from 52 patients with HI and
      ratings of the patient by informants using the revised NEO Personality Inventory
      (NEO-PI-R). Patient self-ratings were significantly lower than informant ratings
      on neuroticism and extraversion and significantly higher on conscientiousness.
      Patient-informant correlations ranged from .42 for conscientiousness to .67 for
      agreeableness, and these agreement correlations compare favorably with those
      obtained from normal adult samples. Hierarchical multiple regression equations
      for each of the five NEO-PI-R trait domains showed that more severe injuries were
      associated with higher agreement for extraversion. For all five traits, the
      strongest predictors of informant personality ratings were the patients' self
      ratings. The implications of these findings for clinical assessment and improved
      research on self-awareness deficits after HI are discussed.

PMID- 16895859
TI  - Deviant strategy on The Modified Six Elements Test in patients with
      schizophrenia.
AB  - Impaired executive functioning is found in a considerable proportion of
      schizophrenia patients. Neuropsychological tests are originally designed to
      measure the behavior of neurological patients and may therefore miss psychiatry
      related cognitive deficits. Qualitative information on tests for executive
      functioning is important in psychiatric populations. The Modified Six Elements
      Test (MSET) is a planning test that consists of 6 tasks, for which subjects have
      limited time and have to obey to switching rules. This study concerns a
      qualitatively different approach schizophrenia patients use on the MSET, and its
      relationship with cognitive measures. MSET scores and strategies of schizophrenia
      patients were compared to those of healthy controls, closed-head-injury patients,
      and peripheral injury patients. Also, schizophrenia patients and healthy controls
      were compared on verbal memory and vigilance. Schizophrenia patients finish fewer
      assignments on the MSET, receive a lower profile score compared to healthy
      controls, and use a different strategy on the test compared to the other groups.
      They also perform below healthy controls on the tests for verbal memory and
      vigilance. Use of the different strategy in schizophrenia patients was related to
      impaired cognitive functioning. An interesting strategy used by schizophrenia
      patients on the MSET appears to be indicative of impaired cognitive functioning.
      This strategy may be a compensatory strategy to spare cognitive resources. It
      could also be the result of a concrete interpretation of the test instructions.

PMID- 16895860
TI  - Differential impact of executive function on visual memory tasks.
AB  - Despite their common use in neuropsychological evaluation, little is known about
      the differential contribution of executive functioning to visual memory tests. In
      this study, hierarchical regression was used to determine the role of executive
      functioning on the Visual Reproduction subtest of the Wechsler Memory Scale-
      Third Edition, and the Rey-Osterrieth Complex Figure (ROCF) in a mixed
      neurological sample of 193 patients. Executive functioning was predictive of
      Visual Reproduction but not ROCF recall variables after accounting for
      demographic variables and global cognitive functioning. Only executive tests with
      a visuospatial component, the Trail-Making Test Part B and Wisconsin Card Sorting
      Test perseverative responses, were predictive of recall of Visual Reproduction
      stimuli. Organization of the ROCF was predictive of both Visual Reproduction and
      ROCF recall. These findings increase our understanding of the executive
      contribution to two common visual memory tests and may aid in the clinical
      interpretation of seemingly discrepant visual memory performance.

PMID- 16895861
TI  - Sensitivity and specificity of MMPI-2 validity scales and indicators to
      malingered neurocognitive dysfunction in traumatic brain injury.
AB  - The present study used a known-groups design to determine the classification
      accuracy of 10 MMPI-2 validity scales and indicators in the detection of
      cognitive malingering in traumatic brain injury. Participants were 259 traumatic
      brain injury and 133 general clinical patients seen for neuropsychological
      evaluation. The TBI patients were subdivided into groups based on a comprehensive
      examination of effort following Slick, Sherman, and Iverson's (1999) criteria.
      More extreme scores demonstrated excellent specificity; often impressive
      sensitivity was seen even while maintaining a low false positive error rate.
      Specificity was good even in stroke, memory disorder, and psychiatric patients
      without incentive. The results of this study are presented in frequency tables
      that can be easily referenced in clinical practice.

PMID- 16895863
TI  - Replication of the Test of Memory Malingering (TOMM) in a traumatic brain injury
      and head trauma sample.
AB  - The purpose of the current study was to replicate the clinical validation study
      of the Test of Memory Malingering (Tombaugh, 19961997). Fifty cases were selected
      from two different participant pools: medically documented traumatic brain-injury
      patients and compensation-seeking, mild head trauma cases. Results replicated and
      expanded those found by Tombaugh and indicated that employing a Trial 2 cutting
      score of greater than 5 errors provided adequate sensitivity to suboptimal effort
      while demonstrating remarkable insensitivity to cognitively impaired traumatic
      brain-injury cases. Use of a lower cutting score (e.g., 2 to 5 errors) is also
      discussed.

PMID- 16895862
TI  - Detecting incomplete effort with Digit Span from the Wechsler Adult Intelligence
      Scale-Third Edition.
AB  - The current study evaluated the utility of the Digit Span subtest in
      discriminating patients with mild head trauma from individuals referred for
      independent neuropsychological evaluation with objective evidence of poor effort.
      Various indices from the Digit Span subtest were evaluated to determine the best
      discriminator of brain injury from poor motivation patient groups: Digit Span
      Forward, Digit Span Backwards, Reliable Digit Span, Digit Span Age-Corrected
      Scaled Score, and the difference score between the Vocabulary and Digit Span
      scaled scores. The Digit Span scaled score was found to be the best
      discriminating index. A cutoff score of less than or equal to 7 accurately
      classified 75% of persons in the incomplete effort group and 69% of persons in
      the TBI group. Application of this cutoff score to a non-litigating mild brain
      injury group yielded a 77% correct classification rate. However, Digit Span
      scaled score accounted for a modest amount of variation and it is not recommended
      as a stand-alone validity measure.

PMID- 16895864
TI  - Estimating the predictive value of the Test of Memory Malingering: an
      illustrative example for clinicians.
AB  - Recent years have witnessed an explosion in the amount of research literature
      dedicated to the identification of symptom exaggeration and/or malingering in
      neuropsychological assessments. Additionally, there is now a growing literature
      devoted to estimating the base rates of symptom exaggeration/malingering in a
      range of populations and settings. However, very little literature has been
      devoted to estimating the positive predictive value (PPV) or negative predictive
      value (NPV) of these assessment devices and/or strategies. The current project
      was conducted to provide an illustrative example of how to use the research
      literature to calculate both PPV and NPV in everyday clinical practice. When the
      Word Memory Test (WMT) was used as the "gold standard" to which the Test of
      Memory Malingering (TOMM) was compared, the TOMM achieved very high PPV (.98) and
      acceptable NPV (.78). How to incorporate the strategy used into clinical practice
      is discussed.

PMID- 16895865
TI  - Application of the new MMPI-2 Malingered Depression scale to individuals
      undergoing neuropsychological evaluation: relative lack of relationship to
      secondary gain and failure on validity indices.
AB  - The Malingered Depression (Md) scale for the MMPI-2 (Steffan, Clopton, & Morgan,
      2003) was recently developed to detect attempts at malingering depressive
      symptomatology. The Steffan et al. cutoffs for the Md scale were derived through
      comparisons of undergraduate malingering simulators with depressed
      undergraduates. In order to explore the potential utility for neuropsychological
      practice, we examined the Md scale among 160 individuals with and without a
      context of secondary gain referred for neuropsychological evaluation. Md results
      were compared to other MMPI-2 validity indices and performance on effort testing.
      While Md was found to correlate highly with other validity indices from the MMPI
      2, it was also correlated significantly with measures of depression, both in
      individuals with and without a secondary gain context. Md scores were not
      significantly different between secondary gain and no secondary gain groups,
      whereas FBS and L were significantly different. The effect of passing or failing
      validity indicators on rates of Md scores exceeding the Steffan et al. cutoffs
      was limited. Only among the few individuals exceeding a high threshold on the F
      scale or combinations of F, FBS, and effort indicators was it common to also
      surpass the Md cutoff. Overall, Md showed relatively little relationship to
      either secondary gain status or cognitive malingering in our sample. Given that
      such factors do not necessarily produce high scores on Md, the utility of the
      scale to clinical neuropsychologists appears low.

PMID- 16895866
TI  - Performance of patients with epilepsy or psychogenic non-epileptic seizures on
      four measures of effort.
AB  - Exaggeration of cognitive symptoms or poor effort on cognitive testing has been
      addressed primarily in the traumatic brain injury literature. The present
      investigation aims to extend the evaluation of effort to the epilepsy monitoring
      setting, where base rates of failure on effort testing remain unknown for
      patients with intractable epilepsy (ES), psychogenic nonepileptic seizures
      (PNES), or both conditions (ES+PNES). In addition, this investigation explores
      how well four measures of effort (DMT, LMT, TOMM, PDRT) distinguish between these
      diagnostic groups. Results show that 20% of the combined sample failed one or
      more effort measure. When examining failure rates for each diagnostic group, 22%
      of epilepsy patients, 24% of PNES patients, and 11% of ES+PNES patients performed
      suboptimally on one or more measure of effort. The utility of these effort
      measures to differentiate between these diagnostic groups appears limited.
      Further research is needed to clarify the base rate of poor effort in the
      epilepsy monitoring unit setting in general and in these three diagnostic groups
      specifically.

PMID- 16895871
TI  - Early nutritional determinants of coronary artery disease: a question of timing?

PMID- 16895872
TI  - Vitamin D deficiency during pregnancy: an ongoing epidemic.

PMID- 16895874
TI  - Global nutrition dynamics: the world is shifting rapidly toward a diet linked
      with noncommunicable diseases.
AB  - Global energy imbalances and related obesity levels are rapidly increasing. The
      world is rapidly shifting from a dietary period in which the higher-income
      countries are dominated by patterns of degenerative diseases (whereas the lower-
      and middle-income countries are dominated by receding famine) to one in which the
      world is increasingly being dominated by degenerative diseases. This article
      documents the high levels of overweight and obesity found across higher- and
      lower-income countries and the global shift of this burden toward the poor and
      toward urban and rural populations. Dietary changes appear to be shifting
      universally toward a diet dominated by higher intakes of animal and partially
      hydrogenated fats and lower intakes of fiber. Activity patterns at work, at
      leisure, during travel, and in the home are equally shifting rapidly toward
      reduced energy expenditure. Large-scale decreases in food prices (eg, beef
      prices) have increased access to supermarkets, and the urbanization of both urban
      and rural areas is a key underlying factor. Limited documentation of the extent
      of the increased effects of the fast food and bottled soft drink industries on
      this nutrition shift is available, but some examples of the heterogeneity of the
      underlying changes are presented. The challenge to global health is clear.

PMID- 16895875
TI  - Relations of total physical activity and intensity to fitness and fatness in
      children: the European Youth Heart Study.
AB  - BACKGROUND: It is unclear how the amount and intensity of physical activity (PA)
      are associated with cardiovascular fitness (CVF) and body fatness in children.
      OBJECTIVE: We aimed to examine the associations of total PA and intensity levels
      to CVF and fatness in children. DESIGN: A cross-sectional study of 780 children
      aged 9-10 y from Sweden and Estonia was conducted. PA was measured by
      accelerometry and was expressed as min/d of total PA, moderate PA, and vigorous
      PA. CVF was measured with a maximal ergometer bike test and was expressed as
      W/kg. Body fat was derived from the sum of 5 skinfold-thickness measurements.
      Multiple regression analysis was used to determine the degree to which variance
      in CVF and body fat was explained by PA, after control for age, sex, and study
      location. RESULTS: Lower body fat was significantly associated with higher levels
      of vigorous PA, but not with moderate or total PA. Those children who engaged in
      >40 min vigorous PA/d had lower body fat than did those who engaged in 10-18 min
      vigorous PA/d. Total PA, moderate PA, and vigorous PA were positively associated
      with CVF. Those children who engaged in >40 min vigorous PA/d had higher CVF than
      did those who accumulated <18 min vigorous PA/d. CONCLUSIONS: The results suggest
      that PA of vigorous intensity may have a greater effect on preventing obesity in
      children than does PA of lower intensity, whereas both total and at least
      moderate to vigorous PA may improve children's CVF.

PMID- 16895873
TI  - Intake of sugar-sweetened beverages and weight gain: a systematic review.
AB  - Consumption of sugar-sweetened beverages (SSBs), particularly carbonated soft
      drinks, may be a key contributor to the epidemic of overweight and obesity, by
      virtue of these beverages' high added sugar content, low satiety, and incomplete
      compensation for total energy. Whether an association exists between SSB intake
      and weight gain is unclear. We searched English-language MEDLINE publications
      from 1966 through May 2005 for cross-sectional, prospective cohort, and
      experimental studies of the relation between SSBs and the risk of weight gain
      (ie, overweight, obesity, or both). Thirty publications (15 cross-sectional, 10
      prospective, and 5 experimental) were selected on the basis of relevance and
      quality of design and methods. Findings from large cross-sectional studies, in
      conjunction with those from well-powered prospective cohort studies with long
      periods of follow-up, show a positive association between greater intakes of SSBs
      and weight gain and obesity in both children and adults. Findings from short-term
      feeding trials in adults also support an induction of positive energy balance and
      weight gain by intake of sugar-sweetened sodas, but these trials are few. A
      school-based intervention found significantly less soft-drink consumption and
      prevalence of obese and overweight children in the intervention group than in
      control subjects after 12 mo, and a recent 25-week randomized controlled trial in
      adolescents found further evidence linking SSB intake to body weight. The weight
      of epidemiologic and experimental evidence indicates that a greater consumption
      of SSBs is associated with weight gain and obesity. Although more research is
      needed, sufficient evidence exists for public health strategies to discourage
      consumption of sugary drinks as part of a healthy lifestyle.

PMID- 16895876
TI  - Preoperative weight loss with a very-low-energy diet: quantitation of changes in
      liver and abdominal fat by serial imaging.
AB  - BACKGROUND: A very-low-energy diet (VLED) can result in substantial, rapid weight
      loss and is increasingly prescribed before obesity surgery to minimize risk and
      difficulty by reducing liver size and abdominal adiposity. Despite its growing
      popularity, a VLED in this setting has received little attention. OBJECTIVE: The
      aim of this study was to investigate the efficacy and acceptability of a
      preoperative VLED. DESIGN: In a prospective observational study, 32 subjects (n =
      19 men and 13 women) with a mean (+/-SD) age of 47.5 +/- 8.3 y and a body mass
      index (in kg/m(2)) of 47.3 +/- 5.3 consumed a VLED for 12 wk. Primary outcomes
      included changes in liver volume (LV) and in visceral and subcutaneous adipose
      tissue (VAT/SAT). Changes in body weight, anthropometric measures, and
      biochemical variables were also recorded, and compliance with, acceptability of,
      and side effects of treatment were assessed. Changes in LV and VAT/SAT area were
      measured by computed tomography and magnetic resonance imaging at baseline and
      weeks 2, 4, 8, and 12. RESULTS: Mean (+/-SD) LV, VAT/SAT, and body weight
      decreased significantly (P < 0.001 for all). The degree of LV reduction was
      directly related to the reduction in relative body weight (r = 0.54, P = 0.001)
      and initial LV (r = 0.43, P = 0.015). Eighty percent of the reduction in LV
      occurred between weeks 0 and 2 (P < 0.001). Reductions in body weight and VAT
      were uniform over the 12-wk period. Attrition was 14%. Acceptability was adequate
      but waned over time, and mild transitory side effects occurred. CONCLUSIONS:
      Given the observed early reduction in LV and the progressive reduction in VAT, we
      suggest that the minimum duration for a preoperative VLED be 2 wk. Ideally, the
      duration should be 6 wk to achieve maximal LV reduction and significant
      reductions in VAT and body weight without compromising compliance and
      acceptability.

PMID- 16895877
TI  - Dietary sphingolipids lower plasma cholesterol and triacylglycerol and prevent
      liver steatosis in APOE*3Leiden mice.
AB  - BACKGROUND: The prevalence of dyslipidemia and obesity resulting from excess
      energy intake and physical inactivity is increasing. The liver plays a pivotal
      role in systemic lipid homeostasis. Effective, natural dietary interventions that
      lower plasma lipids and promote liver health are needed. OBJECTIVE: Our goal was
      to determine the effect of dietary sphingolipids on plasma lipids and liver
      steatosis. DESIGN: APOE*3Leiden mice were fed a Western-type diet supplemented
      with different sphingolipids. Body cholesterol and triacylglycerol metabolism as
      well as hepatic lipid concentrations and lipid-related gene expression were
      determined. RESULTS: Dietary sphingolipids dose-dependently lowered both plasma
      cholesterol and triacylglycerol in APOE*3Leiden mice; 1% phytosphingosine (PS)
      reduced plasma cholesterol and triacylglycerol by 57% and 58%, respectively. PS
      decreased the absorption of dietary cholesterol and free fatty acids by 50% and
      40%, respectively, whereas intestinal triacylglycerol lipolysis was not affected.
      PS increased hepatic VLDL-triacylglycerol production by 20%, whereas plasma
      lipolysis was not affected. PS increased the hepatic uptake of VLDL remnants by
      60%. Hepatic messenger RNA concentrations indicated enhanced hepatic lipid
      synthesis and VLDL and LDL uptake. The net result of these changes was a strong
      decrease in plasma cholesterol and triacylglycerol. The livers of 1% PS-fed mice
      were less pale, 22% lighter, and contained 61% less cholesteryl ester and 56%
      less triacylglycerol than livers of control mice. Furthermore, markers of liver
      inflammation (serum amyloid A) and liver damage (alanine aminotransferase)
      decreased by 74% and 79%, respectively, in PS-fed mice. CONCLUSION: Sphingolipids
      lower plasma cholesterol and triacylglycerol and protect the liver from fat- and
      cholesterol-induced steatosis.

PMID- 16895878
TI  - Early onset of coronary artery disease after prenatal exposure to the Dutch
      famine.
AB  - BACKGROUND: Limited evidence suggests that maternal undernutrition at the time of
      conception is associated with increased cardiovascular disease risk in adult
      offspring. OBJECTIVE: We investigated whether persons conceived during the Dutch
      famine of World War II had an early onset of coronary artery disease (CAD).
      DESIGN: We compared the age at onset and cumulative incidence of CAD between
      persons born as term singletons who were exposed to the 1944-1945 Dutch famine
      during late (n = 160), mid- (n = 138), or early (n = 87) gestation and 590
      unexposed subjects at age 50 or 58 y. Age at CAD onset was defined as the age at
      which angina pectoris was identified (according to the Rose questionnaire), Q
      waves were observed on an electrocardiogram (Minnesota codes 1-1 or 1-2), or
      coronary revascularization was performed (by angioplasty or bypass surgery).
      RESULTS: Of the 83 CAD cases identified, persons conceived during the famine were
      3 y younger than the unexposed persons at the time of CAD diagnosis (47 y
      compared with 50 y) and had a higher cumulative incidence of CAD [13%; hazard
      ratio (HR) adjusted for sex: 1.9; 95% CI: 1.0, 3.8] than did the unexposed
      persons. The HR changed little after adjustment for smoking (HR: 1.8), social
      class (HR: 2.0), or size at birth (HR: 2.0). CONCLUSIONS: We found an earlier
      onset of CAD among persons conceived during the famine, which suggests that
      maternal nutrition in early gestation may play a role in the onset of CAD. This
      finding agrees with evidence from animal experiments that identify
      periconceptional maternal diet as important in the offspring's adult health.

PMID- 16895879
TI  - Adherence to the Mediterranean dietary pattern is positively associated with
      plasma adiponectin concentrations in diabetic women.
AB  - BACKGROUND: Although the typical diet of the Mediterranean region has received
      much recognition over the past several years for its association with substantial
      health benefits, it remains unknown whether its favorable effects are mediated
      through changes in adiponectin concentrations. OBJECTIVE: The objective was to
      determine whether adherence to a Mediterranean-type diet is associated with
      higher plasma adiponectin concentrations. DESIGN: This study was a prospective
      and cross-sectional evaluation of plasma adiponectin concentrations and dietary
      data from 987 diabetic women from the Nurses' Health Study who had no history of
      cardiovascular disease at the time blood was drawn in 1990. RESULTS: Women who
      scored highest on a 9-point scale that measures adherence to a Mediterranean-type
      dietary pattern tended to be older, were less likely to be current smokers, had
      lower body mass indexes and waist circumferences, and had higher total energy
      intakes, physical activities, and plasma adiponectin concentrations than did
      women with the lowest scores. Median plasma adiponectin concentrations were 23%
      higher in women who most closely followed a Mediterranean-type diet than in low
      adherers after adjustment for age and energy intake (P < 0.01). Body composition,
      lifestyle, and medical history explained some, but not all, of the observed
      association between diet and adiponectin concentrations because high adherers
      tended to have greater adiponectin concentrations than did moderate or low
      adherers, even after adjustment for these variables. CONCLUSIONS: Our data
      suggest that, of the several components of the Mediterranean dietary pattern
      score, alcohol, nuts, and whole grains show the strongest association with
      adiponectin concentrations. Close adherence to a Mediterranean-type diet is
      associated with higher adiponectin concentrations.

PMID- 16895880
TI  - Association of plasma free fatty acids and left ventricular diastolic function in
      patients with clinically severe obesity.
AB  - BACKGROUND: Obesity is an important contributor to many cardiovascular risk
      factors and has been associated with abnormalities in cardiac contractile
      function. Causes of impaired contractile function are not fully understood and
      may include an oversupply of substrates. OBJECTIVE: We tested the hypothesis that
      metabolic dysregulation may adversely influence cardiac function. Specifically,
      we examined the effects of plasma free fatty acids and insulin sensitivity on
      left ventricular function in patients with clinically severe obesity. DESIGN: We
      measured metabolic and cardiac variables in 64 obese patients [body mass index
      (BMI; in kg/m(2)) > 35], including 2-D complete echocardiogram with M-mode and
      tissue Doppler imaging, anthropometric measurements, and analysis of blood
      chemistries. RESULTS: The median (25th and 75th percentile) age and BMI were 46 y
      (36, 53 y) and 51.5 (42.5, 56.5), respectively. The prevalence of diabetes,
      hypertension, and insulin resistance were 38%, 53%, and 90%, respectively. Plasma
      free fatty acid (FFA) concentrations were elevated in the cohort. No association
      was observed between insulin sensitivity or anthropometric measurements and left
      ventricular contractile function. However, FFA concentration was independently
      associated with diastolic function (r = -0.33, P = 0.01), and 40% of the cohort
      showed age-adjusted diastolic impairment as measured by tissue Doppler imaging.
      CONCLUSION: The negative association between FFA and diastolic function, in the
      setting of insulin resistance, suggests that excess FFA may exert a lipotoxic
      effect on the heart.

PMID- 16895881
TI  - Ratio of oleic to palmitic acid is a dietary determinant of thrombogenic and
      fibrinolytic factors during the postprandial state in men.
AB  - BACKGROUND: The nature of dietary fats affects the postprandial activation of the
      hemostatic system. OBJECTIVE: We investigated whether the ratio of oleic to
      palmitic acid [and that of monounsaturated to saturated fatty acids (MUFA:SFA)]
      in the diet affects postprandial concentrations of triacylglycerols, tissue
      factor (TF), fibrinogen, tissue-type plasminogen activator (t-PA), and
      plasminogen activator inhibitor 1 (PAI-1). DESIGN: We studied the effects of
      diets enriched in olive oil (ROO), high-palmitic sunflower oil (HPSO), butter, or
      a mixture of vegetable and fish oils (VEFO) on circulating concentrations of the
      aforementioned factors in 14 healthy men. The fats had ratios of oleic to
      palmitic acid (MUFA:SFA) of 6.83 (5.43), 2.36 (2.42), 0.82 (0.48), and 13.81
      (7.08). RESULTS: The largest and longest-lasting postprandial changes in plasma
      triacylglycerol concentrations were found with the butter-based diet (all P <
      0.05). No correlation was observed between the net incremental area under the
      curve (netAUC) for triacylglycerol and the ratio of oleic to palmitic acid (or
      MUFA:SFA) in the dietary fats. The netAUCs for TF and PAI-1, however, were
      inversely related to the ratio of oleic to palmitic acid (and MUFA:SFA) in ROO,
      HPSO, butter, and VEFO. Similar results were found for the fibrinogen netAUC when
      VEFO was omitted from the analysis. The netAUC for t-PA was inversely correlated
      with postprandial concentrations of triacylglycerol. CONCLUSIONS: Postprandial
      concentrations of TF, fibrinogen, and PAI-1 are associated with the ratio of
      oleic to palmitic acid (MUFA:SFA) in dietary fats. The postprandial t-PA response
      is related to postprandial concentrations of triacylglycerol.

PMID- 16895882
TI  - High prevalence of vitamin D deficiency in pregnant non-Western women in The
      Hague, Netherlands.
AB  - BACKGROUND: Vitamin D deficiency is common in dark-skinned persons living in
      northern countries. Vitamin D deficiency during pregnancy may have serious
      consequences for both mother and child. OBJECTIVE: The objective was to ascertain
      the prevalence of vitamin D deficiency in pregnant women of several ethnic
      backgrounds who were living in The Hague, a large city in the Netherlands.
      DESIGN: Midwives whose practice was visited by a large number of non-Western
      immigrants added the assessment of serum 25-hydroxyvitamin D [25(OH)D] to the
      standard blood test given to women who visited the practice during week 12 of
      pregnancy. Subsequently, the Municipal Health Service collected additional data
      from the midwives' files (June 2002 through March 2004): background variables,
      use of tobacco or alcohol or drugs, and infectious diseases. The women were
      grouped ethnically as Western, Turkish, Moroccan, and other non-Western. RESULTS:
      The vitamin D concentrations of 358 women were found in the midwives' files. Of
      these women, 29% were Western, 22% were Turkish, and 19% were Moroccan. Mean
      serum 25(OH)D concentrations in Turkish (15.2 +/- 12.1 nmol/L), Moroccan (20.1 +/
      13.5 nmol/L), and other non-Western women (26.3 +/- 25.9 nmol/L) were
      significantly (P </= 0.001) lower than those in Western women (52.7 +/- 21.6
      nmol/L). Serum 25(OH)D was below the detection limit in 22% of the Turkish women.
      The differences between ethnic groups were not confounded by other determinants
      such as age, socioeconomic status, or parity. CONCLUSIONS: The prevalence of
      vitamin D deficiency in pregnant non-Western women in the Netherlands is very
      high, and screening should be recommended.

PMID- 16895883
TI  - Influence of high-carbohydrate mixed meals with different glycemic indexes on
      substrate utilization during subsequent exercise in women.
AB  - BACKGROUND: Few data exist on the metabolic responses to mixed meals with
      different glycemic indexes and their effects on substrate metabolism during
      exercise in women. OBJECTIVE: We examined the effects of preexercise mixed meals
      providing carbohydrates with high (HGI) or low glycemic index (LGI) on substrate
      utilization during rest and exercise in women. DESIGN: Eight healthy, active,
      eumenorrheic women [aged 18.6 +/- 0.9 y; body mass: 59.9 +/- 7.1 kg; maximal
      oxygen uptake (VO(2)max): 48.7 +/- 1.1 mL . kg(-1) . min(-1)] completed 2 trials.
      On each occasion, subjects were provided with a test breakfast 3 h before
      performing a 60-min run at 65% VO(2)max on a motorized treadmill. Both breakfasts
      provided 2 g carbohydrate/kg body mass and were isoenergetic. The calculated GIs
      of the meals were 78 (HGI) and 44 (LGI). RESULTS: Peak plasma glucose and serum
      insulin concentrations were greater after the HGI breakfast than after the LGI
      breakfast (P < 0.05). No significant differences in substrate oxidation were
      reported throughout the postprandial period. During exercise, the estimated rate
      of fat oxidation was greater in the LGI trial than in the HGI trial (P < 0.05).
      Similarly, plasma free fatty acid and glycerol concentrations were higher
      throughout exercise in the LGI trial (P < 0.05). No significant differences in
      plasma glucose or serum insulin were observed during exercise. CONCLUSION:
      Altering the GI of the carbohydrate within a meal significantly changes the
      postprandial hyperglycemic and hyperinsulinemic responses in women. A LGI
      preexercise meal resulted in a higher rate of fat oxidation during exercise than
      did an HGI meal.

PMID- 16895884
TI  - Effect of oral vitamin B-12 with or without folic acid on cognitive function in
      older people with mild vitamin B-12 deficiency: a randomized, placebo-controlled
      trial.
AB  - BACKGROUND: Vitamin B-12 deficiency is associated with cognitive impairment in
      older people. However, evidence from randomized trials of the effects of vitamin
      B-12 supplementation on cognitive function is limited and inconclusive.
      OBJECTIVE: The objective was to investigate whether daily supplementation with
      high doses of oral vitamin B-12 alone or in combination with folic acid has any
      beneficial effects on cognitive function in persons aged >/=70 y with mild
      vitamin B-12 deficiency. DESIGN: In a double-blind, placebo-controlled trial, 195
      subjects were randomly assigned to receive 1000 microg vitamin B-12, 1000 microg
      vitamin B-12 + 400 microg folic acid, or placebo for 24 wk. Vitamin B-12 status
      was assessed on the basis of methylmalonic acid, total homocysteine (tHcy), and
      holotranscobalamin (holoTC) concentrations before and after 12 and 24 wk of
      treatment. Cognitive function was assessed before and after 24 wk of treatment
      with the use of an extensive neuropsychologic test battery that included the
      domains of attention, construction, sensomotor speed, memory, and executive
      function. RESULTS: Vitamin B-12 status did not change significantly after
      treatment in the placebo group; however, oral vitamin B-12 supplementation
      corrected mild vitamin B-12 deficiency. Vitamin B-12 + folic acid supplementation
      increased red blood cell folate concentrations and decreased tHcy concentrations
      by 36%. Improvement in memory function was greater in the placebo group than in
      the group who received vitamin B-12 alone (P = 0.0036). Neither supplementation
      with vitamin B-12 alone nor that in combination with folic acid was accompanied
      by any improvement in other cognitive domains. CONCLUSION: Oral supplementation
      with vitamin B-12 alone or in combination with folic acid for 24 wk does not
      improve cognitive function.

PMID- 16895885
TI  - Absorbability and utility of calcium in mineral waters.
AB  - BACKGROUND: Calcium intake in North America remains substantially below
      recommended amounts. Bottled waters high in calcium could help close that gap.
      OBJECTIVES: The objectives were to summarize and integrate published
      absorbability and biodynamic data concerning high-calcium mineral waters and to
      combine these data with hitherto unpublished analyses from my laboratory. DESIGN:
      The usual library database was searched. The absorbability of calcium from a high
      mineral water labeled with tracer quantities of (45)Ca was measured in human
      volunteers as a part of an otherwise low-calcium test meal. Published reports
      that used differing load sizes and meal conditions were harmonized by making
      corrections based on published calcium absorbability data. RESULTS: All the high
      calcium mineral waters had absorbabilities equal to milk calcium or slightly
      better. When tested, all produced biodynamic responses indicative of absorption
      of appreciable quantities of calcium (ie, increased urinary calcium, decreased
      serum parathyroid hormone, decreased bone resorption biomarkers, and protection
      of bone mass). CONCLUSION: High-calcium mineral waters could provide useful
      quantities of bioavailable calcium.

PMID- 16895886
TI  - Distribution of serum concentrations of alpha-tocopherol and gamma-tocopherol in
      the US population.
AB  - BACKGROUND: Although the population distribution of serum concentrations of alpha
      tocopherol has been described in the United States, little is known about the
      distribution of gamma-tocopherol or the ratio of alpha-tocopherol to gamma
      tocopherol. OBJECTIVE: Our aim was to describe the distribution of serum
      concentrations of alpha-tocopherol and gamma-tocopherol in a nationally
      representative sample of US adults. DESIGN: We reviewed data from 4087 adults
      aged >/=20 y who participated in the National Health and Nutrition Examination
      Survey (1999-2000). Concentrations of alpha-tocopherol and gamma-tocopherol were
      measured by using HPLC with ultraviolet-visible wavelength detection. RESULTS:
      The arithmetic mean (+/-SEM) of serum concentrations of alpha-tocopherol was
      30.09 +/- 0.45 micromol/L, the median was 25.94 micromol/L, and the geometric
      mean (+/-SEM) was 27.39 +/- 0.38 micromol/L. The arithmetic mean of serum
      concentrations of gamma-tocopherol was 5.74 +/- 0.22 micromol/L, the median was
      5.25 micromol/L, and the geometric mean was 4.79 +/- 0.18 micromol/L. The median
      ratio of alpha-tocopherol to total cholesterol was 4.93 micromol/mmol, that of
      gamma-tocopherol to total cholesterol was 1.03 micromol/mmol, and that of alpha
      tocopherol to gamma-tocopherol was 4.53 micromol/mmol. Concentrations of alpha
      tocopherol increased significantly (P for trend < 0.001) with age and were
      significantly (P = 0.015) lower in men than in women. African Americans and
      Mexican Americans had significantly (P < 0.001) lower concentrations of alpha
      tocopherol than did whites. The median concentrations of gamma-tocopherol showed
      a trend with respect to age, did not differ significantly between men and women,
      and were slightly but nonsignificantly lower in white participants than in
      African American or Mexican American participants. CONCLUSION: Sociodemographic
      variations in serum concentrations of alpha-tocopherol and gamma-tocopherol exist
      among US adults.

PMID- 16895888
TI  - Major variables of zinc homeostasis in Chinese toddlers.
AB  - BACKGROUND: Measurement of the major variables of zinc homeostasis is an
      essential prerequisite for estimating human zinc requirements, which currently
      require a factorial approach. The data required for this approach have not been
      available for toddlers, whose requirements have been estimated by extrapolation
      from other age groups. OBJECTIVE: The objective of the study was to measure key
      variables of zinc homeostasis in rural and small-town Chinese toddlers. DESIGN:
      Zinc stable-isotope tracers were administered intravenously and orally with all
      meals for 1 d to 43 toddlers. Subsequent metabolic collections in the homes
      included duplicate diets, quantitative fecal collections, and spot urine
      sampling. Fractional absorption of zinc (FAZ) was measured by a dual-isotope
      tracer ratio technique, and endogenous fecal zinc (EFZ) was measured by an
      isotope dilution technique. RESULTS: No group or sex differences were found.
      Therefore, results were combined for 43 toddlers aged 19-25 mo whose major food
      staple was white rice. Selected results (x+/- SD) were 1.86 +/- 0.55 mg total
      dietary Zn/d; 0.35 +/- 0.12 FAZ; 0.63 +/- 0.24 mg total absorbed Zn/d; 0.67 +/-
      0.23 mg EFZ/d; and 65.0 +/- 8.3 microg plasma Zn/dL. The molar ratio of dietary
      phytate to zinc was 2.7:1. CONCLUSIONS: The mean intake and absorption of zinc in
      this population are low in comparison with estimated average dietary and
      physiologic requirements for zinc, and plasma zinc values are consistent with
      zinc deficiency. Intestinal losses of endogenous zinc exceed previous estimates
      for toddlers, and only modest evidence exists of conservation in response to low
      zinc intake and absorption.

PMID- 16895887
TI  - Lymphocyte propionyl-CoA carboxylase and its activation by biotin are sensitive
      indicators of marginal biotin deficiency in humans.
AB  - BACKGROUND: Marginal biotin deficiency may be a human teratogen. A biotin status
      indicator that is not dependent on renal function may be useful in studies of
      biotin status during pregnancy. A previous study of experimental biotin
      deficiency suggested that propionyl-coenzyme A carboxylase (PCC) activity in
      peripheral blood lymphocytes (PBLs) is a sensitive indicator of biotin status.
      OBJECTIVE: We examined the utility of measuring PCC activity and the activation
      of PCC by biotin in detecting marginal biotin deficiency. DESIGN: Marginal biotin
      deficiency was induced in 7 adults (3 women) by egg-white feeding for 28 d. Blood
      and urine were obtained on days 0, 14, and 28 (depletion phase) and 44 and 65
      (repletion phase). PBLs were incubated with (activated) or without (control)
      biotin before PCC assay. The activation coefficient of PCC is the ratio of PCC
      activity in activated PBLs to that in control PBLs. The significance of
      differences for all measurements was tested by repeated-measures analysis of
      variance with Fisher's post hoc test and Bonferroni correction. RESULTS: Changes
      in the urinary excretion of biotin and of 3-hydroxyisovaleric acid confirmed that
      marginal biotin deficiency was successfully induced. By day 14, PCC activity had
      decreased (P < 0.0001) to below the lower limit of normal in all subjects. By day
      28, the activation coefficient of PCC had increased significantly (P = 0.003) and
      was above the upper limit of normal in 6 of 7 subjects. CONCLUSION: PCC activity
      is the most sensitive indicator of biotin status tested to date. In future
      pregnancy studies, the use of lymphocyte PCC activity data should prove valuable
      in the assessment of biotin status.

PMID- 16895889
TI  - Antioxidant supplementation does not affect fasting plasma glucose in the
      Supplementation with Antioxidant Vitamins and Minerals (SU.VI.MAX) study in
      France: association with dietary intake and plasma concentrations.
AB  - BACKGROUND: Observational data suggest a protective effect of several
      antioxidants on fasting plasma glucose (FPG) and type 2 diabetes. However,
      randomized trials have yielded inconsistent results. OBJECTIVES: The first
      objective was to assess the effect of 7.5 y of antioxidant supplementation on FPG
      at 7.5 y. The second objective was to examine the epidemiologic association of
      baseline dietary intakes or plasma antioxidants and FPG (at baseline and at 7.5
      y). DESIGN: Subjects (n = 3146) from the Supplementation en Vitamines et Mineraux
      Antioxydants (SU.VI.MAX) primary prevention trial in France were randomly
      assigned to receive a daily capsule containing 120 mg vitamin C, 30 mg vitamin E,
      6 mg beta-carotene, 100 mug Se, and 20 mg Zn or a placebo. RESULTS: After 7.5 y,
      no significant difference was observed between age-adjusted mean FPG in men (P =
      0.78) and women (P = 0.89) in either group. Baseline beta-carotene dietary
      intakes and plasma concentrations were inversely associated with FPG in
      multivariate mixed models (P = 0.0045 and P < 0.0001, respectively). Baseline
      plasma vitamin C and selenium were negatively (P = 0.0455) and positively (P <
      0.0001) associated, respectively, with FPG. CONCLUSIONS: Supplementation with
      antioxidants at nutritional doses for 7.5 y had no effect on FPG in men or women
      who followed a balanced diet. An inverse association of baseline beta-carotene
      dietary intake and plasma concentrations with FPG was found, probably because
      beta-carotene is an indirect marker of fruit and vegetable intakes.

PMID- 16895890
TI  - Intakes of 4 dietary lignans and cause-specific and all-cause mortality in the
      Zutphen Elderly Study.
AB  - BACKGROUND: Plant lignans are converted to enterolignans that have antioxidant
      and weak estrogen-like activities, and therefore they may lower cardiovascular
      disease and cancer risks. OBJECTIVE: We investigated whether the intakes of 4
      plant lignans (lariciresinol, pinoresinol, secoisolariciresinol, and
      matairesinol) were inversely associated with coronary heart disease (CHD),
      cardiovascular diseases (CVD), cancer, and all-cause mortality. DESIGN: The
      Zutphen Elderly Study is a prospective cohort study in which 570 men aged 64-84 y
      were followed for 15 y. We recently developed a database and used it to estimate
      the dietary intakes of 4 plant lignans. Lignan intake was related to mortality
      with the use of Cox proportional hazards analysis. RESULTS: The median total
      lignan intake in 1985 was 977 microg/d. Tea, vegetables, bread, coffee, fruit,
      and wine were the major sources of lignan. The total lignan intake was not
      related to mortality. However, the intake of matairesinol was inversely
      associated with CHD, CVD, and all-cause mortality (P </= 0.05 for all) and cancer
      (P = 0.06). Multivariate-adjusted rate ratios (95% CI) per 1-SD increase in
      intake were 0.72 (0.53, 0.98) for CHD, 0.83 (0.69, 1.00) for CVD, 0.86 (0.76,
      0.97) for all-cause mortality, and 0.81 (0.65, 1.00) for cancer. CONCLUSIONS:
      Total lignan intake was not associated with mortality. The intake of matairesinol
      was inversely associated with mortality due to CHD, CVD, cancer, and all causes.
      We cannot exclude the possibility that the inverse association between
      matairesinol intake and mortality is due to an associated factor, such as wine
      consumption.

PMID- 16895891
TI  - Isoflavones in breastfed infants after mothers consume soy.
AB  - BACKGROUND: The bioavailability of isoflavones in children after soy exposure is
      uncertain. OBJECTIVE: We aimed to compare isoflavone patterns in infants exposed
      to isoflavone-containing breast milk (BF), in tofu-fed (TF) infants, and in
      mothers consuming a soy beverage. DESIGN: Eighteen nursing mothers who were not
      feeding soy foods to their infants consumed one daily serving of a soy protein
      beverage for 2-4 d and collected their own milk and urine and infant urine.
      Plasma was collected from infants if venous blood draws were ordered by
      pediatricians. Blood and urine were collected from additional children after they
      consumed tofu. Isoflavones were measured by liquid chromatography-mass
      spectrometry. RESULTS: In 7 subjects, isoflavone values increased significantly
      from baseline after mothers ate soy: in maternal urine (x +/- SEM) from 18.4 +/-
      13.0 to 135.1 +/- 26.0 nmol/mg creatinine, in breast milk from 5.1 +/- 2.2 to
      70.7 +/- 19.2 nmol/L, and in infant urine from 29.8 +/- 11.6 to 111.6 +/- 18.9
      nmol/mg creatinine. The mean isoflavone concentration in plasma obtained from 11
      BF infants was 19.7 +/- 13.2 nmol/L. TF infants had much higher mean isoflavone
      values (urine, 229 +/- 129 nmol/mg creatinine; plasma, 1049 +/- 403 nmol/L).
      Statistically significant correlations were observed between the types of fluids
      investigated within mothers, between mothers and infants, and within infants.
      Urinary isoflavone excretion per hour adjusted for dose per body weight was 81%
      lower for BF infants and 24% higher for TF infants than for their mothers after
      eating soy. CONCLUSIONS: More isoflavones appear in children than in adults after
      adjustment for isoflavone intake. Systemic isoflavone exposure in infants can be
      determined by urinary analysis.

PMID- 16895892
TI  - Calcium retention in adolescent boys on a range of controlled calcium intakes.
AB  - BACKGROUND: National calcium requirements in the United States for boys are based
      on data from girls. On average, boys develop larger skeletons than do girls, yet
      it is unknown whether the additional skeletal accretion in boys requires
      additional dietary calcium intake. OBJECTIVE: The objective was to determine
      calcium retention in adolescent boys in response to a range of controlled intakes
      and to compare the intake needed for maximal retention in boys with that needed
      in adolescent girls studied under the same conditions. DESIGN: Thirty-one boys
      aged 12-15 y participated in 3-wk metabolic balance studies testing a range (700
      2100 mg/d) of calcium intakes in a crossover study design with a 2-wk washout
      period. Calcium intake was varied by using a beverage fortified with calcium
      citrate malate. After a 1-wk equilibration period, calcium retention was
      calculated as dietary calcium intake minus the calcium excreted in the feces and
      urine over the following 2 wk. The dietary intake at which maximal calcium
      retention occurred was determined by using a nonlinear regression model. The
      results in boys were compared with those obtained in 35 adolescent girls
      previously studied under the same protocol. RESULTS: Maximal calcium retention in
      boys was achieved at an intake of 1140 mg/d. Calcium retention was higher (by 171
      +/- 38 mg/d) in boys than in girls at all calcium intakes studied. CONCLUSION:
      The higher calcium retention in boys than in girls was attained through higher
      net calcium absorption and lower urinary excretion than in girls.

PMID- 16895894
TI  - Body mass index history and risk of type 2 diabetes: results from the European
      Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study.
AB  - BACKGROUND: Obesity and increases in body weight in adults are considered to be
      among the most important risk factors for type 2 diabetes. OBJECTIVE: The
      objective was to evaluate and compare the associations between weight changes
      during 2 different periods of adult life and the risk of type 2 diabetes and age
      at diagnosis. DESIGN: The study included 7720 men and 10 371 women from the
      European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study
      with information on weight history; 390 men and 303 women of these participants
      received a clinical diagnosis of type 2 diabetes during 7 y of follow-up.
      Multivariate Cox regression models were used to estimate the relative risk (RR)
      of weight changes between ages 25 and 40 y and ages 40 and 55 y. RESULTS: RR
      estimates in men and women were slightly higher for each unit of BMI gain between
      ages 25 and 40 y [men: 1.25 (95% CI: 1.21, 1.30); women: 1.24 (1.20, 1.27)] than
      between ages 40 and 55 y [men: 1.13 (1.10, 1.16); women: 1.11 (1.08, 1.14)].
      Severe weight gain between ages 25 and 40 y was associated with a higher diabetes
      risk in men (1.5 times) and in women (4.3 times) than were stable weight in early
      adulthood and weight gain in later life, and it resulted in an average lower age
      at diabetes diagnosis in men (5 y) and in women (3 y). CONCLUSION: Weight gain in
      early adulthood is related to a higher risk and earlier onset of type 2 diabetes
      than is weight gain between 40 and 55 y of age.

PMID- 16895893
TI  - Magnesium and muscle performance in older persons: the InCHIANTI study.
AB  - BACKGROUND: The role of magnesium in maintaining muscle integrity and function in
      older adults is largely unknown. OBJECTIVE: We aimed to investigate the relation
      between serum magnesium concentrations and muscle performance in older subjects.
      DESIGN: Data are from the baseline examination conducted between September 1998
      and March 2000 of the InCHIANTI (aging in the Chianti area) study, a prospective
      epidemiologic survey of risk factors for late-life disability. From among 1453
      randomly selected community residents completing a home interview, 1138 men (46%)
      and women (aged 66.7 +/- 15.2 y; x +/- SD) with complete data on muscle
      performance and serum magnesium who were not severely cognitively compromised and
      had no evidence of kidney disease or hypercalcemia were included in the analysis.
      Muscle performance was evaluated by grip strength, lower-leg muscle power, knee
      extension torque, and ankle extension isometric strength and was normalized for
      age and body mass index (BMI) within each sex. RESULTS: After adjustment for age,
      sex, BMI, laboratory variables, presence of chronic diseases, muscle area, muscle
      density, and physical activity level, serum magnesium concentrations were
      significantly associated with indexes of muscle performance, including grip
      strength (beta = 2.0 +/- 0.5, P = 0.0002), lower-leg muscle power (beta = 8.8 +/-
      2.7, P = 0.001), knee extension torque (beta = 31.2 +/- 7.9, P < 0.0001), and
      ankle extension strength (beta = 3.8 +/- 0.5, P < 0.0001). CONCLUSIONS: The serum
      magnesium concentration is an independent correlate of muscle performance in
      older persons. Whether magnesium supplementation improves muscle function remains
      to be shown.

PMID- 16895895
TI  - Nutritional risk and the metabolic syndrome in women: opportunities for
      preventive intervention from the Framingham Nutrition Study.
AB  - BACKGROUND: Diet is recognized as a key factor in the cause and management of the
      metabolic syndrome (MetS). However, policies to guide preventive clinical
      nutrition interventions of the condition are limited. OBJECTIVES: We examined the
      relation between dietary quality and incident MetS in adult women and identified
      foci for preventive nutrition interventions. DESIGN: This was a prospective study
      of 300 healthy women (aged 30-69 y) in the Framingham Offspring-Spouse study who
      were free of MetS risk factors at baseline. The development of individual MetS
      traits and overall MetS status during 12 y of follow-up were compared in women by
      tertile of nutritional risk, based on intake of 19 nutrients. Multivariate
      logistic regression models considered age, smoking, physical activity, and
      menopausal status. RESULTS: Baseline age-adjusted mean nutrient intake and
      ischemic heart disease risk profiles differed by tertile of nutritional risk.
      Women with higher nutritional risk profiles consumed more dietary lipids (total,
      saturated, and monounsaturated fats) and alcohol and less fiber and
      micronutrients; they had higher cigarette use and waist circumferences. Compared
      with women with the lowest nutritional risk, those in the highest tertile had a 2
      to 3-fold risk of the development of abdominal obesity and overall MetS during
      12 y of follow-up [odds ratio: 2.3 (95% CI: 1.2, 4.3) and 3.0 (95% CI: 1.2, 7.6),
      respectively]. CONCLUSIONS: Higher composite nutritional risk predicts the
      development of abdominal obesity and MetS during long-term follow-up in healthy
      women, independent of lifestyle and ischemic heart disease risk factors.
      Preventive nutrition interventions for obesity and MetS risk reduction should
      focus on the overall nutritional quality of women's dietary profiles.

PMID- 16895896
TI  - Factor analysis of fatty acids in serum lipids as a measure of dietary fat
      quality in relation to the metabolic syndrome in men.
AB  - BACKGROUND: A specific fatty acid (FA) composition in plasma lipid esters is
      related to the metabolic syndrome (MetS) and may influence the development of the
      MetS. OBJECTIVE: The objective was to define and study FA factors as measures of
      dietary fat quality and endogenous FA metabolism in relation to MetS. DESIGN:
      Principal factor analysis was performed to define specific FA factors in men
      participating in a population-based cohort study-the Uppsala Longitudinal Study
      of Adult Men. The factors were generated at ages 50 (n = 2009) and 70 (n = 576)
      y, and relations between FA factors and MetS (National Cholesterol Education
      Program) were studied in cross-sectional and prospective (20 y) analyses.
      RESULTS: The factor analysis generated 3 major FA factors: a low-linoleic acid
      (LA) factor, a dietary saturated FA factor, and an n-3 polyunsaturated FA (PUFA)
      factor. All factors differed between those subjects with MetS (n = 281 of 2009)
      and those without MetS at age 50 y; only the low-LA factor differed at age 70 y,
      which suggests an association between MetS and fat quality. The low-LA factor
      (odds ratio: 1.51; 95% CI: 1.28, 1.79; P < 0.0001) and the n-3 PUFA factor (0.76;
      0.64, 0.90; P < 0.001) predicted MetS development over 20 y, independent of
      smoking habits, physical activity, and BMI. CONCLUSIONS: The generated FA
      factors, which presumably represent dietary fat quality and endogenous FA
      metabolism, may be important in the development of MetS. This finding supports
      current dietary recommendations to increase PUFA intakes and restrict saturated
      FA intakes.

PMID- 16895897
TI  - Weight, shape, and mortality risk in older persons: elevated waist-hip ratio, not
      high body mass index, is associated with a greater risk of death.
AB  - BACKGROUND: Guidelines for optimal weight in older persons are limited by
      uncertainty about the ideal body mass index (BMI) or the usefulness of
      alternative anthropometric measures. OBJECTIVE: We investigated the association
      of BMI (in kg/m(2)), waist circumference, and waist-hip ratio (WHR) with
      mortality and cause-specific mortality. DESIGN: Subjects aged >/=75 y (n = 14
      833) from 53 family practices in the United Kingdom underwent a health assessment
      that included measurement of BMI and waist and hip circumferences; they also were
      followed up for mortality. RESULTS: During a median follow-up of 5.9 y, 6649
      subjects died (46% of circulatory causes). In nonsmoking men and women (90% of
      the cohort), compared with the lowest quintile of BMI (<23 in men and <22.3 in
      women), adjusted hazard ratios (HRs) for mortality were <1 for all other
      quintiles of BMI (P for trend = 0.0003 and 0.0001 in men and women,
      respectively). Increasing WHR was associated with increasing HRs in men and women
      (P for trend = 0.008 and 0.0002, respectively). BMI was not associated with
      circulatory mortality in men (P for trend = 0.667) and was negatively associated
      in women (P for trend = 0.004). WHR was positively related to circulatory
      mortality in both men and women (P for trend = 0.001 and 0.005, respectively).
      Waist circumference was not associated with all-cause or circulatory mortality.
      CONCLUSIONS: Current guidelines for BMI-based risk categories overestimate risks
      due to excess weight in persons aged >/=75 y. Increased mortality risk is more
      clearly indicated for relative abdominal obesity as measured by high WHR.

PMID- 16895898
TI  - The low fat paradox--do dietary carbohydrates increase circulating saturated
      fatty acids?

PMID- 16895899
TI  - The acute and chronic toxic effects of vitamin A.

PMID- 16895900
TI  - Deletion mutagenesis of p22phox subunit of flavocytochrome b558: identification
      of regions critical for gp91phox maturation and NADPH oxidase activity.
AB  - The heterodimeric flavocytochrome b558, comprised of the two integral membrane
      proteins p22phox and gp91phox, mediates the transfer of electrons from NADPH to
      molecular oxygen in the phagocyte NADPH oxidase to generate the superoxide
      precursor of microbicidal oxidants. This study uses deletion mutagenesis to
      identify regions of p22phox required for maturation of gp91phox and for NADPH
      oxidase activity. N-terminal, C-terminal, or internal deletions of human p22phox
      were generated and expressed in Chinese hamster ovary cells with transgenes for
      gp91phox and two other NADPH oxidase subunits, p47phox, and p67phox. The results
      demonstrate that p22phox-dependent maturation of gp91phox carbohydrate, cell
      surface expression of gp91phox, and the enzymatic function of flavocytochrome
      b558 are closely correlated. Whereas the 5 N-terminal and 25 C-terminal amino
      acids are dispensable for these functions, the N-terminal 11 amino acids of
      p22phox are required, as is a hydrophilic region between amino acids 65 and 90.
      Upon deletion of 54 residues at the C terminus of p22phox (amino acids 142-195),
      maturation and cell surface expression of gp91phox was still preserved, although
      NADPH oxidase activity was absent, as expected, due to removal of a proline-rich
      domain between amino acids 151-160 that is required for recruitment of p47phox.
      Antibody binding studies indicate that the extreme N terminus of p22phox is
      inaccessible in the absence of cell permeabilization, supporting a model in which
      both the N- and C-terminal domains of p22phox extend into the cytoplasm, anchored
      by two membrane-embedded regions.

PMID- 16895901
TI  - Cloning and characterization of the annexin II receptor on human marrow stromal
      cells.
AB  - Annexin II is a heterotetramer, consisting of two 11-kDa (p11) and two 36-kDa
      (p36) subunits, that is produced by osteoclasts and stimulates osteoclast
      formation. However, its receptor is unknown. We showed that annexin II binds to
      normal primary human marrow stromal cells and the Paget's marrow-derived PSV10
      stromal cell line to induce osteoclast formation. 125I-Labeled annexin II binding
      assays with PSV10 cells demonstrated that there was a single class of annexin II
      receptors with a Kd of 5.79 nm and Bmax of 2.13 x 10(5) receptors/cell. Annexin
      III or annexin V did not bind this receptor. Using 125I-labeled annexin II
      binding to screen NIH3T3 transfected with a human marrow cDNA expression library,
      we identified a putative annexin II receptor clone, which encoded a novel 26-kDa
      type I membrane receptor protein when expressed in HEK 293 cells. HEK 293 cells
      transformed with the cloned annexin II receptor cDNA showed a similar binding
      affinity to annexin II as that observed in PSV10 cells. Chemical cross-linking
      experiments with biotinylated annexin II and intact PSV10 cells identified a 55
      kDa band on Western blot analysis that reacted with both an anti-p11 antibody and
      streptavidin but not anti-p36 antibody. A rabbit polyclonal antibody raised
      against the putative recombinant annexin II receptor also recognized the same 26
      kDa protein band detected in PSV10 cells. Importantly, the annexin II receptor
      antibody dose-dependently blocked the stimulatory effects of annexin II on human
      osteoclast formation, demonstrating that the receptor mediates the effects of
      annexin II on osteoclast formation.

PMID- 16895902
TI  - Both cleavage products of the mCLCA3 protein are secreted soluble proteins.
AB  - Members of the chloride channels, calcium-activated (CLCA) family of proteins and
      in particular the murine mCLCA3 (alias gob-5) and its human ortholog hCLCA1 have
      been identified as clinically relevant molecules in diseases with secretory
      dysfunctions including asthma and cystic fibrosis. Initial studies have indicated
      that these proteins evoke a calcium-activated chloride conductance when
      transfected into human embryonic kidney cells 293 cells. However, it is not yet
      clear whether the CLCA proteins form chloride channels per se or function as
      mediators of other, yet unknown chloride channels. Here, we present a systematic
      biochemical analysis of the posttranslational processing and intracellular
      trafficking of the mCLCA3 protein. Pulse-chase experiments after metabolic
      protein labeling of mCLCA3-transfected COS-1 or human embryonic kidney 293 cells
      revealed cleavage of a primary 110-kDa mCLCA3 translation product in the
      endoplasmic reticulum into a 75-kDa amino-terminal and a 35-kDa carboxyl-terminal
      protein that were glycosylated and remained physically associated with each
      other. Confocal fluorescent analyses identified both cleavage products in
      vesicles of the secretory pathway. Neither cleavage product was associated with
      the cell membrane at any time. Instead, both subunits were fully secreted into
      the extracellular environment as a soluble complex of two glycoproteins. These
      results suggest that the two mCLCA3 cleavage products cannot form an anion
      channel on their own but may instead act as extracellular signaling molecules.
      Furthermore, our results point toward significant structural differences between
      mCLCA3 and its human ortholog, hCLCA1, which is thought to be a single, non
      integral membrane protein.

PMID- 16895903
TI  - Tracking and elucidating alphavirus-host protein interactions.
AB  - Viral infections cause profound alterations in host cells. Here, we explore the
      interactions between proteins of the Alphavirus Sindbis and host factors during
      the course of mammalian cell infection. Using a mutant virus expressing the viral
      nsP3 protein tagged with green fluorescent protein (GFP) we directly observed
      nsP3 localization and isolated nsP3-interacting proteins at various times after
      infection. These results revealed that host factor recruitment to nsP3-containing
      complexes was time dependent, with a specific early and persistent recruitment of
      G3BP and a later recruitment of 14-3-3 proteins. Expression of GFP-tagged G3BP
      allowed reciprocal isolation of nsP3 in Sindbis infected cells, as well as the
      identification of novel G3BP-interacting proteins in both uninfected and infected
      cells. Note-worthy interactions include nuclear pore complex components whose
      interactions with G3BP were reduced upon Sindbis infection. This suggests that
      G3BP is a nuclear transport factor, as hypothesized previously, and that viral
      infection may alter RNA transport. Immunoelectron microscopy showed that a
      portion of Sindbis nsP3 is localized at the nuclear envelope, suggesting a
      possible site of G3BP recruitment to nsP3-containing complexes. Our results
      demonstrate the utility of using a standard GFP tag to both track viral protein
      localization and elucidate specific viral-host interactions over time in infected
      mammalian cells.

PMID- 16895904
TI  - Loss of caspase-9 provides genetic evidence for the type I/II concept of CD95
      mediated apoptosis.
AB  - The death receptor CD95 triggers apoptosis upon formation of a death-inducing
      signaling complex and the activation of caspase-8. Two types of CD95-mediated
      apoptosis have been distinguished that differ in their efficiency of death
      inducing signaling complex formation and the requirement of mitochondria for
      caspase activation. The validity of the type I/II model, however, has been
      challenged, as Bcl-2 expression or the use of various CD95 agonists resulted in
      different apoptosis effects. By identifying a caspase-9-deficient T cell line, we
      now provide genetic evidence for the two-pathway model of CD95-mediated apoptosis
      and demonstrate that type II cells strongly depend on caspase-9. Caspase-9
      deficient cells revealed strongly impaired apoptosis, caspase activation, and
      mitochondrial membrane depolarization upon CD95 triggering, whereas,
      surprisingly, activation of Bak and cytochrome c release were not inhibited.
      Furthermore, caspase-9-deficient cells did not switch to necrosis, and
      reconstitution of caspase-9 expression restored CD95 sensitivity. Finally, we
      also show that different death receptors have a distinct requirement for caspase
      9.

PMID- 16895905
TI  - Identification of gamma-aminobutyric acid receptor-interacting factor 1 (TRAK2)
      as a trafficking factor for the K+ channel Kir2.1.
AB  - To identify proteins that regulate potassium channel activity and expression, we
      performed functional screening of mammalian cDNA libraries in yeast that express
      the mammalian K(+) channel Kir2.1. Growth of Kir2.1-expressing yeast in media
      with low K(+) concentration is a function of K(+) uptake via Kir2.1 channels.
      Therefore, the host strain was transformed with a human cDNA library, and cDNA
      clones that rescued growth at low K(+) concentration were selected. One of these
      clones was identical to the protein of unknown function isolated previously as
      gamma-aminobutyric acid receptor-interacting factor 1 (GRIF-1) (Beck, M.,
      Brickley, K., Wilkinson, H., Sharma, S., Smith, M., Chazot, P., Pollard, S., and
      Stephenson, F. (2002) J. Biol. Chem. 277, 30079-30090). GRIF-1 specifically
      enhanced Kir2.1-dependent growth in yeast and Kir2.1-mediated (86)Rb(+) efflux in
      HEK293 cells. Quantitative microscopy and flow cytometry analysis of
      immunolabeled surface Kir2.1 channel showed that GRIF-1 significantly increased
      the number of Kir2.1 channels in the plasma membrane of COS and HEK293 cells.
      Physical interaction of Kir2.1 channel and GRIF-1 was demonstrated by co
      immunoprecipitation from HEK293 lysates and yeast two-hybrid assay. In vivo
      association of Kir2.1 and GRIF-1 was demonstrated by co-immunoprecipitation from
      brain lysate. Yeast two-hybrid assays showed that an N-terminal region of GRIF-1
      interacts with a C-terminal region of Kir2.1. These results indicate that GRIF-1
      binds to Kir2.1 and facilitates trafficking of this channel to the cell surface.

PMID- 16895906
TI  - Siglec-7 undergoes a major conformational change when complexed with the
      alpha(2,8)-disialylganglioside GT1b.
AB  - The siglecs are a group of mammalian sialic acid binding receptors expressed
      predominantly in the immune system. The CD33-related siglecs show complex
      recognition patterns for sialylated glycans. Siglec-7 shows a preference for
      alpha(2,8)-disialylated ligands and provides a structural template for studying
      the key interactions that drive this selectivity. We have co-crystallized Siglec
      7 with a synthetic oligosaccharide corresponding to the alpha(2,8)-disialylated
      ganglioside GT1b. The crystal structure of the complex offers a first glimpse
      into how this important family of lectins binds the structurally diverse
      gangliosides. The structure reveals that the C-C' loop, a region implicated in
      previous studies as driving siglec specificity, undergoes a dramatic
      conformational shift, allowing it to interact with the underlying neutral glycan
      core of the ganglioside. The structural data in combination with mutagenesis
      studies show that binding of the ganglioside is driven by extensive hydrophobic
      contacts together with key polar interactions and that the binding site structure
      is complementary to preferred solution conformations of GT1b.

PMID- 16895907
TI  - The alpha4 regulatory subunit exerts opposing allosteric effects on protein
      phosphatases PP6 and PP2A.
AB  - The protein Ser/Thr phosphatase family contains three enzymes called PP2A, PP4,
      and PP6 with separate biological functions inferred from genetics of the yeast
      homologues Pph21/22, Pph3, and Sit4. These catalytic subunits associate with a
      common subunit called alpha4 (related to yeast Tap42). Here, we characterized
      recombinant PP6 and PP2A catalytic monomers and alpha4.phosphatase heterodimers.
      Monomeric PP6 and PP2A showed identical kinetics using either p-nitrophenyl
      phosphate (pNPP) or 32P-myelin basic protein (MBP) as substrates, with matching
      Km and Vmax values. Using pNPP as substrate, PP6 and PP2A gave the same IC50 with
      active site inhibitors okadaic acid, microcystin-LR, calyculin A, and
      cantharidin. However, with MBP as substrate, PP6 was inhibited at 5-fold lower
      concentrations of toxins relative to PP2A, suggesting PP6 might be a preferred in
      vivo target of toxins. Heterodimeric alpha4.PP6 and alpha4.PP2A were starkly
      different. With MBP as substrate the alpha4.PP2A heterodimer had a 100-fold
      higher Vmax than alpha4.PP6, and neither heterodimer was active with pNPP. Thus,
      these phosphatases are distinguished by their different responses to allosteric
      binding of the common regulatory subunit alpha4. Transient expression of alpha4
      differentially increased or decreased phosphorylation of endogenous
      phosphoproteins, consistent with opposing effects on PP2A and PP6.

PMID- 16895908
TI  - RGS2 inhibits the epithelial Ca2+ channel TRPV6.
AB  - The epithelial Ca(2+) channels TRPV5 and TRPV6 constitute the apical Ca(2+) entry
      pathway in the process of active Ca(2+) (re)absorption. By yeast two-hybrid and
      glutathione S-transferase pulldown analysis we identified RGS2 as a novel TRPV6
      associated protein. RGS proteins determine the inactivation kinetics of
      heterotrimeric G-protein-coupled receptor (GPCR) signaling by regulating the
      GTPase activity of G(alpha) subunits. Here we demonstrate that TRPV6 interacts
      with the NH(2)-terminal domain of RGS2 in a Ca(2+)-independent fashion and that
      overexpression of RGS2 reduces the Na(+) and Ca(2+) current of TRPV6 but not that
      of TRPV5-transfected human embryonic kidney 293 (HEK293) cells. In contrast,
      overexpression of the deletion mutant DeltaN-RGS2, lacking the NH(2)-terminal
      domain of RGS2, in TRPV6-expressing HEK293 cells did not show this inhibition.
      Furthermore, cell surface biotinylation indicated that the inhibitory effect of
      RGS2 on TRPV6 activity is not mediated by differences in trafficking or retrieval
      of TRPV6 from the plasma membrane. This effect probably results from the direct
      interaction between RGS2 and TRPV6, affecting the gating properties of the
      channel. Finally, the scaffolding protein spinophilin, shown to recruit RGS2 and
      regulate GPCR-signaling via G(alpha), did not affect RGS2 binding and
      electrophysiological properties of TRPV6, indicating a GPCR-independent mechanism
      of TRPV6 regulation by RGS2.

PMID- 16895909
TI  - Examination of key intermediates in the catalytic cycle of aspartate-beta
      semialdehyde dehydrogenase from a gram-positive infectious bacteria.
AB  - Aspartate-beta-semialdehyde dehydrogenase (ASADH) catalyzes a critical branch
      point transformation in amino acid bio-synthesis. The products of the aspartate
      pathway are essential in microorganisms, and this entire pathway is absent in
      mammals, making this enzyme an attractive target for antibiotic development. The
      first structure of an ASADH from a Gram-positive bacterium, Streptococcus
      pneumoniae, has now been determined. The overall structure of the apoenzyme has a
      similar fold to those of the Gram-negative and archaeal ASADHs but contains some
      interesting structural variations that can be exploited for inhibitor design.
      Binding of the coenzyme NADP, as well as a truncated nucleotide analogue, into an
      alternative conformation from that observed in Gram-negative ASADHs causes an
      enzyme domain closure that precedes catalysis. The covalent acyl-enzyme
      intermediate was trapped by soaking the substrate into crystals of the coenzyme
      complex, and the structure of this elusive intermediate provides detailed
      insights into the catalytic mechanism.

PMID- 16895910
TI  - Renin enhancer is critical for control of renin gene expression and
      cardiovascular function.
AB  - The important cardiovascular regulator renin contains a strong in vitro enhancer
      2.7 kb upstream of its gene. Here we tested the in vivo role of the mouse Ren-1c
      enhancer. In renin-expressing As4.1 cells stably transfected with Ren-1c promoter
      with or without enhancer, expression of linked beta-geo reporter, stable
      expression, and colony formation were dependent on the presence of the enhancer.
      We then generated mice carrying a targeted deletion of the enhancer (REKO mice)
      and found marked depletion of renin in renal juxtaglomerular and submandibular
      ductal cells, as well as hyperplasia of macula densa cells. Plasma creatinine was
      increased, but electrolytes were normal. Male REKO mice implanted with telemetry
      devices had 9 +/- 1 mm Hg lower mean arterial pressure (p < 0.001), which was
      partly normalized by a high NaCl diet. Locomotor activity was lower, and
      baroreflex sensitivity was normal. Markedly reduced mean arterial pressure
      variability in the midfrequency band indicated a contribution of reduced
      sympathetic vasomotor tone to the hypotension. In conclusion, the renin enhancer
      is critical for renin gene expression and physiological sequelae, including
      response to alteration in salt intake. The REKO mouse may be useful as a low
      renin expression model.

PMID- 16895911
TI  - Efficient trafficking of ceramide from the endoplasmic reticulum to the Golgi
      apparatus requires a VAMP-associated protein-interacting FFAT motif of CERT.
AB  - Ceramide is synthesized at the endoplasmic reticulum (ER) and transported to the
      Golgi apparatus by CERT for its conversion to sphingomyelin in mammalian cells.
      CERT has a pleck-strin homology (PH) domain for Golgi targeting and a START
      domain catalyzing the intermembrane transfer of ceramide. The region between the
      two domains contains a short peptide motif designated FFAT, which is supposed to
      interact with the ER-resident proteins VAP-A and VAP-B. Both VAPs were actually
      co-immunoprecipitated with CERT, and the CERT/VAP interaction was abolished by
      mutations in the FFAT motif. These mutations did not affect the Golgi targeting
      activity of CERT. Whereas mutations of neither the FFAT motif nor the PH domain
      inhibited the ceramide transfer activity of CERT in a cell-free system, they
      impaired the ER-to-Golgi transport of ceramide in intact and in semi-intact cells
      at near endogenous expression levels. By contrast, when overexpressed, both the
      FFAT motif and the PH domain mutants of CERT substantially supported the
      transport of ceramide from the ER to the site where sphingomyelin is produced.
      These results suggest that the Golgi-targeting PH domain and ER-interacting FFAT
      motif of CERT spatially restrict the random ceramide transfer activity of the
      START domain in cells.

PMID- 16895912
TI  - A dedicated phosphopantetheinyl transferase for the fredericamycin polyketide
      synthase from Streptomyces griseus.
AB  - Polyketide synthases cannot be functional unless their apo-acyl carrier proteins
      (apo-ACPs) are post-translationally modified by covalent attachment of the 4'
      phosphopantetheine group to the highly conserved serine residue, and this
      reaction is catalyzed by phosphopantetheinyl transferases (PPTases). Cloning and
      sequence analysis of the 33-kb fredericamycin (FDM) biosynthetic gene cluster
      from Streptomyces griseus revealed fdmW, whose deduced gene product showed
      significant sequence homology to known PPTases. Biochemical characterization of
      FdmW in vitro confirmed that it is a PPTase. Inactivation of fdmW resulted in
      approximately 93% reduction of FDM production, and complementation of the
      fdmW::aac (3)IV mutant by expressing fdmW in trans restored FDM production to a
      level comparable with that of the wild-type strain. Although FdmW can
      phosphopantetheinylate various ACPs, it prefers its cognate substrate, the FdmH
      ACP, with a K(m) of 5.8 microM and a k(cat)/K(m) of 8.1 microM(-1) x min(-1), to
      heterologous ACPs, such as the TcmM ACP with a K(m) of 1.0 x 10(2) microM and a
      k(cat) /K(m) of 0.6 microM(-1) x min(-1). These findings suggest that FdmW is
      specific for FDM biosynthesis. FdmW therefore represents the first holo-ACP
      synthase-type PPTase identified from an aromatic polyketide biosynthetic gene
      cluster.

PMID- 16895913
TI  - Essential role of protein kinase C delta in platelet signaling, alpha IIb beta 3
      activation, and thromboxane A2 release.
AB  - The protein kinase C (PKC) family is an essential signaling mediator in platelet
      activation and aggregation. However, the relative importance of the major
      platelet PKC isoforms and their downstream effectors in platelet signaling and
      function remain unclear. Using isolated human platelets, we report that PKCdelta,
      but not PKCalpha or PKCbeta, is required for collagen-induced phospholipase C
      dependent signaling, activation of alpha(IIb)beta(3), and platelet aggregation.
      Analysis of PKCdelta phosphorylation and translocation to the membrane following
      activation by both collagen and thrombin indicates that it is positively
      regulated by alpha(IIb)beta(3) outside-in signaling. Moreover, PKCdelta triggers
      activation of the mitogen-activated protein kinase-kinase (MEK)/extracellular
      signal regulated kinase (ERK) and the p38 MAPK signaling. This leads to the
      subsequent release of thromboxane A(2), which is essential for collagen-induced
      but not thrombin-induced platelet activation and aggregation. This study adds new
      insight to the role of PKCs in platelet function, where PKCdelta signaling, via
      the MEK/ERK and p38 MAPK pathways, is required for the secretion of thromboxane
      A(2).

PMID- 16895914
TI  - Structural analysis of the regulatory dithiol-containing domain of the
      chloroplast ATP synthase gamma subunit.
AB  - The gamma subunit of the F1 portion of the chloroplast ATP synthase contains a
      critically placed dithiol that provides a redox switch converting the enzyme from
      a latent to an active ATPase. The switch prevents depletion of intracellular ATP
      pools in the dark when photophosphorylation is inactive. The dithiol is located
      in a special regulatory segment of about 40 amino acids that is absent from the
      gamma subunits of the eubacterial and mitochondrial enzymes. Site-directed
      mutagenesis was used to probe the relationship between the structure of the gamma
      regulatory segment and its function in ATPase regulation via its interaction with
      the inhibitory epsilon subunit. Mutations were designed using a homology model of
      the chloroplast gamma subunit based on the analogous structures of the bacterial
      and mitochondrial homologues. The mutations included (a) substituting both of the
      disulfide-forming cysteines (Cys199 and Cys205) for alanines, (b) deleting nine
      residues containing the dithiol, (c) deleting the region distal to the dithiol
      (residues 224-240), and (d) deleting the entire segment between residues 196 and
      241 with the exception of a small spacer element, and (e) deleting pieces from a
      small loop segment predicted by the model to interact with the dithiol domain.
      Deletions within the dithiol domain and within parts of the loop segment resulted
      in loss of redox control of the ATPase activity of the F1 enzyme. Deleting the
      distal segment, the whole regulatory domain, or parts of the loop segment had the
      additional effect of reducing the maximum extent of inhibition obtained upon
      adding the epsilon subunit but did not abolish epsilon binding. The results
      suggest a mechanism by which the gamma and epsilon subunits interact with each
      other to induce the latent state of the enzyme.

PMID- 16895915
TI  - Nuclear export of S6K1 II is regulated by protein kinase CK2 phosphorylation at
      Ser-17.
AB  - Ribosomal S6 kinases (S6Ks) are principal players in the regulation of cell
      growth and energy metabolism. Signaling via phosphatidylinositol 3-kinase and
      mammalian target of rapamycin pathways mediates the activation of S6K in response
      to various mitogenic stimuli. The family of S6Ks consists of two forms, S6K1 and 
      2, that have cytoplasmic and nuclear splicing variants, S6K1 II and S6K1 I,
      respectively. Nuclear-cytoplasmic shuttling of both isoforms induced by mitogenic
      stimuli has been reported recently. Here we present the identification of protein
      kinase CK2 (CK2) as a novel binding and regulatory partner for S6K1 II. The
      interaction between S6K1 II and CK2beta regulatory subunit was initially
      identified in a yeast two-hybrid screen and further confirmed by co
      immunoprecipitation of transiently expressed and endogenous proteins. The
      interaction between S6K1 II and CK2 was found to occur in serum-starved and serum
      stimulated cells. In addition, we found that S6K1 II is a substrate for CK2. The
      localization of the CK2 phosphorylation site was narrowed down to Ser-17 in S6K1
      II. Mutational analysis and the use of phosphospecific antibody indicate that Ser
      17 is a major in vitro and in vivo phosphorylation site for CK2. Functional
      studies reveal that, in contrast to the wild type kinase, the phosphorylation
      mimicking mutant of S6K1 II (S17E) retains its cytoplasmic localization in serum
      stimulated cells. Treatment of cells with the nuclear export inhibitor leptomycin
      B revealed that the S17E mutant accumulates in the nucleus to the same extent as
      S6K1 II wild type. These results indicate that nuclear import of the S17E mutant
      is not affected, although the export is significantly enhanced. We also provide
      evidence that nuclear export of S6K1 is mediated by a CRM1-dependent mechanism.
      Taken together, this study establishes a functional link between S6K1 II and CK2
      signaling, which involves the regulation of S6K1 II nuclear export by CK2
      mediated phosphorylation of Ser-17.

PMID- 16895916
TI  - Phospholipase C epsilon suppresses integrin activation.
AB  - Phospholipase Cepsilon (PLCepsilon) is a newly described effector of the small
      GTP-binding protein H-Ras. Utilizing H-Ras effector mutants, we show that mutants
      H-Ras(G12V/E37G) and H-Ras(G12V/D38N) suppressed integrin activation in an ERK
      independent manner. H-Ras(G12V/D38N) specifically activated the PLCepsilon
      effector pathway and suppressed integrin activation. Inhibition of PLCepsilon
      activation with a kinase-dead PLCepsilon mutant prevented H-Ras(G12V/D38N) from
      suppressing integrin activation, and low level expression of H-Ras(G12V/D38N)
      could synergize with wild-type PLCepsilon to suppress integrins. In addition,
      knockdown of endogenous PLCepsilon with small interfering RNA blocked H
      Ras(G12V/D38N)-mediated integrin suppression. Suppressing integrin function with
      the H-Ras(G12V/D38N) mutant reduced cell adhesion to von Willebrand factor and
      fibronectin; this reduction in cell adhesion was blocked by coexpression of the
      kinase-dead PLCepsilon mutant. These results show that H-Ras suppresses integrin
      affinity via independent Raf and PLCepsilon signaling pathways and demonstrate a
      new physiological function for PLCepsilon in the regulation of integrin
      activation.

PMID- 16895917
TI  - The last 10 amino acid residues beyond the hydrophobic motif are critical for the
      catalytic competence and function of protein kinase Calpha.
AB  - The segment C-terminal to the hydrophobic motif at the V5 domain of protein
      kinase C (PKC) is the least conserved both in length and in amino acid identity
      among all PKC isozymes. By generating serial truncation mutants followed by
      biochemical and functional analyses, we show here that the very C terminus of
      PKCalpha is critical in conferring the full catalytic competence to the kinase
      and for transducing signals in cells. Deletion of one C-terminal amino acid
      residue caused the loss of approximately 60% of the catalytic activity of the
      mutant PKCalpha, whereas deletion of 10 C-terminal amino acid residues abrogated
      the catalytic activity of PKCalpha in immune complex kinase assays. The PKCalpha
      C-terminal truncation mutants were found to lose their ability to activate
      mitogen-activated protein kinase, to rescue apoptosis induced by the inhibition
      of endogenous PKC in COS cells, and to augment melatonin-stimulated neurite
      outgrowth. Furthermore, molecular dynamics simulations revealed that the deletion
      of 1 or 10 C-terminal residues results in the deformation of the V5 domain and
      the ATP-binding pocket, respectively. Finally, PKCalpha immunoprecipitated using
      an antibody against its C terminus had only marginal catalytic activity compared
      with that of the PKCalpha immunoprecipitated by an antibody against its N
      terminus. Therefore, the very C-terminal tail of PKCalpha is a novel determinant
      of the catalytic activity of PKC and a promising target for selective modulation
      of PKCalpha function. Molecules that bind preferentially to the very C terminus
      of distinct PKC isozymes and suppress their catalytic activity may constitute a
      new class of selective inhibitors of PKC.

PMID- 16895918
TI  - Binding of myotrophin/V-1 to actin-capping protein: implications for how capping
      protein binds to the filament barbed end.
AB  - The heterodimeric actin-capping protein (CP) regulates actin assembly and cell
      motility by binding tightly to the barbed end of the actin filament. Here we
      demonstrate that myotrophin/V-1 binds directly to CP in a 1:1 molar ratio with a
      Kd of 10-50 nm. V-1 binding inhibited the ability of CP to cap the barbed ends of
      actin filaments. The actin-binding COOH-terminal region, the "tentacle," of the
      CP beta subunit was important for binding V-1, with lesser contributions from the
      alpha subunit COOH-terminal region and the body of the protein. V-1 appears to be
      unable to bind to CP that is on the barbed end, based on the observations that V
      1 had no activity in an uncapping assay and that the V-1.CP complex had no
      capping activity. Two loops of V-1, which extend out from the alpha-helical
      backbone of this ankyrin repeat protein, were necessary for V-1 to bind CP.
      Parallel computational studies determined a bound conformation of the beta
      tentacle with V-1 that is consistent with these findings, and they offered
      insight into experimentally observed differences between the alpha1 and alpha2
      isoforms as well as the mutant lacking the alpha tentacle. These results support
      and extend our "wobble" model for CP binding to the actin filament, in which the
      two COOH-terminal regions of CP bind independently to the actin filament, and
      bound CP is able to wobble when attached only via its mobile beta-subunit
      tentacle. This model is also supported by molecular dynamics simulations of CP
      reported here. The existence of the wobble state may be important for actin
      dynamics in cells.

PMID- 16895919
TI  - CFBP is a novel tyrosine-phosphorylated protein that might function as a
      regulator of CIN85/CD2AP.
AB  - To decipher the global network of the epidermal growth factor (EGF) receptor
      mediated signaling pathway, a large scale proteomic analysis of tyrosine
      phosphorylated proteins was conducted. Here, we focus on characterizing a novel
      protein, CFBP (CIN85/CD2AP family binding protein), identified in the study. CFBP
      was found to be phosphorylated at tyrosine 204 upon EGF stimulation, and the
      CIN85/CD2AP family was identified as a binding partner. A proline-rich motif of
      CFBP is recognized by one of the three Src-homology 3 domains of CIN85/CD2AP, and
      the affinity of the interaction is regulated by the tyrosine phosphorylation of
      CFBP. They co-localize in actinenriched structures, and overexpression of CFBP
      induced morphological changes with actin reorganization. Furthermore, CFBP
      accelerated the EGF receptor's down-regulation by facilitating the recruitment of
      Cbl to the CD2AP/CIN85 complex. Two spliced variants of CFBP lacking either exon
      5 or 8 are also expressed, and the variant lacking exon 5 without the proline
      rich motif lacks the ability to bind to the CIN85/CD2AP family. The CFBP protein
      seems to play a key role in the ligand-mediated internalization and down
      regulation of the EGF receptor.

PMID- 16895920
TI  - Molecular and functional interactions between Escherichia coli nucleoside
      diphosphate kinase and the uracil-DNA glycosylase Ung.
AB  - Escherichia coli nucleoside-diphosphate kinase (Ndk) catalyzes nucleoside
      triphosphate synthesis and maintains intracellular triphosphate pools. Mutants of
      E. coli lacking Ndk exhibit normal growth rates but show a mutator phenotype that
      cannot be entirely attributed to the absence of Ndk catalytic activity or to an
      imbalance in cellular triphosphates. It has been suggested previously that Ndk,
      similar to its human counterparts, possesses nuclease and DNA repair activities,
      including the excision of uracil from DNA, an activity normally associated with
      the Ung and Mug uracil-DNA glycosylases (UDGs) in E. coli. Here we have
      demonstrated that recombinant Ndk purified from wild-type E. coli contains
      significant UDG activity that is not intrinsic, but rather, is a consequence of a
      direct physical and functional interaction between Ung and Ndk, although a
      residual amount of intrinsic UDG activity exists as well. Co-purification of Ung
      and Ndk through multicolumn low pressure and nickel-nitrilotriacetic acid
      affinity chromatography suggests that the interaction occurs in a cellular
      context, as was also suggested by co-immunoprecipitation of endogenous Ung and
      Ndk from cellular extracts. Glutathione S-transferase pulldown and far Western
      analyses demonstrate that the interaction also occurs at the level of purified
      protein, suggesting that it is specific and direct. Moreover, significant
      augmentation of Ung catalytic activity by Ndk was observed, suggesting that the
      interaction between the two enzymes is functionally relevant. These findings
      represent the first example of Ung interacting with another E. coli protein and
      also lend support to the recently discovered role of nucleoside-diphosphate
      kinases as regulatory components of multiprotein complexes.

PMID- 16895922
TI  - The HicAB cassette, a putative novel, RNA-targeting toxin-antitoxin system in
      archaea and bacteria.
AB  - Toxin-antitoxin systems (TAS) are abundant, diverse, horizontally mobile gene
      modules that encode powerful resistance mechanisms in prokaryotes. We use the
      comparative-genomic approach to predict a new TAS that consists of a two-gene
      cassette encoding uncharacterized HicA and HicB proteins. Numerous bacterial and
      archaeal genomes encode from one to eight HicAB modules which appear to be highly
      prone to horizontal gene transfer. The HicB protein (COG1598/COG4226) has a
      partially degraded RNAse H fold, whereas HicA (COG1724) contains a double
      stranded RNA-binding domain. The stable combination of these two domains suggests
      a link to RNA metabolism, possibly, via an RNA interference-type mechanism. In
      most HicB proteins, the RNAse H-like domain is fused to a DNA-binding domain,
      either of the ribbon-helix-helix or of the helix-turn-helix class; in other TAS,
      proteins containing these DNA-binding domains function as antitoxins. Thus, the
      HicAB module is predicted to be a novel TAS whose mechanism involves RNA-binding
      and, possibly, cleavage.

PMID- 16895921
TI  - RuvABC is required to resolve holliday junctions that accumulate following
      replication on damaged templates in Escherichia coli.
AB  - RuvABC is a complex that promotes branch migration and resolution of Holliday
      junctions. Although ruv mutants are hypersensitive to UV irradiation, the
      molecular event(s) that necessitate RuvABC processing in vivo are not known.
      Here, we used a combination of two-dimensional gel analysis and electron
      microscopy to reveal that although ruvAB and ruvC mutants are able to resume
      replication following arrest at UV-induced lesions, molecules that replicate in
      the presence of DNA damage accumulate unresolved Holliday junctions. The failure
      to resolve the Holliday junctions on the fully replicated molecules correlates
      with a delayed loss of genomic integrity that is likely to account for the loss
      of viability in these cells. The strand exchange intermediates that accumulate in
      ruv mutants are distinct from those observed at arrested replication forks and
      are not subject to resolution by RecG. These results indicate that the Holliday
      junctions observed in ruv mutants are intermediates of a repair pathway that is
      distinct from that of the recovery of arrested replication forks. A model is
      proposed in which RuvABC is required to resolve junctions that arise during the
      repair of a subset of nonarresting lesions after replication has passed through
      the template.

PMID- 16895923
TI  - Few crucial links assure checkpoint efficiency in the yeast cell-cycle network.
AB  - MOTIVATION: The ability of cells to complete mitosis with high fidelity relies on
      elaborate checkpoint mechanisms. We study S- and M-phase checkpoint responses in
      silico in the budding yeast with a stochastic dynamical model for the cell-cycle.
      We aim to provide an unbiased functional classification of network interactions
      that reflect the contribution of each link to checkpoint efficiency in the
      presence of cellular fluctuations. RESULTS: We developed an algorithm BNetDyn to
      compute stochastic dynamical trajectories for an input gene network and its
      structural perturbations. User specified output measures like the mutual
      information between trigger and output nodes are then evaluated on the stationary
      state of the Markov process. Systematic perturbations of the yeast cell-cycle
      model by Li et al. classify each link according to its effect on checkpoint
      efficiencies and stabilities of the main cell-cycle phases. This points to the
      crosstalk in the cascades downstream of the SBF/MBF transcription activator
      complexes as determinant for checkpoint optimality; a finding that consistently
      reflects recent experiments. Finally our stochastic analysis emphasizes how
      dynamical stability in the yeast cell-cycle network crucially relies on backward
      inhibitory circuits next to forward induction. AVAILABILITY: C++ source code and
      network models can be downloaded at http://www.vital-it.ch/Software/

PMID- 16895924
TI  - MLR-tagging: informative SNP selection for unphased genotypes based on multiple
      linear regression.
AB  - The search for the association between complex diseases and single nucleotide
      polymorphisms (SNPs) or haplotypes has recently received great attention. For
      these studies, it is essential to use a small subset of informative SNPs
      accurately representing the rest of the SNPs. Informative SNP selection can
      achieve (1) considerable budget savings by genotyping only a limited number of
      SNPs and computationally inferring all other SNPs or (2) necessary reduction of
      the huge SNP sets (obtained, e.g. from Affymetrix) for further fine haplotype
      analysis. A novel informative SNP selection method for unphased genotype data
      based on multiple linear regression (MLR) is implemented in the software package
      MLR-tagging. This software can be used for informative SNP (tag) selection and
      genotype prediction. The stepwise tag selection algorithm (STSA) selects
      positions of the given number of informative SNPs based on a genotype sample
      population. The MLR SNP prediction algorithm predicts a complete genotype based
      on the values of its informative SNPs, their positions among all SNPs, and a
      sample of complete genotypes. An extensive experimental study on various datasets
      including 10 regions from HapMap shows that the MLR prediction combined with
      stepwise tag selection uses fewer tags than the state-of-the-art method of
      Halperin et al. (2005). AVAILABILITY: MLR-Tagging software package is publicly
      available at http://alla.cs.gsu.edu/~software/tagging/tagging.html

PMID- 16895925
TI  - Robust inference of positive selection from recombining coding sequences.
AB  - MOTIVATION: Accurate detection of positive Darwinian selection can provide
      important insights to researchers investigating the evolution of pathogens.
      However, many pathogens (particularly viruses) undergo frequent recombination and
      the phylogenetic methods commonly applied to detect positive selection have been
      shown to give misleading results when applied to recombining sequences. We
      propose a method that makes maximum likelihood inference of positive selection
      robust to the presence of recombination. This is achieved by allowing tree
      topologies and branch lengths to change across detected recombination
      breakpoints. Further improvements are obtained by allowing synonymous
      substitution rates to vary across sites. RESULTS: Using simulation we show that,
      even for extreme cases where recombination causes standard methods to reach false
      positive rates >90%, the proposed method decreases the false positive rate to
      acceptable levels while retaining high power. We applied the method to two HIV-1
      datasets for which we have previously found that inference of positive selection
      is invalid owing to high rates of recombination. In one of these (env gene) we
      still detected positive selection using the proposed method, while in the other
      (gag gene) we found no significant evidence of positive selection. AVAILABILITY:
      A HyPhy batch language implementation of the proposed methods and the HIV-1
      datasets analysed are available at
      http://www.cbio.uct.ac.za/pub_support/bioinf06. The HyPhy package is available at
      http://www.hyphy.org, and it is planned that the proposed methods will be
      included in the next distribution. RDP2 is available at
      http://darwin.uvigo.es/rdp/rdp.html

PMID- 16895926
TI  - Branch and bound computation of exact p-values.
AB  - P-value computation is often used in bioinformatics to quantify the surprise, or
      significance, associated with a given observation. An implementation is provided
      that computes the exact p-value associated with any observed sample, against a
      null multinomial distribution, using the likelihood-ratio statistic. The
      efficient branch and bound code, far exceeding the full enumeration implemented
      by commercial packages, is especially useful with small sample, sparse data and
      rare events, common scenarios in bioinformatics, where approximations are often
      inaccurate and inappropriate. This code base can also be adapted to compute exact
      p-values of other statistics in diverse sampling scenarios. AVAILABILITY: Freely
      available at http://www.soe.ucsc.edu/~jill/src/.

PMID- 16895927
TI  - HiRes--a tool for comprehensive assessment and interpretation of metabolomic
      data.
AB  - The increasing role of metabolomics in system biology is driving the development
      of tools for comprehensive analysis of high-resolution NMR spectral datasets.
      This task is quite challenging since unlike the datasets resulting from other
      'omics', a substantial preprocessing of the data is needed to allow successful
      identification of spectral patterns associated with relevant biological
      variability. HiRes is a unique stand-alone software tool that combines standard
      NMR spectral processing functionalities with techniques for multi-spectral
      dataset analysis, such as principal component analysis and non-negative matrix
      factorization. In addition, HiRes contains extensive abilities for data
      cleansing, such as baseline correction, solvent peak suppression, removal of
      frequency shifts owing to experimental conditions as well as auxiliary
      information management. Integration of these components together with
      multivariate analytical procedures makes HiRes very capable of addressing the
      challenges for assessment and interpretation of large metabolomic datasets,
      greatly simplifying this otherwise lengthy and difficult process and assuring
      optimal information retrieval. AVAILABILITY: HiRes is freely available for
      research purposes at http://hatch.cpmc.columbia.edu/highresmrs.html

PMID- 16895928
TI  - Group testing for pathway analysis improves comparability of different microarray
      datasets.
AB  - MOTIVATION: The wide use of DNA microarrays for the investigation of the cell
      transcriptome triggered the invention of numerous methods for the processing of
      microarray data and lead to a growing number of microarray studies that examine
      the same biological conditions. However, comparisons made on the level of gene
      lists obtained by different statistical methods or from different datasets hardly
      converge. We aimed at examining such discrepancies on the level of apparently
      affected biologically related groups of genes, e.g. metabolic or signalling
      pathways. This can be achieved by group testing procedures, e.g. over
      representation analysis, functional class scoring (FCS), or global tests.
      RESULTS: Three public prostate cancer datasets obtained with the same microarray
      platform (HGU95A/HGU95Av2) were analyzed. Each dataset was subjected to
      normalization by either variance stabilizing normalization (vsn) or mixed model
      normalization (MMN). Then, statistical analysis of microarrays was applied to the
      vsn-normalized data and mixed model analysis to the data normalized by MMN. For
      multiple testing adjustment the false discovery rate was calculated and the
      threshold was set to 0.05. Gene lists from the same method applied to different
      datasets showed overlaps between 42 and 52%, while lists from different methods
      applied to the same dataset had between 63 and 85% of genes in common. A number
      of six gene lists obtained by the two statistical methods applied to the three
      datasets was then subjected to group testing by Fisher's exact test. Group
      testing by GSEA and global test was applied to the three datasets, as well.
      Fisher's exact test followed by global test showed more consistent results with
      respect to the concordance between analyses on gene lists obtained by different
      methods and different datasets than the GSEA. However, all group testing methods
      identified pathways that had already been described to be involved in the
      pathogenesis of prostate cancer. Moreover, pathways recurrently identified in
      these analyses are more likely to be reliable than those from a single analysis
      on a single dataset.

PMID- 16895929
TI  - UniGene Tabulator: a full parser for the UniGene format.
AB  - UniGene Tabulator 1.0 provides a solution for full parsing of UniGene flat file
      format; it implements a structured graphical representation of each data field
      present in UniGene following import into a common database managing system usable
      in a personal computer. This database includes related tables for sequence,
      protein similarity, sequence-tagged site (STS) and transcript map interval
      (TXMAP) data, plus a summary table where each record represents a UniGene
      cluster. UniGene Tabulator enables full local management of UniGene data,
      allowing parsing, querying, indexing, retrieving, exporting and analysis of
      UniGene data in a relational database form, usable on Macintosh (OS X 10.3.9 or
      later) and Windows (2000, with service pack 4, XP, with service pack 2 or later)
      operating systems-based computers. AVAILABILITY: The current release, including
      both the FileMaker runtime applications, is freely available at
      http://apollo11.isto.unibo.it/software/

PMID- 16895930
TI  - Predicting the insurgence of human genetic diseases associated to single point
      protein mutations with support vector machines and evolutionary information.
AB  - MOTIVATION: Human single nucleotide polymorphisms (SNPs) are the most frequent
      type of genetic variation in human population. One of the most important goals of
      SNP projects is to understand which human genotype variations are related to
      Mendelian and complex diseases. Great interest is focused on non-synonymous
      coding SNPs (nsSNPs) that are responsible of protein single point mutation.
      nsSNPs can be neutral or disease associated. It is known that the mutation of
      only one residue in a protein sequence can be related to a number of pathological
      conditions of dramatic social impact such as Alzheimer's, Parkinson's and
      Creutzfeldt-Jakob's diseases. The quality and completeness of presently available
      SNPs databases allows the application of machine learning techniques to predict
      the insurgence of human diseases due to single point protein mutation starting
      from the protein sequence. RESULTS: In this paper, we develop a method based on
      support vector machines (SVMs) that starting from the protein sequence
      information can predict whether a new phenotype derived from a nsSNP can be
      related to a genetic disease in humans. Using a dataset of 21 185 single point
      mutations, 61% of which are disease-related, out of 3587 proteins, we show that
      our predictor can reach more than 74% accuracy in the specific task of predicting
      whether a single point mutation can be disease related or not. Our method,
      although based on less information, outperforms other web-available predictors
      implementing different approaches. AVAILABILITY: A beta version of the web tool
      is available at http://gpcr.biocomp.unibo.it/cgi/predictors/PhD-SNP/PhD-SNP.cgi

PMID- 16895932
TI  - COPA--cancer outlier profile analysis.
AB  - Chromosomal translocations are common in cancer, and in some cases may be causal
      in the progression of the disease. Using microarrays, in which the expression of
      thousands of genes are simultaneously measured, could potentially allow one to
      detect recurrent translocations for a particular cancer type. Standard
      statistical tests, such as the t-test are not suited for detecting these
      translocations, but a simple test based on robust centering and scaling of the
      data to help detect outlier samples, followed by a search for pairs of samples
      with mutually exclusive outliers, may be used to find genes involved in recurrent
      translocations. We have implemented this method, termed Cancer Outlier Profile
      Analysis (COPA) in an R package (that we call the copa package), and show its
      applicability on a publicly available dataset. AVAILABILITY:
      http://www.bioconductor.org

PMID- 16895931
TI  - A large quantity of novel human antisense transcripts detected by LongSAGE.
AB  - MOTIVATION: Taking advantage of the high sensitivity and specificity of LongSAGE
      tag for transcript detection and genome mapping, we analyzed the 632 813 unique
      human LongSAGE tags deposited in public databases to identify novel human
      antisense transcripts. RESULTS: Our study identified 45 321 tags that match the
      antisense strand of 9804 known mRNA sequences, 6606 of which contain antisense
      ESTs and 3198 are mapped only by SAGE tags. Quantitative analysis showed that the
      detected antisense transcripts are present at levels lower than their counterpart
      sense transcripts. Experimental results confirmed the presence of antisense
      transcripts detected by the antisense tags. We also constructed an antisense tag
      database that can be used to identify the antisense SAGE tags originated from the
      antisense strand of known mRNA sequences included in the RefSeq database.
      CONCLUSIONS: Our study highlights the benefits of exploring SAGE data for
      comprehensive identification of human antisense transcripts and demonstrates the
      prevalence of antisense transcripts in the human genome.

PMID- 16895933
TI  - ARFA: a program for annotating bacterial release factor genes, including
      prediction of programmed ribosomal frameshifting.
AB  - Correct annotation of genes encoding release factors in bacterial genomes is
      often complicated by utilization of +1 programmed ribosomal frameshifting during
      synthesis of release factor 2, RF2. In the absence of robust computational
      approaches for predicting ribosomal frameshifting, the success of proper
      annotation depends on annotators' familiarity with this phenomenon. Here we
      describe a novel computer tool that allows automatic discrimination of genes
      encoding class-I bacterial release factors, RF1, RF2 and RFH. Most usefully, this
      program identifies and automatically annotates +1 frameshifting in RF2 encoding
      genes. Comparison of ARFA performance with existing annotations of bacterial
      genomes revealed that only 20% of RF2 genes utilizing ribosomal frameshifting
      during their expression are annotated correctly. AVAILABILITY: The PHP based web
      interface of ARFA and the source code are located at
      http://recode.genetics.utah.edu/arfa

PMID- 16895934
TI  - The acquisition of full fluoroquinolone resistance in Salmonella Typhi by
      accumulation of point mutations in the topoisomerase targets.
AB  - OBJECTIVES: To determine the contribution to fluoroquinolone resistance of point
      mutations in the gyrA and parC genes of Salmonella Typhi. METHODS: Point
      mutations that result in Ser-83-->Phe, Ser-83-->Tyr and Asp-87-->Asn amino acid
      substitutions in GyrA and Glu-84-->Lys in ParC were introduced into a quinolone
      susceptible, attenuated strain of Salmonella Typhi using suicide vector
      technology. This is the first time that this approach has been used in Salmonella
      and abrogates the need for selection with quinolone antibacterials in the
      investigation of resistance mutations. RESULTS: A panel of mutants was created
      using this methodology and tested for quinolone resistance. The ParC substitution
      alone made no difference to quinolone susceptibility. Any single GyrA
      substitution resulted in resistance to nalidixic acid (MIC >or= 512 mg/L) and
      increased by up to 23-fold the MIC of the fluoroquinolones ofloxacin (MIC <or= 2
      mg/L) ciprofloxacin (MIC <or= 1 mg/L) and gatifloxacin (MIC <or= 0.38 mg/L).
      Among the double substitution mutants, those with a substitution in ParC were
      less prone to killing with ciprofloxacin. The triple substitution mutants (Ser-83
      ->Phe or Tyr and Asp-87-->Asn in GyrA with Glu-84-->Lys in ParC) showed high
      levels of resistance to all the fluoroquinolones tested (MICs: gatifloxacin, 3-4
      mg/L; ofloxacin, 32 mg/L; ciprofloxacin, 32-64 mg/L). CONCLUSIONS: In Salmonella
      Typhi the fluoroquinolones tested act on GyrA and, at higher concentrations, on
      ParC. The point mutations conferred reduced susceptibility to ofloxacin and
      ciprofloxacin, and also reduced susceptibility to gatifloxacin. Three mutations
      conferred resistance to ofloxacin (32 mg/L), ciprofloxacin (32 mg/L) and to the
      more active fluoroquinolone gatifloxacin (MIC >or= 3 mg/L). These results predict
      that the use of ofloxacin or ciprofloxacin will select for resistance to
      gatifloxacin in nature.

PMID- 16895935
TI  - Selective intracellular accumulation of the major metabolite issued from the
      activation of the prodrug ethionamide in mycobacteria.
AB  - BACKGROUND: Ethionamide is one of the most widely used drugs for the treatment of
      multidrug-resistant tuberculosis (MDR-TB). Like isoniazid, and pyrazinamide,
      ethionamide is a prodrug that needs to be activated by a mycobacterial enzyme.
      Activation pathways of prodrugs are generally problematic to uncover as they
      produce intermediates potentially difficult to characterize, to purify and that
      might prove unstable outside of their cellular context. OBJECTIVES AND METHODS:
      We have used high resolution magic angle spinning-NMR (HRMAS-NMR) to follow
      ethionamide activation directly within living mycobacterial cells. RESULTS: Data
      indicated that the intracellular metabolization of ethionamide strictly depends
      on the presence of the monooxygenase EthA and that EthA-dependent activation of
      ethionamide is coupled to a precise molecular sorting mechanism of the
      ethionamide metabolites. We found that the previously identified ethionamide
      metabolite 2-ethyl-4-hydroxymethylpyridine is produced in substantial amounts by
      the ethionamide-treated mycobacteria and that it is present exclusively outside
      of the bacteria. In contrast, the still unidentified ethionamide metabolite ETH*
      is the only ethionamide derivative detected within the bacterial cell. Moreover,
      ETH* appears to be unable to cross the bacterial envelope and consequently
      accumulates within the cytoplasm of the ethionamide-treated mycobacteria.
      CONCLUSIONS: These results strongly suggest that ETH* is the active
      antimycobacterial ethionamide derivative and open new perspectives for the
      understanding of the mode of action of prodrugs.

PMID- 16895936
TI  - Risk factors for nosocomial infections due to Pseudomonas aeruginosa producing
      metallo-beta-lactamase in two tertiary-care teaching hospitals.
AB  - OBJECTIVES: To assess risk factors for nosocomial infections due to Pseudomonas
      aeruginosa producing metallo-beta-lactamase (MBL-PA) in two teaching hospitals
      where horizontal dissemination has been demonstrated. METHODS: A case-control
      study was performed in both hospitals (assigned as hospital 1 and 2). Cases were
      patients with MBL-PA infections and controls were those with non-MBL-PA
      infections. Multivariate analysis was performed to identify independent risk
      factors. RESULTS: A total of 86 cases and 212 controls were included in the
      study. A logistic regression model showed that exposure to beta-lactams [odds
      ratio (OR) 3.21; 95% confidence interval (CI) 1.74-5.93] or fluoroquinolones (OR
      3.50; 95% CI 1.46-8.37) was associated with MBL-PA infections. Other independent
      risk factors were neurological disease (OR 3.00; 95% CI 1.61-5.58), urinary tract
      infection (OR 2.48; 95% CI 1.21-5.09) and renal failure (OR 2.29; 95% CI 1.13
      4.65). Admission to hospital 1 (OR 5.97; 95% CI 3.45-14.09) and intensive care
      unit stay (OR 2.07; 95% CI 1.46-3.96) were also associated with increased risk
      for MBL-PA infections. CONCLUSIONS: beta-Lactam exposure is an important risk
      factor for MBL-PA infections even in a setting where patient-to-patient
      transmission plays a major role in the spread of the isolates. Other risk factors
      deserve further investigation, particularly exposure to fluoroquinolones.

PMID- 16895937
TI  - 2-Hydroxypropyl-beta-cyclodextrin improves the effectiveness of albendazole
      against encapsulated larvae of Trichinella spiralis in a murine model.
AB  - OBJECTIVES: We evaluated whether the effectiveness of albendazole against
      encapsulated larvae increases when 2-hydroxypropyl-beta-cyclodextrin (HP-betaCD)
      is added to improve bioavailability. METHODS: Mice were infected with Trichinella
      spiralis and treated with albendazole alone, albendazole plus HP-betaCD or not at
      all (controls) (Experiment I). Both immediately after treatment [76 days post
      infection (p.i.)] and later (139 days p.i.) larvae were recovered, and the mean
      count was expressed in proportion to the larva count for controls. To evaluate
      the infectivity of the recovered larvae, the larvae recovered at 76 days p.i. and
      139 days p.i. were used to infect another three groups (Experiments II and III,
      respectively). RESULTS: At 76 days p.i., the percentage of larvae recovered was
      77.4% for mice treated with albendazole alone and 61.2% for those treated with
      albendazole plus HP-betaCD; at 139 days p.i., these percentages were 67.4% and
      40.9%, respectively (Experiment I). In Experiments II and III, the percentage of
      larvae collected from the albendazole group and the combined-treatment group was
      55.2% and 27.6%, and 53.1% and 26.6%, respectively. The ABZSO active metabolite
      was analysed to determine the bioavailability of albendazole. For the combined
      treatment group, the area under the plasma concentration-time curve between 0 and
      6 h was higher than that for the albendazole group. CONCLUSIONS: These data
      suggest that HP-betaCD increases the bioavailability and consequently the
      effectiveness of albendazole against encapsulated Trichinella larvae.

PMID- 16895938
TI  - Subinhibitory quinupristin/dalfopristin attenuates virulence of Staphylococcus
      aureus.
AB  - OBJECTIVES: The semi-synthetic streptogramin quinupristin/dalfopristin antibiotic
      exerts potent bactericidal activity against Staphylococcus aureus. We
      investigated whether, like other bactericidal antibiotics used at subinhibitory
      concentrations, quinupristin/dalfopristin enhances release of toxins by Gram
      positive cocci. METHODS: The activity of quinupristin/dalfopristin on exotoxin
      release by S. aureus was investigated by 2D SDS-PAGE combined with MALDI-TOF/MS
      analysis and by western blotting. RESULTS: We show that quinupristin/dalfopristin
      at subinhibitory concentrations reduces the release of S. aureus factors that
      induce tumour necrosis factor secretion in macrophages. Furthermore,
      quinupristin/dalfopristin but not linezolid attenuated S. aureus-mediated killing
      of infected host cells. When added to S. aureus cultures at different stages of
      bacterial growth, quinupristin/dalfopristin reduced in a dose-dependent manner
      the release of specific virulence factors (e.g. autolysin, protein A, alpha- and
      beta-haemolysins, lipases). In contrast, other presumably non-toxic exoproteins
      remained unchanged. CONCLUSIONS: The results of the present study suggest that
      subinhibitory quinupristin/dalfopristin inhibits virulence factor release by S.
      aureus, which might be especially helpful for the treatment of S. aureus
      infections, where both bactericidal as well as anti-toxin activity may be
      advantageous.

PMID- 16895939
TI  - Monitoring the toxicity of antiretroviral therapy in resource limited settings: a
      prospective clinical trial cohort in Thailand.
AB  - BACKGROUND: One of the many challenges which come together with the
      implementation of antiretroviral therapy (ART) in settings with limited resources
      is the monitoring of toxicity. This monitoring increases costs of ART and strains
      resources. We therefore investigated the necessity for laboratory toxicity
      monitoring of ART in Thailand. DESIGN, METHODS AND PARTICIPANTS: A prospective
      Thai cohort of 417 HIV-infected patients were enrolled in randomized clinical
      trials investigating ART. Time-dependent occurrence of grade III/IV abnormal
      laboratory values as defined by the AIDS Clinical Trial Group was analysed.
      RESULTS: During a median observation period of 3.7 years (2.4-4.3) 142 grade
      III/IV toxicities occurred in 101 (24.2%) patients. Hepatic toxicity (n = 33,
      7.9%), hypercholesterolaemia (n = 57, 13.7%), hypertriglyceridaemia (n = 26,
      6.2%), anaemia (n = 16, 3.8%) and low platelet counts (n = 8, 1.9%) were
      frequently observed. Anaemia and low platelets occurred early and during the
      first 2 years of ART. Hepatic toxicity was seen early and throughout the
      observation period. Hypertriglyceridaemia and hypercholesterolaemia occurred
      throughout the observation period, and increased over time. Hypercreatininaemia
      and hyperglycaemia occurred once after 120 and 132 weeks. ART was changed or
      interrupted for grade III/IV hepatic toxicity, anaemia and hyperglycaemia only.
      The incidence rate for grade III/IV toxicity was between 5.56 (95% CI, 6.76
      18.02) for low platelet counts and 41.18 (31.77-53.39) per 1000 patient years for
      hypercholesterolaemia. Antiretrovirals used were zidovudine, stavudine,
      lamivudine, zalcitabine, didanosine, efavirenz, saquinavir, ritonavir and
      indinavir. CONCLUSIONS: Grade III/IV toxicity is frequently observed in Thai
      patients treated with ART. The simple and inexpensive monitoring of ALT and
      haemoglobin could prevent most serious short-term toxicity. Long-term toxicity
      can be addressed with a yearly monitoring of triglycerides, cholesterol, glucose
      and creatinine if nephrotoxic drugs are used.

PMID- 16895940
TI  - Pharmacokinetics and peritoneal penetration of moxifloxacin in peritonitis.
AB  - OBJECTIVES: To investigate the penetration of moxifloxacin into peritoneal
      exudate in patients with complicated intra-abdominal infections (cIAIs). PATIENTS
      AND METHODS: Patients (n = 10) with evidence of peritonitis who required surgery
      with drainage of the abdominal cavity received a single intravenous infusion of
      moxifloxacin, 400 mg, over 1 h. Plasma and peritoneal exudate samples were
      obtained over 24 h, and moxifloxacin concentrations were measured by HPLC with
      fluorescence detection. RESULTS: Plasma moxifloxacin concentrations decreased
      from a geometric mean of 3.61 mg/L at 1 h to 0.36 mg/L at 24 h. Concentrations in
      peritoneal exudate were highest 2 h after the start of the infusion, reaching a
      geometric mean of 3.32 mg/L, and declined to a geometric mean of 0.69 mg/L at 24
      h. The exudate/plasma concentration ratio rose from 1.45 at 2 h to 1.91 at 24 h;
      the 95% confidence intervals for the ratio excluded unity at all time points,
      suggesting that moxifloxacin penetrates and accumulates in peritoneal exudate.
      The area under the concentration-time curve (AUC) tended to be greater in
      exudate; the time to peak concentrations (T(max)) was longer in exudate than in
      plasma, as were half-life and mean residence time (MRT). CONCLUSIONS: Following
      intravenous administration, moxifloxacin penetrated peritoneal exudate in
      patients with peritonitis, achieving and maintaining concentrations that exceed
      the MICs for pathogens commonly isolated in cIAIs. These findings support the
      clinical use of moxifloxacin as treatment for cIAIs.

PMID- 16895941
TI  - Rifampicin/imipenem combination in the treatment of carbapenem-resistant
      Acinetobacter baumannii infections.
AB  - BACKGROUND: In the setting of a large endemic of Acinetobacter baumannii
      infections, treatment of those due to carbapenem-resistant strains, susceptible
      only to colistin, has become a major problem in our hospital during the past
      years. Successful results have been reported using colistin, but clinical
      experience with this antibiotic is limited. In our experimental studies using
      these strains in a mouse pneumonia model, the best results were observed with a
      combination of rifampicin and imipenem. METHODS: From July 2000 to September
      2001, we performed a pilot study with patients suffering from serious infections
      due to carbapenem-resistant A. baumannii. Patients were treated with a
      rifampicin/imipenem combination and followed up prospectively. Cultures were
      repeated during and after treatment, and in vitro activity of rifampicin was
      monitored. Genotyping of these strains was performed by means of PFGE. RESULTS:
      Ten patients were selected: four with ventilator-associated pneumonia, and six
      with other infections (one catheter-related bacteraemia, five surgical
      infections). Three patients died, two of whom were considered therapeutic
      failures. In five of the seven patients who were cured, other procedures were
      also performed such as surgical drainage or catheter removal. In vitro
      development of high resistance to rifampicin was shown in seven (70%). PFGE
      demonstrated that initial isolates and high-resistant strains belonged to the
      same clones. CONCLUSIONS: The results of our study argue against the use of a
      rifampicin/imipenem combination for the treatment of carbapenem-resistant A.
      baumannii infections. However, combinations of rifampicin with other antibiotics
      merit further studies.

PMID- 16895942
TI  - Geographic variation in the appropriate use of cesarean delivery.
AB  - There is enormous geographic variation in the use of cesarean delivery: For
      births over 2,500 grams, adjusted cesarean rates vary fourfold between low- and
      high-use areas. Even for births under 2,500 grams, high-use counties have rates
      that are double those of low-use ones. Higher cesarean rates are only partially
      explained by patient characteristics but are greatly influenced by nonmedical
      factors such as provider density, the capacity of the local health care system,
      and malpractice pressure. Areas with higher usage rates perform the intervention
      in medically less appropriate populations-that is, relatively healthier births
      and do not see improvements in maternal or neonatal mortality.

PMID- 16895944
TI  - Medical outcome after immediate computed tomography or admission for observation
      in patients with mild head injury: randomised controlled trial.
AB  - OBJECTIVE: To compare immediate computed tomography during triage for admission
      with observation in hospital in patients with mild head injury. DESIGN:
      Multicentre, pragmatic, non-inferiority randomised trial. SETTING: 39 acute
      hospitals in Sweden. PARTICIPANTS: 2602 patients (aged > or = 6) with mild head
      injury. INTERVENTIONS: Immediate computed tomography or admission for
      observation. MAIN OUTCOME MEASURE: Dichotomised extended Glasgow outcome scale (1
      7 v 8). The non-inferiority margin was 5 percentage points. RESULTS: At three
      months, 275 patients (21.4%) in the computed tomography group had not recovered
      completely compared with 300 (24.2%) admitted for observation. The difference was
      - 2.8 percentage points, non-significantly in favour of computed tomography (95%
      confidence interval - 6.1% to 0.6%). The worst outcomes (mortality and more
      severe loss of function) were similar between the groups. In the patients
      admitted for observation, there was a considerable delay in time to treatment in
      those who required surgery. None of the patients with normal findings on
      immediate computed tomography had complications later. Patients' satisfaction
      with the two strategies was similar. CONCLUSIONS: The use of computed tomography
      in the management of patients with mild head injury is feasible and leads to
      similar clinical outcomes compared with observation in hospital. TRIAL
      REGISTRATION: ISRCTN81464462.

PMID- 16895945
TI  - Immediate computed tomography or admission for observation after mild head
      injury: cost comparison in randomised controlled trial.
AB  - OBJECTIVE: To compare the costs of immediate computed tomography during triage
      for admission with those of observation in hospital in patients with mild head
      injury. DESIGN: Prospective cost effectiveness analysis within a multicentre,
      pragmatic randomised trial. SETTING: 39 acute hospitals in Sweden PARTICIPANTS:
      2602 patients (aged > or = 6) with mild head injury. INTERVENTIONS: Immediate
      computed tomography or admission for observation. MAIN OUTCOME MEASURES: Direct
      and indirect costs related to the mild head injury during the acute and three
      month follow-up period. RESULTS: Outcome after three months was similar for both
      strategies (non-significantly in favour of computed tomography). For the acute
      stage and complications, the cost was 461 euros (314 pounds sterling, 582
      dollars) per patient in the computed tomography group and 677 euros (462 pounds
      sterling, 854 dollars) in the observation group; an average of 32% less in the
      computed tomography group (216 euros, 95% confidence interval -272 to -164; P <
      0.001). Sensitivity analysis showed that computed tomography was the most cost
      effective strategy under a broad range of assumptions. After three months, total
      costs were 718 euros and 914 euros per patient-that is, 196 euros less in the
      computed tomography group (- 281 to - 114; P < 0.001). The lower cost of the
      computed tomography strategy at the acute stage thus remained unchanged during
      follow-up. CONCLUSION: Patients with mild head injury attending an emergency
      department can be managed more cost effectively with computed tomography rather
      than admission for observation in hospital. TRIAL REGISTRATION: ISRCTN81464462.

PMID- 16895946
TI  - Organ-targeted mutagenicity of nitrofurantoin in Big Blue transgenic mice.
AB  - Nitrofurans are widely used in human medicine, as nitrofurantoin and
      nifuroxazide, still prescribed for long-term antimicrobial prophylaxis of urinary
      tract and gastrointestinal infection in humans respectively. Recent experiments
      in mammals, as well as reports mentioning toxic effects in humans associated with
      a long-term use, specially in the case of nitrofurantoin, raised the need for
      reevaluating their genotoxicity. The objective of this study was to determine
      whether these two compounds induce a mutagenic effect in the Big Blue transgenic
      mouse mutation assay. Mice were orally treated either with nitrofurantoin or
      nifuroxazide for five consecutive days and sacrificed 3 weeks later. In order to
      optimize the genotoxic response, the doses used for each compound were 25-fold
      higher as the posology in humans. They corresponded to 50% of the highest doses
      tolerated by mice. The mutant frequency was determined from kidney, lung,
      bladder, caecum, colon, small intestine, spleen and stomach. A weak mutagenic
      response of nitrofurantoin-treated mice specifically in the kidney was observed.
      As in the case of other nitrofuran compounds, the mutation spectra determined
      from treated samples exhibited slightly more GC-->TA transversions as compared
      with untreated conditions. These data are relevant to the targeted action of
      nitrofurantoin as a urinary antimicrobial agent. No significant increase of
      mutants was detected in the case of nifuroxazide-treated mice whatever the organs
      analysed.

PMID- 16895947
TI  - Cis-unsaturated fatty acids stimulate reactive oxygen species generation and
      lipid peroxidation in human spermatozoa.
AB  - CONTEXT: Defective sperm function is the largest defined cause of human
      infertility; however, the etiology of this condition is poorly understood.
      Although oxidative stress is acknowledged as a key contributor to this pathology,
      there are also data indicating that defective human spermatozoa contain
      abnormally high amounts of cis-unsaturated fatty acids. This study investigated
      whether a causative relationship exists between these two attributes of impaired
      semen quality. OBJECTIVE: The objective of this study was to determine whether
      polyunsaturated fatty acids can induce oxidative stress in human spermatozoa.
      METHOD: Dihydroethidium and SYTOX Green were used in conjunction with flow
      cytometry and HPLC to investigate reactive oxygen species (ROS) generation by
      human spermatozoa after fatty acid exposure. RESULTS: Arachidonic acid (AA)
      induced a time- and dose-dependent increase in ROS generation by human
      spermatozoa that led to the promotion of peroxidative damage and a loss of sperm
      motility. This effect could not be blocked with inhibitors of the cyclooxygenase
      or lipoxygenase pathways of AA metabolism, rotenone, protein kinase C
      antagonists, or known inhibitors of plasma membrane redox systems. However, ROS
      generation could be triggered with other cis-unsaturated fatty acids including
      linoleic and docosahexaenoic acids. Saturated fatty acids, methyl esters of
      unsaturated fatty acids, or other amphiphiles were all ineffective. However in a
      cell-free system, AA could trigger a redox signal via mechanisms that were
      profoundly disrupted by diphenylene iodonium, a flavoprotein inhibitor.
      CONCLUSIONS: The presence of excess unsaturated fatty acids in defective human
      spermatozoa may precipitate the oxidative stress encountered in male infertility.

PMID- 16895948
TI  - Differential effects of a perioperative hyperinsulinemic normoglycemic clamp on
      the neurohumoral stress response during coronary artery surgery.
AB  - BACKGROUND: Hyperglycemia in patients undergoing coronary artery bypass grafting
      (CABG) is associated with adverse outcome. Although insulin infusion strategies
      are increasingly used to improve outcome, a pathophysiological rationale is
      currently lacking. The present study was designed to quantify the effects of a
      perioperative hyperinsulinemic normoglycemic clamp on the neurohumoral stress
      response during CABG. METHODS: Forty-four nondiabetic patients, scheduled for
      elective CABG, were randomized to either a control group (n = 22) receiving
      standard care or to a clamp group (n = 22) receiving additionally a perioperative
      hyperinsulinemic (regular insulin at a fixed rate of 0.1 IU.kg(-1).h(-1))
      normoglycemic (plasma glucose between 3.0 and 6.0 mmol.liter(-1)) clamp during 26
      h. We measured the endocrine response of the hypothalamus-pituitary-adrenal (HPA)
      axis, the sympathoadrenal axis, and glucagon, as well as plasma glucose and
      insulin at regular intervals from the induction of anesthesia at baseline through
      the end of the second postoperative day (POD). RESULTS: There were no differences
      in clinical outcome between the groups. In the control group, hyperglycemia
      developed at the end of surgery and remained present until the final measurement
      point on POD2, whereas plasma insulin levels remained unchanged until the morning
      of POD1. In the intervention group, normoglycemia was well maintained during the
      clamp, whereas insulin levels ranged between 600 and 800 pmol.liter(-1). In both
      groups, plasma ACTH and cortisol increased from 6 h after discontinuation of
      cardiopulmonary bypass onward. However, during the clamp period, a marked
      reduction in the HPA axis response was found in the intervention group, as
      reflected by a 47% smaller increase in area under the curve in plasma ACTH (P =
      0.035) and a 27% smaller increase in plasma cortisol (P = 0.002) compared with
      the control group. Compared with baseline, epinephrine and norepinephrine
      increased by the end of the clamp interval until POD2 in both groups.
      Surprisingly, the area under the curve of epinephrine levels was 47% higher (P =
      0.026) after the clamp interval in the intervention group as compared with the
      control group. CONCLUSION: A hyperinsulinemic normoglycemic clamp during CABG
      delays and attenuates the HPA axis response during the first 18 h of the
      myocardial reperfusion period, whereas after the clamp, plasma epinephrine is
      higher. The impact of delaying cortisol responses on clinical outcome of CABG
      remains to be elucidated.

PMID- 16895949
TI  - Radioactive iodine therapy for goitrous Hashimoto's thyroiditis.
AB  - CONTEXT: Hashimoto's thyroiditis is an autoimmune disease that can produce marked
      clinical symptoms when patients have large diffuse goiters. DESIGN: This
      retrospective cohort study was designed to evaluate whether radioactive iodine
      (RAI) is effective for Hashimoto's thyroiditis with a large goiter. Starting in
      November 1999, 13 Hashimoto's patients with large goiters, whose thyroiditis was
      refractory to TSH suppression therapy with thyroid hormone administration [two
      men and 11 women with a mean age of 61.2 +/- 8.9 yr (50-79 yr)], were recruited
      for the present study. The duration of symptomatic goiter before undergoing RAI
      was 12.0 +/- 7.9 yr (4-33 yr). Thirteen millicuries of 131I was administered two
      to six times, at an interval of 1-6 months on an outpatient basis. Thyroid weight
      was measured ultrasonographically, or by computed tomography if ultrasound was
      not possible due to the large size of the goiter. RESULTS: RAI was administered
      an average of 4.7 +/- 1.4 times (two to six times), with a total dose of 59.8 +/-
      17.3 mCi (25.0-78.0 mCi). The observation period was 47.9 +/- 13.4 months (26-66
      months) after the first RAI. The average weight of the thyroid gland was 125.3 +/
      57.7 g (42.9-269.4 g) before the first RAI, decreasing significantly to 49.7 +/-
      25.8 g (18.3-93.3 g) after the last RAI (P < 0.001, paired Student's t test). The
      percent reduction from baseline was 58.7 +/- 14.2% (35.7-84.0%). None of the
      patients showed an increase in goiter size or complained of a pressure sensation
      after any of the RAI treatments. CONCLUSION: RAI is effective in Hashimoto's
      thyroiditis with a large goiter.

PMID- 16895950
TI  - The relative roles of follicle-stimulating hormone and luteinizing hormone in
      maintaining spermatogonial maturation and spermiation in normal men.
AB  - CONTEXT: Male hormonal contraception via gonadotropin and intratesticular
      androgen withdrawal disrupts spermatogenesis at two principal sites: 1)
      spermatogonial maturation, and 2) spermiation. OBJECTIVE: The objective of this
      study was to explore the relative dependence of each stage of germ cell
      development on FSH and LH/intratesticular androgen action. DESIGN, SETTING, AND
      PARTICIPANTS: Eighteen men enrolled in this prospective, randomized 14-wk study
      at Prince Henry's Institute. INTERVENTIONS: Subjects (n = 6/group) were assigned
      to 6 wk of 1) testosterone (T) implant (4 x 200 mg sc once)+depot medroxy
      progesterone acetate (DMPA; 150 mg im once); 2) T implant+DMPA+FSH (300 IU sc
      twice weekly); and 3) T implant+DMPA+human chorionic gonadotropin (hCG; 1000 IU
      sc twice weekly as an LH substitute). Men then underwent a vasectomy and
      testicular biopsy with previously reported control data used for comparison. MAIN
      OUTCOME MEASURES: Germ cell number (assessed by the optical disector
      stereological approach) and intratesticular androgen levels were determined.
      RESULTS: T+DMPA alone significantly suppressed type B spermatogonia, preleptotene
      through to pachytene spermatocytes, and round spermatids from control (P < 0.05).
      All germ cell subtypes were maintained at control levels by either FSH or LH
      activity, except pachytene spermatocytes, which were found to be lower in the hCG
      vs. FSH (P < 0.01) and control groups (P < 0.05). CONCLUSIONS: FSH and LH
      maintained spermatogenesis independently in this gonadotropin-suppressed model.
      Compared with LH, FSH showed better maintenance of pachytene spermatocyte number,
      whereas improved conversion to round spermatids was suggested with hCG treatment.
      Future contraceptive treatment strategies must consider independent regulation of
      spermatogenesis by both FSH and LH/intratesticular androgens for maximum
      efficacy.

PMID- 16895952
TI  - Estradiol and regulation of anti-Mullerian hormone, inhibin-A, and inhibin-B
      secretion: analysis of small antral and preovulatory human follicles' fluid.
AB  - CONTEXT: In ovaries surgically removed for fertility preservation, hormone
      concentrations in fluid from small antral follicles were determined. Levels were
      compared with those found in preovulatory follicular fluid. OBJECTIVE: The
      objective of this study is to measure intrafollicular concentrations of anti
      Mullerian hormone (AMH), inhibin-A, inhibin-B, estradiol, and progesterone.
      SETTING: The study was set in a university hospital. PATIENTS: Patients were 22
      women suffering from a cancer disease and 16 women undergoing assisted
      reproduction. INTERVENTIONS: Fluid from 35 follicles (diameter, 3-8 mm) was
      included and compared with that of 32 preovulatory follicles. MAIN OUTCOME
      MEASURES: The main outcome measures were intrafollicular concentrations of the
      measured hormones and their possible correlation. RESULTS: Concentrations of AMH
      in small antral follicles were almost three orders of magnitude higher than in
      follicle fluid of preovulatory follicles, 790 +/- 95 vs. 1.17 +/- 0.14 ng/ml
      (mean +/- sem), respectively. There was a significant negative correlation
      between estradiol and AMH in fluid from small antral follicles, whereas inhibin-A
      and inhibin-B were correlated positively with estradiol concentrations.
      Progesterone showed a similar correlation to levels of AMH but only in fluid of
      preovulatory follicles. CONCLUSIONS: The high expression of AMH in granulosa
      cells of small antral follicles actually translates into very high follicle fluid
      AMH concentrations. This most likely explains the correlation between serum AMH
      levels and the number of small antral follicles as previously demonstrated. The
      negative correlation between estradiol and AMH suggests that FSH down-regulates
      AMH expression. Thus, the microenvironment of the follicle shows profound changes
      with developmental stage and highlights the importance of studies to understand
      the mechanisms that regulate follicular growth and development during antral
      stages of development.

PMID- 16895951
TI  - Midkine, a heparin-binding growth factor, selectively stimulates proliferation of
      definitive zone cells of the human fetal adrenal gland.
AB  - CONTEXT: In the human fetal adrenal gland (HFA), the inner fetal zone (FZ)
      secretes dehydroepiandrosterone sulfate. The function of the outer definitive
      zone (DZ) is less clear; however, the DZ phenotype is that of a reservoir of
      progenitor cells, many of which are mitotically active. Midkine (MK) is a heparin
      binding growth factor with various bioactivities. OBJECTIVE: The objective of
      this study was to investigate expression, proliferative effects, and ACTH
      regulation of MK in the HFA. DESIGN AND SETTING: RNA, cryosections, and primary
      cell cultures from HFAs (14-24 wk) and adult adrenal RNA were used. MAIN OUTCOME
      MEASURES: The main outcome measures were MK mRNA levels (measured by quantitative
      real-time RT-PCR); MK localization (measured by immunostaining); MK proliferative
      effects and mechanism (measured by proliferation assays, flow cytometry,
      pharmacological interventions); and ACTH regulation (measured by quantitative
      real-time RT-PCR). RESULTS: HFA MK mRNA levels were 4-fold higher than in adult
      adrenals (P < 0.05) and were comparable to levels in fetal and adult brains
      (positive controls). MK immunoreactivity was abundant throughout the HFA.
      Exogenous MK caused proliferation of isolated DZ cells but not FZ cells (72 h, P
      < 0.05). In contrast, basic fibroblast growth factor induced proliferation of
      cells from both zones. Pharmacological interventions indicated that MK-induced DZ
      cell proliferation may be mediated by phosphatidylinositol 3-kinase, MAPK kinase,
      and Src family kinases. ACTH (1 nm) increased MK mRNA by 3.5-fold (48 h, P <
      0.01) in isolated FZ cells. CONCLUSIONS: MK likely plays a key role in HFA
      development. MK's selective in vitro mitotic effects on DZ cells may provide
      insights into the mechanism underlying the distinct in vivo differences in
      mitotic activity between the DZ and FZ.

PMID- 16895953
TI  - Associations of body size at birth with late-life cortisol concentrations and
      glucose tolerance are modified by haplotypes of the glucocorticoid receptor gene.
AB  - CONTEXT: Small body size at birth is associated with cardiovascular disease and
      type 2 diabetes in adult life. This link may be in part mediated by early-life
      programming of the hypothalamic-pituitary-adrenal axis (HPAA) function.
      OBJECTIVE: Our objective was to assess whether haplotypes of the glucocorticoid
      receptor (GR) gene modify this link. DESIGN AND PARTICIPANTS: We conducted a
      birth cohort study that included 437 men and women born in Helsinki, Finland,
      during 1924-1933, whose birth measurements were recorded. MAIN OUTCOME MEASURES:
      We studied how the oral glucose tolerance test and fasting plasma total and free
      cortisol concentrations and, in a subset of 162 women, a more detailed HPAA
      evaluation, are predicted by body size at birth and haplotypes of the GR locus.
      We also measured the haplotype-specific relative mRNA expression level for the
      haplotype of interest. RESULTS: One of the haplotypes was associated with lower
      birth weight and length and higher fasting plasma and mean 24-h salivary
      cortisol. Moreover, this haplotype modified the association of length at birth
      with adult phenotypes; in carriers, short length at birth was associated with
      increased fasting plasma cortisol, cortisol/corticosteroid-binding globulin
      ratio, impaired glucose tolerance or diabetes [1 cm decrease corresponded to 1.36
      fold odds ratio; 95% confidence interval (CI), 1.09-1.70; P = 0.007], and higher
      120-min glucose (5.8%; 95% CI, 2.5-9.1%; P = 0.0007), but no association was seen
      in noncarriers (P for interaction was 0.06, 0.01, 0.02, and 0.01, respectively).
      The mRNA expression level of this haplotype was 93.7% (95% CI, 90.5-96.8%; P =
      2.2 x 10(-4)) of the expression level of the other haplotypes. CONCLUSIONS: A
      common GR haplotype may contribute to and modify the association of short length
      at birth with adult glucose tolerance and HPAA function by a mechanism that
      affects regulation of GR expression.

PMID- 16895954
TI  - Assessment of adrenal reserve in pregnancy: defining the normal response to the
      adrenocorticotropin stimulation test.
AB  - CONTEXT: Normal pregnancy is a state of hypercortisolism, making adrenal
      insufficiency difficult to diagnose. OBJECTIVE: We sought to identify a
      normative, minimum-response threshold for the ACTH stimulation test in pregnancy.
      We hypothesized that salivary free cortisol (SaFC) would prove a more
      physiological and less variable measure of adrenal reserve in pregnancy than
      serum cortisol (SC). DESIGN: This is a prospective study of normal controls.
      SETTING: The study was conducted in an obstetrical clinic in a tertiary care
      hospital. PATIENTS: Patients included 36 healthy ambulatory pregnant women (aged
      18-37 yr) with singleton pregnancies. INTERVENTION: The 250-microg ACTH
      stimulation test was performed in the healthy pregnant volunteers. Based on their
      gestational age at the time of recruitment, women were studied in one of the
      trimesters and were restudied at 11-14 wk postpartum. MAIN OUTCOME MEASURES:
      Total SC, aldosterone, and SaFC concentrations were measured before and after
      ACTH. The response in pregnancy was compared with postpartum values. RESULTS:
      Basal SC (P = 0.01), aldosterone (P = 0.001), and SaFC (P = 0.01) values
      progressively increased during the trimesters of pregnancy and decreased
      postpartum, confirming that pregnant women have increased basal glucocorticoid
      and mineralocorticoid production. There was enhanced responsiveness of the
      maternal adrenal glands to ACTH stimulation as pregnancy progressed, as measured
      by peak stimulated SaFC (P = 0.009) and aldosterone (P = 0.01). In the milieu of
      altered binding globulins, SaFC is a more consistent, binding-globulin
      independent measure of stimulated adrenal function than total SC. Minimum
      criteria for the normal SaFC response to ACTH stimulation in the second and third
      trimesters of pregnancy and postpartum have been generated based on a
      predominantly African-American group of subjects. CONCLUSIONS: Reliable data are
      available for the evaluation of the adrenal axis in pregnancy with a noninvasive,
      outpatient measure of SaFC. Glucocorticoid therapy in pregnancy should take into
      account that adrenal reserve increases as pregnancy progresses.

PMID- 16895956
TI  - Exercise training lowers plasma visfatin concentrations in patients with type 1
      diabetes.
AB  - CONTEXT: Exercise training exerts beneficial effects on metabolic and vascular
      risk factors in patients with type 1 diabetes mellitus (T1DM). It is unknown
      whether training also influences concentrations of visfatin, a novel insulin
      mimetic adipocytokine. OBJECTIVES: In this study, we have investigated whether
      plasma visfatin concentrations are altered by training in patients with T1DM.
      DESIGN AND PATIENTS: Fasting plasma visfatin concentrations and metabolic
      parameters were measured in 18 patients with T1DM who participated in a
      supervised aerobic exercise program for 4 months. Three subjects discontinued
      training prematurely after 2 months. Samples were obtained before and during
      training and 8 months after the end of regular exercise. Fourteen healthy young
      subjects served as controls. RESULTS: At baseline, patients with T1DM had higher
      visfatin concentrations than controls (64.1 +/- 12.0 vs. 1.3 +/- 0.0 ng/ml, P <
      0.01). Exercise reduced visfatin after 2 and 4 months to 27.8 +/- 2.6 (n = 18)
      and 17.5 +/- 3.4 ng/ml (n = 15), respectively (P < 0.001 for n = 15 subjects who
      participated in all visits, ANOVA). This effect was maintained 8 months after
      cessation of training, with visfatin concentrations of 19.7 +/- 5.0 ng/ml (n =
      15). Metabolic parameters were not affected by the training program. CONCLUSION:
      Elevated visfatin concentrations in patients with T1DM can be lowered by regular
      physical exercise. It is unknown whether glucose tolerance is affected by changes
      in visfatin concentrations.

PMID- 16895955
TI  - Increased subcutaneous and epicardial adipose tissue production of
      proinflammatory cytokines in cardiac surgery patients: possible role in
      postoperative insulin resistance.
AB  - CONTEXT: Hyperglycemia and insulin resistance frequently occur in critically ill
      patients even without a history of diabetes. OBJECTIVE: Our objective was to
      study the role of adipose tissue hormonal production in the development of
      insulin resistance in cardiac surgery patients. PARTICIPANTS, INTERVENTIONS, AND
      SETTINGS: Fifteen patients with elective cardiac surgery underwent blood sampling
      before, at the end, and 6, 12, 24, 48, and 120 h after the end of their
      operation. Epicardial and sc adipose tissue sampling was done at the beginning
      and at the end of surgery in the Department of Cardiac Surgery. MAIN OUTCOME
      MEASURES: We measured serum concentrations and sc and epicardial adipose tissue
      mRNA expression of IL-6, monocyte chemoattractant protein-1 (MCP-1), TNF-alpha,
      leptin, resistin, and adiponectin and sc and epicardial adipose tissue mRNA
      expression of CD14, CD45, and CD68. RESULTS: The rate of insulin infusion
      required to maintain euglycemia increased up to 7-fold 12 h after the operation,
      suggesting the development of insulin resistance. Serum IL-6 levels increased 43
      fold 12 h after surgery. MCP-1 peaked 6-fold at the end of surgery. Smaller peaks
      of TNF-alpha and leptin appeared 6 and 12 h after surgery, respectively. Resistin
      levels peaked 4-fold 24 h after surgery, but adiponectin levels were not
      significantly affected. TNF-alpha and CD45 mRNA expression increased markedly
      during the operation in sc adipose tissue. IL-6, resistin, and MCP-1 mRNA
      expression increased in both sc and epicardial adipose tissue. Leptin,
      adiponectin, CD14, and CD68 mRNA expression did not change significantly.
      CONCLUSIONS: Both sc and epicardial adipose tissue is a source of proinflammatory
      cytokines in cardiac surgery patients and may contribute to the development of
      postoperative insulin resistance.

PMID- 16895957
TI  - Efficacy of adjuvant radiotherapy of the tumor bed on local recurrence of
      adrenocortical carcinoma.
AB  - CONTEXT: Local tumor recurrence is common in adrenocortical carcinoma (ACC) and
      is the most frequent cause for reoperation. Although radiotherapy is often
      considered ineffective in the treatment of ACC, the limited number of available
      studies does not support this statement. OBJECTIVE: The objective of the study
      was investigation of adjuvant tumor bed irradiation in the treatment of ACC.
      DESIGN: We performed a retrospective analysis. PATIENTS: The German ACC Registry
      (n = 285) was screened for patients who had received tumor bed radiotherapy in an
      adjuvant setting (no macroscopic evidence for residual disease after surgery).
      Fourteen patients without distant metastases (World Health Organization stage I,
      one patient; stage II, seven; stage III, three; and stage IV, three) were matched
      with 14 patients for resection status, adjuvant mitotane treatment, stage, and
      tumor size. Median follow-up of patients still alive (n = 15) was 37 months. MAIN
      OUTCOME MEASURE: Survival without local recurrence and disease-free survival was
      the main outcome measure. RESULTS: Local recurrence was observed in two of 14
      patients in the radiotherapy group and in 11 of 14 control patients. The
      probability to be free of local recurrence 5 yr after surgery differed
      significantly [79% (95% confidence interval, 53-100) vs. 12% (0-30); P < 0.01].
      However, disease-free and overall survival were not significantly different
      between the two groups. Acute adverse events related to radiotherapy were mostly
      mild. One patient developed a partial Budd-Chiari syndrome. CONCLUSION: These
      data from the largest series of ACC patients treated with adjuvant tumor bed
      irradiation suggest that radiotherapy is effective in reducing the high rate of
      local recurrence in ACC. A randomized trial in high-risk patients is needed to
      further evaluate the efficacy of radiotherapy as an adjuvant treatment option in
      ACC.

PMID- 16895958
TI  - Prevalence of thyroid autoimmunity in sporadic idiopathic hypoparathyroidism in
      comparison to type 1 diabetes and premature ovarian failure.
AB  - CONTEXT: Thyroid autoimmunity is the most common coexistent endocrinopathy in
      type 1 diabetes (T1D), Addison's disease, and premature ovarian failure (POF).
      Although the role of autoimmunity is being investigated in patients with sporadic
      idiopathic hypoparathyroidism (SIH), there is little information on coexistent
      thyroid autoimmunity. OBJECTIVE: Our objective was to assess the prevalence of
      thyroid peroxidase autoantibodies (TPOAb) and thyroid dysfunction in patients
      with SIH and its comparison with that in T1D, POF, and Hashimoto's thyroiditis
      (HT) and age- and sex-matched healthy controls (for SIH). DESIGN AND SETTING: We
      conducted a case control study in a tertiary care setting. PATIENTS AND METHODS:
      Subjects were consecutive patients with SIH (n = 87), T1D (n = 100), POF (n =
      58), and HT (n = 47) and healthy controls (100 females and 64 males). Serum free
      T3, free T4, TSH, and TPOAb (normal < or = 34 IU/ml) were measured by
      electrochemiluminescence assay. Subjects with 1) serum TSH at least 5 microU/ml
      along with TPOAb more than 34 IU/ml; 2) TSH at least 10 microU/ml but normal
      TPOAb titers; or 3) Graves' disease were considered to have thyroid dysfunction.
      RESULTS: TPOAb positivity (> 34 IU/ml) in females was 14.6% in SIH, 24.1% in POF,
      and 42.1% in T1D compared with 76.6% in HT and 9% in healthy controls. The
      frequencies of TPOAb positivity and thyroid dysfunction in patients with SIH were
      comparable to those in control and POF groups, but significantly less than in T1D
      and HT groups. CONCLUSION: The frequencies of TPOAb and thyroid dysfunction were
      not significantly higher in patients with SIH than in healthy controls, unlike in
      patients with T1D and POF.

PMID- 16895960
TI  - Functional significance of polycystic-size ovaries in healthy adolescents.
AB  - CONTEXT: The relevance of adult polycystic ovary criteria to adolescence is
      unclear. OBJECTIVE: The objective was to determine the functional significance of
      polycystic-size ovaries (PSO) in healthy adolescents.
      DESIGN/SETTING/PARTICIPANTS/INTERVENTIONS: Healthy 11- to 18-yr-old
      postmenarcheal volunteers (n = 22) were recruited and divided into groups with
      normal size ovaries (VNSO; n = 10) or a polycystic-size ovary (VPSO; n = 12).
      They were secondarily compared with adolescents with polycystic ovary syndrome
      (PCOS; n = 8) matched for gynecological age and a PSO. All underwent GnRH agonist
      (GnRHag), oral glucose tolerance, and ACTH1-24 testing in our General Clinical
      Research Center. RESULTS: VPSO had a higher peak 17-hydroxyprogesterone (17PROG)
      response to GnRHag than VNSO (146 +/- 14 ng/dl, mean +/- sem, vs. 85 +/- 11; P =
      0.008), as well as larger ovaries (13.3 +/- 0.7 cc vs. 8.5 +/- 0.8 cc). VPSO peak
      17PROG was elevated (>137 ng/dl) in 42% (5 of 12). However, VPSO and VNSO
      androgen levels were similar, with the exception of one VPSO subject who had
      hyperandrogenemia and thus met criteria for PCOS. VPSO were similar to VNSO in
      LH, FSH, estradiol, and adrenal androgenic function. Although the VPSO group
      resembled the PCOS group in their 17PROG response to the GnRHag test, they
      differed in having significantly smaller ovaries and lower body mass index and in
      lacking evidence of peripheral androgen excess and of insulin resistance.
      CONCLUSION: A PSO in asymptomatic adolescents seems typically to be a normal
      variant. However, about half have a subclinical PCOS type of ovarian dysfunction;
      it is unknown whether this indicates a genetic carrier state or a risk for
      anovulation.

PMID- 16895959
TI  - Vascular endothelial and smooth muscle function relates to body mass index and
      glucose in obese and nonobese children.
AB  - CONTEXT: Endothelial and smooth muscle dysfunction are critical precursors of
      atherosclerosis. These can be detected in children at risk of cardiovascular
      disease. OBJECTIVE: The objective of this study is to evaluate endothelial and
      smooth muscle function and their determinants using flow-mediated dilatation
      (FMD) and glyceryl trinitrate-mediated dilatation (GTN) in obese, nonobese, and
      type 1 diabetes mellitus (T1DM) children. DESIGN: This is a cross-sectional
      study. SUBJECTS: The study subjects were 270 children [140 males, mean age 13.7
      (2.8) yr] including 58 obese, 53 nonobese, and 159 T1DM children. MEASUREMENTS:
      Vascular function (FMD and GTN), body mass index (BMI) z-score, blood pressure,
      glucose, glycosylated hemoglobin, lipids, folate, homocysteine, and high
      sensitive C-reactive protein were measured. RESULTS: FMD and GTN were
      significantly lower in obese and T1DM compared with nonobese subjects (P < 0.001,
      P < 0.001). FMD and GTN were similarly reduced in obese and T1DM subjects (P =
      0.22, P = 0.28). In all nondiabetic subjects (n = 111), both FMD and GTN were
      significantly and independently related to BMI z-score (r = -0.28, P = 0.003,
      beta = -0.36, P < 0.001) and weight z-score (beta = -0.31, P = 0.002; r = -0.52,
      P < 0.001). FMD related independently to total cholesterol (beta = -0.22, P =
      0.02). GTN related independently to vessel diameter (beta = -0.49, P < 0.001).
      GTN related to glucose within the normal range (r = -0.34, P = 0.001).
      CONCLUSIONS: Children with obesity and T1DM have a similar degree of vascular
      dysfunction. BMI and weight adjusted for age and sex relate to endothelial and
      smooth muscle function in nonobese and obese children. Glucose relates to smooth
      muscle function in nonobese nondiabetic children. This suggests a continuum
      effect of BMI and glucose within the normal range on vascular function in
      childhood.

PMID- 16895961
TI  - 99mTc-depreotide scintigraphy versus 18F-FDG-PET in the diagnosis of radioiodine
      negative thyroid cancer.
AB  - BACKGROUND: Papillary and follicular thyroid cancer were found recently to
      express somatostatin receptors (SSTRs). (99m)Tc-depreotide binds with high
      affinity to SSTRs 2, 3, and 5. AIM: The aim of this study was to evaluate the
      feasibility of applying (99m)Tc-depreotide scintigraphy to search for radioiodine
      negative thyroid cancer; comparison is made to a standard approach using (18)F
      fluorodeoxyglucose-positron emission tomography ((18)F-FDG-PET). PATIENTS AND
      METHODS: Ten radioiodine-negative patients with suspicion of recurrent or
      metastatic thyroid cancer were investigated with (99m)Tc-depreotide scintigraphy
      and (18)F-FDG-PET, performed with a time interval that ranged from 1-8 wk.
      Locoregional recurrence and metastases were confirmed by ultrasonography and/or
      computed tomography, together with cytology or histological examination in
      selected cases. RESULTS: True-positive results were obtained in nine patients
      (90%) with (99m)Tc-depreotide scintigraphy and in seven patients (70%) with (18)F
      FDG-PET. (99m)Tc-depreotide scintigraphy gave better results in terms of
      detection of recurrent or metastatic disease compared with (18)F-FDG-PET in three
      patients, whereas (18)F-FDG-PET identified metastatic disease that was not seen
      with (99m)Tc-depreotide in only one patient. (99m)Tc-depreotide scintigraphy
      portrayed lesions in three patients with negative morphological imaging.
      CONCLUSIONS: Results indicate a potential value of (99m)Tc-depreotide
      scintigraphy for the diagnosis of thyroid cancer in the setting of detectable
      thyroglobulin and negative radioiodine scan. Furthermore, (99m)Tc-depreotide adds
      complementary information regarding the SSTR status of lesions, which may be
      helpful for individual therapy planning in this group of patients, which is hard
      to manage clinically.

PMID- 16895963
TI  - The impact of glucocorticoid replacement regimens on metabolic outcome and
      comorbidity in hypopituitary patients.
AB  - BACKGROUND: Hypopituitary patients with untreated GH deficiency and patients on
      inappropriately high doses of glucocorticoid (GC) share certain clinical
      features. OBJECTIVE: The aim of the study was to examine the influence of GC
      substitution on clinical characteristics in hypopituitary patients before and
      after GH replacement therapy. METHOD: A total of 2424 hypopituitary patients
      within the KIMS (Pfizer International Metabolic Database) were grouped according
      to ACTH status. Comparisons were performed between subjects on hydrocortisone
      (HC) (n = 1186), cortisone acetate (CA) (n = 487), and prednisolone/dexamethasone
      (n = 52), and ACTH-sufficient patients (AS) (n = 717) before and after 1 yr of GH
      treatment in terms of body mass index, waist and hip circumference, blood
      pressure, glucose, glycosylated hemoglobin (HbA1c), serum lipids, IGF-I, and
      comorbidity. Hydrocortisone equivalent (HCeq) doses were calculated, and
      measurements were adjusted for sex and age. RESULTS: At baseline, the HC group
      had increased total cholesterol, triglycerides, waist circumference, and HbA1c,
      and the prednisolone/dexamethasone group had increased waist/hip ratio as
      compared with AS. After HCeq dose adjustment, the HC group retained higher HbA1c
      than the CA group. GC-treated patients showed a dose-related increase in serum
      IGF-I, body mass index, triglycerides, low-density lipoprotein cholesterol and
      total cholesterol levels. Subjects with HCeq doses less than 20 mg/d (n = 328) at
      baseline did not differ from AS in metabolic endpoints. The 1-yr metabolic
      response to GH was similar in all GC groups and dose categories. All new cases of
      diabetes (n = 12), stroke (n = 8), and myocardial infarction (n = 3) during GH
      treatment occurred in GC-treated subjects. CONCLUSION: HCeq doses of at least 20
      mg/d in adults with hypopituitarism are associated with an unfavorable metabolic
      profile. CA replacement may have metabolic advantages compared with other GCs.

PMID- 16895962
TI  - Androgen therapy induces muscle protein anabolism in older women.
AB  - CONTEXT: Normal healthy men and women undergo a gradual loss of skeletal muscle
      mass and strength with advancing age. While androgens are protein anabolic in
      older men, the metabolic effects in older women are poorly understood. OBJECTIVE
      AND DESIGN: The objective of this study was to determine whether oral
      administration of a synthetic derivative of testosterone [oxandrolone, Oxandrin
      (OX)] (7.5 mg orally twice daily for 14 d) to five older women (age, 65 +/- 2 yr)
      would enhance skeletal muscle anabolic biomarkers including mixed muscle
      fractional synthetic rate (FSR), net phenylalanine balance, androgen receptor,
      and IGF-I protein expression at d 0, 5, and 14 of treatment. As a positive
      control, seven older men were examined after 14 d of OX (10 mg orally twice
      daily). SETTING: The study was performed at the General Clinical Research Center.
      RESULTS: Fourteen days of OX significantly increased skeletal muscle FSR in older
      women (d 0, 0.073 +/- 0.006 vs. d 5, 0.092 +/- 0.006 vs. d 14, 0.115 +/-
      0.007%/h) (P < 0.05, d 0 vs. d 14). Conversely, OX stimulated FSR in older men
      after only 5 d (d 0, 0.061 +/- 0.003 vs. d 5, 0.101 +/- 0.01 vs. d 14, 0.084 +/-
      0.01%/h) (P < 0.05, d 0 vs. d 5). Androgen receptor expression was significantly
      increased in older men by d 14, but had not increased in older women. No change
      was noted in IGF-I expression in either group. We conclude that the skeletal
      muscle of older women and men responds to androgen administration, although the
      time course of anabolism appears to be gender specific.

PMID- 16895964
TI  - Changes in insulin sensitivity and glucose and bone metabolism over time in
      patients with asymptomatic primary hyperparathyroidism.
AB  - OBJECTIVE: The clinical profile of asymptomatic primary hyperparathyroidism
      (PHPT) has shifted from a symptomatic disorder toward a more subtle, asymptomatic
      state. The lack of knowledge about the natural course of asymptomatic PHPT
      contributes to the controversy regarding the optimal management of these
      patients. The aim of this study is to evaluate the natural course of calcium and
      glucose metabolism abnormalities, insulin sensitivity, and bone mineral density
      (BMD) in subjects with asymptomatic PHPT over 18 months. DESIGN: The study was
      designed as a prospective observational examination of asymptomatic PHPT patients
      at baseline and at 6-month intervals for 18 months. METHODS: Our study examined
      61 patients with asymptomatic PHPT and 80 healthy control subjects matched for
      age, sex, and body mass index. We evaluated calcium metabolism, glucose
      metabolism by oral glucose tolerance test, insulin sensitivity by homeostasis
      model assessment index, and BMD by dual-energy x-ray absorptiometry at distal
      radius, lumbar spine, and femur. RESULTS: Although in asymptomatic PHPT patients,
      homeostasis model assessment index at baseline was slightly higher than in
      controls (3.0 +/- 2.2 vs. 2.2 +/- 1.3; P = 0.035), the prevalence of preexisting
      diabetes mellitus (13.1 vs. 11.3%), undiagnosed impaired fasting glucose (34.4
      vs. 30%), impaired glucose tolerance (13.1 vs. 18.8%), and newly diagnosed
      diabetes mellitus (4.9% vs. 2.5%) was similar. Baseline BMDs (g/cm2) at all three
      sites were not different between two groups. Six-month interval measurements
      showed no change in calcium metabolism parameters including serum calcium,
      phosphorus, 25-hydroxyvitamin D, and 24-h calcium excretion. No significant
      longitudinal adverse changes were noted in glucose metabolism, insulin
      sensitivity, or BMD at any site over the 18-month observation period.
      CONCLUSIONS: Our follow-up of patients with asymptomatic PHPT revealed no
      progression of calcium and glucose metabolism abnormalities, insulin sensitivity,
      and loss of BMD during the 18-month study period.

PMID- 16895965
TI  - Continuous recognition of the elicitor signal for several hours is prerequisite
      for induction of cell death and prolonged activation of signaling events in
      tobacco BY-2 cells.
AB  - To provide insights into the mechanisms by which receptors for pathogenic
      elicitors activate defense signaling, we investigated the duration of cryptogein
      treatment required for induction of various defense responses including
      programmed cell death in synchronized tobacco BY-2 cells. Transient cryptogein
      treatment induced only a rapid and transient phase of oxidative burst and mitogen
      activated protein kinase (MAPK) activation. Prolonged production of *O(2)(-) and
      prolonged activation of MAPKs, as well as accumulation of transcripts of defense
      related genes and cell death, required continuous recognition of cryptogein for
      several hours. In contrast, desensitization was gradually induced in the absence
      of the elicitor.

PMID- 16895966
TI  - ATP, phosphorylation and transcription regulate the mobility of plant splicing
      factors.
AB  - Serine-arginine-rich (SR) proteins, a family of spliceosomal proteins, function
      at multiple steps in the assembly of the spliceosome in non-plant systems.
      Limited studies with metazoan SR splicing factors (ASF/SF2 and SC35) indicated
      that their mobility is not dependent on ATP and phosphorylation. In addition,
      inhibition of transcription slightly increased their mobility. Here, we analyzed
      the mobility of SR45, a plant-specific SR protein with unique domain
      organization, and SR1/SRp34, a plant homolog of metazoan ASF/SF2, using
      fluorescence recovery after photobleaching (FRAP) and fluorescence loss in
      photobleaching (FLIP). Our results show that, in contrast to metazoan SR splicing
      factors, the movement of the plant SR proteins is dependent on ATP,
      phosphorylation and transcription. To understand the underlying mechanism for
      these observations, we carried out mobility analyses with the domain-deletion
      mutants of SR45 in ATP-depleted cells and in the presence of inhibitors of
      transcription or phosphorylation. Our results show that the sensitivity of SR45
      to these inhibitors is conferred by an RNA-recognition motif (RRM) and the serine
      arginine-rich (RS) domain 2. These results provide important insights into the
      mechanisms of plant SR protein movement and suggest fundamental differences in
      the regulation of the mobility of plant and animal SR splicing factors.

PMID- 16895967
TI  - Functional domain mapping of peroxin Pex19p: interaction with Pex3p is essential
      for function and translocation.
AB  - The peroxin Pex19p functions in peroxisomal membrane assembly. Here we mapped
      functional domains of human Pex19p comprising 299 amino acids. Pex19p mutants
      deleted in the C-terminal CAAx farnesylation motif, the C-terminal 38 amino acid
      residues and the N-terminal 11 residues, maintained peroxisome-restoring activity
      in pex19 cells. The sequence 12-261 was essential for re-establishing peroxisome
      activity. Pex19p was partly localized to peroxisomes but mostly localized in the
      cytosol. Pex19p interacted with multiple membrane proteins, including the other
      two membrane biogenesis peroxins, Pex3p and Pex16p, those involved in matrix
      protein import such as Pex14p, Pex13p, Pex10p, and Pex26p, peroxisome
      morphogenesis factor Pex11pbeta, and a PMP70 peroxisome-targeting signal region
      at residues 1-123. In yeast two-hybrid assays, Pex10p and Pex11pbeta interacted
      only with full-length Pex19p. Of various truncated Pex19p variants active in
      translocating to peroxisomes, the mutants with the shortest sequence (residues 12
      73 and 40-131) were localized to peroxisomes and competent in binding to Pex3p.
      Furthermore, membrane peroxins were initially discernible in a cytosolic staining
      pattern in pex19 cells only when co-expressed with Pex19p and were then localized
      to peroxisomes in a temporally differentiated manner. Pex19p probably functions
      as a chaperone for membrane proteins and transports them to peroxisomes by
      anchoring to Pex3p using residues 12-73 and 40-131.

PMID- 16895968
TI  - Non-muscle myosins 2A and 2B drive changes in cell morphology that occur as
      myoblasts align and fuse.
AB  - The interaction of non-muscle myosins 2A and 2B with actin may drive changes in
      cell movement, shape and adhesion. To investigate this, we used cultured
      myoblasts as a model system. These cells characteristically change shape from
      triangular to bipolar when they form groups of aligned cells. Antisense
      oligonucleotide knockdown of non-muscle myosin 2A, but not non-muscle myosin 2B,
      inhibited this shape change, interfered with cell-cell adhesion, had a minor
      effect on tail retraction and prevented myoblast fusion. By contrast, non-muscle
      myosin 2B knockdown markedly inhibited tail retraction, increasing cell length by
      over 200% by 72 hours compared with controls. In addition it interfered with
      nuclei redistribution in myotubes. Non-muscle myosin 2C is not involved as
      western analysis showed that it is not expressed in myoblasts, but only in
      myotubes. To understand why non-muscle myosins 2A and 2B have such different
      roles, we analysed their distributions by immuno-electron microscopy, and found
      that non-muscle myosin 2A was more tightly associated with the plasma membrane
      than non-muscle myosin 2B. This suggests that non-muscle myosin 2A is more
      important for bipolar shape formation and adhesion owing to its preferential
      interaction with membrane-associated actin, whereas the role of non-muscle myosin
      2B in retraction prevents over-elongation of myoblasts.

PMID- 16895969
TI  - Recruitment dynamics of GAK and auxilin to clathrin-coated pits during
      endocytosis.
AB  - Cyclin G-associated kinase (GAK), the ubiquitous form of the neuronal-specific
      protein auxilin 1, is an essential cofactor for Hsc70-dependent uncoating of
      clathrin-coated vesicles. Total internal reflectance microscopy was used to
      determine the timing of GAK binding relative to dynamin and clathrin binding
      during invagination of clathrin-coated pits. Following transient recruitment of
      dynamin to the clathrin puncta, large amounts of GAK are transiently recruited.
      GAK and clathrin then disappear from the evanescent field as the pit invaginates
      from the plasma membrane and finally these proteins disappear from the
      epifluorescence field, probably as the clathrin is uncoated from the budded
      vesicles by Hsc70. The recruitment of GAK is dependent on its PTEN-like domain,
      which we found binds to phospholipids. This suggests that interaction with
      phospholipids is essential for recruitment of GAK and, in turn, Hsc70, but Hsc70
      recruitment alone might not be sufficient to induce irreversible clathrin
      uncoating. When budding of clathrin-coated pits is inhibited by actin
      depolymerization, there is repeated flashing of GAK on the clathrin-coated pit
      but neither scission nor irreversible uncoating occur. Therefore, budding as well
      as synchronous recruitment of GAK might be required for irreversible clathrin
      uncoating.

PMID- 16895970
TI  - Redundant roles of Sox17 and Sox18 in postnatal angiogenesis in mice.
AB  - Sox7, Sox17 and Sox18 constitute group F of the Sox family of HMG box
      transcription factor genes. Dominant-negative mutations in Sox18 underlie the
      cardiovascular defects observed in ragged mutant mice. By contrast, Sox18(-/-)
      mice are viable and fertile, and display no appreciable anomaly in their
      vasculature, suggesting functional compensation by the two other SoxF genes.
      Here, we provide direct evidence for redundant function of Sox17 and Sox18 in
      postnatal neovascularization by generating Sox17(+/-) -Sox18(-/-) double mutant
      mice. Whereas Sox18(-/-) and Sox17(+/-) -Sox18(+/-) mice showed no vascular
      defects, approximately half of the Sox17(+/-) -Sox18(-/-) pups died before
      postnatal day 21 (P21). They showed reduced neovascularization in the liver
      sinusoids and kidney outer medulla vasa recta at P7, which most likely caused the
      ischemic necrosis observed by P14 in hepatocytes and renal tubular epithelia.
      Those that survived to adulthood showed similar, but milder, vascular anomalies
      in both liver and kidney, and females were infertile with varying degrees of
      vascular abnormalities in the reproductive organs. These anomalies corresponded
      with sites of expression of Sox7 and Sox17 in the developing postnatal
      vasculature. In vitro angiogenesis assays, using primary endothelial cells
      isolated from the P7 livers, showed that the Sox17(+/-) -Sox18(-/-) endothelial
      cells were defective in endothelial sprouting and remodeling of the vasculature
      in a phenotype-dependent manner. Therefore, our findings indicate that Sox17 and
      Sox18, and possibly all three SoxF genes, are cooperatively involved in mammalian
      vascular development.

PMID- 16895971
TI  - Activation of Tie2 by angiopoietin-1 and angiopoietin-2 results in their release
      and receptor internalization.
AB  - The receptor tyrosine kinase Tie2 is highly expressed in endothelial cells and is
      crucial for angiogenesis and vascular maintenance. The ligands for Tie2 are the
      angiopoietins, of which angiopoietin-1 and angiopoietin-2 have been the most
      studied. Angiopoietin-1 has been characterized as the primary activating ligand
      for Tie2 whereas the role of angiopoietin-2 remains controversial; activating
      Tie2 in some studies and inhibiting Tie2 in others. Our studies were aimed at
      understanding the regulation of Tie2 in endothelial cells by angiopoietin-1 and
      angiopoietin-2 and revealed that both ligands activated Tie2 in a concentration
      dependent manner. Angiopoietin-2 was considerably weaker at activating Tie2
      compared with angiopoietin-1 suggesting that angiopoietin-2 may be a partial
      agonist. Activation of Tie2 by these ligands resulted in differential turnover of
      the receptor where binding of angiopoietin-1, and to a lesser extent angiopoietin
      2, induced rapid internalization and degradation of Tie2. Furthermore, our
      binding studies demonstrate that both ligands are differentially released from
      the endothelial cell surface after receptor activation and accumulate in the
      surrounding medium. Altogether, these data begin our understanding of the
      regulation of Tie2 and the activity of the angiopoietins after engaging the
      endothelial cell surface.

PMID- 16895972
TI  - Genetic analysis of the stress-responsive adrenocortical axis.
AB  - The underlying genetic components contributing to individual variability in
      functions of the stress-responsive hypothalamic-pituitary-adrenal (HPA) axis are
      poorly understood. To determine genetic loci mediating three aspects of the
      adrenocortical function, we conducted a quantitative trait locus (QTL) analysis
      in the segregating F2 generation of a Wistar Kyoto (WKY) x Fischer 344 (F344)
      cross, two inbred rat strains that differ in several HPA axis measures. The
      following three components of adrenocortical function are known to be regulated
      by different mechanisms that are mediated via suprahypothalamic, hypothalamic,
      pituitary, and intra-adrenal influences: basal plasma corticosterone (Cort)
      levels, plasma Cort response to a 10-min restraint stress, and adrenal weight.
      Genome scans identified a complex genetic architecture for the basal Cort
      phenotype, including sex and maternal lineage effects. Pairwise interactions were
      also identified for this trait. We identified three significant and two
      suggestive QTLs for stress Cort, along with two pairs of interacting loci for
      this trait. Four highly significant and two suggestive loci were identified for
      adrenal weight, with no interacting loci. In contrast to basal Cort, no sex- or
      lineage-dependent QTL were identified for stress Cort or adrenal weight, despite
      the large sex differences in these phenotypes. We identified three nucleotide
      alterations in an obvious candidate gene mapped to the most significant QTL for
      stress Cort, Cort-binding globulin (CBG), one of which is known to alter CBG
      binding. This analysis confirms that three separate traits regulated by the HPA
      axis are controlled by multiple, but mainly nonoverlapping, QTLs.

PMID- 16895973
TI  - Immature monocytes from G-CSF-mobilized peripheral blood stem cell collections
      carry surface-bound IL-10 and have the potential to modulate alloreactivity.
AB  - Production of the anti-inflammatory cytokine IL-10 by monocytes has been
      implicated as a probable negative regulator of graft-versus-host disease (GvHD)
      in patients undergoing allogeneic stem cell transplants (SCT). Monocytes from G
      CSF-mobilized peripheral blood stem cell (gmPBSC) collections have been reported
      to produce more IL-10 than unmobilized monocytes in response to proinflammatory
      factors such as LPS. Why this should occur is unclear. In this study, monocyte
      phenotype and IL-10 localization and release were investigated in PB mononuclear
      cells (MNC) from 27 healthy donors mobilized for allogeneic SCT and from 13
      patients with hematological malignancies mobilized for autologous SCT. All
      isolates contained elevated total percentages of monocytes in comparison with
      unmobilized PB, a high proportion of which displayed an immature phenotype.
      Stimulation of gmPB MNC with an inflammatory stimulus [fixed Staphylococcus
      aureus cells (SAC)] induced rapid up-regulation of CD14, indicating conversion to
      mature status. Localization studies indicated that IL-10 was predominantly
      present, bound on the surface of CD64(+)/CD14(low/neg) immature monocytes.
      Inflammatory stimuli (LPS, polyinosinic:polycytidylic acid, or SAC) induced
      release of variable quantities of IL-10 from the cell surface. MNC, separated
      into surface IL-10-positive or -negative fractions, differed in their ability to
      stimulate alloreactivity in MLR, and IL-10(+) MNC induced significantly lower
      levels of proliferation than IL-10(-) MNC. Thus, the subset of immature monocytes
      carrying surface-bound IL-10 in gmPB has the potential to modulate alloreactivity
      and GvHD after allogeneic SCT through cell-to-cell contact and released IL-10.

PMID- 16895974
TI  - Innate immune response to Francisella tularensis is mediated by TLR2 and caspase
      1 activation.
AB  - Francisella tularensis, a gram-negative, facultative, intracellular bacterium, is
      the etiologic agent of tularemia and a category A bioterrorism agent. Little is
      known about the mechanism of pathogenesis of tularemia. In this paper, we
      describe the interaction of the live vaccine strain of F. tularensis with the
      innate immune system. We have found that in human and mouse dendritic cells, F.
      tularensis elicited a powerful inflammatory response, characterized by production
      of a number of cytokines and chemokines. Using cells derived from TLR2-deficient
      mice and in vitro transfection assays, we demonstrated that this response was
      mediated by TLR2 and did not require the LPS-binding protein. F. tularensis
      appeared to activate TLR2/TLR1 and TLR2/TLR6 heterodimers. IL-1beta secretion, a
      reflection of caspase-1 activation, was induced by live but not heat-killed F.
      tularensis, despite the fact that both forms of the bacterium equally induced the
      IL-1beta transcript. Our results identified activation of TLR2 and caspase-1 as
      the two main cellular pathways responsible for the inflammatory response to F.
      tularensis.

PMID- 16895975
TI  - Effects of 17beta-estradiol and flutamide on inflammatory response and distant
      organ damage following trauma-hemorrhage in metestrus females.
AB  - We hypothesized that administration of androgen receptors antagonist flutamide
      following trauma-hemorrhage (T-H) in metestrus females will maintain immune
      function and reduce remote organ damage under those conditions. Female B57BL/J6
      mice (metestrus state, 8-12 weeks old) underwent laparotomy and hemorrhagic shock
      (35.0+/-5.0 mmHg for 90 min) and then received 17beta-estradiol (E2; 50 microg/25
      g), flutamide (625 microg/25 g), or E2 + flutamide. Four hours after
      resuscitation, plasma cytokine and chemokine (TNF-alpha, IL-6, IL-10, IFN-gamma,
      and MCP-1) concentrations and their release in vitro by hepatic and pulmonary
      tissue macrophages (M Phi) were determined by flow cytometry. Organ damage was
      assessed by edema formation (wet-to-dry weight ratio) and neutrophil infiltration
      [myeloperoxidase (MPO) activity]. Administration of E2, flutamide, or E2 +
      flutamide following T-H resulted in a significant decrease in systemic TNF-alpha,
      IL-6, and MCP-1 concentrations under those conditions. This was accompanied by
      significantly decreased in vitro TNF-alpha release by Kupffer cells after
      administration of E2, flutamide, or E2 + flutamide. The in vitro release of
      proinflammatory cytokines by alveolar M Phi, however, was reduced significantly
      only by the addition of E2 or E2 + flutamide but not by the addition of
      flutamide. A significant decrease in pulmonary and hepatic edema formation as
      well as neutrophil infiltration in the lung was observed after E2, flutamide and
      E2 + flutamide administration. In contrast, hepatic neutrophil infiltration was
      only significantly reduced following E2 and E2 + flutamide administration. Thus,
      although flutamide does not produce synergistic, salutary effects with E2, its
      administration in females following T-H also produces salutary effects on the
      immune and organ function, similar to E2 administration under those conditions.

PMID- 16895976
TI  - Increased estrogen sulfation of estradiol 17beta-D-glucuronide in metastatic
      tumor rat livers.
AB  - Changes in the disposition of estradiol 17beta-d-glucuronide (E(2)17G), a
      substrate of the organic anion-transporting polypeptide family (Oatp) and
      multidrug resistance-associated protein 2 (Mrp2), were examined in livers of male
      Wag/Rij rats that were injected with CC531 cells intraportally to induce
      metastatic tumors (n = 5) or with phosphate-buffered saline for sham-operated
      controls (n = 4). Multiple indicator dilution, single-pass liver perfusions
      revealed extremely high influx clearances of [(3)H]E(2)17G (>190 ml/min) in both
      groups. In recirculating liver perfusions, [(3)H]E(2)17G decayed
      monoexponentially in the reservoir perfusate, and the total (9.19 +/- 1.33 versus
      8.18 +/- 0.94 ml/min) and biliary (4.94 +/- 1.07 versus 4.60 +/- 0.86 ml/min)
      clearances were similar in both groups (P > 0.05). The metabolic clearance of
      E(2)17G was higher in the tumor group (4.60 +/- 0.64 versus 3.23 +/- 0.23 ml/min,
      P < 0.05). E(2)3S17G, the 3-sulfate metabolite, whose identity was confirmed by
      mass spectrometry, appeared only in bile and not perfusate. Liver microsomal
      incubations of E(2)3(35)S17G and [(3)H]estrone sulfate revealed similar sulfatase
      activities between the tumor and sham livers, albeit the activities were much
      lower for E(2)3(35)S17G. Oatp1a1 and Oatp1b2 protein expression in liver membrane
      fragments was reduced by 42% and 38%, respectively, whereas that of cytosolic
      estrogen sulfotransferase (Sult1e1) was significantly increased (41%) with tumor
      (P < 0.05). All of the observations were captured by modeling. From modeling, we
      showed that reduction of the high influx clearance (546 to 283 ml/min) failed to
      lower the total clearance of E(2)17G, whereas up-regulation of Sult1e1 increased
      the E(2)17G sulfation clearance (2.56 to 3.69 ml/min) in livers with metastatic
      tumors.

PMID- 16895977
TI  - Nitric oxide production by the vacuolar-type (H+)-ATPase inhibitors bafilomycin
      A1 and concanamycin A and its possible role in apoptosis in RAW 264.7 cells.
AB  - In the mouse leukemic monocyte cell line RAW 264.7, the vacuolar-type (H(+))
      ATPase (V-ATPase) inhibitors bafilomycin A1 and concanamycin A induced nitric
      oxide (NO) production through the expression of inducible nitric-oxide synthase
      mRNA and its protein and decreased cell growth and survival as determined by 3
      (4,5-dimethyl(thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay.
      Bafilomycin A1 and concanamycin A activated nuclear factor (NF)-kappaB and
      activator protein-1 and decreased the level of IkappaB-alpha and increased that
      of phosphorylated c-Jun N-terminal kinase (JNK). NO production induced by these V
      ATPase inhibitors was suppressed by the NF-kappaB inhibitor Bay 11-7082 [(E)3-[(4
      methylphenyl)sulfonyl])-2-propenenitrile] and the JNK inhibitor SP600125
      [anthra[1,9-cd]pyrazol-6(2H)-one] in parallel with the partial alleviation of the
      V-ATPase inhibitor-induced decrease in MTT response. The Na(+),K(+)-ATPase
      inhibitor dibucaine and the F-ATPase inhibitor oligomycin did not induce NO
      production at which concentrations the MTT response was decreased. The NO donor S
      nitroso-N-acetyl-dl-penicillamine further lowered the V-ATPase inhibitor-induced
      decrease in the MTT response, and the NO scavenger 2-(4-carboxyphenyl)-4,4,5,5
      tetramethylimidazoline-1-oxyl-3-oxide, sodium salt (carboxy-PTIO) alleviated it
      partially. Mitochondrial depolarization, an index of apoptosis, was induced by
      bafilomycin A1 and concanamycin A. On treatment with the nitric-oxide synthase
      inhibitor N(G)-monomethyl-l-arginine acetate, the disruption of mitochondrial
      membrane potential induced by bafilomycin A1 and concanamycin A was alleviated
      partially in parallel with the decrease in NO production. Carboxy-PTIO also
      alleviated it partially. Our findings suggest that the V-ATPase inhibitors
      bafilomycin A1 and concanamycin A similarly induce NO production and the newly
      produced NO participates partially in the V-ATPase inhibitor-induced apoptosis in
      RAW 264.7 cells.

PMID- 16895978
TI  - Molecular determinants in the transport of a bile acid-derived diagnostic agent
      in tumoral and nontumoral cell lines of human liver.
AB  - Contrast-enhanced magnetic resonance imaging (CE-MRI) is a valuable technique for
      the diagnosis of liver diseases. As gadocoletic acid trisodium salt (B22956/1), a
      new contrast agent showing high biliary excretion, may be potentially
      advantageous in hepatobiliary imaging, the aim of the study was to investigate
      the molecular mechanisms of hepatic transport of the B22956 ion in a cellular
      model of hepatic tumor. B22956 ion uptake was measured in tumoral (HepG2) and
      nontumoral (Chang liver) hepatic cell lines. Absolute quantitative real-time
      reverse transcriptase (RT)-polymerase chain reaction (PCR) analyses, using cloned
      PCR products as standards, were performed on total RNA of both cell lines and
      normal liver to evaluate the transcription of 12 transport genes: SLCO1A2,
      SLCO2B1, SLCO1B1, SLCO3A1, SLCO4A1, SLCO1B3, SLC22A7, SLC22A8, SLC22A1, SLC10A1,
      SLC15A1, and SLC15A2. B22956 transport was more efficient in Chang liver than in
      HepG2 cells and was inhibited by cholecystokinin-8, a specific substrate of
      OATP1B3. Real-time RT-PCR analyses revealed different transcription profiles in
      the tumoral and nontumoral cell lines. Compared with normal liver, the expression
      of SLCO1B1, SLCO3A1, and SLCO1B3 was greatly repressed in HepG2 cells, whereas
      SLCO2B1, SLC22A7, and SLC22A8 expression was either maintained or increased. On
      the contrary, in Chang liver cells, SLC22A7 and SLC22A8 genes were undetectable,
      whereas the expression of SLCO3A1, SLCO4A1, and SLCO1B3 was similar to normal
      liver. Transport studies and gene expression analyses indicated that B22956 ion
      is a good substrate to the liver-specific OATP1B3, reported to be poorly
      expressed or absent in human liver tumors. Therefore, B22956 may be helpful in
      detecting hepatic neoplastic lesions by CE-MRI.

PMID- 16895979
TI  - The mechanism of carbamazepine aggravation of absence seizures.
AB  - Carbamazepine (CBZ) aggravates many generalized seizures types, particularly
      absence seizures, but the mechanisms underlying this are poorly understood. GABA
      signaling within the reticular nucleus (Rt) and the ventrobasal complex (VB) of
      the thalamus is critical to the neurophysiology of absence seizures. The
      hypothesis that CBZ aggravates absence seizures by acting at the VB thalamus via
      a GABA(A) receptor-mediated mechanism was investigated in a genetic rat model,
      generalized absence epilepsy rats from Strasbourg (GAERS). Seizure activity was
      quantified by a 90-min electroencephalogram recording postdrug injection.
      Intracerebroventricular injections of CBZ (15 microg in 4 microl) resulted in
      seizure aggravation versus vehicle treatment, with a mean increase in seizure
      time of 40%. This indicates that CBZ acts directly, rather than via a metabolite,
      on the brain to aggravate seizures. Seizure aggravation also occurred following
      bilateral microinjection of CBZ (0.75 microg in 0.2 microl) into the VB (53%) but
      not following injection into the Rt (-9%). However, seizure aggravation was
      blocked when the GABA(A) receptor antagonist, bicuculline (BIC, 0.04 microg in
      0.2 microl), was coinjected with CBZ into the VB. Injection of BIC alone (versus
      vehicle) into the VB also blocked seizure aggravation following systemic
      administration of CBZ (15 mg/kg i.p.). In vitro studies in Xenopus oocytes
      expressing recombinant GABA(A) receptors demonstrated that CBZ produced a dose
      dependent potentiation of the GABA current at a physiological relevant
      concentration range (1-100 microM). These data demonstrate that CBZ acts at the
      VB thalamus to aggravate absence seizures in GAERS and that activation of GABA(A)
      receptors is critical to this effect.

PMID- 16895980
TI  - TAF4 nucleates a core subcomplex of TFIID and mediates activated transcription
      from a TATA-less promoter.
AB  - Activator-dependent recruitment of TFIID initiates formation of the
      transcriptional preinitiation complex. TFIID binds core promoter DNA elements and
      directs the assembly of other general transcription factors, leading to binding
      of RNA polymerase II and activation of RNA synthesis. How TATA box-binding
      protein (TBP) and the TBP-associated factors (TAFs) are assembled into a
      functional TFIID complex with promoter recognition and coactivator activities in
      vivo remains unknown. Here, we use RNAi to knock down specific TFIID subunits in
      Drosophila tissue culture cells to determine which subunits are most critical for
      maintaining stability of TFIID in vivo. Contrary to expectations, we find that
      TAF4 rather than TBP or TAF1 plays the most critical role in maintaining
      stability of the complex. Our analysis also indicates that TAF5, TAF6, TAF9, and
      TAF12 play key roles in stability of the complex, whereas TBP, TAF1, TAF2, and
      TAF11 contribute very little to complex stability. Based on our results, we
      propose that holo-TFIID comprises a stable core subcomplex containing TAF4, TAF5,
      TAF6, TAF9, and TAF12 decorated with peripheral subunits TAF1, TAF2, TAF11, and
      TBP. Our initial functional studies indicate a specific and significant role for
      TAF1 and TAF4 in mediating transcription from a TATA-less, downstream core
      promoter element (DPE)-containing promoter, whereas a TATA-containing, DPE-less
      promoter was far less dependent on these subunits. In contrast to both TAF1 and
      TAF4, RNAi knockdown of TAF5 had little effect on transcription from either class
      of promoter. These studies significantly alter previous models for the assembly,
      structure, and function of TFIID.

PMID- 16895981
TI  - Glycoproteomic probes for fluorescent imaging of fucosylated glycans in vivo.
AB  - Glycomics is emerging as a new field for the biology of complex glycoproteins and
      glycoconjugates. The lack of versatile glycan-labeling methods has presented a
      major obstacle to visualizing at the cellular level and studying glycoconjugates.
      To address this issue, we developed a fluorescent labeling technique based on the
      Cu(I)-catalyzed [3 + 2] cycloaddition, or click chemistry, which allows rapid,
      versatile, and specific covalent labeling of cellular glycans bearing azide
      groups. The method entails generating a fluorescent probe from a nonfluorescent
      precursor, 4-ethynyl-N-ethyl-1,8-naphthalimide, by clicking the fluorescent
      trigger, the alkyne at the 4 position, with an azido-modified sugar. Using this
      click-activated fluorescent probe, we demonstrate incorporation of an azido
      containing fucose analog into glycoproteins via the fucose salvage pathway.
      Distinct fluorescent signals were observed by flow cytometry when cells treated
      with 6-azidofucose were labeled with the click-activated fluorogenic probe or
      biotinylated alkyne. The intracellular localization of fucosylated
      glycoconjugates was visualized by using fluorescence microscopy. This technique
      will allow dynamic imaging of cellular fucosylation and facilitate studies of
      fucosylated glycoproteins and glycolipids.

PMID- 16895982
TI  - Calbindin D(9k) knockout mice are indistinguishable from wild-type mice in
      phenotype and serum calcium level.
AB  - Since the discovery of calbindin D(9k), its role in intestinal calcium absorption
      has remained unsettled. Further, a wide distribution of calbindin D(9k) among
      tissues has argued for its biological importance. We discovered a frameshift
      deletion in the calbindin D(9k) gene in an ES cell line, E14.1, that originated
      from 129/OlaHsd mice. We produced mice with the mutant calbindin D(9k) gene by
      injecting the E14.1 ES cell subline into the C57BL/6 host blastocysts and proved
      that these mice lack calbindin D(9k) protein. Calbindin D(9k) knockout mice were
      indistinguishable from wild-type mice in phenotype, were able to reproduce, and
      had normal serum calcium levels. Thus, calbindin D(9k) is not required for
      viability, reproduction, or calcium homeostasis.

PMID- 16895983
TI  - Linkage between cellular communications, energy utilization, and proliferation in
      metastatic neuroendocrine cancers.
AB  - To identify metabolic features that support the aggressive behavior of human
      neuroendocrine (NE) cancers, we examined metastatic prostate NE tumors and
      derived prostate NE cancer (PNEC) cell lines from a transgenic mouse model using
      a combination of magic angle spinning NMR spectroscopy, in silico predictions of
      biotransformations that observed metabolites may undergo, biochemical tests of
      these predictions, and electrophysiological/calcium imaging studies. Malignant NE
      cells undergo excitation and increased proliferation when their GABA(A),
      glutamate, and/or glycine receptors are stimulated, use glutamate and GABA as
      substrates for NADH biosynthesis, and produce propylene glycol, a precursor of
      pyruvate derived from glycine that increases levels of circulating free fatty
      acids through extra-NE cell effects. Treatment of nude mice containing PNEC tumor
      xenografts with (i) amiloride, a diuretic that inhibits Abp1, an enzyme involved
      in NE cell GABA metabolism, (ii) carbidopa, an inhibitor of dopa decarboxylase
      which functions upstream of Abp1, plus (iii) flumazenil, a benzodiazepine
      antagonist that binds to GABA(A) receptors, leads to significant reductions in
      tumor growth. These findings may be generally applicable: GeneChip data sets from
      471 human neoplasms revealed that components of GABA metabolic pathways,
      including ABP1, exhibit statistically significant increases in their expression
      in NE and non-NE cancers.

PMID- 16895984
TI  - Monitoring molecular dynamics using coherent electrons from high harmonic
      generation.
AB  - We report a previously undescribed spectroscopic probe that makes use of
      electrons rescattered during the process of high-order harmonic generation. We
      excite coherent vibrations in SF(6) using impulsive stimulated Raman scattering
      with a short laser pulse. A second, more intense laser pulse generates high-order
      harmonics of the fundamental laser, at wavelengths of approximately 20-50 nm. The
      high-order harmonic yield is observed to oscillate, at frequencies corresponding
      to all of the Raman-active modes of SF(6), with an asymmetric mode most visible.
      The data also show evidence of relaxation dynamics after impulsive excitation of
      the molecule. Theoretical modeling indicates that the high harmonic yield should
      be modulated by both Raman and infrared-active vibrational modes. Our results
      indicate that high harmonic generation is a very sensitive probe of vibrational
      dynamics and may yield more information simultaneously than conventional
      ultrafast spectroscopic techniques. Because the de Broglie wavelength of the
      recolliding electron is on the order of interatomic distances, i.e.,
      approximately 1.5 A, small changes in the shape of the molecule lead to large
      changes in the high harmonic yield. This work therefore demonstrates a previously
      undescribed spectroscopic technique for probing ultrafast internal dynamics in
      molecules and, in particular, on the chemically important ground-state potential
      surface.

PMID- 16895986
TI  - Solute-induced retardation of water dynamics probed directly by terahertz
      spectroscopy.
AB  - The dynamics of water surrounding a solute is of fundamental importance in
      chemistry and biology. The properties of water molecules near the surface of a
      bio-molecule have been the subject of numerous, sometimes controversial
      experimental and theoretical studies, with some suggesting the existence of
      rather rigid water structures around carbohydrates and proteins [Pal, S. K.,
      Peon, J., Bagchi, B. and Zewail A. H. (2002) J. Phys. Chem. B 106, 12376-12395].
      Hydrogen bond rearrangement in water occurs on the picosecond time scale, so
      relevant experiments must access these times. Here, we show that terahertz
      spectroscopy can directly investigate hydration layers. By a precise measurement
      of absorption coefficients between 2.3 THz and 2.9 THz we could determine the
      size and the characteristics of the hydration shell. The hydration layer around a
      carbohydrate (lactose) is determined to extend to 5.13 +/- 0.24 A from the
      surface corresponding to approximately 123 water molecules beyond the first
      solvation shell. Accompanying molecular modeling calculations support this result
      and provide a microscopic visualization. Terahertz spectroscopy is shown to probe
      the collective modes in the water network. The observed increase of the terahertz
      absorption of the water in the hydration layer is explained in terms of coherent
      oscillations of the hydration water and solute. Simulations also reveal a slowing
      down of the hydrogen bond rearrangement dynamics for water molecules near
      lactose, which occur on the picosecond time scale. The present study demonstrates
      that terahertz spectroscopy is a sensitive tool to detect solute-induced changes
      in the water network.

PMID- 16895985
TI  - A Ca(2)+ signaling pathway regulates a K(+) channel for low-K response in
      Arabidopsis.
AB  - Nutrient sensing is critical for plant adaptation to the environment. Because of
      extensive farming and erosion, low content of mineral nutrients such as potassium
      (K(+)) in soils becomes a limiting factor for plant growth. In response to low-K
      conditions, plants enhance their capability of K(+) uptake through an unknown
      signaling mechanism. Here we report the identification of a Ca(2+)-dependent
      pathway for low-K response in Arabidopsis. We are not aware of any other example
      of a molecular pathway for a nutrient response in plants. Earlier genetic
      analyses revealed three genes encoding two Ca(2+) sensors (CBL1 and CBL9) and
      their target protein kinase (CIPK23) to be critical for plant growth on low-K
      media and for stomatal regulation, indicating that these calcium signaling
      components participate in the low-K response and turgor regulation. In this
      study, we show that the protein kinase CIPK23 interacted with, and
      phosphorylated, a voltage-gated inward K(+) channel (AKT1) required for K(+)
      acquisition in Arabidopsis. In the Xenopus oocyte system, our studies showed that
      interacting calcium sensors (CBL1 and CBL9) together with target kinase CIPK23,
      but not either component alone, activated the AKT1 channel in a Ca(2+)-dependent
      manner, connecting the Ca(2+) signal to enhanced K(+) uptake through activation
      of a K(+) channel. Disruption of both CBL1 and CBL9 or CIPK23 gene in Arabidopsis
      reduced the AKT1 activity in the mutant roots, confirming that the Ca(2+)-CBL
      CIPK pathway functions to orchestrate transporting activities in planta according
      to external K(+) availability.

PMID- 16895988
TI  - West Nile virus in complex with the Fab fragment of a neutralizing monoclonal
      antibody.
AB  - Flaviviruses, such as West Nile virus (WNV), are significant human pathogens. The
      humoral immune response plays an important role in the control of flavivirus
      infection and disease. The structure of WNV complexed with the Fab fragment of
      the strongly neutralizing mAb E16 was determined to 14.5-Angstrom resolution with
      cryo-electron microscopy. E16, an antibody with therapeutic potential, binds to
      domain III of the WNV envelope glycoprotein. Because of steric hindrance, Fab E16
      binds to only 120 of the 180 possible binding sites on the viral surface. Fitting
      of the previously determined x-ray structure of the Fab-domain III complex into
      the cryo-electron microscopy density required a change of the elbow angle between
      the variable and constant domains of the Fab. The structure suggests that the E16
      antibody neutralizes WNV by blocking the initial rearrangement of the E
      glycoprotein before fusion with a cellular membrane.

PMID- 16895987
TI  - Nonobese diabetic mice express aspects of both type 1 and type 2 diabetes.
AB  - Before the onset of autoimmune destruction, type 1 diabetic patients and an
      animal model, the nonobese diabetic (NOD) mouse, show morphological and
      functional abnormalities in target organs, which may act as inciting events for
      leukocyte infiltration. To better understand these abnormalities, but without the
      complications associated with lymphocytic infiltrates, we examined genes
      expressed in autoimmune target tissues of NOD/severe combined immunodeficient
      (scid) mice and of autoimmune-resistant C57BL/6/scid mice. Our results suggest
      that the NOD genetic background may predispose them to diabetic complications,
      including insulin resistance in the absence of high circulating glucose levels
      and without autoimmune destruction of their beta cells. Several of these genes
      lie within known type 1 and 2 diabetes loci. These data suggest that the NOD
      mouse may be a good candidate to study an interface between type 1 and type 2
      diabetes.

PMID- 16895989
TI  - Nature designs tough collagen: explaining the nanostructure of collagen fibrils.
AB  - Collagen is a protein material with superior mechanical properties. It consists
      of collagen fibrils composed of a staggered array of ultra-long tropocollagen
      (TC) molecules. Theoretical and molecular modeling suggests that this natural
      design of collagen fibrils maximizes the strength and provides large energy
      dissipation during deformation, thus creating a tough and robust material. We
      find that the mechanics of collagen fibrils can be understood quantitatively in
      terms of two critical molecular length scales chi(S) and chi(R) that characterize
      when (i) deformation changes from homogeneous intermolecular shear to propagation
      of slip pulses and when (ii) covalent bonds within TC molecules begin to
      fracture, leading to brittle-like failure. The ratio chi(S)/chi(R) indicates
      which mechanism dominates deformation. Our modeling rigorously links the chemical
      properties of individual TC molecules to the macroscopic mechanical response of
      fibrils. The results help to explain why collagen fibers found in nature consist
      of TC molecules with lengths in the proximity of 300 nm and advance the
      understanding how collagen diseases that change intermolecular adhesion
      properties influence mechanical properties.

PMID- 16895990
TI  - Resonance Raman spectroscopy of chloroperoxidase compound II provides direct
      evidence for the existence of an iron(IV)-hydroxide.
AB  - We report direct evidence for the existence of an iron(IV)-hydroxide. Resonance
      Raman measurements on chloroperoxidase compound II (CPO-II) reveal an isotope
      ((18)O and (2)H)-sensitive band at nu(Fe-O) = 565 cm(-1). Preparation of CPO-II
      in H(2)O using H(2)(18)O(2) results in a red-shift of 22 cm(-1), while
      preparation of CPO-II in (2)H(2)O using H(2)O(2) results in a red-shift of 13 cm(
      1). These values are in good agreement with the isotopic shifts predicted (23 and
      12 cm(-1), respectively) for an Fe-OH harmonic oscillator. The measured Fe-O
      stretching frequency is also in good agreement with the 1.82-A Fe-O bond reported
      for CPO-II. A Badger's rule analysis of this distance provides an Fe-O stretching
      frequency of nu(Badger) = 563 cm(-1). We also present X-band electron nuclear
      double resonance (ENDOR) data for cryoreduced CPO-II. Cryogenic reduction (77 K)
      of the EPR-silent Fe(IV)OH center in CPO-II results in an EPR-active Fe(III)OH
      species with a strongly coupled (13.4 MHz) exchangeable proton. Based on
      comparisons with alkaline myoglobin, we assign this resonance to the hydroxide
      proton of cryoreduced CPO-II.

PMID- 16895992
TI  - The structure of the endoribonuclease XendoU: From small nucleolar RNA processing
      to severe acute respiratory syndrome coronavirus replication.
AB  - Small nucleolar RNAs (snoRNAs) play a key role in eukaryotic ribosome biogenesis.
      In most cases, snoRNAs are encoded in introns and are released through the
      splicing reaction. Some snoRNAs are, instead, produced by an alternative pathway
      consisting of endonucleolytic processing of pre-mRNA. XendoU, the
      endoribonuclease responsible for this activity, is a U-specific, metal-dependent
      enzyme that releases products with 2'-3' cyclic phosphate termini. XendoU is
      broadly conserved among eukaryotes, and it is a genetic marker of nidoviruses,
      including the severe acute respiratory syndrome coronavirus, where it is
      essential for replication and transcription. We have determined by
      crystallography the structure of XendoU that, by refined search methodologies,
      appears to display a unique fold. Based on sequence conservation, mutagenesis,
      and docking simulations, we have identified the active site. The conserved
      structural determinants of this site may provide a framework for attempting to
      design antiviral drugs to interfere with the infectious nidovirus life cycle.

PMID- 16895991
TI  - Follicle-stimulating hormone/cAMP regulation of aromatase gene expression
      requires beta-catenin.
AB  - Estrogens profoundly influence the physiology and pathology of reproductive and
      other tissues. Consequently, emphasis has been placed on delineating the
      mechanisms underlying regulation of estrogen levels. Circulating levels of
      estradiol in women are controlled by follicle-stimulating hormone (FSH), which
      regulates transcription of the aromatase gene (CYP19A1) in ovarian granulosa
      cells. Previous studies have focused on two downstream effectors of the FSH
      signal, cAMP and the orphan nuclear receptor steroidogenic factor-1 (NR5A1). In
      this report, we present evidence for beta-catenin (CTNNB1) as an essential
      transcriptional regulator of CYP19A1. FSH induction of select steroidogenic
      enzyme mRNAs, including Cyp19a1, is enhanced by beta-catenin. Additionally, beta
      catenin is present in transcription complexes assembled on the endogenous gonad
      specific CYP19A1 promoter, as evidenced by chromatin immunoprecipitation assays.
      Transient expression and RNAi studies demonstrate that FSH- and cAMP-dependent
      regulation of this promoter is sensitive to alterations in the level of beta
      catenin. The stimulatory effect of beta-catenin is mediated through functional
      interactions with steroidogenic factor-1 that involve four acidic residues within
      its ligand-binding domain, mutation of which attenuates FSH/cAMP-induced Cyp19a1
      mRNA accumulation. Together, these data demonstrate that beta-catenin is
      essential for FSH/cAMP-regulated gene expression in the ovary, identifying a
      central and previously unappreciated role for beta-catenin in estrogen
      biosynthesis, and a potential broader role in other aspects of follicular
      maturation.

PMID- 16895993
TI  - Viral tracing identifies distributed columnar organization in the olfactory bulb.
AB  - Olfactory sensory neurons converge onto glomeruli in the olfactory bulb (OB) to
      form modular information processing units. Similar input modules are organized in
      translaminar columns for other sensory modalities. It has been less clear in the
      OB whether the initial modular organization relates to a columnar structure in
      the deeper layers involved in local circuit processing. To probe synaptic
      connectivity in the OB, we injected a retrograde-specific strain of the
      pseudorabies virus into the rat OB and piriform cortex. The viral-staining
      patterns revealed a striking columnar organization that extended across all
      layers of the OB from the glomeruli to the deep granule cell layer. We
      hypothesize that the columns represent an extension of the glomerular unit.
      Specific patterning was observed, suggesting selective, rather than distance
      dependent, center-surround connectivity. The results provide a previously
      undescribed basis for interpreting the synaptic connections between mitral and
      granule cells within the context of a columnar organization in the OB and have
      implications for olfactory coding and network organization.

PMID- 16895994
TI  - Phosphate acquisition genes in Prochlorococcus ecotypes: evidence for genome-wide
      adaptation.
AB  - The cyanobacterium Prochlorococcus is the numerically dominant phototroph in the
      oligotrophic oceans. This group consists of multiple ecotypes that are
      physiologically and phylogenetically distinct and occur in different abundances
      along environmental gradients. Here we examine adaptations to phosphate (P)
      limitation among ecotypes. First, we used DNA microarrays to identify genes
      involved in the P-starvation response in two strains belonging to different
      ecotypes, MED4 (high-light-adapted) and MIT9313 (low-light-adapted). Most of the
      up-regulated genes under P starvation were unique to one strain. In MIT9313, many
      ribosomal genes were down-regulated, suggesting a general stress response in this
      strain. We also observed major differences in regulation. The P-starvation
      induced genes comprise two clusters on the chromosome, the first containing the P
      master regulator phoB and most known P-acquisition genes and the second, absent
      in MIT9313, containing genes of unknown function. We examined the organization of
      the phoB gene cluster in 11 Prochlorococcus strains belonging to diverse ecotypes
      and found high variability in gene content that was not congruent with rRNA
      phylogeny. We hypothesize that this genome variability is related to differences
      in P availability in the oceans from which the strains were isolated. Analysis of
      a metagenomic library from the Sargasso Sea supports this hypothesis; most
      Prochlorococcus cells in this low-P environment contain the P-acquisition genes
      seen in MED4, although a number of previously undescribed gene combinations were
      observed.

PMID- 16895995
TI  - Model-based analysis of tiling-arrays for ChIP-chip.
AB  - We propose a fast and powerful analysis algorithm, titled Model-based Analysis of
      Tiling-arrays (MAT), to reliably detect regions enriched by transcription factor
      chromatin immunoprecipitation (ChIP) on Affymetrix tiling arrays (ChIP-chip). MAT
      models the baseline probe behavior by considering probe sequence and copy number
      on each array. It standardizes the probe value through the probe model,
      eliminating the need for sample normalization. MAT uses an innovative function to
      score regions for ChIP enrichment, which allows robust P value and false
      discovery rate calculations. MAT can detect ChIP regions from a single ChIP
      sample, multiple ChIP samples, or multiple ChIP samples with controls with
      increasing accuracy. The single-array ChIP region detection feature minimizes the
      time and monetary costs for laboratories newly adopting ChIP-chip to test their
      protocols and antibodies and allows established ChIP-chip laboratories to
      identify samples with questionable quality that might contaminate their data. MAT
      is developed in open-source Python and is available at
      http://chip.dfci.harvard.edu/ approximately wli/MAT. The general framework
      presented here can be extended to other oligonucleotide microarrays and tiling
      array platforms.

PMID- 16895996
TI  - Voltage-dependent conformational changes in human Ca(2+)- and voltage-activated
      K(+) channel, revealed by voltage-clamp fluorometry.
AB  - Large conductance voltage- and Ca(2+)-activated K(+) (BK(Ca)) channels regulate
      important physiological processes such as neurotransmitter release and vascular
      tone. BK(Ca) channels possess a voltage sensor mainly represented by the S4
      transmembrane domain. Changes in membrane potential displace the voltage sensor,
      producing a conformational change that leads to channel opening. By site-directed
      fluorescent labeling of residues in the S3-S4 region and by using voltage clamp
      fluorometry, we have resolved the conformational changes the channel undergoes
      during activation. The voltage dependence of these conformational changes
      (detected as changes in fluorescence emission, fluorescence vs. voltage curves)
      always preceded the channel activation curves, as expected for protein
      rearrangements associated to the movement of the voltage sensor. Extremely slow
      conformational changes were revealed by fluorescent labeling of position 202,
      elicited by a mutual interaction of the fluorophore with the adjacent tryptophan
      203.

PMID- 16895997
TI  - Metabolic profiling reveals a contribution of gut microbiota to fatty liver
      phenotype in insulin-resistant mice.
AB  - Here, we study the intricate relationship between gut microbiota and host
      cometabolic phenotypes associated with dietary-induced impaired glucose
      homeostasis and nonalcoholic fatty liver disease (NAFLD) in a mouse strain
      (129S6) known to be susceptible to these disease traits, using plasma and urine
      metabotyping, achieved by (1)H NMR spectroscopy. Multivariate statistical
      modeling of the spectra shows that the genetic predisposition of the 129S6 mouse
      to impaired glucose homeostasis and NAFLD is associated with disruptions of
      choline metabolism, i.e., low circulating levels of plasma phosphatidylcholine
      and high urinary excretion of methylamines (dimethylamine, trimethylamine, and
      trimethylamine-N-oxide), coprocessed by symbiotic gut microbiota and mammalian
      enzyme systems. Conversion of choline into methylamines by microbiota in strain
      129S6 on a high-fat diet reduces the bioavailability of choline and mimics the
      effect of choline-deficient diets, causing NAFLD. These data also indicate that
      gut microbiota may play an active role in the development of insulin resistance.

PMID- 16895998
TI  - Wolbachia transinfection in Aedes aegypti: a potential gene driver of dengue
      vectors.
AB  - The endosymbiotic bacteria in the genus Wolbachia are capable of inducing a wide
      range of reproductive abnormalities in their hosts, including cytoplasmic
      incompatibility (CI), which could lead to the replacement of uninfected host
      populations with infected ones. Because of this, Wolbachia have attracted
      considerable interest as a potential mechanism for spreading disease-blocking
      transgenes through vector populations. Here we report the establishment of double
      Wolbachia transinfection by direct adult microinjection of Wolbachia from
      naturally double-infected Aedes albopictus to Aedes aegypti, the most important
      mosquito vector of infectious viral diseases, and a mosquito in which natural
      Wolbachia infections are not known to occur. We further demonstrate that
      incomplete CI is induced in these double-transinfected mosquitoes. Comparisons of
      fitness traits between naturally uninfected and transinfected Ae. aegypti lines
      indicated one significant difference in favor of the latter, namely, an increased
      number of eggs laid. Levels of CI expression corresponded to the Wolbachia
      density. There were large differences in relative Wolbachia density between
      reproductive and nonreproductive tissues in both Ae. albopictus and transinfected
      Ae. aegypti, except Malpighian tubule, which implied the preferred establishment
      of Wolbachia within reproductive tissue. Results from a simulation model confirm
      that population replacement by transinfected Ae. aegypti is possible over time.
      The establishment of Wolbachia double infections in Ae. aegypti by direct adult
      microinjection and the demonstration of CI expression in this new host suggest
      that Wolbachia could be experimentally transferred into vector species and could
      also be used as a gene-driving system to genetically manipulate vector
      populations.

PMID- 16895999
TI  - Role for drug transporters beyond tumor resistance: hepatic functional imaging
      and genotyping of multidrug resistance transporters for the prediction of
      irinotecan toxicity.

PMID- 16896000
TI  - Factors associated with outcomes in allogeneic hematopoietic cell transplantation
      with nonmyeloablative conditioning after failed myeloablative hematopoietic cell
      transplantation.
AB  - PURPOSE: Several studies have investigated the feasibility of allogeneic
      hematopoietic cell transplantations (HCTs) after reduced-intensity conditioning
      in patients who experienced relapse after myeloablative HCT. Although most
      studies showed relatively low nonrelapse mortality (NRM) rates and encouraging
      short-term results, it has yet to be defined which patients would benefit most
      from these approaches. PATIENTS AND METHODS: We analyzed data from 147 patients
      with hematologic malignancies who experienced treatment failure with conventional
      autologous (n = 135), allogeneic (n = 10), or syngeneic (n = 2) HCT and were
      treated with HLA-matched related (n = 62) or unrelated (n = 85) grafts after
      conditioning with 2 Gy of total-body irradiation with or without fludarabine.
      RESULTS: Three-year probabilities of NRM, relapse, and overall survival were 32%,
      48%, and 27%, respectively, for related recipients, and 28%, 44%, and 44%,
      respectively, for unrelated recipients. The best outcomes were observed in
      patients with non-Hodgkin's lymphoma, whereas patients with multiple myeloma and
      Hodgkin's disease had worse outcomes as a result of high incidences of relapse
      and progression. Being in partial remission (PR) or complete remission (CR) at
      HCT (P = .002) and developing chronic graft-versus-host disease (GVHD; P = .03)
      resulted in lower risks of relapse and progression. Factors associated with
      better overall survival were PR or CR (P = .01) and lack of comorbidity (P = .03)
      at HCT and absence of acute GVHD after HCT (P = .06). CONCLUSION: Encouraging
      outcomes were seen with allogeneic HCT after nonmyeloablative conditioning in
      selected patients who had experienced relapse after a high-dose HCT, particularly
      in patients with non-Hodgkin's lymphoma. Results with unrelated grafts were
      comparable with results with related grafts.

PMID- 16896001
TI  - Lactate dehydrogenase 5 expression in operable colorectal cancer: strong
      association with survival and activated vascular endothelial growth factor
      pathway--a report of the Tumour Angiogenesis Research Group.
AB  - PURPOSE: Lactate dehydrogenase 5 (LDH-5) regulates, under hypoxic conditions, the
      anaerobic transformation of pyruvate to lactate for energy acquisition. Several
      studies have shown that serum LDH may be an ominous prognostic marker in
      malignant tumors. The clinical significance of tissue LDH-5, however, remains
      largely unexplored. PATIENTS AND METHODS: We investigated the immunohistochemical
      expression of LDH-5 in a series of 128 stage II/III colorectal adenocarcinomas
      treated with surgery alone. In addition, markers of tumor hypoxia (hypoxia
      inducible factor 1 alpha [HIF1alpha]), angiogenesis (vascular endothelial growth
      factor [VEGF] and phosporylated kinase domain receptor [pKDR]/flk-1 receptor) and
      the tumor vascular density (CD31 positive standard vascular density [sVD] and
      pKDR positive activated vascular density [aVD]) were assessed. RESULTS: The
      expression of LDH-5, together with that of HIF1alpha and pKDR, was both nuclear
      and cytoplasmic. Assessment, with minimal interobserver variability, was achieved
      using a previously described scoring system. LDH-5 was significantly associated
      with HIF1alpha (P = .01), aVD (P = .001) and, particularly, with pKDR expression
      in cancer cells (P = .0001). Tissue LDH-5 expression was linked with elevated
      serum LDH levels, but serum levels failed to reflect tissue expression in 71% of
      LDH-5 positive cases. In univariate analysis tissue LDH-5 was associated with
      poor survival (P = .0003, HR 15.1), whereas in multivariate analysis this
      isoenzyme was the strongest independent prognostic factor (P = .0009). VEGF,
      pKDR, aVD, sVD and vascular invasion were all significantly related to
      unfavorable prognosis. CONCLUSION: The immunohistochemical assessment of tissue
      LDH-5 and pKDR provides important prognostic information in operable colorectal
      cancer. The strong association between LDH-5 and pKDR expression would justify
      their use as surrogate markers to screen patients for tyrosine kinase inhibitor
      therapy.

PMID- 16896002
TI  - DNA-repair gene polymorphisms predict favorable clinical outcome among patients
      with advanced squamous cell carcinoma of the head and neck treated with cisplatin
      based induction chemotherapy.
AB  - PURPOSE: Cisplatin kills tumor cells through DNA cross linking. Alterations in
      the function of DNA repair genes may affect DNA repair proficiency and influence
      cancer patients' response to cisplatin. We studied whether single nucleotide
      polymorphisms (SNPs) of DNA repair genes predict the response to cisplatin or
      prognosis in patients with squamous cell carcinoma of the head and neck (SCCHN).
      METHODS: A polymerase chain reaction-restriction fragment length polymorphism
      (RFLP) approach was used to determine the frequency of the SNPs: XPD-Asp312Asn,
      XPD-Lys751Gln, ERCC1-C8092A, and XRCC1-Arg399Gln in DNA from peripheral
      lymphocytes of 103 stage IV SCCHN patients. RESULTS: The frequencies of the
      distinct genotypes were, respectively, for the homozygous common allele,
      heterozygous and homozygous polymorphic variant: 53%, 40%, and 7% for ERCC1; 50%,
      42%, and 8% for XPD-312; 35%, 57%, and 8% for XPD751; and 35%, 51%, and 13% for
      XRCC1. Patients with only common alleles at all the SNPs tested had a median
      overall survival of 5.1 months (range, 4.3 to 6.0 months) as compared with not
      reached for patients with at least one polymorphic variant (P < .001). Estimates
      from Cox's multivariate analysis suggest that the accumulation of each
      polymorphic variant decreases the probability of dying by a factor of 2.1 (P <
      .001; the presence of seven polymorphic variants confers a 175-fold protection).
      The accumulation of polymorphic variants increases by 2.94-fold the probability
      of achieving a complete response to treatment (P = .041). CONCLUSION: Using a
      multivariate model, the presence of polymorphic variants in DNA-repair genes are
      powerful prognosis factors and response to cisplatin predictors among SCCHN
      patients.

PMID- 16896003
TI  - Phase II trial of CHOP chemotherapy followed by tositumomab/iodine I-131
      tositumomab for previously untreated follicular non-Hodgkin's lymphoma: five-year
      follow-up of Southwest Oncology Group Protocol S9911.
AB  - PURPOSE: Advanced follicular lymphoma (FL) is incurable with conventional
      chemotherapy and radiotherapy, and optimal front-line management is
      controversial. This study was performed to determine the efficacy of
      cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy
      followed by tositumomab/iodine I-131 tositumomab. PATIENTS AND METHODS: From 1999
      to 2000, the Southwest Oncology Group (SWOG) conducted a phase II trial (S9911)
      to test a novel new regimen consisting of six cycles of CHOP chemotherapy
      followed 4 to 8 weeks later by tositumomab/iodine I-131 tositumomab in 90
      eligible patients with previously untreated, advanced-stage FL. RESULTS: The
      overall response rate was 91%, including a 69% complete remission (CR) rate.
      After a median follow-up time of 5.1 years, the estimated 5-year overall survival
      (OS) rate was 87%, and the progression-free survival (PFS) rate was 67%. The 5
      year estimates of OS and PFS were each 23% better (absolute difference) than the
      corresponding figures for patients treated on previous SWOG protocols with CHOP
      alone. An analysis according to the Follicular Lymphoma International Prognostic
      Index showed that 21% of patients had high-risk features, 44% had intermediate
      risk features, and 34% had low-risk features. High-risk patients had worse OS
      than lower risk patients (P = .05), but differences in PFS were not statistically
      significant (P = .21). Serial monitoring of the t(14;18) translocation in bone
      marrow by polymerase chain reaction demonstrated that 32 of 38 informative
      patients obtained molecular CRs, including seven patients (18%) after CHOP and 24
      additional patients (63%) after tositumomab/iodine I-131 tositumomab. (The timing
      of conversion of one patient was unclear.) CONCLUSION: A prospective, phase III,
      randomized Intergroup Trial is currently underway comparing the efficacy of the
      promising CHOP + tositumomab/iodine I-131 tositumomab regimen with the efficacy
      of CHOP + rituximab.

PMID- 16896004
TI  - Pharmacogenomic predictor of sensitivity to preoperative chemotherapy with
      paclitaxel and fluorouracil, doxorubicin, and cyclophosphamide in breast cancer.
AB  - PURPOSE: We developed a multigene predictor of pathologic complete response (pCR)
      to preoperative weekly paclitaxel and fluorouracil-doxorubicin-cyclophosphamide
      (T/FAC) chemotherapy and assessed its predictive accuracy on independent cases.
      PATIENTS AND METHODS: One hundred thirty-three patients with stage I-III breast
      cancer were included. Pretreatment gene expression profiling was performed with
      oligonecleotide microarrays on fine-needle aspiration specimens. We developed
      predictors of pCR from 82 cases and assessed accuracy on 51 independent cases.
      RESULTS: Overall pCR rate was 26% in both cohorts. In the training set, 56 probes
      were identified as differentially expressed between pCR versus residual disease,
      at a false discovery rate of 1%. We examined the performance of 780 distinct
      classifiers (set of genes + prediction algorithm) in full cross-validation. Many
      predictors performed equally well. A nominally best 30-probe set Diagonal Linear
      Discriminant Analysis classifier was selected for independent validation. It
      showed significantly higher sensitivity (92% v 61%) than a clinical predictor
      including age, grade, and estrogen receptor status. The negative predictive value
      (96% v 86%) and area under the curve (0.877 v 0.811) were nominally better but
      not statistically significant. The combination of genomic and clinical
      information yielded a predictor not significantly different from the genomic
      predictor alone. In 31 samples, RNA was hybridized in replicate with resulting
      predictions that were 97% concordant. CONCLUSION: A 30-probe set pharmacogenomic
      predictor predicted pCR to T/FAC chemotherapy with high sensitivity and negative
      predictive value. This test correctly identified all but one of the patients who
      achieved pCR (12 of 13 patients) and all but one of those who were predicted to
      have residual disease had residual cancer (27 of 28 patients).

PMID- 16896005
TI  - Phase II trial of CHOP plus rituximab in patients with HIV-associated non
      Hodgkin's lymphoma.
AB  - PURPOSE: To evaluate the safety and efficacy of rituximab adjunction to the
      cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) regimen in
      patients with newly diagnosed AIDS-related non-Hodgkin's lymphoma. PATIENTS AND
      METHODS: HIV-seropositive patients with high-grade lymphoma of B-cell origin were
      eligible if they had no more than one of the following characteristics: CD4 cell
      count less than 100/microL, prior AIDS, or performance status less than 2. This
      multicenter phase II trial evaluated the response rate and disease-free survival
      after six courses of rituximab plus CHOP. Results Sixty-one patients were
      enrolled. All the patients were assessable for safety and 52 were assessable for
      the tumor response after treatment completion. Characteristics of patients were
      median age, 41 years; median CD4 cells, 172/microL; histology, diffuse large B
      cell lymphoma (n = 42), immunoblastic (n = 2), Burkitt lymphoma (n = 16), and
      plasmablastic (n = 1); 42 patients with stage III to IV; International Prognostic
      Index 0 to 1 (n=31), and 2 to 3 (n = 27). Grade 3 or 4 toxicity consisted of
      febrile neutropenia in nine patients, anemia in 16 patients, and thrombocytopenia
      in five patients. Complete remission (CR) or unconfirmed CR was achieved in 40 of
      the 52 assessable patients, partial remission was achieved in five patients, and
      seven patients experienced progression. Forty-three patients were alive after a
      median follow-up of 33 months. The estimated 2-year overall survival rate was 75%
      (95% CI, 64% to 86%). Eighteen patients died: 16 as a result of lymphoma, one as
      a result of infection, and one as a result of encephalitis. CONCLUSION: Rituximab
      adjunction to CHOP produced a CR rate of 77% and a 2-year survival rate of 75% in
      patients with AIDS-related non-Hodgkin's lymphoma, without increasing the risk of
      life-threatening infections.

PMID- 16896006
TI  - Clinical activity of pertuzumab (rhuMAb 2C4), a HER dimerization inhibitor, in
      advanced ovarian cancer: potential predictive relationship with tumor HER2
      activation status.
AB  - PURPOSE: Ovarian cancers (OCs) frequently have HER2 activation in the absence of
      HER2 overexpression. Pertuzumab, a humanized antibody that prevents HER2
      dimerization and inhibits multiple HER-mediated pathways, was studied in a phase
      II, multicenter trial in advanced, refractory OC. PATIENTS AND METHODS: Sixty-one
      patients (cohort 1) with relapsed OC received a loading dose of 840 mg pertuzumab
      intravenously followed by 420 mg every 3 weeks; 62 patients (cohort 2) received
      1,050 mg every 3 weeks. Response rate was the primary end point. Fresh tumor
      biopsies were obtained in cohort 1 to assay for phosphorylated HER2 (pHER2).
      RESULTS: Median age was 57 years and median number of prior chemotherapy regimens
      was five. Fifty-five patients in cohort 1 and 62 patients in cohort 2 were
      assessable for efficacy. There were five partial responses (response rate [RR] =
      4.3%; 95% CI, 1.7% to 9.4%), eight patients (6.8%) with stable disease (SD)
      lasting at least 6 months, and 10 patients with CA-125 reduction of at least 50%
      (includes two partial responses and four patients with SD > or = 6 months; total
      clinical activity, 14.5%). Median progression-free survival (PFS) was 6.6 weeks.
      Eight of 28 tumor biopsies (28.6%) were pHER2+ by enzyme-linked immunosorbent
      assay (ELISA; without gene amplification). Median PFS for pHER2+ patients was
      20.9 weeks (n = 8) versus 5.8 weeks for pHER2- (n = 20; P = .14) and 9.1 weeks
      for unknown pHER2 status (n = 27). Pertuzumab was well tolerated with diarrhea in
      69.1% (11.4% grade 3, no grade 4). Five patients had asymptomatic left
      ventricular ejection fraction decreases to less than 50% (one confirmed by
      central facility). CONCLUSION: Pertuzumab is well tolerated with a RR of 4.3% in
      heavily-pretreated OC patients. Further studies on pHER2 as a diagnostic are
      warranted.

PMID- 16896007
TI  - Relationship of hepatic functional imaging to irinotecan pharmacokinetics and
      genetic parameters of drug elimination.
AB  - PURPOSE: The marked variability of irinotecan (Ir) clearance warrants
      individualized dosing based on hepatic drug handling. The aims of this trial were
      to identify parameters from functional hepatic nuclear imaging (HNI) that
      correlate with (1) Ir pharmacology, and (2) single-nucleotide polymorphisms
      (SNPs) for the ABCB1 (P-glycoprotein) and UGT-1A1 genes, known to influence Ir
      handling. METHODS: Patients underwent genotyping for ABCB1 SNPs and UTUGT-1A1*28
      carriage and HNI with 99mTc-DIDA (acetanilidoiminodiacetic acid)/99mTc-DISIDA
      (disofenin) and MIBI (99mTc-sestamibi) scans, probes for biliary transport
      proteins ABCC1 and -2, and ABCB1 function. HNI data were analyzed by
      noncompartmental and deconvolutional analysis to provide hepatic extraction and
      biliary excretion parameters. Patients received Ir, fluorouracil, and folinic
      acid using a weekly x2, every-3-weeks schedule. Plasma was taken for Ir and SN-38
      analysis on day 1, cycle 1. RESULTS: Of the 21 patients accrued, Ir
      pharmacokinetics data were obtained from 16 patients. 99mTc-DIDA/DISIDA percent
      retention at 1 hour (1-hour RET) correlated to baseline serum bilirubin (P =
      .008). Both 99mTc-DIDA/DISIDA and MIBI 1-hour RET correlated with SN-38 area
      under the curve (AUC; P < .01). On multiple regression analysis, SN-38 AUC = -215
      + 18.68 x bilirubin + 4.27 x MIBI 1-hour RET (P = .009, R2 = 44.2%). HNI
      parameters did not correlate with Ir toxicity or UGT1A1*28 carriage. MIBI
      excretion was prolonged in patients with the ABCB1 exon 26 TT variant allele
      relative to wild-type (P = .015). CONCLUSION: Functional imaging of hepatic
      uptake and excretory pathways may have potential to predict Ir pharmacokinetics.
      Evaluation of a larger cohort as well as polymorphisms in other biliary
      transporters and UGT1A1 alleles is warranted.

PMID- 16896008
TI  - ErbB-3 predicts survival in ovarian cancer.
AB  - BACKGROUND: HER3 (erbB-3) is a member of the epidermal growth factor receptor
      (EGFR) family. After dimerization with other members of the EGFR family several
      signal transduction cascades can be activated, including phosphoinosite 3'-kinase
      (PI3-K)/Akt and extracellular signal-regulated kinase (ERK1/2). Here, we studied
      a possible association between HER3 expression and prognosis in patients with
      ovarian cancer. METHODS: Tumor tissue of 116 consecutive patients diagnosed with
      primary epithelial ovarian cancer between 1986 and 1995 was analyzed
      immunohistochemically for HER3 expression. A possible influence of HER3
      expression on survival was studied by multivariate Cox regression adjusting for
      established clinical prognostic factors. RESULTS: A positive HER3 expression was
      observed in 53.4% of the patients. HER3 expression was associated with decreased
      survival in proportional hazard modeling, including the International Federation
      of Gynecology and Obstetrics (FIGO) stage, histologic grade and type, residual
      disease, and age. After likelihood ratio forward as well as backward selection,
      only HER3 expression (hazard ratio, 1.71; 95% CI, 1.10 to 2.67; P = .018), FIGO
      stage (hazard ratio, 4.78; 95% CI, 1.89 to 12.08; P = .001), residual tumor
      (hazard ratio, 2.69; 95% CI, 1.40 to 5.17; P = .003), and age (hazard ratio,
      2.06; 95% CI, 1.17 to 3.65; P = .013) were found to be significant. Kaplan-Meier
      plots demonstrated a clear influence of HER3 expression on survival time. Median
      survival time was 3.31 years (95% CI, 1.93 to 4.68) for patients with low HER3
      expression, compared with only 1.80 years (95% CI, 0.83 to 2.78) for patients
      with HER3 overexpression (log-rank test P = .0034). CONCLUSION: HER3 may
      represent a new prognostic factor in primary epithelial ovarian cancer. Pending
      validation, exploration of therapeutic strategies to block HER3 could be
      warranted.

PMID- 16896009
TI  - DNA repair pathways in clinical practice: lessons from pediatric cancer
      susceptibility syndromes.
AB  - Human cancers exhibit genomic instability and an increased mutation rate due to
      underlying defects in DNA repair. Cancer cells are often defective in one of six
      major DNA repair pathways, namely: mismatch repair, base excision repair,
      nucleotide excision repair, homologous recombination, nonhomologous endjoining
      and translesion synthesis. The specific DNA repair pathway affected is predictive
      of the kinds of mutations, the tumor drug sensitivity, and the treatment outcome.
      The study of rare inherited DNA repair disorders, such as Fanconi anemia, has
      yielded new insights to drug sensitivity and treatment of sporadic cancers, such
      as breast or ovarian epithelial tumors, in the general population. The Fanconi
      anemia pathway is an example of how DNA repair pathways can be deregulated in
      cancer cells and how biomarkers of the integrity of these pathways could be
      useful as a guide to cancer management and may be used in the development of
      novel therapeutic agents.

PMID- 16896010
TI  - Ki-67 correlates with in vivo bromodeoxyuridine labeling index in operable breast
      cancer.

PMID- 16896011
TI  - Prospective study of wide excision alone for ductal carcinoma in situ of the
      breast.

PMID- 16896012
TI  - Imatinib and pregnancy.

PMID- 16896013
TI  - A RecA-mediated exon profiling method.
AB  - We have developed a RecA-mediated simple, rapid and scalable method for
      identifying novel alternatively spliced full-length cDNA candidates. This method
      is based on the principle that RecA proteins allow to carry radioisotope-labeled
      probe DNAs to their homologous sequences, resulting in forming triplexes. The
      resulting complex is easily detected by mobility difference on electrophoresis.
      We applied this exon profiling method to four selected mouse genes as a
      feasibility study. To design probes for detection, the information on known
      exonic regions was extracted from public database, RefSeq. Concerning the
      potentially transcribed novel exonic regions, RNA mapping experiment using
      Affymetrix tiling array was performed. As a result, we were able to identify
      alternative splice variants of Thioredoxin domain containing 5, Interleukin1beta,
      Interleukin 1 family 6 and glutamine-rich hypothetical protein. In addition, full
      length sequencing demonstrated that our method could profile exon structures with
      >90% accuracy. This reliable method can allow us to screen novel splice variants
      from a huge number of cDNA clone set effectively.

PMID- 16896015
TI  - PharmD Accreditation Standards 2007: much is implied, little is required.

PMID- 16896014
TI  - Characterization of RNA sequence determinants and antideterminants of processing
      reactivity for a minimal substrate of Escherichia coli ribonuclease III.
AB  - Members of the ribonuclease III family are the primary agents of double-stranded
      (ds) RNA processing in prokaryotic and eukaryotic cells. Bacterial RNase III
      orthologs cleave their substrates in a highly site-specific manner, which is
      necessary for optimal RNA function or proper decay rates. The processing
      reactivities of Escherichia coli RNase III substrates are determined in part by
      the sequence content of two discrete double-helical elements, termed the distal
      box (db) and proximal box (pb). A minimal substrate of E.coli RNase III, muR1.1
      RNA, was characterized and used to define the db and pb sequence requirements for
      reactivity and their involvement in cleavage site selection. The reactivities of
      muR1.1 RNA sequence variants were examined in assays of cleavage and binding in
      vitro. The ability of all examined substitutions in the db to inhibit cleavage by
      weakening RNase III binding indicates that the db is a positive determinant of
      RNase III recognition, with the canonical UA/UG sequence conferring optimal
      recognition. A similar analysis showed that the pb also functions as a positive
      recognition determinant. It also was shown that the ability of the GC or CG bp
      substitution at a specific position in the pb to inhibit RNase III binding is due
      to the purine 2-amino group, which acts as a minor groove recognition
      antideterminant. In contrast, a GC or CG bp at the pb position adjacent to the
      scissile bond can suppress cleavage without inhibiting binding, and thus act as a
      catalytic antideterminant. It is shown that a single pb+db 'set' is sufficient to
      specify a cleavage site, supporting the primary function of the two boxes as
      positive recognition determinants. The base pair sequence control of reactivity
      is discussed within the context of new structural information on a post-catalytic
      complex of a bacterial RNase III bound to the cleaved minimal substrate.

PMID- 16896016
TI  - Prevalence and treatment of metabolic syndrome in adolescents with type 2
      diabetes.
AB  - BACKGROUND: The incidence of obesity and type 2 diabetes among adolescents has
      risen dramatically in recent years, and it is likely that many of these
      adolescents also have metabolic syndrome. OBJECTIVE: To investigate the
      prevalence of metabolic syndrome in the patient population enrolled in a
      children's hospital type 2 diabetes clinic and to describe baseline pharmacologic
      treatment and adherence patterns. METHODS: In this retrospective cohort study,
      the medical charts of 52 adolescents were reviewed. A data collection instrument
      was used to collect demographic data, laboratory values, medication lists, and
      documented adherence patterns from the patient's initial clinic visit. Data
      collected were used to identify patients with metabolic syndrome. Data were
      entered into a database and analyzed using SPSS 13.0. RESULTS: Data were
      collected for 52 patients; of these, 40 (76.9%) had characteristics of metabolic
      syndrome meeting 3 or more of the 5 criteria, although only 8 (15.4%) were
      diagnosed with the metabolic syndrome. Among patients with characteristics of
      metabolic syndrome, 92.5% were taking a glucose-lowering drug, with 85% of those
      receiving metformin. Sixteen (40%) patients were receiving a blood pressure
      lowering medication at baseline, and 4 (10%) were taking a lipid-lowering agent.
      Forty-three percent of these patients reported nonadherence to their prescribed
      drugs. CONCLUSIONS: Given these treatment patterns, pharmacologic management of
      metabolic syndrome in adolescents with type 2 diabetes may be suboptimal and may
      impact cardiovascular outcomes. It is important for clinicians to be aware of the
      incidence of type 2 diabetes and metabolic syndrome in adolescents so that
      treatment with lifestyle modifications and pharmacologic therapy may be
      implemented earlier.

PMID- 16896017
TI  - Lichenoid eruption associated with the use of nebivolol.
AB  - OBJECTIVE: To report a case of lichenoid drug eruption (LDE) after starting
      antihypertensive treatment with nebivolol, a cardioselective beta-blocker. CASE
      SUMMARY: Five weeks after starting treatment with nebivolol, a 62-year-old woman
      presented with erythematous papules on both extremities and skin lesions
      spreading over the back. She was not being treated with any other drugs. Because
      the administration of levocetirizine, topical methylprednisolone, and systemic
      prednisone was unsuccessful, the treatment was stopped and the lesions were
      biopsied. The histopathological features of the lesions were consistent with LDE.
      After withdrawal of nebivolol and subsequent readministration of topical
      methylprednisolone and systemic prednisone, the skin lesions resolved within 12
      days. Assessment of the causality revealed a probable relationship between
      nebivolol and the lichenoid eruptions. DISCUSSION: Although beta-blockers can be
      associated with LDE, as of July 7, 2006, this has not been previously reported
      with nebivolol. T cells invading the dermis are considered to be responsible for
      epidermal destruction associated with LDE, as has been described for lichenoid
      forms of chronic graft versus host disease and idiopathic lichen ruber planus.
      CONCLUSIONS: Nebivolol can cause LDE, as has been reported with other beta
      blockers. The underlying mechanism appears to be T cell-mediated. Cross
      reactivity with other beta-blockers cannot be excluded; therefore, the risk of
      recurrent LDE should be weighed carefully against the clinical benefit before
      switching to another beta-blocker.

PMID- 16896018
TI  - Doxycycline for community-associated methicillin-resistant Staphylococcus aureus
      skin and soft-tissue infections.

PMID- 16896019
TI  - Drug therapy recommendations from the 2005 ACC/AHA guidelines for treatment of
      chronic heart failure.
AB  - OBJECTIVE: To review and discuss key aspects of the drug therapy recommendations
      in the American College of Cardiology (ACC)/American Heart Association (AHA) 2005
      Guideline Update for the Diagnosis and Management of Chronic Heart Failure (HF)
      in the Adult. DATA SOURCES: Data were obtained from the ACC/AHA 2005 Guideline
      Update for Chronic HF. English-language clinical trials, observational studies,
      and pertinent review articles evaluating the pharmacotherapy of chronic HF were
      identified, based on MEDLINE searches through January 2006. STUDY SELECTION:
      Articles presenting information that impacts the evidence base for
      recommendations regarding the use of various drug therapies in patients with
      chronic HF were evaluated. DATA SYNTHESIS: The ACC/AHA 2005 Guideline Update for
      HF provides revised, evidence-based recommendations for the treatment of chronic
      HF. The new guidelines are based on a staging system that recognizes both the
      development and progression of HF. Recommendations are provided for 2 stages of
      patients (A and B) who do not yet have clinical HF but are clearly at risk and 2
      stages (C and D) that include patients with symptomatic HF. The guidelines
      continue to emphasize the important role of neurohormonal blockade with
      angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, beta
      adrenergic blockers, and aldosterone antagonists. Based on recent trials, updated
      recommendations address the roles of combination therapy and the selective
      addition of hydralazine and isosorbide dinitrate. Along with specific drug
      recommendations, information on the practical use of various drugs is provided.
      Although the guidelines primarily focus on HF due to systolic dysfunction,
      general recommendations are also provided for patients with preserved systolic
      function. CONCLUSIONS: The ACC/AHA 2005 Guideline Update provides evidence-based
      recommendations for healthcare professionals involved in the care of adults with
      chronic HF. Recent clinical trial findings have further clarified the evolving
      role of neurohormonal-blocking drugs in the prevention and treatment of HF.

PMID- 16896020
TI  - Hypotension following treatment with aerosolized colistin in a patient with
      multidrug-resistant Pseudomonas aeruginosa.
AB  - OBJECTIVE: To report a case of a man who developed temporary hypotension after
      aerosolized colistin administration. CASE SUMMARY: A 62-year-old Arab male was
      admitted to the intensive care unit for respiratory failure and septic shock.
      Simultaneous therapy using intravenous and aerosolized colistin was initiated for
      the management of multidrug-resistant Pseudomonas aeruginosa. A significant but
      transient drop in blood pressure occurred when aerosolized colistin was
      introduced. However, when it was stopped, but intravenous administration was
      continued, no hypotension was observed. Moreover, the combined use of aerosolized
      amikacin with intravenous colistin did not significantly affect blood pressure.
      DISCUSSION: It is widely accepted that aerosolization allows safe administration
      of colistin in the absence of significant systemic adverse effects. However, in
      our patient, hypotension was observed with aerosolized colistin, but not with the
      systemic formulation. The lack of adverse effects with administration of
      aerosolized amikacin in this patient demonstrates the safety of the
      aerosolization technique. Use of the Naranjo scale indicated a probable
      relationship between hypotension and aerosolized colistin administration.
      CONCLUSIONS: This case suggests that hypotension may be induced with
      administration of aerosolized colistin. Although this effect is rare, clinicians
      should be aware that hypotension may develop in critically ill patients following
      aerosolized colistin treatment.

PMID- 16896021
TI  - Pancytopenia with levofloxacin therapy for pelvic inflammatory disease in an
      otherwise healthy young patient.

PMID- 16896022
TI  - Dose-dependent urinary retention following olanzapine administration.

PMID- 16896024
TI  - Clinical psychopharmacology: advances and challenges from 1965 to 2006.

PMID- 16896025
TI  - What interventions should pharmacists employ to impact health practitioners'
      prescribing practices?
AB  - OBJECTIVE: To determine which interventions are effective in influencing health
      practitioners' prescribing practices and explore differences in intervention
      complexity, setting, sustainability, cost effectiveness, and impact on patient
      outcomes. METHODS: A systematic search for English-language systematic reviews
      was performed in MEDLINE, Cumulative Index of Nursing and Allied Health
      Literature, EMBASE, and the Cochrane Library from the date of inception to July
      2005 using search terms in accordance with Cochrane recommendations. Included
      reviews were required to clearly report a search strategy, inclusion/exclusion
      criteria, literature assessment criteria, and methods for synthesizing or
      summarizing information and references. Two reviewers independently identified
      studies for inclusion, assessed study quality, and extracted relevant
      information. Interventions were classified as consistently effective,
      inconsistently effective, and effectiveness uncertain. RESULTS: Thirty-four of
      4585 titles reviewed met the inclusion criteria. Quality scores ranged from 70%
      to 100%. Consistently effective interventions included reminders (manual and
      computerized), audit and feedback, educational outreach visits, organizational
      strategies, and patient-mediated interventions. Inconsistently effective
      interventions included computer decision support systems and educational
      meetings. Multi-faceted interventions were consistently shown to be more
      efficacious than single interventions. Limited data precluded exploration of the
      effects of interventions in different settings, sustainability of effect, cost
      effectiveness, and patient clinical outcomes. CONCLUSIONS: Interventions that are
      most effective for impacting prescribing practice include audit and feedback,
      reminders, educational outreach visits, and patient-mediated interventions. To
      maximize impact, pharmacists' efforts to positively impact prescribing practices
      should focus on these intervention types rather than relying primarily on passive
      didactics or dissemination of guidelines.

PMID- 16896026
TI  - Hyponatremia associated with selective serotonin-reuptake inhibitors in older
      adults.
AB  - OBJECTIVE: To review the incidence, risk factors, mechanism, times of onset and
      resolution, and treatment of hyponatremia associated with selective serotonin
      reuptake inhibitors (SSRIs). DATA SOURCES: An English-language literature search
      was conducted using MEDLINE (1966-December 2005) using the search terms selective
      serotonin-reuptake inhibitor, hyponatremia, syndrome of inappropriate secretion
      of antidiuretic hormone, citalopram, escitalopram, fluoxetine, fluvoxamine,
      paroxetine, and sertraline. Additional references were identified by reviewing
      bibliographies of articles retrieved. STUDY SELECTION AND DATA EXTRACTION:
      Relevant data were extracted from published reports, letters, and studies of
      humans with hyponatremia and/or syndrome of inappropriate secretion of
      antidiuretic hormone (SIADH) secondary to SSRIs. All articles identified from
      data sources were reviewed for relevant information. Applicable information was
      included in this review. DATA SYNTHESIS: Numerous case reports, observational
      studies, and case-controlled studies, as well as one prospective clinical trial,
      have reported hyponatremia associated with SSRI use, with the incidence varying
      from 0.5% to 32%. Risk factors for the development of hyponatremia with SSRIs
      include older age, female gender, concomitant use of diuretics, low body weight,
      and lower baseline serum sodium concentration. In published reports, hyponatremia
      developed within the first few weeks of treatment and resolved within 2 weeks
      after therapy was discontinued. The mechanism by which SSRIs cause hyponatremia
      is thought to be secondary to development of SIADH. Treatment of isovolemia
      hypotonic hyponatremia associated with SSRI use includes water restriction and
      mild diuresis with a loop diuretic. More severe cases may be treated with higher
      doses of loop diuretics and hypertonic saline. There have been few reports of
      rechallenge with the same or another SSRI or substitution of another agent from a
      different therapeutic class. In some, but not all, cases hyponatremia recurred.
      CONCLUSIONS: Practitioners should be on the alert for this potentially life
      threatening adverse event, especially in older adults with other risk factors for
      developing hyponatremia.

PMID- 16896027
TI  - An Interlocker concept of carcinogenesis.
AB  - A critical feature in the sequence of events occurring during carcinogenesis is
      the development of irreversibility. The term "Interlocker" is used here to denote
      a mechanism by which irreversibility is brought about. The presentation focuses
      on conceptualizations of such processes. Two will be described below.

PMID- 16896028
TI  - Vitamin D, calcium, and breast cancer risk: a review.
AB  - Vitamin D and calcium are metabolically interrelated and highly correlated
      dietary factors. Experimental studies have shown their anticarcinogenic effects
      due to their participation in regulating cell proliferation, differentiation, and
      apoptosis in normal and malignant breast cells. Given the emerging interest in
      their potential roles in the etiology of breast cancer, we review the current
      epidemiologic literature on dietary and/or supplemental intakes of vitamin D,
      endogenous circulating levels of vitamin D, and dietary and/or supplemental
      intakes of calcium in relation to breast cancer risk. To place these studies in
      context, we also provide a brief review of other supporting epidemiologic
      evidence. Despite inconsistent results from the epidemiologic studies, several
      lines of evidence suggest that vitamin D and calcium may be involved in the
      development of breast cancer. Specifically, (a) there is some epidemiologic
      evidence for inverse associations between vitamin D and calcium intakes and
      breast cancer; (b) serum, plasma, and/or blood levels of vitamin D metabolites
      have been inversely associated with breast cancer risk in some studies; (c) high
      sunlight exposure, presumably reflecting vitamin D synthesis in the skin, has
      been associated with a reduced risk of breast cancer; (d) vitamin D and calcium
      intakes have been inversely related to breast density, an intermediate end point
      for breast cancer; (e) calcium has been associated with a reduced risk of benign
      proliferative epithelial disorders of the breast, putative precursors of breast
      cancer; and (f) certain polymorphisms of the vitamin D receptor might modify
      breast cancer susceptibility. To further confirm the potential protective effects
      of calcium and vitamin D on breast cancer, well-designed cohort studies and
      clinical trials are warranted.

PMID- 16896029
TI  - A follow-up study of physical activity and incidence of colorectal polyps in
      African-American women.
AB  - BACKGROUND: Physical activity is associated with a reduced risk of colon cancer,
      but the effect of activity on colorectal adenomas, which are precursors to colon
      cancer, is uncertain. The influence of physical activity on colorectal adenomas
      among African-American women is of particular interest because African-American
      women have an increased risk of colon cancer relative to other U.S. women.
      METHODS: We prospectively assessed the relation of physical activity to the
      incidence of colorectal polyps among African-American women. We followed 45,400
      women in the Black Women's Health Study from 1997 to 2003. Data were obtained by
      biennial mailed questionnaires. During 287,029 person-years of follow-up, 1,390
      women reported having been diagnosed with colorectal polyps. A review of medical
      records of 58 women who reported colorectal polyps indicated that 59% had
      adenomas and 41% had hyperplastic polyps. We converted hours per week of vigorous
      exercise and hours per week of walking to metabolic equivalent (MET)-hours. We
      estimated incidence rate ratios with Cox proportional hazard models, controlling
      for age, body mass index, smoking, family history of colorectal cancer, and
      education. RESULTS: For total MET-hours/wk spent in walking and vigorous
      exercise, the incidence rate ratio decreased from 0.94 for <5 MET-hours/wk to
      0.72 for >or=40 MET-hours/wk (P(trend) = 0.01). The inverse association was
      apparent among most subgroups examined, including women who may be at higher risk
      of colorectal adenomas because of being obese. CONCLUSIONS: Increased physical
      activity is associated with a reduced incidence of colorectal polyps among
      African-American women.

PMID- 16896032
TI  - Diabetes mellitus and pancreatic cancer in a population-based case-control study
      in the San Francisco Bay Area, California.
AB  - BACKGROUND: Diabetes has been postulated to be both a risk factor and a
      consequence of pancreatic cancer, but the degree of risk and associated clinical
      factors remain unclear. METHODS: We conducted a population-based case-control
      study of pancreatic cancer in the San Francisco Bay Area between 1995 and 1999.
      Rapid case ascertainment through the Surveillance, Epidemiology and End Results
      registry for cases and random selection from the general population for controls
      were employed to identify study participants with no proxy interviews. RESULTS:
      Five hundred thirty-two cases and 1,701 controls were interviewed. Participants
      with pancreatic cancer were more likely to report a history of diabetes (13%)
      than were controls [9%; odds ratio (OR), 1.5; 95% confidence interval (95% CI),
      1.1-2.1]. Compared with diabetics in the control group, diabetics in the case
      group had a shorter duration of diabetes (P = 0.0003) and a larger proportion of
      insulin users (P = 0.002). Risk for pancreatic cancer varied with duration of
      diabetes (OR, 2.4; 95% CI, 1.4-4.0 for 1-4 years; OR, 2.0; 95% CI, 1.2-3.4 for 5
      9 years; and OR, 0.86; 95% CI, 0.52-1.4 for >or=10 years diabetes duration;
      P(trend) = 0.004). Among diabetics, use of oral diabetes medication or insulin
      for >or=5 years was not associated with pancreatic cancer, but insulin use of <5
      years was associated with a 6.8-fold risk for pancreatic cancer (95% CI, 3.7-12).
      CONCLUSION: Recent-onset diabetes may be a complication or an early marker of
      pancreatic cancer. Diabetes of short duration with insulin use conferred a
      substantially elevated risk for pancreatic cancer and may reflect insulin
      resistance that is elicited by pancreatic cancer.

PMID- 16896031
TI  - Chromosomal instability in Barrett's esophagus is related to telomere shortening.
AB  - Barrett's esophagus is a useful model for the study of carcinogenesis, as the
      metaplastic columnar epithelium that replaces squamous esophageal epithelium is
      at elevated risk for development of adenocarcinoma. We examined telomere length
      and chromosomal instability (CIN) in Barrett's esophagus biopsies using
      fluorescence in situ hybridization. To study CIN, we selected centromere and
      locus-specific arm probes to chromosomes 17/17p (p53), 11/11q (cyclin D1), and
      9/9p (p16 INK4A), loci reported to be involved in early stages of Barrett's
      esophagus neoplasia. Telomere shortening was observed in Barrett's esophagus
      epithelium at all histologic grades, whereas CIN was highest in biopsies with
      dysplastic changes; there was, however, considerable heterogeneity between
      patients in each variable. Alterations on chromosome 17 were strongly correlated
      with telomere length (r = 0.55; P < 0.0001) and loss of the 17p arm signal was
      the most common event. CIN on chromosome 11 was also associated with telomere
      shortening (r =0.3; P = 0.05), although 11q arm gains were most common. On
      chromosome 9p, arm losses were the most common finding, but chromosome 9 CIN was
      not strongly correlated with telomere length. We conclude that CIN is related to
      telomere shortening in Barrett's esophagus but varies by chromosome. Whether
      instability is manifested as loss or gain seems to be influenced by the
      chromosomal loci involved. Because telomere shortening and CIN are early events
      in Barrett's esophagus neoplastic progression and are highly variable among
      patients, it will be important to determine whether they identify a subset of
      patients that is at risk for more rapid neoplastic evolution.

PMID- 16896033
TI  - Tobacco use in adult long-term survivors of retinoblastoma.
AB  - A significant risk of lung cancer was identified among hereditary, but not
      nonhereditary, retinoblastoma (Rb) patients. Tobacco use was investigated to
      determine whether differences in smoking prevalence might explain the lung cancer
      excess and to characterize smoking patterns in adult survivors of Rb. Subjects
      were 441 hereditary and 395 nonhereditary 1-year survivors of Rb, age >or=18
      years, who responded to a telephone survey about current health behavior,
      including tobacco use. Response rates were 76% for hereditary and 73% for
      nonhereditary survivors. We compared patterns and predictors of current tobacco
      use among hereditary and nonhereditary survivors with other childhood cancer
      survivor studies and the U.S. population. Hereditary Rb survivors currently smoke
      cigarettes significantly less frequently than nonhereditary survivors (16. 8%
      versus 24.3%), although among current smokers, age at smoking initiation (17
      years old) and average cigarettes (1.5 packs) smoked daily are similar.
      Predictors of current and ever cigarette smoking include nonhereditary Rb, older
      age, being female, less education, and use of other tobacco products. Rb
      survivors smoke cigarettes significantly less than the U.S. population (rate
      ratio, 0.63; 95% confidence interval, 0.5-0.8 for males; rate ratio, 0.75; 95%
      confidence interval, 0.6-0.9 for females), but Rb survivors have comparable
      smoking rates with other childhood cancer survivors. Smoking did not account for
      the increased risk of lung cancer among hereditary Rb patients, and this may
      point to an enhanced sensitivity to the carcinogenic effects of tobacco. Adult
      survivors of Rb should be encouraged to stop smoking.

PMID- 16896034
TI  - Estrogen and alpha-fetoprotein levels in maternal and umbilical cord blood
      samples in relation to birth weight.
AB  - Birth weight has been associated with a subsequent risk of breast cancer. The
      present study examined associations between birth weight and pregnancy estrogens
      and alpha-fetoprotein (AFP). The concentrations of estradiol, estriol, and AFP
      were measured in maternal and umbilical cord blood samples from 194 women during
      pregnancy and at birth. Birth weight was significantly positively correlated with
      maternal serum estradiol and estriol levels in the 29th week (estradiol: r =
      0.16, P = 0.03; estriol: r = 0.29, P = 0.001) and at delivery (estradiol: r =
      0.20, P = 0.01; estriol: r = 0.41, P < 0.0001) after controlling for covariates.
      The umbilical cord estriol level was moderately but significantly correlated with
      birth weight (r = 0.15, P = 0.049). There was no significant association between
      umbilical cord serum estradiol and birth weight. There was no significant
      association between birth weight and maternal serum AFP in any gestational week.
      Umbilical cord AFP was significantly inversely correlated with birth weight (r = 
      0.16, P = 0.04). Umbilical cord AFP was unrelated to cord levels of estradiol and
      estriol. The data suggested a greater exposure to estriol and a lower exposure to
      AFP among high birth weight babies.

PMID- 16896030
TI  - Associations of Ki-ras proto-oncogene mutation and p53 gene overexpression in
      sporadic colorectal adenomas with demographic and clinicopathologic
      characteristics.
AB  - In colorectal tumorigenesis, Ki-ras proto-oncogene mutation often occurs early in
      the adenoma-adenocarcinoma sequence, whereas mutation of the p53 gene is
      associated with late progression to carcinoma. We evaluated the relationship of
      demographic and clinicopathologic characteristics to Ki-ras mutation and p53 gene
      product overexpression in 1,093 baseline sporadic colorectal adenomas from 926
      individuals enrolled in a phase III recurrence prevention trial. Ki-ras mutation
      was found in 14.7% of individuals and p53 overexpression was found in 7.0% of
      those tested. Multivariate analysis found older age, rectal location, and villous
      histology to be independently associated with Ki-ras mutation. Individuals with
      an advanced adenoma (>or=1 cm or high-grade dysplasia or villous histology) had a
      4-fold higher likelihood of Ki-ras mutation [odds ratios (OR), 3.96; 95%
      confidence intervals (CI), 2.54-6.18]. Ki-ras mutations in codon 12 and of the G
      to-A transition type were more frequent in older individuals, whereas G-to-T
      transversion was more frequent in rectal adenomas than in the colon. Multivariate
      analysis showed that previous history of a polyp (P = 0.03) was inversely
      associated with p53 overexpression. Large adenoma size (>or=1 cm), high-grade
      dysplasia, and villous histology were independently associated with p53
      overexpression, with the strongest association for advanced adenomas (OR, 7.20;
      95% CI, 3.01-17.22). Individuals with a Ki-ras mutated adenoma were more likely
      to overexpress p53 (OR, 2.46; 95% CI, 1.36-4.46), and 94.8% of adenomas with both
      alterations were classified as advanced (P <or= 0.0001). Our large cross
      sectional study supports the role of both Ki-ras and p53 in the progression of
      adenomas and shows that their molecular pathogenesis differs by anatomic
      location, age, and mucosal predisposition as evidenced by previous history of a
      polyp.

PMID- 16896035
TI  - Deletion polymorphism of UDP-glucuronosyltransferase 2B17 and risk of prostate
      cancer in African American and Caucasian men.
AB  - PURPOSE: UDP-glucuronosyltransferases (UGT) are a family of enzymes that
      glucuronidate many endogenous chemicals, including androgens. This makes them
      more hydrophilic, alters biological activity, and facilitates their excretion. A
      deletion polymorphism in the UGT2B17 gene was recently described that was
      associated with a reduced rate of glucuronidation in vivo. The purpose of this
      study was to determine if the deletion polymorphism is associated with
      susceptibility to prostate cancer. MATERIALS AND METHODS: UGT2B17 expression was
      determined by reverse transcription-PCR of pathologically normal prostate tissues
      (n = 5). In a case-control study with 420 patients with incident primary prostate
      cancer (127 African Americans and 293 Caucasians) and 487 controls (120 African
      Americans and 367 Caucasians), the frequency of UGT2B17 deletion polymorphism in
      genomic DNA was compared between cases and controls with PCR analysis. RESULTS:
      UGT2B17 mRNA was detected only in individuals with at least one UGT2B17 allele.
      The frequency of the null genotype was present in 0.11 and 0.12 of Caucasian and
      African American controls, respectively. When all subjects were considered, a
      significant association was found between the UGT2B17 deletion polymorphism and
      prostate cancer risk [odds ratio (OR), 1.7; 95% confidence interval (95% CI), 1.2
      2.6]. There was an increase in prostate cancer risk among individuals with
      UGT2B17 deletion polymorphism in Caucasians (OR, 1.9; 95% CI, 1.2-3.0) but not in
      African Americans (OR, 1.3; 95% CI, 0.6-2.7). CONCLUSIONS: These results suggest
      that the UGT2B17 enzyme may play a role in the metabolism of androgens in
      prostate tissue and that the UGT2B17 deletion polymorphism is associated with
      prostate cancer risk.

PMID- 16896036
TI  - Design and progress of a trial of selenium to prevent prostate cancer among men
      with high-grade prostatic intraepithelial neoplasia.
AB  - High-grade prostatic intraepithelial neoplasia (HGPIN) is generally regarded as a
      premalignant lesion that progresses toward prostate cancer. In light of the
      significant sequelae of prostate cancer treatment, prevention is desirable, and
      men with HGPIN would be suitable, high-risk subjects. There is in vitro, in vivo,
      epidemiologic, and human experimental evidence that selenium supplementation may
      protect against prostate cancer. This article introduces the rationale for, and
      progress to date, of a double-blind, randomized, placebo-controlled trial of
      selenium supplementation (200 mug/d in the form of selenomethionine), to prevent
      the development of prostate cancer among men with HGPIN. The trial, Southwest
      Oncology Group Protocol 9917, funded by a National Cancer Institute program
      supporting pivotal prevention trials has registered 537 patients and has
      randomized >380 to date. Subject accrual is expected to be completed by the fall
      of 2006, with trial completion in 2009.

PMID- 16896037
TI  - The cost of prostate cancer chemoprevention: a decision analysis model.
AB  - BACKGROUND: The Prostate Cancer Prevention Trial found reduced prostate cancer
      prevalence for men treated with finasteride. The public health cost of wide-scale
      chemoprevention is unclear. We developed a model to help clarify the cost
      effectiveness of public use of prostate cancer-preventive agents. METHODS: A
      Markov decision analysis model was designed to determine the lifetime prostate
      health-related costs, beginning at the age of 50 years, for men treated with
      finasteride compared with placebo. Model assumptions were based on data from the
      Prostate Cancer Prevention Trial, a literature review of survival and progression
      rates for patients treated with radical prostatectomy, and costs associated with
      prostate cancer disease states. RESULTS: Chemoprevention with finasteride
      resulted in a gain of 8.7 [corrected] life years per 1,000 men at a cost of
      $1.107 million [corrected] per life year saved (LYS). However, if finasteride is
      assumed to not increase the incidence of high-grade tumors, it renders a gain of
      16.9 [corrected] life years per 1,000 men at a cost of $578,400 [corrected] per
      LYS; finasteride must cost $160 per year [corrected] to reach $100,000
      [corrected] per LYS. When applied to a population at higher risk (lifetime
      prevalence >or=40%) [corrected]for developing prostate cancer, the cost of
      finasteride must be reduced from its current cost ($62/month) to <$15/month
      [corrected]for the cost effectiveness to fall below $50,000 [corrected] per LYS.
      CONCLUSIONS: Given the natural history of treated prostate cancer, implementation
      of chemoprevention would require an inexpensive medication with substantial
      cancer risk reduction to be cost effective. Targeting populations at higher risk
      for developing prostate cancer, however, allows for considerable flexibility in
      the medication cost to make prostate cancer chemoprevention a more attainable
      goal.

PMID- 16896038
TI  - Combined analysis of r-1,t-2,3,c-4-tetrahydroxy-1,2,3,4-tetrahydrophenanthrene
      and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol in smokers' plasma.
AB  - Polycyclic aromatic hydrocarbons (PAH) and tobacco-specific nitrosamines, such as
      4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), are widely accepted to be
      two important types of lung carcinogens in cigarette smoke. In this study, we
      have developed a method to estimate individual uptake of these compounds by
      quantifying r-1,t-2,3,c-4-tetrahydroxy-1,2,3,4-tetrahydrophenanthrene (PheT) and
      4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) in 1 mL of smokers' plasma.
      PheT and NNAL are biomarkers of PAH and NNK uptake, respectively. [D10]PheT and
      [pyridine-D4]NNAL were added to plasma as internal standards. The plasma was
      treated with beta-glucuronidase to release any conjugated PheT and NNAL. The
      analytes were enriched by solid-phase extraction on a mixed mode cation exchange
      cartridge and the PheT fraction was further purified by high-performance liquid
      chromatography. The appropriate fractions were analyzed by gas chromatography
      negative ion chemical ionization-mass spectrometry for PheT and liquid
      chromatography-electrospray ionization-mass spectrometry for NNAL. The method was
      sensitive (limits of quantitation: PheT, 13 fmol/mL; NNAL, 3 fmol/mL), accurate,
      and precise. Levels of PheT and NNAL in plasma from 16 smokers averaged 95 +/- 71
      and 36 +/- 21 fmol/mL, respectively, which are approximately 1% to 2% of the
      amounts found in urine. This method should be useful in molecular epidemiology
      studies of carcinogen uptake and lung cancer in smokers.

PMID- 16896039
TI  - Cigarette yields and human exposure: a comparison of alternative testing
      regimens.
AB  - OBJECTIVE: There is general agreement that the testing protocol for measuring
      cigarette smoke constituents-the International Organization for Standardization
      regimen-is an inappropriate mechanism for evaluating human exposure. Alternative
      smoking regimens have been introduced in Canada and Massachusetts; however, these
      regimens have not been evaluated against human smoking behavior and biomeasures
      of exposure. The objective of this study was to compare measures of smoke volume
      and nicotine uptake among human smokers against the puffing variables and
      nicotine yields generated by five different machine smoking regimens: (a)
      International Organization for Standardization, (b) Massachusetts, (c) Canadian,
      (d) a Compensatory regimen, and (e) a Human Mimic regimen. METHODS: Measures of
      smoke volume and puffing behavior were recorded for 51 smokers who used a
      portable smoking topography device for three 1-week trials. Measures of salivary
      cotinine were taken at the completion of each week. The cigarette brands smoked
      by participants were then machine-smoked under five testing regimens, including a
      human mimic condition where brands were machine smoked using the puffing behavior
      recorded from human smokers. The total volume of smoke collected from each
      cigarette and the nicotine, tar, and carbon monoxide yields were recorded.
      RESULTS: None of the four machine smoking regimens adequately reflected Human
      Mimic Yields of tar, nicotine, and carbon monoxide. In addition, none of the four
      smoking regimens generated nicotine yields that were associated with actual
      nicotine uptake in humans. CONCLUSIONS: None of the existing smoking regimens
      adequately represents human smoking behavior nor do they generate yields
      associated with human measures of nicotine uptake.

PMID- 16896040
TI  - Associations among mammographic density, circulating sex hormones, and
      polymorphisms in sex hormone metabolism genes in postmenopausal women.
AB  - Mammographic density and serum sex hormone levels are important risk factors for
      breast cancer, but their associations with one another are unclear. We studied
      these phenotypes, together with single nucleotide polymorphisms (SNP) in genes
      related to sex hormone metabolism, in a cross-sectional study of 1,413
      postmenopausal women from the European Prospective Investigation into Cancer and
      Nutrition-Norfolk. All women were >1 year postmenopausal and had not taken
      hormone replacement therapy for >3 months before sampling. Serum levels of 7 sex
      hormones [estradiol, testosterone, sex hormone-binding globulin (SHBG),
      androstenedione, 17-OH-progesterone, estrone, and estrone sulfate] and 15 SNPs in
      the CYP17, CYP19, EDH17B2, SHBG, COMT, and CYP1B1 genes were studied. Mammograms
      nearest in time to the blood sampling were identified through the national breast
      screening program and visually assessed by three radiologists using the Boyd six
      category and Wolfe four-category scales. We found a weak positive association
      between mammographic density and SHBG levels (P = 0.09) but no association with
      any other hormones. None of the SNPs, including those shown previously to be
      associated with estradiol or SHBG, showed significant associations with density.
      We conclude that mammographic density is largely independent of postmenopausal
      steroid hormone levels, indicating that these risk factors have, to a large
      extent, an independent etiology and suggesting that they may be independent
      predictors of breast cancer risk.

PMID- 16896041
TI  - Prenatal diethylstilbestrol exposure and risk of breast cancer.
AB  - It has been hypothesized that breast cancer risk is influenced by prenatal
      hormone levels. Diethylstilbestrol (DES), a synthetic estrogen, was widely used
      by pregnant women in the 1950s and 1960s. Women who took the drug have an
      increased risk of breast cancer, but whether risk is also increased in the
      daughters who were exposed in utero is less clear. We assessed the relation of
      prenatal DES exposure to risk of breast cancer in a cohort of DES-exposed and
      unexposed women followed since the 1970s by mailed questionnaires. Eighty percent
      of both exposed and unexposed women completed the most recent questionnaire. Self
      reports of breast cancer were confirmed by pathology reports. Cox proportional
      hazards regression was used to compute incidence rate ratios (IRR) for prenatal
      DES exposure relative to no exposure. During follow-up, 102 incident cases of
      invasive breast cancer occurred, with 76 among DES-exposed women (98,591 person
      years) and 26 among unexposed women (35,046 person-years). The overall age
      adjusted IRR was 1.40 [95% confidence interval (95% CI), 0.89-2.22]. For breast
      cancer occurring at ages >or=40 years, the IRR was 1.91 (95% CI, 1.09-3.33) and
      for cancers occurring at ages >or=50 years, it was 3.00 (95% CI, 1.01-8.98).
      Control for calendar year, parity, age at first birth, and other factors did not
      alter the results. These results, from the first prospective study on the
      subject, suggest that women with prenatal exposure to DES have an increased risk
      of breast cancer after age 40 years. The findings support the hypothesis that
      prenatal hormone levels influence breast cancer risk.

PMID- 16896042
TI  - Differences in cancer incidence among Indians in Alaska and New Mexico and U.S.
      Whites, 1993-2002.
AB  - Cancer incidence for American Indians and Alaska Natives is typically reported as
      a single rate for all U.S. indigenous populations combined. Previously reported
      combined rates suggest that American Indians and Alaska Natives have lower cancer
      incidence rates compared with the U.S. population. Alaska Native people comprise
      three major ethnic groups: Eskimo, Indian, and Aleut people. We examined cancer
      incidence from only Alaska Indians and compared incidence rates with an American
      Indian population living in New Mexico. These data indicate striking differences
      in cancer patterns between two American Indian populations. Cancer data for the
      years 1993 to 2002 for American Indians of New Mexico and U.S. Whites are from
      the National Cancer Institute Surveillance, Epidemiology, and End Results Program
      Public-use data set. Data for Alaska Indians are from the Alaska Native Tumor
      Registry, which is also a Surveillance Epidemiology and End Results Program
      participant. Overall, cancer incidence rates for all sites combined in New Mexico
      Indian men and women were lower than U.S. White rates, whereas Alaska Indian men
      and women exceeded U.S. rates. In comparing Alaska and New Mexico Indians, we
      observed a 2.5-fold higher incidence of cancer among Alaska Indians. The largest
      differences between the two Indian populations were noted primarily in cancers
      associated with tobacco use, including cancers of the oral cavity/pharynx,
      esophagus (only in men), colon and rectum, pancreas, larynx (men), lung,
      prostate, and urinary bladder (men). Lung cancer rates in Alaska Indian men and
      women were 7 and 10 times those of New Mexico Indian men and women.

PMID- 16896043
TI  - The prevalence of CDKN2A germ-line mutations and relative risk for cutaneous
      malignant melanoma: an international population-based study.
AB  - Germ-line mutations of CDKN2A have been identified as strong risk factors for
      melanoma in studies of multiple-case families. However, an assessment of their
      relative risk for melanoma in the general population has been difficult because
      they occur infrequently. We addressed this issue using a novel population-based
      case-control study design in which "cases" have incident second- or higher-order
      melanomas [multiple primary melanoma (MPM)] and "controls" have incident first
      primary melanoma [single primary melanoma (SPM)]. Participants were ascertained
      from nine geographic regions in Australia, Canada, Italy, and United States. In
      the 1,189 MPM cases and 2,424 SPM controls who were eligible and available for
      analysis, the relative risk of a subsequent melanoma among patients with
      functional mutations who have an existing diagnosis of melanoma, after
      adjustments for age, sex, center, and known phenotypic risk factors, is estimated
      to be 4.3 (95% confidence interval, 2.3-7.7). The odds ratio varied significantly
      depending on the type of mutation involved. The results suggest that the relative
      risk of mutation carriers in the population may be lower than currently believed
      and that different mutations on the CDKN2A gene may confer substantially
      different risks of melanoma.

PMID- 16896044
TI  - A phase I study of myo-inositol for lung cancer chemoprevention.
AB  - INTRODUCTION: A phase I, open-label, multiple dose, dose-escalation clinical
      study was conducted to assess the safety, tolerability, maximum tolerated dose,
      and potential chemopreventive effect of myo-inositol in smokers with bronchial
      dysplasia. MATERIALS AND METHODS: Smokers between 40 and 74 years of age with
      >or= 30 pack-years of smoking history and one or more sites of bronchial
      dysplasia were enrolled. A dose escalation study ranging from 12 to 30 g/d of myo
      inositol for a month was first conducted in 16 subjects to determine the maximum
      tolerated dose. Ten new subjects were then enrolled to take the maximum tolerated
      dose for 3 months. The potential chemopreventive effect of myo-inositol was
      estimated by repeat autofluorescence bronchoscopy and biopsy. RESULTS: The
      maximum tolerated dose was found to be 18 g/d. Side effects, when present, were
      mild and mainly gastrointestinal in nature. Using the regression rate of the
      placebo subjects from a recently completed clinical trial with the same
      inclusion/exclusion criteria as a comparison, a significant increase in the rate
      of regression of preexisting dysplastic lesions was observed (91% versus 48%; P =
      0.014). A statistically significant reduction in the systolic and diastolic blood
      pressures by an average of 10 mm Hg was observed after taking 18 g/d of myo
      inositol for a month or more. CONCLUSION: myo-Inositol in a daily dose of 18 g
      p.o. for 3 months is safe and well tolerated. The potential chemopreventive
      effect as well as other health benefits such as reduction in blood pressure
      should be investigated further.

PMID- 16896045
TI  - Cancer after total joint arthroplasty: a meta-analysis.
AB  - BACKGROUND: Some epidemiologic and laboratory studies have suggested that total
      joint arthroplasty could increase the risk of cancer. In this meta-analysis, we
      attempt to clarify the association of joint arthroplasty with subsequent cancer
      incidence. METHODS: We identified population-based studies reporting standardized
      incidence ratios (SIR) for cancer following large joint arthroplasty. After
      summing the observed and expected numbers of cases across all qualifying studies,
      we calculated SIRs for all cancers, and for those at 28 anatomic sites. Latency
      analysis involving 175,166 patients characterized short-term and long-term cancer
      associations. RESULTS: The analyses included 1,435,356 person-years of follow-up
      and 20,045 cases of cancer. Overall cancer risk among patients with arthroplasty
      was equal to that for the general population. The relative risk of lung cancer,
      reduced in the first 5 years after arthroplasty, increased significantly over
      time to approach that of the general population. Risks for all sites in the
      luminal gastrointestinal tract were significantly reduced by 10% to 20%; with
      relative risks that were generally stable over time. Increased risks were seen
      for cancer of the prostate (SIR, 1.12; 95% confidence interval, 1.08-1.16);
      similar relative risks were seen in each time period after the procedure. For
      melanoma, relative risks increased with follow-up to a SIR of 1.43 (95%
      confidence interval, 1.13-1.79) for 10 or more years after arthroplasty. There
      was a similar delayed emergence of increased risks for cancers of the urinary
      tract and oropharynx. The relative risk for bone cancer decreased with time after
      the procedure. CONCLUSIONS: There does not seem to be an overall increased risk
      of cancer following total joint arthroplasty. Although the risks of prostate
      cancer and melanoma seem to be elevated, there is no obvious mechanism for these
      associations. Reductions in risk for some malignancies may not be causal.

PMID- 16896046
TI  - Validity and reliability of adult recall of past sun exposure in a case-control
      study of multiple sclerosis.
AB  - BACKGROUND: Measurement of past sun exposure through recall by adults has the
      potential for measurement error. We aimed to investigate aspects of validity and
      reliability of self-reported past sun exposure. METHODS: A population-based case
      control study was conducted in Tasmania on 136 cases with multiple sclerosis and
      272 age- and sex-matched community controls. Repeat interviews on 52 cases and 52
      controls were done on average 11 weeks after the initial interview. Sun exposure
      was assessed by questionnaire and lifetime calendar. Other measurements included
      serum 25-hydroxyvitamin D, actinic damage, and skin phenotype. RESULTS: There was
      an association between recent sun exposure and serum vitamin D (time in the sun:
      r = 0.22, P < 0.01; activities outside: r = 0.31, P < 0.01 for controls) and
      between lifetime sun exposure and actinic damage [correlation between 0.34 (P <
      0.01) and 0.17 (P = 0.01) for controls]. The test-retest weighted kappa statistic
      of self-reported sun exposure ranged from 0.43 to 0.74. Recall of
      childhood/adolescent sun exposure by standardized questioning was no less
      reproducible than recall of recent adult sun exposure and no less reliable when
      made with the calendar method. Comparing the questionnaire and calendar method,
      the measures of childhood/adolescent sun exposure had a similar predictive
      validity for multiple sclerosis. CONCLUSIONS: The results of this study provide
      further evidence that adults are able to recall past sun exposure with shown
      validity and reliability and present information about the possible reasons for
      the good reliability of recalled sun exposure measures.

PMID- 16896047
TI  - Merkel cell carcinoma and multiple primary cancers.
AB  - Merkel cell carcinoma (MCC) is an aggressive neuroendocrine tumor of the skin for
      which causative factors remain largely unknown. The site-specific risks of
      multiple primary cancers associated with MCC, which may provide insight into
      etiologic influences, have not been quantified in large population-based studies.
      We estimated the long-term risk of subsequent primary tumors after a first
      primary MCC (1,306 patients) and the risk of second primary MCC following other
      first primary cancers (2,048,739 patients) within 11 population-based cancer
      registries which report to the National Cancer Institute's Surveillance,
      Epidemiology, and End Results Program (1986-2002). Patients with first primary
      MCC were at significantly increased risk of developing a subsequent cancer
      [standardized incidence ratio (SIR), 1.22; 95% confidence intervals (95% CI),
      1.01-1.45; observed (O = 122)], with significant excesses restricted to the first
      year after diagnosis (SIR, 1.71; 95% CI, 1.21-2.33; O = 39). Significantly
      elevated site-specific risks were observed for cancers of salivary gland (SIR,
      11.55; 95% CI, 2.32-33.76; O = 3), biliary sites other than liver and gallbladder
      (SIR, 7.24; 95% CI, 1.46-21.16; O = 3), and non-Hodgkin lymphoma (SIR, 2.56; 95%
      CI, 1.23-4.71; O = 10). Nonsignificantly increased risks of 2-fold or higher were
      seen for chronic lymphocytic leukemia, and cancers of the small intestine and
      brain. A significantly increased 1.36-fold risk (95% CI, 1.19-1.55; O = 221) of
      MCC as a second primary malignancy was observed among patients with all other
      first primary cancers taken together. In particular, significant 3- to 7-fold
      excesses of MCC followed multiple myeloma (SIR, 3.70; 95% CI, 1.01-9.47; O = 4),
      chronic lymphocytic leukemia (SIR, 6.89; 95% CI, 3.77-11.57; O = 14), non-Hodgkin
      lymphoma (SIR, 3.37; 95% CI, 1.93-5.47; O = 16), and malignant melanoma (SIR,
      3.05; 95% CI, 1.74-4.95; O = 16). Although enhanced medical surveillance may play
      a role, increased reciprocal risks suggest that MCC may share etiologic
      influences with other malignancies. Heightened awareness of the associations of
      lymphohematopoietic malignancies with MCC may facilitate early clinical
      recognition.

PMID- 16896048
TI  - Ovarian volume: determinants and associations with cancer among postmenopausal
      women.
AB  - Clinical studies have reported associations between ovarian stromal hyperplasia
      and the diagnosis of hormonally related tumors such as endometrial cancer. To
      assess the hypothesis that characteristics of benign ovaries among postmenopausal
      women are related to risk for breast, endometrial, and colon cancer, we analyzed
      systematically collected transvaginal ultrasound data for participants enrolled
      in the screening arm of the Prostate, Lung, Colorectal and Ovarian Cancer
      Screening Trial. Among women without cancer, median ovarian volume declined with
      age from 1.25 cm3 for women between ages 55 and 59 years to 1.0 cm3 for those
      between ages 65 and 69 years. African American and Caucasian women had larger
      median ovarian volumes than Asians. Larger ovarian volume was also associated
      with the highest quartiles of height and weight and ever having smoked. After
      adjusting for race, age, parity, body mass, smoking, and hormone use, women with
      median ovarian volumes >or=3.0 cm3 were at increased risk for breast cancer [odds
      ratio (OR), 1.42; 95% confidence interval (95% CI), 1.11-1.70], endometrial
      cancer (OR, 1.97; 95% CI, 1.12-3.48), and colon cancer (OR, 2.00; 95% CI, 1.25
      3.21). Significant trends of risk with increasing volume were found only for
      breast and endometrial cancers. We conclude that large ovaries among
      postmenopausal women may represent a marker of risk for hormonally related
      tumors. Confirmation of these findings in future studies, including analyses of
      serum hormone levels and tissues, may provide insights into hormonal
      carcinogenesis among older women.

PMID- 16896049
TI  - Flavonoids and colorectal cancer in Italy.
AB  - Because of their several biological activities, flavonoids may have an important
      role in explaining the protective effects of vegetables, fruit, and, possibly,
      tea against cancer. The potential relation between flavonoids and colorectal
      cancer risk was investigated using data from a multicentric Italian case-control
      study, including 1,953 cases of colorectal cancers (1,225 colon cancers and 728
      rectal cancers) and 4,154 hospital controls admitted for acute nonneoplastic
      diseases. We have applied recently published data on the composition of foods and
      beverages, in terms of six principal classes of flavonoids, on dietary
      information collected through a validated food-frequency questionnaire. Odds
      ratios (OR) were estimated by multiple logistic regression models, including
      terms for sex, age, study center, family history of colorectal cancer, education,
      alcohol consumption, body mass index, physical activity, and energy intake. A
      reduced risk of colorectal cancer was found for increasing intake of isoflavones
      (OR, 0.76, for the highest versus the lowest quintile, P(trend) = 0.001),
      anthocyanidins (OR, 0.67, P(trend) < 0.001), flavones (OR, 0.78, P(trend) =
      0.004), and flavonols (OR, 0.64, P(trend) < 0.001). No significant association
      was found for flavan-3-ols (OR, 0.98), flavanones (OR, 0.96), and total
      flavonoids (OR, 0.97). The estimates did not substantially differ for colon and
      rectal cancers, as well as in strata of sex, age, and body mass index. The
      findings of this large study provide support for an inverse association of
      selected classes of flavonoids with colorectal cancer risk.

PMID- 16896050
TI  - MDM2 SNP309 and SNP354 are not associated with lung cancer risk.
AB  - A single nucleotide polymorphism (SNP) in the MDM2 promoter (a T to G exchange at
      nucleotide 309) has been found to be associated with tumor formation. Publication
      of this null report is important because an association between MDM2 SNP309 and
      lung cancer was previously reported in two independent studies. Our findings
      suggest that MDM2 SNP309 is not a strong factor in lung carcinogenesis. In
      addition, this is the first MDM2 SNP309 report on a population consisting of
      Caucasians in the United States and African-Americans. A strength of the study
      design is that the controls consist of both population and hospital controls.

PMID- 16896051
TI  - Lung cancer chemoprevention: a randomized, double-blind trial in Linxian, China.
AB  - We examined the effect of supplementation with four different combinations of
      vitamins and minerals in the prevention of lung cancer mortality among 29,584
      healthy adults from Linxian, China. In accord with a partial factorial design,
      the participants were randomly assigned to take either a vitamin/mineral
      combination or a placebo for 5.25 years. The combinations tested in this trial
      were as follows: factor A, retinol and zinc; factor B, riboflavin and niacin;
      factor C, ascorbic acid and molybdenum; factor D, beta-carotene, alpha
      tocopherol, and selenium. Lung cancer deaths (n = 147) identified during the
      trial period (1986-1991) and 10 years after the trial ended (1991-2001) were the
      study outcome. No significant differences in lung cancer death rates were found
      for any of the four combinations of supplements tested in this study, using log
      rank tests (all P values are >0.20) or Cox proportional hazards models adjusted
      for age, sex, commune, and other treatments. No significant interactions were
      seen for age, sex, or smoking status. Supplementation with combinations of
      vitamins and minerals at nutrient-repletion levels for 5.25 years did not reduce
      lung cancer mortality in this nutrient-inadequate population in Linxian, China.

PMID- 16896052
TI  - No increased risk of breast cancer associated with alcohol consumption among
      carriers of BRCA1 and BRCA2 mutations ages <50 years.

PMID- 16896054
TI  - Asthma patient education opportunities in predominantly minority urban
      communities.
AB  - Disenfranchised ethnic minority communities in the urban United States experience
      a high burden of asthma. Conventional office-based patient education often is
      insufficient to promote proper asthma management and coping practices responsive
      to minority patients' environments. This paper explores existing and alternative
      asthma information and education sources in three urban minority communities in
      western New York State to help design other practical educational interventions.
      Four focus groups (n = 59) and four town hall meetings (n = 109) were conducted
      in one Hispanic and two black communities. Focus groups included adult asthmatics
      or caretakers of asthmatics, and town meetings were open to all residents. A
      critical theory perspective informed the study. Asthma information and education
      sources, perceptions of asthma and ways of coping were elicited through semi
      structured interviews. Data analysis followed a theory-driven immersion
      crystallization approach. Several asthma education and information resources from
      the health care system, media, public institutions and communities were
      identified. Intervention recommendations highlighted asthma workshops that
      recognize participants as teachers and learners, offer social support, promote
      advocacy, are culturally appropriate and community-based and include health care
      professionals. Community-based, group health education couched on people's
      experiences and societal conditions offers unique opportunities for patient
      asthma care empowerment in minority urban communities.

PMID- 16896053
TI  - High risk of human immunodeficiency virus in men who have sex with men with
      herpes simplex virus type 2 in the EXPLORE study.
AB  - The relation between herpes simplex virus type 2 (HSV-2) and human
      immunodeficiency virus (HIV) acquisition was evaluated among 4,295 high-risk, HIV
      negative men who have sex with men in an intensive behavioral intervention
      (colloquially referred to as "EXPLORE") study in the United States from 1999 to
      2003. Sexual behavior data were obtained by computer-assisted self-interview, and
      sera were collected semiannually for HIV and HSV-2 serology. HSV-2 infection was
      classified as "recent incident" (at the first HSV-2 seropositive visit), "remote
      incident" (within 24 months of the first positive visit), and "prevalent" (for
      visits >24 months after the first HSV-2 positive visit). Baseline HSV-2
      prevalence was 20.3%. HSV-2 incidence was 1.9 (95% confidence interval (CI): 1.6,
      2.2) per 100 person-years; significant risk factors were African-American race,
      unprotected receptive anal intercourse, an HIV-positive male sex partner, and six
      or more male partners in the prior 6 months. The behavioral intervention did not
      reduce HSV-2 acquisition (adjusted hazard ratio (HR) = 1.2, 95% CI: 0.9, 1.6).
      Overall HIV incidence was 1.9 (95% CI: 1.7, 2.2) per 100 person-years. HIV risk
      was elevated among men who have sex with men with recent incident HSV-2 (adjusted
      HR = 3.6, 95% CI: 1.7, 7.8), remote incident HSV-2 (adjusted HR = 1.7, 95% CI:
      0.8, 3.3), and prevalent HSV-2 (adjusted HR = 1.5, 95% CI: 1.1, 2.1) infection
      compared with HSV-2 seronegative participants. HIV intervention strategies
      targeting HSV-2 prevention and suppression among men who have sex with men should
      be evaluated.

PMID- 16896055
TI  - An assessment of occupational health care in the Netherlands (1996-2005).
AB  - BACKGROUND: The extensive Dutch occupational health care system of the past
      decade has not led to the desired outcomes, namely, a decrease of work
      absenteeism and the associated costs. AIM: To assess the differences between in
      house and external occupational health care services in the process quality of
      occupational health care provided. METHODS: In total, 26 interviews were
      conducted with chief executive officers of occupational health services (OHS).
      The responses and other relevant policy documents were analysed and described. A
      key component of this process was to compare differences between in-house and
      external services. RESULTS: Notable differences in quality were found to exist
      between in-house and external occupational health care systems, with the in-house
      occupational health care services offering the highest process quality.
      CONCLUSION: Our findings suggest that the effectiveness of OHS is mainly
      dependent on their structure (in-house versus external) and on economic factors
      (profit driven versus not for profit).

PMID- 16896056
TI  - Current research on co-occurring substance-use disorder in schizophrenia.

PMID- 16896057
TI  - Perception of causality in schizophrenia spectrum disorder.
AB  - Patients with schizophrenia spectrum disorders often maintain deviating views on
      cause-effect relationships, especially when positive and disorganization symptoms
      are manifest. Altered perceived causality is prominent in delusional ideation, in
      ideas of reference, and in the mentalizing ability (theory of mind [ToM]) of
      patients. Perceiving causal relationships may be understood either as higher
      order cognitive reasoning or as low-level information processing. In the present
      study, perception of causality was investigated as a low-level, preattentional
      capability similar to gestalt-like perceptual organization. Thirty-one patients
      (24 men and 7 women with mean age 27.7 years) and the same number of healthy
      control subjects matched to patients with respect to age and sex were tested. A
      visual paradigm was used in which 2 identical discs move, from opposite sides of
      a monitor, steadily toward and then past one another. Their coincidence generates
      an ambiguous, bistable percept (discs either "stream through" or "bounce off" one
      another). The bouncing perception, ie, perceived causality, is enhanced when
      auditory stimuli are presented at the time of coincidence. Psychopathology was
      measured using the Positive and Negative Syndrome Scale. It was found that
      positive symptoms were strongly associated with increased perceived causality and
      disorganization with attenuated perceived causality. Patients in general were not
      significantly different from controls, but symptom subgroups showed specifically
      altered perceived causality. Perceived causality as a basic preattentional
      process may contribute to higher order cognitive alterations and ToM
      deficiencies. It is suggested that cognitive remediation therapy should address
      both increased and reduced perception of causality.

PMID- 16896058
TI  - Mercury abolishes neurotrophic factor-stimulated Jak-STAT signaling in nerve
      cells by oxidative stress.
AB  - Mercury is a potent neurotoxin that can delay neurological development in
      neonates, and has been proposed to be an environmental risk factor for several
      neurodegenerative conditions. The mechanisms by which environmental factors may
      influence the propagation of neurodegenerative diseases are not yet well
      delineated. However, it is known that neurons require trophic factor support for
      maintenance and survival following traumatic physical and toxic insults. We found
      that divalent mercury (HgCl(2)) inhibited ciliary neurotrophic factor and
      interferon-gamma receptor-mediated Janus tyrosine kinase (Jak)/signal transducers
      and activators of transcription (STAT) pathway activation in SK-N-BE(2)-C
      neuroblastoma cell cultures, but did not inhibit the fibroblast growth factor
      receptor tyrosine kinase. Results of dichlorofluorescein experiments showed
      increased levels of oxidative stress in HgCl(2)-treated cells that was similar in
      magnitude to that caused by treatment with H(2)O(2). The antioxidant agents
      glutathione, N-acetylcysteine, and sodium ascorbate each protected neurons
      against HgCl(2)-induced inhibition of STAT activation. HgCl(2) also inhibited Jak
      STAT signaling in cultures of chick retina neurons, but did not affect signaling
      in nonneuronal HepG2 cells and chick skeletal myotubes. The specific inhibition
      of growth factor-mediated Jak-STAT signaling pathways in neurons by HgCl(2)
      induced oxidative stress offers a new mechanism by which mercury may produce
      neurotoxic symptoms in the developing nervous system, promote neurodegeneration
      in mature neurons, and inhibit recovery following neurotrauma.

PMID- 16896059
TI  - Nuclear translocation of endonuclease G and apoptosis-inducing factor during
      acetaminophen-induced liver cell injury.
AB  - Mitochondrial dysfunction and internucleosomal DNA fragmentation are well
      recognized features of acetaminophen (AAP)-induced hepatocyte cell death.
      However, the endonucleases responsible for this effect have not been identified.
      Apoptosis-inducing factor (AIF) and endonuclease G are nucleases located in the
      intermembrane space of mitochondria. AIF is thought to trigger chromatin
      condensation and induce cleavage of DNA into high molecular weight fragments (50
      300 kb), and endonuclease G can produce oligonucleosomal DNA fragments.
      Therefore, the objective of this investigation was to test the hypothesis that
      endonuclease G and AIF could be involved in AAP-induced nuclear DNA
      fragmentation. Using immunofluorescence microscopy, it was shown that in primary
      cultured mouse hepatocytes, endonuclease G and AIF translocated to the nucleus
      between 3 and 6 h after exposure to 5 mM AAP. In contrast, other mitochondrial
      intermembrane proteins such as cytochrome c or the second mitochondria-derived
      activator of caspases (Smac) did not accumulate in the nucleus. The translocation
      of AIF and endonuclease G correlated with mitochondrial dysfunction as indicated
      by the progressive loss of the mitochondrial membrane potential (measured with
      the JC-1 assay) and the appearance of nuclear DNA fragments in the cytosol
      (determined by an anti-histone ELISA). Pretreatment with 20mM N-acetylcysteine
      prevented mitochondrial dysfunction, the nuclear translocation of endonuclease G
      and AIF, and the nuclear DNA fragmentation. The data support the conclusion that
      endonuclease G and AIF translocate to the nucleus in response to AAP-induced
      mitochondrial dysfunction and may be responsible, at least in part, for the
      initial DNA fragmentation during AAP hepatotoxicity.

PMID- 16896060
TI  - Challenges and opportunities in proteomics data analysis.
AB  - Accurate, consistent, and transparent data processing and analysis are integral
      and critical parts of proteomics workflows in general and for biomarker discovery
      in particular. Definition of common standards for data representation and
      analysis and the creation of data repositories are essential to compare,
      exchange, and share data within the community. Current issues in data processing,
      analysis, and validation are discussed together with opportunities for improving
      the process in the future and for defining alternative workflows.

PMID- 16896061
TI  - Serum peptidome patterns that distinguish metastatic thyroid carcinoma from
      cancer-free controls are unbiased by gender and age.
AB  - Serum peptidomics is a special form of functional proteomics. The small number of
      blood proteins that are the source of most prominent peptides in human serum
      serve as a substrate pool for commonly occurring and/or cancer-derived proteases.
      Exoprotease activities in particular, when superimposed on the ex vivo
      coagulation and complement degradation pathways, contribute to generation of not
      only cancer-specific but also "cancer type"-specific serum peptides. Following
      development of a unique, semiautomated serum peptide profiling platform and after
      completing investigations to eliminate common experimental bias, we have now
      studied possible effects of gender and age on serum peptidomes of 200 healthy men
      and women, ages 20-80, and of 60 patients (30 men and 30 women) with metastatic
      thyroid carcinomas. Extensive MALDI-TOF MS and data analysis suggested negligible
      contributions of both age and gender to the serum peptidome patterns except that
      healthy men and women under 35 years, but not older individuals, could be
      distinguished with approximately 70% accuracy. Considering the more advanced age
      of most patients, this finding is unlikely to interfere with peptidomics analysis
      of most cancers. By examining patient samples and age/gender-matched controls
      followed by variability analysis of either demographic or disease (versus
      control) groups, we could conclusively rule out demographic bias. An optimized,
      12-peptide ion thyroid cancer signature was then developed, enabling
      classification of an independent validation set with 95% sensitivity and 95%
      specificity (binomial confidence intervals, 75.1-99.9%). Ten of these peptides
      had previously been assigned to signature patterns of other solid tumor cancers.
      One of the two newly discovered peptides was dehydro-Ala(3)-fibrinopeptide A. As
      we expand this study to include hundreds of thyroid cancer patients, the peptide
      signature will be adjusted, further validated, and then evaluated in a clinical
      setting used either independently or in combination with existing markers.

PMID- 16896062
TI  - Rat cytochrome P450 2C11 in liver microsomes involved in oxidation of anesthetic
      agent propofol and deactivated by prior treatment with propofol.
AB  - Propofol (2,6-diisopropylphenol) is a widely-used anesthetic agent attributable
      to its rapid biotransformation. Liver microsomal cytochrome P450 (P450) isoforms
      involved in the biotransformation of propofol in rats and the effects of propofol
      in vivo on P450 levels in rats were investigated. Of six cDNA-expressed rat P450
      isoforms tested, CYP2B1 and CYP2C11 had high catalytic activities from 5 microM
      and 20 microM propofol concentrations, respectively. Rates of propofol
      metabolism, at a substrate concentration of 20 microM based on the reported human
      blood concentration, were decreased by intraperitoneal treatment of propofol with
      male rats, in contrast to a strong induction by phenobarbital. Single
      intravenously administered propofol (10 mg/kg) caused the decrease of total P450
      and CYP2C contents and activities of testosterone 16alpha-hydroxylation and
      propofol metabolism in liver microsomes from male rats. The suppressive effects
      were caused by administered propofol (10 mg/kg) twice every 4 h on CYP2B
      activities such as testosterone 16beta-hydroxylation or pentoxyresorufin O
      depentylation, in addition to the strong suppression of CYP2C function by the
      single propofol treatment. These results suggest that CYP2C11, presumably
      deactivated by propofol, has an important role in propofol metabolism in rat
      liver microsomes. Repeated administration of propofol could markedly decrease the
      biotransformation of propofol via P450 deactivation.

PMID- 16896063
TI  - Clofibrate increases hepatic triiodothyronine (T3)- and thyroxine (T4)
      glucuronosyltransferase activities and lowers plasma T3 and T4 concentrations in
      pigs.
AB  - In rats, clofibrate acts as a microsomal enzyme inducer and disrupts the
      metabolism of thyroid hormones by increasing hepatic glucuronidation of
      thyroxine. Whether similar effects occur in the pig has not yet been
      investigated. This study was performed to investigate the effect of clofibrate
      treatment on metabolism of thyroid hormones in pigs. To this end, an experiment
      with 18 pigs, which were assigned to two groups, was performed. One group
      received a control diet, and the other group was fed the same diet supplemented
      with 5 g of clofibrate/kg for 28 days. Pigs treated with clofibrate had higher
      hepatic activities of T(3)- and T(4)-UDP glucuronosyltransferases (UGT) and lower
      concentrations of total and free T(4) and total T(3) in plasma than control pigs
      (P < 0.05). Weights and histology of the thyroid gland (epithelial height,
      follicle lumen diameter) did not differ between the two groups, but pigs treated
      with clofibrate had higher mRNA concentrations of various genes in the thyroid
      responsive to thyroid-stimulating hormone (TSH) such as TSH receptor, sodium
      iodine symporter, thyroid peroxidase, and cathepsin B than control pigs (P <
      0.05). Pigs treated with clofibrate also had lower hepatic mRNA concentrations of
      proteins involved in plasma thyroid hormone transport [thyroxine-binding globulin
      (P < 0.10), transthyretin (P < 0.05), and albumin (P < 0.05)] and thyroid hormone
      receptor alpha(1) (P < 0.05) than control pigs. In conclusion, this study shows
      that clofibrate treatment induces a strong activation of T(3)- and T(4)-UGT in
      pigs, leading to increased glucuronidation and markedly reduced plasma
      concentrations of these hormones, accompanied by a moderate stimulation of
      thyroid function.

PMID- 16896065
TI  - Characterization of ebastine, hydroxyebastine, and carebastine metabolism by
      human liver microsomes and expressed cytochrome P450 enzymes: major roles for
      CYP2J2 and CYP3A.
AB  - Ebastine undergoes extensive metabolism to form desalkylebastine and
      hydroxyebastine. Hydroxyebastine is subsequently metabolized to carebastine.
      Although CYP3A4 and CYP2J2 have been implicated in ebastine N-dealkylation and
      hydroxylation, the enzyme catalyzing the subsequent metabolic steps (conversion
      of hydroxyebastine to desalkylebastine and carebastine) have not been identified.
      Therefore, we used human liver microsomes (HLMs) and expressed cytochromes P450
      (P450s) to characterize the metabolism of ebastine and that of its metabolites,
      hydroxyebastine and carebastine. In HLMs, ebastine was metabolized to desalkyl-,
      hydroxy-, and carebastine; hydroxyebastine to desalkyl- and carebastine; and
      carebastine to desalkylebastine. Of the 11 cDNA-expressed P450s, CYP3A4 was the
      main enzyme catalyzing the N-dealkylation of ebastine, hydroxyebastine, and
      carebastine to desalkylebastine [intrinsic clearance (CL(int)) = 0.44, 1.05, and
      0.16 microl/min/pmol P450, respectively]. Ebastine and hydroxyebastine were also
      dealkylated to desalkylebastine to some extent by CYP3A5. Ebastine hydroxylation
      to hydroxyebastine is mainly mediated by CYP2J2 (0.45 microl/min/pmol P450; 22.5-
      and 7.5-fold higher than that for CYP3A4 and CYP3A5, respectively), whereas
      CYP2J2 and CYP3A4 contributed to the formation of carebastine from
      hydroxyebastine. These findings were supported by chemical inhibition and kinetic
      analysis studies in human liver microsomes. The CL(int) of hydroxyebastine was
      much higher than that of ebastine and carebastine, and carebastine was
      metabolically more stable than ebastine and hydroxyebastine. In conclusion, our
      data for the first time, to our knowledge, suggest that both CYP2J2 and CYP3A
      play important roles in ebastine sequential metabolism: dealkylation of ebastine
      and its metabolites is mainly catalyzed by CYP3A4, whereas the hydroxylation
      reactions are preferentially catalyzed by CYP2J2. The present data will be very
      useful to understand the pharmacokinetics and drug interaction of ebastine in
      vivo.

PMID- 16896064
TI  - Pharmacokinetics, metabolism, and routes of excretion of intravenous irofulven in
      patients with advanced solid tumors.
AB  - Irofulven is currently in Phase 2 clinical trials against a wide variety of solid
      tumors and has demonstrated activity in ovarian, prostate, gastrointestinal, and
      non-small cell lung cancer. The objectives of this study were to determine its
      pharmacokinetics and route of excretion and to characterize its metabolites in
      human plasma and urine samples after a 30-min i.v. infusion at a dose of 0.55
      mg/kg in patients with advanced solid tumors. Three patients were administered
      i.v. 100 microCi of [14C]irofulven over a 30-min infusion on day 1 of cycle 1.
      Serial blood and plasma samples were drawn at 0 (before irofulven infusion) and
      up to 144 h after the start of infusion. Urine and fecal samples were collected
      for up to 144 h after the start of infusion. The mean urinary and fecal excretion
      of radioactivity up to 144 h were 71.2 and 2.9%, respectively, indicating renal
      excretion was the major route of elimination of [14C]irofulven. The C(max), AUC(0
      infinity), and terminal half-life values for total radioactivity were 1130 ng
      Eq/ml, 24,400 ng-Eq . h/ml, and 116.5 h, respectively, and the corresponding
      values for irofulven were 82.7 ng/ml, 65.5 ng . h/ml, and 0.3 h, respectively,
      suggesting that the total radioactivity in human plasma was a result of the
      metabolites. Twelve metabolites of irofulven were detected in human urine and
      plasma by electrospray ionization/tandem mass spectrometry. Among these
      metabolites, the cyclopropane ring-opened metabolite (M2) of irofulven was found,
      and seven others were proposed as glucuronide and glutathione conjugates.

PMID- 16896066
TI  - PDZ adaptor protein PDZK2 stimulates transport activity of organic
      cation/carnitine transporter OCTN2 by modulating cell surface expression.
AB  - A part of the organic cation transporter families (OCT3, OCTN1, and OCTN2) has
      recently been identified to physically interact with PDZ (PSD95, Dlg, and ZO1)
      domain-containing proteins, although the physiological relevance of such
      interaction has not yet been fully examined. Here we have examined the
      stimulatory effect of PDZK2 [also named NaPi-Cap2 and intestinal and kidney
      enriched PDZ protein (IKEPP)] on those cation transporters. In HEK293 cells,
      coexpression with PDZK2 increased the uptake of carnitine by OCTN2 with minimal
      effect on its substrate recognition specificity, but not for transport activity
      of OCT3 or OCTN1. The stimulatory effect of PDZK2 on OCTN2 was compatible with an
      approximately 2 times increase in transport capacity and can be accounted for by
      the increase in cell surface expression of OCTN2. Coexpression of PDZK2 did not
      affect carnitine transport activity of OCTN2 with deletion of the last four amino
      acids, which were found to be important for the interaction, suggesting
      involvement of physical interaction of the two proteins in the increase of cell
      surface expression of OCTN2. In mouse kidney, colocalization of PDZK2 and OCTN2
      occurred predominantly in the region that was close to, but not the same as, the
      surface of apical membranes where OCTN2 alone was observed, suggesting the
      existence of OCTN2 in the subapical compartment that interacts with PDZK2. The
      present data have thus proposed an "intracellular pool" for OCTN2 that may be
      relevant to the stabilization of cell surface expression of OCTN2, thereby
      increasing transport activity for carnitine.

PMID- 16896067
TI  - Disposition of [14C]ruboxistaurin in humans.
AB  - Ruboxistaurin is a potent and specific inhibitor of the beta isoforms of protein
      kinase C (PKC) that is being developed for the treatment of diabetic
      microvascular complications. The disposition of [(14)C]ruboxistaurin was
      determined in six healthy male subjects who received a single oral dose of 64 mg
      of [(14)C]ruboxistaurin in solution. There were no clinically significant adverse
      events during the study. Whole blood, urine, and feces were collected at frequent
      intervals after dosing. Metabolites were profiled by high performance liquid
      chromatography with radiometric detection. The total mean recovery of the
      radioactive dose was approximately 87%, with the majority of the radioactivity
      (82.6 +/- 1.1%) recovered in the feces. Urine was a minor pathway of elimination
      (4.1 +/- 0.3%). The major route of ruboxistaurin metabolism was to the N
      desmethyl ruboxistaurin metabolite (LY338522), which has been shown to be active
      and equipotent to ruboxistaurin in the inhibition of PKC(beta). In addition,
      multiple hydroxylated metabolites were identified by liquid chromatography-mass
      spectrometry in all matrices. Pharmacokinetics were conducted for both
      ruboxistaurin and LY338522 (N-desmethyl ruboxistaurin, 1). These moieties
      together accounted for approximately 52% of the radiocarbon measured in the
      plasma. The excreted radioactivity was profiled using radiochromatography, and
      approximately 31% was structurally characterized as ruboxistaurin or N-desmethyl
      ruboxistaurin. These data demonstrate that ruboxistaurin is metabolized primarily
      to N-desmethyl ruboxistaurin (1) and multiple other oxidation products, and is
      excreted primarily in the feces.

PMID- 16896068
TI  - Porcine brain microvessel endothelial cells as an in vitro model to predict in
      vivo blood-brain barrier permeability.
AB  - The objective of the study was to establish primary cultured porcine brain
      microvessel endothelial cells (PBMECs) as an in vitro model to predict the blood
      brain barrier (BBB) permeability in vivo. The intercellular tight junction
      formation of PBMECs was examined by electron microscopy and measured by
      transendothelial electrical resistance (TEER). The mRNA expression of several BBB
      transporters in PBMECs was determined by reverse transcriptionpolymerase chain
      reaction analysis. The in vitro permeability of 16 structurally diverse
      compounds, representing a range of passive diffusion and transporter-mediated
      mechanisms of brain penetration, was determined in PBMECs. Except for the
      perfusion flow rate marker diazepam, the BBB permeability of these compounds was
      determined either in our laboratory or as reported in literature using in situ
      brain perfusion technique in rats. Results in the present study showed that
      PBMECs had a high endothelium homogeneity, an mRNA expression of several BBB
      transporters, and high TEER values. Culturing with rat astrocyte-conditioned
      medium increased the TEER of PBMECs, but had no effect on the permeability of
      sucrose, a paracellular diffusion marker. The PBMEC permeability of lipophilic
      compounds measured under stirred conditions was greatly increased compared with
      that measured under unstirred conditions. The PBMEC permeability of the 15 test
      compounds, determined under the optimized study conditions, correlated with the
      in situ BBB permeability with an r2 of 0.60. Removal of the three system L
      substrates increased the r2 to 0.89. In conclusion, the present PBMEC model may
      be used to predict or rank the in vivo BBB permeability of new chemical entities
      in a drug discovery setting.

PMID- 16896069
TI  - Tumour necrosis factor-alpha impairs chorionic gonadotrophin beta-subunit
      expression and cell fusion of human villous cytotrophoblast.
AB  - Growth factors expressed at the fetal-maternal interface modulate hormone
      expression of placental trophoblasts. The aim of this study was to investigate
      the effects of different cytokines on hCG subunit mRNA expression in
      differentiating villous cytotrophoblasts. Quantitative real-time PCR revealed a
      1.8- and 6.9-fold increase of hCG-alpha and hCG-beta mRNA levels, respectively,
      between 36 and 60 h of term trophoblast syncytialization. Compared with controls,
      neither interleukin (IL)-1beta, IL-2, IL-4, IL-6, IL-10, IL-13 and IL-15 nor
      tumour necrosis factor (TNF)-alpha significantly altered hCG-alpha mRNA
      expression. Similarly, the ILs did not affect hCG-beta transcript levels. In
      contrast, TNF-alpha suppressed hCG-beta mRNA 3.8- and 1.8-fold at 36 and 60 h of
      term trophoblast differentiation. Accordingly, hCG secretion was impaired by TNF
      alpha but not by the different ILs. Moreover, TNF-alpha reduced luciferase
      expression of reporter plasmids harbouring the proximal hCG-beta5 promoter to 35
      and 77%, respectively, in primary term trophoblasts and trophoblastic SHGPL-5
      cells. In addition, counting of nuclei in syncytialized, desmoplakin-negative
      areas revealed a 1.9-fold reduction of term trophoblast fusion in the presence of
      TNF-alpha. Similarly, floating explant cultures prepared from first trimester
      denuded villi recovered the syncytium 2.8-fold less efficiently during 72 h of
      cytokine treatment. Concomitantly, TNF-alpha impaired induction of endogenous and
      secreted hCG-beta protein levels in these cultures. The data suggest that TNF
      alpha decreases hCG-beta mRNA and protein expression by reducing gene
      transcription and trophoblast cell fusion. Suppression of these processes by TNF
      alpha could partly explain the adverse effects of the cytokine on placental
      function and pregnancy outcome.

PMID- 16896070
TI  - Multiple displacement amplification improves PGD for fragile X syndrome.
AB  - We report an improvement in the PGD test for fragile X syndrome (FXS). Recently,
      multiple displacement amplification (MDA) has been reported to yield large
      amounts of DNA from single cells. Taking into account this technique, we
      developed a new PGD test for FXS, enabling combined analysis of linked
      polymorphic markers with the study of the non-expanded CGG repeat. Single cell
      amplification efficiency was first assessed on single lymphocytes. Amplification
      rate of the different markers ranged from 85 to 95% with an allele drop-out (ADO)
      rate comprised between 7 and 34%. Using this test, eight PGD cycles were carried
      out for six couples, and 37 embryos were analysed after preliminary MDA.
      Amplification rate was increased by this technique from 41 to 66% so that embryos
      with no results were rarer (14 versus 45% without MDA). Reliability of the test
      was considerably improved by combining direct with indirect genetic analysis.
      Furthermore, in cases of fully expanded alleles too large to be amplified by PCR,
      this test gives an internal amplification control. Embryonic transfers were
      carried out in all but one PGD cycles. One biochemical and one clinical pregnancy
      resulted, and a healthy child was born. This single diagnosis procedure could be
      suitable to most patients carrying FXS.

PMID- 16896071
TI  - Molecular aspects of antitumor effects of a new platinum(IV) drug.
AB  - The new platinum(IV) complex cis,trans,cis-[PtCl(2)(CH(3)COO)(2)-(NH(3))(1
      adamantylamine)] [adamplatin(IV)] seems promising for the perspective application
      in therapy of corresponding tumors. It is therefore of great interest to
      understand details of mechanisms underlying its biological efficacy. Cellular
      uptake of the drug, alterations in the target DNA induced by platinum drugs along
      with processing of platinum-induced damage to DNA and drug inactivation by sulfur
      containing compounds belong to major pharmacological factors affecting antitumor
      effects of platinum compounds. We examined in the present work the significance
      of these factors in the mechanism of antitumor effects of adamplatin(IV) and
      compared the results with those of the parallel studies performed with
      "conventional" cisplatin. The results show that deactivation of adamplatin(IV) by
      sulfur-containing compounds (such as glutathione or metallothioneins) is likely
      to play a less significant role in the mechanism of resistance of tumor cells to
      adamplatin(IV) in contrast to the role of these reactions in the effects of
      cisplatin. Moreover, the treatment of tumor cells with adamplatin(IV) does not
      result in DNA modifications that would be markedly different from those produced
      by cisplatin. In contrast, the effects of other factors, such as enhanced
      accumulation of the drug in cells, strong inhibition of DNA polymerization by
      these adducts, lowered DNA repair, and DNA-protein cross-linking are different
      from the effects of these factors in the mechanism underlying activity of
      cisplatin. Hence, the differences between effects of adamplatin(IV) and cisplatin
      observed in the present work on molecular level may help understand the unique
      activity of adamplatin(IV).

PMID- 16896073
TI  - Vaccine trials guide pandemic plans.

PMID- 16896072
TI  - Circumventing recombination events encountered with production of a clinical
      grade adenoviral vector with a double-expression cassette.
AB  - Delivery of multiple exogenous genes into target cells is important for a broad
      range of gene therapy applications, including combined therapeutic gene
      expression and noninvasive imaging. Previous studies ( Mol Ther 4: 223-231, 2001
      ) have described the adenoviral vector RGDTKSSTR with a double-expression
      cassette that encodes herpes simplex virus thymidine kinase (HSVtk) for molecular
      chemotherapy and human somatostatin receptor subtype-2 (hSSTR2) for indirect
      imaging. In this vector, both genes are inserted in place of the E1 region of the
      adenoviral genome and expressed independently from two cytomegalovirus (CMV)
      promoters. During production of clinical-grade RGDTKSSTR, we found that the CMV
      promoters and simian virus 40 (SV40) poly(A) regions located in both expression
      cassettes provoked homologous recombination and deletion of one of the cassettes.
      To resolve this problem, we designed a strategy for substituting the duplicate
      promoters and poly(A) regions. We placed the hSSTR2 gene in the new
      Ad5.SSTR/TK.RGD vector under the control of a CMV promoter with a bovine growth
      hormone poly(A) region, whereas the SV40 promoter, enhancer, and poly(A) signal
      controlled HSVtk expression. This use of different regulatory sequences allowed
      independent expression of both transgenes from a single adenoviral vector and
      circumvented the recombination problem. Reconstruction of the vector with a
      double-expression cassette enables its use in human clinical trials.

PMID- 16896074
TI  - Safety consultant advises adopting middle ground on accountability.

PMID- 16896075
TI  - FDA's monitoring of postmarketing studies probed.

PMID- 16896076
TI  - Hospitals report Katrina-related losses to lawmakers.

PMID- 16896078
TI  - Leadership: successful alchemy.

PMID- 16896079
TI  - Lung surfactants.
AB  - PURPOSE: The pharmacology, clinical efficacy, and cost considerations of
      exogenous lung surfactants are reviewed. SUMMARY: Exogenous pulmonary
      surfactants, along with advancements in ventilatory care, have significantly
      reduced the incidence of respiratory distress syndrome (RDS) and its related
      complications in infants. The following exogenous surfactants are approved for
      the prophylaxis and treatment (rescue) of neonatal RDS: beractant, a modified
      natural surfactant; calfactant and poractant, both natural surfactants; and
      colfosceril, a synthetic surfactant that is not currently available in the United
      States. Lucinactant, a synthetic surfactant, is under investigation and received
      approvable status from the Food and Drug Administration in February 2005. The
      surfactants are delivered directly to their site of action, and only small
      amounts reach the systemic circulation. Bioavailability to the distal airways and
      alveoli depends on the method of delivery, the stage and severity of pulmonary
      disease, and the properties of the particular surfactant. According to data from
      clinical trials, the use of exogenous surfactant therapy for rescue within the
      first two hours of life appears to be as efficacious as prophylaxis in most
      premature infants. CONCLUSION: Comparative trials of surfactants have proven the
      efficacy of both synthetic and natural surfactants in the prevention and
      treatment of RDS. However, these trials have universally demonstrated greater
      reduction in the immediate need for ventilator support in infants who receive
      natural surfactants. Natural preparations cause less pneumothorax,
      bronchopulmonary dysplasia, and mortality compared with synthetic preparations.
      Synthetic agents offer the potential advantages of an unlimited supply with
      consistent pharmaceutical quality and no risk of transmitting infectious disease
      or causing immunologic sensitization.

PMID- 16896080
TI  - Every-three-week administration of darbepoetin alfa in women with chemotherapy
      associated anemia.
AB  - PURPOSE: The effectiveness of every-three-week administration of darbepoetin alfa
      in women with chemotherapy-associated anemia was evaluated. METHODS: Women
      receiving chemotherapy for gynecological tumors who had a hemoglobin
      concentration of <10 g/dL were recruited from an obstetrics and gynecology
      service. Study patients received subcutaneous darbepoetin alfa 6.75 microg/kg,
      followed by 4.5 microg/kg every three weeks for a total of up to six doses.
      Hematopoietic response and mean changes in hemoglobin concentrations were
      evaluated. The Functional Assessment in Cancer Therapy-Anemia (FACT-An) survey
      was self-administered before and after study completion to evaluate the patients'
      quality of life. RESULTS: The mean+/-S.D. age and weight for the 14 patients
      recruited (12 of whom were assessable) were 52.1+/-14 years and 64.6+/-19.8 kg,
      respectively. The mean initial and maintenance doses were 442 and 301.6 microg,
      respectively. The overall hematopoietic response was 64.3%, of which 35.7% were
      complete and 28.6% were partial. Peak response occurred at weeks 9 and 12. The
      mean+/-S.D. change in hemoglobin concentration was 1.6+/-1.51 g/dL. Treatment
      failure was predicted by week 9 (n=2). Maintenance doses were withheld if a
      patient's hemoglobin concentration exceeded 12 g/dL (n=3). The mean+/-S.D. point
      differential for FACT-An pretreatment and posttreatment scores was 5.8+/-4.71
      (n=6). CONCLUSION: Every-three-week administration of subcutaneous darbepoetin
      alfa produced a complete or partial hematopoietic response in 11 of 14 women with
      chemotherapy- associated anemia. A quality-of-life indicator generally improved
      among the 6 patients for whom posttreatment quality-of-life data were available.

PMID- 16896081
TI  - Using failure mode and effects analysis to plan implementation of smart i.v. pump
      technology.
AB  - PURPOSE: Failure mode and effects analysis (FMEA) was used to evaluate a smart
      i.v. pump as it was implemented into a redesigned medication-use process.
      SUMMARY: A multidisciplinary team conducted a FMEA to guide the implementation of
      a smart i.v. pump that was designed to prevent pump programming errors. The smart
      i.v. pump was equipped with a dose-error reduction system that included a pre
      defined drug library in which dosage limits were set for each medication.
      Monitoring for potential failures and errors occurred for three months
      postimplementation of FMEA. Specific measures were used to determine the success
      of the actions that were implemented as a result of the FMEA. The FMEA process at
      the hospital identified key failure modes in the medication process with the use
      of the old and new pumps, and actions were taken to avoid errors and adverse
      events. I.V. pump software and hardware design changes were also recommended.
      Thirteen of the 18 failure modes reported in practice after pump implementation
      had been identified by the team. A beneficial outcome of FMEA was the development
      of a multidisciplinary team that provided the infrastructure for safe technology
      implementation and effective event investigation after implementation. With the
      continual updating of i.v. pump software and hardware after implementation, FMEA
      can be an important starting place for safe technology choice and implementation
      and can produce site experts to follow technology and process changes over time.
      CONCLUSION: FMEA was useful in identifying potential problems in the medication
      use process with the implementation of new smart i.v. pumps. Monitoring for
      system failures and errors after implementation remains necessary.

PMID- 16896082
TI  - Indeterminable international normalized ratio with concurrent use of warfarin and
      gatifloxacin.

PMID- 16896083
TI  - It is time for a new Gies report.

PMID- 16896084
TI  - Oral brush biopsy technique instruction outcomes for senior dental students.
AB  - Computerized oral brush biopsy became commercially available in 1999. The
      objectives of this study were to provide senior dental students with the clinical
      competency to perform oral brush biopsy and to evaluate the extent to which
      students used this technique and the outcomes of their biopsy techniques. During
      the 2004-05 academic year, 114 senior dental students at The Ohio State
      University College of Dentistry participated in a brush biopsy instructional
      program. Brush biopsy training was part of their outreach and engagement
      experience. Technique instruction included 1) completion of thirteen interactive
      online educational modules, 2) discussion of a written protocol including
      clinical photographs and an oral pathology position paper, and 3) performance of
      a trial demonstration brush biopsy on each other. Eighty-one students submitted
      brush biopsies on clinical patients. Lesions were found in approximately one out
      of every twenty patients. Seventy-four biopsy results (91 percent) were
      diagnostic although seventeen (21 percent) were limited by suboptimal cellular
      representation and seven (9 percent) were inadequate. The high percentage (71
      percent) of students who actually applied their training in a true clinical
      setting indicates that the program was successful in providing dental students
      the information necessary to perform this procedure on their own. However, the
      number of incomplete specimens suggests the need for technique refinement and
      additional clinical experience.

PMID- 16896085
TI  - Perceptions of professionalism vary most with educational rank and age.
AB  - The purpose of this study was to assess whether the perception of what
      constitutes professionalism varies with age, discipline, gender, or educational
      level among students and faculty at the major academic health sciences center in
      West Virginia. This exploratory descriptive survey study asked participants to
      classify behaviors described in a survey as professional, unprofessional, or
      unrelated to professionalism. Results were analyzed using contingency tables. For
      2 x 2 contingency tables, test of independence of homogeneity was carried out by
      using Fisher's exact test. For tables of higher dimensions, chi square test was
      used. The survey yielded a 45 percent return rate and demonstrated that the
      perception of professionalism varied most with the level of education and age
      and, to a lesser extent, with gender and health care discipline. Undergraduates,
      females, the youngest age group (< or = 26), nursing students, and faculty other
      than dental or medical were more likely to label behavior depicted in the survey
      statements as unprofessional. The findings of this study underscore the
      complexities of the genesis of professionalism. Further study in regard to the
      teaching of professionalism is warranted.

PMID- 16896086
TI  - Proposed educational objectives for hospital-based dentists during catastrophic
      events and disaster response.
AB  - The purpose of this project was to define education and training requirements for
      hospital-based dentists to efficiently and meaningfully participate in a hospital
      disaster response. Eight dental faculty with hospital-based training and/or
      military command and CBRNE (chemical, biological, radiological, nuclear, and
      explosive) expertise were recruited as an expert panel. A consensus set of
      recommended educational objectives for hospital-based dentists was established
      using the following process: 1) identify assumptions supported by all expert
      panelists, 2) determine current advanced dental educational training
      requirements, and 3) conduct additional training and literature review by various
      panelists and discussions with other content and systems experts. Using this
      three-step process, educational objectives that the development group believed
      necessary for hospital-based dentists to be effective in treatment or management
      roles in times of a catastrophic event were established. These educational
      objectives are categorized into five thematic areas: 1) disaster systems, 2)
      triage/medical assessment, 3) blast and burn injuries, 4) chemical agents, and 5)
      biological agents. Creation of training programs to help dentists acquire these
      educational objectives would benefit hospital-based dental training programs and
      strengthen hospital surge manpower needs. The proposed educational objectives are
      designed to stimulate discussion and debate among dental, medical, and public
      health professionals about the roles of dentists in meeting hospital surge
      manpower needs.

PMID- 16896087
TI  - Interprofessional educational partnerships in school health for children with
      special oral health needs.
AB  - Dental caries is an infectious yet preventable disease that is rampant in some
      subpopulations in the United States, in particular among individuals with
      neurodevelopmental/intellectual disabilities (ND/ID). This article reports on the
      implementation and evaluation of the Louisiana State University Health Sciences
      Center (LSUHSC) School of Dentistry interprofessional school health educational
      model to improve oral health assessment and referral for children with ND/ID in
      an inner-city school system. During this project, dental hygiene students and
      elementary school nurses were paired to assess the oral health status of 255
      inner-city children with developmental disabilities, improve referral/access to
      dental care for those identified as having need, and propose dental hygiene
      curriculum changes that would incorporate participation in a "real-life public
      health setting" for those with ND/ID. Following the program, 66 percent of dental
      hygiene students said their likelihood of participating in future oral health
      programs had increased and 75 percent of school nurses rated the educational
      process as very good or excellent. Modifications in dental hygiene curricula that
      provide students with training and experience in oral health risk assessment and
      referral for people with ND/ID is recommended to address the new Commission on
      Dental Accreditation educational standards 2-18 and 2-26 (implemented January 1,
      2005) and dental standard 2-26 (implemented January 1, 2006), which state that
      dental hygiene and dental graduates must be competent in assessing the treatment
      needs of patients with special needs.

PMID- 16896088
TI  - Teaching style beliefs among U.S. and Israeli faculty.
AB  - The purpose of this study was to determine if self-reported teaching style
      beliefs were different among faculty at a U.S. and an Israeli dental school.
      Teacher-centered practices refer to beliefs that the teacher holds the subject
      matter expertise and students are generally passive learners who must be told
      what to think. Student-centered practices refer to beliefs that students must
      learn how to construct their own understanding. Student-centered teaching is
      directed towards enabling students to think about complex issues. Twenty-seven of
      fifty-eight (47.37 percent) faculty at a dental school in the United States and
      thirty of thirty-four (88 percent) Israeli dental faculty teaching in basic
      science courses completed the Teaching Behavior Preferences Survey (TBPS). The
      TBPS is a thirty-item instrument that measures two domains of teaching styles-
      teacher-centered (TC) and student-centered (SC)--and four subdomains: methods of
      instruction (MI), classroom milieu (CM), use of questions (UQ), and use of
      assessment (UA). Findings revealed that there were no significant differences in
      student-centered and teacher-centered teaching practices and methods of
      instruction, classroom milieu, and use of questions. There was a significant
      difference between the U.S. and Israeli groups in their reported use of
      assessment. The U.S. faculty reported a greater preference for student-centered
      assessment practices than did the Israeli faculty.

PMID- 16896089
TI  - Critical appraisal and positive outcome bias in case reports published in
      Brazilian dental journals.
AB  - The aim of this study was to carry out a critical appraisal to detect the
      occurrence of publication bias, specifically positive-outcome bias, in Brazilian
      dental journals. A convenience sample of twenty-eight dental journals published
      in Brazil between 1994 and 2003 was selected (564 issues containing 5,453
      articles). Each article was classified according to methodological design; 1,064
      were classified as case reports. A simple random sample of 435 articles comprised
      the final study sample and was submitted to a critical appraisal by previously
      trained raters. Although a great part of case reports achieve proper structural
      aspects, most authors did not consider important aspects that could help the
      decision making process, such as discussion of alternative approaches, limitation
      of the performed procedures, lack of long-term clinical follow-up, possible
      variations in treatment outcome, and failure to discuss limitations of study
      design. In addition, unanimous reports of successful outcomes of clinical
      interventions strongly suggest that publication of case reports was influenced by
      positive outcome bias, which may influence readers' clinical decision making
      process.

PMID- 16896090
TI  - A model of dental public health teaching at the undergraduate level in Peru.
AB  - There has been a growing interest among dental educators regarding the
      opportunities offered by community-based dental education as a means to allow
      dental students to assume their role as health professionals in the real world.
      Although several dental schools have integrated community-based education into
      their curricula, most have not engaged their students in the development of
      competencies to address dental health needs at the community level. The purpose
      of this article is to discuss the teaching-learning experiences in dental public
      health at the undergraduate level in the Faculty of Stomatology at the
      Universidad Peruana Cayetano Heredia (FS-UPCH) in Lima, Peru. The teaching
      learning activities in dental public health at the FS-UPCH consist of two well
      defined stages: experiences in low-income urban communities and experiences in
      low-income rural communities. Both stages have been designed to make it possible
      for students to acquire competency in addressing oral health needs at the
      community level as well as to enlarge and deepen their knowledge about the social
      and health situation in Peru. In community-based dental education, students are
      not only placed in community settings to treat individual patients, but also
      challenged to consider dental public health issues, including the administrative
      aspects of dental services.

PMID- 16896091
TI  - Implications of the growth of dental education in India.
AB  - By influencing the supply of trained human resources, the dental education sector
      can play a significant role in influencing policy goals of ensuring good quality
      and equitable access to oral health services in developing countries. Our
      research goal was to assess quantitatively the size of the Indian dental
      education sector, its growth over time, and the implications of this growth for
      equity and quality in oral health care. Information on the location of teaching
      institutions, the year of establishment, type of ownership, and seat capacity was
      obtained from government sources, the Dental Council of India, and websites of
      individual institutions to estimate the growth in the undergraduate dental
      education sector, including the role of the private sector from 1950 to 2005.
      Data on location of training capacity and institutions were used to assess the
      geographical distribution of undergraduate dental education capacity in India.
      Registration data on dentists, the size of available faculty relative to
      regulatory requirements, and penalties imposed on offending faculty and education
      institutions were used to assess the impact of the growing Indian dental
      education sector on graduate quality and equitable access. Dental colleges and
      enrollment capacity have grown rapidly over the five decades since 1950, mainly
      due to a growing private sector. There is regional inequality in the location of
      dental education schools in India with a bias toward economically better-off
      regions. The growth in the dental education sector has translated into increased
      overall access, although accompanied by rising inequality in access and possibly
      lower quality of dental education.

PMID- 16896093
TI  - The cover. Vegetable Garden, Overcast Morning, Eragny.

PMID- 16896094
TI  - A piece of my mind. In only an instant.

PMID- 16896095
TI  - Guidelines seek to standardize care for diseased heart valves.

PMID- 16896096
TI  - Researchers examine long-term risks of exposure to medical radiation.

PMID- 16896097
TI  - CDC panel backs routine HPV vaccination.

PMID- 16896098
TI  - Groups call truce over metabolic syndrome.

PMID- 16896099
TI  - Gender a factor to consider in weighing timing of heart transplant.

PMID- 16896100
TI  - Studies suggest dog walking a good strategy for fostering fitness.

PMID- 16896101
TI  - Prognostic index for 4-year mortality in older adults.

PMID- 16896102
TI  - Prognostic index for 4-year mortality in older adults.

PMID- 16896103
TI  - Effect of rimonabant on weight and cardiometabolic risk factors.

PMID- 16896104
TI  - Aromatase inhibitors and breast cancer treatment.

PMID- 16896105
TI  - International volunteer medicine.

PMID- 16896106
TI  - Unreported financial disclosures in a study of migraine and cardiovascular
      disease.

PMID- 16896107
TI  - Comparison of meeting abstracts and subsequent articles.

PMID- 16896108
TI  - Recalls and safety alerts affecting automated external defibrillators.
AB  - CONTEXT: Automated external defibrillators (AEDs) play a key role in the
      community resuscitation of persons with cardiac arrest and are of proven clinical
      benefit. Although AEDs are complex medical devices designed to function during
      life-threatening emergencies, little is known about their reliability.
      OBJECTIVES: To determine the number and rate of AED recalls and safety alerts, to
      identify trends in these rates, and to identify the types of malfunctions
      prompting AED and AED accessory advisories. DESIGN AND SETTING: Analysis of
      weekly US Food and Drug Administration (FDA) Enforcement Reports between January
      1996 and December 2005 was performed to identify all recalls and safety alerts
      (collectively referred to as "advisories") involving AEDs and AED accessories.
      Confirmed AED device malfunctions were identified by reviewing AED-related
      adverse events reported to the FDA. MAIN OUTCOME MEASURES: Number of AEDs and AED
      accessories subject to FDA recall or safety alert between January 1996 and
      December 2005; annual AED advisory rates; and number of confirmed fatal AED
      related device malfunctions reported to the FDA. RESULTS: During 2.78 million AED
      device-years of observation, 52 advisories (median [25th and 75th percentiles],
      4.5 [3.0 and 5.0] per year) affecting 385,922 AEDs and AED accessories were
      issued. The mean (SE) annual number of AEDs affected by advisories was 5.1 (1.5)
      devices per 100 AED device-years. Overall, 21.2% of AEDs distributed during the
      study period were recalled, most often because of electrical or software
      problems. The AED advisory rate did not significantly increase during the study
      period, although the annual number of AED advisories (P for trend =.02) and AED
      advisory devices (P for trend = .01) did increase. Confirmed fatal AED-related
      device malfunctions occurred in 370 patients. CONCLUSIONS: Automated external
      defibrillators and AED accessory advisories occur frequently and affect many
      devices. Actual AED malfunctions do occur occasionally, although the number of
      observed malfunctions is small compared with the number of lives saved by these
      important devices. As the prevalence of AEDs continues to increase, the number of
      devices affected by advisories can also be expected to increase. Efforts should
      be directed at developing a reliable system to locate and repair potentially
      defective devices in a timely fashion.

PMID- 16896109
TI  - Collaborative analysis of alpha-synuclein gene promoter variability and Parkinson
      disease.
AB  - CONTEXT: Identification and replication of susceptibility genes for Parkinson
      disease at the population level have been hampered by small studies with
      potential biases. Alpha-synuclein (SNCA) has been one of the most promising
      susceptibility genes, but large-scale studies have been lacking. OBJECTIVE: To
      determine whether allele-length variability in the dinucleotide repeat sequence
      (REP1) of the SNCA gene promoter is associated with Parkinson disease
      susceptibility, whether SNCA promoter haplotypes are associated with Parkinson
      disease, and whether REP1 variability modifies age at onset. DESIGN, SETTING, AND
      PARTICIPANTS: We performed a collaborative analysis of individual-level data on
      SNCA REP1 and flanking markers in patients with Parkinson disease and controls.
      Study site recruitment, data collection, and analyses were performed between
      April 5, 2004, and December 31, 2005. Eighteen participating sites of a global
      genetics consortium provided clinical data. Genotyping was performed for SNCA
      REP1, -770, and -116 markers at individual sites; however, each site also
      provided 20 DNA samples for regenotyping centrally. MAIN OUTCOME MEASURES:
      Measures included estimations of Hardy-Weinberg equilibrium in controls; a test
      of heterogeneity; analyses for association of single variants or haplotypes; and
      survival analyses for age at onset. RESULTS: Of the 18 sites, 11 met stringent
      criteria for concordance with Hardy-Weinberg equilibrium and low genotyping error
      rate. These 11 sites provided complete data for 2692 cases and 2652 controls.
      There was no heterogeneity across studies (P>.60). The SNCA REP1 alleles differed
      in frequency for cases and controls (P<.001). Genotypes defined by the 263 base
      pair allele were associated with Parkinson disease (odds ratio, 1.43; 95%
      confidence interval, 1.22-1.69; P<.001 for trend). Multilocus haplotypes differed
      in frequency for cases and controls (global score statistic, P<.001). Two-loci
      haplotypes were associated with Parkinson disease only when they included REP1 as
      one of the loci. However, genotypes defined by REP1 alleles did not modify age at
      onset (P = .55). CONCLUSION: This large-scale collaborative analysis demonstrates
      that SNCA REP1 allele-length variability is associated with an increased risk of
      Parkinson disease.

PMID- 16896111
TI  - Adherence to antiretroviral therapy in sub-Saharan Africa and North America: a
      meta-analysis.
AB  - CONTEXT: Adherence to antiretroviral therapy is a powerful predictor of survival
      for individuals living with human immunodeficiency virus (HIV) and AIDS. Concerns
      about incomplete adherence among patients living in poverty have been an
      important consideration in expanding the access to antiretroviral therapy in sub
      Saharan Africa. OBJECTIVE: To evaluate estimates of antiretroviral therapy
      adherence in sub-Saharan Africa and North America. DATA SOURCES: Eleven
      electronic databases were searched along with major conference abstract databases
      (inclusion dates: inception of database up until April 18, 2006) for all English
      language articles and abstracts; and researchers and treatment advocacy groups
      were contacted. Study Selection and Data Abstraction To best reflect the general
      population, studies of mixed populations in both North America and Africa were
      selected. Studies evaluating specific populations such as men only, homeless
      individuals, or drug users, were excluded. The data were abstracted in duplicate
      on study adherence outcomes, thresholds used to determine adherence, and
      characteristics of the populations. A random-effects meta-analysis was performed
      in which heterogeneity was examined using multivariable random-effects logistic
      regression. A sensitivity analysis was performed using Bayesian methods. DATA
      SYNTHESIS: Thirty-one studies from North America (28 full-text articles and 3
      abstracts) and 27 studies (9 full-text articles and 18 abstracts) from sub
      Saharan Africa were included. African studies represented 12 sub-Saharan
      countries. Of the North American studies, 71% used patient self-report to assess
      adherence; this was true of 66% of the African assessments. Studies reported
      similar thresholds for adherence monitoring (eg, 100%, >95%, >90%, >80%). A
      pooled analysis of the North American studies (17,573 patients total) indicated a
      pooled estimate of 55% (95% confidence interval, 49%-62%; I2, 98.6%) of the
      populations achieving adequate levels of adherence. Our pooled analysis of
      African studies (12,116 patients total) indicated a pooled estimate of 77% (95%
      confidence interval, 68%-85%; I2, 98.4%). Study continent, adherence thresholds,
      and study quality were significant predictors of heterogeneity. Bayesian analysis
      was used as an alternative statistical method for combining adherence rates and
      provided similar findings. CONCLUSION: Our findings indicate that favorable
      levels of adherence, much of which was assessed via patient self-report, can be
      achieved in sub-Saharan African settings and that adherence remains a concern in
      North America.

PMID- 16896110
TI  - Effectiveness of Haemophilus influenzae type b Conjugate vaccine introduction
      into routine childhood immunization in Kenya.
AB  - CONTEXT: Haemophilus influenzae type b (Hib) conjugate vaccine is not perceived
      as a public health priority in Africa because data on Hib disease burden and
      vaccine effectiveness are scarce. Hib immunization was introduced in Kenyan
      infants in 2001. OBJECTIVE: To define invasive Hib disease incidence and Hib
      vaccine program effectiveness in Kenya. DESIGN, SETTING, AND PATIENTS: Culture
      based surveillance for invasive Hib disease at Kilifi District Hospital from 2000
      through 2005 was linked to demographic surveillance of 38,000 children younger
      than 5 years in Kilifi District, Kenya. Human immunodeficiency virus (HIV)
      infection and Hib vaccination status were determined for children with Hib
      disease admitted 2002-2005. INTERVENTIONS: Introduction of conjugate Hib vaccine
      within the routine childhood immunization program at ages 6, 10, and 14 weeks
      beginning November 2001. MAIN OUTCOME MEASURES: Incidence of culture-proven Hib
      invasive disease before and after vaccine introduction and vaccine program
      effectiveness. RESULTS: Prior to vaccine introduction, the median age of children
      with Hib was 8 months; case fatality was 23%. Among children younger than 5
      years, the annual incidence of invasive Hib disease 1 year before and 1 and 3
      years after vaccine introduction was 66, 47, and 7.6 per 100,000, respectively.
      For children younger than 2 years, incidence was 119, 82, and 16 per 100,000,
      respectively. In 2004-2005, vaccine effectiveness was 88% (95% confidence
      interval, 73%-96%) among children younger than 5 years and 87% (95% confidence
      interval, 66%-96%) among children younger than 2 years. Of 53 children with Hib
      admitted during 2002-2005, 29 (55%) were age-ineligible to have received vaccine,
      12 (23%) had not been vaccinated despite being eligible, and 12 (23%) had
      received 2 or more doses of vaccine (2 were HIV positive). CONCLUSIONS: In Kenya,
      introduction of Hib vaccine into the routine childhood immunization program
      reduced Hib disease incidence among children younger than 5 years to 12% of its
      baseline level. This impact was not observed until the third year after vaccine
      introduction.

PMID- 16896112
TI  - Refusal of care: patients' well-being and physicians' ethical obligations: "but
      doctor, I want to go home".
AB  - Honoring patients' wishes becomes difficult when doing so threatens their well
      being. In this article, the case of a hospitalized elderly woman is presented.
      The patient, ready for discharge, insists on returning home, yet she is bedbound
      and lacks adequate social support and financial resources to manage safely. The
      medical team, troubled by this situation, requests an ethics consultation. The
      article discusses several issues related to the difficult ethical problem posed
      by this case, including a brief historical review of the patient's role in
      decision making, current thinking about patients' rights vis-a-vis patients' well
      being, assessing patients' capacity to make sound decisions, consideration of
      physician values, and, finally, responding to patients' refusal of care.

PMID- 16896113
TI  - Tracking progress in patient safety: an elusive target.

PMID- 16896115
TI  - JAMA patient page. Automated external defibrillators.

PMID- 16896114
TI  - Automated external defibrillators--device reliability and clinical benefits.

PMID- 16896116
TI  - First Brazilian experience with the use of artemether-lumefantrine (Coartem) a
      fixed-dosed ACT combination.

PMID- 16896117
TI  - High reinfection rate and treatment failures in children treated with amodiaquine
      for falciparum malaria in Muheza villages, Northeastern Tanzania.
AB  - In May 2003, we studied amodiaquine (AQ) efficacy in children < 5 years of age
      with uncomplicated falciparum malaria in Magoda and Mpapayu (with insecticide
      treated nets [ITNs]) and Mgome (without ITNs) in Muheza, Tanzania. The trial
      involved 28 days of follow-up, and data were adjusted by polymerase chain
      reaction (PCR) genotyping of msp1 and msp2 genes. Additionally, Pfcrt codon 72-76
      polymorphisms were studied by PCR and sequence-specific oligonucleotide probe
      (SSOP) ELISA. In 54 cases with complete follow-up, a significant difference in
      late treatment failure (LTF) rates was seen (60.7% in ITN versus 88.5% in non-ITN
      villages, P = 0.02) before PCR correction. However, after PCR correction, 23
      cases (60.5%) were confirmed as reinfections, giving a true LTF rate of 21.4%
      (6/28) and 34.6% (9/26) in the above settings, respectively. Frequency of Pfcrt
      CVIET haplotype mutation pretreatment was high (97.0%); the remaining samples
      were CVMNK. We conclude that AQ alone is no longer effective in the study area.

PMID- 16896118
TI  - Parasitic co-infections: does Ascaris lumbricoides protect against Plasmodium
      falciparum infection?
AB  - A controlled randomized trial of antihelminthic treatment was undertaken in 1996
      1997 in a rural area of Madagascar where populations were simultaneously infected
      with Ascaris lumbricoides and Plasmodium falciparum. Levamisole was administered
      bimonthly to 164 subjects, randomized on a family basis, whereas 186 were
      controls. While levamisole proved to be highly effective in reducing Ascaris egg
      loads in the treated group (P < 10(-3) at all bimonthly visits), subjects more
      than 5 years of age, treated with levamisole had a significant increase in their
      P. falciparum densities compared with controls (P = 0.02), whereas there was no
      effect of anti-helminthic treatment on children 6 months to 4 years of age. The
      demonstration of a clear negative interaction between Ascaris infection and
      malaria parasite density has important implications. Single community therapy
      programs to deliver treatments against several parasitic infections could avoid
      an increase of malaria attacks after mass treatment of ascariasis.

PMID- 16896120
TI  - Malaria prevention during pregnancy: assessing the disease burden one year after
      implementing a program of intermittent preventive treatment in Koupela District,
      Burkina Faso.
AB  - The World Health Organization recommends that pregnant women in malaria-endemic
      areas receive >or= 2 doses of intermittent preventive treatment with sulfadoxine
      pyrimethamine (IPTp/SP) in the second and third trimesters of pregnancy to
      prevent maternal anemia, placental parasitemia, and low birth weight (LBW). In
      2001, a program evaluation in Koupela District, Burkina Faso demonstrated that
      despite widespread use of chloroquine chemoprophylaxis, the burden of malaria
      during pregnancy remained high. In 2003, the Burkina Faso Ministry of Health
      piloted a program of IPTp/SP (three doses) and accelerated distribution of
      insecticide-treated nets (ITN) to pregnant women in Koupela District. In 2004, a
      follow-up program evaluation was conducted. Coverage with >or= 1 doses of IPTp/SP
      was high among women attending antenatal clinics (ANCs) (96.2%) and delivery
      units (DUs) (93.5%); ITN ownership was moderately high (ANC = 53.9%, DU = 61.6%).
      In multivariate analysis, >or= 1 dose of IPTp/SP was associated with a
      significant reduction in the prevalence of peripheral parasitemia at ANCs (risk
      ratio [RR] = 0.49, P = 0.008), >or= 2 doses of IPTp/SP were associated with a
      reduction in the prevalence of placental parasitemia (RR = 0.56, P = 0.02), and
      three doses of IPTp/SP were associated with a reduced risk of LBW (RR = 0.51, P =
      0.04). The proportions of women at ANCs with peripheral parasitemia and anemia
      were significantly lower in 2004 than in 2001 (RR = 0.53, P = 0.001 and RR =
      0.78, P = 0.003, respectively). The proportions of women at DUs with peripheral
      and placental parasitemia were also significantly lower in 2004 than in 2001 (RR
      = 0.66, P < 0.0001 and RR = 0.71, P = 0.0002, respectively). These data suggest
      that a package of IPTp/SP and ITNs is effective in reducing the burden of malaria
      during pregnancy in Burkina Faso.

PMID- 16896119
TI  - Serum antibody levels to glycosylphosphatidylinositols in specimens derived from
      matched Malian children with severe or uncomplicated Plasmodium falciparum
      malaria and healthy controls.
AB  - Neutralizing antibodies to glycosylphosphatidylinositols (GPIs), which are
      Plasmodium falciparum surface protein anchor molecules implicated in malaria
      pathogenesis, are thought to protect against symptomatic malaria. Index cases of
      severe malaria in Malian children 3 months to 14 years of age were matched by age
      and residence to uncomplicated malaria and healthy controls. Serum antibodies to
      GPI (IgM and IgG) were measured at the time of severe malaria and after the
      malaria transmission season. The mean optical density values for IgM and IgG
      antibodies were higher in children with severe or uncomplicated malaria compared
      with healthy controls. Similarly, higher percentages of children with IgM and IgG
      antibodies to GPI were observed in the severe malaria group compared with matched
      healthy controls. IgG antibody levels to GPI were highest among children with
      cerebral malaria and children who died. The IgG antibody levels to GPI peaked
      during periods of malaria transmission and decreased after malaria transmission
      ended. A direct correlation between age and parasitemia and IgG antibodies to GPI
      was observed. In summary, higher levels of IgM and IgG antibodies to GPI in young
      children were associated with disease severity and were short-lived.

PMID- 16896121
TI  - Detection sensitivity and quantitation of Plasmodium falciparum var gene
      transcripts by real-time RT-PCR in comparison with conventional RT-PCR.
AB  - Antigenic variation in Plasmodium falciparum erythrocyte membrane protein 1,
      caused by a switch in transcription of the encoding var gene, is an important
      feature of malaria. In this study, we quantified the relative abundance of var
      gene transcripts present in P. falciparum parasite clones using real-time reverse
      transcription-polymerase chain reaction (RT-PCR) and conventional RT-PCR combined
      with cloning and sequencing, with the aim of directly comparing the results
      obtained. When there was sufficient abundance of RNA for the real-time RT-PCR
      assay to be operating within the region of good reproducibility, RT-PCR and real
      time RT-PCR tended to identify the same dominant transcript, although some
      transcript-specific issues were identified. When there were differences in the
      estimated relative amounts of minor transcripts, the RT-PCR assay tended to
      produce higher estimates than real-time RT-PCR. These results provide valuable
      information comparing RT-PCR and real-time RT-PCR analysis of samples with small
      quantities of RNA as might be expected in the analysis of field or clinical
      samples.

PMID- 16896122
TI  - Variation in malaria transmission intensity in seven sites throughout Uganda.
AB  - Knowledge of the baseline malaria transmission in a given environment is
      important to guide malaria control interventions. However, in Uganda, recent
      information on malaria transmission intensity is lacking. Therefore, a 1-year
      entomological study was conducted in seven ecologically different sites
      throughout the country to assess spatial and temporal patterns in malaria
      transmission intensity. Anopheles gambiae sensu stricto was the main vector in
      five of the seven study sites, and An. funestus was the most important vector in
      the two other sites. In a peri-urban village, An. arabiensis contributed
      substantially to malaria transmission. Clear differences in annual entomological
      inoculation rates (AEIR) were observed between the study sites, ranging from 4
      infective bites per person per year in the southwestern part of the country to
      >1,500 infective bites per person per year in a swampy area near the Nile River.
      Between villages with parasite prevalences of >or= 80% in children between 1 and
      9 years old, a 4-fold difference in AEIR was observed. Based on the observed
      behavior of the vectors, insecticide-treated bed nets will be highly effective in
      controlling malaria. However, in the high transmission areas, additional measures
      will be needed to reduce the malaria burden to acceptable levels.

PMID- 16896123
TI  - Impact of single and multiple residual sprayings of pyrethroid insecticides
      against Triatoma dimidiata (Reduviiade; Triatominae), the principal vector of
      Chagas disease in Jutiapa, Guatemala.
AB  - This study investigated the impact of single, double, and triple insecticide
      sprayings on indoor infestation of Triatoma dimidiata in Jutiapa, Guatemala. Up
      to three successive insecticide sprayings were applied in villages, where the
      indoor infestation index was > 5% before each spraying round or located adjacent
      to the persistently infested villages. Among 64 villages with single spraying,
      the mean indoor infestation index reduced from 20.8% to 1.4% after 12 months, but
      rose to 8.1% after 33 months. In 40 double-sprayed villages, it decreased from
      41.9% to 11.9% by the first spraying and to 4.8% by the second spraying. For 12
      villages with triple spraying, it reduced from 40.6% to 13.2%, 10.9%, and 4.1%
      through each spraying round. Geographic analysis showed that originally highly
      infested villages were spatially clustered and were likely to remain infested
      after the sprayings. Indoor infestation of T. dimidiata can be controlled with
      less than three rounds of spraying.

PMID- 16896124
TI  - DNA profiling of human blood in anophelines from lowland and highland sites in
      western Kenya.
AB  - We used polymerase chain reaction (PCR)-based DNA profiling to determine the
      person from whom Anopheles funestus and An. gambiae collected in natural human
      habitations obtained their blood meals. Less than 20% of human hosts contributed
      to > 50% of all blood meals, and 42% were not bitten at all, including people in
      the age group bitten most often. As expected, bites were unevenly distributed by
      age (young adults > older adults > children). Use of untreated bed nets by
      adults, but not children, seemed to redirect bites to children. Multiple blood
      meals in a single gonotrophic cycle occurred frequently enough to be
      epidemiologically important (14% for An. funestus and 11% for An. gambiae).
      Mosquitoes that did not bite a person who slept in the collection house can
      affect estimation of entomological risk. Mosquito-human interactions did not
      differ across ecologically and epidemiologically distinct highland and lowland
      sites.

PMID- 16896126
TI  - Oviposition behavior of female Anopheles gambiae in western Kenya inferred from
      microsatellite markers.
AB  - Anopheles gambiae females in a relatively isolated hut and all larvae from larval
      habitats within 100 m of the hut were collected in August 2001 in western Kenya.
      Among 42 aquatic habitats, 16 had A. gambiae larvae. Two hundred fifty larvae and
      58 adults were genotyped using nine microsatellite markers to infer sibling
      relationship between the larvae and maternity between the females and larvae. The
      pairwise genetic relatedness of A. gambiae larvae per habitat ranged from -0.4112
      to 0.9375, indicating that full siblings, half siblings, and genetically
      unrelated individuals presented at those habitats with multiple larvae. From a
      likelihood analysis, it was estimated that 56.6% of females had larvae in
      multiple habitats. These results substantiate that one A. gambiae female uses
      multiple breeding sites for oviposition, and thus, average genetic relatedness
      for breeding sites with high larval populations tends to be low.

PMID- 16896125
TI  - Limited diversity of Anopheles darlingi in the Peruvian Amazon region of Iquitos.
AB  - Anopheles darlingi is the most important malaria vector in the Amazon basin of
      South America, and is capable of transmitting both Plasmodium falciparum and P.
      vivax. To understand the genetic structure of this vector in the Amazonian region
      of Peru, a simple polymerase chain reaction (PCR)-based test to identify this
      species of mosquito was used. A random amplified polymorphic DNA-PCR was used to
      study genetic variation at the micro-geographic level in nine geographically
      separate populations of An. darlingi collected in areas with different degrees of
      deforestation surrounding the city of Iquitos. Within-population genetic
      diversity in nine populations, as quantified by the expected heterozygosity
      (H(E)), ranged from 0.27 to 0.32. Average genetic distance (F(ST)) among these
      populations was 0.017. These results show that the nine studied populations are
      highly homogeneous, suggesting that strategies can be developed to combat this
      malaria vector as a single epidemiologic unit.

PMID- 16896127
TI  - Rapid assay to identify the two genetic forms of Culex (Culex) pipiens L.
      (Diptera: Culicidae) and hybrid populations.
AB  - A previously developed method to identify members of the Culex pipiens complex
      exploiting polymorphisms in a nuclear intron (acetylcholinesterase [ACE] based
      assay) cannot differentiate the two forms of Cx. pipiens: form pipiens and form
      molestus. Notably, the two forms seem to differ extensively in behavior and
      physiology and likely have very different epidemiologic importance. Because they
      are morphologically indistinguishable, molecular methods are critical for the
      evaluation of their relative importance. Although the two forms of Cx. pipiens
      have been distinguished using a panel of microsatellite loci, such a protocol is
      laborious and expensive. We developed a rapid assay based on polymorphisms in the
      flanking region of a microsatellite locus. Used in conjunction with the ACE
      assay, this new assay allows the identification of pure and hybrid populations of
      the two Cx. pipiens forms as well as those including Cx. quinquefasciatus. We
      discuss the usefulness of the method as well as limitations to its application.

PMID- 16896128
TI  - Are cytochrome B gene sequencing and polymorphism-specific polymerase chain
      reaction as reliable as multilocus enzyme electrophoresis for identifying
      Leishmania spp. from Argentina?
AB  - Recently, two techniques, polymerase chain reaction (PCR) amplification and
      sequencing of cytochrome b gene (cyt b gene sequencing) and polymorphism-specific
      PCR (PS-PCR) were recommended for Leishmania species identification. Before this
      study, however, the accuracy of these methods had not been tested against the
      multilocus enzyme electrophoresis, the current gold standard technique on this
      task. Therefore, a trial was done for the first time to compare the results
      obtained by these techniques, using 17 Argentinean Leishmania stocks in
      independent assays. For all the stocks examined, the same results at species
      level were obtained by the three techniques. Among them, 14 were assigned to L.
      (Viannia) braziliensis, and three to L. (V.) guyanensis. The two techniques, cyt
      b gene sequencing and PS-PCR, were able to distinguish between all the proven
      species responsible for leishmaniases in Argentina. Thus, both techniques were
      validated and could be used independently for the species designation of
      Leishmania parasites in the country.

PMID- 16896129
TI  - Multilocus enzyme electrophoresis and cytochrome B gene sequencing-based
      identification of Leishmania isolates from different foci of cutaneous
      leishmaniasis in Pakistan.
AB  - Seventeen Leishmania stocks isolated from cutaneous lesions of Pakistani patients
      were studied by multilocus enzyme electrophoresis and by polymerase chain
      reaction amplification and sequencing of the cytochrome b (Cyt b) gene. Eleven
      stocks that expressed nine zymodemes were assigned to L. (Leishmania) major. All
      of them were isolated from patients in the lowlands of Larkana district and Sibi
      city in Sindh and Balochistan provinces, respectively. The remaining six,
      distributed in two zymodemes (five and one), isolated from the highland of Quetta
      city, Balochistan, were identified as L. (L.) tropica. The same result at species
      level was obtained by the Cyt b sequencing for all the stocks examined. No clear
      cut association between the clinical features (wet or dry type lesions) and the
      Leishmania species involved was found. Leishmania (L.) major was highly
      polymorphic compared with L. (L.) tropica. This difference may be explained by
      the fact that humans may act as a sole reservoir of L. (L.) tropica in
      anthroponotic cycles; however, many wild mammals can be reservoirs of L. (L.)
      major in zoonotic cycles.

PMID- 16896130
TI  - Concomitant early mucosal and cutaneous leishmaniasis in Brazil.
AB  - Mucosal leishmaniasis (ML) is often clinically silent until reaching a highly
      advanced state. In this prospective study, 6 of 220 patients with early cutaneous
      leishmaniasis were diagnosed with mucosal involvement by otorhinolaryngological
      examination (a rate similar to the reported rate of late ML). Detection of early
      ML may represent an important strategy in preventing severe mucosal destruction
      in human leishmaniasis.

PMID- 16896131
TI  - Pseudomonas aeruginosa otochondritis complicating localized cutaneous
      leishmaniasis: prevention of mutilation by early antibiotic therapy.
AB  - A patient with an ulcerated cutaneous leishmaniasis of the pinna had suppurative
      otochondritis after a first unsuccessful course of treatment with meglumine
      antimoniate. Although the Leishmania ulceration healed after a second course of
      meglumine antimoniate, and despite three oral dicloxacillin or pristinamycin
      courses, the otochondritis extended and an abscess developed. Pus from the
      abscess revealed a pure culture of Pseudomonas aeruginosa. Five days of oral
      ciprofloxacin plus rifampin led to a marked improvement. The P. aeruginosa
      isolate was sensitive to ciprofloxacin but fully resistant to rifampin. Healing
      with minimal mutilation was obtained at the end of a six-week course of multiple
      antibiotic therapy. Pseudomonas aeruginosa otochondritis was a co-factor of
      cartilage mutilation in this patient. Thus, infection with P. aeruginosa should
      be promptly treated when present in tender cutaneous or mucosal leishmaniasis
      lesions near cartilaginous areas.

PMID- 16896132
TI  - Impact of climate variability in the occurrence of leishmaniasis in northeastern
      Colombia.
AB  - Previous studies have shown that variation in the distribution of vectors
      associated to the transmission of Leishmania species may be related to climatic
      changes. However, the potential implications of these ecological changes in human
      health need to be further defined in various endemic populations where
      leishmaniasis carries a substantial burden of disease such as in Northeastern
      Colombia. Herein, we report the impact of El Nino Southern Oscillation climatic
      fluctuations during 1985-2002 in the occurrence of cases of leishmaniasis in two
      northeastern provinces of Colombia. During this period, we identified that during
      El Nino, cases of leishmaniasis increased, whereas during La Nina phases,
      leishmaniasis cases decreased. This preliminary data show how climatic changes
      influence the occurrence of leishmaniasis in northeastern Colombia and
      contributes to the growing body of evidence that shows that the incidence of
      vector-borne diseases is associated with annual changes in weather conditions.

PMID- 16896133
TI  - Morbidity indicators of Schistosoma mansoni: relationship between infection and
      anemia in Ugandan schoolchildren before and after praziquantel and albendazole
      chemotherapy.
AB  - The potential relationship between Schistosoma mansoni and anemia was examined
      using data obtained by the Schistosomiasis Control Initiative (SCI) before
      (baseline) and 1 year after (follow-up) a chemotherapeutic treatment program in
      Uganda. Changes in hemoglobin (Hb) levels in 2,788 children in relation to their
      schistosomiasis and/or hookworm infection intensity category and baseline anemia
      status were analyzed. At baseline, significant predictors of childhood anemia
      were intensities of S. mansoni and hookworm infection. At follow-up, moderate or
      heavy hookworm as well as heavy S. mansoni infections were important. Children
      heavily infected with S. mansoni or hookworm had significantly lower Hb counts at
      baseline compared with those not infected. Among anemic children at the baseline
      survey, a significant increase in Hb counts of 0.834 g/dL after treatment was
      found. Our results suggest that anemia is associated with schistosomiasis and
      hookworm in Ugandan children and that such anemia shows a significant improvement
      after chemotherapy.

PMID- 16896135
TI  - Dual infection of animal hosts with different Echinococcus species in the eastern
      Qinghai-Tibet plateau region of China.
AB  - The eastern Qinghai-Tibet plateau of China is a highly endemic region of
      echinococcosis where Echinococcus granulosus sensu stricto (sheep strain),
      Echinococcus multilocularis, and Echinococcus shiquicus are distributed
      sympatrically. We developed a polymerase chain reaction-based restriction
      fragment length polymorphism (PCR-RFLP) method for the identification of the
      three species in this region. The PCR-RFLP showed the dual infection of animals
      with different Echinococcus spp. The first case was a domestic dog concurrently
      infected with adults of E. granulosus and E. multilocularis. The second case was
      a plateau pika (Ochotona curzoniae) harboring metacestodes of E. multilocularis
      and E. shiquicus in the liver. The high susceptibility of some mammalian hosts to
      the parasites and the high prevalence of the three co-endemic species probably
      increase the chance of mixed infections in the eastern Tibetan plateau.

PMID- 16896134
TI  - Triclabendazole and its two main metabolites lack activity against Schistosoma
      mansoni in the mouse model.
AB  - Some have claimed that triclabendazole, a safe and efficacious drug for the
      treatment of fascioliasis, also exhibits antischistosomal properties, but results
      are conflicting. We assessed the effect of triclabendazole and its two main
      metabolites against two different strains of Schistosoma mansoni harbored in
      mice. Low worm burden reductions (18.6-35.9%) were observed in mice infected with
      an Egyptian strain of S. mansoni and treated with a single dose of 120 mg/kg 3
      days before infection or single/double doses of 120-200 mg/kg 7 weeks after
      infection. Triclabendazole failed to significantly reduce hepatic and intestinal
      tissue egg loads, and eggs of all developmental stages were observed.
      Administration of 400 mg/kg of either triclabendazole, triclabendazole sulphone,
      or triclabendazole sulfphoxide to mice infected with a Liberian strain of S.
      mansoni resulted in worm burden reductions < 10%. In comparison, high worm burden
      reductions (82-100%) were observed in S. mansoni-infected mice treated with
      single oral doses of 400, 500, or 500 mg/kg twice a day praziquantel, regardless
      of the S. mansoni strain. We conclude that triclabendazole and its main
      metabolites display weak and inconsistent schistosomicidal activities.

PMID- 16896136
TI  - Plant-borne human contamination by fascioliasis.
AB  - Contamination by fasciolids takes place through ingestion of metacercariae
      attached to vegetables. Experimental studies were performed with plant-made foods
      suggesting a role in human contamination in Iran and on the usefulness of
      potassium permanganate as a preventive tool for killing metacercariae attached to
      vegetables used in salads in Egypt. In the foods assayed, although viability
      decreases with time, a high percentage of the metacercariae were still alive 2
      and 4 weeks after preparation. Infection of laboratory animals proved that
      metacercariae kept their infectivity. The 5-minute tests of potassium
      permanganate effects showed that metacercarial viability was not affected even at
      the very high doses of 300, 600, and 1,200 mg/L. Careful, subsequent washing of
      leaves and vegetables with water is therefore needed after its application. A
      review on similar studies performed with metacercariae belonging to fasciolid and
      other trematode species affecting humans is included.

PMID- 16896137
TI  - A familial case of visceral larva migrans after ingestion of raw chicken livers:
      appearance of specific antibody in bronchoalveolar lavage fluid of the patients.
AB  - We report a familial case of visceral larva migrans (VLM) caused by Toxocara
      canis larvae. Patient 1 was a 45-year-old man who presented to our university
      hospital complaining of mild fever, general fatigue, and headache. Patient 2 was
      a 71-year-old man and was the father of Patient 1; he presented complaining of
      cough and hyper-viscous white sputum. Laboratory data from both patients showed
      extensive eosinophilia, their chest X-ray findings revealed multiple pulmonary
      infiltrates, and their bronchoalveolar lavage fluid (BALF) showed an elevated
      eosinophil count. The diagnosis of VLM was made based on a positive result in a
      serological test using T. canis larval excretory-secretory both in the serum and
      BALF. T. canis larvae were identified in meat that was prepared from chicken
      taken from the same source as that ingested. This is the first report to identify
      antibodies in BALF in patients with VLM.

PMID- 16896138
TI  - Is the human-infecting Diphyllobothrium pacificum a valid species or just a South
      American population of the holarctic fish broad tapeworm, D. latum?
AB  - Using ITS2 gene sequences, the validity of the tapeworm Diphyllobothrium
      pacificum (Nybelin, 1931), infecting humans on the Pacific coast of South America
      and in Japan, was assessed. ITS2 sequences of this cestode differed markedly
      (sequence similarity 79.0-80.2%) from those of the most common human-infecting
      cestode, the broad fish tapeworm Diphyllobothrium latum (L.), as well as other
      four species of Diphyllobothrium, including potential human parasites (D.
      cordatum, D. dendriticum, and D. lanceolatum) and two species of Spirometra
      (sequence similarity 77.5-81.9%). Interspecific sequence similarity between all
      but one (D. pacificum) species was 86.1-99.6%, whereas individual isolates of D.
      dendriticum and D. ditremum exhibited intraspecific sequence similarity of 97.0
      98.0% and 98.2-99.9%, respectively. Phylogenetic trees constructed from ITS2
      sequences show a markedly distant position of D. pacificum from other species
      analyzed and also indicate the possible paraphyly of Spirometra.

PMID- 16896139
TI  - Mycobacterium ulcerans disease (Buruli ulcer) in a rural hospital in Bas-Congo,
      Democratic Republic of Congo, 2002-2004.
AB  - Buruli ulcer (BU), which is caused by Mycobacterium ulcerans, is an important
      disabling skin disease. Its prevalence is highest in west and central Africa. We
      report an apparent resurgence of BU in the Bas-Congo Province, Democratic
      Republic of Congo. During a 28-month period in 2002-2004, the rural hospital of
      the Institut Medical Evangelique at Kimpese admitted 51 patients suspected of
      having BU. Bacteriologic, molecular biologic, and histopathologic studies
      confirmed BU in 36 of these patients. Extensive clinical data, treatment
      outcomes, and socioeconomic correlations are summarized. Osteomyelitis was an
      important complication. A multidisciplinary approach to BU control in the Bas
      Congo is proposed, aimed primarily at active case detection.

PMID- 16896142
TI  - Is classic Kaposi's sarcoma endemic in Peru?: report of a case in an indigenous
      patient.
AB  - Kaposi's sarcoma (KS) has been classified in four clinical variants (classic or
      Mediterranean; endemic or African; epidemic or AIDS-related; iatrogenic or
      immunosuppression-related). Human herpesvirus 8 (HHV-8), has been found in all
      these variants. We herein discuss the unusual presentation of a 53-year-old
      indigenous patient with purplish-brown nodular lesions on lower extremities, and
      miliary tuberculosis. ELISA-HIV tests were negative and immunohistochemistry
      (IHC) of the tumor tissue was positive for HHV-8. This is the first reported case
      in which the presence of HHV-8 was evidenced by means of IHC techniques in Peru.
      We also review all available Peruvian literature of classic KS, a disease that
      has been frequently reported in indigenous population of Peru since 1968, making
      this country a possible endemic zone of classic KS.

PMID- 16896140
TI  - The serologic prevalence of Q fever (Coxiella burnetii) complement-fixing
      antibodies in the Peninsular bighorn sheep of Southern California.
AB  - Q fever is a rare illness in the Southern California desert. During the past 34
      years only 6 patients have been diagnosed with the disease at the Eisenhower
      Medical Center, a referral center for much of the desert and surrounding
      mountains. In all but 2 instances, Q fever was identified in patients who have
      been in contact with imported domestic sheep who are brought to the desert to
      graze and lamb in the fall and winter. The sheep are sent back to Idaho, Wyoming,
      and Montana in the spring. With frequent infection by Coxiella burnetii
      established in domestic sheep, we elected to study the prevalence of complement
      fixing antibodies to Coxiella burnetii in native bighorn sheep who reside in the
      lower levels of the mountains surrounding the desert. From 1992 to 1999, of 268
      serum samples drawn from male and female lambs and adult sheep, 27 tested
      positive (10%), which is strikingly low when compared with Dall sheep in Alaska
      (12 of 15), kangaroos, wild rabbits, and brown rats. Because changes have been
      made in Peninsular bighorn sheep habitat since the animals were listed as
      endangered in 1998, further follow-up in Q fever serology testing will be of
      interest.

PMID- 16896141
TI  - Preliminary observations on Mycobacterium spp. in dairy cattle in Ecuador.
AB  - This study evaluated bovine tuberculosis in Mejia canton, a major dairy cattle
      production region in Ecuador. Randomly selected cattle (1,012 from 59 farms)
      classified according to herd size were tested by the single tuberculin test
      (STT). Sixty days later, positive reactors were tested again by the comparative
      tuberculin test (CTT). In addition, tissue samples from two STT-CTT-positive
      reactors detected on a farm were obtained in a local slaughterhouse and analyzed
      bacteriologically. A total of 4.24% of the cattle were positive in the STT and
      3.85% were positive in the CTT, with the highest number (7.95%) in large herds
      versus 3.4% in medium herds and 0.3% in small herds. Mycobacterium bovis was
      isolated from mesenteric lymph nodes and lungs of one animal. A 16S ribosomal RNA
      based polymerase chain reaction confirmed culture results and differentiated
      mycobacteria other than M. tuberculosis. This study confirms the zoonotic
      importance of tuberculosis in Ecuadorian dairy cattle with herd size likely to be
      a crucial parameter in the prevalence of the disease. The implementation of a
      national control program is necessary and should be based on the detection of
      positive cattle by STT in combination with CTT.

PMID- 16896143
TI  - Detection and isolation of highly pathogenic H5N1 avian influenza A viruses from
      blow flies collected in the vicinity of an infected poultry farm in Kyoto, Japan,
      2004.
AB  - During the outbreak of highly pathogenic avian influenza that occurred in Tamba
      Town, Kyoto Prefecture in 2004, a total of 926 flies were collected from six
      sites within a radius of 2.3 km from the poultry farm. The H5 influenza A virus
      genes were detected from the intestinal organs, crop, and gut of the two blow fly
      species, Calliphora nigribarbis and Aldrichina grahami, by reverse transcription
      polymerase chain reaction for the matrix protein (M) and hemagglutinin (HA)
      genes. The HA gene encoding multiple basic amino acids at the HA cleavage site
      indicated that this virus is a highly pathogenic strain. Based on the full-length
      sequences of the M, HA, and neuraminidase (NA) segments of virus isolates through
      embryonated chicken eggs, the virus from C. nigribarbis (A/blow
      fly/Kyoto/93/2004) was characterized as H5N1 subtype influenza A virus and shown
      to have > 99.9% identities in all three RNA segments to a strain from chickens
      (A/chicken/Kyoto/3/2004) and crows (A/crows/Kyoto/53/2004) derived during this
      outbreak period in Kyoto in 2004. Our results suggest it is possible that blow
      flies could become a mechanical transmitter of H5N1 influenza virus.

PMID- 16896144
TI  - Yellow fever vaccine-associated viscerotropic disease (YEL-AVD) and
      corticosteroid therapy: eleven United States cases, 1996-2004.
AB  - During 1996 through 2004, 29 cases of yellow fever vaccine-associated
      viscerotropic disease (YEL-AVD) have been reported worldwide; 17 were fatal.
      Stress-dose corticosteroid (SDS) therapy has recently been found to improve
      survival among patients with septic shock but benefit for the treatment of YEL
      AVD patients in septic shock is unknown. We retrospectively reviewed medical
      records of 11 U.S. YEL-AVD cases reported to the Vaccine Adverse Event Reporting
      System (VAERS) from 1996 through 2004. Four of 11 case-patients received SDS; 3
      of these 4 (75%) survived. Seven patients did not receive SDS and 2 (29%)
      survived. Altered mental status was documented on admission for 5 of the 11
      patients; 4 of these 5 did not receive SDS and died, whereas one received SDS and
      survived. The use of stress-dose steroids might be a factor that influenced the
      survival of these YEL-AVD patients and should be further evaluated in the
      management of both YEL-AVD and wild-type yellow fever septic shock.

PMID- 16896145
TI  - Enhanced early West Nile virus infection in young chickens infected by mosquito
      bite: effect of viral dose.
AB  - Mosquito transmission of arboviruses potentially affects the course of viral
      infection in the vertebrate host. Studies were performed to determine if viral
      infection differed in chickens infected with West Nile virus (WNV) by mosquito
      bite or needle inoculation. Mosquito-infected chickens exhibited levels of
      viremia and viral shedding that were up to 1,000 times higher at 6, 12, and 24
      hours post-feeding (PF) compared with those inoculated with 10(3) PFU by needle.
      Follow-up studies were conducted to determine if enhanced early infection was due
      to a higher viral dose inoculated by mosquitoes. Needle inoculation with
      successively higher doses of WNV led to higher early viremia and viral shedding;
      a dose >or= 10(4) PFU by needle was required to attain the high early viremia
      observed in mosquito-infected chickens. Mosquitoes inoculated WNV at this level
      as estimated by feeding on a hanging drop of blood (mean: 10(2.5), range: 10(0.7)
      10(4.6) PFU). These results indicate that enhanced early infection in mosquito
      infected chickens may be explained by higher viral dose delivered by mosquitoes.
      On the other hand, chickens infected by multiple mosquitoes (N = 3-11) had
      viremic titers that were 25-50 times higher at 6 and 12 hours PF than in chickens
      infected by a single mosquito, suggesting that viral dose is not the only factor
      involved in enhanced early infection. The likelihood that enhanced early
      infection in mosquito-infected chickens is due to a higher viral dose inoculated
      by mosquitoes and/or other factors (saliva, inoculation location, or viral
      source) is discussed.

PMID- 16896146
TI  - West Nile virus in mosquitoes of northern Ohio, 2003.
AB  - From June 19, 2003 to August 18, 2003, we surveyed the mosquitoes of Oberlin, OH,
      for West Nile Virus (WNV) infection using reverse transcriptase-polymerase chain
      reaction. A total of 12,055 mosquitoes, representing 17 species or species groups
      and 4 genera, were collected in gravid traps at seven sites throughout the city,
      with Culex pipiens/restuans being the most abundant and showing the highest
      minimum infection rate (MIR) of 0.78. This represents a decrease in WNV enzootic
      activity from the previous year. Both Cx. pipiens/restuans abundance and MIR
      increased significantly with date. However, we found no correlation between Cx.
      pipiens/restuans abundance and MIR.

PMID- 16896147
TI  - Does the roosting behavior of birds affect transmission dynamics of West Nile
      virus?
AB  - The potential role of many urban passerine birds in the transmission of West Nile
      virus (WNV) is well-documented by studies on host competency, seroprevalence in
      wild birds, and identification of vector blood meal source. In contrast, the
      impact of bird behavior on transmission dynamics is largely unexplored. Bird
      roosting (perching) behavior may be a critical component regulating WNV
      transmission because of the crepuscular/nocturnal feeding behavior of Culex
      mosquitoes, the primary vectors of WNV. We used radio telemetry to determine the
      roosting behavior of American crows (Corvus brachyrhynchos) and northern
      cardinals (Cardinalus cardinalus). On average, healthy crows moved slightly
      shorter distances between roosts than viremic crows, 1,038.3 meters versus
      1,255.5 meters, while cardinals only moved 54.7 meters. Given the average
      movements of crows and cardinals between roosts, crows, which are viremic for
      five days, could spread the virus throughout a mean +/- SE area of 20.84 +/- 0.79
      km(2), while viremic cardinals would, on average, only spread the virus over a
      mean +/- SE area of 0.03 +/- 0.01 km(2). Because the crow population in Illinois
      is decreasing at a rate of 11.5% per year and up to 35.6% per year in certain
      locations, crows are becoming scarce in some areas, thus reducing their role as
      wild bird sentinels. We suggest that if crows are important in dispersing WNV,
      large decreases in their abundance will shift transmission cycles to a more focal
      nature because of the differences in roosting behavior of crows compared with
      other urban birds, such as cardinals.

PMID- 16896149
TI  - Is injecting a finger with rabies immunoglobulin dangerous?
AB  - Treating potentially rabies virus infected wounds requires the injection of
      rabies immunoglobulin into and around the wounds, followed by vaccination with an
      approved tissue culture rabies vaccine. A significant number of such bite wounds
      involves fingers where there is little space for expansion. Injecting
      immunoglobulin into such areas under pressure may induce a compartment syndrome
      caused by compromising circulation. We carried out a retrospective review and a
      prospective study of patients seen with digital bite injuries and found that it
      is a safe procedure if carried out with care by experienced staff.

PMID- 16896148
TI  - Effects of immunosuppression on West Nile virus infection in hamsters.
AB  - A research study, comparing the pathogenesis of experimental West Nile virus
      (WNV) infection in immunocompetent and immunosuppressed golden hamsters, is
      described. Cyclophosphamide was used to immunosuppress the animals. The
      immunosuppressed hamsters had a prolonged period of viremia, depressed humoral
      immune response, more extensive and severe pathology, and higher fatality rate
      than the untreated immunocompetent animals. Histopathological and
      immunohistochemical studies of tissues from the two groups showed that pathologic
      changes in the untreated infected animals were confined to the brain and spinal
      cord, whereas the histopathological changes and WNV antigen distribution in the
      immunosuppressed animals were much more extensive and diffuse, involving the
      adrenal, kidney, heart and lung, and brain and spinal cord. Results of this study
      in the hamster model provide insight into the increased severity of WNV infection
      observed in immunosuppressed people.

PMID- 16896150
TI  - Hepatitis delta virus infection in mongolia: analyses of geographic distribution,
      risk factors, and disease severity.
AB  - The prevalence and risk factors for hepatitis delta virus (HDV) infection among
      Mongolian school children were assessed by detecting the antibody against HDV and
      HDV RNA, and through structured interviews. The study subjects consisted of 181
      children with the past or ongoing hepatitis B virus infection who were
      investigated during the nationwide serosurvey conducted in 2004. The prevalence
      of antibody to HDV was 6.1%, with the proportion of 13.6% among hepatitis B
      surface antigen (HBsAg)-positive subjects, all of whom had HDV RNA. Multivariate
      logistic regression analyses showed that injections (> 11 times) (odds ratio [OR]
      = 8.31, 95% confidence interval [CI] = 1.28-54.07) and blood sampling (> 3 times)
      (OR = 5.34, 95% CI = 1.12-25.53) in health care settings, hospitalization (> 3
      times) (OR = 6.20, 95% CI = 1.18-32.71), and cohabitating with patients with
      chronic hepatitis (OR = 4.57, 95% CI = 1.26-16.55) predicted the seropositivity
      for antibody to HDV. These results suggest that parenteral exposures in health
      care settings and household transmission are the main routes of HDV transmission
      among Mongolian children.

PMID- 16896151
TI  - Prognostic significance of CD20 expression in childhood B-cell precursor acute
      lymphoblastic leukemia.
AB  - CD20 expression is associated with inferior survival in adults with acute
      lymphoblastic leukemia (ALL). We analyzed the prognostic impact of CD20
      expression in 353 children with B-cell precursor ALL treated in 3 consecutive St
      Jude Total Therapy studies. CD20 expression (> 20%) was found in 169 patients
      (48%) and was more frequent in patients between 1 and 10 years of age than in
      those younger than 1 or older than 10 years (P = .001). None of 14 patients with
      MLL-AF4 expressed CD20. There was no association between CD20 expression and E2A
      PBX, TEL-AML1, ploidy, white blood cell count at diagnosis, or sex. In contrast
      to the experience in adult ALL, our patients with CD20 expression tended to have
      a better treatment outcome than those without the expression: 5-year event-free
      survival 84% +/- 2.9% versus 78% +/- 3.1% (P = .08). These data suggest that CD20
      expression is not associated with inferior outcome in pediatric patients treated
      with contemporary regimens.

PMID- 16896152
TI  - Mesenchymal stem cells display coordinated rolling and adhesion behavior on
      endothelial cells.
AB  - To explore the initial steps by which transplanted mesenchymal stem cells (MSCs)
      interact with the vessel wall in the course of extravasation, we studied binding
      of human MSCs to endothelial cells (ECs). In a parallel plate flow chamber, MSCs
      bound to human umbilical vein ECs (HUVECs) similar to peripheral-blood
      mononuclear cells (PBMCs) or CD34(+) hematopoietic progenitors at shear stresses
      of up to 2 dynes/cm(2). This involved rapid extension of podia, rolling, and
      subsequent firm adhesion that was increased when ECs were prestimulated with TNF
      alpha. MSC binding was suppressed when ECs were pretreated with function-blocking
      anti-P-selectin antibody, and rolling of MSCs was induced on immobilized P
      selectin, indicating that P-selectin was involved in this process. Preincubation
      of HUVECs with anti-VCAM-1 or of MSCs with anti-VLA-4 antibodies suppressed
      binding of MSCs to HUVECs but did not enhance inhibition by anti-P-selectin,
      indicating that both P-selectin and VCAM-1 are equally required for this process.
      Intravital microscopy demonstrated the capacity of MSCs to roll and adhere to
      postcapillary venules in vivo in a mouse model in a P-selectin-dependent manner.
      Thus, MSCs interact in a coordinated fashion with ECs under shear flow, engaging
      P-selectin and VCAM-1/VLA-4.

PMID- 16896153
TI  - Receptor-type protein tyrosine phosphatase gamma (PTPgamma), a new identifier for
      myeloid dendritic cells and specialized macrophages.
AB  - Protein tyrosine phosphatase (PTPgamma) is a receptor-like molecule with a known
      role in murine hematopoiesis. We analyzed the regulation of PTPgamma expression
      in the human hematopoietic system, where it was detected in human peripheral
      blood monocytes and dendritic cells (DCs) of myeloid and plasmacytoid phenotypes.
      Its expression was maintained during in vitro monocyte differentiation to
      dendritic cells (moDC) and was further increased after maturation with bacterial
      lipopolysaccharide (LPS), CD40L, and TNFalpha. But PTPgamma was absent when
      monocytes from the same donor were induced to differentiate in macrophages. B and
      T lymphocytes did not express PTPgamma. Rather, PTPgamma mRNA was expressed in
      primary and secondary lymphoid tissues, and the highest expression was in the
      spleen. PTPgamma was detected by immunohistochemistry in subsets of myeloid
      derived DCs and specialized macrophages (tingible bodies, sinus and alveolar
      macrophages). Classic macrophages in infective or reactive granulomatous
      reactions did not express PTPgamma. Increased PTPgamma expression was associated
      with a decreased ability to induce proliferation and interferon-gamma secretion
      in T cells by moDCs from patients with advanced pancreatic cancer. Taken
      together, these results indicate that PTPgamma is a finely regulated protein in
      DC and macrophage subsets in vitro and in vivo.

PMID- 16896154
TI  - CTLA-4 blockade decreases TGF-beta, IDO, and viral RNA expression in tissues of
      SIVmac251-infected macaques.
AB  - Regulatory T (T(reg)) cells are a subset of CD25(+)CD4(+) T cells that
      constitutively express high levels of cytotoxic T lymphocyte antigen-4 (CTLA-4)
      and suppress T-cell activation and effector functions. T(reg) cells are increased
      in tissues of individuals infected with HIV-1 and macaques infected with simian
      immunodeficiency virus (SIV(mac251)). In HIV-1 infection, T(reg) cells could
      exert contrasting effects: they may limit viral replication by decreasing immune
      activation, or they may increase viral replication by suppressing virusspecific
      immune response. Thus, the outcome of blocking T(reg) function in HIV/SIV should
      be empirically tested. Here, we demonstrate that CD25(+) T cells inhibit virus
      specific T-cell responses in cultured T cells from blood and lymph nodes of SIV
      infected macaques. We investigated the impact of CTLA-4 blockade using the anti
      CTLA-4 human antibody MDX-010 in SIV-infected macaques treated with
      antiretroviral therapy (ART). CTLA-4 blockade decreased expression of the
      tryptophan-depleting enzyme IDO and the level of the suppressive cytokine
      transforming growth factor-beta (TGF-beta) in tissues. CTLA-4 blockade was
      associated with decreased viral RNA levels in lymph nodes and an increase in the
      effector function of both SIV-specific CD4(+) and CD8(+) T cells. Therefore,
      blunting T(reg) function in macaques infected with SIV did not have detrimental
      virologic effects and may provide a valuable approach to complement ART and
      therapeutic vaccination in the treatment of HIV-1 infection.

PMID- 16896155
TI  - Involvement of suppressors of cytokine signaling in toll-like receptor-mediated
      block of dendritic cell differentiation.
AB  - Dendritic cells (DCs) are important sentinels within innate immunity, monitoring
      the presence of infectious microorganisms. They operate in 2 different maturation
      stages, with transition from immature to mature DCs being induced by activation
      of toll-like receptors (TLRs). However, TLRs are also expressed on precursor
      cells of DCs. Here we analyzed the effects of TLR stimulation during the process
      of granulocyte-macrophage-colony-stimulating factor (GM-CSF)-mediated in vitro
      generation of immature DCs from precursor cells. We show that TLR triggering
      deviated phenotypic and functional differentiation from CD14+ monocytes to CD1a+
      DCs. Similar results were obtained when differentiation of murine myeloid DCs
      from bone marrow cells was analyzed. The inhibitory effects were independent of
      soluble factors. TLR stimulation in DC precursor cells induced proteins of the
      suppressor of cytokine signaling family (SOCS), which correlated with loss of
      sensitivity to GM-CSF. Overexpression of SOCS-1 abolished GM-CSF signal
      transduction. Moreover, forced SOCS-1 expression in DC precursors mimicked the
      inhibitory effects on DC generation observed for TLR stimulation. The results
      indicate that TLR stimulation during the period of DC generation interferes with
      and deviates DC differentiation and that these effects are mediated particularly
      by SOCS-1.

PMID- 16896157
TI  - Developmental kinetics, turnover, and stimulatory capacity of thymic epithelial
      cells.
AB  - Despite the importance of thymic stromal cells to T-cell development, relatively
      little is known about their biology. Here, we use single-cell analysis of stromal
      cells to analyze extensive changes in the number and composition of thymic stroma
      throughout life, revealing a surprisingly dynamic population. Phenotypic
      progression of thymic epithelial subsets was assessed at high resolution in young
      mice to provide a developmental framework. The cellular and molecular
      requirements of adult epithelium were studied, using various mutant mice to
      demonstrate new cross talk checkpoints dependent on RelB in the cortex and CD40
      in the medulla. With the use of Ki67 and BrdU labeling, the turnover of thymic
      epithelium was found to be rapid, but then diminished on thymic involution. The
      various defects in stromal turnover and composition that accompanied involution
      were rapidly reversed following sex steroid ablation. Unexpectedly, mature
      cortical and medullary epithelium showed a potent capacity to stimulate naive T
      cells, comparable to that of thymic dendritic cells. Overall, these studies show
      that the thymic stroma is a surprisingly dynamic population and may have a more
      direct role in negative selection than previously thought.

PMID- 16896158
TI  - Smad5 is dispensable for adult murine hematopoiesis.
AB  - Smad5 is known to transduce intracellular signals from bone morphogenetic
      proteins (BMPs), which belong to the transforming growth factor-beta (TGF-beta)
      superfamily and are involved in the regulation of hematopoiesis. Recent findings
      suggest that BMP4 stimulates proliferation of human primitive hematopoietic
      progenitors in vitro, while early progenitors from mice deficient in Smad5
      display increased self-renewal capacity in murine embryonic hematopoiesis. Here,
      we evaluate the role of Smad5 in the regulation of hematopoietic stem cell (HSC)
      fate decisions in adult mice by using an inducible MxCre-mediated conditional
      knockout model. Surprisingly, analysis of induced animals revealed unperturbed
      cell numbers and lineage distribution in peripheral blood (PB), bone marrow (BM),
      and the spleen. Furthermore, phenotypic characterization of the stem cell
      compartment revealed normal numbers of primitive lin(-)Sca-1(+)c-Kit(+) (LSK)
      cells in Smad5(-)(/)(-) BM. When transplanted in a competitive fashion into
      lethally irradiated primary and secondary recipients, Smad5-deficient BM cells
      competed normally with wild-type (wt) cells, were able to provide long-term
      reconstitution for the hosts, and displayed normal lineage distribution. Taken
      together, Smad5-deficient HSCs from adult mice show unaltered differentiation,
      proliferation, and repopulating capacity. Therefore, in contrast to its role in
      embryonic hematopoiesis, Smad5 is dispensable for hematopoiesis in the adult
      mouse.

PMID- 16896156
TI  - c-Rel plays a key role in deficient activation of B cells from a non-X-linked
      hyper-IgM patient.
AB  - Our previous results demonstrated that B cells from a patient (pt1) with non-X
      linked hyper-IgM syndrome (HIGM) possess an atypical CD23(lo) phenotype that is
      unaffected by CD40-mediated activation. To investigate the molecular mechanism
      underlying defective CD23 expression in pt1 B cells, we used lymphoblastoid cell
      lines that express LMP1 under the control of a tetracycline-inducible promoter
      (LCL(tet)). Our analysis revealed that the CD23(lo) phenotype in the pt1-LCL(tet)
      cells is a direct consequence of diminished CD23 transcription. We demonstrate a
      marked decrease in c-Rel-containing complexes that bind to the proximal CD23a/b
      promoters in pt1-LCL(tet) extracts, resulting from an overall lower expression of
      c-Rel in pt1-LCL(tet) cells. Analysis of c-Rel mRNA revealed relatively equal
      amounts in pt1-LCL(tet) and control LCL(tet) cells, indicating that diminished c
      Rel protein expression is unrelated to decreased transcription. Finally, a
      critical role for c-Rel in CD23 regulation was demonstrated by effectively
      altering c-Rel expression that resulted in the direct modulation of CD23 surface
      expression. Collectively, these findings demonstrate that low levels of c-Rel are
      the underlying cause of aberrant CD23 expression in pt1 B cells and are likely to
      play a critical role in the pathophysiology of this form of HIGM.

PMID- 16896159
TI  - Immune competence of cancer-reactive T cells generated de novo in adult tumor
      bearing mice.
AB  - The impact of timing of antigen introduction into fetus and neonates leads to the
      suggestion that pre-existing antigens are tolerogenic to immunocompetent cells
      generated thereafter. This hypothesis predicts that in patients with cancer who
      are undergoing bone marrow transplantation, newly produced T cells with
      specificity for pre-existing tumor cells will be inactivated by the tumor
      antigens in the host. Because the effect of tumor cells on developing cancer
      reactive T cells has not been investigated, we set out to systematically analyze
      the impact of tumor cells in the periphery on the development of tumor-reactive T
      cells in the thymus and their immunocompetence in the periphery. Our data
      demonstrate that in the host in which a tumor is established in the periphery,
      the cancer-reactive T cells develop normally, remain fully immunocompetent,
      become activated in the periphery, and cause regression of large established
      tumors. The immunocompetence of T cells generated in an antigen-bearing host is
      also confirmed in a skin graft transplantation model.

PMID- 16896160
TI  - Mechanism for fetal hemoglobin induction by histone deacetylase inhibitors
      involves gamma-globin activation by CREB1 and ATF-2.
AB  - The histone deacetylase inhibitors (HDA-CIs) butyrate and trichostatin A activate
      gamma-globin expression via a p38 mitogen-activating protein kinase (MAPK)
      dependent mechanism. We hypothesized that down-stream effectors of p38 MAPK,
      namely activating transcription factor-2 (ATF-2) and cyclic AMP response element
      (CRE) binding protein (CREB), are intimately involved in fetal hemoglobin
      induction by these agents. In this study, we observed increased ATF-2 and CREB1
      phosphorylation mediated by the HDACIs in K562 cells, in conjunction with histone
      H4 hyperacetylation. Moreover, enhanced DNA-protein interactions occurred in the
      CRE in the (G)gamma-globin promoter (G-CRE) in vitro after drug treatments;
      subsequent chromatin immunoprecipitation assay confirmed ATF-2 and CREB1 binding
      to the G-CRE in vivo. Enforced expression of ATF-2 and CREB produced (G)gamma
      promoter trans-activation which was abolished by a 2-base pair mutation in the
      putative G-CRE. The data presented herein demonstrate that gamma-gene induction
      by butyrate and trichostatin A involves ATF-2 and CREB1 activation via p38 MAPK
      signaling.

PMID- 16896162
TI  - Cellular localization of apelin and its receptor in the anterior pituitary:
      evidence for a direct stimulatory action of apelin on ACTH release.
AB  - Apelin is a bioactive peptide recently identified as the endogenous ligand of the
      human orphan G protein-coupled receptor APJ. The presence of apelin
      immunoreactive nerve fibers, together with the detection of apelin receptor mRNA
      in the parvocellular part of the paraventricular nucleus and the stimulatory
      action of apelin on corticotropin-releasing hormone release, indicate that apelin
      modulates adrenocorticotropin (ACTH) release via an indirect action on the
      hypothalamus. However, a direct action of apelin in the anterior pituitary cannot
      be excluded. Here, we provided evidence for the existence of an apelinergic
      system within the adult male rat pituitary gland. Double immunofluorescence
      staining indicated that apelin is highly coexpressed in the anterior pituitary,
      mainly in corticotrophs (96.5 +/- 0.3%) and to a much lower extent in
      somatotropes (3.2 +/- 0.2%). Using in situ hybridization combined with
      immunohistochemistry, a high expression of apelin receptor mRNA was also found in
      corticotrophs, suggesting a local interaction between apelin and ACTH. In an ex
      vivo perifusion system of anterior pituitaries, apelin 17 (K17F, 10(-6) M)
      significantly increased basal ACTH release by 41%, whereas apelin 10 (R10F, 10(
      6) M), an inactive apelin fragment, was ineffective. In addition, K17F but not
      R10F induced a dose-dependent increase in K(+)-evoked ACTH release, with maximal
      increase being observed for a 10(-6) M concentration. Taken together, these data
      outline the potential role of apelin as an autocrine/paracrine-acting peptide on
      ACTH release and provide morphological and neuroendocrine basis for further
      studies that explore the physiological role of apelin in the regulation of
      anterior pituitary functions.

PMID- 16896161
TI  - Muscle glucose transport and phosphorylation in type 2 diabetic, obese
      nondiabetic, and genetically predisposed individuals.
AB  - Our objectives were to quantitate insulin-stimulated inward glucose transport and
      glucose phosphorylation in forearm muscle in lean and obese nondiabetic subjects,
      in lean and obese type 2 diabetic (T2DM) subjects, and in normal glucose
      tolerant, insulin-resistant offspring of two T2DM parents. Subjects received a
      euglycemic insulin (40 mU.m(-2).min(-1)) clamp with brachial artery/deep forearm
      vein catheterization. After 120 min of hyperinsulinemia, a bolus of d-mannitol/3
      O-methyl-d-[(14)C]glucose/d-[3-(3)H]glucose (triple-tracer technique) was given
      into brachial artery and deep vein samples obtained every 12-30 s for 15 min.
      Insulin-stimulated forearm glucose uptake (FGU) and whole body glucose metabolism
      (M) were reduced by 40-50% in obese nondiabetic, lean T2DM, and obese T2DM
      subjects (all P < 0.01); in offspring, the reduction in FGU and M was
      approximately 30% (P < 0.05). Inward glucose transport and glucose
      phosphorylation were decreased by approximately 40-50% (P < 0.01) in obese
      nondiabetic and T2DM groups and closely paralleled the decrease in FGU. The
      intracellular glucose concentration in the space accessible to glucose was
      significantly greater in obese nondiabetic, lean T2DM, obese T2DM, and offspring
      compared with lean controls. We conclude that 1) obese nondiabetic, lean T2DM,
      and offspring manifest moderate-to-severe muscle insulin resistance (FGU and M)
      and decreased insulin-stimulated glucose transport and glucose phosphorylation in
      forearm muscle; these defects in insulin action are not further reduced by the
      combination of obesity plus T2DM; and 2) the increase in intracelullar glucose
      concentration under hyperinsulinemic euglycemic conditions in obese and T2DM
      groups suggests that the defect in glucose phosphorylation exceeds the defect in
      glucose transport.

PMID- 16896163
TI  - Intracerebral administration of protein kinase A or cAMP response element-binding
      protein antisense oligonucleotide can modulate amphetamine-mediated appetite
      suppression in free-moving rats.
AB  - Although amphetamine (AMPH)-induced appetite suppression has been attributed to
      its inhibitory action on neuropeptide Y (NPY), an appetite neurotransmitter
      abundant in the brain, molecular mechanisms underlying this effect are not well
      known. This study examined the possible role of protein kinase A (PKA) and cAMP
      response element-binding protein (CREB) signaling in this anorectic effect, and
      the results showed that both PKA and CREB mRNA levels in hypothalamus were
      increased following AMPH treatment, which was relevant to a reduction of NPY mRNA
      level. To determine whether PKA or CREB was involved in the anorectic response,
      intracerebroventricular infusions of antisense oligonucleotide (or missense
      control) were performed 60 min before daily AMPH treatment in conscious rats, and
      results showed that either PKA or CREB knockdown could block AMPH-induced
      anorexia as well as restore NPY mRNA level, indicating the respective involvement
      of PKA and CREB signaling in the regulation of NPY gene expression. It is
      suggested that hypothalamic PKA and CREB signaling may involve the central
      regulation of AMPH-mediated feeding suppression via the modulation of NPY gene
      expression.

PMID- 16896164
TI  - Inactivation of PKCtheta leads to increased susceptibility to obesity and dietary
      insulin resistance in mice.
AB  - In this study, we investigated the metabolic phenotype of PKCtheta knockout mice
      (C57BL/6J) on chow diet and high-fat diet (HFD). The knockout (KO) mice are
      normal in growth and reproduction. On the chow diet, body weight and food intake
      were not changed in the KO mice; however, body fat content was increased with a
      corresponding decrease in body lean mass. Energy expenditure and spontaneous
      physical activity were decreased in the KO mice. On HFD, energy expenditure and
      physical activity remained low in the KO mice. The body weight and fat content
      were increased rapidly in the KO mice. At 8 wk on HFD, severe insulin resistance
      was detected in the KO mice with hyperinsulinemic euglycemic clamp and insulin
      tolerance test. Insulin action in both hepatic and peripheral tissues was reduced
      in the KO mice. Plamsa free fatty acid was increased, and expression of
      adiponectin in the adipose tissue was decreased, in the KO mice on HFD. This
      study suggests that loss of PKCtheta reduces energy expenditure and increases the
      risk of dietary obesity and insulin resistance in mice.

PMID- 16896167
TI  - Contributions of working muscle to whole body lipid metabolism are altered by
      exercise intensity and training.
AB  - To evaluate the contribution of working muscle to whole body lipid oxidation, we
      examined the effects of exercise intensity and endurance training (9 wk, 5
      days/wk, 1 h, 75% Vo(2 peak)) on whole body and leg free fatty acid (FFA)
      kinetics in eight male subjects (26 +/- 1 yr, means +/- SE). Two pretraining
      trials [45 and 65% Vo(2 max) (45UT, 65UT)] and two posttraining trials [65% of
      pretraining Vo(2 peak) (ABT), and 65% of posttraining Vo(2 peak) (RLT)] were
      performed using [1-(13)C]palmitate infusion and femoral arteriovenous sampling.
      Training increased Vo(2 peak) by 15% (45.2 +/- 1.2 to 52.0 +/- 1.8 ml.kg(-1).min(
      1), P < 0.05). Muscle FFA fractional extraction was lower during exercise (EX)
      compared with rest regardless of workload or training status ( approximately 20
      vs. 48%, P < 0.05). Two-leg net FFA balance increased from net release at rest (
      approximately -36 micromol/min) to net uptake during EX for 45UT (179 +/- 75),
      ABT (236 +/- 63), and RLT (136 +/- 110) (P < 0.05), but not 65UT (51 +/- 127).
      Leg FFA tracer measured uptake was higher during EX than rest for all trials and
      greater during posttraining in RLT (716 +/- 173 micromol/min) compared with
      pretraining (45UT 450 +/- 80, 65UT 461 +/- 72, P < 0.05). Leg muscle lipid
      oxidation increased with training in ABT (730 +/- 163 micromol/min) vs. 65UT (187
      +/- 94, P < 0.05). Leg muscle lipid oxidation represented approximately 62 and
      30% of whole body lipid oxidation at lower and higher relative intensities,
      respectively. In summary, training can increase working muscle tracer measured
      FFA uptake and lipid oxidation for a given power output, but both before and
      after training the association between whole body and leg lipid metabolism is
      reduced as exercise intensity increases.

PMID- 16896166
TI  - Stimulation of net muscle protein synthesis by whey protein ingestion before and
      after exercise.
AB  - Timing of nutrient ingestion has been demonstrated to influence the anabolic
      response of muscle following exercise. Previously, we demonstrated that net amino
      acid uptake was greater when free essential amino acids plus carbohydrates were
      ingested before resistance exercise rather than following exercise. However, it
      is unclear if ingestion of whole proteins before exercise would stimulate a
      superior response compared with following exercise. This study was designed to
      examine the response of muscle protein balance to ingestion of whey proteins both
      before and following resistance exercise. Healthy volunteers were randomly
      assigned to one of two groups. A solution of whey proteins was consumed either
      immediately before exercise (PRE; n = 8) or immediately following exercise (POST;
      n = 9). Each subject performed 10 sets of 8 repetitions of leg extension
      exercise. Phenylalanine concentrations were measured in femoral arteriovenous
      samples to determine balance across the leg. Arterial amino acid concentrations
      were elevated by approximately 50%, and net amino acid balance switched from
      negative to positive following ingestion of proteins at either time. Amino acid
      uptake was not significantly different between PRE and POST when calculated from
      the beginning of exercise (67 +/- 22 and 27 +/- 10 for PRE and POST,
      respectively) or from the ingestion of each drink (60 +/- 17 and 63 +/- 15 for
      PRE and POST, respectively). Thus the response of net muscle protein balance to
      timing of intact protein ingestion does not respond as does that of the
      combination of free amino acids and carbohydrate.

PMID- 16896168
TI  - Application of the nuclear factor-kappaB inhibitor BAY 11-7085 for the treatment
      of endometriosis: an in vitro study.
AB  - Most of the current medical treatments for endometriosis aim to downregulate
      estrogen activity. However, a high recurrence rate after medical treatment has
      been the most significant problem. BAY 11-7085, a soluble inhibitor of NK-kappaB
      activation, has been shown to inhibit cell proliferation and induce apoptosis of
      a variety of cells. To examine the potential application of BAY 11-7085 in the
      treatment of endometriosis, we investigated the effects of this agent on the cell
      proliferation and apoptosis of cultured ovarian endometriotic cyst stromal cells
      (ECSCs) by a modified methylthiazole tetrazolium assay, a 5-bromo-2'-deoxyuridine
      incorporation assay, and internucleosomal DNA fragmentation assays. The effect of
      BAY 11-7085 on the cell cycle of ECSCs was also determined by flow cytometry. The
      expression of apoptosis-related molecules was examined in ECSCs with Western blot
      analysis. BAY 11-7085 significantly inhibited the cell proliferation and DNA
      synthesis of ECSCs and induced apoptosis and the G0/G1 phase cell cycle arrest of
      these cells. Additionally, downregulation of the B-cell lymphoma/leukemia-2 (Bcl
      2) and Bcl-X(L) expression with simultaneous activation of caspase-3, -8, and -9
      was observed in ECSCs after treatment with BAY 11-7085. These results suggest
      that BAY 11-7085 induces apoptosis of ECSCs by suppressing antiapoptotic
      proteins, and that caspase-3-, -8-, and -9-mediated cascades are involved in this
      mechanism. Therefore, BAY 11-7085 could be used as a therapeutic agent for the
      treatment of endometriosis.

PMID- 16896165
TI  - Basal muscle intracellular amino acid kinetics in women and men.
AB  - Sexual dimorphism in skeletal muscle mass is apparent, with men having more
      muscle mass and larger individual muscle cells. However, no sex-based differences
      have been detected in blood forearm phenylalanine turnover, although whole body
      leucine oxidation has been reported to be greater in men than in women. We
      hypothesized that sex differences in intracellular amino acid turnover may
      account for these discrepancies, with men having a higher intracellular turnover
      than women. We studied young, healthy women (women, n = 8) and men (men, n = 10)
      following an overnight fast. Phenylalanine, leucine, and alanine muscle
      intracellular kinetics were assessed using stable isotope methodologies, femoral
      arteriovenous blood sampling, and muscle biopsies. Muscle intracellular amino
      acid kinetics were reported relative to both leg volume and lean leg mass because
      of sex differences in leg volume and in muscle and fat distribution. When
      expressed per leg volume (nmol.min(-1).100 ml leg volume(-1)), phenylalanine net
      balance (women: -16 +/- 4, men: -31 +/- 5), release from proteolysis in the blood
      (women: 46 +/- 9, men: 75 +/- 10) and intracellular availability (women: 149 +/-
      23, men: 241 +/- 35), and alanine production, utilization, and intracellular
      availability were higher in men (P < 0.05). However, when the kinetic parameters
      were normalized per unit of lean leg mass, all differences disappeared. Muscle
      fractional synthetic rate was also not different between women and men. We
      conclude that there are no sex-based differences in basal muscle intracellular
      amino acid turnover when the data are normalized by lean mass. It remains to be
      determined if there are sex differences in intracellular amino acid metabolism
      following anabolic or catabolic stimuli.

PMID- 16896169
TI  - Influences of calorie restriction and age on energy expenditure in the rhesus
      monkey.
AB  - Caloric restriction (CR) is known to retard the aging process, and a marker of
      aging is decreased energy expenditure (EE). To assess longitudinal effects of CR
      on EE in rhesus monkeys (Macaca mulatta), data from 41 males (M) and 26 females
      (F) subjected to 9 or 15 yr of CR were studied. EE and body composition of
      monkeys 11-28 yr of age were measured using indirect calorimetry and dual X-ray
      absorptiometry. Total EE (24-h EE) was divided into daytime (day EE), nighttime
      (night EE), and daytime minus nighttime (D - N EE). M calorie-restricted monkeys
      showed a lower 24-h EE (means +/- SD = 568 +/- 96 kcal/day, P < 0.0001) than
      controls (C; 630 +/- 129 kcal/day). Calorie-restricted M had a lower night EE
      (difference = 36 kcal P < 0.0001) compared with C M, but after adjusting for FFM
      and FM, night EE was not different between calorie-restricted and C males (P =
      0.72). The 24-h EE decreased with age (13 kcal decrease/yr, P < 0.0001), but
      there was no difference between CR and C. Adjusted for FFM and FM, D - N EE
      decreased with age (9 kcal/yr, P < 0.0001), with no interaction with age (P =
      0.72). The F were compared with age-matched M selected from the male cohort. F
      had a lower 24-h EE (496 +/- 84 kcal/day) than M (636 +/- 139 kcal/day) (P <
      0.0001). Adjusting for FFM and FM, night EE was lower in F compared with M
      (difference = 18 kcal, P = 0.077). Night EE did not differ between calorie
      restricted and C younger monkeys after adjusting for FFM and FM. In conclusion,
      CR did not alter the age-related decrease in EE with CR.

PMID- 16896172
TI  - Speech characteristics of patients with pallido-ponto-nigral degeneration and
      their application to presymptomatic detection in at-risk relatives.
AB  - PURPOSE: This report describes the speech characteristics of individuals with a
      neurodegenerative syndrome called pallido-ponto-nigral degeneration (PPND) and
      examines the speech samples of at-risk, but asymptomatic, relatives for possible
      preclinical detection. METHOD: Speech samples of 9 members of a PPND kindred were
      subjected to perceptual characterization. Speech deterioration patterns were
      reported for 2 participants followed longitudinally at 6-month intervals. Cross
      sectional findings were reported for 3 participants at various stages of disease.
      Longitudinal and cross-sectional findings were used to guide the examination of 4
      at-risk, but asymptomatic, participants. RESULTS: Results revealed a progressive
      mixed dysarthria with hypokinetic, spastic, and flaccid features. It was
      characterized primarily by vocal tremor and high-frequency vocal flutter,
      speaking rate abnormalities most often in the direction of slowing, and a
      tendency toward monopitch. Dysarthria progression was marked by exacerbation and
      increasing severity of early features, progressive decrease in spontaneous speech
      output, verbal perseverations, and eventual mutism. Results for at-risk
      participants revealed preclinical speech abnormalities that preceded other motor
      signs. Speech results were examined in light of available autopsy findings for
      site of lesion associations. CONCLUSION: The dysarthria of PPND is an early
      harbinger of disease onset. It has a mixed presentation, with hypokinetic,
      spastic, and flaccid features.

PMID- 16896171
TI  - Facilitating behavioral change in voice therapy: the relevance of motivational
      interviewing.
AB  - PURPOSE: The purpose of this article is to present an exploration of some of the
      issues surrounding adherence to vocal behavioral change in voice therapy within
      the context of Motivational Interviewing (MI) and to explore MI's potential for
      integration into voice therapy (MI-adapted voice therapy). MI is a style of
      interpersonal communication in which resistance is minimized through the use of
      skillful listening in a directive, constructive discussion about behavior change.
      The goal of MI-adapted voice therapy is to enhance patient adherence to vocal
      behavioral change. METHOD: A narrative review of the literature is presented,
      together with the experiences of the author with 10 adult patients with voice
      disorders who participated in MI-adapted voice therapy. RESULTS: It is shown that
      the principles of MI can be applied throughout the therapy program. Points of
      resistance to vocal behavioral change that were common across many patients
      appeared to be addressed appropriately by specific MI dialogue strategies.
      CONCLUSIONS: It is concluded that MI-adapted voice therapy holds promise as an
      approach to address patient adherence to vocal behavioral change. However,
      research is necessary to define the efficacy of this approach and the factors
      associated with its efficacy.

PMID- 16896174
TI  - The composition of normative groups and diagnostic decision making: shooting
      ourselves in the foot.
AB  - PURPOSE: The normative group of a norm-referenced test is intended to provide a
      basis for interpreting test scores. However, the composition of the normative
      group may facilitate or impede different types of diagnostic interpretations.
      This article considers who should be included in a normative sample and how this
      decision must be made relative to the purpose for which a test is intended.
      METHOD: The way in which the composition of the normative sample affects
      classification accuracy is demonstrated through a test review followed by a
      simulation study. The test review examined the descriptions of the normative
      group in a sample of 32 child language tests. The mean performance reported in
      the test manual for the sample of language impaired children was compared with
      the sample's norms, which either included or excluded children with language
      impairment. For the simulation, 2 contrasting normative procedures were modeled.
      The first procedure included a mixed group of representative cases (language
      impaired and normal cases). The second procedure excluded the language impaired
      cases from the norm. RESULTS: Both the data obtained from test manuals and the
      data simulation based on population characteristics supported our claim that use
      of mixed normative groups decreases the ability to accurately identify language
      impairment. Tests that used mixed norms had smaller differences between the
      normative and language impaired groups in comparison with tests that excluded
      children with impairment within the normative sample. The simulation demonstrated
      mixed norms that lowered the group mean and increased the standard deviation,
      resulting in decreased classification accuracy. CONCLUSIONS: When the purpose of
      testing is to identify children with impaired language skills, including children
      with language impairment in the normative sample can reduce identification
      accuracy.

PMID- 16896173
TI  - Comparison of meaning and graphophonemic feedback strategies for guided reading
      instruction of children with language delays.
AB  - PURPOSE: Guided reading is a common practice recommended for children in the
      early stages of literacy development. While experts agree that oral reading
      facilitates literacy skills, controversy exists concerning which corrective
      feedback strategies are most effective. The purpose of this study was to compare
      feedback procedures stemming from 2 different theoretical perspectives on
      literacy development. METHOD: Fourteen children with specific language impairment
      (SLI) and 21 with typically developing language read aloud 2 stories to an adult
      examiner who presented corrective feedback prompts when reading miscues (errors)
      occurred. One type of feedback based on whole language principles emphasized
      meaning aspects of a text. The other type consisted of graphophonemic (GP) word
      decoding strategies. Before reading, participants were provided instruction on 5
      key words taken from each story text. This instruction emphasized either meaning
      or GP aspects of specific key words. Story comprehension questions followed
      readings. RESULTS: Findings indicated that more miscued words were corrected
      overall through the use of GP feedback cues; however, some meaning-based
      instructional advantages were indicated for key word identifications for children
      with SLI. Higher story comprehension scores were yielded in the GP condition for
      both groups. CONCLUSIONS: Both meaning-based and phonemic key word reviews, prior
      to oral reading, appear to be effective strategies for children with SLI. The use
      of GP word-decoding cues may be more effective than meaning-based cues for
      facilitating correction of reading miscues during children's oral readings.
      Further research findings are discussed along with clinical implications for
      using corrective feedback procedures.

PMID- 16896175
TI  - Clinical relevance of discourse characteristics after right hemisphere brain
      damage.
AB  - PURPOSE: Discourse characteristics of adults with right hemisphere brain damage
      are similar to those reported for healthy older adults, prompting the question of
      whether changes are due to neurological lesions or normal aging processes. The
      clinical relevance of potential differences across groups was examined through
      ratings by speech-language pathologists. METHOD: A thinking-out-loud task was
      used to elicit discourse from 8 individuals with right brain damage and 8 healthy
      older adults. Speech-language pathologists rated discourse transcripts on content
      and quantity variables and then classified them as belonging to a participant
      with or without brain damage. Subjective ratings were validated against
      corroborating measures. RESULTS: Discourse produced by adults with right brain
      damage was rated as more tangential and egocentric than that from healthy older
      adults. Extreme verbosity or paucity of speech was attributed to people with
      right brain damage. One third of the speech-language pathologists accurately
      classified discourse samples according to group, whereas the others displayed
      biases toward one group or the other. CONCLUSIONS: Tangentiality, egocentrism,
      and extremes of quantity are clinically relevant characteristics of discourse
      produced by adults with right brain damage. Speech-language pathologists must be
      aware of potential biases that influence their perception of "normal" discourse
      production.

PMID- 16896176
TI  - A closer look at transcription intelligibility for speakers with dysarthria:
      evaluation of scoring paradigms and linguistic errors made by listeners.
AB  - PURPOSE: This study addressed the effects of 3 different paradigms for scoring
      orthographic transcriptions of dysarthric speech on intelligibility scores. The
      study also examined whether there were differences in transcription accuracy
      among words from different linguistic classes. METHOD: Speech samples were
      collected from 12 speakers with dysarthria of varying severity. Twelve different
      listeners made orthographic transcriptions of each speaker, for a total of 144
      listeners. Transcriptions were scored using 3 different paradigms: total word
      phonemic match, informational word phonemic match, and informational word
      semantic match. Transcriptions were also coded into 3 linguistic categories:
      content words, modifiers, and functors. The number of words that each listener
      transcribed correctly within each category was tallied. RESULTS: There were
      significant differences among the 3 scoring paradigms. However, the magnitude of
      differences was relatively small. In addition, listeners transcribed functor
      words more accurately than content words or modifiers. They also transcribed free
      morphemes more accurately than bound morphemes. CONCLUSIONS: The specific scoring
      paradigm that clinicians employ for measuring speech intelligibility appears to
      be relatively inconsequential as long as consistent procedures are used. Analyses
      of the kinds of words that listeners transcribe correctly suggest that
      interventions focusing on listener processing strategies should be considered for
      enhancing intelligibility of speakers with chronic dysarthria.

PMID- 16896177
TI  - Comparison of context-based interaction patterns of mothers who are homeless with
      their preschool children.
AB  - PURPOSE: The primary purpose of this exploratory study was to examine the
      influence of context on interaction patterns used by mothers who are homeless
      with their preschool children during book-reading and game-playing activities.
      The impact of mothers' previously determined language functioning on their
      contextual use of facilitating language utterances was also examined. METHOD:
      Using a prospective, nonrandomized, comparison group design, mothers read a book
      and played a game with their preschool children. Facilitating language utterances
      produced by the mothers in 16 mother-child dyads during each activity were
      analyzed. RESULTS: Regardless of their language functioning, no significant
      contextual differences in percentage use of facilitating language utterances were
      found across mothers. Overall maternal use of facilitating utterances was less
      than 50%. Across both contexts, mothers used few different types of facilitating
      language utterances. CONCLUSIONS: This exploratory study provides initial
      evidence of overall consistency of facilitating language utterance use by mothers
      who are homeless during interactions with their preschool children across
      contexts, regardless of maternal language functioning. This study provides an
      initial framework for future research investigating the interactions of families
      who are homeless and discusses possible language interventions for these at-risk
      families.

PMID- 16896178
TI  - Reduced speaking rate as an early predictor of reading disability.
AB  - PURPOSE: This study evaluated whether developmental reading disability could be
      predicted in children at the age of 30 months, according to 3 measures of speech
      production: speaking rate, articulation rate, and the proportion of speaking time
      allocated to pausing. METHOD: Speech samples of 18 children at high risk and 10
      children at low risk for reading disability were recorded at 30 months of age.
      High risk was determined by history of reading disability in at least 1 of the
      child's parents. In grade school, a reading evaluation identified 9 children
      within the high-risk group as having reading disability and 9 children as not
      having reading disability. The 10 children at low risk for reading disability
      tested negative for reading disability. RESULTS: Children with reading disability
      showed a significantly slower speaking rate than children at high risk without
      reading disability. Children with reading disability allocated significantly more
      time to pausing, as compared with the other groups. Articulation rate did not
      differ significantly across groups. CONCLUSIONS: Speaking rate and the proportion
      of pausing time to speaking time may provide an early indication of reading
      outcome in children at high risk for reading disability.

PMID- 16896179
TI  - Proteomic analysis of the adaptive response of rat renal proximal tubules to
      metabolic acidosis.
AB  - Proximal tubules were isolated from control and acidotic rats by collagenase
      digestion and Percoll density gradient centrifugation. Western blot analysis
      indicated that the tubules were approximately 95% pure. The samples were analyzed
      by two-dimensional difference gel electrophoresis (DIGE) and DeCyder software was
      used to quantify the temporal changes in proteins that exhibit enhanced or
      reduced expression. The mass-to-charge ratios and the amino acid sequences of the
      recovered tryptic peptides were determined by MALDI-TOF/TOF mass spectrometry and
      the proteins were identified using Mascot software. This analysis confirmed the
      well-characterized adaptive responses in glutaminase (GA), glutamate
      dehydrogenase (GDH), and phosphoenolpyruvate carboxykinase (PEPCK). This approach
      also identified 17 previously unrecognized proteins that are increased with
      ratios of 1.5 to 5.6 and 16 proteins that are decreased with ratios of 0.67 to
      0.03 when tubules from 7-day acidotic vs. control rats were compared. Some of
      these changes were confirmed by Western blot analysis. Temporal studies
      identified proteins that were induced either with rapid kinetics similar to PEPCK
      or with more gradual profiles similar to GA and GDH. All of the mRNAs that encode
      the latter proteins contain an AU sequence that is homologous to the pH response
      element found in GA mRNA. Thus selective mRNA stabilization may be a predominant
      mechanism by which protein expression is increased in response to acidosis.

PMID- 16896181
TI  - Novel mouse strain with Cre recombinase in 11beta-hydroxysteroid dehydrogenase-2
      expressing cells.
AB  - Here we describe the generation and characterization of a mouse strain that
      expresses an improved Cre (iCre) recombinase (48) under the control of the
      endogenous 11beta-hydroxysteroid dehydrogenase type 2 (11HSD2) promoter. Progeny
      of 11HSD2/iCre and ROSA26 reporter mice were used to determine the pattern of
      iCre expression by measuring the activity of the LacZ gene product beta
      galactosidase in a panel of tissues. On Cre recombinase activity, intense beta
      galactosidase activity (X-gal staining) was observed in the classic
      mineralocorticoid target segments of the kidney, as well as in the colon, and
      both female and male reproductive organs. Weaker iCre expression was detected in
      the lung and heart. In the brain, strong iCre activity was present in
      cardiovascular centers that are known to express 11HSD2 and mineralocorticoid
      receptors [nucleus tractus solitarius (NTS) and amygdala] as well as in the
      granular layer of the cerebellum. iCre expression was weaker in neonatal kidney
      and colon than in the adult but was present in the hair follicles and cartilage.
      These results indicate that in the 11HSD2/iCre strain iCre expression faithfully
      represents the expression pattern of endogenous 11HSD2. Thus this mouse model
      represents the first Cre deleter strain that can be used to eliminate desired
      genes in every mineralocorticoid target tissue. This mouse model should serve as
      a useful resource for investigators who want to study the function of genes
      involved in aldosterone action and genes in other pathways that are selectively
      expressed in these cells.

PMID- 16896180
TI  - Glibenclamide prevents increased extracellular matrix formation induced by high
      glucose concentration in mesangial cells.
AB  - Other than stimulation of cell contractility, little is known about the potential
      metabolic effects induced by sulfonylureas, independently of insulin action.
      Previous studies from our laboratory demonstrated complete abrogation of
      glomerulosclerosis in an experimental model of type 1 diabetes chronically (9 mo)
      treated with low-dose sulfonylureas (Biederman JI, Vera E, Pankhaniya R, Hassett
      C, Giannico G, Yee J, Cortes P. Kidney Int 67: 554-565, 2005). Therefore, the
      effects of glibenclamide (Glib) on net collagen I, collagen IV, and fibronectin
      medium net secretion and cell layer collagen I deposition were investigated in
      mesangial cells continuously exposed to 25 mM glucose for 8 wk and treated with
      predetermined increasing concentrations of Glib for the same period. Clinically
      relevant concentrations (0.01 microM) of Glib fully suppressed the high glucose
      enhanced accumulation of collagen I, collagen IV, and fibronectin in the medium
      and inhibited collagen I deposition in the cell layer. These effects occurred
      while transforming growth factor (TGF)-beta1 medium concentration remained
      elevated and glucose uptake was increased to levels above those in 25 mM glucose
      incubated cultures. The decreased collagen I accumulation occurred simultaneously
      with enhanced collagen I mRNA expression in concert with marked suppression of
      plasminogen inhibitor type-1 (PAI-1) mRNA and protein expression. This strongly
      suggests an accelerated matrix turnover favoring breakdown. Glib-induced effects
      demonstrated a biphasic pattern, being absent or reversed in cells treated with
      higher Glib concentrations (0.1 or 1 microM). Therefore, chronic Glib treatment
      at low concentrations markedly diminishes the high glucose-induced enhanced
      accumulation of extracellular matrix components by suppression of steady-state
      PAI-1 transcriptional activity. These results and those previously reported in
      vivo suggest that long-term Glib treatment may prevent glomerulosclerosis in
      insulin-deficient diabetes.

PMID- 16896182
TI  - Chronic inhibition of nuclear factor-kappaB attenuates renal injury in the 5/6
      renal ablation model.
AB  - Recent studies indicated that the nuclear transcription factor, NF-kappaB,
      activates a number of proinflammatory genes in subjects with progressive
      nephropathies. We investigated whether NF-kappaB inhibition limits progressive
      renal injury in the 5/6 renal ablation model (Nx). Adult male Munich-Wistar rats
      were subdivided in four groups: S (n = 16), subjected to sham operation; S+PDTC
      (n = 18), sham-operated rats receiving the NF-kappaB inhibitor pyrrolidine
      dithiocarbamate (PDTC; 60 mg x kg(-1) x day(-1)) in drinking water; Nx (n = 16),
      Nx rats receiving vehicle only; and Nx+PDTC (n = 19), Nx rats given PDTC as
      above. Thirty days after renal ablation, Nx rats exhibited systemic and
      glomerular hypertension. Only the former was attenuated by PDTC treatment. Sixty
      days after renal ablation, Nx rats exhibited marked hypertension, albuminuria and
      creatinine retention, as well as glomerulosclerosis and cortical interstitial
      expansion/inflammation. Immunohistochemical analysis of Nx rats showed renal
      interstitial infiltration by macrophages and by cells staining positively for ANG
      II and its receptor, AT(1). Glomerular and interstitial cells expressing the p65
      subunit of the NF-kappaB system were also found. PDTC treatment attenuated renal
      injury and inflammation, as well as the density of cells staining positively for
      the p65 subunit. Activation of the NF-kappaB system plays an important role in
      the pathogenesis of renal injury in the Nx model. Inhibition of this system may
      represent a new strategy to prevent the progression of chronic kidney disease.

PMID- 16896183
TI  - Induction of kidney injury molecule-1 in homozygous Ren2 rats is attenuated by
      blockade of the renin-angiotensin system or p38 MAP kinase.
AB  - Kidney injury molecule-1 (Kim-1) is associated with ischemic and proteinuric
      tubular injury; however, whether dysregulation of the renin-angiotensin system
      (RAS) can also induce Kim-1 is unknown. We studied Kim-1 expression in homozygous
      Ren2 rats, characterized by renal damage through excessive RAS activation. We
      also investigated whether antifibrotic treatment (RAS blockade or p38 MAP kinase
      inhibition) would affect Kim-1 expression. At 7 wk of age, homozygous Ren2 rats
      received a nonhypotensive dose of candesartan (0.05 mg x kg(-1) x day(-1) sc) or
      the p38 inhibitor SB-239063 (15 mg x kg(-1) x day(-1) sc) for 4 wk; untreated
      Ren2 and Sprague-Dawley (SD) rats served as controls. Kim-1 mRNA and protein
      expression were determined by quantitative PCR and immunohistochemistry,
      respectively, and related to markers of prefibrotic renal damage. Urinary Kim-1
      was measured in 8-wk-old Ren2 and SD rats with and without angiotensin-converting
      enzyme inhibition (ramipril, 1 mg x kg(-1) x day(-1) in drinking water for 4 wk).
      Untreated Ren2 rats showed a >20-fold increase in renal Kim-1 mRNA (expressed as
      Kim-1-to-GAPDH ratio): 75.5 +/- 43.6 vs. 3.1 +/- 1.0 in SD rats (P < 0.01).
      Candesartan and SB-239063 strongly reduced Kim-1 mRNA: 3.1 +/- 1.5 (P < 0.01) and
      9.8 +/- 4.2 (P < 0.05), respectively. Kim-1 protein expression in damaged tubules
      paralleled mRNA expression. Kim-1 expression correlated with renal osteopontin,
      alpha-smooth muscle actin, and collagen III expression and with
      tubulointerstitial fibrosis. Damaged tubular segments expressing activated p38
      also expressed Kim-1. Urinary Kim-1 was increased in Ren2 vs. SD (458 +/- 70 vs.
      27 +/- 2 pg/ml, P < 0.01) rats and abolished in Ren2 rats treated with ramipril
      (33 +/- 5 pg/ml, P < 0.01). Kim-1 is associated with development of RAS-mediated
      renal damage. Antifibrotic treatment through RAS blockade or p38 MAP kinase
      inhibition reduced Kim-1 in the homozygous Ren2 model.

PMID- 16896184
TI  - DOCA/NaCl-induced chronic kidney disease: a comparison of renal nitric oxide
      production in resistant and susceptible rat strains.
AB  - Recent studies show nitric oxide (NO) deficiency is both a cause and consequence
      of chronic kidney disease (CKD). Reduced renal neuronal NO synthase (nNOS)
      abundance and activity parallel development of CKD with different models in the
      Sprague-Dawley (SD) rats, whereas Wistar Furth (WF) rats are protected against
      CKD and show preserved renal NO production. In this study, we compared renal NO
      in response to DOCA/salt-induced injury between the WF and SD. Studies were
      conducted on sham WF (n = 6) and SD (n = 6) and uninephrectized (UNX)+75 mg
      DOCA+1% NaCl (WF n = 9; SD n = 10) rats followed for 5 wk. Kidneys were harvested
      for Western blot, NOS activity, and histology. Other measurements included
      creatinine clearance and 24-h total NO production and urinary protein excretion.
      Absolute values of kidney weight were lower in WF than SD rats that showed
      similar percent increases with UNX+DOCA/NaCl. Proteinuria and decreased
      creatinine clearance were present in the SD but not the WF rats following
      UNX+DOCA/NaCl. Glomerular injury was mild in the WF compared with SD rats that
      showed many globally damaged glomeruli. Although renal nNOS abundance was
      decreased in both strains (higher baseline in WF), soluble NOS activity was
      maintained in the WF but significantly reduced in the SD rats. Renal endothelial
      NOS abundance and membrane NOS activity were unaffected by treatment. In summary,
      WF rats showed resistance to UNX+DOCA/NaCl-induced CKD with maintained renal NO
      production despite mild reduction in nNOS abundance. Further studies are needed
      to evaluate how WF rats maintain renal NO production despite similar changes in
      abundance as the vulnerable SD strain.

PMID- 16896185
TI  - Angiotensin metabolism in renal proximal tubules, urine, and serum of sheep:
      evidence for ACE2-dependent processing of angiotensin II.
AB  - Despite the evidence that angiotensin-converting enzyme (ACE)2 is a component of
      the renin-angiotensin system (RAS), the influence of ACE2 on angiotensin
      metabolism within the kidney is not well known, particularly in experimental
      models other than rats or mice. Therefore, we investigated the metabolism of the
      angiotensins in isolated proximal tubules, urine, and serum from sheep.
      Radiolabeled [(125)I]ANG I was hydrolyzed primarily to ANG II and ANG-(1-7) by
      ACE and neprilysin, respectively, in sheep proximal tubules. The ACE2 product ANG
      (1-9) from ANG I was not detected in the absence or presence of ACE and
      neprilysin inhibition. In contrast, the proximal tubules contained robust ACE2
      activity that converted ANG II to ANG-(1-7). Immunoblots utilizing an NH(2)
      terminal-directed ACE2 antibody revealed a single 120-kDa band in proximal tubule
      membranes. ANG-(1-7) was not a stable product in the tubule preparation and was
      rapidly hydrolyzed to ANG-(1-5) and ANG-(1-4) by ACE and neprilysin,
      respectively. Comparison of activities in the proximal tubules with nonsaturating
      concentrations of substrate revealed equivalent activities for ACE (ANG I to ANG
      II: 248 +/- 17 fmol x mg(-1) x min(-1)) and ACE2 [ANG II to ANG-(1-7): 253 +/- 11
      fmol x mg(-1) x min(-1)], but lower neprilysin activity [ANG II to ANG-(1-4): 119
      +/- 24 fmol x mg(-1) x min(-1); P < 0.05 vs. ACE or ACE2]. Urinary metabolism of
      ANG I and ANG II was similar to the proximal tubules; soluble ACE2 activity was
      also detectable in sheep serum. In conclusion, sheep tissues contain abundant
      ACE2 activity that converts ANG II to ANG-(1-7) but does not participate in the
      processing of ANG I into ANG-(1-9).

PMID- 16896187
TI  - Rapamycin at subimmunosuppressive levels inhibits mesangial cell proliferation
      and extracellular matrix production.
AB  - In view of its proven antiproliferative effects, rapamycin offers potential in
      the treatment of mesangioproliferative disease. Previous data have shown an
      effect of rapamycin on mesangial cell proliferation at high doses and have not
      explored the mechanism of action. Therefore, we explored the effects and
      mechanism of action of low levels of rapamycin on mesangial cell proliferation.
      Primary cultures of mouse mesangial cells were grown in medium containing serum
      with differing concentrations of rapamycin. A rapamycin concentration of 0.1
      ng/ml caused a decrease in cell number and DNA synthesis with no effect on
      apoptosis. Type IV collagen protein production was inhibited at 0.01 ng/ml
      rapamycin, although gene expression was unaffected. P70S6K phosphorylation was
      inhibited in parallel with the effects on cell number and DNA synthesis in a dose
      dependent manner, but no effect was seen at 0.01 ng/ml rapamycin. These data show
      an effect on mesangial cell proliferation and p70S6 kinase phosphorylation of 0.1
      ng/ml rapamycin and an effect on collagen IV production of 0.01 ng/ml rapamycin.
      We suggest that further in vivo studies should explore the potential for low-dose
      rapamycin in the treatment of mesangioproliferative glomerulonephritis.

PMID- 16896186
TI  - Prostaglandin D2 inhibits TGF-beta1-induced epithelial-to-mesenchymal transition
      in MDCK cells.
AB  - In a separate study, we identified PGE2 as a potent inhibitor of TGF-beta1induced
      epithelial-mesenchymal transition (EMT) in cultured Madin-Darby canine kidney
      (MDCK) cells (Zhang A, Wang M-H, Dong Z, and Yang T. Am J Physiol Renal Physiol
      291: F1323-F1331, 2006). This finding prompted us to examine the roles of other
      prostanoids: PGD2, PGF(2alpha), PGI2, and thromboxane A2 (TXA2). Treatment with
      10 ng/ml TGF-beta1 for 3 days induced EMT as reflected by conversion to the
      spindle-like morphology, loss of E-cadherin, and activation of alpha-smooth
      muscle actin (alpha-SMA). Treatment with PGD2 remarkably preserved the epithelial
      like morphology, restored the expression of E-cadherin, and abolished the
      activation of alpha-SMA. In contrast, PGF(2alpha), carbocyclic thromboxane A2,
      PGI2 and its stable analog beraprost were without an effect. MDCK cells expressed
      DP1 and DP2 receptors; however, the effect of PGD2 was neither prevented by DP1
      antagonist BW-A868C or DP2 antagonist BAY-u3405 nor was mimicked by DP1 agonist
      BW-245C. cAMP-elevating agents forskolin and 8-Br-cAMP blocked EMT. However, cAMP
      blockers H89 and Rp-cAMP failed to block the effect of PGD2. PGD2 did not seem to
      act via its metabolites as 15-deoxy-Delta(12,14)-prostaglandin J2 (15d-PGJ2)
      levels in the medium following incubation with 3 microM PGD2 were well below the
      values predicted from the cross activity of the assay. Exposure to TGF-beta1
      induced a threefold increase in reactive oxygen species production that was
      completely abolished by PGD2. We conclude that 1) PGD2, but not PGI2,
      PGF(2alpha), and TXA2 inhibit EMT, 2) PGD2 inhibits EMT independently of DP1 and
      DP2 receptors, and 3) PGD2 exhibits antioxidant property which may, in part,
      account for the antifibrotic action of this PG.

PMID- 16896188
TI  - Increased AQP2 targeting in primary cultured IMCD cells in response to
      angiotensin II through AT1 receptor.
AB  - Vasopressin and angiotensin II (ANG II) play a major role in renal water and
      Na(+) reabsorption. We previously demonstrated that ANG II AT(1) receptor
      blockade decreases dDAVP-induced water reabsorption and AQP2 levels in rats,
      suggesting cross talk between these two peptide hormones (Am J Physiol Renal
      Physiol 288: F673-F684, 2005). To directly address this issue, primary cultured
      inner medullary collecting duct (IMCD) cells from male Sprague-Dawley rats were
      treated for 15 min with 1) vehicle, 2) ANG II, 3) ANG II + the AT(1) receptor
      blocker candesartan, 4) dDAVP, 5) ANG II + dDAVP, or 6) ANG II + dDAVP +
      candesartan. Immunofluorescence microscopy revealed that 10(-8) M ANG II or 10(
      11) M dDAVP (protocol 1) was associated with increased AQP2 labeling of the
      plasma membrane and decreased cytoplasmic labeling, respectively. cAMP levels
      increased significantly in response to 10(-8) M ANG II and were potentiated by
      cotreatment with 10(-11) M dDAVP. Consistent with this finding, immunoblotting
      revealed that this cotreatment significantly increased expression of
      phosphorylated AQP2. ANG II-induced AQP2 targeting was blocked by 10(-5) M
      candesartan. In protocol 2, treatment with a lower concentration of dDAVP (10(
      12) M) or ANG II (10(-9) M) did not change subcellular AQP2 distribution, whereas
      10(-12) M dDAVP + 10(-9) M ANG II enhanced AQP2 targeting. This effect was
      inhibited by cotreatment with 10(-5) M candesartan. ANG II-induced cAMP
      accumulation and AQP2 targeting were inhibited by inhibition of PKC activity. In
      conclusion, ANG II plays a role in the regulation of AQP2 targeting to the plasma
      membrane in IMCD cells through AT(1) receptor activation and potentiates the
      effect of dDAVP on AQP2 plasma membrane targeting.

PMID- 16896189
TI  - Cellular distribution of the potassium channel KCNQ1 in normal mouse kidney.
AB  - Mechanisms of K(+) secretion and absorption along the collecting duct are not
      understood fully. Because KCNQ1 participates in K(+) secretion within the inner
      ear and stomach, distribution of KCNQ1 in mouse kidney was studied using Northern
      and Western analyses, RT-PCR of isolated tubules, and immunohistochemistry.
      Northern blots demonstrated KCNQ1 transcripts in whole kidney. RT-PCR showed
      KCNQ1 mRNA in isolated distal convoluted tubule (DCT), connecting segment (CNT),
      collecting ducts (CD), and glomeruli. Immunoblots of kidney and stomach revealed
      a approximately 75-kDa protein, the expected mobility for KCNQ1. KCNQ1 was
      detected by immunohistochemistry throughout the distal nephron and CD. Thick
      ascending limbs exhibited weak basolateral immunolabel. In DCT and CNT cells,
      immunolabel was intense and basolateral, although KCNQ1 label was stronger in
      late than in early DCT. Initial collecting tubule and cortical CD KCNQ1
      immunolabel was predominantly diffuse, but many cells exhibited discrete apical
      label. Double-labeling experiments demonstrated that principal cells, type B
      intercalated cells, and a few type A intercalated cells exhibited distinct apical
      KCNQ1 immunolabel. In inner medullary CD, principal cells exhibited distinct
      basolateral KCNQ1 immunolabel, whereas intercalated cells showed diffuse
      cytoplasmic staining. Thus KCNQ1 protein is widely distributed in mouse distal
      nephron and CD, with significant axial and cellular heterogeneity in location and
      intensity. These findings suggest that KCNQ1 has cell-specific roles in renal ion
      transport and may participate in K(+) secretion and/or absorption along the thick
      ascending limb, DCT, connecting tubule, and CD.

PMID- 16896190
TI  - Par-4 is a novel mediator of renal tubule cell death in models of ischemia
      reperfusion injury.
AB  - Prostate apoptosis response-4 (Par-4) is a leucine zipper protein linked to
      apoptotic cell death in prostate cancer and neuronal tissues. The leucine zipper
      domain of Par-4 (Leu.zip) mediates protein-protein interactions that are
      essential for sensitization of cells to apoptosis, and overexpression of Leu.zip
      blocks Par-4 activity in a dominant negative fashion. Ischemia-reperfusion
      induced renal injury (IRI) is clinically important because it typically damages
      renal tubular epithelial cells and glomerular cells, and it is the most common
      cause of acute renal failure (ARF). We now report that Par-4 is expressed in
      renal tubule cells and that aberrant expression of Par-4 activity plays a crucial
      role in activating apoptotic pathways in well-characterized models of renal IRI.
      Increased levels of Par-4 were observed following chemical ischemia-reperfusion
      in HK-2 cells in vitro and in mouse renal tubular cells following bilateral
      clamping of renal pedicles in vivo. Inhibition of Par-4 expression by specific
      par-4 antisense oligonucleotides largely prevented HK-2 cell apoptosis induced by
      IRI. Overexpression of Par-4 in these cells exacerbated mitochondrial dysfunction
      and caspase activation and conferred increased sensitivity to IRI-induced
      apoptosis. Expression of Leu.zip, a dominant negative regulator of Par-4, largely
      prevented mitochondrial dysfunction and caspase activation and significantly
      inhibited IRI-induced apoptosis in HK-2 cells. In addition, transfection of Par-4
      increased while transfection of Leu.zip decreased necrosis in HK-2 cells
      following prolonged IRI. These results identify Par-4 as a novel and early
      mediator of renal tubule cell injury following IRI and provide a potential target
      for developing new therapeutic strategies for renal IRI and ARF.

PMID- 16896192
TI  - Transducing the signals: a G protein takes a new identity.
AB  - The prevailing dogma is that heterotrimeric G proteins exclusively transduce
      signals from the seven-transmembrane motif-containing cell surface receptors,
      also known as G protein-coupled receptors (GPCRs). New evidence indicates that
      Galpha(13), the alpha subunit of the G protein G(13), breaks away from this
      traditional exclusive signaling alliance with GPCRs to transmit signals from
      receptor tyrosine kinases (RTKs), such as platelet-derived growth factor receptor
      (PDGFR), epidermal growth factor receptor (EGFR), and vascular endothelial growth
      factor receptor (VEGFR). Galpha(13) is involved in cell migration in response to
      GPCRs activated by lysophosphatidic acid (LPA) or thrombin. A new report
      indicates that Galpha(13) is also required for cell migration induced by the
      growth factors, such as PDGF, EGF, or VEGF. GPCR coupling is not required for
      such RTK-to-Galpha(13) signaling. This new identity for Galpha(13) as a signal
      transducer for both GPCRs and RTKs may be a forerunner for similar findings
      involving other Galpha subunits. This expanding role of G proteins in both GPCR
      signaling and RTK signaling is likely to have a great impact not only on our
      understanding of cell signaling in general, but also more specifically where the
      dysregulation of signaling by GPCRs, RTKs, and G proteins cause
      pathophysiological changes such as in the case of tumorigenesis, tumor
      progression and/or metastasis.

PMID- 16896191
TI  - Differential regulation of B/K protein expression in proximal and distal tubules
      of rat kidneys with ischemia-reperfusion injury.
AB  - Brain/kidney (B/K) protein is a novel double C2-like-domain protein that is
      highly expressed in rat brain and kidney, but its cellular localization and
      functional role in the kidney are still undetermined. We examined the cellular
      localization of B/K protein in the rat kidney under normal and ischemic
      conditions. Ischemia-reperfusion (I/R) injury was induced by clamping both renal
      arteries for 45 min, and animals were killed at 1 and 6 h and 1, 2, 3, 5, 7, 14,
      and 28 days after the reperfusion. Kidney tissues were processed for
      immunohistochemistry and immunoblot analyses using rabbit anti-B/K polyclonal
      antibodies. In control kidneys, B/K protein was expressed primarily in distal
      tubules including the thick ascending limb, distal convoluted and connecting
      tubules, and collecting duct. Notably, B/K protein was also expressed in the
      straight portion (S3 segment), but not in the S1 or S2, of proximal tubules, and
      podocytes of the glomerulus. In rat kidneys with I/R injury, expression of B/K
      protein was differentially regulated according to the anatomic location. In
      distal tubules, overall expression of B/K protein was markedly decreased. On the
      other hand, I/R injury significantly increased B/K protein expression in the S3
      segment of the outer medulla as well as in the rat proximal tubular epithelial
      cell line NRK-52E in vitro. Furthermore, B/K protein was strongly expressed in
      many exfoliated cells in the lumen and urine. These findings suggest that B/K
      protein is closely associated with cell death in proximal tubules, which are
      vulnerable to I/R injury in the kidney.

PMID- 16896194
TI  - Adolescent male bullies, victims, and bully-victims: a comparison of psychosocial
      and behavioral characteristics.
AB  - OBJECTIVE: To determine among male adolescents whether bully-victims would report
      the poorest psychosocial health, the worst attitudes toward school, more problem
      behavior (delinquency, weapons possession, and substance use), and more physical
      injury compared with bullies, victims, and neutral students. We also assessed
      ethnic differences in bullying category membership. METHODS: Employing
      multisample latent variable models, we contrasted 1,312 males in grades 7-12
      classified as bullies (n = 299), victims (n = 180), bully-victims (n = 195), and
      neutral (n = 638) on school attitudes, psychosocial health, problem behaviors,
      and physical injury. RESULTS: Hypotheses were generally confirmed, especially
      contrasts between bully-victims and neutrals. However, bullies did not have
      better school attitudes than bully-victims, and victims only marginally reported
      better psychological health than bully-victims. The boys of mixed ethnicity were
      more likely to be victims. CONCLUSIONS: Greater awareness of the problems
      associated with boys who both bully and are victimized is necessary for improved
      intervention.

PMID- 16896193
TI  - Socioeconomic status, race, and body mass index: the mediating role of physical
      activity and sedentary behaviors during adolescence.
AB  - OBJECTIVE: To assess how sociodemographic and activity behaviors contribute to
      adolescent body mass index (BMI). METHODS: One hundred and thirteen adolescents
      (M = 17 years; 42% Caucasian, 56% African American) were assessed on BMI. Teens
      reported activity levels and caregivers reported socioeconomic status (SES).
      RESULTS: Adolescents from lower SES backgrounds, and from minority groups, had
      higher BMI (r = -.26, p < .01 and t(110) = -3.01, p < .01). Formal statistical
      mediation tests revealed that sedentary behaviors significantly mediated the
      association between SES and BMI (Z = 2.31, p < .05), whereas physical activity
      significantly mediated the race-BMI association (Z = 2.32, p < .05). CONCLUSIONS:
      Interventions targeting teen BMI could benefit by aiming to decrease sedentary
      behavior in low SES teens and increase physical activity in teens from minority
      groups.

PMID- 16896195
TI  - Peripheral analgesic receptor systems.

PMID- 16896196
TI  - Four and a fifth and all that.

PMID- 16896197
TI  - Tension hydrothorax induced by central venous catheter migration in a patient
      with burns.

PMID- 16896198
TI  - Caesarean section in a patient with torsion dystonia.

PMID- 16896199
TI  - The preconditioning effects of levosimendan.

PMID- 16896200
TI  - Uvula necrosis--an unusual cause of severe postoperative sore throat.

PMID- 16896201
TI  - Morphine-induced pruritus after spinal anaesthesia.

PMID- 16896202
TI  - Imaging of the axillary vein.

PMID- 16896203
TI  - Algae need their vitamins.

PMID- 16896205
TI  - Characterization and developmentally regulated localization of the mitochondrial
      carrier protein homologue MCP6 from Trypanosoma brucei.
AB  - Proteins of the mitochondrial carrier family (MCF) are located mainly in the
      inner mitochondrial membrane and mediate the transport of a large range of
      metabolic intermediates. The genome of Trypanosoma brucei harbors 29 genes
      encoding different MCF proteins. We describe here the characterization of MCP6, a
      novel T. brucei MCF protein. Sequence comparison and phylogenetic reconstruction
      revealed that MCP6 is closely related to different mitochondrial ADP/ATP and
      calcium-dependent solute carriers, including the ATP-Mg/Pi carrier of Homo
      sapiens. However, MCP6 lacks essential amino acids and sequence motifs conserved
      in these metabolite transporters, and functional reconstitution and transport
      assays with E. coli suggested that this protein indeed does not function as an
      ADP/ATP or ATP-Mg/Pi carrier. The subcellular localization of MCP6 is
      developmentally regulated: in bloodstream-form trypanosomes, the protein is
      predominantly glycosomal, whereas in the procyclic form, it is found mainly in
      the mitochondria. Depletion of MCP6 in procyclic trypanosomes resulted in growth
      inhibition, an increased cell size, aberrant numbers of nuclei and kinetoplasts,
      and abnormal kinetoplast morphology, suggesting that depletion of MCP6 inhibits
      division of the kinetoplast.

PMID- 16896204
TI  - Circadian rhythms in Neurospora crassa and other filamentous fungi.

PMID- 16896206
TI  - Programmed transcription of the var gene family, but not of stevor, in Plasmodium
      falciparum gametocytes.
AB  - The var genes encode Plasmodium falciparum erythrocyte membrane protein 1
      (PfEMP1) proteins, a set of highly diverse surface-expressed proteins that
      mediate adhesion of erythrocytes infected with asexual blood-stage parasites to
      host endothelium. Switching among expressed PfEMP1 variants in the course of a
      blood-stage infection is a key component of antigenic variation, and thus immune
      evasion, by the parasite. The majority of var loci are found in the subtelomeric
      regions of P. falciparum chromosomes associated with members of other multigene
      families, including stevor. Both PfEMP1 and STEVOR are expressed in gametocytes,
      the transmissible parasite stage, but the role of these proteins in the biology
      of sexual-stage parasites remains unknown. PfEMP1 may continue to mediate
      antigenic variation in gametocytes, which need to persist in the host for many
      days before reaching maturity. Using quantitative reverse transcription-PCR and
      Northern hybridization, we demonstrate that transcription of a defined subset of
      type C var loci occurs during gametocyte development in vitro. This
      transcriptional program occurs in gametocytes regardless of the var expression
      phenotype of their asexual progenitors and therefore is subject to regulatory
      processes distinct from those that manage antigenic variation in the asexual
      parasite. In contrast, the same stevor variants are transcribed in both
      gametocytes and their asexual progenitors. We also provide evidence that for both
      asexual parasites and gametocytes, var and stevor transcription patterns are not
      linked to each other.

PMID- 16896208
TI  - Sorting signals required for trafficking of the cysteine-rich acidic repetitive
      transmembrane protein in Trypanosoma brucei.
AB  - In trypanosomatids, endocytosis and exocytosis are restricted to the flagellar
      pocket (FP). The cysteine-rich acidic repetitive transmembrane (CRAM) protein is
      located at the FP of Trypanosoma brucei and potentially functions as a receptor
      or an essential component for lipoprotein uptake. We characterized sorting
      determinants involved in efficient trafficking of CRAM to and from the FP of T.
      brucei. Previous studies indicated the presence of signals in the CRAM C
      terminus, specific for its localization to the FP and for efficient endocytosis
      (H. Yang, D. G. Russell, B. Zeng, M. Eiki, and M.G.-S. Lee, Mol. Cell. Biol.
      20:5149-5163, 2000.) To delineate functional domains of putative sorting signals,
      we performed a mutagenesis series of the CRAM C terminus. Subcellular
      localization of CRAM mutants demonstrated that the amino acid sequence between -5
      and -14 (referred to as a transport signal) is essential for exporting CRAM from
      the endoplasmic reticulum to the FP, and mutations of amino acids at -12 (V), -10
      (V), or -5 (D) led to retention of CRAM in the endoplasmic reticulum. Comparison
      of the endocytosis efficiency of CRAM mutants demonstrated that the sequence from
      amino acid -5 to -23 (referred to as a putative endocytosis signal) is required
      for efficient endocytosis and overlaps with the transport signal. Apparently the
      CRAM-derived sorting signal can efficiently interact with the T. brucei micro1
      adaptin, and mutations at amino acids essential for the function of the transport
      signal abolished the interaction of the signal with T. brucei micro1,
      strengthening the hypothesis of the involvement of the clathrin- and adaptor
      dependent pathway in trafficking of CRAM via the FP.

PMID- 16896207
TI  - Analysis of mitogen-activated protein kinase signaling specificity in response to
      hyperosmotic stress: use of an analog-sensitive HOG1 allele.
AB  - When confronted with a marked increase in external osmolarity, budding yeast
      (Saccharomyces cerevisiae) cells utilize a conserved mitogen-activated protein
      kinase (MAPK) signaling cascade (the high-osmolarity glycerol or HOG pathway) to
      elicit cellular responses necessary to permit continued growth. One input that
      stimulates the HOG pathway requires the integral membrane protein and putative
      osmosensor Sho1, which recruits and enables activation of the MAPK kinase kinase
      Ste11. In mutants that lack the downstream MAPK kinase (pbs2Delta) or the MAPK
      (hog1Delta) of the HOG pathway, Ste11 activated by hyperosmotic stress is able to
      inappropriately stimulate the pheromone response pathway. This loss of signaling
      specificity is known as cross talk. To determine whether it is the Hog1
      polypeptide per se or its kinase activity that is necessary to prevent cross
      talk, we constructed a fully functional analog-sensitive allele of HOG1 to permit
      acute inhibition of this enzyme without other detectable perturbations of the
      cell. We found that the catalytic activity of Hog1 is required continuously to
      prevent cross talk between the HOG pathway and both the pheromone response and
      invasive growth pathways. Moreover, contrary to previous reports, we found that
      the kinase activity of Hog1 is necessary for its stress-induced nuclear import.
      Finally, our results demonstrate a role for active Hog1 in maintaining signaling
      specificity under conditions of persistently high external osmolarity.

PMID- 16896209
TI  - Antagonism between two mechanisms of antifungal drug resistance.
AB  - This study tested for interaction between two independently evolved mechanisms of
      fluconazole resistance in Saccharomyces cerevisiae. One set of strains was from a
      400-generation evolution experiment, during which the concentration of
      fluconazole was increased from 16 to 256 microg/ml in four increments. At 100
      generations, populations became fixed for resistance mutations in either of two
      transcriptional regulators, PDR1 or PDR3. At 400 generations, replicate
      populations became fixed for another resistance mutation in UNK1, an unmapped
      gene further increasing resistance. Another genotype used in this study came from
      a population placed initially in 128 microg/ml of fluconazole; this environment
      selects for resistance through loss of function at ERG3, resulting in altered
      sterol metabolism. Mutant strains carrying PDR1(r) or PDR3(r) were crossed with
      the erg3(r) mutant strain, and the doubly mutant, haploid offspring were
      identified. The double-mutant strains grew less well than the parent strains at
      all concentrations of fluconazole tested. In genome-wide assays of gene
      expression, several ABC transporter genes that were overexpressed in one parent
      and several ERG genes that were overexpressed in the other parent were also
      overexpressed in the double mutants. Of the 43 genes that were consistently
      overexpressed in the PDR1(r) parents at generation 100, however, 31 were not
      consistently overexpressed in the double mutants. Of these 31 genes, 30 were also
      not consistently overexpressed after a further 300 generations of evolution in
      the PDR1(r) parent populations. The two independently evolved mechanisms of
      fluconazole resistance are strongly antagonistic to one another.

PMID- 16896210
TI  - Transcript profiles of Candida albicans cortical actin patch mutants reflect
      their cellular defects: contribution of the Hog1p and Mkc1p signaling pathways.
AB  - In Candida albicans, Myo5p and Sla2p are required for the polarized localization
      and function of cortical actin patches, for hyphal formation, and for
      endocytosis. Deletion of either the MYO5 or the SLA2 gene generated a common
      transcriptional response that involved changes in the transcript levels of cell
      wall protein- and membrane protein-encoding genes. However, these profiles were
      distinct from those observed for a mutant with specific deletions of the actin
      organizing domains of Myo5p or for wild-type cells treated with cytochalasin A,
      both of which also generate defects in the organization of cortical actin
      patches. The profiles observed for the myo5Delta and sla2Delta mutants had
      similarities to those of wild-type cells subjected to an osmotic shock, and the
      defects in cortical patch function found with myo5Delta and sla2Delta mutants,
      but not cortical actin patch distribution per se, affected sensitivity to various
      stresses, including heat and osmotic shocks and cell wall damage. Secondary
      effects coupled with defective endocytosis, such as lack of polarized lipid rafts
      and associated protein Rvs167-GFP (where GFP is green fluorescent protein) and
      lack of polarized wall remodeling protein GFP-Gsc1, were also observed for the
      myo5Delta and sla2Delta mutants. The mitogen-activated protein kinases Hog1p and
      Mkc1p, which mediate signaling in response to osmotic stress and cell wall
      damage, do not play a major role in regulating the transcript level changes in
      the myo5Delta and sla2Delta mutants. Hog1p was not hyperphosphorylated in the
      myo5Delta and sla2Delta mutants, and the transcript levels of only a subset of
      genes affected in the myo5Delta mutant were dependent upon the presence of Hog1p
      and Mkc1p. However, it appears that Hog1p and Mkc1p play important roles in the
      myo5Delta mutant cells because double deletion of myosin I and either Hog1p or
      Mkc1p resulted in very-slow-growing cells.

PMID- 16896211
TI  - The Opi1p transcription factor affects expression of FLO11, mat formation, and
      invasive growth in Saccharomyces cerevisiae.
AB  - Mat formation in the bakers' yeast Saccharomyces cerevisiae is a surface
      associated phenomenon in which yeast cells spread over the surface of a low
      density agar petri plate as a complex film. This spreading growth occurs by
      sliding motility and is dependent on the adhesion protein (adhesin) Flo11p. In
      order to identify molecular pathways that govern mat formation, whole-genome
      transcriptional profiling was used to compare cells growing as a mat to cells
      growing in a suspension culture (planktonic cells). This analysis revealed that
      S. cerevisiae upregulates a subset of genes in response to growth on a surface.
      These genes included the INO1 gene, which encodes the myo-inositol-1-phosphate
      synthase, which carries out the rate-limiting step in inositol biosynthesis.
      Further inquiry revealed that a transcription factor that controls INO1
      expression, called Opi1p, participates in the regulation of mat formation. Opi1p
      appears to modulate mat formation by influencing the expression of FLO11. The
      opi1Delta mutant was found to exhibit reduced FLO11 levels. Consequently, the
      opi1Delta mutant perturbs the FLO11-dependent phenotype of invasive growth. The
      opi1Delta mutant's defects in mat formation and invasive growth are dependent on
      the transcriptional activator Ino2p. These results indicate that Opi1p affects
      mat formation and invasive growth by participating in the regulation of FLO11.

PMID- 16896212
TI  - In vitro generation of human high-density-lipoprotein-resistant Trypanosoma
      brucei brucei.
AB  - The host range of African trypanosomes is influenced by innate protective
      molecules in the blood of primates. A subfraction of human high-density
      lipoprotein (HDL) containing apolipoprotein A-I, apolipoprotein L-I, and
      haptoglobin-related protein is toxic to Trypanosoma brucei brucei but not the
      human sleeping sickness parasite Trypanosoma brucei rhodesiense. It is thought
      that T. b. rhodesiense evolved from a T. b. brucei-like ancestor and expresses a
      defense protein that ablates the antitrypanosomal activity of human HDL. To
      directly investigate this possibility, we developed an in vitro selection to
      generate human HDL-resistant T. b. brucei. Here we show that conversion of T. b.
      brucei from human HDL sensitive to resistant correlates with changes in the
      expression of the variant surface glycoprotein (VSG) and abolished uptake of the
      cytotoxic human HDLs. Complete transcriptome analysis of the HDL-susceptible and 
      resistant trypanosomes confirmed that VSG switching had occurred but failed to
      reveal the expression of other genes specifically associated with human HDL
      resistance, including the serum resistance-associated gene (SRA) of T. b.
      rhodesiense. In addition, we found that while the original active expression site
      was still utilized, expression of three expression site-associated genes (ESAG)
      was altered in the HDL-resistant trypanosomes. These findings demonstrate that
      resistance to human HDLs can be acquired by T. b. brucei.

PMID- 16896214
TI  - Spo5/Mug12, a putative meiosis-specific RNA-binding protein, is essential for
      meiotic progression and forms Mei2 dot-like nuclear foci.
AB  - We report here a functional analysis of spo5(+)(mug12(+)) of Schizosaccharomyces
      pombe, which encodes a putative RNA-binding protein. The disruption of spo5(+)
      caused abnormal sporulation, generating inviable spores due to failed forespore
      membrane formation and the absence of a spore wall, as determined by electron
      microscopy. Spo5 regulates the progression of meiosis I because spo5 mutant cells
      display normal premeiotic DNA synthesis and the timely initiation of meiosis I
      but they show a delay in the peaking of cells with two nuclei, abnormal tyrosine
      15 dephosphorylation of Cdc2, incomplete degradation of Cdc13, retarded formation
      and repair of double strand breaks, and a reduced frequency of intragenic
      recombination. Immunostaining showed that Spo5-green fluorescent protein (GFP)
      appeared in the cytoplasm at the horsetail phase, peaked around the metaphase I
      to anaphase I transition, and suddenly disappeared after anaphase II. Images of
      Spo5-GFP in living cells revealed that Spo5 forms a dot in the nucleus at
      prophase I that colocalized with the Mei2 dot. Unlike the Mei2 dot, however, the
      Spo5 dot was observed even in sme2Delta cells. Taken together, we conclude that
      Spo5 is a novel regulator of meiosis I and that it may function in the vicinity
      of the Mei2 dot.

PMID- 16896213
TI  - GPR-4 is a predicted G-protein-coupled receptor required for carbon source
      dependent asexual growth and development in Neurospora crassa.
AB  - The filamentous fungus Neurospora crassa is able to utilize a wide variety of
      carbon sources. Here, we examine the involvement of a predicted G-protein-coupled
      receptor (GPCR), GPR-4, during growth and development in the presence of
      different carbon sources in N. crassa. Deltagpr-4 mutants have reduced mass
      accumulation compared to the wild type when cultured on high levels of glycerol,
      mannitol, or arabinose. The defect is most severe on glycerol and is cell density
      dependent. The genetic and physical relationship between GPR-4 and the three N.
      crassa Galpha subunits (GNA-1, GNA-2, and GNA-3) was explored. All three Galpha
      mutants are defective in mass accumulation when cultured on glycerol. However,
      the phenotypes of Deltagna-1 and Deltagpr-4 Deltagna-1 mutants are identical,
      introduction of a constitutively activated gna-1 allele suppresses the defects of
      the Deltagpr-4 mutation, and the carboxy terminus of GPR-4 interacts most
      strongly with GNA-1 in the yeast two-hybrid assay. Although steady-state cyclic
      AMP (cAMP) levels are normal in Deltagpr-4 strains, exogenous cAMP partially
      remediates the dry mass defects of Deltagpr-4 mutants on glycerol medium and
      Deltagpr-4 strains lack the transient increase in cAMP levels observed in the
      wild type after addition of glucose to glycerol-grown liquid cultures. Our
      results support the hypothesis that GPR-4 is coupled to GNA-1 in a cAMP signaling
      pathway that regulates the response to carbon source in N. crassa. GPR-4-related
      GPCRs are present in the genomes of several filamentous ascomycete fungal
      pathogens, raising the possibility that a similar pathway regulates carbon
      sensing in these organisms.

PMID- 16896216
TI  - Functional analysis of the ATG8 homologue Aoatg8 and role of autophagy in
      differentiation and germination in Aspergillus oryzae.
AB  - Autophagy is a well-known degradation system, induced by nutrient starvation, in
      which cytoplasmic components and organelles are digested via vacuoles/lysosomes.
      Recently, it was reported that autophagy is involved in the turnover of cellular
      components, development, differentiation, immune responses, protection against
      pathogens, and cell death. In this study, we isolated the ATG8 gene homologue
      Aoatg8 from the filamentous fungus Aspergillus oryzae and visualized autophagy by
      the expression of DsRed2-AoAtg8 and enhanced green fluorescent protein-AoAtg8
      fusion proteins in this fungus. While the fusion proteins were localized in dot
      structures which are preautophagosomal structure-like structures under normal
      growth conditions, starvation or rapamycin treatment caused their accumulation in
      vacuoles. DsRed2 expressed in the cytoplasm was also taken up into vacuoles under
      starvation conditions or during the differentiation of conidiophores and conidial
      germination. Deletion mutants of Aoatg8 did not form aerial hyphae and conidia,
      and DsRed2 was not localized in vacuoles under starvation conditions, indicating
      that Aoatg8 is essential for autophagy. Furthermore, Aoatg8 conditional mutants
      showed delayed conidial germination in the absence of nitrogen sources. These
      results suggest that autophagy functions in both the differentiation of aerial
      hyphae and in conidial germination in A. oryzae.

PMID- 16896215
TI  - Import-associated translational inhibition: novel in vivo evidence for
      cotranslational protein import into Dictyostelium discoideum mitochondria.
AB  - To investigate protein import into the mitochondria of Dictyostelium discoideum,
      green fluorescent protein (GFP) was fused as a reporter protein either to
      variable lengths of the N-terminal region of chaperonin 60 (the first 23, 40, 80,
      97, and 150 amino acids) or to the mitochondrial targeting sequence of DNA
      topoisomerase II. The fusion proteins were expressed in AX2 cells under the actin
      15 promoter. Fluorescence images of GFP transformants confirmed that
      Dictyostelium chaperonin 60 is a mitochondrial protein. The level of the
      mitochondrially targeted GFP fusion proteins was unexpectedly much lower than the
      nontargeted (cytoplasmic) forms. The distinction between targeted and nontargeted
      protein activities was investigated at both the transcriptional and translational
      levels in vivo. We found that targeting GFP to the mitochondria results in
      reduced levels of the fusion protein even though transcription of the fusion gene
      and the stability of the protein are unaffected. [(35)S]methionine labeling and
      GFP immunoprecipitation confirmed that mitochondrially targeted GFP is translated
      at much slower rates than nontargeted GFP. The results indicate a novel
      phenomenon, import-associated translational inhibition, whereby protein import
      into the mitochondria limits the rate of translation. The simplest explanation
      for this is that import of the GFP fusion proteins occurs cotranslationally,
      i.e., protein synthesis and import into mitochondria are coupled events.
      Consistent with cotranslational import, Northern analysis showed that the GFP
      mRNA is associated with isolated mitochondria. This association occurred
      regardless of whether the GFP was fused to a mitochondrial leader peptide.
      However, the presence of an import-competent leader peptide stabilized the mRNA
      mitochondria association, rendering it more resistant to extensive EDTA washing.
      In contrast with GFP, the mRNA of another test protein, aequorin, did not
      associate with the mitochondria, and its translation was unaffected by import of
      the encoded polypeptide into the mitochondria.

PMID- 16896217
TI  - Stress-specific role of fission yeast Gcn5 histone acetyltransferase in
      programming a subset of stress response genes.
AB  - Gcn5 is a coactivator protein that contributes to gene activation by acetylating
      specific lysine residues within the N termini of histone proteins. Gcn5 has been
      intensively studied in the budding yeast, Saccharomyces cerevisiae, but the
      features of genes that determine whether they require Gcn5 during activation have
      not been conclusively clarified. To allow comparison with S. cerevisiae, we have
      studied the genome-wide role of Gcn5 in the distantly related fission yeast,
      Schizosaccharomyces pombe. We show that Gcn5 is specifically required for
      adaptation to KCl- and CaCl(2)-mediated stress in S. pombe. We have characterized
      the genome-wide gene expression responses to KCl stress and show that Gcn5 is
      involved in the regulation of a subset of stress response genes. Gcn5 is most
      clearly associated with KCl-induced genes, but there is no correlation between
      Gcn5 dependence and the extent of their induction. Instead, Gcn5-dependent KCl
      induced genes are specifically enriched in four different DNA motifs. The Gcn5
      dependent KCl-induced genes are also associated with biological process gene
      ontology terms such as carbohydrate metabolism, glycolysis, and nicotinamide
      metabolism that together constitute a subset of the ontology parameters
      associated with KCl-induced genes.

PMID- 16896218
TI  - Molecular genetic analysis of an SNF2/brahma-related gene in Tetrahymena
      thermophila suggests roles in growth and nuclear development.
AB  - We used a reverse genetic approach to identify three members of the SNF2
      superfamily of chromatin remodeling genes in the ciliated protozoan Tetrahymena
      thermophila in order to investigate possible functions of ATP-dependent chromatin
      remodeling factors in growth and nuclear development. Comparative sequence
      analysis of the gene product of the Tetrahymena brahma-related gene (TtBRG1)
      indicates it is a member of the SNF2/BRM subgroup of the SNF2 superfamily.
      Northern analysis suggests that TtBRG1 has roles in growth and nuclear
      development in Tetrahymena. Indirect immunofluorescence analysis during nuclear
      development indicates that TtBrg1p localizes to both the parental and developing
      macronucleus of Tetrahymena during the time period corresponding to genome
      rearrangements. We generated germ line knockout heterokaryons for TtBRG1 and
      demonstrated that expression of the gene is required to complete nuclear
      development of Tetrahymena. In addition, the formation of distinct Pdd1p
      containing structures is disturbed during the late stages of conjugation in
      TtBRG1 germ line knockout heterokaryons. We discuss these results in light of
      possible roles of SNF2-related proteins in growth and nuclear development of
      Tetrahymena.

PMID- 16896219
TI  - Transcriptomic analysis of extensive changes in metabolic regulation in
      Kluyveromyces lactis strains.
AB  - Genome-wide analysis of transcriptional regulation is generally carried out on
      well-characterized reference laboratory strains; hence, the characteristics of
      industrial isolates are therefore overlooked. In a previous study on the major
      cheese yeast Kluyveromyces lactis, we have shown that the reference strain and an
      industrial strain used in cheese making display a differential gene expression
      when grown on a single carbon source. Here, we have used more controlled
      conditions, i.e., growth in a fermentor with pH and oxygen maintained constant,
      to study how these two isolates grown in glucose reacted to an addition of
      lactose. The observed differences between sugar consumption and the production of
      various metabolites, ethanol, acetate, and glycerol, correlated with the response
      were monitored by the analysis of the expression of 482 genes. Extensive
      differences in gene expression between the strains were revealed in sugar
      transport, glucose repression, ethanol metabolism, and amino acid import. These
      differences were partly due to repression by glucose and another, yet-unknown
      regulation mechanism. Our results bring to light a new type of K. lactis strain
      with respect to hexose transport gene content and repression by glucose. We found
      that a combination of point mutations and variation in gene regulation generates
      a biodiversity within the K. lactis species that was not anticipated. In contrast
      to S. cerevisiae, in which there is a massive increase in the number of sugar
      transporter and fermentation genes, in K. lactis, interstrain diversity in
      adaptation to a changing environment is based on small changes at the level of
      key genes and cell growth control.

PMID- 16896220
TI  - Effects of depleting the essential central metabolic enzyme fructose-1,6
      bisphosphate aldolase on the growth and viability of Candida albicans:
      implications for antifungal drug target discovery.
AB  - The central metabolic enzyme fructose-1,6-bisphosphate aldolase (Fba1p) catalyzes
      a reversible reaction required for both glycolysis and gluconeogenesis. Fba1p is
      a potential antifungal target because it is essential in yeast and because fungal
      and human aldolases differ significantly. To test the validity of Fba1p as an
      antifungal target, we have examined the effects of depleting this enzyme in the
      major fungal pathogen Candida albicans. Using a methionine/cysteine-conditional
      mutant (MET3-FBA1/fba1), we have shown that Fba1p is required for the growth of
      C. albicans. However, Fba1p must be depleted to below 5% of wild-type levels
      before growth is blocked. Furthermore, Fba1p depletion exerts static rather than
      cidal effects upon C. albicans. Fba1p is a relatively abundant and stable protein
      in C. albicans, and hence, Fba1p levels decay relatively slowly following MET3
      FBA1 shutoff. Taken together, our observations can account for our observation
      that the virulence of MET3-FBA1/fba1 cells is only partially attenuated in the
      mouse model of systemic candidiasis. We conclude that an antifungal drug directed
      against Fba1p would have to be potent to be effective.

PMID- 16896221
TI  - Eukaryotic release factor 1 phosphorylation by CK2 protein kinase is dynamic but
      has little effect on the efficiency of translation termination in Saccharomyces
      cerevisiae.
AB  - Protein synthesis requires a large commitment of cellular resources and is highly
      regulated. Previous studies have shown that a number of factors that mediate the
      initiation and elongation steps of translation are regulated by phosphorylation.
      In this report, we show that a factor involved in the termination step of protein
      synthesis is also subject to phosphorylation. Our results indicate that
      eukaryotic release factor 1 (eRF1) is phosphorylated in vivo at serine 421 and
      serine 432 by the CK2 protein kinase (previously casein kinase II) in the budding
      yeast Saccharomyces cerevisiae. Phosphorylation of eRF1 has little effect on the
      efficiency of stop codon recognition or nonsense-mediated mRNA decay. Also,
      phosphorylation is not required for eRF1 binding to the other translation
      termination factor, eRF3. In addition, we provide evidence that the putative
      phosphatase Sal6p does not dephosphorylate eRF1 and that the state of eRF1
      phosphorylation does not influence the allosuppressor phenotype associated with a
      sal6Delta mutation. Finally, we show that phosphorylation of eRF1 is a dynamic
      process that is dependent upon carbon source availability. Since many other
      proteins involved in protein synthesis have a CK2 protein kinase motif near their
      extreme C termini, we propose that this represents a common regulatory mechanism
      that is shared by factors involved in all three stages of protein synthesis.

PMID- 16896222
TI  - Heterologous expression implicates a GATA factor in regulation of nitrogen
      metabolic genes and ion homeostasis in the halotolerant yeast Debaryomyces
      hansenii.
AB  - The yeast Debaryomyces hansenii has a remarkable capacity to proliferate in salty
      and alkaline environments such as seawater. A screen for D. hansenii genes able
      to confer increased tolerance to high pH when overexpressed in Saccharomyces
      cerevisiae yielded a single gene, named here DhGZF3, encoding a putative negative
      GATA transcription factor related to S. cerevisiae Dal80 and Gzf3. Overexpression
      of this gene in wild-type S. cerevisiae increased caffeine and rapamycin
      tolerance, blocked growth in low glucose concentrations and nonfermentable carbon
      sources, and resulted in lithium- and sodium-sensitive cells. Sensitivity to salt
      could be attributed to a reduced cation efflux, most likely because of a decrease
      in expression of the ENA1 Na(+)-ATPase gene. Overexpression of DhGZF3 did not
      affect cell growth in a gat1 mutant but was lethal in the absence of Gln3. These
      are positive factors that oppose both Gzf3 and Dal80. Genome-wide transcriptional
      profiling of wild-type cells overexpressing DhGZF3 shows decreased expression of
      a number of genes that are usually induced in poor nitrogen sources. In addition,
      the entire pathway leading to Lys biosynthesis was repressed, probably as a
      result of a decrease in the expression of the specific Lys14 transcription
      factor. In conclusion, our results demonstrate that DhGzf3 can play a role as a
      negative GATA transcription factor when expressed in S. cerevisiae and that it
      most probably represents the only member of this family in D. hansenii. These
      findings also point to the GATA transcription factors as relevant elements for
      alkaline-pH tolerance.

PMID- 16896223
TI  - The vtc4 gene influences polyphosphate storage, morphogenesis, and virulence in
      the maize pathogen Ustilago maydis.
AB  - The maize pathogen Ustilago maydis switches from budding to filamentous,
      dikaryotic growth in response to environmental signals including nutrient status,
      growth in the host, and the presence of mating pheromones. The filamentous
      dikaryon is capable of proliferating within host tissue to cause disease symptoms
      including tumors. The transition from yeast cells to hyphal filaments is
      regulated by a mitogen-activated protein kinase cascade and a cyclic-AMP-protein
      kinase A (PKA) pathway. Serial analysis of gene expression with PKA mutants
      identified orthologs of components of the PHO phosphate acquisition pathway as
      transcriptional targets of the PKA pathway, and these included genes for Pho84,
      an acid phosphatase, and the vacuolar transport chaperones Vtc1 and Vtc4. In
      Saccharomyces cerevisiae, Vtc4p is required during the fusion of inorganic
      phosphate-containing vesicles to the vacuolar membrane and the consequent
      accumulation of phosphate stored as polyphosphate (polyP) in the vacuole. We
      found that deletion of vtc4 in U. maydis also reduced polyP stored in vacuoles.
      Intriguingly, Deltavtc4 mutants possessed a filamentous cellular morphology, in
      contrast to the budding, yeast-like growth of the wild-type parent. The Deltavtc4
      mutants also displayed decreased symptom development and reduced proliferation in
      planta. The interaction with PKA signaling was further investigated by the
      generation of Deltavtc4 ubc1 double mutants. Deletion of vtc4 completely
      suppressed the multiple-budded phenotype of a Deltaubc1 mutant, indicating that
      polyP stores are essential for this PKA-induced trait. Overall, this study
      reveals a novel role for PKA-regulated polyP accumulation in the control of
      fungal morphogenesis and virulence.

PMID- 16896224
TI  - Hog1 mitogen-activated protein kinase plays conserved and distinct roles in the
      osmotolerant yeast Torulaspora delbrueckii.
AB  - Torulaspora delbrueckii has emerged during evolution as one of the most
      osmotolerant yeasts. However, the molecular mechanisms underlying this unusual
      stress resistance are poorly understood. In this study, we have characterized the
      functional role of the high-osmolarity glycerol (HOG) mitogen-activated protein
      kinase pathway in mediating the osmotic stress response, among others, in T.
      delbrueckii. We show that the T. delbrueckii Hog1p homologue TdHog1p is
      phosphorylated after cell transfer to NaCl- or sorbitol-containing medium.
      However, TdHog1p plays a minor role in tolerance to conditions of moderate
      osmotic stress, a trait related mainly with the osmotic balance. In consonance
      with this, the absence of TdHog1p produced only a weak defect in the timing of
      the osmostress-induced glycerol and GPD1 mRNA overaccumulation. Tdhog1Delta
      mutants also failed to display aberrant morphology changes in response to osmotic
      stress. Furthermore, our data indicate that the T. delbrueckii HOG pathway has
      evolved to respond to specific environmental conditions and to play a pivotal
      role in the stress cross-protection mechanism.

PMID- 16896225
TI  - Membrane topology and transient acylation of Toxoplasma gondii
      glycosylphosphatidylinositols.
AB  - Using hypotonically permeabilized Toxoplasma gondii tachyzoites, we investigated
      the topology of the free glycosylphosphatidylinositols (GPIs) within the
      endoplasmic reticulum (ER) membrane. The morphology and permeability of parasites
      were checked by electron microscopy and release of a cytosolic protein. The
      membrane integrity of organelles (ER and rhoptries) was checked by protease
      protection assays. In initial experiments, GPI biosynthetic intermediates were
      labeled with UDP-[6-(3)H]GlcNAc in permeabilized parasites, and the transmembrane
      distribution of the radiolabeled lipids was probed with phosphatidylinositol
      specific phospholipase C (PI-PLC). A new early intermediate with an acyl
      modification on the inositol was identified, indicating that inositol acylation
      also occurs in T. gondii. A significant portion of the early GPI intermediates
      (GlcN-PI and GlcNAc-PI) could be hydrolyzed following PI-PLC treatment,
      indicating that these glycolipids are predominantly present in the cytoplasmic
      leaflet of the ER. Permeabilized T. gondii parasites labeled with either GDP-[2
      (3)H]mannose or UDP-[6-(3)H]glucose showed that the more mannosylated and side
      chain (Glc-GalNAc)-modified GPI intermediates are also preferentially localized
      in the cytoplasmic leaflet of the ER.

PMID- 16896227
TI  - Fungal metabolic model for tyrosinemia type 3: molecular characterization of a
      gene encoding a 4-hydroxy-phenyl pyruvate dioxygenase from Aspergillus nidulans.
AB  - Mutations in the human HPD gene (encoding 4-hydroxyphenylpyruvic acid
      dioxygenase) cause hereditary tyrosinemia type 3 (HT3). We deleted the
      Aspergillus nidulans homologue (hpdA). We showed that the mutant strain is not
      able to grow in the presence of phenylalanine and that it accumulates increased
      concentrations of tyrosine and 4-hydroxyphenylpyruvic acid, mimicking the human
      HT3 phenotype.

PMID- 16896226
TI  - Trypanosoma congolense procyclins: unmasking cryptic major surface glycoproteins
      in procyclic forms.
AB  - In the tsetse fly, the protozoan parasite Trypanosoma congolense is covered by a
      dense layer of glycosylphosphatidylinositol (GPI)-anchored molecules. These
      include a protease-resistant surface molecule (PRS), which is expressed by
      procyclic forms early in infection, and a glutamic acid- and alanine-rich protein
      (GARP), which appears at later stages. Since neither of these surface antigens is
      expressed at intermediate stages, we investigated whether a GPI-anchored protein
      of 50 to 58 kDa, previously detected in procyclic culture forms, might constitute
      the coat of these parasites. We therefore partially purified the protein from T.
      congolense Kilifi procyclic forms, obtained an N-terminal amino acid sequence,
      and identified its gene. Detailed analyses showed that the mature protein
      consists almost exclusively of 13 heptapeptide repeats (EPGENGT). The protein is
      densely N glycosylated, with up to 13 high-mannose oligosaccharides ranging from
      Man(5)GlcNAc(2) to Man(9)GlcNAc(2) linked to the peptide repeats. The lipid
      moiety of the glycosylphosphatidylinositol is composed of sn-1-stearoyl-2-lyso
      glycerol-3-HPO(4)-1-(2-O-acyl)-d-myo-inositol. Heavily glycosylated proteins with
      similar repeats were subsequently identified in T. congolense Savannah procyclic
      forms. Collectively, this group of proteins was named T. congolense procyclins to
      reflect their relationship to the EP and GPEET procyclins of T. brucei. Using an
      antiserum raised against the EPGENGT repeat, we show that T. congolense
      procyclins are expressed continuously in the fly midgut and thus form the surface
      coat of cells that are negative for both PRS and GARP.

PMID- 16896229
TI  - Genevestigator. Facilitating web-based gene-expression analysis.

PMID- 16896231
TI  - Cosecretion of protease inhibitor stabilizes antibodies produced by plant roots.
AB  - A plant-based system for continuous production of monoclonal antibodies based on
      the secretion of immunoglobulin complexes from plant roots into a hydroponic
      medium (rhizosecretion) was engineered to produce high levels of single-chain and
      full-size immunoglobulins. Replacing the original signal peptides of monoclonal
      antibodies with a plant-derived calreticulin signal increased the levels of
      antibody yield 2-fold. Cosecretion of Bowman-Birk Ser protease inhibitor reduced
      degradation of the immunoglobulin complexes in the default secretion pathway and
      further increased antibody production to 36.4 microg/g root dry weight per day
      for single-chain IgG1 and 21.8 microg/g root dry weight per day for full-size
      IgG4 antibodies. These results suggest that constitutive cosecretion of a
      protease inhibitor combined with the use of the plant signal peptide and the
      antibiotic marker-free transformation system offers a novel strategy to achieve
      high yields of complex therapeutic proteins secreted from plant roots.

PMID- 16896230
TI  - Genome-wide analysis of basic/helix-loop-helix transcription factor family in
      rice and Arabidopsis.
AB  - The basic/helix-loop-helix (bHLH) transcription factors and their homologs form a
      large family in plant and animal genomes. They are known to play important roles
      in the specification of tissue types in animals. On the other hand, few plant
      bHLH proteins have been studied functionally. Recent completion of whole genome
      sequences of model plants Arabidopsis (Arabidopsis thaliana) and rice (Oryza
      sativa) allows genome-wide analysis and comparison of the bHLH family in
      flowering plants. We have identified 167 bHLH genes in the rice genome, and their
      phylogenetic analysis indicates that they form well-supported clades, which are
      defined as subfamilies. In addition, sequence analysis of potential DNA-binding
      activity, the sequence motifs outside the bHLH domain, and the conservation of
      intron/exon structural patterns further support the evolutionary relationships
      among these proteins. The genome distribution of rice bHLH genes strongly
      supports the hypothesis that genome-wide and tandem duplication contributed to
      the expansion of the bHLH gene family, consistent with the birth-and-death theory
      of gene family evolution. Bioinformatics analysis suggests that rice bHLH
      proteins can potentially participate in a variety of combinatorial interactions,
      endowing them with the capacity to regulate a multitude of transcriptional
      programs. In addition, similar expression patterns suggest functional
      conservation between some rice bHLH genes and their close Arabidopsis homologs.

PMID- 16896232
TI  - A versatile and reliable two-component system for tissue-specific gene induction
      in Arabidopsis.
AB  - Developmental progression and differentiation of distinct cell types depend on
      the regulation of gene expression in space and time. Tools that allow spatial and
      temporal control of gene expression are crucial for the accurate elucidation of
      gene function. Most systems to manipulate gene expression allow control of only
      one factor, space or time, and currently available systems that control both
      temporal and spatial expression of genes have their limitations. We have
      developed a versatile two-component system that overcomes these limitations,
      providing reliable, conditional gene activation in restricted tissues or cell
      types. This system allows conditional tissue-specific ectopic gene expression and
      provides a tool for conditional cell type- or tissue-specific complementation of
      mutants. The chimeric transcription factor XVE, in conjunction with Gateway
      recombination cloning technology, was used to generate a tractable system that
      can efficiently and faithfully activate target genes in a variety of cell types.
      Six promoters/enhancers, each with different tissue specificities (including
      vascular tissue, trichomes, root, and reproductive cell types), were used in
      activation constructs to generate different expression patterns of XVE.
      Conditional transactivation of reporter genes was achieved in a predictable,
      tissue-specific pattern of expression, following the insertion of the activator
      or the responder T-DNA in a wide variety of positions in the genome. Expression
      patterns were faithfully replicated in independent transgenic plant lines.
      Results demonstrate that we can also induce mutant phenotypes using conditional
      ectopic gene expression. One of these mutant phenotypes could not have been
      identified using noninducible ectopic gene expression approaches.

PMID- 16896233
TI  - A liquid chromatography-mass spectrometry-based metabolome database for tomato.
AB  - For the description of the metabolome of an organism, the development of common
      metabolite databases is of utmost importance. Here we present the Metabolome
      Tomato Database (MoTo DB), a metabolite database dedicated to liquid
      chromatography-mass spectrometry (LC-MS)- based metabolomics of tomato fruit
      (Solanum lycopersicum). A reproducible analytical approach consisting of reversed
      phase LC coupled to quadrupole time-of-flight MS and photodiode array detection
      (PDA) was developed for large-scale detection and identification of mainly
      semipolar metabolites in plants and for the incorporation of the tomato fruit
      metabolite data into the MoTo DB. Chromatograms were processed using software
      tools for mass signal extraction and alignment, and intensity-dependent accurate
      mass calculation. The detected masses were assigned by matching their accurate
      mass signals with tomato compounds reported in literature and complemented, as
      much as possible, by PDA and MS/MS information, as well as by using reference
      compounds. Several novel compounds not previously reported for tomato fruit were
      identified in this manner and added to the database. The MoTo DB is available at
      http://appliedbioinformatics.wur.nl and contains all information so far assembled
      using this LC-PDA-quadrupole time-of-flight MS platform, including retention
      times, calculated accurate masses, PDA spectra, MS/MS fragments, and literature
      references. Unbiased metabolic profiling and comparison of peel and flesh tissues
      from tomato fruits validated the applicability of the MoTo DB, revealing that all
      flavonoids and alpha-tomatine were specifically present in the peel, while
      several other alkaloids and some particular phenylpropanoids were mainly present
      in the flesh tissue.

PMID- 16896235
TI  - How far can a molecule of weak acid travel in the apoplast or xylem?

PMID- 16896238
TI  - Topical antimicrobials in the control of wound bioburden.
AB  - Bacterial colonization and infection are important factors in compromised wound
      healing, particularly in chronic wounds. Although "best practice" for controlling
      these factors currently is not defined, systemic antibiotics are generally
      accepted as the preferred choice for treating infection, provided ischemia does
      not reduce their bioavailability. However, widespread use of systemic and topical
      antibiotics is associated with the emergence of resistant bacterial strains such
      as methicillin-resistant Staphylococcus aureus. Colonization of wounds presents a
      double problem--potentially delayed healing and a potential source for cross
      contamination. The judicious use of dressings, notably those containing certain
      antiseptic agents, can be a valuable option to control infection and promote
      healing. A review of the literature underscores the importance of considering the
      antiseptic route as part of a concerted approach to wound management and
      infection control.

PMID- 16896234
TI  - Consensus by democracy. Using meta-analyses of microarray and genomic data to
      model the cold acclimation signaling pathway in Arabidopsis.
AB  - The whole-genome response of Arabidopsis (Arabidopsis thaliana) exposed to
      different types and durations of abiotic stress has now been described by a
      wealth of publicly available microarray data. When combined with studies of how
      gene expression is affected in mutant and transgenic Arabidopsis with altered
      ability to transduce the low temperature signal, these data can be used to test
      the interactions between various low temperature-associated transcription factors
      and their regulons. We quantized a collection of Affymetrix microarray data so
      that each gene in a particular regulon could vote on whether a cis-element found
      in its promoter conferred induction (+1), repression (-1), or no transcriptional
      change (0) during cold stress. By statistically comparing these election results
      with the voting behavior of all genes on the same gene chip, we verified the
      bioactivity of novel cis-elements and defined whether they were inductive or
      repressive. Using in silico mutagenesis we identified functional binding
      consensus variants for the transcription factors studied. Our results suggest
      that the previously identified ICEr1 (induction of CBF expression region 1)
      consensus does not correlate with cold gene induction, while the ICEr3/ICEr4
      consensuses identified using our algorithms are present in regulons of genes that
      were induced coordinate with observed ICE1 transcript accumulation and temporally
      preceding genes containing the dehydration response element. Statistical analysis
      of overlap and cis-element enrichment in the ICE1, CBF2, ZAT12, HOS9, and PHYA
      regulons enabled us to construct a regulatory network supported by multiple lines
      of evidence that can be used for future hypothesis testing.

PMID- 16896240
TI  - Wound management: using Levine's conservation model to guide practice.
AB  - Effective wound management is needed not only to generate positive patient
      outcomes, but also to reduce healthcare expenditure and demand on healthcare
      services. Implementing Levine's four-principled conservation model--which
      addresses conservation of energy, structural integrity, personal integrity, and
      social integrity--can provide clinical and financial benefits, as illustrated in
      the care of venous leg ulceration. Using Levine's model as a theoretical
      framework for wound management also can contribute to good nursing practices,
      enhancing a care approach that embraces wholeness and health along with cost
      effective care. Understanding how Levine's model can improve patient care is
      further elucidated by discussing each of the principles in relation to wound
      management.

PMID- 16896239
TI  - Treatment of pressure ulcers: results of a study comparing evidence and practice.
AB  - Pressure ulcers remain prevalent in hospitals and nursing homes despite the
      availability of evidence-based guidelines for prevention and care. To evaluate
      the level of evidence-based literature and its application in pressure ulcer
      treatment, a search was conducted of relevant English and German articles
      published between 1994 and 2002 using the key terms decubitus ulcer and its
      synonyms in different combinations with therapy, wound management, and specific
      wound treatment terms. Results were compared to wound dressing use data obtained
      from two pressure ulcer prevalence surveys conducted in 51 hospitals and 15
      nursing homes in Germany in 2001 and 2002 (N = 11,584). Dressing usage evidence
      levels were reviewed and reported usage was classified as consistent or not
      consistent with existing guidelines or as evidence base unknown. Pressure ulcer
      prevalence rates ranged from 10.6% to 13.2% and the majority of pressure ulcers
      (60%) were Grade 1. In nursing homes, dressing selection was consistent with
      current evidence in 6.8% of Grade 1 and 27.8% of Grade 2 ulcers. In acute care
      facilities, dressing selection in 2001 and 2002 was consistent with current
      evidence in 21.6% and 38.5%, respectively, of Grade 1 ulcers and in 40.2% and
      51.5%, respectively, of Grade 2 ulcers. Although strong evidence exists to
      support the use of dressings that facilitate moist wound healing, barely half of
      the grade 3 and grade 4 ulcers in all care settings received this treatment.
      While dressing classification limitations restricted the ability to analyze all
      treatment methods used, findings suggest that clinician knowledge deficits
      regarding evidence-based treatments remain. The literature review results also
      indicate the level of evidence for many practice recommendations remains low.
      Studies to increase evidence levels of pressure ulcer prevention and treatment as
      well as programs to improve awareness and implementation of current evidence
      based guidelines are needed.

PMID- 16896242
TI  - Chemical speciation of trace metals in seawater: a review.
AB  - The recent development of the chemical speciation of trace metals in seawater is
      described. The speciation studies reveal that metal ion complexation is one of
      the most important processes in seawater; especially, most bioactive trace
      metals, such as Fe(III) and Cu, exist as complexes with ligands in dissolved
      organic matter. The organic ligands in seawater are characterized with metal ions
      selected by the HSAB concept. A strong organic ligand, which originates from
      marine microorganisms, is classified as a hard base including carboxylates. The
      free organic ligand concentrations in seawater are buffered by complexation with
      excess amounts of Ca and Mg in seawater. The chemical equilibrium model suggested
      that the concentrations of bioactive free metal ions are at an optimal level to
      activities of marine microorganisms. For chemical speciation, it is important to
      have a better understanding of the ecological roles of trace metals in seawater.

PMID- 16896241
TI  - Efficient precipitation of dyes from dilute aqueous solutions of ionic liquids.
AB  - The addition of only approximately 1.7 wt% (approximately 0.06 M) ionic liquid 1
      butyl-3-methylimidazolium hexafluorophosphate to aqueous solutions of six popular
      cationic dyes resulted in the precipitation of almost all of the dye from the
      solution.

PMID- 16896243
TI  - Microfluidic polymer chip integrated with an ISFET detector for cationic
      surfactant assay in dental rinses.
AB  - A cationic surfactant ion-selective field-effect transistor (cationic surfactant
      ISFET) has been developed based on the tetraphenylborate derivative known as
      sodium tetrakis[3,5-bis(trifluoromethyl)phenyl]borate. The cationic surfactant
      ISFET shows an almost Nernstian response to tetradecyldimethylbenzylammonium
      chloride (Zephiramine) over a concentration range between 1.0 x 10(-6) M and 1.0
      x 10(-3) M, with a slope of 58.5 +/- 1.7 mV/decade. The cationic surfactant-ISFET
      can be used over a range of pH values, between pH 3 and 9. The cationic
      surfactant-ISFET shows excellent selectivity for Zephiramine over small inorganic
      cations, but shows similar selectivity for other cationic surfactants, such as
      hexadecyltrimethylammonium and stearyltrimethylammonium ions. A microfluidic
      polymer chip was integrated with the cationic surfactant-ISFET, and this was
      fabricated using polystyrene plates and stainless wires as a template for the
      channel. Cationic surfactant-ISFETs used in a batch system and microchips
      integrated with cationic surfactant-ISFETs showed very similar performance in
      terms of low detection limits, slope sensitivity and the stability of the
      potential response. The microfluidic polymer chip was then applied to the
      determination of cationic surfactants in dental rinses.

PMID- 16896245
TI  - A coated wire-type lead(II) ion-selective electrode based on a phosphorylated
      calix[4]arene derivative.
AB  - The preparation of a lead-selective electrode based on 5,11,17,23-tetra-tert
      butyl-25,26,27,28-tetrakis-(diphenylphosphinoylmethoxy)calix[4]arene (1) as an
      ionophore is reported. The plasticized PVC membrane containing 30% PVC, 57% ortho
      nitrophenyloctylether (NPOE), 4% sodium tetraphenylborate (NaTPB) and 9%
      ionophore 1 was directly coated on a graphite electrode. It exhibits a nearly
      Nernstian slope of 28.0 +/- 0.2 mV decade(-1) over a concentration range of 1 x
      10(-5) - 1 x 10(-2) mol dm(-3) with a detection limit of 1.4 x 10(-6) mol dm(-3).
      The response time of the electrode was found to be ca. 17 s. The potential of the
      sensor was independent of the pH variation in the range 3.5 - 5.0. The
      selectivity of the electrode performance towards lead ions over Th4+, La3+, Sm3+,
      Dy3+, Y3+, Ca2+, Sr2+, Cd2+, Mn2+, Zn2+, Ni2+, Co2+, NH4+ Ag+, Li+, Na+ and K+
      ions was investigated. The prepared electrode was used successfully as an
      indicator electrode for a potentiometric titration of a lead solution using a
      standard solution of EDTA. The applicability of the sensor for Pb2+ measurements
      in various synthetic water samples spiked with lead nitrate was also checked.

PMID- 16896244
TI  - Direct electrochemical behavior of cytochrome c on DNA-modified glassy carbon
      electrode and its application to cytochrome c biosensor.
AB  - DNA was immobilized on glassy carbon electrodes to fabricate DNA-modified
      electrodes. The direct electron transfer of horse heart cytochrome c on DNA
      modified glassy carbon electrode was achieved. A pair of well-defined redox peaks
      of cytochrome c appeared at Epc = -0.017 V and Epa = 0.009 V (vs. Ag/AgCl) in 10
      mM phosphate buffer solution (pH 7.0) at a scan rate of 50 mV/s. The electron
      transfer coefficient (alpha) and the standard rate constant of the surface
      reaction (Ks) of cytochrome c on DNA-modified electrodes could be estimated to be
      0.87 and 34.52 s(-1), respectively. The DNA-modified glassy carbon electrode
      could be applied to detect cytochrome c by means of differential pulse
      voltammetry (DPV). The cathodic peak current was proportional to the quantity of
      cytochrome c in the range of 4.0 x 10(-6) M to 1.2 x 10(-5) M. The correlation
      coefficient is 0.996, and with the detection limit was 1.0 x 10(-6) M (three
      times the ratio of signal to noise, S/N = 3).

PMID- 16896246
TI  - Determination of copper(II) by anodic stripping voltammetry at a 2,5-dimercapto
      1,3,4-thiadiazol self-assembled monolayer-based gold electrode.
AB  - 2,5-Dimercapto-1,3,4-thiadiazol (DMTD) can bind on the surface of a gold
      electrode through the strong gold-sulfur interaction. The fabrication and
      electrochemical characteristics of the DMTD self-assembled monolayer (SAM)
      modified gold electrode were investigated. The DMTD SAM electrode exhibited a
      significantly increased sensitivity. Cu(II) was accumulated in phosphate buffer
      (pH 4.6) at a potential of -0.6 V (vs. Ag/AgCl) for 40 s and then determined by
      anodic stripping voltammetry (ASV) in copper-free phosphate buffer (pH 5.0). The
      effects of various parameters, such as the pH values of the preconcentration
      solution and measurement solution, the accumulation potential, and the
      accumulation time, were investigated. Under the optimum conditions, a linear
      calibration graph was obtained in the concentration range of 8.0 x 10(-6) to 8.0
      x 10(-5) mol l(-1) with a correlation coefficient of 0.9978. The relative
      standard deviations for eight successive determinations were 4.3 and 2.9% for 1.0
      x 10(-5) and 2.0 x 10(-5) mol l(-1) Cu(II), respectively. The detection limit
      (three times signal to noise) was 4.0 x 10(-7) mol l(-1). The proposed
      voltammetric method was utilized successfully to detect the concentration of
      Cu(II) ions in tap water samples.

PMID- 16896247
TI  - Spectrophotometric determination of arsenic in water samples based on micro
      particle formation of ethyl violet-molybdoarsenate.
AB  - In this study, a simple and sensitive method for the determination of arsenic in
      water samples was developed. The method is based on the formation of micro
      particles of Ethyl Violet and molybdoarsenate, which gives an apparently
      homogeneous blue color to the solution. The absorption of the excess dye
      gradually decreases due to its conversion to a colorless carbinol species under
      strongly acidic conditions. Consequently, the sufficiently low reagent blank
      enables the spectrophotometric determination of arsenic with the detection limit
      of 4 microg l(-1). The coefficient of variation for the spectrophotometry at 50
      microg l(-1) was 3.5% (n = 5). Furthermore, it is possible to detect
      concentrations as low as 10 microg l(-1) of arsenic visually. Our method will be
      useful as a simple, rapid, and cost-effective field test of arsenic, requiring no
      complex apparatus or skilled laboratory support.

PMID- 16896248
TI  - A calibration method for measurement of small alkyl organic peroxy radicals by
      chemical amplifier.
AB  - A new method is proposed to determine the calibration factor (CF) of methyl and
      ethyl peroxy radicals in a chemical amplifier. The radical source comes from the
      reactions of excess methane and ethane, respectively, with known concentrations
      of OH radicals generated by the photolysis of water vapor at 184.9 nm in air in a
      flow tube. This yields a mixed radical source with equal amounts of HO2 and RO2
      (R = CH3, C2H5). The CF for RO2 can be derived from the CF for HO2 and an average
      CF for the mixed radicals. The reliability of the method was evaluated by
      comparing the CF ratios of RO2 to HO2 obtained from both the experiments and
      theoretical calculations.

PMID- 16896249
TI  - Flow-injection determination of thyroxine using immobilized enzyme with tris(2,2'
      bipyridyl)ruthenium(III) chemiluminescence detection.
AB  - A flow-injection method is reported for the determination of thyroxine based on
      its enhancement effect on the tris(2,2'-bipyridyl)ruthenium(III)
      chemiluminescence reaction in the presence of NADH using immobilized alcohol
      dehydrogenase purified from baker yeast. The limit of detection (3 sigma blank)
      was 5.0 x 10(-8) M with a sample throughput of 80 h(-1). The calibration graph
      was linear over the range 0.5 - 10 x 10(-7) M (r2= 0.9988) with the relative
      standard deviation in the range 1.4 - 3.5% (n = 4). The effect of common
      excipients used in pharmaceutical preparations, some organic compounds and metal
      ions was studied. The method was applied to pharmaceutical thyroxine tablets, and
      the obtained results were not significantly different from the amount quoted.

PMID- 16896250
TI  - Preparation of the capillary-based microchips for solid phase extraction by using
      the monolithic frits prepared by UV-initiated polymerization.
AB  - A microfluidic solid phase extraction (SPE) array for sample enrichment was
      prepared by a simple method, a hot embossing technique. Five fused-silica
      capillaries (250 microm i.d., 380 microm o.d.) were partly embedded parallel in a
      polymethyl methacrylate (PMMA) microchip to serve as the extraction channels.
      Within each of the channels, a 2-mm-long monolithic porous polymer was prepared
      by in-situ photoinitiated polymerization. This then acted as the frit for packing
      of the extraction materials (octadecylsilica beads, ODS). By defining the light
      exposure window on the channels, one can easily control the length and location
      of the polymer frits and the ODS beads can be packed at the desired location.
      With this method, solid phase extraction channels for microfluidic use can be
      easily prepared without complex fabrication of microstructures. Several SPE
      channels can be conveniently made in one microchip since the frits can be
      prepared in different channels through one polymerization; packing of the
      different channels can also be performed simultaneously. With the use of dilute
      ephedrine solutions, the sample loading capacity, linearity, and reproducibility
      were characterized. Coupled with the fast capillary electrophoresis separation,
      this microchip SPE array was applied for the detection of ephedrines in human
      urine.

PMID- 16896251
TI  - Extraction of metal ions using chemically modified silica gel covalently bonded
      with 4,4'-diaminodiphenylether and 4,4'-diaminodiphenylsulfone-salicylaldehyde
      Schiff bases.
AB  - Two new chelating materials (Si-DDE-o-HB, and Si-DDS-o-HB) were synthesized by
      modifying the activated silica gel phase with Schiff bases of 4,4'
      diaminodiphenylether (DDE)/4,4'-diaminodiphenylsulfone (DDS) and o
      hydroxybenzaldehyde (o-HB). The synthesized materials were characterized by FTIR
      and BET surface area measurement techniques. The extraction of metal ions such as
      Zn2+, Mn2+ and Cr3+ by the chelating material Si-DDE-o-HB was found to be higher
      than that by Si-DDS-o-HB. The order of metal sorption was found to be Zn2+ > Mn2+
      > Cr3+. The correlation coefficients for Freundlich and Langmuir adsorption
      isotherms were compared for the sorption of Zn2+ onto the chelating material. The
      loading and elution of the metal ion solution was examined at optimum pH 7.5 and
      0.5 cm3 min-1 flow rate of the solution using a column technique. The
      preconcentration factor for the elution of Zn2+ using dilute HNO3 was found to be
      66.2 with a breakthrough volume of 15 cm3. The data obtained for the
      preconcentration of Zn2+ by the column technique suggested that the material Si
      DDE-o-HB can find industrial applications.

PMID- 16896252
TI  - Chemometric classification of traditional Chinese medicines by their geographical
      origins using near-infrared reflectance spectra.
AB  - Some raw materials that have different places of production for the plant sources
      of the drugs Astragalus membranaceus and ginseng have been studied, based on
      their near-infrared reflectance spectra. The experimentally recorded spectra
      represent heavily ill-posed and highly correlative data sets. Three related
      methods, i.e. the Fisher linear discriminant analysis (FLDA), the ridge-type
      linear discriminant analysis (RLDA) and a newly proposed penalized ridge-type
      linear discriminant analysis (PRLDA), have been investigated. FLDA over-fits for
      the training objects of the two data sets to a high extent and is unstable for
      the predictive objects of the two data sets. RLDA shows obvious improvement in
      terms of over-fitting and unstability, but the stability for the predictive
      objects of the two data sets is too sensitive to their ridge-type penalized
      weights, tending to produce erroneous discrimination results. The proposed PRLDA
      can circumvent the two aforementioned problems with a large domain of penalized
      weights for correct discriminant analysis of the two data sets studied. The
      combination of the PRLDA method and near infrared reflectance spectroscopy can be
      adapted for the discrimination of the production places of plant sources of these
      drugs.

PMID- 16896253
TI  - Multilayered assemblies composed of brilliant yellow and poly(allylamine) for an
      optical pH sensor.
AB  - Multilayered thin films containing poly(allylamine) (PAA) and brilliant yellow
      (BY) were prepared on a quartz slide by a layer-by-layer (LBL) deposition
      technique. The UV-visible spectra of the PAA/BY films were sufficiently changed
      depending upon the pH value of the solution in which the film was immersed. The
      response of the PAA/BY films was very fast (within a second) upon pH change from
      9.0 to 5.0, while the response time was ca. 100 s upon pH change from 5.0 to 9.0.

PMID- 16896254
TI  - Influence of AgCl precipitates on the precipitation titration of sodium chloride
      by constant-current coulometry.
AB  - The precipitation titration of sodium chloride with electrogenerated silver ion
      was studied. The production of a precipitate of silver chloride had a significant
      effect on the titration results because the precipitate involved unreacted
      chloride or unreacted silver ion. The accuracy of the method was investigated by
      changing the introduction time of a sodium chloride solution to the coulometric
      cell during the process of electrolysis, and examining the dependency on the
      sample size. The accuracy of the measurement of the precipitation titration is
      discussed.

PMID- 16896255
TI  - Borate cross-linked/total rhamnogalacturonan II ratio in cell walls for the
      biochemical diagnosis of boron deficiency in hydroponically grown pumpkin.
AB  - Boron (B) is an essential micronutrient for vascular plants. The function of B
      has been demonstrated to cross-link monomeric rhamnogalacturonan II (mRG-II) to
      form dimeric RG-II-borate (dRG-II-B), and thus to stabilize plant cell walls. The
      dRG-II-B to total RG-II ratio in the cell walls of pumpkin hydroponically grown
      under various low-B conditions was analyzed to evaluate its applicability to the
      diagnosis of plant B deficiency. The dRG-II-B ratio in cell walls ranged between
      approximately 0.9 in B-sufficient tissues and approximately 0.15 in severe B
      deficient tissues, reflecting the B nutritional status of tissues. This result
      indicates that the degree of B shortage in plant tissues is very likely to be
      diagnosed by the dRG-II-B ratio in cell walls.

PMID- 16896256
TI  - Determination of ammonium cations and alkali and alkaline earth metal cations in
      jellyfish by capillary zone electrophoresis.
AB  - We developed a capillary zone electrophoresis method with indirect UV detection
      for determination of ammonium cations and alkali and alkaline earth metal cations
      in jellyfish. As the background electrolyte, a mixture of N-methylbenzylamine,
      citrate, and 18-crown-6 was used for the complete separation of all analyte
      cations. The limits of detection were 0.13 - 0.34 mg l(-1) at a signal-to-noise
      ratio of three. The values of the relative standard deviation of peak area were
      3.2 - 4.9%. The proposed method successfully determined the above analyte cations
      in jellyfish for approximately 4 min.

PMID- 16896257
TI  - Optically specific detection of D- and L-lactic acids by a flow-injection dual
      biosensor system with on-line microdialysis sampling.
AB  - A flow-injection dual biosensor system with microdialysis sampling is proposed
      for the simultaneous determination of D-lactic and L-lactic acids. The dialysate
      from the microdialysis tube is delivered to a sample loop of the six-way
      autoinjector and then automatically injected into the flow-injection line with a
      dual enzyme electrode arranged in perpendicular to the flow direction. The dual
      enzyme electrode is constructed by hybridizing a poly(1,2-diaminobenzene) film
      into two sensing parts which respond selectively to D-lactic and L-lactic acids,
      respectively, without any cross-reactivity. The proposed flow-injection analysis
      method can be successfully applied to the simultaneous determination of D,L
      lactic acids in alcoholic beverages.

PMID- 16896258
TI  - Determination of fructosyl amino acids and fructosyl peptides in protease
      digested blood sample by a flow-injection system with an enzyme reactor.
AB  - A flow-injection system with an enzyme reactor was proposed for the measurement
      of fructosyl amino acids and fructosyl peptides in protease-digested blood
      samples. A fructosyl-amino acid oxidase (FAOX-TE) and two fructosyl-peptide
      oxidases (FPOX-CE and FPOX-CET) were covalently immobilized onto an inert
      support. They were used as the enzyme reactor in a FIA system with a hydrogen
      peroxide electrode. In particular, the FPOX-CET reactor possessed high
      selectivity for the detection of fructosyl valine (FV) and fructosyl valyl
      histidine (FVH) and an excellent operational stability. The proposed FIA system
      with the FPOX-CET reactor responded linearly to the concentration of FV over the
      dynamic range of 7.8 x 10(-6) to 5.8 x 10(-4) M. The present method could be
      successfully applied to the assay of FV and FVH in the protease-digested blood
      samples.

PMID- 16896259
TI  - Flow-injection chemiluminescence determination of ofloxacin and levofloxacin in
      pharmaceutical preparations and biological fluids.
AB  - A novel, rapid and sensitive analytical method is described for determination of
      ofloxacin and levofloxacin by enhanced chemiluminescence (CL) with flow-injection
      sampling. The method is based on the CL reaction of the Ce(IV)-Na2S2O4
      ofloxacin/levofloxacin-H2SO2 system. The enhanced CL mechanism was developed and
      the optimum conditions for CL emission were investigated. The CL intensity was
      correlated linearly (r = 0.9988) with the concentration of ofloxacin (or
      levofloxacin) in the range of 1.0 x 10(-8) - 1.0 x 10(-7) g ml(-1) and 1.0 x 10(
      7) - 6.0 x 10(-6) g ml(-1). The detection limit (S/N = 3) is 7 x 10(-9) g ml(-1).
      The relative standard derivation (RSD, n = 11) is 2.0% for ofloxacin at 4 x 10(
      7) g ml(-1) and for levofloxacin at 6 x 10(-7) g ml(-1). This method has been
      successfully applied for the determination of ofloxacin and levofloxacin in
      pharmaceutical preparations and biological fluids with satisfactory results.

PMID- 16896262
TI  - A case of type 2 diabetes mellitus in an elderly patient with rapid attenuation
      of insulin secretion that resembled fulminant type 1 DM but with incomplete beta
      cell damage.
AB  - We recently encountered a 66-year-old Japanese man who had suffered from acute
      hyperglycemia following flu-like symptoms during treatment of type 2 diabetes.
      Despite significantly increased plasma glucose levels, HbA1c was only slightly
      elevated. The possibility of autoimmune type 1 diabetes was excluded because of
      negative islet-related autoantibodies. Serum levels of pancreatic exocrine
      enzymes, amylase, lipase, and elastase-l were elevated. However, the insulin
      secreting function of his islets was not severely damaged. This case is
      particularly notable for two reasons. First, it showed a fulminant type 1
      diabetes-like clinical onset, but his beta cell function was fairly preserved.
      Second, it developed during the treatment of type 2 diabetes in an elderly
      patient.

PMID- 16896263
TI  - Frequent, aggressive behaviors of thyroid microcarcinomas in korean patients.
AB  - The incidence of thyroid microcarcinoma is rising due to the frequent use and
      improvement of fine-needle aspiration biopsy and ultrasonography. Since the
      recent update of the TNM (Tumor, Node, Metastasis) staging system for thyroid
      cancer, the importance of lymph node metastasis became more prominent. In the
      present study, we evaluated the prognostic factors and extension of thyroid
      microcarcinomas in Korean patients. The clinical and pathological findings in
      patients with thyroid microcarcinomas in a Korean hospital from January through
      December 2004 were evaluated. A total of 302 (50.2%) out of 601 cases of thyroid
      cancers were microcarcinomas. Evaluation of the histology revealed that nearly
      all of the cases (300 of 302) were of the papillary type. Analyzing patients of
      papillary thyroid microcarcinomas, 273 (91.0%) out of 300 patients of papillary
      microcarcinomas were women. Seventy-eight (26.0%) cases contained multiple tumor
      masses (> or =2), including 49 (16.3%) cases that were bilateral. There were 84
      (28.0%) cases of extrathyroidal extensions and 89 cases (29.7%) of lymph node
      metastasis, but no cases of distant metastases. Application of the new staging
      system revealed 7 (2.3%) cases that changed from stage III to stage IVA. Thyroid
      microcarcinomas were also associated with poor prognostic factors and appear to
      exist at relatively higher cancer stages. Therefore, it is important to treat
      them as early and as vigorously as possible with extensive surgery, radioactive
      iodine therapy, and thyroxine suppression.

PMID- 16896264
TI  - Manifestation of rheumatoid arthritis after transsphenoidal surgery in a patient
      with acromegaly.
AB  - Acromegalic arthropathy is one of the most frequent manifestations occurring in
      acromegaly patients. In contrast, rheumatoid arthritis (RA) is a rare clinical
      complication in acromegaly patients. Here, we report a 70-year-old Japanese woman
      with acromegaly, who complained of bilateral finger stiffness and polyarthralgia
      two months after transsphenoidal surgery of a growth hormone (GH)-secreting
      pituitary adenoma. Postoperative levels of serum GH and insulin-like growth
      factor-1 (IGF-1) were markedly decreased without any secretory deficiency of
      other anterior pituitary hormones. Hand X-ray did not show typical RA changes;
      however, erosive changes in carpal bones were clearly detected by magnetic
      resonance imaging with gadolinium enhancement. Based on the levels of serological
      markers in the patient following surgery including C-reactive protein, rheumatoid
      factor and matrix metalloproteinase-3, anti-rheumatic therapy was subsequently
      commenced. Regardless of the levels of GH and IGF-1, acromegaly patients
      frequently complain about joint-related symptoms even after remission. Therefore,
      careful observation of bone erosive changes and immunological activity in
      acromegaly patients is required when joint-related symptoms persist.

PMID- 16896265
TI  - No evidence of ARAF, CRAF and MET mutations in BRAFT1799A negative human
      papillary thyroid carcinoma.
AB  - The MAPK signaling pathway plays a crucial role in tumorgenesis and cell
      proliferation in human papillary thyroid carcinoma (PTC). Ret/PTC rearrangements,
      RAS and BRAF mutations, the main non-overlapping genetic alterations all leading
      to MAPK cascade activation, are cumulatively identified in 60-80% of PTCs. In
      approximately one-fourth of the cases, oncogenic background potentially
      contributing to MAPK activation in PTC might be different. We therefore attempted
      to evaluate the mutational status of genes encoding other members of RAF family
      known to act upstream of MAPKs, ARAF and CRAF (RAF-1). In addition we also
      analyzed the MET gene that encodes hepatocyte growth factor/scatter factor
      receptor overexpressed in most of PTCs and a MAPK cascade contributor. In 129
      Japanese patients with PTC, BRAF(T1799A) was detected in 65 cases (50.4%), and
      the remaining 64 tumor specimens were subjected to mutation analysis of kinase
      domains of ARAF, CRAF and MET genes, and hotspots of K- and N-RAS genes. No ARAF,
      CRAF, MET, K- and N-RAS mutations were revealed. Based on these observations, we
      concluded that despite the fact that ARAF, CRAF and MET are actively expressed,
      alterations of these genes are rare in PTC and unlikely to play a perceptible
      role in the molecular pathogenesis of this type of human malignancy.

PMID- 16896266
TI  - A case of preclinical Cushing's syndrome associated with diurnal rhythms of ACTH
      and cortisol in blood: correlation with histological findings.
AB  - We describe a case of adrenocortical adenoma with preclinical Cushing's syndrome
      demonstrating diurnal rhythms of ACTH and cortisol in blood. A 50-year-old man
      was admitted to the hospital for the evaluation of incidental right adrenal mass
      with hyperglycemia and hypertension. On admission, there were no signs of
      clinical manifestation of hypercortisolism. The basal levels of cortisol (9.3
      microg/dl) and ACTH (9.4 pg/ml) at 0800 h were not elevated and these diurnal
      rhythms were maintained. One or 8 mg of dexamethasone given orally overnight
      suppressed the plasma ACTH but not serum cortisol. Ultrasonogram, CT and
      scintiscan of (131)I adosterol all demonstrated an enlarged adrenal mass in the
      right adrenal gland. The right adrenal gland was subsequently resected by
      laparoscopic surgery. Histopathological findings of resected adrenal tumor were
      consistent with adrenocortical adenoma. Adjacent non-neoplastic adrenal tissue
      demonstrated adrenocortical atrophy but DHEA-sulfotransferase immunoreactivity in
      the zona reticularis was detected.

PMID- 16896267
TI  - Two-day thionamide withdrawal prior to radioiodine uptake sufficiently increases
      uptake and does not exacerbate hyperthyroidism compared to 7-day withdrawal in
      Graves' disease.
AB  - The appropriate period of antithyroid drug (ATD) discontinuation before
      radioiodine therapy is the most critical problem in Graves' disease patients
      under going treatment with ATD. To determine the optimal period that does not
      alter the outcome of radioiodine therapy or exacerbate hyperthyroidism, we
      compared serum FT4 levels at radioiodine uptake (RAIU) and therapy outcomes
      between a 2-day withdrawal group and 7-day withdrawal group. We prospectively
      recruited 43 patients for the 2-day withdrawal protocol and retrospectively
      reviewed 49 patients treated with radioiodine following the protocol of 7-day
      withdrawal. There was no significant difference in RAIU between the 2 groups. The
      mean serum FT4 level measured on the first day of 24-h RAIU of the 7-day group
      was significantly higher than that in the 2-day group. There were no significant
      differences in the outcomes at each point (6 months, 1 year, and 2 years after
      therapy) between the 2 groups. Our results indicated that withdrawal of ATD for 2
      days is superior to 7 days in that 2 days discontinuation did not exacerbate
      hyperthyroidism. In order to prevent serum thyroid hormone increase after ATD
      withdrawal and radioiodine therapy, a 2-day ATD withdrawal period before
      radioiodine therapy may be useful for high-risk patients such as the elderly and
      patients with cardiac complications. We believe that the 2-day ATD withdrawal
      method may be useful for patients undergoing treatment with ATD who are to
      undergo radioiodine therapy.

PMID- 16896268
TI  - Longitudinal study of patients with idiopathic isolated TSH deficiency: possible
      progression of pituitary dysfunction in lymphocytic adenohypophysitis.
AB  - The relationship between isolated TSH deficiency and hypophysitis was studied.
      Six patients (five women and one man) with idiopathic isolated TSH deficiency
      were longitudinally investigated with an interval of 31 to 60 months. Clinical
      symptoms, laboratory results and endocrine function were investigated as well as
      pituitary magnetic resonance imaging (MRI) at the start and the end of the study.
      Clinically, initial symptoms due to hypothyroidism were ameliorated by the
      thyroid hormone replacement in all patients. Oligomenorrhea newly appeared during
      the study in three patients, although no other symptoms appeared. Serum fT3 and
      fT4 levels were within the reference ranges, and serum TSH level and its response
      to TRH stimulation remained low in all patients. Peak plasma GH level during GRH
      stimulation was significantly (p<0.03) decreased, at the end of the study as
      compared with the start. Peak plasma FSH level to LHRH stimulation was
      significantly (p<0.03) decreased as well as basal FSH level. In contrast, peak of
      prolactin during TRH stimulation was significantly (p<0.03) increased at the end
      of the study as compared with the start as well as basal prolactin level.
      Endocrine features at the end of the study were compatible with those of
      lymphocytic adenohypophysitis (LAH). MRI of the pituitary gland showed empty
      sella in one patient and slight swelling in two patients. These findings remained
      unchanged during the study period. One patient underwent pituitary biopsy, with
      histological examination showing atypical form of LAH. LAH can cause idiopathic
      isolated TSH deficiency and can functionally progress to combine dysfunction of
      the pituitary gland.

PMID- 16896269
TI  - Chronic kidney disease and the cardiometabolic syndrome.

PMID- 16896270
TI  - Elevated endothelin-1 levels are associated with decreased arterial elasticity in
      hypertensive patients.
AB  - Endothelin-1 stimulates collagen synthesis and is increased in hypertension, but
      its effect on collagen degradation remains unknown. The current study tested the
      hypothesis that elevated endothelin-1 levels are associated with decreased
      collagenase activity, markers of collagen degradation, and arterial compliance in
      hypertensive patients. Normotensive (n = 10) and hypertensive (n = 13) patients
      who were not on any antihypertensive medication were recruited, and small and
      large artery elasticity index, systemic vascular resistance, pulse pressure, and
      blood pressure were determined using blood pressure waveform analysis. Large
      artery elasticity index and collagen degradation products were decreased whereas
      endothelin-1, systemic vascular resistance, and pulse pressure were elevated in
      hypertensive patients. Plasma endothelin-1 was negatively correlated with a cross
      linked C-terminal telopeptide of collagen type I, a collagen degradation marker
      (r = -0.43; p = 0.04), collagenase matrix metalloproteinase-1 (r = -0.48; p =
      0.02), and large artery elasticity (r = -0.45; p = 0.03) and positively
      correlated with pulse pressure (r = 0.68; p = 0.0005). These results suggest that
      endothelin-1 contributes to decreased arterial compliance in hypertension via
      inhibition of collagen degradation.

PMID- 16896271
TI  - Continuous improvement of arterial compliance beyond blood pressure decrease
      after 5 years of antihypertensive treatment.
AB  - Pulse wave velocity is a reliable marker of arterial compliance. Stiffness of
      large and elastic arteries leads to a faster propagation of pulse wave. The aim
      of this study was to evaluate changes in arterial distensibility using
      antihypertensive drugs. This treatment focused on the inhibition of the renin
      angiotensin-aldosterone system and the changes produced in blood pressure.
      Measurements were taken at baseline and throughout 60 months in 66 previously
      untreated hypertensive patients (22 men and 44 women, aged 54 +/- 9.5 years,
      range 38-73 years at baseline). All patients received either angiotensin
      converting enzyme inhibitors or, in case of adverse effects, angiotensin receptor
      blockers. To control blood pressure, diuretics, calcium channel blocking agents,
      or beta blockers were added when appropriate. Statistical analysis was performed
      by means of ANOVA with alpha = 0.05. Systolic and diastolic blood pressure
      decreased during the first year without significant changes thereafter. There
      were no significant changes in pulse pressure. Pulse wave velocity showed a
      continuous and significant decrease throughout the follow-up period, but its
      reduction since the third year was more evident than the decrease in systolic and
      diastolic blood pressure (p < 0.0001 for both). This observation could be related
      to changes in arterial remodeling probably due to angiotensin-converting enzyme
      inhibition or renin angiotensin system blockade. Further investigations are
      needed to establish this relationship.

PMID- 16896272
TI  - Prevalence of the metabolic syndrome in the United States National Health and
      Nutrition Examination Survey 1999-2002 according to different defining criteria.
AB  - The authors studied the prevalence of the metabolic syndrome in the 1999-2002
      National Health and Nutrition Examination Survey (NHANES) according to the World
      Health Organization, National Cholesterol Education Program (NCEP), and
      International Diabetes Federation (IDF) definitions. There was 92.9% agreement
      between the NCEP and IDF definitions. The IDF prevalence was higher (p = 0.001)
      due to more men fulfilling its criteria than the NCEP's (39.9 +/- 1.7% vs. 33.6
      +/- 1.6%; p = 0.007). If central obesity were not a prerequisite, the IDF
      prevalence would increase slightly to 40.3 +/- 1.1%. Subjects categorized as
      having the metabolic syndrome under IDF but not NCEP tended to be men, younger,
      and leaner. Their prevalence of self-reported coronary heart disease was not
      significantly different from that of other metabolic syndrome patients. Whether
      waist circumference is a prerequisite does not affect the diagnosis of the
      metabolic syndrome in the United States. The IDF definition identifies additional
      individuals at risk for cardiovascular disease.

PMID- 16896273
TI  - Efficacy and safety of coadministered amlodipine and atorvastatin in patients
      with hypertension and dyslipidemia: results of the AVALON trial.
AB  - The AVALON study was a randomized, multicenter trial to assess the efficacy and
      safety of coadministered amlodipine and atorvastatin in patients with
      hypertension and dyslipidemia. Phase one was an 8-week, double-blind, double
      dummy, placebo-controlled period whereby patients received amlodipine 5 mg,
      atorvastatin 10 mg, amlodipine 5 mg and atorvastatin 10 mg, or placebo.
      Thereafter, all patients received single-blind amlodipine 5 mg and atorvastatin
      10 mg for 8-weeks, followed by 12 weeks of open-label treatment where doses could
      be titrated to improve low-density lipoprotein cholesterol and blood pressure
      control. A total of 847 patients entered the double-blind phase. At Week 8, 45%
      of the patients receiving amlodipine 5 mg and atorvastatin 10 mg reached both
      their blood pressure and low-density lipoprotein cholesterol goals, compared with
      8.3% with amlodipine (p < 0.001), 28.6% with atorvastatin (p < 0.001), and 3.5%
      with placebo. At 28 weeks, 67.1% of patients coadministered amlodipine and
      atorvastatin (mean doses, 7.6 mg and 28.4 mg, respectively) achieved both
      targets. Framingham estimated 10-year risk of coronary heart disease declined
      from baseline levels of 15.1% to 6.9% at Week 28. Following coadministered
      treatment, the adverse events reported were similar to either agent alone.
      Concomitant administration of amlodipine and atorvastatin is an effective and
      well tolerated treatment for coexisting hypertension and dyslipidemia.

PMID- 16896274
TI  - Early morning blood pressure surge.
AB  - Alterations in the circadian rhythm of blood pressure, whether a loss of the
      nighttime dip or an exaggeration of the early morning increase that occurs upon
      rising, indicate increased cardiovascular risk. Estimates of the magnitude of the
      blood pressure surge on rising vary depending on technique and population, but it
      is usually around 10-30 mm Hg systolic and 7-23 mm Hg diastolic. The magnitude of
      the surge increases with age, alcohol consumption, and smoking and is greater in
      whites. Blood pressure variations and morning plasma aldosterone are closely
      correlated. A high morning surge is linked to increased target organ damage as
      well as strokes and other cardiovascular complications. Therapeutic options exist
      to reduce the magnitude of the morning blood pressure surge-notably, the use of
      drugs with a long duration of action, the use of medications that specifically
      antagonize the morning surge (such as alpha blockers), and the administration of
      drugs upon awakening but before rising.

PMID- 16896275
TI  - Regression of alterations in retinal microcirculation following treatment for
      arterial hypertension.
AB  - Evaluation of early hypertension-related alterations in retinal microcirculation
      has been subjective and poorly reproducible. The authors recently described a
      semiautomatic computerized system for evaluation of the calibre of retinal blood
      vessels that has shown very good reproducibility. In the study, this system was
      used to measure the calibres of retinal arterioles and veins, and their ratio, in
      a group of 51 hypertensive outpatients before and after 6 months of treatment
      with losartan or, if required for satisfactory blood pressure control, losartan
      plus hydrochlorothiazide. Mean retinal arteriole diameter increased from 0.0842
      +/- 0.003 mm to 0.0847 +/- 0.003 mm (p = 0.001). Arteriovenous ratio increased
      from 0.753 +/- 0.03 to 0.756 +/- 0.03 (p = 0.005). This observation suggests
      regression of early hypertension-related alterations in retinal microcirculation
      after 6 months of antihypertensive treatment.

PMID- 16896276
TI  - Hyperthyroidism: a secondary cause of isolated systolic hypertension.
AB  - Isolated systolic hypertension is the most common form of hypertension,
      especially among patients 50 years or older. What is not appreciated is that
      there are secondary causes of isolated systolic hypertension. Hyperthyroidism
      increases systolic blood pressure by decreasing systemic vascular resistance,
      increasing heart rate, and raising cardiac output. Potential cardiovascular
      consequences of hyperthyroidism include atrial arrhythmias (especially atrial
      fibrillation), pulmonary hypertension, left ventricular hypertrophy, and heart
      failure. The prevalence of hypertension is greater among hyperthyroid patients
      than euthyroid patients. Whether there is a blunted nocturnal decline in
      ambulatory blood pressure among hyperthyroid patients is more controversial.
      Treatment is associated with a reduction in systolic blood pressure, heart rate,
      and cardiac output.

PMID- 16896277
TI  - Following up angiotensin-converting enzyme inhibitor monotherapy.

PMID- 16896281
TI  - B cell receptor signaling in human systemic lupus erythematosus.
AB  - PURPOSE OF REVIEW: The purpose of this review is to inform the scientific
      community of the most recent findings surrounding B cell receptor signaling
      function in human systemic lupus erythematosus and how altered B cell signaling
      may explain the characteristic hyperactivity of B cells in active disease and
      contribute to its pathogenesis. RECENT FINDINGS: B cell receptor signaling is
      abnormal in patients with active systemic lupus erythematosus as demonstrated by
      increased calcium flux and global B cell hyperactivity. Altered signaling has
      been explained by a variety of factors such as defective FcgammaRIIB signaling,
      decreased expression of the protein tyrosine kinase Lyn, and increased serum
      levels of B lymphocyte stimulator. SUMMARY: The studies reviewed suggest that B
      cells from systemic lupus erythematosus patients display molecular signaling
      defects that most likely contribute to pathogenesis of the disease and explain
      the characteristic hyperactivity of B cells in active disease.

PMID- 16896282
TI  - Sex and systemic lupus erythematosus: the role of the sex hormones estrogen and
      prolactin on the regulation of autoreactive B cells.
AB  - PURPOSE OF REVIEW: For many decades, it has been speculated that sex hormones
      play a role in systemic lupus erythematosus. Recent data accumulated during the
      past few years provide striking evidence that hormonal modulation of B cells can
      have a profound impact on the survival, maturation and repertoire selection of
      autoreactive B cells and begin to explain the sex bias associated with the
      condition. RECENT FINDINGS: While there are still insufficient clinical data to
      define a role for estrogen or prolactin in human systemic lupus erythematosus,
      recent studies of anti-DNA antibody transgenic mice clearly demonstrate that an
      elevation in either estrogen or prolactin breaks tolerance of high affinity DNA
      reactive B cells and induces a lupus phenotype. B cells with the same antigenic
      specificities are rescued by either estrogen or prolactin, but estrogen promotes
      the survival and activation of the T independent marginal zone B cell subset,
      while prolactin promotes the survival and activation of the T dependent
      follicular B cell subset. SUMMARY: Elevations in the levels of estrogen or
      prolactin can promote the survival and activation of high affinity autoreactive B
      cells. These hormones engage different B cell pathways to interfere with B cell
      tolerance. The identification of systemic lupus erythematosus patients with
      either an estrogen-responsive or prolactin-responsive disease will further the
      development of therapeutics that can specifically modulate hormonal responses.

PMID- 16896284
TI  - Pathogenesis and treatment of systemic lupus erythematosus nephritis.
AB  - PURPOSE OF REVIEW: Glomerulonephritis is a challenging complication of systemic
      lupus erythematosus that still results in kidney loss in up to 30% of patients.
      In this review we highlight the development of integrated efforts to link
      pathogenesis with disease definition and new therapeutics. RECENT FINDINGS:
      Immune complex deposition in the kidney initiates an inflammatory cascade that
      causes glomerular disease but there are many modulating factors including genetic
      predisposition, products of the innate immune system, cytokines, complement and
      activated cells (both renal and immune). Animal models can help dissect potential
      disease mechanisms but the study of multiple models will be required since there
      are multiple subsets of human disease. Recent therapeutic studies in humans
      address the distinction between therapies for remission induction and remission
      maintenance. Multiple studies confirm the therapeutic equivalence of
      mycophenolate mofetil and cyclophosphamide in induction of remission but results
      are still far from ideal. The next few years should see the testing of new
      biologic reagents in humans. Another area of interest is the search for
      noninvasive measures of disease and disease response. SUMMARY: Although there has
      been remarkable progress in our understanding of the immunology and phenotype of
      lupus nephritis current therapies have insufficient efficacy. As new therapies
      emerge, improved clinical design coupled with mechanistic studies will be needed
      to identify agents that may be effective only in some patient subpopulations.

PMID- 16896285
TI  - Clinical trial design in systemic lupus erythematosus.
AB  - PURPOSE OF REVIEW: The purpose of this review is to discuss the challenges
      inherent in the design of clinical trials for patients with systemic lupus
      erythematosus. RECENT FINDINGS: Recent years have witnessed a renewed interest in
      the conduct of systemic lupus erythematosus clinical trials. Three key design
      decisions play particularly critical roles in determining the fate of these
      trials: selection of the study population from among patients with very
      heterogeneous disease manifestations; selection of the treatment and control
      regimens; and selection of the primary endpoint. Four recent randomized,
      controlled trials dealt with these decisions in the context of a variety of
      interventions, including new biologic agents, hormonal therapies, and anti
      metabolites. These trials are informative about the implications of each
      approach. SUMMARY: Systemic lupus erythematosus investigators are faced with
      substantial trial design challenges because of the inherently complex nature of
      this disease. The hope is that lessons learned from prior and ongoing trials will
      inform future trial design such that the efficacy of new agents can be determined
      and new therapies will become available for patients with SLE.

PMID- 16896283
TI  - Epstein-Barr virus and systemic lupus erythematosus.
AB  - PURPOSE OF REVIEW: Systemic lupus erythematosus is a complex human disease likely
      influenced by a compilation of necessary, but not individually sufficient,
      features. Although many genetic and environmental factors are associated, this
      review will focus on the evolving evidence for key Epstein-Barr virus specific
      roles. RECENT FINDINGS: Recent studies have shown additional molecular mimicry
      mechanisms between early events in lupus autoimmunity and specific Epstein-Barr
      virus responses. In addition, several recent papers have demonstrated increased
      Epstein-Barr viral load, increased numbers of latently infected peripheral B
      cells, impaired functional T cell responses, and association of the presence of
      Epstein-Barr virus DNA in systemic lupus erythematosus patients compared with
      controls. Additional work has continued to show association of various aspects of
      Epstein-Barr virus serology with systemic lupus erythematosus and a recent paper
      outlines differences in the pediatric systemic lupus erythematosus humoral immune
      response to Epstein-Barr virus nuclear antigen-1 compared with matched controls.
      SUMMARY: This review will briefly outline the recent advances that show
      serologic, DNA, gene expression, viral load, T cell responses, humoral fine
      specificity, and molecular mimicry evidence for differences between systemic
      lupus erythematosus patients and controls and the impact that these findings have
      on understanding the role of Epstein-Barr virus in systemic lupus.

PMID- 16896287
TI  - Genomic progress in pediatric arthritis: recent work and future goals.
AB  - PURPOSE OF REVIEW: Pediatric arthritis is a heterogeneous group of chronic
      arthropathies that are influenced by complex genetic and perhaps environmental
      factors. Interacting genetic traits may one day be identified that provide the
      basis for predicting disease risk and other characteristics such as course, age
      of onset, and disease severity. The purpose of this review is to describe the
      recent progress towards identifying the multiple genes related to pediatric
      arthritis and understand how they relate to each other and to disease pathology.
      RECENT FINDINGS: Candidate gene studies are by far the most widely reported type
      of genetic studies to date for juvenile arthritis with only one genome-wide
      screen for juvenile rheumatoid/idiopathic arthritis published. Particular
      attention is paid to studies of candidate genes with potential immunological
      roles and those associated with other forms of autoimmunity. SUMMARY: Genomic
      studies may perhaps one day provide information to allow future classification
      systems of childhood arthritis to include molecular biomarkers as a complement to
      clinical observations, as well as understand how these genes or proteins relate
      to each other and to disease pathogenesis.

PMID- 16896288
TI  - Temporomandibular joint arthritis in juvenile idiopathic arthritis: the forgotten
      joint.
AB  - PURPOSE OF REVIEW: This review explores the prevalence, clinical and radiographic
      signs, and treatment of temporomandibular joint arthritis in children with
      juvenile idiopathic arthritis. RECENT FINDINGS: Temporomandibular joint arthritis
      seems to be a more frequent manifestation in patients with juvenile idiopathic
      arthritis than previously believed, in part due to the paucity of clinical
      symptoms and poor sensitivity of conventional radiographs used for diagnosis.
      Antinuclear antibody positivity, early onset of disease, and presence of systemic
      or polyarticular disease are all risk factors for temporomandibular joint
      arthritis but may underpredict temporomandibular joint involvement in juvenile
      idiopathic arthritis. Magnetic resonance imaging enhanced with gadolinium is
      currently the gold standard in detection of temporomandibular joint arthritis,
      and treatment with intra-articular corticosteroids has been shown to be effective
      and safe, with minimal side effects. SUMMARY: Given the paucity of clinical
      symptoms in temporomandibular joint arthritis, detection of temporomandibular
      joint inflammation using contrast-enhanced magnetic resonance imaging is
      essential for instituting appropriate therapy in a timely fashion. The use of
      intra-articular corticosteroids holds promise for control of temporomandibular
      joint inflammation and prevention of associated morbidities.

PMID- 16896289
TI  - Latest developments in the assessment and management of chronic musculoskeletal
      pain syndromes in children.
AB  - PURPOSE OF REVIEW: As many as 25% of new patients in pediatric rheumatology
      clinics present with idiopathic chronic pain and recent data suggest the
      prevalence of these conditions is increasing. Knowledge of the latest
      developments in assessment and treatment is critical for providing optimal
      clinical care. This review summarizes advances published in the past year
      forwarding our understanding of chronic musculoskeletal pain syndromes in
      children. RECENT FINDINGS: Research has recently focused on the impairment
      associated with chronic pain syndromes in children, issues impacting the
      diagnosis of these conditions, and the efficacy of pharmacological and
      psychosocial treatments. No diagnostic criteria have been developed for specific
      chronic pain syndromes in children; however, data from several studies
      substantiate the need for thorough assessment of the child and family in multiple
      domains. In addition, studies have expanded both pharmacologic and psychosocial
      treatment options for children with these syndromes. SUMMARY: Despite a growing
      body of research on chronic pain syndromes in children, there are no established
      standards of care. Data continues to support an interdisciplinary approach for
      effectively assessing and managing these conditions.

PMID- 16896290
TI  - Advances in the treatment of juvenile dermatomyositis.
AB  - PURPOSE OF REVIEW: Juvenile dermatomyositis is a rare chronic inflammatory
      disease that primarily affects the muscles and skin. Immunosuppressive therapy
      has played a very important role in reducing mortality rates and morbidity. The
      review focuses on the spectrum of medications currently used in the treatment of
      juvenile dermatomyositis, highlighting new advances and unanswered questions.
      RECENT FINDINGS: Data regarding the treatment of juvenile dermatomyositis come
      almost entirely from retrospective studies with relatively small numbers of
      patients. Corticosteroids continue to be the accepted first-line therapy.
      Evidence that the addition of methotrexate at initiation of treatment allows
      corticosteroids to be tapered more rapidly with good outcomes exists. High-risk,
      refractory patients may benefit from intravenous cyclophosphamide. Results in
      refractory patients treated with rituximab are also encouraging. Topical
      immunosuppressant agents have been largely disappointing in treating rash. The
      effect and role of exercise in the treatment and rehabilitation of patients with
      juvenile dermatomyositis is an interesting new area of research. SUMMARY: Future
      research in the treatment of juvenile dermatomyositis should focus on improving
      the understanding of disease course and its predictors such that treatment
      protocols can be developed to provide the most benefit and least amount of
      medication toxicity for the individual patient.

PMID- 16896291
TI  - Recognition and treatment of juvenile-onset spondyloarthritis.
AB  - PURPOSE OF REVIEW: The purpose of this review is to discuss the classification,
      diagnosis and management of juvenile-onset spondyloarthritis. RECENT FINDINGS:
      There have been changes in the classification criteria for juvenile-onset
      spondyloarthritis and magnetic resonance imaging has allowed for earlier
      detection of disease. Additionally, tumor necrosis factor-alpha blockers have
      been shown to be effective in the treatment of ankylosing spondylitis. There is
      evidence to suggest that early treatment may lead to better response. A high
      percentage of patients with enthesitis-related arthritis progress to develop
      ankylosing spondylitis within 10 years after presentation. Patients with juvenile
      onset ankylosing spondylitis appear to have poorer functional outcomes. SUMMARY:
      Juvenile-onset spondyloarthritis has variable clinical features that may lead to
      significant impairments. Improved classification criteria exist, but better
      techniques that are more sensitive are needed to diagnose disease earlier. New
      therapies appear to improve outcomes, but randomized controlled trials are needed
      in this population of patients.

PMID- 16896292
TI  - Research in osteoarthritis.

PMID- 16896294
TI  - Unloading joints to treat osteoarthritis, including joint distraction.
AB  - PURPOSE OF REVIEW: Patients are increasingly becoming interested in
      nonpharmacologic approaches to manage their osteoarthritis. This review examines
      the recent literature on the potential beneficial effects of unloading joints in
      the treatment of osteoarthritis, with a focus on joint distraction. RECENT
      FINDINGS: Mechanical factors are involved in the development and progression of
      osteoarthritis. If "loading" is a major cause in development and progression of
      osteoarthritis, then "unloading" may be able to prevent progression. There is
      evidence that unloading may be effective in reducing pain and slowing down
      structural damage. This review describes unloading by footwear and bracing
      (nonsurgical), unloading by osteotomy (surgical), and has a focus on unloading by
      joint distraction. Excellent reviews in all these three fields have been
      published over the past few years. Recent studies argue for the usefulness of a
      biomechanical approach to improve function and possibly reduce disease
      progression in osteoarthritis. SUMMARY: To improve patient function and possibly
      reduce disease progression, a biomechanical approach should be considered in
      treating patients with osteoarthritis. Further research (appropriate high-quality
      clinical trials) and analysis (clinical as well as preclinical and fundamental)
      are still necessary, however, to understand, validate, and refine the different
      approaches of unloading to treat osteoarthritis.

PMID- 16896293
TI  - The role of ambulatory mechanics in the initiation and progression of knee
      osteoarthritis.
AB  - PURPOSE OF REVIEW: This review examines recent in-vivo studies of ambulation and
      discusses the fundamental role of mechanics of ambulation in the initiation and
      progression of osteoarthritis at the knee. RECENT FINDINGS: Recent studies have
      supported earlier findings that a high adduction moment at the knee during
      ambulation was most frequently reported to influence the progression of medial
      compartment osteoarthritis. In contrast to previous findings in patients with
      osteoarthritis, recent work on healthy subjects reports that cartilage thickness
      increases with high ambulatory loads. Kinematic changes were associated with the
      initiation of osteoarthritis. Recent studies of subjects with high risk factors
      for knee osteoarthritis (obesity and anterior cruciate ligament injury) reported
      a relationship between kinematic changes during ambulation and the initiation of
      osteoarthritis at the knee. This review also contrasts the relative influence on
      osteoarthritis of knee mechanics measured during ambulatory and nonambulatory
      activities. SUMMARY: The initiation of osteoarthritis occurs when healthy
      cartilage experiences some condition (traumatic or chronic) that causes kinematic
      changes during ambulation at the knee to shift the load-bearing contact location
      of the joint to a region not conditioned to the new loading. The rate of
      progression of osteoarthritis is associated with increased load during
      ambulation.

PMID- 16896295
TI  - Who, when, and why total joint replacement surgery? The patient's perspective.
AB  - PURPOSE OF REVIEW: Although total joint replacement is an effective treatment for
      advanced arthritis, many whom might benefit are unwilling to consider this
      procedure. This review highlights advances in understanding of patients'
      perceptions of total joint replacement. RECENT FINDINGS: Research shows that
      patients' willingness to consider total joint replacement varies by sex,
      race/ethnicity, and socioeconomic status as a result of systematic differences in
      knowledge and beliefs about the procedure. Individuals with low socioeconomic
      status and minorities view the procedure less favorably than their wealthier,
      white counterparts, possibly partly explaining disparity in rates of use of the
      procedure among these groups. Among those undergoing total joint replacement, up
      to 30% experience a suboptimal outcome or are dissatisfied with results. Early
      work suggests that patients' expectations and self-efficacy are important
      potential predictors of postoperative outcome. Patient information needs
      regarding total joint replacement vary significantly and possibly systematically
      by sex and race/ethnicity. Available information materials may not address the
      concerns of many individuals contemplating the procedure, posing a potential
      barrier to surgery. SUMMARY: Targeted culturally sensitive knowledge
      dissemination strategies are needed to improve the knowledge and beliefs of
      people with hip/knee arthritis about total joint replacement.

PMID- 16896296
TI  - The assessment of disability associated with osteoarthritis.
AB  - PURPOSE OF REVIEW: Disability (activity limitation) is an important and common
      health outcome for patients with osteoarthritis, making accurate measures
      essential. This paper explores self-report measures of activity limitation
      associated with osteoarthritis and reports on recent conceptual advances that
      impact on the measurement of activity limitation. RECENT FINDINGS: The Western
      Ontario and McMaster Universities Osteoarthritis Index and the Short Form-36, the
      most commonly used measures to assess activity limitation, continue to be
      validated in osteoarthritis. There has been little consensus, however, about
      which measure to use across different types of osteoarthritis. While new measures
      have been developed to assess activity limitation, it remains unclear whether or
      not these are an improvement over existing measures. The International
      Classification of Functioning, Disability and Health is becoming an important
      consideration. Commonly used measures do not map directly onto individual
      constructs of this classification, however a new measure for Japanese people with
      knee osteoarthritis was developed based on these constructs. SUMMARY: There have
      been significant developments in the conceptual approach to measuring activity
      limitation. Measures are needed that operationalize activity limitation as
      defined by the International Classification of Functioning, Disability and Health
      (within or ideally across cultures), providing a common underlying construct for
      measures and hence facilitating comparability across studies.

PMID- 16896297
TI  - Animal models of osteoarthritis: lessons learned while seeking the "Holy Grail".
AB  - PURPOSE OF REVIEW: Difficulties in studying osteoarthritis in humans that stem
      from both the low sensitivity of diagnostic tools and the low availability of
      diseased tissues explain why research on animal models remains highly dynamic.
      This review will summarize the recent advances in this field. RECENT FINDINGS:
      With regard to the etiology of osteoarthritis, synovial macrophages mediate
      osteophyte formation, whereas increased ligament laxity could be responsible for
      spontaneous osteoarthritis in guinea pigs. The concomitant changes in subchondral
      bone and cartilage reported in several models, and the structure-modifying
      effects of some bone inhibitors have confirmed the importance of bone in
      osteoarthritis. With regard to cartilage pathobiology, ADAMTS-5 is the major
      aggrecanase responsible for cartilage destruction, whereas inadequate control of
      oxidative stress and decreased expression of transforming growth factor-beta
      receptors could predispose to osteoarthritis. New models include a postmenopausal
      rat model, the groove model and a joint-specific bone morphogenetic receptor
      deficient mouse. The iodoacetate model was also validated as the first pain model
      of osteoarthritis. SUMMARY: In view of the multiple animal models available,
      there is a need to reach a consensus on one or several gold standard animal
      model(s). New studies indicate that important differences in therapeutic response
      exist between young and old animals, and between spontaneous and surgical models,
      suggesting that not all models are adequate models of osteoarthritis.

PMID- 16896299
TI  - Bibliography. Current world literature. Systemic lupus erythematosus and Sjogren
      syndrome.

PMID- 16896298
TI  - Complement dysfunction in hemolytic uremic syndrome.
AB  - PURPOSE OF REVIEW: Hemolytic uremic syndrome is a rare disease of
      microangiopathic hemolytic anemia, low platelet count and is associated with
      renal impairment. The atypical form, which occurs in adult patients, is
      associated with defective complement control. RECENT FINDINGS: Recent data show
      that atypical hemolytic uremic syndrome is a genetic disease and gene mutations
      have been reported for factor H, membrane cofactor protein/CD46 and factor I. All
      corresponding gene products act in concert and control the activity of the
      complement convertase C3bBb. This enzyme initiates the alternative pathway as
      well as amplification of the complement system. Similar to genetic defects,
      autoantibodies which bind to factor H have been linked to the disease. Defective
      complement control resulting in hemolytic uremic syndrome explains the disease
      mechanism and allows improved diagnosis and therapy. SUMMARY: The atypical form
      of hemolytic uremic syndrome is associated with defective complement control and
      inappropriate protein function and may influence disease progression and provide
      new ways for treatment. Positive effects were reported upon substitution of a
      defective protein by plasma exchange or plasmaphoreses. The disease recurrence
      rate for renal transplants depends on the type of gene mutated; patients with
      mutations in the membrane cofactor protein gene have a better prognosis than
      patients with mutations in other genes.

PMID- 16896300
TI  - Assessment of myocardial viability using delayed enhancement magnetic resonance
      imaging at 3.0 Tesla.
AB  - OBJECTIVE: Cardiac magnetic resonance imaging (MRI) at 3.0 T has recently become
      available and potentially provides a significant improvement of tissue contrast
      in T1-weighted imaging techniques relying on Gd-based contrast enhancement.
      Imaging at high-field strength may be especially advantageous for methods relying
      on strong T1-weighting and imaging after contrast material administration. The
      aim of this study was to compare cardiac delayed enhancement (DE) MRI at 3.0 T
      and 1.5 T with respect to image quality, signal-to-noise ratio (SNR), and
      contrast-to-noise ratio (CNR) between infarcted and normal myocardium. MATERIALS
      AND METHODS: Forty consecutive patients with history of myocardial infarction
      were examined at 3.0 T (n = 20) or at 1.5 T (n = 20). Myocardial function was
      assessed using cine steady-state-free-precession (SSFP) sequences (TR 3.1
      milliseconds, TE 1.6 milliseconds, flip angle 70 degrees , and a matrix of 168 x
      256 at 1.5 T and TR 3.4 milliseconds, TE 1.7 milliseconds, flip angle 50 degrees
      and a matrix of 168 x 256 at 3.0 T), acquired in long- and short-axes views. DE
      images were obtained 15 minutes after the administration of 0.15 mmol of Gd
      DTPA/kg body weight using a segmented inversion recovery prepared gradient echo
      sequence at 1.5 T (TR 9.6 milliseconds, TE 4.4 milliseconds, flip angle 25
      degrees , matrix 160 x 256, bandwidth 140 Hertz/pixel) and at 3.0 T (TR 9.8
      milliseconds, TE 4.3 milliseconds, flip angle 30 degrees , matrix 150 x 256,
      bandwidth 140 Hertz/pixel). For image analysis, standardized SNR and CNR
      measurements were performed in infarcted and remote myocardial regions. Two
      independent observers rated image quality on a 4-point scale (0 = poor image
      quality, 1 = sufficient image quality, 2 = good image quality, 3 = excellent
      image quality). RESULTS: High diagnostic image quality was obtained in all
      patients. Rating of mean image quality was 2.2 +/- 0.8 at 1.5 T and 2.5 +/- 0.6
      at 3.0 T (P = 0.012) for observer 1 and 2.2 +/- 0.7 at 1.5 T and 2.6 +/- 0.6 at
      3.0 T (P = 0.003) for observer 2, respectively. Interobserver agreement was good
      (kappa = 0.68 at 1.5 T and 0.78 at 3.0 T). SNR measurements yielded a mean SNR of
      37.8 +/- 13.9/22.9 +/- 6.0 in infarcted myocardium (P < 0.001) and 5.6 +/-
      2.2/5.9 +/- 2.4 in normal myocardium (P = 0.45) at 3.0 T/1.5 T, respectively. CNR
      measurements revealed mean values of 32.4 +/- 13.0/16.7 +/- 5.4 (P< 0.001) at 3.0
      T/1.5 T, respectively. CONCLUSIONS: Delayed enhancement MRI at 3.0 T is feasible
      and provides superior image quality compared with 1.5 T. Furthermore, using
      identical contrast doses, increased SNR and CNR values were recorded at 3.0 T.

PMID- 16896301
TI  - Coronary artery calcium scoring with multislice computed tomography: in vitro
      assessment of a low tube voltage protocol.
AB  - OBJECTIVES: We sought to compare an 80-kVp coronary calcium scoring protocol with
      the standard protocol of 120 kVp in terms of accuracy and reproducibility and to
      assess its dose reduction potential. MATERIALS AND METHOD: An anthropomorphic
      heart phantom with calcium cylinders was scanned with different tube currents at
      80 kVp and 120 kVp using a 16-slice multislice CT (MSCT) scanner. An adapted
      threshold for 80 kVp was calculated. Accuracy and reproducibility for calcium
      mass, volume, and Agatston score were analyzed using F-tests. The radiation doses
      needed to produce artifact-free images were determined. RESULTS: Accuracy
      (measurement errors: mass 120 kVp +4.6%, mass 80 kVp -6.9%, volume 120 kVp
      +78.8%, volume 80 kVp +58.2%) and reproducibility (F-tests: mass: P = 0.4998,
      volume: P = 0.9168, Agatston: P = 0.5422) were comparable at both tube voltages.
      Avoiding the appearance of artificial lesions, a CTDI(w,eff) of 10.7 mGy was
      needed at 120 kVp versus 4.6 mGy at 80 kVp (dose reduction of 57%). CONCLUSIONS:
      Using an 80-kVp protocol in coronary calcium scoring, a relevant dose reduction
      is possible without compromising reproducibility and accuracy.

PMID- 16896302
TI  - Computed tomography calcium quantification as a measure of atherosclerotic plaque
      morphology and stability.
AB  - OBJECTIVES: We examined the relationship between computed tomography (CT)
      quantified calcium and histopathologic atherosclerotic plaque morphology and
      rupture. MATERIALS AND METHODS: Seven aortae were harvested from autopsy cases.
      All were scanned, ex vivo, on a 16-slice CT scanner and CT calcium scores (CTCS)
      were calculated using a Siemens Calcium Scoring package. The aorta segments were
      physically cross sectioned at 3-mm intervals corresponding to CT reconstructions.
      Two pathologists evaluated the cross sections for histology calcium score (HCS),
      plaque fibrous cap disruption, overlying thrombus, internal hemorrhage, size,
      lipid content, and inflammation. CT and histology data were subsequently paired
      using predetermined quadrant and slice conventions. RESULTS: Three hundred forty
      nine aorta cross sections yielded 41 atherosclerotic plaques. Eleven plaques
      demonstrated plaque disruption and thrombosis and all contained calcium. CTCS was
      not significantly different between atherosclerotic plaques with and without
      evidence of disruption/thrombosis (F[1,30] = 1.525, P = 0.227). CT was 100%
      sensitive for nodular calcification, but only 56% (5 of 9 plaques) sensitive for
      non-nodular calcification. There was no significant relationship between CTCS and
      intraplaque hemorrhage, lipid content, inflammation, and plaque size (P = 0.179,
      P = 0.230, P = 0.314, and P = 0.054). There was significant correlation between
      CTCS and HCS (Pearson coefficient = 0.535; P < 0.01). CONCLUSIONS: Calcium
      quantity does not appear to predict plaque morphology or likelihood of rupture.
      CT has lower sensitivity for non-nodular compared with nodular calcification.

PMID- 16896303
TI  - Comparison of different radiography systems in an experimental study for
      detection of forearm fractures and evaluation of the Muller-AO and Frykman
      classification for distal radius fractures.
AB  - OBJECTIVES: We sought to compare the diagnostic performance of screen-film
      radiography, storage-phosphor radiography, and a flat-panel detector system in
      detecting forearm fractures and to classify distal radius fractures according to
      the Muller-AO and Frykman classifications compared with the true extent, depicted
      by anatomic preparation. MATERIALS AND METHODS: A total of 71 cadaver arms were
      fractured in a material testing machine creating different fractures of the
      radius and ulna as well as of the carpal bones. Radiographs of the complete
      forearm were evaluated by 3 radiologists, and anatomic preparation was used as
      standard of reference in a receiver operating curve analysis. RESULTS: The
      highest diagnostic performance was obtained for the detection of distal radius
      fractures with area under the receiver operating curve (AUC) values of 0.959 for
      screen-film radiography, 0.966 for storage-phosphor radiography, and 0.971 for
      the flat-panel detector system (P > 0.05). Exact classification was slightly
      better for the Frykman (kappa values of 0.457-0.478) compared with the Muller-AO
      classification (kappa values of 0.404-0.447), but agreement can be considered as
      moderate for both classifications. CONCLUSIONS: The 3 imaging systems showed a
      comparable diagnostic performance in detecting forearm fractures. A high
      diagnostic performance was demonstrated for distal radius fractures and
      conventional radiography can be routinely performed for fracture detection.
      However, compared with anatomic preparation, depiction of the true extent of
      distal radius fractures was limited and the severity of distal radius fractures
      tends to be underestimated.

PMID- 16896304
TI  - Dynamic contrast-enhanced magnetic resonance imaging in the assessment of early
      response to tumor necrosis factor alpha in a colon carcinoma model.
AB  - OBJECTIVE: We describe the effects of tumor necrosis factor alpha (TNFalpha) on
      tumor microvasculature in a murine colon carcinoma model using serial dynamic
      contrast-enhanced (DCE) magnetic resonance imaging (MRI). MATERIAL AND METHODS:
      Mice with subcutaneous murine colon carcinomas (MC-38) were imaged at 4.7 T after
      administration of 0.2 mmol/kg gadolinium-DTPA. Both treated and control mice
      (each group, n = 4), were scanned at baseline and 2, 4, 6, and 96 hours. A 2
      compartment pharmacokinetic model generated parameters such as K, kep, and
      initial area under the gadolinium concentration curve (IAUC). RESULTS: The
      treatment group revealed significant differences in K at all time points after
      TNFalpha. kep and IAUC were significantly reduced at 2, 6, and 96 hours. The
      coefficient of variation in control animals ranged from 0.13 for IAUC to 0.30 for
      K. Mild histologic changes were observed at 2 to 6 hours, but considerable
      central necrosis with a vascular tumor rim was seen at 96 hours. CONCLUSION: DCE
      MRI can be used to detect early effects of TNFalpha. Serial DCE MRI is a
      promising tool in assessing the early effects of antivascular therapies.

PMID- 16896305
TI  - Renal magnetic resonance angiography at 3.0 Tesla using a 32-element phased-array
      coil system and parallel imaging in 2 directions.
AB  - PURPOSE: The aim of the present study was to assess the feasibility of renal
      magnetic resonance angiography at 3.0 T using a phased-array coil system with 32
      coil elements. Specifically, high parallel imaging factors were used for an
      increased spatial resolution and anatomic coverage of the whole abdomen.
      MATERIALS AND METHODS: Signal-to-noise values and the g-factor distribution of
      the 32 element coil were examined in phantom studies for the magnetic resonance
      angiography (MRA) sequence. Eleven volunteers (6 men, median age of 30.0 years)
      were examined on a 3.0-T MR scanner (Magnetom Trio, Siemens Medical Solutions,
      Malvern, PA) using a 32-element phased-array coil (prototype from In vivo Corp.).
      Contrast-enhanced 3D-MRA (TR 2.95 milliseconds, TE 1.12 milliseconds, flip angle
      25-30 degrees , bandwidth 650 Hz/pixel) was acquired with integrated generalized
      autocalibrating partially parallel acquisition (GRAPPA), in both phase- and slice
      encoding direction. Images were assessed by 2 independent observers with regard
      to image quality, noise and presence of artifacts. RESULTS: Signal-to-noise
      levels of 22.2 +/- 22.0 and 57.9 +/- 49.0 were measured with (GRAPPAx6) and
      without parallel-imaging, respectively. The mean g-factor of the 32-element coil
      for GRAPPA with an acceleration of 3 and 2 in the phase-encoding and slice
      encoding direction, respectively, was 1.61. High image quality was found in 9 of
      11 volunteers (2.6 +/- 0.8) with good overall interobserver agreement (k = 0.87).
      Relatively low image quality with higher noise levels were encountered in 2
      volunteers. CONCLUSION: MRA at 3.0 T using a 32-element phased-array coil is
      feasible in healthy volunteers. High diagnostic image quality and extended
      anatomic coverage could be achieved with application of high parallel imaging
      factors.

PMID- 16896307
TI  - Synaptic vulnerability in neurodegenerative disease.
AB  - Recent developments in our understanding of the pathophysiological mechanisms
      underlying degeneration in both the central and peripheral nervous systems have
      highlighted the critical role that synapses play in the instigation and
      progression of neuronal loss. In fact, several lines of evidence suggest that
      previous attempts to delay the onset and progression of clinical symptoms in a
      broad range of neurodegenerative diseases may have been unsuccessful as a result
      of a failure to protect synaptic compartments. As a result, the synapse needs to
      be viewed as an important target for the development of novel protective
      treatments aimed at preventing or slowing disease progression. We summarize
      important findings from human studies and animal models demonstrating common
      synaptic vulnerability across several neurodegenerative diseases. We also discuss
      recent developments in our understanding of degenerative mechanisms that are
      known to be localized to synapses and suggest potential ways to harness this
      understanding to develop synaptoprotective strategies for neurodegenerative
      disease.

PMID- 16896306
TI  - Analysis of change patterns of microcomputed tomography 3-dimensional bone
      parameters as a high-throughput tool to evaluate antiosteoporotic effects of
      agents at an early stage of ovariectomy-induced osteoporosis in mice.
AB  - OBJECTIVES: The purposes of this study were to develop an osteoporosis model in a
      short period of 2 weeks after ovariectomy in mice and to investigate whether
      analysis of microcomputed tomography (muCT) 3-dimensional bone parameters could
      provide useful information on the mechanism of action of antiosteoporotic agents.
      MATERIALS AND METHODS: Mice were ovariectomized (OVX) or sham-operated, and the
      OVX mice were treated daily with 17beta-estradiol (E2), parathyroid hormone
      (PTH[1-34]), raloxifene, rolipram, or vehicle for 2 weeks. On day 14 post-OVX,
      the left femur bones were removed and then the distal metaphyseal bone was
      analyzed by both muCT and histomorphometry. RESULTS: The trabecular bone volume,
      thickness, number, and connectivity significantly decreased and the number of
      osteoclasts increased in OVX mice. Treatment of OVX animals with each of the 4
      antiosteoporotic agents significantly increased the bone volume and improved the
      bone architecture. However, the improvement of trabecular thickness in the
      rolipram-treated group and that of cortical thickness in the PTH(1-34)-treated
      group were the most marked, whereas the improvement of connectivity in the
      rolipram-treated group was the least among the drug-treated groups. These
      different improving effects of agents on the bone parameters reflect the
      differential effects of these agents on bone formation and bone resorption.
      CONCLUSIONS: This study demonstrated the feasibility of evaluating the effect of
      the antiosteoporotic agents within 2 weeks after ovariectomy in mice. The muCT
      analysis may serve as a valuable tool, specifically in a high-throughput
      pharmacological screening test, offering useful information regarding the effects
      of test compounds on both bone resorption and formation.

PMID- 16896309
TI  - POLG1 mutations associated with progressive encephalopathy in childhood.
AB  - We have identified compound heterozygous missense mutations in POLG1, encoding
      the mitochondrial DNA polymerase gamma (Pol gamma), in 7 children with
      progressive encephalopathy from 5 unrelated families. The clinical features in 6
      of the children included psychomotor regression, refractory seizures, stroke-like
      episodes, hepatopathy, and ataxia compatible with Alpers-Huttenlocher syndrome.
      Three families harbored a previously reported A467T substitution, which was found
      in compound with the earlier described G848S or the W748S substitution or a novel
      R574W substitution. Two families harbored the W748S change in compound with
      either of 2 novel mutations predicted to give an R232H or M1163R substitution.
      Muscle morphology showed mitochondrial myopathy with cytochrome c oxidase (COX)
      deficient fibers in 4 patients. mtDNA analyses in muscle tissue revealed mtDNA
      depletion in 3 of the children and mtDNA deletions in the 2 sibling pairs.
      Neuropathologic investigation in 3 children revealed widespread cortical
      degeneration with gliosis and subcortical neuronal loss, especially in the
      thalamus, whereas there were only subcortical neurodegenerative findings in
      another child. The results support the concept that deletions as well as
      depletion of mtDNA are involved in the pathogenesis of Alpers-Huttenlocher
      syndrome and add 3 new POLG1 mutations associated with an early-onset
      neurodegenerative disease.

PMID- 16896308
TI  - Interlaboratory comparison of assessments of Alzheimer disease-related lesions: a
      study of the BrainNet Europe Consortium.
AB  - This interlaboratory study evaluated the reproducibility of the assessments of
      neuritic plaques and neurofibrillary tangles (NFTs)--the hallmark lesions of
      Alzheimer disease--and compared the staining between the BrainNet Europe centers.
      To reduce the topography-related inconsistencies in assessments, we used a 2-mm
      tissue microarray (TMA) technique. The TMA block included 42 core samples taken
      from 21 paraffin blocks. The assessments were done on Bielschowsky and Gallyas
      silver stains using an immunohistochemical (IHC) method with antibodies directed
      to beta-amyloid (IHC/Abeta) and hyperphosphorylated tau (IHC/HPtau). The staining
      quality and the assessments differed between the participants, being most diverse
      with Bielschowsky (good/acceptable stain in 53% of centers) followed by Gallyas
      (good/acceptable stain in 57%) and IHC/Abeta (good/acceptable stain in 71%). The
      most uniform staining quality and assessment was obtained with the IHC/HPtau
      method (good/acceptable stain in 94% of centers). The neuropathologic diagnostic
      protocol (Consortium to Establish a Registry for Alzheimer Disease, Braak and
      Braak, and the National Institute of Aging and Reagan [NIA-Reagan] Institute)
      that was used significantly influenced the agreement, being highest with NIA
      Reagan (54%) recommendations. This agreement was improved by visualization of
      NFTs using the IHC/HPtau method. Therefore, the IHC/HPtau methodology to
      visualize NFTs and neuropil threads should be considered as a method of choice in
      a future diagnostic protocol for Alzheimer disease.

PMID- 16896310
TI  - Paired overexpression of ErbB3 and Sox10 in pilocytic astrocytoma.
AB  - Pilocytic astrocytoma (PA) is the most common glioma of childhood. Despite their
      relatively high incidence, the molecular mechanisms responsible for tumorigenesis
      and growth of PA are poorly understood. Previous in vitro studies in our
      laboratory showed that despite the absence of ErbB1, PA was sensitive to ErbB1
      tyrosine kinase inhibitor gefitinib. To identify alternative targets of gefitinib
      in PA, we studied other members of the ErbB receptor tyrosine kinase family that
      have been identified in brain tumors. Using gene expression microarray and
      Western blot analyses, we found that ErbB3 is highly overexpressed in PA compared
      with other pediatric brain tumors (glioblastoma, ependymoma, medulloblastoma,
      atypical teratoid/rhabdoid tumor, and choroid plexus papilloma). Developmental
      biology studies have identified Sox10 as a regulator of ErbB3 expression during
      development of the neural crest. Investigation of Sox10 in PA revealed that it is
      highly overexpressed relative to other pediatric brain tumors, lending support to
      the theory that Sox10-regulated overexpression of ErbB3 may be driving growth in
      PA. Sox10-regulated ErbB3 overexpression is a novel insight into the biology of
      PA, suggests possible recapitulation of developmental pathways in tumorigenesis,
      and presents possible targets for therapeutic intervention that might be used for
      hypothalamic variants not amenable to surgical cure.

PMID- 16896311
TI  - Chromosomal translocations fusing the BCL6 gene to different partner loci are
      recurrent in primary central nervous system lymphoma and may be associated with
      aberrant somatic hypermutation or defective class switch recombination.
AB  - Primary central nervous system lymphomas (PCNSLs) are diffuse large B cell
      lymphomas confined to the brain. Only minimal data exist on chromosomal
      aberrations underlying PCNSLs. We studied 41 PCNSLs by fluorescence in situ
      hybridization for breakpoints affecting the BCL6 locus in chromosomal band 3q27.
      Of 37 cases evaluable, 14 (38%) carried a breakpoint in the BCL6 locus. Two of
      these showed juxtaposition of BCL6 to the IGH locus. In 4 cases, the BCL6
      breakpoints were cloned using long-distance inverse polymerase chain reaction.
      All breakpoints were located within the BCL6 major translocation cluster. The
      translocation partners were the IGH gene in 14q32.33, the IGL gene in 22q11.22,
      and the histone 1 H4I gene in 6p22.1. In the fourth case, a deletion in 3q leads
      to loss of an 837-kb fragment extending from the first intron of BCL6 to the
      third intron of the lipoma-preferred partner (LPP) gene. This deletion may bring
      the BCL6 gene under the control of regulatory elements of the LPP gene or the
      miRNA-28 gene located in intron 4 of LPP. DNA sequence analysis of the junctional
      sequences provided evidence that aberrant class switch recombination or somatic
      hypermutation may be involved in the generation of BCL6 translocations.

PMID- 16896313
TI  - Exploring the distinctive biological characteristics of pilocytic and low-grade
      diffuse astrocytomas using microarray gene expression profiles.
AB  - Although World Health Organization (WHO) grade I pilocytic astrocytomas and grade
      II diffuse astrocytomas have been classified for decades as different
      clinicopathologic entities, few, if any, data are available on the biologic
      features explaining these differences. Although more than 50 microarray-related
      studies have been carried out to characterize the molecular profiles of
      astrocytic tumors, we have identified only 11 that provide sound data on low
      grade astrocytomas. We have incorporated these data into a comparative analysis
      for the purpose of identifying the most relevant molecular markers characterizing
      grade I pilocytic and grade II diffuse astrocytomas. Our analysis has identified
      various interesting genes that are differentially expressed in either grade I or
      grade II astrocytomas when compared with normal tissue and/or high-grade (WHO
      grade III and IV) astrocytomas. A large majority of these genes encode adhesion,
      extracellular matrix, and invasion-related proteins. Interestingly, a group of 6
      genes (TIMP4, C1NH, CHAD, THBS4, IGFBP2, and TLE2) constitute an expression
      profile characteristic of grade I astrocytomas as compared with all other
      categories of tissue (normal brain, grade II, and high-grade astrocytomas). The
      end products (proteins) of these genes act as antimigratory compounds, a fact
      that could explain why pilocytic astrocytomas behave as compact (well
      circumscribed) tumors as opposed to all the other astrocytic tumor types that
      diffusely invade the brain parenchyma. Having validated these molecular markers
      by means of real-time reverse transcriptase-polymerase chain reaction, an
      integrated model was proposed illustrating how and why pilocytic astrocytomas
      constitute a distinct biologic and pathologic entity when compared with diffuse
      astrocytomas.

PMID- 16896312
TI  - MMP-12, MMP-3, and TIMP-1 are markedly upregulated in chronic demyelinating
      theiler murine encephalomyelitis.
AB  - Theiler murine encephalomyelitis (TME) represents a highly relevant viral model
      for multiple sclerosis. Matrix metalloproteinases (MMPs) degrade extracellular
      matrix molecules and are involved in demyelination processes. To elucidate their
      impact on demyelination in TME, spinal cords of TME virus (TMEV)-infected SJL/J
      mice were taken at 9 different time points postinfection (pi) ranging from 1 hour
      to 196 days pi and investigated for the expression of TMEV, MMP-2, -3, -7, -9, 
      10, -11, -12, -13, -14, -15, -24, and TIMP-1 to -4 by reverse transcription
      quantitative polymerase chain reaction (RT-qPCR). High TMEV RNA levels were
      detectable throughout the observation period using RT-qPCR. In addition, TMEV RNA
      was visualized within demyelinated lesions by in situ hybridization. MMP-3 mRNA
      was significantly upregulated at 1 day pi and again in the late phase of
      infection. TIMP-1 mRNA was significantly elevated throughout the observation
      period. MMP-12 mRNA was most prominently upregulated in the late phase of
      infection and MMP-12 protein was localized in intralesional microglia/macrophages
      and astrocytes by immunohistochemistry. In summary, in early TMEV infection, MMP
      3 and TIMP-1 mRNA upregulation might be directly virus-induced, whereas
      persistent TMEV infection directly or indirectly stimulated MMP-12 production in
      microglia/macrophages and astrocytes and might account for ongoing demyelination
      in TME.

PMID- 16896314
TI  - Relationship among alpha-synuclein accumulation, dopamine synthesis, and
      neurodegeneration in Parkinson disease substantia nigra.
AB  - The histologic hallmark of Parkinson disease (PD) is loss of pigmented neurons in
      the substantia nigra (SN) and locus ceruleus (LC) with accumulation of alpha
      synuclein (alphaS). It has been reported that tyrosine hydroxylase (TH)-negative
      pigmented neurons are present in these nuclei of patients with PD. However, the
      relationship between TH immunoreactivity and alphaS accumulation remains
      uncertain. We immunohistochemically examined the SN and LC from patients with PD
      (n = 10) and control subjects (n = 7). A correlation study indicated a close
      relationship among decreased TH immunoreactivity, alphaS accumulation, and
      neuronal loss. In addition, 10% of pigmented neurons in the SN and 54.9% of those
      in the LC contained abnormal alphaS aggregates. Moreover, 82.3% of pigmented
      neurons bearing alphaS aggregates in the SN and 39.2% of those in the LC lacked
      TH immunoreactivity, suggesting that pigmented neurons in the SN have a greater
      tendency to lack TH activity than those in the LC. Recent studies have shown that
      this decrease of TH activity leads to a decrease of cytotoxic substances and that
      decreased dopamine synthesis leads to a reduction of cytotoxic alphaS oligomers.
      Therefore, the decrease of TH immunoreactivity in pigmented neurons demonstrated
      here can be considered to represent a cytoprotective mechanism in PD.

PMID- 16896315
TI  - Intrathecal upregulation of granulocyte colony stimulating factor and its
      neuroprotective actions on motor neurons in amyotrophic lateral sclerosis.
AB  - To investigate cytokine/chemokine changes in amyotrophic lateral sclerosis (ALS),
      we simultaneously measured 16 cytokine/chemokines (interleukin [IL]-1beta, IL-2,
      IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12 [p70], IL-13, IL-17, interferon-gamma,
      tumor necrosis factor-alpha, granulocyte colony stimulating factor [G-CSF],
      macrophage chemoattractant protein-1 [MCP-1], and macrophage inflammatory protein
      1beta) in cerebrospinal fluid (CSF) and sera from 37 patients with sporadic ALS
      and 33 controls using a multiplexed fluorescent bead-based immunoassay. We also
      conducted immunohistochemical analyses from 8 autopsied ALS cases and 6
      nonneurologic disease controls as well as cell culture analyses of relevant
      cytokines and their receptors. We found that concentrations of G-CSF and MCP-1
      were significantly increased in ALS CSF compared with controls. In spinal cords,
      G-CSF was expressed in reactive astrocytes in ALS cases but not controls, whereas
      G-CSF receptor expression was significantly decreased in motor neurons of spinal
      cords from ALS cases. Biologically, G-CSF had a protective effect on the NSC34
      cell line under conditions of both oxidative and nutritional stress. We suggested
      that G-CSF has potentially neuroprotective effects on motor neurons in ALS and
      that downregulation of its receptor might contribute to ALS pathogenesis. On the
      other hand, MCP-1 correlated with disease severity, which may aggravate motor
      neuron damage.

PMID- 16896316
TI  - Proteomic analysis of inclusion body myositis.
AB  - Sporadic inclusion body myositis (IBM) is the most frequently acquired
      inflammatory myopathy of late adult life, yet its diagnostic criteria and
      pathogenesis remain poorly defined. Because effective treatment is lacking,
      research efforts have intensified to identify specific markers for this
      debilitating disorder. In this study, proteomic analysis of 4 cases of sporadic
      IBM was compared with 5 cases of inflammatory myopathy without clinicopathologic
      features of IBM to distinguish the IBM-specific proteome. Proteins were separated
      by 2-dimensional polyacrylamide gel electrophoresis and profiled by mass
      spectrometric sequencing. Expression of most proteins remained unchanged;
      however, 16 proteins were upregulated and 6 proteins were downregulated in IBM
      compared with cases of non-IBM inflammatory myopathy. These IBM-specific proteins
      included apolipoprotein A-I, amyloid beta precursor protein, and transthyretin,
      which have been associated with amyloidosis; superoxide dismutase, enolase, and
      various molecular chaperones indicate perturbations in detoxification, energy
      metabolism, and protein folding, respectively. The IBM-downregulated proteins
      mainly serve as carriers for muscle contraction and other normal muscle
      functions. We further applied Western blot and immunohistochemistry to verify the
      proteomic findings. This study validates proteomics as a powerful tool in the
      study of muscle disease and indicates a unique pattern of protein expression in
      IBM.

PMID- 16896337
TI  - A case of intraroot cauda equina cavernous angioma: clinical considerations.
AB  - STUDY DESIGN: Case report and literature review. OBJECTIVE: Intradural
      extramedullary cavernoma is a rare condition with only 23 cases reported in the
      literature. Most cases described adhere to spinal root or spinal cord. We report
      an example of this rare entity located within the sheets of one cauda equina
      nerve root. SETTING: Rome, Italy. METHODS: The authors report clinical,
      radiological, surgical, and pathological features of intraroot cavernoma with a
      literature review. RESULTS: Patient was operated. One year after surgery, he was
      healthy. CONCLUSION: Lumbar intradural cavernous angioma may present with
      sciatalgia, low-back pain, neurological deficit, or, more rarely with
      subarachnoid hemorrhage or hydrocephalus. They are treated successfully with
      surgical resection but preoperative status is a predicting factor for outcome.
      Sometimes the sacrifice of the spinal root is inevitable because, as in present
      case, the cavernous angioma is included in the nerve root. These lesions are rare
      and benign lesions. It is important for neurosurgeons to be aware of the
      existence of this entity to avoid preoperative misdiagnosis with tumor.

PMID- 16896338
TI  - A case of unusual substance abuse causing myeloneuropathy.
AB  - STUDY DESIGN: Case report. OBJECTIVES: Examine an unusual drug related case of
      myeloneuropathy as well as the pathophysiology of nitrous oxide induced subacute
      combined degeneration. SETTING: Major metropolitan teaching hospital - Princess
      Alexandra Hospital, Queensland, Australia. METHODS: Review case notes,
      investigations, relevant medical literature and epidemiological data. RESULTS: A
      23-year-old female developed a myeloneuropathy and encephalopathy after an 8
      month history of nitrous oxide abuse. Her presentation was complicated by acute
      renal failure, deep vein thrombosis (DVT) and pulmonary embolism (PE) as well as
      severe cognitive deficits. After eight months of multidisciplinary rehabilitation
      the patient is able to walk short distances with mobility aids and is able to
      manage self cares. However, she still requires a wheelchair for long distances
      and will have significant residual neurological deficits. CONCLUSION: The abuse
      of nitrous oxide has potentially serious outcomes that require discussion of
      issues related to harm minimisation and health promotion.

PMID- 16896340
TI  - Nanoscale resolution in GFP-based microscopy.
AB  - We report attainment of subdiffraction resolution using stimulated emission
      depletion (STED) microscopy with GFP-labeled samples. The approximately 70 nm
      lateral resolution attained in this study is demonstrated by imaging GFP-labeled
      viruses and the endoplasmic reticulum (ER) of a mammalian cell. Our results mark
      the advent of nanoscale biological microscopy with genetically encoded markers.

PMID- 16896339
TI  - Sub-diffraction-limit imaging by stochastic optical reconstruction microscopy
      (STORM).
AB  - We have developed a high-resolution fluorescence microscopy method based on high
      accuracy localization of photoswitchable fluorophores. In each imaging cycle,
      only a fraction of the fluorophores were turned on, allowing their positions to
      be determined with nanometer accuracy. The fluorophore positions obtained from a
      series of imaging cycles were used to reconstruct the overall image. We
      demonstrated an imaging resolution of 20 nm. This technique can, in principle,
      reach molecular-scale resolution.

PMID- 16896341
TI  - Genome-wide characterisation of hepatitis B mutations involved in clinical
      outcome.
AB  - Infection with the hepatitis B virus (HBV) leads to different disease outcomes,
      which can be broadly divided into three categories: acute mild infection,
      'fulminant' and chronic hepatitis (long-term persistent form of the infection).
      The factors that influence the development of these different disease states are
      poorly understood and may include viral polymorphisms. To investigate this
      possibility, we analysed 116 published complete HBV genomes for which we knew
      disease outcome and had access to associated information on patients (age, sex
      and geographic origin). Our best statistical model correctly classified 72% of
      the cases and retained age and sex of the patient, as well as 29 candidate
      mutations. With the exception of one mutation in the X gene, all were located in
      the viral polymerase, suggesting this gene plays a critical role in clinical
      outcome. Our results highlight the importance of the genetics of HBV strains in
      the evolution of the disease and demonstrate that disease outcome can be
      predicted to a surprisingly large extent with a limited number of host and viral
      factors.

PMID- 16896342
TI  - Spatial patterns of genetic diversity across European subspecies of the mountain
      hare, Lepus timidus L.
AB  - Fossil evidence shows that populations of species that currently inhabit arctic
      and boreal regions were not isolated in refugia during glacial periods, but
      instead maintained populations across large areas of central Europe. These
      species commonly display little reduction in genetic diversity in northern areas
      of their range, in contrast to many temperate species. The mountain hare
      currently inhabits both temperate and arctic-boreal regions. We used nuclear
      microsatellite and mtDNA sequence data to examine population structure and
      alternate phylogeographic hypotheses for the mountain hare, that is, temperate
      type (lower genetic diversity in northern areas) and arctic-boreal type (high
      northern genetic diversity). Both data sets revealed concordant patterns. Highest
      allelic richness, expected heterozygosity and mtDNA haplotype diversity were
      identified in the most northerly subspecies, indicating that this species more
      closely maps to phylogeographic patterns observed in arctic-boreal rather than
      temperate species. With regard to population structure, the Alpine and
      Fennoscandian subspecies were most genetically similar (F(ST) approximately 0.1).
      These subspecies also clustered together on the mtDNA tree and were assigned with
      highest likelihood to a common Bayesian cluster. This is consistent with fossil
      evidence for intermediate populations in the central European plain, persisting
      well into the postglacial period. In contrast, the geographically close Scottish
      and Irish populations occupied separate Bayesian clusters, distinct clades on the
      mtDNA maximum likelihood tree and were genetically divergent from each other
      (F(ST) > 0.4) indicating the influence of genetic drift, long isolation (possibly
      dating from the late glacial era) and/or separate postglacial colonisation
      routes.

PMID- 16896343
TI  - The genetic analysis of family structured inbreeding depression studies.
AB  - An important question emerging from theoretical studies of mating system
      evolution is whether the fitness of a randomly extracted, fully inbred genotype
      will exceed the mean of outbred individuals. We introduce two statistics (I(1)
      and I(2)) related to the probability of extracting a high line. I(1) and I(2) can
      be estimated from the family structured experimental designs typically used to
      estimate inbreeding depression (ID). Maximum likelihood procedures are developed
      from an explicit genetic model. These yield parameter estimates and provide the
      likelihoods necessary to test hypotheses, for example, whether population-level
      ID is nonzero. Finally, we describe a new publicly available computer program
      titled 'IDG' (Inbreeding Depression Genetics) to execute these procedures.

PMID- 16896344
TI  - A novel CSX/NKX2-5 mutation causes autosomal-dominant AV block: are atrial
      fibrillation and syncopes part of the phenotype?
AB  - The prevalence of congenital heart defects is approximately 1% of all live
      births. Identifying the genes responsible for cardiac malformation is the first
      step to understand pathogenesis. Heterozygous mutations in the CSX/NKX2-5 (NKX2E)
      gene have been identified to cause atrial septal defect (ASD) and/or
      atrioventricular (AV) conduction disturbance in some families. However, there is
      great variability in expressivity of the phenotype between the patients with a
      CSX/NKX2-5 mutation. We screened four sporadic patients and three index cases of
      families with ASD and/or conduction defects. In one of them, a CSX/NKX2-5
      mutation was identified. This novel mutation (p.Tyr256X) was inherited in a three
      generation family causing five individuals to have cardiac anomalies ranging from
      ASD to arrhythmias. Interestingly, all the observed AV conduction disturbances
      were at the nodal level, manifesting first as an AV block of the first degree and
      evolving toward a second-degree block. Atrial fibrillation, previously reported
      in three individuals with CSX/NKX2-5 mutations, was observed in three patients.

PMID- 16896345
TI  - Ulnar-mammary syndrome with dysmorphic facies and mental retardation caused by a
      novel 1.28 Mb deletion encompassing the TBX3 gene.
AB  - Ulnar-mammary syndrome (UMS) is a rare autosomal-dominant disorder caused by
      mutations in TBX3. The condition is characterized by hypoplasia or aplasia of
      upper limbs on the ulnar side, mammary glands and nipples, and of apocrine glands
      in both sexes (MIM #181450). We report on a girl presenting with an UMS like
      phenotype, a dysmorphic facies, and mental retardation. Mutation analysis of TBX3
      and G-banded chromosome analysis from lymphocytes were performed. We used
      microarray-based comparative genomic hybridization (array CGH) to investigate the
      patient's genomic DNA for submicroscopic aberrations. No mutation of the TBX3
      gene was detected in our patient and chromosome analysis revealed a normal female
      karyotype (46,XX). Hybridization of a whole-genome tiling path array consisting
      of more than 36 000 BAC clones revealed an interstitial 1.28 Mb deletion within
      chromosomal band 12q24.21. The deleted region encompasses one known gene, TBX3.
      The deletion and haploinsufficiency of TBX3 was confirmed by fluorescence in situ
      hybridization using BAC clones representing the deletion on the BAC array. To our
      knowledge, this is the first description of TBX3 haploinsufficiency caused by a
      genomic deletion in a patient with UMS. We suggest that the UMS phenotype in
      conjunction with the characteristic facial changes and mental retardation
      observed in our patient is owing to the deletion of TBX3 and the involvement of
      neighbouring genes.

PMID- 16896346
TI  - Three different ABCA4 mutations in the same large family with several
      consanguineous loops affected with autosomal recessive cone-rod dystrophy.
AB  - A large multiplex family presumably affected with autosomal recessive cone-rod
      dystrophy (CRD) was ascertained from Israel. In this family of Christian Arab
      ancestry with six consanguineous loops, linkage analysis failed to identify
      homozygosity in all six nuclear families at any of the three arCORD loci hitherto
      reported. However, homozygosity was found at the CORD3 locus for two nuclear
      families and the segregation of three distinct haplotypes at this locus in the
      whole pedigree suggested the alteration of the ABCA4 gene. This hypothesis was
      confirmed by the identification of three distinct mutations. Subsequently, with
      regard to the wide spectrum of autosomal recessive retinal dystrophies related to
      ABCA4 mutations, the natural history of the disease was revisited in all
      patients. Although the diagnosis of CRD was confirmed in 8/9 patients, the last
      one, aged of 34, displayed typical signs of Stargardt disease without extension
      to the peripheral retina. The results of this study emphasize the pitfalls of
      homozygosity mapping in highly inbred families when the heterozygote carrier
      frequency is particularly high in the general population.

PMID- 16896347
TI  - Brain changes to hypocapnia using rapidly interleaved phosphorus-proton magnetic
      resonance spectroscopy at 4 T.
AB  - Substantial controversy persists in the literature concerning the physiologic
      consequences hypocapnia, or low partial pressure of carbon dioxide (PaCO(2)).
      Invasive animal studies have demonstrated large pH increases (>0.25 U),
      phosphocreatine (PCr) decreases (>30%), and adenosine triphosphate (ATP)
      decreases (>10%) after hyperventilation (HV) (20 mm Hg PaCO(2)). However, using
      magnetic resonance spectroscopy, HV studies in awake humans have demonstrated
      only small pH changes ( approximately 0.05 U) and no changes in PCr or ATP. It
      remains important to ascertain whether this failure to detect PCr changes in
      human studies reflects a true absence of changes, or a limitation in data
      fidelity. The present study used a rapidly interleaved phosphorus-proton
      spectroscopy acquisition from large samples at high magnetic field (4 T), to
      measure pH, PCr, inorganic phosphate, beta-ATP, and lactate changes with high
      temporal and signal sensitivity. Five of six subjects had usable data. During 20
      mins HV, PaCO(2) reached a minimum at 16 mins (17 mm Hg); however, the maximum pH
      change (+0.047) peaked earlier (14 mins). Maximal lactate increases were measured
      at 15 mins. By 10 mins, maximum changes were observed for PCr (-3.4%) and
      inorganic phosphate (+6.4%). No changes in beta-ATP were observed. The peak in
      pH, despite continued decreases in PaCO(2), suggests active buffering during HV.
      These data, and the small magnitude of early PCr and inorganic phosphate changes,
      do not support substantial energy compromise during HV. Other mitigating factors,
      such as anesthesia-induced deregulation of the cerebrovasculature, might have
      contributed to the exaggerated metabolic changes observed in previous animal
      investigations.

PMID- 16896348
TI  - 5-Hydroxy-L-[beta-11C]tryptophan versus alpha-[11C]methyl-L-tryptophan for
      positron emission tomography imaging of serotonin synthesis capacity in the
      rhesus monkey brain.
AB  - The purpose of this study was to compare two positron emission tomography (PET)
      tracers that were developed to follow serotonin (5HT) synthesis by performing
      sequential PET scanning of the same rhesus monkey (n=4) on the same day. alpha
      [11C]Methyl-L-tryptophan ([11C]AMT) and 5-Hydroxy-L-[beta-11C]tryptophan
      ([11C]HTP) are substrates in the first and second enzymatic steps, respectively,
      in the biosynthesis of 5HT. Regional net accumulation rate constants were derived
      from kinetic (two-tissue compartment model with irreversible tracer trapping) and
      graphic (Patlak) analyses, using the arterial plasma concentrations as input. The
      kinetic data analysis showed that the rate constant for the transfer of [11C]HTP
      into the brain (K1) was higher than that for [11C]AMT in the striatum and
      thalamus but was similar in other brain regions. The rate constant for tracer
      trapping (k3) was also higher for [11C]HTP than for [11C]AMT in the striatum
      (0.046+/-0.024 versus 0.019+/-0.006 min(-1)) and thalamus (0.039+/-0.013 versus
      0.016+/-0.007 min(-1)). In agreement with previously reported regional HTP
      accumulation rates, the net accumulation rate constant (K(acc)) for [11C]HTP was
      also higher in these regions than in other brain regions; this is in contrast to
      the uniform distribution of [11C]AMT K(acc) values. This suggests that the
      regional net accumulation rates obtained with these two PET tracers will be of
      different magnitude, which might be related to the activity of each targeted
      enzyme.

PMID- 16896349
TI  - Killer proteases and little strokes--how the things that do not kill you make you
      stronger.
AB  - The phenomenon of ischemic preconditioning was initially observed over 20 years
      ago. The basic tenant is that if stimuli are applied at a subtoxic level, cells
      upregulate endogenous protective mechanisms to block injury induced by subsequent
      stress. Since this discovery, many conserved signaling mechanisms that contribute
      to activation of this potent protective program have been identified in the
      brain. A clinical correlate of this basic research finding can be found in
      patients with a history of transient ischemic attack (TIA), who have a decreased
      morbidity after stroke. In spite of multidisciplinary efforts to design safer,
      more effective stroke therapies, we have thus far failed to translate our
      understanding of endogenous protective pathways to treatments for
      neurodegeneration. This review is designed to provide clinicians and basic
      scientists with an overview of stress biology after TIA and preconditioning,
      discuss new therapeutic strategies to target the protein dysfunction that follows
      ischemic injury, and propose enhanced biochemical profiling to identify
      individuals at risk of stroke after TIA. We pay particular attention to the
      unanticipated consequences of overly aggressive intervention after TIA in which
      we have found that traditional cytotoxic agents such as free radicals and
      apoptosis associated proteases is essential for neuroprotection and communication
      in the stressed brain. These data emphasize the importance of understanding the
      complex interplay between chaperones, apoptotic proteases including caspases, and
      the proteolytic degradation machinery in adaptation to neurological injury.

PMID- 16896350
TI  - Nonlinear neurovascular coupling in rat sensory cortex by activation of
      transcallosal fibers.
AB  - Functional neuroimaging and normal brain function rely on the robust coupling
      between neural activity and cerebral blood flow (CBF), that is neurovascular
      coupling. We examined neurovascular coupling in rat sensory cortex in response to
      direct stimulation of transcallosal pathways, which allows examination of brain
      regions inaccessible to peripheral stimulation techniques. Using laser-Doppler
      flowmetry to record CBF and electrophysiologic recordings of local field
      potentials (LFPs), we show an exponential relation between CBF responses and
      summed LFP amplitudes. Hemodynamic responses were dependent on glutamate receptor
      activation. CNQX, an AMPA receptor blocker, strongly attenuated evoked CBF
      responses and LFP amplitudes at all stimulation frequencies. In comparison, N
      methyl D-aspartate (NMDA) receptor blockade by MK801 attenuated CBF responses at
      high (>7 Hz) but not low (<7 Hz) stimulation frequencies, without affecting
      evoked LFP amplitudes. This shows the limitation of using LFP amplitudes as
      indicators of synaptic activity. 7-Nitroindazole, a neuronal nitric oxide
      synthase inhibitor, and indomethacin, a nonspecific cyclooxygenase inhibitor,
      attenuated the hemodynamic responses by 50%+/-1% and 48%+/-1%, respectively,
      without affecting LFP amplitudes. The data suggest that preserved activity of
      both AMPA and NMDA receptors is necessary for the full CBF response evoked by
      stimulation of rodent interhemispheric connections. AMPA receptor activation
      gives rise to a measurable LFP, but NMDA receptor activation does not. The lack
      of a measurable LFP from neural processes that contribute importantly to CBF may
      explain some of the difficulties in transforming extracellular current or voltage
      measurements to a hemodynamic response.

PMID- 16896351
TI  - The anaphase promoting complex/cyclosome: a machine designed to destroy.
AB  - The anaphase promoting complex/cyclosome (APC/C) is a ubiquitin ligase that has
      essential functions in and outside the eukaryotic cell cycle. It is the most
      complex molecular machine that is known to catalyse ubiquitylation reactions, and
      it contains more than a dozen subunits that assemble into a large 1.5-MDa
      complex. Recent discoveries have revealed an unexpected multitude of mechanisms
      that control APC/C activity, and have provided a first insight into how this
      unusual ubiquitin ligase recognizes its substrates.

PMID- 16896352
TI  - Evidence-based interventional pain medicine: is there any evidence.

PMID- 16896353
TI  - Interventional spine research: the evolution of informed consent.
AB  - The future success of the field of interventional pain medicine depends on proof
      of positive outcomes. Evidence based medicine has an increasing relationship to
      insurance reimbursement. This makes new modes of pain management dependent upon
      human subject research. To succeed physicians must fulfill the ethical and
      regulatory requirements of research, specifically informed consent. History makes
      clear the importance of these ethical principles. Reliance on the beneficence and
      ethics of investigators has failed to protect subjects. This has led to ethical
      codes and governmental intervention. The basis of human research regulation is
      the Nuremberg Code and its underlying ethical principles. This code elucidates
      the requirements of Understanding and Voluntariness in informed consent for
      research. An analysis of these principles helps researchers fulfill the spirit of
      the governmental regulations and highlights the importance of protecting
      individual's rights. The current system of federal oversight of human research is
      cumbersome and inadequate. It leaves large groups of subjects unprotected and its
      lumbering pace often impedes investigators progress in spite of their compliance
      with ethical principles. Reform of these systems, is long overdue and physicians
      must play a role if we are to have efficient ethical human subject research in
      the future.

PMID- 16896354
TI  - Effectiveness of caudal epidural injections in discogram positive and negative
      chronic low back pain.
AB  - Epidural steroid injections are the most commonly used procedures to manage
      chronic low back pain in interventional pain management settings. The overall
      effectiveness of epidural steroid injections has been highly variable, and in the
      role has not been evaluated in patients discographically evaluated. One hundred
      consecutive patients, without evidence of disc herniation or radiculitis, who had
      failed to respond to conservative management with physical therapy, chiropractic
      and/or medical therapy, underwent discography utilizing strict criteria of
      concordant pain, and negative adjacent discs, after being judged to be negative
      for facet joint and/or sacroiliac joint pain utilizing comparative local
      anesthetic blocks. Any other type of response was considered negative. This study
      included 62 patients, who underwent caudal epidural steroid injections with
      Sarapin. They included Group I, comprised of 45 of 55 patients negative on
      provocative discography; and Group II, with 17 of 45 patients with positive
      provocative discography. Results showed that there was significant improvement in
      patients receiving caudal epidural injections, with a decrease in pain associated
      with improved physical, functional, and mental status; decreased narcotic intake,
      and increased return to work. The study showed that at 1 month, 100% of the
      patients evaluated showed significant improvement in both groups; this declined
      to 86% at 3 months in Group I, but remained at 100% in Group II, declining to 60%
      and 64% at 6 months in Group I and Group II, respectfully, with administration of
      one to three injections. Analysis with one to three injections, which included
      all (62) patients showed significant relief in 71% and 65% of the patients at 1
      month, in 67% and 65% at 3 months, and in 47% and 41% at 6 months, in Group I and
      Group II, respectively. In conclusion, caudal epidural injections with or without
      steroids is an effective modality of treatment in managing chronic, persistent
      low back pain failing to respond to conservative modalities of treatments, in
      patients negative for facet joint and sacroiliac joint pain, whether positive or
      negative, on evaluation with provocative discography.

PMID- 16896356
TI  - Is digital subtraction flouroscopy a useful tool for the interventional pain
      physician?
AB  - Most interventional pain physicians are experts in the use of fluoroscopy and
      understand its importance in improving the safety, accuracy and efficacy of
      diagnostic and therapeutic procedures. The addition of digital subtraction may
      enhance the utility of radiography and improve the accuracy of our
      interpretations. This article illustrates the use of the technique in several
      patients. The utility of this enhanced technique in clinical versus research
      application remains to be determined.

PMID- 16896355
TI  - Evaluation of influence of gender, occupational injury, and smoking on chronic
      low back pain of facet joint origin: a subgroup analysis.
AB  - The prevalence of persistent low back pain secondary to involvement of
      lumbosacral facet joints has been described in controlled studies as varying from
      15% to 52% based on types of population and settings studied. Previous studies
      have shown variances in elderly populations, and postlumbar laminectomy patients.
      But no variations were observed in obese patients or patients with somatization
      disorder. Based on the individual results, it appears that facet joint pain may
      be less prevalent in patients with occupational injury and more prevalent in
      women and smokers. This analysis was based on a combination of the results of two
      previous studies with a total number of 320 patients to evaluate the influence of
      gender, occupational injury and smoking on prevalence of facet joint pain. Facet
      joints were investigated with diagnostic blocks initially using lidocaine 1%,
      followed by bupivacaine 0.25%, usually 2 to 4 weeks apart in these studies. The
      prevalence of facet joint pain in men was 38% (95% CI, 29% to 47%) compared to
      43% (95% CI, 36% to 50%) in women; 43% (95% CI, 33% to 53%) in non-smokers,
      compared to 41% (95% CI, 30% to 52%) in heavy smokers; and 28% (95% CI, 18% to
      38%) in occupational injury patients compared to 44% (95% CI, 36% to 52%) with a
      history of gradual onset. False-positive rates varied from 28% to 46%. In
      conclusion, based on the results of this evaluation, women and men, smokers and
      nonsmokers suffer with similar prevalence rates of facet joint pain in chronic
      low back pain; whereas occupational injury patients suffer with lesser prevalence
      (28%) compared to patients with gradual onset (44%) of low back pain.

PMID- 16896357
TI  - Comparison of psychological status of chronic pain patients and the general
      population.
AB  - This study was designed to evaluate the psychological status of 50 individuals
      without chronic pain and without psychotherapeutic drug therapy, Group I, the
      control group; and Group II, a chronic pain group with 100 chronic pain patients.
      All the participants were tested utilizing Millon Clinical Multiaxial Inventory
      III (MCMI-III). Results were analyzed and compared for various clinical
      personality patterns, including personality traits and personality disorders;
      severe personality pathology for schizotypal, borderline and paranoid personality
      pathology; and multiple clinical syndromes, including generalized anxiety
      disorder, somatization disorder, major depression, bipolar manic disorder and
      dysthymic disorder, etc. There were no significant differences noted in clinical
      personality patterns or severe personality pathology. In the analysis of clinical
      syndromes, generalized anxiety disorder (40% vs 14%), somatization disorder (26%
      vs 0%), and major depression (22% vs 4%) were seen in a greater proportion of
      patients in the chronic pain group. The prevalence of psychological disorders in
      the control group was 24%, compared to 55% in chronic pain group. In conclusion,
      this evaluation showed that clinical personality patterns are present in both
      groups of patients. Psychological abnormalities such as generalized anxiety
      disorder, somatization disorder, and major depression are commonly seen in
      chronic pain patients.

PMID- 16896359
TI  - Understanding psychological aspects of chronic pain in interventional pain
      management.
AB  - There is no doubt that chronic pain is recognized as a biopsychosocial phenomenon
      in which biological, psychological, and social factors dynamically interact with
      each other. Thus, the role of psychological factors and understanding chronic,
      persistent disabling pain has been well recognized, but poorly understood.
      Approximately 1/2 to 2/3 of all patients diagnosed with chronic pain manifest to
      various levels of psychological distress. Chronic pain and psychological
      disorders are the two most common elements in the United States. Statistics show
      that, approximately 22% of Americans suffer from a diagnosable mental disorder in
      a given year. In addition, 28% of the American population suffers with chronic
      pain. Depression in chronic pain is the most common condition, followed by
      generalized anxiety disorder, somatization disorder, and drug dependence.
      However, psychogenic pain appears to be the least prevalent of all
      psychopathological issues. Chronic pain disability is a complex psychosocial
      economic phenomenon. There is no data in the literature with regards to treatment
      of personality disorders, anxiety disorders, and somatization disorders in
      managing chronic pain. In contrast, treatment of depression and the influence of
      treatment on outcomes have been studied to some extent. In conclusion, patients
      with chronic pain frequently have psychopathology - most often common depressive
      disorders, anxiety disorders, somatization disorders, drug dependence and
      occasionally personality disorders. This review discusses various issues involved
      with psychopathology in chronic pain including epidemiology; relationship of
      psychopathology to pain; influence of depression, generalized anxiety disorder,
      somatization, and personality disorders on chronic pain, along with diagnosis and
      management in interventional pain management.

PMID- 16896358
TI  - Clinical evaluation of ankylosing spondylitis in Switzerland.
AB  - The purpose of this study was to identify the socioeconomic conditions and
      clinical history of ankylosing spondylitis patients in Switzerland. Data
      collected from 1177 ankylosing spondylitis patients, through a mail-in
      questionnaire, was analyzed for epidemiological factors, clinical presentation,
      musculoskeletal related surgical history and socioeconomic impact. The results
      showed that the sex ratio, average age at onset of symptoms, latent period until
      diagnosis, signs and symptoms, peripheral joint involvement and the prevalence of
      extraarticular organ affection of our patient group all conform with the majority
      of the published literature. Conversely, most reports suggest a higher frequency
      of musculoskeletal surgery, yet a lower employment capacity than the Swiss
      cohort. As described in other publications, aggressive physiotherapy appeared to
      be linked to a reduction in long-term disability, musculoskeletal deformities and
      surgical intervention. It was concluded that the present cohort of ankylosing
      spondylitis patients underwent fewer surgeries for musculoskeletal deformities
      and represented a lower socioeconomic burden (relative to disability and
      inability to work) than most patient populations previously studied.

PMID- 16896360
TI  - Review of chronic low back pain of facet joint origin.
AB  - Chronic low back pain secondary to involvement of the facet joints is a common
      problem. Facet joints have been recognized as potential sources of back pain
      since 1911. Multiple authors have described distributions of pain patterns of
      facet joint pain. The facet joints are paired diarthrodial articulations between
      the posterior elements of the adjacent vertebrae. Lumbar facet joints are
      innervated by medial branches of the dorsal rami of the spinal nerves from the L1
      to L4 levels. At L5, the dorsal ramus travels between the ala of the sacrum and
      its superior articular process and divides into medial and lateral branches at
      the caudal edge of the process. Each segmental medial branch of the dorsal ramus
      supplies at least two facet joints. The existence of lumbar facet joint pain
      claims has a preponderance of evidence, even though there are a few detractors.
      Multiple studies utilizing controlled diagnostic blocks have established the
      prevalence of lumbar facet joint involvement in patients with chronic low back
      pain, as ranging from 15% to 52%, based on type of population and setting
      studied. Long-term therapeutic benefit has been reported from three types of
      interventions in managing lumbar facet joint pain, including intraarticular
      injections, medial branch blocks and neurolysis of medial branches. This review
      will discuss chronic low back of facet joint origin and covers anatomy,
      pathophysiology, diagnosis, and various aspects related to treatment, including
      clinical effectiveness, cost effectiveness, technical aspects and complications.

PMID- 16896362
TI  - Prevalence of opioid abuse.

PMID- 16896361
TI  - An algorithm for understanding spine imaging.
AB  - The presentation of a patient with primary spine pathology may be confounded by a
      myriad of symptoms that span many organ systems. Likewise, imaging findings are
      often diverse and may be as subtle as slight posterior joint asymmetry combined
      with paravertebral myofascial strain or as goss as fracture-dislocation with
      neurological sequelae. A systematic approach to selecting and applying the
      appropriate imaging study combined with a careful clinical history and
      examination will insure a more accurate diagnosis and proper treatment. The
      biomechanics of injury and the pathophysiology of the disease process in question
      should always be considered. This review discussed an algorithmic approach for
      understanding spine imaging with discussions of radiography, radionuclide scan,
      myelography, computed tomography scanning and magnetic resonance imaging.

PMID- 16896363
TI  - Opioid abuse in interventional pain medicine.

PMID- 16896365
TI  - P53 codon 11, 72, and 248 gene polymorphisms in endometriosis.
AB  - OBJECTIVE: Mutated p53 gene is related to the instability of cell growth and cell
      cycle progression. We aimed to evaluate the association between endometriosis and
      p53 codon 11, 72 and 248 gene polymorphisms. PATIENTS AND METHODS: Women were
      divided into two groups: (1) moderate/severe endometriosis (n=148), and (2) non
      endometriosis groups (n=150). P53 gene polymorphisms include codon11 Glu/Gln or
      Lys (GAG->CAG or AAG), codon 72 Arg/Pro (CGC->CCC), and codon 248 Arg/Thr (CGG
      >TCG). These gene polymorphisms were amplified by polymerase chain reaction and
      detected by electrophoresis after restriction enzyme (Taq I, BstU I, Hap II)
      digestions. Associations between the endometriosis and p53 polymorphisms were
      evaluated. RESULTS: The distributions of p53 codon 72 polymorphisms in both
      groups were significantly different. The proportions of Arg
      homozygotes/heterozygotes/Pro homozygotes in both groups were 9.5/66.2/24.3% and
      30.7/50/19.3%. The proportions of Arg/Pro alleles were 42.6/57.4% and 56/44%. The
      distributions of p53 codon 11 and 248 polymorphisms in both groups were non
      significantly different. All individuals appeared the wild genotypes (Glu11 and
      Arg248 homozygotes). CONCLUSION: Association between endometriosis and p53 codon
      72 polymorphism exists. P53 codon 72*Pro-related genotype and allele are related
      with higher susceptibility of endometriosis. P53 codon 11 and 248 polymorphisms
      are not related with endometriosis susceptibility.

PMID- 16896367
TI  - Ellipsis and discourse coherence.
AB  - VP-ellipsis generally requires a syntactically matching antecedent. However, many
      documented examples exist where the antecedent is not appropriate. Kehler (2000,
      2002) proposed an elegant theory which predicts a syntactic antecedent for an
      elided VP is required only for a certain discourse coherence relation
      (resemblance) not for cause-effect relations. Most of the data Kehler used to
      motivate his theory come from corpus studies and thus do not consist of true
      minimal pairs. We report five experiments testing predictions of the coherence
      theory, using standard minimal pair materials. The results raise questions about
      the empirical basis for coherence theory because parallelism is preferred for all
      coherence relations, not just resemblance relations. Further, strict identity
      readings, which should not be available when a syntactic antecedent is required,
      are influenced by parallelism per se, holding the discourse coherence relation
      constant. This draws into question the causal role of coherence relations in
      processing VP ellipsis.

PMID- 16896366
TI  - Does WAVE1 contain a GoLoco/GPR motif?

PMID- 16896368
TI  - Commentary on: "The future of health care in Canada".

PMID- 16896370
TI  - Dutch higher court places further limitations on physician-assisted death.

PMID- 16896369
TI  - Creating an integrated public sector? Labour's plans for the modernisation of the
      English health care system.
AB  - The current Labour Government has embarked on radical public sector reform in
      England. A so-called 'Modernisation Agenda' has been developed that is
      encapsulated in the NHS Plan--a document that details a long-term vision for
      health care. This plan involves a five-fold strategy: investment through greater
      public funding; quality assurance; improving access; service integration and
      inter-professional working; and providing a public health focus. The principles
      of Labour's vision have been broadly supported. However, achieving its aims
      appears reliant on two key factors. First, appropriate resources are required to
      create capacity, particularly management capacity, to enable new functions to
      develop. Second, promoting access and service integration requires the
      development of significant co-ordination, collaboration and networking between
      agencies and individuals. This is particularly important for health and social
      care professionals. Their historically separate professions suggest that a
      significant period of change management is required to allow new roles and
      partnerships to evolve. In an attempt to secure delivery of its goals, however,
      the Government has placed the emphasis on further organisational restructuring.
      In doing so, the Government may have missed the key challenges faced in
      delivering its NHS Plan. As this paper argues, cultural and behavioural change is
      probably a far more appropriate and important requirement for success than a
      centrally directed approach that emphasises the rearrangement of structural
      furniture.

PMID- 16896371
TI  - Looking back from 2015.

PMID- 16896372
TI  - Stroke service in The Netherlands: an exploratory study on effectiveness, patient
      satisfaction and utilisation of healthcare.
AB  - OBJECTIVE: To assess whether shared care for stroke patients results in better
      patient outcome, higher patient satisfaction and different use of healthcare
      services. DESIGN: Prospective, comparative cohort study. SETTING: Two regions in
      The Netherlands with different healthcare models for stroke patients: a shared
      care model (stroke service) and a usual care setting. PATIENTS: Stroke patients
      with a survival rate of more than six months, who initially were admitted to the
      Stroke Service of the University Hospital Maastricht (experimental group) in the
      second half of 1997 and to a middle sized hospital in the western part of The
      Netherlands between March 1997 and March 1999 (control group). MAIN OUTCOME
      MEASURES: Functional health status according to the SIP-68, EuroQol, Barthel
      Index and Rankin Scale, patient satisfaction and use of healthcare services.
      RESULTS: In total 103 patients were included in this study: 58 in the
      experimental group and 45 in the control group. Six months after stroke, 64% of
      the surviving patients in the experimental group had returned home, compared to
      42% in the control group (p<0.05). This difference could not be explained by
      differences in health status, which was comparable at that time. Patients in the
      shared care model scored higher on patient satisfaction, whereas patients in the
      usual care group received a higher volume of home care. CONCLUSIONS: The Stroke
      Service Maastricht resulted in a higher number of patients who returned home
      after stroke, but not in a better health status. Since patients in the usual care
      group received a higher volume of healthcare in the period of rehabilitation, the
      Stroke Service Maastricht might be more efficient.

PMID- 16896373
TI  - Participation of general practitioners in disease management: experiences from
      The Netherlands.
AB  - OBJECTIVE: To investigate the extent to which GPs in The Netherlands participate
      in disease management and how personal opinions, impeding and promoting
      incentives as well as physician characteristics influence their attitude towards
      disease management. METHODS: The attitude-model of Fishbein and Ajzen was used to
      describe the attitude of GPs towards disease management and main influencing
      factors. After interviewing seventeen representatives of the GPs and testing a
      questionnaire, the final questionnaire was sent to all GPs in The Netherlands
      (7680 GPs) barring those involved in the testing of the questionnaire. RESULTS:
      At least 10.4% of all Dutch GPs are active in disease management. The main
      factors predicting a positive attitude towards disease management are the
      following: GPs' opinion that they are improving quality and efficiency of care
      when executing disease management, presence of a good quality network between
      actors involved prior to the start of disease management, working in a health
      centre, and performing sideline activities besides their daily activities as GPs.
      The main factors predicting a negative attitude are: GPs' opinion that the
      investment-time is too high, lack of reimbursement for disease management
      activities, working in a solo practice, and not performing any sideline
      activities beside their daily activities as GP. CONCLUSIONS: The factors
      predicting a negative attitude of Dutch GPs towards disease management dominate
      the factors predicting a positive attitude. The arguments in favour of disease
      management are matters of belief, for example concerning improvements in the
      quality of care, while arguments against are more concrete barriers e.g. high
      workload and financial reimbursement. Placed on the innovation timeline, the
      10.4% participation might be taken to represent the start of a trend.

PMID- 16896375
TI  - Do NHS walk-in centres in England provide a model of integrated care?
AB  - PURPOSE: To undertake a comprehensive evaluation of NHS walk-in centres against
      criteria of improved access, quality, user satisfaction and efficiency. CONTEXT:
      Forty NHS walk-in centres have been opened in England, as part of the UK
      governments agenda to modernise the NHS. They are intended to improve access to
      primary care, provide high quality treatment at convenient times, and reduce
      inappropriate demand on other NHS providers. Care is provided by nurses rather
      than doctors, using computerised algorithms, and nurses use protocols to supply
      treatments previously only available from doctors. DATA SOURCES: Several linked
      studies were conducted using different sources of data and methodologies. These
      included routinely collected data, site visits, patient interviews, a survey of
      users of walk-in centres, a study using simulated patients to assess quality of
      care, analysis of consultation rates in NHS services near to walk-in centres, and
      audit of compliance with protocols. CONCLUSION & DISCUSSION: The findings
      illustrate many of the issues described in a recent WHO reflective paper on
      Integrated Care, including tensions between professional judgement and use of
      protocols, problems with incompatible IT systems, balancing users' demands and
      needs, the importance of understanding health professionals' roles and issues of
      technical versus allocative efficiency.

PMID- 16896374
TI  - Breaks in continuity of care and the rural senior transferred for medical care
      under regionalisation.
AB  - Continuity of care, defined as the patient experiencing coherent care over time
      and place, is challenged when a rural senior with multiple medical problems is
      transferred to a regional hospital for acute care. From an illustrative case of
      an older patient with pneumonia and atrial fibrillation, we catalogue potential
      breaks in continuity of care. Optimal continuity of care is characterised not
      only by regular contact with the providers who establish collaboration with
      patients and their caregivers, but also by communication, co-ordination,
      contingency, convenience, and consistency. Because it is not possible to have the
      same providers continuously available (relational continuity), for continuity of
      care, there is a need for integrative system approaches, such as: (1) policy and
      standards, disease management programs, integrated clinical pathways (management
      continuity), (2) electronic health information systems and telecommunications
      technology (communication continuity). The evaluation of these approaches
      requires measures that account for the multi-faceted nature of continuity of
      care.

PMID- 16896376
TI  - PRISMA: a new model of integrated service delivery for the frail older people in
      Canada.
AB  - PURPOSE: PRISMA is an innovative co-ordination-type Integrated Service Delivery
      System developed to improve continuity and increase the efficacy and efficiency
      of services, especially for older and disabled populations. DESCRIPTION: The
      mechanisms and tools developed and implemented by PRISMA include: (1) co
      ordination between decision-makers and managers, (2) a single entry point, (3) a
      case management process, (4) individualised service plans, (5) a single
      assessment instrument based on the clients' functional autonomy, and (6) a
      computerised clinical chart for communicating between institutions for client
      monitoring purposes. PRELIMINARY RESULTS: The efficacy of this model has been
      tested in a pilot project that showed a decreased incidence of functional
      decline, a decreased burden for caregivers and a smaller proportion of older
      people wishing to be institutionalised. CONCLUSION: The on-going implementation
      and effectiveness study will show evidence of its real value and its impact on
      clienteles and cost.

PMID- 16896377
TI  - Do integrated mental healthcare organisations facilitate process quality in the
      treatment of people with schizophrenia and related psychoses?
AB  - OBJECTIVE: The objective of this study is to investigate the influence of mergers
      of ambulatory and mental healthcare organisations on the process quality of care
      for persons suffering from schizophrenia or related psychoses. THEORY: On the
      basis of the theory of Donabedian we assume the relationships between three types
      of quality in healthcare: structure quality, process quality and outcome quality.
      This study focuses on the influences of structure quality, i.e. years since
      merger and catchment area size upon process quality. METHODS: Criteria according
      to Tugwell for evaluating healthcare were used to describe the process quality of
      schizophrenia care, resulting in a process quality questionnaire with 6 subscales
      and 21 items. Leading psychiatrists of 31 Dutch mental healthcare organisations,
      covering 89% of the country, answered the questionnaire. Both programmes and
      documents from the responding institutions and schizophrenia projects were
      analysed. Correlations of two determinants, age of the merged organisation and
      catchment area size, were made with total scale scores and the sub scores of the
      questionnaire. RESULTS: The response rate was 97% (31/32). Twenty-two
      organisations (71%) had a score of more than 50% on the used scale, 8 (29%)
      scored less. Two evidence-based interventions were implemented in more than 50%
      of the organisations, three in less than 50%. A low degree of implementation
      occurs in establishing care for people with schizophrenia from ethnic minorities,
      standardising diagnostic procedures and continuity of care. No significant
      relationship between the age of the merged organisation ('age') and the total
      process quality of schizophrenia care was found, however, the relationships
      between age and the subscales availability of interventions and integrated
      treatment were significant. No association was found between the size of the
      MHO's catchment area and any of the used subscales. CONCLUSIONS: The age of
      integration of residential and ambulatory mental health institutions correlates
      significantly with two subscales of process quality of schizophrenia care, i.e.
      availability of interventions and treatment. Catchment area size is not
      significantly associated with process quality or any of the subscales. Despite
      the mentioned positive effects, the overall picture of schizophrenia care is not
      very positive. Additional forces other than merely integration of ambulatory and
      residential services are needed for the further implementation of evidence-based
      interventions, diagnostic standards and continuity of care. The development of a
      national 'schizophrenia standard' (like in other countries) in relation with
      implementation plans and strategies to evaluate care on a regional level is
      recommended as well as further research on patient outcomes in relation to
      mergers of mental healthcare organisations.

PMID- 16896378
TI  - Does scarcity lead to better integrated care?

PMID- 16896379
TI  - Consumer-directed services: lessons and implications for integrated systems of
      care.
AB  - Over the past decade, policy makers in developed countries have begun to pay
      increasing attention to reform of the long-term care system for the frail elderly
      and younger people with disabilities. A continuum of strategies have generated
      interest, including integrated systems of care with agency/professionally managed
      service packages on the one end, and programs offering cash benefits along with
      the flexibility to decide how to best use these funds to meet individual needs
      and preferences, on the other. The latter approach, known as "consumer-directed
      care," is found in various forms and degrees in Europe and North America.
      Primarily organised around the provision of home and community care, consumer
      directed services are aimed at empowering clients and family carers, giving them
      major control over the what, who and when of needed care. Consumer-directed care
      appears to be the antithesis of integrated care. However, it actually holds
      important lessons and implications for the latter. This policy paper explores the
      rationale and models of consumer-directed services at home, reviews developments,
      designs and outcomes of programs in the Austria, Germany, The Netherlands, and
      the US. It also discusses how this experience could be helpful in shaping better
      and more responsive integrated models of care for vulnerable long term care
      populations.

PMID- 16896380
TI  - Vertical integration and contractual network in the cardiovascular sector: the
      experience of the Italian region Emilia Romagna.
AB  - OBJECTIVE: We analysed the integrated planning model adopted by the Italian
      region Emilia Romagna in year 2000 to cover the entire range of treatment of
      cardiovascular disease. This model, called "hub and spoke", provides for the
      transfer of patient care and treatment from peripheral units (the spokes) to
      central units (the hubs) once a certain complexity threshold has been reached.
      METHODS: We examined inter-temporal variations in patients flows for the
      selection/referral and follow-up phases between cardiac surgery and cardiology
      units during two periods characterised by different organisational set-ups, in
      order to reflect on the progress being made in the organisation of the network.
      The database consisted of regional records of hospital discharges during the 1997
      2001 period. RESULTS: The investigation pointed to the achievement of a good
      degree of coordination between structures at different levels of specialisation
      in the case of cardiac surgery, for which six centres were selected already in
      1996. On the other hand, the more recent introduction of a hierarchical system
      for interventional cardiology points to the prevalence of operations on patients
      previously treated within the same centre, to admissions by direct access, and to
      follow-up mainly conducted within the hub providing the initial service.
      CONCLUSIONS: Despite the progress made towards the more effective rationalisation
      of the health care network, there is still room for improvement in relations
      between different centres, in particular with regard to the clearer definition of
      the roles and interdependence of those intermediate-level centres located between
      the hub centres and basic healthcare facilities.

PMID- 16896381
TI  - End-of-life care in the United States: policy issues and model programs of
      integrated care.
AB  - BACKGROUND: End-of-life care financing and delivery in the United States is
      fragmented and uncoordinated, with little integration of acute and long-term care
      services. OBJECTIVE: To assess policy issues involving end-of-life care,
      especially involving the hospice benefit, and to analyse model programs of
      integrated care for people who are dying. METHODS: The study conducted structured
      interviews with stakeholders and experts in end-of-life care and with
      administrators of model programs in the United States, which were nominated by
      the experts. RESULTS: The two major public insurance programs--Medicare and
      Medicaid--finance the vast majority of end-of-life care. Both programs offer a
      hospice benefit, which has several shortcomings, including requiring physicians
      to make a prognosis of a six month life expectancy and insisting that patients
      give up curative treatment--two steps which are difficult for doctors and
      patients to make--and payment levels that may be too low. In addition, quality of
      care initiatives for nursing homes and hospice sometimes conflict. Four
      innovative health systems have overcome these barriers to provide palliative
      services to beneficiaries in their last year of life. Three of these health
      systems are managed care plans which receive capitated payments. These providers
      integrate health, long-term and palliative care using an interdisciplinary team
      approach to management of services. The fourth provider is a hospice that
      provides palliative services to beneficiaries of all ages, including those who
      have not elected hospice care. CONCLUSIONS: End-of-life care is deficient in the
      United States. Public payers could use their market power to improve care through
      a number of strategies.

PMID- 16896382
TI  - Direct payment is a healthy option.

PMID- 16896383
TI  - Linking up with the community: a fertile strategy for a university hospital?
AB  - PURPOSE: To systematically identify, describe and characterise the collaborative
      initiatives, which have been established between the Academic Medical
      Centre/University of Amsterdam and local health care providers in the adjacent
      community. BACKGROUND: The viability of university hospitals is jeopardised.
      Their narrowed orientation on delivering the most advanced services to the
      sickest patients challenges their missions in patient care, science and
      education. By linking up with local health care providers, university hospitals
      create synergistic relationships that should secure these three academic missions
      for the future. METHODS: We conducted a multiple case study in two stages.
      Initially, division leaders and the director of integrated care were consulted to
      identify all existing collaborative initiatives of the Academic Medical Centre.
      Successively, face-to-face interviews were held with the leaders of these
      initiatives. During these interviews data were primarily collected through a
      questionnaire. Notes of the interviewer, and documents (if available) were also
      collected. The analysis focused on systematically describing and characterising
      the initiatives using the concept of 'community-based integrated care'. RESULTS:
      Twenty-seven heterogeneous initiatives were identified. Half of these initiatives
      are targeted to the adjacent community of the Academic Medical Centre, but only
      four of them are initiated on the basis of community information and involve the
      community and/or patients. Furthermore, the extent of integration differed per
      dimension. Functional integration within the initiatives has been relatively low,
      clinical integration mixed, and professional integration quite advanced.
      CONCLUSIONS: The results indicate that a considerable number of collaborative
      initiatives have emerged. Still, these initiatives are loosely 'community-based'
      and hardly focus on the full integration of care services. This suggests that the
      community linkages of the Academic Medical Centre in Amsterdam could be further
      developed by gaining the full support of all clinical departments for the
      strategic approach and by adapting an overall hospital perspective to monitor the
      progress towards community-based integrated care.

PMID- 16896384
TI  - Deinstitutionalisation of mental health care in The Netherlands: towards an
      integrative approach.
AB  - OBJECTIVE: The objective of this policy paper is to put recent developments in
      Dutch mental health reform in an international perspective and draw conclusions
      for future directions in policy. CONTEXT OF THE CASE: The practice of Western
      psychiatry in the second half and particularly in the last decade of the 20th
      century has fundamentally changed. Dutch psychiatry has traditionally been
      prominently bed-based and various policies in the last ten years have been
      intended to reduce the influence of the mental hospitals. Until the mid-1990s,
      this had not resulted in reducing the psychiatric bed rate in comparison to other
      countries. Since then, there have been rapid, dramatic changes. DATA SOURCES: We
      summarised two recent national studies on this subject and placed them in a
      national and international context, using documents on psychiatric reforms,
      government and advisory board reports and reviews on deinstitutionalisation in
      different countries. CASE DESCRIPTION: The practice of psychiatry in the second
      half, and particularly in the last decade, of the 20th century has fundamentally
      changed. This has resulted in a spectacular decline in the number of beds in
      mental hospitals, increased admissions, decreased length of stay, closure of the
      large asylums and in community treatment away from asylums and in society,
      although this is a reform process. This article examines how the Dutch mental
      health care system has developed at the national level. The main topics cover the
      size, nature, aims and effects of the process of deinstitutionalisation and how
      alternative facilities have been developed to replace the old-fashioned
      institutes. CONCLUSIONS AND DISCUSSION: There are two contrasting aspects of
      deinstitutionalisation in Dutch mental health care: the tendency towards
      rehospitalisation in relation to the sudden, late, but rapid reduction of the old
      mental hospitals and their premises; and a relatively large scale for community
      based psychiatry in relation to building mental health care centres. Compared to
      other countries the bed rate in The Netherlands is still among the highest,
      although it is rapidly decreasing. Lessons from psychiatric reform in other
      countries emphasise the counterpart of deinstitutionalisation, especially issues
      such as the quality of alternative community treatment and increasing compulsory
      admission, while the closing down of old mental hospitals has caused a decrease
      in the availability of beds. In The Netherlands less attention has been paid to
      legislation, societal attitudes towards psychiatry, the roles of other care
      suppliers, the balancing and financing of care, the fate of psychiatric patients
      from old hospitals, the way to cope with the ever-increasing demand for
      psychiatric help and the actual quality of psychiatric help. A more integrative
      policy that includes all these aspects is desirable.

PMID- 16896386
TI  - The future of integrated primary care: community health centres at the heart of
      the neighbourhood.

PMID- 16896385
TI  - Integration between general practice and mental health services in Italy:
      guidelines for consultation-liaison services implementation.
AB  - PURPOSE: This paper illustrates some guidelines for the implementation of
      Consultation-liaison services in contexts where GPs work alone. We present some
      activity data of our experience in the period 1999-2004 and a critical evaluation
      of what works and what does not work. CONTEXT: In Italy single-sited spontaneous
      initiatives of co-operation and integration between general practice and
      psychiatry have been implemented in many regions. Recently, the Italian Health
      Care Government has begun to encourage integration between primary and secondary
      care for the management of mental health. The Bologna Consultation-liaison
      Service opened in 1999 in one area. The service was first located in the
      Community Mental Health Centre and subsequently in a medical non-psychiatric
      outpatient service. In 2002, the services were implemented in the overall city
      area, and the Bologna Consultation-liaison Service had its own office in the
      centre of the town. DATA SOURCE: Data have been collected by reviewing clinical
      charts. They include clinical (mental status examination, progress notes) and
      socio-demographic data, assessment scales that measure psychological distress and
      disability, reports for GPs, and consultation outcome. CONCLUSION: A consultation
      liaison service like the one proposed in this paper could contribute to an
      efficient and fully-integrated collaborative management of common psychiatric
      disorders, reducing the use of mental health services.

PMID- 16896387
TI  - The association between care co-ordination and emergency department use in older
      managed care enrollees.
AB  - OBJECTIVE: To investigate the association between care co-ordination and use of
      the Emergency Department (ED) in older managed care enrollees. DESIGN: Nested
      case-control with 103 cases (used the ED) and 194 controls (did not use the ED).
      PATIENTS AND METHODS: Older patients with multiple chronic illnesses enrolled in
      a care management programme of a large group-model health maintenance
      organisation with more than 50,000 members over the age of 64. Better care co
      ordination was defined as timely follow-up after a change in treatment; fewer
      decision-makers involved with the care plan; and a higher patient-perceived
      rating of overall care co-ordination. Logistic regression was used to assess the
      relationship between ED use (the outcome variable) and measures of care co
      ordination (the predictor variables). RESULTS: Self-reported care co-ordination
      was not significantly different between cases and controls for any of the four
      classifications of inappropriate ED use. Similarly, no differences were found in
      the number of different physicians or medication prescribers involved in the
      patients' care. Four-week follow-up after potentially high-risk events for
      subsequent ED use, including changes in chronic disease medications, missed
      encounters, and same day encounters, did not differ between subjects with
      inappropriate ED use and controls. CONCLUSION: Existing measures of care co
      ordination were not associated with inappropriate ED use in this study of older
      adults with complex care needs. The absence of an association may, in part, be
      attributable to the paucity of validated measures to assess care co-ordination,
      as well as the methodological complexity inherent in studying this topic. Future
      research should focus on the development of new measures and on approaches that
      better isolate the role of care co-ordination from other potential variables that
      influence utilisation.

PMID- 16896388
TI  - Evaluation of the effect of co-financing on collaboration between health care,
      social services and social insurance in Sweden.
AB  - In this paper, we present an ongoing research project aimed to determine the
      impact of co-financing on collaboration around patients with musculoskeletal
      disorders. A trial legislation that allows the social insurance, social services
      and health care services to unite in co-financing under joint political steering
      has been tested in different areas in Sweden. In a series of studies, we compare
      collaboration processes and health outcome for patients with musculoskeletal
      disorders between health centres with co-financing projects and control health
      centres without co-financing projects. In this paper the studies are described
      and some preliminary results are discussed.

PMID- 16896389
TI  - Integrated care: meaning, logic, applications, and implications--a discussion
      paper.
AB  - Integrated care is a burgeoning field. As is often the case in new areas of
      inquiry and action, conceptual clarification is demanded. Without such attention,
      it would be difficult to advance theory and practice in this increasingly
      important professional arena. In the following discussion paper, the authors
      explore the intellectual territory of integrated care, and underscore the need
      for a patient-centric imperative and meaning. They also examine the practical
      applications and implications arising from their views. The intention is to
      stimulate fruitful dialogue and debate about what 'integrated care' could and
      should be.

PMID- 16896391
TI  - Integrated care cannot flourish with broken windows.

PMID- 16896392
TI  - Development and testing of a measure designed to assess the quality of care
      transitions.
AB  - BACKGROUND: To improve the quality of care delivered to older persons receiving
      care across multiple settings, interventions are needed. However, the absence of
      a patient-centred measure specifically designed to assess this care has
      constrained innovation. OBJECTIVE: To develop a rigorously designed and tested
      measure, the Care Transition Measure (CTM). SETTING: A large, integrated managed
      care organisation in Colorado with approximately 55,000 members over the age of
      65 years. PARTICIPANTS: Patients 65 years and older who were recently discharged
      from hospital and received subsequent skilled nursing care in a facility or in
      the home. METHODS: Six focus groups of older persons and their caregivers (n=49)
      were established. Standard qualitative analytic techniques were applied to
      written transcripts and four key domains were identified: (1) information
      transfer; (2) patient and caregiver preparation; (3) self-management support; and
      (4) empowerment to assert preferences. Specific CTM items were developed, pilot
      tested, and refined. Psychometric testing, conducted in a different population
      but selected using the same entry criteria (n=60), included content and construct
      validity, intra-item variation, and floor/ceiling properties. RESULTS: Older
      patients and clinicians found the measure to be highly relevant and comprehensive
      (i.e. content validity). Construct validity was assessed by comparing items from
      the CTM to selected items from a measure developed by Hendriks and colleagues
      (Medical Care 2001; 39(3): 270-283). Inter-item Spearman correlations ranged
      0.388-0.594. No significant floor or ceiling effects were detected. CONCLUSIONS:
      The CTM was developed with substantial input from older patients and their
      caregivers. Psychometric testing suggested that the measure was valid. The CTM
      may serve to fill an important gap in health system performance evaluation by
      measuring the quality of care delivered across settings.

PMID- 16896393
TI  - Integrated care in an international perspective.

PMID- 16896390
TI  - Statistical significant change versus relevant or important change in (quasi)
      experimental design: some conceptual and methodological problems in estimating
      magnitude of intervention-related change in health services research.
AB  - This paper aims to identify problems in estimating and the interpretation of the
      magnitude of intervention-related change over time or responsiveness assessed
      with health outcome measures. Responsiveness is a problematic construct and there
      is no consensus on how to quantify the appropriate index to estimate change over
      time between baseline and post-test designs. This paper gives an overview of
      several responsiveness indices. Thresholds for effect size (or responsiveness
      index) interpretation were introduced some thirty years ago by Cohen who
      standardised the difference-scores (d) with the pooled standard deviation
      (d/SD(pooled)). However, many effect sizes (ES) have been introduced since
      Cohen's original work and in the formula of one of these ES, the mean change
      scores are standardised with the SD of those change scores (d/SD(change)). When
      health outcome questionnaires are used, this effect size is applied on a wide
      scale and is represented as the Standardized Response Mean (SRM). However, its
      interpretation is problematic when it is used as an estimate of magnitude of
      change over time and interpreted with the thresholds, set by Cohen for effect
      size (ES) which is based on SD(pooled). Thus, in the case of using the SRM,
      application of these well-known cut-off points for pooled standard deviation
      units namely: 'trivial' (ES < 0.20), 'small' (ES > or = 0.20 < 0.50), 'moderate'
      (ES > or = 0.50 < 0.80), or large (ES > or = 0.80), may lead to over- or
      underestimation of the magnitude of intervention-related change over time due to
      the correlation between baseline and outcome assessments. Consequently, taking
      Cohen's thresholds for granted for every version of effect size indices as
      estimates of intervention-related magnitude of change, may lead to over- or
      underestimation of this magnitude of intervention-related change over time.

PMID- 16896394
TI  - Quality of regional individual needs assessment agencies regulating access to
      long term-care services: a client perspective.
AB  - PURPOSE: To determine if and how the outcome quality from a client perspective is
      related to process characteristics and structure of Regional Individual Needs
      Assessment Agencies (RIOs) regulating access to long-term care services in The
      Netherlands. THEORY: Because of decentralised responsibilities, ultimo 1999 85
      RIOs were set up. RIOs differ in their structural and process characteristics.
      This could lead to differences in client quality. Insight into factors relating
      to client quality (e.g. client satisfaction) can improve the needs assessment
      process. METHODS: Eighteen RIOs participated in this study. These RIOs each
      selected 120 clients, filled in forms about their needs assessment procedures and
      sent them a questionnaire assessing judgements, experiences and satisfaction with
      the RIO. RESULTS: We received 1916 RIO-forms and 1062 client questionnaires.
      Eighty-two percent of the clients were satisfied with the RIO, the percentages
      not satisfied clients varied from 10 to 29% among items and working procedures.
      Satisfaction is mostly related to what is actually done for the client.
      Information aspects and providing choices are important determinants of client
      quality with the RIO. CONCLUSION: In improving quality seen from a client
      perspective, one should focus on what is actually done for the client, rather
      than looking at the RIOs structure.

PMID- 16896395
TI  - Finnish care integrated?
AB  - The public Finnish social and health care system has been challenged by the
      economic crisis, administrative reforms and increased demands. Better integration
      as a solution includes many examples, which have been taken to use. The most
      important are the rewritten national and municipals strategies and quality
      recommendations, where the different sectors and the levels of care are seen as
      one entity. Many reorganisations have taken place, both nationally and locally,
      and welfare clusters have been established. The best examples of integrated care
      are the forms of teamwork, care management, emphasis on non-institutional care
      and the information technology.

PMID- 16896396
TI  - Integrated care bridges the care gap.

PMID- 16896397
TI  - Progress in the development of integrated mental health care in Scotland.
AB  - The development of integrated care through the promotion of 'partnership working'
      is a key policy objective of the Scottish Executive, the administration
      responsible for health services in Scotland. This paper considers the extent to
      which this goal is being achieved in mental health services, particularly those
      for people with severe and enduring mental illness. Distinguishing between the
      horizontal and vertical integration of services, exploratory research was
      conducted to assess progress towards this objective by examining how far a range
      of functional activities in Primary Care Trusts (PCTs) and their constituent
      Local Health Care Co-operatives (LHCCs) were themselves becoming increasingly
      integrated. All PCTs in Scotland were surveyed by postal questionnaire, and
      followed up by detailed telephone interviews. Six LHCC areas were selected for
      detailed case study analysis. A Reference Group was used to discuss and review
      emerging themes from the fieldwork. The report suggests that faster progress is
      being made in the horizontal integration of services between health and social
      care organisations than is the case for vertical integration between primary
      health care and specialist mental health care services; and that there are
      significant gaps in the extent to which functional activities within Trusts are
      changing to support the development of integrated care. A number of models are
      briefly considered, including the idea of 'intermediate care' that might speed
      the process of integration.

PMID- 16896398
TI  - Opportunities for and constraints to integration of health services in Poland.
AB  - At the beginning of the article the typologies, expected outcomes and forces
      aiming at health care integration are discussed. Integration is recognised as a
      multidimensional concept. The suggested typologies of integration are based on
      structural configurations, co-ordination mechanisms (including clinical co
      ordination), and driving forces. A review of the Polish experience in
      integration/disintegration of health care systems is the main part of the
      article. Creation of integrated health care management units (ZOZs) in the
      beginning of the 1970s serves as an example of structural vertical integration
      missing co-ordination mechanisms. ZOZs as huge, costly and inflexible
      organisations became subjects of public criticism and discredited the idea of
      health care integration. At the end of the 1980s and in the decade of the 1990s,
      management of public health care was decentralised, the majority of ZOZs
      dismantled, and many health care public providers got the status of independent
      entities. The private sector developed rapidly. Sickness funds, which in 1999
      replaced the previous state system, introduced "quasi-market" conditions where
      health providers have to compete for contracts. Some providers developed
      strategies of vertical and horizontal integration to get a competitive advantage.
      Consolidation of private ambulatory clinics, the idea of "integrated care" as a
      "contracting package", development of primary health care and ambulatory
      specialist clinics in hospitals are the examples of such strategies. The new
      health policy declared in 2002 has recognised integration as a priority. It
      stresses the development of payment mechanisms and information base (Register of
      Health Services--RUM) that promote integration. The Ministry of Health is
      involved directly in integrated emergency system designing. It seems that after
      years of disintegration and deregulation the need for effective integration has
      become obvious.

PMID- 16896400
TI  - Integrated care: a position paper of the WHO European Office for Integrated
      Health Care Services.
AB  - The WHO European Office for Integrated Health Care Services in Barcelona is an
      integral part of the World Health Organizations' Regional Office for Europe. The
      main purpose of the Barcelona office is within the integration of services to
      encourage and facilitate changes in health care services in order to promote
      health and improve management and patient satisfaction by working for quality,
      accessibility, cost-effectiveness and participation. This position paper outlines
      the need for Integrated Care from a European perspective, provides a theoretical
      framework for the meaning of Integrated Care and its strategies and summarizes
      the programmes of the office that will support countries in the WHO European
      Region to improve health services.

PMID- 16896401
TI  - Integrating mental health services: the Finnish experience.
AB  - The aim of this paper is to give a short description of the most important
      developments of mental health services in Finland during the 1990s, examine their
      influences on the organisation and provision of services, and describe shortly
      some national efforts to handle the new situation. The Finnish mental health
      service system experienced profound changes in the beginning of the 1990s. These
      included the integration of mental health services, being earlier under own
      separate administration, with other specialised health services, decentralisation
      of the financing of health services, and de-institutionalisation of the services.
      The same time Finland underwent the deepest economic recession in Western Europe,
      which resulted in cut-offs especially in the mental health budgets. Conducting
      extensive national research and development programmes in the field of mental
      health has been one typically Finnish way of supporting the mental health service
      development. The first of these national programmes was the Schizophrenia Project
      1981-97, whose main aims were to decrease the incidence of new long-term patients
      and the prevalence of old long-stay patients by developing an integrated
      treatment model. The Suicide Prevention Project 1986-96 aimed at raising
      awareness of this special problem and decreasing by 20% the proportionally high
      suicide rate in Finland. The National Depression Programme 1994-98 focused at
      this clearly increasing public health concern by several research and development
      project targeted both to the general population and specifically to children,
      primary care and specialised services. The latest, still on-going Meaningful Life
      Programme 1998-2003 which main aim is, by multi-sectoral co-operation, to improve
      the quality of life for people suffering from or living with the threat of mental
      disorders. Furthermore, the government launched in 1999 a new Goal and Action
      Programme for Social Welfare and Health Care 2000-2003, in which mental health
      has been chosen as one of the eight priority areas.

PMID- 16896403
TI  - Psychiatry and human rights.

PMID- 16896402
TI  - IDN rankings and performance: a comment.

PMID- 16896404
TI  - Supplement: 9th international conference on health promoting hospitals,
      Copenhagen, May 16-18, 2001.

PMID- 16896405
TI  - Integration and the performance of healthcare networks: do integration strategies
      enhance efficiency, profitability, and image?
AB  - PURPOSE: This study examines the integration effects on efficiency and financial
      viability of the top 100 integrated healthcare networks (IHNs) in the United
      States. THEORY: A contingency-strategic theory is used to identify the
      relationship of IHNs' performance to their structural and operational
      characteristics and integration strategies. METHODS: The lists of the top 100
      IHNs ranked in two years, 1998 and 1999, by the SMG Marketing Group were merged
      to create a database for the study. Multiple indicators were used to examine the
      relationship between IHNs' characteristics and their performance in efficiency
      and financial viability. A path analytical model was developed and validated by
      the Mplus statistical program. Factors influencing the top 100 IHNs' images,
      represented by attaining ranking among the top 100 in two consecutive years, were
      analysed. RESULTS AND CONCLUSION: No positive associations were found between
      integration and network performance in efficiency or profits. Longitudinal data
      are needed to investigate the effect of integration on healthcare networks'
      financial performance.

PMID- 16896406
TI  - The development of integrated health care models in Scotland.
AB  - Integrated health care is a key policy aim of Scotland's newly devolved
      government. 'Partnership working' is the mechanism that has been selected to
      achieve this goal. Three illustrative examples of health care integration models
      developed in Scotland are considered; system organisation and structure; Local
      Health Care Co-operatives (LHCCs); and Managed Clinical Networks. Using these
      examples the paper explores the nature of 'partnership' and asks if it can
      deliver integrated care.

PMID- 16896409
TI  - European commission.

PMID- 16896408
TI  - Integrated care across borders: possibilities and complexities.
AB  - The main purpose of this practice paper is to describe and analyse the
      possibilities and complexities of integrated health care across borders. First,
      we portray an ideal scenario for this type of care with a case of patients
      suffering from rheumatoid arthritis and living in the Dutch-Belgian frontier
      area. It shows how cross border care enhances continuity of care/tailor-made care
      and the other way around. Secondly, based on different literature sources, we
      describe actual regulations on health care across borders. We show that these
      regulations can be a major hindrance to integrated care. This raises questions on
      the scope and content of policies directed at both cross border and integrated
      care.

PMID- 16896410
TI  - Long-term care insurance and integrated care for the aged in Japan.
AB  - By the introduction of a public, mandatory program of Long-Term Care Insurance
      (LTCI) on April 1, 2000, Japan has moved towards a system of social care for the
      frail and elderly. The program covers care that is both home-based and
      institutional. Fifty percent of the insurance is financed from the general tax
      and the other fifty percent from the premiums of the insured. The eligibility
      process begins with the individual or his/her family applying to the insurer
      (usually municipal government). A two-step assessment process to determine the
      limit of benefit follows this. The first step is an on-site assessment using a
      standardised questionnaire comprising 85 items. These items are analysed by an
      official computer program in order to determine either the applicant's
      eligibility or not. If the applicant is eligible it determines which of 6 levels
      of dependency is applicable. The Japanese LTCI scheme has thus formalised the
      care management process. A care manager is entrusted with the entire
      responsibility of planning all care and services for individual clients. The
      introduction of LTCI is introducing two fundamental structural changes in the
      Japanese health system; the development of an Integrated Delivery System (IDS)
      and greater informatisation of the health system.

PMID- 16896411
TI  - Organisational design for an integrated oncological department.
AB  - OBJECTIVE: The outcomes of a Strength, Weakness, Opportunities and Threat (SWOT)
      analysis of three Integrated Oncological Departments were compared with their
      present situation three years later to define factors that can influence a
      successful implementation and development of an Integrated Oncological Department
      in- and outside (i.e. home care) the hospital. RESEARCH DESIGN: Comparative
      Qualitative Case Study. METHODS: Auditing based on care-as-usual norms by an
      external, experienced auditing committee. RESEARCH SETTING: Integrated
      Oncological Departments of three hospitals. RESULTS: Successful multidisciplinary
      care in an integrated, oncological department needs broad support inside the
      hospital and a well-defined organisational plan.

PMID- 16896412
TI  - Factors predicting trust between GPs and OPs.
AB  - PURPOSE: To study possible differences in trust between general practitioners
      (GPs) and occupational physicians (OPs) and the explanatory factors for trust.
      Insight into the factors predicting trust can improve programmes for stimulating
      the co-operation of GPs and OPs. THEORY: On the basis of theories of trust and of
      social identity theory we expected, (1) in both professions a higher level of
      knowledge-based trust than of identification-based trust, (2) a relationship
      between higher levels of identification-based trust and higher frequency of
      contact, (3) OPs to have a higher level of identification-based trust than GPs.
      We hypothesised (4) that OPs perceiving an equal status have higher levels of
      trust and (5) GPs perceiving a higher status have lower levels of trust. METHODS:
      A mail survey sent to 2297 doctors (1728 GPs and 569 OPs) of which we used 547
      questionnaires. RESULTS: Hypotheses 1 and 2 were supported. Hypothesis 3 was not
      supported. Hypotheses 4 and 5 were supported for knowledge-based trust. On the
      basis of these findings it is possible that co-operation between the two groups
      is still in its early stages. CONCLUSIONS: Programmes to improve the co-operation
      of GPs and OPs should focus on equalising status and stimulating contacts to
      build (identification-based) trust.

PMID- 16896413
TI  - Pastoralist health care in Kenya.
AB  - Health care for the Kenyan pastoralist people has serious shortcomings and it
      must be delivered under difficult circumstances. Often, the most basic
      requirements cannot be met, due to the limited accessibility of health care
      provisions to pastoralists. This adds major problems to the daily struggle for
      life, caused by bad climatic circumstances, illiteracy and poverty. We argue that
      strong, integrated and community based primary health care could provide an
      alternative for these inadequacies in the health system. The question then is how
      primary health care, which integrates a diversity of basic care provisions, such
      as pharmaceutical provision, child delivery assistance, mother and childcare and
      prevention activities, can be implemented. In our view, an appropriate mix of
      decentralisation forms, warranting better conditions on the one hand and relying
      on the current community and power structures and culture on the other hand,
      would be the best solution for the time being.

PMID- 16896415
TI  - From shared care to disease management: key-influencing factors.
AB  - BACKGROUND: In order to improve the quality of care of chronically ill patients
      the traditional boundaries between primary and secondary care are questioned. To
      demolish these boundaries so-called 'shared care' projects have been initiated in
      which different ways of substitution of care are applied. When these projects
      end, disease management may offer a solution to expand the achieved co-operation
      between primary and secondary care. OBJECTIVE: Answering the question: What key
      factors influence the development and implementation of shared care projects from
      a management perspective and how are they linked? THEORY: The theoretical
      framework is based on the concept of the learning organisation. DESIGN: Reference
      point is a multiple case study that finally becomes a single case study. Data are
      collected by means of triangulation. The studied cases concern two interrelated
      Dutch shared care projects for type 2 diabetic patients, that in the end proceed
      as one disease management project. RESULTS: In these cases the predominant key
      influencing factors appear to be the project management, commitment and local
      context, respectively. The factor project management directly links the latter
      two, albeit managing both appear prerequisites to its success. In practice this
      implies managing the factors' interdependency by the application of change
      strategies and tactics in a committed and skillful way. CONCLUSION: Project
      management, as the most important and active key factor, is advised to cope with
      the interrelationships of the influencing factors in a gradually more fundamental
      way by using strategies and tactics that enable learning processes. Then small
      scale shared care projects may change into a disease management network at a
      large scale, which may yield the future blueprint to proceed.

PMID- 16896416
TI  - The long term importance of English primary care groups for integration in
      primary health care and deinstitutionalisation of hospital care.
AB  - PURPOSE: This article reviews the impact of successive experiments in the
      development of primary care organisations in England and assesses the long-term
      importance of English primary care groups for the integration of health and
      community and health and social care and the deinstitutionalisation of hospital
      care. THEORY: Governments in a number of Western countries are attempting to
      improve the efficiency, appropriateness and equity of their health systems. One
      of the main ways of doing this is to devolve provision and commissioning
      responsibility from national and regional organisations to more local agencies
      based in primary care. Such primary care organisations are allocated budgets that
      span both primary and secondary (hospital) services and also, potentially, social
      care. METHOD: This article is based on a systematic review of the literature
      forthcoming from the UK Government's Department of Health-funded evaluations of
      successive primary care organisational developments. These include total
      purchasing pilots, GP commissioning group pilots, personal medical services
      pilots and primary care groups and trusts. RESULTS: Primary care organisations in
      England have proved to be a catalyst in facilitating the development of
      integrated care working between primary and community health services.
      Conversely, primary care organisations have proved less effective in promoting
      integration between health and social care agencies where most progress has been
      made at the strategic commissioning level. The development of primary care trusts
      in England is heralding an end to traditional community hospitals. CONCLUSIONS:
      The development of primary care groups in England are but an intermediate step of
      a policy progression towards future primary care-based organisations that will
      functionally integrate primary and community health services with local authority
      services under a single management umbrella.

PMID- 16896417
TI  - Implementing comprehensive and decentralised health systems: the quest for
      integrated care in post-apartheid South Africa.

PMID- 16896418
TI  - Integrated health care in Russia: to be or not to be?
AB  - The purpose of this paper is to look at what has happened in Russia during the
      last ten years in the health care sector from the point of view of integrated
      care. This country, when it still was the leading subject of the Soviet Union,
      hosted in 1978 the Alma Ata Conference on Primary Health Care, which in many
      countries gave a strong boost on the development of multidisciplinary, community
      based care in a gate-keeper position. In Soviet Russia, PHC became marginalised
      and identical to poor level of care in remote areas of the country where people
      had very little choice and did not want to use it. Has the situation changed, and
      is Russia in practice addressing the problems created by the lack of integration,
      vertical treatment structures and over specialisation? In addition to the data
      sources that are referred to in the text, this paper is based on "gray
      literature" available in project reports and governmental documents, and on the
      personal experiences of the authors, who have worked for long periods of time in
      the Russian Federation as international experts dealing with health sector
      reforms and health policy formulation.

PMID- 16896420
TI  - Integration of services and the European Union: does EU policy make sense?

PMID- 16896421
TI  - Integrated care networks and quality of life: linking research and practice.
AB  - PURPOSE: To report on the development of a project dedicated to improving the
      quality of life of older people through the creation of integrated networks.
      CONTEXT: The project is set within a post-industrial community and against a
      backdrop of government re-organisation and devolution within Wales. The immediate
      research context is determined by utilising an approach to the structure of
      integration derived theoretically. CASE DESCRIPTION: Project CHAIN (Community
      Health Alliances through Integrated Networks) adopts a network perspective as a
      means of addressing both the determinants of health and service delivery in
      health and social care. The Project partners are: healthcare commissioners and
      providers; local authority directorates including community services and
      transportation; the voluntary and private sectors; and a university institute. Co
      opted participants include for a representing older people's interests. DATA
      SOURCES: The Project incorporates an action research method. This paper
      highlights qualitative data elicited from interviews with health and social care
      managers and practitioners. CONCLUSIONS AND DISCUSSION: The Project is ongoing
      and we record progress in building five integrated networks.

PMID- 16896419
TI  - Is there a relationship between service integration and differentiation and
      patient outcomes?
AB  - OBJECTIVE: To examine the level of service integration within Maryland hospitals
      and service differentiation across the hospital system or network and its affect
      on heart failure patient clinical and economic outcomes. DATA SOURCES/STUDY
      SETTING: Maryland Health Services Cost Review Commission Inpatient Data for 1997
      and 1998 were used for secondary data analysis. STUDY DESIGN: Retrospective cross
      sectional. Independent variables were the level of service integration and
      differentiation created from the 1998 American Hospital Association Annual Survey
      based on the work of Bazzoli et al. The primary dependent variables were
      readmission, in-hospital mortality, length of stay and costs. DATA
      COLLECTION/EXTRACTION METHODS: Patients discharged from Maryland hospitals with a
      diagnosis that grouped to DRG 127 (heart failure) were extracted. Multivariate
      linear and logistic models clustered by hospital were used to analyse results at
      the patient level. PRINCIPAL FINDINGS: A higher likelihood of readmission was
      found as the level of Community Differentiation increased. Although costs were
      higher as Total Differentiation increased in 1998, these results were not
      validated by 1997 data. No significant relationship was found between integration
      of services and outcomes. CONCLUSIONS: Similar outcomes were achieved regardless
      of the level of service integration or differentiation. Community hospitals
      produce similar patient outcomes at the same cost for this diagnosis.

PMID- 16896422
TI  - In search of the quickest way to disseminate health care innovations.
AB  - RESEARCH QUESTION: Innovations in health care are slowly disseminated in The
      Netherlands and elsewhere. That's why the researchers defined their research
      question: What is the quickest way of disseminating health care innovations?
      RESEARCH METHOD: The design was a comparative, qualitative case study. The
      researchers invited a group of 52 authors to describe their 21 health care
      innovations. All case descriptions were published in a book of 261 pages.
      RESULTS: Six types of innovations were distinguished. Most innovations
      simultaneously improved quality from the patient's point of view (18 out of 21
      cases), professional pride (18/21) and speed of introduction (16/21). Clinical
      outcomes were better or comparable in 13 of the 21 cases. Brainstorm sessions
      took place with the innovators and the 22 experts on the quickest way to
      disseminate the innovations more widely in The Netherlands. These sessions looked
      for the critical success factors for the dissemination of the 21 projects and
      identified nine. The following factors were identified: 1. A clear distribution
      of responsibilities between professionals within the innovation (20/21). 2.
      Enough educational programs about the innovations for the professionals (18/21).
      3. Adequate ICT support for the running of the innovations (15/21). 4. Suitable
      publicity for the innovations (12/21). 5. An adequate payment system for
      innovative care providers (7/21). 6. The right size of catchment's area for the
      innovations (6/21). 7. Enough professional freedom to adopt the innovation
      (5/21). 8. Fast managerial and public decision-making about the adoption of the
      innovation (3/21). 9. The embedding of the innovations in quality management
      assurance policy (1/21). DISCUSSION: The results of the study had some influence
      on the political health agenda in The Netherlands, leading to greater emphasis on
      innovations and quality of care.

PMID- 16896423
TI  - Chain of care development in Sweden: results of a national study.
AB  - Chains of Care are today an important counterbalance to the ever-increasing
      fragmentation of Swedish health care, and the ongoing development work has high
      priority. Improved quality of care is the most important reason for developing
      Chains of Care. Despite support in the form of goals and activity plans, seven
      out of ten county councils are uncertain whether they have been quite successful
      in the development work. Strong departmentalisation of responsibilities between
      different medical professions and departments, types of responsibilities and
      power still remaining in the vertical organisation structure, together with
      limited participation from the local authorities, are some of the most commonly
      mentioned reasons for the lack of success. Even though there is hesitation
      regarding the development work up to today, all county councils will continue
      developing Chains of Care. The main reason is, as was the case with Chain of Care
      development up to today, to improve quality of care. Although one of the main
      purposes is to make health care more patient-focused, patients in general seem to
      have limited impact on the development work. Therefore, the challenge is to
      design Chains of Care, which regards patients as partners instead of objects.

PMID- 16896424
TI  - Multidisciplinary guidelines in Dutch mental health care: plans, bottlenecks and
      possible solutions.
AB  - PURPOSE: This article describes the Dutch 'Multidisciplinary Guidelines in Mental
      Health Care' project and its first products (multidisciplinary guidelines on
      depressive and anxiety disorders). CONTEXT OF CASE: In the early 1990s,
      disciplines in Dutch mental health care formulated their first monodisciplinary
      guidelines, which disagreed on essential features. In 1998, the Dutch government
      invited representatives of the five core disciplines in mental health care
      (psychiatrists, general practitioners, psychotherapists (clinical), psychologists
      and psychiatric nurses) to start a joint project aimed at the development of new
      integrated multidisciplinary guidelines. DATA SOURCES: The vision document,
      presented in 2000 by the five core disciplines, describes the directions for the
      development of new guidelines. The guidelines on depressive and anxiety disorders
      will appear in 2004. CASE DESCRIPTION: The first draft guidelines were presented
      in May 2003, in line with the vision document (2000). However, it is still not
      certain whether they will be authorised by all professional groups. Some
      disciplines do not recognise themselves in these guidelines. It is argued that
      these problems can be attributed at least in part to the evidence-based method
      that was used in drafting the guidelines. Interventions are compared on the basis
      of their 'level of evidence', the consequence of which is that cognitive
      behavioural therapy and drug treatment are almost always seen as the only
      appropriate interventions. Other interventions are excluded because of their
      lower level of evidence. CONCLUSIONS AND DISCUSSION: The conclusion is that
      guidelines cannot be based on empirical evidence alone. It is argued that the
      collective sense of professions involved should also be integrated into the
      guideline, for example in relation to goal differentiation. It is finally argued
      that multidisciplinary guidelines must also offer a hierarchy between those
      goals, i.e. a vision of the appropriate type of care and the order in which the
      various care components should be administered.

PMID- 16896425
TI  - Comparison of the OxyMask and Venturi mask in the delivery of supplemental
      oxygen: pilot study in oxygen-dependent patients.
AB  - BACKGROUND: The OxyMask (Southmedic Inc, Canada) is a new face mask for oxygen
      delivery that uses a small 'diffuser' to concentrate and direct oxygen toward the
      mouth and nose. The authors hypothesized that this unique design would enable the
      OxyMask to deliver oxygen more efficiently than a Venturi mask (Hudson RCI, USA)
      in patients with chronic hypoxemia. METHODS: Oxygen-dependent patients with
      chronic, stable respiratory disease were recruited to compare the OxyMask and
      Venturi mask in a randomized, single-blind, cross-over design. Baseline blood
      oxygen saturation (SaO2) was established breathing room air, followed in a random
      order by supplemental oxygen through the OxyMask or Venturi mask. Oxygen delivery
      was titrated to maintain SaO2 4% to 5% and 8% to 9% above baseline for two
      separate 30 min periods of stable breathing. Oxygen flow rate, partial pressure
      of inspired and expired oxygen (PO2) and carbon dioxide (PCO2), minute
      ventilation, heart rate, nasal and oral breathing, SaO2 and transcutaneous PCO2
      were collected continuously. The study was repeated following alterations to the
      OxyMask design, which improved clearance of carbon dioxide. RESULTS: Thirteen
      patients, aged 28 to 79 years, were studied initially using the original OxyMask.
      Oxygen flow rate was lower, inspired PO2 was higher and expired PO2 was lower
      while using the OxyMask. Minute ventilation and inspired and expired PCO2 were
      significantly higher while using the OxyMask, whereas transcutaneous PCO2, heart
      rate and the ratio of nasal to oral breathing did not change significantly
      throughout the study. Following modification of the OxyMask, 13 additional
      patients, aged 18 to 79 years, were studied using the same protocol. The modified
      OxyMask provided a higher inspired PO2 at a lower flow rate, without evidence of
      carbon dioxide retention. CONCLUSIONS: Oxygen is delivered safely and more
      efficiently by the OxyMask than by the Venturi mask in stable oxygen-dependent
      patients.

PMID- 16896426
TI  - Asthma control in Canada remains suboptimal: the Reality of Asthma Control (TRAC)
      study.
AB  - BACKGROUND: Two Canadian studies showed that 55% of patients with asthma had
      daily symptoms (in 1996) and that 57% of patients suffered from poorly controlled
      asthma (in 1999). OBJECTIVES: To assess the state of asthma control of adult
      Canadians, and asthma knowledge and practices of Canadian physicians actively
      involved in the care of patients with asthma. METHODS: Telephone interviews were
      conducted with adults 18 to 54 years of age who had been diagnosed with asthma at
      least six months before the survey, who did not have chronic obstructive
      pulmonary disease and who had a smoking history of fewer than 20 pack-years.
      Physicians were surveyed by telephone and mail. The surveys took place between
      April and August 2004. RESULTS: Almost all (97%) of the 893 patients believed
      that they had controlled asthma; however, only 47% had controlled disease
      according to symptom-based guideline criteria. Just 39% of 463 physicians based
      their treatment recommendations on the Canadian asthma guidelines most or all of
      the time, despite having a high awareness of them. Only 11% of patients had
      written action plans, and one-half of patients with action plans did not use them
      regularly. Almost three-quarters of patients expressed concerns about taking
      inhaled corticosteroids. CONCLUSIONS: Since the last major national survey,
      guideline implementation has not resulted in significant changes in asthma
      related morbidity. Effective means of knowledge transfer should be developed and
      implemented to improve the translation of guideline recommendations into care.

PMID- 16896427
TI  - Ozone--42 years later.

PMID- 16896428
TI  - Smoking inside Canadian acute care hospitals.
AB  - OBJECTIVE: To assess smoking policies at Canadian acute care hospitals. METHOD: A
      questionnaire was designed, piloted and faxed to all acute care hospitals in
      Canada. The questionnaire was designed to address the following: what is the
      current policy regarding patient smoking? Are staff and/or visitors allowed to
      smoke inside the hospital? Is there a separate policy for psychiatric patients?
      Are smoking cessation products available at the hospital pharmacy? Is the policy
      governed by regional or municipal legislation? RESULTS: A total of 852 hospitals
      were included in the study. Of these, 476 responded to the questionnaire, for an
      overall response rate of 56%. Twenty-seven per cent of respondents allowed
      patient smoking inside the hospital. While staff smoking was not allowed inside
      most hospitals (93%), 32% of hospitals in Quebec allowed staff to smoke inside
      the building. Thirty per cent of hospitals had a separate policy for psychiatric
      patients, and 27% of hospitals had provisions for visitor smoking. Sixty-seven
      per cent of hospitals were able to offer patients smoking cessation products
      while they were in hospital. CONCLUSIONS: Many Canadian hospitals continue to
      allow smoking inside their facilities. There is considerable variation in
      hospital smoking policies across the country.

PMID- 16896429
TI  - Progressive dyspnea associated with a crazy-paving appearance on a chest computed
      tomography scan.
AB  - A 'crazy-paving' appearance of the lungs on computed tomography scanning of the
      chest was first described nearly 20 years ago in patients with pulmonary alveolar
      proteinosis, and was thought to be characteristic of this condition. However,
      this pattern has subsequently been reported in a variety of pulmonary diseases
      and is now considered to be nonspecific. The present report describes a case of a
      74-year-old man in whom congestive heart failure presented with a crazy-paving
      appearance of the lungs on a chest computed tomography scan. This uncommon
      association illustrates the importance of the correlation of clinical and
      radiographic information.

PMID- 16896430
TI  - Drotrecogin alpha (activated) in two patients with the hantavirus cardiopulmonary
      syndrome.
AB  - Hantavirus cardiopulmonary syndrome (HCPS) is associated with rapid
      cardiopulmonary collapse from endothelial injury, resulting in massive capillary
      leak, shock and severe hypoxemic respiratory failure. To date, treatment remains
      supportive and includes mechanical ventilation, vasopressors and extracorporeal
      membrane oxygenation, with mortality approaching 50%. Two HCPS survivors
      initially given drotrecogin alpha (activated) (DAA) for presumed bacterial septic
      shock are described. Vasoactive medications were required for a maximum of 52 h,
      whereas creatinine levels and platelet counts normalized within seven to nine
      days. Given the similar presentations of HCPS and bacterial septic shock,
      empirical DAA therapy will likely be initiated before a definitive diagnosis of
      HCPS is made. Further observations of DAA in HCPS seem warranted.

PMID- 16896431
TI  - Pneumonia and pleural effusion due to Cryptococcus laurentii in a clinically
      proven case of AIDS.
AB  - Non-neoformans cryptococci were previously considered to be saprophytes and
      nonpathogenic to humans. Cryptococcus laurentii is frequently used as a
      biological means to control fruit rot. Interestingly, C laurentii has recently
      been reported to be a rare cause of infection in humans. The authors report a
      case of pulmonary cryptococcosis caused by C laurentii in a diabetic AIDS patient
      who was on antituberculosis and antiretroviral treatments. The sputum smear
      revealed capsulated yeast cells that were identified as C laurentii. Repeated
      pleural fluid culture revealed growth of C laurentii. Both respiratory samples
      were negative for acid-fast bacilli. Moraxella catarrhalis and Klebsiella
      pneumoniae were also found in the sputum, but not in the pleural fluid. The
      patient had a good response to oral fluconazole therapy at 600 mg/day for five
      weeks and was then discharged. The present article is the first to report on the
      rare pulmonary involvement of C laurentii in the Indian HIV population. These
      unusual forms of cryptococci create a diagnostic predicament in the rapid
      diagnosis of pulmonary cryptococcosis. A high degree of suspicion and improvement
      of techniques for culture and identification will contribute to the early
      diagnosis and treatment of unusual fungal infections.

PMID- 16896432
TI  - Molecular mechanisms of cellular mechanics.
AB  - Mechanical forces play an essential role in cellular processes as input, output,
      and signals. Various protein complexes in the cell are designed to handle,
      transform and use such forces. For instance, proteins of muscle and the
      extracellular matrix can withstand considerable stretching forces, hearing
      related and mechanosensory proteins can transform weak mechanical stimuli into
      electrical signals, and regulatory proteins are suited to forcing DNA into loops
      to control gene expression. Here we review the structure-function relationship of
      four protein complexes with well defined and representative mechanical functions.
      The first example is titin, a protein that confers passive elasticity on muscle.
      The second system is the elastic extracellular matrix protein, fibronectin, and
      its cellular receptor integrin. The third protein system is the transduction
      apparatus in hearing and other mechanical senses, likely containing cadherin and
      ankyrin repeats. The last system is the lac repressor protein, which regulates
      gene expression by looping DNA. This review focuses on atomic level descriptions
      of the physical mechanisms underlying the various mechanical functions of the
      stated proteins.

PMID- 16896433
TI  - Far-infrared spectroscopy of small polycyclic aromatic hydrocarbons.
AB  - Both experimental and theoretical spectroscopic studies on small gas phase
      polycyclic aromatic hydrocarbons in the far-infrared spectral region are
      reported. The experimental set-up based on thermal emission and Fourier transform
      far infrared analysis led to the detection of relatively broad vibrational bands,
      unresolved in rotation, representative of each molecule. Detailed theoretical
      investigations were performed, including both ab initio calculations and spectral
      simulations. For the majority of the samples, this study provides the first
      detection of the vibrational modes associated with the skeleton motions.

PMID- 16896434
TI  - The Ni2+O2 reaction: the IR spectrum and structure of Ni2O2. A combined IR matrix
      isolation and theoretical study.
AB  - The formation of Ni2O2 can be observed from the condensation of effusive beams of
      Ni and O2 in neon or argon matrices. Observation of 58Ni(2)16O2, 58Ni60Ni16O2,
      60Ni2(16)O2, Ni(2)18O2 and Ni(2)16O18O isotopic data for five fundamental
      transitions enable a discussion of structural parameters for matrix-isolated
      Ni2O2 in its cyclic ground state. Analysis of the nickel isotopic effects on the
      58,60Ni2(16)O18O fundamentals suggest an elongated rhombic structure with a Ni-O
      bond force constant (240+/-10 N m-1) and NiONi bond angles around 79 degrees. The
      latter points to a Ni-Ni internuclear distance shorter than the O-O one. Low
      lying singlet, triplet and quintet states have been studied using density
      functional theory with an unrestricted wave function and broken symmetry
      formalism. The high spin states and closed shell singlet states have been also
      investigated at the CCSD(T) level. The Ni2O2 ground state is calculated to be an
      antiferromagnetic singlet state with all the hybrid functionals. The first order
      properties (energies, geometry) calculated with a hybrid functional are very
      similar when different exchange-correlation functionals with different exact
      exchange fractions are used and the calculated ground state geometry (NiONi bond
      angle near 80 degrees, NiO bond distance around 179.5 pm) is in good agreement
      with the experimental estimate. Nevertheless, a correct reproduction of the
      experimental vibrational properties is found only when a hybrid functional
      containing an exact exchange fraction in the 0.4-0.5 range is used. The orbital
      and topological bonding analyses of Ni2O2 reveal that the relatively short Ni-Ni
      internuclear distance within the molecule should not be interpreted as a
      remaining metal-metal bonding interaction, but clearly indicate that the bonding
      driving force is due to the formation of four strong and highly polarized Ni-O
      bonds. Even in such an early stage of metal oxidation, the Ni-Ni interaction has
      virtually disappeared.

PMID- 16896435
TI  - Tetraethyl stannane: structure, conformations, and orientational order when
      dissolved in a nematic liquid crystalline solvent.
AB  - Quantum chemical calculations are used to investigate the structure and the
      distribution of conformers of tetraethyl stannane, and these are compared with
      those of tetraethyl methane. The calculations predict that the most abundant
      conformers in tetraethyl stannane are those with symmetry C1, in contrast to
      tetraethyl methane, in which the D2d and S4 conformers are dominant. The
      structural and conformational information on tetraethyl stannane are then used,
      together with the additive potential model, to explain the finite quadrupolar
      splittings observed in the deuterium NMR spectrum of tetraethyl stannane
      dissolved in a nematic liquid crystalline solvent. This analysis emphasizes that
      to understand the orientational order of a flexible molecule in a liquid
      crystalline phase it is essential to consider the symmetry of individual
      conformers rather than that of an average structure.

PMID- 16896436
TI  - CO- and N2-FTIR characterisation of oxidised Rh species supported on
      Ce0.68Zr0.32O2.
AB  - The identification of a Rh-oxidised species of a Rh(0.29)/Ce0.68Zr0.32O2 catalyst
      that exhibits peculiar CO-O2 kinetics [I. Manuel, J. Chaubet, C. Thomas, H.
      Colas, N. Matthess and G. Djega-Mariadassou, J. Catal. 2004, 224, 269] is
      addressed. For this purpose, various catalysts are studied by XANES, CO- and N2
      FTIR, and benzene hydrogenation. The results obtained, particularly from N2-FTIR,
      which is, to our knowledge, reported for the first time on this kind of catalyst,
      suggest that Rh is mainly stabilised as electron-deficient clusters (Rhndelta+)
      on a Rh(0.29)/Ce0.68Zr0.32O2 catalyst after reduction at 500 degrees C under H2.
      The existence of these species, which may be caused by either electron
      perturbation induced on the metal by the reduced support or electron withdrawal
      from the metal clusters by an inductive effect of the neighbouring Cl anions, is
      also revealed through CO-FTIR experiments. In the presence of CO, however,
      evidence of RhI(CO)2 species is also provided.

PMID- 16896437
TI  - Comprehensive time-lag measurement as a diagnostic and analytical tool for non
      Fickian transport studies: a salient porous barrier-gaseous permeant test case.
AB  - Concentration-independent permeation of He, Ne and N2 through a porous barrier,
      specially constructed by multistep compaction of fine "Carbolac" carbon powder,
      has been studied. Emphasis was placed on measuring a variety of time lags,
      supplemented with transient permeation and sorption kinetics. Previous time-lag
      data, restricted to values of a single time-lag parameter, were instrumental in
      revealing deviations from Fick's law in similar solid barrier-penetrant systems;
      however, they could only provide indirect evidence as to the nature of the
      underlying causes, namely, time- or spatial dependence of the relevant transport
      parameters. Thus, an interpretation in terms of time-dependence (induced by the
      presence of blind pores) was proposed, predicated on calculations indicating
      that, in theory, spatial dependence (induced by non-uniform compaction) could be
      reduced to insignificance by adoption of a suitable multistep powder compaction
      technique. The comprehensive time-lag analysis approach applied here is a general
      diagnostic and analytical tool, previously successfully tested on graphite
      barriers, that can discriminate rigorously between the aforementioned non-Fickian
      functional dependences, as well as provide additional substantial information in
      either case. This capability is well illustrated by the results obtained in the
      system under study here, which provide unequivocal evidence of substantial
      spatial dependence. Furthermore, it is shown that the predicted functional form
      of the detected spatial dependence (i) can, in conjunction with an adequate
      physical model and with the results of a previous theoretical parametric study,
      account fully for all aspects of the observed non-Fickian time-lag behaviour and
      (ii) correlates satisfactorily with variation of local porosity across the
      barrier, detected by a suitable X-ray imaging technique. On the other hand, there
      is no evidence, from time lags or transient kinetics, of any significant time
      dependence attributable to slow filling or emptying of blind pores or to other
      causes.

PMID- 16896438
TI  - Kinetic studies of reactions of the nitrate radical (NO3) with peroxy radicals
      (RO2): an indirect source of OH at night?
AB  - A discharge-flow system, coupled to cavity-enhanced absorption spectroscopy
      (CEAS) detection systems for NO3 at lambda=662 nm and NO2 at lambda=404 nm, was
      used to investigate the kinetics of the reactions of NO3 with eight peroxy
      radicals at P approximately 5 Torr and T approximately 295 K. Values of the rate
      constants obtained were (k/10(-12) cm3 molecule-1 s-1): CH3O2 (1.1+/-0.5), C2H5O2
      (2.3+/-0.7), CH2FO2 (1.4+/-0.9), CH2ClO2 (3.8(+1.4)(-2.6)), c-C5H9O2 (1.2(+1.1)(
      0.5)), c-C6H11O2 (1.9+/-0.7), CF3O2 (0.62+/-0.17) and CF3CFO2CF3 (0.24+/-0.13).
      We explore possible relationships between k and the orbital energies of the
      reactants. We also provide a brief discussion of the potential impact of the
      reactions of NO3 with RO2 on the chemistry of the night-time atmosphere.

PMID- 16896439
TI  - Hyper-Rayleigh scattering as a means of monitoring crystal nucleation in
      solution.
AB  - Hyper-Rayleigh scattering is revealed as a very sensitive monitor of cluster
      formation in solution, and as a means of studying the mechanism of crystal
      nucleation in molecular species. Two compounds are selected with particularly
      high second harmonic generation (SHG) powers in the crystalline state and
      experimental conditions are defined allowing the measurement of the beta value
      for one of these as 18+/-1x10(-30) esu. It is found to agree with current
      theoretical prediction of 20x10(-30) esu. In the more powerful of these, two
      photon induced fluorescence is found to be partly responsible for the SHG. The
      solubilities of both compounds in methanol are measured and it is observed that
      these differ by a factor of ten. When the solution concentration is increased
      beyond 45% of the saturation value, the quadratic coefficient exhibits non-linear
      behaviour with respect to concentration. Additionally, the widths of the
      distributions of the HRS signals increase initially with concentration as
      expected, but, beyond 45% saturation concentrations, these narrow again. These
      phenomena are interpreted as indicators of cluster formation in these solutions
      well below saturation concentrations. A future experimental design is proposed in
      which the coherent component will yield information on the organisation of the
      molecules in such clusters.

PMID- 16896440
TI  - The heat of formation of gaseous PuO(2)2+ from relativistic density functional
      calculations.
AB  - Using a set of model reactions, we estimated the heat of formation of gaseous
      PuO2(2+) from quantum-chemical reaction enthalpies and experimental heats of
      formation of reference species. To this end, we carried out relativistic density
      functional calculations on the molecules PuO(2)2+, PuO2, PuF6, and PuF4. We used
      a revised variant (PBEN) of the Perdew-Burke-Ernzerhof gradient-corrected
      exchange-correlation functional, and we accounted for spin-orbit interaction in a
      self-consistent fashion. As open-shell Pu species with two or more unpaired 5f
      electrons are involved, spin-orbit interaction significantly affects the energies
      of the model reactions. Our theoretical estimate for the heat of formation
      DeltafH degree 0(PuO2(2+),g), 418+/-15 kcal mol-1, evaluated using plutonium
      fluorides as references, is in good agreement with a recent experimental result,
      413+/-16 kcal mol-1. The theoretical value connected to the experimental heat of
      formation of PuO2(g) has a notably higher uncertainty and therefore was not
      included in the final result.

PMID- 16896441
TI  - Assignment of dielectric loss of K-L zeolite.
AB  - Dielectric spectra of zeolite L (LTL) with potassium ions were measured to
      investigate movements of potassium ion in it. K,TMA-L was prepared through an ion
      exchange of K9-L with tetramethylammonium (TMA) ion, and changed to K,H-L by
      gentle calcination in air. Since the TMA ion in K,TMA-L was expected to
      exclusively occupy site D, the hydrogen ion in K,H-L was considered to be located
      around site D. K9-xHx-L with 0<or=x<or=1.1 showed an apparent single loss peak,
      and the magnitude of loss peak decreased with increasing x. Based on the
      variation of magnitude of loss peak with x, the loss was attributed to movements
      of K+/D. The apparent single peak contained two loss peaks. The reason why the
      movements of K+/D brought about two losses was due to jumps among three
      inequivalent sites containing the site D. The activation energy of movement
      related to the main loss decreased with an increase in x. The decrease in
      activation energy was explained by the influence of cation-cation repulsion,
      namely, the repulsion energy between K+/D and cation/neighbor-D decreases after
      the replacement of K+/neighbor-D with a hydrogen ion because of the increase in
      distance between cations, and hence the activation energy of movement of K+/D
      decreases.

PMID- 16896442
TI  - Sticking coefficient and pressure dependence of desorption rate in the
      statistical rate theory approach to the kinetics of gas adsorption. Carbon
      monoxide adsorption/desorption rates on the polycrystalline rhodium surface.
AB  - The statistical rate theory (SRT) fundamental kinetic equation for the Langmuir
      model of adsorption reveals some features which are difficult to understand.
      These are the infinitely high adsorption rate for zero coverage limit, infinitely
      high desorption rate at full saturation of the surface and dependence of the
      desorption rate on the adsorbate pressure. These features do not allow for a
      correct formulation of such important physical parameters as sticking and initial
      sticking probabilities. In this work these peculiar features of the fundamental
      SRT kinetic equation are discussed and explained. It is shown that the non
      physical behavior of the SRT kinetic equation follows from neglecting possible
      changes of adsorbate concentration near the adsorbing surface. A simple model
      accounting for the changes of adsorbate concentration close to the adsorbing
      surface is discussed. As a result, it was shown that application of even such a
      simple model leads to fully physical behavior of the SRT kinetic equation for the
      Langmuir model of adsorption. The model is used to build up equations describing
      the kinetics of adsorption/desorption of carbon monoxide on the energetically
      heterogeneous rhodium surface. The values of the parameters in these equations
      were determined from the analysis of equilibrium adsorption isotherms and from
      the description of experimental conditions. One additional parameter (having well
      defined limiting values) had to be adjusted in order to satisfactorily reproduce
      kinetic data. The experimental data used in this work were taken from the article
      by Yamada and Tamaru (T. Yamada and K. Tamaru, Surf. Sci., 1984, 138, L155).

PMID- 16896443
TI  - Metal ion selectivity of oligopeptides.
AB  - Metal binding affinity and selectivity of peptides are reviewed with a special
      emphasis on the high structural variety of peptide complexes. The most common
      structural type of these complexes is built up by the deprotonation and metal ion
      coordination of subsequent amide groups in the form of fused five-membered
      chelate rings. The metal ion selectivity of this process and the role of various
      anchoring groups are discussed in detail. The highest metal binding affinity of
      peptides is connected to the presence of two anchoring groups in appropriate
      location (the "double anchor"): e.g. the NH2-Xaa-Xaa-His/Cys/Asp/Met-Xaa
      sequence. Among the side chain donor functions, the imidazole of histidyl and
      thiolate of cysteinyl residues are the most effective ligating groups and their
      involvement in metal binding results in a great variety of different macrochelate
      or loop structures and/or formation of various polynuclear complexes. Examples of
      these structural motifs and their possible applications have been thoroughly
      discussed.

PMID- 16896444
TI  - A dinucleating ligand related to the beta-diketiminates.
AB  - A new ligand conceptually creates two sites reminiscent of beta-diketiminates,
      and upon deprotonation the salts exist in oligomeric forms with potassium ions
      linking multiple ligands.

PMID- 16896445
TI  - Enhanced hydrolytic activity of Cu(II) and Zn(II) complexes in highly cross
      linked polymers.
AB  - The chelate ligand tris[(1-vinylimidazol-2-yl)methyl]amine (5) was synthesized in
      five steps from commercially available starting materials. Upon reaction with
      ZnCl2 or CuCl2 in the presence of NH4PF6, the complexes [Zn5Cl]PF6 (6) and
      [Cu5Cl]PF6 (7) were obtained. The structure of both complexes was determined by
      single-crystal X-ray crystallography. Immobilization of 6 and 7 was achieved by
      co-polymerization with ethylene glycol dimethacrylate. The supported complexes P6
      Zn and P7-Cu were found to be efficient catalysts for the hydrolysis of bis(p
      nitrophenyl)phosphate (BNPP) at 50 degrees C. At pH 9.5, the heterogeneous
      catalyst P7-Cu was 56 times more active than the homogeneous catalyst 7.
      Partitioning effects, which increase the local concentration of BNPP in the
      polymer, are shown to contribute to the enhanced activity of the immobilized
      catalyst.

PMID- 16896446
TI  - The hydration of the scandium(III) ion in aqueous solution and crystalline
      hydrates studied by XAFS spectroscopy, large-angle X-ray scattering and
      crystallography.
AB  - The structures of the hydrated scandium(III) ion and of the hydrated dimeric
      hydrolysis complex, [Sc2(mu-OH)2]4+, in acidic aqueous solutions have been
      characterized by X-ray absorption fine structure (XAFS) and large-angle X-ray
      scattering (LAXS) methods. Comparisons with crystalline reference compounds
      containing hydrated scandium(III) ions in well characterized six-, seven- and
      eight-coordinated polyhedra have been used to evaluate the coordination numbers
      and configurations in aqueous solution. In strongly acidic aqueous solution the
      structure of the hydrated scandium(III) ion is found to be similar to that of the
      eight-coordinated scandium(III) ion with distorted bicapped trigonal prismatic
      coordinating geometry in the crystalline [Sc(H2O)(8.0)](CF3SO3)3 compound. The
      EXAFS data reveal for the solution, as for the solid, a mean Sc-O bond distance
      of 2.17(1) Angstrom to six strongly bound prism water molecules, 2.32(4) Angstrom
      to one capping position, with possibly another capping position at about 2.5
      Angstrom. The LAXS study supports this structural model and shows furthermore a
      second hydration sphere with approximately 12 water molecules at a mean
      Sc...O(II) distance of 4.27(3) Angstrom. In less acidic concentrated
      scandium(III) aqueous solutions, the dimeric hydrolysis product, [Sc2(mu
      OH)2(H2O)10]4+, is the predominating species with seven-coordinated scandium(III)
      ions in a double hydroxo bridge and five terminal water molecules at a mean Sc-O
      bond distance of 2.145 Angstrom. Hexahydrated scandium(III) ions are found in the
      crystal structure of the double salt [Sc(H2O)6][Sc(CH3SO3)6], which crystallizes
      in the trigonal space group R3[combining macron] with Z = 6 and the unit cell
      dimensions a = 14.019(2) and c = 25.3805(5) Angstrom. The Sc-O distances in the
      two crystallographically unique, but nearly identical, [Sc(H2O)6]3+ entities
      (both with 3[combining macron] imposed crystallographic symmetry) are 2.085(6)
      and 2.086(5) Angstrom, while the mean Sc-O distance in the near octahedral
      [Sc(OSO2CH3)6]3- entities (with three-fold symmetry) is 2.078 Angstrom.

PMID- 16896447
TI  - The homologous series of 1,1'-ferrocenylenebisdihalophosphanes (C5H4PX2)2Fe (X =
      F, Cl, Br, I): precursors for the first metallocene bridged bisphosphaalkene.
AB  - A facile synthetic access to the homologous series of 1,1'-ferrocenylene
      bisdihalophosphanes Fc'(PX2)2 (X = F, Cl, Br, I; Fc' = 1,1'-ferrocenediyl =
      ferrocenylene = -C5H4FeC5H4-) is reported. The 31P NMR spectroscopic data of this
      series suggest a similar electronic interaction of the -PX(2) unit with the
      ferrocene system as in monofunctional ferrocenyldihalophosphanes. Crystal
      structures for Fc'(PCl2)2 and Fc'(PBr2)2 reveal that the nature of the halogen
      atom within the phosphane unit strongly influences the twist angle of the
      ferrocene system, while leaving the other structural parameters mostly
      unaffected. Based on these bisdihalophosphanes, a synthetic access to the first
      metallocene bridged bisphosphaalkene ((C5H4P=C(t-Bu)OTMS)2Fe) is reported in
      which the tert-butyl substituents provide sufficient steric pressure to control
      the E/Z isomeric ratio which leads to the almost exclusive formation of the most
      stable Z,Z isomer out of the three possible isomers.

PMID- 16896448
TI  - Ring-opening polymerization of coordination complexes: silver(I) complexes with
      bis(amidopyridine) ligands derived from thiophene.
AB  - The thiophene-based bis(N-methylamido-pyridine) ligand SC4H2-2,5-{C(=O)N(Me)-4
      C5H4N}2 reacts with silver(I) salts AgX to give 1 : 1 complexes, which are
      characterized in the solid state as the macrocyclic complexes [Ag(2){SC4H2-2,5
      (CONMe-4-C5H4N)2}2][X]2, which have the cis conformation of the C(=O)N(Me) group,
      when X = CF3CO2, NO3, or CF3SO3 but as the polymeric complex [Ag(n){SC4H2-2,5
      (CONMe-4-C5H4N)2}n][X]n, with the unusual trans conformation of the C(=O)N(Me)
      group, when X = PF6. The bis(amido-pyridine) ligand SC4H2-2,5-{C(=O)NHCH2-3
      C5H4N}2 reacts with silver(I) trifluoroacetate to give the polymeric complex
      [Ag(n){SC4H2-2,5-(CONHCH2-3-C5H4N)2}n][X]n, X = CF3CO2. The macrocyclic complexes
      contain transannular argentophilic secondary bonds. The polymers self assemble
      into sheet structures through interchain C=O...Ag and S...Ag bonds in
      [Ag(n){SC4H2-2,5-(CONMe-4-C5H4N)2}n][PF6]n and through Ag...Ag, C=O...Ag and
      Ag...O(trifluoroacetate)...HN secondary bonds in [Ag(n){SC4H2-2,5-(CONHCH2-3
      C5H4N)2}n][CF3CO2]n.

PMID- 16896450
TI  - Dynamic equilibrium between cyclic oligomers. Thermodynamic and structural
      characterization of a square and a triangle.
AB  - A dynamic equilibrium has been found in CDCl3 between a neutral molecular square,
      [cis-Mo2(DAniF)2]4(O2CC6F4CO2)4 (1) and triangle, [cis-Mo2(DAniF)2]3(O2CC6F4CO2)3
      (2) (DAniF = the anion of N,N'-di-p-anisylformamidine). The two components have
      been crystallographically characterized and solution studies by 1H and 19F NMR
      spectra of the concentration- and the temperature-dependence of the equilibrium
      have been performed. The conversion of three moles of molecular squares 1 to four
      moles of molecular triangles 2 has an equilibrium constant of 1.98(7) x 10(-4) at
      23.7 degrees C. At this temperature, the DeltaG(0) for the conversion of three
      moles of squares to four moles of triangles is 21.0 kJ mol(-1). The conversion is
      enthalpically disfavored (DeltaH(0) = 23.5 kJ mol(-1)), but entropically favored
      (DeltaS(0) = 8.2 J K(-1) mol(-1)).

PMID- 16896449
TI  - Multiple metal binding to 6-oxopurine nucleobases as a source of deprotonation.
      The role of metal ions at N7 and N3.
AB  - Simultaneous metal coordination to N7 (Pt(II)) and N3 (Pd(II)) of N9-blocked
      guanine leads to a 10(4) fold acidification of the guanine-N(1)H position and
      hence to a virtual complete deprotonation of the N(1)H position at neutral pH.
      The chelate-tethered nucleobase ethylenediamine-N9-ethylguanine was employed and
      relevant acid-base equilibria were studied by pD dependent 1H NMR spectroscopy.
      CH2 resonances of the tether were assigned on the basis of NOESY and COSY
      experiments. Our findings suggest a plausible method of formation of a previously
      reported trinuclear Pt(II) complex of 9-ethylguanine with metals coordinated to
      N1, N3 and N7. According to this, a sequence with the first metal binding to N7,
      the second one binding to N3, and only the third one binding to N1 with
      deprotonation of this site is proposed.

PMID- 16896451
TI  - Structure and magnetic properties of carbonate-bridged five-coordinate nickel(II)
      complexes controlled by solvent effect.
AB  - CO2 and HCO3- react with the dinuclear hydroxo-complex [Ni(mcN3)(mu-OH)]2(PF6)2
      (mcN3 = 2,4,4,9-tetramethyl-1,5,9-triazacyclododec-1-ene) to form micro-CO3
      bridged nickel(II) complexes, [{Ni(mcN3)}2(mu-CO3)](PF6)2 (1a) with a symmetric
      core in which both nickel atoms are five-coordinate and [Ni(mcN3)(mu
      CO3)Ni(mcN3)(MeCN)](PF6)2 (1b) with an asymmetric dinuclear core containing five-
      and six-coordinate nickel atoms. The magnetic behaviour indicates the existence
      of antiferromagnetic coupling between the metallic centres. A substantial
      increase in the value of J occurs when the symmetric five-coordinate nickel
      species transforms to an asymmetric five- and six-coordinate species by axial
      coordination of acetonitrile.

PMID- 16896452
TI  - Formation of a layered framework structure based upon 4-methyl-2,6
      bis(methylphosphonic acid) phenol.
AB  - The trifunctional ligands, [(HO)2P(O)CH2]2C6H2(R)OH, (5-H4)(R = CH3, Br) were
      prepared in good yield via an Arbusov reaction between P(OEt)3 and the respective
      4-R-2,6-bis(chloromethyl)phenols followed by acidic aqueous hydrolysis and they
      were spectroscopically characterized by IR and NMR techniques. The ligand 5-H4
      CH3 readily dissolves lanthanide hydroxide residues and it forms a crystalline
      complex from aqueous LaCl3 solutions. This complex was characterized by single
      crystal X-ray diffraction methods and found to adopt a complex 2-D lamellar
      network in the bc plane. The La(III) inner coordination sphere is seven
      coordinate formed by oxygen atoms from two water molecules and five phosphonate
      oxygen atoms from three different ligands. The phenolic oxygen atom is not
      involved in the ligand binding to La(III).

PMID- 16896453
TI  - Mesomorphism of ionic allylpalladium(II) complexes containing pz(R2)py as ligands
      and [BF4]-, [PF6]- or [CF3SO3]- as counteranions.
AB  - The synthesis and thermal behaviour is reported of some ionic liquid-crystalline
      complexes formed when a mesogenic, two-chained, pyrazolylpyridine ligand is bound
      to a eta3-allylpalladium(II) fragment. The phase behaviour of the complexes is
      dominated by the formation of the SmA phase and, while the stability of the
      crystal phase appears to be controlled by intermolecular solid-state
      interactions, the stability of the liquid crystal phases is controlled by the
      length of the ligand alkoxy chains. Some of the complexes also show a complex
      polymorphism leading to the observation of double-melting behaviour.

PMID- 16896454
TI  - Rhodium(I) and iridium(I) complexes of pyrazolyl-N-heterocyclic carbene ligands.
AB  - Several Rh(I) and Ir(I) complexes containing an N-heterocyclic carbene-pyrazolyl
      chelate ligand have been synthesised. Determination of the single-crystal X-ray
      structure of the Ir(I) complex showed a novel binding mode with the iridium
      centre coordinated to two ligands via two carbene donors in preference to one
      ligand forming the entropically favoured chelate. The hydrogenation activity of
      several of these complexes was investigated along with that of previously
      synthesised Rh(I) and Ir(I) complexes containing an analogous phosphine-pyrazolyl
      chelate.

PMID- 16896455
TI  - Regioselectivity in aqueous palladium catalysed hydroxycarbonylation of styrene:
      a catalytic and mechanistic study.
AB  - Regioselectivity control was studied in palladium catalysed hydroxycarbonylation
      of styrene in neat water with water-soluble phosphines, mostly trisulfonated
      triphenylphosphine, TPPTS, but also N-bis(N',N'-diethyl-2-aminoethyl)-4
      aminomethylphenyl-diphenylphosphine, N3P. The factor giving the highest changes
      in regioselectivity in the TPPTS system, under similar reaction conditions, is
      the temperature. In the N3P case, only a minor variation in the n/i ratio as a
      function of temperature is observed. Insitu normal- and high-pressure NMR
      experiments were performed to obtain further information about the catalytic
      cycle and the reaction intermediates. Two palladium hydride intermediates, a
      palladium eta3-benzylic complex and both the branched and linear palladium acyl
      complexes were identified in the HP NMR experiments. The hydroxycarbonylation in
      water using styrene as a substrate operates using a hydride mechanism for
      pathways leading to both linear and branched product. Insertion of styrene in the
      palladium-hydride bond gives an eta3-benzyl compound. A high CO pressure gives a
      kinetic preference for the iso-acyl in the next step. In the TPPTS system, at
      moderate temperatures, the hydrolysis of the iso-acyl is faster than its
      conversion to the thermodynamically more stable n-acyl. A low n/i therefore
      requires high pressures and reasonably low temperatures. The N3P ligand always
      favours the linear product since isomerisation of the iso-acyl to the n-acyl in
      this system is fast under all conditions investigated.

PMID- 16896456
TI  - Synthesis, spectroscopic and structural characterization of tertiary phosphine
      tellurium dihalides Et3PTeX2(X = Cl, Br, I).
AB  - The reactions of triethylphosphine telluride with SO2Cl2 or I2 produced the first
      structurally characterized tellurium-containing tertiary phosphine chalcogen
      dihalides, Et3PTeCl2 and Et3PTeI2, respectively, in good yields. The
      corresponding dibromide, Et3PTeBr2, was obtained by an in situ reaction between
      Et3PTeCl2 and two equivalents of Me3SiBr. This series of compounds has been
      characterized in the solid state by X-ray structural analyses and in solution by
      multinuclear NMR spectra. The structures of Et3PTeX2(X = Cl, Br, I) all show a T
      shaped geometry around tellurium with weak Te...halogen interactions giving rise
      to centrosymmetric dimers. NMR data indicate that Et3PTeI2 exhibits the weakest P
      Te bond in solution. The ionic complexes, [(Et3PO)2H]2[Te2I6] and
      [(Et3PO)2H]2[TeI4], were isolated from THF solutions of Et3PTeI2 and
      characterized by X-ray structural determinations.

PMID- 16896459
TI  - Wildlife biomaterial banking in Africa for now and the future.
AB  - The Wildlife Biological Resource Centre (wBRC) together with its partners in
      BioBank SA, have created a Biological Resource Bank (BRB) that is dedicated to
      the acquisition, processing, banking, using and provision of biomaterials to the
      scientific and conservation industry that are viable, diverse and representative
      of southern Africa's wildlife populations. Banked biomaterials include tissue
      such as muscle, kidney, fat, liver, embryos, fibroblast cultures, blood, sperm,
      hair, egg shells and other tissue, fluids and cells. Biomaterials are made
      available for research, biodiversity conservation and biotechnology development.
      Biomaterials are used in many disciplines, including genetics, reproduction,
      nutrition, and disease studies. Biomaterials from selected species are also
      useful for the detection and monitoring of Persistent Organic Pollutants and
      other potentially harmful substances found in the environment. Biomaterials are
      made available to third parties with prior consent from the biomaterials "owner"
      and only after the signing of a customised Material Transfer Agreement (MTA) or
      Cooperative Research and Development Agreement (CRADA). The training of staff
      from National and Provincial Game Reserves, Zoological Gardens, Animal Breeders
      and laboratories is carried out on a regular basis with the aim of securing good
      quality biomaterials. Sampling kits are made available to persons tasked with the
      collection of wildlife biomaterials. The Biobank SA consortium acts as an
      integrated resource centre linking partner collections. The consortium's
      operational arm, namely wBRC, is active in the development of relevant policy,
      regulations and legislation pertaining to biomaterials, including Access and
      Benefit Sharing systems. The main sponsor of the project is the Department of
      Science and Technology, National Government of South Africa.

PMID- 16896460
TI  - Environmental Specimen Bank in Ehime University (es-BANK), Japan for global
      monitoring.
AB  - During the last 40 years, The Center for Marine Environmental Studies (CMES),
      Ehime University collected a variety of environmental and biological material
      comprising about 1000 species and 100,000 samples from many developing and
      developed countries and also open seas and oceans all over the world. They were
      categorically archived, catalogued and stocked in our Environment Specimen Bank
      (es-BANK) facility equipped with a -25 degrees C cold room. We have already
      exchanged specimens with many scientific institutions and are also eager to widen
      our collaboration with other specimen banks. In our survey using the air, water,
      wildlife and human samples, we found that the major emission sources for the
      industrial chemicals like polychlorinated biphenyls (PCBs) are in the developed
      nations while those of organochlorine (OC) pesticides like
      dichlorodiphenyltrichloroethane and its metabolites (DDTs), hexachlorocyclohexane
      isomers (HCHs), etc. are located in developing countries. However, significant
      emission of modern environmental contaminants such as polybrominated diphenyl
      ethers (PBDEs) also seems to occur predominantly in countries with high economic
      growth rates. Apart from the modern incinerators and other industrial
      installations in developed nations, the compounds, like dioxins and related
      compounds (DRCs), were also found to be released in significant levels from the
      municipal solid waste dumping sites of developing countries. By evaluating the
      distribution patterns of various persistent toxic substances (PTSs) in our
      studies, we could conclude that DRCs and DDTs are regional contaminants, while
      PCBs, PBDEs, HCHs and hexachlorobenzene (HCB) are global contaminants. We also
      found that the pollution by PBDEs has been increasing in the last two decades
      while that of the legacy OCs has been decreasing.

PMID- 16896461
TI  - The environmental specimen bank, Swedish Museum of Natural History-a base for
      contaminant monitoring and environmental research.

PMID- 16896462
TI  - The U.S. National biomonitoring specimen bank and the marine environmental
      specimen bank.
AB  - The National Biomonitoring Specimen Bank (NBSB), established in 1979 at the NIST
      Neutron Research Facility, Gaithersburg, Maryland, was specifically designed to
      store environmental specimens over long periods of time (50-100 years). This bank
      contains specimens (e.g., human livers, marine sediments, fish tissues, mussels,
      oysters, human diet samples, and marine mammal tissues) collected as part of
      several monitoring and research programs supported by U.S. Federal agencies. In
      2002, NIST completed the construction of a second environmental specimen bank
      facility specifically designed for supporting monitoring and research on marine
      environmental health issues. This facility, the Marine Environmental Specimen
      Bank (Marine ESB) is located at the Hollings Marine Laboratory in Charleston,
      South Carolina, in partnership with a U.S. Federal resource agency, two
      universities, and a State of South Carolina resource agency. The Marine ESB
      provides a resource of research specimens that are used to address questions
      regarding temporal and geographic trends in environmental contamination, genetic
      separation of populations of animals, and the health status of various types of
      marine animals. Specimens banked include marine mammal tissues, bird tissues,
      mussels, and oysters. Plans are underway to establish protocols and initiate
      banking procedures for other types of marine organisms and environmental
      materials as part of an expanded effort to support research on the health of
      marine biota.

PMID- 16896463
TI  - The US National Cancer Institute's natural products repository; origins and
      utility.
AB  - The US National Cancer Institute's natural products collection program has been
      running since 1986 and over the years the materials collected and processed have
      been stored in a repository that as a result of initial planning, has permitted
      the establishment of a national resource that is now being utilized as a drug
      discovery tool for any disease of interest to the NIH by researchers world-wide.
      This paper describes the history of the program.

PMID- 16896464
TI  - Polycyclic aromatic hydrocarbons in pine and spruce shoots-temporal trends and
      spatial distribution.
AB  - In the framework of the German environmental specimen bank one-year old spruce
      shoots (Picea abies) and pine shoots (Pinus sylvestris) serve as bioindicators
      for the atmospheric pollution. Sampling is performed in two urbanized areas in
      western and eastern Germany (Warndt and Duebener Heide, respectively), and in
      seven different rural locations. Prior to archiving conifer shoots are
      continuously analyzed for a set of 17 individual polycyclic aromatic hydrocarbons
      (PAHs). The results from the two urbanized areas show that the atmospheric
      contamination with PAH has declined by about 75% between 1985 and 2004 at Warndt
      and by about 85% between 1991 and 2004 at Duebener Heide. However, summation
      operatorPAH concentrations stayed virtually constant at both locations since the
      end of the 1990s at levels of about 100 ng g(-1) wet weight (ww). In spruce
      shoots from rural areas current concentrations of PAHs are significantly lower
      and vary between 8 and 61 ng g(-1) ww. In all shoot samples the four low
      molecular aromatics phenanthrene, fluoranthene, pyrene, and chrysene dominate the
      pattern by contributing 60 to 90% to summation operatorPAH. The group of high
      molecular weight aromatics is dominated by benzo[b,j,k]fluoranthene, especially
      in spruce shoots originating from greater altitudes remarkable amounts of six and
      seven ringed PAHs could be detected. Despite the strong decrease of PAH
      concentrations in urban areas patterns of aromatics remained nearly unchanged in
      the observation period 1985 to 2004.

PMID- 16896465
TI  - Retrospective monitoring of synthetic musk compounds in aquatic biota from German
      rivers and coastal areas.
AB  - The polycyclic musk compounds HHCB (Galaxolide) and AHTN (Tonalide) are commonly
      used as synthetic fragrances in personal care products and household cleaners.
      These and other synthetic musk fragrances were quantified in different aquatic
      samples from the German Environmental Specimen Bank (ESB). While HHCB and AHTN
      were found in almost all samples, most of the other musk fragrances were detected
      only in a few samples and mostly at lower concentration levels. Blue mussels from
      the North Sea showed varying levels of 0.5-1.7 ng g(-1) ww for HHCB and 0.4-2.5
      ng g(-1) ww for AHTN (ww, wet weight) in the period from 1986 to 2000, while blue
      mussels from the Baltic Sea were only slightly contaminated with synthetic musk
      fragrances. Lipid weight-related concentrations of synthetic musk compounds in
      blue mussels were higher than in eelpout muscles, bladder wrack and herring gull
      eggs. In comparison to the marine specimens, muscles of bream from German rivers
      had higher concentrations of HHCB and AHTN. The ranges of HHCB and AHTN
      concentrations in bream from the Elbe River were 545-6400 ng g(-1) lw and 48-2130
      ng g(-1) lw, respectively (lw, lipid weight; five sampling sites, period 1993
      2003). In the Rhine River, HHCB and AHTN levels of bream muscles were highest at
      the Iffezheim site (up to 9750 ng g(-1) lw HHCB, 1998). Even higher synthetic
      musk levels were detected in bream from the rivers Saale and Saar. In recent
      years, levels of both compounds determined in bream from most sampling sites have
      decreased from maximum values in the 1990s. As the concentrations of AHTN have
      decreased faster, the ratio of HHCB to AHTN increased from 2-4 in the 1990s to 10
      20 in recent years.

PMID- 16896466
TI  - Decreasing lead levels in Swedish biota revealed by 36 years (1969-2004) of
      environmental monitoring.
AB  - Since the 1980s, lead levels decreased significantly in most marine biota from
      the Baltic Sea, the Kattegatt and the Skagerrack and in terrestrial biota from
      south and central Sweden, analysed in the National Swedish Environmental
      Monitoring Programme. In herring and cod liver, the decrease was 4.2-7.1%
      annually 1981-2003 and in perch liver and guillemot eggs analysed since the
      middle of the 1990s the decrease was 10-13%. In kidneys of young starlings from
      south and central Sweden, lead levels decreased 6.2-12% annually and the annual
      decrease in liver and kidney from young moose was 8.8% and 6.5%, respectively. In
      northern Sweden, lead levels decreased in pike liver by 2.8% between 1969 and
      1994 and in reindeer liver by 3.5% annually while a significant increase (5%
      annually 1981-1994) has been detected in arctic char. In some marine biota, there
      were indications of a larger decrease during the last ten years compared to the
      whole period. The large decline in lead emission to the atmosphere during the
      last twenty years, mainly because of decreasing use of leaded gasoline has
      obviously resulted in decreasing lead levels in biota.

PMID- 16896467
TI  - Comprehensive re-analysis of archived herring gull eggs reconstructs historical
      temporal trends in chlorinated hydrocarbon contamination in Lake Ontario and
      Green Bay, Lake Michigan, 1971-1982.
AB  - Herring gull egg homogenates collected between 1971 and 1982 from a colony in
      central Lake Ontario (Scotch Bonnet Island) and from a colony in central Green
      Bay, Lake Michigan (Big Sister Island) were archived in the Canadian Wildlife
      Service Specimen Bank. Pooled samples (N = 10) were exhaustively analyzed in 1993
      for a wide range of individual chlorinated hydrocarbon contaminant (CHC)
      compounds: DDT, mirex and chlordane compounds and metabolites, chlorobenzenes
      (CBzs), dieldrin, chlorostyrenes (CSs), hexachlorocyclohexanes (HCHs),
      polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs), and 87 PCB
      congeners, including the TCDD-like non-ortho and mono-ortho congeners. PCBs and
      DDTs were the dominant residues in eggs from both Lake Ontario (31-242 mg kg(-1)
      and 9-64 mg kg(-1)) and Green Bay (34-133 mg kg(-1) and 14-91 mg kg(-1)).
      SigmaPCBs declined by a factor of 4-5 and DDTs a factor of 4-7 at both colonies
      between 1971 and 1982. Lake Ontario eggs had significantly higher residues of
      2,3,7,8-TCDD (0.2-2.0 microg kg(-1)), HCBz (0.1-4.7 mg kg(-1)), OCS (0.03-0.45 mg
      kg(-1)), three HpCSs (0.13-0.97 mg kg(-1)), mirex and mirex photodegradation
      products (2.1-9.2 mg kg(-1)) than Green Bay eggs. HCBz levels in Lake Ontario
      eggs declined a factor of 40, TCDD and chlorostyrenes a factor of 8-10, and mirex
      a factor of 4 between 1971-1978. Green Bay eggs had slightly higher levels of
      chlordane-related compounds, dieldrin and beta-HCH than Lake Ontario eggs. There
      were no consistent or strong trends in residue levels of these pesticides, PCDDs
      (except TCDD) and PCDFs in either lake, indicating that rates of input and
      removal of these CHCs in the lakes were much closer in the early 1970s than was
      the case for the other compounds.

PMID- 16896469
TI  - Peptides of aminoxy acids as foldamers.
AB  - This Feature Article summarizes our efforts in developing a new family of
      foldamers from alpha-, beta- and gamma-aminoxy acids. From a series of
      conformational studies, we demonstrate that peptides consisting of aminoxy acids
      adopt several well-defined secondary structures, such as alpha N-O turns (which
      feature an eight-membered-ring hydrogen bond), beta N-O turns (a nine-membered
      ring hydrogen bond), gamma N-O turns (a ten-membered-ring hydrogen bond), 1.8(8)
      helices (consecutive homochiral alpha N-O turns), 7/8 helices (alternating alpha
      N-O turns and gamma-turns), 1.7(9) helices (consecutive beta N-O turns), reverse
      turns (consecutive heterochiral alpha N-O turns) and sheet-like structures.

PMID- 16896468
TI  - Persistent organic pollutants in Alaskan ringed seal (Phoca hispida) and walrus
      (Odobenus rosmarus) blubber.
AB  - Since 1987, the Alaska Marine Mammal Tissue Archival Project (AMMTAP) has
      collected tissues from 18 marine mammal species. Specimens are archived in the
      National Institute of Standards and Technology's National Biomonitoring Specimen
      Bank (NIST-NBSB). AMMTAP has collected blubber, liver and/or kidney specimens
      from a number of ringed seals (Phoca hispida) from the areas near Nome and
      Barrow, Alaska and walruses (Odobenus rosmarus) from several locations in the
      Bering Sea. Thirty-three ringed seal and 15 walrus blubber samples from the NIST
      NBSB were analyzed for persistent organic pollutants (POPs). The compounds
      determined included PCBs (28 congeners or congener groups), DDT and related
      compounds, hexachlorobenzene (HCB), hexachlorocyclohexane isomers (HCHs),
      chlordanes, dieldrin, and mirex. POP concentrations in ringed seal blubber were
      significantly higher in Barrow than in Nome when statistically accounting for the
      interaction of age and gender; HCB, however, was not statistically different
      between the two locations. Unlike males, POP concentrations and age were not
      significantly correlated in females probably as a result of lactational loss. POP
      concentrations in walrus blubber were lower than in ringed seal blubber for
      SigmaPCBs, chlordanes, and HCHs, but higher for dieldrin and mirex. POP
      concentrations in ringed seals and walrus from Alaska provide further evidence
      that the western Arctic tends to have lower or similar POP concentrations
      compared to the eastern Canadian Arctic.

PMID- 16896470
TI  - Enantioselective synthesis on the solid phase.
AB  - Organic transformations on substrates which are immobilized on an insoluble,
      polymeric carrier have found broad application in compound collection synthesis.
      In contrast to other synthetic methodologies in solid-phase organic synthesis,
      reactions that afford non-racemic products are strikingly under-represented. Not
      only does the introduction of stereoinformation on immobilized, achiral starting
      materials provide enantioenriched products which can be of value for biological
      testing, but it also opens up new perspectives for accessible structures. This
      feature article gives an overview of successful enantioselective transformations
      on a solid support. Critical differences in the corresponding solution-phase
      protocols are highlighted, and applications to the generation of compound
      collections are particularly mentioned.

PMID- 16896471
TI  - On-bead screening of a library to detect host-guest complexation by an aniline
      reporter.
AB  - We developed a new labeling reagent and a color assay system in water to detect
      binding between target molecules and library members on beads, which is free of
      label-induced artifacts that can cause misleading results.

PMID- 16896472
TI  - Highly luminescent network films from electrochemical deposition of peripheral
      carbazole functionalized fluorene oligomer and their applications for light
      emitting diodes.
AB  - Highly luminescent network films on flat indium tin oxide (ITO) substrates are
      prepared by electropolymerization using an electroactive and fluorescent compound
      as precursor; the LEDs prepared using these films as a light emitting layer
      achieve the maximum luminance and external quantum efficiency of 4224 cd/m(2) and
      0.72%, respectively, which demonstrates that electrochemical synthesis can be a
      new route to construct the highly luminescent films.

PMID- 16896473
TI  - Reactions inside a porous nanocapsule/artificial cell: encapsulates' structuring
      directed by internal surface deprotonations.
AB  - In the cavities of unprecedentedly functionalised, spherical, porous capsules of
      the type {Pentagon}12{Linker}30 identical with
      [{(Mo)Mo5O21(H2O)6}12{Mo2O4(ligand)}30]n- reactions with the ligands -i.e. at the
      internal shell surfaces - can be performed, in the present case deliberate
      aquation/hydration and deprotonation reactions at the linker fragments
      {(Mo2O4)C2O4H}+ similar to that reported in the literature for [(NH3)5CoC2O4H]2+
      in solution.

PMID- 16896474
TI  - Columnar liquid crystalline pi-conjugated oligothiophenes.
AB  - Polycatenar oligothiophenes possessing three alkoxy chains at each terminal self
      organise into columnar liquid crystalline phases, and one-dimensional columnar
      stacks can be oriented uniaxially by mechanical shearing in the mesophases.

PMID- 16896475
TI  - Cryovoltammetrically probing functional group reductive cleavage: alkyl-sulfur
      versus aryl-sulfur bond cleavage in an alkyl naphthyl thioether under single
      electron-transfer is temperature switchable.
AB  - A series of single electron-transfer (SET) reactions on a naphthyl thioether have
      shown that the reductive cleavage mechanism changes at low temperatures and this
      selectivity is proved using an electrochemical analysis that mimics the SET
      reaction conditions.

PMID- 16896476
TI  - A new homogeneous zinc complex with increased reactivity for the intramolecular
      hydroamination of alkenes.
AB  - The new zinc compound N-cyclohexyl-2-(cyclohexylamino)troponiminate zinc methyl,
      [(Cy)2ATI]ZnMe, was synthesized and showed a superior reactivity in the
      intramolecular hydroamination reaction of non-activated alkenes compared to
      previously reported homogeneous zinc complexes.

PMID- 16896477
TI  - Phosphine-olefin ligands: a facile dehydrogenative route to catalytically active
      rhodium complexes.
AB  - Facile, metal-mediated, (acceptorless) dehydrogenation of tricyclopentyl
      phosphine directly affords rhodium chelating phosphine-olefin complexes, some of
      which are catalytically active for 1,4-additions.

PMID- 16896479
TI  - The synthesis of mesoporous silicates containing bimetallic nanoparticles and
      magnetic properties of PtCo nanoparticles in silica.
AB  - Using a one-pot approach employing true liquid crystal templating on neutral
      surfactants and simple metal salt precursors, mesostructured, mesoporous
      silicates have been prepared in which bimetallic nanoparticles are deposited;
      magnetic properties of PtCo systems so prepared are evaluated.

PMID- 16896480
TI  - Nanocrystalline cobalt oxide: a catalyst for selective alkane oxidation under
      ambient conditions.
AB  - Nanocrystalline cobalt oxide activates propane, yielding propene at room
      temperature and pressure.

PMID- 16896481
TI  - Unexpected epimerization at C2 in the Horner-Wadsworth-Emmons reaction of chiral
      2-substituted-4-oxopiperidines.
AB  - The observed epimerization at C2 in the Horner-Wadsworth-Emmons (HWE) reaction of
      chiral 2-substituted-4-oxopiperidines has been investigated and, on the basis of
      the experimental results, a mechanism for this unexpected process has been
      proposed.

PMID- 16896478
TI  - The preparation by true liquid crystal templating of mesoporous silicates
      containing nanoparticulate metals.
AB  - Mesostructured silicates containing metal nanoparticles have been synthesised via
      templating around a pre-formed, metal-containing mesophase using a non-ionic
      surfactant.

PMID- 16896482
TI  - Carbonyl-metal fragment insertion into eight-vertex [closo-1-CB7H8]-. Facile
      synthesis of ten-vertex metalladicarbollide complexes [2,2,2-(CO)3-1-OH-closo
      2,1,10-MC2B7H8]n-{M = Fe, Ru (n= 0), Mn, Re (n= 1)}.
AB  - Insertion of {M(CO)4} fragments (M = Fe, Ru, Mn, Re) into the eight-vertex
      monocarborane anion [closo-1-CB7H8]- affords ten-vertex metal-dicarbollide
      complexes.

PMID- 16896483
TI  - A new 17O-isotopic enrichment method for the NMR characterisation of phosphate
      compounds.
AB  - Heating phosphate compounds under (17)O-enriched water vapour is an easy and
      rapid method to prepare homogeneously enriched and pure samples for the
      acquisition of (17)O NMR spectra with a good sensitivity.

PMID- 16896484
TI  - On a novel coordination mode of phosphinine C5H5P.
AB  - In an unprecedented coordination mode two phosphinines simultaneously bridge a Mn
      Mn bond and the latter with two Mn(CO)3 fragments; the distortion of the
      resulting central heterobicyclo[1.1.0]butane unit follows from the Mn(18VE)
      requirement.

PMID- 16896485
TI  - Aptamer conformational switch as sensitive electrochemical biosensor for
      potassium ion recognition.
AB  - We report the first use of an electrochemical aptasensor for selective potassium
      recognition, based on a conformational change, affording an electric signal
      transduced electrochemically by square wave voltammetry or electrochemical
      impedance spectroscopy.

PMID- 16896486
TI  - Controlled synthesis of highly dispersed platinum nanoparticles in ordered
      mesoporous carbons.
AB  - A novel route has been developed to fabricate ordered carbon mesoporous materials
      with well-dispersed, highly stable Pt nanoparticles of ca. 2-3 nm on the pore
      walls using platinum acetylacetonate as the co-feeding carbon and Pt precursor.

PMID- 16896487
TI  - In situ generation of gold nanoparticles on a protein surface: Fischer carbene
      complex as reducing agent.
AB  - Suitably designed, hydrophilic Fischer carbene complexes reduce HAuCl4 to produce
      stable gold nanoparticles localized on proteins in aqueous buffer solution.

PMID- 16896489
TI  - Stereoselective synthesis of highly O-functionalized enantiopure 2,3,4
      trisubstituted tetrahydrofurans by tandem debenzylative cyclization of glycal
      derived 2,3-epoxy alcohols.
AB  - A new and highly efficient methodology for the construction of synthetically
      important highly O-functionalized enantiopure 2,3,4-trisubstituted
      tetrahydrofurans with three contiguous stereocenters is reported.

PMID- 16896488
TI  - Unprecedented formation of an acetamidate-bridged dinuclear platinum(II)
      terpyridyl complex-correlation of luminescence properties with the crystal forms
      and dimerization studies in solution.
AB  - An [corrected] acetamidate-bridged dinuclear platinum(ii) terpyridyl complex has
      been isolated in two crystal forms, a red form and a dark form, with different
      luminescence properties; electronic absorption, emission and (1)H NMR studies
      revealed the presence of a dimerization process in the solution state.

PMID- 16896490
TI  - Metal complex catalysis on a double stranded DNA template.
AB  - The reaction of ester hydrolysis catalysed by a DNA duplex in a sequence specific
      fashion has been developed, which is the fastest and most high yielding in
      comparison with the known reactions of this type.

PMID- 16896491
TI  - [Amebic granulomatosis encephalitis due to Balamuthia mandrillaris: fatal disease
      increasingly recognized in Latin America].

PMID- 16896492
TI  - [Infections caused by free-living amebas. Historical commentaries, taxonomy and
      nomenclature, protozoology and clinicopathologic features].
AB  - Infections caused by free-living amebae constitute one of emergent opportunistic
      infections with greatest medical interest. Although infrequently, they have been
      described in almost all world, its diagnosis depends on a high index of
      suspicion, especially in morpho-pathologic and laboratory studies. Exciting
      historical features of infections due to free-living amebae, its taxonomy and the
      present nomenclature are briefly reviewed. An analysis of the protozoology of the
      most frequent agents is done and, based on the author's own experience and the
      published one, already established anatomo-clinical entities are described: the
      primary amebic meningoencephalitis, granulomatous amebic encephalitis,
      Acanthamoeba keratitis, cutaneous acanthamoebiasis, disseminated infection and
      other rare isolated locations.

PMID- 16896493
TI  - [Pneumocystis jiroveci pneumonia characteristics in adults with AIDS with or
      without antiretroviral therapy].
AB  - Highly active antiretroviral therapy (HAART) has changed the epidemiology of
      Pneumocystis jiroveci pneumonia (PCP) in AIDS patients. Global incidence of PCP
      has decreased and now it is prevalent in AIDS patients who do not receive HAART
      or are unsuccessfully treated with persistent immune depression. Moreover, the
      immunologic response to HAART has caused a PCP form which is included in the
      immune restoration inflammatory syndrome (IRIS). As of late 2004, 75.5% of
      patients cared for at Dr. Lucio Cordova Infectious Diseases Hospital were
      receiving HAART. This study compares PCP clinical characteristics in patients
      under the effect of HAART (n: 6) with those without antiretroviral therapy (n:
      12). Among those with HAART, 83.3% (5/6) were without immunologic responses and
      16.7% with virologic response. The median CD4 counts were low in both groups: 20
      cells/mm(3) without HAART and 51 cells/mm(3) with HAART. There were no
      differences in most of PCP characteristics, and no IRIS cases were observed.
      HAART-receiving group had less severe disease and lower frequency of both,
      complications and steroidal therapy prescription (P 0.023).

PMID- 16896494
TI  - [Genetic variants of Mycobacterium tuberculosis isolated from patients of the Xth
      Region of Chile].
AB  - The emergence of new virulent and drug resistant strains of Mycobacterium
      tuberculosis has forced researchers to focus on the worldwide geographical
      distribution of the genetics variants of this pathogen. Mycobacterium bovis, a
      close related pathogen, contributes with human tuberculosis and therefore, it is
      particularly important in countries with significant bovine tuberculosis
      prevalence. Spoligotyping is currently one of the most widely used strategies for
      genotyping members of the M. tuberculosis complex. In this work, of a total of 41
      isolates, 25 were from different patients from the Xth Region from Chile. These
      isolates formed 15 clusters of spoligotypes. Twenty four percent of the
      spoligotypes corresponded to the worldwide distributed spoligotype 53 (SpolDB4).
      A significant number of spoligotypes were identical to profiles found in Brazil
      followed by Argentina and Spain. Although the patients where from rural areas, no
      cases of zoonosis were observed. To establish the geographical distribution,
      persistence and routes of dissemination of the pathogen, a greater number of
      epidemiologically relevant isolates are being analyzed using the MIRUs-VNTRs.

PMID- 16896495
TI  - [Resistance to antimicrobial drugs in Enterococcus sp. strains isolated in
      hospitals of Northern Chile].
AB  - The prevalence of different species of Enterococcus and the resistance to
      antimicrobial drugs was studied in strains isolated in 5 hospitals of Northern
      Chile. A total of 249 of Enterococcus spp strains were included in this study.
      Enterococci were mostly isolated from urine and wounds. Among five species
      identified, E. faecalis and E. faecium were most frequently isolated in the all
      hospitals. High susceptibility to beta-lactam antibiotics, moderate resistance to
      tetracycline, ciprofloxacin and erythromycin, and high resistance to
      chloramphenicol was observed. Vancomycin resistance was absent. Approximately 12%
      of Enterococcus spp strains presented high level of gentamicin resistance.
      Multiresistance to 3 or more antimicrobial agents was detected in 30% of total
      Enterococcus strains studied.

PMID- 16896496
TI  - [Granulomatous amebic encephalitis caused by Balamuthia mandrillaris. First case
      diagnosed in Chile].
AB  - The case of a 7 month-old baby boy is presented, with a history of several weeks
      of evolution of personality changes, convulsions and fever. While he was
      hospitalized, the brain image study showed multifocal cavity lesions, which
      varied from millimeters to 4 cm of diameter, not producing mass effect. Their
      biopsy revealed necrotizing encephalitis. In spite of treatment, the lesions
      progressed and the boy died. The autopsy demonstrated an extensive necrotizing
      encephalitis with fibrinoid necrotic arteritis, signs of organization, and the
      presence of parasitic elements with characteristics of trophozoites and cysts of
      free-living amoebas belonging to the genus Acanthamoeba or Balamuthia. In
      addition, hypoplasia-dysplasia of the thymus and signs of shock were found. The
      morphologic elements correspond to the disease described as granulomatous amebic
      encephalitis and the agent found was identified as Balamuthia mandrillaris
      (Centers for Diseases Control and Prevention, Atlanta, USA ).

PMID- 16896497
TI  - [Granulomatous amoebic meningoencephalitis by Balamuthia mandrillaris: case
      report and literature review].
AB  - The free-living amebas Naegleria and Acanthamoeba are recognized as causal agents
      of central nervous system infections. Recently a third free-living ameba,
      Balamuthia mandrillaris, was identified as the causal agent of granulomatous
      encephalitis in humans. We report a case of Balamuthia encephalitis in an
      immunocompetent school-age girl who presented cutaneous lesions that compromised
      the central portion of the face. The skin biopsy revealed granulomatous lesion
      with positive PCR for non-tuberculous Mycobacterium. We started treatment for
      atypical extrapulmonary mycobacteriosis. Nevertheless, the child was readmitted
      six months later, with progressive neurological involvement, dying about one year
      after the onset of cutaneous symptoms. The brain necropsy showed the presence of
      B. mandrillaris cysts and trophozoites. Balamuthia mandrillaris infection should
      be considered in the differential diagnosis of a patient with chronic
      granulomatous disease with neurologic symptoms.

PMID- 16896499
TI  - [Stenotrophomonas maltophilia].

PMID- 16896498
TI  - [Pneumococcal endocarditis in children: report of a case due to penicillin
      resistant Streptococcus pneumoniae].
AB  - Despite S. pneumoniae is one of main etiologies of invasive bacterial infection
      in children, it rarely causes infectious endocarditis in children. Pneumococcal
      endocarditis is a serious condition that affects mainly the mitral valve, with a
      rapidly destructive nature and a high fatality rate, demanding prompt medical and
      surgical treatment. We report a case of pneumococcal endocarditis in a school
      girl coming from extreme rurality who presented both meningitis and endocarditis,
      and whose blood cultures isolated penicillin resistant S. pneumoniae.

PMID- 16896500
TI  - [Vaccines under development: Helicobacter pylori].
AB  - Helicobacter pylori causes gastrointestinal disease including peptic ulcer and
      gastric cancer. An H. pylori vaccine is relevant because of the high prevalence
      of the infection and its associated complications. Extensive use of traditional
      antimicrobial therapies to eradicate H. pylori is not feasible, specially in
      developing countries, in part because of their high cost, associated adverse
      effects, the risk of reinfection, and the emergence of antimicrobial drug
      resistance. Numerous animal studies have been performed to determine infection
      outcomes and to explore the feasibility of a vaccine eradication or prevention of
      infection. These animal models with the possible exception of monkeys, have not
      been sufficient to address fundamental issues due to controversial results. A
      human model of H. pylori infection needs to be developed aimed to select an
      optimum vaccine candidate. The ultimate scientific goal will be to develop field
      studies using advanced vaccine candidates, but the current state of knowledge
      does is insufficient and has provided such candidates. These studies need to be
      designed in order to provide relevant information on immunity and pathogenesis
      associated to H. pylori.

PMID- 16896501
TI  - [Pertussis vaccine for adolescents and adults].
AB  - After the introduction of the pertussis vaccine the number of cases decreased
      substantially, albeit, the disease remains present affecting mostly young infants
      in whom it causes severe complications, adolescents and adults. Adults are the
      main reservoir of Bordetella pertussis and serve as vehicle of transmission
      reservoir to infants. The new pertussis vaccines, manufactured for adolescents
      and adults, have good immunogenicity, safety and efficacy (92%) profile. The
      introduction of this vaccine into a universal vaccination program for adolescents
      and adults, would decrease the incidence of the disease in this population and
      more importantly, transmission of the microorganism to infants.

PMID- 16896502
TI  - [Professor Dr. Jose Manuel Borgono Dominguez].

PMID- 16896503
TI  - [Horse of another color].

PMID- 16896505
TI  - Effect of red mold rice supplements on serum and meat cholesterol levels of
      broilers chicken.
AB  - Monacolin K is a secondary metabolite produced by Monascus species. It was found
      that it is able to decrease cholesterol levels. In this study, red mold rice
      (RMR) was added to the diet of Arbor Acres broiler chickens, and the cholesterol
      level in meat, as well as the concentration of triglyceride, the high-density
      lipoprotein cholesterol (HDL-C), and the low-density lipoprotein cholesterol (LDL
      C) in the serum were evaluated. Four-week-old broilers are studied and divided
      into four groups in that each group contains 15 subjects. A 3-week experimental
      feeding trial was conducted in which three groups of broilers were fed 2.0, 5.0,
      and 8.0% of RMR (RMR groups) within their diet, respectively, and the result was
      compared to the control group. The results indicated that for each RMR group, the
      cholesterol content was significantly lower than that of the control group; in
      addition, their meat products contain higher level of unsaturated fatty acids.
      Triglyceride and cholesterol concentration in serum was also found to be
      considerably lower in RMR groups when compared to control group. Finally, in RMR
      groups, HDL-C/LDL-C and HDL-C/cholesterol ratios were all higher than those of
      the control group. In short, the results demonstrated that the cholesterol levels
      could be lowered by adding RMR to the diet of chickens.

PMID- 16896506
TI  - Cr(VI) detoxification by Desulfovibrio vulgaris strain Hildenborough: microbe
      metal interactions studies.
AB  - Toxic heavy metals constitute a worldwide environmental pollution problem.
      Bioremediation technologies represent efficient alternatives to the classic
      cleaning-up of contaminated soil and ground water. Most toxic heavy metals such
      as chromium are less soluble and toxic when reduced than when oxidized. Sulfate
      reducing bacteria (SRB) are able to reduce heavy metals by a chemical reduction
      via the production of H2S and by a direct enzymatic process involving
      hydrogenases and c3 cytochromes. We have previously reported the effects of
      chromate [Cr(VI)] on SRB bioenergetic metabolism and the molecular mechanism of
      the metal reduction by polyhemic cytochromes. In the current work, we pinpoint
      the bacteria-metal interactions using Desulfovibrio vulgaris strain Hildenborough
      as a model. The bacteria were grown in the presence of high Cr(VI) concentration,
      where they accumulated precipitates of a reduced form of chromium, trivalent
      chromium [Cr(III)], on their cell surfaces. Moreover, the inner and outer
      membranes exhibited precipitates that shared the spectroscopic signature of
      trivalent chromium. This subcellular localization is consistent with enzymatic
      metal reduction by cytochromes and hydrogenases. Regarding environmental
      significance, our findings point out the Cr(VI) immobilization mechanisms of SRB;
      suggesting that SRB are highly important in metal biogeochemistry.

PMID- 16896508
TI  - Intravenous pamidronate for pain relief in recent osteoporotic vertebral
      compression fracture: a randomized double-blind controlled study.
AB  - INTRODUCTION: We performed a randomized, double-blind, controlled clinical trial
      comparing intravenous pamidronate and placebo for pain relief in recent
      osteoporotic vertebral compression fractures (VCF). METHODS: Patients suffered
      from recent (<21 days), painful, osteoporosis-related VCF. They were randomized
      to receive daily intravenous infusions of either placebo or 30 mg pamidronate for
      three consecutive days (total pamidronate: 90 mg). The main criterion for
      efficacy was improvement in standing pain on a 100-mm visual analogical scale
      (VAS) at day 7. Secondary criteria were standing pain at days 3 and 30; supine
      pain at days 3, 7, and 30; patients' overall assessment of improvement; mobility
      index; and number of "20% responders" and "50% responders" (respectively, 20% and
      50% improvement in standing pain at days 7 and 30). Statistical analysis with non
      parametric tests was carried out on an intention to treat basis. RESULTS: Thirty
      two patients were enrolled in the study; 16 were given placebo and 16
      pamidronate. Thirty-one patients were evaluated at day 7 and 26 patients at day
      30. VAS pain decreased significantly in both groups at day 7 (placebo -23 mm,
      pamidronate -42 mm, p<0.01). The difference in pain scores between groups was 
      23.25 mm (confidence interval (CI) [-42.3; -4.2], p=0.018) at day 7 and -26 mm at
      day 30 (p=0.03), in favor of pamidronate. At day 7, there were 4 versus 12 "50%
      responders," respectively, in the placebo and in the pamidronate groups
      (likelihood ratio: 8.372; p=0.004) and 9 versus 14 "20% responders" (likelihood
      ratio: 4.038; p=0.044). At day 30, there were 5 versus 10 "50% responders,"
      respectively, in the placebo and in the pamidronate groups, and 7 versus 11 "20%
      responders." Patients' overall assessment of improvement at day 7 was 37+/-26 mm
      in the placebo group and 59+/-30 mm in the pamidronate group (p=0.019), and 42+/
      26 mm and 72+/-21 mm at day 30 (p=0.07). The two groups did not differ
      significantly at days 7 and 30 for supine pain, Schober index, or finger-ground
      distance. No significant adverse reaction related to treatment occurred.
      CONCLUSION: Pamidronate provides rapid and sustained pain relief in patients with
      acute painful osteoporotic VCF and is well tolerated. Further investigations are
      needed to better define the place of pamidronate in the management of painful
      recent osteoporotic collapse.

PMID- 16896507
TI  - Reduction in the risk of developing back pain persists at least 30 months after
      discontinuation of teriparatide treatment: a meta-analysis.
AB  - INTRODUCTION: Teriparatide [rhPTH (1-34)] reduces fracture risk, and in a
      published meta-analysis of clinical trials, teriparatide-treated patients had
      reduced incidence of back pain relative to placebo or to antiresorptive drugs.
      The aim of this study was to evaluate back pain in teriparatide-treated versus
      comparator-treated patients during an interval including controlled clinical
      trials plus 30 months of additional follow-up. METHODS: A meta-analysis of four
      completed randomized, double-blinded trials of teriparatide [rhPTH (1-34)] versus
      comparator was performed. A multivariate Cox proportional hazards model was used
      to assess the heterogeneity of results and to estimate the relative risk of back
      pain. RESULTS: Patients in the pooled teriparatide group had reduced risk for any
      back pain [relative risk, 0.73 (95% CI, 0.61-0.87)], moderate or severe back pain
      [0.72 (0.58-0.89)], and severe back pain [0.39 (0.25-0.61)] compared with pooled
      controls, from initiation of the study drug through the end of follow-up.
      Sensitivity analysis showed that the results were robust to the removal of each
      individual trial from the meta-analysis. Separate meta-analyses comparing
      teriparatide versus placebo or antiresorptive drugs gave similar results.
      CONCLUSIONS: Teriparatide-treated patients had a reduced incidence of back pain
      versus those receiving a comparator during an observation encompassing clinical
      trials plus 30 months of posttreatment observation.

PMID- 16896510
TI  - Factors associated with adherence and persistence to bisphosphonate therapy in
      osteoporosis: a cross-sectional survey.
AB  - OBJECTIVE: To determine the factors associated with adherence and persistence to
      bisphosphonate therapy in osteoporosis. DESIGN: Cross-sectional survey. SETTING:
      National survey in the UK. PARTICIPANTS: Participants were recruited through the
      National Osteoporosis Society and advertisements in the press and on the radio
      and included 533 women over age 50 with osteoporosis who were currently taking or
      had taken bisphosphonate therapy within the previous 12 months. MAIN OUTCOME
      MEASURES: Self-reported factors influencing adherence and persistence to
      bisphosphonate therapy in osteoporosis: fracture history, pain, practical
      difficulties taking medication (frequency of dosing, dealing with comedications,
      impact on daily routine), perceptions of therapy, and concerns about
      bisphosphonate therapy. RESULTS: Adherence to bisphosphonate therapy was 48% and
      was associated with previous fracture [odds ratio (OR) 1.62, 95% confidence
      interval (CI) 1.14-3.02], concerns about medication (OR 1.49, 95% CI 1.01-2.20),
      and less dissatisfaction with medication (OR 0.65, 95% CI 0.44-0.97).
      Nonpersistence was associated with dissatisfaction with medication (hazard ratio
      (HR) 1.83, 95% CI 1.38-2.43), side effects (HR 3.69, 95% CI 2.74-4.97), and
      concerns about bisphosphonate therapy (HR 2.21, 95% CI 1.48-3.30). For both daily
      (HR 1.53, 95% CI 1.1-2.33) and weekly bisphosphonates (HR 1.90, 95% CI 1.17
      3.07), practical difficulties taking bisphosphonate medication-in particular, too
      frequent dosing-were associated with nonpersistence. CONCLUSIONS: Self-reported
      nonadherence to daily and weekly bisphosphonates is independent of the decision
      to stop taking treatment (nonpersistence). Nonpersistence is associated with side
      effects and other factors that could be modified in clinical practice through
      education, information, and concordant partnerships.

PMID- 16896509
TI  - A 19-week exercise program for people with chronic stroke enhances bone geometry
      at the tibia: a peripheral quantitative computed tomography study.
AB  - BACKGROUND: We assessed the impact of a 19-week exercise program on bone health
      in chronic stroke. RESULTS: Those who underwent the program reported
      significantly more gain in tibial trabecular bone content and cortical bone
      thickness on the affected side. CONCLUSION: Regular exercise is thus beneficial
      for enhancing bone health in this population.

PMID- 16896511
TI  - Bone fragility in men--where are we?
AB  - INTRODUCTION: This is a summary of several aspects of the epidemiology,
      pathogenesis and treatment arising directly and indirectly from the proceedings
      of the Third International Osteoporosis in Men meeting held in Genoa in May 2005.
      Advances in the study of bone fragility in men have taken place, but many
      challenges remain. OBSERVATIONS: Although the epidemiology of hip fractures is
      well documented, the epidemiology of other non-vertebral fractures is less well
      defined even though these fractures contribute substantially to the global burden
      of fractures in men. The epidemiology of vertebral fragility fractures is derived
      mostly from cross sectional data. The comparable prevalence of vertebral
      fractures in men and women is likely to be misleading because of traumatic
      vertebral fractures that arise in young men. Prospective studies are needed to
      define the proportion of these fractures that are traumatic. After the age of 50
      years, the incidence of vertebral fractures in men is about one third to one half
      of that in women. As in women, most vertebral and non-vertebral fragility
      fractures occur in persons without osteoporosis. Identifying these individuals is
      an unmet challenge. The absolute risk for fractures appears no different by sex
      in men and women of the same age and bone mineral density (BMD) so that the
      diagnostic threshold for osteoporosis in women can be used in men. Fracture risk
      varies around the world and is unlikely to be explained solely by variations in
      BMD, though there are few data comparing men and women of different races. Both
      the notion that men lose less bone than women from the endosteal envelope and
      that they gain more on the periosteal envelope during advancing age needs
      reassessment as recent evidence challenges these observations. Sex differences in
      the net gain and loss from these surfaces are likely to be site specific, and
      research is needed to specify this heterogeneity and the reasons for it. The
      independent and co-dependent effects of sex hormones and the growth
      hormone/insulin like growth factor 1 axis on periosteal and endosteal modeling
      and remodeling during growth as well as ageing are poorly defined. The anti
      fracture efficacy and safety of androgens and other agents remain incompletely
      investigated in men. CONCLUSION: A great deal of research is needed to advance
      our understanding of bone fragility in men.

PMID- 16896512
TI  - Role of fibroblast growth factor-23 in peripheral vascular calcification in non
      diabetic and diabetic hemodialysis patients.
AB  - INTRODUCTION: Fibroblast growth factor (FGF) 23 is a recently identified
      circulating factor that regulates phosphate (Pi) metabolism. Since the
      derangement of Pi control is an important risk factor for vascular calcification,
      we investigated the importance of plasma FGF-23 in the development of vascular
      calcification in the aorta and peripheral artery in hemodialysis patients with
      and without diabetes mellitus (DM). METHODS: Male hemodialysis patients with DM
      (n=32) and without DM (n=56) were examined. Plasma samples were obtained before
      the start of dialysis sessions, and the FGF-23 levels were determined by enzyme
      linked immunosorbent assay. Roentgenography of the aorta and hand artery was
      performed, and visible vascular calcification was evaluated by one examiner, who
      was blinded to the patient characteristics. RESULTS: In the 56 non-DM
      hemodialysis patients, vascular calcification was found in the hand artery in 5
      patients (8.9%) and in the aorta in 23 patients (41.1%). These levels were
      significantly lower (p<0.05) than in the 32 DM patients, of whom, 19 (59.4%) and
      21 (65.6%) had vascular calcification of the hand artery and aorta, respectively.
      Multiple regression analyses performed separately in the non-DM and DM patients
      showed that the plasma FGF-23 level, CaxPi product, and body weight are
      independent factors significantly associated with hand-artery calcification and
      that diastolic blood pressure is associated with aorta calcification in non-DM
      patients. In DM patients, the plasma FGF-23 level and hemodialysis duration
      emerged as independent factors associated with hand-artery calcification and
      diastolic blood pressure was associated with aorta calcification. The independent
      association of the plasma FGF-23 level with hand-artery calcification was
      retained in both non-DM and DM patients when adjusted for the CaxPi product.
      CONCLUSION: Our findings show that the plasma FGF-23 level is an independent
      factor negatively associated with peripheral vascular calcification in the hand
      artery, but not in the aorta, in both male non-DM and DM hemodialysis patients,
      even when adjusted for the CaxPi product. This study raises the possibility that
      the plasma FGF-23 level may provide a reliable marker for Moenckeberg's medial
      calcification in male hemodialysis patients, independent of its regulatory effect
      on Pi metabolism.

PMID- 16896513
TI  - Correlation of transmenopausal bone mass in healthy white women: a long-term
      longitudinal study.
AB  - INTRODUCTION: It is well established that menopause is associated with
      accelerated bone loss. However, no study has tested whether bone mass after the
      menopause transition is correlated with the premenopausal bone mass; that is,
      whether a high premenopausal bone mass will be predicatively high after menopause
      in an individual. MATERIALS AND METHODS: We examined the association of
      transmenopausal bone mass in 54 healthy premenopausal white women age 46 years or
      older at the initiation. These subjects experienced normal menopause and stayed
      in the study at least 1 year after their last menses without hormone replacement
      therapy. Bone mass of the lumbar spine (L2-L4) and total body were measured
      semiannually for 9.5 years. RESULTS AND DISCUSSION: In the 6-year period for
      which the data were analyzed, we found statistically significant correlations
      (p<0.05) over the 5.5-year and 5-year periods around menopause for pairwise
      transmenopausal lumbar spine Z-score and total body bone mineral content,
      respectively. The correlation declined with increase of the time interval across
      menopause. We conclude that for a limited time interval, bone mass after
      menopause is correlated with that before menopause.

PMID- 16896515
TI  - Fractures in adolescents: comment on article by Konstantynowicz et al.

PMID- 16896516
TI  - Attitudes and illness factors associated with low perceived need for depression
      treatment among young adults.
AB  - BACKGROUND: We do not yet fully understand how low perceived need for treatment
      leads many young adults to not seek care for their depression. METHODS: A cross
      sectional study of 10,962 depressed young adults (ages 16-29) who visited a
      depression screening/education Internet website. Based on the Theory of Reasoned
      Action, we developed a multivariate model to determine the effects of beliefs and
      attitudes, social norms, past treatment behavior, and symptom severity on low
      perceived depression treatment need (i.e., not agreeing that one needs depression
      treatment). RESULTS: Negative beliefs and attitudes, social norms, and past
      treatment behavior predicted low perceived depression treatment need and
      explained more than half the model variance. Even after adjusting for depression
      severity and symptoms of other mental disorders, lacking confidence in either a
      biological or counseling based explanation or treatment approach for depression
      predicted low perceived depression treatment need. CONCLUSIONS: Lack of helpful
      treatment experiences and/or confidence in either of the currently practiced
      depression treatment models may prevent many young adults from seeking depression
      treatment.

PMID- 16896517
TI  - Life events and adjustment following myocardial infarction: a longitudinal study.
AB  - OBJECTIVES: This study examines the implications of both pre-Myocardial
      Infarction (MI) and post-MI life events on the severity of Acute Stress Disorder
      (ASD) and Posttraumatic Stress Disorder (PTSD) symptomatology. METHODS: 116 MI
      patients were examined twice. At Time 1, within a week of the MI, severity of ASD
      and pre-MI life events were assessed, and medical measures were obtained from
      patients' hospital records. At Time 2, seven months later, severity of PTSD and
      post-MI life events were assessed. RESULTS: Although pre-MI life events were
      associated with both ASD and PTSD symptom severity, the relation between these
      events and PTSD was mediated by ASD. Post MI stressful life events made an
      independent contribution to PTSD severity. DISCUSSION: These findings emphasize
      the fact that traumatic events do not occur in isolation and that their emotional
      impact is related to other events that occur both before and after.

PMID- 16896518
TI  - First aid in acute stroke : introducing a concept of first action to laypersons.
AB  - OBJECTIVE: First aid training is well established to teach the public how to
      recognize a medical emergency and take appropriate action. Though it is now
      handled as a high priority emergency stroke is not among the main topics of first
      aid. We investigated if first aid training may be useful for enhancing stroke
      awareness. METHODS: We developed a 15-20 minute teaching session about stroke as
      an emergency including signs and symptoms and first hands-on measures. The
      session was integrated in standard first aid training of the St John Ambulance of
      Germany and participants were asked to fill out a questionnaire regarding their
      knowledge about stroke. Subjects were questioned before the stroke lesson and
      again at the end of the training. RESULTS: 532 participants of the training
      responded to the questionnaire (mean age 28.6 years, 53.6% male). There was a
      significant increase in proportion of subjects correctly defining what stroke is
      (28.4% vs. 69.9%, p < 0,001) and in the mean number of stroke symptoms listed
      (1.52 vs. 3.35, p < 0,001) by the participants. The number of participants unable
      to list at least 1 symptom decreased significantly (12.8 vs. 3.6%, p<0.001).
      CONCLUSIONS: In our study a teaching lesson integrated in first aid training was
      effective in improving stroke knowledge of participants. First aid training
      should be used for stroke information complementary to other activities like mass
      media campaigns as it is effective, could reach younger people that are not
      primarily interested in stroke and provides connections to other health topics.

PMID- 16896519
TI  - How do glutamatergic and GABAergic cells contribute to synchronization in the
      medial septum?
AB  - The medial septum-diagonal band (MSDB) complex is considered as a pacemaker for
      the hippocampal theta rhythm. Identification of the different cell types, their
      electro-physiological properties and their possible function in the generation of
      a synchronized activity in the MSDB is a hot topic. A recent electro
      physiological study showed the presence of two antiphasically firing populations
      of parvalbumin containing GABAergic neurons in the MSDB. Other papers described a
      network of cluster-firing glutamatergic neurons, which is able to generate
      synchronized activity in the MSDB. We propose two different computer models for
      the generation of synchronized population theta oscillation in the MSDB and
      compare their properties. In the first model GABAergic neurons are intrinsically
      theta periodic cluster-firing cells; while in the second model GABAergic cells
      are fast-firing cells and receive periodic input from local glutamatergic neurons
      simulated as cluster-firing cells. Using computer simulations we show that the
      GABAergic neurons in both models are capable of generating antiphasic theta
      periodic population oscillation relying on local, septal mechanisms. In the first
      model antiphasic theta synchrony could emerge if GABAergic neurons form two
      populations preferentially innervate each other. In the second model in-phase
      synchronization of glutamatergic neurons does not require specific network
      structure, and the network of these cells are able to act as a theta pacemaker
      for the local fast-firing GABAergic circuit. Our simulations also suggest that
      neurons being non-cluster-firing in vitro might exhibit clustering properties
      when connected into a network in vivo.

PMID- 16896520
TI  - Differential control of active and silent phases in relaxation models of neuronal
      rhythms.
AB  - Rhythmic bursting activity, found in many biological systems, serves a variety of
      important functions. Such activity is composed of episodes, or bursts (the active
      phase, AP) that are separated by quiescent periods (the silent phase, SP). Here,
      we use mean field, firing rate models of excitatory neural network activity to
      study how AP and SP durations depend on two critical network parameters that
      control network connectivity and cellular excitability. In these models, the AP
      and SP correspond to the network's underlying bistability on a fast time scale
      due to rapid recurrent excitatory connectivity. Activity switches between the AP
      and SP because of two types of slow negative feedback: synaptic depression-which
      has a divisive effect on the network input/output function, or cellular
      adaptation-a subtractive effect on the input/output function. We show that if a
      model incorporates the divisive process (regardless of the presence of the
      subtractive process), then increasing cellular excitability will speed up the
      activity, mostly by decreasing the silent phase. Reciprocally, if the subtractive
      process is present, increasing the excitatory connectivity will slow down the
      activity, mostly by lengthening the active phase. We also show that the model
      incorporating both slow processes is less sensitive to parameter variations than
      the models with only one process. Finally, we note that these network models are
      formally analogous to a type of cellular pacemaker and thus similar results apply
      to these cellular pacemakers.

PMID- 16896521
TI  - Spatio-temporal filtering properties of a dendritic cable with active spines: a
      modeling study in the spike-diffuse-spike framework.
AB  - The spike-diffuse-spike (SDS) model describes a passive dendritic tree with
      active dendritic spines. Spine-head dynamics is modeled with a simple integrate
      and-fire process, whilst communication between spines is mediated by the cable
      equation. In this paper we develop a computational framework that allows the
      study of multiple spiking events in a network of such spines embedded on a simple
      one-dimensional cable. In the first instance this system is shown to support
      saltatory waves with the same qualitative features as those observed in a model
      with Hodgkin-Huxley kinetics in the spine-head. Moreover, there is excellent
      agreement with the analytically calculated speed for a solitary saltatory pulse.
      Upon driving the system with time-varying external input we find that the
      distribution of spines can play a crucial role in determining spatio-temporal
      filtering properties. In particular, the SDS model in response to periodic pulse
      train shows a positive correlation between spine density and low-pass temporal
      filtering that is consistent with the experimental results of Rose and Fortune
      [1999, 'Mechanisms for generating temporal filters in the electrosensory system,'
      The Journal of Experimental Biology 202: 1281-1289]. Further, we demonstrate the
      robustness of observed wave properties to natural sources of noise that arise
      both in the cable and the spine-head, and highlight the possibility of purely
      noise induced waves and coherent oscillations.

PMID- 16896522
TI  - Fast numerical methods for simulating large-scale integrate-and-fire neuronal
      networks.
AB  - We discuss numerical methods for simulating large-scale, integrate-and-fire (I&F)
      neuronal networks. Important elements in our numerical methods are (i) a
      neurophysiologically inspired integrating factor which casts the solution as a
      numerically tractable integral equation, and allows us to obtain stable and
      accurate individual neuronal trajectories (i.e., voltage and conductance time
      courses) even when the I&F neuronal equations are stiff, such as in strongly
      fluctuating, high-conductance states; (ii) an iterated process of spike-spike
      corrections within groups of strongly coupled neurons to account for spike-spike
      interactions within a single large numerical time-step; and (iii) a clustering
      procedure of firing events in the network to take advantage of localized
      architectures, such as spatial scales of strong local interactions, which are
      often present in large-scale computational models-for example, those of the
      primary visual cortex. (We note that the spike-spike corrections in our methods
      are more involved than the correction of single neuron spike-time via a
      polynomial interpolation as in the modified Runge-Kutta methods commonly used in
      simulations of I&F neuronal networks.) Our methods can evolve networks with
      relatively strong local interactions in an asymptotically optimal way such that
      each neuron fires approximately once in [Formula: see text] operations, where N
      is the number of neurons in the system. We note that quantifications used in
      computational modeling are often statistical, since measurements in a real
      experiment to characterize physiological systems are typically statistical, such
      as firing rate, interspike interval distributions, and spike-triggered voltage
      distributions. We emphasize that it takes much less computational effort to
      resolve statistical properties of certain I&F neuronal networks than to fully
      resolve trajectories of each and every neuron within the system. For networks
      operating in realistic dynamical regimes, such as strongly fluctuating, high
      conductance states, our methods are designed to achieve statistical accuracy when
      very large time-steps are used. Moreover, our methods can also achieve trajectory
      wise accuracy when small time-steps are used.

PMID- 16896523
TI  - An extracellular halophilic protease SptA from a halophilic archaeon Natrinema
      sp. J7: gene cloning, expression and characterization.
AB  - A gene encoding an extracellular protease, sptA, was cloned from the halophilic
      archaeon Natrinema sp. J7. It encoded a polypeptide of 565 amino acids containing
      a putative 49-amino acid signal peptide, a 103-amino acid propeptide, as well as
      a mature region and C-terminal extension, with a high proportion of acidic amino
      acid residues. The sptA gene was expressed in Haloferax volcanii WFD11, and the
      recombinant enzyme could be secreted into the medium as an active mature form.
      The N-terminal amino acid sequencing and MALDI-TOF mass spectrometry analysis of
      the purified SptA protease indicated that the 152-amino acid prepropeptide was
      cleaved and the C-terminal extension was not processed after secretion. The SptA
      protease was optimally active at 50 degrees C in 2.5 M NaCl at pH 8.0. The NaCl
      removed enzyme retained 20% of its activity, and 60% of the activity could be
      restored by reintroducing 2.5 M NaCl into the NaCl removed enzyme. When the twin
      arginine motif in the signal peptide of SptA protease was replaced with a twin
      lysine motif, the enzyme was not exported from Hfx. volcanii WFD11, suggesting
      that the SptA protease was a Tat-dependent substrate.

PMID- 16896525
TI  - Characterisation of the novel restriction endonuclease SuiI from Sulfolobus
      islandicus.
AB  - A restriction endonuclease activity from Sulfolobus islandicus REN2H1 was
      purified by phosphocellulose and cation exchange chromatography. The enzyme cuts
      DNA at the recognition site GCwGC as could be shown by restriction analysis of
      plasmids and short synthetic duplex DNA. The cleavage occurs after the first
      guanosine base and is inhibited by 5-methyl-cytosine methylation. The restriction
      activity is salt-sensitive and has an optimal activity around 70 degrees C.

PMID- 16896526
TI  - Characterization of the Sulfolobus host-SSV2 virus interaction.
AB  - The Sulfolobus spindle virus, SSV2, encodes a tyrosine integrase which furthers
      provirus formation in host chromosomes. Consistently with the prediction made
      during sequence analysis, integration was found to occur in the downstream half
      of the tRNA(Gly) (CCC) gene. In this paper we report the findings of a
      comparative study of SSV2 physiology in the natural host, Sulfolobus islandicus
      REY15/4, versus the foreign host, Sulfolobus solfataricus, and provide evidence
      of differently regulated SSV2 life cycles in the two hosts. In fact, whereas a
      significant induction of SSV2 replication takes place during the growth of the
      natural host REY15/4, the cellular content of SSV2 DNA remains fairly low
      throughout the incubation of the foreign host. The accumulation of episomal DNA
      in the former case cannot be traced to decreased packaging activity because of a
      simultaneous increase in the virus titre in the medium. In addition, the
      interaction between SSV2 and its natural host is characterized by the concurrence
      of host growth inhibition and the induction of viral DNA replication. When this
      virus-host interaction was investigated using S. islandicus REY15A, a strain
      which is closely related to the natural host, it was found that the SSV2
      replication process was induced in the same way as in the natural host REY15/4.

PMID- 16896524
TI  - Microarray analysis of the hyperthermophilic archaeon Pyrococcus furiosus exposed
      to gamma irradiation.
AB  - The remarkable survival of the hyperthermophilic archaeon Pyrococcus furiosus to
      ionizing radiation was previously demonstrated. Using a time course study and
      whole-genome microarray analyses of mRNA transcript levels, the genes and
      regulatory pathways involved in the repair of lesions produced by ionizing
      irradiation (oxidative damage and DNA strand breaks) in P. furiosus were
      investigated. Data analyses showed that radA, encoding the archaeal homolog of
      the RecA/Rad51 recombinase, was moderately up regulated by irradiation and that a
      putative DNA-repair gene cluster was specifically induced by exposure to ionizing
      radiation. This novel repair system appears to be unique to thermophilic archaea
      and bacteria and is suspected to be involved in translesion synthesis. Genes that
      encode for a putative Dps-like iron-chelating protein and two membrane-bound
      oxidoreductases were differentially expressed following gamma irradiation,
      potentially in response to oxidative stress. Surprisingly, the many systems
      involved in oxygen detoxification and redox homeostasis appeared to be
      constitutively expressed. Finally, we identified several transcriptional
      regulators and protein kinases highly regulated in response to gamma irradiation.

PMID- 16896527
TI  - Functional similarities of a thermostable protein-disulfide oxidoreductase
      identified in the archaeon Pyrococcus horikoshii to bacterial DsbA enzymes.
AB  - We have isolated and characterized a gene for a putative protein-disulfide
      oxidoreductase (phdsb) in the archaeon Pyrococcus horikoshii. The open reading
      frame of phdsb encodes a protein of 170 amino acids with an NH(2)-terminal
      extension similar to the bacterial signal peptides. The putative mature region of
      PhDsb includes a sequence motif, Cys-Pro-His-Cys (CPHC), that is conserved in
      members of the bacterial DsbA family, but otherwise the archaeal and bacterial
      sequences do not show substantial similarity. A recombinant protein corresponding
      to the predicted mature form of PhDsb behaved as a monomer and manifested
      oxidoreductase activities in vitro similar to those of DsbA of Escherichia coli.
      The catalytic activity of PhDsb was thermostable and was shown by mutation
      analysis to depend on the NH(2)-terminal cysteine residue of the CPHC motif.
      Thus, in spite of their low overall sequence similarities, DsbA-like proteins of
      archaea and bacteria appear to be highly similar in terms of function.

PMID- 16896528
TI  - A highly thermostable, homodimeric single-stranded DNA-binding protein from
      Deinococcus radiopugnans.
AB  - We report the identification and characterization of the single-stranded DNA
      binding protein (SSB) from the mesophile and highly radiation-resistant
      Deinococcus radiopugnans (DrpSSB). PCR-derived DNA fragment containing the
      complete structural gene for DrpSSB protein was cloned and expressed in
      Escherichia coli. The gene consisting of an open reading frame of 900 nucleotides
      encodes a protein of 300 amino acids with a calculated molecular weight of 32.45
      kDa and pI 5.34. The amino acids sequence exhibits 43, 44, 79 and 18% identity
      with Thermus aquaticus, Thermus thermophilus, Deinococcus radiodurans and E. coli
      SSBs, respectively. The DrpSSB includes two OB folds per monomer and functions as
      a homodimer. In fluorescence titrations with poly(dT), DrpSSB bound 24-31 nt
      depending on the salt concentration, and fluorescence was quenched by about 80%.
      In a complementation assay in E. coli, DrpSSB took over the in vivo function of
      EcoSSB. The half-lives of DrpSSB were 120 min at 90 degrees C, 60 min at 95
      degrees C and 30 min at 100 degrees C. These results were surprising in the
      context of half-life of SSB from thermophilic T. aquaticus, which has only 30 s
      of half-life at 95 degrees C. DrpSSB is the most thermostable SSB-like protein
      identified to date, offering an attractive alternative for TaqSSB and TthSSB in
      their applications for molecular biology methods and analytical purposes.

PMID- 16896529
TI  - Thermonasty of young main stems of Phryma leptostachya (Phrymaceae).
AB  - Thermonasty-like responses were observed on some main stems of Phryma
      leptostachya (Phrymaceae) plants cultivated in the open. To confirm the
      thermonastic nature of these responses, the plants were moved into an
      artificially illuminated chamber and observed under controlled conditions. At low
      temperatures (about 12 degrees C) and in the dark, slanted terrestrial young main
      stems of P. leptostachya became prostrate. At higher temperatures (about 25
      degrees C) and in the dark, the prostrate stems became slanted. Their movement
      was confirmed under controlled conditions and is therefore considered to be
      thermonastic in nature.

PMID- 16896531
TI  - Wide-band tracheids in genera of Portulacaceae: novel, non-xylary tracheids
      possibly evolved as an adaptation to water stress.
AB  - Wide-band tracheids (WBTs) are novel tracheids with wide, lignified secondary
      walls that intrude deeply into the cell lumen when viewed in transverse sections.
      These tracheids are found in a few genera in related families in the order
      Caryophyllales: Aizoaceae, Cactaceae, and Portulacaceae. WBTs in these three
      families vary in (1) systematic occurrence (found in more highly derived genera
      in each family), (2) location in plant organs, and (3) structure and dimensions.
      In addition, an analysis was conducted of WBT cell walls to test the hypothesis
      that WBTs evolved as an adaptation to water stress (i.e., the wide secondary
      walls should prevent collapse of the primary wall during water stress). The cell
      wall data show that primary cell walls in WBTs cannot inwardly collapse to
      occlusion, thus providing support for the water stress hypothesis of WBT
      evolution. With consideration of their systematic occurrence, the molecular
      phylogenetic data, and data here showing support for a water stress adaptive
      origin, it is logical to assume that WBTs evolved in genera that were adapting to
      environments undergoing a rapid trend toward aridification.

PMID- 16896530
TI  - Molecular cloning and differential expression of an gamma-aminobutyrate
      transaminase gene, OsGABA-T, in rice (Oryza sativa) leaves infected with blast
      fungus.
AB  - gamma-Aminobutyrate transaminase (GABA-T) catalyzes the conversion of GABA to
      succinic semialdehyde. Using differential display PCR and cDNA library screening,
      a full-length GABA-T cDNA (OsGABA-T) was isolated from rice (Oryza sativa) leaves
      infected with an incompatible race of Magnaporthe grisea. The deduced amino acid
      sequence comprises 483 amino acid residues and shares 85-69% identity with GABA-T
      sequences from other plants. OsGABA-T expression is induced by blast fungus
      infection, mechanical wounding and ultraviolet radiation in rice leaves and is
      not detected in normal rice organs. This gene is also induced by defense signal
      molecules such as salicylic acid and abscisic acid, but not by jasmonic acid. Our
      data suggest that OsGABA-T (GABA shunt) may play a role in restricting the levels
      of cell death during the host-pathogen interaction.

PMID- 16896532
TI  - Gene polymorphisms for elucidating the genetic structure of the heavy-metal
      hyperaccumulating trait in Thlaspi caerulescens and their cross-genera
      amplification in Brassicaceae.
AB  - Genetic polymorphism was investigated in Thlaspi caerulescens J. & C. Presl at 15
      gene regions, of which seven have been identified to putatively play a role in
      heavy-metal tolerance or hyperaccumulation. Single nucleotide and length
      polymorphisms were assessed at four cleaved amplified polymorphic sequences
      (CAPS) and 11 simple sequence repeat (microsatellite) loci, respectively. The
      utility of these loci for genetic studies in T. caerulescens was measured among
      seven natural populations (135 individuals). Fourteen loci rendered polymorphism,
      and the number of alleles per locus varied from 2 to 5 and 1 to 27 for CAPS and
      microsatellites, respectively. Up to 12 alleles per locus were detected in a
      population. The global observed heterozygosity per population varied between 0.01
      and 0.31. Additionally, cross-species/genera amplification of loci was
      investigated on eight other Brassicaceae (five individuals per population).
      Overall, 70% of the cross-species/genera amplifications were successful, and
      among them, more than 40% provided intraspecific polymorphisms within a single
      population. This indicates that such markers may, as well, allow comparative
      population genetic or mapping studies between and within several Brassicaceae,
      particularly for genes involved in traits such as heavy-metal tolerance and/or
      hyperaccumulation.

PMID- 16896533
TI  - New resources for marine genomics: bacterial artificial chromosome libraries for
      the Eastern and Pacific oysters (Crassostrea virginica and C. gigas).
AB  - Large-insert genomic bacterial artificial chromosome (BAC) libraries of two
      culturally and economically important oyster species, Crassostrea virginica and
      C. gigas, have been developed as part of an international effort to develop tools
      and reagents that will advance our ability to conduct genetic and genomic
      research. A total of 73,728 C. gigas clones with an average insert size of 152 kb
      were picked and arrayed representing an 11.8-fold genome coverage. A total of
      55,296 clones with an average insert size of 150 kb were picked and arrayed for
      C. virginica, also representing an 11.8-fold genome coverage. The C. gigas and C.
      virginica libraries were screened with probes derived from selected oyster genes
      using high-density BAC colony filter arrays. The probes identified 4 to 25 clones
      per gene for C. virginica and 5 to 50 clones per gene for C. gigas. We conducted
      a preliminary analysis of genetic polymorphism represented in the C. gigas
      library. The results suggest that the degree of divergence among similar
      sequences is highly variable and concentrated in intronic regions. Evidence
      supporting allelic polymorphism is reported for two genes and allelic and/or
      locus specific polymorphism for several others. Classical inheritance studies are
      needed to confirm the nature of these polymorphisms. The oyster BAC libraries are
      publicly available to the research community on a cost-recovery basis at
      (www.genome.clemson.edu).

PMID- 16896534
TI  - Analysis of expressed sequence tags from the harmful alga, Prymnesium parvum
      (Prymnesiophyceae, Haptophyta).
AB  - A cDNA library was constructed from late log-phase cultures of the ichthyotoxin
      producing haptophyte, Prymnesium parvum. Approximately 6,300 single-pass 5'
      nucleotide sequences (out of nearly 8,000 randomly isolated clones) achieved
      length and quality criteria for incorporation into an expressed sequence tag
      (EST) database. Collectively, 3,415 unique genes (tentative unigenes [TUGs]) were
      assembled. Database searches revealed approximately 1,100 TUG (34%) that encode
      proteins of known or putative function (expect values E < or = 1.0 x 10(-10)),
      representing most functional classes of proteins and many metabolic pathways. In
      addition to proteins involved in photosynthesis and protein
      synthesis/degradation, one of the most frequently encountered transcripts
      putatively encodes an ABC-type phosphate transport system component. Active (and
      efficient?) phosphate transport may correlate with rapid growth, perhaps
      explaining how this alga out-competes other species when it blooms and becomes
      toxic under low-phosphate conditions. The majority of TUGs, including 12 of the
      50 most commonly encountered transcripts, encode potentially novel proteins, some
      of which are probably involved in synthesis and secretion of the unique prymnesin
      toxins. This work suggests that future studies on the expression of many of these
      genes during rapid growth should provide insight into the genetic basis of bloom
      formation and toxicity.

PMID- 16896536
TI  - The NADPH- and iron-dependent lipid peroxidation in human placental microsomes.
AB  - In pregnant females, placenta is the most important source of lipid
      hydroperoxides and other reactive oxygen species (ROS). The increased production
      of lipid peroxides is often linked to preeclampsia. In our study, we revealed
      that NADPH- and iron-dependent lipid peroxidation in human placental microsomes
      (HPM) occurred. In the presence of Fe2+ ion, HPM produced small amounts of
      thiobarbituric acid-reactive substances (TBARS) - a final product of lipid
      peroxidation. NADPH caused a strong increase of iron stimulated TBARS formation.
      TBARS formation was inhibited by superoxide dismutase, butylated hydroxytoluene
      and alpha-tocopherol but not by mannitol or catalase. TBARS and superoxide
      radical production was inhibited in similar manner by cytochrome P450 inhibitors.
      The results obtained led us to the following conclusions: (1) microsomal lipid
      peroxidation next to mitochondrial lipid peroxidation may by an important source
      of lipid hydroperoxides in blood during pregnancy and (2) superoxide radical
      released by microsomal cytochrome P450 is an important factor in NADPH- and iron
      dependent lipid peroxidation in HPM.

PMID- 16896535
TI  - Lysophosphatidylcholine induces inflammatory activation of human coronary artery
      smooth muscle cells.
AB  - Lysophosphatidylcholine (LPC) is the major bioactive lipid component of oxidized
      LDL, thought to be responsible for many of the inflammatory effects of oxidized
      LDL described in both inflammatory and endothelial cells. Inflammation-induced
      transformation of vascular smooth muscle cells from a contractile phenotype to a
      proliferative/secretory phenotype is a hallmark of the vascular remodeling that
      is characteristic of atherogenesis; however, the role of LPC in this process has
      not been fully described. The present study tested the hypothesis that LPC is an
      inflammatory stimulus in coronary artery smooth muscle cells (CASMCs). In
      cultured human CASMCs, LPC stimulated time- and concentration-dependent release
      of arachidonic acid that was sensitive to phospholipase A2 and C inhibition. LPC
      stimulated the release of arachidonic acid metabolites leukotriene-B4 and 6-keto
      prostaglandin F1alpha, within the same time course. LPC was also found to
      stimulate basic fibroblast growth factor release as well as stimulating the
      release of the cytokines GM-CSF, IL-6, and IL-8. Optimal stimulation of these
      signals was obtained via palmitic acid-substituted LPC species. Stimulation of
      arachidonic acid, inflammatory cytokines and growth factor release, implies that
      LPC might play a multifactorial role in the progression of atherosclerosis, by
      affecting inflammatory processes.

PMID- 16896537
TI  - Temporal variation in the expression of the p53 protein in proliferating and
      differentiating murine erythroleukaemia cells.
AB  - Temporal changes in the expression of p53 were investigated during hexamethylene
      bisacetamide (HMBA)-induced differentiation of murine erythroleukaemic (MEL)
      cells. Cell preparations were analysed by SDS-PAGE and western immunoblotting,
      which detected an immunospecific band of molecular mass 53 kDa. This analysis
      provided semi-quantitative information. Cell extracts were analysed further by
      means of ELISA techniques, using a p53-specific antibody, to provide quantitative
      data. In time series experiments in which cells were isolated at 15, 30 and 60
      min intervals, dynamic variations in the expression of the p53 protein were
      detected in both the untreated and the HMBA-treated MEL cells. In all cases, the
      effects were complex with variations in amplitude, frequency and phasing of the
      rhythms. The available evidence suggests that the observed patterns, like
      periodic variations in other systems, are modified in rhythmic fashion with
      respect to period and amplitude. The results add further support for our view
      that it is essential to consider the dynamics when interpreting the role of p53
      and cellular processes in general.

PMID- 16896538
TI  - Therapeutic efficacy of Kalpaamruthaa on reactive oxygen/nitrogen species levels
      and antioxidative system in mammary carcinoma bearing rats.
AB  - Reactive oxygen species play an important role in cancer and metastasis.
      Kalpaamruthaa is a modified Siddha preparation, which has been formulated in our
      laboratory. The preparation is an amalgamation of Semecarpus anacardium (SA),
      Emblica officinalis (EO) and honey, which gives an extra protectiveness to
      mammary carcinoma bearing animals (Sprague-Dawley stains were used for this
      study). The aim of our research is to determine the therapeutic efficiency of the
      drug with respect to lipid peroxidation and antioxidant status. The levels of
      lipid peroxides and antioxidant levels were measured in blood, and vital organs
      (liver, kidney and breast tissue) of control and experimental animals. In cancer
      condition, the LPO was increased and antioxidant levels were decreased. On drug
      (SA and KA) administration, decreased LPO and increased antioxidant levels were
      seen in control and experimental animals. This may be due to additive property of
      the drugs (SA, Emblica and honey), which possesses anticancer effect. The present
      study shows the good therapeutic efficacy of Kalpaamruthaa against mammary
      carcinoma.

PMID- 16896539
TI  - Age- and cell cycle-dependent changes in EPC-1/PEDF promoter activity in human
      diploid fibroblast-like (HDF) cells.
AB  - The changes in gene expression during senescence are very interesting. Early
      population doubling cDNA-1 (EPC-1, also known as pigment epithelial derived
      factor, PEDF) is one of the genes whose expression decreases dramatically during
      cellular aging. We examined whether or not EPC-1/PEDF promoter activity was
      affected by the cellular ageing using human diploid lung fibroblast cells in
      culture. Here we showed the promoter/enhancer region of EPC-1/PEDF existed at
      more than 1760 bp upstream from the transcriptional initiation site of the gene,
      and was regulated by both aging and cell cycle. These findings suggest that the
      expression of the EPC-1/PEDF gene is, at least in part, regulated
      transcriptionally in the cells. The analysis of the promoter region of the EPC
      1/PEDF gene in this paper suggests the age- and cell cycle-dependent expression
      of specific transcriptional factor(s).

PMID- 16896540
TI  - Impaired long-chain fatty acid metabolism in mitochondria causes brain vascular
      invasion by a non-neurotropic epidemic influenza A virus in the newborn/suckling
      period: implications for influenza-associated encephalopathy.
AB  - The neuropathogenesis of influenza-associated encephalopathy in children and
      Reye's syndrome remains unclear. A surveillance effort conducted during 2000-2003
      in South-West Japan reveals that almost all fatal and handicapped influenza
      associated encephalopathy patients exhibit a disorder of mitochondrial beta
      oxidation with elevated serum acylcarnitine ratios (C(16:0)+C(18:1))/C(2). Here
      we show invasion by a non-neurotropic epidemic influenza A H3N2 virus in cerebral
      capillaries with progressive brain edema after intranasal infection of mice
      having impaired mitochondrial beta-oxidation congenitally or posteriorly in the
      newborn/ suckling periods. Mice genetically lacking of carnitine transporter
      OCTN2, resulting in carnitine deficiency and impaired beta-oxidation, exhibited
      significant higher virus-genome numbers in the brain, accumulation of virus
      antigen exclusively in the cerebral capillaries and increased brain vascular
      permeability compared to in wild type mice. Mini-plasmin, which proteolytically
      potentiates influenza virus multiplication in vivo and destroys the blood-brain
      barrier, accumulated with virus antigen in the brain capillaries of OCTN2
      deficient mice but only a little in wild-type mice. These results suggest that
      the impaired mitochondrial beta-oxidation changes the susceptibility to a non
      neurotropic influenza A virus as to multiplication in the brain capillaries and
      to cause brain edema. These pathological findings in the brain of mice having
      impaired mitochondrial beta-oxidation after influenza virus infection may have
      implications for human influenza-associated encephalopathy.

PMID- 16896541
TI  - V-cluster algorithm: a new algorithm for clustering molecules based upon numeric
      data.
AB  - Clustering molecules based on numeric data such as, gene-expression data,
      physiochemical properties, or theoretical data is very important in drug
      discovery and other life sciences. Most approaches use hierarchical clustering
      algorithms, non-hierarchical algorithms (for examples, K-mean and K-nearest
      neighbor), and other similar methods (for examples, the Self-Organization Mapping
      (SOM) and the Support Vector Machine (SVM)). These approaches are non-robust
      (results are not consistent) and, computationally expensive. This paper will
      report a new, non-hierarchical algorithm called the V-Cluster (V stands for
      vector) Algorithm. This algorithm produces rational, robust results while
      reducing computing complexity. Similarity measurement and data normalization
      rules are also discussed along with case studies. When molecules are represented
      in a set of numeric vectors, the V-Cluster Algorithm clusters the molecules in
      three steps: (1) ranking the vectors based upon their overall intensity levels,
      (2) computing cluster centers based upon neighboring density, and (3) assigning
      molecules to their nearest cluster center. The program is written in C/C++
      language, and runs on Window95/NT and UNIX platforms. With the V-Cluster program,
      the user can quickly complete the clustering process and, easily examine the
      results by use of thumbnail graphs, superimposed intensity curves of vectors, and
      spreadsheets. Multi-functional query tools have also been implemented.

PMID- 16896542
TI  - Advances in microwave-assisted combinatorial chemistry without polymer-supported
      reagents.
AB  - Combinatorial methodologies have dramatically changed the chemical research and
      discovery process, offering an unlimited source of new molecule entities to be
      screened for activity. The application of microwave irradiation in Combinatorial
      Chemistry and high-throughput synthesis has become increasingly popular. By
      taking advantage of this energy source, compound libraries for lead generation
      can be assembled in a fraction of time required by conventional thermal heating.
      This review focuses on the advances in developing synthetic methodologies in
      microwave without polymer-supported reagents suitable for combinatorial
      chemistry, including the advances in microwave-assisted fluorous synthesis
      technology.

PMID- 16896543
TI  - Use of 4-bromo pyridazine 3,6-dione for building 3-amino pyridazine libraries.
AB  - An efficient method for preparation of 4,6 or 5,6 disubstituted 3
      aminopyridazines was easily carried out starting from easily available 4-bromo
      pyridazine-3,6-dione, and using combination of both amination and Pd(0) cross
      coupling reactions under microwave irradiation.

PMID- 16896544
TI  - On an aspect of calculated molecular descriptors in QSAR studies of quinolone
      antibacterials.
AB  - The re-emergence of tuberculosis infections, which are resistant to conventional
      drug therapy, has steadily risen in the last decade and as a result of that,
      fluoroquinolone drugs are being used as the second line of action. But there is
      hardly any study to examine specific structure activity relationships of
      quinolone antibacterials against mycobacteria. In this paper, an attempt has been
      made to establish a quantitative structure activity relationship modeling for a
      series of quinolone compounds against Mycobacterium fortuitum and Mycobacterium
      smegmatis. Due to lack of sufficient physicochemical data for the anti
      mycobacterial compounds, it becomes very difficult to develop predictive methods
      based on experimental data. The present paper is an effort for the development of
      QSARs from the standpoint of physicochemical, constitutional, geometrical,
      electrostatic and topological indices. Molecular descriptors have been calculated
      solely from the chemical structure of N-1, C-7 and 8 substituted quinolone
      compounds and ridge regression models have been developed which can explain a
      better structure-activity relationship. Consideration of an intermolecular
      similarity analysis approach that led to a successful computer program
      development in PERL language has been used for comparing the influence of various
      molecular descriptors in different data subsets. The comparison of relative
      effectiveness of the calculated descriptors in our ridge regression model gives
      rise to some interesting results.

PMID- 16896545
TI  - A novel simple QSAR model for the prediction of anti-HIV activity using multiple
      linear regression analysis.
AB  - A quantitative-structure activity relationship was obtained by applying Multiple
      Linear Regression Analysis to a series of 80 1-[2-hydroxyethoxy-methyl]-6
      (phenylthio) thymine (HEPT) derivatives with significant anti-HIV activity. For
      the selection of the best among 37 different descriptors, the Elimination
      Selection Stepwise Regression Method (ES-SWR) was utilized. The resulting QSAR
      model (R (2) (CV) = 0.8160; S (PRESS) = 0.5680) proved to be very accurate both
      in training and predictive stages.

PMID- 16896546
TI  - Genes and longevity: a genetic-demographic approach reveals sex- and age-specific
      gene effects not shown by the case-control approach (APOE and HSP70.1 loci).
AB  - Association analyses between gene variability and human longevity carried out by
      comparing gene frequencies between population samples of different ages
      (case/control design) may provide information on genes and pathways playing a
      role in modulating survival at old ages. However, by dealing with cross-sectional
      data, the gene-frequency (GF) approach ignores cohort effects in population
      mortality changes. The genetic-demographic (GD) approach adds demographic
      information to genetic data and allows the estimation of hazard rates and
      survival functions for candidate alleles and genotypes. Thus mortality changes in
      the cohort to which the cross-sectional sample belongs are taken into account. In
      this work, we applied the GD method to a dataset relevant to two genes, APOE and
      HSP70.1, previously shown to be related to longevity by the GF method. We show
      that the GD method reveals sex- and age-specific allelic effects not shown by the
      GF analysis. In addition, we provide an algorithm for the implementation of a non
      parametric GD analysis.

PMID- 16896547
TI  - Extent of atherosclerosis and prognosis of patients with aneurysmal subarachnoid
      haemorrhage.
AB  - BACKGROUND AND PURPOSE: Atherosclerosis impairs the endothelial dependent
      vasodilatation and may change the diameter and plasticity of cerebral vessels.
      The aim of this study was to investigate if an index of the occurrence of
      atherosclerosis is associated with the risk of delayed cerebral ischemia or poor
      outcome after subarachnoid haemorrhage. METHODS: To assess the likelihood of
      atherosclerosis we used a modified version of the Framingham Heart Study Coronary
      Heart Disease Prediction Chart. The relation of this index to the occurrence of
      delayed cerebral ischemia was studied by means of survival analysis and to poor
      outcome by regression analysis. A multivariate analysis was used to investigate
      the independent contribution of the atherosclerosis index. RESULTS: Three hundred
      and twenty three patients were retrieved from our database from the period 1997
      to 2004. The index of atherosclerosis related to a good clinical condition on
      admission (p = 0.01). A high risk of atherosclerosis independently predicted poor
      outcome (OR 4.3; 95%CI 1.6-12). This was not caused by an increase in the
      occurrence of delayed cerebral ischemia (HR 1.1; 95%CI 0.6-2.1), but, in part, by
      a marked decrease in recurrent bleeding in patients with no or minor
      atherosclerosis. CONCLUSIONS: An index of the occurrence of atherosclerosis is
      related to prognosis after subarachnoid haemorrhage. The use of the score may
      focus attention on patients at risk for poor outcome after subarachnoid
      haemorrhage.

PMID- 16896548
TI  - Multiple mirror-like intracranial aneurysms. Report of a case and review of the
      literature.
AB  - While multiple intracranial arterial aneurysms occur in 26.4% of patients with
      aneurysms, in our practice bilateral mirror-like aneurysms are encountered in
      9.4% of patients. Multiple mirror aneurysms in the same patient are exceedingly
      rare. We report a case of mirror-like middle cerebral artery aneurysms associated
      with mirror-like posterior inferior cerebellar arteries aneurysms and discuss
      their significance. Although an exceptional finding, multiple mirror-like
      aneurysms may shed light on the vulnerability of different arterial segments to
      specific diseases.

PMID- 16896549
TI  - Frequency of antibodies against E4 and E7 from human papillomavirus type 16 in
      Mexican soldiers.
AB  - The high prevalence of HPV in men's genitalia and the low frequency of virus
      associated lesions gave rise to questions on the influence of infection-site on
      the HPV antibody profile. In a cross-sectional study, HPV infection in penis and
      urethra, and serum antibodies against HPV-16 E4 and E7 proteins were evaluated in
      288 Mexican soldiers. The results showed that HPV prevalence was 31% (51% in
      penis, 11% in urethra and 38% in both sites), while 47% were multiple infections.
      Overall, seroprevalence was 13% for anti-E4 antibodies and 6% for anti-E7.
      However, the highest prevalence of anti-E4 antibodies was observed in men with
      HPV infection in urethra (30%), while for E7 antibodies, the highest prevalence
      (10%) was found in men who tested positive for HPV in penis. The prevalence of
      IgG and IgA anti-E4 was related to HPV-16 urethral infection, while detection of
      HPV-16 in penis was related to IgG anti-E7 prevalence. In conclusion, the high
      risk sexual behavior observed in this population might be responsible for high
      HPV prevalence and multiple infections. However, the seroprevalence of E4 and E7
      was similar to that observed in healthy Mexican women. These results suggest that
      the humoral immune response against HPV infection in men differs, depending on
      the site of infection.

PMID- 16896550
TI  - High HPV genetic diversity in women infected with HIV-1 in Brazil.
AB  - The present study on genetic diversity of human papillomaviruses in women
      infected by HIV in Brazil describes the frequency, the genotypes, and five new
      variants of HPV. One hundred fifty cervical smears of HIV-positive women were
      subjected to cytological examination, and the DNA samples obtained were assayed
      by MY09/MY11 amplification, followed by RFLP typing. The overall HPV-DNA-positive
      rate was 42.7%. One hundred twenty-two samples (81.3%) had benign cellular
      alterations or normal cytological results, and HPV DNA frequency among them was
      30.3%. Otherwise, 96.4% of samples with altered cytology were positive for HPV
      DNA. A high diversity of genotypes was observed. HPVs-16 and 81 were the most
      prevalent (14.1%) and were followed by HPVs 52, 35, 62, 33, 53, 56, 66, 70, 18,
      58, 6b, 11, 31, 39, 40, 61, 71, 32, 54, 59, 67, 68, 85, and 102. Five new
      variants of the high-risk HPVs 18, 33, 53, 59, and 66 were detected. Possible
      associations between the detection of HPV genotypes and the cytological
      classification, HIV viral load, CD4 count, and antiretroviral treatment were also
      examined. We observed that a high proportion of HIV-infected women are infected
      with HPV and may carry oncogenic genotypes, even when cytological evaluation
      shows normal results.

PMID- 16896551
TI  - The relationship between polymorphisms of HCMV UL144 ORF and clinical
      manifestations in 73 strains with congenital and/or perinatal HCMV infection.
AB  - Human cytomegalovirus (HCMV) displays genetic variability and can cause a wide
      range of diseases in neonates. To explore the relationship between polymorphisms
      and clinical manifestations, the UL144 genes from 73 clinical strains were
      sequenced. All of the strains, which came from 70 infants with suspected
      congenital and/or perinatal HCMV infection, were non-passage strains. Among them,
      23 strains were from surgery specimens, and the others were from urine samples.
      Clinically, 12 infants displayed asymptomatic infection and 58 patients displayed
      symptomatic infection. The results showed that 36 patients (49.3%) were infected
      with strains belonging to UL144 group G1 (G1a 33/36, G1b 3/36), 19 patients
      (28.8%) were infected with strains belonging to group G2, and 15 patients (21.9%)
      were infected with strains belonging to group G3. This result indicated that
      UL144 group G1 was the predominant genotype in congenital and/or perinatal HCMV
      infection in northern China. Compared with the distribution pattern of strains in
      UL144 genotypes of data from Chicago, Iowa and Texas, and Japan by chi-square
      test, the difference was statistically significant. This suggested that the
      distribution pattern of strains in UL144 genotype was related to geographic
      location. However, no linkage was observed between the UL144 genotypes and the
      severity and/or outcome of HCMV disease.

PMID- 16896553
TI  - Grayscale calibration and quality assurance of diagnostic monitors in a PACS
      system.
AB  - PURPOSE: The aim of this study was to calibrate monitors used in soft-copy review
      of diagnostic images in a pictures archiving and communication system (PACS) and
      to assess critical quality assurance (QA) parameters through appropriate checks.
      MATERIALS AND METHODS: Barco [cathode ray tube (CRT) and liquid crystal display
      (LCD)] and EIZO (LCD) monitors were evaluated. Calibration and QA controls were
      carried out during acceptance tests on the systems and every 6 months according
      to the Task Group 18 (TG18) report by the American Association of Physicists in
      Medicine (AAPM). The parameters in question include: maximum luminance, contrast
      ratio, luminance response, spatial resolution and angular response. A subjective
      evaluation of image quality was also conducted by a number of radiologists.
      RESULTS: Barco medical monitors' results were well within tolerances, with
      significant parameters persisting over time. EIZO nonmedical monitors showed
      rapid performance deterioration below the minimum requirements. Calibration had
      to be repeated only in a few cases. Radiologists' evaluations showed that monitor
      quality is equal to or even better than that of conventional films. CONCLUSIONS:
      Medical monitors turned out to be fully adequate to the task. Periodic QA tests
      are, however, absolutely necessary to ensure constant quality levels.

PMID- 16896554
TI  - Cowper's glands and ducts: radiological findings in children.
AB  - PURPOSE: The aim of this study was to describe the radiological features of
      simple or dilated (syringocele) Cowper's ducts in a large paediatric population.
      MATERIALS AND METHODS: Voiding cystourethrography procedures performed during the
      past 24 years were evaluated taking into special account urethral morphology. The
      procedures were performed to study all sorts of possible urinary affections.
      RESULTS: A total of 1,676 male children (age: newborn to 18 years) underwent
      2,340 voiding cystourethrographies. Opacification of Cowper's ducts was observed
      in nine children (0.53%) - in six (0.35%) as a thin, radiopaque image running
      parallel to the inferior edge of the membranous-bulbar urethra and in three
      (0.18%) as a dilated structure (syringocele); this was a source of significant
      voiding problems. CONCLUSIONS: Opacification of Cowper's ducts - even if rare -
      has to be recognised as a possible anatomical finding during voiding
      cystourethrography in paediatric patients. An accessory finding devoid of
      pathological meaning in most cases, it can, however, be a possible cause of
      voiding disorders in some instances.

PMID- 16896555
TI  - Ultrasonographic analysis in vitro of parietal thickness of lower limb varicose
      veins.
AB  - PURPOSE: The aim of this study was to evaluate the ability of ultrasound (US) to
      measure the parietal thickness of varicose veins. MATERIALS AND METHODS: In a
      blind in vitro analysis, 28 great saphenous veins, obtained after stripping
      surgery from 28 patients with chronic venous insufficiency, were examined with a
      digital US scanner ATL-HDI5000, linear 5-1 to 2-MHz broadband probe, compound
      imaging technique and analogic-digital zooming. We obtained one to three
      progressive measurements for each vein wall (total 67 parietal thicknesses). The
      samples, fixed in formalin, were sent to the pathology laboratory: sections were
      obtained at the same level of the sonographic planes, and images were obtained by
      digital camera mounted on an optical microscope. Measurements obtained at
      histology were considered as the gold standard. K-statistic was applied to
      compare sonographic and histologic measurements. RESULTS: Considering only the
      hypoechoic wall portion, 29/29 (100%) diagnoses of hypotrophy (K=0.91), 19/22
      (86%) diagnoses of normotrophy (K=0,47) and 12/16 (75%) diagnoses of hypertrophy
      (K=0.7) were obtained by sonography. CONCLUSIONS: In our preliminary experience,
      the in vitro study of varicose veins allows precise, at least morphological,
      detection of hypotrophic walls. If these preliminary data are confirmed in vivo,
      sonography could be used to discriminate patients eligible for conservative
      treatment instead of surgery.

PMID- 16896556
TI  - MDCT assessment of lung volume in patients undergoing bronchial stenting for
      treatment of pulmonary emphysema: correlation with respiratory tests and personal
      experience.
AB  - PURPOSE: The aid of this study was to evaluate lung volume reduction with
      multidetector-row computed tomography (MDCT) in patients with emphysema who have
      undergone endobronchial valve placement. MATERIALS AND METHODS: Nine patients
      with emphysema were studied by low-dose chest MDCT (64-slice Somatom Sensation
      Cardiac, Siemens) with a collimation of 64 x 0.6 mm and a slice thickness of 1
      mm. After treatment, MDCT scans were repeated at 7 and 30 days. A single observer
      calculated the volume of the treated lobe and of both lungs on a dedicated
      console. Volume calculations were then compared with the results of lung function
      tests. RESULTS: Four patients in whom MDCT showed severe emphysema of the right
      upper lobe (RUL) were selected for endobronchial valve insertion. Volume
      assessment at 30 days showed a 29% reduction in RUL volume in patient A, a 15%
      reduction in patient B, a <1% reduction in patient C and a 30% reduction in
      patient D. Correlation with lung function tests confirmed a major reduction of
      forced expiratory volume in 1 s (FEV(1)) and vital capacity (VC) and improved
      walking test results after 7 and 30 days. CONCLUSIONS: In patients undergoing
      endobronchial valve placement, MDCT with dedicated software allows for a better
      evaluation of volume reduction of a single lobe and of the whole lung.

PMID- 16896557
TI  - Ultrasound and magnetic resonance imaging in sports-related muscle injuries.
AB  - PURPOSE: The objective of this study was to evaluate the role of magnetic
      resonance imaging (MRI) and ultrasonography (US) in the diagnosis of traumatic
      muscle injuries. MATERIALS AND METHODS: From June 2003 to June 2004, 81 football
      players with a history of traumatic muscle injuries to the lower limbs were
      examined. US was performed shortly after the trauma (from 6 to 72 h afterwards)
      and MRI within a maximum of 5 days. RESULTS: MRI revealed 26 minor and 55 major
      traumas. MRI and US showed complete concordance in 71 patients (site, type and
      extent of injury). US produced ten false negative results, including six minor
      lesions and four major lesions. US had a sensitivity of 87.65% in the correct
      identification of muscle injuries; its sensitivity was 92.72% for major lesions
      and 76.92% for minor lesions, 57% for delayed-onset muscle soreness (DOMS), 80%
      for lengthenings, 83% for contractures, 84% for strains, 87.5% for mild
      contusions and 100% for severe contusions. CONCLUSIONS: US is the first-line
      technique for examination of muscle injuries. MRI is able to reveal lesions that
      may be missed at US and provide a more accurate assessment of site and extent of
      injury.

PMID- 16896558
TI  - Magnetic resonance imaging of posterior cruciate ligament injuries: a new
      classification of traumatic tears.
AB  - PURPOSE: The aim of our study was to propose a new classification of acute
      posterior ligament (PCL) injuries based on magnetic resonance imaging (MRI).
      MATERIALS AND METHODS: Using MRI, we reviewed 220 patients presenting an acute
      posterior ligament injury. The MRI exam was performed on a 0.2-Tesla (T) magnet
      and a 1.5-T magnet using T1-weighted spin echo (SE), T2-weighted SE and fat
      suppression scans [short-tau inversion recovery (STIR)] in axial, sagittal and
      coronal planes. In no case was paramagnetic contrast agent injected. RESULTS:
      Twenty-five per cent of patients were identified as having type I lesions and
      another 30% as having type II lesions according to the Gross classification. Out
      of 77 patients, 35% of the whole sample, 37 had a tear of the posteromedial
      fascicle (type II lesion), and the remaining 40 had anterolateral fascicle tears
      (type III). In 10% of cases, the ligaments appeared completely interrupted, and
      these were classified as type IV lesions. CONCLUSIONS: T1-weighted SE sequences
      need to be integrated with T2-weighted and STIR sequences to detect the real
      extent of the remaining fascicle. The MRI exam could thus be able to provide a
      qualitative evaluation of PCL injuries and establish how the injury compromises
      joint stability.

PMID- 16896559
TI  - Role of videofluorography swallow study in management of dysphagia in
      neurologically compromised patients.
AB  - PURPOSE: The aim of this study was to demonstrate the key role of the
      videofluorography swallow study (VFSS) in the management of patients with
      dysphagia and varying degrees of neurological deficit. MATERIALS AND METHODS: In
      1 year (March 2004-March 2005) 47 patients with oropharyngeal dysphagia due to
      different types of neurological deficit and who required rehabilitation were
      studied. All patients underwent: (1) clinical history assessment, (2) speech
      therapy assessment and (3) VFSS using digital fluoroscopy (25 frames per second).
      Patients were divided according to the Waxman classification into seven levels of
      dysphagia, and the most suitable type of feeding was selected (normal diet,
      restricted diet, artificial nutrition). At discharge, the possibility of changing
      the dietary regimen followed in hospital was evaluated based on clinical
      progress, radiological follow-up and the degree of improvement obtained. RESULTS:
      VFSS confirmed aspiration in 21/47 (44%) patients, of whom four (8%) had not been
      suspected at clinical-speech therapy assessment. In 13/47 (28%) patients, VFSS
      identified changes at the oral (three patients) or pharyngeal stage (three
      patients) or both (seven patients) but with no signs of silent aspiration. In the
      remaining 13 (28%) patients, VFSS did not show any changes in swallow dynamics.
      On the basis of these data, together with the follow-up at the end of
      rehabilitation treatment, different nutritional strategies were adopted:
      artificial nutrition [percutaneous endoscopic gastrostomy (PEG) or nasogastric
      tube], a restricted-consistency diet or normal diet. CONCLUSIONS: Our experience
      shows that VFSS precisely classifies the degree of dysphagia that conditions the
      dietary management of each neurologically compromised patient.

PMID- 16896560
TI  - Multimodal imaging of esophagus and cardia cancer before and after treatment.
AB  - PURPOSE: Prognosis and treatment of esophagus and cardia cancer (ECC) depend on
      the precision with which the disease is staged according to the American Joint
      Committee of Cancer (AJCC) criteria. Imaging modalities normally used in clinical
      staging are esophagography, esophagoscopy, endoscopic ultrasound (EUS), computed
      tomography (CT) and positron emission tomography- CT fusion (CT-PET). The
      combination of these methods is crucial in determining not only the right
      diagnosis but also the stage and follow-up after multimodal treatment. The
      purpose of our investigation was to define the role of each imaging modality in
      determining the most appropriate treatment options in patients with ECC.
      MATERIALS AND METHODS: Fifty-six patients with ECC diagnosed by X-ray of the
      upper digestive tract, endoscopy and biopsy were staged using EUS, chest and
      abdomen CT scan, and CT-PET. Thirty-four patients in stage II and 18 patients in
      stage III underwent surgery after neoadjuvant chemotherapy; four patients in
      stage IV were treated with the positioning of an endoprosthesis after
      chemoradiotherapy. In the 52 patients who had surgery, follow-up included
      digestive tract X-ray, endoscopy and CT of the chest and abdomen every 6-8 months
      for the first 3 years. CT-PET was only performed in patients with a clinical
      suspicion of recurrence and/or CT findings suspicious of persistent disease (12
      cases). RESULTS: In all 56 patients, endoscopy, EUS, CT and CT-PET in combination
      were crucial in determining the site of disease, locoregional extent and depth of
      esophageal wall penetration (T), and any involvement of the mediastinal lymph
      nodes (N1), extrathoracic lymph nodes (M1) or hepatic metastases. In the
      locoregional staging of ECC before chemotherapy, we were able to differentiate T2
      T3 from T4 in 40 patients; T4 disease was found in 12 potentially resectable
      cases. We were able to distinguish N0 from N1 in 12 patients. In four cases, the
      presence of small lymph node and/or liver metastases prompted positioning of an
      endoprosthesis. The specificity of CT in detecting small lymph nodes in the
      mediastinum was less than 50% while for CT-PET, it was more than 80%; EUS
      revealed sensitivity higher than 90% but a low specificity in seven cases. Only
      CT-PET revealed metastatic subdiaphragmatic lymph nodes (diameter <15 mm) in
      three cases. Presurgical restaging of the 18 patients (stage III) who had
      chemotherapy was based on endoscopy, EUS, CT of the chest and abdomen and CT-PET
      (only in suspected cases) and was compatible with surgery. Anastomotic recurrence
      was diagnosed in 16 patients by endoscopy with associated biopsy; any
      intramediastinal spread from anastomotic recurrences was evaluated by chest CT,
      and CT-PET in suspected cases. CONCLUSIONS: X-ray of the upper digestive tract
      and chest and abdomen CT scan are useful in preliminary evaluation of ECC.
      Endoscopy is particularly indicated for evaluating tumour morphology, taking
      biopsies for a histological diagnosis and the early diagnosis of anastomotic
      recurrences. EUS is indicated mainly for evaluating T stage before and after
      chemotherapy or chemoradiotherapy. CT-PET is extremely useful in identifying
      small mediastinal metastatic lymph nodes (N1) or extrathoracic lymph nodes (M1)
      and hepatic metastases (</=1 cm), which may escape multislice CT. PET alone is
      useful for identifying residual or recurrent tumour in the esophageal wall when
      an endoprosthesis is in place.

PMID- 16896561
TI  - Analysis of the results of a proficiency test in screening mammography at the
      CSPO of Florence: review of 705 tests.
AB  - PURPOSE: The aim of this study was to evaluate the performance of a sample of
      Italian radiologists undergoing a proficiency test of screening mammography.
      MATERIALS AND METHODS: We retrospectively analysed the results of 705 tests (537
      first tests, 168 repeat tests) taken during 1997-2005 by 537 Italian
      radiologists. The test, consisting of 17 screen-detected cancer cases and 133
      negative controls, was validated by a panel of expert readers defining a minimum
      standard as to sensitivity for cancer and recall rate of negative controls.
      Success rates were assessed as a function of previous experience in mammography
      (years of experience, total mammograms read, mammograms read in the last year).
      RESULTS: A total of 176 radiologists successfully passed the test at their first
      attempt (32.7%). Success correlated with experience, measured in terms of years
      of experience (5-year cutoff: chi(2) for trend=4.17, p=0.04), total mammograms
      read (chi(2) for trend =11.8, p=0.002) or mammograms read in the last year
      (chi(2) for trend=6.27, p=0.04). Training improves performance at repeat testing:
      after a first negative attempt, a second attempt was successful in 50.6% of cases
      (74/146) and a third in 68.1% (15/22). CONCLUSIONS: A substantial proportion of
      Italian radiologists taking the test showed limited proficiency in screening
      mammography. This finding is consistent with several reports of poor performance
      of service screening compared with reference standards. As expected, test
      performance is associated with experience, suggesting that the current policy of
      employing non-dedicated, untrained, general radiologists in screening should be
      reconsidered. Test performance improves with training (courses, consultation of
      teaching atlases). Several screening programmes in Italy have been implemented
      without prior adequate radiologist training. Radiologist training needs to be
      considered a priority, at least in those screening programmes that are still to
      be implemented in one third of the country.

PMID- 16896562
TI  - Sonographic criteria for differentiation of benign and malignant solid breast
      lesions: size is of value.
AB  - PURPOSE: The purpose of this study was to evaluate whether lesion size may
      influence the value of sonographic findings in the differential diagnosis between
      benign or malignant breast lesions. MATERIALS AND METHODS: Sonographic features
      of 256 histologically confirmed (148 benign, 108 malignant) breast lesions were
      retrospectively and independently reviewed by three radiologists unaware of
      mammographic findings and pathology results. Each lesion was assessed for several
      sonographic features and assigned a level of suspicion. Logistic modelling
      defined the predictive value of each sonographic feature per se and in relation
      to lesion size. The k statistic (k) evaluated interobserver agreement in lesion
      classification. The accuracy of breast sonography in characterising solid lesions
      was also evaluated. RESULTS: Analysis of the sonographic features predictive of
      malignant disease, taken as a whole, showed that only irregular margins and
      marked hypoechogenicity maintain their predictive value independent of lesion
      size. When lesion size is considered, the other features remain significant only
      for lesions larger than 7 mm. Interobserver agreement for sonographic suspicion,
      when calculated not taking into account lesion size, was good or excellent
      whereas it was reduced for lesions smaller than 7 mm. Accuracy of breast
      sonography improved when evaluating lesions larger than 7 mm. CONCLUSIONS: Lesion
      size influences the value of sonographic findings in distinguishing benign from
      malignant lesions. The usually adopted criteria in sonography have a
      significantly lower accuracy in characterisation of small lesions.

PMID- 16896563
TI  - Tubular carcinoma of the breast: pathological, clinical, and ultrasonographic
      findings. A review of the literature.
AB  - PURPOSE: Tubular carcinoma of the breast is a well-differentiated adenocarcinoma.
      The aim of this paper is to analyse its clinical and imaging findings and to
      review the radiological literature. MATERIALS AND METHODS: A retrospective review
      of 560 consecutive histologically proven carcinomas of the breast was made.
      RESULTS: Sixteen pure (tubular component >90%) tubular carcinomas were found in
      14 women (mean age 55 years). Three lesions were palpable. At mammography, five
      were not detected, three presented as spiculated masses, two as masses with
      irregular margins, two as spiculated masses with microcalcifications, two as
      distortions, one as a cluster of microcalcifications and one as asymmetric
      density. At ultrasonography, two lesions were not detected; the remaining
      presenting as hypoechoic nodules with irregular (13) or well-defined (one)
      contours. Fine-needle aspiration cytology diagnosed 11 carcinomas and two
      "atypical cells". In three, core biopsy was made: in the first, a complex
      sclerosing lesion with atypical cells was suggested, in the second differential
      diagnosis between tubular carcinoma and sclerosing adenosis was proposed and in
      the third a tubular carcinoma. The mean diameter of the lesions at histopathology
      was 9.7+/-4.9 mm. Metastatic nodes were found in one patient only. CONCLUSIONS:
      Tubular carcinoma presents as a small, nonpalpable lesion, with nonspecific
      imaging patterns. Nodal metastases are rare.

PMID- 16896564
TI  - Follow-up of mediastinal lymphoma: role of ultrasonography.
AB  - PURPOSE: Patients with lymphoma are often young and require long and intensive
      treatment, the toxic effects of which compound the impact of frequent
      radiological examinations. Computed tomography (CT) is of great value in the
      evaluation of the mediastinum, which is frequently involved by the disease, but
      carries a high radiation load. Ultrasonography (US) has therefore been proposed
      as an alternative procedure to evaluate response to treatment. Major advantages
      include good compliance, absence of patient risks, low cost, easy
      reproducibility, dynamic images enabling multiplanar evaluation and qualitative
      and quantitative criteria. The purpose of this study was to investigate the role
      of US in evaluating response to treatment in patients with mediastinal lymphomas
      using CT as the gold standard. MATERIALS AND METHODS: In 2005, 12 patients were
      evaluated by chest X-ray, mediastinal sonography and contrast-enhanced CT (gold
      standard). Each mediastinal region was accurately assessed for adenopathies.
      Lymph nodes were studied by evaluating their structure and morphology, measuring
      their size and classifying them according to location. RESULTS: US proved to be
      more sensitive and accurate (93%) than X-ray [66% sensitivity and 68% diagnostic
      accuracy (DA)]. In particular, the best sensitivity values were observed in the
      supraaortic (97% vs. 55%), prevascular (97% vs. 39%) and paratracheal (87% vs.
      77%) regions and in the aortopulmonary window (80% vs. 0%). Deeper mediastinal
      compartments (subcarinal region and posterior mediastinum) could not be assessed.
      X-ray proved to be superior in hilar adenopathies only. US provides qualitative
      information (hypoechoic or hyperechoic tissues) in addition to quantitative data
      (maximum diameter of each lymph node) it shares with CT. DISCUSSION.: Compared
      with X-ray, US allows for a better evaluation of the anterior mediastinal
      regions, showing small, central adenopathies that do not alter the mediastinal
      lines on X-ray. It is, however, of very limited value in the evaluation of
      posterior compartments because of their deep location. US adds qualitative
      criteria to the quantitative criteria typical of CT. Limitations of mediastinal
      US include site of adenopathies, dependence on the patient's characteristics
      (body habit, concurrent diseases and chest anatomy) and dependence on the
      operator. CONCLUSIONS: US may have a specific role in monitoring patients with
      mediastinal adenopathies, providing early indications on possible response to
      treatment and allowing the frequency of CT follow-up scans to be reduced. In
      conclusion, US may be used to complement, but not replace CT, which remains the
      gold standard.

PMID- 16896565
TI  - An inconstant ligament in the popliteal region associated to the superior
      genicular arteries: surgical importance.
AB  - MATERIALS AND METHODS: In the dissection of 60 knees of 30 cadavers (13 women and
      17 men), a ligament was located in the posterior femur face above the lateral or
      medial condyle. RESULTS: This ligamentous structure was found in 12 (20%) out of
      60 knees studied (38% of the women and 35% of the men). It had a vertical
      arrangement and a constant direct relation to the superior (lateral or medial)
      genicular artery, and in no case it appeared as a posterior reinforcement of the
      capsule. The superior vessels were fixed by this ligament. DISCUSSION: This
      fixation may provide stability to the vascular tree but it could be a cause of
      post-surgical hemarthrosis in arthroscopy of the posterior knee area or in
      posterior or lateral knee approaches or it could be even implicated in vascular
      injury of the popliteal artery during knee dislocation. CONCLUSION: The objective
      was to describe this inconstant ligament and to study its clinical relevance for
      surgical procedures, and particularly for those using the posterior approach to
      the knee joint.

PMID- 16896566
TI  - Shear mechanical anisotropy of side chain liquid-crystal elastomers: influence of
      sample preparation.
AB  - We study the mechanical anisotropy of a series of uniaxial side chain nematic
      elastomers prepared with the same chemical composition but with different
      preparation protocols. For all the compounds, the experiments performed as a
      function of temperature show no discontinuity in both G' (//) and G' (
      perpendicular) (the labels // and perpendicular stand for the director parallel,
      respectively perpendicular to the shear displacement) around the nematic
      isotropic (N-I) phase transition temperature determined by DSC. They also all
      show a small decrease in G' (//) starting at temperatures well above this
      temperature (from approximately 4( degrees ) C to approximately 20( degrees ) C
      depending on the compound studied) and leading to a small hydrodynamic value of
      the G' ( perpendicular)/G' (//) ratio. The measurements taken as a function of
      frequency show that the second plateau in G' (//) and the associated dip in G
      (//)" expected from dynamic semi-soft elasticity are not observed. These results
      can be described by the de Gennes model, which predicts small elastic anisotropy
      in the hydrodynamic and linear regimes. They correspond to the behavior expected
      for compounds beyond the mechanical critical point, which is consistent with the
      NMR and specific heat measurements taken on similar compounds. We also show that
      a reduction in the cross-linking density does not change the non-soft character
      of the mechanical response. From the measurements taken as a function of
      frequency at several temperatures we deduce that the time-temperature
      superposition method does not apply. From these measurements, we also determine
      the temperature dependence of the longest relaxation time tau(E) of the network
      for the situations where the director is either parallel or perpendicular to the
      shear velocity. Finally, we discuss the influence on the measurements of the
      mechanical constraint associated with the fact that the samples cannot change
      their shape around the pseudo phase transition, because of their strong adherence
      on the sample-bearing glass slides.

PMID- 16896567
TI  - [Candidate genes and polymorphism analysis in type 2 diabetes mellitus].
AB  - BACKGROUND AND PURPOSE: Diabetes mellitus type 2 is a polygenic disease. Up to
      now, numerous candidate genes have been examined and tested for their association
      to metabolic parameters and late complications of diabetes. Between 2000 to 2004,
      polymorphisms of the following genes and their association to metabolic
      parameters and late complications of diabetes were examined in the authors'
      laboratory: PAI-1 (plasminogen activator inhibitor-1), PPARgamma2 (peroxisome
      proliferator-activated receptor gamma2), UCP-1 (uncoupling protein-1), and
      adiponectin. Based on this, the question was examined whether the combination of
      the respective rarely occurring genotypes results in an increased atherogenic
      risk and a higher prevalence of micro- and macrovascular late complications of
      diabetes. MATERIAL AND METHODS: Subjects were enrolled from a cohort of 570 type
      2 diabetic patients (246 female and 324 male, mean age 66.9+/-9.2 years) who had
      participated in a population-based study on diabetes and its complications in a
      mobile survey unit in 23 towns and villages in Bavaria (Germany). Retinopathy was
      diagnosed by nonmydriatic fundus photography (Canon CR4-45 NM). Photographs of
      the retina of both eyes (one photo per eye) were taken. Data on macrovascular
      complications of diabetes were obtained using a standardized questionnaire.
      RESULTS: A significant association between the number of rarely occurring
      genotype combinations and the following parameters could be described: diastolic
      blood pressure, total cholesterol, HDL cholesterol, LDL cholesterol,
      triglycerides, and grade of retinopathy. CONCLUSION: An accumulation of certain
      genotypes of candidate genes for diabetes mellitus type 2 is associated with the
      severity of dyslipidemia and microvascular late complications, e.g., grade of
      retinopathy. Therefore, screening for genotype combinations of these metabolic
      target genes might offer the opportunity to identify diabetic patients at a high
      risk for macro- and microvascular complications.

PMID- 16896568
TI  - [Requirements for the development of molecularly defined targeted therapy in
      oncology].
AB  - BACKGROUND: The revolutionary development in the biosciences during the last 15
      years--including the sequencing of the human genome and multiple other genomes as
      well the possibility of massive parallel analysis of thousands of data points
      within a single experiment--have greatly improved our understanding of the
      pathophysiology of tumor development and progression as well as metastasis. THE
      CURRENT SITUATION: The further development of genomic technology for routine
      clinical use is slowly but steadily leading to a paradigm shift: the currently
      used tumor definition based on pathologic and histological assessment is replaced
      by molecularly defined tumor subtypes. This is an essential prerequisite for the
      development of molecularly defined individualized therapies in oncology leading
      to more effective treatments with less severe side effects. The first molecularly
      defined drugs (targeted drugs) have already entered the clinical arena. However,
      not only diagnostics and therapy on oncology will change dramatically in the
      future, but also the way we have to organize oncology itself. OUTLOOK: The
      integration of genomics and information technologies will require the
      establishment of interdisciplinary teams beyond the already established
      collaborations between surgeons, radiotherapists and medical oncologists.

PMID- 16896569
TI  - [Primary thrombocythemia: diagnosis and therapy].
AB  - BACKGROUND: Primary thrombocythemia is a rare acquired chronic disorder of the
      bone marrow which can occur at any age. Diagnosis is based upon elevated platelet
      counts, morphologically and functionally altered platelets and characteristic
      bone marrow alterations as well as the exclusion of related myeloproliferative
      disorders which can also be accompanied by increased platelet counts. Possible
      disease complications are thromboembolic and hemorrhagic events as well as a
      transformation into myelofibrosis or acute leukemia. Inhibition of platelet
      aggregation with aspirin for the prevention of thromboembolic complications is
      first-line therapy; cytoreductive therapy with drugs such as hydroxyurea or
      interferon-alpha or thromboreductive therapy with the platelet-reducing agent
      anagrelide is required when thromboembolic complications are already present at
      diagnosis (secondary prevention) or when platelet counts are steadily increasing
      or various additional risk factors are present (primary prevention). Because of
      the potential adverse effects of the various therapies upon long-term application
      a strict risk-benefit analysis is mandatory before initiation of therapy. In up
      to 50% of the patients the recently discovered V617F mutation in the JAK2 gene
      can be identified which is supposed to be involved in the pathogenesis of this
      disease. CLINICAL STUDIES: Because of the rarity of primary thrombocythemia thus
      far only two prospectively randomized studies have been carried out to compare
      cyto- and thromboreductive therapies. In the British PT1 study the mandatory
      combination of anagrelide with aspirin was compared with the combination of
      hydroxyurea and aspirin, in the European ANAHYDRET study monotherapy with
      hydroxyurea was compared with that of anagrelide. This different study design has
      caused an intense controversy about the results of these studies obtained thus
      far. CONCLUSION: Due to the existence of randomized clinical studies expert
      opinion will, in the future, be increasingly replaced by evidence-based therapy
      guidelines. The improved knowledge of the molecular basis of the disease because
      of the discovery of the V617F mutation in the JAK2 gene has improved the
      molecular diagnosis and opened new avenues to molecular-targeted therapies.

PMID- 16896570
TI  - [Prevalence, drug treatment and metabolic control of diabetes mellitus in primary
      care].
AB  - BACKGROUND AND PURPOSE: The primary care sector is of key importance for the
      management of patients with diabetes mellitus. The authors investigated (a) the
      prevalence of diabetes mellitus type 1 and type 2, (b) the type and frequency of
      non-drug and drug treatment and its association with the presence of diabetic
      complications, and (c) the quality of metabolic control by HbA1c. METHODS: Using
      a nationwide probability sample of 3,188 general practices (response rate [RR]
      50.6%), a total of 55,518 (RR 93.5%) patients were assessed in a prospective
      cross-sectional study by their physicians in September 2003 in a standardized
      manner using questionnaires, physician interview, and laboratory assessments. In
      addition to diabetes mellitus, 28 diseases were explicitly screened for, among
      them typical macrovascular (coronary heart disease, cerebrovascular disease,
      peripheral arterial disease) and microvascular disease (neuropathy, nephropathy,
      retinopathy, diabetic foot) complications. RESULTS: The prevalence of diabetes
      mellitus was 0.5% (type 1) and 14.7% (type 2), respectively. 49.5% (type 1) and
      50.2% (type 2) of patients had micro- or macrovascular complications. 6.8% did
      not receive any treatment, 13.5% received non-drug treatment, and 75.3% received
      oral antidiabetic drugs and/or insulin (26.6% a combination of two or more).
      Compared to diabetics without any complications, treatment intensity was
      significantly higher in patients with microvascular complications (odds ratio
      [OR] 3.02), but not in those with macrovascular complications only (OR 0.98). An
      HbA1c value>or=7.0% was recorded in 39.6% of patients. CONCLUSION: Compared to
      previous studies in this setting, the proportion of diabetics with drug treatment
      has increased. More patients receive antidiabetic drug combinations. Quality of
      blood sugar control appears to have improved as well.

PMID- 16896571
TI  - [Current thyroid diagnostics and therapy in disorders of fertility and in
      pregnancy].

PMID- 16896572
TI  - [Combined-heterozygous deficiency of complement C7 in a patient with recurrent
      meningitis].
AB  - BACKGROUND: The association between complement deficiencies and the increased
      risk for meningococcal infections and bacterial meningitis is well described and
      most striking in patients with deficiencies of one of the late complement
      components, i.e., C5-C9. CASE REPORT: In the presented study the first case of a
      patient with combined-heterozygous deficiency of complement C7 is described. The
      defect led to a strongly reduced but still measurable production of C7. However,
      the low concentration of C7 was not protective against recurrent bacterial
      meningitis. CONCLUSION: The reported case illustrates once again the necessity of
      complement analysis in patients with meningitis. Not only patients with
      undetectable complement activity but also those with strongly reduced but still
      measurable complement function should be analyzed for a possible complement
      deficiency.

PMID- 16896573
TI  - [Cerebral vein thrombosis as a complication of a florid ulcerative colitis].
AB  - BACKGROUND: Thromboembolic episode, especially cerebral vein thrombosis, is a
      rare extraintestinal complication of ulcerative colitis. In world literature less
      than 100 cases are reported. Although the existence of coagulation alterations
      and fibrinolysis have been suggested, the exact mechanism of hypercoagulability
      in patients with ulcerative colitis is still unknown. CASE REPORT: The authors
      report of a 35-year-old female patient with ulcerative colitis, that has existed
      for several years. She developed strong cephalgias without further neurologic
      symptoms in an acute attack of her disease. Magnetic resonance imaging led to the
      diagnosis of an extensive acute cerebral vein thrombosis. Other possible reasons
      for a coagulopathy were excluded. CONCLUSION: Cerebral vein thrombosis is a rare,
      but severe complication of ulcerative colitis. Thus, the presence of neurologic
      symptoms in a patient with known ulcerative colitis should lead to immediate
      diagnosis and treatment.

PMID- 16896574
TI  - [German Competence Network on Atrial Fibrillation (AFNET). A nationwide
      cooperation for better research and patient care].
AB  - The Atrial Fibrillation Competence Network is an interdisciplinary national
      research network funded by the Federal Ministry of Education and Research (BMBF).
      The aim of the network--founded in 2003--is to improve the treatment of atrial
      fibrillation, the most common clinically important arrhythmia of the heart. A
      decentralized patient registry has been established. This registry, which
      comprises the manifestation, diagnostics and therapy of atrial fibrillation in
      Germany, is being used as a data basis for epidemiologic clinical studies.
      Epidemiologic projects are being conducted to study, e.g., the prevalence of
      atrial fibrillation as well as the occurrence of complications. Four multicenter
      clinical trials have been started to optimize pharmacological treatments (ANTIPAF
      trial, Flec-SL trial), preventive pacing (BACE-PACE trial) and catheter-based
      ablation (GAP-AF trial). Other clinical projects are being conducted to study the
      risk of neurologic complications and to develop new diagnostic imaging
      techniques. Experimental basic research projects are focusing on different
      aspects of atrial remodeling in order to find out in which way the molecular
      mechanisms can be manipulated by new methods of treatment. First results are
      presented.

PMID- 16896575
TI  - Detection of influenza transmission to healthcare workers - learning from the
      SARS "Era".

PMID- 16896576
TI  - Moxifloxacin versus standard therapy in patients with pneumonia hospitalized
      after failure of preclinical anti-infective treatment.
AB  - The failure rate of primary empirical anti-infective treatment of community
      acquired pneumonia is reported to range between 2 and 7%. These patients are
      subject to a greater risk of intensive medical treatment and a higher mortality
      rate than patients who respond to primary treatment. We investigated 63 patients
      in a "real life scenario" who were admitted to the hospital after failure of
      primary outpatient therapy for community-acquired pneumonia. Thirty-three
      patients received intravenous standard therapy (betalactam 14, macrolide 3,
      levofloxacin 6, doxycycline 1, combinations 9 patients) while 30 patients were
      treated with intravenous moxifloxacin. The oral antibiotic pretreatment that
      failed most frequently was clarithromycin (n = 25), followed by
      amoxicillin/clavulanic acid (n = 16), cefixime (n = 10), cefuroxime/axetil (n =
      5), doxycycline (3), cefpodoxime, and ciprofloxacin (2 each). There were no
      differences between the two groups in respect of age, gender, numbers of patients
      in nursing homes, numbers of patients with different underlying diseases (chronic
      bronchitis, coronary heart disease, diabetes mellitus, smoking, etc.), severity
      of pneumonia at the time of admission, numbers of patients requiring intensive
      care, and lethality. The group that underwent standard therapy experienced
      failure of the empirical intra-hospital antibiotic therapy more often during
      therapy [10 (30%) patients vs 2 (6%) in the moxifloxacin group, p = 0.009] and
      clinical failure of treatment on day 28 after initiation of therapy [7 (21%)
      patients vs 2 (6%) in the moxifloxacin group, p = 0.003]. In cases of failure of
      empirical preclinical antibiotic treatment for community-acquired pneumonia,
      subsequent intrahospital treatment with moxifloxacin is more successful than
      standard therapy in our study reflecting a "real life scenario".

PMID- 16896578
TI  - Difference of HBV genotype distribution between acute hepatitis and chronic
      hepatitis in Japan.
AB  - BACKGROUND: Recently genotype A which is rare in the patients in chronic
      hepatitis B (CHB) was frequently noted in patients with acute hepatitis B (AHB).
      To investigate their clinical and virological features, we studied the AHB
      patients in the past 5 years. PATIENTS AND METHODS: 98 patients with AHB and 80
      patients with CHB admitted to our hospital between 1998 and 2003 were studied.
      RESULTS: Genotype A was not found in CHB but was frequently noted in AHB (p <
      0.001). Comparison of the clinical features of acute hepatitis between the two
      major genotypes, A and C, homosexual and heterosexual with multiple partners were
      frequently seen among genotype A patients (p < 0.001). On the other hand,
      infection from steady partner showed a tendency to be more frequent in genotype C
      (p = 0.065). In genotype A, the levels of HBVDNA on admission was higher (p =
      0.007) and AHB has significantly more frequently progress to chronic infection
      than in genotype C (p = 0.028). Phylogenetic analysis of genotype A revealed that
      almost all strains from homosexual men belonged not to the African type A1 but to
      the Western type A2. CONCLUSION: Genotype A has increased recently among AHB in
      Japan. This fact may correlate to promiscuous intercourse in high risk group.
      Prophylactic efforts should be considered to prevent the prevailing of genotype
      A.

PMID- 16896577
TI  - Opportunistic infections and other AIDS-defining illnesses in Poland in 2000
      2002.
AB  - BACKGROUND: The introduction of highly active antiretroviral therapy (HAART) led
      to a decreased incidence of the most severe opportunistic infections (OIs) in HIV
      infected patients. In Poland, HAART became widely used in 1998. MATERIALS AND
      METHODS: This study was based on data from medical records data collected in the
      years 2000-2002 from medical centers for HIV-infected patients in Poland. The aim
      of the study was to determine the incidence of opportunistic infections (OIs) and
      other AIDS defining illnesses (ADIs). The chi(2) test was used to determine any
      significant trends. RESULTS: The incidence of ADIs was 6.8, 6.5 and 4.8/100
      persons/year in 2000-2002, respectively. The most common diagnosed OIs were:
      fungal infections, tuberculosis, recurrent pneumonia, PCP and toxoplasmosis. In
      patients receiving HAART (HAART+) the incidence of ADIs was significantly lower
      than in non-ARV-treated as well as in all HIV+ (p < 0.02, p < 0.001, p < 0.001,
      respectively). A significant decrease in the incidence of ADIs in HAART+ patients
      between 2000 and 2002 (p < 0.0001) was observed. From 25% to 30% of ADIs among
      HAART+ patients were diagnosed within the first 3 months of antiretroviral
      therapy. In HAART+ patients the most common ADIs were fungal infections and
      tuberculosis. The diagnosis of ADIs resulted in the recognition of HIV status in
      8.7-8.9% of patients. CONCLUSIONS: Five years after the introduction of HAART the
      incidence of ADIs had declined. Fungal infections and tuberculosis were the most
      common OIs in HIV+ patients in Poland.

PMID- 16896579
TI  - Seroepidemiology of Varicella zoster in Israel prior to large-scale use of
      varicella vaccines.
AB  - OBJECTIVES: This large-scale study provides up-to-date estimates of Varicella
      zoster virus (VZV) age-specific seroprevalence and characteristics of VZV
      transmission in a representative sample of the Israeli population. METHODS: In
      2000-2001, 1,642 sera collected from an agestratified general population sample
      were tested for VZV antibodies using an indirect IgG ELISA system. RESULTS: The
      age-weighted VZV overall estimate was 90.2%. Seropositivity increased rapidly
      with age, from 68.9% at age 4 to 94.4% at age 7 and 96.6% at age 12 years. The
      highest force of infection was in the 4-5 years age group (0.548 per susceptible
      year) followed by the 6-9 years age group. Multivariate analysis revealed that
      VZV seroprevalence estimates were significantly associated with age and place of
      origin. The highest seroprevalence estimate was found among subjects of Eastern
      origin. CONCLUSIONS: The seroepidemiology of VZV in Israel shows a pattern
      corresponding to that described for developed European countries. This study
      indicates that the highest force of infection is in pre-school children.
      Knowledge of pre-vaccination seroepidemiology is important to evaluate the effect
      of vaccination programs on the epidemiology of the disease.

PMID- 16896581
TI  - Clustered cases of pneumonia among healthcare workers over a 1-year period in
      three Italian hospitals: applying the WHO SARS alert.
AB  - BACKGROUND: The World Health Organization (WHO) has recommended that a severe
      acute respiratory syndrome (SARS) alert should be raised when two or more
      healthcare workers (HCW) in the same health care unit fulfil the SARS clinical
      criteria, with onset of illness in the same 10-day period. However, in a number
      of European countries (including Italy) data on reasons for sickness absence are
      not routinely collected within current HCW worker sickness reporting systems,
      because of concerns about privacy. To help plan for the implementation of the
      proposed alert system in Italy, we aimed to determine the minimum number of alert
      cases defining a cluster. PATIENTS AND METHODS: Sickness absences longer than 7
      days in HCW employed in three hospitals in 2003, were identified by checking the
      hospitals' administrative databases. HCW with onset of illness in the same 10-day
      period were contacted and asked whether they have been diagnosed with pneumonia.
      RESULTS: Overall, 273 absences > 7 days were recorded and 36 clusters of at least
      two absences > 7 days were identified; a total of 94 HCW were involved in these
      clusters. Only two HCW involved in different clusters, reported pneumonia.
      CONCLUSION: The occurrence of clusters of two or more cases of pneumonia in HCW
      in the same hospital unit appears to be an uncommon event, and thus the alert
      system proposed is not likely to result in large numbers of false positive
      alerts. However, it may be difficult to implement this alert system in countries
      where clinical data on sickness absences are not routinely collected, and
      alternative mechanisms should be considered.

PMID- 16896580
TI  - Comparison in a laboratory model between the performance of a urinary closed
      system bag with double non-return valve and that of a single valve system.
AB  - BACKGROUND: Catheter-associated urinary tract infection is the most common
      nosocomial infection in clinical settings. For bacteria ascending to the bladder
      the most common route is the extraluminal, but the intraluminal route also plays
      a role. For this reason, we compared two urinary closed system bags (CSB), one
      with a double and the other with a single non-return valve (NRV), in a laboratory
      setting in order to establish their ability to prevent or delay the ascent of
      bacteria from the drainage bag to the bladder. PATIENTS AND METHODS: The tests
      were performed in two microbiological laboratories (Copenhagen (C), Denmark and
      Freiburg (F), Germany). These were blinded to each other. A urinary tract model
      using artificial urine was set up. Two sets of ten drainage bags each with a
      double NRV (CSB A), and two sets of ten drainage bags each with a single NRV (CSB
      B) were inoculated with Escherichia coli (F: ATCC 25922; C: clinical strain).
      Daily samples were taken from two drainage ports on each system - one above the
      NRV (Port I), the other above the top of the artificial bladder (Port II). Time
      till E. coli was detected at the drainage ports (time to positivity) was
      measured. Colonization of the 'bladder' was defined as time to positivity at Port
      II. RESULTS: No significant differences in time to positivity at Port I (median
      9.0, range: 6-12 for CSB B vs median 9.5 days, range: 6-13 for CSB A) were
      observed between the two systems. However, substantial differences were seen
      between the two systems in time to positivity at Port II: Port II on the bladder
      model using CSB B became positive after a median of 14.0 days (range: 10-22),
      whereas Port II of the model using CSB A only became positive after 21.5 days
      (range: 13-24). This amounts to a highly significant difference of 7.5 days (p =
      0.0001) in the mean. CONCLUSION: Under laboratory conditions, colonization of the
      'bladder' was significantly delayed when the CSB with a double NRV was used in
      comparison to the results obtained from the single NRV-system. Clinical trials
      should be conducted to investigate whether the urinary CSB with the double NRV
      has the ability to prevent (or to delay the onset of) catheter-associated urinary
      tract infection.

PMID- 16896582
TI  - Loss of varicella zoster virus antibodies despite detectable cell mediated
      immunity after vaccination.
AB  - BACKGROUND: Vaccination of children against VZV has been included in the
      recommendations of the "permanent committee of vaccination" (STIKO; Standige
      Impfkommission of the Robert Koch Institute, Berlin, Germany) in July 2004. Due
      to this recommendation the medical practitioner and the laboratories will be
      confronted with the problem of serologic non-responders or loss of humoral
      immunity more frequently. PATIENTS AND METHODS: Here we report the case of a
      Varicella Zoster Virus (VZV) vaccinee, who lost detectable VZV antibodies
      although she had a persisting VZV specific CD4 cellular immune response. We
      compare these parameters to the VZV specific CD4 T cell responses of VZV
      seronegative and seropositive healthy persons, as well as patients with VZV
      disease. RESULTS: VZV specific CD4 frequencies of VZV antibody seronegative
      persons remained on the average below 0.1% (median 0.04%, +/- SD 0.03, range 0.01
      0.08%) and were significantly lower than VZV specific frequencies of seropositive
      healthy persons (median 0.3%, +/- SD 0.24, range 0.06-0.81%; Mann-Whitney U-test
      p = 0.001). The samples of patients with VZV associated disease showed an even
      higher median level of VZV specific CD4 cell response than the VZV seropositive
      healthy persons (median 1.04%, +/- SD 1.06, range 0.51-2.92%, Mann-Whitney U-test
      p = 0.008). The VZV specific immune response of the health care worker directly
      after vaccination was comparable to the VZV specific immunity in VZV seropositive
      healthy adults. Despite serological reconversion 1.5 years later the VZV specific
      CD4 response still remained measurable and positive. CONCLUSION: The new general
      VZV vaccination recommendation for children in Germany will probably increase the
      number of persons that will be seronegative after vaccination. To gain more
      information concerning the absence of seroconversion or the loss of immunity, it
      will be necessary to focus future post-VZV vaccination immunity studies not only
      on serologic testing but also on the measuring of the cell mediated immunity.

PMID- 16896583
TI  - Isolation of toxigenic Hafnia alvei from a probable case of hemolytic uremic
      syndrome.
AB  - An 11-year-old girl presented to a central California children's hospital with a
      3-day history of erythematous lesions on her forehead, neck, and trunk, abdominal
      pain, persistent emesis, and decreased urinary output. One day prior to admission
      she had a mild bout of diarrhea with a small amount of blood in her stool. Upon
      admission her condition rapidly worsened with acute renal failure, anemia, and
      thrombocytopenia. One of the possible causes of this condition included hemolytic
      uremic syndrome. Stool cultures of this patient tested at the children's hospital
      and at a state reference laboratory were repeatedly negative for Escherichia coli
      O157:H7. However, the state reference laboratory detected a toxigenic strain of
      Hafnia alvei active on Vero cells from two consecutive stool cultures during the
      acute phase of her illness.

PMID- 16896584
TI  - Mycobacterium tuberculosis associated chylous ascites in HIV-infected patients:
      case report and review of the literature.
AB  - Chylous ascites (CA) is a rare manifestation of tuberculosis. We report a case of
      CA due to tuberculosis in an HIV-infected patient and review the literature on CA
      in HIV disease. This patient was successfully treated with large volume abdominal
      paracentesis, antituberculous drugs, and parenteral medium chain triglycerides.

PMID- 16896585
TI  - Rapid improvement of liver function in a patient with HIV and hepatitis B
      coinfection treated with lamivudine and tenofovir.
AB  - Since the introduction of HAART, the clinical importance of hepatitis virus
      infection and its complications in human immunodeficiency virus (HIV)-infected
      persons have continuously grown. Coinfection with hepatitis B virus (HBV) and HIV
      is one of the leading causes of morbidity and mortality. To date, neither the
      optimal time point for initiation of anti-HBV therapy nor the best therapeutic
      approach has been clearly defined. We report the case of a 22-year-old African
      woman infected with HBV- and HIV-1 coinfection and severe impairment of liver
      function. HAART including lamivudine and tenofovir was started. Three weeks
      later, the patient achieved not only a restoration of her clinical situation and
      liver function, but she also demonstrated a complete suppression of both viruses.
      This impressive clinical course might be explained by the application of
      antiviral combination therapy including lamivudine and tenofovir. Tenofovir has
      shown a higher activity against HBV than other drugs. In addition, combination
      therapy for chronic hepatitis B might be more effective than monotherapy. Future
      studies need to clarify the value of combination treatment for patients with
      chronic hepatitis B.

PMID- 16896586
TI  - Anicteric hepatitis in an adult associated with coxsackie b4 virus infection.

PMID- 16896587
TI  - [Whole-breast irradiation following breast-conserving surgery of ductal
      carcinomain situ is indispensable. Update of the 2005 DEGRO (German Society of
      Radiation Oncology) Guideline on Radiation Therapy for Breast Cancer].

PMID- 16896589
TI  - Postoperative irradiation for pterygium: retrospective analysis of 1,253 patients
      from the Osaka University Hospital.
AB  - BACKGROUND AND PURPOSE: Irradiation of ocular pterygium is considered a valuable
      treatment supplementation after surgical therapy. Since prospective randomized
      trials are scare and only limited patient data are available, the aim of this
      study was to evaluate the patient population treated with fractioned 90Sr
      irradiation after surgical pterygium resection. PATIENTS AND METHODS: Between
      September 1993 and March 2001, 1,147 patients with pterygium lesions (1,320
      lesions) were treated surgically and with 90Sr postoperative beta-irradiation. A
      total dose of 30 Gy was used for patients treated within 48 h after surgery,
      while those treated>48 h postoperatively received a total dose of 35 Gy. A
      minimum follow-up period of 3 months was required for inclusion in the analysis,
      and 1,253 lesions were ultimately analyzed. RESULTS: Recurrence of the pterygium
      after postoperative 90Sr irradiation was observed in 97 of 1,253 cases (7.7%).
      Statistical analysis (uni- and multivariate) revealed, that male gender, younger
      age (<40 years), prior treatment (surgery and radiotherapy) and immediate
      irradiation (<2 h after surgery) were negative predictors for local recurrence.
      Temporary radiotherapy-induced side effects were observed in 15.2% of patients,
      including moderate conjunctivitis, local pain, visual disturbance and photophobia
      or an increase in tear flow. However, no long-term serious side effects were
      documented. CONCLUSION: 90Sr irradiation of pterygium after surgery represents a
      safe and effective treatment option to prevent disease recurrence. The data
      obtained in this study indicate that a certain interval after surgery might
      improve therapy outcome.

PMID- 16896588
TI  - Estimation of cancer risks from radiotherapy of benign diseases.
AB  - BACKGROUND: The effective-dose method which was proposed by the ICRP
      (International Commission of Radiation Protection) for the estimation of risk to
      the general population from occupational or environmental, low-dose radiation
      exposure is not adequate for estimating the risk of cancer induction by
      radiotherapy of malignant or nonmalignant diseases. METHODS: The risk of cancer
      induction by radiotherapy of benign diseases should be based on epidemiologic
      data directly derived from follow-up studies of patients who had been given
      radiotherapy for nonmalignant diseases in the past. RESULTS: Risk factors were
      derived from epidemiologic studies of patients treated with irradiation for
      nonmalignant diseases to be used for selecting treatment options and optimizing
      treatment procedures. CONCLUSION: In most cases, cancer risks estimated by the
      effective-dose method may overestimate the true risks by one order of magnitude,
      yet in other cases even may underestimate it. The proposed method using organ
      specific risk factors may be more suitable for treatment planning.

PMID- 16896590
TI  - [Therapy-associated late effects after irradiation of malignant diseases in
      childhood and adolescence. Feasibility analyses of a prospective multicenter
      register study].
AB  - BACKGROUND AND PURPOSE: Radiogenic late effects in children and adolescents have
      been evaluated retrospectively in most analyses, with small patient numbers. The
      German Group of Pediatric Radiation Oncology (APRO) has generated a concept for a
      prospective evaluation of radiation-associated late effects in childhood. The aim
      of this study was to evaluate the feasibility of a nationwide central database
      for the documentation of radiation parameters and side effects of all children
      treated within therapy protocols of the German Society of Pediatric Oncology and
      Hematology (GPOH). PATIENTS AND METHODS: A study center has been implemented in
      Muenster, the documentation has started in July 2001 in few centers in a pilot
      phase. Since February 2004 the documentation is done countrywide. Detailed
      documentation forms have been designed for treatment parameters and for doses
      applied at organs at risk. Furthermore, a uniform toxicity documentation,
      according to the RTOG/EORTC criteria, was chosen. Patients were reported from the
      study centers of the GPOH to the study center. All information was collected and
      analyzed in the study center. RESULTS: Till July 31, 2005, 438 documentations of
      radiation and 579 toxicity documentations of side effects have been collected in
      the study center. 46 centers for radiotherapy in Germany and one center each in
      Austria and in Switzerland took part in the documentation. The quality of
      documentation regarding completeness and plausibility fulfilled the expected
      criteria in most cases. This feasibility analysis showed that important
      information about organ dose levels and side effects was documented in a large
      number of patients (Figures 1 and 2). CONCLUSION: This prospective evaluation of
      radiotherapy and radiogenic side effects in children and adolescents will allow
      correlating doses at organs at risk and the incidence of acute and late sequelae
      in Germany. Further documentations and a longer follow-up are necessary to obtain
      powerful results.

PMID- 16896591
TI  - The reasons for discrepancies in target volume delineation : a SASRO study on
      head-and-neck and prostate cancers.
AB  - PURPOSE: To understand the reasons for differences in the delineation of target
      volumes between physicians. MATERIAL AND METHODS: 18 Swiss radiooncology centers
      were invited to delineate volumes for one prostate and one head-and-neck case. In
      addition, a questionnaire was sent to evaluate the differences in the volume
      definition (GTV [gross tumor volume], CTV [clinical target volume], PTV [planning
      target volume]), the various estimated margins, and the nodes at risk. Coherence
      between drawn and stated margins by centers was calculated. The questionnaire
      also included a nonspecific series of questions regarding planning methods in
      each institution. RESULTS: Fairly large differences in the drawn volumes were
      seen between the centers in both cases and also in the definition of volumes.
      Correlation between drawn and stated margins was fair in the prostate case and
      poor in the head-and-neck case. The questionnaire revealed important differences
      in the planning methods between centers. CONCLUSION: These large differences
      could be explained by (1) a variable knowledge/interpretation of ICRU
      definitions, (2) variable interpretations of the potential microscopic extent,
      (3) difficulties in GTV identification, (4) differences in the concept, and (5)
      incoherence between theory (i.e., stated margins) and practice (i.e., drawn
      margins).

PMID- 16896592
TI  - Prognostic factors and significance of the revised 6th edition of the AJCC
      classification in patients with locally advanced nasopharyngeal carcinoma.
AB  - PURPOSE: To compare the 4th edition 1992 and 6th edition 2002 of the American
      Joint Committee on Cancer (AJCC) staging systems, to evaluate the
      paranasopharyngeal structures and lymph node involvement, and to define the
      prognostic significance of the above factors to overall survival (OS) in patients
      with locally advanced nasopharyngeal carcinoma (NPC). PATIENTS AND METHODS: CT
      images of 162 patients, who were diagnosed with NPC and received irradiation
      alone or chemotherapy and irradiation, were retrospectively reviewed. CT scans,
      performed prior to and after the completion of treatment, were reviewed. RESULTS:
      The parapharyngeal space was found to be involved very commonly (98%). 50 of 162
      patients (31%) displayed parapharyngeal extension of the tumor to degree A, 59
      patients (36%) showed degree B, and 50 patients (31%) degree C nasopharyngeal
      extension. According to the AJCC 6th edition 2002, patients were distributed into
      stages IIA, IIB, III, IVA, and IVB. By contrast, using the AJCC 4th edition 1992,
      patients were distributed into stages III and IV only. After a median follow up
      of 71.1 months, median survival was 60.7 months, with a 2-year survival rate of
      71.3% and a 3-year survival rate of 62.2%. Multivariate analysis identified age,
      degree of parapharyngeal lateral extension, cavernous-sinus-infiltration, and
      size of infiltrated lymph nodes as independent prognostic factors for OS.
      CONCLUSION: The 6th revision of TNM staging reported herein, provides a more
      uniform distribution of patients between stages. The degree of tumor extension
      into the parapharyngeal space should be considered in future TNM staging
      revisions.

PMID- 16896593
TI  - Combined effect of tumor necrosis factor-alpha and ionizing radiation on the
      induction of apoptosis in 5637 bladder carcinoma cells.
AB  - BACKGROUND AND PURPOSE: Apoptosis can be induced by distinct but overlapping
      pathways. Ionizing radiation induces apoptosis by an "intrinsic", mitochondria
      dependent pathway. Ligation of tumor necrosis factor-(TNF-)alpha, FAS (CD95) or
      TRAIL receptors are typical representatives of an extrinsic, death-receptor
      mediated pathway. In this study the effect of irradiation, treatment with the
      cytokine TNF-alpha, or a combination of both on the induction of apoptosis and
      clonogenic survival of bladder carcinoma cells was investigated. MATERIAL AND
      METHODS: 5637 bladder carcinoma cells were treated with different concentrations
      of recombinant TNF-alpha (0-10 ng/ml), irradiated with single doses ranging from
      0.5 to 10 Gy, or a combination of both modalities. Apoptotic cells were
      quantified by the TUNEL assay up to 96 h following treatment, clonogenic cell
      survival by a clonogenic assay. Synergistic effects of both modalities were
      evaluated using isobolographic analysis. RESULTS: Irradiation of 5637 carcinoma
      cells resulted in a discontinuous dose dependence of the apoptotic fraction with
      a pronounced increase in the range of 0-2 Gy and a slighter increase at 2-10 Gy.
      The percentage of apoptotic carcinoma cells also increased continuously after
      treatment with lower concentrations of TNF-alpha reaching a plateau at
      concentrations of 5.0-10.0 ng/ml. Isobolographic analysis revealed a
      supraadditive interrelationship between irradiation and TNF-alpha in the range
      between 0.005 and 0.5 ng/ml, and an additive effect for TNF-alpha
      concentrations>0.5 ng/ml. The additive effects were confirmed in clonogenic
      survival assays with reduced survival fractions following combined TNF-alpha
      administration and irradiation. CONCLUSION: The combination of two apoptosis
      inducing modalities resulted in a synergistic effect on the induction of
      apoptosis in 5637 bladder carcinoma cells. Although a radiosensitizing effect
      still has to be proven in animal models, combined-modality treatment may increase
      the therapeutic effectiveness of irradiation in bladder cancer.

PMID- 16896594
TI  - Inverse planning--a comparative intersystem and interpatient constraint study.
AB  - PURPOSE: To compare commercial treatment-planning systems (TPS) for inverse
      planning (IP) and to assess constraint variations for specific IMRT indications.
      MATERIAL AND METHODS: For IP, OTP, XiO and BrainSCAN were used and step-and-shoot
      intensity-modulated radiotherapy (IMRT) delivery was assumed. Based on identical
      constraints, IP was performed for a prostate, head and neck, brain, and
      gynecologic case. IMRT plans were compared in terms of conformity/homogeneity,
      dose-volume histograms (DVHs), and delivery efficiency. For ten patients each of
      a class of indications, constraint variations were evaluated. RESULTS: IMRT plans
      were comparable concerning minimum target dose, homogeneity, conformity, and
      maximum doses to organs at risk. Larger differences were seen in dose gradients
      outside the target, monitor units, and segment number. Using help structures
      proved efficient to shape isodoses and to reduce segmentation workload. For IMRT
      class solutions, IP constraint variations depended on anatomic site. CONCLUSION:
      IP systems requiring doses as input and having objective functions based on
      physical parameters had a very similar performance. Constraint templates can be
      established for a class of IMRT indications.

PMID- 16896595
TI  - Intensity-modulated radiation therapy (IMRT) with different combinations of
      treatment-planning systems and linacs: issues and how to detect them.
AB  - PURPOSE: To compare different combinations of intensity-modulated radiation
      therapy (IMRT) system components with regard to quality assurance (QA),
      especially robustness against malfunctions and dosimetry. MATERIAL AND METHODS:
      Three different treatment-planning systems (TPS), two types of linacs and three
      multileaf collimator (MLC) types were compared: commissioning procedures were
      performed for the combination of the TPS Corvus 5.0 (Nomos) and KonRad v2.1.3
      (Siemens OCS) with the linacs KD2 (Siemens) and Synergy (Elekta). For PrecisePLAN
      2.03 (Elekta) measurements were performed for Elekta Synergy only. As record and
      verify (R&V) system Multi-Access v7 (IMPAC) was used. The use of the serial
      tomotherapy system Peacock (Nomos) was investigated in combination with the
      Siemens KD2 linac. RESULTS: In the comparison of calculated to measured dose,
      problems were encountered for the combination of KonRad and Elekta MLC as well as
      for the Peacock system. Multi-Access failed to assign the collimator angle
      correctly for plans with multiple collimator angles per beam. Communication
      problems of Multi-Access with both linacs were observed, resulting in incorrect
      recording of the treatment. All reported issues were addressed by the
      manufacturers. CONCLUSION: For the commissioning of IMRT systems, the whole chain
      from the TPS to the linac has to be investigated. Components that passed the
      commissioning in another clinical environment can have severe malfunctions when
      used in a new environment. Therefore, not only single components but the whole
      chain from planning to delivery has to be evaluated in commissioning and checked
      regularly for QA.

PMID- 16896596
TI  - Tissue microarrays: applications in urological cancer research.
AB  - Tissue microarrays (TMAs) are used to simultaneously study the expression of
      proteins in hundreds of tissue samples, offering the important advantage to
      screen large tissue banks for biomarker expression and to simultaneously examine
      serial sections obtained from the same tumor specimen by a time- and cost
      effective analytical approach. This review article presents an overview of the
      importance and the impact of this technique in cancer research with increasing
      number of investigations using TMAs in its eighth anniversary. Its application,
      limitations, and selected previous study results regarding urologic malignancies
      are presented and discussed.

PMID- 16896597
TI  - Stability of plasmid and expression of a recombinant gonadotropin-releasing
      hormone (GnRH) vaccine in Escherichia coli.
AB  - In our previous studies, the recombinant gonadotropin-releasing hormone (GnRH)
      peptide was constructed into a T7 RNA polymerase-based expression system. The
      recombinant gene encoding GnRH3-hinge-MVP, which contained three repeated GnRH
      units, a fragment of hinge region (225-232/225'-232'), and a T cell epitope of
      measles virus protein, was cloned into Escherichia coli BL21 harboring pED-GnRH3.
      The high activity of T7 RNA polymerase could make the expression system very
      powerful for high-level expression of the recombinant protein. However, during
      the large-scale production of recombinant protein, the productivity of the
      fermentation process was directly affected by many factors, such as plasmid
      stability, protein production, and culture conditions. In this study, we studied
      the effects of various culture conditions on the plasmid stability and the target
      protein yield including selective pressure, the time of induction by lactose, and
      the number of successive cultures. The results indicate that the plasmid
      instability may be caused by a loss of plasmid rather than structural change.
      However, to go down to future generations, engineered bacteria have the stability
      of plasmid and protein yield to a large extent. The amount of the fusion protein
      was also up to 40% of the total cell protein after the 50th generation. These
      data would be useful for the industrial production of the recombinant GnRH
      vaccine.

PMID- 16896598
TI  - Oil biodegradation by Bacillus strains isolated from the rock of an oil reservoir
      located in a deep-water production basin in Brazil.
AB  - Sixteen spore forming Gram-positive bacteria were isolated from the rock of an
      oil reservoir located in a deep-water production basin in Brazil. These strains
      were identified as belonging to the genus Bacillus using classical biochemical
      techniques and API 50CH kits, and their identity was confirmed by sequencing of
      part of the 16S rRNA gene. All strains were tested for oil degradation ability in
      microplates using Arabian Light and Marlin oils and only seven strains showed
      positive results in both kinds of oils. They were also able to grow in the
      presence of carbazole, n-hexadecane and polyalphaolefin (PAO), but not in
      toluene, as the only carbon sources. The production of key enzymes involved with
      aromatic hydrocarbons biodegradation process by Bacillus strains (catechol 1,2
      dioxygenase and catechol 2,3-dioxygenase) was verified spectrophotometrically by
      detection of cis,cis-muconic acid and 2-hydroxymuconic semialdehyde, and results
      indicated that the ortho ring cleavage pathway is preferential. Furthermore,
      polymerase chain reaction (PCR) products were obtained when the DNA of seven
      Bacillus strains were screened for the presence of catabolic genes encoding
      alkane monooxygenase, catechol 1,2-dioxygenase, and/or catechol 2,3-dioxygenase.
      This is the first study on Bacillus strains isolated from an oil reservoir in
      Brazil.

PMID- 16896599
TI  - Degradation of carbazole and its derivatives by a Pseudomonas sp.
AB  - Carbazole, carbazoles with monomethyl or dimethyls substituted on different
      positions (C(1)-carbazoles or C(2)-carbazoles), and benzocarbazoles, as toxic and
      mutagenic components of petroleum and creosote contamination, were biodegradable
      by an isolated bacterial strain Pseudomonas sp. XLDN4-9. C(1)-carbazoles were
      degraded in preference to carbazole and C(2)-carbazoles. The biodegradation of
      C(1)-carbazoles or C(2)-carbazoles was influenced by the positions of methyl
      substitutions. Among C(1)-carbazole isomers, 1-methyl carbazole was the most
      susceptible. C(2)-carbazole isomers with substitutions on the same benzo-nucleus
      were more susceptible at a concentration of less than 3.4 microg g(-1) petroleum,
      especially when harboring one substitution on position 1. In particular, 1,5
      dimethyl carbazole was the most recalcitrant dimethyl isomer.

PMID- 16896600
TI  - Perspectives and advances of biological H2 production in microorganisms.
AB  - The rapid development of clean fuels for the future is a critically important
      global challenge for two main reasons. First, new fuels are needed to supplement
      and ultimately replace depleting oil reserves. Second, fuels capable of zero CO2
      emissions are needed to slow the impact of global warming. This review summarizes
      the development of solar powered bio-H2 production processes based on the
      conversion of photosynthetic products by fermentative bacteria, as well as using
      photoheterotrophic and photoautrophic organisms. The use of advanced bioreactor
      systems and their potential and limitations in terms of process design,
      efficiency, and cost are also briefly reviewed.

PMID- 16896602
TI  - Xylitol dehydrogenase from Candida tropicalis: molecular cloning of the gene and
      structural analysis of the protein.
AB  - Yeasts can metabolize xylose by the action of two key enzymes: xylose reductase
      and xylitol dehydrogenase. In this work, we present data concerning the cloning
      of the XYL2 gene encoding xylitol dehydrogenase from the yeast Candida
      tropicalis. The gene is present as a single copy in the genome and is controlled
      at the transcriptional level by the presence of the inducer xylose. XYL2 was
      functionally tested by heterologous expression in Saccharomyces cerevisiae to
      develop a yeast strain capable of producing ethanol from xylose. Structural
      analysis of C. tropicalis xylitol dehydrogenase, Xyl2, suggests that it is a
      member of the medium-chain dehydrogenase (MDR) family. This is supported by the
      presence of the amino acid signature [GHE]xx[G]xxxxx[G]xx[V] in its primary
      sequence and a typical alcohol dehydrogenase Rossmann fold pattern composed by
      NAD(+) and zinc ion binding domains.

PMID- 16896601
TI  - Molecular cloning and characterization of two intracellular beta-glucosidases
      belonging to glycoside hydrolase family 1 from the basidiomycete Phanerochaete
      chrysosporium.
AB  - cDNAs encoding two glycoside hydrolase family 1 beta-glucosidases (BGL1A and
      BGL1B) were cloned from the basidiomycete Phanerochaete chrysosporium, and the
      substrate specificities of the recombinant enzymes and the expression patterns of
      the two genes were investigated in relation to cellobiose metabolism by the
      fungus. The cDNA sequences contained open reading frames of 1,389 base pairs (bp)
      (bgl1A) and 1,623 bp (bgl1B), encoding 462 and 530 amino acids, respectively.
      Although high sequence identity (65%) was observed between the deduced amino acid
      sequences of the two enzymes, an apparent difference was observed at the C
      terminal region: BGL1B has a 63-amino acid extension, which has no similarity
      with any known protein. Both recombinant enzymes expressed in Escherichia coli
      showed hydrolytic activity towards several beta-glycosidic compounds. However,
      the substrate recognition patterns of the two enzymes were quite different from
      each other. In particular, cellobiose was hydrolyzed more effectively by BGL1B
      than by BGL1A. The expression of the two genes in the fungus was monitored by
      reverse transcription-PCR, which showed that bgl1A was expressed constitutively
      in both glucose- and cellobiose-containing culture, whereas bgl1B was expressed
      in cellobiose culture but was repressed in glucose culture, possibly because of
      carbon catabolite repression. We conclude that BGL1B contributes to cellobiose
      metabolism during cellulose degradation by P. chrysosporium.

PMID- 16896604
TI  - Arthrobacter sp. lipase immobilization for improvement in stability and
      enantioselectivity.
AB  - Arthrobacter sp. lipase (ABL, MTCC no. 5125) is being recognized as an efficient
      enzyme for the resolution of drugs and their intermediates. The immobilization of
      ABL on various matrices for its enantioselectivity, stability, and reusability
      has been studied. Immobilization by covalent bonding on sepharose and silica
      afforded a maximum of 380 and 40 IU/g activity, respectively, whereas sol-gel
      entrapment provided a maximum of 150 IU/g activity in dry powder. The immobilized
      enzyme displayed excellent stability in the pH range of 4-10 and even at higher
      temperature, i.e., 50-60 degrees C, compared to free enzyme, which is unstable
      under extreme conditions. The resolution of racemic auxiliaries like 1-phenyl
      ethanol and an intermediate of antidepressant drug fluoxetine, i.e., ethyl 3
      hydroxy-3-phenylpropanoate alkyl acylates, provided exclusively R-(+) products (
      approximately 99% ee, E=646 and 473), compared to cell free extract/whole cells
      which gave a product with approximately 96% ee (E=106 and 150). The repeated use
      (ten times) of covalently immobilized and entrapped ABL resulted in no loss in
      activity, thus demonstrating its prospects for commercial applications.

PMID- 16896603
TI  - Biochemical characterization of the decaprenyl diphosphate synthase of
      Rhodobacter sphaeroides for coenzyme Q10 production.
AB  - Coenzyme Q(10) (CoQ(10)), like other CoQs of various organisms, plays
      indispensable roles not only in energy generation but also in several other
      processes required for cells' survival. In this study, a gene encoding for a
      decaprenyl diphosphate synthase (Rsdds) was cloned from Rhodobacter sphaeroides
      in Escherichia coli. The in vivo catalytic activity and product specificity of
      Rsdds were compared with those of a counterpart enzyme from Agrobacterium
      tumefaciens (Atdds) in E. coli as a heterologous host. In contrast with Atdds,
      Rsdds showed lower catalytic activity but higher product specificity for CoQ(10)
      production, as indicated by the amount of CoQ(9) formation. The higher product
      specificity of Rsdds was also confirmed by utilizing both Rsdds and Atdds for in
      vitro synthesis of polyprenyl diphosphates. Thin layer chromatography indicated
      that the Rsdds enzyme resulted in relatively much less solanesyl diphosphate
      formation. The purified Rsdds catalyzed the addition of isopentenyl diphosphate
      to dimethyl allyl diphosphate, geranyl diphosphate, omega,E,E-farnesyl
      diphosphate (FPP), and omega,E,E,E-geranylgeranyl diphosphate as priming
      substrates. The kinetic parameters of V (max) (pmol/min), K (M) (microM), k (cat)
      (1/min), and k (cat) /K (M) of the enzyme using FPP as the most appropriate
      substrate were determined to be 264.6, 13.1, 8.8, and 0.67, respectively.

PMID- 16896606
TI  - Expression in Escherichia coli and characterization of beta-xylosidases GH39 and
      GH-43 from Bacillus halodurans C-125.
AB  - To develop xylosidases as tools for the hydrolysis of wheat bran arabinoxylans,
      two beta-xylosidases from Bacillus halodurans C-125 have been cloned and
      expressed in Escherichia coli. The recombinant (His)(6)-tagged enzymes,
      designated as XylBH39 and XylBH43, were efficiently purified using Ni(2+)
      affinity chromatography. Determination of native molecular masses indicated that
      XylBH43 is dimeric in solution, whereas a similar analysis of XylBH39 did not
      allow differentiation between the dimeric and trimeric states. Both enzymes had
      similar pH and temperature optima (pH 7.5 and 55 degrees C for XylBH39 and pH 8
      and 60 degrees C for XylBH43) and were relatively stable over the pH range of 3.5
      8.5. In contrast, XylBH39 was more thermostable. At 60 degrees C, XylBH39 and
      XylBH43 displayed approximate half-life values of 2.40 and 0.05 h, respectively.
      The comparison of the ratio k (cat)/K (M) revealed that XylBH43 hydrolyzed p
      nitrophenyl-beta-D: -xyloside more efficiently (4.6-fold) than XylBH39.
      Similarly, while XylBH43 was 18-fold less active on p-nitrophenyl-alpha-L: 
      arabinofuranoside, XylBH39 was essentially inactive on this substrate. Using
      either p-nitrophenyl-beta-D: -xyloside or xylotriose, XylBH39 performed
      transglycosylation, while xylobiose proved to be a poor substrate for both
      hydrolysis and transglycosylation. The use of XylBH39 and XylBH43 for the
      posttreatment of endoxylanase-generated wheat bran hydrolysates revealed that
      XylBH43 efficiently produced xylose monomers (385 microg/ml after 330 min
      incubation). Its activity was improved by the simultaneous deployment of an alpha
      L: -arabinofuranosidase. Together, these enzymes were able to release 521
      microg/ml of xylose after 330 min. This constitutes an approximate yield
      improvement of 35%.

PMID- 16896605
TI  - Antimicrobial activity of resin acid derivatives.
AB  - The wide potential of resin acids as bioactive agents gave rise to a growing
      effort in the search for new applications of the natural forms and their
      derivatives. In some of these compounds, the antimicrobial activity is associated
      to the presence in the molecules of functional groups such as the hydroxyl,
      aldehyde, and ketone or to their cis or trans configurations. The resin acid
      family covers a spectrum of antimicrobial activities against several
      microorganisms, from bacteria to fungi, in which the mode of action was studied
      by electron microscopy. The morphological alterations are consistent with an
      unspecific mode of action causing inhibition of the fungal growth or damaging the
      fungal cells in parallel with a mechanism of resistance based on the retention of
      the compound by the lipid accumulation. The sterol composition of phytopathogenic
      fungi Botrytis cinerea and Lophodermium seditiosum treated with methyl cis-7-oxo
      deisopropyldehydroabietate revealed the presence of ergosterol (M+ 396) and
      dihydroergosterol (M+ 398) in both cultures showing that this compound did not
      interfere with the ergosterol metabolic pathway of both fungi.

PMID- 16896607
TI  - Hydrogen peroxide-induced astaxanthin biosynthesis and catalase activity in
      Xanthophyllomyces dendrorhous.
AB  - Xanthophyllomyces dendrorhous (formerly Phaffia rhodozyma) in shake-flask
      cultures was exposed to 10-20 mmol/L H(2)O(2) at various culture stages, and the
      astaxanthin production was significantly increased by H(2)O(2) fed at 0 or 24 h
      (exponential phase), but only slightly at 48 h (near stationary phase). The
      astaxanthin production was enhanced most significantly with double feeding of 10
      mmol/L H(2)O(2) at 0 and 24 h, reaching a cellular content of 1.30 mg/g cell and
      a volumetric yield of 10.4 mg/L, which were 83 and 65% higher, respectively, than
      those of the control (0.71 mg/g cell and 6.3 mg/L). The intracellular catalase
      (CAT) activity was also increased after H(2)O(2) treatment. The increases in CAT
      and astaxanthin of cells could be detected within 4 h of H(2)O(2) treatment. The
      increase in the astaxanthin content of cells was concomitant with a notable
      decrease in the beta-carotene content. The older yeast cells at late culture
      stage (120 h), due perhaps in part to their higher astaxanthin contents, were
      more tolerant to H(2)O(2) toxicity than the younger cells (24 h). No enhancement
      of the astaxanthin biosynthesis was attained when H(2)O(2) was added to the yeast
      culture together with a sufficient amount of exogenous CAT. The results suggest
      that astaxanthin biosynthesis in X. dendrorhous can be stimulated by H(2)O(2) as
      an antioxidative response.

PMID- 16896608
TI  - Regulatory T cells.

PMID- 16896609
TI  - Circumventing air bubbles in microfluidic systems and quantitative continuous
      flow PCR applications.
AB  - Polymerase chain reaction (PCR) is an essential part of research based on
      genomics or cell analysis. The development of a microfluidic device that would be
      suitable for high-temperature-based reactions therefore becomes an important
      contribution towards the integration of micro-total analysis systems (muTAS).
      However, problems associated with the generation of air bubbles in the
      microchannels before the introduction of the assay liquid, which we call the
      "initial start-up" in this study, made the flow irregular and unstable. In this
      report, we have tried to address these problems by adapting a novel liquid-flow
      method for high-temperature-based reactions. A PDMS-based microfluidic device was
      fabricated by soft-lithography techniques and placed on a cartridge heater. The
      generation of the air bubbles was prevented by introducing the fluorinated oil,
      an inert and highly viscous liquid, as the cap just before the introduction of
      the sample solutions into the microchannels. The technique was applied for
      continuous-flow PCR, which could perform PCR on-chip in a microfluidic system.
      For the evaluation of practical accuracy, plasmid DNA that serves as a reference
      molecule for the quantification of genetically modified (GM) maize was used as
      the template DNA for continuous-flow PCR. After PCR, the products were collected
      in a vial and analyzed by gel electrophoresis to confirm the accuracy of the
      results. Additionally, quantitative continuous-flow PCR was performed using
      TaqMan technology on our PCR device. A laser detection system was also used for
      the quantitative PCR method. We observed a linear relationship between the
      threshold cycle (Ct) and the initial DNA concentration. These results showed that
      it would be possible to quantify the initial copies of the template DNA on our
      microfluidic device. Accurate quantitative DNA analysis in microfluidic systems
      is required for the integration of PCR with muTAS, thus we anticipate that our
      device would have promising potential for applications in a wide range of
      research.

PMID- 16896610
TI  - Chemical vapor generation of noble metals for analytical spectrometry.
AB  - As is apparent from the literature devoted to the analytical atomic spectrometry,
      chemical vapor generation (CVG) of noble metals by reaction with tetrahydroborate
      in acidic media may enhance the introduction of these elements into different
      atomic spectrometric sources. Recent developments in the CVG of noble metals
      species by reaction with tetrahydroborate in acidic medium are surveyed.
      Different aspects of this novel technique are discussed, including type of
      instrumentation used for the reaction, separation and transport of the species,
      effect of chemical and physical factors, identification of the species, and the
      efficiency of the process. Limitations and future prospects of the CVG technique
      are discussed.

PMID- 16896611
TI  - Use of LIBS for rapid characterization of parchment.
AB  - Parchment from different sources has been analyzed by laser-induced breakdown
      spectroscopy (LIBS) for determination of Ca, Na, K, Mg, Fe, Cu, and Mn. The LIBS
      results were compared with results from inductively coupled plasma spectroscopy
      (ICP) and good correlation was obtained. Rapid distinction between modern and
      historical samples was achieved by discriminant analysis of the LIBS data. Animal
      type recognition was also possible on the basis of Mg/Cu emission peak ratio and
      Mg depth profiling.

PMID- 16896612
TI  - Experimental parameters affecting sensitivity and specificity of a yeast assay
      for estrogenic compounds: results of an interlaboratory validation exercise.
AB  - In vitro assays are considered as the first step in a tiered approach to compound
      screening for hormonal activity. Although many new assays have been developed in
      recent years, little attention has been paid towards assay validation. Our
      objective was to identify critical experimental parameters in a yeast estrogen
      screen (YES) that affect its sensitivity and specificity. We investigated the
      role of incubation time, solvent type, yeast inoculum growth stage and
      concentration on the outcome of the YES. Compounds tested included new and
      established agonists, antagonists and negative controls, and results were
      evaluated according to prefixed statistical criteria. In addition, we assessed
      the assay's performance in a blind interlaboratory validation exercise (IVE). An
      incubation time of five days was necessary to positively identify the estrogenic
      properties of all agonists tested, when dissolved in DMSO. Longer incubation
      times were required when using an ethanol protocol. Similar estrogenic activity
      was reported for benzyl butyl phthalate, bisphenol-A, methoxychlor, permethrin
      and genistein in the IVE. One out of the three laboratories did not classify
      alpha,beta-endosulfan, dissolved in DMSO, as an estrogen. The same was true for
      4,4'-DDE and lindane, dissolved in ethanol, a result that might be attributable
      to an inappropriate yeast start concentration and/or growth stage. These
      validation experiments show that under appropriate experimental conditions the
      YES yields sensitive, specific and reliable results. Therefore it fulfills the
      requirements as a first step screening assay to evaluate the capacity of
      chemicals to interact with the estrogen receptor.

PMID- 16896613
TI  - Methylmercury determination in biological samples using electrothermal atomic
      absorption spectrometry after acid leaching extraction.
AB  - An efficient and sensitive method for the determination of methylmercury in
      biological samples was developed based on acid leaching extraction of
      methylmercury into toluene. Methylmercury in the organic phase was determined by
      electrothermal atomic absorption spectrometry (ETAAS). The methylmercury signal
      was enhanced and the reproducibility increased by formation of certain complexes
      and addition of Pd-DDC modifier. The complex of methylmercury with DDC produced
      the optimum analytical signal in terms of sensitivity and reproducibility
      compared to complexes with dithizone, cysteine, 1,10-phenanthroline, and
      diethyldithiocarbamate. Method performance was optimized by modifying parameters
      such as temperature of mineralization, atomization, and gas flow rate. The limit
      of detection for methylmercury determination was 0.015 mug g(-1) and the RSD of
      the whole procedure was 12% for human teeth samples (n=5) and 15.8% for hair
      samples (n=5). The method's accuracy was investigated by using NIES-13 and by
      spiking the samples with different amounts of methylmercury. The results were in
      good agreement with the certified values and the recoveries were 88-95%.

PMID- 16896614
TI  - Optimisation of pressurised liquid extraction for the determination of p,p'-DDT
      and p,p'-DDE in aged contaminated Ethiopian soils.
AB  - The effectiveness of extracting p,p'-DDT and p,p'-DDE from aged contaminated soil
      samples by means of pressurized liquid extraction (PLE) was evaluated. Two soil
      samples, which were contaminated more than 10 years ago, were used in the
      investigation. The static extraction time was optimised and then validated
      against the total sum of target analytes obtained from multiple sequential
      extractions. The PLE results were also compared with Soxhlet extraction (SOX).
      PLE for 3x10 min at 100 degrees C was proven to be more exhaustive than SOX in
      the determination of p,p'-DDE from both soil samples. In the case of p,p'-DDT,
      PLE was found to be equally as exhaustive as SOX. Additionally, most of the
      previous PLE investigations used hazardous organic solvents such as n-hexane,
      toluene and dichloromethane mixed with acetone, whereas in this investigation the
      less toxic solvent combination n-heptane/acetone has been employed.

PMID- 16896616
TI  - Emission-based optical carbon dioxide sensing with HPTS in green chemistry
      reagents: room-temperature ionic liquids.
AB  - We describe the characterization of a new optical CO(2) sensor based on the
      change in the fluorescence signal intensity of 8-hydroxypyrene-1,3,6-trisulfonic
      acid trisodium salt (HPTS) in green chemistry reagents--room-temperature ionic
      liquids (RTILs). As far as we are aware, this is the first time RTILs, 1-methyl-3
      butylimidazolium tetrafluoroborate (RTIL-I) and 1-methyl-3-butylimidazolium
      bromide (RTIL-II), have been used as matrix materials with HPTS in an optical
      CO(2) sensor. It should be noted that the solubility of CO(2) in water-miscible
      ionic liquids is approximately 10 to 20 times that in conventional solvents,
      polymer matrices, or water. The response of the sensor to gaseous and dissolved
      CO(2) has been evaluated. The luminescence intensity of HPTS at 519 and 521 nm
      decreased with the increasing concentrations of CO(2) by 90 and 75% in RTIL-I and
      RTIL-II, respectively. The response times of the sensing reagents were in the
      range 1-2 min for switching from nitrogen to CO(2), and 7-10 min for switching
      from CO(2) to nitrogen. The signal changes were fully reversible and no
      significant hysteresis was observed during the measurements. The stability of
      HPTS in RTILs was excellent and when stored in the ambient air of the laboratory
      there was no significant drift in signal intensity after 7 months. Our stability
      tests are still in progress.

PMID- 16896617
TI  - Determination of butyltin and octyltin stabilizers in poly(vinyl chloride)
      products by headspace solid-phase microextraction and gas chromatography with
      flame-photometric detection.
AB  - Headspace solid-phase microextraction (HS-SPME) and gas chromatography with flame
      photometric detection (GC-FPD) have been investigated for determination of
      butyltin and octyltin stabilizers in poly(vinyl chloride) (PVC) products. The
      organotin stabilizers were first released from the plastic matrix by dissolving
      the PVC sample in tetrahydrofuran (THF). The stabilizers were then hydrolyzed to
      the chloride forms, by treatment with 6 mol L(-1) HCl, then derivatized with
      sodium tetraethylborate (NaBEt4) in 0.2 mol L(-1) sodium acetate buffer (pH 4.5)
      at 50 degrees C. HS-SPME was performed with a fused-silica fiber coated with a
      100-microm film of polydimethylsiloxane (PDMS). The collected organotin compounds
      were then desorbed in the GC injector at 280 degrees C and analyzed by GC-FPD.
      Linearity (r > or =0.994) over a concentration of approximately two orders of
      magnitude was usually obtained. Limits of quantitation (LOQ) of the four
      organotin compounds studied, viz., monobutyltin (MBT), dibutyltin (DBT),
      monooctyltin (MOT), and dioctyltin (DOT), were in the range 0.3-1.0 ng Sn mL(-1).
      Recovery was >90% for butyltins and >80% for octyltins. The method was validated
      by analyzing two reference standard PVC sheets with known organotin content. The
      applicability of the method to analysis of organotin stabilizers in commercial
      PVC products was also demonstrated.

PMID- 16896618
TI  - Analysis of oxidized multi-walled carbon nanotubes in single K562 cells by
      capillary electrophoresis with laser-induced fluorescence.
AB  - Short oxidized multi-walled carbon nanotubes (CNT) were derivatized with
      fluorescein isothiocyanate (FITC). Capillary electrophoresis coupled with laser
      induced fluorescence (CE-LIF) was then used to separate and detect the
      fluorescently labeled carbon-nanotube probes (CNTP) in multidrug-resistant cells
      (K562A) and the parent cells (K562S). Greater expression of P-glycoprotein in
      K562A cells than in K562S cells was confirmed by use of anti-P-glycoprotein
      antibody and flow-cytometric analysis. Analyses of CNTP in both cell lines using
      both CE-LIF and flow cytometry showed that CNTP could traverse the cellular
      membrane without being pumped out by P-glycoprotein. The CNTP distributed in both
      cell lines was analyzed at the single cell level and the results were compared
      with those from analysis of ten cells and of the lysate from bulk cells. The
      results revealed the CE-LIF method could be used for quantitative analysis of CNT
      in single cells in studies of drug delivery and multidrug resistance.

PMID- 16896620
TI  - Solution to Goldberg variations challenge.

PMID- 16896621
TI  - Fluorometry of hydrogen peroxide using oxidative decomposition of folic acid.
AB  - Hydrogen peroxide (H2O2) is one of the most important reactive oxygen species. In
      the present study, a fluorometry method for detecting H2O2 utilizing folic acid
      was evaluated. Folic acid was decomposed by H2O2 in the presence of Cu(II) into
      pterine-6-carboxylic acid, leading to strong fluorescence enhancement. In the
      absence of the metal ion, superoxide and H2O2 could not decompose folic acid.
      Also, H2O2 plus sodium hypochlorite (a source of singlet oxygen) could not induce
      fluorescence enhancement. These results demonstrate that H2O2 can be selectively
      detected using folic acid plus Cu(II). The limit of detection (LOD; at S/N=3) for
      H2O2 is 0.5 microM. This method based on the fluorescence enhancement of folic
      acid was applied in order to determine small amounts of H2O2 generated through
      the autooxidation of semicarbazide (generation rate: approximately 0.01 microM
      min(-1)), a carcinogenic compound.

PMID- 16896622
TI  - Pressurized liquid extraction in environmental analysis.
AB  - A critical evaluation of recent literature utilizing pressurized liquid
      extraction (PLE) for environmental analysis is presented by compound class.
      Overall, the extraction efficiency of PLE, using the appropriate solvent,
      temperature and pressure for extraction, is similar to that of Soxhlet
      extraction. PLE has been used for some classes of compounds that are thermally
      labile (e.g., explosives) and may require acidic conditions for extraction (e.g.,
      organometallic compounds). References to recent applications are presented
      emphasizing studies which utilize unspiked, natural matrices and studies that
      compare PLE to alternate extraction techniques.

PMID- 16896623
TI  - Application of glow discharge mass spectrometry to multielement ultra-trace
      determination in ultrahigh-purity copper and iron: a calibration approach
      achieving quantification and traceability.
AB  - A new approach was developed for quantitative calibration in GD-MS which can
      afford reliable and metrologically traceable results for many trace elements and
      was exemplified for pure copper and pure iron. It can be assumed that the
      technique can be further improved and applied to the analysis of other pure
      metals. Pressed copper and iron powder samples were used to calibrate the glow
      discharge mass spectrometry applied to the analysis of pure copper and iron. The
      new type of glow discharge mass spectrometer--the Element GD (Thermo Electron
      Corporation)--was used with a Grimm-type discharge cell for flat samples. Two
      series of powder samples were prepared for each of the copper and iron matrixes.
      The powders were quantitatively doped with solutions of graduated and defined
      concentrations of 40 or 20 analytes, respectively. The mass fractions of the
      analytes in the dried and homogenized metal powder samples ranged from microg/kg
      levels up to 10 mg/kg levels. A special technique was developed to press the
      samples and to form mechanically stable pellets with low risk of contamination.
      Ion beam ratios of analyte ions to matrix ions were used as measurands. The
      calibration curves were determined and the linear correlation coefficients were
      calculated for different intervals of the curves. The linear correlation
      coefficients are very satisfactory for most of the calibration curves, which
      include the higher segments of mass fractions; however, they are less
      satisfactory for the lower segments of the calibration curves. Nevertheless, in
      many cases rather acceptable and rather promising values were achieved even for
      these lower segments, representing mass fractions of analytes at ultra-trace
      level. The comparison of the certified values of different reference materials
      with the measured values based on calibrations with the pressed powder samples
      led to deviations less than 30% for most of the considered examples.

PMID- 16896624
TI  - C and N stable isotope variation in urine and milk of cattle depending on the
      diet.
AB  - The stable carbon and nitrogen isotopic composition of urine and milk samples
      from cattle under different feeding regimes were analysed over a period of six
      months. The isotope ratios were measured with isotope ratio mass spectrometry
      (IRMS). The delta13C values of milk and urine were dependent on different feeding
      regimes based on C3 or C4 plants. The delta13C values are more negative under
      grass feeding than under maize feeding. The delta 13C values of milk are more
      negative compared to urine and independent of the feeding regime. Under grass
      feeding the analysed milk and urine samples are enriched in 13C relative to the
      feed, whereas under maize feeding the 13C/12C ratio of urine is in the same range
      and milk is depleted in 13C relative to the diet. The difference between the
      15N/14N ratios for the two feeding regimes is less pronounced than the 13C/12C
      ratios. The delta 15N values in urine require more time to reach the new
      equilibrium, whereas the milk samples show no significant differences between the
      two feeding regimes.

PMID- 16896625
TI  - Combined FT-Raman spectroscopic and mass spectrometric study of ancient Egyptian
      sarcophagal fragments.
AB  - The application of combined Raman spectroscopic and GC-MS analytical techniques
      for the characterisation of organic varnish residues from Egyptian Dynastic
      funerary sarcophagal and cartonnage fragments from the Graeco-Roman period, ca.
      2200 BP, is described. The nondestructive use of Raman spectroscopy was initially
      employed to derive information about the specific location of organic material on
      the specimens, which were then targeted in specific areas using minimal sampling
      for GC-MS analysis. In the case of the sarcophagal fragment, a degraded yellow
      brown surface treatment was identified as a Pistacia spp. resin; this provides
      additional evidence for the use of this resin, which has previously been
      identified in Canaanite transport amphorae, varnishes and "incense" bowls in an
      Egyptian Late Bronze Age archaeological context. The cartonnage fragment also
      contained an organic coating for which the Raman spectrum indicated a degradation
      that was too severe to facilitate identification, but the GC-MS data revealed
      that it was composed of a complex mixture of fatty acid residues. The combined
      use of GC-MS and Raman spectroscopy for the characterisation of organic materials
      in an archaeological context is advocated for minimisation of sampling and
      restriction to specifically identified targets for museum archival specimens.

PMID- 16896626
TI  - Advanced CPMAS-13C NMR techniques for molecular characterization of size
      separated fractions from a soil humic acid.
AB  - A humic acid extracted from a volcanic soil was subjected to preparative high
      performance size-exclusion chromatography (HPSEC) to reduce its molecular
      complexity and eleven different size fractions were obtained. Cross-polarization
      magic-angle spinning 13C NMR (CPMAS 13C NMR) analysis performed with variable
      contact-time (VCT) pulse sequences showed that the largest molecular-size
      fractions contained aromatic, alkyl, and carbohydrate-like components. The
      carbohydrate-like content and the alkyl chain length seemed to decrease with
      decreasing molecular size. Progressive reduction of aromatic carbon atoms was
      also observed with decreasing molecular size of the separated fractions.
      Mathematical treatment of the results from VCT experiments enabled cross
      polarization (T (CH)) and proton spin-lattice relaxation (T(1rho)(H)) times to be
      related to structural differences among the size fractions. The conformational
      distribution indicated that the eleven size fractions could be allocated to two
      main groups. The first group, with larger nominal molecular sizes, was
      characterized by molecular domains with slower local molecular motion. The second
      group of size fractions, with smaller nominal molecular sizes, was characterized
      by a larger number of molecular domains with faster local molecular motion. The T
      (CH) and (T(1rho)(H)) values suggested that either condensed or strongly
      associated aromatic systems were predominant in the size fractions with the
      largest apparent molecular dimensions.

PMID- 16896627
TI  - Analysis of odorous trichlorobromophenols in water by in-sample
      derivatization/solid-phase microextraction GC/MS.
AB  - The simultaneous determination of several odorous trichlorobromophenols in water
      has been carried out by an in-sample derivatization headspace solid-phase
      microextraction method (HS-SPME). The analytical procedure involved their
      derivatization to methyl ethers with dimethyl sulfate/NaOH and further HS-SPME
      and gas chromatography-mass spectrometry (GC/MS) determination. Parameters
      affecting both the derivatization efficiency and headspace SPME procedures, such
      as the selection of the SPME fiber coating, derivatization-extraction time and
      temperature, were studied. The commercially available polydimethylsiloxane (PDMS)
      100 microm and Carboxen-polydimethylsiloxane-divinylbenzene (CAR-PDMS-DVB) fibers
      appeared to be the most suitable for the simultaneous determination of these
      compounds. The precision of the HS-SPME/GC/MS method gave good relative standard
      deviations (RSDs) run-to-run between 9% and 19% for most of them, except for 2,5
      diCl-6-Br-phenol, 2,6-diCl-3-Br-phenol and-2,3,6-triBr-phenol (22%, 25% and 23%,
      respectively). The method was linear over two orders of magnitude, and detection
      limits were compound dependent but ranged from 0.22 ng/l to 0.95 ng/l. The
      results obtained for water samples using the proposed SPME procedure were
      compared with those found with the EPA 625 method, and good agreement was
      achieved. Therefore, the in-sample derivatization HS-SPME/GC/MS procedure here
      proposed is a suitable method for the simultaneous determination of odorous
      trichlorobromophenols in water.

PMID- 16896628
TI  - Combined use of ESI-QqTOF-MS and ESI-QqTOF-MS/MS with mass-spectral library
      search for qualitative analysis of drugs.
AB  - The potential of the combined use of ESI-QqTOF-MS and ESI-QqTOF-MS/MS with mass
      spectral library search for the identification of therapeutic and illicit drugs
      has been evaluated. Reserpine was used for standardizing experimental conditions
      and for characterization of the performance of the applied mass spectrometric
      system. Experiments revealed that because of the mass accuracy, the stability of
      calibration, and the reproducibility of fragmentation, the QqTOF mass
      spectrometer is an appropriate platform for establishment of a tandem-mass
      spectral library. Three-hundred and nineteen substances were used as reference
      samples to build the spectral library. For each reference compound, product-ion
      spectra were acquired at ten different collision-energy values between 5 eV and
      50 eV. For identification of unknown compounds, a library search algorithm was
      developed. The closeness of matching between a measured product-ion spectrum and
      a spectrum stored in the library was characterized by a value called "match
      probability", which took into account the number of matched fragment ions, the
      number of fragment ions observed in the two spectra, and the sum of the intensity
      differences calculated for matching fragments. A large value for the match
      probability indicated a close match between the measured and the reference
      spectrum. A unique feature of the library search algorithm-an implemented
      spectral purification option-enables characterization of multi-contributor
      fragment-ion spectra. With the aid of this software feature, substances
      comprising only 1.0% of the total amount of binary mixtures were unequivocally
      assigned, in addition to the isobaric main contributors. The spectral library was
      successfully applied to the characterization of 39 forensic casework samples.

PMID- 16896630
TI  - Microheterogeneity evaluation of polycyclic aromatic hydrocarbons in particulate
      standard reference materials.
AB  - With the emergence of highly sensitive analytical techniques, the microanalysis
      of natural-matrix materials employing smaller sample sizes is increasingly more
      common, which subsequently warrants a homogeneity assessment for the individual
      components at the appropriate sampling level. Pressurized liquid extraction (PLE)
      in combination with gas chromatography/mass spectrometry (GC/MS) has been used to
      determine the sampling constants and evaluate the relative homogeneity of trace
      levels of polycyclic aromatic hydrocarbons (PAHs) for two previously certified
      particulate standard reference materials, SRM 1649a Urban Dust and SRM 1650b
      Diesel Particulate Matter, in the milligram sampling range. Fluoranthene, pyrene,
      benz[a]anthracene and benzo[e]pyrene within SRM 1650b Diesel Particulate Matter
      were deemed to be homogeneous, based on relatively small sampling constants (K
      (S)<100 mg), whereas the larger sampling constants (K (S)>100 mg) obtained for
      all PAHs in SRM 1649a Urban Dust suggest more material heterogeneity. The
      material heterogeneity of ten individual PAHs (phenanthrene, anthracene,
      fluoranthene, pyrene, benz[a]anthracene, benzo[k]fluoranthene, benzo[e]pyrene,
      benzo[a]pyrene, indeno[1,2,3-cd]pyrene and benzo[ghi]perylene) was also described
      via nonlinear relationships (i.e., power law) between subsampling error S (s) (%)
      and sample mass, which are used to predict analyte-specific minimum sample masses
      that result in a specific level of analytical uncertainty.

PMID- 16896629
TI  - Optimization of solid-phase microextraction procedures for the determination of
      tricyclic antidepressants and anticonvulsants in plasma samples by liquid
      chromatography.
AB  - Simple, sensitive, and reproducible off-line solid-phase microextraction and
      liquid chromatography (SPME/LC) methods are described for the determination of
      seven anticonvulsants and tricyclic antidepressants in human plasma. Factorial
      design and simplex methodology were applied in the optimization of the SPME
      procedure for tricyclic antidepressants analyses. Important factors in the SPME
      efficiency are discussed, such as the fiber coatings (both lab-made and
      commercial), extraction time, pH, ionic strength, influence of plasma proteins,
      and desorption conditions. The development of the lab-made fiber coatings,
      namely, octadecylsilane, aminosilane, and polyurethane, are further described and
      applied to anticonvulsants analyses. The investigated plasmatic range for the
      evaluated anticonvulsants, using CW-TPR fiber, were the following:
      phenylethylmalonamide (3.00-40.0 microg mL(-1)), phenobarbital (5.00-40.0 microg
      mL(-1)), primidone (3.00-40.0 microg mL(-1)), carbamazepine and carbamazepine
      epoxide (2.00-24.0 microg mL(-1)), phenytoin (2.00-40.0 microg mL(-1)), and
      lamotrigine (0.50-12.0 microg mL(-1)). The antidepressants' linear plasmatic
      concentration ranged from 75.0 to 500 ng mL(-1) for imipramine, amitriptyline,
      and desipramine, and from 50.0 to 500 ng mL(-1) for nortriptyline, being in all
      cases, the limit of quantification represented by the lowest value. The precision
      (interassays) for all investigated drugs in plasma sample spiked with different
      concentrations of each analyte and submitted to the described procedures were
      lower than 15%. The off-line SPME/LC methodologies developed allow
      anticonvulsants and antidepressants analyses from therapeutic to toxic levels for
      therapeutic drug monitoring.

PMID- 16896631
TI  - Electrospray mass spectrometry analysis of dendritic branches bearing peripheral
      fullerene subunits.
AB  - The electrospray mass spectrometric characterization of neutral dendrons with a
      carboxylic acid function or a t-butyl ester moiety at the central point and up to
      eight peripheral C60 subunits has been performed and is described in detail.
      Molecules bearing a carboxylic acid group at the center turned out to be
      preferentially ionized by deprotonation, whereas those with a t-butyl ester head
      group were ionized by reduction of the C60 units in the infusion capillary of the
      electrospray source.

PMID- 16896632
TI  - ABCs of teaching analytical sciences. Tips for effective poster presentations.

PMID- 16896633
TI  - Rapid analysis of native neomycin components on a portable capillary
      electrophoresis system with potential gradient detection.
AB  - A simple method based on capillary electrophoresis with potential gradient
      detection was developed to separate and detect neomycin components within 4 min
      without a derivatization step. Satisfactory separation and good repeatability
      were obtained using a separation buffer composed of 1 mM ammonium citrate (pH
      3.5). The linearity of the method ranged from 10 to 1000 ppm with a limit of
      detection for neomycin B of about 7 ppm. After a simple dilution and filtering
      pretreatment step, neomycin components in three real samples were successfully
      analyzed without any major interference. Due to its simplicity and reliability,
      this method could provide an excellent alternative to the assays currently listed
      in U.S. and European Pharmacopoeia. The experiments were performed on a portable
      capillary electrophoresis system and, hence, the method can be readily applied to
      field analysis and point-of-care testing. Figure Photo of portable CE-P2-PGD
      system.

PMID- 16896634
TI  - [Health economy in cardiovascular imaging].
AB  - New medical treatment methods and procedures usually cause high additional costs.
      Medical progress in cardiovascular imaging may fortunately reduce costs
      considerably. In Innsbruck it is calculated that about 1000 euros may be saved
      when replacing diagnostic coronary angiography (CAG) by CT coronary angiography
      (CTA). If in Austria 30% of CAGs are replaced by CTAs with a 64-slice CT system,
      about 13 million euros may be saved provided that CAG capacities will be reduced
      to the same extent as CTAs are done.

PMID- 16896635
TI  - [Diagnostic imaging of inflammatory and tumorous diseases of the colon].
AB  - The detection of inflammatory and tumorous conditions of the colon is one of the
      main topics in current abdominal radiology. The barium enema was introduced first
      in 1923 by Fischer, and has represented the workhorse of intestinal diagnostics
      for decades. The widespread use of endoscopy and the ongoing technical
      improvements in CT and MRI, however, have led to an inevitable displacement of
      this technique. Nevertheless, radiographs and enema are frequently employed in
      the initial work-up of patients with suspected colonic disease. This article
      provides an overview of the most important entities of inflammatory and tumorous
      changes of the colon.

PMID- 16896636
TI  - [Functional anatomy and biomechanics of the carpus].
AB  - The wrist is an exceedingly complex structure composed of several joints and a
      dedicated ligamentous system. Its functional principles allow a wide range of
      carpal motion and make the wrist remarkably resistant to external stress
      forces:The proximal carpal row serves as an intercalated link interposed between
      the static elements of both the forearm and the distal carpal row. Like a
      flexible place-holder, the proximal row synchronously adapts to the spatial and
      temporal requirements of the wrist. There are synergistic movement patterns
      including simultaneous flexion of the proximal row as the wrist is deviated
      radially and simultaneous extension during ulnar deviation. Together with
      pronosupination of the radioulnar joints, the combined radial/ulnar inclination
      and flexion/extension enable spherical, out-of-plane movements of the hand.
      Carpal function is best explained by the "model of a ring under tension."This
      review addresses the anatomy and the biomechanics of the wrist and illustrates
      systematic image analysis by using carpal lines and angles as well as indices of
      carpal height.

PMID- 16896637
TI  - [Quantitative ultrasound].
AB  - Methods of quantitative ultrasound (QUS) can be used to obtain knowledge about
      bone fragility. Comprehensive study results exist showing the power of QUS for
      the estimation of osteoporotic fracture risk. Nevertheless, the variety of
      technologies, devices, and variables as well as different degrees of validation
      of the single devices have to be taken into account. Using methods to simulate
      ultrasound propagation, the complex interaction between ultrasound and bone could
      be understood and the propagation could be visualized. Preceding widespread
      clinical use, it has to be clarified if patients with low QUS values will profit
      from therapy, as it has been shown for DXA. Moreover, the introduction of quality
      assurance measures is essential. The user should know the limitations of the
      methods and be able to interpret the results correctly. Applied in an adequate
      manner QUS methods could then, due to lower costs and absence of ionizing
      radiation, become important players in osteoporosis management.

PMID- 16896638
TI  - [Vertebroplasty and kyphoplasty in patients with osteoporotic fractures: secured
      knowledge and open questions].
AB  - Cementoplasty, performed either as percutaneous vertebroplasty or kyphoplasty,
      has become well established as an effective technique to treat painful vertebral
      body fractures. It has low complication rates, is successful in alleviating pain,
      and improves the patients' mobility and quality of life. A series of questions
      remain open though or are the subject of controversial debate; for example, the
      results of several biomechanical studies are in part contradictory. Clinical data
      on subsequent fractures are also still inadequate, although the majority of
      studies show no elevated rate of subsequent fractures following treatment with
      cementoplasty in comparison to the natural course in patients with osteoporotic
      fractures. Kyphoplasty has the advantage of being able to restore the vertebral
      body height or reduce the kyphosis angle without leading to different clinical
      outcomes in comparison to vertebroplasty. Biomechanical considerations on whether
      restoration of the vertebral body's normal shape could reduce the rate of
      subsequent fractures still need scientific substantiation. Both surgical methods
      are employed in our clinic. Kyphoplasty seems to us to be indicated when the
      height of the anterior portion of the vertebral body is reduced by one-third
      compared to the norm or a kyphosis angle of more than 15-20 degrees is present.
      The goals of therapy are restoring the shape and reducing the kyphosis angle.
      This can only succeed, however, in fractures that are not older than 3 weeks. In
      all other cases vertebroplasty is performed.

PMID- 16896639
TI  - A scoring system to predict chronic oxygen dependency.
AB  - INTRODUCTION: Chronic oxygen dependency (COD) is a common adverse outcome of very
      premature birth. It is, therefore, important to develop an accurate and simple
      predictive test to facilitate targeting of interventions to prevent COD. Our aim
      was to determine if a simple score based on respiratory support requirements
      predicted COD development. METHODS: A retrospective study of 136 infants, median
      gestation age (GA) 28 weeks (range: 23-33 weeks) and a prospective study of 75
      infants, median GA 30 weeks (range: 23-32 weeks), were performed. The score was
      calculated by multiplying the inspired oxygen concentration by the level of
      respiratory support (mechanical ventilation: 2.5; continuous positive airway
      pressure: 1.5; nasal cannula or head box oxygen or air: 1.0). Scores were
      calculated on data from days 2 and 7, and their predictive ability compared to
      that of the maximum inspired oxygen concentration at those ages and
      (retrospective study) the results of lung volume measurement. RESULTS: Infants
      that were oxygen dependent at 28 days and 36 weeks post-menstrual age (PMA) had
      higher scores on days 2 (p<0.0001, p<0.0001, respectively) and 7 (p<0.0001,
      p<0.0001, respectively) than the non-oxygen dependent infants in both the
      retrospective and prospective cohorts. Construction of receiver operator
      characteristic curves demonstrated the score performed better than the inspired
      oxygen level and lung volume measurement results. A score on day 7 >0.323 had 95%
      specificity and 78% sensitivity in predicting COD at 28 days, and 80% specificity
      and 73% sensitivity in predicting COD at 36 weeks PMA. CONCLUSION: Chronic oxygen
      dependency can be predicted using a simple scoring system.

PMID- 16896640
TI  - Pyogenic sacroiliitis in a 14-year-old girl.

PMID- 16896641
TI  - Prediction of non-responsiveness to standard high-dose gamma-globulin therapy in
      patients with acute Kawasaki disease before starting initial treatment.
AB  - Clinical, laboratory, and echocardiographic data were retrospectively analyzed in
      112 patients with acute Kawasaki disease who received high-dose (2 g/kg)
      intravenous gamma-globulin (IVIG) treatment within 2 days and were compared for
      those who were responsive and non-responsive to initial IVIG treatment. Coronary
      arteries adjusted for body surface area (BSA) were evaluated quantitatively by
      comparison with the mean dimensions for 85 normal control subjects. The incidence
      of coronary abnormalities was higher in IVIG-non-responsive patients as compared
      to IVIG-responsive patients (71% versus 5%, p<0.0001). Univariate analysis of pre
      IVIG data showed that the neutrophil count and serum levels of C-reactive protein
      (CRP), total bilirubin (TB), aspartate aminotransferase (AST), alanine
      aminotransferase, and lactate dehydrogenase (LDH) were significantly higher in
      IVIG-non-responsive versus responsive patients. Multivariate analysis selected
      CRP (p=0.009), TB (p<0.001), and AST (p=0.002) as independent predictors of non
      responsiveness to initial IVIG treatment. By defining predictive values, patients
      with at least two of three predictors (CRP>or=7.0 mg, TB>or=0.9 mg, or AST>or=200
      IU/L) are considered to be non-responsive to IVIG for acute Kawasaki disease.
      Alternatively, more intense initial therapy may be a promising therapeutic
      strategy for patients who are predicted to be IVIG-non-responsive.

PMID- 16896642
TI  - Persistent B-cell depletion after rituximab for thrombocytopenic purpura.

PMID- 16896643
TI  - Heroin withdrawal leads to metabolic alkalosis in an infant with cystic fibrosis.

PMID- 16896644
TI  - Three new cases of congenital agenesis of the trachea.
AB  - Congenital absence of the trachea is a rare anomaly that might confront the
      obstetrician or neonatologist with an unexpected emergency. These patients
      present with cyanosis, severe respiratory distress, insufficient gas exchange,
      absence of audible crying and difficult or impossible endotracheal intubation. In
      more than 90% it is associated with further congenital malformations. Adequate
      oxygenation depends on the existence of a tracheo- or bronchooesphageal fistula
      and the length of the proximal trachea. We present the cases of three neonates
      with tracheal agenesis with tracheooesophageal fistula. Two of the neonates died
      within the first hour of life because endotracheal intubation was impossible and
      oxygenation through an oesophageally placed tube was insufficient. The third
      infant could be oxygenated through a tracheooesophageal fistula. The ventilation
      was at least insufficient and no surgical intervention was made. The diagnosis of
      a congenital absence of the trachea usually is made after birth because of the
      clinical signs and the course within the first minutes of life. The only way that
      the diagnosis can be made prenatally is by magnetic resonance imaging (MRI). The
      knowledge of this clinical picture helps to make decisions in an unexpected
      emergency in the immediate postpartum period and also in patients whose
      ventilation is very difficult right from the start.

PMID- 16896645
TI  - The high scrotal ("gliding") testis revised.
AB  - BACKGROUND: At present, the high scrotal testis is considered a distinct and
      separate entity of undescended testis. OBJECTIVES: The aim of this study was to
      assess whether high scrotal testis is actually either a congenital- or acquired
      undescended testis. DISCUSSION: In 527 consecutive boys (aged 0.4 to 16.5 years,
      mean 7.5) referred for non-scrotal testis, the number of high scrotal testis was
      prospectively determined. According to previous testis position, the high scrotal
      testis was classified into congenital- and acquired-high scrotal testis. In
      congenital-high scrotal testis orchidopexy was performed whereas spontaneous
      descent at puberty was awaited in acquired-high scrotal testis. In 210 testes,
      the gonad was diagnosed as high scrotal. In six testes the condition was
      congenital and 204 testes were diagnosed as acquired. All cases of congenital
      high scrotal testis were treated surgically. In 100 acquired-high scrotal testis
      follow-up was performed. Of these, 75 testes descended spontaneously at puberty.
      CONCLUSION: We propose that the high scrotal testis should be regarded, not as a
      distinct and separate entity, but as a part of the spectrum of either congenital
      undescended testis or acquired-undescended testis. Since spontaneous descent can
      occur at puberty in acquired-high scrotal testis, therapy may be different
      between both forms.

PMID- 16896646
TI  - Prevalence of lipodystrophy in HIV-infected children: a cross-sectional study.
AB  - OBJECTIVE: The aim of this study was to assess the changes in body fat
      distribution and lipid abnormalities in a population of HIV-infected children and
      adolescents followed in one single centre who had been exposed, or not, to
      antiretroviral therapy (ART). MATERIALS AND METHODS: Patients aged between 3 and
      19 years were evaluated in a cross-sectional study carried out between October
      and December 2002. Fat redistribution was evaluated independently by the
      physician and the patient. Fasting blood lipid profile, glucose, insulin and C
      peptide were measured. Among the 88 patients evaluated, 74 were taking ART.
      RESULTS: Fat redistribution was present in 20 patients, metabolic alterations
      alone were found in 22 children and 46 children had neither physical nor
      metabolic abnormalities. Patients with fat redistribution were found to have been
      on ART for a significantly longer period of time, with 42% of the children
      showing fat redistribution having been treated with antiretroviral agents for
      more than 5 years. These children had also been exposed to a higher number of
      antiretroviral agents. In contrast, metabolic alterations in the absence of fat
      redistribution were not related to the duration of ART nor to the number of drugs
      received. Treatment with stavudine or protease inhibitors was significantly
      associated with the presence of physical changes. CONCLUSION: Regular assessment
      of fat redistribution and metabolic markers should be carried out in children
      treated with antiretroviral agents and taken into account when adapting therapy
      during the long-term follow up of these children.

PMID- 16896647
TI  - Maternal perceptions of her child's body weight in infancy and early childhood
      and their relation to body weight status at age 7.
AB  - INTRODUCTION: Maternal perception of her child's weight status has been
      hypothesised to affect a child's weight development. OBJECTIVE: The aim of this
      analysis was to determine in how far the maternal weight perception of her
      child's weight at different ages is related to its future body weight status.
      MATERIALS AND METHODS: Longitudinal data on body weight, height and skinfolds
      from the Dortmund Nutritional and Anthropometric Longitudinally Designed Study
      were used to determine the risk of being overweight at age 7. Complete data on
      anthropometry, maternal weight perception and confounding variables were
      available for 253 children. RESULTS AND DISCUSSION: Maternal weight perception
      assessments at age 6 months, 12 months, 2 years and 4 years of age were related
      to body weight status as well as changes in body mass index standard deviation
      score (BMI-SDS) and skinfold SDS between age at assessment and age 7. With
      respect to the risk of being overweight at age 7, no independent effect of
      maternal perception was found. When changes in anthropometric measures were
      considered, it could be observed that children whose weight was considered too
      low gained more weight until age 7, and those who were considered to be too heavy
      lost more weight as compared to the children whose weight was considered to be
      just right. Among infants aged 6 months who were above the 85th percentile,
      maternal misperception appeared to promote an unfavourable weight development.
      These latter results support the hypothesis that maternal weight perception might
      affect a child's weight development. CONCLUSION: As our data suggest, this effect
      might begin to operate already in infancy.

PMID- 16896648
TI  - Growth hormone impaired secretion and antipituitary antibodies in patients with
      coeliac disease and poor catch-up growth after a long gluten-free diet period: a
      causal association?
AB  - INTRODUCTION: Coeliac disease (CD) is usually associated with impaired growth in
      children. A gluten-free diet (GFD) induces a catch-up growth with the recovery of
      height in about 2 years. AIM AND DISCUSSION: The lack of the height improvement
      has been related to growth hormone (GH) secretion impairment. CD is an autoimmune
      disease often associated with other endocrine and non-endocrine autoimmune
      disease. The aim of this study was to evaluate antipituitary autoantibodies (APA)
      and antihypothalamus autoantibodies in CD children with poor clinical response to
      a GFD and growth hormone deficiency (GHD). We diagnosed CD on the basis of
      specific antibodies and endoscopic biopsies in 130 patients aged 1-15 years.
      Seven CD children, without catch-up growth after at least 12-months GFD, were
      tested for GH secretion and, in five out of seven patients, the diagnosis of GHD
      was made in the absence of metabolic and systemic diseases. RESULTS: APA and
      antihypothalamus antibodies were detected by the indirect immunofluorescence
      method in the seven CD children without catch-up growth factor and in 25 CD
      children without growth impairment matched for sex and age, and in 58 healthy
      children as control groups. APA resulted positive at high titres in four out of
      five CD-GHD patients and were also positive at low titres (<1:8) in three of only
      CD children and in two out of 58 controls. Hypothalamic-pituitary magnetic
      resonance imaging (MRI) was normal in all patients except in one with cystic
      pineal. APA have been previously detected not only in adults with GHD, but also
      in idiopathic GHD children, suggesting the occurrence of an autoimmune
      hypophysitis in these patients. CONCLUSION: In our study, the presence of APA in
      CD children without catch-up growth after GFD seems to be able to identify an
      autoimmune form of hypophysitis involving the somatotrophs cells.

PMID- 16896649
TI  - Usefulness of Toxoplasma gondii recombinant antigens (GRA1, GRA7 and SAG1) in an
      immunoglobulin G avidity test for the serodiagnosis of toxoplasmosis.
AB  - The precise diagnosis of an acute and recent Toxoplasma infection in pregnant
      women and the newborn child is important before treatment. This study describes a
      new Toxoplasma gondii IgG avidity test based on a combination of recombinant
      GRA1, GRA7 and SAG1 antigens and shows that this test is useful for diagnostic
      purposes and may replace the lysed, whole-cell antigens. Although more sera need
      to be tested, the results obtained here suggest that the IgG avidity test
      performed with rec-antigens correlated more with the stage of a T. gondii
      infection than the IgG avidity results obtained with the lysed, whole-cell
      antigen test, the VIDAS Toxo IgG avidity (bioMerieux).

PMID- 16896650
TI  - Quantitative assessment of viable Cryptosporidium parvum load in commercial
      oysters (Crassostrea virginica) in the Chesapeake Bay.
AB  - The epidemiological importance of increasing reports worldwide on Cryptosporidium
      contamination of oysters remains unknown in relation to foodborne
      cryptosporidiosis. Thirty market-size oysters (Crassostrea virginica), collected
      from each of 53 commercial harvesting sites in Chesapeake Bay, MD, were
      quantitatively tested in groups of six for Cryptosporidium sp. oocysts by
      immunofluorescent antibody (IFA). After IFA analysis, the samples were
      retrospectively retested for viable Cryptosporidium parvum oocysts by combined
      fluorescent in situ hybridization (FISH) and IFA. The mean cumulative numbers of
      Cryptosporidium sp. oocysts in six oysters (overall, 42.1+/-4.1) were
      significantly higher than in the numbers of viable C. parvum oocysts (overall,
      28.0+/-2.9). Of 265 oyster groups, 221 (83.4%) contained viable C. parvum
      oocysts, and overall, from 10-32% (mean, 23%) of the total viable oocysts were
      identified in the hemolymph as distinct from gill washings. The amount of viable
      C. parvum oocysts was not related to oyster size or to the level of fecal
      coliforms at the sampling site. This study demonstrated that, although oysters
      are frequently contaminated with oocysts, the levels of viable oocysts may be too
      low to cause infection in healthy individuals. FISH assay for identification can
      be retrospectively applied to properly stored samples.

PMID- 16896651
TI  - Effectiveness of Zanthoxylum piperitum-derived essential oil as an alternative
      repellent under laboratory and field applications.
AB  - Recently, there were considerable efforts made to promote the use of
      environmentally friendly and biodegradable natural insecticides and repellents,
      particularly from botanical sources. In this study, Zanthoxylum piperitum-derived
      essential oil isolated by steam distillation was investigated and compared to the
      standard synthetic repellent, N,N-diethyl-3-methylbenzamide (DEET), for
      repellency against mosquitoes under laboratory and field conditions. The oil of
      Z. piperitum alone and also with 5% vanillin added repelled laboratory-reared
      female Aedes aegypti with the median protection times of 1.5 and 2.5 h,
      respectively. These repellency times were proven to be significantly lower than
      those of DEET-based products: 25% DEET and 25% DEET + 5% vanillin demonstrating
      3.5 and 5.5 h, respectively. However, when applied under field conditions, Z.
      piperitum oil + 5% vanillin was found to provide better protection against a wide
      range of natural mosquito populations than 25% DEET + 5% vanillin. While the
      product of DEET was effective in reducing bites with 99.7% protection, the
      protective effect of Z. piperitum oil product appeared complete (100%). It had a
      protective effect against Aedes gardnerii, Anopheles barbirostris, Armigeres
      subalbatus, Culex tritaeniorhynchus, Culex gelidus, Culex vishnui group, and
      Mansonia uniformis. The better repellency against a wide range of field
      mosquitoes derived from Z. piperitum oil products suggested an advantage of
      efficacy by providing a broad spectrum of activity. Therefore, Z. piperitum could
      have potential for use in the development of combined repellents as a natural
      active ingredient, synergist, or additive to conventional synthetic chemicals,
      particularly in situations when DEET is ineffective and impractical.

PMID- 16896652
TI  - Molecular characterization of a Theileria lestoquardi gene encoding for
      immunogenic protein splice variants.
AB  - A Theileria lestoquardi schizont cDNA library was screened using sera collected
      from sheep recovering from a natural malignant theileriosis infection. An
      immunogenic clone (clone-5) was isolated and its full sequence was obtained using
      rapid amplification of cDNA ends polymerase chain reaction (PCR) technique. PCR
      experiments and sequencing demonstrated the presence of two transcript forms of
      the gene, resulting from splicing variation at the single intron found in the
      gene. Both gene products, clone-5 long and clone-5 short variants with calculated
      molecular weights of 99.9 and 72.7 kDa, respectively, were expressed in a T.
      lestoquardi-infected cell line. BLAST searches suggested the presence of
      homologues of the gene in both the Theileria parva and Theileria annulata
      genomes, with identities of 53 and 62% on the DNA level, respectively. The intron
      was preserved in size, sequence, and location within the gene in these parasites.
      Analysis of the subcellular localization of the clone-5 proteins showed a
      predominant parasite membrane association in T. lestoquardi-infected cells. Both
      recombinantly produced forms were found to be reactive with sera from infected
      animals. Bioinformatic analyses were employed to address the possible function of
      the gene products in the biology of T. lestoquardi.

PMID- 16896653
TI  - Redescription of Trypanosoma ophiocephali Chen 1964 (Kinetoplastida:
      Trypanosomatina: Trypanosomatidae) and first record from the blood of dark
      sleeper (Odontobutis obscura Temminck and Schlegel) in China.
AB  - During the parasite fauna investigation within 2004 and 2005, the freshwater fish
      trypanosomes were isolated from the blood of dark sleeper (Odontobutis obscura
      Temminck and Schlegel) and snakehead fish (Ophiocephalus argus Cantor) from
      Niushan Lake, Hubei Province, China. Blood trypomastigotes were used for light
      microscopy investigations. The detailed descriptions of three morphological
      groups of the genus Trypanosoma: Trypanosoma sp. I and Trypanosoma sp. II found
      in blood of O. obscura, and Trypanosoma sp. III found in blood of O. argus were
      provided. Morphological features and host species show Trypanosoma sp. III belong
      to Trypanosoma ophiocephali Chen 1964, an incompletely described species.
      Infection with trypanosomes of O. obscura was recorded for the first time.
      According to the size and appearance, the trypanosomes in O. obscura were also
      tentatively identified as T. ophiocephali Chen 1964.

PMID- 16896654
TI  - Neuromusculature of Macrogyrodactylus congolensis, a monogenean skin parasite of
      the Nile catfish Clarias gariepinus.
AB  - Phalloidin fluorescence technique, enzyme cytochemistry and immunocytochemistry,
      in conjunction with confocal scanning laser microscopy, were used to describe the
      neuromusculature of the monogenean skin parasite Macrogyrodactylus congolensis
      from the Nile catfish Clarias gariepinus. The body wall muscles are composed of
      an outer layer of compactly arranged circular fibres, an intermediate layer of
      paired longitudinal fibres and an inner layer of well-spaced bands of diagonal
      fibres arranged in two crossed directions. The central nervous system consists of
      paired cerebral ganglia from which three pairs of longitudinal ventral, lateral
      and dorsal nerve cords arise. The nerve cords are connected at intervals by many
      transverse connectives. Both central and peripheral nervous systems are
      bilaterally symmetrical and better developed ventrally than laterally and
      dorsally. Structural and functional correlates of the neuromusculature of the
      pharynx, haptor and reproductive tracts were examined. Results implicate
      acetylcholine, FMRFamide-related peptides and serotonin in sensory and motor
      function. The results were compared with those of Macrogyrodactylus clarii, a
      gill parasite of the same host fish C. gariepinus.

PMID- 16896655
TI  - Fasciola hepatica: morphological effects of a combination of triclabendazole and
      clorsulon against mature fluke.
AB  - A study has been carried out to investigate the morphological effects of half
      strength triclabendazole (TCBZ), half-strength clorsulon, and a combination of
      these two drugs against mature Fasciola hepatica. The Cullompton TCBZ-susceptible
      isolate was used for these experiments. Flukes were incubated for 24 h in vitro
      in TCBZ sulphoxide (7.5 microg/ml), clorsulon (5 microg/ml), or a combination of
      the two drugs. For the in vivo experiment, rats were dosed with TCBZ (6.25 mg/kg
      body weight), clorsulon (5 mg/kg body weight), or a combination of the two drugs
      and flukes recovered after 48 h. Surface changes to the flukes were assessed by
      scanning electron microscopy. Treatment with the combination of drugs produced
      greater disruption to the flukes than the individual drugs at half-strength, both
      in vivo and in vitro. Disruption to the tegument of the flukes induced by the
      individual drugs at half-strength was relatively minor and less than that caused
      by the drugs at full-strength. The results suggest that there are additive
      effects between TCBZ and clorsulon, which may be indicative of synergy: the use
      of drug combinations would be of value in the treatment of triclabendazole
      resistant fluke.

PMID- 16896657
TI  - Aptamers and in-beam PET for advanced diagnosis and therapy optimisation.

PMID- 16896658
TI  - Is novelty leading us astray?

PMID- 16896656
TI  - Radionuclide imaging of spinal infections.
AB  - BACKGROUND: The diagnosis of spinal infection, with or without implants, has been
      a challenge for physicians for many years. Spinal infections are now being
      recognised more frequently, owing to aging of the population and the increasing
      use of spinal-fusion surgery. DISCUSSION: The diagnosis in many cases is delayed,
      and this may result in permanent neurological damage or even death. Laboratory
      evidence of infection is variable. Conventional radiography and radionuclide bone
      imaging lack both sensitivity and specificity. Neither in vitro labelled
      leucocyte scintigraphy nor 99mTc-anti-granulocyte antibody scintigraphy is
      especially useful, because of the frequency with which spinal infection presents
      as a non-specific photopenic area on these tests. Sequential bone/gallium imaging
      and 67Ga-SPECT are currently the radionuclide procedures of choice for spinal
      osteomyelitis, but these tests lack specificity, suffer from poor spatial
      resolution and require several days to complete. [18F]Fluoro-2-deoxy-D-glucose
      (FDG) PET is a promising technique for diagnosing spinal infection, and has
      several potential advantages over conventional radionuclide tests. RESULTS: The
      study is sensitive and is completed in a single session, and image quality is
      superior to that obtained with single-photon emitting tracers. The specificity of
      FDG-PET may also be superior to that of conventional tracers because degenerative
      bone disease and fractures usually do not produce intense FDG uptake; moreover,
      spinal implants do not affect FDG imaging. However, FDG-PET images have to be
      read with caution in patients with instrumented spinal-fusion surgery since non
      specific accumulation of FDG around the fusion material is not uncommon.
      CONCLUSION: In the future, PET-CT will likely provide more precise localisation
      of abnormalities. FDG-PET may prove to be useful for monitoring response to
      treatment in patients with spinal osteomyelitis. Other tracers for diagnosing
      spinal osteomyelitis are also under investigation, including radiolabelled
      antibiotics, such as 99mTc-ciprofloxacin, and radiolabelled streptavidin-biotin
      complex. Antimicrobial peptides display preferential binding to microorganisms
      over human cells and perhaps new radiopharmaceuticals will be recruited from the
      array of human antimicrobial peptides/proteins. In experiments with Tc
      ubiquicidin-derived peptides, radioactivity at the site of infection correlated
      well with the number of viable bacteria present. Finally, radiolabelled
      antifungal tracers could potentially distinguish fungal from bacterial
      infections.

PMID- 16896659
TI  - Homocysteine levels are associated with the results of 123I
      metaiodobenzylguanidine myocardial scintigraphy in type 2 diabetic patients.
AB  - PURPOSE: Elevated total plasma homocysteine (tHcy) levels and cardiovascular
      autonomic dysfunction are associated with a high mortality in type 2 diabetic
      patients. We tested the hypothesis that hyperhomocysteinemia is associated with
      insulin resistance and cardiovascular autonomic dysfunction in type 2 diabetic
      patients not receiving insulin treatment. METHODS: The study group consisted of
      17 type 2 diabetic patients with high tHcy levels (>15 mmol/l, age 58+/-5 years,
      high tHcy group). The control group consisted of 23 age-matched type 2 diabetic
      patients with normal tHcy levels (<or=15 mmol/l, age 58+/-9 years, normal tHcy
      group). Cardiovascular autonomic function was assessed by baroreflex sensitivity,
      heart rate variability, plasma norepinephrine concentrations, and cardiac (123)I
      metaiodobenzylguanidine (MIBG) scintigraphy. RESULTS: Early and delayed (123)I
      MIBG myocardial uptake values were lower (p<0.005 and p<0.01, respectively) and
      the percent washout rate of (123)I-MIBG was higher (p<0.001) in the high tHcy
      group than in the normal tHcy group. The fasting plasma insulin concentrations
      (p<0.0001) and the homeostasis model assessment (HOMA) index values (p<0.0001)
      were higher in the high tHcy group than in the normal tHcy group. Multiple
      regression analysis revealed that the level of tHcy was independently predicted
      by the HOMA index values and the myocardial uptake of (123)I-MIBG at the delayed
      phase. CONCLUSION: Our results demonstrate that high levels of tHcy are
      associated with depressed cardiovascular autonomic function and insulin
      resistance in patients with type 2 diabetes mellitus.

PMID- 16896660
TI  - Impact of staging with 18F-FDG-PET on outcome of patients with stage III non
      small cell lung cancer: PET identifies potential survivors.
AB  - PURPOSE: The aim of this study was to analyse the impact of FDG-PET staging on
      treatment results of neo-adjuvant radiochemotherapy in patients with advanced non
      small cell lung cancer (NSCLC). We compared prospectively the outcome of two
      patient groups with stage III NSCLC undergoing the same neo-adjuvant radio
      chemotherapy (NARCT). In one group, FDG-PET was part of the pretherapeutic
      staging, whereas in the other group, no PET scans were performed. METHODS: One
      hundred and eighty-eight patients with advanced stage III NSCLC were selected for
      a phase II trial of NARCT. The first 115 patients underwent conventional workup
      (CWU) and FDG-PET before inclusion (group I); the remaining 73 patients underwent
      CWU only (group II). All patients were followed up according to a standardised
      protocol for at least 11 months (up to 64 months). Overall survival and disease
      free survival were used as parameters of therapeutic success and analysed
      statistically. RESULTS: After staging, 157/188 patients were included in the
      clinical trial. Thirty-one were excluded owing to the results of FDG-PET, in most
      cases because of the detection of previously unknown distant metastases. Overall
      survival and metastasis-free survival were significantly longer in patients of
      group I stratified by FDG-PET than in group II (p=0.006 and 0.02 respectively).
      Another significant factor for survival was complete tumour resection (p=0.02).
      Gender, histological tumour type, tumour grade and UICC stage had no significant
      influence. CONCLUSION: Pretherapeutic staging by FDG-PET significantly influences
      the results of NARCT and subsequent surgery by identifying patients not eligible
      for curative treatment.

PMID- 16896661
TI  - Fusion imaging of computed tomographic pulmonary angiography and SPECT
      ventilation/perfusion scintigraphy: initial experience and potential benefit.
AB  - PURPOSE: The objective of this study was to examine the feasibility of fusing
      ventilation and perfusion data from single-photon emission computed tomography
      (SPECT) ventilation perfusion (V/Q) scintigraphy together with computed
      tomographic pulmonary angiography (CTPA) data. We sought to determine the
      accuracy of this fusion process. In addition, we correlated the findings of this
      technique with the final clinical diagnosis. METHODS: Thirty consecutive patients
      (17 female, 13 male) who had undergone both CTPA and SPECT V/Q scintigraphy
      during their admission for investigation of potential pulmonary embolism were
      identified retrospectively. Image datasets from these two modalities were co
      registered and fused using commercial software. Accuracy of the fusion process
      was determined subjectively by correlation between modalities of the anatomical
      boundaries and co-existent pleuro-parenchymal abnormalities. RESULTS: In all 30
      cases, SPECT V/Q images were accurately fused with CTPA images. An automated
      registration algorithm was sufficient alone in 23 cases (77%). Additional linear
      z-axis scaling was applied in seven cases. There was accurate topographical co
      localisation of vascular, parenchymal and pleural disease on the fused images.
      Nine patients who had positive CTPA performed as an initial investigation had co
      localised perfusion defects on the subsequent fused CTPA/SPECT images. Three of
      the 11 V/Q scans initially reported as intermediate could be reinterpreted as low
      probability owing to co-localisation of defects with parenchymal or pleural
      pathology. CONCLUSION: Accurate fusion of SPECT V/Q scintigraphy to CTPA images
      is possible. This technique may be clinically useful in patients who have non
      diagnostic initial investigations or in whom corroborative imaging is sought.

PMID- 16896662
TI  - Can the detection of misery perfusion in chronic cerebrovascular disease be based
      on reductions in baseline CBF and vasoreactivity?
AB  - PURPOSE: The aim of this study was to clarify whether decreases in baseline
      regional cerebral blood flow (rCBF) and in residual cerebral vasoreactivity
      (CVR), assessed by the acetazolamide (ACZ) challenge, can detect misery perfusion
      in patients with chronic cerebrovascular disease (CVD). METHODS: Oxygen
      extraction fraction (OEF) and other haemodynamic parameters were measured in 115
      patients (64+/-9 years old) with unilateral cerebrovascular steno-occlusive
      disease (>70% stenosis) using (15)O-gas and water PET. A significant elevation of
      OEF, by greater than the mean+2SD compared with healthy controls, was defined as
      misery perfusion. CBF, CVR determined by percent change in CBF after ACZ
      administration, OEF and other haemodynamic parameters in the territories of the
      bilateral middle cerebral arteries were analysed. Diagnostic accuracy for the
      detection of misery perfusion using the criteria determined by baseline CBF and
      CVR was evaluated in all patients and in only those patients with occlusive
      lesions. RESULTS: Ten of 24 patients with misery perfusion showed a significant
      reduction in CVR. Using criteria determined by significant decreases in CVR and
      baseline CBF, misery perfusion was detected with a sensitivity of 42% and a
      specificity of 95% in all patients. In patients with occlusive lesions (n=50),
      sensitivity was higher but specificity was slightly lower. The diagnostic
      accuracy of the threshold determined by baseline CBF alone was similar in all
      patients and in only those patients with occlusive lesions, and was higher than
      that achieved using the asymmetry index of OEF. CONCLUSION: Reductions in CVR and
      baseline CBF in the ACZ challenge for CVD would detect misery perfusion with high
      specificity. Reduction in baseline rCBF is more accurate than reduction in CVR
      alone for the detection of misery perfusion.

PMID- 16896664
TI  - Low dose non-enhanced CT versus standard dose contrast-enhanced CT in combined
      PET/CT protocols for staging and therapy planning in non-small cell lung cancer.
AB  - PURPOSE: To evaluate low dose non-enhanced CT and standard dose contrast-enhanced
      CT in combined PET/CT protocols for staging and therapy planning of non-small
      cell lung cancer (NSCLC). METHODS: Retrospective analysis was performed of 50
      consecutive patients with proven NSCLC who had been referred for primary staging
      (n=41) or restaging (n=9). All patients underwent a multi-phase PET/CT consisting
      of a low dose non-enhanced attenuation scan and an arterial and portal-venous
      contrast-enhanced CT scan followed by whole-body PET. Fused datasets of non
      enhanced and contrast-enhanced PET/CT were compared per patient by using the TNM
      staging system, and per lesion regarding localisation, characterisation and
      delineation of tumour lesions. The staging results were validated either by
      histopathology or by clinical-radiological follow-up for >or=6 months. RESULTS:
      In 47/50 patients, the results of T staging did not differ between the two PET/CT
      protocols. Three patients could only be correctly classified as having T4 tumours
      after contrast application. Regarding N staging, both protocols yielded the same
      results. In M staging, there was only one patient with an improvement of the
      results as a result of contrast application. The lesion-based analysis of 92
      sites showed no difference in the accuracy of lesion localisation and only one
      revision of lesion characterisation by contrast-enhanced PET/CT. The assessment
      of tumour delineation was altered by contrast application in 58/92 sites
      (p<0.0001). In 10/50 patients, contrast-enhanced PET/CT detected additional
      clinically important findings. CONCLUSION: In patients with advanced NSCLC,
      contrast-enhanced CT as part of the PET/CT protocol more accurately assessed the
      TNM stage in 8% of patients compared with non-contrast PET/CT. However, for
      planning of 3D conformal radiotherapy and non-conventional surgery, contrast
      enhanced PET/CT protocols are indispensable owing to their superiority in
      precisely defining the tumour extent.

PMID- 16896663
TI  - Auger radiation targeted into DNA: a therapy perspective.
AB  - BACKGROUND: Auger electron emitters that can be targeted into DNA of tumour cells
      represent an attractive systemic radiation therapy goal. In the situation of DNA
      associated decay, the high linear energy transfer (LET) of Auger electrons gives
      a high relative biological efficacy similar to that of alpha particles. In
      contrast to alpha radiation, however, Auger radiation is of low toxicity when
      decaying outside the cell nucleus, as in cytoplasm or outside cells during blood
      transport. The challenge for such therapies is the requirement to target a high
      percentage of all cancer cells. An overview of Auger radiation therapy approaches
      of the past decade shows several research directions and various targeting
      vehicles. The latter include hormones, peptides, halogenated nucleotides,
      oligonucleotides and internalising antibodies. DISCUSSION: Here, we will discuss
      the basic principles of Auger electron therapy as compared with vector-guided
      alpha and beta radiation. We also review some radioprotection issues and briefly
      present the main advantages and disadvantages of the different targeting
      modalities that are under investigation.

PMID- 16896665
TI  - Incidental finding of an (11)C-choline PET-positive solitary plasmacytoma lesion.

PMID- 16896666
TI  - Imaging the neurobiological substrate of atypical depression by SPECT.
AB  - PURPOSE: Neurobiological abnormalities underlying atypical depression have
      previously been suggested. The purpose of this study was to explore differences
      at functional brain imaging between depressed patients with and without atypical
      features and healthy controls. METHODS: Twenty-three out-patients with chronic
      depressive disorder recruited from a service for patients with audiological
      symptoms were investigated. Eleven fulfilled the DSM-IV criteria for atypical
      depression (mood reactivity and at least two of the following: weight gain,
      hypersomnia, leaden paralysis and interpersonal rejection sensitivity). Twenty
      three healthy subjects served as controls. Voxel-based analysis was applied to
      explore differences in (99m)Tc-HMPAO uptake between groups. RESULTS: Patients in
      the atypical group had a higher prevalence of bilateral hearing impairment and
      higher depression and somatic distress ratings at the time of SPECT.
      Significantly higher tracer uptake was found bilaterally in the atypical group as
      compared with the non-atypicals in the sensorimotor (Brodmann areas, BA1-3) and
      premotor cortex in the superior frontal gyri (BA6), in the middle frontal cortex
      (BA8), in the parietal associative cortex (BA5, BA7) and in the inferior parietal
      lobule (BA40). Significantly lower tracer distribution was found in the right
      hemisphere in the non-atypicals compared with the controls in BA6, BA8, BA44,
      BA45 and BA46 in the frontal cortex, in the orbito-frontal cortex (BA11, BA47),
      in the postcentral parietal cortex (BA2) and in the multimodal association
      parietal cortex (BA40). CONCLUSION: The differences found between atypical and
      non-atypical depressed patients suggest different neurobiological substrates in
      these patient groups. The putative links with the clinical features of atypical
      depression are discussed. These findings encourage the use of functional
      neuroimaging in psychiatric disorders.

PMID- 16896667
TI  - Use of coronary calcium score scans from stand-alone multislice computed
      tomography for attenuation correction of myocardial perfusion SPECT.
AB  - PURPOSE: To evaluate the use of CT attenuation maps, generated from coronary
      calcium scoring (CCS) scans at in- and expiration with a 64-slice CT scanner, for
      attenuation correction (AC) of myocardial perfusion SPECT images. METHODS: Thirty
      two consecutive patients underwent( 99m)Tc-tetrofosmin gated adenosine
      stress/rest SPECT scan on an Infinia Hawkeye SPECT-CT device (GE Medical Systems)
      followed by CCS and CT angiography on a 64-slice CT. AC of the iteratively
      reconstructed images was performed with AC maps obtained: (a) from the "Hawkeye"
      low-resolution X-ray CT facility attached to the Infinia camera (IRAC); (b) from
      the CCS scan acquired on a 64-slice CT scanner during maximal inspiration
      (AC(INSP)) and (c) during normal expiration (AC(EXP)). Automatically determined
      uptake values of stress scans (QPS, Cedars Medical Sinai) from AC(INSP) and
      AC(EXP) were compared with IRAC. Agatston score (AS) values using AC(INSP)versus
      AC(EXP) were also compared. RESULTS: AC(INSP) and AC(EXP) resulted in identical
      findings versus IRAC by visual analysis. A good correlation for uptake values
      between IRAC and AC(INSP) was found (apex, r=0.92; anterior, r=0.85; septal,
      r=0.91; lateral, r=0.86; inferior, r=0.90; all p<0.0001). The correlation was
      even closer between IRAC and AC(EXP) (apex, r=0.97; anterior, r=0.91; septal,
      r=0.94; lateral, r=0.92; inferior, r=0.97; all p<0.0001). The mean AS during
      inspiration (319+/-737) and expiration(317+/-778) was comparable (p=NS).
      CONCLUSION: Attenuation maps from CCS allow accurate AC of SPECT MPI images.
      AC(EXP) proved superior to AC(INSP), suggesting that in hybrid scans CCS may be
      performed during normal expiration to allow its additional use for AC of SPECT
      MPI.

PMID- 16896668
TI  - Reproducibility of [123I]PE2I binding to dopamine transporters with SPECT.
AB  - PURPOSE: The iodinated cocaine derivative [(123)I]PE2I is a new selective ligand
      for in vivo studies of the dopamine transporter (DAT) with SPECT. Recently, a
      bolus/infusion (B/I) protocol for [(123)I]PE2I measurements of DAT density was
      established [Pinborg LH et al. J Nucl Med 2005;46:1119-271]. The aims of this
      study were, firstly, to evaluate the test-retest variability using the B/I
      protocol and, secondly, to evaluate the B/I approach in a new group of healthy
      subjects using two outcome parameters, BP(1) (C(ROI)/C(plasma)) and BP(2)
      (C(ROI)/C(REF)). METHODS: Seven healthy subjects were subjected to [(123)I]PE2I
      SPECT scanning twice. For both studies, the two outcome parameters BP(1) and
      BP(2) were calculated based on two different methods for region of interest (ROI)
      delineation, namely manual delineation and probability map-based automatic
      delineation with MRI co-registration. RESULTS: With manual delineation, striatal
      test-retest variability (absolute difference between first and second scan as a
      percentage of the mean) of BP(1) and BP(2) was 13.9% (range 1.8-35.7%) and 4.1%
      (range 0.5-9.7%) respectively. The probability map-based automatic delineation
      resulted in striatal test-retest variability of 17.2% (range 4.3-40.5%) and 5.2%
      (range 0.1-10.9%) respectively. The B/I approach provided stable brain activity
      from 120 to 180 min post injection in both high- and low-count regions with a
      mean % change/hour in striatal BP(2) of 10.6. CONCLUSION: [(123)I]PE2I SPECT with
      the B/I approach yields a highly reproducible measure of striatal dopamine
      transporter binding. The appropriateness of a B/I protocol with a B/I ratio of
      2.7 h (i.e. with a bolus worth 2.7 h of infusion) was confirmed in an independent
      sample of healthy subjects.

PMID- 16896669
TI  - Uptake of 4-borono-2-[18F]fluoro-L-phenylalanine in sporadic and
      neurofibromatosis 2-related schwannoma and meningioma studied with PET.
AB  - PURPOSE: Meningiomas and schwannomas associated with neurofibromatosis 2 (NF2)
      are difficult to control by microsurgery and stereotactic radiotherapy alone.
      Boron neutron capture therapy (BNCT) is a chemically targeted form of
      radiotherapy requiring increased concentration of boron-10 in tumour tissue. PET
      with the boron carrier 4-borono-2-[(18)F]fluoro-L-phenylalanine ([(18)F]FBPA)
      allows investigation of whether 4-borono-L-phenylalanine (BPA) concentrates in
      NF2 tumours, which would make BNCT feasible. METHODS: We studied dynamic uptake
      of [(18)F]FBPA in intracranial meningiomas (n=4) and schwannomas (n=6) of five
      sporadic and five NF2 patients. Tracer input function and cerebral blood volume
      were measured. [(18)F]FBPA uptake in tumour and brain was assessed with a three
      compartmental model and graphical analysis. These, together with standardised
      uptake values (SUVs), were used to define tumour-to-brain [(18)F]FBPA tissue
      activity gradients. RESULTS: Model fits with three parameters K (1) (transport),
      k (2) (reverse transport) and k (3) (intracellular metabolism) were found to best
      illustrate [(18)F]FBPA uptake kinetics. Maximum SUV was two- to fourfold higher
      in tumour as compared with normal brain and independent of NF2 status. The
      increased uptake was due to higher transport of [(18)F]FBPA in tumour. In
      multiple-time graphical analysis (MTGA, Gjedde-Patlak plot) the tumour-to-brain
      [(18)F]FBPA influx constant (K (i) -MTGA) ratios varied between 1.8 and 5.4 in
      NF2-associated tumours while in sporadic tumours the ratio was 1-1.4. CONCLUSION:
      [(18)F]FBPA PET offers a viable means to evaluate BPA uptake in meningiomas and
      schwannomas in NF2. Based on our results on tumour uptake of [(18)F]FBPA, some of
      these benign neoplasms may be amenable to BNCT.

PMID- 16896670
TI  - Diagnostic value of kinetic analysis using dynamic FDG PET in immunocompetent
      patients with primary CNS lymphoma.
AB  - PURPOSE: The purpose of this study was to investigate the accumulation of FDG in
      immunocompetent patients with primary central nervous system (CNS) lymphoma using
      qualitative and quantitative PET images and to compare baseline with follow-up
      PET after therapy. METHODS: Twelve immunocompetent patients with CNS lymphoma
      were examined. Dynamic emission data were acquired for 60 min immediately
      following injection of FDG. In seven patients, repeated PET studies were
      performed after treatment. Applying a three-compartment five-parameter model, K
      (1), k (2), k (3), k (4), vascular fraction (V ( B )) and cerebral metabolic rate
      of glucose (CMR(Glc)) were obtained. We evaluated the FDG uptake visually using
      qualitative and parametric images and quantitatively using parametric images.
      RESULTS: A total of 12 lesions were identified in ten patients with newly
      diagnosed CNS lymphoma. On visual analysis, ten lesions showed an increase on
      qualitative images, eight showed an increase on K (1) images, 12 showed an
      increase on k (3) images and ten showed an increase on CMR(Glc) images. On
      quantitative analysis, k (2), k (3) and CMR(Glc) values of the lesion were
      significantly different from those of the normal grey matter (p<0.02-0.0005). A
      total of three lesions were identified in two patients with recurrent tumour. All
      three lesions showed an increase on qualitative, k (3) and CMR(Glc) images. The K
      (1), k (2), k (3) and CMR(Glc) values after treatment were significantly
      different from those obtained before treatment (p<0.04-0.008). CONCLUSION:
      Kinetic analysis, especially with respect to k (3), using dynamic FDG PET might
      be helpful for diagnosis of CNS lymphoma and for monitoring therapeutic
      assessment.

PMID- 16896671
TI  - Predictive value of 99mTc-sestamibi scintigraphy for healing of extremity
      amputation.
AB  - PURPOSE: Although various non-invasive procedures have been proposed to determine
      the optimal level of amputation of limbs in patients who have vascular disease,
      currently there are no consistent criteria that can be applied before surgery.
      The purpose of this study was to determine whether (99m)Tc-sestamibi imaging can
      accurately predict the healing of amputation sites. METHODS: In a prospective
      study in 26 patients (21 men, 5 women; age range 23-94 years) presenting with
      ulcers or gangrene of the foot and hand, (99m)Tc-sestamibi imaging was performed
      preoperatively. The indications for amputation included gangrene (23 patients),
      electrical injury (2 patients) and trauma (1 patient) of extremities. Although
      the amputation levels were chosen according to clinical criteria and
      scintigraphic results, the final amputation level was defined by scintigraphic
      results. Two below-knee, one above-knee, 12 toe, 11 transmetatarsal, two phalanx,
      one finger and one thumb amputations and one shoulder disarticulation were
      performed. In four cases, the amputation defect was not suitable for coverage
      using a local dermal flap; rather, it was covered with free tissue transfer.
      Patients had clinical follow-up for 6-36 months (mean 11.69 months) to assess
      healing of the stump. Scan results were compared with clinical outcome to assess
      prediction of healing. RESULTS: There was healing in all amputations at the end
      of the follow-up period. When evaluated regarding preoperative (99m)Tc-sestamibi
      uptake pattern, there was no perfusion to the lesion site in 21 patients and
      perfusion to an area smaller than the extent of skin necrosis in four patients;
      thus, in these 25 patients, (99m)Tc-sestamibi scintigraphy suggested non-viable
      tissue in the extremities with clear-cut edges of perfused muscle tissue.
      Diffusely decreased uptake was seen below the left knee in one case. How
      scintigraphy changed management was analysed. The amputation levels proposed
      before scintigraphy were divided into two groups, "definite" (n=14) and
      "indefinite" (n=12), based on visual examination and Doppler findings. In nine
      patients in the definite group, the proposed amputation level before scintigraphy
      was not altered by the scintigraphic data. However, (99m)Tc-sestamibi scan
      enabled unnecessarily high amputation levels to be avoided in 12 patients in the
      indefinite group and in five patients in the definite group. Therefore, there was
      change in management of 65% of cases based on scintigraphic findings. CONCLUSION:
      Since healing of the stump was seen in all cases, outcome was correctly predicted
      by scintigraphy. This preliminary study supports the use of (99m)Tc-sestamibi
      scan in selecting the optimal amputation level consistent with subsequent stump
      healing.

PMID- 16896672
TI  - Successful high-resolution animal positron emission tomography of human Ewing
      tumours and their metastases in a murine xenograft model.
AB  - PURPOSE: As primary osseous metastasis is the main adverse prognostic factor in
      patients with Ewing tumours, a NOD/scid mouse model for human Ewing tumour
      metastases has been established to examine the mechanisms of metastasis. The aim
      of this study was to evaluate the feasibility of diagnostic molecular imaging by
      small animal PET in this mouse model. METHODS: Human Ewing tumour cells were
      transplanted into immune-deficient NOD/scid mice via s.c injection (n=17) or i.v.
      injection (n=17). The animals (mean weight 23.2 g) were studied 2-7 weeks after
      transplantation using a submillimetre resolution animal PET scanner. To assess
      glucose utilisation and bone metabolism, mice were scanned after intravenous
      injection of 9.6 MBq (mean) 2-[(18)F]fluoro-2-deoxy-D: -glucose (FDG) or 9.4 MBq
      (mean) [(18)F]fluoride. Whole-body PET images were analysed visually and semi
      quantitatively [%ID/g, tumour to non-tumour ratio (T/NT)]. Foci of pathological
      uptake were identified with respect to the physiological organ uptake in
      corresponding regions. RESULTS: Subcutaneously transplanted Ewing tumours
      demonstrated a moderately increased glucose uptake (median %ID/g 2.5; median T/NT
      2.2). After i.v. transplantation, the pattern of metastasis was similar to that
      in patients with metastases in lung, bone and soft tissue. These metastases
      showed an increased FDG uptake (median %ID/g 3.6; median T/NT 2.7). Osseous
      metastases were additionally visible on [(18)F]fluoride PET by virtue of
      decreased [(18)F]fluoride uptake (osteolysis; median %ID/g 8.4; median T/NT
      0.59). Metastases were confirmed immunohistologically. CONCLUSION: Diagnostic
      molecular imaging of Ewing tumours and their small metastases in an in vivo
      NOD/scid mouse model is feasible using a submillimetre resolution PET scanner.

PMID- 16896673
TI  - [Concepts and problems of lobular neoplasia].
AB  - The term lobular neoplasia (LN) includes lobular carcinoma in situ (LCIS) and
      atypical lobular neoplasia (ALH). It is generally considered to be a risk lesion
      and a non-obligatory precursor for the subsequent development of an invasive
      carcinoma in the ipsilateral or contralateral breast. LN has also been termed
      lobular intraepithelial neoplasia (LIN). A grading system (LIN 1-LIN 3) has been
      suggested as a tool for a more precise estimation of the individual risk. When LN
      is the most significant finding in a core biopsy, the probability of a higher
      grade lesion is about 17% in the follow-up surgical biopsy, justifying follow-up
      surgery in the majority of cases. A higher risk of progression is attributed to
      LIN 3 (pleomorphic LN, extensive LN, and signet ring cell LN) compared to LIN 1
      or LIN 2. These special forms of LN may have an unusual presentation clinically
      or histologically. Using immunohistology, LN are characterized by the loss of E
      cadherin, low proliferative activity and by positive hormone receptor status. The
      molecular characteristics of LN are similar to those of invasive lobular
      carcinomas, indicating the nature of LN as a precursor lesion.

PMID- 16896674
TI  - [The significance of "normal tissue" in the development of breast cancer: new
      concepts of early carcinogenesis].
AB  - Only little information on the primary molecularbiological events involved in
      early breast is available. In particular, the definition of postulated precursor
      lesions of invasive breast cancer, such as ductal hyperplasia or ductal carcinoma
      in situ, is under an intense, controversial discussion in terms of pathogenesis
      and tumor biology. The most recent research on biological regulation mechanisms
      and genetic alterations in morphologically normally appearing breast tissue give
      rise for a reinterpretation for the most common progression models of breast
      cancer. The detection of genetic alterations within normal breast tissue in
      particular challenges the commonly postulated relationship between invasive and
      in situ breast carcinomas on the one hand, and benign, proliferative breast
      lesions on the other. The concerns about these relationship are further supported
      by the description of different cellular compartments within the normal female
      breast, including a "progenitor cell compartment" with different cytokeratin
      expression patterns, which can be transferred towards well known or suspected
      precursor lesions of invasive and in situ breast cancer. The aim of this
      manuscript is to provide an overview of the most recent results and developments
      in breast pathology, and to describe the consequences of our changing
      understanding of breast carcinogenesis.

PMID- 16896675
TI  - [Improvement of breast cancer grading in punch biopsies: grading with the Ki-67
      marker].
AB  - The grading of invasive breast cancers according to Bloom and Richardson
      (Nottingham modification) provides one of the most important prognostic factors
      in addition to size and the status of the lymph nodes. Diagnostic reproducibility
      has been problematic in daily practice as the required criteria for selection and
      extent of the grading area are frequently not present in the punch biopsies.A
      total of 346 cases were retrospectively used to compare routine grading from
      surgical preparations with an equivalently small sample from punch biopsies. In
      addition, a modified grading of these small samples was developed with Ki-67
      immunochemistry and the measurement of core size. In the case of modified
      grading, 1-3 points were given for Ki-67 and average maximum core diameter.
      Tubule development was evaluated with 1 or 2 points. A comparison for recurrence
      free survival and total survival showed significant prognostic differences
      between 3-5 points (low risk) and 6-8 points (high risk) in uni- and multivariate
      analyses. The evaluation criteria for Nottingham-Bloom-Richardson grading in a
      small tissue sample, such as that from a punch biopsy, can hardly be fulfilled.
      In our series, prognostic value was only found for nodal negative cases. After
      modification using objective parameters such as nuclear size measurement and Ki
      67 proliferation index, a small tissue sample can prove to be of significant
      prognostic value for nodal negative as well as nodal positive cases.

PMID- 16896677
TI  - [Salivary gland-like tumors of the breast].
AB  - A subset of rare benign and malignant breast tumors with and without
      myoepithelial differentiation are morphologically and histogenetically similar to
      salivary gland tumors, but may differ in incidence and clinical behavior. The
      clinicopathological, immunohistochemical, molecular and prognostic features of
      ten salivary gland-like tumor entities of the breast are discussed and compared
      with their respective counterparts in the salivary glands.

PMID- 16896676
TI  - [Prognostic factors in ductal carcinoma in situ].
AB  - Ductal carcinoma in situ (DCIS) is a heterogeneous disease that progresses to
      invasive cancer in 30-50% of the patients. Its natural history is poorly defined
      so that we are unable to identify cases of DCIS that do not progress to invasive
      carcinoma during an individual's lifetime. However, pathologic features of DCIS
      are nowadays the basis for the estimation of the prognosis and planning of
      therapy. Exclusion of microinvasion, characterization of nuclear grade,
      architecture, size and distribution of the DCIS, presence or absence of
      comedonecrosis as well as the assessment of surgical margins are relevant factors
      for local treatment. The determination of steroid hormone receptor status is
      indicated in patients considering tamoxifen therapy after breast conservation. It
      is advisable to evaluate the features according to internationally accepted
      guidelines with proven prognostic relevance and reproducibility. Nevertheless,
      better prognostic factors are needed to adapt the management of this increasingly
      diagnosed disease to the individual patient.

PMID- 16896678
TI  - [Papillary tumors of the breast].
AB  - The term papilloma applies to benign proliferative epithelial breast lesions with
      a papillary architecture. The papillae in such lesions contain an arborizing
      fibrovascular core, glandular surface epithelium and a basal myoepithelial layer.
      A basement membrane encloses these structures. Papilloma may occur at any site in
      the ductal lobular system and according to its localization is subdivided into
      two types: solitary (central) papilloma which are located in the major
      nipple/subareolar ducts or large segmental ducts and multiple (peripheral)
      papillomas in cystically dilated terminal ductal lobular units (TDLU). Stromal
      changes, epithelial metaplasia and/or proliferations and neoplasia may alter the
      prototypical architecture. In a significant number of papillomas atypia can be
      identified which have to be classified as atypical proliferates of the ductal
      type. These lesions must be distinguished from the papillary type of ductal
      carcinoma in situ. Some 17% of all papilloma are associated with (synchronous)
      intraductal or invasive carcinoma, but these also act as an indicator for
      subsequent (metachronous) carcinoma. As a consequence, in minimally invasive
      biopsy papilloma has to be classified as B3 and usually has to be followed by
      surgical excision.

PMID- 16896681
TI  - [Sudden decrease in vision in craniocarpotarsal dystrophy].

PMID- 16896680
TI  - [The aging lens--new concepts for lens aging].
AB  - Epidemiological changes within the next decades will lead to an increase in the
      world population and to life expectancy. These changes will in turn lead to an
      increase in age correlated lens opacities and cataracts. Intensive research on
      cataract formation therefore becomes more and more important for socioeconomic
      reasons. In addition to the known risk factors, increased attention is currently
      being paid to oxidative processes. Typically, changes in the old lens are caused
      by the failure of protective systems and an accumulation of metabolic end
      products and their influence on light transmission. Advanced glycation end
      products and their potential inhibition seem to play a key role.

PMID- 16896682
TI  - [Hemicentral retinal artery occlusion associated with moyamoya syndrome].
AB  - Moyamoya syndrome is a rare cerebrovascular disorder characterized by bilateral
      progressive supraclinoidal stenosis or occlusion of the internal carotid artery
      and development of collateral vessels in the lenticulostriate region. The
      syndrome manifests itself in association with another disease or other clinical
      symptoms. We present the case of a 12-year-old girl with hemicentral retinal
      artery occlusion due to moyamoya syndrome associated with clinical and laboratory
      findings of presumed systemic lupus erythematosus.

PMID- 16896683
TI  - [Glaucoma and oxidative stress. Determination of malondialdehyde--a product of
      lipid peroxidation].
AB  - BACKGROUND: Primary open-angle glaucoma (POAG) is a multifactorial disease, in
      which aging, race, genetic disposition, vascular status, probably inflammation,
      and maybe oxidative stress may play a specific role. We wanted to know if by
      using a common test for a specific oxidative stress product differences would be
      found in the aqueous humor and serum of patients with POAG, cataract without
      pseudoexfoliation, cataract with pseudoexfoliation, and volunteers without ocular
      disease. PATIENTS AND METHODS: We examined the aqueous humor of 33 patients with
      POAG, 111 patients with cataract without pseudoexfoliation, 39 patients with
      cataract and pseudoexfoliation syndrome and the serum of all three groups plus of
      43 volunteers without ocular disease. Malondialdehyde as an oxidative stress
      product of peroxidation of lipids was proven by thiobarbituric acid-reacting
      substances (TBARS). RESULTS: The amount of TBARS is given in micromol/l: (1) in
      the serum of the group with cataract 1.176, with cataract and pseudoexfoliation
      1.019, with POAG 0.992, and with healthy eyes 0.983; (2) in the aqueous humor of
      the group with cataract 0.279, with cataract and pseudoexfoliation 0.274, and
      with POAG 0.298. There were no statistically significant differences of TBARS
      (p<0.05) in either the aqueous humor or in the serum of patients with POAG in
      comparison to those patients without POAG. However, there was a significantly
      positive correlation between the values in the serum and the aqueous humor.
      CONCLUSION: For the first time malondialdehyde as a product of lipid peroxidation
      was determined in the aqueous humor of glaucomatous eyes. With the TBARS method
      used in our study, it was not possible to detect statistically significant
      differences of the lipid peroxidation product malondialdehyde between patients
      with or without POAG. It has to be taken into account that the cataract of the
      patients in the control group might be a disease per se caused by at least a
      certain amount of oxidative stress and that these subjects might therefore not be
      ideal as a control group.

PMID- 16896684
TI  - [Evaluation of dynamic contour tonometry in penetrating keratoplasties].
AB  - PURPOSE: The PASCAL dynamic contour tonometer (DCT) adapted to the corneal
      geometry is a new approach for digital measurement of intraocular pressure (IOP).
      The purpose of this study was to evaluate the DCT vs Goldmann applanation
      tonometry (GAT) in penetrating keratoplasties. METHOD: We included 92 consecutive
      eyes after penetrating keratoplasty (57 without sutures, 32 with 2 running
      sutures, 3 with 1 running suture) in this prospective cross-sectional study. The
      mean outcome measurements were central corneal power (Zeiss ophthalmometer) and
      central corneal thickness (ultrasound pachymetry Tomey AL-1000). IOP was
      evaluated in consecutive measurements including 3x DCT and 1x GAT. RESULTS: The
      mean IOP measured with DCT was 18.3+/-4.0 mmHg in contrast to GAT with 14.3+/-4.1
      mmHg (p<0.001). Both methods showed a strong correlation of IOP values (r=0.74,
      p<0.001). The quality of measurement in keratoplasties after complete suture
      removal was between Q1 and Q3 in 88% with DCT in contrast to 59% with two running
      sutures. Three values with a reproducibility of 0.97 (Cronbach's alpha) could be
      obtained in 53 eyes without sutures and with a reproducibility of 0.94
      (Cronbach's alpha) in 20 eyes (62.5%) with 2 running sutures. DCT or GAT did not
      correlate with central corneal thickness. The mean astigmatism did not differ
      between keratoplasties without sutures (4.86+/-3.35 D) or with two running
      sutures (4.2+/-2.8 D, p=0.38). CONCLUSIONS: The DCT provides reproducible IOP
      measurements in penetrating keratoplasties with significantly higher values in
      comparison to GAT. Nevertheless, as known for GAT, postoperative intrastromal
      corneal sutures after penetrating keratoplasty disturb the exact DCT measurement
      as well.

PMID- 16896685
TI  - [Wavefront analysis for the diagnosis of subclinical keratoconus].
AB  - BACKGROUND: The entity of subclinical keratoconus (SKC) has not been defined
      sufficiently yet. The aim of the study was to describe ocular wavefront
      aberrations of clinically inconspicuous fellow eyes in patients with early
      keratoconus (KC) as a model of SKC and to assess the feasibility of higher-order
      wavefront analysis to discriminate eyes with SKC from normal eyes. METHODS: This
      prospective study included eight clinically inconspicuous fellow eyes of eight
      patients with newly detected KC in the contralateral eye and a paracentral
      inferior-superior difference (PISD) <1.4 D. In total, 15 eyes of 12 patients with
      newly diagnosed KC and a PISD >1.4 D were included as positive controls and 71
      healthy eyes of 40 patients served as negative controls. The wavefront error was
      measured in all eyes with a Hartmann-Shack sensor. Discriminant analysis was
      performed with input from ocular HOA data and PISD. Receiver operating
      characteristic (ROC) curves were plotted for PISD, single Zernike coefficients,
      and for the output values of the discriminant functions to investigate their
      usefulness for discrimination between SKC eyes, early KC eyes, and healthy
      controls. RESULTS: There were significant differences between inconspicuous
      fellow eyes (group 2) and controls (group 3) for PISD, for the coefficients Z3(
      3), Z3(-1), Z4(0) and Z5(-1), and for the output values of the discriminant
      functions. The latter discriminated between groups 2 and 3 with maximum
      sensitivity and specificity (A(z) ROC=1), whereas discriminative ability was
      considerably lower for single Zernike coefficients. CONCLUSION: Single Zernike
      coefficients did not appear to be useful for the detection of SKC. Using
      discriminant analysis, from PISD and higher-order Zernike coefficients a metric
      with very high discriminative ability between normal and SKC eyes could be
      constructed.

PMID- 16896686
TI  - Arthropod mechanoreceptive hairs: modeling the directionality of the joint.
AB  - Stimulus transformation in arthropod mechanoreceptive hairs is dominated by the
      mechanical properties of both the hair shaft and the hair's articulation. Here a
      mathematical model of the hair's articulation is developed based on simple
      relationships relevant for every anisotropic articulation. The mechanical
      behavior regarding deflection under load of a variety of hairs can be described
      quantitatively by using only two (in the case of double symmetric
      characteristics) or four parameters (in the case of only one symmetry): (1) joint
      stiffness S p in the preferred direction of deflection, (2) joint stiffness St in
      a plane transversal to the preferred direction, and (3, 4) the values of
      stiffness S for opposite directions of deflection. The applicability of the model
      was tested by measuring these stiffnesses S of spider tactile hair joints by
      deflecting the hairs statically in different directions. For comparison, data in
      the literature on insect and spider hairs sensitive to air flow were analyzed.
      The equation presented describes the directional characteristics of a wide range
      of structurally different cuticular hairs. It can also be used as a mathematical
      description of the joint mechanics when modeling the mechanics of hairs, for
      instance, by applying methods such as Finite Element Analysis.

PMID- 16896687
TI  - Defective transfer of seminal-fluid materials during matings of semi-fertile
      fruitless mutants in Drosophila.
AB  - In context of the semi-sterility exhibited by Drosophila males expressing certain
      mating-enabling fruitless (fru) mutant genotypes, we examined the transfer of
      seminal fluid using a transgene that encodes the Sex Peptide (SP) oligopeptide
      fused to Green Fluorescent Protein (GFP). We found that this fusion construct
      expresses SP-GFP in a valid manner within accessory glands of the male
      reproductive system in normal and fru-mutant males. Transfer of SP-GFP to live
      females was readily detectable during and after copulation. With respect to the
      pertinent combinations of fru mutations, we demonstrated that these abnormal
      genotypes cause males to transmit mating-related materials in two aberrant ways:
      one involving whether any seminal-fluid entities are transferred at all during a
      given mating; the other revealing an intriguing aspect of these fruitless
      effects, such that the mutations in question cause males to transfer female
      affecting materials in a manner that varies among copulations. In this regard,
      certain mutant males that do not transfer SP nevertheless are able to transfer
      sperm: a fru-mated female possessing no GFP who was not fecund initially could
      produce progeny when seminal-fluid proteins were subsequently supplied by mating
      with a male that was spermless owing to the effects of a tudor mutation.

PMID- 16896688
TI  - A method for two-dimensional characterization of animal vibrational signals
      transmitted along plant stems.
AB  - Conventional approaches to measuring animal vibrational signals on plant stems
      use a single transducer to measure the amplitude of vibrations. Such an approach,
      however, will often underestimate the amplitude of bending waves traveling along
      the stem. This occurs because vibration transducers are maximally sensitive along
      a single axis, which may not correspond to the major axis of stem motion.
      Furthermore, stem motion may be more complex than that of a bending wave
      propagating along a single axis, and such motion cannot be described using a
      single transducer. Here, we describe a method for characterizing stem motion in
      two dimensions by processing the signals from two orthogonally positioned
      transducers. Viewed relative to a cross-sectional plane, a point on the stem
      surface moves in an ellipse at any one frequency, with the ellipse's major axis
      corresponding to the maximum amplitude of vibration. The method outlined here
      measures the ellipse's major and minor axes, and its angle of rotation relative
      to one of the transducers. We illustrate this method with measurements of stem
      motion during insect vibrational communication. It is likely the two-dimensional
      nature of stem motion is relevant to insect vibration perception, making this
      method a promising avenue for studies of plant-borne transmission.

PMID- 16896689
TI  - Effect of extract of Phyllanthus niruri on crystal deposition in experimental
      urolithiasis.
AB  - Phyllanthus niruri (Pn) is a plant that has been shown to interfere in the growth
      and aggregation of calcium oxalate (CaOx) crystals. In the present study we
      evaluated the effect of Pn on the preformed calculus induced by introduction of a
      CaOx seed into the bladder of male Wistar rats. Pn treatment (5 mg/ rat/day) was
      initiated immediately or 30 days after CaOx seeding and thus in the presence of a
      preformed calculus. Animals were sacrificed 50 or 70 days after surgery. The
      resulting calculi were weighed and analyzed by X-ray diffraction,
      stereomicroscopy and scanning electronic microscopy. Precocious Pn treatment
      reduced the number (75%, P < 0.05) and the weight (65%, P < 0.05) of calculi that
      frequently exhibited a matrix-like material on its surface, compared to the
      untreated CaOx group. In contrast, Pn treatment in the presence of a preformed
      calculus did not prevent further calculus growth; rather, it caused an impressive
      modification in its appearance and texture. Calculi from Pn-treated animals had a
      smoother, homogeneous surface compared to the spicule shape of calculi found in
      the untreated CaOx group. XRD analysis revealed the precipitation of struvite
      crystals over the CaOx seed and Pn did not change the crystalline composition of
      the calculi. This suggests that Pn interfered with the arrangement of the
      precipitating crystals, probably by modifying the crystal-crystal and/or crystal
      matrix interactions. Results suggest that Pn may have a therapeutic potential,
      since it was able to modify the shape and texture of calculi to a smoother and
      probably more fragile form, which could contribute to elimination and/or
      dissolution of calculi.

PMID- 16896690
TI  - Preservation of urine samples for metabolic evaluation of stone-forming patients.
AB  - Metabolic evaluation of stone-forming (SF) patients is based on the determination
      of calcium, oxalate, citrate, uric acid and other parameters in 24-h urine
      samples under a random diet. A reliable measurement of urinary oxalate requires
      the collection of urine in a receptacle containing acid preservative. However,
      urinary uric acid cannot be determined in the same sample under this condition.
      Therefore, we tested the hypothesis that the addition of preservatives (acid or
      alkali) after urine collection would not modify the results of those lithogenic
      parameters. Thirty-four healthy subjects (HS) were submitted to two non
      consecutive collections of 24-h urine. The first sample was collected in a
      receptacle containing hydrochloric acid (HCl 6 N) and the second in a dry plastic
      container, with HCl being added as soon as the urine sample was received at the
      laboratory. Additionally, 34 HS and 34 SF patients collected a spot urine sample
      that was divided into four aliquots, one containing HCl, another containing
      sodium bicarbonate (NaHCO(3 )5 g/l), and two others in which these two
      preservative agents were added 24 h later. Urinary oxalate, calcium, magnesium,
      citrate, creatinine and uric acid were determined. Urinary parameters were also
      evaluated in the presence of calcium oxalate or uric acid crystals. Mean values
      of all urinary parameters obtained from previously acidified 24-h urine samples
      did not differ from those where acid was added after urine collection. The same
      was true for spot urine samples, with the exception of urinary citrate that
      presented a slight albeit significant change of 5.9% between samples in HS and
      3.1% in SF. Uric acid was also not different between pre- and post-alkalinized
      spot urine samples. The presence of crystals did not alter these results. We
      concluded that post-delivery acidification or alkalinization of urine samples
      does not modify the measured levels of urinary oxalate, calcium, magnesium,
      creatinine and uric acid, and that the change on citrate was not relevant, hence
      allowing all parameters to be determined in a single urine sample, thus avoiding
      the inconvenience and cost of multiple 24-h urine sample collections.

PMID- 16896692
TI  - Visualization of intrarenal vessels by 3.0-T MR angiography in comparison with
      digital subtraction angiography using renal specimens.
AB  - BACKGROUND: MRI at 3.0 T enables high-spatial resolution for renal MR
      angiography. OBJECTIVE: Evaluation of an arterial tree model in animal kidney
      specimens with comparison of digital subtraction angiography (DSA) and high-field
      MRI to find out the maximum spatial resolution of intrarenal vessels. It was
      considered that objective quantitation of angiogram quality could be achieved.
      MATERIALS AND METHODS: A total of 27 pig kidney specimens were examined by MR
      angiography (flash 3D) using a 3.0-T scanner (TRIO; Siemens, Erlangen, Germany)
      with an eight-channel head coil and a voxel size of 0.9x0.9x1.1 mm in the early
      arterial phase after implantation of a 4F catheter in the renal artery. DSA
      (Integris, Philips, Best, The Netherlands) was performed immediately after the
      MRI. With the help of semiautomated segmentation, all vessels were marked for
      comparison of the vessel trees. The Wilcoxon rank test was used for statistical
      evaluation of vessel numbers and branching depths. RESULTS: Objective comparison
      between DSA and MR angiography was achieved. High-field MR angiography had the
      ability to depict vessels up to the seventh branching on average. Significant
      differences in vessel delineation and counts were found from the fifth level of
      intrarenal branching onwards with DSA showing an advantage. CONCLUSION: High
      field MRI has great potential in the detection of intrarenal arteries and is
      comparable to DSA in visualization of the central intrarenal vessel tree.

PMID- 16896691
TI  - Deregulation of the p16-cyclin D1/cyclin-dependent kinase 4-retinoblastoma
      pathway involved in the rat bladder carcinogenesis induced by terephthalic acid
      calculi.
AB  - Prolonged cell proliferation in response to irritation by calculi may itself
      evoke malignant transformation of the urothelium. However, the molecular
      mechanisms underlying this process are still unknown. The aim of the present
      study was to investigate cell cycle regulatory mechanisms in bladder
      carcinogenesis induced by bladder calculi. Six-week-old Wistar rats were
      consecutively fed a diet containing 5% terephthalic acid (TPA), 5% TPA plus 4%
      sodium bicarbonate (NaHCO(3)), 4% NaHCO(3), or basal diet for 48 weeks. Animals
      were killed at weeks 12, 24, and 48. Treatment with 5% TPA caused high incidences
      of bladder calculi, preneoplastic lesions, and neoplastic lesions.
      Immunohistochemical examination revealed overexpression of cyclin D1, cyclin
      dependent kinase 4 (Cdk4), retinoblastoma (Rb), and proliferating cell nuclear
      antigen (PCNA) in bladder preneoplastic and neoplastic lesions. In contrast, p16
      expression was reduced or absent. These results were confirmed by immunoblotting
      analysis. Quantitation of mRNA by real-time reverse transcription-polymerase
      chain reaction (RT-PCR) showed a significant increase in cyclin D1 and PCNA mRNA
      in tumor cells. None of the 16 transitional cell carcinomas (TCCs) had ras
      mutations as examined by PCR-single strand conformational polymorphism (PCR-SSCP)
      analysis. These results suggested that deregulation of p16-cyclin D1/Cdk4-Rb
      pathway, but not oncogenic activation of ras, plays a crucial role in bladder
      tumorigenesis induced by bladder calculi.

PMID- 16896693
TI  - Pericardial sac perforation: a rare complication of neonatal nasogastric tube
      feeding.
AB  - The insertion of a nasogastric tube for feeding and gastric aspiration is a
      common practice in the care of newborns, especially if they are preterm and
      unwell. Esophageal perforation is a rare but serious complication of this
      procedure. Associated perforation of the pericardial sac is an unusual, severe,
      and previously unreported complication of nasogastric tube feeding in a neonate.
      We present an illustrative case.

PMID- 16896695
TI  - Whole-body MRI of Langerhans cell histiocytosis: comparison with radiography and
      bone scintigraphy.
AB  - BACKGROUND: In Langerhans cell histiocytosis (LCH) evaluation of the extent of
      disease is one of the major predictors of patient outcome. Historically this is
      undertaken using plain radiography and bone scintigraphy. Recently, whole-body
      (WB) MRI has been reported to be useful in detecting skeletal and extraskeletal
      metastases in both adults and children. OBJECTIVE: To evaluate the usefulness of
      WB MRI in patients with LCH in comparison with plain radiography and bone
      scintigraphy. MATERIALS AND METHODS: In nine children (1-7 years of age; mean 3.3
      years) who had a pathological diagnosis of LCH and had either plain radiography
      or bone scintigraphy for comparison, 43 WB MR examinations were performed.
      Skeletal and extraskeletal lesions of the disease on WB MRI were compared with
      those on plain radiography and bone scintigraphy. RESULTS: LCH showed unifocal
      single-system involvement in one patient, multifocal single-system involvement in
      three, and multifocal multisystem disease in five. WB MRI identified additional
      skeletal lesions in three (38%) of eight patients, compared with plain
      radiography, and in two (25%) of eight, compared with bone scintigraphy. WB MRI
      detected extraskeletal lesions of the disease in five (56%) of the nine patients
      exclusively, except for one patient whose lung lesions were also detected on
      plain radiography. In two patients, treatment was changed according to WB MRI
      findings. CONCLUSION: WB MRI is a useful initial and follow-up diagnostic method
      to assess the extent of LCH because WB MRI not only identifies more skeletal
      lesions of the disease than do plain radiography and bone scintigraphy, but also
      detects extraskeletal lesions of the disease.

PMID- 16896694
TI  - Radiographic appearance of pediatric cardiovascular transcatheter devices.
AB  - The treatment of congenital heart disease has been revolutionized by the
      availability of transcatheter devices. These advances in interventional pediatric
      cardiology require that both treating physicians and radiologists develop a more
      thorough understanding of the appearance of these devices on chest radiographs.
      Furthermore, recognition of appropriate versus inappropriate placement of
      transcatheter devices is essential to the care of patients with congenital heart
      disease. Knowledge of the radiographic appearance of devices used by
      interventional pediatric cardiologists can allow a radiologist to make better
      clinical assessments and detect possible complications given a limited clinical
      history.

PMID- 16896698
TI  - Panel discussion.

PMID- 16896699
TI  - Vendor question and answer panel.

PMID- 16896700
TI  - Assessment of pulmonary venous stenosis after radiofrequency catheter ablation
      for atrial fibrillation by magnetic resonance angiography: A comparison of linear
      and cross-sectional area measurements.
AB  - One of the recognised complications of catheter ablation is pulmonary venous
      stenosis. The aim of this study was to compare two methods of evaluation of
      pulmonary venous diameter for follow-up assessment of the above complication: (1)
      a linear approach evaluating two main diameters of the vein, (2)
      semiautomatically measured cross-sectional area (CSA). The study population
      consists of 29 patients. All subjects underwent contrast-enhanced magnetic
      resonance angiography (CeMRA) of the pulmonary veins (PVs) before and after the
      ablation; 14 patients were also scanned 3 months later. PV diameter was evaluated
      from two-dimensional multiplanar reconstructions by measuring either the linear
      diameter or CSA. A comparison between pulmonary venous CSA and linear
      measurements revealed a systematic difference in absolute values. This difference
      was not significant when comparing the relative change CSA and quadratic
      approximation using linear extents (linear approach). However, a trend towards
      over-estimation of calibre reduction was documented for the linear approach.
      Using CSA assessment, significant PV stenosis was found in ten PVs (8%) shortly
      after ablation. Less significant PV stenosis, ranging from 20 to 50% was
      documented in other 18 PVs (15%). CeMRA with CSA assessment of the PVs is
      suitable method for evaluation of PV diameters.

PMID- 16896701
TI  - Gadolinium contrast media are more nephrotoxic than iodine media. The importance
      of osmolality in direct renal artery injections.
AB  - A study was undertaken of the role of osmotoxicity in gadolinium (Gd) and iodine
      contrast media (CM) nephrotoxicity in ischemic porcine kidneys. Test solutions:
      mannitol iso-osmotic to 0.5 M: gadopentetate (1.96 Osm/kg H2O), 0.5 M:
      gadodiamide (0.78 Osm/kg H2O) and 0.5 M: iohexol (190 mg I/ml, 0.42 Osm/kg H2O).
      Each solution was injected [3 ml/kg body weight (BW)] into the balloon-occluded
      (10 min) renal artery of eight left-sided nephrectomized pigs. The plasma half
      life of a glomerular filtration rate (GFR) marker was used to compare their
      effects on GFR 1-3 h post-injection. The median half-lives of the GFR marker
      after injection of gadopentetate (1,730 min) and mannitol 1.96 Osm/kg H2O (2,782
      min) did not differ statistically (P = 0.28), but were significantly longer than
      after all other solutions (P < 0.001). There was no significant difference (P =
      0.06) between gadodiamide (218 min) and mannitol 0.82 Osm/kg H2O (169 min), while
      there was (P = 0.03) between iohexol (181 min) and mannitol 0.43 Osm/kg H2O (148
      min). The difference between gadodiamide and iohexol was significant (P = 0.01).
      Reduction in GFR, as a marker of nephrotoxicity, induced by gadopentetate
      correlated with its high osmolality, while the effect of gadodiamide and iohexol
      may include chemotoxicity. Iohexol molecules were less nephrotoxic than the Gd-CM
      molecules and contain three-times the number of attenuating atoms per molecule.

PMID- 16896702
TI  - Evaluation of quantitative parametric analysis for characterization of breast
      lesions in contrast-enhanced MR mammography.
AB  - Our aim was to evaluate quantitative parametric analysis for characterization of
      breast lesions in contrast-enhanced magnetic resonance (MR) mammography. In 62
      patients, contrast-enhanced MR mammography revealed 75 suspicious lesions, of
      which 18 were benign and 57 were malignant. The quantitative parametric analysis
      delineates signal intensity changes of contrast-enhanced lesions on a pixel-by
      pixel basis. The initial rate of enhancement is coded by color intensity: a slow
      rate is coded to dark; a fast rate, bright. The postinitial enhancement change is
      coded by color hue: blue for increasing signal intensity, green for plateau, and
      red for decrease in signal intensity. Malignant lesions showed a significantly
      higher number of bright-red (P = 0.004) and medium-red (P < 0.001) pixels than
      benign lesions. Benign lesions showed significantly more blue pixels than did
      malignant lesions (P = 0.010). Of the 75 lesions, 72 (96%) showed heterogeneous
      distribution of pixel color hue. Quantitative parametric analysis of contrast
      kinetics in lesions can replace the subjective manual region of interest (ROI)
      method and makes a step toward standardization of MR mammography. It allows
      quantitative evaluation of different contrast kinetics parameters in contrast
      enhanced breast lesions.

PMID- 16896703
TI  - Should 3K zoom function be used for detection of pneumothorax in cesium
      iodide/amorphous silicon flat-panel detector radiographs presented on 1K-matrix
      soft copies?
AB  - The purpose of the study was to evaluate observer performance in the detection of
      pneumothorax with cesium iodide and amorphous silicon flat-panel detector
      radiography (CsI/a-Si FDR) presented as 1K and 3K soft-copy images. Forty
      patients with and 40 patients without pneumothorax diagnosed on previous and
      subsequent digital storage phosphor radiography (SPR, gold standard) had follow
      up chest radiographs with CsI/a-Si FDR. Four observers confirmed or excluded the
      diagnosis of pneumothorax according to a five-point scale first on the 1K soft
      copy image and then with help of 3K zoom function (1K monitor). Receiver
      operating characteristic (ROC) analysis was performed for each modality (1K and
      3K). The area under the curve (AUC) values for each observer were 0.7815, 0.7779,
      0.7946 and 0.7066 with 1K-matrix soft copies and 0.8123, 0.7997, 0.8078 and
      0.7522 with 3K zoom. Overall detection of pneumothorax was better with 3K zoom.
      Differences between the two display methods were not statistically significant in
      3 of 4 observers (p-values between 0.13 and 0.44; observer 4: p = 0.02). The
      detection of pneumothorax with 3K zoom is better than with 1K soft copy but not
      at a statistically significant level. Differences between both display methods
      may be subtle. Still, our results indicate that 3K zoom should be employed in
      clinical practice.

PMID- 16896706
TI  - The barley serine/threonine kinase gene Rpg1 providing resistance to stem rust
      belongs to a gene family with five other members encoding kinase domains.
AB  - The barley (Hordeum vulgare L.) stem rust (Puccinia graminis f. sp. tritici)
      resistance gene Rpg1 encodes a serine/threonine protein kinase with two tandem
      kinase domains. The Rpg1 gene family was identified from the cv. Morex and
      consists of five additional members with divergent homology to Rpg1. All family
      members encode serine/threonine kinase-like proteins with at least one predicted
      catalytically active kinase domain. The five family members were sequenced from
      cDNA and genomic DNA and genetically mapped. The family member most closely
      related to Rpg1, ABC1037, is located on chromosome 1(7H) bin 01, very near
      (approximately 50 kb) but not co-segregating with Rpg1. Two others, ABC1036 and
      ABC1040, are closely related to each other and tightly linked on chromosome 7(5H)
      bin 07. ABC1041 mapped to chromosome 7(5H) bin 13, tightly linked to the rust
      resistance genes rpg4 and Rpg5 providing resistance to barley stem rust pathotype
      QCC and rye stem rust pathotype 92-MN-90, respectively, but segregated away in a
      high-resolution population. ABC1063 was localized to chromosome 4(4H) bin 6. An
      interesting Rpg1 allele that appears to be the result of unequal recombination
      between Rpg1 and ABC1037 was characterized. No known resistance loci cosegregated
      with any family members, however characterization of the Rpg1 family has provided
      insight into the evolution of this novel gene family and may present tools for
      understanding the functional domains of Rpg1. The genetic mapping, gene
      structures, and analysis of amino-acid sequences of the Rpg1 gene family members
      are presented.

PMID- 16896704
TI  - Large-sized hepatocellular carcinoma (HCC): a neoadjuvant treatment protocol with
      repetitive transarterial chemoembolization (TACE) before percutaneous MR-guided
      laser-induced thermotherapy (LITT).
AB  - This study aims to evaluate the efficacy and safety of a neoadjuvant treatment
      protocol with repeated transarterial chemoembolization (TACE) before MR-guided
      laser-induced thermotherapy (LITT) for large-sized hepatocellular carcinomas
      (HCC). Repeated TACE (mean, 3.5 treatments per patient) was performed in 48
      patients with neoadjuvant intention (the largest lesion was between 50 and 80 mm
      in diameter, and there were no more than five lesions). For the TACE treatment,
      we used 10 mg/m(2) mitomycin, 10 ml/m(2) Lipiodol and microspheres. The tumor
      volume was measured by MRI. Lipiodol retention of the tumors was evaluated with
      CT. After the diameter of the tumors had decreased to less than 50 mm, the
      patients were treated with MR-guided LITT 4 to 6 weeks after embolization.
      Repeated TACE reduced the tumor size in 32 patients (66.7%), forming the basis
      for performing MR-guided LITT procedures. These patients received one to four
      laser treatments (mean, 1.9 per patient) for tumor ablation, resulting in a
      median survival of 36.0 months after the first treatment. For the remaining
      patients, no reduction in tumor size was achieved in 12 patients and disease
      progression in 4 patients. Neoadjuvant TACE appears to be an effective treatment
      of large-sized HCC, which extends the indication for MR-guided LITT.

PMID- 16896707
TI  - A new test for family-based association mapping with inbred lines from plant
      breeding programs.
AB  - Association mapping holds great promise for the detection of quantitative trait
      loci (QTL) in plant breeding populations. The main objectives of this study were
      to (1) adapt the quantitative pedigree disequilibrium test to typical pedigrees
      of inbred lines produced in plant breeding programs, (2) compare the newly
      developed quantitative inbred pedigree disequilibrium test (QIPDT) with the
      commonly employed logistic regression ratio test (LRRT), with respect to the
      power and type I error rate of QTL detection, and (3) demonstrate the use of the
      QIPDT by applying it to flowering data of European elite maize inbreds. QIPDT and
      LRRT were compared based on computer simulations modeling 55 years of hybrid
      maize breeding in Central Europe. Furthermore, we applied QIPDT to a cross
      section of 49 European elite maize inbred lines genotyped with 722 amplified
      fragment length polymorphism markers and phenotyped in four environments for days
      to anthesis. Compared to LRRT, the power to detect QTL was higher with QIPDT when
      using data collected routinely in plant breeding programs. Application of QIPDT
      to the 49 European maize inbreds resulted in a significant (P < 0.05) association
      located at a position for which a consensus QTL was detected in a previous study.
      The results of our study suggested that QIPDT is a promising QTL detection method
      for data collected routinely in plant breeding programs.

PMID- 16896708
TI  - Genetic drift and selection effects of modified recurrent full-sib selection
      programs in two F2 populations of European flint maize.
AB  - Selection response of a modified recurrent full-sib (FS) selection scheme
      conducted in two European flint F(2) maize (Zea mays L.) populations was re
      evaluated. Our objectives were to (1) determine the selection response for per se
      and testcross performance in both populations and (2) separate genetic effects
      due to selection from those due to random genetic drift. Modified recurrent FS
      selection was conducted at three locations using an effective population size
      N(e) = 32 and a selection rate of 25% for a selection index, based on grain yield
      and grain moisture. Recombination was performed according to a pseudo-factorial
      mating scheme. Selection response was assessed using a population diallel
      including the source population and advanced selection cycles, as well as
      testcrosses with unrelated inbred line testers and the parental F(1) generation.
      Selection response per cycle was significant for grain yield and grain moisture
      in both populations. Effects of random genetic drift caused only a small
      reduction in the selection response. No significant selection response was
      observed for testcrosses, suggesting that for heterotic traits, such as grain
      yield, a high frequency of favorable alleles in the elite tester masked the
      effects of genes segregating in the populations. We conclude that our modified
      recurrent FS selection is an alternative to other commonly applied
      intrapopulation recurrent selection schemes, and some of its features may also be
      useful for increasing the efficiency of interpopulation recurrent selection
      programs.

PMID- 16896709
TI  - Identification of genetic loci associated with ear-emergence in bread wheat.
AB  - A doubled haploid population constructed from a cross between the South
      Australian wheat cultivars 'Trident' and 'Molineux' was grown under winter field
      conditions, under field conditions over summer and under artificial light both
      with and without vernalisation. The duration from planting to ear-emergence was
      recorded and QTL associated with heading date were detected using a previously
      constructed genetic linkage map. Associations were shown with chromosomal regions
      syntenous to previously identified photoperiod (Ppd-B1) and vernalisation (Vrn
      A1) sensitive loci. Additional QTL associated with time to heading were also
      identified on chromosomes 1A, 2A, 2B, 6D, 7A and 7B. Comparisons between the
      genetic associations observed under the different growing conditions allowed the
      majority of these loci to be classified as having either photoperiod-sensitive,
      vernalisation-sensitive or earliness per se actions. The identification of a
      photoperiod-sensitive QTL on chromosome 1A provides evidence for a wheat gene
      possibly homoeologous to Ppd-H2 previously identified on chromosome 1H of barley.
      The occurrence of a putative major gene for photoperiod sensitivity observed on
      chromosome 7A is presented. The combined additive effects at these loci accounted
      for more than half the phenotypic variance in the duration from planting to ear
      emergence in this population. The possible role of these loci on the adaptation
      of wheat in Australia is discussed.

PMID- 16896710
TI  - Powdery mildew resistance in roses: QTL mapping in different environments using
      selective genotyping.
AB  - Podosphaera pannosa, the causal agent of rose powdery mildew, hampers the
      production of cut roses throughout the world. A major tool to control this
      disease is the use of resistant plant material. Single resistance genes, like
      Rpp1, may be overcome within a few years by high risk pathogens like powdery
      mildews. Durable resistance could be achieved using quantitative resistances.
      Here we describe mapping of QTLs for resistance to P. pannosa in six different
      environments (artificial and natural infections in the greenhouse over 3 years
      and natural infections in the field over 2 years). AFLPs, RGAs and other marker
      types were used to construct an integrated linkage map for the diploid population
      97/7 containing 233 markers. In a selective genotyping procedure, marker
      segregation was analysed for 170 of the up to 270 phenotyped individuals. We
      identified seven linkage groups with an average length of 60 cM, corresponding to
      seven rose chromosomes in the haploid set. Using an LOD significance threshold of
      3.9 we detected a total of 28 QTLs for the nine powdery mildew disease scores
      under analysis. Using the data from artificial inoculations with powdery mildew
      race 9, three resistance QTLs explaining about 84% of the variability were
      mapped. Twelve and 15 QTLs were detected for resistance to naturally occurring
      infections in the greenhouse and in the field, respectively, over several years.

PMID- 16896711
TI  - Development of simple sequence repeat markers specific for the Lr34 resistance
      region of wheat using sequence information from rice and Aegilops tauschii.
AB  - Hexaploid wheat (Triticum aestivum L.) originated about 8,000 years ago from the
      hybridization of tetraploid wheat with diploid Aegilops tauschii Coss. containing
      the D-genome. Thus, the bread wheat D-genome is evolutionary young and shows a
      low degree of polymorphism in the bread wheat gene pool. To increase marker
      density around the durable leaf rust resistance gene Lr34 located on chromosome
      7DS, we used molecular information from the orthologous region in rice. Wheat
      expressed sequence tags (wESTs) were identified by homology with the rice genes
      in the interval of interest, but were monomorphic in the 'Arina' x 'Forno'
      mapping population. To derive new polymorphic markers, bacterial artificial
      chromosome (BAC) clones representing a total physical size of approximately 1 Mb
      and belonging to four contigs were isolated from Ae. tauschii by hybridization
      screening with wheat ESTs. Several BAC clones were low-pass sequenced, resulting
      in a total of approximately 560 kb of sequence. Ten microsatellite sequences were
      found, and three of them were polymorphic in our population and were genetically
      mapped close to Lr34. Comparative analysis of marker order revealed a large
      inversion between the rice genome and the wheat D-genome. The SWM10
      microsatellite is closely linked to Lr34 and has the same allele in the three
      independent sources of Lr34: 'Frontana', 'Chinese Spring', and 'Forno', as well
      in most of the genotypes containing Lr34. Therefore, SWM10 is a highly useful
      marker to assist selection for Lr34 in breeding programs worldwide.

PMID- 16896712
TI  - Prediction of single-cross hybrid performance for grain yield and grain dry
      matter content in maize using AFLP markers associated with QTL.
AB  - Prediction methods to identify single-cross hybrids with superior yield
      performance have the potential to greatly improve the efficiency of commercial
      maize (Zea mays L.) hybrid breeding programs. Our objectives were to (1) identify
      marker loci associated with quantitative trait loci for hybrid performance or
      specific combining ability (SCA) in maize, (2) compare hybrid performance
      prediction by genotypic value estimates with that based on general combining
      ability (GCA) estimates, and (3) investigate a newly proposed combination of the
      GCA model with SCA predictions from genotypic value estimates. A total of 270
      hybrids was evaluated for grain yield and grain dry matter content in four Dent x
      Flint factorial mating experiments, their parental inbred lines were genotyped
      with 20 AFLP primer-enzyme combinations. Markers associated significantly with
      hybrid performance and SCA were identified, genotypic values and SCA effects were
      estimated, and four hybrid performance prediction approaches were evaluated. For
      grain yield, between 38 and 98 significant markers were identified for hybrid
      performance and between zero and five for SCA. Estimates of prediction efficiency
      (R (2)) ranged from 0.46 to 0.86 for grain yield and from 0.59 to 0.96 for grain
      dry matter content. Models enhancing the GCA approach with SCA estimates resulted
      in the highest prediction efficiency if the SCA to GCA ratio was high. We
      conclude that it is advantageous for prediction of single-cross hybrids to
      enhance a GCA-based model with SCA effects estimated from molecular marker data,
      if SCA variances are of similar or larger importance as GCA variances.

PMID- 16896713
TI  - Identification and validation of molecular markers linked to the leaf rust
      resistance gene Lr19 in wheat.
AB  - A leaf rust resistance gene Lr19 on the chromosome 7DL of wheat derived from
      Agropyron elongatum was tagged with random amplified polymorphic DNA (RAPD) and
      microsatellite markers. The F(2) population of 340 plants derived from a cross
      between the leaf rust resistant near-isogenic line (NIL) of Thatcher (Tc + Lr19)
      and leaf rust susceptible line Agra Local that segregated for dominant monogenic
      leaf rust resistance was utilized for generating the mapping population. The
      molecular markers were mapped in the F(2) derived F(3) homozygous population of
      140 seedlings. Sixteen RAPD markers were identified as linked to the alien gene
      Lr19 among which eight were in a coupling phase linkage. Twelve RAPD markers co
      segregated with Lr19 locus. Nine microsatellite markers located on the long arm
      of chromosome 7D were also mapped as linked to the gene Lr19, including 7 markers
      which co-segregated with Lr19 locus, thus generating a saturated region carrying
      25 molecular markers linked to the gene Lr19 within 10.2 +/- 0.062 cM on either
      side of the locus. Two RAPD markers S265(512) and S253(737) which flanked the
      locus Lr19 were converted to sequence characterized amplified region markers
      SCS265(512) and SCS253(736), respectively. The marker SCS265(512) was linked with
      Lr19 in a coupling phase and the marker SCS253(736) was linked in a repulsion
      phase, which when used together mimicked one co-dominant marker capable of
      distinguishing the heterozygous resistant seedlings from the homozygous
      resistant. The molecular markers were validated on NILs mostly in Thatcher
      background isogenic for 44 different Lr genes belonging to both native and alien
      origin. The validation for polymorphism in common leaf rust susceptible cultivars
      also confirmed the utility of these tightly linked markers to the gene Lr19 in
      marker-assisted selection.

PMID- 16896714
TI  - Resistance gene analogues of wheat: molecular genetic analysis of ESTs.
AB  - Using two divergent nucleotide binding site (NBS) regions from wheat sequences of
      the NBS-LRR (leucine rich repeat) class, we retrieved 211 wheat and barley NBS
      containing resistance gene analogue (RGA) expressed sequence tags (ESTs). These
      ESTs were grouped into 129 gene sequence groups that contained ESTs that were at
      least 70% identical at the DNA level over at least 200 bp. Probes were obtained
      for 89 of these RGA families and chromosome locations were determined for 72 of
      these probes using nullitetrasomic Chinese Spring wheat lines. RFLP analysis of
      49 of these RGA probes revealed 65 mappable polymorphic bands in the doubled
      haploid Cranbrook x Halberd wheat population (C x H). These bands mapped to 49
      loci in C x H. RGA loci were detected on all 21 chromosomes using the
      nullitetrasomic lines and on 18 chromosomes (linkage groups) in the C x H map.
      This identified a set of potential markers that could be developed further for
      use in mapping and ultimately cloning NBS-LRR-type disease resistance genes in
      wheat.

PMID- 16896715
TI  - Assessing the importance of genotype x environment interaction for root traits in
      rice using a mapping population II: conventional QTL analysis.
AB  - Modifying plant root systems is considered a means of crop improvement targeted
      to low-resource environments, particularly low nutrient and drought-prone
      agriculture. The identification of quantitative trait loci (QTLs) for root traits
      has stimulated marker-assisted breeding to this end, but different QTLs have been
      detected in different populations of the same species, and importantly, in the
      same population when grown in different experimental environments. The presence
      of QTL x environment interaction is implicated, and this must be characterised if
      the utility of the target QTLs is to be realised. Previous attempts to do this
      suffer from a lack of control over replicate environments and inadequate
      statistical rigour. The Bala x Azucena mapping population was grown in two
      replicate experiments of four treatment environments, a control, a low light, a
      low soil nitrogen and a low soil water treatment. After a 4 weeks growth, maximum
      root length, maximum root thickness, root mass below 50 cm, total plant dry mass,
      % root mass and shoot length were measured. A summary of the overall results is
      presented in an accompanying paper. Here, QTL analysis by composite interval
      mapping is presented. A total of 145 QTLs were detected, mapping to 37 discrete
      loci on all chromosomes. Superficial evidence of QTL x E (great difference in LOD
      score) was tested by single-marker analysis which confirmed QTL x E for five loci
      representing only five individual trait-loci interactions. Some loci appeared to
      be stable across environments. Some QTLs were clearly more or less active under
      low light, low nitrogen or drought. A few notable loci on chromosomes 1, 2, 3, 5,
      7 and 9 are briefly discussed. Also discussed are some remaining statistical
      shortcomings that will be addressed in another companion paper.

PMID- 16896716
TI  - Major gene detection for fusiform rust resistance using Bayesian complex
      segregation analysis in loblolly pine.
AB  - The presence of major genes affecting rust resistance of loblolly pine was
      investigated in a progeny population that was generated with a half-diallel
      mating of six parents. A Bayesian complex segregation analysis was used to make
      inference about a mixed inheritance model (MIM) that included polygenic effects
      and a single major gene effect. Marginalizations were achieved by using Gibbs
      sampler. A parent block sampling by which genotypes of a parent and its offspring
      were sampled jointly was implemented to improve mixing. The MIM was compared with
      a pure polygenic model (PM) using Bayes factor. Results showed that the MIM was a
      better model to explain the inheritance of rust resistance than the pure PM in
      the diallel population. A large major gene variance component estimate (> 50% of
      total variance), indicated the existence of major genes for rust resistance in
      the studied loblolly pine population. Based on estimations of parental genotypes,
      it appears that there may be two or more major genes affecting disease phenotypes
      in this diallel population.

PMID- 16896718
TI  - Joint modeling of additive and non-additive genetic line effects in single field
      trials.
AB  - A statistical approach is presented for selection of best performing lines for
      commercial release and best parents for future breeding programs from standard
      agronomic trials. The method involves the partitioning of the genetic effect of a
      line into additive and non-additive effects using pedigree based inter-line
      relationships, in a similar manner to that used in animal breeding. A difference
      is the ability to estimate non-additive effects. Line performance can be assessed
      by an overall genetic line effect with greater accuracy than when ignoring
      pedigree information and the additive effects are predicted breeding values. A
      generalized definition of heritability is developed to account for the complex
      models presented.

PMID- 16896717
TI  - Quantitative trait loci for callus initiation and totipotency in maize (Zea mays
      L.).
AB  - Induction of embryogenic callus in culture is an important step in plant
      transformation procedures, but response is genotype specific and the genetics of
      the trait are not well understood. Quantitative trait loci (QTL) were mapped in a
      set of 126 recombinant inbred lines (RILs) of inbred H99 (high Type I callus
      response) by inbred Mo17 (low Type I callus response) that were evaluated over
      two years for Type I callus response. QTL were observed in a total of eleven bins
      on eight chromosomes, including eight QTL with main effects and three epistatic
      interactions. Many of the QTL were mapped to the same or bordering chromosomal
      bins as candidate genes for abscisic acid metabolism, indicating a possible role
      for the hormone in the induction of embryogenic callus, as has previously been
      indicated in microspore embryo induction. Further examinations of allelic
      variability for known candidate genes located near the observed QTL could be
      useful for expanding the understanding of the genetic basis of induction
      embryogenic callus. The QTL observed herein could also be used in a marker
      assisted selection (MAS) program to improve the response of agronomically useful
      inbreds, but only if the resources required for MAS are lower than those required
      for phenotypic selection.

PMID- 16896719
TI  - Three non-allelic epistatically interacting methyltransferase mutations produce
      novel tocopherol (vitamin E) profiles in sunflower.
AB  - Wildtype sunflower (Helianthus annuus L.) seeds are a rich source of alpha
      tocopherol (vitamin E). The g = Tph(2) mutation disrupts the synthesis of alpha
      tocopherol, enhances the synthesis of gamma-tocopherol, and was predicted to
      knock out a gamma-tocopherol methyltransferase (gamma-TMT) necessary for the
      synthesis of alpha-tocopherol in sunflower seeds--wildtype (g(+) g(+)) lines
      accumulated > 90% alpha-tocopherol, whereas mutant (g g) lines accumulated > 90%
      gamma-tocopherol. We identified and isolated two gamma-TMT paralogs (gamma-TMT-1
      and gamma-TMT-2). Both mapped to linkage group 8, cosegregated with the g locus,
      and were transcribed in developing seeds of wildtype lines. The g mutation
      greatly decreased gamma-TMT-1 transcription, caused alternative splicing of gamma
      TMT-1, disrupted gamma-TMT-2 transcription, and knocked out one of two
      transcription initiation sites identified in the wildtype; gamma-TMT
      transcription was 36 to 51-fold greater in developing seeds of wildtype (g(+)
      g(+)) than mutant (g g) lines. F(2) populations (B109 x LG24 and R112 x LG24)
      developed for mapping the g locus segregated for a previously unidentified locus
      (d). B109, R112, and LG24 were homozygous for a null mutation (m = Tph(1)) in MT
      1, one of two 2-methyl-6-phytyl-1,4-benzoquinone/2-methyl-6-solanyl-1,4
      benzoquinone methyltransferase (MPBQ/MSBQ-MT) paralogs identified in sunflower.
      The d mutations segregating in B109 x LG24 and R112 x LG24 were allelic to a
      cryptic mutation identified in the other MPBQ/MSBQ-MT paralog (MT-2) and
      disrupted the synthesis of alpha- and gamma-tocopherol in F(2) progeny carrying m
      or g mutations--m m g(+) g(+) d d homozygotes accumulated 41.5% alpha- and 58.5%
      beta-T, whereas m m g g d d homozygotes accumulated 58.1% gamma- and 41.9% delta
      T. MT-2 cosegregated with d and mapped to linkage group 4. Hence, novel
      tocopherol profiles are produced in sunflower seed oil by three non-allelic
      epistatically interacting methyltransferase mutations.

PMID- 16896720
TI  - Histomorphological evidence of muscle tissue damage and recording area using
      coiled and straight intramuscular wire electrodes.
AB  - While intramuscular wire electrodes (IWE) for the measurement of neuromuscular
      function offer high spatial resolution for examining single motor unit activity,
      the resulting damage to muscle tissue and mechanical instability should be
      considered. We examined the influence of IWE type and component parts on muscle
      damage using light microscopy in rats and confirmed that intramuscular pressure
      influences the mechanical stability of IWE. Three types of electrode, coiled
      electrodes with or without suture material inside and a straight electrode, were
      inserted into the soleus, gastrocnemius and tibialis anterior muscles. Transverse
      serial sections (5 microm) of these muscles in the vicinity of the electrodes
      were stained with haematoxylin and eosin. Less structural damage was observed in
      the vicinity of the recording points (leading-off surface; 50 microm diameter)
      for all electrode types compared to the electrode body. No differences in the
      extent of tissue damage were observed around the recording points for all
      electrodes. However, compared to straight electrodes, the extent of damaged
      tissue around the bodies of coiled electrodes was significantly (P < 0.0001)
      greater. The average distance between the recording points and the electrode body
      was <1 mm for all electrodes. Intramuscular pressure at rest and maximal twitch
      contraction were 1.1 +/- 0.5 and 49.4 +/- 4.0 mmHg, respectively. Coiled IWEs
      became well integrated with muscle fibres, stabilizing electrode localization and
      facilitating electromyographic recordings without causing significant muscle
      damage.

PMID- 16896721
TI  - A comparative scale of autonomic function with age through the tone-entropy
      analysis on heart period variation.
AB  - Tremendous numbers of heart rate variability studies have aimed to elucidate age
      associated alterations of autonomic function in the past decades. However, the
      studies, far from clarifying ageing mechanisms, fell into confusion by a lack of
      common scales. The purpose of this study is to show a possibility to establish a
      comparative scale of autonomic function through a method, tone-entropy (T-E)
      analysis on heart period variation, whose validity has been already examined on
      typical physiological cases (Oida et al. in J Appl Physiol 82:1794-1801, 1997;
      Oida et al. in J Gerontol 54A:M219-M224, 1999a; Oida et al. in Acta Physiol Scand
      165:129-134, 1999b; Oida et al. in Acta Physiol Scand 165:421-422, 1999c; Amano
      et al. in Eur J Appl Physiol 94:602-610, 2005). In this study, 276 subjects from
      teens to seventies were examined at rest by T-E analysis together with
      conventional time and frequency domain analyses. The tone (negativity represents
      vagal predominance) became significantly high [-0.174 +/- 0.026 (teens) to -0.024
      +/- 0.004 (seventies), P < 0.05 for one-way ANOVA], and the entropy (total
      autonomic activity), significantly low [4.40 +/- 0.12 (teens) to 2.90 +/- 0.09
      bit (seventies), P < 0.05] with advancing age. The result, plotted in 2-D T-E
      space, showed that the ageing traced a curvi-linear relation from right-bottom to
      left-top, and was consistent with previously studied typical physiological cases.
      The conventional analyses showed almost the same autonomic reduction as T-E did,
      but failed in detecting delicate alteration of autonomic balance. The results,
      showing that autonomic activity reduced in both pathways impairing vagal
      predominance significantly with ageing, suggested a possibility to assess
      autonomic function in 2-D T-E space in a comparative way.

PMID- 16896722
TI  - Response of antioxidant defences to oxidative stress induced by prolonged
      exercise: antioxidant enzyme gene expression in lymphocytes.
AB  - The response of lymphocyte and plasma antioxidant defences to a prolonged
      exercise as a cycling stage in a professional race was analysed. Antioxidant
      enzyme activities and gene expression, carbonyl derivative and MDA levels were
      determined in lymphocytes. Plasma levels of vitamin E, carotenes, protein
      carbonyl derivatives and the test d-Roms were measured. Significant increases in
      plasmatic carbonyls and in the test d-Roms were observed after the cycling stage.
      No significant differences were found in the lymphocyte MDA and carbonyl
      derivative levels. A significant increase was found in plasma vitamin E
      concentration after the cycling stage; however, the lymphocyte vitamin E
      concentration did not change. Significant increases were observed in lymphocyte
      total superoxide dismutase (SOD) activity and in the levels of CuZn-SOD and Mn
      SOD isoenzymes. The moderate levels of oxidative stress in the lymphocyte induced
      a cellular adaptation to exercise enough to counteract the negative effects of
      oxidative stress.

PMID- 16896723
TI  - The effect of acute exercise on endothelial function following a high-fat meal.
AB  - The transient impairment of endothelial function following a high-fat meal is
      well established. Brachial artery flow-mediated dilation (FMD) decreases between
      2 and 6 h post ingestion. Whether this impairment can be reduced with acute
      aerobic exercise has not been investigated. The purpose of this study was to
      investigate if a single sustained aerobic exercise session can counteract the
      postprandial attenuation in brachial artery FMD associated with the ingestion of
      a high-fat meal. Eight apparently healthy adults (five men, three women), age
      25.5 +/- 0.8 years, performed three treatment conditions in a counter-balanced
      design: (1) low-fat meal alone (LFM), (2) high-fat meal alone (HFM), and (3) one
      session of aerobic exercise presented 2 h after ingesting a high-fat meal (HFM
      EX). The examination of brachial artery FMD was performed at baseline and 4 h
      following the ingestion of the meal for each treatment condition. A 3 x 2
      (treatment x time) repeated measures ANOVA exhibited a significant interaction (P
      = 0.019). Preprandial FMDs were similar (P = 0.863) among all three treatment
      conditions. The FMDs following the LFM (7.18 +/- 1.31%) and HFM-EX (8.72 +/-
      0.94%) were significantly higher (P = 0.001) than the FMD following the HFM (4.29
      +/- 1.64%). FMD was significantly elevated above preprandial values following the
      HFM-EX (5.61 +/- 1.54 to 8.72 +/- 0.94%, P = 0.005) but was unchanged following
      the LFM (6.17 +/- 0.94 to 7.18 +/- 1.31%, P = 0.317) and the HFM (5.73 +/- 1.23
      to 4.29 +/- 1.64%, P = 0.160). These findings suggest that a single aerobic
      exercise session cannot only counteract the postprandial endothelial dysfunction
      induced by the ingestion of a high-fat meal, but also increase brachial artery
      FMD in apparently healthy adults.

PMID- 16896725
TI  - Vagal postganglionic origin of vasoactive intestinal polypeptide (VIP) mediating
      the vagal tachycardia.
AB  - Our aim was to confirm the role of postganglionic vagal fibres and vasoactive
      intestinal polypeptide (VIP) in mediating the vagal tachycardia in anaesthetised
      dogs. Vagal postganglionic stimulation after atenolol (1 mg/kg) and hexamethonium
      (10 mg/kg) caused a bradycardia (40 beats/min, n = 2), after atropine (0.5 mg/kg
      i.v.) the resulting tachycardia (37 beats/min) was attenuated by VIP receptor
      antagonism with VIP (6-28) (100 mug i.c.) by approximately 50%. VIP release from
      vagal postganglionic fibres mediates the vagal tachycardia.

PMID- 16896724
TI  - Effect of multiple oral doses of androgenic anabolic steroids on endurance
      performance and serum indices of physical stress in healthy male subjects.
AB  - Anabolic androgenic steroids (AAS) are doping agents that are mostly used for
      improvement of strength and muscle hypertrophy. In some sports, athletes reported
      that the intake of AAS is associated with a better recovery, a higher training
      load capacity and therefore an increase in physical and mental performances. The
      purpose of this study was to evaluate, the effect of multiple doses of AAS on
      different physiological parameters that could indirectly relate the physical
      state of athletes during a hard endurance training program. In a double blind
      settings, three groups (n = 9, 8 and 8) were orally administered placebo,
      testosterone undecanoate or 19-norandrostenedione, 12 times during 1 month. Serum
      biomarkers (creatine kinase, ASAT and urea), serum hormone profiles
      (testosterone, cortisol and LH) and urinary catecholamines (noradrenalin,
      adrenalin and dopamine) were evaluated during the treatment. Running performance
      was assessed before and after the intervention phase by means of a standardized
      treadmill test. None of the measured biochemical variables showed significant
      impact of AAS on physical stress level. Data from exercise testing on submaximal
      and maximal level did not reveal any performance differences between the three
      groups or their response to the treatment. In the present study, no effect of
      multiple oral doses of AAS on endurance performance or bioserum recovery markers
      was found.

PMID- 16896726
TI  - Role of Hsp72 and norepinephrine in the moderate exercise-induced stimulation of
      neutrophils' microbicide capacity.
AB  - The influence of a single session of moderate exercise (45 min at 55% of VO(2
      )max) performed by young sedentary men (23-25 years old) on the microbicidal
      capacity of neutrophils was compared by using both direct (killing of
      phagocytosed Candida albicans) and indirect (superoxide anion production measured
      by NBT reduction) techniques. In addition, the role of norepinephrine and heat
      shock protein (Hsp) 72 in the modulation of microbicide capacity of neutrophils
      was evaluated during the protocol of exercise and recovery period (24 h). No
      significant changes were found in the superoxide production after exercise.
      However, immediately after exercise there was an increase in the destruction of
      C. albicans, which remained higher than basal values 1 day later. This behaviour
      was similar to the changes found in the serum extracellular Hsp72 concentrations
      (an increase after exercise that remained higher than basal values 24 h later).
      In vitro, the raised physiological concentration of Hsp72 after exercise also
      increased the microbicide capacity of neutrophils with respect to controls and
      the values induced by the basal concentration of the protein. This indicates that
      Hsp72 is participating as a "stress mediator" of the stimulated microbicide
      activity during moderate exercise. However, norepinephrine is not mediating the
      increased killing of C. albicans during exercise.

PMID- 16896727
TI  - Creatine supplementation does not enhance submaximal aerobic training adaptations
      in healthy young men and women.
AB  - The benefits of dietary creatine supplementation on muscle performance are
      generally related to an increase in muscle phosphocreatine content. However,
      creatine supplementation may benefit endurance sports through increased glycogen
      re-synthesis following exercise. This study investigated the effect of creatine
      supplementation on muscle glycogen content, submaximal exercise fuel utilisation
      and endurance performance following 4 weeks of endurance training. Thirteen
      healthy, physically active, non-vegetarian subjects volunteered to take part and
      completed the study. Subjects were supplemented with either creatine monohydrate
      (CREAT, n = 7) or placebo-maltodextrin (CON, n = 6). Submaximal fuel utilisation
      and endurance performance were assessed before and after a 4 week endurance
      training program. Muscle biopsies were also collected before and following
      training for assessment of muscle creatine and glycogen content. Training
      increased quadriceps glycogen content to the same degree (approximately 20%) in
      both groups (P = 0.04). There was a significant training effect on submaximal
      fuel utilisation and improved endurance performance. However, there was no
      significant treatment effect of creatine supplementation. Creatine
      supplementation does not effect metabolic adaptations to endurance training.

PMID- 16896729
TI  - Indicators of maximal hiking performance in Laser sailors.
AB  - Laser class sailors have to hike out, i.e. hook their feet under the toe straps
      near the centreline of the boat and hold their upper bodies over the edge of the
      boat, to counteract the heeling forces generated by the sails. To identify the
      parameters that are associated with maximal hiking performance, this cross
      sectional observational study measures various knee extensor and hip flexor
      muscle performance characteristics in 55 Laser sailors and correlates each with
      the area-under-the-curve hiking moment over 3 min of hiking on a hiking
      dynamometer (HM180). Our results showed that higher body mass and HM180 were
      significantly associated with better race scores (Spearman's rho = - 0.69 and -
      0.62, respectively, both P < 0.01) in male sailors who participated in the
      National Inter-School Laser competition. Body mass (Pearson's correlation
      coefficient, r > or = 0.95, P < 0.01 in both males and females), maximum
      voluntary isometric strength of the quadriceps (r > or = 0.80, P < 0.01 in both
      males and females), and 3-RM knee extension strength (r > or = 0.80, P < 0.01 in
      both males and females) were associated with a higher HM180. The correlations
      between height, abdominal muscle endurance (crunches), explosive lower body
      strength (vertical jumps), cycling time-to-exhaustion, quadriceps strength
      endurance, or isometric quadriceps endurance with incremental loads (bucket
      test), and HM180 were weaker (r < 0.60). HM180 may be a useful performance
      indicator for Laser racing. Since strength measures correlated well with HM180,
      greater emphasis should be placed on developing maximum strength in the
      quadriceps to improve maximal hiking performance.

PMID- 16896728
TI  - The reorganization of tremulous movements in the upper limb due to finger
      tracking maneuvers.
AB  - In light of the interplay between limb oscillatory outputs and the outcome
      performance of movement effectors, this study was undertaken to investigate
      neuromotor control in the upper limb during position tracking and posture
      holding. Sixteen volunteers conducted a postural pointing task and two index
      tracking maneuvers at 0.3 and 0.6 Hz with an outstretched arm. Limb acceleration
      in the index finger, hand, forearm, arm, and C7 spinal process were monitored to
      correlate functionally with the accuracy of index rhythmic displacements. The
      results showed that index oscillatory activity multiplied with tracking speed,
      but hand oscillatory activity declined during tracking movement. The tracking
      maneuvers also altered spectral distribution of the tremulous activities in the
      context of a lower spectral peak in the range of 8-12 Hz and suppression of
      spectral peaks at 2-4 Hz, in reference to that already presented in posture
      tremor. Consisting of three local maxima around 2-4, 8-12, and 18-22 Hz, the
      coherence of tremulous activity between the finger and hand during position
      tracking was nearly identical, but inferior to high coherence below 12 Hz during
      posture holding. Functionally, better tracking performance was associated with a
      smaller tremulous activity in the finger and hand, entailing sophisticated
      release of mechanical couplings in the finger-hand and hand-forearm. In
      conclusion, inversely related to tracking performance, limb tremulous movements
      were task-dependently organized, and speed-invariant coherence of limb tremulous
      movement specified an inter-segmental coordination, which is physiological
      evidence of the generalized motor program for position tracking.

PMID- 16896730
TI  - Effect of single-leg resistance exercise on regional arterial stiffness.
AB  - To examine the effects of lower-limb unilateral resistance exercise on central
      and peripheral arterial stiffness, thirteen participants (7 male and 6 female,
      mean age = 21.5 +/- 0.7 years) performed leg press exercise using their dominant
      leg. Pulse wave velocity (PWV) was used to measure central (carotid to femoral)
      and peripheral (femoral to dorsalis pedis of both legs) arterial stiffness
      before, 5 min post, and 25 min post exercise. No change was found in central PWV.
      A leg-by-time interaction was found as peripheral PWV in the non-exercised leg
      did not change (7.9 +/- 0.3 m/s to 7.9 +/- 0.3 m/s to 8.0 +/- 0.3 m/s, P = 0.907)
      while peripheral PWV in the exercised leg significantly decreased from pre (8.7
      +/- 0.4 m/s) to 5 min post exercise (7.5 +/- 0.3 m/s, P = 0.008) and 25 min post
      exercise (7.8 +/- 0.3 m/s, P = 0.031). Systolic blood pressure (BP) increased
      significantly from pre (126.9 +/- 3.4 mmHg) to 5 min post exercise (133.7 +/- 4.3
      mmHg, P = 0.023) and was not different than resting values 25 min post exercise
      (123.2 +/- 3.1 mmHg). There was no change in diastolic BP. Compared to heart rate
      (HR) pre-exercise (55.4 +/- 1.4 bpm), HR was significantly increased 5 min post
      exercise (70.7 +/- 3.0 bpm, P = 0.001) and 25 min post exercise (69.1 +/- 2.0, P
      = 0.001). Acute resistance exercise appears to decrease arterial stiffness in the
      exercised leg while having no effect on central arterial stiffness or arterial
      stiffness of the non-exercised leg. These findings suggest that regional changes
      rather than systemic alterations may influence arterial stiffness following acute
      resistance exercise.

PMID- 16896731
TI  - Effect of equitation training on health and physical fitness of college females.
AB  - Limited information exists concerning equitation as a viable form of physical
      activity. The study's purpose was to quantify effects of an equitation training
      program on health and physical fitness of college females. Following written
      informed consent, 15 college females enrolled in equitation and 10 controls (age
      = 23.6 +/- 2.5 years; ht = 165.3 +/- 5.3 cm; wt = 62.4 +/- 3.4 kg) underwent a
      comprehensive pre- and post-series of tests to assess cardiorespiratory response
      (Bruce; VO2(peak), HR(peak), VE(peak), RER(peak), MAP(peak), RPP(peak)), body
      composition (body mass, body fat, fat-free mass), muscular power [Wingate; peak
      and mean power (MP), total power output, fatigue index (FI)], muscular strength
      (curl-ups, reverse sit-ups, pushups, handgrip), blood chemistry, and coronary
      risk. The equitation group trained at various equine gaits for 14 weeks, 5
      days/week. Multivariate analyses of variance (Wilks' Lambda) indicated a
      significant main effect of training across muscular power (F (4,25) = 3.965; P =
      0.013), but not across cardiorespiratory response (F (11,18) = 1.472; P = 0.225),
      body composition (F (3,26) = 1.081; P = 0.375), or muscular strength (F (4,25) =
      2.172; P = 0.102). Pre-post improvements in MP (+13.3%; P = 0.01), total work
      output (+11.8%; P = 0.015), and FI (-10.5%; P = 0.038) were observed.
      Nonsignificant improvements of 8.5-11.4% were observed in muscular strength and
      body composition. In conclusion, equitation does not provide an adequate stimulus
      to improve health and fitness in young adults. Individuals who participate in
      equitation need to supplement this activity with traditional aerobic and load
      bearing training regimens.

PMID- 16896732
TI  - Post-resistance exercise hypotension, hemodynamics, and heart rate variability:
      influence of exercise intensity.
AB  - The occurrence of post-exercise hypotension after resistance exercise is
      controversial, and its mechanisms are unknown. To evaluate the effect of
      different resistance exercise intensities on post-exercise blood pressure (BP),
      and hemodynamic and autonomic mechanisms, 17 normotensives underwent three
      experimental sessions: control (C-40 min of rest), low- (E40%-40% of 1 repetition
      maximum, RM), and high-intensity (E80%-80% of 1 RM) resistance exercises. Before
      and after interventions, BP, heart rate (HR), and cardiac output (CO) were
      measured. Autonomic regulation was evaluated by normalized low- (LF(R-R)nu) and
      high-frequency (HF(R-R)nu) components of the R-R variability. In comparison with
      pre-exercise, systolic BP decreased similarly in the E40% and E80% (-6 +/- 1 and 
      8 +/- 1 mmHg, P < 0.05). Diastolic BP decreased in the E40%, increased in the C,
      and did not change in the E80%. CO decreased similarly in all the sessions (-0.4
      +/- 0.2 l/min, P < 0.05), while systemic vascular resistance (SVR) increased in
      the C, did not change in the E40%, and increased in the E80%. Stroke volume
      decreased, while HR increased after both exercises, and these changes were
      greater in the E80% (-11 +/- 2 vs. -17 +/- 2 ml/beat, and +17 +/- 2 vs. +21 +/- 2
      bpm, P < 0.05). LF(R-R)nu increased, while ln HF(R-R)nu decreased in both
      exercise sessions. IN CONCLUSION: Low- and high-intensity resistance exercises
      cause systolic post-exercise hypotension; however, only low-intensity exercise
      decreases diastolic BP. BP fall is due to CO decrease that is not compensated by
      SVR increase. BP fall is accompanied by HR increase due to an increase in
      sympathetic modulation to the heart.

PMID- 16896734
TI  - Accuracy and reliability of the ParvoMedics TrueOne 2400 and MedGraphics VO2000
      metabolic systems.
AB  - This study examined the accuracy and reliability of the MedGraphics VO2000
      (VO2000) portable metabolic system and the ParvoMedics TrueOne 2400 (TrueOne
      2400) metabolic cart against the criterion Douglas bag (DB) method. Ten healthy
      males (age 20 +/- 1.7 years) had their gas exchange variables measured at rest
      and during cycling at 50, 100, 150, 200, and 250 W. Each stage was 10-12 min. For
      half of the stage gas exchange was measured with the DB and TrueOne 2400
      simultaneously and for the other half of the stage gas exchange was measured with
      the VO2000. The testing was performed on two separate days and the order in which
      the equipment was used in each stage was randomized. Reliability between days for
      V (E) (CV 7.3-8.8%) was similar among devices, however, for VO2, and VCO2 the
      VO2000 (CV 14.2-15.8%) was less reliable compared to the DB (CV 5.3-6.0%) and
      TrueOne 2400 (CV 4.7-5.7%). The TrueOne 2400 was not significantly different from
      the DB at rest or any work rate for V (E), VO2, or VCO2 (P > or = 0.05). The
      VO2000 was significantly different from the DB for V (E) at 50-100 W, VO2 at rest
      and 100-250 W, and VCO2 at rest and 200-250 W (all, P < 0.05). The TrueOne 2400
      provides accurate and reliable results for the measurement of gas exchange
      variables. The VO2000 portable metabolic system was less reliable for measuring
      VO2 and VCO2 and generally overestimates VO2 at most cycling work rates. Further
      research is needed to confirm the results found with the VO2000.

PMID- 16896735
TI  - Adaptations to long-term strength training of ankle joint muscles in old age.
AB  - The aim of this study was to enquire whether older adults, who continue plantar
      flexion (PF) strength training for an additional 6-month period, would achieve
      further improvements in neuromuscular performance, in the ankle PFs, and in the
      antagonist dorsi-flexors (DFs). Twenty-three healthy older volunteers (mean age
      77.4 +/- 3.7 years) took part in this investigation and 12 of them followed a 1
      year strength-training program. Both neural and muscular factors were examined
      during isometric maximal voluntary contraction (MVC) torques in ankle PF and DF
      pre-training, post 6 and post 12 months. The main finding was that 6 months of
      additional strength training of the PFs, beyond 6 months, allowed further
      improvements in neuromuscular performance at the ankle joint in older adults.
      Indeed, during the first 6 months of progressive resistance training, there was
      an increase in the PF MVC torque of 11.1 +/- 19.9 N m, and then of 11.1 +/- 17.9
      N m in the last 6-month period. However, it was only after 1 year that there was
      an improvement in the evoked contraction at rest in PF (+ 8%). The strength
      training of the agonist PF muscles appeared to have an impact on the maximal
      resultant torque in DF. However, it appeared that this gain was first due to
      modifications occurring in the trained PFs muscles, then, it seemed that the
      motor drive of the DFs per se was altered. In conclusion, long-term strength
      training of the PFs resulted in continued improvements in neuromuscular
      performance at the ankle joint in older adults, beyond the initial 6 months.

PMID- 16896733
TI  - The denervated muscle: facts and hypotheses. A historical review.
AB  - Denervation changes in skeletal muscle (atrophy; alterations of myofibrillar
      expression, muscle membrane electrical properties, ACh sensitivity and excitation
      contraction coupling process; fibrillation), and their possible causes are
      reviewed. All changes can be counteracted by muscle electrostimulation, while
      denervation-like effects can be caused by the complete conduction block in muscle
      nerve. These results do not support the hypothesis that the lack of neurotrophic,
      non-motor factors plays a role in denervation phenomena. Instead they support the
      view that the lack of neuromotor discharge is the only cause of the phenomena and
      that neuromotor activity is an essential factor in regulating muscle properties.
      However, some experimental results cannot apparently be explained by the lack of
      neuromotor impulses, and may still suggest that neurotrophic influences exist. A
      hypothesis is that neurotrophic factors, too feeble to maintain a role in
      completely differentiated, adult muscles, can concur with neuromotor activity in
      the differentiation of immature, developing muscles.

PMID- 16896736
TI  - Motor performance changes induced by muscle vibration.
AB  - The possibility that mechanical stimulation of selected muscles can act directly
      on the nervous system inducing persistent changes of motor performances was
      explored. On the basis of literature, stimulating parameters were chosen to
      stimulate the central nervous system and to avoid muscle fibre injuries. A
      sinusoidal mechanical vibration was applied, for three consecutive days, on the
      quadriceps muscle in seven subjects that performed a muscular contraction (VC).
      The same stimulation paradigm was applied on seven subjects in relaxed muscle
      condition (VR) and seven subjects were not treated at all (NV). Two sessions (PRE
      and POST) of isometric and isotonic tests were performed separated for 21 days,
      in all studied groups 7 days before and 15 days after stimulation, whilst an
      isokinetic test was performed on VC only. In the isometric test, the time of
      force development showed a significant decrease only in VC (POST vs PRE mean
      27.8%, P < 0.05). In the isotonic test, the subjects' had to perform a fatiguing
      leg extension against a load. In this condition, the fatigue resistance increased
      greatly in VC (mean 40.3%, P < 0.001), increased slightly in VR and there was no
      difference in NV. In Isokinetic test, at several angular velocities,
      significantly less time was required to reach the force peak (mean 20.2% P <
      0.05). The findings could be ascribed to plastic changes in proprioceptive
      processing, leading to an improvement in knee joint control. Such action
      delineates a new tool in sports training and in motor rehabilitation.

PMID- 16896737
TI  - Body cooling attenuates the decrease in maximal oxygen uptake associated with
      cardiovascular drift during heat stress.
AB  - Previous research suggests cardiovascular drift (CV drift) is associated with
      decreased maximal oxygen uptake (VO(2)(max)) during heat stress, but more
      research manipulating CV drift with subsequent measurement of VO(2)(max) is
      needed to assess whether this relationship is causal. To assess causation,
      VO(2)(max) was measured during the same time interval that CV drift occurred
      (between 15 and 45 min of submaximal exercise under different conditions of body
      cooling intended to manipulate CV drift). Ten men completed a control graded
      exercise test (GXT) in 22 degrees C to measure VO(2)(max) then on separate
      occasions they cycled in 35 degrees C at 60% VO(2)(max) for 15 min (15 max), 45
      min with no cooling (NC), and 45 min with fan airflow (FAN) beginning at
      approximately 18 min into exercise, and each bout was immediately followed by a
      GXT to measure VO(2)(max) In NC, VO(2)(max) decreased 18%, heart rate (HR)
      increased 16%, and stroke volume (SV) fell 12% (P < 0.05) from min 15 to min 45.
      In FAN, VO(2)(max) fell less (5.7%, P < 0.05) , HR rose less (4%, P < 0.05) and
      SV decreased less (3%, P < 0.05) from 15 to 45 min. The fall in VO(2)(max)
      associated with CV drift during exercise in a hot environment is attenuated with
      body cooling via fan airflow. The findings support the notion that a causal link
      exists between CV drift that occurs during prolonged exercise in a hot
      environment and a decrease in VO(2)(max).

PMID- 16896738
TI  - Effects of low and high levels of moderate hypoxia on anaerobic energy release
      during supramaximal cycle exercise.
AB  - The purpose of this study was to investigate whether hypoxia can alter anaerobic
      energy release during supramaximal exercise. Seven male subjects performed 12
      submaximal cycling tests to establish the relationship between workload and O2
      demand. The subjects also performed 40 s Wingate tests (WT) under normoxia (room
      air), two levels of moderate hypoxia of 16.4% O2 and 12.7% O2. We measured the
      power output and oxygen uptake (VO2) during each test and estimated the O2
      demand, O2 deficit and percentage of anaerobic energy release (%AnAER). These
      data were analyzed for each 20 s interval. At all intervals, there were no
      differences in Pmean per body mass (BM)(-1), O2 demand per BM(-1) or O2 deficit
      per BM(-1) among the three O2 conditions. However, under hypoxia of 12.7%, VO2
      per BM(-1) was significantly decreased and %AnAER was significantly increased in
      the late phase (20-40 s) of the WT, compared to normoxia (P<0.05). There were no
      such significant differences between normoxia and hypoxia of 16.4%. Thus, the
      present results show that the degree of hypoxia affects the magnitude of the
      hypoxia-induced increase in anaerobic energy release in the late phase of the WT
      and suggest that certain degrees of hypoxia induce significant increases in the
      amount of anaerobic energy released, compared to normoxia.

PMID- 16896739
TI  - Polylactide (LTS) causes less inflammation response than polydioxanone (PDS): a
      meniscus repair model in sheep.
AB  - BACKGROUND: Incidence of meniscus injury has increased in today's active society.
      Arthroscopical refixation yields better results than partial meniscectomy. The
      best healing rates are achieved by sutures. As non-degradable sutures are
      permanent foreign bodies, slow absorbable materials are needed. A slow degradable
      suture with high concentration of polylactide acid, the so-called "long-term
      suture" (LTS, Panacryl), has been suggested to produce a higher inflammatory
      response than conventional polymer sutures [Vicryl, Dexon or polydioxanone
      (PDS)]. The aim of the study was to assess LTS for meniscus repair after a
      traumatic lesion and to evaluate immunological response, biodegradation and
      healing. METHODS: In 24 randomised sheep, a radial tear of the medial meniscus
      was sutured by either PDS or LTS. Twelve sham-operated animals served as control.
      Half of the sheep were killed after 6 months, the other half after 12 months. The
      medial and lateral meniscus, synovial membrane, articular cartilage and ascendant
      lymph nodes up to the kidney were examined. Joint effusion was evaluated by MRI.
      RESULTS: The synovial membrane was significantly thinner in the LTS group (6
      months 85 +/- 10 microm, 1 year 100 +/- 28 microm) than in the PDS group (6
      months 165 +/- 10 microm, 1 year 175 +/- 23 microm, P < 0.001) and the controls
      (6 months 150 +/- 17 microm, 12 months 192 +/- 21 microm, P < 0.001). The joint
      effusion was higher in the PDS than in the LTS group after 6 months, and tended
      to be higher in controls. In controls, effusion tended to be higher than in the
      LTS group. In all medial departments, osteoarthritis evolved much more intensely
      than in the lateral knee departments (P < 0.01). Bilateral lymph nodes from the
      groin up to the kidneys were larger (crosscut area) after 6 months in the
      controls (2.28 +/- 0.7 mm(2)) and PDS treated animals (2.3 +/- 0.7 mm(2)) than in
      the LTS group (1.3 +/- 0.3 mm(2), P < 0.001). After 1 year, node size differed
      significantly between controls and animals from the LTS group (1.98 +/- 0.4 mm(2)
      vs. 1.5 +/- 0.2 mm(2), P < 0.05), and between animals from the PDS and the LTS
      group (2.5 +/- 0.1 mm(2) vs. 1.5 +/- 0.2 mm(2), P < 0.001). CONCLUSION: The
      polylactide thread LTS causes less immunological reaction and synovitis than a
      polydioxanone suture (PDS). CLINICAL RELEVANCE: LTS may serve as an alternative
      to PDS for repair of slow healing structures such as tendons and menisci.

PMID- 16896740
TI  - The effect of bone tunnel dilation versus extraction drilling on the initial
      fixation strength of press-fit anterior cruciate ligament reconstruction.
AB  - INTRODUCTION: Serial dilation of the bone tunnel has been reported to create a
      tighter graft-tunnel fit. It was hypothesized that a serial dilation of the
      femoral bone tunnel would increase the initial fixation strength in press-fit
      anterior cruciate ligament (ACL) reconstructive surgery. MATERIALS AND METHODS:
      Initial fixation strength of the femoral press-fit fixation technique was
      investigated in 72 porcine specimens in an ex vivo study by varying the femoral
      tunnel preparation technique. Extraction-drilling, tunnel dilation by 1 mm and
      dilation by 2.5 mm were assessed. Initial fixation strength of press-fit fixated
      patellar tendon-bone grafts was tested within each preparation group conducting a
      single cycle (and cyclic) load to failure protocol. The resulting tunnel diameter
      and the porcine femoral bone mineral density were determined using
      microradiographs and peripheral quantitative CT scans, respectively. RESULTS:
      Dilating a previously extraction-drilled femoral bone tunnel by 1 mm
      significantly enhances initial press-fit fixation strength in both single cycle
      and cyclic load to failure testing when compared to extraction-drilling and
      tunnel dilation by 2.5 mm. Due to an initial spring-back effect the resulting
      diameter of the femoral tunnel was underestimated by 3.3% with drilling and 6.7
      and 12.2% with dilation by 1 and 2.5 mm, respectively. Volumetric trabecular bone
      mineral density at the site corresponding to the area of tunnel placement
      averaged 318 mg/cm(3). CONCLUSION: Dilating a femoral tunnel that is underdrilled
      by 1 mm appears to be a reasonable technical procedure in order to enhance
      initial fixation strength of press-fit ACL graft fixation.

PMID- 16896741
TI  - Repair of articular cartilage lesions in aged chickens by allogeneic
      transplantation of fresh embryonic epiphyses.
AB  - INTRODUCTION: The potential of fresh whole chick epiphyses of embryonic origin to
      serve as implant material for cartilage defects of aged chicken was tested.
      MATERIALS AND METHODS: Fresh epiphyses of 11-day-old embryos were collected from
      24 animals and transplanted into defects created in the weight-bearing areas of
      tibiotarsal joint cartilage of 2-year-old chicks. Upon sacrifice, samples were
      examined macroscopically and microsections were prepared for histology. RESULTS:
      Macroscopically, control defects remained empty at all the time intervals.
      Defects of the experimental group were, on the other hand, filled with
      cartilaginous tissue as early as 2 weeks posttransplantation, although individual
      epiphyses could still be noted in the implant tissue. At 4 weeks and later,
      defects were filled with cartilaginous material indistinguishable from hyaline
      cartilage. Histologically, all grafts remained within the defect's pits, showing
      mitotic and metabolic activity typical to proliferating hyaline cartilage. The
      engrafted epiphyses showed a partial incorporation and integration with the
      surrounding host tissues already at 2 weeks. At 4 weeks and later, the
      integration was complete. CONCLUSIONS: It is concluded that a chick embryonic
      epiphyseal cartilage is suitable as a graft source for articular cartilage
      transplantation. The embryonic epiphyses provide immediate inherent stability to
      the graft and supply a good mix of mesenchymal progenitor cells responsible for
      the high rate of cell proliferation and adhesion to the differentiated committed
      chondrocytes of the host that create the typical favorable chondrogenic milieu.
      Based on the present findings, it is postulated that human embryonic epiphyses
      may, in the future, represent an alternative source to the commonly used
      techniques of hyaline cartilage repair.

PMID- 16896742
TI  - Conservative treatment of an acute compartment syndrome of the thigh.
AB  - Compartment syndromes of the thigh after blunt trauma without any fracture are
      rare. Most surgeons recommend operative treatment. There are different rules for
      compartment syndromes of the thigh in young athletes after blunt trauma compared
      to compartment syndromes at other locations [(1) the large volume of the
      quadriceps muscle, (2) its relatively elastic fascia, (3) the direct proximal
      contact to the hip muscles which allows extravasation of fluid out of the
      compartment)]. We present a case of conservative treatment of elevated intra
      compartmental pressure (ICP) of the anterior thigh after blunt trauma and the
      follow-up until return to sport. Conservative treatment of a compartment syndrome
      of the thigh after blunt trauma in a young patient without fracture or vascular
      damage was successful without short-term sequelae. Recovery of muscle strength is
      delayed but return to sport is possible. Depending on the severity the diagnosis
      and follow-up with ICP measurements and MRI is necessary. There is a very good
      chance for excellent outcome without any risk of surgery. However, a long healing
      time is possible.

PMID- 16896743
TI  - Reconstruction of the coronoid process with iliac crest bone graft in complex
      fracture-dislocation of elbow.
AB  - A 36-year-old man sustained posterior dislocation of left elbow joint with
      olecranon fracture, comminuted coronoid fracture and subluxation of proximal
      radioulnar joint. We reconstructed the coronoid process with autogenous iliac
      crest bone graft and reduced the olecranon fracture with internal fixation. In
      addition, we also repaired the medial collateral ligament, annular ligament and
      anterior capsule during the operation. He received immobilization of the left
      elbow for 3 weeks after surgery and started range of motion exercises. The
      radiographic bone union was found 2 months after operation. The range of motion
      of the elbow was full at 12 months after operation. The latest 2-year follow-up,
      the functional result of the elbow was excellent.

PMID- 16896744
TI  - Comparison of outcomes of two different surgeries in regarding to complications
      for chronic anterior shoulder instability.
AB  - INTRODUCTION: The purpose of this study is to compare the early clinical results
      of two techniques in regarding to complications in the patients who suffered from
      chronic anterior traumatic isolated shoulder instability. METHOD: Eighty-five
      patients underwent reconstructive procedures due to chronic isolated traumatic
      shoulder instability in our clinic between 1990 and 2002. Sixty-four patients in
      whom preoperatively Bankart lesion were detected with MRI and who participated in
      the regular follow-up were included in the study. Thirty-four patients were
      treated with Bankart repair (Group I) and 30 patients were treated with Modified
      Bristow procedure (Group II). Mean follow-up period was 25 (24-39) months for
      group I and 28 (24-96) months for group II. All cases were evaluated
      preoperatively and postoperatively according to Rowe scoring system. RESULTS:
      Mean Rowe scores were 90 and 88.1 for group I and II, respectively. Due to
      recurrent dislocation, four revision surgeries (one in group I, three in group
      II) were performed. Surgical complications were encountered in group II, just as
      fracture at the bone block in four cases, nonunion in five cases and removal of
      loose screw in one case. DISCUSSION: According to clinical outcomes, both the
      techniques are useful and feasible for the treatment of the chronic traumatic
      isolated anterior shoulder instability; however, complication rate is higher in
      the Modified Bristow technique and, Bankart repair is directed to the anatomic
      repair of the original pathology.

PMID- 16896745
TI  - First results with the trochanter fixation nail (TFN): a report on 120 cases.
AB  - A complication rate between 4-18% for the conventional osteosynthesis of the
      proximal femur fracture continues to be unacceptable even if increasing age and
      co-morbidity of patients are taken into account. Therefore, new intramedullary
      techniques are under development, and we here report our results with the novel
      trochanteric fixation nail (TFN). During the study period (March 2003-February
      2004) all patients with a trochanteric fracture Type A1-A3 (AO/ASIF
      classification) were eligible for the study, and 120 patients (mean age 81 years,
      range 47-100; male/female 1:4) subsequently enrolled. Most frequent was the
      (according to the AO classification) A.2.1. type of fracture (n=39) and the
      A.2.2. fracture (n= 39). Operation time from cut to stitch was 45 mins (minimal
      21/maximal 194). Thirty-seven (31%) postoperative X-rays were classified as very
      good, 60 (50%) as good, 18 (15%) as satisfying and five (4%) as bad post
      reposition results according to the Garden Alignment Index. The clinical results
      were documented by the time of hospital stay, postoperative mobilization and time
      of rehabilitation compared to the old social status. Time to hospital discharge
      was 17 days (9 /25). Overall complication rate was 7.5% (9 patients) with 5.8%
      [7] local wound infection; 1.6% [2] cutting out of the helical blade through the
      cortex of the femoral head. We had three (2.5%) hospital deaths in our patient
      group. We conclude that TFN is a safe and reliable technique. Compared with
      techniques like PFN and Gamma-nail, clinical results are excellent with less
      complications.

PMID- 16896747
TI  - The effect of locally applied vascular endothelial growth factor on meniscus
      healing: gross and histological findings.
AB  - INTRODUCTION: Tears in the peripheral part of the menisci have a better healing
      potential than tears in the central part, because the central two-thirds of the
      menisci are avascular. We hypothesized that healing of meniscus tears in the
      avascular zone can be promoted by the local application of the angiogenic factor
      vascular endothelial growth factor (VEGF). MATERIALS AND METHODS: A tear was
      created in the avascular zone of the medial meniscus in 18 merino sheep. The tear
      was then repaired with an uncoated suture (group 1), a suture coated with PDLLA
      (group 2), and by a suture coated with PDLLA/VEGF (group 3). RESULTS: After 6
      weeks, we observed increased immunostaining for factor VIII in the VEGF-treated
      group 3. However, in this treatment group no meniscus healed completely. In the
      uncoated suture group and in the PDLLA-coated-suture group, partial healing was
      observed in three animals and complete healing in three animals, respectively.
      CONCLUSION: In this experiment the local application of VEGF via PDLLA-coated
      sutures did not promote meniscus healing. Growth factors might not always be a
      promising tool for tissue repair.

PMID- 16896746
TI  - A particular solution in the treatment of primitive neoplasms of the distal third
      of the tibia. Presentation of a clinical case and review of the literature.
AB  - Primitive malignant neoplasms affecting the distal third of the tibia are
      altogether rare, and their treatment is considerably controversial. The authors
      describe the diagnostic procedure and a particular surgical strategy of limb
      salvage in a case of malignant fibrous histiocytoma located at the distal third
      of the tibia, in particular pointing out the difficulties in restoring the
      continuity of the skeletal tissues and of the muscle, and with a review of the
      relevant literature.

PMID- 16896748
TI  - Late presentation of congenital tracheo-oesophageal fistula.
AB  - Congenital tracheo-oesophageal fistula presenting in adulthood is extremely rare.
      Such a case is presented in a patient who suffered repeated chest problems as an
      infant, which persisted through the years, and was ultimately diagnosed as
      'bakers lung' due to his occupation. He was referred with persistent cough to the
      ENT department, and an upper endoscopy located a tracheo-oesophageal fistula,
      which was subsequently resected with complete resolution of his symptoms.
      Unresolving chest problems or persisting cough should alert the doctor to such a
      possible diagnosis.

PMID- 16896749
TI  - Concurrent primary Hodgkin's lymphoma and recurrent pleomorphic adenoma of the
      ipsilateral parotid gland: report of a rare case.
AB  - The synchronous occurrence of two histologically different and morphologically
      distinct tumours in a single parotid gland is an exceptionally rare and probably
      coincidental event. We have recently experienced such a case initially suspected
      of being a recurrent pleomorphic adenoma. Superficial parotidectomy, however,
      revealed two separate masses. Postoperative histopathological examination
      diagnosed the presence of a pleomorphic adenoma with a concurrent primary parotid
      gland Hodgkin's lymphoma arising from an intraglandular lymph node. The
      management of this case is presented along with a brief review of the literature
      concerning the evaluation and management of this rare entity.

PMID- 16896752
TI  - Follicular dendritic cell sarcoma of the tonsil: case report.
AB  - Follicular dendritic cell sarcomas are unusual, and extranodal origin is
      extremely rare. The English literature contains only eight cases in which this
      sarcoma has been presented as a tonsillar mass. We report a new case of
      follicular dendritic cell sarcoma of the tonsil in a 76 year old woman. The
      patient underwent diagnostic tonsillectomy for a left tonsillar mass, and
      follicular dendritic cell sarcoma was diagnosed based on histopathological and
      immunoperoxidase findings. Postoperative radiotherapy was performed. The patient
      is alive and disease-free at 4 years of follow-up. Without a high index of
      suspicion, this entity can easily be missed. We believe that follicular dendritic
      cell sarcoma should be included in the differential diagnosis for any tonsillar
      mass.

PMID- 16896750
TI  - External septal reconstruction with the use of polydioxanone foil: our
      experience.
AB  - We present our experience and results after using polydioxanone (PDS) foil in
      septal reconstruction. In a period of 2 years, 12 patients who were admitted in
      our department with severe septal deviation and breathing problems underwent
      septoplasty under general anaesthesia. The nasal septum was approached via an
      external approach. In all patients, after resecting and exposing the septum, the
      removable piece after being divided into straight pieces, was sutured onto an
      appropriate sized PDS foil and reimplanted together between the mucoperichondrium
      flaps. Sutures were placed to fixate the "new septum" to the nasal dorsum and to
      the anterior nasal spine. The immediate postoperative course was unremarkable and
      in a follow-up appointment 6 months and 1 year postoperatively, one complication
      occurred, with septum subluxation noted in one patient. Use of PDS foil in septal
      reconstruction is an important surgical option for the correction of the markedly
      deviated nasal septum. Fixation of the straightened and replanted septum at the
      nasal dorsal septum border with the upper lateral cartilages and at the nasal
      spine is essential.

PMID- 16896756
TI  - Voice quality improvement after management of unilateral vocal cord paralysis
      with different techniques.
AB  - The aim of this study was to objectively evaluate the voices of patients
      suffering from unilateral vocal cord paralysis, before and after endoscopic
      augmentation and thyroplasty. In the past, we used injectable Teflon to treat
      this condition; later techniques included collagen injection and Isshiki
      thyroplasty. In the last 7 years, preferred treatment methods have included
      Bioplastique injection and lipoaugmentation of the vocal cords as well as
      medialization thyroplasty using a titanium implant according to Friedrich. Pre-
      and postoperative data was evaluated and compared to 25 patients. Appropriate
      glottic closure of the vocal cords was achieved in every case, in most cases
      after the first intervention. We used voice range profile measurements to
      evaluate the results. An objective evaluation was performed using the Friedrich
      dysphonia index. Significant improvements were found: the dysphonia index
      decreased in every case, from an average of 2.47, preoperatively, to an average
      of 1.18 postoperatively. In agreement with earlier studies, voice pitch range was
      the only parameter that not significantly improved. There was no statistical
      difference between the lipoaugmentation and thyroplasty according to Friedrich.
      We concluded that both endoscopic methods and thyroplasty can be used to achieve
      an optimal result. Cases must be evaluated individually so that the best
      technique, or combination of methods can be determined.

PMID- 16896753
TI  - Multiple osteomas in the middle ear.
AB  - Osteomas in the middle ear are extremely rare and are generally solitary and
      small. We present a case of a 28-year-old female patient with multiple middle ear
      osteomas which arose from the promontory, epitympanum, and lateral semicircular
      canal. The osteomas were successfully removed by tympanomastoidectomy. This is
      the first reported case of a patient with middle ear osteomas arising from
      multiple sites.

PMID- 16896754
TI  - Acute sensorineural hearing loss immediately following a local anaesthetic dental
      procedure.
AB  - Acute sensorineural hearing loss is an uncommon phenomenon. We describe the first
      case of a 42-year-old lady who presented with acute sensorineural hearing loss
      occurring immediately after a dental procedure. Possible mechanisms are
      discussed. She was treated with high dose oral steroids, low molecular weight
      dextran and vasodilators with benefit.

PMID- 16896757
TI  - [Future developments in urology].

PMID- 16896751
TI  - Epithelial-myoepithelial carcinoma of the submandibular gland with symptomatic
      lung metastases treated with chemotherapy.
AB  - This report concerns a patient with symptomatic lung metastases from an
      epithelial-myoepithelial carcinoma of the submandibular gland. Although the
      efficacy of chemotherapy is unknown in this disease, our patient was treated with
      cisplatin combined with 5-fluorouracil and later with paclitaxel and
      cyclophosphamide. Chemotherapy allowed disease stabilization and relief of the
      pulmonary symptoms. This is the first report on the use of chemotherapy in this
      very rare salivary gland carcinoma.

PMID- 16896755
TI  - Otogenic skull base osteomyelitis caused by invasive fungal infection. Case
      report and literature review.
AB  - Otogenic skull base osteomyelitis (SBO) of fungal etiology is a very rare but
      life-threatening complication of inflammatory processes of the ear. The authors
      present a case of otogenic SBO caused by Aspergillus flavus in a 65-year-old man
      with a fatal course. Because of the encountered difficulties with the proper
      diagnosis and treatment, the authors reviewed the literature on the subject.

PMID- 16896760
TI  - [Thoughts on the future of urology from the professional policy viewpoint].

PMID- 16896762
TI  - [Bone formation in the ureter. Osseous metaplasia of an obstructed ureter].
AB  - Bone formation outside the skeleton is well known. Yet, ossification within the
      urogenital tract is rare. The case of a patient with distal ureteral obstruction,
      hydronephrosis, and subsequent circular osseous metaplasia of the ureter is
      presented. Open transperitoneal right-sided nephrectomy with partial resection of
      the ureter was performed. Intraoperatively and in histopathologic examination
      circular bone formation adjacent to the ureteral wall was detected. There was no
      evidence of malignancy. Early animal experiments in the twentieth century showed
      that bone metaplasia may be induced by epithelium of the urinary tract under
      certain conditions such as ischemia, inflammation, necrosis, sclerosis, and
      trauma. Osseous metaplasia may therefore be considered a differential diagnosis
      of calcification of the upper urinary tract in the absence of urolithiasis.

PMID- 16896758
TI  - [Darbepoetin alfa (Aranesp) as supportive therapy in patients with germ cell
      tumors].

PMID- 16896759
TI  - [Laparoscopic surgery in urology: Taining and education].
AB  - Relatively long learning curves and, therefore, initially longer operating times
      compared to conventional procedures are still a matter of debate. Today, there
      are numerous possibilities for learning laparoscopic techniques and establishing
      one's own laparoscopic programs, including various pelvitrainers and virtual
      reality computer programs. One useful and realistic way involves "wet lab"
      training programs for ablative and reconstructive procedures using the pig model.
      Today, laparoscopic urological surgery includes procedures with low (e.g.
      laparoscopy for undescended testicles), intermediate (laparoscopic pyeloplasty)
      and high level (laparoscopic/endoscopic prostatectomy) complexity. Therefore,
      laparoscopy should be an integral part of training in urology. A defined number
      of possibly multi-institutional training centers with well structured educational
      programs are needed. The main goal should be the standardization of surgical
      procedures as well as educational training programs in order to shorten
      individual learning curves and generate common quality standards.

PMID- 16896763
TI  - [A discussion of the differential diagnosis of the impaired erection].
AB  - In light of the fact that internationally accepted diagnostic criteria for
      erectile disorder are hardly considered in prevalence studies, the Berlin Male
      Study (BMS) was designed to collect data both on the frequency of dysfunctional
      erections experienced (DSM-IV criterion A) and the concomitance of related
      distress (DSM-IV criterion B). As a result, the age-adjusted total prevalence for
      erectile disorder (17.8%) was markedly lower than in other studies with
      comparable samples (40-79 years of age). Likewise, the age-dependent increase in
      prevalence was by far less prominent than commonly reported in the literature.
      These findings strongly suggest the necessity to clearly differentiate between
      erectile disorder, indicating that the patient is experiencing some degree of
      distress associated with his dysfunctional erection, and erectile dysfunction,
      indicating that the respective individual is not too concerned about his
      dysfunctional erection (with respect to erectile function, there is no reason to
      refer to the latter as a patient). The authors suggest that the internationally
      used abbreviation "ED" be differentiated into "EDy" when referring to erectile
      dysfunction and "EDi" when referring to erectile disorder. This extended
      perspective on differential diagnosis would not only make future studies (more)
      comparable, it would also do justice to clinical experience.

PMID- 16896761
TI  - [Standards and perspectives in diagnosis and therapy of bladder carcinoma].

PMID- 16896767
TI  - Bioavailability of slowly cycling soil phosphorus: major restructuring of soil P
      fractions over four decades in an aggrading forest.
AB  - Although low solubility and slow cycling control P circulation in a wide range of
      ecosystems, most studies that evaluate bioavailability of soil P use only indices
      of short-term supply. The objective here is to quantify changes in P fractions in
      an Ultisol during the growth of an old-field pine forest from 1957 to 2005,
      specifically changes with organic P (Po) and with inorganic P (Pi) associated
      with Fe and Al oxides as well as Ca compounds. Changes in soil P were estimated
      from archived mineral soil samples collected in 1962 shortly after pine seedlings
      were planted, and on six subsequent occasions (1968, 1977, 1982, 1990, 1997, and
      2005) from eight permanent plots and four mineral soil layers (0-7.5, 7.5-15, 15
      35, and 35-60 cm). Despite the net transfer of 82.5 kg ha(-1) of P from mineral
      soil into tree biomass and O horizons, labile soil P was not diminished, as
      indexed by anion exchange resins, and NaHCO(3) and Mehlich III extractants. An
      absence of depletion in most labile P fractions masks major restructuring of soil
      P chemistry driven by ecosystem development. During 28 years of forest growth,
      decreases were significant and substantial in slowly cycling Po and Pi associated
      with Fe and Al oxides and Ca compounds, and these accounted for most of the P
      supplied to biomass and O horizons, and for buffering labile soil fractions as
      well. Changes in soil P are attributed to the P sink strength of the aggrading
      forest (at 2.9 kg ha(-1) year(-1) over 28 years); legacies of fertilization,
      which enriched slowly cycling fractions of Po and Pi; and the changing
      biogeochemistry of the soil itself.

PMID- 16896766
TI  - Do female collared lizards change field use of maximal sprint speed capacity when
      gravid?
AB  - Locomotor ability is well-documented to decrease in gravid female lizards.
      However, no studies have examined what proportion of maximal sprint speed
      capacity gravid females use in nature or how a reduction in maximal capacity
      translates to changes in sprint speeds used in nature. Gravid females may
      compensate for reduced locomotor ability by increasing the proportion of their
      maximal capacity used in nature, or by changing their antipredator behaviour. I
      measured maximal sprint speed in the laboratory for female collared lizards
      (Crotaphytus collaris) while gravid and nongravid and then compared those to
      speeds used in the field while foraging and escaping predators, and also while
      gravid and nongravid. Females had significantly lower maximal sprint speed
      capacity while gravid, and they ran slower while foraging and escaping predators.
      However, gravid females did not increase the proportion of maximal capacity used
      in those contexts compared to when not gravid. Gravid females compensated for
      reduced locomotor capacity by staying closer to refugia but not by remaining more
      cryptic. These results suggest that the costs of reduced locomotor capacity may
      not be associated with direct costs while foraging or escaping predators, but
      instead with potential indirect effects associated with the change in
      antipredator behaviour.

PMID- 16896765
TI  - Assessing trophic interactions in a guild of primary parasitoids and facultative
      hyperparasitoids: stable isotope analysis.
AB  - Facultative hyperparasitism is likely to be the most common form of intraguild
      predation among parasitoids. However, difficulties associated with studying
      facultative hyperparasitoids in the field have hampered a thorough understanding
      of their trophic ecology. In this study, we used a combination of stable isotope
      analysis and published natural history information to infer trophic interactions
      in a guild of field-collected primary parasitoids and facultative
      hyperparasitoids that attack a gall-making midge on Baccharis pilularis. Our
      three a priori hypotheses were: (1) stable isotope values should increase
      incrementally from the host plant to higher trophic levels; (2) the two species
      of ectoparasitoids should exhibit higher stable isotope signatures than the two
      endoparasitoids, and; (3) the two facultative hyperparasitoids should exhibit
      stable isotope signatures that fall between zero and one trophic level steps
      above that observed for the primary parasitoids. Food webs inferred from stable
      isotope data generally agreed with previously published accounts of community
      structure. As expected, both delta(13)C and delta(15)N were progressively
      enriched in the heavy isotope from the host plant to the herbivorous midge to the
      parasitic wasps. Multivariate analysis of stable isotope data revealed that the
      two primary ectoparasitoids occupied a similar trophic niche, but were
      significantly different from the primary endoparasitoids. We attribute this
      result to "coincidental intraguild predation" by ectoparasitoids that develop on
      already-parasitized midge larvae. One of the facultative hyperparasitoids,
      Zatropis capitis, exhibited a stable isotope signature approximately one trophic
      step above the primary parasitoids. Unexpectedly, the second facultative
      hyperparasitoid, Mesopolobus sp., appeared to be developing as a primary
      parasitoid at all sites. Coupled with independent assessments of community
      structure, stable isotope analysis validated trophic links constructed by
      previous researchers and identified potential taxon-specific differences in
      trophic interactions for two facultative hyperparasitoids in the B. pilularis
      gall community.

PMID- 16896770
TI  - Population and clonal level responses of a perennial grass following fire in the
      northern Chihuahuan Desert.
AB  - Relationships involving fire and perennial grasses are controversial in
      Chihuahuan Desert grasslands of southern New Mexico, USA. Research suggests that
      fire delays the resprouting of perennial grasses well after two growing seasons.
      However, such results are confounded by livestock grazing, soil erosion, and
      drought. Additionally, post-fire grass responses may depend on initial clone
      size. We evaluated the effects of fire, grazing, and clone size on Bouteloua
      eriopoda (black grama) in southern New Mexico grasslands. Four 2-ha plots were
      established in each of four sites. Fire and grazing were applied or not applied
      in 1999 such that four treatment combinations were assigned randomly to plots
      within each site. Within each plot, small (0-10 cm(2) basal area), medium (10-30
      cm(2)), and large ( > 30 cm(2)) clones were initially mapped in five 0.91-m(2)
      quadrats where grass attributes and litter cover were evaluated before and at the
      end of two growing seasons following fire. Maximum fire temperature was also
      measured. At a population level, canopy and litter cover were each approximately
      50% less in burned than unburned areas. However, compared to initial levels,
      canopy height had increased by 10% at the end of the study, regardless of fire.
      At a clonal level, basal cover reductions were attributed mostly to large clones
      that survived fire. Smaller clone densities had decreased by as much as 19% in
      burned compared to unburned areas, and fire reduced the basal cover of medium
      clones. Basal and canopy cover, recruitment, and clone basal area decreased with
      increased fire temperatures. Almost all responses were independent of grazing,
      and interactive effects of grazing and fire were not detected. Fire did not kill
      all perennial grass clones, regardless of size. However, rapid responses were
      likely influenced by above-average precipitation after fire. Future studies in
      desert grasslands should examine how perennial grass dynamics are affected by
      fire, precipitation patterns, and interactions with grazing.

PMID- 16896768
TI  - Divergent nonlinear responses of the boreal forest field layer along an
      experimental gradient of deer densities.
AB  - The early responses of the field layer to changes in biotic and abiotic
      conditions are key determinants of the future composition and structure of
      forests where sustained heavy browsing pressure has depauperated the shrub
      understory. We investigated the relationships between white-tailed deer density
      and field layer plant community dynamics in boreal forests managed for wildlife
      and timber production. We hypothesized that the growth and reproduction of field
      layer plants are either: (H(1)) directly proportional to deer density, or (H(2))
      related to deer density through nonlinear relationships or (H(3)) through
      nonlinear relationships with thresholds. We tested these hypotheses using data
      from a controlled browsing experiment involving a gradient of deer densities (0,
      7.5, 15, 27 and 56 deer km(-2)) in interaction with timber harvesting conducted
      on Anticosti Island, Canada. In recent clearcuts, the dominant responses of the
      field layer plants were exponential recovery in growth and reproduction with
      decreasing deer densities. The abundance of browse-tolerant species such as
      grasses was positively related to deer density, suggesting an apparent
      competitive gain. These results support the prediction from our second
      hypothesis, although the presence of ecological thresholds should not be ruled
      out. Rapid changes in the early successional stages have potentially long-term
      consequences on successional patterns through processes such as the modulation of
      germination and early establishment success of seedlings from later successional
      species. Quantitative data as those presented here are essential for the
      development of ecosystem management prescriptions. On Anticosti Island, reduction
      of local deer densities to levels <15-7.5 deer km(-2) in the first 3 years
      following timber harvesting appears to be compatible with the regeneration
      dynamics of this system although lower levels of deer densities may be required
      for the conservation of browse-sensitive plant species.

PMID- 16896769
TI  - Indirect interactions between browsers and seed predators affect the seed bank
      dynamics of a chaparral shrub.
AB  - Interactions between herbivores and seed predators may have long-term
      consequences for plant populations that rely on persistent seed banks for
      recovery after unpredictable fires. We assessed the effects of browsing by deer
      and seed predation by rodents, ants and birds on the densities of seeds entering
      the seed bank of Ceanothus cuneatus var. rigidus, a maritime chaparral shrub in
      coastal California. Ceanothus produced many more seeds when protected from
      browsers in long-term experimental exclosures than did browsed plants, but the
      seed densities in the soil beneath browsed and unbrowsed Ceanothus were the same
      at the start of an intensive one-year study. The density of seeds in the soil
      initially increased in both treatments following summer seed drop: while
      densities returned to pre-drop levels within a few weeks under browsed plants,
      soil seed densities remained high for 5-8 months beneath unbrowsed plants. Rodent
      abundance (especially deer mice) was higher near unbrowsed plants than >30 m
      away, and rodents removed Ceanothus seeds from dishes in the experimental plots.
      At least in the short term, rodent density and rates of seed removal were
      inversely related to the intensity of browsing. Our data have management
      implications for maintaining viable Ceanothus populations by regulating the
      intensity of browsing and the timing, intensity and frequency of fires.

PMID- 16896772
TI  - Quantifying functional connectivity: experimental assessment of boundary
      permeability for the natterjack toad (Bufo calamita).
AB  - Like other pond-breeding amphibians, the natterjack toad (Bufo calamita)
      typically presents a patchy distribution. Because the species experiences high
      probabilities of local population extinction, its persistence within landscapes
      relies on both local and landscape-scale processes [dispersal allowing the
      (re)colonization of habitat patches]. However, the structure and composition of
      the matrix surrounding local populations can alter the dispersal rates between
      populations. As shown previously (Landscape Ecol 19:829-842, 2004), the locomotor
      performances of individuals at the dispersal stage depend on the nature of the
      component crossed: some landscape components offer high resistance to movement
      (high resistance or high viscosity components) whereas others allow high
      efficiency of movement (low resistance components). We now examine the ability of
      individuals to discriminate between landscape components and select low
      resistance components. Our experimental study investigates the ways in which
      young natterjack toads choose from among landscape components common to southern
      Belgium. Toadlets (the dispersal stage) were experimentally confronted with
      boundaries between surrogates of sandy soils, roads, forests, agricultural fields
      and intensive pastures. Our results show: 1 the ability of toadlets to react to
      boundaries between landscape components, 2 differences in permeability among
      boundaries, and 3 our inability to predict correctly the permeability of the
      boundaries from the patch-specific resistance assessed previously. Toadlets
      showed a preference for bare environments and forests, whereas they avoided the
      use of agricultural environments. This pattern could not be explained in terms of
      patch-specific resistance only, and is discussed in terms of mortality risks and
      resource availability in the various landscape components, with particular
      attention to repercussions on conservation strategies.

PMID- 16896771
TI  - Aboveground and belowground responses to quality and heterogeneity of organic
      inputs to the boreal forest.
AB  - Leaf litter and other organic resources returned to the soil are important
      regulators of ecological processes in forest ecosystems, and their ecological
      impacts may be strongly influenced both by their quality and by interactions
      between coexisting resource types. To date, most studies on effects of resource
      identity and mixing have only involved leaf litter, despite the fact that other
      resource types constitute a major input to the soil. We investigated how quality
      and heterogeneity of organic substrates found in boreal forests affects the
      activity and community structure of soil microbes, and plant growth. Six organic
      substrates (wood, charcoal, berries, sporocarps, vertebrate faeces and leaf
      litter) were added singly or in mixtures of two, three and six resource types to
      pots containing forest soil (with or without tree seedlings of Betula pendula
      Roth). The largest positive effects of single substrates on microbial basal
      respiration (BR), substrate-induced respiration (SIR) and microbial metabolic
      quotient (qCO(2)) were found for nutrient-rich substrates (faeces and sporocarps)
      or substrates with high sugar-content (berries). Mixing of substrates had no
      effect on BR or SIR, but decreased qCO(2) or altered the microbial community
      structure for specific combinations of substrates. In contrast to the niche
      complementarity hypothesis, microbial catabolic diversity was not stimulated by
      greater diversity of resources. Seedling growth responses to single substrates
      were neutral or negative; the inhibition of growth probably resulted largely from
      microbial competition for nutrients. Substrate mixing enhanced seedling nutrient
      uptake and growth for all mixtures containing sporocarps and leaf litter.
      Overall, plants responded more strongly to resource heterogeneity than microbes,
      and synergistic effects only occurred when nutrient-rich substrates were present
      within the substrate mixtures. In particular, our results demonstrate a role for
      complex and non-additive interactions among previously overlooked resource types
      returned to the soil in influencing ecosystem functions such as nutrient cycling
      and plant productivity.

PMID- 16896775
TI  - Immigration and zooplankton community responses to nutrient enrichment: a
      mesocosm experiment.
AB  - Dispersal can be an important determinant of local diversity and species
      composition, but evidence for effects of the regional species pool on local
      zooplankton communities has been mixed. Theory and experiments suggest that
      immigration will be necessary for maintenance of community diversity and
      functioning during periods of environmental change; conversely, fluctuating
      resource levels may increase the likelihood of invasion success. We conducted a
      factorial-design mesocosm experiment to test the effects of a nutrient pulse and
      weekly immigration from other lakes on the diversity and composition of a pelagic
      zooplankton community. Contrary to expectations, there were no interactive
      effects of nutrient enrichment and immigration on any measure of diversity, and
      the initial shift in community composition in response to the nutrient pulse did
      not depend on the introduction of new species or genotypes from more productive
      lakes. Although immigration increased species richness in enclosures, success of
      most colonising species was poor. However, the dispersal treatment appears to
      have enabled a stronger predator response to increased herbivore numbers in
      nutrient-pulsed enclosures, leading to an eventual decline in the abundance of
      some herbivorous species in response to immigration. We conclude that community
      invasibility was not influenced by productivity, and that dispersal limitation
      did not strongly constrain the response of the zooplankton community to our
      applied disturbance. This indicates an unexpected resistance to change in species
      composition and diversity in spite of disturbance, and suggests that, in our
      study system, changes in the abundance of resident species are more important
      than introductions of new species in the community response to short-term
      environmental change.

PMID- 16896774
TI  - A field test of the directed deterrence hypothesis in two species of wild chili.
AB  - The directed deterrence hypothesis posits that secondary metabolites in ripe
      fruit function to deter fruit consumption by vertebrates that do not disperse
      seeds, while not impacting consumption by those that do. We tested this
      hypothesis in two species of wild chilies (Capsicum spp.). Both produce fruits
      that contain capsaicinoids, the compounds responsible for the pungency of
      chilies. Previous work suggests seed-dispersing birds but not seed-destroying
      rodents consume chili fruits, presumably because rodents are deterred by
      capsaicin. However, fruit removal from chili plants by rodents and other mammals
      has not been previously explored. Because laboratory rodents can develop a
      preference for capsaicin, it is quite possible that wild rodents are natural
      consumers of chili fruits. We monitored the fate of 125 marked fruits of Capsicum
      chacoense and 291 fruits of Capsicum annuum. For both species, essentially all
      fruit removal occurred during the day, when rodents are inactive. Video
      monitoring revealed fruit removal only by birds, mostly by species known to
      disperse chili seeds in viable condition. Furthermore, these species are from
      taxonomic groups that tend to specialize on lipid-rich fruits. Both species of
      chili produce fruits that are unusually high in lipids (35% in C. chacoense, 24%
      in C. annuum). These results support the directed deterrence hypothesis and
      suggest that fruiting plants distinguish between seed predators and seed
      dispersers by producing fruits that repel the former and attract the latter.

PMID- 16896764
TI  - A decision model to compare health care costs of olanzapine and risperidone
      treatment for schizophrenia in Germany.
AB  - Second-generation atypical antipsychotics such as clozapine, olanzapine,
      risperidone, quetiapine, ziprasidone, amisulpride and ariprazole offer the
      potential to reduce the significant health care resource demands in the treatment
      of schizophrenia through improved levels of initial clinical response and reduced
      levels of long-term acute relapse. However, the optimal sequencing of these drugs
      remains unclear. To consider this issue from a health economic viewpoint a
      decision model approach was used comparing healthcare costs and clinical outcomes
      when treating patients with alternative sequences of atypical antipsychotic
      treatment. Treated patients were assumed to be in a current acute episode with at
      least a 10-year history of disease and to be naive to previous atypical
      treatments. Treatment strategies were based on either first-line olanzapine or
      risperidone with switching to the alternative drug as second-line treatment
      following an inadequate clinical response to first-line drug therapy. Clinical
      response data were derived from a pivotal published comparative study of both
      olanzapine and risperidone. Published data on the long-term use of antipsychotic
      drugs where used wherever possible to populate the model for relapse rates during
      the maintenance phase. Health care resource data were defined for Germany based
      on expert clinical opinion. A treatment strategy of first-line olanzapine was
      shown to be cost saving over a 1-year period, with additional clinical benefits
      in the form of avoided relapses. The model suggests that over the first year of
      treatment a strategy of first-line olanzapine is associated with lower risk of
      additional relapse (0.33 fewer acute relapses per 100 patients per year) and with
      cost savings (euro 35,306 per 100 patients per year). There is a need for longer
      term direct in-trial comparisons of atypical antipsychotics to confirm these
      indicative results.

PMID- 16896773
TI  - Is abundance a species attribute? An example with haematophagous ectoparasites.
AB  - Population density is a fundamental property of a species and yet it varies among
      populations of the same species. The variation comes from the interplay between
      intrinsic features of a species that tend to produce repeatable density values
      across all populations of the same species and extrinsic environmental factors
      that differ among localities and thus tend to produce spatial variation in
      density. Is inter-population variation in density too large for density to be
      considered a true species character? We addressed this question using data on
      abundance (number of parasites per individual host, i.e. equivalent to density)
      of fleas ectoparasitic on small mammals. The data included samples of 548 flea
      populations, representing 145 flea species and obtained from 48 different
      geographical regions. Abundances of the same flea species on the same host
      species, but in different regions, were more similar to each other than expected
      by chance, and varied significantly among flea species, with 46% of the variation
      among samples accounted by differences between flea species. Thus, estimates of
      abundance are repeatable within the same flea species. The same repeatability was
      also observed, but to a lesser extent, across flea genera, tribes and
      subfamilies. Independently of the identity of the flea species, abundance values
      recorded on the same host species, or in the same geographical region, also
      showed significant statistical repeatability, though not nearly as strong as that
      associated with abundance values from the same flea species. There were also no
      strong indications that regional differences in abiotic variables were an
      important determinant of variation in abundance of a given flea species on a
      given host species. Abundance thus appears to be a true species trait in fleas,
      although it varies somewhat within bounds set by species-specific life history
      traits.

PMID- 16896776
TI  - Age-dependent shift in response to food element composition in Collembola:
      contrasting effects of dietary nitrogen.
AB  - We examined the effect of different food qualities, in terms of the C:N:P
      content, on the collembolan Hypogastrura viatica. We hypothesised that (faster
      growing) juveniles would have higher demands for P and N than adults; this,
      however, was rejected by our experiments. There was no difference between the
      elemental compositions of juveniles and adults. In food preference experiments,
      juveniles and adults were offered green algae Raphidocelis subcapitata with three
      different C:N:P ratios. There was a strong shift in dietary response with age;
      juveniles preferred algae with low or medium N contents over the most N-rich
      algae, whereas adults showed the opposite. No response was seen when the specific
      P content in the food was varied. Juveniles fed on algae with high N content
      showed lower growth rates and survival than those fed on algae with other food
      qualities. In contrast, adults had lowest growth rates when fed on algae with a
      low N content. The negative effect on juveniles of the most N-rich diet appeared
      to be a toxic response that was directly or indirectly related to the algal N
      content. Adults had higher tolerance for N-rich diets, but were also more likely
      to face dietary N-limitation. These animals face a stoichiometric trade-off
      scenario in the sense that adaptation to maximise retention of a limiting element
      may result in reduced physiological ability to cope with excessive elements when
      feeding on "richer" diets, and vice versa. This problem is partly solved in H.
      viatica by contrasting selective feeding and ontogenetic dietary shifts between
      juveniles and adults.

PMID- 16896777
TI  - Speckled eggs: water-loss and incubation behaviour in the great tit Parus major.
AB  - Many small passerine birds worldwide lay white eggs speckled with red, brown and
      black protoporphyrin pigment spots (maculation). Unlike some patterns of avian
      eggshell pigmentation which clearly serve a crypsis or signalling function, the
      ubiquity of maculation among passerines suggests that its origins lie in another
      function, not specific to any particular ecological or behavioural group.
      Elsewhere, we have presented evidence that protoporphyrin pigments serve a
      structural function related to eggshell thickness and calcium availability:
      eggshell maculation in the great tit Parus major increases with decreasing soil
      calcium levels, pigments demarcate thinner areas of shell, and both the pigment
      intensity and distribution are related to shell thickness. Here we show that
      maculation also affects the rate of water loss from the egg during incubation
      (approximately Mass Loss per Day or MLD, which is critical to egg viability), but
      not that of unincubated eggs. We also demonstrate, both by observation and
      experiment, that the effect of female incubation behaviour on MLD compensates in
      some way for variation in egg characteristics, and that differences between
      females in the degree of such compensation are related to differences in clutch
      maculation. Our results suggest that, while a principal function of maculation in
      this species may be to strengthen the eggshell, it may also reduce eggshell
      permeability when large amounts of pigment are used, and that this necessitates a
      behavioural adjustment from the female during incubation. We discuss these
      findings and make further testable predictions from our model.

PMID- 16896778
TI  - Nonadditive effects of flower damage and hummingbird pollination on the fecundity
      of Mimulus luteus.
AB  - Flower herbivory and pollination have been described as interactive processes
      that influence each other in their effects on plant reproductive success. Few
      studies, however, have so far examined their joint effects in natural
      populations. In this paper we evaluate the influence of flower damage and
      pollination by the hummingbird Oreotrochilus leucopleurus on the fecundity of the
      Andean monkey flower Mimulus luteus. We performed a 2x2 factorial experiment,
      with artificial clipping of lower petals and selective exclusion of the
      hummingbird as main factors. In spite of the relatively low proportion (27.5%) of
      the variance in seed production accounted for by the full factorial model,
      artificial damage and hummingbird exclusion, as well as their interaction, were
      highly significant, indicating nonadditive effects of factors on plant fecundity.
      In the presence of hummingbirds, undamaged flowers had a seed production that was
      1.7-fold higher than for damaged flowers, suggesting that the effect of flower
      damage on female reproductive success occurs probably as a consequence of
      hummingbird discrimination against damaged corollas. This result indicates that
      the impact of flower herbivory on plant fecundity was contingent on the presence
      or absence of hummingbirds, suggesting that pollinators may indirectly select for
      undamaged and probably resistant flower phenotypes. A second interaction effect
      revealed that undamaged flowers produced 78.5% more seeds in the absence of
      rather than in the presence of O. leucopleurus, raising the question of the
      ecological mechanism involved. We suggest that the strong territorial behavior
      exhibited by the bee Centris nigerrima may confine the foraging activities of the
      remaining bee species to safe sites within exclosures. Overall, our results
      provide evidence that hummingbird pollination and flower herbivory have
      interdependent effects on M. luteus fecundity, which indicates that it will be
      difficult to predict their ecological and evolutionary consequences unless
      interactions are analyzed in an integrated form.

PMID- 16896779
TI  - Habitat structure, trophic structure and ecosystem function: interactive effects
      in a bromeliad-insect community.
AB  - Although previous studies have shown that ecosystem functions are affected by
      either trophic structure or habitat structure, there has been little
      consideration of their combined effects. Such interactions may be particularly
      important in systems where habitat and trophic structure covary. I use the
      aquatic insects in bromeliads to examine the combined effects of trophic
      structure and habitat structure on a key ecosystem function: detrital processing.
      In Costa Rican bromeliads, trophic structure naturally covaries with both habitat
      complexity and habitat size, precluding any observational analysis of
      interactions between factors. I therefore designed mesocosms that allowed each
      factor to be manipulated separately. Increases in mesocosm complexity reduced
      predator (damselfly larva) efficiency, resulting in high detritivore abundances,
      indirectly increasing detrital processing rates. However, increased complexity
      also directly reduced the per capita foraging efficiency of the detritivores.
      Over short time periods, these trends effectively cancelled each other out in
      terms of detrital processing. Over longer time periods, more complex patterns
      emerged. Increases in mesocosm size also reduced both predator efficiency and
      detritivore efficiency, leading to no net effect on detrital processing. In many
      systems, ecosystem functions may be impacted by strong interactions between
      trophic structure and habitat structure, cautioning against examining either
      effect in isolation.

PMID- 16896780
TI  - Mechanisms of recovery and resilience of different components of mosaics of
      habitats on shallow rocky reefs.
AB  - Understanding the mechanisms producing and maintaining discontinuities between
      patches in mosaics of habitats is necessary to predict changes in patterns of
      abundance and distribution of species. On temperate rocky reefs, physical and
      biological disturbance can result in a mosaic of patches of encrusting coralline,
      turf- or canopy-forming algae. We experimentally investigated the effects of
      disturbance within and at the boundary between these patches, in order to
      identify mechanisms accounting for re-colonisation of space and to assess whether
      the response of boundaries can alter the relative size of contrasting habitats.
      Also, we tested whether the resilience of the different types of assemblages
      depends on species richness (i.e. number of taxa present) of habitats or,
      alternatively, on other properties of systems like differences in life-history
      traits of dominating species. Although the nature of the mechanisms generating
      differences among habitats changed among different stages of the colonisation,
      local processes (within patches) prevailed over larger scale processes (among
      patches) in determining early patterns of colonisation of space in mosaics. By
      the end of the experiment, assemblages in clearings at boundaries had recovered
      to the undisturbed reference condition, in contrast to clearings within barren
      patches or algal turfs. Boundaries represent, therefore, relatively more stable
      components of the mosaic, with greater resilience than adjacent habitats.
      Although sea urchins are often indicated as the main force regulating the
      proportion of contrasting habitats on shallow rocky reefs, determining the nature
      of variation in the interaction between species dominating each type of habitat
      is crucial to understand dynamics of mosaics. Finally, our study provides
      evidence that resilience could not be entirely controlled by initial species
      diversity, suggesting that different proportions of dominant taxa could influence
      the stability of natural systems.

PMID- 16896781
TI  - Effects of food abundance, density and climate change on reproduction in the
      sparrowhawk Accipiter nisus.
AB  - The reproductive success of predators depends on abiotic environmental
      conditions, food abundance and population density, and food abundance, density
      and their interactions may respond to changes in climatic conditions. Timing of
      reproduction by five of the eight numerically most common prey of the sparrowhawk
      Accipiter nisus advanced significantly since 1971, during a period of temperature
      increase. There was no evidence that mean laying date or any other reproductive
      parameter of sparrowhawks changed consistently during the study period 1977-1997.
      Laying date advanced and percentage of unsuccessful female sparrowhawks decreased
      with beech mast in the current year, an index of food abundance for avian prey.
      Mean laying date of sparrowhawks was advanced in warmer springs, and although
      mean clutch size was not larger in warm than in cold springs, mean brood size of
      successful pairs and breeding success increased in such springs, showing that
      sparrowhawks enjoyed a fitness gain when reproducing early. The timing of
      sparrowhawk reproduction with respect to the peak in abundance of fledgling prey
      increased, from a good match between mean timing of fledging by prey and maximum
      demand for food by the predator in 1977, to reproduction occurring later than the
      peak in fledging prey availability in 1997. The size of the breeding population
      of sparrowhawks was not predicted by mean spring temperature, the size of the
      breeding population the previous year or beech mast crop. The size of the post
      breeding population was predicted by size of the breeding and post-breeding
      population the previous year and by the proportion of unsuccessful females the
      current year. These findings imply that sparrowhawks did not respond to change in
      climate, although climate changed the timing of reproduction by the main prey
      species.

PMID- 16896782
TI  - Data mining in pharmacovigilance: lessons from phantom ships.

PMID- 16896783
TI  - Predicting brain concentrations of drug using positron emission tomography and
      venous input: modeling of arterial-venous concentration differences.
AB  - OBJECTIVE: In a positron emission tomography (PET) study, the concentrations of
      the labeled drug (radiotracer) are often different in arterial and venous plasma,
      especially immediately following administration. In a PET study, the transfer of
      the drug from plasma to brain is usually described using arterial plasma
      concentrations, whereas venous sampling is standard in clinical pharmacokinetic
      studies of new drug candidates. The purpose of the study was to demonstrate the
      modeling of brain drug kinetics based on PET data in combination with venous
      blood sampling and an arterio-venous transform (T(av)). METHODS: Brain kinetics
      (C(br)) was described as the convolution of arterial plasma kinetics (C(ar)) with
      an arterial-to-brain impulse response function (T(br)). The arterial plasma
      kinetics was obtained as venous plasma kinetics (C(ve)) convolved with the
      inverse of the arterio-venous transform (T(av) (-1)). The brain kinetics was then
      given by C(br)=C(ve)*T(av) (-1)*T(br). This concept was applied on data from a
      clinical PET study in which both arterial and venous plasma sampling was done in
      parallel to PET measurement of brain drug kinetics. The predictions of the brain
      kinetics based on an arterial input were compared with predictions using a venous
      input with and without an arterio-venous transform. RESULTS: The venous based
      models for brain distribution, including a biexponential arterio-venous
      transform, performed comparably to models based on arterial data and better than
      venous based models without the transform. It was also shown that three different
      brain regions with different shaped concentration curves could be modeled with a
      common arterio-venous transform together with an individual brain distribution
      model. CONCLUSION: We demonstrated the feasibility of modeling brain drug
      kinetics based on PET data in combination with venous blood sampling and an
      arterio-venous transform. Such a model can in turn be used for the calculation of
      brain kinetics resulting from an arbitrary administration mode by applying this
      model on venous plasma pharmacokinetics. This would be an important advantage in
      the development of drugs acting in the brain, and in other circumstances when the
      effect is likely to be closer related to the brain than the plasma concentration.

PMID- 16896784
TI  - Prevalence and patterns of antidepressant drug use during pregnancy.
AB  - OBJECTIVE: The aim of this study was to determine the extent and patterns of
      antidepressant use before, during and after pregnancy in a large population in
      The Netherlands. METHODS: Health care records and prescription data from one of
      the largest Dutch health insurance companies were analysed. The study cohort
      consisted of 29,005 women who had live births in the period between January 2000
      and July 2003. Antidepressant drug use during a specified period was defined as
      there being a record of a prescription during that period. RESULTS: During the
      first trimester of pregnancy 2% of all pregnant women of the study cohort were
      found to have taken antidepressants; in the second and third trimesters, this
      figure had dropped to 1.8% of all pregnancies. Antidepressant use before as well
      as during pregnancy was almost twofold higher in women over 35 years of age than
      in those under 35 years. Almost 60% of the women who used antidepressants before
      pregnancy stopped taking them in the first trimester, and a smaller number
      stopped thereafter. Of all women using antidepressants during pregnancy, one
      third started this medication during gestation. In the 3 months following
      delivery, the prevalence of antidepressant use was the same as before pregnancy
      (2.9%). There was no shift to benzodiazepines in the group of women who stopped
      taking antidepressants during pregnancy. Although paroxetine and fluoxetine were
      the most frequently used antidepressants among the study group, all modern
      antidepressants were used. CONCLUSION: A considerable number of women are being
      exposed to antidepressants throughout pregnancy up until delivery. One
      consequence of this is that their newborns need special care and supervision
      during the first days of life. However, women who stop taking the medication may
      risk a relapse of their illness, and this may also have a negative effect on the
      child.

PMID- 16896786
TI  - Conventional and sustained-release valproate in children with newly diagnosed
      epilepsy: a randomized and crossover study comparing clinical effects, patient
      preference and pharmacokinetics.
AB  - OBJECTIVE: It has been suggested that sustained-release valproate (VPA)
      formulations may be more effective and better tolerated than conventional VPA due
      to better compliance and lower fluctuations in VPA serum concentrations, but
      comparative trials with conventional VPA in children are scarce. This randomized
      and crossover trial compared the efficacy (complete control of seizures), the
      tolerability, and the patient (or parents) preference of conventional VPA twice
      daily (CVbid) with those of sustained-release chrono VPA twice daily (ChVbid),
      once daily in the morning (ChVom) or once daily in the evening (ChVoe) in
      monotherapy. METHODS: The study was carried out in 48 children (29 girls), aged 5
      14 years, with newly diagnosed partial epilepsy (n=26), or idiopathic generalized
      epilepsy (n=22). The study duration was 16 months (four phases of 4 months each).
      VPA pharmacokinetics data were also compared in the different regimens. Mean VPA
      dosage was of approximately 870 mg/day (approximately 22 mg/kg/day) and mean VPA
      concentration was of approximately 89 mg/l at 12 h post-dose and of 54 mg/l at 24
      h post-dose. RESULTS: By intention in treatment there were no significant
      differences in efficacy (73%, 83%, 77% and 75%, respectively) or in adverse
      reaction frequency (56%, 58%, 67% and 46%, respectively). There were significant
      differences, however, in patient (or parents) preference, the order being ChVoe
      (31%) > ChVom (25%) > CVbid (17%) > ChVbid (8%). The mean VPA serum concentration
      fluctuation between 4 h and 0 h post-morning-dose was nonsignificantly lower
      after CVbid than after ChVbid. Fluctuation was significantly higher after ChVom
      than after CVbid or ChVbid. The mean VPA serum concentration difference between
      12 h and 24 h post-dose was approximately 40 mg/l. CONCLUSION: Although our
      results should be confirmed by a larger study, they suggest that the efficacy and
      tolerability of chrono valproate is similar to that of conventional valproate,
      and that the main advantage is the once-daily administration.

PMID- 16896785
TI  - Effects of amlodipine-atorvastatin combination on inflammation markers and
      insulin sensitivity in normocholesterolemic obese hypertensive patients.
AB  - OBJECTIVE: The objective of this study was to assess the effect of amlodipine
      atorvastatin combination on plasma interleukin-6 (IL-6), tumor necrosis factor
      alpha (TNF-alpha) and insulin sensitivity in normocholesterolemic obese
      hypertensive patients. MATERIALS AND METHODS: After a 4-week placebo wash-out
      period, 50 normocholesterolemic [total cholesterol (TC) <5.2 mmol/L], obese (BMI
      >/=30 kg/m(2)) hypertensive patients (DBP >90 and <105 mm Hg and SBP >140 and
      <180 mm Hg) were randomly treated with amlodipine (10 mg) or with amlodipine (10
      mg) plus atorvastatin (20 mg) according to a cross-over design; each treatment
      had a 12-week duration. At the end of the placebo and of each treatment period,
      blood pressure (BP), TNF-alpha, IL-6, insulin resistance (IR) by homeostasis
      model assessment of IR index (HOMA-IR) and TC were evaluated. RESULTS: Amlodipine
      monotherapy decreased both SBP (-17.1 mm Hg, p=0.008 vs. placebo) and DBP (-14.3
      mm Hg, p=0.008) as well as TNF-alpha (from 3.66+/-1.6 to 3.09+/-1.1 pg/ml,
      p=0.045) and HOMA-IR (from 4.58+/-0.7 to 3.88+/-0.6, p=0.007). The amlodipine
      atorvastatin combination produced a decrease in SBP (-22.5 mm Hg, p=0.0007 vs.
      placebo, p=0.039 vs. amlodipine), DBP (-17.7 mm Hg, p=0.0007 vs. placebo; p=0.04
      vs. amlodipine), TNF-alpha (2.59+/-0.9 pg/mL, p=0.007 vs. placebo and p=0.038 vs.
      amlodipine) and HOMA-IR (2.86+/-0.4, p=0.0008 vs. placebo and p=0.007 vs.
      amlodipine). The combination reduced IL-6 (from 7.93+/-1.9 to 5.59+/-1.2 pg/mL,
      p=0.008 vs. placebo and p=0.007 vs. amlodipine) and TC (from 4.3+/-0.5 to 3.6+/
      0.4 mmol/L, p=0.008 vs. placebo and vs. amlodipine). HOMA-IR changes
      significantly correlated with TNF-alpha changes (r=0.38, p<0.05) during
      combination but not during amlodipine monotherapy. In normocholesterolemic, obese
      hypertensive patients, the amlodipine-atorvastatin combination decreased
      inflammatory markers and IR more than amlodipine monotherapy and produced a
      greater SBP and DBP reduction.

PMID- 16896787
TI  - Prospective sonographic evaluation of fentanyl side effects on the neonatal
      gallbladder.
AB  - OBJECTIVE: In an effort to minimise the stress and pain of mechanically
      ventilated neonates, the application of opioids has increased markedly. Abdominal
      adverse effects of opioid analgesics are constipation and increased pressure in
      the biliary system. Our aim was to evaluate the impact of continuous intravenous
      infusion of fentanyl on the volume of the neonatal gallbladder and to assess
      potential gastrointestinal side effects. METHODS: We prospectively matched pairs
      of 40 mechanically ventilated neonates (28-42 gestational weeks) under total
      parenteral nutrition and midazolam sedation. One group (20 patients) received
      continuous fentanyl infusions (dose 0.5-2 microg kg(-1) h(-1)) the other group
      (20 patients) served as controls. Sonographic measurements of gallbladder length,
      depth and width were performed to calculate gallbladder volume using the
      ellipsoid method. Repeated ultrasound images, date of meconium release and serum
      bilirubin levels were documented. RESULTS: Fentanyl application was not
      associated with gallbladder sludge/stones, gallbladder hydrops,
      hyperbilirubinemia or prolonged meconium release. Neonatal gallbladder length,
      width and volume did not differ significantly (data expressed as mean, standard
      deviation, median, interquartile range: length (cm) 3.16+/-0.68, 3.3, 0.675 vs
      3.06+/-0.62, 3.3, 1.1; P=0.645; width (cm) 1.02+/-0.23, 1.0, 0.28 vs 0.89+/-0.27,
      0.9, 0.38, P=0.12; volume (cm(3)) 1.52+/-0.67, 1.7, 0.86 vs 1.22+/-0.77, 1.09,
      1.19, P=0.20). CONCLUSION: In our study fentanyl caused no major complications in
      the biliary system and intestine of ventilated preterm and term neonates.
      Sonographic investigations of the gallbladder under fentanyl treatment may be
      dispensable. Further investigations are required to assess adverse
      gastrointestinal effects.

PMID- 16896788
TI  - Detection of potential drug interactions - a model for a national pharmacy
      register.
AB  - OBJECTIVE: The widespread use of pharmaceuticals prescribed by different
      physicians has caused the Swedish government to propose a new legislation with
      registration of all prescriptions dispensed at the Swedish pharmacies. In the
      present study, we wanted to examine the frequency, distribution and determinants
      of potential drug interactions. METHODS: The prescriptions from all individuals
      (n=8,214) with two or more prescriptions during October 2003 to December 2004
      were collected from the ongoing Jamtland cohort study of a total of about 11,000
      individuals. Potential drug-drug interactions were detected with a computerized
      interaction detection system and classified according to clinical relevance
      (types A-D). RESULTS: On average each individual filled 14.6 (men 14.3, women
      14.8) prescriptions during the study period. 3.6% of the individuals used more
      than 15 different drugs. The number of detected potential drug interactions type
      A-D was 4,941 (men 1,949, women 2,992). The risk of receiving a potential
      interaction type A-D was estimated as the cumulative incidence 0.26 (2,116/8,214)
      overall, 0.22 (748/3,467) for men and 0.29 (1,368/4,747) for women during the 15
      month study period. The age adjusted risk, RR(adj), for women was estimated as
      1.30. Excluding sex hormones and modulators of the genital system, the RR(adj)
      was 0.96, with no elevated risk for women. For potential interactions type D,
      that might have serious clinical consequences, 167 (cumulative incidence 0.0203)
      individuals (72 men, cumulative incidence 0.0208, 95 women cumulative incidence
      0.0200) were detected. The risk of receiving a combination of potentially
      interacting drugs was positively correlated to age and polypharmacy. The
      cumulative incidence for elderly was estimated as 0.36 (65-84 years) and 0.39 (85
      years and above). The relative risk for individuals with 15 drugs or more was
      estimated as 3.67 (95% CI 3.46-3.90). CONCLUSION: In a general population there
      were relatively few severe potential drug interactions. The new Swedish national
      pharmacy register will provide health care professionals with a powerful tool to
      systematically review all prescriptions. An alert system should focus on the more
      potential drug interactions, type C-D, with close monitoring of elderly and
      patients with polypharmacy.

PMID- 16896789
TI  - Brassica napus Rop GTPases and their expression in microspore cultures.
AB  - Androgenesis in plants involves a shift in development that causes cultured
      microspore cells to form embryos rather than continue to develop pollen. In
      Brassica napus microspore culture a mild heat stress is used to switch on embryo
      development. An early hallmark of embryogenesis in this system is a symmetrical
      division of the nucleus instead of the asymmetric division that occurs during
      pollen formation. ROP GTPases act as molecular switches in a variety of
      developmental processes; therefore, the current study was initiated to examine
      whether they might be involved in androgenesis. Five distinct Rop genes with
      nucleic acid similarities ranging from 82 to 93% to Arabidopsis Rop1 were
      isolated from B. napus cv Topas. A Southern blot hybridization with a BnRop
      sequence probe suggested that there are 11-15 ROP gene family members in B.
      napus. RT-PCR reactions with PCR primers specific to BnRop5, BnRop6, BnRop9 and
      BnRop10 showed that expression of the BnRop5 was restricted to pollen but the
      others were detected in leaf, root, stem and pollen tissue. Pollen-like cells
      obtained from 3-day-old cultures by flow cytometric sorting had BnRop5 transcript
      levels that were 2.8 times higher than in flow sorted embryogenic microspores.
      Conversely, the BnRop9 transcript levels were 2.5-fold higher in the embryogenic
      cells than in the pollen-like cells. The potential involvement of specific ROPs
      in early stage microspore culture responses is discussed.

PMID- 16896790
TI  - Changes in photoreceptor currents and their sensitivity to the chemoeffector
      tryptone during gamete mating in Chlamydomonas reinhardtii.
AB  - Chlamydomonas reinhardtii Dangeard generates photoreceptor currents (PCs) upon
      light excitation. These currents play a key role in the signal transduction chain
      for photomotility responses. We have previously found that inhibition of PCs by
      tryptone occurs only in gametes that display chemotaxis toward this agent, and is
      not observed in chemotactically insensitive vegetative cells. Here we show that
      the sensitivity to tryptone is characteristic of gametes of both mating types,
      and examine the influence of gamete mating on PCs and their sensitivity to
      tryptone. The amplitude of PCs increases after cell fusion, but the sensitivity
      of these currents to tryptone decreases upon flagellar adhesion and/or an
      increase in the intracellular cAMP concentration. Net chemotaxis toward tryptone
      is reduced in young zygotes compared to gametes. We conclude that gamete mating
      leads to rapid inactivation of a gamete-specific chemosensory system.

PMID- 16896791
TI  - The roles of specific xanthophylls in light utilization.
AB  - To evaluate the role of specific xanthophylls in light utilization, wild-type and
      xanthophyll mutant plants (npq1, npq2, lut2, lut2npq1 and lut2npq2) from
      Arabidopsis thaliana were grown under three different light regimes: 30 (low
      light, LL), 150 (medium light, ML) and 450 (high light, HL) mumol photons m(-2)
      s(-1). We studied the pigment content, growth rate, xanthophyll cycle activity,
      chlorophyll fluorescence parameters and the response to photoinhibition. All
      genotypes differed strongly in the growth rates and the resistance against
      photoinhibition. In particular, replacement of lutein (Lut) by violaxanthin (Vx)
      in the lut2npq1 mutant did not affect the growth at non-saturating light
      intensities (LL and ML), but led to a pronounced reduction of growth under HL
      conditions, indicating an important photoprotective role of Lut. This was further
      supported by a much higher sensitivity of all Lut-deficient plants to
      photoinhibition in comparison with the wild type. In contrast, replacement of Lut
      by zeaxanthin (Zx) in lut2npq2 led to a pronounced reduction of growth under all
      light regimes, most likely related to the permanent non-photochemical dissipation
      of excitation energy by Zx at Vx-binding sites and the destabilization of antenna
      proteins by binding of Zx to Lut-binding sites. The high susceptibility of
      lut2npq2 to photoinhibition in comparison with npq2 further indicated that the
      photoprotective function of Zx is abolished in the absence of Lut. Thus, it can
      be concluded from our work that neither Vx nor Zx is able to fulfil the essential
      photoprotective function at Lut-binding sites under in vivo conditions.

PMID- 16896792
TI  - NADPH recycling systems in oxidative stressed pea nodules: a key role for the
      NADP+ -dependent isocitrate dehydrogenase.
AB  - The symbiosis between legumes and rhizobia is characterised by the formation of
      dinitrogen-fixing root nodules. In natural conditions, nitrogen fixation is
      strongly impaired by abiotic stresses which generate over-production of reactive
      oxygen species. Since one of the nodule main antioxidant systems is the ascorbate
      glutathione cycle, NADPH recycling that is involved in glutathione reduction is
      of great relevance under stress conditions. NADPH is mainly produced by glucose 6
      phosphate dehydrogenase (G6PDH; EC 1.1.1.49) and 6-phosphogluconate dehydrogenase
      (6PGDH; EC 1.1.1.44) from the oxidative pentose phosphate pathway, and also by
      NADP(+)-dependent isocitrate dehydrogenase (ICDH; EC 1.1.1.42). In this work, 10
      microM paraquat (PQ) was applied to pea roots in order to determine the in vivo
      relationship between oxidative stress and the activity of the NADPH-generating
      enzymes in nodules. Whereas G6PDH and 6PGDH activities remained unchanged, a
      remarkable induction of ICDH gene expression and a dramatic increase of the ICDH
      activity was observed during the PQ treatment. These results support that ICDH
      has a key role in NADPH recycling under oxidative stress conditions in pea root
      nodules.

PMID- 16896793
TI  - Characterization and identification of the candidate gene of rice thermo
      sensitive genic male sterile gene tms5 by mapping.
AB  - Previous research has demonstrated that the thermo-sensitive genic male-sterile
      (TGMS) gene in rice was regulated by temperature. TGMS rice is important to
      hybrid rice production because the application of the TGMS system in two-line
      breeding is cost-effective, simple, efficient and overcomes the limitations of
      the cytoplasmic male sterility (CMS) system. AnnongS is the first discovered and
      deeply studied TGMS rice line in China. Previous studies have suggested that
      AnnongS-1 and Y58S, two derivative TGMS lines of AnnongS, were both controlled by
      a single recessive gene named tms5, which was genetically mapped on chromosome 2.
      In the current study, three populations (AnnongS-1 x Nanjing11, Y58S x Q611, and
      Y58S x Guanghui122) were developed to investigate the tms5 gene molecular map.
      Analysis of recombination events of sterile samples, utilizing 125 probes
      covering the tms5 region, suggested that the tms5 gene was physically mapped to a
      19 kb DNA fragment between two markers, 4039-1 and 4039-2, located on the BAC
      clone AP004039. Following the construction of a physical map between the two
      markers, ONAC023, a member of the NAC (NAM-ATAF-CUC-related) gene family, was
      identified as the candidate of the tms5 gene.

PMID- 16896794
TI  - Genetic and transgenic perturbations of carbon reserve production in Arabidopsis
      seeds reveal metabolic interactions of biochemical pathways.
AB  - The biosynthesis of seed oil and starch both depend on the supply of carbon from
      the maternal plant. The biochemical interactions between these two pathways are
      not fully understood. In the Arabidopsis mutant shrunken seed 1 (sse1)/pex16, a
      reduced rate of fatty acid synthesis leads to starch accumulation. To further
      understand the metabolic impact of the decrease in oil synthesis, we compared
      soluble metabolites in sse1 and wild type (WT) seeds. Sugars, sugar phosphates,
      alcohols, pyruvate, and many other organic acids accumulated in sse1 seeds as a
      likely consequence of the reduced carbon demand for lipid synthesis. The enlarged
      pool size of hexose-P, the metabolites at the crossroad of sugar metabolism,
      glycolysis, and starch synthesis, was likely a direct cause of the increased flow
      into starch. Downstream of glycolysis, more carbon entered the TCA cycle as an
      alternative to the fatty acid pathway, causing the total amount of TCA cycle
      intermediates to rise while moving the steady state of the cycle away from
      fumarate. To convert the excess carbon metabolites into starch, we introduced the
      Escherichia coli starch synthetic enzyme ADP-glucose pyrophosphorylase (AGPase)
      into sse1 seeds. Expression of AGPase enhanced net starch biosynthesis in the
      mutant, resulting in starch levels that reached 37% of seed weight. However,
      further increases above this level were not achieved and most of the carbon
      intermediates remained high in comparison with the WT, indicating that additional
      mechanisms limit starch deposition in Arabidopsis seeds.

PMID- 16896796
TI  - Effects of three AM fungi on growth, distribution of glandular hairs, and
      essential oil production in Ocimum basilicum L. var. Genovese.
AB  - The essential oils of basil are widely used in the cosmetic, pharmaceutical,
      food, and flavoring industries. Little is known about the potential of arbuscular
      mycorrhizal (AM) fungi to affect their production in this aromatic plant. The
      effects of colonization by three AM fungi, Glomus mosseae BEG 12, Gigaspora
      margarita BEG 34, and Gigaspora rosea BEG 9 on shoot and root biomass, abundance
      of glandular hairs, and essential oil yield of Ocimum basilicum L. var. Genovese
      were studied. Plant P content was analyzed in the various treatments and no
      differences were observed. The AM fungi induced various modifications in the
      considered parameters, but only Gi. rosea significantly affected all of them in
      comparison to control plants or the other fungal treatments. It significantly
      increased biomass, root branching and length, and the total amount of essential
      oil (especially alpha-terpineol). Increased oil yield was associated to a
      significantly larger number of peltate glandular trichomes (main sites of
      essential oil synthesis) in the basal and central leaf zones. Furthermore, Gi.
      margarita and Gi. rosea increased the percentage of eugenol and reduced linalool
      yield. Results showed that different fungi can induce different effects in the
      same plant and that the essential oil yield can be modulated according to the
      colonizing AM fungus.

PMID- 16896797
TI  - Wetland dicots and monocots differ in colonization by arbuscular mycorrhizal
      fungi and dark septate endophytes.
AB  - As an initial step towards evaluating whether mycorrhizas influence composition
      and diversity in calcareous fen plant communities, we surveyed root colonization
      by arbuscular mycorrhizal fungi (AMF) and dark septate endophytic fungi (DSE) in
      67 plant species in three different fens in central New York State (USA). We
      found colonization by AMF and DSE in most plant species at all three sites, with
      the type and extent of colonization differing between monocots and dicots. On
      average, AMF colonization was higher in dicots (58+/-3%, mean+/-SE) than in
      monocots (13+/-4%) but DSE colonization followed the opposite trend (24+/-3% in
      monocots and 9+/-1% in dicots). In sedges and cattails, two monocot families that
      are often abundant in fens and other wetlands, AMF colonization was usually very
      low (<10%) in five species and completely absent in seven others. However, DSE
      colonization in these species was frequently observed. Responses of wetland
      plants to AMF and DSE are poorly understood, but in the fen communities surveyed,
      dicots appear to be in a better position to respond to AMF than many of these
      more abundant monocots (e.g., sedges and cattails). In contrast, these monocots
      may be more likely to respond to DSE. Future work directed towards understanding
      the response of these wetland plants to AMF and DSE should provide insight into
      the roles these fungal symbionts play in influencing diversity in fen plant
      communities.

PMID- 16896795
TI  - Pathocycles: Ustilago maydis as a model to study the relationships between cell
      cycle and virulence in pathogenic fungi.
AB  - Activation of virulence in pathogenic fungi often involves differentiation
      processes that need the reset of the cell cycle and induction of a new
      morphogenetic program. Therefore, the fungal capability to modify its cell cycle
      constitutes an important determinant in carrying out a successful infection. The
      dimorphic fungus Ustilago maydis is the causative agent of corn smut disease and
      has lately become a highly attractive model in addressing fundamental questions
      about development in pathogenic fungi. The different morphological and genetic
      changes of U. maydis cells during the pathogenic process advocate an accurate
      control of the cell cycle in these transitions. This is why this model pathogen
      deserves attention as a powerful tool in analyzing the relationships between cell
      cycle, morphogenesis, and pathogenicity. The aim of this review is to summarize
      recent advances in the unveiling of cell cycle regulation in U. maydis. We also
      discuss the connection between cell cycle and virulence and how cell cycle
      control is an important downstream target in the fungus-plant interaction.

PMID- 16896798
TI  - Molecular characterization and evaluation of mycorrhizal capacity of Suillus
      isolates from central Spain for the selection of fungal inoculants.
AB  - Suillus fungal specimens of pine forests from a Mediterranean area of central
      Spain (Madrid region) were studied based on molecular and physiological analysis
      of sporocarps to obtain fungal native inocula to produce mycorrhizal Pinus
      halepensis Miller in nursery. Variation within the internal transcribed spacer
      (ITS) region of the ribosomal RNA genes of Suillus was examined by restriction
      fragment length polymorphism (RFLP) and direct sequencing of polymerase chain
      reaction products. Ribosomal DNA (rDNA) spacers were amplified from pure cultures
      obtained from fruit bodies of a range of Suillus species: Suillus bellinii
      (Inzenga) Watling, Suillus bovinus (Pers.) Kuntze, Suillus collinitus (Fr.)
      Kuntze, Suillus granulatus (L.) Snell, Suillus mediterraneensis (Jacquet. & Blum)
      Redeuil, Suillus luteus L. (Gray), and Suillus variegatus (Sw.) Kuntze.
      Interspecific variation in the length and number of restriction sites of the
      amplified ITS region was observed. This variation was confirmed by sequencing,
      which allowed us to identify some isolates. This is the first time that the ITS
      sequence of S. mediterraneensis is completely described. No intraspecific rDNA
      variation was observed within isolates of S. collinitus, S. mediterraneensis, and
      S. luteus. The phylogenetic analysis established the close relationship among
      these Mediterranean fungal species. As a further step to characterize the
      different isolates and to understand the relation between genetic and functional
      diversity, some physiological variables were evaluated. Intraspecific variation
      in axenic fungal growth and in mycorrhizal capacities was detected, especially
      within S. collinitus isolates. The fungal isolates stimulated the growth of P.
      halepensis in different rates. These studies indicated that ITS analysis, in
      conjunction with mycorrhizal tests, provides suitable combined tools for the
      analysis of Suillus spp. in a small geographic area for selecting isolates with
      final afforestation purposes.

PMID- 16896799
TI  - Lunularia cruciata, a potential in vitro host for Glomus proliferum and G.
      intraradices.
AB  - A study was conducted to define culture conditions for in vitro growth arbuscular
      mycorrhizal fungi (AMF) with liverworts as hosts. Lunularia cruciata (L.)
      Dumortier ex. Lindberg developed in vitro monoxenic mycothalli with both Glomus
      proliferum Dalpe & Declerck (MUCL 41827) and Glomus intraradices Schenck & Smith
      (MUCL 43204). AMF inoculated plants were co-cultured in plastic Petri dishes with
      semi-solidified medium supplemented with sucrose and grown under filtered light.
      Mycothalli of L. cruciata produced external hyphae and spores in quantities
      equivalent to those obtained with Ri T-DNA transformed root systems.

PMID- 16896800
TI  - An overview of Cistus ectomycorrhizal fungi.
AB  - The genus Cistus comprises a group of about 20 shrub species found in wide areas
      throughout the whole Mediterranean region to the Caucasus. Being one of the main
      constituents of the Mediterranean-type maquis, this plant genus is peculiar in
      that it has developed a range of specific adaptations to resist summer drought
      and frequent disturbance events, such as fire and grazing. In addition, it can
      form both ectomycorrhizas and arbuscular mycorrhizas. In this paper, we review
      the information available on the ectomycorrhizal fungi of Cistus across its
      entire geographic range, as gathered and critically sifted from both published
      literature sources and personal observations. Although the resulting data matrix
      was based primarily on accounts of sporocarp inventories in the field, existing
      knowledge on the features of Cistus natural and synthesized ectomycorrhizas was
      also included and discussed. In total, more than 200 fungal species belonging to
      40 genera have been reported so far to be associated with Cistus. An analysis of
      the pattern of ectomycorrhizal diversity and host specificity revealed that
      members of the Cortinariaceae and Russulaceae make the most of both Cistus
      aspecific and Cistus-specific mycobionts. Further studies are needed to expand
      our preliminary knowledge of the mycorrhizal ecology and biology of Cistus and
      its fungal associates, focusing on topics such as mycobiont diversity, host
      specificity, fungal succession, mycorrhizal influence on stress tolerance, and
      impact of disturbances, while comparing the findings with those from other
      ecosystems.

PMID- 16896801
TI  - Enhancement of vascular smooth muscle cell migration by urotensin II.
AB  - The effects of urotensin II (UII) on migration of human aortic smooth muscle
      cells (HASMCs) were investigated. UII (1-100 nM) significantly increased velocity
      of HASMC motility in a concentration-dependent manner. Stress-fiber formation and
      ERK (p44/p42) activity were also increased by UII. U0126 and PD 98059, MEK
      inhibitors, abolished the effects of UII on motility velocity and stress-fiber
      formation. These results suggest that UII enhances HASMC migration through
      activation of an ERK-dependent pathway.

PMID- 16896802
TI  - Effect of endothelin-1 on erythropoietin production in a rat model under normoxia
      and functional carbon monoxide-induced hypoxia.
AB  - It has been hypothesized that autacoids, such as endothelin-1 (ET), may modulate
      erythropoietin (Epo) secretion. Therefore, we studied the effect of ET-1 infusion
      and of a nonselective ET(A/B) receptor antagonist on Epo secretion under carbon
      monoxide (CO) exposure. Anesthetized rats were supplied with room temperature air
      containing increasing concentrations of CO by an aerating cap. A CO-Epo dose
      response curve over the range of 0.02-0.14 vol% CO was conducted. Subpressor
      doses of ET-1 (3 pmol/min/kg BW) and the ET(A/B) receptor antagonist LU302872
      (LU; 30 mg/kg) were applied to anaesthetized rats under normoxia (controls CON,
      ET, LU) and following hypoxia (CO exposure; H-CON, H-ET, H-LU). Mean arterial
      blood pressure (MAP), glomerular filtration rate (GFR, inulin clearance), Epo and
      ET-1 serum concentrations (ELISA) and renal Epo mRNA (Light Cycler) were
      determined. The EC50 value for CO was 0.1 vol% with a 70-fold increase in Epo
      serum concentrations. CO exposure increased Epo serum and Epo mRNA concentrations
      in the expected range in all groups. None of the treatments with ET or LU
      influenced the effect of hypoxia on Epo serum concentrations and renal Epo mRNA
      content. Under hypoxia, administration of ET-1 as well as LU prevented the
      hypoxia-induced decrease in MAP (p<0.05). Under hypoxia, GFR was reduced by 50%
      except for H-LU with values comparable to normoxia. Taken together, the influence
      of hypoxia exceeds by far the effect of ET-1 on Epo production, irrespective of
      the presence or absence of exogenous ET-1. Thus, ET-1 does not appear to be a
      major modulator of Epo production.

PMID- 16896803
TI  - Anti-inflammatory effect of intravenous immunoglobulin in comparison with
      dexamethasone in vitro: implication for treatment of Kawasaki disease.
AB  - High-dose intravenous immunoglobulin (IVIG) is a well-established standard
      therapy for Kawasaki disease (KD) that reduces the risk of developing coronary
      artery aneurysms. On the other hand, some reports have recommended an alternative
      therapy with steroids for KD patients. In this study we investigated the anti
      inflammatory effect of IVIG in comparison with dexamethasone at clinical doses in
      vitro. High-dose IVIG inhibited tumor necrosis factor-alpha (TNF-alpha)-induced
      activation of nuclear factor-kappaB (NF-kappaB) to a greater degree than
      dexamethasone in human monocytic U937 cells and human coronary arterial
      endothelial cells (HCAEC), but not in human T lymphocytic Jurkat cells. IVIG was
      more potent than dexamethasone in reducing the expression of CD16 (FcgammaRIII)
      in human monocytic THP-1 cells stimulated with lipopolysaccharide and in Jurkat
      cells stimulated with dimethyl sulfoxide. In HCAEC exposed to TNF-alpha, IVIG and
      dexamethasone inhibited interleukin-6 production to a similar degree, whereas the
      expression of E-selectin was inhibited more strongly by IVIG. Our results show
      that high-dose IVIG inhibits the activation of monocytes/macrophages and coronary
      arterial endothelial cells more strongly than that of T cells, whereas
      dexamethasone inhibits the activation of all three cell types. These findings
      suggest that IVIG or dexamethasone therapy should be chosen to match the types of
      cells that are activated during acute KD.

PMID- 16896804
TI  - Gef10--the third member of a Rho-specific guanine nucleotide exchange factor
      subfamily with unusual protein architecture.
AB  - According to cDNA sequence homologies, Gef10 is related to the Rho-specific
      guanine nucleotide exchange factors GrinchGEF and p164-RhoGEF. Like these GEFs,
      Gef10 exhibits only weak homology to known pleckstrin homology domains, but
      contains a putative WD40-like domain. As detected by RT-PCR, Gef10 is transcribed
      in at least two splice variants in different human tissues. Although the Gef10
      sequence contains two putative transmembrane segments, recombinantly expressed
      Gef10 displays a cytosolic localisation. As detected by guanine nucleotide
      exchange activity assay, precipitation assay of GTP-bound Rho proteins and serum
      response element dependent gene transcription Gef10 activates RhoA-C, but not
      Rac1 or Cdc42. In the reporter gene assay, Gef10 preferentially activated RhoB.
      When expressed in NIH3T3 cells, Gef10 induced actin stress fibre, but not
      lamellipodia or filopodia formation. We conclude that Gef10 is the third member
      of a Rho-specific GEF family with unusual protein architecture.

PMID- 16896806
TI  - Nucleotides and inorganic phosphates as potential antioxidants.
AB  - Highly reactive OH radicals, formed in an iron-ion catalyzed Fenton reaction, are
      implicated in many pathological conditions. The quest for Fenton reaction
      inhibitors, either radical scavenger or metal-ion chelator antioxidants, spans
      the previous decades. Purine nucleotides were previously studied as natural
      modulators of the Fenton reaction; however, the modulatory role of purine
      nucleotides remained in dispute. Here, we have resolved this long-standing
      dispute and demonstrated a concentration-dependent biphasic modulation of the
      Fenton reaction by nucleotides. By electron spin resonance measurements with 0.1
      mM Fe(II), we observed an increase of *OH production at low purine nucleotide
      concentrations (up to 0.15 mM), while at higher nucleotide concentrations, an
      exponential decay of *OH concentration was observed. We found that the phosphate
      moiety, not the nucleoside, determines the pro/antioxidant properties of a
      nucleotide, suggesting a chelation-based modulation. Furthermore, the biphasic
      modulation mode is probably due to diverse nucleotide-Fe(II) complexes formed in
      a concentration-dependent manner. At ATP concentrations much greater than Fe(II)
      concentrations, multiligand chelates are formed which inhibit the Fenton reaction
      owing to a full Fe(II) coordination sphere. In addition to natural nucleotides,
      we investigated a series of base- or phosphate-modified nucleotides,
      dinucleotides, and inorganic phosphates, as potential biocompatible antioxidants.
      Ap5A, inorganic thiophosphate and ATP-gamma-S proved highly potent antioxidants
      with IC50 values of 40, 30, and 10 microM, respectively. ATP-gamma-S proved 100
      and 20 times more active than ATP and the potent antioxidant Trolox,
      respectively. In the presence of 30 microM ATP-gamma-S no *OH was detected after
      5 min in the Fenton reaction mixture. The most potent antioxidants identified
      inhibit the Fenton reaction by forming full coordination sphere chelates.

PMID- 16896805
TI  - The HMG-CoA reductase inhibitor, pravastatin, prevents the development of
      monocrotaline-induced pulmonary hypertension in the rat through reduction of
      endothelial cell apoptosis and overexpression of eNOS.
AB  - HMG-CoA reductase inhibitors improve endothelial function and exert
      antiproliferative effects on vascular smooth muscle cells of systemic vessels.
      This study was aimed to assess the protective effects of pravastatin (an HMG-CoA
      reductase inhibitor) against monocrotaline-induced pulmonary hypertension in
      rats. Pravastatin (PS, 10 mg/kg/day) or vehicle were given orally for 28 days to
      Wistar male rats injected or not with monocrotaline (MC, 60 mg/kg
      intraperitonealy) and treated or not by N(omega)-nitro-L-arginine methyl ester (L
      NAME) 15 mg/kg/day. At 4 weeks, monocrotaline-injected rats developed severe
      pulmonary hypertension, with an increase in right ventricular pressure (RVP) and
      right ventricle/left ventricle+septum weight ratio (RV/LV+S), associated with a
      decrease in pulmonary artery dilation induced either by acetylcholine or sodium
      nitroprusside. Hypertensive pulmonary arteries exhibited an increase in medial
      thickness, medial wall area, endothelial cell apoptosis, and a decrease of
      endothelial nitric oxide synthase (eNOS) expression. Monocrotaline-rat lungs
      showed a significant decrease of eNOS expression (4080+/-27 vs 12189+/-761
      arbitrary density units [ADU] for MC and control groups respectively, P<0.01) and
      a significant increase of cleaved caspase-3 expression by western blotting
      (Control=11628+/-2395 vs MC=2326+/-2243 ADU, P<0.05). A non-significant trend
      toward a reduced mortality was observed with pravastatin (relative risk of death
      = 0.33; 95% confidence interval [0.08-1.30], P= 0.12 for MC+PS vs MC groups).
      Pravastatine induced a protection against the development of the pulmonary
      hypertension (RVP in mmHg: 30+/-3 vs 45+/-4 and RV/LV+S: 0.46+/-0.04 vs 0.62+/
      0.05 for MC+PS and MC groups respectively, P<0.05) and was associated with a
      significant reduction of MC-induced thickening (61+/-6 mum vs 81+/-3 mum for
      MC+PS and MC groups respectively, P= 0.01) of the medial wall of the small
      intrapulmonary arteries. Pravastatin partially restored acetylcholine-induced
      pulmonary artery vasodilation in MC rats (Emax=65+/-5% and 46+/-3% for MC+PS and
      MC group respectively, P<0.05) but had no effect on acetylcholine-induced
      pulmonary artery vasodilation in MC+L-NAME rats. It also prevented apoptosis and
      restored eNOS expression of pulmonary artery endothelial cells, as well as in the
      whole lung. Pravastatin reduces the development of monocrotaline-induced
      pulmonary hypertension and improves endothelium-dependent pulmonary artery
      relaxation, probably through a reduced apoptosis and a restored eNOS expression
      of endothelial cells.

PMID- 16896808
TI  - Recurrent ileocolic intussusception after different surgical procedures in
      children.
AB  - Intussusception in children may recur after surgical correction. Ileopexy has
      popularly been used as a procedure to prevent recurrent intussusception, but its
      effect has not been well evaluated. The present study compared the incidence of
      recurrent intussusception after several different surgical procedures for
      intussusception in children. The charts of 278 children undergoing surgical
      reduction of ileocolic intussusception over 17 years were retrospectively
      reviewed. The incidence of recurrent intussusception was compared among the three
      surgical procedures: simple manual reduction, manual reduction plus ileopexy, and
      segmental resection. Simple manual reduction was performed in 67 (24.1%) of the
      278 patients, manual reduction plus ileopexy in 186 (66.9%), and resection of the
      involved segment in 25 (9.0%). There were four episodes of recurrence in three
      (4%) patients who had had manual reduction, nine episodes in eight (4%) patients
      who had undergone ileopexy, and none after segmental resection. There was no
      statistical difference in recurrent rate among the three groups (reduction vs.
      ileopexy, P = 0.95; reduction vs. resection, P = 0.28; ileopexy vs. resection, P
      = 0.29). Ileopexy is not better than simple manual reduction in preventing
      recurrence of ileocolic intussusception in children.

PMID- 16896807
TI  - Ferritin-catalyzed consumption of hydrogen peroxide by amine buffers causes the
      variable Fe2+ to O2 stoichiometry of iron deposition in horse spleen ferritin.
AB  - Ferritin catalyzes the oxidation of Fe2+ by O2 to form a reconstituted Fe3+ oxy
      hydroxide mineral core, but extensive studies have shown that the Fe2+ to O2
      stoichiometry changes with experimental conditions. At Fe2+ to horse spleen
      ferritin (HoSF) ratios greater than 200, an upper limit of Fe2+ to O2 of 4 is
      typically measured, indicating O2 is reduced to 2H2O. In contrast, a lower limit
      of Fe2+ to O2 of approximately 2 is measured at low Fe2+ to HoSF ratios,
      implicating H2O2 as a product of Fe2+ deposition. Stoichiometric amounts of H2O2
      have not been measured, and H2O2 is proposed to react with an unknown system
      component. Evidence is presented that identifies this component as amine buffers,
      including 3-N-morpholinopropanesulfonic acid (MOPS), which is widely used in
      ferritin studies. In the presence of non-amine buffers, the Fe2+ to O2
      stoichiometry was approximately 4.0, but at high concentrations of amine buffers
      (0.10 M) the Fe2+ to O2 stoichiometry is approximately 2.5 for iron loadings of
      eight to 30 Fe2+ per HoSF. Decreasing the concentration of amine buffer to zero
      resulted in an Fe2+ to O2 stoichiometry of approximately 4. Direct evidence for
      amine buffer modification during Fe2+ deposition was obtained by comparing
      authentic and modified buffers using mass spectrometry, NMR, and thin layer
      chromatography. Tris(hydroxymethyl)aminomethane, MOPS, and N-methylmorpholine (a
      MOPS analog) were all rapidly chemically modified during Fe2+ deposition to form
      N-oxides. Under identical conditions no modification was detected when amine
      buffer, H2O2, and O2 were combined with Fe2+ or ferritin separately. Thus, a
      short-lived ferritin intermediate is required for buffer modification by H2O2.
      Variation of the Fe2+ to O2 stoichiometry versus the Fe2+ to HoSF ratio and the
      amine buffer concentration are consistent with buffer modification.

PMID- 16896809
TI  - Hepatic damage in biliary-obstructed rats is ameliorated by leflunomide
      treatment.
AB  - Cholestasis, or impaired bile flow, occurs in a wide variety of liver diseases
      and causes hepatic damage by retention and accumulation of toxic hydrophobic bile
      salts inducing persistent inflammation and oxidative stress. In the present
      research, we studied the effect of leflunomide, a novel immunosuppressive and
      anti-inflammatory agent against autoimmune disease, on hepatic damage produced by
      double ligature of the extrahepatic biliary duct in Wistar Albino rats.
      Cholestasis was done by double ligature and section of the extrahepatic biliary
      duct (BDL). Leflunomide was given i.g. 10 mg/kg/day. The severity of cholestasis
      and hepatic injury was determined by changes in the plasma enzyme activities of
      alanine aminotransferase (ALT), aspartate aminotransferase (AST) and levels of
      direct bilirubin. Malondialdehyde (MDA), protein carbonyl (PC), nitric oxide
      (NO), catalase (CAT) and superoxide dismutase (SOD) were determined to the
      oxidative status in the liver tissue. Myeloperoxidase (MPO) activity and levels
      of tissue hydroxyproline (HPR) were determined to neutrophil activation and
      collagen accumulation, respectively. Further, histological changes were studied.
      Treatment with leflunomide markedly reduced serum transaminase activities as
      compared to BDL rats. At the same time leflunomide significantly inhibited
      increases in liver MDA, PC and NO levels and also attenuated the depletion of CAT
      and SOD in the liver after bile duct ligation. Similarly, increase in tissue MPO
      activity and HPR due to BDL was also attenuated by leflunomide treatment. These
      findings were supported by histopathological findings. These findings suggested
      that leflunomide can attenuate hepatic damage in extrahepatic cholestasis by
      prevention of oxidative stress and inflammatory process.

PMID- 16896810
TI  - Hepatogastric fistula in a pediatric patient.
AB  - Hepatogastric fistula secondary to amebic liver abscess is extremely rare. Only
      three pediatric cases have been reported in the English literature. Percutaneous
      drainage of abscess along with parenteral metronidazole can prevent the need for
      extensive surgical intervention. Timely intervention is usually followed by
      complete recovery.

PMID- 16896812
TI  - Symptomatic spontaneous pneumothorax in term newborns.
AB  - The causes and risk factors of symptomatic spontaneous pneumothorax in term
      newborns are not completely understood. In the present study, our aim was to
      investigate the risk factors for and clinical and laboratory characteristics of
      term newborns with spontaneous symptomatic pneumothorax and to evaluate the
      outcome of management in this condition. A total of 11 term newborns admitted to
      the newborn intensive care unit with a diagnosis of symptomatic spontaneous
      pneumothorax were included during a 22-month period. Female to male ratio was
      4:7, mean gestational age was 39.5 weeks, and 63% were delivered with a cesarean
      section, 18% of patients had renal and 55% had congenital cardiac anomalies. Rate
      of cardiac anomalies was more frequent in the study group compared to control
      group. Echocardiography in addition to renal ultrasonography may also be needed
      in term newborns with spontaneous symptomatic pneumothorax and further studies
      may be warranted to evaluate this association.

PMID- 16896811
TI  - Bladder exstrophy and epispadias complex in sibling: case report and review of
      literature.
AB  - The bladder exstrophy and classic epispadias represent a spectrum of congenital
      anomalies with different degrees of anterior midline defect. Although the anomaly
      usually occurs sporadically there are some cases indicative of a strong genetic
      component. We present the clinical data of two siblings with bladder exstrophy
      and epispadias complex (BEEC), who were the product of consanguineous union. All
      previous reports of familial BEEC in the literature have been reviewed.

PMID- 16896813
TI  - Single stage Fowler-Stephens orchidopexy: a preferred alternative in the
      treatment of nonpalpable testes.
AB  - In this present study we aimed to discuss the surgical efficacy of single stage
      Fowler-Stephens orchidopexy (FSO) technique, with an emphasis on its practical
      and logical application that may be kept in mind during a standard orchidopexy
      procedure. Twenty-two children have undergone a single stage FSO procedure for
      nonpalpable testes during the last 9 years in our department. Surgical procedure
      was initiated with a standard inguinal oblique incision keeping in mind that
      depending on the position and the anatomic features of the testes a FSO method
      might be needed. While an excellent result was defined as a testis with good
      scrotal position, size and adequate blood flow on Doppler sonogram, acceptable
      result was a palpably normal sized testis in a high scrotal position with
      adequate blood supply and lastly an unacceptable result was the atrophy of the
      testis with compromised blood supply. During regular follow-up visits although
      some cases revealed testicular atrophy; long-term examination (12 months) did
      show that majority of the testes maintained their normal position and tissue
      consistency (21/24, 87.5%). Due to the necessity of surgical approach either in
      the evaluation or the treatment of nonpalpable testes in most cases along with
      the unsatisfactory data of the time consuming and invasive radiological
      procedures; we believe that a classical orchidopexy approach together with
      further single stage FSO will be a rational and satisfactory algorithm in the
      majority of such cases.

PMID- 16896814
TI  - Paraesophageal bronchogenic cyst: first case reports in pediatric.
AB  - We described for the first time a paraesophageal intra-abdominal bronchogenic
      cyst, first considered as hepatic tumor, in a young boy. Resection was
      successfully realized by laparoscopy. Abdominal bronchogenic cyst and
      differential diagnosis are discussed.

PMID- 16896815
TI  - Does the pediatric end-stage liver disease score or hepatic artery resistance
      index predict outcome after liver transplantation for biliary atresia?
AB  - The pediatric end-stage liver disease score (PELD) was devised and validated as a
      tool for predicting mortality and morbidity in children with chronic liver
      disease waiting for a liver transplant (LT). It has become a useful guide for
      prioritizing organ allocation in the United States. The hepatic artery resistance
      index (HARI) also predicts waiting list mortality in children with biliary
      atresia. Does the PELD score or HARI predict outcome after LT for biliary
      atresia? Twenty consecutive children who underwent LT for biliary atresia between
      2001 and 2005 were reviewed. Their PELD score was calculated periodically between
      listing and transplantation and HARI was measured at listing. Outcome variables
      were operative blood transfusion requirements, ICU stay and postoperative stay.
      Median age at LT was 8 (2-204) months. After allowing for the type of graft, the
      PELD score and the change in PELD score between listing and LT (deltaPELD) showed
      no significant correlation with blood transfusion requirements, but both the PELD
      score at listing and deltaPELD showed a trend toward a statistically significant
      positive correlation with overall hospital stay. Pre-transplant HARI showed a
      statistically significant positive correlation with the PELD score at listing (r
      = 0.46, p = 0.05) but did not correlate significantly with hospital stay. In this
      relatively small but homogeneous group of children undergoing LT for biliary
      atresia, PELD, and deltaPELD scores showed a trend toward a statistically
      significant positive correlation with overall hospital stay. However, neither
      PELD scores nor the pre-transplant HARI showed a definite correlation with
      outcome. Post-transplant complications are probably more important factors
      determining ICU and hospital stay in children currently transplanted for biliary
      atresia.

PMID- 16896817
TI  - A case of pancreatoblastoma prenatally diagnosed as intraperitoneal cyst.
AB  - Pancreatoblastoma in childhood is a very rare malignant tumor, but is considered
      to have a relatively good prognosis because of its low metastatic potential. We
      report 1-day-old female infant who was recently found to have an intraabdominal
      cyst on prenatal ultrasound examination. The tumor was a unilocular, cystic mass
      without invasion or metastasis to other organs, allowing total resection. It was
      diagnosed postnatally with pancreatoblastoma.

PMID- 16896818
TI  - A hepaticojejunostomy: technical errors with 'twists and turns'.
AB  - Excision of a choledochal cyst followed by biliary reconstruction with a Roux-en
      Y hepaticojejunostomy is the treatment of choice for type I and IV choledochal
      cysts. We present a rare complication which was identified 8 years after the
      original reconstructive surgery. Conventional imaging modalities failed to
      identify the pathology. Only a contrast enhanced CT scan supported by image
      rendering software allowed for the visualization of the underlying chronic
      obstruction of part of the mesentery.

PMID- 16896816
TI  - Effects of dexamethasone on small bowel and kidney oxidative stress and
      histological alterations in bile duct-ligated rats.
AB  - Oxidative stress plays an important role in the pathogenesis of toxic liver
      diseases and other hepatic alterations including obstruction of bile flow. It has
      been shown that the gastrointestinal tract and renal tissue is particularly
      affected during obstruction of bile flow. In this study, we aimed to evaluate the
      effects of dexamethasone on small bowel and kidney oxidative stress and
      histological alterations in bile duct-ligated (BDL) rats. A total of 40 male
      Sprague-Dawley rats weighing 200-240 g were used in this study. Group 1 (Sham
      control, n = 10) rats underwent laparotomy and bile duct was dissected from the
      surrounding tissue. Group 2 (Dexa-control, n = 10) rats underwent laparotomy and
      bile duct was dissected from the surrounding tissue. The rats received daily
      dexamethasone. Group 3 (BDL/Untreated, n = 10) rats were subjected to bile duct
      ligation and no drug was applied. Group 4 (BDL/Dexa, n = 10) rats received daily
      dexamethasone by orogastric tube for 14 days after BDL. At the end of the 2-week
      period, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH
      Px), and malondialdehyde (MDA) were measured and biochemical and histological
      evaluation were processed. The mean serum bilirubin, liver enzymes, MDA level,
      and histopathological score significantly decreased and SOD, CAT, and GSH-Px
      values were significantly increased in group 4 when compared to group 3. Group 3
      presented a significant increase in caecal count of E. coli and in
      aerobe/anaerobe ratio. In group 4, liver was moderately damaged. Ileal biopsies
      from group 4 demonstrated a significant increase in villus height, total mucosal
      thickness, and villus density when compared to group 3. Glomerular injury scores
      (GIS) and arterial injury scores (AIS) in group 3 rats were increased in the
      juxtamedullary region. In contrast to group 4, tubulo-interstitial lesions were
      diffuse in group 3 animals. Dexamethasone reduced small bowel and kidney
      oxidative stress and histological alterations in bile duct-ligated rats with
      increasing SOD, CAT, and GSH-Px and decreasing MDA levels in rats with obstructed
      bile duct.

PMID- 16896819
TI  - Optimizing vector application for gene transfer into human hepatoblastoma cells.
AB  - Gene targeting is currently of distinct interest as an innovative additive
      treatment option in various malignancies. Its role in pediatric liver tumors has
      not yet been evaluated thoroughly. For the first time the authors systematically
      analyzed both lipid-based transfection as well as transduction with adenovirus
      vectors (Ad) and Sendai virus vectors (SeVV) in order to optimize gene transfer
      into hepatoblastoma (HB) cells. Two HB cell lines were infected with Ad or SeVV
      coding for green fluorescent protein (Ad-GFP, SeVV-GFP); transduction
      efficiencies and apoptosis were assessed using flow cytometry. Furthermore,
      lipofection of HB cell lines with plasmid-constructs comprising liver-specific
      promoters was performed using Lipofectamine 2000 and FuGENE 6; lipofection
      efficiency was monitored by flow cytometry, microscopy, and luciferase activity.
      The Ad-GFP showed higher transduction rates (61-86%) than the SeVV-GFP (4-24%)
      depending on the HB cell line used. Infections with first generation SeVV vectors
      (SeVV-GFP) led to increased target cell apoptosis (7-43%) compared to Ad-GFP (4
      16%). The Lipofectamine 2000 revealed a higher transfection efficiency than the
      FuGENE 6 for both HB cell lines tested. The liver-specific promoters were found
      to be differently active in the HB cell lines. This study delineates recombinant
      adenovirus vectors as a promising tool for gene transduction in the HB cells.
      Furthermore, enhanced activity of the liver-specific promoters in HUH6 cells
      compared to HepT1 cells supports the observation of varying biological behavior
      in histologically differing HB tissues.

PMID- 16896820
TI  - Lytic rib lesion in a 1-year-old child: group A beta streptococcal osteomyelitis
      mimicking tumor.
AB  - Pediatric osteomyelitis commonly occurs in the long bones and has rarely been
      reported in small bones such as the vertebrae and ribs. Rib osteomyelitis occurs
      in approximately 1% or less of all cases of hematogenous osteomyelitis, and is
      usually caused by Staphylococcus aureus. We present a case of acute osteomyelitis
      in the rib of an otherwise healthy and afebrile 1-year-old infant that appeared
      as a lytic bone lesion on imaging studies and was mistaken for a tumor. Biopsy
      was needed to rule out malignancy and establish the diagnosis of osteomyelitis
      caused by group A Streptococcus. This is one of the few reported cases of
      pediatric rib osteomyelitis caused by this organism.

PMID- 16896821
TI  - Use of cultures in cellulitis: when, how, and why?

PMID- 16896822
TI  - Addition of a macrolide to a ss-lactam in bacteremic pneumococcal pneumonia.
AB  - In the study presented here, data collected prospectively from 340 adult patients
      hospitalised in five countries with bacteremic pneumococcal CAP and treated with
      a ss-lactam +/- a macrolide were analysed retrospectively to evaluate the
      efficacy of this antimicrobial combination. Univariate and multivariate analyses
      revealed no significant effect on case fatality rate when a macrolide/ss-lactam
      regimen was used as initial therapy. Results were not affected by severity of
      illness, or by excluding patients who died within 2 days of admission. Identified
      predictors of death in a multivariate regression model were age >65 years
      (OR=2.6), two or more lung lobes affected (OR=2.2), and severity of disease as
      estimated using the acute physiology score (APS)>8.

PMID- 16896823
TI  - Elevated procalcitonin as a diagnostic marker in meningococcal disease.
AB  - Patients with meningococcal disease who seek medical attention can create a
      diagnostic dilemma for clinicians due to the nonspecific nature of the disease's
      presentation. This study assesses the diagnostic accuracy of procalcitonin levels
      in the setting of meningococcal disease. Two emergency department cohorts (A and
      B) were studied between 2002 and 2005, during the current epidemic of serogroup B
      meningococcal disease in New Zealand. Cohort A consisted of 171 patients, all
      with confirmed meningococcal disease (84 children, 87 adults). Cohort B consisted
      of a large (n=1,524) consecutively recruited population of febrile patients who
      presented to the emergency department, 28 of whom had confirmed meningococcal
      disease. Within the meningococcal disease cohort (cohort A), the geometric mean
      procalcitonin level was 9.9 ng/ml, with levels being higher in children than in
      adults (21.6 vs. 4.6 ng/ml, p=0.01). The overall sensitivity of elevated
      procalcitonin, using a cutoff of 2.0 ng/ml in children and 0.5 ng/ml in adults,
      was 0.93 (95%CI: 0.88-0.96). Despite the higher cutoff level for paediatric
      patients, a trend towards greater sensitivity existed in children (0.96 vs. 0.90;
      p=0.08). Elevated procalcitonin was correlated with whole blood meningococcal
      load (r=0.50) and Glasgow Meningococcal Sepsis Prognostic Score (r=0.40). Within
      the cohort of patients who were febrile on presentation (cohort B), the
      specificity of elevated procalcitonin in meningococcal disease was 0.85 (95% CI:
      0.83-0.87), the positive and negative likelihood ratios were 6.1 and 0.08,
      respectively, and the sensitivity of elevated procalcitonin (0.93; 95% CI: 0.76
      0.99) was corroborated. Measurement of procalcitonin is a useful tool in patients
      with nonspecific febrile illnesses when the possibility of meningococcal disease
      is present. The diagnostic accuracy surpasses that of current early laboratory
      markers, allowing results to be used to guide decisions about patient management.

PMID- 16896824
TI  - Carriage of Streptococcus pneumoniae in healthy Norwegian children attending day
      care centres.
AB  - An observational study to examine Streptococcus pneumoniae carriage in Norwegian
      children was initiated after two cases of pneumococcal meningitis, caused by the
      England(14)-9 clone, occurred in one day-care centre in Oslo. All children
      recruited from the day-care centre where the cases occurred were vaccinated with
      a seven-valent pneumococcal conjugate vaccine; the other participants who
      attended three other day-care centres nearby were not. The children were followed
      for 9 months, and three samplings took place. At the first visit, 45.7% of the
      children were colonised by pneumococci in the nasopharynx. The children harboured
      a variety of serotypes, with serotypes 6A, 23F, 6B and 19F being the most
      frequent. The numbers of children carrying vaccine serotypes decreased in both
      the vaccinated and the non-vaccinated groups. Thus, no significant effect of
      vaccine on carriage was detected in this relatively small study.

PMID- 16896825
TI  - In vitro antimicrobial activity of moxifloxacin against bacterial strains
      isolated from blood of neutropenic cancer patients.

PMID- 16896826
TI  - Wild boars as possible source of hemorrhagic leptospirosis in Berlin, Germany.

PMID- 16896827
TI  - Changing trends in etiology of bacteremia in patients with cancer.
AB  - The present study was conducted to determine trends in the quantitative bacterial
      load patterns of bacterial bloodstream infections (BSI) caused by various
      bacteria in patients receiving care at a comprehensive cancer center. Bacterial
      loads of all consecutive quantitative blood cultures performed during 1998 and
      2004 were graded quantitatively. Gram-positive bacteria (GPB) were responsible
      for the majority of BSI episodes in both years studied: 740 of 1,055 (73%) in
      1998 and 820 of 1,025 (82%) in 2004. Compared with GPB infections, a significant
      proportion of infections caused by Gram-negative bacteria was associated with a
      high bacterial load (HBL) (11 vs 28% in 1998 and 10 vs 30% in 2004; p<0.001). In
      2004, BSI episodes due to non-Pseudomonas non-fermentative GNB (Stenotrophomonas
      maltophilia and Acinetobacter spp) were significantly associated with a HBL
      compared to BSI due to Pseudomonas aeruginosa (47 vs 23%; p<0.05); this was not
      the case in 1998. Conversely, the HBLs commonly associated with BSI due to
      Staphylococcus aureus (50%) and Streptococcus spp (35%) versus coagulase-negative
      staphylococci (13%; p<0.0001) during 1998 were not noted during 2004 (22%
      Staphylococcus aureus, 20% Streptococcus spp, 21% coagulase-negative
      staphylococci; p>0.5). The spectrum of BSI continues to change and its prognostic
      implications in cancer patients needs further study.

PMID- 16896828
TI  - Longitudinal study of patients after surgical treatment for cervical lesions:
      detection of HPV DNA and prevalence of HPV-specific antibodies.
AB  - The principal aims of this study were to test whether persistence of human
      papillomavirus (HPV) DNA is predictive of recurrent disease in women after
      surgical treatment for cervical lesions, to distinguish between persistent and
      newly acquired HPV infection, and to observe the effect of surgical treatment on
      levels of HPV-specific antibodies. A group of 198 patients surgically treated for
      low-grade and high-grade squamous intraepithelial lesions and 35 age-matched
      controls were monitored for 18 months at 6-month intervals. The presence of HPV
      DNA in cervical smears was detected by means of consensus polymerase chain
      reaction, and serum levels of HPV-specific antibodies to HPV types 16, 18, 31,
      33, and 45 were measured. In ten patients positive for HPV type 16 in consecutive
      samples, the HPV 16 variants were identified using a polymerase chain reaction
      specific for the long control region. Data regarding demographics, risk factors
      for cervical cancer, and risks related to HPV exposure were collected through a
      patient questionnaire. Subjects persistently positive for HPV DNA were more
      likely to present with cytological and/or colposcopical abnormalities. A higher
      reactivity to HPV-specific antibodies was observed in these women at the 18-month
      follow-up visit. All ten patients with HPV 16 infection detected in consecutive
      samples showed persistence of either the same prototype or the same variant
      during the follow-up period. Risky sexual behavior and smoking were more common
      in patients than in controls. Persistent HPV infection as demonstrated by both
      HPV DNA detection and antibody detection appears to be a risk factor for the
      recurrence of pathological findings in women after surgery. An individually based
      approach to surgical treatment is an important factor in the outcome of disease
      at follow-up.

PMID- 16896829
TI  - Evaluation of serum C-reactive protein, procalcitonin, tumor necrosis factor
      alpha, and interleukin-10 levels as diagnostic and prognostic parameters in
      patients with community-acquired sepsis, severe sepsis, and septic shock.
AB  - The diagnostic value of procalcitonin, C-reactive protein, tumor necrosis factor
      alpha, and interleukin-10 levels in differentiating sepsis from severe sepsis and
      the prognostic value of these levels in predicting outcome were evaluated and
      compared in patients with community-acquired sepsis, severe sepsis, and septic
      shock in the first 72 h of admission to the hospital. Thirty-nine patients were
      included in the study. The severe sepsis and septic shock cases were combined in
      a single "severe sepsis" group, and all comparisons were made between the sepsis
      (n=21 patients) and the severe sepsis (n=18 patients) groups. Procalcitonin
      levels in the severe sepsis group were found to be significantly higher at all
      times of measurements within the first 72 h and were significantly higher at the
      72nd hour in patients who died. Procalcitonin levels that remain elevated at the
      72nd hour indicated a poor prognosis. C-reactive protein levels were not
      significantly different between the groups, nor were they indicative of
      prognosis. No significant differences in the levels of tumor necrosis factor
      alpha were found between the sepsis and severe sepsis groups; however, levels
      were higher at the early stages (at admission and the 24th hour) in patients who
      died. Interleukin-10 levels were also higher in the severe sepsis group and
      significantly higher at all times of measurement in patients who died. When the
      diagnostic and prognostic values at admission were evaluated, procalcitonin and
      interleukin-10 levels were useful in discriminating between sepsis and severe
      sepsis, whereas tumor necrosis factor-alpha and interleukin-10 levels were useful
      in predicting which cases were likely to have a fatal outcome.

PMID- 16896830
TI  - Preoperative risk analysis--a reliable predictor of postoperative outcome after
      transthoracic esophagectomy?
AB  - BACKGROUND AND AIMS: In patients with esophageal carcinoma, transthoracic
      esophagectomy is associated with high postoperative morbidity and mortality
      rates. The question of this study was whether an individualized preoperative risk
      analysis is able to predict postoperative outcome. MATERIALS AND METHODS: Based
      on prospectively accumulated data of 126 patients with a malignant esophageal
      tumor, a preoperative composite risk score using objective parameters was
      evaluated. All patients underwent a transthoracic en bloc esophagectomy with two
      field lymphadenectomy. The risk score was correlated to the postoperative course
      which was classified according to the days of intensive care unit (ICU)
      treatment, hours of mechanical ventilation, and reoperation and readmission to
      the ICU. A multivariate analysis was performed to identify single risk factors.
      RESULTS: The overall morbidity rate was 55%, while the mortality rate was 5.6%.
      According to the composite risk score, 22.8% of the patients had a "low" risk,
      53.2% had a "moderate" risk, and in 19% the preoperative risk was classified as
      "high". There was a significant correlation of the preoperative risk and the
      postoperative course (p<0.001). Multivariate analysis identified age, general
      status, and preoperative pulmonary function as independent risk factors of the
      postoperative outcome. CONCLUSION: Preoperative risk analysis in particular
      pulmonary function and general status helps to select patients for transthoracic
      esophagectomy to reduce postoperative morbidity.

PMID- 16896832
TI  - Identification of three new bovine T-cell receptor delta variable gene subgroups
      expressed by peripheral blood T cells.
AB  - To understand the biology of gammadelta T cells in ruminants, it is necessary to
      have a comprehensive picture of gammadelta T-cell receptor gene diversity and
      expression. In this study, three new subgroups of bovine T-cell receptor delta
      (TRD) variable genes were identified by RT-PCR and sequencing and homology with
      TRDV genes from other mammals determined. Previously unidentified TRDV subgroup
      genes described in this study include the bovine homologues of ovine TRDV2,
      TRDV3, and TRDV4 which were named accordingly. TRDV2 subgroup has two genes
      (TRDV2-1 and TRDV2-2) while we found the previously identified TRDV1 has at least
      eight genes corresponding to separate genomic sequences. Nucleotide and amino
      acid sequences for particular gene subgroups between cattle and sheep were more
      than 87% identical but identities among TRDV subgroups within a species were much
      less, with bovine TRDV4 having <45% identity to the other three bovine TRDV gene
      subgroups. Analysis of circulating bovine gammadelta T cells revealed that genes
      from all four TRDV subgroups were expressed in combination with TRDJ1, TRDJ3, and
      TRDC, although TRDV4 was the least represented, and all displayed a variety of
      CDR3 junctional lengths. Finally, some genes within the TRDV1, TRDV2, and TRDV3
      subgroups recombined with TRAV incorporating TRAJs, suggesting dual use.

PMID- 16896831
TI  - Genomic view of the evolution of the complement system.
AB  - The recent accumulation of genomic information of many representative animals has
      made it possible to trace the evolution of the complement system based on the
      presence or absence of each complement gene in the analyzed genomes. Genome
      information from a few mammals, chicken, clawed frog, a few bony fish, sea
      squirt, fruit fly, nematoda and sea anemone indicate that bony fish and higher
      vertebrates share practically the same set of complement genes. This suggests
      that most of the gene duplications that played an essential role in establishing
      the mammalian complement system had occurred by the time of the teleost/mammalian
      divergence around 500 million years ago (MYA). Members of most complement gene
      families are also present in ascidians, although they do not show a one-to-one
      correspondence to their counterparts in higher vertebrates, indicating that the
      gene duplications of each gene family occurred independently in vertebrates and
      ascidians. The C3 and factor B genes, but probably not the other complement
      genes, are present in the genome of the cnidaria and some protostomes, indicating
      that the origin of the central part of the complement system was established more
      than 1,000 MYA.

PMID- 16896833
TI  - In vitro cleaning efficacy and resistance to insertion test of interdental
      brushes.
AB  - The aim of this study was to compare the resistance to insertion forces and
      cleaning efficacy values of triangular interdental brushes (TIB) and conventional
      round interdental brushes (RIB). Extracted human teeth were fixed in a socket and
      matched to pairs simulating interdental spaces. Before and after standardized
      cleaning of the proximal surfaces, the pre- and postbrushing situations were
      registered with a digital camera. The cleaning efficacy was quantified by digital
      image subtraction. The forces necessary for insertion were measured with a load
      cell. The ratio between the relative cleaning efficacy and the forces necessary
      for insertion was calculated. The results of our study revealed that the relative
      cleaning efficacies of round and TIB were equal. There were no statistically
      significant differences. TIB showed significantly lower resistance to insertion
      values. Consequently, at identical resistance to insertion the TIB cleaned more
      effectively compared with the RIB, which means that the same effectiveness was
      reached by significantly lower forces at insertion. TIB showed a more favorable
      ratio between relative cleaning efficacy and resistance to insertion than RIB.

PMID- 16896834
TI  - Multivariate multilevel models for repeated measures in the study of smoking
      effects on the association between plaque and gingival bleeding.
AB  - Multivariate multilevel modeling was applied to analyze repeated measures data on
      the influence of heavy smoking on the association between the amount of
      supragingival plaque and gingival bleeding on probing (BOP) in a steady-state
      plaque environment. Data acquired in 65 systemically healthy young adults with
      mild plaque-induced gingivitis were analyzed. 33 heavy smokers consumed at least
      20 cigarettes per day while 32 were non-smokers. Periodontal examinations at the
      outset consisted of periodontal probing depth, clinical attachment level, BOP,
      plaque index, and presence of calculus at 6 sites of every tooth present. They
      were repeated 3 times every 8 weeks. A multivariate 4-level variance component
      model revealed that the odds of BOP was twice as high in smokers. In addition,
      females had a lower likelihood for BOP but, with increasing bleeding scores
      during the course of the study, this effect attenuated. Low biserial correlations
      for BOP at the site level of between 0.11 and 0.2 were found. At the tooth level,
      correlations were moderate (0.2-0.5), and highest at the subject level (0.8-0.9).
      Variations at subject and tooth levels were very large at the outset but notably
      attenuated in the course of the study. Plaque consistently influenced the
      tendency for BOP with an odds ratio of about 1.7-1.8 for each increase in score
      in both smokers and non-smokers. The present study did not reveal evidence for
      attenuation of the plaque/gingival bleeding relationship in heavy smokers.

PMID- 16896835
TI  - Clinical features of incontinentia pigmenti with emphasis on oral and dental
      abnormalities.
AB  - One of interesting aspects in dermatology is the fact that skin may reflect the
      presence of anomalies in other organs and tissues. One such example is
      incontinentia pigmenti (IP), a rare, complex, X-linked genodermatosis. Clinical
      manifestations of IP according to evolution and prognosis can be considered as
      skin, as well as dental, eye, and central nervous system, changes. We have
      investigated a total of nine families with 25 subjects, 23 females and 2 males.
      In 12 female and 2 male subjects, all of them with clinical characteristics of
      IP, we observed the following abnormalities: teeth-shape anomalies (coni- or peg
      like teeth), the presence of numerous cariotic teeth, early dental loss, delayed
      eruption, partial anodontia, and gothic palate. To our knowledge, this is the
      first time that the presence of gothic palate in patients with IP has been
      documented. As we found out, in two female subjects and one male subject, in
      which nonrandomed X inactivation did not occur, gothic palate could be supposed
      as characteristic of IP.

PMID- 16896836
TI  - Effect of meloxicam on gingival crevicular fluid IL-1beta and IL1 receptor
      antagonist levels in subjects with chronic periodontitis, and its effects on
      clinical parameters.
AB  - The aim of the present study was to determine the effects of meloxicam after
      initial periodontal treatment on interleukin-1beta (IL-1beta) and IL-1 receptor
      antagonist (IL-1ra) in gingival crevicular fluid (GCF) and clinical parameters in
      the chronic periodontitis patients. Data were obtained from 30 patients with
      chronic periodontitis. Fifteen chronic periodontitis patients received 7.5 mg
      meloxicam, and 15 patients received placebo tablets in a 1x1 regimen for 1 month.
      All subjects were nonsmokers and had not received any periodontal therapy. The
      plaque index (PI), gingival index (GI), probing depth (PD), and clinical
      attachment level (CAL) were recorded. The GCF was collected using a paper strip:
      eluted and enzyme-linked immunoabsorbent assays (ELISAs) were performed to
      determine the cytokine levels. The clinical data and GCF samples were obtained
      after periodontal therapy and 1 month after periodontal therapy. The PI, GI, PD,
      and GCF IL-1ra decreased significantly (p<0.05) in meloxicam group at first month
      when comparing the initial levels. While decrease of the PI was statistically
      significant in control group (p<0.05), statistically significant changes were not
      determined in the other clinical parameters and GCF cytokine levels (p>0.05).
      There were no significant differences between two groups in any of the
      investigated parameters. Our observations did not reveal any influence of
      meloxicam on levels of IL-1beta and IL-1ra in chronic periodontitis. Additional
      clinical studies are advisable to determine whether COX-2 selective drugs alter
      periodontal disease outcome with greater safety.

PMID- 16896837
TI  - Influence of the methodology and evaluation criteria on determining microleakage
      in dentin-restorative interfaces.
AB  - This in vitro study compared microleakage along the dentin-restorative interface
      using a spectrophotometer protocol and two conventional single-surface methods
      (scores and percentages), using an organic dye (0.5% buffered methylene blue) or
      a tracer (50% silver nitrate). Occluso-proximal preparations with gingival
      margins in dentin were made in 40 human teeth. The teeth were divided into four
      groups (n=10) according to the solution dyes and adhesive system used: group 1,
      single bond/methylene blue; group 2, single bond/silver nitrate; group 3,
      Clearfil SE Bond/methylene blue; and group 4, Clearfil SE Bond/silver nitrate.
      The dye penetration measurements were made in all groups, using scores and
      percentages. Groups 1 and 3 were also assessed by UV spectrophotometer. For
      percentage measurement, the data were submitted to ANOVA and Tukey's test. For
      the material factor, there was a statistically significant difference between
      groups 1 and 3. For the dye factor, there was a statistically significant
      difference between groups 3 and 4. The score results were submitted to Kruskall
      Wallis test and showed differences between groups 1 and 3 and groups 2 and 3. For
      spectrophotometer measurement, no significant difference was observed between
      groups 1 and 3. The results of dye penetration suggest that there was a
      difference between dyes and measurement methods, and this should change the
      interpretation of microleakage tests.

PMID- 16896838
TI  - Modic changes and their associations with clinical findings.
AB  - It is believed that disc degeneration (DD) is, in general, only mildly associated
      with low back pain (LBP). MRI-identified Modic changes (MC), probably a late
      stage of DD, are relatively strongly associated with LBP but it is not known if
      people with MC also have a specific clinical profile. The purpose of this study
      was to investigate if the clinical findings differ in people with Modic changes
      (MC) as compared to those with only degenerative disc findings or none at all. In
      a population-based sample of 412 40-year-old Danes, information was collected
      independently with MRI, questionnaires and clinical examination. Three subgroups
      of people were created: those with both DD and MC, those with only DD, and those
      with neither DD nor MC. The clinical pattern was investigated for each subgroup
      in order to test the assumption that the clinical picture differs in the three
      groups. It was expected that people with both DD and MC would have a more
      pronounced clinical profile than those with only DD who, in turn, would differ
      from those with neither of these two MRI findings. Our findings were generally in
      concordance with our expectations. MC constitutes the crucial element in the
      degenerative process around the disc in relation to LBP, history, and clinical
      findings. People with DD and no MC only vaguely differ from those without. People
      with LBP and MC may deserve to be diagnosed as having specific LBP.

PMID- 16896839
TI  - Bilateral pedicle stress fracture in the lumbar spine of a sedentary office
      worker.
AB  - A case of bilateral pedicle fracture in the lumbar spine of a sedentary office
      worker is being presented. No such case has been reported in the literature
      previously. Bilateral pedicle fracture is a rare entity. Few cases have been
      reported in literature. All the reported cases had some underlying causative
      factors like degenerative spine disease, previous spinal surgery or stress
      related activities, e.g. athletes. Our case is a 36-year-old sedentary office
      worker with none of the factors mentioned. We present a case of a 36-year-old
      sedentary worker with long-standing low backache. There were no root tension
      signs. Plain radiographs were inconclusive. The patient had a CT scan. The CT
      scan revealed long-standing defects in the pedicles of L2 vertebra with
      pseudoarthrosis. Infiltration with anaesthetic relieved the symptoms. Our patient
      was managed conservatively with spine rehabilitation physiotherapy program.
      Pedicle fracture can develop due to abnormal stresses in the pedicle either
      because of previous spinal surgery or spondylitic changes in the spine. Bilateral
      pedicle fracture in the absence of these conditions is extremely rare.

PMID- 16896840
TI  - Electromyographic activity of trunk and hip muscles during stabilization
      exercises in four-point kneeling in healthy volunteers.
AB  - Stabilization exercises are intended to optimize function of the muscles that are
      believed to govern trunk stability. Debate exists whether certain muscles are
      more important than others in optimally performing these exercises. Thirty
      healthy volunteers were asked to perform three frequently prescribed
      stabilization exercises in four-point kneeling. The electromyographic activity of
      different trunk and hip muscles was evaluated. Average amplitudes obtained during
      the exercises were normalized to the amplitude in maximal voluntary contraction
      (% MVIC). During all three exercises, the highest relative muscle activity levels
      (> 20% MVIC) were consistently found in the ipsilateral lumbar multifidus and
      gluteus maximus. During both the single leg extension (exercise 1) and the leg
      and arm extension exercise (exercise 2) the contralateral internal oblique and
      ipsilateral external oblique reached high levels (> 20%MVIC). During exercise 2
      there were also high relative activity levels of the ipsilateral lumbar part and
      the contralateral thoracic part of the iliocostalis lumborum and the
      contralateral lumbar multifidus. During the leg and arm extension exercise with
      contralateral hip flexion (exercise 3) there were high relative muscle activity
      levels of all back muscles, except for the latissimus dorsi muscle. The lowest
      relative muscle activity levels (< 10% MVIC) were found in the rectus abdominis
      and the ipsilateral internal oblique during all exercises, and in the
      contralateral gluteus maximus during exercises 1 and 2. The results of this study
      show that in exercises in four-point kneeling performed by healthy subjects, hip
      and trunk muscles seem to work together in a harmonious way. This shows that when
      relative activity of muscles is measured, both "global and local" muscles
      function together in order to stabilize the spine.

PMID- 16896841
TI  - Vascular complications of prosthetic inter-vertebral discs.
AB  - Five consecutive cases of prosthetic inter-vertebral disc displacement with
      severe vascular complications on revisional surgery are described. The objective
      of this case report is to warn spinal surgeons that major vascular complications
      are likely with anterior displacement of inter-vertebral discs. We have not been
      able to find a previous report on vascular complications associated with anterior
      displacement of prosthetic inter-vertebral discs. In all five patients the
      prosthetic disc had eroded into the bifurcation of the inferior vena cava and the
      left common iliac vein. In three cases the aortic bifurcation was also involved.
      The fibrosis was so severe that dissecting out the arteries and veins to provide
      access to the relevant disc proved impossible. Formal division of the left common
      iliac vein and artery with subsequent repair was our solution. Anterior inter
      vertebral disc displacement was associated with severe vascular injury.
      Preventing anterior disc displacement is essential in disc design. In the event
      of anterior displacement, disc removal should be planned with a Vascular Surgeon.

PMID- 16896842
TI  - Auto fluorescence of intervertebral disc tissue: a new diagnostic tool.
AB  - The paper reports on auto fluorescence phenomena of inter-vertebral human discs.
      It systematically investigates the auto fluorescence effects of ex vivo disc
      specimen and reports on surgical cases to demonstrate the potential value of the
      new method. The paper offers biologic explanations of the phenomenon and
      discusses the potential value of the UV auto fluorescence technique as a
      diagnostic tool. Intra- and postoperative observations are made by a surgical
      microscope with an integrated UV light source. Quantitative measurements were
      carried out using a photon counter and a spectrometer ex vivo. The auto
      fluorescence phenomenon allows the differentiation of traumatized and degenerated
      disc tissue intraoperatively in some cases, it allows the differentiation of bony
      and collagen endplate in cervical disc surgery. The source of the auto
      fluorescent light emission are amino acids of the collagen molecules. The
      proteoglycan components and the liquid components of the disc do not show
      relevant auto fluorescence. Emission wavelength of disc material is equivalent to
      color perception. It differs due to different collagen composition of the
      intervertebral disc components from yellow-green to blue-green and can be
      visualized in situ by naked eye.UV-auto fluorescence of inter-vertebral discs is
      a new clinical tool that has the potential to differentiate disc material from
      the anatomical surrounding, to distinguish between different fractions of the
      disc and to give information on the quality and status of the disc material.
      Since the technology has just emerged, it needs further investigations to
      quantify the clinical observations reported in this paper.

PMID- 16896845
TI  - Remembrance of weaning past: the seminal papers.
AB  - The approach to ventilator weaning has changed considerably over the past 30
      years. Change has resulted from research in three areas: pathophysiology, weaning
      predictor testing, and weaning techniques. Physiology research illuminated the
      mechanisms of weaning failure. It also uncovered markers of weaning success.
      Through more reliable prediction, patients whose weaning would have been tedious
      in the 1970s are now weaned more rapidly. The weaning story offers several
      lessons in metascience: importance of creativity, the asking of heretical
      questions, serendipity, mental-set psychology, cross-fertilization, and the
      hazards of precocity. Weaning research also illustrates how Kuhnian normal (me
      too) science dominates any field. Making the next quantum leap in weaning will
      depend on spending less time on normal science and more on the raising (and
      testing) of maverick ideas.

PMID- 16896846
TI  - Relation between PaO2/FIO2 ratio and FIO2: a mathematical description.

PMID- 16896847
TI  - The effect of an algorithm-based sedation guideline on the duration of mechanical
      ventilation in an Australian intensive care unit.
AB  - OBJECTIVE: To examine the effect of an algorithm-based sedation guideline
      developed in a North American intensive care unit (ICU) on the duration of
      mechanical ventilation of patients in an Australian ICU. DESIGN AND SETTING: The
      intervention was tested in a pre-intervention, post-intervention comparative
      investigation in a 14-bed adult intensive care unit. PATIENTS: Adult mechanically
      ventilated patients were selected consecutively (n=322). The pre-intervention and
      post-intervention groups were similar except for a higher number of patients with
      a neurological diagnosis in the pre-intervention group. INTERVENTION: An
      algorithm-based sedation guideline including a sedation scale was introduced
      using a multifaceted implementation strategy. MEASUREMENTS AND RESULTS: The
      median duration of ventilation was 5.6 days in the post-intervention group,
      compared with 4.8 days for the pre-intervention group (P=0.99). The length of
      stay was 8.2 days in the post-intervention group versus 7.1 days in the pre
      intervention group (P=0.04). There were no statistically significant differences
      for the other secondary outcomes, including the score on the Experience of
      Treatment in ICU 7 item questionnaire, number of tracheostomies and number of
      self-extubations. Records of compliance to recording the sedation score during
      both phases revealed that patients were slightly more deeply sedated when the
      guideline was used. CONCLUSIONS: The use of the algorithm-based sedation
      guideline did not reduce duration of mechanical ventilation in the setting of
      this study.

PMID- 16896848
TI  - Incidence, risk factors and prognosis of changes in serum creatinine early after
      aortic abdominal surgery.
AB  - OBJECTIVE: To determine the incidence, risk factors, and prognostic implications
      of serum creatinine changes following major vascular surgery. DESIGN:
      Observational study. SETTINGS: University hospital. PATIENTS: Cohort of 599
      consecutive patients undergoing elective abdominal aortic surgery. INTERVENTIONS:
      Review of prospectively collected data from 1993 to 2004. MEASUREMENTS AND
      RESULTS: The receiver-operator characteristic (ROC) curve analysis was used to
      detect the best threshold for postoperative elevation in serum creatinine (Delta
      Creat) in relation to major complications. A cut-off value of +0.5 mg/dl was
      selected to define renal dysfunction (RD(0.5) group, n=91; no RD(0.5), n=508)
      that was associated with higher mortality (7.7% in RD(0.5) group vs 1.4% in no
      RD(0.5) group, P<0.05), rate of admission to the ICU (34% vs 13%, P<0.05), and
      incidence of cardiovascular (9% vs 4%, P<0.05), respiratory (21% vs 7%, P<0.05),
      surgical (24% vs 10%, P<0.05), and septic complications (9% vs 3%, P<0.05). After
      multivariate analysis with logistic regression, renal dysfunction was
      independently related to low preoperative creatinine clearance [<40 ml/min; odds
      ratio (OR) 1.5, 95% confidence interval (CI) 1.1-3.9], prolonged renal ischemic
      time (>40 min; OR, 3.8, 95% CI, 1.9-7.2), blood transfusion (>5 units; OR, 1.9,
      95% CI 1.2-6.1), and rhabdomyolysis (OR, 3.6, 95% CI 1.7-7.9). CONCLUSIONS:
      Postoperative RD(0.5) (Delta Creat >0.5 mg/dl) occurs in 15% of vascular patients
      and carries a bad prognosis. Preoperative renal insufficiency and factors related
      to the complexity of surgery are the main predictors of renal dysfunction.

PMID- 16896849
TI  - Predictors of early recovery of health status after intensive care.
AB  - OBJECTIVE: To identify factors predictive of good or poor recovery of health
      status and health-related quality of life (HRQOL) 90 days after admission to an
      intensive care unit (ICU). DESIGN AND SETTING: Prospective international
      multicentre study in 19 ICUs participating in the HRQOL substudy of the SAPS 3
      project. INTERVENTION: The EuroQol questionnaire (EQ) was administered to
      discharged ICU patients 90 days after admission. A question to compare present
      health status with that 3 months before ICU admission (same/better/worse) was
      added. PATIENTS: Six hundred and eighteen patients who spent >24h in an ICU and
      survived for 90 days. EQ data and health comparison were available in 559 (90.5%)
      of them. MEASUREMENTS AND RESULTS: Patients reported their general level of
      health to be better (33.8%), the same (31.1%), or worse (35.1%) in comparison
      with baseline. Recovery was considered to be good for answers "better" or "the
      same". Regression analysis showed that transplantation surgery [odds ratio (OR)
      0.07, 95% confidence interval (CI) 0.01-0.63], coronary artery bypass surgery
      without valvular repair (OR 0.39, 95% CI 0.17-0.92) and being admitted to the ICU
      from a ward or other location (OR 0.55, 95% CI 0.31-0.95) predicted good recovery
      of health. Predictors of poor recovery (all present at the time of ICU admission)
      were unplanned ICU admission, hypothermia, serum creatinine level >or=2mg/dl,
      pH<or=7.25 and metastatic cancer. CONCLUSIONS: More than 60% of ICU patients
      report good recovery of their health 90 days after ICU admission, depending on
      their illness and circumstances of ICU admission.

PMID- 16896850
TI  - Serum procalcitonin measurement contribution to the early diagnosis of candidemia
      in critically ill patients.
AB  - BACKGROUND: Candidemia is a life-threatening infection in the ICU whose prognosis
      is highly dependent on the stage at which it is recognized. Procalcitonin (PCT)
      levels have been shown to accurately distinguish between bacteremia and
      noninfectious inflammatory states in critically ill patients with clinical signs
      of sepsis. Little is known about the accuracy of PCT for the diagnosis of
      candidemia in this setting. SETTING: A medical intensive care unit in a teaching
      hospital. PATIENTS AND METHODS: Review of the medical records of every non
      neutropenic patient with either bacteremia or candidemia and clinical sepsis in
      whom PCT dosage at the onset of infection was available between May 2004 and
      December 2005. RESULTS: Fifty episodes of either bacteremia (n=35) or candidemia
      (n=15) were included. PCT levels were found to be markedly higher in patients
      with bacteremia than in those with candidemia. Moreover, a low PCT value was
      found to be an independent predictor of candidemia in the study population.
      According to the calculation of the area under the receiver operating
      characteristic curve, PCT was found to be accurate in distinguishing between
      candidemia and bacteremia (0.96 [0.03]). A PCT level of higher than 5.5 ng/ml
      yields a 100% negative predictive value and a 65.2% positive predictive value for
      candidemia-related sepsis. CONCLUSION: A high PCT value in a critically ill non
      neutropenic patient with clinical sepsis is unlikely in the setting of
      candidemia.

PMID- 16896851
TI  - Ethics and research in critical care.
AB  - BACKGROUND: The past few years have witnessed several controversies regarding the
      ethics of conducting research involving critically ill patients, and such
      research is ethically challenging. DISCUSSION: Research ethics is a changing
      field, one that is influenced by empirical data, contemporary events, and new
      ideas regarding aspects of clinical trial design and protection of human
      subjects. We describe recent thoughts regarding several aspects of research
      ethics in the critical care context. CONCLUSION: The ability of the research
      community to conduct research ethically and to maintain public trust would
      benefit from heightened awareness to the principles and requirements that govern
      such research.

PMID- 16896853
TI  - Abdominal compartment syndrome: it's time to pay attention!

PMID- 16896852
TI  - Effects of long-term routine use of selective digestive decontamination on
      antimicrobial resistance.
AB  - OBJECTIVE: To assess the distribution of bacterial species and antimicrobial
      resistance in an ICU during long-term use of selective digestive decontamination
      (SDD) in the context of national reference data. DESIGN AND SETTING: Five-year
      prospective observational study in a 24-bed interdisciplinary surgical ICU of a
      university hospital (study ICU) participating in the project "Surveillance of
      Antimicrobial Use and Antimicrobial Resistance in German Intensive Care Units"
      (SARI; reference ICUs). PATIENTS: Resistance data were obtained from all
      patients; patients intubated for at least 2 days received SDD (colistin,
      tobramycin, amphotericin B). INTERVENTIONS AND MEASUREMENTS: SDD was performed in
      1,913 of 7,270 patients. Antimicrobial resistance was examined in 4,597 (study
      ICU) and 46,346 (reference ICUs) isolates. RESULTS: Methicillin-resistant
      Staphylococcus aureus (MRSA) remained stable (2.76 and 2.58 isolates/1000 patient
      days) in the study ICU; this was below the German average (4.26 isolates/1000
      patient days). Aminoglycoside- and betalactam-resistant Gram-negative rods did
      not increase during SDD use. Aminoglycoside resistance of Pseudomonas aeruginosa
      was 50% below the mean value of SARI (0.24 vs. 0.52 isolates/1,000 patient days).
      The relative frequency of enterococci and coagulase-negative staphylococci (CNS)
      was higher than in the SARI ICUs (23.2% vs. 17.3%, and 25.0% vs. 20.6%,
      respectively). CONCLUSION: Routine 5-year-use of SDD was not associated with
      increased antimicrobial resistance in our ICU with low baseline resistance rates.
      Vigorous surveillance and control measures to search and destroy MRSA were
      considered a mandatory component of the SDD program. The relative increase in
      enterococci and CNS is of concern requiring further investigation.

PMID- 16896855
TI  - Diverse outcome after air embolism in nonventilated preterm infants.

PMID- 16896854
TI  - Patient-ventilator asynchrony during assisted mechanical ventilation.
AB  - OBJECTIVE: The incidence, pathophysiology, and consequences of patient-ventilator
      asynchrony are poorly known. We assessed the incidence of patient-ventilator
      asynchrony during assisted mechanical ventilation and we identified associated
      factors. METHODS: Sixty-two consecutive patients requiring mechanical ventilation
      for more than 24 h were included prospectively as soon as they triggered all
      ventilator breaths: assist-control ventilation (ACV) in 11 and pressure-support
      ventilation (PSV) in 51. MEASUREMENTS: Gross asynchrony detected visually on 30
      min recordings of flow and airway pressure was quantified using an asynchrony
      index. RESULTS: Fifteen patients (24%) had an asynchrony index greater than 10%
      of respiratory efforts. Ineffective triggering and double-triggering were the two
      main asynchrony patterns. Asynchrony existed during both ACV and PSV, with a
      median number of episodes per patient of 72 (range 13-215) vs. 16 (4-47) in 30
      min, respectively (p=0.04). Double-triggering was more common during ACV than
      during PSV, but no difference was found for ineffective triggering. Ineffective
      triggering was associated with a less sensitive inspiratory trigger, higher level
      of pressure support (15 cmH(2)O, IQR 12-16, vs. 17.5, IQR 16-20), higher tidal
      volume, and higher pH. A high incidence of asynchrony was also associated with a
      longer duration of mechanical ventilation (7.5 days, IQR 3-20, vs. 25.5, IQR 9.5
      42.5). CONCLUSIONS: One-fourth of patients exhibit a high incidence of asynchrony
      during assisted ventilation. Such a high incidence is associated with a prolonged
      duration of mechanical ventilation. Patients with frequent ineffective triggering
      may receive excessive levels of ventilatory support.

PMID- 16896856
TI  - Effects of vertical positioning on gas exchange and lung volumes in acute
      respiratory distress syndrome.
AB  - OBJECTIVE: Supine position may contribute to the loss of aerated lung volume in
      patients with acute respiratory distress syndrome (ARDS). We hypothesized that
      verticalization increases lung volume and improves gas exchange by reducing the
      pressure surrounding lung bases. DESIGN AND SETTING: Prospective observational
      physiological study in a medical ICU. SUBJECTS AND INTERVENTION: In 16 patients
      with ARDS we measured arterial blood gases, pressure-volume curves of the
      respiratory system recorded from positive-end expiratory pressure (PEEP), and
      changes in lung volume in supine and vertical positions (trunk elevated at 45
      degrees and legs down at 45 degrees ). MEASUREMENTS AND RESULTS: Vertical
      positioning increased PaO(2) significantly from 94+/-33 to 142+/-49 mmHg, with an
      increase higher than 40% in 11 responders. The volume at 20 cmH(2)O measured on
      the PV curve from PEEP increased using the vertical position only in responders
      (233+/-146 vs. -8+/-9 1ml in nonresponders); this change was correlated to
      oxygenation change (rho=0.55). End-expiratory lung volume variation from supine
      to vertical and 1 h later back to supine, measured in 12 patients showed a
      significant increase during the 1-h upright period in responders (n=7) but not in
      nonresponders (n=5; 215+/-220 vs. 10+/-22 ml), suggesting a time-dependent
      recruitment. CONCLUSIONS: Vertical positioning is a simple technique that may
      improve oxygenation and lung recruitment in ARDS patients.

PMID- 16896857
TI  - Adrenal insufficiency in severe West Nile Virus infection.
AB  - OBJECTIVE: To explore adrenal function in severe West Nile virus (WNV) infection.
      DESIGN AND SETTING: Prospective interventional cohort study in a medical ICU of a
      teaching hospital. PATIENTS: Ten consecutive patients (seven men, mean age 64+/
      12years, mean SAPS II 26+/-6) with definite diagnosis of WNV related
      meningoencephalitis and variable proportion of organ/system failure. All patients
      had fever (mean body temperature 39+/-1 degrees C) and altered mental status
      (mean Glasgow Coma Score 11+/-2). Mean SOFA score was 9+/-2; eight patients had
      systemic inflammatory response syndrome, five septic shock, and six acute
      respiratory failure (usually from central origin) requiring mechanical
      ventilation. INTERVENTIONS: A short corticotropin test was performed in each
      patient to assess the adrenal function. MEASUREMENTS AND RESULTS: Cortisol
      response was defined as the difference between baseline and corticotropin
      stimulated peak. Absolute adrenal insufficiency was defined by a baseline
      cortisol level below 15 microg/dl (415 nmol/l). Relative insufficiency was
      defined by a cortisol response of 9 microg/dl (250 nmol/l) or less. Relative
      adrenal insufficiency, defined by a corticotropin response below 9 microg/dl, was
      observed in seven while the remaining three had normal cortisol response; six out
      of these seven died in the ICU. All patients with normal adrenal function
      survived. CONCLUSION: Adrenal insufficiency is frequent in severe WNV infection
      and carries a poor outcome. In the absence of specific effective treatment, our
      data provide a rational to investigate a supplemental corticosteroid treatment in
      a controlled trial.

PMID- 16896858
TI  - Lund Therapy - pathophysiology-based therapy or contrived over-interpretation of
      limited data?

PMID- 16896860
TI  - Life-support limitation in the pre-hospital setting.

PMID- 16896859
TI  - The "Lund Concept" for the treatment of severe head trauma--physiological
      principles and clinical application.
AB  - The Lund Concept is an approach to the treatment of severe brain trauma that is
      mainly based on hypotheses originating from basic physiological principles
      regarding brain volume and cerebral perfusion regulation. Its main attributes
      have found support in experimental and clinical studies. This review explains the
      principles of the Lund Concept and is intended to serve as the current guide for
      its clinical application. The therapy has two main goals: (1) to reduce or
      prevent an increase in ICP (ICP-targeted goal) and (2) to improve perfusion and
      oxygenation around contusions (perfusion-targeted goal). The Lund therapy
      considers the consequences of a disrupted blood-brain barrier for development of
      brain oedema and the specific consequences of a rigid dura/cranium for general
      cerebral haemodynamics. It calls attention to the importance of improving
      perfusion and oxygenation of the injured areas of the brain. This is achieved by
      normal blood oxygenation, by maintaining normovolaemia with normal haematocrit
      and plasma protein concentrations, and by antagonizing vasoconstriction through
      reduction of catecholamine concentration in plasma and sympathetic discharge
      (minimizing stress and by refraining from vasoconstrictors and active cooling).
      The therapeutic measures mean normalization of all essential haemodynamic
      parameters (blood pressure, plasma oncotic pressure, plasma and erythrocyte
      volumes, PaO(2), PaCO(2)) the use of enteral nutrition, and avoidance of
      overnutrition. To date, clinical outcome studies using the Lund Concept have
      shown favourable results.

PMID- 16896861
TI  - Prehospital withholding and withdrawal of life-sustaining treatments. The French
      LATASAMU survey.
AB  - OBJECTIVE: To investigate the end-of-life decision process in patients managed by
      emergency physicians in the prehospital setting. DESIGN: A 40-item retrospective
      study about most recent end-of-life decision in the prehospital setting. PATIENTS
      AND PARTICIPANTS: 1069 physicians (44.9%) from 192 French emergency mobile units.
      MEASUREMENTS AND RESULTS: A total of 816 (76.3%) physicians reported at least one
      prehospital end-of-life decision. Conscious patients were involved in 30.7%
      (54/176) and families in 63.6% of cases. The physician discussed the end-of-life
      decision with at least one other physician in 56.5% of cases. Perceived imminent
      death was the most frequently reported criterion (90.1%). Nearly four fifths of
      patients died before arrival at the hospital (78.8%). Factors independently
      associated with prehospital withdrawal decision included multiple trauma [odds
      ratio (OR) 5.7, 95% confidence interval (CI) 1.6-19.7], intubation (OR 3.9, 95%
      CI 2.3-6.5), chronic disease with severe heart failure (OR 2.8, 95% CI 1.5-5.2),
      acute event with postanoxic coma (OR 2.2, 95% CI 1.3-4.0), emergency physician
      from a teaching hospital (OR 2.1, 95% CI, 1.3-3.5), male patient (OR 1.9, 95% CI
      1.1-3.3), and no sedation (OR 1.9, 95% CI 1.2-3.1). Prehospital withholding
      decisions were taken for 684 (88%) patients and withdrawing decisions for 12%.
      CONCLUSIONS: Treatment withholding and withdrawal is common in the prehospital
      setting in France. These decisions remain highly questionable in this emergency
      context, in the absence of knowledge of the patient's medical history and of
      patients' and relatives' clear wishes concerning end-of-life decisions.

PMID- 16896862
TI  - Does helmet CPAP reduce cerebral blood flow and volume by comparison with Infant
      Flow driver CPAP in preterm neonates?
AB  - OBJECTIVE: We compared neonatal helmet continuous positive airway pressure (CPAP)
      and the conventional nasal Infant Flow driver (IFD) CPAP in the noninvasive
      assessment of absolute cerebral blood flow (CBF) and relative cerebral blood
      volume changes (DeltaCBV) by near-infrared spectroscopy. DESIGN AND SETTING: A
      randomized crossover study in a tertiary referral NICU. PATIENTS AND
      INTERVENTIONS: Assessment of CBF and DeltaCBV in 17 very low birth weight infants
      with respiratory distress (median age 5 days) treated with two CPAP devices at a
      continuous distending pressure of 4 mbar. MEASUREMENTS AND RESULTS: Neonates were
      studied for two consecutive 60-min periods with helmet CPAP and with IFD CPAP.
      Basal chromophore traces enabled DeltaCBV changes to be calculated. CBF was
      calculated in milliliters per 100 grams per minute from the saturation rise
      integral and rate of rise O(2)Hb-HHb. Median (range) CBF with helmet CPAP was
      27.37 (9.47-48.20) vs. IFD CBF 34.74 (13.59-60.10)(p=0.049) and DeltaCBV 0.15
      (0.09-0.28) with IFD and 0.13 (0.07-0.27) with helmet CPAP (NS). Using helmet and
      IFD CPAP, the neonates showed no difference in mean physiological parameters
      (transcutaneous carbon dioxide and oxygen tension, pulse oximetry saturation,
      heart rate, breathing rate, mean arterial blood pressure, desaturation rate,
      axillary temperature). CONCLUSION: Assessing CBF and DeltaCBV measured by near
      infrared spectroscopy with two CPAP devices revealed no differences in relative
      blood volume, but CBF was lower with helmet CPAP. Greater active vasoconstriction
      and/or passive capillary and/or venous vessel compression seem the most likely
      reason, due to a positive pressure around the head, neck, and shoulders by
      comparison with the airway pressure.

PMID- 16896863
TI  - Changes in severity and organ failure scores as prognostic factors in onco
      hematological malignancy patients admitted to the ICU.
AB  - OBJECTIVE: To determine whether severity and organ failure scores over the first
      3 days in an ICU predict in-hospital mortality in onco-hematological malignancy
      patients. DESIGN AND SETTING: Retrospective study in a 22-bed medical ICU.
      PATIENTS: 92 consecutive patients with onco-hematological malignancies including
      20 hematopoietic stem cell transplantation (HSCT) patients (11 with allogenic
      HSCT). MEASUREMENTS: Simplified Acute Physiology Score (SAPS) II, Organ
      Dysfunction and/or Infection (ODIN) score, Logistic Organ Dysfunction System
      (LODS), and Sequential Organ Failure Assessment (SOFA) score were recorded on
      admission. The change in each score (Delta score) during the first 3 days in the
      ICU was calculated as follows: severity or organ failure score on day 3 minus
      severity or organ failure score on day 1, divided by severity or organ failure
      score on day 1. RESULTS: In-hospital mortality was 58%. Using multivariate
      analysis in-hospital mortality was predicted by all scores on day 1 and all Delta
      scores. Areas under the receiver operating characteristics curves were similar
      for SAPS II (0.78), ODIN (0.78), LODS (0.83), and SOFA (0.78) scores at day 1.
      They were also similar for DeltaSAPS II, DeltaODIN, DeltaLODS, and DeltaSOFA.
      Similar results were observed when excluding patients with allogenic HSCT.
      CONCLUSION: Severity and three organ failure scores on day 1 and Delta scores
      perform similarly in predicting in-hospital mortality in ICU onco-hematological
      malignancy patients but do not predict individual outcome. Decision to admit such
      patients to the ICU or to forgo life-sustaining therapies should not be based on
      these scores.

PMID- 16896864
TI  - Outcome assessment of bracing in adolescent idiopathic scoliosis by the use of
      the SRS-22 questionnaire.
AB  - The SRS-22 questionnaire is specifically designed for the assessment of quality
      of life in spinal deformity patients. This study is the first to use it to assess
      the quality of life of adolescent idiopathic scoliosis patients under brace
      treatment and compares the results with an observational group matched by age and
      curve magnitude. Forty-six patients were enrolled into each group. Overall, it
      was found that patients under observation had a significantly better quality of
      life than braced patients. Specifically, the domains for function/activity and
      self-image were most affected. This effect was most apparent in those with a
      curve magnitude of under 20 degrees . The scores did not improve significantly
      with the duration of brace wear, suggesting little adaptation. This study has
      implications for treatment, and more attention will need to be given to those
      with mild but progressive curves to help improve patients' understanding of their
      treatment and hence their compliance and satisfaction.

PMID- 16896865
TI  - Minimally invasive Oxford medial unicompartmental knee arthroplasty. A note of
      caution!
AB  - We present the peak outcome results of the Oxford medial unicompartmental
      arthroplasty through a minimally invasive surgical incision. This prospective
      study included 78 Oxford medial unicompartmental knee replacements in 68
      patients. At the 2 year review the patients achieved a mean Oxford Knee Score of
      38.3. This was not significantly different to the 2 year results of the phase 2
      Oxford knee carried out using a standard parapatellar approach when patients
      achieved a mean OKS of 36.0. Four unicompartmental knee replacements required
      revision for unexplained pain, deep infection, aseptic loosening and bearing
      dislocation. Minimally invasive joint replacement is attractive to both patients
      and surgeons, but is technically demanding with complications inherent to limited
      access.

PMID- 16896868
TI  - Misprints in a published paper.

PMID- 16896869
TI  - Lower limb salvage surgery: modular endoprosthesis in bone tumour treatment.
AB  - We retrospectively analysed 90 patients who underwent "en bloc" resection and
      modular endoprosthesis reconstruction in the lower limbs between 1987-2003. After
      proximal femur resection, reconstruction was performed with a modular
      endoprosthesis by Howmedica (KFTR, designed by Kotz) and modular revision
      endoprosthesis by W. Link or Lima-Lto (Revision system, designed by Wagner). The
      knee joint was reconstructed with a modular endoprosthesis (Howmedica, KFTR
      designed by Kotz) after distal femur or proximal tibia resection. Malignant bone
      tumours were present in 58 patients (64.5%), benign tumours in 16 (17.8%),
      metastases in 8 (8.9%), tumour-like lesions in 4 (4.4 %) and non-tumour-related
      destruction of the femur in 4 patients (4.4%). High-grade tumours were found in
      the majority of malignant bone tumours (70.7%). Treatment complications, which
      occurred in 26 patients, were: local recurrence of the tumour, deep infection,
      acetabular destruction following hemiarthroplasty, recurrent dislocations of
      endoprosthesis, periprosthetic fracture and hardware problems. In total, 23
      patients (25.6%) died due to tumours. Endoprostheses should be considered as a
      treatment of choice for bone tumours in the hip and knee joint region. Advances
      in limb salvage surgery are, and will long continue to be, a great challenge for
      orthopaedic oncologists of the 21st century.

PMID- 16896870
TI  - Current strategies of chemotherapy in osteosarcoma.
AB  - Osteosarcoma, the most common type of primary malignant tumour that develops in
      bone, can be classified into several different sub-types. While the majority of
      osteosarcomas are highly malignant, there are some low-grade variants. Since the
      introduction of chemotherapy into the multi-modal treatment regimen of high-grade
      osteosarcoma, its prognosis has impressively improved, with long-term survival
      being achieved in two-thirds of all patients. This review summarises current
      chemotherapeutic treatment strategies in classical osteosarcoma and also
      addresses the indication for chemotherapy in more unusual types and variants. It
      emphasises the need for treatment in specialised centres and within prospective,
      multi-institutional trials, amongst which EURAMOS1 and EURO-B.O.S.S are currently
      active in many European countries.

PMID- 16896871
TI  - Unicompartmental versus computer-assisted total knee replacement for medial
      compartment knee arthritis: a matched paired study.
AB  - Patients older than 60 with unicompartmental knee arthritis can be treated with
      total or unicompartmental knee replacement. The aim of this study was to compare
      the results of matched paired groups of patients with isolated medial compartment
      knee arthritis replaced with either UKR (group A) or computer-assisted TKR (group
      B). The results included 68 knees at a minimum follow-up of 3 years. All patients
      had a varus deformity no greater than 8 masculine and a BMI lower than 30.
      Patients were matched in terms of preoperative arthritis severity, age, gender
      and preoperative range of motion. In the computer-assisted TKR group, all the
      implants were positioned within 4 masculine of the correct hip-knee-ankle angle
      and frontal tibial component angle. The surgical time and hospital stay were
      statistically longer in the CA TKR group. During the study no implant required
      revision. The results showed higher scores for a UKR in the treatment of isolated
      primary unicompartmental knee arthritis in patients older than 60 compared to a
      computer-assisted TKR. In this study a computer-assisted alignment system for TKR
      with optimal implant positioning did not produce equivalent clinical results
      compared to a UKR, but did increase the financial costs.

PMID- 16896872
TI  - Morphological analysis of the proximal femur using quantitative computed
      tomography.
AB  - The anatomy of the proximal femur was studied in 35 specimens using quantitative
      computed tomography (QCT) and compared with anatomical sections studied by plane
      radiography and gross dissection. We found the primary supporting structure of
      the femoral head to be the primary compressive strut, which is a dense column of
      trabecular bone projecting from the pressure buttress of the medial femoral neck
      to the epiphyseal scar. Trabecular bone mushroomed from the epiphyseal scar and
      terminated at right angles to the cortex of the femoral head. We believe the
      primary compressive strut is the predominant load-bearing structure connecting
      the femoral head to the femoral neck, as many specimens lacked continuity of the
      head cortex to the femoral neck. Based on the CT number, the primary compressive
      strut had similar bone density to cortical structures such as the lesser
      trochanter, calcar femorale and posterior lateral femoral cortex. Ward's triangle
      lacked structural integrity in many cases, and we doubt the significance of
      tensile trabculae for sharing load. Surgical techniques such as femoral fracture
      fixation, resurfacing hip arthroplasty and allograft transplantation may benefit
      from this knowledge.

PMID- 16896873
TI  - K-wire transfixation or distraction following the Keller-Brandes arthroplasty in
      Hallux rigidus and Hallux valgus?
AB  - A total of 118 feet with Hallux valgus and Hallux rigidus treated by the Keller
      Brandes method were re-examined clinically and radiologically after 9.1 years
      (range: 1.7-24.3). Correction of the Hallux valgus angle was obtained from an
      average of 40 degrees to 23 degrees in the Hallux valgus group. Improvement in
      the postoperative range of motion was observed when the aftertreatment consisted
      of Kirschner-wire distraction instead of an axial Kirschner-wire transfixation.
      The patients who underwent Keller-Brandes surgery for Hallux valgus had less pain
      when the aftertreatment was carried out using an axial Kirschner wire, while
      those operated on for Hallux rigidus had less pain when the aftertreatment
      consisted of distraction. The percentage of satisfied or very satisfied patients
      with the cosmetic results of the Keller-Brandes arthroplasty was more than 66.7%.
      Patients with Hallux valgus and postoperative aftertreatment with Kirschner wire
      transfixation were the most satisfied patients, while patients with Hallux
      rigidus were very satisfied with the postoperative distraction. Our good results
      are comparable to those in other studies and confirm the success of the Keller
      Brandes resection arthroplasty in Hallux valgus with osteoarthritis of the first
      metatarsophalangeal joint in older patients whose demand for movement is less,
      and in Hallux rigidus in less active older patients.

PMID- 16896874
TI  - Microcurrent skin patches for postoperative pain control in total knee
      arthroplasty: a pilot study.
AB  - Pain control following painful orthopaedic procedures such as total knee
      arthroplasty (TKA) is an ongoing challenge, as current pain management techniques
      often result in under-medication and/or complications. In a study designed to
      test the effect of the micro-current skin patch (MCT) on pain relief in patients
      following TKA, we followed 24 patients, randomly divided into two groups, one
      group receiving MCT plus tramadol hydrochloride (tramadol) for pain relief and a
      control group receiving only tramadol, for 10 days postoperatively. Tramadol was
      given intramuscularly in increment doses of 100 mg, as needed, for the duration
      of the study period. Pain was assessed daily using a visual analogue score (VAS).
      Other parameters, including the effect of MCT on the dose of tramadol needed for
      pain relief, the degree of wound healing measured at the end of the follow-up
      period, category of the wound 10 days postoperatively (1, 2 or 3) and total drain
      fluid volume, were also assessed. During the 10-day postoperative period there
      was a progressive decrease in pain in patients of both groups, however the
      patients of the MCT group showed a consistently lower VAS throughout the
      observation period, most markedly on those follow-up days with the highest pain
      scores in patients of the control group. This effect was monitored on the basis
      of the average dose of tramadol administered per day: 200.0+/-7.0 mg/day in the
      control group and 63.3+/-15.8 mg/day in the MCT group. Wound healing was better
      with the application of the MCT patch: grade 1 wounds were observed in 50% of the
      patients of the MCT group as compared to 8.3% in control group. The total drain
      volume was lower in patients of the MCT group compared to the controls (1020.8+/
      211.6 and 1170.8+/-243.5 ml, respectively). None of the patients indicated that
      they wished to discontinue MCT therapy. This pilot study shows that MCT therapy
      led to better pain control with a markedly lower need for tramadol as compared to
      the control group. This better pain control was accompanied by a better healing
      of the wound and a lower drain volume.

PMID- 16896876
TI  - Transfusion of autologous blood from reinfusion systems in total knee
      arthroplasty.
AB  - After total knee arthroplasty (TKA) the technique of wound management is not
      standardised. In this prospective study the efficacy of autologous blood
      reinfusion from the wound was investigated. One hundred patients (100 TKAs) were
      enrolled in this sequential cohort study. In one-half of the operations, a
      reinfusion system with suction and in the other half one wound drain without
      suction were used. Blood loss, transfusion requirements, range of motion, Insall
      scores and the incidence of complications were studied. The use of a reinfusion
      system did not decrease the homologous transfusion requirements. The blood loss
      in the group with a suction drainage system was significantly higher. Our
      experiences since May 2002 with one drain without suction in 787 consecutive TKAs
      confirm all findings of the current study.

PMID- 16896875
TI  - Local control of long bone giant cell tumour using curettage, burring and bone
      grafting without adjuvant therapy.
AB  - Giant cell tumour (GCT) is a benign, but aggressive, primary tumour of the bone.
      The recurrence rate after surgical treatment has been reported to be as high as
      50%. Many surgical techniques have been employed in the treatment of this tumour.
      More aggressive interventions, such as en bloc resection and bulk allograft or
      prosthetic reconstruction, are generally understood to be associated with lower
      rates of local recurrence. However, because of lessened morbidity, intralesional
      techniques have come to be favoured for this condition. In addition to curettage,
      various adjuvant procedures and packing materials have been advocated in order to
      control and reconstruct long bone defects secondary to this neoplasm. We report
      our experience with 40 long bone GCT patients treated with curettage, burring,
      bone grafting and no adjuvants between 1997 and 2002. There was a local
      recurrence rate of 32.5%, with most recurrences noted within the first 30 months
      after surgery. Minor complications were found in 18% of patients. The risk of
      local recurrence in this study is acceptable (within the range that has been
      historically reported for curettage and bone grafting). In cases where more
      resources are available, the addition of adjuvant therapies, as noted in the
      recent literature, may be beneficial. The results of this study should be
      considered when designing multicenteric studies in the future.

PMID- 16896877
TI  - The microbiology of infected hip arthroplasty.
AB  - Infection following joint replacement surgery although rare presents a
      challenging problem. Bacterial resistance to antibiotics is an emerging problem.
      We analysed the microbiology of 337 single-stage revisions for deep infection.
      Coagulase negative staphylococcus was found to be the predominant organism,
      although staphylococcus aureus is gaining importance. Gentamicin only provides
      cover for 64.1% of organisms. Resistance to this commonly used antibiotic
      prophylaxis is escalating. Fusidic acid and erythromycin provide improved cover.
      We would suggest on a microbiological basis that these antibiotics be considered
      for addition to acrylic bone cement. This will provide local antibiotic delivery
      when performing a revision for deep infection.

PMID- 16896878
TI  - Financial and family burden associated with cancer treatment in Ontario, Canada.
AB  - GOALS OF WORK: To determine the financial and family resources burden associated
      with the treatment of cancer. A questionnaire was developed to determine the
      direct monthly "out-of-pocket costs" (OOPC), the indirect costs, and the
      associated perceived family burden. MATERIALS AND METHODS: A self-administered
      questionnaire using a quota sample from five cancer clinics in Ontario, Canada
      was given to 282 cancer patients (74 breast, 70 colorectal, 68 lung, and 70
      prostate). Monthly OOPC were obtained for: drugs, home care, homemaking,
      complementary and alternative medicines, vitamins and supplements, family care,
      travel, parking, accommodations, devices, and others. The questionnaire asked if
      OOPC for treatment were a burden, and if others took time from work to provide
      caregiving. MAIN RESULTS: The mean monthly OOPC was $213, with an additional $372
      related to imputed travel costs. For those patients who responded that the burden
      was "significant" (16.5%), their OOPC was $452. In the case of patients
      responding that their burden was "unmanageable" (3.9%), their OOPC was $544. The
      survey showed that 35.6% of patients required others to take time from work and
      this was higher in the under-65 category. The mean number of days lost from work
      in the previous 30 days for these caregivers was 7 days. CONCLUSIONS: These
      results suggest the financial burden is problematic for 20% of this sample. The
      caregivers' lost time from work influence this burden, and for 36% of this
      sample, it amounts to one third of their working days in any given month.
      Policies and programs to address these gaps are needed.

PMID- 16896879
TI  - Distress before chemotherapy predicts delayed but not acute nausea.
AB  - INTRODUCTION: Posttreatment nausea (PTN) is a common side effect of cytotoxic
      cancer chemotherapy. Previous retrospective research has suggested that the
      severity of PTN may be, in part, related to pretreatment psychological factors
      (e.g., emotional distress and expectations for nausea). MATERIALS AND METHODS:
      The purpose of the present study was to examine these relationships
      prospectively, with distress and nausea expectations assessed by validated self
      report measures completed in the clinic before the participants' first outpatient
      treatment infusion and with PTN (0-100) assessed by end-of-day diaries completed
      at home on each of the first 5 days after treatment. The participants were
      chemotherapy-naive women (N=56) scheduled for standard adjuvant treatment for
      stage I-II breast cancer (mean age=45.6 years). PTN was evaluated for acute (days
      0-1) and delayed (days 2-5) responses. RESULTS: The results revealed a
      significant relationship between pretreatment distress and the severity of the
      patients' subsequent delayed nausea (p<0.007) but not a relationship with acute
      PTN (p<0.19). No significant relationships were seen between expectations and
      PTN. However, there was evidence of an additive effect of nausea expectations and
      distress, with the highest levels of delayed PTN seen in patients with both
      expectations and higher distress before treatment. The results suggest a
      selective effect of pre-infusion psychological variables on the delayed phase of
      nausea after chemotherapy, consistent with an emerging view that the different
      phases of nausea are mediated by different neural pathways. CONCLUSION: Future
      research should examine the possibility that delayed nausea, which the literature
      suggests is more resistant to antiemetic drugs than acute nausea, might be
      responsive to psychological interventions before initial treatments.

PMID- 16896880
TI  - Emetic potential of daily oral etoposide.
AB  - BACKGROUND: Chemotherapeutic agents are classified by their degree of
      emetogenicity. Highly and moderately emetogenic agents require antiemetic
      prophylaxis for chemotherapy-induced nausea and vomiting. Intravenous etoposide
      is listed as having low emetic potential. However, oral etoposide is categorized
      as having moderate emetogenicity. Daily oral etoposide is used in refractory germ
      cell cancer patients. We prospectively evaluated the emetic potential of oral
      etoposide in this patient population. MATERIALS AND METHODS: Between August 2003
      and February 2006, 16 patients with refractory germ cell cancer received single
      agent, daily oral etoposide 50 mg/M(2) for 21 consecutive days every 4 weeks. All
      patients had progressed after cisplatin combination chemotherapy and had received
      high-dose chemotherapy with carboplatin plus etoposide (intravenously) with
      peripheral blood stem cell transplant. No patient received prophylactic
      antiemetics. Patients completed a six-question Multinational Association of
      Supportive Care in Cancer (MASCC) antiemetic tool during each day of etoposide
      during the first 21-day course. Nausea intensity and duration were recorded.
      Number of emetic episodes and any antiemetic medications were recorded. RESULTS:
      All 16 patients completed the six-question MASCC form. Eleven of 16 had no nausea
      or vomiting and two other patients had only minimal nausea, despite absence of
      any prophylactic antiemetics. Only two patients required antiemetic support. Two
      patients experienced emesis for a single episode. One patient had nausea on days
      9-20 with a MASCC rating of 3-6, and one patient had continued mild nausea (MASCC
      rating 1-3) for all 21 days. CONCLUSIONS: Daily oral etoposide has a low
      probability of producing chemotherapy-induced nausea and/or vomiting and, in our
      opinion, does not require prophylactic antiemetics.

PMID- 16896881
TI  - Palifermin improves severe mucositis, swallowing problems, nutrition impact
      symptoms, and length of stay in patients undergoing hematopoietic stem cell
      transplantation.
AB  - GOAL OF WORK: The aim of this study was to compare palifermin, a recombinant form
      of human keratinocyte growth factor, with standard treatment on outcomes in
      patients receiving a high dose of chemotherapy conditioning regimen, undergoing
      hematopoietic stem cell transplantation (HSCT). MATERIALS AND METHODS: Over a 1
      year period, a series of 59 patients were included: 32 patients (palifermin) were
      compared with 27 patients (standard treatment). Outcomes assessed at day 8
      posttransplantation were mucositis, swallowing, nutrition impact symptoms,
      dietary intake, time to engraftment, length of stay, infection, and cumulative
      dose and duration of narcotic administration. MAIN RESULTS: There was a
      significant reduction in the incidence of severe oral mucositis (13 vs 48%,
      p=0.003), swallowing problems (p=0.044), number of nutrition impact symptoms
      experienced (4.9 vs 6.0, p=0.003), and length of stay (14 vs 18 days, p=0.026) in
      the palifermin group compared to standard care. There was no significant
      difference in infection, dietary intake, time to engraftment or cumulative dose
      and duration of narcotic administration between groups. CONCLUSIONS: Beneficial
      outcomes were observed from the use of palifermin in patients undergoing HSCT
      after a high dose of chemotherapy conditioning regimen. A randomized clinical
      trial is needed to confirm these results.

PMID- 16896882
TI  - Report on trends of incidence (1970-2002) of and mortality (1952-2002) from
      cancer in Germany.
AB  - PURPOSE: The paper presents the statistical analysis of current and past trends
      of cancer mortality rates in Germany in terms of annual percent change, overall
      and for the major sites, and contrasts them with trends in incidence of the
      Cancer Registry of the Saarland, the only registry in this country with long-term
      completeness. It addresses also the issue of a cross-over of cancer mortality and
      mortality from cardiovascular diseases (CVD) in the near future, as suggested by
      various authors. MATERIAL AND METHODS: Analyses are based on the mortality data
      of the official mortality statistics as published by the Federal Statistical
      Office and reported annually to the WHO, and the regularly reported incidence
      data of the Cancer Registry of the Saarland. The data was age-standardised and
      analysed by piecewise regression using a freely available dedicated software
      package. RESULTS: The report shows a downward trend of mortality rates for all
      cancers combined based on declining rates for many individual sites with only few
      exceptions affecting mainly females (e.g. lung cancer). Recently, the long-term
      increase of cancer incidence also flattened out with rather heterogeneous
      underlying site-specific trends increasing for some sites (e.g. cancers of the
      intestine, breast, prostate, or some lymphoma) and decreasing for others (e.g.
      cancers of the stomach, gall bladder in females, larynx, and lung in males). A
      crossover of cancer mortality and mortality from CVD might occur-if at all-after
      2,020 in males and 2,030 in females. CONCLUSIONS: Depending on cancer site,
      primary prevention (e.g. lung cancer among males), early detection (cervical
      cancer), and treatment (e.g. breast and testicular cancer, lymphoma) contributed
      to the current decline of mortality rates. Absence of a turnaround (e.g. lung
      cancer among females), slower decline than in other countries (e.g. cervical
      cancer), or later turnaround (e.g. breast cancer) may be related to failures in
      promoting prevention (lung cancer among females), early detection programmes
      (cervical cancer), or delays in the translation of modern treatment into routine
      health care (breast cancer) and indicate major challenges for current and future
      health policy.

PMID- 16896883
TI  - What implications do the tolerability profiles of antiandrogens and other
      commonly used prostate cancer treatments have on patient care?
AB  - PURPOSE: Increased awareness of prostate cancer has led to earlier initiation of
      therapy, and the potential for a longer duration of treatment has led to a
      stronger emphasis on tolerability. Historically, the mainstay of treatment of
      hormone-sensitive prostate cancer has been castration-based therapy, but
      antiandrogens are now emerging as an alternative. This article reviews the
      tolerability profiles of antiandrogens as well as other existing treatments for
      prostate cancer and examines their implications on patient care. METHODS: A
      search of online literature databases was conducted to identify recent articles
      and studies (1990-2006) that have reported adverse effects associated with
      treatment approaches for men with prostate cancer. The therapies reviewed here
      include castration, antiandrogens, a combination of castration and antiandrogens
      (CAB), estrogens, and chemotherapy. RESULTS: Castration offers significant
      clinical benefits when used as monotherapy or as adjuvant therapy; however, it is
      associated with loss of bone mineral density, and a reduction in physical
      activity and sexual function, which can have a negative impact on quality of
      life. Detrimental effects on muscle mass, fat deposition, and cognitive function
      have also been reported. Recent data suggest that the non-steroidal antiandrogen,
      bicalutamide, confers a significant overall survival benefit when used as
      adjuvant to radiotherapy in patients with locally advanced disease. However, the
      survival data for bicalutamide are not as extensive as those available for LHRH
      agonists. Although they do not appear to have a significant impact on sexual and
      physical activity, non-steroidal antiandrogens are frequently associated with
      gynecomastia and breast pain, and some are associated with diarrhea. Estrogens
      have been used in patients with androgen-independent prostate cancer; however,
      cardiovascular toxicity has restricted their use. In patients whose prostate
      cancer has become hormone-refractory, treatment options include chemotherapeutic
      agents, such as docetaxel and mitoxantrone. CONCLUSIONS: It is important for
      physicians to discuss the adverse effects of all the available treatment options
      with patients so that a therapy can be selected to meet their expectations in
      terms of overall survival and tolerability.

PMID- 16896885
TI  - What is the role of antiandrogen therapy in the treatment of prostate cancer?

PMID- 16896884
TI  - The addition of bicalutamide 150 mg to radiotherapy significantly improves
      overall survival in men with locally advanced prostate cancer.
AB  - PURPOSE: Castration therapy adjuvant to radiotherapy can significantly improve
      overall survival compared with radiotherapy alone in patients with locally
      advanced prostate cancer. Although many of the adverse effects of castration
      therapy are manageable, they can have a detrimental effect on quality of life.
      Here we evaluate the efficacy and tolerability of the non-castration-based
      therapy bicalutamide ('Casodex') 150 mg adjuvant to radiotherapy in patients with
      T1-4, M0, any n prostate cancer. METHODS: The subset of patients within the early
      prostate cancer (EPC) program who received radiotherapy with curative intent (n =
      1,370) were included in the analysis. These patients were randomized to receive
      oral bicalutamide 150 mg once daily (n = 699) or placebo (n = 671). RESULTS: The
      median follow-up for patients included in this analysis was 7.2 years. In
      patients with locally advanced disease (n = 305), bicalutamide adjuvant to
      radiotherapy significantly improved: progression-free survival (PFS), reducing
      the risk of objective progression by 44% compared with radiotherapy alone [hazard
      ratio (HR) 0.56; 95% confidence interval (CI) 0.40, 0.78; P < 0.001). Prostate
      specific antigen (PSA)-PFS, reducing the risk of PSA progression by 59% compared
      with radiotherapy alone (HR 0.41; 95% CI 0.30, 0.55; P < 0.001). Overall
      survival, reducing the risk of death by 35% compared with radiotherapy alone (HR
      0.65; 95% CI 0.44, 0.95; P = 0.03). This significant overall survival benefit for
      bicalutamide was driven by a lower risk of prostate cancer-related deaths (16.1
      vs 24.3%, respectively). There was no significant difference in PFS or overall
      survival in patients with localized disease (n = 1,065). CONCLUSIONS: In patients
      with locally advanced disease, bicalutamide 150 mg adjuvant to radiotherapy
      demonstrates significant clinical benefits in terms of overall survival, PFS and
      PSA-PFS compared with radiotherapy alone. The overall survival benefit in these
      patients is consistent with prior studies evaluating castration-based therapies
      adjuvant to radiotherapy (Bolla et al. in Lancet 360:103-108, 2002; Pilepich et
      al. in Int J Radiat Oncol Biol Phys 61:1285-1290, 2005). In addition, the
      clinical benefit of bicalutamide 150 mg in locally advanced patients, but not in
      those with localized disease, is consistent with the overall results from the EPC
      program (McLeod et al. BJU Int 97:247-254, 2006). Given the quality-of-life
      advantages of bicalutamide relative to castration, bicalutamide 150 mg adjuvant
      to radiotherapy is an attractive alternative for men with locally advanced
      prostate cancer.

PMID- 16896886
TI  - Theoretical, numerical, and experimental modal analysis of a single-winding
      gradient coil insert cylinder.
AB  - The objective of this paper is to find the relatively low-frequency (200-2,000
      Hz) mode shapes of a single-winding gradient coil cylinder with intermediate wall
      thickness. The dynamic behavior of a gradient coil cylinder plays a crucial role
      in determining and controlling the vibroacoustic performance of magnetic
      resonance imaging (MRI) scanners. Modal analyses of the gradient coil cylinder
      were carried out under different boundary conditions to obtain the various mode
      shapes. Theoretical modes, predicted by using modified Love's governing
      equations, and numerical modes simulated using a finite element method show close
      agreement with experimental modal results and reveal the mode shapes for both
      free-end and fixed-end boundary conditions. These results were further compared
      to in situ measurements of the mode shapes of the gradient coil cylinder insert
      during scanning in a 4 Tesla MRI. The general agreement among the analytical,
      numerical, and experimental mode shapes indicates that a linear combination of
      basic beam vibration and ring vibration patterns occupy the dynamic vibration
      modes in the low frequency range. The in situ vibration measurements show that
      the forcing function developed by the distributed Lorentz forces on the surface
      of the single-winding gradient coil results in predominantly beam-type bending
      mode patterns in the low frequency range.

PMID- 16896887
TI  - Optimized diffusion gradient orientation schemes for corrupted clinical DTI data
      sets.
AB  - OBJECT: A method is proposed for generating schemes of diffusion gradient
      orientations which allow the diffusion tensor to be reconstructed from partial
      data sets in clinical DT-MRI, should the acquisition be corrupted or terminated
      before completion because of patient motion. MATERIALS AND METHODS: A general
      energy-minimization electrostatic model was developed in which the interactions
      between orientations are weighted according to their temporal order during
      acquisition. In this report, two corruption scenarios were specifically
      considered for generating relatively uniform schemes of 18 and 60 orientations,
      with useful subsets of 6 and 15 orientations. The sets and subsets were compared
      to conventional sets through their energy, condition number and rotational
      invariance. Schemes of 18 orientations were tested on a volunteer. RESULTS: The
      optimized sets were similar to uniform sets in terms of energy, condition number
      and rotational invariance, whether the complete set or only a subset was
      considered. Diffusion maps obtained in vivo were close to those for uniform sets
      whatever the acquisition time was. This was not the case with conventional
      schemes, whose subset uniformity was insufficient. CONCLUSION: With the proposed
      approach, sets of orientations responding to several corruption scenarios can be
      generated, which is potentially useful for imaging uncooperative patients or
      infants.

PMID- 16896888
TI  - Primary intracranial leiomyoma: a case report and literature review.
AB  - We report a case of primary intracranial leiomyoma in 29-year-old woman presented
      with severe headache. The radiology diagnosis was consistent with meningioma.
      However, histologically, the tumor had the characteristic appearance of benign
      smooth muscle. This was confirmed by immunohistochemistry and electron
      microscopy. Benign metastasizing leiomyoma was excluded by thorough imaging.
      Although rare, leiomyoma should be considered in the differential diagnosis of
      well-circumscribed intracranial lesion.

PMID- 16896889
TI  - Tumor of the liver (hepatocellular and high grade neuroendocrine carcinoma): a
      case report and review of the literature.
AB  - We describe a rare hepatic collision tumor composed of a hepatocellular carcinoma
      and a high-grade neuroendocrine carcinoma. The patient, a 50-year-old man,
      underwent a partial hepatectomy because of a 5.0-cm mass. The tumor had two
      distinctive patterns. The majority of the tumor was a high-grade neuroendocrine
      carcinoma with features of a small cell carcinoma that was positive for
      chromogranin, synaptophysin, and cytokeratin 19 and negative for hepatocellular
      antigen and alpha-fetoprotein (AFP). The second component was a moderately
      differentiated hepatocellular carcinoma that was positive for hepatocellular
      antigen and AFP and negative for neuroendocrine markers. The two tumors were
      separated by fibrous bands. In areas where they collided, there was no transition
      or intermingling of cells between the two components, thus, it is different from
      the combined type of tumors. After removal of the tumor, the patient had
      intrahepatic and mesenteric recurrences within a follow-up period of 16 months.

PMID- 16896891
TI  - Nephrogenic fibrosing dermopathy with involvement of the dura mater.

PMID- 16896890
TI  - Conjugated linoleic acid reduced metastasized LL2 tumors in mouse peritoneum.
AB  - The effect of conjugated linoleic acid (CLA) on pre-existent peritoneal
      metastasis was examined by mouse peritoneal metastasis models. The cell growth of
      LL2 mouse cancer cells was suppressed by CLA in a dose-dependent manner. CLA
      induced growth inhibition was recovered by the exposure to antisense S
      oligodeoxynucleotide for peroxisome proliferator-activated receptor (PPAR)-gamma.
      C57B6 mice were inoculated with LL2 cells into their peritoneal cavity. Two weeks
      after inoculation, colonized peritoneal cancer foci (2.2+/-0.4 mm in diameter)
      were treated with CLA administrated intraperitoneally (200 or 600 pmol/mouse,
      twice a week). CLA treatment decreased the number of peritoneal tumors: 8.7+/
      0.6, 5.7+/-0.6, and 2.3+/-0.6 in untreated, 200 pmol/mouse CLA, and 600
      pmol/mouse CLA groups, respectively (P<0.0001). CLA treatment decreased the size
      of peritoneal tumors: 3.7+/-1.5, 1.3+/-0.5, and 1.0+/-0.4 mm in untreated, 200
      pmol/mouse CLA, and 600 pmol/mouse CLA groups, respectively (P<0.0001). In CLA
      treated tumors, proliferating cells were decreased (P<0.0001), whereas apoptotic
      cells were increased (P=0.0010). CLA-treated LL2 tumors showed decrease of
      PPARgamma and EGFR proteins and increase of BAX protein in comparison with
      untreated tumors. These findings suggest that CLA possesses anti-tumor capability
      to peritoneal metastasis.

PMID- 16896893
TI  - A malignant mucinous cystic neoplasm arising within a mycrocystic adenoma of the
      pancreas.

PMID- 16896892
TI  - The high frequency of EBV infection in pediatric Hodgkin lymphoma is related to
      the classical type in Bahia, Brazil.
AB  - Pediatric Hodgkin lymphoma (HL) occurring in developing regions is different from
      HL in industrialized countries due to the higher frequency of association with
      Epstein-Barr virus (EBV) infection. This infection is related to classical HL
      (cHL) but is virtually absent in nodular lymphocyte predominant HL (nLPHL). We
      studied the phenotype and the expression of EBV gene products in 90 pediatric
      cases by immunohistochemistry and in situ hybridization. EBV-positive tumor cells
      were found exclusively in cHL. The infection occurred with high frequency in all
      cHL subtypes, but it predominated in the mixed cellularity and lymphocyte
      depletion subtypes. These results reinforce the hypothesis that EBV plays a major
      role in the etiology of pediatric cHL in developing areas. Curiously, the
      frequency of EBV infection in HL was identical to the previously described for
      Burkitt's lymphoma in the same pediatric population. As both lymphomas have a
      postulated precursor cell in the germinal center (GC), the pattern of latently
      EBV-infected GC cells previously described in Bahia may be related to the
      development of these lymphomas.

PMID- 16896894
TI  - Oncofetal protein glypican-3 in testicular germ-cell tumor.
AB  - The expression of an oncofetal protein, the glypican-3 (GPC3), was
      immunohistochemically evaluated in a wide variety of primary testicular germ-cell
      tumors (GCTs) in comparison with other markers, alpha-fetoprotein (AFP), human
      chorionic gonadotropin (hCG)-beta, and OCT3/4. Eighty-nine cases of GCT including
      22 cases of mixed GCT were evaluated with reference to each tumor component. GPC3
      expression was observed in neoplastic cells of yolk-sac tumor (YST) (25/25),
      teratoma (2/10), components of syncytiotrophoblastic giant cells (STGCs) (10/14),
      and choriocarcinoma (1/3), but none in intratubular germ-cell neoplasias,
      unclassified type (0/33), seminomas (0/61), or embryonal carcinoma (0/19). All
      cases of YST showed diffuse labeling of neoplastic cells in cytoplasmic and
      membranous patterns, and the positive area of GPC3 was much larger than that of
      AFP. Glandular structures in teratomas showed GPC3 immunostaining as well as AFP.
      Although the number of GPC3-positive cells was smaller in STGC components and
      choriocarcinoma, there was no diffusion artifact in GPC3 immunostaining, as was
      frequently encountered in hCG-beta staining. Thus, GPC3 is a unique oncofetal
      protein, which is useful as an immunohistochemical marker for GCT differentiated
      to extraembryonic tissue, especially YST.

PMID- 16896895
TI  - Morphometric sum optical density as a surrogate marker for ploidy status in
      prostate cancer: an analysis in 180 biopsies using logistic regression and binary
      recursive partitioning.
AB  - We sought to identify morphometric descriptors predictive of nondiploidy in
      prostatic adenocarcinoma on prostate needle biopsies using logistic regression
      (LR) and binary recursive partitioning (BRP) and compare the equivalence of both
      methods. A total of 180 prostate needle biopsies diagnosed as prostatic
      adenocarcinoma were selected. Deoxyribonucleic acid ploidy and morphometry were
      performed separately on Feulgen-stained sections from these biopsies using the
      CAS-200 system and Nuclear Morphometry Suite, respectively. Seven morphometric
      predictors were tested as predictor variables, including nuclear area,
      circularity, elongation, sum optical density (OD), configuration run length,
      coefficient of variation (CV), and angularity. Logistic regression (LR)
      identified a two-parameter model including sum OD and circularity that had a
      93.9% overall correct prediction rate (area under curve=0.950; 95% CI: 0.913,
      0.987). A reduced model including only sum OD was equally good without any
      significant loss of predictive accuracy (93.3% correct overall classification
      rate). BRP also selected sum OD as the most predictive parameter; a sum OD cut
      off of 7.73 in this model identified 93.3% of the nondiploid cases correctly.
      Morphometric OD can be used as a surrogate marker of nondiploidy. LR and BRP
      models are both equivalent in identifying and correctly classifying nondiploid
      cases of prostate cancer using sum OD as the predictor variable.

PMID- 16896896
TI  - [Pelvic and perineal trauma. Diagnosis and interventional radiotherapy].
AB  - The integration of multislice CT (MSCT) in the imaging of emergency trauma has
      led to a paradigm shift in trauma management. In case of hemodynamically instable
      patients, initial imaging is limited to a small set of standardized radiographs.
      Computed tomography is the imaging modality of choice for further diagnostic work
      up. Consequently it should be used at an early stage and in a less restricted
      manner for complete assessment of the pelvic injury and to determine therapeutic
      management. The MSCT allows full assessment of bone, parenchymal, and vascular
      injuries in a single examination in the shortest time possible. High-resolution
      3D imaging provides additional options. There is increasing support for primary
      use of MSCT in critically ill patients due to the comprehensive imaging it allows
      while maintaining a fast scan time. The potential and limitations of diagnostic
      imaging in pelvic ring fracture and associated injuries are explained.
      Indications for vascular interventions in arterial bleeding are discussed.

PMID- 16896897
TI  - [Management of trauma to the male external genitalia].
AB  - Male genital injury, although rarely life-threatening, demands prompt,
      appropriate management to prevent long-term sexual and psychological damage.
      However, because of the rarity and disparity of severe genital injuries, there is
      still no universal therapeutic strategy. Urethral injury, although rare, may be
      associated with substantial long-term morbidity such as fistulas and strictures.
      Injuries to the scrotum and its contents may cause impaired fertility, chronic
      pain, hypogonadism, and altered self-image. Penile injury may lead to pain,
      curvature, and erectile dysfunction. This article concentrates on reviewing the
      major etiologies and mechanisms of urethral and genital injuries in men and
      summarizes principles and strategies of treatment based on the guidelines of the
      European Association of Urology.

PMID- 16896898
TI  - [Blunt pelvic injury].
AB  - Life-threatening complex pelvic fractures are commonly associated with vast
      peripelvine soft-tissue injuries and hemorrhage. Correct assessment and
      classification of the existing pelvic trauma and additional severe injuries
      present is required for accurate diagnosis and effective therapy. Treatment of
      the usually multiply injured patient is time-sensitive. The circulatory situation
      is the benchmark for diagnostic and therapeutic actions. Emergency stabilization
      of an initially unstable pelvic ring should be done first, followed by an
      extraperitoneal tamponade, if needed to control bleeding. The positive results of
      these actions can be measured by hemodynamic parameters. Delayed definitive
      internal stabilization of the anterior and/or posterior pelvic ring is then
      performed according to the fracture classification.

PMID- 16896899
TI  - [Perianal and rectal impalement injuries].
AB  - Perianal impalement injuries with or without involvement of the anorectum are
      rare. Apart from a high variety of injury patterns, there is a multiplicity of
      diagnostic and therapeutic options. Causes of perianal impalement injury are
      gunshot, accidents, and medical treatment. The diagnostic work-up includes
      digital rectal examination followed by rectoscopy and flexible endoscopy under
      anaesthesia. We propose a new classification for primary extraperitoneal perianal
      impalement injuries in four stages in which the extension of sphincter and/or
      rectum injury is of crucial importance. Therapeutic aspects such as wound
      treatment, enterostomy, drains, and antibiotic treatment are discussed. The
      proposed classification encompasses recommendations for stage-adapted management
      and prognosis of these rare injuries.

PMID- 16896901
TI  - [Effect of cigarette smoking on skin perfusion of the hand].
AB  - BACKGROUND: Cigarette consumption leads to postoperative wound healing
      disturbances by impairing skin circulation. MATERIALS AND METHODS: Fourteen
      nonsmokers and 44 smokers were investigated and classified according to age (<40
      and >40 years) and duration of cigarette consumption. Circulation at the tip of
      the middle finger was measured in both groups under standard conditions with
      laser Doppler imaging. RESULTS: There was a reduction in skin blood circulation
      of 24% in smokers (young 39%, older 11%, P=0.001) and 30% in nonsmokers (young
      35%, older 18%, P=0.019). With longer duration of cigarette consumption, the
      effect grew weaker (<10 years 25%, 11-30 years 18%, >30 years 15%). There was no
      correlation between the number of cigarettes consumed per day and impaired
      circulation. CONCLUSION: Younger subjects react to cigarette consumption with a
      stronger reduction in circulation. In elective surgery, especially in young
      smokers we recommend a 6- to 8-week nicotine abstinence prior to surgical
      intervention.

PMID- 16896902
TI  - Transferrin localizes in Bunina bodies in amyotrophic lateral sclerosis.
AB  - Transferrin, an iron-binding protein, plays an important role in the transport
      and delivery of circulating ferric iron to the tissues. Amyotrophic lateral
      sclerosis (ALS) is characterized by the presence of Bunina bodies, skein-like
      inclusions, Lewy body-like inclusions/round inclusions, and basophilic inclusions
      in the remaining anterior horn cells in the spinal cord. We examined transverse
      paraffin sections of lumbar spinal cords from 12 ALS cases including two ALS with
      dementia and two ALS with basophilic inclusions, using antibodies to human
      transferrin. The results demonstrated that transferrin localized in Bunina bodies
      and some of the basophilic inclusions. In contrast, skein-like inclusions and
      Lewy body-like inclusions or round inclusions did not show obviously detectable
      transferrin immunoreactivities. Our findings suggest that although the mechanisms
      underlying transferrin accumulation in Bunina bodies and basophilic inclusions
      are unknown, transferrin could be involved in forming these inclusions.
      Furthermore, following cystatin C, transferrin is the second protein that
      localizes in the Bunina bodies.

PMID- 16896900
TI  - [Dynamic graciloplasty vs artificial bowel sphincter in the management of severe
      fecal incontinence].
AB  - Dynamic graciloplasty (DGP) and the Acticon Neosphincter (artificial bowel
      sphincter, ABS) are well-established therapeutic instruments in patients with
      severe fecal incontinence. However, the success rates in the literature must be
      interpreted with caution. The report presented here presents firstly a critical
      analysis of 1510 patients in 52 studies (29 DGP vs 23 ABS). The evidence of these
      studies was assessed using the Oxford EBM criteria. All data were statistically
      analysed. Up to 94% of the studies analysed show EBM levels of only >3b. Both
      procedures show significant improvements in postoperative continence scores
      (p<0.001) and a significant advantage of ABS over DGP. Nevertheless, they are
      associated with a high incidence of morbidity in the long term (infection rate
      ABS vs DGP 21.74% vs 35.1%, revision rate ABS vs DGP 37.53% vs 40.64%, and ABS
      explantation rates of 30%). Presently no therapeutic recommendation can be
      expressed based on the few data available. Furthermore, therapy should be
      performed in specialized centers and patients should be given a realistic picture
      of the critical outcome of both surgical techniques.

PMID- 16896903
TI  - Anaplastic medulloblastoma with granular cell change.
AB  - Granular cell change secondary to lysosomal accumulation has been described in a
      variety of tumors of the nervous system of presumed glial or schwannian
      derivation. Herein we report the case of a 15-year-old female with an anaplastic
      medulloblastoma which histologically demonstrated areas with granular cell
      change. These granular cells co-expressed neuronal immunohistochemical markers,
      including synaptophysin, chromogranin, and Neu-N, and demonstrated accumulation
      of lysosomes and dense core granules in the same cells at the ultrastructural
      level. This unusual finding suggests that the spectrum of granular cell change
      should be expanded to include tumors with primarily neuronal differentiation.

PMID- 16896904
TI  - No evidence for epidermal growth factor receptor amplification and overexpression
      in atypical teratoid/rhabdoid tumors.

PMID- 16896906
TI  - Tentorial artery embolization in tentorial dural arteriovenous fistulas.
AB  - INTRODUCTION: The tentorial artery is often involved in arterial supply to
      tentorial dural fistulas. The hypertrophied tentorial artery is accessible to
      embolization, either with glue or with particles. METHODS: Six patients are
      presented with tentorial dural fistulas, mainly supplied by the tentorial artery.
      Two patients presented with intracranial hemorrhage, two with pulsatile tinnitus
      and one with progressive tetraparesis, and in one patient the tentorial dural
      fistula was an incidental finding. Different endovascular techniques were used to
      embolize the tentorial artery in the process of endovascular occlusion of the
      fistulas. RESULTS: All six tentorial dural fistulas were completely occluded by
      endovascular techniques, confirmed at follow-up angiography. There were no
      complications. When direct catheterization of the tentorial artery was possible,
      glue injection with temporary balloon occlusion of the internal carotid artery at
      the level of the tentorial artery origin was effective and safe. CONCLUSION:
      Different endovascular techniques may be successfully applied to embolize the
      tentorial artery in the treatment of tentorial dural fistulas.

PMID- 16896905
TI  - Glial degeneration and reactive gliosis in alpha-synucleinopathies: the emerging
      concept of primary gliodegeneration.
AB  - The concept of gliodegenerative diseases has not been widely established although
      there is accumulating evidence that glial cells may represent a primary target of
      degenerative disease processes. In the central nervous system (CNS), examples
      that provide a "proof of concept" include at least one alpha-synucleinopathy,
      multiple system atrophy (MSA), but this disease is conventionally discussed under
      the heading of "neurodegeneration". Additional evidence in support of primary
      glial affection has been reported in neurodegenerative disorders such as
      Parkinson's disease, Alzheimer's disease and transmissible spongiform
      encephalopathies. Based on biochemical, genetic and transcriptomic studies it is
      also becoming increasingly clear that the molecular changes measured in whole
      tissue extracts, e.g. obtained from Parkinson's disease brain, are not based on a
      purely neuronal contribution. This important evidence has been missed in cell
      culture or laser capture work focusing on the neuronal cell population. Studies
      of animal and in vitro models of disease pathogenesis additionally suggest glial
      accountability for some CNS degenerative processes. This review provides a
      critical analysis of the evidence available to date in support of the concept of
      gliodegeneration, which we propose to represent an essential although largely
      disregarded component of the spectrum of classical "neurodegeneration". Examples
      from the spectrum of alpha-synucleinopathies are presented.

PMID- 16896907
TI  - Meningiomas with conventional MRI findings resembling intraaxial tumors: can
      perfusion-weighted MRI be helpful in differentiation?
AB  - INTRODUCTION: To investigate the contribution of perfusion-weighted MRI to the
      differentiation of meningiomas with atypical conventional MRI findings from
      intraaxial tumors. METHODS: We retrospectively analyzed 54 meningiomas, 12
      glioblastomas and 13 solitary metastases. We detected 6 meningiomas with atypical
      features on conventional MRI resembling intraaxial tumors. The regional cerebral
      blood flow (rCBV) ratios of all tumors were calculated via perfusion-weighted
      MRI. The signal intensity-time curves were plotted and three different curve
      patterns were observed. The type 1 curve resembled normal brain parenchyma or the
      postenhancement part was minimally below the baseline, the type 2 curve was
      similar to the type 1 curve but with the postenhancement part above the baseline,
      and the type 3 curve had the postenhancement part below the baseline accompanied
      by widening of the curve. Student's t-test was used for statistical analysis.
      RESULTS: On CBV images meningiomas were hypervascular and the mean rCBV ratio was
      10.58+/-2.00. For glioblastomas and metastatic lesions, the rCBV ratios were
      5.02+/-1.40 and 4.68+/-1.54, respectively. There was a statistically significant
      difference in rCBV ratios between meningiomas and glioblastomas and metastases
      (P<0.001). Only one of the meningiomas displayed a type 2 curve while five showed
      a type 3 curve. Glioblastomas and metastases displayed either a type 1 or a type
      2 curve. None of the meningiomas showed a type 1 curve and none of the
      glioblastomas or metastases showed a type 3 curve. CONCLUSION: Differentiating
      meningiomas with atypical conventional MRI findings from malignant intraaxial
      tumors can be difficult. Calculation of rCBV ratios and construction of signal
      intensity-time curves may contribute to the differentiation of meningiomas from
      intraaxial tumors.

PMID- 16896909
TI  - Ictal SPECT in neocortical epilepsies: clinical usefulness and factors affecting
      the pattern of hyperperfusion.
AB  - INTRODUCTION: The aims of this analysis were to: (1) determine the value of ictal
      SPECT in the localization of neocortical epileptogenic foci, (2) evaluate the
      relationships between the results of ictal SPECT and other potential affecting
      factors, and (3) compare traditional visual analysis and the subtraction method.
      METHODS: We retrospectively analyzed 81 consecutive patients with neocortical
      epilepsy who underwent epilepsy surgery and achieved a favourable surgical
      outcome, including 36 patients with normal MRI. Side-by-side visual analysis and
      subtraction images were classified as correctly localizing,correctly
      lateralizing, or non-localizing/non-lateralizing images according to the resected
      lobe. RESULTS: Side-by-side visual analysis and subtraction SPECT correctly
      localized the epileptogenic lobe in 58.9% and 63.0% of patients, respectively.
      The two methods were complementary and the diagnostic sensitivity of ictal SPECT
      using the two methods was 79.0%. Ictal SPECT using the visual method correctly
      localized the epileptogenic lobe more frequently in patients with a localizing
      pattern of ictal scalp EEG at the time of radioligand injection. When using
      subtraction images, an injection delay of less than 20 s after seizure onset was
      significantly correlated with correct localization. The subtraction method was
      superior to the visual method for localizing frontal lobe epilepsy (FLE) and
      parietal lobe epilepsy (PLE), and in patients with non-localizing/non
      lateralizing EEG at onset. CONCLUSIONS: Ictal SPECT analyses using visual and
      subtraction methods are useful and complementary for the localization of the
      epileptogenic foci of neocortical epilepsy. Early radioligand injection and ictal
      EEG patterns are related to ictal SPECT localization. The subtraction method may
      be more useful in some epileptic syndromes.

PMID- 16896908
TI  - Virchow-Robin spaces on magnetic resonance images: normative data, their
      dilatation, and a review of the literature.
AB  - INTRODUCTION: Virchow-Robin spaces (VRS) are perivascular spaces in the brain and
      can be visualized on magnetic resonance images (MRI). We attempt to provide a
      better understanding of the significance of VRS for pathological and
      physiological processes by reviewing the literature, presenting normative data
      for the first time, and proposing a definition for the dilatation of the VRS on
      MRI that is based on shape rather than size. METHODS: We evaluated the VRS in 125
      healthy subjects (age range 1-30 years) using high-resolution 3D images, and in
      36 patients (age range 2-16 years) with normal MRI, using routine clinical
      sequences. RESULTS: VRS were visible in all high-resolution images of the 125
      healthy subjects. Two of them revealed dilated VRS, giving a prevalence of 1.6%.
      VRS could be visualized in 29 (80%) of the 36 paediatric clinical scans; none was
      dilated. It was demonstrated that the visibility of VRS on MRI is sequence
      dependent. CONCLUSION: From the results of this study and the literature on the
      nature and pathology of VRS, we conclude that VRS on MR images of healthy
      individuals are normal findings, even if they are dilated. A judgement on whether
      dilated VRS in an individual patient is a normal variant or part of a disease
      process can be made by taking into account the appearance of the adjacent tissue
      on MRI and the clinical context.

PMID- 16896912
TI  - Effect of rituximab on the long-term outcome after high-dose therapy for relapsed
      B-cell non-Hodgkin's lymphoma.
AB  - To better define the role of rituximab in salvage and high-dose therapy (HDT) for
      relapsed or refractory non-Hodgkin's lymphoma (NHL), patients treated before the
      implementation of rituximab in salvage and HDT (n = 57, control group) were
      compared with patients with rituximab included in this procedure (n = 36, study
      group). All patients had been antibody-naive at this point, and analyses were
      performed separately for 22 and 31 patients with aggressive, and 14 and 26
      patients with indolent NHL, respectively. All patients received two courses of
      salvage therapy, predominantly dexamethasone, BCNU, etoposide, cytosine
      arabinoside, melphalan. Conditioning regimens included BCNU, etoposide, cytosine
      arabinoside, melphalan; BCNU, etoposide, cytosine arabinoside, cyclophosphamide
      or total body irradiation and cyclophosphamide, with rituximab added for patients
      in the study group. Despite the absence of differences in stem cell collection,
      haematopoietic recovery was delayed in patients with aggressive NHL treated in
      the study group: median days to absolute neutrophil count more than 0.5 x
      10(9)/l, 11 vs 10 (p = 0.01), and platelets more than 20 x 10(9)/l, 14 vs 11 (p =
      0.0005), with an increased requirement for platelet transfusions. No similar
      observations were made in indolent lymphoma patients. Remission rates were
      superior for patients with aggressive NHL in the study group. With a median
      follow-up of 7.25 and 4.5 years, this resulted in an improvement in OS at 4.5
      years: 67 vs 45% (95% confidence interval, 47-87% vs 28-64%; p = 0.0468). For
      patients with indolent lymphoma, no comparable benefit was detectable. Our data
      support the use of rituximab in HDT for patients with aggressive NHL. For
      patients with indolent NHL, only longer follow-up and/or randomized trials may
      help to fully determine the impact of rituximab on the outcome after HDT.

PMID- 16896913
TI  - Consensus conference on European preparedness for haematological and other
      medical management of mass radiation accidents.

PMID- 16896915
TI  - Anterior optical coherence tomography: a non-contact technique for anterior
      chamber evaluation.
AB  - PURPOSE: To assess a new non-contact anterior optical coherence tomography (OCT)
      system for anterior chamber evaluation. METHODS: A new commercial 131-nm infrared
      light anterior OCT system was used for anterior chamber evaluation. Forty-four
      eyes of 35 subjects (18 normal subjects, 17 subjects with anterior chamber
      abnormalities) were enrolled in the study. RESULTS: Eyes were divided into those
      with narrowed, broadened and normal anterior chamber depth. Anterior chamber
      angle dynamics were assessed in three patients with angle-closure glaucoma and
      cataract extraction. Anterior OCT was also used for visualization of the anterior
      chamber (OCT goniometry) in a subject with multiple local anaesthetic allergies
      with phobia regarding conventional contact gonioscopy. CONCLUSIONS: Anterior OCT
      is a new, easy-to-handle, non-contact technique that allows exact evaluation of
      anterior chamber parameters such as anterior chamber depth, chamber angle
      dynamics, corneal curvature and corneal thickness.

PMID- 16896914
TI  - T-bet expression in the iris and spleen parallels disease expression during
      endotoxin-induced uveitis.
AB  - BACKGROUND: T lymphocytes have been implicated in the development of endotoxin
      induced uveitis (EIU). T-bet is a Th1 cell-specific transcription factor that is
      involved in differentiation and effector functions. The aim of this study was to
      investigate kinetics of T-bet expression at the mRNA and protein levels during
      EIU using real-time PCR and whole-mount immunohistochemistry. METHODS: A single
      footpad injection of 200 mug of lipopolysaccharide (LPS) was administered to male
      Wistar rats in order to induce EIU. Clinical changes were followed by slit-lamp
      examination. The expression of T-bet mRNA in the spleen was evaluated 0, 8, 16,
      24, 48, and 96 h after LPS injection using real-time PCR. Immunohistochemistry
      was performed on the iris whole-mounts as well as on frozen sections of the
      spleen to evaluate T-bet protein expression. Terminal deoxynucleotidyl
      transferase dUTP nick end labeling (TUNEL) was performed on the iris whole-mounts
      to assay apoptotic cells. RESULTS: Uveitis was observed in all rats that received
      LPS. T-bet(+) cells and TUNEL(+) cells in the iris whole-mounts showed a similar
      pattern in cell number and distribution and both types of cells were observed at
      8 h, significantly increased 24 h, and decreased 48 h after LPS injection. T-bet
      expression at both the mRNA and protein levels in spleen also paralleled ocular
      inflammation. It was weakly detectable after 0 h, increased after 8 h (index 1.3,
      T-bet(+) cells OD 17.43+/-2.15), reached its peak after 24 h (index 4.00, OD
      53.52+/-4.00), and decreased 48 h following LPS injection (index 1.38, OD 25.75+/
      2.45). CONCLUSIONS: The results show that T-bet expression in both the iris and
      the spleen, and in apoptotic cells in the iris parallel the severity of
      intraocular inflammation after systemic LPS administration. These results suggest
      that T-bet may play a significant role in the dynamics of EIU.

PMID- 16896916
TI  - Transplantation of bone marrow-derived mesenchymal stem cells rescue
      photoreceptor cells in the dystrophic retina of the rhodopsin knockout mouse.
AB  - BACKGROUND: Retinitis pigmentosa belongs to a large group of degenerative
      diseases of the retina with a hereditary background. It involves loss of retinal
      photoreceptor cells and consequently peripheral vision. At present there are no
      satisfactory therapeutic options for this disease. Just recently the use of
      mesenchymal stem cells has been discussed as one therapeutical option for retinal
      degeneration, as they have been shown to differentiate into various cell types,
      including photoreceptor cells. In this article we wanted to investigate the
      potency of mesenchymal stem cells to induce rescue effects in an animal model for
      retinitis pigmentosa, the rhodopsin knockout mouse. METHODS: For the experiments,
      three experimental groups of 10 animals each were formed. The first group
      consisted of untreated rhodopsin knockout (rho(-/-)) animals used as controls.
      The second group consisted of rho(-/-) mice that had received an injection of
      mouse mesenchymal stem cells, which were transduced using an adenoviral vector
      containing the sequence for the green fluorescent protein (GFP) prior to
      transplantation. In the third sham group, animals received an injection of medium
      only. Thirty-five days after transplantation, GFP-expressing cells were detected
      in whole-mount preparations of the retinas as well as in cryostat sections. For
      the detection of rescue effects, semi-thin sections of eyes derived from all
      experimental groups were produced. Furthermore, rescue effects were also analysed
      ultrastructurally in ultrathin sections. RESULTS: Histological analysis revealed
      that after transplantation, cells morphologically integrated not only into the
      retinal pigment epithelium but also into layers of the neuroretina displaying
      neuronal and glial morphologies. Furthermore, significant rescue effects, as
      demonstrated by the occurrence of preserved photoreceptor cells, were detected.
      CONCLUSIONS: Our data indicate that mesenchymal stem cells can prolong
      photoreceptor survival in the rhodopsin knockout mouse, also providing evidence
      of a therapeutical benefit in retinitis pigmentosa.

PMID- 16896917
TI  - Measurement of autofluorescence in the parapapillary atrophic zone in patients
      with ocular hypertension.
AB  - PURPOSE: The purpose of the study was to investigate area and intensity of
      parapapillary autofluorescence in patients with ocular hypertension and controls.
      PATIENTS AND METHODS: Forty-two consecutive patients with ocular hypertension and
      25 controls were investigated in a controlled prospective cross-sectional trial.
      All patients and controls were members of the Erlangen Glaucoma registry and
      received complete ophthalmologic examination and detailed standardized glaucoma
      examination, including 24-h IOP measurement, perimetrie (G1, three phases) and 15
      degrees stereographic slides of the optic disc. Additionally, patients and
      controls were investigated with VEP with blue on yellow pattern stimulation and
      confocal scanning laser ophthalmoscope (HRA II, Heidelberg Engineering,
      Dossenheim, Germany) to detect lipofuscin in the parapapillary atrophic zone.
      Eyes with retinal diseases or pathologic changes of retinal pigmentepithelium
      were excluded. Extension of parapapillary area with increased autofluorescence
      compared (qualitatively) to background autofluorescence around the optic disc and
      the level of autofluorescence (quantitatively) in the area of qualitatively
      increased autofluorescence was measured. Patients and controls did not differ
      significantly concerning age. RESULTS: The area of parapapillary autofluorescence
      was significant larger in patients with ocular hypertension than in the control
      group (0.21+/-0.17 mm(2) versus 0.07+/-0.06 mm(2); P<0.001, Mann-Whitney U-test).
      An increased latency of blue-on-yellow pattern VEP was seen in patients with OHT
      with increasing parapapillary autofluorescence area (r=0.496; P<0.001, Spearman
      Rho test). CONCLUSION: Parapapillary autofluorescence is increased in patients
      with ocular hypertension. Patients with large area of parapapillary
      autofluorescence had also an increased latency in blue on yellow pattern VEP.

PMID- 16896918
TI  - Prospective optical coherence tomographic evaluation of the efficacy of oral and
      posterior subtenon corticosteroids in patients with intermediate uveitis.
AB  - PURPOSE: To prospectively evaluate the efficacy of oral corticosteroids and
      posterior subtenon injection in the treatment of macular edema in patients with
      intermediate uveitis using optical coherence tomography (OCT). METHODS: Twenty
      two patients with intermediate uveitis were treated with posterior subtenon
      injection when the disease was unilateral (group A, n=11) or with oral steroids
      when the disease was bilateral (group B, n=11). Changes in macular thickness from
      baseline was determined using OCT in both groups at day 0, day 3, day 14, 6 weeks
      and 12 weeks. RESULTS: Statistically significant improvement in Snellen visual
      acuity in group A was seen at 6 weeks and in group B at 2 weeks. In patients
      receiving oral corticosteroids, foveal thickness decreased by 63% by day 3. In
      those treated with posterior subtenon injection, even at day 14 only a 55%
      reduction of foveal thickness was evident. Spearman's correlation coefficient for
      visual acuity and foveal thickness was found to be significant. CONCLUSION: OCT
      confirms a significantly more rapid decrease in macular edema in patients treated
      with oral corticosteroids. A short course of oral steroids may be useful in
      enabling earlier visual recovery in patients treated with posterior subtenon
      injection for unilateral uveitic macular edema.

PMID- 16896920
TI  - Chorioretinal folds as a consequence of inferior staphyloma associated with
      tilted disc syndrome.
AB  - BACKGROUND: Tilted disc syndrome is a common condition which is usually
      associated with an inferior staphyloma. MATERIALS AND METHODS: Observational case
      report. RESULTS: An 82-year-old woman presented with features typical of tilted
      disc syndrome, as well as chorioretinal folds orientated radially to the upper
      edge of the inferior staphyloma. CONCLUSION: The orientation of the folds
      suggested that the progressive increase of the inferior staphyloma exerted
      traction on the RPE, Bruch's membrane and choriocapillaris complex, leading to
      chorioretinal folds radiating from the upper edge of the staphyloma.

PMID- 16896919
TI  - Accumulation of A2-E in mitochondrial membranes of cultured RPE cells.
AB  - BACKGROUND: Lipofuscin occurs in association with various blinding diseases,
      including ARMD. Formation of lipofuscin is considered to be initiated by the
      inability of the RPE lysosome to degrade constituents of phagocytosed material
      resulting in its intralysosomal accumulation. Thus, the deposition of abnormal
      retinoid adducts causing the autofluorescent properties of RPE lipofuscin
      originates from abnormal products of the retinoid cycle contained in phagocytosed
      photoreceptor outer segments. The major lipofuscin retinoid conjugate A2-E was
      previously shown to exert toxic effects on RPE cells by directly damaging
      lysosomal function and structure. However, A2-E was also proposed to severely
      harm extralysosomal RPE cell structures during the pathogenesis of ARMD. This
      would require release or leakage of A2-E from the lysosomal compartment with
      subsequent targeting of other cellular compartments. METHODS: We therefore now
      investigated intralysosomal accumulation, possible biodegradation, release from
      the lysosomal compartment and intracellular spreading of (14)C-labelled A2-E in
      cultured human RPE cells. We specifically loaded lysosomes of cultured human RPE
      cells with [(14)C]A2-E. RESULTS: A linear increase of intracellular radioactivity
      was observed during the 4-week loading period. Cell fractionation experiments
      indicated that more than 90% of loaded A2-E was specifically accumulating in the
      lysosomes. After loading, the fate of the radioactive label was chased over a
      period of an additional 4 weeks. No metabolism or secretion of A2-E to the medium
      was detectable. Subcellular fractionation revealed that during the chase period,
      about 13% were shifted from the lysosomes to mitochondrial fractions. This effect
      was strikingly intensified when after loading the cells with the labeled
      retinoid, its intralysosomal concentration was boosted by an additional load with
      non-labeled A2-E. Thus about 44% of the label were located in mitochondria at the
      end of the chase period. No significant spreading to other cell compartments was
      detectable. CONCLUSIONS: Since A2-E was suggested to act as a proapoptotic
      molecule via a mitochondrial pathway, we postulate that upon reaching a critical
      intralysosomal concentration, A2-E is released from the lysosome and then
      specifically targets the outer mitochondrial membrane thereby initiating
      apoptosis of the RPE cell. This may also apply correspondingly to other
      lipofuscin-associated molecules that cause leakage of the lysosomal membrane.

PMID- 16896921
TI  - Evaluation of advanced glycation end-products in diabetic and inherited canine
      cataracts.
AB  - BACKGROUND: The receptor for advanced glycation end-products (RAGE) increases in
      the human cataract and should correlate with increased DNA damage and
      proliferation of lens epithelial cells (LECs). The purpose of this study was to
      measure and immunolocalize RAGE in normal and cataractous canine LECs, and to
      determine whether there was a correlation between RAGE and DNA damage (gadd45),
      cell-cycle regulation (p21), and LEC proliferation (proliferating cell nuclear
      antigen, PCNA). METHODS: Thirty-two anterior lens capsules from 22 dogs that
      underwent cataract surgery and 10 lenses from dogs with normal eyes were
      evaluated. Eleven of the cataractous lenses were from diabetic patients (n=16),
      and eleven were from patients with inherited cataracts (n=16). Standard
      immunohistochemical staining was performed using antibodies against RAGE, gadd45,
      p21, PCNA, alpha-smooth muscle actin, and TGF-beta. Immunostaining intensity for
      each antibody was given a score of 0-4+. Standard Western blot analysis on normal
      and cataractous lens capsules was performed using the same antibodies as in the
      immunohistochemical staining. Comparisons were also made based on age and sex.
      Real-time reverse transcriptase-polymerase chain reaction (qRT-PCR) was performed
      for RAGE. RESULTS: There was an increase in RAGE expression with age in normal
      LECs, but no significant difference was seen when normal adult LECs were compared
      to cataractous LECs. The stage of the cataract and the presence of LIU were not
      associated with a significant increase in RAGE expression. There was no age
      dependent difference in the normal lenses for gadd45, p21, or PCNA. Significant
      up-regulation of p21 (P < 0.05) and PCNA (P < 0.05) was seen in diabetic
      cataracts compared to inherited cataracts. CONCLUSION: RAGE and PCNA expression
      did not increase with cataractogenesis, possibly due to overexpression associated
      with normal aging and constant exposure to oxidative stress from sunlight-related
      ultraviolet irradiation, respectively. However, p21 and PCNA increased in
      diabetic cataractogenesis suggesting cell cycle and proliferation dysregulation.
      This may be related to the rapid onset in this type of cataract compared with the
      more chronic and slower-to-develop inherited cataracts.

PMID- 16896922
TI  - Clinical and molecular genetic features of ARC syndrome.
AB  - Arthrogryposis, renal dysfunction and cholestasis (ARC) syndrome (MIM 208085) is
      an autosomal recessive multisystem disorder that may be associated with germline
      VPS33B mutations. VPS33B is involved in regulation of vesicular membrane fusion
      by interacting with SNARE proteins, and evidence of abnormal polarised membrane
      protein trafficking has been reported in ARC patients. We characterised clinical
      and molecular features of ARC syndrome in order to identify potential genotype
      phenotype correlations. The clinical phenotype of 62 ARC syndrome patients was
      analysed. In addition to classical features described previously, all patients
      had severe failure to thrive, which was not adequately explained by the degree of
      liver disease and 10% had structural cardiac defects. Almost half of the patients
      who underwent diagnostic organ biopsy (7/16) developed life-threatening
      haemorrhage. We found that most patients (9/11) who suffered severe haemorrhage
      (7 post biopsy and 4 spontaneous) had normal platelet count and morphology.
      Germline VPS33B mutations were detected in 28/35 families (48/62 individuals)
      with ARC syndrome. Several mutations were restricted to specific ethnic groups.
      Thus p.Arg438X mutation was common in the UK Pakistani families and haplotyping
      was consistent with a founder mutation with the most recent common ancestor 900
      1,000 years ago. Heterozygosity was found in the VPS33B locus in some cases of
      ARC providing the first evidence of a possible second ARC syndrome gene. In
      conclusion we state that molecular diagnosis is possible for most children in
      whom ARC syndrome is suspected and VPS33B mutation analysis should replace organ
      biopsy as a first line diagnostic test for ARC syndrome.

PMID- 16896923
TI  - Identification and characterization of a novel human dysferlin transcript:
      dysferlin_v1.
AB  - Mutations in the dysferlin (DYSF) gene are associated with limb girdle muscular
      dystrophy type 2B and Miyoshi myopathy. In this study, we report the
      identification and characterization of a novel dysferlin transcript that we named
      DYSF_v1 (GenBank accession: DQ267935). This transcript differs from the currently
      known dysferlin transcript (GenBank accession: AF075575) in the sequence of the
      entire first exon which spans 232 bases. This unique first exon is derived from
      intron 1 of DYSF, and has an immediate upstream 5' untranslated region containing
      CpG islands and sequences consistent with transcription factor binding sites.
      Exon 1 of DYSF_v1 shares 85% sequence homology and has similar genomic
      organization with the first exon of mouse dysferlin. Northern blot analysis
      showed that the DYSF_v1 transcript spans 7.5 kb and is expressed in human
      skeletal muscle, heart, placenta, brain, spleen, kidney, intestine, and lung
      tissues. DYSF_v1 retains phylogenic conservancy and shows similar expression
      pattern as the currently known human dysferlin.

PMID- 16896924
TI  - A classical likelihood based approach for admixture mapping using EM algorithm.
AB  - Several disease-mapping methods have been proposed recently, which use the
      information generated by recent admixture of populations from historically
      distinct geographic origins. These methods include both classic likelihood and
      Bayesian approaches. In this study we directly maximize the likelihood function
      from the hidden Markov Model for admixture mapping using the EM algorithm,
      allowing for uncertainty in model parameters, such as the allele frequencies in
      the parental populations. We determined the robustness of the proposed method by
      examining the ancestral allele frequency estimate and individual marker-location
      specific ancestry when the data were generated by different population admixture
      models and no learning sample was used. The proposed method outperforms a widely
      used Bayesian MCMC strategy for data generated from various population admixture
      models. The multipoint information content for ancestry was derived based on the
      map provided by Smith et al. (2004) and the associated statistical power was
      calculated. We examined the distribution of admixture LD across the genome for
      both real and simulated data and established a threshold for genome wide
      significance applicable to admixture mapping studies. The software ADMIXPROGRAM
      for performing admixture mapping is available from authors.

PMID- 16896925
TI  - Genetic characterization and fine mapping of susceptibility loci for sarcoidosis
      in African Americans on chromosome 5.
AB  - Sarcoidosis, a systemic granulomatous disease, likely results from both
      environmental agents and genetic susceptibility. Sarcoidosis is more prevalent in
      women and, in the United States, African Americans are both more commonly and
      more severely affected than Caucasians. We report a follow up of the first genome
      scan for sarcoidosis susceptibility genes in African Americans. Both the genome
      scan and the present study comprise 229 African American nuclear families
      ascertained through two or more sibs with sarcoidosis. Regions studied included
      those which reached a significance in the genome scan of 0.01 (2p25, 5q11, 5q35,
      9q34, 11p15 and 20q13), 0.05 (3p25 and 5p15-13) or which replicated previous
      findings (3p14-11). We performed genotyping with additional markers in the same
      families used in the genome scan. We examined multi-locus models for epistasis
      and performed model-based linkage analysis on subsets of the most linked families
      to characterize the underlying genetic model. The strongest signal was at marker
      D5S407 (P=0.005) on 5q11.2, using both full and half sibling pairs. Our results
      support, in an African American population, a sarcoidosis susceptibility gene on
      chromosome 5q11.2, and a gene protective for sarcoidosis on 5p15.2. These fine
      mapping results further prioritize the importance of candidate regions on
      chromosomes 2p25, 3p25, 5q35, 9q34, 11p15 and 20q13 for African Americans.
      Additionally, our results suggest joint action of the effects of putative genes
      on chromosome 3p14-11 and 5p15.2. We conclude that multiple susceptibility loci
      for sarcoidosis exist in African Americans and that some may have interdependent
      effects on disease pathogenesis.

PMID- 16896926
TI  - The association of DNA sequence variation at the MAOA genetic locus with
      quantitative behavioural traits in normal males.
AB  - Monoamine oxidase A (MAOA) catalyses the oxidative deamination of biogenic amines
      including neurotransmitters, mainly norepinephrine and serotonin in the brain and
      peripheral tissues. A nonsense mutation in the gene was shown to be involved in a
      rare X-linked behavioural syndrome, which includes impaired impulse control,
      aggression and borderline mental retardation (Brunner syndrome). Several recent
      studies have shown the association of genetic variation of a VNTR in the gene
      promoter with various pathological behavioural traits. In the present study the
      association of MAOA genetic variation with a large set of quantitative
      behavioural traits in normal individuals has been examined. DNA samples from 421
      unrelated males were genotyped for 14 SNPs and for the promoter VNTR at the MAOA
      locus. An additional 16 SNPs were genotyped at apparently neutral loci across the
      X chromosome to serve as a genomic control for possible false positive
      associations due to population structure. Behavioural traits were measured using
      the NEO psychometric questionnaire, which is based on a 5-axis model of
      personality, and consists of 30 different quantitative traits. There was a robust
      association of the A2 ("straightforwardness") facet with common allelic variants
      at the promoter VNTR. Most of the tested traits were not associated with the VNTR
      despite reasonable power, thus demonstrating that the VNTR influence on
      quantitative behavioural traits in normal males may be very specific. In
      contrast, several traits of the C ("conscientiousness") axis were associated with
      less common SNP-defined haplotypes. Hence, it appears that common genetic
      variation at the VNTR contributes to the behavioural attribute of
      "straightforwardness", while rare haplotypes defined by SNPs downstream of the
      transcription start site may contribute to "conscientiousness". This study is
      used to address the validation, interpretation and limitation of genetic
      association studies of quantitative behavioural traits.

PMID- 16896928
TI  - Clinical evaluation of chemosensitivity testing for patients with unresectable
      non-small cell lung cancer (NSCLC) using collagen gel droplet embedded culture
      drug sensitivity test (CD-DST).
AB  - PURPOSE: In the present study, we prospectively evaluated the clinical
      feasibility and efficacy of collagen gel droplet embedded culture drug
      sensitivity test (CD-DST) in unresectable non-small cell lung cancer (NSCLC)
      without previous treatment. EXPERIMENTAL DESIGN: Eighty patients with
      unresectable NSCLC, aged less than 81 years old, PS 0-1, and with evaluable tumor
      lesions, entered the study. If the patient had CD-DST active drugs, more than
      three cycles of chemotherapy containing these drugs were administered. If the
      patient did not have CD-DST active drugs, the patient could choose any treatment
      including best supportive care. RESULTS: Of the 80 patients in this study, CD-DST
      yielded results successfully in 49 patients (61.3%). CD-DST active drugs were
      present in 22 patients, and significantly more female patients had in vitro
      active anticancer agents than male (P=0.0008). All of the patients with CD-DST
      active agents received chemotherapy including these agents. In these patients,
      the response rate was 72.7%, and median survival was 15.0 months. In the patients
      without CD-DST active agents, 11 patients received standard, empirical
      chemotherapy. In these patients, response rate was 0%, and median survival was
      6.0 months. CONCLUSIONS: The results show that CD-DST is capable of selecting the
      responders and the respective optimal regimens, and also delineating the patients
      less likely benefit from treatment.

PMID- 16896927
TI  - A molecular mechanism for the differential regulation of TGF-beta1 expression due
      to the common SNP -509C-T (c. -1347C > T).
AB  - Transforming growth factor beta1 (TGF-beta1) levels influence many cellular,
      immunologic and pathologic processes. Activator protein 1 (AP1) and hypoxia are
      key regulators of TGF-beta1 expression levels. The common TGFB1 promoter SNP c.
      1347C > T (-509C-T, rs1800469) has been linked to a nearly twofold difference in
      plasma levels among individuals and with risk, progression, and outcome of
      numerous diseases. We demonstrate exclusive in vitro and in vivo recruitment of
      AP1 containing JunD to -1347C. This study also is the first to demonstrate
      hypoxia inducible factor 1 (HIF-1) binding to the TGFB1 promoter. HIF-1 was found
      to associate with both -1347C and -1347T and compete with AP1 for binding to 
      1347C. Reporter constructs demonstrate that expression differences between -1347C
      and -1347T are due to selective AP1 recruitment to the TGFB1 promoter. As AP1 is
      known to down-regulate transcription of other genes, we suggest that the
      molecular mechanism for the difference in TGF-beta1 plasma levels linked to -1347
      is due to transcriptional suppression by AP1 binding to -1347C. These data should
      aid in our understanding of the association of the -1347 SNP with the
      pathogenesis of certain TGF-beta1-related diseases.

PMID- 16896930
TI  - A phase I trial of intermittent high-dose gefitinib and fixed-dose docetaxel in
      patients with advanced solid tumors.
AB  - PURPOSE: Based on our mouse xenograft model demonstrating that intermittent high
      dose gefitinib sensitizes tumors to subsequent treatment with taxanes, we
      initiated this phase I trial to explore docetaxel in combination with escalating
      doses of intermittent gefitinib (Iressa) given prior to docetaxel. METHODS: This
      was a phase I study where patients with advanced cancer were treated with
      escalating doses of gefitinib (1,000, 1,500, 2,250, 3,000 mg) on days 1 and 2
      followed by docetaxel (75 mg/m2) on day 3 of a 21 day cycle. Gefitinib
      pharmacokinetic data were obtained on days 1, 2, and 3 of cycles 1 and 2 at each
      dose level. RESULTS: 18 patients were enrolled in this study with the most
      frequent tumor types being non-small cell lung cancer and head and neck squamous
      cell cancer. The dose-limiting toxicity was neutropenia (n=1 at dose level 2, n=2
      at dose level 4). Rash, diarrhea, and fatigue were the most common grade 1-2
      toxicities. Pharmacokinetic data indicated no accumulation of gefitinib between
      cycles 1 and 2 and no clear correlation between gefitinib plasma levels and
      toxicity. Partial responses were observed in one patient with head and neck
      squamous cell carcinoma and one patient with anaplastic thyroid cancer.
      CONCLUSION: The recommended dose for phase II studies is gefitinib 2,250 mg on
      days 1 and 2, followed by docetaxel 75 mg/m2 on day 3.

PMID- 16896929
TI  - Reproductive toxicity evaluation of a new camptothecin anticancer agent, CKD-602,
      in pregnant/lactating female rats and their offspring.
AB  - CKD-602 is a camptothecin anticancer agent that was recently developed by the
      Chong Kun Dang Pharmaceutical Co. (Seoul, Korea). This study examined the
      potential adverse effects of CKD-602 on pregnancy, delivery, and lactation in
      female Sprague-Dawley rats as well as on the pre- and postnatal development of
      their offspring. One hundred pregnant females were divided into four groups:
      three treatment groups and a control group. CKD-602 was administered once daily
      by intravenous bolus injection to female rats at doses of 0, 5.7, 17, or 51
      microg/kg/day from gestational day 6, through to parturition and throughout the
      period of lactation up to weaning [lactational day (LD) 21]. All the dams were
      sacrificed on LD 22 after weaning. The clinical signs, mortality, body weight
      change, food consumption, physical development, and behavioral function were
      evaluated in their progeny. When the exposed offspring reached maturity
      (postnatal day 70), their reproductive performance was assessed. In the high-dose
      group, suppressed body weight and a decrease in the amount of food consumption
      were observed in the dams during both the gestation and lactation periods. An
      increase in the incidence of thymic atrophy, decreased liver and ovary weight,
      and an increase in the weight of the spleen were also observed in the dams at the
      scheduled necropsy. In addition, an increase in the number of stillborn and
      postnatal mortality, a decrease in the live litter size, and a delay in physical
      development were observed in the F1 offspring. Teratological examinations showed
      an increase in the incidence of congenital anomalies in both the F1 offspring and
      F2 fetuses. In the medium dose group, only slight maternal toxicity including
      suppressed body weight and decreased food consumption was observed. There were no
      treatment-related effects on the maternal function and pre- and postnatal
      development in the low dose group. The no-observed-adverse-effect level (NOAEL)
      of CKD-602 for the dams are considered to be 5.7 microg/kg/day, however, the
      NOAEL for their offspring are estimated to be 17 microg/kg/day.

PMID- 16896931
TI  - Androgen and c-Kit receptors in desmoplastic small round cell tumors resistant to
      chemotherapy: novel targets for therapy.
AB  - PURPOSE: Desmoplastic small round cell tumor (DSRCT) is a highly fatal, mainly
      peritoneal cell origin cancer which predominantly affects young adult males. This
      predilection in young males led us to examine the role of androgen receptors
      (AR), testosterone, and growth factors in the biology of DSRCT. METHODS: Slides
      were prepared from 27 multi-institutional patients all with end-stage DSRCT.
      Slides were stained for AR, c-Kit, various growth factors, and drug resistance
      associated proteins. Immunohistochemical (IHC) expression was scored semi
      quantitatively. Western blot and MTT studies were performed to validate the IHC
      findings of over-expression of the AR and its functional status by stimulation of
      growth by dihydrotestosterone, respectively. Six patients with positive AR status
      were treated solely with combined androgen blockade (CAB) as used for prostate
      cancer. RESULTS: Twenty-two patients were male (81%) and five were female (19%)
      with a median age at diagnosis of 23. All patients had failed at least two prior
      multi-agent chemotherapy regimens and 44% had progressed after autologous stem
      cell transplant. DSRCT samples from 10 of 27 patients were >or=2+ IHC positive
      for AR (37%,P=0.0045) and 7 of 20 patients were >or=2+ IHC positive for c-Kit
      (35%, P=0.018). We found elevated IHC expression of GST-pi, MRP and thymidylate
      synthase in smaller subsets of patients. In vitro studies for AR by Western blot
      and stimulation of growth by dihydrotestosterone in MTT assays suggest that the
      AR in DSRCT cells is functional. Six patients with positive AR status were
      treated with CAB alone and three of six attained clinical benefit (1-PR, 1-MR, 1
      SD) in a range of 3-4 months. The three patients who responded to CAB had normal
      testosterone levels before CAB, while the three who did not respond to CAB had
      baseline castrate levels of testosterone. CONCLUSIONS: DSRCT has significant IHC
      expression of AR and c-Kit in heavily pre-treated patients. The presence of
      significant AR expression in 37% suggests that these patients could possibly
      respond to CAB. The significance of c-Kit expression in 35% of DSRCT patients is
      unknown and warrants further investigation.

PMID- 16896932
TI  - Improvements in glucose tolerance and insulin sensitivity after lifestyle
      intervention are related to changes in serum fatty acid profile and desaturase
      activities: the SLIM study.
AB  - AIMS/HYPOTHESIS: The aim of this study was to investigate whether lifestyle
      intervention-induced changes in serum fatty acid profile of cholesteryl esters
      and estimated desaturase activities are related to improvements in insulin
      sensitivity in subjects at risk of type 2 diabetes. MATERIALS AND METHODS: In the
      Study on Lifestyle Intervention and Impaired Glucose Tolerance Maastricht (SLIM),
      97 men and women with IGT were randomised to a combined diet and exercise
      programme (47 intervention) or a control group (50 control subjects). At baseline
      and after 1 year the following assessments were made: an OGTT, an exercise test
      to determine maximal aerobic capacity, anthropometry, and analysis of the serum
      fatty acid profile of cholesteryl esters. RESULTS: The lifestyle programme was
      effective in reducing the intake of total and saturated fat, increasing physical
      activity, reducing obesity and improving insulin sensitivity and glucose
      tolerance. Regression analysis of the total population showed that an increase in
      the C20:4 n-6/C20:3 n-6 ratio (estimated Delta5-desaturase activity) and
      reductions in the C18:3 n-6/C18:2 n-6 ratio (estimated Delta6-desaturase
      activity) and the C16:1 n-7/C16:0 ratio (estimated Delta9-desaturase activity or
      stearoyl-CoA desaturase-1) were significantly associated with a decrease in
      homeostasis model assessment for insulin resistance. After adjustment for
      lifestyle changes (change in percentage body fat, aerobic capacity and saturated
      fat intake), these associations were partly reduced, but remained statistically
      significant. CONCLUSIONS/INTERPRETATION: Lifestyle-induced changes in fatty acid
      profile of cholesteryl esters and desaturase activities were independently
      related to changes in insulin sensitivity in subjects at risk of type 2 diabetes.

PMID- 16896933
TI  - Impact of parental smoking on diabetes, hypertension and the metabolic syndrome
      in adult men and women in the San Antonio Heart Study.
AB  - AIMS/HYPOTHESIS: In the San Antonio Heart Study (SAHS) we investigated the
      effects of exposure to parental smoking on diabetes, hypertension and the
      metabolic syndrome in adult offspring aged 25-64 years. SUBJECTS, MATERIALS AND
      METHODS: In a retrospective cohort study the parental smoking status during
      childhood, obtained through a postal questionnaire, determined a person's
      exposure status. Logistic regression models were used to calculate odds ratios
      for diabetes, hypertension and the metabolic syndrome at the baseline SAHS
      examination in relation to parental smoking status. All models were adjusted for
      age, sex, ethnicity, education years, personal smoking status (current, former or
      never-smoker), BMI and, in the case of diabetes, a family history of diabetes.
      RESULTS: Of the 2,371 participants who returned the mailing, 44.5, 5.4, 20.0 and
      30.1% reported that their father, mother, both or neither parent smoked,
      respectively. Participants reporting that both parents smoked were 1.60 (95% CI:
      0.95-2.69) times more likely to have diabetes, 1.55 (95% CI: 1.05-2.28) times
      more likely to have hypertension, and 1.46 (95% CI: 1.01-2.10) times more likely
      to have the metabolic syndrome than participants reporting that neither parent
      smoked during their childhood. Odds ratios, after limiting the population to
      younger participants (i.e. <or=50 years) to reduce survivor bias, were 2.53 (95%
      CI: 1.21-5.31), 1.29 (95% CI: 0.78-2.16), and 1.41 (95% CI: 0.89-2.22) for
      diabetes, hypertension and the metabolic syndrome, respectively.
      CONCLUSIONS/INTERPRETATION: These results provide evidence that early exposure to
      parental smoking may be associated with an increased risk of diabetes and perhaps
      hypertension and the metabolic syndrome.

PMID- 16896934
TI  - The effect of diabetes and stroke at baseline and during follow-up on stroke
      mortality.
AB  - AIMS/HYPOTHESIS: The aim of this study was to compare the magnitude of the effect
      of diabetes and stroke at baseline and during follow-up on risk of stroke
      mortality. MATERIALS AND METHODS: Study cohorts included 25,155 Finnish men and
      26,423 women aged 25-74 years. Data on diabetes and stroke history at baseline,
      their incidence during follow-up, and stroke death were obtained from national
      registers. RESULTS: During a mean follow-up of 18.9 years, 838 stroke deaths were
      recorded. In the baseline study, hazard ratios (HRs) for stroke mortality were
      5.26 for men with prior diabetes only, 4.76 for men with prior stroke only, and
      13.4 for men with both prior diabetes and stroke compared with men without
      diabetes and stroke at baseline and during follow-up. In women, the corresponding
      hazard ratios were 7.29, 5.27 and 5.52, respectively. When only diabetes and
      stroke status during the follow-up were considered, the hazard ratios for stroke
      mortality were 1.41 for men and 1.56 for women with incident diabetes only, 5.62
      for men and 5.58 for women with incident stroke only, and 5.59 for men and 4.48
      for women with both incident diabetes and stroke compared with men and women
      without diabetes and stroke at baseline and during follow-up.
      CONCLUSIONS/INTERPRETATION: Diabetes and stroke, present either at baseline or
      during follow-up, markedly increase the risk of stroke death. Prior stroke at
      baseline carries a similar risk of stroke mortality as prior diabetes. There is a
      greater risk of stroke mortality associated with incident stroke during follow-up
      than with incident diabetes.

PMID- 16896935
TI  - High glucose and homocysteine synergistically affect the metalloproteinases
      tissue inhibitors of metalloproteinases pattern, but not TGFB expression, in
      human fibroblasts.
AB  - AIMS/HYPOTHESIS: Atherosclerosis is particularly aggressive in patients with
      diabetes. Hyperhomocysteinaemia causes oxidative stress and cytokine secretion:
      its atherogenic effect is mediated by an enhanced inflammatory response. Matrix
      metalloproteinases (MMPs) regulate extracellular matrix degradation and
      remodelling, and contribute to the vulnerability of the atherosclerotic lesion.
      Fibroblasts contribute to collagen biosynthesis and participate in plaque
      remodelling via expression and release of MMP2 and MMP9. To explore the role of
      hyperhomocysteinaemia in cellular pathways involved in plaque growth and
      stability in diabetic patients, we studied the effect of hyperhomocysteinaemia in
      human fibroblasts grown in the presence of normal or high glucose concentrations.
      MATERIALS AND METHODS: In fibroblasts of five normal subjects, grown at 5.5 or 22
      mmol/l glucose and treated with homocysteine, we determined: (1) MMP2, MMP9 and
      tissue inhibitor of metalloproteinases (TIMP)-1 (an MMP inhibitor) production by
      western blot analysis; (2) their activity by zymography; (3) TGFB1 expression by
      real-time PCR; and (4) TGFB, fibronectin and IL6 release by ELISA. RESULTS:
      Hyperhomocysteinaemia increased the production and enzymatic activity of MMP2 and
      MMP9, the effect being more pronounced in high glucose. Conversely, TIMP1
      production was reduced by hyperhomocysteinaemia in both conditions, especially in
      high glucose. Hyperhomocysteinaemia also stimulated IL6 release, at least in part
      through nuclear factor-kappaB activation. TGFB1 expression was not affected by
      hyperhomocysteinaemia either in normal or in high glucose.
      CONCLUSIONS/INTERPRETATION: Homocysteine upregulates the MMP-TIMP pathway and IL6
      release, the effect being stronger in the presence of high glucose. These actions
      of homocysteine may contribute to the increased atherogenesis observed in
      diabetic patients with poor metabolic control.

PMID- 16896936
TI  - The impact of the mTOR inhibitor sirolimus on the proliferation and function of
      pancreatic islets and ductal cells.
AB  - AIMS/HYPOTHESIS: The Edmonton Protocol for islet transplantation has provided
      hope for type 1 diabetic patients. However, this protocol requires lifelong
      immunosuppression, specifically sirolimus, a cellular antiproliferate. The effect
      of sirolimus on human pancreatic ductal cells (HDCs) is not known. This may be
      important since HDCs are believed to be islet precursors. Since neonatal porcine
      islets (NPIs), which contain many ductal precursor cells, could be a potential
      clinical source of islets, we also tested the effects of sirolimus on this
      tissue. METHODS: HDCs (n=4), NPIs (n=9) and human islets (n=5) were cultured with
      and without sirolimus (20 ng/ml) for 6 days. RESULTS: HDCs and NPIs cultured with
      sirolimus showed a 50 and 28% decrease, respectively, in cell number relative to
      control (p<0.05). Control cultures expanded 1.65- and 2.44-fold relative to time
      0. Decreases in cell number of sirolimus-treated HDCs were not due to apoptosis
      as measured by TUNEL staining. No functional effects on human islets or NPIs were
      observed following static incubation with high glucose. Treatment of
      syngeneically transplanted and naive BALC/c mice with sirolimus resulted in
      altered OGTT profiles with prolonged elevation of hyperglycaemia and weight gain.
      There was no difference in graft and organ insulin content between treatment
      groups. CONCLUSIONS/INTERPRETATION: Our results indicate that sirolimus decreases
      ductal cell numbers in culture and alters glucose-stimulated insulin secretion in
      vivo. The administration of sirolimus to islet transplant recipients is likely to
      impair graft function as a result of decreasing ductal neogenesis and induction
      of insulin resistance.

PMID- 16896937
TI  - Naphthalenemethyl ester derivative of dihydroxyhydrocinnamic acid, a component of
      cinnamon, increases glucose disposal by enhancing translocation of glucose
      transporter 4.
AB  - AIMS/HYPOTHESIS: Cinnamon extracts have anti-diabetic effects. Phenolic acids,
      including hydrocinnamic acids, were identified as major components of cinnamon
      extracts. Against this background we sought to develop a new anti-diabetic
      compound using derivatives of hydroxycinnamic acids purified from cinnamon.
      METHODS: We purified hydroxycinnamic acids from cinnamon, synthesised a series of
      derivatives, and screened them for glucose transport activity in vitro. We then
      selected the compound with the highest glucose transport activity in epididymal
      adipocytes isolated from male Sprague-Dawley rats in vitro, tested it for glucose
      lowering activity in vivo, and studied the mechanisms involved. RESULTS: A
      naphthalenemethyl ester of 3,4-dihydroxyhydrocinnamic acid (DHH105) showed the
      highest glucose transport activity in vitro. Treatment of streptozotocin-induced
      diabetic C57BL/6 mice and spontaneously diabetic ob/ob mice with DHH105 decreased
      blood glucose levels to near normoglycaemia. Further studies revealed that DHH105
      increased the maximum speed of glucose transport and the translocation of glucose
      transporter 4 (GLUT4, now known as solute carrier family 2 [facilitated glucose
      transporter], member 4 [SLC2A4]) in adipocytes, resulting in increased glucose
      uptake. In addition, DHH105 enhanced phosphorylation of the insulin receptor-beta
      subunit and insulin receptor substrate-1 in adipocytes, both in vitro and in
      vivo. This resulted in the activation of phosphatidylinositol 3-kinase and
      Akt/protein kinase B, contributing to the translocation of GLUT4 to the plasma
      membrane. CONCLUSIONS/INTERPRETATION: We conclude that DHH105 lowers blood
      glucose levels through the enhancement of glucose transport, mediated by an
      increase in insulin-receptor signalling. DHH105 may be a valuable candidate for a
      new anti-diabetic drug.

PMID- 16896938
TI  - Stimulation of cAMP signalling allows isolation of clonal pancreatic precursor
      cells from adult mouse pancreas.
AB  - AIMS/HYPOTHESIS: Duct cells of the pancreas are thought to include latent
      progenitors of islet endocrine cells that can be induced to differentiate by
      appropriate morphogens. Here we developed a method for isolating pancreatic
      ductal epithelial cells from adult mice that overcomes the shortcomings of
      previous methods. MATERIALS AND METHODS: Pancreatic ductal cells were grown in
      serum-free DMEM/F12 medium in the presence of cholera toxin or 8-bromo-cyclic
      adenosine monophosphate, which is known to be an intracellular cAMP generator.
      Single cell cloning was performed by limiting dilution in serum-free medium.
      RESULTS: The isolated clonal cells expressed high levels of cytokeratin and Ipf1
      (formerly known as Pdx-1). Adenovirus-mediated expression of ngn3 (also known as
      Neurog3) and Ptf1a in these cells induced expression of insulin and somatostatin,
      and of carboxypeptidase A, respectively. Furthermore, albumin production was
      induced by dexamethasone or by long-term culture in serum-containing medium.
      CONCLUSIONS/INTERPRETATION: Stimulation of the cAMP-dependent signalling allowed
      us to isolate clonal pancreatic ductal cells from adult mice. These cells are
      able to partially differentiate into endocrine cells, exocrine cells and
      hepatocyte-like cells and are therefore considered to have the characteristics of
      endodermal progenitor cells.

PMID- 16896939
TI  - Insulin sensitisation affects lipoprotein lipase transport in type 2 diabetes:
      role of adipose tissue and skeletal muscle in response to rosiglitazone.
AB  - AIMS/HYPOTHESIS: Lipoprotein lipase (LPL) is produced by adipose tissue and
      skeletal muscle, but acts on plasma lipoproteins after being transported to
      endothelial binding sites. Insulin resistance is associated with decreased plasma
      LPL mass. We investigated the effects of insulin sensitisation on tissue-specific
      LPL expression and transport in patients with type 2 diabetes. MATERIALS AND
      METHODS: Arterio-venous gradients of plasma LPL activity and mass across adipose
      tissue and skeletal muscle were measured in 16 type 2 diabetic patients in a
      double-blind, placebo-controlled, cross-over randomised trial of rosiglitazone.
      In vivo LPL rate of action was assessed by tissue-specific arterio-venous
      triglyceride concentration gradients. LPL mRNA was quantified in adipose tissue
      and skeletal muscle biopsies. RESULTS: Adipose tissue released large quantities
      of inactive LPL (p<0.001); skeletal muscle released small amounts of active LPL
      (p<0.01). Rosiglitazone increased adipose tissue release of LPL mass (+35%,
      p=0.04) and decreased the release of active LPL from skeletal muscle (-57%,
      p=0.03). Rosiglitazone increased adipose tissue and skeletal muscle LPL mRNA, but
      did not affect adipose tissue LPL rate of action or activity. Adipose tissue
      release of LPL mass correlated with systemic LPL mass concentrations (r=0.47,
      p=0.007), suggesting that the rate of adipose tissue release of LPL mass is a
      major determinant of systemic LPL mass concentrations.
      CONCLUSIONS/INTERPRETATION: LPL transport from adipose tissue and skeletal muscle
      are regulated differently. In adipose tissue, rosiglitazone increases LPL mRNA
      abundance and LPL transport rate and possibly increases endothelial binding sites
      for LPL, but affects neither tissue LPL activity nor LPL rate of action.

PMID- 16896940
TI  - Peroxisome proliferator-activated receptor-gamma coactivator-1 and insulin
      resistance: acute effect of fatty acids.
AB  - AIMS/HYPOTHESIS: Peroxisome proliferator-activated receptor (PPAR)-gamma
      coactivator-1 (PPARGC1), a coactivator regulating the transcription of genes
      involved in oxidative metabolism, is downregulated in patients with type 2
      diabetes and in their first-degree relatives. Whether this downregulation is a
      cause or effect of early aberrations in the development of insulin resistance,
      such as disturbances in fat metabolism, is unknown. We examined whether lipid
      induced insulin resistance was associated with downregulation of expression of
      skeletal muscle genes involved in oxidative metabolism and mitochondrial
      biogenesis in humans. MATERIALS AND METHODS: Nine healthy lean male subjects
      underwent a 6-h hyperinsulinaemic-euglycaemic clamp with simultaneous infusion of
      either a lipid emulsion or glycerol as a control. Blood was sampled at regular
      time points and muscle biopsies were taken before and after every test.
      Intramuscular triacylglycerol (IMTG) content was determined by Oil Red O staining
      and gene expression was measured by quantitative PCR. RESULTS: Lipid infusion
      resulted in a approximately 2.7-fold increase in plasma NEFA levels and a 31+/-6%
      decrease in insulin sensitivity (p=0.001). The infusion of lipids resulted in a
      approximately 1.6-fold increase in IMTG (p=0.02), whereas during the clamp with
      glycerol infusion IMTG tended to decrease to approximately 53% of preinfusion
      levels (p=0.065). Lipid infusion decreased PPARGC1A, PPARGC1B and PPARA
      expression to approximately 61, 77 and approximately 52% of basal values
      respectively, whereas expression of uncoupling protein 3 was upregulated 1.8-fold
      (all p<0.05). CONCLUSIONS/INTERPRETATION: Acute elevation of plasma NEFA levels,
      leading to muscular fat accumulation and insulin resistance, downregulates
      PPARGC1A, PPARGC1B and PPARA expression, suggesting that the decrease in PPARGC1
      expression observed in the (pre)diabetic state may be the result, rather than the
      cause of lipid-induced insulin resistance.

PMID- 16896941
TI  - BCL-6: a possible missing link for anti-inflammatory PPAR-delta signalling in
      pancreatic beta cells.
AB  - AIMS/HYPOTHESIS: Inflammatory mediators contribute to pancreatic beta cell death
      in type 1 diabetes. Beta cells respond to cytokine exposure by activating gene
      networks that alter cellular metabolism, induce chemokine release (thereby
      increasing insulitis), and cause apoptosis. We have previously shown by
      microarray analysis that exposure of INS-1E cells to IL-1beta + IFN-gamma induces
      the transcription factor peroxisome proliferator-activated receptor (Ppar)-delta
      and several of its target genes. PPAR-delta controls cellular lipid metabolism
      and is a major regulator of inflammatory responses. We therefore examined the
      role of PPAR-delta in cytokine-treated beta cells. MATERIALS AND METHODS: Primary
      beta cells that had been purified by fluorescence-activated cell sorting and INS
      1E cells were cultured in the presence of the cytokines TNF-alpha, IL-1beta, or
      IL-1beta + IFN-gamma, or the synthetic PPAR-delta agonist GW501516. Gene
      expression was analysed by real-time PCR. PPAR-delta, monocyte chemoattractant
      protein (MCP-1, now known as CCL2) promoter and NF-kappaB activity were
      determined by luciferase reporter assays. RESULTS: Exposure of primary beta cells
      or INS-1E cells to cytokines induced Ppar-delta mRNA expression and PPAR-delta
      dependent CD36, lipoprotein lipase, acyl CoA synthetase and adipophilin mRNAs.
      Cytokines and the PPAR-delta agonist GW501516 also activated a PPAR-delta
      response element reporter in beta cells. Unlike immune cells, neither INS-1E nor
      beta cells expressed the transcriptional repressor B-cell lymphoma-6 (BCL-6). As
      a consequence, PPAR-delta activation by GW501516 did not decrease cytokine
      induced Mcp-1 promoter activation or mRNA expression, as reported for
      macrophages. Transient transfection with a BCL-6 expression vector markedly
      reduced Mcp-1 promoter and NF-kappaB activities in beta cells.
      CONCLUSIONS/INTERPRETATION: Cytokines activate the PPAR-delta gene network in
      beta cells. This network does not, however, regulate the pro-inflammatory
      response to cytokines because beta cells lack constitutive BCL-6 expression. This
      may render beta cells particularly susceptible to propagating inflammation in
      type 1 diabetes.

PMID- 16896942
TI  - Early diabetes-induced biochemical changes in the retina: comparison of rat and
      mouse models.
AB  - AIMS/HYPOTHESIS: Recently, various transgenic and knock-out mouse models have
      become available for studying the pathogenesis of diabetic retinopathy. At the
      same time, diabetes-induced retinal changes in the wild-type mice remain poorly
      characterised. The present study compared retinal biochemical changes in rats and
      mice with similar (6-week) durations of streptozotocin-induced diabetes.
      MATERIALS AND METHODS: The experiments were performed on Wistar rats and C57Bl6/J
      mice. Retinal glucose, sorbitol, fructose, lactate, pyruvate, glutamate, alpha
      ketoglutarate and ammonia were measured spectrofluorometrically by enzymatic
      methods. Vascular endothelial growth factor (VEGF) protein was assessed by ELISA,
      and poly(ADP-ribosyl)ation by immunohistochemistry and western blot analysis.
      Free mitochondrial and cytosolic NAD(+)/NADH ratios were calculated from the
      glutamate and lactate dehydrogenase systems. RESULTS: Retinal glucose
      concentrations were similarly increased in diabetic rats and mice, vs controls.
      Diabetic rats manifested approximately 26- and 5-fold accumulation of retinal
      sorbitol and fructose, respectively, whereas elevation of both metabolites in
      diabetic mice was quite modest. Correspondingly, diabetic rats had (1) increased
      retinal malondialdehyde plus 4-hydroxyalkenal concentrations, (2) reduced
      superoxide dismutase (SOD), glutathione peroxidase, glutathione reductase and
      glutathione transferase activities, (3) slightly increased poly(ADP-ribose)
      immunoreactivity and poly(ADP-ribosyl)ated protein abundance, and (4) VEGF
      protein overexpression. Diabetic mice lacked these changes. SOD activity was 21
      fold higher in murine than in rat retinas (the difference increased to 54-fold
      under diabetic conditions), whereas other antioxidative enzyme activities were 3-
      to 10-fold lower. With the exception of catalase, the key antioxidant defence
      enzyme activities were increased, rather than reduced, in diabetic mice. Diabetic
      rats had decreased free mitochondrial and cytosolic NAD(+)/NADH ratios,
      consistent with retinal hypoxia, whereas both ratios remained in the normal range
      in diabetic mice. CONCLUSIONS/INTERPRETATION: Mice with short-term streptozotocin
      induced diabetes lack many biochemical changes that are clearly manifest in the
      retina of streptozotocin-diabetic rats. This should be considered when selecting
      animal models for studying early retinal pathology associated with diabetes.

PMID- 16896943
TI  - Differential effects of IRS1 phosphorylated on Ser307 or Ser632 in the induction
      of insulin resistance by oxidative stress.
AB  - AIMS/HYPOTHESIS: Induction of stress kinases leading to serine
      hyperphosphorylation of IRS1 may link oxidative stress to insulin resistance. The
      aim of this study was to investigate the roles of the phosphorylated serine
      residues Ser307 and Ser632, two sites implicated in the inhibition of IRS1
      function in insulin signalling. MATERIALS AND METHODS: Fao hepatoma cells were
      exposed to an H(2)O(2)-generating system, and antibodies against the two
      phosphorylated serine residues were used for immunoprecipitation, immunoblot and
      immunofluorescence analyses. RESULTS: Exposure to approximately 50 mumol/l
      H(2)O(2) for 2 h resulted in IRS1 phosphorylation on both Ser307 and Ser632,
      concomitant with activation of inhibitor kappa kinase beta (IKKbeta) and c-Jun
      kinase (JNK). Immunoprecipitation studies revealed that the maximum overlap
      between phospho (p) Ser307-IRS1 and pSer632-IRS1 was 20%, and confocal microscopy
      suggested distinct localisations of IRS1 molecules phosphorylated on either site.
      Although pSer307-IRS1 showed decreased insulin-induced tyrosine phosphorylation
      and interaction with phosphatidylinositol 3-kinase (PI3K) in response to insulin,
      pSer632-IRS1 molecules were normally tyrosine-phosphorylated and exhibited
      typical associated PI3K activity. Salicylic acid and SP600125 partially inhibited
      IKKbeta and JNK, respectively, which indicated distinct roles for these two
      kinases in the phosphorylation of IRS1 at the two serine sites. Protection
      against oxidation-mediated impairment in insulin-induced phosphorylation of
      protein kinase B/Akt and in glycogen synthesis was achieved only by combining
      salicylic acid and SP600125. CONCLUSIONS/INTERPRETATION: These results suggest
      that pSer307-IRS1 and pSer632-IRS1 may define two minimally overlapping pools of
      IRS1 in response to oxidative stress, contributing differentially to insulin
      resistance. A combination of stress kinase inhibitors is required to protect
      against insulin resistance and IRS1 hyperphosphorylation induced by oxidative
      stress.

PMID- 16896945
TI  - Glutamatergic synapses of Drosophila neuromuscular junctions: a high-resolution
      model for the analysis of experience-dependent potentiation.
AB  - The glutamatergic synapses of developing neuromuscular junctions (NMJ) of
      Drosophila larvae are readily accessible, morphologically simple, and
      physiologically well-characterized. They therefore have a long and highly
      successful tradition as a model system for the discovery of genetic and molecular
      mechanisms of target recognition, synaptogenesis, NMJ development, and synaptic
      plasticity. However, since the development and the activity-dependent refinement
      of NMJs are concurrent processes, they cannot easily be separated by the widely
      applied genetic manipulations that mostly have chronic effects. Recent studies
      have therefore begun systematically to incorporate larval foraging behavior into
      the physiological and genetic analysis of NMJ function in order to analyze
      potential experience-dependent changes of glutamatergic transmission. These
      studies have revealed that recent crawling experience is a potent modulator of
      glutamatergic transmission at NMJs, because high crawling activities result after
      an initial lag-phase in several subsequent phases of experience-dependent
      synaptic potentiation. Depending on the time window of occurrence, four distinct
      phases of experience-dependent potentiation have been defined. These phases of
      potentiation can be followed from their initial induction (phase-I) up to the
      morphological consolidation (phase-III/IV) of previously established functional
      changes (phase-II). This therefore establishes, for the first time, a temporal
      hierarchy of mechanisms involved in the use-dependent modification of
      glutamatergic synapses.

PMID- 16896944
TI  - Insulin modulates the secretion of proteins from mature 3T3-L1 adipocytes: a role
      for transcriptional regulation of processing.
AB  - AIMS/HYPOTHESIS: Under conditions of insulin resistance and type 2 diabetes, fat
      cells are subjected to increased levels of insulin, which may have a major impact
      on the secretion of adipokines. MATERIALS AND METHODS: Using transcriptomics and
      proteomics, we investigated how insulin affects the transcription and protein
      secretion profile of mature 3T3-L1 adipocytes. RESULTS: We found that insulin has
      a significant impact on protein secretion of 3T3-L1 adipocytes. However,
      transcription is not the major regulation point for these secreted proteins. For
      extracellular matrix components, our data suggest that the mRNA level of
      processing enzymes, but not of target proteins, is the regulating point at which
      insulin stimulates secretion and function of the relevant proteins. Among these
      enzymes, we report a novel finding, namely that sulfatase 2 gene is regulated by
      insulin, which may induce a functional change in cultured adipocytes.
      CONCLUSIONS/INTERPRETATION: We propose that enhancement of protein processing and
      secretion rather than transcription of the secreted protein genes is part of the
      strategic role of insulin in the induction of cellular responses.

PMID- 16896946
TI  - Structure and function of gap junctions in the developing brain.
AB  - Gap-junction-dependent neuronal communication is widespread in the developing
      brain, and the prevalence of gap-junctional coupling is well correlated with
      specific developmental events. We summarize here our current knowledge of the
      contribution of gap junctions to brain development and propose that they carry
      out this role by taking advantage of the full complement of their functional
      properties. Thus, hemichannel activation may represent a key step in the
      initiation of Ca(2+) waves that coordinate cell cycle events during early
      prenatal neurogenesis, whereas both hemichannels and/or gap junctions may control
      the division and migration of cohorts of precursor cells during late prenatal
      neurogenesis. Finally, the recent discovery that pannexins, a novel group of
      proteins prominently expressed in the brain, are able to form both hemichannels
      and gap-junction channels suggests that we need to seek more than just connexins
      with respect to these junctions.

PMID- 16896947
TI  - Neuronal 5-HT metabotropic receptors: fine-tuning of their structure, signaling,
      and roles in synaptic modulation.
AB  - Serotonin (5-hydroxytryptamine, 5-HT) is, without doubt, the neurotransmitter for
      which the number of receptors is the highest. Fifteen genes encoding functional 5
      HT receptors have been cloned in mammalian brain. 5-HT(3) receptors are
      ionotropic receptors, whereas all the others are metabotropic G-protein-coupled
      receptors (GPCRs). 5-HT receptor diversity is further increased by post-genomic
      modifications, such as alternative splicing (up to 10 splice variants for the 5
      HT(4) receptor) or by mRNA editing in the case of 5-HT(2C) receptors. The
      cellular and behavioral implications of 5-HT(2C) receptor editing are of great
      physiological importance. Signaling of 5-HT receptors involves a great variety of
      pathways, but only some of these have been demonstrated in neurons. The classical
      view of neurotransmitter receptors localized within the synaptic cleft cannot be
      applied to 5-HT receptors, which are mostly (but not exclusively) localized at
      extra-synaptic locations either pre- or post-synaptically. 5-HT receptors are
      engaged in pre- or post-synaptic complexes composed of many GPCR-interacting
      proteins. The functions of these proteins are starting to be revealed. These
      proteins have been implicated in targeting, trafficking to or from the membrane,
      desensitization, and fine-tuning of signaling.

PMID- 16896948
TI  - Adrenoceptors and signal transduction in neurons.
AB  - The adrenergic system is an essential regulator of neuronal, endocrine,
      cardiovascular, vegetative, and metabolic functions. The endogenous
      catecholamines epinephrine and norepinephrine activate G-protein-coupled
      receptors to transmit their signal across the plasma membrane. These
      adrenoceptors can be divided into three different groups: the alpha(1)-receptors
      (alpha(1A), alpha(1B), alpha(1D)), alpha(2)-receptors (alpha(2A), alpha(2B),
      alpha(2C)), and beta-receptors (beta(1), beta(2), beta(3)). This review
      summarizes recent findings in the field of adrenoceptor signaling in neurons and
      includes a discussion of receptor-associated proteins, receptor dimerization,
      subcellular trafficking, and fluorescence optical methods for studying the
      kinetics of adrenergic signaling. Spatio-temporal imaging may become an important
      future tool for identifying the physiological significance of these complex
      signaling mechanisms in vivo. Gene-targeted mouse models carrying deletions in
      alpha(2)-adrenoceptor have provided detailed insights into specific neuronal
      functions of the three alpha(2)-receptor subtypes.

PMID- 16896949
TI  - The genetics of synapse formation and function in Caenorhabditis elegans.
AB  - The aim of this review is to introduce the reader to Caenorhabditis elegans as a
      model system, especially with respect to studies of synapse formation and
      function. We begin by giving a short description of the structure of the nervous
      system of C. elegans. As most of the findings that are reviewed here have emerged
      from studies of neuromuscular junctions (NMJs), two prominent NMJs of C. elegans
      will be outlined briefly. In addition, we summarize new findings that have added
      to our understanding of NMJs during the last few years.

PMID- 16896950
TI  - Role of AMPA receptors in synaptic plasticity.
AB  - The alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors are
      the principal molecular units for fast excitatory synaptic transmission in the
      central nervous system. The glutamate-mediated transmission efficiency of
      synaptic AMPA receptors is influenced by their subunit composition (GluR-A to
      GluR-D), post-transcriptional and post-translational modifications, the number of
      synaptic AMPA receptors, and auxiliary proteins. Functional AMPA receptors are
      located predominantly in the post-synapse but are also found at extra-synaptic
      sites and occasionally in the pre-synapse. Thus, many factors influence the tasks
      of AMPA receptors in neuronal signal transmission. At hippocampal synaptic
      connections, AMPA receptor functions have been well studied in vitro and in the
      mouse; however, it is unlikely that these observations can be generalized to all
      glutamatergic synapses in the brain.

PMID- 16896951
TI  - The calyx of Held.
AB  - The calyx of Held is a large glutamatergic synapse in the mammalian auditory
      brainstem. By using brain slice preparations, direct patch-clamp recordings can
      be made from the nerve terminal and its postsynaptic target (principal neurons of
      the medial nucleus of the trapezoid body). Over the last decade, this preparation
      has been increasingly employed to investigate basic presynaptic mechanisms of
      transmission in the central nervous system. We review here the background to this
      preparation and summarise key findings concerning voltage-gated ion channels of
      the nerve terminal and the ionic mechanisms involved in exocytosis and modulation
      of transmitter release. The accessibility of this giant terminal has also
      permitted Ca(2+)-imaging and -uncaging studies combined with electrophysiological
      recording and capacitance measurements of exocytosis. Together, these studies
      convey the panopoly of presynaptic regulatory processes underlying the regulation
      of transmitter release, its modulatory control and short-term plasticity within
      one identified synaptic terminal.

PMID- 16896952
TI  - Developmental distribution of CaM kinase II in the antennal lobe of the sphinx
      moth Manduca sexta.
AB  - The antennal lobe (primary olfactory center of insects) is completely reorganized
      during metamorphosis. This reorganization is accompanied by changing patterns of
      calcium signaling in neurons and glial cells. In the present study, we
      investigated the developmental distribution of a major calcium-dependent protein,
      viz., calcium/calmodulin-dependent protein kinase II (CaM kinase II), in the
      antennal lobe of the sphinx moth Manduca sexta by using a monoclonal antibody.
      During synaptogenesis (developmental stages 6-10), we found a redistribution of
      CaM kinase II immunoreactivity, from a homogeneous distribution in the immature
      neuropil to an accumulation in the neuropil of the glomeruli. CaM kinase II
      immunoreactivity was less intense in olfactory receptor axons of the antennal
      nerve and antennal lobe glial cells. Western blot analysis revealed a growing
      content of CaM kinase II in antennal lobe tissue throughout metamorphosis.
      Injection of the CaM kinase inhibitor KN-93 into pupae resulted in a reduced
      number of antennal lobe glial cells migrating into the neuropil to form borders
      around glomeruli. The results suggest that CaM kinase II is involved in glial
      cell migration.

PMID- 16896954
TI  - Atomoxetine occupies the norepinephrine transporter in a dose-dependent fashion:
      a PET study in nonhuman primate brain using (S,S)-[18F]FMeNER-D2.
AB  - RATIONALE: Atomoxetine is a potent and selective norepinephrine transporter (NET)
      reuptake inhibitor acting as a nonstimulant for the treatment of attention
      deficit/hyperactivity disorder (ADHD). Previous positron emission tomography
      (PET) studies had failed to demonstrate the feasibility of measuring a dose
      dependent and saturable NET occupancy in human brain using [11C]MeNER.
      OBJECTIVES: To determine if atomoxetine occupies NET in a dose-dependent fashion
      using (S,S)-[18F]FMeNER-D2 in nonhuman primate brain. METHODS: A total of eight
      PET measurements were performed in two cynomolgus monkeys. Each monkey was
      examined four times with PET: under baseline conditions and after steady-state
      infusion with 0.03, 0.06, or 0.12 mg/kg/h of atomoxetine. A prolonged intravenous
      (i.v.) infusion design was developed rather than an i.v. bolus to better mimic an
      oral absorption profile and to reach plasma steady state. RESULTS: During
      baseline conditions, (S,S)-[18F]FMeNER-D2 uptake was highest in the locus
      coeruleus, thalamus, mesencephalon, and the cingulate gyrus, whereas the
      radioactivity in the caudate was low. Peak equilibrium measurements were achieved
      using (S,S)-[18F]FMeNER-D2 in contrast to the previously reported data for
      [11C]MeNER. After administration of atomoxetine, a dose-dependent occupancy from
      38 to 82% was observed for various brain regions known to contain high densities
      of NET. CONCLUSIONS: This is the first in vivo PET study to successfully
      demonstrate the ability to measure a dose-dependent change in NET occupancy in
      brain using (S,S)-[18F]FMeNER-D2. Furthermore, an asymptotic relationship between
      N-desmethylatomoxetine plasma concentration and NET occupancy was established. In
      total, these data encourage further PET studies using (S,S)-[18F]FMeNER-D2 in
      humans.

PMID- 16896953
TI  - Dopamine receptor stimulation does not modulate the loudness dependence of the
      auditory evoked potential in humans.
AB  - RATIONALE: The Loudness Dependence of the Auditory Evoked Potential (LDAEP) has
      been suggested as a reliable measure of central serotonin function in humans;
      however, its specificity for the serotonin system remains a topic of debate, with
      possible modulation of this purported serotonin marker by other
      neurotransmitters, including dopamine. OBJECTIVES: We examined the effect of
      dopaminergic modulation on the LDAEP using the D1/D2/D3 dopamine receptor agonist
      pergolide and the D2/D3 agonist bromocriptine. METHODS: The study was a double
      blind, placebo-controlled repeated-measures design in which healthy participants
      were tested under three acute treatment conditions: placebo, bromocriptine (2.5
      mg), and pergolide (0.1 mg). Changes in the amplitude of the N1/P2 at intensities
      (60, 70, 80, 90, and 100 dB) were examined at C Z. RESULTS: Acute stimulation of
      D1/D2/D3 receptors with pergolide and D2/D3 receptors with bromocriptine in
      comparison with placebo had no effect on the LDAEP. CONCLUSION: These findings
      indicate that acute stimulation of dopamine D1, D2, and D3 receptors does not
      modulate the LDAEP in humans. Although the findings suggest that the LDAEP may
      not be modulated by acute changes in dopamine neurotransmission, further studies
      are needed to fully characterize its dopaminergic sensitivity.

PMID- 16896955
TI  - Oestrogen modulation of the effect of 8-OH-DPAT on prepulse inhibition: effects
      of aromatase deficiency and castration in mice.
AB  - OBJECTIVE: The aim of this study was to investigate the interaction of sex
      steroid hormones, particularly oestrogen, in the regulation of prepulse
      inhibition (PPI) by serotonin-1A (5-HT1A) receptors. MATERIALS AND METHODS: We
      studied aromatase knockout (ArKO) mice, which are unable to produce oestrogen but
      have high levels of testosterone, and the effects of castration. RESULTS AND
      DISCUSSION: Treatment of male ArKO mice with the 5-HT1A receptor agonist, 8
      hydroxy-dipropyl-aminotetralin (8-OH-DPAT), caused an increase in PPI that was
      significantly greater than in male wild-type controls. Castration of male mice
      caused a significant enhancement of the effect of 8-OH-DPAT in control mice;
      however, there was no change in the effect of this drug in ArKO mice. There was
      no significant effect of 8-OH-DPAT on PPI in either female ArKO or wild-type
      controls. In all experiments, the effects of 8-OH-DPAT on startle were not
      different between the groups. [3H]8-OH-DPAT autoradiography showed no differences
      in 5-HT1A receptor binding densities in areas of the forebrain, hippocampus or
      raphe region that could explain the PPI results. These data show that the absence
      of oestrogen in male ArKO mice leads to a greater effect of 5-HT1A receptor
      stimulation on PPI. This effect can be mimicked in male control mice by
      castration. The differential involvement of oestrogen and testosterone in these
      animal models is discussed.

PMID- 16896956
TI  - High-dose MDMA does not result in long-term changes in impulsivity in the rat.
AB  - RATIONALE: Evidence suggests that recreational users of (+/-)3,4
      methylenedioxymethamphetamine HCl (MDMA, "ecstasy") have cognitive and behavioral
      deficits and show increased impulsivity consistent with 5-hydroxytryptamine (5
      HT) neurotoxicity. MDMA effects on impulsivity in users are difficult to
      establish being confounded by polydrug use and individual predisposition to
      impulsivity or behavioral inhibition. OBJECTIVE: We previously observed a long
      term anxiolytic effect of a neurotoxic dose of MDMA on elevated plus maze
      behavior in Dark Agouti (DA) rats while other strains were reported to show
      anxiogenesis. We have now examined whether MDMA influences impulsivity producing
      disinhibited behavior interpretable as anxiolysis. METHODS: Impulsivity was
      measured using an operant visuospatial discrimination procedure. Male DA rats (n
      = 24) were trained to lever press for food reward in response to a light-stimulus
      and subsequently required to withhold responding. Correct responses, premature
      responses, and response latencies were used as measures of accuracy and
      impulsivity. Trained rats were administered MDMA (5 mg/kg, i.p. at 3-h intervals
      to a total of three injections). Performance was measured at 3 h and 7, 27, 49,
      and 80 days posttreatment. RESULTS: There was a short-term effect of MDMA on the
      percentage of correct responses at 3 h and day 1 with recovery to control levels
      by days 7-8 and no significant long-term changes up to day 80. There was no
      effect of MDMA on premature responses on any of the days measured. MDMA reduced
      cortical 5-HT content (MDMA 363 +/- 14 ng/g and control 440 +/- 10 ng/g tissue).
      CONCLUSION: These results suggest that impulsivity may not be directly altered by
      MDMA despite serotonergic neurotoxicity.

PMID- 16896957
TI  - C957T polymorphism of the dopamine D2 receptor gene modulates the effect of
      nicotine on working memory performance and cortical processing efficiency.
AB  - RATIONALE: In both animals and humans, nicotine produces behavioral effects that
      vary across individuals. Studies examining the role of genetic variability in
      modulating individual response to nicotine in humans have increased, with recent
      work showing that genetic variation at the dopamine D2 receptor (DRD2) predicts
      response to pharmacotherapy for tobacco dependence. OBJECTIVES: To determine
      whether a polymorphism of the DRD2 gene, C957T, that alters DRD2 binding
      availability in humans modifies the effects of nicotine on verbal working memory
      performance and on processing efficiency of brain regions that support verbal
      working memory. MATERIALS AND METHODS: Working memory and brain function were
      assessed in 36 adult subjects (15,957T allele carriers and 21,957C homozygotes),
      each of whom was studied twice, once after placement of a placebo patch and once
      after placement of a nicotine patch. Brain function was assessed using functional
      magnetic resonance imaging while the subjects performed a verbal working memory
      task. RESULTS: During performance of a task with high verbal working memory load,
      nicotine administration worsened performance accuracy and reduced the processing
      efficiency of brain regions that support phonological rehearsal during verbal
      working memory in carriers of the 957T allele. CONCLUSIONS: These findings are
      consistent with the notion that genetic variation in DRD2 contributes to
      individual variation in a range of behavioral and brain responses to nicotine in
      humans.

PMID- 16896958
TI  - The antisaccade task as an index of sustained goal activation in working memory:
      modulation by nicotine.
AB  - INTRODUCTION: The antisaccade task provides a laboratory analogue of situations
      in which execution of the correct behavioural response requires the suppression
      of a more prepotent or habitual response. Errors (failures to inhibit a reflexive
      prosaccade towards a sudden onset target) are significantly increased in patients
      with damage to the dorsolateral prefrontal cortex and patients with
      schizophrenia. Recent models of antisaccade performance suggest that errors are
      more likely to occur when the intention to initiate an antisaccade is
      insufficiently activated within working memory. Nicotine has been shown to
      enhance specific working memory processes in healthy adults. MATERIALS AND
      METHODS: We explored the effect of nicotine on antisaccade performance in a large
      sample (N = 44) of young adult smokers. Minimally abstinent participants attended
      two test sessions and were asked to smoke one of their own cigarettes between
      baseline and retest during one session only. RESULTS AND CONCLUSION: Nicotine
      reduced antisaccade errors and correct antisaccade latencies if delivered before
      optimum performance levels are achieved, suggesting that nicotine supports the
      activation of intentions in working memory during task performance. The
      implications of this research for current theoretical accounts of antisaccade
      performance, and for interpreting the increased rate of antisaccade errors found
      in some psychiatric patient groups are discussed.

PMID- 16896959
TI  - Age and sex differences in the locomotor effect of repeated methylphenidate in
      rats classified as high or low novelty responders.
AB  - RATIONALE: Rats displaying high levels of activity in an inescapable novel
      environment (high responders; HR) are more sensitive to the locomotor effect of
      stimulant drugs than rats displaying low levels of activity (low responders; LR).
      OBJECTIVE: The current study determined the age- and sex-dependent locomotor
      effects of repeated methylphenidate in HR and LR rats. MATERIALS AND METHODS:
      Periadolescent and adult male and female Sprague-Dawley rats were first
      classified as HR or LR; rats were also classified as high or low novelty seekers
      based on free-choice preference for a novel environment. Locomotor activity was
      subsequently assessed after ten daily injections of methylphenidate (3 or 10
      mg/kg s.c.) or saline. Fifteen days later, rats were challenged with saline and
      methylphenidate (10 mg/kg) over 2 days. RESULTS: During the repeated
      methylphenidate treatment phase, adult females showed greater methylphenidate
      induced hyperactivity than adult males; there was no reliable difference in
      methylphenidate-induced hyperactivity between HR and LR rats of either age or
      sex. However, periadolescent male HR rats given repeated methylphenidate showed
      greater conditioned hyperactivity after the saline challenge than periadolescent
      male LR rats. Further, adult female HR rats given repeated methylphenidate showed
      greater conditioned hyperactivity and sensitization than adult female LR rats. In
      contrast, although free-choice novelty preference was greater among
      periadolescents than adults, individual differences in this variable did not
      predict the effect of repeated methylphenidate during any phase of the
      experiment. CONCLUSION: Although individual differences in response to
      inescapable novelty predict methylphenidate-induced conditioned hyperactivity and
      sensitization, this relationship is moderated by age and sex.

PMID- 16896960
TI  - Psychopharmacologic treatment of pediatric major depressive disorder.
AB  - RATIONALE: The role of pharmacotherapy in the treatment of major depressive
      disorder (MDD) in youth has received much attention in recent years due to
      concerns of efficacy and safety of the antidepressants for the treatment of MDD
      in youth. OBJECTIVES: This review describes the existing published and
      unpublished literature regarding the efficacy and short-term safety of the
      antidepressants and decision-making process required for the use of these
      medications for youth with MDD. In addition, current continuation and maintenance
      treatments are discussed. RESULTS: In general, nine depressed youth must be
      treated with an antidepressant to obtain one clinical response above that
      achieved with placebo. To date, fluoxetine has showed the most consistent
      positive treatment effects. Depressed youth had also acutely responded to other
      antidepressants, but the response to placebo has also been high. Overall, the
      antidepressants are well tolerated, but 1-3 children and adolescents of 100
      taking antidepressants showed onset or worsening of suicidal ideation and, more
      rarely, suicide attempts. CONCLUSIONS: There is a positive risk-benefit ratio for
      the use of antidepressants in the acute treatment of depressed youth. First-line
      antidepressant treatment with-or without-specific types of psychotherapy is
      indicated for youth with MDD of at least moderate severity. All youth taking
      antidepressants must be closely monitored for suicidality and medication side
      effects. Many youth will likely require psychotherapy or additional medication
      treatments to address comorbid disorders. Treatments to prevent relapses and
      recurrences require further study.

PMID- 16896962
TI  - Midazolam does not inhibit association formation, just its storage and
      strengthening.
AB  - RATIONALE: Although there have been many studies examining the effects of
      benzodiazepines on memory performance, their effects on working memory are
      equivocal and little is known about whether they affect the efficacy of practice
      of already learned material. OBJECTIVES: The objectives in two experiments were
      to examine (a) whether midazolam impairs performance on a working memory task
      designed to minimize mnemonic strategies such as rehearsal or chunking of
      information to be recalled and (b) the effect of midazolam on repeated practice
      of paired associates that were learned before drug administration. MATERIALS AND
      METHODS: Both experiments involved subcutaneous administration of 0.03 mg of
      saline or midazolam per kilogram of bodyweight in within-subject, placebo
      controlled designs, involving 23 subjects in (a) and 31 in (b). RESULTS: The drug
      had no effect on the ability to recall the digits in serial order even though the
      encoding task prevented the digits from being rehearsed or maintained in an
      articulatory buffer. Paired associates that were learned before the injection
      showed a benefit of subsequent practice under saline but not under midazolam.
      CONCLUSIONS: The results suggest that (a) midazolam does not affect the formation
      of new associations in short-term memory provided that the presentation rate is
      not too fast to form these associations when sedated, despite the evidence that
      the drug blocks long-term memory (LTM) retention of associations; and (b) the
      potential for over-learning with practice of learned associations in LTM is
      adversely affected by midazolam such that repeated exposures do not strengthen
      new learning.

PMID- 16896963
TI  - Effects of group I metabotropic glutamate receptor antagonists on the behavioral
      sensitization to motor effects of cocaine in rats.
AB  - RATIONALE: Metabotropic glutamate receptors (mGluRs) were reported to regulate
      various behavioral effects of addictive drugs. OBJECTIVE: The present study
      evaluated the role of group I mGluRs in the progressive augmentation
      ("sensitization") of the behavioral effects observed after repeated, intermittent
      cocaine exposure. MATERIALS AND METHODS: After habituation to handling and
      baseline activity measurement (days 1-2), rats received eight injections of
      cocaine (10 mg/kg) or saline on days 3-6, 8-11, and then, were tested twice with
      acute saline and cocaine given in a counterbalanced manner on days 13 and 15.
      Before the test sessions, subjects were pretreated with mGluR1 antagonist EMQMCM
      (JNJ16567083, (3-ethyl-2-methyl-quinolin-6-yl)-(4-methoxy-cyclohexyl)-methanone
      methanesulfonate) and mGluR5 antagonist MTEP ([(2-methyl-1,3-thiazol-4
      yl)ethynyl]pyridine). RESULTS: Pretreatment with EMQMCM (2.5-10 mg/kg) but not
      MTEP (2.5-10 mg/kg) significantly reduced expression of the sensitized ambulatory
      motor activity of the cocaine-experienced animals acutely challenged with
      cocaine. Both EMQMCM and MTEP significantly reduced vertical motor activity
      across all cocaine/saline treatment conditions. CONCLUSIONS: These findings
      indicate that the expression of behavioral sensitization to cocaine-induced
      stimulation of locomotor activity may be modulated by group I mGluR antagonists
      (mGluR1 rather than mGluR5), but these effects occur at the dose levels that
      attenuate vertical activity.

PMID- 16896964
TI  - Greater vulnerability to the amnestic effects of ketamine in males.
AB  - RATIONALE: Gender differences both in response to ketamine in animals and general
      cognitive functioning in humans have been observed and suggested to be related to
      modulatory effects of sex hormones on N-methyl-D: -aspartate receptor (NMDA-R)
      functioning. OBJECTIVES: The current study aimed to determine whether there were
      gender differences in response to ketamine in humans. METHODS: Behavioral data
      including positive and negative symptoms (Brief Psychiatric Rating Scale),
      perceptual alterations (Clinician-Administered Dissociative States Scale, CADSS),
      and "high" and "anxiety" states (Visual Analog Scale) from 295 subjects who
      participated in a total of 11 placebo-controlled ketamine studies were analyzed.
      In a subset of subjects, memory (Hopkins Verbal Learning Task: HVLT, n=108) and
      attention (continuous performance task, n=177) data were also analyzed. RESULTS:
      Male participants showed a greater performance decrement on the HVLT after
      ketamine administration compared to women. Men also reported a greater subjective
      sense of memory impairment on a CADSS subscale. No other gender differences in
      behavioral or cognitive measures were observed. CONCLUSIONS: Men showed a greater
      vulnerability to the amnestic effects of ketamine than women. Possible
      explanations of these findings are neuroanatomical and cognitive differences in
      processing of words in men and women and interactions between sex hormones and
      NMDA-R function.

PMID- 16896965
TI  - Preferences among four combination nicotine treatments.
AB  - RATIONALE: Acute nicotine replacement treatments (NRTs) are disliked or misused,
      leading to insufficient nicotine intake and poor outcome. Patches provide steady
      nicotine but are slow and passive. Combining systems may improve efficacy with
      acute NRTs tailored for compliance. OBJECTIVE: To test initial reactions to and
      use preferences among combinations of NRTs. MATERIALS AND METHODS: Smokers (n=27)
      tested four combination NRTs in a 5-day crossover trial: 2/4-mg gum + 15-mg patch
      (G/P), 2/4-mg lozenges + 15-mg patch (L/P), inhaler + 15-mg patch (I/P), and 10
      mg + 15-mg patches (P/P). Subjects rated an NRT combination each day after 5-6 h
      of use and ranked among the NRTs after testing all treatments. RESULTS: Double
      patches (P/P) were ranked highest for "ease of use", "safety", and "use in
      public". However, for "help to quit", 70% preferred some form of acute-patch
      combination (A/P) compared to 30% choosing P/P. For "use under stress" (an
      immediate need), 93% preferred A/P systems compared to 7% choosing P/P. L/P
      ranked lowest for "ease of use", I/P and L/P were lowest on "safety", and I/P
      ranked lowest for "use in public". Expectations of NRTs changed with test
      experience for patches (better) and lozenges (worse). CONCLUSIONS: In brief
      testing, all combinations were acceptable. P/P was favored for ease, safety, and
      public use, but a majority chose A/P systems for help in quitting and use under
      stress. Combined use is viable and needs to be made known and accessible to
      smokers.

PMID- 16896966
TI  - Decreased response rates by the combination of histamine and IL-2 in melphalan
      based isolated limb perfusion.
AB  - Histamine (Hi) combined to melphalan in a rat experimental model of isolated limb
      perfusion (ILP) for lower limb soft tissue sarcoma, resulted in overall response
      rates (OR) of 66%. Likewise, ILP with interleukin-2 (IL-2) resulted in OR of 67%,
      when combined to melphalan, in the same experimental model. In systemic
      immunotherapy, the combination of IL-2 and Hi has been used for solid tumor
      treatment based on immunomodulatory effects. In this study, we used our well
      established ILP experimental model to evaluate whether the synergistic effect
      between the two drugs seen in the systemic setting, could further improve
      response rates in a loco-regional setting. Histological evaluation was done
      directly and 24 h after ILP. Melphalan uptake by tumor and muscle were measured.
      Hi and IL-2 together, combined to melphalan in the ILP led to OR of only 28%.
      Histology of tumors demonstrated partial loss of Hi-induced hemorrhagic effect
      when IL-2 was present. Melphalan accumulation in the tumor when both Hi and IL-2
      were added (3.1-fold) was very similar to accumulation with Hi only (2.8-fold),
      or IL-2 only (3.5-fold) combined to melphalan. In vitro there was no synergy
      between the drugs. In conclusion there was a negative synergistic effect between
      IL-2 and Hi in the regional setting.

PMID- 16896967
TI  - Successful tumor eradication was achieved by collaboration of augmented cytotoxic
      activity and anti-angiogenic effects following therapeutic vaccines containing
      helper-activating analog-loaded dendritic cells and tumor antigen DNA.
AB  - We reported previously that pigeon cytochrome c-derived peptides (Pan-IA), which
      bind broad ranges of MHC class II molecules efficiently, activate T helper (Th)
      function in mice. In an experimental model, Pan-IA DNA vaccines augmented
      antitumor immunity in tumor antigen-immunized mice. To elicit more potent
      antitumor immunity and to eradicate tumors in a therapeutic setting, Pan-IA
      loaded dendritic cells (DCs) were inoculated in combination with vaccines
      including ovalbumin (OVA) antigen DNA in tumor-bearing mice. Seventy percent of
      the immunized mice survived tumor-free for at least 4 months after treatment. In
      contrast, mice vaccinated with OVA DNA, either with or without naive DCs, did not
      eliminate the tumors and died within 5 weeks. Only in mice vaccinated with OVA
      DNA and Pan-IA-loaded DCs were both cytotoxic and helper responses specific for
      OVA induced at the spleen and tumor sites as well as at the vaccination sites.
      Furthermore, accumulation of OVA-specific CD4(+) and CD8(+) T lymphocytes and
      interferon-gamma-mediated anti-angiogenesis were observed in the tumors of these
      mice. Thus, the combined vaccination primed both tumor-specific cytotoxicity and
      helper immunity resulting in augmented tumor lysis ability and anti-angiogenic
      effects. This is the first report to show that most established tumors were
      successfully eradicated by collaboration of potent antitumor immunity and anti
      angiogenic effects by vaccination with tumor antigens and helper-activating
      analogs. This novel vaccination strategy is broadly applicable, regardless of
      identifying helper epitopes in target molecules, and contributes to the
      development of therapeutic cancer vaccines.

PMID- 16896968
TI  - Endowing self-binding feature restores the activities of a loss-of-function
      chimerized anti-GM2 antibody.
AB  - Our previous studies have described a rare type of antibody that spontaneously
      binds to itself, or homodimerizes. This self-binding, or autophilic antibody
      provides stronger protection against bacterial infection than a non-self-binding
      antibody with identical specificity and affinity, due to an increase of polymeric
      avidity. Furthermore, we have shown that a peptide derived from the self-binding
      domain of the autophilic T15 antibody can be crosslinked to the Fc carbohydrate
      of monoclonal antibodies specific for the B-cell receptor of B-cell tumors. These
      peptide-crosslinked antibodies can exert self-binding properties, leading to an
      increase in binding efficiency to the target cells as well as an increase in
      potential to induce apoptosis. Herein, we report a novel finding that
      crosslinking of the autophilic T15 peptide rescues a loss-of-function chimerized
      (ch) anti-GM2 antibody. The parental antibody demonstrates in vivo anti-tumor
      activity against melanoma xenografts. The T15 peptide-conjugated antibody shows
      the ability to bind to itself, as well as an increased binding to its antigen,
      ganglioside GM2. Moreover, the peptide-conjugated antibody also demonstrates an
      increased ability to bind to two GM2-positive tumor cell lines and notably
      important, restores its ability to induce apoptosis in two types of tumor cells.
      These results provide strong support for the clinical potential of the autophilic
      technology.

PMID- 16896969
TI  - [The role of stress in the pathogenesis of tinnitus and in the ability to cope
      with it].
AB  - Besides the impairment of somatic functions, other factors including stress, and
      psychological and social characteristics are known to be important factors in the
      pathogenesis of tinnitus and the ability to cope with it. Existing coping
      strategies and psychosocial factors may have an influence on the degree of stress
      perceived through tinnitus. In the case of missing habituation, serious
      psychological, neurological and immunological responses to tinnitus are possible.
      In order to reduce the cognitive and emotional tinnitus-distress associated with
      this, there should be a focus on providing functional coping strategies combined
      with cognitive behavioural elements.

PMID- 16896961
TI  - Guidelines on nicotine dose selection for in vivo research.
AB  - RATIONALE: This review provides insight for the judicious selection of nicotine
      dose ranges and routes of administration for in vivo studies. The literature is
      replete with reports in which a dosaging regimen chosen for a specific nicotine
      mediated response was suboptimal for the species used. In many cases, such
      discrepancies could be attributed to the complex variables comprising species
      specific in vivo responses to acute or chronic nicotine exposure. OBJECTIVES:
      This review capitalizes on the authors' collective decades of in vivo nicotine
      experimentation to clarify the issues and to identify the variables to be
      considered in choosing a dosaging regimen. Nicotine dose ranges tolerated by
      humans and their animal models provide guidelines for experiments intended to
      extrapolate to human tobacco exposure through cigarette smoking or nicotine
      replacement therapies. Just as important are the nicotine dosaging regimens used
      to provide a mechanistic framework for acquisition of drug-taking behavior,
      dependence, tolerance, or withdrawal in animal models. RESULTS: Seven species are
      addressed: humans, nonhuman primates, rats, mice, Drosophila, Caenorhabditis
      elegans, and zebrafish. After an overview on nicotine metabolism, each section
      focuses on an individual species, addressing issues related to genetic
      background, age, acute vs chronic exposure, route of administration, and
      behavioral responses. CONCLUSIONS: The selected examples of successful dosaging
      ranges are provided, while emphasizing the necessity of empirically determined
      dose-response relationships based on the precise parameters and conditions
      inherent to a specific hypothesis. This review provides a new, experimentally
      based compilation of species-specific dose selection for studies on the in vivo
      effects of nicotine.

PMID- 16896970
TI  - [Transcranial magnetic stimulation for the treatment of tinnitus].

PMID- 16896973
TI  - [Recurring, severe upper abdominal pain in a 45 year old patient].
AB  - A 45-year-old patient presented with a history of recurrent abdominal pain of
      unknown origin. The CT scan of the abdomen demonstrated a thickened mesenteric
      root and a segmental ileus of the jejunum. Laparotomy revealed a neuroendocrine
      tumour of the small bowel. Such tumours are rare causes of recurrent abdominal
      pain. Especially when the CT scan of the abdomen reveals mesenteric abnormalities
      (desmoplastic reaction) and/or a segmental ileus, a neuroendocrine tumour of the
      small bowel should be considered. The therapy of choice is resection of the
      tumour followed by systemic therapy including somatostain analogues and
      chemotherapy in the case of a hormone secreting tumour or metastases.

PMID- 16896971
TI  - [New therapy possibilities for arrhythmias using catheter ablation].
AB  - Radiofrequency current ablation has been developed over the last 20 years to be
      the standard approach for treating tachycardia by catheter ablation. By combining
      new 3-D imaging technology (CT and MRI) with 3-D electrophysiologic mapping
      systems, a new tool has been created to display the cardiac activation sequence
      of the individual. These technologies are extremely important for the treatment
      of complex arrhythmias such as the catheter ablation of atrial fibrillation.
      Instead of the conventional "point by point" linear ablation procedure, balloon
      catheters have been applied to a circumferential linear lesion in a "single shot"
      procedure using, for example, cryothermia, ultrasound or laser energy. Finally,
      magnetic navigation is a new steering tool for performing ablation procedures,
      leading to reduced exposure to ionizing radiation.

PMID- 16896974
TI  - Did ice-age bovids spread tuberculosis?
AB  - Pathognomonic metacarpal undermining is a skeletal pathology that has been
      associated with Mycobacterium tuberculosis in bovids. Postcranial artiodactyl,
      perissodactyl, and carnivore skeletons were examined in major university and
      museum collections of North America and Europe for evidence of this and other
      pathology potentially attributable to tuberculosis. Among nonproboscidean mammals
      from pre-Holocene North America, bone lesions indicative of tuberculosis were
      restricted to immigrant bovids from Eurasia. No bone lesions compatible with
      diagnosis of tuberculosis were found in large samples of other pre-Holocene (164
      Oligocene, 397 Miocene, and 1,041 Plio-Pleistocene) North American mammals,
      including 114 antilocaprids. Given the unchanged frequency of bovid tubercular
      disease during the Pleistocene, it appears that most did not die from the disease
      but actually reached an accommodation with it (as did the mastodon) (Rothschild
      and Laub 2006). Thus, they were sufficiently long-lived to assure greater spread
      of the disease. The relationships of the proboscidean examples need further
      study, but present evidence suggests a Holarctic spread of tuberculosis during
      the Pleistocene, with bovids acting as vectors. While the role of other animals
      in the transmission of tuberculosis could be considered, the unique accommodation
      achieved by bovids and mastodons makes them the likely "culprits" in its spread.

PMID- 16896975
TI  - "Winter" aggregations, colony cycle, and seasonal phenotypic change in the paper
      wasp Polistes versicolor in subtropical Brazil.
AB  - Social wasps from temperate zones have clear annual colony cycles, and the young
      queens hibernate during winter. In the subtropics, the only previously reported
      evidence for the existence of "hibernation" is the facultative winter
      aggregations of females during harsh climate conditions. As in temperate-zone
      species analyzed so far, we show in this study that in the paper wasp, Polistes
      versicolor, a subtropical species, body size increases as an unfavorable season
      approaches. Our morphological studies indicate that larger females come from
      winter aggregations--that is, they are new queens. Multivariate analyses indicate
      that size is the only variable analyzed that shows a relationship to the
      differences. Given the absence of a harsh climate, we suggest that the occurrence
      of winter aggregations in tropical P. versicolor functions to allow some females
      to wait for better environmental conditions to start a new nest, rather than all
      being obliged to start a new nest as soon as they emerge.

PMID- 16896976
TI  - The effects of different predator species on antipredator behavior in the
      Trinidadian guppy, Poecilia reticulata.
AB  - Different types of predators often elicit different antipredator responses in a
      common type of prey. Alternatively, some prey species may adopt a general
      response, which provides limited protection from many different types of
      predator. The Trinidadian guppy, Poecilia reticulata, is faced with a wide range
      of different predators throughout its range and is known to display varying
      levels of antipredator behavior depending on the predator assemblage. Pike
      cichlids, Crenicichla frenata, are regarded as the primary aquatic guppy predator
      in streams in the northern mountain range in Trinidad. As such, they are seen to
      be responsible for many of the differences in morphology, life history traits,
      and behavior between guppy populations from areas with few predators and those
      from areas with many pike cichlids. In this study we investigated how guppies
      responded when faced with different predator species using three common aquatic
      predators. We exposed shoals of ten guppies to one out of four treatments: no
      predator (control), pike cichlid, acara cichlid (Aequidens pulcher), and wolf
      fish (Hoplias malabaricus); and we made behavioral observations on both focal
      individuals and the shoal as a whole. Guppies showed significantly greater levels
      of predator inspection and shoaling behavior, foraged less, spent more time in
      the surface water, and stayed in significantly larger shoals when faced with pike
      cichlids than in other treatments. We discuss these results in the context of
      multiple predator effects.

PMID- 16896977
TI  - The amplitude of force variability is correlated in the knee extensor and elbow
      flexor muscles.
AB  - The purpose of this study was to determine motor output variability for different
      muscles in the same individuals. Ten young (21.7 +/- 3.4 years) and ten elderly
      (72.1 +/- 3.9 years) men underwent assessment of maximal isometric (MVC) and
      dynamic (1-RM) strength, and performed constant-force (2-50% MVC), constant-load
      (5-50% 1-RM load), and unloaded postural contractions as steadily as possible
      with the first dorsal interosseus (FDI), elbow flexors (EF), and knee extensors
      (KE). The coefficient of variation (CV) of force for isometric contractions and
      the standard deviation (SD) of acceleration for concentric, eccentric, and
      postural contractions were calculated. The 1-RM load, the CV of force for four of
      five isometric target forces, and the SD of acceleration during postural
      contractions were correlated between the EF and KE muscles. MVC force, 1-RM load,
      and SD of acceleration during postural contractions were not correlated between
      the FDI/EF or FDI/KE. The CV of force was correlated between the FDI/EF and
      FDI/KE for two of five isometric target forces. The SD of acceleration during
      concentric and eccentric contractions was not correlated between muscles. The
      normalized fluctuations during isometric contractions were greater for the FDI
      compared with the EF and KE. Elderly adults displayed greater fluctuations only
      for the FDI during low-force isometric and postural contractions. The dominant
      frequency of fluctuations was similar for the EF and KE muscles. The correlated
      fluctuations for the EF and KE muscles, within subjects, suggests that the two
      motor neuron pools transform the various neural inputs similarly.

PMID- 16896978
TI  - Microstimulation of V1 delays visually guided saccades: a parametric evaluation
      of delay fields.
AB  - Electrical microstimulation of macaque striate cortex (area V1) delays the
      execution of saccadic eye movements made to a visual target placed in the
      receptive field of the stimulated neurons. The region of visual space within
      which saccades are delayed is called a delay field. We examined the effects of
      changing the parameters of stimulation and target size on the size of a delay
      field. Rhesus monkeys were required to generate a saccadic eye movement to a
      punctate and white visual target presented within or outside the receptive field
      of the neurons under study. On 50% of trials, a train of stimulation consisting
      of 0.2-ms anode-first pulses was delivered to the neurons before the onset of the
      visual target. Stimulations were performed in the operculum at 0.9-2.0 mm below
      the cortical surface. It was found that increases in current (50-100 microA),
      pulse frequency (100-300 Hz), or train duration (75-300 ms) increased the size of
      a delay field and increases in target size (0.1 degrees -0.2 degrees of visual
      angle) decreased the size of a delay field. Delay fields varied in size between
      0.1 and 0.6 degrees of visual angle. These results are related to the properties
      of phosphenes induced by electrical stimulation of V1 in humans and compared to
      the interference effects observed following transcranial magnetic stimulation of
      human V1.

PMID- 16896979
TI  - Eye movements coordinated with steering benefit performance even when vision is
      denied.
AB  - When driving along a winding road, eye movements and steering are tightly linked.
      When approaching a bend, the driver looks across to the inside kerb (the tangent
      point) some time before turning the steering wheel. All drivers we have tested
      show this optimal coordination, without which driving is impaired. An intriguing
      question is how much of the benefit for steering arises just from moving the eyes
      in this coordinated way (ahead of steering and in the same direction), and how
      much from the visual information that the eyes move to acquire, in this instance
      the foveated tangent point. This can be answered by dissociating the two, by
      reducing visibility of the road ahead (and crucially of the tangent point) to a
      level at which drivers might or might not choose to move their eyes but, if they
      do, will not gain the information they seek. Twenty subjects repeatedly drove a
      simulated stage of the World Rally Championship. With full visibility, they
      exhibited the usual coordination of eye movements and steering. Subsequently,
      visibility was reduced on the left hand side. Drivers who persisted in making eye
      movements coordinated with steering to the left, despite the fact that they could
      no longer see the tangent point on that side, performed better than drivers who
      under the identical conditions did not look to the left. This confirms that the
      making of coordinated eye movements itself benefits steering, even when the eye
      movements do not yield the visual information sought.

PMID- 16896980
TI  - The effect of early musical training on adult motor performance: evidence for a
      sensitive period in motor learning.
AB  - Developmental changes in the human brain coincide with and underlie changes in a
      wide range of motor and cognitive abilities. Neuroimaging studies have shown that
      musical training can result in structural and functional plasticity in the brains
      of musicians, and that this plasticity is greater for those who begin training
      early in life. However, previous studies have not controlled for differences
      between early-trained (ET) and late-trained (LT) musicians in the total number of
      years of musical training and experience. In the present experiment, we tested
      musicians who began training before and after the age of 7 on learning of a timed
      motor sequence task. The groups were matched for years of musical experience,
      years of formal training and hours of current practice. Results showed that ET
      musicians performed better than LT musicians, and that this performance advantage
      persisted after 5 days of practice. Performance differences were greatest for a
      measure of response synchronization, suggesting that early training has its
      greatest effect on neural systems involved in sensorimotor integration and
      timing. These findings support the idea that there may be a sensitive period in
      childhood where enriched motor training through musical practice results in long
      lasting benefits for performance later in life. These results are also consistent
      with the results of studies showing structural changes in motor-related regions
      of the brain in musicians that are specifically related to training early in
      life.

PMID- 16896981
TI  - The effect of target modality on visual and proprioceptive contributions to the
      control of movement distance.
AB  - Abstract The goal of this study was to determine whether the sensory nature of a
      target influences the roles of vision and proprioception in the planning of
      movement distance. Two groups of subjects made rapid, elbow extension movements,
      either toward a visual target or toward the index fingertip of the unseen
      opposite hand. Visual feedback of the reaching index fingertip was only available
      before movement onset. Using a virtual reality display, we randomly introduced a
      discrepancy between actual and virtual (cursor) fingertip location. When subjects
      reached toward the visual target, movement distance varied with changes in visual
      information about initial hand position. For the proprioceptive target, movement
      distance varied mostly with changes in proprioceptive information about initial
      position. The effect of target modality was already present at the time of peak
      acceleration, indicating that this effect include feedforward processes. Our
      results suggest that the relative contributions of vision and proprioception to
      motor planning can change, depending on the modality in which task relevant
      information is represented.

PMID- 16896982
TI  - Patterns of primary afferent depolarization of segmental and ascending
      intraspinal collaterals of single joint afferents in the cat.
AB  - We have examined in the anesthetized cat the threshold changes produced by
      sensory and supraspinal stimuli on intraspinal collaterals of single afferents
      from the posterior articular nerve (PAN). Forty-eight fibers were tested in the
      L3 segment, in or close to Clarke's column, and 70 fibers in the L6-L7 segments
      within the intermediate zone. Of these, 15 pairs of L3 and L6-L7 collaterals were
      from the same afferent. Antidromically activated fibers had conduction velocities
      between 23 and 74 m/s and peripheral thresholds between 1.1 and 4.7 times the
      threshold of the most excitable fibers (xT), most of them below 3 xT. PAN
      afferents were strongly depolarized by stimulation of muscle afferents and by
      cutaneous afferents, as well as by stimulation of the bulbar reticular formation
      and the midline raphe nuclei. Stimulation of muscle nerves (posterior biceps and
      semitendinosus, quadriceps) produced a larger PAD (primary afferent
      depolarization) in the L6-L7 than in the L3 terminations. Group II were more
      effective than group I muscle afferents. As with group I muscle afferents, the
      PAD elicited in PAN afferents by stimulation of muscle nerves could be inhibited
      by conditioning stimulation of cutaneous afferents. Stimulation of the cutaneous
      sural and superficial peroneal nerves increased the threshold of few terminations
      (i.e., produced primary afferent hyperpolarization, PAH) and reduced the
      threshold of many others, particularly of those tested in the L6-L7 segments.
      Yet, there was a substantial number of terminals where these conditioning stimuli
      had minor or no effects. Autogenetic stimulation of the PAN with trains of pulses
      increased the intraspinal threshold in 46% and reduced the threshold in 26% of
      fibers tested in the L6-L7 segments (no tests were made with trains of pulses on
      fibers ending in L3). These observations indicate that PAN afferents have a
      rather small autogenetic PAD, particularly if this is compared with the effects
      of heterogenetic stimulation. Therefore, the depression of the PAN intraspinal
      fields produced by autogenetic stimulation described by Rudomin et al. (Exp Brain
      Res DOI 10.1007/s00221-006-0600-x, 2006) may be ascribed to other mechanisms
      besides a GABAa PAD. It is suggested that the small or no autogenetic PAD
      displayed by the examined joint afferents prevents presynaptic filtering of their
      synaptic actions and preserves the original information generated in the
      periphery. This could be important for proper adjustment of limb position.

PMID- 16896983
TI  - Tonic and phasic differential GABAergic inhibition of synaptic actions of joint
      afferents in the cat.
AB  - The aim of this study was to examine the functional organization of the spinal
      neuronal networks activated by myelinated afferent fibers in the posterior
      articular nerve (PAN) of the anesthetized cat. Particular attention was given to
      the tonic and phasic GABAa inhibitory modulation of these networks. Changes in
      the synaptic effectiveness of the joint afferents were inferred from changes in
      the intraspinal focal potentials produced by electrical stimulation of the PAN.
      We found that conditioning stimulation of cutaneous nerves (sural, superficial
      peroneus and saphenous) and of the nucleus raphe magnus often inhibited, in a
      differential manner, the early and late components of the intraspinal focal
      potentials produced by stimulation of low and high threshold myelinated PAN
      afferents, respectively. The degree of the inhibition depended on the strength of
      both the conditioning and test stimuli and on the segmental level of recording.
      Conditioning stimulation of group I muscle afferents was less effective, but
      marked depression of the early and late focal potentials was produced by stimuli
      exceeding 5 xT. The i.v. injection of 1-2.5 mg/kg of picrotoxin, a GABAa blocker,
      had relatively minor effects on the early components of the PAN focal potentials,
      but was able to induce a significant increase of the late components. It also
      reduced the inhibitory effects of cutaneous and joint nerve conditioning on PAN
      focal responses. Conditioning autogenetic stimulation with high-frequency trains
      depressed the PAN focal potentials. The late components of the PAN responses
      remained depressed several minutes after discontinuing the conditioning train,
      even after picrotoxin administration. The present observations indicate that the
      neuronal networks activated by the low threshold PAN afferents show a relatively
      small post-activation depression and appear to be subjected to a minor tonic
      inhibitory GABAa control. In contrast, the pathways activated by stimulation of
      high threshold myelinated afferents have a strong post-activation depression and
      are subjected to a significant tonic GABAergic modulation. These contrasting
      features, together with the phasic differential GABAergic inhibition of the
      responses produced by stimulation of the different populations of joint
      afferents, may contribute to the preservation of the original information on
      joint position transmitted by large diameter joint afferents, in contrast with
      the tonic presynaptic inhibition exerted on the fine myelinated joint afferents,
      which may be involved in the adjustment of compensatory reactions to
      inflammation.

PMID- 16896984
TI  - Cerebral cortical processing of swallowing in older adults.
AB  - While brain-imaging studies in young adults have implicated multiple cortical
      regions in swallowing, investigations in older subjects are lacking. This study
      examined the neural representations of voluntary saliva swallowing and water
      swallowing in older adults. Nine healthy females were examined with event-related
      functional magnetic resonance imaging (fMRI) while laryngeal swallow-related
      movements were recorded. Swallowing in the older adults, like young adults,
      activated multiple cortical regions, most prominently the lateral pericentral,
      perisylvian, and anterior cingulate cortex. Activation of the postcentral gyrus
      was lateralized to the left hemisphere for saliva and water swallowing,
      consistent with our findings in young female subjects. Comparison of saliva and
      water swallowing revealed a fourfold increase in the brain volume activated by
      the water swallow compared to the saliva swallow, particularly within the right
      premotor and prefrontal cortex. This task-specific activation pattern may
      represent a compensatory response to the demands of the water swallow in the face
      of age-related diminution of oral sensorimotor function.

PMID- 16896986
TI  - Topiramate and cortical excitability in humans: a study with repetitive
      transcranial magnetic stimulation.
AB  - Repetitive transcranial magnetic stimulation (rTMS) delivered at 5 Hz frequency
      and suprathreshold intensity progressively increases the size of muscle evoked
      potentials (MEPs) and the duration of the cortical silent period (CSP) in normal
      subjects. The aim of this study was to evaluate the effects of topiramate (TPM)
      at different doses on cortical excitability variables tested with rTMS. We tested
      the facilitation of the MEP size and CSP duration evoked by focal rTMS in eight
      patients before and after treatment with TPM at different doses for chronic
      neuropathic pain. In each patient, rTMS (5 Hz frequency-120% resting motor
      threshold) was applied at baseline and during the TPM induction phase (drug
      intake schedule: week I 25 mg/day, week II 50 mg/day, week III 75 mg/day, week IV
      100 mg/day) and total TPM plasma concentrations were measured. The effects on the
      MEP size of 5 Hz-rTMS delivered over repeated sessions were tested in eight
      control subjects. TPM had no effect on the resting motor threshold. Antiepileptic
      treatment at increasing doses abolished the normal rTMS-induced MEP facilitation.
      ANOVA showed that this was a dose-related effect. Accordingly, in patients
      receiving TPM at higher doses (75 and 100 mg) rTMS failed to elicit the MEP
      facilitation. TPM left the progressive lengthening of the CSP during the rTMS
      train unchanged. In control subjects, rTMS applied over repeated sessions
      elicited a constant increase in MEP size. Our results suggest that TPM modulates
      the excitatory intracortical interneurons probably by altering rTMS-induced
      synaptic potentiation. These drug-induced effects are related to TPM doses and
      plasma concentrations. In conclusion, rTMS may be useful for quantifying the
      effectiveness of antiepileptic drugs and for assessing individual responses to
      different drugs but acting through similar mechanisms, thus combining functional
      neurophysiological information and laboratory data.

PMID- 16896985
TI  - Asymmetry of interhemispheric interaction in left-handed subjects.
AB  - In right-handed subjects the execution of a simple finger-tapping task is
      associated with an asymmetry of interhemispheric interaction, probably suggesting
      that the dominant left hemisphere inhibits the right one. The present study
      investigated the left-handed subjects in order to elucidate whether this
      asymmetry is related to handedness. Nineteen healthy subjects performed unimanual
      left, right, and bimanual auditorily paced finger-tapping tasks while
      neuromagnetic activity was recorded with a 122-channel whole-head
      neuromagnetometer (MEG). Simultaneously, we recorded activity of the first dorsal
      interosseus (FDI) muscle of both hands. By using the analysis tool dynamic
      imaging of coherent sources (DICS), oscillatory activity at alpha as well as at
      beta frequency within the primary sensorimotor (S1/M1) and premotor (PMC) cortex
      was localized. As expected, we observed oscillatory coupling between S1/M1 and
      PMC contralateral to the moving hand. Furthermore, coupling between left PMC and
      bilateral S1/M1 occurred in each movement condition, suggesting that the left PMC
      modulates neural activity in bilateral primary sensorimotor cortices independent
      of the moving hand. Coupling between bilateral S1/M1 occurred more frequently and
      significantly stronger during the right hand condition. This result demonstrates
      the same interhemispheric coupling pattern as in right-handed subjects,
      suggesting that the asymmetry of this interaction is not due to hand dominance. A
      specialization of the left premotor cortex either for superior motor control per
      se or for the execution of sequential tasks might account for these results.

PMID- 16896987
TI  - Antipolymer antibody is not associated with fibromyalgia in Korean female
      patients.
AB  - To examine the levels of antipolymer antibody (APA) in Korean female patients
      with fibromyalgia (FM) and to determine whether the levels of APA correlate with
      FM severity. Serum samples from patients with FM (n = 69), patients with
      rheumatoid arthritis (RA) (n = 71), and controls (n = 75) were assayed for APA.
      All of the subjects were female, and the controls were age-matched healthy
      volunteers. FM tender point counts and scores were examined, and FM patients were
      asked to complete a Korean version of the Fibromyalgia Impact Questionnaire
      (FIQ), the State-Trait Anxiety Inventory (STAI), and the Beck Depression
      Inventory (BDI). APA-positive samples were detected in five (7.2%) of the 69 FM
      patients, seven (9.9%) of the 71 RA patients, and four (5.3%) of the 75 controls.
      The prevalence of seropositivity and the level of APA in FM patients did not
      differ from those in RA patients and controls. The proportion positive for APA
      was not higher for FM patients with severe symptoms than for FM patients with
      mild symptoms. There was a negative association between the APA level and age.
      The APA level in FM patients was not correlated with age at diagnosis, age at
      symptom onset, disease duration, education, tender point counts and scores, FIQ,
      STAI, or BDI. The prevalence of APA in Korean FM patients was quite low. Owing to
      the low prevalence of APA in this study, the APA assay did not distinguish FM
      patients with severe symptoms from those with mild symptoms.

PMID- 16896988
TI  - Legends of thoracic outlet syndrome.

PMID- 16896989
TI  - Acute ulnar neuropathy at the wrist: a case report and review of the literature.
AB  - Acute ulnar neuropathy at the wrist is an extremely uncommon condition, at times
      requiring a high index of suspicion for the diagnosis. Clinical presentations of
      ulnar nerve lesions at the wrist and hand show variations due to the complex
      anatomic course of the nerve in distal sites. We report a case of acute ulnar
      neuropathy at the wrist caused by a ganglion in Guyon's canal, being initially
      misinterpreted as flexor tenosynovitis. The accurate diagnosis of selective
      distal motor neuropathy of ulnar nerve was made electrophysiologically. Magnetic
      resonance imaging revealed a well defined soft tissue mass consistent with a
      ganglion, compressing the ulnar nerve in Guyon's canal. Entrapment neuropathies
      are one of the common conditions handled by physiatrists. Ulnar nerve lesions at
      the wrist should be kept in mind in the differential diagnosis of patients with
      wrist or hand pain. Magnetic resonance imaging is a useful method in the
      anatomical evaluation of acute focal neuropathies.

PMID- 16896990
TI  - Serious infections under treatment with TNF-alpha antagonists compared to
      traditional DMARDs in patients with rheumatoid arthritis.
AB  - Biological treatments aiming to neutralize TNF-alpha (tumour necrosis factor
      alpha) (infliximab, adalimumab and etanercept) are increasingly used to treat
      rheumatoid arthritis (RA). Although increased frequency has not been observed in
      randomized clinical trials with TNF-alpha antagonist agents, postmarketing
      surveillance suggests that infections might be serious consequences of these
      therapies. Our aim was to compare infections in patients with RA under treatment
      with disease-modifying antirheumatic drugs (DMARDs) and TNF-alpha antagonists in
      a university outpatient rheumatology clinic in Turkey. A total of 130 RA patients
      treated with DMARDs and 48 treated with TNF-alpha antagonists were analysed for
      the incidence of infections. Patients taking TNF-alpha antagonists were also
      reviewed for infections before these therapies. The incidence of serious
      infections was 7/100 patient-years before TNF-alpha antagonists and 8.6/100
      patient-years in DMARDs group. The incidence rose to 17/100 patient-years during
      therapy with TNF-alpha antagonists. In patients with RA on routine follow-up,
      treatment with TNF-alpha antagonists seems to carry an increased risk of
      infections compared to traditional DMARDs.

PMID- 16896991
TI  - Long-term survival after resection of extrahepatic recurrence of hepatocellular
      carcinoma at the right colon.

PMID- 16896992
TI  - Clinicopathologic and prognostic significance of matrix metalloproteinases in
      rectal cancer.
AB  - BACKGROUND AND AIMS: The aim of this study was to determine the prognostic role
      of matrix metalloproteinases in rectal cancer. MATERIALS AND METHODS: Formalin
      fixed and paraffin-embedded tissue sections of 94 rectal carcinomas were used for
      the immunohistochemical analysis of matrix metalloproteinases (MMP)-2, MMP-7, MT1
      MMP, and tissue inhibitor of metalloproteinases (TIMP)-2. Inclusion criteria were
      sporadic rectal adenocarcinoma resected curatively (including total mesorectal
      excision), adjuvant radiochemotherapy in UICC stages II and III, and complete
      intra-institutional follow-up. Results of immunohistochemistry were correlated
      with clinical and histopathologic data from the prospective rectal cancer
      registry and prognosis. End points of the prognostic analysis were tumor
      progression caused by local and/or distant recurrence and 5-year survival
      (disease-free and overall). To assess prognostic significance, statistics
      included univariate and multivariate analysis (p<0.05 statistically significant).
      RESULTS: Of the 94 rectal carcinomas, 35% (33/94) showed an epithelial MMP-2
      expression, 77% (72/94) were MMP-2 positive in the stroma. Fifty-four percent
      (51/94) were MMP-7 positive, and 47% (46/94) were positive for both MT1-MMP and
      TIMP-2. The stromal MMP-2 staining pattern was correlated with the depth of
      invasion (pT status, p=0.006) with MMP-7 (p=0.016) and TIMP-2 expression
      (p=0.036). Positive expression of MMP-2 in tumor epithelium was correlated with
      MMP-7 (p=0.027), MT1-MMP (p=0.036), and TIMP-2 expression (p<0.0001). A positive
      staining pattern of MMP-7 was significantly correlated with depth of invasion and
      TIMP-2 (p<0.01). The positive staining pattern of MT1-MMP was correlated with
      epithelial MMP-2 (p=0.036), MMP-7 (p=0.004), and TIMP-2 expression (p=0.002).
      TIMP-2 immunoreactivity correlated with depth of invasion (p=0.013), epithelial
      MMP-2 (p<0.001), stromal MMP-2 (p=0.036), MMP-7 (p<0.001), and MT1-MMP (p=0.002).
      Neither pattern correlated with age, gender, tumor stage (UICC), grading,
      preoperative serum carcinoembryonic antigen (CEA) level, or nodal status
      (p>0.05). Within a mean follow-up of 46 months, tumor progression, caused by
      either local recurrence or distant metastasis, occurred in 14 patients (15.4%).
      There was no significant association between the MMP expression and the incidence
      of local and/or distant recurrence. In terms of survival, preoperative CEA level
      (disease-free 5-year survival 46% with increased CEA vs 70% with normal CEA,
      p=0.01; overall 5-year survival 43 vs 74%, p<0.01) and UICC stage were the only
      factors to be significantly related to 5-year survival by univariate analysis,
      whereas the metalloproteinases failed to show a significant association. In
      multivariate analysis, CEA and UICC stage were not identified as independent
      factors predictive of survival. CONCLUSION: MMP-2, MMP-7, MT1-MMP, and TIMP-2 do
      not appear to be significant predictors of prognosis in a homogenous collective
      of curatively resected rectal adenocarcinomas.

PMID- 16896993
TI  - Clinical and manometric results of endorectal advancement flaps for complex anal
      fistula.
AB  - BACKGROUNDS AND AIM: Endorectal advancement flap repair is a well-recognized
      method for the treatment of complex anorectal fistula. The purpose of this study
      was to prospectively assess the clinical and functional results of endorectal
      advancement flaps for complex anorectal fistula and to identify factors that
      affect outcome. MATERIALS AND METHODS: A prospective study of 56 patients was
      performed. Clinical and functional results were studied using the Wexner
      continence scale and anal manometry before and after surgery. Factors associated
      with recurrence and incontinence were analyzed by univariate and multivariate
      regression analysis. RESULTS: Sixty endorectal flaps were constructed in 56
      patients. Mean age was 49 years (range 24-74). The fistula was of cryptoglandular
      origin in 91.1% cases. Mean follow-up was 43.8 months. The technique was repeated
      in four patients because of recurrence (7.1%), with subsequent healing in all
      cases. There were significant reductions in maximum resting pressure 3 months
      after surgery (83.6+/-33.2 vs 45.6+/-18.3, p<0.001) and maximum squeeze pressure
      (208.8+/-91.5 vs 169.5+/-75, p<0.001). Before surgery, five patients (8.9%)
      reported incontinence symptoms. After surgery, 78.6% patients had normal
      continence, seven patients (12.5%) complained of minor incontinence, and five
      (9%) had major continence disturbances. None of the variables studied (age, sex,
      previous fistula surgery, rectovaginal fistula, and Crohn's disease) affected the
      outcome of the procedure in multivariate analysis. CONCLUSIONS: Endorectal
      advancement flap repair is an effective technique for complex anal fistula, with
      a low recurrence rate (7.1%). Patients (21.4%) reported disturbed anal
      continence. It is still not possible to identify factors that are predictive of
      failure or incontinence.

PMID- 16896995
TI  - Pseudomembranous colitis presenting as an isolated colonic stricture.

PMID- 16896994
TI  - N-Acetyltransferase (NAT) 2 acetylator status and age of tumour onset in patients
      with sporadic and familial, microsatellite stable (MSS) colorectal cancer.
AB  - INTRODUCTION: N-Acetyltransferase (NAT) 2 is an important enzyme involved in the
      metabolism of different xenobiotics, including potential carcinogens. Allelic
      variants of the NAT2 gene are determined by a pattern of single nucleotide
      polymorphisms (SNPs) resulting in slow (SA), intermediate (IA) or rapid
      acetylator (RA) phenotypes and causing the individual differences in the NAT2
      metabolic capacity. To clarify the potential modifying role of the NAT2
      acetylator status in microsatellite stable (MSS) colorectal cancer (CRC), we
      studied 140 patients with sporadic CRC (group 1) and 69 patients with CRC who met
      at least one criterion of the revised Bethesda guidelines (group 2).
      OBSERVATIONS: We did not observe any significant difference in the NAT2
      acetylator status frequency between patients in both groups and 100 healthy
      controls (P=0.486). Regardless of a younger median age of tumour onset (AO) of 41
      years in group 2 patients compared to 64 years in group 1 patients, no
      significant difference in AO was found between RA and SA status patients in both
      groups. The median AO in group 1 was 65 years in patients with RA and 63 years
      with SA status (P=0.065). The median AO in group 2 was 40 years in patients with
      RA and 42 years with SA status (P=0.814). Multivariate Cox regression analysis
      revealed that neither the NAT2 acetylator status (P=0.064 and 0.810,
      respectively) nor the gender (P=0.165 and 0.918, respectively) was a risk factor
      for the AO in both groups. These data do not support the hypothesis that the NAT2
      acetylatorship acts as a modifying factor on the AO in sporadic and familial,
      microsatellite stable CRC.

PMID- 16896996
TI  - Malignant fibrous histiocytoma of the sigmoid: a case report and review of the
      literature.
AB  - BACKGROUND: Malignant fibrous histiocytoma (MFH) in the large bowel, which is
      composed of spindle-shaped cells arranged in a pleiomorphic and storiform
      pattern, is an extremely rare tumor. METHODS: We in this study report on a case
      of a 73-year-old man with a sarcoma arising from a diverticular sigmoid without
      any signs of involvement of regional lymph nodes or metastasis to liver or the
      abdomen. RESULTS: A sigmoid resection was performed with an uneventful
      postoperative course. Microscopically, the tumor consisted of bundles of spindle
      shaped and pleiomorphic multinucleated cells without differentiation
      characteristics for other tumors than MFH. SUMMARY: Since the late 1970s, only 22
      case reports of colorectal MFH have been documented, and little is known about
      its histogenesis and optimal treatment. A review of the cases and the world
      literature on immunohistochemistry and treatment is given.

PMID- 16896998
TI  - Kawasaki disease and hyponatremia.

PMID- 16897000
TI  - Changes in renal sodium transport during a systemic inflammatory response.

PMID- 16897001
TI  - Tacrolimus for the treatment of focal segmental glomerulosclerosis resistant to
      cyclosporine A.

PMID- 16896999
TI  - Different pathomechanisms of essential and obesity-associated hypertension in
      adolescents.
AB  - Obesity-induced hypertension and essential hypertension in lean patients are two
      different forms of hypertension. The main goal of this study was to test whether
      there are differences in biochemical parameters between subjects with obesity
      associated hypertension and those with essential hypertension. We examined
      whether the biochemical responses to angiotensin-converting enzyme inhibitor
      (ACEI) ramipril therapy reveal properties of these two conditions that might
      explain the differences in clinical outcome. Before ramipril therapy, the
      hypertensive group exhibited increases in ACE activity (p<0.05), plasma
      malondialdehyde (MDA) concentration and the malondialdehyde/nitric oxide end
      product ratio (MDA/NO(x)) (p<0.05), and decreases in xanthine oxidase (XO)
      activity (p<0.05) and plasma nitric oxide end-product (NO(x)) level (p<0.01).
      Before medication, plasma endothelin-1 (ET-1), plasma leptin, and leptin receptor
      levels were normal. Following ramipril treatment, ACE activity normalized. Before
      ACE inhibitor treatment, the obese-hypertensive group exhibited elevated levels
      of plasma ET-1 (p<0.05), plasma leptin (p<0.01), XO activity (p<0.05), plasma MDA
      and MDA/NO(x) (p<0.05), and reduced levels of plasma NO(x)(p<0.01) and leptin
      receptors (p<0.001). Following medication, the plasma NO(x) level, MDA/NO(x), and
      XO activity returned to normal while ACE activity decreased (p<0.001). In
      patients with essential hypertension, NO availability and ACE activity, and in
      those with obesity-associated hypertension, hyperleptinemic effects, NO level,
      endothelin-1 concentration and XO activity, may be important factors in the
      pathology.

PMID- 16897003
TI  - Acute renal failure due to phenazopyridine (Pyridium) overdose: case report and
      review of the literature.
AB  - Phenazopyridine (Pyridium) is a commonly used urinary tract analgesic. It has
      been associated with yellow skin discoloration, hemolytic anemia,
      methemoglobinemia, and acute renal failure, especially in patients with
      preexisting kidney disease. We report a 17-year-old female with vertically
      transmitted human immunodeficiency virus (HIV) infection, presenting with acute
      renal failure and methemoglobinemia following a suicidal attempt with a single
      1,200 mg ingestion of Pyridium. She had no prior evidence of HIV nephropathy. The
      patient had a progressive nonoliguric renal failure on the 3rd day following the
      ingestion. She was treated with N-acetylcysteine, intravenous carnitine, and
      alkalinization of the urine. Her kidney biopsy revealed acute tubular necrosis
      with no glomerular changes. After 7 days of conservative management, she was
      discharged home with normal kidney function. To our knowledge, this is the second
      smallest amount of Pyridium overdose resulting in acute renal failure with no
      previous history of kidney disease.

PMID- 16897004
TI  - Hyperphosphatemia is prevalent among children with nephrotic syndrome and normal
      renal function.
AB  - The aim of the study was to analyze systematically our observation that children
      with severe nephrotic syndrome (NS) have hyperphosphatemia despite normal kidney
      function. Forty-seven children with NS and normal glomerular filtration rate
      (GFR) were studied [26 with steroid-sensitive nephrotic syndrome (SSNS) and 21
      with persistent NS]. The plasma phosphate level was expressed as the number of
      standard deviations (SDs) from the mean levels in age- and gender-matched
      controls. In SSNS plasma phosphate concentration was elevated (+3.7+/-2.0 SDs)
      during relapse and normalized (-0.7+/-1.7 SDs) in remission. In persistent NS the
      phosphate level was +4.0+/-2.1 SDs. Patients with marked hyperphosphatemia (>4
      SDs) were younger (p<0.001), had lower plasma albumin (p<0.001), and had higher
      urinary protein levels (p<0.05). Hyperphosphatemia did not correlate with GFR,
      plasma calcium, or urinary sodium levels. Children with persistent NS had
      decreased serum 25(OH)D(3) and insulin-like growth factor 1 (IGF-1)
      concentrations. Hyperphosphatemia is prevalent among children with persistent
      nephrotic syndrome and normal renal function, correlates with its severity, and
      may result from increased urinary IGF-1 wasting.

PMID- 16897002
TI  - AT1 antagonist modulates activin-like kinase 5 and TGF-beta receptor II in the
      developing kidney.
AB  - Previous studies by our group have demonstrated that angiotensin-converting
      enzyme (ACE) inhibition in the developing kidney modulates transforming growth
      factor-beta receptors. Blocking of angiotensin II (ANG II) mainly through
      angiotensin II type 1 receptor (AT1) has been implicated in mediating this ACE
      inhibition. The present study was designed to investigate the effects of an AT1
      antagonist, losartan, on transforming growth factor-beta1 (TGF-beta1), TGF-beta
      receptor I [TbetaRI, activin-like kinase (ALK)-1, ALK-5], TGF-beta receptor II
      (TbetaRII), and alpha-smooth muscle actin (alpha-SMA) expression in the
      developing kidney. Newborn rat pups were treated with losartan (30 mg/kg per day)
      or normal saline for 7 days. Kidneys were removed for immunohistochemistry,
      reverse transcription polymerase chain reaction (PCR), and Western blotting of
      TGF-beta1, ALK-1, ALK-5, TbetaRII, and alpha-SMA. Renal ALK-5 and TbetaRII
      protein expressions in the losartan-treated group were found to be significantly
      increased (P<0.05), whereas TGF-beta1, ALK-1, and alpha-SMA protein expressions
      were not changed by losartan treatment. The losartan-treated group also showed
      significantly increased mean tubular diameter and interstitial area of the kidney
      (P<0.05). These results suggest that AT1 inhibition in the developing kidney
      impairs renal growth and development and modulates the expression of ALK-5 and
      TbetaRII.

PMID- 16897005
TI  - Energy homeostasis and cachexia in chronic kidney disease.
AB  - Loss of protein stores, presenting as clinical wasting, is reported to have a
      prevalence of 30-60% and is an important risk factor for mortality in chronic
      kidney disease (CKD) patients. There is debate as to whether the clinical wasting
      in CKD patients represents malnutrition or cachexia. Malnutrition results from
      inadequate intake of nutrients, despite a good appetite, and manifests as weight
      loss associated with adaptive metabolic responses such as decreased basic
      metabolic rate and preservation of lean body mass at the expense of fat mass.
      Furthermore, the abnormalities in malnutrition can usually be overcome simply by
      supplying more food or altering the composition of the diet. In contrast,
      cachexia is characterized by maladaptive responses such as anorexia, elevated
      basic metabolic rate, wasting of lean body tissue, and underutilization of fat
      tissue for energy. Diet supplementation and intradialytic parenteral nutrition
      have not been successful in reversing cachexia in CKD. The etiology of cachexia
      in CKD is complex and multifactorial. Two major factors causing muscle wasting in
      uremia are acidosis and decreased insulin responses. Inflammation secondary to
      cytokines may also play a significant role. The hypoalbuminemia of CKD patients
      is principally associated with inflammation and not changes in food intake. There
      is also recent evidence that hypothalamic neuropeptides may be important in the
      downstream signaling of cytokines in the pathogenesis of cachexia in CKD.
      Elevated circulating levels of cytokines, such as leptin, may be an important
      cause of uremia-associated cachexia via signaling through the central
      melanocortin system. Further research into the molecular pathways leading to
      cachexia may lead to novel therapeutic therapy for this devastating and
      potentially fatal complication of CKD.

PMID- 16897006
TI  - Acute effects of gentamicin on glomerular and tubular functions in preterm
      neonates.
AB  - It has been reported that gentamicin causes natriuresis, magnesuria and calciuria
      in neonates. The aim of this study was to determine the acute effects of trough
      and peak levels of gentamicin on the values of serum creatinine (SCr), urine
      albumin/urine creatinine (UA/UCr), fractional excretion of sodium and potassium
      (FENa, FEK) and urine calcium/urine creatinine (UCa/UCr) in preterm neonates
      treated with gentamicin for suspected infection. Baseline levels of serum and
      urine Cr, Na and K and urine albumin and Ca levels together with trough and peak
      gentamicin levels were measured in 61 preterm neonates at the start of the
      therapy, on the day of the third gentamicin dose and 48-72 h after the cessation
      of the gentamicin therapy. Therapeutic trough and peak levels were recorded in 56
      (91.8%) and 39 (63.9%) of the preterm neonates, respectively, whereas high trough
      (>2 mg/dl) and peak (>9.99 mg/dl) levels were recorded in five (8.1%) and 11
      (18%) of the 61 preterm neonates, respectively. Trough and peak levels of
      gentamicin were positively correlated with SCr, UA/UCr, FENa, FEK and UCa/UCr
      values. The UA/UCr, FENa and UCa/UCr values recorded during treatment were
      statistically significantly different from sub-therapeutic, therapeutic and high
      peak gentamicin levels. Gentamicin was found to have a serum peak level-dependent
      microalbuminuric, natriuric and calciuric effect in preterm neonates. Based on
      these results, we suggest that when the monitoring of serum gentamicin levels is
      not possible, the monitoring of UA/UCr, FENa and UCa/UCr can be useful as a
      noninvasive alternative.

PMID- 16897010
TI  - Location and variability of epicardiac ganglia in human fetuses.
AB  - The aim of the study was to determine the morphology of epicardiac ganglia in
      human fetuses at different stages of their development as these ganglia are
      considered to be of a pivotal clinical importance. Twenty-one fetal hearts were
      investigated applying a technique of histochemistry for acetylcholinesterase to
      visualize the epicardiac neural ganglionated plexus with its subsequent
      stereoscopic examination on total organs. In all of the examined fetuses,
      epicardiac neural plexus with numerous ganglia was well recognizable and could be
      clearly differentiated into seven ganglionated subplexuses, topography and
      structural organization of which were typical for hearts of adult human. The
      largest ganglion number comprising 77% of all counted ganglia was identified on
      the dorsal atrial surface. Fetal epicardiac plexus in gestation period of 15-40
      weeks contained 929 +/- 62 ganglia, but ganglion amount did vary substantially
      from heart to heart. In conclusion, this study implies that the human fetal
      epicardiac ganglia occupy their definitive location already at gestation period
      from 15 weeks and their number as well as distribution on heart surface
      presumably is not age dependent.

PMID- 16897009
TI  - Thidiazuron-induced regeneration of Echinacea purpurea L.: micropropagation in
      solid and liquid culture systems.
AB  - The goals of this study were to investigate thidiazuron (TDZ)-induced
      morphogenesis of Echinacea purpurea L. and to assess the possibility of
      developing a liquid-based protocol for rapid micropropagation. Callus development
      and root organogenesis were observed on leaf explants cultured on media
      containing 2,4-dicholorophenoxyacetic acid or dicamba, but no plantlets were
      regenerated. Addition of TDZ to the culture medium as the sole growth regulator
      resulted in the production of regenerable callus cultures. The highest rate of
      regeneration was observed for explants cultured on medium with TDZ at 2.5 microM
      or higher. Tissue derived from 1.0 microM TDZ treatments was used to initiate
      liquid cultures. All liquid treatments produced a similar number of regenerants
      but significantly more healthy plants were obtained from cultures grown in the
      presence of 0.1 and 1.0 microM TDZ. This TDZ-based micropropagation system is the
      first liquid, large-scale propagation protocol developed for the mass production
      of E. purpurea plants.

PMID- 16897011
TI  - WITHDRAWN: Immunohistochemical localization of Ih channel HCN3 in the rat brain.
AB  - Ahead of Print article withdrawn by publisher

PMID- 16897007
TI  - Predictors and outcome of catheter-related bacteremia in children on chronic
      hemodialysis.
AB  - Tunneled central venous catheters are often used in children on chronic
      hemodialysis. This study was done to evaluate the spectrum of catheter-related
      bacteremia (CRB) and to determine predictors of recurrent CRB in children on
      hemodialysis. Chart review was performed in 59 children from a pediatric dialysis
      unit with chronic, tunneled, cuffed hemodialysis catheters between January 1999
      and December 2003. CRB was diagnosed in 48 of 59 (81%) patients. The incidence of
      CRB was 4.8/1,000 catheter days. Overall catheter survival (290+/-216 days) was
      significantly longer than infection-free catheter survival (210+/-167 days,
      p<0.05). Organisms isolated were gram-positive in 67%, gram-negative in 14%, and
      polymicrobial in 19%. Systemic antibiotics cleared CRB in 34% and an additional
      23% cleared with the inclusion of antibiotic-heparin locks; 43% required catheter
      exchange. There was a significant likelihood of early catheter exchange with
      polymicrobial CRB (p<0.01). Catheter loss occurred from infection in 63%. Risk
      factors for CRB included young age (<10 years) and presence of human
      immunodeficiency virus (HIV) infection. Patients with >2 initial positive blood
      cultures (p<0.0001) had a significantly higher rate of recurrence after 6 weeks
      of initial treatment. In conclusion, CRB remains a major determinant of catheter
      loss. However, overall catheter survival is longer than infection-free catheter
      survival, suggesting that systemic antibiotics with antibiotic-heparin locks
      should be the initial step in the management of CRB and this approach may salvage
      some catheters.

PMID- 16897012
TI  - Spatial growth and pattern formation in the small intestine microvascular bed
      from larval to adult Xenopus laevis: a scanning electron microscope study of
      microvascular corrosion casts.
AB  - The microvascular anatomy of the small intestine of metamorphosing tadpoles of
      the South African Clawed Toad, Xenopus laevis (Daudin) is studied from
      developmental stages 55 to 65 and in adults by scanning electron microscopy (SEM)
      of vascular corrosion casts (VCCs) and light microscopy. Up to stage 62, VCCs
      reveal a dense two-dimensional vascular network ensheating the intestinal tube,
      whose proximal portion forms a clockwise spiralling outer and its distal portion
      an anti-clockwise spiralling inner coil. Vessels of the intestinal network impose
      flat and run circularly to slightly obliquely. Locally, dense capillary plexus
      with small "holes" indicating ongoing intussusceptive microvascular growth (IMG)
      and vessel maturation, are present. The typhlosole, an invagination along the
      proximal portion of the small intestine, reveals a dense capillary bed with
      locally ongoing IMG. VCCs of stages 62/63 for the first time reveal a three
      dimensional vascular bed with longitudinal intestinal folds of varying size and
      heights greatly enlarging the luminal exchange area of the intestinal tube. From
      stage 65 onwards, longitudinal intestinal folds undulate and, though smaller in
      size and less mature as indicated in VCCs by the presence of wider, sinus-like
      vessels with small "holes" interposed between, closely resemble the intestinal
      folds present in the small intestine of adult Xenopus. Our data suggest that
      maturation of the vascular pattern in the small intestine of X. laevis tadpoles
      takes place successively after stages 62-63, and growth during this period is
      preferentially by intussusception.

PMID- 16897013
TI  - The minimum effort required to eradicate infections in models with backward
      bifurcation.
AB  - We study an epidemiological model which assumes that the susceptibility after a
      primary infection is r times the susceptibility before a primary infection. For r
      = 0 (r = 1) this is the SIR (SIS) model. For r > 1 + (mu/alpha) this model shows
      backward bifurcations, where mu is the death rate and alpha is the recovery rate.
      We show for the first time that for such models we can give an expression for the
      minimum effort required to eradicate the infection if we concentrate on control
      measures affecting the transmission rate constant beta. This eradication effort
      is explicitly expressed in terms of alpha,r, and mu As in models without backward
      bifurcation it can be interpreted as a reproduction number, but not necessarily
      as the basic reproduction number. We define the relevant reproduction numbers for
      this purpose. The eradication effort can be estimated from the endemic steady
      state. The classical basic reproduction number R0 is smaller than the eradication
      effort for r > 1 + (mu/alpha) and equal to the effort for other values of r. The
      method we present is relevant to the whole class of compartmental models with
      backward bifurcation.

PMID- 16897014
TI  - High frequency spikes in long period blood cell oscillations.
AB  - Several hematological diseases are characterised by oscillations of various blood
      cell populations. Two of these are a variant of chronic myelogenous leukemia
      (CML) and cyclical neutropenia (CN). These oscillations typically have long
      periods ranging from 20 to 60 days, despite the fact that the stem cell cycling
      time is thought to be of the order of 2-3 days. Clinical data from humans and
      laboratory data from the grey collie animal model of CN is suggestive of the idea
      that these long period oscillations may also contain higher frequency spiky
      oscillations. We show how such oscillations can be understood in the context of
      slow periodic stem cell oscillations, by analysing a two component differential
      delay equation model of stem cell and neutrophil populations.

PMID- 16897016
TI  - Modelling parasitism and predation of mosquitoes by water mites.
AB  - Parasitism and predation are two ecological interactions that can occur
      simultaneously between two species. This is the case of Culicidae (Insecta:
      Diptera) and water mites (Acari: Hydrachnidia). The larva mites are~parasites of
      aquatic and semiaquatic insects, and deutonymphs and adults are predators of
      insect larvae and eggs. Since several families of water mites are associated with
      mosquitoes there is an interest in the potential use of these mites as biological
      control agents. The aim of this paper is to use mathematical modelling and
      analysis to assess the impact of predation and parasitism in the mosquito
      population. We propose a system of ordinary differential equations to model the
      interactions among the larval and adult stages of mosquitoes and water mites. The
      model exhibits three equilibria: the first equilibrium point corresponds to the
      state where the two species are absent, the second one to the state where only
      mosquitoes are present (water mites need insects to complete their life cycle),
      and the third one is the coexistence equilibrium. We analyze conditions for the
      asymptotic stability of equilibria, supported by analytical and numerical
      methods. We discuss the different scenarios that appear when we change the
      parasitism and predation parameters. High rates of parasitism and moderate
      predation can drive two species to a stable coexistence.

PMID- 16897015
TI  - Cell-cell communication by quorum sensing and dimension-reduction.
AB  - Several bacterial taxa change their behavior if the population density exceeds a
      certain threshold. This phenomenon is the consequence of a communication system
      between the bacteria and is called quorum sensing (QS). Up to now, this
      phenomenon is mostly modeled at population level. However, new experimental
      techniques allow for single cell analysis. We introduce a modeling approach for
      the description of this QS system, including a discussion of the regulatory
      network and its bistable behavior. Based on this single-cell model we develop and
      analyze a spatially structured model for a cell population. Special attention is
      given to the scaling behavior w.r.t. the cell size (leading to an approximation
      theorem for stationary solutions) and its consequences for the interpretation of
      cell communication (QS versus diffusion sensing). Concluding, we apply the
      modeling approach to spatially structured experimental data.

PMID- 16897017
TI  - Mathematical model of nitric oxide convection and diffusion in a renal medullary
      vas rectum.
AB  - In this study, the generation, convection, diffusion, and consumption of nitric
      oxide (NO) in and around a single renal medullary descending or ascending vas
      rectum in rat were modeled using CFD. The vascular lumen (with a core RBC-rich
      layer and a parietal layer), the endothelium, the pericytes and the interstitium
      were represented as concentric cylinders. We accounted for the generation of NO
      by vascular endothelial cells, and that by the epithelial cells of medullary
      thick ascending limbs (mTALs) and inner medullary collecting ducts (IMCDs), the
      latter via interstitial boundary conditions. Luminal velocity profiles were
      obtained by modeling blood flow dynamics. Our results suggest that convection
      (i.e., blood flow per se) does not significantly affect NO concentrations along
      the cortico-medullary axis, because the latter are mostly determined by the rate
      of NO production and that of NO consumption by hemoglobin. However, the shear
      stress-mediated effects of blood flow on NO generation rates, and therefore NO
      concentrations, were predicted to be important. Finally, we found that unless
      epithelial NO generation rates (per unit tubular surface area) are at least 10
      times lower than endothelium NO generation rates, NO production by mTALs and
      IMCDs affects vascular NO concentrations, with possible consequences for
      medullary blood flow distribution.

PMID- 16897018
TI  - [Renal replacement therapy in the intensive care unit].
AB  - Acute renal failure in critically ill patients in the intensive care unit is
      associated with high morbidity and mortality which is independent of the
      underlying etiology. Despite improvements in intensive care medicine and renal
      replacement therapy, patients with acute renal failure have much higher morbidity
      and mortality rates than patients without acute renal failure in the intensive
      care unit. In this overview, we summarize the literature on the incidence and
      mortality of patients with acute renal failure in the intensive care unit.
      Furthermore, we discuss timing of the initiation of renal replacement therapy,
      patient outcome with different renal replacement therapies and the adequate
      dialysis dose to be delivered.

PMID- 16897019
TI  - [Long QT syndrome].

PMID- 16897020
TI  - [Detection of intraoperative awareness via auditory evoked potentials in an
      infant].
AB  - Intraoperative wakefulness is not only limited to adults and can also be found at
      a similar percentage (0.8%) in paediatric anaesthesia. For prevention of
      awareness neurophysiologic methods like auditory evoked potentials might be
      helpful. We report a case of a 2-year-old boy receiving balanced anaesthesia with
      sevoflurane and alfentanil. Midlatency auditory evoked potentials (MLAEPs) were
      recorded continuously before, during and after the surgical procedure. During the
      surgical procedure sevoflurane was withdrawn unintentionally. After a short
      period of time the boy started coughing and moved his legs, which was interpreted
      as insufficient analgesia. Several boli of alfentanil did not lead to the
      expected clinical effect on the depth of anaesthesia. After a recheck of the
      anaesthetic ventilator the error was determined and delivery of the volatile
      anaesthetic restored. The postoperative evaluation of the MLAEPs revealed the
      inadequate suppression of auditory processing during this incident with latencies
      comparable to the awake state. After reapplication of sevoflurane the MLAEPs were
      almost completely suppressed demonstrating adequate anesthetic depth. Exemplarily
      this case suggests that MLAEPs could be used to detect intraoperative awareness
      also in paediatric anaesthesia. Investigations to prove the validity and
      reproducibility of MLAEPs in children will be necessary.

PMID- 16897021
TI  - [2020 trauma surgery--a strategic perspective].

PMID- 16897022
TI  - [Arthroscopic reconstruction of the rotor cuff].
AB  - Over the last years treatment of rotator cuff tears is evolving gradually from
      open to complete arthroscopic repair. There had been fast developments in
      arthroscopic techniques and instruments and there is a better understanding of
      biomechanical backgrounds. For a good clinical outcome it is not necessary to
      obtain a watertight closure in all cases but to balance the force couples in the
      coronal and transverse plane. There is recent discussion regarding the optimum
      techniques and stitches for cuff reconstruction and resulting developments in
      this field. To determine the individual reconstruction technique it is crucial to
      recognize the different tear categories. Based on these findings we are now able
      to treat nearly every cuff tear arthroscopically, even a retracted massive
      lesion.

PMID- 16897023
TI  - [Sacroplasty for the treatment of sacral insufficiency fractures].
AB  - Sacral insufficiency fractures are an easily overlooked injury of the elderly,
      leading to severe and debilitating low back pain. Percutaneous vertebroplasty
      with polymethylmethacrylate (PMMA) has become the treatment of choice for painful
      osteoporotic vertebral compression fractures. This is mainly due to the excellent
      results in pain relief, combined with a low morbidity of the procedure and the
      possibility of performing it in an outpatient setting. This well-known technique
      can be transferred to the treatment of sacral insufficiency fractures for which
      no active therapy is currently available. This so-called sacroplasty was first
      reported in 2002 as a single case report. Six other cases with this indication
      have been reported in the Anglo-American literature so far. This article is the
      first description of this technique in the German literature. It comprises the
      description of two typical cases highlighting the difficulties in diagnosis,
      surgical technique, and possible complications. Both patients were treated
      successfully and had a dramatic pain relief within several hours.

PMID- 16897024
TI  - [Computer-assisted screw placement into the posterior pelvic ring: assessment of
      different navigated procedures in a cadaver trial].
AB  - OBJECTIVE: Computer-assisted procedures have recently been introduced for
      navigated iliosacral screw placement. Currently there are only few data available
      reflecting results and outcome of the different navigated procedures which may be
      used for this indication. We therefore evaluated the features of a new 3D image
      intensifier used for navigated iliosacral screw placement compared to 2D
      fluoroscopic and CT navigation. MATERIALS AND METHODS: Twenty fixed human
      cadavers were used in this trial. Cannulated cancellous screws were
      percutaneously implanted in the supine position in four treatment groups. An
      optoelectronic system was used for the navigated procedures. Screw placement was
      postoperatively assessed by fluoroscopic 3D scan and CT. The target parameters of
      this investigation were practicability, precision as well as procedure and
      fluoroscopic time per screw. RESULTS: All navigated procedures revealed a
      significant loss of time compared to non-navigated screw placement (2D: p<0.001,
      3D: p>0.05, CT: p<0.001). Simultaneously a significant decrease of radiation
      exposure time was observed in the navigated groups (p<0.001 each). The
      misplacement rate was 20% in the non-navigated and the 2D fluoroscopic navigated
      group each. Procedures providing 3D imaging of the posterior pelvis did not
      produce any screw misplacement (p>0.05). However, the CT procedure was associated
      with time-consuming registration and high rates of failed matching procedures.
      CONCLUSION: Our data show a clear benefit of using C-arm navigation for
      iliosacral screw placement compared with the CT-based procedure. While both
      fluoroscopy-based navigation procedures decrease intraoperative radiation
      exposure times, only 3D fluoroscopic navigation seems to improve the precision
      compared to non-navigated screw placement.

PMID- 16897025
TI  - [What to do if incompressible bleeding from a stab wound occurs in EMS and ER?
      Temporary control with a Foley catheter].
AB  - Exsanguination plays a key role in avoidable prehospital deaths. As some
      bleedings from deep stab wounds cannot be stopped with direct compression, the
      insertion of a Foley catheter can prevent ongoing bleedings. A case report of
      bleeding from a stab wound in the supraclavicular region is given. The simple
      measure of careful insertion and blocking of a Foley catheter proved to be a key
      resuscitative procedure which can be done under any suitable circumstances.

PMID- 16897026
TI  - [Patient- and hospital-related determinants of satisfaction with hospital stay of
      severely injured patients].
AB  - BACKGROUND: General political and legal changes in the German health care system
      will increase the importance of patient surveys. Patient satisfaction with
      medical and organizational care during their stay in a hospital is a relevant
      outcome of quality assurance. Satisfied patients also show a higher compliance
      with treatment and therefore increase the probability of a successful outcome.
      The objective of this analysis was to identify determinants of satisfaction with
      hospital stay of severely injured patients. METHODS: A written questionnaire was
      sent to 121 severely injured patients, who were predominantly hurt by traffic or
      work-related accidents and were treated between 1996 and 2001 in two hospitals in
      Cologne (response rate=74.4%, n=90). The questionnaire used in this study
      contained questions about psychosocial care of physicians and nurses in and
      organizational and structural characteristics of the hospital. RESULTS: Logistic
      regressions identified two significant predictors for satisfaction with hospital
      stay: (1) subjective evaluation of psychosocial quality of care by physicians and
      (2) patients' perception of active integration in treatment decisions.
      CONCLUSION: The results of this analysis confirm the importance of soft science
      in medical education also for surgeons. Medical education should integrate
      knowledge about psychosocial aspects of medicine. The quality of psychosocial
      care of physicians seems to be a predictor of patient satisfaction. The
      probability of dissatisfaction increases with deficits in communication,
      information, and time as well as no active integration in treatment. The results
      of this analysis confirm the vital importance of psychosocial aspects in
      physician-patient interactions with severely injured patients for satisfaction
      with stay in hospital.

PMID- 16897027
TI  - [Operative treatment of proximal humeral fractures with helix wire].
AB  - BACKGROUND: Between 1 January 2000 and 31 December 2002, a total of 50 patients
      with a dislocated or unstable fracture of the proximal humerus were treated
      surgically with a titanium helix wire introduced retrogradely into the medullary
      cavity. MATERIAL AND METHODS: Fracture classification showed 8 cases of a two
      fragment fracture, 32 cases of a three-fragment fracture, and 10 cases of a so
      called four-fragment fracture. A retrospective radiographic and medical review of
      all 50 patients showed postoperative complications in 24% of the cases; in 8
      cases (16%) secondary loss of retention occurred with consecutive projection of
      the helix wires into the subacromial joint space. There were two cases each (4%)
      of perforation of the helix wire into the joint space without loss of retention
      and fracture dehiscence because of a blocking mechanism by the helix wire in the
      subcapital fracture gap. The postoperative revision rate was 18% (9/50) as a
      result. Of 50 patients with a titanium helix wire, 38 (76%) were reviewed after
      an average of 23 months (12-31). Radiologically partial necrosis of the head of
      the humerus was seen in two patients and there was necrosis of the head of the
      humerus with pseudarthrosis in one patient, which had a negative effect on the
      Constant score. RESULTS: Because of a change of procedure (n=5) and intercurrent
      deaths (n=5) only 2 of 12 patients, in whom complications had occurred
      postoperatively, could be followed up clinically; the results of the follow-up
      are sure to be distorted by this selection effect. Of 38 patients, 32 (84%)
      showed very good to good results functionally; the average Constant score was 74
      points and the average age- and sex-specific corrected score was 92%. DISCUSSION:
      Thus, the procedure does not achieve better functional results compared to other
      rigid and semirigid internal fixation methods while it has a high complication
      and revision rate compared to other rigid and semirigid internal fixation
      methods. Moreover, early functional treatment is not possible so that the
      titanium helix wire represents a retention aid rather than stable internal
      fixation. Overall we cannot recommend the procedure for the operative management
      of proximal humerus fractures further and have abandoned it ourselves.

PMID- 16897028
TI  - [Surgical management of spondylodiscitis. An analysis of 78 cases].
AB  - Spondylodiscitis is a rare bacterial infection of the spine with an inflammatory,
      destructive course. To obtain further information on the therapeutic management
      and clinical course of spondylodiscitis, we retrospectively investigated 78
      patients after surgical intervention. Mean age was 64 years (+/-4.6 years; range
      21-80 years), the mean length of stay 49 days (+/-8.2 days; 3-121 days) including
      24 days (+/-4.7 days; 0-112 days) in ICU. In hospital mortality was 9%. The
      cervical spine was affected in 10%, the thoracic spine in 35% and the
      lumbar/sacral spine in 55% of patients. Abscess formation occurred in 65% and
      destruction of the vertebral body in 74%. A total of 75% of patients presented
      with neurological deficits which could be improved by surgical intervention in
      82% of cases. 24 patients were treated by ventral debridement and stabilization
      alone, 20 patients with a combined dorsoventral method. Most patients (n=34) were
      stabilized via dorsal bridging instrumentation without ventral debridement of the
      focus. Of this group, 23 patients were initially scheduled for secondary ventral
      debridement but complete healing was achieved prior to this, so further surgical
      therapy was unnecessary. Successful cure was obtained in 92% of cases. Based on
      our findings, we favor a split surgical approach: initially with dorsal internal
      fixation only. Abscesses can be drained percutaneously. Ventral debridement and
      stabilization is only recommended if insufficient stability can be obtained by
      dorsal fixation alone, as shown by the persistence of infection or pain.

PMID- 16897029
TI  - [Care of polytrauma and the conflict between "acting and omitting". Medical,
      ethical and legal aspects in the current debate on the legal validity of patient
      directives].
AB  - When treating the seriously injured, physicians are called upon to take into
      account not only what is medically possible, but also what is ethically and
      legally viable. This results in an area of conflict between 'acting and
      omitting', in which medical actions have to be weighed up and justified with
      regard to the individual diagnosis, prognosis and will of the patient. In this
      paper the medical, ethical and legal aspects of this problematic area are
      illustrated using a case example, and placed in the context of the current debate
      on the legal validity of the extent and liability of advance patient directives.

PMID- 16897030
TI  - [The modular MML revision system in knee revision and tumor arthroplasty].
AB  - Increasing age and a higher level of mobility lead to an increasing incidence in
      revision arthroplasty after total knee replacement and tumor surgery. So far, the
      reconstruction of large defects in bony and soft tissue environments can be
      accomplished by the modern modular components of revision implants. The
      consecutive reconstruction of the extensor mechanism in extended revision has its
      own drawbacks and is often associated with significant functional limitations for
      the patient. Specially designed implants and methods are required to generate
      good functional results. The modular knee revision system MML provides specific
      modifications of the tibial component for reconstruction of the extensor
      mechanism. Combined with artificial strips, an excellent functional outcome could
      be achieved. In this study, 70 patients were operated with the MML endoprosthesis
      in knee revision or tumor surgery. An excellent functional outcome could be
      determined. At 7 years after surgery, an average of 32+/-13 points was achieved
      on the Oxford Knee Score. The outcome measurement using the functional scoring
      system of the American Knee Society (AKS score) showed similarly good results
      with 71+/-25 points out of 100. A minor deficit of only 2 degrees in active
      extension could be observed after reconstruction of the extensor mechanism. In
      conclusion, we have demonstrated that the MML modular revision system is
      appropriate for reconstruction of segmental bone defects.

PMID- 16897031
TI  - Evidence for estrogen receptor alpha and beta expression in skeletal muscle of
      pigs.
AB  - Recent research suggests that estrogen receptors (ERs) are of significance in
      skeletal muscle function. The aim of the present study was to investigate,
      whether ERalpha and ERbeta are expressed in different porcine skeletal muscles
      and in satellite cells derived from semimembranosus muscle (SM) at the protein
      and mRNA level. Immunohistochemistry demonstrated positive staining for ERalpha
      in the nuclei of skeletal muscle cells, while the ERbeta stain showed positive
      signals in nuclei and cytoplasm of skeletal myofibers and myoblasts derived from
      satellite cells. Additionally, a weak expression of both ER subtypes was seen in
      skeletal muscle tissue and SM satellite cells with Western blot analysis. A clear
      expression of the ERalpha mRNA and a weak expression of the ERbeta mRNA was seen
      in skeletal muscle tissue and SM satellite cell cultures, as determined by
      reverse transcription (RT)-PCR. The present study shows for the first time that
      both ERalpha and ERbeta are expressed in porcine skeletal muscle, which,
      consequently, could be considered as a target tissue for estrogens or estrogen
      like compounds. However, more detailed studies on the functional impact of both
      receptor subtypes in skeletal muscle are necessary. The porcine SM satellite cell
      culture provides a suitable in vitro model to investigate estrogenic effects on
      pig skeletal muscle.

PMID- 16897032
TI  - Negative control of the high light-inducible hliA gene and implications for the
      activities of the NblS sensor kinase in the cyanobacterium Synechococcus
      elongatus strain PCC 7942.
AB  - The hliA gene of the cyanobacterium Synechococcus elongatus PCC 7942 is known to
      be upregulated by high-intensity light through the activity of the NblS sensor
      kinase. In this work it was found that, within the hliA upstream region, changes
      to the sequence around -30 to -25 (relative to the transcriptional start site)
      resulted in elevated hliA expression, implicating this region in negative
      regulation of the gene. Electrophoretic mobility shift assays performed were
      consistent with a protein binding this region that acts to keep the gene off in
      lower light. A reduction in gene dosage of nblS in vivo resulted in enhanced hliA
      expression, suggesting that negative control of hliA is mediated through NblS. An
      extended version of the high light regulatory 1 (HLR1) motif (previously
      described in Synechocystis PCC 6803) was identified within the sequence
      surrounding -30 to -25 of hliA. The extended HLR1 sequence was found upstream of
      other NblS-controlled genes from S. elongatus and Synechocystis PCC 6803 and
      upstream of hli genes from a variety of cyanobacterial and related genomes. These
      results point to the evolutionary conservation of the HLR1 element and its
      importance in NblS-mediated signaling and yield new insight into NblS-mediated
      control of gene expression.

PMID- 16897033
TI  - Oxidative inactivation of reduced NADP-generating enzymes in E. coli: iron
      dependent inactivation with affinity cleavage of NADP-isocitrate dehydrogenase.
AB  - Treatment of E. coli extract with iron/ascorbate preferentially inactivated NADP
      isocitrate dehydrogenase without affecting glucose-6-phosphate dehydrogenase.
      NADP-Isocitrate dehydrogenase required divalent metals such as Mg(2+), Mn(2+ )or
      Fe(2+) ion. Iron/ascorbate-dependent inactivation of the enzyme was accompanied
      with the protein fragmentation as judged by SDS-PAGE. Catalase protecting the
      enzyme from the inactivation suggests that hydroxyl radical is responsible for
      the inactivation with fragmentation. TOF-MS analysis showed that molecular masses
      of the enzyme fragments were 36 and 12, and 33 and 14 kDa as minor components.
      Based on the amino acid sequence analyses of the fragments, cleavage sites of the
      enzyme were identified as Asp307-Tyr308 and Ala282-Asp283, which are presumed to
      be the metal-binding sites. Ferrous ion bound to the metal-binding sites of the
      E. coli NADP-isocitrate dehydrogenase may generate superoxide radical that forms
      hydrogen peroxide and further hydroxyl radical, causing inactivation with peptide
      cleavage of the enzyme. Oxidative inactivation of NADP-isocitrate dehydrogenase
      without affecting glucose 6-phosphate dehydrogenase shows only a little influence
      on the antioxidant activity supplying NADPH for glutathione regeneration, but may
      facilitate flux through the glyoxylate bypass as the biosynthetic pathway with
      the inhibition of the citric acid cycle under aerobic growth conditions of E.
      coli.

PMID- 16897034
TI  - The synthesis and role of the mechanosensitive channel of large conductance in
      growth and differentiation of Bacillus subtilis.
AB  - A translational lacZ fusion of the Bacillus subtilis mscL gene that encodes the
      mechanosensitive channel of large conductance (MscL) was expressed at significant
      levels during log phase growth of B. subtilis, and the level of mscL-lacZ
      expression was increased 1.5-fold by growth in medium with high salt (1 M NaCl).
      However, in growth media with either low or high salt, mscL-lacZ expression fell
      drastically beginning in the late log phase of growth, and fell to even lower
      levels during sporulation, although a significant amount of beta-galactosidase
      from mscL to lacZ was accumulated in the developing spore. Deletion of mscL had
      no effect on B. subtilis growth, sporulation or subsequent spore germination. The
      DeltamscL strain also grew as well as the wild-type parental strain in medium
      with 1.2 M NaCl. While log phase wild-type cells grown with 1.2 M NaCl survived a
      rapid 0.9 M osmotic downshift, log phase DeltamscL cells rapidly lost viability
      and lysed when subjected to this same osmotic downshift. However, by the early
      stationary phase of growth, DeltamscL cells had become resistant to a 0.9 M
      osmotic downshift.

PMID- 16897035
TI  - Expression and characterization of the assimilatory NADH-nitrite reductase from
      the phototrophic bacterium Rhodobacter capsulatus E1F1.
AB  - A nas gene region from Rhodobacter capsulatus E1F1 containing the putative nasB
      gene for nitrite reductase was previously cloned. The recombinant His(6)-NasB
      protein overproduced in E. coli showed nitrite reductase activity in vitro with
      both reduced methyl viologen and NADH as electron donors. The apparent K ( m )
      values for nitrite and NADH were 0.5 mM and 20 microM, respectively, at the pH
      and temperature optima (pH 9 and 30 degrees C). The optical spectrum showed
      features that indicate the presence of FAD, iron-sulfur cluster and siroheme as
      prosthetic groups, and nitrite reductase activity was inhibited by sulfide and
      iron reagents. These results indicate that the phototrophic bacterium R.
      capsulatus E1F1 possesses an assimilatory NADH-nitrite reductase similar to that
      described in non-phototrophic organisms.

PMID- 16897036
TI  - Characterization of the type III export signal of the flagellar hook scaffolding
      protein FlgD of Escherichia coli.
AB  - Transport of flagellar structural proteins beyond the cytoplasmic membrane is
      accomplished by a type III secretory pathway [flagellar type III secretion system
      (fTTSS)]. The mechanism of substrate recognition by the fTTSS is still enigmatic.
      Using the hook scaffolding protein FlgD of Escherichia coli as a model substrate,
      it is demonstrated that the export signal is contained within the N-terminal 71
      amino acids of FlgD. Analysis of frame-shift mutations and alterations of the
      nucleotide sequence suggest a proteinaceous nature of the signal. Furthermore,
      the physicochemical properties of the first about eight amino acids are crucial
      for export.

PMID- 16897037
TI  - Cloning, expression and deletion of the cuticle-degrading protease BLG4 from
      nematophagous bacterium Brevibacillus laterosporus G4.
AB  - Brevibacillus laterosporus G4, which was isolated from soil sample, kills free
      living nematodes (Panagrellus redivius) and plant-parasite nematodes
      (Bursaphelenchus xylophilus) and degrades their cuticle in previous bioassay. Our
      works for B. laterosporus G4 had demonstrated that an extracellular alkaline
      protease BLG4 played a key role as a pathogenic factor in infection against
      nematode. In this study, the nematicidal activity of BLG4 was further verified by
      an in vitro assay with purified recombinant BLG4. The encoding gene of BLG4 was
      cloned and showed high degree of homology with the subtilisin subclass of serine
      protease gene and another reported cuticle-degrading protease gene from
      nematophagous bacterium Bacillus sp. B16. Deletion of BLG4 by homologous
      recombinant had a significant effect on the pathogenicity of B. laterosporus. In
      infection assays the BLG4-deficient strain (BLG4-6) lost about 50% of its
      nematocidal activity and in toxicity tests the mortality rate of nematodes
      decreased with approximately 56% in comparison to wild-type strain. This is the
      first report analyzing the function of a subtilisin enzyme involved in bacterium
      against nematode at the molecular level, and it is possible to use B.
      laterosporus as a model to study host-parasite interaction and to gain detailed
      knowledge of the infection process.

PMID- 16897038
TI  - Is BMR repeatable in deer mice? Organ mass correlates and the effects of cold
      acclimation and natal altitude.
AB  - Basal metabolic rate (BMR) is probably the most studied aspect of energy
      metabolism in vertebrate endotherms. Numerous papers have explored its mass
      allometry, phylogenetic and ecological relationships, and ontogeny. Implicit in
      many of these studies (and explicit in some) is the view that BMR responds to
      selection, which requires repeatability and heritability. However, BMR is highly
      plastic in response to numerous behavioral and environmental factors and there
      are surprisingly few data on its repeatability. Moreover, the mechanistic
      underpinnings of variation in BMR are unclear, despite considerable research. We
      studied BMR repeatability in deer mice (Peromyscus maniculatus) across intervals
      of 30-60 days, and also examined the influence of birth altitude (3,800 m versus
      340 m) and temperature acclimation (to approximately 5 or approximately 20
      degrees C) on BMR, and the relationship between BMR and organ size. Neither
      acclimation temperature nor natal altitude alone influenced BMR, but the
      combination of birth at high altitude and cold acclimation significantly
      increased BMR. Few visceral organ masses were correlated to BMR and most were
      inconsistent across natal altitudes and acclimation temperatures, indicating that
      no single organ 'controls' variation in BMR. In several treatment groups, the
      mass of the 'running motor' (combined musculoskeletal mass) was negatively
      correlated to BMR and the summed mass of visceral organs was positively
      correlated to BMR. We found no repeatability of BMR in any treatment group. That
      finding-in sharp contrast to high repeatability of BMR in several other small
      endotherms-suggests little potential for direct selection to drive BMR evolution
      in deer mice.

PMID- 16897040
TI  - Identification of the human liver UDP-glucuronosyltransferase involved in the
      metabolism of p-ethoxyphenylurea (dulcin).
AB  - Dulcin (DL), now banned, was once a widely used artificial sweetener. DL
      possesses an ureido group that is metabolized by direct glucuronidation in rabbit
      liver microsomes. Dulcin N-glucuronide (DNG) is the only type of ureido N
      glucuronide known to date; ureido glucuronidation in humans has not been
      previously reported. Accordingly, the glucuronidation of DL was studied using
      human liver microsomes (HLM) and expressed human UDP-glucuronosyltransferase
      (UGT) enzymes. The average K (m) and V (max) values from nine HLM samples were
      2.10 mM and 0.156 nmol/mg/min, respectively. Of the six human UGT isoforms
      screened for their ability to glucuronidate DL, only UGT1A1 and UGT1A9 showed
      activity. The apparent K (m) values using UGT1A1 and UGT1A9 were 5.06 and 6.99
      mM, and the apparent V (max) values were 0.0461 and 0.106 nmol/min/mg,
      respectively. Phenolphthalein, a substrate for UGT1A9, inhibited DL
      glucuronidation in HLM competitively (K (i) = 0.356 mM), but bilirubin, a
      substrate for UGT1A1, did not. These results suggest that UGT1A9 is a key enzyme
      catalyzing the glucuronidation of DL.

PMID- 16897039
TI  - Neutron Laue macromolecular crystallography.
AB  - Recent progress in neutron protein crystallography such as the use of the Laue
      technique and improved neutron optics and detector technologies have dramatically
      improved the speed and precision with which neutron protein structures can now be
      determined. These studies are providing unique and complementary insights on
      hydrogen and hydration in protein crystal structures that are not available from
      X-ray structures alone. Parallel improvements in modern molecular biology now
      allow fully (per)deuterated protein samples to be produced for neutron scattering
      that essentially eradicate the large-and ultimately limiting-hydrogen incoherent
      scattering background that has hampered such studies in the past. High quality
      neutron data can now be collected to near atomic resolution (approximately 2.0 A)
      for proteins of up to approximately 50 kDa molecular weight using crystals of
      volume approximately 0.1 mm3 on the Laue diffractometer at ILL. The ability to
      flash-cool and collect high resolution neutron data from protein crystals at
      cryogenic temperature (15 K) has opened the way for kinetic crystallography on
      freeze trapped systems. Current instrument developments now promise to reduce
      crystal volume requirements by a further order of magnitude, making neutron
      protein crystallography a more accessible and routine technique.

PMID- 16897041
TI  - Effect of co-exposure to lead and cadmium on antioxidant status in rat ovarian
      granulose cells.
AB  - The effects of combined exposure to lead and cadmium on granulose cells were
      studied. Adult female rats were treated i.p. with either lead acetate (LA) or
      cadmium acetate (CA) both, alone, or in combination at a dose of 0.05 mg/kg body
      weight on a daily basis for 15 days. Both metals were accumulated in the ovary
      after metal exposure. Metal exposure caused a decrease in reduced glutathione
      content along with elevated lipid peroxidation in all groups. Granulose cells of
      both cadmium as well as combination group demonstrated a maximum increase in
      lipid peroxides and catalase activity, along with decreased glutathione status
      and superoxide dismutase activities. Combined treated animals exhibited an
      intermediate effect in antioxidant status. However, "in vitro" exposure showed no
      significant change in antioxidant enzymes in all metal exposed cells. Data from
      the present study indicates that lead and cadmium in isolation and in combination
      cause oxidative stress. Lead and cadmium in combination do not show additive or
      synergistic effect indicating the competition between them due to similarity in
      electronic affinities. Present study highlights the effects of toxic metals that
      disturb membrane integrity of cells via ROS and thereby classifying mechanism for
      altered receptor binding, steroidogenesis, and hormone production.

PMID- 16897042
TI  - Use it or lose it: molecular evolution of sensory signaling in primates.
AB  - Sensory organs provide key and, in many cases, species-specific information that
      allows animals to effectively forage, find mates, and avoid hazards. The primary
      sensors for the vertebrate senses of vision, taste, and smell are G-protein
      coupled receptors (GPCRs) expressed by sensory receptor cells that initiate
      intracellular signal transduction cascades in response to activation by
      appropriate stimuli. The identification of sensory GPCRs and their related
      downstream transduction components from a variety of species has provided an
      essential tool for understanding the molecular evolution of sensory systems.
      Expansion of the number of genes encoding sensory GPCRs has, in some cases,
      expanded the repertoire of signals that animals detect, allowing them to occupy
      new niches, while, in other cases, evolution has favored a reduction in the
      repertoire of receptors and their cognate signal transduction components when
      these signals no longer provide a selective advantage. This review will focus on
      recent studies that have identified molecular changes in vision, smell, taste,
      and pheromone detection during primate evolution.

PMID- 16897044
TI  - SGK1 is not required for regulation of colonic ENaC activity.
AB  - The serum and glucocorticoid-inducible kinase SGK1 is known to be upregulated by
      mineralocorticoids and to enhance ENaC activity in several expression systems.
      Moreover, the amiloride-sensitive transepithelial potential difference in the
      collecting duct is lower in gene-targeted mice lacking SGK1 (sgk1 (-/-)) than in
      their wild-type littermates (sgk1 (+/+)). Accordingly, the ability of sgk1 (-/-)
      mice to decrease urinary sodium output during salt depletion is impaired. These
      observations highlight the importance of SGK1 in the stimulation of renal ENaC
      activity. In colonic epithelium, ENaC activity and, thus, transepithelial
      potential difference (V (te)) are similarly upregulated by mineralocorticoids.
      The present study thus explored V (te) and the apparent amiloride-sensitive
      equivalent short circuit current (I (amil)) in the colon from sgk1 (-/-) and sgk1
      (+/+) mice before and after treatment with low salt diet, the glucocorticoid
      dexamethasone [DEXA, 10 mug/g body weight (BW)], or the mineralocorticoid
      deoxycorticosterone acetate (DOCA, 1.5 mg/day). Surprisingly, V (te) and I (amil)
      were both significantly (p<0.05) higher in sgk1 (-/-) than in sgk1 (+/+)
      untreated mice. A 7-day exposure to low salt diet increased V (te) and I (amil)
      in both genotypes, but did not abrogate the differences of V (te) and I (amil)
      between sgk1 (-/-) and sgk1 (+/+) mice. Plasma aldosterone levels were
      significantly higher in sgk1 (-/-) than in sgk1 (+/+) mice both under control
      conditions and under low salt diet, which may explain the enhanced V (te) in sgk1
      (-/-) mice. Treatment with DEXA or DOCA both significantly increased V (te) and I
      (amil) in sgk1 (+/+) mice and tended to increase V (te) and I (amil) in sgk1 (-/
      ) mice. Under treatment with DEXA or DOCA, V (te) and I (amil) were similar in
      sgk1 (-/-) and sgk1 (+/+) mice. Fecal Na(+) excretion was similar in sgk1 (+/+)
      mice and in sgk1 (-/-) mice and was similarly decreased by low Na(+) diet in both
      genotypes. In conclusion, transepithelial potential and amiloride-sensitive short
      circuit current are enhanced in the colonic epithelium of SGK1-deficient mice.
      Thus, lack of SGK1 does not disrupt colonic ENaC activity and its regulation by
      salt depletion.

PMID- 16897047
TI  - [Endovascular therapy for intracranial aneurysms].
AB  - During the past 5 to 10 years, therapy for aneurysms has seen dramatic changes.
      In some centers they happened before the ISAT study, in others afterward.
      Endovascular treatment is now the method of choice for intracranial aneurysms
      whenever possible. Large centers are using it for 70-80% of aneurysms. Due to
      constant development of new interventional materials, even wide-necked aneurysms
      in practically all localizations can be treated today with very dependable
      results. The remaining aneurysms are quite difficult to treat and represent a
      great neurosurgical challenge. Despite all the technical improvements, closure is
      still not the most difficult element of the therapeutic procedure. This role is
      played by the subarachnoidal hemorrhage, which still is decisive for patient
      outcome. All related disciplines are urgently called upon to solve the unresolved
      problems as quickly and efficiently as possible through determined research.

PMID- 16897048
TI  - [Oral treatment of vitamin B12 deficiency in subacute combined degeneration].
AB  - Vitamin B12 deficiency due to malnutrition or malabsorption may lead to
      pernicious anemia and neurological disorders. Although randomized prospective
      studies have shown that pernicious anemia can be safely treated with oral vitamin
      B12 even in the absence of intrinsic factor, it is still common practice to treat
      patients with neurological symptoms with intramuscular cyancobalamin injections.
      We report the successful oral treatment of subacute combined degeneration of the
      spinal cord in a 24-year-old woman closely monitored clinically with MRI and
      plasma levels of vitamin B12, homocysteine, and methylmalonic acid. We suggest
      monitored oral substitution therapy as first-line therapy for neurological
      disorders related to vitamin B12 deficiency.

PMID- 16897045
TI  - [Hand-foot syndrome with capecitabine therapy].
AB  - A 72-year-old patient with esophageal carcinoma developed a severe hand-foot
      syndrome during second-line therapy with the oral fluoropyrimidine capecitabine.
      We also summarize the current knowledge with regard to the hand-foot syndrome and
      distinguish it from palmoplantar erythrodysesthesia.

PMID- 16897046
TI  - [Clinical treatment and therapy for dissected cervicocerebral artery].
AB  - Dissection of a cervicocerebral artery (CAD) is the second leading cause of
      stroke at younger ages. The pathogenesis of spontaneous CAD is not fully
      clarified. Defective connective tissue components may cause an arteriopathy
      predisposing to CAD in combination with certain trigger and risk factors. The
      clinical spectrum includes local pain in the neck, headaches, Horner's syndrome,
      isolated cranial nerve deficits, and hemispheric or brainstem infarction.
      Noninvasively, CAD is confirmed by Duplex sonography, MRI, and MRA. There is no
      controlled study for best treatment or management. Rational initial empiric
      treatment in acute CAD to prevent secondary embolism is partial thromboplastin
      time-guided anticoagulation by intravenous heparin followed by anticoagulation
      with warfarin. Carotid surgery for treating CAD is not recommended. The duration
      of anticoagulation is best guided by Doppler sonography follow-up and should
      extend until normalization of blood flow or at least 6 months after the vessel
      was occluded. Caution should be recommended for exercises that involve excessive
      head movements. The recurrence rate for CAD is low at <1%/year except for
      patients with known hereditary connective tissue disorders or in cases with
      familial dissections.

PMID- 16897043
TI  - ABCC8 and ABCC9: ABC transporters that regulate K+ channels.
AB  - The sulfonylurea receptors (SURs) ABCC8/SUR1 and ABCC9/SUR2 are members of the C
      branch of the transport adenosine triphosphatase superfamily. Unlike their
      brethren, the SURs have no identified transport function; instead, evolution has
      matched these molecules with K(+) selective pores, either K(IR)6.1/KCNJ8 or
      K(IR)6.2/KCNJ11, to assemble adenosine triphosphate (ATP)-sensitive K(+) channels
      found in endocrine cells, neurons, and both smooth and striated muscle. Adenine
      nucleotides, the major regulators of ATP-sensitive K(+) (K(ATP)) channel
      activity, exert a dual action. Nucleotide binding to the pore reduces the
      activity or channel open probability, whereas Mg-nucleotide binding and/or
      hydrolysis in the nucleotide-binding domains of SUR antagonize this inhibitory
      action to stimulate channel openings. Mutations in either subunit can alter this
      balance and, in the case of the SUR1/KIR6.2 channels found in neurons and insulin
      secreting pancreatic beta cells, are the cause of monogenic forms of
      hyperinsulinemic hypoglycemia and neonatal diabetes. Additionally, the subtle
      dysregulation of K(ATP) channel activity by a K(IR)6.2 polymorphism has been
      suggested as a predisposing factor in type 2 diabetes mellitus. Studies on K(ATP)
      channel null mice are clarifying the roles of these metabolically sensitive
      channels in a variety of tissues.

PMID- 16897049
TI  - [Bilateral cervical arterial dissection as a sign of proximal aortic dissection:
      a rare cause of recidivating TIA].
AB  - Proximal aortic dissection is a life-threatening disease. In addition to other
      complications, involvement of the brain-supplying arteries can lead to acute
      cerebral ischemia. In the presented case, only the patient's clinical course and
      duplex sonography, which showed bilateral cervical arterial dissections, led to
      the diagnosis of aortic dissection. This case emphasizes that early ultrasound
      examination is crucial in patients with suspected cerebral ischemia.

PMID- 16897050
TI  - [Post-stroke depression: clinical aspects, epidemiology, therapy, and
      pathophysiology].
AB  - Post-stroke depression (PSD) is the most frequent psychiatric complication
      following ischemic stroke, affecting up to 50% of all such patients. Moreover,
      PSD is associated with increased morbidity and mortality following ischemic
      stroke. In clinical practice, PSD is underdiagnosed and many affected patients do
      not receive adequate treatment. This review article summarizes current knowledge
      regarding epidemiogy, clinical features, risk factors and predisposition,
      therapy, and prophylaxis of PSD.

PMID- 16897054
TI  - Urinothorax: an unexpected cause of severe dyspnea.

PMID- 16897051
TI  - [Immunology in schizophrenic disorders].
AB  - This manuscript deals with whether immune-mediated mechanisms of inflammation
      contribute to the pathogenesis of schizophrenia. A model is presented which
      integrates psychoneuroimmunologic findings and actual results from
      pharmacological, neurochemical, and genetic studies in schizophrenia. A pivotal
      role in the neurobiology of schizophrenia is played by dopaminergic
      neurotransmission, which is modulated by influences of the glutamatergic system.
      The decreased function of the glutamate system described in schizophrenia seems
      primarily mediated by N-methyl-D-aspartate (NMDA) receptor antagonism. Kynurenine
      acid is the only known endogenous NMDA receptor antagonist. In higher
      concentrations it blocks the NMDA receptor, but in lower concentrations it blocks
      the nicotinergic acetylcholin receptor, which has a prominent role in cognitive
      functions. Therefore, higher levels of kynurenine acid may explain psychotic
      symptoms and cognitive dysfunction. Several findings point out that prenatal
      infection, associated with an early sensitisation of the immune system, may
      result in an imbalance of the immune response (type 1 vs type 2) in
      schizophrenia. This immune constellation leads to inhibition of the enzyme
      indoleamin dioxigenase (IDO). It and tryptophane 2,3-dioxygenase (TDO) both
      catalyse the degradation from tryptophan to kynurenine. Due to the inhibition of
      IDO, tryptophan is metabolised to kynurenine primarily by TDO. In the CNS, TDO is
      located only in astrocytes, which are in particular activated in schizophrenia
      and in which kynurenine acid is the final product and can not be further
      metabolised. Therefore kynurenine acid accumulates in the CNS of schizophrenics
      and - due to its NMDA-antagonistic properties - leads to cognitive dysfunction
      and psychotic symptoms. This model describes the pathway of immune-mediated
      glutamatergic-dopaminergic dysregulation, which may lead to the clinical symptoms
      of schizophrenia. Therapeutic consequences (e.g. cyclo-oxygenase-2 inhibitors)
      are discussed.

PMID- 16897055
TI  - Periaortic lymphoma as a mimic of posttraumatic intramural hematoma.
AB  - Computed tomography (CT) of an 87-year-old man who presented to the emergency
      department with chest pain after a motor vehicle collision demonstrated multiple
      broken ribs and a thoracic periaortic soft tissue mass which was high density on
      precontrast images and enhanced postcontrast. The scan also demonstrated a mass
      encircling the left ureter and masses in the axilla and pelvis. The enhancement
      of the periaortic lesion and the presence of the additional soft tissue masses
      suggested lymphoma as opposed to intramural hematoma (IMH). The diagnosis of
      follicular B-cell lymphoma was rapidly confirmed with fluorodeoxyglucose-positron
      emission tomography/CT and excisional biopsy of the axillary lymph node. While
      this is an atypical presentation, lymphoma and other extravascular pathology must
      be considered in the evaluation of a periaortic high attenuation mass seen on CT.

PMID- 16897058
TI  - Functional genomics: applying calcium imaging and RNA interference to Drosophila
      cell lines to identify new roles for gene products.
AB  - The selective knockdown of genes using RNA interference, and the analysis of the
      resultant phenotype using calcium imaging, is proving to be a powerful
      combination for discovering new genes involved in calcium signalling. This
      technical note describes the application of this approach to the Drosophila S2
      cell line and its derivatives.

PMID- 16897059
TI  - Soil-to-grain transfer of fallout 90Sr for 28 winter wheat cultivars.
AB  - In order to identify wheat cultivars with minimum soil-to-grain transfer of
      fallout 90Sr, 28 winter wheat cultivars were investigated at three different
      sites with different soil types in Upper Bavaria. Each cultivar was grown on an
      area of 10 m2 and harvested in August 1999. Mean soil-to-grain concentration
      ratios (C(r)) were 0.151 +/- 0.029, 0.205 +/- 0.035 and 0.060 +/- 0.012,
      respectively. The C(r) values obtained varied by factors of up to 2.6 for the
      different cultivars at a given site, and by factors of up to 5.0 for the
      different sites and a given cultivar. Site-averaged normalized concentration
      ratios (SANC(r)) ranged from 0.666 +/- 0.062 to 1.503 +/- 0.161. The cultivars
      Convent, Ludwig, and Semper, showed the lowest uptake of (90)Sr compared to the
      mean of all cultivars at each site. A cultivar that shows both minimum uptake of
      90Sr and 137Cs could not be identified. The results suggest that 90Sr rather than
      137Cs might be the limiting radionuclide concerning the use of contaminated land
      for wheat production. Thus, more efforts might be necessary identifying wheat
      cultivars with minimum 90Sr uptake.

PMID- 16897060
TI  - Mathematical simulation of dose-effect relationships for fish eggs exposed
      chronically to ionizing radiation.
AB  - A mathematical model which simulates the observed dose-effect relationships for
      fish eggs exposed to chronic irradiation is presented. The model assumes that the
      exposed fish eggs may exist in one of the following states: normally developing,
      reversibly damaged, and lethally damaged. Reversible damages may be recovered by
      repairing mechanisms which are spent for the repairing processes. The model was
      applied to describe the observed differences in effects of chronic exposure for
      quickly (2 weeks) and slowly (up to 20 weeks) developing fish eggs. Calculations
      were performed for dose rates of chronic irradiation ranging from 10 to 300
      mGy/day. Two types of radiation effects were considered-the effect on eggs
      survival (percentage of survived eggs at time t), and the depletion of the
      repairing pool (in percentage of its maximal value). The model predictions have
      been compared with the experimental data from the EPIC database. This comparison
      showed that the model adequately describes the radiation effects in fish eggs of
      different species, within a wide range of chronic radiation exposures.

PMID- 16897061
TI  - Human biokinetics of strontium--part II: Final data evaluation of intestinal
      absorption and urinary excretion of strontium in human subjects after stable
      tracer administration.
AB  - Fractional intestinal absorption (f1 value) and urinary excretion of strontium in
      healthy human volunteers has been measured by simultaneous oral and intravenous
      administration of the stable isotopes 86Sr and 84Sr using the double-isotope
      method. Final evaluation of the complete data set confirmed that ingestion of
      different foodstuff and nutritional factors could influence the fractional gut
      uptake of strontium. In some cases, significant deviations from the f1 value
      adopted by the International Commission on Radiological Protection (ICRP) were
      found. The arithmetic mean (+/- standard deviation) of the f1 values of all
      experiments performed was determined to be 0.46 (+/- 0.24). The probability
      distribution function of the f1 values is represented by a lognormal curve with a
      geometric mean of 0.38 and a geometric standard deviation of 2.06. Urinary
      excretion in all subjects varied depending on the administered foodstuff in a
      wide range and differs from the ICRP model, up to 2 days after tracer
      administration. No age or gender dependence of the absorbed strontium fraction
      and of the urinary excretion of strontium after an oral load was found.

PMID- 16897063
TI  - Laboratory of attention and brain recovery at Washington University, St. Louis.

PMID- 16897062
TI  - Mortality from cardiovascular diseases in the German uranium miners cohort study,
      1946-1998.
AB  - An increased risk of cardiovascular diseases after exposure to low doses of
      ionizing radiation has been suggested among the atomic bomb survivors. Few and
      inconclusive results on this issue are available from miner studies. A positive
      correlation between coronary heart disease mortality and radon exposure has been
      reported in the Newfoundland fluorspar miners study, yet low statistical power
      due to small sample size was of concern. To get further insight into this
      controversial issue, data from the German uranium miners cohort study were used,
      which is by far the largest miner study up to date. The cohort includes 59,001
      male subjects who were employed for at least six months between 1946 and 1989 at
      the former Wismut uranium company in Eastern Germany. Exposure to radon, long
      lived radionuclides and external gamma radiation was estimated by using a
      detailed job-exposure matrix. About 16,598 cohort members were deceased until 31
      December 1998, including 5,417 deaths from cardiovascular diseases. Linear
      Poisson regression models were used to estimate the excess relative risk (ERR)
      per unit of cumulative radiation exposure after adjusting for attained age and
      calendar period. No trend in risk of circulatory diseases with increasing
      cumulative exposure to either radon [ERR per 100 working level month: 0.0006; 95%
      confidence limit (CI): -0.004 to 0.006], external gamma radiation (ERR per Sv: 
      0.26, 95% CI: -0.6 to 0.05) or long-lived radionuclides (ERR per 100 kBqh/m3: 
      0.2, 95% CI: -0.5 to 0.06), respectively, was observed. This was also true for
      the sub-group heart disease and stroke. Our findings do not support an
      association between cardiovascular disease mortality and exposure to radiation
      among miners, yet low doses and uncontrolled confounding hamper interpretation.

PMID- 16897065
TI  - Music-to-language transfer effect: may melodic ability improve learning of tonal
      languages by native nontonal speakers?
AB  - In tonal languages, as Mandarin Chinese and Thai, word meaning is partially
      determined by lexical tones. Previous studies suggest that lexical tones are
      processed by native listeners as linguistic information and not as pure tonal
      information. This study aims at verifying if, in nontonal languages speakers, the
      discrimination of lexical Mandarin tones varies in function of the melodic
      ability. Forty-six students with no previous experience of Mandarin or any other
      tonal language were presented with two short lists of spoken monosyllabic
      Mandarin words and invited to perform a same-different task trying to identify
      whether the variation were phonological or tonal. Main results show that subjects
      perform significantly better in identifying phonological variations rather than
      tonal ones and interestingly, the group with a high melodic ability (assessed by
      Wing subtest 3) shows a better performance exclusively in detecting tonal
      variations.

PMID- 16897064
TI  - Identification of partially presented meaningless patterns: effect of
      completeness and distinctiveness.
AB  - The role of parts versus that of wholes in a visual perception has been debated
      for a century as two opposite approaches, namely, an analytic and holistic. In
      two psychophysical experiments we investigated whether the stimulus completeness
      or distinctiveness is essential for identification of the partially presented
      patterns under brief presentation conditions. For this purpose, a special class
      of stimuli was constructed in such a way that the patterns could be divided into
      informative and redundant parts. The first experiment clearly demonstrated the
      importance of the redundant part for effective pattern identification for the
      majority of subjects. The second experiment revealed the direct dependence of
      identification accuracy of the patterns on their completeness (2, 3, 4, 5, or 6
      elements). Familiarisation of subjects with the test stimuli influenced the
      strength of this dependence.

PMID- 16897066
TI  - Operational Noology as a new methodology for the study of thought and language:
      theoretical aspects and possible practical applications.
AB  - In this article, the author presents a new methodology for the study of two
      fundamental components of consciousness, that is thought and language. The
      fundamental presupposition that forms the basis of this methodology is that
      thought is not simply a passive "reflection" of an external "reality", but also
      (and especially) something active, i.e. that the fundamental components of
      thought are sequences of operations, amongst which the ones of attention play a
      key role. These sequences of elementary mental operations are called mental
      categories, and are the meanings of all the words that do not seem to indicate
      something physical (first of all, all the "grammatical" words, that is
      conjunctions, prepositions, articles, pronouns, fundamental verbs like "to be",
      "to have" etc., the main adverbs, and, in the large number of languages that have
      a more or less rich morphology, all morphemes (the ones which indicate cases, in
      languages that have cases, the number and the gender of nouns and adjectives,
      moods and tenses of the verb etc.). The author proposes a list of these
      elementary mental operations and he shows how it is possible, basing ourselves on
      them, to identify the meanings of these words, which are indispensable for any
      linguistic expression. The author also mentions a possible short-term practical
      application of these theories, i.e. a device in order to improve the quality of
      machine translation. He also formulates the hypothesis that these theories could
      allow us to look in a new way at the problem of the (partial) artificial
      reproduction of the human activity of thought and language.

PMID- 16897067
TI  - A presentation of attentional semantics.
AB  - The paper presents the two main assumptions of Attentional Semantics--(A) and
      (B), and its main aim (C). (A) Conscious experience is determined by attention:
      there cannot be consciousness without attention. Consciousness is explained as
      the product of attentional activity. Attentional activity can be performed thanks
      to a special kind of energy: nervous energy. This energy is supplied by the organ
      of attention. When we perform attentional activity, we use our nervous energy.
      This activity directly affects the organ of attention, causing a variation in the
      state of the nervous energy. This variation constitutes the phenomenal aspect of
      consciousness. (B) Words are tools to pilot attention. The meanings of words
      isolate, de-contextualize, "freeze" and classify in an articulated system the
      ever-changing and multiform stream of our conscious experiences. Each meaning is
      composed of the sequence of invariable elements that, independently of any
      individual occurrence of a given conscious experience, are responsible for the
      production of any instance of that conscious experience. The elements composing
      the meanings of words are attentional operations: each word conveys the condensed
      instructions on the attentional operations one has to perform if one wants to
      consciously experience what is expressed through and by it. (C) Attentional
      Semantics aims at finding the attentional instruction conveyed by the meanings of
      words. To achieve this goal, it tries: (1) to identify the sequence of the
      elementary conscious experiences that invariably accompany, and are prompted by,
      the use of the word being analyzed; (2) to describe these conscious experiences
      in terms of the attentional operations that are responsible for their production;
      and (3) to identify the unconscious and non-conscious operations that, directly
      or indirectly, serve either as the support that makes it possible for the
      attentional operations to take place, be completed, and occur in a certain way,
      or as the necessary complement that makes it possible to execute and implement
      the activities determined and triggered by the conscious experiences. The origins
      of Attentional Semantics are also presented, and the methodological problems
      researchers encounter when analyzing meanings in attentional terms are discussed.
      Finally, a brief comparison with the other kinds of semantics is made.

PMID- 16897069
TI  - Anatomical study of the femoral and tibial insertions of the anterolateral and
      posteromedial bundles of human posterior cruciate ligament.
AB  - For posterior cruciate ligament (PCL) reconstruction, two root, anterolateral and
      posteromedial bundles restruction are performed. However, little has been
      mentioned of anatomical measurements of the insertions to the bone of these
      bundles in previous publications. The aim of this study is to determine the
      precise anatomical measurements of the femoral and tibial insertions for
      anterolateral and posteromedial bundles of PCL. A total of 32 femur and 33 tibiae
      were selected from 50 cadavers after exclusion of knees that displayed
      macroscopically degenerative changes or evidence of trauma. PCL were divided into
      anterolateral bundles and posteromedial bundles to the insertion footprint, and
      those locations were measured and described. The distance from the center of the
      femoral insertions of the anterolateral and posteromedial bundles, and the
      Wrisberg ligament to the anterior margin of the medial femoral condyle averaged
      9.6, 10.6, and 17.1 mm, respectively. The distance from the center of the femoral
      insertions of the anterolateral, posteromedial bundles, and Wrisberg ligament to
      the intercondylar roof averaged 4.8, 11.4, and 10.4 mm, respectively. The
      distance from the medial margin of the articular cartilage of the tibial plateau
      to the center of the tibial insertions of the anterolateral and posteromedial
      bundles averaged 51.0 and 50.0% of the total widest width of the tibial plateau,
      respectively. The vertical distance from the tibial insertion of the center of
      the posteromedial bundle to the plane of the tibial articular surface averaged
      4.6 mm. This study leads to a better definition of the anatomy of the
      anterolateral and posteromedial bundles of PCL. It is very important to know the
      precise anatomy of PCL bundles when performing PCL reconstruction, and to
      evaluate PCL reconstruction surgery on an anatomical basis.

PMID- 16897068
TI  - Anterior cruciate ligament anatomy and function relating to anatomical
      reconstruction.
AB  - Recently, the interest in surgical techniques that reconstruct the anteromedial
      (AM) and the posterolateral (PL) bundles of the anterior cruciate ligament (ACL)
      has risen. This review focuses on the structural as well as the mechanical
      properties of the ACL and the anatomical details of the femoral origin,
      midsubstance, and tibial insertion of AM and PL bundles of the ACL. The
      terminology of AM and PL bundles is chosen according to the tibial insertion and
      determined by their functional tensioning pattern throughout knee flexion. Close
      to extension the AM is moderately loose and the PL is tight. As the knee is
      flexed, the femoral attachment of the ACL becomes more horizontally oriented,
      causing the AM bundle to tighten and the PM bundle to loosen up. The ACL has been
      described to be restraint to anterior tibial displacement and internal tibial
      rotation. The rotational component might be represented by the PL bundle. The
      femoral origin has an oval shape with the center of the AM close to over-the-top
      position and the center of the PL close to the anterior and inferior cartilage
      margin. Tibial and femoral insertions of the ACL are over 3.5 times larger when
      compared to the midsubstance and tunnel placement is more challenging because of
      the limited size of potential grafts selection of tunnel site placement. For
      reconstruction, both bone-patellar tendon-bone (BPTB) and quadrupled hamstring
      grafts are used. Structural properties of a 10 mm wide BPTB or quadrupled
      hamstring graft have been reported to be comparable with those of the native ACL.

PMID- 16897070
TI  - Simultaneous patellar tendon avulsion fracture from both patella and tibial
      tuberosity: a case report.
AB  - We present a simultaneous patella tendon avulsion fracture from both sides of its
      attachment in an ectopic ossified patellar tendon. Medially two thirds of the
      patellar tendon was detached from the inferior patella, and laterally one third
      of that from anterior tibial tuberosity with the patellar tendon split.
      Osteosynthesis was used to restore the extensor mechanism of the knee. The result
      at 46 months was good, even though there were some remaining ectopic
      ossifications in the patellar tendon.

PMID- 16897071
TI  - Multilobulated popliteal cyst after a failed total knee arthroplasty.
AB  - Popliteal cyst is a rare finding after total knee arthroplasty (TKA), but when
      present, it might indicate a malfunction of the TKA related to generation of wear
      particles, or loosening. We present a case of a multilobulated popliteal cyst
      developing in a patient 8 years after primary TKA. The cyst was associated with a
      mechanical prosthetic loosening. The primary complaint of the patient was pain in
      the posterior region of the knee. A two-stage procedure consisting of cyst
      excision at first, followed after 5 months by a revision TKA was performed.
      Intraoperatively, a darkish, multilobulated cyst with a well-defined thick wall
      filled with fluid containing polyethylene debris, communicating with the knee
      joint was found. After 3 years of follow-up, the patient was satisfied and walked
      without the support of a cane. The patient presented a satisfactory knee range of
      motion. Clinical, radiological and ultrasound investigations ruled out popliteal
      cyst recurrence. A dissecting popliteal cyst associated with a failed TKA should
      be excised because it contains polyethylene debris that constitutes an induced
      factor for prosthetic loosening. A two-stage procedure with quite a long time in
      between, as presented in this paper, can be a useful alternative to manage such a
      problem, in particular in very old patients associated with other medical
      problems.

PMID- 16897072
TI  - Tibial slope and high tibial osteotomy using the circular external fixator.
AB  - Alteration of tibial slope is one of the important anatomical changes of the
      proximal tibia after high tibial osteotomy. Increased or decreased tibial slope
      can effect further total knee prosthesis procedure. In this retrospective study,
      18 knees of 17 patients (17 female, mean age 51 range 43-61, mean BMI is 33.6 +/-
      4.6 kg/m2) who were applied high tibial osteotomy using circular external fixator
      due to medial compartment arthrosis of the knee were evaluated in terms of tibial
      slope changes. While mean correction about 12.3 degrees in mechanical femoro
      tibial angle was obtained in frontal plan (P = 0.0001), significant change in
      tibial slope was not determined in sagittal plan (P = 0.127). The mean posterior
      proximal femoral angle values were measured as 79.5 +/- 2.1 degrees
      preoperatively and as 80.3 +/- 2.7 degrees postoperatively and found to fall into
      the normal range (80.4 +/- 1.6 degrees). As there is no significant alteration in
      tibial slope after high tibial osteotomy performed with the Ilizarov system,
      complications due to alteration in tibial slope will not be experienced in follow
      up or in further total knee prosthesis procedure.

PMID- 16897073
TI  - The serum- and glucocorticoid-induced kinase in DOCA-salt hypertension.

PMID- 16897074
TI  - Short-term activation of peroxysome proliferator-activated receptor beta/delta
      increases fatty acid oxidation but does not restore insulin action in muscle
      cells from type 2 diabetic patients.
AB  - Defective fatty acid oxidation in skeletal muscle is one of the possible causes
      of insulin resistance. Peroxisome proliferator-activated receptor beta activators
      are strong inducers of fatty acid oxidation. The aim of this study was to verify
      whether activation of fatty acid oxidation by PPARbeta agonists in human skeletal
      muscle cells prepared from type 2 diabetic patients could improve the reduced
      responses to insulin that characterized this cell model. GW0742 (10 nM)
      significantly increased fatty acid oxidation and oxidative gene expression in
      myotubes prepared from both healthy subjects and type 2 diabetic patients. In
      cells from control subjects, incubation with the agonist for 48 h affected
      neither insulin-induced rate of glycogen synthesis nor the phosphorylation state
      of protein kinase B (PKB serine 473). Myotubes from type 2 diabetic patients
      displayed marked reduction in the effects of insulin on glycogen synthesis and on
      PKB phosphorylation. However, treatment with PPARbeta agonists did not restore
      these defects. Therefore, these results indicate that induction of fatty acid
      oxidation with PPARbeta activators during short-term exposition is not sufficient
      to correct for insulin resistance in muscle cells from type 2 diabetic patients.
      This suggests that additional studies are needed to better characterize the link
      between fatty acid oxidation and insulin sensitivity in humans.

PMID- 16897075
TI  - Integrin alpha2beta1 deficiency does not affect contact hypersensitivity.
AB  - Collagens in the extracellular matrix are thought to play an important role in
      regulating inflammatory responses by affecting cell adhesion and migration. The
      contact between collagens and cells is established mainly by alpha1beta1,
      alpha2beta1 and alpha11beta1integrin receptors. Here, we analyzed the contact
      hypersensitivity (CHS) reaction in mice that were genetically deficient in the
      collagen receptor alpha2beta1. Integrin alpha2beta1 is widely expressed and has
      been suggested to play an important role in mediating inflammatory responses. CHS
      was induced by applying dinitrofluorobenzene to abdominal skin and challenging
      with the same reagent on ear skin. Macroscopically and histologically, ear
      swelling in alpha2beta1-deficient mice did not differ from that in wild-type
      control mice. Immunohistological detection of infiltrated T lymphocytes,
      neutrophils and mast cells in inflamed ear skin revealed similar numbers in
      controls and integrin alpha2beta1-deficient animals. Our results suggest that the
      adhesive functions of integrin alpha2beta1 are dispensable for the CHS response;
      they may be compensated for by the collagen receptor alpha1beta1 or other
      collagen receptors.

PMID- 16897076
TI  - Hyaluronic acid inhibits the adherence and growth of monolayer keratinocytes but
      does not affect the growth of keratinocyte epithelium.
AB  - Hyaluronic acid (HA) is involved in epidermal biology but evidence for its
      functional significance is sparse. In this study, low-calcium monolayer and high
      calcium epithelium cultures of human keratinocytes were used to study the effect
      of up to four different HA preparations on keratinocyte growth and on the
      adherence of proliferating keratinocytes onto the plastic surface coated with
      different matrix proteins. In suboptimally growing monolayer culture, up to 1,000
      microg/ml rooster comb HA and streptococcus equi HA inhibited keratinocyte
      growth. Instead, all HA preparations tested did not affect the growth and
      migration of keratinocyte epithelium using optimal or suboptimal growth
      conditions. In the cell adherence assays, up to 1,000 microg/ml rooster comb HA
      and streptococcus equi HA inhibited the keratinocyte adherence onto the
      fibronectin- and collagen-coated substratum. In contrast to other HA
      preparations, HA from human umbilical cord did not affect the growth of monolayer
      keratinocytes and it increased markedly the cell adherence onto the collagen
      coated substratum. This increase, however, can be attributed to chonroitin
      sulphate proteoglycan contaminant present in this HA preparation. In conclusion,
      HA can inhibit the growth and adherence of proliferating monolayer keratinocytes,
      but it has no apparent effect on the growth and migration of keratinocyte
      epithelium.

PMID- 16897078
TI  - Non-invasive study of gelatinases in sun-exposed and unexposed healthy human skin
      based on measurements in stratum corneum.
AB  - Gelatinases, which belong to the family of matrix metalloproteinases, degrade
      various components of skin, and may be involved in photoaging, since they are
      upregulated by low-dose UV exposure to the skin. However, their behavior in
      healthy human skin is still unclear. In the present study, gelatinases was
      specifically detected in stratum corneum (SC) of skin from sun-exposed sites,
      including the face, in healthy humans, but not in SC of skin from unexposed
      sites. Following experimental UVB irradiation of the abdomen in volunteers,
      gelatinases were detected in tape-stripped SC from the site for several weeks,
      and subsequently disappeared. The appearance of gelatinase in SC after a lag time
      consistent with SC turnover is considered to reflect upregulation of gelatinase
      expression in keratinocytes in response to UVB-exposure of the skin. A survey of
      gelatinases in facial SC samples collected by tape-stripping from the cheeks of
      100 healthy women revealed that the enzyme was present in 90% of subjects. These
      results, taken together, suggest that gelatinase is constantly upregulated by
      sunlight in the facial epidermis of most women during their daily lives, and may
      be an etiological factor in photoaging, e.g., by promoting wrinkle formation.

PMID- 16897077
TI  - Hair follicle reformation induced by dermal papilla cells from human scalp skin.
AB  - To investigate the possibility of hair follicle reformation induced by dermal
      papilla cells in vivo and in vitro. Dermal papilla cells, dermal sheath cells
      obtained from human scalp skin by enzyme digestion were mixed with collagen to
      form mesenchymal cell-populated collagen gels. Superior and inferior epithelial
      cells and bulb matrical cells were then cultured on these gels by organotypic
      culture to recombine bilayer artificial skins. Dermal papilla cells and outer
      root sheath keratinocytes were mingled together and transplanted under
      subcutaneous tissue of the dorsal skin of nude mice. The results of histologic
      examination was observed with HE stain. These recombinants by organotypic culture
      all reformed bilayer structure like nature skin. Hair follicle-like structure
      reformation was found in dermal sheath cell-populated collagen gel when combined
      with superior or inferior epithelial cells. Dermal papilla cells also induced
      superior and inferior epithelial cells to form hair follicle on nude mice. Low
      passage dermal papilla cells mixed with hair follicle epithelial cells reformed
      many typical hair follicle structures and produced hair fibres after
      transplantation on nude mice. The dermal part of hair follicle, such as dermal
      papilla cells and dermal sheath cells, has the ability to induce hair follicle
      formation by interaction with the epithelial cells of hair follicle.

PMID- 16897079
TI  - Expression of DNMT-1 in patients with atopic dermatitis.
AB  - DNA methylation is known to play an important role in gene transcription and
      alterations of methylation that contribute to the development of certain
      disorders such as cancer, immunodeficiency, and autoimmune diseases. We
      investigated the DNA methylation profiles in patients with atopic dermatitis
      (AD). Messenger RNA (mRNA) levels for DNA methyltransferase-1 (DNMT-1) in
      peripheral blood mononuclear cells (PBMC) were examined using a real-time
      quantitative polymerase chain reaction method. The levels of DNMT-1 mRNA were
      significantly lower in PBMC from the AD patients who had higher serum IgE levels
      compared with normal controls. Our observations suggest that suppression of DNMT
      1 might be related to the pathogenesis of AD, especially in whom serum IgE level
      is high. This is the first report of DNMT-1 expression in AD patients.

PMID- 16897080
TI  - A comparative study of oxidant-antioxidant status in stable and active vitiligo
      patients.
AB  - The pathogenetic mechanisms in vitiligo have not been completely clarified. One
      of the major hypotheses in the pathogenesis of vitiligo is the oxidative stress
      hypothesis. The active or stable phase of vitiligo is defined on the basis of the
      progression or appearance of new lesions in the last 3 months and the absence of
      new lesions or their progression in the last 6 months, respectively. Eighteen
      patients with active vitiligo, 18 patients with stable vitiligo, and 40 controls
      were included in this study. We examined serum levels of malondialdehyde,
      selenium, vitamin E and A, and the erythrocyte activities of glutathione
      peroxidase, superoxide dismutase, and catalase. Our results revealed a
      significantly higher level of serum malondialdehyde, selenium in patients with
      active disease compared with the controls. Significant higher increase in
      erythrocytes superoxide dismutase activities was observed in active vitiligo
      group, erythrocyte glutathione peroxidase activity was decreased significantly in
      active disease, whereas erythrocyte catalase activity and plasma vitamin E and A
      levels were not different in vitiligo patients as compared with controls. Our
      study shows that oxidative stress is involved in the pathophysiology of both
      active and stable vitiligo but increased imbalance of antioxidants was observed
      in the blood of active vitiligo patients.

PMID- 16897081
TI  - Press information : Presentation of the 1st Award for Laser Innovation at the
      Annual Meeting of the German Dermatological Laser Society (DDL) in
      Recklinghausen.

PMID- 16897082
TI  - Mutation breeding of chitosanase-producing strain Bacillus sp. S65 by low-energy
      ion implantation.
AB  - In order to obtain an industrial strain with higher chitosanase yield, the wild
      strain Bacillus sp. S65 cells were mutated by a novel mutagen, nitrogen ion beam,
      with energy of 15 keV and dose ranging from 2.6 x 10(14 )to 5.2 x 10(15)
      ions/cm(2). One mutant, s65F5 with high yield of chitosanase was isolated.
      Results showed that the production of chitosanase of s65F5 was dramatically
      increased from 4.1 U/ml in s65 to 25 U/ml by ion beam implantation, while the
      fermentation time was shortened from 72 to 56 h, both of which greatly increased
      efficiency and reduced the cost of industrial production. Besides, the mutagenic
      effects of low-energy ion beam on survival rate showed characteristic down-up
      down pattern, which was different from the traditional mutagens such as UV and
      gamma-ray and the possible mutation mechanism was discussed.

PMID- 16897083
TI  - Modification of small molecules by using cytochrome P450 expressed in Escherichia
      coli.
AB  - We developed a system for bioconverting diverse compounds using P450s produced in
      Escherichia coli. Vectors for the expressing various P450 cDNAs quickly and
      easily in E. coli were developed by using several restriction enzyme sites. Three
      types of P450 (2C2, 2C29, and 2D22) were produced using these plasmids.
      Substrates were directly added to the incubation medium and metabolized. To
      obtain pure product from the medium, we first tried production of P450 in
      synthetic medium. The amount of another P450 2C43 produced in the synthetic
      medium was similar to the amount produced in Luria broth (LB) medium. Next,
      estradiol, a steroid, was added as a substrate, incubated, and the metabolite was
      extracted and analyzed by high-performance liquid chromatography. The metabolite
      extracted from synthetic medium was purer than that obtained from LB medium.
      Three P450s (2C29, 2C2, and 2A4) metabolized testosterone at different positions.
      P450 2C29 metabolized 7-ethoxycoumarin, androstendione, and
      dehydroepiandrosterone in this medium. P450s produced in the synthetic medium may
      be useful for producing various modified compounds for high-throughput screening.

PMID- 16897084
TI  - The A431E mutation in PSEN1 causing familial Alzheimer's disease originating in
      Jalisco State, Mexico: an additional fifteen families.
AB  - Nine families with autosomal dominant Alzheimer's disease (AD), all of whom had
      the Ala431Glu substitution in the PSEN1 gene and came from Jalisco State in
      Mexico, have been previously reported. As they shared highly polymorphic flanking
      dinucleotide marker alleles, this strongly suggests that this mutation arose from
      a common founder. In the current letter, we expand this observation by describing
      an additional 15 independent families with the Ala431Glu substitution in the
      PSEN1 gene and conclude that this mutation is not an uncommon cause of early
      onset autosomal dominant AD in persons of Mexican origin.

PMID- 16897085
TI  - Genetic interactions of a putative Arabidopsis thaliana ubiquitin-ligase with
      components of the Saccharomyces cerevisiae ubiquitination machinery.
AB  - The feasibility of using the Saccharomyces cerevisiae genetic tools to get
      insights into the function of a plant-specific ubiquitin-ligase was examined.
      ATL2 is a potential ubiquitin-ligase of the RING-H2 type that was originally
      isolated as a conditionally toxic Arabidopsis cDNA when overexpressed in yeast.
      ATL2 is a member of an Arabidopsis family that comprises 80 proteins. After
      testing cDNAs from 25 ATL members for toxicity we found that in addition to ATL2
      only ATL63 was toxic, suggesting specific interactions of each one of these two
      ATLs in yeast. We seek to identify suppressors of the ATL2 toxicity in yeast and
      we found that toxicity was suppressed by knock-out mutations on different
      components of the ubiquitination pathway. Suppression was achieved in four
      deubiquitinating enzyme mutants and in one ubiquitin-conjugating enzyme mutant. A
      model is proposed in which Ubc4 and ATL2 act together to target for degradation
      one or more essential yeast proteins, Doa4/Ubp4, Ubp6 and Ubp14 have a role in
      disassembling ubiquitin chains on the target proteins and Ubp15 protects ATL2
      from auto-ubiquitination. We presuppose that our approach can be further utilized
      to analyze the function of this distinctive class of ubiquitin-ligases in yeast
      as well as in Arabidopsis.

PMID- 16897086
TI  - The host acts as a genetic bottleneck during serial infections: an insect-fungal
      model system.
AB  - The genetic variation of a pathogen population is a pivotal component of pathogen
      evolution, having important implications for emerging diseases, nosocomial
      infections, and laboratory subculturing practices. Furthermore, it is undoubtedly
      altered during infection of a host. We address this issue using an insect-fungal
      model system to examine the influence of serial host passage on the genetic
      variation of a pathogen population. Using amplified fragment length polymorphism,
      a strain of the opportunistic fungus, Aspergillus flavus, showing initially 98%
      genetic similarity, was assessed for changes in genetic diversity during repeated
      passage through Galleria mellonella larvae and compared to that of a parallel
      population serially subcultured on artificial media. In two independent trials,
      the genetic diversity of the population passed through the insect dropped
      significantly, while the genetic variation of the population subcultured on media
      increased or remained unchanged. However, there were no changes in virulence or
      the production of protease or aflatoxin, indicating an apparent lack of
      selection. We suggest that the insect acted as a genetic bottleneck, reducing the
      genetic diversity of the A. flavus population. The ability of a host to produce a
      genetic bottleneck in a pathogen population impacts our understanding of emerging
      diseases, nosocomial infections, and laboratory subculturing practices.

PMID- 16897090
TI  - The epidural "fever": what does an obstetrician need to know?

PMID- 16897089
TI  - Y-STR haplotypes in populations from the Eastern Mediterranean region of Turkey.
AB  - We present the frequency distributions of Y-haplotypes determined by ten Y
      chromosomal STR polymorphisms (i.e., DXYS156-Y, DYS19, DYS385, DYS389 I and II,
      DYS390, DYS391, DYS392, DYS393) in unrelated males from the Eastern Mediterranean
      region of Turkey (104 Turkish and Arabian-speaking Eti Turks from Adana area, 111
      Roma and 110 Turks, Kahramanmara degrees area). The haplotype diversity was 0.974
      in the Eti Turks, 0.979 in the Roma, and 0.989 in the Turks. Two variant alleles
      were characterized by sequencing, i.e., allele 9.2 at DXYS156 and 12.2 at DYS385.
      Some of the haplotypes are particular to one of the three populations; some are
      shared by all three populations. A search against the Y-Haplotype Reference
      Database revealed several matches to samples not only from Turkey and neighboring
      regions (e.g., Syria, Iraq) but also from all over Europe.

PMID- 16897091
TI  - Scaling and organization of electroencephalographic background activity and alpha
      rhythm in healthy young adults.
AB  - The coexistence of the broad-band fluctuation and alpha rhythm of the brain
      dynamics is studied based on the zero-crossing property of the local
      electroencephalographic (EEG) recording in eyes closed and eyes open. A two
      component zero-crossing scenario, consisting of a broad-band fractal and narrow
      band rhythm components, is assumed. Scaling is found in the power law
      distribution p(tau) approximately tau(-nu) of the crossing time interval tau of
      the broad-band fluctuation. In alpha dominant brain state, the alpha rhythm
      interval L also exhibits scaling in the form of power law distribution: p(L)
      approximately L(phi). Our main result is the relationship nu + phi approximately
      3 that characterizes the organization of these two prominent features of the
      brain dynamics. The possible role of self-organized criticality of punctuated
      equilibrium in this organization is discussed.

PMID- 16897088
TI  - The endo-beta-mannanase gene families in Arabidopsis, rice, and poplar.
AB  - Mannans are widespread hemicellulosic polysaccharides in plant cell walls.
      Hydrolysis of the internal beta-1,4-D: -mannopyranosyl linkage in the backbone of
      mannans is catalyzed by endo-beta-mannanase. Plant endo-beta-mannanase has been
      well studied for its function in seed germination. Its involvement in other plant
      biological processes, however, remains poorly characterized or elusive. The
      completed genome sequences of Arabidopsis (Arabidopsis thaliana), rice (Oryza
      sativa), and poplar (Populus trichocarpa) provide an opportunity to conduct
      comparative genomic analysis of endo-beta-mannanase genes in these three species.
      In silico sequence analysis led to the identification of eight, nine and 11 endo
      beta-mannanase genes in the genomes of Arabidopsis, rice, and poplar,
      respectively. Sequence comparisons revealed the conserved amino acids and motifs
      that are critical for the active site of endo-beta-mannanases. Intron/exon
      structure analysis in conjunction with phylogenetic analysis implied that both
      intron gain and intron loss has played roles in the evolution of endo-beta
      mannanase genes. The phylogenetic analysis that included the endo-beta-mannanases
      from plants and other organisms implied that plant endo-beta-mannanases have an
      ancient evolutionary origin. Comprehensive expression analysis of all Arabidopsis
      and rice endo-beta-mannanase genes showed divergent expression patterns of
      individual genes, suggesting that the enzymes encoded by these genes, while
      carrying out the same biochemical reaction, are involved in diverse biological
      processes.

PMID- 16897087
TI  - Mitochondria, hydrogenosomes and mitosomes: products of evolutionary tinkering!

PMID- 16897092
TI  - See globally, spike locally: oscillations in a retinal model encode large visual
      features.
AB  - We show that coherent oscillations among neighboring ganglion cells in a retinal
      model encode global topological properties, such as size, that cannot be deduced
      unambiguously from their local, time-averaged firing rates. Whereas ganglion
      cells may fire similar numbers of spikes in response to both small and large
      spots, only large spots evoke coherent high frequency oscillations, potentially
      allowing downstream neurons to infer global stimulus properties from their local
      afferents. To determine whether such information might be extracted over
      physiologically realistic spatial and temporal scales, we analyzed artificial
      spike trains whose oscillatory correlations were similar to those measured
      experimentally. Oscillatory power in the upper gamma band, extracted on single
      trials from multi-unit spike trains, supported good to excellent size
      discrimination between small and large spots, with performance improving as the
      number of cells and/or duration of the analysis window was increased. By using
      Poisson distributed spikes to normalize the firing rate across stimulus
      conditions, we further found that coincidence detection, or synchrony, yielded
      substantially poorer performance on identical size discrimination tasks. To
      determine whether size encoding depended on contiguity independent of object
      shape, we examined the total oscillatory activity across the entire model retina
      in response to random binary images. As the ON-pixel probability crossed the
      percolation threshold, which marks the sudden emergence of large connected
      clusters, the total gamma-band activity exhibited a sharp transition, a phenomena
      that may be experimentally observable. Finally, a reanalysis of previously
      published oscillatory responses from cat ganglion cells revealed size encoding
      consistent with that predicted by the retinal model.

PMID- 16897093
TI  - Modeling the contribution of lamina 5 neuronal and network dynamics to low
      frequency EEG phenomena.
AB  - The Electroencephalogram (EEG) is an important clinical and research tool in
      neurophysiology. With the advent of recording techniques, new evidence is
      emerging on the neuronal populations and wiring in the neocortex. A main
      challenge is to relate the EEG generation mechanisms to the underlying circuitry
      of the neocortex. In this paper, we look at the principal intrinsic properties of
      neocortical cells in layer 5 and their network behavior in simplified simulation
      models to explain the emergence of several important EEG phenomena such as the
      alpha rhythms, slow-wave sleep oscillations, and a form of cortical seizure. The
      models also predict the ability of layer 5 cells to produce a resonance-like
      neuronal recruitment known as the augmenting response. While previous models
      point to deeper brain structures, such as the thalamus, as the origin of many EEG
      rhythms (spindles), the current model suggests that the cortical circuitry itself
      has intrinsic oscillatory dynamics which could account for a wide variety of EEG
      phenomena.

PMID- 16897094
TI  - Human volunteer study on the influence of exposure duration and dilution of
      dermally applied N-methyl-2-pyrrolidone (NMP) on the urinary elimination of NMP
      metabolites.
AB  - OBJECTIVES: N-Methyl-2-pyrrolidone (NMP) is a versatile solvent used in various
      industrial processes and applications. Apart from its mildly irritating effects
      on the eyes, the mucous membranes and the skin, NMP has revealed prenatal
      toxicity in animal experiments after the oral administration of high doses. The
      dermal absorption of NMP and the urinary elimination of its main metabolites were
      investigated within an experimental exposure study. METHODS: Four male volunteers
      were exposed to liquid NMP under occlusive conditions on the back of one hand
      with varying exposure times and solvent concentrations. Urine was collected
      before, during and after the exposure and analysed for the main NMP metabolites 5
      hydroxy-N-methyl-2-pyrrolidone (5-HNMP) and 2-hydroxy-N-methylsuccinimide (2
      HMSI). RESULTS: The urinary concentration of the metabolites upon exposure to
      undiluted NMP for 2 h increased rapidly with 5-HNMP reaching a maximum at 4-5 h
      and 2-HMSI after 26-29 h. The application of aqueous NMP solutions resulted in a
      delay of the peak time for 5-HNMP of approximately 6 h as compared with the
      undiluted solvent. An average dermal absorption of 5.4+/-1.5 mg NMP cm(-2) h(-1)
      was calculated for a 2 h exposure to undiluted NMP (6.5+/-2.0 mg NMP cm(-2) h(-1)
      for a 30 min exposure). Aqueous dilution of NMP to 50% was followed by a decrease
      of the absorption to 0.9+/-0.5 mg NMP cm(-2) h(-1). NMP metabolite concentrations
      in the range of the detection limits were found only in isolated urine samples
      after exposure to 10% NMP in aqueous dilution. CONCLUSIONS: NMP is rapidly
      absorbed across the skin and the dermal route may contribute significantly to the
      uptake of the solvent. Therefore, a biomonitoring of NMP exposed workers is
      essential for occupational-medical surveillance. Both urinary metabolites reflect
      the internal dose after a dermal absorption of NMP and thus qualify as suitable
      biomarkers for NMP exposure.

PMID- 16897095
TI  - Effects of work related confounders on the association between silica exposure
      and lung cancer: a nested case-control study among Chinese miners and pottery
      workers.
AB  - OBJECTIVE: The role of silica in the causation of lung cancer is an ongoing
      debate. In order to explore whether observed association between silica exposure
      and lung cancer is confounded by exposure to other occupational carcinogens, we
      updated a previously nested case-control study among a cohort of male workers in
      29 Chinese mines and factories on the basis of an extended follow-up. METHODS:
      Five hundred and eleven lung cancer cases and 1,879 matched controls were
      selected. Exposure to respirable silica as well as relevant occupational
      confounders were quantitatively assessed based on historical industrial hygiene
      data. The relationship between exposure to silica and lung cancer was analyzed by
      conditional logistic regression analysis adjusted for exposure to arsenic,
      polycyclic aromatic hydrocarbons (PAHs), radon, and smoking. RESULTS: In a crude
      analysis adjusted for smoking only, a significant trend of increasing risk of
      lung cancer with exposure to silica was found for tin, iron/copper miners, and
      pottery workers. But after adjustment for relevant occupational confounders, no
      relationship between silica and lung cancer can be observed. Instead, there is a
      significant association between lung cancer mortality and cumulative exposure to
      inorganic arsenic (OR = 1.86, 95% CI: 1.14, 3.04 for each mg/m(3)-year increase)
      and carcinogenic PAHs (OR = 1.35, 95% CI: 1.08, 1.69 for each 100 microg/m(3)
      year increase). CONCLUSION: This analysis does not provide any evidence to show
      that exposure to silica causes lung cancer in the absence of confounding factors.

PMID- 16897096
TI  - A 5-year follow-up study on respiratory disorders and lung function in workers
      exposed to organic dust from composting plants.
AB  - OBJECTIVES: To evaluate acute and chronic effects of long-term exposure to
      organic dust on respiratory disorders and lung function among employees at 41
      composting facilities in Germany. METHODS: A total of 218 compost workers and 66
      control subjects were enrolled in the cohort. They were evaluated using a
      standardized questionnaire, a clinical examination, and spirometric measurements.
      Changes of symptoms, respiratory disorders, and lung function were determined in
      a first survey after 5 years of exposure in 123 compost workers and 48 controls.
      Exposure measurements were performed at six composting facilities for respirable
      dust, cultivable microorganisms, and endotoxins. RESULTS: Exposure measurements
      revealed high concentrations of thermo-tolerant/thermophilic actinomycetes and
      filamentous fungi in the bio-aerosols at the composting sites. A significantly
      higher job fluctuation was observed among the compost workers compared to control
      subjects (95 vs. 18; p < 0.05). Compost workers reported a significantly higher
      prevalence of mucosal membrane irritation (MMI) of the eyes and upper airways
      than control subjects. Conjunctivitis was diagnosed significantly more often in
      compost workers. Forced vital capacity in percent of predicted (FVC%) of the non
      smoking compost workers declined significantly (-5.4%) during the observation
      period compared to control subjects. The decline of FVC% in 16 compost workers
      exceeded 10% of initial values. A significant increase was observed in the number
      of compost workers suffering from chronic bronchitis (RR = 1.41; 95% CI = 1.28
      1.55). Allergic alveolitis was diagnosed clinically in two compost workers.
      CONCLUSIONS: The exposure to organic dust at workplaces of composting facilities
      is associated with adverse acute and chronic respiratory health effects,
      including MMI, chronic bronchitis, and an accelerated decline of FVC%. The
      pattern of health effects differs from those at other workplaces with exposures
      to organic dust possibly due to high concentrations of thermo
      tolerant/thermophilic actinomycetes and filamentous fungi at composting plants.

PMID- 16897097
TI  - Individual lifetime exposure to inorganic arsenic using a space-time information
      system.
AB  - OBJECTIVES: A space-time information system (STIS) based method is introduced for
      calculating individual-level estimates of inorganic arsenic exposure over the
      adult life-course. STIS enables visualization and analysis of space-time data,
      overcoming some of the constraints inherent to spatial-only Geographic
      Information System software. The power of this new methodology is demonstrated
      using data from southeastern Michigan where 8% of the population is exposed to
      arsenic >10 microg/l (the World Health Organization guideline) in home drinking
      water. METHODS: Participants (N=440) are members of a control group in a
      population-based bladder cancer case-control study in southeastern Michigan and
      were recruited by phone using random digit dialing. Water samples were collected
      and analyzed for arsenic at current residence and participants were required to
      answer questions concerning lifetime mobility history and dietary habits.
      Inorganic arsenic concentrations were estimated at past residences and
      workplaces, and in select foods. Fluid and food consumption data were integrated
      with mobility histories and arsenic concentrations to calculate continuous
      estimates of inorganic arsenic intake over the adult life-course. RESULTS:
      Estimates of continuous arsenic exposure are displayed, making use of both
      participant age and calendar year as measures of time. Results illustrate
      considerable temporal variability in individual-level exposure, with 26% of the
      participants experiencing a change in drinking water arsenic concentration of at
      least +/-10 microg/l over their adult lives. The average cumulative intake over
      the adult life-course ranges from 2.53 x 10(4)-1.30 x 10(5) microg, depending on
      the selected exposure metric. CONCLUSIONS: The STIS-based exposure assessment
      method allows for flexible inclusion of different parameters or alternative
      formulations of those parameters, thus enabling the calculation of different
      exposure metrics. This flexibility is particularly useful when additional
      exposure routes are considered, input datasets are updated, or when a scientific
      consensus does not exist regarding the proper formulation of the exposure metric.
      These results demonstrate the potential of STIS as a useful tool for calculating
      continuous estimates of adult lifetime exposure to arsenic or other environmental
      contaminants for application in exposure and risk assessment.

PMID- 16897099
TI  - [Systemic sclerosis--a challenge in rheumatology].
AB  - The connective tissue disease systemic sclerosis (SSc) is still a challenge to
      every rheumatologist. SSc is characterized by progressing fibrosis of the skin
      and internal organs, abnormal activation of the immune system and distinct
      changes in microcirculation. Although it is a rare disease with a prevalence of
      about 20:100,000 one may come across it in daily practice. SSc is classified into
      limited and diffuse forms. Both entities usually involve internal organs. Life
      expectancy is limited and depends predominantly on the extent of the organs
      involved. Therefore, it is essential to diagnose SSc early and to identify and
      closely monitor the organs involved.

PMID- 16897098
TI  - Biased competition and visual search: the role of luminance and size contrast.
AB  - The biased-competition theory of attention proposes that objects compete for
      cortical representation in a mutually inhibitory network; competition is biased
      in favor of the attended item. Here we test two predictions derived from the
      biased-competition theory. First we assessed whether increasing an object's
      relative brightness (luminance contrast) biased competition in favor of (i.e.,
      prioritized) the brighter object. Second we assessed whether increasing an
      object's size biased competition in favor of the larger object. In fulfillment of
      these aims we used an attentional capture paradigm to test whether a featural
      singleton (an item unique with respect to a feature such as size or brightness)
      can impact attentional priority even when those features are irrelevant to
      finding the target. The results support the prediction that a singleton with
      respect to luminance contrast receives attentional prioritization and extend the
      biased-competition account to include size contrast, because a large singleton
      also receives attentional prioritization.

PMID- 16897100
TI  - The breakage-fusion-bridge (BFB) cycle as a mechanism for generating genetic
      heterogeneity in osteosarcoma.
AB  - Osteosarcoma (OS) is characterized by chromosomal instability and high copy
      number gene amplification. The breakage-fusion-bridge (BFB) cycle is a well
      established mechanism of genome instability in tumors and in vitro models used to
      study the origins of complex chromosomal rearrangements and cancer genome
      amplification. To determine whether the BFB cycle could be increasing the de novo
      rate of formation of cytogenetic aberrations in OS, the frequency of anaphase
      bridge configurations and dicentric chromosomes in four OS cell lines was
      quantified. An increased level of anaphase bridges and dicentrics was observed in
      all the OS cell lines. There was also a strong association between the
      frequencies of anaphase bridges, dicentrics, centrosomal anomalies, and
      multipolar mitotic figures in all the OS cell lines, indicating a possible link
      in the mechanisms that led to the structural and numerical instabilities observed
      in OS. In summary, this study has provided strong support for the role of the BFB
      cycle in generating the extensive structural chromosome aberrations, as well as
      cell-to-cell cytogenetic variation observed in OS, thus conferring the genetic
      diversity for OS tumor progression.

PMID- 16897101
TI  - [Treatment anxiety in oral and maxillofacial surgery].
AB  - BACKGROUND: Oral and maxillofacial operations are stressful treatment situations
      for patients. Specific data on this phenomenon were acquired through a
      multicenter study. MATERIAL AND METHODS: A 10-page questionnaire was answered by
      600 oral and maxillofacial patients before individual treatment. Control groups
      consisted of 800 surgical, dental, internal medicine and general practitioner
      patients. 26 practices and hospital departments in 11 German cities were involved
      in the study. RESULTS: Both subjective anxiety assessment by patients and
      objective measurement (State Trait Anxiety Inventory; STAI) indicated a high
      level of treatment anxiety for oral and maxillofacial treatment. STAI scores for
      OMFS patients were significantly higher than in control groups. Especially female
      patients, patients treated under local anaesthesia and out-department patients
      showed high anxiety scores. Treatment experience in oral and maxillofacial
      surgery does not modify anxiety in case of recurrent treatment. CONCLUSION:
      Managing perioperative anxiety today is still a major challenge in oral and
      maxillofacial surgery. Irrespective of technical and pharmacological advances
      further studies on this topic and the development and establishing of stress
      reducing and anxiolytic perioperative techniques are of considerable importance.

PMID- 16897102
TI  - Finite element modeling of aponeurotomy: altered intramuscular myofascial force
      transmission yields complex sarcomere length distributions determining acute
      effects.
AB  - Finite element modeling of aponeurotomized rat extensor digitorium longus muscle
      was performed to investigate the acute effects of proximal aponeurotomy. The
      specific goal was to assess the changes in lengths of sarcomeres within
      aponeurotomized muscle and to explain how the intervention leads to alterations
      in muscle length-force characteristics. Major changes in muscle length-active
      force characteristics were shown for the aponeurotomized muscle modeled with (1)
      only a discontinuity in the proximal aponeurosis and (2) with additional
      discontinuities of the muscles' extracellular matrix (i.e., when both
      myotendinous and myofascial force transmission mechanisms are interfered with).
      After muscle lengthening, two cut ends of the aponeurosis were separated by a
      gap. After intervention (1), only active slack length increased (by approximately
      0.9 mm) and limited reductions in muscle active force were found (e.g., muscle
      optimum force decreased by only 1%) After intervention (2) active slack increased
      further (by 1.2 mm) and optimum length as well (by 2.0 mm) shifted and the range
      between these lengths increased. In addition, muscle active force was reduced
      substantially (e.g., muscle optimum force decreased by 21%). The modeled tearing
      of the intramuscular connective tissue divides the muscle into a proximal and a
      distal population of muscle fibers. The altered force transmission was shown to
      lead to major sarcomere length distributions [not encountered in the intact
      muscle and after intervention (1)], with contrasting effects for the two muscle
      fiber populations: (a) Within the distal population (i.e. fibers with no
      myotendinous connection to the muscles' origin), sarcomeres were much shorter
      than within the proximal population (fibers with intact myotendinous junction at
      both ends). (b) Within the distal population, from proximal ends of muscle fibers
      to distal ends, the serial distribution of sarcomere lengths ranged from the
      lowest length to high lengths. In contrast within the proximal population, the
      direction of the distribution was reversed. Such differences in distribution of
      sarcomere lengths between the proximal and distal fiber populations explain the
      shifts in muscle active slack and optimal lengths. Muscle force reduction after
      intervention (2) is explained primarily by the short sarcomeres within the distal
      population. However, fiber stress distributions showed contribution of the
      majority of the sarcomeres to muscle force: myofascial force transmission
      prevents the sarcomeres from shortening to nonphysiological lengths. It is
      concluded that interfering with the intramuscular myofascial force transmission
      due to rupturing of the intramuscular connective tissue leads to a complex
      distribution of sarcomere lengths within the aponeurotomized muscle and this
      determines the acute effects of the intervention on muscle length-force
      characteristics rather than the intervention with the myotendinous force
      transmission after which the intervention was named. These results suggest that
      during surgery, but also postoperatively, major attention should be focused on
      the length and activity of aponeurotomized muscle, as changes in connective
      tissue tear depth will affect the acute effects of the intervention.

PMID- 16897103
TI  - Continuum remodeling revisited : deformation rate driven functional adaptation
      using a hypoelastic constitutive law.
AB  - Recent research effort in bone remodeling has been directed toward describing
      interstitial fluid flow in the lacuno-canalicular system and its potential as a
      cellular stimulus. Regardless of the precise contents of the mechanotransduction
      "black box", it seems clear that the fluid flow on which the remodeling is
      predicated cannot occur under static loading conditions. In an attempt to help
      continuum remodeling simulations catch up with cellular and subcellular research,
      this paper presents a simple, strain rate driven remodeling algorithm for density
      allocation and principal material direction rotations. An explicit finite element
      code was written and deployed on a supercomputer which discretizes the remodeling
      process and uses an objective hypoelastic constitutive law to simulate trabecular
      realignment. Results indicate that a target strain rate for this dynamic approach
      is |D ( I )| = 1.7% per second which seems reasonable when compared to observed
      strain rates. Simulations indicate that a morpho-mechanically realistic three
      dimensional bone can be synthesized by applying a few dynamic loads at the
      envelope of common daily physiological rates, even with no static loading
      component.

PMID- 16897106
TI  - Effect of Er,Cr:YSGG laser irradiation on eruption of rat mandibular incisor
      after disturbance of the enamel organ in the pulp.
AB  - To investigate the efficacy of Er,Cr:YSGG (erbium,chromium:yttrium scandium
      gallium garnet) laser irradiation in root canal preparation and to evaluate its
      effect on eruption of rat incisors after disturbance of the enamel organ in the
      pulp, 20 canals of lower left incisor teeth were prepared by K-files followed by
      Er,Cr:YSGG laser irradiation, and 20 canals of right incisors were subjected to K
      files only (control). At 1 week after irradiation, both sides of incisors erupted
      at the same level from the gingival margin. Histological findings showed that
      laser irradiation produced a slightly larger damage in the pulp than that of
      control. Scanning electron microscope observation revealed that laser-treated
      surface revealed a rough, irregular, and very clean surface; there was almost no
      evidence of debris or smear layer, and dentinal tubules were opened. Adequate
      power of Er,Cr:YSGG laser irradiation is effective in root canal preparation
      without disturbance of the eruption.

PMID- 16897107
TI  - Holmium:YAG laser treatment of ureteral calculi: A 5-year experience.
AB  - The purpose of this study was to provide an account of the 5-year experience we
      have gained using holmium:yttrium-aluminium-garnet (Ho:YAG) lasertripsy in the
      treatment of ureteral stones. One-hundred thirty-seven transurethral
      ureterolithotripsies were performed in 131 patients. A Ho:YAG laser device,
      fibres with diameters of 360 and 550 mum, a video camera as well as semi-rigid
      and flexible ureterorenoscopes were used. Results showed that the direct success
      rates-which meant stone-free ureters on the first post-operative day-in the
      upper, middle and lower ureters were 84.6, 88.7 and 94.8%, respectively. The
      final success rates--which meant stone-free ureters 4 weeks after the operation
      without a second intervention--were 84.6, 96.7 and 96.7%, respectively. The
      pulsatile Ho:YAG laser beam fragmented all kinds of stones easily. No ureteral
      stricture or reflux was identified during the follow-up period. The advantages of
      Ho lasertripsy outweighed its disadvantages. Based on our experience, the Ho:YAG
      laser is one of the most effective and safest energy sources in the treatment of
      ureteral calculi.

PMID- 16897108
TI  - Influence of tubule orientation on cone-shaped texture development in laser
      ablated dentin.
AB  - In the present paper, the influence of tubule orientation on surface texture
      development was studied. Specimens of dentin with a wide range of tubule
      orientations were extracted from caries-free human teeth, processed using KrF
      laser radiation, and analyzed by scanning electron microscopy. When a transverse
      cross section of dentin cut perpendicularly to the tooth axis is processed with
      KrF laser radiation, a cone-like topography develops in the inner dentin where
      tubules are parallel to the laser beam. When laser processing is carried out in
      the outer dentin, because tubules are significantly tilted with respect to the
      laser beam, flat surfaces are achieved. The surface texture after laser
      processing depends effectively on the angle between the tubules and the laser
      beam. The dependency of cone growth on tubule orientation was confirmed using a
      simple differential ablation model.

PMID- 16897109
TI  - Effects of the 1,320-nm Nd:YAG laser on transepidermal water loss, histological
      changes, and collagen remodeling in skin.
AB  - The goal of the study is to investigate the effects of the 1,320-nm Nd:YAG laser
      on skin barrier function and dermal remodeling. Forty-eight female mice were
      irradiated with the 1,320-nm laser four times at an interval of 1 week (350
      micros, 10 mm, single pass 10% overlap). Three doses were used: 18, 22, and 26
      J/cm2. Transepidermal water loss (TEWL) was measured at day 0, 1, 7, 21, 30, and
      60 after treatments. Skin biopsies were taken to observe the changes in dermal
      structures and quantify the increases in the number of fibroblasts and collagen
      content. The dose of 22 J/cm2 induced the lowest ratio of TEWL (0.58+/-0.06, p <
      0.05), highest degree of fibroblast proliferation (45.68+/-5.70, p < 0.05), and
      the most increase in type I collagen fibers (49.8%, p < 0.05) and hydroxyproline
      content (85.7%, p < 0.05). The dose of 26 J/cm2 caused marked inflammatory
      infiltration and the most increase in type III collagen fibers. The increase of
      type I collagen fibers was greater than type III collagen fibers for all three
      doses (p < 0.05). Our results demonstrated that 22 J/cm2 was most effective in
      enhancing skin barrier function and stimulating new collagen synthesis. Dermal
      remodeling after the 1,320-nm laser was mainly through the synthesis and
      deposition of collagen type I. Inflammatory reactions were in favor of the
      formation of type III collagen.

PMID- 16897111
TI  - Monitoring of bactericidal action of laser by in vivo imaging of bioluminescent
      E. coli in a cutaneous wound infection.
AB  - The worldwide rise in antibiotic resistance necessitates the development of novel
      antimicrobial strategies. This study aimed to evaluate the bactericidal action of
      an 810-nm diode laser in a cutaneous wound infection. An Escherichia coli strain
      was transformed with a shuttle vector (pRB474) containing firefly luciferase gene
      from Photinus pyralis resulting in a bioluminescent phenotype. Because firefly
      luciferase is an enzyme and as such is prone to inactivation at elevated
      temperature, the first phase has consisted in evaluating in vitro the effect of
      temperature elevation (30, 40, 50, and 60 degrees C for 2 min) on bacteria
      bioluminescence. The second phase was performed in vivo. Two full-thickness
      circular, 14-mm diameter wounds (control and laser-irradiated) were induced on
      rats. Wound infection was carried out using a suspension (50 microl PBS)
      containing 5 x 10(7) cells of bioluminescent E. coli (10(9) cells/ml). Thirty
      minutes later, light irradiation was performed with an 810-nm diode laser (P = 10
      W, psi = 1.4 cm, fluence: 130, 195, and 260 J/cm2). Temperature was measured
      within each wound with a noncontact infrared thermometer. Light emission of the
      bioluminescent bacteria was monitored in vivo by a bioluminescence imaging system
      before and at 4, 8, 24, and 48 h after laser irradiation. In vitro, bacteria
      bioluminescence is not affected when temperature is maintained at 50 degrees C
      for 2 min. In vivo, bioluminescence imaging showed that at 4 h, the viability of
      E. coli was reduced when compared to the control (CTRL) group (p < 0.01). This
      observation was confirmed at 8 h (p < 0.001), at 24 h (p < 0.001), and finally at
      48 h (p < 0.001). Loss of viability of E. coli depends on laser fluence. At 48 h,
      bioluminescent bacteria were not detected (100% loss of viability) in the wound
      irradiated at 260 J/cm2. For this fluence, the temperature reached 45 degrees C
      at the end of the irradiation. This study confirms previous observations on the
      bactericidal effect of diode lasers. Because a progressive desiccation of the
      superficial dermis is usually observed when using laser irradiation, the
      hypothesis that laser irradiation dries out the wound making the wound an
      inhospitable place for bacteria is much more relevant than a direct effect of
      infrared light on chromophores inside bacteria. This is confirmed by the fact
      that in this latter case, one would expect an immediate drop in luminescence
      followed by an increase as the surviving bacteria started to divide and
      repopulate the wound. However, the exact mechanism deserves further studies. This
      study points out the advantage of using bioluminescence imaging to evaluate laser
      for the treatment of acute infections in vivo, nondestructively, and
      noninvasively.

PMID- 16897110
TI  - Laser therapy and surgical treatment in transfusion-dependent patients with upper
      gastrointestinal vascular ectasia.
AB  - We report the results of endoscopic laser therapy on 59 patients with upper
      gastrointestinal vascular ectasia. After 300 sessions, complications were two
      nonbleeding and three bleeding ulcers, treated successfully with endoscopic
      therapy. After treatment, blood transfusions were abolished in 61% and reduced in
      22% of the patients, whereas 17% of the patients were nonresponders and 5% died
      for bleeding. Treatment outcome correlated with endoscopic healing, number of
      yearly transfusions, and lesions' localization. Patients, who did not respond to
      laser therapy by the sixth session, showed no improvement afterwards. Four
      patients with persistence of bleeding despite laser therapy underwent surgery and
      in three of them, a long-term control of bleeding was obtained. In conclusion,
      laser therapy was safe and effective; nonetheless, surgical treatment should be
      considered, after adequate staging, for those patients receiving more than 10
      blood units per year or who have undergone more than six laser sessions without
      improvement.

PMID- 16897113
TI  - LPS-stimulated production of TNF-alpha by peripheral blood monocytes in patients
      with Behcet's disease.
AB  - Tumor necrosis factor alpha (TNF-alpha) is believed to play a significant role in
      disease pathogenesis of Behcet's disease (BD). High serum levels of TNF-alpha
      were repeatedly reported in patients with active BD and anti-TNF agents are
      effective in its treatment. The pathophysiology of TNF-alpha in BD is still
      unknown and conflicting results regarding TNF-alpha overproduction by peripheral
      blood monocytes (PBM) from patients with BD were reported. The aim of the study
      is to compare stimulated production of TNF-alpha by PBM of BD patients with that
      of healthy volunteers (HV) and to examine correlations between the ability of PBM
      to produce TNF-alpha and organ/system involvement in patients with BD. Eighteen
      patients with BD (mean age 38.4+/-12.4 years, 12 males) gave informed consent and
      completed the European BD Current Activity Form. The PBM were separated and
      treated with lipopolysaccharide (LPS) overnight. TNF-alpha levels in the
      supernatants were assayed by ELISA and values were expressed in terms of cell
      protein contents. The control group included 15 HV (mean age 34.2+/-9.9 years,
      seven males). The mean production of TNF-alpha/cell protein (ng/mg) and in-group
      dispersion were similar in both groups (p=0.98). In the subgroup analysis, TNF
      alpha production by PBM in BD patients who reported "bad" or "very bad" global
      well-being over the last month (n=4) was higher compared to other patients with
      better self-rating (p=0.03). PBM of BD patients in the present study did not
      overproduce TNF-alpha upon stimulation with LPS. However, BD patients with a
      higher TNF-alpha-producing capacity had worse sense of well-being.

PMID- 16897112
TI  - Effects of Stanger bath therapy on fibromyalgia.
AB  - The purpose of this study was to assess the effectiveness of Stanger bath on the
      treatment of fibromyalgia (FM). Fifty women with FM were randomly divided into
      two groups. The first group (n=25) was treated with amitriptyline, 10 mg/day for
      8 weeks, and Stanger bath, 20 min daily for ten sessions. The second group (n=25)
      only had amitriptyline, 10 mg/day for 8 weeks. In the first group the assessment
      parameters were measured before (t1), at the end (t2), and 2 months after the
      hydrotherapy (t3). In the second group these parameters were examined before (T1)
      and 2 months after the treatment (T2). Patients were evaluated by number of
      tender points and Fibromyalgia Impact Questionnaire (FIQ) scores. There was
      significant improvement in number of tender points between t1 and t2 (P<0.01) and
      t1 and t3 (P<0.001) in the Stanger bath group. In addition, there was significant
      improvement in FIQ scores between t1 and t2 (P<0.001) and t1 and t3 (P<0.01) in
      the Stanger bath group. In the second group we observed significant improvement
      in FIQ scores and tender point numbers between T1 and T2 (P=0.00). We did not
      find any difference between groups in tender point number percent change
      (p=0.074). However, we observed statistically significant improvement in percent
      change of FIQ scores in Stanger bath group (-30+/-16.7) when compared to group 2
      (-19.3+/-13) (p=0.016). We conclude that Stanger bath therapy when combined with
      amitriptyline has a long lasting effect and better outcome in FM patients.

PMID- 16897114
TI  - The changes in monosaccharide composition of immunoglobulin G in the course of
      rheumatoid arthritis.
AB  - The objective of this study was to determine whether galactosylation of
      immunoglobulin G (IgG) in patients with rheumatoid arthritis (RA) correlates with
      severity and duration of illness. Serum IgG glycosylation from 50 patients with
      RA in comparison with 30 healthy controls was analyzed. IgG from sera was
      isolated and monosaccharide composition was determined by means of gas
      chromatography. Ratio of galactose to mannose content was calculated. Patients
      were divided into groups according to three different criteria: disease duration,
      severity of RA (disease activity score index), and radiological degree of
      advancement of illness according to Steinbrocker. In patients with RA,
      significant decrease (p<0,01) of galactose ratio was observed in comparison with
      healthy control. In patients with long duration of RA (more than 15 years),
      significant decrease of galactose (p<0.05) ratio in comparison with patients who
      have had arthritis for less then 5 years was observed. For the group of patients
      with severe RA, we found reduction of galactose (p<0.001) ratio vs the group of
      patients in remission. For those patients who had radiological stage IV according
      to Steinbrocker, IgG galactose (p<0.01) content per oligosaccharide chain were
      also more decreased than in those patients who had stage I RA. Decreased
      galactosylation and of IgG in RA was observed. The lack of this carbohydrate
      component of IgG correlates with severity and duration of RA and could be used in
      monitoring the progression in early arthritis.

PMID- 16897115
TI  - QT dispersion increases in patients with systemic lupus erythematosus.
AB  - Although autopsy studies have documented that heart is affected in most of
      systemic lupus erythematosus (SLE) patients, clinical manifestations occur in
      less than 10%. QT dispersion, a new parameter that can be used to assess
      homogeneity of cardiac repolarization and autonomic function, has not been
      studied in SLE patients. The aim of our study was to evaluate the QT dispersion
      (QTd) in SLE patients without overt cardiac involvement. Eighty-three patients
      with a diagnosis of SLE (mean age 41+/-13) and age- and sex-matched 77 healthy
      control subjects (mean age 43+/-10) were enrolled in the study. All subjects had
      their complete history taken, laboratory examination, and transthoracic
      echocardiography (ECG). Patients with cardiac disease, hypertension, diabetes, or
      taking medications that may effect QTd or any ECG abnormalities were excluded.
      Resting 12-lead ECG were recorded for measurement of QTd. None of the patients
      and control subjects had overt cardiac involvement. The mean SLE duration was
      86.5+/-15.4 months. QT dispersion was significantly greater in SLE patients than
      incontrol subjects (55.2+/-24.7 vs 20.7+/-5.3 ms, respectively; p<0.001). There
      was no correlation between QTd and duration of SLE, SLEDAI-K score,
      corticosteroid usage, and presence of anti SS-A antibody. QT dispersion is
      significantly increased in SLE patients without overt cardiac involvement. Our
      result suggests that prolonged QT dispersion can be a useful noninvasive and
      simple method for early detection of cardiac involvement in SLE patients.

PMID- 16897116
TI  - Nephropathy, polyneuropathy, and gastroenteritis in a child with Churg-Strauss
      syndrome.
AB  - Churg-Strauss syndrome (CSS) is a serious but rare pauci-immune vasculitis of
      small- and medium-sized blood vessels. It is commonly seen in association with
      bronchial asthma and/or allergic disorders. The syndrome is characterized by the
      presence of asthma, hypereosinophilia, and vasculitis in any part of the body.
      Vasculitis is often associated with significant distortion of normal functions. A
      rather severe case of CSS in an 8-year-old Nigerian girl with asthma and allergic
      rhinoconjunctivitis is reported. She presented with multiple morbidities, namely,
      vasculitic polyneuropathy and also nephritic-nephrotic syndrome that eventuated
      in acute renal failure after an onset of vasculitic gastroenteritis. Routine
      screening of all asthmatic patients for CSS is advocated.

PMID- 16897117
TI  - Magnetic resonance imaging in Lofgren's syndrome: demonstration of periarthritis.
AB  - In Lofgren's syndrome, pain and swelling commonly involves the ankle joints. In
      this prospective case series, the magnetic resonance imaging findings of ankle
      joint involvement are described. Extensive subcutaneous and soft tissue oedema
      was commonly seen around the ankles. Bone, cartilage, ligaments and tendons were
      typically uninvolved. Small amounts of joint and tenosynovial fluid were present
      without evidence of synovial thickening or synovitis. The fluid is probably
      reactive to adjacent inflammation in the para-articular soft tissues and probably
      not representing a primary site of involvement. These findings demonstrate that
      the arthritis in Lofgren's syndrome stems primarily from periarthritis. This is
      consistent with prior descriptions using ultrasonography.

PMID- 16897118
TI  - The evaluation of quality of life in fibromyalgia syndrome: a comparison with
      rheumatoid arthritis by using SF-36 Health Survey.
AB  - Musculoskeletal disorders are the most common causes of deterioration in quality
      of life (QOL). We in this study aimed to assess (1) the impact of fibromyalgia
      syndrome (FS) on QOL comparing with that of rheumatoid arthritis (RA) patients
      and control subjects and (2) the impact of these two musculoskeletal disorders on
      various components of QOL using SF-36 Health Survey. Thirty-five patients with
      RA, 30 patients with FS, and 30 voluntary control subjects were included in the
      study. The groups were comparable in terms of demographic characteristics. QOL
      was evaluated by using Short-Form (SF)-36 Health Survey in all study
      participants, and Fibromyalgia Impact Questionnaire (FIQ), which is a specific
      health-status instrument for FS, was used in FS patients. Physical functioning,
      physical role, social functioning, bodily pain, general health, vitality,
      emotional role, and mental health scores were significantly lower in RA and FS
      patients than in control subjects (p<0.05). The between-groups comparisons
      revealed that FS patients had significantly lower mental health scores than RA
      patients (49.87 vs 62.51, respectively), (p<0.001). Total FIQ score correlated
      significantly with physical functioning, physical role, and bodily pain in FS
      patients. All parameters of SF-36 Health Survey except for social functioning
      correlated significantly with some of the variables of FIQ. FS has a negative
      impact on QOL, like RA. Furthermore, mental health was more severely affected in
      FS patients when compared with RA patients.

PMID- 16897119
TI  - Effects of quadriceps electrical stimulation program on clinical parameters in
      the patients with knee osteoarthritis.
AB  - The aim of this study was to evaluate the effects of electrical stimulation
      program on pain, disability, and quadriceps strength in the patients with knee
      osteoarthritis. Fifty women diagnosed as knee osteoarthritis were randomized into
      two groups as electrical stimulation and biofeedback-assisted isometric
      exercises. Both of the programs were performed 5 days a week, for a duration of 4
      weeks. Outcome measures for pain were visual analogue scale pain score and
      Western Ontario McMaster osteoarthritis index (WOMAC) pain score. Disability and
      stiffness were assessed with WOMAC physical function and stiffness score. One
      repetition maximum (RM) and 10 RM were used for measuring quadriceps strength. In
      addition, 50 m walking time and 10 steps stairs climbing up-down time were
      evaluated. Both groups showed significant improvements in pain, physical
      function, and stiffness scores after the therapy. There were statistically
      significant improvements in 50 m walking time and 10 steps stairs climbing up
      down time and 1 RM and 10 RM values indicating the improvement in muscle
      strength. In addition, there were no significant differences between the groups
      after the therapy. We conclude that electrical stimulation treatment was as
      effective as exercise in knee osteoarthritis and electrical stimulation treatment
      can be suggested especially for the patients who have difficulty in or
      contraindications to perform an exercise program.

PMID- 16897121
TI  - The effect of gabapentin in earlier stage of reflex sympathetic dystrophy.
AB  - The objective of this paper is to investigate the effect of gabapentin in the
      earlier stage of reflex sympathetic dystrophy syndrome (RSD). Twenty-two patients
      diagnosed with RSD were enrolled. Initial gabapentin dosage was 600 mg/day. This
      dosage is increased gradually until a satisfactory pain level was reached. After
      this level, this dosage was maintained throughout the study. An exercise program
      was also applied to the patients. Provoked and static pain scores of the patients
      were obtained initially, at 3-day intervals for maintenance dosage determining,
      and at 6 weeks after the discharge. Functional improvement parameters were
      volumetric measurement; dynamometric measurement and third finger pulp-distal
      palmar crease distance measurement for hands; and metric circumferential
      measurement and range of motion for elbow, knee, and foot initially, at baseline,
      on the tenth day, upon discharge, and 6 weeks after the discharge. The mean
      maintenance dose of gabapentin was 1,145.46+/-377.6 mg/day (range, 900-1,800
      mg/day). Improvements in spontaneous and provoked pain intensities were
      statistically significant. No statistically significant difference was obtained
      in functional improvement parameters. Dizziness in three patients, headache in
      two patients, and mild burning feeling in the tongue in one patient were the
      reported side effects. These symptoms resolved spontaneously in few days.
      Gabapentin cannot be recommended as the drug of choice, but it may be considered
      as one of the therapeutic alternatives in the management of pain due to RSD. We
      suggest that it is effective only for the pain and not for other symptoms of RSD.
      Serious side effects that will cause the patient to stop using the drug are rare.

PMID- 16897120
TI  - Lymphocytic interstitial pneumonitis (LIP) in Sjogren's syndrome: a case report
      and a review of the literature.
AB  - Sjogren's disease is one of the most common rheumatological diseases and can
      present with a variety of extra-glandular manifestations. Lymphocytic
      Interstitial Pneumonitis (LIP) is the most common lung pathology in these
      patients. It is important to know and recognize this condition because it is
      potentially treatable. It is also frequently misdiagnosed and treated as
      infectious pneumonia multiple times before the correct diagnosis is made. It is a
      benign lymphoproliferative disorder characterized histologically by interstitial
      infiltration with polyclonal lymphocytes and plasma cells. High-resolution CT
      scan of the lungs shows extensive areas of ground-glass attenuation and
      interlobular septal thickening with scattered thin-walled cysts. An open-lung
      biopsy is the best method of diagnosing this condition, as less invasive
      techniques do not provide an adequate tissue specimen. LIP occurs in a wide
      variety of settings such as autoimmune disease, HIV disease, and as an adverse
      reaction to some medications; it is, therefore, considered to be a nonspecific
      response to many stimuli. The treatment usually consists of corticosteroids and
      other immunosuppressants, though there have been no controlled trials to date.
      Establishment of a registry may help better evaluate and treat this disease. We
      present the case of a patient who was diagnosed with LIP secondary to Sjogren's
      syndrome and also review the literature available.

PMID- 16897122
TI  - Prevalence and clinical aspects of Behcet's disease in the north of Israel.
AB  - Behcet's disease (BD) has a higher prevalence in countries along the ancient silk
      route, but the actual prevalence in Israel is unknown. We evaluated the
      occurrence and clinical expression of BD in the northern region of Israel: in the
      whole population and by ethnic groups. The sample included all adult patients
      with BD (International Study Group criteria) treated at three medical centers in
      northern Israel. Patient data were collected by file review and physician survey.
      Relevant demographic data for the population served by the medical centers were
      obtained from the official Israeli authorities. A total of 112 patients were
      identified. The overall prevalence of BD was 15.2/100,000 and was similar in men
      and women. The prevalence rates among the Jewish, Arab, and Druze populations
      were 8.6, 26.2, and 146.4 per 100,000, respectively. Age at disease onset was
      similar in all ethnic groups and significantly lower in males (28.6+/-9.7 vs
      32.9+/-11.3, p=0.03). There were no differences in disease manifestations by sex
      or ethnicity. All Druze patients were HLA-B5 positive, compared to 80.8% of the
      Arab patients and 72.0% of the Jewish patients. Recurrent oral ulcers in family
      members were more common in Arab patients (p=0.004). The BD severity index was
      significantly lower in Druze patients (p=0.05), mainly in males (p=0.03). This
      study confirms the high prevalence of BD in Israel and the variability in disease
      rates and expression by ethnic origin. Our findings, particularly regarding the
      Druze population, call for further field surveys and genetic studies.

PMID- 16897123
TI  - Lifelong learning and the reconstructive pelvic surgeon.
AB  - Many challenges face practicing surgeons in today's medical environment.
      Decreasing revenues create a need for increasing patient volume. Increasing costs
      of malpractice insurance not only provide financial burdens, but also cause many
      practitioners to relocate or change the focus of their practice. Technological
      advancements with the rapid emergence of new procedures and medical devices tax
      the practicing physician's ability to keep apace of changes. These changes, in
      combination with increased focus on patient safety and physician competence,
      place even greater demands on practicing in the surgical subspecialties. In this
      environment, finding time to improve skills and gain competence in new procedures
      is a daunting task. This article addresses the topic of surgical competence,
      provides insight into how to learn to do and prove competence to perform new
      surgical procedures, as well as reviews the opportunities available for self
      evaluation currently available for the practicing surgeon.

PMID- 16897124
TI  - Pregnancy in an untreated case of transverse vaginal septum with vesicovaginal
      fistula.
AB  - An 18-year-old woman presented with history of cyclic hematuria, abdominal pain,
      and a mass in the hypogastrium. She was found to have transverse vaginal septum
      in the lower one-third of her vagina with congenital vesicovaginal fistula (VVF)
      and a dead fetus of approximately 20 weeks gestation. She underwent vaginotomy
      and removal of the dead fetus. Vaginal repair of VVF was carried out 3 months
      later.

PMID- 16897125
TI  - Retropubic and transobturator tape procedures: reply to letter by A.C. Wang.

PMID- 16897126
TI  - Incidence and remission of urinary incontinence after hysterectomy--a 3-year
      follow-up study.
AB  - The aim of the study is to investigate the changes in continence status in a
      population of women hysterectomized in 1998-2000. Four hundred fifteen
      hysterectomized women who participated in a questionnaire study on continence
      status in September 2001 were retested with the same questionnaire on actual
      continence status in January 2005. As controls we used 97 women who had a
      laparoscopic cholecystectomy in 1999-2000 and were tested and retested similarly.
      Urinary incontinence was defined as involuntary urinary leakage at least once a
      week. Stress incontinence was defined as leakage when coughing, laughing, or
      lifting heavy weights. Urge incontinence was defined as an uncontrollable desire
      to void with leakage before reaching the toilet. Stress incontinence was reported
      by 30% of the hysterectomized women in 2005 vs 28% in 2001. The similar
      prevalences of urge incontinence were 15 and 13%, respectively. Women who had a
      subtotal hysterectomy significantly more often had stress incontinence compared
      to controls in 2005 and 2001. No other significant differences were found.
      However, the similar prevalences of incontinence reflected that 16% of the
      hysterectomized women changed from continent in 2001 to stress incontinent in
      2005, while 32% changed from stress incontinent to continent. For urge
      incontinence the similar changes were 8 and 35%, respectively. A large proportion
      of women change from continent to incontinent or from incontinent to continent
      during the 3 years of investigation, which should be born in mind when prevalence
      studies on urinary incontinence are evaluated. Previous hysterectomy does not
      seem to be of great importance for the development of de novo incontinence or
      remission.

PMID- 16897127
TI  - Laparoscopic partial cystectomy for a vesical leiomyoma.
AB  - A 47-year-old woman presented with gross hematuria and urinary frequency for 6
      months. The tumor located at the dome of bladder was resected by transurethral
      resectoscope. The pathology revealed leiomyoma; however, her symptoms did not
      improve after the endoscopic procedure. We performed transurethral mucosal
      incision for circumscribing the margin of tumor and transperitoneoscopic partial
      cystectomy to treat the patient successfully.

PMID- 16897128
TI  - Weak VLPP and MUCP correlation and their relationship with objective and
      subjective measures of severity of urinary incontinence.
AB  - The aims of the present study were to find the correlation between Valsalva leak
      point pressure (VLPP) and cough leak-point pressure (CLPP) and to determine
      whether the water perfusion maximum urethral closure pressure (MUCP) correlates
      with VLPP. Seventy-nine women with previously untreated stress urinary
      incontinence were recruited to participate in a clinical study. Their mean age
      was 56.4 years, mean BMI was 27.8, and mean parity was 1.9. The mean values of
      VLPP and CLPP were 50.4 and 52.9 cm H(2)O, respectively. We did not find
      statistically significant differences in the mean values of VLPP and CLPP. The
      mean value of MUCP at rest was 44.2 cm H(2)O and the mean value of MUCP during
      maximal Valsalva maneuver was 37.2 cm H(2)O; with 500 ml of sterile saline in the
      bladder the difference between them is statistically significant. In the study
      group (n=79), 56 patients (77%) had low VLPP (< or =60 cm H(2)O), 21 patients
      (30%) had low MUCP (< or =30 cm H(2)O), and 8 patients had MUCP< or =20 cm H(2)O
      (all at rest). Of the 56 patients with low VLPP, 16 also had a low MUCP (< or =30
      cm H(2)O). This study mainly compares two parameters-the MUCP and the VLPP. Based
      on our results we can conclude that there is no correlation between these
      parameters. MUCP measures urethral resistance at rest and VLPP measures urethral
      resistance during increased intra-abdominal pressure (Valsalva maneuver).

PMID- 16897139
TI  - Symptomatic atrial fibrillation as the first symptom of a giant left atrial
      appendage aneurysm.

PMID- 16897140
TI  - Six-months patency of three long drug eluting stents documented by surveillance
      coronary multi-detector computed tomography (MDCT).

PMID- 16897141
TI  - Coronary-like revascularization for atherosclerotic renal artery stenosis-
      results in 181 consecutive patients.
AB  - AIMS: The aim of this study was to document the early outcome of coronary-like
      revascularization for atherosclerotic renal artery stenosis (ARAS). METHODS AND
      RESULTS: A total of 181 consecutive patient, 102 men, mean age 66.1 (+/- 9.2)
      years and 79 females, mean age 68.4 (+/- 9.2) years and 198 lesions were treated
      between February 1999 and May 2004 for ARAS and retrospectively analyzed. At
      least one major cardiovascular risk factor was present in 179 (98.9%) patients.
      Pre-dilatation ARAS was 81.3+/-9.6%, 27 ARAS were 50-70% and no ARAS was <50%.
      135 (68.2%) of the ARAS lesions were ostial and 63 (31.8%) were non-ostial. In 17
      (9.4%) patients bilateral ARAS were present. Technical success defined as
      residual stenosis < or =30% was achieved in 178 (98.3%) of patients and 195
      (98.5%) of lesions. In one patient (0.5%) the target ARAS could not be crossed,
      in two (1.1%) patients residual stenosis was >30%. No major adverse cardiac or
      cerebral effects were observed. In 3.9% of patients minor local complications of
      the access site occurred; 4 (2.2%) inguinal hematoma, 3 (1.7%) pseudoaneurysm
      were documented. Serum creatinine concentrations and systolic and diastolic blood
      pressure before and after the intervention were not statistically different.
      CONCLUSIONS: Coronary-like approach to ARAS revascularization is technically
      feasible and associated with a very low complication rate.

PMID- 16897142
TI  - Echinococcus cyst located in the interventricular septum.

PMID- 16897144
TI  - Study of the effectiveness of musical stimulation during intracardiac
      catheterization.
AB  - BACKGROUND: Intracardiac catheterization is a routine physical examination. Due
      to psychological strains, several psychosocial interventions, including music
      therapy, have been proposed. The aim of the present study was to examine whether
      the preventive or adjuvant use of music therapy results in a reduction in both
      subjective and objective anxiety and thus leads to a reduction in sedative
      medication. METHODS OF ASSESSMENT: N=83 patients (48 male, 35 female, 66+/-11
      yrs) waiting for scheduled cardiac catheterization were randomly allocated to one
      of three groups: control group (standard care), exposure group (music stimulation
      during the procedure), or coaching group (additional music therapeutic coaching).
      Target variables were subjective anxiety and physiological parameters. RESULTS:
      Music intervention did effectively reduce subjective anxiety (STAI-S reduction
      pre-post: exposure 11 pt, coaching: 4 pt, control: 6 pt; p=0.033). Physiological
      values and medication did not differ between groups. CONCLUSION: The use of music
      stimulation during the catheterization has a relaxing and calming effect on
      patients. It seems to be especially beneficial in a subgroup of patients with
      higher-than-average psychological strains.

PMID- 16897145
TI  - Clinical implication of adenosine-stress cardiac magnetic resonance imaging as
      potential gatekeeper prior to invasive examination in patients with AHA/ACC class
      II indication for coronary angiography.
AB  - BACKGROUND: Real world cardiology is faced with a low diagnostic yield of
      coronary angiography (CXA) in patients presenting with ACC/AHA class II CXA
      indication. Our aim was to analyze the clinical implication of a Cardiac MR (CMR)
      protocol including adenosine stress perfusion in this patient population. We
      examined whether CMR could enhance appropriate CXA indication and thus reduce the
      rate of pure diagnostic CXA. In addition, we compared the relative impact of CMR
      exam components (perfusion, function and viability assessment) in achieving this
      target. METHODS: 176 patients were referred for CXA with class II indication. 171
      underwent complete additional CMR exam in a 1.5-T whole body CMR-scanner for
      myocardial function, ischemia and viability prior to CXA. The routine protocol
      for assessment of CAD consisted of functional imaging (long and short axes),
      adenosine stress- and rest-perfusion in short axis orientation and "late
      enhancement" imaging in long and short axes. Images were analyzed by two
      independent and blinded investigators. Interobserver differences were resolved by
      a third reader. RESULTS: There was a high association between CMR results and
      subsequent invasive findings (chi square for CMR perfusion deficit and stenosis
      >70% in CXA: 113.7, p<0.0001). 109 (63.7%) of our patients had relevant perfusion
      deficits as seen by CMR and matching coronary artery stenosis >70%. Four (2.3%)
      patients had false negative CMR findings. In 58 patients (33.9%) no relevant
      coronary artery stenosis could be observed, correctly predicted by CMR in 48
      cases; in 10 (5.8%) patients CMR provided false positive results. Sensitivity of
      CMR to detect relevant CAD (>70% luminal narrowing) was 0.96, specificity 0.83,
      positive predictive value 0.92 and negative predictive value 0.92. Of the CMR
      components, perfusion deficit was the strongest independent predictor (odds ratio
      132.3, p < 0.0001). CONCLUSION: In a great number of patients being referred to
      cath lab with ACC/AHA class II indication for CXA, CMR provides a high accuracy
      for decision making regarding appropriateness of the invasive exam. CMR prior to
      CXA could substantially reduce pure diagnostic coronary angiographies in patients
      with intermediate probability for CAD, in our patient-cohort from approximately
      34% to 6%. Further studies are warranted to identify rare false negative CMR
      results.

PMID- 16897143
TI  - Inflammation, ECG changes and pericardial effusion: whom to biopsy in suspected
      myocarditis?
AB  - The role of endomyocardial biopsies in patients with clinically suspected acute
      myocarditis, myocarditis in the past, and dilated cardiomyopathy is discussed
      controversially. In fact, it is still under discussion whether information
      obtained from endomyocardial biopsies is relevant for further clinical decisions.
      Therefore this Critical Perspective will deal with the question, which patient
      should undergo endomyocardial biopsy investigations for an etiopathogenic
      differentiation of the disease and for the possible choice of immunomodulatory
      treatment strategies.

PMID- 16897146
TI  - Simultaneous angiographic late stent thrombosis in two different coronary vessels
      after withdrawal of the combined anti-platelet therapy.

PMID- 16897147
TI  - Late pacemaker twiddler syndrome.

PMID- 16897149
TI  - [Acupuncture. Clinical studies on efficacy and effectiveness in patients with
      chronic pain].
AB  - In Germany, acupuncture is one of the most frequently used complementary and
      alternative therapies. In the year 2000, we initiated three large projects in co
      operation with statutory health insurance companies to assess the effectiveness,
      safety and costs of acupuncture in patients with chronic headache, low back pain
      and pain due to osteoarthritis. Our findings showed that acupuncture was more
      effective than conventional standard treatment, treatment without acupuncture or
      a waiting list control. A significant difference between acupuncture and sham
      acupuncture was only seen for arthritis of the knee; for the other diagnoses,
      both forms of acupuncture showed similar effects. Whether the effects of
      acupuncture are due primarily to specific or unspecific mechanisms appears to
      depend on the diagnosis and should be investigated in further studies.

PMID- 16897150
TI  - Could neuroimaging help us to interpret the clinical effects of acupuncture?
AB  - One of the problems in assessing acupuncture efficacy has been the lack of a
      standardised placebo/control. Despite the lack of 'proof', acupuncture is widely
      used; hence it would seem that a large proportion of the public are not too
      concerned with the question of efficacy. Patients and researchers approach the
      issue of whether acupuncture "works" in an entirely different way. It may be that
      the management of chronic pain as a whole is largely context driven and non
      specific. Therefore, research should focus on areas such as pragmatic/comparative
      trials and the non-specific effects of treatment. Improving our understanding of
      the neural mechanisms and substrates of acupuncture, placebo and non-specific
      effects might enable us to better define a "true placebo" and improve trial
      design. Imaging studies, however, need to be much more pragmatic. Because of the
      large overlap in areas of brain activated through acupuncture, pain, placebo and
      non-specific factors, separating these out in an attempt to pinpoint the
      mechanisms behind acupuncture will be difficult. Ultimately we need a balance
      between efficacy, comparative and mechanistic trials using imaging work to inform
      the whole picture. A broader view of research is therefore necessary to yield
      meaningful answers and we need to look at the whole package that acupuncture
      delivers.

PMID- 16897151
TI  - [Glycotoxins and cellular dysfunction. A new mechanism for understanding the
      preventive effects of lifestyle modifications].
AB  - Recently the AGE-RAGE interaction was identified as a potential mechanism
      underlying chronic and inflammatory diseases like atherosclerosis, diabetes
      mellitus and kidney disease. Advanced glycation end products (AGEs) are the
      derivatives of glucose-protein or glucose-lipid reactions and are mainly
      generated from the diet (depending on intensity of heating, cooking time and
      oxygenation). Binding of AGEs or other ligands to the AGE receptor (RAGE) results
      in cellular activation, i.e. increased expression of inflammatory mediators and
      oxidative stress. Diet-derived AGEs thus induce deleterious effects on tissues
      and the cardiovascular system. Recent research also found that other lifestyle
      factors are associated with pronounced inflammatory activation, e.g. psychosocial
      stress and smoking. In addition, each intake of meals is associated with
      proinflammatory cellular changes. The AGE-RAGE model and investigations of the
      underlying cellular mechanisms thus may lead to a better understanding of the
      health benefits of diets (Mediterranean diet, uncooked vegetarian diets), caloric
      restriction and intermittent fasting. The clinical impact of low-AGE diets and
      fasting and the interaction between stress and food intake should be further
      investigated in controlled trials.

PMID- 16897152
TI  - [Implementation of the new drinking water regulation section sign 18: monitoring
      of drinking water systems in houses--water for public use].
AB  - The monitoring of drinking water based on the drinking water regulation is one of
      the central tasks of public health authorities in Germany. With the coming into
      force of the new drinking water regulation in the year 2003 also water supply
      plants "from which water is made available for the public, in particular in
      schools, kindergartens, hospitals, restaurants and other communal facilities"
      must be supervised for the first time (TrinkwV section sign 18). Thus, for
      Frankfurt/Main the number of the facilities/objects which are to be supervised
      rose from approx. 300 to approx. 4,700. Since appropriate expansion of personnel
      was not possible, innovative solutions were in demand for implementation of these
      tasks. These are introduced here.

PMID- 16897153
TI  - [Red blood cell count in relation to exposure to mobile radio facilities : Report
      of the commission on "methods and quality assurance in environmental medicine"].

PMID- 16897154
TI  - [Recommendations by the Federal Environmental Agency relative to the aeration of
      indoor pools. Recommendations by the Federal Environmental Agency after a hearing
      with the Commission on Swimming Pools and Spas of the Federal Health Ministry
      (BMG) at the Federal Environmental Agency].

PMID- 16897158
TI  - Probucol decreases asymmetrical dimethylarginine level by alternation of protein
      arginine methyltransferase I and dimethylarginine dimethylaminohydrolase
      activity.
AB  - HYPOTHESIS: Asymmetric dimethylarginine (ADMA), an endogenous nitric oxide
      synthase inhibitor (NOS), may play an important role in endothelium dysfunction.
      Probucol, a potent antioxidant drug, may improve endothelium function via
      reduction of NOS inhibitor level. The present study examined whether the
      decreased level of ADMA by probucol is related to enhancement of protein arginine
      methyltransferase I (PRMT I) expression and reduction of dimethylarginine
      dimethylaminohydrolase (DDAH) activity. METHODS: Endothelial cells were cultured
      and used for all these studies. ADMA concentration and DDAH activity were
      determined by HPLC. Expression of PRMT I and eNOS were characterized by western
      blot. RESULTS: Pretreatment with oxidized-low density lipoprotein (ox-LDL) (10,
      30 or 100 microg/ml) or lysophosphatidylcholine (LPC) (1.0, 2.5 or 5.0 microg/ml)
      for 12, 24 or 48 h markedly increased the activity of lactate dehydrogenase (LDH)
      in cultured endothelial cell. Incubation ofendothelial cells with ox-LDL (100
      microg/ml) or LPC (5.0 microg/ml) for 48 h significantly increased the expression
      of PRMT I, and levels of MDA and ADMA, and decreased the concentration of
      nitrite/nitrate, the expression of eNOS and the activity of DDAH. Probucol
      significantly decreased the level of ADMA, concomitantly with reduction of PRMT I
      expression and elevation of DDAH activity and up-regulation of eNOS expression.
      CONCLUSION: In summary, the present results suggest that the protective effect of
      probucol on endothelium is related to reduction of ADMA concentration by
      inhibition of PRMT I expression and enhancement of DDAH activity.

PMID- 16897160
TI  - Adhesion of slime producing Staphylococcus epidermidis strains to PVC and diamond
      like carbon/silver/fluorinated coatings.
AB  - Staphylococcus epidermidis has emerged as a pathogen associated with infections
      of implanted medical devices. Bacterial adhesion is a crucial step in infection
      on biomaterial surfaces. To quantitatively determine the relationship between
      poly (vinyl chloride) (PVC) surface properties and bacterial adhesion, we have
      compared attachment of slime-producing S. epidermidis strains on PVC and various
      coatings under flow conditions. Bacterial adhesion and colonization was
      quantified by counting the viable organisms on the adherent surface as well as by
      scanning electron microscopy, epifluorescence microscopy and atomic force
      microscopy. Fluorination of the PVC surface encourages S. epidermidis adhesion
      whereas; diamond-like carbon (DLC) and especially silver (Ag) coatings seem to
      inhibit its adhesion. In most materials, the number of adherent bacteria
      decreased with the increase of shear rate. These results indicate that bacterial
      adhesion is influenced by the chemical properties of the polymeric surfaces, the
      surface roughness and the associated flow conditions.

PMID- 16897161
TI  - Preparation of fluoride-substituted hydroxyapatite by a molten salt synthesis
      route.
AB  - Fluoride-substituted hydroxyapatite (FHAp) with high thermal and morphologic
      stability was successfully prepared by a molten salt synthesis route. XRD
      patterns and FTIR spectra identified the synthesized powders as FHAp solid
      solution. The FHAp obtained with potassium sulfate as the flux showed the rod
      like morphology without detectable decomposition up to 1300 degrees Celsius and
      the flux, sodium sulfate, led to the spheriodal FHAp. After investigating the
      effects of salt species on the FHAp morphologies, it was found that solubility
      was not the exclusive factor, which affected the morphological development of
      apatite powders, and the cations of molten salt species also played an important
      role.

PMID- 16897162
TI  - Effect of carbonate content and buffer type on calcium phosphate formation in SBF
      solutions.

PMID- 16897163
TI  - Study of yttrium containing bioactive glasses behaviour in simulated body fluid.
AB  - The influence of yttrium oxide on the bioactivity of glasses in the system SiO(2)
      Na(2)O-P(2)O(5)-CaO-B(2)O(3)-K(2)O-MgO was studied in a simulated body fluid
      (SBF). Two series of glasses with different bioactivity were investigated. The
      reaction layers formed on the surface of the exposed glasses were evaluated by
      means of back scattered electron imaging of scanning electron microscopy equipped
      with energy dispersive X-ray analysis (BEI-SEM/EDXA). The concentration of Y, Ca
      and P released from the glasses into SBF, during 21 days was determined using
      inductively coupled plasma-emission spectroscopy ICP-AES and inductively coupled
      plasma-mass spectroscopy ICP-MS. Introducing yttrium in the selected bioactive
      glass tended to diminish the bioactivity of the glasses. The thickness of the
      calcium phosphate layer decreased with increasing yttrium oxide content. The same
      effect was also observed when yttrium oxide partially replaced only calcium,
      magnesium and phosphorous oxide in the precursor glass. The data show that we can
      produce bioactive glasses with yttrium oxide as a component. By suitable
      tailoring of the rest of the glasses the yttrium effect on the glass behavior in
      SBF should be possible to control and thus produce yttrium containing glasses
      with desired bioactivity.

PMID- 16897164
TI  - Electron microscopic investigation on the osteogenesis at titanium implant/bone
      marrow interface under masticatory loading.
AB  - Electron microscopic investigation on osteogenetic process at the implant surface
      of threadless rod-type titanium implants with different surface roughness of Ra
      0.4 +/- 0.01 microm, Sm 2.6 +/- 0.3 microm and Ra 2.0 +/- 0.12 microm, Sm 36 +/-
      9.1 microm was performed at the early stage of 21 and 42 days post implantation
      into the jawbones of four beagles under the load bearing condition of functional
      mastication. The implant surfaces were covered with a blood clot and
      haematopoietic stem cells (HSC) including phagocytic monocytes immediately after
      the implantation. Successively, osteogenic stem cells (OSC) migrated from
      cortical and/or trabecular endosteum to the HSC-layer on the implant surface. The
      new bone formation at the implant/bone marrow interface was developed by
      collaboration of osteomediator cells (OMC) differentiated from monocytes of HSC
      and osteoblast phenotype cells of OSC derived from endosteum of cortical bone
      and/or trabecular. The new bone layer at the implant surface consisted of two
      layers, solution-mediated calcification layer of pseudo bone and cell
      (osteoblast) -mediated calcification layer of true bone. The pseudo bone was
      produced by solution-mediated calcification of OMC- and HSC-remnants near by the
      implant surface. The bone healing process at the implant/bone marrow interface
      depended upon two factors; the migration of OSC from cortical and/or trabecular
      endosteum to the implant surface and the healing potentiality. Topographic
      dependency upon the bone healing potential at implant/bone marrow interface was
      not confirmed in this experiment under the load bearing condition of functional
      mastication.

PMID- 16897165
TI  - No evidence to indicate topographic dependency on bone formation around cp
      titanium implants under masticatory loading.
AB  - In vitro studies have proved the topographic dependency upon osteogenesis on
      titanium plate by investigating the cell-adhesion, -shape, -proliferation, 
      differentiation, ALP activity and osteocalcin production of osteogenic stem
      cells, MG36, MC3T3-E1 and wild strains of bone formative cells from animal and
      human. However, this in vivo study on bone growth around cp titanium dental
      implants under masticatory loading did not demonstrate significant difference
      among the different surface roughness in the range of Ra 0.4-1.9 microm, Rz 2.8
      11.2 microm, Rmax 3.6-28.1 microm and Sm 2.9-41.0 microm, which was estimated by
      measuring the bone contacts, bone occupancies and bone bonding strengths at the
      implant/bone marrow interface. It is revealed that the topographic dependency on
      the osteogenetic activity is apt to be covered with wide variation in bone
      healing potential under the clinical condition with functional biting load.

PMID- 16897166
TI  - Enhancing angiogenesis in collagen matrices by covalent incorporation of VEGF.
AB  - Since the survival of ingrowing cells in biomaterials for regenerative processes
      largely depends on the supply of nutrients and oxygen, angiogenesis plays an
      important role in the development of new materials for tissue engineering. In
      this study we investigated the possibility of enhancing the angiogenic properties
      of collagen matrices by covalent incorporation of the vascular endothelial growth
      factor (VEGF). In a previous paper we already reported the use of homo- and
      heterobifunctional cross-linking agents for modifying collagen matrices [1]. In
      the present work the angiogenic growth factor was linked to the collagen with the
      homobifunctional cross-linker disuccinimidyldisuccinatepolyethyleneglycol (SS-PEG
      SS) in a two step procedure. The efficiency of the first reaction step-the
      reaction of SS-PEG-SS with VEGF--was evaluated by western blot analysis. After 10
      minutes virtually all of the dimeric molecules VEGF were on average modified by
      conjugation with 1 cross-linking molecule. The biological activity of the
      conjugate was investigated by exposing endothelial cells to non-modified VEGF and
      to VEGF conjugated to the cross-linker. The conjugation only had a limited effect
      on the mitogenic activity of VEGF. We therefore applied the cross-linking
      reaction to the VEGF-collagen system. In a first approach the changes were
      evaluated by the in vitro exposure of HUVECs to non-modified matrices, to
      matrices in which the VEGF was simply admixed and to matrices in which the VEGF
      was covalently incorporated. The angiogenic properties were evaluated in vivo
      with the chorioallantois membrane model. In this assay the chorioallantois
      membrane of the chicken embryo was exposed to the same set of matrices. The
      covalent incorporation of VEGF has a small but significant effect both on the
      formation of microvessels in the chorioallantois membrane and the tissue ingrowth
      into the implant. The covalent incorporation of angiogenic growth factors may
      thus be considered as a promising approach for enhancing the angiogenic
      capabilities of collagen matrices. Also the cross-linking with the
      homobifunctional cross-linking agent has a positive effect on the angiogenic
      potential of the collagen matrices.

PMID- 16897167
TI  - Improved mechanical properties of acrylic bone cement with short titanium fiber
      reinforcement.
AB  - Acrylic bone cements are widely used in total joint arthroplasties to grout the
      prosthesis to bone. The changes in the tensile properties and fracture toughness
      of polymethylmethacrylate (PMMA) bone cements obtained by the addition of control
      and heat treated short titanium fibers are studied. Heat treatment of titanium
      fibers is conducted to precipitate titania particles on the fiber surface, which
      may improve the biocompatibility of the metal. Control (non-heat treated) and
      heat treated short titanium fibers (250 microm long and 20microm diameter) were
      used as reinforcements at 3 volume %. X-ray diffraction indicated the presence of
      a rutile form of titania due to the heat treatments. Results indicate that the
      tensile and fracture properties of unfilled bone cement were improved by the
      addition of control and heat-treated fibers. The fracture properties of bone
      cements reinforced with control titanium fibers were at least 10% higher than
      those reinforced with heat treated titanium fibers. Therefore, we recommend
      further studies on the use of non-heat treated titanium fibers to reinforce
      acrylic bone cement.

PMID- 16897168
TI  - Biocompatibility of poly (3-hydroxybutyrate-co-3-hydroxyhexanoate) modified by
      silk fibroin.

PMID- 16897169
TI  - Artificial midline-fascia of the human abdominal wall for testing suture
      strength.
AB  - To reduce testing of human abdominal wall closure-modalities in test animals, a
      fibre reinforced rubber with identical mechanical properties compared to the
      human midline fascia (linea alba: LA) was developed. The microscopic structure of
      the human LA, stress-strain behaviour, maximum tensile force and macroscopic
      failure mechanism in tensile tests with human LA were defined as indicators for
      the required properties of the fibre reinforced rubber. A composite consisting of
      latex rubber and cotton fibres was developed that shows mechanical properties
      comparable to the human abdominal wall. The results of the tensile tests on
      sutured artificial LA were highly similar to those performed on sutured human LA.
      The material presented in this study is proposed as a substitute for human and
      animal tissues presently used to test suture techniques. A protocol for an
      approach to develop artificial fibrous soft tissue like fascie and tendon was
      drawn up.

PMID- 16897170
TI  - Preparation of bioelectret collagen and its influence on cell culture in vitro.
AB  - Collagen extracted from pigskin was corona-charged negatively by a specifically
      designed device. Different charging voltages, temperatures and times were applied
      to prepare collagen bioelectret. The decline of the surface potential of the
      bioelectret under different treatment was then determined. The data showed that
      the surface potential was markedly varied with the charging conditions. The
      optimal values of three parameters for charging collagen coatings were defined as
      follows: voltage, 8 KV; temperature, 40 degrees Celsius; time, 25 min. Treatment
      of the bioelectret with distillated water, or saline solution (0.9%) or culture
      medium induced a sharp decrease of the surface potential. In addition, we
      investigated the effects of the charged collagen on cell growth and intracellular
      calcium level of three types of cultured mammalian cell lines, including Chinese
      hamster ovary CHO cells, human cervix uteri tumor HeLa cells and human
      promyelocytic HL-60 cells. Cell growth and the intracellular calcium level were
      determined by MTT reagent-based assay and a fluorescent probe Fura-2,
      respectively. The results showed that negatively charged collagen stimulated the
      growth of CHO or HL-60 cell line but inhibited the growth of HeLa cell line.
      Furthermore, after attaching to the charged collagen, the intracellular calcium
      level of CHO cells increased, while that of HeLa cells decreased. Thus we
      proposed for the first time that collagen bioelectret could differentially
      modulate the growth of different cells, by an unknown mechanism that probably
      involves a role of intracellular calcium.

PMID- 16897171
TI  - Introduction. Professor Yasuo Inoue: 1934-2005.

PMID- 16897172
TI  - KDN (deaminated neuraminic acid): dreamful past and exciting future of the newest
      member of the sialic acid family.
AB  - KDN is an abbreviation for 2-keto-3-deoxy-D-glycero-D-galacto-nononic acid, and
      its natural occurrence was revealed in 1986 by a research group including the
      present authors. Since sialic acid was used as a synonym for N-acylneuraminic
      acid at that time, there was an argument if this deaminated neuraminic acid
      belongs to the family of sialic acids. In this review, we describe the 20 years
      history of studies on KDN (KDNology), through which KDN has established its
      position as a distinct member of the sialic acid family. These studies have
      clarified that: (1) KDN occurs widely among vertebrates and bacteria similar to
      the occurrence of the more common sialic acid, N-acetylneuraminic acid (Neu5Ac),
      but its abundant occurrence in animals is limited to lower vertebrates. (2) KDN
      is found in almost all types of glycoconjugates, including glycolipids,
      glycoproteins and capsular polysaccharides. (3) KDN residues are linked to almost
      all glycan structures in place of Neu5Ac. All linkage types known for Neu5Ac;
      alpha2,3-, alpha2,4-, alpha2,6-, and alpha2,8- are also found for KDN. (4) KDN is
      biosynthesized de novo using mannose as a precursor sugar, which is activated to
      CMP-KDN and transferred to acceptor sugar residues. These reactions are catalyzed
      by enzymes, some of which preferably recognize KDN, but many others prefer Neu5Ac
      to KDN. In addition to these basic findings, elevated expression of KDN was found
      in fetal human red blood cells compared with adult red blood cells, and ovarian
      tumor tissues compared with normal controls. KDNase, an enzyme which specifically
      cleaves KDN-linkages, was discovered in a bacterium and monoclonal antibodies
      that specifically recognize KDN residues in KDNalpha2,3-Gal- and KDNalpha2,8-KDN
      linkages have been developed. These have been used for identification of KDN
      containing molecules. Based on past basic studies and variety of findings, future
      perspective of KDNology is presented.

PMID- 16897174
TI  - Ganglioside GD1a regulation of caveolin-1 and Stim1 expression in mouse FBJ
      cells: augmented expression of caveolin-1 and Stim1 in cells with increased GD1a
      content.
AB  - GD1a was previously shown responsible for regulating cell motility, cellular
      adhesiveness to vitronectin, phosphorylation of c-Met and metastatic ability of
      mouse FBJ osteosarcoma cells. To determine the particular molecules regulated by
      GD1a, FBJ cells were assessed for tumor-related gene expression by semi
      quantitative RT-PCR. Caveolin-1 and stromal interaction molecule 1 (Stim1)
      expression in FBJ-S1 cells, rich in GD1a, were found to be 6 and 4 times as much,
      respectively, than in FBJ-LL cells devoid of GD1a. Enhanced production of
      caveolin-1 in protein was confirmed by Western blotting. A low-metastatic FBJ-LL
      cell variant, having high GD1a expression through beta1-4GalNAcT-1 (GM2/GD2
      synthase) cDNA transfection (Hyuga S, et al, Int J Cancer 83: 685-91, 1999),
      showed enhanced production of caveolin-1 and Stim1 in mRNA and protein, compared
      to mock-transfectant M5. Incubation of FBJ-M5 cells with exogenous GD1a augmented
      the expression of caveolin-1 in mRNA and protein and Stim1 in mRNA as well.
      Treatment of FBJ-S1 with fumonisin B1, an inhibitor of N-acylsphinganine
      synthesis, for 15 days caused the complete depletion of gangliosides and
      suppressed the expression of caveolin-1 and Stim1. St3gal5 siRNA transfected
      cells showed decreased expression of caveolin-1 and Stim1 mRNA, as well as
      St3gal5 mRNA. These findings clearly indicate ganglioside GD1a to be involved in
      the regulation of the transformation suppressor genes, caveolin-1 and Stim1.
      Moreover, treatment with GD1a of mouse melanoma B16 cells and human hepatoma
      HepG2 cells brought about elevated expression of caveolin-1 and Stim1.

PMID- 16897175
TI  - Carbohydrate ligands of human C-reactive protein: binding of neoglycoproteins
      containing galactose-6-phosphate and galactose-terminated disaccharide.
AB  - Binding of carbohydrate ligand by human C-reactive protein (CRP), in both native
      form and structurally deviated form (neoCRP or mCRP), was investigated using
      galactose-6-phosphate (Gal6P)- and Galbeta3GalNAc-containing bovine serum albumin
      (BSA) derivatives. To this end, we synthesized glycosides of Gal6P and
      Galbeta3GalNAc that can potentially generate a terminal aldehyde group. omega
      Aldehydo glycosides were then conjugated to BSA via reductive amination. Using
      these neoglycoproteins, we showed that: (1) Gal6P-BSA and Galbeta3GalNAc-BSA
      bound to both forms of CRP, the former with or without calcium and the latter
      only in the absence of calcium; (2) phosphate-containing ligands can be bound
      with or without calcium, but the binding is much stronger in the presence of
      calcium than in the absence, underscoring the importance of direct coordination
      of phosphate to two calcium ions observed in the X-ray structure of
      phosphorylcholine (PC)-CRP complex; (3) cross-inhibition studies further
      corroborated the hypothesis that binding sites of PC and sugar are contiguous;
      (4) while PC-BSA bound to the native CRP over a wide pH range of 4.5 to 9, all
      the carbohydrate ligands and protamine-BSA (poly-cation-based ligand) exhibited
      optimal binding at around pH 6 to 6.5; and (5) ligand-binding conformation of
      mCRP appears to be more fragile than that of the native CRP in the acidic media
      (pH < 6).

PMID- 16897173
TI  - Free N-linked oligosaccharide chains: formation and degradation.
AB  - There is growing evidence that N-linked glycans play pivotal roles in protein
      folding and intra- and/or intercellular trafficking of N-glycosylated proteins.
      It has been shown that during the N-glycosylation of proteins, significant
      amounts of free oligosaccharides (free OSs) are generated in the lumen of the
      endoplasmic reticulum (ER) by a mechanism which remains to be clarified. Free OSs
      are also formed in the cytosol by enzymatic deglycosylation of misfolded
      glycoproteins, which are subjected to destruction by a cellular system called "ER
      associated degradation (ERAD)." While the precise functions of free OSs remain
      obscure, biochemical studies have revealed that a novel cellular process enables
      them to be catabolized in a specialized manner, that involves pumping free OSs in
      the lumen of the ER into the cytosol where further processing occurs. This
      process is followed by entry into the lysosomes. In this review we summarize
      current knowledge about the formation, processing and degradation of free OSs in
      eukaryotes and also discuss the potential biological significance of this
      pathway. Other evidence for the occurrence of free OSs in various cellular
      processes is also presented.

PMID- 16897176
TI  - Synthesis and enzymatic susceptibility of a series of novel GM2 analogs.
AB  - A series of GM2 analogs in which GM2 epitope was coupled to a variety of glycosyl
      lipids were designed and synthesized to investigate the mechanism of enzymatic
      hydrolysis of GM2 ganglioside. The coupling of N-Troc-protected sialic acid and p
      methoxyphenyl galactoside acceptor gave the crystalline disaccharide, which was
      further coupled with galactosamine donor to give the desired GM2 epitope
      trisaccharide. After conversion into the corresponding glycosyl donor, the
      trisaccharide was coupled with galactose, glucose and artificial ceramide (B30)
      to give the final compounds. The result on hydrolysis of GM2 analogs indicates
      that GM2 activator protein requires one spacer sugar between GM2 epitope and the
      lipid moiety to assist the hydrolysis of the terminal GalNAc residue.

PMID- 16897177
TI  - Glycomic studies of Drosophila melanogaster embryos.
AB  - With the complete genome sequence of Drosophila melanogaster defined a systematic
      approach towards understanding the function of glycosylation has become possible.
      Structural assignment of the entire Drosophila glycome during specific
      developmental stages could provide information that would shed further light on
      the specific roles of different glycans during development and pinpoint the
      activity of certain glycosyltransferases and other glycan biosynthetic genes that
      otherwise might be missed through genetic analyses. In this paper the major
      glycoprotein N- and O-glycans of Drosophila embryos are described as part of our
      initial undertaking to characterize the glycome of Drosophila melanogaster. The N
      glycans are dominated by high mannose and paucimannose structures. Minor amounts
      of mono-, bi- and tri-antennary complex glycans were observed with GlcNAc and
      Galbeta1-4GlcNAc non-reducing end termini. O-glycans were restricted to the mucin
      type core 1 Galbeta1-3GalNAc sequence.

PMID- 16897178
TI  - Distinctive characteristics of MALDI-Q/TOF and TOF/TOF tandem mass spectrometry
      for sequencing of permethylated complex type N-glycans.
AB  - Concerted MALDI-MS profiling and CID MS/MS sequencing of permethylated glycans is
      one of the most effective approaches for high throughput glycomics applications.
      In essence, the identification of larger complex type N-glycans necessitates an
      unambiguous definition of any modification on the trimannosyl core and the
      complement of non-reducing terminal sequences which constitute the respective
      antennary structures. Permethylation not only affords analyses of both neutral
      and sialylated glycans at comparable ease and sensitivity but also yields more
      sequence-informative fragmentation pattern. Facile glycosidic cleavages directed
      mostly at N-acetylglucosamine under low energy CID, as implemented on a
      quadrupole/time-of-flight (Q/TOF) instrument, often afford multiple losses of the
      attached antenna resulting in characteristic ions related to the number of
      antennary branches on the trimannosyl core. Non-reducing terminal epitopes can be
      easily deduced but information on the linkage specific substituent on the
      terminal units is often missing. The high energy CID MS/MS afforded by TOF/TOF
      instrument can fill in the gap by giving an array of additional cross-ring and
      satellite ions. Glycosidic cleavages occurring specifically in concert with loss
      of 2-linked or 3-linked substituents provide an effective way to identify the
      branch-specific antennary extension. These characteristics are shown here to be
      effective in deriving the sequences of additionally galactosylated, sialylated
      and fucosylated terminal N-acetyllactosamine units and their antennary location.
      Together, a highly reproducible fragmentation pattern can be formulated to
      simplify spectral assignment. This work also provides first real examples of
      sequencing multiply sialylated complex type N-glycans by high energy CID on a
      TOF/TOF instrument.

PMID- 16897179
TI  - A 1H STD NMR spectroscopic investigation of sialylnucleoside mimetics as probes
      of CMP-Kdn synthetase.
AB  - CMP-Kdn synthetase catalyses the reaction of sialic acids (Sia) and CTP to the
      corresponding activated sugar nucleotide CMP-Sia and pyrophosphate PP( i ).
      Saturation Transfer Difference (STD) NMR spectroscopy has been employed to
      investigate the sub-structural requirements of the enzyme's binding domain.
      Sialylnucleoside mimetics, where the sialic acid moiety has been replaced by a
      carboxyl group and a hydrophobic moiety, have been used in NMR experiments, to
      probe the tolerance of the CMP-Kdn synthetase to such replacements. From our data
      it would appear that unlike another sialylnucleotide-recognising protein, the CMP
      Neu5Ac transport protein, either a phosphate group or other functional groups on
      the sialic acid framework may play important roles in recognition by the
      synthetase.

PMID- 16897180
TI  - Structure elucidation of NeuAc, NeuGc and Kdn-containing O-glycans released from
      Triturus alpestris oviductal mucins. Characterization of the poly LacdiNAc
      sequence: HSO3(4)(GalNAcbeta1-4GlcNAcbeta1-3)1-3GalNAcbeta1-4(GlcNAcbeta1-3)0
      1GlcNAcbeta1-6GalNAc-ol.
AB  - Eggs from Amphibia are surrounded by several layers of jelly that are needed for
      proper fertilization. Jelly coat is composed of highly glycosylated mucin-type
      glycoproteins containing up to 60% of carbohydrates, which display a remarkable
      species-specificity. This material obtained from Triturus alpestris was submitted
      to reductive beta-elimination and the released oligosaccharide-alditols were
      further fractionated by HPLC. Structural characterization was performed through a
      combination of two dimensional (1)H-(1)H and (1)H-(13)C NMR and ESI-MS/MS
      analysis. Numerous carbohydrate chains are characterized by the presence of the
      Cad (Sd(a)) determinant, including respectively NeuAc, NeuGc or Kdn as a sialic
      acid. But the most significant O-glycan sequences which mark the difference
      between the jelly of T. alpestris and other studies amphibian jellies are
      polymers of GalNAc(beta 1-4)GlcNAc (LacdiNAc) which form part of the following
      sequence: HSO(3)(4)(GalNAcbeta 1-4GlcNAcbeta 1-3)(1-3)GalNAcbeta 1-4(GlcNAcbeta 1
      3)(0-1)GlcNAcbeta 1-6GalNAc-ol.

PMID- 16897181
TI  - Identification and partial characterization of soluble and membrane-bound
      KDN(deaminoneuraminic acid)-glycoproteins in human ovarian teratocarcinoma PA-1,
      and enhanced expression of free and bound KDN in cells cultured in mannose-rich
      media.
AB  - KDN (Deaminoneuraminic acid, or deaminated neuraminic acid) is a minor but
      biosynthetically independent member of the sialic acid. Human occurrence of KDN
      has already been established, although its level is so little that it is often
      undetectable by conventional sialic acid analysis. Elevated expression of KDN in
      fetal cord blood cells and some malignant tumor cells have been reported.
      However, in mammalian cells and tissues KDN mostly occurs as the free sugar and
      little occurred conjugated to glycolipids and/or glycoproteins. A positive
      correlation between the ratio of free KDN/free Neu5Ac in ovarian adenocarcinomas
      and the stage of malignancy has been noted for diagnostic use. We hypothesized
      that elevated expression of KDN in mammalian systems may be closely related to
      elevated activities of enzymes involved in the formation of sialoglycoconjugates
      and/or aberrant supply of the precursor sugar, mannose, used in the biosynthesis
      of KDN. In this study we used human ovarian teratocarcinoma cells PA-1 to further
      analyze KDN expression in human cells. Major findings reported in this paper are,
      (i) a 30 kDa KDN-glycoprotein immunostainable with monoclonal antibody,
      mAb.kdn3G, (specific for the KDNalpha2 --> 3Galbeta1--> epitope) and sensitive to
      KDNase was identified in the membrane fraction of the cell: (ii) a 49 kDa KDN
      glycoprotein that is not reactive with mAb.kdn3G but is sensitive to KDNase was
      identified in the soluble fraction: and (iii) PA-1 cells showed unique response
      to mannose added to the growth medium in that the levels of both free and bound
      forms of KDN are elevated. This is the first report on the identification of
      mammalian KDN-glycoproteins by chemical and biochemical methods.

PMID- 16897182
TI  - Oral ingestion of mannose alters the expression level of deaminoneuraminic acid
      (KDN) in mouse organs.
AB  - Deaminoneuraminic acid (KDN) is a unique member of the sialic acid family. We
      previously demonstrated that free KDN is synthesized de novo from mannose as its
      precursor sugar in trout testis, and that the amount of intracellular KDN
      increases in mouse B16 melanoma cells cultured in mannose-rich media [Angata et
      al. (1999) J. Biol. Chem. 274, 22949-56; Angata et al. (1999) Biochem. Biophys.
      Res. Commun. 261, 326-31]. In the present study, we first demonstrated a mannose
      induced increase in intracellular KDN in various cultured mouse and human cell
      lines. These results led us to examine whether KDN expression in mouse organs is
      altered by exogenously administered mannose. Under normal feeding conditions,
      intracellular free KDN was present at very low levels (19-48 pmol/mg protein) in
      liver, spleen, and lung, and was not detected in kidney or brain. Oral ingestion
      of mannose, both short-term (90 min) and long-term (2 wk), resulted in an
      increase of intracellular KDN up to 60-81 pmol/mg protein in spleen and lung and
      6.9-18 pmol/mg protein in kidney and brain; however, no change was observed in
      liver. The level of KDN in organs appears not to be determined only by the KDN 9
      phosphate synthase activity, but might also be affected by other enzymes that
      utilize mannose 6-phosphate as a substrate as well as the enzymes that breakdown
      KDN, like KDN-pyruvate lyase. In blood, the detectable amount of free KDN did not
      change on oral ingestion of mannose. These findings indicate that mannose in the
      diet affects KDN metabolism in various organs, and provide clues to the mechanism
      of altered KDN expression in some tumor cells and aged organs.

PMID- 16897183
TI  - Molecular basis for polysialylation: a novel polybasic polysialyltransferase
      domain (PSTD) of 32 amino acids unique to the alpha 2,8-polysialyltransferases is
      essential for polysialylation.
AB  - To determine the molecular basis of eukaryotic polysialylation, the function of a
      structurally unique polybasic motif of 32 amino acids (pI approximately 12) in
      the polysialyltransferases (polySTs), ST8Sia II (STX and ST8Sia IV (PST) was
      investigated. This motif, designated the "polysialyltransferase domain" (PSTD),
      is immediately upstream of the sialylmotif S (SM-S). PolyST activity was lost in
      COS-1 mutants in which the entire PSTD in ST8Sia IV was deleted, or in mutants in
      which 10 and 15 amino acids in either the N- or C- terminus of PSTD were deleted.
      Site-directed mutagenesis showed that Ile(275), Lys(276) and Arg(277) in the C
      terminus of PSTD in ST8Sia IV, which is contiguous with the N-terminus of
      sialylmotif-S, were essential for polysialylation. Arg(252) in the N-terminus
      segment of the PSTD was also required, as was the overall positive charge. Thus,
      multiple domains in the polySTs can influence their activity. Immunofluorescent
      microscopy showed that the mutated proteins were folded correctly, based on their
      Golgi localization. The structural distinctness of the conserved PSTD in the
      polySTs, and its absence in the mono- oligoSTs, suggests that it is a
      "polymerization domain" that distinguishes a polyST from a
      monosialyltransferases. We postulate that the electrostatic interaction between
      the polybasic PSTD and the polyanionic polySia chains may function to tether
      nascent polySia chains to the enzyme, thus facilitating the processive addition
      of new Sia residues to the non-reducing end of the growing chain. In accord with
      this hypothesis, the polyanion heparin was shown to inhibit recombinant human
      ST8Sia II and ST8Sia IV at 10 microM.

PMID- 16897184
TI  - Screening a series of sialyltransferases for possible BACE1 substrates.
AB  - Deposition of amyloid beta-peptide (Abeta) and neurofibrillary tangles in the
      brain are hallmarks of Alzheimer's disease (AD) pathogenesis. BACE1, a membrane
      bound aspartic protease that cleaves amyloid precursor protein (APP) to produce
      Abeta, has been implicated in triggering the pathogenesis of the disease. We
      previously reported that BACE1 also cleaved alpha2,6-sialyltransferase (ST6Gal I)
      in the Golgi apparatus and induced its secretion from the cell. Since most
      glycosyltransferases show Golgi localization and many of these are cleaved and
      secreted from the cell, we hypothesized that other glycosyltransferases may also
      be BACE1 substrates. Here, we focused on a series of sialyltransferases as
      candidates for BACE1 substrates. We found that BACE1 cleaved
      polysialyltransferase ST8Sia IV (PST) in vitro. We further found that BACE1
      overexpression in COS cells enhanced the secretion of ST3Gal I, II, III and IV,
      although these sialyltransferases were not cleaved by BACE1 in vitro. These
      results suggest that BACE1 expression affects glycosylation not only by directly
      cleaving glycosyltransferases but also by modifying the secretion of
      glycosyltransferases via some other mechanisms.

PMID- 16897185
TI  - Preferential reduction of the alpha-2-6-sialylation from cell surface N-glycans
      of human diploid fibroblastic cells by in vitro aging.
AB  - Human diploid fibroblastic cell line, TIG-3, has a finite life span of about 80
      population doubling levels (PDL), and is used for in vitro aging studies. Young
      cells (PDL 23) grew to higher cell densities at a higher growth rate than aged
      cells (PDL 77). When the electrophoretic mobility of cells was determined, the
      negative surface charge of the aged cells decreased significantly when compared
      to that of young cells. Lectin blot analysis of membrane glycoproteins showed
      that the alpha-2-6-sialylation but not the alpha-2-3-sialylation of N-glycans
      decreases markedly in the aged cells when compared to the young cells. In support
      of this observation, the cDNA microarray assay and reverse transcription
      polymerase chain reaction (RT-PCR) analysis showed that the gene expression of
      the alpha-2,6-sialyltransferase I (ST6Gal I), which transfers sialic acid to
      galactose residues of N-glycans, decreases in the aged cells. These results
      indicate that the concordant decrease of the alpha-2,6-sialylation of N-glycans
      with the ST6Gal I gene expression is induced in TIG-3 cells by in vitro aging.

PMID- 16897186
TI  - Ectopic expression of N-acetylglucosamine 6-O-sulfotransferase 2 in chemotherapy
      resistant ovarian adenocarcinomas.
AB  - Mucinous and clear cell adenocarcinomas are the major histological types of
      ovarian epithelial cancer and are associated with a poor prognosis due to their
      resistance to chemotherapy. A novel tumor marker specific for ovarian mucinous
      and clear cell adenocarcinomas would be helpful for overcoming these serious
      diseases. We showed previously by enzymological characterization and RT-PCR that
      colonic mucinous adenocarcinoma tissues ectopically express GlcNAc6ST-2, a member
      of the carbohydrate 6-O-sulfotransferase family (Seko, A. et al. (2002)
      Glycobiology 12, 379-388). Here, we prepared a GlcNAc6ST-2-specific polyclonal
      antibody for immunohistochemical analysis and found that GlcNAc6ST-2 is
      ectopically expressed by not only colonic mucinous adenocarcinomas but also
      ovarian mucinous, clear cell and papillary serous adenocarcinomas. In contrast,
      solid serous adenocarcinomas, endometrioid adenocarcinomas, and mucinous adenomas
      expressed GlcNAc6ST-2 much less frequently or not at all. RT-PCR analysis
      confirmed that GlcNAc6ST-2 transcripts are expressed in ovarian mucinous
      adenocarcinomas but not in mucinous adenomas. In addition, immunohistochemical
      analysis using sulfated glycan-specific monoclonal antibodies showed that ovarian
      adenocarcinoma cells express GlcNAc 6-O-sulfated glycans, including an L-selectin
      ligand and its related glycans. These results indicate that GlcNAc6ST-2 would be
      a novel tumor antigen that is specifically expressed in ovarian mucinous, clear
      cell and papillary serous adenocarcinomas.

PMID- 16897187
TI  - The potential role of DFNA5, a hearing impairment gene, in p53-mediated cellular
      response to DNA damage.
AB  - The tumor suppressor p53 plays a crucial role in the cellular response to DNA
      damage by transcriptional activation of numerous downstream genes. Although a
      considerable number of p53 target genes have been reported, the precise mechanism
      of p53-regulated tumor suppression still remains to be elucidated. Here, we
      report a novel role of the DFNA5 gene in p53-mediated etoposide-induced cell
      death. The DFNA5 gene has been previously reported to be responsible for
      autosomal-dominant, nonsyndromic hearing impairment. The expression of the DFNA5
      gene was strongly induced by exogenous and endogenous p53. The chromatin
      immunoprecipitation assay indicated that a potential p53-binding sequence is
      located in intron 1 of the DFNA5 gene. Furthermore, the reporter gene assay
      revealed that the sequence displays p53-dependent transcriptional activity. The
      ectopic expression of DFNA5 enhanced etoposide-induced cell death in the presence
      of p53; however, it was inhibited in the absence of p53. Finally, the expression
      of DFNA5 mRNA was remarkably induced by gamma-ray irradiation in the colon of
      p53(+/+) mice but not in that of p53(-/-) mice. These results suggest that DFNA5
      plays a role in the p53-regulated cellular response to genotoxic stress probably
      by cooperating with p53.

PMID- 16897189
TI  - Refinement of the locus for autosomal recessive cone-rod dystrophy (CORD8) linked
      to chromosome 1q23-q24 in a Pakistani family and exclusion of candidate genes.
AB  - Cone-rod retinal dystrophy (CORD) characteristically leads to early impairment of
      vision due to the simultaneous involvement of both cone and rod photoreceptor
      cells. Several loci/genes have been identified for CORD, including the cone-rod
      dystrophy (CORD8) locus [OMIM#605549] identified for a Pakistani family. All
      members of this family underwent detailed clinical re-examination to determine
      the nature of the dystrophy. All affected individuals suffered from bilateral
      CORD8 with an autosomal recessive mode of inheritance. The CORD8 locus, mapped on
      chromosome 1q12-q24, consisted of a very large critical disease region of 21 cM.
      Analysis with more recently available microsatellite markers within the reported
      region showed heterozygosity with some of the new markers, and the crossovers
      lead to a refinement of the disease region from 21 to 11.53 cM. Mutation
      screening has excluded some of the candidate genes in the region. The disease
      phenotype of this family could be due to a mutation in a novel gene located
      within the refined CORD8 locus.

PMID- 16897188
TI  - Frequent DAP kinase but not p14 or Apaf-1 hypermethylation in B-cell chronic
      lymphocytic leukemia.
AB  - Dysregulation of apoptosis, and thus the p14/DAP kinase/HDM2/p53/Apaf-1 pathway,
      is potentially important in carcinogenesis. Chronic lymphocytic leukemia (CLL),
      uncommon in the Chinese, is a disease characterized by impaired apoptosis, of the
      neoplastic lymphocytes. Hypermethylation of p14, DAP kinase and Apaf-1 was
      studied by methylation-specific polymerase chain reaction (MSP) with primers for
      methylated (M-MSP) and unmethylated (U-MSP) alleles in 50 diagnostic marrow
      samples from patients with CLL. Chinese CLL patients had an indolent course
      similar to Caucasians with median overall survival (OS) of 96 months, which was
      adversely affected by advanced Rai stage (projected 5-year OS = 72% and 39% for
      Rai < or = 2 and Rai > 2; P = 0.01). DAP kinase was methylated in 18 (36%)
      patients while p14 and Apaf-1 were completely unmethylated in all the primary CLL
      samples. There was no correlation between DAP kinase hypermethylation and age,
      sex, poor-risk karyotype, lymphocyte count and Rai stage at diagnosis. Projected
      OS for patients with and without DAP kinase hypermethylation were 59 and 57% (P =
      0.91). DAP kinase, but not p14 and Apaf-1, of the DAP kinase/p14/HDM2/p53/Apaf-1
      pathway is frequently hypermethylated in CLL, but not of prognostic significance.
      Moreover Chinese patients with CLL share a similarly indolent clinical course,
      and this is the first comprehensive study on p14, DAP kinase and Apaf-1
      hypermethylation in CLL.

PMID- 16897190
TI  - Functional analysis of PKHD1 splicing in autosomal recessive polycystic kidney
      disease.
AB  - Autosomal recessive polycystic kidney disease (ARPKD) is caused by mutations in
      the PKHD1 (polycystic kidney and hepatic disease 1) gene on chromosome 6p12. The
      longest continuous open reading frame comprises 66 exons encoding a novel 4,074
      aa multidomain integral membrane protein (polyductin/fibrocystin) of unknown
      function. Various alternatively spliced transcripts may additionally result in
      different isoproteins. Overall, the large size of PKHD1, its complex pattern of
      splicing, multiple allelism and lack of knowledge of the encoded
      protein's/proteins' functions pose significant challenges to DNA-based diagnostic
      testing. Nucleotide substitutions, particularly if residing in regulatory
      elements or introns outside the splice consensus sites, are often difficult to
      assess without further functional analyses and cannot be unambiguously classified
      as disease-associated. Investigations on the transcript level, however, are
      hampered as PKHD1 is not widely expressed in blood lymphocytes. We thus
      determined the functional significance of the novel splice site mutation c.53
      3C>A in intron 2 by RNA analyses by minigene-construction. The mutant allele was
      shown to cause skipping of exon 3. Thus, given the minigene results together with
      400 control chromosomes negative for this change, segregation of the mutation
      with the phenotype, and a significant lowering of the strength of the splice site
      by bioinformatics, the mutant allele is most likely pathogenic. To the best of
      our knowledge, this is the first study that defines the consequences of a PKHD1
      splice mutation and underlines the relevance of functional analyses in
      determining the pathogenicity of changes of unknown significance.

PMID- 16897191
TI  - Polymorphisms in interleukin 8 and its receptors (IL8, IL8RA and IL8RB) and
      association of common IL8 receptor variants with peripheral blood eosinophil
      counts.
AB  - Airway inflammation is a major factor in the pathogenesis of asthma. Interleukin
      8 (IL8) is a potent proinflammatory cytokine that interacts with its receptors,
      IL8RA and IL8RB. We investigated the genetic polymorphisms in IL8, IL8RA, and
      IL8RB for any association with risk of asthma and peripheral blood eosinophil
      counts in a Korean population. By carrying out direct sequencing in 24
      individuals, we identified 20 sequence variants within exons and their flanking
      regions, including the 1.5 kb promoter regions of IL8, IL8RA, and IL8RB. Among
      them, seven common single-nucleotide polymorphisms (SNPs) were selected for
      genotyping in our asthma cohort (n = 1,439). Two common haplotypes in IL8 and
      three in IL8RA and IL8RB (defined as one block) were identified. Although none of
      the polymorphisms showed a significant association with risk of asthma, IL8RA-B
      ht2 showed a significant association with the peripheral blood eosinophil counts
      (%) among asthma patients, e.g., lower eosinophil levels among individuals with
      the homozygous IL8RA-B ht2 (3.55 +/- 3.39%) than among other asthmatic patients
      (5.52 +/- 5.55%; P (corr) = 0.018). Our findings suggest that polymorphisms and
      haplotypes in IL8RA and IL8RB might be among the genetic factors underlying
      production of peripheral blood eosinophil.

PMID- 16897192
TI  - Longevity-associated NADH dehydrogenase subunit-2 237 Leu/Met polymorphism
      influences the effects of alcohol consumption on serum uric acid levels in
      nonobese Japanese men.
AB  - NADH dehydrogenase subunit-2 237 leucine/methionine (ND2-237 Leu/Met)
      polymorphism is reportedly associated with longevity in the Japanese population.
      The ND2-237Met genotype may confer resistance to cardiovascular and
      cerebrovascular atherogenic diseases. Hyperuricemia is one of the risk factors
      for cardiovascular disease. To investigate whether ND2-237 Leu/Met polymorphism
      is associated with serum uric acid (SUA) levels, we conducted a cross-sectional
      study in 321 healthy Japanese male subjects. In nonobese (body mass index,
      BMI<25) male subjects, interaction between ND2-237 Leu/Met genotypes and drinking
      frequency on SUA levels was observed (P=0.031). The SUA levels were significantly
      higher in daily drinkers with ND2-237Leu than in non-daily drinkers with ND2
      237Leu (P=0.018). In nonobese men, after adjustment for covariates, daily
      drinkers with ND2-237Leu had a significantly higher odds ratio (OR) for
      hyperuricemia (SUA> or =6.5 mg/dl: vs. daily drinkers with ND2-237Met, OR=3.26,
      95% confidence interval (CI) 1.14-9.29; vs. non-daily drinkers with ND2-237Leu,
      OR=3.22, 95% CI 1.39-7.45; SUA> or =7.0 mg/dl: vs. non-daily drinkers with ND2
      237Met, OR=3.53, 95% CI 1.00-12.4). However, in obese (BMI> or =25) men, no
      significant interaction between ND2-237 Leu/Met polymorphism and habitual
      drinking on SUA levels or on the risk for hyperuricemia was observed. These
      results suggest that ND2-237 Leu/Met polymorphism modulates the effects of daily
      alcohol consumption on SUA levels in nonobese Japanese men.

PMID- 16897193
TI  - The influence of snowfall, temperature and social relationships on sleeping
      clusters of Japanese monkeys during winter in Shiga Heights.
AB  - We studied Japanese monkeys (Macaca fuscata) of the Shiga A(1) troop at their
      sleeping sites in Shiga Heights, Japan, for 41 nights during 3 winters. Monkeys
      chose their sleeping sites in Japanese cedars and in deciduous broad-leaved
      forests on non-snowing nights and in Japanese cedar forests on snowing nights. We
      counted 399 sleeping clusters in which 2 or more monkeys remained in physical
      contact through the night and 43 solitary sleeping monkeys, though monkeys did
      not maintain physical contact with others in the daytime. We found 397 clusters
      on tree branches and 2 clusters on rocks. The mean size of huddling clusters was
      3.06+/-1.22 SD. The cluster size (3.17+/-1.26 SD) at lower ambient temperatures
      between -7 and -4 degrees C was larger than that at higher temperatures between 
      2 and 4 degrees C (cluster size 2.88+/-1.13 SD). Most clusters were composed of
      kin. Females kept close to related females in the daytime and huddled with them
      at night. The highest-ranking male mainly huddled with his kin and his familiar
      females. Other males kept farther apart from each other in the daytime, probably
      to avoid social conflicts. Through cold winter nights, however, such males
      reduced inter-individual distances and huddled with other males. Japanese monkeys
      appear to recognize three types of inter-individual distances: an intimate
      distance less than 1 m, a personal distance of 1-3 m and a social distance of 3
      20 m; they change their inter-individual distances according to social and
      ecological circumstances.

PMID- 16897194
TI  - Leaf-swallowing in Nigerian chimpanzees: evidence for assumed self-medication.
AB  - A field study in Gashaka, Nigeria, adds the fourth subspecies of chimpanzee, Pan
      troglodytes vellerosus, to the list of African ape populations in which leaf
      swallowing occurs. Unchewed herbaceous leaves of Desmodium gangeticum
      (Leguminosae-Papilionoideae) were recovered in 4% of 299 faecal samples of wild
      chimpanzees and clumps of sharp-edged grass leaves in 2%. The ingestion is
      believed to serve self-medicatory purposes because the leaves had a rough surface
      or were sharp-edged (which could be related to parasite control through a self
      induced increase of gut motility), were not chewed, were excreted whole
      (indicating that they were not ingested for nutritional purposes), leaf
      swallowing was restricted to the rainy season (during which time parasite re
      infections are more common), and parasitic worms (Oesophagostomum stephanostomum)
      were found together with the leaves.

PMID- 16897195
TI  - Multicenter study for Legg-Calve-Perthes disease in Japan.
AB  - BACKGROUND: The Japanese Pediatric Orthopaedic Association created a project team
      in 2000 to research pediatric orthopedic disease through a multicenter study. The
      aim of this study was to collect epidemiological data on Legg-Calve-Perthes
      disease (LCPD) in Japan. METHODS: The following data were collected by a survey:
      age, sex, date of diagnosis, family history, sports history, affected sites,
      symptoms, location of pain, Catterall classification, Herring classification,
      date of treatment initiation, treatment methods, bracing period, and Stulberg
      classification. RESULTS: A total of 711 patients with 766 affected hips were seen
      from January 1, 1993 to December 31, 1995. The average annual incidence of LCPD
      was 0.9/100 000. The average age at diagnosis was 7 years 1 month (2.3-14.3
      years). The male/female ratio of the study population was 6.3 : 1.0. The affected
      side ratio (right hip/left hip/both hips) was 5.1 : 6.8 : 1.0. Both hips were
      affected in 7.7% of this series. By the Stulberg classification there were 211
      (69.4%) type I and II patients (of 304 total patients). Six treatment methods for
      unilateral LCPD were compared, and there were no significant differences in
      outcome among the six groups. The ordinal logistic regression analysis showed
      that the Herring classification, age at the time of diagnosis, and the affected
      side (for unilateral LCPD) were significant predictors. The ordinal logistic
      regression analysis also showed that operative treatment had a better outcome
      than conservative treatment, with an odds ratio of 1.872. CONCLUSIONS: Many
      containment methods for LCPD have been performed in Japan, and the optimal
      treatment method for LCPD was not determined in this study. The overall outcome,
      however, was not worse than that in worldwide reports.

PMID- 16897196
TI  - A simple method to determine the pelvic inclination angle based on
      anteroposterior radiographs.
AB  - BACKGROUND: The aim of this study was to propose a simple method to determine the
      pelvic inclination angle using anteroposterior radiographs of the hip. METHODS:
      The 283 subjects were randomly selected from patients who had undergone hip
      surgery at our institution from July 2002 to June 2004. Anteroposterior (AP) and
      lateral radiographs of the pelvis were obtained in the standing position. To
      assess the pelvic inclination angle from AP radiographs, a formula was determined
      by a trigonometric function. A significant correlation between the angle
      calculated by the formula and the measured angle (theta(0)) on lateral
      radiographs was confirmed. The calculated angle (theta(1)) was obtained from two
      measured values: the pelvic foramen height (H) on AP radiographs and the pelvic
      foramen distance (D) on lateral radiographs. The formula used was as follows: sin
      theta = H/D. The calculated angle (theta(2)) was obtained from one measured value
      -the pelvic foramen height on AP radiographs--because the pelvic foramen distance
      on lateral radiographs substituted for the average of the pelvic foramen distance
      investigated in 236 patients. The formula was sin theta = H/average. RESULTS: The
      correlation between the calculated angle (theta(1)) and the measured angle
      (theta(0)) was significant, and the correlation between calculated angle theta(1)
      and calculated angle theta(2) was also significant. CONCLUSIONS: The pelvic
      inclination angle can be estimated by measuring the height of the pelvic foramen
      according to our formula. Our formula was shown to have adequate reliability and
      reproducibility.

PMID- 16897197
TI  - Relation between atlantoaxial (C1/2) and cervical alignment (C2-C7) angles with
      Magerl and Brooks techniques for atlantoaxial subluxation in rheumatoid
      arthritis.
AB  - BACKGROUND: A few studies have reported the relation between the atlantoaxial
      (C1/2) angle and cervical alignment (C2-C7) angle after a Magerl and Brooks (M&B)
      surgical procedure to treat atlantoaxial subluxation (AAS) in patients with
      rheumatoid arthritis (RA). However, no study has examined an optimum preoperative
      C1/2 angle reduction. We aimed to assess the relation between the C1/2 angle
      reduction and the C2-C7 angle change in patients with progressive RA who
      underwent the M&B procedure. METHODS: We retrospectively analyzed the relation
      between the preoperative C1/2 angle and C2-C7 angle in 28 consecutive RA patients
      using their clinical and radiological data. Differences in the preoperative and
      postoperative C1/2 and C2-C7 angles were detected. Correlations of these angles
      and the reduced degree of angles were examined. The Ranawat grading scale and
      Japanese Orthopaedic Association (JOA) scores were used to determine myelopathy.
      Pain was categorized into five categories according to severity. Clinical and X
      ray evaluations were collected before surgery, at 3 and/or 6 months after
      surgery, and at final follow-up. RESULTS: Clinical symptoms, Ranawat grade, and
      JOA scores improved postoperatively, and patients achieved bony union within 3
      months. We observed a strong and significant correlation between the reduced C1/2
      angle and the change in the C2-C7 angle. Patients with a preoperative C1/2 angle
      of <20 degrees had markedly reduced cervical lordotic angle but this condition
      was not seen in patients with a preoperative C1/2 angle of >or=20 degrees . The
      optimum C1/2 angle was estimated as [20 degrees - (preoperative C1/2 angle)] in
      patients with a C1/2 angle <20 degrees or as an in situ angle in patients with a
      C1/2 angle of >or=20 degrees . CONCLUSIONS: Surgeons performing the M&B procedure
      need to select patients carefully and avoid complete or overreduction of the C1/2
      angle to prevent serious postoperative SAS and myelopathy.

PMID- 16897198
TI  - Increasing postural sway in rural-community-dwelling elderly persons with knee
      osteoarthritis.
AB  - BACKGROUND: The purpose of this study was to clarify the influence of pain and
      radiographic findings of osteoarthritis (OA) of the knee on postural stability in
      rural-community-dwelling elderly persons. METHODS: A total of 314 participants,
      consisting of 98 men and 216 women, aged 55 to 83 years, were investigated.
      Subjects were classified into four groups according to the symptoms and
      radiographic findings: Normal; Pain (pain without radiographic OA); Asymptomatic
      OA (radiographic OA without pain); Symptomatic OA (pain with radiographic OA).
      Knee pain was defined as unilateral or bilateral pain of the knee that had
      persisted for more than 1 month. Radiographic OA was defined as grades 2-4
      according to the Kellgren and Lawrence criteria. The movement of the center of
      pressure (COP) was measured using a force platform to quantify postural sway.
      RESULTS: Among the men, subjects in the Asymptomatic and Symptomatic OA groups
      showed higher values of the envelopment area tracing by the movement of the COP
      (E AREA) and the distance of the movement of the COP per second (LNG/TIME) under
      closed-eyes condition. Among the women, subjects in the Asymptomatic and
      Symptomatic OA groups showed higher values of E AREA and LNG/TIME under both open
      and closed-eyes conditions. In the regression models consisting of the variables
      pain and radiographic OA, all estimates for pain were less than zero in both
      sexes. The value was significant only on the E AREA under closed-eyes conditions
      in women. On the other hand, all estimates for radiographic OA were higher than
      zero for both sexes. These values were significant for E AREA and LNG/TIME under
      open-eyes conditions in women, and E AREA and LNG/TIME under closed-eyes
      conditions in both sexes. CONCLUSIONS: Subjects with OA showed greater postural
      sway than those without it. Only radiographic OA was a significant factor for
      increasing postural sway.

PMID- 16897199
TI  - Preparing a version of the Nottingham Adjustment Scale (for psychological
      adjustment) tailored to osteoarthritis of the hip.
AB  - BACKGROUND: The Nottingham Adjustment Scale-Japanese version (hereinafter
      referred to as NAS-J) was developed to measure psychological adaptation to
      visually impairment. Several disease-specific modified versions have been
      developed in Japan. The purpose of this study was to develop and test the
      reliability, validity, and responsiveness of the NAS-J for hip osteoarthritis
      patients. METHODS: Patients with osteoarthritis of the hip managed as outpatients
      at the Department of Orthopaedic Surgery of one university hospital gave informed
      written consent to be enrolled in this study. Subjects were asked to complete a
      questionnaire consisting of the NAS-J--Hip edition (hereinafter referred to as
      NAS-J-HIP), health-related QOL (Short Form 36). Subjects' medical and treatment
      histories, and the Japanese Hip Society's Evaluation Chart of Hip Joint Functions
      (hereinafter referred to as the JOA score) were also collected from their medical
      records. Psychometric analyses were conducted to test reliability, validity, and
      responsiveness. RESULTS: A total of 231 patients agreed to participate in the
      survey, and responses were obtained from 168 (72.7%). Their mean +/- SD age was
      52.5 +/- 12.4 years, and the mean JOA score was 80.9 points. By factor analysis
      using the principal factor method, seven factors were extracted: (1)
      anxiety/depression, (2) self-esteem, (3) attitude, (4) locus of control, (5)
      acceptance, (6) self-efficacy, and (7) attributional style. Concurrent validity
      was the result according to the near hypothesis. Cronbach's alpha-coefficient
      ranged from 0.68 to 0.83, indicating high internal consistency. CONCLUSIONS: For
      hip osteoarthritis patients, construct validity was confirmed for NAS-J-HIP.
      Furthermore, seven factors comprising 27 items with high internal consistency
      were incorporated into NAS-J-HIP. This scale can be used to assess the
      psychological adaptation of hip osteoarthritis patients.

PMID- 16897200
TI  - Epidural neuroplasty versus physiotherapy to relieve pain in patients with
      sciatica: a prospective randomized blinded clinical trial.
AB  - BACKGROUND: Epidural neuroplasty seems to be one of the promising minimally
      invasive techniques for adhesiolysis in patients with chronic sciatica with or
      without low back pain. However, because no data exist from randomized studies the
      aim was to investigate whether this procedure is superior to conservative
      treatment with physiotherapy. METHODS: A total of 99 patients with chronic low
      back pain were enrolled in this study and randomly assigned into either a group
      with physiotherapy (n = 52) or a second group undergoing epidural neuroplasty (n
      = 47). Patients were assessed before and 3, 6, and 12 months after treatment by a
      blinded investigator. RESULTS: After 3 months, the visual analog scale (VAS)
      score for back and leg pain was significantly reduced in the epidural neuroplasty
      group, and the need for pain medication was reduced in both groups. Furthermore,
      the VAS for back and leg pain as well as the Oswestry disability score were
      significantly reduced until 12 months after the procedure in contrast to the
      group that received conservative treatment. CONCLUSIONS: Epidural neuroplasty
      results in significant alleviation of pain and functional disability in patients
      with chronic low back pain and sciatica based on disc protrusion/prolapse or
      failed back surgery on a short-term basis as well as at 12 months of follow-up.

PMID- 16897201
TI  - Interleukin-1, interleukin-6, and interleukin-10 responses after antibiotic
      treatment in experimental chronic Staphylococcus aureus osteomyelitis.
AB  - BACKGROUND: Staphylococcal implant infections' response to treatment may be
      correlated with cytokine production. We investigated the effect of certain
      antibiotics on the cytokine response in experimental osteomyelitis. METHODS: A
      stainless steel needle with an adherent slime-producing Staphylococcus aureus was
      implanted intramedullarly in the left tibia of 40 adult male Wistar rats. At 42
      days after implantation, cefuroxime, vancomycin, tobramycin, and ciprofloxacin
      were administered intramuscularly every 12 h for 21 days. The control group was
      given no antibiotic. At the end of the treatment, implants and tibias were
      retrieved, and the bacterial numbers were estimated. Cytokines [interleukin
      1alpha (IL-1alpha), IL-6, and IL-10] were determined (ELISA) in the tibial
      extract. RESULTS: Vancomycin and cefuroxime inhibited bone colonization in all
      tibias, and tobramycin and ciprofloxacin inhibited it only partially. Cefuroxime
      reduced the number of bacteria that adhered to the implants more than the other
      antibiotics. IL-1alpha and IL-6 showed higher levels in the ciprofloxacin-treated
      group than in the cefuroxime-treated and control groups. IL-6 levels in rats
      treated with cefuroxime were lower than in rats treated with tobramycin or
      vancomycin and the control group. Cefuroxime decreased IL-10 levels more than
      ciprofloxacin or vancomycin or those seen in the control group. CONCLUSIONS: The
      cefuroxime group showed the greatest decrease of pro-inflammatory cytokines.
      Different antibiotics produce different cytokine reactions that should be studied
      to choose the best treatment.

PMID- 16897202
TI  - Use of glycyrrhizin in prevention of tissue damage caused by ischemia-reperfusion
      in rabbit hind limbs.
AB  - BACKGROUND: Glycyrrhizin, an agent that can bind to selectins and inhibit their
      ability to bind neutrophils, was found to be effective in preventing tissue edema
      caused by ischemia-reperfusion in a rabbit model. METHODS: Complete ischemia was
      produced by applying a tight Esmarch tourniquet to the hind limbs of 24 Japanese
      white rabbits. Immediately before and 1 h after release of the tourniquet, 12
      animals were given glycyrrhizin intravenously; 12 controls received saline.
      RESULTS: The mean relative increase in the circumference of the shins before and
      after ischemia-reperfusion with or without glycyrrhizin treatment was 4.6% +/-
      2.4% and 9.6% +/- 4.2%, respectively, indicating that tissue edema caused by the
      ischemia-reperfusion was significantly attenuated by glycyrrhizin. Histological
      studies of cross sections of the anterior tibial muscle 24 h after reperfusion
      showed a significant reduction in the incidence of necrotic muscle fibers in the
      glycyrrhizin-treated animals compared with the controls that did not receive
      glycyrrhizin. The mRNA levels of P- and E-selectin 24 h after reperfusion were
      significantly higher in the ischemic anterior tibial muscle than in the
      nonischemic normal muscle. After 24 h of reperfusion, the mean activity of
      myeloperoxidase, a neutrophil-specific enzyme, in the anterior tibial muscles of
      the group given glycyrrhizin (0.0022 +/- 0.0013 absorbance units) was lower than
      that of the untreated group (0.027 +/- 0.026 absorbance units). CONCLUSIONS:
      These data suggest that glycyrrhizin treatment is effective in suppressing the
      acute inflammatory reaction or edema following ischemia-reperfusion and might be
      potentially useful in clinical practice for preventing ischemia-reperfusion
      injuries to the extremities.

PMID- 16897204
TI  - Treatment of knee osteoarthritis associated with extraarticular varus deformity
      of the femur: staged total knee arthroplasty following corrective osteotomy.

PMID- 16897203
TI  - Biomechanical and immunohistochemical analysis of high hydrostatic pressure
      treated Achilles tendons.
AB  - BACKGROUND: Reconstruction of bone defects caused by malignant tumors is carried
      out in different ways. At present, tumor-bearing bone segments are devitalized
      mainly by extracorporeal irradiation or autoclaving, but both methods have
      substantial disadvantages. In this regard, high hydrostatic pressure (HHP)
      treatment of the bone is a new, advancing technology that has been used in
      preclinical testing to inactivate normal cells and tumor cells without altering
      the biomechanical properties of the bone. The aim of this study was to examine
      the biomechanical and immunohistochemical properties of tendons after exposure to
      HHP and to evaluate whether preservation of the bony attachment of tendons and
      ligaments is possible. METHODS: For this, 19 paired Achilles tendons were
      harvested from both hindlimbs of 4-month-old pigs. After preparation, the cross
      sectional area of each tendon was determined by magnetic resonance imaging (MRI).
      For each animal, one of the two tendons was taken at random and exposed to a
      pressure of 300 MPa (n = 9) or 600 MPa (n = 10). RESULTS: The contralateral
      tendon served as an untreated control. The biomechanical properties of the
      tendons remained unchanged with respect to the tested parameters: Young's modulus
      (MPa) and tensile strength (MPa). This finding is in line with
      immunohistochemical labeling results, as no difference in the labeling pattern of
      collagen I and versican was observed when comparing the HHP group (at 600 MPa) to
      the untreated control group. CONCLUSIONS: We anticipate that during orthopedic
      surgery HHP can serve as a novel, promising methodical approach to inactivate
      Achilles tendon and bone cells without altering the biomechanical properties of
      the tendons. This should allow one to preserve the attachment of tendon and
      ligaments to the devitalized bone and to facilitate functional reconstruction.

PMID- 16897205
TI  - Distraction osteogenesis of a fresh fracture site using an external fixator.

PMID- 16897206
TI  - Functional evaluation of four patients treated with V-Y quadricepsplasty in total
      knee arthroplasty.

PMID- 16897207
TI  - Salvage surgery for persistent femoral nonunion after total knee arthroplasty
      using a megaprosthesis.

PMID- 16897208
TI  - Sudden onset of saphenous neuropathy associated with hereditary multiple
      exostoses.

PMID- 16897209
TI  - Purple glove syndrome associated with intravenous phenytoin administration in a
      patient with severe mental and motor retardation.

PMID- 16897211
TI  - Scaphoid fractures and nonunions: diagnosis and treatment.
AB  - BACKGROUND: Scaphoid fractures are commonly seen in orthopedic practice. An
      organized and thoughtful approach to diagnosis and treatment can facilitate good
      outcomes. However, despite optimal treatment, complications may ensue. In the
      setting of nonunion or an avascular proximal pole, vascularized bone grafting may
      be needed. METHODS AND RESULTS: In this article we review the literature
      regarding these injuries and describe an approach to diagnosis, treatment, and
      management of scaphoid fractures and nonunions. CONCLUSION: Scaphoid fractures
      and nonunions may present as challenging problems in practice, but a systematic
      and deliberate approach can facilitate optimal results.

PMID- 16897210
TI  - Premalignant conditions of bone.

PMID- 16897213
TI  - Treatment of eyelid epithelial neoplasm by targeting sonic hedgehog signaling: an
      experimental study.
AB  - PURPOSE: To evaluate the effect of cyclopamine, an inhibitor of the Sonic
      hedgehog (Shh) signal, on the growth of an epithelial neoplasm. METHODS:
      Chemically induced eyelid tumors in XPC-null mice (n=40) were treated daily with
      a subcutaneous injection of cyclopamine (1 mg/animal) for 7 days. The animals
      were killed after bromodeoxyuridine (BrdU) labeling, and the tumors were
      histologically examined. An in vitro study was conducted by using a squamous cell
      carcinoma (SCC) cell line. The SCC cells were treated with 0, 12.5, or 25.0
      microg/ml recombinant Shh (rShh) and either 0 or 100 microM cyclopamine, and cell
      proliferation was evaluated by using an MTT assay. Cells from this cell line were
      also implanted subcutaneously in nude mice (n=8) to develop tumors, and the
      effect of cyclopamine administration was examined in the developed tumors.
      RESULTS: Histology showed that cyclopamine treatment suppressed BrdU
      incorporation and induced apoptosis in the majority of cells in tumors chemically
      induced in the eyelid of the XPC-null mice. Cell proliferation of the SCC cell
      line was enhanced by adding rShh, and this effect was abolished by adding
      cyclopamine. Proliferation of the SCC cell line was not affected by adding
      cyclopamine in the absence of rShh. On the other hand, the SCC cells expressed
      Shh in vivo in tumors developed in nude mice, but cyclopamine suppressed cell
      proliferation in the tumors, and the Shh-signaling pathway was inhibited by
      cyclopamine-induced apoptosis. CONCLUSIONS: Cyclopamine inhibits proliferation
      and induces apoptosis in epithelial tumor cells in vivo. The Shh-signaling
      pathway may be a potential therapeutic target for patients with eyelid tumors.

PMID- 16897214
TI  - Correlation between higher blood flow velocity in the central retinal vein than
      in the central retinal artery and severity of nonproliferative diabetic
      retinopathy.
AB  - PURPOSE: To assess the correlation between a higher blood flow velocity in the
      central retinal vein (CRV) than in the central retinal artery (CRA) and the
      severity of nonproliferative diabetic retinopathy (non-PDR). METHODS: We
      evaluated both eyes of 20 non-PDR patients with higher peak systolic velocity
      (PSV) in the CRV than in the CRA unilaterally as determined by color Doppler
      imaging (CDI). The eyes with higher PSV in the CRV were placed in group D2-H, and
      the fellow eyes were placed in group D2-L. The stage of non-PDR was determined by
      the guidelines of the Early Treatment Diabetic Retinopathy Study. Normal subjects
      and non-PDR patients without higher PSV in the CRV were evaluated as CDI
      controls. RESULTS: Advanced non-PDR (P=0.001) and cystoid macular edema (P=0.02)
      were statistically more frequent in group D2-H. The velocities in the ophthalmic
      artery and the short posterior ciliary artery were not statistically different
      among all groups. The velocities in the CRA were similar in all non-PDR groups
      and significantly lower than in the normal subjects (P<0.05). The velocities in
      the CRV were significantly higher only in group D2-H (P<0.001). CONCLUSION:
      Higher PSV in the CRV than in the CRA was significantly correlated with the
      severity of non-PDR, especially in the presence of cystoid macular edema.

PMID- 16897215
TI  - Effects of reference axes used during measurements of ocular and corneal higher
      order aberrations in patients following LASIK.
AB  - PURPOSE: To determine the effects of the reference axes used during the
      measurements of ocular and corneal higher-order aberrations (HOAs) in patients
      before and after laser in situ keratomileusis (LASIK). METHODS: Wavefront sensing
      and corneal topography were determined for 29 eyes of 15 patients before and
      after LASIK. Ocular and corneal HOAs were calculated for 4-mm- and 6-mm-diameter
      pupils with the instrument aligned with the line of sight (LOS) or with the
      vertex normal (VN). RESULTS: For ocular HOAs after surgery, the spherical-like
      aberration was significantly larger when the VN axis rather than the LOS axis was
      used for pupils of both diameters. For corneal HOAs before surgery, in addition
      to the larger spherical-like aberration for VN, coma-like aberrations were
      significantly larger with LOS than with VN for both pupil diameters. For corneal
      HOAs after surgery, the spherical-like aberrations and total HOAs for 4-mm
      diameter pupils with VN were significantly larger than those with LOS.
      CONCLUSIONS: The HOAs were significantly different depending on the axes used and
      should be described on the basis of a common axis. These results suggest that the
      anterior surface of the normal or post-LASIK cornea is more rotationally
      symmetrical along the VN than along the LOS.

PMID- 16897216
TI  - Intensity analysis of Hartmann-Shack images in cataractous, keratoconic, and
      normal eyes to investigate light scattering.
AB  - PURPOSE: A clinical investigation of novel methods for evaluating light
      scattering using a Hartmann-Shack aberrometer. METHODS: Aberrometry was performed
      on normal eyes (n=7; patient age, 26.7+/-2.5 years, mean+/-SD), eyes with
      keratoconus (n=22; patient age, 26.1+/-8.1 years), and eyes with cataract (n=17;
      patient age, 56.5+/-16.9 years) using a Hartmann-Shack wavefront aberrometer. We
      introduced two methods: (1) a contrast method, in which we calculated the inverse
      of contrast of the local images around 12 spots in a Hartmann-Shack image, and
      (2) a difference of point spread function (PSF) method, in which we analyzed the
      difference between the width of the PSF computed with aberration information and
      the width of the measured PSF, which contains both aberration and light
      scattering information. RESULTS: The inverse contrast in cataractous eyes (5.04+/
      3.06 inverse contrast units) was significantly larger than that in normal eyes
      (1.57+/-0.56) or keratoconic eyes (1.83+/-0.79). The difference of PSF in
      cataractous eyes (81.8+/-65.2 microm) was also significantly larger than that in
      normal eyes (9.3+/-4.3 microm) or keratoconic eyes (30.0+/-20.1 microm). The
      inverse contrast and the difference in the PSF were highly correlated (r=0.89,
      P<0.0001). CONCLUSIONS: The two methods introduced here successfully
      distinguished cataractous eyes from normal and keratoconic eyes. After the
      results were analyzed by a discriminant analysis, the separation of the three
      categories proved to be excellent.

PMID- 16897218
TI  - Comparison of fornix- and limbus-based conjunctival flaps in mitomycin C
      trabeculectomy with laser suture lysis in Japanese glaucoma patients.
AB  - PURPOSE: To analyze the results of mitomycin C (MMC) trabeculectomy and laser
      suture lysis using either fornix-based (FB) or limbus-based (LB) conjunctival
      flaps. METHODS: Eighty-two Japanese glaucoma patients were treated by MMC
      trabeculectomy, with 38 eyes receiving an FB conjunctival flap and 44 eyes
      receiving an LB conjunctival flap. Postoperative intraocular pressure (IOP), the
      probability of success, and complications were compared between the FB and LB
      groups. RESULTS: The IOP of the FB group decreased from 21.6+/-7.90 mmHg to
      9.75+/-3.23 mmHg at 12 months postoperation, and the IOP of the LB group
      decreased from 21.3+/-6.77 mmHg to 9.30+/-3.16 mmHg. The postoperative IOPs were
      similar in the two groups at all postoperative time points. A life-table analysis
      (Kaplan-Meier method) showed that the survival rate was similar in the two groups
      but tended to be lower in the early postoperative period in the FB group.
      Complications were similar also, with the exception of increased leakage in the
      FB group. CONCLUSIONS: MMC trabeculectomy results were similar between FB and LB
      conjunctival flaps, in agreement with previous reports. However, increased care
      may be warranted when an FB flap is used in MMC trabeculectomy.

PMID- 16897217
TI  - Additional reduction in intraocular pressure achieved with latanoprost in normal
      tension glaucoma patients previously treated with unoprostone.
AB  - PURPOSE: To determine whether treatment with latanoprost eye drops is able to
      further reduce intraocular pressure (IOP) in normal-tension glaucoma (NTG)
      patients whose IOP has been well controlled with unoprostone. PATIENTS AND
      METHODS: A total of 34 eyes (34 individuals) with NTG that had been treated with
      0.12% unoprostone eye drops twice daily for >or=3 months were switched to
      treatment once daily with eye drops containing 0.005% latanoprost. IOP was
      measured before and 1, 2, and 3 months after the switch to latanoprost. RESULTS:
      The mean IOP of all eyes was decreased significantly by 1.8, 2.9, and 2.3 mmHg at
      1, 2, and 3 months after the switch from unoprostone to latanoprost treatment.
      The IOP of patients with an initial IOP of <or=12 or >12 mmHg was reduced by 11.0
      or 19.9%, respectively, after 3 months on latanoprost. The IOP of 30 (88.2%) of
      the 34 eyes was further reduced by the switch from unoprostone to latanoprost.
      CONCLUSIONS: Latanoprost reduced the IOP of NTG patients who had already been
      treated with unoprostone, even though both drugs are prostaglandin-related.
      Switching to latanoprost might thus achieve a maximal decrease in IOP and thereby
      better prevent damage to the optic nerve and loss of visual field in NTG
      patients.

PMID- 16897219
TI  - Choroidal neovascularization in highly myopic eyes after cataract surgery.
AB  - PURPOSE: To determine the incidence and characteristics of choroidal
      neovascularization (CNV) in patients with high myopia (>or=8 diopters) who
      underwent cataract surgery in the Department of Ophthalmology, Tokyo Medical and
      Dental University, or the Ohno Eye Clinic, Tokyo, between September 1991 and
      March 2000. METHODS: The medical records of 35 patients (48 eyes) who underwent
      cataract surgery with phacoemulsification and intraocular lens implantation were
      studied retrospectively. The development of CNV over a 4-year follow-up period,
      and its characteristics were determined. All of the eyes had received a
      comprehensive ophthalmological examination, including best-corrected visual
      acuity measurements, anterior segment biomicroscopy, and a dilated fundus
      examination by stereoscopic observation. RESULTS: CNV was found in six eyes
      (12.5%) of six patients. The mean interval between cataract surgery and the
      development of CNV was 34+/-17 months (range, 12-48 months). The CNV was
      subfoveal in all cases. The mean logarithm of the minimum angle of resolution
      (logMAR) after cataract surgery and before the appearance of CNV was 0.23+/-0.24,
      and 0.93+/-0.41 after the CNV appeared. This decrease was statistically
      significant (P=0.0008, paired Student t test). Subfoveal CNV developed more
      frequently in eyes when the fellow eye showed evidence of CNV preoperatively
      (40.0%) than in eyes when the fellow eye exhibited no evidence of CNV (9.3%).
      CONCLUSIONS: CNV developed in 12.5% of patients with high myopia after cataract
      surgery. CNV tended to develop more frequently when the fellow eye had CNV.

PMID- 16897220
TI  - Long-term retention of dye after indocyanine green-assisted internal limiting
      membrane peeling.
AB  - PURPOSE: To evaluate dye retention in the fundus after indocyanine green (ICG)
      assisted internal limiting membrane peeling. METHODS: Ten eyes with stage 3 or 4
      nondiabetic idiopathic macular hole (MH group) and six eyes with diffuse diabetic
      macular edema (DM group) were studied. The fundus was examined with 780-nm
      infrared illumination by a scanning laser ophthalmoscope (SLO) after ICG-assisted
      internal limiting membrane peeling. The postoperative follow-up period ranged
      from 6 to 12 months (mean+/-SD, 3.7+/-2.6 months). RESULTS: Fluorescence from ICG
      was detected in all studied eyes in both groups up to 6 months after surgery. At
      9 months after surgery, ICG fluorescence was visible in all eyes of the DM group,
      but in only one-third of eyes of the MH group. No fluorescence was detected in
      fellow eyes that had not been operated on. CONCLUSION: The present study using
      SLO revealed that ICG remains in the fundus for over 6 months after surgery. The
      results also suggested that a longer time might be required for dye clearance
      from the diabetic retina than from the nondiabetic retina.

PMID- 16897221
TI  - Polypoidal choroidal vasculopathy and retinochoroidal anastomosis in Japanese
      patients eligible for photodynamic therapy for exudative age-related macular
      degeneration.
AB  - PURPOSE: To determine the percentage of Japanese patients with age-related
      macular degeneration (AMD) who are eligible for photodynamic therapy (PDT) with
      verteporfin who have either polypoidal choroidal vasculopathy (PCV) or choroidal
      neovascularization (CNV) with retinochoroidal anastomosis (RCA). METHODS: The
      medical charts of 82 consecutive patients (83 eyes) with subfoveal CNV due to AMD
      were reviewed. Initially, we determined which of these eyes were eligible for PDT
      by using the criteria reported by two large randomized control studies, that is,
      the Treatment of Age-related Macular Degeneration with Photodynamic Therapy (TAP)
      study and the Verteporfin in Photodynamic Therapy (VIP) study. Among the PDT
      eligible patients, the percentage of eyes with PCV or CNV with RCA was determined
      by indocyanine green angiography (ICGA). RESULTS: In total, 36 eyes (43%) of the
      83 eyes were PDT-eligible; 17 (20%) based on the TAP study criteria, and 19 (23%)
      based on the VIP study criteria. Among these PDT-eligible eyes, ICGA revealed
      that 12 (33%) had PCV and 2 (6%) had CNV with RCA. CONCLUSIONS: With ICGA, PCV or
      CNV with RCA were recognized in a substantial proportion of cases eligible for
      PDT based on the two clinical studies. Considering that the treatment efficacy of
      PDT for PCV or RCA has not been established, detection of PCV or RCA prior to PDT
      with ICGA is highly recommended.

PMID- 16897223
TI  - Changes of oscillatory potentials and photopic negative response in patients with
      early diabetic retinopathy.
AB  - PURPOSE: To investigate the clinical significance of the oscillatory potentials
      (OPs) and photopic negative response (PhNR) of the electroretinogram (ERG) in
      patients with early diabetic retinopathy. METHODS: One hundred two diabetic
      patients with diabetic retinopathy at different stages were examined. Thirty-two
      age-matched normal controls were also studied. Full-field maximal and photopic
      cone ERGs were recorded. The amplitudes and implicit times of the OPs, cone b
      wave, and PhNR were compared at the different stages of diabetic retinopathy.
      RESULTS: The a and b wave amplitudes of the maximal scotopic ERGs remained
      unchanged despite advancing stages of retinopathy, but the OP amplitudes were
      significantly attenuated even at an early stage of diabetic retinopathy. The
      amplitudes of both the PhNR and cone b wave were reduced at an early stage of
      diabetic retinopathy. Analysis of the receiver operating characteristic curves
      demonstrated that the amplitudes and implicit times of the OPs were more
      sensitive and specific than those of the PhNR in detecting changes of retinal
      function in the early stages of diabetic retinopathy. CONCLUSIONS: The amplitudes
      of the OPs and PhNR progressively decrease with the progression of diabetic
      retinopathy. The PhNR amplitudes were reduced along with the cone b wave,
      indicating that earlier change of the PhNR in diabetic patients reflects reduced
      input to the retinal ganglion cell from the distal retina. The amplitudes and
      implicit times of the OPs are better indicators than those of the PhNR in
      detecting functional decreases in patients with early diabetic retinopathy.

PMID- 16897222
TI  - Feasibility study on computer-aided screening for diabetic retinopathy.
AB  - PURPOSE: To conduct a feasibility study of computer-aided screening for diabetic
      retinopathy by developing a computerized program to automatically detect retinal
      changes from digital retinal images. METHODS: The study was carried out in three
      steps. Step 1 was to collect baseline retinal image data of 600 eyes of normal
      subjects with normal fundi and data of 300 eyes of diabetic patients with
      diabetic retinopathy. All data were recorded by digital fundus camera. Step 2 was
      to analyse all retinal images for normal and abnormal features. By this method,
      the automated computerized screening program was developed. The program
      preprocesses colour retinal images and recognizes the main retinal components
      (optic disc, fovea, and blood vessels) and diabetic features such as exudates,
      haemorrhages, and microaneurysms. All of the accumulated information is
      interpreted as normal, abnormal, or unknown. Step 3 was to evaluate the
      sensitivity and specificity of the computerized screening program by testing the
      program on diabetic patients and comparing the program's results with the results
      of screening by retinal specialists. RESULTS: Diabetic patients (182 patients,
      336 eyes) were examined by retinal specialists; 221 eyes had a normal fundus and
      115 eyes had nonproliferative diabetic retinopathy. Digital retinal images were
      taken of these 336 eyes and interpreted by the automated screening program. The
      program had a sensitivity and specificity of 74.8% and 82.7%, respectively.
      CONCLUSIONS: The automated screening program was able to differentiate between
      the normal fundus and the diabetic retinopathy fundus. The program may be
      beneficial for use in screening for diabetic retinopathy. Further development of
      the program may provide higher sensitivity.

PMID- 16897224
TI  - Adenoid cystic carcinoma arising from the lower eyelid.
AB  - BACKGROUND: Primary cutaneous adenoid cystic carcinoma is one of the rarest
      eyelid tumors. CASE: A 39-year-old man presented with a small subcutaneous
      induration in his left lower eyelid close to the lower lacrimal punctum.
      OBSERVATIONS: Under a clinical diagnosis of chalazion, the eyelid induration was
      extracted surgically via the palpebral conjunctiva. Histopathological examination
      of the extracted tumor revealed proliferation of basaloid cells with a prominent
      cribriform pattern containing Alcian blue-positive and periodic acid Schiff
      positive material, leading to a diagnosis of adenoid cystic carcinoma. The
      patient subsequently underwent extended radical excision including the lacrimal
      sac. No recurrence was observed during 20 months after surgery. CONCLUSIONS:
      Adenoid cystic carcinoma should be considered as a differential diagnosis of
      eyelid tumors simulating chalazion. Adenoid cystic carcinoma in the eyelid may
      have a more favorable prognosis than that in the lacrimal gland.

PMID- 16897226
TI  - Recovery of reliability by retest after a 5-minute interval in frequency doubling
      technology perimetry.
AB  - PURPOSE: In frequency doubling technology (FDT) perimetry, the incidence of tests
      classified as unreliable is higher in the second-tested left eye than in the
      first-tested right eye when perimetry is performed without a rest period. The
      purpose of this study was to determine whether the incidence of unreliable
      results was reduced when the retest began after a 5-min rest period. METHODS: The
      subjects were 978 residents of Miyoshi City, Japan, who underwent FDT perimetry
      during a medical checkup. FDT perimetry was always performed first on the right
      eye and then on the left eye without a rest interval. When the results were
      determined to be unreliable, FDT perimetry was repeated after a 5-min rest
      interval. RESULTS: The perimetric results were determined to be unreliable in one
      eye of 119 subjects; the results of the first-tested right eye were unreliable in
      24 (20.2%), and the results of the second-tested left eye were unreliable in 95
      (79.8%) subjects. This difference in the incidence of reliability was significant
      (P<0.001). After a 5-min rest interval, the percentage of eyes with reliable
      results recovered to 92% of the right eyes and to 86% of the left eyes.
      CONCLUSIONS: The incidence of unreliable results in FDT perimetry of the second
      tested left eye was higher than that of the first-tested right eye when tests
      were performed without a rest interval. However, the incidence of unreliability
      in the eye was decreased when the retest was performed after a 5-min rest
      interval.

PMID- 16897225
TI  - Inhibitory effect of bucillamine on the increased leukocyte entrapment in the
      retinal microcirculation of diabetic rats.
AB  - PURPOSE: To evaluate quantitatively the effects of bucillamine on the entrapment
      of leukocytes in the retinal microcirculation of diabetic rats. METHODS: 13 male
      Brown Norway rats were injected with streptozotocin (STZ). After the animals
      developed diabetes, they were divided into two groups. Group 1 (n=7) received
      fresh drinking water without bucillamine, and group 2 (n=6) received fresh
      drinking water supplemented with bucillamine (200 mg/kg per day). Rats that were
      not injected with STZ and received water without bucillamine served as controls
      (n=6). Four weeks after the injection of STZ, the leukocytes in the retina were
      observed by acridine orange digital fluorography. The number of leukocytes
      trapped in the retinal vessels was compared among the three groups. RESULTS: In
      the untreated diabetic rats, the number of trapped leukocytes was significantly
      higher than in control rats or bucillamine-treated diabetic rats (P<0.05).
      CONCLUSIONS: We demonstrated an inhibitory effect of bucillamine on leukocyte
      entrapment in the retinal vessels of diabetic rats. Bucillamine may have
      therapeutic efficacy in preventing the development of diabetic retinopathy.

PMID- 16897227
TI  - Sensitivity and specificity of new eye check chart for neuro-ophthalmological
      diseases.
AB  - PURPOSE: To determine the sensitivity and specificity of a new Eye Check Chart
      (ECC) for screening neuro-ophthalmological patients with lesions in the visual
      pathways. METHODS: The Humphrey perimeter (HP) with the 30-2 SITA Fast program
      was used to confirm the visual field defects found in 65 eyes of 35 neuro
      ophthalmological patients. Forty eyes had pregeniculate lesions, and 25 eyes had
      postgeniculate lesions. As controls, 22 eyes of 12 patients without visual field
      defects were also examined. All subjects were then examined using the eye check
      chart (ECC) to determine whether comparable visual field defects were detected.
      The eyes were separated into those in which the ECC findings agreed with the HP
      findings, and those in which they did not agree. Based on HP results, the
      sensitivity and specificity of the ECC results were calculated. RESULTS: The
      sensitivity of ECC was 87% in patients with pregeniculate lesions and 80% in
      patients with postgeniculate lesions. The overall specificity of ECC was 91%.
      CONCLUSION: This high sensitivity and specificity indicate that ECC can give
      reliable results in screening neuro-ophthalmological patients for lesions in the
      visual pathways.

PMID- 16897228
TI  - Two new devices for dacryocystorhinostomy.

PMID- 16897229
TI  - Peripheral T-cell lymphoma of the eyelid.

PMID- 16897230
TI  - Cystoid macular edema related to diabetic retinopathy with retinitis pigmentosa.

PMID- 16897231
TI  - A case of branch retinal artery occlusion associated with presumed optic
      neuritis.

PMID- 16897232
TI  - Migrainous cerebral infarction triggered by alcohol intake under the burning sun.

PMID- 16897233
TI  - Effects of sivelestat, a new elastase inhibitor, on IL-8 and MCP-1 production
      from stimulated human alveolar epithelial type II cells.
AB  - PURPOSE: The alveolar epithelial cell type II (AEC-II) is itself able to amplify
      lung inflammation by producing inflammatory cytokines and chemokines, leading to
      the activation and recruitment of phagocytes. Sivelestat, a new neutrophil
      elastase inhibitor, has been shown to attenuate acute lung injury in animal
      experiments. In the current study, we assessed the effects of sivelestat on the
      production of chemokines from cultured A549 cells, a human AEC-II-like cell line.
      METHODS: A549 cells were stimulated with endotoxin or tumor necrosis factor-alpha
      in the presence of sivelestat (1-100 microg x ml(-1)). Culture supernatant levels
      of interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) were
      determined by enzyme-linked immunosorbent assay. The expression of IL-8 and MCP-1
      mRNAs in stimulated A549 cells in the presence of sivelestat (100 microg x ml(
      1)) was quantified by real-time polymerase chain reaction. RESULTS: Sivelestat,
      at 100 microg x ml(-1) reduced the accumulation of IL-8 and MCP-1 in the culture
      medium. The high dose of sivelestat significantly inhibited the expression of IL
      8 mRNA in A549 cells. The drug also decreased MCP-1 mRNA expression, although not
      significantly. CONCLUSION: These data suggest that a high dose of sivelestat
      regulates the production of IL-8 and MCP-1 in AEC-II.

PMID- 16897234
TI  - Effect of humidifying devices on the measurement of tidal volume by mechanical
      ventilators.
AB  - PURPOSE: We hypothesized that expiratory tidal volume was underestimated, because
      a heat-moisture exchanger traps the expired vapor. We, therefore, designed
      patient and bench studies to investigate the accuracy of tidal volume monitoring.
      METHODS: In a patient study, applying two humidifying systems (a heat-moisture
      exchanger and a heated humidifier) and two tidal volumes (12 and 6 ml x kg(-1))
      with a Servo ventilator 300, we recorded the displayed expiratory tidal volume
      and thoracic volume displacement, measured by respiratory inductive
      plethysmography. Temperature, relative humidity, and absolute humidity were
      measured at the airway opening and at the end of the expiratory limb. Using a
      model lung, we also tested three different ventilators (Puritan-Bennett 7200ae,
      Evita 4, and Servo ventilator 300) to investigate whether the effects of the heat
      moisture exchanger and the heated humidifier on monitored tidal volume varied
      according to the brand of ventilator. RESULTS: With the use of the heat-moisture
      exchanger, the displayed expiratory tidal volume was significantly smaller, by
      12%-14%, than that with the heated humidifier, although thoracic volume
      displacement was identical in the two systems. The temperature and absolute
      humidity at the end of the expiratory limb were significantly lower with the heat
      moisture exchanger than with the heated humidifier. In the model lung study, we
      investigated the effects of different brands of ventilator on the expiratory
      tidal volume. A similar degree (8%-14%) of underestimation of tidal volume was
      observed with the heat-moisture exchanger, regardless of ventilator brand.
      CONCLUSION: Monitored expiratory tidal volume was underestimated by approximately
      10%, when using a heat-moisture exchanger.

PMID- 16897235
TI  - Nitrous oxide can enhance the hypnotic effect, but not the suppression of spinal
      motor neuron excitability by propofol in humans.
AB  - PURPOSE: We investigated whether nitrous oxide can enhance the suppressive effect
      of propofol on spinal motor neuron excitability in humans. METHODS: Sixteen adult
      patients were prospectively randomly assigned to be given either propofol alone
      (group P; n = 8) or a supplement of 66% nitrous oxide with propofol (group PN; n
      = 8) for intraoperative sedation. Propofol was administered by a target
      controlled infusion system to maintain sequentially increasing plasma propofol
      concentrations (Cpt) of 0.5, 0.8, 1.0, 1.3, 1.5 and 1.8 microg x ml(-1) in all
      patients. Assessment of the patient's level of sedation in both groups was
      performed with the Wilson Sedation Scale (WSS). F-wave analysis on the left
      abductor pollicis brevis muscle was carried out for the assessment of spinal
      motor neuron excitability at each plasma propofol concentration. RESULTS:
      Significant differences in the WSS scores between group P and group PN were
      observed at 0.8, 1.0, 1.3, and 1.5 microg x ml(-1) of Cpt (group P < group PN; P
      < 0.01). Cpt greater than 1.0 microg x ml(-1) significantly reduced F-wave
      persistence in a concentration-dependent manner, and the ICpt 50 and ICpt 95
      values for plasma propofol concentration (plasma propofol concentrations that
      produced 50% and 95% inhibition of the baseline, respectively) were 1.05 and 1.95
      microg x ml(-1) in group P, and 1.07 and 2.14 microg x ml(-1) in group PN,
      respectively. CONCLUSION: These results suggest that nitrous oxide can enhance
      the hypnotic effect, but not the suppression of spinal motoneuron excitability by
      propofol in humans at clinical levels of Cpt.

PMID- 16897236
TI  - Effects of a protease inhibitor, ulinastatin, on coagulation and fibrinolysis in
      abdominal surgery.
AB  - PURPOSE: Ulinastatin is well known to inhibit the activity of polymorphonuclear
      leukocyte elastase (PMNE). The PMNE concentration correlates with the activities
      of coagulation and fibrinolysis. The purpose of the present study was to
      investigate the effects of ulinastatin, a protease inhibitor, on coagulation and
      fibrinolysis in abdominal surgery. METHODS: Thirty patients, aged 40 to 70 years,
      with American Society of Anesthesiologists (ASA) physical status I or II,
      scheduled for major abdominal surgery, were enrolled. Anesthesia was induced with
      midazolam and thiopental, and was maintained with sevoflurane, nitrous oxide in
      oxygen, and an epidural block. An infusion of ulinastatin, 6000 units x kg(-1) in
      30 min, was started 1 h after the start of surgery in the ulinastatin group (15
      patients). In the control group (15 patients), no protease inhibitors were
      infused. White blood cell count; platelet count; prothrombin time; activated
      partial thromboplastin time; and plasma concentrations of PMNE, antithrombin
      (AT), fibrin/fibrinogen degradation product (FDP), fibrinogen, plasminogen,
      plasmin-(alpha2) plasmin inhibitor complex (PIC), and thrombin-antithrombin
      complex (TAT) were measured before, at the end of, and 12 h after surgery.
      RESULTS: TAT, PIC, and FDP after surgery were significantly lower in the
      ulinastatin group than in the control group. AT was decreased in the control
      group but not in the ulinastatin group, with significant differences between the
      two groups. CONCLUSION: Ulinastatin could inhibit coagulation and fibrinolysis in
      abdominal surgery.

PMID- 16897237
TI  - Effects of landiolol on hemodynamic response and seizure duration during
      electroconvulsive therapy.
AB  - PURPOSE: This study was done to evaluate the effect of landiolol, an ultra-short
      acting beta-blocker, on the hemodynamic response and the duration of seizure
      activity during electroconvulsive therapy (ECT). METHODS: We designed a
      prospective, randomized, double-blinded, placebo-controlled, crossover study.
      Fourteen psychiatric patients participated. Landiolol (0.1 mg x kg(-1) or 0.2 mg
      x kg(-1)) or saline (placebo) was administered IV 1 min before the induction of
      anesthesia. Unconsciousness was induced with propofol 1.0 mg x kg(-1) IV, and
      muscle paralysis was produced with succinylcholine 0.6 mg x kg(-1) IV.
      Subsequently, electrical stimulus was administered to elicit a seizure, and the
      duration of the motor seizure activity was noted. RESULTS: The heart rate (HR)
      and rate-pressure product (RPP) before ECT were significantly decreased in the
      0.2 mg x kg(-1) landiolol group compared with these parameters in the placebo and
      0.1 mg x kg(-1) landiolol groups. Both the 0.1 mg x kg(-1) and 0.2 mg x kg(-1)
      doses significantly attenuated the degree of tachycardia and RPP after ECT in
      comparison with the placebo group. Pretreatment with 0.2 mg x kg(-1) landiolol
      resulted in a significantly shorter duration of motor seizure than that in the
      placebo group (21 +/- 13 s vs 27 +/- 12 s). CONCLUSION: As the landiolol dose of
      0.2 mg x kg(-1) caused shorter seizure duration, and because the hemodynamic
      effects after ECT of the 0.1 mg x kg(-1) and 0.2 mg x kg(-1) doses were similar,
      it was concluded that a 0.1 mg x kg(-1) landiolol bolus was the appropriate dose
      pretreatment before ECT.

PMID- 16897238
TI  - Omission of fentanyl during sevoflurane anesthesia decreases the incidences of
      postoperative nausea and vomiting and accelerates postanesthesia recovery in
      major breast cancer surgery.
AB  - PURPOSE: Our purpose was to investigate the effect of omission of fentanyl during
      sevoflurane anesthesia on the incidences of postoperative nausea and vomiting and
      on postanesthesia recovery in female patients undergoing major breast cancer
      surgery. METHODS: Female patients (American Society of Anesthesiologists [ASA]
      physical status [PS] class I-II; age, 28-84 years) undergoing major breast cancer
      surgery were randomized to one of two anesthesia maintenance groups: sevoflurane
      fentanyl anesthesia (SF; n = 25) or fentanyl-free sevoflurane anesthesia (S; n =
      26). All patients were administered with propofol 2 mg x kg(-1) intravenously for
      anesthesia induction, a laryngeal mask airway was placed, and they received
      rectal diclofenac and local infiltration anesthesia. Anesthesia was maintained
      with sevoflurane in oxygen-air and they breathed spontaneously. The patients in
      group SF received fentanyl 0.1 mg intravenously and those in group S received
      normal saline during anesthesia. RESULTS: Group SF revealed higher incidences of
      postoperative nausea (68% vs 27%) and vomiting (32% vs 8%) in the first 24
      postoperative hours than group S. The median (25th-75th percentile) length of
      time from postanesthesia care unit (PACU) admission to ambulation was
      significantly longer in group SF (n = 23) at 195 min (158-219 min), than in group
      S, at 141 min (101-175 min). Two patients in group SF could not walk during the
      PACU stay. CONCLUSION: Omission of fentanyl during sevoflurane anesthesia,
      combined with diclofenac and local infiltration anesthesia, decreases the
      incidences of postoperative nausea and vomiting and accelerates postanesthesia
      recovery in patients undergoing major breast cancer surgery.

PMID- 16897239
TI  - Increase in intracellular Ca2+ concentration is not the only cause of lidocaine
      induced cell damage in the cultured neurons of Lymnaea stagnalis.
AB  - PURPOSE: To determine whether the increase in intracellular Ca2+ concentration
      induced by lidocaine produces neurotoxicity, we compared morphological changes
      and Ca2+ concentrations, using fura-2 imaging, in the cultured neurons of Lymnaea
      stagnalis. METHODS: We used BAPTA-AM, a Ca2+ chelator, to prevent the increase in
      the intracellular Ca2+ concentration, and Calcimycin A23187, a Ca2+ ionophore, to
      identify the relationship between increased intracellular Ca(2+) concentrations
      and neuronal damage without lidocaine. Morphological changes were confirmed using
      trypan blue to stain the cells. RESULTS: Increasing the dose of lidocaine
      increased the intracellular Ca2+ concentration; however, there was no
      morphological damage to the cells in lidocaine at 3 x 10(-3) M. Lidocaine at 3 x
      10(-2) M increased the intracellular Ca2+ concentration in both saline (from 238
      +/- 63 to 1038 +/- 156 nM) and Ca2+-free medium (from 211 +/- 97 to 1046 +/- 169
      nM) and produced morphological damage and shrinkage, with the formation of a
      rugged surface. With the addition of BAPTA-AM, lidocaine at 3 x 10(-2) M
      moderately increased the intracellular Ca2+ concentration (from 150 +/- 97 to 428
      +/- 246 nM) and produced morphological damage. These morphologically changed
      cells were stained dark blue with trypan blue dye. The Ca2+ ionophore increased
      the intracellular Ca2+ concentration (from 277 +/- 191 to 1323 +/- 67 nM) and
      decreased it to 186 +/- 109 nM at 60 min. Morphological damage was not observed
      during the 60 min, but became apparent a few hours later. CONCLUSION: These
      results indicated that the increase in intracellular Ca2+ concentration is not
      the only cause of lidocaine-induced cell damage.

PMID- 16897240
TI  - Effects of dexmedetomidine on cerebral circulation and systemic hemodynamics
      after cardiopulmonary resuscitation in dogs.
AB  - PURPOSE: Our purpose was to examine the effect of dexmedetomidine, when used with
      phenylephrine during cardiopulmonary resuscitation (CPR), on the cerebral and
      systemic circulations. METHODS: In pentobarbital-anesthetized, mechanically
      ventilated dogs, we evaluated pial vessel diameters, cerebral oxygen extraction,
      and systemic hemodynamics before and after cardiac arrest (5 min) and
      resuscitation, in the presence or absence of dexmedetomidine (n = 7 each;
      dexmedetomidine or control group). RESULTS: In both groups: (a) pial arterioles
      were dilated at 5 and 15 min after CPR, and had returned to baseline diameters at
      30 min; (b) sagittal sinus pressure was significantly raised at 5 and 15 min
      after CPR; and (c) cerebral oxygen extraction was decreased at 5, 15, and 30 min
      after CPR, and had returned to baseline level at 60 min after CPR. We could find
      no differences between the two groups in the cerebral circulation after CPR.
      However, the number of defibrillation electric shocks required to restore
      spontaneous circulation (5.5 vs 3.6; P < 0.05), the dose of phenylephrine used
      for CPR (1193 microg vs 409 microg; P < 0.01), and the number of
      postresuscitation ventricular ectopic beats observed during the first 120 min
      after successful resuscitation (1606 vs 348; P < 0.05) were all significantly
      lower in the dexmedetomidine group. CONCLUSION: Although intravenous
      dexmedetomidine, as used for CPR, does not have a beneficial effect on either
      cerebral vessels or cerebral oxygen extraction, it may reduce the number of
      defibrillation shocks needed and the number of postresuscitation ventricular
      ectopic beats, and help to bring about stable systemic circulation after CPR.

PMID- 16897241
TI  - Combined effects of propofol and mild hypothermia on cerebral metabolism and
      blood flow in rhesus monkey: a positron emission tomography study.
AB  - PURPOSE: Propofol reduces the cerebral metabolic rate for oxygen (CMRO2),
      regional CMRO2 (rCMRO2), cerebral blood flow (CBF), and regional CBF (rCBF), but
      maintains the coupling of cerebral metabolism and blood flow. Under mild to
      moderate hypothermia, the coupling is maintained, while rCBF is reduced, but no
      direct measurement of rCMRO2 has yet been reported. This study aimed to evaluate
      the effects of propofol under normothermic and mild hypothermic temperatures upon
      rCMRO2, rCBF, and their regional coupling, through direct measurement by positron
      emission tomography. METHODS: Rhesus monkeys were anesthetized with 65% nitrous
      oxide and propofol. Then rCBF and rCMRO2 were measured under four sets of
      conditions: infusion of a low-propofol dose (12 mg.kg(-1) x h(-1)) at
      normothermic temperatures (38 degrees C), a high dose (25 mg x kg(-1) x h(-1)) at
      normothermic temperatures, a low dose under mild hypothermia (35 degrees C), and
      a high dose under mild hypothermia. The ratio of rCBF/rCMRO(2) was calculated
      from these data. RESULTS: Reductions in CMRO2 and rCMRO2 in most regions were
      associated with two factors: the higher propofol dose and the induction of
      hypothermia, but there was no interaction between these factors. Concerning blood
      flow, no significant reduction was observed, except for CBF by the induction of
      hypothermia. The ratio of rCBF/rCMRO2 was constant in this study setting.
      CONCLUSION: During propofol anesthesia, it is possible to reduce cerebral
      metabolism throughout the entire brain as well as in any brain region by
      increasing the propofol dose or inducing hypothermia. The concurrent use of these
      two interventions has an additive effect on metabolism, and can be considered as
      safe, as their combination does not impair the coupling of cerebral metabolism
      and blood flow.

PMID- 16897242
TI  - Pre-anesthetic evaluation can play a crucial role in the determination of airway
      management in a child with oropharyngeal tumor.
AB  - We experienced a case of a huge hemangioma occupying the oropharyngeal space in
      an 11-year-old child. Although urgent surgical tracheostomy under local
      anesthesia was suggested initially, medical interview and findings of
      computerized tomography and fiberoptic laryngoscopy revealed that the airway of
      the patient was relatively stable when she was in the semi-left decubitus
      position. General anesthetic induction would have had potential risks of airway
      obstruction. Thus, after placing the patient in the semi-left decubutus position,
      we chose semi-awake induction to secure the airway. With a small dose of
      fentanyl, we accomplished orotracheal intubation. In this report, we discuss the
      importance of referring to an airway management algorithm when encountering a
      difficult airway.

PMID- 16897243
TI  - Anesthetic management of bidirectional cavopulmonary shunt in a patient with
      pulmonary atresia with intact ventricular septum associated with sinusoidal
      communications.
AB  - Pulmonary atresia with intact ventricular septum (PAIVS) is sometimes associated
      with coronary artery anomalies, including right ventricle (RV)-to-coronary artery
      fistulas (sinusoidal communications), coronary artery stenoses, and coronary
      artery occlusions. In some cases, the coronary circulation depends entirely or
      partly on the desaturated systemic venous blood supply from the RV. Under these
      circumstances, decompression of the RV can result in fatal myocardial ischemia. A
      6-month-old boy, diagnosed with PAIVS associated with sinusoidal communications,
      underwent a bidirectional cavopulmonary shunt procedure under venoarterial
      cardiopulmonary bypass (CPB). During CPB, to prevent RV decompression, we
      maintained right atrial pressure above 5 mmHg and used a pump perfusion rate of
      30%-40% of the calculated value based on body surface area. Although
      electrocardiography showed slight ST depression and bradycardia, myocardial
      contractility after weaning from CPB was adequate to maintain the circulation
      with the administration of dobutamine and atrial pacing. In patients with PAIVS
      and RV-dependent coronary circulation, it is important to maintain coronary
      artery perfusion throughout the period of anesthesia.

PMID- 16897244
TI  - Spinal anesthesia using a continuous spinal catheter for cesarean section in a
      parturient with prior surgical correction of scoliosis.
AB  - This case report demonstrates the successful anesthetic management of cesarean
      section for a 29-year-old primiparous parturient with a past history of a
      scoliosis operation at 13 years of age. An Isola hook and screw-rod system had
      been implanted as posterior spinal instrumentation at the level of T3-L3. We
      titrated hyperbaric bupivacaine 7 mg combined with fentanyl 15 microg through a
      continuous spinal catheter, placed with a catheter-over-needle technique in order
      to avoid unintentional wide spread of anesthetic agents. The anesthetic level was
      T4 at the start of the operation. Her surgery was carried out without any
      problems. Headache, as a dural tap-related complication, was not observed. Spinal
      anesthesia with the titration of anesthetic agents for cesarean section is
      considered to be one of the choices for a parturient who has had spinal
      instrumentation.

PMID- 16897245
TI  - Anesthetic management of a patient with a history of Batista procedure for
      dilated cardiomyopathy undergoing gastric surgery.
AB  - We experienced anesthetic management for an operation to remove a hemorrhagic
      gastric submucosal tumor in a patient who had undergone left ventricular volume
      reduction (the Batista procedure) for dilated cardiomyopathy (DCM) 2 years
      previously. Preoperative evaluations indicated the relapse of severe DCM.
      Intravenous and epidural anesthesia was employed with the aid of an intraaortic
      balloon pump (IABP). Safe anesthetic management was achieved under the guidance
      of a Swan-Ganz catheter without inducing overreduction of afterload or excessive
      preload.

PMID- 16897246
TI  - Identification of the lumbar intervertebral level using ultrasound imaging in a
      post-laminectomy patient.
AB  - A spinal block was performed in a post-laminectomy patient, using both ultrasound
      imaging and X-ray imaging. Ultrasound imaging clearly identified the L3/4
      intervertebral level, the spinal canal, the corpus vertebrae, and the dura mater.
      Using ultrasound imaging, we measured the distance from the skin surface to the
      dura mater (39 mm). A 25-G needle for the spinal block was accurately advanced
      into the spinal canal with the use of X-ray imaging (43 mm from the skin to the
      subarachnoid space). We report here that ultrasound imaging was useful for
      performing a spinal block in a post-laminectomy patient in whom there was
      anatomical change around the spine.

PMID- 16897247
TI  - Repeated dexmedetomidine infusions, a postoperative living-donor liver
      transplantation patient.
AB  - Here we report on a postoperative living-donor liver transplantation (LDLT)
      patient who received nightly infusions of dexmedetomidine (DEX), a specific
      alpha2-adrenergic receptor agonist, to treat agitation and insomnia during an
      intensive care unit stay. The infusion rate was adjusted according to the Ramsay
      sedation score. The actual plasma concentrations were higher than the values
      predicted by RugLoop software package simulation 9 h after the DEX infusion.
      However, all of the measurements were within the therapeutic range for DEX. Thus,
      DEX infusion could be safely used in the postoperative LDLT patient by employing
      a simple consciousness scale.

PMID- 16897248
TI  - Postoperative airway obstruction after airway tumor debulking.
AB  - Postoperative airway obstruction is a relatively common complication after
      anesthesia, occurring most often after head and neck surgery. We present a case
      of postoperative airway obstruction in a patient who underwent airway tumor
      debulking. This case demonstrates that, in high-risk patients, despite the
      traditional methods of determining eligibility for extubation, postoperative
      airway obstruction can still occur, and alternative means of extubation should be
      considered.

PMID- 16897249
TI  - Comparison between neurotropin and mepivacaine for stellate ganglion injection.
AB  - Neurotropin, a nonproteinaceous extract from the inflamed skin of rabbits
      inoculated with vaccinia virus, is reported to decrease pain effectively when
      used for stellate ganglion (SG) injection. We compared the effects of neurotropin
      SG injection with those of mepivacaine on pain relief, as well as comparing the
      side effects. One hundred and eighty-eight SG injections in 15 patients (5 with
      postherpetic neuralgia and 10 with sudden deafness) were performed either with 1%
      mepivacaine 6 ml or with neurotropin 3 ml combined with saline 3 ml in turn.
      Fifteen min before and after the injection, the pain score, according to a visual
      analog scale (VAS; only in patients with postherpetic neuralgia); blood pressure;
      and heart rate were checked, and the number of procedures with Horner's sign was
      determined. VAS scores decreased significantly with both injections. Horner's
      sign was observed on the block side in all procedures with the mepivacaine
      injection, but it was seen in only 48 procedures with the neurotropin injection.
      Blood pressure and heart rate did not change. In conclusion, the SG injection of
      neurotropin decreased the VAS score in postherpetic neuralgia to the same extent
      as mepivacaine. The incidence of Horner's sign was significantly lower with
      neurotropin than with mepivacaine.

PMID- 16897250
TI  - Rectal luminal Pr(CO2), measured by automated air tonometry, does not reflect
      gastric luminal Pr(CO2) in children.
AB  - Rectal luminal regional P(CO2) (Pr(CO2)) was compared with gastric luminal
      Pr(CO2) measured by automated air tonometry at intervals of 10 min in 20 children
      aged 6-16 years scheduled for elective surgery under general anesthesia. In 5
      patients, measurement of rectal Pr(CO2) failed because of catheter-related
      problems. In the remaining 15 children, aged 10.6 +/- 2.5 years, 19 +/- 7 paired
      rectal and gastric Pr(CO2) values (n total, 241) were measured. Bias and
      precision for gastric compared to rectal Pr(CO2) was -1.79 kPa and 2.89 kPa. In
      patients with obvious feces in the rectum, bias (precision) for gastric compared
      to rectal Pr(CO2) was -2.7 kPa (2.6 kPa) and in those with empty rectum, -0.75
      kPa (1.42 kPa; t-test; P < 0.001). Based on our in vivo data, rectal luminal
      Pr(CO2), measured by automated air tonometry, does not reflect gastric luminal
      Pr(CO2) in children. Enteral luminal gas production within feces in the rectum
      seems to be a major source of this disagreement.

PMID- 16897251
TI  - Hypothermia decreases ethanol MAC in rats.
AB  - Despite the known capacity of hypothermia to increase anesthetic potency
      (decrease the partial pressure required to produce anesthesia), many in vitro
      studies examine the effects of ethanol and other anesthetics in oocytes or
      isolated neurons at room temperature. We tested whether, as predicted for potent
      inhaled anesthetics, a proportionate increase in solubility with hypothermia
      matched a decrease in ethanol minimum alveolar concentration (MAC), and thereby
      made the use of a single anesthetic concentration appropriate regardless of
      temperature. We determined ethanol MAC in normothermic (37.3 degrees C) and
      hypothermic (28.5 degrees C) rats, and, at the two temperatures, also determined
      ethanol solubilities in olive oil and saline. Ethanol MAC decreased, while olive
      oil/gas and saline/gas partition coefficients increased. However, the increase in
      the saline/gas partition coefficient did not match the decrease in MAC, and thus
      the aqueous-phase partial pressure producing absence of movement in 50% of rats
      (EC50) values for ethanol decreased by 17%. Although this decrease is not large,
      it may be important for comparative estimates of the in vitro effects of ethanol
      at different temperatures.

PMID- 16897254
TI  - Repetitive acute shock following tracheal extubations after neurosurgery for a
      cerebellar tumor.

PMID- 16897253
TI  - Use of landiolol in the perioperative management of supraventricular tachycardia.

PMID- 16897252
TI  - Sciatic nerve palsy after total hip arthroplasty in a patient receiving psoas
      compartment block for patient-controlled regional analgesia.

PMID- 16897255
TI  - Transient phlebitis and propofol: deja vu.

PMID- 16897256
TI  - Airway evaluation by CT imaging for cri-du-chat syndrome.

PMID- 16897257
TI  - A method for extracting RNA from dormant and germinating Bacillus subtilis strain
      168 endospores.
AB  - RNA was extracted from dormant and germinating Bacillus subtilis 168 spores
      (intact spores and chemically decoated spores) by using rapid rupture followed by
      acid-phenol extraction. Spore germination progress was monitored by assaying
      colony forming ability before and after heat shock and by reading the optical
      density at 600 nm. The purity, yield, and composition of the extracted RNA were
      determined spectrophotometrically from the ratio of absorption at 260 nm to that
      at 280 nm; in a 2100 BioAnalyzer, giving the RNA yield/10(8) spores or cells and
      the distribution pattern of rRNA components. The method reported here for the
      extraction of RNA from dormant spores, as well as during different phases of
      germination and outgrowth, has proven to be fast, efficient and simple to handle.
      RNA of a high purity was obtained from dormant spores and during all phases of
      germination and growth. There was a significant increase in RNA yield during the
      transition from dormant spores to germination and subsequent outgrowth.
      Chemically decoated spores were retarded in germination and outgrowth compared
      with intact spores, and less RNA was extracted; however, the differences were not
      significant. This method for RNA isolation of dormant, germinating, and
      outgrowing bacterial endospores is a valuable prerequisite for gene expression
      studies, especially in studies on the responses of spores to hostile
      environmental conditions.

PMID- 16897258
TI  - Effect of aluminum phosphate on alkaline phosphatase activity of polyurethane
      foam immobilized cyanobacteria.
AB  - The impact of insoluble phosphorus such as aluminum and rock phosphate on
      alkaline phosphatase activity of polyurethane foam immobilized cyanobacteria was
      assessed. Polyurethane foam immobilized Nodularia recorded the highest alkaline
      phosphatase activity of 9.04 (m. mol p-nitrophenol released h(-1) mg(-1) protein)
      in vitro. A higher concentration of aluminum phosphate was recorded a 25%
      reduction in alkaline phosphatase activity, ammonia content, and available
      phosphorus in culture filtrate of polyurethane foam immobilized cyanobacteria. In
      general, immobilized cyanobacteria exhibited a higher alkaline phosphatase
      activity in rock phosphate than aluminum phosphate.

PMID- 16897259
TI  - Evolution of BK virus based on complete genome data.
AB  - The human polyomavirus BK virus (BKV) is ubiquitous in humans, infecting children
      asymptomatically. BKV is the only primate polyomavirus that has subtypes (I-IV)
      distinguishable by immunological reactivity. Nucleotide (nt) variations in a
      major capsid protein (VP1) gene region (designated the epitope region), probably
      responsible for antigenic diversity, have been used to classify BKV isolates into
      subtypes. Here, with all the protein-encoding gene sequences, we attempted to
      elucidate the evolutionary relationships among 28 BKV isolates belonging to
      subtypes I, III, and IV (no isolate belonging to subtype II, a minor one, was
      included). First, using the GTR + Gamma + I model, maximum likelihood trees were
      reconstructed for individual viral genes as well as for concatenated viral genes.
      On the resultant trees, the 28 BKV isolates were consistently divided into three
      clades corresponding to subtypes I, III, and IV, although bootstrap probabilities
      are not always high. Then we used more sophisticated likelihood models, one of
      which takes account of codon structure, to elucidate the phylogenetic
      relationships among BKV subtypes, but the phylogeny of the deep branchings
      remained ambiguous. Furthermore, the possibility of positive selection in the
      evolution of BKV was examined using the nonsynonymous/synonymous rate ratio as a
      measure of selection. An analysis based on entire genes could not detect any
      strong evidence for positive selection, but that based on the epitope region
      identified a few sites potentially under positive selection (these sites were
      among those showing subtype linked polymorphisms).

PMID- 16897260
TI  - Molecular evolution of the puroindoline-a, puroindoline-b, and grain softness
      protein-1 genes in the tribe Triticeae.
AB  - The genome organization of the Hardness locus in the tribe Triticeae constitutes
      an excellent model for studying the mechanisms of evolution that played a role in
      the preservation and potential functional innovations of duplicate genes. Here we
      applied the nonsynonymous-synonymous rate ratio (d ( N )/d ( S ) or omega) to
      measure the selective pressures at the paralogous puroindoline-a (Pina),
      puroindoline-b (Pinb), and grain softness protein-1 (Gsp-1) genes located at this
      locus. Puroindolines represent the molecular-genetic basis of grain texture. In
      addition, the puroindoline gene products have antimicrobial properties with
      potential role in plant defense. We document the complete coding sequences from
      the Triticum/Aegilops taxa, rye and barley including the A, D, C, H, M, N, R, S,
      and U genomes of the Triticeae. Maximum likelihood analyses performed on Bayesian
      phylogenetic trees showed distinct evolutionary patterns among Pina, Pinb, and
      Gsp-1. Positive diversifying selection appeared to drive the evolution of at
      least one of the three genes examined, suggesting that adaptive forces have
      operated at this locus. Results evidenced positive selection (omega > 4) at Pina
      and detected amino acid residues along the mature PIN-a protein with a high
      probability (>95%) of having evolved under adaptation. We hypothesized that
      positive selection at the Pina region is congruent with its role as a plant
      defense gene.

PMID- 16897262
TI  - Usefulness and limitation of manual aspiration immediately after pneumothorax
      complicating interventional radiological procedures with the transthoracic
      approach.
AB  - The goal of this study was to evaluate the efficacy of simple aspiration of air
      from the pleural space to prevent increased pneumothorax and avoid chest tube
      placement in cases of pneumothorax following interventional radiological
      procedures performed under computed tomography fluoroscopic guidance with the
      transthoracic percutaneous approach. While still on the scanner table, 102 cases
      underwent percutaneous manual aspiration of a moderate or large pneumothorax that
      had developed during mediastinal, lung, and transthoracic liver biopsies and
      ablations of lung and hepatic tumors (independent of symptoms). Air was aspirated
      from the pleural space by an 18- or 20-gauge intravenous catheter attached to a
      three-way stopcock and 20- or 50-mL syringe. We evaluated the management of each
      such case during and after manual aspiration. In 87 of the 102 patients (85.3%),
      the pneumothorax had resolved completely on follow-up chest radiographs without
      chest tube placement, but chest tube placement was required in 15 patients.
      Requirement of chest tube insertion significantly increased in parallel with the
      increased volume of aspirated air. When receiver-operating characteristic curves
      were applied retrospectively, the optimal cutoff level of aspirated air on which
      to base a decision to abandon manual aspiration alone and resort to chest tube
      placement was 670 mL. Percutaneous manual aspiration of the pneumothorax
      performed immediately after the procedure might prevent progressive pneumothorax
      and eliminate the need for chest tube placement. However, when the amount of
      aspirated air is large (such as more than 670 mL), chest tube placement should be
      considered.

PMID- 16897261
TI  - Specific selection pressure at the third codon positions: contribution to 10- to
      11-base periodicity in prokaryotic genomes.
AB  - Prokaryotic sequences are responsible for more than just protein coding. There
      are two 10- to 11-base periodical patterns superimposed on the protein coding
      message within the same sequence. Positional auto- and cross-correlation analysis
      of the sequences shows that these two patterns are a short-range counter-phase
      oscillation of AA and TT dinucleotides and a medium-range in-phase oscillation of
      the same dinucleotides, spanning distances of up to approximately 30 and
      approximately 100 bases, respectively. The short-range oscillation is encoded by
      the amino acid sequences themselves, apparently, due to the presence of
      amphipathic alpha-helices in the proteins. The medium-range oscillation, related
      to DNA folding in the cell, is created largely by a special choice of the bases
      in the third positions of the codons. Interestingly, the amino acid sequences do
      contribute to that signal as well. That is, the very amino acid sequences are, to
      some extent, degenerate to serve the same oscillating pattern that is associated
      with the degenerate third codon positions.

PMID- 16897263
TI  - Covered stent-graft treatment of traumatic internal carotid artery
      pseudoaneurysms: a review.
AB  - OBJECTIVE: To review the literature concerning the management with placement of
      covered stent-grafts of traumatic pseudoaneurysms of the extracranial internal
      carotid artery (ICA) resulting from penetrating craniocervical injuries or skull
      base fractures. METHOD: We have reviewed, from the Medline database, all the
      published cases in the English literature since 1990 and we have added a new
      case. RESULTS: We identified 20 patients with traumatic extracranial ICA
      pseudoaneurysms due to penetrating craniocervical injuries or skull base
      fractures who had been treated with covered stent-graft implantation. Many
      discrepancies have been ascertained regarding the anticoagulation therapy. In 3
      patients the ICA was totally occluded in the follow-up period, giving an overall
      occlusion rate 15%. No serious complication was reported as a result of the
      endovascular procedure. CONCLUSION: Preliminary results suggest that placement of
      stent-grafts is a safe and effective method of treating ICA traumatic
      pseudoaneurysms resulting from penetrating craniocervical injuries or skull base
      fractures. The immediate results are satisfactory when the procedure takes place
      with appropriate anticoagulation therapy. The periprocedural morbidity and
      mortality and the early patency are also acceptable. A surveillance program with
      appropriate interventions to manage restenosis may improve the long-term patency.

PMID- 16897264
TI  - Acute iliac artery rupture: endovascular treatment.
AB  - The authors present 7 patients who suffered iliac artery rupture over a 2 year
      period. In 5 patients, the rupture was iatrogenic: 4 cases were secondary to
      balloon angioplasty for iliac artery stenosis and 1 occurred during coronary
      angioplasty. In the last 2 patients, the rupture was secondary to iliac artery
      mycotic aneurysm. Direct placement of a stent-graft was performed in all cases,
      which was dilated until extravasation was controlled. Placement of the stent
      graft was successful in all the cases, without any complications. The techniques
      used, results, and mid-term follow-up are presented. In conclusion, endovascular
      placement of a stent-graft is a quick, minimally invasive, efficient, and safe
      method for emergency treatment of acute iliac artery rupture, with satisfactory
      short- and mid-term results.

PMID- 16897265
TI  - Long-term placement of subcutaneous Rusch-type stents for double biliary stenosis
      in a living-donor liver transplant recipient.
AB  - Biliary reconstruction continues to be a major source of morbidity following
      liver transplantation. The spectrum of biliary complications is evolving due to
      the increasing number of split-liver and living-donor liver transplantation,
      which are even associated with a higher incidence of biliary complications. Bile
      duct strictures are the most common cause of late biliary complications and
      account for up to 40% of all biliary complications. Optimal therapy for
      posttransplantation anastomotic biliary strictures remains uncertain and requires
      a multidisciplinary approach. We report the case of a 54-year-old Caucasian male
      affected by hepatocarcinoma and hepatitis C-related cirrhosis who underwent right
      lobe living-donor liver transplantation from his son complicated by double
      anastomotic stenosis of the main right hepatic duct and of an accessory biliary
      duct draining segments 6 and 7 of the graft that was successfully treated by
      percutaneous transhepatic cholangiography with long-term subcutaneous placement
      of two internal Rusch-type biliary stents.

PMID- 16897266
TI  - Utility of stent-grafts in treatment of porto-biliary fistula.
AB  - A porto-biliary fistula causing hemobilia is a known complication of percutaneous
      transhepatic biliary drainage (PTBD). We present two patients with hemobilia
      secondary to porto-biliary fistula, treated successfully by percutaneous
      placement of stent-grafts. In one case, the stent-graft was placed in the bile
      duct, and in the other case, it was placed in the intrahepatic portal vein
      branch. Hemobilia stopped and there were no complications except a small area of
      hepatic infarction, distal to the stent-graft in the portal vein.

PMID- 16897267
TI  - Comparison of contrast-enhanced ultrasound and computed tomography in classifying
      endoleaks after endovascular treatment of abdominal aorta aneurysms: preliminary
      experience.
AB  - The purpose of the study was to assess the effectiveness of contrast-enhanced
      ultrasonography (CEUS) in endoleak classification after endovascular treatment of
      an abdominal aortic aneurysm compared to computed tomography angiography (CTA).
      From May 2001 to April 2003, 10 patients with endoleaks already detected by CTA
      underwent CEUS with Sonovue to confirm the CTA classification or to reclassify
      the endoleak. In three conflicting cases, the patients were also studied with
      conventional angiography. CEUS confirmed the CTA classification in seven cases
      (type II endoleaks). Two CTA type III endoleaks were classified as type II using
      CEUS and one CTA type II endoleak was classified as type I by CEUS. Regarding the
      cases with discordant classification, conventional angiography confirmed the
      ultrasound classification. Additionally, CEUS documented the origin of type II
      endoleaks in all cases. After CEUS reclassification of endoleaks, a significant
      change in patient management occurred in three cases. CEUS allows a better
      attribution of the origin of the endoleak, as it shows the flow in real time.
      CEUS is more specific than CTA in endoleak classification and gives more accurate
      information in therapeutic planning.

PMID- 16897269
TI  - Bilateral persistent sciatic artery aneurysm discovered by atypical sciatica: a
      case report.
AB  - We report a case of a bilateral persistent sciatic artery aneurysm, diagnosed by
      atypical sciatica on computed tomography and magnetic resonance imaging. The
      different variants, the revealing features, and possible treatment are discussed.

PMID- 16897268
TI  - Volume changes of experimental carotid sidewall aneurysms due to embolization
      with liquid embolic agents: a multidetector CT angiography study.
AB  - Iodine-containing polyvinyl alcohol polymer (I-PVAL) is a novel precipitating
      liquid embolic that allows for artifact-free evaluation of CT angiography (CTA).
      As accurate aneurysm volumetry can be performed with multidetector CTA, we
      determined volumes of experimental aneurysms before, immediately after, and 4
      weeks after embolization of 14 porcine experimental carotid sidewall aneurysms
      with this liquid embolic. An automated three-dimensional software measurement
      tool was used for volumetric analysis of volume-rendering CTA data. Furthermore,
      intra-aneurysmal pressure changes during liquid embolization were measured in
      four silicone aneurysms and potential polymer volume changes within 4 weeks were
      assessed in vitro. Liquid embolic injection was performed during temporary
      balloon occlusion of the aneurysm neck, resulting in a mean occlusion rate of
      98.3%. Aneurysms enlarged significantly during embolization by 61.1 +/- 28.9%,
      whereas a significant shrinkage of 5.6 +/- 2.7% was observed within the follow-up
      period. Histologic analysis revealed an inflammatory foreign body reaction with
      partial polymer degradation. In silicone aneurysm models, intra-aneurysmal
      pressure remained unchanged during liquid embolic injection, whereas balloon
      inflation resulted in a mean pressure increase of 31.2 +/- 0.7%. No polymer
      shrinkage was observed in vitro. The aneurysm enlargement noted was presumably
      due to pressure elevation after balloon inflation, which resulted in dilatation
      of the weak venous wall of the newly constructed aneurysm--another shortcoming of
      this experimental aneurysm model. The volume decrease after 4 weeks expressed
      partial polymer degradation.

PMID- 16897270
TI  - Hospital volume and inpatient mortality after cancer-related gastrointestinal
      resections: the experience of an Asian country.
AB  - BACKGROUND: Using 4-year nationwide population-based data for Taiwan, this study
      compared in-hospital surgical mortality rates with hospital volume for five
      cancer-related gastrointestinal resections. METHODS: The study sample was drawn
      from the Taiwan National Health Insurance Research Database. A total of 34,715
      patients, each of whom had undergone a cancer-related colectomy, gastrectomy,
      esophagectomy, pancreatic resection, or liver lobectomy between 2000 and 2003,
      were selected as the study sample. The outcome measure was in-hospital mortality.
      The study sample was categorized into five patient groups for each procedure, and
      logistic regression analyses were performed for each procedure after adjustment
      for hospital and patient characteristics to assess the independent association
      between hospital volume and in-hospital mortality. RESULTS: The adjusted odds
      ratios showed a steady decline in mortality rates for colectomy, gastrectomy,
      esophagectomy, and liver lobectomy with increasing hospital volume. The adjusted
      mortality odds for these four procedures in very-high-volume hospitals, relative
      to very-low-volume hospitals, ranged from .65 to .05. As regards pancreatic
      resection, after adjustment for patient, clinical, and hospital factors, no
      statistically significant association was discernible between hospital volume and
      the likelihood of mortality. CONCLUSIONS: After adjustment for hospital and
      physician characteristics, in four of the five procedures, patients treated at
      higher-volume hospitals had lower in-hospital mortality rates than those treated
      at lower-volume hospitals. Our findings confirm, for the most part, the
      hypothesis that better outcomes are associated with higher-volume hospitals.

PMID- 16897271
TI  - Postresectional adjuvant intraportal chemotherapy in patients with hepatocellular
      carcinoma: a case-control study.
AB  - BACKGROUND: The postresectional tumor recurrence rate is high in patients with
      hepatocellular carcinoma (HCC). Tumor portal venous invasion is the most
      important factor related to recurrence. Adjuvant intraportal infusion
      chemotherapy (IPIC) was used in HCC patients to improve the outcomes. METHODS:
      Between June 1998 and May 1999, 28 HCC patients (IPIC group) underwent
      postresectional IPIC daily for 2 days with 5-fluorouracil (650 mg/m(2)),
      leucovorin (45 mg/m(2)), doxorubicin (10 mg/m(2)), and cisplatin (20 mg/m(2)).
      Treatment was repeated every 3 weeks for six cycles. Patient outcomes were
      compared with those of 66 matched HCC patients (control group) who underwent
      hepatectomy without adjuvant therapy. RESULTS: The IPIC group received an average
      of 5.2 cycles of chemotherapy, starting 5 to 24 days after surgery. The most
      frequent IPIC-related adverse events were upper abdominal pain, vomiting, and
      myelosuppression. Five-year disease-free and overall survival rates for the IPIC
      group were 44.6% and 60.7%, respectively. Subgroup analysis of patients with
      tumor-node-metastasis stage I and II disease identified significantly lower
      recurrence rates for the IPIC group (33.3%) than the control group (65.0%; P =
      .025). For patients with stage I and II disease, 5-year disease-free and overall
      survival rates for the IPIC group (70.6% and 83.3%, respectively) were
      significantly higher than those of the control group (33.4% and 46.9%,
      respectively; P < .05). Patients with stage III disease do not benefit from IPIC.
      CONCLUSIONS: Postoperative IPIC benefits HCC patients with tumor-node-metastasis
      stage I and II disease. The survival advantages demonstrated justify a selection
      of patients for future trials.

PMID- 16897272
TI  - Surgical adjuvant therapy for colorectal cancer: current approaches and future
      directions.
AB  - Colon cancer is the fourth most common cancer worldwide. The role of systemic
      adjuvant chemotherapy in colorectal cancer patients with lymph node involvement
      has been established in a large number of clinical trials. However, its role in
      stage II colorectal cancer is less well established. 5-Fluorouracil has been the
      mainstay of therapy for the last four decades. With the development of novel
      chemotherapy and biological agents, we have entered into a new era for the
      treatment of colorectal cancer. The combination of adjuvant 5-fluorouracil,
      leucovorin, and oxaliplatin has been shown to significantly improve disease-free
      survival and is now considered the standard of care for completely resected colon
      cancer in healthy patients. For rectal cancer patients with locally advanced
      tumors, neoadjuvant chemoradiation followed by adjuvant chemotherapy after
      surgery is the mainstay of treatment. The availability of oral chemotherapy
      agents has helped with the ease of administration and avoidance of indwelling
      catheters. A number of national clinical trials are under way to determine the
      role of targeted agents in combination with chemotherapy. The goal is to develop
      a regimen that would improve survival without excessive toxicity while
      maintaining quality of life. Patients should be encouraged to participate in
      clinical trials whenever feasible. Despite the advances, many patients will
      develop recurrent disease. It is of utmost importance to develop molecular
      markers that could predict which patients are at high risk for disease
      recurrence. Clinical trials are under way to address this issue. Thus, it will be
      advantageous to be able to tailor therapy individually, according to the risk of
      recurrence.

PMID- 16897273
TI  - Clinical Experience With Mammary Ductoscopy.
AB  - BACKGROUND: Most breast cancers begin in the ductal epithelium with normal cells
      and progress to atypia and finally to carcinoma. Mammary ductoscopy enables one
      to directly visualize and sample the ductal epithelium and, therefore, identify
      early changes cytologically. This article describes our initial experience with
      mammary ductoscopy at Beth Israel Medical Center. METHODS: A prospective review
      of all patients who underwent ductoscopy at Beth Israel Medical Center from
      November 2001 to February 2004 was performed. The indications for ductoscopy were
      a persistent nipple discharge, high-risk status, or intraoperative margin
      assessment in patients undergoing lumpectomy. RESULTS: Seventy-four patients
      underwent ductoscopic evaluation of 88 ducts. Of the 32 patients who underwent
      office ductoscopy, 15 were high risk, and 17 had spontaneous nipple discharge.
      Spontaneous nipple discharge was the indication for ductoscopy in 40 of 42
      intraoperative procedures. The remaining two patients underwent ductoscopy for
      margin assessment during breast conservation, and final pathologic analysis
      revealed negative margins. Thirty-eight of the 40 patients who had spontaneous
      nipple discharge had abnormal findings during ductoscopy and therefore underwent
      ductoscopically guided duct excision. Carcinoma was the final diagnosis in 5
      (8.8%) of the 57 patients who were scoped for nipple discharge. CONCLUSIONS:
      Mammary ductoscopy is a potentially useful tool in the evaluation of patients
      with spontaneous nipple discharge. This is a well-tolerated office procedure with
      minimal risks and complications. Mammary ductoscopy may have a role in the
      assessment of high-risk women. Further research is necessary to confirm these
      potential applications.

PMID- 16897275
TI  - Ultrasonography of the pancreas. 1. Conventional imaging.
AB  - Ultrasound imaging has made significant advances in recent years and plays an
      important role in the detection, characterization and staging of pancreatic
      diseases. Conventional ultrasonography (US) is a noninvasive imaging modality,
      which continues to be the first diagnostic step in the evaluation of the
      pancreas. Over its various decades of application, US have detected pancreatic
      pathology of great diversity. This article reviews the wide utility of US and the
      many examinations techniques, such as filling the stomach with water, changing
      the patient's position or suspending inspiration or expiration, allowing us to
      visualize all portions of the pancreas in a high percentage of patients.

PMID- 16897274
TI  - Effects of copper, cadmium, and zinc on the hatching success of brine shrimp
      (Artemia franciscana).
AB  - Previous studies indicate that the hatching success of brine shrimp (Artemia
      franciscana) cysts is surprisingly sensitive to ambient metal concentrations.
      These studies estimated median effective concentrations (EC50s) of 7, 5, and 28
      microg l-1 for Cd, Cu, and Zn, suggesting that the hatching end point for A.
      franciscana is the most sensitive tested to date for Cd and Zn in saline
      environments and comparable in sensitivity with the most sensitive tested to date
      for Cu. Furthermore, these data suggest that brine shrimp are at significant risk
      from Cu and Zn in Great Salt Lake (GSL), UT, where ambient concentrations as high
      as 10 and 14 microg l-1, respectively, have been measured. Given that brine
      shrimp appear to be successfully reproducing in GSL, we hypothesized that these
      toxicity values were either biased low as a result of an artifact of the test
      method used or that site-specific water-quality conditions in the lake had
      decreased metal bioavailability such that brine shrimp could successfully
      reproduce. To test these hypotheses, we initiated a step-wise series of
      experiments. First we investigated the effects of pretreatment of brine shrimp
      cysts with antibiotics on brine shrimp sensitivity to metals because previous
      investigators as part of their test methods have used antibiotics. Next we
      considered the effect of ionic composition of the artificial test media on
      sensitivity. Finally, we evaluated the effects of the site-specific water quality
      of the GSL on metal bioavailability and toxicity. Results indicate that
      pretreatment of cysts with antibiotics had no effect on sensitivity. However, we
      were unable to repeat the previous values for Cd and Zn, obtaining EC50s of
      11,859 and 289 microg l-1 for Cd and Zn, respectively. For Cu, however, we
      estimated an EC50 of 12 microg l-1, so we conducted further testing on the
      artificial media, adjusting the media composition to better reflect the Ca2+ and
      HCO3- concentration of normal seawater. This increased the EC50 to 28 microg l-1.
      Finally we evaluated the toxicity of Cu in GSL water and obtained an EC50 of 68
      microg l-1, suggesting that the increased dissolved organic carbon in GSL has a
      significant protective effect. Overall, the results of this study suggest that
      brine shrimp hatching success is not particularly sensitive to Cd and Zn, but it
      is sensitive to Cu. However, site-specific water-quality conditions ensure that
      brine shrimp cyst hatching success is not significantly affected by any of these
      metals at the normal background concentrations that occur in GSL (<15 microg l
      1).

PMID- 16897276
TI  - Acute cholecystitis due to strangulation of a floating gallbladder by the lesser
      omentum.
AB  - We report a unique case of acute cholecystitis due to strangulation of a floating
      gallbladder by the lesser omentum, which could be detected by abdominal
      ultrasonography. We believe this case to be the first case of reported
      literatures in English.

PMID- 16897278
TI  - Cross-sectional imaging of nodal metastases in the abdomen and pelvis.
AB  - Accurate nodal staging is important for the management of patients with abdominal
      and pelvic malignancies. Local and nodal staging using cross-sectional imaging
      can influence treatment planning. The measurement of nodal size is still the most
      widely used criteria for discriminating between benign and malignant nodes.
      However, knowledge of the pathways of nodal spread, the treatment history, and
      careful analysis of nodal characteristics can improve nodal assessment. An
      appreciation of normal structures that may simulate nodal disease is also
      important. The potential for further improving nodal staging accuracy by positron
      emission tomography and magnetic resonance lymphography is discussed.

PMID- 16897279
TI  - Nodal staging in rectal cancer.
AB  - Rectal cancer is common and nodal disease is an independent adverse prognostic
      factor for patient survival. Accurate demonstration of the presence and location
      of nodal disease preoperatively may influence management strategies. In this
      article we review the pathways of nodal spread in rectal cancer and assessment of
      nodal disease using sonography, CT, and MRI. The use of morphological criteria
      instead of size criteria has been shown to improve nodal staging by MRI. The
      potential role of magnetic resonance lymphography and PET imaging in further
      improving nodal staging accuracy is discussed.

PMID- 16897280
TI  - Aneurysm of the inferior vena cava: case report.
AB  - Venous aneurysms are uncommon. Despite their infrequency, venous aneurysms can
      present with significant clinical complications such as thrombosis, pulmonary
      embolism, and death. In this report, we present the case of a thrombosed inferior
      vena cava aneurysm discovered in a 16-year-old male who had deep vein thrombosis
      of the right lower extremity. Thrombosis of the inferior vena cava is uncommon in
      the pediatric population. Therefore, congenital abnormalities such as an inferior
      vena cava aneurysm should be considered when evaluating pediatric patients who
      present with deep vein thrombosis.

PMID- 16897281
TI  - How to teach an old dog new tricks and how to teach a new dog old tricks:
      bridging the generation gap to push the envelope of advanced laparoscopy.

PMID- 16897282
TI  - Thoracoscopic and laparoscopic oesophagectomy improves the quality of extended
      lymphadenectomy.
AB  - BACKGROUND: Oesophagectomy with extended lymphadenectomy carries considerable
      morbidity due to parietal trauma. It is also technically extremely demanding
      because the difficult access even through a large thoracotomy requires the use of
      long instruments to reach the deepest recess in the chest cavity. Since the first
      thoracoscopic oesophagectomy reported by Cuschieri et al. [1] in 1992, different
      minimally invasive approaches have been proposed [2-12]. The aim of this video is
      to show the accurate and relative ease of an entirely thoracoscopic and
      laparoscopic oesophagectomy with an extended lymph node dissection of mediastinum
      in prone position (thoracoscopically) and celiac trunk (laparoscopically).
      METHODS: Oesophagectomy by thoracoscopy, laparoscopy and cervicotomy was proposed
      in a 63-year-old man with a lower third oesophageal cancer. General anaesthesia
      was performed with a double-lumen endotracheal tube and the patient was placed in
      prone position. Surgeons were positioned at the right side of the patient. Only
      three trocars were needed. A 10 mm 30-degree angled scope was inserted in the 7th
      intercostal space on the posterior axillary line and the remaining two 5 mm
      trocars were inserted in the 5th and 9th intercostal spaces on the posterior
      axillary line. Prone position allows an excellent visibility of the operative
      field even in an only partially deflated lung. In order to achieve a good
      exposure, transitory pneumothorax with CO2 (14 mmHg) was performed. The
      mediastinal pleura overlying the oesophagus was incised and the arch of azygos
      vein was isolated, ligated and divided. The oesophagus was circumferentially
      mobilized from the thoracic inlet down to oesophageal hiatus. Para oesophageal
      and subcarinal lymph nodes were dissected so as to remain in block with the
      surgical specimen. A 28 F chest tube was inserted in the 8th intercostal space on
      the anterior axillary line. In the second stage the patient was placed in supine
      position and pneumoperitoneum was established. Five trocars were placed along an
      ideal semicircular line, with the concavity facing the subcostal margin and a 30
      degree angled laparoscope was used. The lesser omentum was widely opened up the
      right pillar of the hiatus. Mobilization of the greater curvature of the stomach
      was performed preserving the right gastroepiploic artery. A wide Kocher maneuver
      was performed. Celiac lymphadenectomy started with skeletonization of the hepatic
      artery until the root of left gastric artery was reached. This artery and the
      left gastric vein were dissected, clipped and sectioned. All fatty tissue and
      lymph nodes along hepatic artery, left gastric artery and celiac trunk were
      resected in block with the surgical specimen. Multiple applications of a linear
      endoscopic stapler were used to create the gastric tube. Finally the distal
      oesophagus was dissected, until the thoracoscopic dissection field was joined. In
      the third stage a left lateral cervicotomy was performed and the cervical
      oesophagus was dissected down to the thoracoscopic dissection plane. Oesophagus
      and stomach were delivered through the cervical incision and an oesophagogastric
      anastomosis was created by a linear stapler technique. Cervical and abdominal
      drainages were installed. RESULTS: The total operative time was 271 minutes
      (thoracoscopy: 106 minutes, laparoscopy 120 minutes and cervicotomy 45 minutes)
      and blood loss was about 100 ml. Histological examination demonstrated a squamous
      cell carcinoma. Both margins of resection were free of tumour and 29 lymph nodes
      were retrieved. The final stage was IIA (pT3N0Mx). CONCLUSIONS: Thoracoscopic and
      laparoscopic oesophagectomy with extended lymphadenectomy is technically feasible
      and safe. Thoracoscopic oesophagectomy in prone position improves the quality of
      dissection because: The oesophagus and aorto-pulmonary window are reached under
      excellent visibility, despite a partially deflated lung, which because of gravity
      will always remain out of harm's way. For the same reason small to moderate
      bleeding will not obscure the operative field. Dissection with the long
      endoscopic instruments is more accurate due to the support provided by the
      entrance site at the parietal level and the ergonomic position of surgeon. This
      article contains a supplementary video.

PMID- 16897284
TI  - Robotic-assisted laparoscopic low anterior resection with total mesorectal
      excision for rectal cancer.
AB  - BACKGROUND: With advanced stereoscopic vision, lack of tremor, and the ability to
      rotate the instruments surgeons find that robotic systems are ideal laparoscopic
      tools. Because of its high operating cost, however, robotic surgery should be
      reserved to procedures in which the technology can be of maximum benefit, usually
      when precise dissections in confined spaces are required. Because conventional
      laparoscopic total mesorectal excision is a challenging procedure, we have sought
      to assess the utility of the DaVinci robotic system in laparoscopic low anterior
      resections for cancer of the rectum. METHODS: Between November 2004 and May 2005
      robotic-assisted low anterior resection with total mesorectal excision was
      performed on six consecutive patients with rectal cancer. These cases were
      compared with six consecutive low anterior resections performed with conventional
      laparoscopic techniques by the same surgeon. RESULTS: There were no conversions
      in either group. Operative and pathological data, complications, and hospital
      stay were similar in the two groups. Robotic operations appeared to cause less
      strain for the surgeon. CONCLUSIONS: Robotic-assisted laparoscopic low anterior
      resection for rectal cancer is feasible in experienced hands. This technique may
      facilitate minimally invasive radical rectal surgery.

PMID- 16897283
TI  - Percutaneous treatment of univesicular versus multivesicular hepatic hydatid
      cysts.
AB  - BACKGROUND: Percutaneous drainage has been used successfully to treat hepatic
      hydatid cysts. This study aimed to analyze the results of this method in the
      treatment of univesicular and multivesicular hepatic hydatid cysts. METHODS:
      Ultrasound-guided percutaneous drainage was used to treat 72 patients (44 women
      and 28 men; average age, 46.8 +/- 17.7 years) with hepatic hydatidosis. Of these
      72 patients, 57 had one cyst, 7 had two cysts, and 8 had three cysts. Albendazole
      (10 mg per kg of body weight daily for 8 weeks) was administered to all the
      patients. Serial assessments included clinical and biochemical examinations,
      ultrasonography, and serologic tests for echinococcal antibody titers. RESULTS:
      During the follow-up period, the mean cyst diameter decreased from 83.3 +/- 38.6
      mm to 11.1 +/- 16.0 mm (p < 0.001) in the multivesicular group (27 cysts) and
      from 65.5 +/- 27.5 to 5.9 +/- 13.0 mm (p < 0.001) in the univesicular group (68
      cysts). The final cyst diameter did not differ significantly between the two
      groups (p = 0.1). The findings showed that 81% of the cysts in the univesicular
      group and 63% in the multivesicular group disappeared (p = 0.12). The mean
      hospital stay was 4.8 +/- 2.9 days in the univesicular group and 6.1 +/- 4.7 days
      in the multivesicular group (p < 0.001). After an initial rise, the echinococcal
      antibody titers fell progressively, and at the last follow-up evaluation were
      negative (<1:160) for 43 patients (94%) in the univesicular group and 19 patients
      (73%) in the multivesicular group (p = 0.03). Mild nonfatal complications were
      experienced by 24 patients (33%). CONCLUSIONS: Percutaneous drainage combined
      with albendazole therapy is an effective and safe method for managing hydatid
      cysts of the liver that requires a short hospital stay. Disappearance of the
      cysts depends on cyst size. Multivesicular cysts have a more complicated course,
      a slower disappearance, and a higher incidence of positive echinococcal-antibody
      titers. Abscess formed after the procedure can be treated successfully by
      percutaneous drainage.

PMID- 16897285
TI  - Long-term results of endoscopic stent in the management of blunt major pancreatic
      duct injury.
AB  - BACKGROUND: Pancreatic stents can be used to treat a variety of acute and chronic
      pancreatic lesions. Sporadic successful trials in trauma patients have been
      reported. To our knowledge, however, a series with long-term follow-up has not
      previously been reported. We treated six patients in a 6-year period and report
      the long-term results. METHODS: From February 1999 to February 2005, six blunt
      trauma patients with major pancreatic duct disruption were treated with
      pancreatic duct stent at a single trauma center. Assessment of injury severity
      and diagnosis were based on abdominal computed tomography (CT) and proved by
      endoscopic retrograde pancreatography (ERP), with chart review used to establish
      mechanism of injury, timing of ERP, and stent placement, as well as the long-term
      outcome. RESULTS: Three of the six injuries were classified AAST grade III and
      three were grade IV; the interval to ERP with stent placement ranged from 8 hours
      to 22 days after the injury. One patient developed sepsis and died. One patient's
      stent could be removed early (52 days post-stenting) with mild ductal stricture,
      whereas the other four were complicated by severe ductal stricture that required
      repeated and prolonged stenting treatment. Removal of the stents was only
      possible in three of these four cases (at 12, 19, and 39 months, respectively),
      with stent dislodgment in the pancreatic duct occurring in another. CONCLUSIONS:
      Stent therapy may avoid surgery in the acute trauma stage, and may be preserved
      as another choice for acute grade IV pancreatic injury. However, variant outcome
      and long-term ductal stricture reveal that the role of pancreatic duct stent is
      uncertain and may not be suitable for acute grade III pancreatic injury. However,
      it needs more clinical data to define the value in the acute blunt pancreatic
      duct injury.

PMID- 16897287
TI  - Laparoscopic incisional hernia repair. A new mesh fixation method without
      stapling.
AB  - BACKGROUND: Recent advances in laparoscopic surgery have made various abdominal
      surgeries possible. To avoid wound infection, mesh repair of abdominal incisional
      hernias is performed laparoscopically. Here we present a new procedure to fix
      mesh to the abdominal wall. SURGICAL TECHNIQUE: Four anchoring sutures are made
      using a suture-grasping device; the additional transabdominal sutures are then
      made with a modified double-needle device. Additional circumferential fixation
      with tacks is not necessary. CONCLUSIONS: This new mesh fixation method involves
      simple suturing techniques and is less time consuming than the conventional
      procedure.

PMID- 16897286
TI  - Tannenbaum and metal stents in the palliative treatment of malignant distal bile
      duct obstruction: a comparative study of patency and cost effectiveness.
AB  - BACKGROUND: Stent clogging is the major limitation of palliative treatment for
      malignant biliary obstruction. Metal stents have much better patency than plastic
      stents, but are more expensive. Preliminary data suggest that the recently
      designed plastic (Tannenbaum) stent has better duration of patency than the
      polyethylene stent. This study aimed to compare the efficacy and cost
      effectiveness between the Tannenbaum stent without side holes and the uncovered
      metal stent for patients with malignant distal common bile duct obstruction.
      METHODS: In this study, 47 patients (median age, 73 years, range, 56-86 years)
      with inoperable malignant distal common bile duct strictures were prospectively
      randomized to receive either a Tannenbaum stent (n = 24) or an uncovered self
      expandable metal stent (n = 23). The patients were clinically evaluated, and
      biochemical tests were analyzed if necessary until their death or surgery for
      gastric outlet obstruction. Cumulative first stent patency and patient survival
      were compared between the two groups. Cost-effectiveness analysis also was
      performed for the two study groups. RESULTS: The two groups were comparable in
      terms of age, gender, and diagnosis. The median first stent patency was longer in
      the metal group than in the Tannenbaum stent group (255 vs 123.5 days; p =
      0.002). There was no significant difference in survival between the two groups.
      The total cost associated with the Tannenbaum stents was lower than for the metal
      stents (17,700 vs 30,100 euros; p = 0.001), especially for patients with liver
      metastases (3,000 vs 6,900 euros; p < 0.001). CONCLUSIONS: Metal stent placement
      is an effective treatment for inoperable malignant distal common bile duct
      obstruction, but Tannenbaum stent placement is a cost-saving strategy, as
      compared with metal stent placement, especially for patients with liver
      metastases and expected short survival time.

PMID- 16897288
TI  - Methods and mechanisms for contact feedback in a robot-assisted minimally
      invasive environment.
AB  - Providing a surgeon with information regarding contacts made between instruments
      and tissue during robot-assisted interventions can improve task efficiency and
      reliability. In this report, different methods for feedback of such information
      to the surgeon are discussed. It is hypothesized that various methods of contact
      feedback have the potential to enhance performance in a robot-assisted minimally
      invasive environment. To verify the hypothesis, novel mechanisms needed for
      incorporating contact feedback were designed, including a surgeon-robot interface
      with full force feedback capabilities and a surgical end-effector with full force
      sensing capabilities, that are suitable for minimally invasive applications.
      These two mechanisms were used to form a robotic "master-slave" test bed for
      studying the effect of contact feedback on the system and user performance. Using
      the master-slave system, experiments for surgical tasks involving soft tissue
      palpation were conducted. The performance of the master-slave system was
      validated in terms of criteria that assess the accurate transmission of task
      related information to the surgeon, which is critical in the context of soft
      tissue surgical applications. Moreover, using a set of experiments involving
      human subjects, the performance of several users in carrying out the task was
      compared among different methods of contact feedback.

PMID- 16897289
TI  - Impact of different pressures and exposure times of a simulated carbon dioxide
      pneumoperitoneum environment on proliferation and apoptosis of human ovarian
      cancer cell lines.
AB  - BACKGROUND: This study aimed too evaluate the proliferation and apoptosis of
      human ovarian cancer cell lines HO8910 and SKOV3 after exposure to a simulated
      laparoscopic carbon dioxide (CO2) pneumoperitoneum environment at different
      pressures and lengths of exposure time. METHODS: The effects of the simulated
      laparoscopic CO2 pneumoperitoneum environment at different CO2 pressures (0-16
      mmHg) and exposure times (1-4 h) on tumor cell growth and apoptosis were assessed
      by 3-[4,5-Dimethylthiazol]-2; 5-diphenyltetrazolium bromide (MTT) chromometry and
      proliferative index (PI) staining or Annexin V and PI double-staining flow
      cytometry. Cells cultured in a standard environment were used as the control
      group. RESULTS: In this study, HO8910 cell growth tended to slow down with the
      increase in CO2 pressure and exposure time. A significantly lower PI was observed
      at 72 h of culture after exposure to both 8 and 16 mmHg of pressure, as compared
      with the control and 0 mmHg pressure group (p < 0.05). The PI of SKOV3 cells
      tended to decline after exposure. Significantly lower PI was observed in the
      group with exposure to 16 mmHg for 4 h over a 72-h period, as compared with the
      control groups exposed to 0 mmHg (p < 0.05). The inhibition of cell growth was
      associated with an increase in the proportion of cells at stage G1. The apoptotic
      index and the percentage of apoptotic cells tended to increase with an increase
      in pressure and a prolonged time of exposure. CONCLUSIONS: The results suggest
      inhibited cell proliferation and increased cell apoptosis of human ovarian cancer
      cells were positively related to CO2 pressure and exposure time.

PMID- 16897290
TI  - Intraoperative magnetic resonance imaging for ablation of hepatic tumors.
AB  - BACKGROUND: The most significant rise in the use of hepatic ablation has come
      from image-guided techniques with both computed tomography (CT) and ultrasound
      (US). The recent development of open-configuration magnetic resonance scanners
      has opened up an entire new area of image-guided surgical and interventional
      procedures. Thus the aim of this study was to evaluate the use of intraoperative
      MRI (iMRI) ablation of hepatic tumors performed by surgeons. METHOD: Percutaneous
      iMRI hepatic ablation was performed from January 2003 to February 2005 for
      control of either primary or secondary hepatic disease. RESULTS: Eighteen hepatic
      ablations were performed on 11 patients with a median age of 71 (range: 51-81)
      years for metastatic colorectal cancer (n = 6), hepatocellular cancer (n = 2),
      cholangiocarcinoma (n = 2), and metastatic neuroendocrine (n = 1). Median
      hospital stay was 1 day, with complications occurring in 2 patients. After a
      median follow up of 18 months, there have been no local ablation recurrences, 5
      patients are free of disease, 4 are alive with disease, 1 has died of disease,
      and 1 has died of other causes. CONCLUSIONS: Image-guided hepatic ablations
      represent a useful technique in managing hepatic tumors. Intraoperative MRI
      represents a new technique with initial success that has been limited to European
      centers. Further evaluation in U.S. centers has demonstrated iMRI to be useful
      for certain hepatic tumors that cannot be adequately visualized by US or CT.

PMID- 16897291
TI  - Placement of 0.5% bupivacaine-soaked Surgicel in the gallbladder bed is effective
      for pain after laparoscopic cholecystectomy.
AB  - BACKGROUND: This study aimed to determine the character of pain after
      laparoscopic cholecystectomy and its relief with 0.5% bupivacaine-soaked Surgicel
      placed in the gallbladder bed. METHODS: For this study, 60 patients with chronic
      cholecystitis were divided into four groups of 15 each: group A (bupivacaine
      soaked Surgicel kept in gallbladder bed), group B (bupivacaine infiltrated at
      trocar sites), group C (bupivacaine infiltrated into the gallbladder bed and at
      trocar sites, and group D (normal saline in the gallbladder bed and at trocar
      sites). Postoperatively, the character of pain was noted, and its relief was
      assessed with visual analog scale (VAS) scoring. RESULTS: The findings showed
      that 78.33% of the patients had visceral pain, 70% experienced parietal, and
      23.33% reported shoulder pain after laparoscopic cholecystectomy. The visceral
      pain was significantly less in the group A patients than in the control subjects
      (p < 0.05), and none of them experienced shoulder pain. The mean VAS score at 4,
      8, and, 24 h in the group A patients also was less than in control group D: 26.37
      +/- 16.24 versus 38.30 +/- 9.51, 23.23 +/- 14.28 versus 33.73 +/- 7.96, and 18.36
      +/- 13.00 versus 28.60 +/- 9.42, respectively. Trocar-site infiltration alone was
      not effective in relieving the parietal pain. CONCLUSION: Visceral pain is
      prominent after laparoscopic cholecystectomy and can be effectively controlled by
      0.5% bupivacaine-soaked Surgicel in the gallbladder bed alone. Trocar-site
      infiltration alone is ineffective.

PMID- 16897292
TI  - Endoscopic retrograde cholangiopancreatography and gastroduodenoscopy after Roux
      en-Y gastric bypass.
AB  - BACKGROUND: The use of Roux-en-Y gastric bypass (RYGB) for morbid obesity has
      raised concern that subsequent endoscopic evaluation of the gastric remnant and
      duodenum is difficult. By gaining percutaneous access to the gastric remnant,
      however, both gastroduodenoscopy and endoscopic retrograde
      cholangiopancreatography (ERCP) can be performed easily. This report describes
      the results of a novel technique for performing "transgastrostomy"
      gastroduodenoscopy and ERCP. METHODS: Six patients with a RYGB for morbid obesity
      underwent transgastric remnant endoscopic evaluations. If a gastric remnant tube
      had not been placed during prior surgery, one was placed percutaneously by an
      interventional radiologist. The tube tract then was dilated to either 20- or 24
      Fr. At the time of endoscopy, the gastrostomy tube was removed and the skin
      anesthetized. Then either a pediatric duodenoscope (outer diameter, 7.5 mm) or a
      slim gastroscope (outer diameter, 5.9 mm) was inserted through the gastrostomy
      tube tract. RESULTS: Percutaneous gastroduodenoscopy was successfully performed
      for all six patients. The findings included two patients with prepyloric ulcers
      identified and assessed with a biopsy, one patient with intestinal metaplasia and
      a benign gastric polyp, and three patients with a normal gastric remnant and
      duodenum. A nonstrictured enteroenterostomy was noted in one of the three
      patients with a normal endoscopic evaluation. Percutaneous transgastrostomy ERCP
      was performed for three of the six patients who underwent gastroduodenoscopy. The
      findings included one patient who had papillary fibrosis treated with a
      sphincterotomy, a second patient with a normal biliary tree, and a third patient
      with a normal pancreatic duct. Selective cannulation of the common bile duct was
      not successful in the third patient. CONCLUSION: The transgastrostomy endoscopic
      route ensures access to the excluded stomach and proximal small bowel after RYGB.
      This route is safe and effective, allowing the use of a duodenoscope to improve
      the cannulation success rate for ERCPs in this patient population.

PMID- 16897293
TI  - Videolaparoscopic appendectomy: the current outlook.
AB  - BACKGROUND: Mini-invasive techniques have revolutionized surgery, but the
      superiority of laparoscopic access for appendectomy is widely debated. The
      authors analyze their monocentric experience with 1,347 laparoscopic
      appendectomies. METHODS: Between October 1991 and December 2002, all the patients
      with an indication for appendectomy underwent surgery (301 emergency and 1,046
      interval appendectomies) using the laparoscopic approach. RESULTS: For 1,248
      patients, appendectomy was performed laparoscopically, whereas for 99 patients
      (7.3%), it was converted to an open procedure because of technical reasons (90
      patients, 6.7%) or intraoperative complications (9 patients, 0.6%). For 59
      patients (4.4%), the appendectomy was associated with another procedure.
      Histology showed "acute" alterations in 261 of the 301 emergency surgeries and in
      148 of the 1,046 elective operations. Postoperative complications arose in 37
      patients (2.7%), with 5 patients (0.3%) requiring invasive treatment. The mean
      postoperative stay was 30 h. CONCLUSIONS: Laparoscopic appendectomy offers
      unquestionable advantages, but it is not yet considered the "gold standard" for
      appendiceal pathology. Many centers reserve it for selected patients (e.g., obese
      patients and women suspected of having other pathologies). No randomized trials
      or metaanalyses have definitively proved its superiority.

PMID- 16897294
TI  - Influence of nematodes on resource utilization by bacteria--an in vitro study.
AB  - The positive influence of bacterial feeding nematodes on bacterial mediated
      processes such as organic matter mineralization and nutrient cycling is widely
      accepted, but the mechanisms of these interactions are not always apparent. Both
      transport of bacteria by nematodes, and nutritional effects caused by nematode N
      excretion are thought to be involved, but their relative importance is not known
      because of the difficulties in studying these interactions in soil. We developed
      a simple in vitro assay to study complex nematode/bacterial interactions and used
      it to conduct a series of experiments to determine the potential influence of
      nematode movement and nutritional effects on bacterial resource use. The system
      used bacterial feeding and nonfeeding insect parasitic nematodes, and luminescent
      bacteria marked with metabolic reporter genes. Both nutritional enhancement of
      bacterial activity and bacterial transport were observed and we hypothesize that
      in nature, the relative importance of transport is likely to be greater in bulk
      soil, whereas nematode excretion may have greater impact in the rhizosphere. In
      both cases, the ability of nematodes to enhance bacterial resource utilization
      has implications for soil components of biogeochemical cycling.

PMID- 16897295
TI  - Assessing the contamination potential of freshly extracted Escherichia coli
      biofilm cells by impedancemetry.
AB  - Planktonic bacteria passing to a sessile state during the formation of a biofilm
      undergo many gene expression and phenotypic changes. These transformations
      require a significant time to establish. Inversely, cells extracted from a
      biofilm should also require a significant time before acquiring the same
      physiological characteristics as planktonic cells. Relatively few studies have
      addressed the kinetics of this inverse transformation process. We tested one
      aspect, namely, the contamination potential of freshly extracted Escherichia coli
      biofilm cells, precultured in a synthetic medium, in a rich liquid growth medium.
      We compared the time between inoculation and the beginning of the growth phase of
      freshly extracted biofilm cells, and suspended exponential and suspended
      stationary phase cells precultured in the same synthetic medium. Unexpectedly,
      the lag time for the extracted biofilm cells was the same as the lag time of the
      suspended exponential phase cells and significantly less than the lag time of the
      suspended stationary phase cells. The lag times were determined by an impedance
      technique. Cells extracted from biofilms, i.e., biofilms formed in canalizations
      and broken up by hydrodynamic forces, are an important source of contamination.
      Our work shows, in the case of E. coli, the high potential of freshly extracted
      biofilm cells to reinfect a new medium.

PMID- 16897296
TI  - Endophytic occupation of root nodules and roots of Melilotus dentatus by
      Agrobacterium tumefaciens.
AB  - Agrobacterium strains have been frequently isolated from the root nodules of
      different legumes. Various possible mechanisms have been proposed to explain the
      existence of these bacteria in nodules, but there is no sufficient experimental
      evidence to support the estimations. In this work, we proved that the
      Agrobacterium strain CCBAU 81181, which was originally isolated from the root
      nodules of Onobrychis viciaefolia, and a symbiotic strain of Sinorhizobium
      meliloti CCBAU 10062 could coinhabit the root nodules of Melilotus dentatus.
      Analyses were performed by using a fluorescence marker, reisolation of bacteria
      from nodules, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS
      PAGE) of whole cellular proteins, and polymerase chain reaction amplification of
      symbiotic genes. The inoculation of A. tumefaciens CCBAU 81181 did not affect the
      growth and nodulation of plants. CCBAU 81181 and 24 other Agrobacterium strains
      isolated from nodules were incapable of nodulating on their original or
      alternative host and 22 strains of these strains were endophytes in the roots and
      stems of their hosts. Also, the tumor-inducing A. tumefaciens strains IAM
      13129(T) and C58 were found capable of entering the roots of Glycyrrhiza
      pallidiflora, but did not cause pathogenic symptoms. With these results, we
      conclude that A. tumefaciens strains could be endophytic bacteria in the roots,
      stems, and root nodules. This finding partially explains why Agrobacterium
      strains were frequently isolated from the surface-sterilized nodules.

PMID- 16897297
TI  - The influence of tropical plant diversity and composition on soil microbial
      communities.
AB  - There is growing interest in understanding the linkages between above- and
      belowground communities, and very little is known about these linkages in
      tropical systems. Using an experimental site at La Selva Biological Station,
      Costa Rica, we examined whether plant diversity, plant community composition, and
      season influenced microbial communities. We also determined whether soil
      characteristics were related to differences in microbial communities.
      Phospholipid fatty acid (PLFA) composition revealed that microbial community
      composition differed across a plant diversity gradient (plots contained 1, 3, 5,
      or over 25 species). Plant species identity also was a factor influencing
      microbial community composition; PLFA composition significantly varied among
      monocultures, and among three-species combinations that differed in plant species
      composition. Differences among treatments within each of these comparisons were
      apparent in all four sampling dates of the study. There was no consistent shift
      in microbial community composition between wet and dry seasons, although we did
      see significant changes over time. Of all measured soil characteristics, soil C/N
      was most often associated with changes in microbial community composition across
      treatment groups. Our findings provide evidence for human alteration of soil
      microbial communities via the alteration of plant community composition and
      diversity and that such changes are mediated in part by changes in soil carbon
      quality.

PMID- 16897298
TI  - Environmental factors that influence the transition from lysogenic to lytic
      existence in the phiHSIC/Listonella pelagia marine phage-host system.
AB  - The marine phage varphiHSIC has been previously reported to enter into a
      pseudolysogenic-like interaction with its host Listonella pelagia. This phage
      host system displays behaviors that are characteristic of both pseudolysogeny and
      lysogeny including a high rate of spontaneous induction and chromosomal
      integration of the prophage. To determine what parameters may influence the
      transition from lysogenic to lytic existence in the varphiHSIC/L. pelagia phage
      host system, cultures of this organism were incubated under different
      environmental conditions, while host cell growth and bacteriophage production
      were monitored. The environmental parameters tested included salinity,
      temperature, a rapid temperature shift, and degree of culture aeration. The
      highest titers of phage were produced by HSIC-1a cells grown in high-salinity
      nutrient artificial seawater media (67 ppt with a natural salinity equivalent of
      57 ppt) or those cultured in highly aerated nutrient artificial seawater media
      (cultures shaken at 300 rpm). Conversely, the lowest titers of phage were
      produced under low salinity or rate of aeration. In general, conditions that
      stimulated growth resulted in greater lytic phage production, whereas slow growth
      favored lysogeny. These results indicate that elevated salinity and aeration
      influenced the switch from lysogenic to lytic existence for the phage varphiHSIC.
      These results may have implications for environmental controls of the lysogenic
      switch in natural populations of marine bacteria.

PMID- 16897300
TI  - Penicillium mycobiota in arctic subglacial ice.
AB  - Fungi have been only rarely isolated from glacial ice in extremely cold polar
      regions and were in these cases considered as random, long-term preserved Aeolian
      deposits. Fungal presence has so far not been investigated in polar subglacial
      ice, a recently discovered extreme habitat reported to be inhabited exclusively
      by heterotrophic bacteria. In this study we report on the very high occurrence
      (up to 9000 CFU L(-1)) and diversity of filamentous Penicillium spp. in the
      sediment-rich subglacial ice of three different polythermal Arctic glaciers
      (Svalbard, Norway). The dominant species was P. crustosum, representing on the
      average half of all isolated strains from all three glaciers. The other most
      frequently isolated species were P. bialowiezense, P. chrysogenum, P. thomii, P.
      solitum, P. palitans, P. echinulatum, P. polonicum, P. commune, P. discolor, P.
      expansum, and new Penicillium species (sp. 1). Twelve more Penicillium species
      were occasionally isolated. The fungi isolated produced consistent profiles of
      secondary metabolites, not different from the same Penicillium species from other
      habitats. This is the first report on the presence of large populations of
      Penicillium spp. in subglacial sediment-rich ice.

PMID- 16897299
TI  - Microbial availability and size fractionation of dissolved organic carbon after
      drought in an intermittent stream: biogeochemical link across the stream-riparian
      interface.
AB  - The evolution of dissolved organic carbon (DOC) molecular-weight fractions, DOC
      biodegradability (BDOC), DOC origin [fluorescence index (FI)], and enzyme
      activities between the stream waters (main and ephemeral channel) and ground
      waters (riparian and hillslope) were analyzed during the transition from drought
      to precipitation in a forested Mediterranean stream. After the first rains, DOC
      content in stream water reached its maximum value (10-18 mg L(-1)), being
      explained by the leaching of deciduous leaves accumulated on the stream bed
      during drought. During this period, the largest molecules (>10 kDa), were the
      most biodegradable, as indicated by high BDOC values measured during storm events
      and high enzymatic activities (especially for leucine-aminopeptidase). DOC >100
      kDa was strongly immobilized (78%) at the stream-riparian interface, whereas the
      smallest molecules (<1 kDa) were highly mobile and accumulated in ground waters,
      indicating their greater recalcitrance. Differential enzymatic patterns between
      compartments showed a fast utilization of polysaccharides in the flowing water
      but a major protein utilization in the ground water. The results of the FI
      indicated a more terrestrial origin of the larger molecules in the flowing water,
      also suggesting that transformation of material occurs through the stream
      riparian interface. Microbial immobilization and fast utilization of the most
      biodegradable fraction at the stream-riparian interface is suggested as a
      relevant DOC retention mechanism just after initial recharging of the ground
      water compartment. Large and rapid DOC inputs entering the intermittent river
      system during the transition from drought to precipitation provide available N
      and C sources for the heterotrophs. Heterotrophs efficiently utilize these
      resources that were in limited supply during the period of drought. Such changes
      in C cycling may highlight possible changes in organic matter dynamics under the
      prediction of extended drying periods in aquatic ecosystems.

PMID- 16897301
TI  - Response of rhizobial populations to moderate copper stress applied to an
      agricultural soil.
AB  - The use of pesticides in agricultural soils may affect the soil microbiota. The
      effect of repeated application of copper sulfate in soil on indigenous
      populations of rhizobia was assessed in a medium-term field experiment. Copper
      sulfate was applied over 8 years at two different rates, 12.5 and 50 kg of CuSO4
      ha(-1) year(-1), in the field. The concentrations of total copper in soil varied
      between 14.0 (control plots that did not receive copper sulfate) and 91.0 mg kg(
      1) (the most contaminated plots) at the time of sampling, 3 years after the end
      of the copper treatments. All the other physicochemical parameters were similar
      among the plots that also shared the same cropping history. The target rhizobia
      were monospecific populations of Rhizobium leguminosarum bv. viciae nodulating
      Vicia sativa and communities of rhizobial species nodulating Phaseolus vulgaris.
      The size of the vetch rhizobial populations was significantly reduced in the
      soils with the higher Cu content, whereas the size of the Phaseolus rhizobial
      populations was not significantly affected. However, the number of nodules formed
      on both vetches and common beans were reduced for the plants grown in the most
      contaminated soils, suggesting an additional toxic effect of copper on plant
      physiology. The diversity (Simpson's indices) of rhizobial genotypes, as
      characterized by polymerase chain reaction restriction fragment length
      polymorphism of 16S-23S rDNA intergenic spacer (IGS), was not influenced by
      copper application. Also, the genetic structure of the R. leguminosarum bv.
      viciae populations was not modified by copper treatments. By contrast, a shift
      was observed in the composition of the Phaseolus-nodulating communities in
      relation to soil copper content. The communities were composed of three 16S rDNA
      haplotypes: one corresponding to the R. leguminosarum (biovar phaseoli) species,
      the two others forming a new lineage of Phaseolus rhizobia based on 16S rDNA
      sequence analysis. The reduced frequency of the R. leguminosarum species in the
      Phaseolus-nodulating communities from the copper-treated soils was linked to its
      higher sensitivity to copper as compared to the higher tolerance of isolates
      belonging to the other rhizobial lineage. The new lineage was functionally
      efficient for symbiotic nitrogen fixation with P. vulgaris. Our results suggest
      that functional redundancy among species exhibiting variability for copper
      tolerance preserved the size of Phaseolus-nodulating communities. In contrast,
      the abundance of the vetch-nodulating rhizobia, which was a monospecific
      functional group mainly constituted by copper-sensitive genotypes, was adversely
      affected by repeated application of copper sulfate.

PMID- 16897302
TI  - Salmonella spp., Vibrio spp., Clostridium perfringens, and Plesiomonas
      shigelloides in marine and freshwater invertebrates from coastal California
      ecosystems.
AB  - The coastal ecosystems of California are highly utilized by humans and animals,
      but the ecology of fecal bacteria at the land-sea interface is not well
      understood. This study evaluated the distribution of potentially pathogenic
      bacteria in invertebrates from linked marine, estuarine, and freshwater
      ecosystems in central California. A variety of filter-feeding clams, mussels,
      worms, and crab tissues were selectively cultured for Salmonella spp.,
      Campylobacter spp., Escherichia coli-O157, Clostridium perfringens, Plesiomonas
      shigelloides, and Vibrio spp. A longitudinal study assessed environmental risk
      factors for detecting these bacterial species in sentinel mussel batches.
      Putative risk factors included mussel collection near higher risk areas for
      livestock or human sewage exposure, adjacent human population density, season,
      recent precipitation, water temperature, water type, bivalve type, and freshwater
      outflow exposure. Bacteria detected in invertebrates included Salmonella spp., C.
      perfringens, P. shigelloides, Vibrio cholerae, Vibrio parahaemolyticus, and
      Vibrio alginolyticus. Overall, 80% of mussel batches were culture positive for at
      least one of the bacterial species, although the pathogens Campylobacter, E. coli
      O157, and Salmonella were not detected. Many of the same bacterial species were
      also cultured from upstream estuarine and riverine invertebrates. Exposure to
      human sewage sources, recent precipitation, and water temperature were
      significant risk factors for bacterial detection in sentinel mussel batches.
      These findings are consistent with the hypothesis that filter-feeding
      invertebrates along the coast concentrate fecal bacteria flowing from land to sea
      and show that the relationships between anthropogenic effects on coastal
      ecosystems and the environmental niches of fecal bacteria are complex and
      dynamic.

PMID- 16897303
TI  - Microarray applications in microbial ecology research.
AB  - Microarray technology has the unparalleled potential to simultaneously determine
      the dynamics and/or activities of most, if not all, of the microbial populations
      in complex environments such as soils and sediments. Researchers have developed
      several types of arrays that characterize the microbial populations in these
      samples based on their phylogenetic relatedness or functional genomic content.
      Several recent studies have used these microarrays to investigate ecological
      issues; however, most have only analyzed a limited number of samples with
      relatively few experiments utilizing the full high-throughput potential of
      microarray analysis. This is due in part to the unique analytical challenges that
      these samples present with regard to sensitivity, specificity, quantitation, and
      data analysis. This review discusses specific applications of microarrays to
      microbial ecology research along with some of the latest studies addressing the
      difficulties encountered during analysis of complex microbial communities within
      environmental samples. With continued development, microarray technology may
      ultimately achieve its potential for comprehensive, high-throughput
      characterization of microbial populations in near real time.

PMID- 16897304
TI  - Identification of acetate- or methanol-assimilating bacteria under nitrate
      reducing conditions by stable-isotope probing.
AB  - Stable-isotope probing (SIP) was used to identify acetate- or methanol
      assimilating bacteria under nitrate-reducing conditions in activated sludge. A
      sludge sample obtained from wastewater treatment systems was incubated in a
      denitrifying batch reactor fed with synthetic wastewater containing
      [(13)C]acetate or [(13)C]methanol as the main carbon source and nitrate as the
      electron acceptor. We analyzed how growth of bacterial populations was stimulated
      by acetate or methanol as the external carbon source in nitrogen-removal systems.
      Most of the acetate- or methanol-assimilating bacteria identified by SIP have
      been known as denitrifiers in wastewater treatment systems. When acetate was used
      as the carbon source, 16S rRNA gene sequences retrieved from (13)C-labeled DNA
      were closely related to the 16S rRNA genes of Comamonadaceae (e.g., Comamonas and
      Acidovorax) and Rhodocyclaceae (e.g., Thauera and Dechloromonas) of the
      Betaproteobacteria, and Rhodobacteraceae (e.g., Paracoccus and Rhodobacter) of
      the Alphaproteobacteria. When methanol was used as the carbon source, 16S rRNA
      gene sequences retrieved from (13)C-DNA were affiliated with Methylophilaceae
      (e.g., Methylophilus, Methylobacillus, and Aminomonas) and Hyphomicrobiaceae.
      Rarefaction curves for clones retrieved from (13)C-DNA showed that the diversity
      levels for methanol-assimilating bacteria were considerably lower than those for
      acetate-assimilating bacteria. Furthermore, we characterized nitrite reductase
      genes (nirS and nirK) as functional marker genes for denitrifier communities in
      acetate- or methanol-assimilating populations and detected the nirS or nirK
      sequence related to that of some known pure cultures, such as Alcaligenes,
      Hyphomicrobium, and Thauera. However, most of the nirS or nirK sequences
      retrieved from (13)C-DNA were clustered in some unidentified groups. On the basis
      of 16S rRNA gene clone libraries retrieved from (13)C-DNA, these unidentified nir
      sequences might be identified by examining the nir gene in candidates for true
      denitrifiers (e.g., the families Comamonadaceae, Hyphomicrobiaceae,
      Methylophilaceae, and Rhodobacteraceae).

PMID- 16897306
TI  - Microbial exopolymers link predator and prey in a model yeast biofilm system.
AB  - Protistan grazing on biofilms is potentially an important conduit enabling energy
      flow between microbial trophic levels. Contrary to the widely held assumption
      that protistan feeding primarily involves ingestion of biofilm cells, with
      negative consequences for the biofilm, this study demonstrated preferential
      grazing on the noncellular biofilm matrix by a ciliate, with selective ingestion
      of yeast and bacterial cells of planktonic origin over attached and biofilm
      derived planktonic cells. Introducing a ciliate to two biofilm-forming
      Cryptococcus species, as well as two bacterial species in a model biofilm system,
      fluorescent probes were applied to determine ingestion of cellular and
      noncellular biofilm fractions. Fluoromicroscopy, as well as photometric
      quantification, confirmed that protistan grazing enhanced yeast biofilm
      metabolism, and an increase in biofilm biomass and viability. We propose that the
      extracellular polymeric matrix of biofilms may act as an interface regulating
      interaction between predator and prey, while serving as source of nutrients and
      energy for protists.

PMID- 16897305
TI  - Quorum sensing and phenazines are involved in biofilm formation by Pseudomonas
      chlororaphis (aureofaciens) strain 30-84.
AB  - The biological control bacterium Pseudomonas chlororaphis (aureofaciens) strain
      30-84 employs two quorum sensing (QS) systems: PhzR/PhzI regulates the production
      of the antibiotics phenazine-1-carboxylic acid, 2-hydroxy-phenazine-1-carboxylic
      acid, and 2-hydroxy-phenazine, whereas CsaR/CsaI regulates currently unknown
      aspects of the cell surface. Previously characterized derivatives of strain 30-84
      with mutations in each QS system and in the phenazine biosynthetic genes were
      screened for their ability to form surface-attached biofilm populations in vitro,
      using microtiter plate and flow cell biofilm assays, and on seeds and roots.
      Results from in vitro, seed, and root studies demonstrated that the PhzR/PhzI and
      the CsaR/CsaI QS regulatory systems contribute to the establishment of biofilms,
      with mutations in PhzR/PhzI having a significantly greater effect than mutations
      in CsaR/CsaI. Interestingly, phenazine antibiotic production was necessary for
      biofilm formation to the same extent as the PhzR/PhzI QS system, suggesting the
      loss of phenazines was responsible for the majority of the biofilm defect in
      these mutants. In vitro analysis indicated that genetic complementation or AHL
      addition to the growth medium restored the ability of the AHL synthase phzI
      mutant to form biofilms. However, only phenazine addition or genetic
      complementation of the phenazine biosynthetic mutation in trans restored biofilm
      formation by mutants defective in the transcriptional activator phzR or the phzB
      structural mutant. QS and phenazine production were also involved in the
      establishment of surface-attached populations on wheat seeds and plant roots,
      and, as observed in vitro, the addition of AHL extracts restored the ability of
      phzI mutants, but not phzR mutants, to form surface attached populations on
      seeds. Similarly, the presence of the wild type in mixtures with the mutants
      restored the ability of the mutants to colonize wheat roots, demonstrating that
      AHL and/or phenazine production by the wild-type population could complement the
      AHL- and phenazine-deficient mutants in situ. Together, these data demonstrate
      that both QS systems are involved in the formation of surface-attached
      populations required for biofilm formation by P. chlororaphis strain 30-84, and
      indicate a new role for phenazine antibiotics in rhizosphere community
      development beyond inhibition of other plant-associated microorganisms.

PMID- 16897307
TI  - Effect of marine bacterial isolates on the growth and morphology of axenic
      plantlets of the green alga Ulva linza.
AB  - The green marine macroalga, Ulva linza, adopts an "atypical" form when grown in
      the absence of bacteria. Twenty unique strains of periphytic bacteria, isolated
      from three species of Ulva, were identified by 16S rDNA sequencing. These
      isolates were assessed for their effect on the growth and morphological
      development of axenic plantlets of U. linza. Results showed that the effect of
      bacterial strains was strain- but not taxon-specific. Thirteen isolates returned
      the aberrant morphology to normal and of these, five also significantly increased
      growth rate. One isolate increased growth, but had no effect on morphology.
      Biofilms of some of these isolates stimulated the settlement of Ulva zoospores
      but there was no correlation between bacterial isolates that stimulated zoospore
      settlement and those that initiated changes in morphology and/or growth of the
      cultured alga.

PMID- 16897308
TI  - Screening possible mechanisms mediating cadmium resistance in Rhizobium
      leguminosarum bv. viciae isolated from contaminated Portuguese soils.
AB  - Environment heavy-metal contamination is now widespread. Soils may become
      contaminated from a variety of anthropogenic sources, such as smelters, mining,
      industry, and application of metal-containing pesticides and fertilizers. Soil
      microorganisms are very sensitive to moderate heavy-metal concentrations.
      Therefore, the present work was designed to screen possible mechanisms involved
      in Rhizobium's Cd resistance; with this purpose, we determined the tolerance
      levels of several isolates originated from sites with different heavy-metal
      contamination. Whole-cell-soluble proteins and plasmid profiles were analyzed. We
      also determined Cd cell concentrations and lipopolysaccharide (LPS) amounts.
      Results showed different tolerances among Rhizobium isolates; according to their
      maximum resistance level, isolates were divided in four groups: sensitive (0-125
      microM CdCl(2)), moderately tolerant (125-210 microM CdCl(2)), tolerant (250-500
      microM CdCl(2)), and extremely tolerant (> or =750 microM CdCl(2)). Intracellular
      Cd concentrations were lower when compared to wall-bound Cd. Unexpectedly,
      extremely tolerant isolates accumulated higher levels of metal, suggesting the
      presence of intracellular agents that prevent metal interfering with important
      metabolic pathways. The electrophoretic patterns of whole-cell-soluble proteins
      evidenced cadmium as an inducer of protein metabolism alterations, which were
      more evident in some polypeptides. Plasmid profiles also showed differences; most
      tolerant isolates presented two plasmids with molecular weights of 485 and 415
      kb, indicating that extrachromosomal DNA may be involved in cadmium resistance.
      LPS showed to be a common mechanism of resistance. However, the degree of
      tolerance conferred by LPS is not enough to support tolerance to the higher
      levels of stress imposed. Presence of other resistance mechanisms is currently
      being investigated.

PMID- 16897309
TI  - Effect of agricultural management regime on Burkholderia community structure in
      soil.
AB  - The main objective of this study was to determine the Burkholderia community
      structure associated with areas under different agricultural management and to
      evaluate to which extent this community structure is affected by changes in
      agricultural management. Two fields with distinct soil history (arable land and
      permanent grassland) were exposed to three agricultural management regimes (crop
      rotation, maize monoculture, and grassland). By using a culture-independent
      approach, based on a Burkholderia-specific polymerase chain reaction-denaturing
      gradient gel electrophoresis system, it was possible to observe the conversion of
      Burkholderia communities typical for permanent grassland to those of arable land
      after four consecutive years. However, the time needed to achieve the reverse
      transition, i.e., converting the Burkholderia community associated with arable
      land to that of grassland, was beyond the duration of the field experiment. In
      addition, by applying principal response curves, the direction and extent of the
      conversion from grassland to arable land (maize monoculture and to crop rotation)
      were determined. Hence, the results suggested that agricultural practices, such
      as fertilization and tillage, were more effective in changing the Burkholderia
      community structure than agricultural management regime. To determine the effect
      of agricultural management on the Burkholderia population with biocontrol
      abilities, the culturable fraction of the Burkholderia community was assessed.
      The areas under permanent grassland and grassland converted to maize monoculture
      had the highest percentages of Burkholderia strains with antagonistic activity
      against Rhizoctonia solani AG-3, mainly Burkholderia pyrrocinia and Burkholderia
      sp. LMG 22929. The isolation frequency of antagonistic isolates from arable land
      was extremely low. Our results indicate that (changes in) agricultural
      management, mainly crop rotation, affect the frequency of isolation of
      antagonistic Burkholderia strains and that grassland represents a reservoir of
      Burkholderia species with great potential for agricultural applications.

PMID- 16897310
TI  - Structural and functional responses of a sewage microbial community to dilution
      induced reductions in diversity.
AB  - The relationship between functional redundancy and microbial community structure
      diversity was examined using laboratory incubations to ensure constant
      environmental conditions. Serial dilutions of a sewage microbial community were
      prepared, used to inoculate sterile sewage, and maintained in batch culture.
      Probability suggests that dilution of the initial community should remove rare
      organism types, creating mixtures of cells differing in diversity. Regrowth of
      the diluted mixtures generated communities similar in abundance but differing in
      community structure and relative diversity (as determined using two DNA
      fingerprinting techniques and dilution-to-extinction analysis of community-level
      physiological profiles). The in situ function of each regrown community was
      examined by monitoring the short-term uptake of five different (14)C-labeled
      compounds (glucose, acetate, citrate, palmitic acid, and an amino acid mixture).
      No significant differences were detected between treatments in either the rate of
      uptake of a substrate or the efficiency with which each community assimilated
      each compound. The fact that the activity of the original community was the same
      as that of a community regrown from an inoculum containing fewer that 100 cells
      (10(-6) dilution) indicates that functional redundancy was quite high in this
      system. For each organism type eliminated during the dilution process, at least
      one of the remaining types was able to provide the same function at the same
      level as the lost one. Further research is necessary to determine what impact
      this functional redundancy may have on overall ecosystem function and stability.

PMID- 16897311
TI  - Resource-limited heterotrophic prokaryote production and its potential
      environmental impact associated with Mn nodule exploitation in the northeast
      equatorial pacific.
AB  - Shipboard enrichment incubation experiments were performed to elucidate the
      limiting resources for heterotrophic prokaryotic production and to discuss the
      potential impact of bottom water and sediment discharges in relation to manganese
      (Mn) nodule exploitation on the heterotrophic prokaryotes in the oligotrophic
      northeast equatorial Pacific. Compared to an unamended control, the production of
      heterotrophic prokaryotes increased 25-fold in water samples supplemented with
      amino acids (i.e., organic carbon plus nitrogen), whereas the production
      increased five and two times, respectively, in samples supplemented with either
      glucose or ammonium alone. These results indicate that heterotrophic prokaryote
      production in the northeast equatorial Pacific was co-limited by the availability
      of dissolved organic carbon and inorganic nitrogen. In samples from the nutrient
      depleted surface mixed layer (10-m depth), the addition of a slurry of bottom
      water and sediment doubled heterotrophic prokaryote production compared to an
      unamended control, whereas sonicating the slurry prior to addition quadrupled the
      production rate. However, little difference was observed between an unamended
      control and slurry-amended samples in the subsurface chlorophyll a (Chl a)
      maximum (SCM) layer. Thus, the impact of slurry discharge is more significant at
      the nutrient-depleted surface mixed layer than at the high-nutrient SCM layer.
      The greatly enhanced prokaryote production resulting from the addition of
      sonicated slurry further suggests that dissociated organic carbon may directly
      stimulate heterotrophic prokaryote production in the surface mixed layer.
      Overall, the results suggest that the surface discharge of bottom water and
      sediments during manganese nodule exploitation could have a significant
      environmental impact on the production of heterotrophic prokaryotes that are
      currently resource limited.

PMID- 16897312
TI  - A novel approach incorporating sildenafil in the management of symptomatic
      neonates with Ebstein's anomaly.
AB  - The neonatal presentation of Ebstein's anomaly is a distinct cyanotic lesion for
      which little can be done other than to maintain ductal patency or perform
      palliative surgery if improvement does not occur. We report two cases in which
      sildenafil was introduced to assist previously failed attempts at weaning of
      prostaglandin.

PMID- 16897313
TI  - A criss-cross heart with twisted atrioventricular connections, "perfect
      streaming," and double discordance.
AB  - At 24 weeks gestational age, a term female infant was diagnosed with complex
      congenital heart disease. The antenatal cardiac diagnosis was uncertain and
      included univentricular heart. Following delivery, the child remained well and
      was normally saturated. Echocardiography and angiocardiography revealed an
      unusual relationship between atria and ventricles.

PMID- 16897314
TI  - Diagnosis of perigraft seroma by use of different techniques in infants with
      respiratory distress after modified Blalock-Taussig shunt.

PMID- 16897316
TI  - Efficacy of signal-averaged electrocardiography in the young orthotopic heart
      transplant patient to detect allograft rejection.
AB  - Endomyocardial biopsy is the gold standard survey for cardiac graft rejection.
      Signal-averaged electrocardiography (SAECG) identifies slowly conducting,
      diseased myocardium. We sought to determine whether SAECG is a sensitive,
      noninvasive transplant surveillance method in the young.Ninety-four SAECGs
      recorded prior to biopsy in 20 young transplant (OHT) patients and those from 15
      healthy age-matched controls (CTL) were analyzed. In the OHT group, 56 no
      rejection (NOREJ) (ISHLT grades 0 or 1 A) and 37 acute rejection (REJ) (ISHLT
      grades IB, 2, and 3A) SAECGs were compared, SAECGs were filtered at 40-255 Hz.
      Total QRS duration (QRSd), duration of terminal low amplitude of QRS under 40
      microV (LAS), and root mean square amplitude of terminal 40 msec of QRS (RMS40)
      were compared.SAECGs were significantly different in CTL vs NOREJ but not in
      NOREJ vs REJ: QRSd, 81.7 +/- 8, 107.2 +/- 18.4, and 112.3 +/- 21.6 msec,
      respectively; LAS, (18 +/- 5.8, 23.6 +/- 10.7, and 27 +/- 14.8 msec,
      respectively; and RMS40, (169.3 +/- 100.4, 68 +/- 48.8, and 57.5 +/- 45.6 microV,
      respectively. Children following OHT exhibited significant differences in the
      SAECG compared to controls. Differences between the NOREJ and REJ groups were
      negligible. Therefore, SAECG may not be effective in detecting OHT rejection in
      the young.

PMID- 16897317
TI  - Metabolic alterations and neurodevelopmental outcome of infants with
      transposition of the great arteries.
AB  - Abnormal neurodevelopment has been reported for infants who were born with
      transposition of the great arteries (TGA) and underwent arterial switch operation
      (ASO). This study evaluates the cerebral metabolism of TGA infants at birth and
      before ASO and neurodevelopment 1 year after ASO. Proton magnetic resonance
      spectroscopy (1H-MRS) was performed on 16 full-term TGA brains before ASO within
      3-6 days after birth. The brain metabolite ratios of [NAA/Cr], [Cho/Cr], and
      [mI/Cr] evaluated measured. Ten infants were evaluated at 1 year using the Bayley
      Scales of Infants Development II (BSED II). Cerebral metabolism of infants with
      TGA was altered in parietal white matter (PWM) and occipital gray matter (OGM) at
      birth before ASO. One year after ASO, [Cho/Cr] in PWM remained altered, but all
      metabolic ratios in OGM were normal. The results of BSID II at 1 year showed
      delayed mental and psychomotor development. This delayed neurodevelopmental
      outcome may reflect consequences of the altered cerebral metabolism in PWM
      measured by 1H-MRS. It is speculated that the abnormal hemodynamics due to TGA in
      utero may be responsible for the impaired cerebral metabolism and the subsequent
      neurodevelopmental deficit.

PMID- 16897318
TI  - Longitudinally quantitative 2-deoxy-2-[18F]fluoro-D-glucose micro positron
      emission tomography imaging for efficacy of new anticancer drugs: a case study
      with bortezomib in prostate cancer murine model.
AB  - PURPOSE: The aim of this study was to validate quantitative metabolic response of
      tumors to a treatment measured by longitudinal 2-deoxy-2-[(18)F]fluoro-D-glucose
      (FDG) micro positron emission tomography (microPET) as a robust tool for
      preclinical evaluation of new anticancer agents. PROCEDURES: Severe combined
      immunodeficiency mice with CWR22 xenografts were intravenously treated with
      bortezomib (Velcade) at 0.8 mg/kg on days 0, 3, 7, 10, and 14 and imaged with FDG
      microPET before, during and after treatment. Quantitative indices of tumor FDG
      uptake were developed. RESULTS: FDG microPET images successfully revealed the
      gradual reduction of tumor FDG uptake on day 4 onward despite no absolute tumor
      shrinkage. The standardized uptake values of FDG in tumors was reduced to 43% of
      the baseline values. Using the total tumor FDG uptake as the viable tumor burden,
      we found 86% tumor inhibition, compared to a 55% tumor growth inhibition in tumor
      volume measurement. CONCLUSION: FDG microPET imaging can provide an additional
      dimension of the efficacy of anticancer therapies that may otherwise be
      underestimated by tumor volume measurement.

PMID- 16897319
TI  - Evaluation of the integrity of the dopamine system in a rodent model of
      Parkinson's disease: small animal positron emission tomography compared to
      behavioral assessment and autoradiography.
AB  - PURPOSE: In the 6-hydroxydopamine (6-OHDA) rat model of Parkinson's disease (PD),
      it is important to determine lesion severity. This evaluation can be performed in
      vivo, through evaluation of dopamine (DA)-dependent motor function or with small
      animal positron emission tomography (microPET), or at postmortem, by examining
      markers for DA neurons. PROCEDURES: Rats were given mild or severe unilateral 6
      OHDA lesions, scanned with the tracer [(11)C](+/-)dihydrotetrabenazine
      ([(11)C]DTBZ), and tested on a tapered/ledged beam-walking task. At postmortem,
      autoradiography was performed with [(11)C]DTBZ. RESULTS: Autoradiography was
      significantly correlated with microPET and behavioral scores, whereas the
      microPET and behavioral data were not significantly correlated. CONCLUSIONS: This
      study shows that behavioral analysis, microPET, and autoradiography are all good
      tools for measuring the integrity of the DA system, and demonstrates the utility
      of the tapered/ledged beam-walking test to screen for lesion severity, as well as
      the importance of including postmortem analysis after in vivo imaging studies.

PMID- 16897320
TI  - Molecular imaging of EGFR kinase activity in tumors with 124I-labeled small
      molecular tracer and positron emission tomography.
AB  - Positron emission tomography (PET) with epidermal growth factor receptor (EGFR)
      kinase-specific radiolabeled tracers could provide the means for noninvasive and
      repetitive imaging of heterogeneity of EGFR expression and signaling activity in
      tumors in individual patients before and during therapy with EGFR signaling
      inhibitors. We developed the synthesis and (124)I-radiolabeling of the (E)-But-2
      enedioic acid [4-(3-[(124)I]iodoanilino)-quinazolin-6-yl]-amide-(3-morpholin-4-yl
      propyl)-amide (morpholino-[(124)I]-IPQA), which selectively, irreversibly, and
      covalently binds the adenosine-triphosphate-binding site to the activated
      (phosphorylated) EGFR kinase, but not to the inactive EGFR kinase. The latter was
      demonstrated using in silico modeling with crystal structures of the wild type
      and different gain-of-function mutants of EGFR kinases. Also, this was
      demonstrated by selective radiolabeling of the EGFR kinase domain with morpholino
      [(131)I]-IPQA in A431 human epidermoid carcinoma cells and Western blot
      autoradiography. In vitro radiotracer accumulation and washout studies
      demonstrated a rapid accumulation and progressive retention postwashout of
      morpholino-[(131)I]-IPQA in A431 epidermoid carcinoma and in U87 human glioma
      cells genetically modified to express the EGFRvIII mutant receptor, but not in
      the wild-type U87MG glioma cells under serum-starved conditions. Using morpholino
      [(124)I]-IPQA, we obtained noninvasive PET images of EGFR activity in A431
      subcutaneous tumor xenografts, but not in subcutaneous tumor xenografts grown
      from K562 human chronic myeloid leukemia cells in immunocompromised rats and
      mice. Based on these observations, we suggest that PET imaging with morpholino
      [(124)I]-IPQA should allow for identification of tumors with high EGFR kinase
      signaling activity, including brain tumors expressing EGFRvIII mutants and
      nonsmall-cell lung cancer expressing gain-of-function EGFR kinase mutants.
      Because of significant hepatobiliary clearance and intestinal reuptake of the
      morpholino-[(124)I]-IPQA, additional [(124)I]-IPQA derivatives with improved
      water solubility may be required to optimize the pharmacokinetics of this class
      of molecular imaging agents.

PMID- 16897321
TI  - A CT database for research, development and education: concept and potential.
AB  - Both in radiology and in surgery, numerous applications are emerging that enable
      3D visualization of data from various imaging modalities. In clinical practice,
      the patient's images are analyzed on work stations in the Radiology Department.
      For specific preclinical and educational applications, however, data from single
      patients are insufficient. Instead, similar scans from a number of individuals
      within a collective must be compiled. The definition of standardized acquisition
      procedures and archiving formats are prerequisite for subsequent analysis of
      multiple data sets. Focusing on bone morphology, we describe our concept of a
      computer database of 3D human bone models obtained from computed tomography (CT)
      scans. We further discuss and illustrate deployment areas ranging from prosthesis
      design, over virtual operation simulation up to 3D anatomy atlases. The database
      of 3D bone models described in this work, created and maintained by the AO
      Development Institute, may be accessible to research institutes on request.

PMID- 16897322
TI  - Generation of the central masticatory pattern and its modification by sensory
      feedback.
AB  - Mammalian mastication results from the interaction of an intrinsic rhythmical
      neural pattern and sensory feedback generated by the interaction of the effecter
      system (muscles, bones, joints, teeth, soft tissues) with food. The main
      variables that explain variation in the pattern of human mastication are the
      subjects themselves, their age, the type of food being eaten, and time during a
      sequence of movements. The intrinsic pattern of mastication is generated by a
      central pattern generator (CPG) located in the pons and medulla. The output of
      the CPG is modified by inputs that descend from higher centers of the brain and
      by feedback from sensory receptors. Intraoral touch receptors, muscle spindles in
      the jaw-closing muscles, and specialized mechanoreceptors in the periodontal
      ligament have especially powerful effects on movement parameters.

PMID- 16897323
TI  - Hyoid-bolus transit latencies in normal swallow.
AB  - Pharyngeal swallow delay is frequently found in dysphagic patients and is thought
      to be a factor in a range of swallowing problems, including aspiration. Implicit
      in notions of swallow "delay" is a temporal interval between two events that is
      longer than normal. However, there appears to be little agreement about which
      referent events should be considered in determining delay. A number of pharyngeal
      bolus transit points and various pharyngeal gestures have been used in delays
      determined from fluoroscopic evidence, and other referents have been used in
      electromyographic and manometric studies of swallow. In this study latencies
      between the first movement of the hyoid and several pharyngeal bolus transit
      points were calculated from fluoroscopic swallow studies in normal nondysphagic
      adults. Means and standard deviations of these latencies are provided for a 3-cc
      and a 20-cc bolus and for both nonelderly and elderly adults. The data may be a
      useful resource for relating the specific latencies investigated to concepts of
      pharyngeal swallow delay, in particular, when assessing videofluoroscopic studies
      using a similar protocol.

PMID- 16897324
TI  - Sound component duration of healthy human pharyngoesophageal swallowing: a gender
      comparison study.
AB  - Cervical auscultation is a noninvasive technique for studying swallowing that was
      first used in the 1960s. The aim of our study was to use the numeric acoustic
      recording technique for analyzing swallowing sound signals in healthy subjects
      while they ingested a defined volume and consistency of a specific substance.
      Twenty males and ten females were included in the study and given 10 ml of a
      barium suspension to swallow. A microphone was placed on the skin overlying the
      lateral border of the trachea, directly under the inferior border of the cricoid,
      and connected to a computer. For each sound recording, the total duration of the
      sound (td), the number (n) of sound components (SC), the duration of each SC (c1,
      c2, c3,...), and the intervals (i1, i2,...) between the SCs were measured. For
      all the recordings, the mean durations of acoustic parameters (TDm, C1m, C2m,
      C3m, I1m, I2m) were calculated and compared by using Student's t test. In the 20
      male subjects, the mean acoustic parameters were calculated (MTDm, MC1m, MC2m,
      MC3m, MI1m, MI2m) and compared with the mean acoustic parameters (FTDm, FC1m,
      FC2m, FC3m, FI1m, FI2m) in the ten females by using a Wilcoxon nonparametric
      statistical test. We were able to interpret 80% of the recordings. The TDm was
      710 +/- 28 ms. Three main SCs were detected: C1m = 100 +/- 56, C2m = 150 +/- 90,
      C3m = 80 +/- 54 ms; I1m = 100 +/- 66, I2m = 190 +/- 120 ms. No significant
      difference in these parameters was observed with respect to gender. This study
      enabled us to decompose the swallowing sounds into three main SCs and to quantify
      their normal durations. These results should prove useful for the assessment of
      sound variations in pathologic conditions.

PMID- 16897325
TI  - A questionnaire study to assess long-term outcome in patients with abnormal
      esophageal manometry.
AB  - Patients with unexplained chest pain or dysphagia are often referred for
      esophageal manometric studies to further investigate their symptoms. Four main
      manometric abnormalities have been described: achalasia, diffuse esophageal
      spasm, "nutcracker" (hypercontracting) esophagus, and hypocontracting esophagus.
      With the exception of achalasia, treatments are of limited benefit and the
      natural history of these conditions is largely unknown. We sent questionnaires to
      patients who were investigated at least three years before our study began. They
      repeated a DeMeester symptom questionnaire that they had completed at the time of
      their initial study. Questionnaires were sent to 137 patients with diffuse
      esophageal spasm, "nutcracker" (hypercontracting) esophagus, or hypocontracting
      esophagus. We also sent questionnaires to 57 patients with dysphagia or chest
      pain who had had normal esophageal manometry and pH studies. These patients acted
      as symptomatic controls. Responses were compared using the Wilcoxon signed ranks
      test. Seventy-two (53%) patients with diffuse esophageal spasm, "nutcracker"
      esophagus, or hypocontracting esophagus replied. An additional 8 (6%) patients
      died. Symptom scores in all three conditions had improved significantly over time
      (p < or = 0.01 for each condition, Wilcoxon signed ranks test). Patients with
      dysphagia or chest pain but normal esophageal studies had not improved. The
      significance of diffuse esophageal spasm, "nutcracker" esophagus, and
      hypocontracting esophagus found at esophageal manometry remains uncertain.
      Although treatment is often ineffective, these conditions typically run a benign
      course. Patients can be reassured that their symptoms are likely to improve with
      time.

PMID- 16897326
TI  - Management of diverticulitis in younger patients.
AB  - PURPOSE: This study was designed to evaluate the clinical course of sigmoid
      diverticulitis patients younger than aged 50 years examined by abdominal CT
      during the first episode of disease to elucidate whether the criteria used for
      older patients can safely be followed in their younger counterparts. METHODS:
      Retrospective review of patients with sigmoid diverticulitis treated from 1990 to
      2003 was performed. INCLUSION CRITERIA: patients younger than aged 50 years with
      sigmoid diverticulitis documented by CT scan. Severity of disease was classified
      according to radiographic findings. Age, gender, treatment, recurrent disease,
      and need for colostomy were documented. RESULTS: A total of 5,499 patients were
      identified with sigmoid diverticulitis: 962 patients were younger than aged 50
      years, and 411 had a CT scan on their first episode of disease. Of the 411
      patients, 335 were classified as uncomplicated and 76 were complicated. Of the
      uncomplicated patients, 101 underwent an elective operation and 234 were followed
      nonoperatively. Of those followed, 67 had a recurrent uncomplicated episode, 10
      had a recurrent complicated episode, of whom 5 required emergent operation and
      colostomy. Of the 76 patients with complicated disease, 23 had an emergent
      operation with colostomy, and 38 had an elective operation. Fifteen patients were
      followed without an operation and seven had a recurrent uncomplicated episode.
      None required emergent operation or colostomy. CONCLUSIONS: Younger patients with
      uncomplicated diverticulitis by CT criteria respond well to medical management
      and seldom required an emergent operation and colostomy. Young patients with
      diverticulitis should be treated according to the same criteria used for older
      patients.

PMID- 16897327
TI  - Desmoid tumor arising at the colostomy site after abdominoperineal resection for
      rectal carcinoma: report of a case.
AB  - A 69-year-old male who developed a desmoid tumor at the site of his end colostomy
      after abdominoperineal resection for rectal carcinoma is reported. The tumor was
      resected with wide margins. Histopathology revealed desmoid tumor of the anterior
      abdominal wall with no malignant features. The patient had an uneventful
      postoperative course. To our knowledge, this is the first case of solitary
      desmoid tumor of anterior abdominal wall at the colostomy site reported in the
      literature.

PMID- 16897328
TI  - Loop ileostomy morbidity: timing of closure matters.
AB  - PURPOSE: Diverting stomas are commonly performed during ileoanal and coloanal
      anastomoses. We studied a series of patients after loop ileostomy closure to
      determine risk factors and the impact of the interval from primary operation on
      morbidity. METHODS: Ninety-three consecutive patients undergoing loop ileostomy
      closure at a single institution after coloanal or ileoanal anastomosis were
      retrospectively reviewed. Complications were classified as medical or surgical
      according to its treatment requirements. Results were correlated to clinical and
      operative features. RESULTS: Of the 93 patients, 43 were male and 50 were female
      with mean age of 56 years. Overall, complication rate was 17.2 percent. The most
      common complication was small-bowel obstruction. Complications required operative
      management in 3.2 percent and medical management alone in 14 percent. There was
      no mortality. There was no correlation between complication occurrence and age,
      gender, type of suture (manual or mechanical), and operative time. Complications
      were significantly associated with primary disease and shorter interval between
      primary operation and ileostomy closure. Regarding the optimal interval between
      primary surgery and ileostomy closure, the cutoff value for increased risk of
      developing postoperative complications was 8.5 weeks, below which the risk of
      such occurrence was significantly higher with a sensitivity rate of 88 percent.
      CONCLUSIONS: Diverting loop ileostomy adds little cumulative morbidity to the
      primary operation and is a safe option for diversion to protect a low colorectal
      anastomosis. To further reduce morbidity, the interval between primary operation
      and ileostomy closure should be no shorter than 8.5 weeks.

PMID- 16897329
TI  - Ipsilateral ileal conduit placement at vertical rectus abdominis myocutaneous
      flap donor site in pelvic exenteration.
AB  - Placing of ileal conduit at the time of pelvic exenteration in combination with a
      same-side vertical rectus abdominis myocutaneous flap is controversial. We report
      our experience with the placement of the ileal conduit at the same side as the
      donor site of the vertical rectus abdominis myocutaneous flap in 12 patients and
      describe our technical approach.

PMID- 16897330
TI  - Omentoplasty in abdominoperineal resection: a review of the literature using a
      systematic approach.
AB  - PURPOSE: Abdominoperineal resection is associated with considerable morbidity, in
      particular, the perineal wound. Omentoplasty has been proposed as a means of
      reducing the perineal complication rate after abdominoperineal resection. This
      study was designed to assess the available evidence for omentoplasty in
      abdominoperineal resection. METHODS: A MEDLINE search from January 1970 to July
      2005 was performed to locate English language articles relating to omentoplasty
      in abdominoperineal resection. Manual search via reference lists identified
      additional articles. Articles reporting results from at least ten patients in
      whom abdominoperineal resection with an omentoplasty was performed were
      considered. All included reports were reviewed by using a predetermined protocol.
      RESULTS: Among the ten reports identified, no randomized trials, four studies
      with control groups, and six case series were found. Primary healing was the
      outcome measure that was most consistently reported in the different articles.
      Most authors reported positive results after omentoplasty, and one study showed
      significant improvement in perineal healing rate at six months. Significant
      reduction in sinus formation and wound dehiscence also was reported. Only few
      complications related to the omentoplasty, none of which was fatal, were
      reported. CONCLUSIONS: Although results from the studies included in this review
      indicate that there may be benefits from including an omentoplasty when
      performing an abdominoperineal resection, the lack of randomized studies results
      in only weak evidence.

PMID- 16897331
TI  - Surgical treatment of Chagasic megacolon by abdominal rectosigmoidectomy with
      immediate posterior end-to-side stapling (Habr-Gama technique).
AB  - PURPOSE: Various techniques have been used in the surgical treatment of Chagasic
      megacolon, including sympathectomy, sphincterotomy, anterior abdominal resection
      with high or low anastomosis, pull-through procedures, and Duhamel technique.
      However, results have not been consistently satisfactory, with reportedly high
      morbidity and mortality rates. The purpose of this study was to assess the
      technique and results of anterior rectosigmoidectomy with immediate posterior
      colorectal end-to-side stapled anastomosis for the treatment of Chagasic
      megacolon. METHODS: A prospective, noncontrolled study between 1989 and 2000
      analyzed 49 patients with Chagasic megacolon. Preoperative barium enema confirmed
      Chagasic megacolon in all patients and preoperative anorectal manometry in 33
      patients (67 percent). Rectal stump closure was undertaken by surgical stapling
      in 41 patients (84 percent); mechanical colorectal anastomosis was accomplished
      with a circular stapler in all patients. RESULTS: Symptoms of intestinal
      constipation ranged from 6 months to 40 years, Chagas' serology was positive in
      98 percent of patients, 41 percent used bowel enemas for evacuation, and 71
      percent had a history of fecaloma. The overall postoperative complication rate
      was 20 percent. Surgical complications occurred in 18 percent, 2 percent had
      nonsurgical complications, and there was no mortality. Postoperative barium enema
      was performed in 82 percent of cases, confirming the absence of disease.
      Postoperative anorectal manometry demonstrated normal resting pressure and rectal
      capacity; the inhibitory reflex remained absent and rectal sensitivity was
      increased. Ninety-three percent of patients were followed for more than 48
      months, and all patients reported daily stool elimination without recurrence of
      constipation. CONCLUSIONS: The current study indicates that our technique is
      effective for surgical treatment of patients with Chagasic megacolon.

PMID- 16897332
TI  - Transperineal repair of persistent rectovaginal fistulas using an acellular
      cadaveric dermal graft (AlloDerm).
AB  - A number of surgical techniques have been described to treat rectovaginal
      fistulas. Recurrent or persistent fistulas after previous repair can be
      particularly difficult to treat. We report a novel technique used to successfully
      repair rectovaginal fistulas after failed mucosal advancement flap procedures
      using a transperineal-layered closure with an interposed graft of acellular
      cadaveric dermis (Alloderm).

PMID- 16897333
TI  - Endoscopic mucosal resection of large sessile colorectal polyps with submucosal
      injection of hypertonic 50 percent dextrose-epinephrine solution.
AB  - PURPOSE: Before endoscopic mucosal resection of large sessile colorectal polyps,
      injection of solution into submucosa cushions and isolates the tumor, although
      there is little information as to which solution with optimal effect should be
      used. This study investigated the effectiveness of endoscopic mucosal resection
      by use of a hypertonic dextrose plus epinephrine solution for large sessile
      colorectal polyps. METHODS: We removed 59 large sessile colorectal polyps in 59
      patients by introducing an endoscopic submucosal hypertonic dextrose plus
      epinephrine injection technique. Endoscopic evaluations were repeated at 3, 6,
      and 12 months or longer. If no residual tumor was observed endoscopically and
      histologically at one year or more, the patient was considered to be "cured." The
      main outcome measurements were the mean amount of solution injected, mean
      disappearance time of solution, safety, complications, and recurrence at follow
      up. RESULTS: Of the 59 large sessile colorectal polyps, 23 (39 percent) were
      resected en bloc and 36 (61 percent) piecemeal. The mean amount of hypertonic
      dextrose plus epinephrine solution injected was 24.42 +/- 17.52 ml, and its mean
      disappearance time was 13.61 +/- 5.21 (range, 7-21) minutes. Of the 36 patients
      treated with piecemeal resection, 18 (50 percent) required additional endoscopic
      interventions. In patients who entered the follow-up surveillance protocol for
      one year or longer, the cure rate by en bloc resection was 100 percent (23/23)
      and that by piecemeal intervention was 96.78 percent (30/31). Four patients (6.8
      percent) had local bleeding after endoscopic mucosal resection that was mainly
      controlled endoscopically. CONCLUSIONS: Endoscopic mucosal resection after
      submucosal hypertonic dextrose plus epinephrine solution injection, with an
      intensive follow-up program, seems to be a safe and effective treatment for large
      sessile colorectal polyps.

PMID- 16897335
TI  - The passing of the United Ostomy Association.

PMID- 16897334
TI  - Management of acute diverticulitis in the East Anglian region: results of a
      United Kingdom regional survey.
AB  - PURPOSE: Acute diverticulitis is the most common presentation of diverticular
      disease; however, no published guidelines for management are available in the
      United Kingdom. This survey was designed to assess the current United Kingdom
      regional practice compared with the guidelines published by The American Society
      of Colon and Rectal Surgeons. METHODS: A questionnaire survey focused on the
      management of acute diverticulitis was sent to all consultants, specialist
      registrars, and staff-grade surgeons in general surgery in one United Kingdom
      region. RESULTS: Eighty-two questionnaires were returned (80 percent). A majority
      (80 percent) would request routine blood tests, abdominal, and erect chest x-rays
      on arrival. Pethidine (56 percent) was the preferred analgesic, followed by
      morphine (40 percent). Ninety-four percent used an antibiotic combination of
      second/third-generation cephalosporin and metronidazole. Computerized tomography
      was the most commonly used initial investigation (42 percent). Forty percent use
      barium enema and 31 percent use a combination of barium enema and sigmoidoscopy
      as follow-up investigations. In patients older than aged 50 years, elective
      resection would be considered by a majority (51 percent) only when complications
      arose. In those aged 50 years or younger, 35 percent would resect only if
      complications arose with only 6 percent after a single episode of acute
      diverticulitis. CONCLUSIONS: There are major differences in the management of
      patients with acute diverticulitis in our current practice in one United Kingdom
      region compared with the guidelines published by The American Society of Colon
      and Rectal Surgeons, which are based on published literature. There is an urgent
      need to establish similar guidelines in the United Kingdom to improve the
      clinical outcome of patients with such a common condition.

PMID- 16897336
TI  - The influence of histopathologic criteria on the long-term prognosis of locally
      excised pT1 rectal carcinomas: results of local excision (transanal endoscopic
      microsurgery) and immediate reoperation.
AB  - PURPOSE: Local excision of early rectal cancer is a controversial issue, which is
      in part because of differences in the evaluation of histopathologic criteria.
      This prospective study was designed to determine prognostic factors for
      recurrences and the need for reoperation. METHODS: In 105 of 118 patients with
      pT1 carcinomas and local excision, results of recurrence rates and ten-year
      cancer-free survival were studied separately according to different histologic
      criteria (R0, R1, Rx, R < or = 1 mm, high-/low-risk situation), tumor
      localization (anterior, posterior, lateral wall and third of rectum), size, and
      degree of resection (full-thickness/partial wall). Patients were grouped into
      local excision (n = 89) and local excision followed by reoperation (n = 21). Risk
      classification was performed by division into "low-risk" carcinomas after local
      R0-resection (Group A) and unfavorable histologic results after local resection
      (R1, Rx, R < or = 1 mm, high-risk situation; Group B). RESULTS: Local recurrence
      rates after local R0-resection of low-risk carcinomas were 6 percent, whereas
      patients in Group B with local resection were 39 percent. The recurrence risk in
      those patients was significantly reduced to 6 percent by reoperation (P = 0.015).
      In addition, ten-year, cancer-free survival was 93 percent in Group B after
      reoperation compared with 89 percent in patients of Group A after local excision
      alone. CONCLUSIONS: Local R0-resection in cases with low-risk pT1 carcinomas
      represents an oncologically adequate therapy, which results in similar survival
      rates compared with primary radical surgery of pT1N0M0 rectal carcinomas. High
      recurrence rates are observed in tumors with unfavorable histologic result (Group
      B) requiring further treatment. In these cases immediate reoperation reduces the
      recurrence rate to 6 percent.

PMID- 16897337
TI  - Quasi-static transfer function of the rabbit middle ear' measured with a
      heterodyne interferometer with high-resolution position decoder.
AB  - Due to changes in ambient pressure and to the gas-exchange processes in the
      middle ear (ME) cavity, the ear is subject to ultra-low-frequency pressure
      variations, which are many orders of magnitude larger than the loudest acoustic
      pressures. Little quantitative data exist on how ME mechanics deals with these
      large quasi-static pressure changes and because of this lack of data, only few
      efforts could be made to incorporate quasi-static behavior into computer models.
      When designing and modeling ossicle prostheses and implantable ME hearing aids,
      the effects of large ossicle movements caused by quasi-static pressures should be
      taken into account. We investigated the response of the ME to slowly varying
      pressures by measuring the displacement of the umbo and the stapes in rabbit with
      a heterodyne interferometer with position decoder. Displacement versus pressure
      curves were obtained at linear pressure change rates between 200 Pa/s and 1.5
      kPa/s, with amplitude +/-2.5 kPa. The change in stapes position associated with a
      pressure change is independent of pressure change rate (34 microm peak-to-peak at
      +/-2.5 kPa). The stapes displacement versus pressure curves are highly nonlinear
      and level off for pressures beyond +/-1 kPa. Stapes motion shows no measurable
      hysteresis at 1.5 kPa/s, which demonstrates that the annular ligament has little
      viscoelasticity. Hysteresis increases strongly at the lowest pressure change
      rates. The stapes moves in phase with the umbo and with pressure, but the sense
      of rotation of the hysteresis loop of stapes is phase inversed. Stapes motion is
      not a simple lever ratio mimic of umbo motion, but is the consequence of complex
      changes in ossicle joints and ossicle position. The change in umbo position
      produced by a +/-2.5 kPa pressure change decreases with increasing rate from 165
      microm at 200 Pa/s to 118 microm at 1.5 kPa/s. Umbo motion already shows
      significant hysteresis at 1.5 kPa/s, but hysteresis increases further as pressure
      change rate decreases. We conclude that in the quasi-static regime, ossicle
      movement is not only governed by viscoelasticity, but that other effects become
      dominant as pressure change rate decreases below 1 kPa/s. The increasing
      hysteresis can be caused by increasing friction as speed of movement decreases,
      and incorporating speed-dependent friction coefficients will be essential to
      generate realistic models of ossicle movements at slow pressure change rates.

PMID- 16897338
TI  - Hepatic ENPP1 expression is induced in diabetic rabbits.
AB  - The ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) is an inhibitor of
      the insulin receptor. Variants of ENPP1 are associated with infantile arterial
      calcification, obesity, and insulin resistance. To study the functional relevance
      of this protein in vivo, we cloned rabbit ENPP1 and studied its regulation in
      experimentally induced diabetes mellitus. We amplified and sequenced the complete
      coding sequence of rabbit ENPP1 gene out of a liver cDNA library using redundant
      primers deduced from other species. Next, we performed quantitative PCR of ENPP1
      to study the tissue distribution of ENPP1 expression and its regulation in an
      alloxan-dependent diabetes model. The putative rabbit ENPP1 protein contains 873
      amino acids and is highly conserved when compared with human ENPP1 (90% amino
      acid identity). Particularly high levels of ENPP1 mRNA expression were found in
      adipose tissue. Quantitative PCR analysis revealed a significant upregulation of
      ENPP1 transcription in liver (p = 0.025) and brain (p = 0.034) of diabetic
      rabbits compared with controls. Hepatic ENPP1 expression is induced in diabetic
      rabbits when compared with controls. This approximately twofold upregulation of
      ENPP1 mRNA in rabbit liver parallels previous findings in patients with type 2
      diabetes mellitus. We provide further molecular information about ENPP1 as a
      potential pharmacologic target and characterize its regulation in an insulin
      dependent diabetes mellitus animal model.

PMID- 16897339
TI  - Nonrestrictive developmental regulation of microRNA gene expression.
AB  - During different periods of mammalian development, global changes in gene
      expression occur. Developmental changes in global gene expression have been
      modeled as a restrictive process. To test the restriction model of global changes
      in gene expression, we have used embryonic stem (ES) cells as a model system for
      the early mammalian embryo. ES cells are pluripotent cells that can contribute to
      all cellular lineages of the developing mammalian fetus and are derived from
      early embryonic cells. Using this model system, we have studied a new class of
      RNAs called microRNAs that have been identified and shown to play a role in the
      direct regulation of messenger RNAs. Here we report the expression signature for
      248 microRNAs in 13 independent murine ES cells, embryoid bodies, and somatic
      tissues. The expression profile for 248 mouse microRNAs was determined for
      embryonic stem cells, embryoid bodies, mouse embryos, mature heart, lung, liver,
      kidney, and brain. Characteristic microRNA expression signatures were observed
      for each evaluated sample. When the characteristic microRNA signatures for
      developmentally ordered samples were compared, immature samples exhibited a less
      complex microRNA transcript profile than did mature samples. Our data support a
      progressive model of microRNA gene expression. Based on the progressive increase
      in complexity of micro- RNA expression, we hypothesize that the mammalian
      developmental program requires a temporal coupling of expression between
      microRNAs and messenger RNAs to enable the developmental potential observed in
      mammalian ontogeny.

PMID- 16897341
TI  - Variations of eye size parameters among different strains of mice.
AB  - In the mouse, only a few genes have been definitively associated with a small-eye
      phenotype; the paired-box gene Pax6 and the gene coding for the microphthalmia
      associated transcription factor (Mitf). Mutant alleles were recovered by crude
      phenotype screens and their effects on eye size are relatively large. This
      feature points to a bias during screening for eye-size mutants, selecting
      preferentially more severe phenotypes. An unbiased method determining eye-size
      parameters in an observer-independent, quantitative manner is expected to pick up
      variations in other genes, which will be confirmed as pathologic mutations in
      confirmation crosses. The present study used optical low coherent interferometry
      (OLCI) to compare the axial eye length, the cornea and lens thicknesses, and the
      anterior chamber depth in four common wild-type, laboratory inbred strains
      (C57BL/6J, C3HeB/FeJ, 129S2/SvPasCrl, and BALB/cByJ) between 4 and 15 weeks of
      age. There were no differences between left and right eyes; differences between
      the size parameters of males and females have been observed only in a few cases.
      An optimal screening age for OLCI measurements was defined as 11 weeks of age. At
      this age, we checked two other inbred strains (AKR/J and DBA/2NCrl) as well as CD
      1 outbred mice. CD-1 mice have the largest axial length. The most impressive
      differences among inbred strains were, first, the anterior chamber depth, where
      the DBA mice have significantly lower values than the other strains. Second, the
      cornea in C3H mice is approximately 20% thicker than in the other inbred strains.
      Finally, wild-type intervals (mean +/- 3 SD) for axial length, anterior chamber
      depth, and cornea and lens thicknesses were calculated allowing a quick
      identification of pathologic outliers.

PMID- 16897342
TI  - Analysis of expansion of myeloid progenitors in mice to identify leukemic
      susceptibility genes.
AB  - The myeloid progenitor cell compartment (MPC) exhibits pronounced expansion in
      human myeloid leukemias. It is becoming more apparent that progression of
      myelodysplastic syndromes and myeloproliferative diseases to acute myelogenous
      leukemia is the result of defects in progenitor cell maturation. The MPC of bone
      marrow was analyzed in mice using a cell culture assay for measuring the relative
      frequency of proliferative myeloid progenitors. Response to the cytokines SCF, IL
      3, and GM-CSF was determined by this assay for the leukemic mouse strain BXH-2
      and ten other inbred mouse strains. Significant differences were found to exist
      among ten inbred mouse strains in the nature of their MPC in bone marrow,
      indicating the presence of genetic polymorphisms responsible for the divergence.
      The SWR/J and FVB/J strains show consistently low frequencies of myeloid
      progenitors, while the DBA/2J and SJL/J inbred strains show consistently high
      frequencies of myeloid progenitors within the bone marrow compartment. In
      addition, in silico linkage disequilibrium analysis was conducted to identify
      possible chromosomal regions responsible for the phenotypic variation. Given the
      importance of this cell compartment in leukemia progression and the soon to be
      released genomic sequence of 15 mouse strains, these differences may provide a
      valuable tool for research into leukemia.

PMID- 16897340
TI  - Artificial chromosome-based transgenes in the study of genome function.
AB  - The transfer of large DNA fragments to the mouse genome in the form of bacterial,
      yeast or phage artificial chromosomes is an important process in the definition
      of transcription units, the modeling of inherited disease states, the dissection
      of candidate regions identified by linkage analysis and the construction of in
      vivo reporter genes. However, as with small recombinant transgenes, the
      transferred sequences are usually integrated randomly often with accompanying
      genomic alterations and variable expression of the introduced genes due to the
      site of integration and/or copy number. Therefore, alternative methods of
      integrating large genomic transgenes into the genome have been developed to avoid
      the variables associated with random integration. This review encourages the
      reader to imagine the large variety of applications where artificial chromosome
      transgenes can facilitate in vivo and ex vivo studies in the mouse and provides a
      context for making the necessary decisions regarding the specifics of
      experimental design.

PMID- 16897343
TI  - No evidence for parental imprinting of mouse 22q11 gene orthologs.
AB  - Non-Mendelian factors may influence central nervous system (CNS) phenotypes in
      patients with 22q11 Deletion Syndrome (22q11DS, also known as DiGeorge or
      Velocardiofacial Syndrome), and similar mechanisms may operate in mice carrying a
      deletion of one or more 22q11 gene orthologs. Accordingly, we examined the
      influence of parent of origin on expression of 25 murine 22q11 orthologs in the
      developing and mature CNS using single nucleotide polymorphism (SNP)-based
      analysis in interspecific crosses and quantification of mRNA in a murine model of
      22q11DS. We found no evidence for absolute genomic imprinting or silencing. All
      25 genes are biallelically expressed in the developing and adult brains.
      Furthermore, if more subtle forms of allelic biasing are present, they are very
      small in magnitude and most likely beyond the resolution of currently available
      quantitative approaches. Given the high degree of similarity of human 22q11 and
      the orthologous region of mmChr16, genomic imprinting most likely cannot explain
      apparent parent-of-origin effects in 22q11DS.

PMID- 16897347
TI  - Two quantitative trait loci affecting progressive hearing loss in 101/H mice.
AB  - Although recent progress in identifying genes involved in deafness has been
      remarkable, the genetic basis of progressive hearing loss (or age-related hearing
      loss) is poorly understood because of the extreme difficulty in studying such a
      late-onset, complex disease in human populations. Several inbred strains of mice
      such as 129P1/ReJ, C57BL/6J, DBA/2J, and BALB/cByJ have been reported to exhibit
      age-related hearing loss and provide valuable models for human nonsyndromic
      progressive deafness. In this article we show that 101/H mice also exhibit
      progressive deafness with early onset. Linkage analysis of F(2) populations
      derived from crosses between the 101/H and the MAI/Pas and MBT/Pas wild-derived
      mice suggested at least two major quantitative trait loci (QTLs) that influence
      progressive hearing loss. A first QTL, designated Phl1, was mapped with a maximum
      LOD score of 6.7 to the centromeric region of Chromosome 17, where no deafness
      related QTL has been mapped so far. A second QTL, designated Phl2, mapped to
      Chromosome 10 and exhibited a maximum LOD score of 5.3. The map position of Phl2
      near the well-known QTL of age-related hearing loss (Ahl) suggested the
      possibility of allelism, although the Ahl mutation itself did not segregate in
      these crosses. Finally, we found some evidence of epistatic interaction between
      Phl1 and Phl2.

PMID- 16897345
TI  - Identification of genetic variation and putative regulatory regions in bovine
      CARD15.
AB  - Mutations in caspase recruitment domain 15 (CARD15) are associated with
      susceptibility to Crohn's disease and Blau Syndrome. We performed comparative
      analyses of the bovine, murine, and human CARD15 transcripts to elucidate
      functionality of bovine CARD15 and examine its potential role in bovine disease
      resistance. Comparative analyses of intronic sequence across seven divergent
      species were performed to identify putative regulatory element binding motifs.
      High levels of interspecies conservation in sequence, genomic structure, and
      protein domains were detected indicating common functionality for CARD15 in
      cattle, human, and mouse. We identified species-specific regulatory elements in
      the 5' and 3' untranslated regions, suggesting that modes of regulation may have
      diverged across species. Thirty-one conserved putative regulatory element binding
      motifs were identified in the CARD15 intronic sequence of seven species. To
      assess the extent of genetic diversity within bovine CARD15, 41 individuals from
      two subspecies were sequenced and screened for polymorphisms. Thirty-six single
      nucleotide polymorphisms (SNPs) were identified. Finally, 20 subspecies-specific
      haplotypes were predicted with 7 and 13 unique haplotypes explaining the
      diversity within B. taurus taurus and B. taurus indicus animals, respectively.
      Strong evidence for a simple causal relationship between these SNP loci and their
      haplotypes with Johne's disease was not detected.

PMID- 16897344
TI  - The rat prolactin gene family locus: species-specific gene family expansion.
AB  - In the rat there is a large family of paralogous genes related to prolactin
      (PRL). Members of the PRL family are expressed in cell- and temporal-specific
      patterns in the anterior pituitary, uterus, and placenta. An overriding feature
      of the PRL family is its association with pregnancy. In this investigation, we
      used information derived from the public rat genome database as a tool for
      identifying new members of the rat PRL family. The entire rat PRL gene family
      locus spans approximately 1.7 megabases (Mb) on Chromosome 17. Genes possessed
      either 5- or 6-exon organization patterns. We provide information on three newly
      identified genes orthologous to previously identified members of the mouse PRL
      gene family [placental lactogen-Ialpha (PL-Ialpha), PL-Ibeta, and proliferin
      (PLF)] and a new member of the PRL family, termed PRL-like protein-P (PLP-P).
      Information is also presented on the existence of multiple PLP-M transcripts,
      which are generated by alternative splicing. Expansion of the PRL family has
      occurred independently in rodents versus the cow and does not exist in the human
      and dog. Elucidation of the rat PRL gene family locus provides tools for studying
      the genetics and biology of the rat PRL family and new insights into species
      specific gene family expansion.

PMID- 16897346
TI  - Radiation hybrid map of the porcine genome comprising 2035 EST loci.
AB  - The IMpRH(7000-rad) radiation hybrid panel was used to map 2035 expressed
      sequence tags (ESTs) at a minimum LOD score of 4.0. A total of 134 linkage groups
      covers 57,192 cR or 78% of the predicted size of the porcine and 71% of the human
      genome, respectively. Approximately 81% (1649) of the porcine ESTs were annotated
      against the NCBI nonredundant database; 1422 mapped in silico to a location in
      build 35.1 of the human genome sequence (HGS) and 1185 to a gene and location in
      build 35.1 HGS. The map revealed 40 major breaks in synteny (1.00e (-25 )and
      lower) with the human genome, 37 of which fall within a single chromosome. At
      this improved level of resolution and coverage, porcine chromosomes (SSC) 2, 5,
      6, 7, 12, and 14 remain "gene-rich" and homologous to human chromosomes (HSA) 17,
      19, and 22, while SSC 1, 8, 11, and X have been confirmed to correspond to the
      "gene-deserts" on HSA 18, 4, 13, and X.

PMID- 16897348
TI  - Different effects of insulin and insulin-like growth factors I and II on
      osteoprogenitors and adipocyte progenitors in fetal rat bone cell populations.
AB  - We investigated the effects of insulin (1-1,000 nM), insulin-like growth factor
      (IGF)-I, and IGF-II (3-100 nM each) alone or together with 10 nM dexamethasone
      (DEX) or 10 nM 1,25-dihydroxyvitamin D(3) (1,25[OH](2)D(3)) on proliferation and
      differentiation of adipocyte and osteoblast progenitors in bone cell populations
      derived from fetal rat calvaria. The effects on differentiation were evaluated by
      counting the number of bone or osteoid nodules and adipocyte colonies and the
      effects on proliferation, by measuring their size by image analysis. The types of
      cells studied were 1,25(OH)(2)D(3)- and DEX-responsive adipocyte progenitors and
      DEX-dependent and independent osteoprogenitors. Both IGF-I and IGF-II stimulated
      osteoprogenitor differentiation both alone and in the presence of DEX, while
      insulin stimulated osteoprogenitor differentiation only in the absence of DEX.
      Neither IGF-I/-II nor insulin affected proliferation of osteoprogenitors. Insulin
      had little effect on adipocyte differentiation by itself but strongly stimulated
      differentiation in the presence of either 1,25(OH)(2)D(3) or DEX, while IGF-II
      stimulated adipocyte differentiation in both the absence and presence of
      1,25(OH)(2)D(3) or DEX. IGF-I by itself or in the presence of DEX strongly
      stimulated adipocyte cell differentiation but had little effect in the presence
      of 1,25(OH)(2)D(3). Our results demonstrate that insulin, IGF-II, and IGF-I have
      specific and different effects on the differentiation and proliferation of
      different groups of progenitor cells.

PMID- 16897349
TI  - Impact of nocturnal heartburn on quality of life, sleep, and productivity: the
      SINERGE study.
AB  - The aim of the SINERGE study was to assess the impact of nocturnal heartburn on
      quality of life, sleep, and productivity. Ambulatory patients >/=18 years old and
      classified as defined cases of nocturnal heartburn (n=337), nonnocturnal
      heartburn (n=139), uncontrolled hypertension (n=198), and symptomatic depression
      (n=104) were included in this cross-sectional study. Information on age, gender,
      body mass index, and comorbidity was collected and the following validated
      questionnaires were applied: SF-12, Pittsburgh Sleep Quality Index, and Work
      Productivity and Activity Impairment questionnaire. The prevalence of primary
      care consultation for heartburn and nocturnal heartburn was 4.7% and 1.9%,
      respectively. Health-related quality of life, sleep, and productivity were
      significantly impaired in patients with frequent nocturnal heartburn symptoms as
      compared with those of the patients without nocturnal symptoms or patients with
      hypertension. Nocturnal heartburn poses a considerable burden for the sufferer
      because of the impact on quality of life, sleep, and daily activities.

PMID- 16897350
TI  - Alcohol consumption, ART usage and high-risk sex among women infected with HIV.
AB  - We examine the role of alcohol consumption on sexual risk behavior among a cohort
      of 187 sexually active HIV-infected women (aged 18-61) in care at an urban
      ambulatory clinic in New Orleans, Louisiana, U.S. Sexual risk behavior among
      women on and off antiretroviral therapy (ART) and the relationship between
      alcohol use, ART, and behavior was also explored. One-fourth of respondents were
      classified as binge drinkers and the average number of drinking occasions per
      week ranged from none to 10-12. Approximately 60% were prescribed ART and self
      reported adherence was 90%. One-third of the women reported no condom use at last
      vaginal sex, 62% reported inconsistent condom use for vaginal sex, and 7% had
      multiple male sex partners in the last month. Binge alcohol users and women on
      ART were significantly more likely to participate in each sexual risk outcome
      examined. Partner refusal of condom use was also significantly associated with
      binge drinking patterns. Results lend strength to the equivocal literature on the
      relationship between both alcohol and prescription of ART and sexual behavior.
      Enhanced detection of alcohol abuse, coupled with risk reduction counseling
      especially among women prescribed ART are important clinical practices in
      treating women with HIV.

PMID- 16897351
TI  - Drug use and medication adherence among HIV-1 infected individuals.
AB  - This longitudinal study examined the impact of drug use and abuse on medication
      adherence among 150 HIV-infected individuals, 102 who tested urinalysis positive
      for recent illicit drug use. Medication adherence was tracked over a 6-month
      period using an electronic monitoring device (MEMS caps). Over the 6-month study
      drug-positive participants demonstrated significantly worse medication adherence
      than did drug-negative participants (63 vs. 79%, respectively). Logistic
      regression revealed that drug use was associated with over a fourfold greater
      risk of adherence failure. Stimulant users were at greatest risk for poor
      adherence. Based upon within-participants analyses comparing 3-day adherence
      rates when actively using versus not using drugs, this appears to be more a
      function of state rather than trait. These data suggest that it is the acute
      effects of intoxication, rather than stable features that may be characteristic
      of the drug-using populace, which leads to difficulties with medication
      adherence.

PMID- 16897352
TI  - Alcohol and sexuality research in the AIDS era: trends in publication activity,
      target populations and research design.
AB  - Research addressing relationships between alcohol and human sexuality has
      proliferated, due in part to efforts to characterize alcohol's role in HIV risk
      behavior. This study provides a descriptive review of the alcohol-sexuality
      literature, using abstracts from 264 identified studies to estimate changes in
      publication activity, target populations, and the prevalence of HIV-related
      studies over time. We also examine methodological trends by estimating the
      prevalence of experimental vs. non-experimental studies. Findings show
      considerable increases in research activity and diversity of populations studied
      since the mid-1980's and highlight the emergence of HIV-related studies as a
      focal point of alcohol-sexuality research efforts. Results also demonstrate a
      substantial decline in the proportion of studies utilizing experimental methods,
      in part because of frequent use of non-experimental approaches in studies of
      alcohol and HIV risk behavior. We discuss implications and review the role of
      experiments in evaluating causal relationships between alcohol and sexual risk
      behavior.

PMID- 16897353
TI  - Assessing the efficacy of a voluntary HIV counseling and testing intervention for
      pregnant women and male partners in Urumqi City, China.
AB  - This study investigated the efficacy of voluntary counseling and testing (VCT) in
      an educated cohort of pregnant women attending antenatal clinics in Urumqi,
      China. VCT was given to women and their partners (experimental group) or women
      alone (control group). Both groups were given pre- and post-intervention
      questionnaires to assess HIV knowledge and willingness to get HIV testing.
      Multivariate analysis showed that all women improved significantly in HIV
      knowledge between baseline and follow-up. Moreover, HIV knowledge was
      significantly associated with HIV testing willingness. At follow-up, women in the
      control and experimental groups were 6.8 and 7.9 times more willing to receive
      HIV testing than at baseline, respectively. VCT seems effective in this cohort of
      educated pregnant women.

PMID- 16897356
TI  - Pitch cues for the recognition of yes-no questions in French.
AB  - Linguistic studies of the intonation of Yes-No questions in French show that, in
      questions containing more than two stress groups, interrogative intonation is
      characterized by a sequence of lowered pitches or downstepped tones which precede
      the final rise. The gating paradigm was used here to determine whether subjects
      listening to French NP utterances containing three stress groups could indicate
      whether the utterance was an statement or a question before the final rise was
      heard. Although the task was difficult, findings indicate that listeners can in
      fact to a certain extent, recognize with mid confidence ratings, the intonational
      device of a question while they were hearing the downstepped tones preceding the
      final rise.

PMID- 16897357
TI  - Analysis of a Chinese phonetic compound database: implications for orthographic
      processing.
AB  - The complexity of Chinese orthography has hindered the progress of research in
      Chinese to the same level of sophistication of that in alphabetic languages such
      as English. Also, there has been no publicly available resource concerning the
      decomposition of Chinese characters, which is essential in any attempt to model
      the cognitive processes of Chinese character recognition. Here we report our
      construction and analysis of a Chinese lexical database containing the most
      frequent phonetic compounds decomposed into semantic and phonetic radicals
      according to Chinese etymology. Each radical was further decomposed into basic
      stroke patterns according to a Chinese transcription system, Cangjie (Chu, 1979
      Laboratory of chu Bong-Foo Retrieved August 25, 2004, from
      http://www.cbflabs.com/). Other information such as pronunciation and character
      frequency were also incorporated. We examine the distribution of different types
      of character, the information skew in phonetic compounds, the relations between
      subcharacter orthographic units and the pronunciation of the entire character,
      and the processing implications of these phenomena in terms of universal
      psycholinguistic principles.

PMID- 16897355
TI  - Effect of fish or soybean oil-rich diets on bradykinin, kallikrein, nitric oxide,
      leptin, corticosterone and macrophages in carrageenan stimulated rats.
AB  - We have previously demonstrated that both n-3 and n-6 polyunsaturated fatty acids
      (PUFA)-rich diets decrease the acute inflammatory response partially explained by
      the high corticosterone basal levels. The present study aimed to determine the
      effect of hyperlipidic diets (PUFA n-3 or n-6) on phagocytosis, hydrogen peroxide
      (H(2)O(2)) and nitric oxide (NO) release by macrophages, bradykinin (BK) and NO
      release in the paw inflammatory perfusate and Kallikrein (KK), corticosterone and
      leptin blood levels. Hyperlipidic diets decreased H(2)O(2) release from
      macrophages stimulated by carrageenan or phorbol-miristate-acetate (PMA), NO
      release from macrophage stimulated by carrageenan, BK and NO release in the edema
      perfusate, KK plasma levels and the increase of serum leptin after carrageenan
      stimulus. These data show that both fish and soybean oil-rich diets promote
      similar alterations on inflammatory mediators of carrageenan edema and a causal
      association with the anti-inflammatory effect of these diets.

PMID- 16897354
TI  - Interferon gamma-induced gene expression of the novel secretory phospholipase A2
      type IID in human monocyte-derived macrophages is inhibited by
      lipopolysaccharide.
AB  - Phospholipase A(2) (PLA(2)) is a superfamily of enzymes that may play a major
      role in airways inflammation. We investigated the effect of interferon-gamma (IFN
      gamma) on the gene expression of 19 different PLA(2) types in human monocyte
      derived macrophages and nasal epithelial cells (RPMI 2650). The cells were
      stimulated with IFN-gamma for different lengths of time (up to 48 h), and the
      mRNA levels of the different PLA(2) types were determined by reverse
      transcriptase-PCR (RT-PCR) and normalized to those of the house-keeping gene,
      GAPDH. It appeared that IFN-gamma clearly increased the expression of secretory
      PLA(2) IID (but not IIA) in macrophages, while both PLA(2) IID and IIA were
      upregulated in RPMI 2650 cells. Moreover, after 18 h, the mRNA levels of
      cytosolic PLA(2) IVA were 2-3 times higher in IFN-gamma-stimulated macrophages
      than controls, while there was no such effect of IFN-gamma in RPMI 2650 cells.
      Lipopolysaccharide (LPS) augmented the increased gene expression of PLA(2) IVA
      but decreased both the basal and the IFN-gamma-induced PLA(2) IID mRNA expression
      in macrophages (but not in RPMI 2650 cells). The NF-kappaB inhibitor Pyrrolidine
      dithiocarbamate (PDTC) and the phoshatidylinositol 3-kinase (PI3K) inhibitor
      wortmannin were employed to get an insight into the mechanism behind these
      observations. Incubation of macrophages with PDTC had no effect on the LPS
      impairment of PLA(2) IID gene expression, but inhibited the LPS mediated
      activation of PLA(2) IVA. No significant effect was noted of PDTC on IFN-gamma
      stimulation, while PI3K had no effect at all on any of the stimuli used.
      Furthermore, LPS (but not IFN-gamma) increased the mRNA levels of the nuclear
      factor (NF)-kappaB inhibitors alpha and xi in macrophages, but not in RPMI 2650
      cells. These findings indicate that (a) the gene expression of secretory types
      PLA(2) IID and IIA in response to IFN-gamma is much dependent on cell type, and
      (b) the regulation of PLA(2) type IID in human macrophages is clearly different
      from that of PLA(2) type IVA. (c) PLA(2) IVA is probably under control of both NF
      kappaB and IFN-gamma-responsive elements (GRE) or IFN-gamma-activating sites
      (GAS). The possibility that PLA(2) IID is involved in cytokine-mediated
      inflammation in the nasal mucosa is inferred, as is the potential role of PLA(2)
      IID in the host defense against LPS-containing bacteria.

PMID- 16897359
TI  - Games in clinical genetic counseling supervision.
AB  - Games are defined as ongoing series of complementary ulterior transactions that
      are superficially plausible but have a concealed motivation to maximize pay-offs
      and minimize penalties for the initiator. While some games are harmless and part
      of socialization, others are destructive. Destructive game-playing in clinical
      supervision, in which game-playing (initiated by either supervisors or students)
      interferes with a student's realization of internship goals, has been documented
      in some allied healthcare professions but has not yet been studied in genetic
      counseling. Genetic counselors and clinical supervisors of genetic counseling
      students were anonymously surveyed regarding their experiences with destructive
      game-playing. Results show that such games do occur in genetic counseling
      clinical supervision. Some games are the same or similar to ones previously
      described in other health-care professions; others may be unique to genetic
      counseling. The purpose of this paper is to document these games as a first step
      to facilitating dialogue, understanding and awareness of them.

PMID- 16897360
TI  - Correlates of depressive symptoms among women seeking cancer genetic counseling
      and risk assessment at a high-risk cancer clinic.
AB  - The aims of this study were to (1) assess the level of depression among women
      seeking cancer genetic counseling and risk assessment and to (2) identify and
      describe the demographic, health history, and health behavior correlates of
      clinically significant depression. Participants were 280 women presenting for an
      intake appointment at a university cancer risk clinic. During intake,
      participants completed questionnaires assessing demographics, health history,
      health practices, and depression. Twenty-eight percent of the sample met criteria
      for at least mild depression. Descriptive statistics indicated that depressed
      women were more likely to be African American, to have more children, less likely
      to receive a mammogram, and consumed fewer alcoholic drinks per week than
      nondepressed women. Given the known associations between depression, health
      behaviors such as cancer screening, and potential responses to the genetic
      testing process, assessment of mood disturbance remains an important
      consideration for genetic counselors.

PMID- 16897361
TI  - Endothelin signaling pathways in rat adrenal medulla.
AB  - 1. We further characterized the effect of endothelins (ETs) on receptor-mediated
      phosphoinositide (PI) turnover, nitric oxide synthase (NOS) activation, and cGMP
      formation in whole rat adrenal medulla. 2. The PI hydrolysis was assessed as
      accumulation of inositol monophosphates (InsP(1)) in the presence of 10 mM LiCl
      in whole tissue and the analysis of inositol-1-phosphate by Dowex anion exchange
      chromatography. NOS activity was assayed by monitoring the conversion of
      radiolabeled L-arginine to L-citrulline. Cyclic GMP formation was assessed as
      accumulation of cGMP in whole tissue in the presence of phosphodiesterase
      inhibition, and the amount of cGMP formed was determined by radioimmuno-antibody
      procedure. 3. ET-1 and ET-3 increased PI turnover by 30% in whole adrenal medulla
      prelabeled with [(3)H] myoinositol. Both ETs isoforms, at equimolar doses,
      increased NOS activity and cGMP levels in similar degree. The selective ET(B)
      receptor agonist, IRL-1620, also increased cGMP formation, mimicking the effects
      of ETs, while IRL-1620 did not alter the PI metabolism. ETs-induced InsP(1)
      accumulation and cGMP was dependent on extracellular calcium. The effect of ETs
      on PI turnover was inhibited by neomycin. The L-arginine analogue, N-nitro-L
      arginine (L-NAME), and two inhibitors of soluble guanylyl cyclase, methylene blue
      and ODQ, significantly inhibited the increase in cGMP production induced by ETs
      or IRL-1620. The selective ET(A) receptor antagonist, BQ 123, inhibited the ETs
      induced increase in PI turnover, while the selective ET(B) receptor antagonist,
      BQ 788, was ineffective. Likewise, BQ 788, significantly inhibited ET-1- or ET-3
      induced NOS activation and cGMP generation but not ETs-induced InsP(1)
      accumulation. 4. Our data indicate that stimulation of PI turnover and NO-induced
      cGMP generation constitutes ETs signaling pathways in rat adrenal medulla. The
      former action is mediated through activation of ET(A) receptor, while the latter
      through the activation of ET(B) receptor. These results support the role of
      endothelins in the regulation of adrenal medulla function.

PMID- 16897362
TI  - Centrally acting imidazolines stimulate vascular alpha 1A-adrenergic receptors in
      Rat-Tail Artery.
AB  - : 1. Centrally acting imidazoline antihypertensive agents clonidine and
      moxonidine also act peripherally to contract blood vessels. While these agents
      act at both I(1)-imidazoline and alpha 2 adrenergic receptors centrally, the
      receptor types by which they mediate contraction require further definition. We
      therefore characterized the receptor subtype by which these agents mediate
      contraction of proximal rat-tail artery. 2. Dose-response curves were determined
      for phenylephrine and for several imidazoline ligands, using endothelium denuded,
      isolated ring segments, of tail arteries from adult male Sprague-Dawley rats.
      Ring segments were mounted on a force transducer with platinum wires and immersed
      in a tissue bath containing Krebs solution, to which drugs could be added.
      Signals were digitized and recorded by a computer. 3. Tail artery contractions
      expressed as a percent of contraction to 106 mM potassium were phenylephrine
      (96%), moxonidine (88%), clonidine (52%), and UK14304 (30%). Neither rilmenidine
      nor harmane caused contraction. Contraction of tail artery to moxonidine or
      clonidine could be blocked by alpha 1 antagonist urapidil or prazosin, and also
      by alpha 1A subtype selective antagonist WB4101. Schild plots were generated and
      a calculated pA2 value of 9.2 for prazosin in the presence of clonidine confirms
      clonidine as an agonist at alpha 1A receptors in proximal segments of rat-tail
      artery. 4. Our work suggests that clonidine and moxonidine are promiscuous
      compounds at micromolar concentrations and that harmane and rilmenidine are more
      selective compounds for in vivo imidazoline research.

PMID- 16897363
TI  - Giant cells: contradiction to two-hit model of tuber formation?
AB  - Tuberous sclerosis (TSC) is an autosomal dominant disease characterized by the
      formation of hamartomatous lesions in many organs, including brain, heart or
      kidneys. It has been found that TSC is caused by the mutation in one of the two
      tumor suppressor genes: TSC1 or TSC2, encoding hamartin and tuberin,
      respectively. According to Knudson's two-hit model of tumorigenesis, second-hit
      mutation and resulting loss of heterozygosity (LOH) of a tumor suppressor gene is
      necessary for tumor formation. In fact, LOH is commonly found in several types of
      hamartomas formed in the process of tuberous sclerosis, but, interestingly, not
      in brain lesions, containing characteristic giant cells. In this paper, we review
      literature covering origination of giant cells and present several hypotheses
      explaining why in spite of the presence of hamartin and tuberin, brain lesions
      form in TSC patients.

PMID- 16897364
TI  - Concentration of nucleosides and related compounds in cerebral and cerebellar
      cortical areas and white matter of the human brain.
AB  - 1. Nucleosides potentially participate in the neuronal functions of the brain.
      However, their distribution and changes in their concentrations in the human
      brain is not known. For better understanding of nucleoside functions, changes of
      nucleoside concentrations by age and a complete map of nucleoside levels in the
      human brain are actual requirements. 2. We used post mortem human brain samples
      in the experiments and applied a recently modified HPLC method for the
      measurement of nucleosides. To estimate concentrations and patterns of
      nucleosides in alive human brain we used a recently developed reverse
      extrapolation method and multivariate statistical analyses. 3. We analyzed four
      nucleosides and three nucleobases in human cerebellar, cerebral cortices and in
      white matter in young and old adults. Average concentrations of the 308 samples
      investigated (mean+/-SEM) were the following (pmol/mg wet tissue weight):
      adenosine 10.3+/-0.6, inosine 69.5+/-1.7, guanosine 13.5+/-0.4, uridine 52.4+/
      1.2, uracil 8.4+/-0.3, hypoxanthine 108.6+/-2.0 and xanthine 54.8+/-1.3. We also
      demonstrated that concentrations of inosine and adenosine in the cerebral cortex
      and guanosine in the cerebral white matter are age-dependent. 4. Using
      multivariate statistical analyses and degradation coefficients, we present an
      uneven regional distribution of nucleosides in the human brain. The methods
      presented here allow to creation of a nucleoside map of the human brain by
      measuring the concentration of nucleosides in microdissected tissue samples. Our
      data support a functional role for nucleosides in the brain.

PMID- 16897365
TI  - Electrophysiological effects of three groups of glutamate metabotropic receptors
      in rat piriform cortex.
AB  - 1. The effects of three metabotropic glutamate receptor (mGluR) agonists were
      tested in two pathways of rat piriform cortex. The group I, II and III mGluR
      agonists used were RS-3,5-dihydroxyphenenylglycine (DHPG) (10-100 microM),
      (2S,1'S,2'S)-2-Carboxycyclopropyl (L-CCG) (20-100 microM) and L(+)-2-amino-4
      phosphonobutyric acid (L-AP4) (5-500 microM), respectively. 2. The effects of the
      three groups of agonists on synaptic transmission in the two piriform cortex
      pathways also were examined. All three agonists reduced the amplitude of the
      monosynaptic EPSPs generated by stimulation of the lateral olfactory tract (LOT)
      or of the association fiber pathway (ASSN). This was always accompanied by an
      increase in paired pulse facilitation. 3. Group I and II mGluR agonists had
      similar synaptic effects on the two pathways, while the group III mGluR agonist
      suppressed the LOT pathway more than the association pathway. 4. The group II and
      III mGluR agonists had no effect on passive membrane properties of pyramidal
      neurons. Group I agonists depolarized the pyramidal neuron membrane potential,
      and enhanced both membrane resistance and noise. 5. Our data suggest that all
      three types of mGluRs modulate synaptic transmission in both of these pathways in
      piriform cortex. Only group I agonists alter post-synaptic membrane properties,
      while all three types of receptor regulate synaptic transmission. Groups I and II
      are equally potent in the LOT and association fiber pathways, while group III
      receptors are more potent in the LOT than the association fiber pathways.

PMID- 16897366
TI  - Transplants of human mesenchymal stem cells improve functional recovery after
      spinal cord injury in the rat.
AB  - Human mesenchymal stem cells (hMSCs) derived from adult bone marrow represent a
      potentially useful source of cells for cell replacement therapy after nervous
      tissue damage. They can be expanded in culture and reintroduced into patients as
      autografts or allografts with unique immunologic properties. The aim of the
      present study was to investigate (i) survival, migration, differentiation
      properties of hMSCs transplanted into non-immunosuppressed rats after spinal cord
      injury (SCI) and (ii) impact of hMSC transplantation on functional recovery.
      Seven days after SCI, rats received i.v. injection of hMSCs (2x10(6) in 0.5 mL
      DMEM) isolated from adult healthy donors. Functional recovery was assessed by
      Basso-Beattie-Bresnahan (BBB) score weekly for 28 days. Our results showed
      gradual improvement of locomotor function in transplanted rats with statistically
      significant differences at 21 and 28 days. Immunocytochemical analysis using
      human nuclei (NUMA) and BrdU antibodies confirmed survival and migration of hMSCs
      into the injury site. Transplanted cells were found to infiltrate mainly into the
      ventrolateral white matter tracts, spreading also to adjacent segments located
      rostro-caudaly to the injury epicenter. In double-stained preparations, hMSCs
      were found to differentiate into oligodendrocytes (APC), but not into cells
      expressing neuronal markers (NeuN). Accumulation of GAP-43 regrowing axons within
      damaged white matter tracts after transplantation was observed. Our findings
      indicate that hMSCs may facilitate recovery from spinal cord injury by
      remyelinating spared white matter tracts and/or by enhancing axonal growth. In
      addition, low immunogenicity of hMSCs was confirmed by survival of donor cells
      without immunosuppressive treatment.

PMID- 16897370
TI  - Preconception brief: occupational/environmental exposures.
AB  - In the last decade, more than half of U.S. children were born to working mothers
      and 65% of working men and women were of reproductive age. In 2004 more than 28
      million women age 18-44 were employed full time. This implies the need for
      clinicians to possess an awareness about the impact of work on the health of
      their patients and their future offspring. Most chemicals in the workplace have
      not been evaluated for reproductive toxicity, and where exposure limits do exist,
      they were generally not designed to mitigate reproductive risk. Therefore, many
      toxicants with unambiguous reproductive and developmental effects are still in
      regular commercial or therapeutic use and thus present exposure potential to
      workers. Examples of these include heavy metals, (lead, cadmium), organic
      solvents (glycol ethers, percholoroethylene), pesticides and herbicides (ethylene
      dibromide) and sterilants, anesthetic gases and anti-cancer drugs used in
      healthcare. Surprisingly, many of these reproductive toxicants are well
      represented in traditional employment sectors of women, such as healthcare and
      cosmetology. Environmental exposures also figure prominently in evaluating a
      woman's health risk and that to a pregnancy. Food and water quality and pesticide
      and solvent usage are increasingly topics raised by women and men contemplating
      pregnancy. The microenvironment of a woman, such as her choices of hobbies and
      leisure time activities also come into play. Caregivers must be aware of their
      patients' potential environmental and workplace exposures and weigh any risk of
      exposure in the context of the time-dependent window of reproductive
      susceptibility. This will allow informed decision-making about the need for
      changes in behavior, diet, hobbies or the need for added protections on the job
      or alternative duty assignment. Examples of such environmental and occupational
      history elements will be presented together with counseling strategies for the
      clinician.

PMID- 16897368
TI  - The effect of endurance training on regional serotonin metabolism in the brain
      during early stage of detraining period in the female rat.
AB  - 1. The effect was examined of a single bout of nonexhaustive endurance exercise
      on tryptophan (Try), serotonin (5-HT), 5-hydroxyindolacetic acid (5-HIAA), and
      tryptophan hydroxylase (TpH) levels in different parts of rat brain (brain
      cortex, cerebellum, hypothalamus, midbrain striatum, medulla) on the last day of
      endurance training and 48 h later (detraining period). 2. Female rats were
      subjected to a 6-week endurance training programme. The effectiveness of the
      training was evaluated by measuring anaerobic threshold (AT). High performance
      liquid chromatography (HPLC) was used to determine regional Try, 5-HT, and 5-HIAA
      contents in the brain, and thin layer chromatography followed by gas-liquid
      chromatography was used to determine blood levels of free fatty acids. Regional
      TpH levels were measured by Western blot analysis. 3. In the two rat groups
      subjected to endurance training, in all brain regions studied but cerebellum, 5
      HT content was significantly lower after the last bout of nonexhaustive endurance
      exercise than in resting control rats that were not subjected to the training.
      Similarly, the cortical and striatal, but not cerebellar, 5-HT/Try ratios were
      significantly lower in the trained rats at the end of the last training session
      and at the end of a single bout of nonexhaustive exercise administered after a 48
      h detraining period than in the controls. TpH protein level was decreased by 15
      25% after the last bout of exercise either during the training process or after
      the and 1 h bout of endurance exercise performed 48 h after cessation of
      endurance training in brain cortex and striatum but not cerebellar.4. These
      results indicate that the reduction in 5-HT level was the adaptive response to
      endurance training. The lowered 5-HT/Try ratio and lowered TpH protein level
      attained after the training process suggests and that this change may be, at
      least partially, attributed to downregulation of TpH activity.

PMID- 16897373
TI  - Treatment of tobacco use in preconception care.

PMID- 16897369
TI  - The onset of brain injury and neurodegeneration triggers the synthesis of
      docosanoid neuroprotective signaling.
AB  - Bioactive lipid messengers are formed through phospholipase-mediated cleavage of
      specific phospholipids from membrane reservoirs. Effectors that activate the
      synthesis of lipid messengers, include ion channels, neurotransmitters, membrane
      depolarization, cytokines, and neurotrophic factors. In turn, lipid messengers
      regulate and interact with multiple pathways, participating in the development,
      differentiation, function (e.g., long-term potentiation and memory), protection,
      and repair of cells of the nervous system. Overall, bioactive lipids participate
      in the regulation of synaptic function and dysfunction. Platelet-activating
      factor (PAF) and COX-2-synthesized PGE(2) modulate synaptic plasticity and
      memory. Oxidative stress disrupts lipid signaling, fosters lipid peroxidation,
      and initiates and propagates neurodegeneration. Lipid messengers participate in
      the interactions among neurons, astrocytes, oligodendrocytes, microglia, cells of
      the microvasculature, and other cells. A conglomerate of interrelated cells
      comprises the neurovascular unit. Signaling at the neurovascular unit is clearly
      altered in the early stages of cerebrovascular disease as well as in
      neurodegenerations. Here we will provide examples of how signaling by lipids
      regulates critical events essential for neuronal survival. We will highlight a
      newly identified, DHA-derived messenger, neuroprotectin D1, which attenuates
      oxidative stress-induced apoptosis. The specificity and potency of this novel
      docosanoid (neuroprotectin D1) indicate a potentially important target for
      therapeutic intervention.

PMID- 16897374
TI  - Do we practice what we preach? A review of actual clinical practice with regards
      to preconception care guidelines.
AB  - OBJECTIVES: To review what past studies have found with regard to existing
      clinical practices and approaches to providing preconception care. METHODS: A
      literature review between 1966 and September 2005 was performed using Medline.
      Key words included preconception care, preconception counseling, preconception
      surveys, practice patterns, pregnancy outcomes, prepregnancy planning, and
      prepregnancy surveys. RESULTS: There are no current national recommendations that
      fully address preconception care; as a result, there is wide variability in what
      is provided clinically under the rubric of preconception care. CONCLUSIONS: In
      2005, the Centers for Disease Control and Prevention sponsored a national summit
      regarding preconception care and efforts are underway to develop a uniform set of
      national recommendations and guidelines for preconception care. Understanding how
      preconception care is presently incorporated and manifested in current medical
      practices should help in the development of these national guidelines. Knowing
      where, how, and why some specific preconception recommendations have been
      successfully adopted and translated into clinical practice, as well as barriers
      to implementation of other recommendations or guidelines, is vitally important in
      developing an overarching set of national guidelines. Ultimately, the success of
      these recommendations rests on their ability to influence and shape women's
      health policy.

PMID- 16897375
TI  - Using video modeling to teach complex social sequences to children with autism.
AB  - This study comprised of two experiments was designed to teach complex social
      sequences to children with autism. Experimental control was achieved by
      collecting data using means of within-system design methodology. Across a number
      of conditions children were taken to a room to view one of the four short videos
      of two people engaging in a simple sequence of activities. Then, each child's
      behavior was assessed in the same room. Results showed that this video modeling
      procedure enhanced the social initiation skills of all children. It also
      facilitated reciprocal play engagement and imitative responding of a sequence of
      behaviors, in which social initiation was not included. These behavior changes
      generalized across peers and maintained after a 1- and 2-month follow-up period.

PMID- 16897377
TI  - Differentiating between autism spectrum disorders and other developmental
      disabilities in children who failed a screening instrument for ASD.
AB  - This study compared behavioral presentation of toddlers with autistic spectrum
      disorders (ASD) and toddlers with global developmental delay (DD) or
      developmental language disorder (DLD) who display some characteristics of ASD
      using the diagnostic algorithm items from the Autism Diagnostic Observation
      Schedule, Generic (ADOS), the Childhood Autism Rating Scale (CARS), and Modified
      Checklist for Autism in Toddlers (M-CHAT). To date, 195 children have failed the
      M-CHAT and have been diagnosed with ASD, DD or DLD. Children with ASD had
      prominent and consistent impairments in socialization skills, especially joint
      attention skills and were more impaired in some aspects of communication, play,
      and sensory processing. Children with ASD and children with DD/DLD shared common
      features, but certain behavioral markers differentiated the two groups.

PMID- 16897376
TI  - Studying the emergence of autism spectrum disorders in high-risk infants:
      methodological and practical issues.
AB  - Detecting early signs of autism is essential for timely diagnosis and initiation
      of effective interventions. Several research groups have initiated prospective
      studies of high-risk populations including infant siblings, to systematically
      collect data on early signs within a longitudinal design. Despite the potential
      advantages of prospective studies of young children at high-risk for autism,
      there are also significant methodological, ethical and practical challenges. This
      paper outlines several of these challenges, including those related to sampling
      (e.g., defining appropriate comparison groups), measurement and clinical
      implications (e.g., addressing the needs of infants suspected of having early
      signs). We suggest possible design and implementation strategies to address these
      various challenges, based on current research efforts in the field and previous
      studies involving high-risk populations.

PMID- 16897378
TI  - Physical illness, pain, and problem behavior in minimally verbal people with
      developmental disabilities.
AB  - There is growing interest in the role that physical illness and pain might play
      in exacerbating problem behavior in individuals with developmental disabilities.
      Assessment of these factors, however, is often difficult since many individuals
      have minimal verbal communication skills. In response to this difficulty, we
      developed a sequential method of assessment involving retrospective and
      prospective measurement strategies. We found that the frequency and intensity of
      problem behavior was greater on "sick" days than on "well" days. Further, the
      higher the level of pain, the greater was the frequency and intensity of problem
      behavior. We discuss the concept of pain as a setting event for problem behavior
      and the intervention strategies that follow from this conceptualization.

PMID- 16897379
TI  - Short breaks services for children with autistic spectrum disorders: factors
      associated with service use and non-use.
AB  - Short break services in a UK county were studied using a postal survey of 256
      families with a child with an autistic spectrum disorder (ASD). Results confirmed
      high degrees of stress and low levels of informal support for all families, but
      no significant difference in the informal support available to non-users as
      compared to users of short break services. Robinson & Stalker's (1990) 10-point
      dependency scale showed a significant difference in dependence and more difficult
      behaviors between children of users and non-users. However, a large number of non
      users had children with high dependence (scoring >7 points). Access was denied by
      the age of the child (under 11) diagnosis (Asperger syndrome), educational
      placement (mainstream) and lack of social worker referral.

PMID- 16897380
TI  - Designing research studies on psychosocial interventions in autism.
AB  - To address methodological challenges in research on psychosocial interventions
      for autism spectrum disorder (ASD), a model was developed for systematically
      validating and disseminating interventions in a sequence of steps. First, initial
      efficacy studies are conducted to establish interventions as promising. Next,
      promising interventions are assembled into a manual, which undergoes pilot
      testing. Then, randomized clinical trials test efficacy under controlled
      conditions. Finally, effectiveness studies evaluate outcomes in community
      settings. Guidelines for research designs at each step are presented. Based on
      the model, current priorities in ASD research include (a) preparation for
      efficacy and effectiveness trials by developing manuals for interventions that
      have shown promise and (b) initial efficacy studies on interventions for core
      features of ASD such as social reciprocity.

PMID- 16897381
TI  - Atypical categorical perception in autism: autonomy of discrimination?
AB  - A diminished top-down influence has been proposed in autism, to account for
      enhanced performance in low-level perceptual tasks. Applied to perceptual
      categorization, this hypothesis predicts a diminished influence of category on
      discrimination. In order to test this hypothesis, we compared categorical
      perception in 16 individuals with and 16 individuals without high-functioning
      autism. While participants with and without autism displayed a typical
      classification curve, there was no facilitation of discrimination near the
      category boundary in the autism group. The absence of influence of categorical
      knowledge on discrimination suggests an increased autonomy of low-level
      perceptual processes in autism, in the form of a reduced top-down influence from
      categories toward discrimination.

PMID- 16897382
TI  - Sorting preference in children with autism: the dominance of concrete features.
AB  - The current study investigates preference to sort objects on the basis of either
      concrete or abstract features in children with and without autism. Participants
      were asked to sort a set of books into two groups that could be differentiated
      according to concrete (color, size) or abstract criteria (category membership:
      sports/games). The results showed that those with autism, unlike controls, were
      significantly more likely to sort according to a concrete criterion. In a further
      phase of testing, those with autism still did not sort according to abstract
      criteria, even when this was the only basis for sorting systematically. The
      findings are interpreted as evidence for a preference in autism to process
      concrete over abstract features of stimuli.

PMID- 16897383
TI  - A case-control study of personality style and psychopathology in parents of
      subjects with autism.
AB  - To probe the specificity of traits that might be conceptualised as the broader
      phenotype of autism, parents of subjects with autism from simplex and multiplex
      families as well as parents of subjects with obsessive-compulsive disorders
      (OCD), early onset schizophrenia (EOS) and mental retardation (MR) were assessed
      using the Personality Style and Disorder Inventory and the Symptom Checklist-90
      Revised. Autism parents' scores were increased on several subscales (e.g.
      reserved/schizoid, depression) compared to parents of subjects with OCD, EOS and
      normative data, but not in comparison to MR parents. Results provide some support
      for the specificity of the broader phenotype of autism. The burden of raising
      severely disabled children could not be ruled out as a factor influencing parts
      of this phenotype.

PMID- 16897384
TI  - Cognitive and verbal abilities of 24- to 36-month-old siblings of children with
      autism.
AB  - The cognitive and language skills of 30 siblings of children with autism (SIBS-A)
      and 30 siblings of typically developing children (SIBS-TD) were compared. Non
      significant group differences emerged for cognition at both ages. At 24 months,
      significantly more SIBS-A demonstrated language scores one or two standard
      deviations below the mean compared to SIBS-TD. At 36 months, the groups differed
      significantly in receptive language, and more SIBS-A displayed receptive and
      expressive difficulties compared to SIBS-TD. Six SIBS-A (including one diagnosed
      with autism) revealed language scores more than two standard deviations below the
      mean at both ages, a pattern not seen in the SIBS-TD. Results are discussed in
      reference to language difficulties in autism spectrum disorders and the genetic
      liability for autism.

PMID- 16897385
TI  - Initial characteristics of psychological development and evolution of the young
      autistic child.
AB  - This longitudinal study assessed multidisciplinary data on 219 children with
      autistic spectrum disorders from the median age of 5 (Time 1) to 8 years old
      (Time 2). The evolution of psychological and adaptive data was subjected to
      cluster analysis. Four clinically meaningful clusters emerged. The first group
      (21%) demonstrated the most important psychological transformations between the
      two times of the research. The second group (24%) made progress but less than
      group 1. The third and biggest group (30%) kept the same developmental slope. The
      fourth group (25%) showed no significant evolution between the two times of the
      research. This study highlights important differences among children with autism
      and the necessity of using a developmental view when considering the autistic
      syndrome.

PMID- 16897387
TI  - Behavioral and emotional problems in young people with pervasive developmental
      disorders: relative prevalence, effects of subject characteristics, and empirical
      classification.
AB  - Parents or teachers rated 487 non-clinically referred young people with Pervasive
      Developmental Disorders on the Nisonger Child Behavior Rating Form. The
      objectives of the study were to examine the relative prevalence of specific
      behavior problems, assess the impact of subject characteristics, and derive an
      empirical classification of behavioral and emotional problems for this
      population. Results indicated that the youngsters experienced high rates of
      behavior and emotional problems. Cluster analysis suggested that six- and eight
      cluster solutions best fit the ratings provided by parents and teachers,
      respectively. Both parent and teacher cluster solutions contained groups of
      children characterized as problem free, well adapted, hyperactive, anxious, and
      with undifferentiated behavior disturbances. The empirically derived clusters
      were supported by data external to the analyses.

PMID- 16897386
TI  - Rules versus prototype matching: strategies of perception of emotional facial
      expressions in the autism spectrum.
AB  - When perceiving emotional facial expressions, people with autistic spectrum
      disorders (ASD) appear to focus on individual facial features rather than
      configurations. This paper tests whether individuals with ASD use these features
      in a rule-based strategy of emotional perception, rather than a typical, template
      based strategy by considering outcome implications of these strategies. Rule
      based strategies are more tolerant of extreme stimuli than are template-based
      ones. Tolerance for exaggerated emotional facial expressions in individuals with
      ASD compared to IQ and education matched controls was tested in a forced-choice
      paradigm. For five of six emotions, those with ASD were more likely to accept the
      most exaggerated images as most realistic. People with ASD appear to rely more
      heavily on a rule-based strategy than a template-based strategy in perceiving
      emotional facial expressions.

PMID- 16897388
TI  - Verbal marking of affect by children with Asperger Syndrome and high functioning
      autism during spontaneous interactions with family members.
AB  - Verbal marking of affect by older children with Asperger Syndrome (AS) and high
      functioning autism (HFA) during spontaneous interactions is described. Discourse
      analysis of AS and HFA and typically developing children included frequency of
      affective utterances, affective initiations, affective labels and affective
      explanations, attribution of affective responses to self and others, and positive
      and negative markers of affect. Findings indicate that children with AS and HFA
      engaged in a higher proportion of affect marking and provided a higher proportion
      of affective explanations than typically developing children, yet were less
      likely to initiate affect marking sequences or talk about the affective responses
      of others. No significant differences were found between groups in terms of the
      marking of positive and negative affect.

PMID- 16897389
TI  - Maternal recurrent mood disorders and high-functioning autism.
AB  - A quantitative examination was made of the association of parental mood and
      anxiety disorders with severity of disability within a large sample of young
      children with Pervasive Developmental Disorder (PDD). Maternal recurrent mood
      disorders were associated with elevated cognitive and adaptive functioning in
      their affected children, parent reports of increased behavior problems and
      teacher reports of an internalizing behavioral style. Maternal histories of
      anxiety disorders and paternal depression or anxiety disorders were not
      associated with levels of adaptive/cognitive functioning or levels of maladaptive
      behaviors in the children. Various genetic models are discussed. It is
      hypothesized that genes associated with recurrent depression in women may exert a
      "protective" effect on cognition and adaptive functioning in children with PDD.

PMID- 16897391
TI  - Fragmented visuospatial processing in children with pervasive developmental
      disorder.
AB  - Children diagnosed with Pervasive Developmental Disorder Not Otherwise Specified
      (PDD-NOS) and Asperger Syndrome (AS) may be characterised by a similar perceptual
      focus on details as children with autistic disorder (AD). This was tested by
      analysing their performance in a visuoperceptual task [the Children's Embedded
      Figure Test (CEFT)] and a graphic reproduction task [the Rey Complex Figure Task
      (Rey CFT)]. Control groups were children with Tourette Syndrome (TS) and
      typically developing children. The TS sample performed similarly to the normal
      control group in both tasks. The CEFT results did not show the expected
      preference for local processing in children with PDD-NOS. However, the Rey CFT
      data revealed that the children with this lesser variant of PDD processed
      visuospatial information in a fragmented way and were deficient in global
      processing.

PMID- 16897390
TI  - Etiologies of autism in a case-series from Tanzania.
AB  - Most autism has a genetic cause although post-encephalitis cases are reported. In
      a case-series (N = 20) from Tanzania, 14 met research criteria for autism. Three
      (M:F = 1:2) had normal development to age 22, 35, and 42 months, with onset of
      autism upon recovery from severe malaria, attended by prolonged high fever,
      convulsions, and in one case prolonged loss of consciousness. In four other cases
      (M:F = 3:1), the temporal relationship between onset of autism and severe
      infection was close, but possibly spurious since malaria is common in Tanzania
      and there were indications of abnormal development in the child or a family
      member. In seven cases, (M:F = 6:1) autism onset was unrelated to malaria. The
      excess of non-verbal cases (N = 10) is related local diagnostic practice.

PMID- 16897393
TI  - Brief report: Use of DQ for estimating cognitive ability in young children with
      autism.
AB  - The utility of Developmental Quotients (DQ) from the Psychoeducational Profile
      Revised (PEP-R) to estimate cognitive ability in young children with autism was
      assessed. DQ scores were compared to scores from the Stanford-Binet Intelligence
      Scales-Fourth Edition (SB-FE) for 27 preschool students with autism. Overall and
      domain DQ's on the PEP-R were significantly correlated with SB-FE composite IQ
      and Verbal Reasoning scores. Additional analyses with rank scores from each
      instrument confirmed these results. Results indicate that DQ scores obtained by
      the PEP-R are reasonable estimates of cognitive ability in this sample as
      measured by the SB-FE. Some administration advantages suggest that the PEP-R may
      be a viable alternative to the SB-FE (for estimating cognitive skills) under some
      conditions.

PMID- 16897392
TI  - The perception of animacy in young children with autism.
AB  - Visual perception may be a developmental prerequisite to some types of social
      understanding. The ability to perceive social information given visual motion
      appears to develop early. However, children with autism have profound deficits in
      social cognitive function and may fail to see social motion in the same way that
      typically developing children do. We tested the hypothesis that children with
      autism fail to discriminate animate motion, using a novel paradigm involving
      simple geometric figures. The subjects were 23 children with autism (c.a. 70.7
      mos.), 18 children with other developmental disabilities (c.a. 68.2 mos.), and 18
      typically developing children (c.a. 46.4 mos.). Children saw two circles moving
      on a screen and were rewarded for identifying the one that moved as if animate. A
      control condition required children to identify the heavier of two objects.
      Children with autism initially showed a deficit in categorizing objects as
      animate (though no deficit on the control task), but showed no deficit in this
      ability after they had reached criterion in the training phase. These results are
      discussed in terms of the social orienting theory of autism, and the possibility
      that animacy perception might be preserved in autism, even if it is not used
      automatically.

PMID- 16897394
TI  - Social escape behaviors in children with fragile X syndrome.
AB  - Social escape behavior is a common behavioral feature of individuals with fragile
      X syndrome (fraX). In this observational study, we examined the effect of
      antecedent social and performance demands on problem behaviors in four
      conditions: face-to-face interview, silent reading, oral reading and a singing
      task. Results showed that problem behaviors were significantly more likely to
      occur during the interview and singing conditions. Higher levels of salivary
      cortisol were predictive of higher levels of fidgeting behavior and lower levels
      of eye contact in male participants. There were no associations between level of
      FMRP expression and social escape behaviors. These data suggest that specific
      antecedent biological and environmental factors evoke social escape behaviors in
      fragile X syndrome.

PMID- 16897395
TI  - Patterns of complementary and alternative medical therapy use in children
      diagnosed with autism spectrum disorders.
AB  - Previous studies suggest that complementary and alternative medical (CAM) therapy
      use in children with chronic illnesses is higher than in children in the general
      population. In this study, we investigated patterns of CAM therapy use in
      children diagnosed with autism spectrum disorders (ASD, n = 50) as compared to a
      control population of children with no ASD (n = 50). Over half of the parents in
      the ASD group reported using, or had used at least one CAM therapy for their
      child (52%) as compared to 28% of the control group (P = 0.024). Seventy percent
      of therapies used in the ASD group were biologically based therapies comprised of
      special diets or supplements, and parents felt that 75% of the therapies used
      were beneficial.

PMID- 16897396
TI  - Patterns of reading ability in children with autism spectrum disorder.
AB  - This study investigated reading skills in 41 children with autism spectrum
      disorder. Four components of reading skill were assessed: word recognition,
      nonword decoding, text reading accuracy and text comprehension. Overall, levels
      of word and nonword reading and text reading accuracy fell within average range
      although reading comprehension was impaired. However, there was considerable
      variability across the sample with performance on most tests ranging from floor
      to ceiling levels. Some children read accurately but showed very poor
      comprehension, consistent with a hyperlexia reading profile; some children were
      poor at reading words and nonwords whereas others were unable to decode nonwords,
      despite a reasonable level of word reading skill. These findings demonstrate the
      heterogeneous nature of reading skills in children with ASD.

PMID- 16897397
TI  - Assessing need for social support in parents of children with autism and Down
      syndrome.
AB  - Parents of children with autism frequently turn to the service delivery system to
      access supports designed to help adapt to the challenges of having a child with a
      life-long impairment. Although studies have suggested various supports and coping
      strategies that are effective for adapting, few studies have examined parents'
      own perceptions of needs, and whether parents felt their needs were being met. In
      the present study the Family Needs Questionnaire (FNQ; Waaland et al., 1993) was
      modified to address needs for children with developmental disorders. A sample of
      fifty-six parents of children with autism and a comparison group of thirty-two
      parents of children with Down syndrome completed the FNQ. The groups did not
      differ significantly on the number of important needs reported nor the number of
      important needs being met. However, the two groups differed in the types of
      supports they most frequently endorsed as Important or Unmet.

PMID- 16897398
TI  - Agreement among four diagnostic instruments for autism spectrum disorders in
      toddlers.
AB  - Autistic spectrum disorders (ASD) can be difficult to diagnose in toddlers. This
      study compared diagnostic measures (ADOS-G, ADI-R, CARS, and clinical judgment
      using DSM-IV criteria) applied to toddlers. Results indicated that the ADOS-G,
      CARS, and clinical judgment agreed with each other but not with the ADI-R. Many
      of the children classified with ASD by the other measures were not classified
      with autism by the ADI-R because they did not display enough repetitive behaviors
      and stereotyped interests. These results indicate that young children with ASD
      may not display repetitive behaviors and stereotyped interests, and for toddlers,
      the ADI-R would have a higher sensitivity if revised to include a diagnosis of
      PDD-NOS, for which the requirement of repetitive behaviors is less stringent.

PMID- 16897399
TI  - Sex and discipline differences in empathising, systemising and autistic
      symptomatology: evidence from a student population.
AB  - Baron-Cohen's [(2002) Trends in Cognitive Sciences, 6, 248-255] 'extreme male
      brain' theory of autism is investigated by examining the relationships between
      theory of mind, central coherence, empathising, systemising and autistic-like
      symptomatology in typical undergraduates. There were sex differences in the
      expected directions on all tasks. Differences according to discipline were found
      only in central coherence. There was no evidence of an association between
      empathising and systemising. In the second study, performance on the Mechanical
      Reasoning task was compared with Systemising quotient and the Social Skills
      Inventory was compared with the Empathising Quotient. Moderate, but not high
      correlations were found. Findings are broadly consistent with the distinction
      between empathising and systemising but cast some doubt on the tasks used to
      measure these abilities.

PMID- 16897400
TI  - ERP evidence of atypical face processing in young children with autism.
AB  - Autism involves a basic impairment in social cognition. This study investigated
      early stage face processing in young children with autism by examining the face
      sensitive early negative event-related brain potential component in 3-4 year old
      children with autism spectrum disorder (ASD), typical development, and
      developmental delay. Results indicated that children with ASD showed a slower
      electrical brain response to faces and a larger amplitude response to objects
      compared to children with typical development and developmental delay. These
      findings indicate that children with ASD have a disordered pattern of brain
      responses to faces and objects at an early age.

PMID- 16897401
TI  - Psychopathology in children and adolescents with autism compared to young people
      with intellectual disability.
AB  - Autism is a neurodevelopmental disorder with a specific pattern of behavioural,
      communication and social problems. Additional mental health problems are often
      poorly understood and undetected. This study investigates the level and pattern
      of emotional and behavioural problems in young people with autism compared with
      children with intellectual disability (ID). Subjects were 381 young people with
      autism and a representative group of 581 Australian young people with ID aged 4
      18 years. Parents/carers provided details of the emotional and behavioural
      problems of their child using the Developmental Behaviour Checklist (DBC-P).
      Young people with autism were found to suffer from significantly higher levels of
      psychopathology than young people with ID. The implications of this finding are
      discussed.

PMID- 16897402
TI  - Lexical knowledge and lexical use in autism.
AB  - One aspect of autistic language that has been infrequently researched is
      vocabulary and the conceptual knowledge underpinning individual words or word
      types. In this descriptive study we investigate anomalous vocabulary use in a
      70,000-word corpus of conversational autistic language and examine evidence that
      concept formation, and hence vocabulary, is abnormal in autism. Particular
      attention is paid to the expression of artifact and temporal concepts which some
      believe may develop abnormally in autism. Little evidence is found of anomalous
      use of artifact terms, though errors with temporal (and also spatial) expressions
      are relatively common. We discuss why this may be and consider several potential
      explanations for why underlying lexical knowledge in autism may not necessarily
      be reflected in lexical use.

PMID- 16897404
TI  - Residual language deficits in optimal outcome children with a history of autism.
AB  - This study examined whether language deficits persist even in children with
      optimal outcomes. We examined a group of children with prior diagnoses on the
      autism spectrum who had IQs in the normal range, were in age-appropriate
      mainstream classes, and had improved to such an extent that they were considered
      to be functioning at the level of their typically developing peers. Fourteen such
      children between the ages of five and nine were matched on age and sex with
      typically developing children, and were given a battery of 10 language tests to
      investigate their language abilities. Results indicated that while these
      children's grammatical capabilities are mostly indistinguishable from their
      peers, they are still experiencing difficulties in pragmatic and semantic
      language.

PMID- 16897403
TI  - An open-label study of controlled-release melatonin in treatment of sleep
      disorders in children with autism.
AB  - Long-term effectiveness of controlled-release melatonin in 25 children, aged 2.6
      9.6 years with autism without other coexistent pathologies was evaluated openly.
      Sleep patterns were studied using Children's Sleep Habits Questionnaire (CSHQ)
      and sleep diaries at baseline, after 1-3-6 months melatonin treatment and 1 month
      after discontinuation. Sleep diary and CSHQ showed a more problematic sleep in
      autistic children compared with controls. During treatment sleep patterns of all
      children improved. After discontinuation 16 children returned to pre-treatment
      score, readministration of melatonin was again effective. Treatment gains were
      maintained at 12 and 24-month follow-ups. No adverse side effects were reported.
      In conclusion, controlled-release melatonin may provide an effective and well
      tolerated treatment for autistic children with chronic sleep disorders.

PMID- 16897405
TI  - Online mentoring: the promise and challenges of an emerging approach to youth
      development.
AB  - This paper reports on an electronic mentoring program, the Digital Heroes
      Campaign (DHC), in which 242 youth were matched with online mentors over a two
      year period. Survey, focus group, and interview data, in addition to analyses of
      the e-mails that pairs exchanged, were examined in order to assess the nature,
      types, and quality of the relationships that were formed. Despite youths'
      generally positive self-reports, deep connections between mentors and mentees
      appeared to be relatively rare. The findings suggest that online mentoring
      programs face significant challenges and that further research is needed to
      determine under what conditions online mentoring is likely to be most effective.

PMID- 16897406
TI  - At-risk high school students in the "Gaining Early Awareness and Readiness"
      Program (GEAR UP): academic and behavioral outcomes.
AB  - The purpose of this study was to assess the effects of a GEAR UP intervention
      with at-risk high school students at a large urban high school in Florida. The
      goals of the GEAR UP program were to improve academic performance, decrease
      behavior-related problems, and reduce truancy and absenteeism. The study design
      consisted of a three-group comparison of the 447 students in GEAR UP: the No
      Participation Group, the Low Participation Group, and the High Participation
      Group. Participation levels were calculated for each category of activity
      (academic, behavior-related, and social), and propensity scoring was used to
      match the groups on sociodemographic characteristics and other differentiating
      variables. Results indicated that race (i.e., African American) and sex (i.e.,
      female) are associated with high participation in program activities. Also,
      students who spent a substantial amount of time on academic activities improved
      their GPAs over a semester, and students who took advantage of behavior-related
      services and participated in social activities significantly reduced disciplinary
      referrals (p < .05). Suggestions for program refinement resulting from the study
      are discussed.

PMID- 16897407
TI  - Historical overview of primary prevention of psychopathology: address to the 3rd
      World Conference on the Promotion of Mental Health and Prevention of Mental and
      Behavioral Disorders September 15-17, 2004, Auckland, New Zealand.

PMID- 16897408
TI  - Editorial--What is primary prevention?

PMID- 16897409
TI  - Perceptions of tobacco use in early adolescents.
AB  - In an effort to strengthen tobacco use prevention programs, this study explores
      early (9- to 13-year-old) adolescent motivations for and perceptions of use. Data
      were collected, via electronic keypads, from students visiting 12 health
      education centers in the U.S. (N=1433). Multivariate logistic regression showed
      that perceptions of frequent peer tobacco use and popularity of adolescent
      smoking, in addition to absence of family discussion of tobacco use, were
      associated with greater likelihood for smoking and of reporting past smoking.
      Even though most participants thought adolescents who smoke are very unpopular,
      more than 60% said the primary reason for adolescent smoking was that smokers
      believe it will make them popular. Participants thought the best way to prevent
      use was to give kids "other fun things to do instead." Recommendations are given
      for customizing curricula or programs.

PMID- 16897410
TI  - Remission from pathological gambling among Hispanics and Native Americans.
AB  - This community survey studied remission from pathological gambling (PG) among
      American Indian (AI) and Hispanic American (HA) veterans. Remission was defined
      as having a lifetime diagnosis of PG, but no gambling symptoms in the last year.
      Sample consisted of 1624 AI and Hispanic veterans. Instruments included
      demographic data, the computer-based algorithmic Quick Diagnostic Interview
      Schedule Symptom, and three symptom checklists, one each for substance related
      problems (MAST/AD), anxiety and depressive symptoms (BSI-57), and combat-related
      post-trauma symptoms (PCL/M). Remission was associated with absence of a current
      Axis 1 diagnosis, especially absence of a current post-traumatic stress disorder.

PMID- 16897412
TI  - An examination of the African American experience of everyday discrimination and
      symptoms of psychological distress.
AB  - Current theoretical models suggest that the most potent and impacting
      discrimination experienced by African Americans in the post Jim Crow era are
      subtle and unconscious forms of discrimination that are experienced on a daily
      basis. This study investigates the relationship between perceived everyday
      discrimination and anxiety and depressive symptoms. Further, we examine gender as
      a moderator of this relationship. Data come from the 1995 Detroit Area Study data
      with 570 African American respondents. Results indicate that perceived
      discrimination is directly related to both symptoms of depression and anxiety.
      Gender moderates the relationship between discrimination and anxiety symptoms,
      but not discrimination and depressive symptoms. Overall, different patterns of
      relationships were apparent for men and women.

PMID- 16897411
TI  - Ethnic variation of self-reported psychopathology among incarcerated youth.
AB  - Research on ethnic minority populations has shown them to be undertreated,
      underdiagnosed and perceived as more psychopathological in comparison to the
      Caucasian population. This study aimed to assess ethnic variation of self
      perceived psychopathology in a population of incarcerated youths. The Youth Self
      Report (YSR) was completed by 5964 incarcerated adolescents (95% male; mean age =
      16.5) in the California Youth Authority (CYA) system. Overall, ethnic minorities
      (African-Americans and Hispanics) self-report lower levels of psychiatric
      problems than Caucasians. These differences were more pronounced in males than
      females. Further research is needed to better ascertain the reasons for these
      differences.

PMID- 16897413
TI  - Treating homeless clients with severe mental illness and substance use disorders:
      costs and outcomes.
AB  - This study compared the costs and outcomes associated with three treatment
      programs that served 149 individuals with dual disorders (i.e., individuals with
      co-occurring severe mental illness and substance use disorders) who were homeless
      at baseline. The three treatment programs were: Integrated Assertive Community
      Treatment (IACT), Assertive Community Treatment only (ACTO), and standard care
      (Control). Participants were randomly assigned to treatment and followed for a
      period of 24 months. Clients in the IACT and ACTO programs were more satisfied
      with their treatment program and reported more days in stable housing than
      clients in the Control condition. There were no significant differences between
      treatment groups on psychiatric symptoms and substance use. The average total
      costs associated with the IACT and Control conditions were significantly less
      than the average total costs for the ACTO condition.

PMID- 16897414
TI  - Telephone monitoring and support for veterans with chronic posttraumatic stress
      disorder: a pilot study.
AB  - Dropout from outpatient mental health treatment may contribute to high rates of
      relapse and rehospitalization among veterans with chronic posttraumatic stress
      disorder (PTSD). In a quasi-experimental cohort study, 87 male and 17 female
      veterans discharging from residential PTSD treatment received either standard
      referral to outpatient care (N = 77) or standard referrals supplemented by
      biweekly telephone calls (N = 27). Telephone monitoring and support was feasible
      and acceptable to 85% of clients. Compared to prior patient cohorts, clients
      receiving telephone support were twice as likely (88% vs. 43%) to complete an
      outpatient visit within 1 month of discharge and reported higher satisfaction
      with care.

PMID- 16897415
TI  - Health care access and utilization among women who have sex with women: sexual
      behavior and identity.
AB  - Past research has shown that women who either have sex with women or who identify
      as lesbian access less preventive health care than other women. However, previous
      studies have generally relied on convenience samples and have not examined the
      multiple associations of sexual identity, behavior and health care
      access/utilization. Unlike other studies, we used a multi-lingual population
      based survey in New York City to examine the use of Pap tests and mammograms, as
      well as health care coverage and the use of primary care providers, among women
      who have sex with women and by sexual identity status. We found that women who
      had sex with women (WSW) were less likely to have had a Pap test in the past 3
      years (66 vs. 80%, p<0.0001) or a mammogram in the past 2 years (53 vs. 73%,
      p=0.0009) than other women. After adjusting for health insurance coverage and
      other factors, WSW were ten times [adjusted odds ratio (AOR), 9.8, 95% confidence
      interval (CI), 4.2, 22.9] and four times (AOR, 4.0, 95% CI 1.3, 12.0) more likely
      than non-WSW to not have received a timely Pap test or mammogram, respectively.
      Women whose behavior and identity were concordant were more likely to access Pap
      tests and mammograms than those whose behavior and identity were discordant. For
      example, WSW who identified as lesbians were more likely to have received timely
      Pap tests (97 vs. 48%, p<0.0001) and mammograms (86 vs. 42%, p=0.0007) than those
      who identified as heterosexual. Given the current screening recommendations for
      Pap tests and mammograms, provider counseling and public health messages should
      be inclusive of women who have sex with women, including those who have sex with
      women but identify as heterosexual.

PMID- 16897416
TI  - Implementing a routine, voluntary HIV testing program in a Massachusetts county
      prison.
AB  - Although U.S. prison inmates have higher rates of HIV infection than the general
      population, most inmates are not routinely tested for HIV infection at prison
      entry. The study objective was to implement a routine, voluntary HIV testing
      program in a Massachusetts county prison. During admission, inmates were given
      group HIV pre-test counseling and were subsequently offered private HIV testing.
      This intervention was compared to a control period during which HIV testing was
      provided only upon inmate or physician request. Between November 2004 and April
      2005, 1,004 inmates met inclusion criteria and were offered routine, voluntary
      HIV testing. Of these, 734 (73.1%) accepted, 2 (0.3%) were HIV-infected, and 457
      (45.5%) had been tested for HIV in the previous year. The testing rate of 73.1%
      was significantly increased from the rate of 18.0% (318 of 1,723) during the
      control period (p<0.001). Among the inmates tested for HIV in the prior year,
      78.2% had received their last HIV test in the prison setting. Careful attention
      should be paid to prevent redundancy of testing efforts in the prison population.
      Implementing a routine HIV testing program among prison inmates greatly increased
      testing rates compared to on-request testing.

PMID- 16897417
TI  - Access to revascularization among patients with acute myocardial infarction in
      New York City--impact of hospital resources.
AB  - Timely revascularization can improve survival in patients with acute myocardial
      infarction. Identification of factors associated with increased use of
      revascularization in appropriate patients could improve outcomes. Using New York
      City hospital discharge records for 1988-1992 and 1998-2002, we determined
      revascularization rates for patients hospitalized with MI by neighborhood. Odds
      ratios for revascularization were estimated using a spatial model adjusting for
      neighborhood sociodemographic characteristics, while accounting for similarities
      in the rate of revascularization among geographically adjacent neighborhoods.
      Only 16 out of 112 New York City hospitals performed coronary revascularization.
      They were located in 14 of 41 neighborhoods. In general, patients living in
      neighborhoods with higher percentages of patients admitted to hospitals capable
      of revascularization service were more likely to be revascularized than those in
      neighborhoods with low percentages of patients admitted to hospitals with
      revascularization resources. This was true regardless of neighborhood
      availability of revascularization, after accounting for neighborhood
      socioeconomic characteristics and patients' clinical status. Revascularization
      rates in New York City increased from 1988-1992 to 1998-2002 in every
      neighborhood and as a whole from 103 to 326 per 1,000 hospitalized AMI patients.
      This increase was not explained by the addition of new revascularization
      services. Thus, in New York City, where only certain hospitals can perform
      revascularization, efficient delivery of patients to hospitals with these
      resources appears to increase the likelihood of revascularization performance
      among AMI patients without increasing the number of new hospitals capable of
      revascularization.

PMID- 16897419
TI  - Unrestrained acoustic plethysmograph for measuring tidal volume in mice.
AB  - The traditional method for measurement of tidal volume in unrestrained mice
      relies on pressure changes induced by a freely respiring animal in a whole body
      plethysmograph. These changes have been assumed to be the result of thermo
      hygrometric differences between respired air and gas within the chamber. It is
      known, however, that gas compression in the lung can also contribute
      significantly to changes in plethysmograph pressure. This study describes an
      acoustic plethysmograph for mice that is capable of measuring the tidal volume
      time series without the errors associated with the traditional method. The
      plethysmograph was designed as a resonating cavity at a fixed frequency. It had a
      sharp resonant peak and was tuned so that changes in body volume produced nearly
      linear changes in sound amplitude. The plethysmograph was tested with a water
      filled balloon connected to a syringe pump. The volume of the balloon was varied
      as a triangle wave with an amplitude of 250 microL. The RMS error between
      measured and delivered volume was 4.43 microL. A volume step test, performed to
      assess the response time of the system, showed that the plethysmograph responded
      in less than one millisecond.

PMID- 16897421
TI  - Stereolithography of three-dimensional bioactive poly(ethylene glycol) constructs
      with encapsulated cells.
AB  - Stereolithography (SL) was used to fabricate complex 3-D poly(ethylene glycol)
      (PEG) hydrogels. Photopolymerization experiments were performed to characterize
      the solutions for use in SL, where the crosslinked depth (or hydrogel thickness)
      was measured at different laser energies and photoinitiator (PI) concentrations
      for two concentrations of PEG-dimethacrylate in solution (20% and 30% (w/v)).
      Hydrogel thickness was a strong function of PEG concentration, PI type and
      concentration, and energy dosage, and these results were utilized to successfully
      fabricate complex hydrogel structures using SL, including structures with
      internal channels of various orientations and multi-material structures.
      Additionally, human dermal fibroblasts were encapsulated in bioactive PEG
      photocrosslinked in SL. Cell viability was at least 87% at 2 and 24 h following
      fabrication. The results presented here indicate that the use of SL and
      photocrosslinkable biomaterials, such as photocrosslinkable PEG, appears feasible
      for fabricating complex bioactive scaffolds with living cells for a variety of
      important tissue engineering applications.

PMID- 16897420
TI  - A direct compression stimulator for articular cartilage and meniscal explants.
AB  - This paper describes the development and use of a direct compression stimulator
      for culturing explants from the meniscus of the knee and articular cartilage.
      Following design and fabrication of the instrument along with its data
      acquisition system, the function of the machine was verified by both mechanical
      means and tissue effect. The loading chamber can hold up to 45 5 mm diameter
      samples. While designed to stimulate samples up to 4 mm thick, axial
      displacements as little as 0.127 microm are within the theoretical capacity of
      the stimulator. In gene expression studies, collagen II and aggrecan expression
      were examined in explants from articular cartilage as well as medial and lateral
      menisci subjected to dynamic stimulation and static compression. These results
      were then compared to free swelling samples. It was found that static compression
      to cut thickness down-regulated aggrecan and collagen II expression in articular
      cartilage explants compared to free swelling controls by 94% and 90%,
      respectively. The application of a dynamic, intermittent, 2% oscillation around
      the cut thickness returned expression levels to those of free swelling controls
      at 4 h but not at 76 h. In medial meniscus samples, dynamic compression up
      regulated aggrecan expression by 108%, but not collagen II expression, at 4 and
      76 h compared to static controls. No difference in gene expression was observed
      for lateral meniscal explants. Thus, effects of direct compression seen in
      articular cartilage may not necessarily translate to the knee meniscus. The
      design of this stimulator will allow a variety of tissues and loading regimens to
      be examined. It is hoped that regimens can be found that not only return samples
      to the production levels of free swelling controls, but also surpass them in
      terms of gene expression, protein synthesis, and functional properties.

PMID- 16897422
TI  - The effect of methanol on lipid bilayers: an atomistic investigation.
AB  - The interactions of methanol with lipid bilayers were studied by means of
      molecular dynamics (MD) simulations. Our MD simulations focus on the effect of
      approximately 11.3 mol% methanol on two fully hydrated
      dipalmitoylphosphatidylcholine (DPPC) and palmitoyloleoylphosphatidylcholine
      (POPC) lipid bilayers both in the fluid phase and under equilibrium conditions at
      323 and 298 K, respectively. The effects of methanol on bilayers structural
      characteristics were investigated. In both systems the simulations show that the
      presence of relatively high concentration of methanol leads to a significant
      increase in the area per lipid. The increase in the area per lipid is accompanied
      by a corresponding decrease of the bilayer thickness such that the volume
      occupied per lipid does not change significantly in the presence of methanol.
      Other properties such as ordering of phospholipid tails and lateral diffusion of
      the lipids are also affected significantly by the presence of methanol.
      Consistent with other previously reported MD simulation studies of bilayers in
      the presence of methanol (albeit at a significantly smaller concentration of 1
      mol%) our study shows very few hydrogen bonding formation between lipids and
      methanol.

PMID- 16897423
TI  - Three-dimensional finite element models of the human pubic symphysis with
      viscohyperelastic soft tissues.
AB  - Three-dimensional finite element (FE) models of human pubic symphyses were
      constructed from computed tomography image data of one male and one female
      cadaver pelvis. The pubic bones, interpubic fibrocartilaginous disc and four
      pubic ligaments were segmented semi-automatically and meshed with hexahedral
      elements using automatic mesh generation schemes. A two-term viscoelastic Prony
      series, determined by curve fitting results of compressive creep experiments, was
      used to model the rate-dependent effects of the interpubic disc and the pubic
      ligaments. Three-parameter Mooney-Rivlin material coefficients were calculated
      for the discs using a heuristic FE approach based on average experimental joint
      compression data. Similarly, a transversely isotropic hyperelastic material model
      was applied to the ligaments to capture average tensile responses. Linear elastic
      isotropic properties were assigned to bone. The applicability of the resulting
      models was tested in bending simulations in four directions and in tensile tests
      of varying load rates. The model-predicted results correlated reasonably with the
      joint bending stiffnesses and rate-dependent tensile responses measured in
      experiments, supporting the validity of the estimated material coefficients and
      overall modeling approach. This study represents an important and necessary step
      in the eventual development of biofidelic pelvis models to investigate symphysis
      response under high-energy impact conditions, such as motor vehicle collisions.

PMID- 16897424
TI  - The making of an interdisciplinary partnership: the case of the Chicago Food
      System Collaborative.
AB  - Interdisciplinary partnerships foster innovation to address pressing social
      problems. This paper describes an interdisciplinary partnership called the
      Chicago Food System Collaborative (CFSC) composed of a team of partners from four
      academic institutions and three community-based organizations representing a
      total of eight disciplines that included: community development and community
      organizing, community psychology, geography, nursing, nutrition, public health,
      sociology, and urban planning and policy. Partners came together to address the
      issue of access to healthy foods and nutrition in a working class African
      American neighborhood. We analyze and discuss the core principles that guided the
      partnership and its impact across three dimensions: understanding through
      interdisciplinary action research, building capacity, and facilitating
      innovations in practices and policies. Despite the challenges of
      interdisciplinary partnerships, the potential benefits and impact of such efforts
      reflect their value as a comprehensive approach to addressing complex social
      problems.

PMID- 16897425
TI  - Help-seeking behaviors of Chinese patients with schizophrenia admitted to a
      psychiatric hospital.
AB  - PURPOSE: To investigate the help-seeking behaviors and related factors of Chinese
      psychiatric inpatients with schizophrenia. METHOD: Two hundred and two patients
      with schizophrenia (ICD-10) were enrolled in this study. A locally-developed,
      semi-structured questionnaire was used to collect data, including data on illness
      and help-seeking histories from patients, informants, and medical records.
      RESULTS: Among 202 inpatients, 120 patients (59.4%) had sought help from at least
      one type of non-psychiatric facility (NPF), and 82 patients (40.6%) went to a
      psychiatric hospital directly. Among the NPFs they contacted, 66 patients (32.7%)
      tried traditional Chinese medicine (TCM) from licensed practitioners (including
      acupuncturists), 64 (31.7%) chose general hospitals (including 9 who went to
      emergency departments), and 52 (25.7%) sought help from qigong (breathing
      exercise) masters or other folk healing methods. The reasons for seeking
      treatment from NPFs varied; the most common ones included feeling shameful or
      stigmatized about going to psychiatric hospitals, inaccessibility to or
      unavailability of psychiatric hospitals, and fear of being incarcerated or
      receiving electric shock treatment. CONCLUSION: A substantial proportion of
      psychiatric inpatients in China seek help from non-psychiatric facilities and/or
      folk healing methods. Feeling shameful or stigmatized, inaccessibility to and/or
      unavailability of psychiatric services are among the most common barriers to
      seeking psychiatric treatment. Patients who sought psychiatric help directly are
      likely to be female, with a chronic onset of illness, a mixed syndrome of
      positive and negative symptoms, or a better economic status.

PMID- 16897426
TI  - A deletion in CHEK2 of 5,395 bp predisposes to breast cancer in Poland.
AB  - To investigate the contribution of a founder deletion in the CHEK2 gene to the
      burden of breast cancer in Poland we studied 4,454 women with breast cancer and
      5,496 population controls. Cases and controls were genotyped for the presence of
      a 5,395 bp founder deletion that removes exons 9 and 10 of the CHEK2 gene. This
      deletion has recently been described in a Czech and Slovak population. The cases
      and controls had previously been tested for two protein-truncating (IVS2 + 1G > A
      and 1100delC) and one missense CHEK2 mutation (I157T) which are characteristic
      for the population. The exons 9 and 10 deletion was present in 0.4% of the
      controls, in 1.0% (19 of 1,978) of unselected breast cancer cases (OR=2.2; 95%
      CI: 1.2-4.0; p = 0.01) and in 0.9% (28 of 3,228) of the early-onset cases
      (OR=2.0; 95% CI: 1.3-1.8; p = 0.02). One of the three truncating CHEK2 mutations
      (del5395; 1100delC or IVS2 + 1G > A) was seen in 101 of 4,454 (2.3%) cases and in
      58 of 5,496 controls (1.1%) (OR=2.2; 95% CI: 1.6-3.0 p < 0.0001). A 5,395 bp
      founder deletion contributes to the burden of breast cancer in Poland. The
      deletion was present in 0.9% of the women with breast cancer diagnosed under the
      age of 51 and in 0.9% of women with breast cancer over the age of 50. This is one
      of the most common protein-truncating CHEK2 variants in Poland. Overall, 2% of
      all breast cancers in Poland can be attributed to one of three protein-truncating
      mutations in CHEK2.

PMID- 16897427
TI  - Monitoring primary breast cancer throughout chemotherapy using FDG-PET.
AB  - We have compared 2-deoxy-2-[(18)F]-fluoro-D-glucose positron emission tomography
      (FDG-PET) images of large or locally advanced breast cancers (LABC) acquired
      during Anthracycline-based chemotherapy. The purpose was to determine whether
      there is an optimal method for defining tumour volume and an optimal imaging time
      for predicting pathologic chemotherapy response. METHOD: PET data were acquired
      before the first and second cycles, at the midpoint and at the endpoint of
      neoadjuvant chemotherapy. FDG uptake was quantified using the mean and maximum
      standardized uptake values (SUV) and the coefficient of variation within a region
      of interest. Receiver-operator characteristic (ROC) analysis was used to
      determine the discrimination between tumours demonstrating a high pathological
      response (i.e. those with greater than 90% reduction in viable tumour cells) and
      low pathological response. RESULTS: Only tumours with an initial tumour to
      background ratio (TBR) of greater than five showed a difference between response
      categories. In terms of response discrimination, there was no statistically
      significant advantage of any of the methods used for image quantification or any
      of the time points. The best discrimination was measured for mean SUV at the
      midpoint of therapy, which identified 77% of low responding tumours whilst
      correctly identifying 100% of high responding tumours and had an ROC area of
      0.93. CONCLUSION: FDG-PET is efficacious for predicting the pathologic response
      of most primary breast tumours throughout the duration of a neoadjuvant
      chemotherapy regimen. However, this technique is ineffective for tumours with low
      image contrast on pre-therapy PET scans.

PMID- 16897428
TI  - Expression of protein elongation factor eEF1A2 predicts favorable outcome in
      breast cancer.
AB  - Breast cancer is the most common malignancy among North American women. The
      identification of factors that predict outcome is key to individualized disease
      management and to our understanding of breast oncogenesis. We have analyzed mRNA
      expression of protein elongation factor eEF1A2 in two independent breast tumor
      populations of size n = 345 and n = 88, respectively. We find that eEF1A2 mRNA is
      expressed at a low level in normal breast epithelium but is detectably expressed
      in approximately 50-60% of primary human breast tumors. We have derived an eEF1A2
      specific antibody and measured eEF1A2 protein expression in a sample of 438
      primary breast tumors annotated with 20-year survival data. We find that high
      levels of eEF1A2 protein are detected in 60% of primary breast tumors independent
      of HER-2 protein expression, tumor size, lymph node status, and estrogen receptor
      (ER) expression. Importantly, we find that high eEF1A2 is a significant predictor
      of outcome. Women whose tumor has high eEF1A2 protein expression have an
      increased probability of 20-year survival compared to those women whose tumor
      does not express substantial eEF1A2. In addition, eEF1A2 protein expression
      predicts increased survival probability in those breast cancer patients whose
      tumor is HER-2 negative or who have lymph node involvement.

PMID- 16897429
TI  - Prostate-derived Ets transcription factor (PDEF) downregulates survivin
      expression and inhibits breast cancer cell growth in vitro and xenograft tumor
      formation in vivo.
AB  - Previous studies using immunohistochemistry suggest that loss of the expression
      of the prostate-derived Ets transcription factor (PDEF) is a strong indicator for
      cancer cell malignancy. However, the underlying mechanism for this has not been
      well elucidated. We determined the role of PDEF in breast cancer cell growth and
      tumor formation using a series of experiments including Western blotting,
      promoter-luciferase reporter assay, RNA interference technology and a mouse
      xenograft model. We also determined the relationship between PDEF expression in
      human breast tumor specimen and cancer patient survivability. These studies
      revealed that PDEF expression is inversely associated with survivin expression
      and breast cancer cell xenograft tumor formation. PDEF-specific shRNA-mediated
      silencing of PDEF expression resulted in the upregulation of survivin expression
      in MCF-7 cells, which was associated with increased cell growth and resistance to
      drug-induced DNA fragmentation (apoptosis). In contrast, survivin-specific siRNA
      mediated silencing of survivin expression decreased MCF-7 cell growth. Ectopic
      expression of PDEF inhibited both survivin promoter activity and endogenous
      survivin expression. Importantly, shRNA-mediated silencing of PDEF expression in
      MCF-7 breast cancer cells enhanced survivin expression and xenograft tumor
      formation in vivo. Furthermore, loss of PDEF expression in breast cancer tissues
      tends to be associated with unfavorable prognosis. These studies provide new
      information for the role of PDEF and survivin in breast cancer cell growth and
      tumor formation.

PMID- 16897430
TI  - Coordinated steroid hormone-dependent and independent expression of multiple
      kallikreins in breast cancer cell lines.
AB  - The regulation of gene expression by steroid hormones plays an important role in
      the normal development and function of many organs, as well in the pathogenesis
      of endocrine-related cancers. Previous experiments have shown that many
      kallikrein genes are under steroid hormone regulation in breast cancer cell
      lines. We here examine the coordinated expression of multiple kallikrein genes in
      several breast cancer cell lines after steroid hormone stimulation. Breast cancer
      cell lines were treated with various steroid hormones and kallikrein (KLK/hK)
      expression of hK3 (prostate-specific antigen, PSA), hK5, hK6, hK7, hK8, hK10,
      hK11, hK13, and hK14 was analyzed at the RNA level via RT-PCR and at the protein
      level by immunofluorometric ELISA assays. We identified several distinct hK
      hormone-dependent and hormone-independent expression patterns. Hormone-specific
      modulation of expression was seen for several kallikreins in BT-474, MCF-7, and T
      47D cell lines. hK6 was specifically up-regulated upon estradiol treatment in all
      three cell lines whereas PSA expression was induced by dihydrotestosterone (DHT)
      and norgestrel stimulation in BT-474 and T-47D. hK10, hK11, hK13, and hK14 were
      specifically up-regulated by DHT in T-47D and by estradiol in BT-474 cells.
      Bioinformatic analysis of upstream proximal promoter sequences for these hKs did
      not identify any recognizable hormone-response elements (HREs), suggesting that
      the coordinated activation of these four hKs represents a unique expression
      "cassette", utilizing a common hormone-dependent mechanism. We conclude that
      groups of human hKs are coordinately expressed in a steroid hormone-dependent
      manner. Our data supports clinical observations linking expression of multiple
      hKs with breast cancer prognosis.

PMID- 16897431
TI  - The combination of letrozole and trastuzumab as first or second-line biological
      therapy produces durable responses in a subset of HER2 positive and ER positive
      advanced breast cancers.
AB  - BACKGROUND: Estrogen receptor (ER) and/or progesterone receptor expression occurs
      in approximately 50% HER2 positive (HER2+) breast cancers and cross-talk between
      the estrogen and HER2 pathways promotes endocrine therapy resistance. The
      efficacy of the aromatase inhibitor letrozole in combination with trastuzumab was
      therefore tested in a Phase 2 study. METHODS: Patients with ER+ and/or PgR+ and
      HER2+ (IHC 2+ or 3+ or FISH+) advanced breast cancer were treated with
      trastuzumab plus letrozole until disease progression or unacceptable toxicity.
      RESULTS: Thirty-three patients were enrolled, of which thirty one were considered
      evaluable. The majority of patients (82%) had received tamoxifen and 82% had HER2
      FISH+ and/or IHC 3+ tumors. Eight patients responded (1 CR and 7 PR) for an
      overall response rate (ORR) of 26% and a clinical benefit rate (CBR) of 52%. The
      median time to progression (TTP) was 5.8 months and the median duration of
      response (DOR) was 20.6+ months. Excluding IHC 2+, FISH- tumors, the OR was 24%,
      CBR 44%, TTP 5.5 months and DOR 17+ months. The combination was well tolerated
      with only two toxicity events requiring termination of study medication.
      CONCLUSIONS: Combined trastuzumab and letrozole treatment for patients with HER2+
      and ER+ advanced breast cancer produced durable responses consistently lasting at
      least 1 year in one quarter of the patients. While these data are promising for a
      subgroup, for half the patients, trastuzumab plus letrozole was inactive. This
      finding demonstrates ER+ HER2+ advanced disease is heterogeneous and additional
      agents will be required for optimal management based on targeted therapeutics
      alone.

PMID- 16897432
TI  - Overexpression of the wip1 gene abrogates the p38 MAPK/p53/Wip1 pathway and
      silences p16 expression in human breast cancers.
AB  - Wild-type p53-induced phosphatase (Wip1 or PPM1D) is a serine/threonine protein
      phosphatase expressed under various stress conditions, which selectively
      inactivates p38 MAPK. The finding that this gene is amplified in association with
      frequent gain of 17q21-24 in breast cancers supports its role as a driver
      oncogene. However, the pathogenetic mechanism of the wip1 gene expression in
      breast carcinogenesis remains to be elucidated. In this study, we examine Wip1
      mRNA and protein expression in 20 breast cancer tissues and six cell lines. We
      additionally investigate the relationship among Wip1, active p38 MAPK, p53, and
      p16 proteins. In our experiments, Wip1 mRNA was significantly upregulated in 7 of
      20 (35%) invasive breast cancer samples. Overexpression of Wip1 was inversely
      correlated with that of active (phosphor-) p38 MAPK (P = 0.007). Furthermore,
      Wip1-overexpressing tumors exhibited no or low levels of p16, which normally
      accumulates upon p38 MAPK activation (P = 0.057). Loss of p16 expression was not
      associated with hypermethylation of its promoter or loss of heterozygosity on
      9p21. Among the 135 primary breast carcinomas further examined, a significant
      association was found between the Wip1 overexpression and negative staining for
      p53 (P value = 0.057), indicating that the tumors are wild-type for p53. This is
      first report showing that Wip1 overexpression abrogates the homeostatic balance
      maintained through the p38-p53-Wip1 pathway, and contributes to malignant
      progression by inactivating wild-type p53 and p38 MAPK as well as decreasing p16
      protein levels in human breast tissues.

PMID- 16897434
TI  - Aromatase inhibitors reverse tamoxifen induced endometrial ultrasonographic
      changes in postmenopausal breast cancer patients.
AB  - OBJECTIVE: Aromatase inhibitors may decrease endometrial thickness in breast
      cancer patients previously having short-term tamoxifen treatment. There is a
      necessity to find out if aromatase inhibitors can also decrease endometrial
      thickness in patients previously treated with long-term tamoxifen treatment.
      METHODS: Prospective comparison of the last ultrasonographic endometrial
      thickness measurement taken before discontinuation of long-term tamoxifen
      treatment in 36 postmenopausal breast cancer patients, with further measurements,
      performed following aromatase inhibitors administration. RESULTS: There was a
      significant decrement of endometrial thickness, following 36.2 +/- 16.8 months of
      tamoxifen treatment, from a mean value of 9.1 +/- 5.8 mm, measured at the last
      ultrasonographic measurement performed before discontinuation of tamoxifen
      treatment, down to a mean value of 6.0 +/- 5.0 mm, measured following 5.8 +/- 5.8
      months of aromatase inhibitors therapy (P = 0.001). A second ultrasonographic
      measurement performed in 8 patients following of additional 7.5 +/- 4.0 months of
      aromatase inhibitors treatment revealed further decrement of mean endometrial
      thickness to 4.8 +/- 2.1 mm (P = 0.002 compared to baseline). In 28 patients
      (77.8%), endometrial thickness was reduced following the administration of
      aromatase inhibitors, in four patients (11.1%) there was no change in endometrial
      thickness and four (11.1%) patients demonstrated an increase of endometrial
      thickness. CONCLUSIONS: Aromatase inhibitors may reverse endometrial thickening
      induced by long-term tamoxifen treatment in postmenopausal breast cancer
      patients.

PMID- 16897433
TI  - Cost-utility of adjuvant hormone therapies for breast cancer in post-menopausal
      women: sequential tamoxifen-exemestane and upfront anastrozole.
AB  - BACKGROUND: Adjuvant Anastrozole (ANA) for 5 years and Tamoxifen followed by
      Exemestane (TAM-EXE) for 2.5 years each have become acceptable alternatives to 5
      years of Tamoxifen (TAM) for post-menopausal women with breast cancer. As these
      newer options are associated with higher drug costs as well as improved outcomes,
      an economic evaluation was undertaken to compare the cost-utility of ANA and TAM
      EXE relative to TAM alone and to each other in terms of cost per quality-adjusted
      life year (QALY) gained. METHODS: A Markov model was developed to calculate
      monthly costs and outcomes in a hypothetical cohort of post-menopausal women with
      early-stage breast cancer. Baseline rates of cancer recurrence and adverse
      effects with TAM, and hazard ratios associated with ANA and EXE, were derived
      from the ATAC and IES trials. Patients received hormonal therapy for 5 years and
      benefit was modeled to persist 5 years beyond treatment. The analysis took a
      direct payer perspective with a 20-year time horizon. Costs and outcomes were
      discounted by 3%. Costs are in 2005 Canadian dollars. RESULTS: ANA and TAM-EXE
      were associated with increased costs and QALYs, though the cost-utility of both
      relative to TAM alone was strongly favourable (<$50,000/QALY). Based on an
      indirect comparison of ANA and TAM-EXE, using TAM alone as a common comparator,
      the cost-utility of ANA relative to TAM-EXE appears unfavourable. CONCLUSIONS:
      Both upfront and sequential AI options were cost-effective alternatives to TAM
      alone, but TAM-EXE appears to be the economically preferred AI option based on
      its more favourable cost-utility versus ANA.

PMID- 16897435
TI  - Albumin-bound paclitaxel, ABI-007 may show better efficacy than paclitaxel in
      basal-like breast cancers: association between caveolin-1 expression and ABI-007.

PMID- 16897436
TI  - Subclinical pregnancy losses among women undergoing in-vitro fertilization with
      ICSI.
AB  - BACKGROUND: The purpose of this study is to asses the frequency of subclinical
      pregnancy loss (SPL) among women undergoing controlled ovarian hyperstimulation
      (COH) and in-vitro fertilization with ICSI. METHODS: The study was
      retrospectively conducted in a private IVF center. SPL was defined by a temporary
      rise in serum beta hCG, along with the absence of signs of intra- and extra
      uterine pregnancy by transvaginal ultrasonography. Overall 5273 COH and ICSI
      cycles with embryo transfer (ET) were segregated according to serum E(2) levels
      percentiles (-24th, 25th, 74th, and 75th), women age and the type of spermatozoa
      for assisted fertilization (ejaculated and surgically retrieved). Those groups
      were assessed for SPL rates. RESULTS: Among the 3125 (59.25) conception cycles,
      305 (9.7%) were diagnosed as SPL. There was no difference in SPL rate among E(2)
      percentile groups. Women older than 35 years of age had significantly higher rate
      of SPL compared to younger women. There was also no difference in SPL rate among
      pregnancies in whom surgically retrieved spermatozoa used or ejaculated
      spermatozoa used for assisted fertilization. CONCLUSION: Our results demonstrated
      that SPL rate was not influenced by the levels of E(2) during COH or the origin
      of spermatozoa used for assisted fertilization. However, maternal age was found
      to be detrimental for SPL.

PMID- 16897437
TI  - Structural and functional analysis of the coupling subunit F in solution and
      topological arrangement of the stalk domains of the methanogenic A1AO ATP
      synthase.
AB  - The first low-resolution shape of subunit F of the A(1)A(O) ATP synthase from the
      archaeon Methanosarcina mazei Go1 in solution was determined by small angle X-ray
      scattering. Independent to the concentration used, the protein is monomeric and
      has an elongated shape, divided in a main globular part with a length of about
      4.5 nm, and a hook-like domain of about 3.0 nm in length. The subunit-subunit
      interaction of subunit F inside the A(1)A(O) ATP synthase in the presence of 1
      ethyl-3-(dimethylaminopropyl)-carbodiimide EDC was studied as a function of
      nucleotide binding, demonstrating movements of subunits F relative to the
      nucleotide-binding subunit B. Furthermore, in the intact A(1)A(O) complex,
      crosslinking of subunits D-E, A-H and A-B-D was obtained and the peptides,
      involved, were analyzed by MALDI-TOF mass spectrometry. Based on these data the
      surface of contact of B-F could be mapped in the high-resolution structure of
      subunit B of the A(1)A(O) ATP synthase.

PMID- 16897439
TI  - Effects of pulsed electric fields on DNA of human lymphocytes.
AB  - The effects of pulsed electric fields of low frequency (50 Hz) on DNA of human
      lymphocytes were investigated. The influence of additional external factors, such
      as hydrogen peroxide (H2O2) and gamma-irradiation, as well as the repair
      efficiency in these lymphocytes, was also evaluated. The comet assay, a very
      sensitive and rapid method for detecting DNA damage at the single cells level was
      the method used. A significant amount of damage was observed after exposure to
      the electric fields, compared to the controls. After 2 h incubation at 37 degrees
      C, a proportion of damage was repaired. H2O2 and gamma-irradiation increased the
      damage to lymphocytes exposed to pulsed electric fields according to the dose
      used, while the amount of the repair was proportional to the damage.

PMID- 16897438
TI  - Caenorhabditis elegans MAI-1 protein, which is similar to mitochondrial ATPase
      inhibitor (IF1), can inhibit yeast F0F1-ATPase but cannot be transported to yeast
      mitochondria.
AB  - In Caenorhabditis elegans, two proteins that are similar to mitochondrial ATPase
      inhibitor protein (IF(1)) have been found and named MAI-1 and MAI-2. In this
      study, we overexpressed and purified both the proteins and examined their
      properties. Circular dichroism spectra indicated that both the MAI-1 and MAI-2
      predominantly consisted of beta- and random structure, and in contrast to
      mammalian IF(1), alpha-helixes were barely detected. Both MAI-1 and MAI-2 could
      inhibit yeast F(0)F(1)-ATPase, but the inhibition by MAI-1 was pH-independent.
      MAI-2-GFP fusion protein was transported to yeast mitochondria, but MAI-1-GFP was
      not. These results indicate that the MAI-2 is (C. elegans) IF(1). MAI-1 seems to
      be a cytosolic protein and may regulate cytosolic ATPase(s).

PMID- 16897440
TI  - Glioblastoma cell death induced by asiatic acid.
AB  - Asiatic acid (AA), a triterpene, is known to be cytotoxic to several tumor cell
      lines. AA induces dose- and time-dependent cell death in U-87 MG human
      glioblastoma. This cell death occurs via both apoptosis and necrosis. The effect
      of AA may be cell type-specific as AA-induced cell death was mainly apoptotic in
      colon cancer RKO cells. AA-induced glioblastoma cell death is associated with
      decreased mitochondrial membrane potential, activation of caspase-9 and -3, and
      increased intracellular free Ca2+. Although treatment of glioblastoma cells with
      the caspase inhibitor zVAD-fmk completely abolished AA-induced caspase
      activation, it did not significantly block AA-induced cell death. AA-induced cell
      death was significantly prevented by an intracellular Ca2+ inhibitor, BAPTA/AM.
      Taken together, these results indicate that AA induces cell death by both
      apoptosis and necrosis, with Ca2+-mediated necrotic cell death predominating.

PMID- 16897441
TI  - Chloramphenicol induces in vitro growth arrest and apoptosis of human
      keratinocytes.
AB  - Chloramphenicol (CAP) is a broad-spectrum antibacterial drug that is widely used
      for topical application in ophthalmology and dermatology. In the present study we
      investigated the influence of CAP on human keratinocyte proliferation and
      apoptosis in vitro. CAP significantly inhibited proliferation and induced
      apoptosis of cultivated human keratinocytes, as revealed by incorporation of
      radioactive thymidine and flow cytometry analysis of intracellular esterase
      activity in fluorescein diacetate-stained cells, respectively. CAP-induced
      keratinocyte apoptosis was associated with activation of caspases and increased
      production of reactive oxygen species. The pro-apoptotic action of CAP was
      antagonized by the antioxidant agent N-acetylcysteine, the protein synthesis
      inhibitor cycloheximide, and PD98059, a selective inhibitor of extracellular
      signal-regulated kinase (ERK) activation. Taken together, these data indicate
      that CAP inhibits keratinocyte proliferation through induction of oxidative
      stress and ERK-mediated caspase-dependent apoptosis.

PMID- 16897442
TI  - Evolutionary pattern of the gtwin retrotransposon in the Drosophila melanogaster
      subgroup.
AB  - The gtwin retrotransposon was recently discovered in the Drosophila melanogaster
      genome and it is evolutionarily closer to gypsy endogenous retrovirus. This study
      has identified gtwin homologous sequences in the genome of D. simulans, D.
      sechellia, D. erecta and D. yakuba by performing homology searches against the
      public genome database of Drosophila species. The phylogenetic analyses of the
      gtwin env gene sequences of these species have shown some incongruities with the
      host species phylogeny, suggesting some horizontal transfer events for this
      retroelement. Moreover, we reported the existence of DNA sequences putatively
      encoding full-length Env proteins in the genomes of Drosophila species other than
      D. melanogaster. The results suggest that the gtwin element may be an infectious
      retrovirus able to invade the genome of new species, supporting the gtwin
      evolutionary picture shown in this work.

PMID- 16897443
TI  - Early replication banding in Leporinus species (Osteichthyes, Characiformes)
      bearing differentiated sex chromosomes (ZW).
AB  - There are few examples of differentiated sex chromosomes in fishes. In the genus
      Leporinus, seven species present a highly differentiated ZW system, derived from
      heterochromatinization process. Cytogenetic analyses carried out in three of
      these fish species, Leporinus obtusidens, L. elongatus and L. reinhardti, through
      RBG-banding, showed late replication bands, coincident with heterochromatic
      regions in both Z and W chromosomes. A similar interstitial early replication
      segment was observed in the complex heterochromatic region along the Wq arms in
      the three species, which might correspond to a pseudoautosomal segment (SD, sex
      determining locus). Asynchrony related to the replication pattern among different
      Z chromosomes was not observed. When the identification of nuclear organizer
      regions by silver nitrate was performed over chromosomal preparations previously
      exposed to 5-bromo-2'-deoxyuridine (BrdU), remarkable positive signals at
      interstitial and telomeric position were observed on the q arms of W chromosomes
      in the species L. elongatus and L. reinhardti. The absence of 18S ribosomal RNA
      gene loci in this region, formerly demonstrated by FISH, indicates that this
      argentophilic behavior is putatively due to heterochromatin decondensation caused
      by BrdU incorporation, favoring such Ag+ reaction. Early and late replication
      bands were also observed in the heterochromatic portions of Z and W chromosomes,
      indicating that euchromatic and heterochromatic regions are interspersed. The
      present data suggest a significant level of heterochromatic complexity in the sex
      chromosomes of each species. On the other hand, the replication pattern shared by
      them supports a monophyletic origin.

PMID- 16897444
TI  - Patterns of genetic diversity and differentiation in the tsetse fly Glossina
      morsitans morsitans Westwood populations in East and southern Africa.
AB  - Genetic diversity and differentiation within and among nine G. morsitans
      morsitans populations from East and southern Africa was assessed by examining
      variation at seven microsatellite loci and a mitochondrial locus, cytochrome
      oxidase (COI). Mean COI diversity within populations was 0.63+/-0.33 and 0.81
      taken over all populations. Diversities averaged over microsatellite loci were
      high (mean number of alleles/locus>or=7.4; mean HE>or=65%) in all populations.
      Diversities averaged across populations were greater in East Africa (mean number
      of alleles=22+/-2.6; mean he=0.773+/-0.033) than in southern Africa (mean number
      of alleles=18.7+/-4.0; mean he=0.713+/-0.072). Differentiation among all
      populations was highly significant (RST=0.25, FST=0.132). Nei's Gij statistics
      were 0.09 and 0.19 within regions for microsatellites and mitochondria,
      respectively; between regions, Gij was 0.14 for microsatellites and 0.23 for
      mitochondria. GST among populations was 0.23 for microsatellite loci and 0.40 for
      mitochondria. The F, G and R statistics indicate highly restricted gene flow
      among G. m. morsitans populations separated over geographic scales of 12-917 km.

PMID- 16897446
TI  - Diversity in isochore structure among cold-blooded vertebrates based on GC
      content of coding and non-coding sequences.
AB  - To review the general consideration about the different compositional structure
      of warm and cold-blooded vertebrates genomes, we used of the increasing number of
      genetic sequences, including coding (exons) and non-coding (introns) regions,
      that have been deposited on the databases throughout last years. The nucleotide
      distributions of the third codon positions (GC3) have been analyzed in 1510
      coding sequences (CDS) of fish, 1414 CDS of amphibians and 320 CDS of reptiles.
      Also, the relationship between GC content of 74, 56 and 25 CDS of fish,
      amphibians and reptiles, respectively and that of their corresponding introns
      (GCI) have been considerated. In accordance with recent data, sequence analysis
      showed the presence of very GC3-rich CDS in these poikilotherm vertebrates.
      However, very high diversity in compositional patterns among different orders of
      fish, amphibians and reptiles was found. Significant positive correlations
      between GC3 and GCI was also confirmed for the genes analyzed. Nevertheless,
      introns resulted to be poorer in GC than their corresponding CDS, this difference
      being larger than in human genome. Because the limited number of available
      sequences including exons and introns we must be cautious about the results
      derived from them. However, the indicious of higher GC richness of coding
      sequences than of their corresponding introns could aid to understand the
      discrepancy of sequence analysis with the ultracentrifugation studies in cold
      blooded vertebrates that did not predict the existence of GC-rich isochores.

PMID- 16897445
TI  - Physical mapping of 5S and 45S rDNA loci in pufferfishes (Tetraodontiformes).
AB  - Chromosomal features, location and variation of the major and minor rDNA genes
      cluster were studied in three pufferfish species: Sphoeroides greeleyi and
      Sphoeroides testudineus (Tetraodontidae) and Cyclichthys spinosus (Diodontidae).
      The location of the major rDNA was revealed with an 18S probe in two loci for all
      species. The minor rDNA loci (5S rDNA) was found in one chromosome pair in
      tetraodontid fishes and four sites located on two distinct chromosomal pairs in
      C. spinosus. A syntenical organization was not observed among the ribosomal
      genes. Signal homogeneity for GC/AT-DNA specific fluorochromes was observed in
      diodontid fish except in the NORs regions, which were CMA3-positive. Giemsa
      karyotypes of tetraodontid species presents 2n=46, having the same diploid value
      of other Sphoeroides species that have been investigated. On the other hand, the
      karyotype of C. spinosus, described for the first time, shows 2n=50 chromosomes
      (4m+18sm+12st+16a). The foreknowledge of the karyotypic structure of this group
      and also the physical mapping of certain genes could be very helpful for further
      DNA sequence analysis.

PMID- 16897447
TI  - A simple chromosomal marker can reliably distinguishes Poncirus from Citrus
      species.
AB  - Several chromosome types have been recognized in Citrus and related genera by
      chromomycin A(3 )(CMA) banding patterns and fluorescent in situ hybridization
      (FISH). They can be used to characterize cultivars and species or as markers in
      hybridization and backcrossing experiments. In the present work, characterization
      of six cultivars of P. trifoliata ("Barnes", "Fawcett", "Flying Dragon",
      "Pomeroy", "Rubidoux", "USDA") and one P. trifoliata x C. limonia hybrid was
      performed by sequential analyses of CMA banding and FISH using 5S and 45S rDNA as
      probes. All six cultivars showed a similar CMA(+) banding pattern with the
      karyotype formula 4B + 8D + 6F. The capital letters indicate chromosomal types:
      B, a chromosome with one telomeric and one proximal band; D, with only one
      telomeric band; F, without bands. In situ hybridization labeling was also similar
      among cultivars. Three chromosome pairs displayed a closely linked set of 5S and
      45S rDNA sites, two of them co-located with the proximal band of the B type
      chromosomes (B/5S-45S) and the third one co-located with the terminal band of a D
      pair (D/5S-45S). The B/5S-45S chromosome has never been found in any citrus
      accessions investigated so far. Therefore, this B chromosome can be used as a
      marker to recognize the intergeneric Poncirus x Citrus hybrids. The intergeneric
      hybrid analyzed here displayed the karyotype formula 4B + 8D + 6F, with two
      chromosome types B/5S-45S and two D/5S-45S. The karyotype formula and the
      presence of two B/5S-45S chromosomes clearly indicate that the plant investigated
      is a symmetric hybrid. It also demonstrates the suitability of karyotype analyses
      to differentiate zygotic embryos or somatic cell fusions involving trifoliate
      orange germplasm.

PMID- 16897449
TI  - Polytene chromosome maps in four species of tsetse flies Glossina austeni, G.
      pallidipes, G. morsitans morsitans and G. m. submorsitans (Diptera: Glossinidae):
      a comparative analysis.
AB  - Photographic polytene chromosome maps from pupal trichogen cells of four tsetse
      species, Glossina austeni, G. pallidipes, G. morsitans morsitans and G. m.
      submorsitans were constructed and compared. The homology of chromosomal elements
      between the species was achieved by comparing banding patterns. The telomeric and
      subtelomeric chromosome regions were found to be identical in all species. The
      pericentromeric regions were found to be similar in the X chromosome and the left
      arm of L1 chromosome (L1L) but different in L2 chromosome and the right arm of L1
      chromosome (L1R). The L2 chromosome differs by a pericentric inversion that is
      fixed in the three species, G. pallidipes, G. morsitans morsitans and G. m.
      submorsitans. Moreover, the two morsitans subspecies appeared to be
      homosequential and differ only by two paracentric inversions on XL and L2L arm.
      Although a degree of similarity was observed across the homologous chromosomes in
      the four species, the relative position of specific chromosome regions was
      different due to chromosome inversions established during their phylogeny.
      However, there are regions that show no apparent homology between the species, an
      observation that may be attributed to the considerable intra--chromosomal
      rearrangements that have occurred following the species divergence. The results
      of this comparative analysis support the current phylogenetic relationships of
      the genus Glossina.

PMID- 16897448
TI  - 5S rDNA variation and its phylogenetic inference in the genus Leporinus
      (Characiformes: Anostomidae).
AB  - 5S rDNA sequences have proven to be valuable as genetic markers to distinguish
      closely related species and also in the understanding of the dynamic of
      repetitive sequences in the genomes. In the aim to contribute to the knowledge of
      the evolutionary history of Leporinus (Anostomidae) and also to contribute to the
      understanding of the 5S rDNA sequences organization in the fish genome, analyses
      of 5S rDNA sequences were conducted in seven species of this genus. The 5S rRNA
      gene sequence was highly conserved among Leporinus species, whereas NTS exhibit
      high levels of variations related to insertions, deletions, microrepeats, and
      base substitutions. The phylogenetic analysis of the 5S rDNA sequences clustered
      the species into two clades that are in agreement with cytogenetic and
      morphological data.

PMID- 16897450
TI  - Studies of threespine stickleback developmental evolution: progress and promise.
AB  - A promising route for understanding the origin and diversification of organismal
      form is through studies at the intersection of evolution and development (evo
      devo). While much has been learned over the last two decades concerning
      macroevolutionary patterns of developmental change, a fundamental gap in the evo
      devo synthesis is the integration of mathematical population and quantitative
      genetics with studies of how genetic variation in natural populations affects
      developmental processes. This micro-evo-devo synthesis requires model organisms
      with which to ask empirical questions. Threespine stickleback fish (Gasterosteus
      aculeatus), long a model for studying behavior, ecology and evolution, is
      emerging as a prominent model micro-evo-devo system. Research on stickleback over
      the last decade has begun to address the genetic basis of morphological variation
      and sex determination, and much of this work has important implications for
      understanding the genetics of speciation. In this paper we review recent
      threespine stickleback micro-evo-devo results, and outline the resources that
      have been developed to make this synthesis possible. The prospects for
      stickleback research to speed the micro-(and macro-) evo-devo syntheses are
      great, and this workhorse model system is well situated to continue contributing
      to our understanding of the generation of diversity in organismal form for many
      more decades.

PMID- 16897451
TI  - Functional and evolutionary inference in gene networks: does topology matter?
AB  - The relationship between the topology of a biological network and its functional
      or evolutionary properties has attracted much recent interest. It has been
      suggested that most, if not all, biological networks are 'scale free.' That is,
      their connections follow power-law distributions, such that there are very few
      nodes with very many connections and vice versa. The number of target genes of
      known transcriptional regulators in the yeast, Saccharomyces cerevisiae, appears
      to follow such a distribution, as do other networks, such as the yeast network of
      protein-protein interactions. These findings have inspired attempts to draw
      biological inferences from general properties associated with scale-free network
      topology. One often cited general property is that, when compromised, highly
      connected nodes will tend to have a larger effect on network function than
      sparsely connected nodes. For example, more highly connected proteins are more
      likely to be lethal when knocked out. However, the correlation between lethality
      and connectivity is relatively weak, and some highly connected proteins can be
      removed without noticeable phenotypic effect. Similarly, network topology only
      weakly predicts the response of gene expression to environmental perturbations.
      Evolutionary simulations of gene-regulatory networks, presented here, suggest
      that such weak or non-existent correlations are to be expected, and are likely
      not due to inadequacy of experimental data. We argue that 'top-down' inferences
      of biological properties based on simple measures of network topology are of
      limited utility, and we present simulation results suggesting that much more
      detailed information about a gene's location in a regulatory network, as well as
      dynamic gene-expression data, are needed to make more meaningful functional and
      evolutionary predictions. Specifically, we find in our simulations that: (1) the
      relationship between a gene's connectivity and its fitness effect upon knockout
      depends on its equilibrium expression level; (2) correlation between connectivity
      and genetic variation is virtually non-existent, yet upon independent evolution
      of networks with identical topologies, some nodes exhibit consistently low or
      high polymorphism; and (3) certain genes show low polymorphism yet high
      divergence among independent evolutionary runs. This latter pattern is generally
      taken as a signature of positive selection, but in our simulations its cause is
      often neutral coevolution of regulatory inputs to the same gene.

PMID- 16897452
TI  - Mutation rate and pattern of microsatellites in common carp (Cyprinus carpio L.).
AB  - Microsatellites are popular molecular markers in genetic and evolutionary
      studies. Their mutational dynamics have been extensively studied in humans and
      fruit flies, but few data were available in fish. By genotyping 55 individuals of
      a F1 pedigree, we investigated the mutation rates and patterns of 49
      microsatellites in one of the most important fresh water fish species, the common
      carp (Cyprinus carpio L.). The overall mutation rate of the 49 loci was 5.56 x
      10(-4)/locus/generation (95% confidence interval 1.52 x 10(-4) and 1.63 x 10(
      3)). The change of allele size was between +2 to -5 repeat units, assuming that
      the mutation allele arose from the parental allele most similar in size to the
      mutant.

PMID- 16897453
TI  - The Micro-evolution of development.

PMID- 16897455
TI  - Identification and mapping of open chromatin regions within a 140 kb polygenic
      locus of human chromosome 19 using E. coli Dam methylase.
AB  - Using transient expression of the E. coli Dam methylase gene and analysis of the
      distribution of methylated GATC sites, we studied the distribution of open
      chromatin regions within a 140 kb long human genome segment in HEK-293 cells. Dam
      methylated sites were found in gene introns, exons, and intergenic regions, and
      their distribution along DNA was uneven. There were regions of high and low
      density of Dam methylated GATC sites, presumably corresponding to "open" and
      "closed" chromatin regions, respectively, and to the functional profile of the
      genomic locus under study. The Dam methylation profile was also generally in
      agreement with transcriptional activity of genes in the locus. Moreover, DNA
      regions accessible to Dam methylase apparently coincided with those
      hypersensitive to DNase I.

PMID- 16897454
TI  - Genetic population structure as indirect measure of dispersal ability in a Lake
      Tanganyika cichlid.
AB  - Diversification and speciation processes are influenced by intrinsic (ecological
      specialization, dispersal) and extrinsic (habitat structure and instability)
      factors, but the effect of ecological characteristics on dispersal is difficult
      to assess. This study uses mitochondrial control region sequences to investigate
      the population structure and demographic history of the endemic Lake Tanganyika
      cichlid Neolamprologus caudopunctatus with a preference for the rock-sand
      interface along two stretches of continuous, rocky shoreline, and across a sandy
      bay representing a potential dispersal barrier. Populations along uninterrupted
      habitat were not differentiated; whereas, the sandy bay separated two
      reciprocally monophyletic clades. The split between the two clades between
      170,000 and 260,000 years BP coincides with a period of rising water level
      following a major lowstand, and indicates that clades remained isolated
      throughout subsequent lake level fluctuations. Low long-term effective population
      sizes were inferred from modest genetic diversity estimates, and may be due to
      recent population expansions starting from small population sizes 45,000-60,000
      years BP. Comparisons with available data from specialized rock-dwelling species
      of the same area suggest that habitat structure and lake level fluctuations
      determine phylogeographic patterns on large scales, while fine-scale population
      structure and demography are modulated by species-specific ecologies.

PMID- 16897456
TI  - Population genetics of Collisella subrugosa (Patellogastropoda: Acmaeidae):
      evidence of two scales of population structure.
AB  - Marine invertebrate populations usually show high levels of genetic variability
      that has frequently been associated with spatial and temporal environmental
      heterogeneity. One of the most heterogeneous marine environments is the
      intertidal zone, the habitat of Collisella subrugosa, the most widespread and
      abundant Brazilian limpet. C. subrugosa has planktonic larvae that can disperse
      over long distances, what can promote gene flow among shores, working against
      interpopulational differentiation. In this study we investigated the genetic
      variability and populational substructure of C. subrugosa through analysis of 24
      allozyme loci in 14 samples (590 individuals) collected along 2,700 km of the
      Brazilian coast. The genetic variability was high ([Formula: see text] and
      [Formula: see text]), as expected for intertidal species. Genetic differentiation
      among samples was low (F (ST) = 0.03) what may reflect intensive gene flow
      associated with larval dispersal. However, we detected an isolation-by-distance
      pattern of population substructure in one sampled region. High levels of
      heterozygote deficiency were also observed for many loci in each sample.
      Alternative hypothesis are discussed, and the "breeding groups" is suggested to
      explain these pattern, indicating the main cause as environmental heterogeneity.

PMID- 16897457
TI  - The karyotypes of the thorny catfishes Wertheimeria maculata Steindachner, 1877
      and Hassar wilderi Kindle, 1895 (Siluriformes: Doradidae) and their relevance in
      doradids chromosomal evolution.
AB  - We studied the karyotypes of two doradids, the rare and endangered Wertheimeria
      maculata and a derived Amazonian species, Hassar wilderi. Cytogenetic
      characterization was assessed using conventional staining (Giemsa), C-banding,
      and NOR banding. Both species had 2n = 58 chromosomes but differed in their
      chromosome formulae, 24 m + 14sm + 8st + 12a for W. maculata and 32 m + 16sm +
      10st for H. wilderi. In W. maculata heterochromatin was mainly telomeric, and
      three chromosomes had a fully heterochromatic arm; in H. wilderi heterochromatin
      was also predominantly telomeric and evident in many more chromosomes. Hassar
      wilderi also presented one pair of homologues with a fully heterochromatic arm.
      In both species, nucleolar organizer regions were restricted to one pair of
      subtelocentric chromosomes. Assuming a basal position for W. maculata, we
      hypothesized that underlying conserved diploid and NOR-bearing chromosome
      numbers, chromosomal evolution in doradids has involved pericentric inversions
      and an increase of heterochromatic blocks.

PMID- 16897459
TI  - Wide distribution of related satellite DNA families within the genus Pimelia
      (Tenebrionidae).
AB  - Major satellites of species in the genus Pimelia comprise large portions of their
      genomes and belong to seven major satellite families which all originate from a
      common ancestral sequence. Here we present the results of comprehensive screening
      of 26 Pimelia species belonging to three distinct geographic groups (Ibero
      Balearic, African and Canary Islands) for the presence of different Pimelia
      satellite families in their genomes. Dot-blot hybridization experiments suggest
      that together with one dominant, highly abundant satellite family, other families
      are also present in genomes of the majority of examined Pimelia species, but as
      low-copy number repeats. The estimated abundance of these underrepresented
      repeats is about 4,000 copies per haploid genome. Signals of highly abundant
      satellite family from P. scabrosa (PSCA) in examined congeneric species, obtained
      after PCR amplification and Southern hybridization under high stringency
      conditions, corroborate sequence preservation of low-copy representatives of
      satellite families. PRINS localized low-copy repeats within the pericentromeric
      regions of all chromosomes. These results point to the existence of an extensive
      library of repetitive DNAs that was already present in the genome of the common
      ancestor of extant Pimelia taxa, and shifts the period of diversification of
      Pimelia satellites far in the history of this genus.

PMID- 16897458
TI  - Characterization of the satellite DNA Msat-160 from the species Chionomys nivalis
      (Rodentia, Arvicolinae).
AB  - The satellite DNA Msat-160 has been previously characterized in several species
      of the genus Microtus. Here we present the characterization of Msat-160 from
      Chionomys nivalis, a species with a very primitive karyotype. As in other
      Microtus species analyzed, C. nivalis Msat-160 is AT rich, has a monomer length
      of 160 bp, is undermethylated and is mainly located in all the pericentromeric
      heterochromatin of all autosomes and the X chromosome, but is completely absent
      from the Y chromosome. Hence, our results support the hypothesis that Msat-160
      was initially distributed in the pericentromeric heterochromatin of all autosomes
      and the X chromosome. The taxonomic status of the genus Chionomys in relation to
      the genus Microtus is a very interesting issue, so we constructed phylogenetic
      dendrograms using Msat-160 sequences from several Microtus species. Although the
      results were not informative about this issue, the presence of Msat-160 in C.
      nivalis and Microtus species suggested that both genera are closely related and
      that this satellite DNA was present in the common ancestor. Studies of Msat-160
      in different arvicoline species could help to determine the origin of this
      satellite and, perhaps, to establish the phylogenetic relationships of some
      arvicoline groups.

PMID- 16897460
TI  - Phylogenetic differentiation between Atlantic Scomber colias and Pacific Scomber
      japonicus based on nuclear DNA sequences.
AB  - In the classical taxonomy, three Scomber species are distinguished: S. scombrus,
      S. australasicus, and S. japonicus. Yet, some fish taxonomists have recently
      recognized Scomber colias, inhabiting the Atlantic Ocean, as a separate species
      from S. japonicus, distributed in the Pacific Ocean. Such proposal was based on
      significant mitochondrial DNA divergence as well as great phenotypic variation
      among individuals from these two ocean basins. However, in the absence of nuclear
      DNA data this issue remains still controversial. In this study, a phylogenetic
      analysis of nuclear 5S rDNA sequences was performed. A total of 30 individuals of
      S. colias collected in the Atlantic and 34 specimens of S. japonicus from the
      Pacific were characterized. Moreover, nine individuals of Pacific S.
      australasicus and eight of Atlantic S. scombrus were included. Maximum
      likelihood, maximum parsimony, and neighbor-joining analyses revealed the
      presence of two well-supported distinct clades corresponding to S. colias and S.
      japonicus, respectively. Altogether, morphologic and genetic data are in
      agreement with the recognition of two different species, S. colias in the
      Atlantic, and S. japonicus in the Pacific.

PMID- 16897461
TI  - The lamin Dm0 allele Ari3 acts as an enhancer of position effect variegation of
      the wm4 allele in Drosophila.
AB  - The association of lamin and lamin binding proteins with peripheral
      heterochromatin suggests the possibility that lamins may influence gene
      expression by participating in the epigenetic regulation of chromatin stucture.
      To test this hypothesis we have examined the effect of a recently generated
      partial loss-of-function lamin Dm0 allele Ari3 on PEV of the wm4 allele in the
      Drosophila eye. The Lam ( Ari3 ) allele is characterized by a truncation of the
      COOH-terminal domain and lacks the CaaX box that localizes lamin to the inner
      nuclear membrane. We show that the Lam ( Ari3 ) allele strongly increased
      silencing of wm4 expression, thus acting as an enhancer of PEV. These results
      indicate that lamins may be involved in regulating gene silencing and
      heterochromatic spreading at the wm4 locus and provide evidence that lamins may
      contribute to the regulation of higher-order chromatin organization.

PMID- 16897463
TI  - Comparative molecular population genetics of phycoerythrin locus in
      Prochlorococcus.
AB  - As the only remainder type of phycobiliproteins in Prochlorococcus, the actual
      role of phycoerythrin still remains unknown. Previous studies revealed that two
      different forms of phycoerythrin gene were found in two ecotypes of
      Prochlorococcus that are specifically adapted to either high light (HL) or low
      light (LL) conditions. Here we analyze patterns of phycoerythrin nucleotide
      variation in the HL- and LL-Prochlorococcus populations. Our analyses reveal a
      significantly greater number of non-synonymous fixed substitutions in peB and peA
      than expected based on interspecific comparisons. This pattern of excess non
      synonymous fixed substitutions is not seen in other five phycoerythrin-related
      genes (peZ/V/Y/T/S). Several neutrality statistical tests indicate an excess of
      rare frequency polymorphisms in the LL-Prochlorococcus data, but an excess of
      intermediate frequency polymorphisms in the HL-Prochlorococcus data.
      Distributions of the positively selected sites identified using the likelihood
      ratio test, when mapped onto the phycoerythrin tertiary structure, reveal that HL
      and LL-phycoerythrin should be under different selective patterns. These
      findings may provide insights into the likely role of selection at the
      phycoerythrin locus and motivate further research to unveil the function of
      phycoerythrin in Prochlorococcus.

PMID- 16897462
TI  - Sharing of transcription factors after gene duplication in the yeast
      Saccharomyces cerevisiae.
AB  - In a set of 190 duplicate gene pairs in yeast Saccharomyces cerevisiae, the
      sharing of transcription factors tended to decrease with increased divergence in
      coding sequence, at both synonymous and nonsynonymous sites. Our results showed a
      significantly higher sharing of transcription factors by duplicated gene pairs
      falling within duplicated genomic blocks than in other duplicated gene pairs; and
      genes in duplicated blocks also showed significantly greater conservation at the
      coding sequence level. In spite of the overall trends, there were certain gene
      pairs, both in duplicated blocks and in other genomic regions, which were highly
      divergent in coding sequence and yet had identical patterns of transcription
      factor binding. These results suggest that functional differentiation of genes
      after duplication is a multi-dimensional process, with different duplicate pairs
      differentiating in different ways.

PMID- 16897464
TI  - Characterization of the telomere regions of scleractinian coral, Acropora
      surculosa.
AB  - Terminal ends of vertebrate chromosomes are protected by tandem repeats of the
      sequence (TTAGGG). First thought to be vertebrate specific, (TTAGGG)( n ) has
      recently been identified in several aquatic invertebrates including sea urchin
      (Strongylocentrotus purpuratus), bay scallop (Argopecten irradians), and
      wedgeshell clam (Donax trunculus). We analyzed genomic DNA from scleractinian
      corals, Acropora surculosa, Favia pallida, Leptoria phrygia, and Goniastrea
      retiformis to determine the telomere sequence. Southern blot analysis suggests
      the presence of the vertebrate telomere repeats in all four species. Treatment of
      A. surculosa sperm DNA with Bal31 exonuclease revealed progressive shortening of
      the DNA fragments positive for the (TTAGGG)(22) sequence, supporting location of
      the repeats at the chromosome ends. The presence of the vertebrate telomere
      repeats in corals is evidence that the (TTAGGG)( n ) sequence is highly conserved
      among a divergent group of vertebrate and invertebrate species. Corals are
      members of the Lower Metazoans, the group of organisms that span the gap between
      the fungi and higher metazoans. Corals are the most basal organism reported to
      have the (TTAGGG)( n ) sequence to date, which suggests that the vertebrate
      telomere sequence may be much older than previously thought and that corals may
      share a number of genes with their higher relatives.

PMID- 16897465
TI  - State transitions revisited-a buffering system for dynamic low light acclimation
      of Arabidopsis.
AB  - The mobile part of the light-harvesting chlorophyll (chl) a/b protein complex
      (LHCII), composed of the Lhcb1 and Lhcb2 proteins, is the basic unit of
      chloroplast state transitions--the short term tuning system in balancing the
      excitation energy between Photosystem (PS) II and PSI. State transitions are
      catalysed by the thylakoid associated STN7 kinase, and we show here that besides
      the phosphorylation of the Lhcb1 and Lhcb2 proteins, also the phosphorylation of
      Lhcb4.2 (CP29) is under the control of the STN7 kinase. Upon growth of
      Arabidopsis WT and stn7 mutant plants under low and moderate light conditions,
      the WT plants favoured state 2 whereas stn7 was locked in state 1. The lack of
      the STN7 kinase and state transitions in stn7 also modified the thylakoid protein
      contents upon long-term low light acclimation resulting, for example, in low
      Lhcb1 and in elevated Lhca1 and Lhca2 protein amounts as compared to WT.
      Adjustments of thylakoid protein contents probably occurred at post
      transcriptional level since the DNA microarray experiments from each growth
      condition did not reveal any significant differences between stn7 and WT
      transcriptomes. The resulting high Lhcb2/Lhcb1 ratio in stn7 upon growth at low
      light was accompanied by lower capacity for NPQ than in WT. On the contrary,
      higher amounts of PsbS in stn7 under moderate and high light growth conditions
      resulted in higher NPQ compared to WT and consequently also in a protection of
      PSII against photoinhibition. STN7 kinase and the state transitions are suggested
      to have a physiological significance for dynamic acclimation to low but
      fluctuating growth light conditions. They are shown to function as a buffering
      system upon short high light illumination peaks by shifting the thylakoids from
      state 2 to state 1 and thereby down regulating the induction of stress-responsive
      genes, a likely result from transient over-reduction of PSI acceptors.

PMID- 16897466
TI  - Linear molecules of tobacco ptDNA end at known replication origins and additional
      loci.
AB  - Higher plant plastid DNA (ptDNA) is generally described as a double-stranded
      circular molecule of the size of the monomer of the plastid genome. Also, the
      substrates and products of ptDNA replication are generally assumed to be circular
      molecules. Linear or partly linear ptDNA molecules were detected in our present
      study using pulsed-field gel electrophoresis and Southern blotting of ptDNA
      restricted with 'single cutter' restriction enzymes. These linear DNA molecules
      show discrete end points which were mapped using appropriate probes. One possible
      explanation of discrete ends would be that they represent origins of replication.
      Indeed, some of the mapped ends correlate well with the known origins of
      replication of tobacco plastids, i.e. both of the oriA sequences and--less
      pronouncedly--with the oriB elements. Other ends correspond to replication
      origins that were described for Oenothera hookeri, Zea mays, Glycine max and
      Chlamydomonas reinhardtii, respectively, while some of the mapped ends were not
      described previously and might therefore represent additional origins of
      replication.

PMID- 16897467
TI  - DEA1, a circadian- and cold-regulated tomato gene, protects yeast cells from
      freezing death.
AB  - Cold and freezing damage to plants can be mitigated by inducible factors during
      an acclimation period. DEA1 is a circadian-regulated tomato (Solanum
      lycopersicum) gene with sequence similarity to EARLI1, an Arabidopsis thaliana
      gene that confers cold protection. To investigate whether DEA1 was responsive to
      environmental variables such as cold, cold-treated tomatoes were analyzed for
      DEA1 expression. DEA1 transcript accumulated in response to cold, and the
      rapidity of the cold-induced transcript accumulation was regulated by the
      circadian rhythm. To test whether DEA1 could protect cells from freezing damage,
      we transformed the yeast, Pichia pastoris, with an inducible DEA1 construct.
      Yeast cells transformed with the gene survived freezing at a significantly higher
      rate than control strains and a strain expressing the LacZ gene. Transgenic
      tomato plants over-expressing or knocking down DEA1 transcript levels did not
      have an altered phenotype with respect to cold- or pathogen-susceptibility
      relative to control plants.

PMID- 16897468
TI  - Global analysis of gene expression during development and ripening of citrus
      fruit flesh. A proposed mechanism for citric Acid utilization.
AB  - Microarrays of cDNA have been used to examine expression changes of 7000 genes
      during development and ripening of the fruit flesh of self-incompatible Citrus
      clementina, a non-climateric species. The data indicated that 2243 putative
      unigenes showed significant expression changes. Functional classification
      revealed that genes encoding for regulatory proteins were significantly
      overrepresented in the up-regulated gene clusters. The transcriptomic study
      together with the analyses of selected metabolites highlighted key physiological
      processes occurring during citrus fruit development and ripening such as water
      accumulation, carbohydrate build-up, acid reduction, pigment substitutions
      (carotenoid accumulation and chlorophyll decreases) and ascorbic acid diminution.
      Often, the combined analyses strongly suggested prevalence of specific metabolic
      alternatives. This observation has been exemplified with the proposal for a
      mechanism for citrate utilization, a process of much importance in citrus
      industry. Microarray data validated by real-time RT-PCR suggested that citrate
      was sequentially metabolyzed to isocitrate, 2-oxoglutarate and glutamate.
      Thereafter, glutamate was both utilized for glutamine production and catabolyzed
      through the gamma-aminobutirate (GABA) shunt (GABA --> succinate semialdehyde -->
      succinate). This last observation appears to be of special relevance since it
      links the proton consuming reaction glutamate + H(+)--> GABA + CO(2) with high
      acid levels. GG-MS determinations showed that glutamate was constant while GABA
      levels decreased at ripening in agreement with a feasible activation of the GABA
      shunt during acid catabolism. This suggestion provides a convincing explanation
      for the strong reduction of both citrate and cytoplasmatic acidity that takes
      place in citrus fruit flesh during development and ripening.

PMID- 16897469
TI  - The Arabidopsis Bio2 protein requires mitochondrial targeting for activity.
AB  - Mitochondria are involved in the production of various vitamins, such as biotin,
      in plants. It is unclear why these biosynthetic pathways have been maintained
      partly or entirely within the mitochondria throughout evolution. The last step in
      biotin biosynthesis occurs within the mitochondria and is catalyzed by the biotin
      synthase complex containing the BIO2 gene product. We investigated whether the
      Arabidopsis Bio2 enzyme could function outside mitochondria, by trying to
      complement a bio2 mutant with a truncated version of BIO2 lacking the region
      encoding the mitochondrial targeting sequence. We describe the characterization
      of a new T-DNA allele of bio2, with the sole phenotype of an absence of biotin
      production, in contrast to the previously characterized EMS bio2 allele (Patton
      et al. 1998, Plant Physiol 116(3):935-946). We found that a cytosolic version of
      the Bio2 protein could not complement this mutant. Supplementation with the
      substrate dethiobiotin (DTB) also failed to rescue the mutant phenotype. Thus,
      the lack of availability of DTB in the cytosol is not the only factor preventing
      this reaction from occurring outside mitochondria. Bio2 requires mitochondrial
      targeting for activity, enabling it to fulfill its role in biotin synthesis. The
      reaction catalyzed by Bio2 may be subject to biochemical constraints, and the
      apparent close connection with the mitochondrial Fe-S machinery may account for
      the reaction being retained within the organelle.

PMID- 16897470
TI  - RTS, a rice anther-specific gene is required for male fertility and its promoter
      sequence directs tissue-specific gene expression in different plant species.
AB  - A tapetum-specific gene, RTS, has been isolated by differential screening of a
      cDNA library from rice panicles. RTS is a unique gene in the rice genome. RNA
      blot analysis and in situ hybridization indicates that this gene is predominantly
      expressed in the anther's tapetum during meiosis and disappears before anthesis.
      RTS has no introns and encodes a putative polypeptide of 94 amino acids with a
      hydrophobic N-terminal region. The nucleotide and deduced amino acid sequence of
      the gene do not show significant homology to any known sequences. However, a
      sequence in the promoter region, GAATTTGTTA, differs only by one or two
      nucleotides from one of the conserved motifs in the promoter region of two pollen
      specific genes of tomato. Several other sequence motifs found in other anther
      specific promoters were also identified in the promoter of the RTS gene.
      Transgenic and antisense RNA approaches revealed that RTS gene is required for
      male fertility in rice. The promoter region of RTS, when fused to the Bacillus
      amyloliquefaciens ribonuclease gene, barnase, or the antisense of the RTS gene,
      is able to drive tissue-specific expression of both genes in rice, creeping
      bentgrass (Agrostis stolonifera L.) and Arabidopsis, conferring male sterility to
      the transgenic plants. Light and near-infrared confocal microscopy of cross
      sections through developing flowers of male-sterile transgenics shows that tissue
      specific expression of barnase or the antisense RTS genes interrupts tapetal
      development, resulting in deformed non-viable pollen. These results demonstrate a
      critical role of the RTS gene in pollen development in rice and the versatile
      application of the RTS gene promoter in directing anther-specific gene expression
      in both monocotyledonous and dicotyledonous plants, pointing to a potential for
      exploiting this gene and its promoter for engineering male sterility for hybrid
      production of various plant species.

PMID- 16897471
TI  - The ACC synthase TOE sequence is required for interaction with ETO1 family
      proteins and destabilization of target proteins.
AB  - The Arabidopsis ETO1 protein is a negative regulator of ethylene biosynthesis. It
      specifically inhibits the enzyme activity of type 2 1-aminocyclopropane-1
      carboxylate synthases (ACC synthases or ACS) and promotes their degradation by a
      proteasome-dependent pathway. To further understand the function of the ETO1
      family in the plant kingdom, we cloned a cDNA of LeEOL1 (Lycopersicon esculentum
      ETO 1- LIKE 1), an ETO1 homolog from tomato. LeEOL1 encodes a putative protein
      with domain architecture conserved in the Arabidopsis ETO1/EOL1/EOL2 proteins and
      in the predicted rice EOL proteins. LeEOL1 is expressed in leaf, stem, root,
      flower, and the full ripe stage of fruit, suggesting diverse regulatory roles in
      the development of tomato. Yeast two-hybrid analysis revealed specific
      interactions between LeEOL1 and type 2 ACC synthases. When the C-terminal 14
      amino acids (TOE; target of ETO1) of LE-ACS3 specific to type 2 ACC synthases
      were fused to a type 1 ACS, LE-ACS2, at the corresponding position, it allowed LE
      ACS2 to strongly interact with LeEOL1. A GFP-TOE(LE-ACS3) fusion protein
      expressed in rice calli and in the roots of wild-type Arabidopsis showed reduced
      stability compared to native GFP. However, the fluorescence of GFP-TOE(LE-ACS3)
      was comparable to that of the native GFP in Arabidopsis eto1-4 mutant.
      Furthermore, MG132 treatment significantly enhanced the fluorescence of GFP
      TOE(LE-ACS3) in the roots of wild-type Arabidopsis. These results suggest that
      the ETO1-family-mediated ACS protein degradation pathway is conserved in both
      monocots and dicots, and that TOE acts as a protein destabilization signal
      recognized by the ETO1 protein family.

PMID- 16897472
TI  - ASK1, a SKP1 homolog, is required for nuclear reorganization, presynaptic homolog
      juxtaposition and the proper distribution of cohesin during meiosis in
      Arabidopsis.
AB  - Nuclear reorganization and juxtaposition of homologous chromosomes at late
      leptotene/early zygotene are essential steps before chromosome synapsis at
      pachytene. We report the results of detailed studies, which demonstrate that
      nuclear reorganization and homolog juxtapositioning processes are defective in a
      null mutant, ask1-1. Our results from 4, 6-diamino-2-phenylindole (DAPI)-stained
      spreads showed that the "synizetic knot", which is typically found in wild type
      (WT) meiosis during late leptotene and zygotene, was missing in the ask1-1
      mutant. Furthermore, ask1-1 meiocytes exhibited only limited homolog
      juxtaposition at centromere regions at early zygotene. Immunodetection of the
      cohesin protein SYN1 identified ask1 defects in cohesin distribution from
      zygotene to anaphase I. Analysis of meiotic chromosomes in ask1-1 and syn1 single
      mutants, as well as an ask1-1 syn1 double mutant indicate that ASK1 is required
      for normal SYN1 distribution during meiotic prophase I and suggest that ask1
      associated defects may be primarily related to SYN1 mislocalization.

PMID- 16897473
TI  - Spatial and temporal organization of sucrose metabolism in Lotus japonicus
      nitrogen-fixing nodules suggests a role for the elusive alkaline/neutral
      invertase.
AB  - Symbiotic nitrogen fixation (SNF) in legume nodules is a highly energy demanding
      process, fuelled by plant-supplied carbohydrates mainly in the form of sucrose.
      In this study, we have combined molecular and biochemical approaches in order to
      study the spatial and temporal organisation of sucrose metabolism in nitrogen
      fixing nodules of the model legume Lotus japonicus, with an emphasis on the
      neglected role of alkaline/neutral invertase. For this purpose, a full-length
      cDNA clone coding for an alkaline/neutral invertase isoform, termed LjInv1, was
      identified in a L. japonicus mature nodule cDNA libraries. Alkaline/neutral
      invertase activity was also found to be the predominant invertase activity in
      mature nodules. Real-time reverse-transcription polymerase chain reaction
      analysis was used in order to study the temporal expression patterns of LjInv1 in
      parallel with genes encoding acid invertase and sucrose synthase (SuSy) isoforms,
      and enzymes involved in the subsequent hexose partitioning including hexokinase,
      phosphoglucomutase (PGM) and phosphoglucose isomerase (PGI). The spatial
      organisation of sucrose metabolism was studied by in situ localisation of LjInv1
      transcripts and alkaline/neutral invertase activity, and SuSy protein during
      nodule development. Furthermore, the spatial organisation of hexose metabolism
      was investigated by histochemical localisation of hexokinase, PGM and PGI
      activities in mature nodules. The results considered together indicate that
      alkaline/neutral invertase could contribute to both the Glc-1-P and Glc-6-P pools
      in nodules, fuelling both biosynthetic processes and SNF. Furthermore, transcript
      profiling analysis revealed that genes coding for hexokinase and putative
      plastidic PGM and PGI isoforms are upregulated during the early stages of nodule
      development, while the levels of transcripts corresponding to cytosolic PGM and
      PGI isoforms remained similar to uninfected roots, indicating a possible role of
      LjInv1 in producing hexoses for starch production and other biosynthetic
      processes in developing nodules.

PMID- 16897474
TI  - Identification and characterization of PiORP1, a Petunia oxysterol-binding
      protein related protein involved in receptor-kinase mediated signaling in pollen,
      and analysis of the ORP gene family in Arabidopsis.
AB  - Oxysterol-binding proteins (OSBPs) and oxysterol-binding-protein related proteins
      (ORPs) are encoded by most eukaryotic genomes examined to date; however, they
      have not yet been characterized in plants. Here we report the identification and
      characterization of PiORP1, an ORP of Petunia inflata that interacts with the
      cytoplasmic kinase domain of a receptor-like kinase, named PRK1, of P. inflata.
      PiORP1 is phosphorylated by PRK1 in vitro and therefore may be involved in PRK1
      signaling during pollen development and growth. RNA gel blot analysis showed that
      PiORP1 and PRK1 had very similar expression patterns in developing pollen, mature
      pollen and pollen tubes. GFP fusion proteins of PiORP1 localized in the plasma
      membrane of pollen tubes at distinct foci and its PH domain alone was sufficient
      to mediate this localization. The sequence for the oxysterol-binding domain of
      PiORP1 was used to search the genome of Arabidopsis; 12 ORPs were identified and
      phylogenetic analysis revealed that they fell into two distinct clades,
      consistent with the ORPs of other eukaryotes. RT-PCR analysis showed that all 12
      Arabidopsis ORPs were expressed; 10 were expressed in most of the tissues
      examined under normal growth conditions, but only three were expressed in pollen.

PMID- 16897475
TI  - A Psb27 homologue in Arabidopsis thaliana is required for efficient repair of
      photodamaged photosystem II.
AB  - Psb27 has been identified as a lumenal protein associated with photosystem II
      (PSII). To gain insight into the function of Psb27, we isolated a mutant
      Arabidopsis plant with a loss of psb27 function. The quantity of PSII complexes
      and electron transfer within PSII remained largely unaffected in the psb27
      mutant. Our results also showed that under high-light-illumination, PSII activity
      and the content of the PSII reaction center protein D1 decreased more
      significantly in the psb27 mutant than in wild-type (WT) plant. Treatment of
      leaves with a chloroplast protein synthesis inhibitor resulted in similar light
      induced PSII inactivation levels and D1 protein degradation rates in the WT and
      psb27 mutant plants. Recovery of PSII activity after photoinhibition was delayed
      in the psb27 mutant, suggesting that Psb27 is required for efficient recovery of
      the photodamaged PSII complex. Overall, these results demonstrated that Psb27 in
      Arabidopsis is not essential for oxygenic photosynthesis and PSII formation.
      Instead, our results provide evidence for the involvement of this lumenal protein
      in the recovery process of PSII.

PMID- 16897476
TI  - Suppression of gene expression of a recessive SP11/SCR allele by an untranscribed
      SP11/SCR allele in Brassica self-incompatibility.
AB  - Mutations in the S locus of a self-compatible cultivar Yellow Sarson in Brassica
      rapa, which has a self-compatible class-I S haplotype, S-f2, were investigated. S
      28 in Brassica oleracea was found to be a member of an interspecific pair with S
      f2 in B. rapa. The original S haplotype of S-f2 was identified to be S-54 in B.
      rapa. Sequence comparison of alleles in S-f2 with those in S-54 and B. oleracea S
      28 revealed insertion of a retrotransposon-like sequence in the first intron of
      SRK and 89-bp deletion in the promoter region of SP11. No transcripts of SRK and
      SP11 were detected in S-f2 homozygotes, suggesting that the insertion and the
      deletion in SRK and SP11, respectively, caused the loss of the function of these
      genes. Promoter assay using transgenic plants indicated that the SP11 promoter of
      S-f2 has no activity. Heterozygotes of S-f2 and a normal class-II S haplotype, S
      60, in B. rapa were found to be self-compatible. Interestingly, transcription of
      SP11-60 was revealed to be suppressed in the S-f2/S-60 heterozygotes, suggesting
      that an untranscribed class-I SP11 allele suppresses the expression of a
      recessive class-II SP11 allele in the anthers of S heterozygotes. Similar
      phenomenon was observed in heterozygotes of a self-compatible class-I S haplotype
      and a self-incompatible class-II S haplotype in B. oleracea.

PMID- 16897477
TI  - Distinct developmental defense activations in barley embryos identified by
      transcriptome profiling.
AB  - Proper embryo development is crucial for normal growth and development of barley.
      Numerous related aspects of this process--for example how the embryo establishes
      and sustains disease resistance for extended periods during dormancy--remain
      largely unknown. Here we report the results of microarray analyses of >22,000
      genes, which together with measurements of jasmonic acid and salicylic acid
      during embryo development provide new information on the initiation in the
      developing barley embryo of at least two distinct types of developmental defense
      activation (DDA). Early DDA is characterized by the up-regulation of a specific
      set of genes around 20 days after flowering, including co-regulation of those for
      encoding 9-lipoxygenase and several oxylipin-generating enzymes, possibly leading
      to the formation of alpha-ketols. The same developmental phase includes an up
      regulation of several defense genes, and indications of co-regulation of those
      for enzymes involved in the generation of phenylpropanoid phytoalexins. Late DDA
      is initiated prior to grain desiccation, around 37 days after flowering, with up
      regulation of several genes encoding proteins with roles in antioxidant responses
      as well as a simultaneous up-regulation of several PR genes is notable.
      Throughout barley embryo development, there are no indications of an increased
      biosynthesis of either jasmonic acid or salicylic acid. Collectively, the results
      help explain how the proposed DDA enables protection of the developing barley
      embryo and grain for purposes of disease resistance.

PMID- 16897478
TI  - Targeted Ds-tagging strategy generates high allelic diversity at the Arabidopsis
      HY2 locus.
AB  - The targeted (or directed) tagging is a strategy aimed to mobilize a tranposon
      into a specific gene (target). Only a very few Arabidopsis genes have been tagged
      by this way, thus the efficiency of the strategy, as well as the diversity of the
      alleles obtained are not well documented. We have used a maize Ds element in a
      directed tagging of HY2. The starting Ds element, located 22 kb proximal to HY2,
      has been remobilized in a cross with an Ac transposase source line. From the F2
      progeny of 4800 F1 we phenotypically isolated seven hy2 mutants. Molecular
      analysis of these alleles revealed that two contained a Ds element in HY2 and
      were instable, three have a large deletion that partially or completely removed
      HY2, one has a footprint in a HY2 exon and one leaky allele consisted of a 22 kb
      inversion upstream the HY2 coding sequence. Thus, the transposon-based directed
      tagging strategy generates a wide diversity of tagged and non-tagged alleles that
      can be used to generate allelic series or deletion of clustered genes.

PMID- 16897479
TI  - Germin-like genes are expressed during somatic embryogenesis and early
      development of conifers.
AB  - Germins and germin-like proteins (GLPs) are members of a superfamily of proteins
      widely distributed in plants. Their localization within the extracellular matrix
      and in some cases their hydrogen peroxide-producing activity suggests that these
      proteins are involved in cell wall metabolism during stress responses and
      developmental processes. Several very highly conserved conifer GLPs have been
      identified in somatic embryo tissues. In order to gain more knowledge on their
      potential involvement in the development of this particular tissue, we have
      characterized a new GLP gene, LmGER1 in hybrid larch. Anti-GLP immunserum and in
      gel activity analyses suggested the presence of superoxide dismutase activity in
      apoplastic proteins from larch somatic embryos. These results could indicate a
      possible role for LmGER1 in this physiological process. The expression of LmGER1
      has been followed during the maturation of somatic embryos and in different
      organs of young plantlets by homologous transformation with a promoter-gus
      construct. This promoter was activated in the root cap of young embryos and,
      later on, in the cotyledons and in the vascular procambium and xylem.
      Furthermore, the importance of this gene in embryo development was evaluated by
      transforming embryonal masses with a gene construct encoding a hairpin RNA
      leading to gene silencing. The potential role of LmGER1 in cross-linking of cell
      wall components is discussed.

PMID- 16897480
TI  - Plant coenzyme A biosynthesis: characterization of two pantothenate kinases from
      Arabidopsis.
AB  - In bacterial and animal coenzyme A (CoA) biosynthesis, pantothenate kinase (PANK)
      activity is critical in regulating intracellular CoA levels. Less is known about
      the role of PANK in plants, although a single plant isozyme from Arabidopsis,
      AtPANK1, was previously cloned and analyzed in vitro. We report here the
      characterization of a second pantothenate kinase of Arabidopsis, AtPANK2, as well
      as characterization of the physiological roles of both plant enzymes. The
      activity of the second pantothenate kinase, AtPANK2, was confirmed by its ability
      to complement the temperature-sensitive mutation of the bacterial pantothenate
      kinase in E. coli strain ts9. Knock-out mutation of either AtPANK1 or AtPANK2 did
      not inhibit plant growth, whereas pank1-1/pank2-1 double knockout mutations were
      embryo lethal. The phenotypes of the mutant plants demonstrated that only one of
      the AtPANK enzymes is necessary and sufficient for producing adequate CoA levels,
      and that no other enzyme can compensate for the loss of both isoforms. Real-time
      PCR measurements of AtPANK1 and AtPANK2 transcripts indicated that both enzymes
      are expressed with similar patterns in all tissues examined, further suggesting
      that AtPANK1 and AtPANK2 have complementary roles. The two enzymes have
      homologous pantothenate kinase domains, but AtPANK2 also carries a large C
      terminal protein domain. Sequence comparisons indicate that this type of
      "bifunctional" pantothenate kinase is conserved in other higher eukaryotes as
      well. Although the function of the C-terminal domain is not known, homology
      structure modeling suggests it contains a highly conserved cluster of charged
      residues that likely constitute a metal-binding site.

PMID- 16897482
TI  - Chromatin immunoprecipitation analysis of the tobacco PR-1a- and the truncated
      CaMV 35S promoter reveals differences in salicylic acid-dependent TGA factor
      binding and histone acetylation.
AB  - Salicylic acid (SA) is a plant signalling molecule needed for the induction of
      defence responses upon attack by a variety of pathogens. Truncation of the
      Cauliflower Mosaic Virus (CaMV) 35S promoter down to 90 bp has identified
      activation sequence-1 (as-1) as an autonomous SA-responsive cis element. The as-1
      like elements are found in a number of SA-inducible promoters like e.g. the
      tobacco PR-1a promoter. They are recognized by basic/leucine zipper (bZIP)
      transcription factors of the TGA family. In tobacco leaves, TGA2.2 is the most
      abundant TGA factor. TGA2.2 is required for the expression of as-1-containing
      promoters. Here we unravel clear differences between the "truncated" CaMV 35S and
      the PR-1a promoter with respect to in vivo TGA binding and histone acetylation.
      Chromatin immunoprecipitation (ChIP) analysis revealed SA-inducible recruitment
      of tobacco TGA2.2 as well as SA-inducible histone acetylation at the PR-1a
      promoter. In contrast, no influence of SA on TGA2.2 binding and histone
      acetylation was detectable at the "truncated" CaMV 35S promoter. The finding of
      SA-independent TGA factor binding in the absence of additional flanking
      regulatory sequences suggests that transcriptional activation is not necessarily
      mediated by inducible DNA binding of TGA factors. Plants with severely reduced
      TGA2.2 protein levels also showed SA-induced histone acetylation at the PR-1a
      promoter indicating that regulatory events independent from TGA2.2 function are
      initiated at the PR-1a promoter.

PMID- 16897481
TI  - Identification of a dehydration and ABA-responsive promoter regulon and isolation
      of corresponding DNA binding proteins for the group 4 LEA gene CpC2 from C.
      plantagineum.
AB  - The resurrection plant Craterostigma plantagineum (Scrophulariaceae) is used as a
      model system to investigate the molecular and biochemical basis of desiccation
      tolerance. Genes which contribute to desiccation tolerance are expressed during
      dehydration of this plant. One of the dehydration-induced genes is CpC2, a group
      4 LEA gene. The CpC2 promoter was analysed and a core promoter region (CPR) was
      identified which is critical for the responsiveness of the gene to dehydration
      and the plant hormone ABA. The CPR motif contains two ABA-response elements
      (ABRE) and a binding site for HDZIP transcription factors. A yeast one-hybrid
      screen was performed to isolate CPR binding proteins. This resulted in the
      isolation of a bZIP transcription factor (CpbZIP1) and three highly conserved
      CpHistone H3 proteins. Two of these CpHistone H3 proteins are constitutively
      expressed histone H3 variants which are suggested to be involved in gene
      regulation via histone modification. The CpbZIP1 belongs to the group S of bZIP
      genes which possess long 5'-UTRs with a putative regulatory function. A second
      very similar bZIP clone, CpbZIP2, was isolated which contains a conserved small
      upstream open reading frame (uORF) within the 5'-leader sequence. A possible
      regulatory role of the uORF is discussed.

PMID- 16897483
TI  - Two highly divergent alcohol dehydrogenases of melon exhibit fruit ripening
      specific expression and distinct biochemical characteristics.
AB  - Alcohol dehydrogenases (ADH) participate in the biosynthetic pathway of aroma
      volatiles in fruit by interconverting aldehydes to alcohols and providing
      substrates for the formation of esters. Two highly divergent ADH genes (15%
      identity at the amino acid level) of Cantaloupe Charentais melon (Cucumis melo
      var. Cantalupensis) have been isolated. Cm-ADH1 belongs to the medium-chain zinc
      binding type of ADHs and is highly similar to all ADH genes expressed in fruit
      isolated so far. Cm-ADH2 belongs to the short-chain type of ADHs. The two encoded
      proteins are enzymatically active upon expression in yeast. Cm-ADH1 has strong
      preference for NAPDH as a co-factor, whereas Cm-ADH2 preferentially uses NADH.
      Both Cm-ADH proteins are much more active as reductases with K (m)s 10-20 times
      lower for the conversion of aldehydes to alcohols than for the dehydrogenation of
      alcohols to aldehydes. They both show strong preference for aliphatic aldehydes
      but Cm-ADH1 is capable of reducing branched aldehydes such as 3
      methylbutyraldehyde, whereas Cm-ADH2 cannot. Both Cm-ADH genes are expressed
      specifically in fruit and up-regulated during ripening. Gene expression as well
      as total ADH activity are strongly inhibited in antisense ACC oxidase melons and
      in melon fruit treated with the ethylene antagonist 1-methylcyclopropene (1-MCP),
      indicating a positive regulation by ethylene. These data suggest that each of the
      Cm-ADH protein plays a specific role in the regulation of aroma biosynthesis in
      melon fruit.

PMID- 16897484
TI  - Effects of postharvest storage and dormancy status on ABA content, metabolism,
      and expression of genes involved in ABA biosynthesis and metabolism in potato
      tuber tissues.
AB  - At harvest, and for an indeterminate period thereafter, potato tubers will not
      sprout and are physiologically dormant. Abscisic acid (ABA) has been shown to
      play a critical role in tuber dormancy control but the mechanisms controlling ABA
      content during dormancy as well as the sites of ABA synthesis and catabolism are
      unknown. As a first step in defining the sites of synthesis and cognate processes
      regulating ABA turnover during storage and dormancy progression, gene sequences
      encoding the ABA biosynthetic enzymes zeaxanthin epoxidase (ZEP) and 9-cis
      epoxycarotenoid dioxygenase (NCED) and three catabolism-related genes were used
      to quantify changes in their relative mRNA abundances in three specific tuber
      tissues (meristems, their surrounding periderm and underlying cortex) by qRT-PCR.
      During storage, StZEP expression was relatively constant in meristems, exhibited
      a biphasic pattern in periderm with transient increases during early and mid-to
      late-storage, and peaked during mid-storage in cortex. Expression of two members
      of the potato NCED gene family was found to correlate with changes in ABA content
      in meristems (StNCED2) and cortex (StNCED1). Conversely, expression patterns of
      three putative ABA-8'-hydroxylase (CYP707A) genes during storage varied in a
      tissue-specific manner with expression of two of these genes rising in meristems
      and periderm and declining in cortex during storage. These results suggest that
      ABA synthesis and metabolism occur in all tuber tissues examined and that tuber
      ABA content during dormancy is the result of a balance of synthesis and
      metabolism that increasingly favors catabolism as dormancy ends and may be
      controlled at the level of StNCED and StCYP707A gene activities.

PMID- 16897485
TI  - Comparative analysis of expressed sequences reveals a conserved pattern of
      optimal codon usage in plants.
AB  - Codon usage bias is a ubiquitous phenomenon, which may be caused by mutational
      bias, selection, or both. The patterns of codon usage in plants are not well
      understood. Datasets of expressed sequence tags (ESTs) available for many plant
      species provide the resources for large-scale comparative analysis of codon usage
      patterns. We developed a computational approach to translate EST or assembled
      contig sequences, and then used the coding information for comparative analysis
      of codon usage in 12 plant species, including 6 eudicots, 5 monocots and the
      green alga Chlamydomonas reinhardtii. While codon nucleotide composition is
      highly conserved within eudicots or monocots, there is a significant difference
      between these two major taxonomic groups of higher plants. The third nucleotide
      position of codons is AU-rich in the eudicot genomes (35-42% of G+C content), but
      GC-rich in the monocot genomes (59-61% of G+C content). To identify optimal
      codons in these species, we used EST counts to estimate gene transcript levels.
      It was demonstrated that codon usage bias is correlated positively with gene
      transcript levels. Interestingly, the use of optimal codons appears to be well
      conserved between eudicots and monocots, and to a lesser degree between the
      higher plants and C. reinhardtii. Most of the optimal codons end with a C or G
      base, regardless of the different nucleotide composition in these genomes. The
      results suggest that plant codon usage is affected by translational selection,
      and the selective pressure appears to be conserved in the plant kingdom.

PMID- 16897486
TI  - Gene activation in plastids by the CRE site-specific recombinase.
AB  - We developed a novel system for gene activation in plastids that uses the
      CRE/loxP site-specific recombination system to create a translatable reading
      frame by excision of a blocking sequence. To test the system, we introduced an
      inactive gfp* gene into the tobacco plastid genome downstream of the selectable
      spectinomcyin resistance (aadA) marker gene. The aadA gene is the blocking
      sequence, and is flanked by directly oriented loxP sites for excision by the CRE.
      In the non-activated state, gfp* is transcribed from the aadA promoter, but the
      mRNA is not translated due to the lack of an AUG translation initiation codon.
      Green Fluorescent Protein (GFP) expression is activated by excision of the aadA
      coding segment to link up the gfp* coding region with the translation initiation
      codon of aadA. Tobacco plants that carry the inactive gfp* gene do not contain
      detectable levels of GFP. However, activation of gfp* resulted in GFP
      accumulation, proving the utility of CRE-induced protein expression in tobacco
      chloroplasts. The gene activation system described here will be useful to probe
      plastid gene function and for the production of recombinant proteins in
      chloroplasts.

PMID- 16897487
TI  - Cloning, characterization and localization of three novel class III peroxidases
      in lignifying xylem of Norway spruce (Picea abies).
AB  - Plant class III peroxidases (POXs) take part in the formation of lignin and
      maturation of plant cell walls. However, only a few examples of such peroxidases
      from gymnosperm tree species with highly lignified xylem tracheids have been
      implicated so far. We report here cDNA cloning of three xylem-expressed class III
      peroxidase encoding genes from Norway spruce (Picea abies). The translated
      proteins, PX1, PX2 and PX3, contain the conserved amino acids required for heme
      binding and peroxidase catalysis. They all begin with putative secretion signal
      propeptide sequences but diverge substantially at phylogenetic level, grouping to
      two subclusters when aligned with other class III plant peroxidases. In situ
      hybridization analysis on expression of the three POXs in Norway spruce seedlings
      showed that mRNA coding for PX1 and PX2 accumulated in the cytoplasm of young,
      developing tracheids within the current growth ring where lignification is
      occurring. Function of the putative N-terminal secretion signal peptides for PX1,
      PX2 and PX3 was confirmed by constructing chimeric fusions with EGFP (enhanced
      green fluorescent protein) and expressing them in tobacco protoplasts. Full
      length coding region of px1 was also heterologously expressed in Catharanthus
      roseus hairy root cultures. Thus, at least the spruce PX1 peroxidase is processed
      via the endoplasmic reticulum (ER) most likely for secretion to the cell wall.
      Thereby, PX1 displays correct spatiotemporal localization for participation in
      the maturation of the spruce tracheid secondary cell wall.

PMID- 16897489
TI  - Regulation of the kinase activity of the MIK GCK-like MAP4K by alternative
      splicing.
AB  - Alternative splicing of introns is essential to ensure the complexity of
      mammalian genome functions. In particular, the generation of a high number of
      different isoforms by alternative splicing is an important characteristic of
      genes coding for signalling proteins such as mitogen activated protein kinases
      (MAPKs). This is thought to allow these proteins to transduce multiple stimuli in
      a highly regulated manner. Plant genes are also subjected to alternative
      splicing. Nevertheless, clear examples of the functional consequences of this
      phenomenon are still scarce in plants. MIK is a maize gene coding for a GCK-like
      MAP4K that can be activated by interaction with maize atypical receptor kinase
      (MARK), an atypical receptor kinase. Here we show that MIK is subjected to
      alternative splicing. Expression of MIK leads to, at least, 4 different mature
      mRNAs that accumulate with particular expression profiles during maize
      development. Our results show that the polypeptides encoded by the different MIK
      mRNAs display different kinase activity and are differentially activated by
      interaction with the MARK receptor. Two MIK isoforms display constitutive kinase
      activity, one isoform is inactive but can be activated by MARK, and the fourth
      MIK isoform is inactive and cannot be activated by MARK. Our results constitute a
      clear example of the biochemical consequences of alternative splicing in plants.
      The selective conservation during evolution of the intron-exon structure of the
      region coding for the regulator domain of MIK, as well as the maintenance in
      maize, rice and Arabidopsis of the alternative splicing of some of these introns,
      are strong indications of its functional importance.

PMID- 16897488
TI  - Heat stress-induced H(2)O (2) is required for effective expression of heat shock
      genes in Arabidopsis.
AB  - The mechanisms of sensing and signalling of heat and oxidative stresses are not
      well understood. The central question of this paper is whether in plant cells
      oxidative stress, in particular H(2)O(2), is required for heat stress- and heat
      shock factor (HSF)-dependent expression of genes. Heat stress increases
      intracellular accumulation of H(2)O(2) in Arabidopsis cell culture. The
      accumulation was greatly diminished using ascorbate as a scavenger or
      respectively diphenyleneiodonium chloride (DPI) as an inhibitor of reactive
      oxygen species production. The mRNA of heat shock protein (HSP) genes,
      exemplified by Hsp17.6, Hsp18.2, and the two cytosolic ascorbate peroxidase genes
      Apx1, Apx2, reached similar levels by moderate heat stress (37 degrees C) or by
      treatment with H(2)O(2), butylperoxide and diamide at room temperature. The heat
      induced expression levels were significantly reduced in the presence of ascorbate
      or DPI indicating that H(2)O(2) is an essential component in the heat stress
      signalling pathway. Rapid (15 min) formation of heat shock promoter element (HSE)
      protein-binding complex of high molecular weight in extracts of heat-stressed or
      H(2)O(2)-treated cells and the inability to form this complex after ascorbate
      treatment suggests that oxidative stress affects gene expression via HSF
      activation and conversely, that H(2)O(2) is involved in HSF activation during the
      early phase of heat stress. The heat stress induction of a high mobility HSE
      binding complex, characteristic for later phase of heat shock response, was
      blocked by ascorbate and DPI. H(2)O(2 )was unable to induce this complex
      suggesting that H(2)O(2) is involved only in the early stages of HSF activation.
      Significant induction of the genes tested after diamid treatment and moderate
      expression of the sHSP genes in the presence of 50 mM ascorbate at 37 degrees C
      occurred without activation of HSF, indicating that other mechanisms may be
      involved in stress signalling.

PMID- 16897490
TI  - The auxin-induced K(+) channel gene Zmk1 in maize functions in coleoptile growth
      and is required for embryo development.
AB  - The transcript level and in turn protein density of the K(+)-uptake channel ZMK1
      in maize (Zea mays) coleoptiles is controlled by the phytohormone auxin. ZMK1 is
      involved in auxin-regulated coleoptile elongation as well as gravi- and
      phototropism. To provide unequivocal evidence for the role of ZMK1 in these
      elementary processes we screened for maize plants containing a Mutator-tagged
      Zmk1 gene. In a site-selected approach, we were able to identify three
      independent alleles of Mutator-transposon insertions in Zmk1. zmk1-m1::Mu1 plants
      were characterised by a Mu1 transposon inside intron 1 of ZMK1. When we analysed
      the Zmk1-transcript abundance in growing coleoptiles of these homozygous mutants,
      however, we found the K(+)-channel allele overexpressed. In consequence, elevated
      levels of K(+)-channel transcripts resulted in a growth phenotype as expected
      from more efficient K(+)-uptake, representing a central factor for turgor
      formation. Following Zmk1 expression during maize embryogenesis, we found this
      K(+)-channel gene constitutively expressed throughout embryo development and
      upregulated in late stages. In line with a vital role in embryogenesis, the
      mutations of exon 2 and intron 2 of Zmk1-zmk1-m2::Mu8 and zmk1-m3::MuA2-caused a
      lethal, defective-kernel phenotype. Thus, these results demonstrate the central
      role of the auxin-regulated K(+)-channel gene Zmk1 in coleoptile growth and
      embryo development.

PMID- 16897491
TI  - A single hemoglobin gene in Myrica gale retains both symbiotic and non-symbiotic
      specificity.
AB  - Here, a hemoglobin gene from the nitrogen-fixing actinorhizal plant Myrica gale
      was isolated, cloned and sequenced. The gene (MgHb) was a class I hemoglobin with
      strong sequence homology to non-symbiotic hemoglobin genes. MgHb is highly
      expressed in symbiotic root nodules, but transcripts and protein were also
      detected in leaves of M. gale. In Arabidopsis thaliana the MgHb promoter, linked
      to a beta-glucuronidase coding region, directed expression in the vascular
      tissue, in shoot meristem and at root branch point--a pattern very similar to the
      combined expression pattern of the two non-symbiotic A. thaliana hemoglobin
      promoters AHb1 and AHb2. The results points to a symbiotic as well as a non
      symbiotic specificity of MgHb similar to a hemoglobin gene identified in
      Parasponia andersonii, but different from the situation in Casuarina glauca--a
      close actinorhizal relative of M. gale.

PMID- 16897493
TI  - Visualizing bz1 missense suppression in Zea mays: an assay for monocot tRNA
      expression and utilization.
AB  - Bombardment of a highly expressed dicot tRNA(ala)(GAC) gene into Zea mays bz-E2
      or bz-E5 coleoptiles causes suppression of an Ala(458 )-->Val missense mutation,
      visualized by the development of anthocyanin pigment. Missense suppression is
      blocked by mutation of tRNA(ala)(GAC) at a site that prevents aminoacylation by
      the dicot alanyl-tRNA synthetase, indicating that features identified for
      expression and utilization of dicot tRNAs also function in monocots. This assay
      of the expression and utilization of tRNA(ala)(GAC) also can be used to study a
      variety of tRNAs and their genes, most of which can be relatively easily altered
      to be charged by alanyl tRNA synthetase.

PMID- 16897492
TI  - Floral patterning defects induced by Arabidopsis APETALA2 and microRNA172
      expression in Nicotiana benthamiana.
AB  - Floral patterning and morphogenesis are controlled by many transcription factors
      including floral homeotic proteins, by which floral organ identity is determined.
      Recent studies have uncovered widespread regulation of transcription factors by
      microRNAs (miRNAs), approximately 21-nucleotide non-coding RNAs that regulate
      protein-coding RNAs through transcript cleavage and/or translational inhibition.
      The regulation of the floral homeotic gene APETALA2 (AP2) by miR172 is crucial
      for normal Arabidopsis flower development and is likely to be conserved across
      plant species. Here we probe the activity of the AP2/miR172 regulatory circuit in
      a heterologous Solanaceae species, Nicotiana benthamiana. We generated transgenic
      N. benthamiana lines expressing Arabidopsis wild type AP2 (35S::AP2), miR172
      resistant AP2 mutant (35S::AP2m3) and MIR172a-1 (35S::MIR172) under the control
      of the cauliflower mosaic virus 35S promoter. 35S::AP2m3 plants accumulated high
      levels of AP2 mRNA and protein and exhibited floral patterning defects that
      included proliferation of numerous petals, stamens and carpels indicating loss of
      floral determinacy. On the other hand, nearly all 35S::AP2 plants accumulated
      barely detectable levels of AP2 mRNA or protein and were essentially non
      phenotypic. Overall, the data indicated that expression of the wild type
      Arabidopsis AP2 transgene was repressed at the mRNA level by an endogenous N.
      benthamiana miR172 homologue that could be detected using Arabidopsis miR172
      probe. Interestingly, 35S::MIR172 plants had sepal-to-petal transformations
      and/or more sepals and petals, suggesting interference with N. benthamiana normal
      floral homeotic gene function in perianth organs. Our studies uncover the
      potential utility of the Arabidopsis AP2/miR172 system as a tool for manipulation
      of floral architecture and flowering time in non-model plants.

PMID- 16897494
TI  - The 73 kD subunit of the cleavage and polyadenylation specificity factor (CPSF)
      complex affects reproductive development in Arabidopsis.
AB  - The cleavage and polyadenylation specificity factor (CPSF) is an important multi
      subunit component of the mRNA 3'-end processing apparatus in eukaryotes. The
      Arabidopsis genome contains five genes encoding CPSF homologues (AtCPSF160,
      AtCPSF100, AtCPSF73-I, AtCPSF73-II and AtCPSF30). These CPSF homologues interact
      with each other in a way that is analogous to the mammalian CPSF complex or their
      yeast counterparts, and also interact with the Arabidopsis poly(A) polymerase
      (PAP). There are two CPSF73 like proteins (AtCPSF73-I and AtCPSF73-II) that share
      homology with the 73 kD subunit of the mammalian CPSF complex. AtCPSF73-I appears
      to correspond to the functionally characterized mammalian CPSF73 and its yeast
      counterpart. AtCPSF73-II was identified as a novel protein with uncharacterized
      protein homologues in other multicellular organisms, but not in yeast. Both of
      the AtCPSF73 proteins are targeted in the nucleus and were found to interact with
      AtCPSF100. They are also essential since knockout or knockdown mutants are
      lethal. In addition, the expression level of AtCPSF73-I is critical for
      Arabidopsis development because overexpression of AtCPSF73-I is lethal.
      Interestingly, transgenic plants carrying an additional copy of the AtCPSF73-I
      gene, that is, the full-length cDNA under the control of its native promoter,
      appeared normal but were male sterile due to delayed anther dehiscence. In
      contrast, we previously demonstrated that a mutation in the AtCPSF73-II gene was
      detrimental to the genetic transmission of female gametes. Thus, two 73 kD
      subunits of the AtCPSF complex appear to have special functions during flower
      development. The important roles of mRNA 3'-end processing machinery in
      modulating plant development are discussed.

PMID- 16897495
TI  - Light-dependent polyploidy control by a CUE protein variant in Arabidopsis.
AB  - Endoreduplication is a special cell cycle that increases ploidy without cell and
      nuclear division. In plants endoreduplication is essential for development. We
      isolated a dominant Arabidopsis mutant from activation tagging lines that had
      increased polyploidy in darkness. This mutant, ipd1-1D (increased polyploidy
      level in darkness 1-1D), shows longer hypocotyls and increased ploidy levels only
      in dark-grown seedlings. The corresponding gene encodes a protein that contains a
      CUE domain variant. IPD1 is specifically expressed in mitotically dividing cells.
      Furthermore we show that blue and far-red light can suppress the ploidy increase
      in ipd1-1D and also suppress the reporter expression in IPD1-promoter beta
      glucuronidase transgenic plants. These results suggest that IPD1 regulates the
      endocycle leading to hypocotyl elongation and this function is controlled by blue
      and far-red light.

PMID- 16897496
TI  - Investigation of heavy metal contaminations in the lower Sakarya river water and
      sediments.
AB  - In this work, water and sediment samples were collected from three different
      stations located along the Sakarya river between May and September 2003. Lead,
      copper, chromium, zinc, nickel and cadmium concentrations were determined by
      using solvent extraction and flame atomic absorption spectrometric method. The
      results show that differences based upon sampling times, regions, sediment and
      water samples were observed. The mean levels of copper, nickel, chromium, lead,
      cadmium, zinc for sediment samples are; 4.630 microg g(-1), 13.520 microg g(-1),
      8.780 microg g(-1), 2.550 microg g(-1), 9.990 microg g(-1) and for water samples
      are; 0.851 microg g(-1), 1.050 microg g(-1), 0.027 microg g(-1), 1.786 microg g(
      1), 0.236 microg g(-1), 0.173 microg g(-1), respectively.

PMID- 16897497
TI  - Influence of environmental properties on macrobenthos in the northwest Indian
      shelf.
AB  - The paper deals with the standing stock of macrobenthic infauna and associated
      environmental factors influencing the benthic community in the shelf region of
      the northwest Indian coast. The data were collected onboard FORV Sagar Sampada
      during the winter monsoon (January-February, 2003) to understand the community
      structure and the factors influencing the benthic distribution. The environmental
      parameters, sediment characteristics and macrobenthic infauna were collected at
      26 stations distributed in the depths between 30 and 200 m extending from
      Mormugao to Porbander. Total benthic abundance was high in lower depths (50-75
      m), and low values noticed at 30 m depth contour was peculiar. Polychaetes were
      the dominant group and were more abundant in shallow and middle depths with
      moderate organic matter, clay and relatively high dissolved oxygen. On the other
      hand crustaceans and molluscs were more abundant in deeper areas having sandy
      sediment and low temperature. High richness and diversity of whole benthic groups
      observed in deeper depths counter balanced the opposite trend shown by polychaete
      species. Generally benthos preferred medium grain sized texture with low organic
      matter and high organic matter had an adverse effect especially on filter
      feeders. Deposit feeding polychaetes dominated in shallow depths while carnivore
      species in the middle depths. Ecologically, benthos were controlled by a
      combination of factors such as temperature, salinity, dissolved oxygen, sand and
      organic matter and no single factor could be considered as an ecological master
      factor.

PMID- 16897498
TI  - Determination of heavy metal pollution with environmental physicochemical
      parameters in waste water of Kocabas Stream (Biga, Canakkale, Turkey) by ICP-AES.
AB  - Waste water pollution of industrial areas can answer for the serious consequences
      of one of the most important environmental threats to the future. In this study,
      inductively coupled plasma-atomic emission spectrometry method (ICP-AES) is
      proposed to determine heavy metals (Pb, Cu, Cd, Cr, Zn, Al, Fe, Ni, Co, Mn) and
      major elements (Ca, Mg) in waste water of Kocabas Stream. The concentration of
      metals in the waste water samples taken from 9 different stations (St.) in Biga
      Kocabas Stream in November 2004 (autumn period) were determined after simple
      pretreatment of samples by the proposed ICP-AES method. An analysis of a given
      sample is completed in about 15 min for ICP-AES the method. The results of heavy
      metals concentrations in waste water were found between 0.00001-77.69610 mg l(-1)
      by the ICP-AES technique. The concentrations of Pb, Cd, Cu, Zn, Cr, Al, Fe, Mn,
      Ni, Co, Mg and Ca 0.00001 (St.3,6,7) - 0.0087 mg l(-1) (St.9), 0.00001 (St.4-7) -
      0.0020 mg l(-1) (St.8), 0.00001 (St.1,3-7,9) - 0.0041 mg l(-1) (St.2), 0.0620
      (St.2) - 0.2080 mg l(-1) (St.3), 0.0082 (St.6) - 0.2290 mg l(-1) (St.8), 0.3580
      (St.2) - 1.7400 mg l(-1) (St.3), 0.2240 (St.1) - 0.6790 mg l(-1) (St.3), 0.0080
      (St.1) - 1.5840 mg l(-1) (St.3), 0.0170 (St.3) - 0.0640 mg l(-1) (St.2), 0.0010
      (St.1,4,5,8) - 0.0080 mg l(-1) (St.3), 5.0640 (St.9) - 5.2140 mg l(-1) (St.1) and
      43.3600 (St.2) - 77.6961 mg l(-1) (St.9), respectively. Also we measured
      environmental physicochemical parameters such as temperature, salinity, specific
      conductivity, total dissolved solid (TDS), pH, oxidation and reduction potential
      (ORP), and dissolved oxygen (DO) in the waste water at sampling stations.

PMID- 16897500
TI  - Comparative salinity tolerance of three indigenous tropical freshwater cladoceran
      species; Moinodaphnia macleayi, Ceriodaphnia rigaudii and Diaphanosoma
      brachyurum.
AB  - The acute salinity tolerance of three tropical freshwater cladoceran species, M.
      macleayi, C. rigaudii and D. brachyurum was determined. The existence of these
      species represented new records for Trinidad and Tobago, a tropical Caribbean
      island. It has a large oil based industry, in which, the primary effluent (saline
      produced water) is discharged directly into many freshwater systems. Cladoceran
      species are used routinely in temperate regions, to assess the impacts of
      chemicals and effluents in freshwater systems. However, relatively few studies
      have assessed the salinity tolerance of these organisms. Test organisms were
      assayed using seven salinity treatments (0, 1, 3, 5, 10, 15, 20, 25 per thousand)
      prepared by volumetrically mixing natural filtered seawater with dilution water.
      C. rigaudii had a 48 h LC50 of 1.6 per thousand, M. macleayi 1.5 per thousand and
      D. brachyurum <1 per thousand. The CSmax (critical salinity maximum) for C.
      rigaudii and M. macleayi was 3 per thousand after 48 h, compared to 1 per
      thousand for D. brachyurum. There was no salinity value at which there was 100%
      survival. The resulting salinity response curve was a straight line which
      indicated that each species was intolerant of salt. Consequently, any of these
      can be considered as a representative freshwater organism for toxicity testing in
      Trinidad and Tobago.

PMID- 16897499
TI  - Variations and trends of ground-level ozone and AOT40 in the rural areas of
      Lithuania.
AB  - The analysis of data of the ground-level ozone concentration and accumulated
      ozone exposure over a threshold of 40 ppb (AOT40) in the rural areas of Lithuania
      is presented. Trends in the annual ozone mean, 95th and 25th percentiles were
      determined as statistically not significant at Preila and Rugsteliskes sites
      during the 1994-2004 period. Trends in the ozone concentration and its
      percentiles in the air masses arriving to Preila station in "polluted" and
      "unpolluted" sectors have been examined. Statistically significant changes in the
      ozone annual mean and 25th percentile were found in air masses in both "polluted"
      and "unpolluted" sectors in the 1988-2002 period. The trend analysis in the ozone
      monthly mean and percentiles for each month of the year revealed the main changes
      in the ozone level in both sectors during January-May. Insignificant downward
      trends in monthly 95th percentile in "unpolluted" sector and upward trends in
      "polluted" sector were found during summer months. Values of AOT40 for the
      protection of forests as well as crops and semi-natural vegetation were
      determined during the 1994-2004 period. The estimated AOT40 values for the
      protection of forests were lower than the critical level at Lithuanian rural
      sites but AOT40 values for the protection of crops and semi-natural vegetation
      were found to be higher than the critical level at both sites.

PMID- 16897501
TI  - Identifying potential receptors and routes of contaminant exposure in the
      traditional territory of the Ouje-Bougoumou Cree: land use and a geographical
      information system.
AB  - Great concern has been raised with respect to the 13 traplines that constitute
      the traditional territory of the Ouje-Bougoumou Cree located in the James Bay
      region of northern Quebec, Canada, with respect to mine wastes originating from
      three local mines. As a result, an "Integrative Risk Assessment" was initiated
      consisting of three interrelated components: a comprehensive human health study,
      an assessment of the existing ecological/environmental database, and a land
      use/potential sites of concern study. In this paper, we document past and present
      land use in the traditional territory of the Ouje-Bougoumou Cree for 72 heads of
      households, including 13 tallymen, and use a Geographic Information System (GIS)
      to layer harvest/hunting and gathering/collecting data over known mining areas
      and potential sites of concern. In this way, potential receptors of contamination
      and routes of human exposure were identified. Areas of overlap with respect to
      land use activity and mining operations were relatively extensive for certain
      harvesting activities (e.g., beaver, Castor canadensis and various species of
      game birds), less so for fish harvesting (all species) and water collection, and
      relatively restrictive for large mammal harvesting and collection of fire wood
      (and other collection activities). Potential receptors of contaminants associated
      with mining activity (e.g., fish and small mammals) and potential routes of
      exposure (e.g., ingestion of contaminated game and drinking of contaminated
      water) were identified.

PMID- 16897502
TI  - Influence of relative humidity and ozone on the sampling of volatile organic
      compounds on carbotrap/carbosieve adsorbents.
AB  - By using a dynamic dilution system, the atmospheric measurement of 11 selected
      toxics VOCs (ethylene, acetylene, propene, 1-butene, 1,3-butadiene, 1-pentene, 1
      hexene, benzene, toluene, ethylbenzene, m+p-xylene) from the list WHO of 1996 and
      TO-14 method of US EPA by preconcentration by thermal desorption (TD), analysis
      by gas chromatography (GC), identification and quantification with a flame
      ionisation detector (FID) was developed and validated in term of metrology,
      especially the techniques of sampling of these VOCs with adsorbents cartridges
      "Air Toxics" when used with an "UMEG sampler" equipped in the inlet with a nafion
      membrane. In particular the influence of climatic conditions (temperature and
      relative humidity) and the influence of chemical factors like ozone, on the
      representativity of sampling were studied. Experiments made with various
      humidities showed that the addition of a nafion membrane in the inlet of the
      sampling system was required. Without this membrane, losses of compounds were
      observed for RH >50%. With this membrane, storage for 2 weeks in a refrigerator,
      as for canisters, did not induce a loss of compounds. No significative decrease
      of concentrations of the studied VOCs after 14 days storage, which are known to
      react with ozone, were observed with an ozone concentrations of 55 ppb. One
      explanation is that nafion membrane, placed in the inlet of the sampler, will
      neutralize ozone before entering the sampling tubes. This observation is in
      accordance with literature which states that the sampling of VOCs on Carbotrap
      cartridges without ozone scrubber induce a loss of compounds.

PMID- 16897503
TI  - Inorganic constituents of urban air pollution in the Lazio region (Central
      Italy).
AB  - A field study was carried out at six locations in the Lazio region (Central
      Italy) aimed at characterising atmospheric particulate matter (PM10 and PM2.5)
      from the point of view of the chemical composition and grain size distribution of
      the particles, the mixing properties of the atmosphere, the frequency and
      relevance of natural events. The combination of four different analytical
      techniques (ion chromatography, X-ray fluorescence and ICP for inorganic
      components, thermo-optical analysis for carbon compounds) yielded sound results
      in terms of characterisation of the air masses. During the first three months of
      the study (October-December 2004), many pollution events of natural (sea-salt or
      desert dust episodes) or anthropogenic nature were identified and characterised.
      More than 90% of the collected mass was identified by chemical analysis. The
      central role played by the mixing properties of the lower atmosphere when
      pollution events occurred was highlighted. The results show a major impact of
      primary anthropogenic pollutants on traffic stations and a homogeneous
      distribution of secondary pollutants over the regional area. An evaluation of the
      sources of PM and an identification of possible reliable tracers were obtained
      using a chemical fractionation procedure.

PMID- 16897504
TI  - Adsorption and degradation of sulfosulfuron in soils.
AB  - Adsorption of sulfosulfuron was studied in two soils (topsoil from Alfisol and
      Inceptisol). The adsorption of sulfosulfuron was greater in topsoil collected
      from Alfisol than in Inceptisol. The soil sorption coefficient K and the soil
      organic carbon sorption coefficient K(oc) are the basic parameters used for
      describing the environmental fate of the herbicides. In topsoil the calculated K
      values from Alfisol was 4.43 and in topsoil from Inceptisol was 2.00. K(c) values
      were 6.06 in topsoil from Alfisol and 3.33 in topsoil from Inceptisol. The K(oc)
      values were 886.36 in topsoil from Alfisol and 770.26 in topsoil from Inceptisol.
      Field experimental plots with no previous history of sulfosulfuron were selected
      and studied the degradation of sulfosulfuron in the topsoil collected from
      Alfisol and Inceptisol. The half-life of sulfosulfuron in topsoil from Alfisol:
      T(1)- 3.97 days and T(2)- 4.54 days; topsoil from Inceptisol: T(1) - 4.68 days
      and T(2) - 5.52 days. The degradation of sulfosulfuron followed first-order
      kinetics. The persistence of sulfosulfuron was found relatively longer in the
      Inceptisol than in Alfisol. The combination of degradation data (t(1/2) - soil)
      and organic carbon based sorption (K(oc)) data of herbicides have been used to
      assess the pesticide environmental impact in soils through Gustafson Ubiquity
      Score (GUS). The GUS values were found to be 0.69 in topsoil from Alfisol and
      0.83 in Inceptisol.

PMID- 16897505
TI  - Morphological characterization of suspended particles under wind-induced
      disturbance in Taihu Lake, China.
AB  - Sediments are disturbed by wind frequently, especially in the shallow lakes. The
      characteristics of resuspended sediment particles in Taihu Lake were studied
      under different wind velocities. It showed that sediment particles suspended
      obviously and particle number in overlying water increased directly under high
      wind-induced disturbance. Suspended solid (SS) concentration was less than 50
      mg/l when the wind velocity was below 3.0 m/s, however, it increased to more than
      300 mg/l when the wind velocity was 10.0 m/s. Two methods were used to measure
      the fractal characteristics of particles. One was light scattering and the other
      was image analysis. The three-dimensional fractal dimensions of suspended
      particles, measured by light scattering, were between 2.26 and 2.44;
      correspondingly, the two-dimensional fractal dimensions, calculated by image
      analysis, were between 1.44 and 1.77. Moreover, the three-dimensional fractal
      dimensions were directly proportional to two-dimensional fractal dimensions. The
      characteristic length of particles was calculated by image analysis. The minimum
      characteristic length was close to 8.5 microm when the wind velocity was 1.5 m/s
      at 50 cm beneath lake surface, while, the maximum characteristic length was
      approximate to 24 microm when the wind velocity was 10 m/s at the depth of 150
      cm.

PMID- 16897506
TI  - The effect of temperature on PAHs emission from incineration of acrylic waste.
AB  - Incineration of acrylic waste solution in a lab scale quartz tube vertical
      incinerator showed the presence of 12-15 polycyclic aromatic hydrocarbons (PAHs)
      from a list of 16 priority pollutants at 700-1100 degrees C after an interval of
      50 degrees C. The amount of total 16 PAHs at 900 and 1100 degrees C was about 8.5
      and 1.25 times higher than those at 700 degrees C (739.48 microg g(-1))
      respectively. The amount of total probable (2A) and possible (2B) human
      carcinogenic PAHs was minimum at 700 degrees C.

PMID- 16897507
TI  - Development of simple and sensitive spectrophotometric method for the
      determination of bendiocarb in its formulations and environmental samples.
AB  - Facile, selective and sensitive spectrophotometric method has been developed for
      the determination of bendiocarb in its insecticidal formulations, fortified
      water, food grains, agriculture wastewater and agriculture soil samples with
      prepared reagents. The method was based on alkaline hydrolysis of the bendiocarb
      pesticide, and the resultant hydrolysis product of bendiocarb was coupled with
      2,6-dibromo-4-methylaniline to give a yellow color product with lambda max of 457
      nm or coupling with 2, 6-dibromo-4-nitroaniline to produce a red colored product
      with lambda max of 474 nm or coupling with 2, 4, 6-tribromoaniline to form orange
      red colored product has a lambda max of 465 nm. Under optimal conditions, Beer's
      law range for 2, 6-dibromo-4-methylaniline (DBMA) was found to be 0.6-14.0 microg
      mL (-1), 0.8-10.0 microg mL (-1) for 2, 6-dibromo-4-nitroaniline (DBNA) and 0.4
      10.0 microg mL (-1) for 2, 4, 6-tribromoaniline (TBA). The molar absorptivity of
      the color systems were found to be 4.126 x 10(4) l mol (-1) cm (-1) for DBMA,
      3.254 x 10(4) l mol (-1) cm (-1) for DBNA and 2.812 x 10(4) l mol (-1) cm (-1)
      for TBA. Sandell's of the color reactions are 0.018 microg cm (-2)(DBMA), 0.052
      microg cm (-2)(DBNA) and 0.065 microg cm (-2) (TBA) respectively. The effect of
      the non-target species on the determination of bendiocarb was studied. The
      formation of colored derivatives with the coupling agents is instantaneous and
      stable for 18 h, 30 h, and 12 h. Performance of the proposed methods were
      compared statistically in terms Student's F and t-tests with the reported
      methods.

PMID- 16897508
TI  - Coupling GIS and multivariate approaches to reference site selection for wadeable
      stream monitoring.
AB  - Geographic Information System (GIS) was used to identify potential reference
      sites for wadeable stream monitoring, and multivariate analyses were applied to
      test whether invertebrate communities reflected a priori spatial and stream type
      classifications. We identified potential reference sites in segments with
      unmodified vegetation cover adjacent to the stream and in >85% of the upstream
      catchment. We then used various landcover, amenity and environmental impact
      databases to eliminate sites that had potential anthropogenic influences upstream
      and that fell into a range of access classes. Each site identified by this
      process was coded by four dominant stream classes and seven zones, and 119
      candidate sites were randomly selected for follow-up assessment. This process
      yielded 16 sites conforming to reference site criteria using a conditional
      probabilistic design, and these were augmented by an additional 14 existing or
      special interest reference sites. Non-metric multidimensional scaling (NMS)
      analysis of percent abundance invertebrate data indicated significant differences
      in community composition among some of the zones and stream classes identified a
      priori providing qualified support for this framework in reference site
      selection. NMS analysis of a range standardised condition and diversity metrics
      derived from the invertebrate data indicated a core set of 26 closely related
      sites, and four outliers that were considered atypical of reference site
      conditions and subsequently dropped from the network. Use of GIS linked to stream
      typology, available spatial databases and aerial photography greatly enhanced the
      objectivity and efficiency of reference site selection. The multi-metric
      ordination approach reduced variability among stream types and bias associated
      with non-random site selection, and provided an effective way to identify
      representative reference sites.

PMID- 16897509
TI  - Environmental effects of dredging on sediment nutrients, carbon and granulometry
      in a tropical estuary.
AB  - This monitoring study encompassed a period prior to dredging, during dredging and
      post dredging between July 1999 to June 2000 in Ponggol estuary located along the
      northeastern coast of Singapore. Mean concentrations of sediment nutrients in mg
      x Kg(-1) (+/- standard error of means) prior to dredging, during dredging and
      post dredging were 9.75 +/- 4.24, 8.18 +/- 4.29 and 11.46 +/- 4.74 for ammonium,
      0.08 +/- 0.05, 0.06 +/- 0.02 and 0.09 +/- 0.01 for nitrite, 0.04 +/- 0.04, 0.11
      +/- 0.17 and 0.25 +/- 0.30 for nitrate, 4.83 +/- 3.48, 0.77 +/- 0.48 and 8.33 +/-
      9.73 for phosphate respectively. Pre dredge, dredge and post dredge levels of
      total carbon (TC) were 18.5 +/- 3.7, 20.2 +/- 3.5 and 34.6 +/- 12.0, of total
      organic carbon (TOC) were 10.5 +/- 2.9, 19.5 +/- 3.6 and 34.6 +/- 12.0 and of
      total inorganic carbon (TIC) were 7.9 +/- 1.0, 0.7 +/- 0.4 and non detectable in
      the sediments, respectively. Both, sediment nutrients and carbon registered lower
      concentrations with onset of dredging, with the exception of nitrate and TOC. A
      shift in sedimentary carbon from inorganic carbon to organic carbon was also
      observed with the onset of the dredging activities when the organically enriched
      historically contaminated layer was exposed. Sediment granulometry showed that
      the sediments in the estuary were predominantly silt and clay prior to dredging,
      which changed to sand with onset of dredging. Silt load in the sediments was
      highest post-dredge. Sediment nutrients and sediment organic carbon were observed
      to associate with the finer fractions (silt and clay) of sediments. Finer
      fractions of sediments get resuspended during a dredging event and are dispersed
      spatially as the result of tides and water movements. Prior to this study, the
      potential for nutrient release and sediment granulometry due to dredging have
      been suggested, but there have been few studies of it, especially in the tropics.
      The baseline information gathered from this study could be used to work out
      effective management strategies to protect similar tropical ecosystems elsewhere,
      should there be no other alternative to dredging.

PMID- 16897510
TI  - Chlorine emission during the chlorination of water--case study.
AB  - This paper deals with the incident of the excessive use of chlorine and leakage
      of unused chlorine from an industrial chlorination cistern and the lesson
      learned.

PMID- 16897511
TI  - Estimation of selenium concentration in shallow groundwater in alluvial fan area
      in Tsukui, Central Japan.
AB  - Total selenium (Se) and water-soluble Se in soil, and Se in a shallow groundwater
      were hydrogeochemically researched in an alluvial fan area in Tsukui, Central
      Japan. The water-soluble Se was estimated at average level of 2.6 +/- 1.2 microg
      Se kg(-1) dry soil (+/- SD, n = 25), showing less than 1% of the total Se (349
      508 microg Se kg(-1) dry soil) in soil. The monthly Se concentration in
      groundwater was average 2.2 microg,L(-1), ranging 1.6-2.4 microg,L(-1) during
      2001-2003. The Se in groundwater significantly decreased with increasing
      groundwater level after rainfall. This result indicated that Se-bearing water
      percolated with relatively low Se concentration through the soil layer. According
      to our prediction model of linear regression curve on the observation data, Se
      concentration in the groundwater was estimated to be increasing with the very low
      rate of 4.35 x 10(-3) microg Se L(-1),yr(-1). The hydrogeochemical research and
      the result of the prediction model showed that any explosive increase of Se will
      hardly occur in this groundwater without an anthropogenic Se contamination.

PMID- 16897512
TI  - Sources and distribution of trace metals in the Saricay Stream basin of
      southwestern Turkey.
AB  - Seasonal variation of the concentrations of trace metals (Cd, Co, Cr, Cu, Fe, Mn,
      Ni, Pb and Zn) were measured by ICP-AES in the water and sediment from the
      Saricay Stream, Geyik Dam and Ortakoy Well in the same basin. Comparisons between
      trace metal concentrations in water and sediment in three sources (Stream, Dam
      and Well) were made. The concentrations of a large number of trace metals in the
      water and sediment were generally higher in the Stream than in the Well and Dam,
      particularly in summer. Trace metal concentration ranges in sediments of the
      Saricay Stream and its sources showed very wide ranges (as mass ratio): Co: 5-476
      microg g(-1), Cr: 15-1308 microg g(-1), Cu: 7-128 microg g(-1), Fe: 1120-13210
      microg g(-1), Mn: 150-2613 microg g(-1), Ni: 102-390 microg g(-1), Pb: 0.7-31.3
      microg g(-1) and Zn: 18-304 microg g(-1), whereas Cd was not detected. Trace
      metal concentration ranges found in waters were: Co: 9.5-20.7 microg L(-1), Cr:
      20.3-284 microg L(-1), Cu: 170-840 microg L(-1), Fe: 176-1830 microg L(-1), Mn:
      29.3-387 microg L(-1), and Ni: 4.3-21.9 microg L(-1). Among the trace metals
      studied, Cd and Zn in two seasons and Pb in winter were usually not detected or
      in the recommended levels. In addition, Cd was not detected in the sediment
      during the winter season. The analysis of variance (one-way ANOVA) and
      correlation matrix was employed for the sediment and water samples of the two
      field surveys (summer and winter) comparison. The three sources showed
      differences in metal contents. The metal levels in sediments displayed marked
      seasonal and regional variations, which were attributed to anthropogenic
      influences and natural processes. In the Saricay Stream, high values of metals
      during the dry season showed an anthropological effect from small industry firms,
      e.g.: an olive mill and a dairy farm or water dilution during summer seasons.
      Finally, the pollution in this basin probably originated from small industrial,
      low quality coal-burned thermal power plants, and particularly agricultural and
      domestic waste discharges.

PMID- 16897513
TI  - Recovery of an estuary in the southwest coast of India from tsunami impacts.
AB  - Water quality in the Cochin Estuary, southwest coast of India during the tsunami
      attack was assessed and compared with the pre and post tsunami characteristics.
      From the results obtained, it is evident that a drastic change in hydrography has
      been inflicted by the energy transferred through the tsunami, which disturbed the
      entire estuarine embayment. However, the post tsunami water quality showed normal
      levels indicating that the region has recovered from the tsunami impacts.

PMID- 16897514
TI  - The landscape pattern characteristics of coastal wetlands in Jiaozhou Bay under
      the impact of human activities.
AB  - In this study, we interpreted coastal wetland types from an ASTER satellite image
      in 2002, and then compared the results with the land-use status of coastal
      wetlands in 1952 to determine the wetland loss and degradation around Jiaozhou
      Bay. Seven types of wetland landscape were classified, namely: shallow open
      water, inter-tidal flats, estuarine water, brackish marshes, salt ponds, fishery
      ponds and ports. Several landscape pattern indices were analysed: the results
      indicate that the coastal wetlands have been seriously degraded. More and more
      natural wetlands have been transformed into artificial wetlands, which covered
      about 33.7% of the total wetlands in 2002. In addition, we used a defined model
      to assess the impacts of human activities on coastal wetlands. The results
      obtained show that the coastal wetlands of Jiaozhou Bay have suffered severe
      human disturbance. Effective coastal management and control is therefore needed
      to solve the issues of the coastal wetland loss and degradation existing in this
      area.

PMID- 16897515
TI  - The relationships between certain physical and chemical variables and the
      seasonal dynamics of phytoplankton assemblages of two inlets of a shallow
      hypertrophic lake with different nutrient inputs.
AB  - The relationships between water discharge, temperature, total dissolved solids
      (TDS) conductivity, turbidity, nitrate, ammonium, phosphate and the seasonal
      dynamics of phytoplankton assemblages of two inlets of a shallow hypertrophic
      lake (Lake Manyas, Turkey) were studied between January 2003 and December 2004.
      The results showed that different levels of water discharge, turbidity,
      conductivity, TDS and nutrients could lead to the development of significantly
      different phytoplankton assemblages in inlets of shallow hypertrophic lakes. The
      multiple regression analysis identified water discharge, turbidity and water
      temperature as the driving factors behind the dynamics of phytoplankton biovolume
      in the studied inlets. The first two axes of Canonical Correspondence Analysis
      (CCA) explained 78% of the total variance in dominant phytoplankton species at
      Sigirci Inlet and 88% at Kocacay Inlet, respectively. The purpose of this study
      was to determine the relationships between water discharge, temperature,
      conductivity, turbidity, pH, TDS, nitrate, ammonium, phosphate and the seasonal
      dynamics of phytoplankton assemblages of two inlets of the shallow hypertrophic
      Lake Manyas, Turkey by means of multivariate statistical analysis.

PMID- 16897516
TI  - Assessment of thermal stratification within stream pools as a mechanism to
      provide refugia for native trout in hot, arid rangelands.
AB  - Native trout species, such as the redband trout (Oncorhynchus mykiss), occupy
      thermally harsh stream habitats in hot, arid rangeland basins of the western
      United States. Declines in the distribution and abundance of these species has
      generated interest in understanding how these cold water species survive in these
      systems, as well as in identifying opportunities to restore these species to
      their former ranges. The purpose of this study was to assess the potential for
      thermal stratification to provide thermal refuge for redband trout in stream
      pools characterized by warm intermittent flow conditions on arid rangelands. We
      studied vertical thermal stratification in two pools during three summers on
      Boles Creek located on the Modoc Plateau in extreme northeastern California.
      Water and air temperature data were collected on a 0.5 h time step from 15-Jun
      through 15-Sep during 1996, 1997, and 2000 using commercial temperature data
      loggers. Water temperature was measured at the top (0.3 m below pool surface) and
      bottom (0.3 m above pool substrates) of each pool. Vertical thermal
      stratification occurred within these pools creating conditions as much as 7.6 C
      cooler and consistently more constant at the bottom of pools compared to pool
      surface waters. Thermal stratification was dependent upon air temperature with
      the magnitude of stratification increasing as air temperature increased. The
      magnitude of thermal stratification varied significantly from year to year,
      likely reflecting variation in annual weather conditions. The thermal regime in
      the study pools was often near the upper lethal limit reported for redband trout,
      but temperatures at the bottom of these pools did offer refuge from lethal
      temperatures realized near the pool surface. Temperatures at pool bottom were
      consistently above optimal levels published for redbands.

PMID- 16897517
TI  - Distribution of ultraviolet solar radiation at Riyadh region, Saudi Arabia.
AB  - The ultraviolet UV solar radiation flux is monitored over a fixed time interval
      to study the daily, monthly and annual variations for a nearly one decade in
      Riyadh. Mathematical expressions will be presented based on a comparison between
      theoretical and experimental values. It is believed that the present analysis of
      UV radiation suggest that the environmental effects led to a better understanding
      of UV scattering, UV reflection, ozone and clouds layers in Riyadh and other
      selected areas in the mid-east region.

PMID- 16897518
TI  - Oxidative DNA damage levels and catalase activity in the clam Ruditapes
      decussatus as pollution biomarkers of Tunisian marine environment.
AB  - Levels of the oxidative DNA damage 7, 8-dihydro-8-oxo-2'-deoxyguanosine (8-oxodG)
      and catalase (CAT) activity were measured in the digestive gland and gills of
      clams Ruditapes decussatus, related to the presence of pollutants along Tunisian
      marine environment. Increased levels of CAT were observed in tissues of clams
      from all the sites studied, compared to control values, and elevated 8-oxodG
      levels were observed at specific sites. Results obtained in this work indicate
      that the measurement of 8-oxodG levels and CAT activity in tissues of R.
      decussatus is promising in pollution monitoring studies of the Tunisian marine
      environment.

PMID- 16897519
TI  - Water quality monitoring using remote sensing in support of the EU water
      framework directive (WFD): a case study in the Gulf of Finland.
AB  - Water quality monitoring using remote sensing has been studied in Finland for
      many years. But there are still few discussions on water quality monitoring using
      remote sensing technology in support of water policy and legislation in Finland
      under the WFD. In this study, we present water quality monitoring using remote
      sensing in the Gulf of Finland, and focus on the spatial distribution of water
      quality information from satellite-based observations in support of water policy
      by a case study of nitrate concentrations in surface waters. In addition, we
      briefly describe instruments using a system of river basin districts (RBD),
      highlighting the importance of integrated water resources and river-basin
      management in the WFD, and discuss the role of water quality monitoring using
      remote sensing in the implementation of water policy in Finland under the WFD.

PMID- 16897520
TI  - Biological integrity in mid-atlantic coastal plains headwater streams.
AB  - The objective of this study was to assess the applicability of using landscape
      variables in conjunction with water quality and benthic data to efficiently
      estimate stream condition of select headwater streams in the Mid-Atlantic Coastal
      Plains. Eighty-two streams with riffle sites were selected from eight-two
      independent watersheds across the region for sampling and analyses. Clustering of
      the watersheds by landscape resulted in three distinct groups (forest, crop, and
      urban) which coincided with watersheds dominant land cover or use. We used non
      parametric analyses to test differences in benthos and water chemistry between
      groups, and used regression analyses to evaluate responses of benthic communities
      to water chemistry within each of the landscape groups. We found that typical
      water chemistry measures associated with urban runoff such as specific
      conductance and dissolved chloride were significantly higher in the urban group.
      In the crop group, we found variables commonly associated with farming such as
      nutrients and pesticides significantly greater than in the other two groups.
      Regression analyses demonstrated that the numbers of tolerant and facultative
      macroinvertebrates increased significantly in forested watersheds with small
      shifts in pollutants, while in human use dominated watersheds the intolerant
      macroinvertebrates were more sensitive to shifts in chemicals present at lower
      concentrations. The results from this study suggest that landscape based
      clustering can be used to link upstream landscape characteristics, water
      chemistry and biotic integrity in order to assess stream condition and likely
      cause of degradation without the use of reference sites. Notice: Although this
      work was reviewed by EPA and approved for publication, it may not necessarily
      reflect official Agency policy.

PMID- 16897521
TI  - An innovative technique for lake management with reference to aeration unit
      installed at lower lake, Bhopal, India.
AB  - Water is key element in human life. All forms of life upon the earth depend upon
      water for their mere existence. Life & water may be aptly said to be two facets
      of the same coin. Most of the water bodies are getting polluted due to domestic
      waste, sewage, industrial waste and agricultural effluent. The present study is
      designed to ascertain the effectiveness of artificial aeration cum Ozonizer unit
      installed at Lower Lake, Bhopal for assessment of water quality. Various physico-
      chemical parameters like pH, Dissolved oxygen, Biochemical Oxygen demand,
      Chemical oxygen demand, nitrate, phosphate and bacteriological status were
      studied to assess the extent of deterioration in water quality of Lower lake and
      at the same time to assess the performance of the dual aeration system in
      improvement of water quality.

PMID- 16897522
TI  - Function approximation and documentation of sampling data using artificial neural
      networks.
AB  - Biodiversity studies in ecology often begin with the fitting and documentation of
      sampling data. This study is conducted to make function approximation on sampling
      data and to document the sampling information using artificial neural network
      algorithms, based on the invertebrate data sampled in the irrigated rice field.
      Three types of sampling data, i.e., the curve species richness vs. the sample
      size, the curve rarefaction, and the curve mean abundance of newly sampled
      species vs.the sample size, are fitted and documented using BP (Backpropagation)
      network and RBF (Radial Basis Function) network. As the comparisons, The
      Arrhenius model, and rarefaction model, and power function are tested for their
      ability to fit these data. The results show that the BP network and RBF network
      fit the data better than these models with smaller errors. BP network and RBF
      network can fit non-linear functions (sampling data) with specified accuracy and
      don't require mathematical assumptions. In addition to the interpolation, BP
      network is used to extrapolate the functions and the asymptote of the sampling
      data can be drawn. BP network cost a longer time to train the network and the
      results are always less stable compared to the RBF network. RBF network require
      more neurons to fit functions and generally it may not be used to extrapolate the
      functions. The mathematical function for sampling data can be exactly fitted
      using artificial neural network algorithms by adjusting the desired accuracy and
      maximum iterations. The total numbers of functional species of invertebrates in
      the tropical irrigated rice field are extrapolated as 140 to 149 using trained BP
      network, which are similar to the observed richness.

PMID- 16897523
TI  - Particulate matter over a seven year period in urban and rural areas within,
      proximal and far from mining and power station operations in Greece.
AB  - Lignite mining operations and lignite-fired power stations result in major
      particulate pollution (fly ash and fugitive dust) problems in the areas
      surrounding these activities. The problem is more complicated, especially, for
      urban areas located not far from these activities, due to additional contribution
      from the urban pollution sources. Knowledge of the distribution of airborne
      particulate matter into size fraction has become an increasing area of focus when
      examining the effects of particulate pollution. On the other hand, airborne
      particle concentration measurements are useful in order to assess the air
      pollution levels based on national and international air quality standards. These
      measurements are also necessary for developing air pollutants control strategies
      or for evaluating the effectiveness of these strategies, especially, for long
      periods. In this study an attempt is made in order to investigate the particle
      size distribution of fly ash and fugitive dust in a heavy industrialized (mining
      and power stations operations) area with complex terrain in the northwestern part
      of Greece. Parallel total suspended particulates (TSP) and particulate matter
      with an aerodynamic diameter less than 10 microm (PM10) concentrations are
      analyzed. These measurements gathered from thirteen monitoring stations located
      in the greater area of interest. Spatial, temporal variation and trend are
      analyzed over the last seven years. Furthermore, the geographical variation of
      PM10 - TSP correlation and PM10/TSP ratio are investigated and compared to those
      in the literature. The analysis has indicated that a complex system of sources
      and meteorological conditions modulate the particulate pollution of the examined
      area.

PMID- 16897524
TI  - Assessment of ambient air quality in urban centres of Haryana (India) in relation
      to different anthropogenic activities and health risks.
AB  - Considering the mounting evidences of the effects of air pollution on health, the
      present study was undertaken to assess the ambient air quality status in the fast
      growing urban centres of Haryana state, India. The samples were collected for
      total suspended particulate matter (TSPM), respirable suspended particulate
      matter (PM(10)), sulfur dioxide (SO(2)), and oxides of nitrogen (NO(2)) during
      different seasons from 8 districts of Haryana during January, 1999 to September,
      2000. The four types of sampling sites with different anthropogenic activities
      i.e. residential, sensitive, commercial and industrial were identified in each
      city. The ambient air concentration of TSPM and PM(10) observed was well above
      the prescribed standards at almost all the sites. The average ambient air
      concentrations of SO(2) and NO(2) were found below the permissible limits at all
      the centres. Comparatively higher concentration of SO(2) was observed during
      winter seasons, which seems to be related with the enhanced combustion of fuel
      for space heating and relatively stable atmospheric conditions. Air Quality Index
      (AQI) prepared for these cities shows that residential, sensitive and commercial
      areas were moderately to severely polluted which is a cause of concern for the
      residents of these cities. The high levels of TSPM and SO(2) especially in winter
      are of major health concern because of their synergistic action. The data from
      Hisar city reveals a significant increase in the total number of hospital
      visits/admissions of the patients with acute respiratory diseases during winter
      season when the level of air pollutants was high.

PMID- 16897525
TI  - Patterns of spatial autocorrelation in stream water chemistry.
AB  - Geostatistical models are typically based on symmetric straight-line distance,
      which fails to represent the spatial configuration, connectivity, directionality,
      and relative position of sites in a stream network. Freshwater ecologists have
      explored spatial patterns in stream networks using hydrologic distance measures
      and new geostatistical methodologies have recently been developed that enable
      directional hydrologic distance measures to be considered. The purpose of this
      study was to quantify patterns of spatial correlation in stream water chemistry
      using three distance measures: straight-line distance, symmetric hydrologic
      distance, and weighted asymmetric hydrologic distance. We used a dataset
      collected in Maryland, USA to develop both general linear models and
      geostatistical models (based on the three distance measures) for acid
      neutralizing capacity, conductivity, pH, nitrate, sulfate, temperature, dissolved
      oxygen, and dissolved organic carbon. The spatial AICC methodology allowed us to
      fit the autocorrelation and covariate parameters simultaneously and to select the
      model with the most support in the data. We used the universal kriging algorithm
      to generate geostatistical model predictions. We found that spatial correlation
      exists in stream chemistry data at a relatively coarse scale and that
      geostatistical models consistently improved the accuracy of model predictions.
      More than one distance measure performed well for most chemical response
      variables, but straight-line distance appears to be the most suitable distance
      measure for regional geostatistical modeling. It may be necessary to develop new
      survey designs that more fully capture spatial correlation at a variety of scales
      to improve the use of weighted asymmetric hydrologic distance measures in
      regional geostatistical models.

PMID- 16897526
TI  - Potential use of the plant antioxidant network for environmental exposure
      assessment of heavy metals in soils.
AB  - In recent years, awareness has risen that the total soil content of pollutants by
      itself does not suffice to fully assess the potential ecotoxicological risks
      involved. Chemical analysis will require to be complemented with biological
      assays in a multidisciplinary approach towards site specific ecological risk
      assessment (SS-ERA). This paper evaluates the potential use of the plants'
      antioxidant response to metal-induced oxidative stress to provide a sensitive
      biological assay in SS-ERA. To this end, plants of Phaseolus vulgaris were grown
      for two weeks on 15 soils varying in contamination level. Morphological
      parameters and enzymatic plant responses were measured upon harvest. Foliar
      concentrations of the (heavy) metals Al, Cu, Cd, Cr, Fe, Mn, Ni, Pb, Zn were also
      determined. Metal mobility in the soil was further assessed by determining soil
      solution and NH4OAc extractable levels. In general more significant correlations
      were observed between plant responses and foliar metal concentrations or
      exchangeable/soluble levels than between plant responses and the total soil
      content. The study demonstrates the potential use of the plants' antioxidant
      defence mechanisms to assess substrate phytotoxicity for application in SS-ERA
      protocols. However, the system, based on calculation of a soil Phytotoxicity
      Index (PI), will require adaptation and fine-tuning to meet the specific needs
      for this type of environmental monitoring. Large variation was observed in
      phytotoxicity classification based on the various test parameters. The thresholds
      for classification of the various morphological and enzymatic response parameters
      may require adaptation according to parameter stress sensitivity in order to
      decrease the observed variation. The use of partial PI's (leaves and roots
      separately) may in addition increase the sensitivity of the system since some
      metals show specific effects in one of both organs only. Loss of biological
      functionality of enzymes, as was observed for ICDH in one of the more strongly
      contaminated soils, may also be recognized as an additional stress symptom when
      assigning phytotoxicity classification, whereas the current system only considers
      increasing enzymatic capacities. Other easily distinguishable parameters, which
      could be added to the current indexation are: failure to germinate and the
      incapacity to develop roots in the toxic substrate. Additional research will be
      required to determine the possible application range of soil properties for this
      biological assay and to further improve its performance in SS-ERA.

PMID- 16897527
TI  - Heavy metal load of soil, water and vegetables in peri-urban Delhi.
AB  - Peri-urban lands are often used for production of vegetables for better market
      accessibility and higher prices. But most of these lands are contaminated with
      heavy metals through industrial effluents, sewage and sludge, and vehicular
      emission. Vegetables grown in such lands, therefore, are likely to be
      contaminated with heavy metals and unsafe for consumption. Samples of vegetables
      i.e., spinach (Spinacia oleracea L.) and okra (Abelmoschus esculentus L.); soil
      and irrigation water were collected from 5 peri-urban sites of New Delhi to
      monitor their heavy metal loads. While heavy metal load of the soils were below
      the maximum allowable limit prescribed by the World Health Organization (WHO), it
      was higher in irrigation water and vegetable samples. The spinach and okra
      samples showed Zn, Pb and Cd levels higher than the WHO limits. The levels of Cu,
      however, were at their safe limits. Metal contamination was higher in spinach
      than in okra. Spatial variability of metal contamination was also observed in the
      study. Bio-availability of metals present in soil showed a positive relationship
      with their total content and organic matter content of soil but no relationship
      was observed with soil pH. Washing of vegetables with clean water was a very
      effective and easy way of decontaminating the metal pollution as it reduced the
      contamination by 75 to 100%.

PMID- 16897528
TI  - Flow-specific trends in river-water quality resulting from the effects of the
      Clean Air Act in three mesoscale, forested river basins in the northeastern
      United States through 2002.
AB  - Two new methods for assessing temporal trends in stream-solute concentrations at
      specific streamflow ranges were applied to long (40 to 50-year) but sparse (bi
      weekly to quarterly sampling) stream-water quality data collected at three
      forested mesoscale basins along an atmospheric deposition gradient in the
      northeastern United States (one in north-central Pennsylvania, one in
      southeastern New York, and one in eastern Maine). The three data sets span the
      period since the implementation of the Clean Air Act in 1970 and its subsequent
      amendments. Declining sulfate (O4(2-)) trends since the mid 1960s were identified
      for all 3 rivers by one or more of the 4 methods of trend detection used. Flow
      specific trends were assessed by segmenting the data sets into 3-year and 6-year
      blocks, then determining concentration-discharge relationships for each block.
      Declining sulfate (O4(2-)) trends at median flow were similar to trends
      determined using a Seasonal Kendall Tau test and Sen slope estimator. The trend
      of declining O4(2-) concentrations differed at high, median and low flow since
      the mid 1980s at YWC and NR, and at high and low flow at WR, but the trends
      leveled or reversed at high flow from 1999 through 2002. Trends for the period of
      record at high flows were similar to medium- and low-flow trends for Ca2++ Mg2+
      concentrations at WR, non-significant at YWC, and were more negative at low flow
      than at high flow at NR; trends in nitrate (NO3-), and alkalinity (ALK)
      concentrations were different at different flow conditions, and in ways that are
      consistent with the hydrology and deposition history at each watershed. Quarterly
      sampling is adequate for assessing average-flow trends in the chemical parameters
      assessed over long time periods (approximately decades). However, with even a
      modest effort at sampling a range of flow conditions within each year, trends at
      specified flows for constituents with strong concentration-discharge
      relationships can be evaluated and may allow early detection of ecosystem
      response to climate change and pollution management strategies.

PMID- 16897529
TI  - The characteristics of tropospheric ozone seasonality observed from ozone
      soundings at Pohang, Korea.
AB  - This paper presents the first analysis of vertical ozone sounding measurements
      over Pohang, Korea. The main focus is to analyze the seasonal variation of
      vertical ozone profiles and determine the mechanisms controlling ozone
      seasonality. The maxima ozone at the surface and in the free troposphere are
      observed in May and June, respectively. In comparison with the ozone seasonality
      at Oki (near sea level) and Happo (altitude of 1840 m) in Japan, which are
      located at the same latitude as of Pohang, we have found that the time of the
      ozone maximum at the Japanese sites is always a month earlier than at Pohang.
      Analysis of the wind flow at the surface shows that the wind shifts from westerly
      to southerly in May over Japan, but in June over Pohang. However, this wind shift
      above boundary layer occurs a month later. This wind shift results in
      significantly smaller amounts of ozone because the southerly wind brings clean
      wet tropical air. It has been suggested that the spring ozone maximum in the
      lower troposphere is due to polluted air transported from China. However, an
      enhanced ozone amount over the free troposphere in June appears to have a
      different origin. A tongue-like structure in the time-height cross-section of
      ozone concentrations, which starts from the stratosphere and extends to the
      middle troposphere, suggests that the ozone enhancement occurs due to a gradual
      migration of ozone from the stratosphere. The high frequency of dry air with
      elevated ozone concentrations in the upper troposphere in June suggests that the
      air is transported from the stratosphere. HYSPLIT trajectory analysis supports
      the hypothesis that enhanced ozone in the free troposphere is not likely due to
      transport from sources of anthropogenic activity.

PMID- 16897530
TI  - Suggested guidelines for use of avian species as biomonitors.
AB  - An animal's suitability as a biomonitor of environmental change can be determined
      by biological, reproductive and ecological characteristics determined at the
      class, order and species level. The animal's habitat where the research is to be
      performed and the form, function and structure of the environmental change being
      studied within that habitat also determines suitability. Non-threatened
      populations of large, non-migratory, long-lived, seasonally-breeding tertiary
      avian predators, whose dietary preferences are narrow and known, can be useful as
      monitors of environmental chemical contaminants. If chemicals are being
      monitored, a quantifiable endpoint effect must be demonstrated in the species, or
      a similar species under experimental laboratory conditions. Logistical and
      economic issues as well as public and regulatory authority acceptance should also
      be considered when assessing the suitability of a species as a biomonitor.

PMID- 16897531
TI  - Faecal coliform bacteria in Febros river (northwest Portugal): temporal
      variation, correlation with water parameters, and species identification.
AB  - Febros river water was sampled weekly, during 35 successive weeks, and analyzed
      for microbiological (total coliforms, faecal coliforms, faecal streptococci and
      enterococci) and chemical-physical (ammonia and temperature) parameters. All
      microbiological parameters were highly correlated with each other and with
      ammonia, suggesting that the simultaneous determination of all variables
      currently in use in the evaluation of the microbiological quality of waters is
      probably redundant, and could be simplified, and that ammonia should be tested as
      a sentinel parameter of the microbiological pollution load of Febros river. From
      the strains isolated from positive tubes of the faecal coliforms test (multiple
      tube fermentation technique) and retested in this assay, Escherichia coli,
      Klebsiella oxytoca and Klebsiella pneumoniae subsp. pneumoniae strains were
      positive, indicating that the faecal coliforms test is not totally specific for
      Escherichia coli, and can detect other bacteria. Considering that these
      Klebsiella spp. are not necessarily of faecal origin, it was concluded that the
      faecal coliforms test can overestimate true faecal pollution. From the strains
      isolated from positive tubes of the faecal coliforms procedure, only Escherichia
      coli strains were clearly positive in the beta-D-glucuronidase test. All other
      species were negative or very weakly positive, suggesting that the assay of the
      beta-D-glucuronidase activity is less prone to false positives than the faecal
      coliforms test in the quantification of Escherichia coli in environmental waters.

PMID- 16897532
TI  - Cancer and non-cancer health risk from eating cassava grown in some mining
      communities in Ghana.
AB  - Food crops such as cassava, cocoyam and other tuber crops grown in mining
      communities uptake toxic or hazardous chemicals such as arsenic, and cadmium,
      from the soil. Cassava is a stable food for Ghanaians. This study evaluated human
      health risk from eating cassava grown in some mining communities in Ghana such as
      Bogoso, Prestea, Tarkwa and Tamso, which are important mining towns in the
      Western Region of Ghana. The study evaluated cancer and non-cancer health effects
      from eating cassava grown in the study areas in accordance with US Environmental
      Protection Agency's Risk Assessment guidelines. The results of the study revealed
      the following: cancer health risk for Tamso, 0.098 (RME--Reasonable Maximum
      Exposure) and 0.082 (CTE--Central Tendency Exposure). This means that
      approximately 10 and 8 out of 100 resident adults are likely to suffer from
      cancer related cases by RME and CTE parameters respectively. For Prestea, we have
      0.010 and 0.12, which also means that approximately 1 out of 100 and 10 resident
      adults out of 100 are also likely to suffer from cancer related diseases by RME
      and CTE parameters. The results of the study obtained were found to be above the
      acceptable cancer risk range of 1x 10(-6) to 1x 10(-4), i.e., 1 case of cancer
      out of 1 million or 100,000 people respectively.

PMID- 16897533
TI  - Non-cancer health risk assessment from exposure to cyanide by resident adults
      from the mining operations of Bogoso Gold Limited in Ghana.
AB  - Cyanide is a very toxic chemical that is used to extract gold from its ores.
      Wastewaters from gold mining companies such as Bogoso Gold Limited (BGL) contain
      cyanide and other potentially toxic chemicals that have adverse effects on human
      beings and aquatic organisms. This study was conducted to evaluate the human
      health risk assessment from exposure to free cyanide via oral and dermal contact
      of surface/underground water by resident adults within the concession of Bogoso
      Gold Limited. The chronic non-cancer health risk from exposure to cyanide in
      River Bogo Upstream is 230 and 43 (by Central Tendency Exposure (CTE) parameters
      respectively). This means that approximately 230 and 43 resident adults are
      likely to suffer diseases related to cyanide intoxication via oral and dermal
      contact respectively. For chronic exposure to River Bogo Downstream by resident
      adults, the non-cancer health risks are: 0.031 and 0.57 via oral and dermal
      contact for CTE parameters respectively, which also means that, the non-cancer
      health risks associated with cyanide intoxication is negligible as the hazard
      index is less than 1.0 via oral and dermal contacts respectively. The results
      showed that health risk for acute exposure to cyanide by the resident adults is
      very high. Hence the residents attribute most of the unexplained deaths in the
      communities to accidental ingestion and dermal contact of cyanide water.

PMID- 16897534
TI  - Bioaccumulation of some heavy metals in different tissues of Dicentrarchus labrax
      L, 1758, Sparus aurata L, 1758 and Mugil cephalus L, 1758 from the Camlik lagoon
      of the eastern coast of Mediterranean (Turkey).
AB  - In this study, bioaccumulation of the heavy metals (Fe, Zn, Cd) in the liver,
      gill, gonad and muscle tissues of Dicentrarchus labrax, Mugil cephalus and Sparus
      aurata were investigated seasonally. Camlik is the important fisheries lagoon
      located in The Iskenderun Bay, Mediterranean coast of Turkey. Due to heavy
      industrial and agricultural activities in the region, the bay has the polluted
      coastal waters of Turkey. Therefore, the levels of cadmium, zinc, iron were
      determined in the muscle in each species because of its importance for human
      consumption and also the liver, gill, gonad were analysed since these organs tend
      to accumulate metals. Heavy metal levels were found generally higher in the liver
      and gill than the gonad and muscle tissues in three species; the levels of all
      metals in a given tissue were generally higher in Mugil cephalus than the other
      two species. Data collected in this study suggest that Camlik lagoon is affected
      by a relatively metal pollution. The concentrations of Zn concentrations in the
      muscle tissues exceeded the acceptable levels for a food source for human
      consumption and other metals in the edible parts of the investigated fish were in
      the permissible safety levels for human uses.

PMID- 16897535
TI  - A characterization of selected endocrine disruptor compounds in a Portuguese
      wastewater treatment plant.
AB  - Anthropogenic compounds that are able to disrupt the endocrine system of wildlife
      species are a major cause for concern and have led to a demand for new screening
      methods. The identification and quantification of endocrine disruptor compounds
      at wastewater treatment plant is of major interest to assess the endocrine
      activity of wastewater treatment plant discharges into the environment. This
      study consists of a preliminary survey of concentrations of previously selected
      endocrine disruptor compounds, undertaken to establish environmental
      concentrations and to support a biological program assay exposing freshwater fish
      to them. Selected endocrine disrupting chemicals (APEs, bisphenol A and 17 beta
      estradiol) were measured in samples from a wastewater treatment plant located in
      Lisbon (Portugal), using recent commercial enzyme-linked immunosorbent assay kits
      and also LC-MS/MS. The results show that the wastewater treatment plant treatment
      process is efficient on the removal of target endocrine disruptor compounds.
      However, environmentally significant concentrations are still present in the
      treated effluent. The results also show that enzyme-linked immunosorbent assay
      kit is suitable for routine analysis of the selected compounds. The results are
      also useful since the wastewater treatment plant is located in a Mediterranean
      region, which results in an effluent with its own characteristics.

PMID- 16897536
TI  - Distribution and statistical analysis of leachable and total heavy metals in the
      sediments of the Suez Gulf.
AB  - The concentrations of nine heavy metals (Cd, Co, Cr, Cu, Fe, Mn, Ni, Pd and Zn)
      in the labile and total fractions of muddy and sandy sediment samples collected
      from twelve sites in Suez Gulf during April 1999 were studied to evaluate the
      pollution status of the Suez Gulf. The enrichment factors (EF) for each element
      were calculated. There are extremely high concentrations of Cd, Ni, Pb and
      slightly concentration of Cr and Cu in both muddy and sandy sediments. The
      concentration of Zn was moderately high and can be considered as seriously
      contaminate Metal pollution index (MPI) shows high values ranged between 46 to
      156 and 40 to 232 for both sandy and muddy sediments, respectively.
      Concentrations of heavy metals were normalized against iron for total fraction in
      both of sandy and muddy sediments. Principal component analysis (PCA) was studied
      on the data matrix obtained and represented three-factor model explaining 92.22%
      for labile and 88.82% for total fractions of muddy sediment. The main source of
      contamination is the offshore oil fields and industrial wastes. This is largely a
      result of ineffective and inefficient operation equipment, illegal discharge of
      dirty ballast water from tankers and lack of supervision and prosecution of
      offenders.

PMID- 16897537
TI  - Effects of flooding on lead and cadmium speciation in sediments from a drinking
      water reservoir.
AB  - Rimov water reservoir on the river Malse is the main source of drinking water for
      the town of Ceske Budejovice and for the majority of inhabitants in the South
      Bohemian region, Czech Republic. Changes in cadmium and lead contents in bottom
      sediments before and after an extensive flood on the river Malse in August, 2002
      were therefore determined. A five-step sequential extraction procedure was used
      in order to obtain more detailed information about the influence of the flood on
      heavy metal retention. In order to determine the mobility of lead and cadmium,
      the mobility factor (MF) for these heavy metals was calculated. The mobility
      factor of cadmium showed a significant decrease in the upper parts of the
      sediment profiles after the flood (e.g., from 59.4% to 49.1%) caused by a release
      of cadmium especially from the exchangeable fraction. There were no significant
      changes in the lead mobility factor after the flood, but a decrease of lead
      concentration in the exchangeable fraction was observed. Presented results show
      that the flood led to a leaching of the heavy metals present in bottom sediments
      into the environment.

PMID- 16897538
TI  - Development of a grassland integrity index based on breeding bird assemblages.
AB  - We utilized landscape and breeding bird assemblage data from three Breeding Bird
      Survey (BBS) routes sampled from 1965-1995 to develop and test a grassland
      integrity index (GII) in a mixed-grass prairie area of Oklahoma. The overall
      study region is extensively fragmented from long-term agricultural activity, and
      native habitat remnants have been degraded by recent encroachment of woody
      vegetation, namely eastern red cedar (Juniperus virginiana L.). The 50 individual
      bird survey points along the BBS routes, known as stops, were used as sample
      sites. Our process first focused on developing a grassland disturbance index
      (GDI) as a measure of cumulative landscape disturbances for these sites. The GDI
      was based on five key landscape variables identified in an earlier species-level
      study of long-term avian community dynamics: total tree, shrub, and herbaceous
      vegetation cover indices, overall mean landscape patch size, and grassland patch
      core size. The GII was then developed based on breeding bird assemblage data.
      Assemblages were based on commonly used response guilds reflective of five avian
      life history parameters: foraging mode/location, nesting location, habitat
      specificity, migratory pattern, and dietary guild. We tested the response of 78
      candidate assemblage metrics to the GDI, and eliminated those with no or poor
      response or with high correlations (redundant), resulting in 13 metrics for use
      in the final index. Individual metric scores were scaled to fall between 0 and
      10, and the cumulative index to range from 0 to 100. Although broader application
      and refinement are possible, the avian-based GII has an advantage over labor
      intensive, habitat-based monitoring in that the GII is derived from readily
      available long-term BBS data. Therefore, the GII shows promise as an inexpensive
      tool that could easily be applied over other areas to monitor changes in regional
      grassland conditions.

PMID- 16897539
TI  - Patchy distribution fields: sampling distance unit of an interleaved survey and
      reconstruction adequacy.
AB  - A mathematical model was used to examine the effects of choosing various units of
      sampling distance of an interleaved (two-pass) acoustic survey on the adequacy of
      reconstructing patchy distribution fields. The model simulates fish or plankton
      patches (or gaps) of different shapes and spatial orientations, and an
      interleaved survey by parallel or zigzag transects, along which a unit of
      sampling distance is set. The efficiency of a survey is determined by the
      adequacy of a reconstructed field to that originally generated, which is
      evaluated by calculating their correlations (r). Regarding immovable fields, the
      experiments conducted indicate that a patchy field can be reconstructed properly
      (r2 > 0.70) if the distance between transects D < (1.5-2.0)R and the unit of
      sampling distance d < (1.5- 2.0)R(p). As, for regular surveys d < (1.0-1.5)R(p),
      it may be concluded that interleaved surveys are more efficient than regular ones
      because of the factor studied. In regard to movable fields, a comparison of the
      results of interleaved surveys with those of regular surveys directly indicates
      that the former may ensure a more adequate field reconstruction than the latter
      do. This fact confirms the previous conclusion that an interleaved survey is
      expedient in cases where there is no preference regarding the position of a
      vessel for further work.

PMID- 16897540
TI  - Factors affecting participating farmers' willingness-to-pay for the Tree Farming
      Fund: a study in a participatory forest in Bangladesh.
AB  - This paper examined the factors that might influence participating farmers'
      willingness-to-pay for the Tree Farming Fund (TFF) established for sustainable
      development of participatory forest management (PFM). Information on willingness
      to-pay, socioeconomic characteristics, and attitudes of participating farmers
      toward TFF were obtained from interviews with 581 participating farmers. Logistic
      regression analysis was used to determine the dominant factors that might
      influence participating farmers' willingness-to-pay for the TFF. The results
      showed that participating farmers' willingness-to-pay was significantly affected
      by (i) family income; (ii) education level; (iii) confidence that his aspired
      benefits will be received; (iv) agreement with the statement that 'PFM is
      sustainable under the present state of management'; (v) agreement with the
      statement that 'PFM is a good strategy for forest conservation'; and (vi)
      knowledge of PFM strategies. Thus, participating farmers with a higher level of
      education, higher income and positive attitudes toward TFF tended to express more
      willingness-to-pay. Establishment of TFF could be an effective strategy in
      implementing sustainable PFM in Bangladesh. For this strategy to succeed,
      however, active partnership between the participating farmers and Forest
      Department is required. Participating farmers' attitudes toward TFF should
      therefore be taken into consideration as should the results of this study, which
      are important indicators of participating farmers' positive attitudes toward TFF.

PMID- 16897542
TI  - Measurements of wastewater true color by 4/6 wavelength methods and artificial
      neural network.
AB  - The ADMI (American Dye Manufactures' Institute) 3 and 31 wavelength (WL) methods
      are the most popular measurements of the wastewater true color. However,
      significantly different measured results were found between the ADMI 3 and 31 WL
      methods for the same sample. This finding indicates that the ADMI 3 and 31 WL
      values should not be directly substituted for each other, resulting in the
      incomparability of these two color values. An innovative calculation using the
      Back-Propagation Neural Network (BPN) was therefore proposed to replace the
      original calculation method proposed in Standard Method. The BPN-calculated ADMI
      3 WL values were found to be very close to the corresponding measured ADMI 31 WL
      values. Additionally, for more accurate measurement of the true color, new
      measurement methods containing 4 and 6 wavelengths were proposed and cooperated
      with the BPN calculation model. The new approaches performed very accuracy
      measured results of the wastewater true color. Finally, the trained BPN
      calculation models were built to be applied to measure the true color of real
      textile samples and also performed very good measured results.

PMID- 16897541
TI  - Simple model of dissolved oxygen consumption in a bay within high organic
      loading: an applied remediation tool.
AB  - San Vicente Bay is a coastal shallow embayment in Central Chile with multiple
      uses, one of which is receiving wastewater from industrial fisheries, steel mill
      effluents, and domestic sewage. A simulation model was developed and applied to
      dissolved oxygen consumption by organic residues released into this embayment.
      Three compartments were established as function of: depth, circulation and
      outfall location. The model compartments had different volumes, and their oxygen
      saturation value was used as baseline. The parameters: (a) BOD5 of the industrial
      and urban effluents, (b) oxygen demand by organic sediments, (c) respiration, (d)
      photosynthesis and (e) re-aeration were included in the model. Iteration results
      of the model showed severe alterations in Compartment 1, with a decrease of 65%
      in the oxygen below saturation. Compartment 2 showed a small decline (10%) and
      compartment 3 did not show apparent changes in oxygen values. Measures
      recommended for remediation were to decrease the BOD5 loading by 30% in the
      affected sector. Iteration of the model for 200 h following recommendations
      derived from the preceding results produced an increase in saturation of 60% (5
      ml O2 L(-1)), which suggested an improvement of the environmental conditions.

PMID- 16897543
TI  - Distribution, enrichment and accumulation of heavy metals in coastal sediments of
      Salina Cruz Bay, mexico.
AB  - Surface sediment samples collected from the Salina Cruz Bay in the last twenty
      years, were analyzed for the total available trace elements (Cr, Cu, Fe, Pb, Ni,
      V, and Zn) to evaluate metal contamination due to possible anthropogenic inputs.
      Normalization of metals to iron and fine-grained fraction (< 63 microm) indicated
      relatively high enrichment factors for lead during the last two decades. Sediment
      Quality Guidelines suggest that lead must be considered as a chemical of
      potential concern in the marine and estuarine ecosystem. Concentration levels of
      lead ranged from 5-124 microg/g, while Ni and V below 70 and 30 microg/g,
      respectively. Geoaccumulation and enrichment factors for the rest of elements
      show comparable values to those reported for sites with similar activities in the
      world. Spatial distribution suggests that in addition to harbor activities, a
      transboundary source for Pb must account for the observed trends.

PMID- 16897544
TI  - Microtrace metalloids speciation in lakes water samples (Poland).
AB  - This paper presents the results of the determination of arsenic, antimony and
      selenium concentrations of inorganic speciation in surface water samples from
      Gniezno city (western Poland) and its neighborhood. The concentration of elements
      were up to 1.85 ng/ml for arsenic, 1.61 ng/ml for antimony and 0.45 ng/ml for
      selenium (detection limits: 0.04 ng/ml for As and Sb and 0.03 ng/ml for Se). A
      variety of concentrations for the determined elements has been obtained in waters
      from Gniezno city's neighborhood and in water from down-town reservoirs which are
      under strong anthropogenic pressure.

PMID- 16897545
TI  - Trace element concentrations and bioindicator responses in tree swallows from
      northwestern Minnesota.
AB  - Extremely high concentrations of cadmium (3.5 microg/g dry wgt.) and elevated
      concentrations of chromium (>10 microg/g dry wgt.) and mercury (1.6 microg/g dry
      wgt.) were reported in waterbird tissues at Agassiz National Wildlife Refuge in
      northwestern Minnesota in 1994. Tree swallows (Tachycineta bicolor) were studied
      during 1998-2001 at three drainages into the Refuge, two pools on the Refuge, and
      at a nearby reference location to document whether high levels of contaminants
      were still present, and if so to quantify the source and severity of the
      contamination. Trace elements were measured in tree swallow eggs, livers, and
      diet. Reproductive success and bioindicator responses were monitored. In 2000,
      water was drawn down on Agassiz Pool, one of the main pools on the Refuge. This
      presented an opportunity to evaluate the response of trace element concentrations
      in the diet and tissues of tree swallows after reflooding. High concentrations of
      trace elements were not detected in swallow tissues, nor were there differences
      among locations. Less than 20% of swallow samples had detectable concentrations
      of cadmium or chromium. Mercury concentrations were low and averaged <0.25
      microg/g dry wgt. in swallow tissues. Trace elements, including mercury, did not
      increase in tree swallows following the 2000 drawdown at Agassiz Pool. Hatching
      success and survival of nestlings to 12 days-of-age for tree swallows on the
      Refuge were similar to the national average and consistent with background trace
      element concentrations. Bioindicator measurements were within the normal ranges
      as well.

PMID- 16897546
TI  - Temperature effect on migration of Zn and Cd through natural clay.
AB  - To investigate the effect of temperature on effective diffusion coefficients and
      retardation factors for Zn and Cd, combined diffusion and sequential extraction
      analyses were conducted at 15 degrees C and 55 degrees C. The effective diffusion
      coefficients of the metals increased up to ten times according to the increased
      temperature. On the other hand, the effect of temperature on the retardation
      factor depended on the retention mechanisms of the metals. The distribution
      coefficient for Zn, which was mainly partitioned in the carbonate phase,
      increased up to two times with the increase in temperature. On the other hand,
      the distribution coefficient for Cd, which was mainly partitioned in the
      exchangeable phase, was hardly affected by the temperature change. Results of
      combined diffusion and sequential extraction analysis showed that the effect of
      temperature on the heavy metals' (Zn and Cd) migration through the compacted
      natural clay was influenced by the combined effects of the diffusion coefficient
      and the retardation factor. Additionally, we could also observe the change in
      retention mechanism for the metals with the change in pore water concentration.

PMID- 16897547
TI  - Assessment of the usefulness of semipermeable membrane devices for long-term
      watershed monitoring in an urban slough system.
AB  - Semipermeable membrane devices (SPMDs) were deployed at eight sites within the
      Buffalo Slough, near Portland, Oregon, to (1) measure the spatial and seasonal
      distribution of dissolved polycyclic aromatic hydrocarbon (PAH) and
      organochlorine (OC) compounds in the slough, (2) assess the usefulness of SPMDs
      as a tool for investigating and monitoring hydrophobic compounds throughout the
      Columbia Slough system, and (3) evaluate the utility of SPMDs as a tool for
      measuring the long-term effects of watershed improvement activities. Data from
      the SPMDs revealed clear spatial and seasonal differences in water quality within
      the slough and indicate that for hydrophobic compounds, this time-integrated
      passive-sampling technique is a useful tool for long-term watershed monitoring.
      In addition, the data suggest that a spiking rate of 2-5 microg/SPMD of
      permeability/performance reference compounds, including at least one compound
      that is not susceptible to photodegradation, may be optimum for the conditions
      encountered here.

PMID- 16897548
TI  - Metal contamination in urban soils of coastal Tuscany (Italy).
AB  - Urban soils are often contaminated by metals deriving from human activities.
      Urban polluted soils can affect human health through direct physical contact or
      through the food chain. The behaviour of metals is affected by chemical and
      physical soil properties. Heavy metal concentration was determined in some soils
      of three medium sized towns of coastal Tuscany, Central Italy. Soil samples were
      collected in roadsides, urban agricultural soils (allotments), playgrounds and
      public parks. The analysis included total metal content (Pb, Cu, Zn, Ni, Cd), and
      sequential extraction. Lead reached the highest levels in the soils and was
      higher near roads. In urban agricultural soils and in allotments Cu was present
      in noticeable quantities (300 mg kg(-1)). The presence of Cu in urban soils seems
      to be typical of soils used for a long period as agricultural land, especially
      vineyards in the area covered by this study. Sequential extraction was performed
      to evaluate the mobility of the metals and to better understand the impact of the
      anthropogenic activity on urban sites. In the present study principal components
      analysis (PCA) is employed to describe the characteristics of urban soils.

PMID- 16897549
TI  - A fuzzy logic approach to assess groundwater pollution levels below agricultural
      fields.
AB  - A fuzzy logic approach has been developed to assess the groundwater pollution
      levels below agricultural fields. The data collected for Kumluca Plain of Turkey
      have been utilized to develop the approach. The plain is known with its intensive
      agricultural activities, which imply excessive application of fertilizers. The
      characteristics of the soils and underlying groundwater for this plain were
      monitored during the years 1999 and 2000. Additionally, an extensive field survey
      related to the types and yields of crops, fertilizer application and irrigation
      water was carried out. Both the soil and groundwater have exhibited high levels
      of nitrogen, phosphorus and salinity with considerable spatial and temporal
      variations. The pollution level of groundwater at several established stations
      within the plain were assessed using Fuzzy Logic. Water Pollution Index (WPI)
      values are calculated by Fuzzy Logic utilizing the most significant groundwater
      pollutants in the area namely nitrite, nitrate and orthophosphate together with
      the groundwater vulnerability to pollution. The results of the calculated WPI and
      the monitoring study have yielded good agreement. WPI indicated high to moderate
      water pollution levels at Kumluca plain depending on factors such as agricultural
      age, depth to groundwater, soil characteristics and vulnerability of groundwater
      to pollution. Fuzzy Logic approach has shown to be a practical, simple and useful
      tool to assess groundwater pollution levels.

PMID- 16897550
TI  - Little Egrets (Egretta garzetta) and trace-metal contamination in wetlands of
      China.
AB  - The rapidly developing Asian countries may face threatening environmental
      contamination, that however remains largely unassessed. We studied persistent
      trace elements in three wetlands, Poyang Lake, relatively unpolluted, and Tai
      Lake, and Pearl River Delta, selected as hotspots of pollution in Central China.
      We adopted as indicator the Little Egret, a widespread colonial waterbird, and
      during 1999 and 2000 we collected and analysed the same samples as for a parallel
      study we conducted in Pakistan, e.g. eggs, body feathers of chicks, prey
      spontaneously regurgitated by the chicks, and sediments at the areas most used by
      foraging egrets. The levels of trace-metals at our three study areas were
      similar, or within the range, of those found in the few other studies for East
      Asia, with few exceptions. The concentrations of the various elements were below
      the threshold that may affect the survival or reproduction of the birds, and even
      the highest concentrations relative to background, i.e. Se in eggs, and Hg in
      feathers at Pearl Delta, do not pose toxic hazards. In sediments, the levels of
      trace elements were lower than the critical levels assumed for contaminated soil,
      except for alarming high levels of As at Poyang. These results do not confirm our
      expectation, that Poyang was relatively uncontaminated, while Tai and Pearl were
      polluted. Although trace metal concentration differed significantly among the
      three study areas, these differences were minor and were not consistent among
      elements and samples. The bioaccumulation ratios from sediments through prey,
      feather and egg, were consistent with our previous findings for Pakistan. Only Hg
      exhibited high bioaccumulation, while Se and Zn had low accumulation, and the
      other elements no accumulation. This reasserts that feathers of predators such as
      egrets, may be more sensitive indicators of environmental contamination for the
      elements subject to bioaccumulation, whereas the sediments or the organisms low
      in the food chain are better indicators for the other elements.

PMID- 16897551
TI  - Seasonal variations of PM10 and TSP in residential and industrial sites in an
      urban area of Kolkata, India.
AB  - The objective of the study is to investigate seasonal and spatial variations of
      PM10 (particulate matter with aerodynamic diameter less than or equal to 10
      microm) and TSP (total suspended particulate matter) of an Indian Metropolis with
      high pollution and population density from November 2003 to November 2004.
      Ambient concentration measurements of PM10 and TSP were carried out at two
      monitoring sites of an urban region of Kolkata. Monitoring sites have been
      selected based on the dominant activities of the area. Meteorological parameters
      such as wind speed, wind direction, rainfall, temperature and relative humidity
      were also collected simultaneously during the sampling period from Indian
      Meteorological Department, Kolkata. The 24 h average concentrations of PM10 and
      TSP were found in the range 68.2-280.6 microg/m3 and 139.3-580.3 microg/m3 for
      residential (Kasba) area, while 62.4-401.2 microg/m3 and 125.7-732.1 microg/m3
      for industrial (Cossipore) area, respectively. Winter concentrations of
      particulate pollutants were higher than other seasons, irrespective of the
      monitoring sites. It indicates a longer residence time of particulates in the
      atmosphere during winter due to low winds and low mixing height. Spread of air
      pollution sources and non-uniform mixing conditions in an urban area often result
      in spatial variation of pollutant concentrations. The higher particulate
      pollution at industrial area may be attributed due to resuspension of road dust,
      soil dust, automobile traffic and nearby industrial emissions. Particle size
      analysis result shows that PM10 is about 52% of TSP at residential area and 54%
      at industrial area.

PMID- 16897552
TI  - The contamination levels of organochlorine pesticides in water and sediment
      samples in Uluabat Lake, Turkey.
AB  - The Uluabat Lake is a reservoir of 125 km2 surface area, in the boundaries of
      Bursa province, Turkey. The results showed that Uluabat Lake was still
      contaminated by organochlorine pesticides and their residues despite the
      existence of bans over a long time. Considerable amounts of organochlorine
      pesticides (HCB, p.p'-DDT, p.p'-DDE, alpha-, beta- and gamma-BHC, Aldrin,
      Heptachlor epoxide, Endrin, Endosulfan I and II) were detected in water and
      sediment samples during one-year study in this lake. Samples of water and
      sediment were collected in different regions, (6 sampling point) of the lake
      between February 2002 and November 2002. The mean levels of organochlorine
      pesticides in water and sediments were determined. According to results, it was
      found that various environs in Uluabat Lake were contaminated by 11 different
      organochlorine pesticides. Residue analyses showed that higher organochlorine
      pesticides and their residues were generally more accumulated in the sediment
      samples.

PMID- 16897553
TI  - Seasonal bacteriological analysis of Gola river water contaminated with pulp
      paper mill waste in Uttaranchal, India.
AB  - The seasonal physico-chemical and microbial quality of Gola river water has been
      analyzed after confluence of pulp paper mill waste. The study revealed that it
      has enhanced 20-30 times pollution load of BOD, COD, TDS, TSS, sulphate,
      chloride, sodium, nitrate, potassium, lignin and phenol after mixing of pulp
      paper mill waste with river water in all season. Further, it induced the
      bacterial growth by increasing most probable number value of E. coli was 1.57 x
      10(4), 1.6 x 10(4), 1.37 x 10(4) and SPC count was 1.68 x 10(4), 1.64 x 10(4),
      1.67 x 10(4)/100 ml during summer, monsoon, winter respectively. While the most
      probable number value in river water before mixing of pulp paper mill waste was
      1.4 x 10(2), 1.82 x 10(2), 1.5 x 10(2) and SPC count was 2.8 x 10(3), 2.89 x
      10(3), 2.78 x 10(3)/100 ml during summer, monsoon and winter respectively. This
      indicated from 88-114 fold increase in most probable number value of E. coli and
      56.55-60.0 times increase in SPC count of river water after mixing of effluent in
      summer, monsoon and winter. Moreover, the most probable number value in effluent
      itself before mixing was 3.4 x 10(2), 3.3 x 10(2), 2.8 x 10(2) and SPC count was
      6 x 10(4), 6.5 x 10(4), 6 x 10(4)/100 ml during summer, monsoon, winter,
      respectively. Furthermore, it was revealed that the seasonal variation also
      regulated the bacterial population dynamics as per the physico-chemical quality,
      in which E. coli was found highest at the rate of (5.9 x 10(4)), E. aerogenes
      (5.3 x 10(4)), P. aeruginosa (1.3 x 10(4)), S. aureus (3.2 x 10(3)), K.
      pneumoniae (2.6 x 10(4)), Enteritidis (1.1 x 10(4)) on monsoon season and V.
      cholerae (7.4 x 10(2)), V. vulnificus (9.2 x 10(2))/100 ml in river water when
      contaminated with pulp paper mill waste in monsoon season. Thus, the monsoon
      season showed presence of FC and TC indicated the thermo-tolerant and disease
      causing group of bacterial population in effluent and its sequence was observed
      as monsoon>summer>winter. This indicated the growth of many pathogenic and non
      pathogenic bacteria for health hazards with contamination of pulp paper waste in
      aquatic ecosystem within the vicinity of pulp paper mill industry.

PMID- 16897554
TI  - The emissions of major aromatic VOC as landfill gas from urban landfill sites in
      Korea.
AB  - In this study, concentrations of major aromatic VOCs were determined from
      landfill gas (LFG) at a total of five municipal landfill sites in Korea including
      Nan Ji (NJ), Woon Jung (WJ), Sam Poong (SP), Hoei Chun (HC), and No Hyung (NH).
      The concentration levels of those VOC were found to be significantly different,
      mainly as a function of such a parameter as landfill aging. The VOC
      concentrations measured from the unclosed landfill sites (e.g., WJ) were
      characterized by exceedingly high values above a few tens of ppm. However, the
      results of the abandoned site (e.g., SP) were about three orders of magnitude
      lower than the others so as to merely exceed the typical ambient concentration
      levels. It was most striking to find a systematic dominance of toluene over other
      aromatic VOC under most circumstances. The LFG flux values of all aromatic VOC
      and the four specific major ones (termed as BTEX: benzene, toluene, ethylbenzene,
      and xylene) were also computed for each vent pipe from all study sites using
      their concentrations and the concurrently determined environmental parameters.
      The results, if calculated in terms of the average BTEX quantity emitted per vent
      pipe, showed that the magnitude of their emissions can vary substantially, with
      the values ranging from 0.05 (SP) to 49.2 kg yr(-1) (WJ in wintertime). The LFG
      flux values of aromatic VOC, when compared to the contribution of non-methane
      hydrocarbons (NMHC), were able to explain a constant, but minor, proportion of
      the LFG carbon budget.

PMID- 16897555
TI  - Evaluation of noise pollution in urban parks.
AB  - The present study provides an evaluation of noise pollution in six Urban Parks
      located in the city of Curitiba, Brazil. Equivalent noise levels (L(eq)) were
      measured in 303 points (each point measured during 3 min) spread throughout the
      Parks. Measured values were confronted with local legislation (Law 10625) allowed
      limits, and the Parks were thus classified as "acoustically polluted or
      unpolluted". Measured values were also evaluated according to international
      legislation: Decree no. 12 of the City Council of Rome, DIN 18005 for German
      cities, the World Health Organization, and the United States Environmental
      Protection Agency. Urban parks in the downtown area of Curitiba, surrounded by
      roads of heavy traffic and in the midst of intense commercial activities, do not
      satisfy any of the standards used. The most noise-polluted parks in Curitiba were
      the Public Walk Park and the Botanical Garden Park, with measured L(eq) of 64.8
      dB(A) and 67 dB(A).

PMID- 16897556
TI  - Leachate characterization and assessment of groundwater pollution near municipal
      solid waste landfill site.
AB  - Leachate and groundwater samples were collected from Gazipur landfill-site and
      its adjacent area to study the possible impact of leachate percolation on
      groundwater quality. Concentration of various physico-chemical parameters
      including heavy metal (Cd, Cr, Cu, Fe, Ni, Pb and Zn) and microbiological
      parameters (total coliform (TC) and faecal coliform (FC)) were determined in
      groundwater and leachate samples. The moderately high concentrations of Cl-, NO3(
      ), SO4(2-), NH4(+), Phenol, Fe, Zn and COD in groundwater, likely indicate that
      groundwater quality is being significantly affected by leachate percolation.
      Further they proved to be as tracers for groundwater contamination. The effect of
      depth and distance of the well from the pollution source was also investigated.
      The presence of TC and FC in groundwater warns for the groundwater quality and
      thus renders the associated aquifer unreliable for domestic water supply and
      other uses. Although some remedial measures are suggested to reduce further
      groundwater contamination via leachate percolation, the present study demand for
      the proper management of waste in Delhi.

PMID- 16897557
TI  - Survey of levels of phthalate ester plasticizers in a sewage lagoon effluent and
      a receiving stream.
AB  - In this study, samples from a sewage treatment lagoon and those from a receiving
      stream were analyzed for their phthalate esters content. Knowledge of the
      distribution of ubiquitous phthalate esters in the sewage lagoon and the
      receiving stream was necessary because of the reports of their subtle toxicity to
      aquatic biota and humans. Liquid-liquid extraction, Clean-up experiment and High
      Performance Liquid Chromatography (HPLC) were the methods employed for the
      quantitative determination of the Phthalates. A study of uncontaminated water was
      done to establish blank levels. The sewage lagoon and the receiving stream were
      grossly polluted as several phthalate ester plasticizers: DMP, DEP, DPhP, DBP,
      DEHP, DOP and DINP were found present at monthly mean levels of between 24.02
      mg/L and 139.25 mg/L in the sewage treatment lagoon and 10.41 mg/L and 80.53 mg/L
      in the receiving stream. The results showed higher levels of phthalate esters in
      the sewage lagoon compared to the receiving stream. The sewage lagoon was
      identified as a pollution point source into the receiving stream. Levels of
      phthalates obtained from the receiving stream are much higher than the water
      criteria of 3 microg/L phthalates recommended by the United States Environmental
      Protection Agency (USEPA) for the protection of fish and other aquatic life in
      water and the Suggested No-Adverse Effect Levels (SNAEL) of 7.5-38.5 microg/L for
      drinking water. This should give cause for great environmental concern. Peoples'
      health downstream is at stake and so is the 'health' of the ecosystem.

PMID- 16897558
TI  - What do the theories of Egon Brunswik have to say to medical education?
AB  - Every day physicians make judgments about patient management and diagnosis based
      on less than perfect information from many different sources. Judgment and
      decision-making research has taught us a great deal about such decisions, but
      these insights rarely find their way into the medical curriculum. One productive
      line of investigation in the study of judgment and decision making has followed
      the insights and theories developed by the psychologist, Egon Brunswik. His
      theories are becoming increasingly relevant to modern judgment problems. In this
      paper, I outline Brunswik's theories, trace their development over the last 50
      years and speculate on what role they should play in medical education.

PMID- 16897559
TI  - Influence of learning resources on study time and achievement scores in a problem
      based curriculum.
AB  - Many aspects of the problem-based learning cycle aim at stimulating students to
      elaborate on their knowledge. This elaborative process is considered to be one of
      the most effective study aids for learning and applying information. One of the
      opportunities to stimulate this elaboration process is by offering students more,
      and more diverse, learning resources. Under laboratory conditions, increasing the
      richness and diversity of the learning materials has often been shown to support
      students in learning, remembering and applying information. In this study, a
      curricular perspective was adopted on the question whether students would benefit
      from more learning resources. Mean study times and achievement scores for 28
      problem-based courses were calculated and included in the analyses. Independent
      variables in both analyses were the number of primary learning resources (i.e.,
      resources students were recommended to study) and the number of supplementary
      resources (i.e., related, but non-essential resources). Results showed a
      significant increase in achievement scores for courses with more primary learning
      resources, but the effect of supplementary resources was limited.

PMID- 16897560
TI  - A commentary on the use of cut-scores to increase the emphasis of non-cognitive
      variables in medical school admissions.
AB  - The academic performance consequences of relying solely on non-cognitive factors
      for selecting applicants above a GPA and MCAT threshold have not been fully
      considered in the literature. This commentary considers the impact of using a
      "threshold approach" on academic performance as assessed with the USMLE Step 1.

PMID- 16897561
TI  - Exophiala xenobiotica sp. nov., an opportunistic black yeast inhabiting
      environments rich in hydrocarbons.
AB  - A new black yeast species, Exophiala xenobiotica, is described, a segregant of
      the Exophiala jeanselmei complex. It is morphologically very similar to E.
      jeanselmei, though with less melanized conidiogenous cells, but deviates
      unambiguously on the basis of molecular phylogeny. The species is a relatively
      common agent of cutaneous infections in humans, whereas E. jeanselmei is
      associated with subcutaneous infections. Environmental strains of E. xenobiotica
      are frequently found in habitats rich in monoaromatic hydrocarbons and alkanes.

PMID- 16897562
TI  - Insights into the LexA regulon of Thermotogales.
AB  - The lexA genes of Thermotoga maritima and Petrotoga miotherma, both members of
      the Order Thermotogales, have been cloned and their transcriptional organization,
      as well as the functional characteristics of their encoded products, analyzed. In
      both bacterial species, the lexA gene was found to be co-transcribed together
      with another four (T. maritima) or three (P. miotherma) upstream open-reading
      frames. The P. miotherma LexA was able to bind promoters of both the cognate lexA
      encoding operon and the uvrA gene but not to that of the recA. Conversely, LexA
      protein and crude cell extracts from T. maritima were unable to bind promoters
      governing the expression of either its lexA or recA genes. In agreement with
      these observations, no functional copy of the P. miotherma LexA box,
      corresponding to the GANTN(6)GANNAC motif, seems to be present in the T. maritima
      genome. Giving support to the proposal that the evolutionary branching order of
      the Order Thermotogales is very close to that of Gram-positive bacteria, the P.
      miotherma LexA protein was still able to recognize the previously described LexA
      binding sequence for Gram-positive bacteria.

PMID- 16897563
TI  - LuxS-mediated signalling in Streptococcus anginosus and its role in biofilm
      formation.
AB  - The autoinducer-2 signal (AI-2) produced by several Gram-positive and Gram
      negative bacteria mediates interspecies communication. In this study we were able
      to identify an orthologue of luxS, required for the synthesis of AI-2 signals, in
      Streptococcus anginosus. Comparative analyses revealed conserved sequences in the
      predicted S. anginosus LuxS. Expression of luxS was highest during early
      exponential growth phase. Compared to other oral streptococci, conditioned media
      from growth of members of the anginosus group were the most efficient in inducing
      bioluminescence in Vibrio harveyi, indicative of AI-2 signalling. Disruption of
      luxS in S. anginosus resulted in a mutant deficient in biofilm formation, whereas
      no effect on planktonic growth rate was observed under various growth conditions.
      S. anginosus is part of the human flora found in biofilms of the oral cavity, as
      well as of the upper respiratory, gastrointestinal and urogenital tracts. Such
      habitats harbour large varieties of bacterial species, among which cell-cell
      communication may play an important role. S. anginosus has also been associated
      with purulent infections and cancer in the upper digestive tract. Knowledge about
      the molecular mechanisms involved in S. anginosus communication is important for
      understanding its commensalism and its pathogenic transition.

PMID- 16897564
TI  - Evidence for host plant preference by Iphiseiodes quadripilis (Acari:
      Phytoseiidae) on Citrus.
AB  - In this study, we present field and laboratory evidence on the preference of
      Iphiseiodes quadripilis (Banks) for grapefruit (Citrus paradisi Macfadyen) leaves
      compared with sweet orange (Citrus sinensis (L.) Osbeck) leaves. This preference
      was confirmed in four orchards whether leaf samples were taken from either border
      trees of contiguous grapefruit or sweet orange or interior row trees with both
      citrus species in adjacent rows. Iphiseiodes quadripilis was most abundant in
      grapefruit trees in spite of the greater abundance of the Texas citrus mite,
      Eutetranychus banksi (McGregor) (Acari: Tetranychidae) in sweet orange trees.
      Similar preference responses were observed in laboratory tests using a Y-tube
      olfactometer whether I. quadripilis were collected from sweet orange or
      grapefruit. Iphiseiodes quadripilis collected from grapefruit trees showed
      significant preference for grapefruit over sweet orange leaves in contact choice
      tests using an arena of alternating leaf strips (12 mm long x 2 mm wide) of sweet
      orange and grapefruit. However, I. quadripilis collected from sweet orange trees
      did not show preference for either grapefruit or sweet orange leaves. Based on
      these results, grapefruit leaves foster some unknown factor or factors that
      retain I. quadripilis in greater numbers compared with sweet orange leaves.

PMID- 16897565
TI  - Population models for threshold-based control of Tetranychus urticae in small
      scale Kenyan tomato fields and for evaluating weather and host plant species
      effects.
AB  - The spatial distribution of motile life stages of the two-spotted spider mite
      Tetranychus urticae Koch in Kenyan small-scale tomato fields was described by
      Taylor's power law and an enumerative sampling plan was designed for research
      purposes. The exponential increase of T. urticae populations during three growing
      seasons permits the development and use of a simple exponential model for the
      design of a threshold-based chemical control system. For this purpose, a critical
      threshold of 440 motile mites per sample unit at the end of the growing season
      (12 weeks after transplanting) was translated into a proportion of 0.83 infested
      units in sample 3, i.e. five weeks after transplanting. A sequential binomial
      sampling plan with respect to the proportion of 0.83, five weeks after
      transplanting, was designed. The exponential model was extended to account for
      the influence of weather and host plant species. Model development and parameter
      estimation were based on three data sets (Kenyan tomato fields, Italian and
      Californian strawberry fields). The model satisfactorily predicted a positive
      influence on growth rates by (i) changing the host plant from tomato to
      strawberry, and (ii) temperature, while a negative effect resulted from (iii)
      rainfall; both (ii) and (iii) are controlled by temperature-rainfall
      interactions. In contrast, the estimated parameter values did not satisfactorily
      describe the expected responses at specific temperature and rainfall values.
      Nevertheless, the model allowed the rating of host plant species in the field. A
      fourth data set from Swiss apple orchards was used to test the model, and
      population build-up on the apple host plant appeared to be higher than on
      tomatoes but lower than on strawberry.

PMID- 16897566
TI  - Brood-cell size does not influence the susceptibility of honey bees (Apis
      mellifera) to infestation by tracheal mites (Acarapis woodi).
AB  - Tracheal mites have been associated with the condition in honey bees that
      devastated colonies in Britain and Ireland in the early 1900s. The first outbreak
      of this condition, that became known as the 'Isle of Wight' disease, coincided
      with the period when brood-cell size was increased from about 5.0 mm to about 5.5
      mm in width. We undertook an inoculation experiment over a 7-day period to
      establish if the act of increasing the brood-cell size could have triggered the
      onset of tracheal mites in honey bees. The standard-sized cells used had a cell
      width of 5.44 mm and the small-sized cells a width of 5.07 mm. Using callow
      (newly emerged) bees, from three colonies that had mixed cell sizes, we compared
      the susceptibility of bees reared in standard-sized cells with that of those
      raised in small-sized cells. The results indicated similar levels of female mite
      abundance (0.49 vs. 0.52 mites per bee) and mean fecundity (4.33 vs. 4.22
      offspring per female mite), and produced no evidence of any difference in the
      overall susceptibility between the bees raised in the standard-sized cells versus
      small-sized brood cells.

PMID- 16897567
TI  - Chemical alarm and defence in the oribatid mite Collohmannia gigantea (Acari:
      Oribatida).
AB  - The multicomponent oil gland secretion of Collohmannia gigantea, a middle
      derivative mixonomatan oribatid mite, is demonstrated to possess alarm pheromonal
      and allomonal properties. Four components of the secretion, namely the
      monoterpenes neryl formate, neral, geranial and the aromatic 2-hydroxy- 6-methyl
      benzaldehyde (2,6-HMBD), showed moderate to strong alarm pheromonal activity in
      adult mites. Naturally elicited response is due to neral (about 50% of the
      secretion) and probably 2,6-HMBD (only 5% of the secretion, but strong alarm
      pheromonal activity). This is the second report of an alarm pheromone in
      Oribatida. Tridecane and pentadecane (=the hydrocarbon fraction of the secretion)
      did not evoke evident behavioural reactions, and most likely serve as solvents
      and spreading agents for the pheromonal-active components. Alarm reactions were
      characterized by a short recognition phase (waving movements with legs I),
      followed by shrinking back and panic escape from the scent source. In addition,
      all six components of the oil gland secretion, including the hydrocarbons,
      exhibited strong allomonal properties against a model oribatid predator, the
      scydmaenid beetle, Euconnus (Tetramelus) oblongus. Considering the widespread
      semiochemical properties of oil gland secretions in astigmatid mites (=a highly
      derivative oribatid group), these results furnish evidence for a phylogenetically
      early origin of defensive and communicative roles of oil gland secretions in
      oribatids. These roles include alarm communication, defence and the production of
      anti-fungal compounds.

PMID- 16897568
TI  - Ticks parasitizing wild birds in Portugal: detection of Rickettsia aeschlimannii,
      R. helvetica and R. massiliae.
AB  - From January 2002 to December 2004, 152 ticks were collected from 40 wild birds
      recovered in Santo Andre Natural Reserve and Monsanto Forestal Park, Portugal
      mainland. Five ticks species were identified from 22 species of birds, and new
      host record were provided for some species. In addition, 32 (21%) ticks were
      screened by PCR to detect infections with agents belonging to order
      Rickettsiales: Anaplasma phagocytophilum, Ehrlichia chaffeensis, and Rickettsia
      spp. PCR amplicons were obtained in 5 (15.6%) tick samples. Rickettsia DNA
      exhibiting gltA sequences similar to those of Rickettsia aeschilimannii, R.
      helvetica and R. massiliae were identified in Hyalomma marginatum, Ixodes
      ventalloi and in Rhipicephalus turanicus, respectively. This is the first report
      of rickettsiae infections in ticks collected from wild birds in Portugal. Giving
      the results presented above wild birds play an important role in the maintenance
      and dissemination of several tick species and associated rickettsiae.

PMID- 16897569
TI  - A partnership in like-minded thinking-generating hopefulness in persons with
      cancer.
AB  - A conceptual model of a partnership in 'like-minded thinking' consists of the
      following components: a relationship, a shared goal with mutual agreement to work
      toward that goal, and reciprocal encouragement between two people. A like-minded
      alliance is a relationship that offers support while at the same time encourages
      hope and establishes a reciprocating emotional attitude of hopefulness. The
      discussion focuses on the principles of such a model that is designed primarily
      as a lay intervention for anyone who has a close friend with cancer and who wants
      to assist the friend in maintaining a hopeful attitude in the face of illness.
      While this model is not directed at healthcare professionals it may be
      transferable into psychosocial interventions to assist persons toward sustaining
      hopefulness in the context of the cancer trajectory. Much has been written in the
      literature about how hopelessness spawns despair for individuals who have cancer
      and in those near the end of life; it may even create a desire for hastened death
      (Breitbart W., Heller K.S.: 2003, 'Reframing Hope: Meaning-Centered Care for
      Patients Near the End of Life'. Journal of Palliative Medicine 6, 979-988; Jones
      J.M., Huggins M.A., Rydall A.C., Rodin G.M.: 2003, 'Symptomatic distress,
      hopelessness, and the desire for hastened death in hospitalized cancer patients',
      Journal of Psychosomatic Research 55, 411-418). Therefore, the aim of this paper
      is to explore how like-minded thinking for a person with cancer and his or her
      support person provides a framework for a personal shared worldview that is hope
      based, meaningful and coherent.

PMID- 16897570
TI  - Causes of illness in clinical practice: a conceptual exploration.
AB  - This paper explores causation in the context of health care practice, in
      particular, primary care. Causation in health care is necessarily premised on the
      concepts of disease and illness and the ways they are deviations from health. The
      paper reviews and broadly categorises concepts of illness most commonly found in
      the literature in terms of the biomedical, biopsychosocial, and agency models. It
      is argued that although each model has its place in the gamut of health care
      practice, primary care implicitly or explicitly uses an agency model most
      frequently. By explicitly acknowledging the role that patients' values and
      expectations have in utilising their physiological, psychological and social
      capacities to live their lives, clinicians can gain a clearer understanding of
      how a situation has come about and why it has become a health problem for the
      patient.

PMID- 16897571
TI  - Causal thinking and causal language in health care: introduction to the theme.

PMID- 16897572
TI  - Functional roles of the gamma subunit of the skeletal muscle DHP-receptor.
AB  - In excitation-contraction coupling (EC coupling) of skeletal muscle, large and
      rapid changes of the myoplasmic Ca2+ concentration mediate the activation and
      termination of force. The L-type Ca2+ channel (dihydropyridine receptor, DHP
      receptor) is a central component of the EC coupling process. Its predominant role
      is to provide the Ca2+ release channels of the sarcoplasmic reticulum (SR) with
      the sensitivity to cell membrane voltage. The DHP receptor consists of five
      different proteins (alpha1S, beta1, gamma1, delta and alpha2) whose tasks and
      functional characteristics are still incompletely understood. This short review
      summarizes progress made in studying the physiology of the gamma1 subunit, a
      membrane polypeptide that is highly specific for skeletal muscle. The focus is on
      recent results obtained from muscle of gamma1-deficient mice.

PMID- 16897573
TI  - Elementary Ca2+ release events in mammalian skeletal muscle: effects of the
      anaesthetic drug thiopental.
AB  - We examined the effect of clinically relevant doses of thiopental (10-100 microM)
      on Ca2+ release from the sarcoplasmic reticulum of chemically skinned skeletal
      muscle fibres of the mouse. Elementary Ca2+ release events (ECRE) were recorded
      with confocal microscopy and were detected and analysed by an automated
      algorithm. Thiopental at 25 microM evoked a marked increase in ECRE frequency
      (events/100 microm/s) from 0.64 +/- 0.32 to 1.56 +/- 0.38 (P < 0.001). Incubation
      with 5 microM ryanodine significantly reduced spontaneous and evoked ECRE
      frequencies to 0.08 +/- 0.08 (P < 0.001) and 0.39 +/- 0.25 (25 microM thiopental,
      P < 0.001) respectively. Thiopental-evoked ECRE show different morphological
      characteristics compared to spontaneous events. Maximum relative amplitudes
      (DeltaF/F0)max and spatial width (full width at half maximum) of the events were
      substantially increased. Full duration at half maximum was increased and some
      very long events (200 ms compared to approximately 30 ms standard) were produced.
      The rise times as an indicator of the channel open time were slightly increased.
      Furthermore, the occurrence of repetitive ECRE was observed. These events, in
      contrast to previous observations in amphibian skeletal muscle fibres, displayed
      a multitude of different release patterns. In particular, a repetitive ECRE mode
      with successively decaying amplitudes was identified and the inter-event
      intervals were analysed. Estimation of the underlying Ca2+ release current
      suggests that during repetitive events with a decaying amplitude a decreasing
      amount of Ca2+ was released within the individual release event. Possible
      underlying mechanisms are discussed. In summary, thiopental seems to be a potent
      RyR1 agonist and substantially alters the gating mechanisms of RyR Ca2+ release
      channel clusters already in clinically relevant doses, i.e. doses administered
      during general anaesthesia.

PMID- 16897574
TI  - Protein kinase-A phosphorylates titin in human heart muscle and reduces
      myofibrillar passive tension.
AB  - Protein kinase-A (PKA) is activated during beta-adrenergic stimulation of the
      heart and is known to phosphorylate several sarcomeric proteins including the
      giant polypeptide titin. A PKA phosphorylation site on titin is located within
      the N2B-unique sequence, which is present in the elastic segment of the two major
      isoforms of cardiac titin, N2B and N2BA, but not in the skeletal-muscle isoforms
      of the N2A-type. In bovine and rat cardiomyocytes, PKA-mediated phosphorylation
      decreases passive tension (PT), an effect ascribed to titin phosphorylation.
      Whether titin is phosphorylated by PKA upon beta-adrenergic stimulation in human
      heart has not been shown to date. Here we report that PKA induces phosphorylation
      of N2B and N2BA titin isoforms, as well as a characteristic proteolytic fragment
      of titin, T2, in human donor hearts. The PKA-induced phosphorylation signals were
      stronger when myofilaments were first de-phosphorylated by protein phosphatase-1,
      suggesting inherent phosphorylation of titin in human heart. Titin
      phosphorylation was associated with a reduction in PT of skinned human cardiac
      strips; the relative decrease was higher at shorter than at longer physiological
      sarcomere lengths. The PKA-dependent PT drop was substantially larger when fibers
      were pre-treated with protein phosphatase-1, indicating that inherent
      phosphorylation of titin is important for the basal myocardial PT level.
      Mechanical measurements on isolated myofibrils from rat heart confirmed the PKA
      effect on passive stiffness and also showed a more pronounced effect in the
      presence of reducing agent, DTT. In contrast, PKA did not alter the PT of single
      skinned rat diaphragm muscle fibers; however, the kinase was still able to
      phosphorylate the skeletal N2A-titin isoform, which lacks the N2B-unique
      sequence. Thus, an additional phosphorylation site in titin may exist outside the
      cardiac N2B-unique sequence. We conclude that PKA mediates phosphorylation of
      titin in normal human myocardium. Titin phosphorylation lowers titin-based
      passive stiffness in heart but not in skeletal muscle.

PMID- 16897575
TI  - Effect of changes in action potential spike configuration, junctional
      sarcoplasmic reticulum micro-architecture and altered t-tubule structure in human
      heart failure.
AB  - Using a Monte-Carlo model of L-type Ca2+ channel (DHPR) gating, we have examined
      the effect of changes in the early time course of the action potential as seen in
      human heart failure on excitation contraction coupling. The time course of DHPR
      Ca2+ influx was coupled into a simple model of sarcoplasmic reticulum Ca2+
      release. Our model shows that the loss of the initial spike in human heart
      failure should reduce the synchrony of Ca2+ spark production and lead to the
      appearance of late Ca2+ sparks and greater non-uniformity of intracellular Ca2+.
      Within the junctional space of the cardiac dyad, a small increase in the mean
      distance of a DHPR from a RyR results in a marked decrease in the ability of the
      DHPR-mediated increase in local [Ca2+] concentration to activate RyRs. This
      suggests that the efficiency of EC coupling may be reduced if changes in micro
      architecture develop and such effects have been noted in experimental models of
      heart failure. High resolution imaging of t-tubules in tachycardia-induced heart
      failure show deranged t-tubule structure. While in normal human hearts t-tubules
      run mainly in a radial direction, t-tubules in the heart failure samples were
      oriented more toward the long axis of the cell. In addition, t-tubules may become
      dilated and bifurcated. Our data suggest that changes in the micro-architecture
      of the cell and membrane structures associated with excitation-contraction
      coupling, combined with changes in early action potential configuration can
      reduce the efficiency by which Ca2+ influx via DHPRs can activate SR calcium
      release and cardiac contraction. While the underlying cause of these effects is
      unclear, our data suggest that geometric factors can play an important role in
      the pathophysilogy of the human heart in failure.

PMID- 16897577
TI  - Mechanical properties of sarcomeres during cardiac myofibrillar relaxation:
      stretch-induced cross-bridge detachment contributes to early diastolic filling.
AB  - Sudden Ca2+ removal from isometrically contracting cardiac myofibrils induces a
      biphasic relaxation: first a slow, linear force decline during which sarcomeres
      remain isometric and then a rapid, exponential decay originating from sequential
      lengthening, i.e., successive mechanical relaxation, of individual sarcomeres
      (Stehle et al. 2002; Biophys J 83:2152-2162). Step-stretches were applied to the
      myofibrils, in order to study the mechanical properties of sarcomeres during this
      dynamic relaxation process. Stretch applied soon (approximately 10 ms) after Ca2+
      removal accelerated the initiation of the rapid, exponential force decay and of
      the sequential sarcomere lengthening. After the stretch, a short, transient
      period (approximately 24 ms) remained, during which time force was enhanced and
      sarcomeres were homogenously elongated by the stretch. This period was similar to
      the duration of the switching-off of troponin C in myofibrils, as measured by
      stopped-flow. In contrast, when the stretch was applied during the rapid,
      exponential relaxation phase, force quickly decayed after stretch, back to the
      force level of isometric controls or even lower. Smaller stretches lengthened
      only those sarcomeres that were located at the wave front of the sequential
      sarcomere relaxation. The more the stretch-size was increased, the more of the
      contracting sarcomeres became lengthened by the stretch; those sarcomeres that
      were relaxed prior to stretch were barely elongated. These results indicate that
      the stretch accelerates myofibrillar relaxation by forcing the cross-bridges in
      contracting sarcomeres to detach. Subsequent rapid cross-bridge reattachment
      occurs during a short period after Ca2+ removal until troponin C is switched off.
      However, this switch off occurs approximately 5 times too fast to directly rate
      limit the force relaxation under the isometric condition. After troponin C is
      switched off, stretching induces cross-bridge detachment without subsequent
      reattachment, and force rapidly decays below the isometric level. This may
      explain the rapid distention of the ventricular myocardium during early diastolic
      filling.

PMID- 16897576
TI  - New insights in the regulation of calcium transfers by muscle dystrophin-based
      cytoskeleton: implications in DMD.
AB  - Calcium mishandling in Duchenne muscular dystrophy (DMD) suggested that
      dystrophin, a membrane-associated cytoskeleton protein, may regulate calcium
      signalling cascades such as calcium entries. Calcium overload in human DMD
      myotubes is dependent on their contractile activity suggesting the involvement of
      channels being activated during contraction and/or calcium release. Forced
      expression of mini-dystrophin in dystrophin-deficient myotubes, reactivates
      appropriate sarcolemmal expression of dystrophin-associated proteins and restores
      normal calcium handling in the cytosol. Furthermore, the recombinant mini
      dystrophin reduced the store-operated calcium influx across the sarcolemma, and
      the mitochondrial calcium uptake during this influx. A slow component of calcium
      release dependent on IP3R, as well as the production of IP3, were also reduced to
      normal levels by expression of mini-dystrophin. Our studies provide a new model
      for the convergent regulation of transmembrane calcium influx and IP3-dependent
      calcium release by the dystrophin-based cytoskeleton (DBC). We also suggest
      molecular association of such channels with DBC which may provide the scaffold
      for assembling a multiprotein-signalling complex that modulates the channel
      activity. This suggests that the loss of this molecular association could
      participate in the alteration of calcium homeostasis observed in DMD muscle
      cells.

PMID- 16897578
TI  - Towards discovering dual functional inhibitors against both wild type and K103N
      mutant HIV-1 reverse transcriptases: molecular docking and QSAR studies on 4,1
      benzoxazepinone analogues.
AB  - To find useful information for discovering dual functional inhibitors against
      both wild type (WT) and K103N mutant reverse transcriptases (RTs) of HIV-1,
      molecular docking and 3D-QSAR approaches were applied to a set of twenty-five 4,1
      benzoxazepinone analogues of efavirenz (SUSTIVA), some of them are active against
      the two RTs. 3D-QSAR models were constructed, based on their binding
      conformations determined by molecular docking, with r(2)(cv) values ranging from
      0.656 to 0.834 for CoMFA and CoMSIA, respectively. The models were then validated
      to be highly predictive and extrapolative by inhibitors in two test sets with
      different molecular skeletons. Furthermore, CoMFA models were found to be well
      matched with the binding sites of both WT and K103N RTs. Finally, a reasonable
      pharmacophore model of 4,1-benzoxazepinones were established. The application of
      the model not only successfully differentiated the experimentally determined
      inhibitors from non-inhibitors, but also discovered two potent inhibitors from
      the compound database SPECS. On the basis of both the 3D-QSAR and pharmacophore
      models, new clues for discovering and designing potent dual functional drug leads
      against HIV-1 were proposed: (i) adopting positively charged aliphatic group at
      the cis-substituent of C3; (ii) reducing the electronic density at the position
      of O4; (iii) positioning a small branched aliphatic group at position of C5; (iv)
      using the negatively charged bulky substituents at position of C7.

PMID- 16897579
TI  - ADAAPT: Amgen's data access, analysis, and prediction tools.
AB  - The Amgen's Data Access Analysis Prediction Tools (ADAAPT) system is a desktop
      decision support tool developed to provide flexible access and analysis of
      chemical and biological data. The system is platform independent, adaptable,
      easily deployed, and scalable. It consists of four main modules: access,
      analysis, prediction, and tools. The access module contains numerous user
      interfaces designed to retrieve data easily. The analysis module provides
      standard computational tools to perform property calculation, QSAR/QSPR, and
      statistical analyses. The prediction module contains in-house models to calculate
      a drug-likeness score and absorption index. Finally, the tools module provides a
      wide array of features that are of general interest to our scientists.

PMID- 16897580
TI  - A virtual active compound produced from the negative image of a ligand-binding
      pocket, and its application to in-silico drug screening.
AB  - We developed a new structure-based in-silico screening method using a negative
      image of a ligand-binding pocket and a multi-protein-compound interaction matrix.
      Based on the structure of the ligand pocket of the target protein, we designed a
      negative image, which consists of virtual atoms whose radii are close to those of
      carbon atoms. The virtual atoms fit the pocket ideally and achieve an optimal
      Coulomb interaction. A protein-compound docking program calculates the protein
      compound interaction matrix for many proteins and many compounds including the
      negative image, which can be treated as a virtual compound. With specific
      attention to a vector of docking scores for a single compound with many proteins,
      we selected a compound whose score vector was similar to that of the negative
      image as a candidate hit compound. This method was applied to representative
      target proteins and showed high database enrichment with a relatively quick
      procedure.

PMID- 16897581
TI  - Evaluating the effects of gross nitrogen mineralization, immobilization, and
      nitrification on nitrogen fertilizer availability in soil experimentally
      contaminated with diesel.
AB  - Sandy clay loam soil was contaminated with 5000 mg kg(-1) diesel, and amended
      with nitrogen (15.98 atom% (15)N) at 0, 250, 500, and 1000 mg kg(-1) to determine
      gross rates of nitrogen transformations during diesel biodegradation at varying
      soil water potentials. The observed water potential values were -0.20, -0.47, 
      0.85, and -1.50 MPa in the 0, 250, 500, and 1000 mg kg(-1) nitrogen treatments
      respectively. Highest microbial respiration occurred in the lowest nitrogen
      treatment suggesting an inhibitory osmotic effect from higher rates of nitrogen
      application. Microbial respiration rates of 185, 169, 131, and 116 mg O(2) kg(-1)
      soil day(-1) were observed in the 250, 500, control and 1000 mg kg(-1) nitrogen
      treatments, respectively. Gross nitrification was inversely related to water
      potential with rates of 0.2, 0.04, and 0.004 mg N kg(-1) soil day(-1) in the 250,
      500, and 1000 mg kg(-1) nitrogen treatments, respectively. Reduction in water
      potential did not inhibit gross nitrogen immobilization or mineralization, with
      respective immobilization rates of 2.2, 1.8, and 1.8 mg N kg(-1) soil day(-1),
      and mineralization rates of 0.5, 0.3, and 0.3 mg N kg(-1) soil day(-1) in the
      1000, 500, and 250 mg kg(-1) nitrogen treatments, respectively. Based on nitrogen
      transformation rates, the duration of fertilizer contribution to the inorganic
      nitrogen pool was estimated at 0.9, 1.9, and 3.2 years in the 250, 500, and 1000
      mg kg(-1) nitrogen treatments, respectively. The estimation was conservative as
      ammonium fixation, gross nitrogen immobilization, and nitrification were
      considered losses of fertilizer with only gross mineralization of organic
      nitrogen contributing to the most active portion of the nitrogen pool.

PMID- 16897582
TI  - Involvement of platelet glycoprotein Ib in platelet microparticle mediated
      neutrophil activation.
AB  - Platelet microparticles (MPs) are membrane vesicles shed by platelets after
      activation, and carry antigens characteristic of intact platelets, such as
      glycoprotein (GP) IIb/IIIa, GPIb and P-selectin. Elevated platelet MPs have been
      observed in many disorders in which platelet activation is documented. Recently,
      platelet GPIb has been implicated in the mediation of platelet-leukocyte
      interaction via binding to its ligand Mac-1 on leukocyte. The role of GPIb for
      mediating adhesion-activation interactions between platelet MPs and leukocytes
      has not been clarified. In this study we investigate the role of GPIb in the
      interplay between platelet MPs and neutrophils. Platelet MPs were obtained from
      collagen-stimulated platelet-rich plasma (PRP). In a study model of neutrophil
      aggregation, platelet MPs can serve a bridge to support neutrophil aggregation
      under venous level shear stress, suggesting that platelet MPs may enhance
      leukocyte aggregation, which would bear clinical relevance in diseases where the
      platelet MPs are elevated. The level of aggregation can be reduced by GPIb
      blocking antibodies, AP1 and SZ2, but not by anti-CD18 mAb. The GPIb blocking
      antibodies also decreased platelet MP-mediated neutrophil activation, including
      beta2 integrin expression, adherence-dependent superoxide release and platelet MP
      mediated neutrophil adherence to immobilized fibrinogen. Our data provide the
      evidence for the involvement of GPIb-Mac-1 interaction in the cross-talk between
      platelet MPs and neutrophils.

PMID- 16897584
TI  - Effect of pepstatin A on the virulence factors of Candida albicans strains
      isolated from vaginal environment of patients in three different clinical
      conditions.
AB  - The aspartate proteinase inhibitor pepstatin A was used to study a possible
      correlation among proteinase activity and other virulence factors of Candida
      albicans strains isolated from the vaginal environment of patients in three
      different clinical conditions: asympthomatic, vulvovaginal candidiasis (VVC) and
      recurrent vulvovaginal candidiasis (RVVC). The addition of 1.0 muM pepstatin A
      did not have any significant effect on hyphae formation, biofilm production and
      in the cell surface hydrofobicity of isolates in the three different clinical
      conditions. However, pepstatin A reduced the adherence of C. albicans to vaginal
      mucosa epithelial cells (53.1, 48.7 and 59.9%, respectively to isolates from
      asymptomatic, VVC and RVVC patients). This result suggests that the secreted
      aspartate proteinases (Saps) of this fungal pathogen may have auxiliary roles in
      cellular adhesion.

PMID- 16897583
TI  - A meta-analysis of genotypes and haplotypes of methylenetetrahydrofolate
      reductase gene polymorphisms in acute lymphoblastic leukemia.
AB  - A meta-analysis of case-control studies that investigated the association between
      the C677T and/or A1298C polymorphisms in the methylenetetrahydrofolate reductase
      (MTHFR) gene and acute lymphoblastic leukemia (ALL) was carried out. Pooled odds
      ratios (OR) of various genetic contrasts of each polymorphism were estimated
      using random (RE) and fixed effects (FE) models. Pooled ORs for combined
      genotypes and haplotypes were estimated after adjustment for study effect using a
      log-linear model and the expectation-maximization algorithm in combination with
      log-linear modeling, respectively. The recessive model for allele 1298C produced
      a rather marginal association: RE OR: 0.67; 95% confidence interval (CI): 0.46
      0.99 and FE OR: 0.64; 95% CI: 0.49-0.84. In Caucasians, the results of the
      recessive model for allele 1298C was consisted with a protective effect of ALL
      development: FE OR: 0.63; 95% CI: 0.46-0.87. In childhood ALL, according to the
      results of the allele contrast and the recessive model for 677T allele it was
      conceivable that a protective effect exist: RE OR = 0.74; 95% CI: 0.57-0.96 and
      RE OR: 0.69; 95% CI: 0.51-0.94, respectively. The combined genotypes produced
      significant pooled OR for the 677CC/1298CC relative to 677CC/1298AA (OR: 0.54;
      95% CI: 0.36-0.80). The haplotype 677C/1298C might be more protective to ALL
      relative to haplotype 677C/1298A (OR: 0.77; 95% CI: 0.61-0.97). When studies not
      in Hardy-Weinberg equilibrium (HWE) were corrected to account for departures from
      HWE, then, the pattern of results remained the same. Overall, there is high
      heterogeneity between the studies in both polymorphisms. A differential magnitude
      of effect in large versus small studies and alteration of early extremes effects
      existed.

PMID- 16897586
TI  - Incidence of Tinea capitis in Sao Paulo, Brazil.
AB  - To determine the incidence of tinea capitis in Sao Paulo, Brazil, an
      investigation was performed in Private and Public Pediatrics Service involving
      4,500 children from 0 to 15 years old during 5 years (1996-2000). Samples were
      taken from 132 children with suspected fungal infection of the scalp, for direct
      microscopy and culture. Tinea of scalp was mycologically confirmed in 112
      patients (85%). Males were more affected than females in all age groups. Children
      below 8 years old accounted for more than 75% of the occurrences. Only three
      cases of tinea capitis were diagnosed in children from 12 to 15 years of age.
      Tinea capitis was prevalent in 103 cases (91.96%); inflammatory kerion type
      lesions were diagnosed in 9 patients (8.04%). Microsporum canis (70.5%) and
      Trichophyton tonsurans (23.2%) were the most common agents followed by T.
      mentagrophytes (3.6%), M. gypseum (1.8%) and T. rubrum (0.9%).

PMID- 16897585
TI  - Species diversity of yeast in oral colonization of insulin-treated diabetes
      mellitus patients.
AB  - The aim of this study was to investigate oral yeast colonization, antifungal
      susceptibility and strain diversity in insulin-dependent diabetes mellitus
      patients (175), as well as to evaluate the influence of dental prostheses. Oral
      rinse samples were cultured on selective media, in order to isolate, count and
      identify the yeasts recovered. More than half of the diabetic subjects (53%)
      carried significant amounts of Candida cells in the buccal cavity and these
      organisms were recovered at higher densities in diabetics wearing dentures. A
      total of 93 yeast strains were isolated from these patients, including: Candida
      spp. (n = 89); Pichia (n = 02); Trichosporon (n = 1), and Geotrichum (n = 1). C.
      albicans represented 56% of these strains, non-albicans Candida 39.8%, and other
      genera of yeast 4.3%. C. albicans was prevalent, followed by C. parapsilosis, C.
      tropicalis, C. glabrata, C. krusei, C. rugosa and C. guilliermondii. Agar disk
      diffusion tests of the susceptibility of non-albicans Candida and other genera of
      yeast to fluconazole showed resistance in 21.9%, mainly in C. rugosa (100%), C.
      glabrata (57%) and C. krusei (50%). Local oral factors, such as the presence of
      dentures, in association with diabetes, seemed to have the effect of increasing
      the amount and variety of Candida species in the oral cavities, mainly those with
      lower drug susceptibilities.

PMID- 16897587
TI  - Cellular immune response of patients with chromoblastomycosis undergoing
      antifungal therapy.
AB  - One of the most characteristic features of the chromoblastomycosis is its
      unresponsiveness to treatment. In order to analyzed whether during therapy could
      be observed a change of cellular immune response pattern, we evaluated the
      production of IL-10, TNF-alpha and IFN-gamma, as well as proliferation of
      peripheral blood mononuclear cell (PBMC) from patients in different periods of
      chemotherapy treatment. Our results showed that after 6 months of treatment cells
      from patients proliferated to fungal antigens and produced a significant level of
      IFN-gamma. However, after 1 year of treatment a low proliferation of T cells and
      production of IFN-gamma accompanied by an increase of IL-10 were observed when
      compared with 6 months of treatment.

PMID- 16897588
TI  - Application of fluorescent probes to study structural changes in Aspergillus
      fumigatus exposed to amphotericin B, itraconazole, and voriconazole.
AB  - The broad objective of this study was to document patterns of structural changes
      following antifungal treatment, and to determine any relationship with minimum
      inhibitory concentration (MIC) of an antifungal. Three clinical isolates of
      Aspergillus fumigatus, with high, intermediate, and low amphotericin B (AB),
      itraconazole (IZ), and voriconazole (VZ) MICs were studied in 24-well plates with
      cover slips. The fluorescent probes used were Calcofluor White (cell wall),
      propidium iodide (nucleus), and MitoTracker Green FM (mitochondria). Fluorescent
      microscopy as early as 3-h after exposure revealed that AB treated hyphae had
      intact cell wall with deformed mitochondria and nuclei while IZ and VZ treated
      hyphae revealed no intact cell wall, and deformation of mitochondria and nuclei.
      At 48 h, AB treated cells revealed rupture of hyphae and disintegration of
      mitochondria, and nuclei, IZ treated hyphae were swollen with disintegration of
      mitochondria, and nuclei while VZ treated hyphae showed rupture and
      disintegration of mitochondria and nuclei. The structural changes for the three
      strains studied were similar in fluorescent microscopy as long as the incubation
      time and their respective MICs were used. Thus, AB, IZ, and VZ induced gross
      organelle defects in A. fumigatus nuclei, mitochondria, and cell wall, which were
      consistent with respective MICs of antifungals used.

PMID- 16897589
TI  - Efficacy of voriconazole in experimental Cryptococcus neoformans infection.
AB  - Voriconazole is a third generation triazole with improved activity against many
      fungal pathogens. We examined the efficacy of voriconazole in a murine infection
      model and evaluated the drug's effect on cellular characteristics and serum
      polysaccharide levels. The antifungal reduced serum polysaccharide and
      significantly prolonged the survival of lethally infected animals.

PMID- 16897590
TI  - Susceptibility of the ant-cultivated fungus Leucoagaricus gongylophorus
      (Agaricales: Basidiomycota) towards microfungi.
AB  - The aim of this study was to select virulent strains of microfungi against
      Leucoagaricus gongylophorus, a symbiotic fungus cultivated by leaf-cutting ants.
      The results from in vitro assays showed that microfungal strains had a variable
      and significant impact on the colony development of L. gongylophorus.
      Specifically, Trichoderma harzianum, Escovopsis weberi CBS 810.71 and E. weberi
      A088 were more effective, inhibiting the L. gongylophorus colonies by 75, 68 and
      67%, respectively (P < 0.05) after 15 days. Strain E. weberi A086 and Acremonium
      kiliense were less effective: 43 and 26%, respectively (P < 0.05). In spite of
      the current negative perspective of a microbiological control approach for these
      ants, the present work discusses the possibility of using mycopathogenic fungi
      for the control of these insects, and points out the importance of encouraging
      more studies in this area.

PMID- 16897591
TI  - A direct observation technique for evaluating sclerotium germination by
      Macrophomina phaseolina and effects of biocontrol materials on survival of
      sclerotia in soil.
AB  - Germination of sclerotia of Macrophomina phaseolina was quantified by direct
      microscopic observation following application of experimental treatments in vitro
      and incubation of sclerotia in soil. To assay germination, pieces of agar
      containing sclerotia were macerated in dilute, liquid cornmeal agar on glass
      slides; thinly spread; and incubated in a saturated atmosphere for 18-22 h.
      Germinated sclerotia then were identified by morphological features of germ
      hyphae. Frequencies of germination were similar in three dilute agar media.
      Germination was not affected by air-drying sclerotia for 2 weeks, but it was
      significantly reduced after 4 weeks and greatly reduced or eliminated after 6 or
      8 weeks. Survival of sclerotia for 14 days in soil was greatest at 50, 75, and
      100% moisture-holding capacity, less at 0 and 25%, and least at 125% (flooded
      soil). Incorporation of ground poultry litter into soil at 5% by weight reduced
      survival of sclerotia after 13 days, and incorporation of litter at 10% nearly
      eliminated it. These results indicate that the direct-observation technique may
      be used to evaluate animal wastes and other agricultural byproducts for
      biocontrol activity against sclerotia of M. phaseolina in soil.

PMID- 16897592
TI  - Enhancement of sporulation in species of Bipolaris, Curvularia, Drechslera, and
      Exserohilum by growth on cellulose-containing substrates.
AB  - Nine species of Bipolaris, Curvularia, Drechslera, and Exserohilum were compared
      for sporulation on agar media and for enhancement of sporulation by growth on
      four cellulose-containing substrates (index card, filter paper, cheesecloth,
      cotton fabric). On two natural and one synthetic agar media, sporulation varied
      from profuse to nonexistent among three isolates of each species. Growth of all
      species on cellulose substrates resulted in large and significant increases in
      sporulation. Growth on index card pieces often provided the greatest increases,
      but no single substrate was superior for all species, and significant substrate x
      isolate interactions were observed within species. Overlay of filter paper onto
      whole colonies in agar plates resulted in 2 to 18-fold increases in sporulation
      for eight of nine species and production of spores in sufficient quantity for
      most experimental purposes. Overlay of soil dilution plates with filter paper to
      promote sporulation of colonies enabled detection of B. spicifera, B.
      hawaiiensis, C. lunata, and E. rostratum at relatively low population levels (<
      or =1.3 x 10(3) colony-forming units per gram of soil) in samples of a naturally
      infested soil. Results indicate that enhancement of sporulation by growth of
      species of Bipolaris, Curvularia, Drechslera, and Exserohilum on cellulose
      substrates may facilitate (i) their identification in culture, (ii) production of
      spores at relatively high concentrations, and (iii) detection and enumeration of
      these fungi in soil.

PMID- 16897593
TI  - A history of dopamine agonists. From the physiology and pharmacology of dopamine
      to therapies for prolactinomas and Parkinson's disease - a subjective view.

PMID- 16897594
TI  - Development of a Patient Questionnaire to facilitate recognition of motor and non
      motor wearing-off in Parkinson's disease.
AB  - We previously reported that the use of a specifically designed Wearing-Off
      Questionnaire (WOQ) identified symptoms of wearing-off more frequently than
      standard assessments conducted by movement disorder specialists during a routine
      office visit. In the previous study we used a WOQ of 32 symptoms; however this
      tool was not designed for daily use. In this paper we describe the retrospective
      development of a simpler, 19-symptom WOQ more suitable for routine clinical use.

PMID- 16897595
TI  - Forty-two-years later: the outcome of childhood-onset schizophrenia.
AB  - This paper describes the long-term course of 76 patients who had been
      consecutively admitted to the Department of Child and Adolescent Psychiatry,
      Philipps University, between 1920 and 1961 with a suspected diagnosis of
      childhood-onset schizophrenia. By means of a consensus analysis of available data
      in accordance with ICD-10 criteria, the diagnosis of schizophrenia was confirmed
      in only 50% of the original sample (n = 38, childhood-onset schizophrenia group);
      whereas the rest of the sample were allotted other diagnoses (n = 38, non
      schizophrenia group). A follow-up investigation was conducted, interviewing all
      available patients, if possible, or their first-degree relatives or doctors. In
      the childhood-onset schizophrenia group, age at onset (mean +/- S.D.) was 12.7 +/
      2.5 (range 5-14) years and age at follow-up was 55.0 +/- 4.8 (range 42-62)
      years. The outcome of this group was poor. According to the Global Assessment
      Scale (GAS), only 16% had a good (GAS score 71-100) and 24% had a moderate (GAS
      score 41-70) outcome. In the 16 childhood-onset schizophrenia patients who could
      be personally investigated at follow-up, 10 (62.5%) displayed severe or moderate
      depressive symptoms according to the BPRS depressive score. The death rate
      (including suicide) was significantly higher in the schizophrenia group (n = 15;
      39.5%) than in the non-schizophrenia group (n = 7; 18.4%). A comparison of the
      life-time diagnoses of the total sample (n = 76) at follow-up with the ICD-10
      diagnoses made retrospectively revealed a diagnostic stability in 69 (91%) and a
      change of diagnosis in 7 (9%) cases, among them 4 who were originally diagnosed
      as having childhood-onset schizophrenia.

PMID- 16897596
TI  - The GNB3 C825T polymorphism and depression among subjects with alcohol
      dependence.
AB  - The T allele of the C825T polymorphism in the G-protein beta(3) subunit gene
      (GNB3) is related to the increase of signal transduction by the G-protein. G
      proteins are intermediary paths in signal transduction from receptors involved in
      mood regulation and substance dependence. We studied the C825T polymorphism in
      individuals with (i) alcohol and nicotine dependence (n = 109), (ii) nicotine
      dependence only (n = 117) and (iii) non-dependent controls (n = 108). We also
      tested for possible associations with psychiatric comorbidities among alcohol
      dependent individuals. No differences were detected for allele and genotype
      frequencies in individuals with or without dependencies. Alcohol-dependent
      individuals with the heterozygous genotype presented more frequently major
      depressive disorder (chi(2) = 12.34; p = 0.002). These findings, taken together
      with other studies suggesting an influence of the C825T polymorphism in major
      depressive disorder, support the hypothesis of the involvement of G-proteins in
      mood regulation.

PMID- 16897597
TI  - Cocaine, but not amphetamine, short term treatment elevates the density of rat
      brain vesicular monoamine transporter 2.
AB  - We compared the effect of 5 days D-amphetamine (5 mg/kg/day i.p.) and cocaine (15
      mg/kg/day i.p.) administration on the vesicular monoamine transporter 2 (VMAT2)
      density in rat brain. VMAT2 expression was assessed by [(3)H]dihydrotetrabenazine
      high affinity binding. Cocaine administration led to significant increases in
      VMAT2 density in both prefrontal cortex (+40%, p < 0.01) and striatum (+23%, p <
      0.05), while amphetamine did not affect VMAT2 expression. The upregulation of
      VMAT2 may serve as compensatory mechanism aimed to enhance the vesicular
      monoamine storage capacity.

PMID- 16897598
TI  - Levels of neurotrophic factors in the hippocampus and amygdala correlate with
      anxiety- and fear-related behaviour in C57BL6 mice.
AB  - The present study tested whether individual differences in anxiety- and fear
      related behaviour are associated with between-subjects variation in postmortem
      brain levels of selected neurotrophic factors. Naive C57BL6/J mice of both sexes
      were subjected either to an elevated plus maze test or to a Pavlovian fear
      conditioning paradigm. Two days after behavioural assays, the mice were
      sacrificed for postmortem quantification of the protein levels of brain derived
      neurotrophic factors (BDNF), nerve growth factor (NGF) and neurotrophin-3 (NT-3)
      in the hippocampus and amygdala. Significant correlations between behavioural
      measures and postmortem regional neurotrophic factor contents were revealed. The
      magnitude of anxiety-like behaviour in the elevated plus maze was positively
      related to dorsal hippocampal BDNF levels, but negatively related to NGF levels
      in dorsal hippocampus and in the amygdala. On the other hand, the expression of
      conditioned fear is positively related to amygdala BDNF and NGF levels, and to
      dorsal hippocampal NGF levels. Our results add to existing reports in human as
      well as in animals of correlation between anxiety trait and gross measures of
      hippocampal volume or activation levels. Moreover, a distinction between
      spontaneous and learned (or conditioned) anxiety/fear would be relevant to the
      identification of neurotrophin signalling mechanisms in the hippocampus and
      amygdala implicated in anxiety and related psychopathology.

PMID- 16897599
TI  - An endogenous neuroprotectant substance, 1-methyl-1,2,3,4-tetrahydroisoquinoline
      (1MeTIQ), prevents the behavioral and neurochemical effects of cocaine
      reinstatement in drug-dependent rats.
AB  - Drug abuse disorder is induced by a variety of substances and results from their
      interaction with the brain reward system. It is characterized by a high frequency
      of relapse, usually associated with to craving. In this study we investigated the
      effects of 1-methyl-1,2,3,4-tetrahydroisoquinoline, an endogenous compound with
      antidopaminergic and neuroprotective activity, on cocaine-induced reinstatement
      in cocaine-dependent, self-administering rats. 1-methyl-1,2,3,4
      tetrahydroisoquinoline (50 mg/kg i.p.) completely inhibited the expression of
      reinstatement of cocaine self-administration and accompanying neurochemical
      changes induced by a single priming cocaine dose (10 mg/kg i.p.). The priming
      cocaine dose inhibited dopamine metabolism in the structures containing nerve
      endings (frontal cortex, nucleus accumbens, and striatum) but not in the
      substantia nigra and ventral tegmental area. A behaviorally active dose of 1
      methyl-1,2,3,4-tetrahydroisoquinoline administered 30 min before a priming dose
      of cocaine significantly increased the dopamine concentration in the limbic
      structures, and strongly inhibited dopamine metabolism in the substantia nigra
      and ventral tegmental area. Cocaine also inhibited noradrenaline and serotonin
      metabolism, and 1-methyl-1,2,3,4-tetrahydroisoquinoline abolished the inhibition
      in noradrenaline metabolism, while it intensified the inhibition of serotonin
      metabolism. Our results strongly support the view that 1-methyl-1,2,3,4
      tetrahydroisoquinoline, an endogenous compound, has considerable potential as a
      drug for combating substance abuse disease through the attenuation of craving.

PMID- 16897600
TI  - Kynurenine in combination with probenecid mitigates the stimulation-induced
      increase of c-fos immunoreactivity of the rat caudal trigeminal nucleus in an
      experimental migraine model.
AB  - Nitroglycerin, often used as a migraine model, results in increased number of c
      fos immunoreactive secondary sensory neurons in the caudal trigeminal nucleus.
      Since synapses between first- and second-order trigeminal neurons are mediated by
      excitatory amino acids, NMDA receptors are presumably inhibited by kynurenic
      acid, the only known endogeneous NMDA receptor antagonist. Although kynurenic
      acid does not cross the BBB, its precursor, kynurenine, if combined with
      probenecid, crosses it readily. Systemic kynurenine + probenecid treatment
      significantly diminishes nitroglycerin-induced increase of c-fos immunoreactivity
      in the brainstem.

PMID- 16897602
TI  - Interaction between catechol-O-methyltransferase (COMT) Val108/158Met and brain
      derived neurotrophic factor (BDNF) Val66Met polymorphisms in age at onset and
      clinical symptoms in schizophrenia.
AB  - Catechol-O-methyltransferase (COMT) gene is one of the candidate genes for
      schizophrenia because it codes an enzyme that participates in the metabolic
      inactivation of dopamine and noradrenaline and a limiting factor of dopamine
      metabolism in the prefrontal cortex. COMT gene lies on chromosome 22q11.2, which
      has been associated with schizophrenia susceptibility. A single-nucleotide
      polymorphism of COMT gene at position 108/158 results in an amino acid
      substitution from valine (val) to methionine (met), which modifies its enzymatic
      activity and may change the brain morphology and expressional behaviors. On the
      other hand, brain-derived neurotrophic factor (BDNF) plays a critical role in the
      development of mesolimbic dopaminergic- related systems. BDNF also contains a
      functional single-nucleotide polymorphism at codon 66 (Val66Met) of its prodomain
      and this polymorphism is responsible for schizophrenia susceptibility. In this
      study, we first investigated the relationship between COMT Val108/158Met
      polymorphism and age at onset as well as levels of clinical symptoms in 158 of
      chronic schizophrenia inpatients and then we investigated the gene-by-gene
      interaction between COMT Val108/158Met polymorphism and BDNF Val66Met
      polymorphism with age- and sex-matched control subjects (n = 318). We concluded
      that the COMT Val108/158Met polymorphism was not related to either the onset at
      age or the levels of clinical symptoms after long-term antipsychotic treatment in
      schizophrenia.

PMID- 16897601
TI  - Changes in region- and cell type-specific expression patterns of neutral amino
      acid transporter 1 (ASCT-1) in the anterior cingulate cortex and hippocampus in
      schizophrenia, bipolar disorder and major depression.
AB  - Although, the pathogenetic mechanisms of schizophrenia, bipolar disorder, and
      major depression are not clearly understood, various neurotransmitter systems are
      reported to have altered expression patterns of their receptor and transporter
      proteins. Changes in the expression of the neutral amino acid transporter 1 (ASCT
      1) protein in the anterior cingulate gyrus and the hippocampus were investigated
      using immunohistochemistry and western blotting. A significant decrease in ASCT-1
      immunoreactivity in neurons in the cingulate cortex as well as astrocytes of the
      white matter was seen in schizophrenia. In bipolar disorder and major depression,
      similar results were seen for neurons. In the hippocampus, there was a striking
      loss of immunoreactivity on astrocytes, neurons and interneurons in multiple
      regions in schizophrenia and bipolar disorder, while only minor changes were seen
      in major depression. The altered expression of ASCT-1 in neurons and astrocytes
      reflects profound changes in glutamatergic neurotransmission and highlights a
      significant role of astrocytes in the pathophysiology of neurotransmission in
      these major psychiatric disorders.

PMID- 16897604
TI  - Biological markers to predict previous alcohol withdrawal seizures: a risk
      assessment.
AB  - Recent studies have shown that both, elevated homocysteine and prolactin plasma
      levels are associated with a higher risk of alcohol withdrawal seizures. The aim
      of this study was to evaluate the predictive qualities of a combined assessment
      of homocysteine and prolactin for previous alcohol withdrawal seizures.
      Therefore, 117 male patients suffering from alcohol dependency were included into
      the study. Homocysteine was measured directly at admission, prolactin the morning
      following admission for detoxification treatment. Pearson's chi(2)-test showed
      significant results for the combined assessment of both parameters (chi(2) =
      14.71, p = 0.001). Multivariate logistic regression also revealed significant
      predictive qualities (p = 0.001, OR = 9.23, 95%CI = 2.36-36.05). A combination of
      both, homocysteine and prolactin, may help to assess the individual risk of
      alcohol withdrawal seizures in clinical practice.

PMID- 16897603
TI  - In vivo neurochemical characterization of anatoxin-a evoked dopamine release from
      striatum.
AB  - Anatoxin-a (AnTx) is a natural neurotoxin, which acts as a potent and
      stereoselective agonist at the nicotinic acetylcholine receptors. The in vivo
      actions of the AnTx on dopamine (DA) release are scarcely characterized. The aim
      of this study was to determine the neurochemical bases for AnTx-induced striatal
      DA release, using the brain microdialysis technique, in freely moving rats. Local
      application of AnTx (3.5 mM) through the microdialysis probe produced an increase
      in striatal DA levels (701 +/- 51% with respect to basal values). The effect of
      infusion of AnTx in Ca(2+)-free Ringer medium, in Na(+)-free Ringer medium and
      with TTX in the medium, was inhibited. Also, reserpine pre-treatment blocked the
      action of AnTx on striatal DA levels. To investigate the involvement of the DA
      transporter, the effects of AnTx were observed in the presence of nomifensine.
      The coadministration of AnTx and nomifensine evoked an additive effect on
      striatal DA levels. The latter results show that the DA release is not mediated
      by a decreased DA uptake. Taken as a whole, these results suggest that the
      effects of AnTx are predominantly mediated by an exocytotic mechanism, Ca(2+)-,
      Na(+)- and TTX-dependent, and not by a mechanism mediated by the DA transporter.

PMID- 16897605
TI  - Prion protein gene M129 allele is a risk factor for Alzheimer's disease.
AB  - Prion protein gene polymorphism M129V represents a known risk factor for
      Creutzfeldt-Jakob disease. Recently, the meta-analysis revealed that homozygosity
      at codon 129 is connected with increased risk of Alzheimer's disease (AD). To
      determine whether M129V polymorphism is a risk factor for AD we analyzed a group
      of early-onset, and late-onset Polish AD patients. We observed that in LOAD
      patients there is a statistically significant increase of MM (p=0.0028) and
      decrease of MV (p=0.0006) genotype frequency, as compared to controls. When both
      groups were stratified according to APOE4 status, increase of MM and decrease of
      MV genotype frequency were significant in the LOAD subgroup with no APOE4
      (p=0.017, and p=0.018, respectively). In the subgroup with APOE4 allele, only MV
      genotype frequency was significantly lower, as compared to controls (p=0.035).
      However, no interaction was found between APOE4 status and M129V polymorphism. We
      conclude that MM genotype increases LOAD risk in Polish population independently
      from the APOE4 status.

PMID- 16897606
TI  - No association between the genetic polymorphisms in the RTN4R gene and
      schizophrenia in the Chinese population.
AB  - The RTN4R gene is located in the 22q11 region and it encodes a subunit of the
      receptor complex (RTN4R-p75NTR) which results in neuronal growth inhibitory
      signals in response to Nogo-66, MAG or OMG signaling. Previous studies have
      suggested that RTN4R might act as a potential candidate for schizophrenia
      susceptibility loci. We genotyped four SNPs within the gene and conducted a case
      control study and TDT analysis, involving 707 schizophrenic patients, 689
      controls and 372 unrelated small nuclear families with schizophrenic offspring in
      the Chinese population. We examined allele and genotype frequencies and haplotype
      distributions in both family- and nonfamily-based samples. Our results suggest
      that there is no significant association between the genetic polymorphisms and
      schizophrenia in the Han Chinese population.

PMID- 16897607
TI  - Characterization of dopaminergic dysfunction in familial progressive supranuclear
      palsy: an 18F-dopa PET study.
AB  - We analyzed (18)F-dopa PET data from 11 members of kindreds with familial
      progressive supranuclear palsy (PSP) to characterize their cerebral dopaminergic
      dysfunction. Three clinically-affected PSP patients showed reduced (18)F-dopa
      uptake in the striatum, orbitofrontal cortex and amygdala. One asymptomatic
      subject exhibited progressive putamen dopaminergic dysfunction. 60% of subjects
      with abnormal (18)F-dopa scans developed PSP subsequently. This is the first in
      vivo documentation of cortical dopaminergic deficiency in PSP. Reduced striatal
      (18)F-dopa uptake in susceptible relatives may predict later clinical disease.

PMID- 16897608
TI  - Identification of an excitatory amino acid-mediated component of the ventral
      tegmental area local field potential response to medial prefrontal cortex
      stimulation: effect of acute d-amphetamine.
AB  - The induction of sensitisation to the behavioural effects of d-amphetamine - a
      model of drug addiction - involves the potentiation of exctiatory amino acid
      (EAA)-ergic synapses on dopaminergic neurons in the ventral tegmental area (VTA).
      Such potentiation has been reported as early as 2 hr post-injection, however
      earlier time points have not been assessed. Consequently, we examined the effects
      of systemic d-amphetamine on an EAA-mediated component of the VTA local field
      potential response to stimulation of the medial prefrontal cortex, an EAAergic
      afferent critical for sensitisation, over the immediate 2 hr post-injection
      period. D-amphetamine and saline both depressed the amplitude of this component
      to a similar extent throughout the recording session. It is concluded that overt
      aspects of EAA-mediated potentiation appear to be delayed with respect to drug
      administration, which may have implications for sensitisation's putative role in
      linking drug-related environmental stimuli and the central effects of the drug.

PMID- 16897609
TI  - Stimulation of D2 receptors in the prefrontal cortex reduces PCP-induced
      hyperactivity, acetylcholine release and dopamine metabolism in the nucleus
      accumbens.
AB  - The aim of the present study was to investigate the effects of stimulation of D2
      receptors in the prefrontal cortex (PFC) on spontaneous motor activity and the
      hyperactivity induced by the psychomimetic phencyclidine (PCP). In addition, the
      effects of prefrontal D2 stimulation under PCP treatment on dialysate
      concentrations of acetylcholine, choline, dopamine, DOPAC and HVA in the nucleus
      accumbens were also investigated. Sprague-Dawley male rats were implanted with
      guide cannulae to perform bilateral injections into the medial PFC of the D2
      agonist quinpirole (1.5 and 5 microg/side). Horizontal and vertical spontaneous
      motor activity and the motor activity induced by systemic injections of the PCP
      (5 mg/kg i.p.) were monitored in the open field. PFC injections of quinpirole
      (1.5 and 5 microg/side) significantly decreased horizontal and vertical
      spontaneous motor activity in a dose-related manner. These effects were blocked
      by the D2 antagonist raclopride (5 microg/side). Microinjections of quinpirole
      (1.5 and 5 microg/side) into the PFC also significantly attenuated the
      hyperactivity produced by PCP (5 mg/kg i.p.). PCP also increased dialysate
      concentrations of acetylcholine, and dopamine metabolites in the nucleus
      accumbens. These increases were also reduced by injections of quinpirole (5
      microg/side) into the PFC. These results suggest that the stimulation of
      prefrontal D2 receptors plays an inhibitory role in regulating spontaneous and
      PCP-induced motor activity and also in the neurochemical changes produced by PCP
      in the nucleus accumbens.

PMID- 16897610
TI  - Methylphenidate-induced improvements of various measures of attention in adults
      with attention deficit hyperactivity disorder.
AB  - The present study examined the effect of the stimulant medication methylphenidate
      (MPH) on attentional functioning of adults with ADHD. Sixteen adults with a
      diagnosed ADHD without comorbidity were assessed twice, at baseline off MPH and
      following MPH treatment. The assessment battery consisted of reaction time tasks
      of low complexity, including measures of alertness--subdivided into tonic and
      phasic alertness, vigilance, divided attention, flexibility and such aspects of
      selective attention as including focused attention, inhibition and integration of
      sensory information. In addition, 16 healthy participants who were matched to
      adults with ADHD according to sex, age, education level and intellectual
      functions were also assessed twice using the same test battery. The results of
      the present study suggest that adults with ADHD off stimulant medication are
      seriously impaired in various components of attention including vigilance,
      divided attention, selective attention and flexibility. These impairments of
      attention were observed primarily in regard to reaction time and its variability.
      Treatment of adults with ADHD using individually tailored doses of MPH has a
      positive effect on measures of alertness, vigilance, selective attention, divided
      attention and flexibility. However, even on MPH adults with ADHD displayed
      considerable deficits in vigilance and integration of sensory information. The
      present findings indicate that adults with ADHD are not differentially impaired
      in attentional processes but may suffer from a more global deficit of attention.
      Although MPH treatment has been found to be effective in the treatment of the
      attention deficit of adults with ADHD, additional treatment appears to be
      necessary.

PMID- 16897611
TI  - Abnormal changes of plasma acute phase proteins in schizophrenia and the relation
      between schizophrenia and haptoglobin (Hp) gene.
AB  - In this study we focused on detecting schizophrenia related changes of plasma
      proteins using proteomic technology and examining the relation between
      schizophrenia and haptoglobin (Hp) genotype. We investigated plasma proteins from
      schizophrenic subjects (n = 42) and healthy controls (n = 46) by two-dimensional
      gel electrophoresis (2-DE) in combination with mass spectrometry. To further
      reveal the genetic relationship between acute phase proteins (APPs) and
      schizophrenia disease, we tested Hp alpha1/Hp alpha2 (Hp 1/2) polymorphism and
      two single nucleotide polymorphisms (SNPs) of Hp, rs2070937 and rs5473, for
      associations with schizophrenia in the Chinese Han population. With the
      relatively high number of samples for 2-DE work, we found that four proteins in
      the family of positive APPs were all up-regulated in patients. In genetic
      association study, we found significant associations existing between
      schizophrenia and Hp polymorphisms, Hp 1/2 and rs2070937 variants. Schizophrenia
      is accompanied by both an altered expression of Hp protein and a different
      genotype distribution of Hp gene, demonstrating that Hp is associated with
      schizophrenia. The results from proteomic and genomic aspects both indicate that
      acute phase reaction is likely to be an aetiological agent in the pathophysiology
      of schizophrenia, but not just an accompanying symptom. The positive APPs are
      schizophrenic related proteins, with the highly concordant results on four
      positive APPs.

PMID- 16897615
TI  - Specific features of migraine syndrome in children.
AB  - The aim of the study was to define factors that can be used to distinguish
      migraine headaches from primary non-migraine headaches. Specific characteristics
      of headaches were analysed in 30,636 children aged 3-17; 18.97% had recurrent
      primary non-migraine headaches, whereas 8.63% had migraine headaches. Migraine
      attacks follow identical patterns (94.9%): occurring monthly (78.0%), occurring
      in morning hours (58.5%), lasting for several hours (45.1%) and ending after
      sleep (76.7%). Nausea, vomiting impulse and vomiting are basic present elements
      of migraine attacks in children. Canonical discriminate analysis defined the
      following statistically significant factors, which can distinguish migraine
      headaches from primary non-migraine headaches in children: relief after sleep
      (0.945), vomiting impulse (0.945), photophobia (0.523), nausea (0.379),
      phonophobia (0.354) and vomiting (0.330).

PMID- 16897616
TI  - Good news for chronic migraine.

PMID- 16897617
TI  - Patient confidentiality issues and accuracy of medical images used in
      publications.

PMID- 16897618
TI  - Outcome of transcutaneous electrical nerve stimulation in chronic pain: short
      term results of a double-blind, randomised, placebo-controlled trial.
AB  - The aim of this study was to test the efficacy of shortterm transcutaneous
      electrical nerve stimulation (TENS) treatment in chronic pain with respect to
      pain intensity and patients' satisfaction with treatment results. We therefore
      performed a randomised controlled trial comparing TENS and sham TENS. Patients,
      researchers and therapists were blinded for treatment allocation. One hundred and
      sixty-three patients with chronic pain referred to the Pain Centre entered the
      study. Conventional TENS and sham TENS were applied in the segments of pain, for
      a period of ten days. Outcome measures were pain intensity (visual analogue
      scale) and patients' satisfaction with treatment result (yes or no). The
      proportions of patients satisfied with treatment result differed significantly
      for TENS compared to sham TENS (58 and 42.7% respectively, chi(2)=3.8, p=0.05).
      However, no differences in pain intensity were found for patients treated with
      TENS or sham TENS. Only for patients satisfied with treatment results pain
      intensity gradually decrease equally both for TENS and sham TENS with repeated
      treatment application.

PMID- 16897619
TI  - Intracranial hypotension syndrome following chiropractic manipulation of the
      cervical spine.
AB  - Cervical spine manipulation has been associated with several disorders such as
      cervical arteries dissection, but rarely has a relationship with intracranial
      hypotension been reported. We describe a patient showing intracranial hypotension
      syndrome following chiropractic cervical spine treatment. Magnetic resonance
      showed the presence of dural leakage at cervical level, suggesting the
      pathogenesis of the syndrome. We state that cervical spine manipulation should be
      considered a treatment with risk of neurological complications, including the
      occurrence of intracranial hypotension.

PMID- 16897621
TI  - Case of microarteriovenous malformation-induced trigeminal neuralgia treated with
      radiosurgery.
AB  - Radiosurgery to the right fifth cranial nerve was performed with the Gamma Knife
      on a 39- year-old patient who presented with classic symptoms of trigeminal
      neuralgia (TN), but was found on imaging studies to harbour a small intrinsic
      vascular malformation within the nerve. Based on size and drainage, the
      arteriovenous malformation (AVM) was Spetzler-Martin Grade III and no previous
      history of bleeding was reported. The patient had failed a trial of
      carbamazepine, and no surgical procedures had been performed. A decrease in
      symptoms was reported by the 6-month follow-up. A review of the literature on
      microAVM-induced TN is provided as well as a discussion of management.

PMID- 16897622
TI  - Trigger factors of migraine and tension-type headache: experience and knowledge
      of the patients.
AB  - The objective was to examine potential trigger factors of migraine and tension
      type headache (TTH) in clinic patients and in subjects from the population and to
      compare the patients' personal experience with their theoretical knowledge. A
      cross-sectional study was carried out in a headache centre. There were 120
      subjects comprising 66 patients with migraine and 22 with TTH from a headache
      outpatient clinic and 32 persons with headache (migraine or TTH) from the
      population. A semistructured interview covering biographic data, lifestyle,
      medical history, headache characteristics and 25 potential trigger factors
      differentiating between the patients' personal experience and their theoretical
      knowledge was used. The most common trigger factors experienced by the patients
      were weather (82.5%), stress (66.7%), menstruation (51.4%) and relaxation after
      stress (50%). The vast majority of triggers occurred occasionally and not
      consistently. The patients experienced 8.9+/-4.3 trigger factors (range 0-20) and
      they knew 13.2+/-6.0 (range 1-27). The number of experienced triggers was
      smallest in the population group (p=0.002), whereas the number of triggers known
      did not differ in the three study groups. Comparing theoretical knowledge with
      personal experience showed the largest differences for oral contraceptives (65.0
      vs. 14.7%, p<0.001), chocolate (61.7 vs. 14.3%, p>0.001) and cheese (52.5 vs.
      8.4%, p<0.001). In conclusion, almost all trigger factors are experienced
      occasionally and not consistently by the majority of patients. Subjects from the
      population experience trigger factors less often than clinic patients. The
      difference between theoretical knowledge and personal experience is largest for
      oral contraceptives, chocolate and cheese.

PMID- 16897620
TI  - A review of diagnostic and functional imaging in headache.
AB  - The neuroimaging of headache patients has revolutionised our understanding of the
      pathophysiology of primary headaches and provided unique insights into these
      syndromes. Modern imaging studies point, together with the clinical picture,
      towards a central triggering cause. The early functional imaging work using
      positron emission tomography shed light on the genesis of some syndromes, and has
      recently been refined, implying that the observed activation in migraine
      (brainstem) and in several trigeminal-autonomic headaches (hypothalamic grey) is
      involved in the pain process in either a permissive or triggering manner rather
      than simply as a response to first-division nociception per se. Using the
      advanced method of voxel-based morphometry, it has been suggested that there is a
      correlation between the brain area activated specifically in acute cluster
      headache--the posterior hypothalamic grey matter--and an increase in grey matter
      in the same region. No structural changes have been found for migraine and
      medication overuse headache, whereas patients with chronic tension-type headache
      demonstrated a significant grey matter decrease in regions known to be involved
      in pain processing. Modern neuroimaging thus clearly suggests that most primary
      headache syndromes are predominantly driven from the brain, activating the
      trigeminovascular reflex and needing therapeutics that act on both sides:
      centrally and peripherally.

PMID- 16897623
TI  - Trigger factors of migraine and tension-type headache.

PMID- 16897624
TI  - Minor stroke and major vascular occlusion: advanced MRI in cerebrovascular
      patients.

PMID- 16897625
TI  - PRES: a dramatic but potentially reversible syndrome needing a prompt diagnosis.

PMID- 16897626
TI  - Pain affects the quality of life of neuropathic patients.
AB  - The aim of this study was to verify the extent to which the presence of pain
      affects the quality of life (QoL) of neuropathic patients. The patients were
      selected in our Department of Peripheral Nervous System Diseases. We enrolled 120
      consecutive patients with chronic polyneuropathy who had not received continuous
      pain therapy during the two months preceding study entry, and administered them
      the Total Neuropathy Score (TNS), the official Italian version of the SF-36 and
      the Italian Pain Questionnaire (QUID). Our main finding was that the QoL is
      affected not only by the presence of neuropathy, but also by the presence and
      intensity of pain: the physical aspect of the QoL correlated only weakly with the
      TNS, but pain was closely related to a worsening in this parameter; moreover, the
      mental domains of the SF-36 were only correlated with pain. Pain per se worsens
      the QoL of neuropathic patients, regardless of disease severity.

PMID- 16897627
TI  - Cerebral blepharoptosis: two new cases, literature review and proposal for
      diagnostic criteria.
AB  - Cerebral ptosis (CP) consists of acute and bilateral drooping eyelids due to a
      right or left middle cerebral artery territory stroke, without involvement of
      brain stem, third cranial nerve or oculosympathetic fibres. The pathogenesis of
      CP is still unknown, but most authors have hypothesised that eyelid control is
      hemispherically lateralised. Two new cases of CP and a complete literature review
      are reported in this paper. Because no unanimous criteria for CP diagnosis are
      currently available, a proposal for new criteria is also included.

PMID- 16897628
TI  - The Von Restorff effect in ageing and Alzheimer's disease.
AB  - The purpose of the study was to evaluate the Von Restorff effect in normal ageing
      and in Alzheimer's disease (AD). A shortened paradigm was administered to three
      groups of subjects: young volunteers, elderly volunteers and patients with early
      stage AD (MMSE>20). Each subject was presented with 25 lists of 10 words each,
      the target word appearing in double font size. A free recall phase followed the
      presentation of each list; after completion of the battery, a size recognition
      test was administered and subjects were inquired regarding the strategy employed
      and perception of target words. The total number of recalled words differed
      significantly among the three groups (young volunteers 144.4+/-38.6, elderly
      volunteers 86.5+/-17.6, patients 44.2+/-14.6). A significant difference in
      percentage of recall was found between target and non-target words in young
      (60.0+/-13.8% vs. 45.7%+/-15.0%, p<0.001) and in elderly (31.2+/-11.4% vs. 20.2+/
      6.9%, p<0.001) volunteers, but not in patients (10.7+/-6.9% vs. 11.8+/-7.3%). The
      present study highlights that the Von Restorff effect can be detected in healthy
      elderly subjects, and that it is significantly reduced in patients in the early
      stage of AD. On the basis of the findings of the present study it is not possible
      to disentangle the contribution of visual-perceptual and encoding impairment,
      both of them potentially contributing to the observed reduction.

PMID- 16897629
TI  - Oxcarbazepine long-term treatment retention in patients switched over from
      carbamazepine.
AB  - We evaluated the long-term outcome of oxcarbazepine (OXC) monotherapy in a
      population of patients switched over from carbamazepine (CBZ) monotherapy.
      Subjects of the study were recruited among patients who had successfully
      completed the PRIMO study, a recent multicentre Italian study that assessed the
      therapeutic equivalence of immediate (overnight) and more progressive switching
      from CBZ to OXC monotherapy in patients with partial seizures unsatisfactorily
      maintained on CBZ monotherapy due to poor tolerability or scant clinical
      efficacy. Treatment retention rate was chosen as a composite parameter for both
      efficacy and tolerance of OXC. Twelve months after having completed the PRIMO
      study, 91 of 105 patients (87%) were still taking OXC, 80 of them (76%) as
      monotherapy. Mean OXC dose was 1250+/-459 mg/day. Eighty-four out of 105 patients
      (80%) rated OXC tolerability as "good" or "very good". The mean ratio of the last
      dose of OXC to the last dose of CBZ increased from 1.54 (end of PRIMO study) to
      1.69 (end of follow-up). The large majority of a population of patients who were
      successfully switched from CBZ monotherapy to OXC monotherapy maintained OXC
      treatment for at least a further 12 months. The 1.5 OXC/CBZ ratio appears to be
      close to the optimal for the switch from CBZ to OXC, at least in patients treated
      with CBZ monotherapy.

PMID- 16897630
TI  - Hyperpyrexia-triggered relapses in an unusual case of ataxic chronic inflammatory
      demyelinating polyradiculoneuropathy.
AB  - The ataxic form of chronic inflammatory demyelinating polyradiculoneuropathy
      (ataxic-CIDP) has been recently described as a subtype of chronic ataxic
      neuropathy, distinguished by steroid responsiveness and relative preservation of
      myelinated fibres at sural nerve biopsy. We report on a case of progressive,
      predominantly sensory, steroid-responsive neuropathy with clinical, laboratory,
      electrophysiological and pathological features of this uncommon form of CIDP.
      Moreover, the present case displays peculiar hyperpyrexia-triggered relapses
      leading to transitory severe tetraparesis, bilateral facial drooping, dysphonia,
      dysphagia and dyspnoea, which leave clinicians with some unresolved questions.

PMID- 16897631
TI  - Non-ketotic hyperglycaemia-related paroxysmal bilateral hand paraesthesia
      misdiagnosed as diabetic neuropathy.
AB  - Non-ketotic hyperglycaemia (NKH)-related partial seizure disorders are not
      uncommon in clinical practice but still deserve attention as they significantly
      affect neurologic outcome if unnoticed. The atypical presentation of sensorimotor
      symptoms can be seen in this setting, with paroxysmal character as the rule.
      Atypical manifestations could cause confusion and might lead to improper
      diagnosis and treatment. We report a case of inadequately controlled diabetes
      mellitus and NKH presenting as paroxysmal paraesthesia of both hands, which was
      misdiagnosed as diabetic neuropathy.

PMID- 16897632
TI  - Minor stroke and major vascular occlusion. A case report.
AB  - Occlusion of middle cerebral artery (MCA) is generally associated to severe
      stroke and poor prognosis; however a few patients with mild to moderate
      presentation and long-term reversibility of neurological deficits have been
      reported. A 66-year-old male presented with left-side weakness and dysarthria
      (NIHSS score 7), which progressively resolved within a few days; ischaemic lesion
      of the anterior arm of the right internal capsule was found at brain CT obtained
      72 h after presentation. Transcranial Colour Doppler showed absence of flow of
      the right MCA. Cerebral angiography showed occlusion of the right MCA that was
      retrogradely revascularised by leptomeningeal collaterals. Non-invasive
      intracranial vascular examinations could identify major intracranial artery
      lesions in patients who present with mild to moderate stroke symptoms. These
      patients could be identified and followed to clarify their best treatment and
      prognosis.

PMID- 16897633
TI  - PRES: posterior or potentially reversible encephalopathy syndrome?
AB  - Posterior reversible encephalopathy syndrome (PRES) is an acronym that identifies
      a new clinico-neuroradiologic entity occurring in association with different
      conditions. We report a patient with eclamptic encephalopathy whose clinico
      radiological picture normalised after prompt treatment. We suggest defining this
      condition as potentially RES, to emphasise that reversibility is not spontaneous
      but is usually related to an adequate treatment, and that the posterior
      localisation of the lesions, even if constant, may not represent the most
      relevant finding in some patients.

PMID- 16897635
TI  - Neurologists and patients' associations: alliances and conflicts.

PMID- 16897634
TI  - Vitamin E intake and quality of life in amyotrophic lateral sclerosis patients: a
      follow-up case series study.
AB  - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder involving
      both upper and lower motor neurons, leading inexorably to death within a few
      years. Although our understanding of the pathogenesis of this disease has grown
      at a very fast rate in recent years, we do not yet have effective treatment
      options that can positively impact the quality of life (QoL) of these patients.
      Interestingly, increasing experimental evidence suggests that oxidative stress is
      involved in the pathogenesis of ALS and that vitamin E could reduce neuronal
      damage. Hence, in this observational study we determined the QoL in 33 ALS
      patients taking or not taking vitamin E supplementation (600 mg/day), using the
      Italian version of the Short-Form 36-Item Health Survey (SF-36). No differences
      were seen between the two groups of patients, therefore we do not recommend
      routine use of vitamin E in ALS patients, at least in the absence of randomised
      clinical trials specifically designed for addressing this issue.

PMID- 16897640
TI  - Incarcerated inguinal hernia presenting as spontaneous scrotal fecal fistula.
AB  - We report a case of neglected, strangulated, inguinal hernia in a middle-aged
      male, which presented as a scrotal fecal fistula. This is the first such case
      reported in an adult. The patient was treated by resection and anastamosis of the
      ileum, local debridement of the scrotum and Shouldice repair for the inguinal
      defect.

PMID- 16897641
TI  - Pelissier EP(2006) Inguinal hernia: preperitoneal placement of a memory-ring
      patch by anterior approach. Preliminary experience. Hernia 10:248-252.

PMID- 16897643
TI  - [Correction of varicocele -- laparoscopic varicocelectomy is more efficient than
      scrotal sclerosing].

PMID- 16897642
TI  - Sigmoid colonic fistula secondary to Perfix-plug, left inguinal hernia repair.
AB  - The "plug and patch" mesh herniorrhaphy has become a popular option for inguinal
      hernia repair. Previous reports have documented several complications with some
      regularity. This case presents an additional complication and offers suggestions
      as to why this complication and others might occur.

PMID- 16897644
TI  - [Invasive bladder carcinoma after prostatic carcinoma -- radical cystectomy has
      high morbidity rate].

PMID- 16897645
TI  - [Therapy of varicocele -- Cochrane meta-analysis has little statement power].

PMID- 16897646
TI  - [Prostatic punch biopsy].

PMID- 16897647
TI  - [Suprapubic cystostomy].

PMID- 16897648
TI  - Vaccine-derived polioviruses: is it time to stop using the word "rare"?

PMID- 16897649
TI  - Initial treatment of HIV infection: randomized trials with clinical end points
      are still needed.

PMID- 16897650
TI  - An outbreak of poliomyelitis caused by type 1 vaccine-derived poliovirus in
      China.
AB  - BACKGROUND: In May-July 2004, type 1 vaccine-derived poliovirus (VDPV) was
      isolated from 2 case patients with polio and a contact of a third case patient in
      Guizhou Province. METHODS: We conducted a field investigation of the outbreak,
      characterized outbreak isolates, and retrospectively reviewed national polio
      surveillance data for other VDPVs. RESULTS: Case patients were unimmunized
      children, 0.9-3.2 years old, living in 2 villages 40 km apart. Immunization
      coverage in the affected villages was very low. Isolates differed from the Sabin
      1 type by 9-11 VP1 nucleotides (1.0%-1.2%); which indicated, on the basis of
      known rates of mutation of Sabin strains, that they had been circulating for <1
      year. A province-wide immunization response targeting all children <5 years old
      was initiated in August, and the strain has not been isolated since. During 1997
      2004, 10 VDPV strains (5 of type 2, 3 of type 1, and 2 of type 3) were isolated
      from >50,000 children with acute flaccid paralysis and their contacts; 8 (80%)
      were found in southern provinces, and 9 (90%) spontaneously disappeared.
      CONCLUSION: This is the first polio outbreak in China in over a decade and the
      first due to VDPV. The short duration of circulation demonstrates the rapidity
      with which attenuated Sabin strains can revert to a wild phenotype. One to two
      VDPVs have been identified each year, primarily in densely populated subtropical
      regions of southern China. This outbreak highlights the need to consider risks of
      paralysis from vaccine-derived strains in development of national poliomyelitis
      immunization policy.

PMID- 16897651
TI  - Natural history of viral markers in children infected with human T lymphotropic
      virus type I in Jamaica.
AB  - PURPOSE: We conducted a longitudinal analysis of human T lymphotropic virus type
      I (HTLV-I) viral markers in 28 Jamaican mothers and their children, who were
      monitored for a median of 6.2 years after the birth of the children. METHODS: The
      HTLV-I provirus DNA load was measured using the Taqman system (PE Applied
      Biosystems). The HTLV-I antibody titer was determined using the Vironstika HTLV
      I/II Microelisa System (Organon Teknika). The HTLV-I Tax-specific antibody titers
      were measured using an enzyme-linked immunosorbent assay. Generalized estimating
      equations were used to describe the associations of exposure variables with
      sequentially measured levels of HTLV-I viral markers in children. RESULTS: The
      HTLV-I antibody titer increased significantly up to 1 year after infection,
      reaching equilibrium at a median titer of 1 : 7,786. The prevalence of Tax
      specific antibody reached 80% at 2 years after infection. The provirus load
      increased up to 2 years after infection, reaching equilibrium at a median of
      6,695 copies/100,000 peripheral blood mononuclear cells. The increase in the
      provirus load was significant only among children with eczema, but not among
      children without eczema. CONCLUSIONS: The provirus loads in children increased
      for an additional year after their antibody titers had stabilized, possibly as a
      result of the expansion of HTLV-I-infected clones. This effect was significant
      only for children with eczema. Among HTLV-I-infected children, eczema may be a
      cutaneous marker of the risk of HTLV-I-associated diseases developing in
      adulthood.

PMID- 16897652
TI  - Transmission of herpes simplex virus types 1 and 2 in a prospective cohort of HIV
      negative gay men: the health in men study.
AB  - BACKGROUND: Despite increasing reports of herpes simplex virus (HSV) type 1 (HSV
      1)-associated anogenital herpes, there are very limited data comparing the
      seroepidemiological profile of and risk factors for HSV-1 and HSV type 2 (HSV-2)
      infection. METHODS: Sexual behaviors were examined as risk factors for prevalent
      and incident HSV-1 and HSV-2 infections in a community-based cohort of 1,427 HIV
      negative gay men in Australia. RESULTS: The prevalence of HSV-1 and HSV-2 at
      baseline was 75% and 23%, respectively. The rate of prevalent infection with HSV
      1, as well as the rate of prevalent infection with HSV-2, was much lower in
      individuals <25 years of age, and each type of infection was associated with a
      higher number of both male and female sex partners. The median duration of follow
      up of the cohort was 2.0 years. Among participants who were susceptible to
      infection, the incidence rates for HSV-1 and HSV-2 infection were 5.58 and 1.45
      cases per 100 person-years, respectively. In multivariate analysis, incident
      infection with HSV-1 was significantly associated with younger age (P=.027) and
      reports of frequent insertive oral sex with casual partners (hazard ratio, 3.91
      [95% confidence interval, 1.23-12.44]; P=.021). Incident infection with HSV-2 was
      significantly associated with a variety of anal sex practices with casual
      partners. CONCLUSIONS: Both HSV-1 and HSV-2 were commonly sexually transmitted,
      and there were more HSV-1 than HSV-2 seroconversions. Public-health strategies
      targeted against anogenital herpes increasingly need to take into account the
      importance of HSV-1 infection.

PMID- 16897653
TI  - Subtly impaired humoral immunity predisposes to frequently recurring genital
      herpes simplex virus type 2 infection and herpetic neuralgia.
AB  - BACKGROUND: Immunogenetic factors predisposing to recurrent genital herpes remain
      poorly characterized. METHODS: In a prospective case-control study, 52
      consecutive patients with frequently recurring outbreaks of genital herpes were
      compared with 80 herpes simplex virus (HSV)-seropositive (types 1 and 2) and 70
      HSV-seronegative control subjects. Immunoglobulins (Igs), type-specific anti-HSV
      2 IgG and IgG subclass antibodies against glycoprotein G, levels of C3 and C4,
      and classical pathway hemolytic complement activity were measured, and IgG1 and
      IgG3 allotyping; C4 immunophenotyping; C4* real-time polymerase chain reaction
      (PCR) genotyping; and HLA-A*, B*, and DR* typing were performed. RESULTS: The
      G3m(g),G1m(a/a(x)) haplotype was more frequent in patients than in HSV
      seronegative control subjects (P=.047). Compared with all control subjects, low
      levels of total IgG1 (odds ratio [OR], 4.9 [95% confidence interval {CI}, 2.0
      12.5]; P=.001) and IgG3 (OR 3.6 [95% CI 1.7-7.8]; P=.001), but not of anti-HSV-2
      antibodies, were associated with recurrences. Levels of complement were lowest in
      patients. The C4* null type was negatively associated with neuralgia (OR, 0.2
      [95% CI, 0.06-0.81]; P=.022). CONCLUSIONS: Low levels of antibody-dependent
      cellular cytotoxicity-mediating IgG1 and IgG3 antibodies, partly dependent of
      allotype, may predispose to recurrent genital herpes. Antibodies produced by T
      helper type 1 responses, potentially against an unknown epitope, appear to be
      relevant in recurrences. In patients, C4* deficiencies are associated with
      protection from herpetic neuralgias, possibly through reduced inflammation.

PMID- 16897654
TI  - Characterization of human cytomegalovirus (HCMV) UL97 mutations found in a
      valganciclovir/oral ganciclovir prophylactic trial by use of a bacterial
      artificial chromosome containing the HCMV genome.
AB  - A method based on manipulation of the human cytomegalovirus genome in a bacterial
      artificial chromosome was developed to determine the role played by 6 UL97
      mutations of unknown significance. These mutations were found in blood samples
      from solid-organ transplant recipients in a trial comparing valganciclovir and
      oral ganciclovir prophylaxis. Recombinant viruses containing UL97 mutations
      P405L, A427V, M550I, A582V, Y617H, and A674T were generated in a bacterial
      system. Viral stocks were subsequently reconstituted in human fibroblasts, and
      ganciclovir susceptibilities were tested using a plaque-reduction assay. All
      recombinant viruses containing these unknown mutations were found to be
      susceptible to ganciclovir.

PMID- 16897655
TI  - A mouse monoclonal antibody against Epstein-Barr virus envelope glycoprotein 350
      prevents infection both in vitro and in vivo.
AB  - A mouse monoclonal antibody (MAb) against Epstein-Barr virus (EBV) envelope
      glycoprotein 350, 72A1, inhibited EBV infection of B lymphocytes in vitro. When
      severe combined immunodeficient mice were injected with EBV-seronegative donors'
      peripheral-blood mononuclear cells and challenged with EBV, 72A1 MAb prevented
      development of EBV-positive tumors: none of the test mice (0/12) developed EBV
      positive tumors. In contrast, 67% (8/12) of control mice developed EBV-positive
      tumors (P=.001). Purified 72A1 MAb was infused into 1 healthy adult and 4 EBV
      seronegative children after liver transplant. No adverse reactions were seen in
      the adult or in 3 of the transplant recipients. The remaining patient developed a
      hypersensitivity reaction, thus underlining the need to humanize the MAb.

PMID- 16897656
TI  - Quantitative evaluation of rotaviral antigenemia in children with acute rotaviral
      diarrhea.
AB  - BACKGROUND: Rotaviral antigen and RNA have recently been identified in the serum
      of patients with rotaviral gastroenteritis, but the roles they play in disease
      remains undetermined. METHODS: Rotaviral antigen and RNA were quantified by
      enzyme-linked immunosorbant assay and by quantitative reverse-transcription
      polymerase chain reaction in stool and serum specimens from children with
      rotaviral diarrhea (n=102), children with nonrotaviral diarrhea (n=40), and
      nondiarrheal control children (n=30). RESULTS: Rotaviral antigenemia was detected
      in 64%, 3%, and 0% of the children with rotaviral diarrhea, the children with
      nonrotaviral diarrhea, and the nondiarrheal control children, respectively. The
      level of rotaviral antigen in serum was approximately 2x10(2) -fold lower than
      that in stool, and a moderate correlation was observed between the 2 levels.
      Rotaviral RNA was detected in 93% of the antigen-positive serum specimens. The
      median number of RNA copies in serum was approximately 1 x 10(5) -fold lower than
      that in stool, and no correlation was observed between the 2 levels. Serum levels
      of both antigen and RNA were inversely associated with baseline titers of
      rotaviral serum immunoglobulin G (P<.01). Antigenemia was also associated with G1
      serotype. CONCLUSIONS: Rotaviral antigenemia and viremia were common in children
      with rotaviral diarrhea, but antigen and RNA levels in serum were substantially
      lower than those in stool. Antigenemia was associated with infection with G1
      strains and with low baseline titers of rotaviral serum antibody.

PMID- 16897657
TI  - Role of hepatitis B virus precore/core promoter mutations and serum viral load on
      noncirrhotic hepatocellular carcinoma: a case-control study.
AB  - BACKGROUND: Apart from the presence of liver cirrhosis, hepatitis B virus (HBV)
      factors have also been shown to play a role in the development of hepatocellular
      carcinoma (HCC). Studying HBV-related noncirrhotic HCC may help clarify the
      effect of viral factors. METHODS: In a hospital-based, age- and genotype-matched
      study, we aimed to determine the role played by basal core promoter (BCP)
      T1762/A1764 mutation, precore A1896 mutation, and serum viral load in
      noncirrhotic hepatocarcinogenesis by comparing 44 patients with HBV-related
      noncirrhotic HCC, 45 patients with chronic hepatitis B, and 42 patients with HBV
      related cirrhotic HCC. HBV genotype, precore and BCP mutations, and viral load
      were determined by molecular assays. RESULTS: In univariate analysis,
      statistically significant odds ratios were obtained for male sex (P=.005) and BCP
      T1762/A1764 mutation (P=.0003) in patients with noncirrhotic HCC, compared with
      patients with chronic hepatitis B. By multiple logistic regression analysis, male
      sex, BCP T1762/A1764 mutation, and viral load >or=10(5) copies/mL were
      independently associated with the risk of noncirrhotic HCC. The virologic
      characteristics were similar between patients with cirrhotic HCC and those with
      noncirrhotic HCC. CONCLUSIONS: Our results suggest that BCP T1762/A1764 mutation
      and higher viral load may be involved in the carcinogenesis of cirrhotic and
      noncirrhotic HCC.

PMID- 16897658
TI  - Cellular immune activation in children with acute dengue virus infections is
      modulated by apoptosis.
AB  - Apoptosis is an important modulator of cellular immune responses during systemic
      viral infections. Peripheral-blood mononuclear cell (PBMC) apoptosis and plasma
      soluble levels of CD95, a mediator of apoptosis, were determined in sequential
      samples from children participating in a prospective study of dengue virus (DV)
      infections. During the period of defervescence, levels of PBMC apoptosis were
      higher in children developing dengue hemorrhagic fever (DHF), the most severe
      form of illness, than in those with dengue fever (DF) and other, nondengue,
      febrile illnesses. CD8(+) T lymphocytes made up approximately half of the peak
      circulating apoptotic PBMCs in DHF and DF. Maximum plasma levels of soluble CD95
      were also higher in children with DHF than in those with DF. The level of PBMC
      apoptosis correlated with dengue disease severity. Apoptosis appears to be
      involved in modulation of the innate and adaptive immune responses to DV
      infection and is likely involved in the evolution of immune responses in other
      viral hemorrhagic fevers.

PMID- 16897659
TI  - Maternal-fetal transmission of human parvovirus B19 genotype 3.
AB  - Plasma samples obtained at delivery from 885 pregnant Ghanaian women were tested
      for human parvovirus B19 DNA and B19-specific antibodies. Maternal-fetal
      transmission was evaluated by testing paired maternal plasma and umbilical cord
      blood samples, as well as newborn whole-blood samples when they were available.
      The B19 DNA seroprevalence rate in women was 1.8% (94% had genotype 3 strains),
      and the immunoglobulin G (IgG) seroprevalence rate in women was 81%. Two of 3
      cases of primary maternal B19 infection resulted in fetal transmission.
      Coexistence of B19 DNA and B19-specific IgG (persistence) was detected in 13
      women (1.5%), but no transmission of the virus was observed. Contrary to the
      situation in pregnant women with primary B19 infection and high viral loads,
      pregnant women with low viral loads and B19-specific IgG do not appear to be
      vertically infectious.

PMID- 16897660
TI  - Rates of disease progression according to initial highly active antiretroviral
      therapy regimen: a collaborative analysis of 12 prospective cohort studies.
AB  - BACKGROUND: No large clinical end-point trials have been conducted comparing
      regimens among human immunodeficiency virus type 1-positive persons starting
      antiretroviral therapy. We examined clinical progression according to initial
      regimen in the Antiretroviral Therapy Cohort Collaboration, which is based on 12
      European and North American cohort studies. METHODS: We analyzed progression to
      death from any cause and to AIDS or death (AIDS/death), comparing efavirenz
      (EFV), nevirapine (NVP), nelfinavir, idinavir, ritonavir (RTV), RTV-boosted
      protease inhibitors (PIs), saquinavir, and abacavir. We also compared nucleoside
      reverse-transcriptase inhibitor pairs: zidovudine/lamivudine (AZT/3TC), stavudine
      (D4T)/3TC, D4T/didanosine (DDI), and others. RESULTS: A total of 17,666 treatment
      naive patients, 55,622 person-years at risk, 1,617 new AIDS events, and 895
      deaths were analyzed. Compared with EFV, the adjusted hazard ratio (HR) for
      AIDS/death was 1.28 (95% confidence interval [CI], 1.03-1.60) for NVP, 1.31 (95%
      CI, 1.01-1.71) for RTV, and 1.45 (95% CI, 1.15-1.81) for RTV-boosted PIs. For
      death, the adjusted HR for NVP was 1.65 (95% CI, 1.16-2.36). The adjusted HR for
      death for D4T/3TC was 1.35 (95% CI, 1.14-1.59), compared with AZT/3TC.
      CONCLUSIONS: Outcomes may vary across initial regimens. Results are observational
      and may have been affected by bias due to unmeasured or residual confounding.
      There is a need for large, randomized, clinical end-point trials.

PMID- 16897661
TI  - Evidence that intermittent structured treatment interruption, but not
      immunization with ALVAC-HIV vCP1452, promotes host control of HIV replication:
      the results of AIDS Clinical Trials Group 5068.
AB  - BACKGROUND: The ability to control human immunodeficiency virus (HIV) replication
      in vivo in the absence of antiretroviral therapy (ART) is a measure of the
      efficiency of antiviral immunity. In a study of patients with chronic, ART
      suppressed HIV infection, AIDS Clinical Trials Group 5068 investigated the
      effects of immunization with an exogenous HIV vaccine and pulse exposure to the
      subject's unique viral epitopes, by means of structured treatment interruptions
      (STIs), on the dynamics of viral rebound during a subsequent analytical treatment
      interruption (ATI). METHODS: Ninety-seven subjects receiving stable ART with an
      HIV-1 RNA load <50 copies/mL and CD4(+) T lymphocyte count >400 cells/mm(3) were
      randomized to undergo continued ART, STIs, ALVAC-HIV vCP1452 immunization, or
      STIs and ALVAC-HIV vCP1452 immunization. RESULTS: Subjects in the 2 STI arms had
      a significantly longer median doubling time in the period of the initial rise of
      viral load, a significantly lower median peak viral load, a significantly lower
      median end-of-ATI viral load set point, and a greater proportion of subjects with
      an end-of-ATI viral load set point <1,000 copies/mL, compared with the subjects
      in the 2 arms without STIs. With an immunization schedule of 3 sets of 3 weekly
      injections, ALVAC-HIV vCP1452 did not affect viral load measures. CONCLUSIONS: In
      this randomized, controlled study of intermittent STI as a therapeutic
      autoimmunization strategy, evidence of enhanced immunologic control of HIV
      replication was demonstrated.

PMID- 16897662
TI  - Factors associated with the development of opportunistic infections in HIV-1
      infected adults with high CD4+ cell counts: a EuroSIDA study.
AB  - BACKGROUND: Limited data exist on factors predicting the development of
      opportunistic infections (OIs) at higher-than-expected CD4(+) cell counts in
      human immunodeficiency virus (HIV) type 1-infected adults. METHODS: Multivariate
      Poisson regression models were used to determine factors related to the
      development of groups of OIs above their respective traditional upper CD4(+) cell
      count thresholds: group 1 (>or=100 cells/ microL), OIs caused by cytomegalovirus,
      Mycobacterium avium complex, and Toxoplasma gondii; group 2 (>or=200 cells/
      microL), Pneumocystis pneumonia and esophageal candidiasis; and group 3 (>or=300
      cells/ microL), pulmonary and extrapulmonary tuberculosis. RESULTS: In groups 1,
      2, and 3, 71 of 9,219, 125 of 7,934, and 36 of 7,838 patients, respectively,
      developed >or=1 intragroup OI. The strongest predictor of an OI in groups 1 and 2
      was current CD4(+) cell count (for group 1, incidence rate ratio [IRR] per 50%
      lower CD4(+) cell count, 5.37 [95% confidence interval {CI}, 3.71-7.77]; for
      group 2, 4.28 [95% CI, 2.98-6.14]). Injection drug use but not current CD4(+)
      cell count predicted risk in group 3. Use of antiretroviral treatment was
      associated with a lower incidence of OIs in all groups, likely by reducing HIV-1
      RNA levels (IRR per 1-log(10) copies/mL higher HIV-1 RNA levels for group 1, 1.50
      [95% CI, 1.15-1.95]; for group 2, 1.68 [95% CI, 1.40-2.02]; and for group 3, 1.89
      [95% CI, 1.40-2.54]). CONCLUSION: Although the absolute incidence is low, the
      current CD4(+) cell count and HIV-1 RNA level are strong predictors of most OIs
      in patients with high CD4(+) cell counts.

PMID- 16897663
TI  - Changes in body composition and mitochondrial nucleic acid content in patients
      switched from failed nucleoside analogue therapy to ritonavir-boosted indinavir
      and efavirenz.
AB  - BACKGROUND: Body composition changes complicate antiretroviral therapy.
      Improvements in lipoatrophy after a switch in nucleoside reverse-transcriptase
      inhibitors (NRTIs) have been demonstrated. We investigated 60 patients switching
      from failed NRTIs to ritonavir-boosted indinavir and efavirenz. METHODS: Body
      composition (assessed by dual-energy x-ray absorptiometry scan and by single
      slice computed tomography of the abdomen through the level of the fourth lumbar
      vertebra [L4] and the mid-right thigh) and fasted metabolics were measured at the
      baseline time-point at switch and at weeks 48 and 96 thereafter. Mitochondrial
      DNA and RNA were extracted from right-thigh subcutaneous fat and peripheral-blood
      mononuclear cells (PBMCs) at weeks 0 and 48. The primary end point was the change
      in mean limb fat over 48 weeks. RESULTS: At week 96, we observed increases in
      mean (standard deviation [SD]) limb fat (+620 [974] g; P=.003), L4 subcutaneous
      adipose tissue (+20 [35] cm(2); P<.001), mid-thigh subcutaneous adipose tissue
      (+5 [10] cm(2); P<.001), and L4 visceral adipose tissue (+11 [34] cm(2); P=.01),
      but we also observed reduced lean limb mass (-831 [1,100] g; P=.3). Mean (SD)
      mtDNA content in subcutaneous fat and in PBMCs increased (+109 [274] and +45
      [100] copies/cell, respectively). Improved virological control or immune recovery
      did not explain the results. Triglyceride, total cholesterol, estimated low
      density lipoprotein cholesterol, ratio of total cholesterol to high-density
      lipoprotein cholesterol, and blood glucose levels deteriorated (i.e., had
      increased by 206%, 67%, 58%, 19%, and 6%, respectively, at week 96). CONCLUSIONS:
      This regimen was associated with statistically significant but clinically modest
      increases in peripheral fat, visceral fat, and mitochondrial nucleic acid
      content. A predominantly adverse metabolic profile developed.

PMID- 16897664
TI  - Antagonism between the HIV-1 reverse-transcriptase mutation K65R and thymidine
      analogue mutations at the genomic level.
AB  - Prior virologic and biochemical studies have shown phenotypic antagonism between
      K65R and multiple thymidine-analogue mutations (TAMs) in site-directed mutants
      tested in vitro. We hypothesized, on the basis of this observed antagonism, that
      K65R and T215Y/F with multiple TAMs would not be selected on the same human
      immunodeficiency virus type 1 genome in vivo. We searched a large database of
      patient genotypes (n=59,262) for the frequency of K65R in combination with >or=3
      TAMs as determined by standard population sequencing. K65R and multiple TAMs were
      rarely detected (<0.1%) in the same plasma sample. Samples with both K65R and
      >or=3 TAMs (n=21) were further analyzed by use of single-genome sequencing. K65R
      was never found on the same genome with T215F/Y and >or=2 other TAMs, except in
      the presence of the Q151M multiple nucleoside reverse-transcriptase inhibitor
      (NRTI)--resistance complex. These results indicate that antagonism between the
      K65R and T215Y/F pathways of NRTI resistance occurs at the genomic level. Therapy
      with NRTI combinations that select both pathways simultaneously may delay the
      emergence of NRTI resistance and prolong treatment response.

PMID- 16897665
TI  - Low CD4+ T cell nadir is an independent predictor of lower HIV-specific immune
      responses in chronically HIV-1-infected subjects receiving highly active
      antiretroviral therapy.
AB  - The influence of CD4(+) T cell nadirs on human immunodeficiency virus (HIV)
      specific immune responses in subjects with apparently normal CD4(+) T cell counts
      is not known. We evaluated the frequency of HIV-1-specific immune responses in a
      cohort of patients with complete viral suppression (HIV-1 RNA load, <50
      copies/mL) who were receiving highly active antiretroviral therapy and had a wide
      range of CD4(+) T cell nadirs. We found positive associations between CD4(+) T
      cell nadirs and the magnitude of HIV-specific CD8(+) T cell responses (P=.02) and
      of T cell helper responses (P=.04). These data show the CD4(+) T cell nadir to be
      an independent predictor of HIV-specific CD4(+) and CD8(+) T cell responses in
      HIV-1-infected subjects with optimal suppression of viremia.

PMID- 16897666
TI  - A polymorphism that reduces RANTES expression is associated with protection from
      death in HIV-seropositive Ugandans with advanced disease.
AB  - We investigated the effect of RANTES polymorphisms on human immunodeficiency
      virus type 1 (HIV-1) disease progression in an urban population of Uganda. HIV
      positive individuals homozygous for the INT1.1C polymorphism, which had been
      associated previously with low RANTES expression, were less likely to die than
      were those with other genotypes (hazard ratio, 0.53 [95% confidence interval,
      0.33-0.83]; P=.007). This report of a non-human leukocyte antigen genetic
      association with HIV-1 and/or acquired immunodeficiency syndrome disease
      progression in an African population reveals a genetic effect different from that
      reported elsewhere for African Americans and may impact therapeutic strategies
      targeting the RANTES pathway in HIV infection.

PMID- 16897667
TI  - Signal transducer and activator of transcription factor 1 mediates apoptosis
      induced by hepatitis C virus and HIV envelope proteins in hepatocytes.
AB  - Patients coinfected with hepatitis C virus (HCV) and human immunodeficiency virus
      (HIV) have progressive liver disease that frequently leads to cirrhosis and
      death. We previously showed that hepatocytes exposed to HCV and HIV envelope
      proteins undergo apoptosis via an innocent-bystander mechanism as a result of the
      cell surface binding of these proteins, independent of direct viral infection.
      Here, we have defined the mechanism of this hepatocytic apoptosis. We observed
      enhanced signal transducer and activator of transcription factor 1 (STAT1)
      activation and phosphorylation after costimulation with HCV-E2 and HIV-gp120.
      Moreover, inhibitor studies indicated that Lyn kinase, p38 mitogen-activated
      protein kinase, and protein kinase C delta might be involved in STAT1
      phosphorylation. To elucidate the downstream STAT1-mediated signaling, we
      overexpressed wild-type STAT1 alpha and the C-terminal domain-deleted mutant
      STAT1 beta . STAT1 alpha overexpression increased cell apoptosis and Fas ligand
      expression, compared with STAT1 beta overexpression. STAT1 alpha also enhanced
      the release of cytochrome c from the mitochondria and caspase-3 activity. These
      studies indicate that the HCV/HIV envelope proteins cooperatively induce
      hepatocytic apoptosis by activating a novel downstream STAT1 signaling pathway.

PMID- 16897668
TI  - Capsular serotype-specific attack rates and duration of carriage of Streptococcus
      pneumoniae in a population of children.
AB  - BACKGROUND: The relative invasiveness rates (attack rates) of Streptococcus
      pneumoniae of different capsular serotypes in children are not known. Estimates
      of capsular serotype invasiveness (designated "invasive odds ratios") that are
      based on cross-sectional prevalence carriage data have been published, but these
      estimates could be biased by variation in the duration of carriage. METHODS: The
      relative attack rates of invasive pneumococci were measured using national UK
      surveillance data on invasive pneumococcal disease (IPD) incidence and data on
      incidence of pneumococcal acquisition from longitudinal studies of nasopharyngeal
      pneumococcal carriage. RESULTS: We found significant differences in capsular
      serotype-specific attack rates. For example, capsular serotypes 4, 14, 7F, 9V,
      and 18C were associated with rates of >20 IPD cases/100,000 acquisitions, whereas
      capsular serotypes 23F, 6A, 19F, 16F, 6B, and 15B/C were associated with <10 IPD
      cases/100,000 acquisitions. There was an inverse relationship between duration of
      carriage and attack rate by capsular serotype (P<.0001). Attack rates were
      significantly correlated with invasive odds ratios (P<.0001). CONCLUSIONS: The
      capsular serotype is a major determinant of both pneumococcal duration of
      carriage and attack rate. Published invasive odds ratios are a reliable and
      practical method of determining capsular serotype invasiveness and will be
      valuable for investigating and characterizing emerging capsular serotypes in the
      context of conjugate vaccination.

PMID- 16897669
TI  - The important role of nontypable Streptococcus pneumoniae international clones in
      acute conjunctivitis.
AB  - BACKGROUND: In a recent epidemiological study in southern Israel, nontypable
      Streptococcus pneumoniae isolates were found to be highly associated with
      sporadic cases of acute conjunctivitis (AC). The purpose of the present study was
      to evaluate the relative importance in causing AC of the absence of capsule
      versus genotype properties. METHODS: DNA typing by pulsed-field gel
      electrophoresis (PFGE) was performed on 148 nontypable organisms isolated from 3
      sites: nasopharynx of healthy children, middle-ear fluid, and conjunctiva.
      RESULTS: Analysis of the PFGE patterns revealed the presence of 6 clusters; 2
      clusters that included 44% of the isolates (65/148) were associated with AC, and
      the remaining 4 were frequently isolated from the nasopharynx. Multilocus
      sequence typing, performed on representative isolates of the 2 major clusters,
      confirmed that the organisms were pneumococci; one is a single-locus variant of
      sequence type (ST) 448, and the other is related to ST344. Both types appear to
      be members of pneumococcal lineages that have lost capsular loci. The nontypable
      isolates showed high rates of resistance to antimicrobial agents. CONCLUSIONS:
      Our data suggest that the absence of the capsule--along with other, yet
      unidentified genetic characteristics--provide S. pneumoniae with a selective
      virulence advantage in conjunctivitis.

PMID- 16897670
TI  - beta-Defensin gene expression during the course of experimental tuberculosis
      infection.
AB  - The kinetics of gene expression and the cellular source of murine beta -defensin
      3 (mBD3) and murine beta -defensin-4 (mBD4) were determined in mouse models of
      progressive pulmonary tuberculosis and latent infection induced by high or low
      infecting doses, respectively. During progressive disease, there was an initial
      rapid expression of both defensins by respiratory epithelial cells that
      correlated with temporary control of bacillary proliferation, but expression
      decreased during the later progressive phase of the disease. In latent infection,
      both defensins were expressed continuously, but they were suppressed after
      reactivation of the disease. Thus, mycobacterial infection induces the expression
      of mBD3 and mBD4, and both might participate in the control of mycobacterial
      growth.

PMID- 16897671
TI  - The 37-kDa/67-kDa laminin receptor acts as a receptor for infectious prions and
      is inhibited by polysulfated glycanes.
AB  - BACKGROUND: Recently, we showed that the 37-kDa/67-kDa laminin receptor (LRP/LR)
      acts as the receptor of the cellular prion protein. METHODS: For the present
      study, we investigated the binding of the murine scrapie prion protein (moPrP27
      30) to baby hamster kidney (BHK) cells, using the Semliki Forest virus system.
      RESULTS: The enhanced binding of moPrP27-30 to BHK cells expressing moLRP::FLAG
      was inhibited by the LRP/LR-specific antibody W3, which suggests that LRP/LR acts
      as a receptor for the scrapie form of the prion protein, PrP(Sc). This finding
      was confirmed by a parallel study that showed that bovine prions are internalized
      by human enterocytes via LRP/LR. The heparan sulfate mimetics HM5004 and HM2602
      reduced PrP27-30 binding to moLRP-expressing cells to approximately 30% and
      approximately 20%, respectively, at a concentration of 10 microg/mL, whereas
      pentosan polysulfate (SP54) and phycarin sulfate (PS3) both reduced the binding
      to approximately 40% at a concentration of 100 microg/mL. CONCLUSIONS: We suggest
      that the inhibition reported elsewhere of PrP(Sc) synthesis and the incubation
      times prolonged in rodent models by these sulfated glycans are due to the
      inhibition of the LRP/LR-dependent binding of prions to the target cells.

PMID- 16897672
TI  - Evaluation of caspofungin and amphotericin B deoxycholate against Candida
      albicans biofilms in an experimental intravascular catheter infection model.
AB  - Candida albicans biofilms complicate the treatment of infected implanted
      intravascular devices because of decreased antifungal susceptibility. In our
      investigation, 48 rabbits with experimental central venous catheter C. albicans
      infection were equally allocated to a control arm or to receive amphotericin B
      deoxycholate or caspofungin treatment while undergoing systemic and intraluminal
      lock therapy for 7 days. C. albicans was cultured from catheters from all control
      rabbits, from 3 that received amphotericin B, and from 0 that received
      caspofungin. Differences in colony counts were detected between the control and
      amphotericin (P<.001) and control and caspofungin (P<.001) arms. Caspofungin may
      be useful in the treatment of C. albicans biofilm-associated intravascular
      catheter infections, which warrants further study.

PMID- 16897673
TI  - Helicobacter pylori eradication and its effect on iron stores: a reappraisal.

PMID- 16897675
TI  - Babesia microti and Borrelia burgdorferi coinfection associated with increased
      severity of arthritis.

PMID- 16897676
TI  - No pfmdr1 amplifications in samples from Guinea-Bissau and Liberia collected
      between 1981 and 2004.

PMID- 16897678
TI  - Neonatal vitamin a supplementation: sex-differential effects on mortality?

PMID- 16897682
TI  - HUPO Publications Committee Meeting: 21 April 2006, San Francisco, CA, USA.
AB  - This meeting was convened with the aim of bringing together representatives from
      scientific journals, granting authorities, software and instrumentation
      manufacturers, data producers and database providers to discuss the
      implementation and adoption of the HUPO-PSI data standards and how these can be
      best used to support the publication and dissemination of proteomics data. The
      current status of data formats and reporting requirements was reviewed and the
      attendees agreed that the use of data standards was essential as the field of
      proteomics grows and matures.

PMID- 16897679
TI  - Functional antibody arrays through metal ion-affinity templates.

PMID- 16897684
TI  - Analysis of acidic peptides with a matrix-assisted laser desorption/ionization
      mass spectrometry using positive and negative ion modes with additive
      monoammonium phosphate.
AB  - Acidic PTMs such as phosphorylation and sulfonation of proteins are known to play
      important roles in many cellular processes including signal transductions and
      protein-protein interactions. In MS, the acidic modified peptides, that have
      negative charge, are observable in negative ion mode rather than in positive ion
      mode. Moreover, addition of ammonium salt into MALDI matrix solution improves the
      relative intensity of ionization of the phosphorylated peptide to unmodified one.
      We demonstrate that a combination of the negative ion mode and addition of
      ammonium salt is more effective in the ionization of the acidic modified
      peptides. We applied this method to 2-DE separated proteins of Caenorhabditis
      elegans. As a result, 42 spots were identified as modified proteins, of which 34
      proteins were nonoverlapping unique proteins. Furthermore, our study revealed
      that pI shifts of the DIM-1 and MLC-1 proteins in the 2-DE gel were attributed to
      the presence of the acidic modifications. The negative ion mode together with the
      addition of ammonium salt provides us a useful method to detect the
      phosphorylation and/or sulfonation of protein in a simple manner.

PMID- 16897683
TI  - Proteomics and Beyond: a report on the 3rd Annual Spring Workshop of the HUPO-PSI
      21-23 April 2006, San Francisco, CA, USA.
AB  - The theme of the third annual Spring workshop of the HUPO-PSI was "proteomics and
      beyond" and its underlying goal was to reach beyond the boundaries of the
      proteomics community to interact with groups working on the similar issues of
      developing interchange standards and minimal reporting requirements. Significant
      developments in many of the HUPO-PSI XML interchange formats, minimal reporting
      requirements and accompanying controlled vocabularies were reported, with many of
      these now feeding into the broader efforts of the Functional Genomics Experiment
      (FuGE) data model and Functional Genomics Ontology (FuGO) ontologies.

PMID- 16897685
TI  - High-coverage quantitative proteomics using amine-specific isotopic labeling.
AB  - Peptide dimethylation with isotopically coded formaldehydes was evaluated as a
      potential alternative to techniques such as the iTRAQ method for comparative
      proteomics. The isotopic labeling strategy and custom-designed protein
      quantitation software were tested using protein standards and then applied to
      measure proteins levels associated with Alzheimer's disease (AD). The method
      provided high accuracy (10% error), precision (14% RSD) and coverage (70%) when
      applied to the analysis of a standard solution of BSA by LC-MS/MS. The technique
      was then applied to measure protein abundance levels in brain tissue afflicted
      with AD relative to normal brain tissue. 2-D LC-MS analysis identified 548 unique
      proteins (p<0.05). Of these, 349 were quantified with two or more peptides that
      met the statistical criteria used in this study. Several classes of proteins
      exhibited significant changes in abundance. For example, elevated levels of
      antioxidant proteins and decreased levels of mitochondrial electron transport
      proteins were observed. The results demonstrate the utility of the labeling
      method for high-throughput quantitative analysis.

PMID- 16897686
TI  - Proteomic profiles of induced hepatotoxicity at the subcellular level.
AB  - In the present study proteomes of liver samples were analyzed after
      administration of phenobarbital (PB) or 3-methylcholantrene (3-MC) to mice. Liver
      cell homogenates were subfractionated by differential ultracentrifugation into
      cytosol and microsomes, which were subjected to 2-DE to generate the proteomic
      maps of these fractions. 2-DE yielded 1100 and 800 protein spots for microsomes
      and cytosol, respectively. General trends of the fraction-specific alterations
      after 3-MC or PB treatment were evaluated using the Student's t-test and the
      principal component analysis (PCA). According to the PCA-derived data, the
      microsomal changes after 3-MC and PB treatment were quite similar. However, in
      the case of the cytosol data, the specificities of 3-MC- and PB-induced responses
      could be clearly distinguished from each other. Protein spots, whose expression
      levels differed from control, were identified by MALDI-TOF PMF. Proteomic studies
      such as those reported herein can be useful in identifying the molecular-based
      toxicity of lead drug candidates.

PMID- 16897687
TI  - Proteomic response of Schizosaccharomyces pombe to static and oscillating
      extremely low-frequency electromagnetic fields.
AB  - There is considerable public concern regarding the health effects of exposure to
      low-frequency electromagnetic fields. In addition, the association between
      exposure and disease incidence or the possible biological effects of exposure are
      unclear. Using 2D-DIGE and MS in a blind study, we have investigated the effects
      of static and oscillating extremely low-frequency electromagnetic fields (ELF
      EMFs) on the proteomes of wild type Schizosaccharomyces pombe and a Sty1p
      deletion mutant which displays increased sensitivity to a variety of cellular
      stresses. Whilst this study identifies a number of protein isoforms that display
      significant differential expression across experimental conditions, there was no
      correlation between their patterns of expression and the ELF EMF exposure
      regimen. We conclude that there are no significant effects of either static or
      oscillating EMF on the yeast proteome at the sensitivity afforded by 2D-DIGE. We
      hypothesise that the proteins identified must be sensitive to subtle changes in
      culture and/or handling conditions, and that the identification of these proteins
      in other proteomic studies should be treated with some caution when the results
      of such studies are interpreted in a biological context.

PMID- 16897688
TI  - Applying the SAGE technique to study the effects of electromagnetic field on
      biological systems.
AB  - Identification of genes alternatively expressed in electromagnetic field (EMF)
      exposed cells could provide direct evidence for biological effects of EMF. As
      there are a few indications so far for certain genes to be influenced by EMF,
      genome-wide scans of the transcriptome appear to be necessary. Among the several
      technologies used for genome-wide gene expression analysis, serial analysis of
      gene expression (SAGE) is one promising method, which seems particularly
      applicable for EMF research. This review provides a brief description of the
      features of gene expression, illustrates the basic principle of SAGE, and
      discusses the advantages and limitations of SAGE as well as examples of
      application. This information should help investigators determine if the SAGE
      technique is an optimal method for evaluating the biological effects of EMF.

PMID- 16897689
TI  - Proton spectroscopy provides accurate pathology on biopsy and in vivo.
AB  - In the last 25 years, MR spectroscopy (MRS) has moved from being a basic research
      tool into routine clinical use. The spectroscopy method reports on those
      chemicals that are mobile on the MR time scale. Many of these chemicals reflect
      specific pathological processes but are complicated by the fact that many
      chemicals change at one time. There are currently two clinical applications for
      spectroscopy. The first is in the pathology laboratory, where it can be an
      adjunct to, and in some cases replacement, for difficult pathologies like
      Barrett's esophagus and follicular adenoma of the thyroid. The spectroscopy
      method on a breast biopsy can also report on prognostic indicators, including the
      potential for spread, from information present in the primary tumor alone. The
      second application for spectroscopy is in vivo to provide a preoperative
      diagnosis and this is now achievable for several organs including the prostate.
      The development of spectroscopy for clinical purposes has relied heavily on the
      serially-sectioned histopathology to confirm the high accuracy of the method. The
      combination of in vivo MRI, in vivo MRS, and ex vivo MRS on biopsy samples offers
      a modality of very high accuracy for preoperative diagnosis and provision of
      prognostic information for human cancers.

PMID- 16897690
TI  - Billing effectively with the new health and behavior current procedural
      terminology codes in primary care and specialty clinics.
AB  - The health and behavior current procedural terminology (CPT) codes introduced in
      2003 have gained nationwide acceptance through Medicare and limited acceptance
      through third party payers. The codes facilitate accurate description and
      quantification of behavioral medicine services within a primary care or specialty
      clinic setting. The author reviews their appropriate utilization to enhance
      reimbursement and facilitate development of self-sustaining behavioral medicine
      programs. Information is provided on increased use and reimbursement of codes
      within psychology. Future directions for continued advocacy, increased
      acceptance, training, and research are discussed.

PMID- 16897691
TI  - Eating Pattern Inventory for Children: a new self-rating questionnaire for
      preadolescents.
AB  - A questionnaire on psychological dimensions of eating behavior in children is
      presented. Existing questionnaires for children specifically focus on symptoms of
      eating disorders only, whereas for adults, questionnaires assessing general
      psychological dimensions of eating behavior are also available. The development
      of the Eating Pattern Inventory for Children (EPI-C) was based on a sample of 373
      fourth-grade students. Factor and item analysis led to a psychometrically sound
      20-item questionnaire with the dimensions dietary restraint, external eating,
      parental pressure to eat, and emotional eating. These factors explain 62% of the
      total item variance. Subscale scores and emerging eating patterns were associated
      with children's body weight suggesting initial evidence of its validity. The EPI
      C is proposed for research on eating behavior in clinical and non-clinical
      preadolescent samples.

PMID- 16897692
TI  - Artifacts and pitfalls in diffusion MRI.
AB  - Although over the last 20 years diffusion MRI has become an established technique
      with a great impact on health care and neurosciences, like any other MRI
      technique it remains subject to artifacts and pitfalls. In addition to common MRI
      artifacts, there are specific problems that one may encounter when using MRI
      scanner gradient hardware for diffusion MRI, especially in terms of eddy currents
      and sensitivity to motion. In this article we review those artifacts and pitfalls
      on a qualitative basis, and introduce possible strategies that have been
      developed to mitigate or overcome them.

PMID- 16897693
TI  - Evaluation of a cure process during alarm treatment for nocturnal enuresis.
AB  - Using a treatment package featuring the urine alarm, this study evaluated a
      treatment process for nocturnal enuresis. Children who received the training were
      classified into treatment successes (N = 38) and nonsuccesses (N = 19) according
      to a criterion (3-week continence). Their daily results were analyzed with four
      categories: dry with sleep (DS), dry with spontaneous awakening (DA), wet with
      spontaneous or alarm-forced awakening (WA), and wet with sleep (WS). In a trend
      analysis, an increase of DA over the treatment process was prominent for
      successes compared to nonsuccesses. Entering WA to a discriminant analysis, 86%
      of children were correctly classified into the two groups. The findings that
      awakening categories well distinguished successes from nonsuccesses provide
      support for an active avoidance model explaining the efficacy of urine-alarm
      treatment for nocturnal enuresis.

PMID- 16897694
TI  - Interpretation of teasing during early adolescence.
AB  - Research has suggested that teasing, especially about physical appearance, is a
      common experience with negative consequences for adolescents. This study aimed to
      examine the cognitive processes of adolescents exposed to teasing. Students from
      two middle schools were assigned randomly to view videotaped vignettes of
      appearance-related teasing, competency teasing, or a control situation and
      completed questionnaires to assess their cognitive reactions and memories of the
      teasing. Results indicated that adolescent girls recalled appearance-related
      teasing more readily than competency teasing, adolescent girls with high body
      dissatisfaction recalled fewer positive appearance words, and participants
      exposed to competency teasing were more likely to recall competency words. The
      findings indicated that cognitive processes may be important in the study of
      adolescents' interpretation of teasing and for clinical treatment of adolescents
      who are teased.

PMID- 16897695
TI  - Current posttraumatic stress disorder and history of trauma in trichotillomania.
AB  - Though some researchers and clinicians postulate that trauma and posttraumatic
      stress disorder (PTSD) may be implicated in the etiologic underpinnings of
      trichotillomania (TTM), very little research to date has examined such
      postulations. To address this gap in the literature, the current study assessed
      the prevalence of trauma and PTSD in 42 individuals seeking treatment for TTM.
      Relations between symptoms of PTSD and TTM also were examined, as were
      differences in TTM symptoms between those with and without PTSD. Findings
      revealed that approximately 76% reported a history of at least one traumatic
      event, and 19% met criteria for PTSD. Furthermore, negative correlations were
      demonstrated between symptoms of PTSD and characteristics of TTM, and the PTSD
      group reported less severe TTM characteristics. Findings suggest that the
      prevalence of PTSD in TTM may be higher than in the general population and that a
      history of greater number of types of traumas is associated with a longer
      duration of hair pulling as well as the scalp as the primary pulling site. The
      authors also speculate that in traumatized individuals, TTM may represent a form
      of coping vis-a-vis self-soothing or self-harm.

PMID- 16897696
TI  - Prescribing non-psychopharmacological agents: a new potential role for
      psychologists in primary care settings and specialty clinics.
AB  - At least 10 years have passed since the Department of Defense Psychopharmacology
      Demonstration Project graduated its first class of psychologists. All graduates
      of that program were credentialed to prescribe and the program received promising
      external reviews and audits. The profession has since moved well beyond the
      initial question, "Can and should psychologists prescribe?" posed over two
      decades ago. A number of professional schools and training institutions have
      implemented postdoctoral psychopharmacology training programs and over 20 states
      are actively pursuing legislative agendas. Given recent initiatives to provide
      health psychology services within the primary care arena, the authors introduce a
      new role in the scope of psychology's prescribing activities. They propose that
      psychopharmacological agents are not the only medications psychologists should be
      trained to prescribe and psychopharmacology training should include course work
      and supervision related to treatment within a primary care patient setting in
      addition to a traditional psychiatric one. The authors provide the rationale for
      primary care clinical health psychology training as the appropriate mechanism for
      psychopharmacology education and practice. Public health needs and
      epidemiological data provide the rationale for health psychologists additionally
      prescribing non-psychopharmacological agents.

PMID- 16897697
TI  - Coping variables that mediate the relation between intimate partner violence and
      mental health outcomes among low-income, African American women.
AB  - Coping variables that mediate the relation between intimate partner violence
      (IPV) and mental health outcomes among African American women were investigated.
      The study sample included 143 economically disadvantaged African American women
      ranging in age from 21 to 64 years old who were receiving services at an urban
      public health system. Sixty-five had experienced IPV within the past year and 78
      had never experienced IPV. Results indicated that (a) the IPV status-depressive
      symptoms link was mediated by multiple ways of coping, spiritual well-being, and
      social support; (b) the IPV status-anxiety symptoms link was mediated by multiple
      ways of coping, social support, and ability to access resources; and (c) the IPV
      status-parenting stress link was mediated by multiple ways of coping, spiritual
      well-being, and social support. Implications of these findings for clinical
      practice with abused women are discussed.

PMID- 16897698
TI  - Integrating clinical psychology into primary care settings.
AB  - The primary care setting offers a mostly new and exciting opportunity for
      clinical psychology. Historically, psychology has been relegated to the "back
      forty," distant and far removed from mainstream medicine in most major hospitals.
      The primary care integration possibilities for clinical psychology are many. The
      present article will highlight these opportunities as well as provide the reader
      with an understanding as to why this conceptual paradigm and practical shift is
      needed as well as how to integrate clinical psychology services into the primary
      care setting.

PMID- 16897700
TI  - Decreased protein tyrosine phosphorylation and membrane fluidity in spermatozoa
      from infertile men with varicocele.
AB  - Varicocele is a prevalent pathology among infertile men. The mechanisms linking
      this condition to infertility, however, are poorly understood. Our previous work
      showed a relationship between sperm functional quality and the ability of
      spermatozoa to respond to capacitating conditions with increased membrane
      fluidity and protein tyrosine phosphorylation. Given the reported association
      between varicocele, oxidative stress, and sperm dysfunction, we hypothesized that
      spermatozoa from infertile patients with varicocele might have a combined defect
      at the level of membrane fluidity and protein tyrosine phosphorylation. Semen
      samples from infertile patients with and without grade II/III left varicocele
      were evaluated for motion parameters (computer-assisted semen analysis [CASA]),
      hyperactivation (CASA), incidence and intensity of protein tyrosine
      phosphorylation (phosphotyrosine immunofluorescence and western blotting), and
      membrane fluidity (Laurdan fluorometry), before and after a capacitating
      incubation (6 hr at 37 degrees C in Ham's F10/BSA, 5% CO(2)). Spermatozoa from
      varicocele samples presented a decreased response to the capacitating challenge,
      showing significantly lower motility, hyperactivation, incidence and intensity of
      tyrosine phosphorylation, and membrane fluidity. The findings reported in this
      article indicate that the sperm dysfunction associated to infertile varicocele
      coexists with decreased sperm plasma membrane fluidity and tyrosine
      phosphorylation. These deficiencies represent potential new pathophysiological
      mechanisms underlying varicocele-related infertility.

PMID- 16897701
TI  - Ready for an orange revolution in biotechnology?

PMID- 16897706
TI  - Yeast as a drug discovery platform in Huntington's and Parkinson's diseases.
AB  - The high degree of conservation of cellular and molecular processes between the
      budding yeast Saccharomyces cerevisiae and higher eukaryotes have made it a
      valuable system for numerous studies of the basic mechanisms behind devastating
      illnesses such as cancer, infectious disease, and neurodegenerative disorders.
      Several studies in yeast have already contributed to our basic understanding of
      cellular dysfunction in both Huntington's and Parkinson's disease. Functional
      genomics approaches currently being undertaken in yeast may lead to novel
      insights into the genes and pathways that modulate neuronal cell dysfunction and
      death in these diseases. In addition, the budding yeast constitutes a valuable
      system for identification of new drug targets, both via target-based and non
      target-based drug screening. Importantly, yeast can be used as a cellular
      platform to analyze the cellular effects of candidate compounds, which is
      critical for the development of effective therapeutics. While the molecular
      mechanisms that underlie neurodegeneration will ultimately have to be tested in
      neuronal and animal models, there are several distinct advantages to using simple
      model organisms to elucidate fundamental aspects of protein aggregation, amyloid
      toxicity, and cellular dysfunction. Here, we review recent studies that have
      shown that amyloid formation by disease-causing proteins and many of the
      resulting cellular deficits can be faithfully recapitulated in yeast. In
      addition, we discuss new yeast-based techniques for screening candidate
      therapeutic compounds for Huntington's and Parkinson's diseases.

PMID- 16897707
TI  - Yeast models of human mitochondrial diseases: from molecular mechanisms to drug
      screening.
AB  - Mitochondrial diseases are rare diseases most often linked to energy in the form
      of ATP-depletion. The high number of nuclear- and mitochondrial-DNA-encoded
      proteins (>500), required for ATP production and other crucial mitochondrial
      functions such as NADH re-oxidation, explains the increasing number of reported
      disorders. In recent years, yeast has revealed to be a powerful model to identify
      responsible genes, to study primary effects of pathogenic mutations and to
      determine the molecular mechanisms leading to mitochondrial disorders. However,
      the clinical management of patients with mitochondrial disorders is still
      essentially supportive. Here we review some of the most fruitful yeast
      mitochondrial disorder models and propose to subject these models to
      highthroughput chemical library screening to prospect new therapeutic drugs
      against mitochondrial diseases.

PMID- 16897708
TI  - Inhibitors of human indoleamine 2,3-dioxygenase identified with a target-based
      screen in yeast.
AB  - Indoleamine 2,3-dioxygenase (IDO) is a tryptophan degradation enzyme that is
      emerging as an important drug target. IDO is expressed by many human tumors to
      help them escape immune detection, and it has been implicated in depression and
      in the formation of senile nuclear cataracts. There is a need for potent and
      selective IDO inhibitors for use in research and as lead compounds for drug
      development. We show that expression of human IDO in a Saccharomyces cerevisiae
      tryptophan auxotroph restricts yeast growth in the presence of low tryptophan
      concentrations and that inhibition of IDO activity can restore growth. We use
      this assay to screen for IDO inhibitors in collections of pure chemicals and
      crude natural extracts. We identify NSC 401366 (imidodicarbonimidic diamide, N
      methyl-N'-9-phenanthrenyl-, monohydrochloride) as a potent nonindolic IDO
      inhibitor (Ki=1.5 +/- 0.2 microM) that is competitive with respect to tryptophan.
      We also use this assay to identify the active compound caulerpin from a crude
      algal extract. The yeast growth restoration assay is simple and inexpensive. It
      combines desirable attributes of cell- and target-based screens and is an
      attractive tool for chemical biology and drug screening.

PMID- 16897709
TI  - Yeast as a tool to uncover the cellular targets of drugs.
AB  - Knowledge of the spectrum of cellular proteins targeted by experimental
      therapeutic agents would greatly facilitate drug development. However,
      identifying the targets of drugs is a daunting challenge. The yeast Saccharomyces
      cerevisiae is a valuable model organism for human diseases and pathways because
      it is genetically tractable and shares many functional homolog with humans. In
      yeast, it is possible to increase or decrease the expression level of essentially
      every gene and measure changes in drug sensitivity to uncover potential targets.
      It is also possible to infer mechanism of action from comparing the changes in
      mRNA expression elicited by drug treatment with those induced by gene deletions
      or by other drugs. Proteins that bind drugs directly can be identified using
      yeast protein chips. This review of the use of yeast for discovering targets of
      drugs discusses the advantages and drawbacks of each approach and how combining
      methods may reveal targets more efficiently.

PMID- 16897710
TI  - Hydrocortisone made in yeast: metabolic engineering turns a unicellular
      microorganism into a drug-synthesizing factory.
AB  - Inspired by the successful work of converting Saccharomyces cerevisiae into an
      microorganism capable of synthesizing hydrocortisone, a 27-carbon molecule, from
      ethanol, a 2-carbon molecule, this review provides an overview of the potential
      of yeast as a recombinant organism in the 21st century. Yeast has been used by
      man for more than 6,000 years, and is still paving the way to new discoveries. It
      was the first eukaryotic organism to be sequenced, in 1996, and the first to
      produce hydrocortisone in 2003. In addition, extensive genome-wide analyses have
      been performed with yeast. In this review, we discuss the pros and cons of using
      yeast to produce small therapeutic molecules. It is obvious that S. cerevisiae
      has a cutting edge advantage of being a well-known organism and time will tell if
      yeast "biohydrocortisone" is a unique example or the beginning of a long list of
      yeast bioproducts. Other organisms, such as plants and bacteria, are competing
      with yeast. Bacteria produce a wealth of marketed molecules and plants are
      capable of producing extremely complex molecules with an unbeatable yield.
      However, S. cerevisiae offers a unique mix of the simplicity of a recombinant
      organism combined with the complexity of a eukaryote.

PMID- 16897711
TI  - Heterologous expression of a plant uracil transporter in yeast: improvement of
      plasma membrane targeting in mutants of the Rsp5p ubiquitin protein ligase.
AB  - Plasma membrane proteins involved in transport processes play a crucial role in
      cell physiology. On account of these properties, these molecules are ideal
      targets for development of new therapeutic and agronomic agents. However, these
      proteins are of low abundance, which limits their study. Although yeast seems
      ideal for expressing heterologous transporters, plasma membrane proteins are
      often retained in intracellular compartments. We tried to find yeast mutants
      potentially able to improve functional expression of a whole set of heterologous
      transporters. We focused on Arabidopsis thaliana ureide transporter 1 (AtUPS1),
      previously cloned by functional complementation in yeast. Tagged versions of
      AtUPS1 remain mostly trapped in the endoplasmic reticulum and were able to reach
      slowly the plasma membrane. In contrast, untagged AtUPS1 is rapidly delivered to
      plasma membrane, where it remains in stable form. Tagged and untagged versions of
      AtUPS1 were expressed in cells deficient in the ubiquitin ligase Rsp5p, involved
      in various stages of the intracellular trafficking of membrane-bound proteins.
      rsp5 mutants displayed improved steady state amounts of untagged and tagged
      versions of AtUPS1. rsp5 cells are thus powerful tools to solve the many problems
      inherent to heterologous expression of membrane proteins in yeast, including ER
      retention.

PMID- 16897712
TI  - Antimalarial drugs - host targets (re)visited.
AB  - Every year, forty percent of the world population is at risk of contracting
      malaria. Hopes for the erradication of this disease during the 20th century were
      dashed by the ability of Plasmodium falciparum, its most deadly causative agent,
      to develop resistance to available drugs. Efforts to produce an effective vaccine
      have so far been unsuccessful, enhancing the need to develop novel antimalarial
      drugs. In this review, we summarize our knowledge concerning existing
      antimalarials, mechanisms of drug-resistance development, the use of drug
      combination strategies and the quest for novel anti-plasmodial compounds. We
      emphasize the potential role of host genes and molecules as novel targets for
      newly developed drugs. Recent results from our laboratory have shown Hepatocyte
      Growth Factor/MET signaling to be essential for the establishment of infection in
      hepatocytes. We discuss the potential use of this pathway in the prophylaxis of
      malaria infection.

PMID- 16897713
TI  - Arenicola marina extracellular hemoglobin: a new promising blood substitute.
AB  - The need to develop a blood substitute is now urgent because of the increasing
      concern over Europe's BSE outbreak and the worldwide HIV/AIDS epidemic, which
      have cut blood supplies. Extracellular soluble hemoglobin has long been studied
      for its possible use as a safe and effective alternative to blood transfusion,
      but this has met with little success. Clinical trials have revealed undesirable
      side effects-oxidative damage and vasoconstriction-that hamper the application of
      cell-free hemoglobin as a blood substitute. We have addressed these problems and
      have found a new promising extracellular blood substitute: the natural giant
      extracellular polymeric hemoglobin of the polychaete annelid Arenicola marina.
      Here we show that it is less likely to cause immunogenic response; its functional
      and structural properties should prevent the side effects often associated with
      the administration of extracellular hemoglobin. Moreover, its intrinsic
      properties are of interest for other therapeutic applications often associated
      with hemorrhagic shock (ischemia reperfusion, treatment of septic shock and for
      organ preservation prior to transplantation). Moreover, using natural hemoglobin
      is particularly useful since recombinant DNA techniques could be used to express
      the protein in large quantities.

PMID- 16897720
TI  - Hippocampal place cells: the "where" of episodic memory?
AB  - Neuropsychologists have clearly implicated the hippocampus in the consolidation
      of memory, particularly episodic memory, the mental replay of past experiences.
      When recorded from behaving animals, by far the most obvious firing pattern of
      the primary neurons of the hippocampus is the place field: a cell tends to fire
      only when the animal's head is in a particular part of its environment. It seems
      reasonable to suspect that the primary firing correlate of the primary neurons of
      a structure should underlie the primary function of that structure as revealed by
      behavioral lesion experiments. However, we are currently still at a loss to
      explain how the firing of hippocampal neurons contributes to hippocampal
      function. This review seeks to examine the commonalities between place cells and
      episodic memory, and posits that an analogy can be made between the stabilization
      of place fields and the consolidation of memory.

PMID- 16897719
TI  - Morphine conditioned place preference depends on glucocorticoid receptors in both
      hippocampus and nucleus accumbens.
AB  - Learned association between drugs of abuse and context is essential for the
      formation of drug conditioned place preference (CPP), which is believed to engage
      many brain regions including hippocampus and nucleus accumbens (NAc). The
      underlying mechanisms are not fully understood. Here, we examined whether
      glucocorticoid receptors (GRs) of hippocampus and NAc influenced the formation of
      morphine CPP in Sprague Dawley rats. We found that systemic or intrahippocampal
      infused DMSO vehicle (DMSO 20% in saline) 30 min before daily morphine (10 mg/kg,
      s.c.) conditioning did not affect the formation of morphine CPP. In contrast,
      systemic administration (5 mg/kg, s.c.) or intrahippocampal infusion (0, 0.1,
      1.0, 10, 20 microg per side) of the GR antagonist RU38486 blocked or impaired the
      formation of CPP in a dose-dependent manner, respectively. Furthermore, intra-NAc
      infused RU38486 (10 microg per side) but not DMSO vehicle also prevented the
      formation of CPP. These results demonstrate that both the GRs of hippocampus and
      NAc are necessary for the formation of morphine CPP, suggesting a neural network
      function of the GRs in forming the opiate-associated memory.

PMID- 16897721
TI  - Molecular studies on the protective effect of nicotine in adult-onset
      hypothyroidism-induced impairment of long-term potentiation.
AB  - We have recently shown that chronic nicotine treatment reverses hypothyroidism
      induced learning and memory impairment. Chronic nicotine treatment also reverses
      the hypothyroidism-induced impairment of long-term potentiation (LTP). Analysis
      of LTP associated key signaling molecules revealed that chronic nicotine
      treatment prevented the hypothyroidism-induced reduction of the basal
      phosphotransferase activity of CaMKII and protein levels of P-CaMKII. In
      addition, the failure of high frequency stimulation to increase the levels of P
      CaMKII in hypothyroid rats was reversed by nicotine treatment, suggesting that
      the neuroprotective effect of nicotine during hypothyroidism involved activation
      of CaMKII. Furthermore, chronic nicotine treatment reverses the hypothyroidism
      induced elevated phosphatase activity and protein levels of calcineurin, a
      phosphatase that regulates CaMKII activation. We conclude that the
      neuroprotective effects of nicotine in adult-onset hypothyroidism may result from
      restoration of CaMKII and calcineurin activity.

PMID- 16897722
TI  - Subiculum network excitability is increased in a rodent model of temporal lobe
      epilepsy.
AB  - In this study, we used in vitro electrophysiology along with immunohistochemistry
      and molecular techniques to study the subiculum--a limbic structure that gates
      the information flow from and to the hippocampus--in pilocarpine-treated
      epileptic rats. Comparative data were obtained from age-matched nonepileptic
      controls (NEC). Subicular neurons in hippocampal-entorhinal cortex (EC) slices of
      epileptic rats were: (i) hyperexcitable when activated by CA1 or EC inputs; and
      (ii) generated spontaneous postsynaptic potentials at higher frequencies than NEC
      cells. Analysis of pharmacologically isolated, GABA(A) receptor-mediated
      inhibitory postsynaptic potentials revealed more positive reversal potentials in
      epileptic tissue (-67.8 +/- 6.3 mV, n = 16 vs. -74.8 +/- 3.6 mV in NEC, n = 13; P
      < 0.001) combined with a reduction in peak conductance (17.6 +/- 11.3 nS vs. 41.1
      +/- 26.7 nS in NEC; P < 0.003). These electrophysiological data correlated in the
      epileptic subiculum with (i) reduced levels of mRNA expression and
      immunoreactivity of the neuron-specific potassium-chloride cotransporter 2; (ii)
      decreased number of parvalbumin-positive cells; and (iii) increased synaptophysin
      (a putative marker of sprouting) immunoreactivity. These findings identify an
      increase in network excitability within the subiculum of pilocarpine-treated,
      epileptic rats and point at a reduction in inhibition as an underlying mechanism.

PMID- 16897723
TI  - 3-Nitropropionic acid toxicity in hippocampus: protection through N-methyl-D
      aspartate receptor antagonism.
AB  - The over-activation of glutamate receptors can lead to excitotoxic cell death and
      is believed to be involved in the progression of neurodegenerative events in the
      vulnerable hippocampus. Here, we used an in vitro slice model to study toxicity
      produced in the hippocampus by the mitochondrial toxin 3-nitropropionic acid (3
      NP). The organotypic slice cultures exhibit native cellular organization as well
      as dense arborization of neuronal processes and synaptic contacts. The
      hippocampal slices were exposed to 3-NP for 2-20 days, causing calpain-mediated
      breakdown of the spectrin cytoskeleton, a loss of pre- and postsynaptic markers,
      and neuronal atrophy. The N-methyl-D-aspartate (NMDA) receptor antagonist
      memantine reduced both the cytoskeletal damage and synaptic decline in a dose
      dependent manner. 3-NP-induced cytotoxicity, as determined by the release of
      lactate dehydrogenase, was also reduced by memantine with EC50 values from 1.7 to
      2.3 microM. Propidium iodide fluorescence and phase contrast microscopy confirmed
      memantine neuroprotection against the chronic toxin exposure. In addition, the
      protected tissue exhibited normal neuronal morphology in the major hippocampal
      subfields. These results indicate that antagonists of NMDA-type glutamate
      receptors are protective during the toxic outcome associated with mitochondrial
      dysfunction. They also provide further evidence of memantine's therapeutic
      potential against neurodegenerative diseases.

PMID- 16897724
TI  - Hippocampal place cells, context, and episodic memory.
AB  - Although most observers agree that the hippocampus has a critical role in
      learning and memory, there remains considerable debate about the precise
      functional contribution of the hippocampus to these processes. Two of the most
      influential accounts hold that the primary function of the hippocampus is to
      generate cognitive maps and to mediate episodic memory processes. The well
      documented spatial firing patterns (place fields) of hippocampal neurons in
      rodents, along with the spatial learning impairments observed with hippocampal
      damage support the cognitive mapping hypothesis. The amnesia for personally
      experienced events seen in humans with hippocampal damage and the data of animal
      models, which show severe memory deficits associated with hippocampal lesions,
      support the episodic memory account. Although an extensive literature supports
      each of these hypotheses, a specific contribution of place cells to episodic
      memory has not been clearly demonstrated. Recent data from our laboratory,
      together with previous findings, indicate that hippocampal place fields and
      neuronal responses to task-relevant stimuli are highly sensitive to the context,
      even when the contexts are defined by abstract task demands rather than the
      spatial geometry of the environment. On the basis of these findings, it is
      proposed that place fields reflect a more general context processing function of
      the hippocampus. Hippocampal context representations could serve to differentiate
      contexts and prime the relevant memories and behaviors. Since episodic memories,
      by definition, include information about the time and place where the episode
      occurred, contextual information is a necessary prerequisite for any episodic
      memory. Thus, place fields contribute importantly to episodic memory as part of
      the needed context representations. Additionally, recent findings indicate that
      hippocampal neurons differentiate contexts at progressively finer levels of
      detail, suggesting a hierarchical coding scheme which, if combined with temporal
      information, could provide a means of differentiating memory episodes.

PMID- 16897725
TI  - Modulatory effects of dextran sulfate and fucoidan on binding and channel
      properties of AMPA receptors isolated from rat brain.
AB  - Previous work showed that the glycosaminoglycan (GAG) dextran sulfate (500 kDa)
      altered the binding and channel properties of alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid (AMPA)-type glutamate receptors. The current study
      compared the effects of dextran sulfate with another GAG, fucoidan (100-180 kDa),
      to determine whether GAG-mediated changes in high-affinity binding of AMPA
      receptors have a concomitant influence on specific channel properties. Dextran
      sulfate was more potent in inhibiting high-affinity AMPA binding to solubilized
      receptors (EC(50) of 7 nM) compared to fucoidan (EC(50) of 124 nM). Similarly,
      dextran sulfate was more potent in modulating the channel properties of purified
      and reconstituted AMPA receptors. Dextran sulfate, at 1 mug/ml (2 nM), produced a
      three to fourfold increase in open channel probability and a threefold increase
      in mean burst duration of channel activity elicited by 283 nM AMPA. The mean open
      time was increased by two to threefold and closed times were decreased by two to
      eightfold. Fucoidan produced similar effects at a concentration many times higher
      than that of dextran sulfate. Dextran sulfate and fucoidan had no effect on the
      single channel conductance or the ability of a specific antagonist to block AMPA
      channels. The effects of GAGs on multichannel patches showed an interactive
      channel gating behavior resulting in macroscopic currents with long lived open
      channel life times. These findings suggest that GAG components of proteoglycans
      can interact with and alter the binding affinity of AMPA receptors and modulate
      their functional properties.

PMID- 16897727
TI  - Kinetic analysis of developmental changes in vesicular monoamine transporter-2
      function.
AB  - The vesicular monoamine transporter-2 (VMAT-2) sequesters cytoplasmic dopamine
      (DA) into vesicles and may thus protect neurons from DA-associated oxidative
      damage. VMAT-2 function, as assessed by measuring [(3)H]DA uptake, is less in
      adolescent when compared with young adult rats and VMAT-2 susceptibility to
      methamphetamine also changes with age. Thus, developmental alterations in VMAT-2
      function warrant further investigation. The current study extends these findings
      by showing that the initial velocities of both DA uptake and methamphetamine
      induced DA efflux are less in adolescent postnatal day (PND 38-42) vs. young
      adult (PND 88-92) rats as assessed in nonmembrane associated (presumably
      cytoplasmic) vesicles purified from rat striatal synaptosomes. The decrease in DA
      uptake velocities is due to a decrease in the V(max) of DA uptake with no change
      in the K(m). The density of kinetically active VMAT-2 and VMAT-2 immunoreactivity
      are less in adolescent vs. young adult rats while both the turnover number (2.4
      2.8 s(-) (1)) and rate constant for the association of DA with VMAT-2 ( 1 x 10(7)
      M(-) (1) s(-) (1)) are similar in these age groups. These results suggest that
      the kinetics of DA binding and translocation across the membrane are unaltered in
      the vesicles of PND 38-42 vs. PND 88-92 rats. However, decreased VMAT-2 density
      in PND 38-42 rats reduces V(max), which in turn lowers DA uptake.

PMID- 16897726
TI  - Escalating dose pretreatment induces pharmacodynamic and not pharmacokinetic
      tolerance to a subsequent high-dose methamphetamine binge.
AB  - A major feature of human methamphetamine (METH) abuse is the gradual dose
      escalation that precedes high-dose exposure. The period of escalating doses (EDs)
      is likely associated with development of tolerance to aspects of METH's
      pharmacologic and toxic effects but the relative contributions of pharmacokinetic
      and pharmacodynamic factors have not been well defined. In our prior studies in
      rats, we showed that pretreatment with an ED-METH regimen (0.1-4.0 mg/kg over 14
      days) attenuated the toxicity of a subsequently administered high-dose METH binge
      (4 x 6 mg/kg at 2 h interval) that itself produced behavioral stereotypy,
      increases in core temperature, and decreases in DA system phenotypic markers in
      caudate-putamen (CP). Using those ED-METH and binge protocols in the present
      studies, pharmacokinetic and pharmacodynamic parameters that may have contributed
      to the apparent neuroprotection afforded by ED-METH were assessed. The ED-METH
      regimen itself reduced [(3)H]WIN35,428 (WIN) binding to the dopamine transporter
      (DAT) by 15% in CP, but did not affect DA content. During the METH binge, ED-METH
      pretreated animals showed attenuated increases in core temperature while
      concurrent microdialysis studies in CP showed a reduced DA response despite
      unaltered extracellular levels of METH. At 1 h after the binge, concentrations of
      METH and its metabolite amphetamine in brain and plasma were unaffected by the ED
      METH. The results show that ED-METH pretreatment produces reductions in DAT
      binding and the DA response during a subsequent METH binge by altering
      pharmacodynamic and not pharmacokinetic parameters.

PMID- 16897728
TI  - Selective detection and transport of fully matched DNA by DNA-loaded microtubule
      and kinesin motor protein.
AB  - DNA-loaded microtubules (MTs) moving on a kinesin motor protein-coated substrate
      can selectively hybridize with a target fully matched DNA over single-base
      mismatched DNA and transport it. This technique is capable of collecting target
      biomolecules toward one point site to design new methodology of DNA analysis.

PMID- 16897729
TI  - Auto-antibodies in prostate cancer: humoral immune response to antigenic
      determinants coded by the differentially expressed transcripts FLJ23438 and
      VAMP3.
AB  - BACKGROUND: Here we evaluate auto-antibody response against two potential
      antigenic determinants of genes highly expressed in low Gleason Score prostate
      cancer (PC) tumor samples, namely FLJ23438 and VAMP3. METHODS: RT-PCR assays were
      used to analyze mRNA expression profiles of FLJ23438 and VAMP3 transcripts. The
      auto-antibody response against FLJ23438 and VAMP3 recombinant proteins was tested
      by immunoblot assays using PC, benign prostate hyperplasia (BPH), healthy donors
      (HD), and other human cancers plasma samples. RESULTS: Our data showed that 37%
      (10/27) and 7.4% (2/27) of PC plasma samples presented auto-antibodies against
      FLJ23438 and VAMP3, respectively. Only 8.3% (1/12) of BPH plasma samples were
      reactive for both auto-antibodies, while none (0/12) of HD plasma samples tested
      were reactive. CONCLUSIONS: The prevalence of 37% of positive PC plasma samples
      for anti-FLJ23438 antibodies suggests that humoral immune response against this
      antigenic determinant could be a potential serum marker for this cancer.

PMID- 16897730
TI  - Reorganization of mouse sperm lipid rafts by capacitation.
AB  - One of the hallmarks of mammalian sperm capacitation is the loss of cholesterol
      from the plasma membrane. Cholesterol has been associated with the formation of
      detergent insoluble membrane microdomains in many cell types, and sperm from
      several mammalian species have been shown to contain detergent-resistant
      membranes (DRMs). The change in cholesterol composition of the sperm plasma
      membrane during capacitation raises the question of whether the contents of DRMs
      are altered during this process. In this study, we investigated changes in
      protein composition of DRMs isolated from uncapacitated or capacitated mouse
      sperm. TX-100 insoluble membranes were fractionated by sucrose flotation gradient
      centrifugation and analyzed by Western and lectin blotting, and capacitation
      related differences in protein composition were identified. Following
      capacitation, the detergent insoluble fractions moved to lighter positions on the
      sucrose gradients, reflecting a global change in density or composition. We
      identified several individual proteins that either became enriched or depleted in
      DRM fractions following capacitation. These data suggest that the physiological
      changes in sperm motility, ability to penetrate the zona pellucida (ZP), ZP
      responsiveness, and other capacitation-dependent changes, may be due in part to a
      functional reorganization of plasma membrane microdomains.

PMID- 16897731
TI  - Production of enzymatically active ketosteroid isomerase following insoluble
      expression in Escherichia coli.
AB  - Enzymatically active Delta(5)-3-ketosteroid isomerase (KSI) protein with a C
      terminus his(6)-tag was produced following insoluble expression using Escherichia
      coli. A simple, integrated process was used to extract and purify the target
      protein. Chemical extraction was shown to be as effective as homogenization at
      releasing the inclusion body proteins from the bacterial cells, with complete
      release taking less than 20 min. An expanded bed adsorption (EBA) column
      utilizing immobilized metal affinity chromatography (IMAC) was then used to
      purify the denatured KSI-(His(6)) protein directly from the chemical extract.
      This integrated process greatly simplifies the recovery and purification of
      inclusion body proteins by removing the need for mechanical cell disruption,
      repeated inclusion body centrifugation, and difficult clarification operations.
      The integrated chemical extraction and EBA process achieved a very high purity
      (99%) and recovery (89%) of the KSI-(His(6)), with efficient utilization of the
      adsorbent matrix (9.74 mg KSI-(His(6))/mL adsorbent). Following purification the
      protein was refolded by dilution to obtain the biologically active protein.
      Seventy-nine percent of the expressed KSI-(His(6)) protein was recovered as
      enzymatically active protein with the described extraction, purification, and
      refolding process. In addition to demonstrating the operation of this intensified
      inclusion body process, a plate-based concentration assay detecting KSI-(His(6))
      is validated. The intensified process in this work requires minimal optimization
      for recovering novel his-tagged proteins, and further improves the economic
      advantage of E. coli as a host organism.

PMID- 16897732
TI  - Gene expression profiles of vitrified in vivo derived 8-cell stage mouse embryos
      detected by high density oligonucleotide microarrays.
AB  - Very little is known about the effect of vitrification on gene functions after
      warming. The goals of our study were to compare the gene expression patterns, and
      identify those most affected. For this, 8-cell stage embryos were collected from
      ICR mice and vitrified with solid surface vitrification technique, while
      maintaining equal numbers of embryos as control. Total RNAs were extracted and
      two rounds of amplification were employed. Finally three micrograms of
      contrasting RNA samples were hybridized on the Agilent Mouse 22 K oligonucleotide
      slides and the results were analyzed with subsequent verification by independent
      real-time PCR analyses. The two rounds of amplification with 5 ng tRNA input have
      yielded 15-16 microg of cRNA. The analyses of repeated hybridizations showed
      20,183 genes/ESTs as common signatures, and unsupervised analysis identified 628
      differentially expressed (P < 0.01) genes. However, with at least 1.5-fold change
      considerations, 183 genes were differentially expressed (P < 0.01) out of which
      107 were upregulated. The independent analysis with real-time PCR and unamplified
      samples fully confirmed the results of microarray, indicating the linearity of
      amplification. Furthermore, this novel gene expression study for vitrified
      embryos identified many new candidate genes with overrepresentation in some
      important biological processes. Thus, it is possible to conclude that the
      expression pattern reflected a broad spectrum of consequences of vitrification on
      embryos, with most effects on metabolism, regulatory role and stress response
      genes and allowed the identification of new candidate marker genes for
      cryosurvival.

PMID- 16897733
TI  - Wechsler Adult Intelligence Scale-III inter-subtest scatter: a comparison of
      brain-damaged patients and normal controls.
AB  - This study assessed the validity of Wechsler Adult Intelligence Scale-Third
      Edition (WAIS-III) inter-subtest scatter (as measured by the scaled score range)
      as an indication of cognitive impairment due to brain dysfunction. Participants
      were 174 individuals with documented brain damage. Means for age, education, and
      WAIS-III full-scale IQ were 49.19 years (SD = 15.33), 12.57 years, (SD = 2.78),
      and 88.45 (SD = 17.78). The scatter ranges for brain-damaged participants were
      compared with those of the WAIS-III standardization sample. Results indicated
      that the full-scale IQ is significantly correlated with amount of scatter, r(172)
      = .42, p < .0001, so that a definitive answer to the question requires control of
      full-scale IQ. In the present analyses, inter-subtest scatter among the
      individuals for the sample as a whole was no greater than that for persons in the
      standardization sample, but subtest scatter was significantly greater for
      participants with IQs > or = 90. This finding suggests that there may be small
      differences in scatter between brain-damaged persons and normal controls, but
      that scatter is relatively insensitive to the presence of brain damage or
      dysfunction. Therefore, interpretation of marked inter-subtest variability as a
      sign of brain damage appears unwarranted.

PMID- 16897734
TI  - Development and evaluation of new factor scales for the Expectations About
      Counseling Inventory in a college sample.
AB  - Given the lack of agreement over the factor structure and scoring system used
      with the Expectations About Counseling Inventory (EAC-B), the primary purpose of
      this investigation was to reevaluate the factor structure of the EAC-B and to
      construct factor scales based on that structure. After constructing these scales,
      the second objective was to evaluate the relationships among expectations about
      counseling, the five-factor model of personality (FFM), and gender-related
      variables. The responses of 460 undergraduate students to all 66 items on the EAC
      B suggested three factors: facilitative conditions, counselor expertise, and
      client involvement. Expectations for facilitative conditions were positively
      correlated with extraversion, agreeableness, conscientiousness, masculinity, and
      femininity; expectations for counselor expertise were negatively correlated with
      openness and agreeableness and positively correlated with masculinity; and
      expectations for client involvement were positively correlated with extraversion,
      openness, agreeableness, conscientiousness, and femininity. Femininity was the
      strongest predictor of the facilitative conditions and client involvement scales
      when the effects of all the other variables were partialled out, whereas openness
      to experience and gender were the best predictors of counselor expertise when the
      effects of all the other variables were partialled out.

PMID- 16897736
TI  - Personality pathology and its relation to couple functioning.
AB  - The study aimed at understanding the relationship between personality pathology
      and couple functioning, both in terms of general functioning and communication
      specifically, in a sample of 146 psychiatric outpatients. The results indicated
      that couple communication was best predicted by a combination of the symptoms
      within each of the three personality disorder clusters and the total number of
      personality disorder symptoms while general family functioning was best predicted
      by the total number of Axis I disorders. No demographic variables were found to
      be related to the level of couple functioning. Future research needs to focus on
      understanding what makes it difficult for people with personality disorder traits
      to function in relationships.

PMID- 16897735
TI  - Stages of change as a correlate of mental health symptoms in abused, low-income
      African American women.
AB  - The current study aims to further our understanding of the applicability of the
      transtheoretical model (TM) to intimate partner violence (IPV), with particular
      focus on mental health symptoms (depression, posttraumatic stress disorder
      symptomatology, suicidal ideation) in a sample of low-income African American
      women seeking medical services at an inner city emergency department. Results
      revealed that of the 121 abused African American women, the majority (95%) were
      in the precontemplation and contemplation stages of the change process. Further,
      contrary to predictions, bivariate analyses revealed those at further stages of
      change endorsed more severe mental health symptoms. However, a multivariate
      analysis of variance examining differences in level of mental health symptoms
      between women high and low on stages of change was inconclusive due to the small
      number of women at the higher stages of the TM model. These findings contribute
      to the growing body of literature supporting the TM as applied to IPV. Results
      are discussed in terms of applicability to intervention design.

PMID- 16897738
TI  - Efficient adenoviral-mediated gene delivery into porcine mesenchymal stem cells.
AB  - Mesenchymal stem cell (MSC) mediated gene therapy research has been conducted
      predominantly on rodents. Appropriate large animal models may provide additional
      safety and efficacy information prior to human clinical trials. The objectives of
      this study were: (a) to optimize adenoviral transduction efficiency of porcine
      bone marrow MSCs using a commercial polyamine-based transfection reagent
      (GeneJammer, Stratagene, La Jolla, CA), and (b) to determine whether transduced
      MSCs retain the ability to differentiate into mesodermal lineages. Porcine MSCs
      (pMSCs) were infected under varying conditions, with replication-defective
      adenoviral vectors carrying the GFP gene and GFP expression analyzed. Transduced
      cells were induced to differentiate in vitro into adipogenic, chondrogenic, and
      osteogenic lineages. We observed a 5.5-fold increase in the percentage of GFP
      expressing pMSCs when adenovirus type 5 carrying the adenovirus type 35 fiber
      (Ad5F35eGFP) was used in conjunction with GeneJammer. Transduction of pMSCs at
      10.3-13.8 MOI (1,500-2,000 vp/cell) in the presence of Gene Jammer yielded the
      highest percentage of GFP-expressing cells ( approximately 90%) without affecting
      cell viability. A similar positive effect was detected when pMSCs were infected
      with an Ad5eGFP vector. Presence of fetal bovine serum (FBS) during adenoviral
      transduction enhanced vector-encoded transgene expression in both GeneJammer
      treated and control groups. pMSCs transduced with adenovirus vector in the
      presence of GeneJammer underwent lipogenic, chondrogenic, and osteogenic
      differentiation. Addition of GeneJammer during adenoviral infection of pMSCs can
      revert the poor transduction efficiency of pMSCs while retaining their
      pluripotent differentiation capacity. GeneJammer-enhanced transduction will
      facilitate the use of adenoviral vectors in MSC-mediated gene therapy models and
      therapies.

PMID- 16897737
TI  - Mapping and partial characterization of proteases expressed by a CHO production
      cell line.
AB  - The proteolytic activities expressed by a Chinese hamster ovary (CHO) cell line
      in the cultivation supernatant during the production of recombinant factor VIII
      were mapped with a broad spectrum protease assay and a series of different types
      of protease inhibitors. The destabilizing effect on the product emanated from a
      metalloproteinase, which could be effectively blocked by chelating agents to lead
      to product stabilization. Amino acid sequences of the isolated metalloproteinase
      were found to have sequence homology with matrix metalloproteinases (MMPs) MMP3,
      MMP10, and MMP12. Several species with metalloproteinase activity were
      characterized and found to be related to each other. The results indicate that an
      MMP pro-enzyme of >/=200 kDa was released from the CHO cells during the
      production phase. The enzyme expressed collagenase/gelatinase activity when
      activated. Due to autoproteolysis, a number of smaller, less specific MMPs were
      formed with the smallest form, a 19.4 kDa protein, being the most active. These
      results may be of particular relevance for other production processes using CHO
      cells for the expression of recombinant proteins.

PMID- 16897740
TI  - An exclusion mechanism in ion exchange chromatography.
AB  - Protein dynamic binding capacities on ion exchange resins are typically expected
      to decrease with increasing conductivity and decreasing protein charge. There
      are, however, conditions where capacity increases with increasing conductivity
      and decreasing protein charge. Capacity measurements on two different commercial
      ion exchange resins with three different monoclonal antibodies at various pH and
      conductivities exhibited two domains. In the first domain, the capacity
      unexpectedly increased with increasing conductivity and decreasing protein
      charge. The second domain exhibited traditional behavior. A mechanism to explain
      the first domain is postulated; proteins initially bind to the outer pore regions
      and electrostatically hinder subsequent protein transport. Such a mechanism is
      supported by protein capacity and confocal microscopy studies whose results
      suggest how knowledge of the two types of IEX behavior can be leveraged in
      optimizing resins and processes.

PMID- 16897741
TI  - Genetic inactivation of the APC gene contributes to the malignant progression of
      sporadic hepatocellular carcinoma: a case report.
AB  - Although activated Wnt/beta-catenin pathway is considered to be one of the main
      driving forces of hepatocarcinogenesis, no somatic mutations of the adenomatous
      polyposis coli (APC) gene have been found in sporadic hepatocellular carcinoma
      (HCC) to date. Here we present a case of a sporadic nodule-in-nodule-type HCC
      that provides the first evidence that biallelic genetic inactivation of the APC
      gene contributed to the development of the tumor. High-density array-based
      comparative genomic hybridization (aCGH) was performed to clarify genome-wide
      chromosomal structural alteration profiles of both early and advanced components
      of this nodule-in-nodule HCC. aCGH analysis revealed a chromosomal loss of the
      APC gene locus only in the inner advanced component of this tumor. Direct
      sequencing of the remaining allele revealed a nonsense mutation at codon 682 in
      the Armadillo repeats, resulting in a truncated protein that lacked all of the
      beta-catenin-binding motifs. Nonsense mutations at this location are rare among
      other types of cancer. In conclusion, combined with an immunohistochemical
      analysis of the beta-catenin protein, this case provides the first evidence that
      genetic inactivation of the APC gene can play a significant role in the
      progression of sporadic HCC, probably by activating the Wnt/beta-catenin pathway.

PMID- 16897743
TI  - Copy-number methods dramatically underestimate loss of heterozygosity in cancer.

PMID- 16897742
TI  - Molecular dissection of t(11;17) in acute myeloid leukemia reveals a variety of
      gene fusions with heterogeneous fusion transcripts and multiple splice variants.
AB  - The majority of translocations that involve the long arms of chromosomes 11 and
      17 in acute myeloid leukemia appear identical on the cytogenetic level.
      Nevertheless, they are diverse on the molecular level. At present, two genes are
      known in 11q23 and four in 17q12-25 that generate five distinct fusion genes: MLL
      MLLT6/AF17, MLL-LASP1, MLL-ACACA or MLL-SEPT9/MSF, and ZBTB16/PLZF-RARA. We
      analyzed 14 cases with a t(11;17) by fluorescence in situ hybridization and
      molecular genetic techniques and determined the molecular characteristics of
      their fusion genes. We identified six different gene fusions that comprised seven
      cases with a MLL-MLLT6/AF17, three with a MLL-SEPT9/MSF, and one each with MLL
      LASP1, MLL-ACACA, and ZBTB16/PLZF-RARA fusions. In the remaining case, a MLL
      SEPT6/Xq24 fusion suggested a complex rearrangement. The MLL-MLLT6/AF17
      transcripts were extremely heterogeneous and the detection of seven different in
      frame transcript and splice variants enabled us to predict the protein domains
      relevant for leukemogenesis. The putative MLL-MLLT6 consensus chimeric protein
      consists of the AT-hook DNA-binding, the methyltransferase, and the CXXC zinc
      finger domains of MLL and the highly conserved octapeptide and the leucine-zipper
      dimerization motifs of MLLT6. The MLL-SEPT9 transcripts showed a similar high
      degree of variability. These analyses prove that the diverse types of t(11;17)
      associated fusion genes can be reliably identified and delineated with a proper
      combination of cytogenetic and molecular genetic techniques. The heterogeneity of
      transcripts encountered in cases with MLL-MLLT6/AF17 and MLL-SEPT9/MSF fusions
      clearly demonstrates that thorough attention has to be paid to the appropriate
      selection of primers to cover all these hitherto unrecognized fusion variants.

PMID- 16897744
TI  - Imbalances of chromosome arm 1p in pediatric and adult germ cell tumors are
      caused by true allelic loss: a combined comparative genomic hybridization and
      microsatellite analysis.
AB  - Previous studies on childhood germ cell tumors (GCTs) report highly variable
      frequencies of losses at chromosome arm 1p. Since deletions at 1p portend a poor
      prognosis in other embryonal tumors, this study aims to clarify the question of
      the frequency of true allelic loss at 1p and whether it constitutes a prognostic
      parameter. We analyzed 13 GCTs from different gonadal and extragonadal sites of
      children (4 teratomas, 9 malignant GCTs) and 18 GCTs of adolescents and adults (3
      teratomas; 15 malignant GCTs) using automated microsatellite analysis with 23
      polymorphic markers and chromosomal "high resolution" comparative genomic
      hybridization (HR-CGH). With this combined approach, we detected loss of
      heterozygosity (LOH) at 1p in 8/9 childhood malignant GCTs with concordant data
      from HR-CGH and microsatellite analyses. In contrast, LOH at 1p was not detected
      in childhood teratomas (0/4) and constituted a rare event in GCTs of adolescence
      and adulthood (3/18). The commonly deleted region was located at distal 1p36
      pter, with a proximal boundary between the markers D1S450 and D1S2870. These data
      unequivocally demonstrate that deletion at 1p is common in childhood GCTs and
      results in allelic loss. This observation argues for the presence of a classical
      tumor suppressor at distal 1p. Considering the high frequency of LOH at 1p and
      the overall favorable prognosis of childhood GCTs, a prognostic impact of LOH at
      1p in childhood GCTs appears unlikely. However, since two postpubertal tumors
      with LOH at 1p progressed, a prognostic relevance in this age group seems
      possible, warranting a prospective evaluation.

PMID- 16897745
TI  - Derivation and characterization of cholesterol-independent non-GS NS0 cell lines
      for production of recombinant antibodies.
AB  - Presented is an antibody production platform based on the fed-batch culture of
      recombinant NS0-derived cell lines. NS0 host cells, obtained from the European
      Collection of Cell Cultures (ECACC, Salisbury, UK, Part No. 85110503), were first
      adapted to grow in a protein-free, cholesterol-free medium. The resulting host
      cell line was designated NS0-PFCF (protein-free, cholesterol-free). The five
      production cell lines presented here were generated using a common protocol
      consisting of transfection by electroporation and subcloning. The NS0-PFCF host
      cell line was transfected using a single expression vector containing the
      Escherichia coli xanthine-guanine phosphoribosyl transferase gene (gpt), and the
      antibody heavy and light chain genes driven by the CMV promoter. The five cell
      lines were chosen after one to three rounds of iterative subcloning, which
      resulted in a 19-64% increase in antibody productivity when four mother-daughter
      cell pairs were cultured in a fed-batch bioreactor process. The production cell
      lines were genetically characterized to determine antibody gene integrity,
      nucleotide sequences, copy number, and the number of insertion sites in the NS0
      cell genome. Genetic characterization data indicate that each of the five
      production cell lines has a single stably integrated copy of the antibody
      expression vector, and that the antibody genes are correctly expressed. Stability
      of antibody production was evaluated for three of the five cell lines by
      comparing the early stage seed bank with the Working Cell Bank (WCB). Antibody
      productivity was shown to be stable in two of three cell lines evaluated, while
      one of the cell lines exhibited a 20% drop in productivity after passaging for
      approximately 4 weeks. These five NS0-derived production cell lines were
      successfully cultured to produce antibodies with acceptable product quality
      attributes in a standardized fed-batch bioreactor process, consistently achieving
      an average specific productivity of 20-60 pg/cell-day, and a volumetric
      productivity exceeding 120 mg/L-day (Burky et al., 2006). In contrast to the
      commonly available NS0 host cell line, which requires serum and cholesterol for
      growth, and the commonly used expression vector system, which uses a proprietary
      glutamine synthetase selection marker (GS-NS0), these NS0 cells are cholesterol
      independent, grow well in a protein-free medium, use a non-proprietary selection
      marker, and do not require gene amplification for productivity improvement. These
      characteristics are advantageous for use of this NS0 cell line platform for
      manufacturing therapeutic antibodies.

PMID- 16897746
TI  - Distinct patterns of DNA copy number alteration are associated with different
      clinicopathological features and gene-expression subtypes of breast cancer.
AB  - Breast cancer is a leading cause of cancer-death among women, where the
      clinicopathological features of tumors are used to prognosticate and guide
      therapy. DNA copy number alterations (CNAs), which occur frequently in breast
      cancer and define key pathogenetic events, are also potentially useful prognostic
      or predictive factors. Here, we report a genome-wide array-based comparative
      genomic hybridization (array CGH) survey of CNAs in 89 breast tumors from a
      patient cohort with locally advanced disease. Statistical analysis links distinct
      cytoband loci harboring CNAs to specific clinicopathological parameters,
      including tumor grade, estrogen receptor status, presence of TP53 mutation, and
      overall survival. Notably, distinct spectra of CNAs also underlie the different
      subtypes of breast cancer recently defined by expression-profiling, implying
      these subtypes develop along distinct genetic pathways. In addition, higher
      numbers of gains/losses are associated with the "basal-like" tumor subtype, while
      high-level DNA amplification is more frequent in "luminal-B" subtype tumors,
      suggesting also that distinct mechanisms of genomic instability might underlie
      their pathogenesis. The identified CNAs may provide a basis for improved patient
      prognostication, as well as a starting point to define important genes to further
      our understanding of the pathobiology of breast cancer. This article contains
      Supplementary Material available at http://www.interscience.wiley.com/jpages/1045
      2257/suppmat

PMID- 16897748
TI  - Genomic alterations in lobular neoplasia: a microarray comparative genomic
      hybridization signature for early neoplastic proliferationin the breast.
AB  - The identification of genomic alterations occurring in neoplastic lesions
      provides insight into both lesion occurrence and disease progression. In this
      study, we used microarray comparative genomic hybridization (CGH) to investigate
      genetic changes in atypical lobular hyperplasia (ALH) and lobular carcinoma in
      situ (LCIS), as the presence of these lobular neoplastic lesions is an indicator
      of risk in the development of invasive breast cancer. DNA was extracted from
      microdissected archival breast tissue containing ALH or LCIS, lacking adjacent
      invasive carcinoma, and subjected to whole-genome tiling path microarray-CGH
      using the submegabase resolution tiling set (SMRT)-array platform. Twelve ALH and
      13 LCIS lesions were examined. Copy number alterations were identified using
      statistical criteria and validated with Real-Time PCR and fluorescence in situ
      hybridization. From statistical analysis, a greater number of alterations were
      observed in ALH compared to LCIS. Alterations common to ALH include gain at
      2p11.2 and loss at 7p11-p11.1 and 22q11.1. Alterations common to LCIS include
      gain at 20q13.13 and loss at 19q13.2-q13.31. In both ALH and LCIS, we observed
      loss of 16q21-q23.1, an altered region previously identified in lobular neoplasia
      and invasive carcinoma. The validation of select alterations reinforces the
      genomic signature. This study represents the first whole-genome investigation of
      lobular neoplastic breast lesions using clinical archival specimens. The
      identified genomic signature includes copy number alterations not previously
      identified for lobular neoplasia. This genomic signature, common to ALH and LCIS,
      suggests a role for the acquisition of novel genomic alterations in the aberrant
      cellular proliferation that defines lobular neoplasia.

PMID- 16897747
TI  - Comprehensive assessment of DNA copy number alterations in human prostate cancers
      using Affymetrix 100K SNP mapping array.
AB  - Although multiple recurrent chromosomal alterations have been identified in
      prostate cancer cells, the specific genes driving the apparent selection of these
      changes remain largely unknown. In part, this uncertainty is due to the limited
      resolution of the techniques used to detect these alterations. In this study, we
      applied a high-resolution genome-wide method, Affymetrix 100K SNP mapping array,
      to screen for somatic DNA copy number (CN) alterations among 22 pairs of samples
      from primary prostate cancers and matched nonmalignant tissues. We detected 355
      recurrent deletions and 223 recurrent gains, many of which were novel. As
      expected, the sizes of novel alterations tend to be smaller. Importantly, among
      tumors with increasing grade, Gleason sum 6, 7, and 8, we found a significant
      trend of larger number of alterations in the tumors with higher grade. Overall,
      gains are significantly more likely to occur within genes (74%) than are
      deletions (49%). However, when we looked at the most frequent CN alterations,
      defined as those in > or =4 subjects, we observed that both gains (85%) and
      deletions (57%) occur preferentially within genes. An example of a novel,
      recurrent alteration observed in this study was a deletion between the ERG and
      TMPRSS2 genes on chromosome 21, presumably related to the recently identified
      fusion transcripts from these two genes. Results from this study provide a basis
      for a systematic and comprehensive cataloging of CN alterations associated with
      grades of prostate cancer, and the subsequent identification of specific genes
      that associated with initiation and progression of the disease. This article
      contains supplementary material available via the Internet at
      http://www.interscience.wiley.com/jpages/1045-2257/suppmat

PMID- 16897750
TI  - Abnormal urethral motor function is common in female stress, mixed, and urge
      incontinence.
AB  - AIM: To investigate the urethral motor function in incontinent women. MATERIALS
      AND METHODS: The intraurethral pressure was measured continuously in the high
      pressure zone of the urethra at rest and during repeated short squeezes around
      the microtip transducer catheter in a group of 205 women with clinically manifest
      urinary incontinence (severe), and compared with the findings of investigations
      in 87 middle-aged women (53-63 years) with treatment naive incontinence (mild-to
      moderate) and healthy controls. RESULTS: Women with established incontinence
      significantly (P < 0.001) more often (66%) had a pressure fall during or
      immediately following squeeze than women with treatment naive incontinence (35%)
      or asymptomatic women (25%). The acceleration of urinary flow and the maximal
      flow rate were significantly (P < 0.01) increased in patients with incontinence:
      acceleration was 13 +/- 2.2 (17.8), 20 +/- 2.8 (18.9), and 32 +/- 4.9 (24.9)
      degrees (mean +/- SEM; SD) for incontinence, naive incontinence and no
      incontinence, respectively; maximum urinary flow rate was 23, 22, and 16 ml/sec.
      No statistical differences in any of these measures were seen when stress and
      urge incontinence were compared. CONCLUSION: Women with stress, urge, and mixed
      urinary incontinence seem to have a primary neuromuscular disorder in the
      urethra, which presents itself as an overactive opening mechanism with a urethral
      pressure fall instead of a pressure increase on provocation during the filling
      phase of the bladder, and during bladder emptying a more efficient opening of the
      bladder outlet than in normal women. We suggest that one and the same
      pathophysiological mechanism participates in female stress, urge, and mixed
      incontinence.

PMID- 16897751
TI  - Transcriptional and proteolytic regulation of the insulin-like growth factor-I
      system of equine articular chondrocytes by recombinant equine interleukin-1beta.
AB  - Interleukin-1 (IL-1) and insulin-like growth factor-I (IGF-I), which have
      opposing effects on matrix metabolism within articular cartilage, are thought to
      play prominent roles in the pathogenesis of osteoarthritis. To better understand
      the link between these anabolic (IGF-I) and catabolic (IL-1) stimuli, we examined
      exogenous IL-1 regulation of the IGF-I signaling system of articular chondrocytes
      (ACs). Equine ACs from non-arthritic stifle joints were expanded in monolayer
      culture, encapsulated for 10 days in alginate beads, and stimulated as high
      density monolayers with recombinant equine IL-1beta (0, 1, 10 ng/ml) for 48 h. IL
      1beta enhanced expression of IGF-IR levels, as determined by both [125I]-IGF-I
      binding studies and Western blotting, while reducing the concentration of
      endogenous IGF-I detected in conditioned media by radioimmunoassay. Western
      ligand blotting revealed that chondrocytes primarily secreted IGF binding
      proteins (IGFBPs) with molecular weights of 28-30 and 32-34 kDa, which were
      identified as IGFBPs 5 and 2, respectively, and that IL-1beta treatment
      diminished IGFBP-2, the prominent homolog in conditioned media. Northern blot
      analysis suggested IL-1beta regulation of IGF-I and, to some extent, IGF-IR was
      mediated by transcription; however, the cytokine did not affect IGFBP-2
      expression. To test for evidence of proteolysis by matrix metalloproteinases
      (MMPs), additional cultures were co-incubated with inhibitors for MMPs 2/9, 3,
      and 8. IGFBP-2 suppression was partially reversed by gelatinase (MMP-2/9)
      inhibition. In summary, these findings further delineate the role of IL-1 as a
      key regulator of the IGF-I system within articular cartilage, demonstrating that
      regulation occurs through both direct (transcriptional) and indirect
      (proteolytic) mechanisms.

PMID- 16897749
TI  - Revisiting reliability of quantified perineal ultrasound: Bland and Altman
      analysis of a new protocol for the rectangular coordinate method.
AB  - AIMS: This study tested the reliability of a new protocol for the rectangular
      coordinate method of quantifying perineal ultrasound. METHODS: Representative
      scans of healthy primiparous females were quantified by positioning a pubic bone
      template, drawn onto an acetate sheet containing x-y axes, over scans, by
      aligning the x-axis with the pubic bone central axis. Values for x (D(x)) and y
      (D(y)) located the urethrovesical junction (UVJ) at Rest, and at maximal Valsalva
      and Kegel. Range of motion (V-K) was calculated. Bland and Altman analysis,
      correlations, and t-tests determined intra- and inter-rater reliability, and
      variance due to designation of the pubic bone central axis (template control).
      RESULTS: Correlations averaged 0.72, 0.70, and 0.92 for intra-rater, inter-rater,
      and template control experiments. D(x) Rest, D(x) Kegel, and V-K were reliable in
      all experiments. First and second measures for inter-rater D(y) Rest and D(y)
      Kegel, and template control D(y) Valsalva were significantly different. Bland and
      Altman analysis showed D(y) Rest, D(y) Kegel, and D(x) and D(y) Valsalva for both
      reliability experiments to have limits of agreement (LOA's) large enough to
      explain >or=50% of the actual value ranges. Template control LOA's explained
      <or=30% of the actual value ranges. CONCLUSIONS: The reliability of this protocol
      varied according to the conditions analyzed; accurate reliability assessment of
      all conditions required Bland and Altman analysis; and the designation of the
      pubic bone central axis remained a source of variance between investigators. Our
      results suggest Bland and Altman analysis be used with each study that quantifies
      perineal ultrasound.

PMID- 16897753
TI  - Leucine stimulates procollagen alpha1(I) translation on hepatic stellate cells
      through ERK and PI3K/Akt/mTOR activation.
AB  - The essential amino acid leucine has been described to specifically activate
      signaling pathways leading to the activation of the translational machinery and
      the increase of total protein synthesis. Regulation of type I collagen production
      by hepatic stellate cells (HSC) is a multistep process involving transcriptional
      and post-transcriptional mechanisms. In the present work we studied the effect of
      leucine on translation regulation of collagen alpha1(I) production in HSC and the
      signaling pathways involved. Treatment of HSC with 5 mM leucine did not alter
      half-life or steady state levels of procollagen alpha1(I) mRNA, but caused an
      increase in procollagen alpha1(I) protein that correlated with changes of
      components involved in translational regulation, like enhanced 4E-BP1, Mnk-1, and
      eIF4E phosphorylation. Leucine also induced mTOR, ERK, and Akt phosphorylation in
      HSC, without affecting p38 and JNK activation. Pre-treatment of HSC with
      PD098059, wortmannin, or rapamycin prevented the profibrogenic action of leucine
      due to the inhibition of different molecular mechanisms. These results suggest
      leucine is a profibrogenic agent for HSC, activating signaling pathways that lead
      to an enhancement of collagen alpha1(I) production through translational
      regulation.

PMID- 16897752
TI  - Myotube depolarization generates reactive oxygen species through NAD(P)H oxidase;
      ROS-elicited Ca2+ stimulates ERK, CREB, early genes.
AB  - Controlled generation of reactive oxygen species (ROS) may contribute to
      physiological intracellular signaling events. We determined ROS generation in
      primary cultures of rat skeletal muscle after field stimulation (400 1-ms pulses
      at a frequency of 45 Hz) or after depolarization with 65 mM K+ for 1 min. Both
      protocols induced a long lasting increase in dichlorofluorescein fluorescence
      used as ROS indicator. Addition of diphenyleneiodonium (DPI), an inhibitor of
      NAD(P)H oxidase, PEG-catalase, a ROS scavenger, or nifedipine, an inhibitor of
      the skeletal muscle voltage sensor, significantly reduced this increase. Myotubes
      contained both the p47phox and gp91phox phagocytic NAD(P)H oxidase subunits, as
      revealed by immunodetection. To study the effects of ROS, myotubes were exposed
      to hydrogen peroxide (H2O2) at concentrations (100-200 microM) that did not alter
      cell viability; H2O2 induced a transient intracellular Ca2+ rise, measured as
      fluo-3 fluorescence. Minutes after Ca2+ signal initiation, an increase in ERK1/2
      and CREB phosphorylation and of mRNA for the early genes c-fos and c-jun was
      detected. Inhibition of ryanodine receptor (RyR) decreased all effects induced by
      H2O2 and NAD(P)H oxidase inhibitors DPI and apocynin decreased ryanodine
      sensitive calcium signals. Activity-dependent ROS generation is likely to be
      involved in regulation of calcium-controlled intracellular signaling pathways in
      muscle cells.

PMID- 16897755
TI  - PAK4 and alphaPIX determine podosome size and number in macrophages through
      localized actin regulation.
AB  - Podosomes are actin-rich adhesion structures typical for monocytic cells and are
      implicated in migration and invasion. Major modes of podosome regulation include
      RhoGTPase signaling and actin regulatory pathways. However, it is not clearly
      understood how these signals induce highly localized changes in podosome
      formation and dynamics. Here, we show that the RhoGTPase effector PAK4, a member
      of the p21 associated kinase family, and its regulator alphaPIX (PAK-interacting
      exchange factor), are central to podosome formation in primary human macrophages.
      Immunofluorescence, biochemical and microarray data indicate that PAK4 acts as
      physiological regulator of podosomes in this system. Accordingly, transfection of
      a specific shRNA, as well as expression of PAK4 truncation mutants, resulted in
      reduced numbers of podosomes per cell. Moreover, expression of kinase active or
      inactive PAK4 mutants enhanced or reduced the size of individual podosomes,
      respectively, indicating a modulatory influence of PAK4 kinase activity on
      podosome size. Similar to the results gained with PAK4, cellular/overexpressed
      PIX was shown to be closely associated with podosomes. Moreover, both
      overexpression of alphaPIX wt and a mutant lacking the SH3 domain led to
      coalescence of podosomes. In sum, we propose that PAK4 and alphaPIX can induce
      highly localized changes in actin dynamics and thereby regulate size and number
      of podosomes in primary human macrophages.

PMID- 16897754
TI  - Subnuclear localization and differentiation-dependent increased expression of DGK
      zeta in C2C12 mouse myoblasts.
AB  - Diacylglycerol kinases (DGKs) catalyze phosphorylation of diacylglycerol (DG) to
      yield phosphatidic acid (PA). Previous evidence has shown that the nucleus
      contains several DGK isoforms. In this study, we have analyzed the expression and
      subnuclear localization of DGK-zeta employing C2C12 mouse myoblasts.
      Immunocytochemistry coupled to confocal laser scanning microscopy showed that
      both endogenous and green fluorescent protein-tagged overexpressed DGK-zeta
      localized mostly to the nucleus. In contrast, overexpressed DGK-alpha, -beta, 
      delta, and -iota did not migrate to the nucleus. DGK-zeta was present in the
      nuclear speckle domains, as also revealed by immuno-electron microscopy analysis.
      Moreover, DGK-zeta co-localized and interacted with phosphoinositide-specific
      phospholipase Cbeta1 (PLCbeta1), that is involved in inositide-dependent
      signaling pathways important for the regulation of cell proliferation and
      differentiation. Furthermore, we report that DGK-zeta associated with nuclear
      matrix, the fundamental organizing principle of the nucleus where many cell
      functions take place, including DNA replication, gene expression, and protein
      phosphorylation. Nuclear DGK-zeta increased during myogenic differentiation of
      C2C12 cells, while DGK-zeta down-regulation by siRNA markedly impaired
      differentiation. Overall, our findings further support the importance of speckles
      and nuclear matrix in lipid-dependent signaling and suggest that nuclear DGK-zeta
      might play some fundamental role during myogenic differentiation of C2C12 cells.

PMID- 16897756
TI  - Regulatory volume increase (RVI) by in situ and isolated bovine articular
      chondrocytes.
AB  - Metabolism of the matrix by chondrocytes is sensitive to alterations in cell
      volume that occur, for example, during static loading and osteoarthritis. The
      ability of chondrocytes to respond to changes in volume could be important, and
      this study was aimed at testing the hypothesis that chondrocytes can regulate
      their volume following cell shrinking by regulatory volume increase (RVI). We
      used single cell fluorescence imaging of in situ bovine articular chondrocytes,
      cells freshly isolated into 280 or 380 mOsm, or 2-D cultured chondrocytes loaded
      with calcein or fura-2, to investigate RVI and changes to [Ca2+]i during
      shrinkage. Following a 42% hyperosmotic challenge, chondrocytes rapidly shrunk,
      however, only approximately 6% of the in situ or freshly isolated chondrocytes
      demonstrated RVI. This contrasted with 2D-cultured chondrocytes where
      approximately 54% of the cells exhibited RVI. The rate of RVI was the same for
      all preparations. During the 'post-RVD/RVI protocol', approximately 60% of the in
      situ and freshly isolated chondrocytes demonstrated RVD, but only approximately
      5% showed RVI. There was no relationship between [Ca2+]i and RVI either during
      hyperosmotic challenge, or during RVD suggesting that changes to [Ca2+]i were not
      required for RVI. Depolymerisation of the actin cytoskeleton by latrunculin,
      increased RVI by freshly isolated chondrocytes, in a bumetanide-sensitive manner.
      The results showed that in situ and freshly isolated articular chondrocytes have
      only limited RVI capacity. However, RVI was stimulated by treating freshly
      isolated chondrocytes with latrunculin B and following 2D culture of
      chondrocytes, suggesting that cytoskeletal integrity plays a role in regulating
      RVI activity which appears to be mediated principally by the Na+ - K+ -2Cl-
      cotransporter.

PMID- 16897758
TI  - P-Akt expression distinguishes two types of malignant rhabdoid tumors.
AB  - Highly aggressive pediatric malignant rhabdoid tumors (MRT) arise in the kidney
      and central nervous system (CNS) with no curative treatment available. Multiple
      studies have shown that inactivation of the SNF5 tumor suppressor gene occurs in
      virtually all MRTs. However, few studies have addressed whether additional
      genetic events may contribute to MRT development. In this report, we demonstrate
      that phosphorylated Akt (P-Akt) is expressed in a subpopulation of cells in at
      least 10% of primary rhabdoid tumors as well as at high levels in three MRT cell
      lines. Similar to other high P-Akt expressing tumor cell lines, MRTs have
      decreased sensitivity to p21 induced growth arrest. Therefore, P-Akt expression
      may distinguish between two types of MRTs. Because drugs directed against the PI3
      K/Akt have shown promise in clinical trials for other tumor types, they may prove
      useful for treatment of patients with P-Akt positive MRTs. P-Akt expression also
      provides a potential mechanistic link between these pediatric tumors and adult
      malignancies.

PMID- 16897757
TI  - Selective amino acid restriction targets mitochondria to induce apoptosis of
      androgen-independent prostate cancer cells.
AB  - Relative specific amino acid dependency is one of the metabolic abnormalities of
      cancer cells, and restriction of specific amino acids induces apoptosis of
      prostate cancer cells. This study shows that restriction of tyrosine and
      phenylalanine (Tyr/Phe), glutamine (Gln), or methionine (Met), modulates Raf and
      Akt survival pathways and affects the function of mitochondria in DU145 and PC3,
      in vitro. These three restrictions inhibit energy production (ATP synthesis) and
      induce generation of reactive oxygen species (ROS). Restriction of Tyr/Phe or Met
      in DU145 and Met in PC3 reduces mitochondrial membrane potential (DeltaPsim) and
      induces caspase-dependent and -independent apoptosis. In DU145, Tyr/Phe or Met
      restriction reduces activity of Akt, mitochondrial distribution of phosphorylated
      Raf and apoptosis inducing factor (AIF), and increases mitochondrial distribution
      of Bak. Mitochondrial Bcl-XL is increased in Tyr/Phe-restricted but decreased in
      Met-restricted cells. Under Tyr/Phe or Met restriction, reduced mitochondrial Raf
      does not inactivate the pro-apoptotic function of Bak. Tyr/Phe restriction also
      inhibits Bcl-2 and Met restriction inhibits Bcl-XL in mitochondria. These
      comprehensive actions damage the integrity of the mitochondria and induce
      apoptosis of DU145. In PC3, apoptosis induced by Met restriction was not
      associated with alterations in intracellular distribution of Raf, Bcl-2 family
      proteins, or AIF. All of the amino acid restrictions inhibited Akt activity in
      this cell line. We conclude that specific amino acid restriction differentially
      interferes with homeostasis/balance between the Raf and Akt survival pathways and
      with the interaction of Raf and Bcl-2 family proteins in mitochondria to induce
      apoptosis of DU145 and PC3 cells.

PMID- 16897761
TI  - Tetrodotoxin for prolonged local anesthesia with minimal myotoxicity.
AB  - Conventional local anesthetics such as bupivacaine cause considerable myotoxicity
      and neurotoxicity, whereas tetrodotoxin (TTX) does not. Tetrodotoxin combined
      with bupivacaine or vasoconstrictors produces long-duration nerve blockade. To
      assess whether these prolonged blocks can be produced without increased
      myotoxicity, Sprague-Dawley rats were injected with bupivacaine, TTX, and both,
      or TTX plus epinephrine. Median durations of thermal nociceptive blockade were,
      respectively, 188, 401, 882, and 972 min. On dissection 4 days later, all tissues
      appeared macroscopically pristine. Muscle injury was at most mild to moderate in
      all animals, and the muscle injury scores for the combination formulations were
      not higher than for bupivacaine alone. Similarly, in differentiated cells from a
      myoblast cell line (C2C12), TTX caused either no or minimal worsening of cell
      viability from bupivacaine at 2 or 7 days. Epinephrine did not worsen TTX's
      relatively minimal cytotoxicity. Tetrodotoxin may thus be useful in producing
      prolonged nerve block with minimal myotoxicity and perhaps neurotoxicity.

PMID- 16897762
TI  - Do carbamates cause polyneuropathy?
AB  - Carbamates are reversible inhibitors of acetylcholinesterase, and some also
      inhibit neuropathy target esterase (NTE), the target in organophosphate-induced
      delayed polyneuropathy. However, based on mechanistic considerations, these
      carbamates were thought to be unable to initiate polyneuropathy. Consequently,
      clinical reports of polyneuropathy associated with carbamate exposures have been
      disregarded. We discuss three cases of polyneuropathy that occurred after severe
      poisoning by methylcarbamates. In addition, high repeated doses of phenyl N
      methyl N-benzylcarbamate caused nearly 100% NTE inhibition and polyneuropathy in
      the hen model. These data suggest the need to reconsider the long-standing tenet
      that carbamates cannot cause polyneuropathy. Alternatively, a preexisting
      subclinical neuropathy in these individuals may have been amplified by
      carbamates, as observed in animal models. We suggest that individuals with
      underlying neuropathy (e.g., diabetics) who are poisoned by carbamates should be
      followed closely. In addition, procedures for the current risk assessment of
      carbamate pesticides may need to be reconsidered.

PMID- 16897763
TI  - Late appearance of dropped head syndrome after radiotherapy for Hodgkin's
      disease.
AB  - We present three cases of dropped head syndrome that occurred as a complication
      of mantle field (i.e., lymph nodes of the neck, axillae, and mediastinum) or
      whole-body radiation therapy for Hodgkin's disease. These cases are characterized
      by a late onset (2-27 years after radiation treatment), fibrosis, and contraction
      of the anterior cervical muscles, and atrophy of the posterior neck and shoulder
      girdle. This report adds to the increasing literature about the late neurological
      complications of radiation therapy and describes a previously unrecognized cause
      of dropped head syndrome.

PMID- 16897764
TI  - Discrimination of normal, benign, and malignant breast tissues by Raman
      spectroscopy.
AB  - Breast cancers are the leading cancers among females. Diagnosis by fine needle
      aspiration cytology (FNAC) is the gold standard. The widely practiced screening
      method, mammography, suffers from high false positive results and repeated
      exposure to harmful ionizing radiation. As with all other cancers survival rates
      are shown to heavily depend on stage of the cancers (Stage 0, 95%; Stage IV,
      75%). Hence development of more reliable screening and diagnosis methodology is
      of considerable interest in breast cancer management. Raman spectra of normal,
      benign, and malignant breast tissue show significant differences. Spectral
      differences between normal and diseased breast tissues are more pronounced than
      between the two pathological conditions, malignant and benign tissues. Based on
      spectral profiles, the presence of lipids (1078, 1267, 1301, 1440, 1654, 1746 cm(
      1)) is indicated in normal tissue and proteins (stronger amide I, red shifted
      DeltaCH2, broad and strong amide III, 1002, 1033, 1530, 1556 cm(-1)) are found in
      benign and malignant tissues. The major differences between benign and malignant
      tissue spectra are malignant tissues seem to have an excess of lipids (1082,
      1301, 1440 cm(-1)) and presence of excess proteins (amide I, amide III, red
      shifted DeltaCH2, 1033, 1002 cm(-1)) is indicated in benign spectra. The
      multivariate statistical tool, principal components analysis (PCA) is employed
      for developing discrimination methods. A score of factor 1 provided a reasonable
      classification of all three tissue types. The analysis is further fine-tuned by
      employing Mahalanobis distance and spectral residuals as discriminating
      parameters. This approach is tested both retrospectively and prospectively. The
      limit test, which provides the most unambiguous discrimination, is also
      considered and this approach clearly discriminated all three tissue types. These
      results further support the efficacy of Raman spectroscopic methods in
      discriminating normal and diseased breast tissues.

PMID- 16897765
TI  - Polarized infrared microspectroscopy of single spruce fibers: hydrogen bonding in
      wood polymers.
AB  - We studied wood polymers in their native composite structure using mechanically
      isolated single spruce (Picea abies [L.] Karst.) fibers. Dichroic infrared
      spectra of fibers placed in a custom-built microfluidic cuvette were acquired in
      air, in liquid (heavy) water, and in liquid dimethylacetamide using a novel
      combination of synchrotron-based Fourier transform infrared microspectroscopy
      with polarization modulation. Differences were observed in the O-H stretching
      frequency region of the spruce spectra upon changing the ambient conditions.
      Analysis of these spectral variations provides information on hydrogen bonding,
      orientation, and accessibility of structural units of the wood polymers in the
      spruce cell walls. Our in situ approach contributes to a further understanding of
      the structural details of wood polymers in their native setting.

PMID- 16897766
TI  - Kinesthesia: the role of muscle receptors.
AB  - The kinesthetic sense, the sense of position and movement of our limbs, has been
      the subject of speculation for more than 400 years. The present-day view is that
      it is signaled principally by muscle spindles, with a subsidiary role played by
      skin and joint receptors. The problem with muscle spindles as position sensors is
      that they are able to generate impulses in response to muscle length changes as
      well as from fusimotor activity. The central nervous system must be able to
      distinguish between activity from the two sources. Recent observations on
      position sense after fatigue and during load-bearing suggest that an additional
      source of kinesthetic information comes from a centrally generated sensation, the
      sense of effort. This has consequences for kinesthesia in the presence of the
      force of gravity. A contribution from central feedback mechanisms to the sense of
      effort is relevant to certain clinical conditions.

PMID- 16897767
TI  - Spatially localized intermolecular zero-quantum coherence spectroscopy for in
      vivo applications.
AB  - Magnetic resonance spectroscopy (MRS) techniques that use the distant dipolar
      field (DDF) to locally refocus inhomogeneous line-broadening promise improved
      spectral resolution in spatially varying fields. We investigated three possible
      implementations of localized DDF spectroscopy. Theoretical analysis and phantom
      experiments at 17.6 T showed that only localization immediately prior to
      acquisition provides sufficient spatial selectivity and sensitivity for in vivo
      applications. Spectra from an (8 mm)(3) voxel of the rat brain were acquired in
      25 min, and three major metabolites were resolved. In a tumor mouse model, DDF
      spectra with well-resolved lines can be obtained from significantly larger voxels
      compared to conventional localized spectroscopy. From an inhomogeneous voxel,
      improved spectral resolution can be obtained with DDF techniques when a
      sufficient number of increments are sampled along the second spectral dimension.
      With fewer increments, measurement time is significantly shortened, and DDF
      techniques can provide higher signal-to-noise ratio (SNR) efficiency.

PMID- 16897768
TI  - In vivo cellular imaging of lymphocyte trafficking by MRI: a tumor model approach
      to cell-based anticancer therapy.
AB  - The aim of this study was to demonstrate the feasibility of in vivo cell tracking
      to monitor anticancer cell therapy by means of a high-resolution noninvasive MRI
      method. Ovalbumin-specific splenocytes (OT-1) labeled with anionic gamma-Fe2O3
      superparamagnetic iron oxide (SPIO) nanoparticles were adoptively transferred
      into C57BL/6 mice with growing ovalbumin-expressing tumors. OT-1 cells were
      tracked in vivo by 7 T MRI 24, 48, and 72 hr after they were injected. The
      results showed significant negative enhancement of the spleen at 24 hr, and of
      the tumor at 48 and 72 hr, after labeled cell injection. This suggests that the
      lymphocytes initially homed toward the spleen and were then recruited by the
      tumor. The presence of labeled cells was confirmed in ex vivo by 9.4 T
      microimaging of tumors and magnetic sorting of spleen cells. These results
      confirm that MR tracking of lymphocytes is feasible in vivo. This high-resolution
      imaging method could be used to improve the monitoring of immune cell therapy.

PMID- 16897769
TI  - Complex relationship between changes in oxygenation status and changes in R*2:
      the case of insulin and NS-398, two inhibitors of oxygen consumption.
AB  - Insulin and NS-398 have been reported to inhibit oxygen consumption in
      experimental tumor models, thereby increasing oxygenation and radiosensitization.
      The aim of this work was to use MRI to study changes in murine FSaII tumor
      hemodynamics after administration of those oxygen consumption inhibitors. A
      multiple-echo gradient-echo (GRE) MRI sequence (4.7 T) was used to map changes in
      three factors: the GRE signal (at TE=20 ms), the parameter S0 (theoretical signal
      at TE=0 ms), and the relaxation rate R*2. Perfusion maps were obtained by dynamic
      contrast-enhanced (DCE) MRI. Insulin caused a significant decrease in the tumor
      blood oxygen level-dependent (BOLD) signal over time. factor This was likely the
      result of decreased blood flow, since both S0 and the percentage of perfused
      tumor decreased as well. Tumor R*2 did not change significantly in response to
      the treatments, which is surprising considering that other non-MRI techniques
      (electron paramagnetic resonance (EPR) oximetry and fiber-optic probes) have
      shown that tumor oxygenation increases after treatment. This suggests that
      metabolic changes associated with vasoactive challenges may have an unpredictable
      influence on blood saturation and R*2. In conclusion, this study further
      emphasizes the fact that changes in BOLD signal and R*2 in tumors do not depend
      uniquely on changes in oxygenation status.

PMID- 16897770
TI  - x-f Choice: reconstruction of undersampled dynamic MRI by data-driven alias
      rejection applied to contrast-enhanced angiography.
AB  - A technique for reconstructing dynamic undersampled MRI data, termed "x-f
      choice," was developed and applied to dynamic contrast-enhanced MR angiography
      (DCE-MRA). Regular undersampling in k-t space (a hybrid of k-space and time)
      creates aliasing in the conjugate x-f space that must be resolved. When regions
      in the object containing fast dynamic change are sparse, as in DCE-MRA, signal
      overlap caused by aliasing is often much less than the undersample factor would
      imply. x-f Choice reconstruction identifies overlapping signals using a model of
      the full non-aliased x-f space that is automatically generated from the
      undersampled data, and applies parallel imaging (PI) to separate them. No extra
      reference scans are required to generate either the model or the coil sensitivity
      maps. At each location in the reconstructed images, g-factor noise amplification
      is compared with predicted reconstruction errors to obtain an optimized solution.
      Acceleration factors greater than the number of receiver coils are possible, but
      are limited by the sparseness of the dynamic content and the signal-to-noise
      ratio (SNR) (in DCE-MRA the latter is dominant). Temporal fidelity was validated
      for up to a factor 10 speed-up using retrospectively undersampled data from a six
      coil array. The method was tested on volunteers using fivefold prospective
      undersampling.

PMID- 16897771
TI  - Crystal structure of GlcAT-S, a human glucuronyltransferase, involved in the
      biosynthesis of the HNK-1 carbohydrate epitope.
AB  - The HNK-1 carbohydrate epitope is found in various neural cell adhesion
      molecules. Two glucuronyltransferases (GlcAT-P and GlcAT-S) are involved in the
      biosynthesis of HNK-1 carbohydrate. Our previous study on the crystal structure
      of GlcAT-P revealed the reaction and substrate recognition mechanisms of this
      enzyme. Comparative analyses of the enzymatic activities of GlcAT-S and GlcAT-P
      showed that there are notable differences in the acceptor substrate specificities
      of these enzymes. To elucidate differences between their specificities, we now
      solved the crystal structure of GlcAT-S. Residues interacting with UDP molecule,
      which is a part of the donor substrate, are highly conserved between GlcAT-P and
      GlcAT-S. On the other hand, there are some differences between these proteins in
      the manner they recognize their respective acceptor substrates. Phe245, one of
      the most important GlcAT-P residues for the recognition of acceptors, is a
      tryptophan in GlcAT-S. In addition, Val320, which is located on the C-terminal
      long loop of the neighboring molecule in the dimer and critical in the
      recognition of the acceptor sugar molecule by the GlcAT-P dimer, is an alanine in
      GlcAT-S. These differences play key roles in establishing the distinct
      specificity for the acceptor substrate by GlcAT-S, which is further supported by
      site-directed mutagenesis of GlcAT-S and a computer-aided model building of GlcAT
      S/substrate complexes.

PMID- 16897772
TI  - Variation in cortical bone histology within the human femur and its impact on
      estimating age at death.
AB  - Histological methods for the estimation of age at death using cortical bone are
      based on the evaluation of microstructural changes over time. Since histological
      analysis is a destructive method, most techniques attempt to limit the amount of
      cortical bone needed for analysis. Sample location, however, can have a
      significant effect on the accuracy of these methods. Furthermore, research
      demonstrates that both intersection and intrasection variation is present at the
      midshaft of the femur, which is the primary location for estimating age at death
      in humans. This research determines the extent of regional variation within the
      adult human femur and its effect on age estimation. Secondary osteon lamellae and
      Haversian canal ratio and cortical thickness were quantified. Thompson's All
      Males Left Femur regression equation was used to estimate age. Results show that
      significant regional variation occurs in the estimated ages derived from the
      posterior aspect of the femoral shaft and significant intrasection variation
      occurs in age estimates from the mid and mid-distal cross-sections. Thus, the
      inter and intrasection variation that occurs in bone remodeling within the
      femoral cortex has the potential to produce significant differences amongst age
      estimates taken from various femoral diaphyseal locations compared to the age
      estimated from the standard location used in Thompson's core method (1978). The
      results indicate that the use of this histological method is dependant on the
      ability to correctly identify the four anatomical locations, but the extracted
      core used for age estimation is not necessarily confined to the anterior
      midshaft.

PMID- 16897773
TI  - Intraskeletal variability in bone mass.
AB  - For methodological or other reasons, a variety of skeletal elements are analyzed
      and subsequently used as a basis for describing general bone loss and mass.
      However, bone loss and mass may not be uniform within and among skeletal elements
      of the same individual because of biomechanical factors. We test the hypothesis
      that a homogeneity in bone mass exists among skeletal elements of the same
      individual. Measures indicative of bone mass were calculated from the midshafts
      of six skeletal elements from the same individuals (N = 41). The extent of
      intraskeletal variability in bone mass (relative cortical area) was then examined
      for the entire sample, according to age, sex, and pathological status. The
      results of the analysis showed that all measures reflect a heterogeneity in bone
      mass (P </= 0.001). Specifically, differences were observed between the bones of
      the upper limb and those of the lower limb. Both sexes showed intraskeletal
      variability in bone mass, but the difference between the sexes is not significant
      (P = 0.509). When the sample is subdivided according to age, all groups show
      intraskeletal variability in bone mass, but the difference did not differ
      significantly among the groups (P = 0.217). However, significant differences in
      intraskeletal variability are observed between individuals below and above the
      age of 50. Pathological individuals show intraskeletal variability in bone mass,
      but the difference between the pathological and non-pathological groups is not
      significant (P = 0.095). These results indicate that the bone mass of any
      particular skeletal element is intricately tethered to its specific mechanical
      loading environment.

PMID- 16897774
TI  - Early childhood stress and adult age mortality--a study of dental enamel
      hypoplasia in the medieval Danish village of Tirup.
AB  - This study explores how linear enamel hypoplasia (LEH) affects mortality in the
      village of Tirup (A.D. 1150-1350), Denmark. Data consist of information on 583
      skeletons aged 1 year or more. Three partly overlapping subsamples were defined.
      (1) 104 skeletons of young children aged 1-6 years and 120 skeletons of adults
      giving information on LEH. (2) 458 skeletons aged 6 years or more. (3) 109 adult
      skeletons (aged 20 years or more) that provided transition analysis age
      estimates, sex assessments, and LEH information. Of the 109 skeletons in
      Subsample 3, 60 had no and 49 had at least one LEH. In Subsample 1, it was found
      that the case fatality rate for episodes potentially leading to LEH dropped from
      over 0.5 in 1-year olds to around 0.1 in 3-5-year olds. Only models with
      heterogeneity of frailty could describe late childhood and adolescent mortality.
      Further, it was shown that only a model with continuously varying frailty
      preserved heterogeneity to adulthood. Among young adult females and males in all
      adult ages, people with LEH experienced a higher mortality than people without
      it. Among males, the mortality rate ratio (MRR) was 2.28. The analyses indicate
      that the MRR gives an unbiased estimate for the extra risk of dying for adult
      males with LEH. The values of the case fatality rates for young children might be
      slightly biased upward because of a higher than average number of older children
      and adolescents dying with LEH.

PMID- 16897776
TI  - Transient expression of endothelins in the amoeboid microglial cells in the
      developing rat brain.
AB  - Amoeboid microglial cells (AMC) which transiently exist in the corpus callosum in
      the postnatal rat brain expressed endothelins (ETs), specifically endothelin-1
      (ET-1) and ET3 as revealed by real time RT-PCR. ET immunoreactive AMC occurred in
      large numbers at birth, but were progressively reduced with age and were
      undetected in 14 days. In rats subjected to hypoxia exposure, ET immunoexpression
      in AMC was reduced but the incidence of apoptotic cells was not increased when
      compared with the control suggesting that this was due to its downregulation that
      may help regulate the constriction of blood vessels bearing ET-A receptor. AMC
      were endowed ET-B receptor indicating that ET released by the cells may also act
      via an autocrine manner. In microglia activated by lipopolysaccharide (LPS), ET-1
      mNA expression coupled with that of monocyte chemoattractant protein (MCP-1) and
      stromal derived factor-1 (SDF-1) was markedly increased; ET-3 mRNA, however,
      remained unaffected. AMC exposed to oxygen glucose deprivation (OGD) in vitro
      resulted in increase in both ET-1 and ET-3 mRNA expression. It is suggested that
      the downregulated ETs expression in vivo of AMC subjected to hypoxia as opposed
      to its upregulated expression in vitro may be due to the complexity of the brain
      tissue. Furthermore, the differential ET-1 and ET-3 mRNA expression in LPS and
      OGD treatments may be due to different signaling pathways independently
      regulating the two isoforms. The present novel finding has added microglia as a
      new cellular source of ET that may take part in multiple functions including
      regulating vascular constriction and chemokines release.

PMID- 16897777
TI  - Microbial induction of CARD15 expression in intestinal epithelial cells via toll
      like receptor 5 triggers an antibacterial response loop.
AB  - With the discovery of CARD15 as susceptibility gene for Crohn's disease (CD) a
      first link to a potential defect in the innate immune system was made. In this
      work we aimed to analyze enterocyte NOD2/CARD15 expression and regulation in
      response to bacterial motifs and the consequences of the most common CD-specific
      CARD15 mutation on antibacterial responses of normal intestinal epithelial cells
      (IEC). Under normal conditions, IEC lines and ileal enterocytes did not express
      NOD2/CARD15 mRNA or protein, contrary to IEC derived from inflammatory CD
      sections. In vitro analyses revealed that the simple contact with non-pathogenic
      commensal E. Coli K12 was sufficient to induced NOD2/CARD15 mRNA and protein in
      human IEC (HIEC). We identified bacterial flagellin interacting with TLR5 as
      major motif in this regulation of NOD2/CARD15. E. Coli mutants not expressing
      flagellin (DeltaFliC) failed to induce CARD15. Similarly, in HIEC transfected
      with a plasmid encoding dominant negative TLR5, no CARD15 induction was observed
      after K12 contact. Isolated TLR2 or TLR4 stimulation had no or only a marginal
      effect on NOD2/CARD15 expression. NOD2/CARD15 negative HIEC were unresponsive to
      muramyl dipeptide (MDP), but once NOD2/CARD15 was induced, HIEC and Caco2 cells
      responded to intra or extracellular MDP presentation with the activation of the
      NFkB pathway. IEC transfected with the Crohn-specific CARD15 mutant (F3020insC,
      FS) failed to activate NFkB after MDP-challenge, in contrast to CARD15WT IEC. In
      response to MDP, IEC induced a massive antibacterial peptide (ABP) response, seen
      in the apical release of CCL20. This was completely abolished in IEC carrying
      CARD15FS. These data suggest a critical role of NOD2/CARD15 in the bacterial
      clearance of the intestinal epithelium while CD-specific mutated NOD2/CARD15
      causes an impaired epithelial barrier.

PMID- 16897778
TI  - Use of Taxus polymer-coated paclitaxel-eluting stents for treatment of in-stent
      restenosis in real world patients: results of clinical and angiographic follow-up
      at six months in a single-center registry.
AB  - OBJECTIVE: To evaluate the safety and efficacy of Taxus paclitaxel-eluting stents
      in a real world group of unselected patients with coronary in-stent restenosis
      (ISR) lesions. METHODS: This is a prospective single-center registry of a
      consecutive series of 94 patients with 104 ISR lesions, without previous
      brachytherapy, over a period of 1 year. Quantitative coronary angiographic
      analyses were performed at baseline and at 6-month angiographic follow-up.
      Clinical follow-up were obtained at 6 months. RESULTS: Pre-intervention mean
      reference vessel diameter was 2.62 +/- 0.50 mm and mean lesion length was 13.95
      +/- 6.78 mm. Baseline ISR patterns were mostly either Type I focal (32.7%) or
      Type II diffuse intrastent (48.1%). At 6-month angiographic follow-up, the in
      stent and in-segment binary restenosis was 3.8% (4/105) and 7.6% (8/105)
      respectively, and the in-stent and in-segment late loss was 0.30 +/- 0.50 mm and
      0.57 +/- 0.54 mm, respectively. Seven of these eight restenosed lesions had a
      diffuse or proliferative ISR pattern prior to intervention. Lesions that
      restenosed had longer mean stent length per lesion (37.3 mm vs. 22.5 mm in
      nonrestenosed group; P = 0.001) and more likely to have had a pattern of total
      occlusion pre-intervention (25.0% vs. 3.1% in nonrestenosed group; P = 0.046). At
      6-month clinical follow-up, the MACE rate was 8.5% and target lesion
      revascularization rate was 7.4%. There was no death but subacute stent thrombosis
      occurred in 1 patient (1.1%) at 3 days after intervention. CONCLUSIONS:
      Paclitaxel-eluting Taxus stent for the treatment of ISR effectively suppresses
      recurrent neointimal proliferation, and was safe and efficacious at 6-month
      follow-up.

PMID- 16897779
TI  - Cardiac computed tomography compared to transthoracic echocardiography in the
      management of congenital heart disease.
AB  - OBJECTIVES: To compare cardiac CT and transthoracic echocardiography (TTE) as
      diagnostic utilities in congenital heart disease (CHD) and to determine their
      advantages and limitations. BACKGROUND: TTE is widely used in the evaluation of
      CHD. Recent reports suggested an increasing role of CT. However, there are few
      quantitative data on its diagnostic accuracy. METHODS: We investigated a total of
      162 patients (51.24% male; mean age: 16.06 +/-+/- 17.92) with congenital heart
      defects, who underwent electron beam CT (EBCT) and TTE between March 2002 and
      June 2005. We retrospectively analyzed a total of 667 findings, stratified for
      age and anatomic categories. RESULTS: EBCT and TTE findings are concordant in
      patients below 1 year of age (85.43% agreement). EBCT had poor sensitivity and
      specificity in detecting anomalies of cardiac chambers (0.68, 0.58), but was
      useful for great arteries (0.91, 0.85). Furthermore, sensitivity and specificity
      were remarkably different in systemic venous return (0.93, 0.3) and coronary
      vessels (0.8, 0.33) because of "false positive" findings, which were later found
      to be most likely real findings not detectable by reference standard. The
      opposite was true for cardiac valves (0.66, 0.89) and septa (0.76, 0.91).
      CONCLUSIONS: EBCT delineates findings related to systemic venous return and
      coronary vessels well due to simultaneous visualization of complex anatomy. This
      advantage does not seem to apply in patients below 1 year of age with better
      acoustic windows. TTE was found more suitable for cardiac valves and septal
      defects because of the availability of flow imaging.

PMID- 16897780
TI  - Structure determination of symmetric homo-oligomers by a complete search of
      symmetry configuration space, using NMR restraints and van der Waals packing.
AB  - Structural studies of symmetric homo-oligomers provide mechanistic insights into
      their roles in essential biological processes, including cell signaling and
      cellular regulation. This paper presents a novel algorithm for homo-oligomeric
      structure determination, given the subunit structure, that is both complete, in
      that it evaluates all possible conformations, and data-driven, in that it
      evaluates conformations separately for consistency with experimental data and for
      quality of packing. Completeness ensures that the algorithm does not miss the
      native conformation, and being data-driven enables it to assess the structural
      precision possible from data alone. Our algorithm performs a branch-and-bound
      search in the symmetry configuration space, the space of symmetry axis parameters
      (positions and orientations) defining all possible C(n) homo-oligomeric complexes
      for a given subunit structure. It eliminates those symmetry axes inconsistent
      with intersubunit nuclear Overhauser effect (NOE) distance restraints and then
      identifies conformations representing any consistent, well-packed structure to
      within a user-defined similarity level. For the human phospholamban pentamer in
      dodecylphosphocholine micelles, using the structure of one subunit determined
      from a subset of the experimental NMR data, our algorithm identifies a diverse
      set of complex structures consistent with the nine intersubunit NOE restraints.
      The distribution of determined structures provides an objective characterization
      of structural uncertainty: backbone RMSD to the previously determined structure
      ranges from 1.07 to 8.85 A, and variance in backbone atomic coordinates is an
      average of 12.32 A(2). Incorporating vdW packing reduces structural diversity to
      a maximum backbone RMSD of 6.24 A and an average backbone variance of 6.80 A(2).
      By comparing data consistency and packing quality under different assumptions of
      oligomeric number, our algorithm identifies the pentamer as the most likely
      oligomeric state of phospholamban, demonstrating that it is possible to determine
      the oligomeric number directly from NMR data. Additional tests on a number of
      homo-oligomers, from dimer to heptamer, similarly demonstrate the power of our
      method to provide unbiased determination and evaluation of homo-oligomeric
      complex structures.

PMID- 16897781
TI  - Bladder volume sensitivity of isovolumetric intravesical pressure.
AB  - AIMS: Recently, methods have been introduced for non-invasively measuring the
      isovolumetric bladder pressure. This pressure can also be measured invasively
      using a stop test. In itself, the isovolumetric pressure is a measure of urinary
      bladder contractility, by combining it with maximum urinary flow rate it can be
      used to diagnose infravesical obstruction. We have studied the (possible) volume
      dependence of this pressure in order to enhance the accuracy of this type of
      measurements and to explore its physiological background and possible diagnostic
      relevance. MATERIALS AND METHODS: In 1,020 healthy subjects, recruited for an
      ongoing longitudinal study of changes in bladder contractility secondary to
      prostatic enlargement, we measured the isovolumetric bladder pressure using the
      condom catheter method. In each subject, voiding was repeatedly interrupted. The
      resulting pressure-volume relations were normalized and averaged. RESULTS AND
      CONCLUSIONS: There is an optimum bladder volume for isovolumetric pressure
      measurements, averaging 264 +/- 122 ml (mean +/- SD). Measurements should be
      taken at or above the optimum volume. At volumes below the optimum volume, the
      pressure decreases by approximately 5% for each 10% of volume decrease. At
      bladder volumes smaller than 247 ml pressure readings in 50% of subjects are
      suboptimal. The optimum volume for isovolumetric pressure generation is only
      marginally related to voiding diary parameters. Probably it represents mechanical
      properties of the bladder, whereas voiding diary parameters more likely represent
      neurophysiological properties. However, the optimum volume does not reflect the
      optimum (smooth) muscle length for force generation of the bladder wall: during
      normal voiding bladder smooth muscle always operates at a suboptimal length for
      force generation.

PMID- 16897782
TI  - Assembly of multimeric phage nanostructures through leucine zipper interactions.
AB  - One barrier to the construction of nanoscale devices is the ability to place
      materials into 2D- and 3D-ordered arrays by controlling the assembly and ordering
      of connections between nanomaterials. Ordered assembly of nanoscale materials may
      potentially be achieved using biological tools that direct specific connections
      between individual components. Recently, viruses were successfully employed as
      scaffolds for the nucleation of nanoparticles and nanowires (Mao et al., 2004);
      however, there is a paucity of methods for the higher order assembly of phage
      templated materials. Here we describe a general strategy for the assembly of
      filamentous bacteriophages into long, wire-like or into tripod-like structures.
      To prepare the linear phage assemblies, dimeric leucine zipper protein domains,
      fused to the p3 and p9 proteins of M13 bacteriophage, were employed to direct the
      specific end-to-end self-association of the bacteriophage particles. Electron
      microscopy revealed that up to 90% of the phage displaying complementary leucine
      zipper domains formed linear multi-phage assemblies, composed of up to 30 phage
      in length. To prepare tripod-like assemblies, phage were engineered to express
      trimeric leucine zippers as p3 fusion proteins. This resulted in 3D assembly with
      three individual phages attached at a single point. These ordered phage
      structures should provide a foundation for self-assembly of virally templated
      nanomaterials into useful devices.

PMID- 16897783
TI  - Co-immobilization of different enzyme activities to non-woven polyester surfaces.
AB  - Co-immobilization was applied to combine complementary enzyme reactions.
      Therefore, trypsin was co-immobilized together with both, lipase and alpha
      amylase, onto the surface of non-woven polyester material. The progress of the
      immobilization reaction was directly monitored by investigating covalent fixation
      of the enzymes to the polyester flees using (1)H-MAS-NMR. Co-immobilization of
      the different types of enzymes to the polyester support showed retained enzymatic
      activity. However, a competition of binding to the support was observed.
      Increasing amounts of one type of enzyme reduced the degree of immobilization for
      the other type. In order to investigate the distribution of trypsin and alpha
      amylase on the polyester support, the flees was treated with a mixture of
      rhodamine isothiocyanate labeled with anti-trypsin antibodies and fluorescein
      isothiocyanate labeled with anti-alpha-amylase antibodies. Using fluorescence
      microscopy, the co-immobilization was analyzed by selective excitation of both
      chromophores at 480 and 530 nm, respectively. In addition, fluorescence
      spectroscopy was applied by direct labeling of trypsin and lipase prior to co
      immobilization to the polyester support. A special prism of plexiglass was
      constructed, which fit into a 10 x 10 mm fluorescence cuvette in that way that a
      diagonal plane was formed within the cuvette. The non-woven support was fixed in
      the cuvette and fluorescence spectra were obtained to characterize the amount of
      different enzymes linked to the support. Using FRET it was demonstrated that a
      uniform distribution of the various enzyme species was achieved, where the
      different enzyme activities are bound on the support in close neighborhood to one
      another.

PMID- 16897784
TI  - A theoretical study of oxygen transfer including cell necrosis for the design of
      a bioartificial pancreas.
AB  - In an extravascular bioartificial pancreas (BAP), islet functions are probably
      limited by diffusive mass transfer and local consumption, leading to low
      oxygenation. A mathematical model based on finite elements and focusing on local
      oxygen transport in both the alginate core and the islets of Langerhans has been
      proposed to help design an efficient pancreas supply. It was possible to randomly
      localize islets in a hollow fiber at different densities, and the effects of
      hypoxia and necrosis were included in the mass transfer simulations. Thorough
      study of the numerical results first led to the analysis of several relevant
      parameters, such as necrosis factor and efficacy in terms of insulin secretion,
      as a way to optimize fiber geometry. The approach was then to calculate the
      number of islets that needed to be implanted in order to obtain a correct
      response in terms of insulin secretion. In most configurations, it was found to
      be much higher than that of ultimately functional islets, because of hypoxia and
      necrosis. Fiber length should thus be adjusted accordingly. Finally, we
      demonstrated that the compromise to be found between the reduction of the number
      of implanted islets and fiber length and diameter did not correspond to realistic
      hollow fiber systems. The alternative of using flat geometry was also envisaged
      with more optimistic feasibility assessments.

PMID- 16897786
TI  - Transient intermediates of the Tebbe reagent intercepted and characterized by
      atmospheric pressure chemical ionization mass spectrometry.

PMID- 16897785
TI  - Electron ionization tandem mass spectra of some 3-cyano-4-substituted phenyl-6
      phenyl-2(1H)-pyridones.

PMID- 16897787
TI  - Isotope abundance analysis methods and software for improved sample
      identification with supersonic gas chromatography/mass spectrometry.
AB  - We present newly developed isotope abundance analysis (IAA) methods and software
      which are used to derive elemental formula information from experimental mass
      spectral data of molecular ion isotopomeric abundances. The software, using a
      novel method, can also be used to automatically confirm or reject NIST library
      search results, thereby significantly improving the confidence level in sample
      identifications. In the case of IAA confirmation of the NIST library results,
      sample identification is unambiguous, since the confirmation is achieved by two
      independent sets of data and analytical methods. In the case of a rejection, such
      as when the molecule is not included in the library's databases, the IAA software
      independently provides a list of elemental formulae with declining order of
      matching to the isotopomeric experimental data, in a similar way to accurate mass
      measurements with costly instruments. IAA is ideally applicable to gas
      chromatography/mass spectrometry (GC/MS) (and liquid chromatography/electron
      ionization mass spectrometry (LC/EI-MS)) with a supersonic molecular beam (SMB)
      since it requires a trustworthy and highly abundant true molecular ion that is
      unique to the SMB-MS systems, plus the absence of self chemical ionization and
      vacuum background noise, again unique features of GC/SMB-MS. The various features
      of the IAA methods and software are described, their performance is demonstrated
      with the analysis of experimental GC-SMB-MS data and the IAA concept is compared
      with accurate mass alternatives. The combination of IAA and GC/SMB-MS is believed
      to be superior to accurate mass GC/MS in view of the general availability of
      trustworthy molecular ions for an extended range of compounds.

PMID- 16897788
TI  - 'Information-Based-Acquisition' (IBA) technique with an ion-trap/time-of-flight
      mass spectrometer for high-throughput and reliable protein profiling.
AB  - Highly complex protein mixtures can be analyzed after proteolysis using liquid
      chromatography/mass spectrometry (LC/MS). In an LC/MS run, intense peptide ions
      originating from high-abundance proteins are preferentially analyzed using tandem
      mass spectrometry (MS(2)), so obtaining the MS(2) spectra of peptide ions from
      low-abundance proteins is difficult even if such ions are detected. Furthermore,
      the MS(2) spectra may produce insufficient information to identify the peptides
      or proteins. To solve these problems, we have developed a real-time optimization
      technique for MS(2), called the Information-Based-Acquisition (IBA) system. In a
      preliminary LC/MS run, a few of the most intense ions detected in every MS
      spectrum are selected as precursors for MS(2) and their masses, charge states and
      retention times are automatically registered in an internal database. In the next
      run, a sample similar to that used in the first run is analyzed using database
      searching. Then, the ions registered in the database are excluded from the
      precursor ion selection to avoid duplicate MS(2) analyses. Furthermore, real-time
      de novo sequencing is performed just after obtaining the MS(2) spectrum, and an
      MS(3) spectrum is obtained for accurate peptide identification when the number of
      interpreted amino acids in the MS(2) spectrum is less than five. We applied the
      IBA system to a yeast cell lysate which is a typical crude sample, using a
      nanoLC/ion-trap time-of flight (IT/TOF) mass spectrometer, repeating the same
      LC/MS run five times. The obtained MS(2) and MS(3) spectra were analyzed by
      applying the Mascot (Matrix Science, Boston, MA, USA) search engine to identify
      proteins from the sequence database. The total number of identified proteins in
      five LC/MS runs was three times higher than that in the first run and the ion
      scores for peptide identification also significantly increased, by about 70%,
      when the MS(3) spectra were used, combined with the MS(2) spectra, before being
      subjected to Mascot analysis.

PMID- 16897789
TI  - Determination of dichloroanilines in human urine by gas chromatography/mass
      spectrometry: validation protocol and establishment of Reference Values in a
      population group living in central Italy.
AB  - 3,4- and 3,5-Dichloroanilines (DCAs) are common markers of some non-persistent
      pesticides, e.g. linuron, diuron, vinclozolin, and iprodione. The general
      population may be exposed to these DCAs and/or their precursors mainly through
      diet. Since adverse effects on human health, such as endocrine disruption, have
      been reported, biological monitoring is essential for exposure assessment both of
      occupationally exposed subjects and of the general population. A highly sensitive
      and selective gas chromatography/mass spectrometry (GC/MS) method has been
      developed for the determination of 3,4- and 3,5-DCAs in urine using 4-chloro-2
      methylaniline as an internal standard. The selected ion monitoring (SIM) mode was
      employed for quantitation of the analytes. The sample treatment procedure is
      simple and fast and no derivatization is required. The overall method was
      validated including uncertainty measurement. The limit of detection (LOD) and the
      lower limit of quantitation (LLOQ) were determined to be 0.005 and 0.010 microg/L
      for both analytes. The method was then applied to the establishment of reference
      values for a population group living in a rural area of central Italy
      (Novafeltria, Marche). A total of 151 out of 153 samples were found to be
      positive for 3,5-DCA, and 81.7% were positive for 3,4-DCA. For this group, 3,4
      DCA levels ranged from 0.01 to 6.19 microg/L, while 3,5-DCA urinary
      concentrations were between 0.02 and 6.71 microg/L.

PMID- 16897790
TI  - Analysis of immunoglobulin heavy and light chain variable genes in post
      transplant lymphoproliferative disorders.
AB  - Post-transplant lymphoproliferative disorders (PTLD) derive from antigen
      experienced B-cells and represent a major complication of solid organ
      transplantation. We characterized usage, mutation frequency and mutation pattern
      of immunoglobulin variable (IGV) gene rearrangements in 50 PTLD (polymorphic
      PTLD, n=10; diffuse large B-cell lymphoma, n=35; and Burkitt/Burkitt-like
      lymphoma, n=5). Among PTLD yielding clonal IGV amplimers, a functional IGV heavy
      chain (IGHV) rearrangement was found in 40/50 (80.0%) cases, whereas a
      potentially functional IGV light chain rearrangement was identified in 36/46
      (78.3%) PTLD. By combining IGHV and IGV light chain rearrangements, 10/50 (20.0%)
      PTLD carried crippling mutations, precluding expression of a functional B-cell
      receptor (BCR). Immunohistochemistry showed detectable expression of IG light
      chains in only 18/43 (41.9%) PTLD. Failure to detect a functional IGV
      rearrangement associated with lack of IGV expression. Our data suggest that a
      large fraction of PTLD arise from germinal centre (GC)-experienced B-cells that
      display impaired BCR. Since a functional BCR is required for normal B-cell
      survival during GC transit, PTLD development may implicate rescue from apoptosis
      and expansion of B-cells that have failed the GC reaction. The high frequency of
      IGV loci inactivation appears to be a peculiar feature of PTLD among
      immunodeficiency-associated lymphoproliferations.

PMID- 16897791
TI  - The new Swedish Prescribed Drug Register--opportunities for
      pharmacoepidemiological research and experience from the first six months.
AB  - PURPOSE: To describe the content and potentials of the new Swedish national
      register on prescribed and dispensed medicines. METHODS: The Swedish Prescribed
      Drug Register contains information about age, sex and unique identifier of the
      patient as well as the prescriber's profession and practice. Information
      regarding drug utilization and expenditures for prescribed drugs in the entire
      Swedish population was extracted from the first six months July-December 2005 and
      compared with total drug sales in the country including OTC and hospital use.
      RESULTS: The total quantity of drugs sold in Sweden was 2666 million DDDs,
      corresponding to 1608 DDD/1000 inhabitants daily. The total expenditures were 1.6
      billion Euro. The prescribed drugs, included in the register, accounted for 84%
      of the total utilization and 77% of the total expenditures. About half of all men
      and two-thirds of all women in the country purchased drugs. The proportion
      increased by age. The most common drugs for chronic treatment were diuretics
      among women (8.8% of the population) and antithrombotic agents among men (7.6%).
      Psychotropic drugs, corticosteroids and analgesics were more common among women,
      while men used antithrombotic agents, antidiabetic drugs, lipid lowering agents
      and ACE inhibitors to a greater extent. CONCLUSIONS: The new register provides
      valuable data on exposure to drugs and is useful to study patterns of drug
      utilization. The possibilities for record linkage to other health registers gives
      from an international perspective good opportunities to explore drug and disease
      associations and the risks, benefits, effectiveness and health economical effects
      of drug use.

PMID- 16897792
TI  - Diameter-tunable CdTe nanotubes templated by 1D nanowires of cadmium thiolate
      polymer.

PMID- 16897794
TI  - Synthesis and structure of the "dialuminyne" Na(2)[Ar'AlAlAr'] and
      Na(2)[(Ar''Al)3]: Al--Al bonding in Al2Na2 and Al3Na2 clusters.

PMID- 16897793
TI  - Metal-organic frameworks as efficient materials for drug delivery.

PMID- 16897795
TI  - Li26 clusters in the compound Li13Na29Ba19.

PMID- 16897796
TI  - Direct monitoring of the asymmetric induction of solid-phase catalysis using
      circular dichroism: diamine-Cu(I)-catalyzed asymmetric Henry reaction.

PMID- 16897797
TI  - Regioselective iron-catalyzed allylic amination.

PMID- 16897799
TI  - Reactivity of intein thioesters: appending a functional group to a protein.
AB  - The success of genome sequencing has heightened the demand for new means to
      manipulate proteins. An especially desirable goal is the ability to modify a
      target protein at a specific site with a functional group of orthogonal
      reactivity. Here, we achieve that goal by exploiting the intrinsic
      electrophilicity of the thioester intermediate formed during intein-mediated
      protein splicing. Detailed kinetic analyses of the reaction of nitrogen
      nucleophiles with a chromogenic small-molecule thioester revealed that the alpha
      hydrazino acetyl group was the optimal nucleophile for attacking a thioester at
      neutral pH to form a stable linkage. A bifunctional reagent bearing an alpha
      hydrazino acetamido and azido group was synthesized in high overall yield. This
      reagent was used to attack the thioester linkage between a target protein and
      intein, and thereby append an azido group to the target protein in a single step.
      The azido protein retained full biological activity. Furthermore, its azido group
      was available for chemical modification by Huisgen 1,3-dipolar azide-alkyne
      cycloaddition. Thus, the mechanism of intein-mediated protein splicing provides
      the means to install a useful functional group at a specific site-the C terminus
      of virtually any protein.

PMID- 16897800
TI  - Pd(OAc)2-catalyzed coupling/cyclization of 2,3-allenoic acids and methyl
      propiolate: observation of double 1,7-hydrogen shifts.

PMID- 16897798
TI  - Evidence that a novel thioesterase is responsible for polyketide chain release
      during biosynthesis of the polyether ionophore monensin.
AB  - Polyether ionophores, such as monensin A, are known to be biosynthesised, like
      many other antibiotic polyketides, on giant modular polyketide synthases (PKSs),
      but the intermediates and enzymes involved in the subsequent steps of oxidative
      cyclisation remain undefined. In particular there has been no agreement on the
      mechanism and timing of the final polyketide chain release. We now report
      evidence that MonCII from the monensin biosynthetic gene cluster in Streptomyces
      cinnamonensis, which was previously thought to be an epoxide hydrolase, is a
      novel thioesterase that belongs to the alpha/beta-hydrolase structural family and
      might catalyse this step. Purified recombinant MonCII was found to hydrolyse
      several thioester substrates, including an N-acetylcysteamine thioester
      derivative of monensin A. Further, incubation with a hallmark inhibitor of such
      enzymes, phenylmethanesulfonyl fluoride, led to inhibition of the thioesterase
      activity and to the accumulation of an acylated form of MonCII. These findings
      require a reassessment of the role of other enzymes implicated in the late stages
      of polyether ionophore biosynthesis.

PMID- 16897801
TI  - Kinetic model for reactivity in quaternary water-in-oil microemulsions.
AB  - A study was carried out on the nitrosation of piperazine (PIP) and N
      methylbenzylamine (MeBzAm) by N-methyl-N-nitroso-p-toluenesulfonamide (MNTS) in
      quaternary microemulsions of tetradecyltrimethylammonium bromide
      (TTABr)/isooctane/alcohol/water, varying the nature and the concentration of the
      following alcohols: 1-pentanol, 1-hexanol, 1-heptanol, 1-octanol and 1-decanol
      keeping the [1-alcohol]/[TTABr] = 4 relationship constant. In addition a study
      was carried out on the influence of the alcohol concentration, working with molar
      relationships [1-hexanol]/[TTABr]=3, 4 and 5. On the basis of the molar volumes
      of the alcohol and surfactant and the concentration of alcohol at the interface
      it was possible to calculate the change in its volume with as varying
      compositions of the microemulsion. In order to interpret the experimental results
      a kinetic model was devised which takes into account the distribution of the
      reactants between the different pseudophases and the change in the volume of the
      interface. The rate constants at the interface of the microemulsion are lower
      than in pure water and are independent of the nature of the alcohol used as a
      cosurfactant and the molar relationship [alcohol]/[TTABr]. This independence
      indicates that the main role of the cosurfactant is to increase the volume of the
      interface with the consequent dilution of the reactants.

PMID- 16897802
TI  - Environmentally friendly one-pot synthesis of alpha-alkylated nitriles using
      hydrotalcite-supported metal species as multifunctional solid catalysts.
AB  - A ruthenium-grafted hydrotalcite (Ru/HT) and hydrotalcite-supported palladium
      nanoparticles (Pd(nano)/HT) are easily prepared by treating basic layered double
      hydroxide, hydrotalcite (HT, Mg(6)Al(2)(OH)(16)CO(3)) with aqueous RuCl(3)n H(2)O
      and K(2)[PdCl(4)] solutions, respectively, using surface impregnation methods.
      Analysis by means of X-ray diffraction, and energy-dispersive X-ray, electron
      paramagnetic resonance, and X-ray absorption fine structure spectroscopies proves
      that a monomeric Ru(IV) species is grafted onto the surface of the HT. Meanwhile,
      after reduction of a surface-isolated Pd(II) species, highly dispersed Pd
      nanoclusters with a mean diameter of about 70 A is observed on the Pd(nano)/HT
      surface by transmission electron microscopy analysis. These hydrotalcite
      supported metal catalysts can effectively promote alpha-alkylation reactions of
      various nitriles with primary alcohols or carbonyl compounds through tandem
      reactions consisting of metal-catalyzed oxidation and reduction, and an aldol
      reaction promoted by the base sites of the HT. In these catalytic alpha
      alkylations, homogeneous bases are unnecessary and the only by-product is water.
      Additionally, these catalyst systems are applicable to one-pot syntheses of
      glutaronitrile derivatives.

PMID- 16897803
TI  - Unexpected reaction of the unsaturated cluster host and catalyst [Pd3(mu3
      CO)(dppm)3]2+ with the hydroxide ion: spectroscopic and kinetic evidence of an
      inner-sphere mechanism.
AB  - The title cluster, [Pd(3)(mu(3)-CO)(dppm)(3)](2+)
      (dppm=bis(diphenylphosphino)methane), reacts with one equivalent of hydroxide
      anions (OH(-)), from tetrabutylammonium hydroxide (Bu(4)NOH), to give the
      paramagnetic [Pd(3)(mu(3)-CO)(dppm)(3)](+) species. Reaction with another
      equivalent of OH(-) leads to the zero-valent compound [Pd(3)(mu(3)
      CO)(dppm)(3)](0). From electron paramagnetic resonance analysis of the reaction
      medium using the spin-trap agent 5,5-dimethyl-1-pyrroline-N-oxide (DMPO), the 2
      tetrahydrofuryl or methyl radicals, deriving from the tetrahydrofuran (THF) or
      dimethyl sulfoxide (DMSO) solvent, respectively, were detected. For both
      [Pd(3)(mu(3)-CO)(dppm)(3)](2+) and [Pd(3)(mu(3)-CO)(dppm)(3)](+), the mechanism
      involves, in a first equilibrated step, the formation of a hydroxide adduct,
      [Pd(3)(mu(3)-CO)(dppm)(3)(OH)]((n-1)+) (n=1, 2), which reacts irreversibly with
      the solvent. The kinetics were resolved by means of stopped-flow experiments and
      are consistent with the proposed mechanism. In the presence of an excess of
      Bu(4)NOH, an electrocatalytic process was observed with modest turnover numbers
      (7-8). The hydroxide adducts [Pd(3)(mu(3)-CO)(dppm)(3)(OH)]((n-1)+) (n=1, 2),
      which bear important similarities to the well-known corresponding halide adducts
      [Pd(3)(mu(3)-CO)(dppm)(3)(mu(3)-X)](n) (X=Cl, Br, I), have been studied by using
      density functional theory (DFT). Although the optimised geometry for the cluster
      in its +2 and 0 oxidation states (i.e., cation and anion clusters, respectively)
      is the anticipated mu(3)-OH form, the paramagnetic species, [Pd(3)(mu(3)
      CO)(dppm)(3)(OH)](0), shows a mu(2)-OH form; this suggests an important
      difference in electronic structure between these three species.

PMID- 16897804
TI  - Synthesis, characterization, and self-assembly of nitrogen-containing
      heterocoronenetetracarboxylic acid diimide analogues: photocyclization of N
      heterocycle-substituted perylene bisimides.
AB  - Novel dibenzocoronenetetracarboxylic acid diimide analogues and
      naphthoperylenetetracarboxylic acid diimide analogues containing imidazole, 1,2,4
      triazole, and pyrazole rings embedded as functional constituents within the
      parent hydrocarbon backbone have been synthesized. The pi-rich and pi-poor
      heterocycles have different influences on the physical properties of the parent
      benzocoronenetetracarboxylic acid diimide and naphthoperylenetetracarboxylic acid
      diimide systems. The pi-rich 3 was able to self-assemble into one-dimensional
      nanostructures through strong pi-pi stacking, whereas the pi-poor 8 lacked the
      one-dimensional self-assembly capability, thus offering the potential to control
      the self-assembly capability of the pi-conjugated perylene core by decoration
      with N-heterocycles.

PMID- 16897805
TI  - Property-oriented rational design of single-molecule magnets: a C3-symmetric
      Mn6Cr complex based on three molecular building blocks with a spin ground state
      of St=21/2.

PMID- 16897806
TI  - Solid-state phase transition of an inclusion complex of 5-methyl-2-pyridone with
      1,3,5-benzenetricarboxylic acid.

PMID- 16897808
TI  - Mechanistic studies of catalytic polyethylene chain growth in the presence of
      water.

PMID- 16897807
TI  - Anomeric acetates of N-acetylneuraminic acid are useful C-sialyl donors in
      samarium-mediated reformatsky coupling reactions.

PMID- 16897809
TI  - Metal-compound-induced vesicles as efficient directors for rapid synthesis of
      hollow alloy spheres.

PMID- 16897810
TI  - Halogenated veneers: protein cross-linking and halogenation in the jaws of
      nereis, a marine polychaete worm.
AB  - Mineralized tissues are produced by most living organisms for load and impact
      functions. In contrast, the jaws of the clam worm, Nereis, are hard without
      mineralization. However, they are peculiarly rich in halogens, which are
      associated with a variety of post-translationally modified amino acids, many of
      which are multiply halogenated by chlorine, bromine, and/or iodine. Several of
      these modified amino acids, namely dibromohistidine, bromoiodohistidine,
      chloroiodotyrosine, bromoiodotyrosine, chlorodityrosine, chlorotrityrosine,
      chlorobromotrityrosine, and bromoiodotrityrosine, have not been previously
      reported. We have found that the distributions of Cl, Br, and I differ: Cl is
      widespread whereas Br and I, although not colocalized, are concentrated in
      proximity to the external jaw surfaces. By using nanoindentation, we show that Br
      and I are unlikely to play a purely mechanical role, but that the local Zn and Cl
      concentrations and jaw microstructure are the prime determinants of local jaw
      hardness. Several of the post-translationally modified amino acids are akin to
      those found in various sclerotized structures of invertebrates, and we propose
      that they are part of a cross-linked protein casing.

PMID- 16897811
TI  - Bupropion in pregnancy and the prevalence of congenital malformations.
AB  - PURPOSE: Reports from the GlaxoSmithKline Bupropion Pregnancy Registry suggested
      an increase in cardiovascular defects following exposure to bupropion during
      pregnancy. We conducted a study of congenital malformations among infants born to
      women exposed to bupropion during their first trimester. METHODS: The study used
      data from UnitedHealthcare between January 1995 and September 2004. We calculated
      the prevalence of all congenital malformations and cardiovascular malformations
      associated with bupropion exposure in the estimated first trimester (1213
      infants), compared with (1) other antidepressant exposure in the first trimester
      (4743 infants) and (2) bupropion exposure outside the first trimester (1049
      infants). Malformation cases were confirmed through medical record abstraction.
      We calculated adjusted odds ratios (AORs) using the GEE form of logistic
      regression. RESULTS: For all congenital malformations, the prevalence associated
      with bupropion first trimester was 23.1 per 1000 infants. The AORs were 0.95
      (95%CI 0.62-1.45) and 1.00 (95%CI 0.57-1.73) in comparison to other
      antidepressants (prevalence 23.2 per 1000) and bupropion outside the first
      trimester (prevalence 21.9 per 1000), respectively. For cardiovascular
      malformations, the prevalence associated with bupropion first trimester was 10.7
      per 1000 infants. The AORs were 0.97 (95%CI 0.52-1.80) and 1.07 (95%CI 0.48-2.40)
      in comparison to other antidepressants (prevalence 10.8 per 1000) and bupropion
      outside the first trimester (prevalence 9.5 per 1000), respectively. CONCLUSIONS:
      Results do not support a hypothesis of a teratogenic effect of first trimester
      bupropion exposure. The prevalence of malformations associated with bupropion
      exposure in the first trimester was not increased relative to the comparison
      groups.

PMID- 16897812
TI  - Interpretation of the temperature dependence of equilibrium and rate constants.
AB  - The objective of this review is to draw attention to potential pitfalls in
      attempts to glean mechanistic information from the magnitudes of standard
      enthalpies and entropies derived from the temperature dependence of equilibrium
      and rate constants for protein interactions. Problems arise because the
      minimalist model that suffices to describe the energy differences between initial
      and final states usually comprises a set of linked equilibria, each of which is
      characterized by its own energetics. For example, because the overall standard
      enthalpy is a composite of those individual values, a positive magnitude for
      DeltaH(o) can still arise despite all reactions within the subset being
      characterized by negative enthalpy changes: designation of the reaction as being
      entropy driven is thus equivocal. An experimenter must always bear in mind the
      fact that any mechanistic interpretation of the magnitudes of thermodynamic
      parameters refers to the reaction model rather than the experimental system. For
      the same reason there is little point in subjecting the temperature dependence of
      rate constants for protein interactions to transition-state analysis. If
      comparisons with reported values of standard enthalpy and entropy of activation
      are needed, they are readily calculated from the empirical Arrhenius parameters.

PMID- 16897813
TI  - Impaired regulatory T cell function in germ-free mice.
AB  - Regulatory T cells (Treg) are crucial for the maintenance of tolerance to auto
      antigens and harmless exogenous antigens. Here, we studied the role of the
      commensal microbiota for the development and function of Treg. CD4+CD25+ T cells
      were obtained from peripheral lymph nodes (PLN) and mesenteric lymph nodes (MLN)
      of germ-free (GF) and conventional (conv) NMRI mice and tested for phenotype and
      functional suppressive capacity. CD4+CD25+ T cells from GF mice showed a lower
      relative gene expression of fork head box p3 gene (Foxp3) and were not as potent
      suppressors in vitro as CD4+CD25+ T cells from conv animals. Intracellular
      staining for Foxp3 and CTLA-4 revealed proportional and regional differences in
      putative Treg subsets between conv and GF mice. Fewer of the CD4+CD25+ T cells in
      GF MLN expressed Foxp3 and CTLA-4, while the expression of these markers was
      similar amongst the CD4+CD25+ T cells in PLN of conv and GF mice. The largest
      difference between conv and GF Treg was observed in the liver draining celiac
      lymph node, where GF mice had fewer putative Treg as compared to conv mice. We
      propose that the presence of a microbial flora favors the development of a fully
      functional Treg population.

PMID- 16897814
TI  - Rapid CD40-mediated rescue from CD95-induced apoptosis requires TNFR-associated
      factor-6 and PI3K.
AB  - The activation molecule CD40 and the death receptor CD95/Fas play important roles
      in regulating B cells so that effective antimicrobial immunity occurs without
      autoimmunity. CD40 signaling increases CD95 expression, sensitizing cells to
      apoptosis, but sustained CD40 signals rescue B cells from CD95 killing. Here we
      describe a mechanism of early CD40-mediated rescue from CD95-induced apoptosis in
      B cells. Maximal rescue was achieved when CD40 signals were given within 1-2 h of
      initiating CD95 apoptosis. CD40 signaling did not block association of Fas
      associated death domain-containing protein with CD95, but decreased CD95-induced
      activation of caspases 3 and 8. Rapid CD40 rescue did not require NF-kappaB
      activation and was independent of de novo protein synthesis, but was dependent
      upon active PI3 K. Signaling via a CD40 mutant that does not bind TNFR-associated
      factor (TRAF)1, TRAF2, and TRAF3 rescued B cells from CD95-induced apoptosis.
      TRAF1/2/3-independent rescue was confirmed in B cell lines made deficient in
      these TRAF molecules by gene targeting. In contrast, CD40 rescue was completely
      abrogated in TRAF6-deficient B cells, which showed reduced activation of Akt in
      response to CD40 engagement. These results reveal a new rapid mechanism to
      balance B cell activation and apoptosis.

PMID- 16897815
TI  - Overexpression of ICAT highlights a role for catenin-mediated canonical Wnt
      signalling in early T cell development.
AB  - Transcription factors of the T cell factor/lymphoid enhancing factor (Tcf/Lef)
      family are key regulators in the development of T cell precursors to the CD4+8+
      stage. These factors are known targets of the canonical Wnt signalling pathway,
      and regulate transcription of Wnt target genes following interaction with the
      armadillo repeat-containing protein beta-catenin. However, as recent studies show
      normal thymocyte maturation in the absence of either beta-catenin or its
      homologue gamma-catenin, the role of Wnt signalling in Tcf/Lef activation during
      T cell development is controversial. To directly investigate the importance of
      catenin-mediated Wnt signalling in early thymocytes, we have compared the
      expression of beta- and gamma-catenin and analysed distinct stages of T cell
      precursor maturation following overexpression of inhibitor of beta-catenin and
      Tcf (ICAT), which inhibits Wnt signalling by preventing binding of armadillo
      repeat-containing proteins to Tcf/Lef. By direct retroviral gene targeting of CD4
      8- and CD4+8+ precursors, we show that ICAT overexpression inhibits the CD4-8--to
      CD4+8+ transition, but not the CD4+8+-to-CD4+8- or -CD4-8+ transition.
      Collectively, our data support a model in which canonical Wnt signalling
      influences T cell development in the thymus by playing an essential role in the
      maturation of CD4-8- but not CD4+8+ thymocytes.

PMID- 16897816
TI  - Human ILT2 receptor associates with murine MHC class I molecules in vivo and
      impairs T cell function.
AB  - Immunoglobulin-like transcript 2 (ILT2/LILRB1/LIR1/CD85j) is an inhibitory
      receptor broadly expressed on leukocytes and antigen-presenting cells that
      recognizes HLA-class I and human cytomegalovirus UL18 proteins. The function of
      this receptor is to generate negative signals or to inhibit positive signals.
      Here, we demonstrate the model to study the function of ILT2 in vivo using a
      newly generated transgenic mouse expressing the human inhibitory receptor on T,
      B, NK, and NKT cells. ILT2 expression affects thymocyte development and targets
      the proximal TCR signaling pathway, resulting in long-term survival or acceptance
      of skin allografts. The phenotype and constitutive tyrosine phosphorylation of
      ILT2 in transgenic mice illustrate the possible existence of a murine ligand. We
      report here that H-2Db, a murine MHC class I molecule, associates with human ILT2
      in vivo. This engagement with ILT2 directs effects on thymocyte development,
      negative regulation of TCR signaling, T cell activation, and alloimmune
      responses. Our finding provides support for an important inhibitory function of
      ILT2 in T cells in vivo and opens up strategies for targeting proximal TCR
      signaling for prevention of allograft rejection.

PMID- 16897817
TI  - Quantitative assessment of the gastrointestinal and cardiovascular risk-benefit
      of celecoxib compared to individual NSAIDs at the population level.
AB  - PURPOSE: To estimate the net cardiovascular (CV) (coronary heart disease, stroke,
      congestive heart failure), and gastrointestinal (GI) (peptic ulcer complications)
      risk-benefit public health impact of the use of celecoxib compared to non
      selective NSAIDs in the arthritis population. METHODS: We applied discrete event
      simulation models to data from the US National Health Surveys, CV risk-prediction
      models from the Framingham Heart Study, and population-based studies. Models took
      into account the multifactorial effect of risk factors, comorbidity, and
      competing risk of mortality. We simulated the natural history of CV and GI
      disease in the U.S. arthritis population over 1 year, through the individual
      baseline cardiovascular and gastrointestinal risk profile. This model was
      modified with relative risks associated with the use of each treatment. The mean
      number of events was estimated for each end-point in each model: natural history,
      celecoxib, diclofenac, ibuprofen, naproxen. The number of events for celecoxib
      was compared with each NSAID. RESULTS: The evaluation included 1% of the U.S.
      population with arthritis. Celecoxib, when applied to 100 000 patients over 1
      year, resulted in 570 (range from sensitivity analysis: 440-691), 226 (124-313),
      and 746 (612-868) fewer ulcer complications than diclofenac, ibuprofen, and
      naproxen, respectively. There were 20 (16-25), 8 (4-12), and 27 (22-32) fewer
      deaths from ulcer complications, respectively. No increase in cardiovascular
      events or all cause mortality was observed for celecoxib versus the other
      individual NSAIDs. CONCLUSION: Results from these simulations suggest a
      gastrointestinal benefit for celecoxib not offset by increased cardiovascular
      events or mortality. The methodology used here provides a risk-benefit assessment
      framework for evaluating the public heath impact of drugs.

PMID- 16897818
TI  - High-tech bioactives and novel enzymes from BRAIN, a European pioneer in white
      biotechnology.

PMID- 16897819
TI  - The impact of industrial biotechnology.
AB  - In this review, the impact of industrial (or "white") biotechnology can have on
      our society and economy is discussed. An overview is given of industrial
      biotechnology and its applications in a number of product categories ranging from
      food ingredients, vitamins, bio-colorants, solvents, plastics and biofuels. The
      use of fossil resources is compared with renewable resources as the preferred
      feedstock for industrial biotechnology. A brief discussion is also given of the
      expected changes in society and technology, ranging from the shift in the supply
      of resources, the growing need for efficiency and sustainability of the
      production systems, changing consumer perception and behaviour and changing
      agricultural systems and practices. Many of these changes are expected to speed
      up the transition from a fossil-based to a bio-based economy and society.

PMID- 16897820
TI  - The utilization of renewable resources in German industrial production.
AB  - Renewable resources will be an increasingly important issue for the chemical
      industry in the future. In the context of white biotechnology, they represent the
      intersection point of agriculture and the chemical industry. The scarcity and
      related increase in the price of fossil resources make renewable resources an
      interesting alternative. If one considers the production of bulk chemicals, it is
      evident that for this area besides the C sources, sugar and starch, new sources
      of raw materials must be opened up. One possible solution is to utilize
      lignocellulose both for materials and energy. This article discusses this
      interesting prospective for the future, particularly from the point of view of
      the German industry.

PMID- 16897821
TI  - White biotechnology: ready to partner and invest in.
AB  - It needs three factors to build an industry: market demand, product vision and
      capital. White biotechnology already produces high volume products such as feed
      additive amino acids and specialty products like enzymes for enantioselective
      biocatalysis. It serves large and diverse markets in the nutrition, wellness,
      pharmaceutical, agricultural and chemical industry. The total volume adds up to $
      50 billion worldwide. In spite of its proven track record, white biotechnology so
      far did not attract as much capital as red and even green biotechnology. However,
      the latest finance indicators confirm the continuously growing attractiveness of
      investment opportunities in white biotechnology. This article discusses white
      biotechnology's position and potential in the finance market and success factors.

PMID- 16897828
TI  - Metagenomics: an inexhaustible access to nature's diversity.
AB  - The chemical industry has an enormous need for innovation. To save resources,
      energy and time, currently more and more established chemical processes are being
      switched to biotechnological routes. This requires white biotechnology to
      discover and develop novel enzymes, biocatalysts and applications. Due to a
      limitation in the cultivability of microbes living in certain habitats,
      technologies have to be established which give access to the enormous resource of
      uncultivated microbial diversity. Metagenomics promises to provide new and
      diverse enzymes and biocatalysts as well as bioactive molecules and has the
      potential to make industrial biotechnology an economic, sustainable success.

PMID- 16897829
TI  - Optically active trans-2-aminocyclopentanols: chemoenzymatic preparation and
      application as chiral ligands.
AB  - Optically active trans-2-(N,N-dialkylamino)cyclopentanols and their acetates
      derivatives were obtained with very good chemical yields and enantiomeric
      excesses (95->/=99%), through a chemoenzymatic methodology based on the lipase
      catalyzed acylation of the hydroxyl group. The utility of these compounds was
      shown by the preparation of the cyclopentylic analog of vesamicol and by their
      use as ligands in the enantioselective addition of diethylzinc to benzaldehyde.

PMID- 16897836
TI  - Notification of retraction.

PMID- 16897838
TI  - Proceedings of the VI National Congress of the SITILO (Societa Italiana di
      Terapie Integrate Locoregionali in Oncologia), Rome, Italy, 26-28 November 2003.

PMID- 16897837
TI  - [Inquiries into local application of drugs on the inner ear. Innovation prize of
      the Working Group for German Speaking Audiologists and Neuro-otologists 2005].

PMID- 16897839
TI  - A woman with fever and rash after African safari.

PMID- 16897840
TI  - Epidural haematoma.

PMID- 16897841
TI  - Viewpoint: ICD cost-effectiveness.

PMID- 16897842
TI  - Practicing cardiology in a war zone.

PMID- 16897843
TI  - The development of echocardiography in Turkey.

PMID- 16897845
TI  - A simple trap.

PMID- 16897847
TI  - [An unusual case].

PMID- 16897848
TI  - The mass casualty situation affecting the USS Kitty Hawk.

PMID- 16897850
TI  - [Clinical significance of non-ACE-dependent angiotensin II-forming system].

PMID- 16897849
TI  - [Trends in hypertension research].

PMID- 16897851
TI  - [Significance of angiotensin II receptors].

PMID- 16897852
TI  - [Brain renin-angiotensin system].

PMID- 16897853
TI  - [Cell proliferation].

PMID- 16897854
TI  - [Stimulatory effects of angiotensin II on angiogenesis].

PMID- 16897855
TI  - [Acceleration of cellular senescence].

PMID- 16897856
TI  - [Sympathetic nervous system].

PMID- 16897857
TI  - [Adrenomedullin].

PMID- 16897859
TI  - [Ghrelin].

PMID- 16897858
TI  - [Role of AMP-activated protein kinase in the cardiovascular system].

PMID- 16897860
TI  - [TNF-alpha].

PMID- 16897862
TI  - [PPARgamma].

PMID- 16897861
TI  - [Homocysteine].

PMID- 16897863
TI  - [Rho and Rho-kinase].

PMID- 16897864
TI  - [Mechanical stress in cardiovascular remodeling].

PMID- 16897865
TI  - [Apoptosis of vascular cells].

PMID- 16897866
TI  - [Congenic strain for chromosome 1 quantitative trait locus for blood pressure].

PMID- 16897867
TI  - [Insulin-resistant hypertensive rats].

PMID- 16897868
TI  - [Hypertension in obese Zucker rat].

PMID- 16897869
TI  - [Failing heart of Dahl rat].

PMID- 16897871
TI  - [Salt hypertension in chimpanzees].

PMID- 16897870
TI  - [Genetically altered rodent models in the endothelin-related genes].

PMID- 16897872
TI  - [Genome scan in patients with hypertension].

PMID- 16897873
TI  - [Angiotensinogen gene].

PMID- 16897874
TI  - [alpha-Adducin gene].

PMID- 16897875
TI  - [Glucocorticoid receptor gene].

PMID- 16897876
TI  - [SLC12A3].

PMID- 16897877
TI  - [alpha-Adrenergic receptor gene].

PMID- 16897878
TI  - [Adrenomedullin gene].

PMID- 16897879
TI  - [Klotho gene].

PMID- 16897880
TI  - [Angiotensin II type 2 receptor gene].

PMID- 16897882
TI  - [Beyond BP lowering effect].

PMID- 16897881
TI  - [Pharmacogenomics for cardiovascular drugs].

PMID- 16897883
TI  - [Endothelial protection by angiotensin II type-1 receptor blockade].

PMID- 16897885
TI  - [Insulin sensitivity improving effect of ARB].

PMID- 16897884
TI  - [Antioxidant action and sympatho-inhibitory effect of ARB].

PMID- 16897886
TI  - [Cardioprotective effect of aldosterone antagonists for ventricular remodeling].

PMID- 16897887
TI  - [Effect of Ca blocker on heart failure].

PMID- 16897888
TI  - [Extracellular matrix proteins and glycoproteins in the cardiovascular system].

PMID- 16897889
TI  - Family-centred services in The Netherlands: validating a self-report measure for
      paediatric service providers.
AB  - OBJECTIVE: To validate the Dutch translation of the Canadian Measure of Processes
      of Care for Service Providers questionnaire (MPOC-SP) for use in paediatric
      rehabilitation settings in the Netherlands. DESIGN: The construct validity,
      content validity, face validity, and reliability of the Dutch MPOC-SP were
      determined. SUBJECTS: The 163 service providers that participated in the
      validation study represented seven children's rehabilitation centres and
      affiliated schools in the Netherlands (overall response rate 55.6%). In this
      sample 19 disciplines were represented. MAIN MEASURES: The MPOC-SP consists of 27
      items (assessing four domains) and was designed to examine how service providers
      think about the quality of care they provide and to assess the extent to which
      these services are family centred. Fifty-three service providers filled out an
      additional face validity questionnaire. RESULTS: All items correlated best and
      significantly with their own scale score (r(s) 0.48-0.82, P<0.001). The Pearson's
      correlation coefficients were all significant and confirmed that the four scales
      measure different aspects of a same construct, namely family-centred service. The
      content validity and the face validity of the Dutch MPOC-SP were good, indicating
      the questionnaire measures relevant aspects of family-centred service delivery in
      paediatric rehabilitation settings in the Netherlands. The test-retest analyses
      (intraclass correlation coefficient (ICC) 0.83-0.89) and the internal consistency
      analyses (alpha 0.65-0.84) showed that the Dutch MPOC-SP is a reliable tool.
      CONCLUSIONS: The Dutch MPOC-SP is a reliable and valid instrument to measure the
      family-centredness of service delivery.

PMID- 16897891
TI  - [Dyslipidemia after intensive physical exercise and atherosclerosis: is there a
      correlation?].

PMID- 16897892
TI  - Vast majority opposed to badger culling.

PMID- 16897893
TI  - Equine disease surveillance, January to March 2006.

PMID- 16897894
TI  - Genetic engineering of embryonic stem cells.
AB  - We describe a novel generation of lentiviral vectors that are particularly well
      suited for work with embryonic stem cells. The possibility of selecting cell
      lines with antibiotics and the rapid insertion of any combination of promoters
      and genes of interest makes them a powerful tool in the generation of transgenic
      ES cell lines. This vector can also greatly facilitate studies aimed at the
      improvement of neuronal engineering from ES cells, by making it possible to
      monitor the emergence and differentiation of neurons.

PMID- 16897895
TI  - Controversy exists on the use of carbon dioxide (CO2) for the euthanasia of
      rodents.

PMID- 16897896
TI  - [Economic or medical innovations: that is the question!].

PMID- 16897897
TI  - What do insurance claims really cost?

PMID- 16897898
TI  - An ugly picture for flower workers and their children.

PMID- 16897899
TI  - Gene-environment studies: who, how, when, and where?

PMID- 16897900
TI  - Flagging environmental health awareness on beaches.

PMID- 16897901
TI  - Use of a PCR assay for diagnosing African trypanosomiasis of the CNS: a case
      report.

PMID- 16897902
TI  - Medicare and state health care programs: fraud and abuse; safe harbors for
      certain electronic prescribing and electronic health records arrangements under
      the anti-kickback statute. Final rule.
AB  - As required by the Medicare Prescription Drug, Improvement, and Modernization Act
      of 2003 (MMA), Public Law 108-173, this final rule establishes a new safe harbor
      under the Federal anti-kickback statute for certain arrangements involving the
      provision of electronic prescribing technology. Specifically, the safe harbor
      would protect certain arrangements involving hospitals, group practices, and
      prescription drug plan (PDP) sponsors and Medicare Advantage (MA) organizations
      that provide to specified recipients certain nonmonetary remuneration in the form
      of hardware, software, or information technology and training services necessary
      and used solely to receive and transmit electronic prescription information. In
      addition, in accordance with section 1128B(b)(3)(E) of the Social Security Act
      (the Act), this final rule creates a separate new safe harbor for certain
      arrangements involving the provision of nonmonetary remuneration in the form of
      electronic health records software or information technology and training
      services necessary and used predominantly to create, maintain, transmit, or
      receive electronic health records.

PMID- 16897903
TI  - Medicare program; physicians referrals to health care entities with which they
      have financial relationships; exceptions for certain electronic prescribing and
      electronic health records arrangements. Final rule.
AB  - As required by section 101 of the Medicare Prescription Drug, Improvement, and
      Modernization Act of 2003 (MMA), this final rule creates an exception to the
      physician self-referral prohibition in section 1877 of the Social Security Act
      (the Act) for certain arrangements in which a physician receives compensation in
      the form of items or services (not including cash or cash equivalents)
      ("nonmonetary remuneration"') that is necessary and used solely to receive and
      transmit electronic prescription information. In addition, using our separate
      legal authority under section 1877(b)(4) of the Act, this rule creates a separate
      regulatory exception for certain arrangements involving the provision of
      nonmonetary remuneration in the form of electronic health records software or
      information technology and training services necessary and used predominantly to
      create, maintain, transmit, or receive electronic health records. These
      exceptions are consistent with the President's goal of achieving widespread
      adoption of interoperable electronic health records to improve the quality and
      efficiency of health care while maintaining the levels of security and privacy
      that consumers expect.

PMID- 16897905
TI  - Motivators for children with severe intellectual disabilities in the self
      contained classroom: a movement analysis.
AB  - The purpose of this study was to analyze the impact of the presence of a music
      therapist versus the use of switch-activated toys and recorded music in evoking
      physiological, affective, and vocal responses in school-aged children who are
      considered SID, or Severely Intellectually Disabled. Researchers studied movement
      responses to determine how these children might respond more readily to a music
      therapist interacting musically with them than to the toys and to the recorded
      music. Each of the 17 children participated in a videotaped session that included
      5 trials. Other than the rest trial, motivators presented were: a switch
      activated pig toy, switch-activated recorded music, the music therapist playing
      and singing to the child contingent upon his touching the guitar, and the
      therapist playing and singing to the child continually. A data collection sheet
      was developed by the researchers to assess positive responses by measuring limb
      and head movement, vocal sound, and facial expression change. The Kruskal-Wallis
      test was used to determine differences in means responses to music and nonmusic
      trials. At a 90% level of confidence, statistical significance was attained in
      comparing the responses to the pig toy, recorded music, and "activated guitar"
      trial to the trial during which the therapist played guitar and sang continually
      to the child. In addition, at a 95% level of confidence, statistically
      significant differences were found in comparing the pig and the recorded music
      trials with the therapist trial.

PMID- 16897904
TI  - Psychiatric patients' perception of music therapy and other psychoeducational
      programming.
AB  - The purpose of this study was to quantitatively evaluate psychiatric patients'
      perception of their psychoeducational programming. Participants (N = 73)
      completed a survey rating on each class/therapy in which they were enrolled and
      its helpfulness. Participants answered questions concerning which class/therapy
      addressed specific psychiatric deficit areas most effectively. Results indicated
      that participants rated music therapy as significantly more helpful than all
      other programming (p < .05). Further analyses indicated that participants
      admitted to a psychiatric institution only once rated their classes as more
      helpful when compared to participants who had been admitted multiple times.
      Additionally, participants who were minorities rated programming as more helpful
      than participants who were Caucasian. Participants consistently rated music
      therapy as more effective than other programming in addressing specific
      psychiatric deficit areas. Additionally, 57% of participants noted that music
      therapy was their favorite class/therapy. Reasons for these discrepancies are
      discussed and suggestions for future research are made.

PMID- 16897906
TI  - The effects of music therapy on pediatric patients' pain and anxiety during donor
      site dressing change.
AB  - The purpose of this study was to assess the effects of music therapy on pain and
      anxiety in pediatric burn patients during a donor site dressing change. Fourteen
      subjects were randomly selected to participate in this study. The experiment was
      conducted in the Reconstructive Unit of Shriners Burns Hospital-Boston. The
      experimental group's intervention consisted of live music and was compared to a
      control group whose intervention was verbal interaction. Psychological,
      behavioral, and physiological data were assessed through the Wong Baker FACES
      Pain Rating Scale, the Fear Thermometer, the Nursing Assessment of Pain Index,
      heart rate, and respiration rate. Data were analyzed using the ANCOVA, Mann
      Whitney U, and regression analysis. The results were mixed and inconclusive. The
      members of the experimental group reported anecdotal information about the
      effects of music on pain and anxiety. An exploration of the limitations of the
      study and suggestions for further study are discussed.

PMID- 16897907
TI  - The effect of rhythmic auditory stimulation (RAS) on gait characteristics of
      cadence, velocity, and stride length in persons with late stage dementia.
AB  - Persons (N = 28) diagnosed with dementia in late stage who had locomotion
      Functional Independence Measure (FIM) ratings of l, total assistance required,
      and 2, maximal assistance required, participated as subjects. All participants
      were enrolled in a restorative ambulation program which was implemented in this
      study under 3 conditions: Rhythmic auditory stimulation in which metronomic beats
      were imbedded in music, rhythmic auditory stimulation which consisted of
      metronomic beats without music, and no auditory stimulus. Gait characteristics of
      cadence, velocity, and stride length were compared across the 3 conditions. No
      statistically significant differences were found, however, observation showed
      that assistive burden seemed less when both forms of rhythmic auditory
      stimulation were used. Further research is recommended to study the effects of
      RAS on care burden and continued ambulation throughout the disease trajectory.

PMID- 16897908
TI  - Estimates of HIV prevalence and incidence in Canada, 2005.

PMID- 16897909
TI  - Meta-research on violence and victims: the impact of data collection methods on
      findings and participants.

PMID- 16897910
TI  - Participant responses to retrospective surveys of child maltreatment: does mode
      of assessment matter?
AB  - This study examines the impact that different methods of assessing child
      maltreatment history may have on adult participants. A total of 334 female
      undergraduate students were randomly assigned to complete a retrospective measure
      of child sexual and physical abuse in one of three conditions: paper-and-pencil
      questionnaire, face-to-face interview, or computer-administered survey.
      Disclosure rates of abuse, psychological distress and mood change, preferences
      for assessment format, and perceptions of confidentiality were examined across
      the three assessment formats. Although disclosure did not vary by condition,
      participants with a history of abuse reported more distress and mood change than
      did nonvictims, particularly in the computer condition. Nevertheless, the
      computer condition was rated as the most preferred format and was viewed by
      participants as the most confidential means of assessing maltreatment history.
      Participants reporting abuse through interviews were more likely than those in
      other conditions to state a preference for another type of assessment format. The
      implications of these findings for abuse history research are discussed.

PMID- 16897911
TI  - Sensitive research with adolescents: just how upsetting are self-report surveys
      anyway?
AB  - Distress related to answering personal survey questions about drug use, suicidal
      behavior, and physical and sexual abuse were examined in multiple convenience
      samples of adolescents. Samples varied in consent procedures utilized (active vs.
      passive parental consent), data collection setting (school vs. juvenile justice),
      developmental level (middle school vs. high school). Participation rates differed
      across consent procedures (e.g., 93% with passive vs. 62% with active parental
      consent). Results indicated that small percentages of adolescents in every sample
      reported frequently feeling upset while completing the survey (range 2.5% to
      7.6%). Age, race, gender, and data collection strategy did not emerge as
      significant predictors of feeling upset. Instead, as hypothesized, adolescents
      reporting a history of suicidal ideation or attempt, illicit drug use, or
      experiences of physical or sexual victimization endorsed more frequent feelings
      of upset while completing the survey than peers without these experiences. Taken
      together, however, these sensitive event experiences explained only 6.6% of the
      variance in adolescents' upset ratings. The scientific and ethical implications
      of these findings are discussed with regard to adolescent participation in survey
      research about sensitive topics.

PMID- 16897912
TI  - Telephone survey respondents' reactions to questions regarding interpersonal
      violence.
AB  - Concerns have been raised regarding the appropriateness of asking about violence
      victimization in telephone interviews and whether asking such questions increases
      respondents' distress or risk for harm. However, no large-scale studies have
      evaluated the impact of asking such questions during a telephone interview. This
      study explored respondents' reactions to questions regarding violence in two
      large recently completed telephone surveys. After respondents were asked about
      violence, they were asked if they thought surveys should ask such questions and
      whether they felt upset or afraid because of the questions. In both surveys, the
      majority of respondents (regardless of their victimization history) were willing
      to answer questions about violence and were not upset or afraid because of the
      questions. More than 92% of respondents thought such questions should be asked.
      These results challenge commonly held beliefs and assumptions and provide some
      assurance to those concerned with the ethical collection of data on violent
      victimization.

PMID- 16897913
TI  - A comparison of methods for collecting self-report data on sensitive topics.
AB  - Insufficient attention has been paid to whether disclosure rates of sensitive or
      stigmatizing information vary as a function of method of inquiry. Methods vary
      both in terms of the anonymity afforded the participant and the opportunity to
      make a connection with the researcher, both of which might affect participants'
      willingness to disclose such information. In this investigation, 215
      undergraduate students were randomly assigned to complete identical
      questionnaires using one of the three most common methods of data collection (in
      person interview, telephone interview, and paper-and-pencil questionnaire) or an
      automated telephonic data collection (ATDC) system. Questions on six topic areas
      of increasing social sensitivity (study habits, substance use, physical and
      sexual aggression, victimization and perpetration) were included. The results
      indicated that there were no differences in disclosure rates due to methods and
      no method by topic interaction, but the two telephonic methods both produced
      significantly higher participation rates than the two other methods. The results
      suggest that, at least for a college student sample, an automated telephonic
      system produces data comparable to that of more traditional methods, while
      offering greater convenience, economy, and participation.

PMID- 16897914
TI  - Sexual assault survivors' reactions to a thought suppression paradigm.
AB  - Trauma survivors may experience harm from participating in research on sensitive
      topics. The current study assessed reactions of sexual assault survivors with and
      without symptoms of post-traumatic stress disorder (PTSD) immediately following
      an experimental thought suppression task and at a 2- to 4-week follow-up period,
      by asking open-ended questions regarding thoughts about the experiment, feelings
      following the experiment, and willingness to participate in similar experiments.
      At both time periods, most participants reported neutral/positive thoughts (e.g.,
      "interesting") and feelings (e.g., "fine, good") and indicated that they would
      participate in a similar study. Findings suggest that the majority of sexual
      assault survivors were not harmed in the short- or long-term by participation in
      a thought suppression paradigm in which the target of suppression/expression was
      their own trauma.

PMID- 16897915
TI  - The risk of partner aggression research: impact of laboratory couples conflict
      protocols on participants.
AB  - The impact of male-to-female intimate partner violence (IPV) research on
      participants is unknown. A measure of impact was given to participants in an IPV
      study to assess systematically the impact of completing questionnaires, engaging
      in conflict conversations, and being interviewed individually about anger
      escalation and de-escalation during the conversations. Participants completed a
      six-question, Likert-scaled impact measure. Both male and female participants
      rated the impact of the study as helpful to them personally and to their
      relationships. Female participants rated different segments of the study as more
      helpful to themselves and their relationships, while male participants did not
      find any segment of the study to have a different impact than other segments.

PMID- 16897917
TI  - Does questionnaire format impact reported partner violence rates?: An
      experimental study.
AB  - Researchers assess partner violence using numerous formats, but whether
      questionnaire format affects obtained rates has rarely been examined. We compared
      paper-and-pencil versus computer administrations, and standard Revised Conflict
      Tactics Scales (CTS2) categories versus dichotomous (yes/no) response categories,
      in a 2 x 2 experiment with 160 undergraduate students. Differential validity was
      also examined for gender. Results provide some support for the use of all
      formats, although sexual coercion rates showed more measurement variability than
      reports of psychological aggression, physical assault, or injury. Sexual coercion
      effects also differed by gender. The standard CTS2 categories resulted in more
      disclosures than dichotomous categories for some variables. Differences between
      computer and paper-and-pencil formats were generally minimal. More attention to
      the effects of questionnaire design on disclosures of violence is urgently
      needed.

PMID- 16897916
TI  - Effects of method on participants and disclosure rates in research on sensitive
      topics.
AB  - This study replicates and extends the research of Rosenbaum, Rabenhorst, Reddy,
      Fleming, and Howells, which also appears in this special issue. Responses from
      398 randomly assigned participants regarding differentially sensitive topics were
      collected via four methods of data collection: written questionnaires, face-to
      face interviews, telephone interviews, and an automated telephonic data
      collection system (ATDC). Several significant differences in data collection
      methodology and topic area were found, including greater disclosure of sensitive
      information via the ATDC system than via face-to-face and paper-and-pencil
      conditions. Participants who were assigned to the ATDC condition felt
      significantly more comfortable answering questions compared to those in the face
      to-face interview condition. Participants in the telephone interview condition
      reported answering significantly more carefully than participants answering via
      written questionnaire. Taken together, the results of this study and the previous
      one it replicates suggest that the ATDC produces disclosure rates that are at
      least equivalent to, if not greater than, those generated using traditional
      methods for collecting sensitive data.

PMID- 16897918
TI  - Reaction time and item presentation factors in the self-report of partner
      aggression.
AB  - The Conflict Tactics Scales (CTS) have used different formats intended to
      maximize the accuracy and disclosure of relationship aggression. The original CTS
      presented items in a hierarchical order, seeking to establish a "context of
      legitimation." The CTS2 presented items in an interspersed order to reduce denial
      response sets. The current study used computer administration of the CTS and
      sought to determine whether the two presentation formats described above result
      in differing self-reports of aggression and to explore possible causes of such an
      effect, such as differences in reaction time. Results indicated that item order
      did not significantly affect reports of aggression, but increasing participants'
      reaction times by experimental manipulation of the minimum item display duration
      resulted in increased self-reports of aggression.

PMID- 16897920
TI  - Atrial fibrillation: a symptom treated as a disease?

PMID- 16897919
TI  - How do I tell thee? Voice, pen, or computer key.
AB  - In this issue, the previous two articles by Hamby and colleagues and Vega and
      O'Leary are concerned with whether the method of administration and format of the
      Conflict Tactics Scale influence participant responses. Because they examine
      different aspects of the same measure, I was asked to conclude the issue by
      writing a brief summary and integration of the two articles.

PMID- 16897921
TI  - Seven plus one reasons for surveys of acute myocardial infarction in Greece.

PMID- 16897922
TI  - Cardiac resynchronization therapy decreases the mitral coaptation point
      displacement in heart failure patients.
AB  - BACKGROUND: In patients with left ventricular (LV) dysfunction the mitral leaflet
      coaptation point (CPMA) is displaced towards the LV apex. The aim of our study
      was to estimate the value of CPMA measurement as a simple index regarding the
      acute effects of cardiac resynchronization therapy (CRT), which is coming to be
      an established method of treatment for congestive heart failure (CHF). METHODS:
      We studied 20 patients with CHF (NYHA III-IV) and LV ejection fraction (LVEF) 22
      +/- 4%. All patients received CRT and an echocardiogram was performed within 24
      48 hours. The echocardiographic indices LV end-diastolic diameter (LVEDD) and end
      systolic diameter (LVESD), LVEF, mitral annulus diameter (MAD), and the degree of
      intraventricular desynchronization, were measured at CRT off and CRT on. The
      CPMA, the distance between the coaptation point of the mitral leaflets and the
      mitral annulus, was measured from the apical 4-chamber view in end-systole at
      both CRT on and CRT off. RESULTS: CRT improved both the contractility and
      dimensional indices in CHF patients. CPMA decreased from 11.3 +/- 2 mm at CRT off
      to 9.1 +/- 1.8 mm after CRT on (p < 0.001) and MAD from 38.9 +/- 3.9 mm at CRT
      off to 37.5 +/- 3.7 mm at CRT on (p < 0.002). LVEF improved from 24.5 +/- 5.7% at
      CRT off to 29.5 +/- 5.1% at CRT on (p < 0.001). There was an improvement in LV
      synchronization from 88 +/- 7 ms at CRT off to 48 +/- 3 ms at CRT on (p < .001).
      CPMA was correlated with MAD (r = 0.52, p < 0.05 and r = 0.59, p < 0.05 at CRT
      off and CRT on, respectively). Moreover, the absolute change in CPMA was
      correlated with LVESD (r = 0.68) and LVEDD (r = 0.65), both p < 0.05, with the
      time difference of the basal segments of the septal and lateral wall at CRT on (r
      = 0.68, p < 0.01), and inversely correlated with LVEF (r = -0.55, p < 0.05).
      CONCLUSION: In patients with severe LV systolic dysfunction and dilatation CRT
      was associated with an improvement in both CPMA and MAD.

PMID- 16897923
TI  - Anastomoses between bronchial and coronary circulation in a porcine model:
      computed tomographic and angiographic demonstration.
AB  - INTRODUCTION: Although the importance of the bronchial arteries is evident in
      modern day thoracic surgery, the significance of their communications with
      coronary arteries has yet to be appreciated, especially in cases of heart-lung
      transplantation and aortic aneurysm repair. We conducted a study to demonstrate
      the coronary-bronchial anastomotic routes in a porcine model using angiography
      and computed tomography. METHODS: Six young female white pigs were used. The
      heart and lungs were removed en bloc, including the lower trachea and oesophagus.
      Digital subtraction angiography of the bronchial circulation and spiral computed
      tomography scan were performed in a three-phase study before and after
      administration of contrast medium. This was achieved by infusion either into the
      cannulated bronchial artery or into the aortic root. Macroscopic evaluation was
      carried out using latex infusion into the bronchial or coronary circulation.
      RESULTS: We demonstrated communications between the bronchial and coronary
      systems in 5 of 6 subjects. This communication was located at the left atrial
      wall and the posterior and anterior wall of the left ventricle. In one case there
      were further anastomoses around the right atrial wall. CONCLUSIONS: There were
      communications between the left coronary arteries and the bronchial arteries in
      the majority of cases. Digital subtraction angiography and spiral computer
      tomography scan can demonstrate these communications directly and indirectly by
      measurements of contrast enhancement within the heart wall. Our study emphasises
      the importance of the bronchial arteries in cases of heart-lung transplantation
      and repair of thoracic aortic aneurysms.

PMID- 16897924
TI  - Proarrhythmic effects of atrial fibrillation ablation techniques.
AB  - BACKGROUND: The incidence of proarrhythmia induced by ablation for atrial
      fibrillation (AF) is not entirely known. We describe the incidence and management
      of atrial arrhythmias occurring after various techniques for the ablative therapy
      of AF. METHODS: Ninety-four patients with paroxysmal AF underwent ostial
      pulmonary vein (PV) ablation (n=54) or circumferential ablation around the PV
      ostia (n=40). RESULTS: Atrial tachycardia or flutter was detected during the
      first 6 months after AF ablation in 10 patients. Atrial arrhythmia was more
      common among patients who underwent circumferential ablation or circumferential
      with lines (18.2% and 22.2%, respectively) than in those who were treated with
      other techniques (p = 0.037). The incidence of atrial tachycardia or flutter
      among patients who underwent ostial ablation or ostial with lines was 2.4% and
      8.3%, respectively. No difference was observed in the risk of atrial arrhythmia
      between patients who underwent ablation with or without additional lines, either
      ostial (p = 0.398) or circumferential (p = 0.999). Re-ablation was performed in 7
      patients with sustained atrial arrhythmia. At 6 months, no recurrence of atrial
      tachycardia or flutter was.seen in 6 of these patients, nor in 3 patients with
      non-sustained atrial tachycardia or flutter. CONCLUSIONS: The incidence of atrial
      tachycardia or flutter following AF ablation is lower for ostial than for
      circumferential ablation. The addition of lines along the mitral isthmus and
      between the superior PVs does not significantly affect the risk of ablation
      induced arrhythmia. Non-sustained atrial tachycardia or flutter during or early
      after AF ablation procedures does not require additional ablation.

PMID- 16897925
TI  - The influence of thrombolytic therapy on C-reactive protein in ST-segment
      elevation acute myocardial infarction.
AB  - BACKGROUND: Inflammation plays a crucial role in atherosclerotic processes and in
      acute coronary syndromes (ACS). Strong evidence of this is the elevation of C
      reactive protein (CRP) serum levels during an ACS and its short- and long-term
      prognostic potency. The present study aimed to assess the relation between CRP
      serum levels and the elevation of cardiac markers in patients with ST elevation
      acute myocardial infarction (STEMI) as well as the effect of intravenous
      thrombolysis on a time series of CRP values. METHODS: Thirty-six patients with
      STEMI were enrolled in the study. Twenty-eight of them received intravenous
      thrombolysis successfully and 8 did not receive thrombolysis. We measured serum
      concentrations of CRP, troponin I, creatine kinase, creatine kinase isoenzyme and
      lactate dehydrogenase in all patients on admission, 24 and 48 hours later. CRP
      serum values were obtained using the turbidimetric method. Coronary angiography
      was performed in all patients to estimate disease severity and culprit vessel
      flow after treatment. RESULTS: Patients who were thrombolysed had lower CRP
      values on admission (p < 0.05), at 24 hours (p < 0.001) and 48 hours later (p <
      0.05), compared to those without thrombolysis. CRP values on admission had a
      positive correlation with markers of cardiac myocyte necrosis and a negative
      correlation with TIMI flow. CONCLUSION: Thrombolytic therapy in patients with
      STEMI is associated with a less pronounced response of CRP during the first 48
      hours. The close relation of CRP with cardiac enzymes and troponin I on admission
      adds to the proven value of this inflammatory marker and suggests directions for
      further research.

PMID- 16897926
TI  - Beneficial effects of omega-3 fatty acids: the current evidence.

PMID- 16897927
TI  - Masked hypertension: a new entity under investigation.

PMID- 16897928
TI  - Partial anomalous pulmonary venous connection.

PMID- 16897929
TI  - Inspiratory muscle training in a patient with left ventricular assist device.
AB  - The use of mechanical assist devices as a 'bridge' to cardiac transplantation, as
      a "bridge" to recovery, or as a destination therapy in end-stage heart failure,
      is increasing. Studies of different modes of rehabilitation in this population
      are lacking. We report the benefits of inspiratory muscle training on the
      exercise capacity and quality of life in the recipient of a left ventricular
      assist device.

PMID- 16897930
TI  - Cardiogenic shock due to isolated right ventricular infarction in an elderly
      woman.
AB  - A 78-year-old hypertensive woman with no prior history of ischemic heart disease
      arrived at the hospital complaining of weakness and profound fatigue. Four days
      earlier, she had experienced substernal chest pain associated with nausea and
      vomiting. A standard 12-lead electrocardiogram showed marked ST-segment elevation
      and negative T waves in leads V1 and V2. The patient was treated with anti
      thrombotic therapy, dobutamine and dopamine infusions. Angiography showed
      proximal occlusion of a small, non-dominant right coronary artery and no
      clinically significant disease in the left coronary artery. Isolated right
      ventricular infarction accounted for the cardiogenic shock in this elderly
      patient. She received conservative medical treatment and was discharged in good
      condition.

PMID- 16897931
TI  - Emergency surgery for embolisation of Amplatzer device into the left atrium.
AB  - Occlusion of secundum atrial septal defects (ASD) by means of percutaneous
      transcatheter systems is increasingly used in clinical practice. A variety of
      different types and models of septal occluder devices are available nowadays,
      amongst which the Amplatzer device (Amplatzer Medical, Golden Valley, MN,
      U.S.A.), is regarded as one of increasing popularity. We report a case of
      attempted percutaneous transcatheter closure of a large ASD in an 11-year-old
      boy, complicated by device embolisation to the left atrium necessitating
      emergency surgery.

PMID- 16897932
TI  - Stenting of a stenotic aortic homograft in pulmonary position after the Ross
      procedure.
AB  - Pulmonary autograft replacement of the aortic valve (Ross procedure) has
      potential advantages, with favorable rates of survival and freedom from
      reoperation. The procedure itself, however, involves insertion of a homograft in
      the pulmonary position. The development of severe homograft stenosis is an
      uncommon but clinically important complication. We report the case of a young
      female who developed a symptomatic homograft stenosis a year after she underwent
      the Ross procedure. The lesion was stented successfully and the homograft's
      patency, together with a markedly improved pressure gradient, was still
      maintained eight months after percutaneous stenting.

PMID- 16897933
TI  - The physician and the physician scientist.

PMID- 16897934
TI  - Modernisation of scientific institutions: an urgent need for viability and
      progress.

PMID- 16897937
TI  - Revisiting case study as a nursing research design.
AB  - Case study research provides nurses with a form of inquiry that is holistic and
      appropriate for a variety of populations. Jeanine Gangeness and Eleanor Yurkovich
      discuss components of case study research, including its theoretical base, design
      methods, multiple data sources and analysis. The information presented is
      expanded on by using a planned population-based, multiple-case explanatory study.

PMID- 16897938
TI  - Qualitative interviewing: encountering ethical issues and challenges.
AB  - This article, in which Amanda Clarke recounts her own experiences as a novice
      researcher, explores the ways in which research can affect participants. The
      author argues that researchers must be mindful of the impact their questioning
      can have on subjects, especially those who are vulnerable, and suggests that a
      reflexive approach can help minimise the risk of harmful effects.

PMID- 16897940
TI  - Exploration of nurses' information environment.
AB  - Elaine Ballard's article focuses on health informatics, a field which has
      developed with limited input from nurses who provide direct care.

PMID- 16897939
TI  - Experiencing nursing education research: narrative inquiry and interpretive
      phenomenology.
AB  - Narrative inquiry is emerging from higher education curriculum studies into
      nursing, and interpretive phenomenology is established in nursing education
      research. These two research methods are compared by subject matter, agent,
      method, data and outcome, using examples from nursing education research. This
      comparison facilitates a researcher's choice of method by showing what is
      revealed by each type of inquiry and how they differ.

PMID- 16897942
TI  - 'To me, all registered nurses are of an equal standing'.

PMID- 16897941
TI  - Presenting research to clinicians: strategies for writing about research
      findings.
AB  - Research is of little value to clinical practice if the findings are not
      appropriately integrated into that practice. While publishing the results of
      research is essential for translating findings into practice, Marilyn Oermann and
      colleagues suggest that work is not done until the findings are disseminated for
      use by clinicians and others who need the research results to guide their
      practice

PMID- 16897943
TI  - Scholarship in nursing: what really counts?

PMID- 16897944
TI  - Trichomonas vaginalis in Turkey--a review.

PMID- 16897945
TI  - [Prevalence of Trichomonas vaginalis Donne in women of Lodz population in 1955
      1999 years].
AB  - Search for Trichomonas vaginalis was carried out in direct (in 0.85% NaCl and
      0.1% safranine) and fixed stained microscopical preparations ( Wright or Giemsa
      methods, after fixation with 70% methyl alcohol) and cultures ( Pavlova, Johanson
      Trussel-John, Roiron-Ratner, Simic media), from materials of the vagina, urethra
      and cervix uteri. In the years 1955-1999 a total of about 12000 women were
      examined. The prevalence of T. vaginalis in women population of Lodz region was
      high (from 26.6% still 78.0%); on the last ten years in about half of the sample
      examined women were infected of T. vaginalis.

PMID- 16897946
TI  - [Hydrolytic activity of Trichomonas vaginalis Donne strains].
AB  - The hydrolytic activity of Trichomonas vaginalis Donne strains was investigated
      using API ZYM test (bioMerieux). Among 19 determined hydrolases were found
      alkaline and acid phosphatases; also in several strains N-acetyl-beta
      glucosaminidase and a-glucosidase were demonstrated. The API ZYM test may be used
      for characterization of enzymatic activity of T. vaginalis strains, but adequate
      medium is necessary.

PMID- 16897947
TI  - The epidemiology of toxoplasmosis in Turkey--a review of the literature.
AB  - Turkish literature published between 1980-2000 were reviewed from the point of
      the epidemiology of toxoplasmosis in Turkey. The data obtained from this review
      were collected at five different tables: 1. Hospital patients, 2. People who had
      close contact with animals or working in meat industry, 3. Apparently healthy
      people, 4. Special groups such as homosexuals, hemodialysis patients, and 5. The
      prevalence in animals of live-stocks and domestic animals. The prevalence rates
      in these groups were as follows: 13.9% -85.3%; 20.7% -57.6%; 23.0% -43.7%; 16.3% 
      76.6%; 39.5% -78.0%. The role of meat eating habits of people and living in
      close contact with cats were emphasized on these high rates.

PMID- 16897948
TI  - Toxoplasmosis in neurologic patients.

PMID- 16897950
TI  - Serodiagnostics of Toxoplasma gondii invasions.
AB  - Diagnosis of T. gondii invasions is based mainly on serological tests, because of
      their relative simplicity and availability. In the present work we examined
      efficiency of immunoblot and two inhouse ELISA assays in anti-Toxoplasma antibody
      detection, comparing our results with those obtained using commercial ELISA kit
      of Organon Teknika. We found that inhouse ELISAs and immunoblot can be helpful in
      diagnosing toxoplasmosis.

PMID- 16897949
TI  - [Analysis of the local synthesis of Toxoplasma gondii-specific immunoglobulins in
      the anterior eye chamber fluid. Report of two cases].
AB  - We reported two cases strongly suspected of ocular toxoplasmosis, in which a
      puncture of anterior eye chamber was performed for a final verification of
      clinical diagnosis. In both patients, fresh focal lesions of retinochoroiditis
      associated with old pigmented retinal scars were diagnosed. The 62-year-old women
      had a serological evidence of recently acquired T. gondii infection with an
      increasing IgG titre of a low avidity and a presence of specific IgM and IgA
      antibodies. In the 13-year-old girl, an immunological profile of the chronic
      infection was shown, confirmed by a high IgG avidity value. In the patient with a
      clinical picture of recurrent congenital toxoplasmosis, intraocular production of
      T. gondii-specific IgG was found in anterior eye chamber. The analysis of the
      specific antibodies synthesis in ocular fluid by the Western blot seems to be a
      valuable immunodiagnostic method for a final diagnosis of ocular toxoplasmosis.

PMID- 16897951
TI  - [Peripheral blood lymphocytes T gammadelta in children with acute acquired
      toxoplasmosis].
AB  - The aim of the study was to determine the percentage participation of lymphocytes
      CD3TCRgammadelta in peripheral blood of children with acute toxoplasmosis. The
      study compromised 30 children aged 2-14 years. Increase of the percentage of
      CD3TCR gammadelta cells was observed in the group of children with clinical
      symptoms of toxoplasmosis (mean value 5.7%) in relation to the comparative group
      (mean 4.4%), but in 12 children (40%) the mean value was 8.1%. Toxoplasma gondii
      infection produces a strong signal for activation of cells with gammadelta
      receptors. Examination of CD3TCRgammadelta cells may be helpful in the diagnosis
      of the acute phase of T. gondii infection.

PMID- 16897952
TI  - [Congenital toxoplasmosis in own studies].
AB  - Clinical picture of congenital Toxoplasma gondii has been presented in 20
      children. The infection was diagnosed in 18 children in the first and in 2
      children in the sixth month of life. Clinical symptoms were observed in as many
      as 12 children. The most frequent symptoms were those concerning central nervous
      system, organ of vision in the form of hydrocephalus, spastic paresis, epilepsy,
      intracranial calcification, choroiditis, retinitis and vision impairment. The
      presented analysis indicates an urgent need of introduction of screening in
      pregnant women and infants and widespreading of prophylactic activity aiming at
      raising awareness of the existing threat of T. gondii infection.

PMID- 16897953
TI  - [Evaluation of the usefulness of serological examinations in the prophylaxis of
      congenital toxoplasmosis in the materials of CM UJ Parasitology Department].
AB  - A total of 9661 persons, mainly from southern region of Poland, were tested by
      using Sabin-Feldman dye test and ELISA test to determine the IgG class in the
      years 1991-2000. The tests were positive in 5297 persons (54.8%). The study
      included 320 pregnant women: 141 with low and mean titres of IgG class
      antibodies: 8-300 UM/ml and 62 with high titres, exceeding 300 UM/ml, who were
      tested only once. There were 117 seronegative pregnant women; the test was
      performed only once in 108 of them and twice in 9. The test was not repeated
      third time in any women of this group. According to the guidelines of congenital
      toxoplasmosis prophylaxis, the tests do not meet the expectations.

PMID- 16897954
TI  - [Use of the PCR technique for diagnosis of symptomatic congenital toxoplasmosis
      based on own observations].
AB  - The aim of our study was to determine the usefulness of PCR technique in
      postnatal diagnosis of congenital toxoplasmosis in 17 infants aged from 1 week to
      10 months. In 13 cases the diagnosis was established. The diagnostic procedures
      involved: clinical examinations, serological tests, nested-PCR method and
      neuroimaging examinations. RESULTS: In almost all children (except one) a high
      level of toxoplasmatic IgG antibodies was found; in 1/3 we identified antibodies
      IgM and IgA. In 14 cases the PCR test from CSF was positive. In 4 infants the
      suspicion of congenital toxoplasmosis was ruled out; in 2 of them PCR from CSF
      was negative, in 2 - a false positive result was stated. CONCLUSIONS: PCR is a
      valuable technique for diagnosis of congenital toxoplasmosis. Because of the
      possibility of false positive and negative results - it should be combined with
      other laboratory methods.

PMID- 16897955
TI  - [Production of interferon-gamma and interleukin-10 by splenic cells of mice
      infected with Toxoplasma gondii or immunized with antigens of killed parasites].
AB  - Splenic lymphocytes from T. gondii infected mice produced high levels of IFN
      gamma in vitro. The production of IFN-gamma was increasing until 10-th day of
      infection, reaching a level 1600-fold higher to that found in control cultures,
      then it began to decrease. The level of IL-10 released by lymphocytes to the
      medium was also increasing up to the 10-th day of infection, afterwards its
      content dropped down to the level 18-fold higher than that at the beginning of
      experiments. There were no effects of immunization with antigens of killed
      parasites on the production of IFN-gamma by splenic cells in vitro.

PMID- 16897956
TI  - [Prevalence of Toxoplasma gondii and analysis of specific immunoglobulins
      concentration in serum of women during the reproductive period in a sample of
      Wloclawek population].
AB  - The aim of the study, from 1996 to 1999, was to investigate the serological
      course of prevalence Toxoplasma gondii in 985 women of procreation period. In non
      - pregnant women the incidence of Toxoplasma gondii specific IgG was
      significantly higher (59.0 +/- 1.9%) than in pregnant women (43.4 +/- 2.8%).
      Specific IgM was less frequent (from 1.47 +/- 1.02% to 1.76 +/- 0.66%).

PMID- 16897957
TI  - [Anti - T. gondii antibody concentration in sera of pregnant women in the sample
      of Lodz population].
AB  - The aims of the study were: to estimate the prevalence of Toxoplasma gondii in
      pregnant women in the Lodz region; to assess the rate of incidence of suspected
      recent infection based on the results of the standard test for specific anty -T.
      gondii IgG and IgM antibodies. The study covered 1920 pregnant women served in
      1998 by Toxoplasma Reference Laboratory in Lodz. T. gondii specific IgG and IgM
      were quantitated by an enzym-linked immunoabsorbent assay (ELISA, Organon). We
      have demonstrated high prevalence of T. gondii among pregnant women in the Lodz
      region. In the analysed sample of Polish population the T. gondii-specific IgG
      with negative IgM occurred in 43.4% (n = 837). In 1.42% of pregnant women IgG and
      IgM specific antibodies were detected.

PMID- 16897958
TI  - [Prenatal diagnostics of Toxoplasma gondii invasion by quantitative method of PCR
      TaqMann].
AB  - Routine serological diagnosis of toxoplasmosis provides high sensitivity, but not
      high specificity. The high sensivity combined with high specifity offered by PCR
      TaqMann as well as the degree of infection led us to investigate the presence and
      levels of T. gondii DNA in amniotic fluid, maternal and neonatal blood in cases
      of pregnancy where infection with this agent was suspected. Samples of amniotic
      fluid and blood were taken from pregnant women. Postnatal blood samples were also
      taken from their infants. Presence and levels of toxoplasma DNA was investigated
      using PCR-TaqMann. PCR products were detected by electrophoresis on
      polyacrylamide gel. The PCR-TaqMann test is highly sensitive, specific and useful
      method allowing detection of the parasite genome and assessement of its level.

PMID- 16897959
TI  - [Detection of Toxoplasma gondii DNA by PCR in mother's blood, amniotic fluid and
      child's blood in selected cases of pathological pregnancy].
AB  - Prenatal screening of Toxoplasma gondii infection is controversial. The diagnosis
      is based on serological tests detecting IgM and IgG antibodies against T. gondii,
      but interpretation of these tests results is often confusing. It is commonly made
      retrospectively when serological screening indicates a possibility of recent
      infection. Most women have antibodies against T. gondii and serial testing is
      required only in monitoring of pregnancies where initial screening is negative.
      The introduction of Polymerase Chain Reaction (PCR) assay for detection of
      Toxoplasma gondii DNA in selected cases of pathologic pregnancies has permitted a
      more accurate and faster diagnosis of congenital toxoplasmosis infections.

PMID- 16897960
TI  - [Evaluation of the postnatal treatment efficacy in congenital toxoplasmosis
      identified by the newborn screening programme].
AB  - The effectiveness of neonatal screening for anti-Toxoplasma IgM or IgA and IgM
      specific antibodies followed by an intensive anti-parasitic therapy for a
      prevention of clinical and immunological reactivations of congenital infection
      was studied. Thirty-five congenitally infected infants were included into
      clinical and serological follow-up. The children were mostly asymptomatic at
      birth or they expressed some non-specific reversible clinical abnormalities in
      neonatal period. Clinically overt toxoplasmosis occurred in 10 patients,
      including one infant with a severe form; 2 children had co-existing CMV
      infections. During the follow-up period, no clinical relapses were reported.
      Asymptomatic immunological rebounds of IgG or of IgG and IgA specific antibodies
      were observed in 16 patients. Anti-parasitic treatment initiated soon after birth
      seems to be promising in a prevention of early clinical sequelae of congenital T.
      gondii infection.

PMID- 16897961
TI  - [Algorithm of diagnostic procedure in candidosis of male genital organs].
AB  - The results of earlier own studies performed in male patients with symptomatic
      candidosis of genital organs enabled to work out an algorithm of diagnostic
      procedure to determine of the fungal reservoir in a male patient. The study
      comprised 50 persons: 25 males and 25 female partners with clinical signs of
      recurrent genital organs candidosis. To mycological examination 6 specimens from
      males and 5 from females were collected. A total number of 275 cultures was
      examined. In the 45% of patients fungi were detected in all foci of infection. In
      the some cases (20%) fungal strains were isolated in males only from ejaculate
      but from their sexual partners from all examined specimens. Clinical and
      mycological cure often required more than one administration of oral antifungal
      agents.

PMID- 16897963
TI  - [Proteolytic activity of Candida albicans strains isolated from women's genital
      organs with clinical diagnosis of mycosis].
AB  - The aim of the presented study was to assess the in vitro activity of aspartate
      proteinase of strains isolated from women's genital organs with clinical
      diagnosis of mycosis. We have evaluated the activity of proteinase of 75 Candida
      albicans strains using Staib method with Rozga modification, in agar medium with
      human albumin at pH 4.6. The proteolysis zone ranged from 4.0 to 11.0 mm. The
      values of proteolysis zones in human albumin of C. albicans were similar to left
      oblique normal distribution. High and extremely high proteolytic activity is
      characteristic for more than 50% of strains.

PMID- 16897962
TI  - [Multifocal fungal infections in pregnant women].
AB  - The aim of the study was to estimate the prevalence of fungi in monofocal and
      multifocal infections in pregnant women. 251 pregnant women were examined for
      presence of fungi in vagina, oral cavity and rectum. Fungal strains were
      recovered in 259 out of 753 samples (49.2% of all pregnant women). Presence of
      fungi in vagina was associated with the invasion of oral cavity and/or rectum in
      98% of all women. Monofocal vulvovaginal mycosis was found only in 1.9% of the
      cases. Bifocal infections depended on the ontocenoses: vagina - oral cavity
      (32.1%); vagina--rectum (7.5%); oral cavity--rectum (13.2%). Trifocal infections
      (vagina - oral cavity--rectum) occurred in 58.5% of all examined women.

PMID- 16897964
TI  - [Susceptibility to itraconazole and miconazole of fungi strains isolated from the
      vaginal ontocenosis].
AB  - The activity of itraconazole (RO 51211, molecular weight 705,64) and miconazole
      (RO 14889, molecular weight 479,15) obtained from Janssen Pharmaceutica NV,
      against 100 fungi strains, was studied. These strains were isolated from vaginal
      materials of patients with recognized candidosis. The axenic fungal strains were
      assessed by own methods and unified tests (bioMerieux: API 20 C, API 20 C AUX).
      The minimal inhibitory concentration (MIC) values calculated from dose-response
      curves on agar diffusion-test (Kadlubowski's method), were also examined by
      analysing the variation (mean x +/- standard error, median Me, mode Mo, Min-Max).
      The drug MIC values for all strains were characterized by a wide range of
      variation itraconazole 0.0001 - 5.30 mg/L, miconazole 0.0045 - 4.70 mg/L; the
      shape of MIC values variation polygons was similar to normal distribution.

PMID- 16897966
TI  - Search for the pathogenic fungi in amniotic fluid.
AB  - Intra-amniotic infection with Candida is rare but considers an etiological factor
      for preterm rupture of membranes (PROM). The aim of the study was the
      investigation of the mycotic invasion of the amniotic cavity in pregnant women
      with PROM and with intact fetal memranes. 170 women were included in two groups:
      I (n = 150)--women with intact membranes; II (n = 20)--women with PROM. Samples
      of amniotic fluid were cultured on Sabouraud's medium. Fungal strains were
      isolated also from vagina, oral cavity and rectum of women with PROM.
      Intraamniotic infections were absent both in women with PROM and with intact
      membranes. Candida strains were isolated from vagina, oral cavity, and rectum in
      the group of women with PROM. Coexisting of multifocal Candida infections in
      pregnant women with PROM indicates that in those cases mycologic diagnosics
      should be recomended.

PMID- 16897965
TI  - [Some aspects of fungi multifocal invasions connected with the genital organs in
      women].
AB  - The aim of presented study was analysis of fungal invasions of the genital
      organs, oral cavity and digestive tract in 799 women. Fungal strains were
      identified using API 20C and API 20C AUX (bioMerieux); they were as follows:
      Candida albicans, C. krusei, C. tropicalis, C. guilliermondii, C. kefyr, C.
      glabrata, C. famata, C. parapsilosis, Rhodotorula rubra, Geotrichum candidum. The
      number of fungal strains isolated from the oral cavity ontocenosis was the
      highest (41.8 +/- 2.4%). Fungal strains isolated from the vagina were less
      numerous (34.6 +/- 2.3%), and from the rectum the least numerous (23.6 +/- 2.1%).
      Multifocal invasions (limited to one ontocenosis) were present in about 50% of
      women; bifocal were less frequent, and this difference was statistically
      significant (p < 0.01): fungi in the vagina and oral cavity were detected in 28.6
      +/- 3.0%, in the oral cavity and rectum in 19.0 +/- 2.6%, and in the vagina and
      rectum in 13.0 +/- 2.2%. Trifocal invasions were more frequent (39.4 +/- 3.2%).
      There was a visible trend of increasing prevalence of fungi in genital organs
      over 10 year period from 17.9 +/- 1.4% to 34.5 +/- 1.7%.

PMID- 16897967
TI  - [Timeline from discovery of 5-FU to development of an oral anticancer agent S-1
      and its drug concept].
AB  - C. Heidelberger et al left great gifts to us. Approximately 50 years have elapsed
      since their discovery of 5-FU in 1957 before eventually elucidating the
      mechanisms by which the drug exerts its pharmacological actions and provokes its
      adverse reactions. Namely, 5-FU is a typical antimetabolite with strong time
      dependency, and continuous venous infusion(CVI) is considered to be its optimal
      regimen. The following facts may be mentioned to explain why such a long period
      of time has been spent to reach this level of research: 1) 5-FU, when
      administered to the living individual, is mostly inactivated by hepatic catabolic
      enzymes without delay and is then excreted in the urine, thus making it difficult
      to precisely analyze the relationship of blood 5-FU concentrations with
      concentration persistence, anticancer activity, and adverse reactions; and 2)
      unlike other anticancer agents, an antimetabolite 5-FU separately generates
      metabolites which show anticancer activity and adverse reactions, as well as
      metabolites which show adverse reactions only. For the last 30 years, we paid
      attention especially to 5-FU among chemotherapeutic agents for cancer and have
      sought for a long-lasting therapeutic modality which maintains quality of life of
      the patient and patient compliance by considering the balancing between its
      effects and adverse reactions. Consequently, we concretized an innovative
      therapeutic drug, TS-1 (S-1). We have a long history of research before
      developing S-1, which is represented by a series of investigations consisting in
      the developments of Futrafur (FT)--an oral anticancer agent of a 5-FU derivative
      (prodrug)-in 1970 subsequent to the above discovery of 5-FU, of UFT(FT: Ura=1 :
      4) in 1976, and of S-1 in 1999. To date, we took the initiative in the world to
      devise S-1, the first self-rescuing concept(SRC)-based anticancer agent with dual
      actions, i.e., enhancement of pharmacological actions of 5-FU and reduction of
      its adverse reactions, by making use of the biochemical and enzymological
      properties of 5-FU and by combining FT, which is gradually converted to 5-FU in
      the body, with a 5-FU's effect-enhancing substance and a 5-FU's adverse reaction
      reducing substance. S-1 is an oral anticancer agent in capsule, in which the
      following 2 modulators for 5-FU are combined to FT: one is CDHP(5-chloro-2,4
      dihydroxypyridine) which increases blood concentrations and enhances
      pharmacological actions of 5-FU by potently inhibiting the degradation of 5-FU;
      and another is Oxo(potassium oxonate) which is localized in the mucosa of the
      gastrointestinal (GI) tract after oral administration and reduces GI toxicities
      provoked by 5-FU. S-1 is an oral anticancer agent in which these 3 components,
      FT, CDHP, and Oxo, are combined at a molar ratio of 1 : 0.4 : 1. Our conception
      to develop an SRC-based therapeutic drug and the preclinical concepts validated
      by numerous basic studies were demonstrated also in the clinical trials. In
      January 1999, S-1 was approved for the treatment of advanced and recurrent
      gastric cancers through the priority review system. From 2001 to 2005, S-1 was
      approved for the treatment of head and neck cancer, colon cancer, non-small cell
      lung cancer, and breast cancer. S-1 has been applied to acquire its expanded
      indications for the treatment of pancreatic cancer and biliary tract cancer. We
      are confident that the combined regimen of S-1 with other anticancer agents and
      with other therapeutic modalities will contribute to the routine medical practice
      of cancer treatment in the future.

PMID- 16897968
TI  - [Antitumor activity and function of S-1, a new oral tegafur-based formulation].
AB  - TS-1 (S-1), developed by the scientific theory of both potentiating antitumor
      activity of 5-fluorouracil (5-FU) and reducing gastrointestinal toxicity induced
      by 5-FU, is a new oral formulation consisting of 1 M tegafur, 0.4 M gimeracil and
      1 M oteracil potassium. We investigated the antitumor efficacy of S-1 alone and
      in combination with other cytotoxic anticancer drugs using subcutaneously or
      orthotopically implanted murine and human tumors in rodents. As a single agent, S
      1 showed higher antitumor activity with its low intestinal toxicity compared to
      continuous venous infusion 5-FU, the most effective dosing method of 5-FU, and/or
      to clinically available oral fluoropyrimidines such as UFT, doxyfluridine and
      capecitabine on various murine tumors and human tumor xenografts. Especially, it
      was noteworthy that S-1 as a DPD-inhibitory fluoropyrimidine markedly affected
      human tumor xenografts with high expression levels of DPD on which other
      fluoropyrimidines showed a low antitumor activity. In combination with other
      anticancer drugs such as CPT-11 and taxanes, S-1 exercised synergistic antitumor
      efficacy not only on 5-FU-sensitive tumors with low expression levels of
      thymidylate synthase (TS) but also on 5-FU-resistant tumors with originally
      higher and/or elevated levels of TS expression. As one of the reasonable
      mechanism of antitumor synergism by the combination, CPT-11 and taxanes were
      found to reduce the expression of TS in human tumor resistant to 5-FU with high
      expression TS levels. Throughout our preclinical antitumor studies of S-1, alone
      and/or in combination with other anticancer drugs, it would be expected to
      contribute greatly to the treatment of cancer patients.

PMID- 16897969
TI  - [Pharmacokinetics of S-1].
AB  - S-1 is an attractive oral fluorouracil antitumor drug, which is being called "a
      self-rescuing drug". This novel oral fluoropyrimidine is combined with three
      pharmacological agents: tegafur (FT) which is a prodrug of 5-fluorouracil (5-FU),
      5-chloro-2,4-dihydroxypyridine (CDHP) which inhibits dihydropyrimidine
      dehydrogenase (DPD) activity, and potassium oxonate (Oxo) which reduces
      gastrointestinal toxicity. Phase I and an early phase II clinical trials were
      performed about ten years ago, and these results had already been introduced to
      the Journal "Clinical Cancer Research Vol. 5, pages 2000-2005, 1999". The data of
      this article in this journal was referred from the results of the figures and
      tables based on the above trial. Most of the authors in this article have
      contributed on that pharmacokinetics study and published the above manuscripts.
      In that study, the pharmacokinetics of 5-FU, intact FT, CDHP and Oxo after
      administration of the standard dose of S-1 had been performed. These studies were
      carried out at two hospitals, Department of Surgery (Section 1) Sapporo Medical
      University and Chemotherapy Cancer Center, Cancer Institute Hospital and Japanese
      Foundation for Cancer Research (Ohtsuka). The number of patients accepted for
      this trial is twelve, 5 patients with gastric cancer, 4 with colorectal cancer
      and 3 with breast cancer. Single administration trial was referred to all
      patients, but consecutive administration trial was limited to ten patients. The
      results of plasma concentration, Cmax, Tmax, AUC0-14, and T1/2 of 5-FU, FT, CDHP,
      and Oxo were ascertained in details. It was a surprise that the indicated data
      was very similar to that of the intravenous 5-FU continuous infusion. Therefore,
      the low dose administration of 5-FU (FT) as S-1 may result in good antitumor
      effects with minimum adverse effects to the patients.

PMID- 16897970
TI  - [Plasma concentrations of 5-fluorouracil and F-beta-alanine following oral
      administration of S-1, a dihydropyrimidine dehydrogenase inhibitory
      fluoropyrimidine, as compared with protracted venous infusion of 5-fluorouracil].
AB  - The pharmacokinetics and pharmacodynamics of oral S-1, a dihydropyrimidine
      dehydrogenase (DPD) inhibitory fluoropyrimidine, were compared with those of
      protracted venous infusion (PVI) of 5-fluorouracil (5-FU). In all, 10 patients
      with gastric cancer received PVI of 5-FU at a dose of 250 mg/m2/day for 5 days.
      After a washout period of 9 days, the 10 patients received two divided doses
      daily for 28 days. S-1 was administered orally at about 9 a.m. and 7 p.m. Plasma
      concentrations of 5-FU and F-beta-alanine (FBAL) were measured for
      pharmacokinetic analysis, and the plasma uracil concentration was monitored as a
      surrogate marker of DPD inhibition in the same 10 patients on days 1-5 of PVI of
      5-FU and on days 1-5 of oral S-1. The area under the curve (AUC0-10h) of 5-FU on
      day 5 was 728 +/- 113 ng x hr/ml for PVI of 5-FU and 1,364 +/- 374 ng x hr/ml for
      S-1. The median 5-FU PVI: S-1 ratio of the AUC0-10h of 5-FU was 1.9. The AUC0-10h
      of FBAL on day 5 of PVI of 5-FU was 9,465 +/- 3,225 ng x hr/ml, AUC0-10h, as
      compared with 1,725 +/- 605 ng x hr/ml on day 5 of S-1 treatment. The AUC0-10h of
      uracil on day 5 was 252 +/- 60 ng x hr/ml with PVI of 5-FU and 12,582 +/- 3,060
      ng x hr/ml with S-1. The AUC0-10h of FBAL was markedly lower and plasma uracil
      concentrations were significantly higher for S-1 than for PVI of 5-FU, clearly
      demonstrating the effect of DPD inhibition.

PMID- 16897971
TI  - [S-1 for gastric cancer-S-1 monotherapy and its progress].
AB  - Two pivotal phase II studies of S-1 in advanced gastric cancer showed response
      rates of 44% and 49%, and the overall survival time was 207 and 250 days,
      respectively. The response rate of S-1 exceeded the response rates of other
      approved drugs, and was comparable to that of combination chemotherapies such as
      5-fluorouracil (5-FU) plus cisplatin (CDDP). These data suggested that S-1 could
      be used as a first-line drug for gastric cancer with a great advantage in quality
      of life (QOL), because it is an oral drug and can be used at an outpatient
      clinic. The overall incidences of adverse reactions in the phase II studies were
      74.3%, and that of grade 3 or worse were 14.9%. The main adverse reactions were
      myelosuppression and GI toxicities. As hematological toxicity was more common
      than other oral fluoropyrimidine derivatives such as UFT, a careful hematological
      monitoring is necessary. To confirm the survival benefit of S-1 in advanced
      gastric cancer, a phase III trial of S-1 vs 5-FU vs CDDP plus irinotecan (CPT-11)
      has been conducted by the Japan Clinical Oncology Group (JCOG), and these results
      have been awaited. Furthermore, the combination of S-1 with CDDP, CPT-11 or
      taxane for the treatment of gastric cancer is feasible and active, and phase III
      studies of S-1 vs several combination therapies including S-1 are also in
      progress. The effect of S-1 in adjuvant setting is also promising. Currently, a
      phase III study of surgery alone vs S-1 in patients with a curative resection of
      gastric cancer has been developed. Further therapeutic benefits are also expected
      by combining S-1 with other chemotherapeutic agents such as molecular targeted
      agents.

PMID- 16897972
TI  - [Japanese nationwide post-marketing survey of S-1 in patients with advanced
      gastric cancer].
AB  - BACKGROUND: The aim of this survey was to confirm the safety and efficacy of S-1
      for advanced gastric cancer after market release. PATIENTS AND METHODS: All
      patients had to be registered with the manufacturer for a post-marketing survey,
      according to the government recommendation. All patients were monitored for
      safety and survival. RESULTS: During this survey, a total of 4,177 patients with
      advanced gastric cancer were registered. The incidences of all adverse events and
      of grade 3 or worse events in the 3,808 patients evaluable for safety were 74%
      and 25%, respectively. In patients with lower creatinine clearance at baseline,
      the incidences of adverse reactions were higher for all grades combined, as well
      as for grade 3 or worse. There were 90 (2.4%) early deaths (within 30 days of the
      initiation of the treatment) and 5 (0.1%) deaths possibly related to the
      treatment. The median survival time and the 1-year survival rate for all patients
      evaluable for efficacy (n=3,801) were 8.3 months (95% CI: 8.0-8.6 months) and
      33.3% (95% CI: 31.8-34.9%), respectively. CONCLUSION: This nationwide survey
      confirmed that the safety and efficacy profiles of S-1 were similar to those seen
      in the registration study.

PMID- 16897973
TI  - [Clinical development of S-1 (TS-1) for advanced gastric cancer].
AB  - The 5-FU plus cisplatin containing regimen like FP, ECF and DCF, is considered to
      be the most effective treatment for advanced gastric cancer in the United States,
      Europe, and Korea. In Japan, oral fluoropyrimidine S-1 (TS-1) is currently
      considered to be the first candidate as the standard drug for advanced gastric
      cancer. S-1 based combination therapies with other promising drugs like
      cisplatin, irinotecan and taxanes, are expected to yield good results. Above all,
      S-1+CDDP therapy showed a high efficacy and expected to be a standard therapy for
      advanced gastric cancer. Two large phase III studies, JCOG 9912 5-FU vs S-1 vs
      CPT-11 +CDDP and S-1 vs S-1+CDDP, are now on going to establish an acceptable
      frontline standard for patients with AGC. We therefore need to develop new agents
      and combination chemotherapy regimens to achieve a greater survival benefit in
      AGC.

PMID- 16897974
TI  - [S-1 combined with weekly dosing of cisplatin for metastatic gastric cancer].
AB  - We developed a combination chemotherapy, comprising weekly dosing of iv cisplatin
      (days 1 and 8) combined with a fixed dose (70 mg/m2/day) of S-1 (days 1-14) for
      patients with metastatic gastric cancer. The treatment was repeated every 3
      weeks. Twenty patients were studied. Dose-limiting toxicities of grade 3 diarrhea
      and stomatitis were observed in one patient at the dose of cisplatin 20 mg/m2.
      Grade 2 gastrointestinal adverse reactions, such as nausea and anorexia, were
      seen in approximately half of patients at this dose level within the first two
      treatment cycles. This was the maximum acceptable level. The overall response
      rate in 18 patients evaluated was 61%. The median survival was 11 months, despite
      including 11 pre-treated patients. S-1 given with weekly cisplatin was a feasible
      and promising combination regimen for an outpatient setting.

PMID- 16897975
TI  - [S-1+Low-Dose CDDP].
AB  - A review of the published literature was undertaken to ascertain the trends in
      treatment schedules of combination of an oral fluorouracil derivative S-1 with
      low-dose CDDP (25 mg/m2 or less) for un-resectable and recurrent gastric cancer.
      The case reports demonstrated as follows: S-1 was given as standard doses of 80
      120 mg/body. With regard to CDDP administration, 4 mg/m2 or less was given for 4
      consecutive weeks following 2-weeks rest and 6-10 mg/m2 was given for 3
      consecutive weeks following 2-weeks rest in the case of 5-day/week CDDP
      administration. There have been reports of 6-8 mg/m2 CDDP given once or twice a
      week and weekly CDDP of 10-25 mg/m2 without grade 3 or more adverse events. A
      phase I study demonstrated the recommend dose of CDDP in the case of 5-day/week
      was 4 mg/m2 in the regimen of 4-consecutive weeks and 2-weeks rest with a
      standard dose of S-1. Three phase I studies on weekly low-dose CDDP with S-1
      showed the recommend doses were 20-25 mg/m2. S-1+low-dose and a high-dose (30-90
      mg/m2) CDDP have come into wide use in Japan. There have been no differences
      between the case reports and the clinical studies in quantity and quality for
      both regimens. The unified regimen of S-1+low-dose CDDP as an outpatient based
      chemotherapy should be developed.

PMID- 16897976
TI  - [Irinotecan plus oral S-1 in patients with advanced gastric cancer-biweekly IRIS
      regimen].
AB  - We reported the results of phase I study with CPT-11 and S-1 (IRIS) in advanced
      gastric cancer (AGC) patients at ASCO 2002. Now I present an outline of this
      phase I/II trial. A combined treatment of IRIS (CPT-11 + S-1) was given to the
      AGC patients who had not received prior chemotherapy. S-1 was orally administered
      twice a day for 14 days, and CPT-11 was administered as a 90-minute intravenous
      infusion on days 1 and 15. This schedule was repeated every 4 weeks. Fifteen
      patients were registered in this phase I study and 9 patients were added in this
      phase II study. Non-hematological toxicities were almost classified as grade 2 or
      lower, except for grade 3 nausea and grade 3 dermatitis of level 2. These adverse
      events were manageable by administering anti-emetic drugs and a drug rest. As for
      hematological toxicities, grade 4 neutropenia occurred with one patient at level
      1 and level 2 in phase I. And grade 4 neutropenia occurred with four patients at
      level 2 in phase II. However, they recovered after the drug rest, and we could
      continue the administration based on the standard dose modifications. These side
      effects were tolerable, and the overall response rate was 54.2%. MST of this
      regimen is 581 days. The IRIS treatment is effective and tolerable for outpatient
      treatments.

PMID- 16897977
TI  - [Combination chemotherapy of S-1 +CPT-11 (q 4-5 w) for metastatic gastric
      cancer].
AB  - The effectiveness of systemic chemotherapy for metastatic gastric cancer has
      already been established. However, a standard chemotherapy still remains
      uncertain. New agents such as S-1, CPT-11 and taxanes are markedly improving the
      response rates for gastric cancer. Including these new drugs, several randomized
      phase III trials are ongoing in Japan. In the near future, the candidate for
      standard regimen to treat gastric cancer will be reported. In this article, we
      described the current state of S-1 +CPT-11 combination chemotherapy for gastric
      cancer. Among various CPT-11 based chemotherapy, S-1 +CPT-11 appears to be the
      most effective and less toxic treatment.

PMID- 16897978
TI  - [Combination chemotherapy of S-1 and docetaxel on advanced and recurrent gastric
      cancer].
AB  - In the present article, we have summarized the phase I/II clinical trials on
      combination therapy of S-1 and docetaxel. With result of the phase I study,
      patients were treated with intravenous infusion of 40 mg/m2 docetaxel on day 1
      and oral S-1 80 mg/m2/day on days 1 to 14 every 3 weeks. Forty eight patients
      received a total of 272 treatment cycles. No complete responses (CRs) and 27
      partial responses (PRs) were observed for an overall response rate (CR+PR) of
      56.2% (95% CI, 38-66%). Eighteen patients (37.5%) had stable disease (SD), and 3
      patients (6.2%) had progressive disease (PD) as best response. The tumor control
      rate (CR+PR+SD) was 93.8% (95% CI, 83-98%). The median overall survival was 14.3
      months (95% CI: 10.7-20.3 months) and the median time to tumor progression was
      7.3 months (95% CI: 4.2-10.7 months). The most common grade 3-4 hematologic
      toxicities were neutropenia 58.3%, leukopenia 41.7%, febrile neutropenia 8.3%,
      and anemia 8.3%. The most common grade 3 nonhematologic toxicities were anorexia
      14.6%, stomatitis 8.3%, nausea 6.3%, diarrhea 4.2%, constipation 4.2%, and
      vomiting 2.1%. No grade 4 nonhematologic toxicities were reported, and all
      treatment-related toxicities were resolved. The mechanisms underlying these
      synergistic effects of S-1 and docetaxel were examined by expression and activity
      analyses of 5-FU metabolic enzymes. The expressions of thymidylate synthase (TS)
      and dihydropyrimidine dehydrogenase (DPD) were decreased and that of orotate
      phosphorybosyl transferase (OPRT) was increased in mRNA, protein level and
      activity assay after the treatment with docetaxel and 5-FU in the TMK-1 gastric
      cancer cell. These findings strongly indicate that the combination chemotherapy
      of docetaxel and S-1 is effective against gastric carcinomas and therefore is a
      good candidate as a standard chemotherapeutic strategy in treating these tumors.

PMID- 16897979
TI  - [Combination chemotherapy of S-1 plus biweekly docetaxel for advanced and
      recurrent gastric cancer].
AB  - The S-1 +biweekly docetaxel (DOC) combination therapy was evaluated for advanced
      or recurrent gastric cancer patients. This combination therapy was evaluated in
      vitro using the nude rat-gastric cancer xenograft system. S-1 alone or DOC alone
      showed antitumor activity, and the antitumor activity was synergistic when two
      drugs were combined. In clinical settings, the schedule was S-1 80 mg/m2 (day 1
      14, orally) and DOC (day 1 and day 15, intravenously) followed by a 2-week rest.
      In phase I study, the dose of DOC was evaluated, and a recommended dose for phase
      II was determined as 35 mg/m2. The entry for phase II study was completed, and
      the preliminary results of 33 patients showed the response rate of 21.2%. The
      incidence of more than grade 3 adverse effects was 29%(neutropenia,
      leukocytopenia, anorexia and mucositis). The S-1 +biweekly DOC combination
      therapy can be a candidate for outpatient chemotherapy for advanced or recurrent
      gastric cancer.

PMID- 16897980
TI  - [S-1 combined with weekly paclitaxel in patients with advanced gastric cancer].
AB  - S-1 Combined with Weekly Paclitaxel in Patients with Advanced Gastric Cancer:
      Masahiro Gotoh, Shin-ichiro Kawabe and Hiroya Takiuchi (Dept. of
      Gastroenterology, Osaka Medical College) Summary Both paclitaxel and S-1 have
      been identified as an effective agent for the treatment of gastric cancer.
      Furthermore, weekly paclitaxel was found to have a better toxicity profile and to
      be as effective as an equivalently dosed conventional schedule of delivery every
      3 weeks. Osaka Gastrointestinal Cancer Chemotherapy Study Group (OGSG) conducted
      the phase I/II study of weekly paclitaxel combined with S-1. S-1 was given orally
      at a fixed dosage of 40 mg/m2 bid for 14 consecutive days, followed by a week
      rest. Paclitaxel was scheduled to be given intravenously on days 1 and 8. The MTD
      of paclitaxel was presumed to be 60 mg/m2 because 50.0% of patients (2/4)
      developed DLTs (mainly grade 3 anorexia). Therefore, the RD of paclitaxel was
      estimated to be 50 mg/m2. This combination treatment was demonstrated to exhibit
      a tolerable toxicity profile with a high antitumor activity of 48% (14/29) and
      MST of 417 days. This regimen is investigated in a randomized phase II trial and
      may yet become a test arm in future phase III trials.

PMID- 16897981
TI  - [Combination chemotherapy study of biweekly paclitaxel and S-1 administration in
      patients with advanced gastric cancer].
AB  - In the present article, we report the results of phase I/II combination
      chemotherapy study of biweekly paclitaxel and S-1 administration in patients with
      advanced gastric cancer. In the phase I study, we could determine the recommended
      dose for the phase II study with paclitaxel and S-1 to be 120 mg/m2 and 80 mg/m2,
      respectively. The side effect was not so severe. The overall response was 53%. In
      conclusion, biweekly paclitaxel and S-1 administration can be safely combined for
      the treatment of advanced gastric cancer. This combined therapy represents a
      novel and active treatment regimen with low toxicity and can be defined as safe
      and effective. Now we are analyzing the result of the phase II study.

PMID- 16897982
TI  - [A recent trial of chemo-radiation with S-1 against gastric cancer].
AB  - A recent development of novel anticancer agents like S-1, CPT-11 or taxanes has
      improved a therapeutic outcome for advanced gastric cancer, while conventional
      anticancer agents showed less anticancer effect against gastric cancer. The
      present main drug in Japan is S-1, which is easily used for outpatient with a
      high efficacy rate and low toxicity, also shows better effect in combination with
      other anticancer drugs than S-1 alone. In the present article, we demonstrated
      significant meaning of additional radiation therapy with anticancer drugs like S
      1. With novel anticancer drugs like S-1, we will expose a clinical advantage and
      appropriateness for chemo-radiation therapy against gastric cancer discussed in
      the present references according to chemo-radiation therapy. Although chemo
      radiation therapy has been recognized as one of the standard therapies for
      gastric cancer in Western countries, radiation therapy was selected in Japan for
      palliation therapy of recurrent disease or a terminal cancer to improve patients'
      QOL. On the other hand, we demonstrated in our trial of chemo-radiation therapy
      with S-1/low-dose CDDP/radiation (TSLDR), which was applied to initial treatment
      against highly advanced Stage IV gastric cancer and revealed the usefulness of
      the regimen in anticancer effect and toxicity. In addition, chemo-radiation
      therapy including novel anticancer agents like S-1 will be discussed based on
      various kinds of view points, expecting a better clinical outcome of multimodal
      therapies against advanced gastric cancer.

PMID- 16897983
TI  - [S-1 combined with lentinan in patients with unresectable or recurrent gastric
      cancer].
AB  - Lentinan (LNT) is a beta-glucan known to have a life-prolonging effect in
      combination with chemotherapy for patients with unresectable or recurrent gastric
      cancer. Thus, a multi-center trial of chemo-immunotherapy using S-1 combined with
      LNT may benefit patients with unresectable or recurrent gastric cancer with
      acceptable toxicity. With such a regimen, the median survival time in 32 patients
      was 559 days. Regardless of change to second-line chemotherapy, the mean period
      of using S-1+LNT for patients with long NC above 400 days was 725 days. In subset
      analyses, the survival period of the patients with G/L ratio of equal to or less
      than 2 was significantly better than that of the higher one (p<0.0001). The
      incidence of hematological toxicity (grade 3 leukopenia and thrombocytopenia) was
      6.3% (2/32), and non-hematological toxicity (grade 2 dysgeusia) was 6.3% (2/32),
      while no grade 4 toxicity was observed. S-1 and LNT combination immunotherapy was
      carried out safely with high QOL and allowed a prolonged administration. S-1+LNT
      regimen may prolong NC periods in patients with unresectable or recurrent gastric
      cancer.

PMID- 16897984
TI  - [Adjuvant chemotherapy using S-1 for curatively resected gastric cancer-the
      nationwide clinical trial].
AB  - Actually there has been no established adjuvant therapy for curable gastric
      cancer. Thus it is strongly recommended in the guidelines to actively carry out
      clinical trials. A large scale clinical trial on adjuvant chemotherapy for
      gastric cancer using S-1 (ACTS-GC) started in 2001. This was the first large
      trial having the surgery alone as control after 1980. The target population was
      Stage II, IIIA, IIIB, and the expected hazard ratio was less than 0.70. Between
      October 2001 and December 2004, for 3 years and 2 months, 1,056 patients were
      enrolled. Thus it was proven that we should carry out a pivotal study instead of
      making meta-analysis in the field of gastric cancer. Certainly, the results of
      this trial will strongly affect the clinical practice in Japan. If the results
      are negative, the use of adjuvant chemotherapy in practice and in social
      insurance might be restricted.

PMID- 16897985
TI  - Rapid development of S-1 in the west for therapy of advanced gastric carcinoma.
AB  - Therapy for patients with advanced gastric cancer is not satisfactory. The median
      survival of patients with advanced gastric cancer is approximately 6-9 months and
      less than 10% of patients survive one year. Despite identification of new classes
      of agents, such as camptothecins, taxanes, and new platinum analogs, the
      improvement has been limited and therapy intensive resulting in considerable
      morbidity. More intensive therapies are challenging not only for the patients and
      their relatives but also for the health care providers. Oral fluropyrimidines
      like capecitabine and S-1 have generated considerable interest because of
      convenience and their activity against gastric carcinoma. S-1 is of significant
      interest because of many studies in Japan in gastric cancer patients
      demonstrating its substantial activity as a single agent and in combination with
      other agents. Furthermore, S-1 represents a fourth generation "designer" drug. It
      has a component that enhances the cytotoxic activity of tegafur by inhibiting
      dihydropyrimidine dehydrogenase (DPD) and also has a component that reduces
      phosphorylation of 5-fluorouracil in the gastrointestinal tract to potentially
      reduce toxicity. This unique combination is rarely found in an oral agent. In
      addition, considerable ethnic differences in the tolerated doses of S-1 have been
      considered related to varying efficiency rates of conversion of tegafur to 5
      fluorouracil by the CYP450 enzyme system. The varying efficiency is thought to be
      due to the presence of certain polymorphisms in the CYP2A6 gene responsible for
      metabolizing tegafur to 5-fluorouracil. S-1 is under rapid development in the
      West for gastric carcinoma. Phase I/II studies of the combination of S-1 plus
      cisplatin have been completed and a global phase III study, accruing rapidly, is
      comparing S-1 plus cisplatin to 5-fluorouracil plus cisplatin (a reference
      regimen).

PMID- 16897986
TI  - [S-1 as a single agent for colorectal cancer].
AB  - Chemotherapy for colorectal cancer is now improving rapidly due to new drugs like
      oxaliplatin and molecular targeting drugs. The key drug, however, is still 5
      fluorouracil (5-FU). S-1 is an oral 5-FU anti-tumor drug that combines three
      pharmacological agents: tegafur, 5-chloro-2,4-dihydroxypyridine, which inhibits
      dihydropyrimidine dehydrogenase activity, and potassium oxonate, which reduces
      gastrointestinal toxicity. The results of the phase II study suggested that S-1
      as a single agent was active against metastatic colorectal cancer: CR rate was 36
      40% and MST was about one-year. Toxicity was all tolerable. Clinical trials of S
      1 with oxaliplatin or CPT-11 combination chemotherapy are ongoing in Japan. S-1
      with molecular targeting drugs will also be studied. Therefore, S-1 is expected
      to play an important part in chemotherapy for colorectal cancer.

PMID- 16897987
TI  - [The current evidence of S-1 and irinotecan hydrochloride combination
      chemotherapy with tri-weekly schedule].
AB  - A combination therapy of irinotecan hydrochloride (CPT-11) with continuous
      intravenous infusions of (infusional) 5-fluorouracil (5-FU) and Leucovorin (LV)
      is often used to treat advanced colorectal cancer. However, recent concerns on
      safety and convenience have prompted the development of new oral fluoropyrimidine
      derivatives which improved regimens. Yamada et al conducted a phase I study to
      assess the maximum tolerated dose and recommended dose of S-1 combined with CPT
      11. The study recommended that 150 mg/m2 of CPT-11 be given on day 1 and 80 mg/m2
      of S-1 daily on days 1 to 14 every 3 weeks. Recently, several phase I/II studies
      assessed the efficacy and safety of the combined therapy with S-1 and CPT-11 in
      patients with advanced colorectal cancer. Some of the studies which were ongoing
      assessed a tri-weekly schedule regimen. Our results showed that S-1 plus CPT-11
      was very effective, with a response rate of 63% and PFS of 8 months. Toxicity was
      generally mild and manageable on an outpatient basis. The current evidence showed
      that a combination of S-1 and CPT-11 was more convenient and easier to administer
      than a combination of CPT-11 plus infusional 5-FU and LV. It will be essential to
      prove that the combination of S-1 plus CPT-11 can replace the combination of
      infusional 5-FU and LV plus CPT-11 without negatively affecting efficacy and
      toxicity.

PMID- 16897988
TI  - [Irinotecan plus oral S-1 in patients with advanced colorectal cancer--biweekly
      IRIS regimen].
AB  - We planned to conduct a phase II clinical study of combination therapy with CPT
      11 and S-1. The antitumor effect was the primary endpoint, while the safety,
      progression-free survival time, and median survival time were the secondary
      endpoints. The subjects were untreated patients with inoperable advanced
      colorectal cancer aged 20-75 years. Based on the results of our previous phase
      I/II study in patients with gastric cancer, the dosage was established in
      consideration of safety for outpatient therapy. CPT-11 was administered at a dose
      of 100 mg/m2 (on days 1 and 15) as an intravenous infusion over 90 minutes, and
      oral S-1 (40 mg/m2) was administered after breakfast and dinner and then
      withdrawn for 2 weeks. No other serious adverse reactions occurred (either
      hematological or non-hematological), and all patients could receive therapy
      safely on an outpatient basis. Interim analysis suggested excellent results, with
      a response rate of 50%. Combination therapy with CPT-11 and S-1 achieved a high
      response rate and could be given safely. These findings suggest that the therapy
      has potential as first-line treatment for inoperable advanced recurrent
      colorectal cancer.

PMID- 16897989
TI  - [Combination chemotherapy with S-1 plus CPT-11 for patients with advanced or
      recurrent colorectal cancer].
AB  - Various kinds of combination chemotherapies with 5-FU as a base agent have been
      performed for patients with advanced or recurrent colorectal cancer. S-1 was a
      newly developed 5-FU derivative and was orally administered. One of the
      combination therapies with S-1 plus irinotecan (CPT-11) has also been expected to
      have a better therapeutic value. Recently this combination therapy has been
      undertaken by our department, and its clinical use and toxicities are described
      in this article.

PMID- 16897990
TI  - [A randomized controlled trial to evaluate the effect of adjuvant oral
      fluoropyrimidine derivative therapy after curative resection for stage II/III
      rectal cancer-adjuvant chemotherapy trial of S-1 for rectal cancer (ACTS-RC):].
AB  - We are conducting a prospective randomized trial to evaluate the survival benefit
      of adjuvant chemotherapy with S-1 (tegafur, gimeracil, oteracil potassium) and
      UFT (uracil-tegafur) after curative surgery for patients with Stage II and III
      rectal cancer. Patients are randomized to either administration of UFT (control)
      or S-1. UFT was orally administered for 5 days (400 mg/m2/day) followed by two
      days rest for a year. S-1 was orally administered for 4 weeks (80 mg/m2/day)
      followed by two weeks rest for a year. The primary endpoint is relapse-free
      survival (RFS) rate, and the secondary endpoints are overall survival time (OS)
      and frequency or level of adverse events. We aim to include 400 patients in each
      of the treatment groups and assume that the registration period will last until
      2009.

PMID- 16897991
TI  - [Clinical efficacy of administration with S-1 alone for head and neck carcinoma].
AB  - Most head and neck carcinomas are squamous cell carcinomas (HNSCCs). The
      combination of cisplatin with a continuous infusion of 5-fluorouracil (5-FU) has
      been a standard chemotherapy regimen for HNSCC. Based on basic and clinical
      studies, the critical plasma concentration of 5-FU is suspected to be about 0.1
      microg/ml. The administration of the conventional dose of S-1 including
      dihydropyrimidine dehydrogenase (DPD), an metabolic inhibitor of 5-FU, results in
      exceeding the critical plasma concentration of 5-FU, and the long-term
      administration with high plasma concentration of 5-FU is considered to show
      clinical effectiveness in head and neck cancer. The results of early and late
      phase II studies on head and neck carcinoma were also described in the present
      paper.

PMID- 16897992
TI  - [Combination therapy with S-1 and CDDP for head and neck cancer].
AB  - The combination with cisplatin (CDDP) and 5-FU is considered the first choice
      chemotherapy for squamous cell carcinoma of the head and neck (HNSCC). S-1, a
      modulation of tegafur developed in Japan, is an active agent for HNSCC. Some
      clinical phase I/II studies about the combination with CDDP and S-1 have been
      reported. The combination showed a good response rate of 67.6% for advanced and
      recurrent HNSCC in our clinical phase I/II study. The regimens of S-1 combined
      with carboplatin or nedaplatin have also been reported. Regimens containing S-1
      appear to have been effective for HNSCC. Multi-institutional phase II studies
      with a large sample size are needed in the future. The compliance for patients is
      better than a 5-FU injection because S-1 is orally administrated. The adverse
      effect, especially for bone mallow toxicity, is equal or upgraded compared with a
      5-FU injection. The efficacy and adverse effects of CDDP plus S-1 should be
      studied in carefully designed phase II/III trials. S-1 will be one of the key
      drugs for HNSCC in the future.

PMID- 16897993
TI  - [Combination chemotherapy with S-1 and carboplatin for head and neck cancers].
AB  - Chemotherapy plays an important role in the treatment of head and neck cancer
      (HNC) patients with recurrent and/or metastatic unresectable disease. The
      standard regimen for HNC has been a combination of cisplatin (CDDP) and 5
      fluorouracil (5-FU). We planned to develop a new outpatient regimen that could be
      carried out safely and had an antitumor activity equivalent to the regimen of
      CDDP plus 5-FU. For this purpose, we selected a combination of S-1 and
      carboplatin. The overall response rate of 40.9% in this study was almost
      equivalent to the study previously reported on 5-FU plus CDDP. This regimen of S
      1 plus carboplatin has the possibility of yielding tumor responses equivalent to
      a conventional regimen of 5-FU combined with CDDP in patients with recurrent
      and/or metastatic head and neck carcinoma as a second-line palliative
      chemotherapy.

PMID- 16897994
TI  - [A combination study of S-1 and docetaxel in patients with head and neck cancer].
AB  - We determined the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), and
      efficacy of drug sequence on toxicities of the combination of S-1 and docetaxel
      for head and neck cancers. S-1 was administered at the full dose of 80 mg/m2 for
      two weeks and docetaxel on day 1 according to the following dose escalation
      schedule: level 1: 40 mg/m2, level 2: 50 mg/m2, and level 3: 60 mg/m2. DLT was
      observed in two cases of level 3. Although grade 3 leukopenia was observed in
      level 3, all of the toxicities were not severe. Recommended doses for the next
      phase evaluation were determined to be 80 mg/m2 of S-1 and 50 mg/m2 of docetaxel.
      Oral S-1 combination with docetaxel is a feasible and promising combination
      regimen that is appropriate for an outpatient setting.

PMID- 16897995
TI  - [Clinical phase I trial of concurrent chemo-radiotherapy with S-1 for T2NO
      glottic carcinoma].
AB  - We conducted a phase I study to determine a recommended dose (RD) of S-1 for
      chemo-radiotherapy consisting of S-1+ radiotherapy for T 2 N 0 larynx cancer. The
      method of administration used to assess the RD was irradiation with 2 Gy/day for
      5 days a week until a total dose of 60 Gy, and concomitant administration of S-1
      once a day for 2 weeks beginning on the day therapy was started followed by 2
      weeks off the drug and 2 weeks on the drug with the dose escalating from S-1 60
      mg/body/day (level 1) to 80 mg/body/day (level 2), and then to 100 mg/body/day
      (level 3). 18 patients were enrolled. 4 patients developed an adverse event of
      grade 3 radiation dermatitis which became a dose-limiting toxicity (DLT) at level
      3. We then concluded that 100 mg/body/day was the maximum tolerated dose (MTD) of
      S-1 and decided that the RD of S-1 was 80 mg/body/day.

PMID- 16897996
TI  - [Concurrent chemoradiotherapy (CRT) with S-1 and cisplatin (CDDP) in patients
      (pts) with locally advanced head and neck cancer (HNC)].
AB  - The standard care for unresectable locally advanced head and neck cancer (HNC) is
      concurrent chemoradiotherapy (CRT). Although there is no standard regimen of CRT,
      a platinum-based regimen has shown a better survival benefit than other regimens.
      The control arm in a randomized trial for unresectable locally advanced HNC is
      radiotherapy concurrent with CDDP (100 mg/m2, every 3 weeks), which has been
      considered to be too toxic for clinical practice in Western countries and has
      required frequent dose modifications. Because the Japanese also have been
      considered unable to tolerate this regimen, no prospective study of it has been
      conducted in Japan. Most Japanese patients with locally advanced head and neck
      cancer have received concurrent chemoradiotherapy with 5-FU and CDDP (70-80
      mg/m2). S-1 has shown high activity in HNC with a response rate of 34%.
      Furthermore, a combination of cisplatin and S-1 therapy for HNC has been reported
      to have good efficacy. With this rationale in mind, we conducted a phase I study
      of CRT with S-1 and CDDP for unresectable locally advanced squamous cell
      carcinoma of the head and neck. The CR rate was very promising, though
      preliminary, and warrants further investigation. The Japan Clinical Oncology
      Group (JCOG) is planning a multicenter phase II study of concurrent
      chemoradiotherapy with S-1 and CDDP for locally advanced unresectable HNC.

PMID- 16897997
TI  - [Adjuvant chemotherapy with S-1 for advanced head and neck carcinoma].
AB  - Most cases of head and neck squamous cell carcinoma (HNSCC) are in the advanced
      stages, resulting in a poor prognosis. To improve the poor outcome, adjuvant
      chemotherapy is indispensable for advanced cases with a high relapse risk after
      standard definitive treatments including surgery and/or radiotherapy. To define
      an adequate administration schedule in adjuvant chemotherapy with S-1, a
      controlled randomized study in multi-institutes was done. The results showed the
      2-week administration followed by 1-week rest was superior to the 4-week
      administration followed by the 2-week rest in terms of safety and efficacy. In
      the present paper, some problems of adjuvant chemotherapy were discussed, and the
      protocol was described in terms of a multi-institutional controlled randomized
      comparison study of S-1 versus UFT in an adjuvant chemotherapy setting for
      locally advanced HNSCC.

PMID- 16897998
TI  - [Phase I study of concurrent radiotherapy with S-1 for oral squamous cell
      carcinoma].
AB  - S-1 is a novel oral fluoropyrimidine inhibitory for dihydropyrimidine
      dehydrogenase (DPD). In the present study, we have examined the appropriate dose
      of S-1 in the combination with radiation and the safety and clinical efficacy.
      Radiation was given (2 Gy/day; 5 days/week) for a total of 60 Gy. S-1 was given
      orally every day for 2 weeks and then S-1 was stopped for 1 week. The levels were
      divided accordingly to the S-1 application as follows; level 0, 50 mg/m2/day;
      level 1, 65 mg/m2/day; level 2, 80 mg/m2/day. grade 3 toxicity of anorexia and
      the grade 3 toxicity increase in bilirubin level were observed in 2 cases of
      level 2. We decided that level 1 (65 mg/m2/day) was the recommended dose of the S
      1 application as observed in compliance and efficacy. This therapy is a useful
      concurrent chemo-radiotherapy which may improve the response rate and quality of
      life (QOL) of patients with oral squamous cell carcinoma.

PMID- 16897999
TI  - [Preoperative chemotherapy with S-1 and low-dose cisplatin for oral squamous cell
      carcinoma].
AB  - We investigated preoperative chemotherapy with S-1 and low-dose cisplatin for the
      untreated stage II-IV oral squamous cell carcinoma patients. The chemotherapy
      consisted of S-1 80 mg/m2/day (day 1-14) and CDDP 5 mg/m2/day (day 1-5 and day 8
      12) intravenous drip (less than 1 hour). In the second phase clinical trial of 44
      patients, the clinical response rate was 63.7% and the histological response rate
      by the Oboshi-Shimosato's evaluation was 61.4%. The main adverse events were
      myelosuppression and gastrointestinal disturbance such as nausea 36.4%, anorexia
      27.3%, neutropenia 25% and leukopenia 25%. Grade 3 and 4 adverse events were
      neutropenia 11.4%, leukopenia 9.1%, thrombocytopenia 4.5% and oligochromemia
      4.5%. The two-year overall survival rate was 92.6%. The advantages of this
      chemotherapy are high response rate, low adverse effects and not to prevent
      planned therapies such as surgery and radiation. These facts suggest that this
      chemotherapy is suitable for preoperative chemotherapy.

PMID- 16898000
TI  - [Phase II study of S-1, a novel oral fluorouracil, in advanced non-small-cell
      lung cancer].
AB  - The purpose of this study was to evaluate the efficacy and safety of a novel oral
      anticancer fluoropyrimidine derivative, S-1, in patients receiving initial
      chemotherapy for unresectable, advanced non-small-cell lung cancer (NSCLC).
      Between June 1996 and July 1998, 62 patients with NSCLC who received no previous
      chemotherapy for advanced disease were enrolled in this study. Fifty nine
      patients (22 in stage IIIB and 37 in stage IV) were eligible for the evaluation
      of efficacy and safety. S-1 was orally administered twice daily after meals.
      Three doses of S-1 were prescribed according to body surface area (BSA), so that
      they would be approximately equivalent to 80 mg/m2/day. One cycle of S-1
      consisted of consecutive administration for 28 days followed by a 2-week rest,
      and the cycle was repeated up to 4 times. The partial response (PR) rate of the
      eligible patients was 22.0% (13/59) (95% confidence interval: 12.3-34.7%). Grade
      4 neutropenia was observed in one of the 59 patients (1.7%). There were no
      irreversible, severe or unexpected toxicities. The median survival time (MST) of
      all of the patients was 10.2 months (95% confidence interval: 7.7-14.5 months),
      and the one-year survival rate was 41.1%. S-1 was considered to be an active
      single agent against NSCLC.

PMID- 16898001
TI  - [Combination chemotherapy with S-1 and cisplatin for non-small cell lung cancer].
AB  - S-1 is a newly developed oral anti-tumor agent, which contains 5-chloro-2, 4
      dihydroxypyridine and potassium oxonate to strengthen biological activities of 5
      fluorouracil. Response rate of S-1 for advanced non-small cell lung cancer was
      reported to be 12.5-22%. Response rate of combination chemotherapy with S-1 plus
      cisplatin (CDDP) was reported to be 47%, and the median survival time was 11
      months. Adverse events of the combination chemotherapy were milder than other
      combination chemotherapy described before. Therefore, S-1 plus CDDP combination
      chemotherapy is a future candidate for phase III clinical study.

PMID- 16898002
TI  - [Combination therapy with S-1 plus docetaxel (DOC) for previously treated
      patients with non-small cell lung cancer].
AB  - The present paper presents a review of the second-line treatment of non-small
      cell lung cancer (NSCLC) and reports a phase I study of the combination
      chemotherapy of docetaxel (DOC) and S-1 as second-line chemotherapy. Current
      options for the second-line treatment of NSCLC include cytotoxic drugs, such as
      DOC, pemetrexed, and targeted therapies. However, single-agent chemotherapy has
      shown limited activities. A new treatment approach is needed for this patient
      population. We hypothesized that combination chemotherapy of DOC and S-1 would be
      effective through the additive and synergistic activities. We performed a phase I
      clinical trial of this combination chemotherapy. S-1 was administered orally at a
      dose of 80 mg/m2 for 14 days, followed by a drug-free interval of a week (one
      cycle). The starting dose level (level 1) of DOC was set to 40 mg/m2, until a
      dose of 60 mg/m2 was reached at level 3. Three patients were treated with level
      2, in which the dose of DOC was increased up to 50 mg/m2. Two of 3 patients had
      grade 4 neutropenia, which was determined as dose-limiting toxicity. The dose
      level of DOC 40 mg/m2 on day 1 in combination with S-1 80 mg/m2 for 14 days of a
      three week cycle was recommended for a phase II study. Partial response was
      achieved in 4 of the 9 patients. This combined chemotherapy consisting of S-1 and
      DOC may prove effective for treating recurrent cases of NSCLC. A phase II study
      is ongoing.

PMID- 16898003
TI  - [Clinical benefit of S-1 in metastatic breast cancer].
AB  - Cytotoxic agents such as anthracycline or taxanes have provided a good clinical
      response for breast cancer patients, although they have failed to prolong the
      survival rate and to improve the quality of life (QOL) of these patients. On the
      other hand, cytostatic agents such as 5-fluorouracil (5-FU) have to be focused to
      accommodate a long term progression with respect to efficacy and the patients'
      QOL improvement. S-1 was a newly developed and orally administered fluorinated
      pyrimidine containing 1 M tegafur (FT) and two classes of a modulator, 5-chloro
      2,4-dihydroxypyrimidine (CDHP) and potassium oxonate (Oxo) at a molar ratio of FT
      : CDHP : Oxo= 1 : 0.4 : 1. Specific dose limiting factors such as neutropenia,
      diarrhea and stomatitis have been observed in a previous phase I study. Two phase
      II studies of 4 weeks treatment of S-1 (1 M tegafur-0.4 M gimestat-1 M otastat
      potassium) for the advanced or metastatic breast cancer patients were carried out
      in Japan. Among 108 evaluable patients for response, there were 10 complete
      response (CR) and 35 partial response (PR) with an overall response rate of 41.7%
      (95% confidence interval, 32.3-51.5%). The incidence of toxicity (> or = grade 3)
      was as followed: neutropenia 9.3%, anemia 0.9%, stomatitis 1.9% and
      nausea/vomiting 0.9%. The median follow-up period for patients was 802 days. S-1
      will be the new promising oral agent like a capecitabine which has been widely
      used as a third-line chemotherapy for the heavily treated breast cancer patients.

PMID- 16898004
TI  - [S-1 monotherapy for pancreatic cancer].
AB  - Early and late phase II studies of S-1 were conducted for the treatment of
      metastatic pancreatic cancer. In both trials, S-1 was administered at a dose of
      80 mg/m2/day. One course consisted of consecutive administration of S-1 for 28
      days, followed by 14 days of rest. This regimen was repeated every 6 weeks until
      the occurrence of progressive disease or unacceptable toxicities. The early phase
      II study demonstrated a response rate of 21.1% with a median survival time of 5.6
      months in 19 patients. The major drug-related adverse events were
      gastrointestinal toxicities like nausea, and anorexia, though most of them were
      tolerable and reversible. Other treatment-related adverse events, like ileus,
      colitis, and abdominal distension, were less frequent. The late phase II study
      confirmed favorable responces with a mild toxicity profile in 40 evaluable
      patients. S-1 is active and well tolerated in patients with metastatic pancreatic
      cancer. Randomized trials are warranted to determine the effectiveness of S-1 for
      the treatment of pancreatic cancer.

PMID- 16898005
TI  - [Long-term repeatable chemotherapy for patients with advanced pancreatic cancer].
AB  - At present, the advanced pancreatic cancer is known to be one of the most
      resistant malignancies on chemotherapy. To improve the efficacy of chemotherapy,
      we shifted the aim of chemotherapy from a tumor regression to long-term survival,
      and sought for a repeatable regimen with little toxicity. Some of the novel
      (repeatable) regimens used a combination of 5-FU/S-1, CDDP and paclitaxel
      performed for 10 patients with advanced pancreatic cancer (4 cases of Stage IVa
      and 6 cases of Stage IVb). As a result, the survival ratios of one and two years
      were 85.7% and 22.9%, respectively. The efficacy rate was 50% (5 cases of PR and
      5 cases of NC). Hematological adverse reactions over grade 3 were observed in 8
      out of 10 cases, although the decrease of platelet count was observed only in 2
      cases (grade 3 and 4). The majority of hematological adverse reactions over grade
      3 were leukocytepenia and anemia which were easy to control safely. All of non
      hematological adverse reactions were observed under grade 2 and did not disrupt
      the maintenance of chemotherapy.

PMID- 16898006
TI  - [Combination chemotherapy with gemcitabine and S-1 for advanced pancreatic
      cancer].
AB  - The incidence and mortality of pancreatic cancer has increased very rapidly in
      Japan. The five-year survival rate is still poor at less than 10%, because it is
      commonly considered to be linked to a high incidence of distant metastasis even
      at the initial diagnosis as well as to the tumor's resistance to anticancer
      agents. Although gemcitabine has been the most widely used chemotherapeutic agent
      in patients with advanced pancreatic cancer (APC), gemcitabine monotherapy has
      obvious limitations. Therefore, various combinations with other agents have been
      investigated to improving the survival of patients with APC. Under these
      circumstances, we conducted a phase I /II trial of gemcitabine with S-1, an oral
      fluorouracil derivative, to determine the maximum tolerated dose and to evaluate
      the activity and toxicity of such a combination in patients with APC. S-1 was
      administered orally twice daily each day for 14 days and gemcitabine on days 8
      and 15 of each cycle, and this cycle was repeated every 21 days. As a result, S-1
      30 mg/m2 orally twice daily and gemcitabine 1,000 mg/m2 were selected as the
      recommended dose. The toxicities observed were mainly hematological ones with
      mild non-hematological toxicities. An encouragingly high response rate was
      observed. This result is very promising, but the survival benefit in comparison
      with gemcitabine monotherapy needs to be confirmed in a future randomized
      clinical trial.

PMID- 16898007
TI  - [Radiotherapy combined with S-1 and cisplatin for locally advanced and metastatic
      esophageal cancer].
AB  - BACKGROUND: Chemoradiotherapy combined with 5-fluorouracil and cisplatin have
      been effective for the treatment of advanced esophageal cancer, but superior
      treatments are needed. We prospectively analyzed the efficacy of concurrent
      chemoradiotherapy using oral fluoropyrimidine (S-1) and cisplatin for the
      treatment of advanced esophageal cancer. METHODS: The treatment protocol was
      determined on a phase I study. The first chemoradiotherapy course consisted of 30
      Gy over 3 weeks, a daily oral administration of S-1 (80 mg/m2/day) for 2 weeks,
      and a 24-hour infusion of cisplatin (70 mg/M2) on day 8. A second course of
      chemoradiotherapy was performed after an interval of 2 weeks. RESULTS: Seventy
      one patients entered to this phase II study for five years (stage II: n=6, stage
      III: n=40, stage IV: n=25). All the stage II patients obtained a complete
      response, while 55% and 93% of the stage III patients and 20% and 76% of the
      stage IV patients obtained complete and partial responses, respectively. The
      major toxicity was myelosuppression. Eight patients (11%)developed a grade 4
      leukocytopenia. The median survival times were thirty-nine months and eleven
      months for the stage II + stage III and stage IV patients, respectively.
      CONCLUSION: Chemoradiotherapy combined with S-1 and cisplatin may be a promising
      treatment option for advanced esophageal cancer.

PMID- 16898008
TI  - [S-1 treatment against advanced HCC].
AB  - We have reported a remarkably high anti-tumor efficacy using intra arterial 5-FU
      infusion chemotherapy combined with subcutaneous interferon-alpha injection to
      treat advanced hepatocellular carcinoma (HCC) with portal vein thrombus. However,
      we have been confirming distant metastases along with a prognosis extension as
      hepatic lesions could possibly be controlled to a certain extent. Even though
      there has been no effective chemotherapy against hepatocellular carcinoma with
      distant metastases, we performed S-1 and interferon-alpha combination
      chemotherapy for the cases where good results were exhibited from interferon
      alpha combined with arterial 5-FU infusion. As a result, we confirmed CR in the
      anti-tumor effect against distant metastases with no severe adverse effects. It
      was suggested that a combination therapy of S-1 and interferon-alpha may be one
      of the most effective treatment modalities against advanced HCC with distant
      metastases.

PMID- 16898009
TI  - [The possibility of S-1 for the treatment of patients with urological cancers].
AB  - 5-FU is a major anti-tumor agent, and many clinical trials have been conducted to
      determine the efficacy of 5-FU and fluoropyrimidine derivatives for the treatment
      of urological cancers. S-1 is an oral fluoropyrimidine derivative that should be
      tested to demonstrate clinical efficacy for the treatment of urological cancers.
      Two phase II trials are being conducted to evaluate the efficacy and safety of S
      1 as a single agent therapy for patients with hormone-refractory prostate cancer
      (HRPC) and renal cell carcinoma (RCC).

PMID- 16898010
TI  - Stimulation of chlororespiration by heat and high light intensity in oat plants.
AB  - High irradiance and moderate heat inhibit the activity of the photosynthetic
      apparatus of oat (Avena sativa L.) leaves. The incubation of oat leaves under
      high light intensity in conjunction with high temperatures strongly decreased the
      maximal quantum yield of photosystem (PS) II, indicating the close synergistic
      effect of both stress factors on PS II inhibition and the subsequent irreversible
      damage to the photosynthetic apparatus. The PS I A/B protein levels remained
      similar to control values in leaves incubated under high light intensity or
      moderate heat, and decreased only when both stress factors were simultaneously
      applied. Immunoblot analysis of thylakoid membranes using specific antibodies
      raised against the NDH-K subunit of the thylakoidal NADH dehydrogenase complex
      (NADH DH) and against plastid terminal oxidase (PTOX) revealed an increase in the
      amount of both proteins in response to high light intensity and/or heat
      treatments. In addition, these stress treatments were seen to stimulate the
      activity of electron donation by NADPH and ferredoxin to plastoquinone, the PTOX
      activity in plastoquinone oxidation and the NADH DH activity in thylakoid
      membranes. Incubation with n-propyl gallate (an inhibitor of PTOX) inhibited the
      increase of NDH-K and PTOX levels under high light intensity and heat, and
      slightly stimulated the activity of electron donation by NADPH and ferredoxin to
      plastoquinone. Antimycin A (an inhibitor of cyclic electron flow) increased the
      NADH DH activity and preserved the levels of NDH-K and PTOX in thylakoid
      membranes from leaves incubated under high light intensity and heat. The up
      regulation of the PTOX and the thylakoidal NADH DH complex under these stress
      conditions supports a role for chlororespiration in the protection against high
      irradiance and moderate heat.

PMID- 16898011
TI  - Relationship between stem CO2 efflux, stem sap velocity and xylem CO2
      concentration in young loblolly pine trees.
AB  - We measured diel patterns of stem surface CO2 efflux (Es, micromol m(-2) s(-1)),
      sap velocity (vs, mm s(-1)) and xylem CO2 concentration ([CO2]) (Xs, %) in 8-year
      old loblolly pine trees during the spring to determine how vs and Xs influence
      Es. All trees showed a strong diel hysteresis between Es and stem temperature,
      where at a given temperature, Es was lower during the day than at night. Diel
      variations in temperature-independent Es were correlated with vs (R2= 0.54), such
      that at maximum vs, Es was reduced between 18 and 40%. However, this correlation
      may not represent a cause-and-effect relationship. In a subset of trees, vs was
      artificially reduced by progressively removing the tree canopy. Reducing vs to
      near zero had no effect on Es and did not change the diel hysteretic response to
      temperature. Diel Xs tended to decrease with vs and increase with Es, however, in
      defoliated trees, large increases in Xs, when vs approximately 0, had no effect
      on Es. We conclude that at this time of the year, Es is driven primarily by
      respiration of cambium and phloem tissues and that sap flow and xylem transport
      of CO2 had no direct influence on Es.

PMID- 16898012
TI  - Environmental and developmental effects on the biosynthesis of UV-B screening
      pigments in Scots pine (Pinus sylvestris L.) needles.
AB  - The major UV-B screening pigments of the epidermal layer of Scots pine (Pinus
      sylvestris) needles are flavonol 3-o-glycosides (F3Gs) esterified with
      hydroxycinnamic acids at positions 3" and 6". Acylation is the last step in
      biosynthesis and is catalysed by position-specific hydroxycinnamoyl transferases
      (3" and 6"HCT). The UV-B dependence of these enzyme activities was studied in
      primary needles of Scots pine seedlings grown under different UV-B conditions in
      environmentally controlled sun simulators. 6"HCT activity was induced upon UV-B
      irradiation while 3"HCT activity was not induced but showed high constitutive
      values. To investigate the biosynthesis of diacylated F3Gs during needle
      development under natural conditions, the HCT activities and metabolite contents
      were analysed in needles of field-grown mature pine trees. Accumulation of
      diacylated compounds as well as of 6"HCT activity occurred transiently in the
      first year of needle development only. In contrast, 3"HCT activity exhibited
      broad maxima in two consecutive years during needle growth. The data suggest that
      acylated F3Gs are first formed as soluble compounds which are then translocated
      into the cell wall to be bound by their hydroxycinnamoyl residues.

PMID- 16898013
TI  - Carbon isotopic composition and oxygen isotopic enrichment in phloem and total
      leaf organic matter of European beech (Fagus sylvatica L.) along a climate
      gradient.
AB  - This study investigated the influence of climate on the carbon isotopic
      composition (sigma13C) and oxygen isotopic enrichment (delta18O) above the source
      water of different organic matter pools in European beech. In July and September
      2002, sigma13C and delta18O were determined in phloem carbohydrates and in bulk
      foliage of adult beech trees along a transect from central Germany to southern
      France, where beech reaches its southernmost distributional limit. The data were
      related to meteorological and physiological parameters. The climate along the
      transect stretches from temperate [subcontinental (SC)] to submediterranean (SM).
      Both sigma13Cleaf and delta18Oleaf were representative of site-specific long-term
      environmental conditions. sigma13C of leaves collected in September was
      indicative of stomatal conductance, vapour pressure deficit (VPD) and radiation
      availability of the current growing season. delta18O was mainly correlated to
      mean growing season relative humidity (RH) and VPD. In contrast to the leaves,
      sigma13Cphloem varied considerably between July and September and was well
      correlated with canopy stomatal conductance (Gs) in a 2 d integral prior to
      phloem sampling. The relationship between sigma13C and delta18O in both leaves
      and phloem sap points, however, to a combined influence of stomatal conductance
      and photosynthetic capacity on the variation of sigma13C along the transect.
      delta18Ophloem could be described by applying a model that included 18O
      fractionation associated with water exchange between the leaf and the atmosphere
      and with the production of organic matter. Hence, isotope signatures can be used
      as effective tools to assess the water balance of beech, and thus, help predict
      the effects of climatic change on one of the ecologically and economically most
      important tree species in Central Europe.

PMID- 16898014
TI  - Estimating stomatal conductance with thermal imagery.
AB  - Most thermal methods for the study of drought responses in plant leaves are based
      on the calculation of 'stress indices'. This paper proposes and compares three
      main extensions of these for the direct estimation of absolute values of stomatal
      conductance to water vapour (gs) using infrared thermography (IRT). All methods
      use the measured leaf temperature and two environmental variables (air
      temperature and boundary layer resistance) as input. Additional variables
      required, depending on the method, are the temperatures of wet and dry reference
      surfaces, net radiation and relative humidity. The methods were compared using
      measured gs data from a vineyard in Southern Portugal. The errors in thermal
      estimates of conductance were of the same order as the measurement errors using a
      porometer. Observed variability was also compared with theoretical estimates of
      errors in estimated gs determined on the basis of the errors in the input
      variables (leaf temperature, boundary layer resistance, net radiation) and the
      partial derivatives of the energy balance equations used for the gs calculations.
      The full energy balance approach requires accurate estimates of net radiation
      absorbed, which may not be readily available in field conditions, so alternatives
      using reference surfaces are shown to have advantages. A new approach using a dry
      reference leaf is particularly robust and recommended for those studies where the
      specific advantages of thermal imagery, including its non-contact nature and its
      ability to sample large numbers of leaves, are most apparent. Although the
      results suggest that estimates of the absolute magnitude of gs are somewhat
      subjective, depending on the skill of the experimenter at selecting evenly
      exposed leaves, relative treatment differences in conductance are sensitively
      detected by different experimenters.

PMID- 16898015
TI  - Adaptation to high salinity in poplar involves changes in xylem anatomy and auxin
      physiology.
AB  - To investigate the physiological basis of salt adaptation in poplar, we compared
      the effect of salt stress on wood anatomy and auxin physiology of the salt
      resistant Populus euphratica and salt-sensitive Populus x canescens. Both poplar
      species showed decreases in vessel lumina associated with increases in wall
      strength in response to salt, however, in P. euphratica at three-fold higher salt
      concentrations than in P. x canescens. The predicted hydraulic conductivity of
      the wood formed under salt stress decreased in P. x canescens, while in P.
      euphratica, no significant effects of salt on conductivity and transpiration were
      observed. The concentration of free indole-3-acetic acid (IAA) decreased under
      salt stress in the xylem of both poplar species, but to a larger extent in P. x
      canescens than in P. euphratica. Only salt-treated P. euphratica exhibited an
      increase in IAA-conjugates in the xylem. Genes homologous to the auxin
      amidohydrolase ILL3 were isolated from the xylems of P. euphratica and P. x
      canescens. For functional analysis, the auxin-amidohydrolase from P. x canescens
      was overexpressed in Arabidopsis. Transgenic Arabidopsis plants were more
      resistant to salt stress than the wild-type plants. Increased sensitivity of the
      transgenic Arabidopsis to IAA-Leu showed that the encoded hydrolase used IAA-Leu
      as a substrate. These results suggest that poplar can use IAA-amidoconjugates in
      the stem as a source of auxin to balance the effects of salt stress on auxin
      physiology.

PMID- 16898016
TI  - Cadmium effect on oxidative metabolism of pea (Pisum sativum L.) roots. Imaging
      of reactive oxygen species and nitric oxide accumulation in vivo.
AB  - Growth of pea (Pisum sativum L.) plants with 50 microM CdCl2 for 15 d produced a
      reduction in the number and length of lateral roots, and changes in structure of
      the principal roots affecting the xylem vessels. Cadmium induced a reduction in
      glutathione (GSH) and ascorbate (ASC) contents, and catalase (CAT), GSH reductase
      (GR) and guaiacol peroxidase (GPX) activities. CuZn-superoxide dismutase (SOD)
      activity was also diminished by the Cd treatment, although Mn-SOD was slightly
      increased. CAT and CuZn-SOD were down-regulated at transcriptional level, while
      Mn-SOD, Fe-SOD and GR were up-regulated. Analysis of reactive oxygen species
      (ROS) and nitric oxide (NO) levels by fluorescence and confocal laser microscopy
      (CLM) showed an over-accumulation of O2*- and H2O2, and a reduction in the NO
      content in lateral and principal roots. ROS overproduction was dependent on
      changes in intracellular Ca+2 content, and peroxidases and NADPH oxidases were
      involved. Cadmium also produced an increase in salicylic acid (SA), jasmonic acid
      (JA) and ethylene (ET) contents. The rise of ET and ROS, and the NO decrease are
      in accordance with senescence processes induced by Cd, and the increase of JA and
      SA could regulate the cellular response to cope with damages imposed by cadmium.

PMID- 16898017
TI  - Conifer defence against insects: microarray gene expression profiling of Sitka
      spruce (Picea sitchensis) induced by mechanical wounding or feeding by spruce
      budworms (Choristoneura occidentalis) or white pine weevils (Pissodes strobi)
      reveals large-scale changes of the host transcriptome.
AB  - Conifers are resistant to attack from a large number of potential herbivores or
      pathogens. Previous molecular and biochemical characterization of selected
      conifer defence systems support a model of multigenic, constitutive and induced
      defences that act on invading insects via physical, chemical, biochemical or
      ecological (multitrophic) mechanisms. However, the genomic foundation of the
      complex defence and resistance mechanisms of conifers is largely unknown. As part
      of a genomics strategy to characterize inducible defences and possible resistance
      mechanisms of conifers against insect herbivory, we developed a cDNA microarray
      building upon a new spruce (Picea spp.) expressed sequence tag resource. This
      first-generation spruce cDNA microarray contains 9720 cDNA elements representing
      c. 5500 unique genes. We used this array to monitor gene expression in Sitka
      spruce (Picea sitchensis) bark in response to herbivory by white pine weevils
      (Pissodes strobi, Curculionidae) or wounding, and in young shoot tips in response
      to western spruce budworm (Choristoneura occidentalis, Lepidopterae) feeding.
      Weevils are stem-boring insects that feed on phloem, while budworms are foliage
      feeding larvae that consume needles and young shoot tips. Both insect species and
      wounding treatment caused substantial changes of the host plant transcriptome
      detected in each case by differential gene expression of several thousand array
      elements at 1 or 2 d after the onset of treatment. Overall, there was
      considerable overlap among differentially expressed gene sets from these three
      stress treatments. Functional classification of the induced transcripts revealed
      genes with roles in general plant defence, octadecanoid and ethylene signalling,
      transport, secondary metabolism, and transcriptional regulation. Several genes
      involved in primary metabolic processes such as photosynthesis were down
      regulated upon insect feeding or wounding, fitting with the concept of dynamic
      resource allocation in plant defence. Refined expression analysis using gene
      specific primers and real-time PCR for selected transcripts was in agreement with
      microarray results for most genes tested. This study provides the first large
      scale survey of insect-induced defence transcripts in a gymnosperm and provides a
      platform for functional investigation of plant-insect interactions in spruce.
      Induction of spruce genes of octadecanoid and ethylene signalling, terpenoid
      biosynthesis, and phenolic secondary metabolism are discussed in more detail.

PMID- 16898018
TI  - 13CO2 pulse-labelling of photoassimilates reveals carbon allocation within and
      between tree rings.
AB  - Post-photosynthetic fractionation processes during translocation, storage and
      remobilization of photoassimilate are closely related to intra-annual sigma13C of
      tree rings, and understanding how these processes affect tree-ring sigma13C is
      therefore indispensable for improving the quality of climate reconstruction. Our
      first objective was to study the relationship between translocation path and
      phloem grain. We pulse-labelled a branch of Larix gmelinii (Rupr.) Rupr. and
      later analysed the sigma13C distribution in the stem. A 13C spiral translocation
      path closely related to the spiral grain was observed. Our second objective was
      to study the use of remobilized storage material for earlywood formation in
      spring, which is a suspected cause of the autocorrelation (correlation of ring
      parameters to the climate in the previous year) observed in (isotope)
      dendroclimatology. We pulse-labelled whole trees to study how spring, summer and
      autumn photoassimilate is later used for both earlywood and latewood formation.
      Analysis of intra-annual sigma13C of the tree rings formed after the labelling
      revealed that earlywood contained photoassimilate from the previous summer and
      autumn as well as from the current spring. Latewood was mainly composed of
      photoassimilate from the current year's summer/autumn, although it also relied on
      stored material in some cases. These results emphasize the need for separating
      earlywood and latewood for climate reconstruction work with narrow boreal tree
      rings.

PMID- 16898019
TI  - Using nutritional indices to study LOX3-dependent insect resistance.
AB  - Induced resistance to biotic attackers is thought to be mediated by responses
      elicited by jasmonic acid (JA), a subset of which are lipoxygenase 3 (LOX3)
      dependent. To understand the importance of LOX3-mediated insect resistance, we
      analysed the performance of Manduca sexta larvae on wild-type (WT) and on
      isogenic Nicotiana attenuata plants silenced in NaLOX3 expression and JA
      signalling, and we used Waldbauer nutritional indices to measure the pre- and
      post-ingestive effects. LOX3-mediated defenses reduced larval growth, consumption
      and frass production. These defenses reduced how efficiently late-instar larvae
      converted digested food to body mass (ECD). In contrast, LOX3-mediated defenses
      decreased approximate digestibility (AD) in early instar larvae without affecting
      the ECD and total food consumption. Larvae of all instars feeding on defended WT
      plants behaviourally compensate for their reduced body mass by consuming more
      food per unit of body mass gain. We suggest that larvae feeding on plants
      silenced in NaLOX3 expression (as-lox) initially increase their AD, which in turn
      enables them to consume more food in the later stages and consequently, to
      increase their ECD and efficiency of conversion of ingested food (ECI). We
      conclude that N. attenuata's oxylipin-mediated defenses are important for
      resisting attack from M. sexta larvae, and that Waldbauer nutritional assays
      reveal behavioural and physiological counter responses of insects to these plant
      defenses.

PMID- 16898020
TI  - Guard cells in albino leaf patches do not respond to photosynthetically active
      radiation, but are sensitive to blue light, CO2 and abscisic acid.
AB  - Stomatal openings can be stimulated by light through two signalling pathways. The
      first pathway is blue light specific and involves phototropins, while the second
      pathway mediates a response to photosynthetically active radiation (PAR). This
      second pathway was studied with the use of albino Vicia faba plants and
      variegated leaves of Chlorophytum comosum. Treatment of V. faba with norflurazon
      (Nf) inhibits the synthesis of carotenoids and leads to albino leaves with guard
      cells that lack functional green chloroplasts. Guard cells in albino leaf patches
      of C. comosum, however, do contain photosynthetically active chloroplasts.
      Stomata in albino leaf patches of both plants did not respond to red light,
      although blue light could still induce stomatal opening. This shows that the
      response to PAR is not functioning in albino leaf patches, even though guard
      cells of C. comosum harbour chloroplasts. Stomata of Nf-treated plants still
      responded to CO2 and abscisic acid (ABA). The size of Nf-treated guard cells was
      increased, but impalement studies with double-barrelled microelectrodes revealed
      no changes in ion-transport properties at the plasma membrane of guard cells.
      Blue light could hyperpolarize albino guard cells by triggering outward currents
      with peak values of 37 pA in albino plants and 51 pA in green control cells.
      Because of the inhibition of carotenoid biosynthesis, Nf-treated V. faba plants
      contained only 4% of the ABA content found in green control plants. The ABA dose
      dependence of anion channel activation in guard cells was shifted in these
      plants, causing a reduced response to 10 microM ABA. These data show that despite
      the dramatic changes in physiology caused by Nf, the gross responsiveness of
      guard cells to blue light, CO2 and ABA remains unaltered. Stomata in albino leaf
      patches, however, do not respond to PAR, but require photosynthetically active
      mesophyll cells for this response.

PMID- 16898021
TI  - Desiccation of the resurrection plant Craterostigma plantagineum induces dynamic
      changes in protein phosphorylation.
AB  - Reversible phosphorylation of proteins is an important mechanism by which
      organisms regulate their reactions to external stimuli. To investigate the
      involvement of phosphorylation during acquisition of desiccation tolerance, we
      have analysed dehydration-induced protein phosphorylation in the desiccation
      tolerant resurrection plant Craterostigma plantagineum. Several dehydration
      induced proteins were shown to be transiently phosphorylated during a dehydration
      and rehydration (RH) cycle. Two abundantly expressed phosphoproteins are the
      dehydration- and abscisic acid (ABA)-responsive protein CDeT11-24 and the group 2
      late embryogenesis abundant (LEA) protein CDeT6-19. Although both proteins
      accumulate in leaves and roots with similar kinetics in response to dehydration,
      their phosphorylation patterns differ. Several phosphorylation sites were
      identified on the CDeT11-24 protein using liquid chromatography-tandem mass
      spectrometry (LCMS/MS). The coincidence of phosphorylation sites with predicted
      coiled-coil regions leads to the hypothesis that CDeT11-24 phosphorylations
      influence the stability of coiled-coil interactions with itself and possibly
      other proteins.

PMID- 16898022
TI  - Mechanical reinforcement of tracheids compromises the hydraulic efficiency of
      conifer xylem.
AB  - Wood structure and function of juvenile wood from 18 conifer species from four
      conifer families (Araucariaceae, Cupressaceae, Pinaceae and Podocarpaceae) were
      examined for a trade-off between wood reinforcement and hydraulic efficiency.
      Wood density and tracheid 'thickness-to-span' ratio were used as anatomical
      proxies for mechanical properties. The thickness:span represented the ratio of
      tracheid double wall thickness to lumen diameter. Hydraulic resistivity (R) of
      tracheids on a cross-sectional area basis (RCA) increased over 50-fold with
      increasing density and thickness:span, implying a strength versus efficiency
      conflict. The conflict arose because density and thickness:span were increased by
      narrowing tracheid diameter rather than by thickening walls, which may be
      developmentally difficult. In the Pinaceae and Cupressaceae species, density and
      thickness:span correlated strongly with protection from drought-induced embolism,
      suggesting that mechanical strength was required in part to withstand tracheid
      collapse by negative sap pressure. These species showed a corresponding trade-off
      between increasing RCA and embolism protection. In contrast, species of
      Podocarpaceae and Araucariaceae were overbuilt for their embolism protection and
      were hydraulically inefficient, having greater density, thickness:span and RCA,
      none of which were correlated with vulnerability to embolism.

PMID- 16898024
TI  - How do leaf hydraulics limit stomatal conductance at high water vapour pressure
      deficits?
AB  - A reduction in leaf stomatal conductance (g) with increasing leaf-to-air
      difference in water vapour pressure (D) is nearly ubiquitous. Ecological
      comparisons of sensitivity have led to the hypothesis that the reduction in g
      with increasing D serves to maintain leaf water potentials above those that would
      cause loss of hydraulic conductance. A reduction in leaf water potential is
      commonly hypothesized to cause stomatal closure at high D. The importance of
      these particular hydraulic factors was tested by exposing Abutilon theophrasti,
      Glycine max, Gossypium hirsutum and Xanthium strumarium to D high enough to
      reduce g and then decreasing ambient carbon dioxide concentration ([CO2]), and
      observing the resulting changes in g, transpiration rate and leaf water
      potential, and their reversibility. Reducing the [CO2] at high D increased g and
      transpiration rate and lowered leaf water potential. The abnormally high
      transpiration rates did not result in reductions in hydraulic conductance.
      Results indicate that low water potential effects on g at high D could be
      overcome by low [CO2], and that even lower leaf water potentials did not cause a
      reduction in hydraulic conductance in these well-watered plants. Reduced g at
      high D in these species resulted primarily from increased stomatal sensitivity to
      [CO2] at high D, and this increased sensitivity may mediate stomatal responses to
      leaf hydraulics at high D.

PMID- 16898023
TI  - Differences in construction costs and chemical composition between deciduous and
      evergreen woody species are small as compared to differences among families.
AB  - We tested to what extent differences in construction costs (CC) and chemical
      composition of woody species are attributed to leaf habit. Eight evergreen and
      eight deciduous species belonging to six families were selected to form eight
      phylogenetic independent contrasts (PICs). The plants were grown from seed in a
      glasshouse. Differences in leaf, stem and root CC between evergreen and deciduous
      species were minor, the proportion of variance explained by leaf habit generally
      being less than 6%. Surprisingly, differences in leaf chemical composition
      between deciduous and evergreen species were small as well. Variation in CC and
      chemical composition among families was substantial, the factor 'family'
      explaining 50-85% of variance. We therefore conclude that in this case, phylogeny
      is a more important factor than functional group. Leaves of the fast-growing
      species in this experiment showed high levels of minerals, organic acids,
      proteins and lipids, whereas leaves of the slow-growing species had higher
      concentrations of soluble phenolics, lignin as well as higher carbon/nitrogen
      (C/N) ratio. These relationships suggest a trade-off between growth and defence.
      In contrast, CC of leaves, stems, roots or whole plants showed no or only a weak
      correlation with relative growth rate (RGR). The C/N ratio of the leaves is an
      easily measured parameter that correlated strongly in a negative way with the RGR
      of the plants and reflected better the balance between investment in structure
      and physiological functioning than CC.

PMID- 16898025
TI  - Increased C availability at elevated carbon dioxide concentration improves N
      assimilation in a legume.
AB  - Plant growth is typically stimulated at elevated carbon dioxide concentration
      ([CO2]), but a sustained and maximal stimulation of growth requires acquisition
      of additional N in proportion to the additional C fixed at elevated [CO2]. We
      hypothesized that legumes would be able to avoid N limitation at elevated [CO2].
      Soybean was grown without N fertilizer from germination to final senescence at
      elevated [CO2] over two growing seasons under fully open-air conditions,
      providing a model legume system. Measurements of photosynthesis and foliar
      carbohydrate content showed that plants growing at elevated [CO2] had a c. 25%
      increase in the daily integral of photosynthesis and c. 58% increase in foliar
      carbohydrate content, suggesting that plants at elevated [CO2] had a surplus of
      photosynthate. Soybeans had a low leaf N content at the beginning of the season,
      which was a further c. 17% lower at elevated [CO2]. In the middle of the season,
      ureide, total amino acid and N content increased markedly, and the effect of
      elevated [CO2] on leaf N content disappeared. Analysis of individual amino acid
      levels supported the conclusion that plants at elevated [CO2] overcame an early
      season N limitation. These soybean plants showed a c. 16% increase in dry mass at
      final harvest and showed no significant effect of elevated [CO2] on leaf N,
      protein or total amino acid content in the latter part of the season. One
      possible explanation for these findings is that N fixation had increased, and
      that these plants had acclimated to the increased N demand at elevated [CO2].

PMID- 16898026
TI  - Effects of Rubisco kinetics and Rubisco activation state on the temperature
      dependence of the photosynthetic rate in spinach leaves from contrasting growth
      temperatures.
AB  - Recently, several studies reported that the optimum temperature for the initial
      slope [IS(Ci)] of the light-saturated photosynthetic rate (A) versus
      intercellular CO2 concentration (Ci) curve changed, depending on the growth
      temperature. However, few studies compare IS(Ci) with ribulose 1,5-bisphosphate
      carboxylase/oxygenase (Rubisco) properties. Here, we assessed Rubisco activation
      state and in vitro Rubisco kinetics, the main determinants of IS(Ci), in spinach
      leaves grown at 30/25 [high temperature (HT)] and 15/10 degrees C [low
      temperature (LT)]. We measured Rubisco activation state and A at a CO2
      concentration of 360 microL L(-1) (A360) at various temperatures. In both HT and
      LT leaves, the Rubisco activation state decreased with increasing temperatures
      above the optimum temperatures for A360, while the activation state remained high
      at lower temperatures. To compare Rubisco characteristics, temperature
      dependences of the maximum rate of ribulose 1,5-bisphosphate (RuBP) carboxylation
      (Vcmax), specificity factor (Sc/o) and thermal stability were examined. We also
      examined Vcmax, and thermal stability in the leaves that were transferred from HT
      to LT conditions and were subsequently kept under LT conditions for 2 weeks (HL).
      Rubisco purified from HT, LT and HL leaves are called HT, LT and HL Rubisco,
      respectively. Thermal stabilities of LT and HL Rubisco were similar and lower
      than that of HT Rubisco. Both Vcmax and Sc/o in LT Rubisco were higher than those
      of HT Rubisco at low temperatures, while these were lower at high temperatures.
      Vcmax in HL Rubisco were similar to those of LT Rubisco at low temperatures, and
      to those of HT Rubisco at high temperatures. The predicted photosynthetic rates,
      taking account of the Rubisco kinetics and the Rubisco activation state, agreed
      well with A360 in both HT and LT leaves. This study suggests that photosynthetic
      performance is largely determined by the Rubisco kinetics at low temperature and
      by Rubisco Kinetics and the Rubisco activation state at high temperature.

PMID- 16898027
TI  - Hereditary spastic paraplegias.

PMID- 16898028
TI  - Disorders of appetite and eating.

PMID- 16898029
TI  - A descriptive clinical evaluation of arthroscopic synovectomy in rheumatoid
      knees: a prospective study.
AB  - OBJECTIVE: To evaluate the clinical outcome of arthroscopic synovectomy for
      persistent rheumatoid synovitis of the knee joints. DESIGN: Prospective clinical
      study. SETTING: Kasturba Medical College Hospital, Manipal. PATIENTS: Fifty two
      knee joints in 46 patients. MEASUREMENTS: The effect of the procedure and its
      influence in the progression of the disease process on knee joints were assessed
      in terms of reduction of pain, improvement in range of motion, improvement in
      functional activity and recurrence of synovitis with effusion. RESULTS: During
      the average follow up period of 5 years, the patients showed appreciable
      improvement (90% of knee joints) until 3 years of follow up. At the end of 5
      years of follow up, it reduced to about 75%. CONCLUSIONS: Arthroscopic
      synovectomy along with medical treatment can control the disease process and
      preserve the knee joint function for up to 3 years.

PMID- 16898030
TI  - Anti-tuberculosis drug inducd hepatitis - a Sri Lankan experience.
AB  - OBJECTIVE: To assess the incidence of anti-tuberculosis (TB) drug induced
      hepatitis (AIH) in Sri Lankan patients, determine risk factors of AIH, and to
      address management options in AIH. DESIGN: A prospective study. SETTING: Chest
      Hospital, Welisara, Sri Lanka, from April 2001 to April 2002. PATIENTS: Seven
      hundred and eighty three patients with a confirmed diagnosis of TB and resident
      in the Colombo and Gampaha districts who presented to Chest Hospital, Welisara,
      Sri Lanka. METHODS: WHO recommended treatment was commenced in all cases. AIH was
      diagnosed when patients complained of decreased appetite with nausea or vomiting
      and elevated serum bilirubin (SB; >1.1 mg/dL) or elevated serum alanine
      transferase (ALT; > 3 times upper limit of normal). RESULTS: Of 783 enrolled
      patients, 74 (9.5%) developed AIH, the majority (58%) developing AIH within the
      first 2 weeks of the intensive phase of treatment. AIH was more common among
      patients over 60 years (p = 0.018), who developed pulmonary TB (p = 0.028), and
      in patients weighing 33-55 kg (p = 0.004). Age, weight and rifampicin overdosage
      were significant predictors of AIH. Of the 74 AIH patients, standard treatment
      was restarted in 60, treatment modified in six, two defaulted and six died.
      CONCLUSIONS: The incidence of AIH in Sri Lanka is 9.5% in treated patients. AIH
      was associated with age, low body weight and rifampicin overdosage.

PMID- 16898031
TI  - Psychological reactions and coping strategies of Sri Lankan women carrying
      fetuses with lethal congenital malformations.
AB  - INTRODUCTION: Termination of pregnancy is a popular option for pregnancies
      complicated by lethal congenital malformations (LCMs). In Sri Lanka, where
      abortion laws are restrictive, this is not available. We studied the
      psychological responses and coping strategies of women who had to continue their
      pregnancies knowing the baby had a LCM. SETTING: A teaching hospital in Sri
      Lanka. STUDY DESIGN: Qualitative inquiry. METHOD: We conducted a semi-structured
      interview of 10 women whose fetuses were diagnosed to have a LCM. RESULTS: All
      women showed a grief reaction on hearing the news and were distressed about
      having to carry a futile pregnancy. Eight women were grateful they knew of the
      abnormality because it prepared them for the birth better, while the other two
      wished they had not known. They all found having to share facilities with
      'normal' women to be painful. Seven women who received 'routine' antenatal care
      felt that the doctors were ill-equipped to deal with their situation. All felt
      that abortion should be legalised for LCMs. All engaged in religious rites
      believed to have miraculous powers, hoping that these will result in a normal
      baby. Two required specialised counselling. CONCLUSIONS: The diagnosis of a LCM
      causes severe distress and psychological reactions, which the staff dealing with
      these women should be aware of. Ideally, they should be provided care with
      minimum contact with other women, taking into account the futility of the
      pregnancy. Engagement in religious rites, even though with unreal expectations,
      may possibly help them in the long term bereavement process.

PMID- 16898032
TI  - Admission to medical schools in Sri Lanka: predictive validity of selection
      criteria.
AB  - OBJECTIVE: To assess the extent to which current selection criteria predict
      success in Sri Lanka's medical schools. METHODS: The study sample consisted of
      all students selected to all six medical schools in two consecutive entry
      cohorts. The aggregate marks of these students at the General Certificate of
      Education (GCE) Advanced Level examination, the district of entry, admission
      category, candidate type (school/private) and gender, were identified as entry
      point variables. Success in medical school was measured in four ways: the ability
      to pass the first summative examination and the final examination at the first
      attempt, and obtaining honours in either examination. Multivariate analysis using
      logistic regression was used to assess the extent to which these entry point
      factors predict variability in outcome measures. RESULTS: Aggregate scores among
      the 1740 students in the study sample ranged from 212 to 356, with a median of
      285. The male:female ratio was 1.4:1. Private candidates (taking the examination
      for the third time) accounted for 22% of students. Being a school candidate,
      female and having a higher aggregate score, were the only independent predictors
      of success for all four outcome measures. The aggregate score alone accounted for
      only 1-7% of the variation in performance in medical school. CONCLUSIONS: Marks
      obtained at the A Level examination (the only academic criterion currently used
      for selection of medical students in Sri Lanka) is a poor predictor of success in
      medical school.

PMID- 16898033
TI  - Do we need to use nitric oxide in preterm babies in developing countries?
AB  - Neonatal care in developing nations is advancing rapidly. There is an increasing
      tendency to include nitric oxide in the therapeutic armamentarium. But the
      opinion regarding its use remains divided among neonatologists even in the
      western world. Nitric oxide has an established role in the management of
      persistent pulmonary hypertension in term neonates. However, the use of nitric
      oxide in preterm neonates has been controversial and the Cochrane review updated
      in 2001 did not give conclusive answers. There have been adequately powered multi
      centre trials recently on the issue, planned to resolve the controversy. The
      present communication highlights the salient features and conclusions drawn from
      these trials.

PMID- 16898035
TI  - Deshamanya Dr. PR Anthonis.

PMID- 16898034
TI  - The diabetes epidemic in Sri Lanka - a growing problem.
AB  - Diabetes mellitus, which was once considered a disease of the developed world,
      has become a worldwide pandemic, with two thirds of the global diabetic
      population living in the developing countries. Local studies show a definite
      upward trend in the prevalence of diabetes mellitus. The earliest available study
      on a rural community in 1990 reported a prevalence of 2.5%. The largest-ever
      study on the diabetes prevalence in Sri Lanka was published in 2005. It showed a
      prevalence of 14.2% among males and 13.5% among females. The World Health
      Organisation and the International Diabetic Federation estimates and forecasts
      are much lower than the available local prevalence rates, and what may be
      predicted from the prevalence rates in South India. Further research is necessary
      to investigate the exact underlying mechanisms for the South Asian epidemic.
      Wider preventive programmes need to be urgently implemented to stem the tide.

PMID- 16898036
TI  - Cystic fibrosis. Pseudomonas aeruginosa infection.

PMID- 16898038
TI  - A case of Proteus syndrome (elephant man).

PMID- 16898037
TI  - Paroxysmal kinesigenic dyskinesia.
AB  - Paroxysmal kinesigenic dyskinesia (PKD) is a rare disorder characterised by brief
      and frequent attacks of abnormal involuntary movements induced by sudden
      movement. This disorder has not been reported previously in Sri Lanka. We studied
      six patients with respect to clinical presentation, aetiology, family history and
      response to treatment, and describe the Sri Lankan patterns of this illness. All
      the patients were males and the age at onset was from 11 to 22 years. The
      involuntary movements in all were dystonic and affected one or both sides,
      involving the face in the majority. All had difficulty in speaking during the
      attacks. One patient had an occasional attack during exercise. In all, the
      illness was sporadic, none had a family history of a similar illness and in none
      was it due to a secondary cause. The attacks usually lasted 10-60 seconds, and
      occurred up to 20 times a day. All patients responded well to anticonvulsants.
      PKD in Sri Lanka has a pattern similar to that described worldwide.

PMID- 16898039
TI  - A giant neurofibroma.

PMID- 16898040
TI  - The validity of fasting blood glucose and post-prandial blood glucose measurement
      as an index of glycaemic control in Sri Lankan patients with type 2 diabetes.

PMID- 16898041
TI  - Knowledge, attitudes and practices regarding postpartum contraception among 100
      mother-father pairs leaving a Sri Lankan maternity hospital after childbirth.

PMID- 16898042
TI  - Exposure to acetylcholinesterase-inhibiting pesticides and chronic renal failure.

PMID- 16898043
TI  - Carer burden in dementia.

PMID- 16898045
TI  - [Stress and health: role of personality. Presentation of some tools for
      personality evaluation].

PMID- 16898047
TI  - [Analysis technique of survey data. Example with artificial insemination and
      anonymous donors, or how to clarify a debate in society].

PMID- 16898048
TI  - [Humour in the nurse-patient relation: a review of the literature].
AB  - Humour holds an important and almost omni-present place in human communication.
      Research and reflection on humour have tried to define the scope of its causes,
      its effects, its mechanisms of action and production, its purposes and its uses.
      This article aims at drawing up a general description of scientific studies
      dealing with humour carried out in the context of the nurse-patient communication
      and at making an analysis of it from the fixed theory of Strauss and Corbin
      (2001) to derive the characteristics, conditions of use and consequences as much
      in the patient's as in the nurse's. The results obtained prove that humour in
      care is contextual, situational and spontaneous. There are conditions of use of
      humour which are connected with the nurse, with the patient, with their relation
      and with the situation. For the patient and in the nurse-patient relation, humour
      has psychological consequences. It can be or become a coping mechanism to face
      stress and improve the quality of communication.

PMID- 16898046
TI  - [The question of observation scales in applied human sciences in the domain of
      health].

PMID- 16898049
TI  - [Factors linked to premature leaving of the nursing profession. Confirmation of
      the impact one year later. Longitudinal analyses of nurses. PRESST/NEXT study].
AB  - BACKGROUND: The organization of French medical institutions is changing, and the
      nursing personnel can encounter difficulties of adaption to these changes. The
      results of 2 questionnaires of the PRESST/NEXT study relative to working
      conditions (respectively, the questionnaires "Q0" and "Q12"), sent in a year
      interval to a sample of nurses were compared. METHODS: Three samples were made
      up: a sample of 5376 nurses having answered the initial questionnaire (Q0); a
      sample of 2627 nurses having answered the questionnaire sent one year after
      (Q12), and working in the same establishment; a group of 208 nurses having
      answered the questionnaire "Qex", specific to nurses who left their
      establishment. RESULTS: Among nurses who answered the "Qex", approximately 1/5 of
      nurses chose to leave the profession definitively or temporarily before the
      retirement age; of these, almost 13% began a new work not in the healthcare
      sector. Seven factors are significantly related to the intention of leaving the
      profession: Dissatisfaction regarding professional prospects (Q0: OR = 3.1 and
      Q12: OR = 2.82); Difficulties assuming the family responsabilities (Q0: OR = 1.36
      and Q12: OR = 2.10); Mental health disorders for nurses not followed medically
      (Q0: OR = 1.76 and Q12: OR = 1.47), and for nurses receiving care for this (Q0 :
      OR = 1.90 and Q12: OR = 1.77); Dissatisfaction concerning the psychological
      support available at work (Q0: OR = 1.57 and Q12: OR = 1.87); Tiredness (Q0 : OR
      = 1.40 and Q12: OR = 1.6); Musculo-skeletal disorders diagnosed by doctor (Q0: OR
      = 1.32 and Q12: OR = 1.61); Dissatisfaction concerning the use of competences
      (Q0: OR = 1.27 and Q12: OR = 1.97). CONCLUSION: These results raise questions as
      to the benefits of new management which promotes flexibility in work and
      schedules, and which reduces the possibilities of support within the nursing
      teams. This type of management implies uncertainty for nurses as far as the
      technical aspects of their work are concerned, and a lack of time for the
      education and follow-up of patients.

PMID- 16898050
TI  - [From giving care to thinking care or the difficulty of putting nursing practice
      "into words"].
AB  - My experience as a nurse and as a trainer brought me to wonder about the nursing
      practices in terms of Therapeutic Education of the Patient (TEP). Various
      studies, professional articles and a report of the Ministry of Health show a gap
      between an optimal educational approach experiences by nurses and the reality of
      their practice in TEP, namely a very injuctive and prescriptive practice, the
      ineffectiveness of which in therapeutic education with the patients is well
      known. Putting experience into words consists in transforming the events of the
      located action, in making its progress understandable so as to make the action
      aware and an object of reflection; to move then to a stage of elaboration of
      cognitive schemas which account for the understanding of encountered situations
      and undertaken professional practices. This necessary work of conceptualization
      allows some formalization which help to transpose experience to other situations
      and to act as a professional. On looking at this process of the experience
      elaborated by G. THE BOTERF, I shall try to show how nurses put their experience
      into words as part of TEP and to track down where their difficulties to think
      over a more efficient educational approach are situated. I shall rely on
      conversations carried on by nurses training as part of a master's thesis with
      nurses practising TEP.

PMID- 16898051
TI  - [What place can the health executive hold in the internal contract process?].
AB  - The current context of cost control relative to health expenditures forces
      hospitals to wonder about their management style. Therefore, the question of the
      efficiency of the health system is raised. Would the formalization by contract
      bring the beginnings of an answer? This is what its growing development within
      numerous public health establishments leads one to suppose, thus signing an
      evolution towards some new "medical and administrative" governance. Through this
      article, I therefore suggest to you a questioning on the essence of the
      contractual method, its stakes, its limits and especially a projective approach
      on the consequences of this management method considering the "health executive"
      function. As the stake in this reflection is to highlight the fact that if the
      health executive has a place acknowledged in the internal formalization by
      contract, its competence will constitute an increase in value in the contractual
      process. Indeed, this questioning seems important to me and this, all the more as
      the ordinance dated May 2, 2005 including "various arrangements relative to the
      functioning of public health establishments and modifying the public health
      code", stipulates that public hospitals should resort to the method of internal
      formalization by contract in setting up centres of activity and this, at the
      latest, before December 31, 2006.

PMID- 16898052
TI  - Medicare Part D: where we are and where we're going.
AB  - Achieving optimum outcomes for our patients clearly is going to require more than
      making the correct diagnosis and writing the right prescription. If patients
      cannot access the prescriptions needed to achieve the desired outcome, providers
      will be judged falling short of the mark. Achieving optimum outcomes requires not
      only understanding Medicare Part D, but also using this knowledge to develop an
      efficient and effective office system to gain access to all medically necessary
      prescriptions.

PMID- 16898053
TI  - The transition to Medicare Part D and the new senior care landscape.
AB  - The landscape of coverage for prescription drugs for Medicare beneficiaries has
      dramatically changed as a result of Medicare Part D. As regulations were drafted
      to govern this program, the federal government's fear was that because pharmacy
      benefit managers had never gone at risk for the management of medications, plans
      would be reluctant to enter the new arena of Medicare drug coverage. Of course,
      that has not happened as hundreds of various plans have entered this market,
      including a new form of managed care plan referred to as a "special needs plan".
      The landscape of health care has changed and will continue to change as Medicare
      Part D changes, both as the result of competitive market forces and regulatory
      actions.

PMID- 16898055
TI  - Medicare Part D: exceptions and appeals process.
AB  - Once enrolled in a Medicare Part D prescription plan, the focus changes to access
      to medically necessary medications through the prescription plan. In many
      situations, this will involve the exceptions and appeals process. Each Medicare
      plan has its own drug formulary and differentiates itself through various
      parameters within those formularies. The federal government has rules in place
      for what may or may not be covered in a formulary, and has specified parameters
      for an exceptions and appeals process. It is the responsibility of the patient,
      along with his or her physician, to learn about and take advantage of mechanisms
      built into the system to ensure access to medically necessary medications. As
      physician reimbursement moves to an outcome-based through pay-for-performance
      system, physicians will have a financial incentive for assuring that their
      patients receive the necessary medications.

PMID- 16898054
TI  - Senior enrollment in Medicare Part D.
AB  - The obvious starting point for beneficiaries to take advantage of the Medicare
      Part D program is to enroll in a plan that best meets their needs. Medicare
      beneficiaries that currently have creditable coverage (as good as Medicare Part
      D) should, in most situations, stay with their plan. Those without coverage
      should carefully assess the importance of joining a plan. Important factors to
      consider include being locked out of a plan from the end of the initial
      enrollment period, May 15, 2006, until the next open enrollment period, Nov. 15,
      2006, through Dec. 31, 2006, with the new plan becoming effective Jan. 1, 2007;
      the late enrollment penalty of a 1 percent increase in premium for every month
      without coverage; and the lost opportunity in not taking advantage of having
      coverage, especially for those eligible for the low-income subsidy.

PMID- 16898056
TI  - Navigating Medicare drug coverage: Part B vs. Part D.
AB  - One of the gray areas of Medicare Part D coverage is determining when a
      prescription falls under Part D and when it falls under Part B. Most Part B drug
      spending is for drugs billed by a physician and provided incident to the
      physician's services for a Medicare patient. Medicare Part D medications are
      dispensed via a prescription and are usually self-administered. Here are examples
      of situational rules that determine whether a patient is covered under Part B or
      Part D. Many situations exist where a particular drug for a specific patient is
      covered under both Part B and Part D, albeit with different delivery and cost
      sharing aspects. Understanding which applies when is important to gaining access
      to medically necessary prescriptions for patients. Giving this information to the
      prescription plan when writing a prescription order will assure that the
      medication is provided efficiently, rather than having to deal with denials and
      an appeal process.

PMID- 16898057
TI  - The competitive acquisition program for drugs and biologicals.
AB  - Unlike the Medicare Part D program, which has a significant number of
      participating plans, the new Competitive Acquisition Program (CAP), which was to
      have started on Jan. 1, 2006, along with Medicare Part D, did not because, in
      part, of a lack of interest. As a result, the program was delayed until July 1,
      2006. This new program separates the physician from the purchase and billing of
      medications provided in the physician's office. Under CAP, physicians sign with a
      specialty pharmacy provider that will deliver the medications to the physicians
      as ordered and then bill Medicare directly. This will alleviate some physician
      administrative responsibilities. Although it is unlikely that high-volume
      Medicare Part B medication providers, such as oncologists, will use a CAP
      provider, it is likely that busy primary care physicians and other specialists
      not usually involved in providing medications in their offices now may start to
      take advantage of this valuable service.

PMID- 16898058
TI  - Medicare advantage: understanding special needs plans.
AB  - It has long been argued that managed care plans cherry picked members in an
      effort to encourage enrollment by healthy people who required fewer medical
      services. To prevent this practice, the federal government began to risk-adjust
      payments to managed care plans, based on the care needs of each member, thus
      removing any disincentives of enrolling sicker beneficiaries. The MMA gives plans
      the ability to focus on specific populations, so that services and systems can be
      tailored to those groups. Special Needs Plans (SNPs) can address 1 of 3 target
      populations: institutionalized beneficiaries, the dually eligibles, and
      beneficiaries with chronic or disabling conditions. By focusing on these groups,
      managed care plans can pull together unique systems of care to provide services
      in the most efficient and effective manner.

PMID- 16898059
TI  - Impact of Medicare Part D on long-term care.
AB  - Most residents of long-term-care facilities (LTCFs) have Medicare and are
      eligible to enroll in the Part D prescription drug benefit. Although nursing home
      residents face the same issues as other Medicare beneficiaries in choosing and
      enrolling in a prescription drug plan, they face additional challenges because of
      their health and the setting in which they live. They may have fewer drug plan
      choices, the pharmacies they use may not be included in the LTCF network, and
      their medication requirements vary considerably. This article presents the
      demographics of LTCFs, common disease states and medication consumption
      statistics among their residents, the effect of Medicare Part D, the relationship
      between LTCF pharmacies and prescription drug plans, and the special challenges
      associated with e-prescribing in long-term care.

PMID- 16898060
TI  - Can a moose inspire leadership?

PMID- 16898061
TI  - Guide to critical care ethics not ready for prime time.

PMID- 16898062
TI  - Proposal would limit profit of some California plans.

PMID- 16898063
TI  - Employers' stock in wellness rises with no end in sight.

PMID- 16898064
TI  - Banks give insurers an offer most of them cannot refuse.

PMID- 16898065
TI  - Oncologic PET study seeks basis for coverage decisions.

PMID- 16898066
TI  - Managed care prepares for the worst.

PMID- 16898067
TI  - High-tech imaging full of kickback dangers.

PMID- 16898068
TI  - Specialty anti-inflammatories see huge increase in utilization.

PMID- 16898070
TI  - Public payers foot greater pharmacy costs.

PMID- 16898069
TI  - Device allows doctors to see inside the small intestine.

PMID- 16898071
TI  - Penetration of ASM 981 in canine skin: a comparative study.
AB  - ASM 981 has been developed for topical treatment of inflammatory skin diseases.
      It specifically inhibits the production and release of pro-inflammatory
      cytokines. We measured the skin penetration of ASM 981 in canine skin and
      compared penetration in living and frozen skin. To make penetration of ASM 981
      visible in dog skin, tritium labelled ASM 981 was applied to a living dog and to
      defrosted skin of the same dog. Using qualitative autoradiography the radioactive
      molecules were detected in the lumen of the hair follicles until the
      infundibulum, around the superficial parts of the hair follicles and into a depth
      of the dermis of 200 to 500 microm. Activity could not be found in deeper parts
      of the hair follicles, the dermis or in the sebaceous glands. Penetration of ASM
      981 is low in canine skin and is only equally spread in the upper third of the
      dermis 24 hours after application. Penetration in frozen skin takes even longer
      than in living canine skin but shows the same distribution.

PMID- 16898072
TI  - Pharmacokinetics, tissue distribution and excretion of vinflunine.
AB  - The plasma pharmacokinetics, tissue distribution, excretion and binding to plasma
      proteins of vinflunine, were investigated after intravenous (iv) administration.
      We obtained plasma profiles after iv administration of vinflunine at the doses of
      3.5, 7 and 14 mg/kg in rats. The t1/2 values for vinflunine were estimated to be
      18.38+/-1.20, 17.05+/-0.77, 18.35+/-1.57 h, and the mean AUC0-t values were
      3.48+/-0.38, 6.54+/-0.68, 12.79+/-2.93 microg x h/ml, respectively. Of the
      various tissues tested, vinflunine was widely distributed into tissues, with the
      highest concentrations of vinflunine being found in well perfused organs. Maximal
      concentration of vinflunine was reached at 0.5 h postdose in the majority of
      tissues. In tumor-bearing mice, the similar pattern of tissue distribution was
      observable, except that vinflunine can be distributed into tumor. The binding of
      vinflunine in human and rat plasma proteins were 39.6% and 58.4% respectively.
      Within 96 h after administration, 9.58%, 15.36% and 0.71% of the given dose was
      excreted in urine, feces and bile, respectively. In conclusion, Vinflunine had a
      longer terminal half-life, a wide tissue distribution and less than 25% of the
      given dose was excreted as unchanged drug, suggesting metabolism as a major style
      of elimination.

PMID- 16898073
TI  - The pharmacokinetics of orally administered fudosteine in healthy Chinese
      volunteers.
AB  - The pharmacokinetics of fudosteine in healthy Chinese volunteers was investigated
      for the first time after single- and multiple-dose administration. Five male and
      five female volunteers were enrolled in this study. Each subject received 400 mg
      fudosteine capsules (the therapeutic dose) on day 1 after overnight fasting for
      the single-dose study and three times daily oral administration (400 mg) for 5
      consecutive days until the sixth morning for the multiple-dose study. Serial
      blood samples were collected at specified time intervals up to 16 hours following
      the first and last doses of fudosteine. Plasma harvested from the blood was
      separated and analyzed for fudosteine levels by a validated high-performance
      liquid chromatography-electrospray ionization mass spectrometry (HPLC/ESI/MS)
      method employing percolumn derivatization with 9-fluorenylmethyl chloroformate
      (FMOC-Cl). Noncompartmental analysis was used for the calculation of the total
      area under the plasma concentration-time curve (AUC) from time zero to time
      infinity and the terminal half-life (t1/2) of fudosteine. The pharmacokinetic
      parameters for single- and multiple-dose administration were estimated as
      follows: Cmax amounted to 10.13+/-4.39 microg/mL and 11.75+/-6.51 microg/mL, tmax
      to 0.69+/-0.36 h and 0.53+/-0.12 h and t1/2 to 2.33+/-0.63 h and 2.40+/-0.37 h,
      respectively. No significant differences were found between single- and multiple
      dose oral administration, although gender differences were observed.

PMID- 16898074
TI  - A bioequivalence study of levothyroxine tablets versus an oral levothyroxine
      solution in healthy volunteers.
AB  - Probably for genetic reasons a substantial part of the Greek population requires
      Levothyroxine treatment. Since commercially available Levothyroxine was first
      marketed, the manufacture and storage of the drug in tablet form has been
      complicated and difficult; and as cases of therapeutic failure have frequently
      been reported following treatment with this medicinal agent, quality control is
      an essential factor. Due to the unreliability of Levothyroxine-based commercial
      products, in the present study we decided to follow the Food and Drug
      Administration (FDA) guidelines*, and use a Levothyroxine solution as reference
      product. The bioavailability of the Levothyroxine sodium tablet formulation
      THYROHORMONE/Ni-The Ltd (0.2 mg/tab) and that of a reference oral solution (0.3
      mg/100 ml) under fasting conditions were compared in an open, randomized, single
      dose two-way crossover study. Twenty four healthy Caucasian volunteers (M/F=15/9,
      mean age=32.9+/-7.4yr) participated in the study. Bioavailability was assessed by
      pharmacokinetic parameters such as the area under plasma concentration-time curve
      from time zero up to the measurable last time point (AUC(last)) and the maximum
      plasma concentration (Cmax). Heparinized venous blood samples were collected pre
      dose and up to a 48-hour period post-dose. Levothyroxine sodium in plasma samples
      was assayed by a validated electrochemiluninescent immunoassay technique.
      Statistical analysis showed that the post-dose thyrotropin-stimulating hormone
      (TSH) levels decreased significantly (p<0.05). Regarding Levothyroxine (T4), the
      point estimate of the test formulation to the reference formulation ratios (T/R)
      for AUC(last) and Cmax was 0.92 with 90% confidence limits (0.90, 0.94) and 0.93
      with 90% confidence limits (0.91, 0.94), respectively. Regarding triiodo-L
      thyronine (T3), the point estimate for the T/R ratios of AUC(last) and Cmax was
      0.92 with 90% confidence limits (0.90, 0.95) and 0.94 with 90% confidence limits
      (0.92, 0.95), respectively. The 90% confidence limits for the pharmacokinetic
      parameters AUC(last) and Cmax lie within the acceptance limits for bioequivalence
      (0.80, 1.25), for both T3 and T4.

PMID- 16898075
TI  - Spline functions in convolutional modeling of verapamil bioavailability and
      bioequivalence. I: conceptual and numerical issues.
AB  - A cubic spline function for describing the verapamil concentration profile,
      resulting from the verapamil absorption input to be evaluated, has been used.
      With this method, the knots are taken to be the data points, which has the
      advantage of being computationally less complex. Because of its inherently low
      algorhythmic errors, the spline method is less distorted and more suitable for
      further data analysis than others. The method has been evaluated using simulated
      verapamil delayed release tablet concentration data containing various degrees of
      random noise. The accuracy of the method was determined by how well the estimates
      of input rate and extent represented the true values. It was found that the
      accuracy of the method was of the same order of magnitude as the noise level of
      the data. Spline functions in convolutional modeling of verapamil formulation
      bioavailability and bioequivalence, as shown in the numerical simulation
      investigation, are very powerful additional tools for assessing the quality of
      new verapamil formulations in order to ensure that they are of the same quality
      as already registered formulations of the drug. The development of such models
      provides the possibility to avoid additional or larger bioequivalence and/or
      clinical trials and to thus help shorten the investigation time and registration
      period.

PMID- 16898076
TI  - Spline functions in convolutional modeling of verapamil bioavailability and
      bioequivalence. II: study in healthy volunteers.
AB  - The pharmacokinetics of a new verapamil retard tablet formulation have been
      investigated in a randomized cross-over bioequivalence study on 12 healthy
      subjects. The drug was given orally at a single new or standard retard tablet
      dose of 240mg and at a single intravenous dose of 5mg. Plasma verapamil
      concentrations were determined by HPLC. New retard tablets produced peak plasma
      verapamil concentrations of 81.34+/-5.69microg/l, time to peak plasma
      concentrations of 4.91+/-0.89h and an AUC (0-24h) of 1291+/-103.4h x microg/l,
      with a terminal phase half-life of 55.1+/-14.9h. After intravenous administration
      verapamil exhibited biphasic elimination kinetics with a terminal plasma half
      life of 2.36+/-0.42h and systemic clearance of 34.32+/-5.81 l/h. Bioavailability
      of the new peroral retard formulation ranged from 19.49+/-4.41% to 67.69+/
      11.70%. Absorption rates and amounts were evaluated by means of the spline
      convolutional method. Input rates for the new verapamil retard formulation ranged
      from 0.77+/-0.20mg/h to 5.57+/-1.58mg/h. The cumulative amount of verapamil input
      was 39.17+/-9.71% for the new retard tablets. All pharmacokinetic parameters for
      the new verapamil retard tablet formulation, were in reasonable agreement with
      the data obtained on already registered verapamil retard formulations, indicating
      their bioequivalence.

PMID- 16898077
TI  - H3 Propranolol serum levels following lidocaine administration in rats with CCL4
      induced liver damage.
AB  - Liver disease alters the pharmacokinetic and pharmacodynamic properties of
      hepatically eliminated drugs. The main factors influenced are plasma albumin
      levels, enzyme balance (induction & inhibition) and drug binding to tissue
      proteins. The influence of lidocaine on serum, heart and liver propranolol levels
      in Wistar rats after liver injury induced by carbon tetrachloride CCl4 0.4 ml/kg
      x 2/wkl, was investigated. 40 male Wistar rats were divided into four groups (I,
      II, III, IV; n=10), Group I animals received only propranolol (labelled + cold
      substance) 40 mg/kg/12 h p.o., group II propranolol plus lidocaine in a single
      dose of 4mg/kg s.c., group III was treated with CCl4 for 6 weeks and received
      propranolol x2 at the same dosage as group I, while group VI was treated with
      CCl4 and the same drug dosage as group II. The simultaneous administration of H3
      propranolol and lidocaine increased propranolol levels in the serum and tissues.
      The liver in damaged animals showed an increase of propranolol level under
      lidocaine co-administration, probably due to CCl4 induced liver enzyme activity,
      resulting in a rapid propranolol metabolism or to competition between both drug
      protein binding sites. The increased propranolol levels in the heart after
      lidocaine administration were probably due to attributed to its high affinity for
      heart tissue. Consequently, as regards the therapeutic approach for patients with
      liver disease receiving propranolol their propranolol dosage should be reduced
      when lidocaine is co-administered.

PMID- 16898078
TI  - Formation of glucoside conjugate of acetaminophen by fungi separated from soil.
AB  - The phase II metabolite of acetaminophen in filamentous fungi and actinomycetes
      separated from soil was investigated. Fifty-four filamentous fungi and twenty
      seven actinomycetes were screened to transform acetaminophen. The metabolites of
      acetaminophen were assayed using liquid chromatography-tandem mass spectrometry.
      The only metabolite was subject to enzymatic hydrolysis to confirm its structure.
      Acetaminophen was converted into glucoside conjugate, by filamentous fungi JX1
      60, LN17-2, LN20-1 and the yield of the conjugate was 60.01%, 44.27%, 100%,
      respectively, and no phase I metabolites were detected. Glucoside conjugation of
      acetaminophen in filamentous fungi differs from the phase II metabolism of
      glucuronidation in humans. The fungus LN20-1 could be a suitable model to
      synthesize glucoside conjugate of acetaminophen.

PMID- 16898079
TI  - Pharmacokinetics of IL-18 binding protein in healthy volunteers and subjects with
      rheumatoid arthritis or plaque psoriasis.
AB  - IL-18 binding protein (BP) neutralizes the activity of IL-18, a cytokine
      implicated in psoriasis and rheumatoid arthritis (RA). We investigated the
      pharmacokinetics, pharmacodynamics and safety of recombinant human IL-18 BP (r
      hIL-18 BP) in healthy volunteers and subjects with psoriasis or RA in four phase
      I studies. A) Healthy volunteers (n = 24) were randomised to receive a single
      subcutaneous (sc) injection of r-hIL-18 BP (20, 70, 210 or 350 mg) or placebo. B)
      Healthy volunteers (n = 10) were randomised to receive six sc injections of r-hIL
      18 BP (35 or 175 mg, 48 h between injections) or placebo. C) Subjects with
      moderate-to-severe plaque psoriasis (n = 35) were randomised to receive r-hIL-18
      BP (20, 160 or 320 mg, sc tiw) or placebo for 6 weeks. D) Subjects with active,
      moderate-to-severe RA (n = 36) were randomised to receive r-hIL-18 BP (20, 80,
      160 mg, sc tiw) or placebo for 6 weeks. Pharmacokinetics, pharmacodynamics and
      safety were assessed in all four studies. r-hIL-18 BP showed a dose-dependent
      pharmacokinetic profile, with a peak serum concentration of 6-48 hours. With
      repeated sc injections tiw, a steady state was achieved in 1-2 weeks among
      subjects with psoriasis or RA. The majority of adverse events were mild or
      moderate in severity. Injection site reactions were the most frequently reported
      event in subjects with psoriasis or RA. r-hIL-18 BP displays dose-dependent
      pharmacokinetics, has a favourable safety profile and is well-tolerated in
      healthy volunteers and in subjects with moderate-to-severe plaque psoriasis or
      active, moderate-to-severe RA.

PMID- 16898080
TI  - Hepatobiliary transport of YM466, a novel factor Xa inhibitor, in rats.
AB  - YM466, a novel factor Xa inhibitor, is a hydrophilic compound with a carboxylic
      acid moiety. Previous studies in rats have shown that YM466 does nor undergo
      metabolism but is excreted into the bile and urine in unchanged form. Thus, in
      this study, we investigated in vivo hepatobiliary transport, focusing in
      particular on multidrug resistance-associated protein 2 (Mrp2/Abcc2)-mediated
      transport. The hepatobiliary transport of YM466 was investigated after its
      systemic infusion into Sprague-Dawley rats (SDRs) and Eisai hyperbilirubinemic
      rats (EHBRs), which lack Mrp2. When the binding of YM466 in the plasma and liver
      was examined, the bile-to-plasma concentration ratio and the liver-to-plasma
      concentration ratio for the unbound concentration in SDRs amounted to 32.2 and
      2.83, respectively, suggesting concentrated transport. The bile-to-liver
      concentration ratio for the unbound concentration in EHBRs was not lower than
      that found for SDRs. These findings suggest that YM466 is excreted from the
      plasma into the bile in a concentrated manner; however, Mrp2 does not play a
      major role in biliary excretion.

PMID- 16898081
TI  - Pharmacokinetics-pharmacodynamics of micafungin in Japanese patients with deep
      seated mycosis.
AB  - The objective of this study was to describe the pharmacokinetic profile and
      investigate the effective concentration of micafungin in Japanese male patients
      with deep-seated mycosis. 66 patients were treated with i.v. micafungin 12.5-150
      mg intravenously for up to 56 days. At this dose range, micafungin showed linear
      pharmacokinetics, and the mean values of Cmax and Cmin amounted to 3.16-12.9
      microg/mL and 0.70-3.68 microg/mL, respectively. The mean value for the
      elimination half-life was 13.5 h (95 samples from 65 patients), and it remained
      almost constant over the dose range. In addition, the elimination half-life was
      not influenced by age, gender or weight, and was similar to that found in healthy
      subjects. The active metabolites M1 and M2 were detectable, but their exposure
      was lower than that of the unchanged drug. The pharmacokinetic-pharmacodynamics
      ob micafungin were then investigated. The overall clinical response rate against
      aspergillosis and candidiasis showed good results at a dose of 50 mg and over.
      The Cmax and Cmin at the latter dose amounted to 5.16 and 1.41 microg/mL,
      respectively. In conclusion, micafungin showed linear pharmacokinetics at doses
      ranging from 12.5 to 150 mg, and the effective concentration was considered to be
      over 5 microg/mL as maximum level in Japanese patients with deep-seated mycosis
      such as candidiasis and aspergillosis.

PMID- 16898082
TI  - [The role of biologic agents in the therapy of ankylosing spondylitis].
AB  - Ankylosing spondylitis is a chronic, inflammatory rheumatic disease which
      etiology and pathogenesis are not yet fully understood. The inflammation involves
      the spine and also the peripheral joints might be affected in some cases
      resulting in a progressive ankylosis, restricted mobility, significant
      disability, loss of productivity and decreased quality of life. Gene technology
      based new drugs of the past decade, the biologic agents, offer an alternative
      opportunity for the treatment of ankylosing spondylitis in comparison with the
      previous drugs with doubtful efficiency. In Hungary infliximab and etanercept has
      been registered for ankylosing spondylitis. The aim of this study was to evaluate
      the efficacy of infliximab and etanercept by the available randomised controlled
      trials. A systematic search of the literature was performed from 01. 01. 2000 to
      08. 31. 2005. and the relevant publications were analysed following the concepts
      of evidence based medicine. 7 double blind, randomised, placebo controlled trials
      were identified, three for infliximab (n = 389) and four for etanercept (n =
      431). Although the inclusion criteria, the duration of the trials and the primary
      endpoints were different, the results confirm that both drugs significantly
      decrease symptoms and disease activity, and this effect is sustained during the
      therapy, nevertheless half of the patients did not achieve the standardised
      criteria of 50% decrease in disease activity. Both agents are well tolerated by
      patients. The outcomes of long-term therapy are reassuring by open extension
      studies of three years. Guidelines for biologic therapy has been developed in
      Hungary determining the target patient group, the conditions of the therapy and
      also an arthritis centre network has been established. Though individual
      admission is feasible, biologic drugs are not under reimbursement in Hungary.
      High drug costs makes the implementation of this new therapeutic opportunity
      difficult in the daily medical practice.

PMID- 16898083
TI  - [Antibiotic consumption between 1996 and 2003: national survey and international
      comparison].
AB  - AIMS: To describe the qualitative and quantitative changes of antibiotic
      consumption in Hungarian hospitals and in the primary care setting between 1996
      and 2003. METHODS: Sales data relating to community and hospital care antibiotic
      consumption were obtained for the 8 years period of 1996-2003. The 2003 version
      of the world health organisation (WHO) anatomical therapeutic chemical (ATC)/
      defined daily dose (DDD) system was used for calculations and the 2005 version
      for classifications. The final expression units were DDD/100 bed-days and
      DDD/1000 inhabitants/day for hospital and community care utilization,
      respectively. Trend analysis was applied to assess the annual changes in
      antimicrobial consumption. RESULTS: The total antibiotic consumption in the
      community setting and in the hospitals remained relatively stable during the
      study period. The average antibiotic consumption in the community setting (20.20
      +/- 1.42 DDD/1000 inhabitants/day was in line with the European average, while
      the national average hospital antibiotic consumption (24.81 +/- 1.69 DDD/ 100 bed
      days) was very low in international benchmark. Changes in the pattern of
      antibiotic consumption was observed in both settings. Internationally outstanding
      consumption of penicillins plus beta-lactamase inhibitor combinations (J01CR) and
      sulphonamides and extremely low utilisation of beta lactamase resistant
      penicillins (J01CF) were detected. The hospital antibiotic consumption was
      characterized by extended use of sulphonamides, tetracyclines, and second
      generation cephalosporins. CONCLUSIONS: The low hospital consumption of
      antibiotics and the internationally extreme usage of certain antibiotic groups
      needs further pharmacoepidemiologic analysis.

PMID- 16898084
TI  - [Diagnosis of diabetes mellitus].
AB  - Beside the clinical diagnosis of diabetes mellitus based on the measurement of
      blood glucose level, these days, the etiologic classification of the disease
      comes to the forefront. Genetic analysis (HLA typing, searching for glucokinase
      gene and mitochondrial gene mutations), immunologic examination (determination of
      islet specific autoantibodies) and measurement of the insulin secretory capacity
      help the etiologic classification. The most important result of classification is
      the discovery of the slowly progressive form of type 1 diabetes mellitus
      (formerly latent autoimmune diabetes in adults). Another direction of diagnostic
      procedures is the prediction of the disease in nondiabetic population. The
      prediction of type 1 diabetes is not specific enough at present, but that of type
      2 diabetes can be done easily.

PMID- 16898085
TI  - [The role of gallium scintigraphy in the diagnosis of sarcoidosis and in
      monitoring treatment effectiveness].
AB  - Sarcoidosis is an inflammatory disorder of unclear origin that can affect many
      organs. The hallmark of sarcoidosis is formation non-caseating epithelioid cell
      granulomas. The aetiology and the pathogenesis of the disease are not well
      understood, therefore in the absence of specific histopathology distinguishing
      marks the diagnosis is established by exclusion. In this case, the authors
      present a unique case of Boeck sarcoidosis with pulmonary manifestation and
      pleural involvement. They would like to draw attention to the importance of
      gallium scintigraphy in the diagnostic workup of the disease. During the
      diagnostic process, the exact diagnosis could be established with the help of
      gallium scintigraphy. Gallium scan also played an important role in identifying
      extrapulmonary manifestations. Serial control examinations--as being the only
      sensitive non invasive diagnostic test method- provided valuable help in
      estimating the activity of the inflammatory process and monitoring therapeutic
      efficacy.

PMID- 16898086
TI  - [An overview of the Hungarian-German relations in neuropathology].

PMID- 16898087
TI  - [Local history of a community from the viewpoint of public health].

PMID- 16898088
TI  - [Influence of computer tomography diagnostics on the treatment in state health
      care system].
AB  - The presented paper is a continuation of the widely debated topic on the role of
      radiation technologies, including computed tomography (CT), in municipal
      medicine, which has been earlier raised on the pages of the Vestnik. The main
      objective of the paper is that by using the results obtained from the use of CT
      in a near-Moscow health care facility that is typical of Russia's municipal
      health care service, the author attempted to provide evidence that it is
      necessary to extensively introduce this technique into the most mass link of
      Russian public health care--municipal medicine. As an evidence basis, the author
      analyzed changes occurring in the organization of a therapeutic-and-diagnostic
      process the municipal health care facility from a great variety of organ and
      system pathology that is particularly important from the practical point of view.
      The data obtained before and after introduction of CT into the municipal
      diagnostic algorithms on specific, the most critical clinical situations are
      compared. Moreover, objective analytical data are confirmed by a battery of
      brilliant diagnostic images. The author elucidates the readiness of municipal
      clinicians for virtually complete use of CT data for their purposes. By using
      several nosological entities, he shows the CT-induced transfer of some
      therapeutic procedures from the regional to municipal area of practice. In
      addition, arguments are advanced in favor of the thesis that some therapeutic
      technologies now in use are not up to world standards and municipal health care
      cannot be in compliance with civilized standards without its effective diagnostic
      support. Prominent in the paper is the description of changes in the continuity
      of diagnostic medicine at the municipal and regional levels after inclusion CT
      into the day-to-day activities of a municipal facility. It is concluded that the
      population needs for CT: one 24-slice unit per 50,000 dwellers of an area under
      service of a municipal facility.

PMID- 16898090
TI  - [Efficacy and safety of coronary stenting during diagnostic coronary angiography
      in patients with stable angina].
AB  - The authors assessed the in-hospital and long-term (up to 6 months) results of
      coronary stenting conducted just after diagnostic coronarography during a common
      procedure in patients with stable angina pectoris on effort. The 2001-2002 study
      included 2277 patients. The clinical indications for catheterization were
      Functional Classes II-IV stable angina on effort in 83 % of patients and silent
      ischemia in 17%. The study excluded patients with previous coronarography, acute
      coronary syndrome on admission, renal failure, left ventricular ejection fraction
      <30%, and left trunk stenosis. All the patients received aspirin and clopidogrel
      before catheterization. RESULTS: 57% of patients had multivessel disease; full
      revascularization was performed in 59% of the patients with multivessel disease.
      The coronary intervention was successful in 100% of cases. Significant in
      hospital events (myocardial infarction without Q wave) were in 1.2% of cases. The
      mean length of hospital stay was 2.9 +/- 2.4 days. The rate of stent thrombosis
      for as long as 30 days was 0.2%. Recurrent angina and/or positive exercise tests
      were in 12% during 6 months. CONCLUSION: immediate stening is effective and safe
      in most patients with stable angina during diagnostic catheterization. It does
      not increase immediate and late complications.

PMID- 16898091
TI  - [Estimation of cardiac output from dynamic contrast multispiral tomographic
      data].
AB  - OBJECTIVE: To describe and apply a method for programmatically calculating
      central hemodynamic parameters from the data of dynamic contrast X-ray computed
      tomography (CT). MATERIAL AND METHODS: A procedure is proposed to calculate
      cardiac output (CO) on the basis of the tracer dilution method as a ratio of the
      injected dose of a contrast agent (Urografin, Shering AG, Austria) to the area
      under the concentration-time curve derived for one of the cardiac chambers: [see
      text]. The blood concentration of the agent was estimated from the blood iodine
      (I) concentration-X-ray density (XD) regression dependence: [XD] = 0.49+22.07 x
      [I]. Thirty-three patients were studied on a multispiral X-ray Somatom Sensation
      4 computed tomograph (Siemens), by injecting 15-20 ml of Urografin. The
      calculating method was realized as a software package for processing dynamic
      contrast CT data. RESULTS: The proposed method could exactly determine the values
      of cardiac output: the correlation with the results of the reference technique
      (Doppler echo measurement) was highly significant (r = 0.95; p < 0.001) in the
      whole range of values. Moreover, the data on XD could accurately determine the
      blood concentration of both iodine (I): [XD] = 0.49+22.07 x [I] and gadolinium as
      a component of the contrast paramagnetic Gd-DTPA for which the solution
      concentration-XR dependence was as follows: XD 1.2+33.6 x [Gd]. CONCLUSIONS:
      Thus, dynamic spiral CT may be also used for the estimation of cardiac output by
      the tracer dilution method.

PMID- 16898089
TI  - [Comparative results of thyroid ultrasound and laboratory studies in patients
      exposed to radiation].
AB  - The paper presents the data of thyroid ultrasound and laboratory studies in 233
      persons exposed to radiation: 63 X-ray physicians, 36 Chernobyl accident
      liquidators, 31 patients with lymphogranulomatosis, receiving radiotherapy, and
      103 individuals (a control group) who were physicians of various specialties
      whose professional activity is unassociated with radiation factors. Thyroid
      changes were found in 67.7% of the examinees after gamma teletherapy and in 31%
      in the control group; among X-rat physicians and Chernobyl accident liquidators,
      the occurrence of thyroid changes was equal--44.4%. Direct radiation exposure of
      the thyroid in a dose of above 30 Gy led to the development of postradiation
      fibrosis (22.5%) and postradiation thyroiditis (32.3%) with thyroid dysfunction
      that is most commonly presented by hypothyroidism (22.45%). Autoimmune
      thyroiditis (11.1%) more predominantly with subclinical hypothyroidism, and
      diffuse thyroid hyperplasia (19.4%) resulted from mixed internal and external
      radiation. Thyroid changes revealed in X-ray physicians mainly appeared as
      nodular masses (22.2%) without functional impairments but to be followed up. It
      is recommended that the annual preventive examination protocol be supplemented by
      thyroid ultrasound studies in X-ray physicians.

PMID- 16898092
TI  - [Aseptic necrosis of the head of the femur in patients with major rheumatic
      diseases of inflammatory and dystrophic genesis].
AB  - A total of 2392 patients treated at the Unit of Rheumatology, Tula Regional
      Hospital, in 2002 and 2003 were analyzed. Among them, there were 71 patients who
      were found to have aseptic necrosis of the head of the femur. A statistical
      analysis of clinical, laboratory, and X-ray data revealed a number of
      correlations. It was established that the risk factors of aseptic necrosis of the
      femoral heads were anemia concurrent with the high laboratory values in
      rheumatoid arthritis and elevated lipid levels and blood coagulative system
      activation in primary coxarthrosis.

PMID- 16898093
TI  - [Technique of definition and diagnostic criteria of a state of blood flow of
      pelvis minor in woman with pelvis minor varicosis].
AB  - The aim of the research: the examination of the state of woven blood flow in
      women with pelvis minor varicosis. The study of woven blood flow by the method of
      radioisotope clearance in 72 women of reproductive age is carry ouied. In
      patients with the varicose expansion of the veins of pelvis minor was revealed
      significant reduction in the indices of blood flow in the organs of pelvis minor,
      which plays the leading part in the genesis of painful sidroma.

PMID- 16898094
TI  - [Magnetic resonance imaging (MRI) in the diagnosis of recurrences of ovarian
      cancer in the small pelvis].
AB  - The paper provides the results of small pelvic magnetic resonance tomography
      (MRI) in 62 patients with ovarian cancer after primary special treatment. Out of
      them 50 patients were found to have recurrences and metastases of the underlying
      disease, 12 patients had clinical remission. The study yielded MR signs and MR
      semiotics of recurrences of ovarian cancer in the small pelvis. The capacities of
      MRI with low and high intensities of a magnetic field were comparatively studied
      in the diagnosis of recurrences and metastases of ovarian cancer.

PMID- 16898095
TI  - [Evaluation of ultrasonography effectiveness in prostate cancer detection].
AB  - The database of examining 624 patients aged 49-85 were analyzed to define the
      diagnostic effectiveness of gray-scale, color and power Doppler transrectal
      ultrasonography (TRUS). Among them there are 473 (75.8%) cancer patients and 151
      (24.2%) benign prostate diseases patients. All the patients underwent a
      transrectal ultrasound examination with multifocal biopsy. The gray-scale, color
      and power Doppler transrectal ultrasound examination has the diagnostic accuracy
      of 75,3%. At this the effectiveness of the method increases with the Gleason sum
      growing.

PMID- 16898096
TI  - Managing CKD.
AB  - The reality is that the majority of the CKD population have one or more co-morbid
      conditions with a known higher prevalence in ethnic minorities and lower socio
      economic groups; combine this with the increase in childhood obesity and
      prevalence of diabetes and it is clear why we have an epidemic of CKD. Without
      effective prevention and early detection programmes, this will continue to
      escalate. Early detection and referral of CKD patients to nephrology teams is
      pivotal in slowing the progression to ESRD and reducing the demand for dialysis.

PMID- 16898097
TI  - Monitoring of dialysis water systems--is there a need for increased sampling?
AB  - Water quality is one of the most important aspects of ensuring a safe and
      effective delivery of haemodialysis. An extensive microbiological survey of
      several water systems highlighted a contamination problem which routine sampling
      had failed to detect. Current guidelines suggest that samples for microbiological
      and endotoxin analysis should be taken from the outlet of water treatment plant
      and points expected to have the highest bacterial load, normally the end of the
      distribution loop and connections to the dialysis machines, where the flow is at
      its lowest. The survey extended sampling to include a large number of machine
      connection points. Four systems were investigated. The samples from routine test
      points generally returned results within our operational limits (<10 CFU/ml and
      <0.06 IU/ml). However, results from several machine connection points exceeded
      these limits by a large margin. Several disinfection cycles were required in
      order to achieve results in keeping with our operational limits. The conclusion
      is that sample results from the end of the distribution loop may give a false
      sense of security by not indicating a contamination problem at the machine
      connection points. Increasing the number and frequency of machine connection
      points tested should provide greater security in detecting contamination and
      allow for remedial action at an earlier stage.

PMID- 16898098
TI  - Developing the European core curriculum in renal technology.
AB  - Working within the multi-professional team, renal technicians play a greater part
      in the functioning of renal units than in other less technical areas of care. The
      role of the renal technician has been changing and, is now one that often
      combines technical, scientific and clinical knowledge in utilizing technology so
      that the long-term outcomes of the patient are optimised and complications
      reduced. Therefore a sound knowledge base is vital in ensuring patients' safety.
      Whilst still centered on the traditional engineering functions such as equipment
      repair and maintenance, the curriculum is structured to give a broad overview of
      renal related physiology, chemistry, treatment modalities and technology. The
      inclusion of these more clinical aspects in the curriculum reflects the change in
      the technician's role to a more science-based approach.

PMID- 16898099
TI  - Meaning of illness and illness representations, crucial factors to integral care.
AB  - INTRODUCTION: A comprehensive study of end-stage renal disease (ESRD) and
      haemodialysis (HD) must include the sociocultural dimension of illness and the
      experience of patients from their own perspective. It is critical for the caring
      team to know how the disease is lived and reinterpreted by the patient, as this
      knowledge could improve nursing staff/patient interaction. The meaning of their
      experience is also an influential factor on the caring methods utilised by the
      patient. FRAMEWORK: The Theory of Representations and Explanatory Model of
      Illness was utilised in the study. METHODOLOGY: A narrative qualitative
      methodology, grounded in a constructivist paradigm was used. Twelve patients were
      interviewed. The interviews were audio taped and transcribed verbatim. RESULTS:
      Results revealed that patients have a range of beliefs about their illness and
      their treatment. Regarding identity, symptoms that arise at the outset of illness
      are not suspected of relating to renal failure. The inevitability of
      haemodialysis convinces patients of the presence of illness, opening a wide range
      of metaphors and symbolic representations. CONCLUSIONS: Representations of ESRD
      and HD conform to a multidimensional corpus where different elements of
      scientific order and common sense converge and interact, such as beliefs and
      fears. All of these contribute to the meaning of this illness and its treatment.
      The attributed meaning is dynamic being continually elaborated based on illness
      outcomes, adaptation to treatment, particular events and the sociocultural
      environment.

PMID- 16898100
TI  - The effect of progressive muscle relaxation training on anxiety levels and
      quality of life in dialysis patients.
AB  - AIM: To determine the effect of progressive muscle relaxation training (PMRT) on
      anxiety levels and quality of life (QoL) in dialysis patients. METHODS: A total
      of 46 patients who had been treated with dialysis in the Dialysis Center of Ege
      University Medical Faculty Hospital were recruited. Data were collected by means
      of a questionnaire. Patients' Recognition Form (PRF), State and Trait Anxiety
      Inventory (STAI), and QoL-index for dialysis patients (QoLI-dialysis) were used
      to collect the necessary data. All three forms were utilised prior to PMRT and 6
      weeks after completion of PMRT. RESULTS: The mean state-anxiety score before and
      after PMRT was found as 43.4 +/- 4.3 and 28.9 +/- 2.8, respectively (P<0.001).
      Similarly, the mean trait-anxiety scores before and after PMRT were found as 43.6
      +/- 9.5 and 31.1 +/- 6.5, respectively (P<0.001). When the QoLI-dialysis score
      was examined it was 28.7 +/- 3.2 before PMRT and 29.6 +/- 2.3 after PMRT
      (P<0.01). CONCLUSION: The results of the study demonstrate that PMRT for dialysis
      patients helps decrease state- and trait-anxiety levels and has a positive impact
      on QoL.

PMID- 16898101
TI  - Caring for people who are dying on renal wards: a retrospective study.
AB  - Unfortunately, there is still a high mortality rate among patients with end-stage
      renal disease (ESRD). If the decision is made to activate non-dialytic management
      of the patient with ESRD, it should be made jointly by the patient and
      responsible consultant nephrologist after consultation with relatives, the family
      doctor and other relevant members of the caring team. This paper discusses the
      establishment of a new renal supportive care service for patients opting not to
      have dialysis and focuses on the results of a 'death audit' carried out on this
      patient population. Recommendations for practice resulting from analysis of the
      audit results include, the use of advance directives, identification and prompt
      treatment of symptoms, increased staff education, timely referral to the
      palliative care team and expansion and further integration of the renal
      supportive care team.

PMID- 16898102
TI  - Symptom management in patients with established renal failure managed without
      dialysis.
AB  - Increasing numbers of patients with chronic kidney disease Stage 5 (GFR
      <15ml/minute) are being managed without dialysis, either through their own
      preference or because dialysis is unlikely to benefit them. This growing group of
      patients has extensive health care needs. Their overall symptom burden is high,
      and symptom prevalence matches or exceeds that in other end of life populations,
      both with cancer and other non-cancer diagnoses. These symptoms may often go
      unrecognised and under-treated. Regular symptom assessment is necessary, together
      with pro-active management of identified symptoms. Pain can be managed using the
      principles of the World Health Organisation analgesic ladder. Not all opioid
      medications are recommended for these patients. Paracetamol, tramadol, and
      fentanyl are the most appropriate medications for steps 1, 2 and 3 respectively.
      There is limited evidence on the use of buprenorphine, oxycodone and
      hydromorphone. Methadone is safe but should only be prescribed by a clinician
      experienced in its use. Morphine and diamorphine are not recommended because of
      metabolite accumulation. Pruritus is also challenging to manage. The evidence for
      pharmacological interventions to alleviate pruritus is summarized, and a
      pragmatic approach to management suggested. Emollients, capsaisin cream,
      antihistamines, thalidomide and ondansetron may be helpful, according to the
      extent and pattern of pruritus. Symptoms may frequently be due to co-morbid
      conditions, not renal disease itself, and managing them is difficult because of
      the constraints on the use of medication which kidney failure imposes.
      Collaboration between renal and palliative specialists can help identify ways to
      achieve best care for these patients.

PMID- 16898103
TI  - Dialysis: prolonging life or prolonging dying? Ethical, legal and professional
      considerations for end of life decision making.
AB  - There are over 7,000 people on dialysis in Australia and this is predicted to
      increase due to the ageing population and the high incidence of diabetes
      mellitus. Discontinuation of dialysis is the second most frequent cause of death
      in dialysis patients in Australia. Risk factors for the discontinuation of
      dialysis include: co-morbidities (especially diabetes mellitus) and being older.
      Because the decision to discontinue dialysis is a major life choice,
      collaborative decision making should be encouraged, and the patient needs
      assurances of the continuation of care and kindness, a palliative care plan, and
      the alleviation of suffering. Patients decide to discontinue dialysis because of
      an unacceptable quality of life, depression and a chronic failure to thrive.
      Health professionals need to support end of life decision making using an ethical
      decision framework. A review of current literature was undertaken and revealed a
      paucity of information in regard to palliation in those with end stage renal
      disease who had discontinued dialysis. The fear of dying, pain, suffering, and
      abandonment that a patient and/or their family may perceive as being associated
      with death may create barriers to decisions to discontinue with dialysis
      treatments. Therefore health care personnel should provide information with
      honesty to allow patients to predict their quality of life and death. Support for
      the patient and family during the dying period should be multi-disciplinary, with
      clear and timely communication between all members of the team.

PMID- 16898104
TI  - Earthquake in Pakistan--The Renal Disaster Relief Task Force in action.
AB  - Following an earthquake, an International stream of help is launched. Teams of
      nephrologists, renal nurses and technicians from many European countries are
      ready as volunteers to come into action when needed. Basic help is necessary but
      what is the benefit of nephrologists and renal nurses, as the Renal Disaster
      Relief Task Force comes into action? The scouting team assesses the situation in
      the disaster area. Treatment of acute renal failure, hyperkalemia and Crush
      Syndrome can be life saving. The ability to accommodate dialysis treatment is
      investigated, in collaboration with local nephrologists. Belgian, French, Irish
      and Turkish colleagues who made up two teams, with Medecins sans Frontieres (MsF)
      left for Pakistan following the devastating earthquake in October 2005. This is a
      report from one of the volunteers from the first team explaining the individual
      contribution that his mission made to the disaster.

PMID- 16898106
TI  - Why clown-doctors are needed in paediatric wards.

PMID- 16898105
TI  - Merits and limitations of continuous blood volume monitoring during
      haemodialysis. Summary of the EDTNA/ERCA Journal Club discussion: Winter 2005.
AB  - The discussion explored and expanded on the issues raised by Dasselaar et al in
      their review of the measurement of relative blood volume (RBV) changes during
      dialysis (NDT 2005). Dialysis machines incorporating blood volume monitoring and
      control are widely available in Europe. The use of continuous blood volume
      monitoring (CBVM) to help establish dry weight; problems with CBVM due to
      connection and use of single needle dialysis; the physiological processes that
      cause RBV changes during eating, exercise and posture changes; and the
      application of blood volume based biofeedback control were discussed by
      participants from ten countries. The 'take-home' messages from the discussion
      were that CBVM can assist in setting target weight, but must be used together
      with traditional measures and experience. Biofeedback control may help to achieve
      symptom-free dialysis, but staff should be prepared to monitor patients
      systematically for several weeks to obtain individualised settings. Users of CBVM
      should be aware of factors that can alter the central haematocrit leading to
      apparent changes in RBV. Practical guidelines should be developed to help staff
      interpret CBVM data effectively.

PMID- 16898107
TI  - Change we must.

PMID- 16898108
TI  - An ethicist's commentary on the woman walking the arthritic dog.

PMID- 16898109
TI  - Pilot study to evaluate 3 hygiene protocols on the reduction of bacterial load on
      the hands of veterinary staff performing routine equine physical examinations.
AB  - Reduction factors (RFs) for bacterial counts on examiners' hands were compared
      when performing a standardized equine physical examination, followed by the use
      of one of 3 hand-hygiene protocols (washing with soap, ethanol gel application,
      and chlorohexidine-ethanol application). The mean RFs were 1.29 log10 and 1.44
      log10 at 2 study sites for the alcohol-gel (62% ethyl alcohol active ingredient)
      protocols and 1.47 log10 and 1.94 log10 at 2 study sites for the chlorhexidine
      alcohol (61% ethyl alcohol plus 1% chlorhexidine active ingredients) protocols,
      respectively. The RFs were significantly different (P < 0.0001) between the hand
      washing group and the other 2 treatment groups (the alcohol-gel and the
      chlorhexidine-alcohol lotion). The use of alcohol-based gels or chlorhexidine
      alcohol hand hygiene protocols must still be proven effective in equine practice
      settings, but in this study, these protocols were equivalent or superior to hand
      washing for reduction in bacterial load on the hands of people after they perform
      routine physical examinations.

PMID- 16898110
TI  - Porcupine quill injuries in dogs: a retrospective of 296 cases (1998-2002).
AB  - The purpose of this retrospective study was to identify factors associated with
      quill injury in dogs. A second objective was to determine the risk of
      complications and any factors that would predict the likelihood of complications.
      Hospital records of 296 porcupine quill injuries in dogs from 1998 to 2002 were
      studied. There was an increased occurrence of porcupine encounters in the spring
      and fall months; Siberian huskies, rottweilers, and German shepherd crosses were
      significantly overrepresented for quill injuries. There was no association
      between risk of complications and either number of quills or antimicrobial use.
      Increasing time between quill injury and presentation was associated with an
      increased risk of complications. Because of the increased frequency of
      complication with a longer interval until presentation, clients should be
      strongly encouraged to bring the dog in as soon as the quill injury is
      discovered. Patients presented after 24 hours should be monitored closely during
      the first 3 weeks after injury, as most complications occurred during this time.

PMID- 16898111
TI  - Fatal sand impaction of the spiral colon in a 1-month-old alpaca.
AB  - A 1-month-old cria (Lama pacos) was presented because of depression, anorexia,
      and diarrhea for 3 days. Although treated for enteritis (intravenous fluids and
      antibiotics), the cria's condition deteriorated. An abdominal radiograph revealed
      radiodense materials in the 3rd compartment and intestines. The cria died due to
      sand impaction of the spiral colon.

PMID- 16898112
TI  - Treatment of presumptive idiopathic immune-mediated anemia in a Holstein heifer,
      using blood transfusions and corticotherapy.
AB  - An idiopathic immune-mediated anemia was diagnosed in a 1-year-old Holstein
      heifer. The diagnostic procedures, blood transfusions, use of an
      immunosuppressive dosage of dexamethasone, and favorable outcome are described,
      and idiopathic immune-mediated anemia in mammals is briefly reviewed.

PMID- 16898113
TI  - Diagnostic and epidemiological features of Lawsonia intracellularis enteropathy
      in 2 foals.
AB  - Two clinical cases of equine proliferative enteropathy are described. Both foals
      had a positive fecal polymerase chain reaction, but shedding of the bacterium
      stopped <4 days after therapy was initiated. One foal was serologically positive
      3 days after onset of clinical signs and remained positive for more than 6
      months.

PMID- 16898114
TI  - Prevalence of antibodies to serotypes of Bluetongue virus and Anaplasma marginale
      in Montana feeder cattle: 2002-2003.
AB  - In a serologic survey of Montana-source weaned calves and yearling cattle, the
      apparent prevalence of antibodies to Bluetongue virus was 0.68% and 1.26% in 2002
      and 2003, respectively, and to Anaplasma marginale at a positive cutoff at 30%
      inhibition it was 1.82% and 1.35% in 2002 and 2003, and at a positive cutoff at
      42% inhibition it was 0.76% and 0.55% in 2002 and 2003, respectively, suggesting
      that the risk of importing infected animals was very low.

PMID- 16898115
TI  - Acquired extrahepatic portosystemic shunts in a young dog.
AB  - A young, male miniature poodle was presented with severe neurological problems.
      Laboratory tests and ultrasonograph examination were consistent with extrahepatic
      portosystemic shunts, resulting in hepatic encephalopathy. When surgical
      correction proved not to be a viable option, the dog was euthanized. Postmortem
      examination revealed multiple shunts likely acquired after severe hepatitis.

PMID- 16898116
TI  - Veterinary practice manager le gestionnaire veterinaire.

PMID- 16898117
TI  - Palliative radiation therapy for canine osteosarcoma.

PMID- 16898118
TI  - Clinical pharmacology update. Insulin.

PMID- 16898119
TI  - The ethics of referral.

PMID- 16898120
TI  - Diagnostic ophthalmology ophtalmologie diagnostique.

PMID- 16898121
TI  - Virulent and attenuated lines of Leishmania major: DNA karyotypes and differences
      in metalloproteinase GP63.
AB  - The Leishmania metalloproteinase GP63 has been reported to play important roles
      mainly in resistance of promastigotes to complement-mediated lysis and in
      interaction with macrophage receptors. On the other hand, its function in insect
      vectors is still unclear. We compared the structure and dosage of gp63 genes and
      the activity of GP63 in Leishmania major Yakimoff et Schokhor strains and lines
      differing in virulence for mice and ability to develop in sand flies. The results
      demonstrate considerable variability in amount and proteolytical activity of GP63
      among L. major strains although genomic changes in the gp63 locus were not found.
      Attenuated LV561/AV line showed low amount and low enzymatic activity of GP63.
      Serial passages of attenuated parasites through either Phlebotomus duboscqi Neveu
      Lemaire or through mice led to a recovery of GP63 proteolytical activity to the
      level present in virulent LV561/V line. Overexpression of GP63 was found in two L
      major strains (L119, Neal) with defective lipophosphoglycan (LPG); both these
      strains were capable to cause mice infection but unable to survive and multiply
      in sand flies. Differences were found also in karyotypes and in amount of
      minichromosomes amplified in some lines of the LV561 strain. The results suggest
      that parasite virulence is not simply correlated with the activity of GP63;
      however, this enzyme plays a significant role in association with other surface
      molecules, especially LPG. Overexpression of GP63 can compensate LPG defect in
      the vertebrate host but in sand flies both molecules fulfil quite different
      functions and the defect in LPG is lethal for the parasite. On the other hand,
      linear minichromosomes of about 200 kb found in some lines of the LV561 strain
      are associated with development in vitro and in the vector but they are not
      essential for the infection of the vertebrate host.

PMID- 16898122
TI  - New species of Choleoeimeria (Apicomplexa: Eimeriidae) from the veiled chameleon,
      Chamaeleo calyptratus (Sauria: Chamaeleonidae), with taxonomic revision of
      eimerian coccidia from chameleons.
AB  - Coprological examination of 71 samples from a breeding colony of veiled
      chameleons, Chamaeleo calyptratus Dumeril et Dumeril, 1851, revealed a presence
      of two species of coccidia. In 100% of the samples examined, oocysts of Isospora
      jaracimrmani Modry et Koudela, 1995 were detected. A new coccidian species,
      Choleoeimeria hirbayah sp. n., was discovered in 32.4% of samples from the
      colony. Its oocysts are tetrasporocystic, cylindrical, 28.3 (25-30) x 14.8 (13.5
      17.5) microm, with smooth, bilayered, -1 microm thick wall. Sporocysts are
      dizoic, ovoidal to ellipsoidal, 10.1 (9-11) x 6.9 (6-7.5) microm, sporocyst wall
      is composed of two plates joined by a meridional suture. Endogenous development
      is confined to the epithelium of the gall bladder, with infected cells being
      typically displaced from the epithelium layer towards lumen. A taxonomic revision
      of tetrasporocystic coccidia in the Chamaeleonidae is provided.

PMID- 16898124
TI  - Revision and phylogeny of rhamnocercinae monaco, Wood et Mizelle, 1954
      (Monogenoidea: Diplectanidae).
AB  - Species of Rhamnocercinae Monaco, Wood et Mizelle, 1954 are gill parasites of
      sciaenid fishes (Perciformes). Seven are marine species (three in the western
      Atlantic and four in oriental Pacific) and one is a neotropical freshwater
      species (Rio Doce Basin, Brazil). While the status of the subfamily may be
      questioned, this assemblage of species is apparently supported by several shared
      apomorphic and plesiomorphic characters, such as: (1) peduncular spines with
      anterior and posterior roots; (2) haptor laterally expanded, armed with anchors
      (two pairs); bars (one ventral, two dorsal); 14 hooks and haptoral accessory
      spines; and (3) double (nested) tubes of the male copulatory organ (MCO),
      directed posteriorly with the genital pore lying posterior to the MCO. The
      phylogenetic hypothesis for the eight known species of this clade is:
      (Spinomatrix penteormos (Rhamnocercoides stichospinus, Rhamnocercoides
      menticirrhi) Rhamnocercus oliveri (Rhamnocercus rhamnocercus (Rhamnocercus
      stelliferi, Rhamnocercus bairdiella, Rhamnocercus margaritae)). This hypothesis
      indicates that Spinomatrix penteormos represents the sister group of all
      remaining rhamnocercines. The resulting phylogenetic sister-group relationships
      support the transfer of Rhamnocercus stichospinus Seamster et Wood, 1956 to
      Rhamnocercoides Luque et Iannacone, 1991 as Rhamnocercoides stichospinus
      (Seamster et Wood, 1956) n. comb.

PMID- 16898123
TI  - Temporal and spatial distribution of glochidial larval stages of European unionid
      mussels (Mollusca: Unionidae) on host fishes.
AB  - Glochidia are the larval stage of freshwater unionid mussels that parasitize the
      fins and gill apparatus of fish. A total of 22 fish species were examined for the
      presence of glochidia whose distribution on individual hosts was studied on three
      common fish species, the roach Rutilus rutilus (L.), perch Percafluviatilis L.
      and bitterling Rhodeus sericeus (Pallas). Between 1997 and 1999, the fish were
      obtained from the rivers Morava and Kyjovka and surrounding water pools in the
      Czech Republic. The glochidia of two genera, Unio and Anodonta, were found.
      Anodonta glochidia were observed on 10 fish species, Unio glochidia on 17 fish
      species. There was a difference in spatial distribution of glochidia on the body
      of the host fish. Unio glochidia were predominantly located on the gills, whereas
      most Anodonta glochidia were found on the fins, with the highest numbers of
      glochidia were observed on the margin of the pectoral fins. For the gill
      apparatus, Unio glochidia were found predominantly on the second and third arch.
      Anodonta glochidia were predominantly found during winter and spring (November
      May), whereas Unio glochidia were more abundant during May and June. The number
      of glochidia was positively correlated with fish length in perch highly infected
      by Anodonta glochidia and perch infected by Unio glochidia. Of the three fish
      species, the highest occurrence of parasites was found on perch with fewer
      observed on roach. In spite of the close relationship between bitterling and
      unionid mussels, glochidiosis was rare on this fish species.

PMID- 16898125
TI  - Psettarium anthicum sp. n. (Digenea: Sanguinicolidae) from the heart of cobia
      Rachycentron canadum (Rachycentridae) in the northern Gulf of Mexico.
AB  - Psettarium anthicum sp. n. (Digenea: Sanguinicolidae) infects the myocardium and
      atrial wall of the cobia Rachycentron canadum (Linnaeus, 1766) (Rachycentridae)
      in the northern Gulf of Mexico off Mississippi, USA. It is the first member of
      Psettarium Goto et Ozaki, 1930 reported from other than the Indian Ocean or
      Pacific Ocean and the second species of the genus reported from cobia. It differs
      from its congeners by the combination of having posterior caeca with lateral
      projections appearing as thorns in lateral view and the male pore anterior to the
      ootype. The species of Psettarium, P. japonicum (Goto et Ozaki, 1929) (type
      species), P. tropicum Manter, 1940, P. sebastodorum Holmes, 1971, P. rachycentri
      (Lebedev et Parukhin, 1972) comb. n. (syn. Psettarioides rachycentri Lebedev et
      Parukhin, 1972) and P. anthicum sp. n., differ from other sanguinicolids by the
      combination of having an elongate body with a sinistral posterolateral
      protuberance, minute, straight tegumental body spines in ventrolateral transverse
      rows, posterior caeca greater than seven time the anterior caeca length, the
      o6type near the posterior end of the body, a uterus primarily between the ovary
      and ootype and an oviduct and vitelline duct extending posteriad primarily
      between the uterus and dextral body margin. We emend Psettarium and provide a
      diagnostic key to the species. Psettarioides is regarded as a junior synonym of
      Psettarium because herein we return its type species, P. tropicum, to Psettarium.
      Regarding the three other sanguinicolids formerly of Psettarioides, we suspect
      that P. pseudupenei Lebedev et Parukhin, 1972 belongs to Psettarium but include
      it only tentatively pending an examination of type or other material; we
      tentatively place P. kurochkini Parukhin, 1976 in Cardicola Short, 1952; and we
      designate P. grandis (Lebedev et Mamaev, 1968) as incertae sedis pending
      examination of type or other appropriate material.

PMID- 16898126
TI  - Ophiotaenia bonneti sp. n. (Eucestoda: Proteocephalidea), a parasite of Rana
      vaillanti (Anura: Ranidae) in Costa Rica.
AB  - Ophiotaenia bonneti sp. n. is described from the intestine of the frog Rana
      vaillanti Brocchi, 1877 (Anura: Ranidae) from San Gerardo, Guanacaste, Costa
      Rica. The new species is characterized by the testes 100-177 in number, the
      genital pores situated anteriorly, the osmoregulatory canals overlapping the
      testis field, the cirrus pouch length as 15-24% of proglottis width, and the
      uterus with 18-32 ramified diverticula on each side. It differs from the 23 known
      species of the genus Ophiotaenia La Rue, 1911, parasitic in amphibians, by one to
      several morphological characters. It differs from O. gracilis Jones, Cheng et
      Gillespie, 1958, the most morphologically similar species, in the sucker diameter
      in % of scolex diameter and in the morphology of the eggs - funnel-like
      depression and embryophore closely investing the oncosphere in O. gracilis. We
      generally observe a very low mean prevalence of the Proteocephalidea in
      Neotropical amphibians (about 0.41%-3%), but in the case of some host species,
      the prevalence can reach up to 25%. We conclude that these cestodes exhibit a
      strict host specificity of the oioxene type. Ophiotaenia junglensis Srivastava et
      Capoor, 1980 is considered a species inquirenda. Batrachotaenia hernandezi
      (Flores-Barroeta, 1955) becomes Ophiotaenia hernandezi (Flores-Barroeta, 1955)
      comb. n., B. tigrina (Woodland, 1925) becomes O. tigrina (Woodland, 1925) comb.
      n. and B. ceratophryos (Parodi et Widakowich, 1916) becomes O. ceratophryos
      (Parodi et Widakowich, 1916) comb. n.

PMID- 16898127
TI  - Pseudodelphis limnicola sp. n. (Dracunculoidea: Guyanemidae) from the heart of
      Percichthys trucha (Perciformes: Percichthyidae) in Patagonian Andean Lakes
      (Argentina).
AB  - During a survey of parasites of Percichthys trucha (Cuvier et Valenciennes)
      (Perciformes: Percichthyidae) in northwestern Patagonian lakes, a new
      dracunculoid of the family Guyanemidae was found parasitizing as adults the heart
      of the fish. This species belongs to the genus Pseudodelphis Adamson et Roth,
      1990 by having deirids, glandular multinucleate oesophagus and anterior branch of
      the uterus, and by lacking caudal alae and a gubernaculum. Pseudodelphis
      limnicola sp. n. differs from Pseudodelphis oligocotti Adamson et Roth, 1990 by
      the number and distribution of the cephalic papillae, a muscular oesophagus
      submerged into the glandular portion and by lacking a peribuccal ring. This is
      the first record of a guyanemid inhabiting the heart of a Neotropical perciform
      fish.

PMID- 16898128
TI  - Two new species of philometrid nematodes (Nematoda: Philometridae) from the
      southern flounder Paralichthys lethostigma in the estuaries of South Carolina,
      USA.
AB  - Two new philometrid nematodes, Philometra overstreeti sp. n. and Philometroides
      paralichthydis sp. n., are described from female specimens collected from the
      southern flounder Paralichthys lethostigma Jordan et Gilbert (Paralichthyidae,
      Pleuronectiformes) in estuaries of South Carolina, USA. P. overstreeti is
      characterized by the presence of eight large, equal in size cephalic papillae,
      the absence of caudal projections, the body length of gravid females (14.10-27.06
      mm) and the location in the host (among teeth). P. paralichthydis from the host's
      fins and the buccal cavity differs from its congeners mainly in possessing
      longitudinal cuticular ornamentations in addition to transverse ones or
      individual rounded bosses. It is the first species of Philometroides reported
      from flatfishes (Pleuronectiformes). A re-examination of type specimens of
      Margolisianum bulbosum Blaylock et Overstreet, 1999 showed that, in fact,
      nematodes belonging to two different species (now described to be new to science)
      and genera were confused in the original description of this taxon and in the
      diagnosis of Margolisianum. Since the male holotype of M. bulbosum cannot be
      identified to genus, Margolisianum bulbosum is a species inquirenda and a species
      incertae sedis. Consequently, Margolisianum becomes a genus inquirendus.

PMID- 16898129
TI  - Relationships between the parasitic mite Spinturnix andegavinus (Acari:
      Spinturnicidae) and its bat host, Myotis daubentonii (Chiroptera:
      Vespertilionidae): seasonal, sex- and age-related variation in infestation and
      possible impact of the parasite on the host condition and roosting behaviour.
AB  - Host-parasite relationships between the Daubenton's bat, Myotis daubentonii Kuhl,
      1817 (Chiroptera: Vespertilionidae), and its haematophagous ectoparasite, the
      mite Spinturnix andegavinus Kolenati, 1857 (Acari: Spintumicidae), were subjected
      to analyses based on data gathered during a six-year study (1999-2004) within a
      single study area in South Bohemia, Czech Republic. Seven hundred and fifty-one
      Daubenton's bats were examined by screening wing membranes with an intensive
      light source, resulting in 4,690 recorded mites. Sex, age, weight and
      reproductive state were evaluated for each bat. A body condition index was
      calculated as a ratio of weight to forearm length. The seasonal course of mite
      infestation displayed distinct dynamics with the peak during the lactation and
      post-lactation periods coinciding with occurrence of the most numerous colonies
      of Daubenton's bats in the study area. Infestation rates differed between the two
      sexes, being higher in adult females than adult males. Juvenile bats of both
      sexes (with no differences between males and females) were the most infested
      group of all. Pregnant females had a significantly higher parasite load than non
      pregnant ones, while no differences in infestation rates were found between
      lactating and non-lactating females. The analyses of the relationship between
      parasite load and body condition of bats revealed no common trends for all sex-
      and age-related groups. Two possible explanations are suggested and discussed:
      (1) There is no true relationship between the two tested variables and, thus, the
      significant results were attained due to a random statistical effect. (2)
      Different underlying causal mechanisms may exist that influence parasite load
      and, especially, body condition, with respect to the particular sex and age
      category of bats. The seasonal roosting dynamics of the Daubenton's bat are
      suggested to be the result not only of changing energetic demands of resident
      population members, but also of coevolutionary strategies within host-parasite
      relationships.

PMID- 16898130
TI  - Effect of salivary gland extract from Ixodes ricinus ticks on the proliferation
      of Borrelia burgdorferi sensu stricto in vivo.
AB  - Saliva-activated transmission (SAT) of Borrelia burgdorferi sensu stricto was
      demonstrated using real-time PCR and salivary gland extract (SGE) from partially
      fed Ixodes ricinus ticks. C3H/HeN mice were injected intradermally with 1.5 x
      10(3) spirochetes mixed with 40 microg of SGE per mouse. The control group was
      inoculated with the same dose of spirochetes without SGE. The accelerating effect
      of SGE on spirochete proliferation was demonstrated on day 1 post infection, when
      a 4.2-fold increase in spirochetes was found in the skin and a 10-fold increase
      in the blood, compared with control mice. The data represent the first direct
      evidence of a SAT effect of I. ricinus SGE on infection with the Lyme disease
      agent B. burgdorferi.

PMID- 16898131
TI  - Measurement and modelling of ordinary heterotrophic organism active biomass
      concentrations in anoxic/aerobic activated sludge mixed liquor.
AB  - Ordinary heterotrophic organism (OHO) active biomass (ZBH) is a key parameter in
      models for activated sludge systems, which defines quantitatively the kinetic
      rates of relevant processes. However, ZBH has not been measured directly with
      consistent success: a simple respirometric batch test has provided varying
      correspondence between measured and theoretical concentrations. In this paper,
      the batch test is applied to mixed liquors drawn from well defined anoxic/aerobic
      parent systems at 10 and 20 d sludge ages, with consistent but poor
      correspondence between measured and theoretical values. In contrast, aerobic
      digestion batch tests on the same mixed liquors give good correspondences. It is
      concluded that the differences between theoretical and batch test measured values
      are due to the batch test method itself and its interpretation. It is found that
      the batch test conditions (particularly the substrate/ZBH ratio) influence the
      kinetic constants derived from the data, and hence the ZBH estimate. Two kinetic
      models with two competing OHO populations, a fast and a slow grower, are
      developed and applied to the batch tests and parent systems. The first model is
      based on kinetic selection only, while the second includes additional metabolic
      selection. Both models can account for the observations in the batch tests, but
      the second provides greater consistency between simulations of the parent systems
      and batch tests.

PMID- 16898132
TI  - An evaluation of full-scale activated sludge dynamics using microbial fatty acid
      analysis.
AB  - Patterns of microbial fatty acids (MFAs) from activated sludge samples were
      analyzed over one year's operation at the Hamilton Woodward municipal wastewater
      treatment plant in Canada. The objective was to examine community structure
      dynamics and to consider the potential for interrelationships between the
      population dynamics and treatment performance. With the exception of a higher
      than normal solids discharge on one day, the treatment plant operations were
      otherwise stable during the year. As such, wastewater temperature appeared to be
      the dominant influence on the observed dynamics of the MFA community structure.
      MFA monitoring and analysis was demonstrated as a practical diagnostic tool in
      community structure trend monitoring. While the findings did suggest potential
      for full-scale treatment process monitoring, further development is required.
      Advancement in technique and greater insight for the data interpretation will be
      made with historical data from continued case studies. In future studies,
      selective sub-sampling of biomass fractions (settling and dispersed fauna),
      evolution in the compositional analysis methods, and, ideally, complementary
      genotypic and classical microscopic analyses on select samples are recommended.

PMID- 16898133
TI  - Ecophysiology and niche differentiation of Nitrospira-like bacteria, the key
      nitrite oxidizers in wastewater treatment plants.
AB  - Nitrite-oxidizing bacteria of the genus Nitrospira are key nitrifiers in
      wastewater treatment plants. Pure cultures of these organisms are unavailable,
      but cultivation-independent molecular methods make it possible to detect
      Nitrospira-like bacteria in environmental samples and to investigate their
      ecophysiology. Comprehensive screening of natural and engineered habitats and of
      public databases for 16S rRNA sequences of Nitrospira-like bacteria revealed a
      surprisingly high biodiversity in the genus Nitrospira, which comprises at least
      four phylogenetic sublineages. All Nitrospira-like bacteria detected in
      wastewater treatment plants belonged to the sublineages I and II. Subsequently,
      the population dynamics of different Nitrospira-like bacteria were monitored, by
      quantitative fluorescence in situ hybridization with rRNA-targeted probes,
      confocal laser scanning microscopy and digital image analysis, during incubation
      of nitrifying activated sludge in media containing different nitrite
      concentrations. These experiments showed that Nitrospira-like bacteria, which
      were affiliated with the phylogenetic sublineages I or II of the genus
      Nitrospira, responded differently to nitrite concentration shifts. Previously
      unknown properties of Nitrospira-like bacteria were discovered in the course of
      an environmental genomics project. Implications of the obtained results for
      fundamental understanding of the microbial ecology of nitrite oxidizers as well
      as for future improvement of nutrient removal in wastewater treatment plants are
      discussed.

PMID- 16898134
TI  - Microbial succession of glycogen accumulating organisms in an anaerobic-aerobic
      membrane bioreactor with no phosphorus removal.
AB  - The succession of glycogen accumulating organisms (GAOs) has been observed in an
      acetate-fed, anaerobic-aerobic sequencing membrane bioreactor (MBR) operated for
      260 days without enhanced biological phosphorus removal (EBPR) activity. Semi
      quantitative fluorescence in situ hybridization results showed that a
      gammaproteobacterial lineage GB frequently observed in EBPR processes was
      initially the numerically dominant species (50-66% of total cells) of the GAO in
      the MBR from day 1 to day 38. During this period, succession of two different
      subgroups of group GB was also observed. On day 85 onward, a population shift
      from GB group to 'Defluvicoccus'-related tetrad-forming organisms (TFO) occurred.
      This microbial succession was suspected to be related to the applied operating
      conditions (long hydraulic retention time and long solid residence time) which
      favored the proliferation of 'Defluvicoccus'-related TFO rather than the GB
      group. Application of terminal restriction fragment length polymorphism on
      selected samples further revealed that the microbial diversity of the seeding
      sludge as determined by the number of terminal restriction fragments was higher
      than that of sludge samples taken after day 85.

PMID- 16898135
TI  - Substrate uptake by Gordonia amarae in activated sludge foams by FISH-MAR.
AB  - Gordonia amarae is a right-angled branching filament belonging to the mycolic
      acid-containing Actinobacteria which is commonly found in many foaming activated
      sludge wastewater treatment plants. Although studies on different substrates as
      sole carbon sources by pure cultures of G. amarae have been carried out, none
      have examined substrate uptake by this organism in situ. Uptake of several
      hydrophilic and hydrophobic substrates by G. amarae was evaluated in situ using a
      combination of fluorescence in situ hybridization and microautoradiography. G.
      amarae could assimilate a range of both hydrophilic and hydrophobic substrates.
      From the data, G. amarae appears to be physiologically active under aerobic,
      anaerobic and anoxic condition (NO2 and NO3) for some substrates. This might
      explain why attempts to control foaming caused by G. amarae using anoxic and
      anaerobic selectors have been unsuccessful. This study emphasizes that bacteria
      can behave differently in situ to pure cultures and that it is important to
      evaluate the in situ physiology of these bacteria if we are to better understand
      their role in the wastewater treatment process.

PMID- 16898136
TI  - The in situ physiology of "Nostocoida limicola" II, a filamentous bacterial
      morphotype in bulking activated sludge, using fluorescence in situ hybridization
      and microautoradiography.
AB  - The in situ physiology of the actinobacterial bulking and foaming filamentous
      bacterium "Nostocoida limicola" II was studied by fluorescence in situ
      hybridization/microautoradiography. Substrate assimilation patterns of pure
      cultures of this bacterium were different to those seen in activated sludge
      biomass samples. There was no evidence to suggest that "N. limicola" II preferred
      hydrophobic substrates, but evidence was produced to support the view that it is
      metabolically active under anaerobic conditions in activated sludge.

PMID- 16898137
TI  - Gene cassette-associated sequences from phosphorus and non-phosphorus removing
      microbial communities in aerobic:anaerobic sequencing batch reactors.
AB  - Mobile gene elements associated with integrons, including as gene cassettes, have
      been proposed to play an important role in bacterial evolution by providing an
      extensive genetic resource. This study hypothesized that critical genes for
      enzymes involved in EBPR systems, including those involved in polyphosphate, PHA
      and glycogen synthesis, may be present in mobile gene cassettes. Although no such
      genes were identified in any of the functional and deteriorated enhanced
      biological phosphorus removal (EBPR) laboratory-scale SBR systems examined here,
      many of the open reading frames (ORFs) remained unidentified because of the
      incompleteness of publicly available databases. An ORF of unknown function (SBR6
      2) was encountered in deteriorated EBPR system with an unexpectedly high
      frequency, comprising 35% of the gene cassette-associated sequences for that
      system.

PMID- 16898138
TI  - Examining substrate uptake patterns of Rhodocyclus-related PAO in full-scale EBPR
      plants by using the MAR-FISH technique.
AB  - While recognised as the important population responsible for enhanced biological
      phosphorus removal (EBPR), detailed knowledge on the physiology of Rhodocyclus
      related polyphosphate accumulating organisms (PAO) has yet to be grasped. The
      objective of this study was to examine the in situ substrate uptake patterns of
      Rhodocyclus-related PAO present in full-scale EBPR plants by the combined
      technique of microautoradiography-fluorescent in situ hybridization (MAR-FISH).
      The presence of these PAO in the four investigated plants was confirmed by FISH
      and they constituted 17%, 9%, 8%, and 7% of the sludge community. By using MAR
      FISH technique, Rhodocyclus-related PAO in all the plants demonstrated similar
      anaerobic substrate uptake patterns. They were capable of assimilating acetate,
      aspartate and glutamate under anaerobic condition but they showed negative uptake
      with palmitate. A significant fraction of the MAR-positive cells assimilated
      acetate, aspartate or glutamate was found to be Rhodocyclus-related PAO. Dual
      staining with DAPI and FISH showed that these PAO also accumulated polyphosphate
      aerobically with aspartate and glutamate as carbon source. The ability of
      assimilating amino acids besides acetate strongly indicates the versatile
      physiology of Rhodocyclus-related PAO, which could benefit them to achieve
      predominance in EBPR activated sludge.

PMID- 16898139
TI  - Specific SBR population behaviour as revealed by comparative dynamic simulation
      analysis of three full-scale municipal SBR wastewater treatment plants.
AB  - Three full-scale municipal sequential batch reactor (SBR) wastewater treatment
      plants (WWTPs) were investigated by dynamic simulation studies using ASM1. All
      three WWTPs showed similar kinetic and stoichiometric conditions in the SBR
      population behaviour after calibration of the models. The simulation results
      detected only a discrepancy to the ammonia online data during and shortly after
      shock loading under anoxic and anaerobic conditions that so far could not be
      adjusted by the ASM1 model. However, these differences did not severely affect
      the quality of the simulations nor the effluent flows. Additionally, in all cases
      a dynamic alpha factor curve occurred during the aeration phases that was
      verified by further oxygen transfer measurements. This might reveal new aspects
      for the process control, design and simulation of SBR WWTPs. A short lag phase
      was detected in many cases at the beginning of the first aeration phase.

PMID- 16898141
TI  - Quantification of ammonia-oxidizing bacteria populations in full-scale sewage
      activated sludge systems and assessment of system variables affecting their
      performance.
AB  - This study carried out quantification of ammonia-oxidizing bacteria (AOB)
      populations in 12 full-scale sewage activated sludge systems that were different
      in ammonia removals and treatment processes during three different seasons.
      Experiment was divided into 3 parts: 1) analysis of AOB communities by PCR-DGGE
      cloning-sequencing of 16S rRNA genes; 2) development of four real-time PCR primer
      sets for quantification of the particular AOB of interest; and 3) quantification
      of AOB populations by using the newly developed real-time PCR primer sets. The
      results suggested that all the primer sets gave good reproducibility and
      specificity for PCR amplification with the detection limits of 10(2) copies/PCR
      reaction. Although the 12 systems were different in several aspects, one of the
      identified sequence types of Nitrosomonas oligotropha cluster was the dominant
      AOB in every system and every season studied. However, the other sequence type of
      this cluster was not significantly involved in ammonia removals in the systems.
      The occurrence of N. communis cluster in the systems seemed to depend on the
      remaining oxygen concentrations in the sludge floc and thus the activity of
      aerobic heterotrophs in the aeration tanks. N. europaea-Nitrosococcus. mobilis
      solely existed in one A20 system of which the influent contained twice the
      chloride concentrations than those of other systems.

PMID- 16898140
TI  - Microbial community of biological phosphorus removal process fed with municipal
      wastewater under different electron acceptor conditions.
AB  - The microbial community in a biological phosphorus removal process under
      different electron acceptor conditions was estimated by polymerase chain reaction
      denaturing gradient gel electrophoresis (PCR-DGGE) assay and principal-component
      analysis (PCA). For this purpose, a lab-scale sequencing batch reactor (SBR) fed
      with municipal wastewater was operated under anaerobic-aerobic, anaerobic-anoxic
      aerobic and anaerobic-anoxic conditions. The results of PCR-DGGE targeting the
      16S rRNA gene indicated a significant shift in the microbial community with
      electron acceptor conditions. From the 16S rRNA-based PCA, the microbial shift
      implies that little oxygen supply caused the deterioration of aerobic bacteria,
      including aerobic polyphosphate-accumulating organisms (PAOs). Moreover, it also
      reflects the existence of nitrate-utilizing denitrifiers. On the other hand,
      although the band patterns of DGGE targeting a functional gene of denitrification
      (nirS) also showed the microbial shift, the result of PCA differed from that of
      16S rRNA-based analysis. There is no conclusive proof that the bacteria
      represented as the dominant bands detected in the present study are denitrifying
      PAOs so far, it should be worthwhile to identify the detected bacteria and to
      examine their traits as new denitrifying-PAO candidates.

PMID- 16898142
TI  - Proliferation of glycogen accumulating organisms induced by Fe(III) dosing in a
      domestic wastewater treatment plant.
AB  - To meet the effluent requirements given for the sensitive receiving body, the
      Southpest Wastewater Treatment Plant of Budapest, Hungary uses a combined
      activated sludge-biofilter system with chemical precipitation for P removal.
      Causes of the proliferation of glycogen accumulating organisms (GAOs) observed in
      the unaerated/oxic activated sludge unit of this system were investigated both in
      full-scale and in lab-scale experiments combined with a detailed analysis of the
      microbial communities. Concentration profile measurements throughout the 8-stage
      activated sludge unit indicated anaerobic conditions in the first two unaerated
      reactors and low orthophosphate level (< 1 mg l(-1)) in all of the stages that
      could not be attributed to the influent quality, but to Fe (III)-dosing to the
      returned activated sludge. Microbiological analysis revealed the presence of GAOs
      from the GB group in the Gammaproteobacteria and occasionally tetrad-forming
      organisms from Actinobacteria, and the absence of Rhodocyclus-related
      polyphosphate accumulating organisms (PAOs) in the activated sludge samples.
      Comparative lab-scale studies carried out in two identically arranged UCT-systems
      with staged anoxic reactors also confirmed that Fe (III)-dosing may result in
      phosphorus deficiency of the microbial niche, leading to the suppression of
      growth and EBPR activity of PAOs and to the proliferation of GAOs.

PMID- 16898143
TI  - Fine-scale differences between Accumulibacter-like bacteria in enhanced
      biological phosphorus removal activated sludge.
AB  - A lab-scale sequencing batch reactor (SBR) and six full-scale wastewater
      treatment plants (WWTPs) performing enhanced biological phosphorus removal (EBPR)
      were surveyed. The abundance of Accumulibacter-related organisms in the full
      scale plants was investigated using fluorescent in situ hybridization.
      Accumulibacter-related organisms were present in all of the full-scale EBPR
      plants, at levels ranging from 9% to 24% of total cells. The high percentage of
      Accumulibacter-related organisms seemed to be associated with configurations
      which minimize the nitrate recycling to the anaerobic zone and low influent
      BOD:TP ratios. PCR-based clone libraries were constructed from the community 16S
      rRNA gene plus the internally transcribed spacer region amplified from the SBR
      and five of the full-scale WWTPs. Comparative sequence analysis was carried out
      using Accumulibacter-related clones, providing higher phylogenetic resolution and
      revealing finer-scale clustering of the sequences retrieved from the SBR and full
      scale EBPR

PMID- 16898144
TI  - Enrichment of activated sludge in a sequencing batch reactor for
      polyhydroxyalkanoate production.
AB  - The paper describes the start up of a process for the production of
      polyhydroxyalkanoates (PHAs) from activated sludge. The excess sludge from a
      wastewater treatment plant was inoculated in a lab-scale sequencing batch reactor
      (SBR) to be enriched under aerobic conditions through intermittent feeding with a
      mixture of organic acids. Enriching of activated sludge was monitored through the
      measurement of polymer concentrations either in the mixed liquor or in the
      microbial biomass. The bacterial population dynamics during the SBR start up was
      followed through denaturing gradient gel electrophoresis and the main species
      present at the steady state were identified. All the measured parameters
      significantly changed in the SBR during first two weeks after the inoculum was
      seeded into the reactor, they then stabilized. At the steady state, the SBR
      produced 2.6 gVSSl(-1) d(-1), with a PHA content of 11% (on a COD basis). The
      enriched microbial biomass was then transferred into a batch reactor where the
      bacterial polymer content was increased through a new feeding. In the final batch
      stage, maximum storage rate and maximum polymer content in the biomass were 405
      mgCOD gCOD(-1) h(-1) and 44% (on a COD basis), respectively. The PHA storage from
      the enriched microbial biomass was about 20 times faster and the PHA content was
      about 4 times higher than that of the inoculated activated sludge. Observations
      by fluorescence microscopy showed that the majority of microorganisms in the
      enriched biomass could be stored. Among the numerically most representative
      genera in the enriched biomass, Thauera, Candidatus Meganema perideroedes, and
      Flavobacterium were identified.

PMID- 16898145
TI  - Description of filamentous bacteria present in industrial activated sludge WWTPs
      by conventional and molecular methods.
AB  - Conventional cultivation methods and molecular approaches were utilised to
      describe the filamentous bacterial population of industrial activated sludge
      WWTPs. In total 43 strains were isolated by micromanipulation and were affiliated
      with 12 different species, comprising two new species and a new genus. In
      particular, a new species of Microthrix, a new genus of a filamentous
      Alphaproteobacteria morphologically similar to Nostocoida limicola, and a new
      filamentous species closely related to the opportunistic pathogen
      Propionibacterium propionicum were obtained. Despite the high number of isolates,
      the cultivation approach was unable to describe the filamentous bacteria most
      common in industrial WWTP. A culture-independent approach, termed the cell
      sorting/RT-PCR method, was therefore applied to identify fastidious or non
      culturable filamentous microrganisms from different industrial plants. By this
      method the relevant filaments were micromanipulated and their 16S rDNA genes were
      amplified by RT-PCR. This approach was highly efficient. In total 31 16S rRNA
      sequences were obtained and 16 of them were used for the design of new specific
      oligonucleotide probes that highlighted dominant filaments in industrial
      activated sludge plants.

PMID- 16898146
TI  - Microbial community structure of activated sludge during aerobic granulation in
      an annular gap bioreactor.
AB  - A novel annular gap reactor was designed to create a controlled shear environment
      in which aerobic granular sludge could be developed. The bacterial and eukaryal
      community structures during two aerobic granular sludge experiments were tracked
      using denaturing gradient gel electrophoresis (DGGE). The first granule
      cultivation experiment, using an organic loading rate of 1.6 kg/m3d COD, resulted
      in biomass that was dominated by filamentous bacteria and Zoogloea ramigera
      colonies. A second experiment with a higher organic loading rate of 6 kg/m3d COD
      developed a granule-like morphology but was ultimately dominated by filamentous
      fungi. Species identification via DGGE band purification and DNA sequencing
      closely matched the observed sludge morphology and behavior.

PMID- 16898147
TI  - Influence of flocculation and settling properties of activated sludge in relation
      to secondary settler performance.
AB  - Floc characteristics were studied at a full scale activated sludge treatment
      plant with a unique process solution incorporating pre-denitrification with post
      nitrification in nitrifying trickling filters. Since greater nitrogen removal is
      achieved when more secondary settled wastewater is recirculated to the trickling
      filters, the secondary settlers are always operated close to their maximal
      capacity. The flocculation and settling properties are therefore crucial and have
      an effect on the overall plant performance. Since the plant is operated at a
      short sludge age, these properties change quickly, resulting in variable maximal
      secondary settler capacity. The dynamics in floc structure and microbial
      community composition were studied and correlated to the secondary settler
      performance. Fluorescence in situ hybridisation was used to investigate the
      microbial community structure and their spatial distribution. The floc structure
      could to some extent be related to the flocculation and settling properties of
      the sludge. Even small differences had an influence suggesting that colloidal
      properties also play a significant role in determining the floc properties. No
      correlation between microbial community composition and settling properties could
      be established with the group-specific probes investigated.

PMID- 16898149
TI  - Use of image analysis for sludge characterisation: studying the relation between
      floc shape and sludge settleability.
AB  - This paper starts by presenting a fully automatic image analysis procedure for
      characterisation of flocs and filaments in activated sludge images. Thereafter
      the attention is directed towards the results of four lab-scale experiments, in
      which image information is related to sludge settleability in terms of sludge
      volume index. This relation is statistically confirmed by applying a principal
      component analysis to the data. In addition, the redundancy in the data sets is
      studied with regard to floc shape descriptors and the monitoring potential of
      image analysis is demonstrated by means of a multiple linear regression exercise.

PMID- 16898148
TI  - Evaluation of the impacts of model-based operation of SBRs on activated sludge
      microbial community.
AB  - Impact of model-based operation of nutrient removing SBRs on the stability of
      activated sludge population was studied in this contribution. The optimal
      operation scenario found by the systematic model-based optimisation protocol of
      Sin et al. (Wat. Sci. Tech., 2004, 50(10), 97-105) was applied to a pilot-scale
      SBR and observed to considerably improve the nutrient removal efficiency in the
      system. Further, the process dynamics was observed to change under the optimal
      operation scenario, e.g. the nitrite route prevailed and also filamentous bulking
      was provoked in the SBR system. At the microbial community level as monitored by
      DGGE, a transient shift was observed to gradually take place parallel to the
      shift into the optimal operation scenario. This implies that the model-based
      optimisation of a nutrient removing SBR causes changes at the microbial community
      level. This opens future perspectives to incorporate the valuable information
      from the molecular monitoring of activated sludge into the model-based
      optimisation methodologies. In this way, it is expected that model-based
      optimisation approaches will better cover complex and dynamic aspects of
      activated sludge systems.

PMID- 16898150
TI  - Protein extraction from activated sludge.
AB  - Two methods for the separation of protein originating from activated sludge were
      compared. In one method, the total protein was isolated out of the activated
      sludge (crude extract). These samples included all dissolved proteins originating
      from the bacterial cells and biofilm made up of extracellular polymeric
      substances (EPS). Every time polyacrylamide gel electrophoresis (PAGE) was done,
      the protein bands from samples of crude extract were covered by polymeric
      substances including carbohydrates, uronic acids or humic compounds. Using the
      immunoblot technique it was possible to demonstrate the presence of the heat
      shock protein HSP70 in crude extracts of activated sludge. The comparison of
      protein fingerprints required that clear and distinct bands appear on the PAGE
      analysis. To this end, a procedure to separates bacterial cells from the EPS was
      developed. Bacterial cells were separated by incubation with EDTA and subsequent
      filtration. The isolated cells were directly incubated in a sample buffer.

PMID- 16898152
TI  - Modelling seasonal dynamics of "Microthrix parvicella".
AB  - The filamentous bacteria "Microthrix parvicella" can cause serious bulking and
      scumming in wastewater treatment plants (WWTPs) all over the world. Decades of
      research have identified Microthrix as a specialized lipid consumer but could not
      clarify the processes that allow this organism to successfully compete in
      activated sludge systems. In this study we developed a model, based on ASM3, that
      describes the pronounced seasonal variations of Microthrix abundance observed in
      a full-scale WWTP. We hypothesize that low temperatures reduce the solubility of
      lipids and inhibit their uptake by non-specialized bacteria. The presented model
      structure and parameters successfully fit the measured data; however they do not
      necessarily reflect the only and true selection mechanism for Microthrix. This
      model is not yet to be used for prediction; it is rather a valuable research tool
      to coordinate the discussion and plan future research activities in order to
      identify the relevant selection mechanisms favoring Microthrix in activated
      sludge systems.

PMID- 16898151
TI  - Microbial community analysis with a high PHA storage capacity.
AB  - Activated sludge was submitted to aerobic dynamic substrate feeding for the
      production of biodegradable plastics. Two sequencing batch reactors were operated
      with acetate or propionate as sole carbon substrates. With acetate a homopolymer
      of polyhydroxybutyrate (PHB) was obtained and with propionate a copolymer of
      hydroxybutyrate and hydroxyvalerate P(HB/HV) was produced. Three main morphotypes
      were identified in both sludges: two belong to the Alphaproteobacteria class and
      the third to the Betaproteobacteria class. Bacilli belonging to
      Betaproteobacteria were shown by FISH analysis, applied in combination with Nile
      Blue post-staining, to be the main responsible for PHAs storage. The latter were
      affiliated to Azoarcus genus within Betaproteobacteria.

PMID- 16898153
TI  - Distributed microbial state effects on competition in enhanced biological
      phosphorus removal systems.
AB  - Computer simulation of activated sludge population dynamics is a useful tool in
      process design, operation, and troubleshooting, but currently available programs
      rely on the assumption of "lumped," or average, system characteristics in each
      reactor, such as microbial storage product contents. In reality, the states of
      individual bacteria are likely to vary due to variable residence times in
      reactors with completely mixed hydraulics. Earlier work by the present author
      introduced the MATLAB-based distributed state simulation program, Dissimulator
      1.0, and demonstrated that distributed states may be particularly important in
      enhanced biological phosphorus removal (EBPR) systems, which rely on the cycling
      of bacteria through anaerobic and aerobic reactors to select for a population
      accumulating multiple microbial storage products. This paper explores the
      relationships between distributed state profiles, variable anaerobic and aerobic
      SRTs, and the process rates predicted by lumped and distributed approaches.
      Consistent with previous results, the lumped approach consistently predicted
      better EBPR performance than did the distributed approach. The primary reason for
      this was the presence of large fractions of polyphosphate accumulating organisms
      (PAOs) with depleted microbial storage product contents, which led to
      overestimation of process rates by the lumped approach. Distributed and lumped
      predictions were therefore most similar when microbial storage product depletion
      was minimal. The effects of variable anaerobic and aerobic SRTs on distributed
      profile characteristics and process rates are presented. This work demonstrated
      that lumped assumptions may overestimate EBPR performance, and the degree of this
      error is a function of the distributed state profile characteristics such as the
      degree to which fractions of the biomass contain depleted microbial storage
      product contents.

PMID- 16898154
TI  - Microbial community development in a laboratory-scale nitrifying activated sludge
      system with input from a side-stream bioreactor treating digester supernatant.
AB  - Three laboratory-scale activated sludge treatment trains were operated to
      investigate the effect on biodiversity in plug flow (PFR) main-stream sewage
      treatment from input of biomass from side-stream reactors treating anaerobic
      digester supernatant. One train had a completely mixed (CSTR) side-stream
      reactor, one a PFR side-stream reactor, and the third train was a control that
      did not receive input from a side-stream reactor. Restriction endonucleases were
      used to digest polymerase chain reaction-amplified ammonia monooxygenase subunit
      A (amoA) genes in monthly samples from each reactor. Restriction fragment banding
      patterns from polyacrylimide gel electrophoresis indicated that the structure of
      the ammonia oxidizing bacteria (AOB) populations in all five reactors stabilized
      by the fourth month of operation and then did not vary subsequently. Furthermore,
      a dendrogram generated using the Jaccard distance showed that the AOB in each
      side-stream reactor was most similar to the main-stream reactor in the same train
      indicating that the AOB population in the side-stream reactor exerts a strong
      influence on the population in the main-stream reactor. Sequencing results
      indicated that Nitrosomonas europea, an r-strategist, was the dominant AOB in the
      PFR side-stream reactor, while Nitrosomonas europea and Nitrosomonas marina, a
      marine bacterium, were strongly represented in the CSTR side-stream reactor.

PMID- 16898155
TI  - Towards exposure of elusive metabolic mixed-culture processes: the application of
      metaproteomic analyses to activated sludge.
AB  - Protein expression is a direct reflection of specific microbial activities in any
      ecosystem. In order to assess protein expression in mixed microbial communities,
      the feasibility of applying proteomic techniques to activated sludge samples has
      recently been demonstrated. We report the application of metaproteomics to two
      activated sludges from a laboratory-scale sequencing batch reactor with
      dissimilar phosphorus removal performances. Fluorescence in situ hybridization
      (FISH) revealed that the sludge with good enhanced biological phosphorus removal
      performance (EBPR) was dominated by Betaproteobacteria (65% of EUBMIX binding
      cells) and gave positive signals for the Rhodocyclus-type PAO specific probe
      (59%). The non-EBPR sludge was dominated by tetrad-forming Alphaproteobacteria
      (75%). With regard to the proteomic investigation, 630 individual protein spots
      were matched across the replicate groups of the anaerobic and aerobic phases of
      the EBPR sludge with 9.4% of all spots being statistically different between the
      two phases. The non-EBPR metaproteomic maps exhibited 590 matched spots with
      14.7% statistical differences between the two phases. Overall, the non-EBPR
      sludge expressed around 30% more significant differences than the EBPR sludge.
      The comparison of protein expression in the two sludges showed that their
      metaproteomes were substantially different and this was reflected in their
      microbial community structures and metabolic transformations.

PMID- 16898156
TI  - Towards the design of diversity: stochastic models for community assembly in
      wastewater treatment plants.
AB  - We believe that the engineering of wastewater treatment systems would be improved
      if we could predict and manipulate the composition, that is, the diversity of
      such systems. This ability would complement our established ability to predict
      the size of treatment communities. The theoretically based design of diversity in
      wastewater treatment systems is held by some to be unnecessary and by others to
      be impossible. In this paper we point to important phenomena in wastewater
      treatment, such as acclimation, adaptation and functional redundancy that would
      benefit from the ability to confidently design diversity. We set out a rationale
      and a mathematical framework for a stochastic approach to the design of diversity
      and show that, in principle, this approach works with two important functional
      groups in wastewater treatment. The implications for design and theory are
      briefly discussed.

PMID- 16898157
TI  - Identity, abundance and physiology of Aquaspirillum-related filamentous bacteria
      in activated sludge.
AB  - Microcolony-forming bacteria closely related to the genus Aquaspirillum in the
      Betaproteobacteria were recently observed to be abundant in many nutrient removal
      wastewater treatment plants. The developed oligonucleotide probe, Aqs997,
      however, occasionally also targeted some filamentous bacteria in activated sludge
      samples when fluorescence in situ hybridization was performed. In this study, the
      identity, abundance, and ecophysiology of these Aqs997-positive filamentous
      bacteria were studied in detail. Most of the Aqs997-positive filamentous bacteria
      could morphologically be identified as either Eikelboom Type 1701, Type 0041/0675
      or possibly Type 1851, all characterized by epiphytic growth. They were found in
      almost all 21 wastewater treatment plants investigated. Two morphotypes were
      found. Type A filaments, which seemed to be the same genotype as the microcolony
      forming bacteria targeted by probe Aqs997.Type B filaments also hybridized with
      probe GNS941, specific for the Chloroflexi phylum, so the true identity remains
      unclear. Aqs997-positive filaments usually stained Gram-negative, but Gram
      positive filaments were also found, stressing the difficulties in identifying
      bacteria from morphology and simple staining results. Studies on the
      ecophysiology by microautoradiography showed that Aqs997-positive filamentous
      bacteria did not consume acetate and glucose, while some took up butyrate,
      mannose, and certain amino acids. Most likely, some Aqs997-positive filamentous
      bacteria were able to perform full denitrification such as the Aqs997-positive
      microcolony-forming bacteria, and some were able to store polyhydroxyalkanoates
      under anaerobic conditions, potentially being glycogen accumulating organisms.

PMID- 16898158
TI  - Effect of phosphorus limitation on microbial floc structure and gene expression
      in activated sludge.
AB  - The effect of limiting phosphorus (P) in activated sludge was investigated in
      laboratory-scale sequencing batch reactors (SBRs). Correlative microscopy
      revealed that P-limitation (COD:N:P = 100:5:0.05) leads to morphological changes
      in floc structure and the composition of extracellular polymeric substances
      (EPS). This was found to be accompanied by expression of quorum-sensing in an
      acyl homoserine lactone bioassay. Differential gene expression in relation to P
      limitation was examined in a global profile using the Affymetrix Escherichia coli
      antisense genomic microarray. Three separate experiments were conducted where the
      impact of P-limitation was examined under batch conditions and in SBRs at stable
      operating conditions and within 3-7 days following a down-shift in P. Significant
      changes in open reading frames (ORF) and intergenic regions based on the E. coli
      microarray were observed. Several genes associated with cell structure, including
      slt, wbbH, fimH, amB, rfaJ and slp were found to be expressed. Quorum regulated
      genes were also found to be expressed including psiF which is known to be induced
      by P-starvation (92% confidence level; 1.45 log ratio).

PMID- 16898159
TI  - Floc-forming properties of polyphosphate accumulating organisms in activated
      sludge.
AB  - The physico-chemical characteristics of polyphosphate-accumulating organisms
      (PAO) involved in enhanced biological phosphorus removal (EBPR) was investigated
      in order to find a novel method for phosphorus recovery. If the physico-chemical
      characteristics of PAO are different from those of other main floc components, it
      may be possible to enrich PAO in bulk water or in the floc material for improved
      recovery of phosphorus. A combination of shear tests, chemical manipulation, and
      quantification of PAO by fluorescence in situ hybridization was applied. The
      microcolony strength of both Rhodocyclus-related PAO and Actinobacteria-related
      PAO was generally high as no treatment could break up more than 20% of all PAO in
      microcolonies. In contrast, it was possible to remove 20-40% of the organic
      matter and other bacterial cells by applying a high pH value or adding EDTA. With
      that a selective enrichment of PAO in the remaining floc material was possible.
      The feasibility of applying this selective PAO enrichment in flocs remains to be
      evaluated in full-scale plants for P-recovery.

PMID- 16898160
TI  - Applicability of experience from laboratory reactors with biological phosphorus
      removal in full-scale plants.
AB  - Enhanced biological phosphorus removal (EBPR) has been used at many wastewater
      treatment plants all over the world for many years. In this study a full-scale
      sludge with good EBPR was tested with P-release batch tests and combined FISH/MAR
      (fluorescence in situ hybridisation and microautoradiography). Proposed models of
      PAOs and GAOs (polyphosphate- and glycogen-accumulating organisms) and microbial
      methods suggested from studies of laboratory reactors were found to be applicable
      also on sludge from full-scale plants. Dependency of pH and the uptake of both
      acetate and propionate were studied and used for calculations for verifying the
      models and results from microbial methods. All rates found from the batch tests
      with acetate were higher than in the batch tests with propionate, which was
      explained by the finding that only those parts of the bacterial community that
      were able to take up acetate anaerobically were able to take up propionate
      anaerobically.

PMID- 16898161
TI  - Construction and analysis of a metagenomic library from an enhanced biological
      phosphorus removal biomass.
AB  - The enhanced biological phosphorus removal (EBPR) process is regularly used for
      the treatment of wastewater, but suffers from erratic performance. Successful
      EBPR relies on the growth of bacteria called polyphosphate-accumulating organisms
      (PAOs), which store phosphorus intracellularly as polyphosphate, thus removing it
      from wastewater. Metabolic models have been proposed which describe the measured
      chemical transformations, however genetic evidence is lacking to confirm these
      hypotheses. The aim of this research was to generate a metagenomic library from
      biomass enriched in PAOs as determined by phenotypic data and fluorescence in
      situ hybridisation (FISH) using probes specific for the only described PAO to
      date, "Candidatus Accumulibacter phosphatis". DNA extraction methods were
      optimised and two fosmid libraries were constructed which contained 93 million
      base pairs of metagenomic data. Initial screening of the library for 16S rRNA
      genes revealed fosmids originating from a range of nonpure-cultured wastewater
      bacteria. The metagenomic libraries constructed will provide the ability to link
      phylogenetic and metabolic data for bacteria involved in nutrient removal from
      wastewater.

PMID- 16898162
TI  - The origin of hormesis: historical background and driving forces.
AB  - Copious historical reviews of Calabrese and Baldwin (Hum Exp Toxicol 2000; 19: 2
      31; 32-40) attribute the description of the reversal of cellular activities from
      stimulation at low doses to inhibition at high doses by Schulz (Pflug Arch 1988;
      42: 517-41) as the prioritizing contribution to the phenomenon which was later
      called hormesis. However, an extended search of the older literature uncovers
      Virchow (Virch Arch 1854; 6: 133-34) as the first descriptor, three and a half
      decades in advance of Schulz. Virchow observed an increase of the beating
      activity of the ciliae of tracheal epithelia of postmortem mucosa by sodium and
      potassium hydroxide at low concentrations, and a concentration-dependent decrease
      to arrest at higher concentrations. This observation constituted a cornerstone in
      Virchow's 'cellular pathology', which was based on the theory of cellular
      'irritation and irritability'. Schulz's experiment was essentially triggered by
      the psychiatrist Rudolf Arndt, an ardent protagonist of homeopathy. Schulz's pre
      occupation with homeopathic principles, which dominates his scientific oeuvre
      over his lifetime, may be seen as one of the reasons for the marginalization of
      hormesis.

PMID- 16898163
TI  - Evaluation of pteridine metabolism in battery workers chronically exposed to
      lead.
AB  - Occupationally-exposed lead affects the neuromuscular junction and might cause
      disturbances in the locomotor activity. This study was undertaken to evaluate
      pteridine metabolism, in which neurotransmitters are synthesized in battery
      workers. Urinary neopterin, biopterin and creatinine were measured using high
      performance liquid chromatography. Serum neopterin concentrations were detected
      by enzyme-linked immunoassay. Blood dihydropteridine reductase (DHPR) activities
      and deltaaminolevulinic acid (delta-ALA) were measured spectrophotometrically.
      Blood and urinary lead were detected by atomic absorption spectroscopy.
      Significantly increased blood and urinary lead levels, urinary neopterin,
      biopterin and delta-ALA were found in workers, while DHPR activities were
      indifferent compared to control group. Urinary creatinine decreased. This is the
      first study to demonstrate that increased activity of the pteridine pathway
      results in the accumulation of the neurotransmitters that may be responsible for
      the neurological disorders.

PMID- 16898165
TI  - Effect of prenatal exposure to bisphenol A on the serum testosterone
      concentration of rats at birth.
AB  - In the rat, testosterone (T) in the neonatal period plays an important role in
      sexual differentiation and there is a serum T surge in male rats 2 hours after
      birth. Pregnant female rats were exposed to various doses of bisphenol A (BPA)
      from gestational day 1 (GD1) through 2 hours after parturition. About half of the
      BPA-exposed and control dams were subjected to cesarean section on GD22. The male
      fetuses on GD22 were immediately sacrificed and blood was collected. The other
      half of the BPA-treated and control dams delivered at GD23 (parturition day). The
      male pups were sacrificed 2 hours after birth. Serum T concentration was
      determined by radioimmunoassay (RIA). The BPA concentration in the fetal serum on
      GD22 increased inversely to the T levels in the serum. The T concentration in the
      pups' serum 2 hours after birth decreased inversely to the BPA concentration in
      the serum. However, there were no differences in the serum T concentration among
      the various doses of BPA. These results suggest that exposure to BPA in utero
      inhibits the T surge in the neonatal period and we speculate that exposure to BPA
      in utero disrupts the endocrine environment in the neonatal male.

PMID- 16898164
TI  - Protective effects of ethanolic extract of Delphinium denudatum in a rat model of
      Parkinson's disease.
AB  - Parkinson's disease (PD) is one of the major neurodegenerative disorders, and
      oxidative stress has been implicated in playing an important role in the
      pathogenesis of the disease. In the present study, we investigated if Delphinium
      denudatum extract can slow down the neuronal injury in 6-hydroxydopamine (6-OHDA)
      rat model of Parkinsonism. Rats were treated with 200, 400 and 600 mg/kg body
      weight (b.w.) of D. denudatum extract for 3 weeks. On day 22, 2 microL of 6-OHDA
      (10 microg in 0.1% ascorbic acid-saline) or vehicle was infused into the right
      striatum of the animals. Three weeks after the 6-OHDA injections, the rats were
      killed for estimation of lipid peroxidation (LPO), reduced glutathione (GSH)
      content, superoxide dismutase (SOD) and catalase (CAT) activities,
      catecholamines, dopaminergic D2 receptor binding and tyrosine hydroxylase (TH)
      expression. Increased LPO and significant depletion of reduced GSH content in the
      substantia nigra resulting from the lesion were appreciably prevented with
      Delphinium treatment. Delphinium extract also dose-dependently attenuated the
      activities of SOD and CAT in striatum, which had been reduced significantly by
      lesioning. A significant decrease in the level of dopamine (DA) and its
      metabolites and an increase in the number of dopaminergic D2 receptors in
      striatum were observed after 6-OHDA injection, both parameters were significantly
      recovered with treatment of the extract. Finally, all these results were
      confirmed by an increase in expression of TH in the ipsilateral striatum of the
      lesioned groups following treatment with Delphinium extract. Thus, the study
      indicates that D. denudatum extract may be helpful in checking neuronal injury in
      Parkinsonism.

PMID- 16898166
TI  - Comparative study of the protective effect between deferoxamine and deferiprone
      on chronic iron overload induced cardiotoxicity in rats.
AB  - Patients with iron overload frequently suffer from hemochromatosis of major
      organs, such as the heart and liver. Heart affection is the most common cause of
      death in patients with iron overload. Although the beneficial effects of
      deferoxamine (DFO) on iron-associated mortality are well documented, the role of
      deferiprone in the management of transfusional iron overload is controversial.
      The aim of this study was to compare the protective effect of iron chelators (DFO
      and deferiprone) individually and in combination with the anti-oxidant (vitamin
      C) in the prevention of myocardial damage. Sixty albino rats were divided into
      six groups: two control groups (noniron-loaded and iron-loaded) and four iron
      loaded groups classified as follows: DFO group, DFO combined with vitamin C
      group, deferiprone group and deferiprone combined with vitamin C group. Heart
      tissue and blood samples were taken for histopathological examination of the
      heart, determination of total iron-binding capacity, 8-OH-deoxyguanosine (8-OH
      dG), myocardial lipid peroxidation and glutathione (GSH) content. Less
      histopathological cardiac changes and a significant decrease in all biochemical
      parameters, except myocardial GSH, were observed in the deferiprone group. The
      addition of vitamin C improves the biochemical and histopathological changes in
      comparison to those rats administered DFO or deferiprone individually.

PMID- 16898167
TI  - The local lymph node assay in practice: a current regulatory perspective.
AB  - Following the formal acceptance of the local lymph node assay (LLNA) as an
      Organization for Economic Cooperation and Development (OECD) guideline in April
      2002, the UK Health and Safety Executive (HSE) informed notifiers that this was
      now the method of choice for the assessment of skin sensitization potential under
      the EU notification scheme for new industrial chemicals (NONS). This paper
      summarizes the experience of the HSE for the 2-year period immediately following
      the issuing of this statement, during which 48 LLNA study reports were assessed
      for notification purposes. The issues discussed here include adherence to the
      OECD guideline, interpretation of results, and classification outcomes.
      Generally, notifying laboratories followed the OECD guideline successfully, with
      regard to the sex/ strain/numbers of mice used, the precise process used for
      measurement of cell proliferation, and the use of recommended vehicles and
      positive controls. Initially, use of the individual animal approach (measuring
      the cell proliferation in each animal rather than for a pooled dose group)
      highlighted problems caused by technical inexperience, but these were overcome by
      practice. Toxicity or irritation were found to be minor factors in dose
      selection; more important was the choice of vehicle to correctly maximize the
      test substance concentration, while maintaining appropriate application
      properties. Contrary to concerns that the LLNA would prove to be less sensitive
      or more sensitive than the traditionally used Guinea Pig Maximization Test
      (GPMT), the proportion of new substances classified as skin sensitizers was
      within the range observed in previous years. Although the sample size is
      relatively small, the experience of the HSE indicates that the LLNA is
      satisfactory for routine regulatory use.

PMID- 16898168
TI  - Hyperprolactinaemia as an adverse effect in regulatory and clinical toxicology:
      role in breast and prostate cancer.
AB  - Historically, hyperprolactinaemia has been considered of low toxicological
      relevance when detected in toxicity studies, and even mammary carcinogenesis
      induced in the rat by prolactin excess has been considered of no relevance to
      humans. However, recent findings from human epidemiology and molecular biology
      suggests that prolactin is a risk factor for human breast cancer, and probably
      prostate cancer. Therefore, this new evidence should be considered in the various
      decisions to develop and license a new drug or chemical if the compound causes
      hyperprolactinaemia. This emerging evidence suggests that prolactin can also be
      produced locally from human breast cancer cells, and that, regardless of source
      (ie, pituitary or autocrine/paracrine production from cancer cells), prolactin is
      mitogenic, stimulates proliferation and suppresses apoptosis in breast and
      prostate cancer cells. This review outlines the evidence that hyperprolactinaemia
      should be considered a toxicological adverse effect and concludes that prolactin
      induced rodent mammary carcinogenesis is relevant to humans and is not species
      specific. The effects of prolactin on the prostate gland are also discussed;
      hyperprolactinaemia may be an additional risk factor for prostate cancer and this
      also requires consideration in toxicological risk assessments. The implications
      of increased prolactin secretion as an adverse effect for regulatory toxicology
      of drugs and chemicals, and in high risk patients receiving therapeutic drugs
      with hyperprolactinaemic side effects, is discussed. Alteration of prolactin
      level is also a novel mechanism that requires consideration in endocrine
      disruption research, since both endogenous oestrogens and also xenoestrogens
      stimulate prolactin secretion or affect prolactin receptors.

PMID- 16898169
TI  - Mercury in traditional Tibetan medicine - panacea or problem?
AB  - Symptoms of mercury toxicity, biochemical changes, and blood/urine mercury levels
      were evaluated in a small group of patients. Six patients attending Delek
      Hospital, Dharamsala, India, taking mercury-containing traditional Tibetan
      medicine (TTM) (Group I), were compared with three patients taking non-mercury
      containing TTM (Group II) and healthy volunteers(Group II). Quantitative
      estimation of mercury ingestion based on chemical analysis was compared with US
      regulatory standards. RESULTS: Group I were significantly older (mean 55 years+/
      SE 6.4) range 26-69 years, than Group II (26.7 years+/-SE 5) range 17-34 years
      and Group III (32.5 years +/-SE 0.5) range 33-34 years (P =0.05). Group I took
      TTM on average for 51 months and had a mean of 2.5 non-specific, mercury-related
      symptoms. Group I had higher mean diastolic pressures (85 mmHg) than Group II (73
      mmHg) (P=0.06) and more loose teeth. Mean daily mercury intake for Group I was
      674 microg, estimated as 10 microg/kg per day. (Established reference dose for
      chronic oral exposure: 0.3 microg/kg per day.) Blood mercury levels were non
      detectable, but mean urinary mercury levels for Group I were 67 microg/L (EPA
      levels <20 microg/L). Renal and liver function tests were not significantly
      different between groups and within normal clinical range. CONCLUSIONS: Prolonged
      ingestion of mercury containing TTM is associated with absent blood levels, but
      relatively high urinary levels. Further studies are needed to evaluate toxicity
      and therapeutic potential.

PMID- 16898170
TI  - Critique of dose response in carcinogenesis.
AB  - A few landmarks in the development of dose response in toxicology are presented,
      with an explanation of why dose should only be considered on a logarithmic scale.
      Examples are shown, illustrating that the current practice of labeling dose
      response curves for carcinogenesis as supralinear, linear or sublinear, is
      meaningless unless the dose-response scales are defined. Since many reports
      labeling such curves as supralinear, linear, or sublinear are carried out with
      dose on a linear scale, the scientific significance of the shape of the curve is
      obscured. Examples of dose-response curves for carcinogenesis from 2
      acetylaminofluorene, N-nitrosodiethylamine, aflatoxins, and radium are shown. In
      addition, more than 500 National Toxicology Program Technical Reports (NTP-TR) on
      carcinogenicity were examined; from this database, three groups of studies were
      selected. The first group consisted of those studies in which the lowest dose
      produced no tumors and the study had a positive dose response. The second group
      consisted of those studies with three or more doses, with a positive dose
      response producing tumors, but in which there were no tumors in the control
      group. The third group of more than 50 studies was from NTP-TR-00 to NTP-TR-52
      that had only two data points with a positive dose response. These studies were
      all evaluated on the Rozman et al. scale, since it conforms to the laws of nature
      and allows evaluation of all doses. It was observed that virtually all of these
      NTP-TR carcinogenicity studies show a linear response when dose is on this
      logarithmic scale; a clear threshold for carcinogenicity is typical for nearly
      all of these chemicals. An exponential dose-response curve was a better fit for a
      few, but experimental error could account for this deviation from linearity. It
      is pointed out that there is strong experimental evidence that the mere presence
      of DNA adducts does not necessarily lead to tumor production. Hormesis probably
      applies to carcinogenesis and proof of this will require abandoning the no
      threshold concept. Experiments showing that cumulative dose is a better metric
      than daily dose may require reevaluating almost all carcinogenicity studies.

PMID- 16898171
TI  - European attempts to set guidelines for improving diagnostics of autoimmune
      rheumatic disorders.
AB  - The rational way to set a diagnosis and estimate a prognosis in rheumatology is
      to start by setting a tentative diagnosis and then follow a fixed scheme for
      laboratory testing, eg, by using an agreed algorithm. The use of order algorithms
      can be extended to post-test algorithms that will assist clinicians in
      approaching the right diagnosis and prognosis. New methods used in autoimmune
      serology do not deliver results that can be directly compared to those of older
      methods, and thus the new methods need to be thoroughly tested with sera from
      differential diagnostically relevant disease controls to set a clinically
      meaningful cut-off for positivity. Borderline positive results need to be treated
      with special care to avoid misuse. Early diagnosis is of great importance, and
      serological results can be very useful if used the right way. European efforts to
      secure rational diagnostic work-up in autoimmune rheumatic disease have led to a
      better dialogue between clinicians and laboratory scientists in several
      countries.

PMID- 16898172
TI  - Quantitation of autoantibodies in systemic autoimmune diseases: clinically
      useful?
AB  - Serial assessment of levels of autoantibodies has been proposed as being
      clinically useful in certain systemic autoimmune diseases. In particular,
      attention has been given to anti-dsDNA antibodies in systemic lupus erythematosus
      (SLE) and ANCA in the ANCA-associated vasculitides (AAV). Much controversy
      exists, however, concerning the value of serial testing in these diseases. We
      here review the various tests available for quantitation of anti-dsDNA and ANCA,
      and their capacity to detect changes in autoantibody levels that are associated
      with changes in clinical disease activity of the respective diseases. It is
      concluded that changes in anti-dsDNA as measured by the Farr assay and changes in
      ANCA as assessed by ELISA have predictive value for the occurrence of disease
      relapses, although this relationship is far from absolute. Consequently,
      treatment based on changes in levels of the respective autoantibodies only seems
      at present not justified, in view of the toxicity of currently available
      immunosuppressive regimens.

PMID- 16898173
TI  - Detection of antibodies to dsDNA: an overview of laboratory assays.
AB  - This brief review is focused on different methodologies available for detection
      of anti-dsDNA antibodies with respect to the best adequacy between biological
      results of laboratory and clinical significance. A large array of assays has been
      developed for the measurement of anti-dsDNA. New assays continually introduced
      have reflected not only technical innovations to avoid difficulties of some
      assays, but even more with hope to correlate better with systemic lupus
      erythematosus (SLE), particularly with its clinical course and exacerbations.
      Finally, with the development of micro arrays technology new insights into the
      pathophysiology of autoimmune disease processes should be revealed.

PMID- 16898174
TI  - Anti-chromatin (anti-nucleosome) antibodies.
AB  - Chromatin is the native complex of histones and DNA found in the cell nucleus of
      eukaryotes. The fundamental subunit of chromatin is the nucleosome, which is
      composed of a core particle in which 146 bp of helical DNA are wrapped around an
      octamer made up of two H2A-H2B dimers that surround an H3-H4 tetramer. The
      prevalence of anti-chromatin (nucleosome) antibodies in systemic lupus
      erythematosus (SLE) varies from 50% to 90%, being similar to that of the
      classical positive LE cell. The presence of these antibodies can be used, in
      conjunction with clinical findings and other laboratory tests, to help in the
      diagnosis of SLE and drug induced lupus. The presence of anti-chromatin
      antibodies has also been linked to glomerulonephritis in SLE patients.

PMID- 16898175
TI  - Autoantibody detection using multiplex technologies.
AB  - Measurement of multiple antibodies has been possible for years using labor
      intensive methods such as counterimmunoelectrophoresis and
      radioimmunoprecipitation. Recently, simpler methods that are more practical for
      routine analysis, often described as multiplex technologies, have been
      introduced. One common technique, the line assay, uses nitrocellulose strips that
      are precoated at different locations with more than a dozen recombinant proteins
      or peptides. Detection of results may be performed visually or with scanning
      instrumentation. A second technique uses families of polystyrene beads that are
      dyed to establish a unique identity; each bead type is then coated with a
      specific affinity-purified or recombinant protein. Detection is performed by flow
      cytometry. There have been multiple descriptions of the use of these techniques
      for measuring antibodies associated with the antinuclear antibody screen. More
      recent reports describe applications to antibodies associated with
      hypothyroidism, ANCA, anti-phospholipid syndrome, and celiac disease. This review
      summarizes the work that has been performed to date and examines the potential
      benefits of multiplexing to both the laboratory and the physician.

PMID- 16898176
TI  - Advances and applications of multiplexed diagnostic technologies in autoimmune
      diseases.
AB  - There is a rapid proliferation of new technologies to identify an ever increasing
      spectrum of autoantibodies in diverse medical conditions that range from organ
      specific autoimmune diseases to systemic rheumatic diseases. Although many
      laboratories have adopted diagnostic platforms, such as enzyme linked
      immunoassays (ELISAs), to improve turn around times and meet budget constraints,
      the prevailing evidence is that the rapid adoption of new technologies is not
      attended by an appropriate balance of assay sensitivity and specificity. Emerging
      diagnostic technologies include addressable laser bead immunoassays, microarrays
      in microfluidics platforms and nanobarcode particles. Although these technologies
      provide advantages of high-throughput, multiplexed autoantibody assays that can
      be coupled to other disease specific biomarkers (ie, cytokines, single nucleotide
      polymorphisms) there is a clear need for standardization and internal validation
      before they are adopted into the clinical diagnostic laboratory.

PMID- 16898177
TI  - Antigen-chip technology for accessing global information about the state of the
      body.
AB  - Traditionally, immunologic diagnosis has been based on an attempt to correlate
      each disease with a specific immune reactivity, such as an antibody or a T-cell
      response to a single antigen specific for the disease entity. The state of the
      body, however, appears to be encoded by the immune system in collectives of
      reactivities and not by single reactivities. Here we describe our use of
      microarray technology and informatics to develop an antigen chip capable of
      detecting global patterns of antibodies binding to hundreds of antigens
      simultaneously. The patterns fashion diagnostic signatures.

PMID- 16898178
TI  - Use of proteomics in analysis of autoimmune diseases.
AB  - Autoimmune diseases are common by diseases characterized by disorders of immune
      responses and autoimmune impairment involving multiple tissues, organs and
      systems. The autoantigens (Ags)/autoantibodies (Abs) are not only hallmarks but
      also involved in pathogenesis of autoimmune diseases. In recent years, proteomics
      technologies have been used and demonstrated effective in searching new Ags/Abs
      as well as disease biomarkers in autoimmune diseases.

PMID- 16898179
TI  - Application of a static fluorescence-based cytometer: the CellScan in clinical
      immunology.
AB  - The CellScan system is a laser scanning cytometer which enables repetitive
      fluorescence intensity (FI) and polarization (FP) measurements in living cells,
      as a means of monitoring lymphocyte activation. By monitoring FP changes in
      peripheral blood lymphocytes (PBL) following exposure to antigenic stimuli, the
      CellScan may have a role in the diagnosis of autoimmune diseases. Monitoring
      changes in FI and FP in PBLs from patients with atherosclerosis following
      exposure to various stimuli, has illustrated the role of the immune system in the
      atherosclerotic process. The CellScan has also been evaluated as a diagnostic
      tool for drug-induced allergy, based on FP reduction in PBLs following incubation
      with the suspected drugs. FI and FP changes in cancer cells have been found to
      correlate with the cytotoxic effect of different anti-neoplastic drugs,
      illustrating the potential role of the CellScan system in clinical oncology. In
      conclusion, the CellScan is a promising new tool with a variety of applications
      in cell biology, immunology, cancer research and clinical pharmacology.

PMID- 16898180
TI  - Anti-glycan antibodies as biomarkers for diagnosis and prognosis.
AB  - Glycans (sugars or carbohydrates) are predominant surface components of cells
      such as erythrocytes, immune cells and microorganisms. As such, they give rise to
      high levels of anti-glycan antibodies of all classes. Antibodies to certain
      defined mono, di and oligosaccharides that are common in bacterial, fungal and
      parasite cells exist in human sera and can be profiled using glycan arrays. The
      use of glycan arrays for systematic screening of blood samples from multiple
      sclerosis (MS) and Crohn's disease (CD) patients in versus to blood samples from
      control groups, have lead to the discovery of a few anti glycan antibodies
      biomarkers enabling diagnosis and prognosis in MS and CD patients. Anti
      Glc(alpha1,4)Glc(alpha) IgM antibodies were found to be specific for MS patients,
      enabling differentiation between MS patients and patients with other neurological
      diseases, with 54% sensitivity and 85% specificity. Anti-Glc(alpha1,4)Glc(alpha)
      IgM were found to be predictive for the conversion of patients in first acute
      neurological event to clinically defined MS. Anti-laminaribioside (ALCA), anti
      mannobioside (AMCA) and anti-chitobioside (ACCA) antibodies were found to be
      specific for CD. The combined use of these antibodies enables improved diagnosis
      of CD versus ulcerative colitis and other gastrointestinal diseases, as well as
      stratification of CD patients with a more complicated disease and high risk for
      surgery. Anti-glycan antibodies profiling (AGAP) is a new and promising approach
      for development of biomarkers for diagnosis and prognosis.

PMID- 16898181
TI  - Gene expression studies in systemic lupus erythematosus.
AB  - In a single assay, gene microarrays generate tens of thousands of measurements
      for the relative levels of messenger RNA expression, and thus hold promise to
      uncover the regulation of transcriptional responses behind clinical phenotypes of
      various diseases. Systemic lupus erythematosus (SLE) offers a unique opportunity
      to study gene expression both systemically and organ specific, as the tissues
      involved and specifically peripheral blood cells are readily accessible for
      molecular analysis. In the current review we highlight the current knowledge
      related to gene microarray in SLE. We approached the following questions: 1) Can
      gene microarray technology be used to translate molecular profiles into
      meaningful and applicable clinical information? 2) Does the assessment of
      differential gene expression provide specific signatures that may contribute to
      diagnostic and prognostic markers of SLE? 3) Can clinicians be helped in
      monitoring disease activity by identification of drug response gene profile? 4)
      Does evaluation of differential gene expression provide clues to detect
      previously unrecognized genes associated with the disease? It is evident that
      though not all questions can be currently answered appropriately, gene expression
      studies in SLE have important implications and will not only be beneficial for
      SLE patients, but will also lead to a better understanding of other autoimmune
      inflammatory diseases, thereby leading to novel diagnostic and therapeutic
      strategies in autoimmunity.

PMID- 16898182
TI  - Measurement of electrical skin impedance of dermal-visceral zones as a diagnostic
      tool for disorders of the immune system.
AB  - Among complementary medicine approaches, diagnostic screening tools based on
      neuroreflexology have been recently developed. Such techniques are based on the
      rationale that measurement of electrical impedance of specific dermal zones might
      reflect the occurrence of pathological states in the corresponding internal
      organs or systems. Our objective was to evaluate the reliability of a
      neuroreflexology-based diagnostic test in diagnosing immune-mediated diseases in
      a blinded single centre study. Seventy-eight patients with immune-mediated
      diseases (38 patients with autoimmune diseases (AD), and 40 allergic patients)
      were included in the study. Thirty age and sex matched healthy subjects were also
      evaluated as a control group. All the patients and subjects underwent
      conventional medical history and physical examination. We evaluated a device
      manufactured by Medex Screen Ltd (Arad, Israel). The Medex Test analysis was
      carried out by a second physician who was blinded to the previous diagnosis. A
      high correlation between the formal clinical diagnosis and the results of the
      measurement of electrical skin impedance was reported, with a specificity of
      93.3% and a sensitivity of 81.2%. Both sensitivity and specificity dropped when
      analysing the autoimmune and the allergic group separately, but remained
      significant for the autoimmune diseases. Degree of activity of the allergic
      disorders, or specific treatment, did not affect the diagnostic properties of the
      described device. The Medex Test neurophysiology based technique has the
      potential to serve as a diagnostic tool for immune based pathologies. Future
      studies will define this tool place in routine evaluation and potential screening
      ability.

PMID- 16898183
TI  - Insights in the laboratory diagnosis of celiac disease.
AB  - The present report focuses on the diagnosis of celiac disease and its
      pathogenesis, which depends on a genetic predisposition (HLA DQ2 or DQ8
      haplotypes), gluten ingestion and T cell activation, type II transglutaminase
      (TG2), the autoantigen recognized by the antiendomysial antibody playing a key
      role. IgA class antibody anti-environmental (gliadin) and endogenous (TG2)
      antigens are present in the sera of patients with celiac disease. The anti-TG2
      antibody has the best available diagnostic accuracy, especially when measured
      employing second generation ELISA tests, which use the human TG2 antigen, or
      immunochemiluminescent assay, which is highly sensitive. A diagnosis of celiac
      disease must always be confirmed by the histological evaluation of multiple
      duodenal mucosa specimens, and serology is recommended for follow-up controls.

PMID- 16898184
TI  - Stenosis in antiphospholipid syndrome: a new finding with clinical implications.
AB  - Antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized
      by a variety of clinical manifestations. Recent studies suggest arterial stenosis
      is involved in APS. Furthermore, arterial stenosis may be a relevant and
      treatable cause for hypertension, renal, CNS and gastrointestinal manifestations
      of APS. Our objective was to overview the published data regarding arterial
      stenosis in APS--the clinical presentation, diagnosis, suggested therapies and
      the possible mechanisms. We searched PUBMED (1951-2006) reference lists for the
      role of arterial stenosis in APS. APS patients might present with arterial
      stenosis. Its recognition has important diagnostic and therapeutic implications.
      Articles suggest that anticoagulation treatment with INR above three may reverse
      the artery stenosis and achieve subsequent clinical improvement. Currently, there
      are no specific guidelines for the management of APS patients with arterial
      stenosis. The exact mechanism of arterial stenosis in APS patients remains
      unclear.

PMID- 16898185
TI  - Autoimmune hemolytic anaemia in the antiphospholipid syndrome.
AB  - Antiphospholipid syndrome (APS) is a multisystem disease with recurrent
      thrombosis in the presence of antiphosphlipid antibodies, which may include
      cardiac, neurological, gastrointestinal, hematologic or cutaneous manifestations.
      The occurrence of autoimmune hemolytic anaemia (AIHA) in APS has not been well
      established. The purpose of this study was to review the occurrence of AIHA in
      patients with APS and its relation to other disease manifestations. Three-hundred
      and eight patients with APS from seven medical centers in Israel, Serbia and the
      Slovac Republic were included and evaluated for associations between AIHA and
      various manifestations of APS. AIHA was documented in 32 patients (10.4%). The
      odds ration for AIHA was increased in the presence of anticardiolipin antibodies
      and livedo reticularis (5.4 and 7.8, respectively). There was a highly
      significant association between AIHA and cardiac valvular vegetations and
      thickening (P < 0.0001), arterial thrombosis (P < 0.02), livedo reticularis (P <
      0.0001) and CNS signs of epilepsy or chorea (P < 0.02 and P < 0.03,
      respectively). Thus, APS patients with AIHA are at risk of developing these
      manifestations, and should therefore be investigated for them. In addition, the
      occurrence of AIHA may define a subgroup of patients with a significant risk for
      subsequent development of SLE.

PMID- 16898186
TI  - Atherogenic oxidized low-density lipoprotein/beta2-glycoprotein I
      (oxLDL/beta2GPI) complexes in patients with systemic lupus erythematosus and
      antiphospholipid syndrome.
AB  - Oxidized low-density lipoprotein (oxLDL) interacts in vitro with beta2
      glycoprotein I (beta2GPI) via LDL-derived specific ligands forming oxLDL/beta2GPI
      complexes. Circulating oxLDL/beta2GPI complexes have been demonstrated in
      patients with systemic lupus erythematosus (SLE) and antiphospholipid syndrome
      (APS). Autoimmune vascular inflammation and oxidative stress contribute to
      oxLDL/beta2GPI complex formation. Immunohistochemical staining of atherosclerotic
      lesions suggest that these complexes are formed in the arterial wall and released
      into circulation. The demonstration of antibodies to oxLDL/beta2GPI complexes
      indicates that these complexes are immunogenic, and the coexistence of complexes
      and antibodies suggest an active pro-thrombotic/pro-atherogenic role in the
      development of autoimmune vascular complications. Circulating oxLDL/beta2GPI
      complexes can be measured by ELISA using a monoclonal antibody specific to
      complexed human beta2GPI to capture beta2GPI bound to oxLDL. An enzyme-conjugated
      monoclonal antibody to human Apo B 100 allows the specific detection of
      oxLDL/beta2GPI complexes. OxLDL/beta2GPI complexes were common in SLE and APS
      patients suggesting an underlying process of inflammation and oxidation. Using
      oxLDL/beta2GPI complexes as capture antigen, antibodies to oxLDL/beta2GPI can be
      measured by ELISA. Serum levels of IgG anti-oxLDL/beta2GPI antibodies were
      significantly higher in SLE patients with APS compared to SLE controls without
      APS. Further, high titers of these IgG antibodies were observed in APS patients
      with a history of arterial thrombosis. The presence of circulating oxLDL/beta2GPI
      complexes and IgG antibodies to these complexes indicates significant vascular
      injury and oxidative stress as well as an active role in autoimmune-mediated
      atherothrombosis.

PMID- 16898188
TI  - How should the government check nurses are fit to practise?

PMID- 16898189
TI  - Taking the strain.

PMID- 16898190
TI  - Snap decisions.
AB  - Innovative ways of making children's voices heard to shape services are being
      supported by the Picker Institute charity as part of its Patients Accelerating
      Change scheme. These include photographic projects at two NHS trusts.

PMID- 16898191
TI  - A short step to health.
AB  - Led walks have become a popular activity around the country, improving physical
      and mental health and reducing social isolation. Now the Department of Health is
      introducing dedicated staff as health trainers.

PMID- 16898192
TI  - Home is where the hate is.
AB  - Domestic violence and abuse are areas where health professionals often fear to
      tread, feeling that they have insufficient information and expertise to be able
      to help. But a Department Health publication is there to provide guidance.

PMID- 16898193
TI  - Patients were reassured when I expressed my distress at death.

PMID- 16898194
TI  - Fear of reprisals keeps us quiet.

PMID- 16898195
TI  - Case against prosecution.

PMID- 16898196
TI  - A new way of caring for older people in the community.
AB  - The government's modernisation agenda is challenging traditional practice by
      introducing new roles and concepts to meet the increasing healthcare needs of the
      older population and those with long-term conditions. Over the past two years
      several national pilots have been trialled to examine different models of
      managing care for these groups. One is the Evercare model, a case management
      approach to the delivery of care in the community for older people. This article
      focuses on a cohort of 12 nurses from three local primary care trusts who
      participated in the national Evercare pilot project from July 2003-April 2005. It
      examines the context for change, explores and appraises the development of a new
      role, and evaluates the educational partnership developed with a local
      university.

PMID- 16898197
TI  - Ankylosing spondylitis.
AB  - This article provides an overview of ankylosing spondylitis, a chronic condition
      characterised by abnormal ossification and ankylosis affecting the spine and
      sacro-iliac joints. It explores the needs of patients with the condition and
      identifies pharmacological and non-pharmacological approaches to disease
      management.

PMID- 16898198
TI  - Managing pain in patients with dementia in hospital.
AB  - This is the fourth article in a series of five on dementia. Pain experienced by
      people with dementia is often poorly managed. Chronic pain can lead to further
      cognitive impairment, accidents and behavioural problems which can be minimised
      if the pain is properly assessed and managed. Patients with dementia receive
      fewer analgesics than any other patient group, but the likelihood of pain in this
      group is as high as in other older people. This article discusses the role of
      nurses in identifying and treating pain in patients with dementia. Approaches to
      assessment for improved detection and treatment of pain are outlined.

PMID- 16898201
TI  - Too posh to floss?

PMID- 16898199
TI  - Learning to nurse: reflections on bathing a patient.
AB  - The reflective process allows nurses to view their practice by bringing their
      theoretical knowledge and nursing practice closer together. In this article, a
      nursing student describes different methods of reflection and applies them to her
      experience of bathing a patient. Issues of bathing, preparation and the conflicts
      with time management are explored, demonstrating the benefits of reflection as a
      tool for learning.

PMID- 16898200
TI  - Diet for older people.

PMID- 16898202
TI  - Hang on in there.

PMID- 16898203
TI  - Confidence boost.

PMID- 16898204
TI  - Laws, causation, and explanation in the special sciences.
AB  - There is the general philosophical question concerning the relationship between
      physics, which is often taken to be our fundamental and all-encompassing science,
      on one hand and the special sciences, such as biology and psychology, each of
      which deals with phenomena in some specially restricted domain, on the other.
      This paper deals with a narrower question: Are there laws in the special
      sciences, laws like those we find, or expect to find, in basic physics? Three
      arguments that are intended to show that there are no such laws are presented and
      examined. The paper ends with brief remarks concerning the implications of these
      arguments for explanation and causation in the special sciences.

PMID- 16898205
TI  - Defending information-free genocentrism.
AB  - Genocentrism, the thesis that the genes play a special role in the causation of
      development is often rejected in favor of a 'causal democracy thesis' to the
      effect that all causally necessary conditions for development are equal.
      Genocentrists argue that genes play a distinct causal role owing to their
      informational content and that this content enables them to program the embryo. I
      show that the special causal role of the genome hinges not on its informational
      status--it has none, or at least no more than computer programs have independent
      of our interpretations of them--but on its power literally to program the embryo,
      a power nicely illustrated in the use of polynucleotide sequences to compute
      solutions to NP hard problems in mathematics.

PMID- 16898206
TI  - Epidemiological causality.
AB  - Epidemiological methods, which combine population thinking and group comparisons,
      can primarily identify causes of disease in populations. There is therefore a
      tension between our intuitive notion of a cause, which we want to be
      deterministic and invariant at the individual level, and the epidemiological
      notion of causes, which are invariant only at the population level.
      Epidemiologists have given heretofore a pragmatic solution to this tension.
      Causal inference in epidemiology consists in checking the logical coherence of a
      causality statement and determining whether what has been found grossly
      contradicts what we think we already know: how strong is the association? Is
      there a dose-response relationship? Does the cause precede the effect? Is the
      effect biologically plausible? Etc. This approach to causal inference can be
      traced back to the English philosophers David Hume and John Stuart Mill. On the
      other hand, the mode of establishing causality, devised by Jakob Henle and Robert
      Koch, which has been fruitful in bacteriology, requires that in every instance
      the effect invariably follows the cause (e.g., inoculation of Koch bacillus and
      tuberculosis). This is incompatible with epidemiological causality which has to
      deal with probabilistic effects (e.g., smoking and lung cancer), and is therefore
      invariant only for the population.

PMID- 16898207
TI  - Causality and methodology. Notes on thanatochronological estimations.
AB  - The authors propose some methodological considerations on thanatochronological
      estimations. They first consider the problem of the definition of death, and then
      they deal with the issue of the estimations of death time, that is, with the Post
      Mortem Interval (PMI). As regards the first question, they note that it does not
      concern only the definition of death, but also the choice of a particular kind of
      definition of 'definition'. With reference to the second question, the authors
      suggest a causal model showing that the presence of many causal chains must be
      taken into consideration. Finally they discuss what 'most convenient and reliable
      causal chain' means for a thanatochronologist.

PMID- 16898208
TI  - Chance, explanation, and causation in evolutionary theory.
AB  - Chance comes into plays at many levels of the explanation of the evolutionary
      process; but the unity of sense of this category is problematic. The purpose of
      this talk is to clarify the meaning of chance at various levels in evolutionary
      theory: mutations, genetic drift, genetic revolutions, ecosystems,
      macroevolution. Three main concepts of chance are found at these various levels:
      luck (popular concept), randomness (probabilistic concept), and contingency
      relative to a given theoretical system (epistemological concept). After
      identifying which concept(s) of chance fit(s) with these levels, the question is
      raised whether these concepts can be reduced to a smaller number, and whether
      chance in evolutionary theory has a subjective or an objective sense.

PMID- 16898210
TI  - The causal homogeneity of biological kinds.
AB  - The aim of this paper is to show that biological kinds can be causally
      homogeneous, although all biological causes are identical with configurations of
      physical causes. The paper considers two different strategies to establish that
      result: the first one relies on two different manners of classification
      (according to function and according to composition); the other one exploits the
      idea of biological classifications being rather coarse-grained, whereas physical
      classifications are fine-grained.

PMID- 16898209
TI  - Genes, causation and intentionality.
AB  - I want to exhibit the deeper metaphysical reasons why some common ways of
      describing the causal role of genes in development and evolution are problematic.
      Specifically, I show why using the concept of information in an intentional sense
      in genetics is inappropriate, even given a naturalistic account of
      intentionality. Furthermore, I argue that descriptions that use notions such as
      programming, directing or orchestrating are problematic not for empirical
      reasons, but because they are not strictly causal. They are intentional. By
      contrast, other notions that are part of the received view in genetics and
      evolutionary theory are defensible if understood correctly, in particular the
      idea that genes are the main replicators in evolution. The paper concludes that
      dropping all intentional or intentionally laden concepts does not force us to
      accept the so-called causal parity thesis, at least not in its stronger form.

PMID- 16898211
TI  - Reduction of biological properties by means of functional sub-types.
AB  - The general aim of this paper is to propose a reductionist strategy to higher
      level property types. Starting from a common ground in the philosophy of science,
      I shall elaborate on possible realizer differences of higher-level property
      types. Because of the realizer types' causal heterogeneity, an introduction of
      functional subtypes of higher-level properties will be suggested. Each higher
      level functional sub-type corresponds to one realizer type. This means that there
      is the theoretical possibility to reach some kind of type-identity and this opens
      up the way for theory reduction in a more complete manner. This kind of type
      identity will go beyond the common ground of the identity of tokens and their
      reductive explanation. In the second part of the paper, this reductionist
      strategy will be applied to a specific debate in the philosophy of biology--the
      reductionist approach to classical genetics from a molecular point of view.

PMID- 16898212
TI  - Diderot, Cabanis and Lamarck on psycho-physical causality.
AB  - Modern physics was born in the 17th century and modern biology one century later.
      Immediately, scientifics and philosophers ask themselves what is the relationship
      between those two sciences and between properties of non-living and living
      matter. Among those scientifics and philosophers, some think that mental
      phenomena are of biological nature--they are materialists--so they encounter a
      second problem: what is the relationship between properties of non-thinking and
      thinking living matter? This paper examines the doctrine of three French
      philosophers of the (post-) Enlightenment on those subjects: Diderot, Cabanis and
      Lamarck, and, as their answer is in terms of causality and supervenience, I
      compare succinctly their doctrine with those of Searle and Kim.

PMID- 16898213
TI  - Causation and space-time.
AB  - This paper considers the physical accounts of causation in terms of conserved
      quantities in the light of the theory of general relativity. As it is rather well
      known among physicists, there are several difficulties with the notions of
      conservation and localization of the (gravitational) energy-momentum within
      general relativity. We first begin to review the so-called conserved quantity
      theory of causation mainly due to Dowe and Salmon, then we discuss some
      consequences of these difficulties for this physical account of causation. We
      argue that these difficulties are due to the fundamental nature of the space-time
      structure as described by GR, which the conserved quantity theory of causation
      does not account for.

PMID- 16898214
TI  - Counterfactual overdetermination vs. the causal exclusion problem.
AB  - This paper aims to show that a counterfactual approach to causation is not
      sufficient to provide a solution to the causal exclusion problem in the form of
      systematic overdetermination. Taking into account the truthmakers of causal
      counterfactuals provides a strong argument in favour of the identity of causes in
      situations of translevel, causation.

PMID- 16898215
TI  - A realist approach to biological events.
AB  - In this paper, I aim to show that the multiple realisability and the causal
      efficacy of biological events can best be explained by construing biological
      events as determinables of more determinate physical events. The determination
      relation itself is spelled out in terms of inclusive essence. In order to secure
      actual causation for biological events (in contrast to causal influence), two
      conditions are introduced such that for some events, biological events qualify as
      their cause. Finally, certain consequences of the presented theory are discussed,
      such as the question of how the biological token event can retain its identity
      across modal modifications of its realiser, and such as how the presented
      solution bears on the classical problem of biological causation.

PMID- 16898216
TI  - Compliant layer acetabular cups: friction testing of a range of materials and
      designs for a new generation of prosthesis that mimics the natural joint.
AB  - Total joint replacements (TJRs) have a limited lifetime, but the introduction of
      components that exhibit good lubricating properties with low friction and low
      wear could extend the life of TJRs. A novel acetabular cup design using
      polyurethane (PU) as a compliant layer (to mimic the natural joint) has been
      developed. This study describes a series of friction tests that have been used to
      select the most appropriate material, optimize the design parameters, and fine
      tune the manufacturing processes of these joints. To determine accurately the
      mode of lubrication under which these joints operate, a synthetic lubricant was
      used in all these tests. Friction tests were carried out to assess the
      lubrication of four PU bearing materials. Corethane 80A was the preferred
      material and was subjected to subsequent testing. Friction tests conducted on
      acetabular cups, manufactured using Corethane 80A articulating against standard,
      commercially available femoral heads, demonstrated friction factors approaching
      those for full-fluid-film lubrication with only approximately 1 per cent asperity
      contact. As the joint produces these low friction factors within less than half a
      walking cycle after prolonged periods of loading, start-up friction was not
      considered to be a critical factor. Cups performed well across the full range of
      femoral head sizes, but a number of samples manufactured with reduced radial
      clearances performed with higher than expected friction. This was caused by the
      femoral head being gripped around the equator by the low clearance cup. To avoid
      this, the cup design was modified by increasing the flare at the rim. In addition
      to this the radial clearance was increased. As the material is incompressible, a
      radial clearance of 0.08 mm was too small for a cup diameter of 32 mm. A
      clearance of between 0.10 and 0.25 mm produced a performance approaching full
      fluid-film lubrication. This series of tests acted as a step towards the
      optimization of the design of these joints, which has now led to an in vivo ovine
      model.

PMID- 16898217
TI  - The role of the surface amorphous layer of articular cartilage in joint
      lubrication.
AB  - Articular cartilage is a complex soft tissue that performs multiple functions in
      the joint. In particular, the amorphous layer that covers the surface of
      articular cartilage is thought to play some role in lubrication. This study aimed
      to characterize the surface amorphous layer (SAL) using a variety of techniques,
      including environmental scanning electron microscopy, transmission electron
      microscopy, white light interferometry, and biochemical analysis of its
      composition. Friction tests were conducted to investigate the role of the SAL in
      lubrication. A protocol to remove successfully the SAL without damaging the
      underlying cartilage was developed and the material removed from healthy
      cartilage was found to contain approximately equal quantities of
      glycosaminoglycan (GAG), protein, and lipid. Cartilage-on-cartilage friction
      tests were conducted on fresh, healthy cartilage with and without the SAL, under
      both dynamic and static operating conditions. Removal of the SAL was not found to
      change the friction coefficient. However, subsequent staining of specimens
      indicated that the SAL had replenished during the test following loading. The
      replenished SAL was characterized and found to contain lipids and sulphated GAGs
      with undetectable protein. This study revealed experimental evidence of surface
      layer replenishment in articular cartilage. It was postulated that the surface
      layer regeneration mechanism was purely mechanical and associated with movement
      of GAGs and lipids through the cartilage matrix during deformation, since the
      experimental set-up did not contain any means of biochemical activation.

PMID- 16898219
TI  - Numerical predictions of the thermal behaviour and resultant effects of grouting
      cements while setting prosthetic components in bone.
AB  - Acrylic cements are commonly used to attach prosthetic components in joint
      replacement surgery. The cements set in short periods of time by a complex
      polymerization of initially liquid monomer compounds into solid structures with
      accompanying significant heat release. Two main problems arise from this form of
      fixation: the first is the potential damage caused by the temperature excursion,
      and the second is incomplete reaction leaving active monomer compounds, which can
      potentially be slowly released into the patient. This paper presents a numerical
      model predicting the temperature-time history in an idealized prosthetic-cement
      bone system. Using polymerization kinetics equations from the literature, the
      degree of polymerization is predicted, which is found to be very dependent on the
      thermal history of the setting process. Using medical literature, predictions for
      the degree of thermal bone necrosis are also made. The model is used to identify
      the critical parameters controlling thermal and unreacted monomer distributions.

PMID- 16898218
TI  - Increased total knee arthroplasty ultra-high molecular weight polyethylene wear
      using a clinically relevant hyaluronic acid simulator lubricant.
AB  - In this study, osteoarthritic and periprosthetic synovial fluid samples were
      rheologically and biochemically compared to develop a hyaluronic acid (HA)
      supplemented bovine serum (BS) lubricant that mimicked the properties of human
      joint synovial fluid. The effect of this BS + HA lubricant (50 per cent bovine
      calf serum + 1.5 g/l HA) on the wear rate of ultra-high molecular weight
      polyethylene (UHMWPE) during a total knee replacement wear test was then
      investigated. In conjunction with biochemical similarities, the rheological
      analysis showed that the BS + HA lubricant viscosity was not statistically
      different to aspirated total knee arthroplasty (TKA) revision joint fluid
      viscosity over a range of physiologic shear rates. Gravimetric results at 5
      million wear testing cycles showed that the BS + HA lubricant produced an average
      of 6.88 times more UHMWPE wear than 50 per cent bovine serum lubricant alone. The
      BS + HA lubricated CoCr femoral component surfaces revealed pitting and surface
      roughening that was not observed using standard bovine serum only lubricants, but
      that was similar to the metallic surface corrosion observed on in vivo CoCr
      femoral component retrievals. These findings support the hypothesis that the
      addition of HA to simulator lubricant is capable of producing CoCr femoral
      component surface damage similar to that observed in vivo.

PMID- 16898220
TI  - The clinical repair of teeth using direct filling materials: engineering
      considerations.
AB  - This paper reviews the way in which teeth damaged by caries may be repaired
      clinically. The mechanical effects of caries are described, as are the materials
      available to repair the damage caused by this disease. Studies are reported which
      have shown that caries reduces the compressive strength of the tooth to less than
      50 per cent of its original value and that, by use of appropriate materials and
      placement techniques, this can be restored to some 80 per cent of this value.
      However, very few studies have been carried out which view tooth repair from an
      engineering perspective. Instead, emphasis is placed on determining clinical
      durability of repairs. This is related to repair strength but brings in other
      factors, such as the oral hygiene of the patient. Despite this complication,
      durability studies show that modern restorative materials perform well under
      clinical conditions, from which it may be concluded that the repair process
      allows a structure to be fabricated that is essentially sound from an engineering
      viewpoint, even if inferior to the original tooth structure provided by nature.

PMID- 16898221
TI  - Explaining left ventricular pressure dynamics in terms of LV passive and active
      elastances.
AB  - There has been much characterization of the heart as a pump by means of models
      based on elastance and compliance. The present paper puts forward the new concept
      of time-varying passive and active elastance. The biomechanical basis of cyclic
      elastances of the left ventricle (LV) is presented. Elastance is defined in terms
      of the relationship between ventricular pressure and volume as dP = EdV+ VdE,
      where E includes passive elastance, Ep, and active elastance, Ea. By
      incorporating this concept in LV models to simulate diastolic (filling) and
      systolic phases, a time-varying expression has been obtained for Ea, and an LV
      volume dependent expression has been obtained for Ep. It is proposed to use these
      two elastances Ea and Ep to represent the intrinsic LV properties. The active
      elastance, Ea, can be used to characterize the LV contractile state and
      represents LV pressure variation due to LV volume variation (such as during the
      filling and ejection phases). The passive elastance, Ep, can serve as a measure
      of LV resistance to filling. Furthermore, it has been demonstrated how the LV
      pressure dynamics (and LV pressure response to LV volume) can be explained in
      terms of Ea and Ep.

PMID- 16898222
TI  - Neural transplantation in Huntington's disease: the NEST-UK donor tissue
      microbiological screening program and review of the literature.
AB  - Neural transplantation of human fetal tissue for Huntington's disease (HD) is now
      entering the clinical arena. The safety of the procedure has now been
      demonstrated in a number of studies, although the efficacy of such an approach is
      still being investigated. Stringent but practicable screening of the donor tissue
      for potential pathogens is an essential prerequisite for successful
      implementation of any novel transplant program that uses human fetal tissue. In
      this article we summarize the UK-NEST protocol for the screening of human fetal
      tissue being grafted to patients with mild to moderate HD. We describe the
      results of microbiological screening of 87 potential tissue donors in a pilot
      study, and of the first four donor-recipient patients included in the UK-NEST
      series. The rationale for the adoption and interpretation of the various tests is
      described and our methodology is compared with those previously used by other
      centers. This article therefore presents a comprehensive, logical yet pragmatic
      screening program that could be employed in any clinical studies that use human
      fetal tissue for neurotransplantation.

PMID- 16898223
TI  - Chemokines and their receptors in islet allograft rejection and as targets for
      tolerance induction.
AB  - Graft rejection is a major barrier to successful outcome of transplantation
      surgery. Islet transplantation introduces insulin secreting tissue into type 1
      diabetes mellitus recipients, relieving patients from exogenous insulin
      injection. However, insulitis of grafted tissue and allograft rejection prevent
      long-term insulin independence. Leukocyte trafficking is necessary for the launch
      of successful immune responses to pathogen or allograft. Chemokines, small
      chemotactic cytokines, direct the migration of leukocytes through their
      interaction with chemokine receptors found on cell surfaces of immune cells.
      Unique receptor expression of leukocytes, and the specificity of chemokine
      secretion during various states of immune response, suggest that the
      extracellular chemokine milieu specifically homes certain leukocyte subsets.
      Thus, only those leukocytes required for the current immune task are attracted to
      the inflammatory site. Chemokine blockade, using antagonists and monoclonal
      antibodies directed against chemokine receptors, is an emerging and specific
      immunosuppressive strategy. Importantly, chemokine blockade may potentiate
      tolerance induction regimens to be used following transplantation surgery, and
      prevent the need for life-long immunosuppression of islet transplant recipients.
      Here, the role for chemokine blockade in islet transplant rejection and tolerance
      is reviewed.

PMID- 16898224
TI  - Porcine islet graft function is affected by pretreatment with a caspase-3
      inhibitor.
AB  - During the isolation procedure and after transplantation islets are subjected to
      numerous variables associated with the induction of apoptosis. The present study
      investigated the effect of transient pretreatment with caspase inhibitors on
      function and survival of transplanted pig islets. Isolated porcine islets (3000
      IEQ) were incubated overnight in 200 microM of the caspase-3 inhibitor DEVD-CMK
      prior to transplantation into diabetic nude mice. Glucose-stimulated insulin
      release of pretreated islets was assessed during static incubation. DEVD-CMK
      successfully prevented the expression of capase-3 and DFF as demonstrated in heat
      shocked pig islets. Nevertheless, transient pretreatment of freshly isolated pig
      islets with DEVD-CMK resulted in a significantly decreased final graft function
      of 50.0% (n = 16) compared to 85.7% (n = 14) in control islets (p < 0.05).
      Glucose-stimulated insulin release of porcine islets (n = 6) was not
      significantly effected by overnight culture with DEVD-CMK. Morphological
      assessment revealed that this caspase-3 inhibitor significantly increased the
      percentage of necrosis to a small, but nevertheless significant, extent in
      comparison to control islets (p < 0.05). The study demonstrates that short-time
      pretreatment with the caspase-3 inhibitor DEVD-CMK reduces the capacity of
      transplanted porcine islets to restore normoglycemia in diabetic nude mice.

PMID- 16898225
TI  - Survival and function of transplanted islet cells on an in vivo, vascularized
      tissue engineering platform in the rat: A pilot study.
AB  - As in vivo tissue engineering of complex tissues and organs progresses, there is
      a need for an independently vascularized, alterable, and recoverable model.
      Current models of islet cell transplantation (release into the portal venous
      system, placement under the renal capsule, and microencapsulation) lack these
      qualities. We have developed a model of angiogenesis and spontaneous tissue
      generation in the rat that lends itself as a potential platform for tissue
      engineering. In this experiment, we examined the effectiveness of such a model in
      addressing some of the shortcomings of endocrine pancreatic transplantation. An
      arteriovenous loop was created in the groins of five adult inbred Sprague-Dawley
      rats, and placed within polycarbonate chambers. Isolated pancreatic islet cell
      clusters were placed within the chambers, suspended in a matrix of Matrigel. The
      chambers were recovered at 3 weeks, and the newly generated tissue was processed
      for histologic and immunohistochemical analysis. By 3 weeks, spontaneous
      generation of angiogenesis and collagen matrix and deposition of a collagen
      matrix was observed. Surviving islet cells were identified by histology and their
      viability was confirmed via immunohistochemistry for insulin and glucagon. This
      study demonstrates the ability to maintain viability and functionality of
      transplanted islet cells on a tissue-engineered platform with an independent
      vascular supply. The model provides the ability to alter the graft environment
      via matrix substitution, cellular coculture, and administration of growth
      factors. The transplanted tissues are recoverable without animal sacrifice and
      are microsurgically transferable. This model may provide an in vivo culture
      platform for the study of islet transplantation.

PMID- 16898226
TI  - Maintenance of mouse, rat, and pig pancreatic islet functions by coculture with
      human islet-derived fibroblasts.
AB  - Development of an efficient preculture system of islets is ideal. Toward that
      goal, we constructed a human pancreatic islet-derived fibroblast cell line MNNK-1
      for a source as a coculture system for freshly isolated islets to maintain islet
      functions. Human pancreatic islet cells were nucleofected with a plasmid vector
      pYK-1 expressing simian virus 40 large T antigen gene (SV40T) and hygromycin
      resistance gene (HygroR). One of the transduced cell lines, MNNK-1, was
      established and served as a feeder cell in the coculture for freshly isolated
      mouse, rat, and pig islets. Morphology, viability, and glucose-responding insulin
      secretion were analyzed in the coculture system. MNNK-1 cells were
      morphologically spindle shaped and were negative for pancreatic endocrine
      markers. MNNK-1 cells were positive for alpha-smooth muscle actin and collagen
      type I and produced fibroblast growth factor. Coculture of the mouse, rat, and
      pig islets with MNNK-1 cells maintained their viability and insulin secretion
      with glucose responsiveness. A human pancreatic islet-derived fibroblast cell
      line MNNK-1 was established. MNNK-1 cells were a useful means for maintaining
      morphology and insulin secretion of islets in the coculture system.

PMID- 16898228
TI  - The development and characterization of an HEK293-derived cell line for use in an
      intratumoral cytokine delivery system.
AB  - As part of ongoing work to develop a method of cytokine delivery for use as an
      intratumoral depot, we noted that HEK293 cells, encapsulated in alginate, died
      within 24-48 h after in vivo, intratumoral implantation. We hypothesized that the
      highly hypoxic and acidic conditions found inside the tumor was the cause of the
      cells' premature demise. Therefore, we set out to develop a cell line, derived
      from HEK293, that would survive these hostile conditions. The HEK293 line was
      selected in 0.3-0.5% oxygen conditions over several weeks, followed by a further
      6-week period of culture in alternating hypoxic and normoxic conditions. The most
      rapidly growing clones were selected and grown in normoxic conditions for several
      weeks to ensure their stability. The clones were then compared to the original
      line in terms of cell proliferation in normoxia and hypoxia, colony-forming
      efficiency, and morphological characteristics. The resulting line was able to
      proliferate in the harshest of conditions and continues to release its biological
      payload after alginate microencapsulation.

PMID- 16898227
TI  - Differentiation of human embryonic stem cells to hepatocytes using deleted
      variant of HGF and poly-amino-urethane-coated nonwoven polytetrafluoroethylene
      fabric.
AB  - Human embryonic stem (hES) cells have recently been studied as an attractive
      source for the development of a bioartificial liver (BAL). Here we evaluate the
      differentiation capacity of hES cells into hepatocytes. hES cells were subjected
      to suspension culture for 5 days, and then cultured onto poly-amino-urethane
      (PAU)-coated, nonwoven polytetrafluoroethylene (PTFE) fabric in the presence of
      fibroblast growth factor-2 (bFGF) (100 ng/ml) for 3 days, then with deleted
      variant of hepatocyte growth factor (dHGF) (100 ng/ml) and 1% dimethyl sulfoxide
      (DMSO) for 8 days, and finally with dexamethasone (10(-7) M) for 3 days. The hES
      cells showed gene expression of albumin in a time-dependent manner of the hepatic
      differentiation process. The resultant hES-derived hepatocytes metabolized the
      loaded ammonia and lidocaine at 7.8% and 23.6%, respectively. A million of such
      hepatocytes produced albumin and urea at 351.2 ng and urea at 7.0 microg.
      Scanning electron microscopy showed good attachment of the cells on the surface
      of the PTFE fabric and well-developed glycogen rosettes and Gap junction. In the
      present work we have demonstrated the efficient differentiation of hES cells to
      functional hepatocytes. The findings are useful to develop a BAL.

PMID- 16898229
TI  - Short-term heart retention and distribution of intramyocardial delivered
      mesenchymal cells within necrotic or intact myocardium.
AB  - Cell therapy with bone marrow mesenchymal stem cells (BMSCs) is a new strategy
      for treating ischemic heart failure, but data concerning the distribution and
      retention of transplanted cells remain poor. We investigated the short-term
      myocardial retention of BMSCs when these cells are directly injected within
      necrotic or intact myocardium. 111Indium-oxine-labeled autologous BMSCs were
      injected within either 1-month-old infarction (n = 6) or normal myocardium (n =
      6) from rats. Serial in vivo pinhole scintigraphy was scheduled during 1 week in
      order to track the implanted cells. The myocardial retention of BMSCs was
      definitely higher in myocardial infarction than in normal myocardial area
      (estimated percent retention at 2 h: 63 +/- 3% vs. 25 +/- 4%, p < 0.001) and the
      estimated cardiac retention values were unchanged in both groups along the 7 days
      of follow-up. On heart sections at day 7, labeled BMSCs were still around the
      injection site and appeared confined to the scarred tissue corresponding either
      to the infarct area or to the myocardium damaged by needle insertion. BMSCs have
      a higher retention when they are injected in necrotic than in normal myocardial
      areas and these cells appear to stay around the injection site for at least a 7
      day period.

PMID- 16898230
TI  - Survival of microencapsulated islets at 400 days posttransplantation in the
      omental pouch of NOD mice.
AB  - The long-term durability of agarose microencapsulated islets against autoimmunity
      was evaluated in NOD mice. Islets were isolated from 6-8-week-old prediabetic
      male NOD mice and microencapsulated in 5% agarose hydrogel. Microencapsulated or
      nonencapsulated islets were transplanted into the omental pouch of spontaneously
      diabetic NOD mice. Although the diabetic NOD mice that received nonencapsulated
      islets experienced a temporary reversal of their hyperglycemic condition, all 10
      of these mice returned to hyperglycemia within 3 weeks. In contrast, 9 of 10 mice
      transplanted with microencapsulated islets maintained normoglycemia for more than
      100 days. Islet grafts were removed at 100, 150, 200, 300, and 400 days
      posttransplantation. A prompt return to hyperglycemia was observed in the mice
      after graft removal, indicating that the encapsulated islet grafts were
      responsible for maintaining euglycemia. Histological examination revealed viable
      islets in the capsules at all time points of graft removal. In addition, beta
      cells within the capsules remained well granulated as revealed by the
      immunohistochemical detection of insulin. No immune cells were detected inside
      the microcapsules and no morphological irregularities of the microcapsules were
      observed at any time point, suggesting that the microcapsules successfully
      protected the islets from cellular immunity. Sufficient vascularization was
      evident close to the microcapsules. Considerable numbers of islets showed central
      necrosis at 400 days posttransplantation, although the necrotic islets made up
      only a small percentage of the islet grafts. Islets with central necrosis also
      showed abundant insulin production throughout the entire islets, except for the
      necrotic part. These results demonstrate the long-term durability of agarose
      microcapsules against autoimmunity in a syngeneic islet transplantation model in
      NOD mice.

PMID- 16898231
TI  - Occupational health - a very important component of public health.

PMID- 16898232
TI  - Changing in the face of change.

PMID- 16898233
TI  - Beliefs and practices in the assessment of workplace pollutants.
AB  - OBJECTIVES: A survey was undertaken among Swiss occupational hygienists and other
      professionals to identify the different exposure assessment methods used, the
      contextual parameters observed and the uses, difficulties and possible
      developments of exposure models for field application. METHODS: A questionnaire
      was mailed to 121 occupational hygienists, all members of the Swiss Occupational
      Hygiene Society. A shorter questionnaire was also sent to registered occupational
      physicians and selected safety specialists. Descriptive statistics and
      multivariate analyses were performed. RESULTS: The response rate for occupational
      hygienists was 60%. The so-called expert judgement appeared to be the most widely
      used method, but its efficiency and reliability were both judged with very low
      scores. Long-term sampling was perceived as the most efficient and reliable
      method. Various determinants of exposure, such as emission rate and work
      activity, were often considered important, even though they were not included in
      the exposure assessment processes. Near field local phenomena determinants were
      also judged important for operator exposure estimation. CONCLUSION: Exposure
      models should be improved to integrate factors which are more easily accessible
      to practitioners. Descriptors of emission and local phenomena should also be
      included.

PMID- 16898234
TI  - Effects of a physical exercise intervention on employees'perceptions quality of
      life: a randomized controlled trial.
AB  - OBJECTIVES: To determine the effects of an exercise intervention in workplace
      health promotion, WHO multidimensional quality of life was chosen as the main
      outcome variable. Secondary outcomes were different physical fitness indicators.
      METHODS: 110 employees (83 male, 27 female, modus age group 36-45 years)
      volunteered to participate and were randomly allocated to intervention (n = 52)
      or control group (n = 58). Intervention subjects exercised 13 weeks, at leisure
      time, in off-worksite training facilities. Outcome measures were assessed before
      and after the intervention, and at 3 month follow-up. RESULTS: Significant
      training effects resulted for overall perception of quality of life, and for
      psychological and physical health sub-domains. Physical strength indicators
      improved significantly as well, with these changes being independent from
      psychological health benefits. At follow-up, elevated psychological scores held
      steady only for those who continued to exercise on their own. DISCUSSION: This
      intervention had impact on important health indicators. Since it was arranged on
      top of a "real world" occupational health promotion program, the observed
      findings should even more encourage employers to invest in their employees'
      health.

PMID- 16898235
TI  - Responders and non-responders in a study on medical end-of-life decisions in
      Denmark, the Netherlands, Sweden and Switzerland.
AB  - OBJECTIVES: To determine the direction and magnitude of participation bias in end
      of-life research. METHODS: Within the framework of a European survey on medical
      end-of-life decisions, a non-response study was conducted among physicians in
      Denmark, the Netherlands, Sweden and Switzerland. People were asked about their
      attitudes and experiences in the area of medial end-of-life decision. The
      response rates ranged from 12.8% (Netherlands) to 39.4% (Switzerland). The
      responders (n = 5403) and the non-responders (n = 866) were compared regarding
      socio-demographic characteristics, experiences with terminal patients and
      agreement with attitudes towards "end-of-life decisions". The reasons for non
      participation to the study were analyzed. RESULTS: Non-response did not cause
      socio-demographic distortion, but non-responders had statistically significantly
      fewer terminal patients than responders. Agreement rates were statistically
      significantly higher among responders than among non-responders for euthanasia,
      non-treatment decision and life-preserving statements. Neutral answers were
      statistically significantly more frequent among non-responders than among
      responders for life-preserving and euthanasia statements. The most commonly
      mentioned reason for non-participation was "lack of time". CONCLUSION: Non
      participation does cause an overestimation of proponents of life-shortening, as
      well as of life-preserving end-of-life decisions. Non-responders more often have
      ambiguous attitudes towards end-of-life decisions than responders.

PMID- 16898237
TI  - Beware the pitfalls of ill-placed questions - revisiting questionnaire ordering.

PMID- 16898236
TI  - Missing data due to a 'checklist misconception-effect'.
AB  - OBJECTIVES: To analyze the extent and relevance of a postulated "checklist
      misconception-effect" (a specific response pattern characterized by symptom-free
      persons not checking the "not at all"-category). METHODS: Our data is derived
      from a survey of blue collar workers (n = 228) who previously had filed in
      applications for medical rehabilitation benefits. We defined the "checklist
      misconception-effect" by the following response pattern: (1) at least one missing
      value and (2) at least one valid item response and (3) no 'not at all' responses.
      RESULTS: 75% of the responders had complete data, 16.2% a postulated 'checklist
      misconception-effect'. Substantial co-variations with socio-demographic
      characteristics or health status indicators could not be found. Additional
      imputation of missing values under the assumption of a "checklist misconception
      effect" led to a reduction of missing data in the somatisation-subscale score
      from 12.3% to 0.4% compared to a simple manual-based calculation. Correlation
      with various external criteria (general health perception, level of functioning,
      depression) remained unchanged. CONCLUSIONS: Ignoring the "checklist
      misconception-effect" would overestimate symptom load. However, the validity of
      this effect has still to be proven in methodological studies.

PMID- 16898239
TI  - The Georgian adolescent health survey: methodological and strategic issues.
AB  - OBJECTIVES: To conduct a national survey on adolescent health and lifestyles in
      Georgia and to thus set up a database on adolescent. METHODS: A two-stage cluster
      sample of around 8000-10000 in-school 15-18 years adolescents are being reached
      through a random selection of classes in Georgia. The sample has been stratified
      by age, region, type of school and language. A self-administered questionnaire of
      87 questions has been developed and translated into the four main languages used
      in Georgia. RESULTS: Up to June 2004, the researchers have reached 511 classes
      (9306 pupils). In total, 8039 questionnaires have been considered valid. The main
      concerns encountered for this survey are linked with acceptance of the survey,
      cross-cultural issues, political and strategic problems as well as inadequate
      physical environmental support. CONCLUSION: Despite Georgia's unfavourable
      economical and political situation, it has been possible to run a national survey
      on the health of adolescents, according to the usual standards used in the field.
      This survey should allow for 1) the identification of priorities in the field of
      health care and health promotion 2) the monitoring of adolescent health in the
      future.

PMID- 16898240
TI  - [Results and prospects of activities performed by Research Institute of complex
      problems of hygiene and occupational diseases].

PMID- 16898238
TI  - Self-rated health and health damaging behaviour among young women in Hungary in
      connection with family background.
AB  - OBJECTIVES: To describe the relationship of subjective health and harmful
      lifestyle with familial risk factors, such as low parental educational level,
      parental psychiatric disorder reported by their offspring, alcohol use, and
      divorce. METHODS: 3615 hungarian women aged 15-24 in 1998. The questionnaire
      addressed socio-economic factors, physical and mental health, and health damaging
      behaviours. RESULTS: Low self-rated health (OR: 2.32; Cl: 1.54-3.47; p < 0.001)
      or at least five health complaints (OR: 2.09; CI: 1.68-2.60; p < 0.001) were
      significantly more common among women with reported parental psychiatric
      disorder. Drug use (OR: 2.35; CI: 1.86-2.98; p < 0.001) and regular or excessive
      alcohol consumption (OR: 1.86; CI: 1.46-2.37) was in strongest association with
      parental high education. CONCLUSIONS: Family related social problems, especially
      reported parental psychiatric disorders, regular alcohol consumption, and
      educational level, are important factors to be taken into account when planning
      specific interventions for young women.

PMID- 16898241
TI  - [Immune genetic markers of anthracosilicosis].
AB  - Studies of ABO, Rh, MN, rho, Lewis blood groups in coal miners suffering from
      anthracosilicosis and in reference healthy individuals proved that MM phenotypes
      are predisposed to anthracosilicosis and MN phenotypes could be resistant to the
      disease. These results could be valuable for prevention of this occupational
      disease among coal industry workers.

PMID- 16898242
TI  - [Monitoring and controlling risk of occupational morbidity on aluminium plant].
AB  - The authors specified and introduced a system monitoring occupational diseases
      (fluor intoxication) on aluminium plant. Clinical examination of workers in
      groups with various risk levels proved design values to be reliable. Suggestions
      included main principles of risk management to decrease probability of
      occupational diseases in aluminium production.

PMID- 16898243
TI  - [Evaluating risk of morbidity among workers of coal open-cast mines in Kuzbass].
AB  - Work conditions on open-cast minest of Kuzbass include complex of unfavorable
      natural climate, mining technical occupational factors (microclimate, industrial
      noise, vibration, aerosols, toxic chemicals, hardiness and intensity of work).
      According to those occupational factors, the authors calculated risks of
      morbidity and safe length of service.

PMID- 16898245
TI  - [Comparison of clinical signs in various severity grades of vibration disease].
AB  - Examination covered 288 coal miners with vibration disease varying in severity
      grade. Findings were frequent angiodystonic syndrome (97-100%), upper limbs
      periarthrosis and arthrosis, frequent association with cervical, lumbar and
      sacral radiculopathy with mutual deterioration.

PMID- 16898244
TI  - [Serum biochemistry data in association of atherosclerosis with pulmonary dust
      diseases].
AB  - The authors studied prevalence of atherosclerosis, serum levels of lipids and
      homocysteine in coal miners suffering from pulmonary dust diseases. More marked
      hyperlipidemia and hyperhomocysteinemia are associated with combination of
      atherosclerosis and pulmonary dust diseases. Respiratory failure as a
      complication of pulmonary dust diseases promotes hyperlipidemia.

PMID- 16898246
TI  - [Health state of Altai area residents].
AB  - High level of somaticas well as psychic morbidity results in increasing general
      and early mortality, mostly in men. Depopulation grows and over the nearest 20
      years will result in significant age disproportion, higher overall
      demographicload on able-bodied population and will complicate qualitative and
      quantitative problems of working potential of Altai area.

PMID- 16898248
TI  - [Compression neuropathy of upper limbs in miners].
AB  - The authors analyzed prevalence of individual types of upper limb compression
      neuropathy in miners of coal and iron-ore mines. Medical examination covered main
      mining occupations exposed to suchhazards as local vibration, cooling
      microclimate, functional overstrain. Some types of compression neuropathies
      appeared to depend on duration of exposure to the hazards and on the occupation
      hands disease stage.

PMID- 16898247
TI  - [Experimental development of atherosclerosis].
AB  - The article deals with influence of coal rock dust on biochemical and immunologic
      serum parameters in experiment. Findings are that 3-week impact of coal rock dust
      (22 mg/m3) causes stress reaction and metabolism activation. Double increase of
      the duration and the concentration induces hypoxia component, immune deficiency
      elements and inflammation start.

PMID- 16898250
TI  - [Evaluating health risk for workers due to polluted air in auxiliary workshops of
      heat power stations].
AB  - The authors evaluated health risk for workers of auxiliary workshops in heat
      power stations by workplace air,caused by workplace air pollution with solid
      particles, nitrogen dioxide, sulfur dioxide, phenol, carbon oxide, benzpyrene.
      This evaluation was a part of longstanding research designing measures to
      optimize work conditions. Kuznetsk heat power station served as an example to
      calculate mean air concentrations of chemicals, yearly individual risk of chronic
      intoxication, to determine contribution of each individual chemical into the
      overall risk, to assess individual risk due to benzpyrene inhalation.

PMID- 16898249
TI  - [Prevalence of vertebrogenic diseases].
AB  - The authors studied prevalence of bone congenital malformations including
      congenital vertebral canal stenosis, of acquired vertebral canal stenosis due to
      intervertebral disc prolapse, yellow ligament hypertrophy, and combinations of
      those two in patients with occupational and general vertebral diseases.

PMID- 16898251
TI  - [Improving clinical examination of workers in metallurgic enterprises].
AB  - The authors justify necessity to improve system of clinical examination of
      workers, within "Health" priority national project, present suggestions on
      realization of specific measures in metallurgic enterprises.

PMID- 16898252
TI  - [Using nutriceutics for occupational fluorosis prevention].
AB  - The article deals with pathogenesis of occupational fluorosis. Clinical studies
      demonstrated changes in bone mineral density among workers with 15-20 years of
      service. Experimental studies proved that occupational fluorosis is associated
      withcalcium dysbalance,bone tissue resorption and calcium washout. Nutriceutics
      ("Zolotoi shar", "Korallovy kalcii") in occupational fluorosis play preventive
      role.

PMID- 16898253
TI  - Practical management of medication-overuse headache.
AB  - Epidemiological studies suggest that medication-overuse as defined by the
      International Headache Society is extremely common in patients with chronic daily
      headache. If all medication-overuse produces medication-overuse headache (MOH) in
      headache patients, it would be the third most frequent form of headache, after
      tension-type headache and migraine. Treatment of MOH is hindered by the absence
      of placebo-controlled, double-blind, randomised clinical trials. Nevertheless,
      several headache centers worldwide have developed expertise in the treatment of
      this syndrome, and have been quite successful. Here, we summarize available data
      on MOH, including clinical features, drugs used in withdrawal, as well as
      withdrawal strategies that have been described in the literature. We also include
      a detailed description of an in-patient and out-patient withdrawal procedure,
      reflecting personal experience and opinion of the authors.

PMID- 16898255
TI  - Neuropathy and Fabry disease: pathogenesis and enzyme replacement therapy.
AB  - The neurological manifestations of Fabry disease include both peripheral and
      central nervous system involvement caused by a deficiency of alpha-galactosidase
      A and accumulation of alpha-D-galactosyl moieties, particularly
      globotriosylceramide accumulation (Gb3). These are found in Schwann cells and
      dorsal root ganglia together with deposits in central nervous system neurons.
      Involvement of the peripheral nervous system affect mainly small Adelta and C
      fibers and are likely causally related to the altered autonomic function and
      neuropathic pain found in this disorder. Other related abnormalities to be
      discussed are hypohidrosis and other abnormalities attributed to autonomic
      nervous system dysfunction. The function of the peripheral nervous system is
      somewhat improved by ERT with reduction in neuropathic pain and an improvement of
      the detection threshold for cold and warm sensation in the hand and foot.
      Improvement in sweating and heat tolerance is also noted following ERT. Despite
      those positive results, ERT does not normalize the function of the peripheral
      nervous system.

PMID- 16898256
TI  - Autosomal disorders of mitochondrial DNA maintenance.
AB  - Mitochondrial DNA (mtDNA) is maternally inherited. After birth, secondary mtDNA
      defects can arise. MtDNA depletion is a reduction in the amount of mtDNA in
      particular tissues. Multiple deletions of mtDNA accumulate as somatic mutations
      in mainly postmitotic tissues. These disorders of mtDNA maintenance frequently
      show Mendelian inheritance. Positional cloning has identified several genes
      involved in the control of mtDNA stability. Recessive mutations in the genes
      ECGF1, dGK, TK2, SUCLA2 and POLG cause mtDNA depletion syndromes (MDS).
      Generally, MDS has infantile onset tissue specific features. Mutations in the
      genes ECGF1, ANT1, C10orf2 and POLG are associated with multiple mtDNA deletions.
      The nature of these mutations is dominant in ANT1, C10orf2 and POLG and recessive
      in ECGF1, C10orf2 and POLG. Mutations in these genes frequently cause progressive
      external ophthalmoplegia (PEO). However clinical heterogeneity results in
      different neurological syndromes with considerable overlap. The most common
      features are PEO, neuropathy, myopathy, ataxia, epilepsy and hepatopathy.

PMID- 16898254
TI  - The epileptic syndromes with continuous spikes and waves during slow sleep:
      definition and management guidelines.
AB  - The authors propose to define the epileptic syndromes with continuous spikes and
      waves during slow sleep (CSWS) as a cognitive or behavioral impairment acquired
      during childhood, associated with a strong activation of the interictal
      epileptiform discharges during NREM sleep--whatever focal or generalized--and not
      related to another factor than the presence of CSWS. The type of syndrome will be
      defined according to the neurological and neuropsychological deficit. These
      syndromes have to be classified among the localization-related epileptic
      syndromes. Some cases are idiopathic and others are symptomatic. Guidelines for
      work-up and treatment are proposed.

PMID- 16898257
TI  - Nerve conduction studies in polyneuropathy: practical physiology and patterns of
      abnormality.
AB  - Nerve conduction studies are an essential part of the work-up of peripheral
      neuropathies. Many neuropathic syndromes can be suspected on clinical grounds,
      but optimal use of nerve conduction study techniques (in combination with needle
      electromyography) allows diagnostic classification and is therefore crucial to
      understanding and separation of neuropathies. Multifocal motor neuropathy, for
      example, may clinically present as ALS. Detection of evidence of demyelination
      (conduction blocks) leads to the correct diagnosis and to proper treatment. Nerve
      conduction studies provide essential information on (1) the spatial pattern of
      neuropathy, (2) the pattern of abnormalities distinguishing between primarily
      axonal and demyelinating pathology, and (3) the severity of neuropathic damage.
      This information is very comprehensive since many nerves and long segments of
      individual nerves can be sampled. Moreover the information is extremely detailed
      to the extent that the cellular pathology of a patient's neuropathy is usually
      defined best by physiological testing rather than by biopsy. Neuropathies can be
      generalized, focal, or multifocal; they can be symmetric or asymmetric; they can
      be distally predominant or proximal and distal. Primarily axonal neuropathies
      mainly affect sensory nerve and compound muscle action potential amplitudes,
      whereas demyelinating neuropathies lead to slowing of nerve conductions, and to
      increased temporal dispersion or conduction block. Usually, the pattern of
      demyelination allows to distinguish hereditary (uniform demyelination) from
      acquired (segmental demyelination) neuropathies. Electrodiagnostic criteria for
      primary demyelination are helpful to identify acquired demyelinating
      neuropathies.

PMID- 16898258
TI  - Pompe disease (glycogen storage disease type II): clinical features and enzyme
      replacement therapy.
AB  - Pompe disease (glycogen storage disease type II, acid maltase deficiency) is a
      progressive metabolic myopathy caused by deficiency of the lysosomal enzyme acid
      alpha-glucosidase. This leads to an accumulation of glycogen in various tissues
      of the body, most notably in skeletal muscle. The disease has an autosomal
      recessive inheritance with a predicted frequency of 1 :40.000. Pompe disease is a
      continuous spectrum but for clinical practice different subtypes are recognized.
      The classic infantile form of the disease occurs in infants (shortly after birth)
      and is characterized by generalized hypotonia, failure to thrive, and
      cardiorespiratory failure. Patients usually die within the first year of life.
      The non-classic or late-onset form of the disease may occur at any age in
      childhood or adulthood. It presents predominantly as a slowly progressive
      proximal myopathy, with or without respiratory failure. Enzyme replacement
      therapy (ERT) is under study as treatment for the disease. The first results with
      recombinant human alpha-glucosidase are promising and a registered therapy seems
      near. Beneficial effects of ERT have been reported both in patients with the
      classic infantile form as well as in patients with the non-classic or late-onset
      form of the disease. The best therapeutic results are achieved when ERT is
      started early in the course of symptom development and before irreversible
      muscular damage has occurred. Detailed knowledge about the natural course of the
      disease becomes more and more essential to determine the indication and timing of
      treatment.

PMID- 16898259
TI  - Central nervous system metastases of pulmonary adenocarcinoma mimicking
      neurofibromatosis type 2.
AB  - We report a case of a 51-year-old man presenting with rapidly progressive
      unilateral tinnitus, hearing loss and imbalance. Neuroimaging revealed bilateral
      VIIIth cranial nerve masses and multiple cerebral and spinal cord lesions that
      were interpreted as being acoustic schwannomas and multiple meningeomas. An
      initial tentative diagnosis of neurofibromatosis type 2 (NF2) was made. Both
      clinical and radiological evolution were atypical for NF2 and the initial
      diagnosis of NF2 was questioned. Additional technical investigations demonstrated
      a pulmonary adenocarcinoma. Postmortem examination confirmed that this patient
      had multiple central nervous system metastases of a primary pulmonary
      adenocarcinoma, presenting clinically and neuroradiologically as a probable
      neurofibromatosis type 2. Clinicians should be aware of the rare possibility of
      central nervous system metastases mimicking NF2.

PMID- 16898260
TI  - Neuromodulation with levetiracetam and vagus nerve stimulation in experimental
      animal models of epilepsy.
AB  - Epilepsy is a neurological disorder consisting of recurrent seizures, resulting
      from excessive, uncontrolled electrical activity in the brain. Epilepsy treatment
      is successful in the majority of the cases; however; still one third of the
      epilepsy patients are refractory to treatment. Besides the ongoing research on
      the efficacy of antiepileptic treatments in suppressing seizures (anti-seizure
      effect), we want to seek for therapies that can lead to plastic, neuromodulatory
      changes in the epileptic network. Neuropharmacological therapy with levetiracetam
      (LEV) and vagus nerve stimulation (VNS) are two novel treatments for refractory
      epilepsy. LEV acts rapidly on seizures in both animal models and humans. In
      addition, preclinical studies suggest that LEV may have antiepileptogenic and
      neuroprotective effects, with the potential to slow or arrest disease
      progression. VNS as well can have an immediate effect on seizures in epilepsy
      models and patients with, in addition, a cumulative effect after prolonged
      treatment. Studies in man are hampered by the heterogeneity of patient
      populations and the difficulty to study therapy-related effects in a systematic
      way. Therefore, investigation was performed utilizing two rodent models mimicking
      epilepsy in humans. Genetic absence epilepsy rats from Strasbourg (GAERS) have
      inborn absence epilepsy and Fast rats have a genetically determined sensitivity
      for electrical amygdala kindling, which is an excellent model of temporal lobe
      epilepsy. Our findings support the hypothesis that treatment with LEV and VNS can
      be considered as neuromodulatory: changes are induced in central nervous system
      function or organization as a result of influencing and initiating
      neurophysiological signals.

PMID- 16898261
TI  - Seasonal variation in concentration and metallic constituents of atmospheric
      particulates near the western coast of central Taiwan.
AB  - In addition to determining the concentration and metallic constituents of
      particulate matter at Taichung Harbor in central Taiwan, this study attempts to
      characterize the mass, metallic elements, composition and concentrations of total
      suspended particulates (TSP), fine particles and coarse particles. Statistical
      approaches, such as the Spearman tests, were also adopted to determine the
      seasonal variations of concentrations of these pollutants. Experimental results
      indicate that the mean TSP, fine particulate and coarse particulate
      concentrations in spring and winter are higher than in summer and autumn on the
      western coast of central Taiwan. Spearman statistical analysis of metallic
      elements Mn and Pb showed high concentration coefficients for fine and coarse
      particulates on the western coast of central Taiwan. The order of mean metallic
      concentrations in TSP, coarse particulates and fine particles was Fe > Zn > Mg >
      Cu> Cr > Mn > Pb in TSP, Fe > Cu > Zn > Mg > Mn > Pb > Cr in coarse particulates
      and Fe > Cu > Mg > Pb > Zn > Mn > Cr in fine particulates.

PMID- 16898262
TI  - Lethal acute lung injury and hypoglycemia after subcutaneous administration of
      monochloroacetic acid.
AB  - Hypoglycemia is suspected in the acute lethal toxicity induced by cutaneous
      exposure to monochloroacetic acid (MCA). Although it has been shown that hepato
      renal dysfunction is involved, the mechanism and the target organs that directly
      affect mortality remain to be determined. We suspected respiratory failure as a
      main cause of death in some reported cases. We investigated dose-response
      effects, hypoglycemia, and lung injury in rats exposed to MCA. Serum glucose,
      blood gases, and parameters of alveolar injury in bronchoalveolar lavage fluid
      (BALF) were analysed 2 and 4 h after subcutaneous administration of MCA (108, 135
      or 163 mg/kg). Apparent pulmonary injury and hypoglycemia were not identified 2 h
      after administration, but lactate dehydrogenase (LDH) and total cells in BALF
      were dose-dependently increased; and severe hypoglycemia was identified 4 h after
      administration. Blood gas analysis showed remarkable alveolar gas dysfunction as
      exchange in the 163 mg/kg group. Thus, hypoglycemia and lung injury appear to
      cause death in response to MCA exposure.

PMID- 16898263
TI  - Melatonin modulates 900 Mhz microwave-induced lipid peroxidation changes in rat
      brain.
AB  - Microwaves (MW) from cellular phones may affect biological systems by increasing
      free radicals, which may enhance lipid peroxidation levels of the brain, thus
      leading to oxidative damage. Melatonin is synthesized in and secreted by the
      pineal gland at night and exhibits anti-oxidant properties. Several studies
      suggest that supplementation with anti-oxidant can influence MW-induced brain
      damage. The present study was designed to determine the effects of MW on the
      brain lipid peroxidation system, and the possible protective effects of melatonin
      on brain degeneration induced by MW. Twenty-eight Sprague-Dawley male rats were
      randomly divided into three groups as follows: (1) sham-operated control group (N
      = 8); (2) study 900-MHz MW-exposed group (N = 8); and (3) 900-MHz MW
      exposed+melatonin (100 microg/kg sc before daily MW exposure treated group) (N =
      10). Cortex brain and hippocampus tissues were removed to study the levels of
      lipid peroxidation as malonyl dialdehyde. The levels of lipid peroxidation in the
      brain cortex and hippocampus increased in the MW group compared with the control
      group, although the levels in the hippocampus were decreased by MW+melatonin
      administration. The brain cortex lipid peroxidation levels were unaffected by
      melatonin treatment. We conclude that melatonin may prevent MW-induced oxidative
      changes in the hippocampus by strengthening the anti-oxidant defense system, by
      reducing oxidative stress products.

PMID- 16898264
TI  - The effect of pregnancy and lactation on bone mineral density in fluoride-exposed
      rats.
AB  - Fluoride increases metabolic turnover of the bone in favour of bone formation.
      Excessive intake of fluoride may lead to pathological changes in teeth and bones:
      dental and skeletal fluorosis. In this study, we investigated the effect of
      pregnancy and lactation on bone mineral density (BMD) in fluoride-exposed rats.
      Female Wistar rats were given commercially available spring water with 100 ppm
      fluoride (N = 8), or without addition (N = 8) for 18 weeks. At 16 weeks of age,
      four female rats and one male rat were kept in a cage for 5 days; all females
      were successfully impregnated. BMD was measured at 16 weeks of age, on the first
      day postpartum, and at the end of lactation. Spinal BMD was significantly higher
      in fluoride-exposed rats than control (P < 0.05), but there were no differences
      in femoral BMD (P = 0.670). During pregnancy, spinal BMD and femoral BMD were not
      significantly changed in fluoride-exposed rats, whereas BMD of the spine was
      significantly decreased in the control rats (P = 0.013), but not in the femur.
      During lactation, BMD was significantly decreased at the two regions compared to
      initial values (P < 0.05) in both groups. This study shows that pregnancy has no
      effect on bone, but lactation has a decreasing effect on BMD in fluoride-exposed
      rats.

PMID- 16898265
TI  - Effects of omega-3 essential fatty acids against formaldehyde-induced nephropathy
      in rats.
AB  - The aim of this study was to examine the toxicity of formaldehyde (FA) on the
      kidney and the protective effects of omega-3 essential fatty acids against these
      toxic effects. Twenty-one male Wistar rats were divided into three groups. Rats
      in Group I comprised the controls, while the rats in Group II were injected every
      other day with FA. Rats in Group III received omega-3 fatty acids daily while
      exposed to FA. At the end of the 14-day experimental period, all rats were killed
      by decapitation and the kidneys removed. Some of the kidney tissue specimens were
      used for determination of superoxide dismutase (SOD), glutathione peroxidase (GSH
      Px) activities, and malondialdehyde (MDA) levels. The remaining kidney tissue
      specimens were used for light microscopic evaluation. The levels of SOD and GSH
      Px were significantly decreased, and MDA levels were significantly increased in
      rats treated with FA compared with those of the controls. Furthermore, in the
      microscopic examination of this group, glomerular and tubular degeneration,
      vascular congestion and tubular dilatation were observed. However, increased SOD
      and GSH-Px enzyme activities, and decreased MDA levels were detected in the rats
      administered omega-3 fatty acids while exposed to FA. Additionally, kidney damage
      caused by FA was decreased and structural appearance was similar to that of the
      control rats in this group. In conclusion, it was determined that FA-induced
      kidney damage was prevented by administration of omega-3 essential fatty acids.

PMID- 16898266
TI  - Demonstration of inter- and intracellular distribution of boron and gadolinium
      using micro-proton-induced X-ray emission (Micro-PIXE).
AB  - Micro-proton-induced X-ray emission (Micro-PIXE) was applied to determine inter-
      and intracellular distribution of boron (10B) and gadolinium (157Gd), the capture
      atoms used to kill tumor cells in neutron capture therapy (NCT). Cultured 9L
      gliosarcoma cells on Mylar film were exposed to sodium borocaptate (BSH) and
      gadobenate dimeglumine (Gd-BOPTA). To analyze the inter- and intracellular
      distribution of 10B and 157Gd in 9L gliosarcoma cells, the cells were irradiated
      using a proton beam of 1.7 or 3 MeV energy collimated to 1 microm diameter and
      emission X-ray was detected. The distribution of 10B and 157Gd in 9L gliosarcoma
      cells was then examined. In this study, we could directly analyze the inter- and
      intracellular distribution of 10B and 157Gd elements in 9L gliosarcoma cells
      directly using Micro-PIXE. This is the first report on the distribution of 10B
      employing a method to detect gamma-rays resulting from the nuclear reaction of
      10B using particle-induced gamma-ray emission (PIGE). These results show that the
      distribution of 157Gd elements was correctly measured using micro-PIXE. 157Gd
      should have the same tendency as 10B in cultured 9L gliosarcoma cells and agree
      with the distribution in 9L gliosarcoma cells. Further investigation is necessary
      for a higher spatial resolution and optimization of the measurement time or
      improvement of the sampling method. In the future, it will be possible to employ
      this method to analyze the intracellular microdistribution of the capture element
      and in the development of new drugs for NCT.

PMID- 16898267
TI  - Quercetin induces p53-independent apoptosis in human prostate cancer cells by
      modulating Bcl-2-related proteins: a possible mediation by IGFBP-3.
AB  - Quercetin, a flavonoid found in onion, grapes, green vegetables, etc., has been
      shown to possess potent antiproliferative effects against various malignant
      cells. We report insulin-like growth factor-binding protein-3 (IGFBP-3) as an
      effector of quercetin-induced apoptosis in human prostate cancer cell lines in a
      p53-independent manner. We evaluated the production of IGFBP-3 in quercetin
      treated cells. Apoptosis was studied in quercetin-treated cells to study the
      IGFBP-3-mediated role with flow cytometry and DNA fragmentation. Protein
      expressions of Bcl-2, Bcl-x(L), and Bax were studied by Western blot. Increased
      production of IGFBP-3 was associated with the increased ratio of proapoptotic to
      antiapoptotic members of the Bcl-2 family. In quercetin-treated PC-3 cells, an
      increase in Bax protein expression and a decrease in Bcl-x(L) protein and Bcl-2
      protein were observed. As PC-3 is a p53-negative cell line, these modulations of
      proapoptotic proteins and induction of apoptosis were independent of p53. The
      level of IGFBP-3 on the response of PC-3 cells to quercetin was examined. There
      was a twofold increase in IGFBP-3 level in conditioned media of 100 microM
      quercetin-treated cells. Quercetin also brought a peak at sub-G1 in PC-3 cells.
      Thus, increased level of IGFBP-3 was associated with increased proapoptotic
      proteins and apoptosis in response to quercetin, suggesting it may be a p53
      independent effector of apoptosis in prostate cancer cells via its modulation of
      the Bax/Bcl-2 protein ratio.

PMID- 16898269
TI  - Schedule-dependent interactions between pemetrexed and cisplatin in human
      carcinoma cell lines in vitro.
AB  - The combination of pemetrexed and cisplatin shows good clinical activity against
      mesothelioma and lung cancer. In order to study the potential cellular basis for
      this, and provide leads as to how to optimize the combination, we studied the
      schedule-dependent cytotoxic effects of pemetrexed and cisplatin against four
      human cancer cell lines in vitro. Tumor cells were incubated with pemetrexed and
      cisplatin for 24 h at various schedules. The combination effects after 5 days
      were analyzed by the isobologram method. Both simultaneous exposure to pemetrexed
      and cisplatin for 24 h and sequential exposure to cisplatin for 24 h followed by
      pemetrexed for 24 h produced antagonistic effects in human lung cancer A549,
      breast cancer MCF7, and ovarian cancer PA1 cells and additive effects in colon
      cancer WiDr cells. Pemetrexed for 24 h followed by cisplatin for 24 h produced
      synergistic effects in MCF7 cells, additive/synergistic effects in A549 and PA1
      cells, and additive effects in WiDr cells. Cell cycle analysis of MCF7 and PA1
      cells supported these findings. Our results suggest that the simultaneous
      clinical administration of pemetrexed and cisplatin may be suboptimal. The
      optimal schedule of pemetrexed in combination with cisplatin at the cellular
      level is the sequential administration of pemetrexed followed by cisplatin and
      this schedule is worthy of clinical investigations.

PMID- 16898270
TI  - Synthesis and antimelanoma activity of reversed amide analogues of N-acetyl-4-S
      cysteaminylphenol.
AB  - The melanin biosynthetic pathway from tyrosine is a potential target for
      combating malignant melanoma. N-Acetyl-4-S-cysteaminylphenol 1 is a previously
      synthesized analogue of tyrosine that probably acts by this pathway. It
      interferes with cell growth and proliferation via selective oxidation in
      melanocytes to an oquinone that can alkylate cellular nucleophiles. We previously
      synthesized a range of analogues of the original lead compound 1 most of which
      displayed greater cytotoxicity than 1. Eighteen new analogues with the amide
      group reversed have now been synthesized and tested for antimelanoma activity.
      Most of these reverse amides showed greater cytotoxicity than N-acetyl-4-S
      cysteaminylphenol towards five representative melanoma cell lines. The highest
      cytotoxicity was observed for the piperidine and hexamethyleneimine derivatives
      7, 8, 12, 13, and 17 and the catechol 18. The most active compound, 7, had
      cytotoxicity comparable to cisplatin against the five melanoma cell lines. The
      moderate activity of 7 and 18 against SK-Mel-24 (non-tyrosinase containing) and
      an ovarian cell line suggests that interference with the melanin pathway may not
      be the only mode of action of these compounds. Assays of some of the compounds as
      substrates for tyrosinase showed that the catechol 18 was the best substrate and
      that the piperidine derivative 7 was the best substrate of the phenolic compounds
      synthesized.

PMID- 16898268
TI  - Different forms of prolactin have opposing effects on the expression of cell
      cycle regulatory proteins in differentiated mammary epithelial cells.
AB  - Prolactin (PRL) is a hormone that contributes to both the growth and
      differentiation of mammary epithelial cells, activities likely to impact breast
      cancer in opposite ways. Whether PRL causes growth or differentiation has been
      solely attributed to the coexisting steroidal environment, with PRL stimulating
      mammary gland growth during pregnancy, and then milk production after the
      postpartum drop in estrogen and progesterone. However, previous work from our
      laboratory has shown that the form of PRL may also be an important factor. During
      pregnancy, unmodified PRL (U-PRL) promotes mammary growth, while an increase in
      phosphorylated PRL, or administration of a molecular mimic of phosphorylated PRL
      (S179D PRL), inhibits growth. Unknown, however, is whether these forms of PRL
      have opposite effects on growth in the absence of steroids and whether effects
      are directly on mammary epithelial cells. To mimic the glandular epithelium in
      vitro, we used contact-inhibited, differentiated cells and showed that even with
      these minimally growing cells that treatment with U-PRL caused increased
      expression of cyclin D1 and cyclin-dependent kinase 4, increased activity of both
      cdk4 and cdk2, while having no effect on the inhibitory protein, p21. S179D PRL,
      by contrast, had no effect on cyclin D1 and cdk4 expression, but increased p21
      expression and expression of the vitamin D receptor (VDR). We conclude that
      increased U-PRL or decreased phosphorylated PRL can directly affect cell cycle
      control proteins in relatively differentiated mammary epithelial cells, thereby
      implicating the balance between these two forms of PRL in the early promotion of
      breast cancer.

PMID- 16898271
TI  - Physical activity and acculturation among adult Hispanics in the United States.
AB  - Understanding the prevalence and demographic correlates of physical activity is
      important for public health and epidemiological research. This analysis examines
      the association between acculturation and physical activity in a large
      (approximately 5,000) sample of Hispanic adults from the 2000 National Health
      Interview Survey. Scores for eight questions concerning language use were summed
      to produce an acculturation index. Factor analysis indicated that these questions
      assessed a single underlying construct. Self-reported adherence to
      recommendations concerning leisure time physical activity increased from 22. 6%
      in the least acculturated tertile to 47% in the most acculturated tertile. In
      contrast, prevalence of walking or bicycling for errands decreased from 25.2 to
      18.2%, and prevalence of standing or walking during most of the day decreased
      from 82.8 to 65.6% as acculturation increased. Thus, patterns of physical
      activity associated with leisure versus nonleisure time differed among Hispanics
      with varying acculturation levels. Alternatively, cultural factors may have
      differential effects on responses to questions concerning leisure and nonleisure
      time physical activity. In either case, assessing both types of activity is
      important for monitoring and understanding Hispanic health behaviors and
      interpreting epidemiological studies that involve physical activity in Hispanics.

PMID- 16898272
TI  - Puberty and physical self-perceptions of competitive female figure skaters: an
      interdisciplinary approach.
AB  - This study considered the interrelationships among biological maturation and its
      physical correlates, social physique anxiety, and appearance-related physical
      self-perceptions in 113 adolescent female figure skaters participating in solo (n
      = 73) or partner contexts (n = 40). Participants were interviewed about their
      menarcheal status, underwent a battery of anthropometric measurements, and
      completed the Physical Self Description Questionnaire and the Social Physique
      Anxiety Scale. Menarcheal status was a stronger correlate of physical self
      perceptions than age. A combination of biological and psychological
      characteristics accounted for 25% of the variance in appearance-related physical
      self-perceptions. Younger, premenarcheal, ectomorphic skaters reporting lower
      social physique anxiety were more satisfied with their body fat and sport
      competence but reported lower self-esteem, global physical self-concept, and
      appearance scores. Skating context did not predict physical self-perceptions.

PMID- 16898273
TI  - Assessing preschool children's physical activity: the Observational System for
      Recording Physical Activity in children-preschool version.
AB  - In this paper we present initial information concerning a new direct observation
      system-the Observational System for Recording Physical Activity in Children
      Preschool Version. The system will allow researchers to record young children's
      physical activity levels while also coding the topography of their physical
      activity, as well as detailed indoor and outdoor social and nonsocial contextual
      information. With respect to interobserver agreement (IOA), the kappa and
      category-by-category agreement mean of those obtained for the three illustrative
      preschools were generally above .80. Hence, our IOA data indicated that trained
      observers in the three preschools frequently agreed on the eight observational
      categories and accompanying codes. The results for preschoolers' level of
      physical activity indicated they spent the majority of observational intervals in
      sedentary activity (i.e., more than 80% intervals) and were observed in moderate
      to vigorous physical activity much less frequently (i.e., 5% or fewer intervals).
      For the 15 indoor and 12 outdoor activity contexts, variability across both the
      activity contexts and the three preschools were evident. Nevertheless, three
      classroom contexts-transition, snacks, and naptime--accounted for the greatest
      porportion of coded activity contexts for the children. In the three preschools,
      4 of 17 physical activity types--sit and squat, lie down, stand, and walk-
      accounted for the topography of much of children's physical activity behavior
      Systematic observation of more representative preschool samples might better
      inform our present understanding of young children's physical activity in
      community preschool programs.

PMID- 16898274
TI  - Error detection processes during observational learning.
AB  - The purpose of this experiment was to determine whether a faded knowledge of
      results (KR) frequency during observation of a model's performance enhanced error
      detection capabilities. During the observation phase, participants observed a
      model performing a timing task and received KR about the model's performance on
      each trial or on one of two trials. Delayed retention and transfer tests were
      used to assess the observer's ability to detect error in the model's performance
      and in the participant's performance while physically practicing the task.
      Results indicated a beneficial effect of a reduced KR frequency for performance
      stability and the ability to detect errors in both the model and the
      participant's own performance. The results suggest that aspects of the processing
      mechanism(s) developed in observational learning and related to KR are probably
      similar to those developed through physical practice.

PMID- 16898275
TI  - Teachers' and students' conceptions of ability in elementary physical education.
AB  - Using Nicholl's (1989) and Dweck 's (1999, 2002) theories on ability as
      conceptual frameworks, this study explored teachers' and students' conceptions of
      ability in elementary physical education. Participants were 8 physical education
      specialists from five public schools and 160 students from their second- and
      fourth-grade classes. Teacher and student interviews and questionnaires were used
      for data collection. When asked to describe the "best" and "poorest" students in
      their physical education classes, teachers defined or referenced student status
      solely in terms of class behavior and effort, such as participation and working
      hard. In contrast, students primarily used ability-related indicators, such as
      task mastery and social comparison along with class behavior as criteria of their
      own ability. Overall, teachers and students had different views of "good"
      students in elementary physical education. In an era of standards-based learning
      and accountability in education, teachers may need to focus more on a task
      involved climate by taking into account student learning and achievement.

PMID- 16898276
TI  - Fourth-grade students' motivational changes in an elementary physical education
      running program.
AB  - Achievement goal theory and the expectancy-value model of achievement choice were
      used to examine fourth-grade students' motivational changes in an elementary
      physical education running program. In fall and spring of the school year,
      participants (N = 113; 66 boys, 47 girls) completed questionnaires assessing
      achievement goals, expectancy beliefs, subjective task values, and intention for
      future running participation. They also completed a timed 1-mile (1.6 km) run.
      The number of laps they ran/walked during the school year was used to assess
      students' persistence/effort. Results indicated the students improved their run
      but became less motivated about running while participating in a year-long
      running program. Children's beliefs about how good they were in the running
      program (i.e., expectancy beliefs) and their perceptions of how interesting and
      fun it was (i.e., interest) emerged as the strongest positive predictors of their
      motivation for running over time. These findings provide strong empirical
      evidence that expectancy beliefs and interest are essential to children's
      motivation in elementary physical education.

PMID- 16898277
TI  - Analysis of exchanges between novice and cooperating teachers during internships
      using the NCATE/NASPE Standards for Teacher Preparation in Physical Education as
      guidelines.
AB  - To be recognized as an accredited program, Physical Education Teacher Education
      (PETE) programs in the country must abide by guidelines put forward by the
      National Association for Sport and Physical Education (NASPE), in collaboration
      with the National Council for the Accreditation of Teacher Education (NCATE). The
      guidelines are divided into nine standards and identify a number of outcomes
      (NASPE, 1998). The purpose of this study was to determine the nature of the
      exchanges between novice teachers (NTs) and cooperating teachers (CTs), when
      using the NASPE Standards (1998) as a reference point, and determine if the focus
      of the exchanges differed over time and according to data source. Six pairs of
      CTs and their NT participated in the study. Data were collected through recorded
      conversations between NTs and their CT as well as NTs' logs. Data showed that the
      majority of conversations focused on planning and instruction (Standard 6) and
      management and motivation (Standard 4), while few related to diverse learners
      (Standard 3), growth and development (Standard 2), and communication (Standard
      5). The small amount of information shared by CTs in some standards indicates a
      need for PETE programs to share the guidelines with CTs to make them aware of the
      importance of offering a variety of topics to interns, because CTs are the
      primary source of information during this crucial experience.

PMID- 16898278
TI  - "...lf I had a choice, I would..." a feminist poststructuralist perspective on
      girls in physical education.
AB  - A significant number of studies evidence girls' lack of participation in physical
      education. This study used feminist poststructuralism to examine the ways in
      which high school girls participated in or resisted physical education. Using
      qualitative research methods, researchers collected field notes, informal
      interviews, and formal interviews with the teacher and 15 female students. In
      contrast to previous studies, girls in this study enjoyed and valued physical
      activity. As active agents, they chose to participate in or resist specific
      physical activities through their negotiations of gender relations. Physical
      education classes emerged as a contested terrain in which girls supported the
      notion of equal opportunity in physical activity but perceived limits on their
      choices in physical education as compared to male peers.

PMID- 16898279
TI  - Relationship between exercise heart rate and music tempo preference.
AB  - The present study examined the predicted positive and linear relationship
      (Iwanaga, 1995a, 1995b) between exercise heart rate and music tempo preference.
      Initially, 128 undergraduate students (M age = 20.0 years, SD = 0.9) were
      surveyed to establish their three favorite music artists. A separate experimental
      group of 29 undergraduates (M age = 20.3 years, SD = 1.2) selected the music of a
      single artist from the three highest-rated artists from the earlier survey. They
      reported their preference for slow, medium, and fast tempo selections from each
      artist for three treadmill walking conditions at 40%, 60%, and 75% maximal heart
      rate reserve. A mixed-model 3 x 3 x 2 (Exercise Intensity x Music Tempo x Gender)
      analysis of variance was used to analyze the data. Results indicated there was no
      three-way interaction for music preference. There was, however, a significant (p
      < .05) two-way interaction for Exercise Intensity x Music Tempo (partial eta2 =
      .09) and a significant (p < .05) main effect for music tempo, with large
      differences evident between preference for medium versus slow tempo and fast
      versus slow tempo music at all exercise intensities (partial eta2 = .78).
      Participants reported a preference for both medium and fast tempo music at low
      and moderate exercise intensities and for fast tempo music at high intensity.
      Only partial support was found for the expected linear relationship between
      exercise intensity and music tempo preference.

PMID- 16898280
TI  - Training physical education students to self-regulate during basketball free
      throw practice.
AB  - The additive effects of self-regulation training in forethought, performance, and
      self-reflection phase processes on acquiring a novel motoric skill (i.e.,
      basketball free throws) and self-reflective beliefs were studied with 50 college
      students. The results showed a positive linear trend between the number of self
      regulatory phases, in which the participants were trained, and their free throw
      shooting performance and shooting adaptation. The two- and three-phase training
      groups displayed significantly more accurate free throws and were able to self
      correct their shooting form more frequently following missed shots than all other
      groups. Participants who received three-phase training displayed the most
      adaptive motivational profile, characterized by making strategic attributions and
      adaptive inferences and by using self/process criteria during self-evaluations.

PMID- 16898281
TI  - Self-confidence as a mediator of the relationship between competitive anxiety
      intensity and interpretation.
AB  - The aim of this study was to examine whether self-confidence mediated the
      relationship between competitive anxiety intensity and direction. Elite (n = 102)
      and nonelite (n = 144) participants completed the self-confidence subscale of the
      Competitive Trait Anxiety Inventory-2 and the worry and somatic subscales from
      the Sport Anxiety Scale. Consistent with procedures recommended by Baron and
      Kenny (1986), linear regression analyses were used. The findings for elite
      athletes revealed worry intensity to significantly predict self-confidence and
      worry direction. However, when self-confidence was controlled, worry intensity
      did not predict worry direction over that which was significantly predicted by
      self-confidence. Within the analysis for somatic symptoms, only self-confidence
      was found to predict somatic symptom direction. For the nonelite athletes, worry
      and somatic symptom intensity predicted both self-confidence and direction, and
      direction when self-confidence was controlled. The findings for the elite
      athletes suggest self-confidence mediates the relationship between performers'
      worry symptoms and subsequent directional interpretations. However, the findings
      suggest that high levels of self-confidence and low symptom intensity are needed
      for nonelite athletes to demonstrate a less debilitative interpretation.

PMID- 16898282
TI  - Performance breakdown in sport: the roles of reinvestment and verbal knowledge.

PMID- 16898284
TI  - [Concerning the work of dissertation councils conferring academic degrees].

PMID- 16898283
TI  - Faculty and male football and basketball players on university campuses: an
      empirical investigation of the "intellectual" as mentor to the student athlete.

PMID- 16898285
TI  - [The perspectives of improvement of the postgraduation education of specialists
      working in military forensic-and-medical organizations].
AB  - The problem of work organization improvement of military forensic examination
      concerning the system of preparing specialists for forensic-and-medical
      organizations of the Russian Ministry of Defense is investigated in the article.
      The directions of development of the postgraduation education system for
      specialists in military forensic examination organizations as well as the main
      targets of the forensic medicine faculty in this sphere are reflected.

PMID- 16898286
TI  - [The prostate gland congestion in young servicemen].

PMID- 16898287
TI  - [New effective methods of onychomycosis therapy in servicemen].

PMID- 16898288
TI  - [Community-acquired pneumonia in the elderly: the peculiarities of the clinical
      picture, diagnosis and treatment].
AB  - The article presents the results of studying the peculiarities of the clinical
      picture, diagnosis and treatment for community-acquired pneumonia in the elderly
      in view of the interaction of combined pathology of respiratory, cardiovascular
      and urological systems in order to optimize medical-and-diagnostic support of the
      above-mentioned category of patients in conditions of the pulmonology department
      of versatile educational establishment. Optimization of all-round inspection of
      the sick with pneumonia in the advanced age at an initial stage of treatment in
      conditions of the pulmonology department so as to reveal the aggravation of
      internal bodies' combined diseases will allow making early correction of
      aetiotropic, pathogenetic and symptomatic combined pathology therapy available,
      which reduces the terms of staying at hospital without damage of diagnosis and
      treatment.

PMID- 16898289
TI  - [The morphologic and functional state of the kidneys exposed to focused waves
      during remote nephro-lithotripsy].
AB  - Clinical and experimental research has shown that complications connected with
      negative influence of focused waves in distant lithotripsy in litotripters with
      an electrohydravlic system of focused waves generation depend on many factors,
      including the regime of wave generator work, an electrode interval, defocusing
      the wave as a result of an electrode interval center displacement, the amplitude
      of pressure and the length of a wave impulse in positive and negative phases. The
      wave impulse is distorted, which leads to kidney tissue damage.

PMID- 16898290
TI  - [Metastatic tumors of brain].

PMID- 16898291
TI  - [The change of morphometrical structure of the optic nerve disk depending on the
      amplitude of intraocular pressure daily fluctuations].

PMID- 16898292
TI  - [The opportunities of the treatment for patients with disseminated prostate gland
      cancer (the survey of literature)].

PMID- 16898293
TI  - [The modern methods of radiation visualization in diagnostics of blood system
      diseases].

PMID- 16898294
TI  - [Some theoretical and methodological problems of modern rhinology (the survey of
      literature)].

PMID- 16898295
TI  - [Scientific and practical aspects of modern technologies for obtaining purified
      water and water for injection in field conditions].
AB  - Nowadays drug stores of military-and-field medical organizations use the method
      of distillation for obtaining cleaned water and water for injection and use
      distillators as a technical means, which does not ensure that the water obtained
      has stated indices of quality. It was found out that it is the most efficient to
      use the technology basing on the complex usage of filtering, osmotic, ionic
      processes for obtaining cleaned water and water for injection from surface
      natural springs, which ensures minimal usage of resources and energy and the
      unity of constructional and technological peculiarities of cleaning water
      methods.

PMID- 16898296
TI  - [Subacute thyroiditis in practice of a clinician].

PMID- 16898297
TI  - [Concerning servicemen's right for medical-and-social expertise].

PMID- 16898298
TI  - [An outstanding scientist and military-and-field surgeon (to the 100th
      anniversary of the birthday of Vishnevskii A.A.)].

PMID- 16898299
TI  - [Questions of the Russian army's medical support in legal acts of the 18th
      century].

PMID- 16898300
TI  - [The district military-and-clinical hospital of the Northern Caucasus military
      district is 65 years].

PMID- 16898301
TI  - Pain management: trends and challenges.

PMID- 16898302
TI  - Initial experience of laparoscopic incisional hernia repair.
AB  - Laparoscopic repair of ventral and incisional hernia has become increasingly
      popular as compared to open repair. The procedure has the advantages of minimal
      access surgery, reduction of post operative pain and the recurrence rate. A
      prospective study of laparoscopic incisional hernia repair was performed in our
      center from August 2002 to April 2004. Eighteen cases (n: 18) were performed
      during the study period. Fifteen cases (n: 15) had open hernia repair previously.
      Sixteen patients (n: 16) had successful repair of the hernia with the
      laparoscopic approach and two cases were converted to open repair. The mean
      hernia defect size was 156cm2. There was no intraoperative or immediate
      postoperative complication. The mean operating time was 100 +/- 34 minutes (75 -
      180 minutes). The postoperative pain was graded as mild to moderate according to
      visual analogue score. The mean day of discharge after surgery was two days (1 -
      3 days). During follow up, three patients (16.7%) developed seroma at the hernia
      sac which was resolved with conservative management after three weeks. One (5.6%)
      patient developed recurrence six months after surgery. In conclusion,
      laparoscopic repair of incisional hernia particularly recurrent hernia has been
      shown to be safe and effective in our centre. However, careful patient selection
      and acquiring the necessary advanced laparoscopic surgical skills coupled with
      the proper use of equipment are mandatory before embarking on this procedure.

PMID- 16898303
TI  - Tracheobronchial stenting is safe and effective in relieving upper airway
      obstruction.
AB  - Many studies have shown that tracheobronchial stenting is effective in relieving
      respiratory distress secondary to major airway obstruction due to lung or
      oesophageal cancer. A retrospective review on the benefits and complications of
      self-expandable metallic stent (SEMS) insertion through flexible bronchoscopy for
      the palliative treatment of upper airway obstruction in University Malaya Medical
      Centre was performed. Ten patients underwent this procedure. Relief of dyspnoea
      was immediate following stent insertion in all patients. Stent migration occurred
      in one patient and three patients had restenosis of the central airway. We
      conclude that tracheobronchial stenting via flexible bronchoscopy is feasible and
      safe.

PMID- 16898304
TI  - Neck abscess: five year retrospective review of Hospital University Kebangsaan
      Malaysia experience.
AB  - The most commonly involved space was the parapharyngeal and superficial anterior
      triangle followed by submandibular, retropharyngeal, posterior triangle and
      submental spaces respectively. Thirty-three percent of patients had diabetes
      mellitus as a predisposing factor. More than half of them had no known
      aetiological cause for the neck abscess. We encountered one mortality in an
      elderly patient with diabetes who succumbed to overwhelming septicaemia despite
      early abscess drainage and intensive medical treatment.

PMID- 16898305
TI  - Comparison of the ease of insertion of the laryngeal tube VBM and laryngeal mask
      airway during manual in-line neck stabilization.
AB  - The purpose of this study is to assess whether the newly developed laryngeal tube
      (LT) VBM is easy, simple to use and able to provide adequate ventilation and
      oxygenation to a patient with an unstable neck who required airway management. We
      compared the LT to the laryngeal mask airway (LMA) as alternative airway
      management tool in adult patient with unstable neck who underwent intubation with
      manual in-line neck stabilization. A randomized single-blinded prospective study
      was conducted involving a total of 40 ASA I and II premedicated patients who were
      divided into two groups with 20 patients for each group; either LT or LMA group
      for airway management during elective surgery. After preoxygenation, anaesthesia
      was induced and neuromuscular blockade was produced with intravenous drugs. The
      LT or LMA was inserted after neuromuscular blockade was confirmed using a
      peripheral nerve stimulator (TOF 1). A size 3, 4 or 5 LT OR a size 3 or 4 LMA was
      inserted while the patient's head and neck were being stabilized by an assistant
      who held the sides of the neck and the mastoid processes (manual in-line
      stabilization). If it was not possible to ventilate the lungs, or if endotrachial
      carbon dioxide (ETCO2) and/or chest movement did not indicate a patent airway,
      the LT or LMA was removed. After three failed attempts, the study was terminated
      and the airway was secured in the most suitable manner determined by the
      anaesthetist. There was a statistically significant difference for both groups in
      the time required for successful insertion (time required for LT was 24.8 +/- 7.7
      seconds and LMA was 36.1+/-17.3 seconds) (p= 0.01). There was no statistical
      differences (p>0.05) in number of attempts needed to achieve a patent airway
      although we were able to achieve a clear airway in all patients in LT group at
      the first attempt compared with 85% in LMA group. successful insertion rate was
      100% for both groups. We conclude that the LT is easier to insert and is a
      suitable alternative to the LMA for airway management when the patient's head and
      neck are stabilized by manual in-line method.

PMID- 16898306
TI  - Pain morbidity in primary care - preliminary observations from two different
      primary care settings.
AB  - The prevalence of pain complaints as a reason for patient-doctor encounters in
      the local primary care setting is unknown. We performed a cross-sectional survey
      of such encounters in one public primary care clinic (KK) and 17 general practice
      clinics (GP), from the city of Seremban, Negeri Sembilan, Malaysia. Reasons for
      visits were recorded by doctors in KK and medical students in GP using a
      structured questionnaire. Morbidity data was coded using the International
      Classification of Primary Care (ICPC-2). A total of 2234 encounters were recorded
      (80.9% from KK, 19.1% from GP). The overall prevalence of pain complaints was
      31.9% with a significant difference between the two cohorts (KK 28.7% and GP
      45.2%, p<0.001). Musculoskeletal pain complaints were more common in KK than GP
      (40.9% versus 29.7%, p<0.05). Of the 3 main ethnic groups in Malaysia (Malay,
      Chinese and Indian) the Indian patients at KK had the highest prevalence of pain
      complaints and the Chinese at the GP had the lowest. Thus pain was a common
      complaint in the two different primary care settings studied. Some of the
      differences observed are probably due to the differences in the healthcare
      seeking behaviour of patients consulting at these two settings as well as
      differences in the payment systems.

PMID- 16898307
TI  - Outbreak of influenza amongst residential school students in Malaysia.
AB  - In the months of July and August 2003, an outbreak of acute respiratory illness
      caused by influenza A virus occurred among students in seven residential schools
      situated in the northern part (Perak) of Peninsular Malaysia. Out of 4989
      students, aged 13 to 18 years (mean = 15.9), 1419 (28%) were effected by
      influenza-like illness. All patients were treated as outpatients except for 36
      students who required admission for high fever, severe coughing and shortness of
      breath. Abnormal chest X-ray findings were noted for those that required
      inpatient management. Influenza A virus was isolated from 37 sputum specimens, 20
      throat swabs and three nasal swab specimens from a total of 278 clinical samples
      obtained from 180 patients. Isolates from each of the outbreaks were sent to WHO
      Collaborating Centre for Reference and Research on Influenza, Melbourne,
      Australia for antigenic and genetic analysis. One school outbreak was due to
      influenza A (H1N1), A/New Caledonia/20/99-like virus while the other six school
      outbreaks were due to influenza A (H3N2) viruses which were A/Fujian/411/2002
      like).

PMID- 16898308
TI  - A preliminary finding: immunohistochemical localisation and distribution of
      placental angiotensin II receptor subtypes in normal and preeclamptic
      pregnancies.
AB  - Pre-eclampsia or pregnancy induced hypertension (PIH) affects 6-8% of all
      pregnancies. Although the underlying mechanism of PIH is still unknown, it is
      widely believed that the placenta plays an important role. It was thought that an
      ischemic placenta due to poor perfusion can precipitate the signs and symptoms of
      PIH. This study aims to investigate the possible role of Type 1(AT1) and Type 2
      (AT2) angiotensin II receptor subtypes in the mechanism of PIH. AT1 receptor
      stimulation causes vasoconstriction and AT2 receptor stimulation causes
      vasodilatation. Investigating the interactions of these two receptors in the
      placenta provides an insight as to the balance that may exist between AT1 and AT2
      receptors in normal pregnancy. Any disruption to the balance might cause a
      disruption of the blood flow in the placenta, leading to PIH. Placentas were
      collected from 11 PIH patients and 11 normal patients. Immunohistochemistry
      techniques were performed on the placental tissue to determine the distribution
      of AT1 and AT2 receptors in the placental tissue qualitatively and
      quantitatively. It was observed that in normal patients, the balance between AT1
      and AT2 receptors is that the level of AT2 receptors is higher than the level of
      AT1 receptors. However in the PIH patient, it was observed that the normal
      balance was disrupted. In PIH patients the level of AT1 receptors was observed to
      be higher than the level of AT2 receptors. This study suggests that disruption of
      the balance between AT1 and AT2 receptors observed in PIH placentas might cause a
      decrease in blood flow to the placenta, causing it to be poorly perfused. This
      may cause placental ischemia which may lead to PIH.

PMID- 16898309
TI  - Prophylactic antibiotics in orthopaedic surgery: guidelines and practice.
AB  - The national clinical practice guideline has recommended that prophylactic
      antibiotic be given in orthopaedic surgery involving joint replacements and
      internal fixation of fractures. The aim of this study is to assess the current
      antibiotics prophylaxis practice in a state level hospital. One hundred and three
      patients (68 males, 35 females; mean age 41.6 +/- 22.2 years) undergoing internal
      fixation for closed fractures and joint replacement surgery were included in this
      prospective study. The choice of pre and post-operative antibiotics, their
      dosages and duration of administration were recorded. The pre-operative
      antibiotics were only deemed to have been given if it was documented in the case
      notes and in the case of post-operative antibiotics if it was signed on the drug
      chart. Eighty eight percent were given pre-operative prophylactic antibiotics and
      92% were given post-operative antibiotics. For patients undergoing internal
      fixation of fractures, the most commonly used antibiotic for both pre and post-op
      is intravenous cefuroxime. For joint replacement surgery, the most commonly used
      antibiotic is intravenous cefoperazone. The duration or number of doses of post
      operative antibiotics was highly variable. It was not stated in 56% of the post
      operative instructions. Post-operative antibiotic was ordered for 48 hours or
      longer in 10%. In conclusion, prophylactic antibiotics appear to be widely
      practised. The first line antibiotics as recommended by the present guideline
      were not given in any of the patients. Second generation followed by third
      generation cephalosporins are the most popular antibiotics, with a trend towards
      using third generation cephalosporins in arthroplasty patients. Single dose
      prophylaxis was rarely practised.

PMID- 16898310
TI  - Blood pressure variability and arterial elasticity in hypertensive subjects.
AB  - Apart from the mean 24 hour ambulatory blood pressure (ABP), the blood pressure
      variability (BPV) also bears an independent relationship with target-organ damage
      in hypertension. A reduction in arterial compliance has been demonstrated in
      hypertension but its relation to BPV is still unknown. The aim of the study is to
      compare BPV and arterial compliance between hypertensive and normotensive
      subjects. Eighteen hypertensives and 18 controls were enrolled. Noninvasive 24
      hour ABP monitoring was performed with BR-102 monitor (Schiller Inc. Germany).
      Arterial compliance was determined by the HDI/Pulsewave Research Cardiovascular
      Profiling Instrument (Hypertension Diagnostic Inc. USA). There were significantly
      higher systolic, diastolic and mean arterial BPV in hypertensives as compared to
      normotensive group. Only systolic BPV remained significantly high in
      hypertensives during night time. There were lower arterial compliances in
      hypertensive as compared to normotensive group. No significant relationship
      however was found between BPV and arterial compliance in hypertensive subjects.
      In conclusion, there were higher BPV and lower arterial compliances in
      hypertensive subjects as compared to normotensive subjects.

PMID- 16898311
TI  - Pneumatic reduction of intussusception using equipment readily available in the
      hospital.
AB  - The purpose of this study was to determine the effectiveness of pneumatic
      reduction of intussusception using equipment readily available in the hospital.
      Twenty-two children aged between four months and four years had pneumatic
      reduction of intussusception. The device used was assembled using (i) a hand-held
      pump attached to a pressure gauge, and (ii) a 3-way Foley's balloon catheter.
      There was a 73% success rate and there were no complications. The device used was
      effective and safe for the pneumatic reduction of intussusception.

PMID- 16898312
TI  - Quality assurance in mammography: College of Radiology Survey in Malaysia.
AB  - Malaysia's mammography QA practice was surveyed based on the Malaysian Ministry
      of Health and the American College of Radiology (ACR) requirements. Data on
      mammography unit, processor, image receptor, exposure factors, mean glandular
      dose (MGD), sensitometry, image quality and viewbox luminance were obtained. Mean
      developer temperature and cycle time were 34.1 +/- 1.8degreesC and 107.7 +/- 33.2
      seconds. Mean base+fog level, speed index and contrast index were 0.20+/-0.01,
      1.20+/-0.01 and 1.33+/-0.26 respectively. Eighty-six percent of the fifty centres
      passed the image quality test while 12.5% complied with ACR recommended viewbox
      luminance. Average MGD was 1.0+/-0.4 mGy. Malaysia is on the right track for QA
      but with room for total quality improvement.

PMID- 16898313
TI  - Paediatric tracheostomy in Hospital University Kebangsaan Malaysia - a changing
      trend.
AB  - Indication for pediatric tracheostomy has changed. Upper airway obstruction
      secondary to infectious disorders is no longer the commonest indication. The aim
      of this study was to establish data on indications, outcome and complications of
      pediatric tracheostomy. A retrospective analysis of pediatric tracheostomies
      carried out between March 2002 to March 2004 was done. Eighteen patients were
      identified. The commonest indication was prolonged ventilation (94.5%) followed
      by pulmonary toilet (5.5%). None was performed for upper airway obstruction.
      Postoperative complications were encountered in six patients (33.3%), the
      commonest being accidental decannulation notably in children less than six years
      of age. Twelve patients (66.6%) were successfully decannulated. The mortality
      rate was 16.6%. All death were non tracheostomy related. The commonest indication
      for tracheostomy was prolonged ventilation and tracheostomy in children is
      relatively safe despite complications.

PMID- 16898314
TI  - Implementing an assessment-based communication skills training in pre-clinical
      phase: an IMU experience.
AB  - This article describes the communication skills programme of the International
      Medical University, which adopts an integrated medical curriculum. The programme,
      implemented in February 2005, is based on a systematic framework aimed at
      teaching students basic interpersonal communication skills progressively and
      continuously throughout the pre-clinical phase.

PMID- 16898315
TI  - Screening of concurrent alpha-thalassaemia 1 in beta-thalassaemia carriers.
AB  - Thalassaemia is an inherited blood disorder and is a significant public health
      problem in Malaysia, with many not knowing they carry the gene for thalassaemia.
      The two major forms are alpha and beta thalassaemia. An individual can co-inherit
      both the alpha and beta thalassaemia genes. This study determined the frequency
      of concurrent carriers of alpha thalassaemia in 231 beta thalassaemia carriers.
      Gap-PCR was done on extracted DNA of the beta thalassaemia samples to check for
      alpha thalassaemia 1 molecular defect. Eight (3.5%) samples were found to have
      concurrently inherited the alpha thalassaemia 1 (- -SEA) deletion. The
      significant carrier rate for alpha thalassaemia 1 indicates the need for the
      implementation of DNA analysis to complement thalassaemia screening in high risk
      populations.

PMID- 16898316
TI  - Re-emergence of Chikungunya virus in Malaysia.
AB  - An outbreak of Chikugunya (CHIK) fever occurred among the fishing community in
      Bagan Pancor, Perak. The outbreak was laboratory confirmed within 48 hours after
      the receipt of the specimens. Fifty-three patients' serum samples were submitted
      for laboratory investigation and 47 (88.7%) were confirmed to be positive for
      CHIK infection by RT-PCR, and/or virus isolation, and/or in-house
      immunoflourescent test. RT-PCR and virus isolation were the tests of choice for
      patients with illness of four days or less and detection of CHIK specific IgM for
      those with more than four days of fever. The nucleic acid sequence based on the
      354- and 294-bp of the nsP1 and E1 genes of the CHIK virus detected from pools of
      adults Aedes aegypti mosquitoes were identical to those CHIKV virus isolated from
      humans in the same locality. Phylogenetic analysis of the CHIK virus based on the
      257 nts partial E1 gene indicates that Bagan Panchor's strain was closely related
      to the first CHIK virus isolated during the outbreak in Klang in 1998.

PMID- 16898317
TI  - Bilateral maxillary sinus cholesterol granuloma: a rare entity.
AB  - Cholesterol granuloma in the paranasal sinuses is rare. It is more common in the
      mastoid antrum and temporal bone air cells in chronic middle ear disease. A case
      of bilateral maxillary sinus cholesterol granuloma that mimics chronic maxillary
      sinusitis is reported. This is the first reported case of cholesterol granuloma
      of the maxillary sinus in the Malaysian Literature.

PMID- 16898318
TI  - Third ventricular cavernous angioma.
AB  - Third ventricular cavernous angiomas are rare vascular malformations of the
      brain. We report an eight-year old boy with a rare third ventricular cavernous
      angioma that hemorrhaged presenting with symptoms of acute hydrocephalus.
      Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) showed a
      heterogenous ill-defined, solid and cystic intraventricular mass in the third
      ventricle which was mildly enhanced with contrast and there was associated
      hydrocephalus. The mass was removed with success and follow up after two years
      revealed no neurological abnormalities.

PMID- 16898319
TI  - Ingestion of a voice-master prosthesis followed by a potentially fatal
      aspiration.
AB  - Various complications are associated with the use of indwelling voice prostheses.
      We present problems faced by a patient with his Voice-Master prosthesis, the
      ingestion of the prosthesis followed by a potentially fatal aspiration. The Voice
      Master is unique in that in can be re-inserted. The safety strap is removed after
      primary insertion once the prosthesis is secure. However, during re-insertions
      this safety mechanism is no longer present. Therefore we recommend the placement
      of a temporary stitch or tie to minimize the risks of ingestion or aspiration of
      the prosthesis during re-insertions.

PMID- 16898320
TI  - Malignant myeloid transformation in a child with severe congenital neutropenia
      (Kostmann's syndrome).
AB  - We report a case of a child with severe congenital neutropenia (Kostmann's
      syndrome) who was treated with daily prophylactic subcutaneous granulocyte colony
      stimulating factor (G-CSF) from the age of eight to sixteen years before being
      discontinued for poor haematological and clinical response. She did not have a
      HLA-matched sibling to enable bone marrow transplantation. She subsequently
      developed acute megakaryoblastic leukemia at the age of 17 years and succumbed
      during induction chemotherapy. The role of G-CSF in the pathogenesis of her
      malignant transformation to AML is complicated as this disorder has a propensity
      for myelodysplasia or AML as part of its natural history.

PMID- 16898321
TI  - COBB syndrome treated by staged intravascular embolisation and surgery.
AB  - A 28-year old Malay man with evidence of an upper motor neuron cord lesion was
      diagnosed to have a C7 to T2 spinal arterio-venous malformation and associated
      cutaneous vascular lesion. He finally agreed for treatment after 5 years of
      progressive spastic right lower limb weakness leading to inability to mobilize. A
      two staged intravascular procedure was done followed by surgery with recovery of
      ASIA impairment scale grade B.

PMID- 16898322
TI  - Atypical presentation of adult rubella.
AB  - A 55 year old female presented with fever, skin rash and subconjunctival
      hemorrhage. She also developed hepatitis. Fever and skin rash lasted for more
      than three weeks. This patient was diagnosed to have rubella, highlighting the
      fact that rubella can present with atypical features like prolonged fever and
      rash, subconjunctival hemorrhage and hepatitis, especially in adults.

PMID- 16898323
TI  - An acute pharyngeal-cervical-brachial (PCB) variant of Guillain-Barre syndrome
      presenting with isolated bulbar palsy.
AB  - Acute Guillain-Barre syndrome (GBS) is characterized by an acute onset of limb
      weakness and areflexia. There are a few rare variants that have been described
      and one of them is the pharyngeal-cervical-brachial (PCB) variant (oropharynx,
      neck, and proximal upper limb muscles). However, in this patient, the only
      presentation was bulbar involvement with fast recovery within days. This is
      likely to be the milder form of PCB that has rarely been described before. A 19
      year-old Malay lady presented with progressive dysphagia associated with nasal
      voice for one week duration. There was no limb weakness. Examination showed
      generalized areflexia. Pharyngeal and palatal muscles were markedly weak.
      Cerebrospinal fluid (CSF) examination showed raised protein level. Nerve
      conduction studies revealed generalized demyelinating motor polyneuropathy
      consistent with GBS. The patient fully recovered within three days and was
      discharged well.

PMID- 16898324
TI  - Congenital rubella syndrome with positive serology and virus isolation.
AB  - An effective live attenuated rubella vaccine was available since 1969 and
      congenital rubella syndrome can be prevented with appropriate vaccination. We
      report a baby with congenital rubella syndrome born in Klang valley to indicate
      that the Universal Rubella Vaccination Programme adopted by the Ministry of
      Health Malaysia since 2002 has yet to achieve its effect of eliminating
      transmission of rubella and preventing congenital rubella infection in the
      community. To our knowledge, the virus isolate represents the first successful
      isolation of rubella virus in this country and will serve as the reference strain
      for future comparison in molecular epidemiological tracking of rubella virus
      activity this country.

PMID- 16898326
TI  - A rare case of Von Hippel Lindau disease.
AB  - Pheochromocytoma is a rare catecholamine-secreting tumour typically arising
      within the adrenal medulla. It may occur sporadically or be associated as part of
      a tumour syndrome including Von Hippel Lindau (VHL), Multiple Endocrine Neoplasia
      (MEN) 2 and Neurofibromatosis Type 1. VHL is associated with multi-organ
      involvement of benign and malignant tumours characterized by the presence of
      retinal angiomas, hemangioblastomas of the cerebellum and spinal cord, renal cell
      carcinomas, pheochromocytomas and other cystic lesions in the kidneys, pancreas,
      and epididymis. It is a rare disorder with prevalence estimated at 2-3 per
      100,000. This case report describes a 37 years old Chinese gentleman who
      presented to our institution for further management of bilateral pheochromocytoma
      and retinal angioblastoma with problems of duodenal ulcer and anaemia. There was
      no family history of similar problems. With these features the criteria for the
      diagnosis of von Hippel Lindau disease was established.

PMID- 16898325
TI  - Mesocolic hernia: a rare cause of intestinal obstruction in childhood.
AB  - Mesocolic hernia is a rare cause of intestinal obstruction in children. The
      diagnosis involves a high index of suspicion and prompt intervention to prevent
      strangulation and a high morbidity. The embryological basis of the condition is
      of paramount importance to assist the eventual surgical correction.

PMID- 16898327
TI  - Solitary vascular malformation of the clitoris.
AB  - Isolated involvement of the clitoris by vascular malformation (VM) is very rare.
      Clinically, the lesion simulates female pseudohermaphroditism. A five-year-old
      girl presented with clitoromegaly and a clinical diagnosis of solitary VM of the
      clitoris was made. Magnetic resonance imaging showed characteristic features and
      confirmed the diagnosis and the extent of the VM. This is the first reported case
      of isolated involvement of the clitoris by VM to be diagnosed preoperatively.

PMID- 16898329
TI  - Clarithromycin induced psychosis.

PMID- 16898328
TI  - Unbalanced chromosomal translocation: a cause of recurrent spontaneous abortion.
AB  - Recurrent spontaneous abortion, defined as three consecutive abortions, occurs in
      approximately 1% to 2% of couples. Although the cause is unknown in up to 50% of
      cases, about 5% of these couples are found to be a balanced translocation
      carrier. We report a case in which the mother was identified to be a
      translocation carrier following the birth of a baby with multiple congenital
      abnormalities.

PMID- 16898331
TI  - Same day E&M services.

PMID- 16898330
TI  - Chikungunya virus infection.
AB  - Chikungunya virus (CHIKV) is a mosquito-borne alphavirus which causes epidemic
      fever, rash and polyarthralgia in Africa and Asia. Two outbreaks have been
      reported in Malaysia, in Klang, Selangor (1998) and Bagan Panchor, Perak (2006).
      It is not known if the outbreaks were caused by the recent introduction of CHIKV,
      or if the virus was already circulating in Malaysia. Seroprevalence studies from
      the 1960s suggested previous disease activity in certain parts of the country. In
      Asia, CHIKV is thought to be transmitted by the same mosquitoes as dengue, Aedes
      aegypti and Ae. albopictus. Due to similarities in clinical presentation with
      dengue, limited awareness, and a lack of laboratory diagnostic capability, CHIKV
      is probably often underdiagnosed or misdiagnosed as dengue. Treatment is
      supportive. The prognosis is generally good, although some patients experience
      chronic arthritis. With no vaccine or antiviral available, prevention and control
      depends on surveillance, early identification of outbreaks, and vector control.
      CHIKV should be borne in mind in sporadic cases, and in patients
      epidemiologically linked to ongoing local or international outbreaks or endemic
      areas.

PMID- 16898332
TI  - Look ma--no desktop.

PMID- 16898333
TI  - Are these carriers finally turning?

PMID- 16898335
TI  - Guilty.

PMID- 16898334
TI  - Are you getting through?

PMID- 16898336
TI  - A coumadin clinic helps me sleep at night.

PMID- 16898337
TI  - Joining a practice? Father knows best.

PMID- 16898338
TI  - Shopping for malpractice insurance? Learn from the experts.

PMID- 16898339
TI  - Where's primary care headed?

PMID- 16898340
TI  - Good documentation protects everyone.

PMID- 16898341
TI  - Value in health care.

PMID- 16898342
TI  - Quality is access in the Medicare prescription drug benefit--for now.

PMID- 16898344
TI  - Health care reform in Massachusetts: quality is the law's hidden jewel.

PMID- 16898343
TI  - Prevalence and economic consequences of medication adherence in diabetes: a
      systematic literature review.
AB  - A systematic literature review was conducted using a comprehensive list of
      relevant search terms (1990-2005) to identify studies on adherence among patients
      with diabetes, and its economic effect. A lack of adequate treatment adherence
      (36%-87%) among patients with diabetes was confirmed, primarily measured by
      medication possession ratio (MPR). Adherence varied among oral agent-only (36%
      87%) versus concomitant or insulin-only (54%-81%) regimens. Economic consequences
      of adherence were a decrease in health care costs, ranging from 8.6% to 28.9%,
      with an approximate 10% increase in MPR, mostly in the form of a 4.1% to 31.0%
      decrease in hospitalization. Increased cost sharing was associated with a 9% to
      23% decline in medication use.

PMID- 16898345
TI  - Is prevention too expensive?

PMID- 16898346
TI  - Managed care, consumerism, preventive medicine: does a causal connection exist?
AB  - Managed care plans, and HMOs in particular, have long touted that their emphasis
      is on preventive care, to avoid expensive illness later in life. However, few
      articles in the contemporary literature adequately address this claim. The
      available evidence seems to support that HMOs do, in fact, provide greater access
      to preventive services, but the limitations of this research are substantial.
      This article discusses the scientific evidence on the relationships between
      managed care arrangements and the implications for preventive care in the current
      era, emphasizing consumer choices and less-restrictive plan structures.

PMID- 16898347
TI  - Medication therapy management is an opportunity for pharmacy to shine--or fail.

PMID- 16898348
TI  - What is social and global justice to bioethics or bioethics to social and global
      justice?

PMID- 16898349
TI  - The ordeal of practicing care.

PMID- 16898350
TI  - Is HIPAA flawed, or unnecessary?

PMID- 16898351
TI  - Talking through your epistemological hat.

PMID- 16898352
TI  - Outing the hidden curriculum.

PMID- 16898353
TI  - Drugged.

PMID- 16898354
TI  - Congress's hybrid problem.

PMID- 16898355
TI  - What should the dean do?

PMID- 16898356
TI  - What is wrong with the Physician Charter on Professionalism.

PMID- 16898357
TI  - May doctors refuse infertility treatments to gay patients?

PMID- 16898358
TI  - Equity and population health: toward a broader bioethics agenda.
AB  - Bioethics' traditional focus on clinical relationships and exotic technologies
      has led the field away from population health, health disparities, and issues of
      justice. The result: a myopic view that misses the institutional context in which
      clinical relationships operate and can overlook factors that affect health more
      broadly than do exotic technologies. A broader bioethics agenda would take up
      unresolved questions about the distribution of health and the development of fair
      policies that affect health distribution.

PMID- 16898359
TI  - The ethics of using QI methods to improve health care quality and safety.

PMID- 16898361
TI  - Smokescreen.

PMID- 16898360
TI  - A conservative case for universal access to health care.
AB  - Universal access to health care has historically faced strident opposition from
      political conservatives in the United States, although it has long been accepted
      by most conservatives in the rest of the industrialized world. Now, in a global
      economy where American business is crippled by the rising cost of market-based
      health care, the time may be ripe for change. The key to fostering a new mindset
      among American conservatives is to show why universal access fulfills many of the
      basic values that all conservatives hold.

PMID- 16898362
TI  - Preparing for avian flu.

PMID- 16898363
TI  - Moving forward with evidence and controversies: the challenges of MDR-TB.

PMID- 16898364
TI  - Children dying from pneumonia: are we doing enough?

PMID- 16898365
TI  - Treatment of multidrug-resistant tuberculosis: evidence and controversies.
AB  - In the last decade, multidrug-resistant tuberculosis (MDR-TB, defined as
      resistance to at least isoniazid and rifampicin) has become an epidemiological
      issue of first priority at the global level. Case management needs to be
      simplified and standardised, as in many countries MDR-TB cases cannot receive
      individualised attention from specialist physicians. However, before any decision
      can be made on standardisation, a careful analysis must first be made of the
      evidence and controversies behind the various published recommendations.
      Unfortunately, the controversies outweigh the evidence. The difficulties lie not
      only in the absence of controlled trials to validate specific recommendations,
      but also in the very different and even contradictory results found in the
      literature. It is therefore essential to analyse these discrepancies before
      developing rational, uniform recommendations. The analysis should encompass the
      most essential and controversial issues regarding the management of MDR-TB
      patients: 1) confirmation of diagnosis in a suspected MDR-TB patient, and
      determination of the value of drug susceptibility testing; 2) the number of anti
      tuberculosis drugs required to treat MDR-TB; 3) the most rational use of
      effective drugs against tuberculosis; 4) the advisable length of parenteral drug
      administration or of the initial phase of treatment; 5) the contribution of
      surgery to the management of MDR-TB patients; and 6) the optimal regimen for
      treating MDR-TB: standardised vs. individualised regimens. The evidence and
      controversies regarding each of the above questions are analysed with the aim of
      facilitating decision making in the treatment of these complex patients.

PMID- 16898366
TI  - Timely diagnosis of MDR-TB under program conditions: is rapid drug susceptibility
      testing sufficient?
AB  - Timely diagnosis and effective, safe treatment are essential to reduce
      transmission and improve outcomes for patients with tuberculosis. Aside from
      laboratory methods, many programmatic factors influence the overall turnaround
      time (TAT) in diagnosing multidrug-resistant tuberculosis (MDR-TB). We measured
      each step in the overall TAT required for MDR-TB in two of five health districts
      of Lima, Peru. The total TAT, from initial sputum specimen to diagnosis and
      appropriate treatment, was 5 months, almost twice as long as the bacteriological
      procedures per se. Expensive investments in laboratory technology may yield low
      returns unless the programmatic aspects of the diagnostic process are streamlined
      at the same time.

PMID- 16898367
TI  - Impact of country of origin on drug-resistant tuberculosis among foreign-born
      persons in British Columbia.
AB  - SETTING: Provincial tuberculosis (TB) services, British Columbia, Canada.
      OBJECTIVES: To estimate the risk of drug resistance among foreign-born TB
      patients and to identify risk factors associated with drug resistance. DESIGN:
      Using the provincial TB database, we examined all culture-positive foreign-born
      TB patients for the years 1990-2001. The risk of having a drug-resistant isolate
      was estimated according to country and region of origin. RESULTS: Of 1940 foreign
      born patients identified, 247 (12.7%, 95%CI 11.3-14.3) cases had isolates
      resistant to at least one of the first-line drugs, with 160 (8.3%) isolates
      showing monoresistance, 24 (1.2%) multidrug resistance (resistance to at least
      isoniazid and rifampin) and 63 (3.3%) polyresistance (resistance to two or more
      drugs, excluding MDR). Country-specific analysis showed that immigrants from
      Vietnam (adjusted OR 2.12, 95%CI 1.37-3.27) and the Philippines (adjusted OR
      1.71, 95%CI 1.10-2.66) had a significantly higher risk of resistance than other
      immigrants. In addition, the risk was the highest for younger TB patients and
      patients with reactivated disease (adjusted OR 2.12, 95%CI 1.09-4.09).
      CONCLUSION: The risk of drug resistance was the highest among foreign-born
      patients from Vietnam and the Philippines. These findings should assist
      clinicians in prescribing and tailoring anti-tuberculosis regimens for immigrants
      more appropriately.

PMID- 16898368
TI  - Excess mortality and tuberculosis among individuals with prolonged cough: a
      population-based study from Vietnam.
AB  - SETTING: A demographic surveillance site in north-west Vietnam. OBJECTIVES: To
      compare notification rates of sputum smear-positive tuberculosis (TB) and
      mortality rates between the general population and individuals with prolonged
      cough. DESIGN: A cohort study of 559 prolonged cough cases in a total population
      of 35,832, observed over 2.5 years. Outcome measures were sputum smear-positive
      TB and death. RESULTS: The age-standardised smear-positive TB notification rate
      among cough cases (553/100,000 person-years [py], 95%CI 268-1143) was
      significantly higher than in the general population (50/100,000 py, 95%CI 43-57),
      with a relative risk of 11.06 (95%CI 8.28-14.77). Among those who had a chest X
      ray suggestive of TB but negative sputum smears prior to the study start, the
      rate was 6542/100,000 py (95%CI 2906-12,511). The cough cohort had a 2.61 (95%CI
      2.38-2.87) times higher risk of dying than the general population. CONCLUSIONS:
      Individuals with prolonged cough in this study run a significantly increased risk
      of developing infectious TB and of dying. We recommend further evaluations of
      improved follow-up systems aimed at identifying and treating sputum smear
      negative TB cases before they convert to an infectious stage.

PMID- 16898369
TI  - Causes of death during tuberculosis treatment in Tomsk Oblast, Russia.
AB  - SETTING: Tuberculosis (TB) incidence and mortality in Russia have risen
      dramatically over the past 15 years. OBJECTIVE: To identify risk factors and
      causes of death among TB patients in Russia. DESIGN: A retrospective study
      conducted to determine the risk factors and causes of death in patients receiving
      TB therapy in Tomsk, Siberia. RESULTS: Of 1916 patients who initiated treatment
      between 1 January 2002 and 31 December 2003, 183 (9.6%) died during treatment, 38
      (21%) in the first week of therapy. Twenty-five per cent of deaths were not
      directly attributable to TB. Risk factors for death included older age, previous
      treatment for TB, multidrug resistance and alcoholism. CONCLUSIONS: The high
      death rate during TB treatment observed in this cohort likely reflects an
      increased risk of dying not only from TB, but also from comorbid conditions, such
      as alcoholism and cardiovascular disease. Overall, alcoholism and late
      presentation both contributed substantially to the mortality in this cohort.

PMID- 16898370
TI  - Tuberculosis treatment default among Brazilian children.
AB  - OBJECTIVES: To study the prevalence and time of tuberculosis (TB) treatment
      default among children and to compare defaulters with those who completed
      treatment. METHODS: Retrospective cohort study at the Hospital Municipal Jesus,
      Rio de Janeiro, Brazil, among TB patients aged <15 years followed from 1998 to
      2002. The group that completed treatment was compared with those that defaulted.
      RESULTS: The records of 248 patients were studied. The default rate was 24.2% and
      was more frequent in the first 2 months of treatment (43.3%) and among those aged
      <1 year (42.4%). The following variables were associated with default: previous
      default (relative risk [RR] 1.99, 95%CI 1.12-3.54, P = 0.035), father not living
      with the child (RR 1.85, 95%CI 1.06-3.21, P = 0.030) and father using illicit
      drugs (RR 2.93, 95%CI 1.44-5.97, P = 0.002). CONCLUSIONS: Health professionals
      responsible for treating children with TB should pay special attention to
      children aged <1 year, those with a history of previous default, and those whose
      father is absent or an illicit drug user.

PMID- 16898371
TI  - Situation analysis of TB microscopy centres in Ghana.
AB  - SETTING: Public health laboratories in Ghana performing tuberculosis (TB)
      microscopy. OBJECTIVE: To assess the situation of the laboratories in terms of
      staff strength, technical skills, documentation, biosafety practices, equipment,
      supplies and disposal systems. DESIGN: Methods used for data collection were
      interviews using a structured questionnaire, informal observation of laboratory
      registers, disposal systems and safety measures for sputum handling. RESULTS: Of
      114 laboratories visited between 2000 and 2001, 102 (89.5%) were performing TB
      microscopy. Of the staff working in the laboratories, 9% were medical
      technologists, 24% laboratory technicians, 37% laboratory assistants and 30%
      orderlies. Average false-negative and -positive rates were respectively 13% and
      14%. Although most of the centres (85.3%) were using the recommended TB
      laboratory register for recording, in most cases they were not filled in
      accurately or completely. The majority of the available microscopes had
      mechanical or optical faults. Availability of other materials for smear
      preparation and staining ranged from 44% to 82%. The main methods employed for
      disposal of laboratory waste were burning and burying, but conditions were poor
      in most of the facilities visited. CONCLUSION: Training of laboratory personnel
      in TB microscopy and establishment of a quality assurance system are needed in
      Ghana.

PMID- 16898372
TI  - An evaluation of symptom and chest radiographic screening in tuberculosis
      prevalence surveys.
AB  - SETTING: A tuberculosis (TB) prevalence survey was performed in 2002 in two urban
      communities in Cape Town, South Africa. The population was 36,334 in 2001, and
      the TB notification rate was 341 per 100,000 population for new smear-positive TB
      in 2002. OBJECTIVE: To evaluate the relative contributions of symptom and chest
      radiographic (CXR) screening in the detection of subjects with smear- and/or
      culture-positive TB in prevalence surveys. DESIGN: Information on symptoms, CXR
      abnormalities, sputum smear and culture was gathered from a random cluster sample
      of 1170 adults (aged > or = 15 years). Smear and/or culture-positive TB was used
      as the gold standard. RESULTS: Of 1170 adults, 29 had bacteriologically positive
      TB (smear- and/or culture-positive). The presence of any abnormalities on CXR had
      the highest sensitivity for detecting subjects with bacteriologically positive TB
      (0.97, 95%CI 0.90-1.00). Specificity for any abnormalities on CXR was 0.67 (95%CI
      0.64-0.70). The specificity of any of five TB-related symptoms was 0.68 (95%CI
      0.65-0.71). Individual symptoms had low sensitivities, ranging from 0.10 for
      fever to 0.54 for cough of > or = 2 weeks. CONCLUSION: In this TB prevalence
      survey, CXR screening, but not symptom screening, was a sensitive alternative to
      sputum examination of all participants.

PMID- 16898373
TI  - Tuberculin reactivity in bacille Calmette-Guerin vaccinated populations: a
      compilation of international data.
AB  - SETTING: The effect of previously administered bacille Calmette-Guerin (BCG)
      vaccine on subsequent tuberculin skin tests (TSTs) complicates screening for
      latent tuberculosis infection (LTBI) in foreign-born persons. OBJECTIVE: To
      determine the usefulness of the TST as a screening test for LTBI in foreign-born
      persons. DESIGN: A literature search was performed of published studies that
      compared tuberculin reactivity amongst BCG-vaccinated and non-vaccinated groups.
      The percentages of positive reactors in the two groups were then used to
      calculate a prevalence ratio. RESULTS: The prevalence ratio varied with the age
      of the groups tested and the incidence of TB in their countries of origin. The
      TST performed poorly in vaccinated persons of all ages from countries of low TB
      incidence, but was a useful screen for LTBI in vaccinated adults from countries
      of high and intermediate incidence. The test performed poorly as a screening
      method for vaccinated children under 2 years of age. Its usefulness in vaccinated
      children aged 2-14 years varied considerably. CONCLUSIONS: The usefulness of the
      TST as a screening method for LTBI depends on the age of the patient and the
      incidence of TB in their country of origin.

PMID- 16898375
TI  - Preparation of mycobacteria-containing artificial sputum for TB panel testing and
      microscopy of sputum smears.
AB  - SETTING: Panel testing, blinded cross rechecking and on-site evaluation are the
      three methods for external quality assessment (EQA) of acid-fast bacilli (AFB)
      smear microscopy. Panel testing can provide data on laboratory capabilities prior
      to implementing a rechecking programme, assess the current status of laboratory
      performance and detect problems associated with diagnostic performance. Thus far,
      two methods for preparing panel test slides have been reported: these use real
      AFB-positive and -negative sputum treated with sodium hydroxide (NaOH) or N
      acetyl-L-cysteine (NALC). OBJECTIVE: To evaluate the above methods and to develop
      a new method to prepare panel test slides with artificial sputum. DESIGN: Panel
      test slides were prepared using the NaOH and NALC methods. New artificial sputum
      preparation methods were developed and examined using a cultured monocyte cell
      line, cultured avirulent mycobacteria and methylcellulose or polyacrylamide gel
      as substrate. Smears prepared by the four methods were compared. RESULTS: Panel
      test slides prepared with NaOH and NALC methods are not macroscopically or
      microscopically similar to real smears. Our new artificial sputum is similar to
      real sputum in viscosity and macroscopic and microscopic appearance; it is also
      consistent in panel positivity grades. CONCLUSION: The artificial sputum
      described here could contribute to the EQA and training in tuberculosis
      laboratories or microscopy centres.

PMID- 16898374
TI  - Prevalence and determinants of positive tuberculin reactions of residents in old
      age homes in Hong Kong.
AB  - OBJECTIVE: To determine the prevalence of tuberculous infection and the
      predictors of positive tuberculin reactivity in old age home residents in Hong
      Kong. DESIGN: Cross-sectional study. METHODS: A questionnaire-interview and
      review of medical records were carried out, together with measurement of weight
      and height/arm span and assessment of nutritional status. A one-stage tuberculin
      skin test (TST) was performed using two units of PPD RT23. An induration > or =
      10 mm was considered as positive. RESULTS: Of 3682 residents (71.7%
      participation, mean age 82 years) who agreed to undergo a TST, 46.3% had a
      positive reaction. Factors associated with a significantly higher risk of a
      positive TST included being male, an ex- or current smoker and having a past
      history of tuberculosis (TB). Factors associated with reduced positive tuberculin
      reactivity included older age groups (> 70 years), a history of cancer and
      chronic obstructive pulmonary disease and low body mass index quartiles.
      CONCLUSION: In old age homes, the high prevalence of latent tuberculous infection
      is responsible for the high rate of active TB due to reactivation. Early
      diagnosis and treatment are necessary to prevent transmission of disease in these
      crowded environments with susceptible individuals.

PMID- 16898376
TI  - Method for efficient storage and transportation of sputum specimens for molecular
      testing of tuberculosis.
AB  - SETTING: The polymerase chain reaction (PCR) is a highly sensitive method for the
      detection of Mycobacterium tuberculosis and is available in most countries,
      though to a lesser extent in rural areas. OBJECTIVE: To amplify M. tuberculosis
      DNA sequences of sputum spotted on FTA cards and compare them with the results of
      microscopic examination among culture-positive samples. DESIGN: A total of 102
      sputum specimens of TB patients in treatment were spotted on FTA cards and stored
      at room temperature until DNA analysis. We assessed the IS6110 region of M.
      tuberculosis. The efficacy of the PCR assay for the direct detection of M.
      tuberculosis was evaluated and compared with the results of cultures (Middlebrook
      7H9 broth) and smears of fresh sputum specimens. RESULTS: We were able to detect
      10 fg/microl of mycobacterial DNA even after 6 months in storage. The PCR
      sensitivity and specificity using the FTA card system were 82% and 96%, while
      microscopic examination showed 41% and 95%, respectively. CONCLUSION: The FTA
      card system for the storage of bacterial DNA from sputum samples should be
      considered for the molecular diagnosis of tuberculosis. Samples can easily be
      obtained from geographically isolated populations and shipped by mail for
      accurate molecular diagnosis.

PMID- 16898377
TI  - Treatment outcome of asthma after one year follow-up in health centres of several
      developing countries.
AB  - SETTING: Seven selected out-patient clinics caring for asthma patients in
      Algeria, Guinea, Morocco, Syria, Turkey and Vietnam. DESIGN: Evaluation of
      treatment outcomes after one year of follow-up of a cohort of asthma patients
      consecutively enrolled in a prospective study evaluating routine practice.
      RESULTS: Among 310 asthma patients registered, the following outcomes were
      recorded after one year of follow-up: 95 (31%) successful, 61 (20%) under
      control, 35 (11%) failed, 116 (37%) defaulted and 3 (1%) transferred. Among the
      167 (53.9%) patients still on treatment after one year there was a substantial
      increase in the proportion of patients classified as intermittent at the end of
      treatment (from 11% to 53%), with a decrease in all categories of persistent
      asthma (from 34% to 12% for mild, 45% to 28% for moderate and 10% to 8% for
      severe asthma). CONCLUSIONS: While patients' quality of life can be improved if
      they follow regular treatment, the key challenge in providing care is to ensure
      that patients adhere to their treatment.

PMID- 16898378
TI  - Smoking patterns and predictors of smoking cessation in elderly populations in
      Lebanon.
AB  - OBJECTIVE: To investigate smoking patterns in an elderly, low-income population
      and to identify predictors of smoking cessation, in addition to analyzing the
      importance of smoking in relation to other risk factors for hospitalization.
      DESIGN: The data were part of an urban health study conducted among 740
      individuals aged > or = 60 years in three suburban communities of low socio
      economic status in Beirut, one of them a refugee camp. A detailed interview
      schedule was administered that included comprehensive social and health
      information. RESULTS: The overall prevalence of current smokers was 28.1%. Almost
      half of the group were ever smokers, of whom 44% had quit smoking when they
      experienced negative health effects. Having at least one chronic illness and
      having a functional disability significantly increased the odds of smoking
      cessation. In addition, being a former smoker increased the likelihood of
      hospital admission. CONCLUSIONS: This study is of particular importance, as it
      has implications for similar low-income and refugee communities in the region and
      elsewhere. There is a need for more concerted efforts by public health officials
      to target elderly individuals as a group for smoking cessation interventions,
      particularly now that mortality and health benefits have been well documented.

PMID- 16898379
TI  - Can WHO therapy failure criteria for non-severe pneumonia be improved in children
      aged 2-59 months?
AB  - SETTING: In the recent past, there have been reports of rising treatment failure
      rates for non-severe pneumonia. It is felt that World Health Organization (WHO)
      criteria for therapy failure are too sensitive and that many children are
      unnecessarily classified as failures. We studied alternative, less sensitive
      therapy failure criteria. METHODS: In this nested study we followed the clinical
      course of non-severe pneumonia in children aged 2-59 months using alternative
      therapy failure criteria. All children received amoxicillin and were followed up
      on days 3, 5 and 14 after enrollment. On day 3, children were labelled as therapy
      failure only if their condition had deteriorated. These failure rates were
      compared with those using WHO definitions. RESULTS: During the study period, 876
      children with non-severe pneumonia were followed up until day 14. On day 3, using
      alternative therapy failure criteria, 31 (3.5%) children were labelled as therapy
      failure compared to 95 (10.8%) using current WHO criteria. The difference was
      statistically significant (P = 0.001). CONCLUSIONS: The alternative therapy
      failure criteria work reasonably well, without causing any higher risk to
      children with non-severe pneumonia. Antibiotics should be changed only in those
      children who show signs of deterioration on day 3. This would prevent unnecessary
      changes in antibiotic treatment in many children.

PMID- 16898380
TI  - Response to cotrimoxazole in the management of childhood pneumonia in first-level
      health care facilities.
AB  - BACKGROUND: Reports of high levels of antimicrobial resistance to cotrimoxazole
      in children with non-severe pneumonia (NSP) have prompted calls for a change to
      amoxicillin in the therapeutic guidelines at the first-level health care facility
      (FLHF). FLHFs lack data about the use of World Health Organization (WHO) acute
      respiratory infection (ARI) standard case management (SCM). OBJECTIVE: To apply
      ARI SCM guidelines at the FLHF, assess clinical outcome of NSP with oral
      cotrimoxazole and determine the risk factors influencing treatment outcome.
      DESIGN: Health care workers (HCWs) at 14 health centres managed children aged 2
      59 months with NSP according to ARI SCM guidelines. The primary outcome was
      treatment failure, including change of antibiotic therapy and loss to follow-up.
      RESULTS: Of 949 children enrolled, 110 (11.6%) failed therapy with oral
      cotrimoxazole. Clinical failure was significantly higher among children
      presenting with a fast respiratory rate of > or = 15 breaths/min above normal for
      age and wheezing on examination. CONCLUSIONS: To treat children with NSP at the
      FLHF, oral cotrimoxazole is an acceptable treatment choice in view of the
      efficacy, cost and ease of use. In children with wheezing and signs of pneumonia,
      the decision to use antibiotic therapy should be made after a trial of
      bronchodilator therapy.

PMID- 16898381
TI  - Results of a tuberculosis-specific IFN-gamma assay in children at high risk for
      tuberculosis infection.
AB  - The specificity of the tuberculin skin test (TST) for the diagnosis of latent
      tuberculosis infection (LTBI) is adversely affected by bacille Calmette-Guerin
      (BCG) vaccination and infection with non-tuberculous mycobacteria. Interferon
      gamma release assays (IGRAs) using TB-specific antigens promise higher
      specificity. We compared a new IGRA and TST in 184 schoolchildren at high risk
      for LTBI. The IGRA and TST were positive in 33.2% and 43.5% of the children,
      respectively (P < 0.001). If studies confirm that this difference is due to
      higher specificity of this IGRA, it may have an important role to play in the
      diagnosis of LTBI and identification of children at true risk for TB.

PMID- 16898382
TI  - Discordance between tuberculin skin test and interferon-gamma assays.

PMID- 16898383
TI  - Co-existing sarcoidosis and autoimmune pernicious anaemia: a rare combination.

PMID- 16898384
TI  - New diagnostic options in tuberculous meningitis?

PMID- 16898385
TI  - Controlling patient expectations: important in maximizing patient satisfaction.

PMID- 16898386
TI  - Transpupillary thermotherapy with indocyanine green dye enhancement for the
      treatment of occult subfoveal choroidal neovascularization in age-related macular
      degeneration.
AB  - BACKGROUND AND OBJECTIVES: Transpupillary thermotherapy (TTT) with indocyanine
      green (ICG) dye enhancement (TTT+) and TTT alone were compared for safety and
      effectiveness as a treatment of occult subfoveal choroidal neovascularization in
      age-related macular degeneration. PATIENTS AND METHODS: Twenty-one patients were
      randomized to receive TTT (12 eyes) or TTT+ (9 eyes) and observed for at least 6
      months. ETDRS visual acuity and fluorescein and ICG angiography were obtained
      every 3 months. RESULTS: The median initial visual acuity was 20/80 in the TTT
      group and 20/100 in the TTT+ group. At 6 months, loss of less than 3 lines of
      visual acuity was present in 7 of 12 eyes (58%) in the TTT group and 5 of 9 eyes
      (56%) in the TTT+ group. At the final examination, there was no active choroidal
      neovascularization exudation in 6 of 12 eyes (50%) in the TTT group and 5 of 9
      eyes (56%) in the TTT+ group. The median final visual acuity was 20/125 in the
      TTT group and 20/160 in the TTT+ group. Ocular or systemic complications were not
      encountered in either group. CONCLUSION: TTT with ICG dye enhancement was as safe
      and effective as TTT alone in this study. However, modifications of treatment
      protocol would be needed to see whether there is any advantage to using ICG dye
      enhancement.

PMID- 16898387
TI  - Photodynamic therapy for choroidal neovascularization associated with submacular
      hemorrhage in age-related macular degeneration.
AB  - BACKGROUND AND OBJECTIVE: To describe visual acuity results after photodynamic
      therapy (PDT) with verteporfin for choroidal neovascularization in age-related
      macular degeneration (AMD) associated with large submacular hemorrhage (SMH).
      PATIENTS AND METHODS: Eyes that had AMD, at least 12 months' follow-up, and SMH
      of at least 2.5 mm2, and had received no other treatment modality in conjunction
      with PDT, were divided into two groups: eyes with spontaneous SMH that was
      treated with PDT and eyes with SMH that occurred following PDT treatment. The
      presence of SMH did not preclude the patients from undergoing further PDT.
      RESULTS: Mean acuity of the spontaneous SMH group was 20/294 initially and 20/252
      after 12 months. Mean acuity of the post-PDT SMH group was 20/336 initially and
      20/406 after 12 months. Initial and 12-month acuities in both groups were not
      statistically different. Mean size of the hemorrhage was 11.5 mm2 in the
      spontaneous SMH group and 17.8 mm2 in the post-PDT SMH group. Subgroup analysis
      showed no statistically significant difference between initial and final visual
      acuities, regardless of the presence of blood under the fovea. Analysis by size
      of the SMH showed only the spontaneous SMH group with hemorrhages over 10 mm2 to
      have a statistically significant difference in visual acuity at 12 months (P=
      .0001; initial acuity, 20/230; 12-month acuity, 20/456). CONCLUSION: Eyes treated
      with PDT for choroidal neovascularization associated with submacular hemorrhage
      and AMD maintained stable vision over 12 months.

PMID- 16898389
TI  - A combined technique for surgical repair of Descemet's membrane detachments.
AB  - BACKGROUND AND OBJECTIVE: Descemet's membrane detachments are an uncommon
      complication after cataract surgery that can result in severe visual loss. A
      combined technique of intracameral gas injection and transcorneal suturing for
      the repair of Descemet's membrane detachments is described. PATIENTS AND METHODS:
      In this interventional case series, four cases of Descemet's membrane detachments
      with associated corneal edema observed following cataract surgery were
      successfully repaired using a combined technique of intracameral gas injection
      and transcorneal suturing. RESULTS: In all cases, Descemet's membranes were
      successfully reattached using the aforementioned technique. In three cases, the
      associated corneal edema resolved postoperatively. In the fourth case, the
      patient required a penetrating keratoplasty for persistent corneal edema despite
      immediate anatomical success following reattachment. CONCLUSIONS: Combined
      intracameral gas and transcorneal suturing appears to be an effective technique
      in the repair of Descemet's membrane detachments. Early intervention may prevent
      persistent or recurrent corneal edema.

PMID- 16898388
TI  - Clinical manifestations and treatment outcome of optic neuropathy in thyroid
      related orbitopathy.
AB  - BACKGROUND AND OBJECTIVE: To investigate the incidence and outcome of optic
      neuropathy associated with thyroid-related orbitopathy. PATIENTS AND METHODS: All
      patients diagnosed as having optic neuropathy associated with thyroid-related
      orbitopathy who underwent treatment for optic neuropathy between January 1, 1999,
      and March 1, 2003, were reviewed. Demographic and clinical data were extracted
      from the oculoplastic registry (electronic medical record). RESULTS: Optic
      neuropathy occurred in 20 of 595 patients with thyroid-related orbitopathy
      (3.4%). All patients received systemic steroids, 7 patients received orbital
      steroid injections, and 2 patients were treated with orbital radiotherapy.
      Orbital decompression was performed in all 26 orbits. Visual acuity improved from
      a mean of 20/150 to 20/30 (P < .001). Color vision improved from a mean of 5.2/14
      to 11/14 (P = .001). The afferent pupillary defect disappeared shortly after
      treatment for all but 1 case, and improved in all cases. Exophthalmos decreased
      from 26.4 +/- 2.5 to 21.5 +/- 2.1 mm (P< .001; 95% confidence interval, 3.8 to
      5.7). CONCLUSIONS: Optic neuropathy manifests rarely in patients with thyroid
      related orbitopathy. Monitoring visual acuity or afferent pupillary response may
      be a reliable way of assessing and monitoring optic neuropathy. In this study,
      patients had improved visual acuity and optic nerve function after a combination
      of medical and surgical treatment.

PMID- 16898390
TI  - A comparative study for mesopic contrast sensitivity between photorefractive
      keratectomy and laser in situ keratomileusis.
AB  - BACKGROUND AND OBJECTIVE: To compare the effect on visual performance of
      photorefractive keratectomy (PRK) and laser in situ keratomileusis (LASIK) with
      mesopic contrast sensitivity. PATIENTS AND METHODS: Postoperative visual
      performance for 40 eyes undergoing PRK and 40 eyes undergoing LASIK was compared
      with mesopic contrast sensitivity at 1, 3, and 6 months postoperatively. Eyes
      were divided into two groups (< -6.0 D and > -6.25 D). Mesopic contrast
      sensitivity was performed with the patient's best-corrected visual acuity of
      20/20 or better under photopic conditions. RESULTS: A significant decrease in
      mesopic contrast sensitivity from preoperative baseline was obtained at all
      spatial frequencies for the PRK and LASIK groups (P < .05). There was no
      statistically significant difference at 1 or 3 months postoperatively in both
      groups (P > .05). At 6 months postoperatively, LASIK significantly decreased
      mesopic contrast sensitivity more than PRK in myopia with a refractive error of
      less than -6.0 D, especially at the middle and high spatial frequencies of 6, 9,
      and 12 cycles per degree (P < .05). However, no statistically significant
      differences in mesopic contrast sensitivity between PRK and LASIK were found in
      myopia with a refractive error of greater than -6.25 D (P > .05). CONCLUSIONS: In
      broad-beam excimer laser refractive surgery, PRK seemed to have a more
      significant effect on mesopic contrast sensitivity than LASIK for myopia with a
      refractive error of less than -6.0 D at 6 months postoperatively.

PMID- 16898391
TI  - In vivo laser confocal microscopic analysis of human corneal epithelial sheet
      cultured on amniotic membrane.
AB  - BACKGROUND AND OBJECTIVE: Corneal epithelial sheet cultured on amniotic membrane
      ex vivo has been developed for the treatment of severe ocular surface disorders.
      In this study, human corneal epithelial sheets cultured on amniotic membranes
      were analyzed using a laser scanning confocal microscope. MATERIALS AND METHODS:
      Human corneal epithelial cells were cultured on four sheets of amniotic membrane,
      and they were examined layer by layer using the laser scanning confocal
      microscope. RESULTS: The superficial layer cells were mosaic in appearance. In
      the superficial layer, focal areas of slender and elongated cells were noted. In
      addition, highly reflective materials were noted. Basal epithelial cells of the
      corneal epithelium sheet at a slightly deeper plane displayed mosaic pattern with
      smaller cells. At a slightly deeper plane, the basement membrane of amnion showed
      relatively bright homogeneity. CONCLUSION: The laser scanning confocal microscope
      can examine the morphology of human corneal epithelial cells cultured on amniotic
      membranes.

PMID- 16898392
TI  - Fusarium endophthalmitis following keratitis associated with contact lenses.
AB  - A recent outbreak of fungal keratitis associated with contact lens use has been
      reported. During the past 4 months, a total of 36 patients with Fusarium
      keratitis have presented to one medical center. Two cases of Fusarium
      endophthalmitis resulting from this series of fungal keratitis associated with
      soft contact lens wear are described.

PMID- 16898393
TI  - Delayed posttraumatic Propionibacterium acnes endophthalmitis in a child.
AB  - A 7-year-old boy presented with granulomatous anterior uveitis after an
      unrecognized penetrating injury in the same eye 2 months previously. The uveitis
      was unresponsive to topical corticosteroid therapy, lensectomy with anterior
      vitrectomy, and administration of intraocular and subconjunctival injections of
      vancomycin. Pars plana vitrectomy, capsulectomy, and injection of intravitreal
      vancomycin were eventually performed, leading to complete resolution of the
      intraocular inflammation. Culture and histopathologic examination of a capsular
      specimen confirmed sequestered Propionibacterium acnes infection. This case
      demonstrates that P. acnes may cause delayed endophthalmitis following
      penetrating trauma and may persist within capsular remnants in the aphakic eye.

PMID- 16898394
TI  - Hypopyon and pseudoendophthalmitis associated with chronic vitreous hemorrhage.
AB  - Infectious endophthalmitis is an uncommon but potentially devastating eye
      disease. Although the presence of a hypopyon is considered one of the hallmark
      clinical signs of infectious endophthalmitis, hypopyon associated with non
      infectious causes may occur. Two patients with hypopyon and pseudoendophthalmitis
      secondary to chronic vitreous hemorrhage are described. In both cases, the
      hypopyon improved without the use of intravitreal antibiotics.

PMID- 16898395
TI  - Uveal metastases from breast carcinoma in three male patients.
AB  - The authors present a case series of three male patients with uveal metastases
      originating from breast carcinoma. The mean age at discovery of uveal metastases
      and the mean interval from diagnosis of primary breast carcinoma were 49.7 and
      2.3 years, respectively. The analogous data in women are 56 and 5.4 years,
      respectively. In this series, all three patients were affected bilaterally and
      four of six eyes (67%) had multifocal tumors. In women, metastases are bilateral
      in 38% and multifocal in 48%. Compared with women, metastases in men may occur
      sooner and with a higher incidence of bilateral and multifocal tumors.

PMID- 16898396
TI  - Upper eyelid extension of a filtering bleb following glaucoma shunt surgery.
AB  - The authors describe a case of a filtering bleb that extended into the eyelid of
      a 71-year-old man following glaucoma surgery with a shunt implant. The patient
      presented with a left upper eyelid mass and had ocular surface and mechanical
      sequelae. Computed tomography scan demonstrated a fistula between the original
      filtering tract and the eyelid, creating an inadvertent filtering bleb. Cytology
      revealed fluid consistent with aqueous humor. Intraocular pressure remained
      normal and symptoms improved with conservative management. The patient deferred
      any surgical revision. Glaucoma tube shunts may lead to ocular and rare orbital
      complications from inadvertent bleb extension, as seen in this case.

PMID- 16898397
TI  - Corneal perforation during laser blepharoplasty.
AB  - A 61-year-old woman presented with photophobia, pain, epiphora, and decreased
      vision as a result of two iatrogenic corneal perforations sustained during carbon
      dioxide laser blepharoplasty. The management and course of the case are outlined.
      Laser blepharoplasty complications are reviewed. This case highlights the
      potential occurrence of corneal penetration with laser blepharoplasty. Meticulous
      awareness of the laser effects on periocular tissue must be kept in mind at all
      times during laser blepharoplasty to avoid unnecessary intraocular side effects
      and undesirable postoperative outcomes.

PMID- 16898398
TI  - Neodymium:YAG laser peripheral iridotomy: cause of a visually incapacitating
      cataract?
AB  - Neodymium:YAG (Nd:YAG) laser peripheral iridotomy is the procedure of choice to
      treat and avoid further episodes of angle-closure glaucoma. A patient who
      developed a visually incapacitating posterior subcapsular lens opacity shortly
      after Nd:YAG laser peripheral iridotomy is described. The patient underwent
      cataract surgery and achieved a good level of visual acuity postoperatively. The
      intraocular pressure remained under control with no medical treatment. This case
      suggests a possible, albeit rare, potential complication of Nd:YAG laser
      peripheral iridotomy.

PMID- 16898399
TI  - Optical coherence tomography findings in ocular decompression retinopathy.
AB  - Three days following trabeculectomy surgery, a 47-year-old woman experienced a
      decline in visual acuity to 20/400. Fundus findings were consistent with
      decompression retinopathy, and optical coherence tomography revealed macular
      thickening, cystoid macular edema, and neurosensory macular detachment. The
      foveal anatomy normalized following topical treatment, and visual acuity returned
      to 20/30 by 10 weeks postoperatively. Both macular detachment and cystoid macular
      edema may contribute to acute decline in visual acuity in decompression
      retinopathy. Optical coherence tomography facilitated the prompt detection of
      treatable pathology, which resolved following appropriate medical therapy.

PMID- 16898400
TI  - Influence of myelinated retinal nerve fibers on scanning laser polarimetry using
      variable and enhanced corneal compensation methods.
AB  - Five eyes with myelinated retinal nerve fibers were imaged using a scanning laser
      polarimeter with variable corneal compensation and with enhanced corneal
      compensation (a new research software). Using variable corneal compensation,
      areas of myelinated retinal nerve fibers uniformly appeared as areas of increased
      retardation. Using enhanced corneal compensation software, the same myelinated
      retinal nerve fiber areas adjacent to the optic nerve head appeared as areas of
      clinically significant thinning of the retinal nerve fiber layer in the superior
      and inferior quadrants, and as areas of increased retinal nerve fiber layer
      thickness nasally and temporally. Wedge-shaped myelinated retinal nerve fibers
      along a retinal nerve fiber bundle and discontinuous to the optic nerve head
      caused increased retardation with both compensation methods. The results show
      that influence of myelinated retinal nerve fibers on scanning laser polarimetric
      results varies according to the compensation method and the retinal location of
      the myelinated retinal nerve fibers.

PMID- 16898401
TI  - Enucleated eye model for intraocular retinal prosthesis implantation.
AB  - An enucleated porcine eye model was developed to assess intraocular retinal
      prosthesis implantation surgery. The surgical technique consists of corneal and
      crystalline lens removal, keratoprosthesis replacement, and vitrectomy. To test
      the eye model, the scleral incision was increased to 5 mm and a 10-mm wide
      retinal prosthesis folded and inserted. One retinal tack was used to fix the
      prosthesis to the retina. A retinal prosthesis array was inserted without
      significant damage to the array and conformed to the curvature of the eye. Fundus
      photography and optical coherence tomography were performed at the end of
      surgery.

PMID- 16898402
TI  - Artificial tear gel as a gonioscopic and contact lens ophthalmoscopy fluid.
AB  - An easy and convenient method of using a commercially available clear lubricant
      eye gel for diagnostic and therapeutic contact lens applications at the slit lamp
      is described. The authors used hydroxypropyl methylcellulose 0.3% as a medium for
      contact lens applications and compared it to the traditional hydroxypropyl
      methylcellulose 2.5%. Hydroxypropyl methylcellulose 0.3% as a contact lens
      solution is clear, viscous, and easy to apply; does not require irrigation after
      use; and has levels of convenience, safety, and visual recovery superior to the
      standard 2.5% solution characteristics. The 0.3% gel could be used as an
      effective and convenient gonioscopic and ophthalmoscopic contact medium.

PMID- 16898403
TI  - Surface rendering of 3D ultrasound images in ophthalmology.
AB  - Surface rendering of three-dimensional ultrasound images is a novel way of
      imaging ophthalmic pathologies in vivo. The authors have evaluated surface
      rendering of three-dimensional ultrasound images in selected cases of opthalmic
      disease.

PMID- 16898404
TI  - Freedom of information. Technology unites new hospital campus.

PMID- 16898405
TI  - Position of power. Using an EPMS to provide electricity savings, reliability and
      other benefits.

PMID- 16898406
TI  - Inside information. Developing an effective design program.

PMID- 16898407
TI  - Project pitfalls. Nine common hospital planning mistakes.

PMID- 16898408
TI  - Getting ready. New JCAHO standard aims to test hospital emergency response.

PMID- 16898409
TI  - Piling up the points. An operations exec tells how her hospital's ES department
      improved its satisfaction scores.

PMID- 16898410
TI  - Synthesis of poly d(G-C) oligonucleotides.
AB  - Model sequences for evaluation of the GC dimer sequence repetition on synthesis
      success were prepared and analyzed by HPLC. Contiguous d(G-C) or d(C-G) sequences
      have a deleterious effect on DNA oligonucleotide synthesis. The critical number
      seems to be about 6 GCs in a row. If the GCs are separated by other nucleotides,
      the effect is not as severe.

PMID- 16898411
TI  - A simple and efficient synthesis of puromycin, 2,2'-anhydro-pyrimidine
      nucleosides, cytidines and 2',3'-anhydroadenosine from 3',5'-O-sulfinyl xylo
      nucleosides.
AB  - Synthesis of antibiotics, puromycin and 3'-amino-3'-deoxy-N6,N6-dimethyladenosine
      11 was achieved by utilizing the cyclic sulfite 6a of the xylo-3',5'-dihydroxy
      group as a new protective group. The key synthetic step is the deprotection of
      the sulfite moiety through the intramolecular cyclization of 2-alpha-carbamate 7.
      In a similar manner 2,2'-anhydro-pyrimidine nucleosides 15, ribo-cytidines 17 and
      2',3'-anhydroadenosine 14 were prepared in high yields from the corresponding
      sulfites 4, 5, and 6b, respectively.

PMID- 16898412
TI  - Preparation of a fludarabine intermediate via selective alkylation of 2
      fluoroadenine.
AB  - The reaction between 2-fluoroadenine (3) and 1,3,5-tri-O-benzyl-1-alpha-D
      chloroarabinofuranose (4) with potassium t-amylate was evaluated in various
      solvents to afford 9-beta-D-(2,3,5-tri-O-benzyl-arabinofuranosyl)-2-fluoroadenine
      (5) and the corresponding alpha-anomer (6). In addition, 7-beta-D-(2,3,5-tri-O
      benzyl-arabinofuranosyl)-2-fluoroadenine (7) and an unusual "bis-fluoroadenine"
      nucleoside (8) were isolated as byproducts. The highest anomeric ratio
      (beta/alpha > 10) and conversion (> 80%) were observed with the highly polar
      solvent sulfolane. This reaction was demonstrated on gram scale as a practical
      laboratory synthesis of 5, a known intermediate in the synthesis of fludarabine.

PMID- 16898413
TI  - Unique 31P spectral response to the formation of a specific restriction enzyme
      DNA complex.
AB  - Protein-induced distortion is a dramatic but not universally observed feature of
      sequence-specific DNA interactions. This is illustrated by the crystal structures
      of restriction enzyme-DNA complexes: While some of these structures exhibit DNA
      distortion, others do not. Among the latter is Pvull endonuclease, a small enzyme
      that is also amenable to NMR spectroscopic studies. Here 31P NMR spectroscopy is
      applied to demonstrate the unique spectral response of DNA to sequence-specific
      protein interactions. The 31P NMR spectrum of a noncognate DNA exhibits only
      spectral broadening upon the addition of enzyme. However, when enzyme is added to
      target DNA, a number of 31P resonances shift dramatically. The magnitudes of the
      chemical shifts (2-3 ppm) are among the largest observed. Site-specific
      substitution with phosphoramidates and phosphorothioates are used analyze these
      effects. While such spectral features have been interpreted as indicative of DNA
      backbone distortions, FRET analysis indicates that this does not occur in PvuII
      cognate DNA complexes in solution. The distinct 31P spectral signature observed
      for cognate DNA mirrors that observed for the enzyme, underscoring the unique
      features of cognate complex formation.

PMID- 16898414
TI  - Efficient large-scale synthesis of 5'-O-dimethoxytrityl-N4-benzoyl-5-methyl-2'
      deoxycytidine.
AB  - An efficient process to synthesize 5'-O-dimethoxytrityl-N4-benzoyl-5-methyl-2'
      deoxycytidine in high yield and quality is described. Final benzoylation was
      improved by developing a method to selectively hydrolyze benzoyl ester
      impurities. This inexpensive approach was scaled up to multikilogram quantities
      for routine use in oligonucleotide therapeutics.

PMID- 16898415
TI  - The influences of a nitrogen atom position in dinucleoside 2-,3-,4
      pyridylphosphonates on fragmentation patterns in electrospray ionization
      multistage tandem mass spectra.
AB  - 2-,3-,4-Pyridylphosphonates and their phosphonothioate congeners were analyzed by
      electrospray ionization multistage tandem mass spectrometry (ESI-MS(n)). It was
      found that the fragmentation pathways of these compounds were not influenced to
      any detectable extent by the stereochemistry at the phosphorus centers but were
      sensitive to the position of a nitrogen atom in the pyridine ring of these
      compounds. Possible mechanisms for fragmentations of the investigated compounds
      are discussed in detail.

PMID- 16898416
TI  - Brief communication: stability and catalytic activity of novel circular DNAzymes.
AB  - DNAzymes represent a new generation of catalytic nucleic acids for specific RNA
      targeting in order to inhibit protein translation from the specifically cleaved
      mRNA. The 10-23 DNAzyme was found to hydrolyze RNA in a sequence-specific manner
      both in vitro and in vivo. Although single-stranded DNAzymes may represent the
      most effective nucleic acid drug to date, they are nevertheless sensitive to
      nuclease degradation and require modifications for in vivo application. However,
      previously used stabilization of DNAzymes by site-specific phosphorothioate (PT)
      modifications reduces the catalytic activity, and the PTO displays toxic side
      effects when applied in vivo. Thus, improving the stability of DNAzymes without
      reducing their catalytic activity is essential if the potential of these
      compounds should be realized in vivo. RESULTS: The Circozyme was tested targeting
      the mRNA of the most common genetic rearrangement in pediatric acute
      lymphoblastic leukemia TEL/AML1 (ETV6/RUNX1). The Circozyme exhibits a stability
      comparable to PTO-modified DNAzymes without reduction of catalytic activity and
      specificity and may represent a promising tool for DNAzyme in vivo applications.
      CONCLUSION: The inclusion of the catalytic site and the specific mRNA binding
      sequence of the DNAzyme into a circular loop-stem-loop structure (Circozyme) of
      approximately 70 bases presented here represents a new effective possibility of
      DNAzyme stabilization.

PMID- 16898418
TI  - Inhibition of hcv replication in HCV replicon by shRNAs.
AB  - We show that the vector-derived long dsRNA specifically inhibits the replication
      of HCV RNA in HCV replicon. We designed a long dsRNA targeted to the full-length
      HCV IRES/core elements (1-to 377-nt). Our results revealed that the replication
      of HCV RNA was reduced to near background levels in a sequence-specific manner by
      the long dsRNAs in the HCV replicon. We also designed four shRNAs against several
      regions (120- to 139-nt, 260- to 279-nt, 330- to 349-nt, and 340- to 359-nt) of
      the HCV IRES/Core elements. The two HCV IRES/core-specific shRNAs, 330- to 349-nt
      and 340- to 359-nt, containing the AUG initiation codon sequence showed stronger
      HCV inhibitory effects than the other two shRNAs, 120- to 139-nt and 260- to 279
      nt.

PMID- 16898417
TI  - Silencing of HIV-1 gene expression by siRNAs in transduced cells.
AB  - The RNA interference (RNAi) phenomenon is a recently observed process in which
      the introduction of a double-stranded RNA (dsRNA) into cells causes the specific
      degradation of an mRNA containing the same sequence. To study dsRNA-mediated gene
      interference targeted to the env gene (NL4-3: 7490-7508) in HIV-1 infected cells,
      we constructed tandem-type and hairpin-type siRNA expression vectors, which were
      under the control of two U6 promoters. We also constructed lentiviral-based siRNA
      expression vectors for further assessment of their antiviral activity in
      transduced cells. At both the transient plasmid and lentiviral-mediated RNA
      expression levels, the siRNA encoding the env fragment exhibited sequence
      specific suppression of target gene expression and strongly inhibited (> or =
      90%) HIV-1 infection in the cells, as compared to the antisense RNA expression
      vector. Targeting the HIV-1 env gene with siRNAs encoding the env gene fragment
      (7490-7508) might be an effective strategy for gene therapy applications in HIV
      1/AIDS treatment and management.

PMID- 16898419
TI  - The practical and pedagogical advantages of an ambigraphic nucleic acid notation.
AB  - The universally applied IUPAC notation for nucleic acids was adopted primarily to
      facilitate the mental association of G, A, T, C, and the related ambiguity
      characters with the bases they represent. However it is possible to create a
      notation that offers greater support for the basic manipulations and analyses to
      which genetic sequences frequently are subjected. By designing a nucleic acid
      notation around ambigrams, it is possible to simplify the frequently applied
      process of reverse complementation and aid the visualization of palindromes. The
      ambigraphic notation presented here also uses common orthographic features such
      as stems and loops to highlight guanine and cytosine rich regions, support the
      derivation of ambiguity characters, and aid educators in teaching the
      fundamentals of molecular genetics.

PMID- 16898420
TI  - Effect of microwave irradiation on phosphoramidite couplings on controlled pore
      glass.
AB  - The chain extension step in the synthesis of DNA oligomers on controlled pore
      glass was shown to be higher yielding when the reaction mixture is irradiated
      with microwaves. Both a commercial thymidine 3'-phosphoramidite building block
      and a 3'-phosphoramidite of protected 1'-aminomethylthymidine were coupled using
      dilute solutions that give only partial conversion. In either case, higher
      coupling yields were observed when microwaves were used. The results of our
      exploratory experiments suggest that microwave-assisted DNA syntheses might
      require fewer equivalents of phosphoramidites and/or shorter coupling times than
      those performed at room temperature.

PMID- 16898421
TI  - Characterization of the aldehyde reactive probe reaction with AP-sites in DNA:
      influence of AP-lyase on adduct stability.
AB  - Alkoxyamines react with the open-chain aldehyde form of AP-sites in DNA to
      produce open-chain aldehyde oximes. Here we characterize the effect of AP-site
      cleavage by yeast AP-endonuclease 1 (APN1) or T4 pyrimidine dimer DNA
      glycosylase/AP-lyase (T4 Pdg) on the efficiency and stability of the alkoxyamine
      aldehyde reactive probe (ARP) condensation reaction with AP-sites. The results
      indicate that (1) reaction of ARP with the open-chain aldehyde equilibrium form
      of the AP-site was less efficient than with the 3'-alpha,beta-unsaturated
      aldehyde produced by T4 Pdg; (2) the dRP moiety was least reactive with ARP; (3)
      both the AP-site and 3'-alpha,beta-unsaturated aldehyde were stable with regard
      to reaction with ARP over a 30-min incubation period at 37 degrees C; and (4) ARP
      adducted to the open-chain aldehyde form of the AP-site could be replaced by
      methoxyamine, but the 3'-alpha,beta-unsaturated aldehyde ARP oxime was stable
      against methoxyamine attack.

PMID- 16898422
TI  - Completing and updating health history forms.

PMID- 16898423
TI  - What is an "at-will" employer?

PMID- 16898424
TI  - All systems go!

PMID- 16898425
TI  - Health reimbursement arrangements--what are they?

PMID- 16898426
TI  - Michigan's dental Medicaid program: back and working better for you.

PMID- 16898427
TI  - Dry mouth: managing the symptoms and providing effective relief.

PMID- 16898428
TI  - Review of the use of polymers in saliva substitutes for symptomatic relief of
      xerostomia.
AB  - It is clear from the many clinical studies carried out on currently available
      saliva substitutes, that the main factors limiting the success of polymers in
      treating xerostomia is their short duration of action and/or their lack of
      acceptability by users. The most effective formulations for severe sufferers of
      xerostomia contain relatively viscous, thixotropic polymers, which mild to
      moderate sufferers in particular tend to dislike. Relief can also be extended by
      increasing concentrations of non-thixotropic polymers; however, this also has to
      be balanced by the decrease in palatability resulting from higher polymer levels.
      In addition, gels rather than solutions tend to result from higher polymer
      concentrations, which are only employed by the most severe sufferers of
      xerostomia, and in fact, have been suggested to offer little improvement in
      efficacy over oral sprays. It would be highly advantageous to improve the
      duration of relief without impacting negatively on the sensory profile of the
      product. This would provide a longer lasting effect that is acceptable to all
      sufferers of xerostomia. The essential role of polymers in saliva substitutes is
      to provide lubrication, hydration, and protection of the oral mucosa, providing
      symptomatic relief to sufferers of xerostomia. However, saliva substitutes should
      also be of neutral or near neutral pH, to prevent demineralization of the oral
      hard tissues. These products should always be used in conjunction with a thorough
      oral health regimen, but may also contain appropriate levels of electrolytes for
      remineralization of enamel and dentine.

PMID- 16898429
TI  - Evaluation of a combined polymer system for use in relieving the symptoms of
      xerostomia.
AB  - OBJECTIVE: The aim of this series of studies on rheological, sensory, and
      mucoadhesive properties was to evaluate the potential of using a combined polymer
      system to more closely represent the adaptive nature of saliva, while providing
      long lasting relief from the symptoms of xerostomia. METHODOLOGY: The rheological
      investigations were conducted on 1% polymer solutions 24 hours after preparation,
      during which time they were stored in sealed glass containers at room
      temperature. The rheometer was controlled via peltier to 35 degrees C +/- 0.1
      degrees C, and a shear rate range of 0.1 to 300 s(-1) was applied; thirty
      measurements were taken during each run. Eight panelists were recruited from the
      in-house sensory panel at GlaxoSmithKline (GSK) Weybridge to take part in the
      sensory evaluation. A brief training session was conducted at the start of the
      study in order to standardize the panelists' responses to the sensory term
      "tacky." For each test, panelists were given 10 ml of the respective polymer
      solution and instructed to swirl this solution around their mouths for 20 seconds
      before expectorating. The panelists were then asked to evaluate the solution in
      terms of "tack," measured by tapping the tongue on the roof of the mouth. A new
      formulation, based upon the rheology and sensory testing, was evaluated versus
      other commercially available sprays for the relief of xerostomia. The new
      formulation, named OASIS, contains a combination of Xanthan gum, carboxymethyl
      cellulose and a polyvinyl pyrollidone backboned polymer. To evaluate mucoadhesion
      of this final product, a 16 mm diameter cylindrical aluminium probe was selected.
      The probe and the base platform were both coated with a thin layer of artificial
      polyurethane membrane to more closely mimic the oral mucosal surface. The probe
      was set to travel downward at 2.0 mm/sec until it made contact with the base
      platform with a force of 1000 g. The two surfaces were then left in contact for
      30 seconds before the probe receded from the base platform at 0.5 mm/sec to a
      distance of 10 mm. A plot of force versus distance was obtained, and the area
      under the curve (defined as the Work of Adhesion, energy required to separate the
      two surfaces) was used as a measure of the mucoadhesion of the materials.
      RESULTS: For rheology, the Xanthan gum solution showed high initial viscosity of
      32 Pa.s at 0.1 s(-1) with rapid shear thinning to 4.0 Pa.s. By 1.2 s(-1) the
      viscosity continued to drop with increasing shear rate to 0.05 Pa.s at 300 s(-1).
      For the sensory assessment, the CMC single solution was perceived to be
      significantly (p = 0.04) more tacky than the CMC + PVP solution. The Xanthan +
      PVP solution was perceived to be less tacky (slightly/moderately tacky) than the
      Xanthan solution (moderately tacky). The Xanthan + CMC + PVP solution was
      perceived to be less tacky (slightly tacky) than the Xanthan + CMC solution
      (moderately tacky). Overall, there was a significant difference in favor of the
      inclusion of PVP across the products (p = 0.038), which was also shown to be a
      consistent effect across the different polymer solutions. CONCLUSION: The sensory
      solution work indicates that the addition of a PVP backbone polymer within an
      anionic polymer solution (OASIS) enables higher concentrations of mucoadhesive
      polymer to be included within a dry mouth formulation, while at the same time
      giving improved mouth-feel due to reduced tack.

PMID- 16898430
TI  - Subjective assessment of a new moisturizing mouthwash for the symptomatic
      management of dry mouth.
AB  - OBJECTIVE: A randomized clinical trial and consumer usage test were conducted to
      evaluate the acceptability and benefits of OASIS Moisturizing Mouthwash in
      subjects experiencing symptoms of dry mouth. METHODOLOGY: Study 1: A randomized,
      double blind, two-period crossover clinical trial was conducted in 49 subjects to
      evaluate OASIS Moisturizing Mouthwash and an experimental mouthwash formulation.
      Following a three-day acclimatization phase, subjects used both products at home
      for three days. Each treatment phase was separated by a three-day washout period.
      Study 2: Subjects participated in a one- to two-week home usage consumer test
      using OASIS Moisturizing Mouthwash, after which they completed a 52-question
      online survey exploring sensory benefits and resultant quality of life attributes
      of the product. RESULTS: Study 1: A total of 46 adults with a mean age of 64
      years completed the study. On average, subjects used the test products three
      times per day. OASIS Moisturizing Mouthwash was found to be beneficial in
      managing dry mouth, and was well-liked by the study population, as evidenced by a
      statistically significant improvement over subjects' normal remedies for managing
      dry mouth for strength of flavor, taste, freshening breath, immediate and long
      lasting lubrication, and moisturization. Both products were well-tolerated. Study
      2: Three-hundred and twenty-three subjects completed a one- to two-week consumer
      home usage test followed by an online questionnaire. On a five-point scale, over
      80% of respondents perceived the OASIS Moisturizing Mouthwash as "excellent" or
      "very good" on sensory attributes such as taste and texture, and 70-80% gave the
      product an "excellent" or "very good" rating on benefit attributes. CONCLUSION:
      These studies showed that OASIS Moisturizing Mouthwash was beneficial in managing
      dry mouth, and was well-liked by the study population.

PMID- 16898432
TI  - Point/Counterpoint. The proposed MOC requirements for physicists are reasonable.

PMID- 16898431
TI  - Subjective assessment of a new moisturizing mouth spray for the symptomatic
      relief of dry mouth.
AB  - OBJECTIVE: A randomized clinical trial (Study 1) and consumer usage test (Study
      2) were conducted to evaluate the acceptability and efficacy of OASIS Mouth
      Moisturizing Spray in subjects experiencing dry mouth. METHODOLOGY: Study 1: A
      randomized, single-blind, four-arm crossover clinical trial was conducted in 24
      subjects, ranging from 50-84 years of age, to evaluate OASIS Mouth Moisturizing
      Spray and two experimental mouth spray formulations, and compare their
      performance to a reference (marketed) mouth spray, SALIVEZE. Following a three
      day acclimatization phase, subjects used all four products at home for three
      days. Each treatment phase was separated by a three-day washout period. Study 2:
      One-hundred twenty subjects participated in a three-week home usage consumer test
      using OASIS Mouth Moisturizing Spray, after which they completed a 52-question
      online survey exploring sensory, efficacy, and resultant quality of life
      attributes of the product. RESULTS: Study 1: On average, subjects used the four
      test products 2-3 times per day. OASIS Mouth Moisturizing Spray was found to be
      effective in relieving dry mouth in the study population, as evidenced by a
      statistically significant feeling of coating the mouth (p < 0.05), and
      statistically significantly longer dry mouth relief (p < 0.005) than the
      commercial control. The OASIS Mouth Moisturizing Spray was statistically
      significantly (p < 0.05) better and preferred over the other product tested. All
      the products used in the study were well-tolerated. Study 2: On a five-point
      scale, 73% of respondents perceived the OASIS Mouth Moisturizing Spray as "very
      good" or "excellent," and more than 60% gave the product an "excellent" or "very
      good" rating on sensory, efficacy, and quality of life attributes. CONCLUSION:
      These studies show that OASIS Mouth Moisturizing Spray helped provide dry mouth
      relief and was well liked by the study population.

PMID- 16898434
TI  - Computer-aided diagnosis of pulmonary nodules on CT scans: segmentation and
      classification using 3D active contours.
AB  - We are developing a computer-aided diagnosis (CAD) system to classify malignant
      and benign lung nodules found on CT scans. A fully automated system was designed
      to segment the nodule from its surrounding structured background in a local
      volume of interest (VOI) and to extract image features for classification. Image
      segmentation was performed with a three-dimensional (3D) active contour (AC)
      method. A data set of 96 lung nodules (44 malignant, 52 benign) from 58 patients
      was used in this study. The 3D AC model is based on two-dimensional AC with the
      addition of three new energy components to take advantage of 3D information: (1)
      3D gradient, which guides the active contour to seek the object surface, (2) 3D
      curvature, which imposes a smoothness constraint in the z direction, and (3) mask
      energy, which penalizes contours that grow beyond the pleura or thoracic wall.
      The search for the best energy weights in the 3D AC model was guided by a simplex
      optimization method. Morphological and gray-level features were extracted from
      the segmented nodule. The rubber band straightening transform (RBST) was applied
      to the shell of voxels surrounding the nodule. Texture features based on run
      length statistics were extracted from the RBST image. A linear discriminant
      analysis classifier with stepwise feature selection was designed using a second
      simplex optimization to select the most effective features. Leave-one-case-out
      resampling was used to train and test the CAD system. The system achieved a test
      area under the receiver operating characteristic curve (A(z)) of 0.83 +/- 0.04.
      Our preliminary results indicate that use of the 3D AC model and the 3D texture
      features surrounding the nodule is a promising approach to the segmentation and
      classification of lung nodules with CAD. The segmentation performance of the 3D
      AC model trained with our data set was evaluated with 23 nodules available in the
      Lung Image Database Consortium (LIDC). The lung nodule volumes segmented by the
      3D AC model for best classification were generally larger than those outlined by
      the LIDC radiologists using visual judgment of nodule boundaries.

PMID- 16898435
TI  - X-ray imaging in advanced studies of ophthalmic diseases.
AB  - Microscopic characterization of pathological tissues has one major intrinsic
      limitation, the small sampling areas with respect to the extension of the
      tissues. Mapping possible changes on vast tissues and correlating them with large
      ensembles of clinical cases is not a feasible procedure for studying most
      diseases, as for instance vision loss related diseases and, in particular, the
      cataract. Although intraocular lens implants are successful treatments, cataract
      still is a leading public-health issue that grows in importance as the population
      increases and life expectancy is extended worldwide. In this work we have
      exploited the radiation-tissue interaction properties of hard x-rays--very low
      absorption and scattering--to map distinct lesions on entire eye lenses. At the
      used synchrotron x-ray photon energy of 20 keV (wavelength lambda=0.062 nm),
      scattering and refraction are angular resolved effects. It allows the employed x
      ray image technique to efficiently characterize two types of lesions in eye
      lenses under cataractogenesis: distributions of tiny scattering centers and
      extended areas of fiber cell compaction. The data collection procedure is
      relatively fast; allowing dozens of samples to be totally imaged (scattering,
      refraction, and mass absorption images) in a single day of synchrotron beam time.
      More than 60 cases of canine cataract, not correlated to specific causes, were
      investigated in this first application of x-rays to image entire lenses. Cortical
      opacity cases, or partial opacity, could be related to the presence of
      calcificated tissues at the cortical areas, clearly visible in the images, whose
      elemental contents were verified by micro x-ray fluorescence as very rich in
      calcium. Calcificated tissues were also observed at nuclear areas in some cases
      of hypermature cataract. Total opacity cases without distinguishable amount of
      scattering centers consist in 70% of the analyzed cases, where remarkable fissure
      marks owing to extended areas of fiber cell compaction are diagnosed.

PMID- 16898436
TI  - Patient position verification using small IMRT fields.
AB  - A commonly used approach to quantify and minimize patient setup errors is by
      using electronic portal imaging devices (EPIDs). The position of the tumor can be
      verified indirectly by matching the bony anatomy to a reference image containing
      the same structures. In this paper we present two off-line methods for detecting
      the position of the bony anatomy automatically, even if every single portal image
      of each segment of an IMRT treatment beam contains insufficient matching
      information. Extra position verification fields will no longer be necessary,
      which reduces the total dose to the patient. The first method, the stack matching
      method (SMM), stacks the portal image of each segment of a beam to a three
      dimensional (3D) volume, and this volume is subsequently used during the matching
      phase. The second method [the averaged projection matching method (APMM)], is a
      simplification of the first one, since the initially created volume is reduced
      again to a 2D artificial image, which speeds up the matching procedure
      considerably, without a significant loss of accuracy. Matching is based on
      normalized mutual information. We demonstrate our methods by comparing them to
      existing matching routines, such as matching based on the largest segment. Both
      phantom and patient experiments show that our methods are comparable with the
      results obtained from standard position verification methods. The matches are
      verified by means of visual inspection. Furthermore, we show that when a distinct
      area of 40-60 cm2 of the EPID is exposed during one treatment beam, both SMM and
      APMM are able to deliver a good matching result.

PMID- 16898437
TI  - Integrating respiratory gating into a megavoltage cone-beam CT system.
AB  - We have previously described a low-dose megavoltage cone beam computed tomography
      (MV CBCT) system capable of producing projection image using one beam pulse. In
      this study, we report on its integration with respiratory gating for gated
      radiotherapy. The respiratory gating system tracks a reflective marker on the
      patient's abdomen midway between the xiphoid and umbilicus, and disables
      radiation delivery when the marker position is outside predefined thresholds. We
      investigate two strategies for acquiring gated scans. In the continuous rotation
      gated acquisition, the linear accelerator (LINAC) is set to the fixed x-ray mode
      and the gantry makes a 5 min, 360 degree continuous rotation, during which the
      gating system turns the radiation beam on and off, resulting in projection images
      with an uneven distribution of projection angles (e.g., in 70 arcs each covering
      2 degrees). In the gated rotation-continuous acquisition, the LINAC is set to the
      dynamic arc mode, which suspends the gantry rotation when the gating system
      inhibits the beam, leading to a slightly longer (6-7 min) scan time, but yielding
      projection images with more evenly distributed projection angles (e.g.,
      approximately 0.8 degrees between two consecutive projection angles). We have
      tested both data acquisition schemes on stationary (a contrast detail and a
      thoracic) phantoms and protocol lung patients. For stationary phantoms, a
      separate motion phantom not visible in the images is used to trigger the RPM
      system. Frame rate is adjusted so that approximately 450 images (13 MU) are
      acquired for each scan and three-dimensional tomographic images reconstructed
      using a Feldkamp filtered backprojection algorithm. The gated rotation-continuous
      acquisition yield reconstructions free of breathing artifacts. The tumor in
      parenchymal lung and normal tissues are easily discernible and the boundary
      between the diaphragm and the lung sharply defined. Contrast-to-noise ratio (CNR)
      is not degraded relative to nongated scans of stationary phantoms. The continuous
      rotation-gated acquisition scan also yields tomographic images with discernible
      anatomic features; however, streak artifacts are observed and CNR is reduced by
      approximately a factor of 4. In conclusion, we have successfully developed a
      gated MV CBCT system to verify the patient positioning for gated radiotherapy.

PMID- 16898438
TI  - On measuring depth-dose distribution of range-modulated proton therapy fields.
AB  - Depth-dose profile measurements are frequently performed for the characterization
      of spread-out Bragg peak treatment fields in proton therapy. The measured
      distribution often contains a significant amount of noise with a persistent
      pattern. As a result, substantial smoothing has to be applied which can alter a
      measurement. We explored the origin of the observed noise by closely examining
      the sampling process in the scanning algorithm. We will show that the time
      characteristics of the signal in the range-modulated proton therapy beams differ
      significantly from those in the photon beams, and as a result the measurement
      error is very sensitive to the sampling duration. The observed noise results
      mainly from inappropriate choices for this value, rather than from the dose
      distribution itself. Increasing the value arbitrarily may actually increase the
      noise magnitude. We will demonstrate that with an optimal value for the sampling
      duration and its accurate control, the noise magnitude can be reduced
      significantly, without increasing the measurement time.

PMID- 16898439
TI  - Application of the electron pencil beam redefinition algorithm to electron arc
      therapy.
AB  - This project investigated the potential of summing fixed-beam dose distributions
      calculated using the pencil-beam redefinition algorithm (PBRA) at small angular
      steps (1 degree) to model an electron arc therapy beam. The PRBA, previously
      modified to model skin collimation, was modified further by incorporating two
      correction factors. One correction factor that is energy, SSD (source-to-surface
      distance), and field-width dependent constrained the calculated dose output to be
      the same as the measured dose output for fixed-beam geometries within the range
      of field widths and SSDs encountered in arc therapy. Another correction factor
      (single field-width correction factor for each energy) compensated for large
      angle scattering not being modeled, allowing a more accurate calculation of dose
      output at mid arc. The PBRA was commissioned to accurately calculate dose in a
      water phantom for fixed-beam geometries typical of electron arc therapy.
      Calculated central-axis depth doses agreed with measured doses to within 2% in
      the low-dose gradient regions and within 1-mm in the high-dose gradient regions.
      Off-axis doses agreed to within 2 mm in the high-dose gradient regions and within
      3% in the low-dose gradient regions. Arced-beam calculations of dose output and
      depth dose at mid arc were evaluated by comparing to data measured using two
      cylindrical water phantoms with radii of 12 and 15 cm at 10 and 15 MeV. Dose
      output was measured for all combinations of phantom radii of curvature,
      collimator widths (4, 5, and 6 cm), and arc angles (0 degrees, 20 degrees, 40
      degrees, 60 degrees, 80 degrees, and 90 degrees) for both beam energies. Results
      showed the calculated mid-arc dose output to agree within 2% of measurement for
      all combinations. For a 90 degree arc angle and 5 x 20 cm2 field size, the
      calculated mid-arc depth dose in the low-dose gradient region agreed to within 2%
      of measurement for all depths at 10 MeV and for depths greater than depth of dose
      maximum R100 at 15 MeV. For depths in the buildup region at 15 MeV the
      calculations overestimated the measured dose by as much as 3.4%. Mid-arc depth
      dose in the high-dose gradient region agreed to within 2.2 mm of measured dose.
      Calculated two-dimensional relative dose distributions in the plane of rotation
      were compared to dose measurements using film in a cylindrical polystyrene
      phantom for a 90 degree arc angle and field widths of 4, 5, and 6 cm at 10 and 15
      MeV. Results showed that off-axis dose at the ends of arc (without skin
      collimation) agreed to within 2% in the low-dose gradient region and to within
      1.2 mm in the high-dose gradient region. This work showed that the accuracy of
      the PBRA arced-beam dose model met the criteria specified by Van Dyk et al. [Int.
      J. Radiat. Oncol. Biol. Phys. 26, 261-273 (1993)] with the exception of the
      buildup region of the 15 MeV beam. Based on the present results, results of a
      previous study showing acceptable accuracy in the presence of skin collimation,
      and results of a previous study showing acceptable accuracy in the presence of
      internal heterogeneities, it is concluded that the PBRA arced-beam dose model
      should be adequate for planning electron arc therapy.

PMID- 16898441
TI  - Data required for testicular dose calculation during radiotherapy of seminoma.
AB  - The purpose of this study was to provide the required data for the direct
      calculation of testicular dose resulting from radiotherapy in patients with
      seminoma. Paraortic (PA) treatment fields and dog-leg (DL) portals including
      paraortic and ipsilateral pelvic nodes were simulated on a male anthropomorphic
      phantom equipped with an artificial testicle. Anterior and posterior irradiations
      were performed for five different PA and DL field dimensions. Dose measurements
      were carried out using a calibrated ionization chamber. The dependence of
      testicular dose upon the distance separating the testicle from the treatment
      volume and upon the tissue thickness at the entrance point of the beam was
      investigated. A clamshell lead shield was used to reduce testicular dose. The
      scattered dose to testicle was measured in nine patients using thermoluminescent
      dosimeters. Phantom and patient exposures were generated with a 6 MV x-ray beam.
      Linear and nonlinear regression analysis was employed to obtain formulas
      describing the relation between the radiation dose to an unshielded and/or
      shielded testicle with the field size and the distance from the inferior field
      edge. Correction factors showing the variation of testicular dose with the
      patient thickness along beam axis were found. Bland-Altman statistical analysis
      showed that testicular dose obtained by the proposed calculation method may
      differ from the measured dose value by less than 25%. The current study presents
      a method providing reasonable estimations of testicular dose for individual
      patients undergoing PA or DL radiotherapy.

PMID- 16898440
TI  - Dosimetry of a thyroid uptake detected in seed migration survey following a
      patient's iodine-125 prostate implant and in vitro measurements of intentional
      seed leakages.
AB  - As a quality control procedure, a post-implant seed migration survey has been
      accomplished on 340 prostate cancer patients since November 2001. Pulmonary seed
      embolization and intracardiac seed embolization have been detected. A case of
      thyroid uptake due to leaking iodine-125 (I-125) sources was also seized. In
      order to determine the dose to the thyroid, a dosimetry method was developed to
      link in vivo measurements and the cumulated dose to the thyroid. The calculated
      source leakage half-life in the case was approximately 15 days based on the
      measurements and the estimated cumulated dose to thyroid was 204 cGy. It is
      concluded that one seed was leaking. In order to verify the in vivo measurements,
      intentional in vitro seed leakage tests were performed. A seed was cut open and
      placed in a sealed glass container filled with a given volume of saline. The I
      125 concentration in the saline was subsequently measured over a period of six
      months. Consistent in vivo and in vitro results were obtained. Recent incidents
      of seed leaks reported from other centers have drawn practitioners' attention to
      this problem. In order to make the measurements more useful, the seed leakage
      tests were expanded to include I-125 seeds from six other vendors. The results
      show that the leakage half-lives of those seeds varied from nine days to a half
      year. Two seed models demonstrated least leakage. Since the measurements lasted
      for six months, the escape of iodine resulted from oxidation of iodide in the
      saline was a concern for the measurement accuracy. As a reference, another set of
      leakage tests were performed by adding sodium thiosulfate salt (Na2S2O3 x 5 H2O)
      to the saline. Sodium thiosulfate is a reducing agent that prevents the
      conversion of iodide to iodate so as to minimize I-125 evaporation. As a result,
      significantly shortened leakage half-lives were observed in this group. Seed
      agitation was also performed and no significant deviations of the leakage rates
      were observed. Considering the body fluid is more complex than saline, the in
      vivo leakage half-life, in case a source leak is encountered, may vary
      significantly from what is presented in this paper due to chemical reactions. In
      vivo measurements thus may produce a more accurate estimation of leakage half
      life and thyroid uptake dose.

PMID- 16898442
TI  - The curvature of sensitometric curves for Kodak XV-2 film irradiated with photon
      and electron beams.
AB  - Sensitometric curves of Kodak XV-2 film, obtained in a time period of ten years
      with various types of equipment, have been analyzed both for photon and electron
      beams. The sensitometric slope in the dataset varies more than a factor of 2,
      which is attributed mainly to variations in developer conditions. In the
      literature, the single hit equation has been proposed as a model for the
      sensitometric curve, as with the parameters of the sensitivity and maximum
      optical density. In this work, the single hit equation has been translated into a
      polynomial like function as with the parameters of the sensitometric slope and
      curvature. The model has been applied to fit the sensitometric data. If the
      dataset is fitted for each single sensitometric curve separately, a large
      variation is observed for both fit parameters. When sensitometric curves are
      fitted simultaneously it appears that all curves can be fitted adequately with a
      sensitometric curvature that is related to the sensitometric slope. When fitting
      each curve separately, apparently measurement uncertainty hides this relation.
      This relation appears to be dependent only on the type of densitometer used. No
      significant differences between beam energies or beam modalities are observed.
      Using the intrinsic relation between slope and curvature in fitting sensitometric
      data, e.g., for pretreatment verification of intensity-modulated radiotherapy,
      will increase the accuracy of the sensitometric curve. A calibration at a single
      dose point, together with a predetermined densitometer-dependent parameter ODmax
      will be adequate to find the actual relation between optical density and dose.

PMID- 16898443
TI  - Automated localization of implanted seeds in 3D TRUS images used for prostate
      brachytherapy.
AB  - An algorithm has been developed in this paper to localize implanted radioactive
      seeds in 3D ultrasound images for a dynamic intraoperative brachytherapy
      procedure. Segmentation of the seeds is difficult, due to their small size in
      relatively low quality of transrectal ultrasound (TRUS) images. In this paper,
      intraoperative seed segmentation in 3D TRUS images is achieved by performing a
      subtraction of the image before the needle has been inserted, and the image after
      the seeds have been implanted. The seeds are searched in a "local" space
      determined by the needle position and orientation information, which are obtained
      from a needle segmentation algorithm. To test this approach, 3D TRUS images of
      the agar and chicken tissue phantoms were obtained. Within these phantoms, dummy
      seeds were implanted. The seed locations determined by the seed segmentation
      algorithm were compared with those obtained from a volumetric cone-beam flat
      panel micro-CT scanner and human observers. Evaluation of the algorithm showed
      that the rms error in determining the seed locations using the seed segmentation
      algorithm was 0.98 mm in agar phantoms and 1.02 mm in chicken phantoms.

PMID- 16898444
TI  - Dose uncertainty due to aperture effects in dynamic fields.
AB  - Dosimetry of intensity modulated radiation therapy requires accurate modeling of
      the beamlets that comprise each treatment segment. Planning systems such as
      Varian Eclipse and Philips Pinnacle recommend measuring dose distributions and
      output factors for fields as small as possible, generally down to at least 2 x 2
      cm2. Conventionally, we perform these measurements for regular fields, defined by
      the secondary collimators. In practice, it is the multileaf collimation system
      (MLC) that defines the intensity map and provides dynamic dose modulation in
      either a moving window or segmented step-and-shoot mode. For this review we have
      only considered the latter delivery mode. Using this method, we have studied
      aperture motion effects on the dynamic collimator scatter (S(c)), total scatter
      (S(c,p)), and phantom scatter (S(p)) factors for various combinations of
      collimator settings (4 x 4-14 x 40 cm2) and dynamically stepped leaf gaps (0.1 to
      1.0 cm) in comparison with those for static field factors. For two different
      Varian linear accelerators, we found similar results in a systematic dependence
      of collimator scatter on gap width and collimator setting. As the gap increases
      from 0.1 to 1.0 cm the dynamic collimator scatter factors converge from a maximum
      difference of about 30% toward the static field values. At the same time, there
      is no measurable difference between dynamic field phantom scatter factors and
      those conventionally obtained for static fields. Second, we evaluated the two
      planning systems as to how well they account for collimator scatter by attempting
      to mimic the dynamic apertures used above by planning and measuring dose
      distributions to several small, cylindrical targets for a similar range of fixed
      collimator settings. We found that the ratio of measured-to-planned doses as a
      function of target size were similar to the measured, dynamic S(c) data for the
      Varian Eclipse planning system, indicating underestimation of dose for targets
      smaller than 1 cm diameter, but were close to unity for the Philips Pinnacle
      system, suggestive of the underlying differences in the dose calculation
      algorithms. We discuss the measurements and results and potential impact on the
      dosimetry of small clinical targets.

PMID- 16898445
TI  - A Monte Carlo based three-dimensional dose reconstruction method derived from
      portal dose images.
AB  - The verification of intensity-modulated radiation therapy (IMRT) is necessary for
      adequate quality control of the treatment. Pretreatment verification may trace
      the possible differences between the planned dose and the actual dose delivered
      to the patient. To estimate the impact of differences between planned and
      delivered photon beams, a three-dimensional (3-D) dose verification method has
      been developed that reconstructs the dose inside a phantom. The pretreatment
      procedure is based on portal dose images measured with an electronic portal
      imaging device (EPID) of the separate beams, without the phantom in the beam and
      a 3-D dose calculation engine based on the Monte Carlo calculation. Measured gray
      scale portal images are converted into portal dose images. From these images the
      lateral scattered dose in the EPID is subtracted and the image is converted into
      energy fluence. Subsequently, a phase-space distribution is sampled from the
      energy fluence and a 3-D dose calculation in a phantom is started based on a
      Monte Carlo dose engine. The reconstruction model is compared to film and
      ionization chamber measurements for various field sizes. The reconstruction
      algorithm is also tested for an IMRT plan using 10 MV photons delivered to a
      phantom and measured using films at several depths in the phantom. Depth dose
      curves for both 6 and 10 MV photons are reconstructed with a maximum error
      generally smaller than 1% at depths larger than the buildup region, and smaller
      than 2% for the off-axis profiles, excluding the penumbra region. The absolute
      dose values are reconstructed to within 1.5% for square field sizes ranging from
      5 to 20 cm width. For the IMRT plan, the dose was reconstructed and compared to
      the dose distribution with film using the gamma evaluation, with a 3% and 3 mm
      criterion. 99% of the pixels inside the irradiated field had a gamma value
      smaller than one. The absolute dose at the isocenter agreed to within 1% with the
      dose measured with an ionization chamber. It can be concluded that our new dose
      reconstruction algorithm is able to reconstruct the 3-D dose distribution in
      phantoms with a high accuracy. This result is obtained by combining portal dose
      images measured prior to treatment with an accurate dose calculation engine.

PMID- 16898446
TI  - Multithreaded cardiac CT.
AB  - Phase-correlated CT, as it is used for cardiac imaging, is the most popular and
      the most important but also the most demanding special CT application in the
      clinical routine, today. Basically, it fulfills the four-dimensional imaging task
      of depicting a quasiperiodically moving object at any desired motion phase with
      significantly reduced motion artifacts. Although image quality with phase
      correlated reconstruction is far better than with standard reconstruction, there
      are motion artifacts remaining and improvements of temporal resolution are
      required. As a well-known alternative to simply decreasing rotation time, we
      consider a spiral cone-beam CT scanner that has G x-ray guns and detectors
      mounted. We call this a multisource or a multithreaded CT scanner. Aiming for
      improved temporal resolution the relative temporal resolution tau, which measures
      the fraction of a motion period that enters the image, is studied as a function
      of the motion rate (heart rate) and the degree of scan overlap (pitch value) for
      various configurations. The parameters to optimize are the number of threads G
      and the interthread parameters delta alpha and delta z, which are the angular and
      the longitudinal separation between adjacent threads, respectively. To
      demonstrate the improvements approximate image reconstruction of multithreaded
      raw data is performed by using a generalization of the extended parallel back
      projection cone-beam reconstruction algorithm [Med. Phys. 31(6), 1623-1641
      (2004)] to the case of multithreaded CT. Reconstructions of a simulated cardiac
      motion phantom and of simulated semi-antropomorphic phantoms are presented for
      two and three threads and compared to the single-threaded case to demonstrate the
      potential of multithreaded cardiac CT. Patient data were acquired using a
      clinical double-threaded CT scanner to validate the theoretical results. The
      optimum angle delta alpha between the tubes is 90 degrees for a double-threaded
      system, and for triple-threaded scanners it is 60 degrees or 120 degrees. In all
      cases, delta z = 0 results as an optimum, which means that the threads should be
      mounted in the same transversal plane. However, the dependency of the temporal
      resolution on delta z is very weak and a longitudinal separation delta z not = 0
      would not deteriorate image quality. The mean temporal resolution achievable with
      an optimized multithreaded CT scanner is a factor of G better than the mean
      temporal resolution obtained with a single-threaded scanner. The standard
      reconstructions showed decreased cone-beam artifacts with multithreaded CT
      compared to the single-threaded case. Our phase-correlated reconstructions
      demonstrate that temporal resolution is significantly improved with multithreaded
      CT. The clinical patient data confirm our results.

PMID- 16898447
TI  - Comparison of ghosting effects for three commercial a-Si EPIDs.
AB  - Many studies have reported dosimetric characteristics of amorphous silicon
      electronic portal imaging devices (EPIDs). Some studies ascribed a non-linear
      signal to gain ghosting and image lag. Other reports, however, state the effect
      is negligible. This study compares the signal-to-monitor unit (MU) ratio for
      three different brands of EPID systems. The signal was measured for a wide range
      of monitor units (5-1000), dose-rates, and beam energies. All EPIDs exhibited a
      relative under-response for beams of few MUs; giving 4 to 10% lower signal-to-MU
      ratios relative to that of 1000 MUs. This under-response is consistent with
      ghosting effects due to charge trapping.

PMID- 16898448
TI  - Marker-controlled watershed for lymphoma segmentation in sequential CT images.
AB  - Segmentation of lymphoma containing lymph nodes is a difficult task because of
      multiple variables associated with the tumor's location, intensity distribution,
      and contrast to its surrounding tissues. In this paper, we present a reliable and
      practical marker-controlled watershed algorithm for semi-automated segmentation
      of lymphoma in sequential CT images. Robust determination of internal and
      external markers is the key to successful use of the marker-controlled watershed
      transform in the segmentation of lymphoma and is the focus of this work. The
      external marker in our algorithm is the circle enclosing the lymphoma in a single
      slice. The internal marker, however, is determined automatically by combining
      techniques including Canny edge detection, thresholding, morphological operation,
      and distance map estimation. To obtain tumor volume, the segmented lymphoma in
      the current slice needs to be propagated to the adjacent slice to help determine
      the external and internal markers for delineation of the lymphoma in that slice.
      The algorithm was applied to 29 lymphomas (size range, 9-53 mm in diameter; mean,
      23 mm) in nine patients. A blinded radiologist manually delineated all lymphomas
      on all slices. The manual result served as the "gold standard" for comparison.
      Several quantitative methods were applied to objectively evaluate the performance
      of the segmentation algorithm. The algorithm received a mean overlap,
      overestimation, and underestimation ratios of 83.2%, 13.5%, and 5.5%,
      respectively. The mean average boundary distance and Hausdorff boundary distance
      were 0.7 and 3.7 mm. Preliminary results have shown the potential of this
      computer algorithm to allow reliable segmentation and quantification of lymphomas
      on sequential CT images.

PMID- 16898449
TI  - Voting strategy for artifact reduction in digital breast tomosynthesis.
AB  - Artifacts are observed in digital breast tomosynthesis (DBT) reconstructions due
      to the small number of projections and the narrow angular range that are
      typically employed in tomosynthesis imaging. In this work, we investigate the
      reconstruction artifacts that are caused by high-attenuation features in breast
      and develop several artifact reduction methods based on a "voting strategy." The
      voting strategy identifies the projection(s) that would introduce artifacts to a
      voxel and rejects the projection(s) when reconstructing the voxel. Four
      approaches to the voting strategy were compared, including projection
      segmentation, maximum contribution deduction, one-step classification, and
      iterative classification. The projection segmentation method, based on
      segmentation of high-attenuation features from the projections, effectively
      reduces artifacts caused by metal and large calcifications that can be reliably
      detected and segmented from projections. The other three methods are based on the
      observation that contributions from artifact-inducing projections have higher
      value than those from normal projections. These methods attempt to identify the
      projection(s) that would cause artifacts by comparing contributions from
      different projections. Among the three methods, the iterative classification
      method provides the best artifact reduction; however, it can generate many false
      positive classifications that degrade the image quality. The maximum contribution
      deduction method and one-step classification method both reduce artifacts well
      from small calcifications, although the performance of artifact reduction is
      slightly better with the one-step classification. The combination of one-step
      classification and projection segmentation removes artifacts from both large and
      small calcifications.

PMID- 16898450
TI  - The effect of z overscanning on radiation burden of pediatric patients undergoing
      head CT with multidetector scanners: a Monte Carlo study.
AB  - The purpose of this study was to investigate the effect of z overscanning on eye
      lens dose and effective dose received by pediatric patients undergoing head CT
      examinations. A pediatric patient study was carried out to obtain the exposure
      parameters and data regarding the eye lens position with respect to imaged volume
      boundaries. This information was used to simulate CT exposures by Monte Carlo
      code. The Monte Carlo N-Particle (MCNP, version 4C2) radiation transport code and
      five mathematical anthropomorphic phantoms representing newborn, 1-, 5-, 10-, and
      15-year-old patient, were employed in the current study. To estimate effective
      dose, the weighted computed tomography dose index was calculated by cylindrical
      polymethyl-methacrylate phantoms of 9.7, 13.1, 15.4, 16.1, and 16.9 cm in
      diameter representing the pediatric head of newborn, 1-, 5-, 10-, and 15-year-old
      individuals, respectively. The validity of the Monte Carlo calculated approach
      was verified by comparison with dose data obtained using physical pediatric
      anthropomorphic phantoms and thermoluminescence dosimetry. For all patients
      studied, the eye lenses were located in the region -1 to 3 cm from the first
      slice of the imaged volume. Doses from axial scans were always lower than those
      from corresponding helical examinations. The percentage differences in normalized
      eye lens absorbed dose between contiguous axial and helical examinations with
      pitch=1 were found to be up to 10.9%, when the eye lenses were located inside the
      region to be imaged. When the eye lenses were positioned 0-3 cm far from the
      first slice of region to be imaged, the normalized dose to the lens from
      contiguous axial examinations was up to 11 times lower than the corresponding
      values from helical mode with pitch=1. The effective dose from axial examinations
      was up to 24% lower than corresponding values from helical examinations with
      pitch=1. In conclusion, it is more dose efficient to use axial mode acquisition
      rather than helical scan for pediatric head examinations, if there are no
      overriding clinical considerations.

PMID- 16898451
TI  - Neutron scattered dose equivalent to a fetus from proton radiotherapy of the
      mother.
AB  - Scattered neutron dose equivalent to a representative point for a fetus is
      evaluated in an anthropomorphic phantom of the mother undergoing proton
      radiotherapy. The effect on scattered neutron dose equivalent to the fetus of
      changing the incident proton beam energy, aperture size, beam location, and air
      gap between the beam delivery snout and skin was studied for both a small field
      snout and a large field snout. Measurements of the fetus scattered neutron dose
      equivalent were made by placing a neutron bubble detector 10 cm below the
      umbilicus of an anthropomorphic Rando phantom enhanced by a wax bolus to simulate
      a second trimester pregnancy. The neutron dose equivalent in milliSieverts (mSv)
      per proton treatment Gray increased with incident proton energy and decreased
      with aperture size, distance of the fetus representative point from the field
      edge, and increasing air gap. Neutron dose equivalent to the fetus varied from
      0.025 to 0.450 mSv per proton Gray for the small field snout and from 0.097 to
      0.871 mSv per proton Gray for the large field snout. There is likely to be no
      excess risk to the fetus of severe mental retardation for a typical proton
      treatment of 80 Gray to the mother since the scattered neutron dose to the fetus
      of 69.7 mSv is well below the lower confidence limit for the threshold of 300 mGy
      observed for the occurrence of severe mental retardation in prenatally exposed
      Japanese atomic bomb survivors. However, based on the linear no threshold
      hypothesis, and this same typical treatment for the mother, the excess risk to
      the fetus of radiation induced cancer death in the first 10 years of life is 17.4
      per 10,000 children.

PMID- 16898452
TI  - Exploring breathing pattern irregularity with projection-based method.
AB  - Accurate descriptions of organ motion due to breathing are highly desirable for
      radiation treatment planning. This paper proposes an index that quantifies the
      irregularity of a signal related to respiratory motion. The method works by
      finding the periodic band-limited signal that best fits the signal samples, and
      then computing the root mean squared (RMS) residual error. The fitted signal
      itself may be useful for treatment planning. Using clinical data describing
      amplitude-time relationships (RPM, Varian) from twelve patients, we correlated
      the proposed index against relevant metrics from various treatment planning
      schemes. Simulation results demonstrate a reasonable match with all treatment
      methods considered, suggesting that the proposed irregularity index is suitable
      for a variety of treatment methods. Compared to the modified cosine function,
      which was investigated previously for breathing pattern models, the proposed
      approach is more representative, flexible, and computationally efficient.

PMID- 16898453
TI  - Rotating and static sources for gamma knife radiosurgery systems: Monte Carlo
      studies.
AB  - Rotating gamma systems (RGSs), GammaART-6000, and its Chinese equivalents, such
      as OUR and MASEP, etc., are new radiosurgery systems that use rotating 60Co
      sources instead of the 201 static sources (Leksell gamma knife, LGK). The
      rotating sources of RGSs simulate an infinite number of beams and promote
      extremely high target to surface dose ratios. However, the results of Monte Carlo
      in this study shows that RGS variants (modeled as having the same latitude
      angles, source to focus distance, and the distance from the source to the end of
      the collimator as the LGK) have smaller beam profile penumbra in the z direction,
      while LGK has smaller penumbra in the x and y directions. The differences are
      more significant in using larger collimators.

PMID- 16898455
TI  - Application of Gafchromic film in the dosimetry of an intravascular brachytherapy
      source.
AB  - The methodology of brachytherapy source dosimetry with Gafchromic MD 55-2 film
      (ISP Technologies, Inc.) is examined with an emphasis on the nonlinearity of the
      optical density-dose relation within the dynamic dose range, the radial distance
      dependent measurement uncertainty, and the format of data presentation. The
      specific source chosen for this study was a Checkmate (Cordis Corporation)
      intravascular brachytherapy system. The two-dimensional dose distribution around
      the source was characterized by a comprehensive analysis of measurement
      uncertainties. A comparative analysis of the dosimetric data from the vendor and
      from the scientific literature showed a substantial consistency of the
      information available for the Checkmate source. Our two-dimensional dosimetric
      data for the Checkmate source trains is presented in the form of measured along
      and away dose tables.

PMID- 16898454
TI  - Basic investigations on the performance of a normoxic polymer gel with tetrakis
      hydroxy-methyl-phosphonium chloride as an oxygen scavenger: reproducibility,
      accuracy, stability, and dose rate dependence.
AB  - Magnetic resonance (MR)-based polymer gel dosimetry using normoxic polymer gels,
      represents a new dosimetric method specially suited for high-resolution three
      dimensional dosimetric problems. The aim of this study was to investigate the
      dose response with regard to stability, accuracy, reproducibility, and the dose
      rate dependence. Tetrakis-hydroxy-methyl-phosphonium chloride (THPC) is used as
      an oxygen scavenger, and methacrylic acid as a monomer. Accuracy,
      reproducibility, and dose resolution were determined for MR protocols at low
      spatial resolution (typical for clinical scanners), medium, and microimaging
      resolution protocols at three different dose levels. The dose-response stability
      and preirradiation-induced variations in R2, related to the time interval between
      preparation and irradiation of the polymer gel, were investigated. Also
      postirradiation stability of the polymer gel was considered. These experiments
      were performed using a 60Co beam (E = 1.2 MV) in a water phantom. Moreover, we
      investigated the dose rate dependence in the low, medium, and saturation dose
      region of the normoxic polymer gel using a linear accelerator at photon energy of
      25 MV. MR scanning was performed on a 3 T whole body scanner (MEDSPEC 30/80,
      BRUKER BIOSPIN, Ettlingen, Germany) using several coils and different gradient
      systems adapted to the acquired spatial resolution investigated. For T2-parameter
      selective imaging and determination of the relaxation rate R2 = 1/T2, a multiple
      spin echo sequence with 20 equidistant echoes was used. With regard to
      preirradiation induced variations R2 increases significantly with the increasing
      time interval between the polymer gel preparation and irradiation. Only a slight
      increase in R2 can be observed for varying the postirradiation-time solely. The
      dose reproducibility at voxel volumes of about 1.4 x 1.4 x 2 mm3 is better than
      2%. The accuracy strongly depends on the calibration curve. THPC represents a
      very effective oxygen scavenger in methacrylic acid and gelatin. Polymer gels
      containing THPC offer high sensitivity to dose but their dose response also
      strongly depends on dose rate in the medium and high dose region.

PMID- 16898456
TI  - Peripheral doses from pediatric IMRT.
AB  - Peripheral dose (PD) data exist for conventional fields (> or = 10 cm) and
      intensity-modulated radiotherapy (IMRT) delivery to standard adult-sized
      phantoms. Pediatric peripheral dose reports are limited to conventional therapy
      and are model based. Our goal was to ascertain whether data acquired from full
      phantom studies and/or pediatric models, with IMRT treatment times, could predict
      Organ at Risk (OAR) dose for pediatric IMRT. As monitor units (MUs) are greater
      for IMRT, it is expected IMRT PD will be higher; potentially compounded by
      decreased patient size (absorption). Baseline slab phantom peripheral dose
      measurements were conducted for very small field sizes (from 2 to 10 cm). Data
      were collected at distances ranging from 5 to 72 cm away from the field edges.
      Collimation was either with the collimating jaws or the multileaf collimator
      (MLC) oriented either perpendicular or along the peripheral dose measurement
      plane. For the clinical tests, five patients with intracranial or base of skull
      lesions were chosen. IMRT and conventional three-dimensional (3D) plans for the
      same patient/target/dose (180 cGy), were optimized without limitation to the
      number of fields or wedge use. Six MV, 120-leaf MLC Varian axial beams were used.
      A phantom mimicking a 3-year-old was configured per Center for Disease Control
      data. Micro (0.125 cc) and cylindrical (0.6 cc) ionization chambers were
      appropriated for the thyroid, breast, ovaries, and testes. The PD was recorded by
      electrometers set to the 10(-10) scale. Each system set was uniquely calibrated.
      For the slab phantom studies, close peripheral points were found to have a higher
      dose for low energy and larger field size and when MLC was not deployed. For
      points more distant from the field edge, the PD was higher for high-energy beams.
      MLC orientation was found to be inconsequential for the small fields tested. The
      thyroid dose was lower for IMRT delivery than that predicted for conventional
      (ratio of IMRT/conventional ranged from 0.47-0.94) doses approximately [0.4-1.8
      cGy]/[0.9-2.9 cGy]/fraction, respectively. Prior phantom reports are for fields
      10 cm or greater, while pediatric central nervous system fields range from 4 to 7
      cm, and effectively much smaller for IMRT (2-6 cm). Peripheral dose in close
      proximity (< 10 cm from the field edge) is dominated by internal scatter;
      therefore, field-size differences overwhelm phantom size affects and increased
      MU. Distant peripheral dose, dominated by head leakage, was higher than
      predicted, even when accounting for MUs (approximtely factor of 3) likely due to
      the pediatric phantom size. The ratio of the testes dose ranged from 3.3-5.3 for
      IMRT/conventional. PD to OAR for pediatric IMRT cannot be predicted from large
      field full phantom studies. For regional OAR, doses are likely lower than
      predicted by existing "large field" data, while the distant PD is higher.

PMID- 16898457
TI  - Automated gamma knife radiosurgery treatment planning with image registration,
      data-mining, and Nelder-Mead simplex optimization.
AB  - Gamma knife treatments are usually planned manually, requiring much expertise and
      time. We describe a new, fully automatic method of treatment planning. The
      treatment volume to be planned is first compared with a database of past
      treatments to find volumes closely matching in size and shape. The treatment
      parameters of the closest matches are used as starting points for the new
      treatment plan. Further optimization is performed with the Nelder-Mead simplex
      method: the coordinates and weight of the isocenters are allowed to vary until a
      maximally conformal plan specific to the new treatment volume is found. The
      method was tested on a randomly selected set of 10 acoustic neuromas and 10
      meningiomas. Typically, matching a new volume took under 30 seconds. The time for
      simplex optimization, on a 3 GHz Xeon processor, ranged from under a minute for
      small volumes (<1000 cubic mm, 2-3 isocenters), to several tens of hours for
      large volumes (>30,000 cubic mm, >20 isocenters). In 8/10 acoustic neuromas and
      8/10 meningiomas, the automatic method found plans with conformation number equal
      or better than that of the manual plan. In 4/10 acoustic neuromas and 5/10
      meningiomas, both overtreatment and undertreatment ratios were equal or better in
      automated plans. In conclusion, data-mining of past treatments can be used to
      derive starting parameters for treatment planning. These parameters can then be
      computer optimized to give good plans automatically.

PMID- 16898458
TI  - Comparison of radiation shielding requirements for HDR brachytherapy using 169Yb
      and 192Ir sources.
AB  - 169Yb has received a renewed focus lately as an alternative to 192Ir sources for
      high dose rate (HDR) brachytherapy. Following the results of a recent work by our
      group which proved 169Yb to be a good candidate for HDR prostate brachytherapy,
      this work seeks to quantify the radiation shielding requirements for 169Yb HDR
      brachytherapy applications in comparison to the corresponding requirements for
      the current 192Ir HDR brachytherapy standard. Monte Carlo simulation (MC) is used
      to obtain 169Yb and 192Ir broad beam transmission data through lead and concrete.
      Results are fitted to an analytical equation which can be used to readily
      calculate the barrier thickness required to achieve a given dose rate reduction.
      Shielding requirements for a HDR brachytherapy treatment room facility are
      presented as a function of distance, occupancy, dose limit, and facility
      workload, using analytical calculations for both 169Yb and 192Ir HDR sources. The
      barrier thickness required for 169Yb is lower than that for 192Ir by a factor of
      4-5 for lead and 1.5-2 for concrete. Regarding 169Yb HDR brachytherapy
      applications, the lead shielding requirements do not exceed 15 mm, even in highly
      conservative case scenarios. This allows for the construction of a lead door in
      most cases, thus avoiding the construction of a space consuming, specially
      designed maze. The effects of source structure, attenuation by the patient, and
      scatter conditions within an actual treatment room on the above-noted findings
      are also discussed using corresponding MC simulation results.

PMID- 16898459
TI  - Evaluation of uncertainty predictions and dose output for model-based dose
      calculations for megavoltage photon beams.
AB  - In many radiotherapy clinics an independent verification of the number of monitor
      units (MU) used to deliver the prescribed dose to the target volume is performed
      prior to the treatment start. Traditionally this has been done by using methods
      mainly based on empirical factors which, at least to some extent, try to separate
      the influence from input parameters such as field size, depth, distance, etc. The
      growing complexity of modern treatment techniques does however make this approach
      increasingly difficult, both in terms of practical application and in terms of
      the reliability of the results. In the present work the performance of a model
      based approach, describing the influence from different input parameters through
      actual modeling of the physical effects, has been investigated in detail. The
      investigated model is based on two components related to megavoltage photon
      beams; one describing the exiting energy fluence per delivered MU, and a second
      component describing the dose deposition through a pencil kernel algorithm solely
      based on a measured beam quality index. Together with the output calculations,
      the basis of a method aiming to predict the inherent calculation uncertainties in
      individual treatment setups has been developed. This has all emerged from the
      intention of creating a clinical dose/MU verification tool that requires an
      absolute minimum of commissioned input data. This evaluation was focused on
      irregular field shapes and performed through comparison with output factors
      measured at 5, 10, and 20 cm depth in ten multileaf collimated fields on four
      different linear accelerators with varying multileaf collimator designs. The
      measurements were performed both in air and in water and the results of the two
      components of the model were evaluated separately and combined. When compared
      with the corresponding measurements the resulting deviations in the calculated
      output factors were in most cases smaller than 1% and in all cases smaller than
      1.7%. The distribution describing the calculation errors in the total dose output
      has a mean value of -0.04% and a standard deviation of 0.47%. In the dose
      calculations a previously developed correction of the pencil kernel was applied
      that managed to contract the error distribution considerably. A detailed analysis
      of the predicted uncertainties versus the observed deviations suggests that the
      predictions indeed can be used as a basis for creating action levels and tracking
      dose calculation errors in homogeneous media.

PMID- 16898460
TI  - Monte Carlo based IMRT dose verification using MLC log files and R/V outputs.
AB  - Conventional IMRT dose verification using film and ion chamber measurements is
      useful but limited with respect to the actual dose distribution received by the
      patient. The Monte Carlo simulation has been introduced as an independent dose
      verification tool for IMRT using the patient CT data and MLC leaf sequence files,
      which validates the dose calculation accuracy but not the plan delivery accuracy.
      In this work, we propose a Monte Carlo based IMRT dose verification method that
      reconstructs the patient dose distribution using the patient CT, actual beam data
      based on the information from the record and verify system (R/V), and the MLC log
      files obtained during dose delivery that record the MLC leaf positions and MUs
      delivered. Comparing the Monte Carlo dose calculation with the original IMRT plan
      using these data simultaneously validates the accuracy of both the IMRT dose
      calculation and beam delivery. Such log file based Monte Carlo simulations are
      expected to be employed as a useful and efficient IMRT QA modality to validate
      the dose delivered to the patient. We have run Monte Carlo simulations for eight
      IMRT prostate plans using this method and the results for the target dose were
      consistent with the original CORVUS treatment plans to within 3.0% and 2.0% with
      and without heterogeneity corrections in the dose calculation. However,
      significant dose deviations in nearby critical structures have been observed. The
      results showed that up to 9.0% of the bladder dose and up to 38.0% of the rectum
      dose, to which leaf position errors were found to contribute <2%, were
      underestimated by the CORVUS treatment planning system. The concept of average
      leaf position error has been defined to analyze MLC leaf position errors for an
      IMRT plan. A linear correlation between the target dose error and the average
      position error has been found based on log file based Monte Carlo simulations,
      showing that an average position error of 0.2 mm can result in a target dose
      error of about 1.0%.

PMID- 16898461
TI  - Temperature distribution and blood perfusion response in rat brain during
      selective brain cooling.
AB  - A rat model was used in this study to examine the transient temperature
      distribution and blood flow response in the brain during selective brain cooling
      (SBC) and rewarming. SBC was induced by a head cooling helmet with circulating
      water of 18 degrees C or 0 degrees C. It has been shown that the brain
      temperature reductions were 1.7+/-0.2 degrees C (5 mm beneath the brain surface)
      and 3.2+/-1.1 degrees C (2 mm beneath the brain surface) when the temperature of
      the water was 18 degrees C (moderate cooling). The cooling of the brain tissue
      was more evident when the circulating water was colder (0 degrees C, deep
      cooling). The characteristic time that it took for the tissue temperatures to
      reach a new steady state after the initiation of cooling varied from 5 to more
      than 35 min and it depended strongly on the blood flow response to the cooling.
      We used an ultrasound flow meter to measure continuously the blood flow rate in
      the common carotid artery during the cooling and rewarming. The blood flow rate
      dropped by up to 22% and 44% during the cooling from its baseline in the moderate
      cooling group and in the deep cooling group, respectively. Although all brain
      temperatures recovered to their baseline values 50 min after the helmet was
      removed, the blood flow rate only recovered to 92% and 77% of its baseline values
      after the moderate and deep cooling, respectively, implying a possible mismatch
      between the blood perfusion and metabolism in the brain. The current experimental
      results can be used to study the feasibility of inducing brain hypothermia by SBC
      if the blood flow responses in the rat are applicable to humans. The simultaneous
      recordings of temperature and blood flow rate in the rat brain can be used in the
      future to validate the theoretical model developed previously.

PMID- 16898462
TI  - Joint two-view information for computerized detection of microcalcifications on
      mammograms.
AB  - We are developing new techniques to improve the accuracy of computerized
      microcalcification detection by using the joint two-view information on
      craniocaudal (CC) and mediolateral-oblique (MLO) views. After cluster candidates
      were detected using a single-view detection technique, candidates on CC and MLO
      views were paired using their radial distances from the nipple. Candidate pairs
      were classified with a similarity classifier that used the joint information from
      both views. Each cluster candidate was also characterized by its single-view
      features. The outputs of the similarity classifier and the single-view classifier
      were fused and the cluster candidate was classified as a true microcalcification
      cluster or a false-positive (FP) using the fused two-view information. A data set
      of 116 pairs of mammograms containing microcalcification clusters and 203 pairs
      of normal images from the University of South Florida (USF) public database was
      used for training the two-view detection algorithm. The trained method was tested
      on an independent test set of 167 pairs of mammograms, which contained 71 normal
      pairs and 96 pairs with microcalcification clusters collected at the University
      of Michigan (UM). The similarity classifier had a very low FP rate for the test
      set at low and medium levels of sensitivity. However, the highest mammogram-based
      sensitivity that could be reached by the similarity classifier was 69%. The
      single-view classifier had a higher FP rate compared to the similarity
      classifier, but it could reach a maximum mammogram-based sensitivity of 93%. The
      fusion method combined the scores of these two classifiers so that the number of
      FPs was substantially reduced at relatively low and medium sensitivities, and a
      relatively high maximum sensitivity was maintained. For the malignant
      microcalcification clusters, at a mammogram-based sensitivity of 80%, the FP
      rates were 0.18 and 0.35 with the two-view fusion and single-view detection
      methods, respectively. When the training and test sets were switched, a similar
      improvement was obtained, except that both the fusion and single-view detection
      methods had superior test performances on the USF data set than those on the UM
      data set. Our results indicate that correspondence of cluster candidates on two
      different views provides valuable additional information for distinguishing FPs
      from true microcalcification clusters.

PMID- 16898463
TI  - Three dimensional radiation dosimetry in lung-equivalent regions by use of a
      radiation sensitive gel foam: proof of principle.
AB  - A polymer hydrogel foam is proposed as a potential three dimensional experimental
      dosimeter for radiation treatment verification in low-density tissue such as the
      lung. A gel foam is created by beating a radiation sensitive polymer gel mixture
      in an anoxic atmosphere. The mass density of the gel foam is in the order of 0.25
      0.35 kg/dm3. Both nuclear magnetic resonance (NMR) spin-spin relaxation rate (R2)
      and magnetization transfer ratio (MTR) have been used to map the dose
      distribution from the gel dosimeter. It is found that MTR has significant
      advantages compared to R2 for mapping the dose distribution in the polymer gel
      foam dosimeters. The magnetization transfer ratio is found to be less dependent
      on the density and microstructure of the gel foam dosimeter while spin-spin
      relaxation dispersion has been observed making the spin-spin relaxation rate
      dependent on the interecho time interval. Optical microscopy reveals a
      microstructure that shows great similarity with human lung tissue. It is also
      shown how NMR hydrogen proton density measurements can be used to map the density
      distributions in gel dosimeters.

PMID- 16898464
TI  - Real-time tumor tracking using implanted positron emission markers: concept and
      simulation study.
AB  - The delivery accuracy of radiation therapy for pulmonary and abdominal tumors
      suffers from tumor motion due to respiration. Respiratory gating should be
      applied to avoid the use of a large target volume margin that results in a
      substantial dose to the surrounding normal tissue. Precise respiratory gating
      requires the exact spatial position of the tumor to be determined in real time
      during treatment. Usually, fiducial markers are implanted inside or next to the
      tumor to provide both accurate patient setup and real-time tumor tracking.
      However, current tumor tracking systems require either substantial x-ray exposure
      to the patient or large fiducial markers that limit the value of their
      application for pulmonary tumors. We propose a real-time tumor tracking system
      using implanted positron emission markers (PeTrack). Each marker will be labeled
      with low activity positron emitting isotopes, such as 124I, 74As, or 84Rb. These
      isotopes have half-lives comparable to the duration of radiation therapy (from a
      few days to a few weeks). The size of the proposed PeTrack marker will be 0.5-0.8
      mm, which is approximately one-half the size of markers currently employed in
      other techniques. By detecting annihilation gammas using position-sensitive
      detectors, multiple positron emission markers can be tracked in real time. A
      multimarker localization algorithm was developed using an Expectation
      Maximization clustering technique. A Monte Carlo simulation model was developed
      for the PeTrack system. Patient dose, detector sensitivity, and scatter fraction
      were evaluated. Depending on the isotope, the lifetime dose from a 3.7 MBq
      PeTrack marker was determined to be 0.7-5.0 Gy at 10 mm from the marker. At the
      center of the field of view (FOV), the sensitivity of the PeTrack system was 240
      320 counts/s per 1 MBq marker activity within a 30 cm thick patient. The
      sensitivity was reduced by 45% when the marker was near the edge of the FOV. The
      scatter fraction ranged from 12% (124I, 74As) to 16% (84Rb). In addition, four
      markers (labeled with 124I) inside a 30 cm diameter water phantom were simulated
      to evaluate the feasibility of the multimarker localization algorithm.
      Localization was considered successful if a marker was localized to within 2 mm
      from its true location. The success rate of marker localization was found to
      depend on the number of annihilation events used and the error in the initial
      estimate of the marker position. By detecting 250 positron annihilation events
      from 4 markers (average of 62 events per marker), the marker success rates for
      initial errors of +/-5, +/-10, and +/-15 mm were 99.9%, 99.6%, and 92.4%,
      respectively. Moreover, the average localization error was 0.55 (+/-0.27) mm,
      which was independent of initial error. The computing time for localizing four
      markers was less than 20 ms (Pentium 4, 2.8 GHz processor, 512 MB memory). In
      conclusion, preliminary results demonstrate that the PeTrack technique can
      potentially provide real-time tumor tracking with low doses associated with the
      marker's activity. Furthermore, the small size of PeTrack markers is expected to
      facilitate implantation and reduce patient risk.

PMID- 16898465
TI  - Automated classification of hyperlucency, fibrosis, ground glass, solid, and
      focal lesions in high-resolution CT of the lung.
AB  - An automatic method for textural analysis of complete HRCT lung slices is
      presented. The system performs classification of regions of interest (ROIs) into
      one of six classes: normal, hyperlucency, fibrosis, ground glass, solid, and
      focal. We propose a novel method of automatically generating ROIs that contain
      homogeneous texture. The use of such regions rather than square regions is shown
      to improve performance of the automated system. Furthermore, the use of two
      different, previously published, feature sets is investigated. Both feature sets
      are shown to yield similar results. Classification performance of the complete
      system is characterized by ROC curves for each of the classes of abnormality and
      compared to a total of three expert readings by two experienced radiologists. The
      different types of abnormality can be automatically distinguished with areas
      under the ROC curve that range from 0.74 (focal) to 0.95 (solid). The kappa
      statistics for intraobserver agreement, interobserver agreement, and computer
      versus observer agreement were 0.70, 0.53+/-0.02, and 0.40+/-0.03, respectively.
      The question whether or not a class of abnormality was present in a slice could
      be answered by the computer system with an accuracy comparable to that of
      radiologists.

PMID- 16898466
TI  - Numerical simulations of phase contrast velocity mapping of complex flows in an
      anatomically realistic bypass graft geometry.
AB  - Combined in vitro experiments and numerical simulations were performed to study
      flow artifacts in phase contrast (PC) velocity mapping of steady flow through an
      anatomically realistic aortocoronary bypass graft model. The geometry was
      obtained through imaging and computational reconstruction of a left anterior
      descending (LAD) coronary artery of a porcine heart. Simulated images of through
      plane velocity were obtained at selected slices of the geometry. These were then
      compared and contrasted with velocity images of corresponding sites that were
      obtained from in vitro experiments. The shift and distortion of the measured
      velocity profile was well predicted by the simulation, while trajectories
      obtained from particle tracking were shown to be useful in understanding the
      origins of the flow artifacts that were observed.

PMID- 16898467
TI  - Reducing respiratory motion artifacts in positron emission tomography through
      retrospective stacking.
AB  - Respiratory motion artifacts in positron emission tomography (PET) imaging can
      alter lesion intensity profiles, and result in substantially reduced activity and
      contrast-to-noise ratios (CNRs). We propose a corrective algorithm, coined
      "retrospective stacking" (RS), to restore image quality without requiring
      additional scan time. Retrospective stacking uses b-spline deformable image
      registration to combine amplitude-binned PET data along the entire respiratory
      cycle into a single respiratory end point. We applied the method to a phantom
      model consisting of a small, hot vial oscillating within a warm background, as
      well as to 18FDG-PET images of a pancreatic and a liver patient. Comparisons were
      made using cross-section visualizations, activity profiles, and CNRs within the
      region of interest. Retrospective stacking was found to properly restore the
      lesion location and intensity profile in all cases. In addition, RS provided CNR
      improvements up to three-fold over gated images, and up to five-fold over ungated
      data. These phantom and patient studies demonstrate that RS can correct for
      lesion motion and deformation, while substantially improving tumor visibility and
      background noise.

PMID- 16898468
TI  - Computer-aided diagnostic scheme for the detection of lung nodules on chest
      radiographs: localized search method based on anatomical classification.
AB  - We developed an advanced computer-aided diagnostic (CAD) scheme for the detection
      of various types of lung nodules on chest radiographs intended for implementation
      in clinical situations. We used 924 digitized chest images (992 noncalcified
      nodules) which had a 500 x 500 matrix size with a 1024 gray scale. The images
      were divided randomly into two sets which were used for training and testing of
      the computerized scheme. In this scheme, the lung field was first segmented by
      use of a ribcage detection technique, and then a large search area (448 x 448
      matrix size) within the chest image was automatically determined by taking into
      account the locations of a midline and a top edge of the segmented ribcage. In
      order to detect lung nodule candidates based on a localized search method, we
      divided the entire search area into 7 x 7 regions of interest (ROIs: 64 x 64
      matrix size). In the next step, each ROI was classified anatomically into apical,
      peripheral, hilar, and diaphragm/heart regions by use of its image features.
      Identification of lung nodule candidates and extraction of image features were
      applied for each localized region (128 x 128 matrix size), each having its
      central part (64 x 64 matrix size) located at a position corresponding to a ROI
      that was classified anatomically in the previous step. Initial candidates were
      identified by use of the nodule-enhanced image obtained with the average radial
      gradient filtering technique, in which the filter size was varied adaptively
      depending on the location and the anatomical classification of the ROI. We
      extracted 57 image features from the original and nodule-enhanced images based on
      geometric, gray-level, background structure, and edge-gradient features. In
      addition, 14 image features were obtained from the corresponding locations in the
      contralateral subtraction image. A total of 71 image features were employed for
      three sequential artificial neural networks (ANNs) in order to reduce the number
      of false-positive candidates. All parameters for ANNs, i.e., the number of
      iterations, slope of sigmoid functions, learning rate, and threshold values for
      removing the false positives, were determined automatically by use of a bootstrap
      technique with training cases. We employed four different combinations of
      training and test image data sets which was selected randomly from the 924 cases.
      By use of our localized search method based on anatomical classification, the
      average sensitivity was increased to 92.5% with 59.3 false positives per image at
      the level of initial detection for four different sets of test cases, whereas our
      previous technique achieved an 82.8% of sensitivity with 56.8 false positives per
      image. The computer performance in the final step obtained from four different
      data sets indicated that the average sensitivity in detecting lung nodules was
      70.1% with 5.0 false positives per image for testing cases and 70.4% sensitivity
      with 4.2 false positives per image for training cases. The advanced CAD scheme
      involving the localized search method with anatomical classification provided
      improved detection of pulmonary nodules on chest radiographs for 924 lung nodule
      cases.

PMID- 16898469
TI  - New role for trusts in detecting rogue doctors.

PMID- 16898470
TI  - How the push for local choice in childbirth is foundering.

PMID- 16898471
TI  - On questioning commissioning.

PMID- 16898472
TI  - Data briefing. A&E admissions by diagnosis and SHA.

PMID- 16898473
TI  - The temps barrier.

PMID- 16898474
TI  - [A new view on kidney diseases in the light of advances in clinical genetics].

PMID- 16898475
TI  - [Progress in the treatment of secondary hyperparathyroidism. Role of
      calcimimetics].
AB  - Calcium-phosphate balance abnormalities, present in chronic renal failure since
      its early stages, are responsible for their negative impact on bones and
      cardiovascular system which increases patients morbidity and mortality. Phosphate
      retention, the strong stimulator of PTH secretion, plays the main role in calcium
      phosphate disturbances. The present paper reviews clinical experience with
      currently available phosphate binders and therapeutic strategies used in the
      treatment of secondary hyperparathyroidism. Special attention was paid to the new
      group of drugs namely calcimimetics, with emphasis on the first registered drug
      from this group cinacalcet. Mechanism of its' action, influence of the drug on
      calcium-phosphate balance parameters, safety profile, as well as the most
      frequent adverse effects are discussed in the present review.

PMID- 16898476
TI  - [The genetic background of congenital nephrotic syndrome].

PMID- 16898477
TI  - Nephrotic syndrome in children: should we always use steroids for the initial
      therapy?

PMID- 16898478
TI  - [The genetic background of haemolytic-uraemic syndrome].

PMID- 16898479
TI  - [Nephropathies of adolescence--the issue for the pediatrician and the internist].
AB  - Apart from the kidney diseases typical for early childhood, which (at least when
      clinically active) are entirely covered by pediatricians, there are several other
      nephropathies which occur predominantly in the period of adolescence and may be
      of potential interest for internist. In this review some clinical and therapeutic
      aspects of certain nephropathies of adolescence were discussed, namely lupus
      nephritis, Henoch-Schoenlein purpura nephritis, and the renal involvement in
      small vessel vasculitis. Medical and psychological problems that may arise not
      only from the presence of chronic disease, but also from the treatment side
      effects and difficulties in transition from pediatrician to internist were
      emphasized. Finally, certain circumstances and standards of smooth and
      comfortable transition of adolescent patient from pediatric to 'adult'
      nephrologist were proposed.

PMID- 16898480
TI  - [Is persistent arterial hypertension in patients on renal replacement therapy
      still an indication for bilateral native nephrectomy?].
AB  - Arterial hypertension (AHT) is common clinical symptom in 80% of patients at
      start of chronic dialysis and at 1 year remains overt in 50% of hemodialyzed and
      30% of patients on peritoneal dialysis. The incidence of AHT post-transplant is
      58% in long-term follow-up. The mechanism of AHT is complex, however in dialyzed
      patients the most common factor is (overt or hidden) fluid overload (volume
      dependent AHT). It develops as a consequence of inadequate evaluation of body dry
      mass and/or insufficient dialysis technique. Post-transplant AHT may develop as
      side-effect of long-term calcineurine inhibitors and steroid therapy and/or high
      renin production by native kidneys. In patients with chronic allograft
      nephropathy complex pathology of renal failure becomes more important factor. The
      data concerning efficacy of bilateral native nephrectomy are inconsistent.
      NAPRTCS survey data show, that incidence of AHT is similar in nephrectomized and
      non-nephrectomized patients up to 5 years post-transplant. In nephrectomized
      dialyzed patients fluid overload is still a main cause of AHT. Many therapeutic
      modalities, both pharmacological and dialysis-related, are available to improve
      blood pressure regulation. Bilateral native nephrectomy should be regarded as the
      last option, mostly in patients with ongoing renal co-morbidities, such as heavy
      proteinuria or recurrent urinary tract infection.

PMID- 16898481
TI  - [Influence of obesity in children on kidney].
AB  - According to the WHO report the rapid increase of obesity in adults and children
      is noted in developing and developed countries, resulting the epidemic state.
      Overweight (obesity) is noted in 50% adults; among children and teens aged 6-19
      years, 16% of them are considered as overweight. The adipose tissue is a large
      endocrine organ secreting biologically active substances as leptin, adiponectin
      and many growth factors regulating lipids metabolism. Obesity is associated with
      many complications as: hypertension, dyslipidemia, hyperglycemia (insulin
      resistance, glomerular hyperperfusion and hyperfiltration resulting renal injury
      with proteinuria) "obesity related glomerulopathy". The excess body weight in
      children may be a risk factor for kidney damage.

PMID- 16898482
TI  - [Cystinosis--an orphan disease. Pathogenesis and current treatment].
AB  - Cystinosis belongs to, so called, orphan diseases. It is an autosomal recessive
      lysosomal storage disease caused by defective transport of the amino acid cystine
      out of lysosomes. The stored cystine is poorly soluble and crystallizes within
      the lysosomes of many cell types, leading to widespread tissue and organ damage.
      Patients with the infantile nephropathic form of cystinosis (the most common and
      the most severe) develop symptoms early on in life and renal failure by late
      childhood. The current opinion about pathogenesis and treatment of the disease is
      described.

PMID- 16898483
TI  - [Polymorphism I/D of the angiotensin-converting enzyme gene and disturbance of
      blood pressure in type 1 diabetic children and adolescents].
AB  - AIM: The aim of the study was to evaluate an association between ACE genotypes
      and blood pressure (BP) disturbances in children and adolescents withType 1
      diabetes mellitus. MATERIALS AND METHODS: 126 normo-albuminuric, type 1 diabetic
      children and adolescents at the age 10.5-19.7 years, and duration of diabetes 2.0
      17.8 years, were included in the study. All patients were clinically normotensive
      and normoalbuminuric. Twenty-four-hour ambulatory BP monitoring was undertaken in
      all patients. The values of systolic BP, diastolic BP, mean arterial BP blood
      pressure and diurnal variation in BP were estimated. Prehypertension was
      diagnosed as BP values between 90pc or 120/80 mmHg and 95pc. ACE genotypes were
      assessed using polymerase chain reaction. RESULTS: In 48 individuals (38.1%)
      prehypertension was diagnosed. ACE genotypes distributed in patients were as
      follow: 31 (24.6%) genotype II, 45 (35.7%)--ID, and 50 (39.7%)--DD. Patients with
      DD genotype had higher nocturnal systolic BP (104 vs. 101 mmHg; p=0.029),
      diastolic BP (54 vs. 52 mmHg, p=0.003) and mean arterial BP (71 vs. 68 mmHg,
      p=0.003) as compared to carriers of the I allele (group ID + II). In the group DD
      in compare to the group ID + II lower nocturnal depletion in diastolic BP (18.0
      vs. 20.5 mmHg, p=0.024) and mean BP (14.8 vs 16.6 mmHg, p=0.049) was observed.
      14% patients of the DD group were non-dipper and 1.32% in the group ID + II
      (p=0.01). There was no differences in the prevalence of prehypertension between
      genotype groups (II+ID vs. DD: 38.2 vs. 38.0%, ns). CONCLUSIONS: Genotype DD is
      associated with nocturnal BP abnormalities in normotensive and normo-albuminuric
      children and adolescents with type 1 diabetes. There is no relationship between
      frequency of prehypertension and ACE gene polymorphism.

PMID- 16898484
TI  - [LAMB2 gene mutation as a cause of congenital nephrotic syndrome with distinct
      eye abnormalities and hypotonia].
AB  - Mutations in the LAMB2 gene encoding laminin beta2, a component of the glomerular
      basement membrane and the neuro-muscular junction are responsible for the
      characteristic renal and eye abnormalities of Pierson syndrome. We report a girl
      with confirmed LAMB2 mutation who presented with early onset Congenital Nephrotic
      Syndrome (CNS) with renal failure and ocular findings of bilateral microcoria,
      persistent hyperplastic primary vitreous, right microphtalmia and left eye
      cataract. Automated peritoneal dialysis was started from the 3rd month of life.
      Severe muscle hypotonia with motor and mental delay were observed during the
      first year of life. She experienced numerous serious infections from birth and
      died at the age of 15 months due to a fulminant infection. Genetic studies
      revealed two novel mutations in LAMB2 gene (compound heterozygosity).
      CONCLUSIONS: 1. Mutations in LAMB2 gene should be included in the work-up of
      patients with CNS in the presence of eye anomalies. 2. Severe phenotypes of
      Pierson syndrome are associated with marked handicaps and a poor outcome.

PMID- 16898485
TI  - [The role of some selected risk factors in the development of the nephrotoxicity
      of immunosuppressive medications used after the heart transplantation in children
      and young adults].
AB  - The goal of this research was the assessment of non-genetic and genetic risk
      factors of renal lesions in children after heart transplants. The research was
      carried out in 22 pediatric heart transplant recipients who have had a long-term
      treatment with calcineurin inhibitors. Renal function was assessed directly after
      the transplantation and then in 3 months intervals with the monitoring of
      calcineurin inhibitors concentration in the plasma. A significant renal lesion
      has been confirmed, which was a time-function in all examined patients, although
      its severity varied. Acute renal insufficiency, transplant rejection and ATG
      usage in the peri-transplant and the post-transplant periods have not proven to
      influence the complications mentioned above. The relationship between "high
      TGFbeta production genotype" and the intensity of nephrotoxicity of calcineurin
      inhibitors has been confirmed.

PMID- 16898486
TI  - [Mycophenolate mofetil in treatment of childhood nephrotic syndrome--preliminary
      report].
AB  - The management of nephrotic syndrome (NS) in children remains a clinical
      challenge for pediatricians and pediatric nephrologists. Especially, the
      treatment of patients with steroid-resistant (SR) and steroid-dependent (SD)
      nephrotic syndrome, because they are at risk for developing complications from
      prolonged exposure to steroids, CsA and alkylating agents. Mycophenolate mofetil
      (MMF) is a selective and reversible inhibitor of inosine monophosphate
      dehydrogenase used above all in transplantology and recently also in patients
      with nephrotic syndrome. The aim of this study was to tentatively assess the
      usefulness and the safety of MMF as an immunosuppressive agent in children with
      steroid-resistant NS, in whom remission was not obtained with previous treatment
      regimens, and those with steroid-dependent NS, in whom severe adverse reactions
      were observed in steroid and cyclosporine therapy. The study included 19 children
      with NS (11 girls, 8 boys) aged 7 to 19.5 years (a mean of 13.5), treated at the
      Deptartment of Pediatric Nephrology. The duration of disease was from 1 to 16
      years (a mean of 9.3). The patients were divided into 3 groups: I--9 children
      with steroid-dependent NS; II--6 children with steroid-dependent NS and episodes
      of steroid-resistance; III--4 children with steroid-resistant NS. All patients in
      groups II and III required multi-drug therapy (prednisone, cyclosporine A,
      methylprednisolone, chlorambucil, cyclophosphamide) before MMF was introduced.
      MMF was administered orally: 180-600 mg/m2 body surface/dose, twice daily. The
      follow-up period lasted for 4 to 16 months (a mean of 7.7). The clinical outcome
      analysis included decrease or disappearance of proteinuria, clinical improvement
      and/or possibility of tapering therapy intensity, especially the dosage of
      steroids and/or CsA. Also, renal function was monitored with serum cystatine C
      concentration. Particular attention was paid to adverse effects of MMF upon the
      gastro- intestinal tract and/or opportunistic infections. All medication (apart
      from MMF) could be discontinued in 4 patients; in 15 cases, prednizone dose was
      reduced and in 9 cases CsA dose was reduced or discontinued. In group I (SD)
      steroid treatment could be reduced from a mean prednisone dose of 22.8 to 3.6
      mg/m2/48 hours (p=0.018), in groups II and III, in spite of 50 % reduction of a
      mean prednisone dose, the difference did not reach statistical significance.
      During MMF therapy Csa treatment could be reduced from a mean CsA dose 4.3 to 2.9
      mg/kg/24 hours (p=0.008). Improvement or preservation of stable renal function
      was observed in all patients--cystatin C levels decreased significantly from a
      mean 1.35 to 0.96 mg/l (p=0.007). Adverse reaction to MMF (abdominal pain) was
      observed in 2 patients (nausea, vomiting, diarrhoea in 1, CMV infection in 1).
      The initial clinical observation of MMF treatment in nephrotic patients shows its
      best effect in the group of patients with steroid-dependent NS. MMF can safely be
      used in children with NS. The introduction of MMF allows for reduction of other
      chronically used medications, especially CsA and steroids.

PMID- 16898487
TI  - [Fat tissue distribution and metabolic alterations in boys with primary
      hypertension].
AB  - Metabolic alterations related to obesity are regarded as significant risk factor
      for target organ damage in hypertensive patients. Fat tissue distribution seems
      to play significant role in metabolic alterations related to cardiovascular
      damage. The aim of the study was to test hypothesis that fat tissue distribution
      and excess of visceral fat is related to cardiovascular damage and metabolic
      cardiovascular risk factors in obese boys with yet untreated, primary
      hypertension. PATIENTS: 40 boys (14.8 +/- 3.0 yrs) with untreated essential
      hypertensions. METHODS: amount of visceral (VAT), intraperitoneal visceral
      (ipVAT), extraperitoneal visceral (epVAT) and subcutaneous fat (SAT) was measured
      by nuclear magnetic imaging (NMR). Carotic intima media thickness (cIMT), fenoral
      intima media thickness (fIMT) and left ventricular mass index (LVMi) were
      evaluated by sonography. Oral glucose loading test was done, lipids,
      homocysteine, CRP, uric acid, microalbuminuria, adipocytokines, IGF-1 and IGF
      binding proteins (IGFBP) were determined. RESULTS: The ratio of VAT to epVAT
      (V/Ve) correlated with carotid IMT (p=0.0001; r=0.561), standard deviation from
      median of the norm of cIMT (cIMT-SDS) (p=0.0001; r=0.681), femoral IMT (p=0.015;
      r=0.480) and fIMT-SDS (p=0.002; r=0.579). SAT correlated negatively with cIMT
      (p=0.0016; r=-0.355) and cIMT-SDS (p=0.01; r=-0.391). Waist to hip ratio (WHR)
      correlated with cIMT-SDS (p=0.03; r=0.401). VAT correlated positively and SAT
      negatively with HDL, apoA1, uric acid concentration and HOMA-IR value. VAT/epVAT
      correlated with HOMA-IR (p=0.02; r=0.402), free IGF-1 (p=0.001; r=0.478). epVAT
      also correlated with free IGF-1 (p=0.006; r=-0.494) and IGFBP3 (p=0.02; r=
      0.471). Step-wise regression analysis revealed that relative excess of
      intraperitoneal visceral fat (VAT/epVAT) and WHR were independent predictors of
      cIMT-SDS(p=0.022, R2=0.755). CONCLUSIONS: Fat tissue distribution correlates with
      early vascular injury and metabolic alterations in boys with primary
      hypertension. Relative excess of visceral fat assessed by NMR and truncal obesity
      expressed as WHR are independent risk factors for early vascular damage in
      overweight boys with primary hypertension.

PMID- 16898488
TI  - [Fetuin A in children with renal diseases].
AB  - Fetuin A, 59 kDa protein, produced in the liver is a circulating inhibitor of
      vascular calcification. The aim of the study was to estimate a concentration of
      fetuin A in children with renal diseases. Fifty three children were examined: 18
      with idiopathic nephrotic syndrome (NS) aged 2.5 to 14.5 years, mean 6.6 +/- 3.6
      and 35 with chronic renal failure (CRF) aged 4.5 to 20 years, mean 13.3 +/- 3.9.
      The control group (K) consisted of 22 healthy children, aged from 6.5 to 17.5
      years, mean 10.8 +/- 3.3. In all children serum concentration of fetuin A (ELISA
      method, BioVendor), calcium (sCa), phosphorus (sP), protein (P), albumin (Alb),
      total cholesterol (TC) and triglycerides (TG) were measured. The daily protein
      excretion in children with proteinuria (mg/kg/day) and the serum parathormone
      (PTH) level in children with CRF were analysed. RESULTS: The concentration of
      fetuin A was the lowest in children with NS (78.1 +/- 24.5 ng/ml) and was
      statistically different (p=0.0003) than in group K (101.4 +/- 11 ng/ml) and group
      CRF (106.7 +/- 13.7 ng/ml). In group NS significant correlations were found
      between concentrations of fetuin A and sCa (r=0.62, p<0.01), P (r=0.59, p= 0.01)
      and Alb (r=0.64, p<0.01) and negative correlations with concentration of TC (r=
      0.68, p<0.01) and daily proteinuria (r=-0.79, p<0.001). In groups K and CRF the
      correlations of fetuin A level and analysed parameters were not found.
      CONCLUSION: Low concentration of fetuin A in children with nephrotic syndrome may
      be the additional agent to promote the atherogenic lesions.

PMID- 16898489
TI  - [Congenital and genetic related causes of end-stage renal disease--data from
      Polish Registry of Renal Rreplacement Therapy in Children 2000-2004].
AB  - One of the objectives of Polish Registry of Renal Replacement Therapy in Children
      established on 31st Dec. 2000 was to collect complete data on etiology of end
      stage renal disease (ESRD) in polish children. MATERIAL AND METHODS: Data on 469
      patients (251 boys, 218 girls) aged 0-22 years treated with renal replacement
      therapy (RRT) at 13 pediatric dialysis units in Poland from 2000 to 2004 were
      analyzed. The mean age at start of dialysis was 10 years and 3 months. Renal
      diseases were defined according to EDTA coding system. Data is presented for the
      whole group, in 5-year age groups and separately for both sexes. RESULTS:
      Congenital and genetic renal diseases were the cause of ESRF in 56% of the polish
      population of children and adolescents on RRT. 39% of causes were acquired
      diseases, 5% remained unidentified. Congenital and genetic causes dominated in
      children < 5 years of age (71%). They accounted for 49%, 61% and 45% of causes in
      the consecutive 5-year age groups. The most numerous group of congenital diseases
      leading to ESRF were uropathies 37% and 25% of causes in the consecutive age
      groups. In boys the most frequent uropathy was obstructive uropathy (25%), the
      majority caused by posterior urethral valves. In girls the most frequent
      uropathies were reflux nephropathy (10%) and nephropathy secondary to neurogenic
      bladder (9%). Uropathies were followed by renal hypo-dysplasia without urinary
      tract anomalies (11%) and cystic diseases (10%). CONCLUSIONS: Congenital kidney
      anomalies and genetic diseases are the leading cause of end-stage renal disease
      in children up to 15 years of age.

PMID- 16898490
TI  - [Antibodies against heat shock proteins (HSP) in children with chronic renal
      failure (CRF)--preliminary results].
AB  - Current data suggest the role of autoimmune reactions in the pathogenesis of
      cardiovascular complications in CRF patients. Elevated levels of anti-Hsp
      autoantibodies (anti-Hsp60, anti-Hsp70) have been described in adults with
      atherosclerotic lesions and cardiovascular events. The aim of the study was to
      evaluate the levels of anti-Hsp60 and anti-Hsp70 in sera of CRF children. Serum
      uric acid, lipid profile, erythrocyte sedimentation rate (ESR) and hsCRP were
      also estimated. MATERIAL AND METHODS: The study was performed on 18 CRF children
      treated conservatively, divided into 2 subgroups: 8 patients with serum
      creatinine levels below 265 micromol/l (gr. I) and 10 patients with serum
      creatinine levels above 265 micromol/l (gr. II). The control group consisted of
      13 healthy age-matched subjects with normal kidney function. Anti-Hsp
      concentrations were evaluated by ELISA, hsCRP levels--by nephelometry. RESULTS:
      There were no differences in median values of anti-Hsp60, anti-Hsp70 and total
      cholesterol (CHOL) between examined groups. Mean hsCRP levels were also
      comparable. No difference was seen when HDL-C and LDL-C levels in gr. I and
      control group were compared, whereas TGL concentrations were elevated in gr.I vs.
      controls (p<0.001). In gr. II HDL-C levels were lower vs. controls (p<0.01),
      whereas LDL-C and TGL concentrations were higher compared to controls (p<0.001,
      p<0.0001). LDL-C levels in gr.II were also elevated vs. gr. I (p<0.01). Anti
      Hsp70 correlated with serum uric acid (R=-0.82, p=0.04), cholesterol (R=-0.78,
      p=0.03), CHOL/LDL-C (R=-0.89, p=0.007) and CHOL/TGL (R=-0.75, p=0.03) in gr. I
      and with ESR after 1h in gr. II (R=0.72, p=0.03). No correlations were found
      between hsCRP and other parameters. CONCLUSIONS: Preliminary results point at
      relations between anti-Hsp70, markers of chronic inflammation (ESR) and
      atherosclerotic risk (uric acid, cholesterol) in CRF children.

PMID- 16898491
TI  - [The antioxidant therapy modulates intracellular lymphokine expression in
      children on dialysis].
AB  - Oxidative stress (SOX) is believed to be responsible for functional disabilities
      of lymphocytes in end-stage renal disease (ESRD). Therefore, we investigated the
      effect of antioxidant therapy with vitamin E and N-acetylcysteine (NAC) on SOX
      and cytokine synthesis in T cells in dialyzed children. Eighteen children (aged 2
      20, mean 10.9 yr) treated with hemodialysis (n=5) and peritoneal dialysis (n=13)
      were enrolled into the study. Vitamin E and NAC were given orally for six months.
      Throughout the study, intracellular lymphokines [interleukin (IL)-2, interferon
      (IFN)-gamma, IL-4, IL-6] and SOX in T cells were measured by means of flow
      cytometry. In dialyzed children, mean fluorescence intensity (MFI), which
      reflected intracellular SOX, was significantly higher than in the controls in
      both CD3+ and CD3+CD4+ cells (p<0.05). We also found a cytokine dysregulation
      with a trend toward a predominant T helper (Th)-1 response compared to the
      controls. After 6 months of treatment with antioxidants, a significant reduction
      in MFI was noted compared to baseline values in CD3+ and CD3+CD4- cells
      (p<0.001). Interestingly, the therapy led to a decrease in IFN-gamma as well as
      an increase in IL-4 and IL-6 production. In addition, a gradual decline in IFN
      gamma/IL-4 ratio in Th cells was noted. CONCLUSIONS: Vitamin E and NAC used in
      combination are effective in reducing the intracellular SOX, and besides their
      action on cellular redox state, they modulate the cytokine profile in children on
      dialysis.

PMID- 16898492
TI  - [Osteoprotegerin and calcium-phosphorus metabolism parameters in children with
      chronic renal failure].
AB  - Osteoprotegerin (OPG), a member of the TNF receptor superfamily is a natural
      inhibitor of osteoclastogenesis and important inhibitor of vascular
      calcification. The aim of the study was to estimate a correlation of serum OPG
      level and the other parameters calcium-phosphorus metabolism in children with
      chronic renal failure. Seventy four children with chronic renal insufficiency, 48
      on conservative treatment (CRF) aged 13 +/- 3 years with creatinine clearance 45
      +/- 21 ml/min/1.73m2 and 26 with end-stage renal disease (ESRD) aged 14 +/- 5
      years were examined. The control group (K) consisted of 23 healthy children aged
      10.8 +/- 3 years. In all children serum concentration of OPG, calcium (sCa),
      phosphorus (sP), PTH, CAP (cyclase activating PTH), CIP (cyclase inactive PTH)
      and osteocalcin (OC) were measured. OPG was determined by ELISA method
      (Biomedica), PTH and OC by IRMA (Duo-PTH, Scantibodies, USA and Osteo-Riact firm
      CIS, F). RESULTS: The concentration of OPG was higher in ESRD group (3 +/-1.6
      pmol/l) than in K (1.95 +/- 0.56 pmol/l), p<0.005. The concentration of OPG in
      CRF group (2.42 +/- 1.4 pmol/l) was not different from this in K and ESRD. The
      concentration of OPG did not correlate with serum creatinine level. In CRF group
      no correlation was found between OPG level and the other parameters, in group
      ESRD the significant correlation between OPG and OC was found (R=0.55, p=0.006).
      The level of OPG in children CRF + ESRD correlated with PTH concentration
      (R=0.27, p<0.03), CAP (R=0.29, p<0.02), CIP (R=0.23, p<0.05) and OC (R=0.25,
      P<0.04). In patients with higher PTH level (> 200 pg/ml) the higher correlations
      between OPG and PTH, CAP and CIP were found. No significant correlation between
      PTH and OPG in patients with lower PTH level (< 200 pg/ ml) was found. No
      significant correlation between OPG and OC in patients with lower and higher PTH
      was found. CONCLUSION: The elevated levels of OPG in children with ESRD may
      reflect the higher bone turnover in these patients.

PMID- 16898493
TI  - [Chronic peritoneal dialysis in infants--preliminary results of the multicenter
      survey].
AB  - We retrospectively analysed peritoneal dialysis treatment in 29 infants dialysed
      in 9 paediatric centres in Poland in the years 1993-2004. The mean age at the
      start of dialysis was 4.9 +/- 3.5 months (range 2 days to 11 months), mean body
      mass 5.6 +/- 2.5 kg (range 2.5 to 11 kg). The mean duration of PD was 6.8 +/- 3.9
      in the first year of life and total duration of the therapy 34 +/- 27 months. Of
      the 29 infants 4 died (2 in infancy), 11 underwent renal transplantation, in 2
      children PD was stopped (they received a conventional treatment) and 12 were
      still dialysed at the date of data collection. The peritonitis rate was 1/9.5
      patient-month and exit site infection rate 1/16 patient-month up to 1 year of
      life. 9 children (31%) required hernia repairs and in 9 catheters were replaced.
      Chronic peritoneal dialysis in infants is associated with high risk of infections
      and surgical complications and remains a challenge for paediatric nephrologists.

PMID- 16898494
TI  - [Peritoneal transport properties for glucose and creatinine in Polish children
      and adolescents on chronic peritoneal dialysis].
AB  - INTRODUCTION: The mode of PD treatment is dependent on the individual transport
      properties of the peritoneal membrane. Two multicentre trials performed in the
      U.S. (PPDSC) and Europe (MEPPS) have established reference curves for solute
      equilibration in children performed with the use of 1100 ml/m2 fill volume in the
      former and 1000 ml/m2 in the latter study. AIM OF THE STUDY: Assessment of basal
      peritoneal membrane equilibration based on PET tests in polish children and
      adolescents treated with chronic peritoneal dialysis. MATERIAL AND METHODS: 58
      PET tests from patients treated at 8 Polish PD centres were analysed. The mean
      time of performing PET test was 6,5 months after the start of PD therapy. All of
      the patients had been peritonitis free from onset. The mean fill volume was 1021
      (906-1170) ml/m2. RESULTS: Based on the results of creatinine and glucose
      equilibration we established basal peritoneal solute transport curves for polish
      PD children using an average fill volume of 1020 ml/m2. The following values were
      obtained at 4hrs of dwell time for 2.27% glucose solution: D/P for creatinine =
      0.68 +/- 0.15 and D/Do for glucose = 0.39 +/- 0.12. CONCLUSIONS: The DIP
      creatinine equilibration curves were similar to the previously published
      reference curves for children, whereas those for glucose was significantly lower.
      Using a fill volume scaled to body surface area of 1020 ml/m2 equilibration
      curves for glucose and creatinine are similar in children over 1 year of age and
      adults.

PMID- 16898495
TI  - [Continuous renal replacement therapy in children with acute renal failure--5
      years of experience].
AB  - Continuous renal replacement therapy (CRRT) has became a modality of choice in
      chidren with acute renal failure (ARF), especially in cases of multiorgan failure
      (MOF) and in hemodynamically unstable patients in whom regular hemodialysis is
      difficult to reform. Newborns and infants with contraindications to peritoneal
      dialysis are another group of patients treated with CRRT. Retrospective analysis
      of CRRT therapy in 112 patients treated with (CVVHD, CVVH, CVVHDF, SCUF
      continuous veno-venous hemodialysis/hemofiltration/
      hemodiafiltration/ultrafiltration) between 2000-2005 is presented. Indication to
      CRRT was MOF (n=23, 20%), complications post-liver transplant (n=33, 29%),
      congenital metabolic defects (n=5, 4.5%), complications of cancer or chemotherapy
      (n=11, 9.8%) and other causes of ARF (n=40, 36.7%). Overall mortality was 36.6%.
      The highest rate was seen in children between 0-2 years of age (52,3%) and in
      patients with congenital metabolic diseases (80%). When adjusted to specific
      modality--the highest mortality was seen in patients treated with CVVHF (55.4%),
      while lower was in cases treated with CVVHD (37.8%) and CVVHDF (35.4%). Among
      older children higher mortality was seen in patients with mean arterial pressure
      (MAP) <70 mmHg (68.4%), compared to patients with MAP >70 mmHg (23.1%).

PMID- 16898496
TI  - [Preliminary assessment of heart function in chronically dialysed children].
AB  - Renal replacement therapy has become a recognized treatment modality of children
      with chronic renal failure (CRF). Despite of unquestionable progress in
      heamodialysis treatment quite high morbidity and mortality still remain a serious
      problem among pediatric patients. The most common cause of death in haemodialyzed
      and transplanted patients are cardiovascular complications. The main aim of the
      study was an echocardiographic (ECHO) assessment of selected cardiac parameters
      in heamodialyzed children. METHODOLOGY: 16 chronically dialyzed (6 HD, 10 PD)
      children participated in the study (10 M, 6 F), aged 5-18,5 yrs (x=12.2 +/- 3.8
      yrs). Echocardiography examinations were carried out with HP 5500 device and S4
      ultrasound probe of variable frequency. Diastolic and systolic LV dimension,
      ejection fraction (EF) and LV mass index (LVMI) were evaluated. By means of
      pulsating Doppler method mitral flow peak E and A velocity and isovolumetric
      relaxation time (IRT) were assessed. RESULTS: On the basis of ECHO examinations 3
      groups were singled out: A (n=3) of normal heart function, B (n=3) of impaired
      systolic and diastolic heart function and C (n=10) of normal systolic and
      impaired diastolic heart function. In group of children with severe cardiac
      lesion (B group) a higher LV mass (A vs B vs C: 74.7 vs 119.9 vs 73.5 g/m2) and
      statistically significant lower ejection fraction (68.1 vs. 33.7 vs. 65.9%) were
      ascertained. These children were anuric (996 vs. 0 vs. 1112 mild), their systolic
      (102.1 vs. 118.4 vs. 117,9) and diastolic (64,4 vs. 84.8 vs. 77.9) blood pressure
      were significantly higher, so was the number or hipotensive medications (0.33 vs.
      1.72 vs. 1,44). CONCLUSIONS: The great majority of chronically dialyzed children
      demonstrates an impairment of cardiac function mainly of diastolic parameters.
      Anuria and hypertension stand for a significant risk factor of cardiac lesion.

PMID- 16898497
TI  - [Heterozygotic mutation in NPHS2 gene as a cause of familial steroid resistant
      nephrotic syndrome in two siblings--case report].
AB  - Within recent years the number of children with focal segmental
      glomerulonephritis (FSGS) has increased. A significant progress in defining of
      molecular basis of the disease has been made. Gene mutations for nephrin,
      podocin, WT1, alpha-actinin 4 cause the damage of filtration barrier of
      glomerulus and proteinuria in consequence. A girl (S.G.) became ill at the age of
      3.5, suffering form steroid-resistant nephritic syndrome (SRNS) with microscopic
      hematuria. The renal biopsy showed FSGS accompanied by a complete diffuse
      effacement of podocyte food processes. Despite intensive and regular
      immunosuppressive therapy, remission was not achieved. In the control renal
      biopsy performed a year after cyclosporin A had been applied, 50% of globally
      sclerosed glomeruli as well as some features of post-cyclosporin damage were
      found. The girl required renal replacement therapy at the age of 10.5. Dialyzed
      at the adult dialysis centre she died at the age of 11.5. A boy S.P. was
      diagnosed with SRNS when he was 11.5 years old. The renal biopsy was performed
      after one month of treatment and showed mesangial proliferation and diffuse
      effacement of podocyte food processes. After chlorambucil treatment remission was
      not achieved, and after methylprednisolon pulse therapy only the reduction of
      proteinuria was achieved. In a control renal biopsy 10 out of 13 glomeruli were
      globally sclerosed. At the age of 17 the patient showed chronic renal failure
      with a fast progression of the disease. In September 2000 the boy started renal
      replacement therapy, an in June 2001 he received a renal transplant without the
      recurrence of FGS. In 2001 a heterozygous mutation (A284V) in gene NPHS2 was
      found in both of the siblings. Within the confines of the clinical project ESCAPE
      Trial another genetic examination was performed. In the boy one missense mutation
      on one allele (A284V) and the R229Q polymorphism on the other allele were found.
      In this family the father is bear. ing the A284V mutation and the mother the
      R229Q variant. These results prove that this disease is due to alterations of the
      podocin gene in the described family.

PMID- 16898498
TI  - [Wilms tumor as a novel model of angiogenesis in childood nephropathies].
AB  - Wilms tumor has a unique possibility of recapitulation within its substance
      different stages of renal development. Vascular endothelial growth factor (VEGF)
      and its receptors (VEGFR-1 and VEGFR-2) are regarded to play the crucial role in
      the process of simultaneous development of tubules and glomeruli in animal
      kidney. Neoangiogenesis, secondary to rearrangement of epithelial elements in
      Wilms tumor, may therefore follow the lack of glomeruli in this neoplasm. The aim
      of the present research was an immunohistochemical analysis of VEGF-C and VEGFR-2
      expressions in Wilms tumor and an attempt of explanation of neovascularisation
      process in this malignancy. The study group was composed of 16 children diagnosed
      with Wilms tumor (stage III of clinical classification) hospitalised in
      Department of Paediatric Oncology, Hematology and Transplantology, University of
      Medical Sciences in Poznan. The indirect immunohistochemical assay with the use
      of monoclonal antibodies directed against VEGF-C and VEGFR-2 was employed. VEGF-C
      expression was detected within blastemal and hypocellular stromal components of
      Wilms tumor. On the other hand, immuno-reactivity of VEGFR-2 was established in
      dysplastic tubules in the closest proximity of VEGF-C positive parts of stromal
      origin. VEGF-C dependent neovascularisation in Wilms tumor may follow an adequate
      differentiation of already existing epithelial elements. It may also explain the
      process of glomeruli-dependent physiological development of kidney and, what is
      also probable, the phenomenon of neoangiogenesis described in individual
      childhood nephropathies.

PMID- 16898499
TI  - [Urinary fibronectin excretion as a marker of disease activity in children with
      IgA nephropathy and Henoch-Schonlein nephropathy].
AB  - The increase of extracellular matrix proteins synthesis including fibronectin
      (FN) is associated with development of renal sclerosis. The aim of the study was
      to examine urinary FN excretion as a marker of renal changes in patients (pts)
      with IgAN and HSN. The study group consisted of 34 children: IgAN n=11 and HSN
      n=23, mean age 12.44 +/- 3.83 years. At the onset of illness we observed
      erytrocyturia in all children, proteinuria in 28: nephrotic sydrome in 14 pts
      (IgAN--4, HSN--10) and proteinuria in 14 children (IgAN--6, HSN--8). In mean time
      0.6 years from the onset of illness renal biopsies were performed. Changes in
      light microscopy were graded I-V degrees according to the classification of WHO.
      FN was measured in 24-h urine collections (ng/mg of creatinine), using specific
      antibody (DAKO) and proteinuria (mg/24h). Mean time from the biopsies to examine
      FN was 0.76 +/- 1.16 years. FN excretion was analysed in 2 group pts: group A-
      with proteinuria (n=28); group B--with erytrocyturia (n=6). The control group (K)
      consisted of 14 healthy children. Renal function was normal in all. RESULTS: The
      FN concentration higher than normal we observed in 22 pts (78.6%) in group A and
      3 (50%) in group B. Mean FN value A was higher (NS) 274 +/- 213.0 than in B 132.0
      +/- 68.8 and significant (p<0.01) than in group K (59.9 +/- 31.3). We found a
      positive correlation between FN and proteinuria in the moment of measurement the
      FN concentration (p=0.01, r=0.51). The higher values of FN (NS) we observed in
      pts with higher proteinuria at the onset of illness. FN excretion was
      significantly eleveted in younger children (p<0.001, r=-0,58). We not found a
      correlation between mean FN value and the grade of changes in renal biopsies
      (WHO). CONCLUSION: Urinary FN excretion may be a marker of disease activity in
      children with IgAN and HSN.

PMID- 16898501
TI  - [Immunohistochemical analysis of podocytopathy with immature glomeruli and
      glomerulosclerosis in children with nephrotic syndrome].
AB  - Idiopathic nephrotic syndrome in children may be complicated by resistance to
      steroids with constant proteinuria in diffuse mesangial proliferation (DMP) and
      focal segmental glomerulosclerosis (FSGS). In our observation, sometimes in
      children with steroid-resistant nephrotic syndrome, the presence of immature
      renal glomeruli can be detected (hypercellularity and presence of a constant
      layer of cubical epithelial cells on the surface of glomerular tufts, without
      sclerosis, resembling M-stage of glomerulo-genesis). The aim of this study was
      immunohistochemical analysis of the podo-cyte-associated proteins, particularly
      ezrin, podocalyxin, synaptopodin and nephrin in glomeruli with and without signs
      of immaturity in children. In DMP with signs of immaturity podo-cytes situated in
      the central region of the glomerulus were immunohistochemically negative. The
      positive reaction was observed exclusively in the most superficial continuous
      'layer' of podo-cytes. The unfavourable clinical course of nephrotic syndrome
      with signs of glomerular immaturity may be a consequence of decreased
      immunohistochemical expression of cytoskeleton-specific proteins.

PMID- 16898500
TI  - [Urinary TGF-beta1 excretion in children with renal cysts].
AB  - Autosomal dominant polycystic disease is characterised by abnormal polycystin,
      protein, which is a component of basement membrane and extracellular matrix.
      Transforming growth factor (TGF-beta1) is a cytokine, which takes part in
      development of renal tubule epithelium and stimulates the synthesis of
      extracellular matrix proteins. The aim of work was the assessment of TGF-beta1
      concentration in children with renal polycystic disease. MATERIAL AND METHODS:
      The examined group (I) consisted of 33 children aged (median 14.7 years, range
      4.0-17.9): A--11 children with solitary cyst, B--22 with polycystic renal
      disease. Control group (C) consisted of 20 healthy children at the same age. The
      concentration of urinary TGF-b1 was measured using immunoenzymatic ELISA method.
      The results showed that mean concentration of urinary TGF-beta 1 (121.9 +/- 168
      pg/mg cr.) was lower than in group B, in which it was 207.2 +/- 361 pg/mg cr.
      However the difference was not statistically significant (p>0.05). In both
      subgroups (A and B) urinary excretion of TGF-beta1 was higher than in control
      group (C) (p<0.05). In 4 (36%) children from group A and 8 (36%) from group B the
      urinary concentration of TGF-beta 1 was below the sensitivity of the method. No
      correlation between TGF-beta 1 and children's age, urinary osmolality and GRF
      according to Schwartz was found. It was a positive correlation between urinary
      TGF-betal concentration and total diameter of renal cysts. CONCLUSIONS: TGF-betal
      takes part in renal cyst formation and increased urinary excretion of TGF-b1 in
      proportion to the dimension of renal cysts may be an evidence of that fact.

PMID- 16898502
TI  - [Target organ damage in children with newly diagnosed and untreated essential
      hypertension].
AB  - Target organ damage in the course of essential hypertension (EH) may develop
      already in childhood. The aim of the study was to determine the prevalence of
      left ventricular hypertrophy (LVH) and arterial damage and its main determinants
      in children with newly diagnosed, untreated EH. PATIENTS (pts): 87 children (22
      girls and 65 boys) with EH, age 14.4 +/- 3 (5-18) yrs. CONTROL GROUP: 104 healthy
      children (51 girls and 53 boys) aged 13.3 +/- 3.3 (5-20) yrs. STUDY DESIGN: cross
      sectional, controlled study. METHODS: evaluation of anthropometrical data, birth
      weight, family history towards cardiovascular diseases, serum biochemical
      cardiovascular risk factors (lipids, sCRP, homocysteine, uric acid), carotid
      (cIMT) and superficial femoral artery intima-media thickness (fIMT). In EH
      children ambulatory blood pressure monitoring (ABPM), echocardiography,
      ophthalmoscopy, microalbuminuria were evaluated. RESULTS: EH pts were
      significantly higher, heavier and had greater body mass index (BMI) (p<0.05). 59%
      of pts were overweight compared to 19% in control group (p<0.05). Carotid (cIMT)
      and superficial femoral artery intima-media thickness (fIMT) was greater in
      children with EH (0.47 +/- 0,05 v 0.43 +/- 0.04 and 0.36 +/- 0.04 v 0.33 +/-
      0.04) (p<0.05) respectively. 41% and 19% of pts had cIMT and fIMT above 2 SDS of
      normal values respectively. The prevalence of LVH was 45%, and in 12% of pts
      severe (left ventricular mass index--LVMi > 51 g/m2.7) LVH was diagnosed. Pts
      with LVH had higher birth weight than other pts 3525 < or = 598 v 3136 +/- 635 g
      (p=0.04) and LVMi correlated with higher birth weight (p=0.0001; r=0.358), 24
      hour heart rate (p=0.01; r= -0.361), serum uric acid (p=0.01; r=0.286),
      homocysteine (p=0.01; r=0.309) and apolipoprotein B (p=0.0001; r=0.258). LVMi
      correlated with fIMT (p=0.02; r=0.292), but not with cIMT. cIMT correlated with
      24-hour systolic blood pressure (SBP)(p=0.01; r=0.305), SBP load (p=0.01;
      r=0.377), puls pressure (PP) (p=0.01; r=0.292), and heart rate (HR) (p=0.01; r=
      0.285). 46% of pts had primary retinopathy, and 1 boy had secondary retinopathy.
      All pts had normal renal function, and mean microalbuminuria was 29.3+/-11.4
      mg/d. Positive family history towards EH was confirmed in 80% of pts vs 29% in
      controls (p<0.05). CONCLUSIONS: 1. Target organ damage is present already at the
      time of diagnosis in significant number of children with EH. 2. Overweight was
      59% of pts and only 19% of healthy children. 3. LVMi and markers of arterial
      injury correlate with SBP, PP and HR, fIMT, uric acid, homocysteine,
      apolipoprotein B and birth weight.

PMID- 16898503
TI  - [Oxidative stress and hypertensive arteriopathy in children with primary
      hypertension--preliminary results].
AB  - Hypertensive arteriopathy and intima-media (IMT) thickening is observed already
      in adolescents with primary hypertension (PH) at diagnosis. The injury of
      arterial wall may cause also generation of free radicals and free radicals may by
      itself perpetuate arterial wall injury. The aim of the study was to verify the
      hypothesis that children with PH are exposed to oxidative injury (Sox) due to
      impaired antioxidant barrier, and that markers of Sox correlate with IMT and
      metabolic risk factors of arteriosclerosis. STUDY DESIGN: controlled, cross
      sectional. PATIENTS: 76 children with untreated PH, aged 14.7 yrs (5-20): 23
      girls, 53 boys. CONTROLS: 83 healthy children aged 13.4 yrs (4-23): 44 girls, 39
      boys. METHODS: Sono-graphic assessment of IMT in common carotid (cIMT) and
      superficial femoral arteries (cIMT). Sox was assessed as thiobarbituric acid
      reactive substances plasma concentration (TBARS), glutathione plasma
      concentration (GSH) as well as, glutathione peroxidase activity (GPX) were tested
      to demonstrate free radical scavenger activity. RESULTS: PH pts had greater cIMT
      (p<0.0001), carotid wall cross sectional area (WCSA) (p<0.0001), fIMT (p<0.0001),
      lower HDL-cholesterol, apoA1/apoB than control group (p<0.05). GSH and GPX did
      not differ between groups but TBARS was significantly greater in PH pts (p
      <0.05). In control group fIMT significantly correlated with hCRP (r=0.30,
      p<0.01), homocysteine (r=0.3, p< 0.05), apoA1 (r=-0.2417, p<0.05), TBARS
      (r=0.329, p<0.01), GPX (r=-0.241, p<0.05) and with GSH (r=-0.22, p=0.05). In pts
      group, there were similar correlations between fIMT and hCRP (r=0.29, p<0.05),
      apoA1/apoB (r=-0.28, p<0.05). CONCLUSIONS: PH pts are exposed to significantly
      higher Sox than controls. The significant correlations between markers of Sox and
      biochemical parameters suggest that hypertensive arteriopathy is an effect of
      complex interplay between Sox, metabolic and hemodynamic insults.

PMID- 16898504
TI  - [Prehypertension risk factors in children and adolescents with type 1 diabetes].
AB  - AIM: Higher blood pressure is a marker of increased risk for development of
      diabetic angiopathy. The aim of the study was to evaluate the selected factors
      influencing the prevalence of prehypertension in T1DM children and adolescents.
      METHODOLOGY: 113 T1DM patients (62 male), aged 12-19 years, with diabetes
      duration from 0.5 to 17.3 years, without evidence of arterial hypertension during
      routine examination were recruited. In patients 24-hour automatic blood pressure
      (BP) monitoring was performed. Prehypertension was diagnosed SBP>120 mmHg and <
      95pc and/or DBP>80 mmHg and < 95pc. Among metabolic factors body mass index
      (BMI), lipids profile, HbA1c and insulin sensitivity index glucose disposal rate
      (euglycemic hiperinsulinemic clamp) were estimated. As an early marker of
      autonomic neuropathy heart rate variation was measured. RESULTS: None of the
      study patients had hypertension. In 35 individuals (31%) prehypertension was
      diagnosed. The prehypertension group had older age (17.4 vs. 15.8 years,
      p<0.001), longer duration of disease (6.6 vs. 4.3 years, p=0.003), greater BMI
      (23.8 vs. 22.0 kg/m2, p=0.01) and lower insulin sensitivity index (5.9 vs. 7.0
      mg/kg/min., p=0.04) as compared with the group with normal value of blood
      pressure. There were no differences between groups in lipids profile and HbA1c.
      In the patients with prehypertension the greater activity of sympathetic
      activation was observed (LF/HF--1. 0 vs. 0.82, p=0.02). CONCLUSIONS:
      Prehypertension is common feature in children and adolescents with type 1
      diabetes. The prevalence of prehypertension is associated with older age, longer
      duration of disease, greater BMI, lower insulin sensitivity and the shift of the
      sympathovagal balance toward sympathetic activation.

PMID- 16898505
TI  - [Birth weight and hypertension (HT) in children with reflux nephropathy (RN)].
AB  - Low birth weight (bw) has been related to low nephron number and hypertension.
      Age is an important predictor of developing hypertension in patients with reflux
      nephropathy (RN). The aim of the study was to assess the relationships between
      birth weight and blood pressure in children with RN. We investigated 150 patients
      in mean age 9 +/- 3.3 years with vesicoureteral reflux. In all patients we
      collected birth weight, we also performed renal scintigraphy (DMSA) and 24-hour
      ambulatory blood pressure monitoring (ABPM). Standard deviation score body mass
      index (BMI SDS) was calculated. In ABPM mean value of systolic and diastolic
      blood pressure (sBP, dBP), blood pressure load during 24 hour and during day and
      nighttime (LsBP, LdBP) were analyzed. As objective parameters of BP in children
      in different age and hight, systolic and diastolic BP indices (sBPI, dBPI) were
      calculated. RESULTS: In analyzed group of children mean bw was 3340 +/- 587 g
      (from 1300 to 5000 g); in 10 children bw was <2500 g. In 20 children (13%), in 3
      with bw <2500 g (30%) and in 17 (12.5%) with normal bw hypertension was
      diagnosed. The mean age and BMI SDS were lower in children with bw < 2500 g and
      HT than in children with normal bw and HT (8.2 vs 9.9 years and median -0.53 vs 
      0.22 respectively). In children with HT mean bw was 3247 +/- 666 g and in
      children without HT 3293 +/- 461 g (NS). No statistically significant difference
      was found depends of grades of renal damage in DMSA scan for bw. The negative
      correlation was found between bw and sBPI, LsBP during 24h and sBPI i LsBP during
      nighttime (p<0.05 r=-20, p<0.05 r=-19; p<0.05 r=-16, p<0.01 r=-26 respectively).
      No correlation was found between bw and dBP values. CONCLUSION: In children with
      RN low bw may be a potential risk factor for developing hypertension independent
      of severity of renal scarring.

PMID- 16898506
TI  - [Assessment of association of birth weight and existence of hypertension in
      children and adolescents normostenic, obese or with metabolic syndrome].
AB  - It has been proved that Low Birth Weight (LBW) is a predisposing factor of
      elevated blood pressure in children. The aim of our study was to analyze birth
      weight of patients with diagnosed hypertension (HT). There has been 114 children,
      6 to 17 years old, included into our study. We decided to divide them into 3
      following groups: Group I--normal body mass and HT (51 children); Group II-
      metabolic syndrome (MS) with HT (32 children); Group III--overweight and obese
      children with HT (31 children). At 85% of all patients HT was diagnosed after
      performing ABPM. Statistically significant difference of birth weight was
      observed between patients with normal body mass (I) and those with overweight or
      obesity (III) (p<0,01). The most number of children with LBW (<2500 g) was
      observed in Group I (15.7%) and Group II (12.5%). It was observed that obese
      children with HT had had normal or high birth weigh (96.8%). CONCLUSION: 1. The
      frequency of low birth weight is similar in normostenic children with
      hipertension and children with metabolic syndrome. 2. The birth weight higher
      than 4000 g is more frequent in obesy hipertensive children and children with
      metabolic syndrome than in normo-stenic patients with hipertension.

PMID- 16898507
TI  - [Serum TGF-beta1 level in children with reflux nephropathy].
AB  - Reflux nephropathy is a progressive renal scarring due to chronic pyelonephritis
      developing in patients with vesico-ureteral reflux. TGF-beta1 is thought to be
      one of the most important factor that initiates reflux nephropathy and stimulates
      its progression. The purpose of the study was to assess serum TGF-beta1 level in
      children with reflux nephropathy. The study comprised 36 children (12 boys and 24
      girls) aged 1-17 years with vesicoureteral reflux and renal scarring confirmed by
      scintigraphic evaluation. In most children recurrent urinary tract infections
      were observed. In 13 (27.8%) children, a first episode of urinary tract infection
      occurred in infancy. Primary vesico-ureteral reflux was diagnosed in 18 (50.0%)
      children. Secondary vesico-ureteral reflux due to anatomic or functional
      subvesical obstruction were recognized in 11 (30.6%) and 7 (19.4%) children,
      respectively. Serum TGF-beta1 levels were measured by ELISA. The mean serum TGF
      beta1 level in children with reflux nephropathy was significantly lower than that
      in controls (92.04 +/- 33.14 ng/ml vs 141.73 +/- 45.38 ng/ml). This might be a
      result of increased influx of serum TGF-beta1 into renal parenchyma and/or
      increased urinary TGF-beta1 excretion due to tubular damage in children with
      reflux nephropathy.

PMID- 16898508
TI  - [Prevalence of congenitial kidney and urinary tract anomalies in neonates and
      infants with congenital heart disease].
AB  - INTRODUCTION: Congenital heart diseases are the most frequent anomalies and one
      of the most important reasons of mortality and morbidity in neonates and infants.
      Coincidence of additional malformation aggravates prognosis. The frequency of
      incidence of other anomalies accompanying congenital hart diseases is defined as
      11 to 45%. AIM: Estimation of the frequency of a coincidence of congenital kidney
      anomalies on the basis of the ultrasound examination (US) in children with
      congenital heart disease in first year of life. MATERIAL AND METHODS: Abdominal
      US were done in 350 neonates and infants hospitalized in Department of Pediatric
      Cardiology Medical University of Gdansk in the first twenty-four hours after
      diagnosis of congenital heart disease. Examinations were performed in 187 male
      (53%) and 163 female (47%) in average age 54.9 days (range from 1 to 349 days).
      RESULTS: In examined population congenital kidney anomalies were found in 4.9% of
      children from which 18% represent hipoplasia, and another 18% dysplasia. 15.3% of
      examined patients were diagnosed by dilatation of collecting system, whereof 3%
      mild, 7% moderate, and 5% severe degree. CONCLUSIONS: 1. The frequency of
      incidence of kidney anomalies and collecting system dilatation in the examined
      population of neonates and infants with congenital heart disease accounts for
      20.2%. 2. Abdominal ultrasound screening with carefully examination of urinary
      tract should be performed in neonates and infants with congenital heart disease.

PMID- 16898509
TI  - [Vesicoureteral reflux in children with prenatal suspicion of urinary tract
      abnormalities].
AB  - AIM: The aim of the study was to assess indications to voiding cystourethrography
      (VCUG) in children with suspicion of urinary tract (UT) abnormalities in prenatal
      ultrasonography (US). MATERIAL AND METHODS: We studied 93 children aged 1 day to
      7 months (mean 1.4 +/- 1.3 months). Prenatal USG was done between 18-41 week of
      gestational age (mean 32.6 +/- 5.6). Congenital anomalies of UT were suspected in
      88% fetuses with dilatation of UT and in 12% fetuses with other changes in UT.
      Postnatal US was done in all children between 1-122 day of life (mean 18.2 +/-
      21.5); VCUG between 1 day to 13 months (mean 2.1 +/- 2.3 months), in this in 75
      (81%) infants in the first months of life. RESULTS: Abnormal result of postnatal
      US had 84 (90%) children (dilatation of pyelocalyceal system and/or ureter,
      duplex kidney, multicystic dysplastic kidney, ureterocele). We found normal VCUG
      in 67 (72%) children, abnormal in 26 (28%). Vesicoureteral reflux (VUR) to 28
      kidneys was detected in 20 (21.5%) children (1st--1 kidney, 2nd--14, 3rd--3, 4th-
      6 and 5th--4 kidneys); another anomalies in 6 (in 2 posterior urethral valves).
      VUR was observed in 17.3% VCUG performed before 3 months of age and in 38.9%
      performed later (p<0.05). VUR was recognized: in 17.2% kidneys with normal
      prenatal US and in 16.4% kidneys with dilatation of UT (NS); in 6 (8%) kidneys
      with normal postnatal US and 22 (29.8%) with abnormal (p=0.05). There was not
      statistically significant difference in frequency of VUR in kidney with normal (0
      5 mm) and abnormal postnatal renal pelvic diameter (RPD) (11.3% vs 19%, NS). The
      sensivity and specifity of normal postnatal USG in detection VUR were 79% and 56%
      respectively, and of normal postnatal RPD were 61% and 46% respectively.
      CONCLUSIONS: 1. Indication to performing VCUG in children with prenatally
      detected hydronephrosis should be persistent dilatation of pyelocalyceal system
      and/or ureter in postnatal US or another abnormalities in UT. 2. Normal prenatal
      and postnatal USG does not exclude presence of VUR. 3. VCUG in children with
      prenatally detected hydronephrosis should be performed about 3 months of life, in
      specially situation earlier.

PMID- 16898510
TI  - [Ultrasound imaging of stones dislocation in urinary tract after lithotripsy
      treatment in children with urolithiasis].
AB  - The aim of the study was to establish the usefulness of ultrasound examination
      for imaging of stones dislocation in urinary tract after lithotripsy treatment.
      The study group included 335 children with urolithiasis treated in our Clinic
      since 1994 until 2005y. In the group were 295 (88%) children with nephrolithiasis
      and 40 (12%) children with ureterolithiasis. In the whole group 335 children
      there were performed 619 lithotripsy procedures--545 kidney and 74 ureter units.
      The ultrasound examinations were performed in each patient before, on the first
      and second day of the treatment and two months after using the Hitachi EUB 315
      with 5Mhz transducer. In the ultrasound examinations after lithotripsy treatment:
      in 596/619 (96,3%) cases imaging of stones dislocation in urinary tract and
      urinary retention was possible.

PMID- 16898512
TI  - [Megacalycosis as a diagnostic problem in children].
AB  - Megacalycosis is an uncommon, congenital renal abnormality, characterized by
      nonobstructive dilatation of the renal calyces with normal renal pelvis, ureter
      and bladder. This condition is due to underdevelopement or hypoplasia of
      Malpighie's pyramids. It usually occurs unilateraly as the isolated anomaly with
      strong male predominance. Megacalycosis itself does not impair the renal function
      but it can be the cause of urinary tract infections and calculus formation. This
      congenital defect is incidentally found by urography during the examination for
      urolithiasis or urinary tract infections or calculus formation. The images on
      radograms can be confused with obstructive or refluxing hydronephrosis or
      postinflamtory changes typical for pyelonephritis chronica. In case of
      megacalycosis surgical treatment is unnecessary. Patients with this condition
      should be followed-up with ultrasound and prevention of urinary tract infections
      or urolithiasis. Here we would like to report on the case of megacalycosis in a
      ten-year-old girl reffered to our deprtament due to UTI. Diagnosis of
      megacalycosis was established by typical urography findings: dilatation of renal
      calyces, no distention or obstruction of renal pelvic and ureter. The renal
      function was normal. No evidence of abnormality in cystoureterogram and
      uroflowmetry test was detected.

PMID- 16898511
TI  - [Urinary citrate excretion in children with calcium urolithiasis].
AB  - Citrate is thought to be one of the most important inhibitor of calcium salts
      crystallization in the urine. Therefore, an assessment of urinary citrate
      excretion is an integral element of metabolic evaluation in urolithiasis. The
      reported incidence of urolithiasis associated with hypocitraturia varies from 10%
      to 63%. The purpose of the study was to assess urinary citrate excretion in
      children with calcium urolithiasis living in region of Lublin. The study
      comprised 60 children (34 boys and 26 girls) aged 4.3-18 years. In 36 of them,
      calcium oxalate urolithiasis was diagnosed by spectrophotometry. In the remaining
      children, an assessment of stone composition was impossible. However, in all
      children, stones were radiopaque. Hypercalciuria (HC) and mild hyperoxaluria
      (HOx) were diagnosed in 23 and 16 children, respectively. In the remaining 21
      children urolihiasis was classified as idiopathic. The controls were 35 healthy
      age- and gender-matched children. Urinary citrate excretions were assessed by
      enzymatic method in 24-hour urine specimens and expressed as citrate/creatinine
      ratios (Cit/Cr). Decreased Cit/Cr were observed in 9 (15%) children with calcium
      urolithiasis. However, there was no significant difference between the mean Cit/
      Cr in children with calcium urolithiasis and controls (410 +/- 207 mg/g vs 385 +/
      144 mg/g). There was also no significant difference between the mean Cit/ Cr in
      children with HC and controls. Similarly, the mean Cit/Cr did not differ
      significantly between children with HOx and controls. However, the lowest mean
      Cit/Cr was revealed in children with HOx (306 +/- 161 mg/g). CONCLUSIONS: In most
      children with calcium urolithiasis urinary citrate excretion was normal. However,
      in some children with urolithiasis, detection of hypocitraturia allows to explain
      pathogenesis of stone formation and to carry on a causative prophylaxis.

PMID- 16898513
TI  - [New, successful treatment of urinary tract infection caused by Pseudomonas
      aeruginosa].
AB  - Urinary tract infection (UTI) is common in pediatric practice and an important
      cause of morbidity and mortality in children. Escherichia coli remains the
      predominant uropathogen (80%) isolated in acute community-acquired uncomplicated
      infections, followed by Staphylococcus saprophyticus (10% to 15%) and Pseudomonas
      aeruginosa (9%) The pathogens traditionally associated with UTI are changing many
      of their features, particularly because of antimicrobial resistance. Reinfections
      and relapses of urinary tract infections caused by PA are very frequent. The aim
      of the study was to evaluate the efficacy of combined clarithromycine and
      ceftazidime in terms of eradication of PA infection. We analyzed 20 out of 264
      children with UTI where PA infection was confirmed with urine culture. Those
      children were treated for at least 14 days with the protocol used for PA
      infection in patients with mucoviscidosis. Short-term eradication was achieved in
      all patients. Long-term study revealed relapse in 25% of children, all with
      serious congenital malformations. 75% of children were treated with success. No
      side effects were observed. Conclusion. We conclude that an empirical combination
      treatment of clarithromycine and ceftazidime is appropriate and effective in
      children with UTI caused by PA. This therapy was clinically efficacious, well
      tolerated, and cost effective, and should prevent unnecessary development of
      antimicrobial resistance.

PMID- 16898514
TI  - [Voiding dysfunction in children with vesicoureteral reflux].
AB  - The aim of the study was to assess the rate of development of voiding dysfunction
      (VD) in patients with reflux nephropathy. We investigated 150 pts with
      vesicoureteral reflux (VUR): 33 boys and 117 girls in mean age 9 +/- 3.3 years
      with normal renal function. In all pts we performed renal scintigraphy (DMSA) and
      ABPM. Renal scarring by DMSA scan was categorized into grades 1-4. In all pts we
      assessed high and laterality of VUR, renal function (clearance creatinine--Ccr)
      and occurency of hypertension (HT). RESULTS: Of 150 pts, 80 (53.3%) developed VD
      (54.5% boys and 52% girls). DMSA grade: 1--27 pts, 2--85 pts; 3--31 pts; 4--7
      pts. No statistically significant difference was found depends of: sex, age,
      laterality of renal damage in DMSA, unilateral and bilateral reflux for the
      development of VD. The incidence 3-4 grade in DMSA scan was significantly higher
      in pts with IV-V grade of VUR in comparison to pts with lower grade of VUR in
      group with and without voiding dysfunction. IV-V grades of VUR were observed more
      frequently in pts with bladder/sphincter dysfunction. The occurency of HT in
      group with VD and without VD was 12 pts (15%) and 8 (11.4%) respectively (ns).
      Pts with VD have lower Ccr in comparison with pts without VD (129.1 vs 136.3
      ml/min/1.73 m2; p<0.05). CONCLUSIONS: Approximately 50% of patients with VUR
      demonstrated VD. VD occurred independent of age. IV-V degrees VUR and more severe
      changes in DMSA scan were seen in pts with bladder/sphincter dysfunction.

PMID- 16898515
TI  - [Chronic renal disease in boys with posterior urethral valve].
AB  - Posterior urethral valve (PUV) is the most common anatomical cause of bladder
      outlet obstruction with an incidence ranging from 1/3000 to 1/8000 births. In
      spite of early valve ablation deterioration of renal function is frequently
      reported during childhood and adolescence. AIM OF THE STUDY: To evaluate the
      frequency and progression of chronic renal disease in boys born with PUV.
      MATERIALS AND METHODS: The presence of chronic renal disease (CRD) in 58 boys
      with posterior urethral valve (PUV) was assessed by renal ultrasound and
      estimation of glomerular filtration rate (GFR). GFR was estimated by the method
      of Schwartz. Chronic renal disease was defined according to NFK K/DOQI Guidelines
      and classified into 5 stages. RESULTS: 48 (82%) patients with PUV had CRD. Among
      the patients observed from birth 89% already demonstrated CRD in the first year
      of life. CONCLUSIONS: 1. The vast majority of boys with PUV (83%) demonstrate
      symptoms of chronic renal disease. 2. CRD in boys with PUV is frequently evident
      from the first year of life. 3. PUV patients require regular nephrologic
      assessment from birth.

PMID- 16898516
TI  - [Diagnostic value of PTH total kit for estimation of bone turnover in children
      with chronic renal failure].
AB  - The aim of the study was to estimate the usefulness of total PTH and 1-84
      molecule (CAP) assay in clinical practice. 118 children with chronic renal
      failure aged 13.8 +/- 4.5 years were examined: 69 on conservative treatment with
      creatinine clearance 40.7 +/- 20 ml/min/1.73 m2, 31 on peritoneal dialysis and 16
      on hemodialysis. In all patients the following parameters were assessed: serum
      levels of calcium (sCa), phosphorus (sP), PTH intact (PTHs) by chemiluminescence
      method (Immulite analyzer), total PTH (PTHc) and CAP with Duo PTH Assay
      (Scantibodies Laboratories, USA). The value of CIP as the difference between
      total PTH and CAP was calculated. For the evaluation of bone turnover the serum
      level of osteocalcin (OC) with IRMA, (OsteoRiact, CIS, F) and activity of serum
      alkaline phosphatase (AP) were determined. The correlations between parameters
      were calculated by Pearson's correlation coefficient (r). RESULTS: Significant
      correlation were found between PTHs and PTHc (r=0.84, p=0.0000), CAP (r=0.79,
      p=0.0000) and CIP. The increase of PTHs, PTHc, CAP, CIP, sP, OC and percentage of
      CIP were noticed, when parallel increase of creatinine level was found. The
      negative correlation between creatinine level and CAP/CIP was observed. The
      similar correlations between level of PTHs, PTHc, CAP and OC level were observed
      (r=0.55, 0.49 and 0.50 respectively). CONCLUSION: The assay of total PTH and CAP
      fragment is not usefull in clinical practice for estimation of bone turnover in
      children with chronic renal failure.

PMID- 16898517
TI  - [The causes of the end of growth hormone treatment in children with chronic renal
      failure].
AB  - Growth deficiency is one of complications in chronic renal failure (CRF). In
      Poland recombinant human growth hormone (rhGH) was introduce to treatment in
      children with CRF in 1994. The aim of study was to evaluate causes of the end of
      rhGH treatment in children with CRF. PATIENTS AND METHODS: Among 90 children with
      different stages of CRF treated with rhGH between 2000-2005 we analyzed 85
      patients (33 in CRF and 52 in ESRD), in mean age 9.8 years (from 3 to 17.8 years)
      which finished therapy. RhGH was used subcutaneously, everyday in doses 1.1
      j/kg/week. The anthropometric measurements were performed at the beginning and
      after one year of the study. RESULTS: The mean time of treatment in 85 children
      was 18.4 months (1-60 months). The causes of the treatment termination were:
      renal transplantation in 40 pts (47%), increase of PTH serum level in 13 pts
      (15.3%), lack of treatment effect in 10pts (11.8%), height achievement at the
      level of 10c in 10 pts (11.8%), non compliance in 3 pts (3.5%), patient's
      decision of finishing therapy in 6 pts (7%) and the diagnosis of diabetes during
      rhGH treatment in 1 pts (1.2%), acute pancreatitis in 1pts (1.2%), epilepsy in 1
      pts (1.2%). 25 (29.5%) of out 85 analyzed children had finished the study in the
      first year. In other 60 patients mean growth velocity was 8.1 cm/year (from 3.3
      to 12.4 cm/year). CONCLUSIONS: The main causes of the termination of rhGH
      treatment in children with CRF were renal transplantation and decompensated
      secondary hyperparathyroidism.

PMID- 16898518
TI  - [Calpain-calpastatin system in erythrocytes of children with chronic renal
      failure].
AB  - INTRODUCTION: Disturbances of erythrocyte calcium homeostasis in the course of
      chronic renal failure (CRF) may result from impaired function of a membrane
      calcium pump (PMCA). Plasma membrane Ca+2-transport ATP-ase is responsible for
      maintaining cytoplasmic level of intracellular Ca+2. PMCA activity is regulated
      by high Ca levels and calmodulin, in case of Ca+2 deficiency--by intracellular
      cysteine protease--calpain, and its natural inhibitor--calpastatin. The aim of
      the study was to assess the relationship between the activity of PMCA and calpain
      calpastatin system in erythrocytes of children with CRF treated conservatively.
      MATERIAL AND METHODS: The study was performed on 21 CRF children treated
      conservatively (gr. I) aged 6-18 years. The control group consisted of 18 healthy
      age matched children. The parameters evaluated in erythrocytes were as follows:
      calpain-calpastatin system (Cp-Cs) activity, PMCA activity, level of
      intracellular Ca (Cai+2) and calmodulin (Ca) activity. RESULTS: Our investigation
      revealed: calmodulin concentrations decrement in CRF children (2.08 +/- 0.51
      mg/L) vs. controls (4.54 +/- 1.09 nmol/min/mg) (p<0.01), calpain activity in CRF
      children (60.56 +/- 12.43 U/mg) higher than in controls (45.34 +/- 5.65 U/mg)
      (p<0.01) and calpastatin activity increment in gr. I (40.03 +/- 10.24 U/mg) vs.
      control group (20.123.05 U/mg) (p<0.01). Decreased activity of a system
      containing an enzyme and its inhibitor (calpain-calpastatin) was also observed: 1
      : 0.66 ratio in gr. I vs 1:0.4 ratio in controls. CONCLUSIONS: There is a
      decrease inPMCA activity and an increase of intracellular calcium in erythrocytes
      of children with mild CRF. The concomitant increment of erythrocyte calpastatin
      is the cause of disturbances in calpain-calpastatin system, thus unabling
      normalization of PMCA pump activity.

PMID- 16898519
TI  - [Blood and urine endothelin and nitric oxide levels in predialysis children with
      chronic renal failure].
AB  - Endothelial dysfunction was observed in patients with chronic renal failure
      (CRF). Endothelial cells produce a lot of factors among them endothelin and
      nitric oxide. The aim of this study was to evaluate the plasma/serum and urine
      levels of edothelin 1 (ET 1) and nitric oxide (NO) in children with CRF treated
      conservatively. 52 children (23 girls and 29 boys) aged 2-20 years (mean 13.19
      years) were enrolled into the study. Patients were divided into 2 groups
      according to the creatinine level: group I--children with CRF and creatinine
      level below 265.2 micromol/l, group II CRF children with creatinine level above
      265.2 micromol/l. We evaluated serum and urine metabolites of NO (nitrates +
      nitrites). IN CONCLUSION: in children with chronic renal failure elevated level
      of ET1 and enhanced excretion of ET1 were observed. Decreased plasma and urine
      NOx levels were found in CRF children. The disorders are connected with
      progression of renal failure.

PMID- 16898520
TI  - [Ten-year experience in renal replacement therapy in children. A report from
      Dialysis Center, Department of Pediatric Nephrology, Children's University
      Hospital in Lublin].
AB  - Since January 26th of 1996, when our center was established, 34 children (19 boys
      and 15 girls) with end-stage renal disease (ESRD) were treated with renal
      replacement therapy. Maintenance hemodialysis (HD) and peritoneal dialysis (PO)
      were received by 28 and 6 patients, respectively. In our patients, the most
      common cause of ESRD were congenital urinary system malformations (61.7%) and
      glomerulonephritides (20.6%). Duration of renal replace-ment therapy varied from
      6 months to 8 years. In 71.5% of children on HD, vascular access was established
      by arteriovenous fistula, and in the remaining--by permanent venous catheter.
      Adequacy of renal replacement therapy was estimated by Kt/V ratio. In patients on
      HD and PO, Kt/V ratios were 1.27 and 1.9 per 7 days, respectively. In 82.4% of
      patients, pre-dialysis arterial hypertension was observed. During renal
      replacement therapy arterial hypertension was diagnosed in 73.5% of children.
      Anemia resulting from ESRD was treated with recombinant human erythropoietin and
      erythropoietic medicines. In all children, recommended hemoglobin and hematocrit
      levels were achieved. In our patients, parameters of calcium and phosphate
      handling were also monitored. The mean serum intact parathormone levels in HD and
      PO children were 304 pg/ml and 302.2 pg/ml, respectively. We also summarized the
      occurrence of hepatotropic viral infections and endocrine disturbances including
      hypothyreosis and short stature in our patients. 3 children died due to ESRD
      complication. 22 (64,7%) children received cadaver-donor renal transplants.

PMID- 16898521
TI  - [Are permanent catheters a safe vascular access in chronically hemodialysed
      children?].
AB  - The paper's aim is an analysis of the complications related to permanent
      catheters used as a vascular access in chronically hemodialysed (HD) children.
      From 1998 to 2005. 34 surgically implanted permanent catheters were used as a
      vascular access for HD in 21 patients at average age of 13,6 (range 5-26) yrs.
      The catheters were placed mainly into right internal jugular vein or less often
      into left i.j.v., left subclavian v. and femoral veins. In 12 patients only one
      catheter was used for HD, in the others--the catheters had to be replaced. The
      average patient's observation period was 17 (range 3-73) months and the average
      catheter's usage period was 10,6 (range 0.5-40) months. In 9 children the
      catheter function period was shorter than 12 months. No complications were
      observed only in 2 patients with short observation's period (< 6 months). The
      complication frequency rate amounted to 0,7 epizode/observation month (range 0.0
      5.0), the thrombotic complications rate was 0,3 and the infectious complications
      index was 0.2 episode/month, respectively. The rare mechanical dysfunctions were
      noted in 2 patients (the catheter's rupture and falling out). The serious
      thrombotic complications were noted in 2 cases (carotic veins bilateral severe
      stenosis with marked collateral circulation accompanied and extensive thrombosis
      of the femoral and iliac veins). The diagnostic and therapeutic angio-graphic
      investigation of carotic venous system and catheter placement were performed in 2
      patients. The Urokinase was used in 13 children (repeatedly in 8 HD subjects). In
      the follow up, among 34 analyzed catheters--the function of 11 (32%) was
      appropriate, 13 (38%) were exchanged, 6 (18%)--surgically replaced, in 6 cases
      the catheters were removed with subsequent changing the vascular access or
      dialysis modatlity (in 1 case on patient's demand). CONCLUSIONS: The use of
      permanent catheter as a chronic vascular access for HD in children is associated
      with high rate of complications. However, this type of vascular access should be
      considered as a last resort when creation of the other vascular access is
      unlikely.

PMID- 16898522
TI  - [Percutaneus endoscopic gastrostomy (PEG) in an infant with chronic renal
      failure].
AB  - Malnutrition is a major problem in patients with chronic renal failure,
      especially in children in the first three years of life. Meeting high energy
      needs in these patients may be difficult because of anorexia and vomiting, which
      are common in predialysis renal failure. Nutritional support for children with
      chronic renal failure often involves the use of nasogastric tubes or gastrostomy
      feeding. We describe an infant with pre-dialysis renal failure and severe
      malnutrition in whom only insertion of percutaneus endoscopic gastrostomy
      provided adequate caloric intake and satisfactory weight gain.

PMID- 16898523
TI  - [A child with myelomeningocele as a dialytic patient].
AB  - The aim of the study was to present difficulties and problems of dialytic
      treatment in children with spina bifida (SB). Between 2000 and 2005 five girls
      with SB and neurogenic bladder were treated with renal replacement therapy (15%
      of all children with end stage kidney disease dialyzed at our centre). Four
      patients (pts) had hydrocephalus requiring ventriculoperitoneal shunt, they were
      wheelchair-bound due to lower limbs paralysis and mentally retarded. Only 1 girl
      had been supervised by nephrologist from the very beginning. Dialysis was started
      at the age of 3-17 yr and the first mode was automatic peritoneal dialysis (ADO)
      in 3 and hemodialysis (HD) in 2. During the treatment ADO was switched onto HD in
      2 pts for sclerosing encapsulating peritonitis (1) and tunnel infection with
      spontaneous Tenckhoff catheter evacuation (1). Permanent central venous catheters
      served as vascular access in 3 cases, in 2 there were difficulties with creation
      of arteriovenous fistula. No neurological complications were noticed in pts with
      ventriculo-peritoneal shunt and ADO. Total period of renal replacement therapy
      was 9-99 mo. Only 2 pts were qualified to transplantation. Two pts died after 16
      mo of dialysis, 2 were transplanted and 1 is still being treated with HD. All
      families were dysfunctional. In 4 cases insufficient parental support caused many
      disturbances during predialytic and dialytic period. We concluded that in Poland
      pediatric pts with SB create specific group with the number of problems and
      complications higher than in other children on dialysis.

PMID- 16898524
TI  - [Apoptosis in patients with chronic renal failure (CRF)].
AB  - Apoptosis is a programmed active and selective mechanisms of cell death allowing
      for the removal of cells in the living organisms. It is initiated by a number of
      stimuli, which are subject to complicated regulating system. It is proved that
      apoptosis plays a significant role in immunological disorders in uremic patients.
      The aim of the study was to estimate activity of apoptosis in peripheral blood
      mononuclear cells of patients with chronic renal failure treated in our
      Department. MATERIAL AND METHODS: 70 patients (13 on HD, 14 on PD and 24 pre
      dialysis uremic children) were enrolled in the study. The control group comprised
      19 children. We evaluated activity of mononuclear cells apoptosis exposed to
      Annexin V-FITC, Fas Ligand and Bcl-2 proteins activity were investigated also.
      RESULTS: The results show that cell apoptosis was increased in pre-dialysis
      uremic patients (both phases early and late). The activity of Fas Ligand protein
      was similar in every group and activity of Bcl-2 protein was significant higher
      in HD and PD patients. CONCLUSIONS: The highest intensity of mononuclear cell
      apoptosis in pre-dialysis children was observed. The significantly enhanced
      activity of Bcl-2 protein in dialysis patients probably protected from apoptosis.

PMID- 16898525
TI  - [Evaluation of pharmacokinetics and safety of valganciclovir oral suspension
      treatment in pediatric kidney graft recipients--preliminary report].
AB  - BACKGROUND: Invasive CMV disease in transplanted organ recipients is a life
      threatening condition. CMV infection is also known risk factor for acute
      rejection and chronic allograft nephropathy. The risk of CMV infection in
      pediatric population is high, especially in terms of primary infection. It can be
      significantly reduced under long term (3 months) prophylaxis with ganciclovir
      (GCV), available exclusively as parenteral drug. Since recently oral tablet pro
      drug valganciclovir (VCV, Valcyte, Roche) is given in adult patients. This drug
      has proved similar efficacy and good bioavailability (roughly 70%), however there
      is no registered liquid form which can be precisely and safety administered in
      small children. MATERIAL AND METHOD: 10 children after kidney transplantation,
      aged 2-9.5 year (mean 5.1; SD +/- 2.3), body weight 8.5-19.5 kg (mean 14.6; SD +/
      3.5), with good graft function (serum creatinine 0.3-0.8 mg/dl) were given VCV
      oral suspension prepared in hospital pharmacy, using Valcyte tablets and
      commercially available vehicle (Paddock Laboratories, Inc) (60 mg/ml), 7.5 mg/kg
      b.w., 2-3 x/day. Through level (CO) of GCV in blood was measured in all patient,
      in 4 patient drug kinetics (4 measurements) was also analyzed preceded with
      evaluation of GCV elimination after intravenous infusion of GCV. RESULTS: There
      was no episode of drug toxicity nor drug withdrawal from other reason. CO (mean =
      0.74 microg/ml; max. 1.15; min. 0.38; SD +/- 0.25) was close to predefined values
      (0.4-1.0 microg/ml). Concentration profile of GCV (Cmax 1.0-1.5 h post dose) was
      similar to profile observed in adult patient treated with VCG tablets.
      CONCLUSION: Treatment with VCV suspension provides precise dosage and seems to be
      safe in patient with low body weight. It enables ambulatory prophylaxis and
      treatment of CMV infection.

PMID- 16898527
TI  - [Polish nurses attitude toward organ transplatation].
AB  - The aim of the study was to analyze basic knowledge and attitude toward organs
      transplantation (Tx) among nurses working in Polish hospitals. The original
      questionnaire was sent to 269 nurses and 246 answers were received: 122 from
      dialysis and/or transplantation units (group I) and 124 from other departments
      (group II). Knowledge, estimated with a ten-questions test, was higher in group I
      and also depended on sex, educational status, period of working and place of
      live. Nurses having in family a person waiting for Tx achieved better results in
      the test than others. 86.2% of responders agree to serve as a donor after death
      (group I--86.1%, group II--86.3%), 89.0% (86.1% vs 91.9%; p>0.05)--to be treated
      with cadaveric donor Tx and 80.9% (71.3% vs 90.3%; p<0.05)--with living related
      donor (LRD) kidney Tx. 98.0% (97.5% vs 98.4%) want to give the kidney for family
      Tx if they are asked to. 9.3% (4.1% vs 14.5%, p>0.05) claim that some form of
      financial support for living donors is justified. 74,4% (84.4% vs 64.5%, p>0.05)
      have talked with the family about Tx and 65,0% (77.0% vs 53.2%; p>0.05)
      transferred their opinion about organs donation. 40% of nurses who haven't agreed
      for organ donation after death want to be treated with Tx. The main sources of
      knowledge about Tx are medical publications (62.6%) and media (40.6%). Our study
      indicates, that nurses present positive attitude toward organ donation and
      reception independently of the place of work (dialysis/transplantation or other
      department). LRD kidney donation is the most accepted transplantational
      procedure.

PMID- 16898526
TI  - [Bilateral papillary renal cell carcinoma in a patient post-renal
      transplantation].
AB  - Renal cancer accounts for about 2% of all cancers in general population. One of
      the risk factors is acquired cystic kidney disease developed in course of end-
      stage renal failure. About 2% of cases of renal cancer are associated with
      inherited syndromes. We present here the case of 18-year old boy with papillary
      bilateral renal cell carcinoma, which was found 3 years after renal
      transplantation, in the stage of graft failure, few days after graphtectomy,
      while looking for the reason of persistent fever.

PMID- 16898528
TI  - [Does daily hemodialysis influence urea kinetic modeling (UKM) coefficients?-
      Preliminary report].
AB  - Large number of data shows beneficial effects of implementing daily hemodialysis
      (DH) upon the outcome in patients dialysed previously in 3 times a week
      hemodialysis (3H) schedule. The mechanisms responsible for this phenomenon are
      still unclear, despite the time of low-flux DH sessions is shortened almost by
      half. Evaluation of the effect of doubling the number of hemodialyses per week
      upon so called cellular clearance (intercompartmental diffusion coefficient, Kc)
      computed in 2 pool-model was main aim of this study. 6 chronically dialysed
      patients (previously 3x per week) were subjected to DH. Based upon output data
      from UKM and weekly KT/V, the time for each DH session was computed, with no
      change in Kd (dialyser clearance). Kc was estimated from double-pool volume
      variable model equations and rebound. By the use of almost similar dialyser
      clearances in 16 conventional and 29 DH modeling sessions, estimated Kc values
      had been found non significantly higher in DH: (323.16; S.D. 187.86 vs. 268.80;
      S.D. 104.09 ml/min; p=0,68). Mean ultrafiltration/pre-dialysis body weight ratio
      (UFR/BW1) was 4,97 (S.D. 2.27)% in conventional hemodialysis and 3.66 (S.D.
      1.46)% in DH. Mean dialysis index Kt/V values had decreased in DH (0.79; S.D.
      0.17, vs. 1,34 (S.D. 0.26). Mean UFR/W1 ratio correlated negatively with Kc
      either in conventional or in DH (r=-0.653; p = 0.006 and r=-0.552; p=0.0036,
      respectively). Statistically significant negative correlation between Kt/V and Kc
      was found only in DH subjects (r=-0.466, p =0.010). The authors concluded, that
      increased Kc observed in patients subjected to DH may be responsible for better
      dialysis efficacy in patients switched into this treatment modality.

PMID- 16898529
TI  - [Interleukin-17 concentration in serum and urine of children with idiopathic
      nephrotic syndrome].
AB  - T-cells and their cytokines play an important role in the pathogenesis of
      idiopathic nephrotic syndrome (INS) in children. IL-17 secreted by activated CD4+
      Tcells induces production of proinflammatory mediators, enhances T-cell-mediated
      immune responses and Th1 type reactions. The aim of the study was to evaluate IL
      17 concentrations in serum and urine of children with INS and determine the
      possible role of this cytokine in the course of disease. PATIENTS AND METHODS: 67
      children with INS, aged 3 to 16 years (mean 9 +/- 4) and 15 normal controls were
      included in the study. The patients were divided into 2 groups according to
      activity of the disease: I (n=37)--INS in relapse, II (n=30)--INS in remission.
      Serum (s) and urinary (u) IL-17 were determined by immunoenzymatic method. In
      children with INS serum biochemical parameters, clearance of endogene creatinine
      and 24 hour proteinuria were measured. RESULTS: sIL-17 and uIL-17 concentrations
      (51.66 +/- 8.38 pg/mg and 56.29 +/-14.24 pg/mg creatinine (cr), respectively)
      were significantly higher (p<0.001) in group I compared with group II (35.7 +/-
      10.18 pg/ml and 17.47 +/- 3.46 pg/mg cr) and normal controls (27.17 +/- 1.87
      pg/ml and 13.91 +/- 1.22 pg/mg cr). UIL-17 correlated positively with sIL-17
      (r=0.783, p<0.0001). A positive correlations between uIL-17 and sIL-17 and
      urinary protein excretion were found (r=0.58, r=0.42, respectively; p<0.05). IN
      CONCLUSION: elevated serum and urinary IL-17 levels in children with relapse of
      nephrotic syndrome suggest the role of IL-17 in the pathophysiology of INS. IL-17
      concentrations in serum and urine may reflect the disease activity of INS.

PMID- 16898530
TI  - [Lipids abnormalities in children with refractory nephrotic proteinuria].
AB  - The aim of the study is to evaluate the lipids disorders in children with
      refractory proteinuria in acute phase and remission of the disease. The study
      group consist of 39 children, mean age 8.2 +/- 3.9 years with refractory
      nephrotic syndrome (RNS)/nephrotic proteinuria (RNP), wchich were divided in 3
      groups according to RNS/RNP frequency: group A--17 children up to 3 times, group
      B--13 children 4-9 times, group C--9 children > or = 10 times. Total number of
      relapses was 53. In all children at the start and every 3 months, the total
      cholesterol concentration (TC), LDL, HDL cholesterol, triglicerydes (TG),
      apolipoprotein A1(apoA1), apoliporotein B100 (apoB100 ) were measured. The
      duration of the study was 12 months. RESULTS: Children with NS/NP in the acute
      phase of the disease show high levels of TC, TG, LDL-C and apolipoproteins: apo
      AI, apo B100, The level of HDL-C was normal. In the groups A, B, C a
      normalization of average levels of apo B100, was recorded after 3 month, apo AI
      after 3 to 6 months. With the increasing amount of relapses the time to
      normalization of average levels of TC and LDL-C was prolonged. Normal average
      levels of LDL-C were recorded in the group A after 3 months, in the group B after
      9 months, in the group C was still high. TC normalization was recorded after 6
      months only in the group A, in the groups B and C the level was high; TG was high
      during 12 months of observation in all groups. CONCLUSION: The persistance of
      high TC, LDL-C and TG levels during the remission phase in children with higher
      numbers of NS/NP relapses is a risk factor of atherosclerosis developement.

PMID- 16898531
TI  - [Evaluation of arterial intima-media thickness (IMT) in children with idiopathic
      nephrotic syndrome--preliminary report].
AB  - One the complications of idiopathic nephrotic syndrome (i.n.s.) is long-lasting
      lipid unfavourable lipid profile, a risk factor of early atherosclerosis. Aim of
      the study was evaluation of the incidence of early signs of atheromathosis in
      children with INS expressed as the increased IMT in the (elastic) common carotid
      (cIMT) and (muscular) superficial femoral ((fIMT) arteries. The study included 50
      children (34 boys and 16 girls) aged from 5.83 to 16.58 y (mean 10,8) with INS
      Overall duration of the disease ranged from 2.58 to 13.83 y (mean 7.81) [in 23
      (46%) children < 10 yrs mean 6.21 yrs; in 16 (32%) from 10 to 14 yrs mean 11.93
      yrs and in 11 (22%) >14 yrs mean 4.27 yrs]. 16 children were treated with
      prednisone, 32 with cyclosporine A (CsA) and 2 mycophenolate mofetil (MMF). The
      renal function in 49 children was normal and decreased in 1 case. Children
      treated with CsA and MMF received renoprotection with enalapril or
      enalapril/losartan. USG technique was used to evaluate cIMT and fIMT. In 39 (78%)
      pts, 26/34 (76.47%) > and 13/16 (81.25%) + cIMT was increased. fIMT was increased
      in 13 (26%) pts, including 12/34 (35.29%) > and 1/16 (6.25%) +. Among pts <10y.
      of age cIMT was increased in 19/23 (82.6%) and fIMT in 5/23 (21.73%). Among pts
      between 10-14 yrs cIMT was increased in 13/16 (81.25%), and fIMT in 4/16 (25%).
      Among pts >14 yrs cIMT was increased in 7/11 (63.63%), and fIMT in 4 (36,36%)
      cases. CONCLUSION: Increased intima-media thickness in (elastic) carotid artery
      was shown in vast majority of children with nephrotic syndrome.

PMID- 16898533
TI  - [Incidence of urinary system malformations in children with the nephrotic
      syndrome].
AB  - The purposes of the study were a) to assess the incidence of urinary system
      malformations in children with the nephrotic syndrome (NS) and b) to estimate
      their effect on clinical course of the NS. A retrospective analysis comprised
      medical records of patients aged 2-18 years hospitalized in the Department of
      Pediatric Nephrology, University Children's Hospital, Lublin. Urinary tract
      infections (UTI) occurred in 28% of children with the NS. Imaging evaluation
      revealed urinary system malformations in 21.2% of children with the NS and UTI.
      Urinary system malformations constituted 5.9% of all children hospitalized
      because of the NS. Urinary system malformations included vesico-ureteral reflux
      (42.8%), renal duplication (28.6%), renal agenesis (14.3%) and diverticulum of
      the bladder (14.3%). In 48% of children with the NS and urinary system
      malformations, frequent recurrences of the syndrome were observed.

PMID- 16898532
TI  - [Expression of zeta (zeta) chain in peripheral blood T lymphocytes and NK cells
      of children with idiopathic nephrotic syndrome (INS)--preliminary results].
AB  - Cellular immune disturbances have been implicated in the pathogenesis of
      idiopathic nephrotic syndrome. The zeta (zeta) chain, which is a component of the
      TCR/CD3 complex and CD16 heterodimer in NK cells, plays a crucial role in signal
      transducing events leading to T and NK cell activation and proliferation. The aim
      of our study was to examine the zeta (zeta) chain expression in peripheral blood
      CD4+, CD8+ T-lymphocytes and NK cells (CD3-/CD56+) derived from children with NS
      in active phase of the disease and in remission. We also examined the effect of
      24 and 72 h anti-CD3+rIL-2 stimulation on the zeta chain expression in all
      studied groups. MATERIAL AND METHODS: The study group consisted of 8 children
      with INS in active phase of the disease, 11 children with INS in clinical
      remission and 15 age-matched healthy controls. The level of zeta (zeta) chain
      expression, assessed by flow cytometry, was determined as the mean fluorescence
      intensity (MFI). RESULTS: In INS patients with active phase MFI values for CD4+
      cells were higher than in children with remission and in controls. The levels of
      zeta in CD4+ T-lymphocytes of patients with remission were comparable to those in
      controls. There were no differences between zeta levels on NK cells in examined
      groups. Ex vivo stimulation had no impact on zeta expression in children with
      acute phase of NS, whereas in patients on remission stimulation with anti-CD3+rIL
      2 increased zeta expression on CD4+ cells and decreased it on NK cells. NK zeta
      expression was also diminished in the control group. CONCLUSIONS: Preliminary
      results point at the alterations of zeta expression in children with INS as a
      probable cause of immune dysregulation in this group of patients.

PMID- 16898535
TI  - [Insulinsensitivity and beta-cell function in children with idiopathic nephrotic
      syndrome].
AB  - Glucose intolerance which is frequently found in patients with the idiopathic
      nephrotic syndrome (INS) may be linked to an increased cardiovascular risk in
      these patients. Recently it has been suggested that proteinuria and steroid
      treatment may independently affect insulin sensitivity. The aim of the study was
      to assess insulin resistance (IR) and beta-cell function in children with INS at
      various stages of the disease. The study group comprised 66 children (32 male, 34
      female; age 8.1 +/- 5.0 years). 20 healthy, sex- and age-matched subjects served
      as controls. The study group was divided into 3 subgroups: A (n=24) children in
      relapse of INS (steroids 60 mg/m2/48h; proteinuria 1.02 +/- 1.04 g/dl); B (n=20)
      in remission treated with steroids (30 mg/ m2/48h); C (n=22) in remission but
      without steroids. Fasting glucose and insulin levels were measured to calculate
      insulin resistance (HOMA-IR) and beta-cell function (HOMA-beta) using Homeostatic
      Model Assessment. Fasting glucose was within normal range in all subjects. HOMA
      IR was significantly higher in group A (3.2 +/- 3.3) and group B (2.4 +/- 1.7)
      than in group C (1.45 +/- 1.6 and controls (1.12 +/- 0.6) (p<0.05). HOMA-beta was
      significantly higher in group A and B than in C and controls (p<0.05). In
      multivariate analysis HOMA-IR correlated with proteinuria (beta=0.45, p<0.001),
      steroid dose (beta=0.32) and BMI (beta=0.42). In conclusion, an increase in
      insulin resistance with compensatory enhanced beta-cell secretion is a typical
      finding in children with INS treated with steroids. Proteinuria seems to be an
      independent risk factor for decreased insulin sensitivity.

PMID- 16898534
TI  - [Assessment of the peripheral circulation in children with nephrotic syndrome
      treated with cyclosporin A].
AB  - Cyclosporin A (CsA) is an immunosuppressive agent used in children for the
      treatment of steroid-dependent idiopathic nephrotic syndrome (INS). Despite its
      benefitial effect on a course of the disease CsA may exert nephrotoxic effects
      because of its vasoconstrictive properties. CsA-dependent disorders of the
      peripheral flow (Raynaud phenomenon--RP) have been recently described. The aim of
      the study was to assess the effect of CsA on the peripheral circulation. The
      study group comprised 16 children (12 male, 4 female; mean age 9.8 +/- 4.5 years)
      treated with CsA for at least 6 months due to INS (mean treatment time 39 +/- 27
      months). Thirteen age- and sex-matched individuals served as controls. Peripheral
      circulation disorders were evaluated by means of a cold stress test (both hands
      were held in lukewarm water (20 degrees C) for 1 minute and thereafter the
      changes in the hand temperature were recorded with thermographic camera
      (Inframetrics SC1000). RP assessment was performed according to the method
      described by Ammer and Ring. The temperature gradient of 4 degrees C or greater
      maintained between metacarpal and peripheral areas of a hand after 10 minutes was
      considered diagnostic for RP. According to these criteria RP was confirmed in
      only 3 patients from the study group and in 2 controls. However, the time of the
      temperature increase in the first 5 minutes after cooling was considerably
      shorter in the children with INS (0.26 +/- 0.26 degrees C/min vs 0.51 +/- 0.29
      degrees C/min, p=0.02). No correlation between CsA serum concentration, CsA dose
      and impairment of the hand temperature increase was found. The study confirmed
      that in children suffering from INS treated with CsA peripheral blood flow
      disorders can be seen. It seems that impaired vessel reactivity may result from
      the vasoconstrictive effect of CsA.

PMID- 16898536
TI  - [Acquired Fanconi-de Toni-Debre syndrome due to therapy for Ewing's sarcoma in 5
      years old boy].
AB  - We present a 5-years old boy with acquired Fanconi-de Toni-Debre syndrome being a
      effect of therapy for Ewing's sarcoma. At the age of 3 years, this boy was
      diagnosed as suffering from Ewing sarcoma of his right femur. The boy received a
      course of 8-month pre-surgery (6 VIDE--Vincristine, Ifosfamide, Doxorubicin,
      Etoposide cycles and 2 VAI--Vincristine, Actinomycin, Ifosfamide cycles) and 6
      month post-surgery (6 VAI--Vincristine, Actinomycin, Ifosfamide cycles)
      cytostatic therapies according to EWING, EURO 99 protocol. In forth month of post
      surgery cytostatic therapy, progressive malaise, polyuria, polydypsia, and
      recurrent vomiting occurred. The association between those symptoms and
      malignancy was excluded. Laboratory studies revealed hypokaliemia,
      hypophosphatemia, proximal tubular acidosis, proteinuria, glucosuria,
      aminoaciduria, hyperkaliuria and hyperphosphaturia. Acquired Fanconi-de Toni
      Debre syndrome due to toxic effect of cytostatic therapy on renal proximal
      tubules was diagnosed. At present, two years after the time the diagnosis was
      made, despite constant substitution of potassium, phosphates and bicarbonates,
      deficit of body mass and height, and bone mineral density abnormalities are
      observed.

PMID- 16898537
TI  - [Successful prophylactic plasma infusions in recurrent atypical hemolytic-uremic
      syndrome].
AB  - Atypical, recurrent hemolytic uraemic syndrome (HUS) often leads to end-stage
      renal disease and can relapse after a renal transplantation. Plasmapheresis and
      fresh frozen plasma (FFP) therapies are used to treat acute relapses. We report
      on the prophylactic use of FFP in a child with atypical recurrent HUS with low
      serum C3. The girl experienced four episodes of atypical HUS over a year from the
      age of 18 months. During the first relapse a decreased level of C3--0,62 g/l
      (normal: 0.88-2.01 g/l) was revealed. Initially daily plasma infusions were given
      (8-14 ml/kg for 5-15 days) during acute episodes. Following the 4th episode
      prophylactic FFP therapy was started. Three-times weekly plasma transfusions were
      continued for three months and then doses were tapered off over the next months
      to once-weekly FFP. During the one year follow-up no relapse has been observed.
      At the age of 3 1/2 years she is thriving (10th percentile for height and
      weight). She has severe but well controlled hypertension without end-organ
      involvement. The child demonstrates signs of stage 2 chronic kidney disease
      (CKD): serum creatinine--0.65 mg/dl, Schwartz estimated GFR--79.9 ml/min/ 1.73
      m2, persistent slight proteinuria and haematuria, increased renal cortical
      echogenicity on ultrasound. Genetic studies for the known atypical HUS mutations
      and assessment of complement activation proteins (factors H and I) are under
      investigation. CONCLUSION: Prophylactic FFP infusions can be successful in
      preventing relapses and further progressive renal damage in individual patients
      with atypical HUS associated with low C3.

PMID- 16898538
TI  - [The comparative study on selective alpha1-blocker and behavioural therapy in the
      treatment of discoordinated voiding in children].
AB  - PURPOSE: To compare the efficiency of selective alpha1-blocker and behavioural
      therapy in the treatment of detrusor-sphincter discoordination in children.
      MATERIALS: Prospective, randomized study, approval of Ethics Committee, group of
      60 children, age: 5 to 17, detrusor-sphincter discoordination. All children had a
      history of: recurrent UTI, irregular mictions with or without incontinence in
      "voiding diary". All have normal upper urinary tract in USG. Dicoordination was
      diagnosed by pathologic uroflowmetry curve and results with significant
      postvoiding residual urine in USG. Treatment group 1 (n=30): treatment with
      selective alpha1-blocker (doxazosin) in age related dosage. Group 2 (n=30):
      behavioral therapy and rehabilitation with conducting "voiding diary" with timed
      voiding. All children were also instructed on proper toilet posture, relaxation
      of the pelvic-floor muscles. After 6 weeks: changes in voiding patterns: No. of
      micturitions/day, average voided volume were estimated. Uroflowmetry was
      performed and voided volume, Av. flow rate, shape of the curve (1=normal,
      2=flatened, irregular, 3=portions), residual urine (10% of Void.vol.) were
      calculated. Urinalysis and urin culture were obtained. RESULTS: Of 60 children 57
      completed the study: Group 1 (n=30), Group2 (n=27). In Group 1 (alpha1-blocker):
      improvement in voiding patterns n=21, improvement in UF parameters n=20. In Group
      2 (rehabilitation): improvement was estimated in 17 patients. Side effects were
      noted in 6 children from Group 1 (alpha1-blockers) (headache, hypotonia, vertigo,
      epistaxis), and non from the Group 2 (rehabilitation). CONCLUSIONS: Both
      treatment methods seemes to be effective in detrusor-sphincter discoordination.
      Selective alpha1-blockers alone are more effective than training and
      rehabilitation exercises.

PMID- 16898539
TI  - [The system of management nocturnal enuresis based on functional classification].
AB  - The aim of the study was to describe our diagnostic and therapeutic logarithm
      based on functional classification in children with enuresis, and effects of
      therapy based on this classification. MATERIALS AND METHODS: we reviewed charts
      of 123 children managed because of nocturnal enuresis (68 boys, 55 girls, aged 4
      18 (mean 7,6) years). Every child had routinely performed ultrasonography,
      urinalysis, uroflowmetry with estimation of residual urine. Children with urinary
      tract infections or malformations of the urinary tract were not included in this
      study. At the first visit all children were instructed to conduct voiding diary.
      On the base of data from voiding diarys and uroflowmetries children are divided
      in two groups: Group I (n=21) with monosymptomatic nocturnal enuresis. Group II
      (n=102) children with bladder dysfunction and enuresis. In the first group
      rehabilitation program with bladder training, conducting voiding diary and
      conditioning therapy with alarm device was introduced. In children with bladder
      dysfunctions therapy started with bladder training and pharmacotherapy of bladder
      dysfunction. RESULTS: 9 children (6 from Group I and 3 from Group II) started to
      wake after starting bladder training. 81 children from Group II improved bladder
      function. 30 children from Group II started to wake up during therapy of bladder
      dysfunction. In 44 children, who improved bladder function and still had episodes
      of nocturnal enuresis, therapy with alarm device was introduced. From all 66
      children treated with alarm device 5 started to wake up without any one episode
      of wetting. In 20 children the ability to wake up before alarm started to ring
      occurred in the first month of therapy. 40 children need to be treated for the
      second month, in 5 children therapy was prolonged for the third month. 9 children
      did not learn to wake up for urination. We have 8 drop-outs. In 7 therapy was
      repeated because of recurrence. CONCLUSION: The system of treatment of nocturnal
      enuresis is effective both in children with monosymptomatic nocturnal enuresis
      and in children with enuresis and voiding dysfunction.

PMID- 16898540
TI  - Proof or consequences. Law to curb illegal immigrants' Medicaid coverage may
      sting U.S. citizens seeking medical treatment without documentation.
AB  - By requiring providers to ask Medicaid patients to prove citizenship, the
      government is creating a quandary: providers can comply and potentially lose
      millions in reimbursements or forfeit matching funds if they don't. Ironically,
      the mandate could cause millions of eligible patients to lose health coverage
      because they can't supply the documents, says Ron Pollack, left.

PMID- 16898542
TI  - Tenet continues divesting. Nine hospitals in Fla., La., Pa. also put on the
      block.

PMID- 16898541
TI  - Outlier probe may widen. Consultancies may be next to come under scrutiny.

PMID- 16898543
TI  - Reassessing CON laws. Scrushy verdict raises questions on process' integrity.

PMID- 16898544
TI  - High quality, low mortality? Top-notch care not necessarily a lifesaver: study.

PMID- 16898546
TI  - Board, quality linked: study.

PMID- 16898545
TI  - JCAHO rival has setback. TUV must reapply for CMS deeming authority.

PMID- 16898547
TI  - Wis. tackles healthcare costs. Badger State eyes reinsurance, improved access.

PMID- 16898548
TI  - Carilion's worthy gamble. Clinic model carries promise of focus on quality and
      cost-efficiency.

PMID- 16898549
TI  - The real work's still to come. Massachusetts' access plan hinges on controlling
      costs, improving quality.

PMID- 16898550
TI  - Personal and (maybe) confidential. Questions over privacy, formats and
      definitions remain, but personal health records are on the way.

PMID- 16898551
TI  - By the numbers. 20 largest healthcare executive search firms ranked by number of
      U.S. placements made for senior-level (senior VP and above) healthcare executives
      in 2005.

PMID- 16898552
TI  - Arming for an emergency. Hospitals may be more ready for a pandemic now than a
      year ago, but experts say some preparations are just lip service.
AB  - After months of work and millions of dollars awarded to state and local
      governments, U.S. hospitals are still less than ready to face a pandemic or
      bioterrorism-related emergency, according to disease experts. But it's difficult
      to be completely prepared for such an event, they say. "You don't know when it's
      going to come, where it will be, whether you'll have medicines to fight it," says
      Tammy Lundstrom, left.

PMID- 16898554
TI  - N.J. Blues will offer rewards.

PMID- 16898553
TI  - Part D outdoes expectations. But providers may face more cuts in reimbursement.

PMID- 16898555
TI  - Opening up the process.

PMID- 16898556
TI  - Appeal goes healthcare's way.

PMID- 16898557
TI  - Home-care demands rise. Medicaid key to helping seniors remain in abodes.

PMID- 16898558
TI  - The cost of bad behavior in OR. Docs' nurses' actions linked to adverse events:
      study.

PMID- 16898559
TI  - Part D callers get wrong 411.

PMID- 16898560
TI  - Flexibility and humility. When it comes to healthcare reform, all conclusions may
      be premature.

PMID- 16898561
TI  - Bigger payday for some docs. Our annual survey shows increases, especially in
      primary care, but rising inflation blunts pay raises in most medical specialties.

PMID- 16898562
TI  - Bridging the gap. Practice administrator job evolves.

PMID- 16898563
TI  - Reconciling God and science.

PMID- 16898564
TI  - The intimate life of A. Einstein.

PMID- 16898565
TI  - Do I know you?

PMID- 16898566
TI  - More than just a little chunky.

PMID- 16898567
TI  - A public health approach to the diabetes epidemic: New York City's diabetes
      registry.

PMID- 16898568
TI  - Fatty acid-induced inflammation and insulin resistance in skeletal muscle and
      liver.
AB  - Plasma free fatty acid (FFA) levels are elevated in obesity. FFA, by causing
      insulin resistance in muscle, liver, and endothelial cells, contributes to the
      development of type 2 diabetes mellitus (T2DM), hypertension, dyslipidemia, and
      nonalcoholic fatty liver disease (NAFLD). The mechanism through which FFA induces
      insulin resistance involves intramyocellular and intrahepatocellular accumulation
      of triglycerides and diacylglycerol, activation of several serine/threonine
      kinases, reduction in tyrosine phosphorylation of the insulin receptor substrate
      (IRS)-1/2, and impairment of the IRS/phosphatidylinositol 3-kinase pathway of
      insulin signaling. FFA also produces low-grade inflammation in skeletal muscle
      and liver through activation of nuclear factor-kappaB, resulting in release of
      several proinflammatory and proatherogenic cytokines. Thus, elevated FFA levels
      (due to obesity or to high-fat feeding) cause insulin resistance in skeletal
      muscle and liver, which contributes to the development of T2DM, and produce low
      grade inflammation, which contributes to the development of atherosclerotic
      vascular diseases and NAFLD.

PMID- 16898569
TI  - Development of type 2 diabetes in children and adolescents.
AB  - Type 2 diabetes is emerging as a significant health problem in children and
      adolescents. The disease usually develops in obese insulin-resistant youth with a
      typical pattern of lipid partitioning characterized by increased lipid deposition
      in myocytes, the visceral compartment, and the liver. Unfavorable adipocytokine
      profiles, together with a state of low-grade inflammation, create an additional
      metabolic burden tightly coupled to other components of the metabolic syndrome.
      Insufficient beta-cell compensation promotes altered glucose metabolism.

PMID- 16898570
TI  - Central nervous system and control of endogenous glucose production.
AB  - Recent evidence points to the crucial role of the central nervous system in
      controlling glucose homeostasis. Hypothalamic centers involved in the regulation
      of energy balance and endogenous glucose production constantly sense fuel
      availability by receiving and integrating inputs from circulating nutrients and
      hormones such as insulin and leptin. In response to these peripheral signals, the
      hypothalamus sends out efferent impulses that restrain food intake and endogenous
      glucose production. This promotes energy homeostasis and keeps blood glucose
      levels in the normal range. Disruption of this intricate neural control is likely
      to occur in type 2 diabetes and obesity and may contribute to defects of glucose
      homeostasis and insulin resistance common to both diseases. This review
      summarizes the latest findings on the hypothalamic control of endogenous glucose
      production, and focuses on the central effects of circulating macronutrients and
      nutrient-induced hormones.

PMID- 16898572
TI  - The DREAM trial and the prospect of diabetes prevention.

PMID- 16898571
TI  - Incretins and the development of type 2 diabetes.
AB  - The incretin hormones gastric inhibitory polypeptide (GIP) and glucagon-like
      peptide 1 (GLP-1) are released in response to nutrient ingestion and potentiate
      glucose-stimulated insulin secretion from pancreatic beta cells. The augmentation
      of postprandial insulin secretion by such gastrointestinal hormones is called the
      incretin effect. The incretin effect is almost completely absent in patients with
      type 2 diabetes. This is due to 1) an approximate 15% reduction in postprandial
      GLP-1 secretion and 2) a near total loss of insulinotropic activity of GIP. This
      review article summarizes clinical studies on abnormalities in the secretion and
      insulinotropic effects of GIP and GLP-1 in patients with type 2 diabetes as well
      as in individuals at high risk. A significant proportion of first-degree
      relatives are characterized by a reduced insulinotropic response to exogenous
      GIP. Nevertheless, this phenomenon does not predispose to a more rapid
      deterioration in glucose tolerance or conversion to impaired glucose tolerance or
      diabetes. Therefore, although there are hints of early abnormalities in incretin
      secretion and action in prediabetic populations, it has not been proven that such
      phenomena are central to the pathogenesis of type 2 diabetes.

PMID- 16898573
TI  - Cardiometabolic syndrome and chronic kidney disease.
AB  - Chronic kidney disease (CKD) is increasingly recognized as a major risk factor
      for end-stage renal disease (ESRD), cardiovascular (CV) disease, and CV-related
      premature death. More than 8 million people in the United States have CKD;
      therefore, preventive stratiegies should be directed at identifying risk factors
      for this condition. There is growing evidence implicating the cardiometabolic
      syndrome, a clustering of CV risk factors that include obesity, insulin
      resistance, compensatory hyperinsulinemia, dysglycemia, atherogenic dyslipidemia,
      and hypertension. Factors mediating this relationship include increased
      glomerular filtration, increased vascular permeability, oxidative and endoplasmic
      reticulum stress, activation of the renin-angiotensin system, and inappropriate
      secretion of growth factors. The consequences are microalbuminuria, a marker of
      inflammation and endothelial dysfunction, renal vascular proliferation,
      extracellular matrix expansion, and CKD. Prevention of CKD should be directed at
      controlling all components of the cardiometabolic syndrome, with the ultimate
      goal of reducing the burden imposed by ESRD.

PMID- 16898574
TI  - Anemia and cardiovascular disease in diabetic nephropathy.
AB  - Cardiovascular disease (CVD) is the major cause of morbidity and mortality in
      people with diabetes and in those with chronic kidney disease (CKD). Diabetes,
      occurring in epidemic proportions in the United States and worldwide, is also the
      leading cause of CKD and kidney failure. Identification of modifiable risk
      factors for CVD in patients with diabetes and CKD is thus of paramount
      importance. Anemia is increasingly recognized as a potential CVD risk factor in
      patients with diabetic nephropathy, in whom it is generally more severe and
      occurs at an earlier stage of CKD. In this review, we discuss the epidemiologic
      evidence, pathophysiologic mechanisms, and the current research findings,
      highlighting the role of anemia as a potential modifiable risk factor for CVD in
      patients with diabetic nephropathy, a particularly vulnerable population for CVD.

PMID- 16898575
TI  - Gender disparity in outcomes of care and management for diabetes and the
      metabolic syndrome.
AB  - Although diabetes lies among the major risk factors for cardiovascular disease
      (CVD) in both men and women, current evidence suggests that it has a much
      stronger effect on the risk of coronary heart disease (CHD) in women than in men.
      Moreover, diabetic women have not experienced the decline in CHD mortality
      observed in diabetic men and individuals without diabetes over the past three
      decades. Apart from a more pronounced direct effect of diabetes on the vascular
      wall, this greater impact of diabetes on CHD risk in women could be associated
      with a heavier burden of other traditional cardiovascular risk factors within the
      context of the metabolic syndrome, a stronger effect of the metabolic syndrome on
      CVD, and a less aggressive management of the various risk factors in diabetic
      women compared with men. This article discusses the recent evidence on the gender
      differences in the outcomes of CVD and the management of risk factors associated
      with diabetes and the metabolic syndrome, highlighting the need for better
      treatment strategies of diabetes and the other components of the metabolic
      syndrome in diabetic women.

PMID- 16898576
TI  - Intensive insulin therapy: is it effective in the medical intensive care unit?

PMID- 16898577
TI  - Rimonabant--the RIO North America trial: a new strategy to sustaining weight loss
      and related morbidity.

PMID- 16898578
TI  - Treatment of hypertriglyceridemia.
AB  - Hypertriglyceridemia is a disorder commonly encountered in clinical practice.
      Treatment of this condition aims to prevent the major complications of
      hypertriglyceridemia, which differ depending on whether triglyceride elevations
      are moderate or severe. This review discusses the pathophysiology and clinical
      consequences of hypertriglyceridemia and outlines treatment approaches based on
      the degree of triglyceride elevation. Special consideration is given to clinical
      trials using medications that primarily target triglycerides.

PMID- 16898579
TI  - Type 2 diabetes and the metabolic syndrome in children and adolescents.
AB  - The prevalence rates of obesity, metabolic syndrome, and type 2 diabetes in
      children are increasing at an alarming rate. The potential impact of these
      conditions on the individual, the family, and society, especially in regard to
      the costs and utilization of health care resources, are very serious. Strategies
      aimed at reducing caloric intake, increasing caloric expenditure through regular
      exercise, and treating cardiovascular risk factors and type 2 diabetes early and
      aggressively are necessary to meet the challenges they impose.

PMID- 16898581
TI  - [The role of macroglobulin family proteins in the regulation of inflammation].
AB  - The macroglobulin family represents a group of universal regulators involved into
      control of the inflammatory response to external and internal pathogens. Alpha-2
      macroglobulin (MG), the major protein in the family, has 3 different binding
      sites and high affinity to an endocytosis receptor that allows MG to participate
      in recognition and phagocytosis of the foreign agents. The macroglobulin family
      proteins are most powerful apoptosis inhibitors: they bind autoaggressive
      hydrolases accumulating during inflammation. MG is the main transporter of
      cytokines and growth factors controlling the inflammatory response. At the same
      time, the macroglobulins are negative reactants of an acute phase of inflammation
      and the decrease of their synthesis at later stages is necessary for stimulation
      of collagenosis processes, coagulation, activation of thymulin, stimulating NK.
      At septic inflammation binding of macroglobulins to exotoxins can localize
      inflammation, and initiate systemic inflammatory response. Macroglobulin damage
      sharply reduces their subsequent utilization; this provokes accumulation of
      makroglodulin-proteinase complexes in biological fluids and may cause immune
      inflammation.

PMID- 16898580
TI  - The role of complementary and alternative medicine in diabetes.
AB  - Complementary and alternative medicine (CAM) describes a diverse group of medical
      and health care systems, practices, and products not currently considered to be
      part of conventional medicine. Inadequacies in current treatments for diabetes
      have led 2 to 3.6 million Americans to use CAM for diabetes treatment, despite
      limited studies of safety and efficacy of CAM methods. CAM is used mostly by West
      Indians, Africans, Indians, Latin Americans, or Asians. Prayer, acupuncture,
      massage, hot tub therapy, biofeedback, and yoga have been used as well as various
      plant remedies for treating diabetes. Several CAM practices and herbal remedies
      are promising for diabetes treatment, but further rigorous study is needed in
      order to establish safety, efficacy, and mechanism of action. In the meantime, it
      is important to be aware that many patients with diabetes may be using CAM and to
      consider potential interactions with conventional medicines being used.

PMID- 16898582
TI  - [Genomics. Diversity of human nature].

PMID- 16898583
TI  - [Stable transfection of DAOY cells with a GM3 synthase antisense construct and
      transient reduction in ganglioside content].
AB  - Tumor cell gangliosides are bioactive molecules involved in tumor-host
      interactions. To investigate their role in tumor formation and angiogenesis, we
      sought to develop an inhibitory model targeting human GM3 synthase, an essential
      enzyme in the ganglioside synthesis pathway, by antisense transfection. We
      prepared a number of transfectants from DAOY human medulloblastoma cells and
      isolated clones that stably expressed a 560-bp fragment of human GM3 synthase
      cDNA, in either sense or antisense orientation, as well as clones transfected
      with an empty vector. Both sense and antisense clones permanently incorporated
      mammalian expression vectors into their genomes. The DAOY cell clones were
      screened for ganglioside content using total lipid extraction, ganglioside
      isolation, and HPTLC. One antisense-transfected clone, 7.2A, in which total
      ganglioside content was reduced by 70%, was selected for further study. All sense
      and sham-transfectants had ganglioside levels not different from that of
      untransfected DAOY cells. After 10 passages however, while antisense mRNA
      expression was fully maintained, the ganglioside content of 7.2A cells had
      reverted to normal levels. Antisense RNA transfection can sometimes have a
      reversible effect on the expression of a target. Possible regulatory mechanisms
      of this previously unrecognized process of reversion to wild type phenotype are
      discussed.

PMID- 16898584
TI  - [Oligomerization of L-asparaginase from Erwinia carotovora].
AB  - Bacterial L-asparaginases catalyzing hydrolysis of L-asparagine up to L-aspartate
      and ammonia, are used in medical practice for treatment of acute lymphoblastic
      leukemia. The long-term therapy with these preparations is accompanied by a
      number of side effects, which are attributed to glutaminase activity of L
      asparaginase. Substrate specificity and activity of L-asparaginases are directly
      associated with the process of enzyme oligomerization. It is active only in the
      tetrameric form as the active sites are located in contact areas between
      monomers. The present work is devoted to homology modeling of spatial structure
      of L-asparaginase from Erwinia carotovora, the comparative molecular-graphic
      analysis of subunits interfaces, as well as development of experimental approach
      for enzyme oligomerization study. L-asparaginase was immobilized on a CM5 chip
      surface of optical biosensor Biacore 3000 based on the surface plasmon resonance
      technology. The dissociation process of enzyme tetrameric complexes up to
      monomers and subsequent oligomerization process have been registered.

PMID- 16898585
TI  - [Characteristics of post-stress changes of lipid peroxidation and stress-limited
      effects of alpha-tocopherol in liver and serum of infant and old rats].
AB  - The process of lipid peroxidation (LPO) and the effects of alpha-tocopherol were
      studied in the liver and blood serum of albino male rats under acute
      immobilization stress. The results of the research show tissue and age specific
      responses of LPO in the intact and stressed animals. Pretreatment of animals with
      alpha-tocopherol decreased accumulation of LPO products especially in the liver.

PMID- 16898586
TI  - [Regulatory properties of glucose-6-phosphate dehydrogenase from rat liver under
      conditions of the intensification of free-radical oxidation stimulated by toxic
      hepatitis].
AB  - Rat liver oxidative stress caused by toxic hepatitis is accompanied by increased
      activity of glucose-6-phospate dehydrogenase (EC 1.1.1.4.9; G6PDG).
      Electrophoretically homogenous G6PDG preparations purified from livers control
      rats and animals with hepatitis had specific activity of 4.13 and 6.54 EU,
      respectively. Fe2+ and Cu2+ ions showed non-competetive type inhibition of G6PDG
      at normal and under pathological condition, whereas Ca2+ activated G6PDG.
      Hydrogen peroxide exhibited mixed type inhibition of G6PD (K(i) 0.36 mM and 0.95
      mM at norm and experimental toxic hepatitis, respectively). The participation of
      oxidised and reduced glutathione in G6PDG activity regulation has been shown.

PMID- 16898587
TI  - [Correlation between succinate-dependent Ca2+ accumulation and transamination in
      the heart and the liver mitochondria of experimental animals].
AB  - Glutamate (GLU) and alpha-ketoglutarate (KGL), the substrates involved in
      transamination, have reciprocal effects on succinate-dependent respiration, NADH
      reduction, as well as on the accumulation and stable retention of Ca2+ in heart
      and liver mitochondria and homogenates from experimental animals. The succinate
      dependent Ca2+ accumulation was shown to be highly sensitive to changes of the
      concentration ratios of GLU and KGL within the range 1:10 mM. GLU activated this
      process by transamination of oxalacetate (OAA) to aspartate. The predomination of
      KGL blocked the activating effect of GLU. The predomination of GLU eliminated the
      block produced by KGL or phosphoenolpyruvate (sources of OAA and GTP) but did not
      eliminate the Ca2+ accumulation-suppressing effect of aminoacetate, inhibitor of
      transaminases.

PMID- 16898588
TI  - [Effect of steroid biosynthesis modificators on the progesterone
      biotransformation by a recombinant yeasts expressing cytochrome P450c17].
AB  - Using the recombinant microorganisms S. cerevisiae GRF18 YEp5117alpha, expressing
      cytochrome P450c17 from bovine adrenal cortex, we investigated the influence of
      the various modificators of steroids biosynthesis on the relationship between the
      17alpha-hydroxylation of progesterone and 20alpha-reduction. Dexamethasone and
      metirapon had no effect on the reaction of progesterone 17alpha-hydroxylation and
      on the reaction of 17alpha-hydroxyprogesterone 20alpha-reduction. Mifepriston and
      danazol did not covalently modify amino acid residues of the cytochrome P450c17
      or its heme group under the conditions of the biotransformation of progesterone
      by recombinant yeasts. Ketokonazol, mifepriston and danazol acted as low-affinity
      competitive inhibitors, but the 20-dihydro derivatives of progesterone were mixed
      type inhibitors for the cytochrome P450c17. All modifiers that we used did not
      influence the functional properties of the yeast analog of 20alpha-hydroxysteroid
      dehydrogenase. According to the influence on the catalytic parameters of the
      cytochrome P450c17, the modifiers used can be arranged in the following order:
      20beta-dihydroprogesterone (maximum effect) > mifepriston = ketokonazol > 20alpha
      dihydroprogesteron > danazol > dexamethasone, metirapon (without effect).

PMID- 16898589
TI  - [Biochemical and pharmacological mechanisms of different types of hypoxic
      preconditioning in cerebral ischemia in mice].
AB  - Different types of hypoxic preconditioning (hypoxic, circulatory, hemic and
      tissue hypoxia) increase the tolerance to complete global cerebral ischemia at
      early terms (hours). Biochemico-pharmacological analysis with the use of
      selective agonists and antagonists showed the importance of adenosine A1
      receptors and K+(ATP)-channels in the mechanisms of the neuroprotective effect
      and natural tolerance. The general scheme of the investigated mechanisms of
      different types of hypoxic preconditioning has been proposed.

PMID- 16898590
TI  - [Lymphocyte metabolism in patients with acute pancreatitis with different
      genotypes of GSTM1 and GSTT1 genes].
AB  - In this study, we have investigated correlation between enzymatic activity of
      NAD(P)-dependent dehydrogenases of lymphocytes and polymorphic variants of
      glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) genes in the group of
      unrelated patients with acute pancreatitis in comparison with healthy Russians
      from Krasnoyarsk. Thus, genotype GSTM1 0/0 is the marker of predisposition to the
      acute pancreatitis, wheras polymorphism of the GSTT1 gene is not involved in the
      development of the pancreatitis, at least in our group. The bioluminescence
      analysis showed statistically significant decrease of the levels of G3PD,
      NAD(+)MDH and the increase of NADH(+)LDH, NAD(+)GDH, NADH(+)GDH in lymphocytes of
      pancreatic group. Development of pancreatitis in patients with different
      genotypes GSTM1 and GSTT1 genes showed the rearrangement of the basic
      intracellular processes: dominance of a plastic metabolism in the patients with
      GSTM1--deletions and predominance of energetic processes at GSTT1 0 -
      pancreatitis.

PMID- 16898591
TI  - [Changes in erythrocyte superoxide dismutase and catalase activity in premature
      newborns with intraventricular haemorrhages].
AB  - Superoxide dismutase and catalase activities have been studied in peripherical
      blood erythrocytes of 49 premature newborns at 28-37 weeks gestation. Superoxide
      dismutase and catalase activities were lower in patients with bacterial infection
      of meninges. The standard therapy did not restore superoxide dismutase and
      catalase activities by the end of the neonatal period.

PMID- 16898592
TI  - [Epidemiologic investigation on incidences of urological malignant tumors for 10
      years in eastern part of Yamaguchi prefecture].
AB  - OBJECTIVE: In Japan, there is not enough information regarding the incidences of
      cancer, especially in the field of urology. In order to investigate the accurate
      occurrence of urological malignant tumors, an epidemiologic study was conducted
      in the eastern part of Yamaguchi prefecture over a period of 10 years. METHOD:
      The target areas for this study were 8 cities (Yamaguchi city, Hofu city, Shin
      nanyo city, Tokuyama city, Kudamatsu city, Hikari city, Yanai city and Iwakuni
      city), and 7 districts (Oshima Gun, Kuga Gun, Kumage Gun, Tsuno Gun, Saba Gun,
      Abu Gun and Yoshiki Gun) in eastern Yamaguchi prefecture. The investigation
      period was 10 years: i.e. 1994-2003. Urological malignant tumors in this study
      were bladder cancer, tumors of the renal pelvis and ureter, renal cell carcinoma,
      prostatic carcinoma and testicular tumor. RESULT: Age-adjusted incidence rates
      for bladder cancer per 100,000 per year by world population from 1994 to 2003
      were 11.26-15.88 for male and 1.91-3.15 for female. The age-adjusted incidence
      rates for prostatic carcinoma were 10.57-41.78. The age-adjusted incidence rates
      for tumors of the renal pelvis and ureter were 0.76-1.81, for renal cell
      carcinoma 1.85-2.68 and for testicular tumor 1.85-2.68.

PMID- 16898593
TI  - [Clinical analysis of bladder cancer].
AB  - PURPOSE: We report our clinical experiences of treatment for bladder cancer.
      MATERIAL AND METHODS: Clinical analysis was performed about 282 primary bladder
      cancer patients who performed first time treatment in our hospital from January
      1991 to December 2002. RESULTS: As to T classification, 127 patients were in Ta,
      89 in T1, 27 in T2,18 in T3, eight in T4 and 13 in Tis, respectively and among
      those, there were seven patients with a metastasis. Most patients of superficial
      cancer were treated by combined use of TUR and instillation therapy. There were
      few patients of total cystectomy performed as a first time treatment in the case
      of invasive cancer in our clinic and comparatively many preservation therapies by
      TUR, systemic chemotherapy and radiotherapy combined use were performed. Cancer
      recurred to 90 cases in 275 patients, and 18 patients died owing to cancer
      progression. Five and ten-years-recurrence free rate in the whole were 59.5 and
      44.3%, five and ten-years-disease specific survival rate were 92.9 and 85.9%.
      Furthermore, 5-years-disease specific survival rate classified by T stage were
      100, 100, 71.2, 46.7 (3-years-survival), 53.6, 83.3% in Ta, T1, T2, T3, T4, Tis,
      respectively and the significant difference was observed. The disease specific
      five-years survival rate of the whole local invasive carcinoma (T2-4N0M0) was
      57.5% and 70.2% in the case of preservation therapy performed by TUR,
      chemotherapy and radiotherapy combined use. CONCLUSIONS: An appropriate treatment
      according to the each case is needed for bladder cancer.

PMID- 16898594
TI  - [8-month neoadjuvant hormonal therapy before radical prostatectomy for high-risk
      prostate cancer].
AB  - PURPOSE: To evaluate the clinicopathological outcomes of 8 months of neoadjuvant
      hormonal therapy (NHT) prior to radical prostatectomy for high-risk prostate
      cancer. PATIENTS AND METHODS: A multi-institutional prospective trial was
      performed between July 2000 and May 2003 involving high-risk prostate cancer
      patients without metastasis, including 21 who received 8 months of NHT before
      radical prostatectomy. High-risk group was defined as clinical stage > or =T2c
      and/or prostate-specific antigen (PSA) >20 ng/ml and/or Gleason score > or =8.
      PSA values were considered elevated (biochemical failure) if values of 0.1 ng/ml
      or greater were obtained. RESULTS: Median of initial PSA levels before prostate
      biopsy was 27.6 ng/ml (8.5-80.7 ng/ml), and median of pre-operative PSA levels
      after NHT was 0.28 ng/ml (0.02-4.2 ng/ml). There were 5 patients (23.8%) with
      lower limit of PSA detection (less than 0.02 ng/ml) in 8 months after NHT. The
      clinical T stage was T1c in 9 patients (42.9%), T2a-b in 8 patients (38.1%), T2c
      in 3 patients (14.3%), and T3a in 1 patient (4.8%). The median follow-up was 25
      months (range 4 to 37). There were 2 patients (9.5%) in pT0, 5 patients (23.8%)
      with positive surgical margin, 5 patients (23.8%) with extracapsular extension
      (ECE) and 3 patients (14.3%) with seminal vesicle involvement (SVI). Biochemical
      failure was occurred in 9 of 21 (42.9%) including of one pT0. Range of time to
      postoperative biochemical failure was 2 to 25 months (median 6 months) and most
      of biochemical failure was found within 12 months after surgery. Biochemical
      failure rate was significantly higher in patient with positive SVI (p = 0.0308)
      and higher in patients with pre-operative PSA levels of more than 0.1 ng/ml (p =
      0.0836), positive ECE (p = 0.0545) and positive surgical margin (p = 0.0545).
      CONCLUSION: Biochemical failure was frequent after this combined treatment, even
      in a pT0 case. Long-term follow-up of patients is needed to assess the impact of
      this therapy on mortality.

PMID- 16898595
TI  - [Clinical experience with intravesical instillations of 5-aminolevulinic acid (5
      ALA) for the photodynamic diagnosis using fluorescence cystoscopy for bladder
      cancer].
AB  - PURPOSE: To report our clinical experience with intravesical instillations of 5
      aminolevulinic acid (5-ALA) for the photodynamic diagnosis of bladder cancer and
      to assess any side-effects of the diagnostic method. MATERIALS AND METHODS:
      Photodynamic diagnosis was performed in 18 patients of which 14 were men and 4
      women with a median age of 71 years (range 44-84), 7 were primary cases and 11
      were recurrent cases with bladder cancer. Two to two and half hours prior to
      endoscopy 1.5 g 5-ALA dissolved in 50 ml of 8.4% sodium hydrogen carbonate
      (NaHCO3) solution was instilled intravesically. For fluorescence excitation a
      blue light source (D-LIGHT System, Karl Storz Endoscopy Japan K. K.) was used.
      Under white and fluorescence light guidance, tumor locations were recorded, cold
      cup biopsies were taken and tumors were resected. The levels in images of the 5
      aminolevulinic acid-induced fluorescence were compared with the pathological
      results. The area under the receiver operative characteristic (ROC) curve (AUC)
      in blue light endoscopy was also compared with that in white light endoscopy.
      RESULTS: Among the 129 specimens obtained by transurethral biopsy 45 were
      obtained from polypoid lesion and 84 from non-polypoid lesion, and among the 76
      malignant diseases 36 were obtained from polypoid lesion and 40 from non-polypoid
      lesion (including 19 carcinoma in situ), and 21 patients with dysplasia were
      detected pathologically, with a sensitivity of 89.5% and specificity of 58.5%
      with a predictive accuracy of 77.0%. The AUC in blue light endoscopy was more
      than that in white light endoscopy in not only all cases (p = 0.010) but also in
      cases with non-polypoid lesion (p = 0.007) and recurrent cases (p = 0.002).
      Duration of 5-ALA instillation with a median time of 80 (range 30-150) min. did
      not seem to affect the accuracy of photodynamic diagnosis. Procedures were well
      tolerated by all patients with mild bladder irritability but no systemic side
      effect. CONCLUSION: Photodynamic diagnosis with intravesically applied 5-ALA is
      more effective than observation by conventional cystoscopy in detecting bladder
      cancer without additional risk or complication, and is expected to become a
      golden standard in the detection program.

PMID- 16898596
TI  - [Yoke technique for severe proximal hypospadias].
AB  - PROPOSED: Various techniques have so far been reported for the repair of
      hypospadias, however, a one-stage procedure for the repair of severe proximal
      hypospadias still remains difficult to perform. We recently have begun to use the
      Yoke hypospadias repair technique for the treatment of severe proximal
      hypospadias. PATIENTS AND METHODS: As the chief surgeon, I performed a one-stage
      hypospadias repair on 40 proximal hypospadiac patients with severe fibrous
      chordee between July 1992 and December 2004. During the early period, eleven
      patients underwent urethroplasty by the Transverse Preputial Island Flap
      techinique (TPIF). Next, 10 patients underwent One-stage Urethroplasty with
      Parameatal Foreskin flap technique (OUPF IV). Finally, the most recent 19 had
      their hypospadias repaired by the Yoke technique. RESULTS: With the TPIF
      technique in the early periods, only 6 out of 11 patients underwent a successful
      repair (54.5%). With the OUPF IV technique, the success rate was only 60.0% (6
      out of 10 cases). In contrast, 17 out of 19 cases treated by the Yoke technique
      in the most recent period had a successful repair, although proximal
      urethrocutaneous fistula and urethral stenosis occurred in one patient,
      respectively. A relatively high success rate was therefore obtained using the
      Yoke technique for the repair of severe proximal hypospadias. CONCLUSION: The
      Yoke techniques for the repair of hypospadias is therefore considered to be a
      safe and effective technique for the repair of proximal hypospadias because of
      the continuous skin flap of the ventral urethral plate and the prepuce with a
      blood supply from the circumferential vascular pedicle. We consider this
      technique to be very useful for the treatment of severe proximal hypospadias.

PMID- 16898597
TI  - [Laparoscopic pyeloplasty for ureteropelvic junction obstruction].
AB  - PURPOSE: We performed laparoscopic pyeloplasty in 11 patients with ureteropelvic
      junction (UPJ) obstruction and evaluated the clinical outcomes of this surgery.
      MATERIALS AND METHODS: Between August 2001 and February 2004, 11 patients with
      UPJ obstruction underwent laparoscopic pyeloplasty in our institute. In all
      patients, symptoms were presented and UPJ obstruction was confirmed by
      radiographic examinations. Ten patients had primary obstruction, while one
      patient had secondary obstruction. Retroperitoneal approach was applied in all
      but one patient who needed intraperitoneal approach due to secondary obstruction.
      We performed Anderson-Hynes dismembered pyeloplasty, Hellstrom technique and
      Fenger plasty in 8, 2 and 1 patient, respectively. Nephropexy was performed in 2
      patients with nephroptosis, and isthmusectomy was performed in 1 patient with
      horseshoe kidney, simultaneously. RESULTS: The mean operative time was 312
      minutes (210-371) and the mean blood loss (including urine) was 75 ml. No blood
      transfusion was required, and all procedures were performed safely. Crossing
      vessels were found in 5 patients (45%). Pyelonephritis was the only postoperative
      complication, managed by the administration of antibiotics. Symptoms were
      disappeared without recurrences in all patients at mean follow up time of 18
      months (6-36). ( CONCLUSION: Although the number of cases was small with
      relatively short follow up period, the clinical outcomes of laparoscopic
      pyeloplasty in our institute were almost satisfied, as previously reported by
      other investigators. Laparoscopic pyeloplasty might be one of the standard
      treatments for patients with UPJ obstruction, although we should carefully
      consider about indication, approach and operation method.

PMID- 16898598
TI  - [Clinical study of bladder tamponade resulting from clots of blood].
AB  - PURPOSE: There were many case reports about bladder tamponade resulting from
      clots of blood. However, there were few reports about the clinical study that
      result from collecting cases of bladder tamponade. Thus, we performed a
      retrospective study about bladder tamponade resulting from clots of blood that we
      had managed. MATERIAL AND METHODS: We investigated 20 patients who had bladder
      tamponade and were consulted at our facility between October 2002 and September
      2005. We researched causes of the bleeding, characteristics of the patients, the
      laboratory data of coagulation system and treatments of our experience in
      managing patients. There were 17 males and 3 females. The average age of the
      patients was 74.0 years old. RESULTS: 8 cases took anticoagulant drugs, 6 cases
      had medical history of cerebral infarction or cardiac infarction, 4 cases took
      anticholinergic drugs and 9 cases had benign prostate hypertrophy or urethral
      stricture. Bleeding was due to bladder tumor in 9, prostate cancer in 1,
      radiation cystitis in 3, chronic cystitis in 1, malignant lymphoma in 1,
      idiopathic causes in 3 and unknown causes in 2 cases. Except 1 case, in all
      cases, evacuation of the clots was the first procedure followed by saline
      irrigation. This initial line of treatment was able to control the hemorrhage in
      40% of the patients. For the remaining cases, transurethral coagulation and
      resection of bladder tumor were used as the second line treatment, and
      furthermore, radical cystectomy was performed in 1 case. Surgical treatments were
      required in 12 cases. Blood transfusion was required in 4 cases. CONCLUSION:
      According to progress aging society, the amounts of taken anticoagulant drugs and
      the patients who had lower urinary tract dysfunction may increase. It may be
      suggested that the cases of bladder tamponade resulting from clots of blood
      without bladder tumor or radiation cystitis tend to increase.

PMID- 16898599
TI  - [Cranial nerve palsies due to skull base metastases in patients with prostate
      cancer: a report of two cases].
AB  - Two patients with prostate cancer showed cranial nerve palsies due to skull base
      metastases. Case 1: A 64-year-old man had prostate cancer (T4 N0 M1, Gleason
      score 7, prostate-specific antigen [PSA] level 372 ng/mL) with multiple bone
      metastases. Seventy-seven months after initiation of therapy, he had an
      articulation disorder and palsy of the left side of the tongue, with 12th cranial
      nerve palsy. Case 2: A 75-year-old man had a prostate cancer (T3b N0 M1, Gleason
      score 7, PSA level 177 ng/mL) with multiple bone metastases. Sixty-six months
      after initiation of therapy, he had hearing loss, noise in the right ear, and
      dizziness, with 8th cranial nerve deficits. Magnetic resonance imaging showed low
      intensity in the clivus in both cases, and all over the skull in case 2. The
      first patient was treated with radiation therapy and intravenous steroids at an
      early date. His symptoms improved.

PMID- 16898600
TI  - [Bilateral uretero-common iliac arterial fistula with long term uretelal stent: a
      case report].
AB  - A 37-year-old man underwent Miles' operation and adjuvant irradiation therapy for
      rectum cancer in 1999. The patient suffered from bilateral ureteral stricture
      after the previous therapies. Bilateral double-J ureteral stents were inserted
      and exchanged at regular intervals. Four years after the start of ureteral
      stenting, he complicated with gross hematuria and dysuria. When the right double
      J stent was exchanged, massive bleeding from external opening of urethra was
      observed. Retrograde pyelography showed right uretero-iliac arterial fistula.
      Since endovascular treatment with covered stents had failed, we performed right
      common iliac artery embolization and femoral-femoral artery bypass. Two days
      after the operation, gross hematuria developed again. When the left ureteral
      stent was exchanged, active bleeding from the external meatus of urethra was
      revealed. Angiography showed extravasation from left common iliac artery. We
      diagnosed left uretero-iliac arterial fistula. Although we tried endovascular
      treatment with covered stent that was made of artificial vessel graft and
      metallic stent, thromboembolism was occurred in the covered stent. Finally, right
      axillo-femoral artery bypass was indicated. The last treatment achieved long-term
      good control of uretero-arterial fistula. The present case shows that uretero
      arterial fistula is a serious complication of long-term ureteral stenting,
      especially in the case of post pelvic surgery and irradiation.

PMID- 16898601
TI  - [Operative position suitable for transvaginal excision of urethral diverticulum
      or closure of urethrovaginal fistula].
AB  - Among the various surgeries in female urology, transvaginal excision of urethral
      diverticulum needs careful and meticulous procedures in order to avoid some
      operative complications, such as urethral stricture or urethrovaginal fistula. In
      the present report, we present a woman with urethral diverticulum who initially
      underwent transvaginal excision of diverticulum in the dorsal lithotomy position,
      but she was complicated with urethrovaginal fistula postoperatively.
      Unfortunately, we failed to repair her fistula when she underwent excision of the
      fistula in the dorsal lithotomy position. With reconsideration of an operative
      position useful for transvaginal surgery, we succeeded in fistula closure in the
      Jackknife prone reverse-lithotomy position, and thereafter, two subsequent
      patients with urethral diverticulum were successfully treated with transvaginal
      excision of diverticulum in this operative position. In the transvaginal approach
      to the peri-urethral disorders, the Jackknife prone reverse-lithotomy position
      was notably superior to the dorsal lithotomy position with the following
      advantages: (1) the surgeons can easily operate in a bright and large surgical
      site without any blind view. (2) the surgeons can dissect and suture safely and
      accurately. (3) the assistants also can help in the operation bimanually in the
      same view as the surgeon when the posterior vaginal wall is fixed with a
      retractor.

PMID- 16898602
TI  - [Brain-gut interactions].

PMID- 16898603
TI  - [Introduction: Irritable bowel syndrome].
AB  - Patients with irritable bowel syndrome (IBS) suffer from embarrassing symptoms of
      abdominal pain/discomfort associated with altered bowel movement, sometimes with
      urgency. Routine clinical examination is not able to identify the origin of
      symptoms, which may lead to the physicians to doubt the symptoms patients
      complain of. As a consequence, patients may mistrust such physicians. Diagnosis
      of IBS deeply depend on the subjective symptoms and judgment of the patients,
      without any objective parameter to show any abnormalities. Also, any diagnostic
      criteria is not perfect yet. Furthermore, we do not have any potent therapeutic
      approach yet. Therefore, we should establish good patient-physician relationship
      at the beginning of the approach to IBS patients.

PMID- 16898604
TI  - [Disease concept and definition of irritable bowel syndrome].
AB  - Irritable bowel syndrome (IBS) is a disease entity characterized by recurrent
      abdominal pain or discomfort associated with altered bowel movement, in which no
      obvious pathogenetic lesion is identified to explain the symptoms. Postulated
      pathogenesis for IBS are; motility disorder, visceral sensation abnormalities,
      complex relationship between brain and gut, relationship to personality, and post
      infectious abnormalities in the colonic mucosa. Though many possibilities are
      presented, diagnostic criteria for IBS are entirely based on the subjective
      symptoms of the patients. Stress or psychological distress seem to play some
      roles in the pathogenesis, any of the diagnostic criteria for IBS do not include
      such aspects. Manning's criteria seem to be the first one to mention the
      diagnostic criteria. Rome consensus (1988) provoked the attention to IBS among
      the investigators, with followers like Rome II (1999), and BMW(2000) in Japan.
      Recently, Rome III criteria was published, which is more clinical oriented.

PMID- 16898605
TI  - [Epidemiological studies in irritable bowel syndrome].
AB  - Irritable bowel syndrome (IBS) has gradually been understood from recent
      epidemiological studies. Overall prevalence of IBS varies between 5% and 20%.
      Constipation-predominant IBS is more common in women. IBS patients are more
      likely to show nongastrointestinal symptoms (somatization) and illness behaviors,
      especially in women. IBS patients have poor health-related quality of life.
      Although small numbers of subjects with IBS in the community visit physicians,
      socioeconomic impact caused by this disorder is not ignored in terms of direct
      health care costs and indirect effects including work absenteeism. It should be
      necessary to know these diverse aspects of such 'difficult' patients with IBS
      considering a bio- psycho- social model in clinical practice.

PMID- 16898607
TI  - [BMW diagnostic criteria for IBS].
AB  - Rome I diagnostic criteria for IBS was published in 1992 and it became a global
      diagnostic criteria. However, the criteria was not practical and somewhat
      complicated. Moreover, its symptomatic duration was too long (defined as more
      than 3 months) to be introduced in clinical practice. Therefore, Japanese member
      of BMW(Bowel Motility Workshop) tried to develop a new diagnostic criteria for
      IBS and it was established in 1995 by way of the Delphi method. The criteria was
      named as BMW diagnostic criteria and it was shown below: BMW diagnostic criteria
      for IBS (1995) At least one month or more of repetitive symptoms of the following
      1) and 2) and no evidence of organic disease that likely to explain the symptoms.
      1) Existence of abdominal pain, abdominal discomfort or abdominal distension 2)
      Existence of abnormal bowel movement (diarrhea, constipation) Abnormal bowel
      movement includes at least one of the below; (1) Abnormal stool frequency (2)
      Abnormal stool form (lumpy/hard or loose/wartery stool) Moreover, the following
      test should be performed as a rule to exclude organic diseases. (1) Urinalysis,
      fecal occult blood testing, CBC, chemistry (2) Barium enema or colonofiberscopic
      examination The other diagnostic criteria for IBS was also reviewed and their
      characteristics were compared with BMW diagnostic criteria.

PMID- 16898606
TI  - [Use of Rome III criteria for diagnosing irritable bowel syndrome].
AB  - Irritable bowel syndrome (IBS) is one of the most common functional
      gastrointestinal disorders(FGIDs) characterized by chronic abdominal pain or
      discomfort, which is associated with changes in stool frequency and/or form. Rome
      II criteria for IBS was used widely in research and practice. Besides, Rome III
      criteria was recently published. Because IBS is a frequent disease, the spread of
      Rome III criteria will play an important role of pathophysiological study and new
      therapy in gastrointestinal medical care.

PMID- 16898608
TI  - [Post infectious irritable bowel syndrome experimental model].
AB  - Irritable bowel syndrome may be consisted of several subsets of functional
      disorders including a subset of post inflammatory and post infectious disorders.
      Animal models revealed prolonged hyper-kinesis of the intestinal muscle and
      visceral hyperalgesia in adult mice previously received phychological stress or
      bowel irritation in neonatal period. Murine infectious experiment reproduced
      adult post infectious functional disorders. Involvement of acute phase Th2
      cytokine production and prolonged TGFbeta1 production contribute to intestinal
      hyper-kinesis in post nematode infectious rat model. Pathogenesis of irritable
      bowel syndrome may be further subdivided by the results of experimental models,
      and a novel therapeutic approach is expected from such experimental models.

PMID- 16898609
TI  - [The gastrointestinal motor function in irritable bowel syndrome (IBS)].
AB  - Irritable bowel syndrome (IBS) is presumed to be a gastrointestinal motility
      disorder with the brain-gut interaction. Psychological stress and stimuli of the
      colonic lumen increase colonic motor function which is exaggerated in IBS
      patients. Corticotropin-releasing hormone (CRH) is considered to be a major
      mediator of stress responses in the brain-gut interaction. Similarly, peripheral
      administration of CRH affects colonic motility, induces abdominal symptoms and
      stimulates ACTH secretion, all of which are exaggerated in IBS patients. CRH
      antagonist blocks the greater responses of colonic motility in IBS. CRH is a key
      peptide in the pathophysiology of IBS with the brain-gut interaction.

PMID- 16898610
TI  - [Visceral hypersensitivity].
AB  - Colorectal hyperalgesia has been supposed to be one of the key pathophysiological
      roles in irritable bowel syndrome (IBS). Recent animal models have demonstrated
      that neonatal maternal deprivation (stress memory) or repetitive rectal
      distension (pain memory) in neonatal animal triggers long-term hypersensitivity
      to rectal distension, indicating that negative events including abuse or maternal
      separation in childhood may play a crucial role on development of IBS. Several
      molecules such as corticotropin-releasing factor, serotonin, nerve growth factor,
      myosin light chain kinase, chemical mediators from mast cell, substance P and
      calcitonin gene-related peptide released from transient receptor potential
      vanilloid receptor 1 (TRPV1)-positive primary afferent nerves have been proved to
      induce visceral hyperalgesia. Novel drugs based on these findings have been
      developed.

PMID- 16898611
TI  - [Pathophysiology of irritable bowel syndrome].
AB  - Irritable bowel syndrome (IBS) is considered a biopsychosocial disorder resulting
      from a combination of 3 interacting mechanisms: psychosocial factors, altered
      motility and transit, which may reflect severity of bowel dysfunction, and
      increased sensitivity of the intestine or colon. In other words, mechanism in IBS
      is biopsychosocial disorders; psychosocial factors, altered motility, and
      heightened sensory function. Understanding the brain-gut axis is the key to the
      eventual development of effective therapies for IBS.

PMID- 16898612
TI  - [Tests to detect GI motility disorders and GI sensation in irritable bowel
      syndrome].
AB  - To evaluate the pathophysiology of irritable bowel syndrome, we have to know how
      to examine gut motility and visceral sensation. Examination for gastrointestinal
      (GI) motility disorders and abnormality of viscerosensory sensation originated
      from GI tract to the brain should be performed to evaluate pathophysiology of
      irritable bowel syndrome. GI dysmotility is detected by intraluminal pressure
      recording, and abnormality of GI sensation could be detected by barostat method.
      Recent advance is showing that functional MRI imaging may have a big impact on
      clarification of the pathophysiology of irritable bowel syndrome.

PMID- 16898613
TI  - [Ultrasonographic assessment of sigmoid colon in patients with irritable bowel
      syndrome].
AB  - Although the pathophysiological factors may play a role in the pathogenesis of
      irritable bowel syndrome (IBS), the function of sigmoid colon has been reported
      as a major pathogenesis of IBS. Our objective was to evaluate motility patterns
      of sigmoid colon by using ultrasonography(US) in patients with IBS compared to
      healthy volunteers (HV). SUBIECTS AND METHODS: <Fasting phase> US examination of
      sigmoid colon was performed in 69 patients with IBS and 69 HV with 3.75 MHz
      curved array scanner and 7.5 MHz linear array scanner. The US probe was
      positioned longitudinally to permit simultaneous visualization of sigmoid colon
      crossing over the iliopsoas. We classified 3 types of fasting sigmoid colon,
      spastic type, empty type, and normal type, according to the US findings.
      <Postprandial phase> Four IBS patients with diarrhea, 4 with constipation and 4
      HV were given the liquid test meal (200ml, 400kcal). The frequency of segmental
      contractions (contractions without propagation) and propulsion were evaluated by
      US in the same fashion for 30 minutes before and for 60 minutes after
      investigation. RESULTS: <Fasting phase> Sixty-two percent of IBS showed spastic
      type and 65% of HV showed normal type. IBS patients accounted for 80 % of spastic
      type (IBS vs spastic type of US findings: Sensitivity 62%, Specificity 91%).
      <Postprandial phase> The changes of frequency of segmental contractions were
      smaller in IBS patients with constipation. The changes of frequency of propulsion
      were larger in IBS patients with diarrhea. CONCLUSION: Ultrasonographic
      assessment of sigmoid colon may provide a better understanding of the
      pathogenesis of IBS.

PMID- 16898614
TI  - [Barostat procedures].
AB  - Barostat is equipment for studying smooth muscle tone and sensory thresholds in
      the gastrointestinal (GI) tract. The principle of it is to maintain a constant
      pressure within an air-filled bag positioned in the lumen of the GI tract to be
      studied. Patients with irritable bowel syndrome (IBS) have been shown to have
      lower pain thresholds by barostat. Barostat would be one of the key procedures
      for studying pathophysiology in patients with IBS, although this method should be
      further standardized.

PMID- 16898615
TI  - [Psychological symptoms in IBS].
AB  - Patients with irritable bowel syndrome (IBS) have chronic abdominal symptoms and
      their health perceptions are impaired though the causes of their symptoms are not
      explained by routine examinations. IBS patients often show psychological symptoms
      represented by anxiety and depression, and many of them have the complication of
      anxiety disorder including panic disorder, depressive disorder, PTSD and so on.
      In our experience, 27% of IBS patients have the co-morbidity of panic disorder,
      and these two disorders exacerbated symptoms each other. Such condition impairs
      health-related quality of life in IBS patients. Psychological and behavioral
      therapy may benefit in symptomatic relief in IBS patients, suggesting strong
      participation of phsycological aspects in IBS patients.

PMID- 16898616
TI  - [Review: treatment of irritable bowel syndrome based upon a Japanese guideline].
AB  - Irritable bowel syndrome (IBS) is defined as abdominal pain and discomfort with
      altered bowel habits in the absence of any organic disorder. More than 10% of
      general population are considered to be affected by IBS. A guideline on its
      diagnosis and treatment has been issued in Japan in 2002. Accordingly, the
      therapeutic approach of IBS will be reviewed here. The most important issue of
      treatment is the establishment of a good physician-patient relationship. Given
      the limited efficacy of pharmacologic therapy and known psychological factors
      involved, effective treatment of IBS requires a comprehensive, multifaceted
      approach.

PMID- 16898617
TI  - [Effect of polycarbophil Ca on IBS].
AB  - In this chapter, I mentioned the effect of polycarbophil Ca on IBS. IBS is
      classified into 3 types; diarrhea type, constipation type and combined type.
      Polycarbophil Ca is effective for all types of IBS.

PMID- 16898618
TI  - [Antagonists of the type 3 serotonin receptor (5 -HT3) in IBS].
AB  - Irritable bowel syndrome (IBS) is a common chronic gastrointestinal (GI)
      disorder, but its pathophysiology remains unknown. 5-hydroxytryptamine (5-HT,
      serotonin) is an important neurotransmitter involved in the brain-gut connection.
      Alosetron, a 5-HT3 receptor antagonist, has been demonstrated in randomized,
      placebo-controlled trials (RCT) to be effective in diarrhea-predominant IBS(IBS
      D). Constipation is the most common adverse event. Alosetron improved abdominal
      pain and discomfort and stool consistency in both female and male patients, but
      it did not improve other symptoms (sense of urgency, stool frequency and
      bloating) in male patients. Although less is known about the gender differences
      in therapeutic benefit, a new 5-HT3 antagonist, cilansetron, has demonstrated
      effectiveness in male and female IBS-D patients and is currently under clinical
      trials.

PMID- 16898620
TI  - [Treatment for irritable bowel syndrome--psychotropic drugs, antidepressants and
      so on].
AB  - Irritable bowel syndrome (IBS) is a functional disease with good prognosis, which
      is diagnosed by exclusion of possible causative organic diseases. However, since
      the patients tend to have strong psychotic symptoms including anxiety, tension,
      depression, irritation and insomnia, this syndrome has to be elucidated as a
      psychosomatic disease. Although the symptoms are usually limited to
      gastrointestinal symptoms such as abdominal pain and abnormal bowel movements,
      many patients also manifest some kinds of psychiatric abnormalities such as
      hypochondria, depression, hysteria, panic disorder and posttraumatic stress
      disorder. Especially, the prevalence of depression is high. Therefore, use of
      psychotropic drugs is efficient in treating IBS. Antidepressant agents including
      tricyclic agents such as amitriptyline, trimipramine, imipramine, clomipramine,
      amoxapine and nortriptyline; tetracyclic antidepressant; antidepressants such as
      SSRI and SNRI; sulpiride; benzodiazepine class anxiolytic agents; tandospirone;
      and Chinese herbal medicine are being used. IBS is a stress-related disease.
      Therefore, in spite of the importance of pharmacotherapy, patients should also be
      instructed to avoid the stress that aggravates the symptoms in all aspects of
      daily life.

PMID- 16898619
TI  - [Serotonin 5- HT4 receptor agonist (mosapride citrate)].
AB  - Irritable bowel syndrome is a functional gastrointestinal disorder characterized
      by abnormal sensation and motility in the lower gastrointestinal tract. In
      constipation-type irritable bowel syndrome, decreased bowel motility causes
      stagnation of feces and gas, resulting in enhanced pain sensation of the bowel.
      Mosapride citrate is a selective serotonin 5- HT4 receptor agonist and enhances
      propulsive activity throughout the gastrointestinal tract. Mosapride citrate was
      orally administered to 11 patients with constipation-type irritable bowel
      syndrome to investigate its effect on this disease. The result showed that
      mosapride citrate alleviated abdominal pain and abdominal distension, loosened
      stools, shortened bowel transit time, and decreased flatus in the bowel. The
      results suggest that mosapride citrate is useful for the treatment of irritable
      bowel syndrome.

PMID- 16898621
TI  - [Probiotics].
AB  - While the precise pathophysiology of IBS remains to be elucidated, dysmotility
      and altered visceral perception/sensation are currently the most popular
      hypotheses. More recently, roles for enteric infection and intestinal
      inflammation have been proposed. Probiotics, defined as live or attenuated
      bacteria or bacterial products that confer a significant health benefit to the
      host, have the potential to provide a clinical tool to explore these
      interactions. We reviewed the effects of probiotics on IBS symptoms.

PMID- 16898622
TI  - [Psychosomatic approach for IBS patients].
AB  - Psychosomatic medical treatment is not a treatment that only specialists can do.
      On psychosomatic approach for IBS patients, it is important to understand not
      only IBS symptoms but also IBS patients themselves and their psychosocial
      factors. Not a few serious IBS patients have aspects of anxiety and depression.
      It needs psychosomatic approach that combined with drugs and simple psychotherapy
      to treat them. In treating IBS patients, we should first consider not only
      organic or functional mechanism of their symptoms but also the psychosocial
      meaning of them.

PMID- 16898623
TI  - [Education to the patients of irritable bowel syndrome: diet and lifestyle
      advice].
AB  - Irritable bowel syndrome (IBS) is a functional gastrointestinal illness. In spite
      of its benign nature, we should pay much attention to IBS because of its huge
      negative impacts on 'quality of life', not only for mental or physical pain and
      medical expenses but also for significant social and job-related consequences.
      The treatment of IBS is based on the guidelines of the Ministry of Health, Labour
      and Welfare in Japan, with a proper physician-patient rapport. At the first step
      in these guidelines, physicians should advise IBS patients about their diet and
      lifestyle according to their main symptoms. It is also essential for the
      physicians to educate the patients properly, which relieves the symptoms in many
      cases without any cost involvement and untoward side effects.

PMID- 16898624
TI  - [Irritable bowel syndrome in the elderly].
AB  - Irritable bowel syndrome (IBS) is a very common gastrointestinal disorder. The
      prevalence of IBS is about 10-15% of the general population. Epidemiological
      studies suggested that the prevalence of IBS decreased with age, but IBS remains
      an important gastrointestinal illness in the aged. But there has been very few
      research examining on IBS in elderly. Whether advancing age impacts on IBS is
      largely unknown and how the disorder manifest in the elderly remains unclear.
      Aging is connected with an increasing prevalence of many chronic neurological
      difficulties, cardiovascular diseases and mental disabilities. The management of
      the IBS needs to take the age-related issues into account in elderly. Clinical
      therapeutic trials should be undertaken in elderly people to ascertain treatment.

PMID- 16898625
TI  - [Irritable bowel syndrome in children].
AB  - Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder
      that affects children and adolescents. The recent development of the Rome
      diagnostic criteria and brain-gut pathways have greatly advanced the field. The
      child with IBS is best evaluated and treated in the context of a biopsychosocial
      model of care to relive symptoms and disability. Additional research is needed to
      develop drugs to modulate abnormalities in sensorimotor function of the enteric
      nervous system in IBS and relive specific symptoms and to assess the proper role
      of these drugs in the treatment of children and adolescents.

PMID- 16898626
TI  - [Depression in patients of irritable bowel syndrome].
AB  - Irritable bowel syndrome (IBS) is a psychosomatic disorder which onset and course
      is affected by psychological factors. It is also said that IBS symptoms and
      psychiatric symptoms are strongly related. In some reports, 29% of IBS patients
      consulting doctors were also diagnosed with major depression. There are also
      records that the consolidation of depression, panic disorder, and neurosis
      contributes to poor outcomes in serious cases of IBS. In this report, we have
      indicated the diagnosis and treatment of depression in primary care. For
      diagnosis, detailed medical interviews and use of psychological tests such as SDS
      or SRQ-D are recommended. Some types of anti-depressants are also effective for
      IBS symptoms as well as psychiatric problems. We suggest that treatment of
      psychological factors should also be considered when dealing with IBS.

PMID- 16898627
TI  - [Role of allergy in irritable bowel syndrome].
AB  - Preliminary studies have noted a possible association between IBS and allergic
      disorders. An increased prevalence of bronchial hyper-responsiveness in IBS has
      been reported. Moreover, foods are thought to often play a role in the diarrhea
      type IBS particularly in patients with atopic dermatitis. More than 50% of
      diarrhea type IBS patients have a history of allergies to some food and positive
      skin prick tests. Surveys indicate that as many as 20-30 % of adults have some
      problems to foods, however, careful studies have suggested a range from <1% to
      7.5%. A systematic review of the literature concluded that it is still unclear
      whether diet is a key factor in exacerbating IBS symptoms and whether dietary
      manipulation is a valid treatment. The further studies are needed to evaluate the
      association between IBS and allergic disorders.

PMID- 16898628
TI  - [Brain function in IBS patients].
AB  - Irritable bowel syndrome(IBS) is functional disorder that is characterized by
      abdominal pain and changes in stool habits, and possibly related to abnormal
      brain-gut communication. Recent studies using brain imaging suggest the brain
      functions of IBS patients may be possibly different from that of control. We, in
      this article, review the recent knowledge regarding this point.

PMID- 16898629
TI  - [Quality of life in irritable bowel syndrome].
AB  - Irritable bowel syndrome (IBS) is a chronic disorder of unknown origin, which is
      a very common disease and a frequent complaint among patients consulting general
      practitioners or gastroenterologists. It is primary characterized by abdominal
      pain, alteration in bowel habit, abdominal discomfort that can significantly
      affect quality of life (QOL). Measurements of QOL in IBS patients are more
      complete than a symptomatic score for the evaluation of patient status, which
      would increase to use as the assessment of therapeutic effects.

PMID- 16898630
TI  - [Post-infectious IBS].
AB  - Irritable bowel syndrome (IBS) is a mulitifactorial disease. Bacterial
      gastroenteritis has been known as a risk factor of IBS. Current evidence shows a
      strong association between colonic infection and inflammation with development of
      IBS.

PMID- 16898631
TI  - [Effects of gender on irritable bowel syndrome].
AB  - Irritable bowel syndrome (IBS) is one of the most common functional bowel
      disorders, with prevalence between 10% and 15%, which predominates in female. Two
      thirds of IBS patients are female, and the prevalence of condition range from 14%
      to 24%. In addition to sex hormone, the other factors, i.e.) visceral perception,
      autonomic nervous system and pharmacological treatment response, are associated
      with gender differences in IBS. Recent studies indicate that pain thresholds to
      visceral stimulation are lower in females with IBS compared with males with IBS.
      It is also indicated that males with IBS have greater sympathovagal balance in
      response to visceral stimulation. Further elucidation of gender differences in
      IBS may contribute to treatment of IBS.

PMID- 16898632
TI  - [Primary care in pediatrics. 5. Benign and life-threatening convulsions].

PMID- 16898633
TI  - [Therapeutic strategy to promote regeneration of the injured central nervous
      system].
AB  - Spontaneous regeneration of lesioned fibers is limited in the adult central
      nervous system due to an unfavorable environment. Several myelin-derived proteins
      have been identified to inhibit neurite outgrowth in vitro. These proteins induce
      activation of Rho in some neurons. Inhibition of Rho or Rho-kinase, downstream
      effector of Rho, promotes axon regeneration in vivo. Recent reports suggest that
      several other proteins are axon growth inhibitors. Therapeutic strategy to block
      the multiple axon growth inhibitors may provide efficient tools that produce
      functional regeneration following injuries to the central nervous system. In
      addition, it is noted that synaptic plasticity in pre-existing pathways and the
      formation of new circuits through collateral sprouting of lesioned and unlesioned
      fibers are important components of the recovery process.

PMID- 16898634
TI  - [Development of therapeutic strategies based on immunology against tumors].

PMID- 16898635
TI  - [Reverse genetics for measles virus].

PMID- 16898636
TI  - The extramedullary guide of the proximal tibia resection should be seen straight
      in front during total knee arthroplasty.
AB  - If surgeons see the shaft of the extramedullary guide from lateral to the guide
      during preparation of the proximal tibia resection during total knee
      arthroplasty, the tibial component may be implanted in varus position in the
      frontal plane. In order to clarify the effect of the angle of the surgeons' sight
      relative to the sagittal plane and the posterior slope angle of the resected
      surface on varus position of the tibial component in the frontal plane,
      mathematical analysis was performed. Three-dimensional coordinate system was
      utilized so that the central axis of the tibial shaft on the Z-axis and the shaft
      of the guide were skew. The relationship between two lines was analyzed solving
      equations on three dimensional planes. When the posterior slope angle is 10
      degrees, and if surgeons see the shaft of the guide 10 degrees, 20 degrees and 30
      degrees lateral to the sagittal plane, and the shaft and the central axis of the
      tibial shaft would seem to be parallel, the true varus tilt angle of the shaft on
      the frontal plane is 1.8 degrees, 3.7 degrees and 5.8 degrees, respectively. The
      extramedullary guide should be seen straight in front of the guide.

PMID- 16898637
TI  - Development of Japan's open heart surgery from 1952 to 1956.

PMID- 16898638
TI  - Easier node dissection after chemoradiotherapy for lung cancer with collagen
      insertion at mediastinoscopy.
AB  - OBJECTIVE: Induction chemoradiotherapy followed by anatomical resection is a
      current therapeutic strategy for non-small-cell lung cancer with mediastinal node
      involvement. Dense peritracheal fibrosis and sclerosis after chemoradiotherapy
      cause difficult mediastinal node dissection. We evaluated a novel technique to
      make the mediastinal node dissection easier after induction therapy. METHODS: At
      the end of mediastinoscopic node biopsy for staging of lung cancer, cotton-type
      collagen was inserted anterior and lateral to the trachea in patients with
      pathologically confirmed mediastinal node involvement (n=45). The induction
      therapy consisted of concurrent use of platinum-based chemotherapy and
      hyperfractionated radiotherapy. After the chemoradiotherapy all patients
      underwent a pulmonary resection with complete mediastinal node dissection 7-12
      weeks after the collagen insertion. Surgical findings of the mediastinum and the
      time for node dissection were compared with those without collagen insertion at
      mediastinoscopy after chemoradiotherapy (n=5). RESULTS: All five patients without
      collagen insertion showed sclerotic and fibrotic change of mediastinal nodes with
      severe adhesion to the trachea. In 42 of 45 patients with collagen insertion
      (93.3%) the collagen remained unabsorbed and separated the mediastinal nodes from
      the trachea. Mediastinal node dissection was easily accomplished by removing
      mediastinal tissues lateral and anterior to the collagen. The rate of mediastinal
      node separation was significantly higher with collagen insertion than without
      (p<0.0001). The times for node dissection in patients with and without collagen
      insertion showed no significant difference. CONCLUSION: Cotton-type collagen
      insertion at staging mediastinoscopy for lung cancer separates the mediastinal
      nodes from the trachea and makes the node dissection easier after induction
      chemoradiotherapy.

PMID- 16898639
TI  - End-to-side anastomosis for coarctation of the aorta and type A aortic arch
      interruption with hypoplastic aortic arch.
AB  - OBJECTIVE: We investigated the advantages of reconstructing the aortic arch in
      neonates and infants by end-to-side anastomosis (ESA) in aortic coarctation and
      type A aortic arch interruption. SUBJECTS AND METHODS: The patients were 28
      neonates and infants who underwent median full sternotomy for correction of
      aortic coarctation (CoA) and type A interrupted aortic arch (IAA), at our
      institute, from October 1997 to September 2002. The cases were divided into two
      groups: ESA was performed in 16 cases (group A) and extended end to end
      anastomosis in 12 cases (group B). All repairs were made using simple clamping of
      the descending aorta under cardiac arrest. We compared groups A and B with regard
      to duration of simple clamping, postoperative blood pressure in the upper and
      lower extremities, echocardiographic pressure gradient, and the presence or
      absence of tracheal stenosis as diagnosed by postoperative clinical symptoms and
      chest radiography. RESULTS: No significant difference between the groups was
      found in age, gender, body weight, or the ratio of CoA to IAA. In addition, there
      was no difference between the two groups in the duration of simple clamping or
      the difference in blood pressure between the lower and upper extremities.
      However, the echocardiographic pressure gradient at the site of anastomosis in
      group A was significantly lower than that in group B. There were no cases with
      symptoms of bronchial stenosis in either group. CONCLUSION: ESA is a relatively
      simple method for treating CoA or IAA with hypoplastic aortic arch, and was found
      to be effective for the elimination of residual stenosis.

PMID- 16898641
TI  - Resection of a cardiac tumor extending into the inferior vena cava presenting as
      Budd-Chiari syndrome.
AB  - This report describes the successful treatment of a case of cardiac
      adenocarcinoma with the clinical presentation as Budd-Chiari syndrome. Complete
      surgical excision of the atriocaval mass was successfully achieved under deep
      hypothermic circulatory arrest. Histopathological diagnosis of this tumor was
      tubular adenocarcinoma with positive immunostaining by carcinoembrionic antigen.
      Subsequent systemic search could not detect any evidence of extra-cardiac primary
      site and distant metastatic lesion. A 2-year follow-up without any adjuvant
      therapy revealed no sign of recurrence.

PMID- 16898640
TI  - Effects of rabeprazole or famotidine during cardiac surgery on perioperative
      gastric and esophageal pH readings.
AB  - OBJECTIVES: Upper gastrointestinal bleeding, particularly from a stress-induced
      duodenal ulcer, is an extremely important perioperative complication in
      cardiovascular surgery. METHODS: In the present study, 33 patients undergoing
      elective open heart surgery between July 2000 and February 2001 were allocated to
      either a famotidine (FAM) or rabeprazole (RPZ) group to examine the perioperative
      gastric and esophageal pH readings, in conjunction with an investigation into the
      effect of infection with Helicobacter pylori (HP). RESULTS: Postoperative upper
      gastrointestinal bleeding did not occur in either group, and the intraoperative
      and postoperative mean gastric pH readings, as well as the holding time pH>6,
      suggested sufficient acid suppression by either drug. Gastric acid secretion was
      less strongly suppressed in HP-negative patients in the FAM group, but was
      unaffected by HP infection status in the RPZ group. CONCLUSION: The FAM group and
      RPZ group revealed a sufficient effect of gastric acid suppression. It was
      indicated that FAM had an insufficient effect of gastric acid suppression for HP
      negative patients.

PMID- 16898642
TI  - Intrapulmonary metastasis developing eighteen years after complete resection of
      thymoma.
AB  - We present a case of intrapulmonary metastasis developing 18 years after complete
      resection of thymoma. An 8 mm nodule in the lower lobe of the left lung was noted
      on chest X-ray in a 76-year-old woman who had undergone complete resection of
      Masaoka's stage II thymoma 18 years earlier. Since the nodule grew to 17 mm
      during a 2-year follow-up, wedge resection was performed. The lesion was
      histologically diagnosed as an intrapulmonary metastasis from thymoma. Extremely
      late recurrence after complete resection of thymoma is discussed.

PMID- 16898643
TI  - Pulmonary lymphoma of mucosa-associated lymphoid tissue type followed as a long
      standing indeterminate lesion in immunoglobulin M-type paraproteinemia.
AB  - An 82-year-old woman with monoclonal immunoglobulin (Ig) M-type paraproteinemia
      had a large opacity in the right lung field. The abnormal shadow on roentgenogram
      had persisted for more than 6 years since the initial diagnosis of
      paraproteinemia, which had been diagnosed as Waldenstrom's macroglobulinemia
      (WM). Computed tomography revealed the lesion as a pulmonary tumor which was
      finally diagnosed as a marginal zone B-cell lymphoma of mucosa-associated
      lymphoid tissue (MALT) after surgical removal. MALT lymphoma constitutes the
      majority of primary pulmonary lymphomas and is often associated with monoclonal
      IgM-type paraproteinemia as well as WM, a distinctive lymphoproliferative
      disorder. Pulmonary MALT lymphoma should frequently be suspected in case of an
      indeterminate pulmonary tumor with IgM-type paraproteinemia.

PMID- 16898644
TI  - Infective endocarditis with congenital heart disease.
AB  - From 1988 to 2005, seven patients were operated at our hospital because of
      infectious endocarditis (IE) with congenital heart disease (CHD). Underlying CHD
      included ventricular septal defect (VSD) in 4 (2 previous operations with
      residual region), atrial septal defect (ASD) in 2 and bicuspid aortic stenosis
      (AS) in 1. No cases had preventive antibiotic prophylaxis for dental procedures.
      We could confirm bacteria origin from blood culture in all cases, but two
      patients had operations without gaining control of the infection. VSD or ASD
      closure and valve surgery were performed in four patients. One patient had a VSD
      closure, two patients had valve surgery. There were no operative or hospital
      deaths and there were no recurrences of IE during the study period. We
      successfully treated IE with CHD by enough debridement of the infective focus of
      IE, and valve surgery. It is important for patients with CHD to have preventive
      antibiotic prophylaxis for dental procedures.

PMID- 16898645
TI  - Homemade endovascular treatment of postoperative aortobronchial fistulas.
AB  - Successful treatments of aortobronchial fistulas were achieved in two cases using
      a homemade endovascular stent graft. In one, a 75-year-old man was operated on
      for a distal arch aneurysm 11 years previously. In the other, a 73-year-old woman
      was operated on for a ruptured type B aortic dissection 2 months previously. In
      both cases, the chief complaint was repeated hemoptysis, and the communication
      between the aorta and the airway tract was at the distal anastomotic site in the
      descending aorta. To minimize risks associated with reoperation, endovascular
      stent grafting was selected electively. Postoperative courses were uneventful and
      there were no recurrences of hemoptysis.

PMID- 16898646
TI  - Obstruction of the left ventricular outflow tract due to pannus formation after
      the implantation of a carbomedics aortic valve.
AB  - Excessive pannus formation after implantation of a prosthetic valve is an
      infrequent but serious complication. A 69-year-old woman who had received a 19-mm
      CarboMedics aortic valve 11 years ago was readmitted to our hospital with dyspnea
      and chest oppression. Cineradiography did not show the restriction of valve
      movement. The aortic peak pressure gradient was calculated by Doppler
      echocardiography to be 104 mmHg. Based on the diagnosis of stenosis of the left
      ventricular outflow tract, the patient underwent reoperation. At reoperation, the
      pannus had formed circumferentially without disturbing the movement of the
      leaflet. A 19-mm St. Jude Medical Regent valve was implanted after enlargement of
      the aortic annulus. The patient's postoperative course was uneventful. We report
      this characteristic finding of pannus formation after the implantation of a
      CarboMedics valve in the aortic position.

PMID- 16898647
TI  - Primary pulmonary valve papillary fibroelastoma.
AB  - Papillary fibroelastoma (PFE) is a rare and benign cardiac tumor typically found
      on the valvular endocardium. In most cases, PFE is identified incidentally on
      echocardiography or during cardiac surgery. The patient was a 73-year-old man who
      had been treated for hepatocellular carcinoma for 5 years. On echocardiography, a
      2.5-cm diameter mass was detected in the pulmonary trunk just above the pulmonary
      valve. Through a transpulmonary arterial approach with cardiopulmonary bypass,
      the mass identified on the commissure of the right and posterior pulmonary cusp
      was surgically excised together with the attached endocardium. Despite the benign
      histology of PFE, lethal embolic events such as stroke, myocardial infarction,
      and pulmonary embolism are reported in some cases. To prevent such complications,
      tumor identification and surgical excision are essential.

PMID- 16898648
TI  - Gorham's disease complicated by chyloma of the chest wall.
AB  - Gorham's disease is a rare disorder characterized by a non-malignant
      proliferation of thin-walled lymphatic vessels that result in progressive bony
      destruction and often extend into the surrounding soft tissues. Chylothorax is a
      common complication in cases of mediastinal involvement. Here we report a case of
      a 22-year-old male with Gorham's syndrome complicated by chyloma of the chest
      wall, but without chylothorax. To our knowledge, this is the first report
      demonstrating an abnormality of the parietal pleura prior to the clinical
      development of the chylothorax.

PMID- 16898649
TI  - Extended parasternal approach for aortic and tricuspid valve surgery.
AB  - We report an extended parasternal approach to aortic and tricuspid valves used in
      a 31-year-old man. The patient presented with a deformed sternum and severe
      adhesion between the sternum and right ventricular outflow tract, caused by
      postoperative mediastinitis, which lasted for 4 years after a radical operation
      for tetralogy of Fallot during his childhood. The extended parasternal approach
      provided a safe and excellent exposure of both aortic and tricuspid valves
      without postoperative chest wall instability.

PMID- 16898650
TI  - Bacterial conjunctivitis in pediatrics and primary care.

PMID- 16898651
TI  - Universal design in engineering's future.

PMID- 16898652
TI  - Exciting work: now and in the past.

PMID- 16898653
TI  - Ethics and the FDA.

PMID- 16898655
TI  - Micro- and macrostructure of sleep EEG.

PMID- 16898654
TI  - Quantitative EEG assessment.

PMID- 16898656
TI  - Estimation of the cortical connectivity patterns during the intention of limb
      movements.

PMID- 16898657
TI  - Intraoperative Neurological monitoring. Continuous evoked potential signal
      extraction and analysis.

PMID- 16898659
TI  - Functional near-infrared spectroscopy.

PMID- 16898658
TI  - Integration of EEG/MEG with MRI and fMRI.

PMID- 16898660
TI  - Computer-assisted arthroplasty using bioengineered autografts.

PMID- 16898661
TI  - A viral envelope as a vehicle for tracer, drug, and gene delivery.

PMID- 16898662
TI  - A wavelet approach to detecting electrocautery noise in the ECG.

PMID- 16898663
TI  - Senior design capstone courses and ABET outcomes.

PMID- 16898664
TI  - Janie needs relevance.

PMID- 16898665
TI  - (Engineering contributions to the life sciences)(-1).

PMID- 16898666
TI  - Use of low-temperature scanning electron microscopy to compare and characterize
      three classes of snow cover.
AB  - This study, which uses low-temperature scanning electron microscopy (LTSEM),
      systematically sampled and characterized snow crystals that were collected from
      three unique classes of snow cover: prairie, taiga, and alpine. These classes,
      which were defined in previous field studies, result from exposure to unique
      climatic variables relating to wind, precipitation, and air temperature. Snow
      samples were taken at 10 cm depth intervals from the walls of freshly excavated
      snow pits. The depth of the snow pits for the prairie, taiga, and alpine covers
      were 28, 81, and 110 cm, respectively. Visual examination revealed that the
      prairie snow cover consisted of two distinct layers whereas the taiga and alpine
      covers had four distinct layers. Visual measurements were able to establish the
      range of crystal sizes that occurred in each layer, the temperature within the
      pit, and the snow density. The LTSEM observations revealed the detailed
      structures of the types of crystals that occurred in the snow covers, and
      documented the metamorphosis that transpired in the descending layers. Briefly,
      the top layers from two of the snow covers consisted of freshly fallen snow
      crystals that could be readily distinguished as plates and columns (prairie) or
      graupel (taiga). Alternatively, the top layer in the alpine cover consisted of
      older dendritic crystal fragments that had undergone early metamorphosis, that
      is, they had lost their sharp edges and had begun to show signs of joining or
      bonding with neighboring crystals. A unique layer, known as sun crust, was found
      in the prairie snow cover; however, successive samplings from all three snow
      covers showed similar stages of metamorphism that led to the formation of depth
      hoar crystals. These changes included the gradual development of large, three
      dimensional crystals having clearly defined flat faces, sharp edges, internal
      depressions, and facets. The study, which indicates that LTSEM can be used to
      enhance visual data by systematically characterizing snow crystals that are
      collected at remote locations, is important for understanding the physics of
      snowpacks and the metamorphosis that leads to potential avalanche situations. In
      addition, the metamorphosis of snow crystals must be considered when microwave
      radiometry is used to estimate the snow water equivalent in the winter snowpack,
      because large snow crystals more effectively scatter passive microwave radiation
      than small crystals.

PMID- 16898667
TI  - Resolution limit for electron beam-induced deposition on thick substrates.
AB  - Recently, the fabrication resolution in electron beam-induced deposition (EBID)
      has improved significantly. Dots with an average diameter of 1 nm have been made.
      These results were all obtained in transmission electron microscopes on thin
      samples. As one may think that such resolution can be achieved on thin samples
      only, it is the objective of this paper to show that this should also be possible
      on thick samples. For that purpose we use Monte Carlo simulations of the electron
      sample interaction and determine the surface area where secondary electrons are
      emitted. Assuming that these electrons cause the deposition in EBID, a comparison
      can be made between deposition on a thin and a thick sample. The Monte Carlo code
      we developed will be described and applied to the deposition induced by a 200 keV
      primary electron beam on an ultra-thin (10 nm) and a bulk-like (1,000 nm) Cu
      sample. Near the point of incidence of the primary beam, the deposit size is
      independent of the substrate thickness, such that a 1-nm resolution should be
      possible to achieve on a thick substrate as well. Thicker substrates only affect
      the tails of the deposit distribution which contain more mass than thin substrate
      deposit tails.

PMID- 16898668
TI  - A model of the deciliation process caused by Mycoplasma fermentans strain
      incognitus on respiratory epithelium.
AB  - The aim of this study was to investigate by light microscopy as well as by
      scanning and transmission electron microscopy the deciliation process which takes
      place on the respiratory epithelium of tracheal explants after experimental
      infection with Mycoplasma fermentans strain incognitus. Time-point photography
      allowed distinguishing five phases which occurred during the infection on the
      epithelial cell surface: (1) Attachment of M. fermentans to the cilia causing
      clumping of the cilia tips; (2) matting of cilia into bundles; (3) formation of
      abnormally shaped and shorter cilia; (4) collapse of cilia onto the epithelial
      cell surface; and (5) widespread loss of cilia. Based on the photographic images,
      a schematic model of the deciliation process was developed. Various potential
      factors contributing to the cilia destruction are discussed, including the
      release of mycoplasmal toxins, the physical presence of a high number of M.
      fermentans cells attached to the cilia, and the depletion of culture medium
      components by the mycoplasmas. This model of M. fermentans strain incognitus
      infection of respiratory epithelium is important for understanding mycoplasmal
      pathogenicity on a comparative level.

PMID- 16898669
TI  - Parameters and mechanisms governing image contrast in scanning electron
      microscopy of single-walled carbon nanotubes.
AB  - Image formation of single-walled carbon nanotubes (SWNTs) in the scanning
      electron microscope (SEM) is peculiarly sensitive to primary electron landing
      energy, imaging history, sample/substrate geometry, electrical conductivity,
      sample contamination, and substrate charging. This sensitivity is probably due to
      the extremely small interaction volume of the SWNTs' monolayered, nanoscale
      structures with the electron beam. Traditional electron beam/bulk specimen
      interaction models appear unable to explain the contrast behavior when directly
      applied to SWNTs. We present one systematic case study of SWNT SEM imaging with
      special attention to the above parameters and propose some physical explanations
      for the effect of each. We also demonstrate that it is possible to employ voltage
      biasing to counteract this extrinsic behavior, gain better control of the image
      contrast, and facilitate the interpretation of SWNT images in the SEM.

PMID- 16898670
TI  - The effect of colcemid and aluminum on the ultrastructure of human metaphase
      chromosomes.
AB  - Recently, we have reported new basic information on the ultrastructure of human
      metaphase chromosomes using both scanning and transmission electron microscopy.
      This includes the observation of a bipartite chromatid structure (BCS) for some
      metaphase chromatids, a "zipper-like" configuration (ZC) between chromatids that
      likely resulted from chromatin coiling, and a "brush-like" border (BB) that was
      observed primarily on chromosomes that were not exposed to colcemid. Now we have
      examined the effects of colcemid and several metals on the occurrence of the BCS,
      the ZC, and the BB. Although we do not as yet know the function of the zipper
      like and bipartite chromatid configurations, we have found that colcemid clearly
      caused a significant increase in the occurrence of chromosomes with a BCS or ZC.
      We also have confirmed our original observation of increased occurrence of the BB
      on chromosomes not exposed to colcemid and finally, have shown that aluminum and
      other metals had some effect on the frequencies of the BCS, the ZC, and the BB
      with and without exposure to colcemid.

PMID- 16898672
TI  - The morphology of the NiO-Al2O3 catalyst.
AB  - The morphology of the NiO-Al2O3 catalyst, prepared by coprecipitation,
      impregnation, and mechanical powder mixing with ca. 5, 10, and 20 wt% nickel
      treated at 400 degrees, 700 degrees, and 1100 degrees C, was studied. Scanning
      electron microscopy is a useful technique for determining the manner of catalyst
      preparation for particle size estimation of catalyst components, whereas their
      mutual interactions become visible in the obtained images.

PMID- 16898671
TI  - Scanning electron microscopic observations on micro-organisms in the root nodules
      of Tribulus terrestris L. (Zygophyllaceae).
AB  - Scanning electron microscopic observations were made on the micro-organisms of
      root nodules of Tribulus terrestris L. The results showed that nodules of T.
      terrestris contained dual infection consisting of Rhizobium sp. and Newmania
      karachiensis. Based on these observations, T. terrestris should be grouped with
      nonlegume Parasponia-type bacterial nodules.

PMID- 16898673
TI  - Smoking and the sudden infant death syndrome.
AB  - The aims of this review are (a) to critically examine the epidemiologic evidence
      for a possible association between smoking and the sudden infant death syndrome
      (SIDS), (b) to review the pathology and postulated physiological mechanism(s) by
      which smoking might be causally related to SIDS, and (c) to provide
      recommendations for SIDS prevention in relation to tobacco smoking. Over 60
      studies have examined the relation between maternal smoking during pregnancy and
      risk of SIDS. With regard to prone-sleep-position intervention programs, the
      pooled relative risk associated with maternal smoking was RR = 2.86 (95% CI =
      2.77, 2.95) before and RR = 3.93 (95% CI = 3.78, 4.08) after. Epidemiologically,
      to distinguish the effect of active maternal smoking during pregnancy from
      involuntary tobacco smoking by the infants of smoking mothers is difficult. Clear
      evidence for environmental tobacco smoke exposure can be obtained by examining
      the risk of SIDS from paternal smoking when the mother is a non-smoker. Seven
      such studies have been carried out. The pooled unadjusted RR was 1.49 (95% CI =
      1.25, 1.77). Consideration of the pathological and physiological effects of
      tobacco suggests that the predominant effect from maternal smoking comes from the
      in utero exposure of the fetus to tobacco smoke. Assuming a causal association
      between smoking and SIDS, about one-third of SIDS deaths might have been
      prevented if all fetuses had not been exposed to maternal smoking in utero.

PMID- 16898674
TI  - Involvement of environmental mercury and lead in the etiology of
      neurodegenerative diseases.
AB  - The incidence of neurodegenerative disease like Parkinson's disease and
      Alzheimer's disease (AD) increases dramatically with age; only a small percentage
      is directly related to familial forms. The etiology of the most abundant,
      sporadic forms is complex and multifactorial, involving both genetic and
      environmental factors. Several environmental pollutants have been associated with
      neurodegenerative disorders. The present article focuses on results obtained in
      experimental neurotoxicology studies that indicate a potential pathogenic role of
      lead and mercury in the development of neurodegenerative diseases. Both heavy
      metals have been shown to interfere with a multitude of intracellular targets,
      thereby contributing to several pathogenic processes typical of neurodegenerative
      disorders, including mitochondrial dysfunction, oxidative stress, deregulation of
      protein turnover, and brain inflammation. Exposure to heavy metals early in
      development can precondition the brain for developing a neurodegenerative disease
      later in life. Alternatively, heavy metals can exert their adverse effects
      through acute neurotoxicity or through slow accumulation during prolonged periods
      of life. The pro-oxidant effects of heavy metals can exacerbate the age-related
      increase in oxidative stress that is related to the decline of the antioxidant
      defense systems. Brain inflammatory reactions also generate oxidative stress.
      Chronic inflammation can contribute to the formation of the senile plaques that
      are typical for AD. In accord with this view, nonsteroidal anti-inflammatory
      drugs and antioxidants suppress early pathogenic processes leading to Alzheimer's
      disease, thus decreasing the risk of developing the disease. The effects of lead
      and mercury were also tested in aggregating brain-cell cultures of fetal rat
      telencephalon, a three-dimensional brain-cell culture system. The continuous
      application for 10 to 50 days of non-cytotoxic concentrations of heavy metals
      resulted in their accumulation in brain cells and the occurrence of delayed toxic
      effects. When applied at non-toxic concentrations, methylmercury, the most common
      environmental form of mercury, becomes neurotoxic under pro-oxidant conditions.
      Furthermore, lead and mercury induce glial cell reactivity, a hallmark of brain
      inflammation. Both mercury and lead increase the expression of the amyloid
      precursor protein; mercury also stimulates the formation of insoluble beta
      amyloid, which plays a crucial role in the pathogenesis of AD and causes
      oxidative stress and neurotoxicity in vitro. Taken together, a considerable body
      of evidence suggests that the heavy metals lead and mercury contribute to the
      etiology of neurodegenerative diseases and emphasizes the importance of taking
      preventive measures in this regard.

PMID- 16898676
TI  - Bioluminescent bacterial biosensors for the assessment of metal toxicity and
      bioavailability in soils.
AB  - A major factor governing the toxicity of heavy metals in soils is their
      bioavailability. Traditionally, sequential extraction procedures using different
      extractants followed by chemical analysis have been used for determining the
      biologically available fraction of metals in soils. Yet, the transfer of results
      obtained on non-biological systems to biological ones is certainly questionable.
      Therefore, bioluminescence-based bacterial biosensors have been developed using
      genetically engineered microorganisms, constructed by fusing transcriptionally
      active components of metal resistance mechanisms to lux genes from naturally
      bioluminescent bacteria like Vibrio fischeri for the assessment of metal toxicity
      and bioavailability in polluted soils. As compared to chemical methods, bacterial
      biosensors present certain advantages, such as selectivity, sensitivity,
      simplicity, and low cost. Despite certain inherent limitations, bacterial
      bioluminescent systems have proven their usefulness in soils under laboratory and
      field conditions. Finally, green fluorescent protein-based bacterial biosensors
      are also applicable for determining with high sensitivity the bioavailability of
      heavy metals in soil samples.

PMID- 16898675
TI  - Adverse health effects in humans exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin
      (TCDD).
AB  - The environmental contaminant 2,3,7,8-tetrachlordibenzo-p-dioxin (TCDD) belongs
      to the category of highly toxic, persistent organic pollutants that accumulate in
      animal fat and plant tissues. Today, background TCDD levels in human fat are
      showing a decreasing trend. The food chain is the main source of exposure in the
      human population. TCDD regulates the expression of a wide range of drug
      metabolizing enzymes and has an impact on a large number of biological systems.
      The most pronounced effects have occurred in occupational settings following the
      uncontrolled formation of TCDD after industrial accidents, as well as in rare
      intentional intoxications. Although the acute effects of TCDD exposure are well
      described in the literature, the long-term consequences have been underevaluated.
      The most well-known symptoms of severe acute intoxication are chloracne,
      porphyria, transient hepatotoxicity, and peripheral and central neurotoxicity.
      Because of the long-term persistence of TCDD in the human body, atherosclerosis,
      hypertension, diabetes, vascular ocular changes, and signs of neural system
      damage, including neuropsychological impairment, can be present several decades
      after massive exposure. Such chronic effects are nonspecific, multifactorial, and
      may be causally linked to TCDD only in heavily intoxicated subjects. This opinion
      is supported by the dose-dependent effect of TCDD found in exposed workers and by
      experimental animal studies.

PMID- 16898677
TI  - Dissolution of oxygen reduction electrocatalysts in an acidic environment:
      density functional theory study.
AB  - Density functional theory is employed to determine the reaction thermodynamics of
      a group of chemical and electrochemical reactions chosen to investigate the
      dissolution of metal atoms from oxygen reduction reaction catalysts in an acid
      medium. Once a set of thermodynamically allowed reactions is established, those
      reactions are selected to investigate the relative stabilities of Pt atoms and of
      other transition metal atoms (Ir, Pd, Rh, Ni, and Co) toward the dissolution
      reactions. The dissolution reactions that are found thermodynamically favorable
      are electrochemical and involve adsorbed oxygenated compounds that are
      intermediate species of the oxygen reduction reaction. Iridium is found to be the
      most stable among the various pure metals in comparison to Pt. Most of the metals
      alloyed with Pt cause a decrease of the Pt stability against dissolution, except
      for Ni, which does not affect it. On the other hand, the influence of Pt on the
      stability of the second metal in the alloy follows the same trend as in pure
      metal catalysts, with Ir being the most stable. When both atoms in a PtM alloy
      are involved in dissolution reactions, alloyed Ir is also found more stable than
      Pt in a given dissolution reaction, and the same behavior is found in alloyed Co
      for most of the reactions studied.

PMID- 16898678
TI  - Properties and reactivity of xanthyl radical in the excited state.
AB  - The properties and reactivity of the 9-xanthyl radical (X(*)) in the doublet
      excited state (X(*)(D(1))) were investigated using nanosecond-picosecond two
      color two-laser flash photolysis. The absorption and fluorescence spectra of
      X(*)(D(1)) were observed for the first time. The reactivity of X(*)(D(1)) toward
      a series of halogen donors and electron acceptors in acetonitrile and 1,2
      dichloroethane (DCE) was investigated. It is confirmed that X(*)(D(1)) has a
      halogen abstraction ability from a series of halogen donors. On the basis of the
      solvent effect on the quenching rate constants of X(*)(D(1)), an electron
      transfer from X(*)(D(1)) to CCl(4) was indicated.

PMID- 16898679
TI  - Analysis of wave packet motion in frequency and time domain: oxazine 1.
AB  - Wave packet motion in the laser dye oxazine 1 in methanol is investigated by
      spectrally resolved transient absorption spectroscopy. The spectral range of 600
      690 nm was accessible by amplified broadband probe pulses covering the overlap
      region of ground-state bleach and stimulated emission signal. The influence of
      vibrational wave packets on the optical signal is analyzed in the frequency
      domain and the time domain. For the analysis in the frequency domain an algorithm
      is presented that accounts for interference effects of neighbored vibrational
      modes. By this method amplitude, phase and decay time of vibrational modes are
      retrieved as a function of probe wavelength and distortions due to neighbored
      modes are reduced. The analysis of the data in the time domain yields
      complementary information on the intensity, central wavelength, and spectral
      width of the optical bleach spectrum due to wave packet motion.

PMID- 16898681
TI  - Laser-induced fluorescence spectra, structure, and the ring-twisting and ring
      bending vibrations of 1,4-benzodioxan in its S0 and S1(pi,pi*) states.
AB  - The laser-induced fluorescence (LIF) spectra, both the fluorescence excitation
      spectra (FES) and single vibrational level fluorescence spectra (SVLF) from
      several different vibronic states, along with the ultraviolet (UV) absorption
      spectra of 1,4-benzodioxan have been recorded and analyzed. A detailed energy map
      has been constructed for four low-frequency vibrations and their combinations for
      both the S(0) and S(1)(pi,pi) electronic states. These are nu(48) (ring-bending),
      nu(25) (ring-twisting), nu(47) (ring-flapping), and nu(24) (skeletal-twisting).
      Both the experimental and ab initio calculations show the molecule to be twisted
      in both the S(0) and S(1)(pi,pi) states with high barriers to planarity. The
      experimentally determined ring-twisting quantum states, which are confined to the
      lower regions of the potential energy surface, were used to calculate one
      dimensional potential functions in terms of the twisting coordinates, and the
      extrapolated barriers were estimated to be 5700 and 4200 cm(-1) for the S(0) and
      S(1) states, respectively. Two-dimensional calculations, which included the
      interactions with the bending modes, gave values of 3906 and 1744 cm(-1),
      respectively. The S(0) value compares favorably with the ab initio value of 4095
      cm(-1).

PMID- 16898680
TI  - An experimental and theoretical study of spin-spin coupling in chlorosilanes.
AB  - An experimental and theoretical study of the absolute value of the one-bond spin
      spin coupling constant |(1)J(Si,H)| in SiH(n)Cl(4-n) (n = 0-4) dissolved in THF
      d(8) is presented. We found |(1)J(Si,H)| to increase with an increasing number of
      chlorine substituents, and the quantitative changes were found to differ from the
      values previously reported for the same compounds dissolved in cyclohexane-d(12).
      We also report on the variations in |(1)J(Si,H)| as a function of temperature,
      which we found to be linearly temperature dependent for the chlorine-substituted
      silanes and temperature independent for SiH(4). Furthermore, the temperature
      dependence of |(1)J(Si,H)| varied between the different chlorosilanes. Solvent
      solute interactions were studied by quantum chemical DFT calculations. The
      variations in chloro-silane bond lengths upon adduct formation and the different
      adduct interaction energies may explain the temperature dependences of the
      coupling constants.

PMID- 16898682
TI  - Effect of pressure on the vibrational structure of insensitive energetic material
      5-nitro-2,4-dihydro-1,2,4-triazole-3-one.
AB  - The Raman spectra of alpha form 5-nitro-2,4-dihydro-1,2,4-triazole-3-one (alpha
      NTO, space group P) were measured in a high-pressure vessel diamond anvil cell
      (DAC). The pressure was increased to 27.6 GPa. In general, Raman bands show a
      blue shift because of the nature of the molecule packing as a high-pressure
      effect, but some particular bands exhibited a red shift, disappearance, split, or
      slight shifting in our experiments. Those red-shifting bands concerning hydrogen
      bonds, i.e., carbonyl and amino groups, are likely to work as a stabilizer
      against stimuli to the molecule or crystal. This stabilizing nature might
      characterize the insensitivity of NTO. Molecular dynamic (MD) calculations were
      performed to reveal the high-pressure effect of the alpha-NTO crystal. The
      coordinates of individual atoms in the crystal structure were obtained using X
      ray diffraction analysis. The pressure dependence of the power spectra of the
      correlation functions of the C=O bond length in NTO was calculated. A unique high
      pressure effect of the alpha-NTO crystal was found on the power spectra. The peak
      frequency in the power spectrum of the C=O stretching vibration exhibited a red
      shift with an increase in pressure to 10.0 GPa, while the peak intensity
      considerably decreased under the same pressure process, because this bond length
      increased with an increase in pressure to 10.0 GPa. At a pressure of >20.0 GPa, a
      blue shift appeared. These results of the MD calculations are in good agreement
      with our experimental data.

PMID- 16898683
TI  - Narrow-line and broadband spectra of iridium(III) complexes in a Shpol'skii
      matrix and an amorphous host.
AB  - Narrow-line emission and excitation spectra of the lowest triplet state have been
      studied in a Shpol'skii host (n-octane) for three cyclometalated IrL(2)acac
      complexes of current practical interest. The ligands L and acac are the C
      deprotonated anions of 2-phenylpyridine, 2-benzothienylpyridine, 1
      phenylisoquinoline, and acetylacetone. The occurrence of narrow lines is
      surprising for such nonplanar structures. Individual triplet sublevels are
      identified, and a striking intensity effect is observed in a magnetic field.
      Broadband spectra and lifetime data of the complexes in PMMA yield additional
      properties of the individual sublevels-radiative and nonradiative decay rates and
      emission spectra. The data are consistent with the assumption that these
      individual rates and spectra are approximately independent of temperature. For
      each complex, the decay rates vary by a factor of > or =20 among the three
      sublevels, and that of the lowest sublevel is the smallest, but rates of
      radiative and nonradiative decay generally vary in parallel for all three
      sublevels. The individual sublevels have significantly different spectra. These
      regularities appear to be universal characteristics of Ir(III) and Pt(II)
      complexes. They cannot be explained solely on the basis of the symmetries of the
      electronic states because the symmetry of the present complexes is too low.

PMID- 16898684
TI  - OH-stretching red shifts in bulky hydrogen-bonded alcohols: jet spectroscopy and
      modeling.
AB  - The available database for OH-stretching bands of jet-cooled aliphatic alcohol
      dimers is extended to systems including 1-adamantanol and 2-adamantanol, using a
      heated pulsed nozzle coupled to an FTIR spectrometer. This database is used to
      simplify and parametrize the standard Wang et al. AMBER/parm99.dat force field
      for the prediction of hydrogen-bond-induced red shifts, as it avoids
      complications due to mode coupling and cooperativity. Apart from subtle chiral
      recognition effects, the performance of the simple model in describing steric,
      electronic, and conformational influences on the red shifts is remarkable, as
      exemplified by predictions for mixed-alcohol dimers. The resulting semiempirical
      approach can complement quantum chemical calculations, in particular for larger
      systems, although the good performance is rather specific to red shift
      predictions.

PMID- 16898685
TI  - A new approach to explain concentration-dependent changes of isotropic Raman line
      width in the associated binary mixtures.
AB  - We report on a new empirical relationship to explain the concentration-dependent
      isotropic Raman line width changes of a vibrational mode in uniform binary
      mixtures. The factors contributing to the intrinsic line width and several other
      broadening mechanisms are, in general, concentration-dependent. Concentration
      fluctuation in a microscopic volume and microviscosity are the two factors that
      are known to cause a concentration-dependent line width variation. These two
      factors combined in a specific manner successfully explain the variation of the
      line width with concentration strongly associated with binary systems. A readily
      usable empirical relationship for line width is suggested. It has been
      demonstrated that it can successfully explain the line width variation with
      concentration in a given class of hydrogen-bonded systems taking some
      representative binary mixtures.

PMID- 16898686
TI  - Atmospheric chemistry of perfluorinated aldehyde hydrates (n-C(x)F(2x+1)CH(OH)2,
      x = 1, 3, 4): hydration, dehydration, and kinetics and mechanism of Cl atom and
      OH radical initiated oxidation.
AB  - Smog chamber/Fourier transform infrared (FTIR) techniques were used to measure
      k(Cl+C(x)F(2x+1)CH(OH)(2)) (x = 1, 3, 4) = (5.84 +/- 0.92) x 10(-13) and
      k(OH+C(x)F(2x+1)CH(OH)(2)) = (1.22 +/- 0.26) x 10(-13) cm(3) molecule(-1) s(-1)
      in 700 Torr of N(2) or air at 296 +/- 2 K. The Cl initiated oxidation of
      CF(3)CH(OH)(2) in 700 Torr of air gave CF(3)COOH in a molar yield of 101 +/- 6%.
      IR spectra of C(x)F(2x+1)CH(OH)(2) (x = 1, 3, 4) were recorded and are presented.
      An upper limit of k(CF(3)CHO+H(2)O) < 2 x 10(-23) cm(3) molecule(-1) s(-1) was
      established for the gas-phase hydration of CF(3)CHO. Bubbling CF(3)CHO/air
      mixtures through liquid water led to >80% conversion of CF(3)CHO into the hydrate
      within the approximately 2 s taken for passage through the bubbler. These results
      suggest that OH radical initiated oxidation of C(x)F(2x+1)CH(OH)(2) hydrates
      could be a significant source of perfluorinated carboxylic acids in the
      environment.

PMID- 16898687
TI  - Kinetic study of IO radical with RO2 (R = CH(3), C2H5, and CF3) using cavity ring
      down spectroscopy.
AB  - The reactions of iodine monoxide radical, IO, with alkyl peroxide radicals, RO(2)
      (R = CH(3), C(2)H(5), and CF(3)), have been studied using cavity ring-down
      spectroscopy. The rate constant of the reaction of IO with CH(3)O(2) was
      determined to be (7.0 +/- 3.0) x 10(-11) cm(3) molecule(-1) s(-1) at 298 K and
      100 Torr of N(2) diluent. The quoted uncertainty is two standard deviations. No
      significant pressure dependence of the rate constant was observed at 30-130 Torr
      total pressure of N(2) diluent. The temperature dependence of the rate constants
      was also studied at 213-298 K. The upper limit of the branching ratio of OIO
      radical formation from IO + CH(3)O(2) was estimated to be <0.1. The reaction rate
      constants of IO + C(2)H(5)O(2) and IO + CF(3)O(2) were determined to be (14 +/-
      6) x 10(-11) and (6.3 +/- 2.7) x 10(-11) cm(3) molecule(-1) s(-1) at 298 K, 100
      Torr of N(2) diluent, respectively. The upper limit of the reaction rate constant
      of IO with CH(3)I was <4 x 10(-14) cm(3) molecule(-1) s(-1).

PMID- 16898688
TI  - Experimental investigation of toluene + H --> benzyl + H2 at high temperatures.
AB  - The reaction of toluene with hydrogen atoms yielding benzyl and molecular
      hydrogen, C(6)H(5)CH(3) + H --> C(6)H(5)CH(2) + H(2), was investigated using UV
      laser absorption of benzyl radicals at 266 nm in shock tube experiments. Test gas
      mixtures of toluene and ethyl iodide, an H-atom source, diluted in argon were
      heated in reflected shock waves to temperatures ranging from 1256 to 1667 K at
      total pressures around 1.7 bar. Measurement of laser absorption at 266 nm due to
      benzyl radicals allowed determination of the rate coefficient of the title
      reaction, reaction 1. A two-parameter best-fit Arrhenius expression for the rate
      determinations over the temperature range of these experiments is given by
      k(1)(T) = 1.33 x 10(15) exp(-14880 [cal/mol]/RT) [cm(3) mol(-1) s(-1)]. With the
      use of both the high-temperature shock tube measurements reported here and the
      rate coefficient determination of Ellis et al. (Ellis, C.; Scott, M. S.; Walker,
      R. W. Combust. Flame 2003, 132, 291) at 773 K the best-fit rate coefficient for
      reaction 1 can be described using a three-parameter Arrhenius expression by
      k(1)(T) = 6.47T (3.98) exp(-3384 [cal/mol]/RT) [cm(3) mol(-1) s(-1)].

PMID- 16898689
TI  - Formation and decay of the triplet excited state of pyridine.
AB  - A pulse radiolysis study of the formation and decay of the triplet excited state
      of liquid pyridine has been performed using quenching techniques. The pyridine
      triplet excited state is observed with an absorption band at lambda = 310 nm and
      has a first-order decay with a lifetime of 72 ns. Stern-Volmer plots of the
      quenching of the pyridine triplet excited state with anthracene, naphthalene, and
      biphenyl give its yield to be 1.3 molecules/100 eV. This value is very similar to
      the previously determined yield of 1.25 molecules/100 eV for dipyridyl, the
      predominant condensed-phase product in the gamma-radiolysis of liquid pyridine.
      The rate coefficient for pyridine triplet excited-state scavenging by oxygen is
      estimated to be 6.6 x 10(9) M(-1) s(-1). Oxygen may also scavenge the electron
      precursor to the pyridine triplet excited state, whereas nitrous oxide is
      observed to have little effect. A pyridyl radical-pyridine (dimer) complex
      produced in the pulse radiolysis of neat liquid pyridine is detected at lambda =
      390 nm and is consistent with iodine scavenging effects. Formation of the
      pyridiniumyl radical cation-pyridine charge-transfer complex is proposed to be
      insignificant in liquid pyridine.

PMID- 16898691
TI  - Lone-pair orbital interactions in polythiaadamantanes.
AB  - The electronic structures of a series of polythiaadamantanes from thiaadamantane
      through 2,4,6,8,9,10-hexathiaadamantane (HTA) have been analyzed using density
      functional theory calculations in conjunction with Huckel and natural bond
      orbital analysis. The effects of multiple sulfur p-type lone-pair orbital
      interactions on ionization potentials, hole mobilities, and electronic coupling
      have been determined. An overall increase in the average energy of the lone-pair
      orbitals as the number of sulfur atoms increases is predicted, with the exact
      positioning of the HOMO depending on specific lone-pair interactions. Separation
      of through-bond (TB) and through-space (TS) interactions between intramolecular
      sulfur atoms has been performed using localized molecular orbitals and model
      systems based on interacting hydrogen sulfide molecules. TB interations were
      found to reduce orbital splitting, while TS interactions were found to increase
      orbital splitting. TS interactions were more or less constant from one
      polythiaadamantane to the next, and the contributions of TB effects to individual
      orbital energies vary depending on the relative orientation of sulfur atoms as
      determined by the sigma molecular framework. Electronic coupling between
      intermolecular sulfur lone-pair orbitals was determined by investigating unique
      dimer pairs observed in the crystal structure of HTA. Electronic coupling is not
      as strong as expected given the short intermolecular S-S distances observed in
      the crystal structure. In general, B3LYP/6-31G(d) and B3LYP/6-311+G(d,p) give
      very similar orbital energies and splittings.

PMID- 16898690
TI  - An apparent angle dependence for the nonradiative deactivation of excited triplet
      states of sterically constrained, binuclear ruthenium(II) bis(2,2':6',2' '
      terpyridine) complexes.
AB  - The photophysical properties are reported for a series of binuclear ruthenium(II)
      bis(2,2':6',2"-terpyridine) complexes built around a geometrically constrained,
      biphenyl-based bridge. The luminescence quantum yield and lifetime increase
      progressively with decreasing temperature, but the derived rate constant for
      nonradiative decay of the lowest-energy triplet state depends on the length of a
      tethering strap attached at the 2,2'-positions of the biphenyl unit. Since the
      length of the strap determines the dihedral angle for the central C-C bond, the
      rate of nonradiative decay shows a pronounced dependence on angle. The minimum
      rate of nonradiative decay occurs when the dihedral angle is 90 degrees, but
      there is a maximum in the rate when the dihedral angle is about 45 degrees. This
      effect does not appear to be related to the extent of electron delocalization at
      the triplet level but can be explained in terms of variable coupling with a low
      frequency vibrational mode associated with the strapped biphenyl unit.

PMID- 16898692
TI  - Theoretical study on the complete series of chloroanilines.
AB  - The environmental effects of chloroanilines depend on their physical and chemical
      properties, and it is therefore important to know their structure-property
      relationships that allow a complete understanding of their environmental
      consequences. The chemical reactivity profiles of all 19 chloroanilines have been
      investigated using the density functional theory for the first time. Global
      reactivity descriptors, such as hardness, chemical potential, electrophilicity
      index, and polarizability, and local reactivity descriptors, namely, local
      philicities, have been calculated in order to gain insights into the reactive
      nature and the reactive sites of the selected systems. Using AIM theory, the
      presence of hydrogen bond critical points (HBCPs) and the values of electron
      density and Laplacian of electron density at the HBCPs have been analyzed to
      appreciate the presence of intramolecular hydrogen bonding in the selected
      systems. Structure-toxicity analysis of the selected set of chloroanilines
      demonstrates the importance of the electrophilicity index in the prediction of
      reactivity/toxicity.

PMID- 16898693
TI  - Modeling competitive reaction mechanisms of peroxynitrite oxidation of guanine.
AB  - 5-Guanidino-4-nitroimidazole is a stable product from the peroxynitrite induced
      one-electron oxidation of guanine. Reaction mechanisms to form the 5-guanidino-4
      nitroimidazole as well as 8-nitroguanine, through the combination of the guanine
      radical cation and nitrogen dioxide radical and through the combination of the
      deprotonated neutral guanine radical and nitrogen dioxide radical, have been
      investigated by the use of the B3LYP method of density functional theory. Our
      calculations suggest that the guanine radical cation mechanism is preferred over
      the neutral guanine radical mechanism and that a water molecule is involved in
      the reaction as a catalyst or as a reactant.

PMID- 16898694
TI  - On the nature of unrestricted orbitals in variational active space wave
      functions.
AB  - Active space coupled cluster methods exhibit unusual, nonsmooth spin symmetry
      breaking behavior where the unrestricted minimum lies higher in energy at short
      bond distances and crosses below the restricted solution at longer distances. The
      restricted solution is also observed to be a stable minimum slightly beyond the
      symmetry-breaking point. This behavior arises due to differences in the optimal
      active spaces defining the restricted and unrestricted wave functions and results
      in unrestricted wave functions that are not strictly size consistent. We suggest
      a new, size-consistent model that allows the orbitals to break spin symmetry only
      within the active space.

PMID- 16898695
TI  - Theoretical study of unsymmetrical bisfullerene and its derivatives: C131,
      C129BN, and C130Si.
AB  - Unsymmetrical bisfullerene C(131) and its derivatives such as C(129)BN and
      C(130)Si are systematically investigated by semiempirical and density functional
      theory approaches. In comparison with the experimental data, calculated IR and
      NMR results reveal that both C(131)(H) and C(131)(P) isomers are possible
      compounds to coexist in the synthesized product. The C/Si and CC/BN substitution
      can change the electronic properties and reactivities compared with the pristine
      C(131)(H) and C(131)(P), respectively.

PMID- 16898696
TI  - Fermi resonances of borohydrides in a crystalline environment of alkali metals.
AB  - Vibrational spectra of BH(4)(-) and its isotopic analogues in a crystalline
      environment of alkali metals cations (K(+), Rb(+), Cs(+)) have been investigated
      beyond the harmonic approximation using a variational approach supported by
      computations of B3LYP type anharmonic force fields. From the comparison of the
      observed and simulated IR spectra, the influence of the anharmonic couplings on
      the band position and on the relative intensity of the allowed vibrational
      transitions is discussed. Here, the effect of the crystalline environment induces
      a blue shift of about 50 and 100 cm(-1) respectively for the bending and
      stretching modes of BH(4)(-). Furthermore, anharmonic effects, which are
      exclusively well reproduced by a variational approach, are needed to yield
      reliable positions and relative amplitudes of IR allowed combination and overtone
      transitions. This leads to theoretical results fitting their experimental
      counterpart between 6 and 30 cm(-1) in the investigated series.

PMID- 16898697
TI  - Quantum mechanical analysis of 1,2-ethanediol conformational energetics and
      hydrogen bonding.
AB  - A proper understanding of the conformational energetics of 1,2-ethanediol
      (ethylene glycol) is important to the construction of molecular mechanics force
      fields for the treatment of carbohydrates since these biologically important
      molecules have a prevalence of vicinal hydroxyl groups. In the present study,
      quantum mechanical analysis of the 10 unique minimum-energy conformations of
      ethylene glycol is performed by using 10 model chemistries ranging from HF/6
      311++G(d,p) up to a hybrid method that approximates CCSD(T)/cc-pVQZ. In addition,
      natural bond orbital (NBO) analysis of these conformations with deletion of
      pairings of CO bond/antibonding and lone pair/antibonding orbitals is used to
      investigate contributions from the "gauche" effect to ethylene glycol
      conformational energetics. MP2 with the "correlation consistent" basis sets and
      DFT/6-311++G(d,p) do the best job of matching the approximate CCSD(T)/cc-pVQZ
      energies while MP2/6-31G(d) and Hartree-Fock both fare poorly. NBO analysis shows
      the conformational energies to be independent of the deletion of matrix elements
      associated with (i) CO bonding and antibonding orbital interactions and (ii) lone
      pair and antibonding orbital interactions, whereas the energetic ordering
      correlates with geometric parameters consistent with internal hydrogen bonds.
      Thus, the present results suggest that standard molecular mechanics potential
      energy functional forms, which lack explicit terms to account for
      stereoelectronic effects, are appropriate for carbohydrates.

PMID- 16898698
TI  - Aryl sulfoxide radical cations. Generation, spectral properties, and theoretical
      calculations.
AB  - Aromatic sulfoxide radical cations have been generated by pulse radiolysis and
      laser flash photolysis techniques. In water (pulse radiolysis) the radical
      cations showed an intense absorption band in the UV region (ca. 300 nm) and a
      broad less intense band in the visible region (from 500 to 1000 nm) whose
      position depends on the nature of the ring substituent. At very low pulse energy,
      the radical cations decayed by first-order kinetics, the decay rate increasing as
      the pH increases. It is suggested that the decay involves a nucleophilic attack
      of H(2)O or OH(-) (in basic solutions) to the positively charged sulfur atom to
      give the radical ArSO(OH)CH(3)(*). By sensitized [N-methylquinolinium
      tetrafluoborate (NMQ(+))] laser flash photolysis (LFP) the aromatic sulfoxide
      radical cations were generated in acetonitrile. In these experiments, however,
      only the band of the radical cation in the visible region could be observed, the
      UV band being covered by the UV absorption of NMQ(+). The lambda(max) values of
      the bands in the visible region resulted almost identical to those observed in
      water for the same radical cations. In the LFP experiments the sulfoxide radical
      cations decayed by second-order kinetics at a diffusion-controlled rate, and the
      decay is attributed to the back electron transfer between the radical cation and
      NMQ(*). DFT calculations were also carried out for a number of 4-X ring
      substituted (X = H, Me, Br, OMe, CN) aromatic sulfoxide radical cations (and
      their neutral parents). In all radical cations, the conformation with the S-O
      bond almost coplanar with the aromatic ring is the only one corresponding to the
      energy minimum. The maximum of energy corresponds to the conformation where the S
      O bond is perpendicular to the aromatic ring. The rotational energy barriers are
      not very high, ranging from 3.9 to 6.9 kcal/mol. In all radical cations, the
      major fraction of charge and spin density is localized on the SOMe group.
      However, a substantial delocalization of charge and spin on the ring (almost 50%
      for the 4-methoxy derivative and around 30% for the other radical cations) is
      also observed. This suggests some conjugative interaction between the MeSO group
      and the aromatic system that may become very significant when a strong electron
      donating substituent like the MeO group is present. The ionization energies (IE)
      of the 4-X ring substituted neutral aromatic sulfoxides were also calculated,
      which were found to satisfactorily correlate with the experimental E(p)
      potentials measured by cyclic voltammetry.

PMID- 16898699
TI  - Effect of ring substitution on the S-H bond dissociation enthalpies of
      thiophenols. An experimental and computational study.
AB  - There are conflicting reports on the origin of the effect of Y substituents on
      the S-H bond dissociation enthalpies (BDEs) in 4-Y-substituted thiophenols, 4
      YC(6)H(4)S-H. The differences in S-H BDEs, [4-YC(6)H(4)S-H] - [C(6)H(5)S-H], are
      known as the total (de)stabilization enthalpies, TSEs, where TSE = RSE - MSE,
      i.e., the radical (de)stabilization enthalpy minus the molecule (de)stabilization
      enthalpy. The effects of 4-Y substituents on the S-H BDEs in thiophenols and on
      the S-C BDEs in phenyl thioethers are expected to be almost identical. Some S-C
      TSEs were therefore derived from the rates of homolyses of a few 4-Y-substituted
      phenyl benzyl sulfides, 4-YC(6)H(4)S-CH(2)C(6)H(5), in the hydrogen donor solvent
      9,10-dihydroanthracene. These TSEs were found to be -3.6 +/- 0.5 (Y = NH(2)), 
      1.8 +/- 0.5 (CH(3)O), 0 (H), and 0.7 +/- 0.5 (CN) kcal mol(-1). The MSEs of 4
      YC(6)H(4)SCH(2)C(6)H(5) have also been derived from the results of combustion
      calorimetry, Calvet-drop calorimetry, and computational chemistry (B3LYP/6
      311+G(d,p)). The MSEs of these thioethers were -0.6 +/- 1.1 (NH(2)), -0.4 +/- 1.1
      (CH(3)O), 0 (H), -0.3 +/- 1.3 (CN), and -0.8 +/- 1.5 (COCH(3)) kcal mol(-1).
      Although all the enthalpic data are rather small, it is concluded that the TSEs
      in 4-YC(6)H(4)SH are largely governed by the RSEs, a somewhat surprising
      conclusion in view of the experimental fact that the unpaired electron in
      C(6)H(5)S(*) is mainly localized on the S. The TSEs, RSEs, and MSEs have also
      been computed for a much larger series of 4-YC(6)H(4)SH and 4-YC(6)H(4)SCH(3)
      compounds by using a B3P86 methology and have further confirmed that the S-H/S
      CH(3) TSEs are dominated by the RSEs. Good linear correlations were obtained for
      TSE = rho(+)sigma(p)(+)(Y), with rho(+) (kcal mol(-1)) = 3.5 (S-H) and 3.9 (S
      CH(3)). It is also concluded that the SH substituent is a rather strong electron
      donor with a sigma(p)(+)(SH) of -0.60, and that the literature value of -0.03 is
      in error. In addition, the SH rotational barriers in 4-YC(6)H(4)SH have been
      computed and it has been found that for strong electron donating (ED) Ys, such as
      NH(2), the lowest energy conformer has the S-H bond oriented perpendicular to the
      aromatic ring plane. In this orientation the SH becomes an electron withdrawing
      (EW) group. Thus, although the OH group in phenols is always in-plane and ED
      irrespective of the nature of the 4-Y substituent, in thiophenols the SH switches
      from being an ED group with EW and weak ED 4-Ys, to being an EW group for strong
      ED 4-Ys.

PMID- 16898700
TI  - An ab initio study of 15N-11B spin-spin coupling constants for borazine and
      selected derivatives.
AB  - Ab initio equation-of-motion coupled-cluster singles and doubles (EOM-CCSD)
      calculations have been performed to investigate substituent effects on coupling
      constants for borazine and selected substituted borazines. For molecules in which
      F atoms are not bonded to adjacent atoms in the ring, F substitution increases
      the one-bond (11)B-(15)N coupling constants involving the atom at which
      substitution occurs but leaves the remaining one-bond B-N coupling constants
      essentially unchanged. For these molecules, the magnitudes of one-bond B-N
      coupling constants are only slightly dependent on the number of F atoms present.
      Fluorine substitution at adjacent B and N atoms in the borazine ring further
      increases the one-bond B-N coupling constant involving the substituted atoms and
      has the same effect on the other one-bond coupling constants as observed for
      corresponding molecules in which substitution occurs at alternate sites. In
      contrast to the effect of F substitution, substitution of Li at either N or B
      decreases one-bond B-N coupling constants relative to borazine. The effects of F
      and Li substitution on one-bond B-N coupling constants for borazine are similar
      to F and Li substitution effects on (13)C-(13)C coupling constants for benzene.

PMID- 16898702
TI  - Three-center-two-electron and four-center-four-electron bonds. A study by
      electron charge density over the structure of methonium cations.
AB  - We study the electronic density charge topology of CH(5)(+) species 1 (C(s)()), 2
      (C(s)()), and 3 (C(2)(v)) at ab initio level using the theory of atoms in
      molecules developed by Bader. Despite the reports of previous studies concerning
      carbocationic species, the methane molecule is protonated at the carbon atom,
      which clearly shows its pentacoordination. In addition to the fact that hydrogen
      atoms in the methonium molecule behave in a very fluxional fashion and that the
      energy difference among the species 1, 2, and 3 are very low, is important to
      point out that two different topological situations can be defined on the basis
      of our study of the topology of the electronic charge density. Then, the species
      1 and 2 present a three-center-two-electron (3c-2e) bond of singular
      characteristics as compared with other carbocationic species, but in the species
      3, the absence of a 3c-2e bond is noteworthy. This structure can be characterized
      through the three bond critical points found, corresponding to saddle points on
      the path bonds between the C-H(2,3,5) that lie in the same plane. These nuclei
      define a four-center interaction where the electronic delocalization produced
      among the sigma(C-H) bonds provide a stabilization of the three C-H bonds
      involved in this interaction (the remaining two C-H bonds are similar to those
      belonging to the nonprotonated species). Our results show that bonding situations
      with a higher number of atom arrays are possible in protonated hydrocarbons.

PMID- 16898701
TI  - Linear and nonlinear optical response of aromatic amino acids: a time-dependent
      density functional investigation.
AB  - The linear and nonlinear optical responses of the three aromatic amino acids
      tryptophan, tyrosine, and phenylalanine have been investigated by time-dependent
      density functional theory. The effect of the peptidic chain on the
      polarizabilities and the first hyperpolarizabilities is addressed by substituting
      different groups to the chromophores indole, phenol, and benzene. The optimized
      structures are in very good agreement with the experimental results. Furthermore,
      the calculated polarizabilities are found to match well with the empirical
      results, showing the evolution obtained as the chain is lengthened. A systematic
      and constant increase of the polarizability is found, for the three chromophores,
      for the various chain lengths. The first hyperpolarizability is also noticeably
      modified by the chains, but the evolution of this quantity is found to be more
      dependent on the system considered. Finally, it is suggested that each of the
      three aromatic amino acids has a significant contribution to the nonlinear
      response of proteins.

PMID- 16898703
TI  - High-resolution X-ray photoelectron spectroscopy of chlorine-terminated
      GaAs(111)A surfaces.
AB  - Oxide-terminated and Cl-terminated GaAs(111)A surfaces have been characterized in
      the As and Ga 3d regions by high-resolution, soft X-ray photoelectron
      spectroscopy. The Cl-terminated surface, formed by treatment with 6 M HCl(aq),
      showed no detectable As oxides or As(0) in the As 3d region. The Ga 3d spectrum
      of the Cl-terminated surface showed a broad, intense signal at 19.4 eV and a
      smaller signal at 21.7 eV. The Ga 3d peaks were fitted using three species, one
      representing bulk GaAs and the others representing two chemical species on the
      surface. The large peak was well-fitted by the bulk GaAs emission and by a second
      doublet, assigned to surface Ga atoms bonded to Cl, that was shifted by 0.34 eV
      from the bulk GaAs 3d emission. The smaller peak, shifted by 2.3 eV in binding
      energy relative to the bulk GaAs Ga 3d signal, is assigned to Ga(OH)3. The data
      confirm that wet chemical etching allows for the formation of well-defined, Cl
      terminated GaAs(111)A surfaces free of detectable elemental As, that can provide
      a starting point for further functionalization of GaAs.

PMID- 16898704
TI  - Edge-on bonding of benzene molecules in the second adsorbed layer on Cu(110).
AB  - The bilayer of benzene on Cu(110) was studied with temperature-programmed
      desorption (TPD), time-of-flight electron stimulated desorption ion angular
      distribution (TOF-ESDIAD), and scanning tunneling microscopy (STM). TPD spectra
      show that three well-defined adsorption states exist. The alpha layer corresponds
      to the first layer containing flat-lying benzene molecules. As coverage
      increases, the beta layer forms on top of the alpha layer, and eventually, a
      multilayer, gamma, forms. TPD measurements show that the number of benzene
      molecules in the beta layer is equal to the number of benzene molecules in the
      alpha layer. ESDIAD measurements establish that the orientation of the benzene
      molecules in the beta layer is edge-on, with two C-H bonds directed toward the
      surface. STM images of the beta layer reveal closely spaced edge-on benzene
      molecules arranged in repeating hexagons, as well as loosely spaced benzene
      molecules with greater apparent height, which are also edge-on species.
      Correlation between the different measurements suggests a structural model for
      the benzene bilayer.

PMID- 16898705
TI  - Role of solvation in the energy stabilization inside the hydrophobic core of the
      protein rubredoxin.
AB  - There are many forces that contribute to the stability of a protein; among these
      are dispersion interactions, hydrogen bonding, and solvation effects. In a recent
      work, Vondrasek et al. estimated the in vacuo stabilization energy of the
      hydrophobic core of the protein rubredoxin using high level ab initio methods
      (Vondrasek, J.; et al. J. Am. Chem. Soc. 2005, 127, 2615). In this work, we
      evaluate the effects of solvation on the stability of the hydrophobic core of
      this protein. Solvation calculations are made using the polarizable continuum
      method at the MP2/aug-cc-pVDZ level of theory. It is found that, in a protein
      like environment (mimicked by a continuum solvent with a dielectric constant of
      approximately 4), the stability of rubredoxin's hydrophobic core is decreased by
      40-50%. We also observed that the stabilization energy of the hydrophobic core is
      only slightly lower in a protein-like medium than in an aqueous one (DeltaGether
      DeltaGwater approximately 1.0-3.5 kcal/mol).

PMID- 16898706
TI  - Role of the middle residue in the triple tryptophan electron transfer chain of
      DNA photolyase: ultrafast spectroscopy of a Trp-->Phe mutant.
AB  - Photoreduction of the semi-reduced flavin adenine dinucleotide cofactor FADH* in
      DNA photolyase from Escherichia coli into FADH- involves three tryptophan (W)
      residues that form a closely spaced electron-transfer chain FADH*-W382-W359-W306.
      To investigate this process, we have constructed a mutant photolyase in which
      W359 is replaced by phenylalanine (F). Monitoring its photoproducts by
      femtosecond spectroscopy, the excited-state FADH* was found to decay in
      approximately 30 ps, similar as in wild type (WT) photolyase. In contrast to WT,
      however, in W359F mutant photolyase the ground-state FADH* fully recovered
      virtually concomitantly with the decay of its excited state and, despite the
      presence of the primary electron donor W382, no measurable flavin reduction was
      observed at any time. Thus, W359F photolyase appears to behave like many other
      flavoproteins, where flavin excited states are quenched by very short-lived
      oxidation of aromatic residues. Our analysis indicates that both charge
      recombination of the primary charge separation state FADH-W382*+ and (in WT)
      electron transfer from W359 to W382*+ occur with time constants <4 ps,
      considerably faster than the initial W382-->FADH* electron-transfer step. Our
      results provide a first experimental indication that electron transfer between
      aromatic residues can take place on the time scale of approximately 10(-12) s.

PMID- 16898707
TI  - Angular and local spectroscopic analysis to probe the vertical alignment of N
      doped well-separated carbon nanotubes.
AB  - Vertically aligned well-separated N-doped multiwalled carbon nanotubes (CNTs)
      were grown on a silicon substrate by plasma enhanced chemical vapor deposition
      (PECVD). Angular near-edge X-ray absorption fine structure (NEXAFS) was used to
      investigate the vertical alignment of as-grown CNTs. In addition, both individual
      tubes and tube bundles were characterized by high-resolution electron energy loss
      spectroscopy (HREELS). Simultaneous analysis of both spectroscopic techniques
      provides information on chemical environment, orbital orientation between carbon
      and heteroatoms, and local curvature effects. We demonstrate the utility of
      NEXAFS as an in situ probe of CNTs.

PMID- 16898708
TI  - Rich coordination chemistry of Au adatoms in gold sulfide monolayer on Au(111).
AB  - The rich chemistry of Au nanoparticles and ions has attracted tremendous
      interest, in part because the surfaces of bulk Au have traditionally been
      considered to be chemically inert. On the other hand, large-scale mass transport
      and the formation of vacancy islands have been observed on the Au(111) surface
      following the deposition of adsorbates, such as sulfur and thiols, that can
      interact strongly with the Au surface. In this work, we revisit the structure and
      chemistry of an ordered incommensurate AuS adlayer that forms on Au(111)
      following the deposition of sulfur and annealing to 450 K. A structural model of
      this AuS surface phase has not yet been determined experimentally due to the
      complexity of the system. Here, we use state-of-the-art density functional theory
      to develop an atomic-scale model that is consistent with the previously reported
      Au-S stoichiometry. In particular, we introduce theoretical techniques to take
      into account the charge transfer in an incommensurate system. Our model
      reproduces convincingly STM images and is remarkably robust. Bonding analysis
      based on Wannier functions shows that the model exhibits rich coordination
      chemistry corresponding to different Au oxidation states. The extraordinary
      stability and rich chemistry of this structure have implications for related S-Au
      interfaces and previously reported surface features of this system.

PMID- 16898709
TI  - Maneuvering the surface plasmon resonance of silver nanostructures through shape
      controlled synthesis.
AB  - Silver nanostructures are containers for surface plasmons - the collective
      oscillation of conduction electrons in phase with incident light. By controlling
      the shape of the container, one can control the ways in which electrons
      oscillate, and in turn how the nanostructure scatters light, absorbs light, and
      enhances local electric fields. With a series of discrete dipole approximation
      (DDA) calculations, each of a distinctive morphology, we illustrate how shape
      control can tune the optical properties of silver nanostructures. Calculated
      predictions are validated by experimental measurements performed on nanocubes
      with controllable corner truncation, right bipyramids, and pentagonal nanowires.
      Control of nanostructure shape allows optimization of plasmon resonance for
      molecular detection and spectroscopy.

PMID- 16898710
TI  - A new redox-resettable molecule-based half-adder with tetrathiafulvalene.
AB  - A new redox molecule-based half-adder with tetrathiafulvalene (TTF) was reported
      for the first time. This half-adder employs electrochemical and chemical
      oxidations (NOPF6) as input signals and absorbances at 350 and 435 nm as output
      signals. It is interesting to note that this new molecule-based half-adder shows
      reset capability by making use of the unique redox behaviors of TTF.

PMID- 16898711
TI  - Phase biaxiality in nematic liquid crystalline side-chain polymers of various
      chemical constitutions.
AB  - In a previous deuterium NMR study conducted on a liquid crystalline (LC) polymer
      with laterally attached book-shaped molecules as the mesogenic moiety, we have
      revealed a biaxial nematic phase below the conventional uniaxial nematic phase
      (Phys. Rev. Lett. 2004, 92, 125501). To elucidate details of its formation, we
      here report on deuterium NMR experiments that have been conducted on different
      types of LC side-chain polymers as well as on mixtures with low-molar-mass
      mesogens. Different parameters that affect the formation of a biaxial nematic
      phase, such as the geometry of the attachment, the spacer length between the
      polymer backbone and the mesogenic unit, as well as the polymer dynamics, were
      investigated. Surprisingly, also polymers with terminally attached mesogens (end
      on polymers) are capable of forming biaxial nematic phases if the flexible spacer
      is short and thus retains a coupling between the polymer backbone and the LC
      phase. Furthermore, the most important parameter for the formation of a biaxial
      nematic phase is the dynamics of the polymer backbone, as the addition of a small
      percentage of low molar mass LC to the biaxial nematic polymer from the original
      study served to shift both the glass transition and the appearance of detectable
      biaxiality in a very similar fashion. Plotting different parameters for the
      investigated systems as a function of T/Tg also reveals the crucial role of the
      dynamics of the polymer backbone and hence the glass transition.

PMID- 16898712
TI  - Hierarchical saw-like ZnO nanobelt/ZnS nanowire heterostructures induced by polar
      surfaces.
AB  - Saw-like nanostructures composed of single-crystalline ZnO nanobelts and single
      crystalline ZnS nanowires have been successfully synthesized by a vapor-solid
      process. Several techniques, including scanning electron microscope, transmission
      electron microscopy, and photoluminescence spectroscopy, were used to investigate
      the structures, morphology, and photoluminescence properties of the products. Due
      to the similar crystal habits of wurtzite ZnO and ZnS with chemically active Zn
      terminated (0001) and chemically inactive O-terminated (or S-terminated) (000)
      polar surfaces, hierarchical saw-like nanostructures were considered to be formed
      by the initiation of a chemically active Zn-terminated ZnO (0001) polar surface.
      Photoluminescence properties of the heterostructures, different from pure ZnO
      nanobelts or ZnS nanowires, were also studied at room temperature.

PMID- 16898713
TI  - Origin of enhanced crystal growth kinetics near Tg probed with indomethacin
      polymorphs.
AB  - Using three crystal polymorphs of indomethacin (IMC), we tested two
      interpretations of the enhanced crystal growth kinetics near the glass transition
      temperature Tg. This enhancement refers to the stronger temperature dependence of
      liquid viscosity eta than crystal growth rate (corrected for thermodynamic
      driving force). This enhancement is attributed in the first interpretation to an
      increase of the number of preferred interfacial growth sites with decreasing
      temperature and, in the second interpretation, to the breakdown of the Stokes
      Einstein relation in deeply supercooled liquids. We measured the growth rates of
      the IMC polymorphs (alpha, gamma, and delta) from Tg + 9 K (Tg = 314 K) to near
      the respective melting points. From Tg + 19 K to Tg + 69 K, the growth rates of
      the polymorphs changed by 10(4) fold but displayed the same temperature
      dependence (eta-0.78) after corrections for thermodynamic driving forces. These
      results argue for a liquid-state origin of the enhanced growth kinetics. Below
      ca. Tg + 19 K, delta IMC continued to grow in the same spherulite morphology but
      alpha and gamma IMC grew in different, fiberlike morphologies and, if measured
      consistently, at faster rates. We conclude that the liquid dynamics of IMC
      controls its crystal growth kinetics over a wide range of temperatures but
      changes of growth morphologies near Tg also lead to apparent acceleration of
      growth of certain polymorphs. This work also extended a previous study of D
      sorbitol to lower temperatures to enable a broader analysis of crystal growth
      kinetics of organic molecules near Tg.

PMID- 16898714
TI  - Turkevich method for gold nanoparticle synthesis revisited.
AB  - The growth of gold nanoparticles by reduction by citrate and ascorbic acid has
      been examined in detail to explore the parameter space of reaction conditions. It
      is found that gold particles can be produced in a wide range of sizes, from 9 to
      120 nm, with defined size distribution, following the earlier work of Turkevich
      and Frens. The reaction is initiated thermally or in comparison by UV
      irradiation, which results in similar final products. The kinetics of the
      extinction spectra show the multiple steps of primary and secondary clustering
      leading to polycrystallites.

PMID- 16898715
TI  - Debundling of single-walled nanotubes by dilution: observation of large
      populations of individual nanotubes in amide solvent dispersions.
AB  - Large-scale debundling of single-walled nanotubes has been demonstrated by
      dilution of nanotube dispersions in the solvent N-methyl-2-pyrrolidone (NMP). At
      high concentrations some very large (approximately 100 s of micrometers) nanotube
      aggregates exist that can be removed by mild centrifugation. By measurement of
      the absorbance before and after centrifugation as a function of concentration the
      relative aggregate and dispersed nanotube concentrations can be monitored. No
      aggregates are observed below CNT approximately 0.02 mg/mL, suggesting that this
      can be considered the nanotube dispersion limit in NMP. After centrifugation, the
      dispersions are stable against sedimentation and further aggregation for a period
      of weeks at least. Atomic force microscopy (AFM) studies on deposited films
      reveal that the bundle diameter distribution decreases dramatically as
      concentration is decreased. Detailed data analysis suggests the presence of an
      equilibrium bundle number density and that the dispersions self-arrange
      themselves to always remain close to the dilute/semidilute boundary. A population
      of individual nanotubes is always observed that increases with decreasing
      concentration until almost 70% of all dispersed objects are individual nanotubes
      at a concentration of 0.004 mg/mL. The number density of individual nanotubes
      peaks at a concentration of approximately 10(-2) mg/mL. Both the mass fraction
      and the partial concentration of individual nanotubes can also be measured and
      behave in similar fashion. Comparison of the number density and partial
      concentration also of individual nanotubes reveals that the individual nanotubes
      have average molar masses of approximately 700,000 g/mol. The presence of
      individual nanotubes in NMP dispersion was confirmed by photoluminescence
      spectroscopy. Concentration dependence of the photoluminescence intensity
      confirms that the AFM measurements reflect the diameter distributions in situ. In
      addition, Raman spectroscopy confirms the presence of large quantities of
      individual nanotubes in the deposited films. Finally, the nature of the solvent
      properties required for dispersion are discussed.

PMID- 16898716
TI  - Electrochemistry and electrogenerated chemiluminescence of all-trans conjugated
      polymer poly[distyrylbenzene-b-(ethylene oxide)]s.
AB  - The electrochemistry and electrogenerated chemiluminescence (ECL) of two linear,
      stereoregular, and structurally defined PPV derivatives, poly[distyrylbenzene-b
      (ethylene oxide)]s, with respective 12 and 16 of ethylene oxide repeat units in
      the backbone, abbreviated as DE-1 and DE-2, have been studied on glassy carbon
      and Pt electrodes in CH2Cl2 and CH3CN containing 0.10 M tetra-n-butylammonium
      perchlorate (TBAP). In CH2Cl2, a one-electron transfer, reversible oxidation at
      approximately 0.75 V vs Ag/Ag+ (10 mM AgNO3 in CH3CN) was observed for both
      polymers. Porous polymer films were electrochemically formed on the electrode
      with multiple cyclic potential scanning. Cast films of DE-1 and DE-2 on the
      electrode prepared from 1.0 mM of the corresponding CH2Cl2 solutions were used
      for studies in CH3CN containing 0.10 M TBAP due to their limited solubility in
      the solvent. A film-type of oxidation was found at approximately 0.80 V vs Ag/Ag+
      in CH3CN when a scan rate of less than 1 V/s was used. The soluble oxidation
      product can be captured and reduced and then reoxidized in solution-phase at the
      electrode at a relatively high scan rate of, e.g., 2 V/s. ECL responses with a
      maximum emission at approximately 1.10 V vs Ag/Ag+ were obtained with the cast
      films in CH3CN (0.10 M TBAP) in the presence of 43 mM tri-n-propylamine (TPrA)
      after both TPrA and film were oxidized. The ECL is believed to be resulted from
      the interaction between the oxidized polymer species and the strong reducing TPrA
      free radical (TPrA*) generated after the deprotonation of TPrA*+ cation species.

PMID- 16898717
TI  - High-density, aligned SiO2 nanowire arrays: microscopic imaging of the unique
      growth style and their ultraviolet light emission properties.
AB  - High-density, free-standing SiO2 nanowire arrays were successfully fabricated by
      a simple chemical vapor deposition method through a controlled pattern of the
      micrometer-sized alloyed balls on the Si substrate combined with a local balanced
      and steady-state reaction vapor environment. The direct observation of temporal
      evolution of the SiO2 nanowire growth process via the microscopic imaging
      approach offers us amazing pictures related to the unique vapor-liquid-solid
      (VLS) growth styles. These novel results are beneficial to understanding the
      formation mechanism of silica nanowire arrays, and at the same time, they extend
      our knowledge of VLS growth phenomena. The stable and strong ultraviolet emission
      properties of the as-grown products are of significant interest for their
      potential applications related to nanoscale optoelectronic device including
      ultraviolet-light-emitting devices, etc.

PMID- 16898718
TI  - Hierarchical structured Ni nanoring and hollow sphere arrays by morphology
      inheritance based on ordered through-pore template and electrodeposition.
AB  - Fabrication of micro/nano-hierarchical Ni ordered nanostructured arrays is
      demonstrated by electrochemical deposition on the ordered alumina through-pore
      template induced by solution-dipping the colloidal monolayer. The morphology of
      the Ni nanostructured arrays exhibits a ringlike or hollow spherical structure
      depending on the template geometry and appropriate deposition parameters. The
      skeletons of the arrays are of floc- or flakelet-like fine structure on the
      nanoscale. The formation of such morphologies is attributed to the preferential
      growth along the inner wall of the alumina pores, while the nanoflakelet fine
      structure originates from a morphology inheritance process or the transitional
      product Ni(OH)2 which leads to the final nanostructured Ni crystals. This
      morphology inherence could be useful in the field of nanofabrication. Such
      micro/nano-hierarchically structured arrays show good magnetic properties and
      will find applications in the fields of catalysis, magnetics, optoelectrics,
      surface-enhanced Raman scattering (SERS), and new nanodevices.

PMID- 16898719
TI  - Pyrene-terminated phenylenethynylene rigid linkers anchored to metal oxide
      nanoparticles.
AB  - Phenylenethynylene (PE) rigid linkers (para and meta) were used to anchor pyrene
      to the surface of TiO2 (anatase) and ZrO2 nanoparticle thin films through the two
      COOH groups of an isophthalic acid (Ipa) unit. Four chromophore-linker models
      were studied in solution and bound. Two are novel meta-pyrene-PE linker systems:
      dimethyl 5-(3-(1-pyrenylethynyl)phenylethynyl)-isophthalate, carrying one pyrene,
      and dimethyl 5-(bis-3,5-(1-pyrenylethynyl)phenylethynyl)-isophthalate, carrying
      two. These were compared with para rigid-rods dimethyl 5-(1
      pyrenylethynyl)isophthalate and dimethyl 5-(4-(1-pyrenylethynyl)phenylethynyl)
      isophthalate, each carrying one pyrene but varying in length. The length of the
      PE linkers and the para or meta substitution influence the photophysical
      properties of the compounds. The extinction coefficient increased, and the long
      wavelength absorbance of the pyrene chromophore was shifted to the red with
      increasing conjugation. Compared to unsubstituted pyrene, the pyrene-linker
      systems were characterized by short fluorescence lifetimes (tau approximately 2
      ns in tetrahydrofuran solutions), but quantum yields were close to unity. ZINDO/S
      CI calculations attribute this effect to a switching in the order of the two
      lowest-lying singlet states of pyrene. High surface coverages, approximately 10(
      8) mol/cm2, and carboxylate binding modes on nanostructured TiO2 films were
      obtained in all cases. The appearance of a pyrene excimer emission on ZrO2, an
      insulator, indicates that the pyrene-linker system is closely packed (Py-Py < 4
      A) on the surface. The fluorescence emission on TiO2 was completely quenched,
      consistent with quantitative and rapid electron injection into the semiconductor
      indicating that the pyrene excimer acts as a sensitizer. Photoelectrochemical
      studies in regenerative solar cells with I3-/I- as the redox mediator indicated
      near-quantitative conversion of absorbed photons into an electrical current.

PMID- 16898721
TI  - Al2O3:Cr3+ nanotubes synthesized via homogenization precipitation followed by
      heat treatment.
AB  - Cr3+-doped NH4Al(OH)2CO3 nanotubes, templated by surfactant assemblies, were
      successfully synthesized via the homogenization precipitation method, and various
      crystallographic phase Al2O3:Cr3+ nanotubes were also obtained by postannealing
      at different temperatures. The characteristic R1, R2 doublet line transitions of
      ruby can be observed in the high crystalline alpha-Al2O3 nanotubes calcined at
      temperatures higher than 1200 degrees C. The results also indicate that the
      formation mechanism of the tubular nanostructures should result from the self
      rolling action of layered compound NH4Al(OH)2CO3 under the assistance of the
      surfactant soft-template. The convenient synthetic procedure, excellent
      reproducibility, clean reactions, high yield, and fine quality of products in
      this work make the present route attractive and significant. Aluminum oxide
      nanotubes with high specific surface area could be used as fabricating nanosized
      optical devices doped with different elements and stable catalyst supports of
      metal clusters.

PMID- 16898720
TI  - Dependence of DNA electronic structure on environmental and structural
      variations.
AB  - We present experimental and theoretical evidence that varying the local
      environment and physical structure of dried DNA has a direct impact on its
      electronic structure. By preparing samples of DNA in various solutions, it was
      possible to alter the type of ions present during the production of the DNA
      samples. These variations resulted in differences in the local chemical
      environment of the dried DNA molecules. X-ray absorption spectroscopy (XAS) and X
      ray emission spectroscopy (XES) were used to probe the variations in the
      electronic structure of DNA samples. DFT calculations of a stack of 10 adenine
      (A)-thymine (T) nucleobase pairs show that slight structural variations in
      stacking height have a direct influence on the electronic structure and result in
      changes to the HOMO-LUMO gap. The effects of these differences in the local
      environment on the electronic structure are discussed and are related to the
      results of conductivity measurements of DNA.

PMID- 16898722
TI  - Estimation of dielectric function of biotin-capped gold nanoparticles via signal
      enhancement on surface plasmon resonance.
AB  - Biotin-capped gold nanoparticles assembled on flat gold with volume fraction f
      are studied by surface plasmon resonance (SPR) spectroscopy and atomic force
      microscopy (AFM) in order to estimate the dielectric function of the gold
      nanoparticles based on the Maxwell-Garnett (MG) theory. The complex dielectric
      function (epsilon',epsilon'') of the spherical nanoparticles at three
      representative wavelengths in the vis-near-IR region, i.e., lambda = 543, 632.8,
      and 1152 nm, is estimated for a surface homogeneously covered with nanoparticles
      in order to discuss the wavelength dependence of the dielectric function. The SPR
      response of a surface covered with particles in 2D aggregates is also analyzed.
      The experimental SPR curve of the particle aggregates deviates from the
      theoretical predictions, suggesting dipole interactions between particles.

PMID- 16898724
TI  - IR spectra of photopolymerized C60 films. Experimental and density functional
      theory study.
AB  - IR spectra of photopolymerized fullerene films obtained by simultaneous
      deposition and UV irradiation were measured in the range of 1500-450 cm(-1). The
      degree of the polymerization of the C60 films was estimated to be about 95%. To
      assist the assignment of the experimental IR spectra of the films, quantum
      chemical calculations of the equilibrium structures of the C60 dimers and trimers
      were performed at the DFT(B3LYP)/3-21G level of theory. Next, IR frequencies and
      intensities for those structures were calculated. For the five-trimer structures
      found in the calculations, the relative stabilities were determined at the
      B3LYP/4-31G and B3LYP/6-31G levels and used to select the lowest-energy trimers,
      which are Trimer A (angle between monomer centers is 90 degrees ) and Trimer B
      (angle between monomer centers is 120 degrees). Next, the IR spectra of the
      polymerized fullerene films were compared with the calculated frequencies of the
      lowest-energy dimer and the two lowest-energy trimers. On the basis of this
      analysis and on the comparison of the film spectra with the IR spectra of the C60
      dimer and trimer spectra obtained by other methods, it was shown that the main
      components of the films are C60 dimers and the orthorhombic (O) polymer phase.
      The tetragonal (T) and rhombohedral (R) polymers, as well as small amounts of
      monomers, were also found. Although vibrational frequencies of different C60
      phases are similar in most cases, we found several unique spectral features of
      the C60 dimer and other polymers that may be used to determine the composition of
      the polymerized C60 film.

PMID- 16898723
TI  - Controlled one-dimensional nanostructures in poly(3-hexylthiophene) thin film for
      high-performance organic field-effect transistors.
AB  - With the aim of improving the field-effect mobilities in poly(3-hexylthiophene)
      (P3HT) thin film transistors, we controlled the nanostructures of P3HT thin film
      by changing the solvent vapor pressure in a spin-coating chamber during
      solidification. The transistors with P3HT thin films spin-coated under a high
      solvent vapor pressure (56.5 KPa), showing the one-dimensional nanowire
      morphologies, resulted in the relatively high field-effect mobilities (0.02
      cm2/(V.s)) that are typically more than 1 order of magnitude higher than those
      prepared under ambient conditions, showing the featureless morphologies. This can
      be attributed to the higher solvent vapor pressure during film formation,
      providing the solvent is allowed to evaporate slowly and the degree of ordering
      within the P3HT crystalline domains is dramatically improved.

PMID- 16898725
TI  - Mesopore structure of microcrystalline cellulose tablets characterized by
      nitrogen adsorption and SEM: the influence on water-induced ionic conduction.
AB  - Tablets of microcrystalline cellulose were formed at different compaction
      pressures and physical properties, such as pore size distribution, surface area,
      and pore surface fractality, were extracted from N2 adsorption isotherms. These
      properties were compared to previously published data on the water-induced ionic
      conductivity of the tablets. The conduction process was shown to follow a
      percolation model with a percolation exponent of 2 and a porosity percolation
      threshold of approximately 0.1. The critical pore diameter for facilitated charge
      transport was shown to be in the 5-20 nm range. When the network of pores with a
      diameter in this interval is reduced to the point where it no longer forms a
      continuous passageway throughout the compact, the conduction process is dominated
      by charge transport on the surfaces of individual microfibrils mainly situated in
      the bulk of fibril aggregates. A fractal analysis of nitrogen adsorption
      isotherms showed that the dominant interface forces during adsorption is
      attributed to surface tensions between the gas and the adsorbed liquid phase. The
      extracted fractal dimension of the analyzed pore surfaces remained unaffected by
      the densification process at low compaction pressures (< approximately 200 MPa).
      At increased densification, however, pore-surface structures smaller than
      approximately 100 nm become smoother as the fractal dimension decreases from
      approximately 2.5 at high porosities to approximately 2.3 for the densest tablets
      under study.

PMID- 16898726
TI  - Effects of temperature on the alignment and electrooptical responses of a nematic
      nanoscale liquid crystalline film.
AB  - The surface-induced alignment and electrooptical (EO) dynamics of a 50-nm-thick
      liquid crystalline (4-n-pentyl-4'-cyanobiphenyl; 5CB) film were studied at three
      temperatures: 25 and 33 degrees C (near the crystalline-nematic and nematic
      isotropic transition temperatures, respectively) and 29 degrees C (a median
      temperature in the stability region of the nematic phase). The ZnSe surfaces that
      entrap the liquid crystal (LC) film have been polished unidirectionally to
      produce a grooved surface presenting nanometer-scale corrugations, a structure
      that induces a planar and homogeneous orientation in the nematic phase. The
      present work attempts to understand the influences of temperature on the surface
      induced alignment and corresponding EO dynamics of the material. Step-scan time
      resolved spectroscopy measurements were made to determine the rate constants for
      the electric-field-induced orientation and thermal relaxation of the 5CB film.
      The field-driven orientation rates vary sensitively with temperature across a
      range that spans the stability limits of the nematic phase; the relaxation rates,
      however, vary very little across this same temperature range. We propose that
      these differences in LC behavior arise as consequence of the interplay of the
      temperature dependence of the elastic constants, viscosity, and degree of
      orientational order of the LC medium. A simple theoretical model provides some
      understanding of these behaviors.

PMID- 16898727
TI  - Morphological control and luminescent properties of YVO4:Eu nanocrystals.
AB  - Rodlike, olivelike, pineapplelike, and particlelike nanocrystals of theYVO4:Eu (5
      at. % Eu) were synthesized by a hydrothermal reaction with different conditions,
      respectively. The rodlike nanocrystal has a rectangular cross-section with about
      35 x 60 nm2 and a length of about 220 nm. The olivelike nanocrystal has an
      equatorial diameter of approximately 40 nm and a length of approximately 200 nm.
      The pineapplelike nanocrystal with an equatorial diameter of approximately 200 nm
      and a length of approximately 300 nm, is a superstructure consisting of self
      organized nanorods with a diameter of approximately 20 nm and a length of
      approximately 50 nm. The particlelike nanocrystals show globular and polyhedral
      shape with a diameter of approximately 50 nm. Their UV-vis absorption peaks are
      at 305, 308, 285, and 280 nm, respectively, and there is such a trend that the
      absorption peaks shift to higher energy as the size of the particles decreases.
      Compared with other-shape nanocrystals, the luminescence intensity of the
      olivelike nanocrystals is obviously enhanced. It suggests that we could obtain
      the function-improved materials by tailoring the size and shape of theYVO4:Eu
      nanostructures.

PMID- 16898728
TI  - Insights into the self-directed structuring of hybrid organic-inorganic silicas
      through infrared studies.
AB  - Fourier transform infrared (FTIR) spectroscopy has been used to probe the
      organization of the organic fragments in lamellar bridged silsesquioxanes with
      organic substructures based on alkylene chains of various lengths and urea groups
      [O1.5Si(CH2)3NHCONH(CH2)nNHCONH(CH2)3SiO1.5] (n = 6, 8-12). The structure and
      intermolecular interactions (hydrophobic and H-bonding) of these well-defined
      self-structured hybrid silicas are discussed in relation to their powder X-ray
      diffraction patterns. The degree of structural order is determined by the length
      and parity of the alkylene spacer. A concomitant enhancement in the degree of
      condensation of the inorganic component and a decrease in the strength of the
      hydrophobic interactions between the organic components are demonstrated. The
      strength and directionality of the H-bonding are directly correlated to the
      crystalllinity of the organic-inorganic hybrid materials.

PMID- 16898729
TI  - Characterization by 27Al NMR, X-ray absorption spectroscopy, and density
      functional theory techniques of the species responsible for benzene hydrogenation
      in Y zeolite-supported carburized molybdenum catalysts.
AB  - Carburized molybdenum catalysts supported on a dealuminated NaH-Y zeolite were
      prepared by carburization under a 20% methane in hydrogen flow of two precursors
      obtained by adsorption of molybdenum hexacarbonyl, one containing 5 wt % and the
      other 10 wt % Mo, and a third one was prepared by impregnation with aqueous
      ammonium heptamolybdate, containing 5 wt % Mo. The three catalysts displayed very
      distinct behaviors in the benzene hydrogenation reaction at atmospheric pressure
      and 363 K. By using XANES spectroscopy at the molybdenum L edge, EXAFS and XANES
      spectroscopy at the molybdenum K edge, and 27Al solid-state NMR spectroscopy, it
      was shown that different carburized molybdenum species exist in each sample. In
      the catalyst containing 10 wt % Mo, formation of molybdenum carbide nanoparticles
      was observed, with an estimated diameter of 1.8 nm. In the catalyst containing 5
      wt % Mo and prepared by carburization of adsorbed molybdenum hexacarbonyl,
      formation of molybdenum oxycarbide dimers is proposed. In the latter case,
      density functional theory calculations have led to a dimer structure which is
      compatible with EXAFS results. In the catalyst prepared by impregnation with
      ammonium heptamolybdate solution followed by carburization, the molybdenum seems
      to interact with extraframework alumina to produce highly disordered mixed
      molybdenum-aluminum oxycarbides.

PMID- 16898730
TI  - Core-shell and hollow nanocrystal formation via small molecule surface
      photodissociation; Ag@Ag2Se as an example.
AB  - Metallic Ag nanoparticles have been converted to Ag2Se nanoparticles at ambient
      temperature and open atmosphere by UV photodissociation of adsorbed CSe2 on the
      Ag core surface. The photolysis could be prevented at any stage yielding Ag@Ag2Se
      core-shell structures of different thickness. Depending on the initial Ag
      nanoparticle size, either hollow or filled nanocrystals of Ag2Se could be
      prepared. The Kirkendall effect has been proposed to account for the formation of
      hollow nanoparticles. A coated-sphere Drude model has been used to explain the
      redshift of the Ag plasmon band as a function of the Ag2Se shell thickness as
      well as to provide the first estimates of the wavelength-dependent dielectric
      function of Ag2Se. This photochemical method might be especially promising for
      carrying out a direct room-temperature phototransformation of metallic into
      semiconductor nanostructures already assembled on surface templates.

PMID- 16898731
TI  - Thermal stability and thermodynamic properties of hybrid proton-conducting
      polyaryl etherketones.
AB  - The thermal and structural stability of sulfonated cross-linked PEEK (polyether
      ether ketone) and its silicon-containing class II hybrid derivatives were
      characterized by combination of mass spectrometry, infrared spectroscopy, X-ray
      diffraction, thermogravimetric analysis, and differential scanning calorimetry.
      Thermodynamic properties of the hybrids were determined, including glass
      transition temperature, degree of crystallinity, and thermal stability. The
      decomposition processes of the hybrid polymers could be consistently interpreted
      and their energetics quantitatively determined. The introduction of inorganic
      silanol moieties improves the thermal stability compared to sulfonated products.

PMID- 16898732
TI  - Photophysical and photocatalytic properties of SrTiO3 doped with Cr cations on
      different sites.
AB  - Usually, SrTiO3 monodoped with Cr cations at the Ti4+ site hardly shows visible
      light photocatalytic activity. Revealing the origin of this issue is important
      for us to find an alternative approach to make SrTiO3 active under visible light
      irradiation. In this paper, two Cr-doped SrTiO3-(Sr0.95Cr0.05)TiO3 and
      Sr(Ti0.95Cr0.05)O3-were synthesized by a conventional solid-state reaction
      method, and their photophysical and photocatalytic properties were studied
      comparatively. It was found that both (Sr0.95Cr0.05)TiO3 and Sr(Ti0.95Cr0.05)O3
      showed considerable absorption to visible light. However, their photocatalytic
      activities for H2 evolution from aqueous methanol solution under visible light
      irradiation were significantly different: the H2 evolution rate over
      (Sr0.95Cr0.05)TiO3 (approximately 21 micromol/h) was more than 100 times that
      over Sr(Ti0.95Cr0.05)O3 (approximately 0.2 micromol/h). X-ray photoelectron
      spectroscopy analysis results revealed that the Cr cations doped at the Sr2+ site
      were all trivalent state (Cr3+), while those doped at the Ti4+ site were mixed
      valent states (Cr3+ and Cr6+). The different photocatalytic activities of H2
      evolution are supposed to closely relate to the different valent states of Cr
      doped at different sites (Sr2+ or Ti4+) in SrTiO3. Possible electronic structures
      of (Sr0.95Cr0.05)TiO3 and Sr(Ti0.95Cr0.05)O3 were proposed in relation to their
      photophysical and photocatalytic properties.

PMID- 16898733
TI  - In search of fully uncomplexed cyclodextrin in the presence of micellar
      aggregates.
AB  - The chemical behavior of beta-cyclodextrin/nonionic surfactant mixed systems has
      been investigated using the basic hydrolysis of N-methyl-N-nitroso-p
      toluenesulfonamide as a chemical probe. The experimental results prove that at
      the cmc, there are significant quantities of uncomplexed beta-CD in equilibrium
      with the micellar aggregates. In contrast to the expected situation, the
      percentage of uncomplexed beta-CD in equilibrium with the micellar system
      increases on increasing the hydrophobicity of the surfactant molecule. This
      behavior is due to the existence of two simultaneous processes: complexation of
      surfactant monomers by cyclodextrin and the process of self-assembly to form
      micellar aggregates. The autoaggregation of surfactant monomers is expected to be
      more important than the complexation process in this mixed system. Varying the
      hydrophobicity of the surfactant monomer enabled us to determine that the
      percentages of uncomplexed cyclodextrin in equilibrium with the micellar system
      were in the range of 5-95%.

PMID- 16898734
TI  - Theoretical study of long oligothiophene dications: bipolaron vs polaron pair vs
      triplet state.
AB  - A series of oligothiophene dications (from the sexithiophene dication to the 50
      mer oligothiophene dication, nT2+, n = 6-50) were studied. Density functional
      theory (DFT) at the B3LYP/6-31G(d) level and, in some cases, also at BLYP/6-31Gd,
      was applied to study the singlet and triplet states of the whole series. We found
      that the singlet state is the ground state for all oligothiophene dications up to
      the 20-mer, and that the singlet and triplet states are degenerate for longer
      oligomers. Thus, the triplet state is never a pure ground state for these
      dications. We found that, for short oligothiophenes dication (e.g., 6T2+), the
      bipolaron state is the more important state, with only a small contribution made
      by the polaron pair state. For medium size oligothiophene dications (e.g.,
      14T2+), both the bipolaron state and the polaron-pair state contribute to the
      electronic structure. Finally, in long oligothiophene dications, such as 30T2+
      and 50T2+, the contribution from the polaron pair state becomes dominant, and
      these molecules can be considered as consisting of two independent cation
      radicals or a polaron pair. Results from isodesmic reactions show that the
      stability of oligothiophene cation radicals over dications is inversely
      proportional to chain length. Small oligothiophene dications (n = 6-12) were
      studied at the CASSCF(m,m)/6-31G(d) (m = 4, 6, and 10) level. The major
      conclusions of this paper regarding the relative energy of the singlet state
      versus the triplet state and regarding the relative stability of the bipolaron
      versus the polaron pair were also supported by CASSCF calculations.

PMID- 16898735
TI  - ZnO-based hollow microspheres: biopolymer-assisted assemblies from ZnO nanorods.
AB  - Many efforts have been made in fabricating three-dimensional (3D) ordered zinc
      oxide (ZnO) nanostructures due to their growing applications in separations,
      sensors, catalysis, bioscience, and photonics. Here, we developed a new synthetic
      route to 3D ZnO-based hollow microspheres by a facile solution-based method
      through a water-soluble biopolymer (sodium alginate) assisted assembly from ZnO
      nanorods. The products were characterized by X-ray diffraction, field emission
      scanning electron microscopy, transmission electron microscopy, selected area
      electron diffraction, and X-ray photoelectron spectroscopy. Raman and
      photoluminescence spectra of the ZnO-based hollow microspheres were obtained at
      room temperature to investigate their optical properties. The hollow microspheres
      exhibit exciting emission features with a wide band covering nearly all the
      visible region. The calculated CIE (Commission Internationale d'Eclairage)
      coordinates are 0.24 and 0.31, which fall at the edge of the white region (the
      1931 CIE diagram). A possible growth mechanism of the 3D ZnO superstructures
      based on typical biopolymer-crystal interactions in aqueous solution is
      tentatively proposed, which might be really interesting because of the
      participation of the biopolymer. The results show that this biopolymer-directed
      crystal growth and mediated self-assembly of nanocrystals may provide promising
      routes to rational synthesis of various ordered inorganic and inorganic-organic
      hybrid materials with complex form and structural specialization.

PMID- 16898736
TI  - Diffusion NMR as a new method for the determination of the gel point of gelatin.
AB  - The gelation of gelatin has been investigated using pulsed field gradient (PFG)
      NMR. For the first time, diffusion results have been used to determine the
      gelation point, which is indicated by a minimum in the self-diffusion coefficient
      of the free polymer fraction vs temperature. Biexponential analysis of the
      diffusion decay data allowing the diffusion of free and network-bound gelatin to
      be determined separately has been applied to provide an extended insight into the
      gelation process. Low-amplitude oscillatory shear rheology and time-resolved
      dynamic light scattering (DLS) as classical polymer characterization methods were
      applied as control experiments. All three methods yielded a gelation temperature
      of 24-25 degrees C for the cooling regime. Hysteresis effects could also be
      observed.

PMID- 16898737
TI  - Hierarchically structured cobalt oxide (Co3O4): the morphology control and its
      potential in sensors.
AB  - A polyol process was developed to synthesize Co3O4 with controllable
      superstructures. By tuning the reaction conditions, the prepared Co3O4 were
      readily regulated in its morphologies, which could vary from nanosphere to two
      dimensional (2D) nanoplates and 3D hierarchical structures, and finally to
      microspheres. The growth kinetics of such a process was also studied. The
      synthesized Co3O4 exhibited good sensitivity, remarkable selectivity, and high
      stability as an alcohol sensor material.

PMID- 16898738
TI  - The colors of polydiacetylenes: a commentary.
AB  - Polydiacetylenes (PDA) can take several colors, mostly "red" and "blue", and blue
      to-red color transitions are usually considered as transitions from a well
      ordered state to a disordered one. Recent work on single isolated PDA chains
      shows that this is not correct: red chains can be quasi-perfect quantum wires.
      The transition is between two different chain conformations, and each may, or may
      not, be perfectly ordered. Disorder, when it occurs, is a side-product of the
      transformation.

PMID- 16898739
TI  - Modeling steady-state experiments with a scanning electrochemical microscope
      involving several independent diffusing species using the boundary element
      method.
AB  - The BEM algorithm developed earlier for steady-state experiments in the scanning
      electrochemical microscopy (SECM) feedback mode has been expanded to allow for
      the treatment of more than one independently diffusing species. This allows the
      treatment of substrate-generation/tip-collection SECM experiments. The
      simulations revealed the interrelation of sample layout, local kinetics, imaging
      conditions, and the quality of the obtained SECM images. Resolution in the SECM
      SG/TC images has been evaluated, and it depends on several factors. For most
      practical situations, the resolution is limited by the diffusion profiles of the
      sample. When a dissolved compound is converted at the sample (e.g., oxygen
      reduction or enzymatic reaction at the sample), the working distance should be
      significantly larger than in SECM feedback experiments (ca. 3 r(T) for RG = 5) in
      order to avoid diffusional shielding of the active regions on the sample by the
      UME body. The resolution ability also depends on the kinetics of the active
      regions. The best resolution can be expected if all the active regions cause the
      same flux. In one simulated example, which might mimic a possible scenario of a
      low-density protein array, considerable compromises in the resolving power, were
      noted when the flux from two neighboring spots differs by more than a factor of
      2.

PMID- 16898740
TI  - Revisiting acido-basicity of the MgO surface by periodic density functional
      theory calculations: role of surface topology and ion coordination on water
      dissociation.
AB  - Low-coordinated (LC) ions at the MgO surface (noted Mg2+LC and O2-LC with L = 1
      5), located on monatomic and diatomic steps, corners, step divacancies, and
      kinks, have been modeled thanks to periodic density functional theory (DFT)
      calculations (VASP). Ions of lowest coordination induce the strongest surface
      geometry relaxation and the highest surface energies. The hydration energies of
      these sites and thermodynamic stabilities of the resulting surfaces were studied.
      The factors controlling the interaction strength between water and the surface
      are the possibility for the hydroxyl group to adopt a bridging geometry between
      two Mg2+ cations in concave areas of the surface, such as the bottom of the
      monatomic step, and at second order the surface atomic coordination, and
      especially the presence of three-coordinated ions. The Lewis basicity and acidity
      of O2-LC and Mg2+LC, respectively, increase as their coordination number
      decreases, which implies the same trend for the Bronsted basicity of the Mg2+-O2-
      pair toward water. However, this trend can be changed if pairs leading to the
      formation of bridging OH groups are involved, typically on monatomic steps or in
      step divacancies where O2C-H and O3C-H are obtained, respectively, instead of the
      expected O1C-H. Thanks to thermodynamic calculations, the state of the surface as
      a function of temperature can be determined at a given pressure, unraveling the
      roles of surface topology and ions coordination.

PMID- 16898741
TI  - Synchrotron X-ray scattering study of the mechanism of nanopore generation in
      nanoporous organosilicate thin films imprinted with a reactive six-armed porogen.
AB  - In situ grazing incidence small-angle X-ray scattering analysis was successfully
      performed during the thermal processing of film blends of
      polymethylsilsesquioxane (PMSSQ) precursor and triethoxysilyl-terminated six-arm
      poly(epsilon-caprolactone) (mPCL6) porogen. In addition, thermogravimetric
      analysis of the films was carried out in a nitrogen atmosphere. These
      measurements provide important information about the structures of the blend
      films and of the resulting porous films. In particular, they are used in this
      paper to establish the mechanism of the formation of imprinted pores within the
      blend films. During the heating run, the sacrificial thermal degradation of the
      porogen component commenced at 320 degrees C, generating pores in the resulting
      cured PMSSQ films. Only very limited porogen aggregation occurred during the
      blend film formation process (spin-coating and subsequent drying), and these
      porogen aggregates were of relatively small size and narrow size distribution.
      The observed restriction of the formation of such porogen aggregates was found to
      result from the favorable hybridization reaction of the porogen's reactive end
      groups with the reactive functional groups of the PMSSQ precursor, which competes
      with aggregation via reaction between the porogen molecules. The average radius
      (or half-size) of the porogen aggregates was in the range 2.45-3.98 nm, depending
      on the porogen loading (10-40 wt %). The porogen aggregates retained their size
      and size distribution until thermal degradation, which resulted in the imprinting
      of nanopores in the cured PMSSQ films with size and size distribution
      corresponding to those of the porogen aggregates. The porosities of the resulting
      nanoporous films were in the range 12.4-41.7%, depending on the initial porogen
      loading.

PMID- 16898742
TI  - Molecular insights into the heterogeneous crystal growth of si methane hydrate.
AB  - In this paper we report a successful molecular simulation study exploring the
      heterogeneous crystal growth of sI methane hydrate along its [001]
      crystallographic face. The molecular modeling of the crystal growth of methane
      hydrate has proven in the past to be very challenging, and a reasonable framework
      to overcome the difficulties related to the simulation of such systems is
      presented. Both the microscopic mechanisms of heterogeneous crystal growth as
      well as interfacial properties of methane hydrate are probed. In the presence of
      the appropriate crystal template, a strong tendency for water molecules to
      organize into cages around methane at the growing interface is observed; the
      interface also demonstrates a strong affinity for methane molecules. The maximum
      growth rate measured for a hydrate crystal is about 4 times higher than the value
      previously determined for ice I in a similar framework (Gulam Razul, M. S.;
      Hendry, J. G.; Kusalik, P. G. J. Chem. Phys. 2005, 123, 204722).

PMID- 16898743
TI  - Pulsed electrodeposition of two-dimensional Ag nanostructures on Au(111).
AB  - One-step pulsed potential electrodeposition of Ag on Au(111) in the
      underpotential deposition (UPD) region has been studied in 0.5 mM Ag2SO4 + 0.1 M
      H2SO4 aqueous electrolyte at various pulse durations from 0.2 to 500 ms.
      Evolution of the deposited Ag nanostructures was followed by in situ scanning
      tunneling microscopy (STM) and by measurement of the respective current
      transients. At short pulse durations a relatively high number density (4 x 10(11)
      cm(-2)) of two-dimensional Ag clusters with a narrow size and distance
      distribution is observed. They exhibit a remarkably high stability characterized
      by a dissolution potential which lies about 200 mV more anodically than the
      typical potential of Ag-(1 x 1) monolayer dissolution. To elucidate the
      underlying nucleation and growth mechanism, two models have been considered: two
      dimensional lattice incorporation and a newly developed coupled diffusion
      adsorption model. The first one yields a qualitative description of the current
      transients, whereas the second one is in nearly quantitative agreement with the
      experimental data. In this model the transformation of a Ag-(3 x 3) into a Ag-(1
      x 1) structure indicated in the cyclic voltammogram (peaks at 520 vs 20 mV) is
      taken into account.

PMID- 16898746
TI  - Modeling the concentration dependence of the methanol self-diffusivity in
      faujasite systems: comparison with the liquid phase.
AB  - Molecular dynamics simulations were performed to understand further the
      concentration dependence of the self-diffusion of methanol in the faujasite
      zeolite systems. The evolution of the self-diffusivity was investigated as a
      function of coverage for DAY and NaY systems to study the effect of both the pore
      confinement and the presence of the extraframework cations within the supercage.
      It was found that the self-diffusivity decreases with loading for DAY, whereas
      for NaY it passes through a maximum at intermediate coverage, in agreement with
      pulse-field gradient NMR and quasi elastic neutron scattering data reported in
      similar systems. The activation energies of the methanol diffusion corresponding
      to a combination of both intra- and intercage motions were evaluated as a
      function of the coverage. The simulated trends are interpreted on the basis of
      the predominant interactions which take place in both systems. Finally, the
      preferential arrangement of the adsorbate molecules are provided and compared
      with those simulated in the liquid phase. For the fully loaded materials, it was
      seen that the methanol molecules form a one-dimensional hydrogen-bonded chain
      along the channels in DAY whereas only dimers are present in NaY.

PMID- 16898744
TI  - Atomic structures of benzene and pyridine on Si(5 5 12)-2 x 1.
AB  - The adsorption structures of benzene and pyridine on Si(5 5 12)-2 x 1 were
      studied at 80 K by using a low-temperature scanning tunneling microscope and
      density functional theory calculations. These structures are different from those
      observed on low-index Si surfaces: benzene molecules exclusively bind to two
      adatoms, that is, with di-sigma bonds between carbon atoms and silicon adatoms,
      leading to the loss of benzene aromaticity; in contrast, pyridine molecules
      interact with adatom(s) through either Si-N dative bonding or di-sigma bonds.
      Dative bonding configurations with pyridine aromaticity are the dominant
      adsorption features and are more stable than di-sigma bonding configurations.
      Thus the dative bonding of nitrogen-containing heteroaromatic molecules provides
      a strategy for the controlled attachment of aromatic molecules to high-index
      surfaces.

PMID- 16898745
TI  - Carbon monoxide adsorption and oxidation on monolayer films of cubic platinum
      nanoparticles investigated by infrared-visible sum frequency generation
      vibrational spectroscopy.
AB  - The adsorption and oxidation of CO on monolayer films of cubic Pt nanoparticles
      synthesized by a modified solution-phase polyol process were examined by sum
      frequency generation (SFG) vibrational spectroscopy in total internal reflection
      (TIR) geometry. Extremely low incident laser power (approximately 5 microJ/pulse
      of infrared) yields sufficient SFG intensity in TIR geometry and reduces
      destructive interference. Because TIR-SFG spectroscopy does not require
      correction for bulk gas absorption, CO spectra can be collected over a wide
      pressure range (<1 mTorr up to 700 Torr). Poly(vinylpyrrolidone)-capped Pt
      nanoparticles deposited on single-crystal sapphire were monitored under high
      pressure reaction conditions in a combined spectroscopy-catalytic reactor cell.
      The effect of the capping polymer on the position and intensity of the CO peak
      was studied before and after low-temperature calcination. The polymer decreased
      the amount of CO adsorption and caused a slight red-shift of the atop CO band
      relative to a surface treated in oxygen at 373 K. Oxidation rates were determined
      by measuring the intensity of the atop CO peak as a function of time in the
      presence of flowing oxygen. The activation energy (approximately 19.8 kcal/mol)
      determined from the SFG data is close to that obtained from gas chromatography
      (GC) measurements of CO oxidation rates at different temperatures. The SFG and GC
      results are in good agreement with published data for Pt(100) surfaces.

PMID- 16898747
TI  - Dye-sensitized solar cells based on anatase TiO2 nanoparticle/nanowire
      composites.
AB  - Dye-sensitized solar cells were fabricated based on the composites of anatase
      TiO2 nanoparticles and single crystalline anatase TiO2 nanowires.
      Nanoparticle/nanowire composites can possess the advantages of both building
      blocks, i.e., the high surface area of nanoparticle aggregates and the rapid
      electron transport rate and the light scattering effect of single-crystalline
      nanowires. Three different composites were prepared with 5 wt %, 20 wt %, and 77
      wt % nanowires, respectively. The performances of composite solar cells were
      compared with pure nanoparticle cells at a series of film thickness. With low
      nanowire concentrations (5 wt % and 20 wt %), the composite films maintain
      similar specific surface area as the pure nanoparticle films, while the composite
      cells show higher short-circuit current density and open-circuit voltage. An
      enhancement of power efficiency from 6.7% for pure nanoparticle cells to 8.6% for
      the composite cell with 20 wt % nanowires has been achieved under 1 Sun AM1.5
      illumination (100 mW/cm2). For the composite film with 77 wt % nanowires, the
      nanowires became the major phase. Their less compact packing resulted in
      significant decrease of the specific surface area, and thus the current density.
      However, with the increase of film thickness, the current density showed a
      continuous increase in the whole thickness range up to 17 microm, indicating the
      improved electron diffusion length due to the formed nanowire network. The
      nanowires also helped to preserve crack-free thick films. These results show that
      employing nanoparticle/nanowire composites represents a promising approach for
      further improving the efficiencies of sensitized solar cells.

PMID- 16898748
TI  - Propensity for the air/water interface and ion pairing in magnesium acetate vs
      magnesium nitrate solutions: molecular dynamics simulations and surface tension
      measurements.
AB  - Molecular dynamics simulations in slab geometry and surface tension measurements
      were performed for aqueous solutions of magnesium acetate and magnesium nitrate
      at various concentrations. The simulations reveal a strong affinity of acetate
      anions for the surface, while nitrate exhibits only a very weak surface
      propensity, and magnesium is per se strongly repelled from the air/water
      interface. CH3COO- also exhibits a much stronger tendency than NO3- for ion
      pairing with Mg2+ in the bulk and particularly in the interfacial layer. The
      different interfacial behavior of the two anions is reflected by the opposite
      concentration dependence (beyond 0.5 M) of surface tension of the corresponding
      magnesium salts. Measurements, supported by simulations, show that the surface
      tension of Mg(NO3)2(aq) increases with concentration as for other inorganic
      salts. However, in the case of Mg(OAc)2(aq) the surface tension isotherm exhibits
      a turnover around 0.5 M, after which it starts to decrease, indicating a positive
      net solute excess in the interfacial layer at higher concentrations.

PMID- 16898749
TI  - Electrowetting of aligned carbon nanotube films.
AB  - Electrowetting is one approach to reducing the interfacial tension between a
      solid and a liquid. In this method, an electrical potential is applied across the
      solid/liquid interface which modifies the wetting properties of the liquid on the
      solid without changing the composition of the solid and liquid phases.
      Electrowetting of aligned carbon nanotube (CNT) films is investigated by the
      sessile drop method by dispensing deionized (DI) water or 0.03 M NaCl droplets
      (contacted by Au wire) onto aligned CNT films assembled on a copper substrate.
      The results demonstrate that electrowetting can greatly reduce the hydrophobicity
      of the aligned CNTs; the contact angle saturation for DI water and 0.03 M NaCl
      droplets occurs at 98 and 50 degrees , respectively. The combined effects of the
      geometrical roughness and the electrical potential on the contact angle are
      briefly discussed and modeled. Such a strategy may be invoked to controllably
      reduce the interfacial tension between carbon nanotubes (CNTs) and polymer
      precursors when infiltrating the monomers into the prealigned nanotube films.

PMID- 16898750
TI  - Structural changes in self-assembled monolayers initiated by ultraviolet light.
AB  - Self-assembled monolayers of 2-anthracenethiol and 2-naphthalenethiol on gold
      (111) were irradiated with low-power UV light. Scanning tunneling microscope
      images recorded in situ show unusual structural changes. In the case of 2
      anthracenethiol, structures measuring 4-7 nm wide and 30-40 nm in length are
      formed. Images taken 10 min after irradiation ceased to show further surface
      reorganization. With 2-naphthalenethiol SAMs, smaller structures form upon
      irradiation, which subsequently revert to resemble the original structure after
      time.

PMID- 16898752
TI  - Classical molecular dynamics study of [60]fullerene interactions with silica and
      polyester surfaces.
AB  - This study examines the interaction of neutral and charged fullerenes with model
      silica and polyester surfaces. Molecular dynamics simulations at 298 K indicate
      that van der Waals forces are sufficiently strong in most cases to cause
      physisorption of the neutral fullerene particle onto the surfaces. The fullerenes
      are unable to penetrate the rigid silica surface but are generally able to at
      least partially infiltrate the flexible polymer surface by opening surface
      cavities. The introduction of charge to the fullerene generally leads to an
      increase in both the separation distance and Work of Separation with silica.
      However, the charged fullerenes generally exhibit significantly closer and
      stronger interactions with polyester films, with a distinct tendency to absorb
      into the "bulk" of the polymer. The separation distance and Work of Separation of
      C60 with each of the surfaces also depend greatly on the sign, magnitude, and
      localization of the charge on the particle. Cross-linking of the polyester can
      improve resistance to the neutral fullerene. Functionalization of the polyester
      surface (F and OH substituents) has been shown to prevent the C60 from
      approaching as close to the polyester surface. Fluorination leads to improved
      resistance to positively charged fullerenes, compared to the unmodified
      polyester. However, hydroxylation generally enables greater adhesion of charged
      fullerenes to the surface due to H-bonding and electrostatic attraction.

PMID- 16898753
TI  - Comparison of ribonucleic acid homopolymer ionization energies and charge
      injection barriers.
AB  - Thin films of guanosine and uridine ribonucleic acid (RNA) homopolymers (poly rG,
      poly rU) were grown in high vacuum in several steps on highly oriented pyrolytic
      graphite (HOPG) using electrospray deposition. Between deposition steps, the
      sample surface was characterized with X-ray and ultraviolet photoemission
      spectroscopy (XPS, UPS). The resulting spectra series allowed the determination
      of the orbital alignment at the HOPG interface, as well as the ionization
      energies of the homopolymer thin films. Comparison with earlier results on
      cytidine and adenosine RNA homopolymers (poly rC, poly rA) indicates significant
      ionization energy and charge injection barrier differences between purines and
      pyrimidines.

PMID- 16898754
TI  - Partial oxidation of propene on oxygen-covered Au(111).
AB  - Partial oxidation of propene is promoted by Au following deposition of atomic
      oxygen (0.3 ML) via O3 decomposition on Au(111) at 200 K. Several partial
      oxidation products--acrolein, acrylic acid, and carbon suboxide (O=C=C=C=O)-are
      produced in competition with combustion to CO2 and H2O. Acrolein is the primary
      partial oxidation product, and it is further oxidized to the other products by
      excess oxygen. We propose that acrolein is derived from allyloxy intermediate
      that is formed via insertion of oxygen into the allylic C-H bond. While no
      propene epoxide formation is detected from oxidation of C3H6, a small amount of
      epoxidation is observed during reaction of C3D6 and CD3CH=CH2. These results are
      strong indications that small changes in the energy required for allylic C-H
      activation, in this case due to a kinetic isotope effect, may dramatically change
      the selectivity; thus, small modifications of the properties of oxygen on Au may
      lead to the more desirable epoxidation process. Our results are discussed in the
      context of the origin of activity of Au-based catalysts.

PMID- 16898751
TI  - Rate of interfacial electron transfer through the 1,2,3-triazole linkage.
AB  - The rate of electron transfer is measured to two ferrocene and one iron
      tetraphenylporphyrin redox species coupled through terminal acetylenes to azide
      terminated thiol monolayers by the Cu(I)-catalyzed azide-alkyne cycloaddition (a
      Sharpless "click" reaction) to form the 1,2,3-triazole linkage. The high yield,
      chemoselectivity, convenience, and broad applicability of this triazole formation
      reaction make such a modular assembly strategy very attractive. Electron-transfer
      rate constants from greater than 60,000 to 1 s(-1) are obtained by varying the
      length and conjugation of the electron-transfer bridge and by varying the
      surrounding diluent thiols in the monolayer. Triazole and the triazole carbonyl
      linkages provide similar electronic coupling for electron transfer as esters. The
      ability to vary the rate of electron transfer to many different redox species
      over many orders of magnitude by using modular coupling chemistry provides a
      convenient way to study and control the delivery of electrons to multielectron
      redox catalysts and similar interfacial systems that require controlled delivery
      of electrons.

PMID- 16898755
TI  - Novel method for the synthesis of hydrophobic Pt-Ru nanoparticles and its
      application to preparing a Nafion-free anode for the direct methanol fuel cell.
AB  - Pt-Ru alloy is a bimetallic catalyst most commonly used in the direct methanol
      fuel cell (DMFC). In this paper, a new process to synthesize an unsupported Pt-Ru
      colloid has been introduced. The characteristics of synthesized nanoparticles
      were identified by XRD, TEM/EDX, and SEM, and it shows that Ru atoms are
      incorporated into the Pt fcc structure and the well-dispersed particles (diameter
      approximately 4 nm) possess a Pt-rich feature. This catalyst shows a hydrophobic
      characteristic which can adsorb very well on the hydrophobic-treated carbon paper
      or carbon cloth without the need of Nafion. Accordingly, this method can avoid
      particle agglomeration, and the synthesized catalyst demonstrates strong
      adsorption with carbon paper. In addition, this colloid-type Nafion-free catalyst
      was measured via linear sweep voltammetry (LSV) and exhibited electrochemical
      activity for methanol oxidation comparable to the commercial one with Nafion
      binding.

PMID- 16898756
TI  - Rh-promoted methanol decomposition on cerium oxide thin films.
AB  - Methanol adsorption and reaction have been studied on Rh-deposited cerium oxide
      thin films under UHV conditions using temperature-programmed desorption and
      synchrotron soft X-ray photoelectron spectroscopy. The methanol behavior was
      examined as a function of the Ce oxidation state, methanol exposure, and Rh
      particle size and coverage. When Rh nanoparticles were deposited on the ceria
      films, methanol decomposed on Rh to CO and H below 200 K. H atoms recombined and
      desorbed between 200 and 300 K. CO evolved from Rh deposited on fully oxidized
      ceria between 400 and 500 K. However, on reduced ceria films, the CO on Rh
      further decomposed to atomic C. Methanol adsorbed on the ceria films deprotonated
      to form methoxy as the only intermediate on the surface. This methoxy decomposed
      and desorbed as CO and H2 at higher temperatures regardless of the ceria
      oxidation state. Compared with the methanol reaction on Rh-free ceria thin films,
      formaldehyde formation from methoxy was completely suppressed after Rh
      deposition. Our results indicate that Rh can promote the decomposition of methoxy
      adsorbed on the ceria and that decomposition of methoxy intermediates occurred at
      the metal/oxide interfaces. On the other hand, the reduced ceria can promote
      total methanol decomposition on Rh.

PMID- 16898757
TI  - Characterization of iron promoter in tungstated zirconia catalysts by Mossbauer
      spectroscopy at very low temperatures.
AB  - A tungstated zirconia (WZ) catalyst with iron promoter used for the conversion of
      n-pentane into isopentane has been characterized by Mossbauer spectroscopy. The
      Mossbauer spectra have been recorded in zero magnetic field in the temperature
      range 0.05-295 K and with a magnetic field up to 7 T between 4.2 and 50 K. Both
      the recording of Mossbauer spectra with an applied magnetic field and at
      extremely low temperature allowed for the demonstration that iron is present in
      the catalysts as (i) hematite (alpha-Fe2O3) particles a few 10 nm in size, (ii)
      very small oligomeric Fe(III) species, probably in solid solution in zirconia,
      and (iii) Fe(III) oxide clusters showing magnetic ordering, probably embedded in
      the first surface layer and thus forming "rafts". These latter clusters form two
      ensembles with quite different sizes: one with diameters of about 3 nm, the other
      with diameters larger than 30 nm. These results are in agreement with those
      recently obtained by X-ray absorption spectroscopy and electron paramagnetic
      resonance.

PMID- 16898758
TI  - Room-temperature isolation of V(benzene)2 sandwich clusters via soft-landing into
      n-alkanethiol self-assembled monolayers.
AB  - The adsorption state and thermal stability of V(benzene)2 sandwich clusters soft
      landed onto a self-assembled monolayer of different chain-length n-alkanethiols
      (Cn-SAM, n = 8, 12, 16, 18, and 22) were studied by means of infrared reflection
      absorption spectroscopy (IRAS) and temperature-programmed desorption (TPD). The
      IRAS measurement confirmed that V(benzene)2 clusters are molecularly adsorbed and
      maintain a sandwich structure on all of the SAM substrates. In addition, the
      clusters supported on the SAM substrates are oriented with their molecular axes
      tilted 70-80 degrees off the surface normal. An Arrhenius analysis of the TPD
      spectra reveals that the activation energy for the desorption of the supported
      clusters increases linearly with the chain length of the SAMs. For the longest
      chain C22-SAM, the activation energy reaches approximately 150 kJ/mol, and the
      thermal desorption of the supported clusters can be considerably suppressed near
      room temperature. The clear chain-length-dependent thermal stability of the
      supported clusters observed here can be explained well in terms of the cluster
      penetration into the SAM matrixes.

PMID- 16898759
TI  - Conformational equilibrium of 1,2-dichloroethane in water: comparison of PCM and
      RISM-SCF methods.
AB  - The RISM-SCF and polarizable continuum model (PCM) approaches have been applied
      to study the conformational equilibrium of 1,2-dichloroethane (DCE) in water.
      Both the electron correlation effect and basis sets play an important role in the
      relative energies of the gauche and trans conformers in gas and solution phases.
      Both PCM and RISM-MP2 methods resulted in a consistent trend with the previous
      experimental and theoretical studies that the population of the gauche conformer
      increases in going from the gas phase to the aqueous solution. However, the PCM
      treatment could not describe the solvent effect completely in that the sign of
      the relative free energy of the gauche and trans forms is opposite to the most
      recent experimental and theoretical data, while the RISM-MP2 gives the right sign
      in the free energy difference. We found that the larger excess chemical potential
      gain (by ca. -4.1 kcal/mol) for the gauche conformer is large enough to result in
      the gauche preference of DCE in water, though it has to compensate for more
      solute reorganization energy (approximately 1.6 kcal/mol) and overcome the energy
      difference (approximately 1.6 kcal/mol) in the gas phase. The radial distribution
      functions between DCE and the nearest water shows that the electrostatic
      repulsion between chlorine and oxygen atoms is higher in the trans conformer than
      in the gauche one, while the attractive interaction between chlorine and hydrogen
      of water is higher in the gauche conformer.

PMID- 16898760
TI  - An adiabatic linearized path integral approach for quantum time-correlation
      functions II: a cumulant expansion method for improving convergence.
AB  - Linearized mixed quantum-classical simulations are a promising approach for
      calculating time-correlation functions. At the moment, however, they suffer from
      some numerical problems that may compromise their efficiency and reliability in
      applications to realistic condensed-phase systems. In this paper, we present a
      method that improves upon the convergence properties of the standard algorithm
      for linearized calculations by implementing a cumulant expansion of the relevant
      averages. The effectiveness of the new approach is tested by applying it to the
      challenging computation of the diffusion of an excess electron in a metal-molten
      salt solution.

PMID- 16898761
TI  - Kinetics of strain-induced structural changes under high pressure.
AB  - A mechanism-based microscale kinetic theory for strain-induced structural changes
      (SCs) (that includes phase transformations (PTs) and chemical reactions (CRs)) is
      developed. Time is not an independent parameter in this theory; instead, plastic
      strain is a time-like parameter. Kinetics depends essentially on the ratio of the
      yield strengths of phases. Stationary and nonstationary solutions of the kinetic
      equations are analyzed for various cases, including SCs between two phases in an
      inert matrix and between three phases in silicon and germanium. A number of
      experimental phenomena are explained, and material parameters controlling the
      kinetics of strain-induced SCs are determined. This includes the possibility of
      intensification (or suppression) of SCs at the initial stage of straining by
      adding a stronger (or weaker) inert phase, zero pressure hysteresis that however
      has nothing to do with phase equilibrium pressure, the possibility of obtaining
      some phases (that cannot be obtained under hydrostatic loading) under strains,
      and the possibility to obtain some phases under relatively small shear, which
      disappear under larger shear.

PMID- 16898762
TI  - Molecular dynamics simulation of structure, thermodynamic, and dynamic properties
      of poly(dimethylsilamethylene), poly(dimethylsilatrimethylene) and their
      alternating copolymer.
AB  - Molecular dynamics is used for the simulation of silicon-containing polymers with
      promising membrane material properties. An atomistic force field is developed for
      the description of bond bending, torsional angle variation, and nonbonded intra-
      and intermolecular interactions. Detailed ab initio quantum mechanics
      calculations on corresponding monomers that appeared recently in the literature
      are used for the parametrization of the bonded and nonbonded local intramolecular
      force field. For the intermolecular and nonbonded nonlocal intramolecular
      interactions, parameters are obtained from accurate force fields proposed in the
      literature for similar compounds. The force field is used subsequently for the
      calculation of thermodynamic, structure, and dynamic properties of two
      homopolymers, namely, poly(dimethylsilamethylene) and
      poly(dimethylsilatrimethylene), and their alternating copolymer. A wide range of
      temperatures and pressures is examined. Polymer systems of different molecular
      weights are simulated. Experimental data available for these polymers are very
      limited. In all cases, simulation results are in good agreement with these data.
      Furthermore, simulation results agree very well with empirical macroscopic
      correlations used widely for rubbery polymers for the properties under
      consideration.

PMID- 16898763
TI  - Phase diagrams of binary crystalline-crystalline polymer blends.
AB  - A thermodynamically self-consistent theory has been developed to establish binary
      phase diagrams for two-crystalline polymer blends by taking into consideration
      all interactions including amorphous-amorphous, crystal-amorphous, amorphous
      crystal, and crystal-crystal interactions. The present theory basically involves
      combination of the Flory-Huggins free energy for amorphous-amorphous isotropic
      mixing and the Landau free energy of polymer solidification (e.g.,
      crystallization) of the crystalline constituents. The self-consistent solution
      via minimization of the free energy of the mixture affords determination of
      eutectic, peritectic, and azeotrope phase diagrams involving various coexistence
      regions such as liquid-liquid, liquid-solid, and solid-solid coexistence regions
      bound by liquidus and solidus lines. To validate the present theory, the
      predicted eutectic phase diagrams have been compared with the reported
      experimental binary phase diagrams of blends such as polyethylene fractions as
      well as polycaprolactone/trioxane mixtures.

PMID- 16898765
TI  - On the accuracy of force fields for predicting the physical properties of
      dimethylnitramine.
AB  - The accuracy of three force fields for predicting the physical properties of
      dimethylnitramine (DMNA) has been investigated by using molecular dynamics
      simulations. The Sorescu, Rice, and Thompson (SRT) (J. Phys. Chem. B 1997, 101,
      798) rigid-molecule, flexible generalized AMBER (J. Comput. Chem. 2004, 25,
      1157), and Smith et al. flexible force fields (J. Phys. Chem. B 1999, 103, 705)
      were tested. The density, lattice parameters, isotherm, and melting point of DMNA
      are calculated using classical molecular dynamics. Except for the melting point,
      the predictions of the three force fields are in reasonable agreement with
      experimental values. The calculated thermodynamic melting points (Tmp) for the
      SRT, AMBER, and Smith et al. force fields are 380, 360, and 260 K, respectively.
      The experimental value is 331 K. Modifications of the torsional barriers in the
      AMBER force field resulted in Tmp = 346 K, in good agreement with the
      experimental value of 331 K. The calculated lattice parameters and bulk modulus
      are also improved with the modifications of the AMBER potential. The results
      indicate that, although not sufficiently accurate without modifications, the
      general force fields such as AMBER provide the basis for developing force fields
      that correctly predict the physical properties of nitramines.

PMID- 16898764
TI  - Aqueous solvation free energies of ions and ion-water clusters based on an
      accurate value for the absolute aqueous solvation free energy of the proton.
AB  - Thermochemical cycles that involve pKa, gas-phase acidities, aqueous solvation
      free energies of neutral species, and gas-phase clustering free energies have
      been used with the cluster pair approximation to determine the absolute aqueous
      solvation free energy of the proton. The best value obtained in this work is in
      good agreement with the value reported by Tissandier et al. (Tissandier, M. D.;
      Cowen, K. A.; Feng, W. Y.; Gundlach, E.; Cohen, M. J.; Earhart, A. D.; Coe, J. V.
      J. Phys. Chem. A 1998, 102, 7787), who applied the cluster pair approximation to
      a less diverse and smaller data set of ions. We agree with previous workers who
      advocated the value of -265.9 kcal/mol for the absolute aqueous solvation free
      energy of the proton. Considering the uncertainties associated with the
      experimental gas-phase free energies of ions that are required to use the cluster
      pair approximation as well as analyses of various subsets of data, we estimate an
      uncertainty for the absolute aqueous solvation free energy of the proton of no
      less than 2 kcal/mol. Using a value of -265.9 kcal/mol for the absolute aqueous
      solvation free energy of the proton, we expand and update our previous
      compilation of absolute aqueous solvation free energies; this new data set
      contains conventional and absolute aqueous solvation free energies for 121
      unclustered ions (not including the proton) and 147 conventional and absolute
      aqueous solvation free energies for 51 clustered ions containing from 1 to 6
      water molecules. When tested against the same set of ions that was recently used
      to develop the SM6 continuum solvation model, SM6 retains its previously
      determined high accuracy; indeed, in most cases the mean unsigned error improves
      when it is tested against the more accurate reference data.

PMID- 16898766
TI  - Sensitivity enhancement and heteronuclear distance measurements in biological 17O
      solid-state NMR.
AB  - In this contribution we present a comprehensive approach to study hydrogen
      bonding in biological and biomimetic systems through 17O and 17O-1H solid-state
      NMR combined with density functional theory calculations of 17O and 1H NMR
      parameters. We explore the signal enhancement of 17O in L-tyrosine.HCl using
      repetitive double-frequency swept radio frequency pulses in solid-state NMR. The
      technique is compatible with high magnetic fields and fast magic-angle spinning
      of the sample. A maximum enhancement by a factor of 4.3 is obtained in the signal
      to-noise ratio of the selectively excited 17O central transition in a powdered
      sample of 17Oeta-L-tyrosine.HCl at an external field of 14.1 T and a spinning
      frequency of 25 kHz. As little as 128 transients lead to meaningful 17O spectra
      of the same sample at an external field of 18.8 T and a spinning frequency of 50
      kHz. Furthermore we employed supercycled symmetry-based pulse sequences on the
      protons to achieve heteronuclear longitudinal two-spin-order (IzSz) recoupling to
      determine 17O-1H distances. These sequences recouple the heteronuclear dipolar
      17O-1H couplings, where dipolar truncation is absent, while decoupling the
      homonuclear proton dipolar interactions. They can be applied at fast magic-angle
      spinning frequencies up and beyond 50 kHz and are very robust with respect to 17O
      quadrupolar couplings and both 17O and 1H chemical shift anisotropies, which
      makes them suitable for the use at high external magnetic fields. The method is
      demonstrated by determining the 17Oeta-1H distance in L-tyrosine.HCl at a
      spinning frequency of 50 kHz and an external field of 18.8 T.

PMID- 16898767
TI  - Molecular interactions between estrogen receptor and its ligand studied by the ab
      initio fragment molecular orbital method.
AB  - The ab initio fragment molecular orbital calculations were performed for
      molecular interactions of the whole estrogen receptor (ER) ligand-binding domain
      with a natural ligand, 17beta-estradiol (EST). The interaction energies of the
      ligand at the residue level were calculated using HF and MP2 methods with several
      basis sets. The charge-transfer (CT) interactions were also analyzed based on
      configuration analysis for fragment interaction. Strong electrostatic
      interactions were observed between the EST and surrounding charged/polarized
      residues, Glu353, Arg394, His524, and Thr347. Weak electrostatic and significant
      van der Waals dispersion interactions were observed between the EST and the many
      surrounding hydrophobic residues. Together with the experimental interpretations,
      both interactions equally contributed to the total binding energies, and it was
      found that the inclusion of electron correlation was essential to obtain an
      appropriate picture of the interaction. The strongest interaction energy was
      observed between Glu353 and the EST, and the CT interactions from the lone-pair
      orbital of the carbonyl oxygen of Glu353 to the sigma(OmicronEta) orbital of the
      hydroxyl group of EST were found to be important. The CT interactions from the
      lone-pair orbital of EST to the sigma(NuEta) of Arg394 and from the lone-pair
      orbital of EST to the sigma(NuEta) of His524 were also observed. These CT
      interactions occurred through the hydrogen-bond networks between the ER and EST.
      Therefore, electron donations from the ER to the EST and electron back-donations
      from EST to the ER were characteristic of ER-ligand binding. Our approach
      provides a powerful tool to understanding detailed molecular interactions at the
      quantum mechanical level.

PMID- 16898768
TI  - Infrared multiphoton dissociation spectroscopic analysis of peptides and
      oligosaccharides by using fourier transform ion cyclotron resonance mass
      spectrometry with a midinfrared free-electron laser.
AB  - The fragmentation of peptides and oligosaccharides in the gas phase was
      investigated by means of electrospray ionization Fourier transform ion cyclotron
      resonance (FTICR) mass spectrometry coupled with dissociation by a laser-cleavage
      infrared multiphoton dissociation (IRMPD) technique. In this technique, an IR
      free-electron laser is used as a tunable source of IR radiation to cause cleavage
      of the ionized samples introduced into the FTICR cell. The gas-phase IRMPD
      spectra of protonated peptides (substance P and angiotensin II) and two sodiated
      oligosaccharides (sialyl Lewis X and lacto-N-fucopentaose III) were obtained over
      the IR scan range of 5.7-9.5 microm. In the IRMPD spectra for the peptide,
      fragment ions are observed as y/b-type fragment ions in the range 5.7-7.5 microm,
      corresponding to cleavage of the backbone of the parent amino acid sequence,
      whereas the spectra of the oligosaccharides have major peaks in the range 8.4-9.5
      microm, corresponding to photoproducts of the B/Y type.

PMID- 16898769
TI  - Protein secondary structure controlled with light and photoresponsive
      surfactants.
AB  - The interaction of a light-responsive azobenzene surfactant with bovine serum
      albumin (BSA) has been investigated as a means to examine photoreversible changes
      in protein secondary structure. The cationic azobenzene surfactant undergoes a
      reversible photoisomeriztion upon exposure to the appropriate wavelength of
      light, with the visible-light (trans) form being more hydrophobic and, thus,
      inducing a greater degree of protein unfolding than the UV-light (cis) form.
      Fourier transform infrared (FT-IR) spectroscopy is used to provide quantitative
      information on the secondary structure elements in the protein (alpha-helices,
      beta-strands, beta-turns, and unordered domains). Comparing the secondary
      structure changes induced by light illumination in the presence of the
      photoresponsive surfactant with previous measurements of the tertiary structure
      of BSA obtained from small-angle neutron scattering (SANS) allows the three
      discrete conformation changes in BSA to be fully characterized. At low surfactant
      concentrations, an alpha-helix --> beta-structure rearrangement is observed as
      the tertiary structure of BSA changes from a heart-shaped to a distorted heart
      shaped conformation. Intermediate surfactant concentrations lead to a dramatic
      decrease in the alpha-helix fraction in favor of unordered structures, which is
      accompanied by an unfolding of the C-terminal portion of the protein as evidenced
      from SANS. Further increases in photosurfactant concentration lead to a beta -->
      unordered transition with the protein adopting a highly elongated conformation in
      solution. Each of these protein conformational changes can be precisely and
      reversibly controlled with light illumination, as revealed through FT-IR spectra
      collected during repeated visible-light <--> UV-light cycles.

PMID- 16898771
TI  - Intercalation of ethidium into triple-strand poly(rA).2poly(rU): a thermodynamic
      and kinetic study.
AB  - The kinetics and equilibria of the interaction of ethidium bromide (EB) with the
      triple-stranded RNA, poly(rA).2poly(rU), have been investigated by stopped-flow,
      absorption, fluorescence, and circular dichroism methods; to properly assess the
      effect of the third strand on the polymer molar properties, molar volumes,
      adiabatic compressibilities, and heats of melting have also been measured for
      both poly(rA).2poly(rU) and poly(rA).poly(rU). The melting experiments reveal
      that ethidium tends to destabilize the triplex, whereas it stabilizes the duplex;
      however, the triplex/ethidium system in 0.1 M NaCl is stable below 37 degrees C.
      The static titrations reveal that one ethidium ion binds every three base
      triplets of the polymer; on the basis of the excluded-site model, this feature
      suggests intercalation, as in the duplex, but the binding affinity for the
      triplex is weaker compared to that for the duplex. The kinetic experiments
      displayed a two-phase behavior, which was rationalized assuming the sequence D +
      S right arrow over left arrow DS(I), DS(I) + S right arrow over left arrow DS(II)
      + S (D = drug, S = site), the second step involving direct transfer of the drug
      between strands. Comparison with the duplex/EB system reveals that the additional
      strand of poly(U), present in the triplex, hinders the formation of the
      intermediate complex DS(I), while stabilizing the structure of the final DS(II)
      complex by hampering the partial slipping out of the dye from the triplex cavity.

PMID- 16898770
TI  - Nonphotochemical hole-burning study of selectively stained normal and cancerous
      human ovarian tissues.
AB  - Results are presented of nonphotochemical hole-burning (HB) experiments on
      cancerous ovarian and analogous normal peritoneal in vitro tissues stained with
      the mitochondrial-selective dye rhodamine 800. A comparison of fluorescence
      excitation spectra, hole-growth kinetics data, and external electric field
      (Stark) effects on the shape of spectral holes burned in cancerous and normal
      tissues stained with rhodamine 800 revealed significant differences only in the
      dipole moment change (fDeltamu) measured by a combination of HB and Stark
      spectroscopies. It is shown that the permanent dipole moment change for the S0-->
      S1 transition of the rhodamine 800 molecules in cancerous tissue is higher than
      that of normal tissue by a factor of about 1.4. The finding is similar to the HB
      results obtained earlier for human ovarian surface epithelial cell lines, i.e.,
      OV167 carcinoma and OSE(tsT)-14 normal cells stained with the same mitochondria
      specific dye (Walsh et al. Biophys. J. 2003, 84, 1299). We propose that the
      observed difference in the permanent dipole moment change in cancerous ovarian
      tissue is related to a modification in mitochondrial membrane potential.

PMID- 16898772
TI  - The effect of salt stoichiometry on protein-salt interactions determined by
      ternary diffusion in aqueous solutions.
AB  - We report the four diffusion coefficients for the lysozyme-MgCl2-water ternary
      system at 25 degrees C and pH 4.5. The comparison with previous results for the
      lysozyme-NaCl-water ternary system is used to examine the effect of salt
      stoichiometry on the transport properties of lysozyme-salt aqueous mixtures. We
      find that the two cross-diffusion coefficients are very sensitive to salt
      stoichiometry. One of the cross-diffusion coefficients is examined in terms of
      common-ion, excluded-volume, and protein-preferential hydration effects. We use
      the four ternary diffusion coefficients to extract chemical-potential cross
      derivatives and protein-preferential interaction coefficients. These
      thermodynamic data characterize the protein-salt thermodynamic interactions. We
      demonstrate the presence of the common-ion effect (Donnan effect) by analyzing
      the dependence of the preferential-interaction coefficient not only with respect
      to salt concentration but also with respect to salt stoichiometry. We conclude
      that the common-ion effect and the protein-preferential hydration are both
      important for describing the lysozyme-MgCl2 thermodynamic interaction.

PMID- 16898776
TI  - Synthesis and characterization of glucosamine-bound near-infrared probes for
      optical imaging.
AB  - [structure: see text] Two novel near-infrared (NIR) fluorescent probes have been
      synthesized by linking a carbocyanine fluorophore and glucosamine through
      different linkers. These probes demonstrated a high quantum yield, low
      cytotoxicity, reversible pH-dependent fluorescence in the physiological pH range,
      and a decreased aggregation tendency in aqueous solutions. In vitro NIR optical
      imaging studies revealed cellular uptake and strong intracellular NIR
      fluorescence of these two probes in four breast epithelial cell lines.

PMID- 16898773
TI  - The micro-optical ring electrode. 3: Transient photocurrent studies of
      photophysical-electrochemical and photophysical-chemical-electrochemical systems.
AB  - The micro-optical ring electrode (MORE) is a photoelectrochemical device based on
      a ring microelectrode that uses the insulating material interior to the ring
      electrode as a light guide. In this paper, we describe the preparation and
      characterization of very thin ring MOREs with (ring inner radius)/(ring outer
      radius) > 0.99. Theoretically, we derive asymptotic analytical expressions for
      the time dependence of the diffusion-limited transient light-on photocurrent
      generated by two general types of photoelectrochemical systems: (a) the PE
      (photophysical-electrochemical) system, wherein the photoexcited species itself
      is directly detected on the ring; (b) the PCE (photophysical-chemical
      electrochemical) system, wherein the photoexcited species undergoes a homogeneous
      electron transfer reaction prior to electrochemical detection. Experimentally, we
      establish that it is possible to use such MOREs to study the wavelength
      dependence of photocurrents derived from photoelectrochemically active systems,
      such as the Ru(bipy)3 2+/Fe3+ PCE system, demonstrating the potential utility of
      the MORE as a selective electroanalytical probe. We also use our expressions for
      the time dependence of photocurrents at the MORE to derive values for the
      photoelectrochemical kinetic parameters of this system, including the rate
      coefficient for the back reaction of photogenerated Ru(bipy)3 3+ (0.115 s(-1))
      and the quantum efficiency for the primary redox products, Ru(bipy)3 3+ and Fe2+,
      escaping cage recombination, phi(CE) = 0.099.

PMID- 16898777
TI  - Ruthenium-catalyzed alkylative lactonization and carbocyclization.
AB  - [reaction: see text] The cationic ruthenium complex [CpRu(NCCH3)3]PF6 promotes
      the coupling of monosubstituted allene carboxylic acids and simple alpha,beta
      unsaturated olefins to form five- and six-membered lactones. The mild reaction
      conditions allow for the presence of various functional groups.

PMID- 16898778
TI  - Systematic errors in computed alkane energies using B3LYP and other popular DFT
      functionals.
AB  - [structure: see text] Energies computed by B3LYP and other popular DFT
      functionals are flawed by systematic errors, which can become considerable for
      larger molecules. These errors, predominately due to inadequacies in assessing
      longer-range nonbonded attractive effects (dispersion), are illustrated by the
      isodesmic stabilization energies of n-alkanes (based on methane and ethane, which
      have no stabilizing 1,3-alkyl group interactions). Newer functionals, designed to
      describe weak interactions, give somewhat better agreement with experiment, but
      are not fully satisfactory.

PMID- 16898779
TI  - Many density functional theory approaches fail to give reliable large hydrocarbon
      isomer energy differences.
AB  - [structure: see text] Several DFT methods were found to be unreliable for
      computing hydrocarbon isomer energy differences. The errors grow with system size
      up to 20 kcal mol(-1) for the relative energies of the (CH)12 isomers;
      octahedrane is the most stable (CH)12 hydrocarbon. While DFT geometries generally
      are good, problems arise for structures with single bonds only, especially for
      small rings. We recommend the use of higher level, non-DFT energy single points
      computed at DFT-optimized structures.

PMID- 16898780
TI  - Click chemistry as a reliable method for the high-density postsynthetic
      functionalization of alkyne-modified DNA.
AB  - [reaction: see text] We report the development of the Cu(I)-catalyzed Huisgen
      cycloaddition (click) reaction for the multiple postsynthetic labeling of alkyne
      modified DNA. A series of alkyne-modified oligodeoxyribonucleotides (ODNs) of
      increasing alkyne density were prepared, and the click reaction using various
      azide labels was investigated. Complete high-density conversion was observed for
      ODNs containing up to six consecutive alkyne functions. Compatibility of the
      click conditions with long DNA strands was shown using a PCR product obtained
      with an alkyne-modified primer.

PMID- 16898781
TI  - Theoretical rationale for regioselection in phosphine-catalyzed allenoate
      additions to acrylates, imines, and aldehydes.
AB  - [reaction: see text] A rationale for regioselection in phosphine-promoted
      annulations of acrylates, imines, and aldehydes with allenoates has been
      developed using computation at the B3LYP/6-31G(d) level of theory. The computed
      transition states revealed that Lewis acid activation, strong hydrogen bonding (H
      bonding), and minimization of unfavorable van der Waals contacts are the guiding
      factors responsible for regioselection. An excellent level of correlation between
      the calculated regioselectivities and experiment was observed.

PMID- 16898782
TI  - Asymmetric multicomponent [C+NC+CC] synthesis of highly functionalized
      pyrrolidines catalyzed by silver(I).
AB  - [reaction: see text] Highly functionalized pyrrolidines are obtained in a single
      chemical step via a mild, efficient, and selective Ag(I)-catalyzed asymmetric
      [C+NC+CC] coupling process. Oppolzer's camphorsultam enables the desired reaction
      cascade and provides a reliable means to control the developing stereochemistry
      and purify the products. This three-component reaction provides unprecedented
      access to structurally diverse pyrrolidines for both target- and diversity
      oriented syntheses.

PMID- 16898783
TI  - Probing selectivity in recognition-mediated dynamic covalent processes.
AB  - [reaction: see text] Two simple recognition-mediated dynamic Diels-Alder systems
      are used to probe the role of kinetics and thermodynamics in determining the
      equilibrium position in exchanging libraries and the time taken to reach that
      equilibrium. The selectivity expressed by recognition-driven dynamic processes is
      demonstrated to be less than the free-energy difference between the components as
      a result of compensatory effects arising from the extent of conversion to
      products within the library.

PMID- 16898784
TI  - Enantio- and diastereoselective allylmetalations: an easy and efficient access to
      the AB spiroketal of spongistatin.
AB  - [reaction: see text] A unique combination of highly enantio- and
      diastereoselective allylmetalations and a one-pot
      "desacetalization/spiroketalization" have been employed to synthesize the AB
      spiroketal fragment (C1-C13) of spongistatin in 15 steps and in excellent
      diastereoselectivity.

PMID- 16898785
TI  - Total synthesis of (+/-)-magnofargesin.
AB  - [reaction: see text] A convenient method for the preparation of 2,5-dihydrofurans
      by using the chemistry of alkynyl(phenyl)iodonium salts is reported. Treatment of
      3-alkoxy-1-alkynyl(phenyl)iodonium triflates with sodium benzenesulfinate
      generates an alkylidenecarbene, which undergoes [1,5]-C-H insertion to form 2
      substituted 4-benzenesulfonyl-2,5-dihydrofurans in reasonable yield. These cyclic
      vinyl sulfones are functionalized in such a way as to make them useful starting
      materials for the preparation of lignans. The application of this methodology to
      the first total synthesis of (+/-)-magnofargesin is disclosed.

PMID- 16898786
TI  - Approach to the synthesis of cladiell-11-ene-3,6,7-triol.
AB  - [reaction: see text] The synthesis of an advanced intermediate in the synthesis
      of the title compound has been achieved. Key steps include an Ireland-Claisen
      rearrangement to install the C7 tertiary alcohol stereocenter, an SN2' reaction
      of an alkoxymethyl Cu reagent, and a diastereoselective Re-catalyzed allylic
      alcohol transposition.

PMID- 16898787
TI  - Synthetic studies toward the bryostatins: a substrate-controlled approach to the
      A-ring.
AB  - [reaction: see text] The synthesis of a C1-C13 A-ring subunit of bryostatin 1 is
      detailed. The key features of the approach include the convergent fragment
      assembly with a highly stereoselective construction of the C7-C8 bond indicated
      above.

PMID- 16898788
TI  - Hybrid polyoxotungstates as second-generation POM-based catalysts for microwave
      assisted H2O2 activation.
AB  - [structure: see text] Organic-inorganic hybrids synthesized from lacunary
      polyoxotungstates (POMs) have been screened as oxidation catalysts with H2O2
      under MW irradiation. Yields up to 99% have been obtained in 25-50 min depending
      both on the POM structure and on the organic moiety. The reaction scope,
      optimized with the best performing catalyst [gamma-SiW10O36(PhPO)2]4-, includes
      epoxidation of terminal and internal double bonds, alcohol oxidation, and
      sulfoxidation, as well as oxygen transfer to electron-deficient substrates as
      chalcone, ketones, and sulfoxides.

PMID- 16898790
TI  - A convenient synthesis of 4-alkyl-5-aminoisoxazoles.
AB  - [reaction: see text] A series of 4-alkyl-5-aminoisoxazoles have been synthesized
      in high yield by nucleophilic addition of lithiated alkyl nitriles to (alpha)
      chlorooximes. The scope and limitations of this reaction were examined by varying
      the nature of the nitrile and chloride oxime.

PMID- 16898789
TI  - A convenient and genuine equivalent to HZrCp2Cl generated in situ from ZrCp2Cl2
      DIBAL-H.
AB  - [reaction: see text] Slow addition of 1 equiv of (i)Bu2AlH to ZrCp2Cl2 in THF
      provides a convenient route to either HZrCp2Cl-(i)Bu2AlCl (Reagent I) or HZrCp2Cl
      (Reagents II and III). The latter represents a highly convenient route to genuine
      HZrCp2Cl, while Reagent I is useful for regio- and stereoselective conversion of
      1- and 2-alkynes into (E)-1-iodo-1-alkenes and (E)-2-iodo-2-alkenes,
      respectively.

PMID- 16898791
TI  - Synthesis and characterization of dicyanovinyl-substituted thienylpyrroles as new
      nonlinear optical chromophores.
AB  - [structure: see text] New dicyanovinyl-substituted 1-(alkyl)aryl-2-(2'
      thienyl)pyrroles 2 were synthesized and characterized. The solvatochromic
      behavior of the synthesized compounds was investigated. All the derivatives
      showed reversible oxidation and reduction on the CV time scale. The
      hyperpolarizabilities (beta) of compounds 2 were measured using hyper-Rayleigh
      scattering. The results are among the highest beta values reported for donor
      acceptor-substituted thienylpyrroles.

PMID- 16898792
TI  - G-quartet formation from an N2-modified guanosine derivative.
AB  - [structure: see text] We report G-quartet formation from an N2-modified
      lipophilic guanosine nucleoside, N2-(4-n-butylphenyl)-2',3',5'-O
      triacetylguanosine. We show that, in the presence of either K+ or Na+, this
      guanosine derivative self-assembles into a D4-symmetric octamer consisting of two
      stacking all-syn G-quartets in a tail-to-tail (or head-to-head) fashion and a
      central ion.

PMID- 16898793
TI  - Total syntheses of (+/-)-beta-erythroidine and (+/-)-8-oxo-beta-erythroidine by
      an intramolecular Diels-Alder cycloaddition of a 2-amidoacrolein.
AB  - [reaction: see text] The total syntheses of (+/-)-beta-erythroidine and (+/-)-8
      oxo-beta-erythroidine are described. The tetracyclic ring system of the natural
      products was quickly assembled by a strategy that features a
      retrocycloaddition/cycloaddition reaction of an amidodioxin, an intramolecular
      Heck reaction, and a 6pi-electrocyclic ring closure of a dienoic acid.

PMID- 16898794
TI  - 1,6-Stannatropic strategy: effective generation and cyclization of 1,5-dipoles
      from o-stannylmethylated thioanilides or phenyl isothiocyanates.
AB  - [reaction: see text] A new method for the generation of 1,5-dipoles from o
      stannylmethylated thioanilides via 1,6-stannatropy under neutral conditions was
      developed. Cyclization of the 1,5-dipoles afforded indole derivatives
      effectively. The strategy has potential for application to the generation of
      alternative 1,5-dipoles from o-stannylmethylated aryl isothiocyanates leading to
      indole derivatives having a stannylthio group that was readily converted to other
      functional groups.

PMID- 16898795
TI  - Allosteric regulation of the conformational dynamics of a cavitand receptor.
AB  - [reaction: see text] Inspired by allostery in nature, we synthesized cavitand 1
      and investigated regulation of its conformational dynamics. Quantitative 1H NMR
      studies have revealed that the rate of the conformational isomerization of 1 can
      be modulated using the external addition of acid. As 1 maintains its vase-like
      conformation in an acidic environment, ample opportunities for controlling the
      kinetics of molecular recognition, and thus reactivity, in this and related
      receptors have arisen.

PMID- 16898796
TI  - Facile synthesis of complicated 9,9-diarylfluorenes based on BF3.Et2O-mediated
      Friedel-Crafts reaction.
AB  - [reaction: see text] BF3.OEt2-mediated Friedel-Crafts reaction of 9-phenyl
      fluoren-9-ol with electron-rich aromatic substrates to prepare a new family of
      complicated 9,9-diarylfluorenes is described. The 9,9-diarylfluorenes tethered
      with various functional substituents, e.g., bulky spiro units, hole-transporting
      moieties, and fluorescent dyes, will be promising building blocks for the
      construction of optoelectronic materials.

PMID- 16898797
TI  - 2-(Trimethylsilyloxy)furan as a dianion equivalent: a two-step synthesis of
      functionalized spirocyclic butenolides.
AB  - [reaction: see text] The use of 2-(trimethylsilyloxy)furan derivatives as dianion
      equivalents leads to a general and connective spiroannulation protocol for the
      efficient preparation of spirocyclic butenolides.

PMID- 16898798
TI  - Practical beta-lactone synthesis: epoxide carbonylation at 1 atm.
AB  - [reaction: see text] A readily prepared bimetallic catalyst is capable of
      effecting epoxide carbonylation to produce beta-lactones at substantially lower
      CO pressures than previously reported catalyst systems. A functionally diverse
      array of beta-lactones is produced in excellent yields at CO pressures as low as
      1 atm. This procedure allows for epoxide carbonylation on a multigram scale
      without the requirement of specialized, high-pressure equipment.

PMID- 16898800
TI  - Efficient metal-catalyzed hydroarylation of styrenes.
AB  - [reaction: see text] A highly efficient metal-catalyzed hydroarylation of various
      styrenes has been developed. This new bismuth-catalyzed C-H functionalization
      provides straightforward access to a series of valuable 1,1-diarylalkane
      products.

PMID- 16898799
TI  - Fluorescent organic nanoparticles of benzofuran-naphthyridine linked molecules:
      formation and fluorescence enhancement in aqueous media.
AB  - [structure: see text] Ethynyl-linked benzofuran-naphthyridine compounds show high
      yield fluorescence with solvatochromic properties. One of the compounds, ABAN,
      has successfully formed fluorescent organic nanoparticles (FONs), for which the
      photophysical properties such as the spectral features and intensity are
      remarkably different from those at the molecular level (solution) and in bulk
      material. The results are tentatively rationalized by the FONs inducing
      coplanarization of the benzofuran-naphthyridine molecule to extend its effective
      conjugation length and hence increase the oscillator strength.

PMID- 16898801
TI  - A series of polyamide receptor based PET fluorescent sensor molecules: positively
      cooperative Hg2+ ion binding with high sensitivity.
AB  - [structure: see text] A series of PET fluorescent sensor molecules were designed
      and synthesized based on BODIPY fluorophore and polyamide receptors. Comparison
      of the photophysical properties of these sensor molecules, equipped with di-, tri
      , and tetraamide receptor, provided a deep insight into the polyamide-Hg2+
      interactions, and an unusual positively cooperative tetraamide-Hg2+ complexation
      was disclosed. In addition, sensor S3 displayed several favorable sensing
      properties.

PMID- 16898802
TI  - Microwaves make hydroformylation a rapid and easy process.
AB  - [reaction: see text] Hydroformylation of alkenes can be carried out in a few
      minutes under microwave activation at a relatively low pressure (40 psi) using
      commercially available catalysts and ligands. The 80 mL vial of a Discover
      microwave oven was connected to a cylinder of CO and H2, and after filling the
      reactor at 40 psi, a mixture of an alkene, the Wilkinson catalyst, and XANTPHOS
      was submitted to microwave irradiation giving, after 4 min, high conversion into
      the corresponding aldehyde without formation of the isomerized alkene.

PMID- 16898803
TI  - Diastereoselective cobalt-catalyzed reductive aldol cyclizations using
      diethylzinc as the stoichiometric reductant.
AB  - [reaction: see text] Cobalt catalysis enables a new method for the generation of
      zinc enolates using diethylzinc to reduce alpha,beta-unsaturated amides. This
      method has been applied to a high-yielding diastereoselective reductive aldol
      cyclization.

PMID- 16898804
TI  - All-carbon-substituted vinylsilane stable to TBAF: synthesis of
      allyldimethylvinylsilane and its Pd-catalyzed cross-coupling under mild
      conditions.
AB  - [reaction: see text] Allyldimethylvinylsilanes 3 are easily synthesized by the
      reaction of silylallylmetals, generated from 1 by n-BuLi/t-BuOK, with carbonyl
      compounds in the absence or presence of metal halides. They can tolerate 2 equiv
      of TBAF in THF at room temperature for at least 6 h but can be easily activated
      in the presence of a palladium catalyst and TBAF to perform the cross-coupling
      reaction with aryl iodides at room temperature.

PMID- 16898805
TI  - Chemo- and regioselective functionalization of uracil derivatives. Applications
      to the synthesis of oxypurinol and emivirine.
AB  - [reaction: see text] A novel route for the synthesis of 4,5-difunctionalized
      uracils using a chemo- and regioselective bromine/magnesium exchange reaction on
      5-bromo-4-halogeno-2,6-dimethoxypyrimidines has been developed. Applications to
      the synthesis of pharmaceuticals such as oxypurinol and emivirine are reported.

PMID- 16898806
TI  - Preparation of aryl-alkylamines via electrophilic amination of functionalized
      arylazo tosylates with alkylzinc reagents.
AB  - [reaction: see text] A new electrophilic amination reaction of functionalized
      arylazo tosylates with alkylzinc halides or dialkylzinc reagents in THF leads to
      the corresponding hydrazines. A facile cleavage of the N-N bond is achieved using
      Raney nickel in refluxing ethanol, leading to substituted secondary aryl
      alkylamines in 45-79% yield.

PMID- 16898807
TI  - Intermolecular reactions of chlorohydrine anions: acetalization of carbonyl
      compounds under basic conditions.
AB  - [reaction: see text] Nonenolizable aldehydes and ketones react with 2
      chloroethanol and 3-chloropropanol under basic conditions (t-BuOK, DMF/THF) with
      formation of 2-substituted 1,3-dioxolanes and 1,3-dioxanes, respectively.
      Conversion of the two-step addition-alkylation process depends on the
      electrophilicity of the carbonyl group that governs the equilibrium of addition
      of chloroalkoxides. This method of protection of carbonyl groups in the form of
      cyclic acetals under kinetically controlled conditions is complementary to the
      acid-catalyzed reaction with diols.

PMID- 16898809
TI  - C6-substituted analogues of 8-azanebularine: probes of an RNA-editing enzyme
      active site.
AB  - [reaction: see text] We describe the synthesis of derivatives of 8-azanebularine,
      a known inhibitor of adenosine deaminases including the RNA-editing enzyme ADAR2.
      6-Methyl, 6-hydroxymethyl, 6-cyano, and 6-mercapto derivatives were obtained from
      6-bromo precursors using different cross-coupling or substitution reactions. The
      C6-methyl derivative was incorporated into an RNA substrate for ADAR2 via the
      phosphoramidite. Quantitative gel mobility shift experiments with the resulting
      RNA indicate that methylation at C6 dramatically reduces the affinity of 8
      azanebularine for ADAR2.

PMID- 16898808
TI  - Avinosol, a meroterpenoid-nucleoside conjugate with antiinvasion activity
      isolated from the marine sponge Dysidea sp.
AB  - [structure: see text] The new meroterpenoids avinosol (1), 3'-aminoavarone (2),
      and 3'-phenethylaminoavarone (3) have been isolated from the marine sponge
      Dysidea sp. collected in Papua New Guinea, and their structures were elucidated
      by analysis of spectroscopic data. Avinosol (1), which is apparently the first
      example of a naturally occurring meroterpenoid-nucleoside conjugate, showed
      antiinvasion activity in a cell-based assay.

PMID- 16898810
TI  - Total synthesis of (+/-)-hasubanonine.
AB  - [reaction: see text] Total synthesis of the alkaloid (+/-)-hasubanonine is
      described. A key feature of the route is generation of a phenanthrene
      intermediate via a Suzuki coupling-Wittig olefination-ring-closing metathesis
      sequence. Conversion of the phenanthrene into the target molecule required six
      steps including dearomatization by means of oxidative phenolic coupling, anionic
      oxy-Cope rearrangement, and a final acid-promoted cyclization. Production of an
      undesired rearranged product in the last step could be suppressed by moderating
      the acid strength.

PMID- 16898811
TI  - trans-hydroalumination/alkylation: one-pot synthesis of trisubstituted allylic
      alcohols.
AB  - [reaction: see text] Described herein is a method of stereoselective synthesis of
      trisubstituted allylic alcohols by alkylation of alkenyl alanates, formed in situ
      through treatment of propargyl alcohols with Vitride (Red-Al). This technique
      represents the first of its kind to feature a trans-hydrometalation, and is
      particularly effective for the formation of 1,4-dienes. Applications involving
      primary, secondary, and tertiary alcohols are discussed, as well as limitations
      regarding both alkyne and electrophile components.

PMID- 16898812
TI  - Synthesis and optical and electrochemical properties of core-fluorinated perylene
      bisimides.
AB  - [reaction: see text] A series of bay position difluoro- or tetrafluoro
      substituted perylene bisimides have been synthesized by nucleophilic halogen
      exchange reaction of the corresponding dibromo- and tetrachloro-substituted
      perylene bisimides, respectively, with potassium fluoride. Compared to the parent
      unsubstituted perylene bisimides, these compounds display hypsochromically
      shifted absorption and fluorescence spectra with fluorescence quantum yields up
      to unity enabling bright yellow emission. Their electrochemical properties and
      crystal structures of two perylene bisimides are also reported.

PMID- 16898813
TI  - Regioselective carbolithiation of o-amino-(E)-stilbenes: cascade route to the
      quinoline scaffold.
AB  - [reaction: see text] The regioselective carbolithiation of substituted ortho
      amino-(E)-stilbenes can be exploited to initiate cascade reaction sequences that
      can be utilized as new routes to substituted 3,4-dihydro-1H-quinolin-2-ones,
      1,2,3,4-tetrahydroquinolines, 1,4-dihydroquinolines, and quinolines.

PMID- 16898814
TI  - Versatile and practical chiral shift reagent with hydrogen-bond donor/acceptor
      sites in a macrocyclic cavity.
AB  - [structure: see text] Bifunctional macrocycle 1 with C2 symmetry was newly
      synthesized. NMR studies demonstrated that receptor 1 functions as a chiral shift
      reagent (solvating agent) that is highly effective for a wide range of chiral
      compounds having a carboxylic acid, oxazolidinone, lactone, alcohol, sulfoxide,
      sulfoximine, isocyanate, or epoxide functionality. Binding constants were
      determined to investigate the binding behavior of 1.

PMID- 16898815
TI  - Synthesis and cross-coupling reactions of 7-azaindoles via a new donor-acceptor
      cyclopropane.
AB  - [reaction: see text] A new type of donor-acceptor cyclopropane has been prepared
      from commercially available cyclopropane-1,1-diesters. This cyclopropane reacts
      with triflic anhydride to produce an isolable tristrifloxy intermediate which
      when treated with primary amines gives 6-trifloxy-7-azaindolines which in turn
      can be dehydrogenated to the azaindoles. The 6-trifloxy substituent can be used
      to introduce diversity at this position via a variety of cross-coupling reactions
      thus preparing potentially interesting compounds based on the important 7
      azaindole pharmacophore.

PMID- 16898816
TI  - Stereodivergent approach to the asymmetric synthesis of bacillariolides: a formal
      synthesis of ent-bacillariolide II.
AB  - [reaction: see text] Asymmetric synthesis of densely functionalized bicyclic
      frameworks for entry into bacillariolides I/III and ent-bacillariolide II is
      reported. The key features are ring-closing metathesis of a pair of
      diastereomerically related dienes obtained through a stereodivergent route from a
      R-(+)-glyceraldehyde derivative, transformation of a nonstereoselective
      cyclopentene ester enolate alkylation process to a completely stereoselective one
      through alkylation of a bulky ester enolate with a bulky electrophile, and a
      remote silyloxymethyl group directed epoxidation.

PMID- 16898817
TI  - Efficient N-heterocyclic carbene-catalyzed O- to C-acyl transfer.
AB  - [reaction: see text] An N-heterocyclic carbene promotes the rearrangement of
      alpha-amino acid derived O-acyl carbonates to their corresponding C-acylated
      isomers, generating a C-C bond and a quaternary stereocenter with high
      efficiency, under mild reaction conditions and with low catalyst loadings.

PMID- 16898818
TI  - New efficient organic activators for highly enantioselective reduction of
      aromatic ketones by trichlorosilane.
AB  - [reaction: see text] Aryl ketones were reduced to the corresponding alcohols with
      excellent enantioselectivity (up to 99.7% ee) by Cl3SiH in the presence of a
      catalytic amount of N-formyl-alpha'-(2,4,6-triethylphenyl)-L-proline as an
      activator. Both carboxyl group at the alpha-position of the activator and 2,4,6
      triethylphenyl group at the alpha'-position were critical for the high
      enantioselectivity.

PMID- 16898819
TI  - Enantiospecific approach toward pentalenolactone.
AB  - [reaction: see text] The enantiospecific assembly of the pentalenolactones'
      carbon skeleton was achieved in 17 steps and 16% overall yield from methyl alpha
      D-glucopyranoside. The synthetic strategy relies on two highly efficient key
      steps: an exo-diastereoselective Diels-Alder reaction and a nonsymmetric
      ozonolysis.

PMID- 16898821
TI  - Platinum-catalyzed intramolecular asymmetric hydroarylation of unactivated
      alkenes with indoles.
AB  - [reaction: see text] A 1:1 mixture of the platinum bis(phosphine) complex [(S)
      4]PtCl2 [(S)-4 = (S)-3,5-t-Bu-4-MeO-MeOBIPHEP] catalyzes the intramolecular
      asymmetric hydroarylation of 2-(4-pentenyl)indoles in moderate to good yield with
      up to 90% ee.

PMID- 16898820
TI  - Sulfamidation of 2-arylaldehydes and ketones with chloramine-T.
AB  - [reaction: see text] A series of aliphatic and aromatic carbonyl compounds has
      been transformed into the corresponding sulfamidated products by means of amine
      catalyzed nitrene transfer of chloramine-T. Depending on the residues R, either
      alpha-sulfamidation in the case of aromatic aldehydes and acetone derivatives or
      direct sulfamidation at the carbonyl functionality of aliphatic aldehydes has
      been observed. Applying microwave conditions, good to excellent yields under
      significantly reduced reaction times could be obtained, thus providing a facile
      access to alpha,alpha-disubstituted amino acids.

PMID- 16898822
TI  - Facile one-pot synthesis of N-difluoromethyl-2-pyridone derivatives.
AB  - [reaction: see text] A novel one-pot synthesis of N-difluoromethyl-2-pyridones is
      described. N-(Pyridin-2-yl)acetamide derivatives were excellent precursors for
      the preparation of N-difluoromethyl-2-pyridone derivatives. Difluoromethylation
      of 2-acetaminopyridine derivatives was achieved with sodium chlorodifluoroacetate
      as a difluorocarbene source in the presence of a catalytic amount of 18-crown-6.
      Subsequent in situ hydrolysis of resultant 1,2-dihydro-2-acetimino-1
      difluoromethylpyridines proceeded under mild acidic conditions to afford the
      corresponding N-difluoromethyl-2-pyridones in moderate to good yields.

PMID- 16898823
TI  - Development of a one-pot asymmetric azaelectrocyclization protocol: synthesis of
      chiral 2,4-disubstituted 1,2,5,6-tetrahydropyridines.
AB  - [reaction: see text] A one-pot procedure for tetracyclic chiral aminoacetals, the
      useful precursors for substituted piperidine synthesis, has been established via
      Stille-Migita coupling, 6pi-azaelectrocyclization, and aminoacetal formation from
      readily prepared vinylstannanes, vinyliodides, and cis-aminoindanol derivatives.
      Based on the method, chiral 2,4-disubstituted 1,2,5,6-tetrahydropyridines,
      bearing a variety of aromatic substituents at the C-2 position, have been
      prepared.

PMID- 16898824
TI  - Synthesis of 2,4,6-trisubstituted chiral piperidines and (-)-dendroprimine by one
      pot asymmetric azaelectrocyclization protocol.
AB  - [reaction: see text] Stereocontrolled synthesis of 2,4,6-trisubstituted
      piperidine diastereomers has been realized from common intermediates, obtained by
      a one-pot azaelectrocyclization protocol. Based on the method, the asymmetric
      synthesis of an indolizidine alkaloid, (-)-dendroprimine, was achieved.

PMID- 16898825
TI  - Enantioselective alkylation of aldehydes catalyzed by a highly active titanium
      complex of 3-substituted unsymmetric BINOL.
AB  - [reaction: see text] A titanium complex derived from 3-(3,5-diphenylphenyl)-BINOL
      exhibits an enhanced catalytic activity in the asymmetric alkylation of
      aldehydes, allowing the reduction of the catalyst amount to less than 1 mol %
      without deterioration in enantioselectivity.

PMID- 16898826
TI  - Rapid assembly of matrix metalloprotease inhibitors using click chemistry.
AB  - [reaction: see text] A panel of 96 metalloprotease inhibitors was assembled using
      "click chemistry" by reacting eight zinc-binding hydroxamate warheads with 12
      azide building blocks. Screens of the bidentate compounds against representative
      metalloproteases provided discerning inhibition fingerprints, revealing compounds
      with low micromolar potency against MMP-7. The relative ease and convenience of
      the strategy in constructing focused chemical libraries for rapid in situ
      screening of MMPs is thereby demonstrated.

PMID- 16898827
TI  - Novel seco-dibenzopyrrocoline alkaloid from Cryptocarya oubatchensis.
AB  - [structure: see text] A novel seco-dibenzopyrrocoline alkaloid, named
      oubatchensine 6, and five phenanthroindolizidines (1-5) were isolated from
      Cryptocarya oubatchensis, and their structures were elucidated. Displacement
      centrifugal partition chromatography was used to purify compounds 1 and 6.
      Structure determination of the latter was carried out by mass spectrometry, NMR
      spectroscopy, quantum chemistry, and computer-assisted structure determination.
      Cytotoxic activity against KB cells was then investigated.

PMID- 16898828
TI  - Total synthesis of jimenezin via an intramolecular allylboration.
AB  - [structure: see text] An efficient total synthesis of the annonaceous acetogenin
      jimenezin was achieved. The key steps used were a highly stereoselective
      intramolecular allylboration to establish the tetrahydropyran ring and an
      intramolecular Williamson reaction to close the tetrahydrofuran ring.

PMID- 16898829
TI  - Generation of N-acyliminium ions via intramolecular conjugate addition reactions:
      a strategy for the total synthesis of nakadomarin A.
AB  - [reaction: see text] The rapid construction of the tetracyclic core ring system
      of nakadomarin A via a tandem enecarbamate Michael addition/N-acyliminium ion
      cyclization is described.

PMID- 16898831
TI  - pH- and H2O-driven triple-mode pyrene fluorescence.
AB  - [reaction: see text] A simple-structured molecule L1, a diethylenetriamine
      bearing two end pyrene fragments, demonstrates triple-mode fluorescence
      consisting of monomer and short- and long-lived excimer emissions in water, which
      are precisely controlled by pH and an addition of a less-polar organic solvent.

PMID- 16898830
TI  - Iron(III)-promoted aza-Prins-cyclization: direct synthesis of six-membered
      azacycles.
AB  - [reaction: see text] A new iron(III) halide-promoted aza-Prins cyclization
      between gamma,delta-unsaturated tosylamines and aldehydes provides six-membered
      azacycles in good to excellent yields. The process is based on the consecutive
      generation of gamma-unsaturated-iminium ion and further nucleophilic attack by
      the unsaturated carbon-carbon bond. Homoallyl tosylamine leads to trans-2-alkyl-4
      halo-1-tosylpiperidine as the major isomer. In addition, the alkyne aza-Prins
      cyclization between homopropargyl tosylamine and aldehydes gives 2-alkyl-4-halo-1
      tosyl-1,2,5,6-tetrahydropyridines as the only cyclic products.

PMID- 16898832
TI  - Turrapubesins A and B, first examples of halogenated and maleimide-bearing
      limonoids in nature from Turraea pubescens.
AB  - [structure: see text] Two novel tetranortriterpenoids, turrapubesins A (1) and B
      (2), representing the first examples of halogenated and maleimide-bearing
      limonoids, were isolated from the twigs and leaves of Turraea pubescens. The
      structures of 1 and 2 were elucidated by extensive spectroscopic analysis. Their
      absolute configurations were determined by X-ray crystallography of 1 and by CD
      analysis of a dihydrogenated derivative of 2. Turrapubesin A (1) exhibited weak
      cytotoxicity against the P-388 tumor cell line.

PMID- 16898833
TI  - A tether controlled exo-selective trans-annular Diels-Alder (TADA) reaction.
AB  - [reaction: see text] A fully substrate controlled stereoselective route to
      construct cis-hexahydronaphthalene 4 is described starting from nonracemic
      butenolide 6. The key step is an exo-selective transannular Diels-Alder reaction
      (TADA) of tetraene 5, whose intrinsic constraint allows selective formation of
      one stereodefined product. Compound 4 is a key intermediate in the synthesis of
      the novel antibiotic branimycin (1).

PMID- 16898834
TI  - Unexpected tandem ylide annulation reaction for controllable synthesis of 2H
      chromenes and 4H-chromenes.
AB  - [reaction: see text] An unexpected tetrahydrothiophene-catalyzed ylide annulation
      reaction, via tandem Michael addition/elimination/substitution, for the
      controllable synthesis of 2H-chromenes and 4H-chromenes has been developed.

PMID- 16898835
TI  - Optical mercury sensing using a benzothiazolium hemicyanine dye.
AB  - [structure: see text] The selectivity and sensitivity of a benzothiazolium
      hemicyanine dye toward mercury(II) in aqueous solutions are described. Mercury
      ions coordinate to the dye forming a 1:1 complex. This interaction induces a
      color change in the dye at micromolar concentrations of mercury. Furthermore, the
      color change and quenching of the dye emission are selective for mercury when
      compared with other ions such as lead(II), cadmium(II), zinc(II), or iron(II).

PMID- 16898836
TI  - Attempts to assemble a universal NMR database without synthesis of NMR database
      compounds.
AB  - [structure: see text] The feasibility of assembling 3JH,H profiles from NMR data
      collected on relevant, but not necessarily specific, NMR database compounds
      representing a given stereocluster was demonstrated. By this approach, the 3JH,H
      profile was created for the contiguous tetraol peracetate stereocluster. The
      reliability and applicability of the database thus assembled were demonstrated
      for known peracetates derived from two heptoses.

PMID- 16898837
TI  - Stereochemistry of sagittamide A: prediction and confirmation.
AB  - [structure: see text] The C5-C10 relative stereochemistry of sagittamide A was
      predicted, with the use of the 3JH,H profiles assembled from the spin-coupling
      constants reported in the literature. The predicted relative stereochemistry was
      then confirmed by a total synthesis of two relevant remote diastereomers. The
      absolute configuration of sagittamide A was established through a detailed 1H NMR
      analysis of the two remote diastereomers, followed by doping experiments of them
      with the authentic natural product.

PMID- 16898838
TI  - First evaluation of acyloxymethyl or acylthiomethyl groups as biolabile 2'-O
      protections of RNA.
AB  - [reaction: see text] Short oligo-U sequences containing 2'-O-acyloxymethyl or
      acylthiomethyl groups as biolabile 2'-O-protections of RNA have been synthesized.
      These modified homouridylates are deprotected upon cellular esterase activation
      to release the parent RNA. They exhibit exceptional resistance to nuclease
      degradation, and the evaluation of their pairing properties shows that the 2'
      acyloxymethyl groups do not prevent the duplex dsRNA formation. These biolabile
      2'-modifications overcome the first hurdle to turn oligoribonucleotides into
      candidates for RNA interference drugs.

PMID- 16898839
TI  - Alpha-hydroxy esters via enantioselective hydrogen-mediated C-C coupling:
      regiocontrolled reactions of silyl-substituted 1,3-diynes.
AB  - [reaction: see text] Catalytic hydrogenation of ethyl glyoxalate in the presence
      of 1,3-diynes 4a-9a using chirally modified rhodium catalysts enables formation
      of alpha-hydroxy esters 4c-9c in highly optically enriched form. Notably, for
      such trialkylsilyl-substituted 1,3-diynes, C-C coupling occurs exclusively at the
      carbon atom bearing silicon. Pi-back-bonding from low valent rhodium as described
      by the Dewar-Chatt-Duncanson model appears to direct the regiochemistry of C-C
      coupling, as corroborated by calculations of the diyne LUMO coefficients.

PMID- 16898840
TI  - Control of stereochemistry: a general synthesis of cis- or trans-beta,gamma
      disubstituted-gamma-butyrolactones following Z-crotylboration.
AB  - [reaction; see text] A general and practical procedure for the highly
      diastereoselective preparation of either the cis- or trans-beta,gamma
      disubstituted-gamma-butyrolactones by appropriate choice of Lewis or Bronsted
      acid catalysts during crotylboration or lactonization is reported. The cis
      stereochemistry of the Z-crotylboration product can be inverted with strong acids
      during lactonization. A carbocation mechanism and catalytic cycle has been
      proposed.

PMID- 16898841
TI  - Efficient synthesis of 1,3,5-trisubstituted (pyrrol-2-yl)acetic acid esters via
      dual nucleophilic reactions of sulfonamides or carbamate with 4-trimethyl-siloxy
      (5E)-hexen-2-ynoates: Lewis acid catalyzed SN1 and intramolecular Michael
      addition.
AB  - [reaction: see text] Carbamates or sulfonamides have proven to regioselectively
      attack 2-propynyl-allyl hybrid cations, generated by the action of TMSOTf on 4
      (trimethylsioxy)hex-5-en-2-ynoates, to afford conjugated 6-aminohex-4-en-2
      ynoates in which an intramolecular amino-Michael reaction took place, leading to
      pyrrole frameworks. In particular, the sulfonamides gave 1-sulfonylpyrroles in
      one pot.

PMID- 16898842
TI  - Stereocontrolled synthesis of trisubstituted cyclopropanes: expedient, atom
      economical, asymmetric syntheses of (+)-Bicifadine and DOV21947.
AB  - [reaction: see text] An expedient, atom-economical, asymmetric synthesis of 1
      aryl-3-azabicyclo[3.1.0]hexanes, including (+)-Bicifadine and DOV21947, in a
      single-stage through process without isolation of any intermediates has been
      developed. The key of this synthesis is the in-depth mechanistic understanding of
      the complicated epoxy nitrile coupling at each reaction stage. Therefore, the
      desired trisubstituted cyclopropane can be prepared in high ee and yield by
      controlling the reaction pathway through manipulating the nitrile anion
      aggregation state.

PMID- 16898844
TI  - Cost effectiveness of leukotriene modifiers in adults with asthma.
AB  - Asthma is the most common chronic disorder in industrialised nations, with over
      100 million people worldwide affected. Leukotrienes are chemical mediators
      released from mast cells, eosinophils and basophils. They cause
      bronchoconstriction, an increase in mucous secretions and activation of
      inflammatory cells. Leukotriene modifiers are a long-term controller medication
      used to treat asthma. They function by selectively competing for the leukotriene
      receptor sites, thereby blocking their action, or by inhibiting 5-lipoxygenase
      and thus preventing leukotriene formation. Both current US and Global Initiative
      for Asthma treatment guidelines have clarified the role of leukotriene modifiers
      in the management of asthma in adults and children. Leukotriene modifiers have
      two distinct roles: to replace inhaled corticosteroids in milder asthma and as an
      add-on therapy to inhaled corticosteroids in more severe asthma. While efficacy
      is certainly an important issue, economic considerations are also important in a
      disease such as asthma where there are a variety of treatment options and the
      severity of the disease varies widely. This review examined published studies to
      better understand the cost effectiveness of leukotriene modifiers in adults with
      asthma. Fifteen articles were found that analysed the cost effectiveness of
      leukotriene modifiers, with almost all performed in the US. The vast majority of
      the studies were retrospective claims analyses, but three randomised controlled
      trials incorporating economic outcomes have been reported. The majority of the
      articles found that for both monotherapy in mild persistent asthma and add-on
      therapy in moderate persistent asthma, leukotriene modifiers were less cost
      effective than inhaled corticosteroids with or without a long-acting beta2
      adrenoceptor agonist. However, these results must be viewed cautiously as in
      several studies there were methodological issues such as comparisons of unequal
      treatment groups or inappropriate use of leukotriene modifiers in stepwise
      treatment.

PMID- 16898845
TI  - Prostaglandin analogues for the treatment of glaucoma and ocular hypertension: a
      systematic review of economic evidence.
AB  - We conducted a systematic review of economic studies of prostaglandin analogues
      for the treatment of glaucoma to assess the scope of current cost-effectiveness
      evidence and its relevance to decision-makers. The literature search retrieved
      102 studies published before July 2005; after additional hand searching of
      conference proceedings, 13 full-text articles and 13 abstracts met the inclusion
      criteria. The reviewers extracted the key characteristics of each of the economic
      evaluations, and all studies received a grade in five categories to summarise the
      quality of the study: methodology, transparency, sensitivity, relevance and
      overall score. The current economic literature is predominantly focused on
      identifying the short-term direct cost of glaucoma treatment, particularly the
      precise quantification of glaucoma drug costs. Using the European and US
      treatment guidelines as a benchmark, it is evident that the current body of
      literature does not satisfy the needs of decision-makers, although certain
      studies provide some valuable information, which is a step towards reaching this
      goal. The main methodological issue in the economic models is an absence of a
      clinically relevant long-term effectiveness measure, or where this measure is
      produced, there is a lack of transparency and validation of the methods used.
      More attention needs to be given to modelling the consequences of treatment, and
      those consequences should include patient compliance, control of intraocular
      pressure and progression of visual field deficit, since these drive both the
      costs and the overall outcomes. We recognise that constructing the 'ideal'
      clinical outcome measure represents a major challenge to researchers. As such, we
      have outlined a modelling framework that could be used to produce the required
      level of economic evidence, and ongoing clinical research (such as the Early
      Manifest Glaucoma Trial) could provide the validated link between intraocular
      pressure and disease progression, which forms an essential part of such models.

PMID- 16898847
TI  - Pharmacoeconomic analyses of azathioprine, methotrexate and prospective
      pharmacogenetic testing for the management of inflammatory bowel disease.
AB  - OBJECTIVES: To compare the cost effectiveness of azathioprine (AZA), methotrexate
      (MTX) and no immunosuppression for maintaining remission of moderate to severe
      inflammatory bowel disease (IBD) in New Zealand Caucasians, and to determine
      whether prospective testing for poor metabolisers of AZA by genotype or phenotype
      is cost effective. METHODS: Pharmacoeconomic models were developed to compare
      treatment costs and effects (QALYs) in theoretical populations of 1,000 IBD
      patients over a 1-year period. Efficacy and tolerability profiles for AZA and MTX
      were taken from the literature. The costs (year 2004 values) of the drugs and
      treatment of adverse effects were estimated from New Zealand drug and service
      costs. Representations of the patients' health-related quality of life (HR-QOL)
      were obtained from clinicians via the EQ-5D health state classification system
      and valued using the New Zealand EQ-5D social tariff. The effects of genotyping
      or phenotyping a population for thiopurine methyltransferase (TPMT) status were
      compared using the prevalence of TPMT deficiency in Caucasians, the relative
      risks of neutropenia and the associated costs. RESULTS: Net cost savings (vs no
      immunosuppressant treatment) of approximately 2.5 million and 1 million New
      Zealand dollars were realised for AZA and MTX, respectively, for the theoretical
      1,000 patients, and AZA generated 877 QALYs compared with 633 for MTX. Phenotype
      and genotype testing generated net cost savings (vs no testing) of 120,000 and
      11,000 New Zealand dollars, respectively. Savings related to phenotype tests were
      greater because of the lower assay costs of phenotype testing and a greater
      likelihood of pre-empting neutropenia. CONCLUSION: Our model suggests that both
      MTX and AZA may generate significant net cost savings and benefits for patients
      with IBD in New Zealand, with AZA likely to be more cost effective than MTX.
      Prospective testing for poor metabolisers of AZA may also be cost effective, with
      phenotype testing likely to be more cost effective than genotype testing.

PMID- 16898849
TI  - Costs of inflammatory bowel disease in Germany.
AB  - INTRODUCTION: Inflammatory bowel disease (IBD) is a chronic condition that
      afflicts young adults in their economically productive years. The goal of this
      study was to determine the costs of IBD in Germany from a societal perspective,
      using cost diaries. METHODS: Members of the German Crohn's Disease and Ulcerative
      Colitis Association who had IBD were recruited by post, and those who agreed to
      participate documented their IBD-associated costs prospectively in a diary over 4
      weeks. They documented their use of healthcare facilities, medications, sick
      leave and out-of-pocket expenditures, as well as general demographic information,
      the status and history of their IBD, and long-term disability. Item costs were
      calculated according to national sources. Cost data were calculated using non
      parametric bootstrapping and presented as mean costs (year 2004) over 4 weeks.
      RESULTS: The cost diaries were returned by 483 subjects (Crohn's disease: n =
      241, ulcerative colitis: n = 242) with a mean age of 42 years and an average
      disease duration of 13 years (SD +/- 8.09). The cost diaries were regarded as
      'easy to complete' by 89% of participants. The mean 4-week costs per subject were
      1,425 Euros(95% CI 1201, 1689) for Crohn's disease and 1,015 Euros(95% CI 832,
      1258) for ulcerative colitis. Of the total costs for Crohn's disease, 64% were
      due to indirect costs such as early retirement or sick leave and 32% were due to
      direct medical costs. In contrast, of the total costs for ulcerative colitis, 41%
      were due to direct medical costs and 54% to indirect costs. CONCLUSIONS: This is
      the first comprehensive cost study for Crohn's disease and ulcerative colitis in
      Germany. The most important economic factors that influenced the cost profiles of
      both diseases were the long-term productivity losses due to an ongoing inability
      to work and the cost of medications. Results indicate significant cost
      differences between Crohn's disease and ulcerative colitis. This data provides
      initial cost estimates that can be analysed further with respect to cost
      determinants and disease-specific costs in the future.

PMID- 16898848
TI  - A multi-country health economic evaluation of highly concentrated N-3
      polyunsaturated fatty acids in secondary prevention after myocardial infarction.
AB  - BACKGROUND: Patients who survive an acute myocardial infarction (MI) are at an
      increased risk of subsequent major cardiovascular events and (often sudden)
      cardiac death. The use of highly concentrated and purified omega-3
      polyunsaturated fatty acids (n-3 PUFAs), in addition to standard secondary
      prevention after MI, results in a significant reduction in the risk of sudden
      death versus no n-3 PUFAs. This study assessed the cost effectiveness of adding n
      3 PUFAs to the current secondary prevention treatment versus standard prevention
      alone after acute MI in five countries: Australia, Belgium, Canada, Germany and
      Poland. METHODS: Based on the clinical outcomes of GISSI-P (Gruppo Italiano per
      lo Studio della Sopravvivenza nell'Infarto Miocardico - Prevenzione) [MI, stroke,
      revascularisation rate and mortality], a decision model was built in DataProtrade
      mark. The implications of adding n-3 PUFAs to standard treatment in patients aged
      59 years with a recent history of MI were analysed from the healthcare payer's
      perspective. The time horizon was 3.5 years (identical to GISSI-Prevenzione) but
      the effects on life expectancy through avoidance of cardiac events were
      calculated lifelong. Event costs were based on literature data. Life expectancy
      data for survivors of cardiac disease were taken from the Saskatchewan database
      and then adjusted by country. Results are expressed as extra cost (Euro) per life
      year gained (LYG). Annual discounting of 5% was applied to health effects and
      costs. RESULTS: Treatment with highly concentrated n-3 PUFAs yielded between
      0.261 (Poland) and 0.284 (Australia) LYG, at an additional cost of 787
      Euros(Canada) to 1,439 Euros(Belgium). The ICER varied between 2,788
      Euros(Canada) and 5,097 Euros(Belgium) per LYG. Sensitivity analyses on
      effectiveness, cost of complications and discounting proved the robustness of the
      results. A second-order Monte Carlo simulation based on the 95% confidence
      intervals obtained from GISSI-P suggests that highly concentrated n-3 PUFAs are
      cost effective in 93% of simulations in Poland and in >98% of simulations in the
      other countries, assuming the country-specific societal willingness-to-pay
      threshold. Total costs were considerably increased by including healthcare costs
      incurred during the remaining life-years, but this had no impact on the ICER
      based treatment recommendation. CONCLUSIONS: Adding highly concentrated n-3 PUFAs
      to standard treatment in the secondary prevention of MI appears to be cost
      effective versus standard treatment alone in the five countries studied.

PMID- 16898846
TI  - A comparative review of health-related quality-of-life measures for use in
      HIV/AIDS clinical trials.
AB  - With the advent of highly active antiretroviral therapy (HAART), HIV-infected
      patients are living longer and are concerned not only with a treatment's ability
      to extend their life but also with the quality of the life they are able to lead.
      Regulatory authorities are also paying closer attention to the use of health
      related quality-of-life (HR-QOL) measures in clinical trials and to the
      subsequent claims that are made based on the results. This paper reviews existing
      HR-QOL measures reported in the HIV/AIDS literature since 1990 and identifies
      those most worthy of consideration for use in future clinical trials.A
      comprehensive review following predefined selection criteria was conducted.
      Generic and HIV-targeted measures were assessed for content and practicality for
      the clinical trial setting. The generic measures were additionally reviewed for
      the ability to produce preference-based index scores and for the existence of
      normative general population data. Three generic and six HIV-targeted measures
      met these selection criteria and were then assessed more fully in terms of their
      development (HIV-targeted measures), psychometric properties and appropriateness
      for use in clinical trials.It was determined that each of the selected generic
      measures (i.e. Medical Outcomes Study [MOS] 36-Item Short Form Survey Instrument
      [SF-36], EQ-5D, Health Utilities Index [HUI]) could serve as a useful adjunct to
      an HIV-targeted measure in a trial. The Functional Assessment of HIV Infection
      (FAHI) and MOS-HIV health survey were deemed the two most appropriate HIV
      targeted measures. Each of the measures can be self-administered in < or = 10
      minutes and there was ample evidence of their excellent psychometric properties.
      However, they would not be optimal in all HIV-infected subgroups (e.g. treatment
      naive vs advanced; adolescents vs older adults) targeted for clinical trial
      interventions. Although there is no one best HR-QOL measure for use in HIV/AIDS
      clinical trials, based on our review criteria we identified three generic and two
      HIV-targeted candidate measures. However, these measures have their limitations
      and it is clear that greater consensus needs to develop regarding more effective
      and efficient approaches to HR-QOL measurement in HIV/AIDS clinical trials. Along
      with the increasingly complex HR-QOL measurement task resulting from changes in
      the HIV-infected population and shifts in the HR-QOL burden associated with HIV
      infection and its treatment over the past 25 years, it is increasingly important
      that HR-QOL outcomes become viable endpoints in HIV/AIDS clinical trials.

PMID- 16898851
TI  - National-level purchasing of expensive drugs is increasing pressure on the
      hospital drug budget.

PMID- 16898850
TI  - Cost effectiveness of adding ezetimibe to atorvastatin therapy in patients not at
      cholesterol treatment goal in Canada.
AB  - INTRODUCTION: This analysis compared the cost effectiveness of adding ezetimibe
      to atorvastatin therapy versus atorvastatin titration or adding cholestyramine (a
      resin) for patients at high risk of a coronary artery disease (CAD) event who did
      not reach target cholesterol levels on their current atorvastatin dosage. The
      primary analysis focused on 65-year-old patients with low-density lipoprotein
      cholesterol (LDL-C) levels of 3.1 or 3.6 mmol/L with a treatment goal of <2.5
      mmol/L, classified as very high risk according to the 2000 Canadian Guidelines
      for Management and Treatment of Hyperlipidaemia. METHODS: A previously developed
      Markov model was utilised to capture the cost and clinical consequences of lipid
      lowering therapy in primary and secondary prevention of CAD. Comparisons between
      treatment strategies were made using ICERs (cost per QALY) from a Canadian
      Ministry of Health perspective. The effects of lipid-lowering therapies were
      based on clinical trial data. The risks of CAD events were estimated using
      Framingham Heart Study risk equations. Treatment costs and the costs of acute and
      long-term care for CAD events were included in the analysis. Costs (Canadian
      dollar, 2002 values) and outcomes were discounted at 5% per annum. RESULTS:
      Ezetimibe added to atorvastatin therapy compared with treatment with the most
      common fixed atorvastatin daily dosage (10 mg) or with common atorvastatin
      titration strategies (up to 20 mg daily; up to 40 mg daily) resulted in cost per
      QALY estimates ranging from 25,344 to 44,332 Canadian dollars. The addition of
      ezetimibe to atorvastatin therapy was less costly and more effective than the
      addition of cholestyramine (dominant). CONCLUSION: Our analysis suggests that
      adding ezetimibe to atorvastatin for patients not achieving treatment goals with
      their current atorvastatin dose produces greater clinical benefits than treatment
      with a fixed-dose atorvastatin or atorvastatin titration at an increased overall
      cost. The cost-effectiveness ratios provide strong evidence for the adoption of
      ezetimibe within the Canadian healthcare system.

PMID- 16898853
TI  - Anesthesia and postoperative analgesia in pediatric patients undergoing cardiac
      surgery.
AB  - Pediatric cardiac anesthesiologists care for patients ranging from premature
      infants weighing <2 kg to adults requiring surgical intervention for congenital
      heart disease. Along with their cardiac pathophysiologies, many of these patients
      also have other co-existing diseases that can affect their anesthetic management.
      Recent advances in monitoring include non-invasive neuromonitors, such as near
      infrared spectroscopy and trans-cranial Doppler, which are assuming increasing
      importance in intraoperative management, particularly during cardiopulmonary
      bypass. A variety of anesthetic techniques, including regional anesthesia, can be
      used to facilitate early extubation in older infants and children with stable
      postoperative hemodynamics. In addition to regional anesthesia, other modalities
      for the management of postoperative pain include opioid infusions in critically
      ill children and the use of patient- or nurse-controlled analgesia pumps.
      Multiple pain assessment tools are available for children of varying ages and
      developmental levels to assist in providing appropriate postoperative pain
      management.

PMID- 16898854
TI  - Prevention of recurrent respiratory tract infections in children using a
      ribosomal immunotherapeutic agent: a clinical review.
AB  - Recurrent respiratory tract infections (RRTIs) in children constitute a serious
      problem worldwide. Some children experience considerable morbidity as a result of
      RRTIs and receive repeated courses of antibacterials that are not effective
      against viral infectious agents and can increase bacterial resistance.
      Furthermore, the direct and indirect costs of RRTIs to the community are
      substantial. In this article, we review the available clinical evidence relating
      to use of the bacterial immunostimulant Ribomunyl for the prevention of RRTIs in
      children. The product is composed of ribosomal fractions from four bacteria
      involved in RRTIs as well as a membrane fraction from one of these bacteria
      (Klebsiella pneumoniae). Ribomunyl stimulates production of specific humoral and
      secretory antibodies against the four bacterial strains included in the compound.
      The product also stimulates non-specific immunity. Thus, Ribomunyl stimulates
      both the innate and acquired immune systems and offers preventive efficacy
      against both bacterial and viral infections. To perform this review, we searched
      the MEDLINE database for articles on Ribomunyl and then included only those
      publications that described placebo-controlled studies, complied with Good
      Clinical Practice standards, used the product in official registered indications,
      and administered it at the recommended dosages. In this way, we were able to
      generate a comprehensive profile of use of the product and draw valid conclusions
      about its clinical role. In clinical trials of children, Ribomunyl reduced the
      number of upper or lower RRTIs, the primary outcome measures. Other favorable
      results relating to efficacy parameters that served as secondary outcome measures
      in these studies included a reduction in antibacterial treatments, shorter
      duration of recurrent episodes, reduced need for other medications such as
      expectorants, smaller number of lost school days or parent absenteeism from work,
      less fever, and reduced hearing loss. Studies focusing on particular conditions,
      such as otitis media, or those that included specific patient groups, such as
      very young children, reported similar findings. Adverse events occurred very
      rarely and were mild. Their frequency was similar to that reported in placebo
      groups, and consisted mostly of fever, otorhinolaryngologic symptoms, and
      cutaneous events. In conclusion, this review clearly demonstrated that Ribomunyl
      is effective in preventing upper and lower RRTIs in children. Ribomunyl provided
      a reduction in the number, duration, and severity of infectious episodes and,
      thereby, reduced antibacterial use and the likelihood of consequent development
      of bacterial resistance. Ribomunyl also decreased absence from work or school,
      which has important economic consequences.

PMID- 16898852
TI  - Minimizing bone abnormalities in children with renal failure.
AB  - Renal osteodystrophy (ROD), a metabolic bone disease accompanying chronic renal
      failure (CRF), is a major clinical problem in pediatric nephrology. Growing and
      rapidly remodeling skeletal systems are particularly susceptible to the metabolic
      and endocrine disturbances in CRF. The pathogenesis of ROD is complex and
      multifactorial. Hypocalcemia, phosphate retention, and low levels of 1,25
      dihydroxyvitamin D(3) related to CRF result in disturbances of bone metabolism
      and ROD. Delayed diagnosis and treatment of bone lesions might result in severe
      disability. Based on microscopic findings, renal bone disease is classified into
      two main categories: high- and low-turnover bone disease. High-turnover bone
      disease is associated with moderate and severe hyperparathyroidism. Low-turnover
      bone disease includes osteomalacia and adynamic bone disease. The treatment of
      ROD involves controlling serum calcium and phosphate levels, and preventing
      parathyroid gland hyperplasia and extraskeletal calcifications. Serum calcium and
      phosphorus levels should be kept within the normal range. The calcium-phosphorus
      product has to be <5 mmol(2)/L(2) (60 mg(2)/dL(2)). Parathyroid hormone (PTH)
      levels in children with CRF should be within the normal range, but in children
      with end-stage renal disease PTH levels should be two to three times the upper
      limit of the normal range. Drug treatment includes intestinal phosphate binding
      agents and active vitamin D metabolites. Phosphate binders should be administered
      with each meal. Calcium carbonate is the most widely used intestinal phosphate
      binder. In children with hypercalcemic episodes, sevelamer, a synthetic phosphate
      binder, should be introduced. In children with CRF, ergocalciferol (vitamin
      D(2)), colecalciferol (vitamin D(3)), and calcifediol (25-hydroxyvitamin D(3))
      should be used as vitamin D analogs. In children undergoing dialysis, active
      vitamin D metabolites alfacalcidol (1alpha-hydroxy-vitamin D(3)) and calcitriol
      (1,25 dihydroxyvitamin D(3)) are applied. In recent years, a number of new drugs
      have emerged that hold promise for a more effective treatment of bone lesions in
      CRF. This review describes the current approach to the diagnosis and treament of
      ROD.

PMID- 16898856
TI  - Ranitidine (Zantac) syrup versus Ranitidine effervescent tablets (Zantac)
      EFFERdose) in children: a single-center taste preference study.
AB  - BACKGROUND: The histamine H(2) receptor antagonist ranitidine is US FDA-approved
      for the treatment of gastroesophageal reflux disease and healing of erosive
      esophagitis in children >or=1 month of age. A low-dose strength of ranitidine is
      now available in a citrus-flavored 25 mg effervescent tablet (dissolved in 5 mL
      of water); this formulation was developed to facilitate use in infants and
      smaller children. Ranitidine syrup is available in a peppermint-flavored 15 mg/mL
      formulation. OBJECTIVE: To compare taste preferences for ranitidine (Zantac)
      syrup and ranitidine effervescent tablets dissolved in water (Zantac EFFERdose)
      in healthy children aged 4-8 years and their adult caregivers. STUDY DESIGN AND
      METHODS: A randomized, single-blind, crossover, taste test trial was conducted in
      102 children and 102 parents/legal guardians. All subjects received a single 45
      mg dose of each formulation. After tasting both preparations children were asked:
      "Now that you have tasted both medicines, which one of these medicines do you
      think tastes better?" Adults were asked four questions to assess whether they
      would administer the medication to the children. RESULTS: Seventy-one percent
      (72/102) of the children preferred the taste of the ranitidine effervescent
      tablets compared with 29% (30/102) who preferred the syrup (p < 0.001). The
      majority of adults (71%) responded that they would prefer to administer the
      effervescent formulation based on taste. Adverse events consistent with product
      labeling were mild and were reported in four children and three adults: headache
      (n = 3), drowsiness (n = 1), abdominal pain/cramps (n = 2), and bloating/gas (n =
      1). CONCLUSION: The taste of the ranitidine effervescent formulation dissolved in
      water is preferred over the ranitidine syrup. Better taste acceptance may
      facilitate ease of administration and compliance in pediatric patients.

PMID- 16898857
TI  - Light-driven water splitting for (bio-)hydrogen production: photosystem 2 as the
      central part of a bioelectrochemical device.
AB  - To establish a semiartificial device for (bio-)hydrogen production utilizing
      photosynthetic water oxidation, we report on the immobilization of a Photosystem
      2 on electrode surfaces. For this purpose, an isolated Photosystem 2 with a
      genetically introduced His tag from the cyanobacterium Thermosynechococcus
      elongatus was attached onto gold electrodes modified with thiolates bearing
      terminal Ni(II)-nitrilotriacetic acid groups. Surface enhanced infrared
      absorption spectroscopy showed the binding kinetics of Photosystem 2, whereas
      surface plasmon resonance measurements allowed the amount of protein adsorbed to
      be quantified. On the basis of these data, the surface coverage was calculated to
      be 0.29 pmol protein cm(-2), which is in agreement with the formation of a
      monomolecular film on the electrode surface. Upon illumination, the generation of
      a photocurrent was observed with current densities of up to 14 microA cm(-2) .
      This photocurrent is clearly dependent on light quality showing an action
      spectrum similar to an isolated Photosystem 2. The achieved current densities are
      equivalent to the highest reported oxygen evolution activities in solution under
      comparable conditions.

PMID- 16898859
TI  - Use of dietary supplements among women at high risk of hereditary breast and
      ovarian cancer (HBOC) tested for cancer susceptibility.
AB  - Although use of dietary supplements among women with breast cancer is high, use
      among women at high risk of hereditary breast and ovarian cancer (HBOC) is
      unknown. This study assesses the prevalence of use of dietary supplements and
      identifies characteristics associated with use among women at high risk of HBOC
      who underwent genetic testing for cancer susceptibility. Participants were 303
      women who underwent BRCA1/2 testing as part of Interdisciplinary Health Research
      International Team on Breast Cancer Susceptibility. Dietary supplements use was
      measured 12 mo post-disclosure. Potential determinants of use included personal
      cancer history, test result, psychological distress, cancer genetics knowledge,
      and health-related behaviors. Globally, 51% of participants used at least one
      dietary supplement. Calcium (26%), multivitamins (17%), vitamins D (14%), E
      (12%), and C (10%) were most frequently reported. Women > or = 50 yr were more
      likely to be using dietary supplements (P < 0.0001). Women with an inconclusive
      test result were more likely to use mineral supplements than noncarriers [odds
      ratio (OR) = 2.6; 95% confidence interval (CI) = 1.3-5.3]. Cigarette smoking was
      negatively associated with use of vitamin supplements (OR = 0.3; 95% CI = 0.1
      0.7). Use of dietary supplements among women at high risk of HBOC who underwent
      BRCA1/2 testing is as frequent as use among patients with other types of tumors
      or use among individuals from the general population.

PMID- 16898858
TI  - Ascorbate reacts with singlet oxygen to produce hydrogen peroxide.
AB  - Singlet oxygen is a highly reactive electrophilic species that reacts rapidly
      with electron-rich moieties, such as the double bonds of lipids, thiols, and
      ascorbate (AscH-). The reaction of ascorbate with singlet oxygen is rapid (k = 3
      x 10(8) M(-1) s(-1)). Here we have investigated the stoichiometry of this
      reaction. Using electrodes to make simultaneous, real-time measurements of oxygen
      and hydrogen peroxide concentrations, we have investigated the products of this
      reaction. We have demonstrated that hydrogen peroxide is a product of this
      reaction. The stoichiometry for the reactants of the reaction (1 1O2 + 1AscH--
      >1H2O2 + 1dehydroascorbic) is 1:1. The formation of H2O2 results in a very
      different oxidant that has a longer lifetime and much greater diffusion distance.
      Thus, locally produced singlet oxygen with a half-life of 1 ns to 1 micros in a
      biological setting is changed to an oxidant that has a much longer lifetime and
      thus can diffuse to distant targets to initiate biological oxidations.

PMID- 16898860
TI  - Associations of menstrual cycle length with intake of soy, fat, and dietary fiber
      in Japanese women.
AB  - A decreased risk of breast cancer has been reported among women who have longer
      menstrual cycles or anovulatory cycles. The present study examined the
      relationships between intake of fat, soy, and dietary fiber and length of
      menstrual cycle among 341 Japanese women aged 18 to 29 yr old at two colleges and
      three nursing schools. Intake of nutrients and foods including fats, dietary
      fiber, and soy products was estimated through the use of a validated semi
      quantitative food frequency questionnaire. The mean cycle length was determined
      for each women based on a prospective record of menstruation. Polyunsaturated fat
      intake was significantly inversely associated with cycle length; the means of
      cycle length were 33.2 and 31.0 days for the lowest and the highest quintiles of
      intake, respectively, after controlling for covariates (trend = 0.03). The odds
      ratio of a long cycle (> 35 days) for the highest vs. lowest quintile of dietary
      fiber intake was 2.12 (95% confidence interval 1.00-4.47), although the trend was
      not statistically significant. The data suggest that polyunsaturated fat and
      dietary fiber intake are associated with the parameters of menstrual cycle
      length, but further studies are required to better characterize these
      associations.

PMID- 16898861
TI  - Dietary patterns and risk of squamous-cell carcinoma and adenocarcinoma of the
      esophagus and adenocarcinoma of the gastric cardia: a population-based case
      control study in Sweden.
AB  - We conducted a large population-based case-control study in Sweden to examine the
      association of dietary patterns and the development of cancers from the esophagus
      or gastroesophageal junction. In total 185 patients with esophageal
      adenocarcinoma, 165 with esophageal squamous-cell carcinoma, 258 with gastric
      cardia adenocarcinoma, and 815 randomly selected population controls underwent
      face-to-face interviews. Exploratory factor analysis was used to identify
      possible dietary patterns. Multivariate logistic regression with adjustments for
      age, sex, years of education, body mass index, physical activity, symptomatic
      gastroesophageal reflux, smoking, and total energy intake was used to estimate
      odds ratios (ORs) and their 95% confidence intervals (CIs). We identified three
      major dietary patterns in this population, for example, "healthy diet" (high in
      vegetables, tomato, fruits, fish, and poultry), "Western diet" (high in processed
      meat, red meat, sweets, high-fat dairy, and high-fat gravy), and "alcohol
      drinker" (high in intakes of beer, liquor, and French fries). We found that a
      healthy diet tended to moderately decrease the risk of all three cancers under
      study, although none of the associations was statistically significant. A high
      score of Western diet was associated with increased risks of gastric cardia
      adenocarcinoma (high 3rd tertile vs. low 1st quartile, OR = 1.8, 95% CI = 1.1
      2.9, P for trend = 0.04) and esophageal adenocarcinoma (high 3rd tertile vs. low
      1st tertile, OR = 1.6, 95% CI = 0.9-3.1, P for trend = 0.13), whereas a dietary
      pattern characterized by high beer and liquor intake (alcohol drinker)
      significantly increased the risk of squamous-cell carcinoma of the esophagus (3rd
      tertile vs. low 1st tertile, OR = 3.5, 95% CI = 1.9-6.3, P for trend < 0.0001).
      Our study confirms the important role of diet in the carcinogenesis of esophageal
      and cardia cancer.

PMID- 16898862
TI  - A pilot study on the effects of almond consumption on DNA damage and oxidative
      stress in smokers.
AB  - The effects of almond consumption on DNA damage and oxidative stress among
      cigarette smokers were studied. Thirty healthy adult male regular smokers were
      randomly divided into three groups, 10 subjects per group. Group A (control
      group) did not receive any almonds. Subjects in Groups B and C received 3 oz and
      6 oz (84 g and 168 g) of almonds each day respectively for 4 wk. Two known
      biomarkers for DNA damage, urinary 8-hydroxy-2'-deoxyguanosine (8-OH-dG) and
      single strand DNA breaks of peripheral blood lymphocytes, were measured by enzyme
      linked immunosorbent assay and comet assay, respectively. In addition, plasma
      malondialdehyde (MDA) level, superoxide dismutase (SOD), and glutathione
      peroxidase (GSH-Px) activities were measured as biomarkers for oxidative stress.
      The results showed lower levels of urinary 8-OH-dG and single strand DNA breaks
      in the two almond-treated groups as compared with the control group. Furthermore,
      MDA levels in the almond-treated groups were lower than the controls. However, no
      significant effects of almonds on SOD and GSH-Px activities were found. In
      conclusion, results from this pilot study indicate that almond consumption has
      preventive effects on oxidative stress and DNA damage caused by smoking. A
      larger, randomized, placebo-controlled clinical trial on almonds will be
      initiated in the near future.

PMID- 16898855
TI  - Diuretics in pediatrics : current knowledge and future prospects.
AB  - This review summarizes current knowledge on the pharmacology, pharmacokinetics,
      pharmacodynamics, and clinical application of the most commonly used diuretics in
      children. Diuretics are frequently prescribed drugs in children. Their main
      indication is to reduce fluid overload in acute and chronic disease states such
      as congestive heart failure and renal failure. As with most drugs used in
      children, optimal dosing schedules are largely unknown and empirical. This is
      undesirable as it can potentially result in either under- or over-treatment with
      the possibility of unwanted effects. The pharmacokinetics of diuretics vary in
      the different pediatric age groups as well as in different disease states. To
      exert their action, all diuretics, except spironolactone, have to reach the
      tubular lumen by glomerular filtration and/or proximal tubular secretion.
      Therefore, renal maturation and function influence drug delivery and consequently
      pharmacodynamics. Currently advised doses for diuretics are largely based on
      adult pharmacokinetic and pharmacodynamic studies. Therefore, additional
      pharmacokinetic and pharmacodynamic studies for the different pediatric age
      groups are necessary to develop dosing regimens based on pharmacokinetic and
      pharmacodynamic models for all routes of administration.

PMID- 16898863
TI  - Phytoestrogen content of foods consumed in Canada, including isoflavones,
      lignans, and coumestan.
AB  - Phytoestrogens may play a role in hormone-related diseases such as cancer, but
      epidemiological and clinical data are conflicting in part due to inadequate
      databases used in intake estimation. A database of nine phytoestrogens in foods
      relevant to Western diets was developed to more accurately estimate intakes.
      Foods (N = 121) available in Ontario, Canada were prepared as commonly consumed
      and analyzed for isoflavones (genistein, daidzein, glycitein, formononetin),
      lignans (secoisolariciresinol, matairesinol, pinoresinol, lariciresinol), and
      coumestan (coumestrol) using gas chromatography-mass spectrometry methods. Data
      were presented on an as is (wet) basis per 100 g and per serving. Food groups
      with decreasing levels of total phytoestrogens per 100 g are nuts and oilseeds,
      soy products, cereals and breads, legumes, meat products, and other processed
      foods that may contain soy, vegetables, fruits, alcoholic, and nonalcoholic
      beverages. Soy products contain the highest amounts of isoflavone, followed by
      legumes, meat products and other processed foods, cereals and breads, nuts and
      oilseeds, vegetables, alcoholic beverages, fruits, and nonalcoholic beverages.
      Decreasing amounts of lignans are found in nuts and oilseeds, cereals and breads,
      legumes, fruits, vegetables, soy products, processed foods, alcoholic, and
      nonalcoholic beverages. The richest sources of specific phytoestrogens, including
      coumestrol, were identified. The database will improve phytoestrogen intake
      estimation in future epidemiological and clinical studies particularly in Western
      populations.

PMID- 16898864
TI  - Methionine restriction inhibits colon carcinogenesis.
AB  - Previously, we demonstrated that life-long methionine restriction (MR) in rats
      increases life span and inhibits aging-related disease processes. The present
      study examines the effects of MR on the formation of preneoplastic aberrant crypt
      foci (ACF) in the colon of azoxymethane (AOM)-treated rats. Six-week-old male
      F344 rats were placed on essential amino acid-defined diets containing either
      0.86% Met (control diet) or 0.17% Met (MR diet) and 1 wk later were given AOM (15
      mg/kg/wk, s.c.) for 2 consecutive wk. Ten weeks after the final AOM treatment,
      ACF formation was markedly reduced in rats fed the MR diet with ACF containing >
      or = 4 crypts/focus being reduced by over 80% compared to controls (P < 0.001). A
      similar 83% reduction in ACF containing > or = 4 crypts/focus was observed in
      rats fed the MR diet only during the post-initiation period (after the final dose
      of AOM; P < 0.001). Five weeks after AOM administration, a 12% reduction in
      colonic cell proliferation was observed in MR rats compared to controls (P <
      0.05). These results show that MR inhibits colonic tumor development in the rat,
      an effect that occurs primarily during post-initiation phases of carcinogenesis
      and may be due, in part, to an inhibition of colonic cell proliferation.

PMID- 16898865
TI  - Selenised casein protects against AOM-induced colon tumors in Sprague Dawley
      rats.
AB  - Selenium (Se) has been shown to be protective against cancers in animal models at
      concentrations exceeding those considered essential for normal nutritional
      requirements. Organic forms of Se provided as dairy proteins were obtained from
      cows fed diets supplemented with yeast Se. The casein extracted from milk was
      found to contain approximately half the Se of the Se-enriched milk. This casein
      was included in a semi-purified AIN rodent diet so as to provide 1 ppm Se and 25%
      protein and was compared with AIN diets containing no added Se (control, 0.05
      ppm), 1 ppm and 4 ppm Se as selenised yeast (Sel-Plex) Their influence on colon
      tumor expression was examined in rats induced with azoxymethane, the diets being
      introduced post-induction. The selenised casein diet at this concentration was
      effective in reducing colon tumor incidence (by 29%) and burden (decreased 52%, P
      < 0.05) relative to the control in rats 26 wk post-induction. Selenised yeast,
      when added at similar (1 ppm) and increased Se concentration (4 ppm), did not
      influence significantly colon tumor expression. However, in a second study, with
      Se yeast providing Se at 1 ppm, 4 ppm, and 8 ppm throughout the experiment, a
      significant reduction in tumors was observed with 8 ppm Se (colon tumor incidence
      was 15% lower and colon tumor burden was 35% lower, P < 0.05). However this was
      associated with a significantly lower body weight in the rats (down 10.5%, P <
      0.05) indicating a possible disturbance with normal energy intake or metabolism.
      The form in which Se is presented in the diet may influence significantly its
      bioavailability and/or anticancer potential at given concentrations within a safe
      range. The efficacy of selenised casein and indeed other potential dietary
      sources deserve further investigation with regard to their ability to prevent
      colon tumors at concentrations considered safe in the diet.

PMID- 16898866
TI  - Chemopreventive effects of dietary flaxseed on colon tumor development.
AB  - Fatty acid composition of dietary fat plays a vital role in colon tumor
      development in animal models. Fats containing omega-6 fatty acids (e.g., corn
      oil) enhanced and omega-3 fatty acids (e.g., flaxseed oil) reduced chemically
      induced colon tumor development in rats. Lignans have also been shown to prevent
      colon tumor development in experimental animals. The objective of this
      investigation is to study the effects of dietary flaxseed meal, a source of both
      omega-3 fatty acid and lignans, on colon tumor development and compare them with
      the effects of dietary corn meal. Male Fischer rats, two groups of 24 each, were
      assigned to the AIN-93M diet supplemented with either 15% corn meal or 15%
      flaxseed meal, respectively. Carcinogenesis was initiated with subcutaneous
      injections of azoxymethane (15 mg/kg) once a week for 3 consecutive wk. After 35
      wk of initiation, rats were anesthetized with ether. Blood was collected by
      cardiac puncture, and rats were sacrificed. The gastrointestinal tract was
      isolated. The site, size, and number of tumors were recorded. The fatty acid
      analysis of the collected serum and colon samples was performed. Expression of
      cyclooxygenase (COX)-1 and COX-2 was performed by Western blot method. Lignan
      levels in serum and colon samples were assayed. Colon tumor incidence,
      multiplicity, and size were found to be 82.6% and 29.4%; 1.3 and 0.3; and 44.4
      and 5.3 mm(2) in corn and flaxseed meal groups, respectively. Colon and serum
      samples of the corn meal group showed higher levels of omega-6 fatty acid levels
      whereas the flaxseed meal group exhibited higher levels of omega-3 fatty acids.
      COX-1 and COX-2 expression in the flaxseed group was significantly lower (P <
      0.05) as compared to the corn group. Dietary flaxseed meal containing high levels
      of omega-3 fatty acids and lignans is effective in preventing colon tumor
      development when compared with dietary corn meal possibly by increasing omega-3
      fatty acid levels and decreasing COX-1 and COX-2 levels.

PMID- 16898867
TI  - Evaluation of isothiocyanates as potent inducers of carcinogen-detoxifying
      enzymes in the urinary bladder: critical nature of in vivo bioassay.
AB  - Deficiency of carcinogen-detoxifying phase 2 enzymes, such as glutathione S
      transferase (GST) and NAD(P)H:quinone oxidoreductase 1 (NQO1), increases bladder
      cancer risk in humans. We report that several isothiocyanates (ITCs) that have
      not been previously examined, 1-methylbutyl ITC in particular, potently and
      preferentially induce both GST and NQO1 in the rat bladder. Comparison of 25 ITCs
      that are closely related in chemical structures showed that a 3-5-carbon
      aliphatic side chain with a methyl group attached to the alpha carbon was crucial
      for maximal inducer activity in the bladder. Surprisingly, cell-based bioassays
      failed to predict the phase 2 enzyme-inducing activity of the ITCs in the
      bladder. Furthermore, although ITCs are principally metabolized in vivo to
      dithiocarbamates (DTCs), which are believed to serve as the carriers of ITCs and
      are rapidly eliminated and concentrated in the urine, the total urinary levels of
      ITC plus DTC did not correlate with the degree of GST and NQO1 induction by the
      ITCs in the bladder of rats. Thus, several underappreciated ITCs are exceedingly
      potent inducers of GST and NQO1 in the rat bladder but were predicted neither by
      in vitro bioassays of phase 2 enzyme induction nor by their appearance or
      concentration in urine in vivo.

PMID- 16898868
TI  - Equol: a comparison of the effects of the racemic compound with that of the
      purified S-enantiomer on the growth, invasion, and DNA integrity of breast and
      prostate cells in vitro.
AB  - It has been postulated that the R- and S-equol enantiomers have different
      biological properties given their different binding affinities for the estrogen
      receptor. S-(-)equol is produced via the bacterial conversion of the soy
      isoflavone daidzein in the gut. We have compared the biological effects of
      purified S-equol to that of racemic (R and S) equol on breast and prostate cancer
      cells of varying receptor status in vitro. Both racemic and S-equol inhibited the
      growth of the breast cancer cell line MDA-MB-231 (> or = 10 microM) and the
      prostate cancer cell lines LNCaP (> or = 5 microM) and LAPC-4 (> or = 2.5
      microM). The compounds also showed equipotent effects in inhibiting the invasion
      of MDA-MB-231 and PC-3 cancer cells through matrigel. S-equol (1, 10, 30 microM)
      was unable to prevent DNA damage in MCF-7 or MCF-10A breast cells following
      exposure to 2-hydroxy-4-nonenal, menadione, or benzo(a)pyrene-7,8-dihydrodiol
      9,10-epoxide. In contrast, racemic equol (10, 30 microM) prevented DNA damage in
      MCF-10A cells following exposure to 2-hydroxy-4-nonenal or menadione. These
      findings suggest that racemic equol has strong antigenotoxic activity in contrast
      to the purified S-equol enantiomer implicating the R-, rather than the S
      enantiomer as being responsible for the antioxidant effects of equol, a finding
      that may have implications for the in vivo chemoprotective properties of equol.

PMID- 16898869
TI  - Effect of dietary apigenin on colonic ornithine decarboxylase activity, aberrant
      crypt foci formation, and tumorigenesis in different experimental models.
AB  - The efficacy of dietary apigenin, a dietary flavonoid, in colon cancer prevention
      was investigated by evaluating the inhibition of the ornithine decarboxylase
      (ODC) activity and the formation of aberrant crypt foci (ACF) and by studying the
      ability of apigenin to block colon carcinogenesis in two mouse models. First, the
      activity of ODC was measured in colon cancer cells (Caco-2) and in the colon
      epithelium of CF-1 mice. Apigenin at 10 and 30 muM significantly inhibited the
      ODC activity of Caco-2 cells by 26% and 57%, respectively. Colonic ODC activity
      in CF-1 mice was reduced with 0.1% dietary apigenin by 42% compared with the
      control, but this difference was not statistically significant. Second, ACF
      formation was evaluated in azoxymethane (AOM)-induced CF-1 mice. Female CF-1 mice
      at 6 wk of age were i.p. injected with 5 mg/kg body weight (BW) AOM once to
      induce ACF. ACF formation in CF-1 mice was reduced by 50% (P < 0.05) with 0.1%
      dietary apigenin fed for 6 wk when compared with the control. Dietary apigenin
      inhibited ACF only in the distal region of the CF-1 mouse colon. Finally,
      tumorigenesis studies were conducted using two different mouse models: AOM
      induced CF-1 mice and Min mice with mutant adenomatous polyposis coli (APC) gene.
      Female CF-1 mice at 6 wk of age were i.p. injected with 10 mg/kg BW AOM weekly
      for 6 (AOM Study I) or 4 (AOM Study II) wk to induce tumors. CF-1 mice were fed
      diets containing 0.025% or 0.1% apigenin for 23-25 wk. Female Min mice were fed
      diets for 10 wk beginning at 5 wk of age. In two AOM-treated mouse colon tumor
      studies 0.025% and 0.1% dietary apigenin modestly reduced tumors in the group fed
      0.025% apigenin (25% incidence in comparison with 65% in the controls) in a non
      dose response manner. Apigenin failed to inhibit adenoma formation in the Min
      mouse study. These results suggest that dietary apigenin showed promise in cancer
      prevention by reducing the ODC activity and ACF formation, however, clear
      evidence of cancer prevention was not obtained in mouse tumor studies. Further
      investigation of the potential chemopreventive effect of apigenin in
      carcinogenesis is warranted.

PMID- 16898870
TI  - beta-carotene-induced changes in RARbeta isoform mRNA expression patterns do not
      influence lung adenoma multiplicity in the NNK-initiated A/J mouse model.
AB  - A number of epidemiological studies have reported associations of beta-carotene
      plasma levels or intake with decreased lung cancer risk. However, intervention
      studies in smokers reported increased lung tumor rates after high long-term beta
      carotene supplementation. For insight into these conflicting results, we studied
      the influence of beta-carotene on tobacco smoke carcinogen-induced lung cancer
      development in the A/J-mouse using 4-(N-Methyl-N-nitro samino)-1-(3-pyridyl)-1
      butanone (NNK) as the initiator and lung adenoma multiplicity as the functional
      endpoint. Gene regulation of the putative tumor suppressor RARbeta in mouse lung
      was analyzed by quantitative real-time reverse transcriptase-polymerase chain
      reaction (RT-PCR) for its relevance in predicting the endpoint of lung cancer.
      A/J-mice achieved plasma beta-carotene levels of up to 3 micromol/L within 4 wk
      and up to 6 micromol/L after 6 mo of supplementation on a diet modified to
      enhance beta-carotene absorption. Despite high lung beta-carotene concentrations
      of up to 6 micromol/kg, tumor multiplicity was not significantly affected by the
      beta-carotene treatment, either in carcinogen-initiated or non-initiated mice,
      and was unrelated to beta-carotene dose and the time point of treatment during
      cancer formation. Tumor multiplicity did not correlate with beta-carotene plasma
      levels in NNK-treated animals. All RARbeta isoforms were significantly suppressed
      in the lungs of NNK- and NNK plus high dose beta-carotene-treated animals.
      However, the number of tumors per mouse did not correlate with the RARbeta
      isoform expression levels. beta-carotene alone after 3 mo of supplementation
      mildly but significantly increased levels of RARbeta1, beta2, and beta4. This
      increase persisted for 6 mo for RARbeta2 and beta4. In summary, we found no
      effect of beta-carotene on tumor formation in the NNK-initiated A/J-mouse lung
      cancer model with respect to dose or time point of treatment. beta-Carotene
      induced changes in RARbeta isoform gene expression levels were not predictive for
      the number of lung tumors but were indicative of intact beta-carotene metabolism
      and persistent sensitivity to retinoic acid in the mice. Down-regulation of
      RARbeta in NNK-induced adenoma-bearing lungs was similar to that observed in
      human lung cancer and further confirms the A/J-mouse as a valuable model for lung
      carcinogenesis.

PMID- 16898871
TI  - Modulation of p53 and c-myc in DMBA-induced mammary tumors by oral glutamine.
AB  - Previous studies established that oral glutamine (GLN) reduced tumor development
      in implantable and 7,12-dimethylbenz(a)anthracene (DMBA)-induced breast cancer
      models. This finding was associated with a decrease in tumor glutathione (GSH)
      levels, while maintaining normal gut, blood, and breast GSH. Alterations in GSH
      levels contribute to the control of apoptotic and cell cycle-regulating
      signaling. The aim of this study was to examine the role of dietary GLN on
      activation of p53 and c-myc, which play critical roles in cancer development and
      sensitivity to radiation and chemotherapy. Mammary gland carcinomas were induced
      in rats by DMBA. The rats were gavaged daily with GLN or water (controls),
      starting 1 wk prior DMBA-application and throughout the duration of the
      experiment (11 wk after DMBA). Tumor DNA was examined for mutations in p53 exons
      5 and 6. Protein and mRNA levels of p53, p21(WAF1/CIP1), PTEN, IGF-IR, mdm2, and
      c-myc in tumors of GLN-supplemented rats were compared with those of the control
      rats (received water). The sequencing of p53 showed that it was wild type.
      Increased phosphorylation of p53, as well as higher mRNA and protein levels of
      p21(WAF1/CIP1), PTEN, and mdm2, and lower levels of IGF-IR were detected in
      tumors of GLN-supplemented rats vs. controls. Both phosphorylated c-myc and c-myc
      mRNA levels were reduced by GLN. The up-regulation of tumor p53 signaling and
      down-regulation of c-myc, in addition to previously established inhibition of Akt
      signaling in DMBA-breast cancer model, suggest that dietary GLN could be a useful
      approach for increasing the effectiveness of cancer treatment.

PMID- 16898872
TI  - Intrinsic cisplatin resistance in lung and ovarian cancer cells propagating in
      medium acutely depleted of folate.
AB  - Many tumors develop intrinsic and/or acquired resistance to cisplatin. The
      purpose of the present study was to examine the influence of acute extracellular
      folate depletion prior to cisplatin treatment on the development of intrinsic
      cisplatin resistance. Lung and ovarian cancer cells were propagated in medium
      acutely depleted of folate and subsequently treated with cisplatin. The IC50
      level for cisplatin, cell viability, cell proliferation, and global DNA
      methylation were determined. Gene expression profiling was performed using the
      Atlas Cancer 1.2 Array. Acute extracellular folate depletion resulted in the
      development of intrinsic cisplatin resistance. Cells propagating in medium
      acutely depleted of folate had a survival advantage compared to control cells
      when exposed to cisplatin, and thymidine supplementation did not reverse the
      intrinsic cisplatin resistance. cDNA microarray analysis revealed some novel
      genes associated with the development of intrinsic cisplatin resistance. Our
      report is the first to demonstrate that acute extracellular folate depletion
      results in intrinsic cisplatin resistance. If these results are confirmed by in
      vivo human studies, it would suggest that the folate status of the recipient of
      cisplatin might have an impact on response to that chemotherapeutic agent.

PMID- 16898873
TI  - Structural studies on the RNA-recognition motif of NELF E, a cellular negative
      transcription elongation factor involved in the regulation of HIV transcription.
AB  - The elongation of transcription of HIV RNA at the TAR (transactivation-response
      element) is highly regulated by positive and negative factors. The cellular
      negative transcription elongation factor NELF (negative elongation factor) was
      suggested to be involved in transcriptional regulation of HIV-1 (HIV type 1) by
      binding to the stem of the viral TAR RNA which is synthesized by cellular RNA
      polymerase II at the viral long terminal repeat. NELF is a heterotetrameric
      protein consisting of NELF A, B, C or the splice variant D, and E. In the present
      study, we determined the solution structure of the RRM (RNA-recognition motif) of
      the RNA-binding subunit NELF E and studied its interaction with the viral TAR
      RNA. Our results show that the separately expressed recombinant NELF E RRM has
      alpha-helical and beta-strand elements adopting a betaalphabetabetaalphabeta fold
      and is able to bind to TAR RNA. Fluorescence equilibrium titrations with
      fluorescently labelled double- and single-stranded oligoribonucleotides
      representing the TAR RNA stem imply that NELF E RRM binds to the single-stranded
      TAR RNAs with K(d) values in the low-micromolar range.

PMID- 16898875
TI  - Identifying and managing childhood obesity: we can do it better.

PMID- 16898876
TI  - Contemporary Australian outcomes in childhood and adolescent type 1 diabetes: 10
      years post the Diabetes Control and Complications Trial.
AB  - The reporting of the results of the Diabetes Control and Complications Trial in
      1993 has led to a major reappraisal of management practices and outcomes in type
      1 diabetes in children and adolescents. A considerable body of outcome data has
      been generated from Australia in this post-Diabetes Control and Complications
      Trial era relating to incidence, metabolic control, growth, hypoglycaemia,
      microvascular and macrovascular complications, cognition, behaviour and quality
      of life. These data are important in planning future management strategies and
      resource allocation and as a basis for future research.

PMID- 16898877
TI  - Recognition and management of childhood overweight and obesity by clinicians.
AB  - AIM: (i) To determine the ability of general practitioners (GPs) and
      paediatricians to correctly identify children as overweight or obese by visual
      cues alone; (ii) to describe the current management practices of overweight and
      obese children by these practitioners; and (iii) to compare these with National
      Health and Medical Research Council (NHMRC) Clinical Practice Guidelines.
      METHODS: Forty-four GPs and 29 paediatricians participated in the study.
      Respondents completed a questionnaire based on a series of body images, rating
      the size of the child as acceptable weight, overweight or obese and indicating
      the likelihood of carrying out a series of management options. RESULTS: There was
      considerable variation in ability to rate images correctly with the total number
      of correct responses being 72% and 68%, respectively, for GPs and paediatricians.
      There were statistically significant differences in management between GPs and
      paediatricians in terms of conducting appropriate anthropometry and screening for
      co-morbidities, with paediatricians performing closer to the NHMRC Clinical
      Practice Guidelines. CONCLUSION: GPs and paediatricians have the opportunity to
      screen children for overweight and obesity during their everyday practice.
      Accurate determination of weight status cannot be performed by visualisation
      alone and all children should have height and weight measured and correctly
      interpreted. Some areas of current GP and paediatrician management of overweight
      and obese children fall short of the NHMRC clinical guidelines and areas for
      improvement are highlighted in this paper.

PMID- 16898878
TI  - Exercise myocardial perfusion stress testing in children with Kawasaki disease.
AB  - AIM: Kawasaki disease is the commonest cause of acquired coronary artery disease
      in children. Although echocardiography and treadmill stress testing have been the
      traditional methods of assessing coronary artery abnormalities and detecting
      myocardial ischaemia, respectively, these are inadequate for assessing perfusion
      and performance. We studied the safety and utility of exercise myocardial
      perfusion stress testing in children with previous Kawasaki disease. METHODS:
      Eleven subjects (median age 12 years; seven male and four female adolescents)
      with a history of childhood Kawasaki disease underwent 99mTechnetium-Tetrofosmin
      myocardial perfusion scan using a modified protocol. All had New York Heart
      Association effort tolerance class 1 and were asymptomatic at time of testing.
      Eight of 11 subjects had been treated with intravenous immunoglobulin during the
      acute phase. Six of 11 subjects had transient coronary artery dilatation. One
      subject with persistently dilated coronary arteries suffered an acute myocardial
      infarction 6 months after onset of Kawasaki disease but recovered well. Results
      were compared with clinical and echocardiographic findings. RESULTS: All subjects
      were able to complete the exercise test. There were no side effects associated
      with radioisotope injection. Ten of 11 patients, including the one who suffered a
      myocardial infarction had normal tests. The single subject with an abnormal scan
      showed a minimal (2%) fixed defect in the left ventricular wall. CONCLUSION:
      Exercise myocardial perfusion stress is a safe and useful method for the
      assessment of myocardial perfusion in co-operative children with a history of
      Kawasaki disease and is a useful addition to conventional methods for coronary
      risk stratification in such patients.

PMID- 16898880
TI  - Nodding off or switching off? The use of popular media as a sleep aid in
      secondary-school children.
AB  - AIM: To describe the use of media as a sleep aid in adolescents and relate this
      to their sleep routines and feelings of tiredness. METHODS: A questionnaire about
      using media as a sleep aid, media presence in bedrooms, time to bed and time out
      of bed on average weekdays and average weekend days, and questions regarding
      level of tiredness in the morning, at school, after a day at school and after the
      weekend was completed by 2546 seventh and 10th grade children in a random sample
      of 15 schools. RESULTS: Of the adolescents, 36.7% reported watching television to
      help them fall asleep. In total, 28.2% of the boys and 14.7% of the girls used
      computer games as a sleep aid. Music was used to fall asleep by 60.2% of the
      adolescents in this sample. About half of the adolescents read books to fall
      asleep. Except for reading books, using media as a sleep aid is negatively
      related to respondents' time to bed on weekdays, their number of hours of sleep
      per week and their self-reported level of tiredness. CONCLUSION: Using media as a
      sleep aid appears to be common practice among adolescents. Those who reported
      using music, television, and computer games more often as a sleeping aid slept
      fewer hours and were significantly more tired.

PMID- 16898879
TI  - Features of Kawasaki disease at the extremes of age.
AB  - AIM: The diagnosis of Kawasaki disease (KD) in those outside the typical age
      range (6 months-4 years) is often delayed, potentially worsening prognosis. The
      features of KD in children<or=6 months and >or=5 years were compared with those
      presenting within the more typical age distribution. METHODS: Korean children
      with complete diagnostic criteria for KD were grouped according to their age at
      presentation: Group A (<or=6 months), Group B (7 months-4 years) and Group C
      (>or=5 years). The clinical features, laboratory findings and outcome in each
      group were compared. RESULTS: Of 136 children presenting to a single centre
      between 1999 and 2003, 10 children were in Group A, 114 in Group B and 12 in
      Group C. The mean total fever duration was 8 days in Group C and 6.2 days in
      Group A (P=0.03). All children in Group C had cervical lymphadenopathy, compared
      with 50% of Group A and 64% of Group B (P=0.01). Coronary artery lesions were
      commoner in older children (Group C, 42%) compared with Group B (17%, P=0.05).
      All children had an equivalent leukocytosis, but Group C had significantly higher
      neutrophil counts (P=0.001). Group A had significantly lower mean haemoglobin
      (P=0.003) and total protein (P=0.002) at presentation and a more marked
      thrombocytosis 1 week after intravenous immunoglobulin therapy (P<0.05).
      CONCLUSION: The clinical and laboratory phenotype of KD varies with age. Older
      children may have a more marked inflammatory response and worse outcome. Younger
      children who are treated appropriately may not have a chance to higher risk of
      coronary artery lesions.

PMID- 16898874
TI  - Regulatory circuits controlling white versus brown adipocyte differentiation.
AB  - Adipose tissue is a major endocrine organ that exerts a profound influence on
      whole-body homoeostasis. Two types of adipose tissue exist in mammals: WAT (white
      adipose tissue) and BAT (brown adipose tissue). WAT stores energy and is the
      largest energy reserve in mammals, whereas BAT, expressing UCP1 (uncoupling
      protein 1), can dissipate energy through adaptive thermogenesis. In rodents,
      ample evidence supports BAT as an organ counteracting obesity, whereas less is
      known about the presence and significance of BAT in humans. Despite the different
      functions of white and brown adipocytes, knowledge of factors differentially
      influencing the formation of white and brown fat cells is sparse. Here we
      summarize recent progress in the molecular understanding of white versus brown
      adipocyte differentiation, including novel insights into transcriptional and
      signal transduction pathways. Since expression of UCP1 is the hallmark of BAT and
      a key factor determining energy expenditure, we also review conditions associated
      with enhanced energy expenditure and UCP1 expression in WAT that may provide
      information on processes involved in brown adipocyte differentiation.

PMID- 16898881
TI  - Sexually transmitted infections in alleged sexual abuse of children and
      adolescents.
AB  - AIM: To describe the prevalence of sexually transmitted infections (STI) in
      children and young people aged 0-17 years seen for suspected sexual abuse in
      Auckland, New Zealand. METHODS: Retrospective review of consecutive medical
      records over a 7-year period from December 1991 to December 1998. RESULTS: A
      total of 2162 children and young people had a genital examination related to
      concerns about possible sexual abuse, of whom 1909 (88.3%) had some form of
      screening test for STI. Sixty children and young people (2.8%) had STI, diagnosed
      either by examination, laboratory investigation, or both. The rate was 5.6%
      (43/770) in those aged 10 years or older and 1.2% (17/1392) in those aged under
      10 years. CONCLUSION: The prevalence of STI in children and young people referred
      for suspected sexual abuse is low but significant. Chlamydia and pelvic
      inflammatory disease were the most common infections. No STI was found in an
      asymptomatic pre-pubertal child.

PMID- 16898882
TI  - Knowledge of sudden infant death syndrome prevention strategies in a
      multicultural, disadvantaged community.
AB  - AIM: This study assessed levels of maternal knowledge of sudden infant death
      syndrome prevention strategies in a socio-economically disadvantaged, culturally
      diverse population. METHODS: Pregnant women (n=233) were asked to name three
      things they could do to reduce the risk of cot death. Answers were marked in
      accordance with the US National Institute of Child Health and Development guide
      lines. RESULTS: Of women 51.5% could correctly name two or more strategies that
      could reduce the risk of sudden infant death syndrome. There was significant
      difference by the woman's country of birth: 68.2% of Australian-born women were
      able to correctly identify two or more strategies, compared with only 37.3% of
      those born overseas (P<0.001). Most of the small number of Indigenous women
      included in the study were able to correctly identify two or more strategies.
      Year of arrival in Australia, number of previous children, age and level of
      education were not significantly related to women's knowledge. CONCLUSION:
      Knowledge of sudden infant death syndrome prevention strategies was poorer in
      overseas-born women. Practitioners working with disadvantaged, overseas-born
      women should give consideration to women's knowledge of sudden infant death
      syndrome prevention if current low rates of sudden infant death syndrome deaths
      are to be maintained.

PMID- 16898883
TI  - Sudden infant death syndrome and unascertainable deaths: trends and disparities
      among Aboriginal and non-Aboriginal infants born in Western Australia from 1980
      to 2001 inclusive.
AB  - AIM: To analyse patterns and trends in mortality from unknown causes (sudden
      infant death syndrome and unascertainable deaths) for all Aboriginal and non
      Aboriginal infants born in Western Australia, 1980-2001. METHODS: Using total
      population linked data, we reviewed all post-mortem reports, including death
      scene investigations and final causes of death as ascertained by the coroner.
      Neonatal, post-neonatal and infant mortality rates attributed to unknown causes
      were calculated and the latter were analysed according to maternal age,
      geographical location, gestational age, sex and birthweight. Relative risks (95%
      confidence interval) for Aboriginal infants (compared with non-Aboriginal) were
      calculated. RESULTS: The proportion of deaths considered to be of unascertainable
      cause has significantly increased in recent years. In contrast to the non
      Aboriginal population, there has been no significant decrease in deaths in the
      Aboriginal population and the overall relative risk for Aboriginal infants for
      the most recent years studied was 7.9 (95% confidence interval 5.1-12.2). The
      relative risk was significantly increased for most categories analysed.
      CONCLUSION: Reviewing post-mortem reports enabled identification of changes in
      the classification of deaths due to unknown causes. This provided a more accurate
      picture of the patterns and long-term trends of such deaths so that programmes
      can be developed to specifically target those groups most at risk. Adequately
      funded and evaluated education campaigns aimed at reducing the risk of sudden
      infant death syndrome among Aboriginal infants are required, as well as
      sustaining the current efforts that have been so successful for non-Aboriginal
      infants.

PMID- 16898884
TI  - Risk factors for reduced lung function in Australian Aboriginal children.
AB  - AIM: To determine the influence of perinatal and childhood exposures on lung
      function in a cohort of Australian Aboriginal children. METHODS: This was a cross
      sectional study of 547 Northern Territory Aboriginal children, aged 8-14 years,
      belonging to a birth cohort. Assessment included physical examination and
      spirometry as well as retrospective review of centralised hospital records. The
      effect of select perinatal and childhood exposures on lung function outcomes
      (forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and forced
      expiratory flow between 25 and 75 s (FEF25-75)) adjusted for age, sex, height and
      other measures of size was examined using multiple regression. RESULTS: Non-urban
      residence (FEV1 -5% (95% confidence interval, CI 0.91-0.99), FVC -9% (95% CI 0.87
      0.95)), current cough (FEV1 -6% (95% CI 0.91-0.97), FVC -4% (95% CI 0.93-0.97),
      FEF25-75 -8% (95% CI 0.86-0.98)) and hospitalisations for respiratory disease
      (FEV1 -10% (95% CI 0.86-0.95), FEF25-75 -12% (95% CI 0.70-0.87)) all had
      significant negative effects on adjusted lung function measures. Children with a
      non-Aboriginal ancestor had significantly better lung function. No perinatal
      exposure other than neonatal lung disease had any significant effect on adjusted
      lung function. CONCLUSIONS: For Northern Territory Aboriginal children factors
      related to the childhood environment are more important than perinatal factors in
      determining childhood lung function.

PMID- 16898885
TI  - Audit of feeding practices in babies<1200 g or 30 weeks gestation during the
      first month of life.
AB  - AIM: In 2002, the composition of the breast milk fortifier used in our hospital
      changed, giving increased protein and energy. We therefore decided to
      prospectively audit nutritional management in our unit and to compare nutritional
      intake and growth in our babies with published data. METHODS: Data were
      prospectively collected over a 3-month period on infants<1200 g or 30 weeks
      gestation. Prescribed and delivered volumes of all parenteral and enteral fluids
      were recorded. Babies were weighed as per unit protocol. RESULTS: Thirty-four
      infants met the audit criteria. Data are median (range). After the first week of
      life, energy and protein intakes were 147 (78-174) kcal/kg/day and 3.9 (2.1-4.8)
      g/kg/day respectively. Daily weight gain was 17 (-3.2-35.4) g/kg and was
      significantly associated with both energy and protein intakes (P<0.001). However,
      standard deviation scores for weight fell from 0.15 (-1.9-2.0) at birth to -1.0 (
      2.9-0.8) by 36 weeks corrected age. Time to commencing enteral feeds was 1 (1-3)
      day and to full enteral feeds was 8 (5-28) days. One infant was diagnosed with
      necrotising enterocolitis and eight with chronic lung disease. Mean protein
      intake was significantly lower in babies with chronic lung disease (P=0.005).
      CONCLUSION: Overall, nutritional intakes and weight gain in this cohort of babies
      lie within the recommended ranges, although protein intakes in the smallest
      babies are at the lower end of the range. Enteral feeds are introduced early and
      advanced rapidly, but we have a low incidence of necrotising enterocolitis.
      However, babies still fell across weight centiles, suggesting that actual intakes
      for these tiny babies may be inadequate.

PMID- 16898886
TI  - Post-neonatal mortality by rurality and Indigenous status in Queensland.
AB  - AIM: To compare post-neonatal mortality among urban and rural Indigenous babies
      in Queensland. METHODS: Registrations of deaths at ages 28 days to 12 months were
      linked to routine data from the Queensland Perinatal Data Collection. RESULTS:
      Indigenous babies were 2.52 times more likely to die during the post-neonatal
      period than non-Indigenous babies (95% confidence interval: 1.99, 3.20). The
      differential remained when urban and rural areas were examined separately: the
      differential was 2.53 (1.81, 3.54) in urban areas and 2.26 (1.58, 3.23) in rural
      areas. CONCLUSION: The key demographic variable that determines post-neonatal
      mortality in Queensland is Indigenous status, not rurality. This has important
      policy implications because it means that interventions to reduce the disparity
      in mortality between Indigenous and non-Indigenous babies should be delivered in
      urban as well as rural areas. Better routine data are needed and in particular
      clinical classification of deaths, so that interventions can be monitored and
      avoidable factors identified.

PMID- 16898887
TI  - Broad-range polymerase chain reaction for the diagnosis of Bartonella henselae
      endocarditis.
AB  - We present a case of subacute bacterial endocarditis in a 10-year-old girl with
      Di-George syndrome, congenital heart disease, and mild immunodeficiency. She was
      afebrile at initial presentation but was found to have massive splenomegaly, and
      signs of congestive heart failure. No causative organism could be identified on
      routine blood and tissue cultures. A detailed clinical history revealed a history
      that she had been scratched by a cat and developed intermittant fevers over 3
      months. Bartonella henselae was identified by broad-range 16S r-DNA polymerase
      chain reaction on valvular tissue specimens.

PMID- 16898888
TI  - Methimazole-induced toxic epidermal necrolysis in a 12-year-old girl.
AB  - We report a 12-year-old girl with hyperthyreosis who presented methamazole
      induced toxic epidermal necrolysis (TEN). The patient's past history suggests a
      presence of autoimmune disease. To our knowledge it is the first report
      describing such an adverse effect of methimazole.

PMID- 16898889
TI  - Cross-sensitivity in a child with anticonvulsant hypersensitivity syndrome.
AB  - We describe a fulminant picture of anticonvulsant hypersensitivity syndrome (AHS)
      and the possible role of nitrazepam. A 5-month-old boy developed fever and rash
      after the use of phenobarbitone. Allergy to phenobarbitone was suspected.
      Nitrazepam was substituted for seizure control. Over the next few days he
      progressively collapsed with fever, facial oedema and multi-organ involvement.
      The diagnosis of AHS was delayed because nitrazepam has not been implicated in
      the development of cross-sensitivity. AHS is a severe multi-organ reaction to
      aromatic anti-epileptic drugs. It has been thought to occur as a consequence of
      pre-existing pharmacogenetic and immunologic abnormalities. Careful selection of
      anti-epileptic drugs is essential as cross-sensitivity is common. Intermittent
      benzodiazepines have been recommended in managing breakthrough seizures in AHS.
      However, the structure of benzodiazepines contains aromatic rings and potential
      cross-reactivity cannot be totally ignored. Although we do not have direct proof,
      we believe that nitrazepam prolonged the clinical course.

PMID- 16898890
TI  - Aorta coarctation presenting with intracranial aneurysm rupture.
AB  - Most vascular diseases have a tendency to affect both heart and the brain.
      Intracranial aneurysms are more often found in patients with aorta coarctation
      than in general population, and aneurysm rupture occurs much earlier in these
      patients. Here, we report a case of aorta coarctation which was diagnosed with
      its cerebrovascular complications. Before presenting with cerebrovascular
      complications, the disease can easily be diagnosed with physical examination and
      non-invasive radiological investigations like echocardiography or cardiac
      magnetic resonance imaging.

PMID- 16898891
TI  - Plight of foster children.

PMID- 16898892
TI  - Can sunlight exposure affect early breastfeeding cessation?

PMID- 16898895
TI  - A review of the European Directive for prescribing systemic isotretinoin for acne
      vulgaris.
AB  - Since the introduction of generic oral isotretinoin there have been discussions
      around harmonizing the summary of product characteristics of each formulation. As
      a result of these discussions, a European Directive concerned with the
      prescribing of oral isotretinoin has been introduced and the FDA (Food and Drugs
      Administration) has recently implemented new regulations. The aims of this
      article are to summarize the history of the processes involved, outline the new
      recommendations and discuss the impact of these changes in clinical practice.

PMID- 16898897
TI  - The safety of hydroquinone.
AB  - Hydroquinone is one of the most effective molecules for the treatment of
      hyperpigmentary disorders, with over 40 years of efficacy and safety data.
      Concerns over its safety have been raised because of the fact that it is a
      derivative of benzene and because of the long-term side-effects observed with
      cosmetic products containing high concentrations of hydroquinone. However,
      despite 40-50 years use of hydroquinone for medical conditions, there has not
      been a single documented case of either a cutaneous or internal malignancy
      associated with this drug. This article reviews the evidence for the safety of
      hydroquinone in the treatment of hyperpigmentation conditions.

PMID- 16898898
TI  - Cryotherapy in the treatment of pyogenic granuloma.
AB  - BACKGROUND: Pyogenic granuloma is a benign, acquired, proliferative vascular
      lesion of the skin and mucous membranes. Many different treatments have been used
      for pyogenic granuloma with variable success rates. OBJECTIVE: To evaluate the
      efficacy of cryotherapy in the treatment of pyogenic granuloma. METHODS: In a
      prospective observational study, 135 patients with pyogenic granuloma were
      treated with cryotherapy using liquid nitrogen. The patients were followed up
      every 3 weeks until 3 months after disappearance of the lesion. RESULTS: Complete
      resolution of the pyogenic granuloma was achieved in all patients after a mean of
      1.58 treatments (range, 1-4 treatments). At the end of follow-up period, there
      was a flat imperceptible scar, smaller than the treated lesion, in 16 patients
      (11.8%). A hypertrophic scar, 3 mm in diameter, was observed in one patient.
      Hypopigmentation was observed in seven patients (5.1%). No other complication or
      side-effect was recorded in the study. CONCLUSIONS: We believe that pyogenic
      granuloma can be treated simply and effectively with cryotherapy.

PMID- 16898900
TI  - Onychomycosis in Icelandic children.
AB  - BACKGROUND: Onychomycosis is a rare disorder in children. Few studies exist on
      the incidence or prevalence of onychomycosis in children. OBJECTIVE: To examine
      the epidemiology of childhood onychomycosis in Iceland during the period 1982
      2000. METHODS: Results from all mycological samples taken from children in
      Iceland from 1982 to 2000 were examined. Information about the requesting
      physician, unique social security number, date of birth, sex, results of culture
      and microscopy were registered. Growth of a dermatophyte was taken as an
      indication of a case of onychomycosis. RESULTS: During the period 1982-2000 a
      total of 493 samples from 408 Icelandic children, aged 0-17 years, were examined.
      Dermatophytes were cultured from 148 (30.0%) samples. During the period 1982-85,
      the mean annual incidence of positive cultures was 1.65 per 100,000, increasing
      to 21.30 per 100,000 for the years 1996-2000. Trichophyton rubrum was the
      dominating organism and was found in 102/148 cases positive for the growth of a
      dermatophyte. The incidence of positive dermatophyte cultures increased with age
      and was found in eight children aged 0-4, and in 57 children aged 10-14 years.
      CONCLUSION: Onychomycosis is rare in children, but increases with age. It seems
      that onychomycosis increased during the study period, but it is not clear if this
      was due to a true increase in the prevalence of onychomycosis or an increased
      awareness of onychomycosis, or both.

PMID- 16898899
TI  - Epidermal thickness assessed by optical coherence tomography and routine
      histology: preliminary results of method comparison.
AB  - BACKGROUND: Optical coherence tomography (OCT) is a promising non-invasive
      imaging technique for studying the epidermis and upper dermis in vivo. As
      proposed previously by Welzel et al. (J Am Acad Dermatol 1997; 37: 958-963),
      distance measurements between the entrance peak and the second peak of the A-scan
      seem to correspond to epidermal thickness (ET). However, there is a lack of
      systematic studies comparing OCT with histology. METHODS: Sixteen healthy
      subjects were included in this pilot study. OCT assessments were conducted on the
      upper back. To determine ET by OCT, the distance between the entrance peak and
      the second peak of the A-scan was calculated (ET-OCT). After OCT measurement a 4
      mm punch biopsy was taken on each subject from the same site previously assessed.
      The maximum thickness of the epidermis (ET-Histo) was determined microscopically
      using routine histological slices (formalin-paraffin technique, haematoxylin
      eosin staining). Correlation and agreement between the two methods were assessed
      by means of the Pearson correlation procedure and Bland-Altman plots,
      respectively. RESULTS: ET-Histo was 79.4 +/- 21.9 microm, including a stratum
      corneum thickness of 20 +/- 12.1 microm. OCT measurements resulted in an ET of
      106 +/- 15.4 microm. No correlation between ET-Histo and ET-OCT was observed (r =
      0.29, P = 0.27). There was a considerable lack of agreement between histology and
      OCT measurements as expressed in a high bias of 26.63 microm [95% confidence
      interval (CI) 14.49-38.77]. Furthermore, the lower 95% limits of agreement were 
      18.03 microm (95% CI -37.11 to 1.05) and the upper 95% limits of agreement were
      71.28 microm (95% CI 52.2-90.36) indicating that ET-OCT may be 71.28 microm above
      or 18.03 microm below ET-Histo. CONCLUSIONS: Our preliminary data suggest that
      the above-described OCT algorithm is probably not a valid measure for the
      evaluation of ET. The second peak of the A-scan seems not to correspond to the
      dermo-epidermal junction zone, but rather to fibrous structures in the upper
      dermis. Nevertheless, further systematic comparison studies between OCT and
      histology are warranted, using different OCT algorithms for ET determination and
      cryopreparation, which has a higher reliability than the formalin-paraffin
      technique.

PMID- 16898901
TI  - Assessment of psychological aspects during systemic provocation tests in patients
      with pseudoallergic drug reactions.
AB  - BACKGROUND: Basic mechanisms of pseudoallergic drug reactions as well as a
      possible role of the psyche are currently unknown. OBJECTIVE: Examination of
      psychological status and reactions during diagnostic provocation tests in
      patients with previous pseudoallergic reactions to drugs. SUBJECTS AND METHODS:
      Ten inpatients, admitted for provocation tests, were studied in a double-blind,
      placebo-controlled setting, with inventories of anxiety and depression being
      measured at baseline and psychological reactions and symptoms being recorded
      daily by patients and the attending physician. RESULTS: Patients reported more
      than twice as many symptoms as the physician, independent of the type of
      exposure. While the basic psychological profile of the patients was normal,
      anxiety trait and state values were high during testing, with a significant
      increase depending on whether the patients thought they had received a drug or a
      placebo. Similarly, frequency of symptoms was dependent on the patients'
      perception of the type of exposure. CONCLUSION: These findings demonstrate a high
      level of anxiety during systemic provocation tests in patients with previous
      pseudoallergic drug reactions, raising serious questions as to the diagnostic
      validity of the routine application of this testing.

PMID- 16898902
TI  - Narrowband UVB phototherapy for early-stage mycosis fungoides: evaluation of
      clinical and histopathological changes.
AB  - BACKGROUND: Early-stage (IA, IB, IIA) mycosis fungoides (MF) has long been
      treated with various agents including topical potent steroids, nitrogen mustard,
      carmustine, oral psoralen plus UVA (PUVA), broadband UVB, electron-beam
      radiotherapy, interferon-alpha and retinoids. However, each of these modalities
      is associated with various side-effects. Narrowband UVB (NB-UVB) therapy has the
      same effect but is safer to use than the other methods. OBJECTIVE: Our purpose in
      this prospective study was to determine the effects of NB-UVB in early-stage MF
      both clinically and histopathologically. MATERIALS AND METHODS: Twenty-three
      patients (20 men, three women, aged 27-78 years) with clinically and
      histologically confirmed MF were enrolled. Patients received NB-UVB therapy three
      times a week. Clinical and histological responses, cumulative doses, total number
      of treatments, side-effects and duration of remission period were noted. RESULTS:
      Six patients had stage IA MF, 15 patients stage IB and two patients stage IIA.
      Eighteen patients had patch stage and five patients had plaque stage
      histopathologically. All of the patients in the patch group had a complete
      response (CR). In the plaque group, three patients (60%) had a CR and two (40%)
      had partial (PR) or no clinical response (NR). The clinical response between
      patch and plaque groups was statistically significant. Regarding the
      histopathological findings, 17 (94.4%) had complete clearing and only one (5.6%)
      patient had a partial improvement in the patch group. In the plaque group, one
      (20%) patient had complete clearing and four (80%) patients had partial or no
      improvement. The difference between the two groups was statistically significant.
      In the patch group, the mean cumulative dose was 90.15 J/cm(2) and the mean
      number of treatments was 35.33. In the plaque group, the mean cumulative dose was
      90.67 J/cm(2) and the mean total number of treatments was 39.40. The differences
      were not statistically significant, either between the mean cumulative dose or
      the mean number of treatments. The mean duration of follow-up was 10.87 months
      (range 1-25 months). Only one of the patients had a relapse. CONCLUSIONS: NB-UVB
      therapy for patients with early-stage MF is an effective and safe treatment with
      the effect lasting for months. We suggest that clinical clearance correlates with
      histological improvement except for patients in the plaque stage.

PMID- 16898903
TI  - Prevalence and predictors of psychosocial morbidity in patients with chronic
      pruritic skin diseases.
AB  - BACKGROUND: Itch is a major symptom of many skin diseases and causes patients
      considerable distress, adversely affecting quality of life. Feelings of
      helplessness and lack of control can influence the perceived itch and
      psychosocial complaints. OBJECTIVES: To determine the prevalence of psychosocial
      morbidity among patients with pruritic skin diseases, and the influence of itch
      related variables, coping strategies, and demographic variables on psychosocial
      morbidity. PATIENTS AND METHODS: One hundred and sixty-eight patients with
      pruritic skin diseases from five hospitals in the Netherlands participated in the
      study. Skin-related psychosocial morbidity was measured with the Adjustment to
      Chronic Skin Diseases questionnaire (ACS); general psychosocial morbidity was
      measured with the Symptom Checklist-90 (SCL-90). The frequency and intensity of
      itching and scratching was recorded in diaries. Itch-related coping was measured
      with the Itching Cognitions Questionnaire (ICQ). Multiple regression analyses
      were used. RESULTS: Patients with pruritic skin diseases had higher SCL-90 scores
      than a healthy Dutch population. All patients had psychosocial complaints as
      measured with the ACS. Thirty-nine per cent of the variance in skin-related
      psychosocial morbidity was explained by 'catastrophizing and helpless coping';
      another 11% was explained by itching and scratching. Age and sex together
      explained another 10%. The frequency of itching and scratching (11%),
      'catastrophizing and helpless coping' (19%) and skin-related psychosocial
      morbidity (10%) explained the variance in general psychosocial morbidity.
      CONCLUSIONS: Patients with a pruritic skin disease have a high level of
      psychosocial morbidity. Catastrophizing and helpless coping are the most
      important predictors of psychosocial morbidity, with itching, scratching and
      demographic variables having a limited influence.

PMID- 16898904
TI  - Recurrence of lymphoedema-associated cellulitis (erysipelas) under prophylactic
      antibiotherapy: a retrospective cohort study.
AB  - OBJECTIVE: To identify the predictors of successful antibiotic prophylactic
      treatment using benzathin-penicillin G to prevent recurrence of erysipelas in
      patients with secondary upper limb lymphoedema. DESIGN: A retrospective cohort
      study. SETTING AND PATIENTS: Patients with secondary arm lymphoedema were
      recruited in a single lymphology unit between 1990 and 2003. All patients had had
      at least three recurrences of erysipelas. Patients were given 2.4 MU benzathin
      penicillin G intramuscularly at 14-day intervals. For each patient, the following
      data were recorded: characteristics of breast cancer treatment (type of surgery,
      radiotherapy, hormone therapy), number of erysipelas recurrences before
      inclusion, patient characteristics including body mass index (BMI) and
      lymphoedema volume at inclusion. MAIN OUTCOME MEASURES: The outcome studied was
      the occurrence of erysipelas on the affected arm under antibiotic prophylactic
      treatment. RESULTS: With a 4.2-year median follow-up from the onset of antibiotic
      prophylactic treatment, 23 of 48 women experienced recurrence of erysipelas. The
      median duration of erysipelas recurrence-free period under this treatment was 2.7
      years. The estimated rate of recurrence was 26%[95% confidence interval (CI) 13
      38%] at 1 year and 36% (95% CI 22-50%) at 2 years. No patient stopped the
      treatment because of side-effects. No predictive factor of erysipelas recurrence
      under antibiotic prophylactic treatment was identified. CONCLUSIONS: Antibiotic
      prophylaxis using benzathin-penicillin is a well-tolerated treatment of
      erysipelas recurrence in patients with upper limb lymphoedema secondary to breast
      cancer. The rate of erysipelas recurrence was 26% at 1 year in patients who had a
      history of at least one erysipelas. We did not find any predictor of erysipelas
      recurrence.

PMID- 16898905
TI  - Disappointing results and low tolerability of photodynamic therapy with topical 5
      aminolaevulinic acid in psoriasis. A randomized, double-blind phase I/II study.
AB  - BACKGROUND: Based on good results in the treatment of superficial skin tumours,
      since the early 1990s topical photodynamic therapy with aminolaevulinic acid (ALA
      PDT) has been used for disseminated, inflammatory dermatoses including psoriasis.
      However, there is still a lack of well-documented trials. OBJECTIVE: A
      prospective randomized, double-blind phase I/II intrapatient comparison study was
      conducted in 12 patients to investigate whether topical ALA PDT is an effective
      treatment for chronic plaque-type psoriasis. METHODS: In each patient three
      psoriatic plaques were randomly treated with a light dose of 20 J/cm(2) and 0.1%,
      1% and 5% ALA, respectively. Treatment was conducted twice a week until complete
      clearance or for a maximum of 12 irradiations. Therapeutic efficacy was assessed
      by weekly determination of the psoriasis severity index (PSI). RESULTS: The mean
      percentage improvement was 37.5%, 45.6% and 51.2% in the 0.1%, 1% and 5% ALA
      treated groups, respectively. Irradiation had to be interrupted several times
      because of severe burning and pain sensation. CONCLUSION: Topical ALA PDT did not
      prove to be an appropriate treatment option for plaque-type psoriasis due to
      disappointing clinical efficacy, the time-consuming treatment procedure and its
      unfavourable adverse event profile.

PMID- 16898906
TI  - Vitiligo and ocular findings: a study on possible associations.
AB  - OBJECTIVE: In this study, we aimed to evaluate the ocular findings in vitiligo
      patients and reveal any clinical feature that might suggest an association or a
      risk factor. BACKGROUND: Very few reports in the literature are available about
      the ocular findings in vitiligo and the possible associations of the ocular
      findings in vitiligo patients have not been studied so far. METHODS: A total of
      45 patients with previously documented cutaneous vitiligo were examined for
      ocular findings. Demographic features including age, gender, duration of
      vitiligo, presence of associated autoimmune diseases, type of vitiligo and the
      anatomical distributions of vitiligo were recorded to evaluate a possible
      relationship with the ocular findings. Univariate and multivariate analyses as
      well as cluster analysis were performed. After description of the clusters, the
      Mann-Whitney U-test and Fisher's exact test were used to determine the variables.
      Concordance among the variables in each group was evaluated with the McNemar
      test. RESULTS: Ten patients had ocular findings that included anterior segment
      (iris) involvement, ring-like peripapillary atrophy around the optic nerve,
      atrophy of pigment epithelium, focal hypopigmented spots and diffuse
      hypopigmentation. The presence of periorbital vitiligo was significantly related
      to the ocular findings. Cluster analysis revealed concordances between
      periorbital and genitalial localizations of vitiligo and ocular findings.
      CONCLUSION: The number of patients and the range of ocular findings in our study
      are insufficient to make definite conclusions but anatomical localizations,
      primarily periorbital and to a lesser extent genitalial vitiligo, seem to be the
      most probably alerting features for ocular findings.

PMID- 16898907
TI  - Burden of illness of bacterial cellulitis and erysipelas of the leg in the
      Netherlands.
AB  - BACKGROUND: Information on the prevalence of bacterial cellulitis (BC) and
      erysipelas (ER) of the leg (BCERL) is sparse and dependent on the definitions
      used. There is no information available on the number of hospitalized and non
      hospitalized patients with BCERL, and related treatment costs. OBJECTIVE: The
      purpose of this study was to assess the burden of illness for BCERL in the
      Netherlands in 2001. METHODS: Data were obtained from different linked databases.
      Hospital information was obtained from the National Morbidity Registration (known
      in the Netherlands as the LMR), which includes all Dutch citizens, using ICD-9-CM
      codes. The number of patients not admitted to hospital was estimated using a
      subsample with data from general practitioners (GPs) (N = 50,000). These data
      were extrapolated using age/gender and disease-specific standardization. The
      subsample was used to assess the location of the infection. Reimbursement costs
      were available for all resources. RESULTS: In 2001, approximately 28,000 patients
      presented with either BC or ER of the leg. Of these patients, 2,200 were admitted
      to the hospital and 4-6% had two or more episodes of ER/BC in 2001. The average
      costs per hospitalization for BCERL were 5,346 euros, accumulating to more than
      14 million euros in 2001. Although only 7% of all patients were hospitalized, 83%
      of the total treatment costs could be attributed to hospitalization. CONCLUSIONS:
      BCERL are common and serious infections in the Netherlands. Hospitalization
      occurs in only one in 14 patients but contributes more than 80% of the total
      costs, which accumulate to 17 million euros a year.

PMID- 16898908
TI  - A prospective evaluation of the cost of psoriasis in Spain (EPIDERMA project:
      phase II).
AB  - OBJECTIVE: To estimate the direct and indirect costs related to psoriasis in
      Spain. METHODS: We performed a 12-month, multicentre, prospective longitudinal
      and observational study. Overall expense of care was assessed as the sum of
      direct and indirect costs. RESULTS: A total of 797 patients with varying
      demographics and different degrees of severity of psoriasis were included in the
      study. The mean total cost of psoriasis, including direct and indirect items, was
      1,079 euro per patient and year. The major sources of expenditure were
      prescription drugs (46.6%), followed by medical activities (34.5%). Mean costs in
      patients with moderate and severe psoriasis were approximately 1.5 and 2.5 times
      higher than in those with mild psoriasis, respectively. CONCLUSIONS: In Spain,
      psoriasis is associated with substantial costs both to the National Health System
      and to the patients.

PMID- 16898909
TI  - Expression of sex-determining genes in human sebaceous glands and their possible
      role in the pathogenesis of acne.
AB  - BACKGROUND: The human skin, especially the sebaceous gland, is a steroidogenic
      organ similar to the gonads and adrenal cortex, possessing all the enzymes
      required for steroid sex-hormone synthesis and metabolism. Factors regulating
      cutaneous steroidogenesis associated with disease status remain largely unknown.
      OBJECTIVE: We hypothesized that transcription factors involved in sex formation
      and regulation of steroidogenesis in the classical steroidogenic organs are also
      expressed in the sebaceous glands. Their possible role in the pathogenesis of
      acne were investigated. METHODS: We used reverse transcription polymerase chain
      reaction (RT-PCR), in situ hybridization and Western blotting to analyse the
      expression of SF-1, WT-1, SRY, SOX-9 and DAX-1 mRNAs and their proteins in
      cultured human sebocytes and the facial skin of acne patients. RESULTS: The in
      situ hybridization study showed SOX-9 mRNA mainly localized in basal
      keratinocytes, the basal layer of the sebaceous glands and eccrine glands.
      Immortalized human sebaceous gland cells (SZ95) expressed mRNA for SOX-9, WT-1
      and DAX-1 but not for SF-1 or SRY. The expression of DAX-1 protein was slightly
      inhibited by 10(-6) m oestradiol (E2) at 6 h but enhanced by 10(-6) m
      dihydrotestosterone (DHT) at 48 h. The facial expression of SOX-9 seemed to be
      higher in the acne-prone male patients, while DAX-1 was stronger in subjects
      without acne, although both were statistically insignificant. CONCLUSION: Our
      findings confirm the expression of some sex-determining genes in human sebaceous
      glands. Further studies on a larger patient population including the normal
      controls are needed to elucidate the functional significance of these
      transcription factors in the pathogenesis of acne.

PMID- 16898910
TI  - Comparative efficacy of Hanifin and Rajka's criteria and the UK working party's
      diagnostic criteria in diagnosis of atopic dermatitis in a hospital setting in
      North India.
AB  - BACKGROUND: Diagnosis of atopic dermatitis (AD) depends on clinical features
      because no definitive diagnostic test exists. Criteria proposed by Hanifin and
      Rajka (Acta Derm Venereol (Stockh) 1980; Suppl 92: 44-47) were acceptable for
      hospital-based studies but were found not to be suitable for field studies. A UK
      working party formulated clinical diagnostic criteria that could be used in both
      hospital and epidemiological settings. Validation studies of the criteria showed
      widely variable results, probably due to different clinical settings and
      ethnicity. AIM AND OBJECTIVE: This study was undertaken to validate Hanifin and
      Rajka's criteria and to assess the comparative efficacy of their criteria and the
      UK working party's diagnostic criteria in the diagnosis of AD in a hospital
      setting in North India. SUBJECTS AND METHODS: This study serially included 101
      patients with AD and 48 controls of paediatric age group. The study period was
      from July 2003 to December 2004. RESULTS: Hanifin and Rajka's criteria
      (sensitivity 96%, specificity 93.75%, positive predictive value 97% (PPV) and
      negative predictive value (NPV) 91.84%) had a statistical advantage over the UK
      working party's diagnostic criteria (sensitivity 86%, specificity 95.83%, PPV
      97.75% and NPV 76.67%), with a P-value < 0.005.

PMID- 16898911
TI  - Skin problems after a tsunami.
AB  - BACKGROUND: On December 26, 2004, the biggest earthquake for 40 years, measuring
      9.0 on the Richter scale, triggered a tsunami that pounded the coastal areas of
      South Asia and East Africa. The effects of the tsunami on skin conditions have
      not been evaluated. OBJECTIVE: To determine the influence of the tsunami on skin
      conditions by evaluating the skin problems of patients presenting at hospitals
      after the tsunami. METHODS: Between 5 and 25 January 2005, two dermatologists
      evaluated patients who complained of skin problems at an outpatient clinic and
      emergency room of a general hospital in Banda Aceh, Aceh Province, Indonesia.
      RESULTS: The total number of patients that presented during the study period was
      235 (131 males and 104 females), and they had a total of 265 skin problems. In
      terms of age distribution, most subjects were in their fourth decade (23.0%),
      followed by the third (22.6%) and fifth decade (16.6%). The most prevalent skin
      problems were infections-infestations (32.5%), followed by eczemas (29.8%) and
      traumatic skin disorders (29.4%). In males, traumatic skin disorders were most
      common. The great majority of infection-infestation cases involved superficial
      fungal infections. Contact dermatitis accounted for three-quarters of eczema
      cases, and mainly involved the arms (40.0%) and legs (27.1%). The majority of
      traumatic skin disorders were lacerations, punctures and penetrations, and the
      feet (44.7%) and hands (18.8%) were most frequently affected. CONCLUSIONS:
      Unhygienic conditions, exposure to a hazardous environment and contact with
      various objects during and after the tsunami probably increased the prevalence of
      infections-infestations, traumatic skin disorders and contact dermatitis. To
      prevent these problems and associated secondary bacterial infections, health
      related education and early medical management are required.

PMID- 16898912
TI  - Odontogenic myxoma: a diagnosis to add to the list of facial tumours in infants.
AB  - The differential diagnosis of a midfacial mass in a child includes a great
      variety of tumours. Odontogenic myxoma is a benign tumour arising from the
      mesenchymal portion of the odontogenic apparatus that is usually seen in
      adolescents and adults.

PMID- 16898913
TI  - Ecthyma gangrenosum presenting in diclofenac induced neutropenia.

PMID- 16898914
TI  - Supernumerary breast on the thigh of a woman.

PMID- 16898915
TI  - Photodynamic therapy in a patient with Darier's disease.

PMID- 16898916
TI  - Radiotherapy of T4 squamous cell carcinoma of the skin of nasal pyramid.

PMID- 16898917
TI  - Leiomyosarcoma of the chest wall with cutaneous metastases to the scalp in a
      patient with systemic sclerosis.

PMID- 16898918
TI  - Seborrhoeic keratosis arising on a naevus sebaceous.

PMID- 16898920
TI  - Baseline and stimulated thyroid functions in Behcet's disease.

PMID- 16898919
TI  - Hundreds of basal cell carcinomas in a Gorlin-Goltz syndrome patient cured with
      imiquimod 5% cream.

PMID- 16898921
TI  - Congenital dermatofibrosarcoma protuberans.

PMID- 16898922
TI  - Rhinophyma-like granuloma faciale.

PMID- 16898923
TI  - Analysis of p53 gene mutations in parapsoriasis.

PMID- 16898924
TI  - Arteriovenous haemangioma in chronic liver diseases: case report and
      determination of oestrogen receptor status.

PMID- 16898925
TI  - Extragenital syphilitic chancre manifesting as a solitary nodule of the nipple.

PMID- 16898926
TI  - Chronic hypertrophic acyclovir-resistant genital herpes treated with topical
      cidofovir and with topical foscarnet at recurrence in an HIV-positive man.

PMID- 16898927
TI  - Pseudomonilethrix type II and pili bifurcati.

PMID- 16898928
TI  - Adult-onset Langerhans cell histiocytosis confined to the skin.

PMID- 16898929
TI  - Multiple anaemic macules of the arms: a variant of Bier's spots or naevus
      anemicus?

PMID- 16898930
TI  - Bilateral multiple cutaneous hand metastases of chondrosarcoma.

PMID- 16898931
TI  - Total congenital anonychia in two children of the same family.

PMID- 16898932
TI  - Vaginal adenosis induced by Stevens-Johnson syndrome.

PMID- 16898933
TI  - Efficacy of topical PGE2 in recalcitrant oral lesions of pemphigus vulgaris: a
      clinical trial.

PMID- 16898934
TI  - Genitogluteal porokeratosis.

PMID- 16898935
TI  - Complete remission of a case of classical Kaposi's sarcoma with liposomal
      doxorubicin and radiotherapy.

PMID- 16898936
TI  - Early, continuous, and restorative pain management in injured soldiers: the
      challenge ahead.

PMID- 16898938
TI  - Evaluating chronic pain impact among patients in primary care: further validation
      of a brief assessment instrument.
AB  - OBJECTIVE: To evaluate the psychometric properties of the Profile of Chronic
      Pain: Screen (PCP:S) in primary care. The PCP:S is a brief assessment device
      designed to gauge pain severity, interference, and emotional burden. DESIGN:
      Questionnaire survey with short-term reliability and validity follow-up. METHODS:
      Two hundred and forty-four outpatients (52% female) with chronic pain recruited
      from five primary care settings completed the 15-item PCP:S at an initial testing
      session. Approximately 1 week later, two subgroups participated in a retest
      reliability and validity follow-up. The battery of follow-up questionnaires
      included a measure of social desirability response bias and several instruments
      designed to provide convergent validity for the PCP:S. RESULTS: Retest
      reliability, internal consistency, factor structure, and social desirability bias
      were all found to be acceptable. Likewise, preliminary evidence suggests that, by
      virtue of its correlation with established measures of pain adjustment, the PCP:S
      is a valid pain assessment device. CONCLUSIONS: Although the PCP:S was initially
      developed and validated using a national community sample of adults with chronic
      pain who provided data via telephone interviews, the present findings support its
      use as a brief and psychometrically sound paper-and-pencil measure for the
      assessment of three key components of chronic pain in primary care.

PMID- 16898939
TI  - Underdosing of morphine in comparison with other parenteral opioids in an acute
      hospital: a quality of care challenge.
AB  - OBJECTIVE: We observed that parenteral morphine is routinely prescribed in doses
      that are quite low in relation to doses of alternative parenteral opioids and in
      comparison with published effective doses and guidelines. The present study was
      undertaken to determine: 1) whether different parenteral opioids are dosed
      equivalently; 2) which patient factors affect equianalgesic dose; and 3) which
      patient factors affect opioid choice. DESIGN: At a 750-bed tertiary care,
      teaching hospital in Rochester, NY, patients on the medical and surgical floors
      and in the emergency department who received one or more doses of parenteral
      morphine, hydromorphone, or meperidine were identified using computerized
      pharmacy records. A detailed chart review was performed for each patient,
      recording a variety of patient variables, which were then correlated separately
      with opioid dose and choice. RESULTS: Of the 293 patients treated with boluses of
      a parenteral opioid, 75% received morphine at a median dose of only 2 mg.
      Patients prescribed hydromorphone or meperidine received median equianalgesic
      doses that were 6.7 and 3.4 times higher, respectively. A prescriber's choice of
      opioid affected the equianalgesic dose more significantly than any of the patient
      variables studied, including active home opioid use. CONCLUSIONS: At our
      institution, parenteral morphine boluses are routinely given at relatively low
      doses compared with: 1) other opioids; 2) patient-controlled analgesic dosing; 3)
      usual doses required for analgesia from previous studies; and 4) a historical
      control in the same hospital. The reasons for this pattern are largely
      unexplained by patient variables. Inadequate bolus dosing of morphine may be a
      barrier to appropriate patient analgesia.

PMID- 16898940
TI  - Meta-analysis of the efficacy and safety of intradiscal electrothermal therapy
      (IDET).
AB  - OBJECTIVE: The objective of this study was to determine the representative
      outcomes of the intradiscal electrothermal therapy (IDET) procedure in terms of
      pain relief, reduction of disability, and risk of complications. DESIGN: Meta
      analysis, using a random-effects model. A Medline literature search was conducted
      using search terms associated with the IDET procedure including IDET, intradiscal
      electrothermal therapy, intervertebral disk, and annuloplasty. OUTCOME MEASURES:
      The outcomes analyzed were the visual analog scale (VAS) assessment of pain, the
      bodily pain, and physical functioning subscales of the SF-36 health survey, and
      the Oswestry disability index. RESULTS: From 1998 to March 2005, 62 peer-reviewed
      articles were identified regarding the IDET procedure. Forty-five articles were
      excluded, leaving a total of 17 unique published reports included in this review.
      The overall mean improvement in pain intensity was 2.9 points as measured by the
      VAS. The overall mean improvement in physical function was 21.1 points as
      measured by the SF-36. The overall mean improvement in bodily pain was 18.0
      points as measured by the SF-36. The overall mean improvement in disability was
      7.0 points as measured by the Oswestry disability index. The overall incidence of
      complications was 0.8%. CONCLUSION: Although variation exists in the reported
      outcomes among the various studies of the IDET procedure, the pooled results of
      the published studies provide compelling evidence of the relative efficacy and
      safety of the IDET procedure.

PMID- 16898941
TI  - Pain medicine: palliative care section: a call for more research.

PMID- 16898943
TI  - Toward evidence-based prescribing at end of life: a comparative analysis of
      sustained-release morphine, oxycodone, and transdermal fentanyl, with pain,
      constipation, and caregiver interaction outcomes in hospice patients.
AB  - OBJECTIVE: The primary goal of this investigation was to examine selected
      outcomes in hospice patients who are prescribed one of three sustained-release
      opioid preparations. The outcomes examined include: pain score, constipation
      severity, and ability of the patient to communicate with caregivers. PATIENTS AND
      SETTINGS: This study included 12,000 terminally ill patients consecutively
      admitted to hospices and receiving pharmaceutical care services between the
      period of July 1 and December 31, 2002. DESIGN: We retrospectively examined
      prescribing patterns of sustained-release morphine, oxycodone, and transdermal
      fentanyl. We compared individual opioids on the aforementioned outcome markers,
      as well as patient gender, terminal diagnosis, and median length of stay.
      RESULTS: Patients prescribed a sustained-release opioid had similar average
      ratings of pain and constipation severity, regardless of the agent chosen.
      Patients prescribed transdermal fentanyl were reported to have more difficulty
      communicating with friends and family when compared with patients prescribed
      either morphine or oxycodone. On average, patients prescribed transdermal
      fentanyl had a shorter length of stay on hospice as compared with those receiving
      morphine or oxycodone. CONCLUSION: There was no difference in observed pain or
      constipation severity among patients prescribed sustained-release opioid
      preparations. Patients receiving fentanyl were likely to have been prescribed the
      medication due to advanced illness and associated dysphagia. Diminished ability
      to communicate with caregivers and a shorter hospice course would be consistent
      with this profile. Further investigation is warranted to examine the correlation
      between a patient's ability to interact with caregivers and pain control
      achieved.

PMID- 16898945
TI  - Pain among veterans of Operations Enduring Freedom and Iraqi Freedom.
AB  - OBJECTIVE: Pain is one of the most frequently reported symptoms by veterans
      returning from recent overseas military actions. The purpose of the current study
      was to obtain a preliminary estimate of the prevalence and severity of pain among
      veterans of Operations Enduring Freedom and Iraqi Freedom (OEF/OIF; N=970). The
      demographic, etiologic, and diagnostic characteristics of 100 veterans with
      moderate to severe chronic pain conditions were examined in order to provide a
      description of this new group of pain patients. DESIGN: This was a historical
      cohort study that utilized electronic medical record review for all data
      collection. PATIENTS: All registered OEF/OIF veterans seeking treatment at a
      Southeastern Veterans' Affairs medical center were included in the initial
      cohort. In order to describe the characteristics of those with clinically
      significant pain, 100 veterans were randomly sampled from the subset of patients
      who reported moderate to severe chronic pain intensity during a medical visit
      (N=219). RESULTS: Approximately 47% of veterans whose charts included pain score
      documentation (N=793) reported at least a mild level of current pain. Moderate to
      severe pain intensity was recorded for 28% (N=219) of those in the initial cohort
      with pain scores. Diagnoses of musculoskeletal and connective tissue disorders
      were recorded for 82% of those with chronic conditions (i.e., duration>or=1
      month). CONCLUSIONS: The results of this preliminary study suggest that a
      substantial percentage of OEF/OIF veterans will experience clinically significant
      pain following their military service.

PMID- 16898944
TI  - Responding to challenges in modern combat casualty care: innovative use of
      advanced regional anesthesia.
AB  - BACKGROUND: The war in Iraq has resulted in a high incidence of severe extremity
      injury requiring multiple surgical procedures and extensive rehabilitation. We
      describe the use of advanced regional anesthesia to meet this significant medical
      challenge. METHODS: From March 2003 to December 2004, 4,100 casualties have been
      evacuated to Walter Reed Army Medical Center (WRAMC). Of 1,400 inpatients, 750
      have been battle-injured with 500 having extremity injuries. Of these, 287 (57%)
      received surgical care incorporating regional anesthesia including single
      injection peripheral nerve blocks and continuous peripheral and epidural infusion
      catheters. Wounding, surgical, anesthetic, and outcomes data have been
      prospectively collected. RESULTS: Over 900 operations (mean 4+/-2/patient) were
      performed on 287 casualties prior to arrival at WRAMC, and 634 operations (mean
      2+/-1/patient) were performed at WRAMC. Thirty-five percent of this cohort was
      amputees. In the study group, 646 advanced regional anesthesia procedures,
      including 361 continuous peripheral nerve blocks (CPNBs), were performed with a
      mean catheter infusion time of 9 days (1-34). Catheter-related complications
      occurred in 11.9% of casualties and were technical or minor in nature. Catheter
      related infection rate was 1.9%. In 126 casualties with indwelling CPNB
      catheters, a significant decrease in pain score over 7 days was apparent (mean
      3.7+/-0.2 to 2.2+/-0.2, P<0.001). CONCLUSION: Advanced regional anesthetic
      techniques allowed for safe perioperative surgical anesthesia and analgesia in
      the management of the modern combat casualty.

PMID- 16898946
TI  - Localization of pain and self-reported rape in a female community sample.
AB  - OBJECTIVE: Studies suggest that rape increases risk of medically unexplained pain
      in women. At present it is not clear whether rape is associated with pain at
      specific locations or at multiple locations. In this study we tested the
      hypothesis that rape was associated with a preferential increase in risk of
      pelvic pain that was not explained by pain at other sites. DESIGN: We relied on
      an existing community study that oversampled women with fibromyalgia and major
      depression. Localization was assessed by asking about pain at four sites: pelvic
      region; jaw/face; headache; and lower back. Three groups were identified using a
      structured telephone interview: Abuse Only (sexual/physical abuse excluding
      rape); Rape+Abuse (rape in addition to other sexual/physical abuse); and No
      Abuse. RESULTS: Compared with the No Abuse group, the Rape+Abuse group was eight
      times more likely to have pelvic pain and 3.7 times more likely to have jaw/face
      pain after we controlled for the effect of widespread pain. Rape was not
      associated with lower back pain or headache. The Abuse Only group did not show a
      preferential increase in risk of pain at any of the four locations that were
      assessed. After controlling for pain at other locations, we found that the Rape +
      Abuse group was 10 times more likely to report pelvic pain than the No Abuse
      group (P<0.005). DISCUSSION: In accord with the localization hypothesis, self
      reported rape was uniquely associated with pelvic pain. Future efforts to account
      for pain in the aftermath of rape must specify a mechanism that can
      simultaneously cause widespread pain as well as increase risk of localized pain.

PMID- 16898947
TI  - The risk of action by the Drug Enforcement Administration against physicians
      prescribing opioids for pain.
AB  - OBJECTIVE: Fear of government actions against physicians for prescribing opioids
      for their chronic pain patients is a cause for undertreatment of pain. This study
      was conducted to assess the risk of action by the federal Drug Enforcement
      Administration (DEA). METHODS: The DEA responded to a written request with a list
      of all DEA arrests in fiscal 2003. The Federal Register was reviewed for all
      revocations of DEA registrations for 2003 and 2004. RESULTS: There were 47
      arrests in 2003 from among 963,385 doctors registered with the DEA and 56
      revocations of registration seen in the 2003 and 2004 period. The reasons for
      these actions included loss of medical license, fraud, substance abuse by
      prescriber, sex in exchange for prescriptions, and prescribing without seeing
      patient. For the majority of cases, there was information to believe that a
      documented doctor-patient relationship with a chronic pain patient did not exist.
      CONCLUSION: When adequate documentation exists in the medical record, the risk of
      civil, criminal, or administrative action being taken by the DEA against a
      physician for prescribing opioids for a chronic pain patient is small.

PMID- 16898948
TI  - DEA, administrative action statistics, and pain management: it is time to get
      real.

PMID- 16898949
TI  - Risk of the view through the keyhole: there is much more to physician reactions
      to the DEA than the number of formal actions.

PMID- 16898952
TI  - Practical tip for aging pain specialist.

PMID- 16898950
TI  - Fear and loathing in the pain clinic.

PMID- 16898954
TI  - Platelet nitric oxide synthase is activated by tyrosine dephosphorylation:
      possible role for SHP-1 phosphatase.
AB  - BACKGROUND: Endothelial nitric oxide synthase (eNOS) activity in endothelial
      cells is regulated by post-translational phosphorylation of critical serine,
      threonine and tyrosine residues in response to a variety of stimuli. However, the
      post-translational regulation of eNOS in platelets is poorly defined. OBJECTIVES:
      We investigated the role of tyrosine phosphorylation in the regulation of
      platelet eNOS activity. METHODS: Tyrosine phosphorylation of eNOS and interaction
      with the tyrosine phosphatase SHP-1 were investigated by coimmunoprecipitation
      and immunoblotting. An in vitro immunoassay was used to determine eNOS activity
      together with the contribution of protein tyrosine phosphorylation. RESULTS: We
      found platelet eNOS was tyrosine phosphorylated under basal conditions. Thrombin
      induced a dose- and time-dependent increase in eNOS activity without altering
      overall level of tyrosine phosphorylation, although we did observe evidence of
      minor tyrosine dephosphorylation. In vitro tyrosine dephosphorylation of platelet
      eNOS using a recombinant protein tyrosine phosphatase enhanced thrombin-induced
      activity compared to thrombin alone, but had no effect on endothelial eNOS
      activity either at basal or after stimulation with bradykinin. Having shown that
      dephosphorylation could modulate platelet eNOS activity we examined the role of
      potential protein phosphatases important for platelet eNOS activity. We found SHP
      1 protein tyrosine phosphatase, co-associated with platelet eNOS in resting
      platelets, but does not associate with eNOS in endothelial cells. Stimulation of
      platelets with thrombin increased SHP-1 association with eNOS, while inhibition
      of SHP-1 abolished the ability of thrombin to induce elevated eNOS activity.
      CONCLUSIONS: Our data suggest a novel role for tyrosine dephosphorylation in
      platelet eNOS activation, which may be mediated by SHP-1.

PMID- 16898953
TI  - Multiple B-cell clones producing antibodies directed to the spacer and
      disintegrin/thrombospondin type-1 repeat 1 (TSP1) of ADAMTS13 in a patient with
      acquired thrombotic thrombocytopenic purpura.
AB  - BACKGROUND: The cysteine-rich/spacer domains of ADAMTS13 contain a major binding
      site for antibodies in patients with acquired thrombotic thrombocytopenic purpura
      (TTP). OBJECTIVE: To study the heterogeneity of the antibody response towards
      these domains an immunoglobulin V-gene phage-display library was constructed to
      isolate monoclonal anti-ADAMTS13 antibodies from the immunoglobulin repertoire of
      a patient with acquired TTP. METHODS: Combined variable heavy chain (VH) and
      variable light chain (VL) segments, expressed as single-chain Fv fragments
      (scFv), were selected for binding to an ADAMTS13 fragment consisting of the
      disintegrin/thrombospondin type-1 repeat 1 (TSP1)/cysteine-rich/spacer domains.
      RESULTS: Seven different scFv antibody clones were identified that were assigned
      to four groups based on their homology to VH germline gene segments. Epitope
      mapping revealed that scFv I-9 (VH1-69), I-26 (VH1-02), and I-41 (VH3-09) bind to
      an overlapping binding site in the ADAMTS13 spacer domain, whereas scFv I-16 (VH3
      07) binds to the disintegrin/TSP1 domains. The affinity of scFv for the
      disintegrin/TSP1/cysteine-rich/spacer domain was determined by surface plasmon
      resonance analysis and the dissociation constants ranged from 3 to 254 nM. The
      scFv partially inhibited ADAMTS13 activity. However, full-length IgG prepared
      from the variable domains of scFv I-9 inhibited ADAMTS13 activity more
      profoundly. Plasma of six patients with acquired TTP competed for binding of scFv
      I-9 to ADAMTS13. CONCLUSION: Our data indicate that multiple B-cell clones
      producing antibodies directed against the spacer domain are present in the
      patient analyzed in this study. Our findings also suggest that antibodies with a
      similar epitope specificity as scFv I-9 are present in plasma of other patients
      with acquired TTP.

PMID- 16898955
TI  - Reduced von Willebrand factor-cleaving protease (ADAMTS13) activity in acute
      myocardial infarction.

PMID- 16898957
TI  - Local administration of recombinant human antithrombin in a mouse model of
      peritoneal sepsis.

PMID- 16898956
TI  - Influence of omeprazol on the antiplatelet action of clopidogrel associated to
      aspirin.

PMID- 16898958
TI  - Beta-thalassemia: the Lebanese experience.
AB  - Beta-thalassemia is a hereditary anemia that is quite prevalent in Lebanon. Most
      patients with beta-Thalassemia are treated and followed up mostly at a
      multidisciplinary center, located in the suburban area of Beirut: the Chronic
      Care Center (CCC), operational since 1994. We will review the experience with
      beta-Thalassemia accumulated through this institution. Four hundred and twenty
      five patients, aged 2 to 68 years are followed up at the CCC. Sixty four percent
      have thalassemia major (TM) while 36% have thalassemia intermedia (TI). Lebanese
      patients with TM receive periodic packed red cell transfusions to maintain a pre
      transfusional hemoglobin level of 10 gm/dl at all times and desferrioxamine is
      the standard iron chelator in use. Since 1994, 12 patients with TM have died from
      complications of their disease, with heart failure being responsible for the
      majority of deaths. The incidence of cardiac, endocrinologic, and infectious
      complications will be reviewed. Finally, both current and prospective preventive
      measures will be discussed, specifically educational campaigns and premarital
      screening. The effects of prevention are starting to show as the number of newly
      diagnosed disease is diminishing.

PMID- 16898959
TI  - A sample distribution programme for erythropoietin.
AB  - A survey was sent to laboratories participating in the United Kingdom External
      Quality Assessment Service (UKNEQAS) Haematinics Scheme about the measurement of
      serum erythropoietin (EPO). Six laboratories, from a total of 120 that returned
      the survey, were measuring serum EPO concentrations by commercially available
      immunoassays on site in the United Kingdom. The workload of the laboratories
      varied from up to 100 specimens per month to more than 100 specimens analysed per
      week. All laboratories included control material in the assays and none of the
      laboratories was participating in an external quality assessment scheme for serum
      EPO. Four laboratories agreed to take part in the first sample distribution
      programme, with five and six laboratories participating in distributions 2 and 3
      respectively. The results from eight kits were compared from the three
      distributions over a 2-year period. The serum EPO concentrations for the methods
      showed some variation across the range of 2.9-200 U/l when the serum EPO
      concentrations for each method were compared with the whole method mean. The
      results from this scheme have identified a role for an external quality
      assessment scheme for serum EPO measurements.

PMID- 16898960
TI  - Hydroxyurea therapy increases plasma erythropoietin in patients with essential
      thrombocythaemia or polycythaemia vera.
AB  - The determination of serum/plasma erythropoietin (EPO) concentration has gained
      widespread use in the diagnosis of polycythaemia vera (PV). A reduced EPO
      concentration in a newly diagnosed essential thrombocythaemia (ET) seems to be a
      risk factor for thromboembolic events. In this study plasma EPO concentration was
      determined before and after initiated hydroxyurea (HU) therapy, 14 patients with
      PV or ET were included. After 1 month on HU therapy 11 of 14 patients had
      increased their EPO concentration compared with prior to medication. The plasma
      EPO was increased in all, except one patient, after 4 months HU therapy. If EPO
      is incorporated in the diagnostic or prognostic procedures it should be
      determined before myelosuppressive therapy is initiated.

PMID- 16898961
TI  - Cryoprecipitate production: the use of additives to enhance the yield.
AB  - Cryoprecipitate is still widely used to treat hemophilia A in developing
      countries. However, the yield of factor VIII is relatively low averaging, i.e.
      only 50%. We have attempted to enhance the yield by adding sodium citrate to the
      plasma following the method of Shanbrom and Owens (Blood 98, 2001, 60a). Fresh
      frozen plasma (FFP) units were processed either as control plasma or after the
      addition of 10% sodium citrate. Cryoprecipitate was produced from both. After
      resuspension, calcium chloride was added to the citrated cryoprecipitate to
      correct for excess citrate prior to testing. The levels of FVIII and fibrinogen
      were determined in both preparations. The citrated cryoprecipitates had varying
      yields of fibrinogen and FVIII in the cryoprecipitate. The FVIII levels varied
      from 34% to 215% recovery. Fibrinogen ranged from 55.5% to 121.4%. We found that
      the addition of increasing amounts of CaCl2 to normal plasma raised the FVIII
      values from 1.0 to 4 U/ml. To determine the possibility of assay influence we
      added different quantities of CaCl2 to control plasma and measured the FVIII and
      activated partial thromboplastin time levels. Addition of citrate to plasma
      resulted in an increased total amount of cryoprecipitate much of which was
      citrate. Assays showed considerable ranges in the quantity of FVIII and
      fibrinogen. Activation of FVIII can be caused by addition of excess calcium.

PMID- 16898962
TI  - Quantitation of red cell-bound IgG by an enzyme-linked antiglobulin test in the
      patients with warm-type autoimmune haemolytic anaemia.
AB  - We have previously reported the evaluation of a gel-direct antiglobulin test and
      enzyme-linked antiglobulin test (ELAT) in the laboratory diagnosis of autoimmune
      haemolytic anaemia (AIHA). We now report our experience with quantitative ELAT
      performed on a large group of patients under long-term observation. The number of
      IgG molecules/red blood cell was determined in 658 blood samples from 268
      randomly selected patients with warm-type AIHA. Eighty-six patients were tested
      every 2-4 weeks for several months. Laboratory signs of haemolysis were present
      in 65.7% of blood samples with a small amount of red cell-bound autoantibody (<
      200 IgG molecules/red blood cell) and in 70.4% of blood samples with moderately
      coated red blood cells (200-1000 molecules/red blood cell). Haemolysis was
      demonstrated in 87.9% samples with > 1000 IgG molecules/red blood cell, which
      were predominantly IgG3 and C3 complement, the qualitative factors that may
      increase haemolysis. In 79% of periodically tested patients, the number of IgG
      autoantibody molecules/red blood cell decreased and this correlated with the
      improvement of haemolysis parameters. The number of IgG molecules varied in 21%
      of AIHAs and was associated with poor prognosis.

PMID- 16898963
TI  - The immature reticulocyte fraction: a negative predictor of the harvesting of
      CD34 cells for autologous peripheral blood stem cell transplantation.
AB  - The optimal time for the harvesting of peripheral blood stem cells following
      chemotherapy and growth factors for autologous transplantation is based on the
      CD34 cell count. In this study, 51 patients having 59 stem cell mobilizations
      were assessed for the timing of the harvest by a CD34 cell count and an immature
      reticulocyte fraction (IRF). Results from 272 preharvest tests showed that when
      the CD34 cells were not harvestable, defined as a CD34 cell count of < 15
      cells/microl, the IRF was always < or = 0.2. A low IRF resulted in a negative
      predictive value of 1 for the harvesting of stem cells. The IRF is therefore a
      valuable negative predictor of the timing of autologous stem cell harvesting.

PMID- 16898965
TI  - Expression of the vascular endothelial growth factor receptors 1 and 2 in acute
      myeloid leukemia: incidence and feasibility of immunohistochemical staining.
AB  - Vascular endothelial growth factor (VEGF) and its receptor tyrosine kinases,
      VEGFR-1 and VEGFR-2, are important therapeutic targets for various cancers
      including AML. Paraffin-embedded bone marrow samples (PE-BM) are, in most cases,
      the only tissue accessible to perform retrospective analyses of novel targets
      such as VEGF and/or its receptors. As a result, it limits our options to
      immunohistochemistry (IHS), or more expensive and less practical techniques such
      as enzyme-linked immunosorbent assay (ELISA) or fluorescence in situ
      hybridization (FISH). We analyzed the feasibility of IHS to measure VEGFR-1 and
      VEGFR-2 expression in 28 AML samples using monoclonal antibodies (moAbs) against
      Flt-1 (VEGFR-1) and KDR/Flk-1 (VEGFR-2). Medical records were reviewed for
      relevant clinical information. Expression of VEGFR-1 (+) and VEGFR-2 (+) were
      seen in 25% (7/28) and 43% (12/28) respectively. Forty-six percent (13/28) were
      dual-negatives for VEGFR-1 and VEGFR-2; 14% (4/28) were dual-positives for VEGFR
      1 and VEGFR-2. An inferior survival was observed in patients whose myeloblasts
      express either VEGFR-1 (+) or VEGFR-2 (+), or both. Determination of expression
      of VEGF receptors (1 and 2) by IHS in PE-BM tissue is feasible. Prospective
      comparison of IHC to flow cytometry or other molecular techniques, and assessment
      of the prognostic significance of VEGF receptors in AML patients is warranted.

PMID- 16898964
TI  - Large variation in t(11;14)(q13;q32) and t(14;18)(q32;q21) translocation product
      size is confirmed by sequence analysis of PCR products.
AB  - Polymerase chain reaction is commonly used to detect t(11;14)(q13;q32) and
      t(14;18)(q32;q21) chromosomal translocations associated with mantle cell lymphoma
      and follicular lymphoma. We tested a total of 482 samples from patients with
      suspected non-Hodgkin's lymphoma and sequenced unusual-sized t(11;14)(q13;q32)
      and t(14;18)(q32;q21) products from 33 of these patients. BCL-1 or BCL-2 gene
      rearrangements were confirmed in 23 of 33 patients (70%). Considerable size
      variation was observed using t(11;14) primers, with MTCA and MTCB t(11;14)
      products ranging from 234 to 934 bp and 143 to 560 bp respectively. Less
      variability was observed for t(14;18) Major Breakpoint Region (MBR) products (100
      252 bp) but Minor Cluster Region (MCR) products ranged from 217 to 498 bp. We
      demonstrate the utility of sequence analysis to confirm unusual-sized
      translocation products and reduce false-positive results because of nonspecific
      amplification.

PMID- 16898966
TI  - Secondary amyloidosis causing nephrotic syndrome in a patient with non-Hodgkin's
      lymphoma: quite a rare diagnosis.
AB  - Secondary amyloidosis is usually a complication of chronic inflammation.
      Amyloidosis cases during the course of non-Hodgkin's lymphoma (NHL) are usually
      of AL-type, only one NHL patient with secondary amyloidosis has been reported.
      Our 79-year-old male patient visited us with multiple lymphadenopathies, and he
      was diagnosed with nodal marginal zone B-cell lymphoma. After four cycles of
      combined chemotherapy; his urea, creatinine levels started to increase and he
      developed nephrotic-range proteinuria. His rectal biopsy demonstrated amyloid
      deposition in submucosal vessel walls. The patient has been under hemodialysis
      for 10 months and his lymphoma is still in partial remission. We presented this
      case because it is the second NHL patient who developed secondary amyloidosis
      during his disease course.

PMID- 16898967
TI  - Gene expression changes in a patient presenting nonleukaemic nasal granulocytic
      sarcoma to acute myelogenous leukaemia using 40 K cDNA microarray.
AB  - This is a case report of granulocytic sarcoma occurring as a nasal lesion prior
      to the onset of acute myelogenous leukaemia (AML). To understand this case in
      more detail, we used 40,000 human cDNA microarray to identify the gene expression
      patterns of nonleukaemic stage bone marrow (BM), AML stage BM and AML stage
      peripheral blood cells and subsequently define the molecular basis of this
      disease progression. Of significance, we have tracked the expression profile of
      BM samples during the course of nonleukaemic to leukaemic progression, and
      identified a number of genes that may account for the growth potential of
      leukaemia cells and indicate poor prognosis of this case.

PMID- 16898968
TI  - Bortezomib in relapsed multiple myeloma complicated by extramedullary
      plasmacytomas.
AB  - A 58-year-old man suffered relapse of multiple myeloma complicated by large intra
      abdominal extramedullary plasmacytomas and severe hepatic impairment secondary to
      biliary obstruction. Previous treatment had included two types of combination
      chemotherapy and high-dose therapy with autologous stem cell transplant.
      Combination therapy with bortezomib and dexamethasone resulted in partial
      response of the plasmacytomas and complete resolution of his hepatic impairment.
      Extramedullary plasmacytomas are rare. This report lends support to the efficacy
      of bortezomib in the treatment of plasmacytoma and describes the safe use of
      bortezomib despite hepatic upset.

PMID- 16898969
TI  - Mild dehydrated hereditary stomatocytosis revealed by marked hepatosiderosis.
AB  - We report a patient in whom hepatosiderosis was diagnosed at the age of 55 years
      and who has since been treated by regular bleeding. The H63D mutation was found
      in the heterozygous state in the HFE gene. No mutation was recorded in the
      SLC11A3 gene (ferroportin). Hepatosiderosis did not seem primary, nevertheless
      its cause long remained elusive. Only 2 years ago did we find the responsible
      condition, a very mildly expressed form of dehydrated hereditary stomatocytosis
      (DHS). This genetic disease is a strongly iron-loading condition. Haemolysis was
      fully compensated. Kalaemia was slightly elevated, suggesting a
      pseudohyperkalaemia that may be associated with DHS. Osmotic gradient
      ektacytometry allowed to assess the diagnosis of DHS. The red cell monovalent Na+
      and K+ concentrations were moderately elevated and reduced respectively. The
      temperature dependence of the ouabain + bumetanide-resistant K+ influx produced a
      shallow slope, above and parallel to the control curve. These features were
      consistent with the diagnosis of DHS. The pronounced hepatosiderosis contrasted
      with the mildly expressed DHS, and with the ferritinaemia that was slightly
      elevated, if at all, prior to bleeding. Bleeding caused ferritinaemia to decrease
      and hepatosiderosis to recede. The whole picture accounts for a misleading
      presentation of DHS, in which the primary condition long remained hidden behind
      one of its remotest complications, hepatosiderosis.

PMID- 16898970
TI  - Oral pharmacologic doses of cobalamin may not be as effective as parenteral
      cobalamin therapy in reversing hyperhomocystinemia and methylmalonic acidemia in
      apparently normal subjects.
AB  - A postmenopausal female evaluated for thrombophilia because of bone infarcts had
      mild hyperhomocysteinemia, which increased when hormone replacement was
      discontinued. Serum folate, cobalamin and methylmalonic acid were normal.
      Compound heterozygosity for C677T/A1298C methylenetetrahydrofolate reductase
      polymorphisms was present but oral folic acid failed to lower homocysteine and
      actually increased methylmalonic acid. Oral cobalamin therapy increased serum
      cobalamin and partially decreased methylmalonic acid but had no effect on
      homocysteine. Homocysteine remained unchanged after 11 months of oral cobalamin,
      folic acid and pyridoxine therapy. However, intramuscular cobalamin promptly
      decreased both metabolites to normal. Thus, parenteral cobalamin therapy may have
      greater metabolic effects than oral vitamin therapy even in apparently normal
      subjects.

PMID- 16898971
TI  - Isolated limb infusion with cytotoxic agent for treatment of localized refractory
      cutaneous T-cell lymphoma.
AB  - We described a 57-yr-old male diagnosed with cutaneous T-cell lymphoma that had
      failed multiple treatment options, as his disease was mainly confined to one
      limb. We attempted a novel approach in this condition using a technique of intra
      arterial limb infusion with cytotoxic agent Melphalan (ILI) which has been proven
      beneficial in management of localised malignant melanoma. This treatment approach
      was well tolerated with mild myelosuppression and moderate limb toxicity.
      However, a significant improvement has been noted in the affected limb. This case
      demonstrated the successful use of isolated limb infusion with Melphalan in the
      management of localised cutaneous T-cell lymphoma. However, this result needs to
      be confirmed and further study is recommended. We are unaware there have been
      similar cases reported in the literature.

PMID- 16898972
TI  - Myelodysplastic syndrome transformed into Acute Lymphoblastic Leukaemia (FAB:L3).
AB  - Myelodysplastic syndrome (MDS) is recognized as a preleukaemic disorder with a
      variable risk of transformation to acute myeloid leukaemia. Usually the blast
      cells in leukaemia are transformed after MDS displays a myeloid phenotype. Even
      though lymphoid progression had been reported previously, most displayed myeloid
      lymphoid hybrid or early B phenotype. We report a case of an elderly man who had
      MDS transformed into Acute Lymphoblastic Leukaemia (ALL:L3) which is a rare
      lymphoid transformation.

PMID- 16898973
TI  - A study to assess patient opinion of safety and efficacy and influences on choice
      of treatment of haemophilia A.

PMID- 16898974
TI  - Early onset multiple alloimmunization (anti-E and anti-Jkb) in a thalassaemic.

PMID- 16898975
TI  - Effectiveness of rituximab as prophylaxis in thrombotic thrombocytopenic purpura.

PMID- 16898977
TI  - Foreword to: Keeping our promises: Research, practice, and policy issues in
      health care reliability. A special issue of Health Services Research.

PMID- 16898978
TI  - Organizational silence and hidden threats to patient safety.
AB  - Organizational silence refers to a collective-level phenomenon of saying or doing
      very little in response to significant problems that face an organization. The
      paper focuses on some of the less obvious factors contributing to organizational
      silence that can serve as threats to patient safety. Converging areas of research
      from the cognitive, social, and organizational sciences and the study of
      sociotechnical systems help to identify some of the underlying factors that serve
      to shape and sustain organizational silence. These factors have been organized
      under three levels of analysis: (1) individual factors, including the
      availability heuristic, self-serving bias, and the status quo trap; (2) social
      factors, including conformity, diffusion of responsibility, and microclimates of
      distrust; and (3) organizational factors, including unchallenged beliefs, the
      good provider fallacy, and neglect of the interdependencies. Finally, a new role
      for health care leaders and managers is envisioned. It is one that places high
      value on understanding system complexity and does not take comfort in
      organizational silence.

PMID- 16898979
TI  - Sensemaking of patient safety risks and hazards.
AB  - In order for organizations to become learning organizations, they must make sense
      of their environment and learn from safety events. Sensemaking, as described by
      Weick (1995), literally means making sense of events. The ultimate goal of
      sensemaking is to build the understanding that can inform and direct actions to
      eliminate risk and hazards that are a threat to patient safety. True sensemaking
      in patient safety must use both retrospective and prospective approach to
      learning. Sensemaking is as an essential part of the design process leading to
      risk informed design. Sensemaking serves as a conceptual framework to bring
      together well established approaches to assessment of risk and hazards: (1) at
      the single event level using root cause analysis (RCA), (2) at the processes
      level using failure modes effects analysis (FMEA) and (3) at the system level
      using probabilistic risk assessment (PRA). The results of these separate or
      combined approaches are most effective when end users in conversation-based
      meetings add their expertise and knowledge to the data produced by the RCA, FMEA,
      and/or PRA in order to make sense of the risks and hazards. Without ownership
      engendered by such conversations, the possibility of effective action to
      eliminate or minimize them is greatly reduced.

PMID- 16898980
TI  - Teamwork as an essential component of high-reliability organizations.
AB  - Organizations are increasingly becoming dynamic and unstable. This evolution has
      given rise to greater reliance on teams and increased complexity in terms of team
      composition, skills required, and degree of risk involved. High-reliability
      organizations (HROs) are those that exist in such hazardous environments where
      the consequences of errors are high, but the occurrence of error is extremely
      low. In this article, we argue that teamwork is an essential component of
      achieving high reliability particularly in health care organizations. We describe
      the fundamental characteristics of teams, review strategies in team training,
      demonstrate the criticality of teamwork in HROs and finally, identify specific
      challenges the health care community must address to improve teamwork and enhance
      reliability.

PMID- 16898982
TI  - Struggling to invent high-reliability organizations in health care settings:
      Insights from the field.
AB  - The Mission of the Agency for Healthcare Research and Quality (AHRQ) has been to
      support and conduct health services research and to disseminate those research
      findings. Recently the Agency has changed its mission to: "Improving the quality,
      safety, efficiency and effectiveness of health care for all Americans." For
      agency personnel working with the topic of patient safety, that change has
      created a need to develop greater awareness of the current patient safety
      initiatives underway at leading health care systems in order to determine where
      AHRQ might best play a role in helping these systems more rapidly adopt new
      practices to improve patient safety. In order to make that determination, AHRQ
      conducted a customer needs assessment of leaders in selected health care systems,
      asking them questions about their current implementation initiatives and their
      perceived needs for continued implementation of patient safety initiatives.
      Although not designed or conducted as a research study, the hour-long interviews
      produced rich insights into the implementation efforts of patient safety
      initiatives. The senior leaders interviewed in each of the health care systems,
      described implementing patient safety initiatives on multiple fronts-in some
      systems as many as 15 initiatives were underway. As the number of initiatives
      attests, there was no lack of knowledge about what patient safety practices
      should be implemented (CPOE, rapid response teams, reduction in surgical site
      infections) rather the major struggle these health care systems faced was the
      "how to" of implementation. Most initiatives were only newly begun, so these
      leaders were not yet confident about what they had learned from these efforts or
      whether they could be sustained over time. These health care systems drew many of
      the ideas for initiatives from outside of health care, for example, the nuclear
      power industry or aviation. The executives expressed concern about a number of
      issues including: how patient safety initiatives should be sequenced, the lack of
      benchmarking data to measure their systems against and the pressing need for IT
      standardization. The insights from this customer needs assessment revealed a
      wealth of implementation knowledge in the field and has led AHRQ to create an
      opportunity for leading edge health care systems to learn from each other via
      learning networks.

PMID- 16898981
TI  - Creating high reliability in health care organizations.
AB  - OBJECTIVE: The objective of this paper was to present a comprehensive approach to
      help health care organizations reliably deliver effective interventions. CONTEXT:
      Reliability in healthcare translates into using valid rate-based measures. Yet
      high reliability organizations have proven that the context in which care is
      delivered, called organizational culture, also has important influences on
      patient safety. MODEL FOR IMPROVEMENT: Our model to improve reliability, which
      also includes interventions to improve culture, focuses on valid rate-based
      measures. This model includes (1) identifying evidence-based interventions that
      improve the outcome, (2) selecting interventions with the most impact on outcomes
      and converting to behaviors, (3) developing measures to evaluate reliability, (4)
      measuring baseline performance, and (5) ensuring patients receive the evidence
      based interventions. The comprehensive unit-based safety program (CUSP) is used
      to improve culture and guide organizations in learning from mistakes that are
      important, but cannot be measured as rates. CONCLUSIONS: We present how this
      model was used in over 100 intensive care units in Michigan to improve culture
      and eliminate catheter-related blood stream infections--both were accomplished.
      Our model differs from existing models in that it incorporates efforts to improve
      a vital component for system redesign--culture, it targets 3 important groups-
      senior leaders, team leaders, and front line staff, and facilitates change
      management-engage, educate, execute, and evaluate for planned interventions.

PMID- 16898983
TI  - Enhancing patient safety through organizational learning: Are patient safety
      indicators a step in the right direction?
AB  - OBJECTIVE: To assess the potential contribution of the Agency for Healthcare
      Research and Quality Patient Safety Indicators (PSIs) to organizational learning
      for patient safety improvement. PRINCIPAL FINDINGS: Patient safety improvement
      requires organizational learning at the system level, which entails changes in
      organizational routines that cut across divisions, professions, and levels of
      hierarchy. This learning depends on data that are varied along a number of
      dimensions, including structure-process-outcome and from granular to high-level;
      and it depends on integration of those varied data. PSIs are inexpensive, easy to
      use, less subject to bias than some other sources of patient safety data, and
      they provide reliable estimates of rates of preventable adverse events.
      CONCLUSIONS: From an organizational learning perspective, PSIs have both
      limitations and potential contributions as sources of patient safety data. While
      they are not detailed or timely enough when used alone, their simplicity and
      reliability make them valuable as a higher-level safety performance measure. They
      offer one means for coordination and integration of patient safety data and
      activity within and across organizations.

PMID- 16898984
TI  - Improving patient safety in hospitals: Contributions of high-reliability theory
      and normal accident theory.
AB  - OBJECTIVE: To identify the distinctive contributions of high-reliability theory
      (HRT) and normal accident theory (NAT) as frameworks for examining five patient
      safety practices. DATA SOURCES/STUDY SETTING: We reviewed and drew examples from
      studies of organization theory and health services research. STUDY DESIGN: After
      highlighting key differences between HRT and NAT, we applied the frames to five
      popular safety practices: double-checking medications, crew resource management
      (CRM), computerized physician order entry (CPOE), incident reporting, and root
      cause analysis (RCA). PRINCIPAL FINDINGS: HRT highlights how double checking,
      which is designed to prevent errors, can undermine mindfulness of risk. NAT
      emphasizes that social redundancy can diffuse and reduce responsibility for
      locating mistakes. CRM promotes high reliability organizations by fostering
      deference to expertise, rather than rank. However, HRT also suggests that
      effective CRM depends on fundamental changes in organizational culture. NAT
      directs attention to an underinvestigated feature of CPOE: it tightens the
      coupling of the medication ordering process, and tight coupling increases the
      chances of a rapid and hard-to-contain spread of infrequent, but harmful errors.
      CONCLUSIONS: Each frame can make a valuable contribution to improving patient
      safety. By applying the HRT and NAT frames, health care researchers and
      administrators can identify health care settings in which new and existing
      patient safety interventions are likely to be effective. Furthermore, they can
      learn how to improve patient safety, not only from analyzing mishaps, but also by
      studying the organizational consequences of implementing safety measures.

PMID- 16898985
TI  - Making noncatastrophic health care processes reliable: Learning to walk before
      running in creating high-reliability organizations.
AB  - Health care clinicians successfully apply proven medical evidence in common
      acute, chronic, or preventive care processes less than 80 percent of the time.
      This low level of reliability at the basic process level means that health care's
      efforts to improve reliability start from a different baseline from most other
      industries, and therefore may require a different approach. This paper describes
      The Institute for Healthcare Improvement's (IHI) current approach to improving
      health care reliability, including a useful nomenclature for levels of
      reliability, and a focus on improving reliability of basic health care processes
      before moving on to more sophisticated high reliability organization concepts.
      Early IHI work with a community of health care reliability innovators has
      identified four themes in health care settings that help to explain at least a
      portion of the gap in process reliability between health care and other
      industries. These include extreme dependence on hard work and personal vigilance,
      a focus on mediocre benchmark outcomes rather than process, great tolerance of
      provider autonomy, and failure to create systems that are specifically designed
      to reach articulated reliability goals. This paper describes our recommendations
      for the initial steps health care organizations' might take, based on these four
      themes, as they begin to move toward higher reliability.

PMID- 16898986
TI  - Fair and just culture, team behavior, and leadership engagement: The tools to
      achieve high reliability.
AB  - BACKGROUND: Disparate health care provider attitudes about autonomy, teamwork,
      and administrative operations have added to the complexity of health care
      delivery and are a central factor in medicine's unacceptably high rate of errors.
      Other industries have improved their reliability by applying innovative concepts
      to interpersonal relationships and administrative hierarchical structures
      (Chandler 1962). In the last 10 years the science of patient safety has become
      more sophisticated, with practical concepts identified and tested to improve the
      safety and reliability of care. OBJECTIVE: Three initiatives stand out as worthy
      regarding interpersonal relationships and the application of provider concerns to
      shape operational change: The development and implementation of Fair and Just
      Culture principles, the broad use of Teamwork Training and Communication, and
      tools like WalkRounds that promote the alignment of leadership and frontline
      provider perspectives through effective use of adverse event data and provider
      comments. METHODS: Fair and Just Culture, Teamwork Training, and WalkRounds are
      described, and implementation examples provided. The argument is made that they
      must be systematically and consistently implemented in an integrated fashion.
      CONCLUSIONS: There are excellent examples of institutions applying Just Culture
      principles, Teamwork Training, and Leadership WalkRounds--but to date, they have
      not been comprehensively instituted in health care organizations in a cohesive
      and interdependent manner. To achieve reliability, organizations need to begin
      thinking about the relationship between these efforts and linking them
      conceptually.

PMID- 16898987
TI  - Commentary--Achieving a high-performance health system: High reliability
      organizations within a broader agenda.

PMID- 16898988
TI  - Longitudinal analyses of risk-disorder pathways: the key to early identification
      and targeted intervention.

PMID- 16898989
TI  - Psychosocial outcomes at 15 years of children with a preschool history of speech
      language impairment.
AB  - BACKGROUND: Evidence suggests there is a heightened risk of psychiatric disorder
      in children with speech-language impairments. However, not all forms of language
      impairment are strongly associated with psychosocial difficulty, and some
      psychiatric disorders (e.g., attention deficit/hyperactivity disorder (ADHD)) are
      more prevalent than others in language-impaired populations. The present study
      assessed the psychosocial adjustment in adolescence of young people with history
      of speech-language impairment, and investigated specific relationships between
      language deficits and psychiatric disorders. METHODS: Seventy-one young people
      (aged 15-16 years) with a preschool history of speech-language impairment were
      assessed using a psychiatric interview (K-SADS) supplemented by questionnaires
      probing social encounters and parental reports of behaviour and attention. Their
      psycho-social adjustment was compared with that of a cross-sectional control
      group of age-matched controls. RESULTS: Overall the rate of psychiatric disorder
      was low in the clinical sample and children whose language delay had resolved by
      5.5 years had a good outcome. For those whose language difficulties persisted
      through the school years, there was a raised incidence of attention and social
      difficulties. These difficulties were partially independent and associated with
      different language profiles. The group with attention problems showed a profile
      of specific expressive language difficulties; the group with social difficulties
      had receptive and expressive language difficulties; and the group with both
      attention and social difficulties was of low IQ with global language
      difficulties. CONCLUSIONS: Amongst children with speech-language delays at 5.5
      years, those with more severe and persistent language difficulties and low
      nonverbal IQ are at higher risk of psychiatric morbidity in adolescence.

PMID- 16898990
TI  - Co-occurrence of conduct disorder and depression in a clinic-based sample of boys
      with ADHD.
AB  - BACKGROUND: Children with attention-deficit/hyperactivity disorder (ADHD) are at
      risk for the development of comorbid conduct disorder (CD) and depression. The
      current study examined potential psychosocial risk factors for CD and depression
      in a clinic-based sample of 203 boys (aged 6-10 years) with ADHD. METHODS: The
      boys and their mothers participated in an evaluation that involved assessments of
      cognitive, behavioral, academic, and family functioning. Potential predictors of
      CD and depression involved four domains: parenting behaviors, family environment,
      academic/cognitive functioning, and peer relations. ADHD groups were defined
      using mother- and teacher-report of DSM-IV symptoms. Mother-ratings of DSM-IV
      symptoms were obtained for a subsample of 91 boys approximately 5 years after the
      initial assessment. RESULTS: For both mother- and teacher-defined ADHD groups,
      social problems were related to depression symptoms; hostile, inconsistent, and
      detached parenting behaviors were related to CD symptoms; and family environment
      characterized by low cohesion, high conflict, and low marital satisfaction was
      related to CD and depression symptoms. For the teacher-defined ADHD group,
      parenting variables also predicted depression symptoms. Academic and cognitive
      variables did not predict CD or depression symptoms when parenting, family, and
      peer relationship variables were taken into account. Depression prospectively
      predicted CD, but not the reverse, and parental hostile control and familial
      conflict prospectively predicted CD for the teacher-defined ADHD group only.
      CONCLUSIONS: Source-specificity is a useful consideration when describing the
      relation of parenting and home environment with CD and depression symptoms in
      boys with ADHD. Intervention efforts that address these parenting, family, and
      peer relationship variables may aid in preventing the development of comorbid
      conditions.

PMID- 16898991
TI  - Teenage mothers' anger over twelve years: partner conflict, partner transitions
      and children's anger.
AB  - BACKGROUND: This study examined the effects of maternal anger, partner
      transitions and partner conflict on later oppositional and angry behavior of the
      children of teenage mothers. METHODS: One hundred and twenty-one teenage women
      were interviewed prior to the birth of the baby and at 3 points subsequently,
      when children were newborn, 7 years old and 12 years old. Child and teacher
      reports of children's oppositional behavior were obtained. RESULTS: Women who
      showed higher levels of anger at Time 1 experienced more conflict with partners
      and more partner transitions over the next 12 years than women with lower levels
      of anger. Partner conflict was a stronger predictor of children's oppositional
      and angry behavior than partner transitions. Maternal anger at Time 1 was
      associated with maternal anger at Time 4 but neither predicted children's
      oppositional behavior at Time 4. CONCLUSION: There was support for the
      theoretical model that suggested that the personality characteristics of teenaged
      mothers confer some of their risk to children through children's exposure to the
      mothers' problematic partner relationships.

PMID- 16898992
TI  - Development of male proactive and reactive physical aggression during
      adolescence.
AB  - BACKGROUND: Different developmental courses have been postulated for proactive
      and reactive aggression. OBJECTIVE: Investigated the developmental course of
      proactive and reactive aggression in a large sample of adolescent boys from low
      socioeconomic areas. METHOD: A dual group-based joint trajectory method was used
      to identify distinct trajectories as well as similarities and differences in
      intra-individual changes. RESULTS: The trajectories for proactive and reactive
      aggression were similar: the majority of individuals followed infrequent and
      desisting trajectories. Contrary to expectations, very few adolescents followed
      trajectories of increasing proactive aggression. Reactive aggression was more
      common than proactive aggression. The overlap in trajectory group membership of
      individuals following trajectories of high peaking proactive and reactive
      aggression was nearly 100%. Across a period of 5 years, the boys on the high
      peaking trajectories were twice as likely to have affiliated with gangs.
      CONCLUSIONS: The developmental courses of proactive and reactive aggression are
      similar during adolescence. Males who tend to frequently use one form of
      aggression throughout adolescence also tend to frequently use the other and are
      at an increased risk for contemporaneous delinquent lifestyles.

PMID- 16898993
TI  - Trajectories of aggression from toddlerhood to age 9 predict academic and social
      functioning through age 12.
AB  - BACKGROUND: Using longitudinal data from the NICHD Study of Early Child Care and
      Youth Development, we examined behavior problems and social and academic outcomes
      from ages 9 through 12 in children classified into five trajectories of physical
      aggression, on the basis of maternal ratings obtained from 24 months through 9
      years (N = 1195). METHODS: Outcome data were obtained from teacher reports,
      observations of children's behavior, and children's self-reports. RESULTS:
      Children on the high-stable aggression trajectory (3% of sample) showed the most
      severe adjustment problems, including poorer social skills, higher levels of
      externalizing problems, and more self-reported peer problems; those on the
      moderate-stable aggression trajectory (15%) showed poor regulation and
      inattention. Although children with moderate levels of early aggression that
      decreased sharply by school entry (12%) appeared well adjusted at follow-up,
      those who showed a low level of stable aggression (25%) evidenced some
      unanticipated social and behavior problems. Children in the contrast group (45%)
      were consistently very low in aggression from toddlerhood onward. CONCLUSIONS:
      Results highlight links between different patterns (stable or decreasing) and
      levels (high, moderate, low, very low) of aggression across childhood and
      children's later adjustment. For example, even quite low aggression that is
      stable appears to be a risk factor for some social problems; in contrast,
      moderate aggression that decreases sharply to no aggression by school entry is
      associated with good adjustment at age 12.

PMID- 16898994
TI  - Terrible ones? Assessment of externalizing behaviors in infancy with the Child
      Behavior Checklist.
AB  - BACKGROUND: This study investigated the occurrence, cross-informant agreement, 1
      year stability, and context characteristics of externalizing behaviors in 12
      month-old children, as compared to 24- and 36-month-olds. METHOD: In a general
      population sample of 786 12-month-olds, 720 24-month-olds, and 744 36-month-olds,
      the CBCL/ 1(1/2)-5 was obtained from mothers and fathers and again one year later
      for a subsample of 307 children. Mothers of 1,831 children also provided complete
      data on child, mother, and family characteristics. RESULTS: Over three-fourths of
      the externalizing behaviors occurred in more than 10% of 12-month-olds, over one
      third of the items in more than 25%. For almost all externalizing behaviors, the
      occurrence was significantly lower in 12-month-olds compared to 24- and 36-month
      old children. Mother-father agreement and 1-year stability of externalizing
      behaviors in 12-month-old children were significant, but generally somewhat lower
      than in 24- and 36-month-olds. Context characteristics were related to
      externalizing behaviors in 12-month-olds as well as in older children. Some
      associations were less pronounced in 12-month-old children, but the overall
      pattern of correlates was similar across age groups. CONCLUSIONS: The results of
      this study show that externalizing behaviors in 12-month-old children merit
      further research and can be assessed with the CBCL in a valid way.

PMID- 16898995
TI  - Nicaraguan Sign Language and Theory of Mind: the issue of critical periods and
      abilities.
AB  - BACKGROUND: Previous studies in the literature report that deaf individuals who
      experience late access to language perform poorly on false belief tests of Theory
      of Mind (ToM) compared with age-matched deaf and hearing controls exposed to
      language early. METHODS: A group of 22 deaf Nicaraguans (aged 7 to 39 years) who
      learned Nicaraguan Sign Language (ISN) at different ages were tested on a false
      belief and a nonverbal cartoon retell task designed to elicit talk about the
      contents of character's mental states. RESULTS: Access to sign language by 10
      years of age with possible advantages in language fluency was a strong predictor
      of performance on both the false belief task and mental state narrative task.
      However, a comparison of performance on the two tests indicated that children and
      adults who learned sign after the age of 10 were still able to demonstrate a more
      general ability to use mental state expressions in narratives. Results are
      discussed in terms of late access to language and critical periods for the
      parallel development of Theory of Mind and language. CONCLUSIONS: The findings
      point to age 10 years as a crucial period when lack of language exposure can lead
      to long-lasting deficits in false belief abilities. Late exposure to sign
      language does not, however, rule out all aspects of the ability to consider
      others' mental states. This paper also highlights the need to take into
      consideration a variety of communication responses when evaluating deaf
      children's ToM reasoning.

PMID- 16898996
TI  - Efficacy of small group reading intervention for beginning readers with reading
      delay: a randomised controlled trial.
AB  - BACKGROUND: This study evaluated the effectiveness of an intervention for reading
      delayed children in Year-1 classes. METHODS: A sample (N = 77) of children drawn
      from 14 schools representing those with the weakest reading skills were randomly
      allocated to one of two groups. A 20-week intervention group received the
      intervention for two consecutive 10-week periods, while a 10-week intervention
      group only received the intervention for the second 10 weeks of the study. The
      programme was delivered in daily 20-minute sessions that alternated between small
      group (N = 3) and individual teaching. The programme combined phoneme awareness
      training, word and text reading, and phonological linkage exercises. RESULTS: The
      children receiving the intervention during the first 10-week period made
      significantly more progress on measures of letter knowledge, single word reading,
      and phoneme awareness than children not receiving the intervention. However, the
      children who only received the intervention during the second 10-week period made
      rapid progress and appeared to catch up with the children who had been given the
      more prolonged intervention. Failure to respond to the intervention was predicted
      by poor initial literacy skills and being in receipt of free school meals.
      CONCLUSION: A reading intervention programme delivered on a daily basis by
      trained teaching assistants is an effective intervention for children who show
      reading delays at the end of their first year in school. However, around one
      quarter of the children did not respond to this intervention and these children
      would appear to need more intensive or more prolonged help to improve their
      reading skills.

PMID- 16898997
TI  - The Croydon Assessment of Learning Study: prevalence and educational
      identification of mild mental retardation.
AB  - BACKGROUND: Mild mental retardation is an enduring and impairing condition. Its
      prevalence has varied widely across different studies from .5 to over 8%, with
      higher rates in completely ascertained samples. The current study estimates the
      prevalence of low IQ in the mental retardation range (intellectual disability) in
      a population sample and examines the factors that relate to educational
      identification. METHOD: A total of 2,730 children in school years 8 and 9
      attending local authority schools were assessed in school with the group
      administered Cognitive Abilities Test (CAT). A sample of 304 pupils at high,
      moderate and low risk of mild mental retardation was selected for in-depth study.
      This included the individually measured full-scale IQ (WISC-III(UK)), the
      Wechsler Quicktest of attainments, the Strengths and Difficulties Questionnaire
      from parents and teachers and an abbreviated version of the Social Communication
      Questionnaire. RESULTS: Of those selected for the in-depth study, 204 (67%)
      participated, with a greater proportion from the low risk group. A range of
      prevalence estimates were calculated using different imputation methods and
      assumptions about individuals not screened. Rates of pupils with WISC IQ < 70
      varied from 5.8% to 10.6%. There were no significant gender differences. In
      contrast to the high prevalence estimates using the WISC, the proportion of
      pupils scoring in the lowest stanine on the CAT was as expected. Only 15% of
      those with IQ < 70 had a statement of special educational needs or attended a
      school for moderate learning difficulties. Behaviour, particularly social
      communication problems, predicted educational identification. CONCLUSIONS: The
      current study produced a high estimate of the prevalence of mild intellectual
      disability based on the WISC but not on the CAT. The findings highlight that the
      majority of mild intellectual disability in the UK would not be detected using
      registers. Cases that are detected by registers are more behaviourally disturbed
      than others.

PMID- 16898999
TI  - Causal connections in the acquisition of an orthographic rule: a test of Uta
      Frith's developmental hypothesis.
AB  - BACKGROUND: In a longitudinal study we tested Frith's causal hypothesis that
      children first gain orthographic knowledge through reading and then later, as a
      consequence, through spelling. METHOD: Children from Years 2 and 3 were tested
      three times over two years on their reading and spelling of pseudo-words which
      conformed to the conditional orthographic rule, the 'final -e' or 'split-digraph'
      rule. RESULTS: Cross-lagged panel correlation analyses suggested that the
      children's success in reading split-digraph words was a causal determinant of
      their learning to use split-digraphs in spelling, in the 7- to 8-year period and,
      with one year-group but not with the other, in the 8- to 9-year period. In the 9-
      to 10-year period children's success in reading no longer seemed to affect their
      spelling. CONCLUSIONS: These results strongly support Frith's causal hypothesis
      about the development of orthographic knowledge.

PMID- 16898998
TI  - Gender disparities in mental health service use of Puerto Rican children and
      adolescents.
AB  - BACKGROUND: Differences in service utilization indicating that boys use more
      mental health services than girls were analyzed to see if they could be explained
      by known correlates of service use. These correlates were arranged into
      individual (severe emotional disturbance, level of impairment and externalizing
      disorders), family (parental education, psychopathology and parental concern) and
      school factors (difficulties with school work). The objectives were to understand
      and identify the factors accounting for gender differences in mental health
      service utilization in order to develop alternatives to promote equity in service
      delivery. METHODS: A representative sample of 1,896 children 4 to 17 years of age
      and their primary caretakers were interviewed for this study. Reports of service
      use were obtained using the Service Assessment for Children and Adolescents.
      Logistic regression was used to assess the relationship between gender and
      service use, adjusting for known correlates. RESULTS: Our results showed that,
      except for impairment, other individual, family and school factors did not
      explain gender differences in service utilization. Males with impairment were
      2.87 times more likely to receive services than impaired females (p <or= .01),
      and this result continued to hold true for impaired undiagnosed boys compared to
      impaired diagnoses-free girls (p <or= .001). CONCLUSIONS: Our findings showed a
      service disparity between impaired boys and girls who did not meet criteria for a
      DSM IV diagnosis, but no observed differences in service use between boys and
      girls who met criteria for severe emotional disturbance (SED). Continued
      investigations are necessary to analyze, assess and understand the different
      circumstances that bring boys and girls into treatment, followed by the
      development of appropriate intervention programs at the school and community
      levels.

PMID- 16899000
TI  - Inner speech impairments in autism.
AB  - BACKGROUND: Three experiments investigated the role of inner speech deficit in
      cognitive performances of children with autism. METHODS: Experiment 1 compared
      children with autism with ability-matched controls on a verbal recall task
      presenting pictures and words. Experiment 2 used pictures for which the typical
      names were either single syllable or multisyllable. Two encoding conditions
      manipulated the use of verbal encoding. Experiment 3 employed a task-switching
      paradigm for which performance has been shown to be contingent upon inner speech.
      RESULTS: In Experiment 1, children with autism demonstrated a lower picture
      superiority effect compared to controls. In Experiment 2, the children with
      autism showed a lower word-length effect when pictures were presented alone, but
      a more substantial word-length effect in a condition requiring overt labelling.
      In Experiment 3, articulatory suppression affected the task-switching performance
      of the control participants only. CONCLUSIONS: Individuals with autism have
      limitations in their use of inner speech.

PMID- 16899001
TI  - The influence of health policy and market factors on the hospital safety net.
AB  - OBJECTIVE: To examine how the financial pressures resulting from the Balanced
      Budget Act (BBA) of 1997 interacted with private sector pressures to affect
      indigent care provision. DATA SOURCES/STUDY SETTING: American Hospital
      Association Annual Survey, Area Resource File, InterStudy Health Maintenance
      Organization files, Current Population Survey, and Bureau of Primary Health Care
      data. STUDY DESIGN: We distinguished core and voluntary safety net hospitals in
      our analysis. Core safety net hospitals provide a large share of uncompensated
      care in their markets and have large indigent care patient mix. Voluntary safety
      net hospitals provide substantial indigent care but less so than core hospitals.
      We examined the effect of financial pressure in the initial year of the 1997 BBA
      on uncompensated care for three hospital groups. Data for 1996-2000 were analyzed
      using approaches that control for hospital and market heterogeneity. DATA
      COLLECTION/EXTRACTION METHODS: All urban U.S. general acute care hospitals with
      complete data for at least 2 years between 1996 and 2000, which totaled 1,693
      institutions. PRINCIPAL FINDINGS: Core safety net hospitals reduced their
      uncompensated care in response to Medicaid financial pressure. Voluntary safety
      net hospitals also responded in this way but only when faced with the combined
      forces of Medicaid and private sector payment pressures. Nonsafety net hospitals
      did not exhibit similar responses. CONCLUSIONS: Our results are consistent with
      theories of hospital behavior when institutions face reductions in payment. They
      raise concern given continuing state budget crises plus the focus of recent
      federal deficit reduction legislation intended to cut Medicaid expenditures.

PMID- 16899002
TI  - The impact of health plan delivery system organization on clinical quality and
      patient satisfaction.
AB  - OBJECTIVES: The purpose of this study was to examine the extent to which measures
      of health plan clinical performance and measures of patient perceptions of care
      are associated with health plan organizational characteristics, including the
      percentage of care provided based on a group or staff model delivery system, for
      profit (tax) status, and affiliation with a national managed care firm. DATA
      SOURCES: Data describing health plans on region, age of health plan, for-profit
      status, affiliation with a national managed care firm, percentage of Medicare
      business, total enrollment, ratio of primary care physicians to specialists, HMO
      penetration, and form of health care delivery system (e.g., IPA, network, mixed,
      staff, group) were obtained from InterStudy. Clinical performance measures for
      women's health screening rates, child and adolescent immunization rates, heart
      disease screening rates, diabetes screening rates, and smoking cessation were
      developed from HEDIS data. Measures of patient perceptions of care are obtained
      from CAHPS survey data submitted as Healthplan Employer Data and Information Set,
      Consumer Assessment of Health Plans 2.0 H. STUDY DESIGN: Multivariate regression
      cross-sectional analysis of 272 health plans was used to evaluate the
      relationship of health plan characteristics with measures of clinical performance
      and patient perceptions of care. PRINCIPAL FINDINGS: The form of delivery system,
      measured by percent of care delivered by staff and group model systems, is
      significantly related (p < or = .05) with four of the five clinical performance
      indices but none of the three satisfaction performance indices. Other variables
      significantly associated with performance were being geographically located in
      the Northeast, having nonprofit status, and for patient satisfaction, not being
      part of a larger insurance company. CONCLUSIONS: These comparative results
      provide evidence suggesting that the type of delivery system used by health plans
      is related to many clinical performance measures but is not related to patient
      perceptions of care. These findings underscore the importance of the form of the
      delivery system and the need for further inquiry that examines the relationship
      between organizational form and performance.

PMID- 16899003
TI  - Effects of compensation methods and physician group structure on physicians'
      perceived incentives to alter services to patients.
AB  - OBJECTIVE: To examine how health plan payment, group ownership, compensation
      methods, and other practice management tools affect physician perceptions of
      whether their overall financial incentives tilt toward increasing or decreasing
      services to patients. DATA SOURCE: Nationally representative data on physicians
      are from the 2000-2001 Community Tracking Study Physician Survey (N=12,406).
      STUDY DESIGN: Ordered and multinomial logistic regression were used to explore
      how physician, group, and market characteristics are associated with physician
      reports of whether overall financial incentives are to increase services,
      decrease services, or neither. PRINCIPAL FINDINGS: Seven percent of physicians
      report financial incentives are to reduce services to patients, whereas 23
      percent report incentives to increase services. Reported incentives to reduce
      services were associated with reports of lower ability to provide quality care.
      Group revenue in the form of capitation was associated with incentives to reduce
      services whereas practice ownership and variable compensation and bonuses for
      employee physicians were mostly associated with incentives to increase services
      to patients. Full ownership of groups, productivity incentives, and perceived
      competitive markets for patients were associated with incentives to both increase
      and reduce services. CONCLUSIONS: Practice ownership and the ways physicians are
      compensated affect their perceived incentives to increase or decrease services to
      patients. In the latter case, this adversely affects perceived quality of care
      and satisfaction, although incentives to increase services may also have adverse
      implications for quality, cost, and insurance coverage.

PMID- 16899004
TI  - Are physician reimbursement strategies associated with processes of care and
      patient satisfaction for patients with diabetes in managed care?
AB  - OBJECTIVE: To examine associations between physician reimbursement incentives and
      diabetes care processes and explore potential confounding with physician
      organizational model. DATA SOURCES: Primary data collected during 2000-2001 in 10
      managed care plans. STUDY DESIGN: Multilevel logistic regressions were used to
      estimate associations between reimbursement incentives and process measures,
      including the receipt of dilated eye exams, foot exams, influenza immunizations,
      advice to take aspirin, and assessments of glycemic control, proteinuria, and
      lipid profile. Reimbursement measures included the proportions of compensation
      received from salary, capitation, fee-for-service (FFS), and performance-based
      payment; the performance-based payment criteria used; and interactions of these
      criteria with the strength of the performance-based payment incentive. DATA
      COLLECTION: Patient, provider group, and health plan surveys and medical record
      reviews were conducted for 6,194 patients with diabetes. PRINCIPAL FINDINGS:
      Without controlling for physician organizational model, care processes were
      better when physician compensation was based primarily on direct salary rather
      than FFS reimbursement (four of seven processes were better, with relative risks
      ranging from 1.13 to 1.23) or capitation (six were better, with relative risks
      from 1.06 to 1.36); and when quality/satisfaction scores influenced physician
      compensation (three were better, with relative risks from 1.17 to 1.26). However,
      these associations were substantially confounded by organizational model.
      CONCLUSIONS: Physician reimbursement strategies are associated with diabetes care
      processes, although their independent contributions are difficult to assess, due
      to high correlation with physician organizational model. Regardless of causality,
      a group's use of quality/satisfaction scores to determine physician compensation
      may indicate delivery of high-quality diabetes care.

PMID- 16899005
TI  - Drug treatment service utilization and outcomes for Hispanic and white
      methamphetamine abusers.
AB  - OBJECTIVE: To examine differences in drug treatment service needs, utilization,
      satisfaction, and outcomes between Hispanic and white methamphetamine (meth)
      abusers. DATA SOURCES: Intake assessments and follow-up interviews of 128
      Hispanic and 371 non-Hispanic white meth abusers admitted during 2000-2001 to 43
      drug treatment programs in 13 counties across California. STUDY DESIGN: A
      prospective longitudinal study comparing ethnic differences in problem severity
      during pre- and posttreatment periods, as well as in services received during
      treatment. DATA COLLECTION/EXTRACTION METHODS: The Addiction Severity Index (ASI)
      was administered at both intake and the 9-month follow-up to assess clients'
      problem severity in a number of domains. Service utilization and satisfaction
      were assessed 3 months following treatment admission. PRINCIPAL FINDINGS:
      Hispanics were less educated and reported more employment difficulties than
      whites. Whites were more likely to be treated in residential programs than
      Hispanics despite similar severity in drug and alcohol use, legal, medical and
      family/social problems, and psychiatric status. Significantly more whites than
      Hispanics received psychiatric services, likely because more of them were treated
      in residential programs. Whites also reported receiving greater numbers of total
      services and services addressing alcohol and psychiatric problems. While no
      ethnic differences were found in treatment satisfaction and several other
      outcomes, Hispanics demonstrated better family and social outcomes than whites.
      CONCLUSIONS: Both Hispanic and white meth abusers improved after treatment,
      although benefits from treatment can be further enhanced if services underscore
      different facets of their psychosocial problems.

PMID- 16899006
TI  - Rural residents with disabilities confront substantial barriers to obtaining
      primary care.
AB  - OBJECTIVE: To learn about the health care experiences of rural residents with
      disabilities. STUDY SETTING: Rural areas in Massachusetts and Virginia. STUDY
      DESIGN: Local centers for independent living recruited 35 adults with sensory,
      physical, or psychiatric disabilities to participate in four focus group
      interviews. DATA COLLECTION METHODS: Verbatim transcripts of interviews were
      reviewed to identify major themes. PRINCIPAL FINDINGS: Interviewees described the
      many well-recognized impediments to health care in rural America; disability
      appears to exacerbate these barriers. Interviewees reported substantial
      difficulties finding physicians who understand their disabilities and sometimes
      feel that they must teach their local doctors about their underlying conditions.
      Interviewees described needing to travel periodically to large medical centers to
      get necessary specialty care. Many are poor and are either uninsured or have
      Medicaid coverage, complicating their searches for willing primary care
      physicians. Because many cannot drive, they face great difficulties getting to
      their local doctor and especially making long trips to urban centers. Available
      public transportation often is inaccessible and unreliable. Physicians' offices
      are sometimes located in old buildings that do not have accessible entrances or
      equipment. Based on their personal experiences, interviewees perceive that rural
      areas are generally less sensitive to disability access issues than urban areas.
      CONCLUSIONS: Meeting the health care needs of rural residents with disabilities
      will require interventions beyond health care, involving transportation and
      access issues more broadly.

PMID- 16899007
TI  - Referrals to high-quality cardiac surgeons: patients' race and characteristics of
      their physicians.
AB  - OBJECTIVE: To examine the referral process to cardiac surgeons in order to
      explain racial disparities in access to high-quality cardiac surgeons. DATA
      SOURCES/STUDY SETTINGS: All white and black Medicare fee-for-service patients
      undergoing coronary artery bypass graft (CABG) surgery in New York State during
      1997-1999. STUDY DESIGN: A retrospective analysis of referral patterns for white
      and black patients in relation to the quality of the cardiac surgeon, measured by
      the surgeon's risk-adjusted mortality rate (RAMR), and in relation to
      characteristics of the physician providing the majority of cardiac care before
      the surgery. The average RAMRs of the surgeons to whom different physicians
      referred patients were compared using t-tests and paired t-tests. A hierarchical
      multivariate regression model was estimated to test hypotheses about the effect
      of physicians' characteristics on referrals of blacks to low-quality surgeons.
      DATA EXTRACTION METHOD: Variables were constructed from Medicare claims.
      PRINCIPAL FINDINGS: The differential in surgeons' quality for white and black
      patients is partially due to the physician providing the majority of cardiac care
      before the surgery. There is both across- and within-physician variation in
      referrals. Of the physician characteristics investigated, only the number of
      black patients referred to CABG and the percent of all cardiac referrals to the
      same hospital decrease the difference in surgeons' quality between whites and
      blacks. CONCLUSIONS: Several different pathways lead blacks to cardiac surgeons
      of lower quality. Further research is needed to understand the causes and inform
      policies designed to minimize disparities in access to high-quality providers.

PMID- 16899008
TI  - State regulation and the delivery of physical therapy services.
AB  - OBJECTIVE: The study purpose was to examine the relationship between state
      regulations of physical therapists (PT) and three dependent variables: physical
      therapist assistant (PTA) utilization more than 50 percent of the time during the
      treatment episode (high PTA utilization), number of visits, and patient self
      reported functional health status (FHS) at discharge. We evaluated regulations
      governing licensure of PTAs, PT/PTA ratio, frequency of PT re-evaluation, and PTA
      supervision. DATA SOURCE: The analytic sample included 63,900 patients from 38
      states drawn from 395 clinics who participated in the Focus on Therapeutic
      Outcomes Inc. (Knoxville, TN) database in 2000 and 2001. STUDY DESIGN: Using a
      Bayesian modeling approach with the Markov Chain Monte Carlo estimation method,
      we fitted separate multilevel multivariate regression models predicting high PTA
      utilization, number of visits, and discharge FHS. DATA COLLECTION METHODS:
      Patients completed FHS surveys at intake and discharge. Clinicians recorded the
      number of visits and percentage of time a patient spent with each provider.
      PRINCIPAL FINDINGS: After controlling for patient, therapist, and clinic
      characteristics, the presence of state regulations regarding PTA supervision was
      not associated with the likelihood of high PTA utilization. High PTA utilization
      and regulations requiring full-time onsite supervision were associated with more
      visits, whereas regulation of PT/PTA ratio was associated with fewer visits.
      Supervisory regulations were associated with better discharge FHS. High PTA
      utilization and use of therapy aides were associated with more visits per episode
      and lower discharge FHS. CONCLUSIONS: The use of care extenders in place of PTs
      is likely to result in less efficient and lower quality care in outpatient
      rehabilitation.

PMID- 16899009
TI  - The effect of state medicaid case-mix payment on nursing home resident acuity.
AB  - OBJECTIVE: To examine the relationship between Medicaid case-mix payment and
      nursing home resident acuity. DATA SOURCES: Longitudinal Minimum Data Set (MDS)
      resident assessments from 1999 to 2002 and Online Survey Certification and
      Reporting (OSCAR) data from 1996 to 2002, for all freestanding nursing homes in
      the 48 contiguous U.S. states. STUDY DESIGN: We used a facility fixed-effects
      model to examine the effect of introducing state case-mix payment on changes in
      nursing home case-mix acuity. Facility acuity was measured by aggregating the
      nursing case-mix index (NCMI) from the MDS using the Resource Utilization Group
      (Version III) resident classification system, separately for new admits and long
      stay residents, and by an OSCAR-derived index combining a range of activity of
      daily living dependencies and special treatment measures. DATA
      COLLECTION/EXTRACTION METHODS: We followed facilities over the study period to
      create a longitudinal data file based on the MDS and OSCAR, respectively, and
      linked facilities with longitudinal data on state case-mix payment policies for
      the same period. PRINCIPAL FINDINGS: Across three acuity measures and two data
      sources, we found that states shifting to case-mix payment increased nursing home
      acuity levels over the study period. Specifically, we observed a 2.5 percent
      increase in the average acuity of new admits and a 1.3 to 1.4 percent increase in
      the acuity of long-stay residents, following the introduction of case-mix
      payment. CONCLUSIONS: The adoption of case-mix payment increased access to care
      for higher acuity Medicaid residents.

PMID- 16899011
TI  - Changes in the use of postacute care during the initial Medicare payment reforms.
AB  - OBJECTIVE: To examine changes in postacute care (PAC) use during the initial
      Medicare payment reforms enacted by the Balanced Budget Act of 1997. DATA
      SOURCES: We used claims data from the 5 percent Medicare beneficiary sample in
      1996, 1998, and 2000. Linked data from the Denominator file, Provider of Service
      file, and Area Resource File provided additional patient, hospital, and market
      area characteristics. STUDY DESIGN: Six disease groups with high PAC use were
      selected for analysis. We used multinomial logit regression to examine how PAC
      use differed by year of service, controlling for patient, hospital, and market
      area characteristics. PRINCIPAL FINDINGS: There were major changes in PAC use,
      and a portion of services shifted to settings where reimbursement remained cost
      based. During the first reform, the home health agency interim payment system,
      home health use decreased consistently across disease groups. This decrease was
      accompanied by increased use in skilled nursing facilities (SNFs). Following the
      implementation of the prospective payment system for SNFs, the use of inpatient
      rehabilitation facilities increased. CONCLUSIONS: The shift in usage among
      settings occurred in two stages that corresponded to the timing of payment
      reforms for home health agencies and SNFs. Evidence strongly suggests the
      substitutability between PAC settings. Financial incentives, in addition to
      clinical needs and individual preferences, play a major role in PAC use.

PMID- 16899012
TI  - A cost analysis of the Iowa Medicaid primary care case management program.
AB  - OBJECTIVE: To determine the cost savings attributable to the implementation and
      expansion of a primary care case management (PCCM) program on Medicaid costs per
      member in Iowa from 1989 to 1997. DATA SOURCES: Medicaid administrative data from
      Iowa aggregated at the county level. STUDY DESIGN: Longitudinal analysis of costs
      per member per month, analyzed by category of medical expense using weighted
      least squares. We compared the actual costs with the expected costs (in the
      absence of the PCCM program) to estimate cost savings attributable to the PCCM
      program. PRINCIPAL FINDINGS: We estimated that the PCCM program was associated
      with a savings of US dollars 66 million to the state of Iowa over the study
      period. Medicaid expenses were 3.8 percent less than what they would have been in
      the absence of the PCCM program. Effects of the PCCM program appeared to grow
      stronger over time. Use of the PCCM program was associated with increases in
      outpatient care and pharmaceutical expenses, but a decrease in hospital and
      physician expenses. CONCLUSIONS: Use of a Medicaid PCCM program was associated
      with substantial aggregate cost savings over an 8-year period, and this effect
      became stronger over time. Cost reductions appear to have been mediated by
      substituting outpatient care for inpatient care.

PMID- 16899013
TI  - Stage of change for making an informed decision about Medicare health plans.
AB  - OBJECTIVE: To assess the applicability of the transtheoretical model of change
      (TTM) to informed choice in the Medicare population. DATA SOURCES/STUDY SETTING:
      Two hundred and thirty-nine new Medicare enrollees randomly selected from the
      Center for Medicare and Medicaid Services' October 2001 Initial Enrollee File, a
      repository of data for persons who are going to turn 65 and become entitled to
      enroll in Medicare in the next 3 months. STUDY DESIGN: Study participants
      completed TTM measures of stage of change, decisional balance, and self-efficacy
      for informed choice, as well as measures of Medicare knowledge, perceived
      knowledge, and information seeking. Model testing was conducted to determine
      whether well-established relationships between stage of change, decisional
      balance, and self-efficacy replicate for informed choice in the Medicare
      population, and whether Medicare knowledge and information-seeking increase
      across the stages. DATA COLLECTION/EXTRACTION METHODS: Survey data were collected
      using mail surveys with telephone follow-up for nonresponders. PRINCIPAL
      FINDINGS: Predicted relationships were established between stage of change for
      informed choice and decisional balance, self-efficacy, Medicare knowledge, and
      information seeking. The amount of variance accounted for by stage of change for
      informed choice was larger than that found for smoking cessation, where the TTM
      has had its greatest successes. CONCLUSIONS: The methods and findings lay the
      groundwork for development of TTM-based interventions for Medicare beneficiaries,
      and provide a prototype for the application of the TTM to informed decision
      making among other types of consumers who are being asked to take more
      responsibility for their health care.

PMID- 16899014
TI  - Development of an easy-to-use Spanish Health Literacy test.
AB  - OBJECTIVE: The study was intended to develop and validate a health literacy test,
      termed the Short Assessment of Health Literacy for Spanish-speaking Adults
      (SAHLSA), for the Spanish-speaking population. STUDY DESIGN: The design of SAHLSA
      was based on the Rapid Estimate of Adult Literacy in Medicine (REALM), known as
      the most easily administered tool for assessing health literacy in English. In
      addition to the word recognition test in REALM, SAHLSA incorporates a
      comprehension test using multiple-choice questions designed by an expert panel.
      DATA COLLECTION: Validation of SAHLSA involved testing and comparing the tool
      with other health literacy instruments in a sample of 201 Spanish-speaking and
      202 English-speaking subjects recruited from the Ambulatory Care Center at UNC
      Health Care. PRINCIPAL FINDINGS: With only the word recognition test, REALM could
      not differentiate the level of health literacy in Spanish. The SAHLSA
      significantly improved the differentiation. Item response theory analysis was
      performed to calibrate the SAHLSA and reduce the instrument to 50 items. The
      resulting instrument, SAHLSA-50, was correlated with the Test of Functional
      Health Literacy in Adults, another health literacy instrument, at r=0.65. The
      SAHLSA-50 score was significantly and positively associated with the physical
      health status of Spanish-speaking subjects (p<.05), holding constant age and
      years of education. The instrument displayed good internal reliability
      (Cronbach's alpha=0.92) and test-retest reliability (Pearson's r=0.86).
      CONCLUSIONS: The new instrument, SAHLSA-50, has good reliability and validity. It
      could be used in the clinical or community setting to screen for low health
      literacy among Spanish speakers.

PMID- 16899015
TI  - Accuracy of hospital report cards based on administrative data.
AB  - CONTEXT: Many of the publicly available health quality report cards are based on
      administrative data. ICD-9-CM codes in administrative data are not date stamped
      to distinguish between medical conditions present at the time of hospital
      admission and complications, which occur after hospital admission. Treating
      complications as preexisting conditions gives poor-performing hospitals "credit"
      for their complications and may cause some hospitals that are delivering low
      quality care to be misclassified as average- or high-performing hospitals.
      OBJECTIVE: To determine whether hospital quality assessment based on
      administrative data is impacted by the inclusion of condition present at
      admission (CPAA) modifiers in administrative data as a date stamp indicator.
      DESIGN, SETTING, AND PATIENTS: Retrospective cohort study based on 648,866
      inpatient admissions between 1998 and 2000 for coronary artery bypass graft
      (CABG) surgery, coronary angioplasty (PTCA), carotid endarterectomy (CEA),
      abdominal aortic aneurysm (AAA) repair, total hip replacement (THR), acute MI
      (AMI), and stroke using the California State Inpatient Database which includes
      CPAA modifiers. Hierarchical logistic regression was used to create separate
      condition-specific risk adjustment models. For each study population, one model
      was constructed using only secondary diagnoses present at admission based on the
      CPAA modifier: "date stamp" model. The second model was constructed using all
      secondary diagnoses, ignoring the information present in the CPAA modifier: the
      "no date stamp model." Hospital quality was assessed separately using the "date
      stamp" and the "no date stamp" risk-adjustment models. RESULTS: Forty percent of
      the CABG hospitals, 33 percent of the PTCA hospitals, 40 percent of the THR
      hospitals, and 33 percent of the AMI hospitals identified as low-performance
      hospitals by the "date stamp" models were not classified as low-performance
      hospitals by the "no date stamp" models. Fifty percent of the CABG hospitals, 33
      percent of the PTCA hospitals, 50 percent of the CEA hospitals, and 36 percent of
      the AMI hospitals identified as low-performance hospitals by the "no date stamp"
      models were not identified as low-performance hospitals by the "date stamp"
      models. The inclusion of the CPAA modifier had a minor impact on hospital quality
      assessment for AAA repair, stroke, and CEA. CONCLUSION: This study supports the
      hypothesis that the use of routine administrative data without date stamp
      information to construct hospital quality report cards may result in the mis
      identification of hospital quality outliers. However, the CPAA modifier will need
      to be further validated before date stamped administrative data can be used as
      the basis for health quality report cards.

PMID- 16899016
TI  - Date stamping: will it withstand the test of time?

PMID- 16899017
TI  - Health care organizations' use of data on race/ethnicity to address disparities
      in health care.

PMID- 16899018
TI  - Addressing racial and ethnic disparities in health care: using federal data to
      support local programs to eliminate disparities.
AB  - To reduce racial and ethnic disparities in health care, managers, policy makers,
      and researchers need valid and reliable data on the race and ethnicity of
      individuals and populations. The federal government is one of the most important
      sources of such data. In this paper we review the strengths and weaknesses of
      federal data that pertain to racial and ethnic disparities in health care. We
      describe recent developments that are likely to influence how these data can be
      used in the future and discuss how local programs could make use of these data.

PMID- 16899019
TI  - Using a Spanish surname match to improve identification of Hispanic women in
      Medicare administrative data.
AB  - OBJECTIVE: To assess the effectiveness of a Spanish surname match for improving
      the identification of Hispanic women in Medicare administrative data in which
      Hispanics are historically underrepresented. DATA SOURCES: We collected self
      identified race/ethnicity data (N=2,997) from a mailed survey sent to elderly
      Medicare beneficiaries who resided in 11 geographic areas consisting of eight
      metropolitan counties and three nonmetropolitan areas (171 counties) in the fall
      of 2004. The 1990 Census Spanish Surname list was used to identify Hispanics in
      the Medicare data. In addition, we used data published on the U.S. Census Bureau
      website to obtain estimates of elderly Hispanics. STUDY DESIGN: We used self
      identified race/ethnicity as the gold standard to examine the agreement with
      Medicare race code alone, and with Medicare race code+Spanish surname match.
      Additionally, we estimated the proportions of Hispanic women and men, in each of
      the 11 geographic areas in our survey, using the Medicare race code alone and the
      Medicare race code+Spanish surname match, and compared those estimates with
      estimates derived from U.S. Census 2000 data. PRINCIPAL FINDINGS: The Spanish
      surname match dramatically increased the accuracy of the Medicare race code for
      identifying both Hispanic and white women, producing improvements comparable with
      those seen for men. CONCLUSIONS: We recommend the addition of a proxy race code
      in the Medicare data using the Spanish surname match to improve the accuracy of
      racial/ethnic representation.To assess the effectiveness of a Spanish surname
      match for improving the identification of Hispanic women in Medicare
      administrative data in which Hispanics are historically underrepresented. We
      collected self-identified race/ethnicity data (N=2,997) from a mailed survey sent
      to elderly Medicare beneficiaries who resided in 11 geographic areas consisting
      of eight metropolitan counties and three nonmetropolitan areas (171 counties) in
      the fall of 2004. The 1990 Census Spanish Surname list was used to identify
      Hispanics in the Medicare data. In addition, we used data published on the U.S.
      Census Bureau website to obtain estimates of elderly Hispanics. We used self
      identified race/ethnicity as the gold standard to examine the agreement with
      Medicare race code alone, and with Medicare race code+Spanish surname match.
      Additionally, we estimated the proportions of Hispanic women and men, in each of
      the 11 geographic areas in our survey, using the Medicare race code alone and the
      Medicare race code+Spanish surname match, and compared those estimates with
      estimates derived from U.S. Census 2000 data. The Spanish surname match
      dramatically increased the accuracy of the Medicare race code for identifying
      both Hispanic and white women, producing improvements comparable with those seen
      for men. We recommend the addition of a proxy race code in the Medicare data
      using the Spanish surname match to improve the accuracy of racial/ethnic
      representation.

PMID- 16899021
TI  - Obtaining data on patient race, ethnicity, and primary language in health care
      organizations: current challenges and proposed solutions.
AB  - OBJECTIVES: To provide an overview of why health care organizations (HCOs) should
      collect race, ethnicity, and language data, review current practices, discuss the
      rationale for collecting this information directly from patients, and describe
      barriers and solutions. PRINCIPAL FINDINGS: Hospitals and HCOs with data from
      their own institutions may be more likely to look at disparities in care, design
      targeted programs to improve quality of care, and provide patient-centered care.
      Yet data collection is fragmented and incomplete within and across organizations.
      A major factor affecting the quality of data is the lack of understanding about
      how best to collect this information from patients. CONCLUSIONS: If HCOs make a
      commitment to systematically collect race/ethnicity and language data from
      patients, it would be a major step in enhancing the ability of HCOs to monitor
      health care processes and outcomes for different population groups, target
      quality initiatives more efficiently and effectively, and provide patient
      centered care.

PMID- 16899020
TI  - Use of geocoding and surname analysis to estimate race and ethnicity.
AB  - OBJECTIVE: To review two indirect methods, geocoding and surname analysis, for
      estimating race/ethnicity as a means for health plans to assess disparities in
      care. STUDY DESIGN: Review of published articles and unpublished data on the use
      of geocoding and surname analyses. PRINCIPAL FINDINGS: Few published studies have
      evaluated use of geocoding to estimate racial and ethnic characteristics of a
      patient population or to assess disparities in health care. Three of four studies
      showed similar estimates of the proportion of blacks and one showed nearly
      identical estimates of racial disparities, regardless of whether indirect or more
      direct measures (e.g., death certificate or CMS data) were used. However,
      accuracy depended on racial segregation levels in the population and region
      assessed and geocoding was unreliable for identifying Hispanics and
      Asians/Pacific Islanders. Similarly, several studies suggest surname analyses
      produces reasonable estimates of whether an enrollee is Hispanic or Asian/Pacific
      Islander and can identify disparities in care. However, accuracy depends on the
      concentrations of Asians or Hispanics in areas assessed. It is less accurate for
      women and more acculturated and higher SES persons due intermarriage, name
      changes, and adoption. Surname analysis is not accurate for identifying African
      Americans. Recent unpublished analyses suggest plans can successfully use a
      combined geocoding/surname analyses approach to identify disparities in care in
      most regions. Refinements based on Bayesian methods may make geocoding/surname
      analyses appropriate for use in areas where the accuracy is currently poor, but
      validation of these preliminary results is needed. CONCLUSIONS: Geocoding and
      surname analysis show promise for estimating racial/ethnic health plan
      composition of enrollees when direct data on major racial and ethnic groups are
      lacking. These data can be used to assess disparities in care, pending
      availability of self-reported race/ethnicity data.

PMID- 16899022
TI  - Looking forward: cross-cutting issues in the collection and use of racial/ethnic
      data.
AB  - Availability of reliable and valid race/ethnicity data is essential for
      monitoring and improving quality of care for minority groups. We explore the
      limitations and challenges posed by existing means of data collection and discuss
      issues that need to be considered as the data are analyzed and used.

PMID- 16899023
TI  - Genetic polymorphisms in the MMP-1 and MMP-3 gene may contribute to chronic
      periodontitis in a Brazilian population.
AB  - OBJECTIVES: Matrix metalloproteinase-1 and -3 (MMP-1, MMP-3) represent
      proteinases that degrade macromolecules of the extracellular matrix. These
      enzymes play a fundamental role during destruction of periodontal tissues.
      Genetic polymorphisms were characterized in the promoter region of the MMP-1 and
      MMP-3 genes. The aim of this study was to investigate the relationship between
      these genetic variations with chronic periodontitis in a Brazilian population.
      MATERIAL AND METHODS: Non-smoking subjects (n = 114) exhibiting sites > or = 5 mm
      clinical attachment loss were recruited for study. Control subjects (n = 109)
      should not exhibit clinical signals of periodontitis. MMP-1 (-1607 1G/2G, -519
      A/G) and MMP-3 (-1612 5A/6A) gene promoter polymorphisms were genotyped using PCR
      RFLP methods. RESULTS: Analysis of polymorphisms showed no differences in
      distribution of the -1607 1G/2G and -519 A/G variants in the MMP-1 gene between
      the healthy and periodontitis group (p > 0.05). However, the distribution of
      genotype frequencies of the -1612 5A/6A polymorphism in the MMP-3 gene showed
      that the 5A/5A genotype was significantly more frequent in the periodontitis
      group (p = 0.008). The same was not observed in the 5A/6A genotype once only one
      5A allele is carried. We also observed a trend to increase the frequency of the
      MMP-1/MMP-3 haplotype (2G/5A) in the periodontitis group (p = 0.08). CONCLUSION:
      On the basis of the results, no significant association is found for the MMP-1
      polymorphisms with susceptibility of periodontitis, while the MMP-3 gene
      polymorphism may contribute to periodontal tissue destruction during
      periodontitis in Brazilian subjects.

PMID- 16899024
TI  - Interleukin-6 receptor gene polymorphisms and periodontitis in a non-smoking
      Japanese population.
AB  - AIM: The indispensable role of interleukin-6 receptor (IL-6R) in regulating IL-6
      responses has been clearly established. We have previously reported that IL6R
      polymorphisms strongly influenced the serum levels of soluble IL-6R. In this
      study, we investigated the association between these genetic variations and
      periodontitis. MATERIAL AND METHODS: Among the seven novel IL6R single-nucleotide
      polymorphisms (SNPs) reported, we genotyped two important sites: the +48892 A/C
      in exon 9 and the -183 G/A in the promoter region. The SNP in exon 9 results in
      Asp-->Ala substitution in the proteolytic cleavage site of IL-6Ralpha. In total,
      212 periodontitis cases and 210 healthy controls were genotyped using polymerase
      chain reaction, restriction fragment length polymorphisms and direct sequencing
      methods. RESULTS: Analysis of the genotype distribution of the +48892 A/C SNP in
      periodontitis patients and in controls revealed a suggestive association with
      aggressive (p = 0.04) and chronic periodontitis (p = 0.04). In addition, the
      carriage rate for the A allele was significantly higher in chronic periodontitis
      patients [p = 0.02, odds ratio (OR) = 2.25]. No association was found in the -183
      G/A SNP. The two markers were in linkage disequilibrium (LD) (|D'| = 0.53).
      CONCLUSION: The IL6R+48892 A/C polymorphism could act as a risk factor for
      periodontitis; however, further association and biological studies are needed.

PMID- 16899025
TI  - Proportion of antibiotic resistance in subgingival plaque samples from Mexican
      subjects.
AB  - AIM: To determine the proportion of bacteria resistant to amoxicillin and
      doxycycline in subgingival plaque samples from Mexican subjects. MATERIALS AND
      METHODS: Two subgingival plaque samples were taken from 20 Mexican subjects.
      Samples were dispersed, diluted and plated on non-antibiotic agar plates and on
      plates containing 0.5, 1, 2, 4, 8 and 16 microg/ml of either amoxicillin or
      doxycycline. The proportion of resistant bacteria was calculated based on the
      total number of colony-forming units present in the non-antibiotic containing
      plates. RESULTS: On average, 0.4-13.4% and 0.9-20.4% of the total cultivable
      subgingival microbiota was resistant to the concentrations tested of amoxicillin
      and doxycycline, respectively. The differences between antibiotics were
      statistically significant for the 0.5, 2 and 4 mug/ml concentrations (p < 0.05,
      Wilcoxon's test). CONCLUSIONS: Our findings revealed that a relatively small
      proportion of the total cultivable subgingival microbiota from Mexican subjects
      was resistant to amoxicillin and doxycycline.

PMID- 16899026
TI  - The effect of toothbrushing regimens on the plaque inhibitory properties of an
      experimental cetylpyridinium chloride mouthrinse.
AB  - OBJECTIVE: The objective of this study was to determine the effect of various
      toothbrushing regimens with a standard fluoride dentifrice on the plaque
      inhibitory properties of an alcohol-free, high bioavailable 0.07% cetylpyridinium
      chloride (CPC) mouthrinse. MATERIALS AND METHODS: The study was a randomized,
      single-centre, examiner blind, four-period cross-over study involving 29 healthy
      subjects. Four treatment regimens were evaluated: (1) Toothbrushing with
      dentifrice followed by a water rinse (B-W, negative control); (2) Toothbrushing
      with dentifrice followed by a CPC mouthrinse use (B-CPC); (3) Toothbrushing with
      dentifrice followed by a water rinse and then a CPC mouthrinse use (B-W-CPC); and
      (4) Toothbrushing with dentifrice and waiting 60 min. prior to a CPC mouthrinse
      use (B-60 min.-CPC). Three days before the baseline exam of treatment periods,
      subjects were instructed to brush only the lingual surfaces of their teeth for up
      to 60 s twice daily. At baseline, subjects received a plaque exam using the
      Turesky modification of the Quigley-Hein index (MQH) followed by a polishing on
      the lingual and buccal surfaces of their teeth. During treatment periods,
      subjects were asked to brush only the lingual surfaces of their teeth with a
      standard fluoride dentifrice. Rinsing with 20 ml of the experimental CPC solution
      was done for 30 s twice daily. The evening before the last day of treatment
      periods (Day 4), subjects were asked to refrain from any oral hygiene, eating,
      and drinking after brushing. On Day 4, plaque was scored using the MQH Index. A
      10-day wash-out of normal oral hygiene was allowed between each of the four
      treatment periods. The data were analysed using analysis of covariance for cross
      over designs. RESULTS: Twenty-five to 29 subjects were evaluable at any given
      visit. With respect to unbrushed buccal and brushed lingual surfaces, all three
      CPC regimens had highly significantly (p < or = 0.0006) lower mean plaque scores
      than the B-W regimen, reductions ranging from 20% to 38% in magnitude. With
      respect to unbrushed surfaces, there was a significant difference between the B
      CPC regimen and the B-60 min.-CPC regimen (p < 0.01) in favour of the latter
      regimen. No other pairwise treatment comparisons were statistically significant
      for unbrushed sites. Results for brushed surfaces and all sites combined showed
      that both the B-W-CPC and the B-60 min.-CPC groups reduced mean plaque levels
      significantly (p < or = 0.013) more than B-CPC. There were no statistically
      significant differences between B-W-CPC and B-60 min.-CPC for measurements of
      brushed, unbrushed, or all sites combined. CONCLUSIONS: Results show that the
      alcohol-free, 0.07% high bioavailable CPC rinse provides an additive anti-plaque
      benefit beyond toothbrushing with a standard fluoride dentifrice regardless of
      the regimen. Of the regimens, a water rinse between toothbrushing and CPC rinsing
      enhances therapeutic efficacy while fitting into the patient's typical oral
      hygiene routine.

PMID- 16899027
TI  - Tooth loss in well-maintained patients with chronic periodontitis during long
      term supportive therapy in Brazil.
AB  - AIM: The objective of this retrospective study was to assess the reasons for
      tooth loss in a sample of patients who underwent periodontal therapy and
      supportive periodontal therapy (SPT) in a Brazilian private periodontal practice.
      MATERIAL AND METHODS: A sample of 120 subjects who had been treated and
      maintained for 10 years or longer was selected from patients attending a
      periodontal practice. All patients followed a similar treatment: basic
      procedures, re-evaluation and periodontal surgery where indicated. Reasons for
      tooth loss were categorized as periodontal, caries, endodontal, root fractures
      and extraction of retained or partially erupted third molars. RESULTS: Of the
      2927 teeth present at the completion of active periodontal treatment, 53 (1.8%)
      were lost due to periodontal disease, 16 (0.5%) for root fracture, six (0.2%) to
      caries, five (0.2%) for endodontic reasons and 31 (1.0%) were lost to extraction
      of retained or partially erupted third molars. Logistic regression analysis was
      performed to investigate the association between five independent variables with
      tooth loss due to periodontitis. Only age (> 60 years) and smoking were
      statistically significant (p < 0.05). CONCLUSION: The findings of this survey
      were consistent with previous studies. Older subjects and smokers were more
      susceptible to periodontal tooth loss. In addition, patients with generalized
      chronic periodontitis were treated and maintained for long-term periods with low
      rates of tooth loss.

PMID- 16899028
TI  - Stromal-derived factor-1 abolishes constitutive apoptosis of WHIM syndrome
      neutrophils harbouring a truncating CXCR4 mutation.
AB  - Warts, hypogammaglobulinaemia, infections, myelokathexis (WHIM) syndrome is an
      inherited immune disorder associated with CXCR4 gene mutations. Recent studies
      suggested that impaired receptor downregulation and enhanced chemotactic
      responsiveness to stromal-derived factor-1 (SDF-1), the sole cognate ligand for
      CXCR4, may account for the characteristic features of WHIM patients. This study
      evaluated whether the interaction of SDF-1 with CXCR4 could block constitutive
      apoptosis of peripheral blood neutrophils from congenital neutropenia patients
      and controls. SDF-1 was found to be a potent anti-apoptotic factor for WHIM
      neutrophils harbouring a truncating CXCR4 mutation, but not for neutrophils from
      control individuals, thus supporting the notion that such mutations may confer
      enhanced functional responses.

PMID- 16899029
TI  - Reducing adverse outcomes from prenatal alcohol exposure: a clinical plan of
      action.
AB  - Fetal alcohol spectrum disorders (FASDs) are among the leading preventable causes
      of developmental disorders in the United States; however, recognition and
      prevention of these conditions cannot be achieved without informed and educated
      health providers. This commentary addresses the importance of recognition and
      prevention of FASDs through the use of well-established standardized practices of
      diagnosis, screening, and brief alcohol reduction counseling. It is hoped that
      more knowledge on currently available procedures will encourage their use in the
      provision of routine health care to all women of childbearing age.

PMID- 16899030
TI  - Standardization of alcohol calculations in research.
AB  - BACKGROUND: Nonstandardized reporting of alcohol consumption, definitions of what
      constitutes a standard drink, and incomplete dosing or estimates of intoxication
      are common problems in many areas of alcohol research. To enhance communication
      among scientists and to make interpretation of results more accurate and
      meaningful, researchers need to apply systematically current scientific
      principles in calculating drinks, doses, and alcohol concentrations. Basic
      formulas are compiled and explained to assist alcohol researchers and standardize
      the reporting and interpretation of alcohol data. METHODS: Basic alcohol
      calculations are reviewed, and 20 mathematical calculations in alcohol
      pharmacokinetics and pharmacology are derived. Examples of how each calculation
      works are presented. RESULTS: The formulas presented enable researchers to
      calculate accurately and systematically the amount of alcohol in any beverage and
      estimate the blood alcohol concentration in a range of subjects with individual
      characteristics and drinking patterns. CONCLUSIONS: Accurate estimates of alcohol
      use and intoxication are important in many areas of research. Applying standards
      to the way alcohol is measured and interpreted enables better communication, more
      accurate analyses, and, in some cases, may impact the interpretation of results.
      Regardless of the field of study, alcohol researchers are encouraged to and can
      apply uniform standards in measuring alcohol consumption and estimating the
      effects of alcohol using the scientific methodologies described.

PMID- 16899031
TI  - Genetic moderators of naltrexone's effects on alcohol cue reactivity.
AB  - BACKGROUND: Naltrexone (NTX) reduces drinking and craving in alcoholic
      individuals in treatment and also in heavy drinkers. Polymorphisms in the D4
      dopamine receptor (DRD4) gene and mu-opiate receptor gene (OPRM1) may moderate
      NTX's effects on craving. This study examined these candidate genes as moderators
      of the effects of NTX on cue-elicited urge to drink in non-treatment-seeking
      heavy drinkers. METHOD: Data from the subset of 93 participants who consented for
      genetic testing in a larger study of medication effects were used to examine
      pharmacogenetic hypotheses. The non-treatment-seeking male and female heavy
      drinkers (62% alcohol dependent) were genotyped for the variable number of tandem
      repeats polymorphism in the DRD4 gene [L=7 or more (n=34), S=less than 7 (n=56)]
      and Asn40Asp single-nucleotide polymorphism in the OPRM1 gene [29 aspartate (Asp)
      carriers and 59 asparagine (Asn) homozygotes]. Ten days after randomization to
      NTX (50 mg) or placebo, participants completed an alcohol cue reactivity
      assessment. RESULTS: Any medication effects were all accounted for by interaction
      with genotype. Naltrexone increased urge for alcohol in Asp carriers across
      alcohol and neutral beverage cue trials and had no effect on homozygous Asn
      carriers. Asp40 carriers on either medication had greater decreases (from resting
      baseline) in mean arterial blood pressure across all beverage cue trials compared
      with Asn carriers. For DRD4, no differential medication effects by DRD4
      polymorphism were found. Alcohol dependence diagnosis did not moderate the
      effects of gene and medication on cue-elicited measures. DISCUSSION: The
      differential responses to NTX due to variation in the OPRM1 gene may help explain
      conflicting results in clinical trials and suggest directions for patient
      treatment matching.

PMID- 16899032
TI  - Alcohol and indinavir adversely affect protein synthesis and phosphorylation of
      MAPK and mTOR signaling pathways in C2C12 myocytes.
AB  - BACKGROUND: Alcohol and the antiretroviral drug indinavir (Ind) decrease protein
      synthesis in skeletal muscle under in vivo and in vitro conditions. The goal of
      the present study was to identify signaling mechanisms responsible for the
      inhibitory effect of ethanol (EtOH) and Ind on protein synthesis. METHODS: C2C12
      mouse myocytes were incubated with EtOH, Ind, or a combination of both for 24
      hours. The rate of protein synthesis was determined by [35S]methionine/cysteine
      incorporation into cellular protein. Phosphorylation of eukaryotic initiation and
      elongation factors were quantitated by Western blot analysis to identify
      potential mechanisms for regulating translation. RESULTS: Treatment of myocytes
      with Ind or EtOH for 24 hours decreased protein synthesis by 19 and 22%,
      respectively, while a 35% decline was observed in cells treated simultaneously
      with both agents. Mechanistically, treatment with EtOH or Ind decreased the
      phosphorylation of the S6 ribosomal protein, and this reduction was associated
      with decreased S6K1 and p90rsk phosphorylation. Ethanol also decreased the
      phosphorylation of ERK1/2, mTOR, and 4EBP1, while Ind only suppressed ERK1/2
      phosphorylation. Both agents inhibited the phosphorylation of Mnk1 and its
      upstream regulator p38 MAPK, and they decreased the amount of the active
      eukaryotic initiation factor (eIF) 4G/eIF4E complex. Finally, EtOH and/or Ind
      increased phosphorylation of the eukaryotic elongation factor (eEF)-2 by 1.6- to
      6-fold. The effects of these agents were not additive, although the combination
      did exert a greater effect on S6K1 and eEF2 phosphorylation. CONCLUSIONS: Ethanol
      and Ind decreased protein synthesis in myocytes and this response was associated
      with changes in the phosphorylation of proteins that regulate translation
      initiation and elongation.

PMID- 16899033
TI  - Relationships among the level of response to alcohol and the number of alcoholic
      relatives in predicting alcohol-related outcomes.
AB  - BACKGROUND: The low level of response (LR) to alcohol is related to a family
      history (FH) of alcohol use disorders (AUDs), and each predicts alcohol-related
      outcomes. Few studies have evaluated the interrelationships between the number of
      alcoholic relatives, LR, and a range of alcohol-related outcomes. This study
      tests the hypotheses that there will be an inverse relationship between LR and FH
      and that LR will be a better predictor of the maximum quantity of alcohol
      consumed. METHODS: Data were extracted from personal interviews with 376 males
      from 20 years of follow-up in the San Diego Prospective Study. Level of response
      had been established at about age 20 through alcohol challenges in this
      population, about half of whom had at least one alcoholic relative. Face-to-face
      follow-ups with both the subjects and additional informants were carried out 10,
      15, and 20 years later. These analyses used correlations and regressions to
      evaluate the relationship between the 2 major predictors (FH and LR) and 5
      alcohol-related outcomes over 20 years of follow-up. RESULTS: As predicted, the
      alcohol challenge-based LR correlated significantly with the number of alcoholic
      relatives (up to -0.17 for subjects with clearly high and low LR scores). Each of
      the 2 predictors correlated with the 5 outcomes, including the maximum quantity
      of alcohol consumed since original testing, maximum frequency, nondiagnostic
      alcohol-related problems, the number of 11 DSM-IV (Fourth Diagnostic and
      Statistical Manual of Mental Disorders) abuse and dependence items, and having
      developed alcohol abuse or dependence. In hierarchical regression analyses, LR
      contributed significantly to the prediction of all 5 outcomes, even when
      considered in the context of FH, with only LR predicting drinking quantity and
      frequency, but both items adding to the prediction of alcohol-related problems
      and diagnoses. These results were not affected by the intensity of usual drinking
      when LR had been measured at age 20. CONCLUSIONS: Both FH and LR contributed to a
      range of alcohol-related outcomes, with LR alone significantly predicting maximum
      quantity and frequency in regression analyses.

PMID- 16899034
TI  - Factor structure of the alcohol urge questionnaire under neutral conditions and
      during a cue-elicited urge state.
AB  - BACKGROUND: The Alcohol Urge Questionnaire (AUQ) is a promising multi-item
      measure of self-reported urges to drink in human laboratory studies; however, its
      factor structure has not been examined during an acute urge state. This study
      sought to validate the AUQ's factor structure under neutral conditions and during
      a cue-elicited urge state in heavy drinkers. METHODS: Participants (248 heavy
      drinkers; 70% male) completed the AUQ, the Alcohol Dependence Scale (ADS), and
      the Positive and Negative Affect Scale (PANAS) under neutral conditions. A
      randomly selected subsample (n=61; 74% male) then underwent a multimodal alcohol
      cue exposure and completed the AUQ and PANAS a second time. RESULTS: Under
      neutral conditions, confirmatory factor analysis (CFA) replicated the previously
      reported single-factor structure, on which all items significantly loaded
      (p<0.001). Alcohol urges, as measured by the AUQ, exhibited significant positive
      associations with drinks per week and severity of dependence. Following the
      alcohol cue exposure, participants exhibited a significant increase in urge on
      the AUQ. Confirmatory factor analysis of the AUQ during the cue-elicited urge
      state also supported the single factor structure, on which all items
      significantly loaded (p<0.001). Positive and negative affect were positively
      associated with urges across the experimental protocol, but at greater magnitudes
      during an acutely elevated urge state. CONCLUSIONS: These results further
      validate the use of the AUQ for real-time measurement of alcohol craving in human
      laboratory research.

PMID- 16899035
TI  - Neuroadaptations of Cdk5 in cholinergic interneurons of the nucleus accumbens and
      prefrontal cortex of inbred alcohol-preferring rats following voluntary alcohol
      drinking.
AB  - BACKGROUND: Neurobiological studies have identified brain areas and related
      molecular mechanisms involved in alcohol abuse and dependence. Specific cell
      types in these brain areas and their role in alcohol-related behaviors, however,
      have not yet been identified. This study examined the involvement of cholinergic
      cells in inbred alcohol-preferring rats following 1 month of alcohol drinking.
      Cyclin-dependent kinase 5 (Cdk5) immunoreactivity (IR), a marker of neuronal
      plasticity, was examined in cholinergic neurons of the nucleus accumbens (NuAcc)
      and prefrontal cortex (PFC) and other brain areas implicated in alcohol drinking,
      using dual immunocytochemical (ICC) procedures. Single Cdk5 IR was also examined
      in several brain areas implicated in alcohol drinking. METHODS: The experimental
      group self-administered alcohol using a 2-bottle-choice test paradigm with
      unlimited access to 10% (v/v) alcohol and water for 23 h/d for 1 month. An
      average of 6 g/kg alcohol was consumed daily. Control animals received identical
      treatment, except that both bottles contained water. Rats were perfused and brain
      sections were processed for ICC procedures. RESULTS: Alcohol drinking resulted in
      a 51% increase in Cdk5 IR cholinergic interneurons in the shell NuAcc, while in
      the PFC there was a 51% decrease in the percent of Cdk5 IR cholinergic
      interneurons in the infralimbic region and a 46% decrease in Cdk5 IR cholinergic
      interneurons in the prelimbic region. Additionally, single Cdk5 IR revealed a 42%
      increase in the central nucleus of the amygdala (CNA). CONCLUSIONS: This study
      identified Cdk5 neuroadaptation in cholinergic interneurons of the NuAcc and PFC
      and in other neurons of the CNA following 1 month of alcohol drinking. These
      findings contribute to our understanding of the cellular and molecular basis of
      alcohol drinking and toward the development of improved region and cell-specific
      pharmacotherapeutic and behavioral treatment programs for alcohol abuse and
      alcoholism.

PMID- 16899037
TI  - Blockade of cue-induced brain activation of abstinent alcoholics by a single
      administration of amisulpride as measured with fMRI.
AB  - BACKGROUND: Once alcohol dependence is established, alcohol-associated cues may
      induce dopamine release in the reward system, which is accompanied by alcohol
      craving and may lead to relapse. In cocaine addicts, dopamine release in the
      thalamus was positively correlated with cocaine craving. We tested the effects of
      the atypical dopamine D(2/3) blocker amisulpride on cue-induced brain activation
      in a functional magnetic resonance imaging (fMRI) paradigm. METHODS: Alcohol
      associated and neutral pictures were presented in a block design to 10 male
      abstinent alcoholics (1-3 weeks after detoxification) and 10 healthy men during
      fMRI. The fMRI scans were acquired before and 2 hours after the oral application
      of 400 mg amisulpride. Before and after each scan, alcohol craving was measured
      with visual analogue scales. RESULTS: Before the application of amisulpride,
      alcohol versus control cues elicited a higher blood oxygen level-dependent (BOLD)
      signal in the left frontal and orbitofrontal lobe, left cingulate gyrus,
      bilateral parietal lobe, and bilateral hippocampus in alcoholics compared with
      healthy controls. After amisulpride, alcoholics showed a reduced activation in
      the right thalamus compared with the first scan. Alcoholics no longer showed
      significant differences in their cue-elicited BOLD response after amisulpride
      medication compared with medication-free controls. Self-reported craving was not
      affected by amisulpride medication. CONCLUSIONS: Amisulpride medication was
      associated with reduced cue-induced activation of the thalamus, a brain region
      closely connected with frontostriatal circuits that regulate behavior and may
      influence relapse risk.

PMID- 16899036
TI  - Is the strength of implicit alcohol associations correlated with alcohol-induced
      heart-rate acceleration?
AB  - BACKGROUND: Heart rate (HR) acceleration during the ascending limb of the blood
      alcohol curve has proven to be a reliable measure of the sensitivity to the
      activating effects of alcohol. In this study, we investigated the correlation
      between an ethanol-induced cardiac change and the strength of implicit alcohol
      related arousal and approach associations and attentional bias for alcohol
      related stimuli in heavy drinkers. These 3 types of implicit alcohol-related
      cognitions have been proposed to reflect the strength of incentive sensitization
      that is experienced after repeated alcohol use. METHODS: Forty-eight heavy
      drinking men performed a modified version of the Implicit Association Test (IAT)
      to measure their implicit alcohol arousal and approach-avoidance associations. A
      modified version of the emotional Stroop was used to measure attentional bias for
      alcohol-related stimuli (blocked and unblocked). Next, a high dose of alcohol
      (1.0 mL/kg body weight 95% USP alcohol) was administered in a short period of
      time. Resting baseline HR, blood alcohol concentrations, mood, and craving for
      alcohol were assessed before alcohol administration and for 2 hours post-alcohol
      consumption. RESULTS: Contrary to our hypothesis, a negative association was
      found between implicit arousal associations and alcohol-induced HR change. This
      indicates that strong arousal associations were correlated with a decrease in
      alcohol-induced HR. Approach associations and attentional bias were not
      correlated with alcohol-induced HR change, but both were correlated positively
      with each other. CONCLUSIONS: Alcohol-arousal associations and other implicit
      cognitions (attentional bias, approach associations) are not positively related
      to individual differences in the sensitivity to alcohol's activating effects, at
      least not in the present sample consisting primarily of family history-negative
      heavy drinkers.

PMID- 16899038
TI  - Executive function and memory in relation to olfactory deficits in alcohol
      dependent patients.
AB  - BACKGROUND: Prior research indicates that chronic alcoholism is accompanied by
      olfactory deficits. These have been suggested to reflect dysfunctions in
      olfactory brain regions. The present study investigated the role of
      neurocognitive functioning in tests (executive function and memory) sensitive to
      the functional integrity of brain areas that are crucial to olfactory processing
      in patients with alcohol dependence. METHODS: Performance on olfactory functions
      (detection threshold, quality discrimination, identification), executive function
      (Wisconsin Card Sorting Test), and memory (German version of the California
      Verbal Learning Test) was assessed in 32 alcohol-dependent patients and 30
      healthy comparison subjects, comparable in age, gender, and smoking status.
      RESULTS: Compared with controls, alcohol-dependent patients were impaired in all
      3 domains, olfactory functions, executive function, and memory. In patients,
      olfactory discrimination ability was positively correlated with executive
      function performance. Regression analyses conducted to clarify the relation
      between group (patients vs controls), executive function, memory, and olfactory
      functions indicated that group was the only significant predictor of olfactory
      detection threshold and identification, and both group and executive function
      were found to be the significant predictors of olfactory discrimination.
      CONCLUSIONS: Olfactory deficits in alcohol dependence appear to be associated
      with prefrontal cognitive dysfunction. Results indicate that olfactory quality
      discrimination deficits are related to executive function impairment. These
      findings add to the available research on frontal lobe dysfunction in alcoholism,
      suggesting that alcohol-related olfactory discrimination deficits may be
      associated with impairment in the functional integrity of the prefrontal lobe.

PMID- 16899039
TI  - Alcohol attenuates load-related activation during a working memory task: relation
      to level of response to alcohol.
AB  - BACKGROUND: A low level of response to alcohol is a major risk factor for the
      development of alcohol dependence, but neural correlates of this marker are
      unclear. METHOD: Ten healthy volunteers were classified by median split on level
      of response to alcohol and underwent 2 sessions of functional magnetic resonance
      imaging following ingestion of a moderate dose of alcohol and a placebo. The
      blood oxygen level-dependent activation to an event-related visual working memory
      test was examined. RESULTS: The subjects exhibited longer response latencies and
      more errors as a function of increasing working memory load and showed a load
      dependent increase in activation in dorsolateral prefrontal cortex, posterior
      parietal cortex, and visual cortex. Alcohol did not affect performance (errors or
      response latency), but attenuated the working memory load-dependent activation in
      the dorsolateral prefrontal cortex. During the placebo condition, individuals
      with a low level of response to alcohol showed greater activation in dorsolateral
      prefrontal cortex and posterior parietal cortex than those with a high level of
      response to alcohol. During the alcohol condition, groups showed similar
      attenuation of load-dependent brain activation in these regions. CONCLUSION: Low
      level responders relative to high-level responders exhibited an increased working
      memory load-dependent activation in dorsolateral prefrontal cortex and posterior
      parietal cortex when not exposed to alcohol. This increase in brain response was
      attenuated in low-level responders after ingesting a moderate dose of alcohol.

PMID- 16899040
TI  - DOVER and QUVER-new marker combinations to detect and monitor at-risk drinking.
AB  - BACKGROUND: At-risk drinking is a common medical problem. "Objective" laboratory
      tests are widely used, especially in situations where it might be favorable for
      the patient to dissimulate the existing alcohol problem. In this study, we report
      a new approach to combine the biological markers % carbohydrate-deficient
      transferrin (%CDT) and gamma-glutamyltransferase (gammaGT) to increase diagnostic
      properties to identify patients with at-risk drinking behavior. METHODS: Fifty
      eight general practitioners (GPs) participated in the study at 2 study sites in
      South-West Germany. Patients filled in a questionnaire that included the Alcohol
      Use Disorders Identification Test (AUDIT) and gave a blood sample. The GP
      recorded his assessment about the presence of an alcohol-related disorder in the
      patient. Screening results of 1 test center were used as a calculation sample.
      The results at the other site were used to cross-validate the study outcomes. The
      markers were combined by 2 methods. The first approach used the AUDIT
      (QUestionnaire VERified; QUVER), and the second was performed using the clinical
      judgment of the treating GP (DOctor VERified; DOVER). The formulas were
      calculated using linear and logistic regression models, respectively. RESULTS: A
      total of 2,940 patients participated in the study, of whom 2,496 completed data
      sets that could be used for further analysis. In the receiver-operating
      characteristics (ROC) curves with the reference standard of an AUDIT> or =8, the
      area under the curve (AUC) of 78.8% for DOVER and 80.6% (QUVER) are in a higher
      range than the values for gamma-%CDT (75.4%) or gamma-GT (66.3%) and %CDT (74.3%)
      and suggest a clear superiority of the proposed marker combinations. Regarding
      the combinations DOVER and QUVER, the cross-validation results were almost
      identical, with 78.4/78.8% and 80.6/79.5%, respectively. CONCLUSION: Our study is
      to date the largest practice-based trial that examines the value of the markers
      CDT and gamma-GT and their combinations for the screening of at-risk drinking in
      general practice under routine conditions. Our ROC analysis clearly demonstrated
      that the combination of the markers gamma-GT and %CDT under routine conditions
      with a behaviorally oriented reference standard leads to an improvement of
      diagnostic performance, more so than the use of single markers.

PMID- 16899041
TI  - A 3-year study of addiction mutual-help group participation following intensive
      outpatient treatment.
AB  - BACKGROUND: Addiction-focused mutual-help group participation is associated with
      better substance use disorder (SUD) treatment outcomes. However, little has been
      documented regarding which types of mutual-help organizations patients attend,
      what levels of participation may be beneficial, and which patients, in
      particular, are more or less likely to participate. Furthermore, much of the
      evidence supporting the use of these organizations comes from studies examining
      participation and outcomes concurrently, raising doubts about cause-effect
      connections, and little is known about influences that may moderate the degree of
      any general benefit. METHOD: Alcohol-dependent outpatients (N=227; 27% female; M
      age=42) enrolled in a randomized-controlled telephone case monitoring trial were
      assessed at treatment intake and at 1, 2, and 3 years postdischarge. Lagged
      panel, hierarchical linear models tested whether mutual-help group participation
      in the first and second year following treatment predicted subsequent outcomes
      and whether these effects were moderated by gender, concurrent axis I diagnosis,
      religious preference, and prior mutual-help experience. Robust regression curve
      analysis was used to examine dose-response relationships between mutual-help and
      outcomes. RESULTS: Mutual-help participation was associated with both greater
      abstinence and fewer drinks per drinking day and this relationship was not found
      to be influenced by gender, Axis I diagnosis, religious preference, or prior
      mutual-help participation. Mutual-help participants attended predominantly
      Alcoholics Anonymous and tended to be Caucasian, be more educated, have prior
      mutual-help experience, and have more severe alcohol involvement. Dose-response
      curve analyses suggested that even small amounts of participation may be helpful
      in increasing abstinence, whereas higher doses may be needed to reduce relapse
      intensity. CONCLUSIONS: Use of mutual-help groups following intensive outpatient
      SUD treatment appears to be beneficial for many different types of patients and
      even modest levels of participation may be helpful. Future emphasis should be
      placed on ways to engage individuals with these cost-effective resources over
      time and to gather and disseminate evidence regarding additional mutual-help
      organizations.

PMID- 16899042
TI  - An interdisciplinary faculty development model for the prevention and treatment
      of alcohol use disorders.
AB  - BACKGROUND: The skills of faculty working in health fields are inadequate to meet
      the needs of those adversely affected by alcohol. This project was designed to
      increase the teaching, clinical, and research activities of faculty from multiple
      disciplines at the university level. METHODS: The faculty development model
      included two 2-day skills-based courses held 6 months apart, precourse and
      postcourse evaluations, active mentoring, and development of a specific work plan
      for each participant. The educational model utilized skills-based courses
      previously developed for full-time clinical/teaching medical faculty with limited
      time and resources. RESULTS: A total of 153 participants at 6 locations completed
      the courses; 131 completed the 6-month follow-up interview. Sixty-four designed
      teaching, clinical, or research projects during the 6-month period between the
      first and second courses. Precourse versus postcourse clinical scores from
      standardized patient encounters showed highly significant improvements in
      screening, brief intervention, and motivational interviewing skills (p<0.001). At
      the 6-month follow-up interview, 61% of the participants reported teaching on
      alcohol, tobacco, or drug problems; 49% reported clinical activities in this
      area; 36% reported conducting research; 10% had submitted manuscripts for
      publication; 12% had submitted grant applications; and 32% percent had sought
      additional AODA training. Participants gave high scores to all components of the
      faculty development model; 81% would repeat the training and 98% would recommend
      the program to colleagues. CONCLUSIONS: This cost-effective faculty development
      program can serve as a model to increase educational programs on substance abuse
      at public universities, increase faculty research activities in the alcohol area,
      and increase clinical programs in university hospitals.

PMID- 16899043
TI  - Competing presynaptic and postsynaptic effects of ethanol on cerebellar purkinje
      neurons.
AB  - BACKGROUND: Ethanol has actions on cerebellar Purkinje neurons that can result
      either in a net excitation or in inhibition of neuronal activity. The present
      study examines the interplay of presynaptic and postsynaptic mechanisms to
      determine the net effect of ethanol on the neuronal firing rate of cerebellar
      Purkinje neurons. METHODS: Whole-cell voltage-clamp recording of miniature
      inhibitory postsynaptic currents (mIPSCs) from Purkinje neurons in cerebellar
      slices was used to examine the effect of ethanol on presynapticsynaptic release
      of gamma-aminobutyric acid (GABA) and glutamate. Extracellular recording was used
      to examine the net action of both presynaptic and postsynaptic effects of ethanol
      on the firing rate of Purkinje neurons. RESULTS: Under whole-cell voltage clamp,
      the frequency of bicuculline-sensitive miniature postsynaptic currents (mIPSCs)
      was increased dose-dependently by 25, 50, and 100 mM ethanol without any change
      in amplitude or decay time. Despite this evidence of increased release of GABA by
      ethanol, application of 50 mM ethanol caused an increase in firing in some
      neurons and a decrease in firing in others with a nonrandom distribution. When
      both glutamatergic and GABAergic influences were removed by simultaneous
      application of 6-cyano-7-nitroquinoxaline-2,3-dione and picrotoxin, respectively,
      ethanol caused only an increase in firing rate. CONCLUSIONS: These data are
      consistent with a dual action of ethanol on cerebellar Purkinje neuron activity.
      Specifically, ethanol acts presynaptically to increase inhibition by release of
      GABA, while simultaneously acting postsynaptically to increase intrinsic
      excitatory drive.

PMID- 16899045
TI  - Nicotine stimulation on extracellular glutamate levels in the nucleus accumbens
      of ethanol-withdrawn rats in vivo.
AB  - BACKGROUND: Nicotine can release glutamate in the limbic system. Presynaptic
      activation of glutamate receptors might be relevant for the subsequent firing of
      excitatory postsynaptic potentials. This might be relevant in early ethanol
      withdrawal. The effects and differences of nicotine stimulation on glutamate
      response measured by microdialysis in the nucleus accumbens (NAC) between ethanol
      withdrawn rats (EW group) and ethanol-naive rats (control group) were
      investigated. METHODS: Rats were ethanol-intoxicated according to a binge
      drinking model: recurrent cycle of 4 days of intoxication (EW group) or 5%
      sucrose (control group), followed by a 3-day recovery. This was followed by a 2
      day intoxication period and subsequent abstinence. After the last oral intake,
      microdialysis was performed in the left NAC for a 16-hour withdrawal period. At
      the end of the withdrawal period, a rated withdrawal score (RWS) was documented.
      Then, nicotine was given subcutaneously at a dose of 0.5 mg/kg and amino acid
      levels determined by microdialysis were followed for an additional 3 hours.
      RESULTS: The RWS was not correlated to the last amount of ethanol received, but
      was correlated to the total amount of ethanol administered during the
      pretreatment period: the basal values of extracellular glutamate were found to be
      decreased in the EW group before withdrawal. Cessation of ethanol significantly
      increased glutamate levels with a peak between 4 and 10 hours after the last oral
      intake. Sixteen hours after ethanol withdrawal, the same level as in the control
      group was achieved. Nicotine significantly increased glutamate levels in the NAC
      of the EW group but not in ethanol-naive rats. CONCLUSIONS: This study showed
      that withdrawal of ethanol was associated with an increase in extracellular
      glutamate levels. Systemic administration of nicotine in vivo produced an
      increase in extracellular levels of glutamate in the core region of the NAC
      during ethanol withdrawal. This might be a relevant pathomechanism for increased
      craving either for alcohol or for nicotine after ethanol withdrawal.

PMID- 16899046
TI  - Serum leptin in patients with alcoholic liver disease.
AB  - BACKGROUND: The mechanisms by which overweight makes the liver more susceptible
      to alcoholic liver injury remain to be determined. Therefore, we conducted the
      following studies to further elucidate the role of leptin in the pathogenesis of
      steatosis and cirrhosis caused by chronic alcohol consumption in human beings.
      METHODS: Two-hundred nine consecutive patients with alcoholic liver disease were
      studied. Serum leptin concentrations were measured by using radioimmunoassay, and
      the relationships between serum leptin level and liver lesions were studied.
      Statistical analysis used logistic regressions. RESULTS: When serum leptin, serum
      cholesterol, and body mass index (BMI) were considered together in the multiple
      logistic regression analysis, compared with patients with severe steatosis, serum
      leptin remains significantly lower in patients without steatosis (p<0.05) and in
      patients with mild or moderate steatosis (p<0.05). When age, serum leptin, serum
      cholesterol, and steatosis grade were considered together in the logistic
      regression analysis, serum leptin (p<0.01) and age (p<0.02) were positively and
      independently correlated with the presence of cirrhosis. After BMI introduction
      in the statistical model, serum leptin was no more correlated with the presence
      of cirrhosis. CONCLUSION: In patients with alcoholic liver disease, serum leptin
      is independently correlated with steatosis grade and might play an important role
      in severity of fibrosis as fatty liver is more vulnerable than normal liver to
      factors that lead to fibrosis.

PMID- 16899044
TI  - Nicotine decreases blood alcohol concentrations in adult rats: a phenomenon
      potentially related to gastric function.
AB  - BACKGROUND: In spite of the fact that drinking and smoking often occur together,
      little is known about the pharmacokinetic interaction between alcohol and
      nicotine. Previous research in neonatal rats demonstrated that nicotine reduces
      blood alcohol concentrations (BACs) if alcohol and nicotine are administered
      simultaneously. However, it is unclear whether such a phenomenon can be observed
      in adult subjects, given the fact that there is an ontogenetic difference in
      alcohol metabolism. METHODS: A range of nicotine doses (0, 0.25, 0.5, 1, 2, 4,
      and 6 mg/kg) were administered individually with an alcohol dose (4 g/kg) via
      intragastric (IG) intubation to adult female rats, and the resultant BACs were
      measured at various time points following drug administration. Furthermore, the
      hypothesis that nicotine's role in reducing BACs is mediated through factors
      related to gastric function was examined by comparing the resultant BACs after an
      IG intubation or intraperitoneal (IP) injection of alcohol. RESULTS: The results
      from this study showed significant nicotine dose-related decreases in BACs with
      0.5, 1, 2, 4, and 6 mg/kg doses of nicotine at the various time points assessed.
      This effect, however, occurred only when alcohol was administered via IG
      intubation, but not after an IP injection of alcohol. CONCLUSIONS: These results
      suggest that the nicotine-induced decrease in BAC may be related to gastric
      function. One possible explanation was related to nicotine's action in delaying
      gastric emptying. The longer the alcohol was retained in the stomach, the more
      likely that the alcohol would be metabolized by gastric alcohol dehydrogenase
      before its absorption into the bloodstream by the small intestine (the major site
      of alcohol absorption).

PMID- 16899048
TI  - Ethanol suppresses LPS-induced Toll-like receptor 4 clustering, reorganization of
      the actin cytoskeleton, and associated TNF-alpha production.
AB  - BACKGROUND: Ethanol (EtOH) suppresses cytokine responses induced through most
      Toll-like receptors (TLRs), but the mechanism of action is unclear. We recently
      found that acute EtOH alters lipopolysaccharide (LPS)-induced partitioning of
      CD14, a critical component of the LPS receptor complex, within lipid raft
      fractions in the macrophage-like cell line RAW264.7. METHODS: Here we
      investigated the role of receptor clustering in alteration of the responses of
      cells to LPS caused by EtOH both in vitro and in vivo. The cellular distribution
      of CD14, TLR4, actin cytoskeleton, and tumor necrosis factor-alpha (TNF-alpha)
      were studied by confocal microscopy following exposure of cells to LPS with or
      without EtOH. TLR4 and CD14 were clustered into highly colocalized patches on the
      cell membrane accompanied by the reorganization of the actin cytoskeleton in some
      of the RAW264.7 cells as well as peritoneal cells following LPS treatment.
      RESULTS: Addition of EtOH reduced the number of cells that had LPS-induced
      receptor patches and in which this reorganization occurred. Cells on which CD14
      and TLR4 formed clusters or caps had substantially higher levels of membrane
      bound TNF-alpha compared with cells without clustering or capping of these
      molecules. Interference with the actin cytoskeleton by cytochalasin D suppressed
      the production of TNF-alpha and receptor clustering, as EtOH did. CONCLUSIONS:
      These data confirm our previous observations, suggest a novel mechanism of EtOH
      action that involves interference with receptor clustering, and indicate a
      potential role of actin filaments in the formation of receptor patches,
      subsequent activation of macrophages by LPS, and production of TNF-alpha.

PMID- 16899047
TI  - Effects of ethanol and acetaldehyde on reactive oxygen species production in rat
      hepatic stellate cells.
AB  - BACKGROUND: Alcoholism is a common cause of cirrhosis. Hepatic stellate cells are
      the main source of collagen that ultimately leads to hepatic fibrosis and
      cirrhosis. Reactive oxygen species (ROS) enhance stellate cell activation and
      stimulate fibrogenesis. In this study, the acute effects of ethanol (ET) and
      acetaldehyde (AC) were determined on the production of ROS in isolated rat
      hepatic stellate cells. METHODS: Rat stellate cells were isolated in situ by
      perfusion of the portal vein and cultured. Hydrogen peroxide (H(2)O(2)) was
      determined by luminol-derived chemiluminescence (CL), while superoxide anion
      (O(2*-)) production was assessed by the fluorescent probe hydroethidine. RESULTS:
      AC increased the formation of H(2)O(2) and O(2*-), and these effects were first
      detectable at AC concentrations of 5 and 10 microM, respectively, reaching a
      maximum at 50 to 75 microM. Reduction of glutathione (GSH) synthesis by 1
      buthionine sulfoximide (BSO) or by GSH conjugation with dimethylmaleate (DEM)
      further enhanced the effects of AC on H(2)O(2) and O(2*-) formation, while N
      acetylcysteine (NAC) decreased H(2)O(2) and eliminated the enhanced generation of
      O(2*-) caused by AC. Raloxifene, which inhibits O(2*-) production by NAD(P)H
      oxidase, reduced the effects of AC on H(2)O(2) and O(2*-) production. ET
      increased H(2)O(2) or O(2*-) only in the presence of BSO or DEM. CONCLUSION: This
      study shows that concentrations of AC, which occur in vivo after the ingestion of
      alcoholic beverages, result in the formation of ROS in rat hepatic stellate
      cells. The increases in ROS are known to activate stellate cells promoting
      fibrogenesis.

PMID- 16899050
TI  - Single amino acid residue changes in subsite -1 of inulosucrase from
      Lactobacillus reuteri 121 strongly influence the size of products synthesized.
AB  - Bacterial fructansucrase enzymes belong to glycoside hydrolase family 68 and
      catalyze transglycosylation reactions with sucrose, resulting in the synthesis of
      fructooligosaccharides and/or a fructan polymer. Significant differences in
      fructansucrase enzyme product specificities can be observed, i.e. in the type of
      polymer (levan or inulin) synthesized, and in the ratio of polymer versus
      fructooligosaccharide synthesis. The Lactobacillus reuteri 121 inulosucrase
      enzyme produces a diverse range of fructooligosaccharide molecules and a minor
      amount of inulin polymer [with beta(2-1) linkages]. The three-dimensional
      structure of levansucrase (SacB) of Bacillus subtilis revealed eight amino acid
      residues interacting with sucrose. Sequence alignments showed that six of these
      eight amino acid residues, including the catalytic triad (D272, E523 and D424,
      inulosucrase numbering), are completely conserved in glycoside hydrolase family
      68. The other three completely conserved residues are located at the -1 subsite
      (W271, W340 and R423). Our aim was to investigate the roles of these conserved
      amino acid residues in inulosucrase mutant proteins with regard to activity and
      product profile. Inulosucrase mutants W340N and R423H were virtually inactive,
      confirming the essential role of these residues in the inulosucrase active site.
      Inulosucrase mutants R423K and W271N were less strongly affected in activity, and
      displayed an altered fructooligosaccharide product pattern from sucrose,
      synthesizing a much lower amount of oligosaccharide and significantly more
      polymer. Our data show that the -1 subsite is not only important for substrate
      recognition and catalysis, but also plays an important role in determining the
      size of the products synthesized.

PMID- 16899049
TI  - Signaling pathways regulating cell motility: a role in ethanol teratogenicity?
AB  - This article summarizes the proceedings of a symposium presented at the 2005
      annual meeting of the Research Society on Alcoholism in Santa Barbara,
      California. The organizer and chair was Tara A. Lindsley. The presentations were
      (1) Ethanol and Neuron Migration in the CNS, by Michael W. Miller; (2) Ethanol
      and L1-mediated Neurite Outgrowth, by Yoav Littner and Cynthia F. Bearer; and (3)
      Ethanol and Axon Guidance, by Tara A. Lindsley.

PMID- 16899051
TI  - Native and subunit molecular mass and quarternary structure of the hemoglobin
      from the primitive branchiopod crustacean Triops cancriformis.
AB  - Many branchiopod crustaceans are endowed with extracellular, high-molecular
      weight hemoglobins whose exact structural characteristics have remained a matter
      of conjecture. By using a broad spectrum of techniques, we provide precise and
      coherent information on the hemoglobin of one of the phylogenetically 'oldest'
      extant branchiopods, the tadpole shrimp Triops cancriformis. The hemoglobin
      dissociated under reducing conditions into two subunits, designated TcHbA and
      TcHbB, with masses of 35,775+/-4 and 36,055+/-4 Da, respectively, determined by
      ESI-MS. Nonreducing conditions showed only two disulfide-bridged dimers, a
      homodimer of TcHbA, designated D1 (71,548+/-5 Da), and the heterodimer D2
      (71,828+/-5 Da). Carbamidomethylation of free SH groups revealed the presence of
      three cysteines per subunit and indicated one intrasubunit and one intersubunit
      disulfide bridge. Ultracentrifugation and light-scattering experiments under
      nondenaturating conditions yielded mass estimates that suggested an uneven number
      of 17 subunits forming the native hemoglobin. This unrealistic number resulted
      from the presence of two size classes (16-mer and 18-mer), which were recognized
      by native PAGE and Ferguson plot analysis. ESI-MS revealed three hemoglobin
      isoforms with masses of 588.1 kDa, 662.0 kDa, and 665.0 kDa. The 16-mer and the
      smaller 18-mer species are supposed to be composed of TcHbA only, given the
      dominance of this subunit type in SDS/PAGE. Transmission electron microscopy of
      negatively stained specimens showed a population of compact molecules with
      geometrical extensions of 14, 16 and 9 nm. The proposed stoichiometric model of
      quarternary structure provides the missing link to achieve a mechanistic
      understanding of the structure-function relationships among the multimeric
      arthropodan hemoglobins.

PMID- 16899052
TI  - Localization of two new X-linked quantitative trait loci controlling corpus
      callosum size in the mouse.
AB  - Corpus callosum (CC) size is a complex trait, characterized by a gradation of
      values within a normal range, as well as abnormalities that include a small or
      totally absent CC. Among inbred mouse strains with defects of the CC, BTBR
      T(+)tf/J (BTBR) mice have the most extreme phenotype; all animals show total
      absence of the CC and severe reduction of the hippocampal commissure (HC). In
      contrast, the BALB/cByJ (BALB) strain has a low frequency of small CC and
      consistently normal HC. Reciprocal F(1) crosses between BTBR and BALB suggest the
      presence of X-linked quantitative trait loci (QTLs) affecting CC size. Through
      linkage analysis of backcross male progeny, we have localized two regions on the
      X chromosome, having peaks at 68.5 Mb (approximately 29.5 cM) and at 134.5 Mb
      (approximately 60.5 cM) that are largely responsible for the reciprocal
      differences, with the BTBR allele showing X-linked dominant inheritance
      associated with CC defects.

PMID- 16899054
TI  - Genetic variation in the hypothalamic-pituitary-adrenocortical axis regulatory
      factor, T-box 19, and the angry/hostility personality trait.
AB  - Neurotic personality traits are important factors in several psychiatric
      disorders and suicidal behavior. Here, we have investigated the existence of
      potential relationships between neurotic personality traits and genetic
      variation. Non-suicidal parents derived from trios (suicide attempter and both
      parents) and non-suicidal volunteers, examined by the Neuroticism, Extraversion
      and Openness (NEO) Personality Inventory - Revised (NEO PI-R), were divided into
      screening and replication samples. The screening sample (n= 127) was used to
      select potential relationships between neurotic personality traits and genetic
      variation among 130 single nucleotide polymorphisms (SNPs). Screening (analysis
      of variance) with regard to the personality dimension neuroticism indicated
      potential relationships at three different loci. More detailed analysis of these
      three SNPs at NEO PI-R facet level indicated four potential relationships. T-test
      analysis in the replication sample (n= 617) was used to retest the relationships
      indicated during screening. One of those relationships was confirmed in the
      replication sample (P= 0.0052; Bonferroni correction), indicating that genetic
      variation at the human T-box 19 (TBX19) locus is related to the personality trait
      angry/hostility. Furthermore, using analysis of haplotypes among trios by
      transmission disequilibrium test and its extension, the family-based association
      test, overtransmission of a haplotype GAC at the TBX19 locus was associated with
      increased angry/hostility scores among suicide attempters (P= 0.009; Bonferroni
      correction). This is to our knowledge the first report on the association of the
      angry hostility personality trait with genetic variation at the TBX19 locus, an
      important regulator of the hypothalamic-pituitary-adrenocortical axis.

PMID- 16899056
TI  - Cardiac resynchronization therapy in the young patient: current status and future
      directions.

PMID- 16899055
TI  - Impaired postnatal development of hippocampal dentate gyrus in Sp4 null mutant
      mice.
AB  - Sp4, a member of the Sp1 family of transcription factors, is expressed
      restrictively in the developing nervous system and abundantly in the hippocampus.
      Previously, we demonstrated that hypomorphic Sp4 mice display hippocampal
      vacuolization and concomitant deficits in memory and sensorimotor gating. Here,
      we report further analyses of Sp4 functions during postnatal development of the
      dentate gyrus in Sp4 null mutant mice. A reduced cell proliferation restrictively
      in hippocampus, but not cerebellum, was observed in the first week of postnatal
      development of Sp4 null mutant mice. The dendritic growth and arborization of
      dentate granule cells was decreased in hippocampal cultures in vitro from mutant
      neonatal mice. The adult Sp4 null mutant mice displayed decreased dentate granule
      cell density with reduced width of both dentate gyrus and the molecular layer.
      The abnormality of the molecular layer was indicated by a reduced level of
      synaptophysin expression in the mutant mice. The Sp4 transcription factor
      therefore appears to predominantly regulate the development of dentate granule
      cells.

PMID- 16899053
TI  - Increased response to morphine in mice lacking protein kinase C epsilon.
AB  - The protein kinase C (PKC) family of serine-threonine kinases has been implicated
      in behavioral responses to opiates, but little is known about the individual PKC
      isozymes involved. Here, we show that mice lacking PKCepsilon have increased
      sensitivity to the rewarding effects of morphine, revealed as the expression of
      place preference and intravenous self-administration at very low doses of
      morphine that do not evoke place preference or self-administration in wild-type
      mice. The PKCepsilon null mice also show prolonged maintenance of morphine place
      preference in response to repeated testing when compared with wild-type mice. The
      supraspinal analgesic effects of morphine are enhanced in PKCepsilon null mice,
      and the development of tolerance to the spinal analgesic effects of morphine is
      delayed. The density of mu-opioid receptors and their coupling to G-proteins are
      normal. These studies identify PKCepsilon as a key regulator of opiate
      sensitivity in mice.

PMID- 16899057
TI  - Another way to prove the presence and participation of an accessory pathway in
      supraventricular tachycardia?

PMID- 16899058
TI  - A SYBR green-based real-time PCR method for detection of haemopoietic chimerism
      in allogeneic haemopoietic stem cell transplant recipients.
AB  - OBJECTIVE: To develop a reliable and rapid real-time quantitative polymerase
      chain reaction (Q-PCR) method using SYBR green to quantify chimerism in
      allogeneic haemopoietic stem cell transplant recipients. METHODS: Twelve specific
      nucleotide polymorphisms (NPs) were selected to identify informative markers for
      detecting chimerism in transplant donor/recipient pairs. One informative marker
      was then used in SYBR green Q-PCR to detect chimerism post-transplantation in
      each patient. The percentage of donor cells was calculated using a standard
      curve, constructed using artificially mixed donor/recipient chimeric DNA in 12
      serial dilutions (0.01-100%). RESULTS: DNA from 37 donor/recipient pairs was
      screened for informative markers and 18 post-transplant samples were monitored
      for chimerism with SYBR green Q-PCR method. The Q-PCR was able to discriminate
      between recipient and donor genetic profiles in all 18 samples, and quantify the
      chimerism. These results were confirmed by at least one independent method, such
      as TaqMan Q-PCR, microsatellite and fluorescent in situ hybridisation (FISH)
      methods. The detection limit of this method was 0.1%, which was more sensitive
      than the two currently used microsatellite and FISH methods. CONCLUSION: The new
      single platform SYBR green Q-PCR method is capable of detecting all haemopoietic
      chimerism with high accuracy; hence, it may be used to replace the current
      detection methods.

PMID- 16899059
TI  - Race and gender differences in general internists' annual incomes.
AB  - BACKGROUND: Specialty, work effort, and female gender have been shown to be
      associated with physicians' annual incomes; however, racial differences in
      physician incomes have not been examined. OBJECTIVE: To determine the influence
      of race and gender on General Internists' annual incomes after controlling for
      work effort, provider characteristics, and practice characteristics. DESIGN:
      Retrospective survey-weighted analysis of survey data. PARTICIPANTS: One thousand
      seven hundred and forty-eight actively practicing General Internists who
      responded to the American Medical Association's annual survey of physicians
      between 1992 and 2001. MEASUREMENTS: Work effort, provider and practice
      characteristics, and adjusted annual incomes for white male, black male, white
      female, and black female General Internists. RESULTS: Compared with white males,
      white females completed 22% fewer patient visits and worked 12.5% fewer hours,
      while black males and females reported completing 17% and 2.8% more visits and
      worked 15% and 5.5% more annual hours, respectively. After adjustment for work
      effort, provider characteristics, and practice characteristics, black males' mean
      annual income was 188,831 dollars or 7,193 dollars (4%) lower than that for white
      males (95% CI: -31,054 dollars, 16,669 dollars; P=.6); white females' was 159,415
      dollars or 36,609 dollars (19%) lower (95% CI: -25,585 dollars, -47,633 dollars;
      P<.001); and black females' was 139,572 dollars or 56,452 dollars (29%) lower
      (95% CI: -93,383 dollars, -19,520 dollars; P=.003). CONCLUSIONS: During the
      1990s, both black race and female gender were associated with lower annual
      incomes among General Internists. Differences for females were substantial. These
      findings warrant further exploration.

PMID- 16899062
TI  - N-Arachidonyl-glycine inhibits the glycine transporter, GLYT2a.
AB  - N-arachidonyl-glycine is one of a series of N-arachidonyl-amino acids that are
      derived from arachidonic acid. N-arachidonyl-glycine is produced in a wide range
      of tissues with greatest abundance in the spinal cord. Here we report that N
      arachidonyl-glycine is a reversible and non-competitive inhibitor of glycine
      transport by GLYT2a, but has little effect on glycine transport by GLYT1b or
      gamma-amino butyric acid transport by GAT1. It has previously been reported that
      the activity of GLYT2a is down-regulated by protein kinase C and therefore we
      investigated whether the actions of N-arachidonyl-glycine on GLYT2a are mediated
      by second messenger systems that lead to the activation of protein kinase C.
      However, the protein kinase C inhibitor, staurosporine, had no effect on the
      actions of N-arachidonyl-glycine on GLYT2a. Thus, the actions of N-arachidonyl
      glycine are likely to be mediated by a direct interaction with the transporter.
      We have further defined the pharmacophore by investigating the actions of other N
      arachidonyl amino acids as well as the closely related compounds arachidonic
      acid, anandamide and R1-methanandamide. Arachidonic acid, anandamide and R1
      methanandamide have no effect on glycine transport, but N-arachidonyl-l-alanine
      has similar efficacy at GLYT2a to N-arachidonyl-glycine, and N-arachidonyl-gamma
      amino butyric acid is less efficacious. These observations define a novel
      recognition site for the N-arachidonyl amino acids.

PMID- 16899063
TI  - Acyl-based anandamide uptake inhibitors cause rapid toxicity to C6 glioma cells
      at pharmacologically relevant concentrations.
AB  - Compounds blocking the uptake of the endogenous cannabinoid anandamide (AEA) have
      been used to explore the functions of the endogenous cannabinoid system in the
      CNS both in vivo and in vitro. In this study, the effects of four commonly used
      acyl-based uptake inhibitors [N-(4-hydroxyphenyl)arachidonylamide (AM404), N-(4
      hydroxy-2-methylphenyl) arachidonoyl amide (VDM11), (5Z,8Z,11Z,14Z)-N-(3
      furanylmethyl)-5,8,11,14-eicosatetraenamide (UCM707) and (9Z)-N-[1-((R)-4
      hydroxybenzyl)-2-hydroxyethyl]-9-octadecen-amide (OMDM2)] and the related
      compound arvanil on C6 glioma cell viability were investigated. All five
      compounds reduced the ability of the cells to accumulate calcein, reduced the
      total nucleic acid content and increased the activity of lactate dehydrogenase
      recovered in the cell medium. AM404 (10 microm) and VDM11 (10 microm) acted
      rapidly, reducing cell viability after 3 h of exposure when cell densities of
      5,000 per well were used. In contrast, UCM707 (30 microm), OMDM2 (10 microm) and
      the related compound arvanil (10 microm) produced a more slowly developing effect
      on cell viability, although robust effects were seen after 6-9 h of exposure. At
      higher cell densities, the toxicities of AM404 and UCM707 were reduced.
      Comparison of the compounds with arachidonic acid, arachidonic acid methyl ester,
      AEA, arachidonoyl glycine and oleic acid suggested that the toxicity of the
      arachidonoyl-based compounds was related primarily to the acyl side-chain rather
      than the head group. A variety of pre-treatments blocking possible metabolic
      pathways and receptor targets were tested, but the only consistent protective
      treatment against the effects of these compounds was the antioxidant N-acetyl-L
      cysteine. It is concluded that AM404, VDM11, UCM707 and OMDM2 produce a rapid
      loss of C6 glioma cell viability over the same concentration range as is required
      for the inhibition of AEA uptake in vitro, albeit with a longer latency. Such
      effects should be kept in mind when acyl-derived compounds are used to probe the
      function of the endocannabinoid system in the CNS, particularly in chronic
      administration protocols.

PMID- 16899061
TI  - Persistent depression affects adherence to secondary prevention behaviors after
      acute coronary syndromes.
AB  - BACKGROUND: The persistence of depressive symptoms after hospitalization is a
      strong risk factor for mortality after acute coronary syndromes (ACS). Poor
      adherence to secondary prevention behaviors may be a mediator of the relationship
      between depression and increased mortality. OBJECTIVE: To determine whether rates
      of adherence to risk reducing behaviors were affected by depressive status during
      hospitalization and 3 months later. DESIGN: Prospective observational cohort
      study. SETTING: Three university hospitals. PARTICIPANTS: Five hundred and sixty
      patients were enrolled within 7 days after ACS. Of these, 492 (88%) patients
      completed 3-month follow-up. MEASUREMENTS: We used the Beck Depression Inventory
      (BDI) to assess depressive symptoms in the hospital and 3 months after discharge.
      We assessed adherence to 5 risk-reducing behaviors by patient self-report at 3
      months. We used chi2 analysis to compare differences in adherence among 3 groups:
      persistently nondepressed (BDI < 10 at hospitalization and 3 months); remittent
      depressed (BDI > or = 10 at hospitalization; < 10 at 3 months); and persistently
      depressed patients (BDI > or = 10 at hospitalization and 3 months). RESULTS:
      Compared with persistently nondepressed, persistently depressed patients reported
      lower rates of adherence to quitting smoking (adjusted odds ratio [OR] 0.23, 95%
      confidence interval [95% CI] 0.05 to 0.97), taking medications (adjusted OR 0.50,
      95% CI 0.27 to 0.95), exercising (adjusted OR 0.57, 95% CI 0.34 to 0.95), and
      attending cardiac rehabilitation (adjusted OR 0.5, 95% CI 0.27 to 0.91). There
      were no significant differences between remittent depressed and persistently
      nondepressed patients. CONCLUSIONS: Persistently depressed patients were less
      likely to adhere to behaviors that reduce the risk of recurrent ACS. Differences
      in adherence to these behaviors may explain in part why depression predicts
      mortality after ACS.

PMID- 16899064
TI  - Developmental and cell-selective variations in N-methyl-D-aspartate receptor
      degradation by calpain.
AB  - NMDA receptors play critical roles in synaptic modulation and neurological
      disorders. In this study, we investigated the developmental changes in NR2
      cleavage by NMDA receptor-activated calpain in cultured cortical and hippocampal
      neurons. Calpain activity increased with development, associated with increased
      expression of NMDA receptors but not of calpain I. The activation of calpain in
      immature and mature cortical cultures was inhibited by antagonists of NR1/2B and
      NR1/2A/2B receptors, whereas the inhibition of NR1/2B receptors did not alter
      calpain activation in mature hippocampal cultures. The degradation of NR2
      subunits by calpain differed with developmental age. NR2A was not a substrate of
      calpain in mature hippocampal cultures, but was cleaved in immature cortical and
      hippocampal cultures. NR2B degradation by calpain in cortical cultures decreased
      with development, but the level of degradation of NR2B in hippocampal cultures
      did not change. The kinetics of NMDA receptor-gated whole cell currents were also
      modulated by calpain activation in a manner that varied with developmental stage
      in vitro. In early (but not later) developmental stages, calpain activation
      altered the NMDA-evoked current rise time and time constants for both
      desensitization and deactivation. Our data suggest that the susceptibility of the
      NMDA receptor to cleavage by calpain varies with neuronal maturity in a manner
      that may alter its electrophysiological properties.

PMID- 16899065
TI  - Function of the rat carotid body chemoreceptors in ageing.
AB  - Some age-related deficits in the ventilatory responses have been attributed to a
      decline in the functionality of the carotid body (CB) arterial chemoreceptors,
      but a systematic study of the CB function in ageing is lacking. In rats aged 3-24
      months, we have performed quantitative morphometry on specific chemoreceptor
      tissue, assessed the function of chemoreceptor cells by measuring the content,
      synthesis and release of catecholamines (a chemoreceptor cell neurotransmitter)
      in normoxia and hypoxia, and determined the functional activity of the intact
      organ by measuring chemosensory activity in the carotid sinus nerve (CSN) in
      normoxia, hypoxia and hypercapnic acidosis. We found that with age CBs enlarge,
      but at the same time there is a concomitant decrease in the percentage of
      chemoreceptor tissue. CB content and turnover time for their catecholamines
      increase with age. Hypoxic stimulation of chemoreceptor cells elicits a smaller
      release of catecholamines in rats after 12 months of age, but a non-specific
      depolarizing stimulus elicits a comparable release at all ages. In parallel,
      there was a marked decrease in the responsiveness to hypoxia, but not to an
      acidic-hypercapnic stimulus, assessed as chemosensory activity in the CSN. We
      conclude that in aged mammals chemoreceptor cells become hypofunctional, leading
      to a decreased peripheral drive of ventilation.

PMID- 16899067
TI  - Retrograde signaling in injured nerve--the axon reaction revisited.
AB  - Injury to axons elicits changes in macromolecule synthesis in the corresponding
      cell bodies that are critical for an effective regenerative response. For decades
      the most easily studied aspect of this phenomenon was the onset of chromatolysis,
      a suite of structural changes in the cell body characterized by swelling,
      shifting of the nucleus and dispersal of Nissl bodies. The question: 'what is the
      signal for chromatolysis?' received no less than 10 possible answers in a
      comprehensive review article published more than three decades ago. Here we come
      back to this 36 years old question, and review progress on understanding the
      mechanism of retrograde injury signaling in lesioned peripheral nerves. Recent
      work suggests that this is based on local axonal synthesis of critical carrier
      proteins, including importins and vimentin that link diverse signaling molecules
      to the dynein retrograde motor. A multiplicity of binding sites and of potential
      signaling molecules, including transcription factors and MAP kinases (Erk, Jnk),
      may allow diverse options for information-rich encoding of the injury status of
      the axon for transmission to the cell body.

PMID- 16899066
TI  - Anatomical distribution and biochemical characterization of the novel RFamide
      peptide 26RFa in the human hypothalamus and spinal cord.
AB  - 26RFa is a novel RFamide peptide originally isolated in the amphibian brain. The
      26RFa precursor has been subsequently characterized in various mammalian species
      but, until now, the anatomical distribution and the molecular forms of 26RFa
      produced in the CNS of mammals, in particular in human, are unknown. In the
      present study, we have investigated the localization and the biochemical
      characteristics of 26RFa-like immunoreactivity (LI) in two regions of the human
      CNS--the hypothalamus and the spinal cord. Immunohistochemical labeling using
      specific antibodies against human 26RFa and in situ hybridization histochemistry
      revealed that in the human hypothalamus 26RFa-expressing neurons are located in
      the paraventricular and ventromedial nuclei. In the spinal cord, 26RFa-expressing
      neurons were observed in the dorsal and lateral horns. Characterization of 26RFa
      related peptides showed that two distinct molecular forms of 26RFa are present in
      the human hypothalamus and spinal cord, i.e. 26RFa and an N-terminally elongated
      form of 43 amino acids designated 43RFa. These data provide the first evidence
      that 26RFa and 43RFa are actually produced in the human CNS. The distribution of
      26RF-LI suggests that 26RFa and/or 43RFa may modulate feeding, sexual behavior
      and transmission of nociceptive stimuli.

PMID- 16899068
TI  - Glucose metabolism and proliferation in glia: role of astrocytic gap junctions.
AB  - Astrocytes play a well-established role in brain metabolism, being a key element
      in the capture of energetic compounds from the circulation and in their delivery
      to active neurons. Their metabolic status is affected in many pathological
      situations, such as gliomas, which are the most common brain tumors. This
      proliferative dysfunction is associated with changes in gap junctional
      communication, a property strongly developed in normal astrocytes studied both in
      vitro and in vivo. Here, we summarize and discuss the findings that have lead to
      the identification of a link between gap junctions, glucose uptake, and
      proliferation. Indeed, the inhibition of gap junctional communication is
      associated with an increase in glucose uptake due to a rapid change in the
      localization of both GLUT-1 and type I hexokinase. This effect persists due to
      the up-regulation of GLUT-1 and type I hexokinase and to the induction of GLUT-3
      and type II hexokinase. In addition, cyclins D1 and D3 have been found to act as
      sensors of the inhibition of gap junctions and have been proposed to play the
      role of mediators in the mitogenic effect observed. Conversely, in C6 glioma
      cells, characterized by a low level of intercellular communication, an increase
      in gap junctional communication reduces glucose uptake by releasing type I and
      type II hexokinases from the mitochondria and decreases the exacerbated rate of
      proliferation due to the up-regulation of the Cdk inhibitors p21 and p27.
      Identification of the molecular actors involved in these pathways should allow
      the determination of potential therapeutic targets that could lead to the testing
      of alternative strategies to prevent, or at least slow down, the proliferation of
      glioma cells.

PMID- 16899069
TI  - Identification of developmentally regulated expression of MuSK in astrocytes of
      the rodent retina.
AB  - One of the master regulators of postsynaptic neuromuscular synaptogenesis is the
      muscle-specific receptor tyrosine kinase (MuSK). In mammals prominent MuSK
      expression is believed to be restricted to skeletal muscle. Upon activation by
      nerve-derived agrin MuSK-dependent signalling participates in both the induction
      of genes encoding postsynaptic components and aggregation of nicotinic
      acetylcholine receptors (AChR) in the subsynaptic muscle membrane. Strikingly,
      expression of certain isoforms of nerve-derived agrin can also be detected in the
      CNS. In this study, we examined the expression of MuSK in the brain and eye of
      rodents. In the retina MuSK was expressed in astrocytes between postnatal days 7
      and 14, i.e. at the time when the eyes open. We found that agrin was localized
      adjacent to MuSK-expressing astrocytes which in turn were detected close to the
      inner limiting membrane of the rodent retina. In summary, the presence of MuSK on
      retinal astrocytes suggests a novel role of MuSK signalling pathways in the CNS.

PMID- 16899070
TI  - Neonicotinoid insecticides display partial and super agonist actions on native
      insect nicotinic acetylcholine receptors.
AB  - Nicotinic acetylcholine receptors (nAChRs) are present in high density in insect
      nervous tissue and are targeted by neonicotinoid insecticides. Improved
      understanding of the actions of these insecticides will assist in the development
      of new compounds. Here, we have used whole-cell patch-clamp recording of
      cholinergic neurons cultured from the central nervous system of 3rd instar
      Drosophila larvae to examine the actions of acetylcholine (ACh) and nicotine, as
      well as the neonicotinoids imidacloprid, clothianidin and P-CH-clothianidin on
      native nAChRs of these neurons. Dose-response data yield an EC(50) value for ACh
      of 19 microm. Both nicotine and imidacloprid act as low efficacy agonists at
      native nAChRs, evoking maximal current amplitudes 10-14% of those observed for
      ACh. Conversely, clothianidin and P-CH-clothianidin evoke maximal current
      amplitudes up to 56% greater than those evoked by 100 microm ACh in the same
      neurons. This is the first demonstration of 'super' agonist actions of an
      insecticide on native insect nAChRs. Cell-attached recordings indicate that super
      agonism results from more frequent openings at the largest (63.5 pS) conductance
      state observed.

PMID- 16899071
TI  - Antigen-specific therapy promotes repair of myelin and axonal damage in
      established EAE.
AB  - Inflammation results in CNS damage in multiple sclerosis (MS) and experimental
      autoimmune encephalomyelitis (EAE), an animal model of MS. It is uncertain how
      much repair of injured myelin and axons can occur following highly selective anti
      inflammatory therapy in EAE and MS. In this study, SJL/J mice with established
      EAE were treated successfully with an antigen-specific recombinant T cell
      receptor ligand (RTL), RTL401, a mouse I-A(s)/PLP-139-151 construct, after the
      peak of EAE. To define the mechanisms by which late application of RTL401
      inhibits EAE, we evaluated mice at different time points to assess the levels of
      neuroinflammation and myelin and axon damage in their spinal cords. Our results
      showed that RTL401 administered after the peak of acute EAE induced a marked
      reduction in inflammation in the CNS, associated with a significant reduction of
      demyelination, axonal loss and ongoing damage. Electron microscopy showed that
      RTL-treated mice had reduced pathology compared with mice treated with vehicle
      and mice at the peak of disease, as demonstrated by a decrease in continued
      degeneration, increase in remyelinating axons and the presence of an increased
      number of small, presumably regenerative axonal sprouts. These findings indicate
      that RTL therapy targeting encephalitogenic T cells may promote CNS
      neuroregenerative processes.

PMID- 16899073
TI  - Reduced NMDA receptor tyrosine phosphorylation in PTPalpha-deficient mouse
      synaptosomes is accompanied by inhibition of four src family kinases and Pyk2: an
      upstream role for PTPalpha in NMDA receptor regulation.
AB  - Mice lacking protein tyrosine phosphatase alpha (PTPalpha) exhibited defects in
      NMDA receptor (NMDAR)-associated processes such as learning and memory,
      hippocampal neuron migration, and CA1 hippocampal long-term potentiation (LTP).
      In vivo molecular effectors linking PTPalpha and the NMDAR have not been
      reported. Thus the involvement of PTPalpha as an upstream regulator of NMDAR
      tyrosine phosphorylation was investigated in synaptosomes of wild-type and
      PTPalpha-null mice. Tyrosine phosphorylation of the NMDAR NR2A and NR2B subunits
      was reduced upon PTPalpha ablation, indicating a positive effect of this
      phosphatase on NMDAR phosphorylation via intermediate molecules. The NMDAR is a
      substrate of src family tyrosine kinases, and reduced activity of src, fyn, yes
      and lck, but not lyn, was apparent in the absence of PTPalpha. In addition,
      autophosphorylation of proline-rich tyrosine kinase 2 (Pyk2), a tyrosine kinase
      linked to NMDAR signaling, was also reduced in PTPalpha-deficient synaptosomes.
      Altered protein tyrosine phosphorylation was not accompanied by altered
      expression of the NMDAR or the above tyrosine kinases at any stage of PTPalpha
      null mouse development examined. In a human embryonic kidney (HEK) 293 cell
      expression system, PTPalpha enhanced fyn-mediated NR2A and NR2B tyrosine
      phosphorylation by several-fold. Together, these findings provide evidence that
      aberrant NMDAR-associated functions in PTPalpha-null mice are due to impaired
      NMDAR tyrosine phosphorylation resulting from the reduced activity of probably
      more than one of the src family kinases src, fyn, yes and lck. Defective NMDAR
      activity in these mice may also be linked to the loss of PTPalpha as an upstream
      regulator of Pyk2.

PMID- 16899074
TI  - Actin-associated neurabin-protein phosphatase-1 complex regulates hippocampal
      plasticity.
AB  - Protein phosphatase-1 (PP1) has been implicated in the control of long-term
      potentiation (LTP) and depression (LTD) in rat hippocampal CA1 neurons. PP1
      catalytic subunits associate with multiple postsynaptic regulatory subunits, but
      the PP1 complexes that control hippocampal LTP and LTD in the rat hippocampus
      remain unidentified. The neuron-specific actin-binding protein, neurabin-I, is
      enriched in dendritic spines, and tethers PP1 to actin-rich postsynaptic density
      to regulate morphology and maturation of spines. The present studies utilized
      Sindbis virus-mediated expression of wild-type and mutant neurabin-I polypeptides
      in organotypic cultures of rat hippocampal slices to investigate their role in
      synaptic plasticity. While wild-type neurabin-I elicited no change in basal
      synaptic transmission, it enhanced LTD and inhibited LTP in CA1 pyramidal
      neurons. By comparison, mutant neurabins, specifically those unable to bind PP1
      or F-actin, decreased basal synaptic transmission, attenuated LTD and increased
      LTP in slice cultures. Biochemical and cell biological analyses suggested that,
      by mislocalizing synaptic PP1, the mutant neurabins impaired the functions of
      endogenous neurabin-PP1 complexes and modulated LTP and LTD. Together, these
      studies provided the first biochemical and physiological evidence that a
      postsynaptic actin-bound neurabin-I-PP1 complex regulates synaptic transmission
      and bidirectional changes in hippocampal plasticity.

PMID- 16899072
TI  - The role of Toll-like receptors in CNS response to microbial challenge.
AB  - The recent discovery of the family of Toll-like receptors has vastly expanded our
      understanding of the mechanisms by which the innate immune system recognizes and
      responds to a wide variety of microbial and endogenous pathogens. Toll-like
      receptors are transmembrane proteins that upon ligation with their cognate
      ligands trigger the production of cytokines, enzymes and other inflammatory
      agents. In the CNS Toll-like receptors are expressed predominantly by glial
      cells. In particular, the vastly abundant astrocytes are likely to be the major
      contributors to inflammatory responses within the CNS. Studies of the murine
      brain abscess model revealed that Toll-like receptor 2 plays a pivotal role in
      the generation of immune responses to Staphylococcus aureus. Although Toll-like
      receptor signaling is essential in antimicrobial defense, it may also lead to
      bystander injury of CNS tissue.

PMID- 16899075
TI  - Decreased brain damage and curtailed inflammation in transcription factor
      CCAAT/enhancer binding protein beta knockout mice following transient focal
      cerebral ischemia.
AB  - CCAAT/enhancer binding protein beta (C/EBPbeta) is a leucine-zipper transcription
      factor that regulates cell growth and differentiation in mammals. Expression of
      many pro-inflammatory genes including the cytokine interleukin-6 is known to be
      controlled by C/EBPbeta. We report that focal cerebral ischemia induced by
      transient middle cerebral artery occlusion (MCAO) significantly increases
      C/EBPbeta gene expression in mouse brain at between 6 and 72 h of reperfusion. To
      understand the functional significance of C/EBPbeta in postischemic inflammation
      and brain damage, we induced transient MCAO in cohorts of adult C/EBPbeta null
      mice and their wild-type littermates. At 3 days of reperfusion following
      transient MCAO, C/EBPbeta null mice showed significantly smaller infarcts,
      reduced neurological deficits, decreased terminal deoxynucleotidyl transferase
      mediated dUTP nick-end labeling-positive cells, decreased intercellular adhesion
      molecule 1 (ICAM1) immunopositive vessels, decreased extravasated neutrophils and
      fewer activated microglia/macrophages, compared with their wild-type littermates.
      Furthermore, GeneChip analysis showed that postischemic induction of many
      transcripts known to promote inflammation and neuronal damage was less pronounced
      in the brains of C/EBPbeta-/- mice compared with C/EBPbeta+/+ mice. These results
      suggest a significant role for C/EBPbeta in postischemic inflammation and brain
      damage.

PMID- 16899076
TI  - A phase-variable mechanism controlling the Campylobacter jejuni FlgR response
      regulator influences commensalism.
AB  - Phase variation of genes in bacteria enables phenotypic alteration to modulate
      interactions within a host as conditions change. To promote commensalism in
      animals and disease in humans, Campylobacter jejuni produces a flagellar
      organelle for motility. In addition to tight transcriptional regulation of
      flagellar genes, C. jejuni also controls flagellar biosynthesis by phase
      variation. In this study, an unusual phase-variable mechanism controlling
      production of FlgR, the response regulator of the FlgSR two-component system
      required for transcription of sigma54-dependent flagellar genes, is identified.
      Phase variation of FlgR production is due to loss or gain of a nucleotide in
      homopolymeric adenine or thymine tracts within flgR. This mechanism occurs during
      commensalism in poultry to alter the colonization capacity of C. jejuni,
      presumably by influencing the motility phenotype of the bacterium. These findings
      provide more understanding into the genetic and colonization strategies C. jejuni
      employs to achieve commensalism in a natural host. Second, due to the richness of
      the C. jejuni genome in adenine or thymine residues and the apparent lack of the
      normal set of mismatch repair enzymes, the results from this study may suggest
      that the C. jejuni genome is more unstable and variable than previously realized.
      Furthermore, phase variation of flagellar motility by targeting flgR may be a
      phenomenon specific to C. jejuni that is absent in other Campylobacter species
      and contribute to reasons why C. jejuni is more frequently found as a commensal
      organism in poultry and as the cause of disease in humans.

PMID- 16899077
TI  - Thioredoxin reductase is required for growth and regulates entry into culmination
      of Dictyostelium discoideum.
AB  - The thioredoxin system, consisting of thioredoxin, thioredoxin reductase and
      NADPH, has been well established to be critical for the redox regulation of
      protein function and signalling. To investigate the role of thioredoxin reductase
      (Trr) in Dictyostelium discoideum, we generated mutant cells that underexpress or
      overexpress Trr. Trr-underexpressing cells exhibited severe defects in axenic
      growth and development. Trr-overexpressing (TrrOE) cells formed very tiny plaques
      on a bacterial lawn and had a lower rate of bacterial uptake. When developed in
      the dark, TrrOE cells exhibited a slugger phenotype, defined by a prolonged
      migrating slug stage. Like other slugger mutants, they were hypersensitive to
      ammonia, which has been known to inhibit culmination by raising the pH of
      intracellular acidic compartments. Interestingly, TrrOE cells showed defective
      acidification of intracellular compartments and decreased activity of vacuolar H+
      ATPase which functions in the acidification of intracellular compartments.
      Moreover, biochemical studies revealed that the thioredoxin system can directly
      reduce the catalytic subunit of vacuolar H+-ATPase whose activity is regulated by
      reversible disulphide bond formation. Taken together, these results suggest that
      Dictyostelium Trr may be essential for growth and play a role in regulation of
      phagocytosis and culmination, possibly through the modulation of vacuolar H+
      ATPase activity.

PMID- 16899078
TI  - The minor capsid protein gp7 of bacteriophage SPP1 is required for efficient
      infection of Bacillus subtilis.
AB  - Gp7 is a minor capsid protein of the Bacillus subtilis bacteriophage SPP1.
      Homologous proteins are found in numerous phages but their function remained
      unknown. Deletion of gene 7 from the SPP1 genome yielded a mutant phage
      (SPP1del7) with reduced burst-size. SPP1del7 infections led to normal assembly of
      virus particles whose morphology, DNA and protein composition was
      undistinguishable from wild-type virions. However, only approximately 25% of the
      viral particles that lack gp7 were infectious. SPP1del7 particles caused a
      reduced depolarization of the B. subtilis membrane in infection assays suggesting
      a defect in virus genome traffic to the host cell. A higher number of SPP1del7
      DNA ejection events led to abortive release of DNA to the culture medium when
      compared with wild-type infections. DNA ejection in vitro showed that no
      detectable gp7 is co-ejected with the SPP1 genome and that its presence in the
      virion correlated with anchoring of released DNA to the phage particle. The
      release of DNA from wild-type phages was slower than that from SPP1del7
      suggesting that gp7 controls DNA exit from the virion. This feature is proposed
      to play a central role in supporting correct routing of the phage genome from the
      virion to the cell cytoplasm.

PMID- 16899079
TI  - Involvement of Clp protease activity in modulating the Bacillus subtilissigmaw
      stress response.
AB  - The induction of Bacillus subtilis genes controlled by the extracytoplasmic
      function alternative sigma factor sigmaW is strongly impaired in a strain deleted
      for the ClpP peptidase gene and in a double knockout of the ClpX and ClpE ATPase
      genes. Truncated soluble forms of the sigmaW anti-sigma factor RsiW are
      stabilized in a clpP minus strain as revealed by the green fluorescent reporter
      protein fused to the N-terminus of RsiW and by pulse-chase experiments. Conserved
      alanine residues are present in the transmembrane region of RsiW, and mutations
      in these positions abolish induction of sigmaW-controlled genes. Following
      alkaline shock, a truncated cytoplasmic form of RsiW is detectable in a strain
      expressing a triple alanine mutant allele of rsiW. These data point to a
      mechanism where the trans-membrane segment of RsiW contains a cryptic proteolytic
      tag that is uncovered as a result of intramembrane proteolysis of RsiW by RasP
      (YluC). After RasP-clipped RsiW is detached from the membrane, this proteolytic
      tag becomes crucial for the complete degradation of RsiW by cytoplasmic proteases
      and the release of sigmaW. ClpXP plays a major role in this third proteolytic
      step of stress-induced degradation of RsiW. Overexpression of SsrA-tagged green
      fluorescent protein as a ClpXP substrate protein reduces alkali induction of a
      sigmaW-controlled gene by a factor of about three, indicating that a titration
      mechanism is able to tune the sigmaW-mediated stress response to the cellular
      state.

PMID- 16899080
TI  - Regular cellular distribution of plasmids by oscillating and filament-forming
      ParA ATPase of plasmid pB171.
AB  - Centromere-like loci from bacteria segregate plasmids to progeny cells before
      cell division. The ParA ATPase (a MinD homologue) of the par2 locus from plasmid
      pB171 forms oscillating helical structures over the nucleoid. Here we show that
      par2 distributes plasmid foci regularly along the length of the cell even in
      cells with many plasmids. In vitro, ParA binds ATP and ADP and has a cooperative
      ATPase activity. Moreover, ParA forms ATP-dependent filaments and cables,
      suggesting that ParA can provide the mechanical force for the observed regular
      distribution of plasmids. ParA and ParB interact with each other in a bacterial
      two-hybrid assay but do not interact with FtsZ, eight other essential cell
      division proteins or MreB actin. Based on these observations, we propose a simple
      model for how oscillating ParA filaments can mediate regular cellular
      distribution of plasmids. The model functions without the involvement of
      partition-specific host cell receptors and is thus consistent with the striking
      observation that partition loci can function in heterologous host organisms.

PMID- 16899081
TI  - MAMPs and MIMPs: proposed classifications for inducers of innate immunity.
AB  - Plants encode a sophisticated innate immune system. Resistance against potential
      pathogens often relies on active responses. Prerequisite to the induction of
      defences is recognition of the pathogenic threat. Significant advances have been
      made in our understanding of the non-self molecules that are recognized by plants
      and the means by which plants perceive them. Established terms describing these
      recognition events, including microbe-associated molecular pattern (MAMP), MAMP
      receptor, effector, and resistance (R) protein, need clarification to represent
      our current knowledge adequately. In this review we propose criteria to classify
      inducers of plant defence as either MAMPs or microbe-induced molecular patterns
      (MIMPs). We refine the definition of MAMP to mean a molecular sequence or
      structure in ANY pathogen-derived molecule that is perceived via direct
      interaction with a host defence receptor. MIMPs are modifications of host-derived
      molecules that are induced by an intrinsic activity of a pathogen-derived
      effector and are perceived by a host defence receptor. MAMP-receptors have
      previously been classified separately from R-proteins as a discrete class of
      surveillance molecules. However, MAMP-receptors and R-proteins cannot be
      distinguished on the basis of their protein structures or their induced
      responses. We propose that MAMP-receptors and MIMP-receptors are each a subset of
      R-proteins. Although our review is based on examples from plant pathogens and
      plants, the principles discussed might prove applicable to other organisms.

PMID- 16899082
TI  - Circadian control of isoprene emissions from oil palm (Elaeis guineensis).
AB  - The emission of isoprene from the biosphere to the atmosphere has a profound
      effect on the Earth's atmospheric system. Until now, it has been assumed that the
      primary short-term controls on isoprene emission are photosynthetically active
      radiation and temperature. Here we show that isoprene emissions from a tropical
      tree (oil palm, Elaeis guineensis) are under strong circadian control, and that
      the circadian clock is potentially able to gate light-induced isoprene emissions.
      These rhythms are robustly temperature compensated with isoprene emissions still
      under circadian control at 38 degrees C. This is well beyond the acknowledged
      temperature range of all previously described circadian phenomena in plants.
      Furthermore, rhythmic expression of LHY/CCA1, a genetic component of the central
      clock in Arabidopsis thaliana, is still maintained at these elevated temperatures
      in oil palm. Maintenance of the CCA1/LHY-TOC1 molecular oscillator at these
      temperatures in oil palm allows for the possibility that this system is involved
      in the control of isoprene emission rhythms. This study contradicts the accepted
      theory that isoprene emissions are primarily light-induced.

PMID- 16899083
TI  - Identification of an allene oxide synthase (CYP74C) that leads to formation of
      alpha-ketols from 9-hydroperoxides of linoleic and linolenic acid in below-ground
      organs of potato.
AB  - Allene oxide synthase (AOS) enzymes are members of the cytochrome P450 enzyme
      family, sub-family CYP74. Here we describe the isolation of three cDNAs encoding
      AOS from potato (StAOS1-3). Based on sequence comparisons, they represent members
      of either the CYP74A (StAOS1 and 2) or the CYP74C (StAOS3) sub-families. StAOS3
      is distinguished from the other two AOS isoforms in potato by its high substrate
      specificity for 9-hydroperoxides of linoleic and linolenic acid, compared with 13
      hydroperoxides, which are only poor substrates. The highest activity was shown
      with (9S,10E,12Z)-9-hydroperoxy-10,12-octadecadienoic acid (9-HPODE) as a
      substrate. This hydroperoxide was metabolized in vitro to alpha- and gamma-ketols
      as well as to the cyclopentenone compound 10-oxo-11-phytoenoic acid. They
      represent hydrolysis products of the initial StAOS3 product 9,10
      epoxyoctadecadienoic acid, an unstable allene oxide. By RNA gel hybridization
      blot analysis, StAOS3 was shown to be expressed in sprouting eyes, stolons,
      tubers and roots, but not in leaves. StAOS3 protein was found in all organs
      tested, but mainly in stems, stolons, sprouting eyes and tubers. As in vivo
      reaction products, the alpha-ketols derived from 9-hydroperoxides of linoleic and
      linolenic acid were only found in roots, tubers and sprouting eyes.
      Immunolocalization showed that StAOS3 was associated with amyloplasts and
      leucoplasts.

PMID- 16899084
TI  - Homoeologous gene silencing in hexaploid wheat.
AB  - The vast majority of angiosperms are (or were once) polyploid, and as hexaploid
      bread wheat has undergone two ploidy events separated by approximately 0.5
      million years, it represents an elegant model to study gene silencing over time
      in polyploids. Using an SSCP platform, we have analysed patterns of
      transcriptional silencing (frequency, genome identity and organ specificity)
      within 236 single-copy genes, each mapping to one locus on one of the three
      homoeologous chromosomes within groups 1, 2, 3 and 7 of wheat. In about 27% of
      unigenes expressed in leaf, and about 26% of those in root, one (rarely two)
      members of a gene set (homoeoalleles) were not present in the cDNA template.
      Organ-specific regulation is commonplace, with many homoeoalleles transcribed in
      leaf but not root (and vice versa). There was little indication of extensive bias
      towards selective silencing of a particular genome copy. Expression of some of
      the silenced homoeoalleles was restored in certain aneuploid lines and varieties,
      and these displayed a significant degree of genetic variation for the silencing
      of a given homoeoallele. We propose that a substantial proportion of this
      phenomenon is effected by an epigenetic mechanism, and suggest that this form of
      genetic variation may be a significant player in the determination of phenotypic
      diversity in breeding populations.

PMID- 16899085
TI  - Molecular dissection of the Munc18c/syntaxin4 interaction: implications for
      regulation of membrane trafficking.
AB  - Sec1p/Munc18 (SM) proteins are believed to play an integral role in vesicle
      transport through their interaction with SNAREs. Different SM proteins have been
      shown to interact with SNAREs via different mechanisms, leading to the conclusion
      that their function has diverged. To further explore this notion, in this study,
      we have examined the molecular interactions between Munc18c and its cognate
      SNAREs as these molecules are ubiquitously expressed in mammals and likely
      regulate a universal plasma membrane trafficking step. Thus, Munc18c binds to
      monomeric syntaxin4 and the N-terminal 29 amino acids of syntaxin4 are necessary
      for this interaction. We identified key residues in Munc18c and syntaxin4 that
      determine the N-terminal interaction and that are consistent with the N-terminal
      binding mode of yeast proteins Sly1p and Sed5p. In addition, Munc18c binds to the
      syntaxin4/SNAP23/VAMP2 SNARE complex. Pre-assembly of the syntaxin4/Munc18c dimer
      accelerates the formation of SNARE complex compared to assembly with syntaxin4
      alone. These data suggest that Munc18c interacts with its cognate SNAREs in a
      manner that resembles the yeast proteins Sly1p and Sed5p rather than the
      mammalian neuronal proteins Munc18a and syntaxin1a. The Munc18c-SNARE
      interactions described here imply that Munc18c could play a positive regulatory
      role in SNARE assembly.

PMID- 16899086
TI  - Multilayer interactions determine the Golgi localization of GRIP golgins.
AB  - Golgin-97, RanBP2alpha, Imh1p and p230/golgin-245 (GRIP) domain golgins are
      targeted to the Golgi membrane through their GRIP domains. By analyzing more than
      30 mutants of golgin-97 and golgin-245 GRIP domains for their properties of
      dimerization, interaction with ARF like protein 1 (Arl1)-GTP and Golgi targeting,
      we found hierarchically organized three-tier interactions governing the Golgi
      targeting of GRIP domain golgins. GRIP domain self-dimerization is necessary for
      bivalent interaction with Arl1-GTP. Unexpectedly, however, these two interactions
      are not sufficient for Golgi targeting, as a third group of residues, including
      positive-charged arginine between alpha1 and alpha2 and hydrophobic residues C
      terminal to the GRIP domain, turn out to be essential. Surface plasmon resonance
      analysis indicates that GRIP domain interacts directly with membrane lipid,
      partially through the third group of residues such as W744 of golgin-97. This
      third tier of interaction with the membrane could be mediated by non-specific
      hydrophobic and electrostatic forces.

PMID- 16899088
TI  - Distinct clathrin-coated pits sort different G protein-coupled receptor cargo.
AB  - Upon activation, many G protein-coupled receptors (GPCRs) internalize by clathrin
      mediated endocytosis and are subsequently sorted to undergo recycling or
      lysosomal degradation. Here we observe that sorting can take place much earlier
      than previously thought, by entry of different GPCRs into distinct populations of
      clathrin-coated pit (CCP). These distinct populations were revealed by analysis
      of two purinergic GPCRs, P2Y(1) and P2Y(12), which enter two populations of CCPs
      in a mutually exclusive manner. The mechanisms underlying early GPCR sorting
      involve differential kinase-dependent processes because internalization of
      P2Y(12) is mediated by GPCR kinases (GRKs) and arrestin, whereas P2Y(1)
      internalization is GRK- and arrestin-independent but requires protein kinase C.
      Importantly, the beta(2) adrenoceptor which also internalizes in a GRK-dependent
      manner also traffics exclusively to P2Y(12)-containing CCPs. Our data therefore
      reveal distinct populations of CCPs that sort GPCR cargo at the plasma membrane
      using different kinase-dependent mechanisms.

PMID- 16899087
TI  - Vaccinia-virus-induced cellular contractility facilitates the subcellular
      localization of the viral replication sites.
AB  - Poxviruses, such as vaccinia virus (VV), replicate their DNA in endoplasmic
      reticulum-enclosed cytoplasmic sites. Here, we compare the dynamics of the VV
      replication sites with those of the attenuated strain, modified VV Ankara (MVA).
      By live-cell imaging, small, early replication sites of both viruses undergo
      motility typical of microtubule (MT)-motor-mediated movement. Over time, growing
      replication sites of VV collect around the nucleus in a MT-dependent fashion,
      whereas those of MVA remain mostly scattered in the cytoplasm. Surprisingly,
      blocking the dynein function does not impair the perinuclear accumulation of
      large VV replication sites. Live-cell imaging demonstrates that in contrast to
      small replication sites, large sites do not display MT-motor-mediated motility.
      Instead, VV infection induces cellular contractility that facilitates the
      collection of growing replication sites around the nucleus. In a subset of cells
      (30-40%), this VV-induced contractility is alternated by phases of directed cell
      migration, suggesting that the two processes may be linked. The MVA-infected
      cells do not display contractility or cell migration, supporting the idea that
      these cellular activities facilitate the efficient accumulation of the VV
      replication sites around the nucleus. We propose that the recently described
      cytoskeletal rearrangements induced by VV are a prerequisite for the observed
      cell contractility and migration activities that apparently contribute to the
      organization of the complex cytoplasmic life cycle of VV.

PMID- 16899089
TI  - Dynamics and cardiac arrhythmias.
AB  - Cardiac arrhythmias, characterized by single or multiple reentrant circuits,
      represent a dynamic phenomenon in an excitable medium. In this review, we provide
      a brief overview of how cardiac action potential duration restitution, conduction
      velocity restitution, and intracellular calcium cycling regulate the dynamics of
      action potential excitation and wave propagation in relation to the genesis and
      maintenance of cardiac arrhythmias.

PMID- 16899090
TI  - A pacemaker infection that was apparently localized to the atrial set screw.

PMID- 16899092
TI  - From observational studies to randomized trials: asking the right question at the
      right time.

PMID- 16899093
TI  - Spurious associations in oral epidemiological research: the case of dental
      flossing and obesity.
AB  - BACKGROUND: Individuals with increased oral health awareness may also have
      increased general health awareness, and vice versa. Such associations between
      oral and general health awareness has the potential to induce spurious
      associations in oral epidemiological research. OBJECTIVE: To assess the extent to
      which oral self-care patterns and general health awareness are confounded, we
      investigated the association between flossing and obesity, two lifestyle factors
      that are unlikely to be causally related. METHODS: A cross-sectional study of
      1497 individuals presenting for an initial periodontal exam by the specialist.
      Self-reported flossing behaviors and body mass index (BMI) categories were
      related using logistic regression models. RESULTS: After adjustment for
      confounding variables, lack of daily flossing was associated in a dose-dependent
      way with morbid obesity (odds ratio (OR), 20.3; 95% confidence interval (CI), 2.7
      154.0), obesity (OR, 2.1; 95% CI, 1.5-2.9), and being overweight (OR, 1.7; 95%
      CI, 1.3-2.2). When restricting to never smokers, a significant relationship
      between obesity and lack of flossing remained. CONCLUSION: The strong
      associations between two causally unrelated oral and general lifestyle
      characteristics indicate that simplistic epidemiologic methodology is unlikely to
      provide insights into causal mechanisms of oral diseases or oral-systemic
      relationships.

PMID- 16899094
TI  - The short vitamin D receptor is associated with increased risk for generalized
      aggressive periodontitis.
AB  - BACKGROUND: Generalized aggressive periodontitis (GAP) exhibits severe
      inflammation and alveolar bone loss. Vitamin D receptor (VDR) regulates both bone
      metabolism and inflammation-related genes, and its polymorphisms and haplotypes
      may affect the functional activity of the VDR protein in GAP. OBJECTIVE: We
      analysed the genetic effect of VDR start codon, intron, and exon polymorphisms,
      and their haplotypes on the development of GAP. MATERIALS AND METHODS: The VDR
      start codon 27823C > T (rs2228570, FokI), intron 8 60890G > A (rs154410, BsmI),
      and exon 9 61968T > C (rs731236, TaqI) polymorphisms were determined by using the
      polymerase chain reaction-restriction fragment length polymorphism analysis among
      93 GAP patients and 143 healthy controls. RESULTS: The VDR start codon 27823*C/*C
      genotype was associated with an increased risk for GAP [odds ratio (OR) = 1.83, p
      = 0.028], but the intron 8 60880G > A and exon 9 61968T > C polymorphisms were
      not associated with GAP. The VDR haplotype homozygote ht1(C-G-T) carrying 27823*C
      allele was associated with a 1.8-fold increased risk of GAP (OR = 1.84, p =
      0.030). CONCLUSION: These results demonstrate that the short VDR (27823*C/*C)
      protein may influence GAP susceptibility.

PMID- 16899095
TI  - NADPH oxidase (CYBA) and FcgammaR polymorphisms as risk factors for aggressive
      periodontitis: a case-control association study.
AB  - INTRODUCTION: Neutrophils (PMN) in aggressive periodontitis (AgP) patients have
      been reported to be hyperactive especially with regards to superoxide production.
      Polymorphisms in genes influencing PMN function have been proposed as candidate
      risk factors for AgP. The aim of this study was to test the association of
      specific gene polymorphisms affecting PMN functions with AgP. MATERIALS AND
      METHODS: Two hundred and twenty-four patients with confirmed diagnosis of AgP and
      231 subjects with healthy periodontium took part in the study. A blood sample was
      collected from subjects and genotypes for p22phox (CYBA) NADPH oxidase, FP,
      Fcalpha and Fcgamma receptors were analysed in a blind fashion. RESULTS: The
      C242T p22phox NADPH oxidase T allele was significantly associated with AgP in a
      multiple logistic regression model adjusting for confounders, and this was
      observed for all subjects [p = 0.002, odds ratio (OR) = 1.87, 95% confidence
      interval (CI) = 1.27-2.83] and Caucasians (p = 0.009, OR=2.07, 95% CI = 1.20
      3.59). Concomitant presence of C242T p22phox NADPH oxidase T allele and
      FcgammaRIIIb NA1 homozygosity was associated with the generalized AgP phenotype
      in Caucasians (p = 0.001, OR = 30.35, 95% CI = 3.81-241.97). CONCLUSIONS: C242T
      p22phox NADPH oxidase and FcgammaR polymorphisms may predispose to AgP through a
      modulation of neutrophil superoxide production.

PMID- 16899097
TI  - Smokeless tobacco (snuff) use and periodontal bone loss.
AB  - OBJECTIVE: The aim of the present cross-sectional study was to investigate a
      possible association between the use of Swedish moist snuff and periodontal bone
      loss. MATERIAL AND METHODS: The study was carried out on 84 apparently healthy
      men in the age range 26-54 years, 25 current snuff users, 21 former snuff users,
      and 38 never-users. The periodontal bone height was evaluated from bitewing
      radiographs measuring the distance from the cement-enamel junction (CEJ) to the
      periodontal bone crest (PBC) at pre-molars and molars in each quadrant of the
      dentition. RESULTS: The mean (95% confidence interval (95% CI)) CEJ-PBC distance
      was 1.00 (0.87-1.13), 1.12 (0.97-1.26), and 1.06 (0.95-1.16) mm for current
      users, former users, and never-users, respectively. The association between snuff
      use and bone height level controlling for age was not statistically significant
      (anovaF = 0.3, p > 0.05). There was, further, no statistically significant
      difference between light and heavy exposure users controlling for age (anovaF =
      1.0, p > 0.05). CONCLUSION: Our observations suggest that the use of Swedish
      moist snuff is not associated with periodontal bone loss.

PMID- 16899096
TI  - Java project on periodontal diseases. The natural development of periodontitis:
      risk factors, risk predictors and risk determinants.
AB  - OBJECTIVE: To identify risk factors, risk predictors and risk determinants for
      onset and progression of periodontitis. MATERIAL AND METHODS: For this
      longitudinal, prospective study all subjects in the age range 15-25 years living
      in a village of approximately 2000 inhabitants at a tea estate on Western Java,
      Indonesia, were selected. Baseline examination was carried out in 1987 and follow
      up examinations in 1994 and 2002. In 2002, 128 subjects could be retrieved from
      the original group of 255. Baseline examination included evaluation of plaque,
      bleeding on probing, calculus, pocket depth, attachment loss and presence of
      Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Prevotella
      intermedia, spirochetes and motile microorganisms. RESULTS: The mean attachment
      loss increased from 0.33 mm in 1987 to 0.72 mm in 1994 and 1.97 mm in 2002.
      Analysis identified the amount of subgingival calculus and subgingival presence
      of A. actinomycetemcomitans as risk factors, and age as a risk determinant, for
      the onset of disease. Regarding disease progression, the number of sites with a
      probing depth > or = 5 mm and the number of sites with recession were identified
      as risk predictors and male gender as a risk determinant. CONCLUSION: Screening
      of these parameters early in life could be helpful in the prevention of onset and
      progression of periodontal diseases.

PMID- 16899098
TI  - A cross-over study on the effect of various therapeutic approaches to morning
      breath odour.
AB  - OBJECTIVE: The aim of this study was to investigate the effect of tongue scraping
      and inter-dental flossing on morning bad breath in periodontally healthy
      subjects. METHODS: A four-step blind, cross-over study was conducted in 19
      volunteers, divided into four groups: Group I: tooth brushing; Group II: tooth
      brushing and inter-dental flossing; Group III: tooth brushing and tongue
      scraping; and Group IV: tooth brushing, inter-dental flossing and tongue
      scraping. The volunteers performed these oral hygiene procedures three times a
      day for 7 days. Seven-day wash-out intervals were observed. Morning mouth breath
      was assessed organoleptically and by volatile sulphur compound concentrations.
      RESULTS: The highest mean organoleptic and volatile sulphur compound measurement
      values were found in the treatment groups in which tongue scraping was not
      performed and there were statistical differences between the two groups (p <
      0.05). In the organoleptic evaluation (p > 0.05), inter-dental flossing did not
      show any statistical improvement in the effect of tongue hygiene on morning bad
      breath, but it significantly reduced the concentration of volatile sulphur
      compounds (p < 0.05). CONCLUSION: The findings suggest that tongue scraping
      appears to be the most important hygienic procedure to reduce morning bad breath
      in periodontally healthy subjects.

PMID- 16899099
TI  - Effect of two new chlorhexidine mouthrinses on the development of dental plaque,
      gingivitis, and discolouration. A randomized, investigator-blind, placebo
      controlled, 3-week experimental gingivitis study.
AB  - OBJECTIVE: The aim of this experimental gingivitis study was to assess the
      efficacy and safety of two new chlorhexidine (CHX) mouthrinses. MATERIAL AND
      METHODS: Ninety volunteers participated in this investigator-blind, randomized,
      clinical-controlled trial in parallel groups. During the treatment period, no
      oral hygiene measures except rinsing with non-alcoholic 0.2% CHX or 0.2%
      CHX/0.055% sodium fluoride mouthrinses, a positive control, or a negative control
      were permitted. The primary parameter was the gingival index; the secondary
      parameters were plaque index, discolouration index, and bleeding on probing.
      Clinical examinations were conducted 14 days before the start of the study, at
      baseline, and after 7, 14, and 21 days. The two sample t-test, anova, and ancova
      were used for the statistical analysis. RESULTS: No difference in efficacy was
      found between the two new CHX formulations and the positive control. On day 21,
      statistically significantly less gingival inflammation and plaque accumulation
      compared with placebo were observed. Besides discolouration and taste
      irritations, no adverse events were recorded. CONCLUSION: The two new CHX
      mouthrinses were able to inhibit plaque re-growth and gingivitis. Neither the
      omission of alcohol nor the supplementation with sodium fluoride had weakened the
      clinical efficacy of CHX with respect to the analysed clinical parameters.

PMID- 16899100
TI  - Efficiency of the Vector -system compared with conventional subgingival
      debridement in vitro and in vivo.
AB  - OBJECTIVE: To assess the efficacy of the novel ultrasonic Vector -system system
      for subgingival debridement and to compare the results with conventional
      periodontal instrumentation in vitro and in vivo. MATERIAL AND METHODS: Forty
      extracted human teeth were treated in vitro: Vector -system with polishing (VP)
      and abrasive fluid (VA), conventional ultrasonic system (U) and hand instrument
      (H). At intervals of 40 s, calculus removal was assessed using a 3D laser
      scanning device. Eight single-rooted teeth were treated in vivo with the Vector 
      system or hand instruments. Subgingival plaque samples were obtained for
      microbiological evaluation. After extraction, residual calculus was assessed by
      means of digitized planimetry. RESULTS: In vitro efficiency of hand instruments
      was statistically higher compared with the conventional ultrasonic system (p <
      0.05) and the Vector -system with no difference between U and VA (p > 0.05) and
      VA and VP (p > 0.05). Residual calculus following in vivo instrumentation was not
      different in the Vector and the hand instrument group (p > 0.05) but treatment
      time with the Vector -system was statistically higher (p < 0.05). A similar
      reduction of periopathogenic bacteria could be observed in both groups.
      CONCLUSION: Using the Vector -system, root surfaces can be debrided as thoroughly
      as with conventional instruments. However, treatment is more time consuming than
      conventional debridement.

PMID- 16899101
TI  - A randomized clinical multicentre trial comparing enamel matrix derivative and
      membrane treatment of buccal class II furcation involvement in mandibular molars.
      Part III: patient factors and treatment outcome.
AB  - OBJECTIVE: Evaluation of effects of patient factors on the outcome of
      regenerative treatment of buccal mandibular class II furcation defects. MATERIAL
      AND METHODS: Fifty-one patients were recruited. In the intention-to-treat
      population 21 patients were allocated into the sequence left treatment with
      enamel matrix protein derivative (EMD) and right guided tissue regeneration (GTR)
      and 27 in the sequence left GTR and right EMD. Evaluated patient factors were:
      smoking, age, gender, hypertension and oral hygiene status. Outcome parameters
      included change of: (a) horizontal depth of the defect at the deepest point (b)
      distance from the fornix of the furcation to bone crest of the defect, (c)
      distance from stent to the bottom of the defect, (d) pocket depth and (e)
      attachment level at the middle of the furcation. RESULTS: In patients 54 years of
      age and older, in males, in non-smokers and in patients with "poor" hygiene EMD
      treated sites showed a significant higher mean reduction of the parameters d
      (age), b (gender, hygiene) a (smoking, hygiene) when compared with sites treated
      with GTR. CONCLUSIONS: These data provided an indication of a possible effect of
      patient factors on the outcome of regenerative treatment of buccal mandibular
      class II furcation defects.

PMID- 16899102
TI  - Influence of different treatment approaches on non-submerged and submerged
      healing of ligature induced peri-implantitis lesions: an experimental study in
      dogs.
AB  - OBJECTIVE: [corrected] The aim of the present study was to evaluate non-submerged
      and submerged healing of ligature induced peri-implantitis in dogs. MATERIAL AND
      METHODS: Peri-implantitis was induced by ligature placement in five beagle dogs
      (n = 30 implants). The defects were randomly and equally allocated in a split
      mouth design to either closed treatment + non-submerged healing (CNS), or open
      treatment + submerged healing (OS) using an Er:YAG laser (ERL), an ultrasonic
      device (VUS), or plastic curettes + local application of metronidazole gel (PCM),
      respectively. The animals were sacrificed after 3 months. Clinical, radiological
      and histological (e.g. new bone-to-implant contact (BIC)) parameters were
      assessed. RESULTS: All treatment procedures resulted in statistically significant
      improvements of all clinical parameters at both CNS and OS implants. Radiological
      improvements were merely observed at OS implants. Histomorphometrical analysis
      revealed that all CNS implants exhibited comparable low amounts of new BIC (1.0
      1.2%), while mean BIC was statistically significant higher in the respective OS
      groups [ERL (44.8%), PCM (14.8%), VUS (8.7%)]. CONCLUSION: Within the limits of
      the present study, it was concluded that (i) OS improved the outcome of treatment
      in comparison with CNS and (ii) ERL seemed to be more suitable to promote re
      osseointegration than PCM and VUS.

PMID- 16899104
TI  - Symposium Mammographicum 2006, Bournemouth, United Kingdom, 9-11 July 2006.
      Abstracts.

PMID- 16899103
TI  - The structure of periodontal tissues formed following guided tissue regeneration
      therapy of intra-bony defects in the monkey.
AB  - OBJECTIVE: To describe the periodontal tissues formed following guided tissue
      regeneration (GTR) therapy of intra-bony defects (IBD). METHODS: Eight adult
      Macaca fascicularis monkeys were used. Proximal IBD were created at the
      mandibular second pre-molars and second molars. After 3 months, GTR surgery was
      performed. The animals were euthanized at 6 months and 2 years after surgery.
      Block biopsies were harvested, and prepared for histological analysis. RESULTS:
      At 6 months the defect had healed with new cementum (NC), periodontal ligament
      (PDL) and bone. The NC seemed to be firmly anchored to the dentin. Supra
      crestally, the NC consisted of a 10 microm thick layer of acellular extrinsic
      fibre cementum (AEFC). Sub-crestally, the NC was considerably thicker and
      consisted of an inner layer of AEFC and an outer thicker layer of cellular mixed
      fibre cementum (CMFC). The extrinsic fibre density amounted to about 10 fibres
      per 100 microm. The PDL was wider than the pristine PDL and widened in coronal
      direction. After 2 years of healing, the thickness of the NC in the sub-crestal
      compartment had increased by about 20 microm and the fibre density had increased
      by about 50%. CONCLUSION: After 2 years of healing the structure of the
      regenerated tissues resembled that of pristine periodontal tissues.

PMID- 16899105
TI  - Expanding the frontiers of therapy.

PMID- 16899106
TI  - Interleukin-6: discovery of a pleiotropic cytokine.
AB  - In the late 1960s, the essential role played by T cells in antibody production
      was reported. This led to our hypothesis that certain molecules would have to be
      released from T cells to effect the stimulation of B cells. This hypothesis was
      shown to be true. There were certain factors present in the culture supernatant
      of T cells that induced proliferation and differentiation of B cells. The factor
      that induced B cells to produce immunoglobulins was initially named B cell
      stimulatory factor-2. The cDNA encoding the human B cell stimulatory factor-2 was
      cloned in 1986. At the same time, IFN-beta2 and a 26 kDa protein in the
      fibroblasts were independently cloned and found to be identical to B cell
      stimulatory factor-2. Later, a hybridoma/plasmacytoma growth factor and a
      hepatocyte stimulating factor were also proven to be the same molecule as B cell
      stimulatory factor-2. Various names were used for this single molecule because of
      its multiple biological activities, but these have all been unified and the
      molecule is now known as IL-6. Since the discovery of IL-6, rapid progress has
      been made in our understanding of IL-6 activities, the IL-6 receptor system and
      the IL-6 signal transduction mechanism. More importantly, it has been shown to be
      involved in a number of diseases such as rheumatoid arthritis and Castleman's
      disease. When taking into account all the accumulated basic research on the
      various aspects of this molecule, it appeared that blocking the activity of IL-6
      was a feasible, new therapeutic approach for chronic inflammatory diseases.

PMID- 16899107
TI  - Interleukin-6 and chronic inflammation.
AB  - Interleukin (IL)-6 is produced at the site of inflammation and plays a key role
      in the acute phase response as defined by a variety of clinical and biological
      features such as the production of acute phase proteins. IL-6 in combination with
      its soluble receptor sIL-6Ralpha, dictates the transition from acute to chonic
      inflammation by changing the nature of leucocyte infiltrate (from
      polymorphonuclear neutrophils to monocyte/macrophages). In addition, IL-6 exerts
      stimulatory effects on T- and B-cells, thus favoring chronic inflammatory
      responses. Strategies targeting IL-6 and IL-6 signaling led to effective
      prevention and treatment of models of rheumatoid arthritis and other chronic
      inflammatory diseases.

PMID- 16899108
TI  - Interleukin-6 and rheumatic diseases.
AB  - IL-6 is a pleiotropic cytokine involved in both the initiation and the
      maintenance of the inflammatory and immunologic responses in certain autoimmune
      diseases. Blocking of these two complementary functions of IL-6 may confer
      additive, or even unique, benefits to the patient. The levels of both IL-6 and
      its soluble receptor (sIL-6Ralpha) are elevated to various degrees in many
      rheumatic diseases. IL-6 blockade has been shown to be beneficial both in
      experimental models and in human disease, and inhibition of IL-6 signaling with a
      molecule such as tocilizumab could prevent or reverse some of the complications
      typically associated with rheumatic diseases.

PMID- 16899109
TI  - Interleukin-6: a new therapeutic target.
AB  - The therapeutic success of biological agents, especially the tumour necrosis
      factor (TNF) inhibitors, has opened a new chapter in the book of therapies for
      rheumatoid arthritis. Nevertheless, more than 50% of patients may not respond by
      > 50% improvement. New compounds have recently entered the treatment arena. One
      of these is rituximab, which depletes B cells, and another, abatacept, interferes
      with T-cell co-stimulation. However, although these agents may be effective in a
      number of patients who fail to respond to TNF blockade, they only rarely induce
      remission and overall 50% response rates do not exceed those with the TNF
      inhibitors. Among the major proinflammatory cytokines, IL-6 plays a pleiotropic
      role both in terms of activating the inflammatory response and
      osteoclastogenesis. Here, we review recent phase II trials of tocilizumab, a
      humanized anti-IL-6 receptor antibody that achieves a significant therapeutic
      response rate.

PMID- 16899110
TI  - Surveillance recommendations based on an exploratory analysis of respiratory
      syncytial virus reports derived from the European Influenza Surveillance System.
AB  - BACKGROUND: Respiratory syncytial virus (RSV) is an important pathogen that can
      cause severe illness in infants and young children. In this study, we assessed
      whether data on RSV collected by the European Influenza Surveillance Scheme
      (EISS) could be used to build an RSV surveillance system in Europe. METHODS:
      Influenza and RSV data for the 2002-2003 winter season were analysed for England,
      France, the Netherlands and Scotland. Data from sentinel physician networks and
      other sources, mainly hospitals, were collected. Respiratory specimens were
      tested for influenza and RSV mainly by virus culture and polymerase chain
      reaction amplification. RESULTS: Data on RSV were entered timely into the EISS
      database. RSV contributed noticeably to influenza-like illness: in England
      sentinel RSV detections were common in all age groups, but particularly in young
      children with 20 (40.8%) of the total number of sentinel swabs testing positive
      for RSV. Scotland and France also reported the highest percentages of RSV
      detections in the 0-4 year age group, respectively 10.3% (N = 29) and 12.2% (N =
      426). In the Netherlands, RSV was detected in one person aged over 65 years.
      CONCLUSION: We recommend that respiratory specimens collected in influenza
      surveillance are also tested systematically for RSV and emphasize the use of both
      community derived data and data from hospitals for RSV surveillance. RSV data
      from the EISS have been entered in a timely manner and we consider that the EISS
      model can be used to develop an RSV surveillance system equivalent to the
      influenza surveillance in Europe.

PMID- 16899111
TI  - Annotation of novel neuropeptide precursors in the migratory locust based on
      transcript screening of a public EST database and mass spectrometry.
AB  - BACKGROUND: For holometabolous insects there has been an explosion of proteomic
      and peptidomic information thanks to large genome sequencing projects.
      Heterometabolous insects, although comprising many important species, have been
      far less studied. The migratory locust Locusta migratoria, a heterometabolous
      insect, is one of the most infamous agricultural pests. They undergo a well-known
      and profound phase transition from the relatively harmless solitary form to a
      ferocious gregarious form. The underlying regulatory mechanisms of this phase
      transition are not fully understood, but it is undoubtedly that neuropeptides are
      involved. However, neuropeptide research in locusts is hampered by the absence of
      genomic information. RESULTS: Recently, EST (Expressed Sequence Tag) databases
      from Locusta migratoria were constructed. Using bioinformatical tools, we
      searched these EST databases specifically for neuropeptide precursors. Based on
      known locust neuropeptide sequences, we confirmed the sequence of several
      previously identified neuropeptide precursors (i.e. pacifastin-related peptides),
      which consolidated our method. In addition, we found two novel neuroparsin
      precursors and annotated the hitherto unknown tachykinin precursor. Besides one
      of the known tachykinin peptides, this EST contained an additional tachykinin
      like sequence. Using neuropeptide precursors from Drosophila melanogaster as a
      query, we succeeded in annotating the Locusta neuropeptide F, allatostatin-C and
      ecdysis-triggering hormone precursor, which until now had not been identified in
      locusts or in any other heterometabolous insect. For the tachykinin precursor,
      the ecdysis-triggering hormone precursor and the allatostatin-C precursor,
      translation of the predicted neuropeptides in neural tissues was confirmed with
      mass spectrometric techniques. CONCLUSION: In this study we describe the
      annotation of 6 novel neuropeptide precursors and the neuropeptides they encode
      from the migratory locust, Locusta migratoria. By combining the manual annotation
      of neuropeptides with experimental evidence provided by mass spectrometry, we
      demonstrate that the genes are not only transcribed but also translated into
      precursor proteins. In addition, we show which neuropeptides are cleaved from
      these precursor proteins and how they are post-translationally modified.

PMID- 16899112
TI  - SNFing HIV transcription.
AB  - The SWI/SNF chromatin remodeling complex is an essential regulator of
      transcription of cellular genes. HIV-1 infection induces exit of a core component
      of SWI/SNF, Ini1, into the cytoplasm and its association with the viral pre
      integration complex. Several recent papers published in EMBO Journal, Journal of
      Biological Chemistry, and Retrovirology provide new information regarding
      possible functions of Ini1 and SWI/SNF in HIV life cycle. It appears that Ini1
      has an inhibitory effect on pre-integration steps of HIV replication, but also
      contributes to stimulation of Tat-mediated transcription. This stimulation
      involves displacement of the nucleosome positioned at the HIV promoter.

PMID- 16899114
TI  - Traditional use of medicinal plants by the Jaintia tribes in North Cachar Hills
      district of Assam, northeast India.
AB  - The study of ethnobotany relating to any tribe is in itself a very intricate or
      convoluted process. This paper documents the traditional knowledge of medicinal
      plants that are in use by the indigenous Jaintia tribes residing in few isolated
      pockets of northeast India. The present study was done through structured
      questionnaires in consultations with the tribal practitioners and has resulted in
      the documentation of 39 medicinal plant species belonging to 27 families and 35
      genera. For curing diverse form of ailments, the use of aboveground plant parts
      was higher (76.59%) than the underground plant parts (23.41%). Of the aboveground
      plant parts, leaf was used in the majority of cases (23 species), followed by
      fruit (4). Different underground plant forms such as root, tuber, rhizome, bulb
      and pseudo-bulb were also found to be in use by the Jaintia tribe as a medicine.
      Altogether, 30 types of ailments have been reported to be cured by using these 39
      medicinal plant species. The study thus underlines the potentials of the
      ethnobotanical research and the need for the documentation of traditional
      ecological knowledge pertaining to the medicinal plant utilization for the
      greater benefit of mankind.

PMID- 16899113
TI  - Down-regulation of c-Myc following MEK/ERK inhibition halts the expression of
      malignant phenotype in rhabdomyosarcoma and in non muscle-derived human tumors.
AB  - BACKGROUND: Expression of c-myc proto-oncogene is inappropriate in a wide range
      of human tumors, and is a downstream target of Ras/Raf/ERK pathway, which
      promotes c-Myc stability by enhancing c-Myc expression and activity. The aim of
      this study was to investigate whether the oncogenic phenotype in the human muscle
      derived Rhabdomyosarcoma (RD) cell line and in non muscle-derived human tumor
      cell lines (SW403, IGR39 and PC3) can be blocked by disrupting the c-Myc pathway
      either by means of pharmacological MEK/ERK inhibition or by direct inactivation
      of the c-Myc protein. RESULTS: We demonstrate that, in all the tumor cell lines
      used, the MEK/ERK inhibitor U0126 rapidly induces c-Myc de-phosphorylation, which
      is followed by a marked reduction in its expression level, by inhibition of
      proliferation and by reversion of anchorage-independent growth. These data
      suggest that the targeting of pathways controlling c-Myc expression or stability
      reverses deregulated growth of different tumor-derived cell lines. Indeed, in RD
      cells, we found a marked down-regulation of cyclins E2, A and B and CDK2, all of
      which are known to be targets of c-Myc. Moreover, ectopic MadMyc chimera, a c-Myc
      function antagonist, causes dramatic growth arrest, CDK and cyclin modulation as
      well as inhibition of anchorage-independent growth in RD cells, as occurs in
      U0126-treated cells. In particular, we found that the mere inhibition of c-Myc by
      MadMyc chimera rescues the myogenic program, MHC expression and the acquisition
      of the myogenic-like phenotype in RD cells. CONCLUSION: Our data provide evidence
      of the key role played by the MEK/ERK pathway in the growth arrest and
      transformation phenotype of Rhabdomyosarcoma and of non muscle-derived tumor cell
      lines. In fact, MEK/ERK inhibitor, U0126, induces growth arrest, anchorage
      dependent growth of these cell lines. In addition, the results of this study
      demonstrate that the direct inactivation of c-Myc by Mad/Myc chimera rescues
      myogenic program and leads to the reversal of the Rhabdomyosarcoma phenotype. In
      conclusion these data strongly suggest that the targeting of c-Myc by means of
      the MEK inhibitor can be tested as a promising strategy in anti-cancer therapy.

PMID- 16899115
TI  - Mammary Paget's disease occurring after mastectomy.
AB  - BACKGROUND: Mammary Paget's disease and extramammary Paget's disease are
      neoplastic conditions, in which there is intraepithelial (usually intraepidermal)
      infiltration by neoplastic cells showing glandular differentiation. Mammary
      Paget's disease occurs exclusively on the nipple/areola complex from where it may
      spread to the surrounding skin. CASE PRESENTATION: We here describe a case of
      Paget's disease occurring on the thoracic wall site of a previous simple
      mastectomy, and also briefly summarise the most important aspects leading to a
      diagnosis of mammary Paget's disease. CONCLUSION: To the best of our knowledge,
      this is the first reported case of mammary Paget's disease occurring after
      mastectomy. The absence of the nipple/areola complex obviously raised some
      questions concerning whether it was mammary or extra-mammary Paget's disease, and
      how it could occur in the absence of the nipple/areola complex.

PMID- 16899116
TI  - Numb chin syndrome--a reflection of systemic malignancy.
AB  - BACKGROUND: Numb chin is an uncommon underappreciated though well documented
      neurological manifestation of metastatic malignancy. CASE PRESENTATION: A 50-year
      old patient presented with right numb chin for few days. No dental cause was
      found. He later developed generalized vague symptoms. In few weeks his liver and
      renal functions deteriorated. Blood picture showed leucoerythroblastic picture.
      CT scan and bone marrow biopsy done at this stage revealed underlying high grade
      lymphoblastic lymphoma. He went into multiorgan failure, requiring ventilatory
      support and death within a short period. CONCLUSION: Numb Chin is a syndrome
      which initially presents with unilateral numbness or orofacial pain in the
      distribution of the inferior alveolar nerve and its branches with an underlying
      systemic malignancy. We emphasise that physicians and dentists should consider
      metastatic cancer in any patient who presents with chin or jaw numbness where no
      other obvious cause for their complaint is found.

PMID- 16899117
TI  - Frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17).
AB  - Frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) is an
      autosomal dominant neurodegenerative disorder, which has three cardinal features:
      behavioral and personality changes, cognitive impairment, and motor symptoms.
      FTDP-17 was defined during the International Consensus Conference in Ann Arbor,
      Michigan, in 1996. The prevalence and incidence remain unknown but FTDP-17 is an
      extremely rare condition. It is caused by mutations in the tau gene, which
      encodes a microtubule-binding protein. Over 100 families with 38 different
      mutations in the tau gene have been identified worldwide. The phenotype of FTDP
      17 varies not only between families carrying different mutations but also between
      and within families carrying the same mutations. The pathogenetic mechanisms
      underlying the disorder are thought to be related to the altered proportion of
      tau isoforms or to the ability of tau to bind microtubules and to promote
      microtubule assembly. Definitive diagnosis of FTDP-17 requires a combination of
      characteristic clinical and pathological features and molecular genetic analysis.
      Genetic counseling should be offered to affected and at-risk individuals; for
      most subtypes, penetrance is incomplete. Currently, treatment for FTDP-17 is only
      symptomatic and supportive. The prognosis and rate of the disease's progression
      vary considerably among individual patients and genetic kindreds, ranging from
      life expectancies of several months to several years, and, in exceptional cases,
      as long as two decades.

PMID- 16899118
TI  - Determinants of short and long term functional recovery after hospitalization for
      community-acquired pneumonia in the elderly: role of inflammatory markers.
AB  - BACKGROUND: Hospitalization for older patients with community-acquired pneumonia
      (CAP) is associated with functional decline. Little is know about the
      relationship between inflammatory markers and determinants of functional status
      in this population. The aim of the study is to investigate the association
      between tumor necrosis factor (TNF)-alpha, C-reactive protein (CRP) and
      Activities of Daily Living, and to identify risk factors associated with one year
      mortality or hospital readmission. METHODS: 301 consecutive patients hospitalized
      for CAP (mean age 73.9 +/- 5.3 years) in a University affiliated hospital over 18
      month period were included. All patients were evaluated on admission to identify
      baseline demographic, microbiological, cognitive and functional characteristics.
      Serum levels for TNF-alpha and CRP were collected at the same time. Reassessment
      of functional status at discharge, and monthly thereafter till 3 months post
      discharge was obtained and compared with preadmission level to document loss or
      recovery of functionality. Outcome was assessed by the composite endpoint of
      hospital readmission or death from any cause up to one year post hospital
      discharge. RESULTS: 36% of patients developed functional decline at discharge and
      11% had persistent functional impairment at 3 months. Serum TNF-alpha (odds ratio
      [OR] 1.12, 95% CI 1.08-1.15; p < 0.001) and the Charlson Index (OR = 1.39, 95% CI
      1.14 to 1.71; p = 0.001) but not age, CRP, or cognitive status were independently
      associated with loss of functionality at the time of hospital discharge. Lack of
      recovery in functional status at 3 months was associated with impaired cognitive
      ability and preadmission comorbidities. In Cox regression analysis, persistent
      functional impairment at 3 months, impaired cognitive function, and the Charlson
      Index were highly predictive of one year hospital readmission or death.
      CONCLUSION: Serum TNF-alpha levels can be useful in determining patients at risk
      for functional impairment following hospitalization from CAP. Old patients with
      impaired cognitive function and preexisting comorbidities who exhibit delay in
      functional recovery at 3 months post discharge may be at high risk for hospital
      readmission and death. With the scarcity of resources, a future risk
      stratification system based on these findings might be proven helpful to target
      older patients who are likely to benefit from interventional strategies.

PMID- 16899119
TI  - Role of chromosome stability and telomere length in the production of viable cell
      lines for somatic cell nuclear transfer.
AB  - BACKGROUND: Somatic cell nuclear transfer (SCNT) provides an appealing
      alternative for the preservation of genetic material in non-domestic and
      endangered species. An important prerequisite for successful SCNT is the
      availability of good quality donor cells, as normal embryo development is
      dependent upon proper reprogramming of the donor genome so that embryonic genes
      can be appropriately expressed. The characteristics of donor cell lines and their
      ability to produce embryos by SCNT were evaluated by testing the effects of
      tissue sample collection (DART biopsy, PUNCH biopsy, post-mortem EAR sample) and
      culture initiation (explant, collagenase digestion) techniques. RESULTS:
      Differences in initial sample size based on sample collection technique had an
      effect on the amount of time necessary for achieving primary confluence and the
      number of population doublings (PDL) produced. Thus, DART and PUNCH biopsies
      resulted in cultures with decreased lifespans (<30 PDL) accompanied by senescence
      like morphology and decreased normal chromosome content (<40% normal cells at 20
      PDL) compared to the long-lived (>50 PDL) and chromosomally stable (>70% normal
      cells at 20 PDL) cultures produced by post-mortem EAR samples. Chromosome
      stability was influenced by sample collection technique and was dependent upon
      the culture's initial telomere length and its rate of shortening over cell
      passages. Following SCNT, short-lived cultures resulted in significantly lower
      blastocyst development (< or = 0.9%) compared to highly proliferative cultures
      (11.8%). Chromosome stability and sample collection technique were significant
      factors in determining blastocyst development outcome. CONCLUSION: These data
      demonstrate the influence of culture establishment techniques on cell culture
      characteristics, including the viability, longevity and normality of cells. The
      identification of a quantifiable marker associated with SCNT embryo developmental
      potential, chromosome stability, provides a means by which cell culture
      conditions can be monitored and improved.

PMID- 16899120
TI  - Comparative evolutionary genomics of the HADH2 gene encoding Abeta-binding
      alcohol dehydrogenase/17beta-hydroxysteroid dehydrogenase type 10 (ABAD/HSD10).
AB  - BACKGROUND: The Abeta-binding alcohol dehydrogenase/17beta-hydroxysteroid
      dehydrogenase type 10 (ABAD/HSD10) is an enzyme involved in pivotal metabolic
      processes and in the mitochondrial dysfunction seen in the Alzheimer's disease.
      Here we use comparative genomic analyses to study the evolution of the HADH2 gene
      encoding ABAD/HSD10 across several eukaryotic species. RESULTS: Both vertebrate
      and nematode HADH2 genes showed a six-exon/five-intron organization while those
      of the insects had a reduced and varied number of exons (two to three). Eutherian
      mammal HADH2 genes revealed some highly conserved noncoding regions, which may
      indicate the presence of functional elements, namely in the upstream region about
      1 kb of the transcription start site and in the first part of intron 1. These
      regions were also conserved between Tetraodon and Fugu fishes. We identified a
      conserved alternative splicing event between human and dog, which have a nine
      amino acid deletion, causing the removal of the strand betaF. This strand is one
      of the seven strands that compose the core beta-sheet of the Rossman fold
      dinucleotide-binding motif characteristic of the short chain
      dehydrogenase/reductase (SDR) family members. However, the fact that the
      substrate binding cleft residues are retained and the existence of a shared
      variant between human and dog suggest that it might be functional. Molecular
      adaptation analyses across eutherian mammal orthologues revealed the existence of
      sites under positive selection, some of which being localized in the substrate
      binding cleft and in the insertion 1 region on loop D (an important region for
      the Abeta-binding to the enzyme). Interestingly, a higher than expected number of
      nonsynonymous substitutions were observed between human/chimpanzee and orangutan,
      with six out of the seven amino acid replacements being under molecular
      adaptation (including three in loop D and one in the substrate binding loop).
      CONCLUSION: Our study revealed that HADH2 genes maintained a reasonable conserved
      organization across a large evolutionary distance. The conserved noncoding
      regions identified among mammals and between pufferfishes, the evidence of an
      alternative splicing variant conserved between human and dog, and the detection
      of positive selection across eutherian mammals, may be of importance for further
      research on ABAD/HSD10 function and its implication in the Alzheimer's disease.

PMID- 16899121
TI  - Genomic structure and expression of uncoupling protein 2 genes in rainbow trout
      (Oncorhynchus mykiss).
AB  - BACKGROUND: Uncoupling protein 2 (UCP2) belongs to the superfamily of
      mitochondrial anion carriers that dissociate the respiratory chain from ATP
      synthesis. It has been determined that UCP2 plays a role in several physiological
      processes such as energy expenditure, body weight control and fatty acid
      metabolism in several vertebrate species. We report the first characterization of
      UCP2s in rainbow trout (Oncorhynchus mykiss). RESULTS: Two UCP2 genes were
      identified in the rainbow trout genome, UCP2A and UCP2B. These genes are 93%
      similar in their predicted amino acid sequences and display the same genomic
      structure as other vertebrates (8 exons and 7 introns) spanning 4.2 kb and 3.2
      kb, respectively. UCP2A and UCP2B were widely expressed in all tissues of the
      study with a predominant level in macrophage-rich tissues and reproductive
      organs. In fry muscle we observed an increase in UCP2B expression in response to
      fasting and a decrease after refeeding in agreement with previous studies in
      human, mouse, rat, and marsupials. The converse expression pattern was observed
      for UCP2A mRNA which decreased during fasting, suggesting different metabolic
      roles for UCP2A and UCP2B in rainbow trout muscle. Phylogenetic analysis
      including other genes from the UCP core family located rainbow trout UCP2A and
      UCP2B with their orthologs and suggested an early divergence of vertebrate UCPs
      from a common ancestor gene. CONCLUSION: We characterized two UCP2 genes in
      rainbow trout with similar genomic structures, amino acid sequences and
      distribution profiles. These genes appeared to be differentially regulated in
      response to fasting and refeeding in fry muscle. The genomic organization and
      phylogeny analysis support the hypothesis of a common ancestry between the
      vertebrate UCPs.

PMID- 16899122
TI  - HLA-DR expression on monocytes and systemic inflammation in patients with
      ruptured abdominal aortic aneurysms.
AB  - INTRODUCTION: Mortality from ruptured abdominal aortic aneurysms (RAAA) remains
      high. Severe systemic inflammation, leading to multi-organ failure, often occurs
      in these patients. In this study we describe the level of HLA-DR expression in a
      consecutive group of patients following surgery for RAAA and compare results
      between survivors and non-survivors. A similar comparison is made for IL-6, IL-10
      levels and SOFA-scores. METHODS: This is a prospective observational study.
      Patients with RAAA were prospectively analyzed. Blood samples were collected on
      day 1, 3, 5, 7, 10 and 14. The fraction of CD-14 positive monocytes expressing
      HLA-DR was measured by flow-cytometry. Interleukin-6 and interleukin-10 levels
      were measured by ELISA. RESULTS: Thirty patients with a median age of 70 years
      were included. There were 27 (90%) men. Six patients died from multiple organ
      failure, all other patients survived. The Sequential Organ Failure Assessment
      (SOFA) scores were significantly higher in non-survivors on day 1 through 14. HLA
      DR expression on monocytes was significantly lower on day 3, 5, 7, 10 and 14 in
      non-survivors. Interleukin-6 and IL-10 levels were significantly higher in non
      survivors on day 1 and day 1 and 3 respectively. CONCLUSIONS: HLA-DR expression
      on monocytes was decreased, especially in non-survivors. All patients with RAAA
      displayed a severe inflammatory and anti-inflammatory response with an increased
      production of IL-6 and IL-10. Poor outcome is associated with high levels of IL-6
      and IL-10 and a high SOFA score in the first three days after surgery, while low
      levels of HLA-DR expression are observed from day three after RAAA repair.

PMID- 16899123
TI  - Protocol for north of England and Scotland study of tonsillectomy and adeno
      tonsillectomy in children (NESSTAC). A pragmatic randomised controlled trial
      comparing surgical intervention with conventional medical treatment in children
      with recurrent sore throats.
AB  - BACKGROUND: Uncertainties surrounding the effectiveness and cost-effectiveness of
      childhood tonsillectomy for recurrent sore throat led the NHS Health Technology
      Assessment Programme to commission this research to evaluate the effectiveness
      and cost-effectiveness of tonsillectomy and adeno-tonsillectomy in comparison
      with standard non-surgical management in children aged under 16 with recurrent
      throat infections. The aim is to evaluate if tonsillectomy and adeno
      tonsillectomy reduces the number of episodes of sore throats among children to a
      clinically significant extent. METHODS/DESIGN: A simple prospective pragmatic
      randomised controlled trial with economic analysis and prospective cohort study
      of non-trial participants comparing surgical intervention with conventional
      medical treatment. The treatment arm will receive tonsillectomy and adeno
      tonsillectomy while in the control arm non-surgical conventional medical
      treatment only will be used. The primary outcome measure will be reported number
      of episodes of sore throat over two years with secondary outcomes measures of
      reported number of episodes of sore throat, otitis media and upper respiratory
      tract infection which invoke a GP consultation; reported number of symptom-free
      days; reported severity of sore throats and surgical and anaesthetic morbidity.
      The study will take place in five hospitals in the UK. The trial population will
      be 406 children aged 4-15 on their last birthday with recurrent sore throat
      referred by primary care to the 5 otolaryngology departments. The duration of the
      study is seven years (July 2001-July 2008). DISCUSSION: As with all pragmatic
      randomised controlled trials it is impossible to control the external environment
      in which the research is taking place. Since this trial began a number of factors
      have arisen which could affect the outcome including; a reduction in the
      incidence of respiratory tract infections, marked socio-economic differences in
      consultation rates, the results from the National Prospective Tonsillectomy Audit
      and the Government's waiting list initiatives.

PMID- 16899124
TI  - Barriers and facilitators to implementing shared decision-making in clinical
      practice: a systematic review of health professionals' perceptions.
AB  - BACKGROUND: Shared decision-making is advocated because of its potential to
      improve the quality of the decision-making process for patients and ultimately,
      patient outcomes. However, current evidence suggests that shared decision-making
      has not yet been widely adopted by health professionals. Therefore, a systematic
      review was performed on the barriers and facilitators to implementing shared
      decision-making in clinical practice as perceived by health professionals.
      METHODS: Covering the period from 1990 to March 2006, PubMed, Embase, CINHAL,
      PsycINFO, and Dissertation Abstracts were searched for studies in English or
      French. The references from included studies also were consulted. Studies were
      included if they reported on health professionals' perceived barriers and
      facilitators to implementing shared decision-making in their practices. Shared
      decision-making was defined as a joint process of decision making between health
      professionals and patients, or as decision support interventions including
      decision aids, or as the active participation of patients in decision making. No
      study design was excluded. Quality of the studies included was assessed
      independently by two of the authors. Using a pre-established taxonomy of barriers
      and facilitators to implementing clinical practice guidelines in practice,
      content analysis was performed. RESULTS: Thirty-one publications covering 28
      unique studies were included. Eleven studies were from the UK, eight from the
      USA, four from Canada, two from The Netherlands, and one from each of the
      following countries: France, Mexico, and Australia. Most of the studies used
      qualitative methods exclusively (18/28). Overall, the vast majority of
      participants (n = 2784) were physicians (89%). The three most often reported
      barriers were: time constraints (18/28), lack of applicability due to patient
      characteristics (12/28), and lack of applicability due to the clinical situation
      (12/28). The three most often reported facilitators were: provider motivation
      (15/28), positive impact on the clinical process (11/28), and positive impact on
      patient outcomes (10/28). CONCLUSION: This systematic review reveals that
      interventions to foster implementation of shared decision-making in clinical
      practice will need to address a broad range of factors. It also reveals that on
      this subject there is very little known about any health professionals others
      than physicians. Future studies about implementation of shared decision-making
      should target a more diverse group of health professionals.

PMID- 16899125
TI  - Intra-arterial adenoviral mediated tumor transfection in a novel model of cancer
      gene therapy.
AB  - BACKGROUND: The aim of the present study was to develop and characterize a novel
      in vivo cancer gene therapy model in which intra-arterial adenoviral gene
      delivery can be characterized. In this model, the rat cremaster muscle serves as
      the site for tumor growth and provides convenient and isolated access to the
      tumor parenchyma with discrete control of arterial and venous access for delivery
      of agents. RESULTS: Utilizing adenovirus encoding the green fluorescent protein
      we demonstrated broad tumor transfection. We also observed a dose dependent
      increment in luciferase activity at the tumor site using an adenovirus encoding
      the luciferase reporter gene. Finally, we tested the intra-arterial adenovirus
      dwelling time required to achieve optimal tumor transfection and observed a
      minimum time of 30 minutes. CONCLUSION: We conclude that adenovirus mediated
      tumor transfection grown in the cremaster muscle of athymic nude rats via an
      intra-arterial route could be achieved. This model allows definition of the
      variables that affect intra-arterial tumor transfection. This particular study
      suggests that allowing a defined intra-tumor dwelling time by controlling the
      blood flow of the affected organ during vector infusion can optimize intra
      arterial adenoviral delivery.

PMID- 16899126
TI  - Comparison of different methods in analyzing short-term air pollution effects in
      a cohort study of susceptible individuals.
AB  - BACKGROUND: Short-term fluctuations of ambient air pollution have been associated
      with exacerbation of cardiovascular disease. A multi-city study was designed to
      assess the probability of recurrent hospitalization in a cohort of incident
      myocardial infarction survivors in five European cities. The objective of this
      paper is to discuss the methods for analyzing short-term health effects in a
      cohort study based on a case-series. METHODS: Three methods were considered for
      the analyses of the cohort data: Poisson regression approach, case-crossover
      analyses and extended Cox regression analyses. The major challenge of these
      analyses is to appropriately consider changes within the cohort over time due to
      changes in the underlying risk following a myocardial infarction, slow time
      trends in risk factors within the population, dynamic cohort size and seasonal
      variation. RESULTS: Poisson regression analyses, case-crossover analyses and
      Extended Cox regression analyses gave similar results. Application of smoothing
      methods showed the capability to adequately model the complex time trends.
      CONCLUSION: From a practical point of view, Poisson regression analyses are less
      time-consuming, and therefore might be used for confounder selection and most of
      the analyses. However, replication of the results with Cox models is desirable to
      assure that the results are independent of the analytical approach used. In
      addition, extended Cox regression analyses would allow a joint estimation of long
      term and short-term health effects of time-varying exposures.

PMID- 16899127
TI  - Correction: a murine model of ulcerative colitis: induced with sinusitis-derived
      superantigen and food allergen. BMC Gastroenterol. 2005, 5:6.

PMID- 16899128
TI  - HTLV-1 Tax: centrosome amplification and cancer.
AB  - During interphase, each cell contains a single centrosome that acts as a
      microtubule organizing center for cellular functions in interphase and in
      mitosis. Centrosome amplification during the S phase of the cell cycle is a
      tightly regulated process to ensure that each daughter cell receives the proper
      complement of the genome. The controls that ensure that centrosomes are
      duplicated exactly once in the cell cycle are not well understood. In solid
      tumors and hematological malignancies, centrosome abnormalities resulting in
      aneuploidy is observed in the majority of cancers. These phenotypes are also
      observed in cancers induced by viruses, including adult T cell lymphoma which is
      caused by the human T cell lymphotrophic virus Type 1 (HTLV-1). Several reports
      have indicated that the HTLV-1 transactivator, Tax, is directly responsible for
      the centrosomal abnormalities observed in ATL cells. A recent paper in Nature
      Cell Biology by Ching et al. has shed some new light into how Tax may be inducing
      centrosome abnormalities. The authors demonstrated that 30% of ATL cells
      contained more than two centrosomes and expression of Tax alone induced
      supernumerary centrosomes. A cellular coiled-coil protein, Tax1BP2, was shown to
      interact with Tax and disruption of this interaction led to failure of Tax to
      induce centrosome amplification. Additionally, down-regulation of Tax1BP2 led to
      centrosome amplification. These results suggest that Tax1BP2 may be an important
      block to centrosome re-duplication that is observed in normal cells. Presently, a
      specific cellular protein that prevents centrosome re-duplication has not been
      identified. This paper has provided further insight into how Tax induces
      centrosome abnormalities that lead to ATL. Lastly, additional work on Tax1BP2
      will also provide insight into how the cell suppresses centrosome re-duplication
      during the cell cycle and the role that Tax1BP2 plays in this important cellular
      pathway.

PMID- 16899129
TI  - A case report of a new pulmonary embolism occurring in a patient receiving
      continuous infusion of recombinant activated protein C.
AB  - BACKGROUND: There are no guidelines governing the concomitant use of recombinant
      human activated protein C (rhAPC) and deep venous thrombosis/pulmonary embolism
      (DVT/PE) prophylaxis in critically ill patients. It is unknown if rhAPC provides
      any protection against DVT/PE in this population of patients. METHODS: Case
      report. RESULTS: This report describes the first case of a radiographically
      demonstrated pulmonary embolism occurring in a patient receiving continuous
      therapeutic infusion of rhAPC. CONCLUSION: The administration of rhAPC alone may
      not be sufficient DVT/PE prophylaxis in high risk patients. The risks associated
      with concomitant anticoagulation and rhAPC therapy are unknown. Further research
      is necessary to determine the safest and most effective regimen for DVT/PE
      prophylaxis in patients receiving rhAPC.

PMID- 16899130
TI  - How are health professionals earning their living in Malawi?
AB  - BACKGROUND: The migration of health professionals from southern Africa to
      developed nations is negatively affecting the delivery of health care services in
      the source countries. Oftentimes however, it is the reasons for the out-migration
      that have been described in the literature. The work and domestic situations of
      those health professionals continuing to serve in their posts have not been
      adequately studied. METHODS: The present study utilized a qualitative data
      collection and analysis method. This was achieved through focus group discussions
      and in-depth interviews with health professionals and administrators to determine
      the challenges they face and the coping systems they resort to and the
      perceptions towards those coping methods. RESULTS: Health professionals
      identified the following as some of the challenges there faced: inequitable and
      poor remuneration, overwhelming responsibilities with limited resources, lack of
      a stimulating work environment, inadequate supervision, poor access to continued
      professionals training, limited career progression, lack of transparent
      recruitment and discriminatory remuneration. When asked what kept them still
      working in Malawi when the pressures to emigrate were there, the following were
      some of the ways the health professionals mentioned as useful for earning extra
      income to support their families: working in rural areas where life was perceived
      to be cheaper, working closer to home village so as to run farms, stealing drugs
      from health facilities, having more than one job, running small to medium scale
      businesses. Health professionals would also minimize expenditure by missing meals
      and walking to work. CONCLUSION: Many health professionals in Malawi experience
      overly challenging environments. In order to survive some are involved in
      ethically and legally questionable activities such as receiving "gifts" from
      patients and pilfering drugs. The efforts by the Malawi government and the
      international community to retain health workers in Malawi are recognized. There
      is however need to evaluate of these human resources-retaining measures are
      having the desired effects.

PMID- 16899132
TI  - Insite: Canada's landmark safe injecting program at risk.
AB  - InSite is North Americas first supervised injection site and a landmark public
      heath initiative operating in Vancouver since 2003. The program is a vital
      component of that cities internationally recognized harm reduction approach to
      its serious problems with drugs, crime, homelessness and AIDS. InSite currently
      operates under a waiver of Federal rules that allow it to provide services as a
      research project. An extensive evaluation has produced very positive results for
      thousands of users. Normally such strong evidence documenting the successes of
      such a program, and the medical and public health significance of these positive
      outcomes, would be the basis for celebration and moves to expand the model and
      provide similar services elsewhere in Canada. Instead, there is a distinct
      possibility that InSite will be closed by the newly elected Canadian Prime
      Minister Paul Harper--a conservative who has traveled to the US to visit George
      WQ Bush and come back antagonistic to harm reduction in all its forms. Because
      InSites federal waiver is expiring and up for renewal in September, the fear is
      that Mr. Harpers will not renew the approval and that the program will be forced
      to close down. The risks associated with the potential closure of InSite need to
      be fully understood. This editorial lays out these public health risks and the
      associated economic impact if InSite were to be closed. In addition to
      preventable deaths and disease, InSites closure will cost Vancouver and British
      Columbia between $3.8 and $8.8 million in preventable health care expenses over
      the next two years.

PMID- 16899131
TI  - Analyses of variant human papillomavirus type-16 E5 proteins for their ability to
      induce mitogenesis of murine fibroblasts.
AB  - BACKGROUND: Human papillomavirus type 16 (HPV-16) E5 protein co-operates with
      epidermal growth factor to stimulate mitogenesis of murine fibroblasts.
      Currently, little is known about which viral amino acids are involved in this
      process. Using sequence variants of HPV-16 E5 we have investigated their effects
      upon E5 transcription, cell-cycling and cell-growth of murine fibroblasts.
      RESULTS: We demonstrate that: (i) introduction of Thr64 into the reference E5
      sequence of HPV-16 abrogates mitogenic activity: both were poorly transcribed in
      NIH-3T3 cells; (ii) substitution of Leu44Val65 or, Thr37Leu44Val65 into the HPV
      16 E5 reference backbone resulted in high transcription in NIH-3T3 cells,
      enhanced cell-cycle progression and high cell-growth; and, (iii) inclusion of
      Tyr8 into the Leu44Val65 backbone inhibited E5 induced cell-growth and repression
      of p21 expression, despite high transcription levels. CONCLUSION: The effects of
      HPV-16 E5 variants upon mitosis help to explain why Leu44Val65 HPV-16 E5 variants
      are most prevalent in 'wild' pathogenic viral populations in the UK.

PMID- 16899133
TI  - "Nutritional and chemopreventive anti-cancer agents up-regulate expression of
      p27Kip1, a cyclin-dependent kinase inhibitor, in mouse JB6 epidermal and human
      MCF7, MDA-MB-321 and AU565 breast cancer cells".
AB  - BACKGROUND: p27(Kip1) is a cyclin-dependent kinase inhibitor. When up-regulated,
      p27 inhibits G1-to-S phase transition of the cell cycle. This report addresses
      the question of whether various nutritional and chemopreventive anti-cancer
      agents up-regulate the expression of p27 in preneoplastic and neoplastic cells.
      RESULTS: Experimental evidence presented in the first half of this report shows
      that these agents fairly faithfully up-regulate expression of p27 in mouse
      epidermal (JB6) and human breast cancer (MCF7, MDA-MB-321, and AU565) cells. Up
      regulation appears to be specific to p27 because expression of cyclin D1, E, and
      A, and p21Cip1/Waf1 was not modulated by these agents. Up-regulation of the
      expression of p27 is likely due to the activation of translation rather than
      transcription of p27 because (a) up-regulation is mediated by the 5'-untranslated
      region (-575) of the p27 gene and (b) the antibiotic actinomycin D, an inhibitor
      of transcription, did not attenuate the up-regulation of p27. This latter finding
      is likely to preclude the existence of cryptic transcription factor binding
      site(s) in the 5'-untranslated region of p27 gene. The experimental evidence,
      presented in the second half of this report, was obtained using the 5'
      untranslated region (-575) of p27 gene. The evidence suggests that cancer
      preventive agents up-regulate expression of p27 by at least four different
      molecular signaling pathways: (a) Caloric restriction is likely to up-regulate
      p27 expression via 5'-AMP-activated protein kinase (AMPK; a metabolic energy
      sensor or cellular fuel gauge), tuberous sclerosis complex (TSC), and mammalian
      target of rapamycin (mTOR). Amino acid deficiencies also up-regulate the
      expression of p27 using some components of this pathway. (b) 4-Hydroxytamoxifen
      (but not tamoxifen), genistein (but not genistin), daidzein, and probably other
      nutritional and chemopreventive anti-cancer agents could up-regulate expression
      of p27 via receptor protein tyrosine kinases (RPTKs), phosphoinositide 3-kinase
      (PI3K), phosphoinosite-dependent kinase (PDK), Akt/PKB and mTOR. (c) Expression
      of p27 could also be up-regulated via RPTKs followed by MAPKs--MEK, ERK and
      p38MAPK--and probably MNK. Finally, (d) global hypomethylation of 5'-m7G cap of
      mRNAs could also up-regulate expression of p27. CONCLUSION: Based on these
      findings, we conclude that various nutritional and chemopreventive anti-cancer
      agents up-regulate expression of p27 in (pre)neoplastic cells.

PMID- 16899134
TI  - Gene and protein nomenclature in public databases.
AB  - BACKGROUND: Frequently, several alternative names are in use for biological
      objects such as genes and proteins. Applications like manual literature search,
      automated text-mining, named entity identification, gene/protein annotation, and
      linking of knowledge from different information sources require the knowledge of
      all used names referring to a given gene or protein. Various organism-specific or
      general public databases aim at organizing knowledge about genes and proteins.
      These databases can be used for deriving gene and protein name dictionaries. So
      far, little is known about the differences between databases in terms of size,
      ambiguities and overlap. RESULTS: We compiled five gene and protein name
      dictionaries for each of the five model organisms (yeast, fly, mouse, rat, and
      human) from different organism-specific and general public databases. We analyzed
      the degree of ambiguity of gene and protein names within and between
      dictionaries, to a lexicon of common English words and domain-related non-gene
      terms, and we compared different data sources in terms of size of extracted
      dictionaries and overlap of synonyms between those. The study shows that the
      number of genes/proteins and synonyms covered in individual databases varies
      significantly for a given organism, and that the degree of ambiguity of synonyms
      varies significantly between different organisms. Furthermore, it shows that,
      despite considerable efforts of co-curation, the overlap of synonyms in different
      data sources is rather moderate and that the degree of ambiguity of gene names
      with common English words and domain-related non-gene terms varies depending on
      the considered organism. CONCLUSION: In conclusion, these results indicate that
      the combination of data contained in different databases allows the generation of
      gene and protein name dictionaries that contain significantly more used names
      than dictionaries obtained from individual data sources. Furthermore, curation of
      combined dictionaries considerably increases size and decreases ambiguity. The
      entries of the curated synonym dictionary are available for manual querying,
      editing, and PubMed- or Google-search via the ProThesaurus-wiki. For automated
      querying via custom software, we offer a web service and an exemplary client
      application.

PMID- 16899135
TI  - Identification and analysis of gene families from the duplicated genome of
      soybean using EST sequences.
AB  - BACKGROUND: Large scale gene analysis of most organisms is hampered by incomplete
      genomic sequences. In many organisms, such as soybean, the best source of
      sequence information is the existence of expressed sequence tag (EST) libraries.
      Soybean has a large (1115 Mbp) genome that has yet to be fully sequenced. However
      it does have the 6th largest EST collection comprised of ESTs from a variety of
      soybean genotypes. Many EST libraries were constructed from RNA extracted from
      various genetic backgrounds, thus gene identification from these sources is
      complicated by the existence of both gene and allele sequence differences. We
      used the ESTminer suite of programs to identify potential soybean gene
      transcripts from a single genetic background allowing us to observe functional
      classifications between gene families as well as structural differences between
      genes and gene paralogs within families. The identification of potential gene
      sequences (pHaps) from soybean allows us to begin to get a picture of the genomic
      history of the organism as well as begin to observe the evolutionary fates of
      gene copies in this highly duplicated genome. RESULTS: We identified
      approximately 45,000 potential gene sequences (pHaps) from EST sequences of
      Williams/Williams82, an inbred genotype of soybean (Glycine max L. Merr.) using a
      redundancy criterion to identify reproducible sequence differences between
      related genes within gene families. Analysis of these sequences revealed single
      base substitutions and single base indels are the most frequently observed form
      of sequence variation between genes within families in the dataset. Genomic
      sequencing of selected loci indicate that intron-like intervening sequences are
      numerous and are approximately 220 bp in length. Functional annotation of gene
      sequences indicate functional classifications are not randomly distributed among
      gene families containing few or many genes. CONCLUSION: The predominance of
      single nucleotide insertion/deletions and substitution events between genes
      within families (individual genes and gene paralogs) is consistent with a model
      of gene amplification followed by single base random mutational events expected
      under the classical model of duplicated gene evolution. Molecular functions of
      small and large gene families appear to be non-randomly distributed possibly
      indicating a difference in retention of duplicates or local expansion.

PMID- 16899136
TI  - Ectopic thyroid in an adrenal mass: a case report.
AB  - BACKGROUND: It is difficult to explain ectopic thyroid beneath the diaphragm
      because during the development the thyroid descends from the tongue to the
      anterior of the trachea. A few cases of ectopic lesions have been reported in the
      literature for abdominal organs including the adrenal glands, but the mechanism
      by which the thyroid components migrate into the abdomen has been poorly
      understood. CASE PRESENTATION: A 54-year-old woman was diagnosed as having an
      adrenal mass. Laparoscopic adrenalectomy was carried out. Microscopically, the
      mass was composed of normal adrenal and ectopic thyroid tissues. CONCLUSION: We
      herein describe the fourth case reported of ectopic thyroid in the adrenal gland.

PMID- 16899137
TI  - Epidemiological tracing of Salmonella enterica serotype Abortusovis from Spanish
      ovine flocks by PFGE fingerprinting.
AB  - Salmonella enterica serotype Abortusovis, an ovine host-specific serotype, rare
      in most countries, is responsible for epidemic abortion episodes in Spain. With
      the aim of surveillance and detection of the spread of specific clones, 55
      Abortusovis isolates collected during 1996-2001 from flocks in 11 provinces, were
      studied using XbaI-PFGE. Despite the fact that the strains were geographically
      and spatially related, PFGE demonstrated an epidemiologically acceptable
      discriminating power, identifying 20 clones (similarity, 52-96%). Clones Sabv6,
      1, 5 were disseminated in seven, five and two areas respectively, while another
      17 clones appeared in single places. Clones from nearby geographic regions showed
      a high relatedness (one band of difference in the PFGE profile) Sabv1-2-3, Sabv5
      6, Sabv7-8, and Sabv13-14, suggesting a common ancestor. Co-isolation in the same
      flock (Sabv5-6, Sabv1-3, Sabv1-6) was detected. PFGE surveillance detected the
      predominance and widespread distribution of clone Sabv6 in 21 out of the 55
      Abortusovis serotype episodes studied in Spain.

PMID- 16899138
TI  - Molecular characterization of the Cryptosporidium cervine genotype.
AB  - In this study, the 27 kDa immunodominant antigen (CP23), 70 kDa heat shock
      protein (HSP70), actin and beta-tubulin genes were amplified and sequenced for
      the first time from human isolates of Cryptosporidium cervine genotype. New
      primers were designed from reported sequences of other Cryptosporidium species
      and genotypes as well as the whole genome sequences of C. parvum and C. hominis,
      which enabled novel gene sequences and regions extending beyond those deposited
      in GenBank to be determined. In comparison with other species in the
      Cryptosporidium genus, multiple sequence alignment and phylogenetic analysis
      revealed that the Cryptosporidium cervine genotype isolates from humans clustered
      most closely with Cryptosporidium deer mouse genotype and C. suis (n. sp.
      formerly pig genotype I). The complete coding sequence of CP23 was determined to
      reveal low (72.4% and 68.0-69.8% respectively) identity to C. parvum and C.
      hominis sequences and the presence of a unique multiple proline-alanine-proline
      valine (PAPV) repeat region.

PMID- 16899139
TI  - The life-cycle of Philornis downsi (Diptera: Muscidae) parasitizing Darwin's
      finches and its impacts on nestling survival.
AB  - The fly, Philornis downsi Dodge & Aitken, was first collected in 1964 on the
      Galapagos Islands and is now widespread across the archipelago. Virtually nothing
      is known about the behaviour and ecology of the fly as well as for the genus in
      general. Here, we describe all larval instars for the first time, and discuss
      infection intensity and impacts of parasitism on nestling survival of Darwin's
      finches. Adult P. downsi are non-parasitic free-living flies, whereas the larvae
      are obligate blood-feeding parasites on nestling birds. The larvae show a marked
      shift in their host site specificity--a novel finding for the genus Philornis:
      the first and early second larval instars live as agents of myiasis in finch
      nostrils and other tissues, while the older second and third instar larvae reside
      in the nest material and feed externally on the blood of nestlings, leading to
      blood losses in nestlings of 18-55%. Pupation occurs in the bottom layer of the
      nest. The combined effects of tissue damage by the endoparasitic instar larvae
      and anaemia by nest-dwelling haematophagous instar larvae account for the high
      nestling mortality (76%) due to Philornis parasitism. This represents the highest
      mortality by Philornis reported in the literature and emphasizes the extremely
      serious threat this parasite poses for the endemic passerine fauna of the
      Galapagos Islands.

PMID- 16899140
TI  - Characterization of D-glucose transport in Trypanosoma rangeli.
AB  - Like in other trypanosomatids D-glucose is a crucial source of energy to
      Trypanosoma rangeli, a non-pathogenic parasite that in Central and South America
      infects triatomine vectors and different mammalian species, including humans. In
      several trypanosome species, D-glucose transporters were already described and
      cloned. In this study, we characterized the D-glucose transport activity present
      in 2 life-stage forms of T. rangeli (epimastigotes and trypomastigotes) using D
      [U-14C]glucose as substrate. Our results indicate that T. rangeli transports D
      glucose with high affinity in both epimastigote (Km 30 microM) and
      trypomastigotes (Km 80 microM) life-forms. Both transport activities were
      inhibited by Cytochalasin B and Phloretin, indicating that probably D-glucose
      uptake in T. rangeli is mediated by facilitated diffusion of the sugar.
      Significant differences were observed between epimastigotes and trypomastigotes
      in relation to their affinity for D-glucose analogues, and the predicted amino
      acid sequence of a putative D-glucose transporter from T. rangeli (TrHT1) showed
      a larger identity with the T. cruzi D-glucose transporter encoded by the TcrHT1
      gene than with other transporters already characterized in trypanosomatids.

PMID- 16899141
TI  - Molecular cloning and characterization of an Rcd1-like protein in excretory
      secretory products of Trichinella pseudospiralis.
AB  - A cDNA library was constructed from muscle larvae of Trichinella pseudospiralis.
      A cDNA clone, designated as Tp8 contained a cDNA transcript of 1326 bp length
      with a single open reading frame, which encoded 303 amino acid residues (34,187
      Da, estimated molecular mass). The predicted amino acid sequence of the clone had
      an identity of approximately 60% to the Rcd1 (Required cell differentiation 1) 
      like proteins among a wide range of organisms. Real-time quantitative polymerase
      chain reaction results showed that the transcription level of Tp8 gene reached
      the highest value in adult worms, and that the transcription level in muscle
      larvae before stichosome formation was higher than in muscle larvae after
      stichosome formation. The recombinant Tp8 protein migrated at 37 kDa and reacted
      to antibody against T. pseudospiralis excretory-secretory (E-S) products and sera
      from mice infected with T. pseudospiralis. An antibody against the Tp8
      recombinant protein could stain proteins migrating at approximately 34 kDa (which
      is the expected size from the sequence) on Western blotting of E-S products from
      muscle larvae. An immunocytochemical study showed that the Tp8 protein was
      present within the stichocyte of muscle larvae and adults worms.

PMID- 16899143
TI  - Health, development and the Millennium Development Goals.
AB  - The Millennium Development Goals (MDG), which emerged from the United Nations
      Millennium Summit in 2000, are increasingly recognized as the over-arching
      development framework. As such, the MDG are increasingly guiding the policies of
      poor countries and aid agencies alike. This article reviews the challenges and
      opportunities for health presented by the MDG. The opportunities include that
      three of the eight MDG relate to health--a recognition that health is central to
      global agenda of reducing poverty, as well as an important measure of human well
      being in its own right. A related point is that the MDG help to focus attention
      on those health conditions that disproportionally affect the poor (communicable
      disease, child health and maternal health), which should, in turn, help to
      strengthen the equity focus of health policies in low-income countries. Further,
      because the MDG are concrete, it is possible to calculate the cost of achieving
      them, which in turn strengthens the long-standing calls for higher levels of aid
      for health. The challenges include that, while the MDG focus on specific diseases
      and conditions, they cannot be achieved without strengthening health systems.
      Similarly, progress towards the MDG will require health to be prioritized within
      overall development and economic policies. In practice, this means applying a
      health 'lens' to processes such as civil-service reform, decentralization and the
      drawing-up of frameworks of national expenditure. Finally, the MDG cannot be met
      with the resources available in low-income countries. While the MDG framework has
      created pressure for donors to commit to higher levels of aid, the challenge
      remains to turn these commitments into action. Data are presented to show that,
      at current rates of progress, the health-related MDG will not be achieved. This
      disappointing trend could be reversed, however, if the various challenges
      outlined are met.

PMID- 16899144
TI  - Breaking the poor health-poverty link in the 21st Century: do health systems help
      or hinder?
AB  - It is depressing but true that, at the beginning of the 21st Century, poverty and
      ill-health are still closely interrelated. This review traces the current
      pathways from poor health to poverty in low- and middle-income countries, first
      at the national level, then at the household level. Ill health can have a
      substantial impact on gross domestic product, holding countries back from
      economic development, the fruits of which could be used to improve population
      health. At the household level, people may be pushed into poverty as a result of
      paying for health care. Households are forced to pay for the direct and indirect
      costs of health care at precisely the time when their incomes may be lowered by
      ill health. For this reason, many forego care, or rely on self-care or informal
      care, which may hasten the decline in their health and reduce their productivity.
      Sick people face a double jeopardy: their ill-health puts them at greater risk of
      poverty, and their poverty is likely to damage their health still further. The
      review goes on to discuss the role of health systems in the generation of
      poverty, before concluding with pointers as to how health systems can become part
      of the solution, rather than part of the problem.

PMID- 16899145
TI  - Eradicating polio: today's challenges and tomorrow's legacy.
AB  - Since its launch in 1988, the Global Polio Eradication Initiative has grown into
      one of the largest international health efforts in history, operating in every
      country and area in the world. The burden of polio disease has been reduced by
      over 99%, and the number of countries with indigenous virus has fallen from more
      than 125 to just four. As importantly, a strong surveillance and laboratory
      infrastructure has been established for vaccine-preventable diseases (including
      measles, tetanus, yellow fever, rubella and Japanese encephalitis), and a massive
      investment has been made in the physical infrastructure and human resources
      needed to deliver routine immunizations and other health services in developing
      countries. Between 2000 and 2003, new challenges to polio eradication emerged,
      threatening the interruption of the transmission of wild poliovirus globally and
      the eventual elimination of any residual polio disease as the result of the
      continued use of oral polio vaccines. By the end of 2005, a range of solutions
      had been developed to address these late challenges, including two new monovalent
      oral polio vaccines, new and robust international standards for the response to
      polio outbreaks, and renewed political commitment across the countries that
      remain infected. As importantly, a comprehensive strategy had been established
      for managing the long-term risks of paralytic polio, centred, ironically, on the
      eventual elimination from routine immunizations of the vaccine that is still
      central to the success of the global eradication effort.

PMID- 16899146
TI  - Tuberculosis.
AB  - Tuberculosis (TB) is a disease of antiquity, caused by Mycobacterium
      tuberculosis, which principally affects the lungs. It is a major public-health
      problem, with around 9 million new cases and 2 million deaths estimated to occur
      each year. Patients with pulmonary TB whose sputum is smear-positive for M.
      tuberculosis form the main source of infection in communities. About 5%-10% of
      infected individuals are likely to develop symptomatic TB during their lives but
      the risk of developing the clinical manifestations of the disease is greatly
      increased by HIV co-infection. The strong association between HIV and TB in sub
      Saharan Africa is responsible for the massive increase in the incidence of TB
      observed in that region in the last 20 years. Diagnosis of TB in resource-poor
      countries is largely based on sputum-smear microscopy and chest radiography,
      although these methods lack sensitivity or specificity, especially when used on
      HIV-infected patients. Effective treatment has existed for 40 years but TB
      attributable mortality remains high among HIV-infected patients in Africa, who
      are also particularly likely to develop TB again after receiving drug treatment
      for the disease. In Eastern Europe it is drug resistance in the local M.
      tuberculosis that makes the treatment of TB relatively ineffective. The approach
      to TB control that is now internationally recommended is the DOTS ('directly
      observed treatment, short-course') strategy, which aims to prevent the
      transmission of M. tuberculosis, and the related illness and death, by using
      combinations of anti-TB drugs to treat patients with the active disease.
      Unfortunately, countries in sub-Saharan Africa are falling short of the World
      Health Organization's targets for case detection and treatment. This failure is,
      in turn, making the achievement of the Millennium Development Goals for TB--to
      ensure that the incidence of TB is falling by 2015 and to halve the prevalence of
      TB and the annual number of TB-attributable deaths between 1990 and 2015--less
      likely. To improve the performance and impact of TB-control programmes, in the
      face of HIV co-infection and other constraints on DOTS, the World Health
      Organization has launched the revised 'Stop TB Strategy'. The new strategy, to be
      implemented via the Global Plan to Stop TB (2006-2015), includes intensified TB
      case finding, treatment of latent TB infection with isoniazid, prevention of HIV
      infection, cotrimoxazole preventive therapy, and antiretroviral therapy.

PMID- 16899147
TI  - Human immunodeficiency virus (HIV) in developing countries.
AB  - The human immunodeficiency virus (HIV) is causing the most destructive epidemic
      of recent times, having been responsible for the deaths of more than 25 million
      people since it was first recognised in 1981. This global epidemic remains out of
      control, with reported figures for 2005 of 40 million people infected with HIV.
      During 2005 there were 4.9 million new infections, showing that transmission is
      not being prevented, and there were 3.1 million deaths from the acquired
      immunodeficiency syndrome (AIDS), reflecting the lack of a definitive cure and
      the limited access to suppressive antiretroviral treatment in the developing
      countries that are most severely affected. The current state of the epidemic and
      the response to date are here reviewed. Present and future opportunities for
      prevention, treatment and surveillance are discussed, with particular reference
      to progress towards an HIV vaccine, the expansion of the provision of highly
      active antiretroviral therapy, and the need to focus control programmes on HIV as
      an infectious disease, rather than as a development issue.

PMID- 16899148
TI  - Chronic non-communicable diseases.
AB  - Chronic non-communicable diseases (NCD) account for almost 60% of global
      mortality, and 80% of deaths from NCD occur in low- and middle-income countries.
      One quarter of these deaths--almost 9 million in 2005--are in men and women aged
      <60 years. Taken together, NCD represent globally the single largest cause of
      mortality in people of working age, and their incidences in younger adults are
      substantially higher in the poor countries of the world than in the rich. The
      major causes of NCD-attributable mortality are cardiovascular disease (30% of
      total global mortality), cancers (13%), chronic respiratory disease (7%) and
      diabetes (2%). These conditions share a small number of behavioural risk factors,
      which include a diet high in saturated fat and low in fresh fruit and vegetables,
      physical inactivity, tobacco smoking, and alcohol excess. In low- and middle
      income countries such risk factors tend to be concentrated in urban areas and
      their prevalences are increasing as a result of rapid urbanization and the
      increasing globalisation of the food, tobacco and alcohol industries. Because NCD
      have a major impact on men and women of working age and their elderly dependents,
      they result in lost income, lost opportunities for investment, and overall lower
      levels of economic development. Reductions in the incidences of many NCD and
      their complications are, however, already possible. Up to 80% of all cases of
      cardiovascular disease or type-2 diabetes and 40% of all cases of cancer, for
      example, are probably preventable based on current knowledge. In addition, highly
      cost-effective measures exist for the prevention of some of the complications of
      established cardiovascular disease and diabetes. Achieving these gains will
      require a broad range of integrated, population-based interventions as well as
      measures focused on the individuals at high risk. At present, the international
      assistance community provides scant resources for the control of NCD in poor
      countries, partly, at least, because NCD continue to be wrongly perceived as
      predominantly diseases of the better off. As urbanization continues apace and
      populations age, investment in the prevention and control of NCD in low-and
      middle-income countries can no longer be ignored.

PMID- 16899149
TI  - A century of smoke.
AB  - Tobacco kills 5 million people annually. By the mid 2020s, that figure will
      increase to about 10 million a year, with most of the deaths occurring in
      developing countries. This review explains how early technological and regulatory
      developments contributed to the epidemic, reveals the efforts of the tobacco
      industry to conceal its products' harmfulness, and stresses the role of the
      globalization of trade and marketing as a means of increasing consumption world
      wide. The results of tens of thousands of studies published globally over the
      past 50 years point to an association between smoking and lung cancer and other
      adverse health effects, and the non-smoker's rights movement has exposed the wide
      spread perils of 'secondhand' smoke. Yet, the tobacco industry continues its
      global expansion, and consumers in low- and middle-income countries are
      especially susceptible to its marketing tactics. This review ends by emphasising
      the need for a global public-health response, and identifies the Framework
      Convention on Tobacco Control as a significant effort. It stresses the need for
      accelerated action and innovative tobacco-control efforts, if the projected death
      toll is to be reduced in this century.

PMID- 16899150
TI  - Measuring the global burden of disease and epidemiological transitions: 2002
      2030.
AB  - Any planning process for health development ought to be based on a thorough
      understanding of the health needs of the population. This should be sufficiently
      comprehensive to include the causes of premature death and of disability, as well
      as the major risk factors that underlie disease and injury. To be truly useful to
      inform health-policy debates, such an assessment is needed across a large number
      of diseases, injuries and risk factors, in order to guide prioritization. The
      results of the original Global Burden of Disease Study and, particularly, those
      of its 2000-2002 update provide a conceptual and methodological framework to
      quantify and compare the health of populations using a summary measure of both
      mortality and disability: the disability-adjusted life-year (DALY). Globally, it
      appears that about 56 million deaths occur each year, 10.5 million (almost all in
      poor countries) in children. Of the child deaths, about one-fifth result from
      perinatal causes such as birth asphyxia and birth trauma, and only slightly less
      from lower respiratory infections. Annually, diarrhoeal diseases kill over 1.5
      million children, and malaria, measles and HIV/AIDS each claim between 500,000
      and 800,000 children. HIV/AIDS is the fourth leading cause of death world-wide
      (2.9 million deaths) and the leading cause in Africa. The top three causes of
      death globally are ischaemic heart disease (7.2 million deaths), stroke (5.5
      million) and lower respiratory diseases (3.9 million). Chronic obstructive lung
      diseases (COPD) cause almost as many deaths as HIV/AIDS (2.7 million). The
      leading causes of DALY, on the other hand, include causes that are common at
      young ages [perinatal conditions (7.1% of global DALY), lower respiratory
      infections (6.7%), and diarrhoeal diseases (4.7%)] as well as depression (4.1%).
      Ischaemic heart disease and stroke rank sixth and seventh, retrospectively, as
      causes of global disease burden, followed by road traffic accidents, malaria and
      tuberculosis. Projections to 2030 indicate that, although these major vascular
      diseases will remain leading causes of global disease burden, with HIV/AIDS the
      leading cause, diarrhoeal diseases and lower respiratory infections will be
      outranked by COPD, in part reflecting the projected increases in death and
      disability from tobacco use.

PMID- 16899151
TI  - Globalisation, complex humanitarian emergencies and health.
AB  - A new political economy of conflict has emerged in the aftermath of colonialism
      and the Cold War. Complex political emergencies have been simmering in the post
      colonial world for more than three decades. Intra-country armed conflict, often
      combined with natural disasters, at present contributes to the displacement of
      over 20 million people world-wide. The international community remains profoundly
      uncomfortable with the complex political emergencies of the new era, torn between
      the respect for national sovereignty upon which the international political
      system of the United Nations and other agencies is built, and the growth of
      concern with human rights and a burgeoning International Humanitarian Law.
      Globalisation may have brought many benefits to some but there are also many
      losers. The Word Bank and the International Monetary Fund imposed structural
      adjustment policies to ensure debt repayment and economic restructuring that have
      resulted in a net reduction in expenditure on health, education and development.
      A downward spiral has been created of debt, disease, malnutrition, missed
      education, economic entrapment, poverty, powerlessness, marginalization,
      migration and instability. Africa's complex political emergencies are
      particularly virulent and tenacious. Three examples that are among the most
      serious humanitarian emergencies to have faced the world in recent times--those
      in Angola, the Democratic Republic of Congo and Sudan--are reviewed here in
      detail. The political evolution of these emergencies and their impact on the
      health of the affected populations are also explored.

PMID- 16899152
TI  - Urbanization and tropical health--then and now.
AB  - Since the launch of the Annals of Tropical Medicine and Parasitology 100 years
      ago, the percentage of the world's population living in urban settings has more
      than tripled and is now approaching 50%. Urbanization will continue at a high
      pace, particularly in the less developed regions of Africa and Asia. The profound
      demographic, ecological and socio-economic transformations that accompany the
      process of urbanization have important impacts on health and well-being. In
      industrialized countries, urbanization led to the so-called 'epidemiological
      transition', from acute infectious and deficiency diseases to chronic non
      communicable diseases, many decades ago. In the developing world, surprisingly
      little research has been carried out on the health-related aspects of
      urbanization. In a temporal analysis of publications in the Annals of Tropical
      Medicine and Parasitology, for example, in which the first volume in every decade
      from 1907 was examined, only 16 (2.6%) of the 604 articles investigated focused
      on epidemiological and/or public-health issues in urban tropical settings. This
      review begins with the question 'what is urban?' and then provides a summary of
      the trends seen in urbanization, and its impacts on human health, over the past
      century, on both a global and regional scale. For the main tropical diseases,
      estimates of the at-risk populations and the numbers of cases are updated and
      then split into urban and non-urban categories. The inhabitants of urban slums
      are particularly vulnerable to many of these diseases and require special
      attention if internationally-set targets for development are to be met.
      Heterogeneity, a major feature of urban settings in the tropics that complicates
      all efforts at health improvement, is demonstrated in an exploration of a densely
      populated municipality of a large West African town. Urban planners, public
      health experts and other relevant stakeholders clearly need to make much more
      progress in alleviating poverty and enhancing the health and well-being of urban
      residents, in an equity-effective and sustainable manner.

PMID- 16899153
TI  - Climate change and health: global to local influences on disease risk.
AB  - The World Health Organization has concluded that the climatic changes that have
      occurred since the mid 1970s could already be causing annually over 150,000
      deaths and five million disability-adjusted life-years (DALY), mainly in
      developing countries. The less developed countries are, ironically, those least
      responsible for causing global warming. Many health outcomes and diseases are
      sensitive to climate, including: heat-related mortality or morbidity; air
      pollution-related illnesses; infectious diseases, particularly those transmitted,
      indirectly, via water or by insect or rodent vectors; and refugee health issues
      linked to forced population migration. Yet, changing landscapes can significantly
      affect local weather more acutely than long-term climate change. Land-cover
      change can influence micro-climatic conditions, including temperature, evapo
      transpiration and surface run-off, that are key determinants in the emergence of
      many infectious diseases. To improve risk assessment and risk management of these
      synergistic processes (climate and land-use change), more collaborative efforts
      in research, training and policy-decision support, across the fields of health,
      environment, sociology and economics, are required.

PMID- 16899154
TI  - Multivariate genetic analysis of sex limitation and G x E interaction.
AB  - Sex-limited expression of genetic or environmental factors occurs in two basic
      forms. First, the effects of a factor may be larger on one sex than on another,
      which is known as scalar sex limitation. Second, some factors may have an effect
      on one sex but not on the other, which is called nonscalar sex limitation. In the
      classical twin study, scalar sex-limited effects cause same-sex male and same-sex
      female twin correlations to differ. Nonscalar sex-limited effects would cause the
      correlations between opposite-sex pairs of relatives to be lower than would be
      expected from the correlations between relatives of the same sex. One approach to
      modeling such effects is to allow the genetic correlation between opposite-sex
      dizygotic twins to be less than one-half; another is to allow the common
      environment correlation for opposite-sex pairs to be less than unity. Extension
      of this approach to the multivariate case is not straightforward. Direct
      extension of the Cholesky decomposition such that each Cholesky factor is allowed
      to correlate less than one-half in opposite-sex pairs yields a model where the
      order of the variables can change the goodness-of-fit of the model. It is shown
      that similar problems exist with a variety of multivariate and longitudinal
      models, and in a variety of models of genotype x environment interaction. Several
      solutions to these problems are described.

PMID- 16899155
TI  - A note on the asymptotic distribution of likelihood ratio tests to test variance
      components.
AB  - When using maximum likelihood methods to estimate genetic and environmental
      components of (co)variance, it is common to test hypotheses using likelihood
      ratio tests, since such tests have desirable asymptotic properties. In
      particular, the standard likelihood ratio test statistic is assumed
      asymptotically to follow a chi2 distribution with degrees of freedom equal to the
      number of parameters tested. Using the relationship between least squares and
      maximum likelihood estimators for balanced designs, it is shown why the
      asymptotic distribution of the likelihood ratio test for variance components does
      not follow a chi2 distribution with degrees of freedom equal to the number of
      parameters tested when the null hypothesis is true. Instead, the distribution of
      the likelihood ratio test is a mixture of chi2 distributions with different
      degrees of freedom. Implications for testing variance components in twin designs
      and for quantitative trait loci mapping are discussed. The appropriate
      distribution of the likelihood ratio test statistic should be used in hypothesis
      testing and model selection.

PMID- 16899156
TI  - Identification of twin pairs from large population-based samples.
AB  - The basis of most twin studies is the ascertainment of twins, often through twin
      registries, and determination of zygosity. The current rate of twin births in
      many industrialized countries implies that in the near future around 3% or more
      of individuals will be a twin. Hence, there are and will be a lot of twins around
      and many of those will not participate in twin studies. However, if large
      population-based samples are available that include appropriate identifiers, then
      twins can be detected and twin studies performed, even in the absence of zygosity
      information. We quantified the number of twin pairs that could be detected from a
      longitudinal survey in the Netherlands, which aims to answer questions about
      educational strategies and performance in primary education in the Netherlands.
      We detected 2865 twin pairs if we used a coded name identifier, date of birth,
      school, grade and year of survey, which is 2.01% of 284,945 pupils in five
      cohorts. Relaxing our selection criteria increased the number of apparent twin
      pairs identified, most of which are false positives due to chance matching of
      identification criteria. We show that the intraclass correlation on measured
      phenotypes can be used as a quality control measure for twin identification, and
      quantify the proportion of false negatives (true twin pairs not identified) due
      to missing data and data coding errors. We compared our estimated rate of twins
      in the sample to census data and estimate that with our most stringent selection
      criteria we detect more than 80% of all twin pairs in the sample. We conclude
      that the identification of twin pairs from large population-based samples is
      feasible, rapid and accurate if the appropriate identifiers are available, and
      that twin pairs from such sources are a valuable resource for studies to answer
      scientific question about twins versus nontwins and about genetic and
      environmental factors of twin resemblance.

PMID- 16899157
TI  - High microsatellite and SNP genotyping success rates established in a large
      number of genomic DNA samples extracted from mouth swabs and genotypes.
AB  - In this article, we present the genomic DNA yield and the microsatellite and
      single nucleotide polymorphism (SNP) genotyping success rates of genomic DNA
      extracted from a large number of mouth swab samples. In total, the median yield
      and quality was determined in 714 individuals and the success rates in 378,480
      genotypings of 915 individuals. The median yield of genomic DNA per mouth swab
      was 4.1 microg (range 0.1-42.2 microg) and was not reduced when mouth swabs were
      stored for at least 21 months prior to extraction. A maximum of 20 mouth swabs is
      collected per participant. Mouth swab samples showed in, respectively, 89% for
      390 microsatellites and 99% for 24 SNPs a genotyping success rate higher than
      75%. A very low success rate of genotyping (0%-10%) was obtained for 3.2% of the
      915 mouth swab samples using microsatellite markers. Only 0.005% of the mouth
      swab samples showed a genotyping success rate lower than 75% (range 58%-71%)
      using SNPs. Our results show that mouth swabs can be easily collected, stored by
      our conditions for months prior to DNA extraction and result in high yield and
      high-quality DNA appropriate for genotyping with high success rate including
      whole genome searches using microsatellites or SNPs.

PMID- 16899158
TI  - The latent class structure of ADHD is stable across informants.
AB  - Previous studies have looked at the structure of attention-deficit/hyperactivity
      disorder (ADHD) using latent class analysis (LCA) of Child Behavior Checklist
      (CBCL) or Diagnostic and Statistical Manual of Mental Disorders (DSM) symptom
      structure. These studies have identified distinct classes of children with
      inattentive, hyperactive, or combined subtypes and have used these classes to
      refine genetic analyses. The objective of the current report is to determine if
      the latent class structure of ADHD subtypes is consistent across informant using
      the Conners' Rating Scales (CRS). LCA was applied to CRS forms from mother,
      father, and teacher reports of 1837, 1329 and 1048 latency aged Dutch twins,
      respectively. The optimal solution for boys was a 5-class solution for mothers, a
      3-class solution for fathers, and a 4-class solution for teachers. For girls, a 4
      class solution for mothers and a 3-class for fathers and teachers was optimal.
      Children placed into a class by one informant had markedly increased odds ratio
      of being placed into the same or similar class by the other informants. Results
      from LCA using Dutch twins with the CRS show stability across informants
      suggesting that more stable phenotypes may be accessible for genotyping using a
      multi-informant approach.

PMID- 16899159
TI  - Subtypes of illicit drug users: a latent class analysis of data from an
      Australian twin sample.
AB  - This article applies methods of latent class analysis (LCA) to data on lifetime
      illicit drug use in order to determine whether qualitatively distinct classes of
      illicit drug users can be identified. Self-report data on lifetime illicit drug
      use (cannabis, stimulants, hallucinogens, sedatives, inhalants, cocaine, opioids
      and solvents) collected from a sample of 6265 Australian twins (average age 30
      years) were analyzed using LCA. Rates of childhood sexual and physical abuse,
      lifetime alcohol and tobacco dependence, symptoms of illicit drug
      abuse/dependence and psychiatric comorbidity were compared across classes using
      multinomial logistic regression. LCA identified a 5-class model: Class 1 (68.5%)
      had low risks of the use of all drugs except cannabis; Class 2 (17.8%) had
      moderate risks of the use of all drugs; Class 3 (6.6%) had high rates of cocaine,
      other stimulant and hallucinogen use but lower risks for the use of sedatives or
      opioids. Conversely, Class 4 (3.0%) had relatively low risks of cocaine, other
      stimulant or hallucinogen use but high rates of sedative and opioid use. Finally,
      Class 5 (4.2%) had uniformly high probabilities for the use of all drugs. Rates
      of psychiatric comorbidity were highest in the polydrug class although the
      sedative/opioid class had elevated rates of depression/suicidal behaviors and
      exposure to childhood abuse. Aggregation of population-level data may obscure
      important subgroup differences in patterns of illicit drug use and psychiatric
      comorbidity. Further exploration of a 'self-medicating' subgroup is needed.

PMID- 16899160
TI  - Association study of the dystrobrevin-binding gene with schizophrenia in
      Australian and Indian samples.
AB  - Numerous studies have reported association between variants in the dystrobrevin
      binding protein 1 (dysbindin) gene (DTNBP1) and schizophrenia. However, the
      pattern of results is complex and to date, no specific risk marker or haplotype
      has been consistently identified. The number of single nucleotide polymorphisms
      (SNPs) tested in these studies has ranged from 5 to 20. We attempted to replicate
      previous findings by testing 16 SNPs in samples of 41 Australian pedigrees, 194
      Australian cases and 180 controls, and 197 Indian pedigrees. No globally
      significant evidence for association was observed in any sample, despite power
      calculations indicating sufficient power to replicate several previous findings.
      Possible explanations for our results include sample differences in background
      linkage disequilibrium and/or risk allele effect size, the presence of multiple
      risk alleles upon different haplotypes, or the presence of a single risk allele
      upon multiple haplotypes. Some previous associations may also represent false
      positives. Examination of Caucasian HapMap phase II genotype data spanning the
      DTNBP1 region indicates upwards of 40 SNPs are required to satisfactorily assess
      all nonredundant variation within DTNBP1 and its potential regulatory regions for
      association with schizophrenia. More comprehensive studies in multiple samples
      will be required to determine whether specific DTNBP1 variants function as risk
      factors for schizophrenia.

PMID- 16899161
TI  - Twins of mistaken zygosity (TOMZ): evidence for genetic contributions to dietary
      patterns and physiologic traits.
AB  - Twin designs, comparing correlations in monozygotic (MZ) versus dizygotic (DZ)
      twins, have an extensive history. One major confounder in such studies is that MZ
      twins may share postnatal environmental influences more so than do DZ twins. To
      avoid such confounding, twins separated at or soon after birth have been studied,
      but their scarcity often makes this approach impractical. Another method has been
      to measure the degree of contact twins have maintained over time, and adjust the
      observed correlations. Here, we remove confounding by utilizing the discrepancy
      between biological and self-perceived zygosity to separate environmental from
      genetic sources of twin similarity. We analyzed dietary patterns and physiologic
      traits in 350 female twin pairs of the 1988 Kaiser Permanente Twin Registry.
      Among twin pairs, 175 were MZ by self-report and genetic testing (MZC), 136 were
      DZ by self-report and genetic testing (DZC), 30 were MZ by genetic testing but
      not by self-report (MZW), and 9 were DZ by genetic testing but not by self-report
      (DZW) but were excluded due to small sample size. For healthy food patterns, MZC
      and MZW intraclass correlations were similar and greater than for DZC, yielding
      positive and significant heritability estimates. For unhealthy food patterns, the
      MZC, MZW and DZC correlations were similar with no significant heritability. For
      physiologic traits, MZC and MZW correlations were similar and higher than those
      for DZC, indicating significant heritability, except for insulin for which MZW
      and DZC were similar and which showed modest heritability. Twins of mistaken
      zygosity (TOMZ) provides a useful approach to robust determination of
      heritability.

PMID- 16899162
TI  - Longitudinal genetic analysis of plasma lipids.
AB  - The consensus from published studies is that plasma lipids are each influenced by
      genetic factors, and that this contributes to genetic variation in risk of
      cardiovascular disease. Heritability estimates for lipids and lipoproteins are in
      the range .48 to .87, when measured once per study participant. However, this
      ignores the confounding effects of biological variation measurement error and
      ageing, and a truer assessment of genetic effects on cardiovascular risk may be
      obtained from analysis of longitudinal twin or family data. We have analyzed
      information on plasma high-density lipoprotein (HDL) and low-density lipoprotein
      (LDL) cholesterol, and triglycerides, from 415 adult twins who provided blood on
      two to five occasions over 10 to 17 years. Multivariate modeling of genetic and
      environmental contributions to variation within and across occasions was used to
      assess the extent to which genetic and environmental factors have long-term
      effects on plasma lipids. Results indicated that more than one genetic factor
      influenced HDL and LDL components of cholesterol, and triglycerides over time in
      all studies. Nonshared environmental factors did not have significant long-term
      effects except for HDL. We conclude that when heritability of lipid risk factors
      is estimated on only one occasion, the existence of biological variation and
      measurement errors leads to underestimation of the importance of genetic factors
      as a cause of variation in long-term risk within the population. In addition our
      data suggest that different genes may affect the risk profile at different ages.

PMID- 16899163
TI  - Heritability of testosterone levels in 12-year-old twins and its relation to
      pubertal development.
AB  - The aim of this study was to estimate the heritability of variation in
      testosterone levels in 12-year-old children, and to explore the overlap in
      genetic and environmental influences on circulating testosterone levels and
      androgen-dependent pubertal development. Midday salivary testosterone samples
      were collected on 2 consecutive days in a sample of 183 unselected twin pairs.
      Androgen-induced pubertal development was assessed using self-report Tanner
      scales of pubic hair development (boys and girls) and genital development (boys).
      A significant contribution of genetic effects to the variance in testosterone
      levels was found. Heritability was approximately 50% in both boys and girls. The
      remaining proportion of the variance in testosterone levels could be explained by
      nonshared environmental influences. The relatively high correlation between
      testosterone levels of opposite-sex dizygotic twins suggests that sex differences
      in genes influencing variation in testosterone levels have not yet developed in
      pre- and early puberty. Variance in pubertal development was explained by a large
      genetic component, moderate shared environmental influences, and a small
      nonshared environmental effect. Testosterone levels correlated moderately (r =
      .31) with pubertal development; the covariance between testosterone levels and
      pubertal development was entirely accounted for by genetic influences.

PMID- 16899164
TI  - Refractive errors in twin studies.
AB  - It is estimated that 1.6 billion people worldwide have myopia, a refractive
      error, and this number is expected to increase to approximately 2.5 billion by
      the year 2020. It is now well established that both the environment and genetics
      play a role in the development of myopia. However, the exact contribution of each
      of these components to myopia development has yet to be completely determined.
      Twin studies (classical twin model) are commonly used to determine the weighting
      of genetic and environmental components in disease. Over the last century, twin
      studies have investigated the heritability of refractive errors in different
      sample populations and have collectively supported a genetic basis to refractive
      errors. However, different sample populations and methods of data collection have
      produced a wide range of heritability estimates ranging from .5 to .9. This
      article will review those twin studies that have investigated refractive error,
      particularly myopia, as well as biometric measures linked to refractive error, to
      compare heritability estimates and methodology designs.

PMID- 16899165
TI  - Familial risks for diseases of myoneural junction and muscle in siblings based on
      hospitalizations and deaths in sweden.
AB  - Diseases of the myoneural junction and muscle are disabling and some are life
      threatening. Recent successes in the identification of the underlying genetic
      mechanisms have had profound implication for their diagnostics, treatment and
      classification. We define familial risks for siblings who were hospitalized for
      or deceased from diseases of the myoneural junction and muscle. A nationwide
      database on diseases of the myoneural junction and muscle was constructed by
      linking the Multigeneration Register on 0- to 69-year-old siblings to the
      Hospital Discharge Register and the Causes of Death Register from years 1987 to
      2001. Standardized risk ratios (SIRs) were calculated for affected sibling pairs
      by comparing to those whose siblings had no diseases of myoneural junction and
      muscle. Among a total of 2307 patients, myasthenia gravis, muscular dystrophy and
      myotonic disorders were commonest diagnoses. The sibling risks for these disease
      were 22, 190 and 198, respectively, when a sibling was diagnosed with any disease
      of the myoneural junction and muscle. The concordant SIRs, both siblings
      presenting the same disease, were 42 for myasthenia gravis, 737 for muscular
      dystrophy, 2000 for congenital myopathy, 1211 for myotonic disorder, 909 for
      periodic paralysis and 209 for unspecified myopathy. Only a few discordant
      sibling pairs were noted. The very high overall SIRs for the diseases of the
      myoneural junction and muscle imply that the sporadic forms of these diseases are
      relatively rare and these diseases are overwhelmingly heritable.

PMID- 16899166
TI  - Familial risks for main neurological diseases in siblings based on
      hospitalizations in Sweden.
AB  - Recent successes in identifying the underlying genetic mechanisms for
      neurological diseases, particularly for their Mendelian forms, have had profound
      implications for their diagnostics, treatment and classification. However, there
      has never been an attempt to compare familial risks in a systematic way among and
      between the main neurological diseases. Familial risks were here defined for
      siblings who were hospitalized because of a neurological disease in Sweden. A
      nationwide database for neurological diseases was constructed by linking the
      Multigeneration Register of 0- to 69-year-old siblings to the Hospital Discharge
      Register for the years 1987 to 2001. Standardized risk ratios were calculated for
      affected sibling pairs by comparing them to those whose siblings had no
      neurological disease. There were three main results. First, it was shown that all
      disease groups had a familial risk, with the exception of transient ischemic
      attacks, and the risks could be ranked from the highest (3451) for Huntington's
      disease to the lowest (2.1) for inflammatory diseases. Second, increased familial
      risks were shown for disease subtypes for which susceptibility genes or familial
      clustering have not been demonstrated previously, including multiple sclerosis,
      sleep apnea, nerve, nerve root and plexus disorders, and cerebral palsy. Third,
      based on the available sample size there was no convincing evidence for familial
      comorbidity between the disease groups, suggesting that the factors causing
      familial aggregation, probably usually heritable genes, are distinct for each
      subtype. The high familial risks for neurological disease imply heritable
      etiology and opportunities for identification of further susceptibility genes.

PMID- 16899167
TI  - Fetal death registration in multiple births: anomalies and clinical significance.
AB  - Trends in the civil registration of fetal death in multiple gestations that has
      occurred before, but expelled from the womb after, 24 weeks' gestation are
      examined using England and Wales 1993-2004 registration obtained from the Office
      for National Statistics. Count was made of fetal death registrations in which
      fetus papyraceous, fetal death before 24 weeks' gestation or fetocide before 24
      weeks' gestation was recorded. There were 3700 fetal death registrations among
      217,595 twin, triplet and higher order multiple births in England and Wales
      between 1993 and 2004. In 354 (9.6%) of these fetal deaths, death was recorded as
      having occurred before 24 weeks' gestation. There has been a three-fold increase
      in such fetal death registrations. It is a legal requirement of parents to
      register a fetal death. The definition of a fetal death that meets formal
      registration criteria is that the fetus is expelled from the womb after 24 weeks'
      gestation. However, if the fetal death occurs before 24 weeks, there is
      confusion, nationally and internationally, whether or not registration is legally
      required. Fetal death in a multiple gestation has serious clinical implications
      for a surviving co-conceptus and failure to inform parents of an early death in a
      multiple gestation may have important repercussions. Legal definition for the
      registration of fetal death requires international agreement and application.

PMID- 16899168
TI  - Factors influencing the stillbirth rates in single and multiple births in Sweden,
      1869 to 1967.
AB  - Temporal variations in the stillbirth rate among singletons, twins and triplets
      in Sweden between 1869 and 1967 were studied. Both among single and multiple
      births there were marked secular decreasing trends in the stillbirth rates. Based
      on our long time series since 1869, this study confirms that among twins and
      triplets the stillbirth rate was higher among same-sexed than among opposite
      sexed sets. Comparisons between the stillbirth rates among twin births in urban
      and rural regions indicate higher stillbirth rates in rural areas. In addition,
      the stillbirth rates among twins of unmarried mothers were higher than those of
      twins of married mothers. These findings also hold for both same-sexed and
      opposite-sexed twin pairs. Analyses of the stillbirth rates for singletons and
      for different types of twins indicate that up to 1950 the risk of stillbirth
      among males was almost constantly between 15% to 20% higher than among females.
      After that the difference in the risk decreased. Comparisons with other
      populations were performed.

PMID- 16899169
TI  - Cantrell's Pentalogy in Twins: Prenatal Diagnosis.
AB  - The combination of an onphalocele, an anterior thoracic wall defect and an
      anterior diaphragmatic defect constitutes classical Cantrell's pentalogy. We
      present a case of Cantrell's pentalogy diagnosed prenataly in twins with
      conventional and three-dimensional sonography.

PMID- 16899170
TI  - Empirical evaluation of the genetic similarity of samples from twin registries in
      Australia and the Netherlands using 359 STRP markers.
AB  - One way to achieve the large sample sizes required for genetic studies of complex
      traits is to combine samples collected by different groups. It is not often
      clear, however, whether this practice is reasonable from a genetic perspective.
      To assess the comparability of samples from the Australian and the Netherlands
      twin studies, we estimated Fst (the proportion of total genetic variability
      attributable to genetic differences between cohorts) based on 359 short tandem
      repeat polymorphisms in 1068 individuals. Fst was estimated to be 0.30% between
      the Australian and the Netherlands cohorts, a smaller value than between many
      European groups. We conclude that it is reasonable to combine the Australian and
      the Netherlands samples for joint genetic analyses.

PMID- 16899171
TI  - Response to Puts and Dawood's 'the evolution of female orgasm: adaptation or
      byproduct?'--Been there.
AB  - David Puts and Khytam Dawood's recent critique of my book, The Case of the Female
      Orgasm: Bias in the Science of Evolution, attempts to make plausible an adaptive
      account of female orgasm based on a hypothesized mechanism of uterine upsuck and
      sperm competition. Yet the authors fail to respond to the criticisms of such
      accounts that I detailed previously in my book. They raise a further concern
      about my definition of adaptation--a red herring--and manufacture a conceptual
      error regarding heritability that they then attribute to me. Most seriously, they
      fail to address the glaring failure of sperm competition accounts to accord with
      evidence from sexology. Specifically, the distribution curve of orgasm-with
      intercourse--according to Dawood et al.'s own data, as well as others'--is
      relatively flat across the various classes. This curve needs to be tested against
      a well-formed multistrategy adaptive hypothesis; it cannot be explained by the
      adaptive account defended by Puts and Dawood in their critique.

PMID- 16899172
TI  - SuperQuads: a day in the life; research reviews: color-number association, finger
      length ratios, twinning diets, athletic pairs.
AB  - The nature and frequency of quadruplet births are reviewed, followed by a close
      up look at the 6-year-old monozygotic Mathias quadruplets. This essay is followed
      by reviews of new twin research on color-number association, male-female twins'
      finger-length ratios, and links between twinning and dietary practices. The
      article finishes by focusing on unusual twin athletes in football, basketball and
      golf, and on twin co-authors of a new book on the 1972 silver medal victory by
      the United States hockey team.

PMID- 16899174
TI  - Collaborated basic bio-medical research.

PMID- 16899175
TI  - Cardiac myxomas--clinical spectrum and outcome.
AB  - OBJECTIVE: To describe the characteristics and outcome of patients with cardiac
      myxomas. DESIGN: A case series. PLACE AND DURATION OF STUDY: The Aga Khan
      University Hospital (AKUH), from 1999 to 2004. PATIENTS AND METHODS: All patients
      diagnosed and managed as having cardiac myxomas at AKUH, during a period of six
      years (1999-2004) were included. Data was collected by reviewing clinical
      records. Follow-up data was collected from the clinical records and by a
      telephone interview where required. RESULTS: Out of 15 patients who were
      diagnosed to have cardiac myxomas, complete information was available in 14
      patients. There was a female predominance (64%) with a mean age of 47 years.
      About two-thirds (71%) had symptom of dyspnoea. Half of the patients (50%) had
      neurological symptoms at presentation. Constitutional symptoms were present in
      36% of patients. About two-third of patients (71%) had positive findings on
      cardiac auscultation. None of the patients had any rhythm abnormalities on the
      ECG. Diagnosis was made by transthoracic echocardiography in all patients. All of
      the tumors were located in the left atrium, and majority (64%) were attached to
      the interatrial septum. All patients were advised surgical treatment, however,
      only 8 (57%) were operated upon. Outcome was good in those who were operated
      upon, with no peri and postoperative mortality. CONCLUSIONS: Cardiac myxomas are
      a rare, but potentially curable form of heart disease. They occur in a wide range
      of age groups with a female predominance. Dyspnea is the most common clinical
      feature followed by embolic complications. Left atrium is the most common site of
      location. Surgical excision is a safe and effective procedure.

PMID- 16899177
TI  - Complications / problems of colostomy in infants and children.
AB  - OBJECTIVE: To determine the frequency of complications/problems occurring with
      construction of colostomy in infants and children. DESIGN: Descriptive study.
      PLACE AND DURATION OF STUDY: Surgical Unit B, National Institute of Child Health,
      Karachi, from September 2001 to March 2003. PATIENTS AND METHODS: All the
      patients admitted in the unit who required colostomy as part of their management
      were included in the study. The patients who were operated upon previously or
      operated elsewhere and referred after having colostomy, were excluded. Problems
      associated with colostomy construction like skin excoriation and chronic blood
      loss were also recorded. Chi-square test of proportion was used to determine the
      p-value. RESULTS: There were 121 patients. Most of the patients were operated due
      to anorectal malformations (n=71) and Hirschsprung's disease (41).
      Complications/problems related to colostomy occurred in 67.7% patients. The most
      common problem was skin excoriation. Second in rating was chronic blood loss from
      stoma. Prolapse of stoma was more common in transverse loop colostomies. Divided
      colostomies had higher number of complications as compared to loop colostomies,
      similarly, transverse colostomies had high number of complications but in both
      the cases difference was not statistically significant. Four (3.3%) patients
      died. CONCLUSION: Construction of colostomy in paediatric patients carries high
      frequency of complications/problems and requires careful technique. The role of
      stoma care clinic and enterostomal therapist can be instrumental in preventing
      problems associated with colostomy.

PMID- 16899176
TI  - Gated spect myocardial perfusion scintigraphy for identifying septal perfusion
      artifacts in left bundle branch block.
AB  - OBJECTIVE: To determine the role of gated Single Photon Emission Computed
      Tomography (SPECT) for accurate assessment of myocardial perfusion scintigraphy
      (MPS) of patients with left bundle branch block (LBBB). DESIGN: Analytical study.
      PLACE AND DURATION OF STUDY: Punjab Institute of Nuclear Medicine (PINUM),
      Faisalabad, Pakistan, from June 2002 to April 2003. PATIENTS AND METHODS: MPS
      data of patients with LBBB was analyzed. Resting gated SPECT MPS was performed
      after an injection of 740 MBq 99mTc-MIBI in 10 normal and 25 subjects with LBBB
      (with low probability of coronary artery disease). Visual and quantitative
      analyses were done on non-gated (NG), end diastolic (ED), end systolic (ES)
      images. Calculations included septal to lateral wall ratio (SLR), myocardial
      thickening (MT=% increase in counts during systole) at end systolic phase and
      myocardial thickening at peak level (% peak MT). RESULTS: Septal hypoperfusion
      was noted in 19 (76%) patients on NG images and in only 1 (4%) patient on gated
      SPECT ED images. On NG images of LBBB group, SLR was lower than in controls
      (0.68+/-0.07 vs. 0.87+/-0.05, p<0.001). SLR of LBBB patients approached to that
      of control group in gated SPECT ED data (0.86+/-0.06 vs 0.88+/-0.06, p=ns).
      Myocardial thickening at ES for septum was markedly lower in LBBB group than in
      controls (21.83%+/-10.86 vs. 66.32%+/-20.15, p<0.001). CONCLUSION: In patients
      with LBBB, reduced septal thickening results in artifactual septal perfusion
      defects. Gating the perfusion scintigraphy and reporting perfusion status on end
      diastolic frames in LBBB patients can eliminate these artifacts.

PMID- 16899178
TI  - Frequency and pattern of urinary complaints among pregnant women.
AB  - OBJECTIVE: To determine the frequency pattern of presentation and causative
      agents of lower urinary tract symptoms in pregnant females. DESIGN: Descriptive
      study. PLACE AND DURATION OF STUDY: Department of Obstetrics and Gynaecology,
      Fatima Memorial Hospital, Lahore, from January 2003 to May 2003. PATIENTS AND
      METHODS: One thousand consecutive pregnant women, attending the antenatal clinics
      of Fatima Memorial Hospital, were included in the study. Women with renal
      pathology, postrenal transplant and those on immunosuppressive agents were
      excluded. All women underwent complete examination of urine. Those who had one or
      more urinary complaints had culture and sensitivity test of urine. Other
      variables studied were the symptomatology. RESULTS: Out of one thousand pregnant
      women, 426 (42.6%) complained of one or more urinary symptoms. Diurnal and
      nocturnal frequency was the most commonly encountered symptom (87.32%), followed
      by irritative symptoms and voiding difficulties. Complete urine examination of
      symptomatic patients revealed<5 pus cells /HPF (high power field) in 322 cases
      and 6-20 pus cell/HPF in the remaining 104 cases. The urine culture of the
      symptomatic patients (426 cases) showed growth in only 37 cases (8.69%).
      Escherichia (E.) coli was the commonest organism (89.1%) followed by
      Staphylococcus (S.) aureus (8.1%) and candidiasis (2.7%). CONCLUSION: Lower
      urinary tract symptoms are frequently present in pregnant women, which can be due
      to both pregnancy-induced changes on urinary system as well as urinary infection.
      It is important to differentiate between the two because former requires only
      reassurance whereas the latter needs antibiotic treatment.

PMID- 16899179
TI  - Kirschner wire pin tract infection rates between percutaneous and buried wires in
      treating metacarpal and phalangeal fractures.
AB  - OBJECTIVE: To compare pin tract infection rate between percutaneous and buried
      placement of Kirschner (K-) wiring for hand fractures. STUDY DESIGN: Quasi-
      experimental study. PLACE AND DURATION: Plastic, Reconstructive, Hand and Burn
      Surgery Unit, Liaquat National Hospital, Karachi, from September 2005--February
      2006. PATIENTS AND METHODS: Patients with fractures of metacarpals and phalanges
      of hand were selected by non-probability purposive method. Assessment of pin
      tract infection by clinical examination and pin tract scoring was done by
      modification of Oppenheim classification. Statistical analysis was done using Chi
      square test. RESULTS: Ten out of 55 percutaneous and 2 out of 45 buried wires
      were infected. The difference in infection rates of two groups was statistically
      significant at p<0.05. Three percutaneous, but not buried Kirschner wires, had to
      be removed before 4 weeks because of failure to respond to local wound care and
      oral antibiotics. CONCLUSION: Percutaneous K- wires had significantly greater
      infection rate than wires which were buried deep to the skin.

PMID- 16899180
TI  - Wilms' tumour: a comparison of surgical aspects in patients with or without pre
      operative chemotherapy.
AB  - OBJECTIVE: To compare the technical aspects of Wilms' tumour (WT) surgery in
      patients with and without pre-operative chemotherapy. DESIGN: Quasi-experimental.
      PLACE AND DURATION OF STUDY: Military Hospital (MH) and Combined Military
      Hospital (CMH), Rawalpindi, from January 1999 to December 2004. PATIENTS AND
      METHODS: Patients of WT, presenting between January 1999 and December 2001, were
      treated, using the NWTSG protocol, with primary surgery (group I). Between
      January 2001 and December 2004, WT patients were treated according to SIOP
      protocol, with pre-operative chemotherapy followed by surgery (group II). Volume
      reduction with chemotherapy, duration of surgery, rupture of tumour, extent of
      excision, adherence and damage to surrounding structures, blood loss,
      complications, stay in hospital and event-free survival (EFS) were compared in
      the two groups. RESULTS: Out of 22 patients in group I, 19 (86.4%) underwent
      primary surgery. Of the 23 patients in group II, 21 (91.3%) received pre
      operative chemotherapy followed by surgery. Average volume reduction in this
      group was 54% with chemotherapy. Difference in duration of surgery and blood loss
      was significantly low in group II (p=0.003 and p < 0.001, respectively). In group
      I, rupture (6 vs 2), adherence (14 vs 10) and damage to surrounding structures (5
      vs 2) were more. Complete macroscopic excision was possible in 90.5% of WT in
      group II as compared to 73.7% in group I. Immediate postoperative complications
      and length of hospital stay were similar in both groups. There was no difference
      in EFS. CONCLUSION: Pre-operative chemotherapy makes it technically easier and
      safer to operate, without jeopardizing the final outcome.

PMID- 16899182
TI  - Effect of weaning period on nutritional status of children.
AB  - OBJECTIVE: To determine the effect of age of introduction and the type of weaning
      foods used, on the nutritional status of children under three years of age.
      DESIGN: Cross-sectional, community-based study. PLACE AND DURATION OF STUDY: The
      study was conducted in rural areas of District Malir in Karachi, Pakistan,
      comprising of 900 villages spread over 1200 square kilometer, from November 2000
      to April 2001. PATIENTS AND METHODS: Three hundred and fifty-nine children under
      3 years were included in the study. Based on the age of commencement of weaning,
      the children were categorized as children weaned at appropriate and inappropriate
      age. For the type of weaning foods, the children were grouped into two categories
      based on the nature of food items. RESULTS: Children for whom weaning was started
      at the recommended age of 4-6 months were found to be significantly less
      malnourished on anthropometric measurements as compared to the other set in which
      weaning was started at an earlier or later age. Significant statistical
      difference was noted in the children weaned on nutritious home-made items
      compared to children having commercial foods. CONCLUSION: Malnutrition is of
      multi-faceted origin beyond only poverty and food shortage. Inappropriate feeding
      practices can result in growth faltering as noted in the present study.
      Programmes should be launched for education of mothers regarding weaning
      practices.

PMID- 16899181
TI  - Lumbar puncture in neonates under and over 72 hours of age.
AB  - OBJECTIVE: To identify the criteria for performing a spinal tap in neonates with
      suspected sepsis and compare the findings in infants under and over the age of 72
      hours. STUDY DESIGN: Analytical. PLACE AND DURATION: Neonatal Ward of Taleghani
      Medical Centre, Shaheed Beheshti University of Medical Sciences, Evin,Tehran.
      Study period was of one year, from March 2003 to February 2004. PATIENTS AND
      METHODS: All newborns subjected to a lumbar puncture during the first 24 hours of
      admission were enrolled in the study. Results of cerebrospinal fluid analysis
      were scrutinized. RESULTS: There were 380 neonates in the study. Majority i.e.
      248 infants were aged<72 hours. Meningitis was diagnosed in 22 cases, (5.8%).
      There was no significant difference in the incidence of meningitis between
      neonates under and over 72 hours of age, (6.9% vs. 3.8%, p-value>0.5). Comparison
      of risk factors, clinical manifestations, and routine laboratory investigations
      revealed no significant difference in babies with or without meningitis.
      CONCLUSION: The findings of this series do not support a selective approach for
      performing a lumbar puncture in a possibly septic newborn. A lumbar puncture is
      recommended in all neonates with suspected sepsis regardless of age, risk
      factors, or specific neurological manifestations.

PMID- 16899184
TI  - Intra-cardiac Burkitt's lymphoma mimicking acute pulmonary embolism.
AB  - Primary cardiac lymphoma is a rare clinical entity with poor prognosis and
      delayed diagnosis is often due to variable and non-specific clinical
      presentation. The case of an elderly male is reported with multiple co
      morbidities, who had undergone a spinal laminectomy two weeks prior to
      presentation, later presented to the emergency room (E.R.) with acute chest pain,
      dyspnea and hypoxemia. A diagnosis of intracardiac thrombus was made, based on
      the clinical picture and echocardiography findings but per-operatively, he was
      found to have an extensive, non-resectable cardiac tumor.

PMID- 16899183
TI  - Complications of inguinal hernia surgery in children.
AB  - OBJECTIVE: To determine the postoperative complications of elective inguinal
      hernia surgery in children DESIGN: Descriptive study. PLACE AND DURATION OF
      STUDY: Surgical Unit B, National Institute of Child Health, Karachi, from
      February 2004 to November 2005. PATIENTS AND METHODS: Children with inguinal
      hernia, admitted electively through surgical outpatient, were included. Patients
      operated earlier and presenting with complications were excluded. Patients with
      concomitant diseases, regarded as predisposing factors for hernia development,
      were also excluded. Physical examination and relevant investigations (hemoglobin
      level and ultrasound of scrotum) were performed. Inguinal hernia was repaired
      electively by Rehbein procedure. Patients were followed at day 7, 1 month, 3
      months and 9 months to note the postoperative complications of the surgery.
      Ultrasound was repeated at 6 and 9 months postoperatively for the size of testes.
      RESULTS: A total of 223 patients with inguinal hernia were included in the study.
      Age ranged from 8 days to 12 years. There were 188 males with 75 patients under 1
      year of age. The longest follow-up was upto 9 months in 133 patients. The
      complications of scrotal edema occurred in 6 (2.97%), haematoma in 1(0.49%),
      wound infection in 2 (0.99%) and 5 events of recurrence of hernia in 4 patients.
      All appeared within 3 months of follow-up. Four recurrent hernia were operated.
      In all cases intact sac was found. No patient developed decrease in size of
      testes nor ascent of testes was noted at follow-up. CONCLUSION: in this series,
      there were minimal complications observed in relation to inguinal hernia surgery.

PMID- 16899185
TI  - Synchronous bilateral testicular tumors.
AB  - Synchronous bilateral testicular tumors are a rare entity. One such case of an
      elderly male is reported who presented with bilateral painless testicular
      swellings of 3 months duration. After clinical workup, provisional diagnosis of
      bilateral testicular tumors was made and bilateral orchidectomy was performed.
      Histopathology report revealed bilateral seminoma.

PMID- 16899186
TI  - Coexistence of caseating granulomas with Hodgkin's lymphoma: a diagnostic and
      clinical dilemma.
AB  - Hodgkin's lymphoma (HL) is a neoplasm of the B lymphocytes. The histological
      picture may resemble granulomatous lesions similar to those seen in tuberculosis
      as collections of epitheloid cells are not uncommonly seen in HL. In areas which
      are endemic to tuberculosis, the close association and the coexistence of the two
      must be recognized for the proper diagnosis and treatment of the illness. A
      series of cases of Hodgkin's lymphoma is reported in which the biopsy specimens
      from different parts of the body portrayed caseating granulomatous lesions.

PMID- 16899187
TI  - Bilateral parietal extradural metastatic Ewing's sarcoma simulating acute
      epidural hematoma.
AB  - Sarcomas usually metastasize to lungs. The following case report describes an
      unusual metastasis of Ewing's sarcoma to extradural parietal region bilaterally.
      The primary was found at lower end of ulna.

PMID- 16899188
TI  - Hallervoredn-Spatz disease.
AB  - Hallervorden-Spatz disease is an extremely rare cause of dystonia that carries a
      poor prognosis. A case occurring in an 11-year-old girl with progressive extra
      pyramidal symptoms since infancy is described. The clinical picture and typical
      radiological findings are described.

PMID- 16899189
TI  - Neonatal Bartter syndrome.
AB  - A pre-term baby girl was born following a pregnancy complicated by severe
      polyhydramnios at a gestational age of 36 weeks. She was initially suffering from
      respiratory distress consistent with idiopathic respiratory distress syndrome,
      and altered electrolyte imbalance with hyponatremia, hypokalemia and
      hypochloremic metabolic alkalosis. However, during the third week of life when
      she had dehydration along with significant electrolyte imbalance, Bartter's
      syndrome was considered which was supported by findings of high renin and
      aldosterone levels. Treatment was done by correction of electrolytes and
      dehydration along with indomethacin. The drug was well tolerated. The infant
      showed correction of electrolyte imbalance. The features of this case suggest an
      extreme form of Bartter's syndrome presenting from the early days of life. The
      syndrome is reported because of it's rarity and alerts pediatricians to the
      antenatal and neonatal variant of Bartter's syndrome.

PMID- 16899190
TI  - Segmental defect of intestinal musculature: a rare cause of intestinal
      obstruction in children.
AB  - A 3 years old female child was brought to the emergency department with acute
      abdomen. Laparotomy disclosed multiple segmental dilatations in the middle third
      of the ileum which was resected and anastomosed. Post-operative recovery was
      uneventful. Histopathological findings showed lack of smooth and longitudinal
      muscles in dilated segments of the intestine with intact mucosa without any
      evidence of necrosis and inflammation.

PMID- 16899191
TI  - Acute limb ischemia due to ergotism.
AB  - Acute ischemia of an extremity potentially threatens limb loss and occasionally
      the life of the patient. We are reporting two cases of extremity ischemia
      secondary to ergot poisoning. The first patient was a 60 years old woman, who
      presented with a 15 days history of ischemia of the left arm with gangrene of the
      fingers and pain in the resting right hand for one day. Right brachial artery
      catheterization showed severe spasm of the artery which was resolved by passage
      of the inflated balloon catheter. She underwent amputation for gangrene of the
      left hand. The second patient presented with bilateral symmetrical ischemia of
      the lower extremities which improved upon withdrawal of the ergot containing
      medicine. She responded to nifedipine.

PMID- 16899192
TI  - Serotonergic modulation of dopamine neurotransmission: a mechanism for enhancing
      therapeutics in schizophrenia.
AB  - Although the principal mechanism by which all antipsychotic drugs act is the
      blockade of dopamine D-2 receptors, typical antipsychotics given in doses within
      the clinically effective range induce extrapyramidal symptoms (EPS). Serotonin
      Hydroxytryptamine, 5-HT can modulate the activity of dopaminergic neurons, while
      the activity of atypical antipsychotic agent towards serotonin receptors is
      involved in the ability of these agents to produce fewer EPS. In order to extend
      therapeutics in schizophrenia, it is important to examine the serotonergic
      modulation of neuroleptic activity. This review analyzes differences in
      neurochemical, behavioral and pharmacological profiles of typical and atypical
      antipsychotics and the role of serotonin receptors in the attenuation of EPS
      induced by the typical neuroleptics. In addition to blocking dopamine receptors,
      the atypical antipsychotics also have affinities for serotonin receptors.
      Serotonergic modulation of motor activity appears primarily of inhibitory type.
      Stimulation of somatodendritic 5-HT-1A receptors decreases the availability of 5
      HT at inhibitory 5-HT-2C receptors located on dopaminergic neurons to attenuate
      acute parkinsonian-like effects of typical antipsychotics. An increase in the
      effectiveness of pre and postsynaptic 5-HT-1A receptors following long-term
      administration of haloperidol raises the possibility that 5-HT agonists may also
      prove useful for the alleviation of late appearing tardive dyskinesias.
      Clinicians can now apply the knowledge of serotonergic modulation of neuroleptic
      action to the treatment of schizophrenic patients by using selected serotonergic
      anxiolytics and antidepressants as adjuvants in the treatment of schizophrenia.

PMID- 16899193
TI  - Complete androgen insensitivity syndrome in an X Y female.

PMID- 16899194
TI  - Non invasive prenatal determination of fetal rhesus d status from maternal
      plasma: need of the time for Pakistan.

PMID- 16899195
TI  - 5 year survival of a patient with malignant thymoma with superior vena caval
      syndrome.

PMID- 16899196
TI  - TACI mutation in common variable immunodeficiency and IgA deficiency.
AB  - Common variable immunodeficiency (CVID) is a heterogeneous primary
      immunodeficiency disease. Immunoglobulin A deficiency (IGAD) shares some
      clinical, laboratory, and genetic features with CVID and occurs with relatively
      greater frequency in first-degree relatives of individuals with CVID. Recently,
      patients with CVID and IGAD have been found to have mutations of the gene
      TNFRSF13B encoding the TACI (transmembrane activator and calcium-modulator and
      cyclophilin-ligand interactor), a member of the tumor necrosis factor-receptor
      superfamily. In this article, we review the various TACI mutations that have been
      identified so far. Although six mutations have been reported, no clear genotype
      phenotype association has been shown to date. This suggests that the phenotypic
      expression of TACI mutation is affected by additional genetic and environmental
      factors. Analysis of a larger sample of patients will be needed to determine if
      the specific mutations are associated with a particular phenotype or
      predisposition to the common features of CVID and IGAD: autoimmunity,
      lymphoproliferation, or malignancy.

PMID- 16899197
TI  - Interleukin-10-secreting regulatory T cells in allergy and asthma.
AB  - Allergic diseases, including asthma, are chronic inflammatory disorders
      originating from an aberrant immune response to innocuous antigens in our
      environment (allergens). In susceptible individuals, sensitization to allergen
      leads to the induction of allergen-specific T-helper type 2 (Th2) responses and
      immunoglobulin E (IgE) production. Subsequent challenge with allergen results in
      IgE-mediated mast cell activation and the recruitment and activation of effector
      cells, leading to clinical symptoms of disease. In this review, we discuss
      evidence that the anti-inflammatory cytokine interleukin-10 (IL-10) offers
      therapeutic promise for the control of asthma and allergy. We highlight the
      potential role of IL-10 secretion by a specialized T-cell subset, T regulatory
      cells, to prevent allergic inflammation in healthy individuals and to provide
      long-term relief from disease symptoms in allergic patients.

PMID- 16899198
TI  - Thymic stromal lymphopoietin:a potential therapeutic target for allergy and
      asthma.
AB  - Thymic stromal lymphopoietin (TSLP) is an interleukin (IL)-7-like cytokine that
      has recently been implicated as central to the microenvironment and is permissive
      for the immunologic cascade that initiates and propagates allergic immune
      responses. In humans, TSLP is produced predominantly by epithelial cells and
      activated mast cells, and stimulates myeloid dendritic cells (mDC), which
      uniquely express the heterodimeric TSLP receptor. TSLP-activated mDC can promote
      naive CD4+ T cells to differentiate into a Th2 phenotype and can promote the
      expansion of CD4+ Th2 memory cells. Recent evidence implicates TSLP as playing a
      pivotal role in the pathobiology of allergic asthma and atopic dermatitis. The
      potential for TSLP to provide a new therapeutic target for the treatment of
      allergic disorders is compelling, and elucidating the mechanisms that regulate
      TSLP expression and the effects of TSLP on orchestrating the immune response
      toward a Th2 phenotype should facilitate this quest.

PMID- 16899199
TI  - Mannan-binding lectin in asthma and allergy.
AB  - Mannan-binding lectin (MBL) is a vital and versatile component of innate
      immunity. It is present in serum and may bind to a plethora of microbial
      pathogens and mediate opsonization of these by complement-dependent and/or
      independent mechanisms. Low-MBL levels in serum, attributed to certain genetic
      polymorphisms, constitute a major factor predisposing to several infectious
      diseases. However, recent studies propose that MBL extends beyond its classic
      role as a first-line host-defense molecule to a modulator of inflammation. In
      this review, we summarize and explore this potential and a possible novel role of
      MBL in asthma and allergy.

PMID- 16899200
TI  - Immune dysregulation in atopic dermatitis.
AB  - Atopic dermatitis is a chronic inflammatory skin disease that causes significant
      morbidity in affected individuals. It is characterized by dysregulated immune
      responses that consist of an increased systemic Th2 response and a combination of
      Th2 and Th1 responses in the skin lesions. In this article, we review factors
      that contribute to these abnormal responses, including key effector cells of the
      immune system, chemokines, defective skin barrier, genetic predisposition, and
      environmental triggers. Understanding these pathomechanisms may improve our
      current therapies for atopic dermatitis.

PMID- 16899201
TI  - Update on toll-like receptor ligands and allergy: implications for immunotherapy.
AB  - Innate responses to microbes are mediated in large part via toll-like receptors
      (TLRs) that recognize a diverse family of ligands produced by viruses, bacteria,
      and fungi. Great effort has been directed toward translating this knowledge into
      the development of therapies for the prevention and treatment of diseases,
      including those fueled by allergic (Th2-biased) hypersensitivities. In this
      review, we consider the ways in which ligands for different TLRs influence the
      allergic phenotype. In addition, an update on safety and efficacy data from
      clinical trials of allergic patients treated with TLR9 ligand-based interventions
      is provided. Finally, recent experimental results that help elucidate how ambient
      TLR ligand exposures influence allergic risk and their relevance to the
      development of TLR ligand-based therapeutics are discussed. Investigations
      presented within this opinion paper suggest that several TLR ligands could have
      clinical utility in the treatment of allergic diseases, whereas other TLR ligands
      appear less attractive, as they facilitate development of Th2-biased
      hypersensitivities in murine studies.

PMID- 16899202
TI  - Evaluation of allergen vaccine potency.
AB  - The development of reliable and clinically relevant potency assays is essential
      to the practice of safe and effective allergen-specific immunotherapy. Allergen
      standardization in the United States is based on the establishment of a national
      reference assigned with a biological potency unit to which manufacturers'
      products are compared using validated relative potency assays. This ensures, at
      least with standardized allergen vaccines, comparability between lots used in
      clinical practice. Recent progress in the ability to measure the specific
      allergen content of allergen vaccines has led to its application in monitoring
      consistency and characterizing allergen preparations. More recently, the "major
      allergen" content of allergen vaccines has become a means to compare extracts
      from different manufacturers and to recommend immunotherapy dosing regimens. At
      the same time, qualitative differences exist between manufacturers' products, and
      most allergen vaccines used in clinical practice are nonstandardized. Therefore,
      this approach can be confusing and is misleading. The establishment of additional
      allergen reference standards and the development of reliable, accurate, and
      clinically relevant potency assays are urgently needed.

PMID- 16899203
TI  - New insights in sublingual immunotherapy.
AB  - Sublingual immunotherapy (SLIT) is accepted in the official documents and is
      currently used in many European countries. In recent years, new clinical data on
      efficacy and safety have been published, including meta-analyses in adults and
      children and surveys of safety in children younger than age 5 years. Moreover, it
      has been shown that, similar to the injection route, SLIT can prevent the onset
      of new sensitizations and the onset of asthma. Additionally, the mechanisms of
      action are beginning to be systematically studied. Some points need further
      investigation, such as the effect in asthma, the mechanisms of action, and the
      optimal dose to be administered.

PMID- 16899204
TI  - Mite immunotherapy.
AB  - Dermatophagoides pteronyssinus and D. farinae are the most common house dust
      mites and are among the most common sources of indoor allergens worldwide. These
      species are very common in humid regions, where most allergic individuals are
      sensitized to house dust mites. Specific immunotherapy with mite extracts has
      demonstrated clinical benefits in several double-blind, placebo-controlled trials
      that are included in recent reviews of subcutaneous immunotherapy, including
      pediatric and adult patients with rhinoconjunctivitis and or asthma. Most
      successful studies of mite immunotherapy have used native allergen extracts
      adsorbed onto aluminum hydroxide, or chemically modified mite-allergen extracts.
      Several studies have also shown efficacy using sublingual immunotherapy in
      pediatric and adult patients with asthma and/or rhinitis. Additionally, the
      efficacy of subcutaneous immunotherapy has been demonstrated in patients with
      atopic dermatitis, although more double-blind, placebo-controlled studies are
      needed. Based on several studies, it cannot be concluded that mite immunotherapy
      is more dangerous or safer than immunotherapy with grasses, epithelia, or animal
      epithelia. Because the delivery of high doses of allergen carries with it the
      risk for immunoglobulin E (IgE)-mediated events, several methods have been
      developed to reduce specific IgE binding to mite-allergen extracts. An important
      challenge for future mite immunotherapy modalities is the delivery of relatively
      high doses without a significant risk for severe reactions.

PMID- 16899205
TI  - Pollen immunotherapy: selection,prevention, and future directions.
AB  - Pollens are an important cause of allergic rhinitis and asthma. Pollen
      immunotherapy is effective and potentially curative. It has been shown to prevent
      new sensitizations, to prevent the development of asthma in children, and to
      induce long-term benefit. Standardization of allergen extracts is necessary to
      improve immunotherapy safety and efficacy. Knowledge of the local plant taxonomy
      and allergen cross-reactivity is important in selecting clinically relevant
      vaccines. In general, allergenic cross-reactivities correspond to taxonomic
      relations. Tree and weed species demonstrate variable degrees of cross
      reactivity. Most grasses have extensive allergenic cross-reactivity. Mechanism of
      action continues to be an area of investigation, including the induction of
      immunoglobulin G blocking antibodies. Sublingual immunotherapy, concurrent anti
      immunoglobulin E use, hypoallergic peptides, and DNA vaccines are other promising
      technologies.

PMID- 16899208
TI  - Effects of retention intervals on receiver operating characteristics in
      artificial grammar learning.
AB  - Current theories of memory suggest that recognition is composed of separate
      processes of familiarity and recollection (e.g. [Yonelinas, A. P. (2002). The
      nature of recollection and familiarity: a review of 30 years of research. Journal
      of Memory and Language, 46, 441-517]). A key feature of these two processes is
      that they decay, or are forgotten at different rates. The dual-process model has
      also been useful in understanding artificial grammar learning. We obtained
      evidence for recollection and familiarity in artificial grammar learning by
      analyses of receiver operating characteristics (ROC). Furthermore we found that
      these were dissociated by retention intervals of 14 days. The slope of the zROC
      curves deviated reliably from 1 immediately after study and increased towards 1
      suggesting that recollection contributed to recognition decisions but declined
      over the 14-day period leaving familiarity as the only basis for recognition.
      These data show similar patterns to those observed in word-recognition [Gardiner,
      J. M., & Java, R. I. (1991). Forgetting in recognition memory with and without
      recollective experience. Memory &Cognition, 19, 617-623; Tunney, R. J. (submitted
      for publication). Changes in the subjective experience of recognition over time
      suggest independent processes] and confirm the view that recollection and
      familiarity are implicated in artificial grammar learning. Moreover, the data
      confirm the finding that recollection and familiarity-based memory show different
      patterns of forgetting.

PMID- 16899207
TI  - The role of immune tolerance in asthma pathogenesis.
AB  - Immune-mediated tolerance encompasses a wide spectrum of mechanisms that can
      prevent unnecessary and potentially harmful inflammatory responses. An increasing
      number of scientific publications provide proof for the concept that an
      impairment of immune-tolerance mechanisms might be causally related to the
      development of unwanted Th2-driven, allergen-induced airway diseases. In this
      review, we discuss immune tolerance and the evidence supporting its role in
      asthma pathogenesis.

PMID- 16899206
TI  - New approaches to allergen immunotherapy.
AB  - Allergic diseases are common problems affecting 20% to 30% of the US population.
      Mast cells and basophils are the primary effector cells mediating allergic
      inflammation through the triggering of membrane immunoglobulin E receptors
      (FceRI) with antigen. Allergen immunotherapy is used as one treatment for
      allergic disease and results in the inhibition of mast cell and basophil
      responses through unknown mechanisms. In this review, we examine potential
      mechanisms that could result in blunted human mast cell/basophil functional
      responses, strategies aimed at using these mechanisms to develop new
      immunologically based therapies, and recent findings that have broad implications
      toward our understanding of how mast cells/basophils become desensitized.

PMID- 16899209
TI  - Acquisition and transmission of Theileria parva by vector tick, Rhipicephalus
      appendiculatus.
AB  - In order to investigate the transmission dynamics of Theileria parva (T. parva)
      by the brown ear tick, Rhipicephalus appendiculatus (R. appendiculatus), under
      experimental conditions, detection of T. parva in ticks and cattle was performed
      by a quantitative real-time PCR assay. A calf inoculated with a T. parva mixture
      became PCR-positive for T. parva infection on day 8 post-inoculation, and
      subsequently, nymphal ticks were introduced and maintained to feed on the
      infected calf for 6 days. Engorged nymphs were collected daily and allowed to
      molt into adults, and overall, 70.8% (121/171) of the adult ticks acquired the T.
      parva infection. Furthermore, the T. parva infection rate in ticks under field
      conditions was monitored by real-time PCR in R. appendiculatus ticks collected
      from a traditionally managed pastoral land of Zambia, on which Sanga breed cattle
      are traditionally reared and the area has endemic East Coast fever (ECF). A total
      of 70 cattle were randomly selected in the same area and 67 (95.7%) were found to
      be serologically positive for R. appendiculatus tick antigen (RIM36). Twenty-nine
      (43.3%) of the 67 serologically positive cattle were real-time PCR-positive for
      T. parva, although no piroplasms could be detected in the blood smears.
      Unexpectedly, out of 614 R. appendiculatus nymphal and adult ticks collected by
      flagging vegetation, 4.1% were positive for T. parva DNA. However, since the rate
      of transmission of T. parva from infected cattle to ticks and vice versa and the
      serological evidence of exposure to R. appendiculatus ticks in naturally exposed
      cattle were relatively high, it would be wise in such a case to consider vector
      control as well as vaccination against ECF as control measures.

PMID- 16899210
TI  - Dynamically arrested states of matter.
AB  - We outline current developments in our understanding of dynamical arrest, that
      phenomenon in which many particles stop moving in a collective manner. However in
      addition to the question of true dynamical arrest itself, we emphasize the
      development of new tools that can describe relatively sharp changes in the way
      that ergodic systems may be explored. We discuss the concept of new order
      parameters (dynamically available volume), and indicate how they may be applied
      to understand dramatic slowing phenomena present in particle systems, and other
      arenas of soft and complex matter.

PMID- 16899211
TI  - Mass spectrometry in demonstrating the site-specific nitration of hen egg white
      lysozyme by an improved electrochemical method.
AB  - In producing a method for selective protein nitration, we previously demonstrated
      the electrochemical nitration of hen egg white lysozyme to be at Tyr23 initially,
      followed by bisnitration at Tyr20, but with no trisnitration at Tyr53. The
      nitration site was determined by sequencing a tryptic peptide that included Tyr23
      and Tyr20, but possible effects on other regions of the protein were not
      determined. Moreover, the electrooxidation conditions were harsh, involving an
      oxidation potential of +1.2V (vs. saturated calomel electrode [SCE]), no added
      nitrogen source except the lysozyme itself, and long reaction periods with copper
      flag electrodes. Here we report a gentler procedure using much shorter reaction
      times with nitrite as the nitration source, a lower potential (+0.85V vs. SCE),
      and a platinum basket electrode. Intact protein analysis by electrospray Fourier
      transform ion cyclotron resonance mass spectrometry identified mono- and
      bisnitration products with mass increases of +45 and +90 Da, respectively,
      consistent with the substitution of NO(2) for H. In addition, the results
      revealed that no other covalent change in the protein occurred following
      electrooxidation. Nozzle skimmer dissociation of the intact mononitrated species
      localized the modification site to Tyr20 or Tyr23. Matrix-assisted laser
      desorption/ionization time-of-flight and electrospray ionization time-of-flight
      analysis of the tryptic peptides of mononitrated lysozyme identified the site of
      nitration as Tyr23.

PMID- 16899212
TI  - Error propagation in relative real-time reverse transcription polymerase chain
      reaction quantification models: the balance between accuracy and precision.
AB  - Real-time reverse transcription polymerase chain reaction (RT-PCR) has gained
      wide popularity as a sensitive and reliable technique for mRNA quantification.
      The development of new mathematical models for such quantifications has generally
      paid little attention to the aspect of error propagation. In this study we
      evaluate, both theoretically and experimentally, several recent models for
      relative real-time RT-PCR quantification of mRNA with respect to random error
      accumulation. We present error propagation expressions for the most common
      quantification models and discuss the influence of the various components on the
      total random error. Normalization against a calibrator sample to improve
      comparability between different runs is shown to increase the overall random
      error in our system. On the other hand, normalization against multiple reference
      genes, introduced to improve accuracy, does not increase error propagation
      compared to normalization against a single reference gene. Finally, we present
      evidence that sample-specific amplification efficiencies determined from
      individual amplification curves primarily increase the random error of real-time
      RT-PCR quantifications and should be avoided. Our data emphasize that the gain of
      accuracy associated with new quantification models should be validated against
      the corresponding loss of precision.

PMID- 16899213
TI  - Remote treatment of bulimia nervosa and binge eating disorder: a randomized trial
      of Internet-assisted cognitive behavioural therapy.
AB  - The present study investigated the efficacy of self-help based on cognitive
      behaviour therapy in combination with Internet support in the treatment of
      bulimia nervosa and binge eating disorder. After confirming the diagnosis with an
      in-person interview, 73 patients were randomly allocated to treatment or a
      waiting list control group. Treated individuals showed marked improvement after
      12 weeks of self-help compared to the control group on both primary and secondary
      outcome measures. Intent-to-treat analyses revealed that 37% (46% among
      completers) had no binge eating or purging at the end of the treatment and a
      considerable number of patients achieved clinically significant improvement on
      most of the other measures as well. The results were maintained at the 6-month
      follow-up, and provide evidence to support the continued use and development of
      self-help programmes.

PMID- 16899214
TI  - Localization of heparin- and neuropilin-1-recognition sites of viral VEGFs.
AB  - VEGF-A165 plays a central role in neovascularization. The biological activities
      of VEGF-A165 are largely mediated through KDR. VEGF-A165 also binds to cellular
      coreceptors, neuropilin-1 (NP-1), and heparin, via its C-terminal domain,
      resulting in functional modulation. Parapoxvirus-encoded VEGFs (PV-VEGFs), which
      recognize KDR, possess basic amino acid clusters in their C-terminal regions.
      Some PV-VEGFs may interact with NP-1; however, the NP-1- and heparin-binding
      properties have not been fully characterized. Here, we demonstrate that the
      heparin- and NP-1-binding region of PV-VEGFs is located in its C-terminal tail.
      Furthermore, the two arginine residues adjacent to the C-terminus greatly
      contribute to both interactions.

PMID- 16899215
TI  - SALL4 is directly activated by TCF/LEF in the canonical Wnt signaling pathway.
AB  - The SALL4 promoter has not yet been characterized. Animal studies showed that
      SALL4 is downstream of and interacts with TBX5 during limb and heart development,
      but a direct regulation of SALL4 by TBX5 has not been demonstrated. For other SAL
      genes, regulation within the Shh, Wnt, and Fgf pathways has been reported.
      Chicken csal1 expression can be activated by a combination of Fgf4 and Wnt3a or
      Wnt7a. Murine Sall1 enhances, but Xenopus Xsal2 represses, the canonical Wnt
      signaling. Here we describe the cloning and functional analysis of the SALL4
      promoter. Within a minimal promoter region of 31bp, we identified a consensus
      TCF/LEF-binding site. The SALL4 promoter was strongly activated not only by LEF1
      but also by TCF4E. Mutation of the TCF/LEF-binding site resulted in decreased
      promoter activation. Our results demonstrate for the first time the direct
      regulation of a SALL gene by the canonical Wnt signaling pathway.

PMID- 16899217
TI  - Magicin associates with the Src-family kinases and is phosphorylated upon CD3
      stimulation.
AB  - We recently identified a novel actin cytoskeleton-associated protein magicin, for
      merlin and Grb2 interacting cytoskeletal protein. To unravel the cellular
      functions of magicin, we used a yeast two-hybrid system and identified Fyn
      tyrosine kinase as a specific binding partner for magicin. Fyn phosphorylates
      magicin in vitro. In addition to Fyn, Src and Lck also interact with magicin.
      Upon stimulation with anti-CD3 antibody, magicin is phosphorylated in the T
      lymphocyte leukemia Jurkat cell line. Magicin phosphorylation is not observed in
      an Lck-deficient line, J.CaM1.6, indicating that Lck is the major Src family
      kinase for phosphorylating magicin in Jurkat cells. Employing site-directed
      mutagenesis along with in vitro kinase assays, we found that Y64 of magicin is
      phosphorylated by Lck creating a SH2-Grb2 binding motif. Magicin has also been
      identified as a Mediator subunit (MED28) in the nucleus involved in
      transcriptional regulation, therefore we propose that magicin may serve as a
      multi-faceted adaptor/scaffold to relay cellular signaling to the cytoskeleton
      and from the cytoskeleton to the nucleus.

PMID- 16899216
TI  - Dimerization of hSiah proteins regulates their stability.
AB  - HSiah1 and 2 are members of the Ring finger-type family of ubiquitin E3-ligase
      proteins. They contribute to the degradation of multiple targets by interacting
      with both the ubiquitin conjugating enzyme E2 and the substrate to be
      ubiquitylated prior to proteasomal degradation. Ring finger proteins have also
      been shown to regulate their own stability through the proteasomal degradation.
      Here, we report that hSiah2 proteins can form not only homodimers but also
      heterodimers with hSiah1 independently from their Ring finger domain. The
      oligomerization process, in turn, mediates a Ring finger-dependent proteasomal
      degradation of the two proteins. In contrast, such a catalytic activity is not
      observed for hSiah1. Therefore, these results show that the two isoforms exhibit
      differential regulatory properties. Additionally, dimerization provides a
      mechanism to control the steady-state levels of these two enzymes responsible for
      important catalytic activities.

PMID- 16899218
TI  - Overexpression of AGAMOUS-LIKE 28 (AGL28) promotes flowering by upregulating
      expression of floral promoters within the autonomous pathway.
AB  - MADS box genes are known to perform important functions in the development of
      various plant organs. Although the functions of many MADS box genes have
      previously been elucidated, the biological function of the type I MADS box genes
      remains poorly understood. In order to understand the function and regulation of
      the type I MADS box genes, we conducted molecular genetic analyses of AGL28, a
      member of the Malpha class of type I genes. AGL28 was expressed in vegetative
      tissues in a photoperiod-independent manner, but not within the reproductive
      apex. This indicates that AGL28 plays a role in the vegetative phase.
      Overexpression of AGL28 caused precocious flowering via the upregulation of the
      expression of FCA and LUMINIDEPENDENS (LD), both floral promoters within the
      autonomous pathway. However, the loss of AGL28 function did not result in any
      obvious flowering time phenotype, which suggests that AGL28 may perform a
      redundant function. Collectively, our data suggest that AGL28 is a positive
      regulator of known floral promoters within the autonomous pathway in Arabidopsis.

PMID- 16899219
TI  - Regulatory roles of spnT, a novel gene located within transposon TnTIR.
AB  - The transposon TnTIR contains spnIR quorum-sensing system regulating sliding
      motility and the production of nuclease, biosurfactant, and prodigiosin in
      Serratia marcescens. Within TnTIR, a gene named spnT is upstream of and co
      transcribed with spnI. SpnT is a cytoplasmic protein and its level peaks during
      early stationary phase. spnT over-expression resulted in inhibition of sliding
      motility and synthesis of prodigiosin, and biosurfactant similar to spnR. spnT
      but not spnR over-expression induced cell elongation and aberrant DNA replication
      in S. marcescens and Escherichia coli strains. In comparison with wild-type E.
      coli strain, over-expression of spnT in an E. coli priA and dnaC double-mutant
      strain did not lead to the aberrant cell morphology phenotypes, suggesting SpnT
      may act through the recombination-dependent DNA replication system. As spnT over
      expression inhibited swarming but not swimming motility, SpnT may indirectly
      function as a negative regulator of surface-dependent migration and secondary
      metabolite production.

PMID- 16899221
TI  - Structure of full-length bacterial chitinase containing two fibronectin type III
      domains revealed by small angle X-ray scattering.
AB  - Chitinase A1 (ChiA1) from Bacillus circulans WL-12 consists of an N-terminal
      catalytic domain, two fibronectin type III domains (FnIIIDs), and a C-terminal
      chitin-binding domain. The full-length structure of ChiA1 was studied by small
      angle X-ray scattering. The obtained low-resolution structure showed that ChiA1
      is an elongated molecule with a length of approximately 145 A composed of a large
      globular head and a rod-like tail. Combination with known high-resolution
      structures of individual ChiA1 domains provided a model of the domain
      arrangement. In this model, two FnIIIDs connect to each other in an extended rod
      like shape without large bending between the FnIIIDs, and contribute largely to
      the length of ChiA1.

PMID- 16899220
TI  - An open conformation of switch I revealed by Sar1-GDP crystal structure at low
      Mg2+.
AB  - Mg2+ is essential for guanosine triphosphatase activity and plays key roles in
      guanine nucleotide binding and preserving the structural integrity of GTP-binding
      proteins. To understand the structural basis for Mg2+ function during the GDP/GTP
      exchange process, we determined the crystal structure of Delta9-Sar1-GDP at low
      Mg2+ concentration at 1.8A. Two Sar1-GDP molecules in the crystal form a dimer
      with Mg2+ presenting only in molecule B but not in molecule A. The absence of
      Mg2+ induces significant conformational changes in the switch I region in
      molecule A that shows similarities with those of Ha-Ras bound to Sos. The current
      structure reveals an important regulatory role for Mg2+. We suggest that guanine
      nucleotide exchange factor may utilize this feature to generate an open
      conformation for GDP/GTP exchange. Furthermore, we propose a mechanism for COPII
      assembly and disassembly in which dimerization of Sar1 plays an important role.

PMID- 16899222
TI  - The regulation of adiponectin receptors in human prostate cancer cell lines.
AB  - Obesity is a risk factor for prostate cancer, and plasma levels of the adipokine,
      adiponectin, are low in the former but high in the latter. Adiponectin has been
      shown to modulate cell proliferation and apoptosis, suggesting that adiponectin
      and its receptors (Adipo-R1, Adipo-R2) may provide a molecular association
      between obesity and prostate carcinogenesis. We show for the first time, the
      protein distribution of Adipo-R1 and Adipo-R2 in LNCaP and PC3 cells, and in
      human prostate tissue. Using real-time RT-PCR we provide novel data demonstrating
      the differential regulation of Adipo-R1 and Adipo-R2 mRNA expression by
      testosterone, 5-alpha dihydrotestosterone, beta-estradiol, tumour necrosis factor
      alpha, leptin, and adiponectin in LNCaP and PC3 cells. Our findings suggest that
      adiponectin and its receptors may contribute to the molecular association between
      obesity and prostate cancer through a complex interaction with other hormones and
      cytokines that also play important roles in the pathophysiology of obesity and
      prostate cancer.

PMID- 16899223
TI  - Species and tissue differences in the expression of DPPY splicing variants.
AB  - The non-functional dipeptidyl peptidase, DPPY (DPP10), regulates the expression
      and gating of K+ channels in Kv4 family by tightly binding to these pore-forming
      subunits. Neural tissue-specific expression of this and the related DPPX (DPP6)
      is thought to confer rapid inactivation and other unique properties of neuronal
      Kv4 channels. Here we report that DPPY mRNA is abundant in human adrenal gland,
      but very low in the corresponding rat tissue. Furthermore, multiple DPPY splicing
      variants with alternative first exons are significant in the brain, whereas the
      expression of DPPY gene in the adrenal gland and pancreas is predominantly
      initiated at the two latter sites. These splicing variants, as well as an N
      terminal peptide-deleted DPPY, produce similar changes in Kv4.3 gating. Thus,
      transcription of DPPY gene is species- and tissue-specifically controlled.

PMID- 16899225
TI  - A novel computational method to predict transcription factor DNA binding
      preference.
AB  - Transcription factor binds to sequence specific sites in regulatory region to
      control nearby gene's expression. It is termed as the major regulator of
      transcription. However, identifying DNA binding preference of transcription
      factors systematically is still a challenge. By using the nearest neighbor
      algorithm, a novel computational approach was developed to predict transcription
      factor DNA binding preference based on the gene ontology [M. Ashburner, C.A.
      Ball, J.A. Blake, D. Botstein, H. Butler, J.M. Cherry, A.P. Davis, K. Dolinski,
      S.S. Dwight, J.T. Eppig, M.A. Harris, D.P. Hill, L. Issel-Tarver, A. Kasarskis,
      S. Lewis, J.C. Matese, J.E. Richardson, M. Ringwald, G.M. Rubin, G. Sherlock,
      Gene Ontology: tool for the unification of biology, Nat. Genet. 25 (2000) 25-29.]
      and 0/1 encoding system of nucleotide. The overall success rate of Jackknife
      cross-validation test for our predictor reaches 76.6%, which indicates the DNA
      binding preference is closely correlated with its biological functions and
      computational method developed in this contribution could be a powerful tool to
      investigate transcription factor DNA binding preference, especially for those
      novel transcription factors with little prior knowledge on its DNA binding
      preference.

PMID- 16899224
TI  - Overexpression of wild-type PKD2 leads to increased proliferation and invasion of
      BON endocrine cells.
AB  - Carcinoid tumors are rare neuroendocrine tumors with a predilection for the
      gastrointestinal tract. Protein kinase D (PKD), a novel serine/threonine protein
      kinase, has been implicated in the regulation of transport processes in certain
      cell types. We have reported an important role for PKD in stimulated peptide
      secretion from a human (BON) carcinoid cell line; however, the role of PKD
      isoforms, including PKD2, in the proliferation and invasion of carcinoid tumors
      remains unclear. In the present study, we found that overexpression of PKD2 by
      stable transfection of BON cells with PKD2-wild type (PKD2WT) significantly
      increased proliferation and invasion compared to cells transfected with PKD2
      kinase dead (PKD2KD) or pcDNA3 (control). Similarly, inhibition of PKD2 activity
      with small interfering RNA (siRNA) significantly decreased proliferation and
      invasion compared to cells transfected with non-targeting control (NTC) siRNA.
      These data support an important role for PKD2 in carcinoid tumor progression.
      Targeted inhibition of the PKD family may prove to be a novel treatment option
      for patients with carcinoid tumors.

PMID- 16899226
TI  - Controlling gene expression in Drosophila using engineered zinc finger protein
      transcription factors.
AB  - Zinc finger protein transcription factors (ZFP TFs) have been designed to control
      the expression of endogenous genes in a variety of cells. However, thus far the
      use of engineered ZFP TFs in germline transgenic settings has been restricted to
      plants. Here we report that ZFP TFs can regulate gene expression in transgenic
      Drosophila. To demonstrate this, we targeted the promoter of the well
      characterized fushi tarazu (ftz) gene with a ZFP TF activator using the VP16
      activation domain from Herpes simplex virus, and ZFP TF repressors using the
      Drosophila methyl-CpG binding domain (MBD)-like Delta protein. Heat-shock
      inducible expression of the ZFP TF activator and repressors resulted in
      reciprocal effects on ftz regulation, as deduced from changes in the staining
      pattern and intensity of ftz and en gene expression, and from the cuticular
      analysis of first instar larvae. These data demonstrate the utility of ZFP TFs as
      tools for controlling gene expression in the context of a metazoan organism.

PMID- 16899227
TI  - In vivo imaging of tumor growth after electrochemotherapy with cisplatin.
AB  - Imaging methods can give both temporal and spatial dimensions to characterize the
      processes in progression of and/or treatment of specific disease Subcutaneous
      tumors can be cured after electrochemotherapy (ECT). Growth and reduction of
      tumors as a result of cytotoxic therapy can be followed by fluorescence video
      imaging directly on the same animal after treatment. Imaging of tumors should
      bring more information on the cellular effects of ECT. Green fluorescent protein
      (eGFP) expressing B16F10 and LPB tumors implanted in C57Bl/6 mice were treated
      with ECT with cisplatin. The growth or regression of the tumors was monitored
      either classically by using a caliper or by a manual definition of the region of
      interest where critical fluorescence levels were detected on the animals. A very
      good correlation between the two methods was observed. The eGFP mean fluorescence
      emission was only slightly affected by ECT with intravenously injected cisplatin.
      Ex vivo observations under a fluorescence microscope showed that eGFP was only
      detected on the outer layer of the tumor. No fluorescence was detected in the
      central part of the tumors, which were necrotic.

PMID- 16899228
TI  - Modulation of mitochondrial metabolic function by phorbol 12-myristate 13-acetate
      through increased mitochondrial translocation of protein kinase Calpha in C2C12
      myocytes.
AB  - Protein kinase C (PKC) agonists including phorbol 12-myristate 13-acetate (PMA)
      not only induce the redistribution of cytosolic PKC to various subcellular
      compartments but also activate the kinase domain of the protein. In the present
      study we have investigated the nature of mitochondrial PKC pool and its effects
      on mitochondrial function in cells treated with PMA. Treatment of C2C12
      myoblasts, C6 glioma and COS7 cells with PMA resulted in a dramatic
      redistribution of intracellular PKCalpha pool, with large fraction of the protein
      pool sequestered in the mitochondrial compartment. We also observed mitochondrial
      PKCdelta accumulation in a cell restricted manner. The intramitochondrial
      localization was ascertained by using a combination of protection against
      protease treatment of isolated mitochondria and immunofluorescence microscopy.
      PMA-induced mitochondrial localization of PKCalpha was accompanied by increased
      mitochondrial PKC activity, altered cell morphology, disruption of mitochondrial
      membrane potential, decreased complex I and pyruvate dehydrogenase activities,
      and increased mitochondrial ROS production. All of these changes could be
      retarded by treatment with PKC inhibitors. These results show a direct role for
      PMA-mediated PKCalpha translocation to mitochondria in inducing mitochondrial
      toxicity.

PMID- 16899230
TI  - Cardiovascular effects of mixed amphetamine salts extended release in the
      treatment of school-aged children with attention-deficit/hyperactivity disorder.
AB  - BACKGROUND: The cardiovascular safety of mixed amphetamine salts extended release
      (MAS XR) was evaluated in 2968 children 6-12 years of age with attention
      deficit/hyperactivity disorder (ADHD). METHODS: In this prospective, open-label,
      noncomparative, community-based study, subjects whose symptoms of ADHD were well
      controlled with stimulant medication maintained their established treatment
      regimens for 2 weeks before enrollment into the current study. Subjects' regimens
      were then converted to an approximately equivalent once-daily dose of MAS XR 10,
      20, or 30 mg/d according to a medication-conversion algorithm, which could be
      adjusted to 40 mg/d for optimal efficacy and tolerability. Systolic blood
      pressure (SBP), diastolic BP (DBP), and pulse were measured at each study visit.
      Twelve-lead electrocardiography was performed at screening and at the end of the
      extension phase or early termination. RESULTS: No clinically significant changes
      in BP or pulse were observed. Although one subject experienced a QT-prolongation
      interval > 25%, no clinically significant prolongation in the mean QT interval
      was seen. Approximately 2.5% of subjects demonstrated two consecutive SBP or DBP
      values > 95th percentile for age, sex, and height, and 3.6% of subjects' pulse
      increased by > or = 25 to > or = 110 beats per minute. No serious cardiovascular
      adverse events or deaths occurred. CONCLUSIONS: In addition to demonstrated
      efficacy and safety, the cardiovascular profile of MAS XR showed generally small
      divergences from age-specific population norms that pose very limited risk in
      this patient population.

PMID- 16899231
TI  - COMT Association Data in Schizophrenia: New Caveats.

PMID- 16899232
TI  - Cellular co-localization of protein phosphatase 5 and glucocorticoid receptors in
      rat brain.
AB  - Glucocorticoid receptors are widely expressed in brain, where they are thought to
      play a role in controlling neurogenesis and to mediate many of the central
      nervous system effects of stress. In non-neuronal cells, protein phosphatase 5
      (PP5) has been found in complexes with heat shock protein 90 and glucocorticoid
      receptors and may be a negative modulator of glucocorticoid receptor function. In
      the present study, we used co-immunofluorescence analysis to examine whether PP5
      and glucocorticoid receptors are co-expressed at the cellular level in rat brain.
      In several regions containing major populations of glucocorticoid receptor
      expressing neurons, PP5 and glucocorticoid receptors were co-localized at the
      cellular level. These include pyramidal cells of the hippocampal CA1 and CA2
      regions and dentate gyrus granule cells, cerebellar Purkinje neurons, cortical
      pyramidal neurons, neurons of the central nucleus of the amygdala and
      parvocellular neurons of the hypothalamic paraventricular nucleus. There are also
      neuronal populations that are stained strongly for glucocorticoid receptors, such
      as cerebellar granule cells, where PP5 is either absent or below detection
      limits. Likewise, numerous neuronal populations contain PP5, but not
      glucocorticoid receptors. Whereas glucocorticoid receptors are expressed in both
      neurons and glial cells throughout the brain, PP5 appears to be primarily
      expressed in neurons. These studies suggest that glucocorticoid receptors may be
      differentially regulated by phosphatase action in different populations of
      central nervous system cells. Co-localization of PP5 and glucocorticoid receptors
      in brain regions involved in feedback control of the hypothalamus-pituitary
      adrenal axis suggests that PP5 may be an important modulator of glucocorticoid
      receptor responses in this pathway.

PMID- 16899233
TI  - Further evidence that rat liver microsomal glutathione transferase 1 is not a
      cellular protein target for S-nitrosylation.
AB  - By adopting biotin switch method, we recently reported that liver microsomal
      glutathione transferase 1 (MGST1) might not be a protein target for S
      nitrosylation in rat microsomes or in vivo. However, alternative analytic methods
      are needed to confirm this observation, as a single biotin switch method in
      judging specific protein S-nitrosylation in biological samples is increasingly
      recognized as insufficient, or even unreliable. Besides, only MGST1 localized on
      endoplasmic reticulum (ER), but not mitochondria which favors protein S
      nitrosylation was examined in the previous report. Present study was therefore
      carried out to address these issues. Primary cultured hepatocytes were used. A
      physiological existing nitric oxide (NO) donor S-nitrosoglutathione (GSNO) was
      adopted to trigger protein S-nitrosylation. MGST1 was immunoprecipitated and its
      S-nitrosothiol content was measured by the NO probe 2,3-diaminonaphthalene. In
      parallel, S-nitrosylated proteins were immunoprecipitated by a monoclonal anti-S
      nitrosocysteine antibody and probed with an anti-MGST1 antibody. In hepatocytes,
      neither ER nor mitochondria were found to contain S-nitrosylated MGST1 after GSNO
      treatment, showing that differently distributed MGST1 was consistently un
      nitrosylable in the cellular environment. But under broken cell conditions, when
      samples were incubated directly with GSNO, MGST1 S-nitrosylation was indeed
      detectable in both the microsomal and mitochondrial proteins, indicating that
      previous failure in detecting MGST1 S-nitrosylation in microsomes is due to the
      limitations of biotin switch method. These results clearly, if not definitely,
      demonstrate that MGST1 is not a ready candidate for S-nitrosylation in the
      cellular content, despite its susceptibility to S-nitrosylation under broken cell
      conditions.

PMID- 16899234
TI  - Different effects of sulfur amino acids on prolidase and prolinase activity in
      normal and prolidase-deficient human erythrocytes.
AB  - BACKGROUND: Prolidase and prolinase activity is known to be enhanced
      significantly in some diseases. Recently, the effect of amino acids on prolidase
      and prolinase activity in normal and prolidase-deficient human erythrocytes was
      investigated. It was reported that both enzymes were enhanced by glycine and
      alanine in the presence of MnCl(2). METHODS: Erythrocytes were isolated from
      heparinized blood from normal human and a patient with prolidase deficiency.
      Effects of various sulfur amino acids on prolidase and prolinase activities
      against iminodipeptides in the presence of 1 or 0.1 mmol/l MnCl(2) were
      investigated. RESULTS: Prolinase activity against prolylglycine in normal and
      prolidase-deficient erythrocyte lysates was inhibited by L-methionine, NAc-L
      methionine and D,L-methionine in a concentration-dependent manner, but D
      methionine enhanced the activity in low concentrations (0-20 mmol/l). D,L
      Homocysteine inhibited the activity more strongly than other sulfur amino acids
      tested in a concentration-dependent manner. On the other hand, prolidase activity
      against glycylproline was enhanced by L-methionine, D-methionine, D,L-methionine,
      D,L-homocysteine thiolactone and D,L-ethionine. The rates of enhancement by these
      sulfur amino acids were in the following order: D,L-ethionine>D,L-methionine, D
      methionine, D,L-homocysteine thiolactone>L-methionine (10 mmol/l). CONCLUSION:
      The prolinase activity in normal and prolidase-deficient erythrocyte lysates was
      inhibited by L-methionine, D,L-ethionine and D,L-homocysteine. On the other hand,
      prolidase activity in their erythrocyte lysates was enhanced by D,L-ethionine, D
      methionine and L-methionine. These results indicate the effects of these sulfur
      amino acids on prolidase and prolinase activities were different.

PMID- 16899235
TI  - LTA and LPS mediated activation of protein kinases in the regulation of
      inflammatory cytokines expression in macrophages.
AB  - BACKGROUND: Lipoteichoic acid (LTA) and lipopolysaccharide (LPS), the toxicants
      from bacteria, are potent inducers of inflammatory cytokines, such as tumor
      necrosis factor-alpha (TNF) and interleukin-1beta (IL-1). Although LTA is much
      less reported than that on LPS, LTA is regarded as the gram-positive equivalent
      to LPS in some aspects. We investigated the LTA-induced signal transduction and
      biological effects, as well as to compare the effect of LTA with that of LPS.
      METHODS: Kinase assay, ELISA and RT-PCR were performed to delineate LTA and LPS
      signaling as well as to determine the secretion and RNA expression of TNF and IL
      1. RESULTS: Src, Lyn and MAPKs are involved in LTA and LPS signaling in murine
      macrophages. Additionally, blockades of PKC, PI3K and p38, respectively, caused
      significant inhibition of both LTA- and LPS-induced proIL-1/IL-1 and TNF
      expression. ERK inactivation moderately reduced LTA- and LPS-induced proIL-1/IL
      1, but considerably reduced TNF expression. Inhibition of JNK engendered super
      induction of IL-1 secretion, but diminished TNF secretion. Strikingly, both IL-1
      and TNF protein induction were declined by overexpression of dominant negative
      form of JNK. CONCLUSIONS: The results clarify the similarity and difference
      between LTA- and LPS-mediated signal transduction and induction of inflammatory
      cytokines in macrophages.

PMID- 16899236
TI  - Infants' use of category knowledge and object attributes when segregating objects
      at 8.5 months of age.
AB  - The current research investigates infants' perception of a novel object from a
      category that is familiar to young infants: key rings. We ask whether experiences
      obtained outside the lab would allow young infants to parse the visible portions
      of a partly occluded key ring display into one single unit, presumably as a
      result of having categorized it as a key ring. This categorization was marked by
      infants' perception of the keys and ring as a single unit that should move
      together, despite their attribute differences. We showed infants a novel key ring
      display in which the keys and ring moved together as one rigid unit (Move
      together event) or the ring moved but the keys remained stationary throughout the
      event (Move-apart event). Our results showed that 8.5-month-old infants perceived
      the keys and ring as connected despite their attribute differences, and that
      their perception of object unity was eliminated as the distinctive attributes of
      the key ring were removed. When all of the distinctive attributes of the key ring
      were removed, the 8.5-month-old infants perceived the display as two separate
      units, which is how younger infants (7-month-old) perceived the key ring display
      with all its distinctive attributes unaltered. These results suggest that on the
      basis of extensive experience with an object category, infants come to identify
      novel members of that category and expect them to possess the attributes typical
      of that category.

PMID- 16899237
TI  - p57 and Hes1 coordinate cell cycle exit with self-renewal of pancreatic
      progenitors.
AB  - In developing organs, the regulation of cell proliferation and cell cycle exit is
      coordinated. How this coordination is achieved, however, is not clear. We show
      that the cyclin kinase inhibitor p57 regulates cell cycle exit of progenitors
      during the early stages of pancreas formation. In the absence of p57, the number
      of cycling progenitors increases, although expansion of progenitor population is
      prevented by apoptosis. We report that p57 is a direct target of transcriptional
      repression by Notch effector, Hes1. Inactivation of Hes1 results in the
      upregulation of p57 expression in progenitors, leading to cell cycle arrest,
      precocious differentiation and depletion of the progenitor pool. We present
      evidence that in p57/Hes1 double null embryos, the absence of apoptosis results
      in the expansion of the progenitor population. We propose that Hes1 and p57 not
      only coordinate cell cycle exit and self-renewal of pancreatic progenitors during
      an early stage in organogenesis to regulate the number of pancreatic progenitors,
      but could also constitute a surveillance system to eliminate cells with aberrant
      cell cycle characteristics.

PMID- 16899238
TI  - mig-5/Dsh controls cell fate determination and cell migration in C. elegans.
AB  - Cell fate determination and cell migration are two essential events in the
      development of an organism. We identify mig-5, a Dishevelled family member, as a
      gene that regulates several cell fate decisions and cell migrations that are
      important during C. elegans embryonic and larval development. In offspring from
      mig-5 mutants, cell migrations are defective during hypodermal morphogenesis, QL
      neuroblast migration, and the gonad arm migration led by the distal tip cells
      (DTCs). In addition to abnormal migration, DTC fate is affected, resulting in
      either an absent or an extra DTC. The cell fates of the anchor cell in
      hermaphrodites and the linker cells in the male gonad are also defective, often
      resulting in the cells adopting the fates of their sister lineage. Moreover, 2
      degrees vulval precursor cells occasionally adopt the 3 degrees vulval cell fate,
      resulting in a deformed vulva, and the P12 hypodermal precursor often
      differentiates into a second P11 cell. These defects demonstrate that MIG-5 is
      essential in determining proper cell fate and cell migration throughout C.
      elegans development.

PMID- 16899239
TI  - Cordycepin inhibits lipopolysaccharide-induced inflammation by the suppression of
      NF-kappaB through Akt and p38 inhibition in RAW 264.7 macrophage cells.
AB  - Cordyceps militaris, a caterpillar-grown traditional medicinal mushroom, produces
      an important bioactive compound, cordycepin (3'-deoxyadenosine). Cordycepin is
      reported to possess many pharmacological activities including immunological
      stimulating, anti-cancer, anti-virus and anti-infection activities. The molecular
      mechanisms of cordycepin on pharmacological and biochemical actions of
      macrophages in inflammation have not been clearly elucidated yet. In the present
      study, we tested the role of cordycepin on the anti-inflammation cascades in
      lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. In LPS-activated
      macrophage, nitric oxide (NO) production was inhibited by butanol fraction of C.
      militaris and the major component of C. militaris butanol faction was identified
      as cordycepin by high performance liquid chromatography. To investigate the
      mechanism by which cordycepin inhibits NO production and inducible nitric oxide
      synthase (iNOS) expression, we examined the activation of Akt and MAP kinases in
      LPS-activated macrophage. Cordycepin markedly inhibited the phosphorylation of
      Akt and p38 in dose-dependent manners in LPS-activated macrophage. Moreover,
      cordycepin suppressed tumor necrosis factor (TNF-alpha) expression, IkappaB alpha
      phosphorylation, and translocation of nuclear factor-kappaB (NF-kappaB). The
      expressions of cycloxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS)
      were significantly decreased in RAW 264.7 cell by cordycepin. Taken together,
      these results suggest that cordycepin inhibits the production of NO production by
      down-regulation of iNOS and COX-2 gene expression via the suppression of NF
      kappaB activation, Akt and p38 phosphorylation. Thus, cordycepin may provide a
      potential therapeutic approach for inflammation-associated disorders.

PMID- 16899240
TI  - Function of multidrug resistance-associated protein 2 in acute hepatic failure
      rats.
AB  - The function of multidrug resistance-associated protein 2 (Mrp2) in the intestine
      and liver, as well as intestinal Mrp2 expression, was analyzed in CCl(4)-induced
      acute hepatic failure rats with hyperbilirubinemia. The plasma level of bilirubin
      glucuronides, endogenous Mrp2-substrates, was 26 microM at 24 h after CCl(4)
      treatment. Mrp2 protein levels in jejunum decreased to 41% of control level. Mrp2
      mediated efflux of 2,4-dinitrophenyl-S-glutathione (DNP-GSH), an Mrp2-substrate,
      in jejunum decreased to 31% of control in vitro, and was almost completely
      suppressed in vivo to the same level as that in the presence of probenecid, an
      Mrp2-inhibitor. Biliary excretion of DNP-GSH was suppressed to the same level as
      that inhibited by intravenous probenecid. The suppression of Mrp2 and the
      increased plasma bilirubin glucuronides recovered within 24 h thereafter. These
      results suggest that hyperbilirubinemia in disease states may be related to the
      systemic suppression of Mrp2 function.

PMID- 16899241
TI  - Ranbezolid, a novel oxazolidinone antibacterial: in vivo characterisation of
      monoamine oxidase inhibitory potential in conscious rats.
AB  - Ranbezolid, a novel oxazolidinone antibacterial, competitively inhibits monoamine
      oxidase-A (MAO-A), in vitro. The consequences of MAO-A inhibition was evaluated
      in vivo, by testing interaction of Ranbezolid with tyramine (in solution or mixed
      with feed), and amine containing cold remedies on pressor response in conscious
      rats. Single and repeat doses of Ranbezolid (50 mg/kg, p.o.) did not affect
      pressor response to tyramine (5 or 15 mg/kg), but potentiated the same after a
      single dose of 100 mg/kg. Co-administration of Ranbezolid with tyramine in feed
      or with cold remedies also did not potentiate the respective pressor responses.
      These results suggest that Ranbezolid exhibits minimal cardiovascular liability
      associated with MAO-A inhibition.

PMID- 16899242
TI  - Analysis of Mcm2-7 chromatin binding during anaphase and in the transition to
      quiescence in fission yeast.
AB  - Mcm2-7 proteins are generally considered to function as a heterohexameric
      complex, providing helicase activity for the elongation step of DNA replication.
      These proteins are loaded onto replication origins in M-G1 phase in a process
      termed licensing or pre-replicative complex formation. It is likely that Mcm2-7
      proteins are loaded onto chromatin simultaneously as a pre-formed hexamer
      although some studies suggest that subcomplexes are recruited sequentially. To
      analyze this process in fission yeast, we have compared the levels and chromatin
      binding of Mcm2-7 proteins during the fission yeast cell cycle. Mcm subunits are
      present at approximately 1 x 10(4) molecules/cell and are bound with
      approximately equal stoichiometry on chromatin in G1/S phase cells. Using a
      single cell assay, we have correlated the timing of chromatin association of
      individual Mcm subunits with progression through mitosis. This showed that Mcm2,
      4 and 7 associate with chromatin at about the same stage of anaphase, suggesting
      that licensing involves the simultaneous binding of these subunits. We also
      examined Mcm2-7 chromatin association when cells enter a G0-like quiescent state.
      Chromatin binding is lost in this transition in a process that does not require
      DNA replication or the selective degradation of specific subunits.

PMID- 16899243
TI  - Molecular expression and functional involvement of the bovine calcium-activated
      chloride channel 1 (bCLCA1) in apical HCO3- permeability of bovine corneal
      endothelium.
AB  - Corneal endothelium secretes HCO(3)(-) from basolateral (stroma) to apical
      (anterior chamber) compartments. Apical HCO(3)(-) permeability can be enhanced by
      increasing [Ca(2+)](i). We hypothesized that the bovine calcium-activated
      chloride channel 1 (bCLCA1), shown previously by PCR screening to be expressed in
      corneal endothelium, is involved in Ca(2+) activated apical HCO(3)(-)
      permeability. bCLCA1 expression in cultured bovine corneal endothelial cells
      (CBCEC) was examined by in situ hybridization analysis, immunoblotting,
      immunofluorescence and confocal microscopy. Rabbit polyclonal antibodies were
      generated using a 14 aa polypeptide (417-430) from the predicted sequence of
      bCLCA1. The small interference RNA (siRNA) knock down technique was used to
      evaluate the functional involvement of bCLCA1 in apical HCO(3)(-) permeability.
      In situ hybridization confirmed prominent bCLCA1-specific mRNA expression in
      CBCEC. bCLCA1 antiserum detected the heterologously expressed bCLCA1 in HEK293
      cells and a 90kDa band in CBCEC, which was absent when using the pre-immune serum
      or antigen absorption of serum. Immunofluoresence staining with anti-bCLCA1
      antibody and confocal microscopy indicates an apical membrane location in CBCEC.
      In CBCEC transfected with bCLCA1 specific siRNA, bCLCA1 expression was reduced by
      80%, while transfection with siControl scrambled sequence had no effect.
      Increasing [Ca(i)(2+)] by application of ATPgammaS or cyclopiazonic acid (CPA)
      increased apical HCO(3)(-) permeability in siControl transfected CBCEC, while
      having no effect on apical HCO(3)(-) permeability in bCLCA1 specific siRNA
      transfected cells. Baseline HCO(3)(-) permeability, however, was not different
      between controls and siRNA treated cells. We conclude that the calcium-activated
      chloride channel (bCLCA1) is expressed in bovine corneal endothelial cells and
      can contribute to Ca(2+) dependent apical HCO(3)(-) permeability, but not resting
      permeability, across the corneal endothelium.

PMID- 16899244
TI  - Combined integrin activation and intracellular cAMP cause Rho GTPase dependent
      growth cone collapse on laminin-1.
AB  - Cyclic nucleotides regulate the response of both developing and regenerating
      growth cones to a wide range of guidance molecules through poorly understood
      mechanisms. It is not clear how cAMP levels are regulated or how they translate
      into altered growth cone behavior. Here, we show that intracellular cAMP levels
      are influenced by substrata and integrin receptors. We also show that growth
      cones require a substratum-specific balance between cAMP levels, integrin
      function and Rho GTPases to maintain motility and prevent collapse. Embryonic
      chick dorsal root ganglion neurons plated on different concentrations of laminin
      extend growth cones at similar speeds, yet have distinct levels of integrin
      expression, integrin activation and intracellular cAMP levels. Either increasing
      cAMP signaling or activating integrins enhances the rate of growth cone motility,
      but only on substrata where these two factors are endogenously low (i.e. low
      concentrations of laminin). Surprisingly, combining these two positive
      manipulations induces growth cone collapse and retraction on laminin but not on
      fibronectin. Collapse and retraction on laminin are Rho and Rac1 GTPase dependent
      and are associated with internalization of integrins, the primary receptors
      responsible for adhesion. These observations define a novel pathway through which
      cAMP influences growth cone motility and establish a link between integrins, cAMP
      and Rho GTPases in growth cones.

PMID- 16899245
TI  - Early social isolation alters behavioral and physiological responses to an
      endotoxin challenge in piglets.
AB  - Psychosocial stress in the form of maternal deprivation and social isolation
      during early postnatal life induces persistent alterations in behavioral and
      physiological mechanisms of adaptation. One consequence may be an increased
      susceptibility to diseases in later life. Therefore, the aim of the present study
      was to investigate in domestic piglets the effects of a repeated social isolation
      (2 h daily from day 3 to day 11 of age) on behavioral, endocrine and immune
      responses to an endotoxin challenge with lipopolysaccharide (LPS) 1 day or 45
      days after the isolation period. Peripheral LPS administration caused serious
      sickness behavior (somnolence, shivering, vomiting) and provoked profound
      increases in circulating tumor necrosis factor-alpha (TNF-alpha), ACTH and
      cortisol concentrations. The prior social isolation treatment enhanced signs of
      sickness and impaired suckling behavior. Early isolated piglets responded to LPS
      by an increase of shivering on day 12 and by increased vomiting on day 56
      compared to controls. Further, there were considerable delays and reductions of
      time isolated piglets spent suckling on day 12. The repeated isolation stressor
      diminished TNF-alpha increases after LPS, whereas stress hormone levels were not
      significantly affected by isolation treatment. Finally, stronger relationships
      between signs of sickness and physiological measures were revealed in early
      isolated piglets. The duration of somnolence in isolated piglets was related to
      changes of cortisol and TNF-alpha concentrations, and the highest impact on
      duration of shivering was found for changes in cortisol and corticosteroid
      binding globulin levels. The present results suggest a sustained adaptive
      sensitization of coping with infection by social stress experience during early
      development in piglets.

PMID- 16899246
TI  - Lauge-Hansen classification--a literature review.
AB  - The Lauge-Hansen classification of ankle fractures is a historical landmark in
      fracture research. Despite this there are, however, some shortcomings in
      methodology and several papers have demonstrated poor reproducibility. This paper
      reviews Lauge-Hansen's work and the literature evaluating his classification.

PMID- 16899247
TI  - Effect of dissolution temperature on the structures of sodium hyaluronate by flow
      field-flow fractionation/multiangle light scattering.
AB  - Molecular weight distribution (MWD) and structural deformation of ultrahigh
      molecular weight (MW) sodium hylaluronate (10(5)-10(8) g/mol) were studied under
      different sample dissolution temperature conditions, using on-line flow field
      flow fractionation (FlFFF) and multiangle light scattering (MALS). Sodium
      hyaluronate (NaHA) materials from sarcoma fluid have been studied by dissolving
      them in water at three different temperature conditions (5 degrees C, 50 degrees
      C, and 90 degrees C). Frit inlet asymmetrical flow field-flow fractionation (FI
      AFlFFF), with field programming, was utilized for the separation of NaHA by MW,
      and on-line observation of light scattering of fractionated NaHA by MALS was
      performed in order to determine the MWD and molecular conformation. In these
      experiments, NaHA molecules exhibited an extended structure from a formerly
      rather compact geometry when the dissolving temperature was raised to 90 degrees
      C. This study also showed a clear difference in the MWD of NaHA when a
      preliminary filtration process was applied.

PMID- 16899248
TI  - Development of a purge and trap continuous flow system for the stable carbon
      isotope analysis of volatile halogenated organic compounds in water.
AB  - A purge and trap (P&T) continuous flow system was developed in order to
      concentrate high volumes of water for trace analyses and stable carbon isotope
      measurements of volatile halogenated organic compounds (VHOCs) in seawater. The
      P&T parameters were evaluated regarding quality parameters, extraction efficiency
      and isotope fractionation. Precision (about 20%), linearity (>0.9676), and
      recoveries (between 75% and 99%) were reasonable within the large concentration
      range tested. Isotope fractionation was between 1 per thousand and 3 per
      thousand. Finally, the developed system was successfully applied to the
      quantitative and stable carbon isotope analysis of three water samples of
      different origin.

PMID- 16899249
TI  - Collaborative trial validation study of two methods, one based on high
      performance liquid chromatography-tandem mass spectrometry and on gas
      chromatography-mass spectrometry for the determination of acrylamide in bakery
      and potato products.
AB  - A European inter-laboratory study was conducted to validate two analytical
      procedures for the determination of acrylamide in bakery ware (crispbreads,
      biscuits) and potato products (chips), within a concentration range from about 20
      microg/kg to about 9000 microgg/kg. The methods are based on gas chromatography
      mass spectrometry (GC-MS) of the derivatised analyte and on high performance
      liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) of native acrylamide.
      Isotope dilution with isotopically labelled acrylamide was an integral part of
      both methods. The study was evaluated according to internationally accepted
      guidelines. The performance of the HPLC-MS/MS method was found to be superior to
      that of the GC-MS method and to be fit-for-the-purpose.

PMID- 16899250
TI  - Modeling of the moving deformed triple contact line: influence of the fluid
      inertia.
AB  - For partial wetting, motion of the triple liquid-gas-solid contact line is
      influenced by heterogeneities of the solid surface. This influence can be strong
      in the case of inertial (e.g., oscillation) flows where the line can be pinned or
      move intermittently. A model that takes into account both surface defects and
      fluid inertia is proposed. The viscous dissipation in the bulk of the fluid is
      assumed to be negligible as compared to the dissipation in the vicinity of the
      contact line. The equations of motion and the boundary condition at the contact
      line are derived from Hamilton's principle. The rapid capillary rise along a
      vertical inhomogeneous wall is treated as an example.

PMID- 16899251
TI  - Synthesis, characterization and metal adsorption properties of the new ion
      exchanger polymer 3-n-propyl(4-methylpyridinium) silsesquioxane chloride.
AB  - The preparation and anion exchange properties of 3-n-propyl(4-methylpyridinium)
      silsesquioxane chloride polymer are described. This new polymer was prepared by
      the sol-gel processing method and is designated as SiPic+Cl-. It is insoluble in
      water and showed an anion exchange capacity of 1.46x10(-3) mol g-1. The
      adsorption isotherms of ZnCl2, CdCl2 and HgCl2 were determined from aqueous
      solutions and the adsorption equilibria simulations fit the model of fixed
      bidentate centers with the absence of lateral interactions and energetic
      heterogeneity between them. The metal ions diffuse into the solid solution
      interface and are dominantly present as MCl2-(4) species for Zn(II), MCl(2-)4 and
      MCl-3 species for Cd(II) and MCl-3 species for Hg(II).

PMID- 16899252
TI  - Adsorption of cyanuric acid on activated carbon from aqueous solution: effect of
      carbon surface modification and thermodynamic characteristics.
AB  - The performance of a conventional and two surface-modified activated carbon
      samples was investigated for the sorption of cyanuric acid from aqueous solution
      by varying the process parameters such as initial concentration, pH, temperature,
      dose of adsorbents, and agitation time. The modified carbon samples obtained by
      acid and ammonia treatment of the conventional sample had a higher BET surface
      area (989 and 1010 m2 g-1, respectively) and higher specific mesopore surface
      area (27.36 and 33.21 m2 g-1, respectively) compared to the untreated material
      (820 and 18.25 m2 g-1). The solute removal was found to be favored at lower
      solute concentration, increased agitation time, increased adsorbent dose, and
      lower temperature. The modified adsorbents outperformed the conventional
      activated carbon for sorption of cyanuric acid especially at higher pH (>7.5) and
      with increasing temperature. The Freundlich model appears to fit the isotherm
      data better than the Langmuir model. The thermodynamic parameters (DeltaG degrees
      ads, DeltaH degrees, and DeltaS degrees) were evaluated showing that the sorption
      process was thermodynamically favorable, spontaneous, and exothermic. The
      findings can be used for predictive modeling for analysis and design adsorption
      systems for removal of cyanuric acid and other polar atrazine degradation
      products from environmental aqueous samples.

PMID- 16899253
TI  - XPS and XAS studies of copper(II) sorbed onto a synthetic pyrite surface.
AB  - Compounds containing copper are likely candidates to delay iodide migration in
      environmental media through the formation of sparingly soluble phases.
      Preliminary experiments showed that iodide was neither sorbed onto chalcopyrite
      nor by a binary system pyrite/copper(II), although significant amounts of copper
      were present at the pyrite surface. In the present study, spectroscopic studies
      (XPS, XANES and EXAFS) were thus performed to determine the nature of sorbed
      copper species. Although introduced as Cu(II), copper was mainly present at the
      oxidation state (I) on the pyrite surface suggesting a heterogeneous reduction
      process. Moreover, copper appeared tetrahedrally coordinated to two sulfur and
      two oxygen atoms onto the pyrite surface, a chemical environment, which seemingly
      stabilized the metal and made it unreactive towards iodide.

PMID- 16899254
TI  - Use of laterite for the removal of fluoride from contaminated drinking water.
AB  - The effects of different operational variables on the mechanistic function of
      laterite in removal of fluoride have been investigated. Thermodynamic parameters
      such as free energy change, enthalpy, and entropy of the process, as well as the
      sorption isotherm, were evaluated. The extent of solute removal is determined by
      initial solute concentration, operational conditions, laterite dose, and solution
      pH. For a fixed set of experimental conditions, a model equation is developed
      from which the percent removal corresponding to each load of fluoride is
      determined. The mechanism of fluoride adsorption is governed by the zero point
      charge of laterite and follows a first-order rate equation. pH has a vital role
      influencing the surface characteristics of laterite. To simulate the flow
      dynamics, fluoride solution was run through a fixed bed column. The pattern of
      breakthrough curves for different influent fluoride concentration, pH, and column
      bed height was characterized. The column efficiency was tested from the bed depth
      service time model. The elution of the retained fluoride was studied and the
      effectiveness of column operation was determined by the retention-elution cycles.

PMID- 16899255
TI  - Variable dimerization of the Ly49A natural killer cell receptor results in
      differential engagement of its MHC class I ligand.
AB  - Natural killer (NK) cells play a vital role in the detection and elimination of
      virally infected and tumor cells. The Ly49 family of NK receptors regulates NK
      cell function by sensing major histocompatibility complex (MHC) class I molecules
      on target cells. Previous crystal studies revealed that the Ly49A homodimer binds
      one MHC molecule in an asymmetric interaction, whereas the Ly49C homodimer binds
      two MHC in a symmetrical fashion. Moreover, the bound receptors adopt distinctly
      different homodimeric forms: a "closed state" for Ly49A and an "open state" for
      Ly49C. Steric clashes between MHC molecules would preclude the closed Ly49A dimer
      from engaging two MHC in the manner of the open Ly49C dimer. To determine whether
      individual Ly49 receptors can undergo a conformational switch enabling them to
      bind MHC in different ways, we carried out a solution NMR study of unbound Ly49A,
      aided by dipolar coupling technology. This study reveals that, in solution,
      unligated Ly49A adopts a symmetric, open-state, homodimer conformation similar to
      that seen previously for Ly49C. Hence, Ly49A can assume both closed and open
      states. To address whether the Ly49A dimer can bind two MHC molecules in
      solution, besides the binding of one MHC observed in the crystal, we carried out
      analytical ultracentrifugation experiments. Velocity sedimentation demonstrates
      that the Ly49A dimer can engage two MHC molecules in solution, in agreement with
      NMR results showing that unbound Ly49A exists predominantly in the open state.

PMID- 16899256
TI  - Clinical characteristics of Restless legs syndrome in patients with Parkinson's
      disease.
AB  - To assess the characteristics, clinical significance and pathology of Restless
      legs syndrome (RLS) in patients with Parkinson's disease (PD), we studied
      clinical backgrounds, RLS symptoms, polysomnographic (PSG) variables and
      therapeutic outcomes in 13 PD patients with RLS (pRLS), and compared them with
      those of 22 idiopathic RLS patients (iRLS). In all but one pRLS patient, RLS
      symptoms arose within 5 years of PD onset. pRLS patients had a lower prevalence
      of family history of RLS, and the age at onset was higher than in iRLS subjects.
      Scores for the severity scale established by the International Restless Legs
      Syndrome Study Group (IRLS), the Pittsburgh Sleep Quality Index, and the
      suggested immobilization test did not differ between groups. However, the
      periodic limb movements index measured by polysomnogram was smaller in pRLS
      subjects. After RLS treatment, symptoms improved significantly in both groups;
      however, pRLS subjects showed higher IRLS scores despite receiving similar doses
      of RLS medications. The severity of RLS before treatment was quite similar
      between the two groups, but the response to treatment could be poorer in pRLS
      than in iRLS. Thus, degeneration of the diencephalospinal dopaminergic pathway
      due to PD itself and physiological aging could overlap in the pathology of pRLS.

PMID- 16899257
TI  - Surprises in approximating Levenshtein distances.

PMID- 16899259
TI  - Persistent (>24h) long-term depression in the dentate gyrus of freely moving rats
      is not dependent on activation of NMDA receptors, L-type voltage-gated calcium
      channels or protein synthesis.
AB  - Hippocampal long-term depression (LTD) comprises a persistent reduction of
      synaptic strength that is typically induced by low frequency stimulation (LFS).
      Although LTD has been described for the dentate gyrus in vitro, this phenomenon
      in the dentate gyrus of the intact animal is less well understood. In the current
      study, we investigated the contribution of NMDA receptors, L-type voltage gated
      calcium channels and protein synthesis to LFS-induced LTD in the dentate gyrus of
      freely moving rats. Animals were implanted with electrodes to enable chronic
      measurement of evoked potentials from medial perforant path-dentate gyrus
      synapses. LTD persisted for at least 24h, and was unaffected by prior treatment
      with the NMDA receptor antagonists AP5 or ifenprodil, which, in contrast,
      prevented LTP. Neither the L-type voltage-gated calcium channel antagonist,
      methoxyverapamil, nor the protein translation inhibitors, anisomycin or emetine
      had an effect on the profile of LTD. Our results suggest that NMDA receptors and
      L-type voltage-gated calcium channels are not involved in the induction of LTD in
      the dentate gyrus in vivo. Intriguingly, persistent LTD can be established
      without the synthesis of new proteins, suggesting that in the dentate gyrus,
      alternative mechanisms exist for the sustainment of enduring LTD.

PMID- 16899258
TI  - Activation of NR2B-containing NMDA receptors is not required for NMDA receptor
      dependent long-term depression.
AB  - The triggering of both NMDA receptor-dependent long-term potentiation (LTP) and
      long-term depression (LTD) in the CA1 region of the hippocampus requires a rise
      in postsynaptic calcium. A prominent hypothesis has been that the detailed
      properties of this postsynaptic calcium signal dictate whether LTP or LTD is
      generated by a given pattern of synaptic activity. Recently, however, evidence
      has been presented that the subunit composition of the NMDA receptor (NMDAR)
      determines whether a synapse undergoes LTP or LTD with NR2A-containing NMDARs
      triggering LTP and NR2B-containing NMDARs triggering LTD. In the present study,
      the role of NR2B-containing synaptic NMDARs in the induction of LTD in CA1
      pyramidal cells has been studied using the selective NR2B antagonists, ifenprodil
      and Ro25-6981. While both antagonists reduced NMDAR-mediated synaptic currents,
      neither prevented induction of LTD. These results demonstrate that activation of
      NR2B-containing NMDARs is not an absolute requirement for the induction of LTD in
      the hippocampus.

PMID- 16899261
TI  - Sleep-wake study in an animal model of acute and chronic heat stress.
AB  - The study of the variations in different parameters of sleep-wake states
      following exposure to high environmental heat in three different age groups of
      freely moving rats have been presented in this paper. Each age group of rats was
      subdivided in three group (i) acute heat stress--subjected to a single exposure
      for 4 h in the BOD (Biological Oxygen Demand) incubator at 38 degrees C; (ii)
      chronic heat stress--exposed for 21 days daily for 1 h in the incubator at 38
      degrees C, and (iii) handling control groups. The polygraphic, analog as well as
      digital sleep-wake recordings were performed just after the heat exposure from
      acute stressed rats and on 22nd day from chronic stressed rats. The results of
      this study revealed that acute exposure to high environmental heat increases
      sleep efficiency with significant increase in SWS (slow wave sleep) decrease in
      AWA (awake) time in all three age groups of rats. The increase in SWS and the
      sleep efficiency in these groups of rats at the cost of decreased time of AWA,
      indicates the involvement of the hypothalamus in thermoregulatory mechanism to
      conserve the energy of the body following sudden exposure to high heat. However,
      the reverse results were observed in the chronic stressed groups of rats, which
      have occurred mostly owing to the adaptations of the brain functions due to
      repetitive exposure to environmental heat. In consequence, the present study
      exhibits that the sleep is highly susceptible to the environmental heat and it is
      sensitive to the intensity, duration and the mode of exposure.

PMID- 16899260
TI  - Effect of chronic restraint stress on carbohydrate metabolism in rat.
AB  - There is some evidence suggesting that stress may induce diabetes mellitus; the
      effects of restraint stress however need to be investigated. The present study
      investigates the role of chronic restraint stress on carbohydrate metabolism in
      male rats. The animals of the stressed group (n=8) were exposed to different
      restraint stressors (1 h twice daily) for 30 days. On days 1, 15 and 30, before
      stress exposure, the animals were weighed and fasting blood samples were obtained
      by tail snipping and subsequently oral glucose tolerance tests (OGTT) were
      carried out. Fasting plasma glucose levels on the 15th day and the plasma glucose
      concentrations, on the 15th and 30th days of the experiment at 15 and 60 min
      following OGTT, in the stressed group, were significantly higher as compared to
      the control group. In the stressed group, fasting plasma insulin levels on the
      15th and 30th days of the experiment and the plasma insulin concentrations, on
      the 15th day at 15 and 60 min after performing OGTT, were significantly lower as
      compared to the control group. Fasting plasma corticosterone concentrations were
      significantly increased on the 15th day of the experiment in the stressed rats as
      compared to the control rats and to concentrations on the 1st day. The weights of
      the stressed rats on the 15th and 30th experimental days were significantly lower
      than the controls. In conclusion, chronic restraint stress for 30 days leads to
      low body weight gain in rats and impairs glucose metabolism perhaps by affecting
      corticosterone and insulin secretion and by inducing a degree of insulin
      resistance.

PMID- 16899262
TI  - Metabolic sensing neurons and the control of energy homeostasis.
AB  - The brain and periphery carry on a constant conversation; the periphery informs
      the brain about its metabolic needs and the brain provides for these needs
      through its control of somatomotor, autonomic and neurohumoral pathways involved
      in energy intake, expenditure and storage. Metabolic sensing neurons are the
      integrators of a variety of metabolic, humoral and neural inputs from the
      periphery. Such neurons, originally called "glucosensing", also respond to fatty
      acids, hormones and metabolites from the periphery. They are integrated within
      neural pathways involved in the regulation of energy homeostasis. Unlike most
      neurons, they utilize glucose and other metabolites as signaling molecules to
      regulate their membrane potential and firing rate. For glucosensing neurons,
      glucokinase acts as the rate-limiting step in glucosensing while the pathways
      that mediate responses to metabolites like lactate, ketone bodies and fatty acids
      are less well characterized. Many metabolic sensing neurons also respond to
      insulin and leptin and other peripheral hormones and receive neural inputs from
      peripheral organs. Each set of afferent signals arrives with different temporal
      profiles and by different routes and these inputs are summated at the level of
      the membrane potential to produce a given neural firing pattern. In some obese
      individuals, the relative sensitivity of metabolic sensing neurons to various
      peripheral inputs is genetically reduced. This may provide one mechanism
      underlying their propensity to become obese when exposed to diets high in fat and
      caloric density. Thus, metabolic sensing neurons may provide a potential
      therapeutic target for the treatment of obesity.

PMID- 16899263
TI  - Pup circadian rhythm entrainment--effect of maternal ganglionectomy or
      pinealectomy.
AB  - In rodents, during late embryonic and early neonatal development, circadian
      rhythms develop in synchrony with those of their mothers, which in turn are
      synchronized with the environmental photoperiod. This paper examines the effect
      of maternal ganglionectomy (pineal gland sympathetic denervation) or extirpation
      of the pineal gland on pups' drinking rhythms, a behavior that is continuously
      monitored in individual animals starting after weaning and studied up to 3 weeks
      later. Maternal ganglionectomy or pinealectomy performed on the 7th day of
      gestation significantly disrupts rat pups' drinking behavior, within and among
      litters. In both treatments, circadian rhythm characteristics of the free-running
      period (tau), phase, amplitude and alpha were significantly altered compared to
      those of the control pups born from sham-operated mothers. With the exception of
      the alpha component, both maternal treatments have similar effects. When
      melatonin was given to the mothers instead of the endogenous pineal secretory
      activity for 5 days during the late period of gestation, this treatment reversed
      the effects of maternal ganglionectomy and pinealectomy. These observations,
      together with previous studies of our group, indicate that the maternal superior
      cervical ganglia and pineal gland are necessary components of the mechanism for
      maternal synchronization, and that maternal melatonin may, directly or
      indirectly, affect the performance of the pups' central oscillator during early
      pup rat development.

PMID- 16899264
TI  - Homoisoflavanones from Disporopsis aspera.
AB  - From cytotoxic extracts of the roots of Disporopsis aspera Engl. (Liliaceae) a
      homoisoflavanone, disporopsin (3-(2',4'-dihydroxy-benzyl)-5,7-dihydroxy-chroman-4
      one) (1) and three rare methyl-homoisoflavanones, 3-(4'-hydroxy-benzyl)-5,7
      dihydroxy-6-methyl-chroman-4-one (2), 3-(4'-hydroxy-benzyl)-5,7-dihydroxy-6,8
      dimethyl-chroman-4-one (3) and 3-(4'-hydroxy-benzyl)-5,7-dihydroxy-6-methyl-8
      methoxy-chroman-4- one (4) along with five other known compounds, N-trans
      feruloyl tyramine (5), adenine (6), 5-(hydroxymethyl)-2-furfural (7), beta
      sitosterol (8) and beta-sitosteryl glucopyranoside (9) were isolated. The
      structures of compounds 1-2 were elucidated by spectral data (1, 2-D NMR and
      EIMS). The four homoisoflavanones (1-4) were found to be cytotoxic against a
      series of human cancer cell lines (HCT15, T24S, MCF7, Bowes, A549 and K562) with
      IC(50) ranging from 15 to 200 microM. Possible biosynthesis routes for
      homoisoflavonoids (1-4) are discussed.

PMID- 16899265
TI  - Digestive properties of the venom of the Australian Coastal Taipan, Oxyuranus
      scutellatus (Peters, 1867).
AB  - The digestive properties of Australian elapid snake venoms have not been studied
      to any great extent. To address this, the in vitro digestive properties of
      Oxyuranus scutellatus (Australian Coastal Taipan) venom were investigated in a
      simulation of the in vivo conditions using the parameters reported for the
      stomach of snakes and representative prey for this species. The amount of soluble
      protein released was measured over time using a bicinchoninic acid (BCA) assay.
      Dismembered mouse hindlegs were injected intramuscularly with 0.1 ml O.
      scutellatus venom (concentration 10 mg/ml) and maintained in a micro-anaerobic,
      acidic environment (pH approximately 1.2-1.7) at 25 degrees C. The bathing liquid
      was sampled every 24 h for 7 days, and assayed for soluble protein. Statistical
      analysis revealed that O. scutellatus venom increased the rate at which proteins
      were released when compared to a negative control suggesting the potential
      importance of envenomation in the digestion of whole prey.

PMID- 16899266
TI  - Anticoagulant effect of Naja naja venom 5'nucleotidase: demonstration through the
      use of novel specific inhibitor, vanillic acid.
AB  - The snake venom proteins affect hemostasis by either advancing/delaying blood
      coagulation. Apart from proteases and phospholipase A(2)s (PLA(2)s),
      5'nucleotidase is known to affect hemostasis by inhibiting platelet aggregation.
      In this study, the possible involvement of Naja naja venom 5'nucleotidase in
      mediating anticoagulant affect is evaluated. Vanillic acid selectively and
      specifically inhibited 5'nucleotidase activity among other enzymes present in N.
      naja venom. It is a competitive inhibitor as evident of inhibition relieving upon
      increased substrate concentration. Vanillic acid dose dependently inhibited the
      anticoagulant effect of N. naja venom up to 40%. This partial involvement of
      5'nucleotidase in mediating anticoagulant effect is substantiated by concanavalin
      A (Con-A) inhibition studies. Con-A, competitively inhibited in vitro protease
      and 5'nucleotidase activity up to 100%. However, it did not exhibit inhibitory
      activity on PLA(2). The complete inhibition of anticoagulant effect by Con-A upon
      recalcification time suggests the participation of both 5'nucleotidase and
      protease in mediating anticoagulant effect of N. naja venom. Vanillic acid and
      Con-A inhibition studies together suggest that probably 5'nucleotidase interacts
      with one or more factors of intrinsic pathway of blood coagulation to bring about
      anticoagulant effect. Thus, this study for the first time demonstrates the
      involvement of 5'nucleotidase in mediating N. naja venom anticoagulant effect.

PMID- 16899267
TI  - Purification and characterization of Ophiophagus hannah cytotoxin-like proteins.
AB  - Three cytotoxin-like proteins from the venom of Ophiophagus hannah were isolated
      by a combination of ion exchange chromatography and reverse phase HPLC. Amino
      acid sequence analysis revealed that these proteins all consisted of 63 amino
      acids and shared approximate 50% and 56% sequence identity with Naja naja atra
      cardiotoxins and cardiotoxin-like basic proteins (CLBPs), respectively. CD
      spectra revealed that their secondary structure was dominated with beta-sheet as
      those noted with cardiotoxins and CLBPs. O. hannah cytotoxin-like protein
      exhibited a cell-lytic activity on SK-N-SH cells, but its activity was more weak
      than that noted for N. naja atra cardiotoxin 3. Alternatively, apoptotic cell
      death was induced by the addition of N. naja atra CLBP. Based on the sequence
      information with the toxin molecules, the functional residues and regions related
      to the differential activity with O. hannah cytotoxin-like protein, cardiotoxin
      and CLBP are discussed.

PMID- 16899268
TI  - Bulk-wave and guided-wave photoacoustic evaluation of the mechanical properties
      of aluminum/silicon nitride double-layer thin films.
AB  - The development of devices made of micro- and nano-structured thin film materials
      has resulted in the need for advanced measurement techniques to characterize
      their mechanical properties. Photoacoustic techniques, which use pulsed laser
      irradiation to nondestructively induce very high frequency ultrasound in a test
      object via rapid thermal expansion, are suitable for nondestructive and non
      contact evaluation of thin films. In this paper, we compare two photoacoustic
      techniques to characterize the mechanical parameters of edge-supported aluminum
      and silicon nitride double-layer thin films. The elastic properties and residual
      stresses in such films affect their mechanical performance. In a first set of
      experiments, a femtosecond transient pump-probe technique is used to investigate
      the Young's moduli of the aluminum and silicon nitride layers by launching ultra
      high frequency bulk acoustic waves in the films. The measured transient signals
      are compared with simulated transient thermoelastic signals in multi-layer
      structures, and the elastic moduli are determined. Independent pump-probe tests
      on silicon substrate-supported region and unsupported region are in good
      agreement. In a second set of experiments, dispersion curves of the A(0) mode of
      the Lamb waves that propagate along the unsupported films are measured using a
      broadband photoacoustic guided-wave method. The residual stresses and flexural
      rigidities for the same set of double-layer membranes are determined from these
      dispersion curves. Comparisons of the results obtained by the two photoacoustic
      techniques are made and discussed.

PMID- 16899269
TI  - Suprabasal overexpression of beta-1 integrin is induced by bovine papillomavirus
      type 1.
AB  - In a normal stratified squamous epithelium, beta1-integrin is expressed in basal
      epithelial cells. In BPV-induced fibropapillomas beta1-integrin is overexpressed
      and aberrantly localized, with uniform expression in the lower spinous layer, and
      sporadic expression within the mid-spinous region that co-localizes with
      expression of the viral E5 and E7 oncoproteins. In situ hybridization of
      fibropapillomas for beta1-integrin RNA revealed sporadic hybridization in the
      spinous layer, indicating transcriptional induction. Beta1-integrin expression in
      cultured keratinocytes requires exogenous EGF in the media, but this requirement
      is lost if E7 is expressed, and E7 was able to abrogate the EGF-requirement of
      normal keratinocytes for the activation of ERK and DNA synthesis. Within
      fibropapillomas, suprabasal expression of E5 and E7 correlated with suprabasal
      expression of beta1-integrin and PCNA, indicating that vegetative viral
      replication in the spinous layer correlated with the expression of E7 and beta1
      integrin. The ability of BPV-1 E7 to support beta1-integrin expression and EGF
      independent DNA synthesis and the activation of ERK are the first biochemical
      correlates of its expression in keratinocytes.

PMID- 16899270
TI  - Distance impairs postural stability only under binocular viewing.
AB  - Prior studies indicate that postural stability under binocular viewing is not
      better than under monocular viewing. This was tested at the distances of 145 cm
      [Fox, C.R. (1990). Some visual influences on human postural equilibrium:
      binocular versus monocular fixation. Perception and Psychophysics, 47 (5), 409
      422] and 90 cm [Isotalo, E., Kapoula, Z., Feret, P.H., Gauchon, K., Zamfirescu,
      F., & Gagey, P.M. (2004). Monocular versus binocular vision in postural control.
      Auris Nasus Larynx, 31 (1), 11-17]. On the other hand, postural stability is
      known to decrease with distance increase. We re-examined the effect of binocular
      versus monocular viewing on postural stability at near and far distances (40 and
      200 cm), and for both young (25.7+/-2.7 years), and old subjects (61.2+/-4.6
      years). For both groups of subjects, proximity decreased the area of CoP, the
      standard deviation of antero-posterior sway (SDy) and the variance of speed. The
      group of elderly presented increased variance of speed at far distance in
      comparison with young subjects. The novel finding is the interaction between
      distance and viewing condition. Under binocular viewing, the area of CoP was
      significantly higher at far distance than at near; in contrast, monocular viewing
      produced similar CoP values at both distances. Increased instability at far
      distance when both eyes are viewing is attributed to decreased sensitivity to
      binocular disparity cues and to visual motion in depth resulting from body sway.
      Monocular viewing would provide similar stability at far and at near distance,
      because sensitivity to lateral visual motion, detected monocularly, decreases
      less with distance than sensitivity to binocularly detected motion in depth.
      Alternatively, such monocular viewing could increase subject's attention and lead
      to tighter postural control regardless of the distance.

PMID- 16899271
TI  - Fate and effect of quaternary ammonium compounds on a mixed methanogenic culture.
AB  - The potential inhibitory effect of four quaternary ammonium compounds (QACs) and
      Vigilquat, a commercial sanitizer which is a mixture of the four QACs, was
      investigated at concentrations up to 100 mg/L using a mixed, mesophilic (35
      degrees C) methanogenic culture. Dextrin and peptone were used as the carbon and
      energy sources. A batch assay conducted at a range of QAC concentrations showed
      that QACs were inhibitory to methanogens at and above 25 mg/L. Methanogenesis was
      more susceptible to QAC inhibition than acidogenesis. Adsorption of QACs on
      biomass was successfully simulated with the Freundlich isotherm equation. The
      inhibitory effect of Vigilquat on the mixed methanogenic culture was also
      investigated in a batch reactor fed with dextrin and peptone. Methanogens were
      inhibited when the total QAC concentration reached 30 mg/L and volatile fatty
      acids (VFAs) accumulated. However, methane production recovered in 57 days of
      incubation, and all VFAs were consumed, suggesting that a prolonged incubation
      period is necessary for the methanogens to overcome the transient inhibition at a
      relatively low QAC concentration. None of the QACs tested in this study was
      biodegraded under methanogenic conditions.

PMID- 16899272
TI  - Bacteria removal in septic effluent: influence of biofilm and protozoa.
AB  - Numerous biological, physical and chemical parameters are involved in the
      retention and removal of bacteria in wastewater treatment systems. Biological
      parameters, such as biofilms and protozoa grazing activity, are often mentioned
      but few studies provide a better understanding of their influence. In this study,
      the effect of bacterivorous protozoa on pathogenic indicator bacteria removal was
      investigated in septic effluent and in the presence of a biofilm coating glass
      slides. Endogenous bacteria from septic effluent were quantified. First, bacteria
      removal was compared between septic effluents treated or not with an inhibitor of
      protozoa (cycloheximide). The mortality rates were 10 times lower in treated
      effluent (96 CFU mL(-1) d(-1)) than in untreated effluent (1100 CFU mL(-1) d(
      1)). Secondly, the efficiency of bacteria removal was studied (i) with a biofilm
      surface and active protozoa, (ii) with a biofilm surface and inactivated
      protozoa, (iii) with a clean surface. Protozoa in the presence of a biofilm were
      responsible for 60% of bacteria removal. Biofilm without protozoa and a clean
      surface each removed similar quantities of bacteria. Grazing by protozoa could be
      an important biological mechanism for bacterial elimination in wastewater
      treatment systems.

PMID- 16899273
TI  - Fate of arsenic compounds in poultry litter upon land application.
AB  - The use of the organic As compound, roxarsone, as an antibiotic additive to
      poultry feed continues to raise concern over potential negative environmental
      impacts. Total As concentration in poultry litter can reach >40 mg kg(-1) and
      both roxarsone and its mineralization product As(V) have been identified in
      poultry litters (PL). To investigate the fate of these As species upon land
      application of PL we conducted two studies. In the first, an Orangeburg soil
      (Ultisol from the Atlantic Coastal Plain) was spiked with either 20 mg kg(-1)
      As(V) or roxarsone and incubated at 10% moisture content for 4 months.
      Exchangeable As was determined periodically by extraction with 0.1M PO(4). Both
      As(V) and roxarsone displayed similar desorption; initially, approximately 70% of
      added As was ligand exchangeable and this decreased to 35% after 4 months
      incubation, presumably due to either slow sorption reactions or a change in solid
      phase speciation of As to less exchangeable forms. In the second study, various
      manipulations of two PL samples were applied to the Orangeburg soil at realistic
      field application rates. The treatments were wet to 10% moisture content and
      water soluble As, Cu and organic carbon (DOC) was measured over 30 days. Arsenic
      and Cu solubility were highest from the dried litter samples. Ashing of the PLs
      decreased soluble As and Cu, presumably because of the loss of organic matter
      from the ashed litter and subsequent decrease in DOC. Application of leachates
      from either PL resulted in higher concentrations of soluble As and Cu than when
      the soil was amended with equivalent concentrations of soluble As and Cu
      dissolved in DI H(2)O. We hypothesize that the increased levels of DOC from the
      PL treatments enhance As and Cu solubility through competitive sorption and
      complexation, respectively. In fact, As and Cu solubility was correlated to DOC
      levels in the amended soil extracts. Even though land application of PL
      introduced relatively low concentrations of As and Cu to soil it appeared that
      other soluble constituents of PL significantly enhanced As and Cu solubility.

PMID- 16899275
TI  - Sulphate toxicity to the aquatic moss, Fontinalis antipyretica.
AB  - The aquatic moss, Fontinalis antipyretica was exposed to elevated sulphate
      concentrations for 21-days. Gametophores were sectioned to 2 cm lengths and
      exposed to sulphate concentrations up to 1500 mg/l, in waters of different water
      hardness. Significant reductions in shoot length, dry weight, and chlorophyll a
      and b concentrations (per gram dry weight) were observed in soft water (19 mg/l
      as CaCO3); however, effects were significantly reduced in waters of increasing
      hardness (up to 105 mg/l as CaCO3). The substantial reduction of sulphate
      toxicity in waters of increasing hardness suggests water chemistry plays a
      significant role in affecting sulphate toxicity and should be considered when
      setting sulphate discharge limits.

PMID- 16899274
TI  - Iron-mediated reduction rates and pathways of halogenated methanes with nanoscale
      Pd/Fe: analysis of linear free energy relationship.
AB  - The influence of halogen substitution in chlorinated methanes and brominated
      methanes on their abiotic reductive dehalogenation with nanoscale Pd/Fe
      bimetallic particles was investigated in this study. The 0.2% and 1.0% Pd/Fe
      particles, with particle sizes of less than 100nm, were synthesized in the
      laboratory. Reduction of the halogenated methanes with the Pd/Fe particles
      followed pseudo-first-order kinetics. The Pd/Fe bimetallic particles demonstrated
      at least an order of magnitude higher in reactivity compared to the unpalladized
      Fe particles of similar particle size. Comparing the 0.2% Pd/Fe and the 1.0%
      Pd/Fe particles, the latter exhibited higher reduction rates of various
      halogenated methanes. On the other hand, the reduction rates of chlorinated
      methanes were consistently lower than those of their brominated counterparts. The
      compounds with higher number of halogen substitutions were more readily reduced
      than the lightly halogenated ones. Coupled hydrogenolysis-elimination processes
      were the important mechanism for complete dehalogenation of the chlorinated and
      brominated methanes. From the kinetic examination of their transformation rates
      and mechanistic insight into the associated pathways, an attempt to analyze
      linear free energy relationship between the observed kinetics and the associated
      thermodynamic constants was performed. The observed reaction rate constants were
      analyzed for their correlations with one-electron potential (E(1)), two-electron
      potential (E(2)), bond dissociation energy (BDE) and the lowest unoccupied
      molecular orbital (LUMO) energy (E(LUMO)). LUMO energy appeared to be the best
      descriptor for the kinetic prediction, while E(1) and E(2) might be more suitable
      for mechanistic analysis.

PMID- 16899276
TI  - Life histories and the evolution of aging in bacteria and other single-celled
      organisms.
AB  - The disposable soma theory of aging was developed to explore how differences in
      lifespans and aging rates could be linked to life history trade-offs. Although
      generally applied for multicellular organisms, it is also useful for exploring
      life history strategies of single-celled organisms such as bacteria. Motivated by
      recent research of aging in E. coli, we explore the effects of aging on the
      fitness of simple single-celled organisms. Starting from the Euler-Lotka
      equation, we propose a mathematical model to explore how a finite reproductive
      lifespan affects fitness and resource allocation in simple organisms. This model
      provides quantitative predictions that have the potential for direct comparison
      with experiment, providing an opportunity to test the disposable soma theory more
      directly.

PMID- 16899277
TI  - A preliminary study on the occurrence and behavior of sulfonamides, ofloxacin and
      chloramphenicol antimicrobials in wastewaters of two sewage treatment plants in
      Guangzhou, China.
AB  - Wastewater samples collected from two sewage treatment plants (STPs) in
      Guangzhou, China were acidified, solid-phase extracted (SPE) with Oasis HLB
      cartridges, followed by instrumental measurement by high performance liquid
      chromatography (HPLC) coupled with a diode array UV detector (DAD) and a
      fluorescence detector (FLD) for the occurrence and fate of antimicrobial
      compounds sulfadiazine (SDZ), sulfamethoxazole (SMX), ofloxacin (OFX) and
      chloramphenicol (CAP). Antimicrobials have been detected at 5.10-5.15, 5.45-7.91,
      3.52-5.56 and 1.73-2.43 microg L(-1) for SDZ, SMX, OFX and CAP in the raw sewages
      of the two STPs, respectively. The concentrations of antimicrobials do not show
      substantial changes after preliminary mechanical sedimentation. No quantifiable
      sulfonamides and chloramphenicol have been identified, and >85% of ofloxacin has
      been removed in the effluents after activated sludge treatment in the two STPs,
      indicating that activated sludge treatment is effective and necessary to remove
      antimicrobial substances in municipal sewage.

PMID- 16899278
TI  - Spatial and temporal trends of volatile organic compounds (VOC) in a rural area
      of northern Spain.
AB  - Ambient concentrations of volatile organic compounds (VOCs) were measured at 40
      rural sampling points in Navarre (northern Spain). Air samples were collected by
      means of sorbent passive sampling and analyzed by thermal desorption (TD) and gas
      chromatography/mass-selective detector (GC/MSD). A total of 140 VOCs were
      identified during the study, which was carried out between May to October 2004
      for a total of a 10 biweekly sampling campaigns. Concentrations of benzene,
      toluene, ethylbenzene, m/p-xylenes, o-xylene (BTEX) and 1,3,5-trimethylbenzene
      were determined in order to investigate their temporal and spatial distributions.
      Geostatistical analysis pointed to traffic as the main emission source of these
      compounds. Supporting this idea, BTEX and nitrogen oxides concentrations were
      found to be highly significantly correlated (r = 0.495, P = 0.001), whereas a
      strong negative correlation between BTEX and ozone was also observed (r = -0.355,
      P = 0.025). The concentrations for the BTEX group were similar to the values that
      have been previously reported for other rural areas.

PMID- 16899279
TI  - Influence of atmospheric pollutants on agriculture in developing countries: a
      case study with three new wheat varieties in Pakistan.
AB  - The performance of three wheat varieties (Inqilab-91, Punjab-96, Pasban-90) was
      investigated in open-top chambers with charcoal-filtered air (FA), unfiltered air
      (UFA) and unchambered field plots (AA) during the 2003-2004 season at a semi
      urban site in Lahore, Pakistan. The 8-h daily mean O(3), NO(2) and SO(2)
      concentrations in UFA and AA remained 72, 28 and 15 ppb, respectively. Plants
      grown in UFA and AA showed stunted growth and accelerated rate of leaf senescence
      with pronounced reductions in stomatal conductance (7-24%), net photosynthetic
      rate (20-22%) and photosynthetic efficiency (9-17%) compared with FA plants. A
      mid-season harvest of 10-week-old plants revealed reduced plant fresh (14-37%)
      and dry weights (15-43) in UFA compared to FA counterparts. Grain yield recorded
      after a full season of growth was drastically reduced in UFA with 43% for Pasban
      90, 39% for Punjab-91 and 18% for Inqilab-91 compared with FA control plants.
      Nutritional quality of seeds was also significantly reduced in UFA and AA with
      respect to starch, but not in protein and vitamin-E contents when compared with
      FA plants. This investigation carried out in a major developing country of
      southeast Asia has shown alarming effects of atmospheric pollutants on both yield
      and nutritional quality of an important cereal crop that needs urgent attention
      to maintain the agricultural systems with parallel efforts to reduce the
      emissions in the region.

PMID- 16899280
TI  - Relationship between climate, pollen concentrations of Ambrosia and medical
      consultations for allergic rhinitis in Montreal, 1994-2002.
AB  - The aim of this study is to evaluate the influence of meteorological factors on
      Ambrosia pollen concentrations and its impact on medical consultations for
      allergic rhinitis of residents from various socio-economic levels in Montreal
      (Quebec, Canada) between 1994 and 2002. The study was conducted to recognize the
      sensitivity of pollen productivity to daily climate variability in order to
      estimate the consequences on human health vulnerability in the context of global
      climate change. Information related to medical consultations for allergic
      rhinitis due to pollen comes from the Quebec Health Insurance Board (Regie de
      l'assurance-maladie du Quebec). Ambrosia pollen concentration was measured by the
      Aerobiology Research Laboratories (Nepean, Ontario). Daily temperature (maximum,
      minimum, and mean) and precipitation data were obtained from the Meteorological
      Service of Canada. Socio-economic data come from the 1996 and 2001 census data of
      Statistics Canada. Between 1994 and 2002, during the Ambrosia pollen season, 7667
      consultations for allergic rhinitis due to pollen were recorded. We found a
      significant association between the number of medical consultations and pollen
      levels. Significant associations were detected for over-consultation the day of
      exposure, 1, 2, 3 and 5 days after exposure to high levels of pollen. The
      consultation rate is higher from low-income residents (3.10 consultations per
      10,000 inhabitants) than for high-income (1.65 consultations per 10,000
      inhabitants). Considering the demonstrated impact of pollen levels on health, it
      has become critical to ensure adequate monitoring of Ambrosia and its
      meteorological sensivity in the context of the anticipated climate change and its
      potential consequences on human health.

PMID- 16899281
TI  - Arsenic groundwater contamination and its health effects in the state of Uttar
      Pradesh (UP) in upper and middle Ganga plain, India: a severe danger.
AB  - This communication presents results of our 2-year survey on groundwater arsenic
      contamination in three districts Ballia, Varanasi and Gazipur of Uttar Pradesh
      (UP) in the upper and middle Ganga plain, India. Analyses of 4,780 tubewell water
      samples revealed that arsenic concentrations in 46.5% exceeded 10 microg/L, in
      26.7%, 50 microg/L and in 10% 300 microg/L limits. Arsenic concentrations up to
      3,192 microg//L were observed. The age of tubewells (n=1,881) ranged from less
      than a year to 32 years, with an average of 6.5 years. Our study shows that older
      tubewells had a greater chance of contamination. Depth of tubewells (n=3,810)
      varied from 6 to 60.5 m with a mean of 25.75 m. A detailed study in three
      administrative units within Ballia district, i.e. block, Gram Panchayet, and
      village was carried out to assess the magnitude of the contamination. Before our
      survey the affected villagers were not aware that they were suffering from
      arsenical toxicity through contaminated drinking water. A preliminary clinical
      examination in 11 affected villages (10 from Ballia and 1 from Gazipur district)
      revealed typical arsenical skin lesions ranging from melanosis, keratosis to
      Bowens (suspected). Out of 989 villagers (691 adults, and 298 children) screened,
      137 (19.8%) of the adults and 17 (5.7%) of the children were diagnosed to have
      typical arsenical skin lesions. Arsenical neuropathy and adverse obstetric
      outcome were also observed, indicating severity of exposure. The range of arsenic
      concentrations in hair, nail and urine was 137-10,900, 764-19,700 microg/kg, and
      23-4,030 microg/L, respectively. The urine, hair and nail concentrations of
      arsenic correlated significantly (r=0.76, 0.61, and 0.55, respectively) with
      drinking water arsenic concentrations. The similarity to previous studies on
      arsenic contamination in West Bengal, Bihar and Bangladesh indicates that people
      from a significant part of the surveyed areas in UP are suffering and this will
      spread unless drives to raise awareness of arsenic toxicity are undertaken and an
      arsenic safe water supply is immediately introduced.

PMID- 16899282
TI  - Heavy coal combustion as the dominant source of particulate pollution in Taiyuan,
      China, corroborated by high concentrations of arsenic and selenium in PM10.
AB  - Coal burning generates toxic elements, some of which are characteristic of coal
      combustion such as arsenic and selenium, besides conventional coal combustion
      products. Airborne particulate samples with aerodynamic diameter less than 10
      microm (PM(10)) were collected in Taiyuan, China, and multi-element analyses were
      performed by inductively coupled plasma atomic emission spectrometry (ICP-AES)
      and inductively coupled plasma mass spectrometry (ICP-MS). Concentrations of
      arsenic and selenium from ambient air in Taiyuan (average 43 and 58 ng m(-3),
      respectively) were relatively high compared to what is reported elsewhere.
      Arsenic and selenium were found to be highly correlated (r=0.997), indicating an
      overwhelmingly dominant source. Correlation between these two chalcophile
      elements and the lithophile element Al is high (r is 0.75 and 0.72 for As and Se,
      respectively). This prompted the hypothesis that the particles were from coal
      combustion. The enrichment of the trace elements could be explained by the
      volatilization-condensation mechanism during coal combustion process. Even higher
      correlations of arsenic and selenium with PM(10) (r=0.90 and 0.88) give further
      support that airborne particulate pollution in Taiyuan is mainly a direct result
      of heavy coal consumption. This conclusion agrees with the results from our
      previous study of individual airborne particles in Taiyuan.

PMID- 16899283
TI  - Stromal differences in salivary gland tumors of a common histopathogenesis but
      with different biological behavior: a study with picrosirius red and polarizing
      microscopy.
AB  - Salivary gland neoplasms - pleomorphic adenoma, polymorphous low-grade
      adenocarcinoma, and adenoid cystic carcinoma - share a common histogenetic trait,
      but differ markedly in their biological properties. The objective of the study
      was to assess the polarization colors of picrosirius red-stained stromal collagen
      fibers in these salivary gland neoplasms to evaluate their possible role in the
      histopathogenesis of the tumors and to evaluate the potential usefulness of this
      approach as a diagnostic tool. Ten cases of each tumor type and 10 cases of
      mucous extravasation phenomenon (control) were examined using picrosirius red
      staining and polarizing microscopy. In each case, at least 50 thin (
      approximately 0.8 microm) and 50 thick (1.6-2.4 microm) collagen fibers were
      counted and classified as green-yellow or yellow-orange, the mean percentage was
      calculated and statistical differences analyzed by one-way ANOVA. Results showed
      a similar thin fiber distribution in all tumor types and controls (82-88% green
      yellow, 12-18% yellow-orange, p>0.05). Thick fibers showed a different
      distribution in polymorphous low-grade adenocarcinoma and adenoid cystic
      carcinoma (approximately 50% green-yellow) compared to pleomorphic adenoma and
      mucous extravasation phenomenon (approximately 13% green-yellow) (p=0.001). Thick
      fiber distribution was similar in polymorphous low-grade adenocarcinoma and
      adenoid cystic carcinoma (p>0.05). We conclude that with picrosirius red staining
      and polarizing microscopy, stromal collagen fibers differ significantly in
      pleomorphic adenoma from those in polymorphous low-grade adenocarcinoma and
      adenoid cystic carcinoma, but not from mucous extravasation phenomenon.
      Similarity between polymorphous low-grade adenocarcinoma and adenoid cystic
      carcinoma may indicate that these tumor types represent a single entity with a
      broad spectrum of biological behavior.

PMID- 16899284
TI  - Ethological comparison of the effects of a bovine alpha s1-casein tryptic
      hydrolysate and diazepam on the behaviour of rats in two models of anxiety.
AB  - A bovine alpha s1-casein tryptic hydrolysate was previously demonstrated to
      display an anxiolytic-like activity in the conditioned defensive burying and in
      the elevated plus-maze models when i.p. injected. The present study assessed the
      anxiolytic-like effects of this tryptic hydrolysate after an oral administration
      in rats faced to the same behavioural situations using diazepam as a reference.
      In a first experiment, the behavioural effects of the hydrolysate in the
      conditioned defensive burying test were investigated at doses ranging 5-50 mg/kg.
      The results showed that the minimal dose required to elicit an anxiolytic-like
      activity is 15 mg/kg. In a second experiment, the alpha s1-casein tryptic
      hydrolysate (15 mg/kg, p.o.) was demonstrated to display an anxiolytic-like
      activity similar to diazepam (3 mg/kg, p.o.) in the conditioned defensive burying
      test and the elevated plus-maze. However, the ethological analysis of behaviour
      indicated that this hydrolysate has a different activity compared to diazepam.
      While diazepam induced a disinhibition state in rats, possibly related to the
      risk-taking behaviour observed after a benzodiazepine ingestion in humans, the
      tryptic hydrolysate did not display such a side effect. These results suggest
      that the mechanism of action of the bovine alpha s1-casein tryptic hydrolysate
      may differ from that of diazepam.

PMID- 16899285
TI  - Rapid ethanol tolerance mediated by adaptations in acute tolerance in inbred
      mouse strains.
AB  - It has been postulated that decreased acute sensitivity to ethanol is an
      important genetically-mediated risk factor for the development of alcoholism.
      Previous work in mice and rats has indicated that ethanol sensitivity can be
      reduced in a genotype-dependent manner by a single dose of ethanol 24 h prior to
      testing, so-called 'rapid' tolerance. The current studies were undertaken to
      determine if the observed rapid tolerance was mediated by alterations in initial
      sensitivity or acute functional tolerance (AFT), the two primary components of
      acute sensitivity. Separate groups of C57BL/6, DBA/2, ILS, and ISS inbred mouse
      strains were administered a single pretreatment dose of saline or ethanol (5
      g/kg). The original and modified versions of the loss of righting reflex test,
      ethanol-induced hypothermia, and ataxia on a stationary dowel rod were tested 24
      h later. Dependent on the test and strain, varying degrees of rapid tolerance
      were observed; a pronounced sensitization was detected in one case. There was a
      concomitant increase in the rate and/or magnitude of AFT with little change in
      initial sensitivity suggesting that rapid tolerance was mediated primarily by
      alterations in AFT. This conclusion may have implications for the contribution of
      acute sensitivity to human alcoholism.

PMID- 16899286
TI  - Pharmacological evidence for the participation of NO-cyclic GMP-PKG-K+ channel
      pathway in the antiallodynic action of resveratrol.
AB  - The possible participation of the nitric oxide (NO)-cyclic GMP-protein kinase G
      (PKG)-K+ channels pathway in the antiallodynic action of resveratrol and YC-1 in
      spinal nerve injured rats was assessed. Ligation of L5/L6 spinal nerves produced
      a clear-cut tactile allodynia in the rats. Intrathecal administration of
      resveratrol (100-600 microg) and 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole
      (0.1-2.7 microg, YC-1, a soluble guanylyl cyclase activator) decreased tactile
      allodynia induced by ligation of L5/L6 spinal nerves. Intrathecal treatment with
      NG-L-nitro-arginine methyl ester (10-100 microg, L-NAME, a NO synthase
      inhibitor), 1H-(1,2,4)-oxadiazolo(4,2-a)quinoxalin-1-one (1-10 microg, ODQ, a
      soluble guanylyl cyclase inhibitor), KT-5823 (5-500 ng, a PKG inhibitor) and
      iberiotoxin (5-500 ng, a large-conductance Ca2+ -activated K+ channel blocker),
      but not NG-D-nitro-arginine methyl ester (100 microg, D-NAME, an inactive isomer
      of L-NAME), glibenclamide (12.5-50 microg, ATP-sensitive K+ channel blocker) or
      vehicle, significantly diminished resveratrol (300 microg)- and YC-1 (2.7 microg)
      induced spinal antiallodynia. These effects were independent of prostaglandin
      synthesis inhibition as indomethacin did not affect resveratrol-induced
      antiallodynia. Results suggest that resveratrol and YC-1 could activate the
      proteins of the NO-cyclic GMP-PKG spinal pathway or large-conductance Ca2+ 
      activated, but not ATP-sensitive, K+ channels at the spinal cord in order to
      produce at least part of their antiallodynic effect in this model of neuropathy.

PMID- 16899287
TI  - Surveillance and assessment of workplace assault injuries: analysis of Rhode
      Island workers' compensation claims 1998-2002.
AB  - OBJECTIVE: To analyze workplace assault by rate, injury severity, and trends
      using Rhode Island workers' compensation claim data. METHOD: A total of 6402
      workers' compensation assault claims from Rhode Island for the period of 1998
      through 2002 was analyzed. Data from the U.S. Department of Labor was used to
      derive estimates of injury rates. RESULTS: An average rate of 27.7 assaults per
      10,000 workers was found and varied only marginally across years. Females filed
      75% of all assault claims, though injuries to males resulted in longer periods of
      indemnification. The total cost of workplace assaults was 7,025,997 dollars,
      averaging 1097 dollars per claim, and average indemnification duration was 16.8
      days per claim. While the assault rate was relatively stable, a notable decline
      in both cost and indemnification periods over time was discovered. CONCLUSION:
      The assault rate found was among the highest reported to date, demonstrating that
      workplace violence remains a significant threat to employee safety. While a
      decline in incident severity was discovered over time, many outcomes were still
      serious. Preventive interventions to reduce incidents of workplace assaults among
      groups at the highest risk should be given highest priority.

PMID- 16899288
TI  - The assessment of neurological systems with functional imaging.
AB  - In recent years a number of multivariate approaches have been introduced to map
      neural systems in health and disease. In this review, we focus on spatial
      covariance methods applied to functional imaging data to identify patterns of
      regional activity associated with behavior. In the rest state, this form of
      network analysis can be used to detect abnormal topographies reflecting regional
      changes in distributed neural systems. In activation experiments, this approach
      can be used to quantify network-performance relationships in normal and disease
      cohorts. Functional changes in the relevant neural systems are likely to underlie
      the behavioral abnormalities observed in a variety of disease and treatment
      conditions.

PMID- 16899289
TI  - Effect of exponential polymerization on color stability of resin-based filling
      materials.
AB  - PURPOSE: To investigate the influence of a halogen light curing device used with
      constant or exponential polymerization mode on the color stability of
      contemporary resin-based filling materials. MATERIALS AND METHODS: Eight samples
      of Charisma (CH), Durafill (DU), Definite (DE), and Dyract AP (DY) each were
      light-cured with constant power or with soft-start mode (Translux Energy) for 20,
      40 or 60s. The CIE-Lab-values (L(*), a(*), b(*)) were measured prior to and after
      performing dry aging, water aging or a Suntest (EN ISO 7491) and Delta L-, Delta
      a-, Delta b-, and Delta E-values were calculated. RESULTS: Statistical analysis
      (GLM and repetition of measures) showed significant changes (p<0.05) of the color
      values for each material's curing mode and time after each of the aging
      processes. Four-way ANOVA revealed significant differences (p<0.05) between Delta
      L-, Delta a-, Delta b-, and Delta E of the materials in dependence on the curing
      time and mode and aging condition. Exponentially-cured DU was the most color
      unstable material after aging in water followed by the 20s exponentially cured DE
      and CH samples. After the Suntest, DY showed significant bleaching (negative
      Delta b) and the largest Delta E for all curing times and modes followed by the
      DE samples. DU and CH were the most color-stable materials in this test.
      SIGNIFICANCE: The extent of discoloration depends on the (a) curing time, (b)
      curing mode, (c) aging condition, and (d) material. For the constant curing mode,
      40s curing time for the exponential 60s seems to be appropriate.

PMID- 16899290
TI  - Fingerprinting petroleum hydrocarbons in plankton and surface sediments during
      the spring and early summer blooms in the Galician coast (NW Spain) after the
      Prestige oil spill.
AB  - Plankton samples (20-350 microm and >350 microm) collected at three transects
      along the Galician coast (NW Spain) were analysed for individual aliphatic and
      aromatic hydrocarbons by GC-MS. Sample collection was performed in April-July
      2003, after the Prestige oil spill (November 2002), to determine whether the
      hydrocarbons released into the water column as a consequence of the spill were
      accumulated by the planktonic communities during the subsequent spring and early
      summer blooms. Surface sediments were also collected to assess the presence of
      the spilled oil, removed from the water column by downward particle transport.
      Plankton concentrations of PAHs (Sigma14 parent components) were in the range of
      25-898 ng g(-1)dw, the highest values being close to coastal urban areas.
      However, the individual distributions were highly dominated by alkyl naphthalenes
      and phenanthrenes, paralleling those in the water dissolved fraction. The
      detailed study of petrogenic molecular markers (e.g. steranes and triterpanes,
      and methyl phenanthrenes and dibenzothiophenes) showed the occurrence of
      background petrogenic pollution but not related with the Prestige oil, with the
      possible exception of the station off Costa da Morte in May 2003, heavily oiled
      after the accident. The dominant northerly wind conditions during the spring and
      early summer 2003, which prevented the arrival of fresh oil spilled from the
      wreck, together with the heavy nature of the fuel oil, which was barely dispersed
      in seawater, and the large variability of planktonic cycles, could be the factors
      hiding the acute accumulation of the spilled hydrocarbons. Then, with the above
      exception, the concentrations of PAHs found in the collected samples, mostly
      deriving from chronic pollution, can be considered as the reference values for
      the region.

PMID- 16899291
TI  - Kinetin--a multiactive molecule.
AB  - Cytokinins are important adenine derivatives that serve as hormones to control
      many processes in plants. They were discovered as factors that promote cell
      division in tobacco tissue cultures and have been shown also to regulate several
      other developmental events. Kinetin which was isolated 50 years ago for the first
      time as a plant hormone, as well as other cytokinins isopentenyladenine, zeatin
      and benzylaminopurine induce callus (clusters of dedifferentiated plant cells) to
      redifferentiate into adventitious buds. Because of some similarities in the
      biological phenotypes of cancer and callus cells, cytokinins and especially
      kinetin, affect the differentiation of human cells through a common signal
      transduction system. Therefore, cytokinins found their way to use in molecular
      medicine.

PMID- 16899293
TI  - The value of Seasonal Correction Factors in assessing the health risk from
      domestic radon: a case study in Northamptonshire, UK.
AB  - Following an intensive survey of domestic radon levels in the United Kingdom
      (UK), the former National Radiological Protection Board (NRPB), now the Radiation
      Protection Division of the Health Protection Agency (HPA-RPD), established a
      measurement protocol and promulgated Seasonal Correction Factors applicable to
      the country as a whole. Radon levels in the domestic built environment are
      assumed to vary systematically and repeatably during the year, being generally
      higher in winter. The Seasonal Correction Factors therefore comprise a series of
      numerical multipliers, which convert a 1-month or 3-month radon concentration
      measurement, commencing in any month of the year, to an effective annual mean
      radon concentration. In a recent project undertaken to assess the utility of
      short-term exposures in quantifying domestic radon levels, a comparative
      assessment of a number of integrating detector types was undertaken, with radon
      levels in 34 houses on common geology monitored over a 12-month period using dose
      integrating track-etch detectors exposed in pairs (one upstairs, one downstairs)
      at 1-month and 3-month resolution. Seasonal variability of radon concentrations
      departed significantly from that expected on the basis of the HPA-RPD Seasonal
      Correction Factor set, with year-end discontinuities at both 1-month and 3-month
      measurement resolutions. Following this study, monitoring with electrets was
      continued in four properties, with weekly radon concentration data now available
      for a total duration in excess of three and a half years. Analysis of this data
      has permitted the derivation of reliable local Seasonal Correction Factors.
      Overall, these are significantly lower than those recommended by HPA-RPD, but are
      comparable with other results from the UK and from abroad, particularly those
      that recognise geological diversity and are consequently prepared on a regional
      rather than a national basis. This finding calls into question the validity of
      using nationally aggregated Seasonal Correction Factors, especially for shorter
      exposures, and the universal applicability of these corrections is discussed in
      detail.

PMID- 16899292
TI  - Elastogenic effects of exogenous hyaluronan oligosaccharides on vascular smooth
      muscle cells.
AB  - Prior studies suggest that hyaluronan (HA), a glycosaminoglycan, may upregulate
      innately poor elastin matrix synthesis by adult vascular smooth muscle cells
      (SMCs). HA scaffolds could thus be useful to regenerate damaged vascular elastin.
      In an earlier study, we established that the elastogenic effects of non
      oligomeric HA are fragment size- and/or dose-specific. We currently investigate
      the pro-elastogenic effects of exogenous HA oligomers on rat aortic smooth muscle
      cells (RASMCs). RASMCs were cultured with pure HA oligomers (4-mers) and mixtures
      (4-8mers) obtained by enzymatic digestion of long-chain HA (MW approximately
      2000kDa). Polyacrylamide gel electrophoresis (PAGE)/Matrix Assisted Laser
      Desorption/Ionization Spectroscopy Time-Of-Flight Analysis (MALDI-TOF) showed HA
      digestates to contain a mixture of 4-8mers with a predominance of 4-mers (75+/
      0.4% w/w). Cell layers supplemented with both pure HA 4-mers or oligomer mixtures
      showed proliferation levels similar to non-HA controls over 21 days of culture.
      Pure 4-mers and oligomer mixtures enhanced DNA-normalized output of tropoelastin
      by 1.6 and 1.8 times, respectively, and that of matrix elastin by approximately
      2.7 times relative to controls. Sodium dodecyl sulfate (SDS)-PAGE/Western Blot
      and a desmosine assay semi-quantitatively confirmed the observed biochemical
      trends for tropoelastin and matrix elastin, respectively. HA oligomers induced
      enhanced synthesis of the elastin crosslinker, desmosine, and appeared to
      stabilize the elastin matrix by suppression of elastin-laminin receptor (ELR)
      activity relative to controls. Transmission electron micrographs (TEMs) showed
      elastin deposits within oligomer-supplemented cultures to be distinct,
      longitudinally oriented, aggregating fibrils, and clumps, and to be less abundant
      and mostly amorphous in controls. HA oligomers preserved normal fibrillin
      mediated elastin matrix deposition. Results suggest that HA oligos are highly pro
      elastogenic, promote elastin fibril formation, and stabilize elastin matrix and
      may thus be usefully incorporated into scaffolds for guided elastin regeneration.

PMID- 16899294
TI  - The legacy of past manuring practices on soil contamination in remote rural
      areas.
AB  - This paper demonstrates that there can be a legacy of contamination on former
      arable land in remote rural areas as a result of past manuring practices. In the
      first part of the study four farms abandoned in the late 19th to mid-20th century
      were investigated with samples collected from residual material in domestic
      hearths, the midden heaps, kailyards (walled garden for vegetables), infields
      (intensively managed arable land) and outfields (less intensively managed land
      for cropping or grazing). Consistent sequences in concentration values were found
      for such elements as Pb, Zn, Cu and P in the order
      hearth>midden>kailyard>infield>outfield. Such patterns can in part be explained
      in terms of atmospheric deposition on peat and turf which were subsequently burnt
      in hearths to result in enhanced elemental concentrations. The ash then was
      deposited in midden heaps and subsequently on kailyards or infields. In the
      second part, microanalytical results from St. Kilda are discussed. Enhanced
      loadings of Pb and Zn were found in the old arable land. The highest levels of Zn
      were found in small fragments of carbonised and humified material and bone
      fragments; in contrast Pb tended to be more uniformly distributed. Seabird waste
      was extensively applied to the arable land and some of the Zn may have
      accumulated in the soil by this pathway. The retention of Zn in bone is likely to
      have been very minor given the rarity of bone fragments as evident in thin
      sections (0.3%); this compares with 6.8% for black carbonised particles which are
      likely to provide the main storage sites for Zn.

PMID- 16899295
TI  - The risk assessment-policy gap: an example from the UK contaminated land regime.
AB  - Risk-based regulation assumes that risk assessment can evaluate risks against
      policy objectives. However, policy goals are often ambiguous and require risk
      assessors to interpret them for use in risk assessment. This risk assessment
      policy gap stems partly from normative and imprecise policy language but is
      rooted more fundamentally in society's uncertain expectations for the
      environment. Until this uncertainty is resolved, the democratic and regulatory
      effectiveness of risk regulation will be undermined by ad hoc policy decisions
      abdicated to risk assessors.

PMID- 16899297
TI  - Phosphate group effects upon the equilibrium of iron(III) meso-tetrakis (4-N
      methylpyridiniumyl) porphyrin in aqueous solution.
AB  - Iron(III) meso-tetrakis (4-N-methylpyridiniumyl) porphyrin (FeTMPyP) undergoes a
      complex equilibrium in aqueous solution as a function of pH. Use of phosphate
      buffers, a common practice in biomedical applications of porphyrins, suggests the
      complexation of phosphate anion at the sixth coordination position to the iron,
      which contributes to the complexity of the equilibrium in the pH range from 1 to
      4. In the absence of phosphate the equilibrium is simplified in a similar way as
      in the presence of high salt concentrations. Combined use of optical absorption,
      (1)H NMR and infrared spectroscopies, together with the literature data, suggest
      the formation of hexacoordinated monoaqueous-phosphate FeTMPyP complex in a
      limited acidic pH range. Discussion of the behavior of cationic FeTMPyP as
      compared to anionic iron(III) meso-tetrakis (4-sulfonatophenyl) porphyrin
      (FeTPPS(4)) is presented in regard to equilibrium of different species to explain
      the observed complex equilibrium.

PMID- 16899296
TI  - Interactions of 1,12-diamino-4,9-dioxadodecane (OSpm) and Cu(II) ions with
      pyrimidine and purine nucleotides: adenosine-5'-monophosphate (AMP) and cytidine
      5'-monophosphate (CMP).
AB  - The interactions of Cu(II) ions with adenosine-5'-monophosphate (AMP), cytidine
      5'-monophosphate (CMP) and 1,12-diamino-4,9-dioxadodecane (OSpm) were studied. A
      potentiometric method was applied to determine the composition and stability
      constants of complexes formed, while the mode of interactions was analysed by
      spectral methods (ultraviolet and visible spectroscopy (UV-Vis), electron
      paramagnetic resonance (EPR), (13)C NMR, (31)P NMR). In metal-free systems,
      molecular complexes nucleotide-polyamine (NMP)H(x)(OSpm) were formed. The
      endocyclic nitrogen atoms of the purine ring N(1), N(7), the nitrogen atom of the
      pyrimidine ring N(3), the oxygen atoms of the phosphate group of the nucleotide
      and the protonated nitrogen atoms of the polyamine were the reaction centres. The
      mode of interaction of the metal ion with OSpm and the nucleotides (AMP or CMP)
      in the coordination compounds was established. In the system Cu(II)/OSpm the
      dinuclear complex Cu(2)(OSpm) forms, while in the ternary systems
      Cu(II)/nucleotide/OSpm the species type MH(x)LL' and MLL' appear. In the MH(x)LL'
      type species, the main centres of copper (II) ion binding in the nucleotide are
      the phosphate groups. The protonated amino groups of OSpm are involved in non
      covalent interaction with the nitrogen atoms N(1), N(7) or N(3) of the purine or
      pyrimidine ring, whereas at higher pH, deprotonated nitrogen atoms of polyamine
      are engaged in metallation in MLL' species.

PMID- 16899298
TI  - Bioinorganic transformations of liver iron deposits observed by tissue magnetic
      characterisation in a rat model.
AB  - The magnetic properties and the ultrastructure, with special emphasis on the
      nanometric range, of liver tissues in an iron overload rat model have been
      investigated. The tissues of the animals, sacrificed at different times after a
      single iron dextran injection, have been characterised by magnetic AC
      susceptibility measurements together with transmission electron microscopy (TEM)
      and selected area electron diffraction (SAED) as helping techniques. It has been
      observed that few days after the iron administration the liver contains at least
      two iron species: (i) akaganeite nanoparticles, coming from iron dextran and (ii)
      ferrihydrite nanoparticles corresponding to ferritin. The magnetic susceptibility
      of the tissues depends not only on the elemental iron content but also on its
      distribution among chemical species, and varies in a remarkable regular manner as
      a function of the elapsed time since the iron administration. The results are of
      relevance with respect to non-invasive techniques for liver iron determination,
      directly or indirectly based on the magnetic susceptibility of the tissues, as
      biomagnetic liver susceptometry (BLS) and magnetic resonance (MRI) image
      treatment.

PMID- 16899299
TI  - Flexible multielectrodes can resolve multiple muscles in an insect appendage.
AB  - Research into the neuromechanical basis of behavior, either in biomechanics,
      neuroethology, or neuroscience, is frequently limited by methods of data
      collection. Two of the most pressing needs are for methods with which to (1)
      record from multiple neurons or muscles simultaneously and (2) perform this
      recording in intact, behaving animals. In this paper we present the fabrication
      and testing of flexible multielectrode arrays (fMEAs) that move us significantly
      towards these goals. The fMEAs were used to record the activity of several
      distinct units in the coxa of the cockroach Blaberus discoidalis. The devices
      fabricated here address the first goal in two ways: (1) their flexibility allows
      them to be inserted into an animal and guided through internal tissues in order
      to access distinct groups of neurons and muscles and (2) their recording site
      geometry has been tuned to suit the anatomy under study, yielding multichannel
      spike waveforms that are easily separable under conditions of spike overlap. The
      flexible nature of the devices simultaneously addresses the second goal, in that
      it is less likely to interfere with the natural movement of the animal.

PMID- 16899300
TI  - A rat brain slice preparation for characterizing both thalamostriatal and
      corticostriatal afferents.
AB  - The striatum, the primary input nucleus of the basal ganglia, is crucially
      involved in motor and cognitive function and receives significant glutamate input
      from the cortex and thalamus. Increasing evidence suggests fundamental
      differences between these afferents, yet direct comparisons have been lacking. We
      describe a slice preparation that allows for direct comparison of the
      pharmacology and biophysics of these two pathways. Visualization of slices from
      animals previously injected with BDA into the parafascicular nucleus revealed the
      presence of axons of thalamic origin in the slice. These axons were especially
      well-preserved after traversing the reticular nucleus, the location chosen for
      stimulation of thalamostriatal afferents. Initial characterization of the two
      pathways revealed both non-NMDA and NMDA receptor-mediated currents at synapses
      from both afferents and convergence of the afferents in 51% of striatal efferent
      neurons. Annihilation of action potentials was not observed in collision
      experiments, nor was current spread from the site of stimulation to striatum
      found. Differences in short-term plasticity suggest that the probability of
      release differs for the two inputs. The present work thus provides a novel rat
      brain slice preparation in which the effects of selective stimulation of cortical
      versus thalamic afferents to striatum can be studied in the same preparation.

PMID- 16899301
TI  - A systematic review of randomized controlled trials of acupuncture in the
      treatment of depression.
AB  - BACKGROUND: Acupuncture has become a popular complementary and alternative
      treatment approach. This review examined the randomized controlled trials (RCTs)
      examining the effects of acupuncture treatment of depression. METHODS: RCTs of
      the treatment of depression with acupuncture were located using MEDLINE, Allied
      and Complementary Medicine and the Cochrane Central Register of Controlled
      Trials. The methodology of RCTs was assessed using the Jadad criteria, and
      elements of research design, i.e., randomization, blinding, assessment of
      attrition rates, were quantified for systematic comparisons among studies.
      RESULTS: Among the 9 RCTs examined, five were deemed to be of low quality based
      upon Jadad criteria. The odds ratios derived from comparing acupuncture with
      control conditions within the RCTs suggests some evidence for the utility of
      acupuncture in depression. General trends suggest that acupuncture modalities
      were as effective as antidepressants employed for treatment of depression in the
      limited studies available for comparison. However, placebo acupuncture treatment
      was often no different from intended verum acupuncture. LIMITATIONS: The RCTs
      extracted were limited by small sample sizes, imprecise enrollment criteria,
      problems with randomization, blinding, brief duration of study and lack of
      longitudinal follow-up. CONCLUSIONS: Despite the findings that the odds ratios of
      existing literature suggest a role for acupuncture in the treatment of
      depression, the evidence thus far is inconclusive. However, efforts are being
      made to standardize complementary approaches to treat depression, and further
      systematized research into their use is warranted.

PMID- 16899303
TI  - Is there a relationship between the detection of human herpesvirus 8 and Epstein
      Barr virus in Waldeyer's ring tissues?
AB  - OBJECTIVE: Human herpesvirus 8 (HHV-8) and Epstein-Barr virus (EBV) are human
      pathogens associated to a number of neoplasms, including tumors of the Waldeyer's
      ring. Both viruses have been previously detected by in situ methods in tonsils
      and adenoids from children. HHV-8 was found in 6.8% of the cases and EBV in about
      one third of the cases. As they belong to the same gamma-herpesvirus subfamily
      and share some biological characteristics, it is of medical interest to further
      explore their possible relationship in the Waldeyer's ring, an issue not yet
      addressed in the specialized literature. The purpose of the present study is to
      compare the presence of EBV by in situ hybridization (ISH) in tonsils and
      adenoids from children up to 14 years of age in cases previously shown to be
      positive and negative for HHV-8. METHODS: Paraffin wax-embedded sections
      consisting of 38 tonsils and two adenoids from 40 patients were analyzed. HHV-8
      was detected by ISH, using the T1-1 probe for the viral mRNA. EBV was also
      detected by ISH, using the EBER probe. Both probes and the detection systems were
      provided by Novocastra. RESULTS: HHV-8 was detected in 19 tonsils and one
      adenoid. The other 19 tonsils and one adenoid taken from the HHV-8-negative group
      were selected by pairing age and gender of patients with the HHV-8-positive
      group. In both groups EBV was detected in 13 cases and was negative in other 7.
      CONCLUSION: Although both viruses are related in many aspects, some biological
      and epidemiological features differ. This is reflected in the present results, as
      EBV is similarly detected in the groups negative and positive for HHV-8, favoring
      different mechanisms of spread.

PMID- 16899302
TI  - Deficient Fas expression by CD4+ CCR5+ T cells in multiple sclerosis.
AB  - OBJECTIVE: To evaluate whether T cells expressing CCR5 and CXCR3 from multiple
      sclerosis (MS) patients are more resistant to apoptosis. METHODS: Expression of
      CD69, TNF-R1, Fas, FasL, bcl-2, and bax was investigated in 41 MS patients and 12
      healthy controls by flow cytometry in CD4+ and CD8+ T cells expressing CCR5 and
      CXCR3. RESULTS: In MS patients, the percentage of CD69 was increased and Fas
      expression decreased in CD4+ CCR5+ T cells. INTERPRETATION: The lower Fas
      expression in activated CD4+ CCR5+ T cells might contribute to disease
      pathogenesis by prolonging cell survival and favoring their migration into the
      CNS.

PMID- 16899304
TI  - Construction and characterization of a highly redundant Pseudomonas aeruginosa
      genomic library prepared from 12 clinical isolates: application to studies of
      gene distribution among populations.
AB  - OBJECTIVE: To create, array, and characterize a pooled, high-coverage, genomic
      library composed of multiple biofilm-forming clinical strains of the
      opportunistic pathogen, Pseudomonas aeruginosa (PA). Twelve strains were obtained
      from patients with otorrhea, otitis media, and cystic fibrosis as a resource for
      investigating: difference in the transcriptomes of planktonic and biofilm
      envirovars; the size of the PA supragenome and determining the number of
      virulence genes available at the population level; and the distributed genome
      hypothesis. METHODS: High molecular weight genomic DNAs from 12 clinical PA
      strains were individually hydrodynamically sheared to produce mean fragment sizes
      of approximately 1.5 kb. Equimolar amounts of the 12 sheared genomic DNAs were
      then pooled and used in the construction of a genomic library with approximately
      250,000 clones that was arrayed and subjected to quality control analyses.
      RESULTS: Restriction endonuclease and sequence analyses of 686 clones picked at
      random from the library demonstrated that >75% of the clones contained inserts
      larger than 0.5 kb with the desired mean insert size of 1.4 kb. Thus, this
      library provides better than 4.5x coverage for each of the genomes from the 12
      components clinical PA isolates. Our sequencing effort ( approximately 1 million
      nucleotides to date) reveals that 13% of the clones present in this library are
      not represented in the genome of the reference P. aeruginosa strain PA01.
      CONCLUSIONS: Our data suggests that reliance on a single laboratory strain, such
      as PA01, as being representative of a pathogenic bacterial species will fail to
      identify many important genes, and that to obtain a complete picture of complex
      phenomena, including bacterial pathogenesis and the genetics of biofilm
      development will require characterization of the P. aeruginosa population-based
      supra-genome.

PMID- 16899305
TI  - Otitic hydrocephalus associated with lateral sinus thrombosis and acute
      mastoiditis in children.
AB  - The incidence of intracranial complications of acute otitis media (AOM) has
      decreased and the need for operative and medical treatment is declined during the
      antibiotic era. To describe pathognomonic signs, evaluation management, operative
      findings, clinical course and outcome of otitic hydrocephalus and lateral sinus
      thrombosis as complications of AOM and mastoiditis in pediatric patients. Two
      children, 9 and 13 years old, with the diagnosis of OH and TK and MRI findings
      are presented. Intracranial complications in children resulted from unsuccessful
      treatment of AOM, which led to acute mastoiditis and lateral sinus thrombosis.
      Both of the presented children had thrombus in their sigmoid sinus
      preoperatively, demonstrated by MRI, causing decreased blood flow. Both patients
      underwent a mastoidectomy and delamination of sigmoid sinus with puncture of
      sinuses. After medical and surgical treatment, blood flow through the sinus
      increased significantly. In both cases signs of increased intracranial pressure
      ceased. The clinical presentation of otogenic lateral sinus thrombosis (LST) as a
      complication of acute otitis media (AOM) can be masked by antibiotic treatment.
      The episodes of vomiting, headache, visual impairment and a history of AOM seem
      to be indicative for otitic hydrocephalus. MRI scans of patients with similar
      symptoms should be carefully studied to facilitate the early diagnosis of dural
      sinus thrombosis with increased intracranial pressure. Contrast-enhanced computed
      tomography scan and magnetic resonance imaging play a major role in determining
      diagnosis and treatment plans in this intracranial complications. Management
      included systemic antibiotics, short-term heparin anticoagulation and surgical
      decompression. In our patients intensive i.v. antibiotic treatment, steroids,
      anticoagulants and surgery led to a significant improvement in the clinical
      condition.

PMID- 16899306
TI  - Resveratrol inhibition of varicella-zoster virus replication in vitro.
AB  - Resveratrol was found to inhibit varicella-zoster virus (VZV) replication in a
      dose-dependent and reversible manner. This decrease in virus production in the
      presence of resveratrol was not caused by direct inactivation of VZV or
      inhibition of virus attachment to MRC-5 cells. The drug effectively limited VZV
      replication if added during the first 30 h of infection. Western blot analysis
      and real-time RT-PCR studies demonstrated that protein and mRNA levels of IE62,
      an essential immediate early viral protein, were reduced when compared to
      controls. These results demonstrate that VZV replication is adversely affected by
      resveratrol which is negatively impacting IE62 synthesis.

PMID- 16899307
TI  - The influence of aging on recovery following ischemic brain damage.
AB  - Stroke is a health hazard that affects all age groups, however the impact of age
      on brain injury following ischemia remains largely unexamined. We examined the
      extent to which age, from the newborn to mature adult, affects behavioral
      recovery following similar degrees of ischemic brain damage. We utilized a model
      that produces comparable volumes of brain damage between the different ages.
      Endothelin-1, a potent vasoconstrictor, was injected into the brain of 10, 63 and
      180-day-old rats, at the level of the right middle cerebral artery. On days 3, 7,
      14, 28 and 56 post-insult, behavioral tests including rota-rod, foot-fault, open
      field, inclined screen, tape-removal test and postural reflex were performed.
      Control animals underwent sham surgery, but ischemia was not induced.
      Neuropathology was assessed on day 63 post-insult. Volume of damage was
      determined for each brain as a percentage of the contralateral hemisphere (which
      remains undamaged). Our results indicated that the volume of damage for each age
      group was 22.97, 19.97, and 18.85% for 10, 63 and 180-day-old rats, respectively,
      and were not significantly different from each other. Overall, ischemic animals
      did significantly more poorly on behavioral testing than did controls. When
      broken down by age, the difference between ischemics and controls was only
      evident in the 63 and 180-day-old animals. The tape-removal test revealed main
      effects of age, group, and day (p<0.001). In addition, significant interactions
      were noted for day of testing by age (p<0.001), day of testing by group with
      ischemics performing more slowly than controls, and an age by group interaction
      which indicated that the 63 and 180-day-old ischemic rats did not recover
      completely during the testing period and remained significantly slower than their
      controls (p<0.001). In the foot-fault task, the 63 and 180-day-old ischemic
      animals performed significantly more poorly on days 3, 7, and 14 of recovery,
      returning to control values by day 28. The 180-day olds performed more poorly on
      day 3 of recovery, but then returned to control values. For open-field testing,
      the results indicate an overall difference between ischemics and controls, with
      the 63 and 180-day-old animals improving with time though they did not achieve
      control values. In conclusion our data suggest functional performance is poorly
      and inconsistently correlated with the extent of morphologic injury across all
      age groups. The immature rat clearly recovers more completely and more rapidly
      than do older, more mature rats. The findings may imply a greater degree of brain
      plasticity in the infant rat compared to the adult, and have important
      implications related to the underlying mechanisms of recovery and the association
      between brain damage and functional improvement.

PMID- 16899308
TI  - Aquatic ecotoxicity of a pheromonal antagonist in Daphnia magna and Desmodesmus
      subspicatus.
AB  - Evaluation of the ecotoxicological potential of (Z)-11-hexadecenyl
      trifluoromethyl ketone (Z11-16:TFMK), a new biorational agent with high
      prospective features to control the Mediterranean corn borer Sesamia nonagrioides
      in infested maize fields, in comparison to the parent pheromone compound (Z)-11
      hexadecenyl acetate (Z11-16:Ac) is described. Acute and sublethal toxicity tests
      of both compounds against the cladoceran Daphnia magna and the chlorophyte
      Desmodesmus subspicatus were conducted, the endpoints being immobilisation and
      feeding inhibition for Daphnia and growth rate inhibition for Desmodesmus. In
      addition, effects on B esterases including cholinesterase and carboxylesterase
      activities in Daphnia were also assessed to evaluate the mode of action of both
      chemicals. Toxicities of both compounds were moderate with EC(50) values ranging
      from 3.11 to 103.74mgl(-1) in algae growth, from 0.07 to 1.20mgl(-1) in Daphnia
      survival, and from 0.10 to 0.53mgl(-1) in Daphnia feeding rate. In all cases Z11
      16:TFMK was more toxic than the naturally occurring pheromone component. Serine
      esterase assays showed a strong inhibition of the carboxylesterase activities in
      Daphnia at concentrations with apparently no effects on survival or feeding,
      suggesting that inhibition of other key esterases may be the possible mechanism
      of toxicity of this compound. The results obtained have been related with some
      physico-chemical properties of the compounds, such as water solubility and
      octanol-water partition coefficient, suggesting that Z11-16:TFMK may affect
      aquatic organisms at lower concentrations than expected from non-polar narcosis.

PMID- 16899309
TI  - Effect of spironolactone on C-reactive protein levels in patients with heart
      disease.
AB  - Animal evidence shows that aldosterone is pro-inflammatory and that aldosterone
      blockade is anti-inflammatory. Therefore part of the beneficial effect of
      aldosterone blockade that might contribute to it reducing mortality could be an
      anti-inflammatory effect. However, there are no previous data on whether
      aldosterone blockade is anti-inflammatory in man. We performed 4 separate studies
      to investigate whether spironolactone treatment would reduce levels of C-reactive
      protein (CRP), a marker of inflammation, in serum samples taken from patients
      suffering from different degrees of heart failure. We found in all 4 studies that
      spironolactone had no significant effect compared with placebo, on CRP levels in
      these patients. These studies provide evidence against the hypothesis that the
      clinical benefits produced by aldosterone blockade are due to it having anti
      inflammatory effects.

PMID- 16899310
TI  - Diabetes mellitus impairs myocardial oxygen metabolism even in non-infarct
      related areas in patients with acute myocardial infarction.
AB  - BACKGROUND: Although diabetes is associated with poor clinical outcomes after
      acute myocardial infarction, to date there have been no reports focusing on the
      myocardial oxygen metabolism in these patients. Thus, we evaluated the myocardial
      oxygen metabolism in patients with and without diabetes suffering from acute
      myocardial infarction using carbon-11 acetate positron emission tomography.
      METHODS: 20 patients (13 diabetic patients [group A] and 7 non-diabetic patients
      [group B]) underwent carbon-11 acetate positron emission tomography soon after
      the onset of acute myocardial infarction. The myocardial oxygen metabolism was
      evaluated within the infarct-related area and in the non infarct-related area. 6
      healthy volunteers (group C) and 6 diabetic patients without coronary artery
      disease (group D) also participated as controls. RESULTS: There were no
      significant differences in gender, age, infarct-related artery, peak level of
      serum creatine phosphokinase, left-ventricular ejection fraction at onset, or the
      defect severity on myocardial perfusion images between group A and group B. In
      group A, the clearance rate (Kmono) of carbon-11 acetate in infarct-related area
      (0.042+/-0.010) was not significantly different from that in group B (0.049+/
      0.016). In contrast, Kmono in non infarct-related area in group A (0.059+/-0.010)
      was significantly lower than that in group B (0.076+/-0.009; p=0.002), group C
      (0.072+/-0.004; p=0.026) and group D (0.078+/-0.005; p=0.001). CONCLUSIONS: These
      data indicate that the myocardial oxygen metabolism even in non infarct-related
      area in diabetic patients was impaired after the onset of acute myocardial
      infarction.

PMID- 16899311
TI  - Hydrochlorothiazide induced pulmonary oedema and alveolar epithelial ion
      transport.

PMID- 16899312
TI  - Plasma level of mitochondrial coupling factor 6 increases in patients with type 2
      diabetes mellitus.
AB  - Coupling factor 6 (CF6) is a novel endogenous inhibitor of prostacyclin. Plasma
      CF6 and 6-keto-PGF(1a) were measured by radioimmunoassay in 70 consecutively
      recruited patients with type 2 diabetes and in 56 healthy controls. A
      significantly increased plasma CF6 level was found in diabetics compared with
      controls. The CF6 level was inversely correlated with plasma 6-keto-PGF(1a) level
      and positively correlated with blood glucose and lipids. These results suggest
      that CF6 might be an obvious marker of impaired endothelium and might contribute
      to vascular damage in diabetes.

PMID- 16899313
TI  - Combination of electrocardiographic and angiographic markers of reperfusion in
      the prediction of infarct size in patients with ST-segment elevation myocardial
      infarction undergoing successful primary angioplasty.
AB  - BACKGROUND: Optimal epicardial recanalization does not guarantee optimal
      myocardial perfusion. The aim of the current study was to evaluate angiographic
      and electrocardiographic markers of reperfusion in the prediction of infarct size
      in patients with STEMI undergoing successful primary angioplasty. METHODS: Our
      population is represented by 270 STEMI patients with ST successful primary
      angioplasty (postprocedural TIMI 3 flow and residual stenosis <50%) with
      available corrected TIMI frame count (cTFC), myocardial blush grade (MBG), ST
      segment resolution and enzymatic infarct size (peak CK-MB) analyses. RESULTS: A
      significant linear relationship with enzymatic infarct size was observed for all
      markers of reperfusion, except for ST-segment resolution. These data were
      confirmed even when analyzed as continuous variables in case of cTFC (r=0.13,
      p=0.035), postprocedural residual cumulative ST-segment elevation (r=0.41,
      p<0.0001) and deviation (r=0.45, p<0.0001). At multivariate analysis applied to
      postprocedural angiographic and electrocardiographic markers of reperfusion,
      cumulative residual ST-segment deviation, myocardial blush grade, and corrected
      TIMI frame count were independent predictors of enzymatic infarct size.
      CONCLUSIONS: This study showed that, among patients with STEMI treated by primary
      angioplasty, cTFC, MBG and cumulative residual ST-segment deviation are
      independent predictors of infarct size. Therefore, angiography and
      electrocardiography may provide complementary information in the evaluation of
      myocardial perfusion.

PMID- 16899314
TI  - Intra-cardiac echocardiography guided trans-septal puncture in patients with
      dilated left atrium undergoing percutaneous transvenous mitral commissurotomy.
AB  - Percutaneous transvenous mitral commissurotomy (PTMC) is an effective treatment
      for mitral stenosis, but trans-septal puncture carries a certain risk of
      complications. There have been few reports on phase-array intra-cardiac
      echocardiography (ICE) guidance in trans-septal puncture for PTMC, especially in
      patients with dilated left atrium or distorted anatomy. Herein, we report our
      preliminary experience with ICE-guided trans-septal puncture in patients with
      dilated left atrium (>or=5.5 cm) who underwent PTMC. From June 2005 to March
      2006, there were nine consecutive patients with symptomatic mitral stenosis and
      left atrium size larger than 5.5 cm who underwent trans-septal puncture for PTMC
      with the ICE guidance in this institution by a same operator. The procedural and
      catheterization results were analyzed. Using ICE guidance, the success rate for
      trans-septal puncture was 100% for all patients with dilated left atrium (>or=5.5
      cm). The trans-septal procedures were free of major and minor complications and
      the patients were not exposed to contrast medium. Mitral valve area increased
      significantly from 1.0+/-0.2 cm(2) to 1.9+/-0.2 cm(2). Our preliminary result
      showed that ICE safely and effectively guided trans-septal puncture for PTMC in
      patients with dilated left atrium (>or=5.5 cm), thus eliminating contrast medium
      usage and avoiding unnecessary longer X-ray exposure.

PMID- 16899315
TI  - Factors associated with the clinical diagnosis of foot and mouth disease during
      the 2001 epidemic in the UK.
AB  - The purpose of this investigation was to identify factors associated with the
      clinical diagnosis of foot and mouth disease during the 2001 epidemic in the
      United Kingdom. Using logistic regression, we compared: (1) reports of suspect
      disease that resulted in the declaration of FMD to reports that did not, and (2)
      laboratory-positive cases to laboratory-negative cases. From 6,801 reports of
      suspect disease, 2,026 cases of FMD were identified. Suspect cases were more
      likely to become clinical cases if: (1) the report originated from the disease
      control authorities ('active surveillance') rather than the public, usually
      farmers ('passive surveillance'); (2) cattle were the species suspected of
      disease, as opposed to sheep; (3) the report was filed during the peak of the
      epidemic; (4) the reporting premises was within 3 km of an FMD case detected
      within the previous 2 weeks; or (5) the report originated from certain local
      disease control centres. There were significant two-way interactions between:
      type of surveillance and species suspected of disease, type of surveillance and
      proximity of other infected premises, species suspected and time in the epidemic,
      and time in the epidemic and proximity of other infected premises. Clinical cases
      were more likely to be laboratory positive if: (1) they were found by passive
      versus active surveillance, (2) cattle were suspected of disease (versus sheep),
      (3) oldest lesions were less than 3 days, (4) the report was filed at any time
      other than the peak of the epidemic, or (5) the report originated from certain
      local disease control centres. Significant two-way interactions were found
      between: type of surveillance and species suspected of disease, and type of
      surveillance and time in the epidemic.

PMID- 16899317
TI  - Neuroticism-Anxiety, Impulsive-Sensation Seeking and autonomic responses to
      somatosensory stimuli.
AB  - This study focused on autonomic responding in participants who scored high vs.
      low on the Neuroticism-Anxiety (N-Anx) and Impulsive-Sensation Seeking (Imp-SS)
      dimensions of the Zuckerman-Kuhlman Personality Questionnaire--Form III.
      Participants were presented with series of tones (standards, deviants and novels)
      and they received a mild electric shock (one, two or three pulses) at each 15th
      tone. Resting pre-stimulus skin conductance level (SCL) and heart rate (HR) level
      was recorded, as well as the skin conductance response (SCR) and (anticipatory)
      HR response to the electric stimuli. The autonomic measures differentiated
      between high- vs. low Imp-SS participants but failed to discriminate between high
      vs. low N-Anx participants, with the exception that high N-Anx participants
      showed smaller SCRs on some trials compared to the low N-Anx participants. High
      Imp-SS had a lower pre-stimulus SCL and smaller SCRs to deviant stimuli compared
      to low Imp-SS participants. Additionally, their HR acceleration was smaller in
      anticipation of the first and the deviant tones whereas their deceleratory
      response was larger relative to the HR changes observed for the low Imp-SS
      participants. This pattern of findings was taken to suggest that high Imp-SS
      participants are more arousable and less prone to defensive reactions to novel or
      aversive stimulation.

PMID- 16899316
TI  - Development of a perchlorate reductase-based biosensor for real time analysis of
      perchlorate in water.
AB  - Perchlorate (ClO4-) contamination of ground water is a widespread problem in the
      U.S., which can adversely affect human health and wildlife. Current methods for
      detecting and quantifying ClO4- in water are time consuming, expensive and
      sometimes subject to complex procedures. This study reports the construction of a
      ClO4- reductase-based biosensor for rapid determination of ClO4- in water. Using
      a 3 mm GCE (glass carbon electrode), a ClO4- sensing bio-electrode was
      constructed by coating an aliquot of a Dechlorosoma sp. ClO4- reductase on nafion
      (ion-exchange matrix) layer pre-coated on the polished surface of the GCE. The
      response time to ClO4- was approximately 111+/-28 s. Kinetic evaluation of the
      sensor response to ClO4- revealed linear increases (r2>99%) in 10 min with k
      values of 10.3, 24.2, 33.9 and 48.2 at 25, 50, 75 and 100 microg/L, respectively.
      A strong linear correlation was established between biosensor response (nA) and
      ion-chromatography conductivity readings (microS). Biosensor response to ClO4-
      was maximal at applied potential range of -0.6 to -1.0 V. ClO4- reduction was
      maximal in the range of 7.6 to 8.0. The ClO4- biosensor was significantly stable
      after repeated use (24 analyses conducted on day 1 over a 10-h period at room
      temperature). This study indicates great potential for the development of a
      portable biosensor for real time analysis of ClO4- in water.

PMID- 16899318
TI  - MR tracking of transplanted glial cells using poly-L-lysine-CF3.
AB  - Magnetic resonance (MR) imaging using super-paramagnetic iron oxides (SPIOs) is a
      powerful tool to monitor transplanted cells in living animals. Since, however,
      SPIOs are negative contrast agents, positive agents have been explored. In this
      study, we examined the feasibility of FITC-labeled poly-L-lysine-CF3 (PLK-CF3)
      using glial cells. FITC-labeled PLK-CF3 was easily internalized by neuroblastoma
      cells and glia as adding it into culture medium. No toxicity was seen at the
      concentration of less than 80 microg/ml. MR images positively detected labeled
      cells transplanted in the brain of living mouse. The results indicate that FITC
      labeled PLK-CF3 is a useful positive contrast agent for MR tracking.

PMID- 16899319
TI  - Genetic diversity of Gram-negative, proteolytic, psychrotrophic bacteria isolated
      from refrigerated raw milk.
AB  - The random amplified polymorphic DNA (RAPD) fingerprinting technique was used to
      assess the genetic diversity of 70 isolates of Gram-negative proteolytic
      psychrotrophic bacteria that were isolated from refrigerated raw milk. Three
      oligonucleotides, which generated 87 fragments of polymorphic DNA, were used in
      the amplification reactions. The genetic distance values calculated using
      Jaccard's coefficient showed there was high genetic variability among the
      isolates. Cluster analysis procedures suggested that the genetic variability
      among isolates belonging to the same species was as high as the variability among
      different species. Clustering by the UPGMA hierarchical method and data graph
      dispersion indicated a tendency of the isolates to group according to whether
      they did or did not ferment glucose.

PMID- 16899320
TI  - Properties of HPMA copolymer-doxorubicin conjugates with pH-controlled
      activation: effect of polymer chain modification.
AB  - Various conjugates of anticancer drug doxorubicin (DOX) covalently attached via
      hydrolytically degradable hydrazone bond to water-soluble N-(2
      hydroxypropyl)methacrylamide (HPMA) copolymer drug carriers were synthesized.
      Three types of precursors containing either positively or negatively charged
      groups or a hydrophobic substituent were employed. In vitro incubation of the
      conjugates in buffers showed relative stability at pH 7.4 (modelling blood) and a
      fast DOX release at pH 5 (modelling intracellular environment). The presence of
      carboxylic groups in the copolymer structure resulted in an increase in the DOX
      release rate of 15-20% while no effect of the introduction of positively charged
      groups was observed if compared with the unmodified conjugate. Self-assembling of
      the oleoyl groups-containing conjugate led into formation of polymeric micelles
      with high apparent molecular weight (M(w)=170,000) in aqueous solution and
      resulted in a decrease in the DOX release rate of approximately 20%. The
      cytostatic activity of the conjugates tested on several cancer cell lines was
      comparable with that of free DOX.HCl, depending on the sensitivity of a
      particular cell line to DOX. All the conjugates showed a much higher antitumour
      activity in vivo than the free drug tested in mice bearing EL4 T-cell lymphoma
      and treated using the therapeutic regime of drug administration. The highest
      activity (100% long-term survivors) exhibited polymer-DOX conjugate containing
      negatively charged GFLG sequences.

PMID- 16899321
TI  - Hepatic histology in obese patients undergoing bariatric surgery.
AB  - BACKGROUND/AIMS: Obesity is one of the most important clinical associations with
      non-alcoholic steatohepatitis (NASH). Our aim was to assess the prevalence of non
      alcoholic fatty liver disease (NAFLD)/NASH in morbidly obese patients and the
      risk factors to more aggressive liver disease in this population. METHODS: Review
      of available studies on prevalence of NAFLD/NASH in severely obese patients
      submitted to bariatric surgery. RESULTS: Twelve observational and transversal
      studies were included, with consecutive recruitment, and prospective evaluation
      of data, summing 1620 patients with severe obesity. Prevalence of steatosis and
      NASH was 91% (range: 85-98%) and 37% (24-98%), respectively, with unexpected
      cirrhosis in 1.7% (1-7%). NASH was not related with age or body mass index, but
      there was an association between male sex and NASH/hepatic fibrosis. Diabetes
      mellitus and insulin resistance were the conditions most frequently associated
      with NASH, and hypertension with advanced hepatic fibrosis. CONCLUSIONS: There is
      a very high prevalence of NAFLD in asymptomatic morbidly obese patients, more
      than one-third presenting histological criteria for NASH. This review underscores
      the large variations in prevalence of NASH between studies, calling for the need
      for a better agreement in the use of the histological criteria.

PMID- 16899322
TI  - The hepatopulmonary syndrome.

PMID- 16899323
TI  - Autoimmune hepatitis (AIH) in the elderly: a systematic retrospective analysis of
      a large group of consecutive patients with definite AIH followed at a tertiary
      referral centre.
AB  - BACKGROUND/AIMS: A few reports have suggested that AIH may be less severe in the
      elderly and may be underdiagnosed, but there is a paucity of data. METHODS: We
      have undertaken a systematic analysis of 164 consecutive patients (36 males, 128
      females) with definite AIH (median score 23, range 18-28) attending our clinics,
      comparing those presenting at age >60 years (Group 1, n=43) with those presenting
      at <60 years (Group 2, n=121). RESULTS: Median (range) duration of follow-up was
      9 years (1-28) in Group 1 and 14 years (1-33) in Group 2. Median ages (ranges) at
      presentation were: Group 1=65 (60-79) and Group 2=41 (6-59). Group 1 patients had
      a significantly increased incidence of ascites at presentation (p<0.001) and a
      lower incidence of relapse (42% vs. 70%, p=0.002), but there were no significant
      differences between the groups with respect to mode of onset (acute, insidious,
      asymptomatic), other clinical signs at presentation, biochemical parameters,
      types or titres of autoantibodies, incidence of histological cirrhosis, response
      to therapy or related side effects. There were also no significant differences in
      liver-related deaths or transplantation, or the frequencies of HLA DR3 or DR4 -
      although there was an increased frequency of the A1-B8-DR3/4 haplotype in Group 2
      (40% vs. 22%, p=0.138). CONCLUSIONS: These findings suggest that AIH often
      presents in older patients, who frequently have severe disease. Active management
      in these patients can lead to a normal life expectancy.

PMID- 16899324
TI  - Does hospital cleanliness correlate with methicillin-resistant Staphylococcus
      aureus bacteraemia rates?
AB  - Publicly available data for all National Health Service hospitals in England were
      used to examine whether there is a link between hospital cleanliness and rates of
      meticillin-resistant Staphylococcus aureus (MRSA) bacteraemia. It was not
      possible to demonstrate a consistent relationship between hospital cleanliness,
      as measured by weighted Patient Environment Action Team (PEAT) scores, and the
      incidence of MRSA bacteraemia. The large sizes of the data sets make it unlikely
      that a true correlation was missed. While a high standard of hospital cleanliness
      is a worthwhile goal, it is not helpful to repeatedly link MRSA control measures
      with improvements in standards of environmental cleanliness.

PMID- 16899326
TI  - Critique of a FDA-CDC public health advisory that discusses inadequate automated
      bronchoscope reprocessing.

PMID- 16899325
TI  - Reduction of surgical site infections after Caesarean delivery using
      surveillance.
AB  - Since 1997, the Krankenhaus Infektions Surveillance System (KISS) has collected
      data on surgical site infections (SSIs) following Caesarean delivery (CD). The
      aim of this study was to determine whether surveillance and feedback of
      healthcare-associated infections (HAIs) could reduce the infection rate after CD.
      Only departments that had participated in KISS for at least three years were
      included in the analysis. The CD infection rates of the first, second and third
      years of KISS participation were compared for significant differences. The
      relative risk was calculated for the first and the third year of KISS
      participation. Multi-variate logistic regression analysis was performed to detect
      significant risk factors for SSI after CD using the third year of participation
      as one parameter. Twenty-six of 52 obstetric and gynaecology departments met the
      study's inclusion criteria. In those 26 departments, 17,405 CD procedures were
      performed and 331 SSIs were recorded (1.9%). The SSI rate after CD procedures was
      significantly reduced in the third year of KISS participation (1.6%) compared
      with the first year of KISS participation (2.4%), with a relative risk of 0.63
      [95% confidence interval (CI) 0.48-0.82]. Logistic regression analysis confirmed
      that KISS participation over three years was an independent factor for the
      reduction of SSI rate (odds ratio 0.64; 95% CI 0.49-0.83). As shown previously
      for other types of HAI, this study demonstrated that continuous surveillance and
      comparison with stratified reference data could reduce SSI infection rates after
      CD.

PMID- 16899328
TI  - Air quality impacts of power plant emissions in Beijing.
AB  - The CALMET/CALPUFF modeling system was applied to estimate the air quality
      impacts of power plants in 2000 and 2008 in Beijing, and the intake fractions
      (IF) were calculated to see the public health risks posed. Results show that in
      2000 the high emission contribution induced a relatively small contribution to
      average ambient concentration and a significant impact on the urban area (9.52
      microg/m(3) of SO(2) and 5.29 microg/m(3) of NO(x)). The IF of SO(2), NO(x) and
      PM(10) are 7.4 x 10(-6), 7.4 x 10(-6) and 8.7 x 10(-5), respectively. Control
      measures such as fuel substitution, flue gas desulfurization, dust control
      improvement and flue gas denitration planned before 2008 will greatly mitigate
      the SO(2) and PM(10) pollution, especially alleviating the pressure on the urban
      area to reach the National Ambient Air Quality Standard (NAAQS). NO(x) pollution
      will be mitigated with 34% decrease in concentration but further controls are
      still needed.

PMID- 16899327
TI  - An outbreak of wound infection in cardiac surgery patients caused by Enterobacter
      cloacae arising from cardioplegia ice.
AB  - This paper describes an outbreak of postoperative sternal wound infections. A
      cardiac surgeon noted a cluster of serious infections leading to wound
      dehiscence, despite the fact that none of his colleagues had noticed a rise in
      infection rates. The infections were predominantly with Enterobacter cloacae, and
      molecular typing and serotyping showed these isolates to be indistinguishable.
      Observation of the surgeon's practice revealed nothing untoward, and there were
      no infections among his patients operated on in another hospital. There appeared
      to be no significant difference between the modes of operation of the different
      surgeons. The operating theatres were screened to exclude an environmental
      source, with samples cultured on CHROMagar Orientation, a selective/differential
      medium designed for urine samples. Further questioning revealed one difference
      between the practices of the different surgeons; this surgeon used semi-frozen
      Hartmann's solution to achieve cardioplegia. The freezer used for this was
      swabbed and yielded E. cloacae, indistinguishable from the clinical isolates. It
      is hypothesized that this organism contaminated the freezer, and that the
      contamination was passed on to the ice/slush solution, thus infecting the
      patients. There have been no more cases since the freezer was replaced, a
      rigorous cleaning schedule instituted, and steps taken to reduce the possibility
      of any further contamination.

PMID- 16899329
TI  - High uptake of 2,4,6-trinitrotoluene by vetiver grass--potential for
      phytoremediation?
AB  - 2,4,6-Trinitrotoluene (TNT) is a potent mutagen, and a Group C human carcinogen
      that has been widely used to produce munitions and explosives. Vast areas that
      have been previously used as ranges, munition burning, and open detonation sites
      are heavily contaminated with TNT. Conventional remediation activities in such
      sites are expensive and damaging to the ecosystem. Phytoremediation offers a cost
      effective, environment-friendly solution, utilizing plants to extract TNT from
      contaminated soil. We investigated the potential use of vetiver grass (Vetiveria
      zizanioides) to effectively remove TNT from contaminated solutions. Vetiver grass
      plants were grown in hydroponic systems containing 40 mg TNTL(-1) for 8d. Aqueous
      concentrations of TNT reached the method detection limit ( approximately 1 microg
      L(-1)) within the 8-d period, demonstrating high affinity of vetiver for TNT,
      without any visible toxic effects. Results from this preliminary hydroponic study
      are encouraging, but in need of verification using TNT-contaminated soils.

PMID- 16899330
TI  - Meta-analysis of the relative sensitivity of semi-natural vegetation species to
      ozone.
AB  - This study identified 83 species from existing publications suitable for
      inclusion in a database of sensitivity of species to ozone (OZOVEG database). An
      index, the relative sensitivity to ozone, was calculated for each species based
      on changes in biomass in order to test for species traits associated with ozone
      sensitivity. Meta-analysis of the ozone sensitivity data showed a wide inter
      specific range in response to ozone. Some relationships in comparison to plant
      physiological and ecological characteristics were identified. Plants of the
      therophyte lifeform were particularly sensitive to ozone. Species with higher
      mature leaf N concentration were more sensitive to ozone than those with lower
      leaf N concentration. Some relationships between relative sensitivity to ozone
      and Ellenberg habitat requirements were also identified. In contrast, no
      relationships between relative sensitivity to ozone and mature leaf P
      concentration, Grime's CSR strategy, leaf longevity, flowering season, stomatal
      density and maximum altitude were found. The relative sensitivity of species and
      relationships with plant characteristics identified in this study could be used
      to predict sensitivity to ozone of untested species and communities.

PMID- 16899331
TI  - Developing regulations for occupational exposures to health hazards in Malaysia.
AB  - In Malaysia exposures in the workplace are regulated under the Factories and
      Machinery Act (FMA), 1967 and also under the more comprehensive Occupational
      Safety and Health Act (OSHA) enacted in 1994. With OSHA 1994 the philosophy of
      legislating safety and health in the workplace changed from one that was very
      prescriptive and containing detailed technical provisions under FMA, 1967 to one
      that is more flexible and encourages self-regulation under OSHA 1994. OSHA 1994
      is supported by regulations, codes of practices and guidelines to further clarify
      the provisions in the Act. Under the FMA 1967 emphasis was on safety while with
      OSHA 1994 there has been equal emphasis on addressing health hazards in the
      workplace. Regulations for occupational exposures are developed by the Department
      of Occupational Safety and Health with tripartite and stakeholder consultation.
      When developing these regulations International Labor Organization Conventions,
      laws of other countries and occupational exposure standards adopted
      internationally are reviewed. The government also conducts surveys to collect
      information on both exposures and health effects in workplaces to have better
      understanding on specific occupational health problems. Effective law enforcement
      is crucial in ensuring compliance to safety and health law. The challenge at the
      moment is to ensure all employers and employees, particularly those in the small
      and medium enterprises, understand and comply with the provisions stipulated in
      the legislation.

PMID- 16899332
TI  - Long-term safety of alpha-lipoic acid (ALA) consumption: A 2-year study.
AB  - Alpha-lipoic acid (ALA) (CAS RN 1077-28-7), also referred to as thioctic acid,
      has been demonstrated to exhibit strong anti-oxidant properties. In order to test
      the long-term toxicity of ALA, groups of 40-50 male and female, 5-6-week-old,
      Sprague-Dawley rats were subjected to oral administration of 20, 60, or 180 mg/kg
      body weight (bw)/day ALA for 24 months. There was no significant difference
      between control animals and treated animals at 20 or 60 mg/kg bw/day with respect
      to body weight gain, food consumption, behavioural effects, haematological and
      clinical chemistry parameters, and gross and histopathological findings. In all
      treatment groups, mortality was slightly lower as compared to the control. The
      absolute weights of the heart (high-dose males), thymus (high-dose males), and
      left adrenal (mid-dose males), liver (high-dose females), and lungs (high-dose
      females) were decreased in comparison to controls. These changes were of no
      toxicological significance. The only notable finding in rats of both sexes dosed
      at 180 mg/kg bw/day was a reduction in food intake relative to the controls and a
      concomitant decrease in body weight. This decrease in body weight led to
      significant differences between the control and high-dose rats with respect to
      the absolute weights of certain organs. However, no gross or histopathological
      changes were associated with these findings. The no-observed-adverse-effect level
      (NOAEL) is considered to be 60 mg/kg bw/day.

PMID- 16899333
TI  - Right hemispheric dominance in processing of unconscious negative emotion.
AB  - Right hemispheric dominance in unconscious emotional processing has been
      suggested, but remains controversial. This issue was investigated using the
      subliminal affective priming paradigm combined with unilateral visual
      presentation in 40 normal subjects. In either left or right visual fields, angry
      facial expressions, happy facial expressions, or plain gray images were briefly
      presented as negative, positive, and control primes, followed by a mosaic mask.
      Then nonsense target ideographs were presented, and the subjects evaluated their
      partiality toward the targets. When the stimuli were presented in the left, but
      not the right, visual fields, the negative primes reduced the subjects' liking
      for the targets, relative to the case of the positive or control primes. These
      results provided behavioral evidence supporting the hypothesis that the right
      hemisphere is dominant for unconscious negative emotional processing.

PMID- 16899334
TI  - Attentional capture by task-irrelevant fearful faces is revealed by the N2pc
      component.
AB  - We measured the N2pc component as an electrophysiological indicator of
      attentional selection to investigate whether fearful faces can attract attention
      even when they are entirely task-irrelevant and attention is focused on another
      demanding visual monitoring task. Participants had to detect infrequent luminance
      changes of the fixation cross, while ignoring stimulus arrays containing a face
      singleton (a fearful face among neutral faces, or neutral face among fearful
      faces) to the left or right of fixation. On trials without a target luminance
      change, an N2pc was elicited by fearful faces presented next to fixation,
      irrespective of whether they were singletons or not, demonstrating that
      irrelevant fearful faces can bias the spatial distribution of attention. The N2pc
      to fearful faces was attenuated when face arrays were presented simultaneously
      with a target luminance change, suggesting that concurrent target processing
      reduces attentional capture by emotional salient events.

PMID- 16899335
TI  - Anticholinergic drugs in patients with bladder outlet obstruction and lower
      urinary tract symptoms: Where do we stand in 2006?

PMID- 16899336
TI  - Terazosin modifies the content of glycosaminoglycans and the activity of matrix
      metalloproteinase 2 in the rat ventral prostate.
AB  - OBJECTIVES: We have investigated the effects of terazosin on the content of
      glycosaminoglycans (GAGs), the activity of matrix metalloproteinase 2 (MMP-2) and
      MMP-9, and the content of tissue inhibitors of MMP (TIMP) in the ventral prostate
      of Wistar rats. METHODS: Rats were treated with terazosin (0.12, 1.2mg/kg orally
      every second day) for 120 d. GAGs were isolated and purified from ventral
      prostate homogenates by lipid extraction, ethanol precipitation, and extensive
      digestion with pronase and DNAse, separated by electrophoresis, and characterised
      using specific enzymes. The activity of MMP-2 and MMP-9 was estimated using
      gelatin zymography and TIMP-1 and TIMP-2 were measured by enzyme-linked
      immunosorbent assay. RESULTS: Terazosin treatment did not affect the weight of
      the ventral prostate gland. The prostate contains hyaluronic acid, chondroitin
      sulfate (CS), dermatan sulfate (DS), and heparan sulfate (HS), MMP-2, TIMP-1, and
      TIMP-2, but not MMP-9. Terazosin caused a significant increase in the relative
      content of DS and a significant decrease in the relative content of CS and to a
      lesser extent of HS. Terazosin evoked a significant increase in the activity of
      proMMP-2 and MMP-2 but did not affect TIMP. CONCLUSIONS: The differential effect
      of terazosin treatment in GAG molecules of the rat prostate may be beneficial
      because CS is known to induce and DS to inhibit cell proliferation. The effect of
      terazosin on GAGs and MMP-2 may contribute in the molecular mechanisms of
      terazosin-induced apoptosis because HS and CS have a proapoptotic effect, whereas
      DS and MMP-2 are antiapoptotic.

PMID- 16899337
TI  - Selective radiosensitization by nitric oxide in tumor cell lines.
AB  - The radiosensitizing effect of nitric oxide (NO) on mouse and human tumor cells
      with different degrees of malignancy was evaluated. Cells pre-treated with the NO
      donor diethylenetriamine-NO (DETA-NO), were irradiated with gamma rays. Survival
      curves were obtained by clonogenicity and fitted to the linear-quadratic model.
      Results demonstrated an association between radiosensitization and degree of
      malignancy. The more malignant the cell line, the higher the degree of
      radiosensitization by DETA-NO. In conclusion, the differential radiosensitizing
      effect of DETA-NO shown here is of great interest for the potential use of NO in
      radiotherapy, due to an enhanced radiation effect on tumor vs. normal tissue.

PMID- 16899338
TI  - Human error and time of occurrence in hazardous material events in mining and
      manufacturing.
AB  - Human error has played a role in several large-scale hazardous materials events.
      To assess how human error and time of occurrence may have contributed to acute
      chemical releases, data from the Hazardous Substances Emergency Events
      Surveillance (HSEES) system for 1996-2003 were analyzed. Analyses were restricted
      to events in mining or manufacturing where human error was a contributing factor.
      The temporal distribution of releases was also evaluated to determine if the
      night shift impacted releases due to human error. Human error-related events in
      mining and manufacturing resulted in almost four times as many events with
      victims and almost three times as many events with evacuations compared with
      events in these industries where human error was not a contributing factor (10.3%
      versus 2.7% and 11.8% versus 4.5%, respectively). Time of occurrence of events
      attributable to human error in mining and manufacturing showed a widespread
      distribution for number of events, events with victims and evacuations, and
      hospitalizations and deaths, without apparent increased occurrence during the
      night shift. Utilizing human factor engineering in both front-end ergonomic
      design and retrospective incident investigation provides one potential systematic
      approach that may help minimize human error in workplace-related acute chemical
      releases and their resulting injuries.

PMID- 16899339
TI  - In vitro activity of Peltophorum africanum Sond. (Fabaceae) extracts on the egg
      hatching and larval development of the parasitic nematode Trichostrongylus
      colubriformis.
AB  - Trichostrongylus colubriformis is an important cause of parasitic gastroenteritis
      in ruminants, where it causes protracted diarrhoea, rapid loss of weight, loss of
      production and death. The in vitro efficacy of extracts of Peltophorum africanum
      was determined against this parasitic nematode. Eggs and larvae of T.
      colubriformis were incubated at 23 degrees C in the extracts of the leaf, bark
      and root of P. africanum at concentrations of 0.008-25 mg ml-1 for 2 and 5 days,
      respectively. Thiabendazole and water were used as positive and negative
      controls, respectively. Inhibition of egg hatching and larval development
      increased significantly (P<0.05) with increasing concentrations of the extracts.
      Concentrations of 0.2-1.0 mg ml-1 of the extracts of leaf, stem bark, and root
      bark of P. africanum completely inhibited the hatching of eggs and development of
      larvae. No eggs and larvae of T. colubriformis could be observed in wells
      incubated with all the three extracts at concentrations of 5 and 25 mg ml-1. The
      in vitro model results support the traditional use of P. africanum against
      nematode parasites. Further research is required to isolate and structurally
      identify the active anthelmintic compounds, and to improve methods of plant
      extraction of the effective anthelmintic components that will be readily
      adaptable for use by rural communities against helminthosis.

PMID- 16899340
TI  - A study on intestinal helminthes of dogs, foxes and jackals in the western part
      of Iran.
AB  - Human infection especially with helminth parasites is an emerging health issue,
      as the human environment is increasingly shared with infected animals, either
      pets or wild life. In this survey, the intestinal content of 83 stray dogs, 22
      red foxes and 10 golden Jackals collected from the West Azarbaijan, Kordestan and
      Kermanshah provinces in the west of Iran, were studied for the presence of
      helminth parasites. The percentage of different species recovered from these
      animals is listed as follows: From stray dogs: Toxocara canis (6.02%), Toxascaris
      leonina (32.53%), Ancylostoma caninum (3.61%), Oxynema sp. (1.35%), Rictularia
      affinis (12.05%), Taenia hydatigena (53.01%), Taenia ovis (7.23%), Taenia
      multiceps (4.82%), Echinococcus granulosus (13.25%), Dipylidium caninum (38.55%),
      Mesocestoides lineatus (26.50%) and Macracanthorhynchus hirudinaceus (4.82%).
      From red foxes: T. canis (4.54%), T. leonina (31.82%), A. caninum (4.54%),
      Uncinaria stenocephala (13.64%), Oxynema sp. (9.09%), R. affinis (54.54%),
      Strongyloides sp. (4.54%), Physaloptera sp. (4.54%), T. hydatigena (9.09%), E.
      granulosus (4.54%), D. caninum (9.09%), M. lineatus (81.82%), Joyeuxiella
      pasqalei (27.27%), Diplopylidium nolleri (4.54%), M. hirudinaceus (22.72%) and
      Macracanthorhynchus sp. (9.09%). From golden jackals: T. canis (10%), T. leonina
      (30%), R. affinis (50%), T. hydatigena (10%), D. caninum (20%), M. lineatus
      (70%), J. pasqalei (30%.), Alaria canis (10%), M. hirudinaceus (30%) and
      Macracanthomynchus sp. (10%).

PMID- 16899341
TI  - Burns sustained in combat explosions in Operations Iraqi and Enduring Freedom
      (OIF/OEF explosion burns).
AB  - BACKGROUND: Burns comprise 5% of casualties evacuated from Operations Iraqi and
      Enduring Freedom (OIF and OEF). Many OIF/OEF burns result from the enemy's
      detonation of explosives. We reviewed these to evaluate mission impact and
      provide recommendations for improved combat burn protection. Data were compared
      to those from the Vietnam War. METHODS: All OIF/OEF patients with significant
      burns are treated at the U.S. Army Institute of Surgical Research (ISR). A review
      from April 2003 to April 2005 was undertaken. Records were obtained and
      demographics, burn severity and pattern, and early outcomes recorded. RESULTS:
      Two hundred and seventy-four OIF/OEF burn patients were treated, 142 (52%)
      sustained burns in explosions from hostile action. Age was 26+/-7 years (mean+/
      S.D.). Mortality was 4%. The annual rate of combat explosion as a cause for burns
      increased from 18% to 69%, total body surface area burned increased from 15+/-12
      to 21+/-23%, injury severity score rose from 8+/-11 to 17+/-18, and frequency of
      inhalation injury rose from 5% to 26%. Improvised explosive devices caused 55% of
      casualties, car bombs 16%, rocket-propelled grenades 15% and 14% other. The hands
      (80% of patients) and the face (77%) were the most frequently burned body areas.
      Burns were isolated to the hands in 6% of patients and to the face and hands in
      15%. An average of 52+/-30% of the surface area of the hands and 45+/-26% of the
      face was burned. Mean length of stay was 24+/-25 days (median 14). Though 77% of
      patients were discharged without global disability, only 36% returned to full
      military duty. A similar pattern of injury and disposition was seen at the Army
      burn center in Vietnam (1966-1968), but mortality was higher (7.9%). CONCLUSION:
      Burns resulting from combat explosions increased in frequency, size and injury
      severity. Burns were concentrated on areas not protected by clothing or
      equipment. These injuries created long hospital stays and frequently prevented
      soldiers from returning to duty. While wound distribution has not changed, combat
      burn care has improved, and continued emphasis on military protective equipment
      for the hands and face is warranted.

PMID- 16899342
TI  - The P/Q-type voltage-dependent calcium channel as pharmacological target in
      spinocerebellar ataxia type 6: gabapentin and pregabalin may be of therapeutic
      benefit.
AB  - Voltage-dependent calcium channels (VDCCs) are heteromultimeric complexes that
      mediate calcium influx into cells in response to changes in membrane potential.
      The alpha1A subunit, encoded by the CACNA1A gene, is the pore-forming subunit
      specific to the neuronal P/Q-type VDCCs. These are implicated in fast excitatory
      and inhibitory neurotransmission. Their highest levels of expression are found in
      the Purkinje cell layer of the cerebellum, and in the hippocampus.
      Spinocerebellar ataxia type 6 (SCA 6) is an autosomal dominant cerebellar
      degeneration that shares neuropathological findings with late-onset cortical
      cerebellar atrophy (CCA). It is caused by an abnormal expansion of a
      trinucleotide (CAG) repeat in exon 47 of CACNA1A, on chromosome 19p13. This
      translates into a polyglutamine (polyQ) tract of prolonged length in the carboxyl
      terminal of the alpha1A subunit. Heterologous expression of mutated alpha1A
      subunits results in increased channel inactivation in electrophysiological tests.
      No treatment is known to improve SCA 6 at present, as none of the available drugs
      is able to reverse alpha1A dysregulation, nor disturbed protein aggregation,
      transport and localization in this disease. The drugs gabapentin and pregabalin
      interact with the alpha2delta subunit of the P/Q-type VDCCs. Gabapentin and
      pregabalin slow the rate of inactivation in recombinant P/Q-type VDCCs, expressed
      in Xenopus oocytes. These drugs improve ataxia in cases of CCA,
      olivopontocerebellar atrophy and ataxia-telangiectasia. On the basis of the
      neuropathological identity of SCA 6 with CCA, and given the capacity of
      gabapentin and pregabalin to decrease P/Q-type VDCCs inactivation, in this paper
      the authors put forward the hypothesis that the administration of gabapentin and
      pregabalin might prove beneficial in SCA 6 as the ataxia caused by this disease
      would be expected to improve. The authors hope that researchers working with this
      illness will be inspired and encouraged to undertake the appropriate clinical and
      experimental work.

PMID- 16899343
TI  - Cytosine deaminase producing Clostridium may be used in detection of tumors.

PMID- 16899344
TI  - Low levels of B-type natriuretic peptide predict poor clinical outcomes in
      patients with chronic and advanced heart failure.
AB  - B-type natriuretic peptide (BNP) is a neurohormone produced mainly by ventricular
      myocytes in response to increased left ventricular end-diastolic pressure.
      Patients with acute decompensated heart failure often have elevated plasma BNP.
      However, recent clinical observations have demonstrated that in patients with
      advanced heart failure, the plasma level of BNP is lower than those with acute
      heart failure. We hypothesized that a lower circulating BNP level in patients
      with chronic and advanced heart failure is due to the exhaustion of the
      biosynthesis mechanisms and is associated with a poor outcome in these patients.

PMID- 16899345
TI  - Referred muscle pain is primarily peripheral in origin: the "barrier-dam" theory.
AB  - The mechanisms leading to the frequent occurrence of referred muscle pain (RP)
      are largely unknown. It is possible that RP is caused by the increased
      sensitivity of local muscle nociceptors and/or by a central sensitisation. When
      deep pressure by palpation is used on a subject with smooth fibrotic lesions
      (myofibrosis) in a muscle, RP can originate as a hyperalgesic cutaneous area,
      adjacent to, or totally apart from the pressure pain locus. It is currently
      postulated that a chain reaction is activated implicating triggering of an ever
      increasing number of afferent neurons and facilitation of the synaptic connection
      at the level of the spinal cord, causing more distally a distributed RP via
      convergent efferent pathways. The human interpretation of this phenomenon can be
      misleading when the tested person positions, after a few seconds, his RP distally
      from the site of pressure to the distally located RP area. As a result of what we
      have found in our experimentally induced RP probes, we hypothesize that deep
      pressure on a myofibrosis will, in the first place, within a few seconds,
      increase the nociceptive excitability of the afferent sensitive nerves from the
      RP area to the local spot of pressure on the muscle, which in return will, in the
      second place, excite the whole dependent RP area. The mechanism for referred
      muscle pain proposed in this article is linked to the "pre-local hyper
      excitability theory" or "barrier-dam theory". The afferent sensitive peripheral
      nerves might be entrapped in local muscle hardenings (barrier-dam) with the
      consequence of the hyper-excitation of pre-local nerves between the distally
      referred pain area and the local muscular zone of tenderness. The primary
      pathogenesis of referred muscle pain is likely to be a peripheral sensitization
      with additionally a central modulation and not vice versa. Clinical and
      fundamental studies with experimentally induced RP are nevertheless needed to
      examine the hypothesis.

PMID- 16899346
TI  - Development and evaluation of a diagnostic PCR for Mycoplasma synoviae using
      primers located in the intergenic spacer region and the 23S rRNA gene.
AB  - Mycoplasma synoviae (Ms) is an important pathogen of poultry, causing economic
      losses to this industry. Early and reliable diagnosis is a key to controlling the
      spread of this organism. In this study, a polymerase chain reaction with one
      primer based on the intergenic spacer region (ISR) was validated for detection of
      Ms. The ISR primer was paired with a general primer from within the 23S rRNA
      gene. The PCR primers were tested with the 22 other recognised avian Mycoplasma
      species to check the specificity and with 21 field isolates of Ms from various
      hosts and countries, and with several swab samples. The PCR appeared to be
      specific and sensitive. Four different sample preparation methods were compared
      for use in this PCR, and the amplification protocol was compared with three
      others, confirming the comparative sensitivity of the new PCR.

PMID- 16899347
TI  - Analysis of body fluid mixtures by mtDNA sequencing: An inter-laboratory study of
      the GEP-ISFG working group.
AB  - The mitochondrial DNA (mtDNA) working group of the GEP-ISFG (Spanish and
      Portuguese Group of the International Society for Forensic Genetics) carried out
      an inter-laboratory exercise consisting of the analysis of mtDNA sequencing
      patterns in mixed stains (saliva/semen and blood/semen). Mixtures were prepared
      with saliva or blood from a female donor and three different semen dilutions
      (pure, 1:10 and 1:20) in order to simulate forensic casework. All labs extracted
      the DNA by preferential lysis and amplified and sequenced the first mtDNA
      hypervariable region (HVS-I). Autosomal and Y-STR markers were also analysed in
      order to compare nuclear and mitochondrial results from the same DNA extracts. A
      mixed stain prepared using semen from a vasectomized individual was also
      analysed. The results were reasonably consistent among labs for the first
      fractions but not for the second ones, for which some laboratories reported
      contamination problems. In the first fractions, both the female and male
      haplotypes were generally detected in those samples prepared with undiluted
      semen. In contrast, most of the mixtures prepared with diluted semen only yielded
      the female haplotype, suggesting that the mtDNA copy number per cell is smaller
      in semen than in saliva or blood. Although the detection level of the male
      component decreased in accordance with the degree of semen dilution, it was found
      that the loss of signal was not consistently uniform throughout each
      electropherogram. Moreover, differences between mixtures prepared from different
      donors and different body fluids were also observed. We conclude that the
      particular characteristics of each mixed stain can deeply influence the
      interpretation of the mtDNA evidence in forensic mixtures (leading in some cases
      to false exclusions). In this sense, the implementation of preliminary tests with
      the aim of identifying the fluids involved in the mixture is an essential tool.
      In addition, in order to prevent incorrect conclusions in the interpretation of
      electropherograms we strongly recommend: (i) the use of additional sequencing
      primers to confirm the sequencing results and (ii) interpreting the results to
      the light of the phylogenetic perspective.

PMID- 16899348
TI  - Successful treatment of eosinophilic otitis media using ramatroban: report of two
      cases.
AB  - OBJECTIVE: The pathogenesis of eosinophilic otitis media is not yet fully
      understood. The purpose of this paper is to describe the clinical course of our
      two patients with eosinophilic otitis media and to discuss the pathogenesis and
      treatment of this intractable condition. METHODS: Two cases of eosinophilic
      otitis media were treated with ramatroban. RESULTS: The middle ear effusion has
      been well controlled in both patients for more than 1 year with minimal
      corticosteroid therapy. CONCLUSIONS: Our experience suggests that the
      pathogenesis of eosinophilic otitis media is related to the pharmaceutical
      effects of ramatroban, i.e., inhibition of the thromboxane A2 receptor (TP) and
      the chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2).

PMID- 16899349
TI  - Evolutionary diversity of ketoacyl synthases in cellulolytic myxobacterium
      Sorangium.
AB  - The diversity of type I polyketide synthases (PKSs) in cellulolytic myxobacterium
      Sorangium was explored by assaying the ketoacyl synthases (KSs) in 10 Sorangium
      strains with two degenerate primer sets and 64 different KS fragments were
      obtained. For their deduced amino acid sequences, eight were identical to three
      known KSs from Sorangium and Magnetospirillum, while the others showed 54-83%
      identities to the modular KS domains reported from various microorganisms. Parts
      of the Sorangium KSs tightly share the clade with Actinobacteria excluding any
      other analyzed myxobacterial KSs, or with Cyanobacteria /Myxobacteria. Parts are
      widely located in the three functional groups - "Loading", "NRPS/PKS" and "Trans
      AT". Sorangium KSs in the Actinobacteria, Cyanobacteria/Myxobacteria, or
      "Loading" clade further evolved independently on its own genus. Notably, the
      modular KSs from other Myxobacteria genera, i.e. Myxococcus, Stigmatella,
      Melittangium, Cystobacter and Angiococcus are often distributed crosswise and
      form non-Sorangium blend subgroups. "NRPS/PKS" and "Trans-AT" are two rather
      diverse groups and the Sorangium KSs in these clades evolved crosswise with other
      taxa lineages. The results presented in this paper suggest that the inherent
      genetic strategies, together with frequent gene importing from many organisms
      (HGT) have contributed to the evolution of modular PKSs in Sorangium. These
      findings reinforce that Sorangium strains are really excellent creators for novel
      and diverse polyketides.

PMID- 16899350
TI  - Interactive effects of fumonisin B1 and alpha-zearalenol on proliferation and
      cytokine expression in Jurkat T cells.
AB  - Mycotoxins are secondary metabolites of fungi that grow on various food and feed.
      These compounds elicit a wide spectrum of toxicological effects, including the
      capacity to alter normal immune function. Feed commodities are usually
      contaminated with more than one mycotoxin; however, extensive information on the
      interaction between concomitantly occurring mycotoxins and the consequence for
      their toxicity is lacking. In the present study, we examined the effects in vitro
      of fumonisin B1 (FB1) and alpha-zearalenol (alpha-ZEA), alone or in combination,
      on the immune function in the human lymphoblastoid Jurkat T cell line. Treatment
      of cells with increasing concentrations of FB1 resulted in a dose-dependent
      induction of proliferation. In contrast, alpha-ZEA showed a marked inhibitory
      effect on cell proliferation, even at very low doses, essentially mediated by
      apoptosis. In stimulated cells pre-incubated with FB1, the levels of IL-2 and IFN
      gamma mRNAs were similar to control whereas a reduction of cytokine transcripts
      was reported following alpha-ZEA treatment. Interestingly, co-administration of
      mycotoxins resulted in further inhibition of both proliferation and IFN gamma
      mRNA expression when compared with alpha-ZEA alone. In conclusion, FB1 and alpha
      ZEA showed different immunomodulation abilities when individually administered.
      Combination of mycotoxins resulted instead in interactive effects.

PMID- 16899351
TI  - Fast computation of a gated dipole field.
AB  - We address the need to develop efficient algorithms for numerical simulation of
      models, based in part or entirely on adaptive resonance theory. We introduce
      modifications that speed up the computation of the gated dipole field (GDF) in
      the Exact ART neural network. The speed increase of our solution amounts to at
      least an order of magnitude for fields with more than 100 gated dipoles. We adopt
      a 'divide and rule' approach towards the original GDF differential equations by
      grouping them into three categories, and modify each category in a separate way.
      We decouple the slow-dynamics part - the neurotransmitters from the rest of
      system, solve their equations analytically, and adapt the solution to the
      remaining fast-dynamics processes. Part of the node activations are integrated by
      an unsophisticated numerical procedure switched on and off according to rules.
      The remaining activations are calculated at equilibrium. We implement this logic
      in a Generalized Net (GN) - a tool for parallel processes simulation which
      enables a fresh look at developing efficient models. Our software implementation
      of generalized nets appears to add little computational overhead.

PMID- 16899352
TI  - Analysis of coding-polymorphisms in NOTCH-related genes reveals NUMBL poly
      glutamine repeat to be associated with schizophrenia in Brazilian and Danish
      subjects.
AB  - Abnormality in neurodevelopment is one of the most robust hypotheses on the
      etiology of schizophrenia and has found substantial support from brain imaging
      and genetic studies. Neurodevelopmental processes involve several signaling
      pathways, including the Notch, but little is known at present regarding their
      possible involvement in schizophrenia. In the present study we investigated the
      link of non-synonymous variants of five genes of the Notch pathway (NOTCH2,
      NOTCH3, JAGGED2, ASCL1 and NUMBL) to schizophrenia in a group of 200 Brazilian
      patients and 200-paired controls. Also, we replicated the association of the
      NUMBL variant, our most promising finding, in an unrelated set of 684 Danish
      patients and controls. When the Brazilian and Danish cohorts were merged, a total
      of 1084 subjects, we found the allele 18 CAG of NUMBL (p=0.003, x2=8.88, OR=1.30,
      95% CI 1.09-1.56) as well as the 18/18 CAG genotype (p=0.002, x2=9.46, OR=1.46,
      95% CI 1.15-1.87) to be associated with schizophrenia. The consistency of this
      finding in two independent and unrelated populations reinforces the veracity of
      this association.

PMID- 16899353
TI  - Ciprofloxacin/metronidazole versus beta-lactam-based treatment of intra-abdominal
      infections: a meta-analysis of comparative trials.
AB  - Intra-abdominal infections are polymicrobial and result in substantial morbidity
      and mortality. The combination of ciprofloxacin/metronidazole as well as several
      beta-lactam-based regimens are among the commonly used regimens for the treatment
      of patients with such infections. Thus, we sought to review the evidence from
      available comparative clinical trials studying ciprofloxacin/metronidazole versus
      broad-spectrum beta-lactam-based regimens in the treatment of intra-abdominal
      infections. Studies for the meta-analysis were retrieved from searches of the
      PubMed database. Five available comparative trials (four randomised controlled
      trials and one non-randomised comparative trial) including 1431 patients with
      intra-abdominal infections were included in the meta-analysis. There was a
      statistically significant difference between the compared arms with regard to
      cure in favour of the ciprofloxacin/metronidazole combination (odds ratio
      (OR)=1.69, 95% confidence interval (CI) 1.20-2.39). There was no statistically
      significant difference between the compared arms with regard to total mortality
      (OR=1.10, 95% CI 0.71-1.69), mortality attributable to infection (OR=1.42, 95% CI
      0.66-3.06) and toxicity (OR=1.25, 95% CI 0.66-2.35). In conclusion, pooled data
      from the available comparative trials suggest that the
      ciprofloxacin/metronidazole combination may be superior to beta-lactam-based
      therapeutic regimens in the treatment of intra-abdominal infections with regard
      to cure of infections, although no difference in mortality was found.

PMID- 16899354
TI  - Genetics and personality traits in patients with social anxiety disorder: a case
      control study in South Africa.
AB  - BACKGROUND: Social anxiety disorder (SAD) is among the most common of all
      psychiatric disorders with lifetime prevalence estimates ranging from 7% to 13%.
      Although there is evidence that SAD has a strong familial basis, there are few
      studies of potential candidate genes. In addition to a genetic association, there
      is also the possibility that temperamental risk factors for the disorder may be
      genetically transmitted. Against this background, our aims were threefold: i.) to
      compare patients and controls with respect to personality traits, ii.) to
      genotype a subgroup of these participants to investigate the role of genes
      encoding components of serotonergic (5-HT) and dopaminergic (DA) pathways in
      patients with SAD and iii.) to compare differences in temperament dimensions
      between carriers of different (dominant vs. recessive) alleles for selected
      polymorphisms in SAD patients. METHODS: Sixty-three patients (n=63; 35 male, 28
      female) with a DSM-IV diagnosis of generalized SAD and SPIN-scores >18, and age
      matched control participants (n=150; 31 male, 119 female) were included in the
      study. The Temperament and Character Inventory (TCI) was used to measure
      behaviours associated with specific personality dimensions (i.e.
      temperament/character). DNA was extracted and genotyped to investigate the role
      of select candidate genes encoding components in serotonergic and dopaminergic
      pathways in mediating the development of SAD. To achieve this, the frequency of
      variants in 5-HT and DA genes was compared between a Caucasian subset of SAD
      patients (n=41) and a convenience sample of Caucasian controls (n=88), using case
      control association analyses. We also investigated the frequency of variants in 5
      HT and DA-related genes across temperament characteristics in SAD patients, using
      analyses of variance (ANOVA). RESULTS: Patients scored significantly higher on
      harm avoidance (p<0.001) but lower on novelty seeking (p=0.04) and self
      directedness (p=0.004) compared to controls. In the Caucasian subset, there was a
      difference between patients and controls in distribution of the 5-HT(2A)T102C
      polymorphism, with significantly more patients harboring T-containing genotypes
      (T-containing genotypes: [T/T+T/C] vs. [C/C]) (chi2=7.55; p=0.012). Temperament
      dimensions did not, however, differ significantly between carriers of different
      (dominant vs. recessive) alleles for the 5-HT(2A)T102C polymorphism in SAD
      patients. CONCLUSIONS: The results suggest a possible role for the 5-HT(2A)T102C
      polymorphism in the development of SAD. To date genetic findings in SAD have been
      inconsistent; nevertheless, serotonergic variants, and their associations with
      temperaments (e.g. reward dependence) deserve further exploration, in the hope
      that endophenotypes relevant to SAD can ultimately be delineated.

PMID- 16899355
TI  - Nanoencapsulation of usnic acid: An attempt to improve antitumour activity and
      reduce hepatotoxicity.
AB  - Despite the recognised antiproliferative and antitumour properties of usnic acid,
      its therapeutic application has yet to be introduced. In fact, the high
      hepatotoxicity and low water solubility of usnic acid have somewhat restricted
      its practical use in anticancer therapy. The aim of this study was therefore to
      investigate the antitumour activity of usnic acid encapsulated into nanocapsules
      prepared with lactic co-glycolic acid polymer. Usnic acid-loaded nanocapsules
      were obtained using the interfacial deposition of a preformed polymer. The
      antitumour activity was confirmed on an ascitic tumour (Sarcoma-180) implanted in
      Swiss mice and estimated by means of the tumour inhibition. The results of
      antitumour activity confirmed that the encapsulation of usnic acid into PLGA
      nanocapsules produced a 26.4% increase in tumour inhibition as compared with the
      standard free usnic acid treatment. Vacuolization of hepatocytes and a mild
      lymphocytic infiltration in portal spaces were observed in animals treated with
      free usnic acid. However, this hepatotoxicity was substantially reduced when
      animals were treated with usnic acid-loaded nanocapsules. No histological changes
      were noticed in the kidneys or spleen of animals treated either with usnic acid
      or usnic acid-loaded nanocapsules. These results suggest that nanoencapsulation
      may be a way of enabling usnic acid to be used in chemotherapy.

PMID- 16899356
TI  - The antitumor and antioxidative activities of polysaccharides isolated from
      Isaria farinosa B05.
AB  - The water-soluble intra-polysaccharides WIPS1 and water-soluble extra
      polysaccharides WEPS1 were isolated from Isaria farinosa B05 through ethanol
      precipitation and gel permeation chromatography (GPC). Their characteristics were
      determined by chemical analysis, gas chromatography, GPC and IR spectroscopy. The
      results show that WIPS1 contained 90.3% carbohydrate, 8.00% uronic acid, 7.15%
      protein and three kinds of monosaccharides including mannose, galactose and
      glucose with a molar ratio of 8.0:4.8:1.0. WEPS1 contained 93.4% carbohydrate,
      8.06% uronic acid, 4.40% protein and three kinds of monosaccharides including
      mannose, galactose and glucose with a molar ratio of 21.6:4.7:1.0. WIPS1 and
      WEPS1 had a molecular weight of 42 and 208kDa, respectively. The in vivo tests in
      mice indicate that WIPS1 and WEPS1 had significant antitumor and antioxidative
      activities to some extent.

PMID- 16899357
TI  - Psychological aspects in the perception of dyspnea in obstructive pulmonary
      diseases.
AB  - Dyspnea is an impairing symptom in obstructive pulmonary diseases. Besides
      multiple physiological pathways contributing to this sensation recent research
      has demonstrated an important role of psychological factors in the perception of
      dyspnea. The present review article synthesizes the research literature with
      regard to psychological aspects of the perception of dyspnea as well as other
      dyspnea-related issues such as course of disease, neuropsychological correlates
      and interventions that focus on psychological or behavioural changes. The
      available data show that inaccurate perception of dyspnea is related to poorer
      treatment outcome in obstructive pulmonary diseases and is impacted upon by
      emotional, attentional and learning processes. Neuropsychological deficits might
      further contribute to this association. Different psychological and behavioural
      interventions might reduce comorbid psychological disorders and thus improve the
      perception of dyspnea. However, future research is clearly required to
      substantiate current findings.

PMID- 16899358
TI  - Distance and oxygen desaturation in 6-min walk test predict prognosis in COPD
      patients.
AB  - The aim of the present study was to predict the prognosis of Chronic obstructive
      pulmonary disease (COPD) patients who underwent comprehensive pulmonary
      rehabilitation (PR). A total of 144 patients who performed PR between 1992 and
      1999 was assessed. After PR, 67 patients underwent lung volume reduction surgery
      (LVRS). Baseline data before PR consisted of body mass index, serum albumin
      levels, use of supplement oxygen at home, pulmonary function, arterial blood gas
      analysis, and distance and fall of hemoglobin oxygen saturation (DeltaSpO(2)) in
      6-min walk test. In addition to pre-PR factors, treatment with LVRS was taken
      into the analysis. The prognostic significance of variables influencing survival
      was determined by univariate analysis with Log rank test or multivariate analysis
      using Cox's proportional hazard model. By a median follow-up time of 8.4 years,
      the median survival time was 8.1 years (95% confidence interval: 6.9-9.4 years).
      Albumin level, PaCO(2), distance and DeltaSpO(2) were significant prognostic
      factors in univariate analysis. LVRS did not affect the prognosis. The
      multivariate analysis showed short distance and increase of DeltaSpO(2) as
      significant independent predictors of the risk of death. 6-min walk test was very
      useful for predicting the prognosis of the COPD patients.

PMID- 16899359
TI  - Mechanically mediated electron transfer in model metallo-enzyme interfaces.
AB  - In this paper, we develop a physical analysis of charge transfer in the model
      'metallo-enzyme' complex which consists of a synthetic redox-addressed assembly
      (a 'reaction center') hybridized with a quantum dot (a gold nanoparticle) and
      attached via molecular bridge (a spacer) to the electrode. This artificial system
      allows us to model electronic transduction in experimental redox ezyme-gold
      nanoparticle hybrid structure recently reported by Xiao et al. [Xiao, Y.,
      Patolsky, F., Katz, E., Hainfeid, J.F., Willner, I., 2003. Science 299, 1877
      1881]. We consider a photosensitive spacer that allows us to control the
      conductivity of the bridge by light. In this paper we will focus on a special
      type of nanoelectro-mechanical processes in this system and investigate single
      electronic effects in there.

PMID- 16899360
TI  - Understanding cellular networks to improve hematopoietic stem cell expansion
      cultures.
AB  - Efforts to develop culture technologies capable of eliciting robust human blood
      stem cell growth have met with limited success. Considering that adult stem cell
      cultures are complex systems, comprising multiple cell types with dynamically
      changing intracellular signalling environments and cellular compositions, this is
      not surprising. Typically treated as single-input single-output systems, adult
      stem cell cultures are better described as complex, non-linear, multiple-input
      multiple-output systems wherein the proliferation of subpopulations of cells
      leads to the formation of intercellular endogenously secreted protein interaction
      networks. Genomic and proteomic tools need to be applied to generate high
      throughput (and ideally high-content) biological measurements of stem cell
      culture evolution. Datasets describing cellular interaction networks need to be
      integrated into predictive models of in vitro stem cell development. Ultimately,
      such models will serve as a starting point for the rational design of blood stem
      cell expansion bioprocesses utilizing dynamic system perturbations to achieve the
      preferential expansion of target cell populations.

PMID- 16899361
TI  - Quantitative in vivo microscopy: the return from the 'omics'.
AB  - The confluence of recent advances in microscopy instrumentation and image
      analysis, coupled with the widespread use of GFP-like proteins as reporters of
      gene expression, has opened the door to high-throughput in vivo studies that can
      provide the morphological and temporal context to the biochemical pathways
      regulating cell function. We are now able to quantify the concentration and three
      dimensional distribution of multiple spectrally resolved GFP-tagged proteins.
      Using automatic segmentation and tracking we can then measure the dynamics of the
      processes in which these elements are involved. In this way, parallel studies are
      feasible where multiple cell colonies treated with drugs or gene expression
      repressors can be monitored and analyzed to study the dynamics of relevant
      biological processes.

PMID- 16899363
TI  - Patient-reported assessment of quality care at end of life: development and
      validation of Quality Care Questionnaire-End of Life (QCQ-EOL).
AB  - Our goal was to validate an instrument with which terminally ill patients could
      evaluate the quality of care they receive at the end of life (EOL). Questionnaire
      development followed a four-phase process: item generation and reduction,
      construction, pilot testing, and field-testing. Using relevance and priority
      criteria and pilot testing, we developed a 16-item questionnaire. Factor analyses
      of data from 235 patients resulted in the Quality Care Questionnaire-End of Life
      (QCQ-EOL) covering dignity-conserving care, care by health care professionals,
      individualised care, and family relationships. All subscales and total scores
      showed high internal consistency (Cronbach alpha range, 0.73-0.89). The ability
      of total score and selective subscale scores clearly differentiated patients on
      the basis of clinical situation, sense of dignity, and general rating of care
      quality. Correlations of scores between patients and caregivers were substantial.
      The QCQ-EOL can be adopted to assess the quality of care received by terminally
      ill patients.

PMID- 16899362
TI  - Toxicity profile of the immunomodulatory thalidomide analogue, lenalidomide:
      phase I clinical trial of three dosing schedules in patients with solid
      malignancies.
AB  - Thalidomide is an anti-angiogenic agent currently used to treat patients with
      malignant cachexia or multiple myeloma. Lenalidomide (CC-5013) is an
      immunomodulatory thalidomide analogue licensed in the United States of America
      (USA) for the treatment of a subtype of myelodysplastic syndrome. This two
      centre, open-label phase I study evaluated dose-limiting toxicities in 55
      patients with malignant solid tumours refractory to standard chemotherapies.
      Lenalidomide capsules were consumed once daily for 12 weeks according to one of
      the following three schedules: (I) 25 mg daily for the first 7 d, the daily dose
      increased by 25 mg each week up to a maximum daily dose of 150 mg; (II) 25mg
      daily for 21 d followed by a 7-d rest period, the 4-week cycle repeated for 3
      cycles; (III) 10 mg daily continuously. Twenty-six patients completed the study
      period. Two patients experienced a grade 3 hypersensitivity rash. Four patients
      in cohort I and 4 patients in cohort II suffered grade 3 or 4 neutropaenia. In 2
      patients with predisposing medical factors, grade 3 cardiac dysrhythmia was
      recorded. Grade 1 neurotoxicity was detected in 6 patients. One complete and two
      partial radiological responses were measured by computed tomography scanning; 8
      patients had stable disease after 12 weeks of treatment. Fifteen patients
      remained on treatment as named patients; 1 with metastatic melanoma remains in
      clinical remission 3.5 years from trial entry. This study indicates the
      tolerability and potential clinical efficacy of lenalidomide in patients with
      advanced solid tumours who have previously received multi-modality treatment.
      Depending on the extent of myelosuppressive pre-treatment, dose schedules (II) or
      (III) are advocated for large-scale trials of long-term administration.

PMID- 16899365
TI  - Safety and pharmacokinetics of temozolomide using a dose-escalation, metronomic
      schedule in recurrent paediatric brain tumours.
AB  - The aims of this study were to determine the maximum tolerated dose (MTD),
      toxicity and pharmacokinetics of oral temozolomide administered over 42 d in
      children with recurrent/refractory brain tumours. Cohorts of 3-6 patients were
      treated for 42 d, followed by a 7-d rest period for a maximum of 6 cycles.
      Patients were stratified as heavily pre-treated (HPT) and non-heavily pre-treated
      (NHPT). Starting doses were 50 mg/m2 (HPT) or 75 mg/m2 (NHPT). Out of 28 patients
      enrolled, 20 were evaluable for toxicity and 19 for pharmacokinetics. Three
      patients in the NHPT group developed grade 3/4 haematological toxicity, 2
      experienced dose-limiting toxicity (thrombocytopenia) at 100 mg/m2, and 9/20
      developed grade 3 lymphopenia. MTD in both strata was 85 mg/m2. Responses were
      observed in 4 patients: 2 complete responses (CR) in medulloblastoma and
      supratentorial primitive neuroectodermal tumours (PNET), and 2 partial responses
      (PR) in high-grade glioma, respectively. Overall cumulative exposure was at least
      1.5 times higher than in the 5-d administration schedule. In conclusion, the
      recommended dose of temozolomide is 85 mg/m2 x 42 d. Dose-limiting toxicities are
      thrombocytopenia and lymphopenia. The observed response rate warrants phase II
      studies.

PMID- 16899364
TI  - Role of prostaglandin E2 in the invasiveness, growth and protection of cancer
      cells in malignant pleuritis.
AB  - The recurrence of pleural effusions is a common event in a variety of neoplastic
      diseases. The objective of this study was to identify the mechanisms promoting
      the homing and growth of cancer cells within the pleural space. A cancer cell
      line recovered from malignant pleural fluids (lung adenocarcinoma cell line) that
      constitutively expresses cyclooxygenase 2 (COX-2) and all types of prostaglandin
      receptors was studied. It was first demonstrated using a matrigel system, that
      malignant pleural fluids increase the invasiveness of adenocarcinoma cells more
      than congestive heart failure (CHF) pleural fluids. Moreover, exposure to
      exudative malignant, but not to CHF pleural fluids, increased the mRNA (measured
      by real-time polymerase chain reaction (PCR)) and protein expression of COX-2
      (measured by Western blot), as well as the activation and nuclear translocation
      of nuclear factor kappaB (NFkappaB) in cancer cells. These events are all
      actively regulated by prostaglandin E2 (PGE2), since the addition of synthetic
      PGE2 to cancer cells and the depletion of PGE2 from malignant pleural fluids or
      the inhibition of COX-2 activity significantly increased and reduced these
      phenomena, respectively. Moreover, malignant pleural effusions and synthetic PGE2
      increased the long-term proliferation of cancer cells and reverted the impairment
      in long-term proliferation due to talc exposure. This study demonstrates that
      PGE2 present in malignant effusions contributes to cancer expansion and may
      protect cancer cells by anti-proliferative effects induced by talc.

PMID- 16899366
TI  - Synthesis and biological evaluation of heterocycle containing adamantane 11beta
      HSD1 inhibitors.
AB  - A series of metabolically stable adamantane amide 11beta-HSD1 inhibitors have
      been synthesized and biologically evaluated. These compounds exhibit excellent
      HSD1 potency and HSD2 selectivity and good pharmacokinetic and pharmacodynamic
      profiles.

PMID- 16899367
TI  - Learning from critical case reviews: emergent themes and their impact on
      practice.
AB  - This paper describes the process of conducting critical case reviews as part of a
      leadership programme for critical care. Forty-five cases were reviewed over 2
      years in five different hospitals and permission was sought from local research
      ethics committees and research and development committees for the discussions to
      be treated as research data. Typically the cases presented were patients with
      complex needs whose trajectory of care had not gone smoothly. Key themes to
      emerge from the case reviews were: The case reviews themselves were:
      Communication failures between professional groups, between professional
      themselves, between staff and families, between wards and departments and between
      different hospitals. Documentation was also often less than satisfactory. Teams
      often had problems in working together as a team and different professionals
      often had different expectations of other members of the team. Individual action
      may compensate for weaknesses in formal clinical risk system. The case reviews
      themselves were showcases of the difficulties the health service faces every day
      and the challenges of communicating effectively. The case reviews provided an
      effective medium to both resolve those difficulties and model a means through
      which teams could effectively manage and communicate patient care issues.
      Furthermore their strength as a learning tool was attributed to team learning as
      a powerful catalyst for change.

PMID- 16899368
TI  - Functional somatic symptoms in accident and emergency--An exploratory study.
AB  - OBJECTIVES: To identify the extent and nature of functional somatic symptoms
      (FSS) in a UK Accident and Emergency (A&E) Department. METHODS: A mixed method
      design was used. Data on the number and outcomes of attendances of patients who
      had attended A&E four or more times in a 6-month period, and who had not received
      a medical diagnosis were collected. Levels of anxiety and depression were
      explored and patients were invited to attend an interview with a clinical
      psychologist. RESULTS: One hundred frequent attendees made 595 visits to A&E in 6
      months, with 20% of visits resulting in a hospital admission. Participants
      revealed high levels of health anxiety, with over half of participants reporting
      a perceived link between psychological factors and their experience of symptoms.
      Over 80% of participants attending the interview wanted further help to manage
      their symptoms and health care utilisation. CONCLUSIONS: Functional somatic
      symptoms are highly distressing for patients and place high demands on health
      care resources. An alternative care pathway to assess and manage FSS in A&E may
      need to be developed to help patients to manage their health anxiety.

PMID- 16899369
TI  - Synthesis of bicyclic molecular scaffolds (BTAa): an investigation towards new
      selective MMP-12 inhibitors.
AB  - Starting from 3-aza-6,8-dioxa-bicyclo[3.2.1]octane scaffold (BTAa) a virtual
      library of molecules was generated and screened in silico against the crystal
      structure of the Human Macrophage Metalloelastase (MMP-12). The molecules
      obtaining high score were synthesized and the affinity for the catalytic domain
      of MMP-12 was experimentally proved by NMR experiments. A BTAa scaffold 20 having
      a N-hydroxyurea group in position 3 and a p-phenylbenzylcarboxy amide in position
      7 showed a fair inhibition potency (IC50 = 149 microM) for MMP-12 and some
      selectivity towards five different MMPs. These results, taken together with the X
      ray structure of the adduct between MMP-12, the inhibitor 20 and the
      acetohydroxamic acid (AHA), suggest that bicyclic scaffold derivatives may be
      exploited for the design of new selective matrix metalloproteinase inhibitors
      (MMPIs).

PMID- 16899370
TI  - Elevated plasma triglyceride levels precede amyloid deposition in Alzheimer's
      disease mouse models with abundant A beta in plasma.
AB  - Dietary or pharmacological manipulation of plasma lipids markedly influences
      amyloid deposition in animal models of Alzheimer's Disease (AD). However, it is
      not known whether baseline plasma lipids in AD models differ from wild-type
      littermates throughout the natural history of disease. To address this question,
      we measured plasma total cholesterol and triglyceride levels over time in three
      transgenic AD mouse models in the absence of dietary or pharmacological
      treatments. Total cholesterol levels were not significantly different between
      transgenic and wild-type mice during the development of AD neuropathology in all
      models tested. In contrast, elevated very-low-density lipoprotein (VLDL)
      triglyceride levels preceded amyloid deposition in two AD models with abundant
      plasma A beta. Elevated triglycerides were not accompanied by increased
      inflammatory markers nor decreased lipase activity, but were associated with a
      significant 30% increase in VLDL-triglyceride secretion rate. Our results suggest
      that the presence of A beta in plasma may affect peripheral lipid metabolism
      early in AD pathogenesis.

PMID- 16899371
TI  - 4-1BB-mediated amelioration of experimental autoimmune uveoretinitis is caused by
      indoleamine 2,3-dioxygenase-dependent mechanisms.
AB  - Interphotoreceptor retinoid binding protein (IRBP)-induced experimental
      autoimmune uveoretinitis (EAU) is a CD4+ T cell-mediated autoimmune disease.
      Development of EAU is inhibited by treatment with an agonistic anti-4-1BB mAb.
      Even established EAU was alleviated by anti-4-1BB mAb. However, inhibition of 4
      1BB/4-1BB ligand (4-1BBL) interaction does not suppress the development of EAU.
      It appears that cross-linking of 4-1BB evokes an active antigen-specific
      suppression mechanism rather than merely blocking 4-1BB/4-1BBL interaction. We
      found that administration of anti-4-1BB mAb induced massive clonal expansion of
      CD11c+CD8+ T cells that produced IFN-gamma, resulting in accumulation of a high
      level of indoleamine 2,3-dioxygenase (IDO) in CD11c+ dendritic cells. 4-1BB
      mediated suppression of EAU was reversed by the pharmacological IDO inhibitor, 1
      methyl-tryptophan (1-MT). These studies demonstrate that suppression of EAU
      results from antigen-driven, 4-1BB-mediated expansion of novel CD11c+CD8+ T cells
      that suppress antigen-specific CD4+ T cells via an IDO-dependent mechanism.

PMID- 16899372
TI  - Crocetin prevents AGEs-induced vascular endothelial cell apoptosis.
AB  - Advanced glycation end products (AGEs) are causally correlated with diabetic
      vascular complications. AGEs triggered oxidative reaction then accelerated
      endothelial cell apoptosis is a critical event in the process of vascular
      complications. Crocetin, a carotenoid has been previously shown to have strong
      antioxidant activates. Therefore, this study was designed to investigate the role
      of crocetin on the prevention of AGEs-mediated cell apoptosis in bovine aortic
      endothelial cells (BEC) and the mechanisms involved. Exposure of BEC to 200
      microg/ml AGEs for 48 h results in a significant increase in apoptotic rate,
      compared with control. AGEs-induced DNA fragmentation preferentially occurred in
      the S phase cells. Crocetin prevented AGEs-induced BEC apoptosis, which
      correlates with crocetin attenuation of AGEs mediated increase of intracellular
      reactive oxygen species (ROS) formation and elevation of intracellular Ca2+
      concentration ([Ca2+]i) level (P<0.01 versus AGEs group). These results
      demonstrate that crocetin prevents AGEs-induced BEC apoptosis through ROS
      inhibition and [Ca2+]i stabilization and suggest that crocetin may exert a
      beneficial effect in preventing diabetes-associated vascular complications.

PMID- 16899374
TI  - Experimental investigation of the elastic-plastic deformation of mineralized
      lobster cuticle by digital image correlation.
AB  - This study presents a novel experimental approach to the characterization of the
      deformation of a mineralized biological composite using arthropod cuticle as a
      model material. By performing tensile tests combined with a detailed strain
      analysis via digital image correlation, the elastic-plastic deformation behavior
      of the endocuticle of the American lobster Homarus americanus is examined. The
      test specimens originate from the pincher and crusher claws. For evaluating the
      effect of moisture on the deformation behavior, the samples are tested both in
      dry and in wet state. Sample characterization using the digital image correlation
      method requires a stochastic spot pattern on the sample surface. Digital images
      are then taken at subsequent deformation stages during the mechanical test. These
      images are used to calculate the displacement, the displacement gradient, and the
      strain fields via pattern correlation. The method is applied both, at a global
      scale to measure with high precision the stress-strain behavior of the bulk
      cuticle and at a microscopic scale to reveal strain heterogeneity, strain
      patterning, and strain localization phenomena.

PMID- 16899373
TI  - Characterization and sequence verification of thiolated deoxyoligonucleotides
      used for microarray construction.
AB  - During synthesis of thiolated deoxyoligonucleotides, side products can be formed.
      When used in the fabrication of microchips, the oligonucleotides have to be of
      high purity. We demonstrated the presence of impurities, which were not failure
      sequences from the synthesis. These products were identified and characterized
      using high-performance liquid chromatography (HPLC) and electrospray MS(/MS). The
      presence of the free thiol group was assessed by acrylamide derivatization. After
      reaction with acrylamide the correct compounds showed a 71 u mass shift and the
      major fragment ions could be assigned as 5' a-base and 3' w ions, similar as for
      unmodified DNA. The side products were unaffected by acrylamide, suggesting that
      the thiol group was modified. The oligonucleotide containing a species with a
      mass of 32 u higher was identified as 5' sulfinic acid containing molecule and
      was found as 45% of the total amount of a DNA 25 mer. Other components appeared
      to be dithio-linked oxidation products, present about 1 to 5% in a 10 mer and 15
      mer deoxyoligonucleotide. The analyses were useful for optimizing the synthesis
      protocols.

PMID- 16899375
TI  - Examination of EMG normalisation methods for the study of the posterior and
      posterolateral neck muscles in healthy controls.
AB  - The purpose of this study was to examine the reliability of normalisation methods
      used in the study of the posterior and posterolateral neck muscles in a group of
      healthy controls. Six asymptomatic male subjects performed a total of 12 maximum
      voluntary isometric contractions (MVIC) and 60%-submaximal isometric contractions
      (60%-MVIC) against the torque arm of an isokinetic dynamometer whilst surface and
      intramuscular electromyography (EMG) was recorded unilaterally from
      representative posterior and posterolateral locations. Reliability was calculated
      using intra-class correlation coefficient (ICC), relative standard error of
      measurement (%SEM) and relative coefficient of variation (%CV). Maximal torque
      output was found to be highly reliable in the directions of extension and right
      lateral bending when the first of three MVIC contractions was excluded. When
      averaged across contraction direction, high reliability was found for both
      surface (MVIC: ICC=0.986, %SEM=7.5, %CV=9.2; 60%-MVIC: ICC=0.975, %SEM=10,
      %CV=13.7) and intramuscular (MVIC: ICC=0.910, %SEM=20, %CV=19.1; 60%-MVIC:
      ICC=0.952, %SEM=16.5, %CV=13.5) electrodes. Intramuscular electrodes displayed
      the least reliability in right lateral bending. The use of visual feedback
      markedly increased the reliability of 60%-MVIC contractions.

PMID- 16899376
TI  - How an abrupt onset cue can release motion-induced blindness.
AB  - In motion-induced blindness (MIB), a target within rotating random dots is
      occasionally hidden from observers' consciousness during observation. In the
      present study, a red ring-like cue was centered on a target and presented
      immediately after observers reported subjective disappearance of the target in
      MIB (Experiment 1). The radius of the cue was systematically modulated. Observers
      quickly regained awareness of the disappeared object only after they were
      provided with a pinpoint cue of its location. We also found that a flickering cue
      at 1Hz hindered MIB when the radius of the cue was critically small (Experiment
      2). Furthermore, abrupt onset of a small square was enough to regain awareness of
      the target (Experiment 3). Successful revival of the target with a small cue
      indicates that critical spatial distribution of visual attention determines what
      in the visual scene is included in visual awareness.

PMID- 16899377
TI  - Contingency learning without awareness: evidence for implicit control.
AB  - The results of four experiments provide evidence for controlled processing in the
      absence of awareness. Participants identified the colour of a neutral distracter
      word. Each of four words (e.g., MOVE) was presented in one of the four colours
      75% of the time (Experiments 1 and 4) or 50% of the time (Experiments 2 and 3).
      Colour identification was faster when the words appeared in the colour they were
      most often presented in relative to when they appeared in another colour, even
      for participants who were subjectively unaware of any contingencies between the
      words and the colours. An analysis of sequence effects showed that participants
      who were unaware of the relation between distracter words and colours nonetheless
      controlled the impact of the word on performance depending on the nature of the
      previous trial. A block analysis of contingency-unaware participants revealed
      that contingencies were learned rapidly in the first block of trials. Experiment
      3 showed that the contingency effect does not depend on the level of awareness,
      thus ruling out explicit strategy accounts. Finally, Experiment 4 showed that the
      contingency effect results from behavioural control and not from semantic
      association or stimulus familiarity. These results thus provide evidence for
      implicit control.

PMID- 16899378
TI  - Vagus nerve stimulation: clinical experience in drug-resistant pediatric
      epileptic patients.
AB  - INTRODUCTION: Vagus nerve stimulation (VNS) is an effective alternative treatment
      for patients with partial refractory epilepsy. Nevertheless, information
      regarding VNS in children is still limited. MATERIALS AND METHODS: The clinical
      efficacy, safety and neuropsychological effects of VNS in 34 children (mean age
      11.5 years) with drug-resistant epilepsy were studied. Mean follow-up was 30.8
      months. Nine patients have been diagnosed with Lennox-Gastaut Syndrome, nine
      patients were affected by severe partial epilepsy with bisynchronous EEG and drop
      attacks, and 16 patients suffered from partial epilepsy without bisynchronous EEG
      and fall seizures. Forms were designed for prospective data collection on each
      patient's history, seizures, implants, device settings, quality of life (QOL),
      neuropsychological assessment and adverse events. Surgical technique was
      performed both by standard two incisions and single neck incision. RESULTS: Mean
      reduction in total seizures was 39% at 3 months, 38% at 6 months, 49% at 12
      months, 61% at 24 months and 71% at 36 months. Significant better results were
      obtained in partial epilepsy, with and without drop attacks, than in Lennox
      Gastaut syndrome--three patients being seizure-free. No operative morbidity was
      reported. Side-effects were minor and transient--the most common were voice
      alteration and coughing during stimulation. In two patients, electrode breakage
      occurred 3 years after surgical procedure; in both cases, a new device was
      implanted after removing the vagal electrode coils and generator. CONCLUSION: VNS
      can be considered an appropriate strategy as an add-on treatment in children
      affected by drug-resistant partial epilepsy and ineligible for resective epilepsy
      surgery.

PMID- 16899380
TI  - Epizootic lymphangitis: the impact on subsistence economies and animal welfare.

PMID- 16899379
TI  - Effect of endogenous and exogenous nitric oxide on calcium sparks as targets for
      vasodilation in rat cerebral artery.
AB  - The potent vasodilator nitric oxide (NO), produced mainly by the endothelium,
      acts through a BK(Ca)-dependent mechanism to increase the frequency of calcium
      sparks (Ca(2+) sparks) in myocyte isolated from rat cerebral arteries. Our
      present aim has been to assess the role of endogenous and exogenous NO on the
      Ca(2+) sparks through ryanodine-sensitive channels in the sarcoplasmic reticulum
      of an intact artery. Calcium sparks, detected with fluo-4 and laser scanning
      confocal microscopy, were examined in isolated pressurized rat posterior cerebral
      arteries with (intact) and without endothelium (denuded). Addition of the NO
      donor, DEA-NONOate (N-(2-aminoethyl)-N-(2-hydroxy-2-nitrosohydrazino)-1,2
      ethylenediamine), did not change the amplitude and frequency of Ca(2+) sparks in
      the intact artery. However, inhibition of nitric oxide synthase with N-omega
      nitro-L-arginine or removal of endothelium reduced Ca(2+) sparks frequency by
      about 50%. Under these conditions (i.e., absence of endogenous NO production),
      DEA-NONOate, increased Ca(2+) spark frequency 3- to 4-fold. These results suggest
      that endothelial NO modulates local Ca(2+) release events in the arterial smooth
      muscle and that this mechanism may contribute to the actions of
      nitrovasodilators.

PMID- 16899381
TI  - Selective fatty acid mobilization in the American mink (Mustela vison) during
      food deprivation.
AB  - The mobilization of fatty acids (FAs) during food deprivation is a selective
      process in laboratory rodents and humans. The site-specific differences in
      adipose tissue functions - e.g. energy storage versus insulation - should also
      affect the use of different FAs. To study this, 16 female minks were randomly
      assigned into the control group or fasted for 5 days. Preferential mobilization
      of n-3 polyunsaturated FAs (PUFAs) during fasting caused a decrease in the n-3/n
      6 PUFA ratio in fat and liver. In addition, the minks utilized short-chain FAs
      efficiently in all fat depots, but long-chain FAs - 20:0, 20:1n-11, 20:1n-9,
      22:1n-11 and 24:1n-9 - were preserved. The number of double bonds in the FA chain
      correlated positively with mobilization rate in the retroperitoneal fat. The
      observed negative correlation between mobilization rate and the location of the
      first double bond from the methyl end may be due to peroxisomal chain-shortening
      of long-chain FAs and not the double bond position per se. As a result, minks are
      able to preserve a low melting point and fluidity of the subcutaneous fat depots,
      which would be essential to a Northern semi-aquatic mammal.

PMID- 16899382
TI  - Overexpression of GAMT restores GAMT activity in primary GAMT-deficient
      fibroblasts.
AB  - Guanidinoacetate methyltransferase deficiency (MIM 601240) is an autosomal
      recessive disorder of creatine biosynthesis. Patients present with mental
      retardation, extrapyramidal symptoms, autistic-like behavior, epilepsy, cerebral
      creatine deficiency and increased levels of guanidinoacetate. So far 15 mutations
      have been reported, including six missense variants that are highly likely to be
      pathogenic mutations. To prove that mutations in the GAMT gene are responsible
      for GAMT deficiency we overexpressed the GAMT open reading frame in GAMT
      deficient fibroblasts by stable transfection. In addition, HeLa cells were
      transiently transfected with the same expression vector. In contrast to mock
      transfectants transfection of primary GAMT-deficient fibroblasts with wild-type
      GAMT results in the restoration of GAMT activity as measured by GC-MS using
      stable isotope labeled substrates. Moreover, the expression of the GAMT-EGFP
      fusion protein was analyzed by Western blot, confirming the presence of GAMT
      fusion protein, both in the stable as well as in the transient transfectants.
      Here, we prove that mutations in the GAMT gene are responsible for GAMT
      deficiency, since overexpression of the GAMT open reading frame restores GAMT
      activity in GAMT-deficient fibroblasts. Furthermore, the transient transfection
      of HeLa cells will be important for functional analysis of variants of unknown
      consequence (i.e., missense mutations).

PMID- 16899384
TI  - Fatal dengue hemorrhagic fever in adults during a dengue epidemic in Singapore.
AB  - BACKGROUND: Dengue fever has seen a significant re-emergence in Southeast Asia.
      Associated with the rise of dengue has been the increase in dengue-associated
      mortality. To better understand the predictors of mortality, we conducted a
      review of hospitalized adult dengue infections within our institution. METHODS:
      This was a retrospective case-control study of dengue-associated deaths at a
      large tertiary care hospital. RESULTS: In 2004, of 3186 cases of dengue fever
      (DF)/hemorrhagic dengue fever (DHF) admitted to our institution, there were 130
      cases of DHF and seven dengue-associated deaths (case-fatality rate 5.4%). At
      least three of the seven fatal cases had serological evidence of primary dengue
      infection. All dengue-mortality cases had rapidly progressive clinical
      deterioration at an average of day 4 of fever with intensive care admission
      occurring on a mean of 5.6 days of fever. Adult respiratory distress syndrome,
      disseminated intravascular coagulopathy, and multi-organ failure were the most
      common causes of death despite early hospitalization, intravenous fluid, and
      blood-product support. CONCLUSION: Dengue is associated with severe disease, and
      deaths do occur despite current supportive management. Fatal DHF/dengue shock
      syndrome (DSS) does occur in adults and in primary dengue infection. Better early
      predictors of disease severity and clinical interventions are needed.

PMID- 16899383
TI  - Gene expression profiles of homogentisate-treated Fah-/- Hpd-/-mice using DNA
      microarrays.
AB  - Hereditary tyrosinemia I (HT I) is a genetic disorder of tyrosine metabolism
      caused by abnormalities of fumarylacetoacetate hydrolase. Disturbances in
      tyrosine metabolism lead to increased levels of succinylacetone and
      succinylacetoacetate. However, the mechanisms causing liver failure, cirrhosis,
      renal tubular dysfunction, and hepatocarcinoma are still unknown. Alterations in
      gene expression found in the livers of patients with HT I are responsible for the
      pathogenesis of this disease, for example acute liver failure. Therefore, gene
      expression analysis allows us to better understand its pathogenesis. We analyzed
      gene expressions in tyrosinemia type I model mice with liver failure using
      microarrays. The results were confirmed by quantitative PCR to evaluate the
      pathogenesis of tyrosinemia type I. We found that numerous genes, including amino
      acid metabolism and apoptosis related genes, were up- or down-regulated at the
      onset of liver failure. These findings are useful in understanding the
      pathogenesis of hereditary tyrosinemia.

PMID- 16899385
TI  - Containing a large bioterrorist smallpox attack: a computer simulation approach.
AB  - BACKGROUND: A bioterrorist release of smallpox is a constant threat to the
      population of the USA and other countries. DESIGN: A stochastic simulation model
      of the spread of smallpox due to a large bioterrorist attack in a structured
      population was constructed. Disease natural history parameter estimates, time
      lines of behavioral activities, and control scenarios were based on the
      literature and on the consensus opinion of a panel of smallpox experts. RESULTS:
      The authors found that surveillance and containment, i.e., isolation of known
      cases and vaccination of their close contacts, would be sufficient to effectively
      contain a large intentional smallpox release. Given that surveillance and
      containment measures are in place, preemptive vaccination of hospital workers
      would further reduce the number of smallpox cases and deaths but would require
      large numbers of prevaccinations. High levels of reactive mass vaccination after
      the outbreak begins would further reduce smallpox cases and deaths to a minimum,
      but would require even larger numbers of vaccinations. Reactive closure of
      schools would have a minimal effect. CONCLUSION: A rapid and well-organized
      response to a bioterrorist attack would be necessary for effective surveillance
      and containment to control spread. Preemptive vaccination of hospital workers and
      reactive vaccination of the target population would further limit spread, but at
      a cost of many more vaccinated. This cost in resources and potential harm due to
      vaccination will have to be weighed against the potential benefits should an
      attack occur. Prevaccination of the general population is not necessary.

PMID- 16899386
TI  - Direct, quantitative clinical assessment of hand function: usefulness and
      reproducibility.
AB  - Methods of assessing functional impairment in arthritic hands include pain
      assessments and disability scoring scales which are subjective, variable over
      time and fail to take account of the patients' need to adapt to deformities. The
      aim of this study was to evaluate measures of functional strength and joint
      motion in the assessment of the rheumatoid (RA) and osteoarthritic (OA) hand. Ten
      control subjects, ten RA and ten OA patients were recruited for the study. All
      underwent pain and disability scoring and functional assessment of the hand using
      measures of pinch/grip strength and range of joint motion (ROM). Functional
      assessments including ROM analyses at interphalangeal (IP), metacarpophalangeal
      (MCP) and wrist joints along with pinch/grip strength clearly discriminated
      between patient groups (RA vs. OA MCP ROM P<0.0001), pain and disability scales
      were unable to. In the RA there were demonstrable relationships between ROM
      measurements and disability (R2=0.31) as well as disease duration (R2=0.37).
      Intra-patient measures of strength were robust whereas inter-patient comparisons
      showed variability. In conclusion, pinch/grip strength and ROM are clinically
      reproducible assessments that may more accurately reflect functional impairment
      associated with arthritis.

PMID- 16899387
TI  - Neurodynamic responses in children with migraine or cervicogenic headache versus
      a control group. A comparative study.
AB  - Headache in children with unknown aetiology is an increasing phenomenon in
      industrial countries, especially during growth spurts. During this growth phase,
      the Long Sitting Slump (LSS) can be a useful tool for measurement of
      neurodynamics and management. This study investigated the difference in cervical
      flexion and sensory responses (intensity and location) during the LSS tests in
      children (n=123) aged 6-12 years, between a migraine (primary headache group=PG),
      cervicogenic headache (secondary headache group=SG) and control group (CG). The
      results indicated that the intensities of the sensory response rate were highest
      in the PG and SG when compared to CG. The responses in the legs were
      predominantly found in the PG (81.9%) and responses in the spine in the SG (80%).
      The sacrum position varied significantly between both headache groups (PG and SG)
      and the CG (p<0.0001), but there was no significant difference between the CG and
      the PG (p>0.05). No significant difference in the neck flexion range was measured
      in LSS, nor in standardized knee flexion between the PG and CG (p>0.05). The
      cervical flexion ranges differed significantly (p<0.0001) between the SG on the
      one hand and the PG and CG on the other. The biggest difference in neck flexion
      during knee extension was between the SG and CG.

PMID- 16899388
TI  - Recruitment of the deep cervical flexor muscles during a postural-correction
      exercise performed in sitting.
AB  - Specific strategies to optimally facilitate postural muscles to retrain postural
      form are advocated in the clinical management of neck pain. The purpose of this
      study was to compare the activation of selected cervical, thoracic and lumbar
      muscles during independent and facilitated postural correction in sitting in 10
      subjects with chronic neck pain. Deep cervical flexor (DCF) muscle activity was
      recorded with custom electrodes inserted via the nose and fixed by suction to the
      posterior mucosa of the oropharynx. Surface electrodes were placed over the
      thoracic erector spinae and lumbar multifidus muscles. Root-mean-square EMG
      amplitude was measured for each muscle across two conditions. In the first
      condition, subjects were instructed to spontaneously "sit up straight" from a
      slumped posture without any other guidance from the therapist. In the second
      condition the therapist provided specific manual and verbal facilitation to
      assist the patient to correct to an upright pelvic position with a neutral spinal
      lumbo-pelvic position. Activation of the DCF and lumbar multifidus muscles
      (P<0.05) were significantly greater when the therapist facilitated postural
      correction compared to independent sitting correction. Specific postural
      correction strategies result in better facilitation of key postural muscles
      compared to non-specific postural advice. The results of this study highlight the
      need for clinical skill and precision in postural training of patients with neck
      pain.

PMID- 16899389
TI  - Photodynamic activity of a new sensitizer derived from porphyrin-C60 dyad and its
      biological consequences in a human carcinoma cell line.
AB  - The photokilling activity of a porphyrin-C(60) (P-C(60)) dyad was evaluated on a
      Hep-2 human larynx-carcinoma cell line. This study represents the first
      evaluation of a dyad, with high capacity to form a photoinduced charge-separated
      state, to act as agent to inactivate cells by photodynamic therapy (PDT). Cell
      treatment was carried out with 1 microM P-C(60) incorporated into liposomal
      vesicles. No dark cytotoxicity was observed using 1 microM P-C(60) concentration
      and during long incubation time (24h). The uptake of sensitizer into Hep-2 was
      studied at different times of incubation. Under these conditions, a value of 1.5
      nmol/10(6)cells was found after 4h of incubation showing practically no change
      even after 24h. The cell survival after irradiation of the cells with visible
      light was dependent upon light exposure level. A high photocytotoxic effect was
      observed for P-C(60), which inactivated 80% of the cells after 54 J/cm(2) of
      irradiation. Moreover, the dyad kept a high photoactivity even under argon
      atmosphere. Thus, depending on the microenvironment where the sensitizer is
      localized, this compound could produce a biological photodamage through either a
      (1)O(2)-mediated photoreaction process or a free radical mechanism under low
      oxygen concentration. The mechanism of cell death was analyzed by Hoechst-33258,
      toluidine blue staining, TUNEL and DNA fragmentation. Cell cultures treated for
      24h with P-C(60) and irradiated with a dose of 54 J/cm(2) showed a great amount
      of apoptotic cells (58%). Moreover, changes in cell morphology were analyzed
      using fluorescence microscopy with Hoechst-33258 under low oxygen concentration.
      Under this anaerobic condition, necrotic cellular death predominated on apoptotic
      pathway. There were more apoptotic cells under air irradiation condition than
      under argon irradiation condition. To determine the apoptotic pathway, caspase-3
      activation was studied by caspase-3 activity detection kits. The last results
      showed that P-C(60) induced apoptosis by caspase-3-dependent pathway. These
      results indicated that molecular dyad, which can form a photoinduced charge
      separated state, is a promising model for phototherapeutic agents and they have
      potential application in cell inactivation by PDT.

PMID- 16899390
TI  - Nitric oxide-induced endoplasmic reticulum stress activates the expression of
      cargo receptor proteins and alters the glycoprotein transport to the Golgi
      complex.
AB  - The endoplasmic reticulum Golgi intermediate compartment 53 protein recycles
      continuously between the endoplasmic reticulum and the Golgi complex and ensures
      the anterograde transport of specific glycoproteins with the assistance of the
      Multiple Clotting Factor Deficiency adaptor protein. Therefore, to analyze the
      effect of the endoplasmic reticulum stress on the secretory pathway beyond the
      endoplasmic reticulum, we analyzed the expression of both proteins in J774
      macrophages incubated with the nitric oxide donor DETA NONOate or with
      thapsigargin. Both proteins accumulated progressively, by a transcriptional
      mechanism, in response to these inducers. Nitric oxide also induced a higher
      level of calreticulin and glucose regulated 78 protein, two endoplasmic reticulum
      proteins controlled by the unfolded protein response. Interestingly, nitric oxide
      induced the processing of the activating transcription factor 6alpha of the
      unfolded protein response, while thapsigargin also induced the activation of the
      transcription factor X-box Binding Protein 1. In addition, we showed that the
      accumulation of both transporters occurred simultaneously with the activation of
      endoplasmic reticulum-stress-dependent apoptosis, suggesting that these proteins
      may participate in the events that will eventually decide the fate of the cell.
      Induction of endoplasmic reticulum stress affected the rate of anterograde
      transport of a reporter glycoprotein, indicating that the endoplasmic reticulum
      to Golgi transport is remarkably impaired. Our results indicate that increased
      levels of cargo receptor proteins might have a function either in the quality
      control of protein folding in the endoplasmic reticulum or in the homeostasis of
      the intermediate compartment and Golgi complex during cell stress.

PMID- 16899391
TI  - Interactions between nitrogen and cytokinin in the regulation of metabolism and
      development.
AB  - Inorganic nitrogen is a substrate for nitrogen assimilation and also functions as
      a signal triggering widespread changes in gene expression that modulate
      metabolism and development. To integrate the actions of the nitrogen signal at
      the whole plant level, plants use multiple signaling routes that communicate
      internal and external nitrogen status. One route depends on nitrate itself and
      one uses cytokinin as a messenger. Recent genome-wide research has shown that the
      nitrate-specific signal regulates a wide variety of metabolic processes including
      nitrogen and carbon metabolism, and cytokinin biosynthesis. Cytokinin-mediated
      signaling is related to the control of development, protein synthesis and
      acquisition of macronutrients. The coordination and interaction of both
      regulatory pathways is important for normal plant growth under variable nitrogen
      supply conditions.

PMID- 16899392
TI  - Deformable registration of diffusion tensor MR images with explicit orientation
      optimization.
AB  - In this paper, we present a novel deformable registration algorithm for diffusion
      tensor MR images that enables explicit optimization of tensor reorientation. The
      optimization seeks a piecewise affine transformation that divides the image
      domain into uniform regions and transform each region affinely. The objective
      function captures both the image similarity and the smoothness of the
      transformation across region boundaries. The image similarity enables explicit
      orientation optimization by incorporating tensor reorientation, which is
      necessary for warping diffusion tensor images. The objective function is
      formulated in a way that allows explicit implementation of analytic derivatives
      to drive fast and accurate optimization using the conjugate gradient method. By
      explicitly optimizing tensor reorientation, the algorithm is designed to take
      advantage of similarity measures comparing tensors as a whole. The optimal
      transformation is hierarchically refined in a subdivision framework. A comparison
      with affine registration for inter-subject normalization of 8 subjects shows that
      the proposed algorithm improves the alignment of several major white matter
      structures examined: the anterior thalamic radiations, the inferior fronto
      occipital fasciculi, the corticospinal/corticobulbar tracts and the genu and the
      splenium of the corpus callosum. The alignment of white matter structures is
      assessed using a novel scheme of computing distances between the corresponding
      fiber bundles derived from tractography.

PMID- 16899393
TI  - Genes and domain specificity.

PMID- 16899395
TI  - Remembering the time: a continuous clock.
AB  - The neural mechanisms for time measurement are currently a subject of much
      debate. This article argues that our brains can measure time using the same
      dorsolateral prefrontal cells that are known to be involved in working memory.
      Evidence for this is: (1) the dorsolateral prefrontal cortex is integral to both
      cognitive timing and working memory; (2) both behavioural processes are modulated
      by dopamine and disrupted by manipulation of dopaminergic projections to the
      dorsolateral prefrontal cortex; (3) the neurons in question ramp their activity
      in a temporally predictable way during both types of processing; and (4) this
      ramping activity is modulated by dopamine. The dual involvement of these
      prefrontal neurons in working memory and cognitive timing supports a view of the
      prefrontal cortex as a multipurpose processor recruited by a wide variety of
      tasks.

PMID- 16899396
TI  - What's so special about the average face?
AB  - The past few years have seen a marked increase in our understanding of how faces
      are represented in the brain, with the discovery of new anatomical structures and
      new algorithms for representing faces. Still, the basic computational mechanism
      used by the primate visual system to identify faces remains a topic of intense
      debate. Are faces represented by matching to a set of stored exemplars, or by
      measuring the distance from a standard prototype along a set of different axes? A
      recent article by Rhodes and Jeffery provides compelling psychophysical evidence
      in favor of the latter 'axis' model.

PMID- 16899397
TI  - Beyond mind-reading: multi-voxel pattern analysis of fMRI data.
AB  - A key challenge for cognitive neuroscience is determining how mental
      representations map onto patterns of neural activity. Recently, researchers have
      started to address this question by applying sophisticated pattern-classification
      algorithms to distributed (multi-voxel) patterns of functional MRI data, with the
      goal of decoding the information that is represented in the subject's brain at a
      particular point in time. This multi-voxel pattern analysis (MVPA) approach has
      led to several impressive feats of mind reading. More importantly, MVPA methods
      constitute a useful new tool for advancing our understanding of neural
      information processing. We review how researchers are using MVPA methods to
      characterize neural coding and information processing in domains ranging from
      visual perception to memory search.

PMID- 16899398
TI  - The causal psycho-logic of choice.
AB  - Choices do not merely identify one option among a set of possibilities; choosing
      is an intervention, an action that changes the world. As a result, good decision
      making generally requires a model specifying how actions are causally related to
      outcomes. Interventions license different inferences than observations because an
      event whose state has been determined by intervention is not diagnostic of the
      normal causes of that event. We integrate these ideas into a causal framework for
      decision making based on causal Bayes nets theory, and suggest that deliberate
      decision making is based on simplified causal models and imaginary interventions.
      The framework is consistent with what we know so far about how people make
      decisions.

PMID- 16899399
TI  - The missing whole in perceptual models of perirhinal cortex.

PMID- 16899400
TI  - The simpler syntax hypothesis.
AB  - What roles do syntax and semantics have in the grammar of a language? What are
      the consequences of these roles for syntactic structure, and why does it matter?
      We sketch the Simpler Syntax Hypothesis, which holds that much of the explanatory
      role attributed to syntax in contemporary linguistics is properly the
      responsibility of semantics. This rebalancing permits broader coverage of
      empirical linguistic phenomena and promises a tighter integration of linguistic
      theory into the cognitive scientific enterprise. We suggest that the general
      perspective of the Simpler Syntax Hypothesis is well suited to approaching
      language processing and language evolution, and to computational applications
      that draw upon linguistic insights.

PMID- 16899401
TI  - Whorf versus Socrates, round 10.
AB  - A recent paper by Dehaene, Izard, Pica and Spelke examined geometric concepts
      among the Munduruku, an Amazonian group without many linguistic terms for spatial
      relations, and without maps or formal schooling. Their profile of strengths and
      weaknesses provides new insights into the nature of the human mind and the
      importance of culture and language to the development of thought.

PMID- 16899402
TI  - What's new in antibiotic resistance? Focus on beta-lactamases.
AB  - In gram-negative bacteria, beta-lactamases are the most important mechanism of
      resistance to beta-lactam antibiotics. Currently, the beta-lactamases receiving
      the most attention are the extended-spectrum beta-lactamases (ESBLs), inhibitor
      resistant beta-lactamases and carbapenemases. When found in Escherichia coli and
      Klebsiella spp., ESBLs confer resistance to extended-spectrum cephalosporins,
      such as ceftazidime, cefotaxime and cefepime. Hence, ESBLs limit the choice of
      beta-lactam therapy to carbapenems. A worrisome trend is the increasing number of
      pathogens found in isolates from patients in the community that possess ESBLs. It
      is equally distressing that carbapenemases (serine and metallo-beta-lactamases)
      are being found in many of the same bacteria that harbor ESBLs, for example
      Klebsiella pneumoniae. Despite many years studying beta-lactamases, important
      clinical and scientific questions still remain.

PMID- 16899403
TI  - Copying and pasting of examinations within the electronic medical record.
AB  - Electronic patient records often include text that has been copied and pasted
      from other records. A type of copying that involves the highest risk for
      confusion, medical error, and medico-legal harm is the copying of the clinical
      examination. We studied this phenomenon using an automated text categorization
      algorithm to detect copied exams in a set of 167,076 VA records. Exam copying
      occurred frequently, in about 3% of all exams, or in 25% of patient charts.
      Thirteen percent of all authors had copied at least one exam, and 3% of authors
      had copied an exam from another author. There were significant differences
      between service types and levels of training of the authors. We speculate that
      copying and pasting of exams degrades the quality of the medical record, and that
      studying this behavior is integral to our understanding of phenomenology of the
      electronic medical record.

PMID- 16899404
TI  - Molecular evidence of fungal signatures in the marine protist Corallochytrium
      limacisporum and its implications in the evolution of animals and fungi.
AB  - Fungi, animals, and single-celled organisms belonging to the choanozoans together
      constitute the supergroup Opisthokonta. The latter are considered crucial in
      understanding the evolutionary origin of animals and fungi. The choanozoan
      Corallochytrium limacisporum is an enigmatic marine protist of considerable
      interest in opisthokontan evolution. Several isolates of the organism were
      obtained from a coral reef lagoon in the Lakshadweep group of islands of the
      Arabian Sea. The capability of these cultures to grow on media containing
      inorganic nitrogen sources prompted us to examine the possible presence of fungal
      signatures, namely the enzyme alpha-aminoadipate reductase (alpha-AAR) involved
      in the alpha-aminoadipate (AAA) pathway for synthesizing lysine and ergosterol,
      in one of the isolates. These features, as well as the sterol C-14 reductase gene
      involved in the sterol pathway of animals and fungi, were detected in the
      organism. Phylogenetic trees based on the alpha-AAR gene suggested that
      Corallochytrium limacisporum is a sister clade to fungi, while those based on the
      C-14 reductase gene did not adequately resolve whether the organism was more
      closely related to fungi or animals. While many studies indicate that
      Corallochytrium is a sister clade to animals, we suggest that further studies are
      required to examine whether this protist is in fact more closely related to fungi
      rather than to animals.

PMID- 16899405
TI  - Anti-MRSA beta-lactams in development.
AB  - Ceftobiprole medocaril, the most advanced of the anti-MRSA (methicillin-resistant
      Staphylococcus aureus) beta-lactams in clinical development, has recently
      completed its first Phase III clinical trial, and has demonstrated non
      inferiority to vancomycin. Phase II clinical trials have been initiated with
      PPI0903, which is, like ceftobiprole medocaril, an injectable pro-drug of a broad
      spectrum cephalosporin with anti-MRSA activity, and with RO4908643, a carbapenem
      with more modest activity against MRSA.

PMID- 16899406
TI  - Deconvoluting the effects of P-glycoprotein on intestinal CYP3A: a major
      challenge.
AB  - Metabolism by cytochrome P4503A (CYP3A) and P-glycoprotein (P-gp)-mediated efflux
      are two important biochemical barriers to drug absorption from the intestine.
      CYP3A, the most important family of drug-metabolizing enzymes, shares many
      substrates with the efflux transporter P-gp. Although the individual impact of
      these two systems on drug disposition is routinely assessed, the effect of both
      systems acting together during intestinal absorption is difficult to ascertain.
      Pharmacokinetic theory predicts that the effect of efflux on overall metabolism
      depends on substrate concentrations relative to the respective kinetic parameters
      of these processes (i.e. affinities for transport and metabolism, as well as the
      capacities of these processes). Researchers have published conflicting findings
      on how efflux affects metabolism. Furthermore, the in vitro parameters that have
      been used to explain or predict this interation are more relevant for describing
      overall changes in extraction efficiency of the system (intestinal epithelium),
      rather than deconvoluting the effect of P-gp on CYP3A-mediated metabolism.
      Developing a more refined way to understand this interplay and its potential
      relevance to drug absorption is an important goal, as a large proportion of
      marketed drugs and many modern drug discovery candidates are known to be affected
      by one or both of these proteins.

PMID- 16899407
TI  - MITF: master regulator of melanocyte development and melanoma oncogene.
AB  - Microphthalmia-associated transcription factor (MITF) acts as a master regulator
      of melanocyte development, function and survival by modulating various
      differentiation and cell-cycle progression genes. It has been demonstrated that
      MITF is an amplified oncogene in a fraction of human melanomas and that it also
      has an oncogenic role in human clear cell sarcoma. However, MITF also modulates
      the state of melanocyte differentiation. Several closely related transcription
      factors also function as translocated oncogenes in various human malignancies.
      These data place MITF between instructing melanocytes towards terminal
      differentiation and/or pigmentation and, alternatively, promoting malignant
      behavior. In this review, we survey the roles of MITF as a master lineage
      regulator in melanocyte development and its emerging activities in malignancy.
      Understanding the molecular function of MITF and its associated pathways will
      hopefully shed light on strategies for improving therapeutic approaches for these
      diseases.

PMID- 16899408
TI  - DNA damage-induced cell death by apoptosis.
AB  - Following the induction of DNA damage, a prominent route of cell inactivation is
      apoptosis. During the last ten years, specific DNA lesions that trigger apoptosis
      have been identified. These include O6-methylguanine, base N-alkylations, bulky
      DNA adducts, DNA cross-links and DNA double-strand breaks (DSBs). Repair of these
      lesions are important in preventing apoptosis. An exception is O6-methylguanine
      thymine lesions, which require mismatch repair for triggering apoptosis.
      Apoptosis induced by many chemical genotoxins is the consequence of blockage of
      DNA replication, which leads to collapse of replication forks and DSB formation.
      These DSBs are thought to be crucial downstream apoptosis-triggering lesions.
      DSBs are detected by ATM (ataxia telangiectasia mutated) and ATR (ataxia
      telangiectasia and Rad3 related) proteins, which signal downstream to CHK1, CHK2
      (checkpoint kinases) and p53. p53 induces transcriptional activation of pro
      apoptotic factors such as FAS, PUMA and BAX. Many tumors harbor mutations in p53.
      There are p53 backup systems that involve CHK1 and/or CHK2-driven E2F1 activation
      and p73 upregulation, which in turn transcribes BAX, PUMA and NOXA. Another
      trigger of apoptosis upon DNA damage is the inhibition of RNA synthesis, which
      leads to a decline in the level of critical gene products such as MKP1 (mitogen
      activated protein kinase phosphatase). This causes sustained activation of JNK
      (Jun kinase) and, finally, AP-1, which stimulates death-receptor activation. DNA
      damage-triggered signaling and execution of apoptosis is cell-type- and genotoxin
      specific depending on the p53 (p63 and p73) status, death-receptor
      responsiveness, MAP-kinase activation and, most importantly, DNA repair capacity.
      Because most clinical anti-cancer drugs target DNA, increasing knowledge on DNA
      damage-triggered signaling leading to cell death is expected to provide new
      strategies for therapeutic interventions.

PMID- 16899410
TI  - Cardiac rehabilitation, secondary prevention or chronic disease management? Do we
      need a name change?

PMID- 16899409
TI  - Recombinant guinea pig TNF-alpha enhances antigen-specific type 1 T lymphocyte
      activation in guinea pig splenocytes.
AB  - TNF-alpha is a principal pro-inflammatory cytokine which contributes to the
      activation of innate immunity and the transition to antigen-specific adaptive
      immunity in tuberculosis. Using recombinant guinea pig (rgp) TNF-alpha, the
      effect of TNF-alpha on lymphocyte activation was examined in unvaccinated and BCG
      vaccinated guinea pigs. Splenocytes were stimulated with PPD or ConA, in the
      presence or absence of rgp TNF-alpha for 96 h. Lymphocyte proliferation was
      measured using [(3)H]thymidine uptake, and IL-12 p40 and IFN-gamma mRNA were
      analyzed using real-time PCR. rgpTNF-alpha alone was able to stimulate a
      significant degree of proliferation in splenocytes. The addition of rgpTNF-alpha
      to PPD-stimulated cells enhanced the proliferation of splenocytes from BCG
      vaccinated guinea pigs. Furthermore, enhancement of proliferation by rgpTNF-alpha
      was found to be correlated with upregulation of the levels of Type 1 cytokine
      mRNA (IL-12p40 and IFN-gamma) in splenocyte cultures. This suggests that TNF
      alpha plays an important role in the regulation of Type 1 T cell-mediated immune
      responses in the guinea pig.

PMID- 16899411
TI  - Hemimegalencephalic appearance of normal hemisphere in unilateral heterotopia and
      absent corpus callosum.
AB  - We report two patients with medically refractory epilepsy who had MRI evidence of
      unilateral subcortical nodular heterotopia and agenesis of corpus callosum. The
      abnormal hemisphere was small, whereas the contralateral normal hemisphere
      appeared large and crossed the midline. Although the normal hemisphere was
      initially mistaken for hemimegalencephaly, there were no typical radiological
      features. Moreover, the electroencephalographic abnormalities lateralized to the
      hemisphere showing heterotopia. Because contralateral hemispheric abnormalities
      like heterotopia, hemimicrencephaly, and hemimegalencephaly can occur in patients
      with hemispheric heterotopias, we emphasize the importance of careful scrutiny of
      the contralateral hemisphere in patients with unilateral heterotopia. Absence of
      typical radiological features and appropriately lateralized
      electroencephalographic abnormalities will help differentiate the two. This is
      crucial when planning epilepsy surgery.

PMID- 16899412
TI  - Workflow modeling in critical care: piecing together your own puzzle.
AB  - The intensive care unit (ICU) is an instance of a very dynamic health care
      setting where critically ill patients are being managed. To provide good care, an
      extensive and coordinated communication amongst the role players, use of numerous
      information systems and operation of devices for monitoring and treatment
      purposes are required. The purpose of this research is to study error evolution
      and management within this environment. The focus is on representing the workflow
      of critical care environment, which emphasizes the importance such a
      representation may play in strategizing the management of medical errors. We used
      ethnographic observation and interview data to build individual pieces of the
      workflow, dependent on the individual and the activity concerned. Key personnel
      were intensively followed during their respective patient care activities and the
      related actions. All interactions were recorded for analysis. These clinicians
      and nurses were interviewed to complement the observation data and to delineate
      their individual workflows. These pieces of the ICU workflow were used to develop
      a generalize-able cognitive model to represent the intricate workflow applicable
      to other health care settings. The proposed model can be used to identify and
      characterize medical errors and for error prediction in practice.

PMID- 16899413
TI  - Noradrenaline is necessary for the hedonic properties of addictive drugs.
AB  - To determine whether noradrenaline (NA) is an essential neurotransmitter for
      addictive and appetitive behaviors, we measured drug and food seeking in
      transgenic mice lacking dopamine beta-hydroxylase (Dbh), the enzyme responsible
      for synthesizing NA. Using the conditioned place preference test (CPP), we show
      that Dbh -/- mice do not exhibit rewarding behavior to morphine, cocaine, or the
      mixed reuptake inhibitor bupropion. In spite of their lack of preference for
      drugs, Dbh -/- mice had an unaltered preference for food. Drug seeking was
      induced when NA was restored to the central nervous system of Dbh -/- mice by
      administration of l-threo-3,4-dihydroxyphenylserine (DOPS) and carbidopa. When a
      NK1 receptor antagonist was co-administered with morphine or cocaine, it produced
      aversive behavior in Dbh -/- mice while it abolished place preference in the
      controls. NK1 antagonists alone did not have any rewarding or aversive effect in
      the CPP suggesting that substance P opposes some of the unpleasant effects of
      morphine and cocaine. Our results show that NAergic transmission is necessary for
      motivated behaviors, the dysregulation of which is a co-morbid factor of many
      depressive states. The reversibility of this phenomenon, by restoring NA,
      indicates that even when this behavioral deficit is genetically determined it can
      be reversed.

PMID- 16899415
TI  - Process economics of industrial monoclonal antibody manufacture.
AB  - Pressures for cost-effective manufacture of antibodies are growing given their
      high doses and increasing market potential that have resulted in significant
      increases in total site capacities of up to 200,000 L. This paper focuses on the
      process economic issues associated with manufacturing antibodies and reviews the
      cost studies published in the literature; many of the issues highlighted are not
      only specific to antibodies but also apply to recombinant proteins. Data collated
      at UCL suggest current benchmark investment costs of $660-$1580/ft2 ($7130
      $17,000/m2) and $1765-$4220/L for antibody manufacturing facilities with total
      site capacities in the range of 20,000-200,000 L; the limitations of the data are
      highlighted. The complications with deriving benchmark cost of goods per gram
      (COG/g) values are discussed, stressing the importance of stating the annual
      production rate and either titre or fermentation capacity with the cost so as to
      allow comparisons. The uses and limitations of the methods for cost analysis and
      the available software tools for process economics are presented. Specific
      examples found in the literature of process economic studies related to antibody
      manufacture for different expression systems are reviewed. The key economic
      drivers are identified; factors such as fermentation titre and overall yield are
      critical determinants of economic success. Future trends in antibody manufacture
      that are driven by economic pressures are discussed, such as the use of
      alternative expression systems (e.g. transgenics, E. coli and yeast),
      disposables, and improvements to downstream technology. The hidden costs and the
      challenges in each case are highlighted.

PMID- 16899416
TI  - Isotachophoresis preconcentration integrated microfluidic chip for highly
      sensitive genotyping of the hepatitis B virus.
AB  - The genotyping of hepatitis B virus (HBV) has become recently a valuable tool not
      only for epidemiological reasons but also for the clinical practice. Conventional
      methods for HBV genotyping typically include amplification of the target DNA
      sequences with a two-round nested PCR followed by separation of the amplified
      fragments by gel electrophoresis. A microfluidic chip that couples
      isotachophoresis (ITP) preconcentration and zone electrophoresis (ZE) separation
      may provide great advantages for sensitive, rapid and cost-effective clinical
      analysis. In this study, an HBV genotyping method with only one amplification
      round was developed by the application of the ITP-ZE chip. All the analysis steps
      of the ITP-ZE separation including sample injection, stacking and separation were
      performed continuously, controlled by sequential high-voltage switching. A 2.1cm
      sample plug was preconcentrated between discontinuous buffers in ITP process,
      followed by ZE separation. Sensitivity enhancement was obtained through the
      increase of sample loading volume. The average LOD value of the ITP-ZE
      microfluidic chip was determined to be 0.0021pg/muL. In a large-scale HBV
      genotyping test, single round PCR products were analyzed by ITP-ZE microfluidic
      chip, and the results were compared with that of the conventional method. Among
      the 200 cases studied, the classification rate obtained with microfluidic chip
      was 93%, which was 6% higher than that obtained with the conventional method.
      Method with ITP-ZE chip analysis provides HBV genotyping information in reduced
      PCR amplification time with higher detection rate when compared with conventional
      method. This method holds great potential for extrapolation to the abundance of
      similar molecular biology-based techniques in clinical diagnosis.

PMID- 16899414
TI  - Caloric restriction and intermittent fasting: two potential diets for successful
      brain aging.
AB  - The vulnerability of the nervous system to advancing age is all too often
      manifest in neurodegenerative disorders such as Alzheimer's and Parkinson's
      diseases. In this review article we describe evidence suggesting that two dietary
      interventions, caloric restriction (CR) and intermittent fasting (IF), can
      prolong the health-span of the nervous system by impinging upon fundamental
      metabolic and cellular signaling pathways that regulate life-span. CR and IF
      affect energy and oxygen radical metabolism, and cellular stress response
      systems, in ways that protect neurons against genetic and environmental factors
      to which they would otherwise succumb during aging. There are multiple
      interactive pathways and molecular mechanisms by which CR and IF benefit neurons
      including those involving insulin-like signaling, FoxO transcription factors,
      sirtuins and peroxisome proliferator-activated receptors. These pathways
      stimulate the production of protein chaperones, neurotrophic factors and
      antioxidant enzymes, all of which help cells cope with stress and resist disease.
      A better understanding of the impact of CR and IF on the aging nervous system
      will likely lead to novel approaches for preventing and treating
      neurodegenerative disorders.

PMID- 16899418
TI  - Human osteosarcoma cell adhesion behaviour on hydroxyapatite integrated chitosan
      poly(acrylic acid) polyelectrolyte complex.
AB  - A novel degradable composite system has been prepared by integrating
      hydroxyapatite, Ca(10)(PO(4))(6)(OH)(2), (HAP) in a polyelectrolyte complex
      matrix of chitosan (CHI) and poly(acrylic acid) (PAA). The composite was
      formulated by integrating 80 wt.% HAP in the polyelectrolyte complex matrix of
      CHI and PAA in the ratio 40/60 (designated as CPH). The composite could be easily
      fabricated into clinically significant shapes by a simple moulding procedure
      intended for bone graft applications. The adhesion behaviour of human
      osteosarcoma (HOS) cells on this degradable composite system was studied by
      selecting the polyelectrolyte complex, CHI/PAA 40/60 (designated as CP) as
      control sample. Light microscopic observations show that cells around CPH
      retained the typical morphology of HOS cells while cells around the
      polyelectrolyte complex showed a cytotoxic effect. The adhesion behaviour as well
      as morphological responses of the seeded cells was further investigated by
      scanning electron microscopy. The scanning electron micrographs of the
      polyelectrolyte complex, CP, showed the presence of rounded cells with raised
      nuclear regions, indicating delayed spreading; cells adhered on CPH were
      flattened with filopodia and showed good attachment and spreading, indicating
      better adhesion onto the HAP integrated composite. Comparing the MTT assay for
      quantitative evaluation of cell viability, CPH showed a higher percentage of
      metabolically active cells compared to CP.

PMID- 16899417
TI  - Development and validation of a selective and robust LC-MS/MS method for high
      throughput quantifying rizatriptan in small plasma samples: application to a
      clinical pharmacokinetic study.
AB  - An analytical method based on liquid chromatography with positive ion
      electrospray ionization (ESI) coupled to tandem mass spectrometry detection (LC
      MS/MS) was developed for the determination of a potent 5-HT(1B/1D) receptor
      agonist, rizatriptan in human plasma using granisetron as the internal standard.
      The analyte and internal standard were isolated from 100 microL plasma samples by
      liquid-liquid extraction (LLE) and chromatographed on a Lichrospher C18 column
      (4.6mm x 50mm, 5 microm) with a mobile phase consisting of acetonitrile-10mM
      aqueous ammonium acetate-acetic acid (50:50:0.5, v/v/v) pumped at 1.0 mL/min. The
      method had a chromatographic total run time of 2 min. A Varian 1200 L
      electrospray tandem mass spectrometer equipped with an electrospray ionization
      source was operated in selected reaction monitoring (SRM) mode with the precursor
      to-product ion transitions m/z 270-->201 (rizatriptan) and 313.4-->138
      (granisetron) used for quantitation. The assay was validated over the
      concentration range of 0.05-50 ng/mL and was found to have acceptable accuracy,
      precision, linearity, and selectivity. The mean extraction recovery from spiked
      plasma samples was above 98%. The intra-day accuracy of the assay was within 12%
      of nominal and intra-day precision was better than 13% C.V. Following a 10mg dose
      of the compound administered to human subjects, mean concentrations of
      rizatriptan ranged from 0.2 to 70.6 ng/mL in plasma samples collected up to 24h
      after dosing. Inter-day accuracy and precision results for quality control
      samples run over a 5-day period alongside clinical samples showed mean accuracies
      of within 12% of nominal and precision better than 9.5% C.V.

PMID- 16899419
TI  - Intraoperative coronary graft flow determination--does it have a prognostic value
      for midterm graft patency?
AB  - OBJECTIVE: To characterise the prognostic value of intraoperative ultrasonic
      graft flow determination during CABG for mid-term patency. METHODS: From 01/2000
      to 08/2003 3146 CABG procedures were performed at our institution. Graft flow was
      determined in all patients. Lumen diameter was given in mm and a sclerosis score
      was applied for the target vessel. 100 of these patients (3.2%) underwent
      postoperative coronary angiography at a mean time interval of 8.0 +/- 0.5 months.
      RESULTS: In 100 patients, 114 LITA and 204 venous anastomoses were performed. At
      re-angiography 112 LITA (98%) and 174 venous (85%) anastomoses were patent. The
      amount of occluded LITA grafts was to low to perform statistical analyses. Mean
      graft flow of patent vein grafts was 48 +/- 2 ml/min vs. 32 +/- 4 ml/min in
      occluded vein grafts (p = 0.001). After multiple logistic regression analysis,
      only intraoperative vein graft flow was found to be a predictor for patency at
      mid-term (p = 0.005, odds ratio 0.97, 95% confidence interval (CI) from 0.95
      0.99). No differences were found concerning sclerosis scores or vessel lumen
      between patent and occluded grafts. CONCLUSIONS: Significant differences
      concerning intraoperative graft flow were found between vein grafts patent or
      occluded at re-angiography. The predictive power of intraoperative vein graft
      flow for mid-term patency was confirmed by multiple logistic regression analysis.

PMID- 16899420
TI  - Structured treatment interruptions following immediate initiation of HAART in
      eight patients with acute HIV-1 seroconversion.
AB  - BACKGROUND: The immunological and clinical benefits of structured treatment
      interruptions (STIs) during primary HIV-1 infection remain largely unclear.
      PATIENTS AND METHODS: Eight patients identified during primary HIV-1 infection
      were immediately treated with HAART and underwent subsequent STIs after reaching
      complete viral suppression of HIV-RNA in peripheral plasma. HAART was re
      initiated if either HIV-1 RNA >5000 copies/ml, CD4-cells <200 cells/microl or
      symptomatic HIV-1 disease was observed. RESULTS: After treatment discontinuation,
      four of eight patients were able to persistently control HIV-1 viremia below 5000
      copies/ml until the last time point of follow-up (median 3 years). CD4-cell
      counts were within the interquartile range of untreated individuals compared to
      historical reference data from the MACS cohort. In the remaining study subjects
      persistent virological control was not reached despite repeated STIs. Moreover,
      compared to the MACS cohort repetitive virological failures during STIs appeared
      to induce an accelerated decline of CD4-cells. CONCLUSION: Spontaneous HIV-1
      control after treated primary HIV-1 infection was possible in four out of eight
      individuals, however, if STIs after treated primary infection ameliorate the
      overall HIV-1 disease progression remains unknown. In the absence of viral
      control, repetitive viral exposure during STIs might be associated with
      accelerated decline of CD4-cell counts.

PMID- 16899421
TI  - Early diagnosis of colorectal cancer: a preventive task in occupational health.
AB  - Morbidity of colorectal cancer is still accreting; therefore in 2003 a total of
      57000 patients fell ill and about 28000 died due to colorectal carcinoma.
      According to the etiology, many different factors are currently in discussion.
      However, as in about 25-30% of the cases familial clustering can be observed one
      of the most probable might be the genetic predisposition. Nevertheless only in 3%
      of all cases this predisposition is also scientifically assured. The high average
      age of manifestation raised the question if there might be also an occupational
      relationship for colorectal carcinoma in tense of an occupational disease.
      Therefore there is sight for occupational health to contribute to early diagnosis
      of colorectal carcinoma within the scope of routine check-up, health management
      and research of occupational diseases.

PMID- 16899422
TI  - A complex interferon inducer potentiates the functional macrophage activity
      during Staphylococcal infection.
AB  - The antibacterial effect of a new type I interferon inducer, an yeast RNA
      tilorone molecular complex (MC), was studied using a model of staphylococcal
      infection. The MC taken in experimental doses being optimal interferon-inducing
      ones accelerates the Staphylococcus aureus elimination from mice organisms
      accompanied by increased functional ability (phagocytosis and bactericide
      activity) of peritoneal macrophages. The conclusion is that the MC antibacterial
      activity detected is mediated by its interferon-inducing properties.

PMID- 16899423
TI  - Occasional urinary tract infections and urinary depletion effect mask RTA and
      carbonate-apatite formation in a strong urinary stone former.
AB  - We report on a female patient with severe bilateral urolithiasis. A once-off
      stone analysis performed in the past revealed Mg-phosphate. Occasional UTIs were
      considered to be the sole cause of stone formation. To date, this assumption had
      not been checked thoroughly, while stone formation in the patient steadily
      increased. An inpatient metabolic and analytical work up was performed and stone
      growth related urinary alteration was taken into account in urinalysis
      interpretation. No UTI. NH4Cl-loading test indicated RTA. CT revealed calculi in
      both kidneys. Carbonate-apatite (CAP) dominates stone composition. Computed
      urinary composition proximal to stones indicates hypercalciuria. In this patient,
      occasional UTIs (pH) masked the causes of urolithiasis. Lack of updated stone
      analysis (CAP), metabolic work up (RTA) and improved urinalysis interpretation
      (hypercalciuria) concealed the true causes of stone formation.

PMID- 16899425
TI  - Treatment of therapy-resistant Alopecia areata with fumaric acid esters.
AB  - BACKGROUND: Alopecia areata is a cosmetically very disfiguring clinical picture
      and can be a great emotional burden to the patient, especially when persisting
      for a longer period of time. PATIENTS AND METHODS: 10 patients with an alopecia
      resistant to therapy were treated within the bounds of an open, non-placebo
      controlled pilot study with fumaric acid esters (FAE's, Fumaderm) for a period of
      six months and a maximum dose of 120 mg dimethylfumarate per day. The shortest
      space of time between persistent Alopecia areata and the start of the therapy
      with FAE was between six months and 17 years. RESULTS: Six patients took benefit
      from the six months therapy with FAE. In three of them very good results could be
      observed, presenting an almost entire remission, one patient showed a good
      success with a focal remission. With two patients a mediocre to moderate outcome
      was observed with growth of partly diffuse spread or very thin hair. Four
      patients took no benefit from the FAE therapy at all. CONCLUSIONS: FAE can be
      useful in the treatment of therapy-resistant Alopecia areata. This therapy
      approach should be validated in a multi-centre study.

PMID- 16899424
TI  - Effects of Iloprost and pentoxifylline on renal ischemia-reperfusion in rabbit
      model.
AB  - OBJECTIVE: In ischemia-reperfusion, Iloprost decreases neutrophil activation and
      aggregation besides inhibition of oxygen-free radical production. Pentoxifylline
      (Ptx) attenuates reperfusion-associated membrane injury and tissue edema,
      suppresses leukocyte adhesion and improves hindlimb blood flow during the
      reperfusion period. The primary hypothesis in this study was that Iloprost could
      present better protection than pentoxyfillin on renal ischemia-reperfusion in
      rabbit model. MATERIALS AND METHODS: Forty rabbits were grouped into four.
      Iloprost was continuously infused starting half an hour before the reperfusion
      after 2 hours ischemia and during the 4 hours reperfusion period in Group 1
      whereas the Group 2 was treated with pentoxyfillin. Group 3 was the control group
      which didn't receive any medication. Forth group was sham group. Renal tissues
      were histologically and biochemically evaluated. RESULTS: The histologic scores
      were obtained according to presence of tubuler necrosis and atrophy, regenerative
      atypia, hydropic degeneration (Group 1 vs Group 3; p<0.001, Group 2 vs Group 3; p
      = 0.001, Group 1 vs Group 2; p = 0.331). Malondialdehyde levels of the medicated
      groups were 109 +/- 11 nmol/gr tissue in Group 1, 119 +/- 15 nmol / gr tissue in
      Group 2 and 132 +/- 14 nmol / gr tissue in Group 3 (Group 1 vs Group 2; p =
      0.130, Group 1 vs Group 3, p = 0.002, Group 2 vs Group 3; p = 0.045).
      Malondialdehyde levels and histologic scores of all of the groups were
      significantly different from the sham group. CONCLUSION: Iloprost and
      pentoxyfillin reduced renal ischemia-reperfusion injury in rabbit model. There
      was not a significant difference between these two medications.

PMID- 16899426
TI  - Fabry disease in a female patient due to a de novo point mutation at position 691
      of exon 5.
AB  - Fabry disease is an X-linked lysosomal disorder caused by deficiency of the
      lysosomal enzyme alpha-galactosidase A. We report on a 32-year-old female patient
      with an 8-year history of vascular lesions on the hips and periumbilical region
      and a presumed Fabry disease without positive family history. Ophthalmologic
      evaluation revealed whorl-like corneal opacities. Echocardiography revealed
      myxomatous degeneration and prolapse of the mitral valve. DNA analysis of the
      alpha-galactosidase A gene confirmed the diagnosis of Fabry disease, showing a de
      novo point mutation at position 691 of exon 5. The patient is now obtaining
      intravenous enzyme replacement therapy with agalsidase alfa and remains without
      drug-related reactions.

PMID- 16899427
TI  - Steroid refractory episcleritis as early manifestation of neurosyphilis.
AB  - Since the incidence of syphilis is constantly rising in western countries during
      the last few years the awareness of atypical presentations of this treatable
      disease is warranted. Especially since early treatment results in complete
      elimination of Treponema pallidum, thus preventing disabilities and neurological
      deterioration as a consequence of late stage infection. We describe a case in
      which a patient with asymptomatic neurosyphilis presented with a history of
      longstanding episcleritis. The patient was first seen in an outpatient setting,
      where the resistance of ocular inflammation to steroid treatment led to the
      uncommon diagnosis. Prolonged antibiotic treatment resulted in a complete
      solution of all clinical findings and a decrease of specific treponemal antibody
      titers. This case might serve as an example that with the recent increase in
      sexual transmitted diseases practitioners might be more often confronted with
      uncommon presentations of syphilis.

PMID- 16899437
TI  - Cardiovascular health and the menopause - an approach for gynecologists: an
      overview.

PMID- 16899438
TI  - Cardiovascular health and the menopause: the gynecologist as the patients'
      interface.
AB  - The large decrease in estrogen following menopause appears to explain the
      dramatic increase in cardiovascular disease (CVD) in postmenopausal women.
      Gynecologists are well placed to play a primary role in the diagnosis, prevention
      and management of CVD in these patients; this role may include advice on
      lifestyle changes, and, if appropriate, prescribing preventative treatments such
      as hormone replacement therapy (HRT) and lipid-lowering drugs. The use of
      estrogen replacement therapy (ERT) to prevent CVD is supported by a number of
      observational studies. However, recently, large, randomized trials gave
      unexpected, conflicting data on the cardiovascular benefits of HRT, leading to
      confusion, and influencing both patient and clinical perceptions regarding the
      role of HRT postmenopause. These different outcomes may be due to differences in
      the HRT regimens, mean age and mean time from menopause at enrollment, duration
      of therapy, and patient selection bias in observational studies. A 'unified
      hypothesis' consistent with findings from all studies has now been developed: HRT
      initiated at the time of the menopause prevents CVD, whereas HRT initiated years
      after the menopause seems to increase CHD events. This knowledge is essential for
      gynecologists making clinical decisions regarding HRT use.

PMID- 16899439
TI  - Why is cardiovascular health important in menopausal women?
AB  - Since endogenous estrogen shows some preventative benefits against cardiovascular
      risk factors in premenopausal women, cardiovascular disease (CVD) is often
      considered a male disease. However, CVD is the biggest cause of death in women,
      especially after menopause when endogenous estrogen withdrawal has detrimental
      effects on cardiovascular physiology and whole-body metabolism. Despite this,
      awareness of the risk of CVD is low in both women and in doctors; this needs
      rectifying. Women are under-represented in most clinical studies of CVD.
      Following diagnosis of CVD, the prognosis for women is not systematically similar
      to that for men. Furthermore, from the few comparisons conducted, gender
      differences in response to pharmacological interventions are evident, so that
      results obtained in wholly or largely male-based studies cannot be systematically
      extrapolated to women. Women with CVD should be afforded equivalent
      investigations and treatment to men, and it is vital that women be included in
      clinical trials in sufficient numbers to allow sub-group analyses and subsequent
      development of appropriate therapies. Since CVD is usually advanced by the time
      symptoms appear, prevention is the key; health management advice might include
      smoking cessation, adoption of a healthy diet, and incorporation of physical
      activity into the lifestyle.

PMID- 16899440
TI  - Managing cardiovascular risk in menopausal women.
AB  - Blood pressure control and prevention of glucose intolerance are primary factors
      in overcoming the increased cardiovascular risks in menopausal women. This
      heightened risk may partially be explained by the metabolic syndrome - a
      precursor of type 2 diabetes - in which the renin-angiotensin-aldosterone system
      may play a pivotal role. Once diabetes occurs, the cardiovascular risk is
      considerably greater in postmenopausal women than in men - especially if
      hypertension is also present. An additional risk factor, weight gain, is common
      in postmenopausal women not treated with hormone replacement therapy. Rigorous
      control of blood pressure has been shown to be particularly beneficial in women
      with metabolic syndrome; a reduction in blood pressure can reduce the mortality
      rate of ischemic stroke. The administration of hormone replacement therapy can
      also reduce the likelihood of coronary heart disease in postmenopausal women;
      therefore therapy should be started early in the menopausal transition to
      maximize cardiovascular protection. As such, an ideal hormone replacement therapy
      that can overcome hypertension, prevent body weight gain and control serum
      triglycerides offers an important advance in cardiovascular risk management
      during the menopause.

PMID- 16899445
TI  - The effect of an HIV/AIDS educational program on the knowledge, attitudes, and
      behaviors of dental professionals.
AB  - The Pacific AIDS Education and Training Center (PAETC) developed and tested over
      time a curriculum to meet the changed HIV/AIDS-related needs of dental health
      professionals. The objective of this study was to evaluate the HIV-related
      knowledge, attitudes/beliefs, and behaviors among the participants of a CE
      training course based on this curriculum, both before and six weeks after the
      completion of the course. The project recruited 106 participants who were dental
      health professionals over a ten and a half year period (1992-2003). The dental
      participants consisted of 79 percent dentists and 21 percent dental hygienists or
      dental assistants. The sample was 67 percent male, 33 percent female, 45 percent
      Caucasian, and 24 percent Asian. An adapted questionnaire was used before and
      after the training to assess the educational needs of the participants and
      evaluate the success of the program in meeting those needs. Approximately 81
      percent of the participants completed both questionnaires. After the course, the
      participants significantly changed their knowledge, attitudes/beliefs, and
      behaviors (65 percent, 86 percent, 55 percent respectively, all at p=.0001).
      Overall, the educational program was successful in increasing and promoting the
      HIV/AIDS-related knowledge and attitudes/beliefs of the participants and
      enhancing their commitment to infection control and HIV risk screening behaviors.

PMID- 16899446
TI  - Complexed crystal structure of replication restart primosome protein PriB reveals
      a novel single-stranded DNA-binding mode.
AB  - PriB is a primosomal protein required for replication restart in Escherichia
      coli. PriB stimulates PriA helicase activity via interaction with single-stranded
      DNA (ssDNA), but the molecular details of this interaction remain unclear. Here,
      we report the crystal structure of PriB complexed with a 15 bases oligonucleotide
      (dT15) at 2.7 A resolution. PriB shares structural similarity with the E.coli
      ssDNA-binding protein (EcoSSB). However, the structure of the PriB-dT15 complex
      reveals that PriB binds ssDNA differently. Results from filter-binding assays
      show that PriB-ssDNA interaction is salt-sensitive and cooperative. Mutational
      analysis suggests that the loop L45 plays an important role in ssDNA binding.
      Based on the crystal structure and biochemical analyses, we propose a cooperative
      mechanism for the binding of PriB to ssDNA and a model for the assembly of the
      PriA-PriB-ssDNA complex. This report presents the first structure of a
      replication restart primosomal protein complexed with DNA, and a novel model that
      explains the interactions between a dimeric oligonucleotide-binding-fold protein
      and ssDNA.

PMID- 16899448
TI  - Information-theoretic identification of predictive SNPs and supervised
      visualization of genome-wide association studies.
AB  - The size, dimensionality and the limited range of the data values makes
      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 SNP datasets capable of
      identifying informative SNPs in genome-wide association studies. VizStruct is an
      interactive visualization technique that reduces multi-dimensional data to three
      dimensions using a combination of the discrete Fourier transform and the Kullback
      Leibler divergence. The performance of 3D VizStruct was challenged with several
      diverse, biologically relevant published datasets including the human lipoprotein
      lipase (LPL) gene locus, the human Y-chromosome in several populations and a
      multi-locus genotype dataset of coral samples from four populations. In every
      case, the SNPs and or polymorphic markers identified by the 3D VizStruct mapping
      were predictive of the underlying biology.

PMID- 16899447
TI  - Identification of the REST regulon reveals extensive transposable element
      mediated binding site duplication.
AB  - The genome-wide mapping of gene-regulatory motifs remains a major goal that will
      facilitate the modelling of gene-regulatory networks and their evolution. The
      repressor element 1 is a long, conserved transcription factor-binding site which
      recruits the transcriptional repressor REST to numerous neuron-specific target
      genes. REST plays important roles in multiple biological processes and disease
      states. To map RE1 sites and target genes, we created a position specific scoring
      matrix representing the RE1 and used it to search the human and mouse genomes. We
      identified 1301 and 997 RE1s inhuman and mouse genomes, respectively, of which
      >40% are novel. By employing an ontological analysis we show that REST target
      genes are significantly enriched in a number of functional classes. Taking the
      novel REST target gene CACNA1A as an experimental model, we show that it can be
      regulated by multiple RE1s of different binding affinities, which are only
      partially conserved between human and mouse. A novel BLAST methodology indicated
      that many RE1s belong to closely related families. Most of these sequences are
      associated with transposable elements, leading us to propose that transposon
      mediated duplication and insertion of RE1s has led to the acquisition of novel
      target genes by REST during evolution.

PMID- 16899449
TI  - Two uniquely arranged thyroid hormone response elements in the far upstream 5'
      flanking region confer direct thyroid hormone regulation to the murine
      cholesterol 7alpha hydroxylase gene.
AB  - Cholesterol 7alpha hydroxlyase (CYP7A1) is a key enzyme in cholesterol catabolism
      to bile acids and its activity is important for maintaining appropriate
      cholesterol levels. The murine CYP7A1 gene is highly inducible by thyroid hormone
      in vivo and there is an inverse relationship between thyroid hormone and serum
      cholesterol. Eventhough gene expression has been shown to be upregulated, whether
      the induction was mediated through a direct effect of thyroid hormone on the
      CYP7A1 promoter has never been established. Using gene targeted mice, we show
      that either of the two TR isoforms are sufficient to maintain normal hepatic
      CYP7A1 expression but a loss of both results in a significant decrease in
      expression. We also identified two new functional thyroid hormone receptor
      binding sites in the CYP7A1 5' flanking sequence located 3 kb upstream from the
      transcription start site. One site is a DR-0, which is an unusual type of TR
      response element, and the other consists of only a single recognizable half site
      that is required for TR/retinoid X receptor (RXR) binding. These two independent
      TR-binding sites are closely spaced and both are required for full induction of
      the CYP7A1 promoter by thyroid hormone, although the DR-0 site was more crucial.

PMID- 16899450
TI  - Genotyping and annotation of Affymetrix SNP arrays.
AB  - In this paper we develop a new method for genotyping Affymetrix single nucleotide
      polymorphism (SNP) array. The method is based on (i) using multiple arrays at the
      same time to determine the genotypes and (ii) a model that relates intensities of
      individual SNPs to each other. The latter point allows us to annotate SNPs that
      have poor performance, either because of poor experimental conditions or because
      for one of the alleles the probes do not behave in a dose-response manner.
      Generally, our method agrees well with a method developed by Affymetrix. When
      both methods make a call they agree in 99.25% (using standard settings) of the
      cases, using a sample of 113 Affymetrix 10k SNP arrays. In the majority of cases
      where the two methods disagree, our method makes a genotype call, whereas the
      method by Affymetrix makes a no call, i.e. the genotype of the SNP is not
      determined. By visualization it is indicated that our method is likely to be
      correct in majority of these cases. In addition, we demonstrate that our method
      produces more SNPs that are in concordance with Hardy-Weinberg equilibrium than
      the method by Affymetrix. Finally, we have validated our method on HapMap data
      and shown that the performance of our method is comparable to other methods.

PMID- 16899451
TI  - Identification of small non-coding RNAs from mitochondria and chloroplasts.
AB  - Small non-protein-coding RNAs (ncRNAs) have been identified in a wide spectrum of
      organisms ranging from bacteria to humans. In eukarya, systematic searches for
      ncRNAs have so far been restricted to the nuclear or cytosolic compartments of
      cells. Whether or not small stable non-coding RNA species also exist in cell
      organelles, in addition to tRNAs or ribosomal RNAs, is unknown. We have thus
      generated cDNA libraries from size-selected mammalian mitochondrial RNA and plant
      chloroplast RNA and searched for small ncRNA species in these two types of DNA
      containing cell organelles. In total, we have identified 18 novel candidates for
      organellar ncRNAs in these two cellular compartments and confirmed expression of
      six of them by northern blot analysis or RNase A protection assays. Most
      candidate ncRNA genes map to intergenic regions of the organellar genomes. As
      found previously in bacteria, the presumptive ancestors of present-day
      chloroplasts and mitochondria, we also observed examples of antisense ncRNAs that
      potentially could target organelle-encoded mRNAs. The structural features of the
      identified ncRNAs as well as their possible cellular functions are discussed. The
      absence from our libraries of abundant small RNA species that are not encoded by
      the organellar genomes suggests that the import of RNAs into cell organelles is
      of very limited significance or does not occur at all.

PMID- 16899453
TI  - Structure of Francisella tularensis AcpA: prototype of a unique superfamily of
      acid phosphatases and phospholipases C.
AB  - AcpA is a respiratory burst-inhibiting acid phosphatase from the Centers for
      Disease Control and Prevention Category A bioterrorism agent Francisella
      tularensis and prototype of a superfamily of acid phosphatases and phospholipases
      C. We report the 1.75-A resolution crystal structure of AcpA complexed with the
      inhibitor orthovanadate, which is the first structure of any F. tularensis
      protein and the first for any member of this superfamily. The core domain is a
      twisted 8-stranded beta-sheet flanked by three alpha-helices on either side, with
      the active site located above the carboxyl-terminal edge of the beta-sheet. This
      architecture is unique among acid phosphatases and resembles that of alkaline
      phosphatase. Unexpectedly, the active site features a serine nucleophile and
      metal ion with octahedral coordination. Structure-based sequence analysis of the
      AcpA superfamily predicts that the hydroxyl nucleophile and metal center are also
      present in AcpA-like phospholipases C. These results imply a phospholipase C
      catalytic mechanism that is radically different from that of zinc
      metallophospholipases.

PMID- 16899452
TI  - Induction of single chain tetracycline repressor requires the binding of two
      inducers.
AB  - In this article we report the in vivo and in vitro characterization of single
      chain tetracycline repressor (scTetR) variants in Escherichia coli. ScTetR is
      genetically and proteolytically stable and exhibits the same regulatory
      properties as dimeric TetR in E.coli. Urea-dependent denaturation of scTetR is
      independent of the protein concentration and follows the two-state model with a
      monophasic transition. Contrary to dimeric TetR, scTetR allows the construction
      of scTetR mutants, in which one subunit contains a defective inducer binding site
      while the other is functional. We have used this approach to establish that
      scTetR needs occupation of both inducer binding sites for in vivo and in vitro
      induction. Single mutations causing loss of induction in dimeric TetR lead to non
      inducible scTetR when inserted into one half-side. The construction of scTetR
      H64K S135L S138I (scTetR(i2)) in which one half-side is specific for 4
      dedimethylamino-anhydrotetracycline (4-ddma-atc) and the other for tetracycline
      (tc) leads to a protein which is only inducible by the mixture of tc and 4-ddma
      atc. Fluorescence titration of scTetR(i2) with both inducers revealed distinct
      occupancy with each of these inducers yielding roughly a 1:1 stoichiometry of
      each inducer per scTetR(i2). The properties of this gain of function mutant
      clearly demonstrate that scTetR requires the binding of two inducers for
      induction of transcription.

PMID- 16899455
TI  - Fucosylation of N-glycans regulates the secretion of hepatic glycoproteins into
      bile ducts.
AB  - Fucosylated alpha-fetoprotein (AFP) is a highly specific tumor marker for
      hepatocellular carcinoma (HCC). However, the molecular mechanism by which serum
      level of fucosylated AFP increases in patients with HCC remains largely unknown.
      Here, we report that the fucosylation of glycoproteins could be a possible signal
      for secretion into bile ducts in the liver. We compared oligosaccharide
      structures on glycoproteins in human bile with those in serum by several types of
      lectin blot analyses. Enhanced binding of biliary glycoproteins to lectins that
      recognize a fucose residue was observed over a wide range of molecular weights
      compared with serum glycoproteins. A structural analysis of oligosaccharides by
      two-dimensional mapping high performance liquid chromatography and matrix
      assisted laser desorption ionization time-of flight mass spectrometry confirmed
      the increases in the fucosylation of biliary glycoproteins. Purification followed
      by structural analysis on alpha1-antitrypsin, alpha1-acid glycoprotein and
      haptoglobin, which are synthesized in the liver, showed higher fucosylation in
      bile than in serum. To find direct evidence for fucosylation and sorting signal
      into bile ducts, we used alpha1-6 fucosyltransferase (Fut8)-deficient mice
      because fucosylation of glycoproteins produced in mouse liver was mainly an
      alpha1-6 linkage. Interestingly, the levels of alpha1-antitrypsin and alpha1-acid
      glycoprotein were quite low in bile of Fut8-deficient mice as compared with wild
      type mice. An immunohistochemical study showed dramatic changes in the
      localization of these glycoproteins in the liver of Fut8-deficient mice. Taken
      together, these results suggest that fucosylation is a possible signal for the
      secretion of glycoproteins into bile ducts in the liver. A disruption in this
      system might involve an increase in fucosylated AFP in the serum of patients with
      HCC.

PMID- 16899454
TI  - Mutant analysis of the Shal (Kv4) voltage-gated fast transient K+ channel in
      Caenorhabditis elegans.
AB  - Shal (Kv4) alpha-subunits are the most conserved among the family of voltage
      gated potassium channels. Previous work has shown that the Shal potassium channel
      subfamily underlies the predominant fast transient outward current in Drosophila
      neurons (Tsunoda, S., and Salkoff, L. (1995) J. Neurosci. 15, 1741-1754) and the
      fast transient outward current in mouse heart muscle (Guo, W., Jung, W. E.,
      Marionneau, C., Aimond, F., Xu, H., Yamada, K. A., Schwarz, T. L., Demolombe, S.,
      and Nerbonne, J. M. (2005) Circ. Res. 97, 1342-1350). We show that Shal channels
      also play a role as the predominant transient outward current in Caenorhabditis
      elegans muscle. Green fluorescent protein promoter experiments also revealed SHL
      1 expression in a subset of neurons as well as in C. elegans body wall muscle and
      in male-specific diagonal muscles. The shl-1 (ok1168) null mutant removed all
      fast transient outward current from muscle cells. SHL-1 currents strongly
      resembled Shal currents in other species except that they were active in a more
      depolarized voltage range. We also determined that the remaining delayed
      rectifier current in cultured myocytes was carried by the Shaker ortholog SHK-1.
      In shl-1 (ok1168) mutants there was a significant compensatory increase in the
      SHK-1 current. Male shl-1 (ok1168) animals exhibited reduced mating efficiency
      resulting from an apparent difficulty in locating the hermaphrodite vulva. SHL-1
      channels are apparently important in fine-tuning complex behaviors, such as
      mating, that play a crucial role in the survival and propagation of the species.

PMID- 16899457
TI  - Intra- or intercomplex binding to the gamma-secretase enzyme. A model to
      differentiate inhibitor classes.
AB  - Gamma-secretase is one of the critical enzymes required for the generation of
      amyloid-beta peptides from the beta-amyloid precursor protein. Because amyloid
      beta peptides are generally accepted to play a key role in Alzheimer disease,
      gamma-secretase inhibition holds the promise for a disease-modifying therapy for
      this neurodegenerative condition. Although recent progress has enhanced the
      understanding of the biology and composition of the gamma-secretase enzyme
      complex, less information is available on the actual interaction of various
      inhibitor classes with the enzyme. Here we show that the two principal classes of
      inhibitor described in the scientific and patent literature, aspartyl protease
      transition state analogue and small molecule non-transition state inhibitors,
      display fundamental differences in the way they interact with the enzyme. Taking
      advantage of a gamma-secretase enzyme overexpressing cellular system and
      different radiolabeled gamma-secretase inhibitors, we observed that the maximal
      binding of non-transition state gamma-secretase inhibitors accounts only for half
      the number of catalytic sites of the recombinant enzyme complex. This
      characteristic stoichiometry can be best accommodated with a model whereby the
      non-transition state inhibitors bind to a unique site at the interface of a
      dimeric enzyme. Subsequent competition studies confirm that this site appears to
      be targeted by the main classes of small molecule gamma-secretase inhibitor. In
      contrast, the non-steroidal anti-inflammatory drug gamma-secretase modulator
      sulindac sulfide displayed noncompetitive antagonism for all types of inhibitor.
      This finding suggests that non-steroidal anti-inflammatory drug-type gamma
      secretase modulators target an alternative site on the enzyme, thereby changing
      the conformation of the binding sites for gamma-secretase inhibitors.

PMID- 16899456
TI  - Bisandrographolide from Andrographis paniculata activates TRPV4 channels.
AB  - Many transient receptor potential (TRP) channels are activated or blocked by
      various compounds found in plants; two prominent examples include the activation
      of TRPV1 channels by capsaicin and the activation of TRPM8 channels by menthol.
      We sought to identify additional plant compounds that are active on other types
      of TRP channels. We screened a library of extracts from 50 Chinese herbal plants
      using a calcium-imaging assay to find compounds active on TRPV3 and TRPV4
      channels. An extract from the plant Andrographis paniculata potently activated
      TRPV4 channels. The extract was fractionated further, and the active compound was
      identified as bisandrographolide A (BAA). We used purified compound to
      characterize the activity of BAA on certain TRPV channel subtypes. Although BAA
      activated TRPV4 channels with an EC(50) of 790-950 nm, it did not activate or
      block activation of TRPV1, TRPV2, or TRPV3 channels. BAA activated a large TRPV4
      like current in immortalized mouse keratinocytes (308 cells) that have been shown
      to express TRPV4 protein endogenously. This compound also activated TRPV4
      currents in cell-free outside-out patches from HEK293T cells overexpressing TRPV4
      cDNA, suggesting that BAA can activate the channel in a membrane-delimited
      manner. Another related compound, andrographolide, found in abundance in the
      plant Andrographis was unable to activate or block activation of TRPV4 channels.
      These experiments show that BAA activates TRPV4 channels, and we discuss the
      possibility that activation of TRPV4 by BAA could play a role in some of the
      effects of Andrographis extract described in traditional medicine.

PMID- 16899458
TI  - Significance of ectodomain cysteine boxes 2 and 3 for the activation mechanism of
      the thyroid-stimulating hormone receptor.
AB  - Recently, we identified constitutively activating mutations at positions Asp-403,
      Glu-404, and Asn-406 in the third extracellular cysteine box (C-b3) of the
      thyroid-stimulating hormone receptor. We hypothesized that this region could act
      as a molecular interface between the extracellular and serpentine domain. In this
      study we present a model for properties of potential interaction partners for
      this region. Moreover, we show that Pro-400 and Pro-407 adjacent to this epitope
      are also important for stabilizing the partially active, basal conformation of
      the wild-type (WT) thyroid-stimulating hormone receptor. Furthermore, the
      mutation K291A in the second extracellular cysteine box (C-b2) was identified as
      a new constitutively activating mutation that releases the basal conformation of
      the WT receptor like the known tryptic cleavage in its close vicinity. Taken
      together, we provide an activation scenario at the C-b2/C-b3 unit. Three anchor
      fragments (anchors I-III) most likely constrain the basal conformation. The three
      anchor fragments are tightly packed. A disulfide bridge holds the C-b2/C-b3
      portions in close positions. Independent of the type of conformational
      interference such as side chain modifications, tryptic cleavage, or hormone
      stimulation that act on the constrained C-b2/C-b3 WT conformation, it will always
      release one of the anchor fragments. Subsequently, this results in a
      conformational displacement of the C-b2/C-b3 portions relative to each other,
      inducing receptor activation.

PMID- 16899459
TI  - C-terminal truncation impairs glycosylation of transmembrane collagen XVII and
      leads to intracellular accumulation.
AB  - Collagen XVII, a type II transmembrane protein in hemidesmosomes, is involved in
      the anchorage of stratified epithelia to the underlying mesenchyme. Its functions
      are regulated by ectodomain shedding, and its genetic defects lead to epidermal
      detachment in junctional epidermolysis bullosa (JEB), a heritable skin fragility
      syndrome, but the molecular disease mechanisms remain elusive. Here we used a
      spontaneously occurring homozygous COL17A1 deletion mutant in JEB to discern
      glycosylation of collagen XVII. The mutation truncated the distal ectodomain and
      positioned the only N-glycosylation site 34 amino acids from the newly formed C
      terminus, which impaired efficient N-glycosylation. Immunofluorescence staining
      of authentic JEB keratinocytes and of COS-7 cells transfected with the mutant
      indicated intracellular accumulation of collagen XVII precursor molecules. Cell
      surface biotinylation and quantification of ectodomain shedding demonstrated that
      only about 15% of the truncated collagen XVII reached the cell surface. The cell
      surface-associated molecules were N-glycosylated in a normal manner, in contrast
      to the molecules retained within the cells, indicating that N-glycosylation of
      the ectodomain is required for targeting of collagen XVII to the plasma membrane
      and that reduced accessibility of the N-glycosylation site negatively regulates
      this process. Functional consequences of the strong reduction of collagen XVII on
      the cell surface included scattered deposition of cell adhesion molecule laminin
      5 into the extracellular environment and, as a consequence of faulty collagen
      XVII-laminin ligand interactions, aberrant motility of the mutant cells.

PMID- 16899460
TI  - Purification, kinetic characterization, and molecular cloning of a novel enzyme,
      ecdysteroid 22-kinase.
AB  - This is the first report succeeding in the isolation and characterization of an
      enzyme and its gene involved in the phosphorylation of a steroid hormone. It has
      been demonstrated that ecdysteroid 22-phosphates in insect ovaries, which are
      physiologically inactive, serve as a "reservoir" that supplies active free
      ecdysteroids during early embryonic development and that their dephosphorylation
      is catalyzed by a specific enzyme, ecdysteroid-phosphate phosphatase (Yamada, R.,
      and Sonobe, H. (2003), J. Biol. Chem. 278, 26365-26373). In this study,
      ecdysteroid 22-kinase (EcKinase) was purified from the cytosol of the silkworm
      Bombyx mori ovaries to about 1,800-fold homogeneity in six steps of column
      chromatography and biochemically characterized. Results obtained indicated that
      the reciprocal conversion of free ecdysteroids and ecdysteroid 22-phosphates by
      two enzymes, EcKinase and ecdysteroid-phosphate phosphatase, plays an important
      role in ecdysteroid economy of the ovary-egg system of B. mori. On the basis of
      the partial amino acid sequence obtained from purified EcKinase, the nucleotide
      sequence of the cDNA encoding EcKinase was determined. The full-length cDNA of
      EcKinase was composed of 1,850 bp with an open reading frame encoding a protein
      of 386 amino acid residues. The cloned cDNA was confirmed to encode the
      functional EcKinase using the transformant harboring the open reading frame of
      EcKinase. A data base search showed that EcKinase has an amino acid sequence
      characteristic of phosphotransferases, in that it harbors Brenner's motif and
      putative ATP binding sites, but there are no functional proteins that share high
      identity with the amino acid sequence of EcKinase.

PMID- 16899461
TI  - Transition state of the sulfuryl transfer reaction of estrogen sulfotransferase.
AB  - Kinetic isotope effects have been measured for the estrogen sulfotransferase
      catalyzed sulfuryl (SO3) transfer from p-nitrophenyl sulfate to the 5'-phosphoryl
      group of 3'-phosphoadenosine 5'-phosphate. 18(V/K)nonbridge = 1.0016 +/- 0.0005,
      18(V/K)bridge = 1.0280 +/- 0.0006, and 15(V/K) = 1.0014 +/- 0.0004. (15(V/K)
      refers to the nitro group in p-nitrophenyl sulfate). The kinetic isotope effects
      indicate substantial S O bond fission in the transition state, with partial
      charge neutralization of the leaving group. The small kinetic isotope effect in
      the nonbridging sulfuryl oxygen atoms suggests no significant change in bond
      orders of these atoms occurs, consistent with modest nucleophilic involvement. A
      comparison of the data for enzymatic and uncatalyzed sulfuryl transfer reactions
      suggests that both proceed through very similar transition states.

PMID- 16899462
TI  - Multiple antigenic mimotopes of HIV carbohydrate antigens: relating structure and
      antigenicity.
AB  - Carbohydrate mimetic peptides are designable, and they can carry T-cell epitopes
      and circumvent tolerance. A mimic-based human immunodeficiency virus (HIV)
      vaccine can be a viable alternative to carbohydrate-based antigens if the
      diversity of epitopes found on gp120 can be recapitulated. To improve existing
      mimics, an attempt was made to study the structural correlates of the observed
      polyspecificity of carbohydrate mimetic peptides based on the Y(P/R)Y motif in
      more detail. A carbohydrate mimetic peptide, D002 (RGGLCYCRYRYCVCVGR), bound a
      number of lectins with different specificities. Although this peptide reacted
      strongly with both lotus and concanavalin A (ConA) lectins, it bound to lotus
      stronger than ConA. By varying the central motif RYRY, five versions were
      produced in multiple antigen peptide format, and their avidity for lotus and ConA
      lectins was tested by surface plasmon resonance. Although the kinetic parameters
      were similar, the version based on the sequence YPYRY had an optimal affinity for
      both lectins as well as improved avidity for wheat germ agglutinin and
      phytohemagglutinin. Thus, as far as lectin specificity is concerned, YPYRY had
      improved multiple antigenic properties. Both RYRY and YPYRY precipitated
      antibodies from human IgG for intravenous use that bound to gp120 in vitro and
      immunoprecipitated gp120 from transfected CHO-PI cells. Thus, Y(P/R)Y motifs
      mimic multiple carbohydrate epitopes, many of which are found on HIV, and
      preimmune human IgG antibodies that bind to HIV carbohydrates cross-react to a
      comparable extent with both RYRY and YPYRY carbohydrate mimetic peptides.

PMID- 16899465
TI  - c-Abl interacts with the WAVE2 signaling complex to induce membrane ruffling and
      cell spreading.
AB  - The Wiskott-Aldrich syndrome-related protein WAVE2 promotes Arp2/3-dependent
      actin polymerization downstream of Rho-GTPase activation. The Abelson-interacting
      protein-1 (Abi-1) forms the core of the WAVE2 complex and is necessary for proper
      stimulation of WAVE2 activity. Here we have shown that the Abl-tyrosine kinase
      interacts with the WAVE2 complex and that Abl kinase activity facilitates
      interaction between Abl and WAVE2 complex members. We have characterized various
      interactions between Abl and members of the WAVE2 complex and revealed that Abi-1
      promotes interaction between Abl and WAVE2 members. We have demonstrated that Abl
      dependent phosphorylation of WAVE2 is necessary for its activation in vivo, which
      is highlighted by the findings that RNA interference of WAVE2 expression in
      Abl/Arg-/- cells has no additive effect on the amount of membrane ruffling.
      Furthermore, Abl phosphorylates WAVE2 on tyrosine 150, and WAVE2-deficient cells
      rescued with a Y150F mutant fail to regain their ability to ruffle and form
      microspikes, unlike cells rescued with wild-type WAVE2. Together, these data show
      that c-Abl activates WAVE2 via tyrosine phosphorylation to promote actin
      remodeling in vivo and that Abi-1 forms the crucial link between these two
      factors.

PMID- 16899463
TI  - Unique biologic properties of recombinant AAV1 transduction in polarized human
      airway epithelia.
AB  - The choice of adeno-associated virus serotypes for clinical applications is
      influenced by the animal model and model system used to evaluate various
      serotypes. In the present study, we sought to compare the biologic properties of
      rAAV2/1, rAAV2/2, and rAAV2/5 transduction in polarized human airway epithelia
      using viruses purified by a newly developed common column chromatography method.
      Results demonstrated that apical transduction of human airway epithelia with
      rAAV2/1 was 100-fold more efficient than rAAV2/2 and rAAV2/5. This transduction
      profile in human airway epithelia (rAAV2/1 >> rAAV2/2 = rAAV2/5) was
      significantly different from that seen following nasal administration of these
      vectors to mouse lung (rAAV2/5 > rAAV2/1 >> rAAV2/2), emphasizing differences in
      transduction of these serotypes between these two species. In stark contrast to
      rAAV2/2 and rAAV2/5, rAAV2/1 transduced both the apical and basolateral membrane
      of human airway epithelia with similar efficiency. However, the overall level of
      transduction across serotypes did not correlate with vector internalization. We
      hypothesized that differences in post-entry processing of these serotypes might
      influence the efficiency of apical transduction. To this end, we tested the
      effectiveness of proteasome inhibitors to augment nuclear translocation and gene
      expression from the three serotypes. Augmentation of rAAV2/1 apical transduction
      of human polarized airway epithelia was 10-fold lower than that for rAAV2/2 and
      rAAV2/5. Cellular fractionation studies demonstrated that proteasome inhibitors
      more significantly enhanced rAAV2/2 and rAAV2/5 translocation to the nucleus than
      rAAV2/1. These results demonstrate that AAV1 transduction biology in human airway
      epithelia differs from that of AAV2 and AAV5 by virtue of altered
      ubiquitin/proteasome sensitivities that influence nuclear translocation.

PMID- 16899464
TI  - Molecular mapping of the chloride-binding site in von Willebrand factor (VWF):
      energetics and conformational effects on the VWF/ADAMTS-13 interaction.
AB  - Physiological concentrations of NaCl inhibit the hydrolysis of von Willebrand
      factor (VWF) by ADAMTS-13. This effect is because of the specific binding of
      chloride ions to VWF. Urea-induced unfolding was measured in the presence of
      NaCl, CH3COONa, and NaClO4 at pH 8.0, 25 degrees C, for multimeric VWF, the
      recombinant A1-A2-A3 VWF domains, and the A1 domain. Chloride stabilizes the
      folded conformation of the A1-A2-A3 and A1 domains more efficiently than acetate
      but less strongly than perchlorate. Spectroscopic evidence showed that chloride
      binds to both the A1 and A1-A2 domain but not to the isolated A2 domain. Binding
      of Cl- to both wild type (WT) and the natural mutant p.R1306W A1-A2-A3 domains of
      VWF has a large heat capacity change equal to -1 and -0.4 kcal mol(-1) K(-1) for
      WT and p.R1306W A1-A2-A3 domains, respectively. This result implies that a burial
      of a vast apolar surface area is caused by conformational transitions linked to
      chloride binding. At any temperature, chloride affinity was higher for WT than
      for the mutant p.R1306W form. Chloride ions inhibit hydrolysis by ADAMTS-13 of
      the A1-A2-A3 and A1-A2 domains in the presence of either urea or high shear
      stress, whereas this effect was either absent or negligible in experiments using
      A2 and A2-A3 domains. These findings show that the A1 domain contains the binding
      site of chloride ions that control allosterically the proteolysis by ADAMTS-13 of
      the Tyr1605-Met1606 bond in the A2 domain and that the R1306W mutation of type 2B
      VWD quenches the binding of chloride ion to the A1 domain.

PMID- 16899466
TI  - Role of protein kinase C-mediated protein phosphorylation in mitochondrial
      translocation of mouse CYP1A1, which contains a non-canonical targeting signal.
AB  - A large number of mitochondrial proteins lack canonical mitochondrial-targeting
      signals. The bimodal transport of cytochromes P450 (CYPs) to endoplasmic
      reticulum and mitochondria (MT), reported previously by us, likely represents one
      mode of non-canonical protein targeting to MT. Herein, we have studied the
      mechanism of mouse MT-CYP1A1 targeting to gain insight into the regulatory
      features and evolutionary conservation of bimodal targeting mechanism. Mouse MT
      CYP1A1 consists of two NH2-terminal-truncated molecular species, +91A1 and
      +331A1. Mutations Pro-2 --> Leu and Tyr-5 --> Leu, which increase the signal
      recognition particle (SRP) binding, diminished MT targeting of the protein in
      intact cells. By contrast, mutations Leu-7 --> Asn and Leu-17 --> Asn, which
      decreased SRP-binding affinity, enhanced MT targeting, thus suggesting that SRP
      binding is an important regulatory step that modulates bimodal targeting. Protein
      kinase C (PKC)-mediated phosphorylation of nascent chains at Thr-35 vastly
      decreased affinity for SRP binding suggesting an important regulatory step. In
      support of these results, COS cell transfection experiments show that
      phosphomimetic mutation Thr-35 --> Asp or induced cellular PKC caused increased
      CYP1A1 targeting to MT and correspondingly lower levels to the endoplasmic
      reticulum. Results suggest evolutionary conservation of chimeric signals and
      bimodal targeting of CYP1A1 in different species. The mouse MT-CYP1A1 is an
      extrinsic membrane protein, which exhibited high FDX1 plus FDXR-mediated N
      demethylation of a number of tricyclic antidepressants, pain killers, anti
      psychotics, and narcotics that are poor substrates for microsomal CYP1A1.

PMID- 16899467
TI  - Changes of aquaporin 5-distribution during release and reaccumulation of
      secretory granules in isoproterenol-treated mouse parotid gland.
AB  - Water channel aquaporin 5 (AQP5) is present in the apical membrane of the
      salivary gland acinar cells. We examined changes of AQP5-distribution during the
      fusion process of secretory granule membranes into the apical membrane and
      subsequent recovery process in the mouse parotid gland by administering
      isoproterenol (IPR) in vivo. We performed immunoperoxidase, immunofluorescence
      and immunoelectron microscopy. In the basal state, AQP5 was localized mainly in
      the apical membrane of the acinar cell. It was also present in the basolateral
      membrane to a lesser extent. When IPR was administered to mice, dot-like, vesicle
      like and vacuole-like labeling for AQP5 was seen in the subapical regions by
      light microscopy. By immunoelectron microscopy, AQP5 was localized at both the
      apical and basolateral plasma membranes in the basal state. At 5 and 30 min after
      the IPR-administration, acinar lumen became enlarged and small invaginations
      formed by fusion of secretory granules were seen. AQP5 was positive along the
      apical plasma membrane and its small invaginations. At 60 min, large
      invaginations of the lumen were formed. AQP5 remained positive in the membrane of
      these large invaginations. At 6 h, large invaginations disappeared and AQP5 was
      localized in the apical plasma membrane. AQP5 was restricted to plasma membranes
      and continuous invaginations formed by the exocytosis of secretory granules. AQP5
      was not detected in the cytoplasm. These observations show that AQP5 does not
      seem to be endocytosed during the membrane recycling process following the
      exocytosis.

PMID- 16899469
TI  - Assessment of gamma dose rates from terrestrial exposure in Serbia and
      Montenegro.
AB  - The gamma dose rates due to naturally occuring terrestrial radionuclides
      ((226)Ra, (232)Th and (40)K) were calculated based on their activities in soil
      samples, determined by gamma-ray spectrometry. A total of 140 soil samples from
      21 different regions of Serbia and Montenegro were collected. The gamma dose
      rates ranged from 7.40 to 29.7 nGy h(-1) for (226)Ra, from 12.9 to 46.5 nGy h(-1)
      for (232)Th and from 12.5 to 37.1 nGy h(-1) for (40)K. The total absorbed gamma
      dose rate due to these radionuclides varied from 34.5 to 97.6 nGy h(-1) with mean
      of 66.8 nGy h(-1). Assuming a 20% occupancy factor, the corresponding annual
      effective dose varied from 4.23 x 10(-5) to 11.9 x 10(-5) Sv with mean of 8.19 x
      10(-5) Sv, i.e. the dose was lower than world wide average value. According to
      the values of external hazard index (mean: 0.39) obtained in this study, the
      radiation hazard was found to be insignificant for population living in the
      investigated area.

PMID- 16899468
TI  - Treatment of long-term intravascular catheter-related bacteraemia with antibiotic
      lock therapy.
AB  - BACKGROUND: Bacteraemia is a major complication associated with the use of long
      term intravascular catheters. Conservative treatment using antibiotic-lock
      therapy (ALT) has been shown to be useful in some studies, but the evidence
      supporting its impact in clinical care is still scarce. METHODS: We evaluated the
      outcome of the episodes of catheter-related bacteraemia (CRB) associated with
      long-term intravascular devices used for chemotherapy or parenteral nutrition and
      that were managed with ALT during a 44 month period in our hospital. Episodes of
      CRB associated with catheters implanted in the same department during the same
      period, and that were managed with only systemic antibiotics were used as a
      control group. Antibiotic-lock solution consisted of a heparin solution of 20
      IU/mL including vancomycin (for Gram-positive microorganisms) or ciprofloxacin or
      gentamicin (for Gram-negative bacilli), all at a concentration of 2 mg/mL. ALT
      was used for a minimum of 8-12 h/day, during 5-14 days. Effectiveness was
      assessed by clinical and microbiological criteria. RESULTS: A total of 801 long
      term intravascular devices were placed in 105 patients during this period. There
      were 127 episodes of bacteraemia documented in these patients, with 92 being CRB.
      Of these, 48 episodes fulfilled inclusion criteria for the analysis. Nineteen
      episodes were treated with ALT plus systemic antibiotics, and 29 episodes were
      treated only with systemic antibiotics. Isolated microorganisms were similar in
      the two groups. The catheter had to be removed during therapy in one episode in
      the antibiotic-lock group and in seven episodes in the control group. Relapse of
      the bacteraemia with the same microorganism after stopping therapy was observed
      in two and three patients in the study group and the control group, respectively.
      Overall, successful treatment was achieved in 84% and 65% of the episodes in the
      antibiotic-lock group and the control group, respectively (P = 0.27).
      CONCLUSIONS: ALT appears as an effective conservative treatment in the management
      of CRB associated with long-term intravascular devices (84% in the present
      series), especially in infections caused by coagulase-negative staphylococci.

PMID- 16899470
TI  - Determination of gamma-emitting radionuclides in the inter-tidal sediments off
      Balochistan (Pakistan) Coast, Arabian Sea.
AB  - Natural radionuclide contents of 226Ra, 228Ra and (40)K were studied for inter
      tidal sediments collected from selected locations off the745 km long Balochistan
      Coast using HPGe detector based gamma-spectrometry system. The sampling zone
      extends from the beaches of Sonmiani (near Karachi metropolis) through Jiwani
      (close to the border of Iran). The natural radioactivity levels detected in
      various sediment samples range from 14.4 +/- 2.5 to 36.6 +/- 3.8 Bq kg(-1) for
      226Ra, 9.8 +/- 1.2 to 35.2 +/- 2.0 Bq kg(-1) for (228)Ra and 144.6 +/- 9.4 to
      610.5 +/- 23.9 Bq kg(-1) for (40)K. No artificial radionuclide was detected in
      any of the marine coastal sediment samples. 137Cs, (60)Co, 106Ru and 144Ce
      contents in sediment samples were below the limit of detection. The measured
      radioactivity levels are compared with those reported in the literature for
      coastal sediments in other parts of the world. The information presented in this
      paper will serve as the first ever local radioactivity database for the
      Balochistan/Makran Coastal belt of Pakistan. The presented data will also
      contribute to the IAEA's, Asia-Pacific Marine Radioactivity Database (ASPAMARD)
      and the Global Marine Radioactivity Database (GLOMARD).

PMID- 16899471
TI  - Polymorphonuclear leucocyte priming in long intermittent nocturnal haemodialysis
      patients--is melatonin a player?
AB  - BACKGROUND: The relationships between sleep quality, melatonin circadian rhythm
      and polymorphonuclear leucocyte (PMNL) priming during the night of dialysis
      treatment compared with a night without dialysis were studied in a group of
      nocturnal haemodialysis (HD) patients. METHODS: Twenty-eight long intermittent
      nocturnal HD patients were included. Sleep quality was assessed by a
      questionnaire and wrist actigraphy. Plasma melatonin levels were assayed every 2
      h, from 9 p.m. to 5 a.m. PMNL priming was assessed by the rate of superoxide
      release from separated PMNLs at 9 p.m. and 5 a.m., on a night of dialysis and a
      night with sleepover in the dialysis unit without being dialysed. RESULTS:
      Melatonin levels increased similarly during a night with and without dialysis,
      reaching peak level at 5 a.m. Most (73%) of the patients had severe sleep
      disturbances. A significant negative correlation was found between the sleep
      quality score, the rate of superoxide release from separated PMNLs and melatonin
      levels. While during a night without dialysis a significant reduction of the rate
      of superoxide release was found at 5 a.m. (compared with 9 p.m.), no significant
      reduction was observed when the patients were dialysed. Patients with flat
      melatonin curves, with <10 pg/ml, showed a faster rate of superoxide release than
      those with higher levels. CONCLUSIONS: The nocturnal HD process does not affect
      plasma melatonin levels or rhythms, suggesting that melatonin is not dialysed.
      Higher endogenous melatonin levels are associated with better sleep and lower
      PMNL priming. The lower PMNL priming in patients with higher plasma melatonin
      levels suggests that melatonin overrides the oxidative burden induced by the
      dialysis process.

PMID- 16899473
TI  - Delayed neointimal healing after drug-eluting stent implantation: seeing is
      believing.

PMID- 16899472
TI  - Relative extents of preformation and neoformation in tree shoots: Analysis by a
      deconvolution method.
AB  - BACKGROUND AND AIMS: Neoformation is the process by which organs not preformed in
      a bud are developed on a growing shoot, generally after preformation extension.
      The study of neoformation in trees has been hindered due to methodological
      reasons. The present report is aimed at assessing the relative importance of
      preformation and neoformation in the development of shoots of woody species.
      METHODS: A deconvolution method was applied to estimate the distribution of the
      number of neoformed organs for eight data sets corresponding to four Nothofagus
      species and a Juglans hybrid. KEY RESULTS: The number of preformed organs was
      higher and less variable than the number of neoformed organs. Neoformation
      contributed more than preformation to explain full-size differences between
      shoots developed in different positions within the architecture of each tree
      species. CONCLUSIONS: Differences between the distributions of the numbers of
      preformed and neoformed organs may be explained by alluding to the duration of
      differentiation and extension for each of these groups of organs. The
      deconvolution of distributions is a useful tool for the analysis of neoformation
      and shoot structure in trees.

PMID- 16899474
TI  - Clinical trials with ST-segment elevation myocardial infarction.

PMID- 16899475
TI  - Randomized trial of effects of continuous combined HRT on markers of lipids and
      coagulation in women with acute coronary syndromes: WHISP Pilot Study.
AB  - AIMS: Randomized trials have not demonstrated coronary heart disease benefit from
      hormone replacement therapy (HRT). We hypothesized that low-dose HRT may avoid
      harm. METHODS AND RESULTS: We studied the effects of HRT on lipids and
      coagulation in women with acute coronary syndromes. A total of 100 post
      menopausal women >55 years were enrolled between 2 and 28 days after an acute
      coronary syndrome and randomized to oral oestradiol-17beta 1 mg plus
      norethisterone acetate 0.5 mg daily, or matching placebo, and followed for up to
      12 months. Levels of lipids, lipoproteins, and haemostasis markers were measured
      at baseline, 3, and 6 months. There were no significant differences in lipid
      levels between the two groups, probably due to concomitant statin use.
      Antithrombin and factor VII levels were significantly lower in the HRT group,
      whereas fibrinogen was significantly decreased in the placebo group. No evidence
      of increased coagulation activation was observed, nor of adverse cardiovascular
      outcomes [odds ratio (OR) 0.63 (95% confidence intervals 0.31-1.31)]. CONCLUSION:
      Low-dose HRT may give cardiovascular benefit. These findings require confirmation
      in a full clinical trial with evaluation of cardiovascular outcomes as the
      primary objective.

PMID- 16899476
TI  - Are manual workers at higher risk of death than non-manual employees when living
      in Swedish municipalities with higher income inequality?
AB  - OBJECTIVES: To test the hypothesis that manual workers are at higher risk of
      death than are non-manual employees when living in municipalities with higher
      income inequality. DESIGN: Hierarchical regression was used for the analysis were
      individuals were nested within municipalities according to the 1990 Swedish
      census. The outcome was all-cause mortality 1992-1998. The income measure at the
      individual level was disposable family income weighted against composition of
      family; the income inequality measure used at the municipality level was the Gini
      coefficient. PARTICIPANTS: The study population consisted of 1 578 186 people
      aged 40-64 years in the 1990 Swedish census, who were being reported as unskilled
      or skilled manual workers, lower-, intermediate-, or high-level non-manual
      employees. RESULTS: There was no significant association between income
      inequality at the municipality level and risk of death, but an expected gradient
      with unskilled manual workers having the highest risk and high-level non-manual
      employees having the lowest. However, in the interaction models the relative risk
      (RR) of death for high-level non-manual employees was decreasing with increasing
      income inequality (RR = 0.77; 95% CI, 0.63-0.93), whereas the corresponding risk
      for unskilled manual workers increased with increasing income inequality (RR =
      1.24; 95% CI, 1.06-1.46). The RRs for skilled manual, low- and medium- level non
      manual employees were not significant. Controlling for income at the individual
      level did not substantially alter these findings, neither did potential
      confounders at the municipality level. CONCLUSIONS: The findings suggest that
      there could be a differential impact from income inequality on risk of death,
      dependent on individuals' social position.

PMID- 16899477
TI  - Identification of differentially expressed proteins in human malignant pleural
      effusions.
AB  - A high protein concentration in a pleural effusion makes it more likely to be a
      malignant than a transudative effusion. However, the variability in protein
      composition between these two forms of pleural effusion is not well understood.
      In order to compare their protein compositions, the proteomic profiles of 14
      malignant and 13 transudative pleural effusions were studied using two
      dimensional gel electrophoresis. Protein spots with differential expression were
      identified by matrix-assisted laser desorption/ionisation quadrupole time-of
      flight mass spectrometry and liquid chromatography/tandem mass spectrometry.
      Targeted proteins were further examined by ELISA and Western immunoassay in all
      samples. Two-dimensional gel electrophoresis revealed seven spots whose
      expression was reduced in malignant pleural effusions. Four of the abnormal spots
      were identified as fibrinogen gamma-chain precursor, two as fibrinogen beta-chain
      precursor and one as pigment epithelium-derived factor. ELISA and Western
      immunoassay showed that pigment epithelium-derived factor levels were
      significantly lower in malignant than in transudative pleural effusions. It has
      been demonstrated that proteomic technologies may help in the elucidation of
      variable expression of proteins with particular functions. By applying these
      technologies, the level of pigment epithelium-derived factor, a potent anti
      angiogenic factor, was found to be significantly lower in malignant than in
      transudative pleural effusions. This finding allows for further exploration
      regarding how underexpression of pigment epithelium-derived factor may relate to
      the pathogenesis of malignant pleural effusions.

PMID- 16899478
TI  - ErbB receptor regulation by dexamethasone in mouse type II epithelial cells.
AB  - Glucocorticoids stimulate foetal surfactant synthesis. Therefore, they are used
      in impending pre-term birth. One mechanism of action on surfactant synthesis is
      through the induction of neuregulin (NRG) secretion by foetal lung fibroblasts.
      The direct effects on signalling pathways, and specifically on erbB receptors in
      foetal type II cell surfactant synthesis, are less well understood. The present
      authors studied the effect of known promoters of foetal surfactant synthesis
      (namely dexamethasone and mature (i.e. NRG-containing) fibroblast-conditioned
      medium (FCM)) on erbB receptor activation, protein content and dimerisation
      patterns in foetal mouse lung type II cells. Dexamethasone inhibited surfactant
      synthesis in immature type II cells at day (d)16 of gestation, while the mature
      FCM had stimulatory effects. Both treatments directly stimulated surfactant
      synthesis in more mature (d17) cells. At this gestational day, dexamethasone had
      only a small effect on phosphorylation, but it stimulated the protein levels of
      all four erbB receptors. Dexamethasone effects were distinct from those of mature
      FCM, which stimulated both protein content and phosphorylation of all erbB
      receptors and of the signalling intermediate phospholipase Cgamma. Dexamethasone
      modulated erbB receptor dimerisation patterns, such that erbB2 became the main
      dimerisation partner for erbB4. In conclusion, dexamethasone signalling involves
      erbB receptors in foetal type II cells, in a manner similar to, but distinct
      from, neuregulin-containing fibroblast-conditioned medium signalling.

PMID- 16899479
TI  - Systemic sensitivity to corticosteroids in smokers with asthma.
AB  - Cigarette smokers with asthma are insensitive to the therapeutic effects of
      corticosteroids. It is not known whether this insensitivity to corticosteroids in
      smokers affects tissue sites beyond the airways. A total of 75 asthmatic subjects
      (39 smokers) and 78 healthy controls (30 smokers) were recruited to an
      observational study. The cutaneous and peripheral blood lymphocyte responses to
      corticosteroids were measured. The cutaneous vasoconstrictor response to topical
      beclometasone was measured by applying different concentrations of beclometasone
      solutions to the skin in a random double-blind manner. The degree of blanching at
      each concentration was graded after 18 h. The sensitivity of peripheral blood
      lymphocytes to corticosteroids was assessed by measuring the suppressive effect
      of dexamethasone on lymphocyte proliferation stimulated by phytohaemagglutinin
      (PHA). Total mean+/-sd cutaneous vasoconstrictor response score to beclometasone
      was reduced in smokers with asthma to 5.39+/-3.58 versus 7.26+/-3.05 in never
      smokers with asthma; and in all smokers to 6.47+/-3.33 versus 7.86+/-2.81 in all
      never-smokers. The sensitivity to corticosteroids of lymphocytes stimulated by
      PHA was similar between groups. In conclusion, smokers with asthma have an
      impaired cutaneous vasoconstrictor response to topical corticosteroids compared
      with never-smokers with asthma. This finding suggests that the insensitivity to
      corticosteroids in smokers with asthma affects tissue sites other than the
      airways.

PMID- 16899480
TI  - Characterisation of dendritic cell subsets in lung cancer micro-environments.
AB  - The aim of the current study was to seek evidence for a correlation between
      mediators present in lung cancer micro-environments and subsets of dendritic
      cells (DCs) infiltrating these tumours. Immunohistochemistry and recently
      available antibodies were used to define the phenotype of DCs present in surgical
      biopsies from 12 patients with lung carcinomas, and the local expression of
      chemokines potentially involved in the recruitment of these cells was evaluated,
      both at mRNA and protein levels. Real-time PCR was used to analyse the expression
      of mRNA coding for cytokines known to influence the maturation of DCs in vitro.
      Different subsets of myeloid DCs were present in lung cancers, but no
      plasmocytoid DCs were identified. Both Langerhans cells and CD1a+/Langerin cells
      were interspersed among tumour cells, in numbers that were correlated to the
      amounts of CC chemokine ligand 20 produced in these tumours. In most specimens,
      DC-specific intercellular adhesion molecule-grabbing nonintegrin-positive DCs
      were also present at the periphery of the tumour beds. No DC-lysosomal associated
      membrane protein-positive DCs were identified and CD83+ DCs were rarely present
      in the tumour stroma. All tumours expressed interleukin (IL)-10, transforming
      growth factor-beta and vascular endothelial growth factor, whereas IL-12 was
      virtually absent. Thus, various types of dendritic cells infiltrate lung
      carcinomas and display an immature phenotype, presumably because of the
      inhibitory cytokine micro-environment.

PMID- 16899481
TI  - Recommended standards for modern tuberculosis laboratory services in Europe.
AB  - The principles underpinning these standards are that any tuberculosis laboratory
      based diagnostic procedure should be performed by appropriately trained staff,
      working to standardised operating procedures in appropriately equipped and safe
      laboratories, against clear national and international proficiency and quality
      standards. Quality should be the pre-eminent criteria, not cost. The standards
      are technologically feasible, but initially may not be within the financial
      capacity of all laboratories. There is a requirement for government and
      international donors to adequately fund an appropriate safe infrastructure to
      enable staff to deliver accurate and timely results at whatever level of activity
      they are performing. There is a need for national reference laboratories to train
      a new cadre of mycobacterial laboratory experts. This will require the funding of
      appropriate individuals at these centres to train and assist in the
      implementation of good laboratory practice and evaluation to build sustainable
      capacity. Further operational research is needed to establish the optimal
      configuration of new technologies to determine isoniazid, rifampicin and second
      line drug susceptibility in mycobacterial cultures and also, increasingly,
      directly on specimens. Improved integration of laboratory medicine as a core part
      of all tuberculosis programmes is needed to achieve and maximise the potential of
      new developments.

PMID- 16899482
TI  - The effect of Pseudomonas aeruginosa on pulmonary function in patients with
      bronchiectasis.
AB  - Bronchiectasis patients are susceptible to infection with Pseudomonas aeruginosa.
      Isolation is associated with increased severity of disease, greater airflow
      obstruction and poorer quality of life. It is not known whether infection by P.
      aeruginosa is a marker of disease severity or contributes to disease progression.
      Consecutive non-cystic fibrosis adult bronchiectasis outpatients (n = 163) with
      multiple sputum cultures and follow-up pulmonary function tests were designated,
      according to isolation of P. aeruginosa, as "never infected" (group 1; n = 67),
      "intermittently isolated" (group 2; n = 82) and "chronically infected" (group 3;
      n = 14). Based upon change in forced expiratory volume in one second (FEV(1)) %
      predicted levels at >or=2 yrs after presentation, longitudinal behaviour was
      characterised as "improvement" (>or=10% rise), "decline" (>or=10% fall) or
      "stability". Baseline pulmonary-function tests and longitudinal behaviour were
      examined in relation to pseudomonas status. There was no difference between the
      groups in age, sex, smoking habit or length of follow-up. Baseline FEV(1) levels
      were highest in group 1 (mean+/-sd: 77.4+/-24.3) and higher in group 2 (67.3+/
      25.7) than in group 3 (55.2+/-18.5). The same significant trends were seen for
      baseline FEV(1)/forced vital capacity ratios and diffusing capacity of the lung
      for carbon monoxide levels. Subsequent longitudinal behaviour was linked to
      baseline FEV(1) levels, which were lowest in patients with improvement and lower
      in association with decline than with stability. However, longitudinal behaviour
      did not differ between groups 1, 2 and 3, either before or after adjustment for
      baseline FEV(1) levels. Infection by Pseudomonas aeruginosa occurs in
      bronchiectasis patients with more severe impairment of pulmonary function but
      does not influence rate of decline in pulmonary function either before or after
      adjustment for baseline disease severity. Thus, Pseudomonas aeruginosa is a
      marker of bronchiectasis severity but is not linked to an accelerated decline in
      pulmonary function.

PMID- 16899483
TI  - Induction of mesenchymal cell phenotypes in lung epithelial cells by adenovirus
      E1A.
AB  - Epithelial-mesenchymal transformation is now recognised as an important feature
      of tissue remodelling. The present report concerns the role of adenovirus
      infection in inducing this transformation in an animal model of chronic
      obstructive pulmonary disease. Guinea pig primary peripheral lung epithelial
      cells (PLECs) transfected with adenovirus E1A (E1A-PLECs) were compared to guinea
      pig normal lung fibroblasts (NLFs) transfected with E1A (E1A-NLFs). These cells
      were characterised by PCR, immunocytochemistry, electron microscopy, and Western
      and Northern blot analyses. Electrophoretic mobility shift assays were performed
      in order to examine nuclear factor (NF)-kappaB and activator protein (AP)-1
      binding activities. E1A-PLECs and E1A-NLFs positive for E1A DNA, mRNA and protein
      expressed cytokeratin and vimentin but not smooth muscle alpha-actin. Both
      exhibited cuboidal morphology and junctional complexes, but did not contain
      lamellar bodies or express surfactant protein A, B or C mRNAs. These two cell
      types differed, however, in their NF-kappaB and AP-1 binding after
      lipopolysaccharide stimulation, possibly due to differences in the expression of
      the subunits that comprise these transcriptional complexes. E1A transfection
      results in the transformation of peripheral lung epithelial cells and normal lung
      fibroblasts to a phenotype intermediate between that of the two primary cells. It
      is postulated that this intermediate phenotype may play a major role in the
      remodelling of the airways in chronic obstructive pulmonary disease associated
      with persistence of adenovirus E1A DNA.

PMID- 16899484
TI  - Humoral immune response against 38-kDa and 16-kDa mycobacterial antigens in
      tuberculosis.
AB  - Several ELISA tests based on mycobacterial antigens have been used for the rapid
      diagnosis of tuberculosis (TB), although demonstration of Mycobacterium
      tuberculosis in a smear or culture is the most reliable method. In the present
      study, the diagnostic value of 16-kDa and 38-kDa mycobacterial antigens was
      investigated in patients who were diagnosed with tuberculosis by clinical and/or
      bacteriological findings in Turkey. The PATHOZYME-TB Complex Plus commercial
      ELISA kit was used for measuring immunoglobulin G against 38-kDa and 16-kDa
      recombinant antigens. Humoral immune response was analysed in a group of 179 TB
      patients (143 smear-positive, 19 smear-negative, eight lymphadenitis and nine
      pleuritis), 15 inactive TB cases and in control groups consisting of 40 healthy
      volunteers and 20 subjects with pulmonary diseases other than TB. The
      sensitivity, specifity, positive predictive value and negative predictive value
      of the test were determined at 52.5%, 93.3%, 95.9% and 39.7%, respectively in TB
      cases. Antibodies were detected at above cut-off level in three (20%) out of 15
      subjects with inactive TB. In conclusion, the ELISA test has a very good
      specifity and an acceptable sensitivity and positive predictive value. It is
      thought that it could be used in combination with other methods to increase
      diagnostic accuracy, especially for culture-negative tuberculosis cases, which
      are difficult to diagnose.

PMID- 16899486
TI  - EU-USA pathology panel for uniform diagnosis in randomised controlled trials for
      HRCT screening in lung cancer.
AB  - Randomised controlled trials for lung cancer screening using high-resolution
      computed tomography are now underway. In order to allow effective future
      comparison of the different trials, as well as strengthening conclusions based
      upon the analysis of larger data sets, uniformity and consistency of pathology
      diagnosis are essential. The aim of the present study was to determine the
      effectiveness of the learning process in this difficult area of diagnostic
      pathology. Eight pathologists received two CD-ROMs, each with digital images of
      30 cases. After diagnosing the first series, selected background reading was
      provided. Kappa (kappa) scores were calculated for each pathologist and category,
      and were compared to the consensus score. The readings of the first series showed
      a moderate agreement kappa score: mean+/-sd for category numbers 8 (all eight
      categories) and 2 were 0.53+/-0.05 and 0.65+/-0.04, respectively. The kappa 2
      score distinguished between categories denoting benign and malignant lesions. The
      second series resulted in a good agreement kappa score: 0.65+/-0.06 for category
      number 8 and 0.81+/-0.02 for category number 2. In conclusion, this study
      demonstrates that screen-detected cases pose particular problems for pathologists
      and that a trained pathology panel serving randomised controlled trials is likely
      to lead to more consistent and accurate tissue diagnosis.

PMID- 16899485
TI  - Long-term outcome in pulmonary arterial hypertension patients treated with
      subcutaneous treprostinil.
AB  - Pulmonary arterial hypertension (PAH) is fatal if untreated. Intravenous
      epoprostenol improves exercise capacity and haemodynamics in PAH, and increases
      survival in idiopathic PAH (IPAH). To evaluate the effects of subcutaneous (SC)
      treprostinil, a longer-acting prostacyclin analogue, followed by the addition of
      other PAH therapies if needed, 860 PAH patients treated with SC treprostinil for
      up to 4 yrs were followed. Survival is reported as Kaplan-Meier estimates. For
      332 IPAH patients with baseline haemodynamics, observed survival is also compared
      with predicted survival using the National Institute of Health formula. Out of
      the 860 patients, 199 (23%) discontinued due to adverse events, 136 (16%) died,
      117 (14%) discontinued due to deterioration, 29 (3%) withdrew consent and 11 (1%)
      underwent transplantation. In total, 97 patients (11%) switched from SC
      treprostinil to an alternative prostacyclin analogue; bosentan was added in 105
      patients (12%) and sildenafil in 25 (3%). In conclusion, survival was 87-68% over
      1-4 yrs for all 860 patients and 88-70% over 1-4 yrs with subcutaneous
      treprostinil monotherapy. For the idiopathic pulmonary arterial hypertension
      subset with baseline haemodynamics (n = 332), survival was 91-72% over 1-4 yrs.
      In contrast, predicted survival was 69-38% over 1-4 yrs. The safety profile for
      long-term subcutaneous treprostinil was consistent with previous short-term
      trials with no unexpected adverse events.

PMID- 16899487
TI  - Reduced bronchial CD4+ T-cell density in smokers with occupational asthma.
AB  - Cigarette smoking may alter bronchial inflammation in asthma. Multicolour
      immunohistofluorescent examination on bronchial cryosections was used to examine
      bronchial inflammatory cell infiltrate in patients with occupational asthma.
      Monoclonal antibodies to CD3, CD4, CD8, T-cell receptor-delta1, CD68 and human
      leukocyte antigen-DR were combined to identify T-cell subsets and macrophages in
      bronchial biopsies from 20 workers with occupational asthma (12 smokers and eight
      nonsmokers), 15 healthy workers (seven smokers and eight nonsmokers) and 10
      nonsmoking, nonexposed controls. The increased subepithelial CD4+ T-cell density
      in nonsmoking asthmatics was not present in smoking asthmatics, who had the
      lowest CD4+ T-cell density of all groups. The decreased subepithelial CD4+ and
      CD8+ T-cell density correlated with a reduction in lung function, as measured by
      percentage predicted forced expiratory volume in one second, in smoking
      asthmatics only. Although smoking asthmatics had a significantly increased number
      of intraepithelial CD8+ T-cells and macrophages compared with nonsmoking
      asthmatics, the proportion of gammadelta-T-cells was significantly decreased in
      both asthmatic groups. Smoking asthmatics had a distinctly different distribution
      of T-cell subsets compared with nonsmoking asthmatics. The accumulation of
      subepithelial CD4+ T-cells, which was observed in nonsmoking asthmatics, appeared
      to be inhibited in smoking asthmatics, suggesting a smoking-induced bronchial
      immune modulation, at least in occupational asthma in the aluminium industry.

PMID- 16899488
TI  - Is bronchoscopic lung biopsy helpful in the management of patients with diffuse
      lung disease?
AB  - Few studies have evaluated how the results of bronchoscopic lung biopsy (BLB)
      affect clinical management. The objective of the present study was to evaluate
      the clinical usefulness of BLB in the overall management of patients with diffuse
      pulmonary diseases. The study was a retrospective analysis of patients who
      underwent fluoroscopy-guided BLB over a 2-yr period. Patients whose biopsy was of
      a lung mass or single dominant lung nodule were excluded. The usefulness of BLB
      was assessed to determine whether the results affected the clinical management of
      these patients. During the study period, 603 patients underwent 651 BLB
      procedures. The results of BLB were clinically helpful in 494 (75.9%) out of 651
      procedures. No diagnostic abnormality was identified in 107 (16.4%) out of the
      651 biopsy procedures. This finding was clinically helpful in 59 (55.1%) out of
      107 procedures, as the results excluded specific processes suspected before BLB.
      In 52 procedures (8% of all BLB), no lung parenchyma was obtained. In conclusion,
      bronchoscopic lung biopsy is a clinically useful test in approximately 75% of
      procedures. In the 25% of bronchoscopic lung biopsies that were clinically
      unhelpful, the reason for failure in approximately one-third of patients was the
      failure of the procedure to obtain an adequate quantity of lung parenchyma for a
      meaningful histological analysis.

PMID- 16899489
TI  - Solvated docking: introducing water into the modelling of biomolecular complexes.
AB  - MOTIVATION: Interfacial water, which plays an important role in mediating
      biomolecular interactions, has been neglected in the modelling of biomolecular
      complexes. METHODS: We present a solvated docking approach that explicitly
      accounts for the presence of water in protein-protein complexes. Our solvated
      docking protocol is based on the concept of the first encounter complex in which
      a water layer is present in-between the molecules. It mimics the pathway from
      this initial complex towards the final assembly in which most waters have been
      expelled from the interface. Docking is performed from solvated biomolecules and
      waters are removed in a biased Monte Carlo procedure based on water-mediated
      contact propensities obtained from an analysis of high-resolution crystal
      structures. RESULTS: We demonstrate the feasibility of this approach for protein
      protein complexes representing both 'wet' and 'dry' interfaces. Solvated docking
      leads to improvements both in quality and scoring. Water molecules are recovered
      that closely match the ones in the crystal structures. AVAILABILTY: Solvated
      docking will be made available in the future release of HADDOCK version 2.0
      (http://www.nmr.chem.uu.nl/haddock).

PMID- 16899490
TI  - MASQOT-GUI: spot quality assessment for the two-channel microarray platform.
AB  - MASQOT-GUI provides an open-source, platform-independent software pipeline for
      two-channel microarray spot quality control. This includes gridding,
      segmentation, quantification, quality assessment and data visualization. It hosts
      a set of independent applications, with interactions between the tools as well as
      import and export support for external software. The implementation of automated
      multivariate quality control assessment, which is a unique feature of MASQOT-GUI,
      is based on the previously documented and evaluated MASQOT methodology. Further
      abilities of the application are outlined and illustrated. AVAILABILITY: MASQOT
      GUI is Java-based and licensed under the GNU LGPL. Source code and installation
      files are available for download at http://masqot-gui.sourceforge.net/

PMID- 16899491
TI  - Identification of regulatory modules by co-clustering latent variable models:
      stem cell differentiation.
AB  - MOTIVATION: An important issue in stem cell biology is to understand how to
      direct differentiation towards a specific cell type. To elucidate the mechanism,
      previous studies have focused on identifying the responsible gene regulators,
      which have, however, failed to provide a systemic view of regulatory modules. To
      obtain a unified description of the regulatory modules, we characterized major
      stem cell species by employing a co-clustering latent variable model (LVM). The
      LVM-based method allowed us to elucidate the cell type-specific transcription
      factors, using genomic sequences as well as expression profiles. RESULTS: We used
      a list of genes enriched in each of 21 stem cell subpopulations, and their
      upstream genomic sequences. The LVM-based study allowed us to uncover the
      regulatory modules for each stem cell cluster, e.g. GABP and E2F for the
      proliferation phase, and Ap2alpha and Ap2gamma for the quiescence phase.
      Furthermore, the identities of the stem cell clusters were well revealed by the
      constituent genes that were directly targeted by the modules. Consequently, our
      analytical framework was demonstrated to be useful through a detailed case study
      of stem cell differentiation and can be applied to problems with similar
      characteristics.

PMID- 16899493
TI  - Statistically designing microarrays and microarray experiments to enhance
      sensitivity and specificity.
AB  - Gene expression signatures from microarray experiments promise to provide
      important prognostic tools for predicting disease outcome or response to
      treatment. A number of microarray studies in various cancers have reported such
      gene signatures. However, the overlap of gene signatures in the same disease has
      been limited so far, and some reported signatures have not been reproduced in
      other populations. Clearly, the methods used for verifying novel gene signatures
      need improvement. In this article, we describe an experiment in which microarrays
      and sample hybridization are designed according to the statistical principles of
      randomization, replication and blocking. Our results show that such designs
      provide unbiased estimation of differential expression levels as well as powerful
      tests for them.

PMID- 16899492
TI  - Molecular cloning and characterization of a novel human beta1,3
      glucosyltransferase, which is localized at the endoplasmic reticulum and
      glucosylates O-linked fucosylglycan on thrombospondin type 1 repeat domain.
AB  - Protein O-linked fucosylation is an unusual glycosylation associated with many
      important biological functions such as Notch signaling. Two fucosylation pathways
      synthesizing O-fucosylglycans have been reported on cystein-knotted proteins,
      that is, on epidermal growth factor-like (EGF-like) domains and on thrombospondin
      Type 1 repeat (TSR) domains. We report here the molecular cloning and
      characterization of a novel beta1,3-glucosyltransferase (beta3Glc-T) that
      synthesizes a Glcbeta1,3Fucalpha- structure on the TSR domain. We found a novel
      glycosyltransferase gene with beta1,3-glycosyltransferase (beta3GT) motifs in
      databases. The recombinant enzyme expressed in human embryonic kidney 293T
      (HEK293T) cells exhibited glucosyltransferase activity toward fucose-alpha-para
      nitrophenyl (Fucalpha-pNp). Thin-layer chromatography (TLC) analysis revealed
      that the product of the recombinant enzyme migrated to the same position as did
      the product of endogenous beta3Glc-T of Chinese hamster ovary (CHO) cells. The
      two products could be digested by beta-glucosidase from almond and by exo-1,3
      beta-glucanase from Trichoderma sp. These results strongly suggested that the
      product has the structure of Glcbeta1-3Fuc. Therefore, we named this novel enzyme
      beta3Glc-T. Immunostaining revealed that FLAG-tagged beta3Glc-T is an enzyme
      residing in the endoplasmic reticulum (ER) via retention signal, "REEL," which is
      a KDEL-like sequence, at the C-terminus. The TSR domain expressed in Escherichia
      coli was first fucosylated by the recombinant protein O-fucosyltransferase 2
      (POFUT2), after which it became an acceptor substrate for the recombinant
      beta3Glc-T, which could apparently transfer Glc to the fucosylated TSR domain.
      Our results suggest that a novel glycosyltransferase, beta3Glc-T, contributes to
      the elongation of O-fucosylglycan and that this occurs specifically on TSR
      domains.

PMID- 16899494
TI  - Open source tools and toolkits for bioinformatics: significance, and where are
      we?
AB  - This review summarizes important work in open-source bioinformatics software that
      has occurred over the past couple of years. The survey is intended to illustrate
      how programs and toolkits whose source code has been developed or released under
      an Open Source license have changed informatics-heavy areas of life science
      research. Rather than creating a comprehensive list of all tools developed over
      the last 2-3 years, we use a few selected projects encompassing toolkit
      libraries, analysis tools, data analysis environments and interoperability
      standards to show how freely available and modifiable open-source software can
      serve as the foundation for building important applications, analysis workflows
      and resources.

PMID- 16899495
TI  - Bio-ontologies: current trends and future directions.
AB  - In recent years, as a knowledge-based discipline, bioinformatics has been made
      more computationally amenable. After its beginnings as a technology advocated by
      computer scientists to overcome problems of heterogeneity, ontology has been
      taken up by biologists themselves as a means to consistently annotate features
      from genotype to phenotype. In medical informatics, artifacts called ontologies
      have been used for a longer period of time to produce controlled lexicons for
      coding schemes. In this article, we review the current position in ontologies and
      how they have become institutionalized within biomedicine. As the field has
      matured, the much older philosophical aspects of ontology have come into play.
      With this and the institutionalization of ontology has come greater formality. We
      review this trend and what benefits it might bring to ontologies and their use
      within biomedicine.

PMID- 16899496
TI  - The Life Sciences Semantic Web is full of creeps!
AB  - The Semantic Web for the Life Sciences (SWLS), when realized, will dramatically
      improve our ability to conduct bioinformatics analyses using the vast and growing
      stores of web-accessible resources. This ability will be achieved through the
      widespread acceptance and application of standards for naming, representing,
      describing and accessing biological information. The W3C-led Semantic Web
      initiative has established most, if not all, of the standards and technologies
      needed to achieve a unified, global SWLS. Unfortunately, the bioinformatics
      community has, thus far, appeared reluctant to fully adopt them. Rather, we are
      seeing what could be described as 'semantic creep'-timid, piecemeal and ad hoc
      adoption of parts of standards by groups that should be stridently taking a
      leadership role for the community. We suggest that, at this point, the primary
      hindrances to the creation of the SWLS may be social rather than technological in
      nature, and that, like the original Web, the establishment of the SWLS will
      depend primarily on the will and participation of its consumers.

PMID- 16899497
TI  - Physiotherapy management of non-specific back and neck pain.

PMID- 16899498
TI  - Very recent onset rheumatoid arthritis: clinical and serological patient
      characteristics associated with radiographic progression over the first years of
      disease.
AB  - OBJECTIVES: Despite early recognition and disease modifying anti-rheumatic drug
      (DMARD) treatment, a sizable proportion of early rheumatoid arthritis (RA)
      patients show radiological progression. This study was performed to determine the
      frequency of erosive arthritis and the pace of radiological progression in an
      inception cohort of patients with very early RA (<or=3 months after onset of
      symptoms). METHODS: In order to determine possible prognostic factors for
      development of erosive disease, we linked the clinical features of these patients
      to radiological progression in a regression model. About 55 patients with RA and
      follow-up of at least 3 yrs were analysed. All had complete series of clinical,
      serological and radiographic assessments. Radiographs were scored according to
      the Larsen method. RESULTS: Erosive disease developed in 63.6% of the patients
      over 3 yrs, with the majority (74.3%) appearing already in the first and 97.2% by
      the end of the second year. Among all variables available, rheumatoid factor (RF)
      and/or anti-cyclic citrullinated peptide (anti-CCP) first presentation were the
      most predictive for both development of erosions and the degree of radiological
      progression. None of the clinical variables at the onset was useful to
      discriminate between erosive and non-erosive patients. In the final regression
      model, however, cumulative clinical activity substantially contributed to
      explaining radiological progression. CONCLUSION: Despite early treatment,
      substantial damage occurred in some patients and was associated with presence of
      strong 'constitutive' predictors such as anti-CCP and RF as well as presence of
      high long-term clinical disease activity as indicated by C-reactive protein
      (CRP), swollen joint counts and the absence of a good clinical response (assessed
      by the failure to achieve lasting low disease activity).

PMID- 16899499
TI  - Individual fracture risk and the cost-effectiveness of bisphosphonates in
      patients using oral glucocorticoids.
AB  - OBJECTIVES: There are few data on the cost-effectiveness of bisphosphonates with
      oral glucocorticoids (GCs). An individual patient-based pharmaco-economic model
      was developed. METHODS: Data were obtained from a cohort of oral GC users aged
      40+ (n = 190 000) in the UK General Practice Research Database. Individualized
      fracture and mortality risks were calculated specific for age, sex, daily and
      cumulative GC dose, indication and other clinical risk factors. UK costs of
      medication and direct costs of fracture were obtained from National Institute for
      Clinical Excellence and used to estimate costs per quality-adjusted life-year
      (QALY) gained and fracture prevented for bisphosphonates in patients treated for
      5 yrs with GCs. RESULTS: With the use of 5 mg GCs daily, the cost per one QALY
      gained with bisphosphonates was 41k UK pounds (95% confidence intervals 22-72k)
      in women aged <60 [men 40k pounds (29-54k)], 17k pounds (13-24k) in women aged 60
      79 [men 43k pounds (31-60k)], 5k pounds(3-6k) in women aged 80+ [men 35k pounds
      (25-46k)]. With 15 mg GC, these figures were 17k pounds (14-21k), 13k pounds (10
      16k) and 15k pounds (9-26k) in women and 22k pounds (17-26k), 34 pounds (23-53k)
      and 33k pounds (27-42k) in men, respectively. When stratifying by overall
      fracture risk and life expectancy at the start of GC therapy, cost per QALY
      increased with decreasing life expectancy. Patients with rheumatoid arthritis had
      comparatively better cost-effectiveness, given higher fracture risk and better
      life expectancy. CONCLUSIONS: The cost-effectiveness of bisphosphonates varied
      substantially. Bisphosphonates can be considered cost-effective in patients with
      higher fracture risks, such as elderly patients (with a life expectancy over 5
      yrs), and younger patients with a fracture history, low body mass index,
      rheumatoid arthritis or using high GC doses.

PMID- 16899500
TI  - A comparison of clinical vs ultrasound determined synovitis in rheumatoid
      arthritis utilizing gray-scale, power Doppler and the intravenous microbubble
      contrast agent 'Sono-Vue'.
AB  - OBJECTIVES: Synovitis in rheumatoid arthritis (RA) is assessed clinically by the
      presence of joint tenderness and swelling. Synovial thickening and increased
      vascularity may also be detected by high-resolution ultrasonography (US) and
      power Doppler (PD). This study investigated the relationship between clinical and
      sonographic features of synovial disease utilizing US, PD and the contrast agent
      Sono-Vue. METHODS: Forty RA patients were recruited. One proximal inter
      phalangeal or metacarpophalangeal joint was selected per patient, as being
      unambiguously either: swollen and tender, just swollen, just tender or neither
      swollen nor tender (Nil). Ten joints were selected per clinical group. On US, the
      mean synovial thickness was measured and synovial hypertrophy and erosions were
      graded subjectively. Synovial vascularity demonstrated by PD was scored
      subjectively pre- and post-contrast. RESULTS: All grades of synovial vascularity
      were found in each clinical group including the Nil group. There were significant
      differences between the four clinical groups for both synovial hypertrophy (P =
      0.024) and PD scores pre- (P = 0.022) and post- (P = 0.039) contrast. Tender-only
      joints showed significantly less vascularity than other groups. Post-contrast,
      the median PD scores increased in all but the Nil group, in some cases from the
      normal to abnormal range. CONCLUSION: Synovitis demonstrated by US and PD is not
      predicted by patterns of disease as described by joint swelling and tenderness
      despite unambiguous selection of joints. Synovial vascularity was the least in
      tender-only joints and was heterogeneous in all other groups, including Nil
      joints. These findings question the reliability of traditional clinical signs in
      RA synovitis assessment.

PMID- 16899502
TI  - Autoantibodies, metalloproteinases and bone markers in rheumatoid arthritis
      patients are unable to predict their responses to infliximab.
AB  - OBJECTIVES: To identify biochemical, immunological and bone markers as predictors
      of rheumatoid arthritis (RA) patients' responses to infliximab. METHODS: A total
      of 76 patients with active RA (American College of Rheumatology criteria),
      refractory to disease-modifying anti-rheumatic drugs, including methotrexate,
      received infliximab (3 mg/kg) infusions at weeks 0, 2, 6, and then every 8 weeks
      in combination with methotrexate or leflunomide. At week 14, infliximab efficacy
      was evaluated using disease activity score (DAS)28. A serum sample, collected
      just before starting infliximab, was tested by ELISA (unless stated otherwise)
      for the following immunological markers: rheumatoid factor by agglutination and
      ELISA (IgA, IgG and IgM isotypes); anti-cyclic citrullinated protein;
      autoantibodies recognizing calpastatin domain I and its 27 C-terminal fragment,
      glucose-6-phosphate isomerase, alpha-enolase; anti-keratin and anti-perinuclear
      factor antibodies (immunofluorescence); biochemical markers: C-reactive protein
      (nephelometry), metalloproteinase-1 and -3, tissue inhibitors of
      metalloproteinases-1 and -2, antioxidants (vitamins A and E; selenium); bone
      resorption markers: pyridinoline, deoxypyridinoline, osteoprotegerin, soluble
      receptor activator of nuclear factor-kappaB ligand, cartilage oligomeric matrix
      protein. Each parameter's predictive value of the response to infliximab was
      analysed using Fisher's exact, Mann-Whitney and chi-square tests. Hierarchical
      clustering was performed with The Institute for Genomic Research (TIGR) multiple
      experiment viewer software. RESULTS: Good, moderate and non-responder rates were
      6.5, 61.8 and 31.5%, respectively. No significant difference was observed between
      responders and non-responders, regardless of the serum parameters considered.
      Analysis of dichotomous or continuous variables failed to identify markers
      predictive of a good or poor response to infliximab. CONCLUSION: The search for
      soluble markers in RA patients' sera likely to predict response to infliximab
      because of their involvement in RA pathogenesis seems disappointing. However,
      because of the limited power to detect smaller differences in biomarkers, the
      present study is a preliminary exploratory analysis.

PMID- 16899503
TI  - 'Quality of pain' in systemic sclerosis.

PMID- 16899504
TI  - Mycophenolate mofetil in diffuse cutaneous systemic sclerosis--a retrospective
      analysis.
AB  - OBJECTIVES: We have assessed indications, duration and tolerability of treatment
      with mycophenolate mofetil (MMF) in patients with diffuse cutaneous systemic
      sclerosis (dcSSc), and compared clinical outcome with a control cohort treated
      with other immunosuppressive drugs. METHODS: The clinical records of 109 patients
      treated with MMF and 63 control subjects receiving other immunosuppressive drugs
      were reviewed. Data covering a 5-yr period from commencement of treatment or
      until last assessment date were collected. RESULTS: MMF and control groups were
      well-matched in terms of basic demographic and clinical parameters. Treatment
      with MMF was very well tolerated. Of all patients, 12% experienced adverse
      reactions with gastrointestinal (GI) tract disturbances and infections being most
      frequent. MMF was discontinued due to disease stabilization in 9%, side effects
      in 8% and no effect on the disease activity in 14% of the patients. There was a
      significantly lower frequency of clinically significant pulmonary fibrosis in the
      MMF-treated cohort (P = 0.037) and significantly better 5-yr survival from
      disease onset and from commencement of treatment (P = 0.027 and P = 0.012,
      respectively). There was no significant difference between the two groups in
      terms of modified Rodnan skin score and forced vital capacity (FVC) change.
      CONCLUSIONS: MMF is very well tolerated and appears to be at least as effective
      as the other current therapies for dcSSc. Our results provide support for further
      evaluation of MMF in a prospective trial.

PMID- 16899505
TI  - Primary care guidelines in rheumatology.

PMID- 16899506
TI  - Top3 processes recombination intermediates and modulates checkpoint activity
      after DNA damage.
AB  - Mutation of TOP3 in Saccharomyces cerevisiae causes poor growth,
      hyperrecombination, and a failure to fully activate DNA damage checkpoints in S
      phase. Here, we report that overexpression of a dominant-negative allele of TOP3,
      TOP3(Y356F), which lacks the catalytic (decatenation) activity of Top3, causes
      impaired S-phase progression and the persistence of abnormal DNA structures (X
      shaped DNA molecules) after exposure to methylmethanesulfonate. The impaired S
      phase progression is due to a persistent checkpoint-mediated cell cycle delay and
      can be overridden by addition of caffeine. Hence, the catalytic activity of Top3
      is not required for DNA damage checkpoint activation, but it is required for
      normal S-phase progression after DNA damage. We also present evidence that the
      checkpoint-mediated cell cycle delay and persistence of X-shaped DNA molecules
      resulting from overexpression of TOP3(Y356F) are downstream of Rad51 function. We
      propose that Top3 functions in S phase to both process homologous recombination
      intermediates and modulate checkpoint activity.

PMID- 16899507
TI  - Characterization of DNA damage in yeast apoptosis induced by hydrogen peroxide,
      acetic acid, and hyperosmotic shock.
AB  - Saccharomyces cerevisiae has been reported to die, under certain conditions, from
      programmed cell death with apoptotic markers. One of the most important markers
      is chromosomal DNA fragmentation as indicated by terminal deoxynucleotidyl
      transferase dUTP nick-end labeling (TUNEL) staining. We found TUNEL staining in
      S. cerevisiae to be a consequence of both single- and double-strand DNA breaks,
      whereas in situ ligation specifically stained double-strand DNA breaks. Cells
      treated with hydrogen peroxide or acetic acid staining positively for TUNEL assay
      stained negatively for in situ ligation, indicating that DNA damage in both cases
      mainly consists of single-strand DNA breaks. Pulsed field gel electrophoresis of
      chromosomal DNA from cells dying from hydrogen peroxide, acetic acid, or
      hyperosmotic shock revealed DNA breakdown into fragments of several hundred
      kilobases, consistent with the higher order chromatin degradation preceding DNA
      laddering in apoptotic mammalian cells. DNA fragmentation was associated with
      death by treatment with 10 mM hydrogen peroxide but not 150 mM and was absent if
      cells were fixed with formaldehyde to eliminate enzyme activity before hydrogen
      peroxide treatment. These observations are consistent with a process that, like
      mammalian apoptosis, is enzyme dependent, degrades chromosomal DNA, and is
      activated only at low intensity of death stimuli.

PMID- 16899509
TI  - Gamma-tubulin is required for proper recruitment and assembly of Kar9-Bim1
      complexes in budding yeast.
AB  - Microtubule plus-end-interacting proteins (+TIPs) promote the dynamic
      interactions between the plus ends (+ends) of astral microtubules and cortical
      actin that are required for preanaphase spindle positioning. Paradoxically, +TIPs
      such as the EB1 orthologue Bim1 and Kar9 also associate with spindle pole bodies
      (SPBs), the centrosome equivalent in budding yeast. Here, we show that deletion
      of four C-terminal residues of the budding yeast gamma-tubulin Tub4 (tub4-delta
      dsyl) perturbs Bim1 and Kar9 localization to SPBs and Kar9-dependent spindle
      positioning. Surprisingly, we find Kar9 localizes to microtubule +ends in tub4
      delta dsyl cells, but these microtubules fail to position the spindle when
      targeted to the bud. Using cofluorescence and coaffinity purification, we show
      Kar9 complexes in tub4-delta dsyl cells contain reduced levels of Bim1. Astral
      microtubule dynamics is suppressed in tub4-delta dsyl cells, but it are restored
      by deletion of Kar9. Moreover, Myo2- and F-actin-dependent dwelling of Kar9 in
      the bud is observed in tub4-delta dsyl cells, suggesting defective Kar9 complexes
      tether microtubule +ends to the cortex. Overproduction of Bim1, but not Kar9,
      restores Kar9-dependent spindle positioning in the tub4-delta dsyl mutant,
      reduces cortical dwelling, and promotes Bim1-Kar9 interactions. We propose that
      SPBs, via the tail of Tub4, promote the assembly of functional +TIP complexes
      before their deployment to microtubule +ends.

PMID- 16899508
TI  - Up-regulation of transient receptor potential canonical 1 (TRPC1) following
      sarco(endo)plasmic reticulum Ca2+ ATPase 2 gene silencing promotes cell survival:
      a potential role for TRPC1 in Darier's disease.
AB  - The mechanism(s) involved in regulation of store operated calcium entry in
      Darier's disease (DD) is not known. We investigated the distribution and function
      of transient receptor potential canonical (TRPC) in epidermal skin cells. DD
      patients demonstrated up-regulation of TRPC1, but not TRPC3, in the squamous
      layers. Ca2+ influx was significantly higher in keratinocytes obtained from DD
      patients and showed enhanced proliferation compared with normal keratinocytes.
      Similar up-regulation of TRPC1 was also detected in epidermal layers of SERCA2+/-
      mice. HaCaT cells expressed TRPC1 in the plasma membrane. Expression of
      sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA)2 small interfering RNA (siRNA)
      in HaCaT cells increased TRPC1 levels and thapsigargin-stimulated Ca2+ influx,
      which was blocked by store-operated calcium entry inhibitors. Thapsigargin
      stimulated intracellular Ca2+ release was decreased in DD cells. DD keratinocytes
      exhibited increased cell survival upon thapsigargin treatment. Alternatively,
      overexpression of TRPC1 or SERCA2-siRNA in HaCaT cells demonstrated resistance to
      thapsigargin-induced apoptosis. These effects were dependent on external Ca2+ and
      activation of nuclear factor-kappaB. Isotretinoin reduced Ca2+ entry in HaCaT
      cells and decreased survival of HaCaT and DD keratinocytes. These findings put
      forward a novel consequence of compromised SERCA2 function in DD wherein up
      regulation of TRPC1 augments cell proliferation and restrict apoptosis. We
      suggest that the anti-apoptotic effect of TRPC1 could potentially contribute to
      abnormal keratosis in DD.

PMID- 16899511
TI  - AgSwe1p regulates mitosis in response to morphogenesis and nutrients in
      multinucleated Ashbya gossypii cells.
AB  - Nuclei in the filamentous, multinucleated fungus Ashbya gossypii divide
      asynchronously. We have investigated what internal and external signals spatially
      direct mitosis within these hyphal cells. Mitoses are most common near cortical
      septin rings found at growing tips and branchpoints. In septin mutants, mitoses
      are no longer concentrated at branchpoints, suggesting that the septin rings
      function to locally promote mitosis near new branches. Similarly, cells lacking
      AgSwe1p kinase (a Wee1 homologue), AgHsl1p (a Nim1-related kinase), and AgMih1p
      phosphatase (the Cdc25 homologue that likely counteracts AgSwe1p activity) also
      have mitoses distributed randomly in the hyphae as opposed to at branchpoints.
      Surprisingly, however, no phosphorylation of the CDK tyrosine 18 residue, the
      conserved substrate of Swe1p kinases, was detected in normally growing cells. In
      contrast, abundant CDK tyrosine phosphorylation was apparent in starving cells,
      resulting in diminished nuclear density. This starvation-induced CDK
      phosphorylation is AgSwe1p dependent, and overexpressed AgSwe1p is sufficient to
      delay nuclei even in rich nutrient conditions. In starving cells lacking septins
      or AgSwe1p negative regulators, the nuclear density is further diminished
      compared with wild type. We have generated a model in which AgSwe1p may regulate
      mitosis in response to cell intrinsic morphogenesis cues and external nutrient
      availability in multinucleated cells.

PMID- 16899510
TI  - Essential role of phosphorylation of MCM2 by Cdc7/Dbf4 in the initiation of DNA
      replication in mammalian cells.
AB  - We report the identification of Cdc7/Dbf4 phosphorylation sites in human MCM2 and
      the determination of the role of Cdc7/Dbf4 phosphorylation of MCM2 in the
      initiation of DNA replication. Using immunoblotting, immunofluorescence, and high
      speed automated cell-imaging analyses with antibodies specific against MCM2 and
      Cdc7/Dbf4 phosphorylated MCM2, we show that the chromatin recruitment and
      phosphorylation of MCM2 are regulated during the cell cycle in HeLa cells.
      Chromatin-bound MCM2 is phosphorylated by Cdc7/Dbf4 during G1/S, which coincides
      with the initiation of DNA replication. Moreover, we show that baculovirus
      expressed purified MCM2-7 complex and its phosphomimetic MCM2E-7 complex display
      higher ATPase activity when compared with the nonphosphorylatable MCM2A-7 complex
      in vitro. Furthermore, suppression of MCM2 expression in HeLa cells by siRNA
      results in the inhibition of DNA replication. The inhibition can be rescued by
      the coexpression of wild type MCM2 or MCM2E but not MCM2A. Taken together, these
      results indicate that Cdc7/Dbf4 phosphorylation of MCM2 is essential for the
      initiation of DNA replication in mammalian cells.

PMID- 16899513
TI  - Developmental origins of hypertension: biology meets statistics.

PMID- 16899512
TI  - WASP-interacting protein is important for actin filament elongation and prompt
      pseudopod formation in response to a dynamic chemoattractant gradient.
AB  - The role of WASP-interacting protein (WIP) in the process of F-actin assembly
      during chemotaxis of Dictyostelium was examined. Mutations of the WH1 domain of
      WASP led to a reduction in binding to WIPa, a newly identified homolog of
      mammalian WIP, a reduction of F-actin polymerization at the leading edge, and a
      reduction in chemotactic efficiency. WIPa localizes to sites of new pseudopod
      protrusion and colocalizes with WASP at the leading edge. WIPa increases F-actin
      elongation in vivo and in vitro in a WASP-dependent manner. WIPa translocates to
      the cortical membrane upon uniform cAMP stimulation in a time course that
      parallels F-actin polymerization. WIPa-overexpressing cells exhibit multiple
      microspike formation and defects in chemotactic efficiency due to frequent
      changes of direction. Reduced expression of WIPa by expressing a hairpin WIPa (hp
      WIPa) construct resulted in more polarized cells that exhibit a delayed response
      to a new chemoattractant source due to delayed extension of pseudopod toward the
      new gradient. These results suggest that WIPa is required for new pseudopod
      protrusion and prompt reorientation of cells toward a new gradient by initiating
      localized bursts of actin polymerization and/or elongation.

PMID- 16899514
TI  - Protecting the microvasculature: a Tie-ght connection to ameliorating chronic
      kidney disease?

PMID- 16899515
TI  - Hemodialysis acutely improves hepatic CYP3A4 metabolic activity.
AB  - The uremic syndrome remains poorly understood despite the widespread availability
      of dialysis for almost four decades. To date, assessment of the biologic activity
      of uremic toxins has focused primarily on in vitro effects, rather than on
      specific biochemical pathways or enzymatic activity in vivo. The activity of
      cytochrome P450 (CYP) 3A4, the most important enzyme in human drug metabolism, is
      decreased in uremia. The purpose of this study was to assess the effect of
      hemodialysis and hence varying concentrations of uremic toxins on CYP3A4 activity
      using the 14C-erythromycin breath test and the traditional phenotypic trait
      measure, 20-min 14CO2 flux. CYP3A4 activity increased by 27% postdialysis (P =
      0.002 compared with predialysis) and was significantly inversely related to
      plasma blood urea nitrogen concentration (rs= -0.50, P = 0.012), but not to
      several middle molecules. This is the first study in humans characterizing uremia
      as a state in which hepatic CYP3A4 activity is acutely improved by hemodialysis.

PMID- 16899516
TI  - Renal bone morphogenetic protein-7 protects against diabetic nephropathy.
AB  - Longstanding diabetes causes renal injury with early dropout of podocytes,
      albuminuria, glomerular and tubulointerstitial fibrosis, and progressive renal
      failure. The renal pathology seems to be driven, in part, by TGF-beta and is
      associated with a loss of renal bone morphogenic protein-7 (BMP-7) expression.
      Here, the hypothesis that maintenance of renal (especially podocyte) BMP-7 by
      transgenic expression reduces diabetic renal injury was tested. Diabetic mice
      that expressed the phosphoenolpyruvate carboxykinase promoter-driven BMP-7
      transgene and nondiabetic, transgenic mice as well as diabetic and nondiabetic
      wild-type controls were studied for up to 1 yr. Transgenic expression of BMP-7 in
      glomerular podocytes and proximal tubules prevents podocyte dropout and
      reductions in nephrin levels in diabetic mice. Maintenance of BMP-7 also reduces
      glomerular fibrosis and interstitial collagen accumulation as well as collagen I
      and fibronectin expression. Diabetic wild-type mice develop progressive
      albuminuria, which is substantially reduced in transgenic mice. These effects of
      the BMP-7 transgene occur without changing renal TGF-beta levels. It is concluded
      that maintenance of renal BMP-7 during the evolution of diabetic nephropathy
      reduces diabetic renal injury, especially podocyte dropout. The findings also
      establish a role for endogenous glomerular BMP-7 as an autocrine regulator of
      podocyte integrity in vivo.

PMID- 16899517
TI  - Untreated rejection in 6-month protocol biopsies is not associated with fibrosis
      in serial biopsies or with loss of graft function.
AB  - Donor age, calcineurin inhibitor nephrotoxicity, and acute rejection are the most
      significant predictors of chronic allograft nephropathy. Protocol biopsies, both
      in deceased- and living-donor renal grafts, have shown that cortical
      tubulointerstitial fibrosis correlates with graft survival and function. The
      impact of not treating subclinical acute rejection (SAR) is less clear. In this
      study, 126 de novo renal transplant recipients were randomly assigned to receive
      area-under-the-curve-controlled exposure of either a cyclosporine or a tacrolimus
      based immunosuppressive regimen that included steroids, mycophenolate mofetil,
      and basiliximab induction. Protocol biopsies were taken before and 6 and 12 mo
      after transplantation. The prevalence of SAR was determined retrospectively.
      Fibrosis was evaluated by quantitative digital analysis of Sirius red staining in
      serial biopsies. Donor age correlated significantly with tubulointerstitial
      fibrosis in pretransplantation biopsies and inferior graft function at month 6
      (rtau = -0.26; P = 0.033). Acute rejection incidence was 11.5%, and no clinical
      late rejection occurred. The prevalence of SAR at 6 mo was 30.8% but was not
      associated with differences in serial quantitative Sirius red staining at 6 or 12
      mo, proteinuria, or progressive loss of GFR up to 2 yr. No differences were found
      in donor variables, histocompatibility, rejection history, or exposure of
      immunosuppressants. Controlled individualized calcineurin inhibitor exposure and
      subsequent tapering resulted in a low early acute rejection rate and prevented
      late acute rejection. Because, by design, we did not treat SAR, these results
      provide evidence that asymptomatic infiltrates in 6-mo surveillance biopsies may
      not be deleterious in the intermediate term. There is need for reliable
      biomarkers to prove that not all cell infiltrates are equivalent or that
      infiltrates may change with time.

PMID- 16899518
TI  - Induction of glomerular heparanase expression in rats with adriamycin nephropathy
      is regulated by reactive oxygen species and the renin-angiotensin system.
AB  - Heparan sulfate (HS) in the glomerular basement membrane (GBM) is important for
      regulation of the charge-dependent permeability. Heparanase has been implicated
      in HS degradation in several proteinuric diseases. This study analyzed the role
      of heparanase in HS degradation in Adriamycin nephropathy (AN), a model of
      chronic proteinuria-induced renal damage. Expression of heparanase, HS, and the
      core protein of agrin (to which HS is attached) was determined on kidney sections
      from rats with AN in different experiments. First, expression was examined in a
      model of unilateral AN in a time-course study at 6-wk intervals until week 30.
      Second, rats were treated with the hydroxyl radical scavenger dimethylthiourea
      (DMTU) during bilateral AN induction. Finally, 6 wk after AN induction, rats were
      treated with angiotensin II receptor type 1 antagonist (AT1A) or vehicle for 2
      wk. Heparanase expression was increased in glomeruli of rats with AN, which
      correlated with HS reduction at all time points and in all experiments. Treatment
      with DMTU prevented the increased heparanase expression, the loss of GBM HS, and
      reduced albuminuria. Finally, treatment of established proteinuria with AT1A
      significantly reduced heparanase expression and restored glomerular HS. In
      conclusion, an association between heparanase expression and reduction of
      glomerular HS in AN was observed. The effects of DMTU suggest a role for reactive
      oxygen species in upregulation of heparanase. Antiproteinuric treatment by AT1A
      decreased heparanase expression and restored HS expression. These results suggest
      involvement of radicals and angiotensin II in the modulation of GBM permeability
      through HS and heparanase expression.

PMID- 16899519
TI  - Macroalbuminuria is a better risk marker than low estimated GFR to identify
      individuals at risk for accelerated GFR loss in population screening.
AB  - Macroalbuminuria, erythrocyturia, and impaired renal function are strong
      predictors of poor renal outcome in patients with known renal disease. However,
      the yield of mass screening for these variables to identify individuals who are
      at risk for GFR loss is yet unknown in a Western population. With the use of data
      from the Prevention of Renal and Vascular End-Stage Disease (PREVEND) study, a
      prospective, population-based cohort study, the cardiovascular and renal
      prognosis was investigated in patients with classical renal risk markers:
      Macroalbuminuria (> or =300 mg albumin/24 h urine), erythrocyturia (> or =250
      erythrocytes/L, without leukocyturia), and impaired renal function (both 24-h
      creatinine clearance and Modification of Diet in Renal Disease clearance below
      the fifth percentile of age- and gender-matched control subjects). The 8592
      patients who were included in this study were followed for a 4-yr period. We
      identified 134 patients with macroalbuminuria, 128 with erythrocyturia, and 103
      with impaired renal function. There was only a little overlap among the three
      groups. The prevalence of macroalbuminuria, erythrocyturia, and impaired renal
      function was calculated to be in the general population 0.6, 1.3, and 0.9%,
      respectively. In all three groups, fewer than 30% of patients were known to have
      this laboratory abnormality before screening. The incidence of cardiovascular
      disease was high in the macroalbuminuria group (e.g., the age- and gender
      adjusted hazard ratio for mortality as a result of cardiovascular disease is 2.6
      [1.1 to 6.0]) and for the impaired renal function group (3.4 [1.5 to 8.0]). After
      a mean follow-up of 4.2 yr, the macroalbuminuria group showed a -7.2 ml/min per
      1.73 m2 estimated GFR (eGFR) loss, compared with -2.3 ml/min per 1.73 m2 in the
      control group (difference P < 0.001), whereas the rate of eGFR loss in the
      impaired renal function group (-0.2 ml/min per 1.73 m2; P = 0.18) and the
      erythrocyturia group (-2.6 ml/min per 1.73 m2) was not different from the control
      group. Macroalbuminuria and impaired renal function both predict a worse
      prognosis with respect to cardiovascular morbidity and mortality. However,
      macroalbuminuria is a better risk marker than low eGFR or erythrocyturia to
      identify in population screening of individuals who are at risk for accelerated
      GFR loss.

PMID- 16899520
TI  - Dietary electrolyte-driven responses in the renal WNK kinase pathway in vivo.
AB  - WNK1 and WNK4 are unusual serine/threonine kinases with atypical positioning of
      the catalytic active-site lysine (WNK: With-No-K[lysine]). Mutations in these WNK
      kinase genes can cause familial hyperkalemic hypertension (FHHt), an autosomal
      dominant, hypertensive, hyperkalemic disorder, implicating this novel WNK pathway
      in normal regulation of BP and electrolyte balance. Full-length (WNK1-L) and
      short (WNK1-S) kinase-deficient WNK1 isoforms previously have been identified.
      Importantly, WNK1-S is overwhelmingly predominant in kidney. Recent Xenopus
      oocyte studies implicate WNK4 in inhibition of both thiazide-sensitive co
      transporter-mediated Na+ reabsorption and K+ secretion via renal outer medullary
      K+ channel and now suggest that WNK4 is inhibited by WNK1-L, itself inhibited by
      WNK1-S. This study examined WNK pathway gene expression in mouse kidney and its
      regulation in vivo. Expression of WNK1-S and WNK4 is strongest in distal tubule,
      dropping sharply in collecting duct and with WNK4 also expressed in thick
      ascending limb and the macula densa. These nephron segments that express WNK1-S
      and WNK4 mRNA have major influence on long-term NaCl reabsorption, BP, K+, and
      acid-base balance, processes that all are disrupted in FHHt. In vivo, this novel
      WNK pathway responds with significant upregulation of WNK1-S and WNK4 with high
      K+ intake and reduction in WNK1-S on chronic lowering of K+ or Na+ intake. A two
      compartment distal nephron model explains these in vivo findings and the
      pathophysiology of FHHt well, with WNK and classic aldosterone pathways
      responding to drivers from K+ balance, extracellular volume, and aldosterone and
      cross-talk through distal Na+ delivery regulating electrolyte balance and BP.

PMID- 16899521
TI  - CCL19-IgG prevents allograft rejection by impairment of immune cell trafficking.
AB  - An adaptive immune response is initiated in the T cell area of secondary lymphoid
      organs, where antigen-presenting dendritic cells may induce proliferation and
      differentiation in co-localized T cells after T cell receptor engagement. The
      chemokines CCL19 and CCL21 and their receptor CCR7 are essential in establishing
      dendritic cell and T cell recruitment and co-localization within this unique
      microenvironment. It is shown that systemic application of a fusion protein that
      consists of CCL19 fused to the Fc part of human IgG1 induces effects similar to
      the phenotype of CCR7-/- animals, like disturbed accumulation of T cells and
      dendritic cells in secondary lymphoid organs. CCL19-IgG further inhibited their
      co-localization, which resulted in a marked inhibition of antigen-specific T cell
      proliferation. The immunosuppressive potency of CCL19-IgG was tested in vivo
      using murine models for TH1-mediated immune responses (delayed-type
      hypersensitivity) and for transplantation of different solid organs. In
      allogeneic kidney transplantation as well as heterotopic allogeneic heart
      transplantation in different strain combinations, allograft rejection was reduced
      and organ survival was significantly prolonged by treatment with CCL19-IgG
      compared with controls. This shows that in contrast to only limited prolongation
      of graft survival in CCR7 knockout models, the therapeutic application of a CCR7
      ligand in a wild-type environment provides a benefit in terms of
      immunosuppression.

PMID- 16899522
TI  - Transcriptional profiling of sunflower plants growing under low temperatures
      reveals an extensive down-regulation of gene expression associated with chilling
      sensitivity.
AB  - Being able to sow early to maximize the growing season and to escape drought
      stress has increased the importance of low-temperature tolerance in sunflower.
      Yet knowledge about the molecular basis of sunflower response to low temperature
      is still lacking. To address this issue, nylon microarrays containing >8000
      putative unigenes were developed and used. Early- and late-flowering genotypes
      were sown at 15 degrees C and grown until the two-leaf stage when they were
      subjected to 7 degrees C until the four-leaf stage. The transcriptional profiles
      of low temperature-grown plants (15 degrees C and 7 degrees C) were compared with
      those grown under standard conditions (25 degrees C). Two-step ANOVA
      normalization and analysis models were used to identify the differentially
      expressed genes. A total of 108 cDNA clones having a P-value <10(-3) were found
      to be differentially expressed between the low temperature-grown plants (15
      degrees C and 7 degrees C) and their corresponding two-leaf- and four-leaf-stage
      controls across the two genotypes. About 90% of these genes were down-regulated.
      This includes genes potentially involved in the metabolism of carbohydrate and
      energy, protein synthesis, signal transduction, and transport function. Comparing
      gene expression profiles at 15 degrees C and 7 degrees C revealed that only four
      genes can be considered as differentially expressed, in both genotypes,
      suggesting that similar genetic programmes underlie the response of sunflower
      plants to these temperature regimes. The analysis also revealed that early- and
      late-flowering genotypes respond similarly to low-temperature tolerance as
      justified by the low number of genes showing a significant genotype x treatment
      interaction effect. It seems likely that the down-regulation and/or non-induction
      of genes having a critical role in low-temperature tolerance may be responsible
      for the sensitivity of sunflower plants to low-temperature tolerance. The results
      reported provide an initial characterization of the transcriptome activity of
      sunflower, as a chilling-sensitive plant under suboptimal temperatures, and could
      be of importance to reveal the potential differences between chilling-sensitive
      and chilling-tolerant species.

PMID- 16899523
TI  - Characterization of alanine aminotransferase (AlaAT) multigene family and hypoxic
      response in young seedlings of the model legume Medicago truncatula.
AB  - Four alanine aminotransferases (AlaATs) are expressed in Medicago truncatula. In
      adult plants, two genes encoding mitochondrial isoforms m-AlaAT and alanine
      glyoxylate aminotransferase (AGT), catalysing, respectively, reversible reactions
      of alanine/oxoglutarate<==>glutamate/pyruvate and
      alanine/glyoxylate<==>glycine/pyruvate, were expressed in roots, stems, and
      leaves. A gene encoding a cytosolic (c-AlaAT) isoform, catalysing the same
      reaction as m-AlaAT, was expressed specifically in leaves, while a gene encoding
      an isoform involved in branched chain amino acid metabolism was expressed in
      stems and roots. In young seedlings, only m-AlaAT and AGT were expressed in
      embryo axes. In hypoxic embryo axes, the amounts of transcript and putative
      protein of m-AlaAT (EC 2.6.1.2) increased while those of AGT (EC 2.6.1.44)
      decreased and in vivo enzyme activities changed as revealed by [(15)N]alanine and
      [(15)N]glutamate labelling. Under hypoxia, m-AlaAT catalysed only alanine
      synthesis while glutamate synthesis using alanine as amino donor was inhibited.
      As a result, alanine accumulated as the major amino acid in hypoxic seedlings
      instead of asparagine, in agreement with the involvement of the fermentative
      AlaAT pathway in hypoxia tolerance. Regulation of m-AlaAT at both the
      transcriptional and post-translational levels allowed for an increase in gene
      expression and orientation of the activity of the product of its transcription
      towards alanine synthesis under hypoxia. Labelling experiments showed that
      glycine synthesis occurred at the expense of either alanine or glutamate as amino
      donor, indicating that a glutamate-glyoxylate aminotransferase was operating
      together with AGT in Medicago truncatula seedlings. Both enzymes seemed to be
      inhibited by hypoxia, resulting in a very low amount of glycine in hypoxic
      seedlings.

PMID- 16899524
TI  - HLA-B27-associated acute anterior uveitis in the University Referral Centre in
      North Thailand: clinical presentation and visual prognosis.
AB  - BACKGROUND: Acute anterior uveitis (AAU) is the most frequent type of uveitis
      encountered in the west. Although human leucocyte antigen (HLA)-B27-associated
      ankylosing spondylitis was reported in South East Asia, it is not known whether
      HLA-B27-associated ocular disease is prevalent in Thailand. METHODS: A
      prospective study of 100 unrelated blood donors and 121 consecutive patients with
      AAU was carried out. All people underwent HLA-B27 typing and full ocular
      examination. Radiological examination of the sacroiliac joints was conducted in
      patients with low back pain or arthralgias. RESULTS: The prevalence of HLA-B27
      was 10% among the blood donors in contrast with 44% in the AAU group (p<0.001).
      The clinical characteristics of HLA-B27-associated AAU were similar to those
      published throughout the world (unilaterality in 74%, hypopyon in 31%, recurrent
      AAU in 64%). However, the increased intraocular pressure (IOP) was more common in
      the HLA-B-27-negative group (p = 0.03) than in their HLA-B27-positive
      counterparts. At least 15% of the HLA B27-positive group had radiological signs
      of ankylosing spondylitis. CONCLUSION: The prevalence of HLA-B27 in the
      population without uveitis in Thailand is about 10% and clinical characteristics
      of HLA-B27-positive AAU are similar to those reported in the west. In contrast
      with earlier reports, HLA-B27-negative AAU in Thailand was associated with
      increased IOP and should be further studied.

PMID- 16899525
TI  - Prevalence and risk factors for trachoma and ocular Chlamydia trachomatis
      infection in Niger.
AB  - AIMS: To determine the association of personal and household risk factors for
      trachoma and ocular Chlamydia trachomatis infection in Niger. METHODS: 12
      villages were randomly selected. A census of all households was carried out, and
      651 children aged 1-5 years were randomly selected and examined. Household and
      personal characteristics were determined, trachoma was clinically assessed and a
      swab for ocular C trachomatis infection was taken. RESULTS: The prevalence of
      trachoma was 43% (95% confidence interval (CI) 39% to 47%) and of infection was
      21% (95% CI 18% to 24%). Children aged 3-5 years had a stronger association of
      clinical signs with infection, compared with those aged 1-2 years. Those with
      unclean faces were three times more likely to have clinical trachoma or ocular C
      trachomatis infection, compared with those with clean faces (OR 3.1 (95% CI 1.6
      to 6.2) and 3.0 (95% CI 1.4 to 6.3), respectively). 75% of compounds were within
      30 min of a water source. Flies on the face were a risk factor for trachoma but
      not for C trachomatis infection. CONCLUSIONS: The different association of
      clinical signs with infection in younger versus older children may be an age
      dependent difference in the duration of clinical disease. In Niger, unclean faces
      are a major risk factor for trachoma. The ready availability of water for washing
      suggests that further research on the effect of a strong health education
      campaign promoting clean children is warranted in this area.

PMID- 16899527
TI  - Consent for corneal donation: the effect of age of the deceased, registered
      intent and which family member is asked about donation.
AB  - AIM: To determine whether consent to corneal donation is related to which next of
      kin is asked to consent, the age of the potential donor and the indication about
      donation made by the deceased on their driving licence. METHOD: The Lions New
      South Wales Eye Bank (Sydney, New South Wales, Australia) provides the corneal
      transplantation service for Australia's most populous state. Over the 18-month
      period from 1 July 2004 to 31 December 2005 for all requests for donation,
      records were kept of which next of kin was asked for consent, the age of the
      deceased and the indication about donation by the deceased on their driving
      licence. RESULTS: Over the 18-month study period, 841 people were approached
      about corneal donation. 63.2% of those people approached gave their consent to
      donation. Increasing age of the deceased was significantly positively associated
      with consent to donation (p = 0.006). Multivariable univariate analysis adjusting
      for age of deceased showed that relative type was strongly associated with
      consent (p<0.001), with mothers and fathers more likely to donate than siblings,
      and siblings more likely to donate than children and spouses. An indication of
      willingness to donate on a driving licence was strongly associated with consent
      (p<0.001). CONCLUSIONS: Higher consent rates from older donors have implications
      for policies to maximise corneal procurement. The decision to donate on behalf of
      a deceased family member is complex and influenced by social context. Research
      should investigate individualised strategies to be used when seeking consent from
      particular categories of next of kin.

PMID- 16899526
TI  - Structural and functional assessment of the macular region in patients with
      glaucoma.
AB  - PURPOSE: To investigate the correlation of a structural measure of the macular
      area (optical coherence tomography (OCT)) with two functional measures (10-2
      Humphrey visual field (HVF) and multifocal visual evoked potential (mfVEP)) of
      macular function. METHODS: 55 eyes with open-angle glaucoma were enrolled. The 10
      2 HVF was defined as abnormal if clusters of > or =3 points with p<5%, one of
      which had p<1%, were present. The mfVEP was abnormal if probability plots had >
      or =2 adjacent points with p<1%, or > or =3 adjacent points with p<5% and at
      least one of these points with p<1%. Two criteria were used for the macular OCT:
      (I) > or =2 sectors with p<5% or 1 sector with p<1% and (II) 1 sector with p<5%.
      RESULTS: 54 of the 55 eyes showed an abnormal 10-2 HVF and 50 had central mfVEP
      defects. The two OCT criteria resulted in sensitivities of 85% and 91%. When both
      functional tests showed a defect (in 49 eyes), the OCT was abnormal in 45. For
      the OCT the outer and inner inferior regions were the most likely to be abnormal,
      and both functional techniques were most abnormal in the superior hemifield.
      CONCLUSIONS: Good agreement exists between macular thickness and functional
      defects in patients with glaucoma. Study of the macular region may provide a
      quantitative measure for disease staging and monitoring.

PMID- 16899528
TI  - Selective laser trabeculoplasty versus argon laser trabeculoplasty: results from
      a 1-year randomised clinical trial.
AB  - AIMS: To compare selective laser trabeculoplasty (SLT) and argon laser
      trabeculoplasty (ALT), in terms of intraocular pressure (IOP) lowering, in
      patients with open-angle glaucoma. METHODS: 176 eyes of 152 patients were
      enrolled in this study, 89 in the SLT and 87 in the ALT groups. Patients were
      randomised to receive either SLT or ALT treatment to 180 degrees of the
      trabecular meshwork. Patients were followed up to 12 months after treatment. The
      main outcome measured was IOP lowering at 12 months after treatment, compared
      between the SLT and ALT groups. RESULTS: No significant difference (p = 0.846)
      was found in mean decrease in IOP between the SLT (5.86 mm Hg) and ALT (6.04 mm
      Hg) groups at 1 year or at any other time points, nor were there any significant
      differences in the rate of early or late complications between the two groups.
      CONCLUSIONS: SLT is equivalent to ALT in terms of IOP lowering at 1 year, and is
      a safe and effective procedure for patients with open-angle glaucoma.

PMID- 16899529
TI  - Effects of topical anaesthetics and fluorescein on the real-time PCR used for the
      diagnosis of Herpesviruses and Acanthamoeba keratitis.
AB  - BACKGROUND: The early microbiological diagnosis of corneal infections may prevent
      the condition from worsening. AIM: To study the potential interferences of
      oxybuprocain and fluorescein solutions used by ophthalmologists on the
      performances of the real-time polymerase chain reaction (PCR) carried out as
      routine test for diagnosis of keratitis. METHODS: Quantified suspensions of
      Herpes simplex virus (HSV1), Varicella zoster virus (VZV), Cytomegalovirus (CMV)
      and Acanthamoeba with and without oxybuprocain or fluorescein added before DNA
      extraction were tested by real-time PCR. RESULTS: The capacities of the real-time
      PCR to detect HSV, VZV, CMV and Acanthamoeba were reduced by oxybuprocain and
      fluorescein. Both products diluted to 1/16 reduced the PCR detection capacities
      for more than 2 logs (DNA copies/sample). CONCLUSIONS: The simultaneous
      introduction of fluorescein or topical anaesthetics into the tubes containing the
      specimens to be tested by PCR may lead to false negative results. Because corneal
      specimens for microbiological diagnosis of keratitis are obtained after topical
      administration of anaesthetics and corneal staining with fluorescein,
      ophthalmologists should be aware to rinse the eye surface intensively with
      appropriate eye solutions to minimise the risks of misdiagnosis.

PMID- 16899530
TI  - Intraoperative complications of cataract surgery in the very old.
AB  - AIM: To identify whether the risk of an intraoperative complication of
      phakoemulsification cataract surgery increases with age. METHODS: 1441
      consecutive patients undergoing phakoemulsification cataract surgery were
      assessed preoperatively, and data on the occurrence of intraoperative
      complications were collected prospectively. Data were entered into a computerised
      database, and logistic regression was used to examine evidence of an association
      between age and the risk of an intraoperative complication. In addition, the
      rates of intraoperative complications were compared between patients > or =88
      years and those <88 years, and between patients > or =96 years and those <96
      years. RESULTS: No significant association was found between age and the risk of
      an intraoperative complication. The authors found little evidence that patients >
      or =88 years were at a greater risk of an intraoperative complication than those
      <88 years, or that those > or =96 years are at increased risk; however, numbers
      were small. CONCLUSIONS: These results suggest that age alone is not a major risk
      factor for any intraoperative complications occurring during phakoemulsification
      cataract surgery. This has implications not just for tailoring the risk of
      complications occurring to individual patients but also for meaningful
      comparisons between national complication rates and those of individual surgeons,
      and better selection of cases suitable for instruction.

PMID- 16899531
TI  - Detection by broad-range real-time PCR assay of Chlamydia species infecting human
      and animals.
AB  - BACKGROUND: Tests available for molecular diagnosis of chlamydial infections
      detect Chlamydiatrachomatis, but do not find other Chlamydia species associated
      with genital, ophthalmic, cardiovascular, respiratory or neurological diseases.
      The routine detection of all Chlamydia species would improve the prognosis of
      infected people and guide therapeutic choices. AIM: To design and validate a
      sensitive, specific, reproducible, inexpensive and easy-to-perform assay to
      quantify most Chlamydia species. METHODS: Primers and probe were selected using
      the gene coding for the 16S rRNA. The detection limits were assessed for
      suspensions of Chlamydia trachomatis, Chlamydia psittaci and Chlamydia
      pneumoniae. The performance of this test was compared with that of two commercial
      kits (Amplicor-Roche and Artus) on 100 samples obtained from children with
      trachoma. RESULTS: The detection capacities for Chlamydia trachomatis of the
      broad-range real-time polymerase chain reaction (PCR) were similar or slightly
      better than those obtained with commercial kits (0.2 copies of DNA/microl). Only
      the broad-range PCR identified specimens containing Chlamydia psittaci and
      Chlamydia pneumoniae. The commercial kits and the broad-range assay detected
      Chlamydia species in 5% and in 11%, respectively, of samples from children with
      trachoma. CONCLUSIONS: This new real-time PCR offers a sensitive, reproducible
      assay that produces results in <3 h. With panels of quantified Chlamydia species,
      this real-time PCR can be run with all real-time PCR equipment. Larger trials are
      needed to confirm the utility of this test in diagnosis and for therapeutic
      follow-up.

PMID- 16899532
TI  - Toxoplasmic retinochoroiditis presenting in childhood: clinical findings in a UK
      survey.
AB  - AIM: To compare the clinical findings in children with symptomatic toxoplasmic
      ocular lesions attributable to infection acquired before or after birth. METHODS:
      Cases were prospectively ascertained for 24 months through national surveillance
      units and reference laboratories in the British Isles. Age and presenting
      symptoms, site of lesion and visual impairment in children who were classified as
      acquiring infection either before or after birth on the basis of clinical and
      serological findings were compared. RESULTS: 31 children had toxoplasmic
      retinochoroiditis, 15 had congenital infection and all but three of these
      presented before the age of 4 years. The remaining 16 children acquired
      toxoplasmosis postnatally, and 14 of 16 presented after the age of 10 years. A
      further four children had retinochoroiditis due to other causes. The presence of
      bilateral, multiple or posterior pole lesions did not distinguish between the two
      groups, but most children (16/19; 84%) presenting with acute ocular symptoms had
      postnatally acquired infection. Unilateral visual impairment (Snellen < or =6/18)
      was equally prevalent in the two groups (4/9 before birth v 7/16 after birth;
      p>0.5). Only two children had bilateral visual impairment, both of whom had
      congenital infection. No child was blind. CONCLUSIONS: About 50% of children with
      ocular lesions due to toxoplasmosis had postnatal infection. Retinochoroidal
      lesions due to infection before and after birth were indistinguishable. The
      prognosis for bilateral visual function was good, regardless of when infection
      was acquired.

PMID- 16899535
TI  - Editorial: the significance of psychotherapy in the age of neuroscience.

PMID- 16899534
TI  - The Illness Management and Recovery program: rationale, development, and
      preliminary findings.
AB  - The Illness Management and Recovery (IMR) program was developed based on a
      comprehensive review of research on teaching illness self-management strategies
      to clients with schizophrenia and other severe mental illnesses and "packaged" in
      a resource kit to facilitate dissemination. Despite growing dissemination of this
      program, it has not yet been empirically validated. This article describes the
      development and theoretical underpinnings of the IMR program and presents pilot
      data from the United States and Australia (N = 24, 88% schizophrenia or
      schizoaffective) on the effects of individual-based and group-based treatment
      over the 9-month program and over a 3-month follow-up. High satisfaction was
      reported by participants. Strong improvements over treatment and at follow-up
      were found in clients' self-reported effectiveness in coping with symptoms and
      clinicians' reports of global functioning and moderate improvements in knowledge
      about mental illness, distress related to symptoms, hope, and goal orientation.
      These findings support the feasibility and promise of the IMR program and point
      to the need for controlled research to rigorously evaluate its effects.

PMID- 16899536
TI  - CDC-42 and RHO-1 coordinate acto-myosin contractility and PAR protein
      localization during polarity establishment in C. elegans embryos.
AB  - In C. elegans one-cell embryos, polarity is conventionally defined along the
      anteroposterior axis by the segregation of partitioning-defective (PAR) proteins
      into anterior (PAR-3, PAR-6) and posterior (PAR-1, PAR-2) cortical domains. The
      establishment of PAR asymmetry is coupled with acto-myosin cytoskeleton
      rearrangements. The small GTPases RHO-1 and CDC-42 are key players in
      cytoskeletal remodeling and cell polarity in a number of different systems. We
      investigated the roles of these two GTPases and the RhoGEF ECT-2 in polarity
      establishment in C. elegans embryos. We show that CDC-42 is required to remove
      PAR-2 from the cortex at the end of meiosis and to localize PAR-6 to the cortex.
      By contrast, RHO-1 activity is required to facilitate the segregation of CDC-42
      and PAR-6 to the anterior. Loss of RHO-1 activity causes defects in the early
      organization of the myosin cytoskeleton but does not inhibit segregation of
      myosin to the anterior. We therefore propose that RHO-1 couples the polarization
      of the acto-myosin cytoskeleton with the proper segregation of CDC-42, which, in
      turn, localizes PAR-6 to the anterior cortex.

PMID- 16899537
TI  - Transcriptional control of midbrain dopaminergic neuron development.
AB  - Although loss of midbrain dopaminergic neurons is associated with one of the most
      common human neurological disorders, Parkinson's disease, little is known about
      the specification of this neuronal subtype. Hence, the recent identification of
      major transcriptional determinants regulating the development of these neurons
      has brought much excitement and encouragement to this field. These new findings
      will help to elucidate the genetic program that promotes the generation of
      midbrain dopaminergic neurons. Importantly, these discoveries will also
      significantly advance efforts to differentiate stem cells into midbrain
      dopaminergic neurons that can be used for therapeutic use in treating Parkinson's
      disease.

PMID- 16899538
TI  - Transmembrane domain VII of the human apical sodium-dependent bile acid
      transporter ASBT (SLC10A2) lines the substrate translocation pathway.
AB  - Recent evidence implicating transmembrane (TM) segment 7 of the apical sodium
      dependent bile acid transporter (ASBT) in substrate interaction warranted
      examination of its aqueous accessibility. Therefore, cysteine substitution of 22
      consecutive amino acids was performed against a methanethiosulfonate (MTS)
      resistant background (C270A). Activity and susceptibility to polar MTS
      derivatives [(2-aminoethyl)-methanethiosulfonate (MTSEA), [2
      (trimethylammonium)ethyl]methanethiosulfonate (MTSET), and methanethiosulfonate
      ethylsulfonate (MTSES)] of mutants were evaluated in COS-1 cells. Thr289, Tyr293,
      Gln297, Ala301, Phe307, and Tyr308 represented loss-of-function mutants;
      furthermore, the measurable residual activities for T289C, Y293C, and A301C
      (<or=20% control) proved insensitive to MTS treatment. MTSES and MTSET inhibition
      was confined to residues lining the extracellular half of TM7; amino acids
      situated deeper within the membrane were unaffected. In contrast, the entire
      length of TM7 was susceptible to the relatively smaller MTSEA; moreover, MTSEA
      sensitivity was significantly amended by coapplication with substrates. This
      selective pattern of modification suggests that the highly conserved lower half
      of TM7 lies within a water-filled cavity easily accessible from the extracellular
      milieu, whereas residues approaching the cytosolic/membrane interface reside in
      pores for which accessibility is modulated by molecular volume. Functionally
      inactive and MTS-inaccessible residues (T289C, Y293C, Q297C, and A301C) within
      TM7 may play a structural role critical to transporter function; conversely, MTS
      sensitive residues are spatially distinct and may demarcate a face of the TM
      involved in substrate translocation. In addition, computational analysis of
      solvent-accessible domains identified five key solvent pockets that predominantly
      line the hydrophilic face of TM7. Combined, our data suggest that TM7 plays a
      dominant role in the hASBT translocation process.

PMID- 16899539
TI  - Identification and characterization of new protein chemoattractants in the frog
      skin secretome.
AB  - The vomeronasal organ is a chemosensory organ present in most vertebrates and
      involved in chemical communication. In the last decade, the deciphering of the
      signal transduction process of this organ has progressed. However, less is known
      about the vomeronasal organ ligands and their structure-function relationships.
      Snakes possess a highly developed vomeronasal system that is used in various
      behaviors such as mating, predator detection, or prey selection, making this
      group a suitable model for study of the vomeronasal chemoreception. In this work,
      we used a proteomics approach to identify and characterize proteins from frog
      cutaneous mucus proteome involved in prey recognition by snakes of the genus
      Thamnophis. Herein we report the purification and characterization of two
      proteins isolated from the frog skin secretome that elicit the vomeronasal organ
      mediated predatory behavior of Thamnophis marcianus. These proteins are members
      of the parvalbumin family, which are calcium-binding proteins generally
      associated to muscular and nervous tissues. This is the first report that
      demonstrates parvalbumins are not strictly restricted to intracellular
      compartments and can also be isolated from exocrine secretions. Purified
      parvalbumins from frog muscle and mucus revealed identical chemoattractive
      properties for T. marcianus. Snake bioassay revealed the Ca(2+)/Mg(2+) dependence
      of the bioactivity of parvalbumins. So parvalbumins appear to be new candidate
      ligands of the vomeronasal organ.

PMID- 16899540
TI  - Unusual N-glycan structures in alpha-mannosidase II/IIx double null embryos
      identified by a systematic glycomics approach based on two-dimensional LC mapping
      and matrix-dependent selective fragmentation method in MALDI-TOF/TOF mass
      spectrometry.
AB  - alpha-Mannosidase IIx (MX) is an enzyme closely related to alpha-mannosidase II
      (MII), a key enzyme in N-glycan biosynthesis that catalyzes the first step in
      conversion of hybrid- to complex-type N-glycans in Golgi apparatus. Recently we
      generated MII/MX double knock-out mice and found that double nulls completely
      lack the complex-type N-glycans (Akama, T. O., Nakagawa, H., Wong, N. K., Sutton
      Smith, M., Dell, A., Morris, H. R., Nakayama, J., Nishimura, S.-I., Pai, A.,
      Moremen, K. W., Marth, J. D., and Fukuda, M. N. (2006) Essential and mutually
      compensatory roles of alpha-mannosidase II and alpha-mannosidase IIx in N-glycan
      processing in vivo in mice. Proc. Natl. Acad. Sci. U. S. A. 103, 8983-8988). In
      the present study, we determined minor but unusual N-glycan structures found in
      MII/MX double knock-out mice. We identified such N-glycans by a systematic
      glycomics approach applying a two-dimensional LC mapping database and matrix
      dependent selective fragmentation technique in MALDI-TOF/TOF MS, a highly
      sensitive and reliable technique that provides specific fragmentations enabling
      the determination of precise oligosaccharide structures including regioisomers
      (Kurogochi, M., and Nishimura, S.-I. (2004) Structural characterization of N
      glycopeptides by matrix-dependent selective fragmentation of MALDI-TOF/TOF tandem
      mass spectrometry. Anal. Chem. 76, 6097-6101). Quantitative profiling of all N
      glycan structures including minor components from MII/MX nulls, MII nulls, MX
      nulls, and wild-type mice at embryonic day 15.5 yielded a total of 37 species
      when structural heterogeneity was reduced by the removal of the sialic acids.
      Among six unusual N-glycan structures, two glycoforms were novel and were found
      only in MII/MX double nulls. We characterize such structure as pseudocomplex-type
      N-glycans. The present study demonstrated that use of the versatile matrix
      dependent selective fragmentation method in MALDI-TOF/TOF MS greatly accelerates
      detailed structural analysis of a trace amount of N-glycans.

PMID- 16899541
TI  - LC-MS/MS analysis of apical and basolateral plasma membranes of rat renal
      collecting duct cells.
AB  - We used biotinylation and streptavidin affinity chromatography to label and
      enrich proteins from apical and basolateral membranes of rat kidney inner
      medullary collecting ducts (IMCDs) prior to LC-MS/MS protein identification. To
      enrich apical membrane proteins and bound peripheral membrane proteins, IMCDs
      were perfusion-labeled with primary amine-reactive biotinylation reagents at 2
      degrees C using a double barreled pipette. The perfusion-biotinylated proteins
      and proteins bound to them were isolated with CaptAvidin-agarose beads, separated
      with SDS-PAGE, and sliced into continuous gel pieces for LC-MS/MS protein
      identification (LTQ, Thermo Electron Corp.). 17 integral and
      glycosylphosphatidylinositol (GPI)-linked membrane proteins and 44 non-integral
      membrane proteins were identified. Immunofluorescence confocal microscopy
      confirmed ACVRL1, H(+)/K(+)-ATPase alpha1, NHE2, and TauT expression in the
      IMCDs. Basement membrane and basolateral membrane proteins were biotinylated via
      incubation of IMCD suspensions with biotinylation reagents on ice. 23 integral
      and GPI-linked membrane proteins and 134 non-integral membrane proteins were
      identified. Analyses of non-integral membrane proteins preferentially identified
      in the perfusion-biotinylated and not in the incubation-biotinylated IMCDs
      revealed protein kinases, scaffold proteins, SNARE proteins, motor proteins,
      small GTP-binding proteins, and related proteins that may be involved in
      vasopressin-stimulated AQP2, UT-A1, and ENaC regulation. A World Wide Web
      accessible database was constructed of 222 membrane proteins (integral and GPI
      linked) from this study and prior studies.

PMID- 16899542
TI  - Disease state differentiation and identification of tuberculosis biomarkers via
      native antigen array profiling.
AB  - A critical element of tuberculosis control is early and sensitive diagnosis of
      infection and disease. Our laboratories recently showed that different stages of
      disease were distinguishable via two-dimensional Western blot analyses of
      Mycobacterium tuberculosis culture filtrate proteins. However, this methodology
      is not suitable for high throughput testing. Advances in protein microarray
      technology provide a realistic mechanism to screen a large number of serum
      samples against thousands of proteins to identify biomarkers of disease states.
      Techniques were established for separation of native M. tuberculosis cytosol and
      culture filtrate proteins, resulting in 960 unique protein fractions that were
      used to generate protein microarrays. Evaluation of serological reactivity from
      42 patients in three tuberculosis disease states and healthy purified protein
      derivative-positive individuals demonstrated that human immunodeficiency virus
      (HIV)-negative cavitary and noncavitary tuberculosis (TB) patients' sera
      recognized 126 and 59 fractions, respectively. Sera from HIV patients coinfected
      with TB recognized 20 fractions of which five overlapped with those recognized by
      non-HIV TB patients' sera and 15 were unique to the HIV+TB+ disease state.
      Identification of antigens within the reactive fractions yielded 11 products
      recognized by both cavitary and noncavitary TB patients' sera and four proteins
      (HspX, MPT64, PstS1, and TrxC) specific to cavitary TB patients. Moreover four
      novel B cell antigens (BfrB, LppZ, SodC, and TrxC) of human tuberculosis were
      identified.

PMID- 16899543
TI  - Epigenetic properties of white-opaque switching in Candida albicans are based on
      a self-sustaining transcriptional feedback loop.
AB  - White-opaque switching in the human fungal pathogen Candida albicans is an
      alternation between two distinct types of cells, white and opaque. White and
      opaque cells differ in their appearance under the microscope, the genes they
      express, their mating behaviors, and the host tissues for which they are best
      suited. Each state is heritable for many generations, and switching between
      states occurs stochastically, at low frequency. In this article, we identify a
      master regulator of white-opaque switching (Wor1), and we show that this protein
      is a transcriptional regulator that is needed to both establish and maintain the
      opaque state. We show that in opaque cells, Wor1 forms a positive feedback loop:
      It binds its own DNA regulatory region and activates its own transcription
      leading to the accumulation of high levels of Wor1. We further show that this
      feedback loop is self-sustaining: Once activated, it persists for many
      generations. We propose that this Wor1 feedback loop accounts, at least in part,
      for the heritability of the opaque state. In contrast, white cells (and their
      descendents) lack appreciable levels of Wor1, and the feedback loop remains
      inactive. Thus, this simple model can account for both the heritability of the
      white and opaque states and the stochastic nature of the switching between them.

PMID- 16899545
TI  - Noninvasive positive-pressure ventilation in ALS: predictors of tolerance and
      survival.
AB  - OBJECTIVE: To identify factors associated with tolerance and survival after
      noninvasive positive-pressure ventilation (NIPPV) and to investigate the
      influence of NIPPV on lung function in patients with ALS. METHODS: NIPPV was
      offered to 71 patients with ALS in accordance with currently published
      guidelines. Effects of NIPPV on lung function and factors influencing tolerance
      and survival after NIPPV were studied. RESULTS: Forty-four patients (61.9%; 95%
      CI: 50.6 to 73.2) tolerated NIPPV (NIPPV use >or=4 h/day) and 27 (38.1%; 95% CI:
      26.8 to 49.4) were intolerant (NIPPV use <4 h/day). Patients with mild or
      moderate bulbar symptoms were more likely to tolerate NIPPV than those with
      severe impairment (odds ratio = 6.09, 95% CI: 1.18 to 31.52, p = 0.031). After
      NIPPV introduction, a slower decline in forced vital capacity (FVC) was observed
      in tolerant vs intolerant patients (p = 0.002). The slope of FVC decline after
      NIPPV initiation (risk ratio [RR]: 0.78, 95% CI: 0.65 to 0.94, p = 0.01) together
      with NIPPV tolerance (RR: 0.32, 95% CI: 0.13 to 0.78, p = 0.013) were the only
      independent predictors of survival in the overall group of patients. In
      multivariate analysis, body mass index was the most powerful predictor of longer
      survival after NIPPV in tolerant patients (RR: 0.77, 95% CI: 0.61 to 0.96, p =
      0.022). CONCLUSION: Survival after noninvasive ventilation was independently
      related to ventilatory use (>or=4 h/day) and to the modifications of forced vital
      capacity decline after treatment initiation. The severity of bulbar impairment
      and the nutritional status of the ALS patients at the introduction of ventilation
      may predict tolerance and survival.

PMID- 16899544
TI  - Inhibition of protein aggregation in vitro and in vivo by a natural
      osmoprotectant.
AB  - Small organic molecules termed osmolytes are harnessed by a variety of cell types
      in a wide range of organisms to counter unfavorable physiological conditions that
      challenge protein stability and function. Using a well characterized reporter
      system that we developed to allow in vivo observations, we have explored how the
      osmolyte proline influences the stability and aggregation of a model aggregation
      prone protein, P39A cellular retinoic acid-binding protein. Strikingly, we find
      that the natural osmolyte proline abrogates aggregation both in vitro and in vivo
      (in an Escherichia coli expression system). Importantly, proline also prevented
      aggregation of constructs containing exon 1 of huntingtin with extended
      polyglutamine tracts. Although compatible osmolytes are known to stabilize the
      native state, our results point to a destabilizing effect of proline on partially
      folded states and early aggregates and a solubilizing effect on the native state.
      Because proline is believed to act through a combination of solvophobic backbone
      interactions and favorable side-chain interactions that are not specific to a
      particular sequence or structure, the observed effect is likely to be general.
      Thus, the osmolyte proline may be protective against biomedically important
      protein aggregates that are hallmarks of several late-onset neurodegenerative
      diseases including Huntington's, Alzheimer's, and Parkinson's. In addition, these
      results should be of practical importance because they may enable protein
      expression at higher efficiency under conditions where aggregation competes with
      proper folding.

PMID- 16899546
TI  - The hunt for an alternate way to generate NAADP. Focus on "NAADP as a second
      messenger: neither CD38 nor base-exchange reaction are necessary for in vivo
      generation of NAADP in myometrial cells".

PMID- 16899548
TI  - Role of cardiolipin alterations in mitochondrial dysfunction and disease.
AB  - Cardiolipin (CL) is a structurally unique dimeric phospholipid localized in the
      inner mitochondrial membrane where it is required for optimal mitochondrial
      function. In addition to its role in maintaining membrane potential and
      architecture, CL is known to provide essential structural and functional support
      to several proteins involved in mitochondrial bioenergetics. A loss of CL
      content, alterations in its acyl chain composition, and/or CL peroxidation have
      been associated with mitochondrial dysfunction in multiple tissues in a variety
      of pathological conditions, including ischemia, hypothyroidism, aging, and heart
      failure. Recently, aberrations in CL metabolism have been implicated as a primary
      causative factor in the cardioskeletal myopathy known as Barth syndrome,
      underscoring an important role of CL in human health and disease. The purpose of
      this review is to provide an overview of evidence that has linked changes in the
      CL profile to mitochondrial dysfunction in various pathological conditions. In
      addition, a brief overview of CL function and biosynthesis, and a discussion of
      methods used to examine CL in biological tissues are provided.

PMID- 16899547
TI  - Characterization of a novel voltage-dependent outwardly rectifying anion current
      in Caenorhabditis elegans oocytes.
AB  - An inwardly rectifying swelling- and meiotic cell cycle-regulated anion current
      carried by the ClC channel splice variant CLH-3b dominates the whole cell
      conductance of the Caenorhabditis elegans oocyte. Oocytes also express a novel
      outwardly rectifying anion current termed I(Cl,OR). We recently identified a worm
      strain carrying a null allele of the clh-3 gene and utilized oocytes from these
      animals to characterize I(Cl,OR) biophysical properties. The I(Cl,OR) channel is
      strongly voltage dependent. Outward rectification is due to voltage-dependent
      current activation at depolarized voltages and rapid inactivation at voltages
      more hyperpolarized than approximately +20 mV. Apparent channel open probability
      is zero at voltages less than +20 mV. The channel has a 4:1 selectivity for Cl(-)
      over Na(+) and an anion selectivity sequence of SCN(-) > I(-) > Br(-) > Cl(-) >
      F(-). I(Cl,OR) is relatively insensitive to most conventional anion channel
      inhibitors including DIDS, 4,4'-dinitrostilbene-2,2'-disulfonic acid, 9
      anthracenecarboxylic acid, and 5-nitro-2-(3-phenylpropylamino)benzoic acid.
      However, the current is rapidly inhibited by niflumic acid, metal cations
      including Gd(3+), Cd(2+), and Zn(2+), and bath acidification. The combined
      biophysical properties of I(Cl,OR) are distinct from those of other anion
      currents that have been described. During oocyte meiotic maturation, I(Cl,OR)
      activity is rapidly downregulated, suggesting that the channel may play a role in
      oocyte Cl(-) homeostasis, development, cell cycle control, and/or ovulation.

PMID- 16899549
TI  - Cell and animal models of mtDNA biology: progress and prospects.
AB  - The past two decades have witnessed an evolving understanding of the
      mitochondrial genome's (mtDNA) role in basic biology and disease. From the
      recognition that mutations in mtDNA can be responsible for human disease to
      recent efforts showing that mtDNA mutations accumulate over time and may be
      responsible for some phenotypes of aging, the field of mitochondrial genetics has
      greatly benefited from the creation of cell and animal models of mtDNA mutation.
      In this review, we critically discuss the past two decades of efforts and
      insights gained from cell and animal models of mtDNA mutation. We attempt to
      reconcile the varied and at times contradictory findings by highlighting the
      various methodologies employed and using human mtDNA disease as a guide to better
      understanding of cell and animal mtDNA models. We end with a discussion of
      scientific and therapeutic challenges and prospects for the future of mtDNA
      transfection and gene therapy.

PMID- 16899550
TI  - Glucosamine protects neonatal cardiomyocytes from ischemia-reperfusion injury via
      increased protein-associated O-GlcNAc.
AB  - Increased levels of protein O-linked N-acetylglucosamine (O-GlcNAc) have been
      shown to increase cell survival following stress. Therefore, the goal of this
      study was to determine whether in isolated neonatal rat ventricular myocytes
      (NRVMs) an increase in protein O-GlcNAcylation resulted in improved survival and
      viability following ischemia-reperfusion (I/R). NRVMs were exposed to 4 h of
      ischemia and 16 h of reperfusion, and cell viability, necrosis, apoptosis, and O
      GlcNAc levels were assessed. Treatment of cells with glucosamine, hyperglycemia,
      or O-(2-acetamido-2-deoxy-D-glucopyranosylidene)-amino-N-phenylcarbamate(PUGNAc),
      an inhibitor of O-GlcNAcase, significantly increased O-GlcNAc levels and improved
      cell viability, as well as reducing both necrosis and apoptosis compared with
      untreated cells following I/R. Alloxan, an inhibitor of O-GlcNAc transferase,
      markedly reduced O-GlcNAc levels and exacerbated I/R injury. The improved
      survival with hyperglycemia was attenuated by azaserine, which inhibits glucose
      metabolism via the hexosamine biosynthesis pathway. Reperfusion in the absence of
      glucose reduced O-GlcNAc levels on reperfusion compared with normal glucose
      conditions and decreased cell viability. O-GlcNAc levels significantly correlated
      with cell viability during reperfusion. The effects of glucosamine and PUGNAc on
      cellular viability were associated with reduced calcineurin activation as
      measured by translocation of nuclear factor of activated T cells, suggesting that
      increased O-GlcNAc levels may attenuate I/R induced increase in cytosolic Ca(2+).
      These data support the concept that activation of metabolic pathways leading to
      an increase in O-GlcNAc levels is an endogenous stress-activated response and
      that augmentation of this response improves cell survival. Thus strategies
      designed to activate these pathways may represent novel interventions for
      inducing cardioprotection.

PMID- 16899552
TI  - Role of protein phosphatase 2A in calcium-dependent chloride secretion by human
      colonic epithelial cells.
AB  - EGF inhibits carbachol-induced chloride secretion by regulating a basolateral
      potassium channel via phosphatidylinositol 3-kinase (PI 3-kinase) and PKCepsilon
      activation. Although both EGF and carbachol cause tyrosine phosphorylation of p85
      of PI 3-kinase, only EGF activates the enzyme. Serine phosphorylation of p85 is
      thought to suppress the lipid kinase of PI 3-kinase. Our present study examined
      whether the differential effects of carbachol and EGF on PI 3-kinase activity
      correspond to varying phosphorylation of p85, and the mechanisms and
      consequences. T(84) colonic epithelial cells were treated with either EGF or
      carbachol. Cell lysates were immunoprecipitated with p85 antibody and blotted
      with either phosphotyrosine or phosphoserine antibodies. Protein phosphatase (PP)
      1 and 2A activities were also measured. Both tyrosine and serine residues of p85
      were phosphorylated by carbachol, whereas EGF induced only tyrosine
      phosphorylation. Moreover, EGF abolished carbachol-induced serine phosphorylation
      of p85 and activated PP2A without affecting PP1. Carbachol did not affect either
      phosphatase. Calyculin A or okadaic acid pretreatment reversed the inhibitory
      action of EGF on carbachol-induced chloride secretion and restored serine
      phosphorylation of p85. Although carbachol recruits p85, it phosphorylates both
      serine and tyrosine residues so that the lipid kinase of PI 3-kinase is
      inhibited. EGF results in p85 tyrosine phosphorylation as well as
      dephosphorylation of serine residues via the activation of PP2A. This explains
      the differential induction of PI 3-kinase enzyme activity in response to EGF
      and/or carbachol and has functional implications. Our data provide further
      insights into negative signals that regulate chloride secretion and into the
      molecular basis of signaling diversification in the intestinal epithelium.

PMID- 16899551
TI  - Cellular mechanisms underlying prostaglandin-induced transient cAMP signals near
      the plasma membrane of HEK-293 cells.
AB  - We have previously used cyclic nucleotide-gated (CNG) channels as sensors to
      measure cAMP signals in human embryonic kidney (HEK)-293 cells. We found that
      prostaglandin E(1) (PGE(1)) triggered transient increases in cAMP concentration
      near the plasma membrane, whereas total cAMP levels rose to a steady plateau over
      the same time course. In addition, we presented evidence that the decline in the
      near-membrane cAMP levels was due primarily to a PGE(1)-induced stimulation of
      phosphodiesterase (PDE) activity, and that the differences between near-membrane
      and total cAMP levels were largely due to diffusional barriers and differential
      PDE activity. Here, we examine the mechanisms regulating transient, near-membrane
      cAMP signals. We observed that 5-min stimulation of HEK-293 cells with
      prostaglandins triggered a two- to threefold increase in PDE4 activity.
      Extracellular application of H89 (a PKA inhibitor) inhibited stimulation of PDE4
      activity. Similarly, when we used CNG channels to monitor cAMP signals we found
      that both extracellular and intracellular (via the whole-cell patch pipette)
      application of H89, or the highly selective PKA inhibitor, PKI, prevented the
      decline in prostaglandin-induced responses. Following pretreatment with rolipram
      (a PDE4 inhibitor), H89 had little or no effect on near-membrane or total cAMP
      levels. Furthermore, disrupting the subcellular localization of PKA with the A
      kinase anchoring protein (AKAP) disruptor Ht31 prevented the decline in the
      transient response. Based on these data we developed a plausible kinetic model
      that describes prostaglandin-induced cAMP signals. This model has allowed us to
      quantitatively demonstrate the importance of PKA-mediated stimulation of PDE4
      activity in shaping near-membrane cAMP signals.

PMID- 16899553
TI  - Gap junction channel activity in short-term cultured human detrusor myocyte cell
      pairs: gating and unitary conductances.
AB  - Several independent lines of investigation indicate that intercellular
      communication through gap junctions modulates bladder physiology and, moreover,
      that altered junctional communication may contribute to detrusor overactivity.
      However, as far as we are aware, there are still no direct recordings of gap
      junction-mediated intercellular currents between human or rat detrusor myocytes.
      Northern and Western blots were used to identify connexin expression in frozen
      human bladder tissue and short-term cultured human detrusor myocytes. Double
      whole cell patch (DWCP) recording revealed that human detrusor myocyte cell pairs
      were well coupled with an average junctional conductance of 6.5 +/- 4.6 nS
      (ranging from 0.1 to 15 nS, n = 22 cell pairs). Macroscopic gap junction channel
      currents in human detrusor myocytes exhibited voltage dependence similar to
      homotypic connexin43. The normalized transjunctional conductance-voltage (G(j)
      V(j)) relationship was symmetrical and well described by a two-state Boltzmann
      relation (G(min) approximately 0.33, V(0) = 63.6 mV, Z = 0.117 or equal to 2.95
      gating charges), suggestive of a bilateral voltage-gated mechanism. In symmetric
      165 mM CsCl, the measured single-channel slope conductance was approximately 120
      pS for the fully open channel and approximately 26 pS for the major substate.
      Occasionally, other subconductance states were also observed. The single-channel
      mean open time declined with increasing V(j), accounting for the V(j)-dependent
      decline of macroscopic junctional current. Qualitatively similar
      electrophysiological characteristics were observed in DWCP of freshly isolated
      rat detrusor myocytes. These data confirm and extend previous observations and
      are consistent with reports in other smooth muscle cells types in which Cx43
      mediated intercellular communication has been identified.

PMID- 16899554
TI  - Endocrine signaling in Caenorhabditis elegans controls stress response and
      longevity.
AB  - Modulation of insulin/IGF signaling in the nematode Caenorhabditis elegans is the
      central determinant of the endocrine control of stress response, diapause, and
      aging. Mutations in many genes that interfere with, or are controlled by, insulin
      signaling have been identified in the last decade by genetic analyses in the
      worm. Most of these genes have orthologs in vertebrate genomes, and their
      functional characterization has provided multiple hints about conserved
      mechanisms for the genetic influence on aging. The emerging picture is that
      insulin-like molecules, through the activity of the DAF-2/insulin/ IGF-I-like
      receptor, and the DAF-16/FKHRL1/FOXO transcription factor, control the ability of
      the organism to deal with oxidative stress, and interfere with metabolic programs
      that help to determine lifespan.

PMID- 16899555
TI  - Effect of periconceptional undernutrition and gender on hypothalamic-pituitary
      adrenal axis function in young adult sheep.
AB  - Glucocorticoids are proposed to act as intermediary factors that transcribe the
      developmental programming sequelae of maternal nutrient restriction (NR).
      Periconceptional under-nutrition of sheep markedly activates fetal hypothalamic
      pituitary-adrenal (HPA) axis activity leading to preterm birth, while transient
      undernutrition during late gestation in sheep programs adult HPA axis function.
      To date, no study has examined resting or stimulated HPA axis function in young
      adult offspring following a periconceptional nutritional challenge. In the
      present study, 20 ewes were either periconceptionally undernourished (50%
      metabolisable energy requirements from days 1 to 30 gestation; NR, n = 8) or fed
      to control levels (100% requirement; controls, n = 12) to term (147 days
      gestation). Ewes were blood sampled remotely at 2 and 30 days using automated
      blood sampling equipment. Thereafter, offspring (controls, n = 6/6 males/females;
      NR, n = 4/4 males/females) were reared to 1 year of age and on separate days
      received either an i.v. corticotrophin-releasing hormone (CRH; 0.5 microg/kg) and
      vasopressin (AVP; 0.1 microg/kg) challenge or a synthetic ACTH i.v. bolus
      (Synacthen; 1.25 microg/kg), and blood samples were taken (manually and remotely)
      at appropriate intervals for measurement of plasma ACTH and cortisol accordingly.
      Resting plasma cortisol, assessed remotely, was similar in ewes during
      undernutrition (control 18.3 +/- 1.4 vs NR 23.4 +/- 1.9 nmol/l) and in offspring
      at 4 months of age (control male 17.6 +/- 2.9; control female 17.2 +/- 0.4, NR
      male 16.5 +/- 3.1, NR female 21.7 +/- 4.0 nmol/l). At 12 months of age, however,
      resting plasma cortisol was significantly increased in NR females (control male
      28.0 +/- 1.5, control female 32.9 +/- 9, NR male 32 +/- 7, NR female 53 +/- 10
      nmol/l, F 5.7, P = 0.02) despite no difference in plasma ACTH concentration.
      There was an interaction between nutritional group and gender for both the
      pituitary and adrenal responses to CRH and AVP, i.e. for controls, females
      exhibited increased plasma ACTH or cortisol relative to males but for NR this
      trend was either not present or reversed. The adrenocortical response to
      synthetic ACTH was gender-dependent only, being greater in female offspring.
      Combined CRH and AVP provoked a transient hypertension and marked bradycardia in
      all animals, irrespective of dietary group or gender and could be effectively
      reproduced by an AVP bolus alone. In conclusion, the present study has shown that
      periconceptional undernutrition of sheep has only a minor influence on HPA axis
      function in their young adult offspring when considered alongside the effect of
      gender per se.

PMID- 16899556
TI  - Centrally administered neuropeptide W-30 activates magnocellular neurosecretory
      cells in the supraoptic and paraventricular nuclei with neurosecretion in rats.
AB  - We examined the effects of i.c.v. administration of neuro-peptide W-30 (NPW30) on
      plasma arginine vasopressin (AVP) and plasma oxytocin (OXT) using RIA. The
      induction of c-fos mRNA, AVP heteronuclear (hn)RNA, and c-Fos protein (Fos) in
      the supraoptic nucleus (SON) and paraventricular nucleus (PVN) of rats were also
      investigated using in situ hybridization histochemistry for c-fos mRNA and AVP
      hnRNA, and immunohistochemistry for Fos. Both plasma AVP and OXT were
      significantly increased at 5 and 15 min after i.c.v. administration of NPW30 (2.8
      nmol/rat). In situ hybridization histochemistry revealed that the induction of c
      fos mRNA and AVP hnRNA in the SON and PVN were significantly increased 15, 30,
      and 60 min after i.c.v. administration of NPW30 (1.4 nmol/rat). Dual
      immunostaining for Fos/AVP and Fos/OXT revealed that both AVP-like immunoreactive
      (LI) cells and OXT-LI cells exhibited nuclear Fos-LI in the SON and PVN, 90 min
      after i.c.v. administration of NPW30 (2.8 nmol/rat). These results suggest that
      central NPW30 may be involved in the regulation of secretion of AVP and OXT in
      the magnocellular neurosecretory cells in the SON and PVN.

PMID- 16899557
TI  - Estrogen-triggered delays in mammary gland gene expression during the estrous
      cycle: evidence for a novel timing system.
AB  - During the estrous cycle and beginning in estrus, the mammary gland undergoes
      pregnancy-like development that depends on transcriptional regulation by the
      estrogen and progesterone receptors (ER, PR) and Pax-2 as well as the action of
      the growth factors Wnt-4 and RANKL. In this report, we first describe the decay
      and delayed expression of ERalpha, PR, and Pax-2 proteins as well as depression
      of Wnt-4 and RANKL mRNA coincident with the strong estrogen surge in proestrus.
      In time-course studies using ovari-ectomized mice, a single estrogen injection
      replicated these delays and caused an 18 h delay in Wnt-4 expression. Molecular
      time-delay systems are at the core of cellular cycles, most notably the circadian
      clock, and depend on proteasome degradation of transcriptional regulators that
      exhibit dedicated timing functions. The cytoplasmic dynamics of these regulators
      govern delay duration through negative transcription/translation feedback loops.
      A proteasome inhibitor, PS-341, blocked estrogen-stimulated ERalpha, PR, and Pax
      2 decay and proteasome chymotryptic activity, assayed using a fluorogenic
      substrate, was elevated in proestrus correlating with the depletion of the
      transcription factors. The 18-h delay in Wnt-4 induction corresponded to the
      turnover time of Pax-2 protein in the cytoplasm and was eliminated in Pax-2
      knockout mammary tissue, demonstrating that Pax-2 has a unique timing function.
      The patterns of estrogen-triggered ERalpha, PR, and Pax-2 turnover were
      consistent with a negative transcriptional feedback. Retarding the expression of
      ERalpha, PR, and Pax-2 may optimize preparations for pregnancy by coordinating
      expression of critical receptors and transcription factors with rising estrogen
      and progesterone levels in estrus. The estrogen surge in proestrus has no defined
      mammotropic function. This study provides the first evidence that it is a
      synchronizing signal triggering proteasome-dependent turnover of mammary gland
      ERalpha, PR, and Pax-2. We hypothesize that the delays reflect a previously
      unrecognized timing system, which is present in all ovarian target tissues.

PMID- 16899558
TI  - Estrogen induces angiogenesis of the female rabbit bladder.
AB  - Postmenopausal bladder dysfunction has been speculated to involve decreased
      circulating estrogen levels. It is our hypothesis that estrogen induces bladder
      dysfunctions by modulating blood flow to the bladder, i.e. low estrogen reduces
      blood flow to the bladder, whereas high estrogen increases blood flow. Our
      previous studies have demonstrated that estrogen administration in female rabbits
      induces a 'functional hypertrophy' of the urinary bladder smooth muscle
      represented by increased smooth muscle mass, which corresponds to increased
      contractile responses to all forms of stimulation. The present study investigates
      the effect of estrogen on vasculature density and distribution. Twenty-four
      female New Zealand white rabbits were separated into six groups of four rabbits
      each. Group 1 served as controls. Groups 2-6 were ovariectomized. Two weeks after
      ovariectomy (Ovx), groups 3-6 were given 17-beta estradiol (1 mg/kg per day) by
      s.c. implant for 1, 3, 7, and 14 days respectively. Blood vessel density and
      distribution were evaluated by immunohistochemistry and quantitative image
      analyses. Ovx resulted in significant vascular degeneration and decreased
      density, whereas estradiol administration mediated a significant angiogenic
      effect characterized by increased vascular density, and distribution of new
      vasculature within the smooth muscle bundles of the detrusor. Estradiol-induced
      vasculogenesis corresponds with our previously demonstrated increase in blood
      flow to the bladder and increased contractility. The most interesting aspect of
      these studies is the increased vascularization localized within the muscle
      bundles rather than between the muscle bundles, which may be important in the
      link between estrogen and increased incidence of cancers.

PMID- 16899559
TI  - Cell-surface expression, progestin binding, and rapid nongenomic signaling of
      zebrafish membrane progestin receptors alpha and beta in transfected cells.
AB  - Recently, a unique family of membrane progestin receptors (mPRalpha, mPRbeta, and
      mPRgamma) was identified, which may be responsible for mediating rapid,
      nongenomic actions of progestins in a variety of target tissues. In this study,
      the mPRalpha and mPRbeta isoforms from zebrafish were shown to be rapidly and
      specifically activated by the maturation-inducing steroid (MIS) of this species,
      4-pregnen-17,20beta-diol-3-one (17,20beta-DHP). The zebrafish mPRalpha and a
      previously uncharacterized mPRbeta isoform were stably expressed in nuclear
      progesterone receptor-deficient mammalian breast cancer cells, MDA-MB-231.
      Expression and surface localization of the receptors were verified by flow
      cytometry, biotin surface labeling, and Western blotting. Plasma membrane
      proteins from mPRalpha- or mPRbeta-transfected cells showed high affinity
      (mPRalpha, K(d) 7 nM; mPRbeta, K(d) 12 nM), saturable, displaceable, single
      binding sites specific for 17,20beta-DHP, whereas negligible specific 17,20beta
      DHP binding was observed in nontransfected cells. Progestin treatment caused
      significant activation of mitogen-activated protein kinase (MAPK) within 5 min in
      cells transfected with either of the receptors as measured by western blotting
      and flow cytometry. The rank order of the potencies of several progestins in
      activating MAPK via mPRalpha and mPRbeta was the same (17,20beta-DHP>progesterone
      >4-pregnen-17,20beta,21-triol-3-one). Interestingly, the MIS in zebrafish,
      17,20beta-DHP, was also the most potent inhibitor, among the progestins tested,
      of adenylyl cyclase activity in cells transfected with either of the receptors.
      This progestin significantly decreased cAMP levels in both mPRalpha- and mPRbeta
      transfected cells in a dose-responsive and time-dependent manner. In addition,
      signaling of the zebrafish mPRalpha was blocked by pertussis toxin, implying
      activation of a G(i) protein, while sensitivity to pertussis or cholera toxin was
      not shown with mPRbeta-mediated signaling, possibly indicating that this receptor
      activates a different pertussis toxin-insensitive G protein. The results of this
      study suggest that zebrafish mPRalpha and mPRbeta signal similarly upon progestin
      binding resulting in rapid activation of MAPK and downregulation of adenylyl
      cyclase activity.

PMID- 16899560
TI  - Effect of age on progesterone receptor expression, and osteoprogenitor
      proliferation and differentiation in female rat vertebral cell populations.
AB  - In the present investigation, we evaluated whether the capacity for proliferation
      and differentiation of progesterone (Prog)-dependent osteoprogenitors in the
      female rat skeleton is related to the level of Prog receptors (PRs) and/or the
      level of circulating estrogen. We confirmed that in rats, estrogen levels at 18
      months of age are higher than those at 3 months, and higher again in rats of
      22.5, 25.5, and 26 months of age. Prog levels in rats of ages between 18 and 25.5
      months were lower than those at 26 and 3 months of age. PR-A levels were tenfold
      higher than those of PR-B in cell populations where PR-B was detectable; PR-B
      receptors were not detectable in all cell populations. In populations derived
      from 22.5 to 26 months old rats, the basal levels of PR-A were higher than those
      derived from 3 and 18 months old rats by five- and twofold respectively. Prog
      treatment enhanced PR-A expression in animals of all ages. Estrogen enhanced the
      effect of Prog on PR-A expression in cell populations from the 3 and 18 months
      old rats, but had no effect on PR-A expression in cell populations from 22.5,
      25.5, and 26 months old rats. This might be related to the high basal expression
      of PR in 22.5-26 months old rats (the 'persistent estrous' phase). Our results
      also confirm our previous observation that in rats, the number of Prog- and
      dexamethasone (Dex)- dependent osteoprogenitors, and the effect of estrogen on
      the response to Prog do not decrease with age. In conclusion, we have shown that
      the basal level of PR-A was increased in old rats, and that this correlated with
      increased serum estrogen levels, but not with the number of detectable Prog
      dependent osteoprogenitors. We also found that Prog upregulates the expression of
      its own receptors and that estrogen enhances this in young rats but not in rats
      over 22.5 months of age, in which estrogen levels are elevated.

PMID- 16899561
TI  - Local over-expression of prolactin in differentiating mouse mammary gland induces
      functional defects and benign lesions, but no carcinoma.
AB  - Experimental, clinical, and epidemiological data support the growth-promoting
      role of endocrine prolactin (PRL) in mammary tumors. PRL is also produced by the
      breast, where it is now recognized to act as a growth/survival factor via
      autocrine/paracrine mechanisms. Recent transgenic (Tg) mouse models have revealed
      the pro-oncogenic effect of PRL over-expression in virgin mammary glands. To
      address the question whether PRL tumorigenicity was maintained on differentiated
      mammary glands, we generated mammary-specific Tg mice expressing human (h)PRL
      under the control of the milk whey acidic protein promoter, which directs
      autocrine hPRL over-expression in late gestation throughout lactation. Minimal
      levels of transgene expression were detected in the mammary glands of virgin
      animals, which at best induced partial ductal branching and lobulo-alveolar
      structures in older nulliparous females. As expected, expression of mammary hPRL
      dramatically increased at the end of first pregnancy, and from this point it
      never returned to baseline, although it peaked at each gestation/lactation cycle.
      Over-expression of hPRL that starts when the gland is already well into the
      differentiation process led to various morphological mammary alterations,
      including abnormally differentiated epithelium, atropy of the myoepithelial
      layer, dilated ducts, cysts, and lymphocytic infiltrates. These phenotypes tended
      to worsen with successive pregnancies, also reflecting cumulative damage of
      failure of involution. Although some older, multiparous females developed benign
      tumors (papillomas and metaplasias), none of the animals studied developed
      mammary carcinomas. In addition, we noticed that half of the Tg females exhibited
      lactation defects, leading to significantly increased pup mortality. This
      phenotype was due neither to failure of milk production nor to modification of
      its protein content, but rather it was correlated to lipid enrichment of the
      milk, which, in combination with profoundly altered morphology of the gland, led
      to impaired milk extrusion through the nipple. In summary, these data show that
      over-expression of autocrine hPRL in a differentiating mammary gland induces
      dramatic functional and morphological defects, but not carcinoma. This deserves
      further investigations on the emerging concept that autocrine PRL may have
      different effects on pathological development of the mammary gland depending on
      the differentiation state of the latter.

PMID- 16899563
TI  - Plasma concentrations of prolactin in brushtail possums (Trichosurus vulpecula)
      in different physiological states.
AB  - Prolactin (Prl) has been implicated in reproduction in many mammalian species and
      is illustrated by the distinctive patterns of secretion during the breeding
      season, the oestrous cycle and lactation. The recent development of a homologous
      RIA for measuring the circulating Prl concentrations in brushtail possums has
      facilitated the reliable measurement of Prl in plasma during different
      physiological states in this species for the first time. Determination of Prl
      concentrations during lactation involved the collection of weekly blood samples
      from eight female possums from the time of parturition through either one or two
      consecutive lactational cycles. Prl was at baseline levels during early lactation
      (weeks 0-14 post-partum), and then increased markedly to maximum concentrations
      at weeks 19-21 before returning to nadir levels at a time coincident with the
      weaning of pouch young (weeks 23-27). The profile of Prl secretion over the
      oestrous cycle and in particular at the time of the preovulatory LH surge was
      obtained from 14 possums during the reproductive cycle, in which preovulatory
      follicle development and ovulation were monitored by laparoscopy. There was no
      distinct daily pattern of Prl secretion during the oestrous cycle; however, in
      3/4 possums in which a typical preovulatory LH surge was measured, a biphasic
      preovulatory Prl surge was also observed. The preovulatory Prl surge commenced 2
      6 h prior to, and had returned to baseline close to the onset of, the
      preovulatory LH surge, and a second surge of Prl occurred concomitantly with the
      delayed preovulatory FSH surge. Seasonality of Prl levels was established from
      weekly blood samples collected from six barren female possums, and concentrations
      of Prl were lower during the breeding season compared to the non-breeding season.
      Additionally, a circadian pattern of Prl secretion was evident in both female and
      male possums, with Prl levels higher in the morning compared to the afternoon. In
      conclusion, interpretation of endogenous secretory patterns suggests that Prl may
      be important during late lactation and at impending ovulation, but the
      involvement of the circannual rhythm of Prl in the regulation of seasonality in
      the brushtail possum remains to be determined.

PMID- 16899562
TI  - Anti-prolactin (PRL) autoantibody-binding sites (epitopes) on PRL molecule in
      macroprolactinemia.
AB  - Macroprolactinemia, in which serum prolactin (PRL) mainly consists of PRL with a
      molecular mass greater than 100 kDa, has been demonstrated to be associated with
      hyperprolactinemia. We previously reported that anti-PRL autoantibody is the
      major cause of macroprolactinemia. In this study, the autoantibody-binding sites
      (epitopes) on the PRL molecule were examined using deletion mutant PRL. The sera
      from 159 patients with hyperprolactinemia were screened for macroprolactinemia
      using the polyethylene glycol method and 18 patients (11%) were diagnosed with
      macroprolactinemia. The sera from these patients were incubated with glutathione
      S-transferase-human prolactin (hPRL) fragment fusion proteins immobilized on
      glutathione sepharose and the amounts of bound immunoglobulin G (IgG) were
      measured using ELISA. IgG was bound to full-length hPRL1-199 in significantly
      greater amounts in sera from 14 of 18 patients with macroprolactinemia than in
      controls. hPRL, but not PRL of other species such as bovine, porcine, rat, or
      human GH, dose-dependently displaced the binding, suggesting that these patients
      had hPRL-specific autoantibodies. Deletion of 34 amino acid residues from N
      and/or C-terminals significantly reduced the binding and N- or C-terminal
      fragment alone showed partial but significant binding, suggesting that the major
      epitopes recognized by anti-PRL autoantibodies are located in both N- and C
      terminal residues of the PRL molecule.

PMID- 16899564
TI  - Prolactin activates mammalian target-of-rapamycin through phosphatidylinositol 3
      kinase and stimulates phosphorylation of p70S6K and 4E-binding protein-1 in
      lymphoma cells.
AB  - Mitogens activate the mammalian target-of-rapamycin (mTOR) pathway through
      phosphatidylinositol 3-kinase (PI3K). The activated mTOR kinase phosphorylates/
      activates ribosomal protein S6 kinase (p70S6K) and phosphorylates/inactivates
      eukaryotic initiation factor 4E-binding protein-1 (4E-BP1), resulting in the
      initiation of translation and cell-cycle progression. The prolactin receptor
      signaling cascade has been implicated in crosstalk with the mTOR pathway, but
      whether prolactin (PRL) directly activates mTOR is not known. This study showed
      that PRL stimulated the phosphorylation of mTOR, p70S6K, Akt, and Jak2 kinases in
      a dose- and time-dependent manner in PRL-dependent rat Nb2 lymphoma cells. PRL
      stimulated phosphorylation of mTOR was detected as early as 10 min, closely
      following the phosphorylation of Akt (upstream of mTOR), but preceding that of
      the downstream p70S6K. PRL activation of mTOR was inhibited by rapamycin (mTOR
      inhibitor), LY249002, and wortmannin (P13K inhibitors), but not by AG490 (Jak2
      inhibitor), indicating that it was mediated by the P13K/Akt, but not Jak2,
      pathway. PRL also stimulated phosphorylation of 4E-BP1 in Nb2 cells. PRL-induced
      phosphorylation of p70S6K and 4E-BP1 was inhibited by rapamycin, but not by
      okadaic acid (inhibitor of protein phosphatase, PP2A). PRL induced a transient
      interaction between p70S6K and the catalytic subunit of PP2A (PP2Ac) in 1 and 2
      h, whereas a PP2Ac-4E-BP1 complex was constitutively present in quiescent and PRL
      treated Nb2 cells. These results suggested that p70S6K and 4E-BP1 were substrates
      of PP2A and the inhibition of mTOR promoted their dephosphorylation by PP2A. In
      summary, PRL-stimulated phosphorylation of mTOR is mediated by PI3K. PRL
      activated mTOR may phosphorylate p70S6K and 4E-BP1 by restraining PP2A.

PMID- 16899565
TI  - Tumor necrosis factor {alpha} reversibly disrupts the blood-testis barrier and
      impairs Sertoli-germ cell adhesion in the seminiferous epithelium of adult rat
      testes.
AB  - The timely restructuring of the blood-testis barrier (BTB) that facilitates the
      migration of preleptotene and leptotene spermatocytes from the basal to the
      adluminal compartment in the seminiferous epithelium of adult rat testes, which
      occurs at late stage VII through early stage VIII of the epithelial cycle, is a
      crucial cellular event of spermatogenesis. However, the regulation of BTB
      dynamics at the biochemical level remains elusive. In this study, tumor necrosis
      factor alpha (TNFalpha), a secretory product of Sertoli and germ cells in rat
      testes, was shown to affect junction dynamics in vivo. Following an acute
      administration of recombinant TNFalpha directly to adult rat testes in vivo at
      0.5 and 2 mug/testis (with a body weight ~300 g), this treatment significantly
      and transiently disrupted the BTB. It also transiently inhibited the steady-state
      protein levels of occludin, zonula occludens-1, and N-cadherin, but not junction
      adhesion molecule-A, alpha-, and beta-catenin in testes at the BTB site as
      illustrated by immunoblottings, immunohistochemistry, electron microscopy, and
      fluorescent microscopy. This transient disruption of the BTB integrity induced by
      TNFalpha treatment was further demonstrated by a functional test to assess the
      passage of a fluorescent dye (e.g. fluorescein-5-isothiocyanate) from the
      systemic circulation to the adluminal compartment. Additionally, both the
      phosphorylated-Ser/Thr protein kinase activated by MAP kinase kinase (p-p38) and
      phosphorylated-externally regulated kinase (p-ERK) mitogen -activated protein
      kinase-signaling pathways were transiently activated. Collectively, these data
      coupled with the recently published in vitro studies have illustrated that the
      BTB is likely utilizing a novel mechanism in which localized production of
      TNFalpha by Sertoli and germ cells into the microenvironment at the basal
      compartment facilitates the timely restructuring ('opening'?) of the BTB during
      spermatogenesis to facilitate germ cell migration.

PMID- 16899566
TI  - Regulated production of activin A and inhibin B throughout the cycle of the
      seminiferous epithelium in the rat.
AB  - Production and regulation of activin A and inhibin B during the cycle of the
      seminiferous epithelium were investigated in adult rats. Immunohistochemistry
      localised the activin beta(A)-subunit to the Sertoli cell cytoplasm, with much
      weaker expression in spermatocytes and spermatids. Both activin A and inhibin B,
      measured by ELISA were secreted by, seminiferous tubule fragments over 72 h in
      culture. Activin A was secreted in a cyclic manner with peak secretion from
      tubules isolated at stage VIII. Tubules collected during stage VI produced the
      least activin A. Inhibin B secretion was highest from stage IX-I tubules and
      lowest from stage VII tubules. Addition of interleukin-1beta (IL-1beta) had
      relatively little effect on activin A or inhibin B secretion in culture. In
      contrast, the peak secretion of activin A by stage VIII tubules was blocked by co
      incubation with an excess of human recombinant IL-1 receptor antagonist, whereas
      inhibin B secretion increased slightly. Dibutyryl cAMP stimulated activin A
      secretion by late stage VII and VIII tubules and stimulated inhibin B across all
      stages. These data indicate that activin A and inhibin B are cyclically regulated
      within the seminiferous epithelium, with endogenous IL-1 (presumably IL-1alpha
      produced by the Sertoli cells), responsible for a peak of activin A production
      subsequent to sperm release at stage VIII. These data provide direct evidence
      that production of activin A and inhibin B by the Sertoli cell is locally
      modulated by IL-1alpha , in addition to FSH/cAMP, under the influence of the
      developing spermatogenic cells.

PMID- 16899567
TI  - G protein-coupled receptor kinase 2 and beta-arrestins are recruited to FSH
      receptor in stimulated rat primary Sertoli cells.
AB  - FSH-receptor (FSH-R) signaling is regulated by agonist-induced desensitization
      and internalization. It has been shown, in a variety of overexpression systems,
      that G protein-coupled receptor kinases (GRKs) phosphorylate the activated FSH-R,
      promote beta-arrestin recruitment and ultimately lead to internalization. The
      accuracy of this mechanism has not yet been demonstrated in cells expressing
      these different molecules at physiological levels. Using sucrose gradient
      fractionation, we show that FSH induces the recruitment of the endogenous GRK 2
      and beta-arrestin 1/2 from the cytoplasm to the plasma membrane of rat primary
      Sertoli cells. As assessed by ligand binding, the FSH-R was found expressed in
      the fractions where GRK 2 and beta-arrestins were recruited upon FSH treatment.
      In addition, the endogenous beta-arrestin 1 was found dephosphorylated in an
      agonist-dependent manner. Finally, a significant FSH-binding activity was co
      immunoprecipitated with the endogenous beta-arrestins from agonist-stimulated but
      not from untreated Sertoli cell extracts. This FSH-R interaction with beta
      arrestins was sustained for up to 30 min. In conclusion, our data strongly
      suggest that the GRK/beta-arrestin machinery plays a physiologically relevant
      role in the regulation of the FSH signaling.

PMID- 16899568
TI  - Extracellular matrix dermatopontin modulates prostate cell growth in vivo.
AB  - Dermatopontin is a tyrosine-rich acidic extracellular matrix protein of 22 kDa
      with possible functions in cell-matrix interactions and matrix assembly. We have
      previously isolated mRNAs expressed in hormone-refractory, but not in hormone
      sensitive, mouse mammary cancer by comparing the mRNAs expressed in either tumor.
      A partial mRNA sequence isolated was later proven to be a part of mouse
      dermatopontin mRNA sequence. Transfectants of mouse dermatopontin cDNA into PC-3
      human prostate cancer cells enhanced tumor growth when those were implanted
      subcutaneously in nude mice compared with the controls. Those transfectants
      showed a prominent stroma compared with the controls. Localization of the targets
      of a fusion protein of mouse dermatopontin and alkaline phosphatase was in the
      stroma of the PC-3 tumor tissues, but not in the tumor cells themselves.
      Additionally, we have established mouse dermatopontin transgenic mice under the
      control of the rat probasin promoter. The prostatic dorsal lobes of dermatopontin
      transgenic mouse showed prostate intra-epithelial neoplasia at the age of 11
      months, but the control littermates did not. Epithelium of other prostatic lobes
      was not markedly different from that of the controls. In conclusion,
      dermatopontin may be involved in the pathogenesis and growth of the prostate
      cancer.

PMID- 16899569
TI  - Deiodinase type 1 activity is expressed in the prostate of pubescent rats and is
      modulated by thyroid hormones, prolactin and sex hormones.
AB  - The aim of this study was to characterize the type of 5'-deiodinase activity in
      the prostate of pubescent rats (7-8 weeks), to establish its distribution in the
      lobes (ventral, dorsolateral, and anterior), and to analyze its modulation by
      prolactin (PRL), testosterone, dihydrotestosterone (DHT), and 17beta-estradiol
      (E(2)). Our results showed that the enzymatic activity was highly susceptible to
      inhibition by 6-n-propyl-2-thiouracil and gold thioglucose, its preferential
      substrate was reverse tri-iodothyronine (rT(3)), it exhibited a low
      dithiothreitol requirement (5 mM), and the apparent K(m) and V(max) values for
      substrate (rT(3)) were approximately 0.25 microM and 9.0 pmol liberated/mg
      protein per hour, respectively. All these characteristics indicate the
      preferential expression of type 1 deiodinase (D1), which was corroborated by
      demonstrating the presence of D1 mRNA in prostate. D1 activity was detected in
      all lobes and was most abundant in the dorsolateral. Although we detected type 2
      deiodinase (D2) mRNA expression, the D2 activity was almost undetectable. D1
      activity was enhanced in animals with hyperthyroidism and hyperprolactinemia, in
      intact animals treated with finasteride (inhibitor of local DHT production), and
      in castrated animals with E(2) replacement. In contrast, activity diminished in
      castrated animals with testosterone replacement. Our results suggest that thyroid
      hormones, PRL, and E(2) exert a positive modulation on D1 activity, while
      testosterone and DHT exhibit an inhibitory effect. D1 activity may be associated
      with prostate maturation and/or function.

PMID- 16899570
TI  - Pregnancy-enhanced Ca2+ responses to ATP in uterine artery endothelial cells is
      due to greater capacitative Ca2+ entry rather than altered receptor coupling.
AB  - Uterine artery endothelial cells (UAEC) derived from pregnant (P-UAEC) and
      nonpregnant (NP-UAEC) ewes retain pregnancy-specific differences in cell
      signaling as well as vasodilator production through passage 4. In particular,
      when P- and NP-UAEC are stimulated with ATP over a 2.5 min recording period, they
      exhibit similar initial transient peaks in the intracellular free Ca(2+)
      concentration ([Ca(2+)](i)), but the P-UAEC show a heightened sustained phase. In
      order to establish whether this was due to an altered subclass of purinergic
      receptor (P2), both the dose dependency of [Ca(2+)](i) responses to ADP and UTP
      and the profile of purinergic receptor expression are determined in NP- and P
      UAEC. Our findings indicate that while several isoforms of P2X and P2Y receptors
      are present, it is P2Y2 that is responsible for the ATP-induced initial transient
      peak in both cell types. We also characterized several key components of the ATP
      induced Ca(2+) signaling cascade, including the inositol 1,4,5-trisphosphate
      receptor and G-proteins, but could not confirm any pregnancy-specific variation
      in the protein expression that correlated with pregnancy-specific differences in
      prolonged Ca(2+) signaling. We thus investigated whether such a difference may be
      inherent to the cell itself rather than specific to the purinergic receptor
      signaling pathway. Using thapsigargin (Tg), we were able to demonstrate that the
      initial Tg-sensitive intracellular pool of Ca(2+)is nearly identical with the
      capacity in both cell types, but the P-UAEC is nonetheless capable of greater
      capacitative Ca(2+) entry (CCE) than NP-UAEC. Furthermore, CCE induced by Tg
      could be dramatically inhibited by 2-aminoethoxydiphenyl borate, suggesting a
      role for store-operated channels in the ATP-induced [Ca(2+)](i) response. We
      conclude that changes at the level of capacitative entry mechanisms rather than
      switching of receptor subtype or coupling to phospholipase C underlies pregnancy
      adaptation of UAEC at the level of Ca(2+)signaling.

PMID- 16899571
TI  - Pregnancy-enhanced store-operated Ca2+ channel function in uterine artery
      endothelial cells is associated with enhanced agonist-specific transient receptor
      potential channel 3-inositol 1,4,5-trisphosphate receptor 2 interaction.
AB  - We have previously shown that endothelial cells (EC) derived from the uterine
      artery (UA) of both pregnant (P-UAEC) and nonpregnant (NP-UAEC) ewes show a
      biphasic intracellular free Ca(2+) ([Ca(2+)](i)) response after ATP stimulation.
      In each case, the initial transient peak, caused by the release of Ca(2+) from
      the intracellular Ca(2+) stores, is mediated by purinergic receptor-Y2 and is
      very similar in both cell types. However, the sustained phase in particular,
      caused by the influx of extracellular Ca(2+), is heightened in the P-UAEC, and
      associates with an increased ability of the cells to demonstrate enhanced
      capacitative Ca(2+) entry (CCE) via store-operated channels (SOCs). Herein we
      demonstrated that the difference in the sustained [Ca(2+)](i) response is
      maintained for at least 30 min. When 2-aminoethoxydiphenyl borate (2APB) (an
      inhibitor of the inosital 1,4,5-trisphosphate receptor (IP3R) and possibly SOC)
      was used in conjunction with ATP, it was capable of completely inhibiting CCE.
      Since 2APB can inhibit SOC in some cell types and 2APB was capable of inhibiting
      CCE in the UAEC model, the role of SOC in CCE was first evaluated using the
      classical inhibitor La(3+). The ATP-induced sustained phase was inhibited by 10
      microM La(3+), implying a role for SOC in the [Ca(2+)](i) response. Since
      canonical transient receptor potential channels (TRPCs) have recently been
      identified as putative SOCs in many cell types, including EC, the expression
      levels of several isoforms were evaluated in UAEC. Expression of TRPC3 and TRPC6
      channels in particular was detected, but no significant difference in expression
      level was found between NP- and P-UAEC. Nonetheless, we were able to show that
      IP3R2 interacts with TRPC3 in UAEC, forming a protein complex, and that this
      interaction is considerably enhanced in an agonist sensitive manner by pregnancy.
      Thus, while IP3R and TRPC isoforms are not altered in their expression by
      pregnancy, enhanced functional interaction of TRPC3 with IP3R2 may underlie
      pregnancy-enhanced CCE in the UAEC model and so explain the prolonged [Ca(2+)](i)
      sustained phase seen in response to ATP.

PMID- 16899572
TI  - The regulatory mechanism by which interleukin-6 stimulates GH-gene expression in
      rat GH3 cells.
AB  - The present study was performed to elucidate the effect of interleukin (IL)-6 on
      the human GH (hGH)-gene expression in GH3 rat pituitary tumor cells using stable
      transfection of the hGH promoter fused to a luciferase reporter gene. Our results
      showed that IL-6 (10(2)-10(4) U/ml) stimulated GH secretion and synthesis, and
      promoted the luciferase expression in stably transfected GH3 cells with the
      maximal action of 1.99 times above the control by 10(4) U/ml IL-6. Among the
      inhibitors of signaling transduction pathways, mitogen-activated protein kinase
      kinase (MAPKK/MEK) inhibitor PD98059 (40 microM) and p38 mitogen-activated
      protein kinase (MAPK) inhibitor SB203580 (5 microM) completely blocked the
      stimulatory effect of IL-6. Western blot analysis demonstrated that IL-6 indeed
      increased the activation of phosphorylated MEK and p38 MAPK in GH3 cells. Neither
      overexpression of Pit-1 nor inhibiting Pit-1 expression affected IL-6 induction
      of hGH-promoter activity. To identify the DNA sequence that mediated the effect
      of IL-6, six deletion constructs of hGH promoter were created. The stimulatory
      effect of IL-6 was abolished following deletion of the -196 to -132 bp fragment.
      In conclusion, our data show that IL-6 promotes GH secretion and synthesis by rat
      pituitary GH3 cells. The stimulatory effect of IL-6 on hGH-gene promoter appears
      to require the activation of MEK and p38 MAPK, and a fragment of promoter
      sequence that spans the -196 to -132 bp of the gene, but may be unrelated to Pit
      1 protein.

PMID- 16899573
TI  - Effect of neonatal hyperthyroidism on GH gene expression reprogramming and
      physiological repercussions in rat adulthood.
AB  - The neonatal period (NP) is a critical phase of the development in which the
      expression pattern of most genes is established. Thyroid hormones (TH) play a key
      role in this process and, alterations in its availability in the NP may lead to
      different patterns of gene expression, which might reflect in the permanent
      expression of several genes in the adulthood. GH gene expression in the pituitary
      is greatly dependent on TH in the early postnatal life; thus, modifications of
      thyroid state in NP might lead to alterations in GH gene expression as well as to
      physiological repercussions in the adult life. This study aimed to investigate
      this possibility by means of the induction of a neonatal hyperthyroidism in rats
      (4 mug of 3,5,3'-triiodo-l-thyronine (T3)/100 g body weight, s.c.) for 5, 15 or
      30 days, and further evaluation of GH gene expression, as well as its
      physiological consequences in adult rats subjected to a transient hyperthyroidism
      in the first 30 days of life. GH mRNA level was shown to be increased in T3
      treated rats for 5 days; when the treatment was extended to 15 or 30 days, the GH
      mRNA levels were similar to the control group. Moreover, rats treated with T3 for
      30 days and killed when 90 days old, i.e., 60 days at the end of the T3
      treatment, showed decreased GH mRNA content, body weight, bone mineral density,
      and lean body mass. IN CONCLUSION: (1) T3 effects on GH gene expression depend on
      the period of life in which the hyperthyroidism is set and on the length of T3
      treatment in the NP and (2) transient neonatal hyperthyroidism leads to a lower
      GH mRNA expression in adult life accompanied by physiological repercussions
      indicative of GH deficiency.

PMID- 16899574
TI  - Clodronate alleviates cachexia and prolongs survival in nude mice xenografted
      with an anaplastic thyroid carcinoma cell line.
AB  - Cancer cachexia is one of the most common manifestations of advanced malignant
      disease and is frequently associated with decreased survival. Previously, we
      reported the establishment of a new anaplastic thyroid carcinoma cell line,
      Thena, and its mouse xenograft, Thena-Nu, which induced cachexia in athymic nude
      mice. Subsequent studies showed that the addition of clodronate to Thena-Nu
      cultures reduced cell proliferation as well as cytokine production in a dose- and
      time-dependent manner. Weekly administration of clodronate induced tumor
      cytostasis, attenuation of cachexia, as well as prolongation of survival in Thena
      Nu-bearing mice. Reduced serum interleukin 6, tumor necrosis factor-alpha, and
      granulocyte colony stimulating factor levels were detected, whereas, serum
      leukemia inhibitory factor levels were not reduced. Liver necrosis, observed in
      tumor-bearing mice, was also improved following clodronate treatment.
      Discontinuation of clodronate treatment, however, resulted in progressive tumor
      growth and weight loss. Our results demonstrated that clodronate could exert
      therapeutic efficacy on amelioration of cancer cachexia in the hosts.
      Nevertheless, this study also points out that a longer period of treatment is
      required to maintain these effects.

PMID- 16899575
TI  - Sexual dimorphism in insulin sensitivity and susceptibility to develop diabetes
      in rats.
AB  - The goal of this study was to evaluate gender-related differences of some
      metabolic determinants of insulin sensitivity and of susceptibility to the
      effects of diabetes. Changes in body weight, blood glucose, and serum insulin
      concentrations were compared between female and male Wistar rats in prepubertal,
      pubertal, and adult stages of life. A diabetic model was induced by
      streptozotocin (STZ) under nicotinamide protection in both sexes and metabolic
      patterns were evaluated during the next 4 weeks. Finally, the pancreases were
      processed for morphometric analysis. In the three age groups, at similar blood
      glucose levels, higher fasting serum insulin levels were found in female as
      compared with age matched male rats. After STZ treatment, female rats show lower
      insulin and higher glucose levels, and a worse survival rate as compared with
      male rats. The more severe disease phenotype observed in female animals is
      associated with a more dramatic perturbation of pancreatic islet morphology.
      Significant differences exist in insulin sensitivity between sexes, females being
      less sensitive to insulin than males at all age groups and more susceptible to
      the rapid development of a more severe form of diabetes than males.

PMID- 16899576
TI  - Downregulation of the constitutively expressed Hsc70 in diabetic myocardium is
      mediated by insulin deficiency.
AB  - The 70 kDa heat shock protein family plays important cardiac protective roles
      against myocardial injuries. Reduced myocardial protection is a common feature of
      diabetic myocardium. This study was carried out to define the changes in the 70
      kDa heat shock protein family in the myocardium in the of streptozotocin-diabetes
      rats, and to explore the mechanisms through which diabetes alters the abundance
      of Hsp70/Hsc70 in cardiac muscle. In the diabetic myocardium, the abundance of
      Hsc70 was significantly reduced. The abundance of Hsp70 was low in cardiac muscle
      and was not induced in the diabetic myocardium. Unlike Hsp60, Hsp70 and Hsc70 did
      not augment insulin-like growth factor-I receptor signaling in cardiac muscle
      cells. In cultured cardiomyocytes, insulin directly increased the abundance of
      Hsc70, whereas insulin could not modulate Hsp70. Treating diabetic rats with
      insulin restored myocardial Hsc70 level, but phlorizin treatment failed to
      restore myocardial Hsc70. These in vivo and in vitro studies showed that
      downregulation of Hsc70 in diabetic myocardium was secondary to insulin
      deficiency. Thus, insulin played a major role in maintaining adequate expression
      of Hsc70 in cardiac muscle.

PMID- 16899577
TI  - Enhancement of muscle glucose uptake by the vasopeptidase inhibitor, omapatrilat,
      is independent of insulin signaling and the AMP kinase pathway.
AB  - Omapatrilat (OMA), a vasopeptidase inhibitor (VPI), presently being tested in
      clinical trials for its antihypertensive properties, inhibits both angiotensin
      converting enzyme and neutral endopeptidase, and raises tissue bradykinin levels.
      Recent studies from our laboratory and those of others have demonstrated that
      VPIs enhance muscle glucose uptake in animal models, and this effect is mediated
      by the bradykinin-nitric oxide pathway. The mechanism of the effect of OMA on
      muscle glucose uptake, however, is presently unknown. To investigate the effect
      of OMA on insulin signaling, soleus muscle was isolated 2 or 5 min after an i.v.
      bolus of insulin or saline from male Zucker fatty rats (8-10 weeks of age),
      following a 5-day treatment period of oral OMA (15 mg/kg per day) or drug vehicle
      (placebo). OMA resulted in significantly lower systolic blood pressure compared
      with the placebo-treated group (84.4+/- 7.52 mmHg in OMA vs 112+/-2.18 mmHg in
      controls, P<0.01). Immunoprecipitation and Western blot analysis of insulin
      receptor substrate 1 (IRS-1) revealed no changes in protein mass with OMA
      treatment. OMA did not enhance basal or insulin-stimulated IRS-1 tyrosine
      phosphorylation or its subsequent association with the p85 regulatory subunit of
      phosphatidylinositol 3-kinase. Under basal and insulin-stimulated conditions, OMA
      treatment did not alter the protein mass or the phosphorylation of Akt/protein
      kinase B, p42/44 extracellular signal-regulated kinase or adenosine monophosphate
      activated protein kinase, or GLUT4 protein expression. We conclude that the
      ability of OMA to enhance whole body and specifically muscle glucose uptake in
      Zucker fatty rats is not mediated by enhancing insulin or AMPK signaling. Future
      studies should examine whether hemodynamic effects of the drug, independent of
      insulin signaling, enhance glucose uptake in insulin-resistant skeletal muscle.

PMID- 16899578
TI  - Up-regulation of the phosphatidylinositol 3-kinase/protein kinase B pathway in
      the ovary of rats by chronic treatment with hCG and insulin.
AB  - Polycystic ovary syndrome (PCOS) manifests as chronic anovulation, ovarian
      hyperandrogenism, and follicular cysts, which are amplified by insulin as well as
      the inability of the hormone to stimulate glucose uptake in classic target
      tissues such as muscle and fat. In the present study, we evaluated the regulation
      of the insulin-signaling pathways by using immunoprecipitation and immunoblotting
      in whole extracts of ovaries from non-pregnant human chorionic gonadotropin (hCG)
      treated rats, hyperinsulinemic-induced rats and hyperinsulinemic-induced rats,
      treated with hCG for 22 consecutive days. There were increased associations of
      insulin receptor substrate (IRS)-1 and IRS-2 with phosphatidylinositol (PI) 3
      kinase, followed by enhanced protein kinase B (Akt) serine and threonine
      phosphorylation, in the ovaries of rats that were treated with hCG, either alone
      or with insulin. In contrast, the skeletal muscle demonstrated a reduced IRS-1/PI
      3-kinase/Akt pathway in hyperinsulinemic-induced rats. These intracellular
      modifications were accompanied by follicular cysts, detected by optical
      microscopy, and increased androstenedione serum levels. In summary, our data show
      that chronic treatment with hCG or hCG plus insulin can induce changes in ovaries
      that simulate PCOS. In these situations, an increase in the insulin-induced
      IRS/PI 3-kinase/Akt pathway occurs in the ovary, suggesting that the activation
      of this pathway may have a role in the development of PCOS.

PMID- 16899579
TI  - Cell specificity of the cytoplasmic Ca2+ response to tolbutamide is impaired in
      beta-cells from hyperglycemic mice.
AB  - We recently reported that the timing and magnitude of the nutrient-induced Ca(2+)
      response are specific and reproducible for each isolated beta-cell. We have now
      used tolbutamide and arginine to test if the cell specificity exists also for the
      response to non-nutrient stimulation of beta-cells and if so, whether it is
      disturbed in beta-cells from hyperglycemic ob/ob and db/db mice. Zn(2+) outflow
      measurements were used to study the correlation between Ca(2+) response and
      insulin secretion in individual beta-cells. Tolbutamide and arginine induced cell
      specific Ca(2+) responses in lean mouse beta-cells both with regard to lag times
      for [Ca(2+)](i) rise and peak [Ca(2+)](i) heights. beta-Cells within intact
      islets also showed cell-specific timing of their Ca(2+) responses to tolbutamide.
      However, in tolbutamide- and arginine-stimulated single beta-cells from ob/ob and
      db/db mice only the magnitude of Ca(2+) response was cell-specific, not the
      timing. The lag time of tolbutamide-induced insulin secretion was cell-specific
      in lean mouse beta-cells but not in ob/ob mouse cells. Therefore, cell
      specificity seems to be a robust mechanism, and probably important for an
      adequate beta-cell function. The loss of temporal cell specificity for the
      response to tolbutamide in single beta-cells from hyperglycemic mice may be a
      sign of K(ATP)- or voltage-dependent calcium channel dysfunction.

PMID- 16899580
TI  - Exercise and dexamethasone oppositely modulate beta-cell function and survival
      via independent pathways in 90% pancreatectomized rats.
AB  - Long-term dexamethasone (DEX) treatment is well known for its ability to increase
      insulin resistance in liver and adipose tissues leading to hyperinsulinemia. On
      the other hand, exercise enhances peripheral insulin sensitivity. However, it is
      not clear whether DEX and/or exercise affect beta-cell mass and function in
      diabetic rats, and whether their effects can be associated with the modulation of
      the insulin/IGF-I signaling cascade in pancreatic beta-cells. After an 8-week
      study, whole body glucose disposal rates in 90% pancreatectomized (Px) and sham
      operated male rats decreased with a high dose treatment of DEX (0.1mg DEX/kg body
      weight/day)(HDEX) treatment, while disposal rates increased with exercise. First
      phase insulin secretion was decreased and delayed by DEX via the impairment of
      the glucose-sensing mechanism in beta-cells, while exercise reversed the
      impairment of first-phase insulin secretion caused by DEX, suggesting ameliorated
      beta-cell functions. However, exercise and DEX did not alter second-phase insulin
      secretion except for the fact that HDEX decreased insulin secretion at 120 min
      during hyperglycemic clamp in Px rats. Unlike beta-cell functions, DEX and
      exercise exhibited increased pancreatic beta-cell mass in two different pathways.
      Only exercise, through increased proliferation and decreased apoptosis, increased
      beta-cell mass via hyperplasia, which resulted from an enhanced insulin/IGF-I
      signaling cascade by insulin receptor substrate 2 induction. By contrast, DEX
      expanded beta-cell mass via hypertrophy and neogenesis from precursor cells,
      rather than increasing proliferation and decreasing apoptosis. In conclusion, the
      improvement of beta-cell function and survival via the activation of an
      insulin/IGF-I signaling cascade due to exercise has a crucial role in preventing
      the development and progression of type 2 diabetes.

PMID- 16899581
TI  - Characterisation of the prereceptor regulation of glucocorticoids in the anterior
      segment of the rabbit eye.
AB  - The prereceptor regulation of glucocorticoids (GCs) by 11beta-hydroxysteroid
      dehydrogenase type-1 (11beta-HSD1), a bidirectional isozyme that interconverts
      active (cortisol) and inactive (cortisone) GCs, is an established determinant of
      GC function in tissues such as liver, adipose and bone. Although the therapeutic
      use of GCs is abundant in ophthalmic practice, where GC interactions with nuclear
      receptors modulate gene transcription, the prereceptor regulation of endogenous
      cortisol is not well described in ocular tissues. Recent descriptive studies have
      localised 11beta-HSD1 to the human corneal epithelium and non-pigmented
      epithelium (NPE) of the ciliary body, indicating a link to corneal epithelial
      physiology and aqueous humour production. In this study, we characterise the
      functional aspects of the autocrine regulation of GCs in the anterior segment of
      the rabbit eye. Using our in-house generated primary antibody to human 11beta
      HSD1, immunohistochemical analyses were performed on paraffin-embedded sections
      of whole New Zealand white albino rabbits, (NZWAR) eyes. As in human studies,
      11beta-HSD1 was localised to the corneal epithelium and the NPE. No staining was
      seen in the albino 'pigmented' ciliary epithelium. Specific enzyme assays for oxo
      reductase (cortisone-->cortisol) and dehydrogenase (cortisol-->cortisone)
      activity indicated predominant 11beta-HSD1 oxo-reductase activity from both the
      intact ciliary body tissue (n=12, median 2.1 pmol/mg per h and range 1.25-2.8
      pmol/mg per h; P=0.006) and primary cultures of corneal epithelial cells (n=12,
      median 3.0 pmol/mg per h and range 1.0-7.4 pmol/mg per h, P=0.008) compared with
      dehydrogenase activity (median 1.0 pmol/mg per h and range 0.5-2.0 pmol/mg per h;
      median 0.5 pmol/mg per h and range 0.25-1.9 pmol/mg per h respectively). These
      findings were supported by expression of 11beta-HSD1 protein as visualised by
      Western blotting of ciliary body tissue and immunocytochemistry of corneal
      epithelial cells. Reduction of corneal epithelial cell proliferation was seen
      after primary cultures were co-incubated with cortisol and cortisone. 11beta-HSD1
      activity was not demonstrated in naive conjunctival fibroblasts or corneal
      stromal keratocytes. Our results indicate that the distribution of 11beta-HSD1 in
      the rabbit resembles that of the human eye and activates cortisone to cortisol in
      both corneal and uveal tissues. The NZWAR provides a suitable in vivo model for
      the further evaluation of 11beta-HSD1 activity in the eye, especially its role in
      corneal epithelial and ciliary body physiology.

PMID- 16899582
TI  - Endogenous glucocorticoids cause thymus atrophy but are protective during acute
      Trypanosoma cruzi infection.
AB  - The cytokine-mediated stimulation of the hypothalamus-pituitary-adrenal (HPA)
      axis is relevant for survival during bacterial endotoxemia and certain viral
      infections. However, only limited information is available regarding the effects
      of endogenous glucocorticoids on parasite diseases. We have studied this issue
      using, as a model, C57Bl/6 and Balb/c mice infected with Trypanosoma cruzi, the
      causal agent of Chagas' disease. These two mouse strains differ in the
      susceptibility to infection with the parasite. An intense stimulation of the HPA
      axis was observed 3 weeks after infection in both strains, but glucocorticoid
      levels were already increased two- to threefold in the less susceptible Balb/c
      strain during the first week. Blockade of glucocorticoid receptors with the
      glucocorticoid antagonist RU486, starting on day 10 after infection, partially
      reversed the thymic atrophy and decreased the number of CD4(+)CD8(+) thymocytes
      without affecting parasitemia and the number of inflammatory foci in the heart.
      However, tumor necrosis factor-alpha blood levels were increased in infected mice
      of both strains treated with RU486. Furthermore, the blockade of glucocorticoid
      receptors accelerated death in C57Bl/6J mice and increased lethality to 100% in
      Balb/c mice. The results obtained represent the first evidence that an endocrine
      host response that is coupled to the immune process can strongly affect the
      course of a parasite infection.

PMID- 16899583
TI  - Adrenomedullin increases the expression of calcitonin-like receptor and receptor
      activity modifying protein 2 mRNA in human microvascular endothelial cells.
AB  - Adrenomedullin (AM) is a multifunctional peptide hormone, which plays a
      significant role in vasodilation and angiogenesis, implicating it in hypertension
      as well as in carcinogenesis. AM exerts its effects via the calcitonin receptor
      like receptor (CRLR, now known as CL) complexed with either receptor activity
      modifying protein (RAMP) 2 or 3. We have investigated the effect of AM on
      immortalized human microvascular endothelial cells 1, since endothelial cells are
      a major source as well as a target of AM actions in vivo. Cells treated with AM
      showed elevated cAMP in a time (5-45 min)-dependent and dose (10(-6)-10(-14) M)
      dependent manner. Pre-treatment with the AM receptor antagonist AM(22-52)
      partially suppressed the AM-induced increase in cAMP levels. An increase in
      extracellular signal-regulated kinase 1/2 phosphorylation was observed after 5
      min of treatment with 10(-8) M AM. This phosphorylation was specific, since we
      were able to block the AM-induced effect with 1 microM U0126, a specific mitogen
      activated protein/extracellular signal-regulated kinase kinase inhibitor. Using
      real-time PCR, we were able to show for the first time that AM upregulates
      peptide and mRNA expression of vascular endothelial growth factor (VEGF).
      However, AM treatment of cells did not result in increased cell proliferation.
      Instead, we observed that AM and VEGF induced cell migration, which could be
      inhibited by the AM(22-52) and anti-VEGF antibody respectively. AM also
      significantly elevated mRNA levels of CL (after 2 and 24 h treatment) and RAMP2
      (after 1 and 24 h treatment). The upregulation of the AM receptor at two time
      points reflects possibly different cellular responses to short- and long-term
      exposure to AM.

PMID- 16899584
TI  - Peripheral administration of the N-terminal pro-opiomelanocortin fragment 1-28 to
      Pomc-/- mice reduces food intake and weight but does not affect adrenal growth or
      corticosterone production.
AB  - Pro-opiomelanocortin (POMC) is a polypeptide precursor that undergoes extensive
      processing to yield a range of peptides with biologically diverse functions. POMC
      derived ACTH is vital for normal adrenal function and the melanocortin alpha-MSH
      plays a key role in appetite control and energy homeostasis. However, the roles
      of peptide fragments derived from the highly conserved N-terminal region of POMC
      are less well characterized. We have used mice with a null mutation in the Pomc
      gene (Pomc(-/-)) to determine the in vivo effects of synthetic N-terminal 1-28
      POMC, which has been shown previously to possess adrenal mitogenic activity. 1-28
      POMC (20 mug) given s.c. for 10 days had no effect on the adrenal cortex of Pomc(
      /-) mice, with resultant cortical morphology and plasma corticosterone levels
      being indistinguishable from sham treatment. Concurrent administration of 1-28
      POMC and 1-24 ACTH (30 mug/day) resulted in changes identical to 1-24 ACTH
      treatment alone, which consisted of upregulation of steroidogenic enzymes,
      elevation of corticosterone levels, hypertrophy of the zona fasciculate, and
      regression of the X-zone. However, treatment of corticosterone-depleted Pomc(-/-)
      mice with 1-28 POMC reduced cumulative food intake and total body weight. These
      anorexigenic effects were ameliorated when the peptide was administered to Pomc(
      /-) mice with circulating corticosterone restored either to a low physiological
      level by corticosterone-supplemented drinking water (CORT) or to a
      supraphysiological level by concurrent 1-24 ACTH administration. Further, i.c.v.
      administration of 1-28 POMC to CORT-treated Pomc(-/-) mice had no effect on food
      intake or body weight. In wild-type mice, the effects of 1-28 POMC upon food
      intake and body weight were identical to sham treatment, but 1-28 POMC was able
      to ameliorate the hyperphagia induced by concurrent 1-24 ACTH treatment. In a
      mouse model which lacks all endogenous POMC peptides, s.c. treatment with
      synthetic 1-28 POMC alone can reduce food intake and body weight, but has no
      impact upon adrenal growth or steroidogenesis.

PMID- 16899586
TI  - Differential effects of leptin and refeeding on the fasting-induced decrease of
      pituitary type 2 deiodinase and thyroid hormone receptor beta2 mRNA expression in
      mice.
AB  - Profound changes in thyroid hormone metabolism occur in the central part of the
      hypothalamus-pituitary-thyroid (HPT) axis during fasting. Hypothalamic changes
      are partly reversed by leptin administration, which decreases during fasting. It
      is unknown to what extent leptin affects the HPT axis at the level of the
      pituitary. We, therefore, studied fasting-induced alterations in pituitary
      thyroid hormone metabolism, as well as effects of leptin administration on these
      changes. Because refeeding rapidly increased serum leptin, the same parameters
      were studied after fasting followed by refeeding. Fasting for 24 h decreased
      serum T(3) and T(4) and pituitary TSHbeta, type 2deiodinase (D2), and thyroid
      hormone receptor beta2 (TRbeta2) mRNA expression. The decrease in D2 and TRbeta2
      mRNA expression was prevented when 20 mug leptin was administered twice during
      fasting. By contrast, the decrease in TSHbeta mRNA expression was unaffected. A
      single dose of leptin given after 24 h fasting did not affect decreased TSHbeta,
      D2, and TRbeta2 mRNA expression, while 4 h refeeding resulted in pituitary D2 and
      TRbeta2 mRNA expression as observed in control mice. Serum leptin, T(3), and T(4)
      after refeeding were similar compared with leptin administration. We conclude
      that fasting decreases pituitary TSHbeta, D2, and TRbeta2 mRNA expression, which
      (with the exception of TSHbeta) can be prevented by leptin administration during
      fasting. Following 24 h fasting, 4 h refeeding completely restores pituitary D2
      and TRbeta2 mRNA expression, while a single leptin dose is ineffective. This
      indicates that other postingestion signals may be necessary to modulate rapidly
      the fasting-induced decrease in pituitary D2 and TRbeta2 mRNA expression.

PMID- 16899585
TI  - The melanocortin circuit in obese and lean strains of chicks.
AB  - Agonists of membranal melanocortin 3 and 4 receptors (MC3/4Rs) are known to take
      part in the complex control mechanism of energy balance. In this study, we
      compared the physiological response to an exogenous MC3/4R agonist and the
      hypothalamic expression of proopic melanocortin (POMC) gene, encoding few MC3/4R
      ligands, between broiler and layer chicken strains. These strains, representing
      the two most prominent commercial strains of chickens grown for meat (broilers)
      and egg production (layers), differ in their food intake, fat accumulation, and
      reproductive performance and, therefore, form a good model of obese and lean
      phenotypes, respectively. A single i.v. injection of the synthetic peptide
      melanotan-II (MT-II; 1 mg/kg body weight) into the wing vein of feed-restricted
      birds led to attenuation of food intake upon exposure to feeding ad libitum in
      both broiler and layer chickens. A study of the POMC mRNA encoding the two
      prominent natural MC3/4R agonists, alpha-MSH and ACTH, also revealed a general
      similarity between the strains. Under feeding conditions ad libitum, POMC mRNA
      levels were highly similar in chicks of both strains and this level was
      significantly reduced upon feed restriction. However, POMC mRNA down-regulation
      upon feed restriction was more pronounced in layers than in broilers. These
      results suggest: (i) a role for MC3/4R agonists in the control of appetite; (ii)
      that the physiological differences between broilers and layers are not related to
      unresponsiveness of broiler chickens to the satiety signal of MC3/4R ligands.
      Therefore, these findings suggest that artificial activation of this circuit in
      broiler chicks could help to accommodate with their agricultural shortcomings of
      overeating, fattening, and impaired reproduction.

PMID- 16899587
TI  - Negative energy balance and leptin regulate neuromedin-U expression in the rat
      pars tuberalis.
AB  - Central neuromedin U (NMU) functions in energy balance, the hypothalamic
      pituitary-adrenal axis, LH release and circadian rhythmicity. In rats, high
      levels of NMU occur in the hypothalamic suprachiasmatic nuclei and the pars
      tuberalis of the pituitary. NMU expression in the pars tuberalis appears to be
      downregulated in the Zucker fatty (fa/fa) rat, lacking functional leptin
      receptors. In contrast, in the dorsomedial (DMH) nuclei of the mouse, NMU
      expression is higher in the ob/ob mouse, lacking leptin, and is upregulated by
      fasting. However, leptin appears not to change NMU gene expression in either the
      mouse DMH or the rat pars tuberalis. Thus, the present study aims to better
      identify factors influencing central NMU expression in the rat pars tuberalis.
      Sprague-Dawley rats were fasted and/or challenged with intracerebroventricular
      leptin or ghrelin and gene expression was measured using real-time reverse
      transcriptase-PCR and quantitative in situ hybridisation with riboprobes specific
      for NMU and NMU receptor (NMU-R2). NMU expression in the rat pars tuberalis was
      elevated by fasting. Ghrelin administration had no effect on the level of NMU
      expression, but leptin was found to diminish the expression in a concentration-
      and time-dependent manner. NMU-R2 expression was unchanged in any of the groups
      measured. These results suggest that NMU expression in rat pars tuberalis is
      upregulated in states of negative energy balance, and this may be mediated
      indirectly by changes in leptin levels. These results demonstrate a link between
      energy balance and NMU expression in the pars tuberalis of the pituitary.

PMID- 16899588
TI  - Antisense to cyclin D1 inhibits VEGF-stimulated growth of vascular endothelial
      cells: implication of tumor vascularization.

PMID- 16899589
TI  - Targeting the double-strand DNA break repair pathway as a therapeutic strategy.
AB  - DNA repair pathways are crucial for the maintenance of genome integrity. The
      pathway that repairs DNA double-strand breaks (DSB) has components involved in
      both signaling and repairing DNA damage. Impairing DSB repair using specific
      inhibitors of signaling or repair might, in principle, sensitize tumor cells to
      particular DNA-damaging agents. Moreover, the existence of specific defects in
      DNA repair pathways in tumors provides the rationale for the use of "synthetic
      lethal" approaches targeting this cellular "Achilles' heel." Here, we discuss the
      mechanisms involved in DSB repair and detail potential therapeutic approaches
      based on targeting this pathway.

PMID- 16899590
TI  - Statistical analysis of DNA microarray data in cancer research.
AB  - Microarray techniques have been widely used to monitor gene expression in many
      areas of biomedical research. They have been widely used for tumor diagnosis and
      classification, prediction of prognoses and treatment, and understanding of
      molecular mechanisms, biochemical pathways, and gene networks. Statistical
      methods are vital for these scientific endeavors. This article reviews recent
      developments of statistical methods for analyzing data from microarray
      experiments. Emphasis has been given to normalization of expression from multiple
      arrays, selecting significantly differentially expressed genes, tumor
      classifications, and gene expression pathways and networks.

PMID- 16899591
TI  - The chemokine CCL5 as a potential prognostic factor predicting disease
      progression in stage II breast cancer patients.
AB  - PURPOSE: The aim of this study was to determine the prognostic value of the
      chemokine CCL5, considered as a promalignancy factor in breast cancer, in
      predicting breast cancer progression and to evaluate its ability to strengthen
      the prognostic significance of other biomarkers. EXPERIMENTAL DESIGN: The
      expression of CCL5, alone and in conjunction with estrogen receptor (ER)-alpha,
      ER-beta, progesterone receptor (PR), and HER-2/neu (ErbB2), was determined in
      breast tumor cells by immunohistochemistry. The study included 142 breast cancer
      patients, including individuals in whom disease has progressed. RESULTS: Using
      Cox proportional hazard models, univariate analysis suggested that, in stage I
      breast cancer patients, CCL5 was not a significant predictor of disease
      progression. In contrast, in stage II patients, the expression of CCL5 (CCL5(+)),
      the absence of ER-alpha (ER-alpha(-)), and the lack of PR expression (PR(-))
      increased significantly the risk for disease progression (P = 0.0045, 0.0041, and
      0.0107, respectively). The prognostic strength of CCL5, as well as of ER-alpha(
      ), improved by combining them together (CCL5(+)/ER-alpha(-): P = 0.0001), being
      highly evident in the stage IIA subgroup [CCL5(+)/ER-alpha(-) (P = 0.0003); ER
      alpha(-) (P = 0.0315)]. In the stage II group as a whole, the combinations of
      CCL5(-)/ER-alpha(+) and CCL5(-)/PR(+) were highly correlated with an improved
      prognosis. Multivariate analysis indicated that, in stage II patients, ER-alpha
      and CCL5 were independent predictors of disease progression. CONCLUSIONS: CCL5
      could be considered as a biomarker for disease progression in stage II breast
      cancer patients, with the CCL5(+)/ER-alpha(-) combination providing improved
      prediction of disease progression, primarily in the stage IIA subgroup.

PMID- 16899592
TI  - Oxaliplatin and axonal Na+ channel function in vivo.
AB  - PURPOSE: The aim of the study was to investigate the pathophysiology of
      oxaliplatin-induced neurotoxicity using clinical nerve excitability techniques
      that provide information about axonal ion channel function. EXPERIMENTAL DESIGN:
      Excitability studies were combined with standard nerve conduction studies and
      clinical assessment in 22 patients undergoing treatment with oxaliplatin.
      RESULTS: Excitability studies recorded before and immediately after oxaliplatin
      infusion for 89 treatment cycles revealed significant increases in refractoriness
      and relative refractory period postinfusion in all patients, consistent with an
      effect of oxaliplatin on axonal Na(+) channels. However, those patients that
      developed chronic neuropathy had significantly greater changes. Following
      cessation of oxaliplatin treatment, 41% of patients had persistent symptoms and
      nerve conduction abnormalities consistent with the development of chronic
      neuropathy. CONCLUSION: The present study provides evidence that oxaliplatin
      induced neurotoxicity is mediated through an effect on axonal Na(+) channels.
      Clinical nerve excitability techniques may prove beneficial in monitoring for
      early signs of neurotoxicity and in the assessment of future prophylactic
      therapies.

PMID- 16899593
TI  - RhoC GTPase expression as a potential marker of lymph node metastasis in squamous
      cell carcinomas of the head and neck.
AB  - PURPOSE: Survival rates for squamous cell carcinoma of the head and neck (SCCHN)
      have remained unchanged for several decades due to local tumor recurrences as
      well as regional and distant metastases. Recent evidence has shown that RhoC
      GTPase is overexpressed in stages III and IV regionally metastatic SCCHN compared
      with stages I and II localized disease. This study evaluated the expression of
      RhoC in head and neck carcinoma and investigated the prognostic use of this
      marker on a large cohort of previously untreated patients with SCCHN.
      EXPERIMENTAL DESIGN: Standard Western blot techniques were used to evaluate RhoC
      protein expression in nine established head and neck cancer cell lines and in
      normal oral epithelium. In vivo expression of RhoC in metastatic and
      nonmetastatic SCCHN was investigated using immunohistochemical analysis on a
      tissue microarray composed of 113 independent tumor samples. RhoC expression was
      analyzed as it related to clinical and pathologic variables of interest. RESULTS:
      Levels of RhoC protein were increased in the SCCHN cell lines compared with
      normal oral epithelium. The in vivo expression of RhoC correlated with advanced
      clinical stage and lymph node metastases for the entire patient cohort as well as
      in small primary tumors (T(1) and T(2)). CONCLUSIONS: This study is the first to
      examine the expression of RhoC GTPase protein in SCCHN and normal squamous
      epithelium. It is clear from the results that RhoC is a specific marker of lymph
      node metastases in patients with this challenging form of carcinoma. RhoC levels
      seem to identify a subset of patients with early tumor stage primary tumors and
      high metastatic potential that might benefit from more aggressive therapy.
      Through continued investigation, blockade of RhoC activity may be a potential
      target in the development of novel strategies for treating metastases of head and
      neck cancer.

PMID- 16899594
TI  - Induction of interleukin-6 by hepatitis C virus core protein in hepatitis C
      associated mixed cryoglobulinemia and B-cell non-Hodgkin's lymphoma.
AB  - PURPOSE: Chronic hepatitis C carries the risk to develop mixed cryoglobulinemia
      (MC) and B-cell non-Hodgkin's lymphoma (B-NHL), possibly because viral antigens
      stimulate the host's inflammatory response via extracellular pattern recognition
      receptors (PRR). To clarify this issue, we studied whether recognition of
      hepatitis C virus (HCV) proteins by PRR is involved in the pathogenesis of HCV
      associated MC or B-NHL. EXPERIMENTAL DESIGN: Peripheral blood mononuclear cells
      of patients with HCV-associated B-NHL (n = 12), MC (n = 14), uncomplicated
      hepatitis C (n = 12), and healthy volunteers (n = 12) were incubated with the
      recombinant HCV proteins E2, core, and NS3 to study induction of cytokine
      production, stimulation of B-cell proliferation, and immunoglobulin secretion. In
      addition, serum levels of interleukin-6 (IL-6) were measured by ELISA. RESULTS:
      HCV core was the only studied protein, which induced production of IL-6 and IL-8
      in CD14(+) cells. IL-6 induction was mediated via Toll-like receptor 2 (TLR2) and
      lead to increased B-cell proliferation in vitro. TLR2 expression on monocytes and
      IL-6 serum concentrations were increased in all groups of HCV-infected patients
      compared with healthy controls and were highest in MC (P < 0.05). CONCLUSIONS:
      Increased secretion of IL-6 via stimulation of TLR2 by HCV core protein may play
      a role in the pathogenesis of hepatitis C-associated MC and B-NHL.

PMID- 16899595
TI  - Cutaneous melanoma subtypes show different BRAF and NRAS mutation frequencies.
AB  - PURPOSE: BRAF mutations are present in two thirds of cutaneous melanomas and many
      of the rest have NRAS mutations. However, cutaneous melanoma is a heterogeneous
      disease with many clinicopathologic subtypes. Of these, the majority fits into
      four categories: superficial spreading, nodular, lentigo maligna, and acral
      lentiginous melanoma (ALM). Thus far, there is very limited data combining BRAF
      and NRAS mutation analysis to explore differences between cutaneous melanoma
      subtypes. The aim of this study was to address this issue. EXPERIMENTAL DESIGN:
      The frequency of BRAF and NRAS hotspot mutations, in exons 15 and 2,
      respectively, was assessed in 59 cutaneous melanomas comprising superficial
      spreading, nodular, lentigo maligna, and ALM using single-strand conformational
      polymorphism and RFLP-PCR analysis. RESULTS: Only 2 of 21 (9.5%) ALM showed BRAF
      exon 15 mutation compared with 9 of 14 (64.3%) superficial spreading malignant
      melanomas, 4 of 11 (36.4%) nodular melanomas, and 7 of 13 (53.4%) lentigo maligna
      melanomas (P < 0.01). However, our key finding is that the combined analysis of
      BRAF exon 15 and NRAS exon 2 showed that there were no significant differences in
      the overall mutation frequency between subtypes. In particular, 9 of 19 (47.4%)
      ALM without BRAF exon 15 mutation had an NRAS exon 2 mutation. CONCLUSIONS: We
      show that the overall BRAF/NRAS frequency in mutation hotspots is not
      significantly different among cutaneous melanoma subtypes. These data show that
      mitogen-activated protein kinase pathway activation may be important in all major
      subtypes of cutaneous melanoma, although the mechanism by which this is achieved
      varies.

PMID- 16899596
TI  - Hypoxia-inducible factor-1alpha and hypoxia-inducible factor-2alpha are expressed
      in kaposi sarcoma and modulated by insulin-like growth factor-I.
AB  - PURPOSE: Neoangiogenesis is essential for tumor development. Hypoxia-inducible
      factor (HIF), a transcriptional factor composed of two subunits (alpha and beta),
      plays a key role in this process, activating proangiogenic factors such as
      vascular endothelial growth factor (VEGF). The HIF alpha subunits are critically
      regulated by oxygen and are also modulated by growth factors. Kaposi sarcoma (KS)
      is a highly vascular tumor that releases large amounts of VEGF and for which we
      have recently described an essential role for the insulin-like growth factor
      (IGF) system. We therefore investigated the expression of HIF alpha subunits in
      biopsies from KS tumors and their modulation by IGF-I in KSIMM, a KS cell line.
      RESULTS: Both HIF-1alpha and HIF-2alpha were expressed in KS biopsies in all
      tumoral stages. HIF-1alpha immunopositivity increased through the tumor
      development with highest expression in the late nodular stages. In KSIMM cells,
      IGF-I induced accumulation of both HIF alpha subunits. The induction suggests a
      translation mechanism as documented by cycloheximide chase experiment coupled
      with constant RNA levels as evaluated by quantitative real-time PCR. IGF-I
      induced HIF alpha accumulation was followed by an increase in HIF function as
      assessed both by reporter gene assay and by induction of endogenous target gene
      expression (VEGF-A). Specific blockade of IGF-I receptor with alphaIR3 antibody
      or with picropodophyllin, a specific IGF-IR tyrosine kinase inhibitor, diminishes
      the basal and IGF-I-dependent induction of both HIF alpha congeners. CONCLUSION:
      These novel findings show the coupling between the IGF and HIF signaling in KS
      and suggest a coordinated contribution by these pathways to the characteristic
      vascular phenotype of this tumor.

PMID- 16899597
TI  - Accumulation of promoter methylation suggests epigenetic progression in squamous
      cell carcinoma of the esophagus.
AB  - PURPOSE: Squamous esophageal cancer is common in non-Western countries and has a
      well-defined progression of preinvasive dysplasia leading to invasive squamous
      cell carcinoma. We examined the changes in promoter region methylation occurring
      during neoplastic progression. EXPERIMENTAL DESIGN: The frequency of epigenetic
      changes in the promoter region of 14 genes epigenetically silenced in other
      cancers was determined and examined the most frequent changes in dysplastic
      lesions using methylation-specific PCR. Invasive squamous carcinomas, low to high
      grade dysplasia, and normal esophagus were then examined for methylation changes
      in the promoter region of each of the eight most commonly methylated genes.
      RESULTS: Methylation was most frequent for CDKN2A/p16INK4a (52%) but was also
      common for O(6)-methylguanine-DNA methyltransferase, E-cadherin (CDH1), and
      retinoic acid receptor beta2. Methylation at individual genes increased in
      frequency from normal to invasive cancer. Methylation of MLH1 was associated with
      microsatellite instability in most cases. The number of genes methylated in
      individual lesions increased as cellular atypia increased. In individual
      patients, cancers adjacent to dysplasia had the same epigenetic alterations as
      the less advanced lesions but often had additional methylation of other genes.
      CONCLUSIONS: These findings suggest that epigenetic progression parallels the
      histologic changes observed in the progression of squamous carcinoma of the
      esophagus.

PMID- 16899598
TI  - In vitro drug response and molecular markers associated with drug resistance in
      malignant gliomas.
AB  - PURPOSE: Drug resistance in malignant gliomas contributes to poor clinical
      outcomes. We determined the in vitro drug response profiles for 478 biopsy
      specimens from patients with the following malignant glial histologies:
      astrocytoma (n = 71), anaplastic astrocytoma (n = 39), glioblastoma multiforme (n
      = 259), oligodendroglioma (n = 40), and glioma (n = 69). EXPERIMENTAL DESIGN:
      Samples were tested for drug resistance to 1,3-bis(2-chloroethyl)-1-nitrosourea
      (BCNU), cisplatin, dacarbazine, paclitaxel, vincristine, and irinotecan.
      Biomarkers associated with drug resistance were detected by immunohistochemistry,
      including multidrug resistance gene-1, glutathione S-transferase pi (GSTP1), O(6)
      methylguanine-DNA methyltransferase (MGMT), and mutant p53. RESULTS: In vitro
      drug resistance in malignant gliomas was independent of prior therapy. High-grade
      glioblastomas showed a lower level of extreme drug resistance than low-grade
      astrocytomas to cisplatin (11% versus 27%), temozolomide (14% versus 27%),
      irinotecan (33% versus 53%), and BCNU (29% versus 38%). A substantial percentage
      of brain tumors overexpressed biomarkers associated with drug resistance,
      including MGMT (67%), GSTP1 (49%), and mutant p53 (41%). MGMT and GSTP1
      overexpression was independently associated with in vitro resistance to BCNU,
      whereas coexpression of these two markers was associated with the greatest degree
      of BCNU resistance. CONCLUSIONS: Assessment of in vitro drug response and
      profiles of relevant tumor-associated biomarkers may assist the clinician in
      stratifying patient treatment regimens.

PMID- 16899599
TI  - Prognosis and gene expression profiling of 20q13-amplified breast cancers.
AB  - PURPOSE: Amplification of chromosomal region 20q13 occurs in breast cancer but
      remains poorly characterized. EXPERIMENTAL DESIGN: To establish the frequency of
      20q13 amplification and select the amplified cases to be studied, we used
      fluorescence in situ hybridization of bacterial artificial chromosome probes for
      three 20q13 loci (MYBL2, STK6, ZNF217) on sections of tissue microarrays
      containing 466 primary carcinoma samples. We used Affymetryx whole-genome DNA
      microarrays to establish the gene expression profiles of 20q13-amplified tumors
      and quantitative reverse transcription-PCR to validate the results. RESULTS: We
      found 36 (8%) 20q13-amplified samples. They were distributed in two types: type 1
      tumors showed ZNF217 amplification only, whereas type 2 tumors showed
      amplification at two or three loci. Examination of the histoclinical features of
      the amplified tumors showed two strikingly opposite data. First, type 1 tumors
      were more frequently lymph node-negative tumors but were paradoxically associated
      with a poor prognosis. Second, type 2 tumors were more frequently lymph node
      positive tumors but were paradoxically associated with a good prognosis. Type 1
      and type 2 showed different gene expression profiles. No 20q13 gene could be
      associated with type 1 amplification, whereas several 20q13 genes were
      overexpressed in type 2 tumors. CONCLUSIONS: Our results suggest that amplified
      tumors of types 1 and 2 are two distinct entities resulting from two different
      mechanisms and associated to different prognosis.

PMID- 16899600
TI  - A validated quantitative assay to detect occult micrometastases by reverse
      transcriptase-polymerase chain reaction of guanylyl cyclase C in patients with
      colorectal cancer.
AB  - PURPOSE: Guanylyl cyclase C (GCC), a receptor for bacterial diarrheagenic
      enterotoxins, may be a prognostic and predictive marker to detect occult
      micrometastases in patients undergoing staging for colorectal cancer. However,
      quantification of GCC expression in tissues by the quantitative reverse
      transcription-PCR (qRT-PCR) has not undergone analytic and clinicopathologic
      validation. EXPERIMENTAL DESIGN: A technique to quantify GCC mRNA in tissues
      employing RT-PCR was developed and validated employing external calibration
      standards of RNA complementary to GCC. RESULTS: GCC qRT-PCR exhibited reaction
      efficiencies >92%, coefficients of variations <5%, linearity >6 orders of
      magnitude, and a limit of quantification of >25 copies of GCC cRNA. This assay
      confirmed that GCC mRNA was overexpressed by colorectal tumors from 41 patients,
      which correlated with increased GCC protein quantified by immunohistochemistry.
      Analyses obtained with 164 lymph nodes from patients free of cancer and 15 nodes
      harboring metastases established a threshold for metastatic disease of
      approximately 200 GCC mRNA copies/mug total RNA, with a sensitivity of 93% and
      specificity of 97%. GCC mRNA above that threshold was detected in 76 of 367
      (approximately 21%) nodes free of disease by histopathology from 6 of 23 (26%)
      patients, suggesting the presence of occult micrometastases. CONCLUSIONS:
      Quantifying GCC mRNA in tissues by RT-PCR employing external calibration
      standards is analytically robust and reproducible, with high clinicopathologic
      sensitivity and specificity. This validated assay is being applied to
      approximately 10,000 lymph nodes in a prospective trial to define the sensitivity
      of GCC qRT-PCR for staging patients with colorectal cancer.

PMID- 16899601
TI  - Expression of late cell cycle genes and an increased proliferative capacity
      characterize very early relapse of childhood acute lymphoblastic leukemia.
AB  - PURPOSE: In childhood acute lymphoblastic leukemia (ALL), approximately 25% of
      patients suffer from relapse. In recurrent disease, despite intensified therapy,
      overall cure rates of 40% remain unsatisfactory and survival rates are
      particularly poor in certain subgroups. The probability of long-term survival
      after relapse is predicted from well-established prognostic factors (i.e., time
      and site of relapse, immunophenotype, and minimal residual disease). However, the
      underlying biological determinants of these prognostic factors remain poorly
      understood. EXPERIMENTAL DESIGN: Aiming at identifying molecular pathways
      associated with these clinically well-defined prognostic factors, we did gene
      expression profiling on 60 prospectively collected samples of first relapse
      patients enrolled on the relapse trial ALL-REZ BFM 2002 of the Berlin-Frankfurt
      Munster study group. RESULTS: We show here that patients with very early relapse
      of ALL are characterized by a distinctive gene expression pattern. We identified
      a set of 83 genes differentially expressed in very early relapsed ALL compared
      with late relapsed disease. The vast majority of genes were up-regulated and many
      were late cell cycle genes with a function in mitosis. In addition, samples from
      patients with very early relapse showed a significant increase in the percentage
      of S and G(2)-M phase cells and this correlated well with the expression level of
      cell cycle genes. CONCLUSIONS: Very early relapse of ALL is characterized by an
      increased proliferative capacity of leukemic blasts and up-regulated mitotic
      genes. The latter suggests that novel drugs, targeting late cell cycle proteins,
      might be beneficial for these patients that typically face a dismal prognosis.

PMID- 16899603
TI  - DNA integrity assay: a plasma-based screening tool for the detection of prostate
      cancer.
AB  - PURPOSE: The aim of this study was to evaluate the utility of the DNA integrity
      assay (DIA) as a plasma-based screening tool for the detection of prostate
      cancer. EXPERIMENTAL DESIGN: Blood samples were collected from patients with
      biopsy-proven prostate cancer prior to prostatectomy (n = 123) and processed as
      two-spin plasma preparations. The three control groups included: males <40 years
      old with no history of cancer (group 1, n = 20); cancer-free postprostatectomy
      patients (group 2, n = 25), and patients with a negative prostate biopsy (group
      3, n = 22). DNA in plasma preparations were isolated, hybrid-captured, and DNA
      fragments (200 bp, 1.3, 1.8, and 2.4 kb) were multiplexed in real-time PCR. A
      baseline cutoff was determined for individual fragment lengths to establish a DIA
      score for each patient sample. RESULTS: Patients with prostate cancer (86 of 123;
      69.9%) were determined to have a positive DIA score of >or=7. The DIA results
      from control groups 1, 2, and 3 showed specificities of 90%, 92%, and 68.2%,
      respectively. Of the patients with negative age-adjusted prostate-specific
      antigen (PSA) and prostate cancer, 19 of 30 (63%) had a positive DIA score. The
      area under the receiver operating characteristic curve for DIA was 0.788.
      CONCLUSION: While detecting 69.9% of those with prostate cancer, DIA maintained
      an overall specificity of 68.2% to 92%, a range favorably comparable to that
      currently accepted for PSA (60-70%). The variability in specificity between
      control groups is likely explained by the established 19% to 30% detection of
      prostate cancer on subsequent biopsies associated with control group 3. DIA
      detected 63% of the prostate cancers undetected by currently accepted PSA ranges.

PMID- 16899602
TI  - Hypoxia-inducible factor-1alpha expression predicts a poor response to primary
      chemoendocrine therapy and disease-free survival in primary human breast cancer.
AB  - PURPOSE: To investigate the relationship of hypoxia-inducible factor-1alpha (HIF
      1alpha) tumor expression in predicting the response to epirubicin and disease
      free survival (DFS) in patients with breast cancer enrolled in a single
      institution trial of primary anthracycline and tamoxifen therapy. EXPERIMENTAL
      DESIGN: The expression of HIF-1alpha was assessed by immunohistochemistry in 187
      patients with T(2-4) N(0-1) breast cancer enrolled in a randomized trial
      comparing four cycles of single agent epirubicin versus epirubicin + tamoxifen as
      primary systemic treatment. All patients postoperatively received four cycles of
      the four weekly i.v. CMF regimen (cyclophosphamide, methotrexate, and 5
      fluorouracil). Patients with estrogen receptor (ER)-positive primary tumors also
      underwent 5 years of treatment with adjuvant tamoxifen. Carbonic anhydrase IX
      (CAIX) was also scored as a marker of HIF activity. RESULTS: Overall response to
      therapy progressively decreased with increasing tumor HIF-1alpha (P < 0.05), and
      HIF-1alpha was an independent predictor of response (P < 0.048). HIF-1alpha
      expression was also associated with a significantly shorter DFS (P < 0.02) in all
      patients and in ER-positive but not in ER-negative patients. Furthermore, CAIX
      positivity conferred a significantly shorter DFS (P = 0.02) compared with CAIX
      negative tumors in patients with HIF-1alpha-negative tumors. CONCLUSIONS: HIF
      1alpha expression in patients with breast cancer is a marker of poor therapy
      response and outcome, especially in ER-positive patients. The combination of two
      hypoxia markers has greater utility than assessing just one, and patients with
      hypoxia markers in their tumors may be suitable for administration of drugs that
      reduce HIF-1alpha expression and increase oxygen delivery to the tumor bed before
      starting neoadjuvant therapies.

PMID- 16899604
TI  - Endocan expression and relationship with survival in human non-small cell lung
      cancer.
AB  - PURPOSE: We evaluated the expression of endocan, a soluble lung- and kidney
      selective endothelial cell-specific dermatan sulfate proteoglycan, in non-small
      cell lung tumors compared with normal lung and studied the significance of high
      levels of circulating endocan in patients with non-small cell lung cancer.
      MATERIAL AND METHODS: Endocan and vascular endothelial growth factor mRNA
      expression were evaluated by semiquantitative PCR in tumoral and nontumoral lung
      tissue samples from a first series of 24 patients submitted to curative surgery.
      Relationships between survival, time to tumor progression, and serum levels of
      endocan were evaluated in a second series of 30 previously untreated patients
      addressed for staging. RESULTS: In non-small cell lung cancers, endocan mRNA was
      overexpressed compared with control lung. Immunohistochemistry shows that endocan
      was expressed only by tumor endothelium in all cases, especially in the periphery
      of the tumors, with no differences between adenocarcinoma and squamous cell
      carcinoma. Endocan and vascular endothelial growth factor mRNA expression was
      positively correlated in lung tumors. Serum endocan levels, as well as tumor,
      node, and metastasis status, were correlated with both survival and time to tumor
      progression. However, endocan serum level was not an independent prognostic
      factor due to its correlation with the presence of metastasis. CONCLUSION:
      Endocan is overexpressed in non-small cell lung tumors compared with healthy lung
      and probably represents a response of tumoral endothelium to proangiogenic growth
      factor stimulation. Circulating levels of endocan might reflect tumor angiogenic
      stimulation and present prognostic significance.

PMID- 16899605
TI  - Predicting cancer drug response by proteomic profiling.
AB  - PURPOSE: Accurate prediction of an individual patient's drug response is an
      important prerequisite of personalized medicine. Recent pharmacogenomics research
      in chemosensitivity prediction has studied the gene-drug correlation based on
      transcriptional profiling. However, proteomic profiling will more directly solve
      the current functional and pharmacologic problems. We sought to determine whether
      proteomic signatures of untreated cells were sufficient for the prediction of
      drug response. EXPERIMENTAL DESIGN: In this study, a machine learning model
      system was developed to classify cell line chemosensitivity exclusively based on
      proteomic profiling. Using reverse-phase protein lysate microarrays, protein
      expression levels were measured by 52 antibodies in a panel of 60 human cancer
      cell (NCI-60) lines. The model system combined several well-known algorithms,
      including random forests, Relief, and the nearest neighbor methods, to construct
      the protein expression--based chemosensitivity classifiers. The classifiers were
      designed to be independent of the tissue origin of the cells. RESULTS: A total of
      118 classifiers of the complete range of drug responses (sensitive, intermediate,
      and resistant) were generated for the evaluated anticancer drugs, one for each
      agent. The accuracy of chemosensitivity prediction of all the evaluated 118
      agents was significantly higher (P < 0.02) than that of random prediction.
      Furthermore, our study found that the proteomic determinants for chemosensitivity
      of 5-fluorouracil were also potential diagnostic markers of colon cancer.
      CONCLUSIONS: The results showed that it was feasible to accurately predict
      chemosensitivity by proteomic approaches. This study provides a basis for the
      prediction of drug response based on protein markers in the untreated tumors.

PMID- 16899606
TI  - Early detection of chemoradioresponse in esophageal carcinoma by 3'-deoxy-3'-3H
      fluorothymidine using preclinical tumor models.
AB  - PURPOSE: Early identification of esophageal cancer patients who are responding or
      resistant to combined chemoradiotherapy may lead to individualized therapeutic
      approaches and improved clinical outcomes. We assessed the ability of 3'-deoxy-3'
      (18)F-fluorothymidine positron emission tomography (FLT-PET) to detect early
      changes in tumor proliferation after chemoradiotherapy in experimental models of
      esophageal carcinoma. EXPERIMENTAL DESIGN: The in vitro and ex vivo tumor uptake
      of [(3)H]FLT in SEG-1 human esophageal adenocarcinoma cells were studied at
      various early time points after docetaxel plus irradiation and validated with
      conventional assessments of cellular proliferation [thymidine (Thd) and Ki-67]
      and [(18)F]FLT micro-PET imaging. Imaging-histologic correlation was determined
      by comparing spatial Ki-67 and [(18)F]FLT distribution in autoradiographs.
      Comparison with fluorodeoxyglucose (FDG) was done in all experiments. RESULTS: In
      vitro [(3)H]FLT and [(3)H]Thd uptake rapidly decreased in SEG-1 cells 24 hours
      after docetaxel with a maximal reduction of over 5-fold (P = 0.005). The
      [(3)H]FLT tumor-to-muscle uptake ratio in xenografts declined by 75% compared
      with baseline (P < 0.005) by 2 days after chemoradiotherapy, despite the lack of
      change in tumor size. In contrast, the decline of [(3)H]FDG uptake was gradual
      and less pronounced. Tumor uptake of [(3)H]FLT was more closely correlated with
      Ki-67 expression (r = 0.89, P < 0.001) than was [(3)H]FDG (r = 0.39, P = 0.08).
      Micro-PET images depicted similar trends in reduction of [(18)F]FLT and
      [(18)F]FDG tumor uptake. Autoradiographs displayed spatial correlations between
      [(18)F]FLT uptake and histologic Ki-67 distribution in preliminary studies.
      CONCLUSIONS: FLT-PET is suitable and more specific than FDG-PET for depicting
      early reductions in tumor proliferation that precede tumor size changes after
      chemoradiotherapy.

PMID- 16899607
TI  - Expression of annexin A1 in esophageal and esophagogastric junction
      adenocarcinomas: association with poor outcome.
AB  - PURPOSE: Annexin A1 (ANXA1) is a calcium-binding protein involved in arachidonic
      acid metabolism and epidermal growth factor receptor tyrosine kinase pathway.
      ANXA1 has been implicated in early squamous cell carcinogenesis of esophagus and
      correlates with degree of tumor differentiation. However, the role of ANXA1 in
      esophageal adenocarcinoma is unclear. Our goal was to evaluate ANXA1 expression
      and determine its prognostic significance in adenocarcinoma of the esophagus and
      esophagogastric junction. EXPERIMENTAL DESIGN: This study included 104
      consecutive patients with primary resected esophageal and esophagogastric
      junction adenocarcinomas (11 stage I, 24 stage II, 53 stage III, and 16 stage
      IV). ANXA1 protein expression in each tumor was assessed by immunohistochemical
      staining of tissue microarrays. ANAX1 expression level was classified as high
      (>/=25% of tumor cells with cytoplasmic staining), low (<25% of tumor cells with
      cytoplasmic staining), or negative; and was correlated with clinicopathologic
      features and patients' outcomes. RESULTS: High ANXA1 expression was present in
      39% (41 of 104) of tumors and was associated with higher pathologic T stage (P =
      0.03) and distant metastasis (P = 0.04). High ANXA1 expression correlated with
      increased recurrence rate (P = 0.004) and decreased overall survival (P = 0.003)
      in univariate analysis. In multivariate analysis, ANXA1 expression and pN stage
      significantly correlated with recurrence rate (P = 0.008 and P < 0.001,
      respectively) and overall survival (P = 0.02 and P < 0.001, respectively)
      independent of T stage. CONCLUSION: Our results indicate that high ANXA1
      expression is frequent in esophageal and esophagogastric junction
      adenocarcinomas, correlates with more advanced pathologic T stage and the
      presence of distant metastasis, and is an independent prognostic factor for
      patient survival.

PMID- 16899608
TI  - The prognostic value of circulating tumor cells in patients with melanoma: a
      systematic review and meta-analysis.
AB  - BACKGROUND: The detection of circulating tumor cells (CTC) in patients with
      melanoma represents an appealing prognostic tool, but no consensus exists on this
      topic. We aimed to comprehensively and quantitatively summarize the evidence for
      the use of CTC to predict patients' clinical outcome. METHODS: Fifty-three
      studies enrolling 5,433 patients were reviewed. Correlation of CTC status with
      tumor-node-metastasis disease stage and patients' overall (OS) and progression
      free (PFS) survival was assessed by means of association statistics and meta
      analysis, respectively. RESULTS: CTC status correlated with both tumor-node
      metastasis stage (stage I, 32%; stage II, 41.7%; stage III, 41.1%; stage IV,
      47.4%; P(trend) < 0.0001) and survival (OS: hazard ratio, 2.42; 95% confidence
      interval, 1.7-3.45, P < 0.0001; PFS: hazard ratio, 2.45; 95% confidence interval,
      1.78-3.38; P < 0.0001). However, statistical heterogeneity was significant for
      both OS and PFS, likely underscoring the wide variability in study design.
      Furthermore, CTC positivity rates in early stages were higher and in the
      metastatic setting were lower than expected, which indicates an unsatisfactory
      accuracy of currently available CTC detection assays. CONCLUSIONS: Our findings
      suggest that CTC might have a clinically valuable prognostic power in patients
      with melanoma. However, the heterogeneity of the studies thus far published
      warrants caution not to overestimate the favorable results of pooled data.

PMID- 16899609
TI  - High progesterone receptor expression correlates to the effect of adjuvant
      tamoxifen in premenopausal breast cancer patients.
AB  - PURPOSE: Tamoxifen has long been the drug of choice in adjuvant endocrine therapy
      of steroid hormone receptor-positive breast cancer, and it still remains
      important due to its well-documented beneficial effect. Hormone receptor status
      is often reported as "positive" or "negative" using 10% positive nuclei as a
      cutoff. In this study, we aimed to assess whether a further subclassification of
      hormone receptor status could enhance the treatment predictive value.
      EXPERIMENTAL DESIGN: The immunohistochemical expression of estrogen receptor (ER)
      and progesterone receptor (PR) was quantified in tissue microarrays with tumors
      from 500 premenopausal breast cancer patients previously included in a randomized
      trial of adjuvant tamoxifen compared with an untreated control group. RESULTS:
      Our findings show a gradually increasing tamoxifen effect in tumors with >10% ER
      positive nuclei. However, when analyzing tamoxifen response according to various
      PR fractions, we found that it was primarily patients with tumors showing >75% PR
      positive nuclei that responded to tamoxifen treatment, with an improved
      recurrence-free [relative risk, 0.42 (0.25-0.70); P = 0.001] as well as overall
      [relative risk, 0.49 (0.28-0.84); P = 0.010] survival. CONCLUSIONS: Adjuvant
      tamoxifen improved recurrence-free and overall survival for premenopausal
      patients with tumors showing >75% PR-positive nuclei. No effect could be shown in
      tumors with fewer PR-positive nuclei. The PR was a stronger predictor of
      treatment response than the ER. Based on these findings, we suggest the
      implementation of a fractioned rather than dichotomized immunohistochemical
      evaluation of hormone receptors in clinical practice, possibly with greater
      emphasis on the PR than the ER.

PMID- 16899610
TI  - Phase I trial of sequential low-dose 5-aza-2'-deoxycytidine plus high-dose
      intravenous bolus interleukin-2 in patients with melanoma or renal cell
      carcinoma.
AB  - PURPOSE: The silencing of gene expression through DNA methylation contributes to
      defects in antigen presentation and apoptosis in melanoma and renal cell cancer.
      To determine how a hypomethylating agent would modulate the toxicity and
      antitumor activity of immunotherapy, we initiated a phase I trial of 5-aza-2'
      deoxycytidine (decitabine) plus high-dose interleukin 2 (IL-2). EXPERIMENTAL
      DESIGN: Patients received s.c. decitabine daily x 5 days on weeks 1 and 2 of a 12
      week cycle. High-dose IL-2, consisting of two cycles of IL-2 600,000 IU/kg i.v.
      q8 hours x 14 doses separated by a 2-week break, was administered starting on
      week 3. Decitabine was escalated from 0.1 to 0.25 mg/kg. The hypomethylating
      activity of decitabine was assessed during cycle 1 by measuring hemoglobin F
      levels and changes in DNA methylation in peripheral blood mononuclear cells.
      RESULTS: Twenty-one patients with melanoma or renal cell cancer were enrolled.
      Decitabine did not alter the tolerability of IL-2 but caused grade 4 neutropenia
      in most patients. Grade 4 neutropenia lasting more than 7 days was the only dose
      limiting toxicity, with a trend toward a higher incidence with increasing
      decitabine doses. Infection occurred in only one patient despite the high
      incidence of neutropenia, and granulocyte colony-stimulating factor use in
      several patients expedited neutrophil recovery. Decitabine augmented hemoglobin F
      levels and altered DNA methylation and gene expression in peripheral blood
      mononuclear cells in a dose-independent manner that overlapped with the
      administration of IL-2. Objective responses occurred in 31% of melanoma patients.
      CONCLUSIONS: Decitabine can be safely administered with high-dose IL-2 and may
      enhance the activity of IL-2 in melanoma.

PMID- 16899611
TI  - A phase I study of intravenous LBH589, a novel cinnamic hydroxamic acid analogue
      histone deacetylase inhibitor, in patients with refractory hematologic
      malignancies.
AB  - PURPOSE: LBH589 is a novel histone deacetylase inhibitor that inhibits
      proliferation and induces apoptosis in tumor cell lines. In this phase I study,
      LBH589 was administered i.v. as a 30-minute infusion on days 1 to 7 of a 21-day
      cycle. EXPERIMENTAL DESIGN: Fifteen patients (median age, 63 years; range, 42-87
      years) with acute myeloid leukemia (13 patients), acute lymphocytic leukemia (1
      patient), or myelodysplastic syndrome (1 patient) were treated with LBH589 at the
      following dose levels (mg/m(2)): 4.8 (3 patients), 7.2 (3 patients), 9.0 (1
      patient), 11.5 (3 patient), and 14.0 (5 patients). The levels of histone
      acetylation were measured using quantitative flow cytometry and plasma LBH589
      concentrations were assayed. RESULTS: Four dose-limiting toxicities (grade 3 QTcF
      prolongation) were observed, four at 14.0 mg/m(2) and one at 11.5 mg/m(2). QTcF
      prolongation was asymptomatic and reversed on LBH589 discontinuation. Other
      potentially LBH589-related toxicities included nausea (40%), diarrhea (33%),
      vomiting (33%), hypokalemia (27%), loss of appetite (13%), and thrombocytopenia
      (13%). In 8 of 11 patients with peripheral blasts, transient reductions occurred
      with a rebound following the 7-day treatment period. H3 acetylation increase was
      significant in B-cells (CD19(+); P = 0.02) and blasts (CD34(+); P = 0.04). The
      increase in H2B acetylation was highest in CD19(+) and CD34(+) cells [3.8-fold (P
      = 0.01) and 4.4-fold (P = 0.03), respectively]. The median acetylation of
      histones H2B and H3 in CD34(+) and CD19(+) cells significantly increased on
      therapy as did apoptosis in CD14(+) cells. Area under the curve increased
      proportionally with dose with a terminal half-life of approximately 11 hours.
      CONCLUSION: Intravenous administration of LBH589 was well tolerated at doses
      <11.5 mg/m(2) with consistent transient antileukemic and biological effects.

PMID- 16899612
TI  - Influence of garlic (Allium sativum) on the pharmacokinetics of docetaxel.
AB  - PURPOSE: The herbal supplement garlic (Allium sativum) is commonly used by cancer
      patients. Preclinical studies have shown that allicin, a major component of
      garlic, may affect cytochrome P450 3A4 (CYP3A4) activity. This study examines the
      influence of garlic supplementation on the pharmacokinetics of docetaxel, a
      CYP3A4 substrate. EXPERIMENTAL DESIGN: Women with metastatic breast cancer were
      treated with docetaxel (30 mg/m(2)) given weekly for 3 of 4 weeks. Three days
      after the initial dose of docetaxel, patients received 600 mg of garlic twice
      daily for 12 consecutive days. Docetaxel pharmacokinetics were assessed during
      the first three administrations. RESULTS: In 10 evaluable patients, the mean
      baseline clearance of docetaxel was 30.8 L/h/m(2) [95% confidence intervals (95%
      CI), 16.7-44.9]. Coadministration of garlic reduced mean clearance of docetaxel
      to 23.7 L/h/m(2) (95% CI, 15.5-31.8) and 20.0 L/h/m(2) (95% CI, 13.3-26.7) on
      days 8 and 15, respectively (P = 0.17). Additional pharmacokinetic variables of
      docetaxel, including peak concentration (P = 0.79), area under the curve (P =
      0.36), volume of distribution (P = 0.84), and half-life (P = 0.36), were also not
      statistically significantly different. The mean area under the curve ratio
      between day 15 and day 1 was 3.74 in three individuals with the CYP3A5*1A/*1A
      genotype (all African American) compared with 1.02 in six individuals with the
      CYP3A5*3C/*3C genotype (all Caucasian). CONCLUSIONS: This study indicates that
      garlic does not significantly affect the disposition of docetaxel. However, it
      cannot be excluded that garlic decreases the clearance of docetaxel in patients
      carrying a CYP3A5*1A allele.

PMID- 16899613
TI  - Effect of human leukocyte antigen class I expression of tumor cells on outcome of
      intravesical instillation of bacillus calmette-guerin immunotherapy for bladder
      cancer.
AB  - PURPOSE: Various immune systems play important roles in the clinical efficacy of
      intravesical Bacillus Calmette-Guerin (BCG) instillation for bladder cancer.
      However, human leukocyte antigen (HLA) class I molecules on tumor cells and
      various immune system cells infiltrating to/around the tumor have not been
      evaluated, although many prognostic factors, including clinical, pathologic, and
      molecular ones, have been investigated. The aim of this study was to determine
      immunologic prognostic factors of BCG immunotherapy for bladder cancer.
      EXPERIMENTAL DESIGN: Immunohistochemical staining for HLA class I, CD4, CD8,
      CD20, CD68, TIA-1, S-100, and FOXP3 was carried out on specimens from 30 patients
      who underwent BCG immunotherapy from whom both pretreatment and posttreatment
      specimens were obtained. We did univariate and multivariate analyses of factors
      affecting recurrence-free survival. The positive, weakly positive, and negative
      groups of cells that infiltrated to/around the tumor were compared with
      recurrence-free survival using the Kaplan-Meier method and log-rank test.
      RESULTS: HLA class I was a significant prognostic factor both in univariate and
      multivariate analyses. The 5-year recurrence-free survivals of the patients with
      HLA class I-positive tumors and those with HLA class I-negative tumors were 55.7%
      and 19.1%, respectively (P = 0.019). There was a significant association between
      infiltration of CD8, CD20, and CD68-positive cells after BCG therapy and
      therapeutic effects. CONCLUSIONS: Our data show that expression of HLA class I
      molecules on tumor cells contributes significantly to the therapeutic effect of
      BCG immunotherapy for bladder cancer. It is suggested that CTLs may be one of
      main effectors in this therapy.

PMID- 16899614
TI  - Increased bioavailability of intravenous versus oral CI-1033, a pan erbB tyrosine
      kinase inhibitor: results of a phase I pharmacokinetic study.
AB  - PURPOSE: In phase I studies with oral CI-1033, dose-limiting toxicities were
      primarily gastrointestinal, supporting the exploration of i.v. dosing to achieve
      optimal drug exposures by increasing bioavailability. EXPERIMENTAL DESIGN: Fifty
      three patients with advanced nonhematologic malignancies received i.v. CI-1033
      via 30-minute infusions (10-500 mg) on a thrice-weekly schedule. Pharmacokinetic
      samples were collected on days 1 and 8 and evaluated using noncompartmental
      analysis. RESULTS: Dose levels evaluated were 10, 20, 30, 45, 67.5, 100, 150,
      225, 337.5, and 500 mg. The maximum administered dose was 500 mg, whereas the
      maximum tolerated dose was 225 mg. The most common treatment-related grade 1 to 2
      adverse events were rashes (38% of patients), nausea (17%), vomiting (17%),
      stomatitis (14%), and diarrhea (13%). Most common grade 3 adverse events were
      hypersensitivity reactions (7.5%), rashes (3.8%), and diarrhea (3.8%). No grade 4
      toxicities were observed. Ten of the 53 (19%) patients had disease stabilization
      at their first efficacy evaluation visit (including two with minor responses). A
      5- to 10-fold increase in i.v. C(max) was noted with a 3-fold increase in AUC
      compared with oral CI-1033 at equivalent doses. Treatment-related
      gastrointestinal adverse events were notably less frequent with this i.v.
      regimen. CONCLUSIONS: CI-1033 was safely given i.v. up to 225 mg/dose on a thrice
      weekly schedule, with evidence of antitumor activity. At equivalent doses, the
      bioavailability of i.v. CI-1033 is thrice that of the oral formulation. Treatment
      with i.v. CI-1033 is feasible and may be warranted when increased drug exposures
      are desired.

PMID- 16899615
TI  - An in vivo platform for translational drug development in pancreatic cancer.
AB  - Effective development of targeted anticancer agents includes the definition of
      the optimal biological dose and biomarkers of drug activity. Currently available
      preclinical models are not optimal to this end. We aimed at generating a model
      for translational drug development using pancreatic cancer as a prototype.
      Resected pancreatic cancers from 14 patients were xenografted and expanded in
      successive groups of nude mice to develop cohorts of tumor-bearing mice suitable
      for drug therapy in simulated early clinical trials. The xenografted tumors
      maintain their fundamental genotypic features despite serial passages and
      recapitulate the genetic heterogeneity of pancreatic cancer. The in vivo platform
      is useful for integrating drug screening with biomarker discovery. Passages of
      tumors in successive cohorts of mice do not change their susceptibility to
      anticancer agents and represent a perpetual live bank, facilitating the
      application of new technologies that will result in the creation of an integrated
      stable database of tumor-drug response data and biomarkers.

PMID- 16899617
TI  - Mutations within the kinase domain and truncations of the epidermal growth factor
      receptor are rare events in bladder cancer: implications for therapy.
AB  - PURPOSE: It has previously been reported that the patient response to gefitinib
      depends on the presence of mutations within the kinase domain of epidermal growth
      factor receptor (EGFR) or the expression of its truncated form, EGFR variant III
      (EGFRvIII). The focus of this study was to determine if these alterations are
      present within the tyrosine kinase and ligand-binding domain of EGFR in
      urothelial carcinoma. EXPERIMENTAL DESIGN: The kinase domain found within exons
      18 to 21 of the EGFR from 11 bladder cancer cell lines and 75 patient tumors were
      subjected to automated sequencing. EGFRvIII expression was determined by
      immunohistochemistry using a urothelial carcinoma tissue microarray, and its
      expression was subsequently verified by reverse transcription PCR, real-time PCR,
      and Western blot analysis, using an EGFRvIII-transfected glioblastoma cell line
      and glioblastoma tumors as positive controls. RESULTS: Our analysis failed to
      detect mutations within the tyrosine kinase domain of EGFR in the 11 cell lines
      and 75 patients tested. The initial analysis of EGFRvIII expression by
      immunohistochemistry revealed that at least 50% of the patient tumors expressed
      EGFRvIII in a urothelial carcinoma tissue microarray. Conflicting reports exist,
      however, regarding the extent of EGFRvIII expression in tissues owing to the
      specificity of the antibodies and the methodologies used. Therefore, we sought to
      validate this observation by reverse transcription PCR, real-time PCR, and
      Western blot analysis. In these assays, none of the samples were positive for
      EGFRvIII except for control transfectants and glioblastomas. CONCLUSIONS: When
      our results are taken together, we conclude that alterations within the tyrosine
      kinase domain and expression of EGFRvIII are rare events in bladder cancer. The
      present study has clinical implications in selecting tyrosine kinase inhibitors
      for the therapy of urothelial carcinoma.

PMID- 16899616
TI  - Effect of altering dietary omega-6/omega-3 fatty acid ratios on prostate cancer
      membrane composition, cyclooxygenase-2, and prostaglandin E2.
AB  - PURPOSE: To determine whether altering the dietary content of omega-6 (n-6) and
      omega-3 (n-3) polyunsaturated fatty acids affects the growth of androgen
      sensitive prostate cancer xenografts, tumor membrane fatty acid composition, and
      tumor cyclooxygenase-2 and prostaglandin E(2) (PGE(2)) levels. EXPERIMENTAL
      DESIGN: Individually caged male severe combined immunodeficiency mice were fed
      isocaloric 20% kcal fat diets with the fat derived either primarily from n-6
      fatty acids (n-6 group) or with the fat consisting of n-6 and n-3 fatty acids in
      a ratio of 1:1 (n-3 group), and injected s.c. with Los Angeles Prostate Cancer 4
      (LAPC-4) cells. Tumor volumes and mouse weights were measured weekly, caloric
      intake was measured 3 days per week, and tumors and serum were harvested at 8
      weeks postinjection. RESULTS: Tumor growth rates, final tumor volumes, and serum
      prostate-specific antigen levels were reduced in the n-3 group relative to the n
      6 group. The n-3 group tumors had decreased proliferation (Ki67 staining) and
      increased apoptosis (terminal nucleotidyl transferase-mediated nick end labeling
      staining). In vitro proliferation of LAPC-4 cells in medium containing n-3 group
      serum was reduced by 22% relative to LAPC-4 cells cultured in medium containing
      serum from the n-6 group. The n-6/n-3 fatty acid ratios in serum and tumor
      membranes were lower in the n-3 group relative to the n-6 group. In addition, n-3
      group tumors had decreased cyclooxygenase-2 protein and mRNA levels, an 83%
      reduction in PGE(2) levels, and decreased vascular endothelial growth factor
      expression. CONCLUSION: These results provide a sound basis for clinical trials
      evaluating the effect of dietary n-3 fatty acids from fish oil on tumor PGE(2)
      and membrane fatty acid composition, and serum and tumor biomarkers of
      progression in men with prostate cancer.

PMID- 16899618
TI  - Intratumoral therapy with IL13-PE38 results in effective CTL-mediated suppression
      of IL-13Ralpha2-expressing contralateral tumors.
AB  - PURPOSE: IL13-PE38, a targeted cytotoxin comprised of interleukin 13 (IL-13) and
      a mutated form of Pseudomonas exotoxin, induces specific killing of tumor cells
      expressing abundant levels of the IL-13Ralpha2 chain. We hypothesized that tumor
      cells killed by the cytotoxin may release antigens and/or apoptotic bodies when
      cells are dying, which then induce adoptive immunity, and that the PE38 portion
      of IL13-PE38 may act as a stimulant for the induction of a CTL response.
      EXPERIMENTAL DESIGN: To test this hypothesis, we established D5 melanoma tumors
      with or without expression of the IL-13Ralpha2 chain in both flanks of C57BL/6
      mice, and then IL13-PE38 was injected in the right flank tumors only. RESULTS AND
      CONCLUSIONS: When animals with IL-13Ralpha2-expressing D5 tumor (right) were
      injected with IL13-PE38, right flank tumors expressing the IL-13Ralpha2 chain not
      only showed dramatic regression but contralateral tumors (left flank) also showed
      tumor regression. Cell depletion experiments in tumor-bearing animals indicated
      that both CD8(+) and CD4(+) T cells contribute to the regression of contralateral
      tumors through CTL activation in the periphery and cellular infiltration into
      tumors. In addition, intratumoral treatment into s.c. tumors of mice bearing
      metastatic lung tumors with IL13-PE38 showed not only the reduction of treated
      s.c. tumor but also the reduction of lung metastasis. Thus, IL13-PE38 mediates an
      antitumor effect not only directly but also indirectly by inducing a host CD8(+)
      T cell immune response. Accordingly, targeted cytotoxins may be used to treat
      local disease even if they cannot be administered systemically, and yet may still
      induce a reasonable systemic antitumor response.

PMID- 16899619
TI  - Valproic Acid prolongs survival time of severe combined immunodeficient mice
      bearing intracerebellar orthotopic medulloblastoma xenografts.
AB  - PURPOSE: To develop novel orthotopic xenograft models of medulloblastoma in
      severe combined immunodeficient mice and to evaluate the in vivo antitumor
      efficacy of valproic acid. EXPERIMENTAL DESIGN: Orthotopic xenografts were
      developed by injecting 10(3) to 10(5) tumor cells from four medulloblastoma cell
      lines (D283-MED, DAOY, MHH-MED-1, and MEB-MED-8A) into the right cerebellum of
      severe combined immunodeficient mice. Animals were then examined for
      reproducibility of tumorigenicity, cell number-survival time relationship, and
      histopathologic features. Tumor growth was monitored in vivo by serially
      sectioning the xenograft brains at 2, 4, 6, and 8 weeks postinjection. Valproic
      acid treatment, administered at 600 microg/h for 2 weeks via s.c. osmotic
      minipumps, was initiated 2 weeks after injection of 10(5) medulloblastoma cells,
      and treated and untreated animals were monitored for differences in survival.
      Changes in histone acetylation, proliferation, apoptosis, differentiation, and
      angiogenesis in xenografts were also evaluated. RESULTS: Tumorigenicity was
      maintained at 100% in D283-MED, DAOY, and MHH-MED-1 cell lines. These cerebellar
      xenografts displayed histologic features and immunohistochemical profiles
      (microtubule-associated protein 2, glial fibrillary acidic protein, and vimentin)
      similar to human medulloblastomas. Animal survival time was inversely correlated
      with injected tumor cell number. Treatment with valproic acid prolonged survival
      time in two (D283-MED and MHH-MED-1) of the three models and was associated with
      induction of histone hyperacetylation, inhibition of proliferation and
      angiogenesis, and enhancement of apoptosis and differentiation. CONCLUSION: We
      have developed intracerebellar orthotopic models that closely recapitulated the
      biological features of human medulloblastomas and characterized their in vivo
      growth characteristics. Valproic acid treatment of these xenografts showed potent
      in vivo anti-medulloblastoma activity. These xenograft models should facilitate
      the understanding of medulloblastoma pathogenesis and future preclinical
      evaluation of new therapies against medulloblastoma.

PMID- 16899620
TI  - Synergistic antitumor activity of taxol and immunotoxin SS1P in tumor-bearing
      mice.
AB  - PURPOSE: To investigate the combined antitumor activity in mice of immunotoxin
      SS1P and Taxol. METHODS: Immunodeficient mice were implanted with A431/K5 tumors
      expressing mesothelin. Established tumors were treated i.v. with immunotoxin SS1P
      alone, i.p. with Taxol alone, or with the two agents together. SS1P was
      radiolabeled with (111)In and used to study the effect of Taxol on its uptake by
      A431/K5 tumors. RESULTS: Using doses at which either agent alone caused
      stabilization of tumor growth, the combination was synergistic causing long
      lasting complete remissions in many animals. In contrast, synergy was not
      observed when the same cells were treated with these agents in vitro. Tumor
      uptake of (111)In-SS1P was not affected by treatment with Taxol. CONCLUSION: The
      combination of Taxol and SS1P exerts a synergistic antitumor effect in animals
      but not in cell culture. This effect is not secondary to increased tumor uptake
      of the immunotoxin. Synergy could be due to improved immunotoxin distribution
      within the tumor or could involve factors released by other cell types in the
      tumors.

PMID- 16899621
TI  - Minicircle-IFNgamma induces antiproliferative and antitumoral effects in human
      nasopharyngeal carcinoma.
AB  - PURPOSE: The aims of this work were to investigate the antitumor effect of
      IFNgamma gene transfer on human nasopharyngeal carcinoma (NPC) and to assess the
      potential of minicircle vector for antitumor gene therapy. EXPERIMENTAL DESIGN:
      We developed a recombinant minicircle vector carrying the human IFNgamma gene and
      evaluated the effects of minicircle-mediated IFNgamma gene transfer on NPC cell
      lines in vitro and on xenografts in vivo. RESULTS: Relative to p2PhiC31-IFNgamma,
      minicircle-mediated IFNgamma gene transfer in vitro resulted in 19- to 102-fold
      greater IFNgamma expression levels in transfected cells (293, NIH 3T3, CNE-1, CNE
      2, and C666-1) and inhibited the growth of CNE-1, CNE-2, and C666-1 cells more
      efficiently, reducing relative growth rates to 7.1 +/- 1.6%, 2.7 +/- 1.0%, and
      6.1 +/- 1.6%, respectively. Flow cytometry and caspase-3 activity assays
      suggested that the antiproliferative effects of IFNgamma gene transfer on NPC
      cell lines could be attributed to G(0)-G(1) arrest and apoptosis. Minicircle
      mediated intratumoral IFNgamma expression in vivo was 11 to 14 times higher than
      p2PhiC31-IFNgamma in CNE-2- and C666-1-xenografted mice and lasted for 21 days.
      Compared with p2PhiC31-IFNgamma treatment, minicircle-IFNgamma treatment
      significantly increased survival and achieved inhibition rates of 77.5% and 83%,
      respectively. CONCLUSIONS: Our data indicate that IFNgamma gene transfer exerts
      antiproliferative effects on NPC cells in vitro and leads to a profound antitumor
      effect in vivo. Minicircle-IFNgamma is more efficient than corresponding
      conventional plasmids due to its capability of mediating long-lasting high levels
      of IFNgamma gene expression. Therefore, minicircle-mediated IFNgamma gene
      transfer is a promising novel approach in the treatment of NPC.

PMID- 16899622
TI  - Low-dose combretastatin A4 phosphate enhances the immune response of tumor hosts
      to experimental colon carcinoma.
AB  - PURPOSE: Although there is a need to enhance the therapeutic efficiency in cancer
      by combining immunotherapeutic procedures with other therapy, combination with
      chemotherapy is complicated due to immunosuppressive effects of most
      chemotherapeutic drugs. The purpose of this investigation was to study whether
      combining tumor cell immunization with the vascular targeting drug combretastatin
      A4 phosphate (CA4P) would enhance tumor retardation and/or affect the antitumor
      immune response. EXPERIMENTAL DESIGN: Rats with intrahepatic colon carcinoma were
      immunized weekly with IL-18/IFNgamma-transfected tumor cells, starting day 9, and
      were treated with a low-dose CA4P (2 mg/kg, 5 days a week starting day 7). The
      effect of CA4P was studied on tumor growth and on immune reactivity in vitro.
      RESULTS: Rats with preexisting tumor, immunized and treated with low-dose CA4P,
      had a significantly retarded tumor growth compared with rats receiving CA4P or
      immunization alone. Splenocytes from rats treated with this combination had a
      significantly enhanced antitumor immune response compared with splenocytes from
      control rats. Exposure of nonadherent splenocytes to CA4P in vitro did not
      enhance their proliferation. However, 3-hour pretreatment of adherent splenocytes
      with 0.3 microg/mL CA4P significantly enhanced proliferation and IFNgamma
      production of admixed nonadherent splenocytes, partly due to nitric oxide
      reduction. Combining the nitric oxide synthase inhibitor N-nitro-l-arginine
      methyl ester with CA4P and immunization further retarded tumor growth.
      CONCLUSION: Concomitant treatment of rats with progressively growing tumor with
      immunization and low-dose CA4P significantly enhances the therapeutic effect as
      compared with either treatment alone and results in an enhanced antitumor immune
      reactivity.

PMID- 16899623
TI  - Antisense to cyclin D1 inhibits vascular endothelial growth factor-stimulated
      growth of vascular endothelial cells: implication of tumor vascularization.
AB  - PURPOSE: Our aim was to determine the effects of cyclin D1 inhibition on tumor
      associated neovascularization and endothelial cell growth. EXPERIMENTAL DESIGN:
      We have generated adenovirus system for antisense to cyclin D1 (AS CyD1) and
      evaluated in vitro and in vivo effects. Small interfering RNA against cyclin D1
      was also used to analyze cyclin D1 inhibition-associated vascular endothelial
      growth factor (VEGF) regulation. RESULTS: The xenografts treated with adenoviral
      AS CyD1 showed less vessel density and displayed smaller tumor size in colon
      cancer cell lines HCT116 and DLD1. In vitro studies indicated that AS CyD1
      decreased VEGF protein expression in DLD1 but not in HCT116. Cyclin D1 small
      interfering RNA caused a decrease in VEGF expression at protein and RNA levels in
      DLD1. A modest decrease was noted in the VEGF promoter activity, with
      inactivation of the STAT3 transcription factor through dephosphorylation. On the
      hand, the cyclin D1 inhibition plus STAT3 inhibitor markedly decreased VEGF
      expression in HCT116, although VEGF did not change by the STAT3 inhibitor alone.
      In cultures of human umbilical vein endothelial cells (HUVEC), VEGF augmented
      cyclin D1 expression and cell growth. AS CyD1 significantly inhibited HUVEC
      growth even in the presence of VEGF. AS CyD1 also significantly suppressed in
      vitro tube formation in VEGF-treated HUVEC and in vivo macroaneurysm formation in
      VEGF-treated Matrigel plug. CONCLUSIONS: Our results suggest that cyclin D1 may
      play a role in the maintenance of VEGF expression and that AS CyD1 could be
      potentially useful for targeting both cancer cells and their microenvironment of
      tumor vessels.

PMID- 16899624
TI  - The combination of ionizing radiation and peripheral vaccination produces long
      term survival of mice bearing established invasive GL261 gliomas.
AB  - PURPOSE: High-grade glioma treatment includes ionizing radiation therapy. The
      high invasiveness of glioma cells precludes their eradication and is responsible
      for the dismal prognosis. Recently, we reported the down-regulation of MHC class
      I (MHC-I) products in invading tumor cells in human and mouse GL261 gliomas.
      Here, we tested the hypothesis that whole-brain radiotherapy (WBRT) up-regulates
      MHC-I expression on GL261 tumors and enhances the effectiveness of immunotherapy.
      EXPERIMENTAL DESIGN: MHC-I molecule expression on GL261 cells was analyzed in
      vitro and in vivo by flow cytometry and immunohistochemistry, respectively. To
      test the response of established GL261 gliomas to treatment, mice with measurable
      (at CT imaging) brain tumors were randomly assigned to four groups receiving (a)
      no treatment, (b) WBRT in two fractions of 4 Gy, (c) vaccination with irradiated
      GL261 cells secreting granulocyte-macrophage colony-stimulating factor, or (d)
      WBRT and vaccination. Endpoints were tumor response and survival. RESULTS: An
      ionizing radiation dose of 4 Gy maximally up-regulated MHC-I molecules on GL261
      cells in vitro. In vivo, WBRT induced the expression of the beta2-microglobulin
      light chain subunit of the MHC class I complex on glioma cells invading normal
      brain and increased CD4+ and CD8+ T cell infiltration. However, the survival
      advantage obtained with WBRT or vaccination alone was minimal. In contrast, WBRT
      in combination with vaccination increased long-term survival to 40% to 80%,
      compared with 0% to 10% in the other groups (P < 0.002). Surviving animals showed
      antitumor immunity by rejecting challenge tumors. CONCLUSION: Ionizing radiation
      can be successfully combined with peripheral vaccination for the treatment of
      established high-grade gliomas.

PMID- 16899626
TI  - Hypoxia-inducible factor-1 inhibition in combination with temozolomide treatment
      exhibits robust antitumor efficacy in vivo.
AB  - PURPOSE: Inhibiting hypoxia-inducible factor-1 (HIF-1) represents a unique
      mechanism for cancer therapy. It is conceived that HIF-1 inhibitors may synergize
      with many classes of cancer therapeutic agents, such as angiogenesis inhibitors
      and cytotoxic drugs, to achieve a more robust tumor response. However, these
      hypotheses have not been rigorously tested in tumor models in vivo. The present
      study was carried out to evaluate the antitumor efficacy of combining HIF-1
      inhibition with angiogenesis inhibitors or cytotoxic agents. EXPERIMENTAL DESIGN:
      Using a D54MG-derived tumor model that allows knockdown of HIF-1alpha on
      doxycycline treatment, we examined the tumor responses to chemotherapeutic
      agents, including the angiogenesis inhibitor ABT-869 and cytotoxic agents 1,3
      bis(2-chloroethyl)-1-nitrosourea and temozolomide, in the presence or absence of
      an intact HIF-1 pathway. RESULTS: Surprisingly, inhibiting HIF-1 in tumors
      treated with the angiogenesis inhibitor ABT-869 did not produce much added
      benefit compared with ABT-869 treatment alone, suggesting that the combination of
      an angiogenesis inhibitor with a HIF-1 inhibitor may not be a robust therapeutic
      regimen. In contrast, the cytotoxic drug temozolomide, when used in combination
      with HIF-1alpha knockdown, exhibited a superadditive and likely synergistic
      therapeutic effect compared with the monotherapy of either treatment alone in the
      D54MG glioma model. CONCLUSIONS: Our results show that the DNA alkylating agent
      temozolomide exhibits robust antitumor efficacy when used in combination with HIF
      1 inhibition in D54MG-derived tumors, suggesting that the combination of
      temozolomide with HIF-1 inhibitors might be an effective regimen for cancer
      therapy. In addition, our results also show that the RNA interference-based
      inducible knockdown model can be a valuable platform for further evaluation of
      the combination treatment of other cancer therapeutics with HIF-1 inhibition.

PMID- 16899625
TI  - Temozolomide-mediated radiation enhancement in glioblastoma: a report on
      underlying mechanisms.
AB  - PURPOSE: In this study, we investigated the mechanisms by which temozolomide
      enhances radiation response in glioblastoma cells. EXPERIMENTAL DESIGN: Using a
      panel of four primary human glioblastoma cell lines with heterogeneous O(6)
      methylguanine-DNA methyltransferase (MGMT) protein expression, normal human
      astrocytes, and U87 xenografts, we investigated (a) the relationship of MGMT
      status with efficacy of temozolomide-based chemoradiation using a panel of in
      vitro and in vivo assays; (b) underlying mechanisms by which temozolomide
      enhances radiation effect in glioblastoma cells; and (c) strategies to overcome
      resistance to radiation + temozolomide. RESULTS: Temozolomide enhances radiation
      response most effectively in glioblastomas without detectable MGMT expression. On
      concurrent radiation + temozolomide administration in MGMT-negative
      glioblastomas, there seems to be decreased double-strand DNA (dsDNA) repair
      capacity and enhanced dsDNA damage compared either with radiation alone or with
      sequentially administered temozolomide. Our data suggest that O(6)-benzylguanine
      can enhance the antitumor effects of concurrent radiation + temozolomide in MGMT
      positive cells by enhancing apoptosis and the degree of dsDNA damage. O(6)
      Benzylguanine was most effective when administered concurrently with radiation +
      temozolomide and had less of an effect when administered with temozolomide in the
      absence of radiation or when administered sequentially with radiation. Our in
      vivo data using U87 xenografts confirmed our in vitro findings. CONCLUSIONS: The
      present study shows that temozolomide enhances radiation response most
      effectively in MGMT-negative glioblastomas by increasing the degree of radiation
      induced double-strand DNA damage. In MGMT-positive glioblastomas, depletion of
      MGMT by the addition of O(6)-benzylguanine significantly enhances the antitumor
      effect of concurrent radiation + temozolomide. These are among the first data
      showing mechanisms of synergy between radiation and temozolomide and the effect
      of MGMT.

PMID- 16899627
TI  - Growth-inhibitory effects of human anti-insulin-like growth factor-I receptor
      antibody (A12) in an orthotopic nude mouse model of anaplastic thyroid carcinoma.
AB  - PURPOSE: The insulin-like growth factor-I receptor (IGF-IR) and its ligands have
      been implicated in the pathogenesis and progression of various cancers, including
      those arising in the thyroid gland. We therefore evaluated whether the IGF-IR
      could serve as a potential target for therapy of anaplastic thyroid carcinoma
      (ATC). EXPERIMENTAL DESIGN: The expression and activation of the IGF-IR and some
      of its downstream signaling pathway components were evaluated in both human
      thyroid cancer specimens and thyroid cancer cell lines. The therapeutic potential
      of a humanized monoclonal antibody (A12) directed against IGF-IR was assessed in
      vitro and in vivo in an orthotopic model of ATC. Tumor volume and overall
      survival time were analyzed to evaluate the efficacy of A12 in vivo. RESULTS: IGF
      IR was overexpressed in 94% of the thyroid cancers. Blockade of IGF-IR with A12
      was effective in attenuating IGF-IR signaling both in vitro and in vivo. However,
      the inhibitory effects of A12 on cell proliferation were cell line dependent, as
      those ATC cell lines that had detectable levels of pIGF-IR were more sensitive to
      A12 treatment. A12 was equally effective in vivo, where it brought approximately
      57% (P = 0.041) inhibition in tumor volume. The concomitant use of A12 and
      irinotecan produced additive effects and resulted in a 93% (P < 0.001) reduction
      in tumor volume. Blocking IGF-IR blocked Akt phosphorylation and decreased
      proliferation and microvessel density but increased apoptosis within the tumor
      xenografts. Our results also highlighted a previously undefined IGF-IR-mediated
      antiangiogenic effect on tumor-associated endothelium in thyroid cancers.
      CONCLUSION: Blocking the IGF-IR with A12 seems to be a potential avenue for
      treating patients with ATC by its direct antitumor effects and its effects on the
      tumor vasculature.

PMID- 16899628
TI  - Effects of long-term rofecoxib on gastric intestinal metaplasia: results of a
      randomized controlled trial.
AB  - PURPOSE: Gastric cancer and its premalignant gastric lesion, intestinal
      metaplasia (IM), frequently express cyclooxygenase-2 (COX-2) at high levels. We
      tested whether long-term use of specific COX-2 inhibitors regress gastric IM.
      EXPERIMENTAL DESIGN: This is a double-blind, randomized, placebo-controlled
      trial. Individuals with confirmed IM and Helicobacter pylori clearance were
      randomized to receive rofecoxib 25 mg daily or placebo. Endoscopy was done at
      baseline, at the end of year 1, and at the end of year 2, with multiple biopsies
      taken from the antrum and corpus. The primary end point was the proportion of
      subjects with regression of IM. Secondary end points were the severity of other
      histologic variables and the proportion of subjects with complete regression of
      IM. RESULTS: Two-hundred and thirteen subjects with confirmed IM were randomized.
      The proportion of subjects with the regression of IM did not differ significantly
      between rofecoxib and placebo groups (antrum, 24.5% versus 26.9%; P = 0.74;
      corpus, 4.3% versus 2.2%; P = 0.68). Patients on rofecoxib (19.1%) and on placebo
      (16.1%) had no IM detected in the stomach (P = 0.59). There was also no
      significant difference in the severity of IM between the two treatment groups (P
      >or= 0.3). CONCLUSIONS: There was no trend to suggest that treatment with
      rofecoxib for 2 years resulted in the regression of gastric IM. Although our
      findings cast doubt on the reversibility of gastric IM by COX-2 inhibitor,
      further studies are needed to establish the role of COX-2 inhibitors in different
      stages of gastric carcinogenesis.

PMID- 16899629
TI  - Expression of carcinoembryonic antigen cell adhesion molecule 6 oncoprotein in
      atypical ductal hyperplastic tissues is associated with the development of
      invasive breast cancer.
AB  - BACKGROUND: Epidemiologic studies have established that women with prior atypical
      ductal hyperplastic (ADH) lesions have a 5-fold increased risk of developing
      invasive breast cancer (IBC). However, there is currently no means of identifying
      a subclass of ADH from women who will most likely develop cancer. The purpose of
      this study is to investigate whether elevated expression of carcinoembryonic
      antigen cell adhesion molecule 6 (CEACAM6) in ADH tissues is associated with the
      development of IBC. METHODS: A retrospective study was conducted with archival
      ADH tissues and clinical information on the development/nondevelopment of IBC.
      The control group was ADH from patients who had no prior history of IBC and did
      not develop cancer within 5 years after the diagnosis of ADH (n = 44). The test
      group was ADH from patients who either developed cancer concurrently or
      subsequently after diagnosis (ADHC; n = 44). The expression of CEACAM6 was
      studied by immunohistochemistry and the results were statistically analyzed for
      significant association to develop cancer (P value), specificity, sensitivity,
      positive predictive value, and negative predictive value. RESULTS: Of the 44
      control ADH tissues from patients with no history of cancer, 9 were positive for
      CEACAM6. Among the ADHC tissues, 40 of 44 samples were positive. Statistical
      analysis of CEACAM6 expression data showed a significant association between its
      expression and cancer development, high sensitivity, specificity, positive
      predictive value, and negative predictive value. CONCLUSIONS: The expression of
      CEACAM6 in ADH lesions is strongly associated with the development of IBC,
      therefore, it can be applied as a diagnostic marker either singly or in
      combination with other marker(s) to predict IBC development in women with ADH
      lesions. It could also be a potential molecular therapeutic target for preventing
      IBC.

PMID- 16899630
TI  - Genetic effect of ERCC1 codon 118 polymorphism and confounding factors.

PMID- 16899631
TI  - Loss of binocular responses and reduced retinal convergence during the period of
      retinogeniculate axon segregation.
AB  - In the developing mammalian visual system, axon terminals from the two eyes
      overlap in the dorsal lateral geniculate nucleus (LGN) but then undergo a period
      of refinement and segregate to form distinct eye-specific domains. We report on
      the changes in synaptic transmission that occur in rodent LGN during the period
      of retinogeniculate axon segregation by using anterograde labeling techniques in
      conjunction with an in vitro preparation where large segments of each optic nerve
      are preserved. Anterograde labeling of retinal projections in early postnatal day
      (P) rats with cholera toxin beta subunit indicated an age-related recession in
      uncrossed retinal projections. Between P2 and P5 uncrossed projections occupied
      as much as 50% of the LGN and overlapped substantially with crossed projections.
      Between the first and second postnatal week uncrossed projections receded, so by
      P14 they assumed an adultlike profile occupying 15-20% of LGN and showed little
      or no overlap with crossed projections. The postsynaptic responses of LGN cells
      evoked by the separate stimulation of each optic nerve indicated that before P14,
      many relay cells were binocularly innervated and received at least four to six
      inputs from each eye. However, these features of retinogeniculate connectivity
      were transient and their attrition occurred in concert with a retraction of
      retinal arbors into nonoverlapping, eye-specific regions. By P18 cells were
      monocularly innervated and received input from one to three retinal ganglion
      cells. These results provide a better understanding of the underlying changes in
      synaptic circuitry that occur during the anatomical segregation of retinal inputs
      into eye-specific territories.

PMID- 16899632
TI  - Intrinsic and synaptic mechanisms determining the timing of neuron population
      activity during hippocampal theta oscillation.
AB  - Hippocampal theta (3-8 Hz) is a major electrophysiological activity in rodents,
      which can be found in primates and humans as well. During theta activity,
      pyramidal cells and different classes of interneurons were shown to discharge at
      different phases of the extracellular theta. A recent in vitro study has shown
      that theta-frequency oscillation can be elicited in a hippocampal CA1 slice by
      the activation of metabotropic glutamate receptors with similar pharmacological
      and physiological profile that was found in vivo. We constructed a conductance
      based three-population network model of the hippocampal CA1 region to study the
      specific roles of neuron types in the generation of the in vitro theta
      oscillation and the emergent network properties. Interactions between pairs of
      neuron populations were studied systematically to assess synchronization and
      delay properties. We showed that the circuitry consisting of pyramidal cells and
      two types of hippocampal interneurons [basket and oriens lacunosum-moleculare (O
      LM) neurons] was able to generate coherent theta-frequency population
      oscillation. Furthermore, we found that hyperpolarization-activated nonspecific
      cation current in pyramidal cells, but not in O-LM neurons, plays an important
      role in the timing of spike generation, and thus synchronization of pyramidal
      cells. The model was shown to exhibit the same phase differences between neuron
      population activities found in vivo, supporting the idea that these patterns of
      activity are determined internal to the hippocampus.

PMID- 16899633
TI  - Control of the subthalamic innervation of the rat globus pallidus by D2/3 and D4
      dopamine receptors.
AB  - The effects of activating dopaminergic D(2/3) and D(4) receptors during
      activation of the subthalamic projection to the globus pallidus (GP) were
      explored in rat brain slices using the whole cell patch-clamp technique. Byocitin
      labeling and both orthodromic and antidromic activation demonstrated the
      integrity of some subthalamopallidal connections in in vitro parasagittal brain
      slices. Excitatory postsynaptic currents (EPSCs) that could be blocked by CNQX
      and AP5 were evoked onto pallidal neurons by local field stimulation of the
      subthalamopallidal pathway in the presence of bicuculline. Bath application of
      dopamine and quinpirole, a dopaminergic D(2)-class receptor agonist, reduced
      evoked EPSCs by about 35%. This effect was only partially blocked by sulpiride, a
      D(2/3) receptor antagonist. The sulpiride-sensitive reduction of the
      subthalamopallidal EPSC was associated with an increase in the paired-pulse ratio
      (PPR) and a reduction in the frequency but not the mean amplitude of spontaneous
      EPSCs (sEPSCs), indicative of a presynaptic site of action, which was confirmed
      by variance-mean analysis. The sulpiride-resistant EPSC reduction was mimicked by
      PD 168,077 and blocked by L-745,870, selective D(4) receptor agonist and
      antagonist, respectively, suggesting the involvement of D(4) receptors. The
      reduction of EPSCs produced by PD 168,077 was not accompanied by changes in PPR
      or the frequency of sEPSCs; however, it was accompanied by a reduction in mean
      sEPSC amplitude, indicative of a postsynaptic site of action. These results show
      that dopamine modulates subthalamopallidal excitation by presynaptic D(2/3) and
      postsynaptic D(4) receptors. The importance of this modulation is discussed.

PMID- 16899634
TI  - Intrinsic properties shape the firing pattern of ventral horn interneurons from
      the spinal cord of the adult turtle.
AB  - Interneurons in the ventral horn of the spinal cord play a central role in motor
      control. In adult vertebrates, their intrinsic properties are poorly described
      because of the lack of in vitro preparations from the spinal cord of mature
      mammals. Taking advantage of the high resistance to anoxia in the adult turtle,
      we used a slice preparation from the spinal cord. We used the whole cell blind
      patch-clamp technique to record from ventral horn interneurons. We characterized
      their firing patterns in response to depolarizing current pulses and found that
      all the interneurons fired repetitively. They displayed bursting, adapting,
      delayed, accelerating, or oscillating firing patterns. By combining
      electrophysiological and pharmacological tests, we showed that interneurons
      expressed slow inward rectification, plateau potential, voltage-sensitive
      transient outward rectification, and low-threshold spikes. These results
      demonstrate a diversity of intrinsic properties that may enable a rich repertoire
      of activity patterns in the network of ventral horn interneurons.

PMID- 16899635
TI  - Single neurons in the nucleus of the solitary tract respond selectively to bitter
      taste stimuli.
AB  - Molecular data suggest that receptors for all bitter ligands are coexpressed in
      the same taste receptor cells (TRCs), whereas physiological results indicate that
      individual TRCs respond to only a subset of bitter stimuli. It is also unclear to
      what extent bitter-responsive neurons are stimulated by nonbitter stimuli. To
      explore these issues, single neuron responses were recorded from the rat nucleus
      of the solitary tract (NST) during whole mouth stimulation with a variety of
      bitter compounds: 10 microM cycloheximide, 7 mM propylthiouracil, 10 mM
      denatonium benzoate, and 3 mM quinine hydrochloride at intensities matched for
      behavioral effectiveness. Stimuli representing the remaining putative taste
      qualities were also tested. Particular emphasis was given to activating taste
      receptors in the foliate papillae innervated by the quinine-sensitive
      glossopharyngeal nerve. This method revealed a novel population of bitter-best (B
      best) cells with foliate receptive fields and significant selectivity for bitter
      tastants. Across all neurons, multidimensional scaling depicted bitter stimuli as
      loosely clustered yet clearly distinct from nonbitter tastants. When neurons with
      posterior receptive fields were analyzed alone, bitter stimuli formed a tighter
      cluster. Nevertheless, responses to bitter stimuli were variable across B-best
      neurons, with cycloheximide the most, and quinine the least frequent optimal
      stimulus. These results indicate heterogeneity for the processing of ionic and
      nonionic bitter tastants, which is dependent on receptive field. Further, they
      suggest that neurons selective for bitter substances could contribute to taste
      coding.

PMID- 16899636
TI  - Differential regulation of two distinct voltage-dependent sodium currents by
      group III metabotropic glutamate receptor activation in insect pacemaker neurons.
AB  - Using whole cell patch-clamp technique and immunocytochemistry on adult dorsal
      unpaired median (DUM) neurons isolated from the cockroach Periplaneta americana
      CNS, we reported the characterization of a native mGluR, sharing pharmacological
      properties with vertebrate metabotropic glutamate receptor III (mGluRIII) that
      regulated voltage-dependent sodium current (I(Na)). The global I(Na) was
      dissociated by means of l-glutamate sensitivity, deactivation time constant,
      voltage dependence of activation and inactivation, recovery from inactivation,
      and intracellular regulation process. These two currents were respectively
      designated I(Na1) and I(Na2) for l-glutamate-sensitive and -insensitive sodium
      currents. l-glutamate selectively reduced I(Na1) by an increase of intracellular
      cAMP level. Using different activators and/or inhibitors of G proteins and
      cAMP/PKA cascade, together with St-Ht31 (an inhibitor of PKA binding to AKAP) and
      AKAP-79 antibodies, we established that mGluRIII was linked to I(Na1) by a Gi/o
      and a suspected Gs protein. According to the activated signaling pathway, l
      glutamate elevated the cAMP level, which thereby activated cytosolic PKA and
      released PKA bound to AKAP. As expected from both biophysical and pharmacological
      studies, we showed that, through an inhibition of I(Na1), l-glutamate increased
      DUM neuron spontaneous electrical activity. These results indicated that such
      mGluRIII-activated dual processes provided a new physiological control of
      pacemaker neuronal firing.

PMID- 16899637
TI  - Voltage-dependent sodium channels in spinal cord motor neurons display rapid
      recovery from fast inactivation in a mouse model of amyotrophic lateral
      sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized
      by a substantial loss of motor neurons in the spinal cord, brain stem, and motor
      cortex. Previous evidence showed that in a mouse model of a familial form of ALS
      expressing high levels of the human mutated protein Cu,Zn superoxide dismutase
      (Gly(93)-->Ala, G93A), the firing properties of single motor neurons are altered
      to induce neuronal hyperexcitability. To determine whether the functionality of
      the macroscopic voltage-dependent Na(+) currents is modified in G93A motor
      neurons, in the present work their physiological properties were examined. The
      voltage-dependent sodium channels were studied in dissociated motor neurons in
      culture from nontransgenic mice (Control), from transgenic mice expressing high
      levels of the human wild-type protein [superoxide dismutase 1 (SOD1)], and from
      G93A mice, using the whole cell configuration of the patch-clamp recording
      technique. The voltage dependency of activation and of steady-state inactivation,
      the kinetics of fast inactivation and slow inactivation of the voltage-dependent
      Na(+) channels were not modified in the mutated mice. Conversely, the recovery
      from fast inactivation was significantly faster in G93A motor neurons than that
      in Control and SOD1. The recovery from fast inactivation was still significantly
      faster in G93A motor neurons exposed for different times (3-48 h) and
      concentrations (5-500 microM) to edaravone, a free-radical scavenger.
      Clarification of the importance of these changes in membrane ion channel
      functionality may have diagnostic and therapeutic implications in the
      pathogenesis of ALS.

PMID- 16899639
TI  - Impedance modulation and feedback corrections in tracking targets of variable
      size and frequency.
AB  - Humans are able to adjust the accuracy of their movements to the demands posed by
      the task at hand. The variability in task execution caused by the inherent
      noisiness of the neuromuscular system can be tuned to task demands by both
      feedforward (e.g., impedance modulation) and feedback mechanisms. In this
      experiment, we studied both mechanisms, using mechanical perturbations to
      estimate stiffness and damping as indices of impedance modulation and submovement
      scaling as an index of feedback driven corrections. Eight subjects tracked three
      differently sized targets (0.0135, 0.0270, and 0.0405 rad) moving at three
      different frequencies (0.20, 0.25, and 0.33 Hz). Movement variability decreased
      with both decreasing target size and movement frequency, whereas stiffness and
      damping increased with decreasing target size, independent of movement frequency.
      These results are consistent with the theory that mechanical impedance acts as a
      filter of noisy neuromuscular signals but challenge stochastic theories of motor
      control that do not account for impedance modulation and only partially for
      feedback control. Submovements during unperturbed cycles were quantified in terms
      of their gain, i.e., the slope between their duration and amplitude in the speed
      profile. Submovement gain decreased with decreasing movement frequency and
      increasing target size. The results were interpreted to imply that submovement
      gain is related to observed tracking errors and that those tracking errors are
      expressed in units of target size. We conclude that impedance and submovement
      gain modulation contribute additively to tracking accuracy.

PMID- 16899638
TI  - Autocorrelation analysis of hair bundle structure in the utricle.
AB  - The ability of hair bundles to signal head movements and sounds depends
      significantly on their structure, but a quantitative picture of bundle structure
      has proved elusive. The problem is acute for vestibular organs because their hair
      bundles exhibit complex morphologies that vary with endorgan, hair cell type, and
      epithelial locus. Here we use autocorrelation analysis to quantify stereociliary
      arrays (the number, spacing, and distribution of stereocilia) on hair cells of
      the turtle utricle. Our first goal was to characterize zonal variation across the
      macula, from medial extrastriola, through striola, to lateral extrastriola. This
      is important because it may help explain zonal variation in response dynamics of
      utricular hair cells and afferents. We also use known differences in type I and
      II bundles to estimate array characteristics of these two hair cell types. Our
      second goal was to quantify variation in array orientation at single macular loci
      and use this to estimate directional tuning in utricular afferents. Our major
      findings are that, of the features measured, array width is the most distinctive
      feature of striolar bundles, and within the striola there are significant,
      negatively correlated gradients in stereocilia number and spacing that parallel
      gradients in bundle heights. Together with previous results on stereocilia number
      and bundle heights, our results support the hypothesis that striolar hair cells
      are specialized to signal high-frequency/acceleration head movements. Finally,
      there is substantial variation in bundle orientation at single macular loci that
      may help explain why utricular afferents respond to stimuli orthogonal to their
      preferred directions.

PMID- 16899640
TI  - Laser-evoked potentials are graded and somatotopically organized
      anteroposteriorly in the operculoinsular cortex of anesthetized monkeys.
AB  - The operculoinsular cortical region has a major role in the representation of
      noxious stimuli, based on functional imaging observations, clinical lesion
      studies, and EEG recordings of specifically pain-related laser-evoked potentials
      (LEPs) in humans. The source of LEPs has not been identified, and several somatic
      representations and cytoarchitectonic areas may be present in this complex
      region. To overcome the limitations of human studies, a primate model is needed
      in which the main LEP generator in this region can be localized and characterized
      using invasive methods. We obtained EEG recordings of evoked responses to noxious
      laser stimulation at different intensities and performed dipole source analyses
      in three anesthetized macaque monkeys. We show that LEPs can be recorded that 1)
      grade with stimulus intensity, 2) display two distinct responses corresponding to
      the "late" (Adelta-fiber) and the "ultralate" (C-fiber) LEPs recorded in humans,
      and 3) originate deep within the operculoinsular region, thus establishing a
      valid primate model for experimental analysis of LEPs. Further, we found that
      LEPs elicited from the leg, arm, and ear display a global somatotopy organized in
      the posteroanterior direction (leg posterior and arm and ear anterior), which
      contrasts starkly with the mediolateral (leg to face) gradient of the somatotopic
      representations in primary and secondary somatosensory cortices. These results
      provide evidence that the main generator of pain-related activity in
      operculoinsular cortex may participate in both the somatic localization and the
      intensity discrimination of pain sensations, and they indicate that it may be
      distinct from the traditional somatosensory cortices.

PMID- 16899641
TI  - Network architecture, receptive fields, and neuromodulation: computational and
      functional implications of cholinergic modulation in primary auditory cortex.
AB  - Two fundamental issues in auditory cortical processing are the relative
      importance of thalamocortical versus intracortical circuits in shaping response
      properties in primary auditory cortex (ACx), and how the effects of
      neuromodulators on these circuits affect dynamic changes in network and receptive
      field properties that enhance signal processing and adaptive behavior. To
      investigate these issues, we developed a computational model of layers III and IV
      (LIII/IV) of AI, constrained by anatomical and physiological data. We focus on
      how the local and global cortical architecture shape receptive fields (RFs) of
      cortical cells and on how different well-established cholinergic effects on the
      cortical network reshape frequency-tuning properties of cells in ACx. We identify
      key thalamocortical and intracortical circuits that strongly affect tuning curves
      of model cortical neurons and are also sensitive to cholinergic modulation. We
      then study how differential cholinergic modulation of network parameters change
      the tuning properties of our model cells and propose two different mechanisms:
      one intracortical (involving muscarinic receptors) and one thalamocortical
      (involving nicotinic receptors), which may be involved in rapid plasticity in
      ACx, as recently reported in a study by Fritz and coworkers.

PMID- 16899642
TI  - Responses of neurons in the ventral nucleus of the lateral lemniscus to
      sinusoidally amplitude modulated tones.
AB  - Fluctuations in the amplitude of a sound play an important role in our perception
      of pitch and acoustic space, but their neural analysis has not been fully
      elucidated. The ventral nucleus of the lateral lemniscus (VNLL) has been
      implicated in the processing of such temporal features of a sound. This study
      examines responses of neurons in the VNLL of unanesthetized rabbits to
      sinusoidally amplitude modulated tones, a type of stimulus that has often been
      used to investigate encoding of temporal information. Modulation transfer
      functions of responses were calculated in two ways: based on discharge rates
      (rMTFs) and on synchronization to the envelope (tMTFs). Among the variety of
      rMTFs, two types were readily identifiable: flat and band-pass. The responses of
      neurons exhibiting these types of rMTF differed in several ways. Neurons with
      flat rMTFs typically had moderate rates of spontaneous activity, sustained
      responses to short tone bursts, and low-pass or band-pass tMTFs. Neurons with
      band-pass rMTFs typically had low spontaneous activity, onset responses to short
      tone bursts, and flat tMTFs. The vast majority synchronized strongly to the
      modulation envelope. The best modulation frequencies of neurons with band-pass
      rMTFs extended from 14 to 283 Hz. The presence of neurons with band-pass rMTFs in
      the VNLL suggests that this nucleus plays a role in converting the temporal code
      for modulation frequency used in lower structures into a rate-based code for use
      higher in the auditory pathway. The substantial number of neurons with more
      complex modulation transfer functions indicates that the VNLL has other
      functions.

PMID- 16899643
TI  - An increase in calcium influx contributes to post-tetanic potentiation at the rat
      calyx of Held synapse.
AB  - We studied the contribution of a change in presynaptic calcium influx to
      posttetanic potentiation (PTP) in the calyx of Held synapse, an axosomatic
      synapse in the auditory brain stem. We made whole cell patch-clamp recordings of
      a principal cell after loading of the presynaptic terminal with a calcium dye.
      After induction of PTP by a high-frequency train of afferent stimuli, the Fluo-4
      fluorescence transients evoked by an action potential became on average 15 +/- 4%
      larger (n = 7). Model predictions did not match the fluorescence transients
      evoked by trains of brief calcium currents unless the endogenous calcium buffer
      had low affinity for calcium, making a contribution of saturation of the
      endogenous buffer to the synaptic potentiation we observed in the present
      experiments less likely. Our data therefore suggest that the increase of release
      probability during PTP at the calyx of Held synapse is largely explained by an
      increase in the calcium influx per action potential.

PMID- 16899644
TI  - Group delay of acoustic emissions in the ear.
AB  - It is commonly accepted that the cochlea emits sound by a backward traveling wave
      along the cochlear partition. This belief is mainly based on an observation that
      the group delay of the otoacoustic emission measured in the ear canal is twice as
      long as the forward delay. In this study, the otoacoustic emission was measured
      in the gerbil under anesthesia not only in the ear canal but also at the stapes,
      eliminating measurement errors arising from unknown external- and middle-ear
      delays. The emission group delay measured at the stapes was compared with the
      group delay of basilar membrane vibration at the putative emission-generation
      site, the forward delay. The results show that the total intracochlear delay of
      the emission is equal to or smaller than the forward delay. For emissions with an
      f2/f1 ratio <1.2, the data indicate that the reverse propagation of the emission
      from its generation site to the stapes is much faster than a forward traveling
      wave to the f2 location. In addition, that the round-trip delays are smaller than
      the forward delay implies a basal shift of the emission generation site, likely
      explained by the basal shift of primary-tone response peaks with increasing
      intensity. However, for emissions with an f1 << f2, the data cannot distinguish
      backward traveling waves from compression waves because of a very small f1 delay
      at the f2 site.

PMID- 16899646
TI  - A dogged pursuit of coincidence.

PMID- 16899645
TI  - Coherent spontaneous activity identifies a hippocampal-parietal memory network.
AB  - Despite traditional theories emphasizing parietal contributions to spatial
      attention and sensory-motor integration, functional MRI (fMRI) experiments in
      normal subjects suggest that specific regions within parietal cortex may also
      participate in episodic memory. Here we examined correlations in spontaneous
      blood-oxygenation-level-dependent (BOLD) signal fluctuations in a resting state
      to identify the network associated with the hippocampal formation (HF) and
      determine whether parietal regions were elements of that network. In the absence
      of task, stimuli, or explicit mnemonic demands, robust correlations were observed
      between activity in the HF and several parietal regions (including precuneus,
      posterior cingulate, retrosplenial cortex, and bilateral inferior parietal
      lobule). These HF-correlated regions in parietal cortex were spatially distinct
      from those correlated with the motion-sensitive MT+ complex. Reanalysis of event
      related fMRI studies of recognition memory showed that the regions spontaneously
      correlated with the HF (but not MT+) were also modulated during directed
      recollection. These regions showed greater activity to successfully recollected
      items as compared with other trial types. Together, these results associate
      specific regions of parietal cortex that are sensitive to successful recollection
      with the HF.

PMID- 16899647
TI  - Continuous tonic spike activity in spider warm cells in the absence of sensory
      input.
AB  - The warm cells of the spider tarsal organ respond very sensitively to low
      amplitude changes in temperature and discharge continuously as the rate of change
      in temperature reaches zero. To test whether the continuous tonic discharge
      remains without sensory input, we blocked the warm cell's receptive region by
      Epoxy glue. The activity continued in this situation, but its dependence on
      temperature changes was strongly reduced. We interpret this to mean that the warm
      cells exhibit specific intrinsic properties that underlie the generation of the
      tonic discharge. Experiments with electrical stimulation confirmed the
      observation that the warm cells persist in activity without an external drive. In
      warm cells with blocked receptive region, the response curves describing the
      relationship between the tonic discharge and the level of depolarization is the
      same for different temperatures. In warm cells with intact receptive region, the
      curves are shifted upward with rising temperature, as if the injected current is
      simply added to the receptor current. This indicates a modulating effect of the
      receptor current on the tonic discharge. Stimulation causes a change in the tonic
      discharge rate and thereby enables individual warm cells to signal the direction
      in addition to the magnitude of temperature changes.

PMID- 16899648
TI  - Characterization of myenteric sensory neurons in the mouse small intestine.
AB  - We recorded from myenteric AH/Dogiel type II cells, demonstrated mechanosensitive
      responses, and characterized their basic properties. Recordings were obtained
      using the mouse longitudinal muscle myenteric plexus preparation with patch-clamp
      and sharp intracellular electrodes. The neurons had an action potential hump and
      a slow afterhyperpolarization (AHP) current. The slow AHP was carried by
      intermediate conductance Ca2+ -dependent K+ -channel currents sensitive to
      charybdotoxin and clotrimazole. All possessed a hyperpolarization-activated
      current that was blocked by extracellular cesium. They also expressed a TTX
      resistant Na+ current with an onset near the resting potential. Pressing on the
      ganglion containing the patched neuron evoked depolarizing potentials in 17/18
      cells. The potentials persisted after synaptic transmission was blocked. Volleys
      of presynaptic electrical stimuli evoked slow excitatory postsynaptic potentials
      (EPSPs) in 9/11 sensory neurons, but 0/29 cells received fast EPSP input. The
      slow EPSP was generated by removal of a voltage-insensitive K+ current. Patch
      clamp recording with a KMeSO4-containing, but not a conventional KCl-rich,
      intracellular solution reproduced the single-spike slow AHPs and low input
      resistances seen with sharp intracellular recording. Cell-attached recording of
      intermediate conductance potassium channels supported the conclusion that the
      single-spike slow AHP is an intrinsic property of intestinal AH/sensory neurons.
      Unitary current recordings also suggested that the slow AHP current probably does
      not contribute significantly to the high resting background conductance seen in
      these cells. The characterization of mouse myenteric sensory neurons opens the
      way for the study of their roles in normal and pathological physiology.

PMID- 16899649
TI  - Decomposition of surface EMG signals.
AB  - This report describes an early version of a technique for decomposing surface
      electromyographic (sEMG) signals into the constituent motor unit (MU) action
      potential trains. A surface sensor array is used to collect four channels of
      differentially amplified EMG signals. The decomposition is achieved by a set of
      algorithms that uses a specially developed knowledge-based Artificial
      Intelligence framework. In the automatic mode the accuracy ranges from 75 to 91%.
      An Interactive Editor is used to increase the accuracy to > 97% in signal epochs
      of about 30-s duration. The accuracy was verified by comparing the firings of
      action potentials from the EMG signals detected simultaneously by the surface
      sensor array and by a needle sensor. We have decomposed up to six MU action
      potential trains from the sEMG signal detected from the orbicularis oculi,
      platysma, and tibialis anterior muscles. However, the yield is generally low,
      with typically < or = 5 MUs per contraction. Both the accuracy and the yield
      should increase as the algorithms are developed further. With this technique it
      is possible to investigate the behavior of MUs in muscles that are not easily
      studied by needle sensors. We found that the inverse relationship between the
      recruitment threshold and the firing rate previously reported for muscles
      innervated by spinal nerves is also present in the orbicularis oculi and the
      platysma, which are innervated by cranial nerves. However, these two muscles were
      found to have greater and more widespread values of firing rates than those of
      large limb muscles.

PMID- 16899650
TI  - Brief report: evaluating the Bedtime Pass Program for child resistance to bedtime
      -a randomized, controlled trial.
AB  - OBJECTIVE: To evaluate the Bedtime Pass Program (BPP), an extinction-based
      procedure for treating bedtime resistance in typically developing children.
      METHODS: A randomized, controlled trial in which nineteen 3- to 6-year-old
      children demonstrating bedtime resistance were randomly assigned to a Bedtime
      Pass or Monitoring Control group. The experimental condition involved parent
      monitoring plus the Bedtime Pass: a card exchangeable for one parental visit or
      excused departure from the room after bedtime, with parents ignoring subsequent
      bids for attention. RESULTS: Children in the Bedtime Pass condition left their
      rooms and called and cried out significantly less frequently than controls. They
      demonstrated significant reductions in the time required to quiet each night.
      Treatment effects were maintained at 3-month follow-up. Parents reported high
      levels of satisfaction and treatment acceptability. CONCLUSIONS: BPP is a
      noncomplex, socially acceptable, effective treatment for bedtime resistance. It
      retains the powerful effects of extinction-based procedures without the
      "extinction burst."

PMID- 16899651
TI  - Regulation and effects of modulation of telomerase reverse transcriptase
      expression in primordial germ cells during development.
AB  - Telomere length maintenance in the germ line from generation to generation is
      essential for the perpetuation of eukaryotic organisms. This task is performed by
      a specialized reverse transcriptase called telomerase. While this critical
      function of telomerase has been well established, the mechanisms that regulate
      telomerase in the germ line are still poorly understood. We now show, using a
      Pou5f1-GFP transgenic mouse model, that telomerase suppression in quiescent male
      primordial germ cells (PGCs) is accompanied by a decrease in expression of murine
      telomerase reverse transcriptase (TERT). To further assess the role of TERT in
      quiescent PGCs, we developed a chicken Actb gene promoter/cytomegalovirus
      enhancer (CAG)-Tert transgenic mouse strain that constitutively expresses murine
      TERT. Telomerase activity was detected in quiescent PGCs from CAG-Tert transgenic
      embryos, demonstrating that re-activation of TERT expression is sufficient to
      restore telomerase activity in these cells and implying that TERT expression is
      an important mechanism of telomerase regulation in PGCs. Fluorescence-activated
      cell-sorting (FACS) analysis of PGC frequency and cell cycle status revealed no
      effect of either overexpression or deficiency of TERT in CAG-Tert transgenic mice
      or Tert knock-out mice respectively. These results demonstrate that TERT per se
      does not affect proliferation or development of PGCs, in contrast with recent
      studies that suggest that TERT has a telomere-independent effect in certain stem
      cells. It is possible that the direct effect of TERT on cell behavior may be
      dependent on cell type.

PMID- 16899652
TI  - STAC: A method for testing the significance of DNA copy number aberrations across
      multiple array-CGH experiments.
AB  - Regions of gain and loss of genomic DNA occur in many cancers and can drive the
      genesis and progression of disease. These copy number aberrations (CNAs) can be
      detected at high resolution by using microarray-based techniques. However, robust
      statistical approaches are needed to identify nonrandom gains and losses across
      multiple experiments/samples. We have developed a method called Significance
      Testing for Aberrant Copy number (STAC) to address this need. STAC utilizes two
      complementary statistics in combination with a novel search strategy. The
      significance of both statistics is assessed, and P-values are assigned to each
      location on the genome by using a multiple testing corrected permutation
      approach. We validate our method by using two published cancer data sets. STAC
      identifies genomic alterations known to be of clinical and biological
      significance and provides statistical support for 85% of previously reported
      regions. Moreover, STAC identifies numerous additional regions of significant
      gain/loss in these data that warrant further investigation. The P-values provided
      by STAC can be used to prioritize regions for follow-up study in an unbiased
      fashion. We conclude that STAC is a powerful tool for identifying nonrandom
      genomic amplifications and deletions across multiple experiments. A Java version
      of STAC is freely available for download at http://cbil.upenn.edu/STAC.

PMID- 16899653
TI  - Predicting essential genes in fungal genomes.
AB  - Essential genes are required for an organism's viability, and the ability to
      identify these genes in pathogens is crucial to directed drug development.
      Predicting essential genes through computational methods is appealing because it
      circumvents expensive and difficult experimental screens. Most such prediction is
      based on homology mapping to experimentally verified essential genes in model
      organisms. We present here a different approach, one that relies exclusively on
      sequence features of a gene to estimate essentiality and offers a promising way
      to identify essential genes in unstudied or uncultured organisms. We identified
      14 characteristic sequence features potentially associated with essentiality,
      such as localization signals, codon adaptation, GC content, and overall
      hydrophobicity. Using the well-characterized baker's yeast Saccharomyces
      cerevisiae, we employed a simple Bayesian framework to measure the correlation of
      each of these features with essentiality. We then employed the 14 features to
      learn the parameters of a machine learning classifier capable of predicting
      essential genes. We trained our classifier on known essential genes in S.
      cerevisiae and applied it to the closely related and relatively unstudied yeast
      Saccharomyces mikatae. We assessed predictive success in two ways: First, we
      compared all of our predictions with those generated by homology mapping between
      these two species. Second, we verified a subset of our predictions with eight in
      vivo knockouts in S. mikatae, and we present here the first experimentally
      confirmed essential genes in this species.

PMID- 16899654
TI  - Hemizygous subtelomeres of an African trypanosome chromosome may account for over
      75% of chromosome length.
AB  - African trypanosomes are parasitic protozoa that infect a wide range of mammals,
      including humans. These parasites remain extracellular in the mammalian
      bloodstream, where antigenic variation allows them to survive the immune
      response. The Trypanosoma brucei nuclear genome sequence has been published
      recently. However, the significant chromosome size polymorphism observed among
      strains and subspecies of T. brucei, where total DNA content may vary up to 30%,
      necessitates a comparative study to determine the underlying basis and
      significance of such variation between parasites. In addition, the sequenced
      strain (Tb927) presents one of the smallest genomes analyzed among T. brucei
      isolates; therefore, establishing polymorphic regions will provide essential
      complementary information to the sequencing project. We have developed a Tb927
      high-resolution DNA microarray to study DNA content variation along chromosome I,
      one of the most size-variable chromosomes, in different strains and subspecies of
      T. brucei. Results show considerable copy number polymorphism, especially at
      subtelomeres, but are insufficient to explain the observed size difference.
      Additional sequencing reveals that >50% of a larger chromosome I consists of
      arrays of variant surface glycoprotein genes (VSGs), involved in avoidance of
      acquired immunity. In total, the subtelomeres appear to be three times larger
      than the diploid core. These results reveal that trypanosomes can utilize
      subtelomeres for amplification and divergence of gene families to such a
      remarkable extent that they may constitute most of a chromosome, and that the VSG
      repertoire may be even larger than reported to date. Further experimentation is
      required to determine if these results are applicable to all size-variable
      chromosomes.

PMID- 16899655
TI  - Graemlin: general and robust alignment of multiple large interaction networks.
AB  - The recent proliferation of protein interaction networks has motivated research
      into network alignment: the cross-species comparison of conserved functional
      modules. Previous studies have laid the foundations for such comparisons and
      demonstrated their power on a select set of sparse interaction networks.
      Recently, however, new computational techniques have produced hundreds of
      predicted interaction networks with interconnection densities that push existing
      alignment algorithms to their limits. To find conserved functional modules in
      these new networks, we have developed Graemlin, the first algorithm capable of
      scalable multiple network alignment. Graemlin's explicit model of functional
      evolution allows both the generalization of existing alignment scoring schemes
      and the location of conserved network topologies other than protein complexes and
      metabolic pathways. To assess Graemlin's performance, we have developed the first
      quantitative benchmarks for network alignment, which allow comparisons of
      algorithms in terms of their ability to recapitulate the KEGG database of
      conserved functional modules. We find that Graemlin achieves substantial
      scalability gains over previous methods while improving sensitivity.

PMID- 16899656
TI  - An approximately 140-kb deletion associated with feline spinal muscular atrophy
      implies an essential LIX1 function for motor neuron survival.
AB  - The leading genetic cause of infant mortality is spinal muscular atrophy (SMA), a
      clinically and genetically heterogeneous group of disorders. Previously we
      described a domestic cat model of autosomal recessive, juvenile-onset SMA similar
      to human SMA type III. Here we report results of a whole-genome scan for linkage
      in the feline SMA pedigree using recently developed species-specific and
      comparative mapping resources. We identified a novel SMA gene candidate, LIX1, in
      an approximately140-kb deletion on feline chromosome A1q in a region of conserved
      synteny to human chromosome 5q15. Though LIX1 function is unknown, the predicted
      secondary structure is compatible with a role in RNA metabolism. LIX1 expression
      is largely restricted to the central nervous system, primarily in spinal motor
      neurons, thus offering explanation of the tissue restriction of pathology in
      feline SMA. An exon sequence screen of 25 human SMA cases, not otherwise
      explicable by mutations at the SMN1 locus, failed to identify comparable LIX1
      mutations. Nonetheless, a LIX1-associated etiology in feline SMA implicates a
      previously undetected mechanism of motor neuron maintenance and mandates
      consideration of LIX1 as a candidate gene in human SMA when SMN1 mutations are
      not found.

PMID- 16899657
TI  - Human embryonic stem cells have a unique epigenetic signature.
AB  - Human embryonic stem (hES) cells originate during an embryonic period of active
      epigenetic remodeling. DNA methylation patterns are likely to be critical for
      their self-renewal and pluripotence. We compared the DNA methylation status of
      1536 CpG sites (from 371 genes) in 14 independently isolated hES cell lines with
      five other cell types: 24 cancer cell lines, four adult stem cell populations,
      four lymphoblastoid cell lines, five normal human tissues, and an embryonal
      carcinoma cell line. We found that the DNA methylation profile clearly
      distinguished the hES cells from all of the other cell types. A subset of 49 CpG
      sites from 40 genes contributed most to the differences among cell types. Another
      set of 25 sites from 23 genes distinguished hES cells from normal differentiated
      cells and can be used as biomarkers to monitor differentiation. Our results
      indicate that hES cells have a unique epigenetic signature that may contribute to
      their developmental potential.

PMID- 16899660
TI  - Enhanced nutty flavor formation in cheddar cheese made with a malty Lactococcus
      lactis adjunct culture.
AB  - Nutty flavor in Cheddar cheese is desirable, and recent research demonstrated
      that 2- and 3-methyl butanal and 2-methyl propanal were primary sources of nutty
      flavors in Cheddar. Because malty strains of Lac-tococcus lactis (formerly
      Streptococcus lactis var. malti-genes) are characterized by the efficient
      production of these and other Strecker aldehydes during growth, this study
      investigated the influence of a malty L. lactis adjunct culture on nutty flavor
      development in Cheddar cheese. Cheeses made with different adjunct levels (0,
      10(4) cfu/mL, and 10(5) cfu/mL) were ripened at 5 or 13 degrees C and analyzed
      after 1 wk, 4 mo, and 8 mo by a combination of instrumental and sensory methods
      to characterize nutty flavor development. Cheeses ripened at 13 degrees C
      developed aged flavors (brothy, sulfur, and nutty flavors) more rapidly than
      cheeses held at 5 degrees C. Additionally, cheeses made with the adjunct culture
      showed more rapid and more intense nutty flavor development than control cheeses.
      Cheeses that had higher intensities of nutty flavors also had a higher
      concentration of 2/3-methyl butanal and 2-methyl propanal compared with control
      cheeses, which again confirmed that these compounds are a source of nutty flavor
      in Cheddar cheese. Results from this study provide a simple methodology for
      cheese manufacturers to obtain consistent nutty flavor in Cheddar cheese.

PMID- 16899659
TI  - High-resolution genomic profiling of chromosomal aberrations using Infinium whole
      genome genotyping.
AB  - Array-CGH is a powerful tool for the detection of chromosomal aberrations. The
      introduction of high-density SNP genotyping technology to genomic profiling,
      termed SNP-CGH, represents a further advance, since simultaneous measurement of
      both signal intensity variations and changes in allelic composition makes it
      possible to detect both copy number changes and copy-neutral loss-of
      heterozygosity (LOH) events. We demonstrate the utility of SNP-CGH with two
      Infinium whole-genome genotyping BeadChips, assaying 109,000 and 317,000 SNP
      loci, to detect chromosomal aberrations in samples bearing constitutional
      aberrations as well tumor samples at sub-100 kb effective resolution. Detected
      aberrations include homozygous deletions, hemizygous deletions, copy-neutral LOH,
      duplications, and amplifications. The statistical ability to detect common
      aberrations was modeled by analysis of an X chromosome titration model system,
      and sensitivity was modeled by titration of gDNA from a tumor cell with that of
      its paired normal cell line. Analysis was facilitated by using a genome browser
      that plots log ratios of normalized intensities and allelic ratios along the
      chromosomes. We developed two modes of SNP-CGH analysis, a single sample and a
      paired sample mode. The single sample mode computes log intensity ratios and
      allelic ratios by referencing to canonical genotype clusters generated from
      approximately 120 reference samples, whereas the paired sample mode uses a paired
      normal reference sample from the same individual. Finally, the two analysis modes
      are compared and contrasted for their utility in analyzing different types of
      input gDNA: low input amounts, fragmented gDNA, and Phi29 whole-genome pre
      amplified DNA.

PMID- 16899658
TI  - Phylogenetic analyses of cyanobacterial genomes: quantification of horizontal
      gene transfer events.
AB  - Using 1128 protein-coding gene families from 11 completely sequenced
      cyanobacterial genomes, we attempt to quantify horizontal gene transfer events
      within cyanobacteria, as well as between cyanobacteria and other phyla. A novel
      method of detecting and enumerating potential horizontal gene transfer events
      within a group of organisms based on analyses of "embedded quartets" allows us to
      identify phylogenetic signal consistent with a plurality of gene families, as
      well as to delineate cases of conflict to the plurality signal, which include
      horizontally transferred genes. To infer horizontal gene transfer events between
      cyanobacteria and other phyla, we added homologs from 168 available genomes. We
      screened phylogenetic trees reconstructed for each of these extended gene
      families for highly supported monophyly of cyanobacteria (or lack of it).
      Cyanobacterial genomes reveal a complex evolutionary history, which cannot be
      represented by a single strictly bifurcating tree for all genes or even most
      genes, although a single completely resolved phylogeny was recovered from the
      quartets' plurality signals. We find more conflicts within cyanobacteria than
      between cyanobacteria and other phyla. We also find that genes from all
      functional categories are subject to transfer. However, in interphylum as
      compared to intraphylum transfers, the proportion of metabolic (operational) gene
      transfers increases, while the proportion of informational gene transfers
      decreases.

PMID- 16899661
TI  - Activity and nature of plasminogen activators associated with the casein micelle.
AB  - In fresh milk, plasminogen, the zymogen form of plasmin (PL), is the predominant
      form. Therefore, plasminogen activators (PA) can contribute significantly to PL
      activity in milk. Both tissue-type PA (tPA) and urokinase-type PA (uPA) exist in
      milk; however, contradictory findings have been reported for which type of PA is
      most closely associated with the casein micelles. Little is known about the
      factors that might lead to variations in the individual activities of the PA. The
      objective of this work was therefore to investigate possible factors that might
      affect the association of tPA and uPA with the casein micelle and their
      activities thereafter. Plasminogen activators were isolated from milk samples
      with different somatic cell counts following 2 different isolation protocols.
      Determination of uPA, tPA, and PL activities was carried out quantitatively
      following chromogenic assays using 2 different substrates, and qualitatively
      using specialized sodium dodecyl sulfate-PAGE. Different isolation methods and
      conditions led to differences in uPA, tPA, and PL activities. Urokinase-type PA
      activity was significantly higher in PA fractions isolated from milk with high
      somatic cell counts than from milk with low somatic cell counts. Activity results
      indicated that in pasteurized milk uPA could dissociate from the somatic cells
      and bind to casein. Moreover, a high level of PL in isolated PA fractions
      contributed to significantly enhanced PA activities. Overall, results confirmed
      the association of both uPA and tPA with the casein micelle; however, their
      amounts, activities, and molecular weights varied based on the nature of the milk
      and methods of separation, with uPA being the PA with greater potential to affect
      plasminogen activation in milk.

PMID- 16899662
TI  - Effect of protein composition on the cheese-making properties of milk from
      individual dairy cows.
AB  - The objective of this study was to evaluate the effect of variations in milk
      protein composition on milk clotting properties and cheese yield. Milk was
      collected from 134 dairy cows of Swedish Red and White, Swedish Holstein, and
      Danish Holstein-Friesian breed at 3 sampling occasions. Concentrations of alphaS1
      , beta-, and kappa-casein (CN), alpha-lactalbumin, and beta-lactoglobulin (LG) A
      and B were determined by reversed phase liquid chromatography. Cows of Swedish
      breeds were genotyped for genetic variants of beta- and kappa-CN. Model cheeses
      were produced from individual skimmed milk samples and the milk clotting
      properties were evaluated. More than 30% of the samples were poorly coagulating
      or noncoagulating, resulting in weak or no coagulum, respectively. Poorly and
      noncoagulating samples were associated with a low concentration of kappa-CN and a
      low proportion of kappa-CN in relation to total CN analyzed. Furthermore, the
      kappa-CN concentration was higher in milk from cows with the AB genotype than the
      AA genotype of kappa-CN. The concentrations of alphaS1-, beta-, and kappa-CN and
      of beta-LG B were found to be significant for the cheese yield, expressed as
      grams of cheese per one hundred grams of milk. The ratio of CN to total protein
      analyzed and the beta-LG B concentration positively affected cheese yield,
      expressed as grams of dry cheese solids per one hundred grams of milk protein,
      whereas beta-LG A had a negative effect. Cheese-making properties could be
      improved by selecting milk with high concentrations of alphaS1-, beta-, and kappa
      CN, with high kappa-CN in relation to total CN and milk that contains beta-LG B.

PMID- 16899663
TI  - Induction of interleukin-12 by Lactobacillus strains having a rigid cell wall
      resistant to intracellular digestion.
AB  - Some strains of lactobacilli can stimulate macrophages and dendritic cells to
      secrete IL-12, which plays a key role in activating innate immunity. We examined
      the IL-12-inducing ability of 47 Lactobacillus strains belonging to 10 species in
      mouse peritoneal macrophages, and characterized the properties important for the
      induction of IL-12. Although considerable differences in IL-12-inducing ability
      were observed among the strains tested, almost all strains belonging to the
      Lactobacillus casei group (L. casei, Lactobacillus rhamnosus, and Lactobacillus
      zeae) or to Lactobacillus fermentum induced high levels of IL-12. Phagocytosis of
      lactobacilli was necessary for IL-12 induction, and the strains with strong IL-12
      induction were relatively resistant to lysis in the macrophages. The sensitivity
      of Lactobacillus strains to in vitro treatment with M-1 enzyme, a member of the N
      acetylmuramidases, was negatively correlated with IL-12-inducing ability. Using a
      probiotic strain, L. casei strain Shirota (LcS), we showed that the cell wall of
      LcS could be digested by long-term treatment with a high dose of M-1 enzyme and
      that the IL-12-inducing ability was diminished according to the duration of the
      enzyme treatment. The soluble polysaccharide-peptidoglycan complex released from
      the cell wall of LcS did not induce IL-12, whereas the insoluble intact cell wall
      of LcS induced IL-12. These results suggest that the intact cell wall structure
      of lactobacilli is an important element in the ability to induce IL-12 and that
      Lactobacillus strains having a rigid cell wall resistant to intracellular
      digestion effectively stimulate macrophages to induce IL-12.

PMID- 16899664
TI  - Monitoring the chemical and textural changes during ripening of Iranian White
      cheese made with different concentrations of starter.
AB  - The effect of the concentration of starter inoculated to milk on the composition,
      free tyrosine-tryptophan content, microstructure, opacity, and fracture stress of
      Iranian White cheese (IWC) was studied during 50 d of ripening in brine. Three
      treatments of cheese were made using 1-fold (IWC1S), 2-fold (IWC2S), and 4-fold
      (IWC4S) concentrations of a direct-to-vat mesophilic mixed culture containing
      Lactococcus lactis ssp. cremoris and Lactococcus lactis ssp. lactis as starter.
      As ripening progressed, moisture and protein contents of the treatments
      continuously decreased, whereas their total ash, salt, and salt in moisture
      contents increased. Fat content and pH of cheeses remained stable during
      ripening. The pH of cheese milk at the time of renneting, which decreased by
      increasing the concentration of starter (6.57, 6.49, and 6.29 for IWC1S, IWC2S,
      and IWC4S, respectively), significantly affected most of the chemical
      characteristics and opacity of cheese. Lower pH values at renneting decreased
      moisture and ash contents, whereas cheese protein content increased. The
      concentration of free tyrosine-tryptophan in curd increased at first 29 d but
      decreased between d 29 and 49 of aging. The changes observed in cheese whiteness
      followed the changes in moisture content of the treatments. As the concentration
      of starter inoculated to milk increased, the value of fracture stress at a given
      ripening time significantly decreased, leading to a less resistant body against
      applied stress. A similar trend was also observed for fracture strain during
      cheese ripening. The micrographs taken by scanning electron microscopy provided a
      meaningful explanation for decrease in the value of fracture stress. As the
      cheese ripening progressed or the concentration of starter increased, the surface
      area occupied by the protein fraction in cheese microstructure decreased, leading
      the way to lower the force-bearing component in cheese texture.

PMID- 16899665
TI  - Identification and characterization of novel angiotensin-converting enzyme
      inhibitors obtained from goat milk.
AB  - The aim of the present study was to identify and characterize new inhibitory
      peptides of angiotensin I-converting enzyme (ACE) from goat milk and to analyze
      the effect of long-term intake of a goat milk hydrolysate-supplemented (GP-hyd)
      diet on the development of hypertension in spontaneously hypertensive rats (SHR).
      Three new inhibitory peptides for ACE (TGPIPN, SLPQ, and SQPK) were isolated. The
      inhibitory concentration 50% (IC50) values of individual peptides were 316, 330,
      and 354 micromol/L, respectively. Only TGPIPN was found to pass intact a
      monolayer of Caco-2 cells in small amounts. The SHR fed for 12 wk a diet (GP-hyd)
      enriched in a hydrolysate containing these peptides (estimated intake of TGPIPN
      was 230 mg/kg per d) showed lower (approximately 15 mmHg) systolic blood pressure
      than animals fed a control diet. The ACE activities in the aorta, left ventricle,
      and kidney were significantly decreased in the GP-hyd group compared with those
      of the control group and were similar to those found in SHR fed captopril (130
      mg/kg per d). Impaired endothelium-dependent relaxation to acetylcholine by
      aortic rings from SHR was improved in those fed the GP-hyd diet. The left
      ventricle weight and kidney weight index were significantly reduced in the GP-hyd
      group and captopril groups. Moreover, long-term treatment of SHR with a diet
      enriched in goat milk hydrolysate, or captopril, attenuated the development of
      hypertension, cardiac and renal hypertrophy, and endothelial dysfunction. These
      effects might be related to the in vivo inhibitory effects of the hydrolysate on
      tissue ACE activity.

PMID- 16899666
TI  - Bioactive peptides in ovine and caprine cheeselike systems prepared with
      proteases from Cynara cardunculus.
AB  - The potential angiotensin-converting enzyme (ACE)-inhibitory and antioxidant
      activities of peptides in water-soluble extracts, obtained from raw and
      sterilized ovine and caprine cheeselike systems coagulated with enzymes from the
      plant Cynara cardunculus, were assessed. Prior to the assay, the 3,000-Da
      permeate from 45-d-old cheeselike systems was fractionated by tandem
      chromatographic techniques. Several peaks were obtained in each chromatogram, but
      only some were associated with ACE-inhibitory or antioxidant activity or both.
      Peptides Tyr-Gln-Glu-Pro, Val-Pro-Lys-Val-Lys, and Tyr-Gln-Glu-Pro-Val-Leu-Gly
      Pro-* from beta-casein, as well as Arg-Pro-Lys and Arg-Pro-Lys-His-Pro-Ile-Lys
      His-* from alpha(s1)-casein exhibited ACE-inhibitory activity. Peptides released
      upon cleavage of the peptide bond Leu190-Tyr191 (either in ovine or caprine beta
      casein), and corresponding to the beta-casein sequence Tyr-Gln-Glu-Pro-*,
      possessed antioxidant activity.

PMID- 16899667
TI  - Discrimination of dairy industry isolates of the Lactobacillus casei group.
AB  - Lactobacilli are a major part of the microflora of the gut and of many fermented
      dairy products, and are found in a variety of environments. Lactobacillus casei,
      Lactobacillus paracasei, Lactobacillus rhamnosus, and Lactobacillus zeae form a
      closely related taxonomic group within the facultatively heterofermentative
      lactobacilli. The classification and nomenclature of these bacteria are
      controversial. In this study, relationships between these species were
      investigated using type strains and dairy industry isolates examined with DNA
      based techniques and conventional carbohydrate use tests. Carbohydrate use
      patterns gave poor discrimination of some species, but DNA PCR using specific
      primers targeted to sequences of the 16S rRNA gene discriminated 4 types
      consistent with the currently recognized species. Pulsed-field agarose gel
      electrophoresis of chromosomal NotI restriction fragments identified 18 different
      band patterns from 21 independent Lactobacillus isolates and confirmed the
      identity of L. casei strains from 2 culture collections (CSCC 5203 and ASCC 290),
      both representing the type strain of L. casei. Some isolates were reclassified as
      L. rhamnosus, suggesting that the prevalence of L. rhamnosus as a natural
      component of the microflora of dairy foods and dairy environments has previously
      been underestimated. These methods can provide a practical basis for
      discrimination of the species and identification of individual industrial
      strains.

PMID- 16899668
TI  - Antihypertensive effect of peptides obtained from Enterococcus faecalis-fermented
      milk in rats.
AB  - Previous studies have demonstrated that milk fermented with Enterococcus faecalis
      decreases the systolic blood pressure (SBP) and the diastolic blood pressure
      (DBP) of spontaneously hypertensive rats. In this study, we evaluated the
      antihypertensive activity of the following peptide sequences: LHLPLP, LHLPLPL,
      LVYPFPGPIPNSLPQNIPP, VLGPVRGPFP, and VRGPFPIIV. These peptides isolated from E.
      faecalis-fermented milk showed in vitro angiotensin I-converting enzyme
      inhibitory activity. Because the most potent angiotensin I-converting enzyme
      inhibitory sequences were LHLPLP and LVYPFPGPIPNSLPQ-NIPP, we administered
      different doses of these peptides to spontaneously hypertensive rats. High doses
      of the remaining sequences were also administered to these animals. Water served
      as a negative control and captopril as a positive control. All products were
      administered orally. The SBP and DBP were measured before administration and also
      at 2, 4, 6, 8, and 24 h after administration. Before administration of the
      different products, spontaneously hypertensive rats showed SBP and DBP values of
      218 +/- 2.5 and 157 +/- 5.9 mmHg, respectively (n = 30). The sequences LHLPLP,
      LVYPF-PGPIPNSLPQNIPP, VLGPVRGPFP, and VRGPFPIIV caused clear and significant
      decreases in SBP, DBP, or both in the animals. In particular, the
      antihypertensive effect could be clearly established when 2 or 3 mg/kg of LHLPLP
      was administered. These 2 doses of LHLPLP showed similar antihypertensive
      properties. Four hours after administration of captopril or the highest doses of
      the different peptides, the decreases in the SBP and the DBP (mmHg) were as
      follows: captopril (SBP = 52 +/- 5.8, DBP = 38.8 +/- 3.8), 3 mg/kg of LHLPLP (SBP
      = 25.3 +/- 8.2, DBP = 29.5 +/- 7.6), 6 mg/kg of LVYPFPGPIP-NSLPQNIPP (SBP = 14.9
      +/- 3.7, DBP = 8.7 +/- 4.4), 10 mg/kg of LHLPLPL (SBP = 7.7 +/- 4.1, DBP = 9.4 +/
      3.1), 10 mg/kg of VLGPVRGPFP (SBP = 16.2 +/- 5.8, DBP = 21.64 +/- 3.2), and 10
      mg/kg of VRGPFPIIV (SBP = 16.05 +/- 2.74, DBP = 9.19 +/- 3.49). The results
      obtained suggest that the sequences LHLPLP, LVYPFPGPIPNSLPQ-NIPP, VLGPVRGPFP, and
      VRGPFPIIV could be responsible, at least in part, for the antihypertensive
      properties described for E. faecalis-fermented milk.

PMID- 16899669
TI  - Pregnancy, bovine somatotropin, and dietary n-3 fatty acids in lactating dairy
      cows: I. Ovarian, conceptus, and growth hormone-insulin-like growth factor system
      responses.
AB  - The objective was to examine effects of bovine somatotropin (bST), pregnancy, and
      dietary fatty acids on reproductive responses in lactating dairy cows. Beginning
      at approximately 17 d in milk (DIM), a comparison was made of isoenergetic diets
      comprising supplementary lipids of whole cottonseed vs. calcium salts of fish oil
      enriched lipid (FO). Ovulation was synchronized in cows with a presynchronization
      plus Ovsynch protocol, and cows were inseminated artificially by appointment or
      not inseminated (d 0 = time of synchronized ovulation; 77 +/- 12 DIM). On d 0 and
      11, cows received bST (500 mg) or no bST. All cows were slaughtered on d 17.
      Number of cows in each group was as follows: control diet had 5 bST-treated
      cyclic (bST-C), 5 non-bST-treated cyclic (no bST-C), 4 bST-treated pregnant (bST
      P), and 5 non-bST-treated pregnant (no bST-P) cows; and cyclic cows fed FO diet
      had 4 bST-treated (bST-FO) and 5 non-bST-treated cyclic (no bST-FO-C) cows.
      Feeding FO increased milk production, number of class 1 follicles (2 to 5 mm),
      and decreased insulin during the period before d 0 compared with control-fed
      cows. The bST increased milk production, pregnancy rate [83% (5/6) vs. 40%
      (4/10)], conceptus length (45 vs. 34 cm), and interferon-tau in the uterine
      luminal flushings (9.4 vs. 5.3 microg) with no effect on interferon-tau mRNA
      concentration in the conceptus. Treatment with bST increased plasma growth
      hormone (GH) and insulin-like growth factor (IGF)-I. Among control-fed cows
      (cyclic and pregnant), bST decreased progesterone concentration in plasma. Cows
      fed FO had less plasma insulin than control-fed cyclic cows, and FO altered the
      plasma GH (bST-FO > bST-C) and IGF-I (bST-C > bST-FO-C) responses to bST
      injections. Endometrial IGF-I mRNA was reduced in pregnant cows and tended to
      decrease in those fed FO. The IGF-II mRNA was increased in the endometrium of
      pregnant and bST-treated cows fed the control diet. Cows fed FO had increased
      concentrations of IGF-II mRNA, when bST was not injected. The insulin-like growth
      factor binding protein-2 (IGFBP-2) mRNA was increased in bST-P cows, whereas bST
      decreased the IGFBP-2 mRNA in all cyclic cows. In summary, bST and FO seemed to
      modulate reproductive responses that may be beneficial to the developing
      conceptus and pregnancy rate.

PMID- 16899670
TI  - Pregnancy, bovine somatotropin, and dietary n-3 fatty acids in lactating dairy
      cows: II. Endometrial gene expression related to maintenance of pregnancy.
AB  - The objectives were to examine the effects of bovine somatotropin (bST),
      pregnancy, and dietary fatty acids on expression of key endometrial genes and
      proteins regulating prostaglandin synthesis in lactating dairy cows. Two diets
      were fed, at about 17 d in milk (DIM), in which oil of whole cottonseed (control
      diet) was compared with calcium salts of fish oil-enriched lipid (FO). Ovulation
      was synchronized in cows with a presynchronization plus Ovsynch protocol and cows
      were inseminated artificially or not inseminated on d 0 (d 0 = time of
      synchronized ovulation; 77 +/- 12 DIM). On d 0 and 11, cows received bST (500 mg)
      or no bST, and were slaughtered on d 17 to recover uterine secretions and
      endometrial tissue. Number of cows in the control diet: 5 bST-treated cyclic (bST
      C), 5 non-bST-treated cyclic (no bST-C), 4 bST-treated pregnant (bST-P), and 5
      non-bST-treated pregnant (no bST-P) cows and in the FO diet: 4 bST-treated FO
      cyclic (bST-FO-C) and 5 non-bST-treated cyclic (no bST-FO-C) cows. The FO diet
      increased progesterone receptor (PR) mRNA, and treatment with bST increased PR
      mRNA concentration in endometrium of no bST-C, but not in no bST-FO-C or no bST-P
      cows. Concentrations of estrogen receptor-alpha (ERalpha) mRNA and protein, and
      oxytocin receptor (OTR) mRNA were decreased in no bST-P cows compared with no bST
      C cows. Treatment with bST tended to increase OTR and ERalpha mRNA concentrations
      in cyclic cows fed control or FO diets. Immunohistochemistry demonstrated effects
      of bST, FO, and pregnancy on distributions of ERalpha and PR proteins in
      endometrium. Pregnancy and FO feeding decreased ERalpha abundance in luminal
      epithelium. Prostaglandin H synthase-2 (PGHS-2) protein was elevated in pregnant
      cows and localized to the luminal epithelium. Both FO and bST treatments reduced
      staining intensity of PGHS-2 protein. Concentrations of prostaglandin E synthase
      mRNA were elevated in either cyclic or pregnant cows in response to bST, whereas
      bST decreased prostaglandin F synthase mRNA in pregnant cows. Uterine lumen
      fluids had more PGF2alpha and prostaglandin E2 in pregnant than cyclic cows.
      Uterine lumen fluids of bST-P cows contained more prostaglandin E2 than those
      from no bST-P cows. In summary, both pregnancy and bST altered endometrial gene
      expression, and cyclic cows responded differently to bST than pregnant cows.
      Feeding FO modulated PR, ERalpha, and PGHS-2 expression and distribution among
      endometrial cell types in a manner that may favor establishment and maintenance
      of pregnancy.

PMID- 16899671
TI  - Pregnancy, bovine somatotropin, and dietary n-3 fatty acids in lactating dairy
      cows: III. Fatty acid distribution.
AB  - Our objective was to examine effects of exogenous bovine somatotropin (bST),
      pregnancy, and dietary fatty acids on fatty acid distribution in various tissues
      of lactating dairy cows. Two diets were fed, starting about 17 d in milk (DIM),
      in which oil of whole cottonseed (control diet) was compared with a calcium salt
      of fish oil-enriched lipid (FO; 1.9% of dietary DM). Starting at 44 +/- 5 DIM,
      ovulation was synchronized with a presynchronization plus Ovsynch protocol (d 0 =
      time of synchronized ovulation). Some cows were inseminated (77 +/- 12 DIM) to
      create a pregnant group. On d 0 and 11, cows received bST (500 mg) or no bST, and
      were killed on d 17 (94 +/- 12 DIM). Number of cows in control group was 5 bST
      treated cyclic (bST-C), 5 non-bST-treated cyclic (no bST-C), 4 bST-treated
      pregnant (bST-P), and 5 non-bST-treated pregnant (no bST-P) cows; and for the FO
      diet: 4 bST-treated (bST-FO-C) and 5 non-bST-treated cyclic (no bST-FO-C) cows.
      At slaughter, samples of endometrium, liver, muscle, s.c. adipose, internal
      adipose, and mammary gland were collected. Milk was collected at 75 +/- 5 DIM.
      Gas chromatography was used to determine fatty acid percentages in tissues and
      milk fat. Endometrium from the cows fed FO had increased proportions of C20:5 and
      C22:6, whereas C20:4 was decreased. Injections of bST reduced both C18:2 and the
      n-6:n-3 ratio, but increased C22:6 in endometrium of cyclic control-fed, but not
      pregnant cows. In addition, FO decreased the n-6:n-3 ratio in all tissues and
      milk fat except for s.c. and internal adipose tissue. Cows fed FO also had
      increased C18:3, C20:5, and C22:6 in the liver and mammary tissue, and C18:3 and
      C22:6 were increased in the milk fat. The FO diet decreased the Delta9-desaturase
      index [(product of Delta9-desaturase]/(product of Delta9-desaturase + substrate
      of Delta9-desaturase]; DIX) in muscle and s.c. tissues, accompanied by an
      increase in saturated fatty acid (SFA) percentage. In addition, FO diet decreased
      DIX in the endometrium. In mammary and internal adipose tissues, bST increased
      DIX in cyclic control-fed cows, whereas bST decreased DIX in FO-fed cows, with no
      difference in the concentration of SFA and UNSFA. Cis-9, trans-11 conjugated
      linoleic acid was increased in milk fat, but decreased in the muscle and s.c.
      adipose tissue of FO-fed cows. The FO-enriched lipid, bST treatment, and early
      pregnancy can alter fatty acid percentages and distributions that may alter
      tissue functionality and functional nutrients of consumer products.

PMID- 16899672
TI  - Characterization of bovine neutrophil gelatinase-associated lipocalin.
AB  - A protein of relative molecular mass of approximately 25,000 was purified from
      bovine colostrum by cation-exchange and size-exclusion chromatography. The N
      terminus of the protein matched the sequence predicted by the National Center for
      Biotechnology Information for the bovine homolog of human neutrophil gelatinase
      associated lipocalin, a glycoprotein of relative molecular mass 25,000 belonging
      to the family of lipocalins. The protein was further designated as bovine
      neutrophil gelatinase-associated lipocalin (bNGAL). Sodium dodecyl sulfate-PAGE
      of enzymically deglycosylated bNGAL indicated that the intact protein bears one N
      linked glycan. Monosaccharide and mass spectrometric analyses of released N
      linked carbohydrates revealed the presences of complex- and hybrid-type glycans,
      with galactose substituted with N-acetylgalactosamine. This substitution is
      typical for glycoproteins expressed in the bovine mammary gland. A specific ELISA
      revealed bNGAL concentrations in plasma and mature milk of about 0.05 and 1
      microg/mL, respectively, whereas values as high as 51 microg/mL were measured in
      colostrum. Thus, we have isolated and characterized a novel bovine (milk) protein
      that is a new member of the lipocalin family.

PMID- 16899673
TI  - Escherichia coli isolates' serotypes, genotypes, and virulence genes and clinical
      coliform mastitis severity.
AB  - Dairy cattle with clinical mastitis caused by Escherichia coli exhibit a wide
      range of disease severity, from mild, with only local inflammatory changes of the
      mammary gland, to severe, with significant systemic derangement. The present
      study was designed to examine the relationship between serotype and virulence
      genes of E. coli mastitis isolates, different levels of systemic disease
      severity, and farm from which the E. coli strain was obtained. One hundred twenty
      three E. coli milk isolates were obtained from cows with clinical mastitis of
      varying systemic disease severity from 6 different farms. No predominant serotype
      was identified by farm or by systemic disease severity; however, the most
      frequent serotype, O158:NM (n = 3), was isolated from cows in the moderate
      severity group. Virulence genes evaluated were identified infrequently and were
      not associated with systemic disease severity. Evaluation of genetic similarity
      showed no clustering assigned by farm or mastitis severity based on systemic
      disease signs. We concluded that a high degree of genotypic variability is
      characteristic of E. coli strains causing clinical mastitis within and between
      different farms and systemic severity groups, and that specific cow factors
      probably play a more important role in determining systemic disease severity.

PMID- 16899674
TI  - Optimizing ovulation to first GnRH improved outcomes to each hormonal injection
      of ovsynch in lactating dairy cows.
AB  - Ovulatory response to the first GnRH of Ovsynch is the critical determinant for
      successful synchronization of ovulation in dairy cows. Our objective in this
      study was to develop a pre-Ovsynch treatment that increased the percentage of
      cows that ovulated in response to the first GnRH injection of Ovsynch. To
      accomplish our goal, we evaluated a hormonal strategy that consisted of PGF2alpha
      and GnRH before the first GnRH of Ovsynch. Lactating dairy cows (n = 137) were
      assigned to receive either no treatment before Ovsynch (control) or 25 mg of
      PGF2alpha (PreP) followed 2 d later by 100 microg of GnRH (PreG), administered 4
      (G4G), 5 (G5G), or 6 (G6G) d before initiating the Ovsynch protocol. Transrectal
      ultrasonography was performed to assess follicular size and resulting ovulation,
      and blood samples were collected to measure circulating concentrations of
      progesterone and estradiol immediately before each hormonal injection. Cows were
      inseminated at a fixed time 16 h after final GnRH of Ovsynch. Pregnancy diagnosis
      was performed 35 d later by palpation per rectum of uterine contents. Proportion
      of cows that ovulated to first GnRH of Ovsynch was 56.0, 66.7, 84.6, and 53.8%
      for G4G, G5G, G6G, and controls, respectively, and was greater for G6G than for
      control cows. Luteolytic response to PGF2alpha of Ovsynch was greater in all
      treated than control cows (92.0, 91.7, 96.2, and 69.2% for G4G, G5G, G6G, and
      control, respectively). Synchronization rate to Ovsynch was greater (92 vs. 69%,
      respectively) in G6G than in control cows. In addition, cows that ovulated in
      response to first GnRH of Ovsynch had greater response to PGF2alpha of Ovsynch
      (92.7 vs. 77.1%, respectively) and greater synchronization rate to the overall
      protocol (87.9 vs. 62.9%, respectively) than those that did not ovulate.
      Concentrations of progesterone at PGF2alpha of Ovsynch, and estradiol and
      follicle size at final GnRH of Ovsynch, were identified as significant predictors
      of probability of pregnancy 35 d after artificial insemination. In summary, a
      PGF2alpha-and-GnRH based pre-Ovsynch strategy consisting of a 6-d interval
      between PreG and first GnRH of Ovsynch resulted in a greater ovulatory and
      luteolytic response to first GnRH and PGF2alpha of Ovsynch, respectively,
      compared with control cows. This, in turn, optimized synchronization rate to
      Ovsynch.

PMID- 16899675
TI  - Fecal shedding of Klebsiella pneumoniae by dairy cows.
AB  - Klebsiella pneumoniae is a common cause of clinical mastitis in dairy cattle.
      Wood products are considered to be the main source of Klebsiella on dairy farms.
      Environmental hygiene and use of inorganic bedding materials such as sand are
      recommended to control Klebsiella mastitis. However, Klebsiella mastitis still
      occurs on well-managed dairy farms that use sand as bedding material. In a 5-mo
      study in a New York State dairy herd performed during the summer of 2005, all of
      9 samples of unused sand bedding tested negative for Klebsiella, whereas 14 of 18
      samples of used sand bedding contained Klebsiella at a median level of 10(4.6)
      cfu/g. We hypothesized that fecal shedding of Klebsiella by dairy cows
      contributes to the presence of Klebsiella in the environment. Using a cheap and
      simple method based on ampicillin-containing MacConkey agar for screening, and
      biochemical tests for confirmation of species identity, 595 fecal samples from
      healthy dairy cattle were screened for presence of Klebsiella. In a longitudinal
      study of 100 cows followed over 5 mo, more than 80% of fecal samples tested
      positive for K. pneumoniae. The average prevalence of K. pneumoniae-positive
      fecal samples was also above 80% in a cross-sectional study of 100 cows from 10
      herds across New York and Massachusetts. Fecal shedding of K. pneumoniae by a
      large proportion of dairy cows may explain why Klebsiella mastitis occurs in
      herds that use inorganic bedding material or other bedding material that is free
      from Klebsiella upon introduction into the barn.

PMID- 16899676
TI  - Ceftiofur derivatives in serum, uterine tissues, cotyledons, and lochia after
      fetal membrane retention.
AB  - The objective of the study was to determine concentrations of ceftiofur
      derivatives after subcutaneous application of ceftiofur hydrochloride in cows
      with retained fetal membranes. Concentrations of ceftiofur derivatives detected
      as desfuroylceftiofuracetamide were determined in blood serum, endometrium,
      caruncles, cotyledons, and lochia during 72 h. After induction of parturition, 2
      primiparous and 4 multiparous cows having retained fetal membranes for at least
      12 h were studied. All cows received 3 consecutive injections (C1 to C3; 24 h
      apart) of 1-mg ceftiofur equivalents per kilogram of body weight as ceftiofur
      hydrochloride sterile suspension. Samples of blood, endometrium, caruncles,
      cotyledons, and lochia were collected immediately before each injection (0 h) and
      again at 4, 12, and 24 h after C1, C2, and C3. Blood samples were collected from
      coccygeal vessels. Caruncles were removed from the uterine lumen by manual
      extirpation and separated from cotyledons. Endometrial tissue (0.5 g) was
      collected by using Kenny's biopsy apparatus. For all samples, concentrations of
      potentially active ceftiofur derivatives were quantified using an HPLC assay.
      Within 2 h (serum), 4 h (endometrium), and 12 h (caruncles, cotyledons, lochia)
      after C1 and during the entire study period, mean concentration of ceftiofur
      derivatives exceeded the reported minimum drug concentrations required to inhibit
      the growth of 90% of isolates for relevant bacteria such as Escherichia coli,
      Fusobacterium necrophorum, and Arcanobacterium pyogenes. Only in single samples
      did concentrations decrease temporarily below the reported minimum drug
      concentrations required to inhibit the growth of 90% of isolates.

PMID- 16899677
TI  - Increasing milking intervals decreases the mammary blood flow and mammary uptake
      of nutrients in dairy cows.
AB  - Increasing the milking intervals reduces milk yield. The aims of this study were
      to determine whether the reduction in milk yield could be explained by a decrease
      in mammary uptake of the nutrients or a decrease in the efficiency of the mammary
      gland in using the milk precursors to synthesize milk components, or both. In a
      Latin square design with 5 periods, 4 multiparous lactating dairy cows in
      midlactation were milked at 8-, 12-, 16-, or 24-h intervals over a period of 7 d.
      The cows were surgically prepared to estimate the net mammary balance of nutrient
      precursors of milk components (glucose, alpha-amino nitrogen, acetate, beta
      hydroxybutyrate, and total glycerol). The efficiency of the mammary gland in
      synthesizing milk components was estimated by the mammary uptake:milk output
      ratio. After 7 d of treatment, the decrease in milk yield of 6.1 kg/d between 8-
      and 24-h milking intervals was associated with a reduction in the uptake of
      nutrients by the mammary gland, whereas the efficiency of the mammary gland in
      synthesizing milk components remained relatively unchanged. The mammary uptake
      decreased by 26% for glucose, 32% for alpha-amino nitrogen, 18% for acetate, 24%
      for total glycerol, and 24% for beta-hydroxybutyrate, respectively. These
      reductions in nutrient uptake were due to a decrease in the mammary blood flow
      (1.23 +/- 0.24 L/min). For milk fat precursors (acetate, beta-hydroxybutyrate,
      and total glycerol), the decrease in mammary blood flow explained the entire
      reduction in the mammary uptake. For glucose and the milk protein precursors, the
      reduction in the mammary blood flow explained 60% of the decrease in the mammary
      uptake, with the other 40% being accounted for by a reduction in the mammary
      extraction of nutrients. The nutrient uptake was altered as milk yield decreased.
      These decreases began with the 16-h milking interval and were higher at the 24-h
      milking interval.

PMID- 16899678
TI  - Milk cortisol concentration in automatic milking systems compared with auto
      tandem milking parlors.
AB  - Milk cortisol concentration was determined under routine management conditions on
      4 farms with an auto-tandem milking parlor and 8 farms with 1 of 2 automatic
      milking systems (AMS). One of the AMS was a partially forced (AMSp) system, and
      the other was a free cow traffic (AMSf) system. Milk samples were collected for
      all the cows on a given farm (20 to 54 cows) for at least 1 d. Behavioral
      observations were made during the milking process for a subset of 16 to 20 cows
      per farm. Milk cortisol concentration was evaluated by milking system, time of
      day, behavior during milking, daily milk yield, and somatic cell count using
      linear mixed-effects models. Milk cortisol did not differ between systems (AMSp:
      1.15 +/- 0.07; AMSf: 1.02 +/- 0.12; auto-tandem parlor: 1.01 +/- 0.16 nmol/L).
      Cortisol concentrations were lower in evening than in morning milkings (1.01 +/-
      0.12 vs. 1.24 +/- 0.13 nmol/L). The daily periodicity of cortisol concentration
      was characterized by an early morning peak and a late afternoon elevation in
      AMSp. A bimodal pattern was not evident in AMSf. Finally, milk cortisol decreased
      by a factor of 0.915 in milking parlors, by 0.998 in AMSp, and increased by a
      factor of 1.161 in AMSf for each unit of ln(somatic cell count/1,000). We
      conclude that milking cows in milking parlors or AMS does not result in relevant
      stress differences as measured by milk cortisol concentrations. The biological
      relevance of the difference regarding the daily periodicity of milk cortisol
      concentrations observed between the AMSp and AMSf needs further investigation.

PMID- 16899679
TI  - Mathematical model of the acute inflammatory response to Escherichia coli in
      intramammary challenge.
AB  - We constructed a mathematical model of the early response to Escherichia coli
      infection of the mammary gland and explored the roles and interactions between
      inflammatory cells and bacteria. The model incorporates 3 equations that describe
      the interactions among bacteria, milk somatic cells, and blood leukocyte
      densities. These 3 equations were fitted to cell densities observed during acute
      inflammatory responses in unvaccinated and vaccinated heifers inoculated with
      10(4) or 10(6) cfu of E. coli. The rates computed for the cellular transit from
      the storage sites to the blood and from the blood to the milk were lower in cows
      receiving 10(4) cfu but increased at approximately 6 x 10(-6) and 30 x 10(-6)
      microL/cfu per h in nonvaccinated or vaccinated cows inoculated with 10(6) cfu,
      respectively. The cellular rates of bacterial killing were highest in
      unvaccinated cows ( approximately 400 x 10(-6) microL/cell per h) when compared
      with vaccinated cows (200 to 300 x 10(-6) microL/cell per h). A critical density
      of milk somatic cells at which bacteria density is constant was computed from the
      model at 2 x 10(6) cells/mL, and a one-way sensitivity analysis revealed that the
      changes in milk cellular densities were mostly sensitive to variations in the
      rate of bacterial killing and in the rate of production of inflammatory cells.

PMID- 16899680
TI  - Evaluation of the Voluntary Johne's Disease Herd Status Program as a source of
      replacement cattle.
AB  - The objectives of this study were to evaluate the perceived value that enrolled
      producers gained from participation in the Voluntary Johne's Disease Herd Status
      Program (VJDHSP), and to evaluate the risk of infection with Mycobacterium avium
      ssp. paratuberculosis (MAP) of cattle reared in a presumed Johne's free
      environment vs. cattle raised in an environment of unknown Johne's status.
      Producers enrolled in level 3 or 4 of the VJDHSP (98 and 99% probability,
      respectively, of being free from MAP infection) were interviewed via telephone.
      Producers were asked questions pertaining to their participation in the VJDHSP,
      and asked to identify herds to which they had sold replacement heifers. These
      cattle were presumed to be uninfected before sale. Fifty-nine cattle (identified
      as having been purchased into infected herds as heifers) were identified as
      having been raised in uninfected herds and sold to producers with herds of
      unknown Johne's disease status. On the purchasing farm, fecal and blood samples
      were collected from each cow of VJDHSP origin and 3 randomly selected home-reared
      cows per VJDHSP cow matched by lactation as controls. Samples were tested using
      commercial ELISA (serum) and bacterial culture (feces). Results indicated that
      enrolled producers saw value in VJDHSP participation, and that cattle reared in
      VJDHSP herds were less likely to be infected with MAP than herdmates as measured
      by serum ELISA MAP antibody and by fecal culture. This study provides evidence of
      the value of the VJDHSP in providing economic value to participants and supports
      the promotion of VJDHSP herds as a source of replacement cattle of low infection
      risk for MAP.

PMID- 16899681
TI  - Short communication: genetic selection for milk production increases plasma
      ghrelin in dairy cows.
AB  - Ghrelin is an endogenous ligand of the growth hormone secretagogue receptor and a
      potent orexigenic agent in human and rodent studies, but there is limited
      information about its effect in dairy cows. Twelve low genetic merit and 9 high
      genetic merit Holstein-Friesian dairy cows in peak lactation that were offered
      unrestricted access to fresh pasture were used to determine whether genetic
      selection for milk production resulted in an associated increase in plasma
      ghrelin concentration in grazing dairy cows. Blood samples were taken prior to
      the a.m. milking (i.e., baseline) and following 2 h of grazing after the a.m.
      milking on 2 consecutive wk during peak lactation. Milk production and dry matter
      intake were greater in high genetic merit cows compared with low genetic merit
      cows. Plasma ghrelin and growth hormone concentrations were elevated in high
      genetic merit cows pre- and postgrazing, and there was no significant interaction
      between genetic merit and time of sampling. Genetic merit did not affect the
      plasma nonesterified fatty acid or glucose concentration, but the plasma
      concentrations of metabolites and hormones measured were diminished 2 h after
      feeding. Data indicate an increase in plasma ghrelin associated with genetic
      selection for milk production, and an associated increase in dry matter intake.

PMID- 16899682
TI  - Heat-treatment of bovine colostrum. II: effects of heating duration on pathogen
      viability and immunoglobulin G.
AB  - Batches (30-L) of first-milking bovine colostrum, inoculated with Mycoplasma
      bovis (10(8) cfu/mL), Listeria monocytogenes (10(6) cfu/mL), Escherichia coli
      O157:H7 (10(6) cfu/mL), Salmonella enteritidis (10(6) cfu/mL), and Mycobacterium
      avium subsp. paratuberculosis (Map; 10(3) cfu/mL), were heat-treated at 60
      degrees C for 120 min in a commercial on-farm batch pasteurizer system. Duplicate
      50-mL subsamples of colostrum were collected at 15-min intervals throughout the
      heat-treatment process for the purpose of bacterial culture and for measurement
      of IgG concentration (mg/mL) and antibody activity [log2(bovine viral diarrhea
      virus type 1 serum neutralization titer)]. Four replicate batches of colostrum
      were run for each of the 5 pathogens studied. There was no effect of heating
      moderate- to high-quality colostrum at 60 degrees C for at least 120 min on mean
      IgG concentration (pre = 60.5 mg/mL; post = 59.1 mg/mL). Similarly, there was no
      effect of heat-treatment on the mean log2 bovine viral diarrhea virus type 1
      serum neutralization titer (pre = 12.3; post = 12.0). Viable M. bovis, L.
      monocytogenes, E. coli O157:H7, and S. enteritidis added to colostrum could not
      be detected after the colostrum was heat-treated at 60 degrees C for 30 min.
      Average bacteria counts showed that Map was not detected when batches were heated
      at 60 degrees C for 60 min. Although the authors believe that heat-treating
      colostrum at 60 degrees C for 60 min should be sufficient to eliminate Map from
      colostrum in most situations, further research is needed to determine whether
      these findings may be replicated, given that variability was observed in Map
      culture results.

PMID- 16899683
TI  - Changes in Llama (Lama glama) milk composition during lactation.
AB  - Milk samples were collected weekly from 10 llamas during the first 27 wk after
      parturition under controlled stable conditions. Mean values for the
      concentrations of the major milk components across the lactation period were
      4.70% fat, 4.23% protein, 5.93% lactose, 15.61% dry matter, and 22.62 mg/dL of
      milk urea N. All constituents were affected by the stage of lactation. There was
      an increase in fat to protein ratio as protein concentration declined and fat
      concentration increased. Fat, protein, and lactose concentrations changed during
      the transition from colostrum to milk. In the first month postpartum, fat
      concentration remained constant, protein decreased, and lactose increased.
      Starting with wk 5 postpartum, fat and protein increased and lactose decreased
      until the end of lactation. Among the major constituents fat had the highest
      variation. The mean gross energy concentration of milk was 3.88 kJ/g and showed a
      similar course as protein. Fat contributed 48.0%, protein 26.3%, and lactose
      25.7% to the gross energy in the milk. Milk urea N values were higher than those
      found in ruminants and increased with stage of lactation, whereas the pH
      decreased. The analyzed milk components were not affected by the lactation number
      of the animal, except milk urea N. Somatic cell counts indicated the absence of
      mastitis and revealed that the average somatic cell count of uninfected llamas is
      lower than in animals usually used for milk production. The 2 algebraic models
      fitted by a nonlinear regression procedure to the data resulted in suitable
      prediction curves for the constituents (R2 = 0.76 to 0.94). The courses of major
      milk constituents in llamas during lactation are similar to those in domesticated
      ruminants, although different in their values. The established curves facilitate
      the composition of milk replacers at different stages of lactation for nursing
      llamas whose dams died or are agalactic.

PMID- 16899684
TI  - Effects of perennial ryegrass cultivars on milk yield and nitrogen utilization in
      grazing dairy cows.
AB  - The effects of 4 diploid perennial ryegrass cultivars that differed in water
      soluble carbohydrate (WSC) concentrations on milk yield and nitrogen (N)
      utilization in dairy cows were evaluated in a 2-yr grazing experiment. Twelve
      lactating dairy cows were assigned to 1 cultivar for a 2-wk period in a 4 x 4
      Latin square design with 3 replicates. Each year, the experiment lasted 8 wk.
      Swards were in a vegetative stage throughout the experiment. Herbage constituents
      were determined, and DM intake was estimated with the n-alkane technique.
      Nitrogen utilization was calculated as N excreted in milk divided by N intake,
      assuming a zero N retention. Two cultivars had consistently higher WSC
      concentrations and slightly lower neutral detergent fiber concentrations than the
      other 2 cultivars. The ranking of the cultivars in chemical composition traits in
      both years was rather consistent. Cows grazing the cultivar with the lowest
      concentration of WSC had the lowest herbage DM intake, N intake, milk yield, and
      milk N yield in 2002, but with a similar difference in WSC concentration, no
      differences among cultivars were found in 2003. In both years, milk urea N
      concentration was slightly higher for cows grazing the cultivar with the lowest
      WSC concentration, although it was significant only in 2003. Nitrogen utilization
      (N milk:N intake, g/g) varied between 0.241 and 0.246 in 2002 and between 0.190
      and 0.209 in 2003, and in both years there was no effect of cultivar. At
      relatively high N concentrations in grass and only small differences among
      cultivars in neutral detergent fiber concentrations, cultivars with an elevated
      WSC concentration did not increase N utilization in grazing dairy cows.

PMID- 16899685
TI  - Short communication: effectiveness of sample duplication to control error in
      ruminant digestion studies.
AB  - Eight ruminally cannulated lactating dairy cows from a study on the effect of
      dietary rumen-degraded protein on production and digestion of nutrients were used
      to assess using sample duplication to control day-to-day variation within animals
      and errors associated with sampling and laboratory analyses. Two consecutive
      pooled omasal samples, each representing a feeding cycle, were obtained from each
      cow in each period. The effectiveness of sample duplication in error control was
      tested by comparing the variance of the difference in treatment means when taking
      2 samples from each cow in each period to the variance when taking only one
      sample. Compared with no duplication, sample duplication improved precision by
      reducing variance by 50, 40, 31, 23, 23, and 9% for, respectively, rumen
      undegraded protein flows, ruminal neutral detergent fiber digestibility,
      microbial nonammonia N flow, microbial efficiency, organic matter flow, and
      organic matter truly digested in the rumen. For these same variables, reductions
      in the standard errors of the difference between treatment means due to sample
      duplication represented 100, 87, 73, 59, 58, and 27% of the predicted reductions
      resulting from doubling the number of experimental units without sample
      duplication. Sample duplication can substantially reduce experimental error
      originating from day-to-day variation within cows, sample collection, and
      laboratory analyses, thus improving statistical power in ruminant digestion
      studies.

PMID- 16899686
TI  - Short communication: effect of number of extractions on percentage of long-chain
      fatty acids from fresh alfalfa.
AB  - Accurate determination of fatty acids in fresh forage is very important when
      studying biohydrogenation. Fatty acids from fresh alfalfa were extracted by
      hexane:isopropanol (H:IP, 3:2 vol/vol) in 3 sequential extractions. The
      percentage and profile of fatty acids from each of the 3 extractions were
      evaluated by a randomized complete block design with repeated measures in space.
      Samples of fresh alfalfa were randomly harvested and immediately submerged in
      liquid nitrogen. For the first extraction, approximately 5 g of the frozen
      alfalfa was mixed with 18 mL of H:IP per gram of material. Samples were then
      centrifuged and the supernatant was collected. The second and third extractions
      were done by adding H:IP to the pellet (3 mL/g of the original sample weight),
      mixing for 2 min, and then centrifuging. Samples were submerged in H:IP and
      stored in the dark at 8 degrees C at all times. The solvent from each extraction
      was partially evaporated and the fatty acids methylated by methanolic HCl.
      Repeated extractions increased the percentage of total fatty acids recovered from
      the samples. The concentration of fatty acids in the alfalfa after 3 extractions
      was 4.0%. The first, second, and third extractions resulted in 92.7, 4.8, and
      2.6% of the total fatty acids extracted, respectively. There was no effect of
      extraction on the proportion of 16:0, 18:0, 18:1, and 18:2 fatty acids. However,
      the proportion of 18:3 in the extract decreased from the first to the second
      extraction and the ratio of saturated to unsaturated fatty acid increased from
      the first to the second extraction. The results of this experiment revealed that
      the profile of fatty acids can vary with the number of extractions performed. The
      higher amount of 18:3 in the first extraction may reflect the higher proportion
      of linolenic acid in the more easily extracted plant fractions.

PMID- 16899687
TI  - Absorption and digestive tract metabolism of 2-hydroxy-4-methylthiobutanoic acid
      in lambs.
AB  - Anabolic availability of the hydroxyl methionine analog, 2-hydroxy-4
      methylthiobutanoic acid (HMTBA), given as oral doses to lambs, was quantified
      both directly as appearance in the portal vein and as synthesis to Met by
      digestive tract tissues. Eight lambs, prepared with vascular catheters in the
      mesenteric and portal veins plus the aorta, received twice daily for 7 d either
      0.46 g or 2 g of HMTBA. On d 7, [1-13C]HMTBA was supplied as 1 oral dose while
      [methyl-2H3]Met was infused into the jugular vein. Peak absorption as HMTBA
      occurred 70 to 90 min after the oral dose. All digestive tract tissues converted
      HMTBA to Met, equivalent to 24% of the Met provided by the diet for the larger
      HMTBA dose. Overall, total availability of HMBTA averaged 17.9% of the dose
      (range 10.6 to 27.9%), with 12.5% (range 7 to 22%) as absorbed HMBTA and the
      remainder as Met synthesized by digestive tract tissues. Release of 13CO2 into
      the portal vein accounted for another 23% of the dose. In all digestive tract
      tissues, the d-isomer was present in a smaller proportion than in the dose. In
      terms of whole-body kinetics, HMTBA loss from the plasma followed first-order
      kinetics, with a mean biological half-life of 76 min. Using this value, a simple
      model was devised to estimate HMTBA absorption based on peripheral plasma
      samples. When compared with direct measures of absorption, the model gave a slope
      of 0.81 (R2 = 0.68) and offers a practical means to test HMTBA availability to
      animals.

PMID- 16899688
TI  - Feed stalls affect the social and feeding behavior of lactating dairy cows.
AB  - The first objective of this study was to study the effects of increased bunk
      space on the frequency of aggressive behavior at the feed bunk and on feed
      access. The second objective was to determine whether the addition of partitions
      (feed stalls) between adjacent cows would provide additional protection while
      feeding, particularly for subordinate cows. Twenty-four lactating Holstein cows
      were subjected to each of 3 treatments in 3 successive 10-d treatment periods
      using a 3 x 3 Latin square design. The treatments tested were: 1) 0.64 m of feed
      bunk space/cow, 2) 0.92 m of feed bunk space/cow, and 3) feed stalls (0.87 m of
      feed bunk space/cow with feed stall partitions separating adjacent cows). Time
      lapse video was used to quantify the feeding and standing behavior, as well as
      the aggressive behavior (displacements) displayed by the cows at the feed bunk.
      To meet our first and second objectives, we compared data from the 0.64 m/cow
      treatment with that from the 0.92 m/cow treatment, and data from the 0.92 m/cow
      treatment with that from the feed-stall treatment, respectively. Total daily
      feeding time increased when feed bunk space was increased from 0.64 to 0.92
      m/cow. Further, the time spent standing in the feeding area while not feeding and
      the frequency of aggressive interactions at the feed bunk decreased when more
      bunk space was provided. The addition of feed stalls resulted in more pronounced
      effects compared with when cows had 0.92 m/cow of bunk space. The feed stalls
      also forced cows to change the strategy by which they displaced others from the
      feed bunk, forcing them to also initiate contact at the rear of the animal they
      were displacing rather than only from the front and side, as in the other 2
      treatments. Further, when the cows were provided with additional feeding space,
      particularly when combined with feed stalls, those cows with lower social status
      at the feed bunk experienced the greatest decreases in the number of times they
      were displaced per day. The results indicated that providing increased feed bunk
      space, particularly when combined with feed stalls, will improve access to the
      feed and reduce competition at the feed bunk, particularly for subordinate cows.

PMID- 16899689
TI  - Holstein-Friesian strain and feed effects on milk production, body weight, and
      body condition score profiles in grazing dairy cows.
AB  - Data from 113 lactations across 76 cows between the years 2002 to 2004 were used
      to determine the effect of strain of Holstein-Friesian (HF) dairy cow and
      concentrate supplementation on milk production, body weight (BW), and body
      condition score (BCS; 1 to 5 scale) lactation profiles. New Zealand (NZ) and
      North American (NA) HF cows were randomly allocated to 1 of 3 levels of
      concentrate supplementation [0, 3, or 6 kg of dry matter (DM)/cow per d] on a
      basal pasture diet. The Wilmink exponential model was fitted within lactation
      (Y(DIM) = a + b e(-0.05 x DIM) + c x DIM). The median variation explained by the
      function for milk yield was 86%, between 62 and 69% for milk composition, and 80
      and 70% for BW and BCS, respectively. North American cows and cows supplemented
      with concentrates had greater peak and 270-d milk yield. Concentrate
      supplementation tended to accelerate the rate of incline to peak milk yield, but
      persistency of lactation was not affected by either strain of HF or concentrate
      supplementation. No significant strain by diet interaction was found for
      parameters reported. New Zealand cows reached nadir BCS 14 d earlier and lost
      less BW (22 kg) postcalving than NA cows. Concentrate supplementation reduced the
      postpartum interval to nadir BW and BCS, and incrementally increased nadir BCS.
      New Zealand cows gained significantly more BCS (i.e., 0.9 x 10(-3) units/d more)
      postnadir than NA cows, and the rate of BCS replenishment increased linearly with
      concentrate supplementation from 0.5 x 10(-3) at 0 kg of DM/d to 0.8 x 10(-3) and
      1.6 x 10(-3) units/d at 3 and 6 kg of DM/d concentrates, respectively. Although
      there was no significant strain by diet interaction for parameters reported,
      there was a tendency for a strain by diet interaction in 270-d BCS, suggesting
      that the effect of concentrate supplementation on BCS gain was, at least partly,
      strain dependent.

PMID- 16899691
TI  - Effects of dairy cow diet forage proportion on duodenal nutrient supply and
      urinary purine derivative excretion.
AB  - Four mature Holstein-Friesian dairy cows were used in a 4 x 4 Latin square change
      over design experiment made up of four 4-wk periods to investigate the
      relationship between microbial protein flow to the duodenum and excretion of
      purine derivatives (PD) in the urine. Four dietary treatments based on ad libitum
      access to ryegrass silage were offered, with a standard dairy concentrate
      included at different forage:concentrate (F:C) ratios, calculated on a dry matter
      basis: 80:20, 65:35, 50:50, and 35:65. Feed intakes increased as the proportion
      of concentrate in the diet increased, despite a concurrent decrease in silage
      intake. Increased feed intake led to increased nutrient flow to the duodenum.
      Milk yields increased as the diet F:C ratio decreased, with cows offered the
      35:65 diet yielding nearly 8 kg/d more milk than cows offered the 80:20 diet; the
      concentrations of milk fat decreased and milk protein increased with a decreasing
      F:C ratio. Purine derivative excretion in the urine increased with an increasing
      proportion of concentrate in the diet, and there was a strong linear relationship
      between total PD excretion (allantoin and uric acid) and microbial N flow to the
      duodenum: microbial N (g/d) = 19.9 + 0.689 x total PD (mmol/d); R = 0.887. This
      strengthens the case for using PD excretion as a noninvasive marker of microbial
      protein flow from the rumen in dairy cows.

PMID- 16899690
TI  - Selenium supplementation of lactating dairy cows: effect on selenium
      concentration in blood, milk, urine, and feces.
AB  - The objectives were to determine effects of graded levels of selenized yeast
      derived from a specific strain of Saccharomyces cerevisiae (CNCM I-3060) on
      animal performance and in selenium concentrations in the blood, milk, feces, and
      urine of dairy cows compared with sodium selenite; and to provide preliminary
      data on the proportion of selenium as selenomethionine in the milk and blood.
      Twenty Holstein cows were used in a 5 x 5 Latin square design study in which all
      cows received the same total mixed rations, which varied only in source or
      concentration of dietary selenium. There were 5 experimental treatments. Total
      dietary selenium of treatment 1, which received no added selenium, was 0.15 mg/kg
      of dry matter, whereas values for treatments 2, 3, and 4, derived from selenized
      yeast, were 0.27, 0.33, and 0.40 mg/kg of dry matter, respectively. Treatment 5
      contained 0.25 mg of selenium obtained from sodium selenite/kg of dry matter.
      There were no significant treatment effects on animal performance, and blood
      chemistry and hematology showed few treatment effects. Regression analysis noted
      significant positive linear effects of increasing dietary selenium derived from
      selenized yeast on selenium concentrations in the milk, blood, urine, and feces.
      In addition, milk selenium results indicated improved bioavailability of selenium
      from selenized yeast, compared with sodium selenite. Preliminary analyses showed
      that compared with sodium selenite, the use of selenized yeast increased the
      concentration of selenomethionine in the milk and blood. There was no indication
      of adverse effects on cow health associated with the use of selenized yeast.

PMID- 16899693
TI  - Effects of feeding frequency and feeding level on nutrient utilization in heavy
      preruminant calves.
AB  - The objective of this study was to determine the effects of feeding frequency
      (FF) and feeding level (FL) on protein and energy metabolism in adapted, heavy
      preruminant calves. It was hypothesized that an increased FF would increase
      protein utilization by an improved synchrony between the supply of and
      requirements for protein during the day when a quickly hydrolyzable protein
      source was used. Eighteen Holstein Friesian calves of 136 +/- 3 kg of body weight
      were assigned to FF (1, 2, or 4 meals daily) at 2 FL (1.5 or 2.5 times the
      metabolizable energy requirements for maintenance), except for calves fed once
      daily (only at a low FL). Calves were individually housed in respiration chambers
      during 2 experimental periods of 10 d. Whey protein was the only protein source
      in the diet. Neither FL nor FF affected apparent fecal nutrient digestibility.
      Increasing FF increased the efficiency with which digestible protein was utilized
      in calves. The increase was greater at a high FL (+11% from 2 to 4 meals/d) than
      at a low FL (+5% from 2 to 4 meals/d), but no significant interaction occurred
      between FL and FF. An increased FF and a higher FL enhanced fat deposition. Heat
      production was not affected by FF, but its circadian rhythm differed considerably
      between FF. Activity-related heat production was not affected by FF or FL. Thus,
      increasing FF improved the efficiency with which protein and energy were utilized
      in heavy preruminant calves when a quickly hydrolyzable protein source was used.

PMID- 16899692
TI  - Diets during far-off and close-up dry periods affect periparturient metabolism
      and lactation in multiparous cows.
AB  - The objectives of this study were to determine the effects of far-off and close
      up diets on prepartum metabolism, postpartum metabolism, and postpartum
      performance of multiparous Holstein cows. From dry-off to -25 d relative to
      expected parturition (far-off dry period), cows were fed a control diet to meet
      National Research Council (NRC) recommendations for net energy for lactation
      (NE(L)) at ad libitum intake (100NRC; n = 25) or a higher nutrient density diet,
      which was fed for either ad libitum intake to provide at least 150% of calculated
      NE(L) requirement (150NRC; n = 25) or at restricted intake to provide 80% of
      calculated NE(L) requirements (80NRC; n = 24). From -24 d relative to expected
      parturition until parturition (close-up period), cows were fed a diet that met or
      exceeded NRC nutrient recommendations at either ad libitum intake (n = 38) or
      restricted intake (n = 36) to provide 80% of the calculated NE(L) requirement.
      After parturition, all cows were fed a lactation diet and measurements were made
      through 56 d in milk (DIM). Prepartum metabolism was consistent with the plane of
      nutrition. During the first 10 DIM, far-off treatments had significant carryover
      effects on dry matter intake, energy balance, serum nonesterified fatty acid
      (NEFA) concentration, and serum beta-hydroxybutyrate concentration. Cows with the
      lower energy balance during the far-off period (100NRC and 80NRC) had higher dry
      matter intake and energy balance and lower serum NEFA and beta-hydroxybutyrate
      during the first 10 DIM. There were no effects of close-up diet and no
      interactions of far-off and close-up treatments. During the first 56 DIM, there
      were no residual effects of far-off or close-up diets on dry matter intake, milk
      yield or composition, body weight, body condition score, serum glucose and
      insulin concentrations, or muscle lipid concentration. Serum NEFA was higher for
      150NRC than 80NRC; 100NRC was intermediate. Thus, the effects of far-off and
      close-up treatments on postpartum variables diminished as lactation progressed.
      Overfeeding during the far-off period had a greater negative impact on peripartum
      metabolism than did differences in close-up period nutrition.

PMID- 16899696
TI  - Analysis of the relationship between somatic cell score and functional longevity
      in Canadian dairy cattle.
AB  - The aim of this study was to assess the level of somatic cell count (SCC) and to
      explore the impact of somatic cell score (SCS) on the functional longevity of
      Canadian dairy cattle by using a Weibull proportional hazards model. Data
      consisted of 1,911,428 cows from 15,970 herds sired by 7,826 sires for Holsteins,
      80,977 cows in 2,036 herds from 1,153 sires for Ayrshires, and 53,114 cows in
      1,372 herds from 1,758 sires for Jerseys. Functional longevity was defined as the
      number of days from the first calving to culling, death, or censoring. The test
      day SCC was transformed to a linear score, and the resulting SCS were averaged
      within each lactation. The average SCS were grouped into 10 classes. The
      statistical model included the effects of stage of lactation; season of
      production; annual change in herd size; type of milk recording supervision; age
      at first calving; effects of milk, fat, and protein yields, calculated as within
      herd-year-parity deviations; herd-year-season of calving; SCS class; and sire.
      The relative culling rate was calculated for animals in each SCS class after
      accounting for the aforementioned effects. The overall average SCC for Holsteins
      was 167,000 cells/mL, for Ayrshires was 155,000 cells/mL, and for the Jerseys was
      212,000 cells/mL. In all breeds there were no appreciable differences in the
      relative risk of culling among classes of SCS breed averages (i.e., up to a SCS
      of 5). However, as the SCS increased beyond the breed average, the relative risk
      of cows being culled increased considerably. For instance, Holstein, Ayrshire,
      and Jersey cows with the highest classes of SCS had, respectively, a 4.95, 6.73,
      and 6.62 times greater risk of being culled than cows with average SCS.

PMID- 16899695
TI  - Silage chop length and hay supplementation on milk yield, chewing activity, and
      ruminal digestion by dairy cows.
AB  - The effects of whole-plant corn silage (CS) particle size and long unprocessed
      grass hay (LH) supplementation on milk yield, chewing activity, and ruminal
      digestion in dairy cows were evaluated in 2 experiments. In Experiment 1, corn
      silage harvested at fine (6 mm; FCS) or coarse (23 mm; CCS) theoretical cut
      length were fed to 22 lactating Holstein cows. Treatments were 2 total mixed
      rations containing 58% of dry matter (DM) as FCS or CCS. Diet DM intake tended to
      be higher in cows fed FCS than those fed CCS (23.4 vs. 22.1 kg/d). However, milk
      yield and composition, body condition score, and plasma metabolite concentrations
      were not affected by the dietary treatments. In the second experiment, 5
      cannulated Holstein cows were used in a 5 x 5 Latin square design to evaluate the
      effects of the addition of LH to the diets evaluated in Experiment 1 on chewing
      activity and ruminal digestion. Treatments were 5 total mixed rations: FCS-based
      diet plus the addition of 0, 5, or 10% LH (DM basis) and CCS-based diet plus 0 or
      5% LH. Long hay addition linearly decreased DM intake in cows fed FCS-based diets
      (25.0 to 21.7 kg/d), but increased DM intake in those fed CCS-based diets (22.7
      to 27.1 kg/d). The intake of neutral detergent fiber (NDF) increased with LH
      addition in CCS-based diets (7.6 vs. 9.4 kg/d). Rumination time increased (16.8
      to 21.0 min/kg of DM intake) when LH was added to FCS-based diets, but it
      decreased when included in CCS-based diets (18.8 vs. 12.9 min/kg of DM intake).
      Ruminal pH was higher (5.9 vs. 5.7) and lag-time for in situ NDF disappearance
      was shorter (3.5 vs. 8.7 h) for cows fed CCS compared with cows fed FCS. The rate
      of NDF disappearance tended to be higher for the CCS-based diet with 5% LH than
      for the diet with 0% LH (2.0 vs. 4.4 %/h), but solids passage rate was not
      affected by the treatments. These results suggest that addition of LH to FCS
      based diets does not affect ruminal environment or digestion, but depressed DM
      intake. In contrast, addition of LH to CCS-based diets may improve ruminal NDF
      digestion, increasing DM intake by reducing filling effect and time needed for
      rumination.

PMID- 16899694
TI  - Effects of weaning and ionophore supplementation on selected blood metabolites
      and growth in dairy calves.
AB  - Dairy calf weaning results in blood ketone concentrations in excess of mature
      rates of use and can result in excretion of ketones in urine representing a loss
      of energy. Lasalocid is frequently supplemented as an anticoccidial agent in calf
      starters; however, in mature ruminants it is known to alter molar ratios of
      ruminal volatile fatty acids (VFA). Effects of weaning transition and postweaning
      ionophore supplementation on body weight, dry matter (DM) intake, average daily
      gain (ADG), and blood concentrations of glucose, acetoacetate, beta
      hydroxybutyrate (BHBA), lactate, pyruvate, nonesterified fatty acids (NEFA), VFA,
      insulin, and glucagon were examined using Jersey bull calves (n = 24) over 16 wk.
      Calves were blocked into groups of 2 according to birth date and weight and
      randomly assigned to receive either a commercial pelleted starter (control), or
      the same diet containing lasalocid (TRT; 83 mg/kg of DM). Calves were fed milk
      replacer from d 3 to 34 (d 3 to 20 = 454 g/d at 12% solids; d 21 to 34 = 568 g/d
      at 15% solids), from d 35 to 48 calves received both replacer (d 35 to 41 = 454
      g/d; d 42 to 38 = 227 g/d) and free access to control or TRT starter, and from d
      49 to 112 received ad libitum control or TRT. Body weight and jugular blood
      metabolite concentrations were measured and recorded weekly. Postweaning DM
      intake, average daily gain, and feed:gain did not differ between control and TRT
      calves. Glucose and NEFA concentrations did not differ between control and TRT,
      but declined with age. Insulin and glucagon concentrations did not differ between
      control and TRT, but glucagon concentrations increased with weaning. Total VFA
      significantly increased following introduction of solid feed at d 35 in both
      groups with an apparent 1-wk lag in TRT VFA increases compared with control.
      Jugular acetate and butyrate concentrations were greater in control calves than
      TRT calves during wk 7. Propionate concentrations did not differ between control
      and TRT at any time following weaning. Blood BHBA concentrations were greater in
      control than TRT during wk 8 and 9. Thus, consumption of starter supplemented
      with lasalocid delayed peak acetate and butyrate and lowered peak BHBA
      concentrations. However, supplementation at concentrations currently recommended
      for control of coccidiosis did not appear to be sufficient to enhance growth or
      efficiency during the wk 7 to 16 postweaning interval for this sample size.

PMID- 16899697
TI  - A method to define breeding goals for sustainable dairy cattle production.
AB  - The objective of this study was to present a method to define breeding goals for
      sustainable dairy cattle production by adding nonmarket values to market economic
      values for functional traits in the breeding goal. A nonmarket value can
      represent the value of improved animal welfare or societal influences for animal
      production. The nonmarket value for mastitis resistance, conception rate, and
      stillbirth were derived based on how much farmers or breeding companies were
      willing to lose in selection response for milk yield to improve functional
      traits. The desired response for milk yield corresponding to a given percent loss
      was obtained using desired gain indices. By allowing a 5% loss in the selection
      response for milk yield, the nonmarket value was found to be 40.4 euro for
      mastitis resistance, 16.1 euro for conception rate, and 9.7 euro for stillbirth.
      The nonmarket value increased proportionally with increasing loss in the
      selection response for milk yield, but the selection response was lower for
      conception rate than for mastitis resistance because of differences in market
      economic value and heritability. To increase the response for conception rate,
      the nonmarket value was also derived for 2 situations, in which the desired
      responses for milk yield, mastitis resistance, and conception rate were
      specified. The method can be used to define breeding goals for sustainable
      production and to increase the response for traits that are at critically low
      levels. When defining breeding goals for sustainable production, breeding
      organizations should predict the selection response based on market economic
      value and add non-market value for traits with unacceptable selection responses.

PMID- 16899698
TI  - Association of toll-like receptor 4 polymorphisms with somatic cell score and
      lactation persistency in Holstein bulls.
AB  - Mastitis, an inflammatory disease of the mammary gland generally caused by
      intramammary infections, is the most frequently occurring disease in the North
      American dairy industry. Reduced milk yield, milk quality, and lactation
      persistency as well as early culling contribute to the economic losses associated
      with this disease. During intramammary infections, cells of the innate immune
      system become activated through pattern recognition receptors that recognize
      conserved molecular signatures associated with the invading pathogen. The
      quality, timing, and intensity of the host inflammatory and subsequent immune
      response determine the fate of this disease. Toll-like receptor 4 (TLR4) is an
      important pattern recognition receptor that recognizes endotoxins associated with
      gram-negative bacterial infections. Its role in pathogen recognition and
      subsequent initiation of the inflammatory and immune response makes it a suitable
      candidate gene for enhancing disease resistance in Canadian Holsteins. In this
      study, polymorphisms in the TLR4 gene were identified in the Canadian Holstein
      bull population. Genotypes and haplotypes were constructed, and their
      associations with somatic cell score and lactation persistency were determined.
      Sequencing of selective DNA pools was used to reveal polymorphisms in TLR4. Two
      DNA pools were constituted based on high and low estimated breeding values for
      somatic cell scores. A total of 3 single nucleotide polymorphisms (SNP),
      including 1 SNP in a putative promoter region (P-226) and 2 SNP in exon3 (E3+1656
      and E3+2021) of TLR4 were detected. A total of 388 bulls were genotyped for the
      SNP, haplotypes were reconstructed, and their frequencies were obtained.
      Polymorphisms in these regions were found to be associated with estimated
      breeding values for lactation persistency, and somatic cell scores in the
      Canadian Holstein bull population. The unfavorable alleles at P-226 and E3+1656
      were found at a frequency of 40 and 37%, respectively; hence, selection against
      these alleles is promising in Canadian Holsteins. Selection against the
      unfavorable allele, T at E3+2021, is limited because of its low frequency (7%).
      Two frequently occurring haplotypes (GCC and CTC) occurred in 86% of the Canadian
      Holstein bull population chosen for genotyping. The most frequent haplotype (GCC;
      54%) was found to be associated with higher lactation persistency and lower
      somatic cell scores. The transversion SNP in the putative promoter region (P-226)
      was in a potential DNA binding site.

PMID- 16899699
TI  - Use of repeated measures analysis for evaluation of genetic background of dairy
      cattle behavior in automatic milking systems.
AB  - Milking frequencies measured at official test days were used with repeated
      measurement analysis to reveal the environmental and genetic impact on the
      milking frequency of cows in automatic milking systems. Repeated measurements
      were 3 test-day observations per cow within days in milk (DIM) classes, with
      1,216 cows in DIM class 1 (d 0 to 99), from 1,112 cows in DIM class 2 (d 100 to
      199), and from 1,004 cows in DIM class 3 (d 200 to 299) kept in 15 farms.
      Selection criteria for models analyzing repeated measurements were Akaike and
      Schwarz Bayesian values, which favored the autoregressive [AR(1)] covariance
      structure over the compound symmetry model. Results from the AR(1) model
      indicated a significant impact of fixed herd and parity effects. Milking
      frequencies decreased with increasing parities and were greatest for first-parity
      cows. High daily milk yield was associated with higher milking frequencies.
      Heritabilities for milking frequency were 0.16, 0.19, and 0.22 in DIM classes 1,
      2, and 3, respectively, from the AR(1) model. Higher heritabilities in the later
      stage of lactation were due to a substantial reduction of the residual variance.
      Genetic correlations between test-day milk yield and daily milking frequency were
      in the range of 0.46 to 0.57 for all DIM classes and between milking frequency
      and somatic cell score were near zero. For verification of results, milking
      frequencies of the same cows obtained from herd management programs were averaged
      within DIM classes. Heritabilities were slightly above the values from the AR(1)
      model. In conclusion, heritabilities for milking frequency in automatic milking
      systems are moderate enough to incorporate this behavioral trait in a combined
      breeding goal. The inevitable improvement of labor efficiency in dairy cattle
      farming demands such cows going easily and voluntarily in automatic milking
      systems.

PMID- 16899700
TI  - Detection of carryover in automated milk sampling equipment.
AB  - Equipment for sampling milk in automated milking systems may cause carryover
      problems if residues from one sample remain and are mixed with the subsequent
      sample. The degree of carryover can be estimated statistically by linear
      regression models. This study applied various regression analyses to several real
      and simulated data sets. The statistical power for detecting carryover milk
      improved considerably when information about cow identity was included and a
      mixed model was applied. Carryover may affect variation between animals,
      including genetic variation, and thereby have an impact on management decisions
      and diagnostic tools based on the milk content of somatic cells. An extended
      procedure is needed for approval of sampling equipment for automated milking with
      acceptable latitudes of carryover, and this could include the regression approach
      taken in this study.

PMID- 16899701
TI  - Detection and characterization of amplified fragment length polymorphism markers
      for clinical mastitis in Canadian Holsteins.
AB  - Mastitis is the most frequent, complex, and costly disease in dairy cattle.
      Genetic improvement of milk production traits has accompanied an increased
      susceptibility to mastitis. To determine genome-wide quantitative trait locus
      linked markers for mastitis resistance, a total of 200 cows, comprising 100 top
      clinical mastitis- (CM) resistant and 100 top CM-susceptible cows, were screened
      by selective DNA pooling and amplified fragment length polymorphism (AFLP)
      technique. The AFLP analysis on resistant and susceptible pools using 89
      selective primer combinations revealed 27 significant AFLP markers at a false
      discovery rate (FDR) of < 5%. The most promising AFLP marker was then selected
      for further characterization. Individual AFLP genotyping of the marker on all
      selected animals confirmed a significant difference. Sequence analysis detected a
      single nucleotide polymorphism (A<-->G) responsible for the AFLP polymorphism,
      which was named CGIL4. The PCR-RFLP analysis indicated that the frequency of
      allele A was significantly higher in the resistant group. The logistic regression
      analysis demonstrated that the marker was significantly associated with somatic
      cell score, CM residual values, and production traits. Radiation hybrid mapping
      assigned the marker to Bos taurus autosome 22. The present study provides
      promising markers for marker-assisted selection for CM resistance. Our results
      also demonstrated the capability of AFLP on selective DNA pools as a method for
      detection of genome regions containing quantitative trait loci.

PMID- 16899702
TI  - Quantitative trait loci affecting fertility and calving traits in Swedish dairy
      cattle.
AB  - Impaired fertility is the main reason for involuntary culling of dairy cows in
      Sweden. The objective of this study was to map quantitative trait loci (QTL)
      influencing fertility and calving traits in the Swedish dairy cattle population.
      The traits analyzed were number of inseminations, 56-d nonreturn rate, interval
      from calving to first insemination, fertility treatments, heat intensity score,
      stillbirth, and calving performance. A genome scan covering 20 bovine chromosomes
      was performed using 145 microsatellite markers. The mapping population consisted
      of 10 sires and their 417 sons in a granddaughter design. Nine of the sires were
      of the Swedish Red Breed, and one was a Swedish Holstein. Least squares
      regression was used to map loci affecting the analyzed traits, and permutation
      tests were used to set significance thresholds. Cofactors were used in the
      analyses of individual chromosomes to adjust for QTL found on other chromosomes.
      The use of cofactors increased both the number of QTL found and the significance
      level. In the initial analysis, we found 13 suggestive QTL that were mapped to
      chromosomes 6, 7, 9, 11, 13, 15, 20, and 29. When cofactors were included, 30 QTL
      were detected on chromosomes 1, 3, 4, 18, 19, 22, and 25, in addition to the 8
      previously mentioned chromosomes. Some of the results from the cofactor analysis
      may be false positives and require further validation. In conclusion, we were
      able to map several QTL affecting fertility and calving traits in Swedish dairy
      cattle.

PMID- 16899703
TI  - Effects of breed and region on longevity traits through five years of age in
      Brown Swiss, Holstein, and Jersey cows in the United States.
AB  - The objective of this study was to assess breed, and breed x region interactions
      for several longevity-related traits, measured up to 5 yr of age in Brown Swiss,
      Holstein, and Jersey cows in 7 regions of the United States. Data were analyzed
      using logistic, poisson, and linear models, and survival analyses. The traits
      were stayability (yes/no survived to 5 yr of age), number of completed
      lactations, days lived, herd-life, and days in milk (DIM) to 5 yr of age.
      Probable lifetime DIM were also estimated using data from the first 5 yr of age
      of the cows. Herd-life was defined as the days lived up to 5 yr of age minus the
      age at first calving. Days in milk consisted of herd-life up to 5 yr of age minus
      the dry periods. Three data files were analyzed: herds with one breed of cows,
      herds with Holstein and Brown Swiss, and herds with Holstein and Jersey cows.
      Breed x region interaction was usually significant, with larger effects for the
      southern regions. Jerseys obtained largest values for the ratio of DIM to days
      lived, and for the number of completed lactations to 5 yr of age. Brown Swiss had
      the largest probabilities of surviving to 5 yr of age (stayabilities) in all
      regions. For the other traits, the results for Brown Swiss were inconsistent, but
      usually the cows of this breed had shorter herd-life and DIM to 5 yr of age than
      Holsteins. Brown Swiss cows were expected to have more total DIM in their
      lifetime in the Southeast than Holsteins. Survival analysis gave the most readily
      interpretable information, although the linear, poisson, and logistic analyses
      answered slightly different questions. Adjustment for herd size did not modify
      the results.

PMID- 16899704
TI  - Random regression models for male and female fertility evaluation using
      longitudinal binary data.
AB  - A longitudinal Bayesian threshold analysis of insemination outcomes was carried
      out using 2 random regression models with 3 (Model 1) and 5 (Model 2) parameters
      to model the additive genetic values at the liability scale. All insemination
      events of first-parity Holstein cows were used. The outcome of an insemination
      event was treated as a binary response of either a success (1) or a failure (0).
      Thus, all breeding information for a cow, including all service sires, was
      included, thereby allowing for a joint evaluation of male and female fertility.
      An edited data set of 369,353 insemination records from 210,373 first-lactation
      cows was used. On the liability scale, both models included the systematic
      effects of herd-year, month of insemination, technician, and regressions on age
      of service sire and milk yield during the first 100 d of lactation. The random
      effects in the model were the 3 or 5 random regression coefficients specific to
      each cow, the permanent effect of the cow, and the service sire effect. Using
      Model 1, the estimated heritability of an insemination outcome decreased from
      0.035 at d 50 to 0.032 at d 140 and then increased continuously with DIM. The
      genetic correlations for insemination success at different time points ranged
      from 0.83 to 0.99, and their magnitude decreased with an increase in the interval
      between inseminations. A similar trend was observed for heritability and genetic
      correlations using Model 2. However, the average estimate of heritability was
      much higher (0.058) than those obtained using Model 1 or a repeatability model.
      In addition, the estimated genetic correlations followed the same trend as Model
      1, but were lower and with a higher rate of decrease when the interval between
      inseminations increased. The posterior mean of service sire variance was 0.01 for
      both models, and permanent environmental variance was 0.05 and 0.02 for Models 1
      and 2, respectively. Model comparison based on the Bayes factor indicated that
      Model 1 was more plausible, given the data.

PMID- 16899705
TI  - Estimating fatty acid content in cow milk using mid-infrared spectrometry.
AB  - Interest in the fatty acid composition of dairy products is increasing; however,
      the measurement of fatty acids requires using gas-liquid chromatography. Although
      this method is suitable, it involves a time-consuming procedure, expensive
      reagents, and qualified staff. By comparison, the mid-infrared (MIR) spectrometry
      method could be a good alternative for assessing the fatty acid profile of dairy
      products. The objective of this study was to explore the calibration of MIR
      spectrometry for estimating fatty acid concentrations in milk and milk fat.
      Estimated concentrations in milk fat were less reliable than those for the same
      fatty acids in milk. Results also showed that when the fatty acid concentrations
      in milk increased, the efficiency of the infrared analysis method in predicting
      these values simultaneously increased. Selected prediction equations must have a
      high cross-validation coefficient of determination, a high ratio of standard
      error of cross-validation to standard deviation, and good repeatability of
      chromatographic data. Results from this study showed that the calibration
      equations predicting 12:0, 14:0, 16:0, 16:1cis-9, 18:1, and saturated and
      monounsaturated fatty acids in milk could be used. Thus, with its potential for
      use in regular milk recording, this infrared analysis method offers the
      possibility of assessing and improving the quality of milk produced. Indeed, it
      enables the fatty acid composition in milk to be estimated for each cow and the
      estimates to be used as indicator traits to determine the genetic values of
      underlying fatty acid concentrations. The knowledge of these genetic values would
      open up opportunities for animal selection aimed at improving the nutritional
      quality of cow milk.

PMID- 16899706
TI  - Efficacy of two hydrogen peroxide teat disinfectants against Staphylococcus
      aureus and Streptococcus agalactiae.
AB  - An experimental teat dip containing 0.5% hydrogen peroxide as the active
      ingredient was compared with a teat disinfectant also containing 0.5% hydrogen
      peroxide that is commercially available throughout North America. The study was
      conducted under conditions of experimental challenge with a positive control
      following the guidelines recommended by the National Mastitis Council. The
      efficacy of the test product and the positive control product were compared in 45
      cows, with 89 total teats receiving each product after milking during a 10-wk
      study period. There was no significant difference between the experimental
      hydrogen peroxide product and the positive control in new intramammary infections
      caused by Staphylococcus aureus (27.0 and 18.0% in the treatment groups,
      respectively). Additionally, there was no significant difference between the
      experimental product (6.7%) and the positive control groups (4.5%) in new
      intramammary infections caused by Streptococcus agalactiae. Traditional analysis
      of teat skin condition changes supported improved teat skin condition with the
      test disinfectant. After accounting for the correlation of teats within cow,
      significant differences were also observed between the treatment groups for teat
      skin condition. The experimental hydrogen peroxide-based teat disinfectant
      provided efficacy similar to that of the positive control teat disinfectant, with
      significant improvement in teat skin condition and no adverse effects on teat end
      condition.

PMID- 16899707
TI  - Efficiency of use of imported nitrogen, phosphorus, and potassium and potential
      for reducing phosphorus imports on Idaho dairy farms.
AB  - Eight commercial dairies from south central Idaho were surveyed to estimate the
      whole-farm surpluses of N, P, and K and to investigate the possibility of
      reducing P excretions through dietary manipulation. Nitrogen, P, and K imports
      and exports were monitored in a 12-mo period, and samples from the diets, feeds,
      feces, urine, and manure were collected at regular farm visits. Soils from manure
      amended fields were sampled in the spring and fall. In all cases, the largest
      import of N, P, and K to the dairy was with purchased feeds. Major nutrient
      export items were milk and manure and forages, in the case of a dairy with a
      large land base (dairy F). Whole-farm N surplus varied from 90 to 599 t/yr (91 to
      222 kg/yr per cow). The efficiency of use of imported N varied from 25 to 64%,
      with dairy F having the greatest efficiency of imported N use. Phosphorus and K
      surpluses were also significant (average of 29 and 182 t/yr and 12 and 76 kg per
      cow per year, respectively). During the study period, dairy F was a net exporter
      of K. The average efficiency of use of imported P and K was 66 and 58%,
      respectively. Soil P levels in the 30-cm layer were above state threshold
      standards, most likely from overapplication of manure. Soil nitrate-N
      concentrations were also high, but K concentrations were within the accepted
      range. Average P content of the lactating cow diets at the start of the study was
      0.49% and was reduced to 0.38%. The estimated reduction in imported P due to the
      reduced dietary P levels was from 5.7 to 61.4 t/yr per farm, or on average 12 kg
      per cow per year. This study demonstrated that in addition to exports with milk
      and manure, export of nutrients with forages produced on the farm (dairy F) is a
      major factor in reducing whole-farm N, P, and K surpluses.

PMID- 16899708
TI  - Survival rates and productive herd life of dairy cattle in the United States.
AB  - Survival rates and productive herd life were examined for 13.8 million US dairy
      cows that calved from January 1, 1980, through March 2, 2005. Cows that left the
      herd for dairy purposes or were from herds that discontinued Dairy Herd
      Improvement testing were excluded from any calculations to prevent
      underestimation of population longevity. Mean lactation length for cows without
      subsequently recorded lactations ranged from 205 to 235 d across breed-parity
      subsets and were 4 to 29 d longer for parities 2 through 7 than for parity 1.
      Mean survival rates were 73% to parity 2; 50% to parity 3; 32% to parity 4; and
      19, 10, 5, and 2% to parities 5 through 8, respectively. The mean number of
      parities for Holsteins declined from 3.2 for those first calving in 1980 to 2.8
      for those first calving in 1994. Mean numbers of parities for other breeds first
      calving in 1994 were 2.9 for Ayrshires and Brown Swiss, 2.4 for Guernseys, and
      3.2 for Jerseys. Breed means for productive herd life (through parity 8) ranged
      from 28 to 36 mo. All regressions of mean number of parities or mean productive
      herd life on year were negative. The trend for decline of many of those
      indicators of longevity slowed or ended after the early 1990s. Between 31
      (Jersey) and 39% (Guernsey) of herds were made up of first-calf heifers.

PMID- 16899709
TI  - Within- and across-person uniformity of body condition scoring in Danish Holstein
      cattle.
AB  - Body condition scores (BCS) are very useful for dairy herd management and
      breeding programs, but the consistency and quality of recordings made by
      consultants in the field are unknown. The objectives of this study were 1) to
      estimate the agreement in BCS within and among practicing dairy veterinarians and
      2) to provide an indication of the effects of training and the value of
      calibration, and of what efforts need to be made to obtain a validity and
      precision in BCS adequate for management purposes. A total of 2,230 scores were
      recorded by 51 practicing dairy veterinarians and 6 highly trained instructors.
      The 6 instructors were cross-trained to validate calibration consistency in
      assigning BCS. Each individual scored approximately 20 cows twice, with the
      second scoring occurring approximately 2.5 h after the first. Between the 2
      recordings, the respective instructors conducted a training session for the
      practicing veterinarians using other cows. A weighted kappa coefficient was used
      to assess agreement among and within classifiers. Excellent agreement (kappa > or
      = 0.86) was documented between repeated BCS recorded for the same cows by the
      highly trained instructors. In addition, the BCS provided by multiple classifiers
      from the instructor team appeared to be comparable across herds and classifiers.
      This legitimizes the use of BCS for benchmarking at both the cow and the herd
      level. The within-classifier and between-classifier kappa values were in the
      ranges of 0.22 to 0.75 and 0.17 to 0.78, respectively, in the group of practicing
      dairy veterinarians. Many of the veterinarians provided estimates of average BCS
      that differed considerably from the BCS recorded by the instructors. Between
      classifier comparisons of herd BCS are not warranted unless a validation has been
      performed. If scores are collected by multiple classifiers with varying
      experience, a valid but imprecise estimate of the true population mean of BCS may
      be obtained if classifiers are inexperienced. The limited training effort used in
      this study seemed to have brought about substantial improvement in the validity
      and precision of the BCS determined by practicing veterinarians, compared with
      the BCS recorded on the same cows by highly trained classifiers.

PMID- 16899710
TI  - Protoporphyrin IX generation from delta-aminolevulinic acid elicits pulmonary
      artery relaxation and soluble guanylate cyclase activation.
AB  - Protoporphyrin IX is an activator of soluble guanylate cyclase (sGC), but its
      role as an endogenous regulator of vascular function through cGMP has not been
      previously reported. In this study we examined whether the heme precursor delta
      aminolevulinic acid (ALA) could regulate vascular force through promoting
      protoporphyrin IX-elicited activation of sGC. Exposure of endothelium-denuded
      bovine pulmonary arteries (BPA) in organoid culture to increasing concentrations
      of the heme precursor ALA caused a concentration-dependent increase in BPA
      epifluorescence, consistent with increased tissue protoporphyrin IX levels,
      associated with decreased force generation to increasing concentrations of
      serotonin. The force-depressing actions of 0.1 mM ALA were associated with
      increased cGMP-associated vasodilator-stimulated phosphoprotein (VASP)
      phosphorylation and increased sGC activity in homogenates of BPA cultured with
      ALA. Increasing iron availability with 0.1 mM FeSO(4) inhibited the decrease in
      contraction to serotonin and increase in sGC activity caused by ALA, associated
      with decreased protoporphyrin IX and increased heme. Chelating endogenous iron
      with 0.1 mM deferoxamine increased the detection of protoporphyrin IX and force
      depressing activity of 10 microM ALA. The inhibition of sGC activation with the
      heme oxidant 10 muM 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) attenuated
      the force depressing actions of an NO donor without altering the actions of ALA.
      Thus control of endogenous formation of protoporphyrin IX from ALA by the
      availability of iron is potentially a novel physiological mechanism of
      controlling vascular function through regulating the activity of sGC.

PMID- 16899711
TI  - Positive transcriptional regulatory element located within exon 1 of elastin
      gene.
AB  - Elastin gene transcription is cell type specific and developmentally regulated,
      but the promoter often exhibits relatively weak activity in transient
      transfections of cells that express elastin at high levels. To search for
      positive-acting regulatory sequences, we isolated genomic clones spanning the
      mouse elastin gene and extensive 5'- and 3'-flanking regions. Restriction
      fragments of potential regulatory regions were ligated 5' or 3' relative to the
      active promoter to test for enhancer activity in transient transfections of fetal
      rat lung fibroblasts, which express elastin at high levels, and distal lung
      epithelial cells, which do not express detectable elastin. Fragments of intron 1
      did not exhibit significant enhancer activity. Inclusion of the 84-bp exon 1 and
      adjacent 5'-untranslated region increased activity of the elastin promoter
      approximately sixfold compared with parental constructs. Transfections with
      constructs of varying promoter length showed that as little as 40 bp of the 5'
      end of exon 1 confers enhanced activity in elastin-expressing rat lung
      fibroblasts, but these constructs had variable activity in lung epithelial cell
      lines. This region, localized between the transcription start site and extending
      into exon 1, binds Sp1 in nuclear extracts from elastin-expressing cells. These
      studies indicate a role for the 5' end of the first exon of the elastin gene in
      regulating strong transcriptional activity in elastogenic cells.

PMID- 16899712
TI  - Nutrient modulation of intestinal gas dynamics in healthy humans: dependence on
      caloric content and meal consistency.
AB  - The actions of nutrients on gut transit of liquids and solids have been
      extensively studied, but the effects of meal ingestion on intestinal gas flow are
      unexplored. We hypothesized that meals of varying caloric content and consistency
      modulate gas transit to different degrees. Nine healthy volunteers underwent
      jejunal perfusion of physiological gas mixtures at 12 ml.min(-1).3 h, with
      ingestion of nothing (control), water (240 ml), 240-kcal liquid meals, and 240
      kcal solid meals at the end of the second hour in separate studies. Gas was
      quantified from an intrarectal catheter. After an initial lag phase, gas
      evacuation approached steady state by the end of the fasting period. Solid and
      liquid caloric meals increased total gas volumes evacuated from 5-40 min after
      ingestion vs. control studies (P < 0.05). These increases resulted from increased
      numbers of bolus gas evacuations (P < 0.05), whereas bolus volumes, pressures,
      and flow rates were similar for all test conditions. Solid and liquid caloric
      meals elicited similar effects on bolus gas dynamic parameters, whereas water did
      not affect these measures vs. control (NS, not significant). Both caloric meals
      and the noncaloric liquid meal increased continuous gas flow, which represented
      <2% of total gas expulsion. In conclusion, caloric meals promote bolus gas
      transit in healthy humans, whereas noncaloric liquids have no effect. Solids
      stimulate early postprandial gas dynamics to the same extent as liquid meals of
      similar caloric content. Thus modulatory effects of meals on intestinal gas
      transit depend on their caloric content but not their consistency.

PMID- 16899713
TI  - Focal adhesion kinase protein levels in gut epithelial motility.
AB  - Mucosal healing requires migration and proliferation. Most studies of focal
      adhesion kinase (FAK), a protein that regulates motility, proliferation, and
      apoptosis, have focused on rapid phosphorylation. We reported lower FAK protein
      levels in motile Caco-2 colon cancer cells and postulated that this reduction in
      FAK available for activation might impact cell migration and mucosal healing.
      Therefore, total and active FAK (FAK(397)) immunoreactivity was assessed at the
      migrating fronts of human Caco-2 and rat IEC-6 intestinal epithelial cells. Caco
      2 and IEC-6 motility, quantitated as migration into linear or circular wounds,
      was examined following FAK protein inhibition by small interfering RNA (siRNA).
      FAK protein stability and mRNA expression were ascertained by cycloheximide
      decay, RT-PCR, and in situ hybridization in static and migrating Caco-2 cells.
      Cells at the migrating front of Caco-2 and IEC-6 monolayers exhibited lower
      immunostaining for both total and activated FAK than cells immediately behind the
      front. Western blot analysis also demonstrated diminished FAK protein levels in
      motile cells by >/=30% in both the differential density seeding and multiple
      scrape models. siRNA FAK protein inhibition enhanced motility in both the linear
      scrape (20% in Caco-2) and circular wound (16% in Caco-2 and 19% in IEC-6 cells)
      models. FAK protein degradation did not differ in motile and static Caco-2 cells
      and was unaffected by FAK(397) phosphorylation, but FAK mRNA was lower in
      migrating Caco-2 cells. Thus FAK protein abundance appears regulated at the mRNA
      level during gut epithelial cell motility and may influence epithelial cell
      migration coordinately with signals that modify FAK phosphorylation.

PMID- 16899714
TI  - Isolation and characterization of cholangiocyte primary cilia.
AB  - Primary cilia are distinct organelles expressed by many vertebrate cells,
      including cholangiocytes; however, their functions remain obscure. To begin to
      explore the physiological role of these organelles in the liver, we described the
      morphology and structure of cholangiocyte cilia and developed new approaches for
      their isolation. Primary cilia were present only in bile ducts and were not
      observed in hepatocytes or in hepatic arterial or portal venous endothelial
      cells. Each cholangiocyte possesses a single cilium that extends from the apical
      membrane into the bile duct lumen. In addition, the length of the cilia was
      proportional to the bile duct diameter. We reproducibly isolated enriched
      fractions of cilia from normal rat and mouse cholangiocytes by two different
      approaches as assessed by scanning electron, transmission electron, and confocal
      microscopy. The purity of isolated ciliary fractions was further analyzed by
      Western blot analysis using acetylated tubulin as a ciliary marker and P2Y(2) as
      a nonciliary cell membrane marker. These novel techniques produced enriched
      ciliary fractions of sufficient purity and quantity for light and electron
      microscopy and for biochemical analyses. They will permit further assessment of
      the role of primary cilia in normal and pathological conditions.

PMID- 16899715
TI  - CD23-mediated transport of IgE/immune complexes across human intestinal
      epithelium: role of p38 MAPK.
AB  - We previously reported that CD23/FcepsilonRII (low-affinity IgE receptor) is
      expressed on human intestinal epithelial cells and is responsible for
      transepithelial transport of IgE. In this study, we compared the transport of IgE
      with that of immune complexes in both the apical-to-serosal and the serosal-to
      apical directions across HT29 epithelial cell layers and examined the effects of
      two p38 MAPK inhibitors, SKF86002 and SB203580, on the expression and function of
      CD23. Our study showed that both p38 MAPK inhibitors at 10 microM significantly
      inhibited constitutive and IL-4-upregulated CD23 protein expression in epithelial
      cells. Both inhibitors, in a concentration-dependent manner, also significantly
      reduced IgE binding and uptake into cells. Transepithelial transport of IgE and
      immune complexes across the epithelial barrier were similarly inhibited. IL-4
      upregulated the phosphorylation and activity of p38 MAPK and the phosphorylation
      of the downstream substrate MAPKAPK-2 (MK-2). The inhibitors exerted effects in
      the pathway post the p38 MAPK; SB203580 significantly inhibited the
      phosphorylation of MK-2. Our results indicate that CD23 expression in these human
      intestinal epithelial cells is mediated through the p38 MAPK pathway and that
      inhibition of p38 MAPK consequently interferes with the transport of IgE and
      immune complexes across the intestinal epithelial barrier.

PMID- 16899717
TI  - Effects of sensing behavior on a latency code.
AB  - Sensory information is often acquired through active exploration, yet relatively
      little is known about how neurons encode sensory stimuli in the context of
      natural patterns of sensing behavior. We examined the effects of sensing behavior
      on a spike latency code in the active electrosensory system of mormyrid fish.
      These fish actively probe their environment by emitting brief electric organ
      discharge (EOD) pulses. Nearby objects alter the spatial pattern of current
      flowing through the skin. These changes are encoded by small shifts in the
      latency of individual electroreceptor afferent spikes after the EOD. In nature,
      the temporal pattern of EOD intervals is highly structured and varies depending
      on the behavioral context. We performed experiments in which we varied both the
      EOD amplitude and the intervals between EODs to understand how sensing behavior
      affects afferent latency coding. We use white-noise stimuli and linear filter
      estimation methods to develop simple models characterizing the dependence of
      afferent spike latency on the preceding sequence of EOD intervals and amplitudes.
      Comparing the predictions of these models with actual afferent responses for
      natural patterns of EOD intervals and amplitudes reveals an unexpectedly rich
      interplay between sensing behavior and stimulus encoding. Implications of our
      results for how afferent spike latency is decoded at central stages of
      electrosensory processing are discussed.

PMID- 16899718
TI  - Induction of inducible cAMP early repressor expression in nucleus accumbens by
      stress or amphetamine increases behavioral responses to emotional stimuli.
AB  - Previous research has shown that cAMP response element (CRE)-mediated
      transcription is activated in the nucleus accumbens, a major brain reward region,
      by a variety of environmental stimuli and contributes to neuroadaptations to
      these stimuli. CRE-binding protein (CREB) is the most studied activator of CRE
      transcription and has been implicated in this brain region as a gating mechanism
      for behavioral responses to emotional stimuli. Little attention, however, has
      been given to naturally occurring inhibitors of CRE-mediated transcription, such
      as the inducible cAMP early repressor (ICER), an inhibitory product of the CRE
      modulator gene. In the present study, we investigated the extent to which ICER is
      induced in the nucleus accumbens by two types of environmental stimuli, stress
      and amphetamine, and characterized how induction of ICER in this region affects
      complex behavior. We show that stress and amphetamine each induces ICER
      expression and that overexpression of ICER in the nucleus accumbens, using viral
      mediated gene transfer, increases behavioral responses to both rewarding and
      aversive emotional stimuli. For example, ICER overexpression increases
      sensitivity to amphetamine-stimulated locomotor activity as well as to natural
      rewards such as sucrose and social grooming. However, ICER overexpression also
      increases measures of anxiety in the elevated plus maze and neophobia to novel
      tastes. Finally, ICER produces an antidepressant-like effect in the forced swim
      test, further indication of an enhanced active response to stress. These results
      suggest that ICER is an important mechanism for modulating CRE-mediated
      transcription in the nucleus accumbens.

PMID- 16899719
TI  - Discrete innervation of murine taste buds by peripheral taste neurons.
AB  - The peripheral taste system likely maintains a specific relationship between
      ganglion cells that signal a particular taste quality and taste bud cells
      responsive to that quality. We have explored a measure of the receptoneural
      relationship in the mouse. By injecting single fungiform taste buds with
      lipophilic retrograde neuroanatomical markers, the number of labeled geniculate
      ganglion cells innervating single buds on the tongue were identified. We found
      that three to five ganglion cells innervate a single bud. Injecting neighboring
      buds with different color markers showed that the buds are primarily innervated
      by separate populations of geniculate cells (i.e., multiply labeled ganglion
      cells are rare). In other words, each taste bud is innervated by a population of
      neurons that only connects with that bud. Palate bud injections revealed a
      similar, relatively exclusive receptoneural relationship. Injecting buds in
      different regions of the tongue did not reveal a topographic representation of
      buds in the geniculate ganglion, despite a stereotyped patterned arrangement of
      fungiform buds as rows and columns on the tongue. However, ganglion cells
      innervating the tongue and palate were differentially concentrated in lateral and
      rostral regions of the ganglion, respectively. The principal finding that small
      groups of ganglion cells send sensory fibers that converge selectively on a
      single bud is a new-found measure of specific matching between the two principal
      cellular elements of the mouse peripheral taste system. Repetition of the
      experiments in the hamster showed a more divergent innervation of buds in this
      species. The results indicate that whatever taste quality is signaled by a murine
      geniculate ganglion neuron, that signal reflects the activity of cells in a
      single taste bud.

PMID- 16899721
TI  - Background synaptic activity is sparse in neocortex.
AB  - Neurons are continually exposed to background synaptic activity in vivo. This is
      thought to influence neural information processing, but background levels of
      excitation and inhibition remain controversial. Here we show, using whole-cell
      recordings in anesthetized rats, that spontaneous depolarizations ("Up states")
      in neocortical pyramidal neurons are driven by sparse, mostly excitatory synaptic
      activity (less than five inputs per millisecond; approximately 10% inhibitory).
      The mean synaptic conductance change is small (<10 nS at the soma) and opposed by
      anomalous rectification, resulting in a net increase in input resistance during
      Up states. These conditions enhance the effectiveness of each synapse at
      depolarized potentials. Hence, neocortical networks are relatively quiet at rest,
      and the effect of synaptic background is weaker than previously thought.

PMID- 16899720
TI  - The structure of multi-neuron firing patterns in primate retina.
AB  - Current understanding of many neural circuits is limited by our ability to
      explore the vast number of potential interactions between different cells. We
      present a new approach that dramatically reduces the complexity of this problem.
      Large-scale multi-electrode recordings were used to measure electrical activity
      in nearly complete, regularly spaced mosaics of several hundred ON and OFF
      parasol retinal ganglion cells in macaque monkey retina. Parasol cells exhibited
      substantial pairwise correlations, as has been observed in other species,
      indicating functional connectivity. However, pairwise measurements alone are
      insufficient to determine the prevalence of multi-neuron firing patterns, which
      would be predicted from widely diverging common inputs and have been hypothesized
      to convey distinct visual messages to the brain. The number of possible multi
      neuron firing patterns is far too large to study exhaustively, but this problem
      may be circumvented if two simple rules of connectivity can be established: (1)
      multi-cell firing patterns arise from multiple pairwise interactions, and (2)
      interactions are limited to adjacent cells in the mosaic. Using maximum entropy
      methods from statistical mechanics, we show that pairwise and adjacent
      interactions accurately accounted for the structure and prevalence of multi
      neuron firing patterns, explaining approximately 98% of the departures from
      statistical independence in parasol cells and approximately 99% of the departures
      that were reproducible in repeated measurements. This approach provides a way to
      define limits on the complexity of network interactions and thus may be relevant
      for probing the function of many neural circuits.

PMID- 16899722
TI  - Compensation of inositol 1,4,5-trisphosphate receptor function by altering sarco
      endoplasmic reticulum calcium ATPase activity in the Drosophila flight circuit.
AB  - Ionic Ca2+ functions as a second messenger to control several intracellular
      processes. It also influences intercellular communication. The release of Ca2+
      from intracellular stores through the inositol 1,4,5-trisphosphate receptor
      (InsP3R) occurs in both excitable and nonexcitable cells. In Drosophila, InsP3R
      activity is required in aminergic interneurons during pupal development for
      normal flight behavior. By altering intracellular Ca2+ and InsP3 levels through
      genetic means, we now show that signaling through the InsP3R is required at
      multiple steps for generating the neural circuit required in air puff-stimulated
      Drosophila flight. Decreased Ca2+ release in aminergic neurons during development
      of the flight circuit can be compensated by reducing Ca2+ uptake from the cytosol
      to intracellular stores. However, this mode of increasing intracellular Ca2+ is
      insufficient for maintenance of flight patterns over time periods necessary for
      normal flight. Our study suggests that processes such as maintenance of wing
      posture and formation of the flight circuit require InsP3 receptor function at a
      slow timescale and can thus be modulated by altering levels of cytosolic Ca2+ and
      InsP3. In contrast, maintenance of flight patterns probably requires fast
      modulation of Ca2+ levels, in which the intrinsic properties of the InsP3R play a
      pivotal role.

PMID- 16899723
TI  - Climbing fiber-evoked endocannabinoid signaling heterosynaptically suppresses
      presynaptic cerebellar long-term potentiation.
AB  - Endocannabinoid signaling has been demonstrated to mediate depolarization-induced
      suppression of excitation at climbing fiber (CF) and parallel fiber (PF) synapses
      onto cerebellar Purkinje cells. Here, we show that CF-evoked release of
      cannabinoids (CBs) additionally suppresses a presynaptic form of long-term
      potentiation (LTP) at PF synapses. PF-LTP can be induced by 8 Hz PF tetanization
      but is blocked when the PF tetanization is paired with 4 or 1 Hz CF coactivation.
      CF activity can be substituted for by bath application of the CB receptor agonist
      WIN55,212-2 [R(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo[1,2,3-de]
      1,4-benzoxazinyl]-(1-naphthalenyl) methanone]. In the presence of the CB1
      receptor antagonist AM251 [N-1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-1
      piperidinyl-1H-pyrazole-3-carboxamide], CF activity no longer suppresses PF-LTP.
      Presynaptic potentiation can also be obtained by the adenylyl cyclase activator
      forskolin. WIN55,212-2 blocked this forskolin-mediated enhancement, showing that
      CB1 receptor activation interferes with the adenylyl cyclase-protein kinase A
      cascade, which participates in LTP induction. CF activity has been described to
      promote the induction of postsynaptic PF-long-term depression (LTD) and to impair
      postsynaptic PF-LTP. Our observation that CF activity blocks the induction of
      presynaptic LTP suggests that the CF input controls all forms of presynaptic and
      postsynaptic PF plasticity and that CF activity provides a "safety lock" to
      prevent an enhancement of transmitter release while postsynaptic AMPA receptor
      function is downregulated during LTD.

PMID- 16899724
TI  - c-Jun N-terminal kinase activation responses induced by hippocampal kindling are
      mediated by reactive astrocytes.
AB  - Hippocampal kindling, a model of mesial temporal lobe epilepsy, is developed
      through repetitive stimulation of the hippocampus and leads to increased after
      discharges as measured by EEG and an enduring seizure-prone state. Synthesis of
      new proteins is thought to form the basis for sustained seizure-induced
      physiological and/or pathological changes in synaptic reorganization and
      apoptotic/necrotic neuronal death. Here we examined the effect of kindling on
      stimulus-induced c-Jun N-terminal kinase (JNK) and p38 phosphorylation, events
      postulated to lie upstream of seizure-induced changes in gene transcription. We
      found that stimulus-induced phosphorylation of JNK, but not of p38, is
      significantly enhanced in kindled animals compared with their naive counterparts
      in the CA1 subregion of the hippocampus. Immunofluorescent staining confirmed
      this region-specific pattern of JNK activation and revealed that reactive
      astrocytes mediate this effect. Astrocyte proliferation and hypertrophy, as well
      as upregulation of vimentin protein levels, common markers of astrogliosis, were
      present after 4 d of kindling. Moreover, this reactive astrogliosis was
      associated with neuronal death as visualized with Fluoro-jade B and anti-active
      caspase-3 staining. Stimulus-induced phosphorylation of the JNK substrate
      paxillin was enhanced in kindled animals, but not that of c-Jun. Moreover, a pan
      antibody against MAPK/CDK (mitogen-activated protein kinases/cyclin-dependent
      kinase) substrates indicated the presence of phosphorylated proteins in
      cytosolic, membrane, and nuclear fractions. The consequence of these
      phosphorylation events is not completely understood, but these findings suggest a
      selective astrocytic signaling response to aberrant synaptic activity, signaling
      that may modulate kindling progression and/or neuronal death.

PMID- 16899725
TI  - Lesions of the basolateral amygdala disrupt conditioning based on the retrieved
      representations of motivationally significant events.
AB  - One recent perspective (Blundell et al., 2001; 2003; Killcross and Blundell,
      2002; Balleine et al. 2003) on the function of the basolateral region of the
      amygdala (BLA) suggests that it plays an important role in the representation of
      the sensory features of motivationally significant events. This predicts that
      lesions of the BLA will not produce a decrement in performance in conditioning
      procedures based on the formation of associations between the sensory aspects of
      neutral events but will interfere with conditioning based on associations between
      neutral cues and motivationally significant events. This prediction is supported
      by the evidence that BLA lesions were without effect on a sensory preconditioning
      procedure (experiment 1A) that used neutral cues but that BLA lesions did
      significantly impair representation-mediated conditioning (experiment 1B) when
      the target cues were motivationally significant at the time of training. These
      results demonstrate that animals with lesions of the BLA can represent the
      sensory aspects of neutral events but not the sensory aspects of motivationally
      significant events.

PMID- 16899726
TI  - Integration of visuospatial and effector information during symbolically cued
      limb movements in monkey lateral intraparietal area.
AB  - Natural behavior requires close but flexible coordination between attention,
      defined as selection for perception, and action. In recent years a distributed
      network including the lateral intraparietal area (LIP) has been implicated in
      visuospatial selection for attention and rapid eye movements (saccades), but the
      relation between the attentional and motor functions of this area remains
      unclear. Here we tested LIP neurons in a task that involved not an ocular but a
      manual operant response. Monkeys viewed a display containing one cue and several
      distractors and reported the orientation of the cue (right- or left-facing) by
      releasing one of two bars grasped, respectively, with the right or left hand. The
      movement in this task thus was associated with (cued by), but not directed
      toward, the visual stimulus. A large majority of neurons responded more when the
      cue rather than when a distractor was in their receptive field, suggesting that
      they contribute to the attentional selection of the cue. A fraction of these
      neurons also was modulated by limb release, thus simultaneously encoding cue
      location and the active limb. The results suggest that the LIP links behaviorally
      relevant visual information with motor variables relevant for solving a task in a
      wide range of circumstances involving goal-directed or symbolically cued
      movements and eye as well as limb movements. A central function of the LIP may be
      to coordinate visual and motor selection during a wide variety of behaviors.

PMID- 16899727
TI  - Central and medial amygdaloid brain-derived neurotrophic factor signaling plays a
      critical role in alcohol-drinking and anxiety-like behaviors.
AB  - Brain-derived neurotrophic factor (BDNF) is a member of the nerve growth factor
      family of neurotrophins and plays a vital role in synaptic plasticity. This study
      investigated the involvement of the amygdaloid BDNF system in molecular
      mechanisms underlying anxiety and alcohol-drinking behaviors. Male Sprague Dawley
      rats were cannulated targeting central amygdala (CeA), medial amygdala (MeA), or
      basolateral amygdala (BLA), and BDNF expression was manipulated using an
      antisense oligodeoxynucleotide (ODN) strategy. Anxiety-like and alcohol-drinking
      behaviors were measured after infusion of BDNF sense and antisense ODNs with or
      without BDNF coinfusion, using the elevated plus-maze test and two-bottle free
      choice paradigm, respectively. Here we report that BDNF antisense ODN infusions
      into the CeA and MeA, but not BLA, provoked anxiety-like behaviors in rats, which
      were rescued by BDNF coinfusion. The levels of BDNF, p-ERK1/2 (phosphorylated
      extracellular signal-regulated kinases 1/2), and p-CREB (phosphorylated cAMP
      responsive-element binding protein) were decreased by BDNF antisense, but not by
      sense, ODN infusions, which were restored to normal after BDNF coinfusions.
      Furthermore, BDNF antisense ODN infusions into the CeA or MeA, but not into BLA,
      increased alcohol intake, which was attenuated by BDNF coinfusions. These novel
      results suggest that decreased BDNF levels in the CeA and MeA, but not in the
      BLA, are crucial in regulating alcohol-drinking and anxiety-like behaviors in
      rats.

PMID- 16899728
TI  - Tissue injury regulates serotonin 1D receptor expression: implications for the
      control of migraine and inflammatory pain.
AB  - The anti-migraine action of "triptan" drugs involves the activation of serotonin
      subtype 1D (5-HT1D) receptors expressed on "pain-responsive" trigeminal primary
      afferents. In the central terminals of these nociceptors, the receptor is
      concentrated on peptidergic dense core vesicles (DCVs) and is notably absent from
      the plasma membrane. Based on this arrangement, we hypothesized that in the
      resting state the receptor is not available for binding by a triptan, but that
      noxious stimulation of these afferents could trigger vesicular release of DCVs,
      thus externalizing the receptor. Here we report that within 5 min of an acute
      mechanical stimulus to the hindpaw of the rat, there is a significant increase of
      5-HT1D-immunoreactivity (IR) in the ipsilateral dorsal horn of the spinal cord.
      We suggest that these rapid immunohistochemical changes reflect redistribution of
      sequestered receptor to the plasma membrane, where it is more readily detected.
      We also observed divergent changes in 5-HT1D-IR in inflammatory and nerve-injury
      models of persistent pain, occurring at least in part through the regulation of 5
      HT1D-receptor gene expression. Finally, we found that 5-HT1D-IR is unchanged in
      the spinal cord dorsal horn of mice with a deletion of the gene encoding the
      neuropeptide substance P. This result differs from that reported for the partial
      differential-opioid receptor, which is also sorted to DCVs, but is greatly
      reduced in preprotachykinin mutant mice. We suggest that a "pain"-triggered
      regulation of 5-HT1D-receptor expression underlies the effectiveness of triptans
      for the treatment of migraine. Moreover, the widespread expression of 5-HT1D
      receptor in somatic nociceptive afferents suggests that triptans could, in
      certain circumstances, treat pain in nontrigeminal regions of the body.

PMID- 16899729
TI  - Activity bidirectionally regulates AMPA receptor mRNA abundance in dendrites of
      hippocampal neurons.
AB  - Activity-dependent regulation of synaptic AMPA receptor (AMPAR) number is
      critical to NMDA receptor (NMDAR)-dependent synaptic plasticity. Using
      quantitative high-resolution in situ hybridization, we show that mRNAs encoding
      the AMPA-type glutamate receptor subunits (GluRs) 1 and 2 are localized to
      dendrites of hippocampal neurons and are regulated by paradigms that alter
      synaptic efficacy. A substantial fraction of synaptic sites contain AMPAR mRNA,
      consistent with strategic positioning and availability for "on-site" protein
      synthesis. NMDAR activation depletes dendritic levels of AMPAR mRNAs. The
      decrease in mRNA occurs via rise in intracellular Ca2+, activation of
      extracellular signal-regulated kinase/mitogen-activated protein kinase signaling,
      and transcriptional arrest at the level of the nucleus. The decrease in mRNA is
      accompanied by a long-lasting reduction in synaptic AMPAR number, consistent with
      reduced synaptic efficacy. In contrast, group I metabotropic GluR signaling
      promotes microtubule-based trafficking of existing AMPAR mRNAs from the soma to
      dendrites. Bidirectional regulation of dendritic mRNA abundance represents a
      potentially powerful means to effect long-lasting changes in synaptic strength.

PMID- 16899730
TI  - The long and the short of it: relational memory impairments in amnesia, even at
      short lags.
AB  - Classic studies of amnesia led to characterizations of hippocampal function
      emphasizing involvement in long-term memory rather than short-term (or working)
      memory. In two experiments, we show that when memory for relations among co
      occurring items is tested, hippocampal amnesia results in a deficit even at very
      short lags. Hence, we find evidence for hippocampal involvement in relational
      memory, even at short lags normally considered the province of working memory.

PMID- 16899731
TI  - The role of the ventromedial prefrontal cortex in abstract state-based inference
      during decision making in humans.
AB  - Many real-life decision-making problems incorporate higher-order structure,
      involving interdependencies between different stimuli, actions, and subsequent
      rewards. It is not known whether brain regions implicated in decision making,
      such as the ventromedial prefrontal cortex (vmPFC), use a stored model of the
      task structure to guide choice (model-based decision making) or merely learn
      action or state values without assuming higher-order structure as in standard
      reinforcement learning. To discriminate between these possibilities, we scanned
      human subjects with functional magnetic resonance imaging while they performed a
      simple decision-making task with higher-order structure, probabilistic reversal
      learning. We found that neural activity in a key decision-making region, the
      vmPFC, was more consistent with a computational model that exploits higher-order
      structure than with simple reinforcement learning. These results suggest that
      brain regions, such as the vmPFC, use an abstract model of task structure to
      guide behavioral choice, computations that may underlie the human capacity for
      complex social interactions and abstract strategizing.

PMID- 16899732
TI  - Reward-related cortical inputs define a large striatal region in primates that
      interface with associative cortical connections, providing a substrate for
      incentive-based learning.
AB  - The anterior cingulate and orbital cortices and the ventral striatum process
      different aspects of reward evaluation, whereas the dorsolateral prefrontal
      cortex and the dorsal striatum are involved in cognitive function. Collectively,
      these areas are critical to decision making. We mapped the striatal area that
      receives information about reward evaluation. We also explored the extent to
      which terminals from reward-related cortical areas converge in the striatum with
      those from cognitive regions. Using three-dimensional-rendered reconstructions of
      corticostriatal projection fields along with two-dimensional chartings, we
      demonstrate the reward and cognitive territories in the primate striatum and show
      the convergence between these cortical inputs. The results show two labeling
      patterns: a focal projection field that consists of densely distributed terminal
      patches, and a diffuse projection consisting of clusters of fibers, extending
      throughout a wide area of the striatum. Together, these projection fields
      demonstrate a remarkably large, rostral, reward-related striatal territory that
      reaches into the dorsal striatum. Fibers from different reward-processing and
      cognitive cortical areas occupy both separate and converging territories.
      Furthermore, the diffuse projection may serve a separate integrative function by
      broadly disseminating general cortical activity. These findings show that the
      rostral striatum is in a unique position to mediate different aspects of
      incentive learning. Furthermore, areas of convergence may be particularly
      sensitive to dopamine modulation during decision making and habit formation.

PMID- 16899733
TI  - Cerebellar cortical molecular layer inhibition is organized in parasagittal
      zones.
AB  - Molecular layer inhibitory interneurons generate on-beam and off-beam inhibition
      in the cerebellar cortex that is hypothesized to control the timing and/or
      spatial patterning of Purkinje cell discharge. On- and off-beam inhibition has
      been assumed to be spatially uniform and continuous within a folium. Using
      flavoprotein autofluorescence optical imaging in the mouse cerebellar cortex in
      vivo, this study demonstrates that the inhibition evoked by parallel fiber and
      peripheral stimulation results in parasagittal bands of decreases in fluorescence
      that correspond to zebrin II-positive bands. The parasagittal bands of decreased
      fluorescence are abolished by GABA(A) antagonists and reflect the activity of
      molecular layer interneurons on their targets. The same banding pattern was
      observed using Ca2+ imaging. The bands produce spatially specific decreases in
      the responses to peripheral input. Therefore, molecular layer inhibition is
      compartmentalized into zebrin II parasagittal domains that differentially
      modulate the spatial pattern of cerebellar cortical activity.

PMID- 16899734
TI  - Pharmacological activation of mGlu4 metabotropic glutamate receptors inhibits the
      growth of medulloblastomas.
AB  - Moving from the evidence that activation of type 4 metabotropic glutamate (mGlu4)
      receptors inhibits proliferation and promotes differentiation of cerebellar
      granule cell neuroprogenitors, we examined the expression and function of mGlu4
      receptors in medulloblastoma cells. mGlu4 receptors were expressed in 46 of 60
      human medulloblastoma samples. Expression varied in relation to the histotype
      (nodular desmoplastic>classic>>large-cell anaplastic) and was inversely related
      to tumor severity, spreading, and recurrence. mGlu4 receptors were also found in
      D283med, D341med, and DAOY medulloblastoma cell lines, where receptor activation
      with the selective enhancer PHCCC inhibited adenylyl cyclase and the
      phosphatidylinositol-3-kinase pathway without affecting the mitogen-activated
      protein kinase, Sonic Hedgehog, and Wnt pathways. Interestingly, mGlu4 receptor
      activation reduced DNA synthesis and cell proliferation in all three cell lines.
      This effect was abrogated by the phosphatidylinositol-3-kinase inhibitor LY294002
      [2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one]. In in vivo experiments,
      repeated subcutaneous injections of N-phenyl-7-(hydroxyimino)cyclopropa[b]chromen
      1a-carboxamide (PHCCC) reduced the growth of D283med and DAOY cell xenografts in
      nude mice. More remarkably, subcutaneous or intracranial injections of PHCCC
      during the first week of life prevented the development of medulloblastomas in
      mice lacking one Patched-1 allele and x-irradiated 1 d after birth. These data
      suggest that mGlu4 receptor enhancers are promising drugs for the treatment of
      medulloblastomas.

PMID- 16899735
TI  - Calcium activation of the LMO4 transcription complex and its role in the
      patterning of thalamocortical connections.
AB  - Lasting changes in neuronal connectivity require calcium-dependent gene
      expression. Here we report the identification of LIM domain-only 4 (LMO4) as a
      mediator of calcium-dependent transcription in cortical neurons. Calcium influx
      via voltage-sensitive calcium channels and NMDA receptors contributes to
      synaptically induced LMO4-mediated transactivation. LMO4-mediated transcription
      is dependent on signaling via calcium/calmodulin-dependent protein (CaM) kinase
      IV and microtubule-associated protein (MAP) kinase downstream of synaptic
      stimulation. Coimmunoprecipitation experiments indicate that LMO4 can form a
      complex with cAMP response element-binding protein (CREB) and can interact with
      cofactor of LIM homeodomain protein 1 (CLIM1) and CLIM2. To evaluate the role of
      LMO4 in vivo, we examined the consequences of conditional loss of lmo4 in the
      forebrain, using the Cre-Lox gene-targeting strategy. The organization of the
      barrel field in somatosensory cortex is disrupted in mice in which lmo4 is
      deleted conditionally in the cortex. Specifically, in contrast to controls,
      thalamocortical afferents in conditional lmo4 null mice fail to segregate into
      distinct barrel-specific domains. These observations identify LMO4 as a calcium
      dependent transactivator that plays a key role in patterning thalamocortical
      connections during development.

PMID- 16899736
TI  - The current status and environmental impacts of glyphosate-resistant crops: a
      review.
AB  - Glyphosate [N-(phosphonomethyl) glycine]-resistant crops (GRCs), canola (Brassica
      napus L.), cotton (Gossypium hirsutum L.), maize (Zea mays L.), and soybean
      [Glycine max (L.) Merr.] have been commercialized and grown extensively in the
      Western Hemisphere and, to a lesser extent, elsewhere. Glyphosate-resistant
      cotton and soybean have become dominant in those countries where their planting
      is permitted. Effects of glyphosate on contamination of soil, water, and air are
      minimal, compared to some of the herbicides that they replace. No risks have been
      found with food or feed safety or nutritional value in products from currently
      available GRCs. Glyphosate-resistant crops have promoted the adoption of reduced-
      or no-tillage agriculture in the USA and Argentina, providing a substantial
      environmental benefit. Weed species in GRC fields have shifted to those that can
      more successfully withstand glyphosate and to those that avoid the time of its
      application. Three weed species have evolved resistance to glyphosate in GRCs.
      Glyphosate-resistant crops have greater potential to become problems as volunteer
      crops than do conventional crops. Glyphosate resistance transgenes have been
      found in fields of canola that are supposed to be non-transgenic. Under some
      circumstances, the largest risk of GRCs may be transgene flow (introgression)
      from GRCs to related species that might become problems in natural ecosystems.
      Glyphosate resistance transgenes themselves are highly unlikely to be a risk in
      wild plant populations, but when linked to transgenes that may impart fitness
      benefits outside of agriculture (e.g., insect resistance), natural ecosystems
      could be affected. The development and use of failsafe introgression barriers in
      crops with such linked genes is needed.

PMID- 16899737
TI  - Dependence of ammonia emissions from housing on the time cattle spent inside.
AB  - Buildings housing cattle contribute 19% (42 kt NH3-N yr(-1)) of total UK ammonia
      (NH3) emissions. In the UK there is not usually an abrupt switch from cattle
      being kept inside to when they are turned out to graze 24 h a day. Moreover,
      during the summer dairy cows return to the farm twice a day to be milked and may
      spend some time inside buildings. Hence, there is uncertainty over the treatment
      of the transitional and summer periods when inventorying NH3 emissions. The aim
      of this study was to measure, under controlled and replicated conditions, the
      relationship between the number of hours cattle spend in buildings and the NH3
      emissions from those buildings. Our results indicate that NH3 emissions decrease
      as the proportion of the day cattle spend in the buildings decreases, although
      the trend is not linear. Daily emission rates from cattle housed for 2 h ranged
      from 1.6 to 6.2 g NH3-N lu(-1) whereas emissions from cattle housed for 24 h
      ranged from 8.1 to 24.1 g NH3-N lu(-1). To significantly reduce NH3 emissions in
      comparison to those from buildings where cattle are housed for 24 h, the
      occupancy would have to be reduced to no more than 6 h each day. Thus, the
      strategy of extending the grazing season by allowing cattle to graze for c. 4 to
      12 h during the winter is unlikely to reduce NH3 emissions from buildings or
      overall.

PMID- 16899738
TI  - Bias of Tedlar bags in the measurement of agricultural odorants.
AB  - Odor regulations typically specify the use of dynamic dilution olfactometery
      (DDO) as a method to quantify odor emissions, and Tedlar bags are the preferred
      holding container for grab samples. This study was conducted to determine if
      Tedlar bags affect the integrity of sampled air from animal operations. Air
      samples were collected simultaneously in both Tedlar bags and Tenax thermal
      desorption tubes. Sample sources originated from either a hydrocarbon-free air
      tank, dynamic headspace chamber (DHC), or swine-production facility, and were
      analyzed by gas chromatography-mass spectrometry-olfactometry (GC-MS-O). Several
      background contaminants were identified from Tedlar bags, which included the
      odorous compounds N,N-dimethyl acetamide (DMAC), acetic acid, and phenol. Samples
      from the DHC demonstrated that recovery of malodor compounds was dependent on
      residence time in the Tedlar bag with longer residence time leading to lower
      recovery. After 24 h of storage, recovery of C3-C6 volatile fatty acids (VFA)
      averaged 64%, 4-methylphenol and 4-ethylphenol averaged 10%, and indole and 3
      methylindole were below the detection limits of GC-MS-O. The odor activity value
      (OAV) of grab samples collected in Tedlar bags were 33 to 65% lower following 24
      h of storage. These results indicate that significant odorant bias occurs when
      using Tedlar bags for the sampling of odors from animal production facilities.

PMID- 16899739
TI  - Nitrous oxide fluxes in turfgrass: effects of nitrogen fertilization rates and
      types.
AB  - Urban ecosystems are rapidly expanding and their effects on atmospheric nitrous
      oxide (N2O) inventories are unknown. Our objectives were to: (i) measure the
      magnitude, seasonal patterns, and annual emissions of N2O in turfgrass; (ii)
      evaluate effects of fertilization with a high and low rate of urea N; and (iii)
      evaluate effects of urea and ammonium sulfate on N2O emissions in turfgrass.
      Nitrogen fertilizers were applied to turfgrass: (i) urea, high rate (UH; 250 kg N
      ha(-1) yr(-1)); (ii) urea, low rate (UL; 50 kg N ha(-1) yr(-1)); and (iii)
      ammonium sulfate, high rate (AS; 250 kg N ha(-1) y(-1)); high N rates were
      applied in five split applications. Soil fluxes of N2O were measured weekly for 1
      yr using static surface chambers and analyzing N2O by gas chromatography. Fluxes
      of N2O ranged from -22 microg N2O-N m(-2) h(-1) during winter to 407 microg N2O-N
      m(-2) h(-1) after fall fertilization. Nitrogen fertilization increased N2O
      emissions by up to 15 times within 3 d, although the amount of increase differed
      after each fertilization. Increases were greater when significant precipitation
      occurred within 3 d after fertilization. Cumulative annual emissions of N2O-N
      were 1.65 kg ha(-1) in UH, 1.60 kg ha(-1) in AS, and 1.01 kg ha(-1) in UL. Thus,
      annual N2O emissions increased 63% in turfgrass fertilized at the high compared
      with the low rate of urea, but no significant effects were observed between the
      two fertilizer types. Results suggest that N fertilization rates may be managed
      to mitigate N2O emissions in turfgrass ecosystems.

PMID- 16899740
TI  - Assessment of the sulfur hexafluoride (SF6) tracer technique for measuring
      enteric methane emissions from cattle.
AB  - A commonly used method of measuring enteric methane (CH4) emissions from
      ruminants is the SF6 tracer technique that measures respired and eructated CH4.
      However, within the animal, a small proportion of CH4 is produced post-ruminally
      and some of this may escape through the rectum. The comparison of emissions using
      a chamber technique that measures all enteric CH4 losses, and the SF6 tracer
      technique, could give some insight into the magnitude of post-ruminal emission.
      The objective of our study was to assess the precision and accuracy of the SF6
      tracer technique against a chamber technique for cattle fed a range of diets.
      Using a repeated-measures design, eight beef heifers were offered a high grain or
      high forage diet for ad libitum or restricted (65% of ad libitum) feed intake to
      vary the site of digestion within the gastrointestinal tract (n = 24). The SF6
      tracer technique underestimated CH4 emissions on average by 4% relative to the
      chamber technique. This difference was not significant (P > 0.05) and suggests
      low post-ruminal CH4 emissions. There was a trend for greater accuracy and
      precision of the SF6 tracer technique when used with cattle fed a high forage
      diet at a restricted level of intake. The high forage diet corresponds to the
      conditions of cattle grazing pasture, suggesting the SF6 tracer technique is most
      reliable for the grazing system.

PMID- 16899741
TI  - Transport of coliphage in the presence and absence of manure suspension.
AB  - Mechanisms of coliphage transport and fate in the presence and absence of manure
      suspension were studied in saturated column experiments. In the presence of
      manure suspension, little inactivation of indigenous somatic coliphage occurred
      and the transport was controlled by deposition. The deposition followed a power
      law distribution with depth, and the magnitude increased with decreasing sand
      size. Comparison of the cumulative size distribution of manure components in the
      suspension initially and after passage through sand, suggested that particles
      retained by mechanical filtration and/or straining decreased the effective pore
      size and potentially induced straining of the somatic coliphage. A 2-site kinetic
      deposition model was used to estimate the magnitudes of attachment and straining
      in the presence of manure suspension, and provided a good description of the
      data. Modeling results indicated that straining accounted for 16 to 42% of the
      deposited somatic coliphage, and that both straining and attachment increased
      with decreasing sand size due to smaller pores and higher surface area,
      respectively. In the absence of manure suspension, phiX174 (a representative
      somatic coliphage) and MS2 (a male-specific RNA coliphage) transport was
      controlled by inactivation induced by the solid phase. This conclusion was based
      on comparison of coliphage transport behavior at 5 and 20 degrees C, mass balance
      information, and numerical modeling. Comparison of somatic coliphage transport
      data in the presence and absence of manure suspension revealed much higher
      effluent concentrations in the presence of manure. This difference was attributed
      to lower inactivation and higher detachment rates. The observed coliphage
      transport behavior suggests that survival of viruses may be extended in the
      presence of manure suspensions, and that transport studies conducted in the
      absence of manure suspension may not accurately characterize the transport
      potential of viruses in manure-contaminated environments.

PMID- 16899742
TI  - Modeling the environmental fate of cadmium in a large wastewater irrigation area.
AB  - The fate of cadmium in soils is governed by spatially heterogeneous processes
      that proceed from decades to centuries. This study aimed at modeling the fate of
      Cd within the wastewater irrigation area (WIA) of Braunschweig (Germany). The
      sandy soils (mainly Dystric Cambisol or Typic Haplumbrept) at this site (28 km2)
      have received considerable loads of heavy metals by irrigation of municipal
      wastewater for up to 40 yr. The soils of the WIA are in agricultural use. The
      main crops are sugar beet (Beta vulgaris L.), potato (Solanum tuberosum L.), and
      wheat (Triticum aestivum L.). As a result of asparagus (Asparagus officinalis L.)
      cropping, about 15% of the soils have been converted to Rigosols. In 1996, we
      measured the vertical distribution (0 to 1.2 m) of soil pH, organic carbon
      content, and the EDTA-extractable content and the solution phase concentration of
      Cd at 153 sites. At sites not used for asparagus cultivation, Cd has migrated on
      average to a depth of about 0.5 m. Due to deep plowing, which accelerates
      migration, Cd has been displaced on average to about 0.7 m at the Rigosol sites.
      To model the fate of Cd at the scale of the WIA, we used different parallel soil
      column approaches. In each column the local model SEFAH was used to simulate both
      displacement and plant uptake of Cd. The model was fed with measured or randomly
      generated soil data. The results of retrospective simulations from 1957 to 1996
      agreed well with observed Cd profiles. The better the spatial variability of
      sorption was described, the better the performance. Our simulation results show
      that Cd pollution of soil at first affects the soil-plant pathway. The
      breakthrough of Cd to the groundwater is dampened and is delayed for many
      decades.

PMID- 16899743
TI  - Distribution of uranium contamination in weathered fractured saprolite/shale and
      ground water.
AB  - The objective of this study was to determine how structure, stratigraphy, and
      weathering influence fate and transport of contaminants (particularly U) in the
      ground water and geologic material at the Department of Energy (DOE)
      Environmental Remediation Sciences Department (ERSD) Field Research Center (FRC).
      Several cores were collected near four former unlined adjoining waste disposal
      ponds. The cores were collected, described, analyzed for U, and compared with
      ground water geochemistry from surrounding multilevel wells. At some locations,
      acidic U-contaminated ground water was found to preferentially flow in small
      remnant fractures weathering the surrounding shale (nitric acid extractable U
      [U(NA)] usually < 50 mg kg(-1)) into thin (<25 cm) Fe oxide-rich clayey seams
      that retain U (U(NA) 239 to 375 mg kg(-1)). However, greatest contaminant
      transport occurs in a 2 to 3 m thick more permeable stratigraphic transition zone
      located between two less permeable, and generally less contaminated zones
      consisting of (i) overlying unconsolidated saprolite (U(NA) < 0.01 to 200 mg kg(
      1)) and (ii) underlying less-weathered bedrock (U(NA) generally < 0.01 to 7 mg
      kg(-1)). In this transition zone, acidic (pH < 4) U-enriched ground water (U of
      38 mg L(-1)) has weathered away calcite veins resulting in greater porosity,
      higher hydraulic conductivity, and higher U contamination (U(NA) 106 to 745 mg
      kg(-1)) of the weathered interbedded shale and sandstone. These characteristics
      of the transition zone produce an interval with a high flux of contaminants that
      could be targeted for remediation.

PMID- 16899744
TI  - Physicochemical and mineralogical characterization of soil-saprolite cores from a
      field research site, Tennessee.
AB  - Site characterization is an essential initial step in determining the feasibility
      of remedial alternatives at hazardous waste sites. Physicochemical and
      mineralogical characterization of U-contaminated soils in deeply weathered
      saprolite at Area 2 of the DOE Field Research Center (FRC) site, Oak Ridge, TN,
      was accomplished to examine the feasibility of bioremediation. Concentrations of
      U in soil-saprolite (up to 291 mg kg(-1) in oxalate-extractable U(o)) were
      closely related to low pH (ca. 4-5), high effective cation exchange capacity
      without Ca (64.7-83.2 cmol(c) kg(-1)), amorphous Mn content (up to 9910 mg kg(
      1)), and the decreased presence of relative clay mineral contents in the bulk
      samples (i.e., illite 2.5-12 wt. %, average 32 wt. %). The pH of the fill
      material ranged from 7.0 to 10.5, whereas the pH of the saprolite ranged from 4.5
      to 8. Uranium concentration was highest (about 300 mg kg(-1)) at around 6 m below
      land surface near the saprolite-fill interface. The pH of ground water at Area 2
      tended to be between 6 and 7 with U concentrations of about 0.9 to 1.7 mg L(-1).
      These site specific characteristics of Area 2, which has lower U and nitrate
      contamination levels and more neutral ground water pH compared with FRC Areas 1
      and 3 (ca. 5.5 and <4, respectively), indicate that with appropriate addition of
      electron donors and nutrients bioremediation of U by metal reducing
      microorganisms may be possible.

PMID- 16899745
TI  - Nitrogen loads through baseflow, stormflow, and underflow to Rehoboth Bay,
      Delaware.
AB  - A detailed study of water and nitrogen (N) discharge from a small, representative
      subwatershed of Rehoboth Bay, Delaware, was conducted to determine total N loads
      to the bay. The concentrations of ammonium (NH4(+)), nitrate + nitrite (NO3(-) +
      NO2(-)), and dissolved and particulate organic N were determined in baseflow and
      storm waters discharging from Bundicks Branch from October 1998 to April 2002. A
      novel hydrographic separation model that accounts for significant decreases in
      baseflow during storm events was developed to estimate N loads during unsampled
      storms. Nitrogen loads based on gauged flows alone (7100-19,100 kg/yr)
      significantly underestimated those based on land use-land cover (LULC) and
      estimated N export factors from different classes of LULC (32,000-40,600 kg/yr).
      However, when ungauged underflow and associated N loads were included in the
      total loads (25,500-33,800 kg/yr), there was much better agreement with LULC
      export models. This suggests that in permeable coastal plain sediments, underflow
      contributes significantly to N fluxes to estuarine receiving waters, particularly
      in drier years. Based on the similarity in LULC, N loads from the Bundicks Branch
      subwatershed were used to estimate upland loads to the entire Rehoboth Bay
      Watershed (259,000-316,000 kg/yr). These N loads from the watershed were much
      greater than those from direct atmospheric deposition (49,000-64,500 kg/yr) and
      from a local wastewater treatment plant (9700-13,700 kg/yr). While the watershed
      was the principal source of N at all times during the year, the relative
      contributions from the watershed, wastewater, and direct atmospheric deposition
      varied predictably with season.

PMID- 16899746
TI  - Use of beryllium-7 to document soil redistribution following forest harvest
      operations.
AB  - Rapid and reliable methods for documenting soil erosion associated with forest
      harvest operations are needed to support the development of best management
      practices for soil and water conservation. To address this need, the potential
      for using 7Be measurements to estimate patterns and amounts of soil
      redistribution associated with individual post-harvest events was explored. The
      7Be technique, which was originally developed for use on agricultural land, was
      employed to estimate soil redistribution associated with a period of heavy
      rainfall within a harvested forest area located in the Lake Region of Chile (39
      degrees 44'7'' S, 73 degrees 10'39'' W; 22% slope; and mean annual rainfall 2300
      mm yr(-1)). The results provided by the 7Be technique were validated against
      direct measurements of soil gain or loss during the same period obtained using
      erosion pins. The information produced by the two approaches was similar. The
      results of this study demonstrate the potential for using 7Be measurements to
      document event-based erosion in recently harvested forest areas.

PMID- 16899747
TI  - Impact of land drainage on peatland hydrology.
AB  - There is a long history of drainage of blanket peat but few studies of the long
      term hydrological impact of drainage. This paper aims to test differences in
      runoff production processes between intact and drained blanket peat catchments
      and determine whether there have been any long-term changes in stream flow since
      drainage occurred. Hillslope runoff processes and stream discharge were measured
      in four blanket peat catchments. Two catchments were drained with open-cut
      ditches in the 1950s. Ditching originally resulted in shorter lag times and
      flashier storm hydrographs but no change in the annual catchment runoff
      efficiency. In the period between 2002 and 2004, the hydrographs in the drained
      catchments, while still flashy, were less sensitive to rainfall than in the 1950s
      and the runoff efficiency had significantly increased. Drains resulted in a
      distinctive spatial pattern of runoff production across the slopes. Overland flow
      was significantly lower in the drained catchments where throughflow was more
      dominant. In the intact peatlands, matrix throughflow produced by peat layers
      below 10 cm was rare and produced <1% of the runoff. However, in drained
      peatlands, matrix throughflow in deeper peat layers was common and provided
      around 23% of the runoff from gauged plots. Macropore flow, the density of soil
      piping, and pipeflow were significantly greater in drained peatlands than in
      intact basins. Gradual changes to peat structure could explain the long-term
      changes in river flow, which are in addition to those occurring in the immediate
      aftermath of peatland drainage.

PMID- 16899748
TI  - Sorption-desorption of carbamazepine from irrigated soils.
AB  - Th anti-seizure medication carbamazepine is often found in treated sewage
      effluent and environmental samples. Carbamazepine has been shown to be very
      persistent in sewage treatment, as well as ground water. Due to environmental
      persistence, irrigation with sewage effluent could result in carbamazepine
      contamination of surface and ground water. To determine the potential for
      leaching of carbamazepine, a series of adsorption and desorption batch
      equilibrium experiments were conducted on irrigated soils. It was found that
      carbamazepine adsorption to biosolid-amended (T) soils had a KD of 19.8 vs. 12.6
      for unamended soil. Based on adsorption, carbamazepine leaching potential would
      be categorized as low. During desorption significant hysteresis was observed and
      KD increased for both soils. Desorption isotherms also indicate a potential for
      irreversibly bound carbamazepine in the T soil. Results indicate that initial
      removal of carbamazepine via adsorption from irrigation water is significant and
      that desorption characteristics would further limit the mobility of carbamazepine
      through the soil profile indicating that carbamazepine found in sewage effluent
      used for irrigation has a low leaching potential.

PMID- 16899749
TI  - Land application of carbonatic lake-dredged materials: effects on soil quality
      and forage productivity.
AB  - The ability to reuse carbonatic lake-dredged materials (CLDM) for agricultural
      purposes is important because it reduces offshore disposal and provides an
      alternative to disposal of the materials in landfills that are already overtaxed.
      A four-year (2001 to 2005) study on land application of CLDM as an option for
      disposal was conducted on a beef cattle pasture in south central Florida. The
      objectives of this study were (i) to assess CLDM as a soil amendment to improve
      quality of sandy soils in most subtropical beef cattle pastures and (ii) to
      determine the effect of CLDM on productivity and nutritive values of bahiagrass
      (BG, Paspalum notatum Flugge) in subtropical beef cattle pasture. The five
      treatment combinations arranged in randomized complete block design were
      represented by plots with different ratios (R) of natural soil (NS) to CLDM: R1
      (1000 g kg(-1):0 g kg(-1)); R2 (750 g kg(-1):250 g kg(-1)); R3 (500 g kg(-1):500
      g kg(-1)); R4 (250 g kg(-1):750 g kg(-1)); and R5 (0 g kg(-1):1000 g kg(-1)).
      Addition of CLDM had significant (p < or = 0.001) effects on soil quality and
      favorable influence on forage establishment and nutritive values. Compared with
      the control plots (0 g kg(-1)), the soils in plots amended with CLDM exhibited
      (i) lower penetration resistance, (ii) an increase in soil pH and exchangeable
      cations (Ca and Mg), and (iii) decrease in the levels of soil trace metals (Mn,
      Cu, Fe, Zn, and Si). Results disclosed consistently and significantly (p < or =
      0.001) higher BG biomass production (forage yield = -106.3x(2) + 1015.8x - 39.2;
      R(2) = 0.99**) and crude protein content (CP = 1.24x + 6.48; R(2) = 0.94**) from
      plots amended with CLDM than those of BG planted on plots with no CLDM treatment.

PMID- 16899750
TI  - Sorption and degradation of pesticides in nursery recycling ponds.
AB  - Knowledge of pesticide distribution and persistence in nursery recycling pond
      water and sediment is critical for preventing phytotoxicity of pesticides during
      water reuse and to assess their impacts to the environment. In this study,
      sorption and degradation of four commonly used pesticides (diazinon,
      chlorpyrifos, chlorothalonil, and pendimethalin) in sediments from two nursery
      recycling ponds was investigated. Results showed that diazinon and chlorothalonil
      were moderately sorbed [K(OC) (soil organic carbon distribution coefficient) from
      732 to 2.45 x 10(3) mL g(-1)] to the sediments, and their sorption was mainly
      attributable to organic matter content, whereas chlorpyrifos and pendimethalin
      were strongly sorbed (K(OC) > or = 7.43 x 10(3) mL g(-1)) to the sediments, and
      their sorption was related to both organic matter content and sediment texture.
      The persistence of diazinon and chlorpyrifos was moderate under aerobic
      conditions (half-lives = 8 to 32 d), and increased under anaerobic conditions
      (half-lives = 12 to 53 d). In contrast, chlorothalonil and pendimethalin were
      quickly degraded under aerobic conditions with half-lives < 2.8 d, and their
      degradation was further enhanced under anaerobic conditions (half-lives < 1.9 d).
      The strong sorption of chlorpyrifos and pendimethalin by the sediments suggests
      that the practice of recycling nursery runoff would effectively retain these
      compounds in the recycling pond, minimizing their offsite movement. The prolonged
      persistence of diazinon and chlorpyrifos, however, implies that incidental
      spills, such as overflows caused by storm events, may contribute significant
      loads of such pesticides into downstream surface water bodies.

PMID- 16899751
TI  - Leaching and crop uptake of nitrogen and phosphorus from pig slurry as affected
      by different application rates.
AB  - The influence of increasing pig slurry applications on leaching and crop uptake
      of N and P by cereals was evaluated in a 3-yr study of lysimeters filled with a
      sandy soil. The slurry was applied at N rates of 50 (S50), 100 (S100), 150
      (S150), and 200 (S200) kg ha(-1) during 2 of the 3 yr. The P rates applied with
      slurry were: 40 (S50), 80 (S100), 120 (S150), and 160 (S200) kg ha(-1) yr(-1).
      Simultaneously, NH4NO3 and Ca(H2PO4)2 were applied at rates of 100 kg N ha(-1)
      and 50 kg P ha(-1), respectively, to additional lysimeters (F100), while others
      were left unfertilized (F0). During the 3-yr period, the leaching load of total N
      tended to increase with increasing slurry application to, on average, 139 kg ha(
      1) at the highest application rate (S200). The corresponding N leaching loads (kg
      ha(-1)) in the other treatments were: 75 (F0), 103 (F100), 93 (S50), 120 (S100),
      and 128 (S150). The loads of slurry-derived N in the S100, S150, and S200
      treatments were significantly larger (P < 0.05) than those of fertilizer-derived
      N. In contrast, P leaching tended to decrease with increasing input of slurry,
      and it was lower in all treatments that received P at or above 50 kg P ha(-1) yr(
      1) with slurry or fertilizer than in the unfertilized treatment. The crop use
      efficiency of added N and P was clearly higher when NH4NO3 and Ca(H2PO4)2 were
      used rather than slurry (60 vs. 35% for N, 38 vs. 6-9% for P), irrespective of
      slurry application rate. Therefore, from both a production and water quality
      point of view, inorganic fertilizers seem to have environmental benefits over pig
      slurry when used on sandy soils.

PMID- 16899752
TI  - Is dew water potable? Chemical and biological analyses of dew water in Ajaccio
      (Corsica Island, France).
AB  - To determine to what extent dew water is potable without further treatment, a
      thorough set of chemical and biological analyses were performed on 10 samples of
      dew water collected on a large scale radiative collector (29.83 m2) in Ajaccio
      (Corsica Island, France), between 21 May 2002 and 5 Mar. 2003. Samples were
      collected following four protocols according to the dew volume amount and 48
      parameters (ions, minerals, and bacteria) were analyzed and compared to French
      and European Union legislation and also World Health Organization (WHO)
      recommendations. Aluminum and Fe were the main pollutants whose concentrations
      were significantly larger than recommended. Their presence is due to local
      deposition of aerosols coming from the Sahara (a characteristic of the
      Mediterranean basin). A large number of biologically cultivable microorganisms
      were found, together with bacteria typical of fecal contamination. For dew water
      to be potable with respect to present legislation at the Ajaccio site, it should
      be disinfected and treated for turbidity.

PMID- 16899753
TI  - Change in soluble phosphorus in soils following fertilization is dependent on
      initial Mehlich-3 phosphorus.
AB  - There is a lack of information on how fertilization and initial Mehlich-3
      phosphorus (M3P) interact to affect water soluble P (WSP) in soils. Our
      objectives were to (i) quantify the relationship between WSP and M3P for four
      textural diverse benchmark soils of North Carolina (NC) and (ii) quantify the
      change in WSP concentrations following P additions to soils over a wide range of
      initial M3P. Soils known to represent a wide range in M3P were collected from an
      Autryville loamy sand (loamy, siliceous, subactive, thermic Arenic Paleudults),
      Wasda muck (fine-loamy, mixed, semiactive, acid, thermic Histic Humaquepts),
      Georgeville silt loam (fine, kaolinitic, thermic Typic Kanhapludults), and
      Pacolet sandy clay loam (fine, kaolinitic, thermic Typic Kanhapludults) and
      analyzed for M3P, Fe, Al, and WSP. An incubation study was also conducted where
      four samples representing a range in M3P from each series were fertilized at
      rates of 150 and 300 kg P ha(-1), and WSP was measured at 1, 7, and 21 d after
      fertilization. The Wasda muck exhibited a change point at 115 mg P kg(-1) across
      a broad range of M3P concentrations (60-238 mg kg(-1)) while Autryville,
      Georgeville, and Pacolet series (with ranges in M3P of 32-328, 119-524, 0-1034 mg
      P kg(-1), respectively) maintained linear relationships between WSP and M3P. For
      the fertilized soils, significant increases in WSP occurred regardless of P rate.
      Yet, WSP concentrations were greater in soils with greater initial M3P. Thus,
      these data suggest that shifting animal waste applications to fields of
      relatively lower M3P concentrations would have an immediate impact on reducing
      risk for P losses, if all other factors are equal.

PMID- 16899754
TI  - Preferential flow estimates to an agricultural tile drain with implications for
      glyphosate transport.
AB  - Agricultural subsurface drains, commonly referred to as tile drains, are
      potentially significant pathways for the movement of fertilizers and pesticides
      to streams and ditches in much of the Midwest. Preferential flow in the
      unsaturated zone provides a route for water and solutes to bypass the soil matrix
      and reach tile drains faster than predicted by traditional displacement theory.
      This paper uses chloride concentrations to estimate preferential flow
      contributions to a tile drain during two storms in May 2004. Chloride, a
      conservative anion, was selected as the tracer because of differences in chloride
      concentrations between the two sources of water to the tile drain, preferential
      and matrix flow. A strong correlation between specific conductance and chloride
      concentration provided a mechanism to estimate chloride concentrations in the
      tile drain throughout the storm hydrographs. A simple mixing analysis was used to
      identify the preferential flow component of the storm hydrograph. During two
      storms, preferential flow contributed 11 and 51% of total storm tile drain flow;
      the peak contributions, 40 and 81%, coincided with the peak tile drain flow.
      Positive relations between glyphosate [N-(phosphonomethyl)glycine] concentrations
      and preferential flow for the two storms suggest that preferential flow is an
      important transport pathway to the tile drain.

PMID- 16899755
TI  - Sorption of inorganic and total phosphorus from dairy and swine slurries to soil.
AB  - Understanding P sorption from animal manures is essential to formulate best
      management practices with regard to land application of manure from the
      standpoint of crop production and environmental quality. Little research has
      focused on the construction of P sorption isotherms where the P source is manure.
      The objectives of this study were to: (i) develop a procedure to characterize how
      inorganic P (P(i)) and total P (P(t)) from dairy slurry and swine slurry sorbs to
      soil; and (ii) compare the sorption characteristics of P(i) and P(t) where the P
      source was dairy slurry, swine slurry, or potassium phosphate (KH2PO4). Sorption
      solutions were prepared in 0.1 M KCl at pH 6 and equilibrated with soils at a
      1:25 (w/v) soil/solution ratio for 24 h. Inorganic P, P(t), Al, and Fe in the
      equilibrated solutions were measured. For all soils, P(i) and P(t) sorption
      capacity of dairy slurry was greater than KH2PO4. Total P sorption capacity of
      swine slurry was greater than KH2PO4, while P(i) sorption capacity was less than
      KH2PO4. Overall, P(i) and P(t) sorption strengths of the manure slurries were
      less than or equal to KH2PO4. Increased P(i) sorption from dairy slurry was
      correlated with Fe and Al desorption. Reduction of P(i) sorption capacity from
      swine slurry was related to preferential sorption of organic P. Additional
      studies need to be conducted to determine how differences in P sorption between
      manures and fertilizer impact in-field P availability to a crop and potential for
      losses in runoff water.

PMID- 16899756
TI  - Fresh, stockpiled, and composted beef cattle feedlot manure: nutrient levels and
      mass balance estimates in Alberta and Manitoba.
AB  - The fate of manure nutrients in beef cattle (Bos taurus) feedlots is influenced
      by handling treatment, yet few data are available in western Canada comparing
      traditional practices (fresh handling, stockpiling) with newer ones (composting).
      This study examined the influence of handling treatment (fresh, stockpiled, or
      composted) on nutrient levels and mass balance estimates of feedlot manure at
      Lethbridge, Alberta, and Brandon, Manitoba. Total carbon (TC) concentration of
      compost (161 kg Mg(-1)) was lower (P < 0.001) than stockpiled (248 kg Mg(-1)),
      which was in turn lower (P < 0.001) than fresh manure (314 kg Mg(-1)). Total
      nitrogen (TN) concentration was not affected by handling treatment while total
      phosphorus (TP) concentration increased with composting at Lethbridge. The
      percent inorganic nitrogen (PIN) was lower (P < 0.01) for compost (5.1%) than
      both fresh (24.7%) and stockpiled (28.9%) manure. Composting led to higher (P <
      0.05) dry matter (DM) losses (39.8%) compared to stockpiling (22.5%) and higher
      (P < 0.05) total mass (water + DM) losses (65.6 vs. 35.2%). Carbon (C) losses
      were higher (P < 0.01) with composting (66.9% of initial) than with stockpiling
      (37.5%), as were nitrogen (N) losses (46.3 vs. 22.5%, P < 0.05). Composting
      allowed transport of two times as much P as fresh manure and 1.4 times as much P
      as stockpiled manure (P < 0.001) on an "as is" basis. Our study looked at one
      aspect of manure management (i.e., handling treatment effects on nutrient
      concentrations and mass balance estimates) and, as such, should be viewed as one
      component in the larger context of a life cycle assessment.

PMID- 16899757
TI  - Sorption dynamics of organic and inorganic phosphorus compounds in soil.
AB  - Phosphorus retention in soils is influenced by the form of P added. The potential
      impact of one P compound on the sorption of other P compounds in soils has not
      been widely reported. Sorption isotherms were utilized to quantify P retention by
      benchmark soils from Indiana, Missouri, and North Carolina when P was added as
      inorganic P (Pi) or organic P (beta-D-glucose-6-phosphate, G6P; adenosine 5'
      triphosphate, ATP; and myoinositol hexaphosphate, IP6) and to determine whether
      soil P sorption by these organic P compounds and Pi was competitive. Isotherm
      supernatants were analyzed for pH and total P using standard protocols, while Pi
      and organic P compounds were assayed using ion chromatography. Under the
      controlled conditions of this study, the affinity of all soils for P sources
      followed the order IP6 > G6P > ATP > Pi. Each organic P source had a different
      potential to desorb Pi from soils, and the order of greatest to least Pi
      desorption was G6P > ATP > IP6. Glucose-6-phosphate and ATP competed more
      directly with Pi for sorption sites than IP6 at greater rates of P addition, but
      at the lesser rates of P addition, IP6 actually desorbed more Pi. Inositol
      hexaphosphate was strongly sorbed by all three soils and was relatively
      unaffected by the presence of other P sources. Decreased total P sorption due to
      desorption of Pi can be caused by relatively small additions of organic P, which
      may help explain vertical P movement in manured soils. Sorption isotherms
      performed using Pi alone did not accurately predict total P sorption in soils.

PMID- 16899758
TI  - The skeletal muscle satellite cell: the stem cell that came in from the cold.
AB  - The muscle satellite cell was first described and actually named on the basis of
      its anatomic location under the basement membrane surrounding each myofiber. For
      many years following its discovery, electron microscopy provided the only
      definitive method of identification. More recently, several molecular markers
      have been described that can be used to detect satellite cells, making them more
      accessible for study at the light microscope level. Satellite cells supply
      myonuclei to growing myofibers before becoming mitotically quiescent in muscle as
      it matures. They are then activated from this quiescent state to fulfill their
      roles in routine maintenance, hypertrophy, and repair of adult muscle. Because
      muscle is able to efficiently regenerate after repeated bouts of damage, systems
      must be in place to maintain a viable satellite cell pool, and it was proposed
      over 30 years ago that self-renewal was the primary mechanism. Self-renewal
      entails either a stochastic event or an asymmetrical cell division, where one
      daughter cell is committed to differentiation whereas the second continues to
      proliferate or becomes quiescent. This classic model of satellite cell self
      renewal and the importance of satellite cells in muscle maintenance and repair
      have been challenged during the past few years as bone marrow-derived cells and
      various intramuscular populations were shown to be able to contribute myonuclei
      and occupy the satellite cell niche. This is a fast-moving and dynamic field,
      however, and in this review we discuss the evidence that we think puts this
      enigmatic cell firmly back at the center of adult myogenesis.

PMID- 16899759
TI  - A novel method for multiple labeling combining in situ hybridization with
      immunofluorescence.
AB  - In situ hybridization (ISH) is a particularly useful method to investigate de
      novo mRNA expression in tissue sections. High specificity and sensitivity of this
      technique combined with the great preservation of tissue and cellular morphology
      conferred by fixatives such as 4% paraformaldehyde, pH 9.5, make ISH a tool of
      choice for detecting genes of interest in individual cells in the central nervous
      system (CNS). Here we describe a novel method that combines radioactive ISH with
      immunofluorescence on the same tissue section to identify cell populations
      expressing selected mRNA transcripts. This novel method has several major
      advantages over previously described double-labeling light microscopic methods
      combining enzymatic immunohistochemistry and ISH including (1) complete
      protection against loss of hybridization signal that normally occurs during the
      immunoenzymatic reaction, (2) improved immunolabeling sensitivity due to the
      proteinase K digestion step during ISH, (3) detection of several proteins
      specific for different cell populations on the same tissue section, and (4)
      counterstaining of tissue sections without affecting visualization of
      immunolabeling. This new method will be particularly useful for investigators
      looking to identify cell populations producing mRNAs expressed in low abundance
      such as cytokines, chemokines, and growth factors in the intact and/or injured
      mammalian CNS.

PMID- 16899761
TI  - Prolonged exposure to hyperoxia increases perivascular mast cells in rat lungs.
AB  - Prolonged hyperoxia, as may be used to treat patients with severe hypoxemia, can
      lead to lung injury, respiratory failure, and death. Resident mast cells play
      important roles in regulating the lung response to changing environmental
      conditions, as evidenced by their roles in asthma and airway hyperresponsiveness.
      In this study we evaluated the effect of prolonged hyperoxia on the number and
      distribution of mast cells in the rat lung. In rats maintained in normoxia, mast
      cells were distributed primarily in the loose connective tissue surrounding large
      bronchioles and vessels of the lung. In rats exposed to normobaric hyperoxia for
      72 hr, mast cell number in lung sections increased significantly, and mast cells
      were found preferentially accumulated around vessels throughout the lung.
      Notably, mast cells around smaller vessels were abundant in hyperoxic lungs but
      rare in normoxic lungs. Also, mast cells were increased in the pleura of lungs
      exposed to hyperoxia. These changes in mast cell number and distribution in
      response to hyperoxia were evident in aged (22-month-old) rats as well as young
      (3-month-old) rats. As mast cell-derived mediators have many effects, e.g., on
      vascular leak and vascular tone, positioning of increased mast cell numbers
      throughout the lung vasculature may be an important contributor to changes in
      lung function subsequent to persistent hyperoxia.

PMID- 16899763
TI  - An agarose matrix facilitates sectioning of tissue microarray blocks.
AB  - Tissue microarray (TMA) is a powerful, high-throughput technique for in situ
      investigation of biomarkers in many tissue samples in a paraffin block by
      immunohistochemistry or fluorescence in situ hybridization (FISH), and has
      rapidly become the standard in marker studies. One of the difficult steps in the
      procedure is the sectioning of array blocks and mounting of sections using
      special slides and/or adhesive-coated tape, which demands specific experience and
      is time-consuming. We report an arraying method that allows melting of the
      receiving paraffin block and subsequent sectioning like any ordinary paraffin
      embedded tissue block. The major difference from the standard microarray
      technique is the use of an agarose matrix in the recipient block. The agarose
      matrix allows melting of the paraffin without disturbing the array, resulting in
      perfect integration of the tissue cores. The agarose-paraffin TMA blocks limit
      tissue core loss during cutting, mounting, or immunohistochemical or FISH
      staining and better maintains the array.

PMID- 16899762
TI  - Depletion of alveolar glycogen corresponds with immunohistochemical development
      of CD208 antigen expression in perinatal lamb lung.
AB  - CD208 DC lysosomal-associated protein is a marker of activated human dendritic
      cells; however, recently it was described as a marker of adult type II
      pneumocytes in many species including humans and sheep. Our hypothesis was that
      CD208 is developmentally regulated in lung pneumocytes. Lamb lungs at varying
      stages of development were stained immunohistochemically for CD208 and with Nile
      red (a fluorescent stain for lamellar bodies of type II cells) along with
      pulmonary markers of maturation (glycogen stores and surfactant protein A [SP-A]
      expression) or proliferation (Ki-67). CD208 staining and Nile red were localized
      to rare pneumocytes in young fetal lambs (day 115), increasing in frequency and
      stain intensity with age. Periodic acid-Schiff staining of glycogen granules was
      most prominent in the young lambs (day 115) with reduced staining through
      advancing lung development. SP-A was detected in pulmonary epithelia and staining
      in alveoli increased through gestation with decreased staining at 2 weeks of age.
      Intranuclear Ki-67 staining decreased through late gestation but was increased in
      2-week-old lambs. Ontogeny of CD208 staining and depletion of glycogen were
      correlated (p<0.0001) and consistent with the premise that CD208 is localized to
      developing lamellar bodies. The findings suggest that CD208 antigen expression
      may serve as a marker for pneumocyte maturation in the developing fetal lung.

PMID- 16899760
TI  - Cytoglobin is a stress-responsive hemoprotein expressed in the developing and
      adult brain.
AB  - Cytoglobin (Cygb) is a novel tissue hemoprotein relatively similar to myoglobin
      (Mb). Because Cygb shares several structural features with Mb, we hypothesized
      that Cygb functions in the modulation of oxygen and nitric oxide metabolism or in
      scavenging free radicals within a cell. In the present study we examined the
      spatial and temporal expression pattern of Cygb during murine embryogenesis.
      Using in situ hybridization, RT-PCR, and Northern blot analyses, limited Cygb
      expression was observed during embryogenesis compared with Mb expression. Cygb
      expression was primarily restricted to the central nervous system and neural
      crest derivatives during the latter stages of development. In the adult mouse,
      Cygb is expressed in distinct regions of the brain as compared with neuroglobin
      (Ngb), another globin protein, and these regions are responsive to oxidative
      stress (i.e., hippocampus, thalamus, and hypothalamus). In contrast to Ngb, Cygb
      expression in the brain is induced in response to chronic hypoxia (10% oxygen).
      These results support the hypothesis that Cygb is an oxygen-responsive tissue
      hemoglobin expressed in distinct regions of thenormoxic and hypoxic brain and may
      play a key role in the response of the brain to ahypoxic insult.

PMID- 16899764
TI  - Snail-dependent and -independent epithelial-mesenchymal transition in oral
      squamous carcinoma cells.
AB  - Disappearance of E-cadherin is a milestone for epithelial-mesenchymal transition
      (EMT), found both in carcinomas and in some fibrotic diseases. We have studied
      the mechanisms of EMT in oral squamous cell carcinoma (SCC) cells isolated from
      primary tumor (43A) and its recurrent tumor (43B). Whereas the cells from primary
      carcinoma displayed a typical phenotype of squamous epithelial cells including E
      cadherin and laminin-332 (laminin-5), cells from recurrent tumor expressed
      characteristics of dedifferentiated, EMT-experienced tumors. 43B cells expressed
      E-cadherin repressors ZEB-1/deltaEF1 and especially ZEB-2/SIP1, which therefore
      appear as candidates for endogenous EMT in these cells. Differences between
      endogenous and exogenous EMT were assessed by transfecting 43A cells with SNAIL
      cDNA. SNAIL-transfected cells showed complete EMT phenotype with fibroblastoid
      appearance, vimentin filaments, E-cadherin/N-cadherin switch, lack of
      hemidesmosomes and, as a new feature of EMT, lack of laminin-332 synthesis.
      Upregulation of ZEB-1 and ZEB-2 was evident in these cells, suggesting that SNAIL
      can regulate these E-cadherin repressors. New monoclonal antibodies against SNAIL
      showed nuclear immunoreactivity not only in the SNAIL-transfected cells but also
      in carcinoma cells lacking production of Lm-332 and showing signs of EMT. These
      results suggest that changes in the epithelial cell differentiation program and
      EMT in SCC cells can result from the interplay among several E-cadherin
      repressors; however, SNAIL alone is able to accomplish a complete EMT.

PMID- 16899765
TI  - Immunohistochemical distribution of NGF, BDNF, NT-3, and NT-4 in adult rhesus
      monkey brains.
AB  - Immunohistochemical distribution and cellular localization of neurotrophins was
      investigated in adult monkey brains using antisera against nerve growth factor
      (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and
      neurotrophin-4 (NT-4). Western blot analysis showed that each antibody
      specifically recognized appropriate bands of approximately 14.7 kDa, 14.2 kDa,
      13.6 kDa, and 14.5 kDa, for NGF, BDNF, NT-3, and NT-4, respectively. These
      positions coincided with the molecular masses of the neurotrophins studied.
      Furthermore, sections exposed to primary antiserum preadsorbed with full-length
      NGF, BDNF, NT-3, and NT-4 exhibited no detectable immunoreactivity, demonstrating
      specificities of the antibodies against the tissues prepared from rhesus monkeys.
      The study provided a systematic report on the distribution of NGF, BDNF, NT-3,
      and NT-4 in the monkey brain. Varying intensity of immunostaining was observed in
      the somata and processes of a wide variety of neurons and glial cells in the
      cerebrum, cerebellum, hippocampus, and other regions of the brain. Neurons in
      some regions such as the cerebral cortex and the hippocampus, which stained for
      neurotrophins, also expressed neurotrophic factor mRNA. In some other brain
      regions, there was discrepancy of protein distribution and mRNA expression
      reported previously, indicating a retrograde or anterograde action mode of
      neurotrophins. Results of this study provide a morphological basis for the
      elucidation of the roles of NGF, BDNF, NT-3, and NT-4 in adult primate brains.

PMID- 16899766
TI  - Ethanol and cardiac function.

PMID- 16899767
TI  - Intracellular signal transduction for migration and actin remodeling in vascular
      smooth muscle cells after sphingosylphosphorylcholine stimulation.
AB  - Molecular mechanisms underlying migration of vascular smooth muscle cells (VSMCs)
      toward sphingosylphosphorylcholine (SPC) were analyzed in light of the hypothesis
      that remodeling of the actin cytoskeleton should be involved. After SPC
      stimulation, mitogen-activated protein kinases (MAPKs), including p38 MAPK (p38)
      and p42/44 MAPK (p42/44), were found to be phosphorylated. Migration of cells
      toward SPC was reduced in the presence of SB-203580, an inhibitor of p38, but not
      PD-98059, an inhibitor of p42/44. Pertussis toxin (PTX), a Gi protein inhibitor,
      induced an inhibitory effect on p38 phosphorylation and VSMC migration. Myosin
      light chain (MLC) phosphorylation occurred after SPC stimulation with or without
      pretreatment with SB-203580 or PTX. The MLC kinase inhibitor ML-7 and the Rho
      kinase inhibitor Y-27632 inhibited MLC phosphorylation but only partially
      inhibited SPC-directed migration. Complete inhibition was achieved with the
      addition of SB-203580. After SPC stimulation, the actin cytoskeleton formed thick
      bundles of actin filaments around the periphery of cells, and the cells were
      surrounded by elongated filopodia, i.e., magunapodia. The peripheral actin
      bundles consisted of alpha- and beta-actin, but magunapodia consisted exclusively
      of beta-actin. Such a remodeling of actin was reversed by addition of SB-203580
      and PTX, but not ML-7 or Y-27632. Taken together, our biochemical and
      morphological data confirmed the regulation of actin remodeling and suggest that
      VSMCs migrate toward SPC, not only by an MLC phosphorylation-dependent pathway,
      but also by an MLC phosphorylation-independent pathway.

PMID- 16899770
TI  - Images in clinical medicine. Adie's pupil in the Ross syndrome.

PMID- 16899768
TI  - Mechanisms of endothelial response to oxidative aggression: protective role of
      autologous VEGF and induction of VEGFR2 by H2O2.
AB  - The defense mechanisms of endothelial cells (EC) against reactive oxygen species
      (ROS) are insufficiently characterized. We have addressed the hypothesis that
      vascular endothelial growth factor (VEGF) and its receptors are relevant elements
      in this response. Cell viability, VEGF and VEGF receptor (VEGFR1 and VEGFR2)
      expression, and transcription factor activation were studied on transient
      exposure of monolayer EC to H2O2. Wild-type and mutant inhibitors of kappaBalpha
      (IkappaBalpha) constructions were used to further assess the role of NF-kappaB in
      the induction of VEGFR2 expression. A concentration of H2O2>or=60 microM elicited
      clear-cut damaging effects on EC, whereas lower concentrations (2-4 microM) were
      cytoprotective. The cytoprotective effect was shifted to an EC-damaging pattern
      by means of specific VEGF blockade, therefore revealing a major role of
      autologous VEGF. Exposure to H2O2 increased VEGF and VEGFR2 mRNA and protein in
      EC, without affecting VEGFR1 expression. Also, H2O2 challenge was accompanied by
      increased NF-kappaB, activator protein-1, and specific protein-1 nuclear binding.
      A role of NF-kappaB as the mediator of the H2O2 induction of VEGFR2 mRNA
      expression was supported by inhibition by the ROS scavenger pyrrolidine
      dithiocarbamate and by the blocking effect of transfected IkappaBalpha. Exposure
      to exogenous VEGF also increased VEGFR2 and induced NF-kappaB in EC. In summary,
      autologous VEGF is instrumental for EC protection induced by low concentrations
      of ROS. ROS induce expression not only of VEGF but also of VEGFR2. VEGFR2
      increase by ROS is mainly driven through a NF-kappaB-dependent pathway.

PMID- 16899771
TI  - Preimplantation diagnosis for genetic susceptibility.

PMID- 16899772
TI  - Genes on the Web--direct-to-consumer marketing of genetic testing.

PMID- 16899773
TI  - DNA testing, banking, and genetic privacy.

PMID- 16899774
TI  - Turning the page at the CMAJ.

PMID- 16899775
TI  - High-dose atorvastatin after stroke or transient ischemic attack.
AB  - BACKGROUND: Statins reduce the incidence of strokes among patients at increased
      risk for cardiovascular disease; whether they reduce the risk of stroke after a
      recent stroke or transient ischemic attack (TIA) remains to be established.
      METHODS: We randomly assigned 4731 patients who had had a stroke or TIA within
      one to six months before study entry, had low-density lipoprotein (LDL)
      cholesterol levels of 100 to 190 mg per deciliter (2.6 to 4.9 mmol per liter),
      and had no known coronary heart disease to double-blind treatment with 80 mg of
      atorvastatin per day or placebo. The primary end point was a first nonfatal or
      fatal stroke. RESULTS: The mean LDL cholesterol level during the trial was 73 mg
      per deciliter (1.9 mmol per liter) among patients receiving atorvastatin and 129
      mg per deciliter (3.3 mmol per liter) among patients receiving placebo. During a
      median follow-up of 4.9 years, 265 patients (11.2 percent) receiving atorvastatin
      and 311 patients (13.1 percent) receiving placebo had a fatal or nonfatal stroke
      (5-year absolute reduction in risk, 2.2 percent; adjusted hazard ratio, 0.84; 95
      percent confidence interval, 0.71 to 0.99; P=0.03; unadjusted P=0.05). The
      atorvastatin group had 218 ischemic strokes and 55 hemorrhagic strokes, whereas
      the placebo group had 274 ischemic strokes and 33 hemorrhagic strokes. The five
      year absolute reduction in the risk of major cardiovascular events was 3.5
      percent (hazard ratio, 0.80; 95 percent confidence interval, 0.69 to 0.92;
      P=0.002). The overall mortality rate was similar, with 216 deaths in the
      atorvastatin group and 211 deaths in the placebo group (P=0.98), as were the
      rates of serious adverse events. Elevated liver enzyme values were more common in
      patients taking atorvastatin. CONCLUSIONS: In patients with recent stroke or TIA
      and without known coronary heart disease, 80 mg of atorvastatin per day reduced
      the overall incidence of strokes and of cardiovascular events, despite a small
      increase in the incidence of hemorrhagic stroke. (ClinicalTrials.gov number,
      NCT00147602 [ClinicalTrials.gov].).

PMID- 16899776
TI  - Concordance among gene-expression-based predictors for breast cancer.
AB  - BACKGROUND: Gene-expression-profiling studies of primary breast tumors performed
      by different laboratories have resulted in the identification of a number of
      distinct prognostic profiles, or gene sets, with little overlap in terms of gene
      identity. METHODS: To compare the predictions derived from these gene sets for
      individual samples, we obtained a single data set of 295 samples and applied five
      gene-expression-based models: intrinsic subtypes, 70-gene profile, wound
      response, recurrence score, and the two-gene ratio (for patients who had been
      treated with tamoxifen). RESULTS: We found that most models had high rates of
      concordance in their outcome predictions for the individual samples. In
      particular, almost all tumors identified as having an intrinsic subtype of basal
      like, HER2-positive and estrogen-receptor-negative, or luminal B (associated with
      a poor prognosis) were also classified as having a poor 70-gene profile,
      activated wound response, and high recurrence score. The 70-gene and recurrence
      score models, which are beginning to be used in the clinical setting, showed 77
      to 81 percent agreement in outcome classification. CONCLUSIONS: Even though
      different gene sets were used for prognostication in patients with breast cancer,
      four of the five tested showed significant agreement in the outcome predictions
      for individual patients and are probably tracking a common set of biologic
      phenotypes.

PMID- 16899777
TI  - A genomic strategy to refine prognosis in early-stage non-small-cell lung cancer.
AB  - BACKGROUND: Clinical trials have indicated a benefit of adjuvant chemotherapy for
      patients with stage IB, II, or IIIA--but not stage IA--non-small-cell lung cancer
      (NSCLC). This classification scheme is probably an imprecise predictor of the
      prognosis of an individual patient. Indeed, approximately 25 percent of patients
      with stage IA disease have a recurrence after surgery, suggesting the need to
      identify patients in this subgroup for more effective therapy. METHODS: We
      identified gene-expression profiles that predicted the risk of recurrence in a
      cohort of 89 patients with early-stage NSCLC (the lung metagene model). We
      evaluated the predictor in two independent groups of 25 patients from the
      American College of Surgeons Oncology Group (ACOSOG) Z0030 study and 84 patients
      from the Cancer and Leukemia Group B (CALGB) 9761 study. RESULTS: The lung
      metagene model predicted recurrence for individual patients significantly better
      than did clinical prognostic factors and was consistent across all early stages
      of NSCLC. Applied to the cohorts from the ACOSOG Z0030 trial and the CALGB 9761
      trial, the lung metagene model had an overall predictive accuracy of 72 percent
      and 79 percent, respectively. The predictor also identified a subgroup of
      patients with stage IA disease who were at high risk for recurrence and who might
      be best treated by adjuvant chemotherapy. CONCLUSIONS: The lung metagene model
      provides a potential mechanism to refine the estimation of a patient's risk of
      disease recurrence and, in principle, to alter decisions regarding the use of
      adjuvant chemotherapy in early-stage NSCLC.

PMID- 16899779
TI  - Clinical practice. Paget's disease of bone.

PMID- 16899780
TI  - Images in clinical medicine. Inguinal hernia.

PMID- 16899778
TI  - Neonatal-onset multisystem inflammatory disease responsive to interleukin-1beta
      inhibition.
AB  - BACKGROUND: Neonatal-onset multisystem inflammatory disease is characterized by
      fever, urticarial rash, aseptic meningitis, deforming arthropathy, hearing loss,
      and mental retardation. Many patients have mutations in the cold-induced
      autoinflammatory syndrome 1 (CIAS1) gene, encoding cryopyrin, a protein that
      regulates inflammation. METHODS: We selected 18 patients with neonatal-onset
      multisystem inflammatory disease (12 with identifiable CIAS1 mutations) to
      receive anakinra, an interleukin-1-receptor antagonist (1 to 2 mg per kilogram of
      body weight per day subcutaneously). In 11 patients, anakinra was withdrawn at
      three months until a flare occurred. The primary end points included changes in
      scores in a daily diary of symptoms, serum levels of amyloid A and C-reactive
      protein, and the erythrocyte sedimentation rate from baseline to month 3 and from
      month 3 until a disease flare. RESULTS: All 18 patients had a rapid response to
      anakinra, with disappearance of rash. Diary scores improved (P<0.001) and serum
      amyloid A (from a median of 174 mg to 8 mg per liter), C-reactive protein (from a
      median of 5.29 mg to 0.34 mg per deciliter), and the erythrocyte sedimentation
      rate decreased at month 3 (all P<0.001), and remained low at month 6. Magnetic
      resonance imaging showed improvement in cochlear and leptomeningeal lesions as
      compared with baseline. Withdrawal of anakinra uniformly resulted in relapse
      within days; retreatment led to rapid improvement. There were no drug-related
      serious adverse events. CONCLUSIONS: Daily injections of anakinra markedly
      improved clinical and laboratory manifestations in patients with neonatal-onset
      multisystem inflammatory disease, with or without CIAS1 mutations.
      (ClinicalTrials.gov number, NCT00069329 [ClinicalTrials.gov].).

PMID- 16899781
TI  - Case records of the Massachusetts General Hospital. Case 24-2006. A 40-year-old
      woman with hypotension after an overdose of amlodipine.

PMID- 16899782
TI  - Stroke--an equal opportunity for the initiation of statin therapy.

PMID- 16899783
TI  - Molecular signatures predict outcomes of breast cancer.

PMID- 16899784
TI  - A proposal for radical changes in the drug-approval process.

PMID- 16899785
TI  - Inhaled corticosteroids and children.

PMID- 16899786
TI  - Imatinib and altered bone and mineral metabolism.

PMID- 16899787
TI  - Thrombotic thrombocytopenic purpura.

PMID- 16899788
TI  - Severe anomaly of coronary-artery development.

PMID- 16899789
TI  - Arthrocentesis video.

PMID- 16899790
TI  - Trends in overweight from 1980 through 2001 among preschool-aged children
      enrolled in a health maintenance organization.
AB  - OBJECTIVE: To examine overweight trends over a 22-year period among preschool
      aged children from primarily middle-income families enrolled in a health
      maintenance organization. RESEARCH METHODS AND PROCEDURES: From well-child care
      visits to a Massachusetts health maintenance organization, we randomly selected
      one visit per child per calendar year, yielding a study sample of 120,680
      children seen at 366,109 visits from 1980 through 2001. Using multivariate
      logistic regression models accounting for repeated observations of individual
      children across years, we estimated trends in prevalence of overweight (weight
      for-length/height > or = 95th percentile) and at-risk-for-overweight (85th to
      95th percentile). RESULTS: Over the 22-year study period, the observed prevalence
      of overweight increased from 6.3% to 10.0% and at-risk-for-overweight increased
      from 11.1% to 14.4%. These increases were evident among all groups of children
      including infants < 6 months of age. Overall, the adjusted odds ratios were 1.21
      per decade (95% confidence interval, 1.17 to 1.25) for overweight and 1.06 per
      decade (95% confidence interval, 1.03 to 1.08) for at-risk-for-overweight.
      DISCUSSION: Rates of overweight are increasing in very young children, even
      infants, from primarily middle-class families.

PMID- 16899791
TI  - Prevalence of obesity in elementary schoolchildren living in Northeast Attica,
      Greece.
AB  - OBJECTIVE: To assess the prevalence of obesity and obesity trend in
      schoolchildren living in Northeast Attica, Greece. RESEARCH METHODS AND
      PROCEDURES: Mean (standard deviation) and median weight and BMI were calculated
      in 4131 (2054 boys and 2077 girls) 6- to 11-year-old Greek schoolchildren living
      in Northeast Attica between November 2003 and April 2004. Two hundred thirty-six
      (95 boys, 141 girls) immigrant children also participated in the study. The
      secular trend for obesity was determined comparing our data with those of a
      similar study performed in 1994. RESULTS: Of boys, 27.8% were overweight, and
      12.3% were obese. For girls, the corresponding values were 26.5% for overweight
      and 9.9% for obesity. There was an increase in the prevalence of overweight and
      obesity in the last 10 years in both sexes. For boys, overweight increased by
      4.2% and obesity by 2.9%, whereas, for girls, overweight increased by 3.8% and
      obesity by 1.6%. Overweight and obesity were less prevalent in the immigrant
      children compared with their Greek peers. For immigrant boys, overweight was
      15.9% and obesity was 7.9%, and for immigrant girls, overweight was 15.2% and
      obesity was 8.7%. DISCUSSION: Greek schoolchildren living in Northeast Attica
      present a high prevalence of overweight and obesity and a positive secular change
      in the prevalence of obesity.

PMID- 16899792
TI  - Weight gain induced by high-fat feeding involves increased liver oxidative
      stress.
AB  - OBJECTIVE: To assess the effects of high-fat feeding on white adipose tissue gene
      expression and liver oxidative stress. RESEARCH METHODS AND PROCEDURES: Male
      Wistar rats were fed on standard pelleted or high-fat diet to produce a diet
      induced obesity model. Therefore, body composition, serum biochemical values and
      liver malondialdehyde (MDA) were determined after 56 days of feeding. Expression
      (mRNA) values of three genes were also determined by reverse transcriptase
      polymerase chain reaction in white adipose tissue. RESULTS: Animals fed on the
      high-fat diet showed more body weight, higher fat deposition and total liver
      weight, and increased energy intake compared with those on the standard-fat diet.
      Serum fasting measurements (glucose, insulin, leptin) and homeostasis model
      assessment insulin resistance index were significantly increased by the high-fat
      diet consumption. As an indicator of oxidative stress, peroxide decomposition in
      liver was analyzed, showing an increase of MDA concentrations in rats fed on high
      fat diet in comparison with control rats. Interestingly, liver MDA levels
      correlated positively with body weight gain, serum leptin, and homeostasis model
      assessment. Finally, leptin and glycerol-3-phosphate dehydrogenase mRNA levels,
      but not fatty acid synthase, were increased by high-fat diet in comparison with
      the control-fed group. DISCUSSION: These results show a link among increased fat
      depots, insulin resistance, and liver oxidative stress. Thus, liver oxidative
      stress probably contributes to hepatic disorders and aggravates the metabolic
      syndrome, which is accompanied by a stimulation of the esterification of fatty
      acids as measured by glycerol-3-phosphate dehydrogenase in the adipose tissue,
      providing support to the hypothesis that not only calories count in the induction
      of weight gain or metabolic syndrome and that other factors such as oxidative
      stress may be involved.

PMID- 16899793
TI  - Glucose-dependent insulinotropic polypeptide modulates adipocyte lipolysis and
      reesterification.
AB  - OBJECTIVE: Glucose-dependent insulinotropic polypeptide (GIP) is an incretin
      released from intestinal K-cells during the postprandial period. Previous studies
      have suggested that GIP may play an etiologic role in obesity; thus, the GIP
      receptor may represent a target for anti-obesity drugs. The present studies were
      conducted to elucidate mechanisms by which GIP might promote obesity by examining
      the effect of GIP on both glycerol release (indicative of lipolysis) and free
      fatty acid (FFA) release (indicative of both lipolysis and reesterification), as
      well as the ability of a GIP-specific receptor antagonist (ANTGIP) to attenuate
      these effects. RESEARCH METHODS AND PROCEDURES: Isolated rat adipocytes were
      perifused on a column with 10 nM GIP alone or in combination with 10 microU/mL
      insulin, 1 microM isoproterenol, or 1 microM ANTGIP. Samples were collected every
      minute and assayed for FFA, glycerol, and lactate. RESULTS: GIP significantly
      increased FFA reesterification (decreased FFA release by 25%), stimulated
      lipolysis (increased glycerol release by 22%), and attenuated the lipolytic
      response to isoproterenol by 43%. These properties were similar to those of
      insulin in vitro, suggesting that GIP possesses insulin-like lipogenic effects on
      adipocytes. Finally, ANTGIP reversed the effects of GIP on both basal and
      stimulated adipocyte metabolism. DISCUSSION: These studies provide further
      evidence for an important physiological role for GIP in lipid homeostasis and
      possibly in the pathogenesis of obesity. They also suggest that the GIP receptor
      may represent an excellent target for the prevention and treatment of obesity and
      obesity-related type 2 diabetes.

PMID- 16899794
TI  - Cold exposure suppresses serum adiponectin levels through sympathetic nerve
      activation in mice.
AB  - OBJECTIVE: Several lines of evidence suggest important roles for adiponectin in
      glucose and lipid metabolism and atherosclerosis. However, the mechanisms
      regulating serum adiponectin levels and adiponectin production are still not
      completely understood. Our aim was to determine whether adiponectin synthesis is
      physiologically regulated by the sympathetic nervous system (SNS). RESEARCH
      METHODS AND PROCEDURES: Mice were exposed to cold (4 degrees C) for 12 hours and
      for 24 hours with or without inhibition of noradrenaline synthesis or pan-beta
      adrenergic function, followed by measurement of serum adiponectin concentrations
      and levels of adiponectin and uncoupling protein (UCP) 1 expressions in various
      white adipose tissues (WATs). RESULTS: Cold exposure significantly reduced serum
      adiponectin concentrations without changing body weights or WAT sizes in either
      subcutaneous or intra-abdominal fat tissues. The serum adiponectin reduction was
      associated with a decrease in adiponectin mRNA expression in subcutaneous,
      epididymal, and mesenteric fat tissues. In these adipose tissues, UCP1 expression
      was markedly enhanced, suggesting SNS activation in these tissues. Administration
      of alpha-methyl-p-tyrosine or a combination of SR59230A and propranolol reversed
      the cold-exposure-induced decreases in serum adiponectin concentrations and
      adiponectin mRNA expression in these tissues. In contrast, in retroperitoneal
      fat, the effects of cold exposure on adiponectin and UCP1 expressions were
      strikingly weak but were not reversed by SNS inhibitors. DISCUSSION: SNS
      physiologically regulates serum adiponectin levels and adiponectin synthesis in
      WATs in vivo, although responsiveness to SNS stimulation differs markedly among
      WATs. Sympathetic activation might be involved in development of the metabolic
      syndrome by modulation of serum adiponectin concentrations.

PMID- 16899795
TI  - Early obesity and age-related mimicry of metabolic syndrome in female mice with
      sex hormonal imbalances.
AB  - OBJECTIVE: To investigate the relationship of early obesity to metabolic syndrome
      during sex hormonal imbalances in mutant female mice at different ages. RESEARCH
      METHODS AND PROCEDURES: Hormonal imbalances, accumulation and nature of adipose
      tissue, food intake, glucose tolerance, and expression of candidate genes and
      markers of inflammation were studied by comparing wild-type, null, and
      haploinsufficient follitropin receptor knockout female mice at different ages.
      RESULTS: Follitropin receptor deletion in mice produced null females that are
      infertile and haploinsufficient mice that undergo accelerated biological aging.
      Both types of mutants with sex hormonal imbalances have central obesity without
      hyperphagia, but circulating leptin is elevated. Adipocyte hyperplasia and
      hypertrophy is attributed to elevated peroxisome proliferator-activated receptor
      gamma expression. Adiponectin protein levels increase in fat tissue and plasma.
      Only mutants but not controls acquire age-dependent decline in glucose tolerance
      with high insulin and altered pancreatic beta cells. Changes in inflammation
      markers, decreased muscle insulin receptor phosphorylation, and increase of the
      enzyme protein tyrosine phosphatase 1B indicate insulin resistance. DISCUSSION:
      In this animal model, the chronological appearance of early obesity induced by
      hormonal imbalances culminates in characteristics that are attributable to
      metabolic syndrome, including cardiovascular abnormalities. Dissection of the
      depot-specific alterations and defining molecular interrelationships could help
      in developing targeted remedies and resolving complications and controversies
      related to health benefits and adversities of current hormone replacement
      therapy.

PMID- 16899796
TI  - Visceral obesity is associated with high levels of serum squalene.
AB  - OBJECTIVE: To investigate the impact of visceral obesity on cholesterol
      metabolism in normoglycemic offspring of patients with type 2 diabetes. RESEARCH
      METHODS AND PROCEDURES: The proportion of intra-abdominal fat (IAF) was measured
      by abdominal computer tomography, and serum cholesterol synthesis and absorption
      markers were determined by gas-liquid chromatography in 109 normoglycemic
      offspring of patients with type 2 diabetes. Insulin action was measured with the
      hyperinsulinemic euglycemic clamp. The gene encoding squalene synthase (farnesyl
      diphosphate farnesyltransferase 1) was screened with the single-strand
      conformation polymorphism analysis and direct sequencing. RESULTS: Cholesterol
      synthesis markers correlated positively with IAF (r = 0.213 to 0.309, p < or =
      0.027) and negatively with the rates of insulin-stimulated whole-body glucose
      uptake (r = -0.372 to -0.248, p < or = 0.010). However, serum squalene, the first
      measured precursor of cholesterol synthesis, showed a positive correlation with
      IAF (r = 0.309, p = 0.001) without any association with subcutaneous fat or
      insulin sensitivity. Variation in the farnesyl-diphosphate farnesyltransferase 1
      gene did not explain elevated serum squalene levels in viscerally obese subjects.
      From the cholesterol absorption markers, cholestanol was associated negatively
      with IAF and positively with whole-body glucose uptake (p < 0.05). DISCUSSION:
      High serum squalene levels are associated with visceral obesity but not with
      subcutaneous obesity. Whether this finding is causally connected to visceral
      obesity remains to be established.

PMID- 16899797
TI  - Comparison of body fat composition and serum adiponectin levels in diabetic
      obesity and non-diabetic obesity.
AB  - OBJECTIVE: Clinical aspects of diabetes and obesity are somewhat different, even
      at similar levels of insulin resistance. The purpose of this study was to
      determine differences in body fat distribution and serum adiponectin
      concentrations in diabetic and non-diabetic obese participants. We were also
      interested in identifying the characteristics of insulin resistance in these two
      groups, particularly from the standpoint of adiponectin. RESEARCH METHODS AND
      PROCEDURES: Adiponectin concentrations of 112 type 2 diabetic obese participants
      and 124 non-diabetic obese participants were determined. Abdominal adipose tissue
      areas and midthigh skeletal muscle areas were measured by computed tomography. A
      homeostasis model assessment of the insulin resistance score was calculated to
      assess insulin sensitivity. The relationships among serum adiponectin, body fat
      distribution, and clinical characteristics were also analyzed. RESULTS: Both
      abdominal subcutaneous and visceral fat areas were higher in the non-diabetic
      obese group, whereas midthigh low-density muscle area was higher in the diabetic
      obese group. The homeostasis model assessment of the insulin resistance score was
      similar between groups, whereas serum adiponectin was lower in the diabetic obese
      group. Abdominal visceral fat (beta = -0.381, p = 0.012) was a more important
      predictor of adiponectin concentration than low-density muscle (beta = -0.218, p
      = 0.026) in cases of non-diabetic obesity, whereas low-density muscle (beta = 
      0.413, p = 0.013) was a better predictor of adiponectin level than abdominal
      visceral fat (beta = - 0.228, p = 0.044) in diabetic obese patients. DISCUSSION:
      Therefore, factors involved in pathophysiology, including different serum
      adiponectin levels and body fat distributions, are believed to be responsible for
      differences in clinical characteristics, even at similar levels of insulin
      resistance in both diseases.

PMID- 16899798
TI  - Effect of circulatory congestion on the components of pulmonary diffusing
      capacity in morbid obesity.
AB  - OBJECTIVE: Obese patients without clinically apparent heart disease may have a
      high output state and elevated total and central blood volumes. Central
      circulatory congestion should result in elevated pulmonary diffusing capacity
      (DLCO) and capillary blood volume (Vc) reflecting pulmonary capillary
      recruitment; however, the effect on membrane diffusion (Dm) is uncertain. We
      examined DLCO and its partition into Vc and Dm in 13 severely obese subjects (BMI
      = 51 +/- 14 kg/m2) without manifest cardiopulmonary disease before and after
      surgically induced weight loss. RESEARCH METHODS AND PROCEDURES: DLCO and its
      partition into Vc and Dm [referenced to alveolar volume (VA)] as described by
      Roughton and Forster, total body water by tritiated water, and fat distribution
      by waist-to-hip ratio were performed. RESULTS: Despite normal DLCO (mean 98 +/-
      16% predicted), Vc/VA was increased (mean 118 +/- 30% predicted), and Dm/VA was
      reduced (mean 77 +/- 34% predicted). Nine of 13 subjects were restudied after
      weight loss (mean 52 +/- 43 kg); Vc/VA decreased to 89 +/- 18% predicted (p =
      0.01), and Dm/VA increased to 139 +/- 30% predicted (p < 0.01). Increasing total
      body water was associated with both increasing Vc (r = 0.74, p = 0.01) and
      increasing waist-to-hip ratio (r = 0.65, p = 0.02), indicating that circulatory
      congestion increases with increasing central obesity. DISCUSSION: Severely obese
      subjects without manifest cardiopulmonary disease may have increased Vc
      indicating central circulatory congestion and reduced Dm suggesting associated
      alveolar capillary leak, despite normal DLCO. Reversibility with weight loss is
      in accord with reversibility of the hemodynamic abnormalities of obesity.

PMID- 16899799
TI  - Two-dimensional predictive equation to classify visceral obesity in clinical
      practice.
AB  - OBJECTIVE: Visceral obesity assessment is not easy, and although computed
      tomography (CT) is an accurate tool, this technique is expensive and sometimes
      not suitable in clinical practice. We developed a new two-dimensional elliptical
      anthropometric equation to classify visceral obesity and evaluated the validity
      and the reliability of the new equation compared with CT. RESEARCH METHODS AND
      PROCEDURES: We collected anthropometric and CT data from overweight/obese
      subjects (n = 61, BMI = 32.4 +/- 3.7 kg/m2). A validation group of 32 subjects
      was also selected. An equation for the assessment of visceral obesity was
      developed using multiple regression analysis. Once validated, the equation was
      compared with previous models. Tests for accuracy included mean differences,
      analysis of diagnostic, R2, Snedecor's F-test, and Bland-Altman plot. RESULTS:
      Multiple regression analysis revealed that the sagittal and coronal diameters and
      the triceps skinfold were significant contributors to the model. The final
      equation was: visceral area (VA)/subcutaneous area (SA)predicted = 0.868 + 0.064
      x sagittal diameter - 0.036 x coronal diameter - 0.022 x triceps skinfold.
      Patients with visceral-subcutaneous area ratio (VA/SA) > 0.42 were classified as
      having visceral obesity. The predictive equation was valid, showing a significant
      association with VA/SA assessed by CT (VA/SA(CT); r = 0.68; p < 0.0001). Paired
      Student's t test showed no significant differences with VA/SACT (p = 0.541). The
      reliability was high [F(24/60) = 2.12; p = 0.01]. DISCUSSION: The new two
      dimensional and elliptical predictive equation is valid to assess visceral
      obesity and is more precise than previous models.

PMID- 16899800
TI  - Genetic effects on obesity assessed by bivariate genome scan: the Mexican
      American coronary artery disease study.
AB  - OBJECTIVE: To identify the genetic determinants of obesity using univariate and
      bivariate models in a genome scan. RESEARCH METHODS AND PROCEDURES: We evaluated
      the genetic and environmental effects and performed a genome-wide linkage
      analysis of obesity-related traits in 478 subjects from 105 Mexican-American
      nuclear families ascertained through a proband with documented coronary artery
      disease. The available obesity traits include BMI, body surface area (BSA), waist
      to-hip ratio (WHR), and trunk fat mass as percentage of body weight. Heritability
      estimates and multipoint linkage analysis were performed using a variance
      components procedure implemented in SOLAR software. RESULTS: The heritability
      estimates were 0.62 for BMI, 0.73 for BSA, 0.40 for WHR, and 0.38 for trunk fat
      mass as percentage of body weight. Using a bivariate genetic model, we observed
      significant genetic correlations between BMI and other obesity-related traits
      (all p < 0.01). Evidence for univariate linkage was observed at 252 to
      approximately 267 cM on chromosome 2 for three obesity-related traits (except for
      WHR) and at 163 to approximately 167 cM on chromosome 5 for BMI and BSA, with the
      maximum logarithm of the odds ratio score of 3.12 (empirical p value, 0.002) for
      BSA on chromosome 2. Use of the bivariate linkage model yielded an additional
      peak (logarithm of the odds ratio = 3.25, empirical p value, 0.002) at 25 cM on
      chromosome 7 for the pair of BMI and BSA. DISCUSSION: The evidence for linkage on
      chromosomes 2q36-37 and 5q36 is supported both by univariate and bivariate
      analysis, and an additional linkage peak at 7p15 was identified by the bivariate
      model. This suggests that use of the bivariate model provides additional
      information to identify linkage of genes responsible for obesity-related traits.

PMID- 16899801
TI  - Skeletal muscle fat oxidation is increased in African-American and white women
      after 10 days of endurance exercise training.
AB  - OBJECTIVE: Obesity is associated with lower rates of skeletal muscle fatty acid
      oxidation (FAO), which is linked to insulin resistance. FAO is reduced further in
      obese African-American (AAW) vs. white women (CW) and may also be lower in lean
      AAW vs. CW. In lean CW, endurance exercise training (EET) elevates the oxidative
      capacity of skeletal muscle. Therefore, we determined whether EET would elevate
      skeletal muscle FAO similarly in AAW and CW with a lower lipid oxidative
      capacity. RESEARCH METHODS AND PROCEDURES: In vitro rates of FAO were assessed in
      rectus abdominus muscle strips using [1- 14C] palmitate (Pal) from lean AAW [BMI
      = 24.2 +/- 0.9 (standard error) kg/m2] and CW (23.6 +/- 0.8 kg/m2) undergoing
      voluntary abdominal surgery. Lean AAW (22 +/- 0.9 kg/m(2)) and CW (24 +/- 0.8
      kg/m2) and obese AAW (36 +/- 1.2 kg/m2) and CW (40 +/- 1.3 kg/m2) underwent 10
      consecutive days of EET on a cycle ergometer (60 min/d, 75% peak oxygen uptake).
      FAO was measured in vastus lateralis homogenates as captured 14CO2 using [1- 14C]
      Pal, palmitoyl-CoA (Pal-CoA), and palmityl-carnitine (Pal-Car). RESULTS: Muscle
      strip experiments showed suppressed rates of FAO (p = 0.03) in lean AAW vs. CW.
      EET increased the rates of skeletal muscle Pal oxidation (p = 0.05) in both lean
      AAW and CW. In obese subjects, Pre-EET Pal (but not Pal-CoA or Pal-Car) oxidation
      was lower (p = 0.05) in AAW vs. CW. EET increased Pal oxidation 100% in obese AAW
      (p < 0.05) and 59% (p < 0.05) in obese CW. Similar increases (p < 0.05) in post
      EET FAO were observed for Pal-CoA and Pal-Car in both groups. DISCUSSION: Both
      lean and obese AAW possess a lower capacity for skeletal muscle FAO, but EET
      increases FAO similarly in both AAW and CW. These data suggest the use of EET for
      treatment against obesity and diabetes for both AAW and CW.

PMID- 16899802
TI  - Energy restriction with different protein quantities and source: implications for
      innate immunity.
AB  - OBJECTIVE: Physical age, energy restriction (ER), and weight loss have been
      reported to suppress indices of innate immunity, which may increase the risk of
      illness. To evaluate these interactions, we recruited older, postmenopausal women
      (50 to 80 years) to fill one of the following 9-week ER (1250 kcal/d) groups:
      beef [n = 14; reported intakes 46% carbohydrate (CHO):24% protein (PRO):30% fat],
      chicken (n = 15; 51% CHO:25% PRO:24% fat), or CHO (n = 14; 59% CHO:17% PRO:24%
      fat), or a non-intervention control (n = 11). RESEARCH METHODS AND PROCEDURES:
      Fasting blood was collected before and after ER to determine leukocyte phenotype,
      neutrophil oxidative burst capacity, natural killer cell activity, stimulated
      interleukin-2 and interferon-gamma production, and blood zinc and iron
      concentrations. RESULTS: No significant effects of ER (8.6% weight loss) or PRO
      quantity and source were found for the majority of indices of innate immunity.
      Small but significant (p < 0.05) declines in interleukin-2 production were found
      in the chicken and CHO groups only; however, the clinical significance of this
      finding is not known. DISCUSSION: In the present study, 9 weeks of moderate ER
      did not suppress immunity in postmenopausal women. Also, contrary to our
      hypothesis, differential zinc and iron intakes did not significantly alter
      immunity.

PMID- 16899803
TI  - Intensive weight loss program improves physical function in older obese adults
      with knee osteoarthritis.
AB  - OBJECTIVE: Physical function and body composition in older obese adults with knee
      osteoarthritis (OA) were examined after intensive weight loss. RESEARCH METHODS
      AND PROCEDURES: Older obese adults (n = 87; > or = 60 years; BMI > or = 30.0
      kg/m2) with symptomatic knee OA and difficulty with daily activities were
      recruited for a 6-month trial. Participants were randomized into either a weight
      stable (WS) or weight loss (WL) program. Participants in WL (10% weight loss
      goal) were prescribed a 1000 kcal/d energy deficit diet with exercise 3 d/wk. WS
      participants attended health information sessions. Body composition and physical
      function (Western Ontario and McMaster University Osteoarthritis Index, 6-minute
      walking distance, and stair climb time) were assessed at baseline and 6 months.
      Statistical analysis included univariate analysis of covariance on 6-month
      measurements using baseline values as covariates. Associations between physical
      function and body composition were performed. RESULTS: Body weight decreased 8.7
      +/- 0.8% in WL and 0.0 +/- 0.7% in WS. Body fat and fat-free mass were lower for
      WL than WS at 6 months (estimated means: fat = 38.1 +/- 0.4% vs. 40.9 +/- 0.4%,
      respectively; fat-free mass = 56.7 +/- 0.4 vs. 58.8 +/- 0.4 kg, respectively). WL
      had better function than WS, with lower Western Ontario and McMaster University
      Osteoarthritis Index scores, greater 6-minute walk distance, and faster stair
      climb time (p < 0.05). Changes in function were associated with weight loss in
      the entire cohort. DISCUSSION: An intensive weight loss intervention
      incorporating energy deficit diet and exercise training improves physical
      function in older obese adults with knee OA. Greater improvements in function
      were observed in those with the most weight loss.

PMID- 16899804
TI  - Two-year internet-based randomized controlled trial for weight loss in African
      American girls.
AB  - OBJECTIVE: A randomized controlled trial tested the efficacy of an internet-based
      lifestyle behavior modification program for African-American girls over a 2-year
      period of intervention. RESEARCH METHODS AND PROCEDURES: Fifty-seven overweight
      (mean BMI percentile, 98.3) African-American girls (mean age, 13.2 years) were
      randomly assigned to an interactive behavioral internet program or an internet
      health education program, the control condition. Overweight parents were also
      participants in the study. Forty adolescent-parent dyads (70%) completed the 2
      year trial. Outcome data including BMI, body weight, body composition, and weight
      loss behaviors were collected at baseline and at 6-month intervals. A computer
      server tracked use of the web sites. RESULTS: An intention-to-treat statistical
      approach was used, with the last observation carried forward. In comparison with
      the control condition, adolescents in the behavioral program lost more mean body
      fat (BF) (-1.12 +/- 0.47% vs. 0.43 +/- 0.47% BF, p < 0.05), and parents in the
      behavioral program lost significantly more mean body weight (-2.43 +/- 0.66 vs. 
      0.35 +/- 0.64 kg, p < 0.05) during the first 6 months. This weight loss was
      regained over the next 18 months. After 2 years, differences in fat for
      adolescents (-0.08 +/- 0.71% vs. 0.84 +/- 0.72% BF) and weight for parents (-1.1
      +/- 0.91 vs. -0.60 +/- 0.89 kg) did not differ between the behavioral and control
      programs. DISCUSSION: An internet-based weight management program for African
      American adolescent girls and their parents resulted in weight loss during the
      first 6 months but did not yield long-term loss due to reduced use of the web
      site over time.

PMID- 16899805
TI  - Binge eating and weight loss in a self-help behavior modification program.
AB  - OBJECTIVE: To examine the occurrence of binge eating and its impact on weight
      loss outcomes among obese participants in the Trevose Behavior Modification
      Program, a lay-administered, lay-directed self-help weight loss program offering
      continuing care. RESEARCH METHODS AND PROCEDURES: Participants completed
      questionnaires, and weight loss data were recorded prospectively. RESULTS:
      Although objective bulimic episodes were reported by 41% of the sample, objective
      bulimic episodes were not associated with worse weight loss outcomes. Mean weight
      loss after 12 months was 18.2 kg (18.8% of initial body weight) for the treatment
      completers and 10.3 kg (10.5% of initial body weight) for the full sample (using
      intent-to-treat analyses, with baseline scores carried forward). DISCUSSION:
      Substantial long-term weight loss, resulting from a continuing care treatment
      program, occurred in individuals both with and without frequent binge eating.

PMID- 16899806
TI  - Fasting-based estimates of insulin sensitivity in overweight and obesity: a
      critical appraisal.
AB  - OBJECTIVE: To identify simple methods to estimate the degree of insulin
      resistance. RESEARCH METHODS AND PROCEDURES: The performance of a wide range of
      fasting-based index estimates of insulin sensitivity was compared by receiver
      operating characteristic analysis (area under curves and their 95% confidence
      intervals) against the M value from euglycemic insulin clamp studies collected in
      the San Antonio (non-Hispanic whites and Hispanic residents of San Antonio, TX)
      and European Group for the Study of Insulin Resistance (non-diabetic white
      Europeans) databases (n = 638). RESULTS: Insulin resistance differed
      substantially between lean (BMI < 25 kg/m2), overweight or obese (BMI > or = 25
      kg/m2), and type 2 diabetic individuals. Estimates of insulin resistance were,
      therefore, assessed in each group separately. In the overweight and obese
      subgroup (n = 302), the receiver operating characteristic performance of fasting
      based indices varied from 0.72 (0.62 to 0.82), in the case of the insulin/glucose
      ratio, to 0.80 (0.72 to 0.88) in the case of Belfiore free fatty acids. One
      superior method could not be identified; the confidence intervals overlapped, and
      no statistically significant differences emerged. All indices performed better
      when using the whole study population, with fasting plasma insulin, homeostatic
      model assessment, insulin/glucose ratio, quantitative insulin sensitivity check
      index, glucose/insulin ratio, Belfiore glycemia, revised quantitative insulin
      sensitivity check index, McAuley index, and Belfiore free fatty acids showing
      area under curves of 0.83, 0.90, 0.66, 0.90, 0.66, 0.90, 0.85, 0.83, and 0.86,
      respectively, because of the inclusion of very insulin sensitive (lean) and very
      insulin resistant cases (diabetic subjects). DISCUSSION: In conclusion, a
      superior fasting-based index estimate to distinguish between the presence and
      absence of insulin resistance in overweight and obesity could not be identified
      despite the use of the large datasets.

PMID- 16899807
TI  - Secular change in size at birth from 1973 to 2003: national data from Denmark.
AB  - OBJECTIVE: To explore whether birth weight (BW) has been increasing in Denmark at
      the same level as in other countries and whether this increase is paralleled by
      an increase in birth length (BL) or whether body proportionality, expressed as
      ponderal index (PI), has changed. RESEARCH METHODS AND PROCEDURES: This study
      used data analysis of information from The Danish Medical Birth Registry
      including all single live births in Denmark from 1973 to 2003 (n = 1,863,456).
      BW, BL, gestational age, maternal age, and smoking status (only from 1991 on)
      were measured. RESULTS: Mean BW increased steadily during the period (160 grams;
      equivalent to approximately 5 g/yr) at a rate higher than that reported from
      other countries. BL showed only a minor increase (2.4 mm), leading to an increase
      in PI (0.8 kg/m3) during the period. Controlling for the effect of increasing
      maternal age and decreasing gestational age and maternal smoking prevalence (only
      data after 1991), there was still an increase in BW of approximately 4 g/yr.
      DISCUSSION: During the last 30 years, neonates have become bigger, with a larger
      relative increase in BW than BL, leading to an increase in PI. The increasing BW
      and PI, which may be caused by increased maternal weight, could further promote
      the obesity epidemic.

PMID- 16899808
TI  - Adult obesity and number of years lived with and without cardiovascular disease.
AB  - OBJECTIVE: To determine the differences in number of years lived free of
      cardiovascular disease (CVD) and number of years lived with CVD between men and
      women who were obese, pre-obese, or normal weight at 45 years of age. RESEARCH
      METHODS AND PROCEDURES: We constructed multistate life tables for CVD, myocardial
      infarction, and stroke, using data from 2551 enrollees (1130 men) in the
      Framingham Heart Study who were 45 years of age. RESULTS: Obesity and pre-obesity
      were associated with fewer number of years free of CVD, myocardial infarction,
      and stroke and an increase in the number of years lived with these diseases.
      Forty-five-year-old obese men with no CVD survived 6.0 years [95% confidence
      interval (CI), 4.1; 8.1] fewer than their normal weight counterparts, whereas,
      for women, the difference between obese and normal weight subjects was 8.4 years
      (95% CI: 6.2; 10.8). Obese men and women lived with CVD 2.7 (95% CI: 1.0; 4.4)
      and 1.4 years (95% CI: -0.3; 3.2) longer, respectively, than normal weight
      individuals. DISCUSSION: In addition to reducing life expectancy, obesity before
      middle age is associated with a reduction in the number of years lived free of
      CVD and an increase in the number of years lived with CVD. Such information is
      paramount for preventive and therapeutic decision-making by individuals and
      practitioners alike.

PMID- 16899809
TI  - Anthropometric measures, body composition, body fat distribution, and knee
      osteoarthritis in women.
AB  - OBJECTIVE: Increased BMI is a well-recognized risk factor for radiographic knee
      osteoarthritis (rKOA); however, the contributions of the components of body
      composition, body fat distribution, and height to this association are not clear.
      RESEARCH METHODS AND PROCEDURES: We examined 779 women > or = 45 years of age
      from the Johnston County Osteoarthritis Project. Body composition was assessed
      using DXA, and rKOA was defined as Kellgren-Lawrence grade > or = 2. Logistic
      regression models examined the association between rKOA and the fourth compared
      with the first quartiles of anthropometric, body composition, and fat
      distribution measures adjusting for age, ethnicity, and prior knee injury.
      RESULTS: The adjusted odds ratios and 95% confidence interval of BMI and weight
      were 5.27 (3.05, 9.13) and 5.28 (3.05, 9.16), respectively. In separate models,
      higher odds of rKOA were also found for fat mass [4.54 (2.68, 7.69)], percent fat
      mass [3.84 (2.26, 6.54)], lean mass [3.94 (2.22, 6.97)], and waist circumference
      [4.15 (2.45, 7.02)]. Waist-to-hip ratio was not associated with rKOA [1.45 (0.86,
      2.43)], and percent lean mass was associated with lower odds [0.20 (0.11, 0.35)].
      Taller women had higher odds of rKOA after adjustment for BMI [1.77 (1.05,
      3.00)]. DISCUSSION: This study confirms that BMI and weight are strongly
      associated with rKOA in women and suggests that precise measurements of body
      composition and measures of fat distribution may offer no advantage over the more
      simple measures of BMI or weight in assessment of risk of rKOA.

PMID- 16899810
TI  - Functional characterization of male germ cell-specific CREM isoforms.
AB  - Due to alternative promoter usage, splicing, and translational initiation,
      expression of the cAMP-responsive element modulator (CREM) gene results in the
      production of functionally different CREM proteins with either activating or
      repressing potential on target gene expression. Recently, we demonstrated 2 novel
      isoforms (CREM-2-F-G-H-Ib and CREM-2-G-H-Ib) in various germ cell types during
      normal and impaired human spermatogenesis. In contrast to known isoforms, these
      exhibit a transactivation domain but lack a kinase-inducible domain (KID) domain
      resulting in a disruption of the open reading frame. In the present study, we
      functionally analyzed these isoforms. Investigation of both in vitro and in vivo
      expressed proteins from human testis RNA suggests that a novel upstream open
      reading frame in exon 2 is translated from isoform CREM-2-F-G-H-Ib, giving rise
      to a full-length protein. Furthermore, in both isoforms, usage of downstream
      adeninethymine-guanines (ATGs) for translation initiation could be observed.
      Sequence-specific DNA binding of CREM isoforms was confirmed by electrophoretic
      mobility shift assays. Luciferase reporter gene assays in cells transfected with
      novel CREM cDNAs demonstrated that protein kinase A dependent stimulation was
      inhibited by coexpression of CREM-2-F-G-H-Ib but not of CREM-2-G-H-Ib.

PMID- 16899811
TI  - Pesticides and polychlorinated biphenyls as potential risk factors for erectile
      dysfunction.
AB  - While it is biologically plausible that environmental chemicals such as
      pesticides and polychlorinated biphenyls (PCBs) with suspected hormone disrupting
      properties may have an impact on risk of erectile dysfunction (ED), few
      epidemiologic studies have assessed this potential association. In a clinic-based
      case-control study in Kingston, Ontario, consenting subjects completed a
      questionnaire and donated 15 mL of blood for analysis of organochlorines and
      lipids by gas chromatography. Exposures were compared for 101 cases with ED and
      234 comparable control subjects. For most PCB congeners and organochlorine
      pesticides, geometric mean levels are similar for cases and controls.
      Multivariate logistic regression results do not show an increased or decreased
      risk of ED associated with levels of most detectable environmental substances
      after adjustment for age, total lipids, and confounders. Levels of 2 of the
      ubiquitous chlorinated pesticides, oxychlordane and trans-nonachlor, which are
      highly correlated, appear to associate with a reduced risk of ED, but the role of
      chance cannot be ruled out. To our knowledge, this study is the first to
      investigate the possible relationship between plasma levels of organochlorines
      and ED risk, and results do not provide evidence of an association.

PMID- 16899812
TI  - Successful pregnancy and delivery following intracytoplasmic injection of frozen
      thawed nonviable testicular sperm and oocyte activation with calcium ionophore.

PMID- 16899813
TI  - Increased aneuploidy rate in sperm with fragmented DNA as determined by the sperm
      chromatin dispersion (SCD) test and FISH analysis.
AB  - Previous studies suggest that sperm DNA fragmentation may be associated with
      aneuploidy. However, currently available tests have not made it possible to
      simultaneously perform DNA fragmentation and chromosomal analyses on the same
      sperm cell. The recently introduced sperm chromatin dispersion (SCD) test allows
      users to determine this relationship. Semen samples from 16 males, including 4
      fertile donors, 7 normozoospermic, 3 teratozoospermic, 1 asthenozoospermic, and 1
      oligoasthenoteratozoospermic, were processed for DNA fragmentation analysis by
      the SCD test using the Halosperm kit. Three-color fluorescence in situ
      hybridization (FISH) was performed on SCD-processed slides to determine
      aneuploidy for chromosomes X, Y, and 18. Spermatozoa with DNA fragmentation
      showed a 4.4 +/- 1.9-fold increase in diploidy rate and a 5.9 +/- 3.5-fold
      increase in disomy rate compared to spermatozoa without DNA fragmentation. The
      overall aneuploidy rate was 4.6 +/- 2.0-fold higher in sperm with fragmented DNA
      (Wilcoxon rank test: P < .001 in the 3 comparisons). A higher frequency of DNA
      fragmentation was found in sperm cells containing sex chromosome aneuploidies
      originated in both first and second meiotic divisions. The observed increase in
      aneuploidy rate in sperm with fragmented DNA may suggest that the occurrence of
      aneuploidy during sperm maturation may lead to sperm DNA fragmentation as part of
      a genomic screening mechanism developed to genetically inactivate sperm with a
      defective genomic makeup.

PMID- 16899814
TI  - Metastatic prostate cancer after orchiectomy, radiotherapy, and testosterone
      replacement in a patient with bilateral seminoma.

PMID- 16899816
TI  - Cell surface actin remodeling.

PMID- 16899817
TI  - Farnesylated lamins, progeroid syndromes and farnesyl transferase inhibitors.
AB  - Three mammalian nuclear lamin proteins, lamin B(1), lamin B(2) and the lamin A
      precursor, prelamin A, undergo canonical farnesylation and processing at CAAX
      motifs. In the case of prelamin A, there is an additional farnesylation-dependent
      endoproteolysis, which is defective in two congenital diseases: Hutchinson
      Gilford progeria (HGPS) and restrictive dermopathy (RD). These two diseases arise
      respectively from defects in the prelamin A substrate and the enzyme (ZmpSte24)
      that processes it. Recent work has shed light on the roles of the lamin proteins
      and the enzymes involved in their farnesylation-dependent maturation. Other
      experimental work, including mouse model studies, have examined the possibility
      that farnesyl transferase inhibitors can represent effective treatment for HGPS.
      However, there are concerns about their use for this purpose given the potential
      for alternative prenylation pathways.

PMID- 16899818
TI  - Brain-specific BNIP-2-homology protein Caytaxin relocalises glutaminase to
      neurite terminals and reduces glutamate levels.
AB  - Human Cayman ataxia and mouse or rat dystonia are linked to mutations in the
      genes ATCAY (Atcay) that encode BNIP-H or Caytaxin, a brain-specific member of
      the BNIP-2 family. To explore its possible role(s) in neuronal function, we used
      protein precipitation and matrix-assisted laser desorption/ionisation mass
      spectrometry and identified kidney-type glutaminase (KGA) as a novel partner of
      BNIP-H. KGA converts glutamine to glutamate, which could serve as an important
      source of neurotransmitter. Co-immunoprecipitation with specific BNIP-H antibody
      confirmed that endogenous BNIP-H and KGA form a physiological complex in the
      brain, whereas binding studies showed that they interact with each other
      directly. Immunohistochemistry and in situ hybridisation revealed high BNIP-H
      expression in hippocampus and cerebellum, broadly overlapping with the expression
      pattern previously reported for KGA. Significantly, BNIP-H expression was
      activated in differentiating neurons of the embryonic carcinoma cell line P19
      whereas its overexpression in rat pheochromocytoma PC12 cells relocalised KGA
      from the mitochondria to neurite terminals. It also reduced the steady-state
      levels of glutamate by inhibiting KGA enzyme activity. These results strongly
      suggest that through binding to KGA, BNIP-H could regulate glutamate synthesis at
      synapses during neurotransmission. Thus, loss of BNIP-H function could render
      glutamate excitotoxicity or/and deregulated glutamatergic activation, leading to
      ataxia, dystonia or other neurological disorders.

PMID- 16899819
TI  - RhoA-kinase coordinates F-actin organization and myosin II activity during
      semaphorin-3A-induced axon retraction.
AB  - Axon guidance is mediated by the effects of attractant and repellent guidance
      cues on the cytoskeleton of growth cones and axons. During development, axon
      retraction is an important aspect of the pruning of inappropriately targeted
      axons in response to repellent guidance cues. I investigated the roles of RhoA
      kinase and myosin II in semaphorin-3A-induced growth cone collapse and axon
      retraction. I report that semaphorin 3A activates myosin II in growth cones and
      axons. Myosin II activity is required for axon retraction but not growth cone
      collapse. Furthermore, semaphorin 3A promotes the formation of intra-axonal F
      actin bundles in concert with the loss of F-actin in growth cone lamellipodia and
      filopodia. Formation of axonal F-actin bundles was independent of myosin II, but
      partially required RhoA-kinase activity. Conversely, RhoA-kinase activity was
      required to shut down F-actin polymerization underlying protrusive activity.
      Collectively, these observations suggest that guidance cues cause axon retraction
      through the coordinated activation of myosin II and the formation of intra-axonal
      F-actin bundles for myosin-II-based force generation. I suggest that in the
      context of semaphorin 3A signaling, RhoA-kinase serves as a switch to change the
      function of the F-actin cytoskeleton from promoting protrusive activity to
      generating contractile forces.

PMID- 16899820
TI  - Competition and cooperation between tenascin-R, lecticans and contactin 1
      regulate neurite growth and morphology.
AB  - The extracellular matrix molecule tenascin-R (TN-R) and the proteoglycans of the
      lectican family show an overlapping distribution in the developing brain, have
      been implicated in similar cellular processes and form a complex network of
      interactions. Previously, we have demonstrated that TN-R induces microprocesses
      along neurites and enlarged growth cones of tectal cells by interacting with the
      cell adhesion molecule contactin 1. Here, we describe competition and cooperation
      between TN-R, lecticans and contactin 1, and their functional consequences for
      tectal cells. Aggrecan, brevican and neurocan inhibit the effects of TN-R on
      microprocess formation and growth cone size. This blocking effect is due to
      competition of lecticans with binding of TN-R to its neuronal receptor contactin
      1, as shown by a sandwich-binding assay. Interaction of aggrecan with TN-R
      fibronectin type III domains 4-A is necessary for its inhibitory effect on both
      microprocess formation and TN-R binding to contactin 1. However, the chondroitin
      sulfate chains are not involved. Time-lapse video microscopy showed that aggrecan
      has no acute effect on motility and morphology of microprocesses and growth cones
      but induces long-term neurite retraction after pre-treatment with TN-R. In
      contrast to the competition described above, TN-R cooperates with brevican and
      neurocan to induce attachment of tectal cells and neurite outgrowth, probably by
      forming a bridge between the lectican substrate and contactin 1 as the neuronal
      receptor. Our findings suggest that a complex network of protein-protein
      interactions within the brain extracellular matrix, as shown here for TN-R and
      lecticans, is important for the fine-regulation of developmental processes such
      as microprocess formation along the neurite and neurite outgrowth.

PMID- 16899822
TI  - Dihydroxydocosahexaenoic acids of the neuroprotectin D family: synthesis,
      structure, and inhibition of human 5-lipoxygenase.
AB  - During aerobic oxidation of docosahexaenoic acid (DHA), soybean lipoxygenase
      (sLOX) has been shown to form 7,17(S)-dihydro(pero)xydocosahexaenoic acid
      [7,17(S)-diH(P)DHA] along with its previously described positional isomer,
      10,17(S)-dihydro(pero)xydocosahexa-4Z,7Z,11E,13Z,15E,19Z-enoic acid. 7,17(S)
      diH(P)DHA was also obtained via sLOX-catalyzed oxidation of either 17(S)
      hydroperoxydocosahexaenoic acid [17(S)-HPDHA] or 17(S)-hydroxydocosahexaenoic
      acid [17(S)-HDHA]. The structures of the products were elucidated by normal
      phase, reverse-phase, and chiral-phase HPLC analyses and by ultraviolet, NMR, and
      tandem mass spectroscopy and GC-MS. 7,17(S)-diH(P)DHA was shown to have
      4Z,8E,10Z,13Z,15E,19Z geometry of the double bonds. In addition, a compound
      apparently identical to the sLOX-derived 7,17(S)-diH(P)DHA was produced by
      another enzyme, potato tuber LOX, in the reactions of oxygenation of either 17(S)
      HPDHA or 17(S)-HDHA. All of the dihydroxydocosahexaenoic acids (diHDHAs) formed
      by either of the enzymes were clearly produced through double lipoxygenation of
      the corresponding substrate. 7,17(S)-diHDHA inhibited human recombinant 5
      lipoxygenase in the reaction of arachidonic acid (AA) oxidation. In standard
      conditions with 100 microM AA as substrate, the IC(50) value for 7,17(S)-diHDHA
      was found to be 7 microM, whereas IC(50) for 10,17(S)-DiHDHA was 15 microM.
      Similar inhibition by the diHDHAs was observed with sLOX, a quintessential 15LOX,
      although the strongest inhibition was produced by 10,17(S)-diHDHA (IC(50) = 4
      microM). Inhibition of sLOX by 7,17(S)-diHDHA was slightly less potent, with an
      IC(50) value of 9 microM. These findings suggest that 7,17(S)-diHDHA along with
      its 10,17(S) counterpart might have anti-inflammatory and anticancer activities,
      which could be exerted, at least in part, through direct inhibition of 5LOX and
      15LOX.

PMID- 16899821
TI  - A computational model of intracellular oxygen sensing by hypoxia-inducible factor
      HIF1 alpha.
AB  - Hypoxia-inducible factor-1, HIF1, transcriptionally activates over 200 genes
      vital for cell homeostasis and angiogenesis. We developed a computational model
      to gain a detailed quantitative understanding of how HIF1 acts to sense oxygen
      and respond to hypoxia. The model consists of kinetic equations describing the
      intracellular variation of 17 compounds, including HIF1, iron, prolyl
      hydroxylase, oxygen, ascorbate, 2-oxoglutarate, von Hippel Lindau protein and
      associated complexes. We tested an existing hypothesis of a switch-like change in
      HIF1 expression in response to a gradual decrease in O2 concentration. Our model
      predicts that depending on the molecular environment, such as intracellular iron
      levels, the hypoxic response varies considerably. We show HIF1-activated cellular
      responses can be divided into two categories: a steep, switch-like response to O2
      and a gradual one. Discovery of this dual response prompted comparison of two
      therapeutic strategies, ascorbate and iron supplementation, and prolyl
      hydroxylase targeting, to predict under what microenvironments either effectively
      increases HIF1alpha hydroxylation. Results provide crucial insight into the
      effects of iron and prolyl hydroxylase on oxygen sensing. The model advances
      quantitative molecular level understanding of HIF1 pathways--an endeavor that
      will help elucidate the diverse responses to hypoxia found in cancer, ischemia
      and exercise.

PMID- 16899823
TI  - GOLD stage 0 COPD: is it real? Does it matter?

PMID- 16899824
TI  - Is systemic inflammation responsible for pulmonary hypertension in COPD?

PMID- 16899825
TI  - Autotitrating CPAP: how shall we judge safety and efficacy of a "black box"?

PMID- 16899826
TI  - Nurse-conducted smoking cessation in patients with COPD, using nicotine
      sublingual tablets and behavioral support.

PMID- 16899827
TI  - What story do the pictures of cough tell us?

PMID- 16899828
TI  - Can global initiative for Chronic Obstructive Lung Disease stage 0 provide
      prognostic information on long-term mortality in men?
AB  - STUDY OBJECTIVES: To determine if the Global Initiative for Chronic Obstructive
      Lung Disease (GOLD) stage 0 (subjects at risk for COPD) provides information
      about long-term mortality risk. DESIGN, SETTING, AND PARTICIPANTS: From 1972 to
      1975, clinical, physiologic, and biochemical parameters including respiratory
      symptoms, spirometry, and physical fitness were measured in 1,999 healthy men
      aged 40 to 59 years in an occupational cohort, of whom 1,623 had acceptable
      spirometry findings. In a proportional hazards model with follow-up until 2000,
      we assessed all-cause mortality according to GOLD stage 0, I, II, and III
      compared with "normal" subjects, after adjusting for known risk factors and
      potential confounders. RESULTS: After 26 years (range, 25 to 27 years), 615 men
      (38%) had died. In multivariate proportional hazards models, GOLD stage 0
      subjects had a nonsignificantly increased hazard of death (hazard ratio [HR],
      1.19; p = 0.21) after adjustment for age, smoking, physical fitness, body mass
      index, systolic BP, and serum cholesterol. Similarly, subjects in GOLD stage I
      (HR, 1.30; p = 0.05) and stage II (HR, 1.77; p < 0.0001) had increased all-cause
      mortality. When expanding GOLD stage 0 to comprise patients with any respiratory
      symptom in a sensitivity analysis, the HR for all-cause mortality increased (HR,
      1.35; p = 0.03). CONCLUSION: There probably is an excess mortality among GOLD
      stage 0 subjects compared to symptom-free subjects; however, this should be
      interpreted cautiously and the results vary with the definition of the GOLD stage
      0. Subjects in GOLD stage I or stage II had higher mortality than symptom-free
      subjects.

PMID- 16899829
TI  - Systemic inflammation in patients with COPD and pulmonary hypertension.
AB  - STUDY OBJECTIVES: COPD is a systemic disorder that is associated with increases
      of inflammatory proteins in systemic circulation. However, no data on the
      potential role of systemic inflammation in pulmonary hypertension secondary to
      COPD are available. Therefore, our aim was to investigate the degree of systemic
      inflammation reflected by circulatory levels of C-reactive protein (CRP), tumor
      necrosis factor (TNF)-alpha, and interleukin (IL)-6 in COPD patients with and
      without pulmonary hypertension. DESIGN: Cross-sectional study. SETTING:
      University hospital, tertiary referral setting. PATIENTS AND MEASUREMENTS: In 43
      consecutive patients with COPD (mean [+/- SD] age, 65.0 +/- 10.5 years; mean
      FEV(1), 46.2 +/- 18.1% predicted), lung function was assessed using body
      plethysmography; pulmonary artery pressure (Ppa) levels were measured by
      echocardiography. Serum TNF-alpha and IL-6 levels were assessed by enzyme-linked
      immunosorbent assay, and high-sensitivity serum CRP levels were measured by
      chemiluminescent immunoassay. RESULTS: Pulmonary hypertension was present in 19
      patients and was absent in 24 patients. In patients with pulmonary hypertension,
      serum CRP and TNF-alpha levels were significantly higher than in those patients
      without hypertension (median, 3.6 mg/L [25th to 75th percentile, 1.4 to 13.0
      mg/L] vs 1.8 mg/L [25th to 75th percentile, 0.8 to 2.8 mg/L; p = 0.034]; and
      median, 4.2 pg/mL [25th to 75th percentile, 3.4 to 10.9 pg/mL] vs 3.1 pg/mL [25th
      to 75th percentile, 2.1 to 4.2 pg/mL]; p = 0.042, respectively). No differences
      were seen in serum IL-6 (median, 10.4 pg/mL [25th to 75th percentile, 8.8 to 12.2
      pg/mL] vs 10.5 pg/mL [25th to 75th percentile, 9.4 to 39.1 pg/mL]; p = 0.651)
      between the groups. In multiple linear regression analysis, the following two
      variables were independent predictors of systolic Ppa (R(2) = 0.373): Pao(2) (p =
      0.011); and log-transformed serum CRP level (p = 0.044). CONCLUSION: We conclude
      that increases in Ppa in patients with COPD are associated with higher serum
      levels of CRP and TNF-alpha, raising the possibility of a pathogenetic role for
      low-grade systemic inflammation in the pathogenesis of pulmonary hypertension in
      COPD patients.

PMID- 16899830
TI  - Nurse-conducted smoking cessation in patients with COPD using nicotine sublingual
      tablets and behavioral support.
AB  - CONTEXT: Few studies have examined the effect of nicotine replacement therapy
      (NRT) in COPD patients. STUDY OBJECTIVE: To evaluate the efficacy of nicotine
      sublingual tablets and two levels of support for smoking cessation in COPD
      patients. DESIGN: Double-blind, multicenter, placebo-controlled smoking cessation
      trial. SETTING: Pulmonary outpatient clinics. PATIENTS: Three hundred seventy
      COPD patients who smoked a mean of 19.6 cigarettes per day (mean, 42.7 pack
      years; mean FEV(1), 56% of predicted). INTERVENTIONS: Nicotine sublingual tablet
      or placebo for 12 weeks combined with either low support (four visits plus six
      telephone calls) or high support (seven visits plus five telephone calls)
      provided by nurses. MEASUREMENTS: Carbon monoxide-verified abstinence rates and
      St. George Respiratory Questionnaire (SGRQ) assessed at 6 months and 12 months.
      RESULTS: Two hundred eighty-eight of 370 patients were evaluable for the final
      study end points. Smoking cessation rates were statistically significantly
      superior with sublingual nicotine vs placebo for all measures of abstinence: 6
      month point prevalence, 23% vs 10%; 12-month point prevalence, 17% vs 10%. There
      was no significant difference in effect between low vs high behavioral support.
      The SGRQ score improved significantly in abstainers vs nonabstainers; the changes
      in mean scores were -10.9 vs - 2.9 for total score, and - 28.6 vs - 2.3 for
      symptom score, respectively. CONCLUSIONS: This trial demonstrated the long-term
      efficacy of NRT for cessation for the general population of COPD smokers,
      regardless of daily cigarette consumption. Cessation success rates were in the
      same range as in healthy smokers, and abstinence improved SGRQ scores. NRT should
      be used to aid cessation in all smokers with COPD, regardless of disease severity
      and number of cigarettes smoked.

PMID- 16899831
TI  - Bench evaluation of flow limitation detection by automated continuous positive
      airway pressure devices.
AB  - STUDY OBJECTIVE: Automatic continuous positive airway pressure (CPAP) devices
      that adjust the pressure delivered to the patient are now available to treat
      sleep-disordered breathing. Sophisticated auto-CPAP devices can detect and
      correct flattened inspiratory flow contours (FIFCs) associated with subtle upper
      airway obstruction. However, evaluations of their performance are made difficult
      by differences across patients and devices. We performed a bench study of five
      commercially available auto-CPAP devices using a breath waveform simulator to
      evaluate sensitivity for detecting flattened inspiratory flow. DESIGN: Five
      degrees of FIFC were simulated. In addition, normal and abnormal flow contours
      from patients published in the literature were evaluated. MEASUREMENTS AND
      RESULTS: One device showed autotriggering leading to CPAP increases, and another
      device varied the CPAP level independently from the presence of an FIFC. The
      three remaining devices differed regarding the detection of FIFCs and the means
      used to increase CPAP. CONCLUSION: Based on the characteristics of each patient,
      physicians must choose among devices with different thresholds of FIFC detection
      and different pressure responses to detection. Therefore, physicians need details
      on the algorithms used in auto-CPAP devices. Manufacturers should supply detailed
      algorithms.

PMID- 16899832
TI  - Bench model to simulate upper airway obstruction for analyzing automatic
      continuous positive airway pressure devices.
AB  - BACKGROUND: Automatic positive airway pressure (APAP) devices are increasingly
      being used in patients with obstructive sleep apnea. Some APAP devices present an
      unstable behavior when subjected to some events or artifacts. The aims were to
      develop a bench model capable of reproducing real flow, snoring, and obstructive
      patterns and to compare the response of APAP devices based on flow and snoring
      with other devices using, in addition, the forced oscillation technique (FOT).
      METHODS: The bench model subjected APAP devices to apneas with and without
      obstruction, obstructive hypopneas with and without snoring, periods of flow
      limitation, and artifacts such as leaks and mouth expiration. RESULTS: Almost all
      the devices increased the pressure when subjected to apneas with obstruction, but
      at different rates. The time required by each device to reach 10 cm H(2)O ranged
      from 2.5 to 13 min. In the presence of apneas without obstruction, all the
      devices based on flow and snoring increased the pressure at the same rate as
      during apneas with obstruction. However, the devices using FOT did not modify the
      pressure. Four devices did not modify the pressure in the presence of obstructive
      hypopneas, and all but one device increased the pressure in the presence of
      snoring. Mask leaks had little effect on the response of the devices, but four
      devices increased the pressure during mouth expiration artifacts. CONCLUSIONS:
      When, in addition to the flow and snoring signals, the measurement of the upper
      airway resistance is included, the accuracy of the event detection algorithms is
      improved.

PMID- 16899833
TI  - Interpreting the histopathology of chronic cough: a prospective, controlled,
      comparative study.
AB  - HYPOTHESIS: Trauma from chronic coughing produces airway inflammation similar to
      diseases causing cough. DESIGN: Prospective, cross-sectional, controlled,
      clinicopathologic correlation study in four groups: group 1, cough from
      intrapulmonary diseases; group 2, cough from extrapulmonary diseases; group 3,
      cough that was unexplained; and group 4, nonsmoking, asymptomatic control
      subjects. METHODS: Patients with chronic cough underwent a standardized workup
      including endobronchial biopsies before treatment. Causes were determined by a
      favorable response to therapy. Bronchial biopsy samples from control subjects
      were obtained from surgical specimens. RESULTS: There were 24 adult subjects (13
      women and 11 men) with mean cough duration of 8.6 +/- 7.4 years (+/- SD).
      Thirteen patients had cough due to a specific disease: intrapulmonary diseases in
      5 patients, and extrapulmonary diseases in 8 patients. Eleven patients had
      unexplained cough. Compared to control subjects, there was minimal-to-moderate
      chronic inflammation in all coughers (p < or = 0.0004), in group 1 (p < or =
      0.039), group 2 (p = 0.061), and group 3 (p < or = 0.025) diseases that were not
      correlated with cough duration. There was no difference in type of inflammation,
      cough duration, or smoking history between groups, nor were there histologic
      differences between subjects with explained causes of cough compared with
      unexplained cough. CONCLUSIONS: Our findings suggest that airway inflammation
      associated with chronic cough, assessed on morphologic appearance and
      inflammatory cell counting in hematoxylin-eosin-prepared samples, may be due to
      the trauma of coughing, and the inflammation may be similar to that seen with
      diseases putatively thought to cause chronic cough. Investigators must be
      cautious when attributing pathogenic importance to observed inflammatory changes
      in airways of coughing subjects.

PMID- 16899834
TI  - Chemokine concentrations and mast cell chemotactic activity in BAL fluid in
      patients with eosinophilic bronchitis and asthma, and in normal control subjects.
AB  - BACKGROUND: Asthma and eosinophilic bronchitis share many immunopathologic
      features including increased numbers of eosinophils and mast cells in the
      superficial airway. The mast cell chemotactic activity of airway secretions has
      not been assessed in patients with eosinophilic bronchitis. OBJECTIVES: To
      investigate the concentration of chemokines in bronchial wash samples and BAL
      fluid, and the mast cell chemotactic activity in BAL fluid from subjects with
      asthma and eosinophilic bronchitis, and from healthy control subjects. METHODS:
      We measured the concentrations of CCL11, CXCL8, and CXCL10 in bronchial wash
      samples and BAL fluid from 14 subjects with eosinophilic bronchitis, 14 subjects
      with asthma, and 15 healthy control subjects. Mast cell chemotaxis to BAL fluid
      from these subjects was examined using the human mast cell line HMC-1. RESULTS:
      The bronchial wash sample and BAL fluid concentrations of CXCL10 and CXCL8 was
      increased in subjects with eosinophilic bronchitis compared to those in subjects
      with asthma and healthy control subjects (p < 0.05). The CCL11 concentration was
      below the limit of detection in most subjects. BAL fluid from subjects with
      eosinophilic bronchitis was chemotactic for mast cells (1.4-fold migration
      compared to a control, 95% confidence interval, 1.1 to 1.9; p = 0.04) and was
      inhibited by blocking CXCR1 (45% inhibition; p = 0.002), CXCR3 (38% inhibition; p
      = 0.034), or both (65% inhibition; p = 0.01). BAL fluid from the subjects with
      asthma and healthy control subjects was not chemotactic for mast cells. Mast cell
      migration to BAL fluid was correlated with the concentration of CXCL8 (r = 0.42;
      p = 0.031) and CXCL10 (r = 0.52; p = 0.007). CONCLUSION: In subjects with
      eosinophilic bronchitis, CXCL8 and CXCL10 concentrations were elevated in airway
      secretions. These chemokines may play a key role in mast cell recruitment to the
      superficial airway in this condition.

PMID- 16899835
TI  - Cough in COPD: correlation of objective monitoring with cough challenge and
      subjective assessments.
AB  - BACKGROUND: The relationships between objective cough rates, cough reflex
      sensitivity, subjective estimates of cough frequency, and cough-related quality
      of life in patients with COPD are poorly understood. SUBJECTS: Twenty-six
      patients with stable COPD who complained of cough (76.9% men; mean +/- SD age,
      68.7 +/- 6.9 years; mean FEV(1), 54.2 +/- 12.0% of predicted; median smoking
      history, 42.4 pack-years [range, 13 to 135 pack-years]). METHODS: Subjects
      performed a cough challenge test, ambulatory daytime and overnight sound
      recordings, scored the severity of cough (0 to 5 score and visual analog scale)
      for each recording period, and completed a cough-specific quality of life
      questionnaire (CQLQ). Coughs were counted manually and quantified in terms of
      cough seconds per hour (cs/h): the number of seconds within the recording that
      contain cough. RESULTS: Overall median time spent coughing was 7.5 cs/h (range,
      2.7 to 23.1 cs/h; daytime median, 12.4 cs/h [range, 3.3 to 40.4 cs/h]; overnight,
      1.9 cs/h [0.0 to 19.0 cs/h]) [p = <0.01]. Median log concentration of citric acid
      eliciting five coughs (C5) was - 0.9 mol/L (range, - 1.5 to 0.0 mol/L). Day time
      but not overnight time spent coughing was significantly correlated with log C5
      (log C5 r = - 0.49, p = 0.02, and r = - 0.20, p = 0.37, respectively). Subjective
      cough scores and visual analog scales were moderately associated with objective
      time spent coughing: daytime (r = 0.37, p = 0.03, and r = 0.41, p = 0.03) and
      overnight (r = 0.48, p = <0.01, and r = 0.5, p = 0.01), respectively.
      CONCLUSIONS: Subjective measures of cough and cough reflex sensitivity are
      statistically related to time spent coughing in patients with COPD, but with low
      to-moderate levels of correlation. These measures have insufficient predictive
      value to substitute for objective time spent coughing; however, in conjunction
      with the CQLQ, they may provide a qualitative dimension to the assessment of
      cough.

PMID- 16899836
TI  - Nonacid reflux in patients with chronic cough on acid-suppressive therapy.
AB  - BACKGROUND: It is generally accepted that extraesophageal gastroesophageal reflux
      disease (GERD) symptoms and their persistence despite acid-suppressive therapy
      are poor prognostic factors for antireflux surgery. Recent studies indicating
      that cough can be temporally associated with reflux episodes of pH 4 to 7 (ie,
      nonacid reflux) reinvigorates the need for a more careful workup in patients with
      cough suspected to be due to GERD. AIM: To evaluate the frequency of chronic
      cough associated with nonacid reflux and the response of these patients to
      laparoscopic Nissen fundoplication. METHODS: We retrospectively reviewed data
      from patients with persistent cough despite twice-daily proton pump inhibitor
      (PPI) with or without the use of nighttime regimens of histamine-2 receptor
      antagonist (H2RA), who had undergone combined multichannel intraluminal impedance
      and pH monitoring. The association of cough and reflux was evaluated by
      calculating the symptom index (SI) [positive if > or = 50%]. A subset of patients
      with positive SI values for impedance-detected reflux with therapy was referred
      for laparoscopic Nissen fundoplication. RESULTS: Of 50 patients (38 female
      patients; mean age, 43 years; age range, 6 months to 84 years) who were monitored
      while receiving therapy, 13 patients (26%) had a positive SI for cough. The SI
      positive group had a lower percentage of female patients and patients of younger
      age compared to the SI-negative group. Laparoscopic Nissen fundoplication was
      performed in six SI-positive patients who became asymptomatic and stopped
      receiving acid-suppressive therapy during follow-up evaluations (median time, 17
      months; range, 12 to 27 months). CONCLUSION: Impedance pH monitoring should be
      performed while receiving therapy in patients with persistent symptoms who are
      receiving PPI therapy. A positive SI for nonacid reflux may be helpful in
      selecting patients who will benefit from antireflux surgery.

PMID- 16899837
TI  - Oleic acid vs saline solution lung lavage-induced acute lung injury: effects on
      lung morphology, pressure-volume relationships, and response to positive end
      expiratory pressure.
AB  - OBJECTIVE: To compare two lung injury models (oleic acid [OA] and saline solution
      washout [SW]) regarding lung morphology, regional inflation, and recruitment
      during static pressure-volume (PV) curves, and the effects of positive end
      expiratory pressure (PEEP) below and above the lower inflection point (Pflex).
      METHODS: Fourteen adult pigs underwent OA or SW lung injury. Lung volumes were
      measured using CT. PV curves were obtained with simultaneous CT scanning at lung
      apex and base. Fractional inflation and recruitment were compared to data on PEEP
      above and below Pflex. RESULTS: Severity of lung injury was comparable. At zero
      PEEP, SW showed an increased amount of edema and poorly aerated lung volume,
      recruitment during inspiration, and a better oxygenation response with PEEP.
      Whole-lung PV curves were similar in both models, reflecting changes in alveolar
      inflation or deflation. On the inspiratory PV limb, recruitment and inflation
      were on the same line, while there was a substantial difference between deflation
      and derecruitment on the expiratory limb. PEEP-induced recruitment at lung apex
      and base was at or above the derecruitment line on the expiratory limb and showed
      no relationship to the whole-lung expiratory PV curve. CONCLUSIONS: The following
      conclusions were made: (1) OA and SW models are comparable in mechanics but not
      in lung injury characteristics; (2) neither inspiratory nor expiratory whole-lung
      PV curves are useful to select PEEP in order to optimize recruitment; and (3)
      after recruitment, there is no difference in derecruitment between the models at
      high PEEP, while more collapse occurs at lower PEEP in the basal sections of SW
      lungs.

PMID- 16899838
TI  - Peritoneal perfusion with oxygenated perfluorocarbon augments systemic
      oxygenation.
AB  - BACKGROUND: Despite maximal ventilatory support, many patients die from hypoxia
      in the setting of potentially reversible pulmonary failure. There remains a
      pressing need for additional pulmonary supportive care measures, especially
      techniques that do not require systemic anticoagulation. The objective of our
      experiments was to determine whether systemic oxygenation could be increased in a
      large animal, with induced hypoxia, by perfusing the abdominal cavity with
      oxygenated perfluorocarbons. METHODS: Fifteen pigs with a mean (+/- SD) weight of
      45 +/- 5 kg were intubated and rendered hypoxic by ventilating them with a blend
      of nitrogen and oxygen to achieve subatmospheric concentrations of inspired
      oxygen ranging from 18 to 10%, resulting in baseline mean Pao(2) range of 65.9 +/
      9.7 to 26.6 +/- 2.8 mm Hg, respectively. Peritoneal perfusion was performed in
      eight animals with oxygenated perfluorocarbon and in seven control animals with
      oxygenated saline solution. RESULTS: The average increase in Pao(2) with
      oxygenated perfluorocarbon perfusion, compared to oxygenated saline solution
      perfusion, ranged from 8.1 to 18.2 mm Hg. A common treatment effect was estimated
      across all fraction of inspired oxygen (Fio(2)) values, representing the average
      mean difference in oxygen uptake between oxygenated perfluorocarbon and saline
      solution, irrespective of the level of Fio(2). This average was 12.8 mm Hg (95%
      confidence interval, 7.4 to 18.2; p < 0.001). The most clinically relevant
      results occurred at an Fio(2) of 14%, resulting in a baseline mean Pao(2) of 39.4
      +/- 5.0 mm Hg with oxygenated saline solution perfusion, and a mean Pao(2) of
      55.3 +/- 7.6 mm Hg with oxygenated perfluorocarbon perfusion. This corresponded
      to an increase in arterial oxygen saturation from 73 to 89%. CONCLUSION: These
      results of our principle experiments demonstrate that the peritoneal cavity can
      be used for gas exchange and, in our model, yielded clinically relevant increases
      in systemic arterial oxygen levels. This technique may have the potential for the
      supportive care of patients dying from hypoxia in the setting of reversible lung
      injury.

PMID- 16899839
TI  - Management of postintubation tracheobronchial ruptures.
AB  - STUDY OBJECTIVES: To determine whether nonoperative management can be applied to
      iatrogenic postintubation tracheobronchial rupture (TBR). DESIGN: Prospective
      cohort study. PATIENTS AND INTERVENTIONS: Thirty consecutive patients with TBR
      complicating intubation between June 1993 and December 2005 entered the study.
      Patients not receiving mechanical ventilation at time of diagnosis were treated
      nonsurgically. Patients receiving mechanical ventilation who were judged operable
      underwent surgical repair, while nonoperable candidates had their TBR bridged by
      endotracheal tubes. RESULTS: Fifteen patients not requiring mechanical
      ventilation underwent simple conservative management. TBR length measured 3.85 +/
      1.46 cm (mean +/- SD). Eight TBRs showed full-thickness rupture with frank
      anterior intraluminal protrusion of the esophagus. In three patients, transient
      noninvasive positive pressure ventilatory support (NIV) was necessary. All
      lesions healed without sequelae. Two patients receiving mechanical ventilation
      underwent surgical repair and died. Thirteen patients receiving mechanical
      ventilation were considered at high surgical risk, and TBR bridging was attempted
      as salvage therapy. Complete bridging was achieved in five patients by simply
      advancing the endotracheal tube distal to the injury. Separate bilateral mainstem
      endobronchial intubation was necessary in six patients whose TBRs were too close
      to the carina. Nine of 13 patients (69%) treated with nonoperative therapy
      completely recovered. CONCLUSION: We conclude that conservative nonoperative
      therapy should be considered in patients with postintubation TBR who are
      breathing spontaneously, or when extubation is scheduled within 24 h from the
      time of diagnosis, or when continued ventilation is required to treat an
      underlying respiratory status. Surgical repair should be reserved for cases in
      which NIV or bridging the lesion is technically not feasible.

PMID- 16899840
TI  - Understanding cardiopulmonary resuscitation decision making: perspectives of
      seriously ill hospitalized patients and family members.
AB  - BACKGROUND: To improve communication and decision making related to
      cardiopulmonary resuscitation (CPR), a greater understanding of the perspectives
      of hospitalized patients with advanced diseases and their family members are
      needed. METHODS: In five Canadian hospitals, we administered a face-to-face
      questionnaire to older inpatients with end-stage cancer and advanced medical
      diseases and, where possible, to one of their family members, regarding
      information needs, the deliberation process, and their preferred decisional role.
      FINDINGS: A total of 440 of 569 patients (78%) and 160 of 176 available
      caregivers (91%) agreed to participate. Most patients (61%) had thought about
      what treatment they wanted if their heart stopped, few patients (11.3%) could
      describe more than two components of CPR, and only 2.7% of patients thought that
      the success rate of CPR was < 10%. A minority of patients (34%) had discussed CPR
      with their physician; 37% did not want to discuss their preferences with their
      doctor. Patients who felt that end-of-life issues were relevant to them were 5.5
      times more likely to want a discussion with the physician regarding resuscitation
      (odds ratio, 5.5; 95% confidence interval, 2.5 to 12.0). The preferred role in
      decision making was variable, but most patients (59.7%) and family members
      (81.6%) preferred some degree of shared decision making that included the family
      member. There were no significant differences between cancer and medical patients
      in their preferred decisional role. INTERPRETATION: Seriously ill hospitalized
      patients have poor knowledge about CPR, and variable preferences for deliberation
      and their role in the decision-making process regarding their treatment.
      Strategies that improve understanding of CPR and foster discussions that involve
      patients, family members, and physicians in the decision-making process may
      improve the quantity and quality of communication and decision making about CPR.

PMID- 16899841
TI  - Allergic rhinitis and sinusitis in asthma: differential effects on symptoms and
      pulmonary function.
AB  - BACKGROUND: Allergic rhinitis and sinusitis are frequently associated with
      asthma. The purpose of this study was to determine the impact of self-reported
      allergic rhinitis and sinusitis on lower airway disease in a large cohort of
      participants with well-characterized asthma. METHODS: A cohort study of
      participants in two trials of the American Lung Association-Asthma Clinical
      Research Centers: 2,031 asthmatics in the Safety of Inactivated Influenza Vaccine
      in Asthma in Adults and Children (SIIVA) trial and 488 asthmatics in the
      Effectiveness of Low Dose Theophylline as Add-on Treatment in Asthma (LODO)
      trial. At baseline, participants reported the presence of allergic rhinitis and
      sinusitis, and then lung function and asthma control were measured. During the
      trials, participants were monitored for asthma exacerbations. RESULTS: More than
      70% of participants reported either allergic rhinitis or sinusitis. Sinusitis was
      more common in female patients (odds ratio, 1.46 [SIIVA]), those with
      gastroesophageal reflux disease (odds ratio, 2.21 [SIIVA]), and those of white
      race (odds ratio, 1.53 [SIIVA]). Similar associations were seen for allergic
      rhinitis. LODO participants with allergic rhinitis and sinusitis had increased
      asthma symptoms and a trend toward more sleep disturbance. Participants with
      allergic rhinitis had higher baseline lung function than those without allergic
      rhinitis measured by peak flow (91.2% vs 95.8% in the SIIVA trial). Participants
      with sinusitis had similar lung function to those without sinusitis. Participants
      with and without allergic rhinitis had similar exacerbation rates. In the LODO
      trial only, participants with sinusitis had increased asthma exacerbations (5.68
      per patient per year vs 3.72 per patient per year). CONCLUSION: Allergic rhinitis
      and sinusitis are associated with more severe asthmatic symptoms and, in patients
      with poorly controlled asthma, more exacerbations but are not associated with low
      lung function.

PMID- 16899842
TI  - Is there a link between the qualitative descriptors and the quantitative
      perception of dyspnea in asthma?
AB  - BACKGROUND: There is no obvious link between qualitative descriptors and overall
      intensity of dyspnea during bronchoconstriction in patients with asthma. AIMS: To
      determine whether qualitative and quantitative perception of methacholine-induced
      bronchoconstriction independently contribute to characterizing clinically stable
      asthma. MATERIAL AND METHODS: We assessed changes in inspiratory capacity, and
      quantitative (by Borg scale) and qualitative (by a panel of eight dyspnea
      descriptors) sensations of dyspnea at 20 to 30% fall in FEV(1) during
      methacholine inhalation in 49 asthmatics. Furthermore, we calculated the level of
      perception of bronchoconstriction at 20% fall in FEV(1) (PB(20)). RESULTS:
      Descriptors selected by patients during methacholine inhalation allowed us to
      define three language subgroups: (1) chest tightness (subgroup A, n = 21); (2)
      work/effort (subgroup B, n = 7); and (3) both descriptors (subgroup C, n = 13).
      Eight of the 49 patients (subgroup D) were not able to make a clear-cut
      distinction among descriptors. The subgroups exhibited similar function at
      baseline and during methacholine inhalation. Most importantly, patients selected
      chest tightness to a greater extent (42.85%), and work/effort (14.3%) and both
      descriptors (26.5%) to a lesser extent at the lowest level of bronchoconstriction
      (FEV(1) fall < 10%) as at 20% fall in FEV(1). Thirty-two patients were
      normoperceivers (PB(20) > or = 1.4 to < 5 arbitrary units [au]), 7 patients were
      hyperperceivers (PB(20) > or = 5 au), and 10 patients were hypoperceivers (PB(20)
      < 1.4 au). Language subgroups were equally distributed across the perceiver
      subgroups. CONCLUSIONS: In patients with clinically stable asthma, PB(20) and
      language of dyspnea independently contribute to defining the condition of the
      disease. However, the possibility that this independence may be due to a beta
      error should be taken into account.

PMID- 16899843
TI  - Allergic bronchopulmonary aspergillosis: lessons from 126 patients attending a
      chest clinic in north India.
AB  - AIMS AND OBJECTIVES: To describe the experience of screening patients with asthma
      for allergic bronchopulmonary aspergillosis (ABPA) presenting to a chest clinic.
      The clinical, serologic, radiologic, and treatment aspects including outcome of
      ABPA are also described. METHODS: All consecutive patients with asthma presenting
      to the chest clinic over a period of 2 years were screened with an Aspergillus
      skin test. Patients who were found to be positive were further investigated for
      ABPA. Patients were also arbitrarily classified as ABPA-seropositive (ABPA-S),
      ABPA with central bronchiectasis (ABPA-CB), and ABPA-CB with other radiologic
      findings (ABPA-CB-ORF) based on the high-resolution CT findings. RESULTS: Five
      hundred sixty-four patients were screened using an Aspergillus skin test; 223
      patients (39.5%) were found to be positive, and ABPA was diagnosed in 126
      patients (27.2%). There were 34 patients (27%) with ABPA-S, 42 patients with ABPA
      CB, and 50 patients with ABPA-CB-ORF. Fifty-nine patients (46.8%) had received
      antitubercular therapy in the past. The vast majority of patients had
      bronchiectasis at presentation to our hospital. High-attenuation mucous impaction
      was noted in 21 patients (16.7%). There was no significant difference between the
      stages of ABPA and the duration of illness, the severity of asthma, and the
      serologic findings (ie, absolute eosinophil count, IgE levels [total] and IgE
      levels [for Aspergillus fumigatus]). The median duration of follow-up was 13
      months (range, 9 to 38 months). All patients went into "remission" at 6 weeks.
      Twenty-five patients had a "relapse" during the course of their treatment. One
      hundred nine patients had "complete remission," 17 patients were classified as
      having "glucocorticoid-dependent ABPA," and 7 patients were classified as having
      "end-stage ABPA." CONCLUSIONS: There is a high prevalence of ABPA in asthmatic
      patients presenting at our hospital. The disease entity is still underrecognized
      in India; the vast majority of patients have bronchiectasis at presentation, and
      almost half are initially misdiagnosed as having pulmonary tuberculosis. There is
      a need to redefine the definitions of ABPA and the optimal dose/duration of
      glucocorticoid therapy. This study reinforces the need for the routine screening
      of asthmatic patients with an Aspergillus skin test.

PMID- 16899845
TI  - Quality of occupational history assessments in working age adults with newly
      diagnosed asthma.
AB  - BACKGROUND: Approximately 10 to 15% of new-onset asthma in adults is attributable
      to occupational exposure. The occupational history is the most important
      instrument in the diagnosis of occupational asthma (OA). STUDY OBJECTIVES: To
      assess the quality of occupational histories obtained by health-care providers
      and to measure the prevalence of clinician-diagnosed OA in a population at
      elevated risk for OA. SETTING: An academic US Department of Veteran Affairs
      medical center. STUDY POPULATION: One hundred ninety-seven adults (age range, 18
      to 55 years) with newly diagnosed asthma who had completed pulmonary function
      testing (PFT) and a structured respiratory health questionnaire. MEASUREMENTS: We
      conducted a structured retrospective comparison of occupational respiratory
      health history documented by clinicians with data documented by patients on a
      structured questionnaire. We analyzed PFT results to assess physiologic
      impairment. We also conducted a structured examination of the actions taken by
      health-care providers based on their occupational history assessments. RESULTS:
      Patient self-reports of respiratory exposures and symptoms were common. A job
      title was documented by one or more clinicians in 75% of patient medical records.
      Additional occupational history data were charted much less frequently. A
      diagnosis of OA was made in only 2% of patients. Clinical action to address OA
      was documented for only one patient. CONCLUSIONS: Clinicians who manage adults
      with newly diagnosed asthma take incomplete occupational histories. We detected
      discordance between the occupational exposure histories documented by patients
      and those charted by clinicians. OA may go unrecognized and possibly undermanaged
      by clinicians.

PMID- 16899846
TI  - Health-care use among Puerto Rican and African-American children with asthma.
AB  - STUDY OBJECTIVES: To compare the rates of emergency department (ED) visits,
      hospitalizations, hospital days, and outpatient clinic visits for asthma among
      children in two ethnic minority groups that are disproportionately affected by
      asthma (Puerto Ricans and African Americans). STUDY DESIGN: This cross-sectional
      study was part of an asthma intervention program in Hartford, CT, in which 6,554
      children were screened for asthma by primary care providers using a parental
      survey. Medicaid and the supplementary State Children's Health Insurance Plan
      data about health-care utilization for asthma were obtained for each child for
      the 12 months preceding completion of the screening survey. RESULTS: Among 2,304
      children in whom asthma had been diagnosed, Puerto Ricans had more severe asthma
      than African Americans. In analyses adjusted for asthma severity and other
      potential confounders, Puerto Rican children had more clinic visits for asthma
      (rate ratio [RR], 1.31; 95% confidence interval [CI], 1.12 to 1.53) but spent
      fewer days in the hospital for asthma (RR, 0.36; 95% CI, 0.24 to 0.53) than
      African-American children. There were no differences in the rates of ED visits or
      hospitalizations between the two groups. CONCLUSIONS: Puerto Rican children had
      more severe asthma but were less likely than African-American children to have
      prolonged hospitalizations for asthma. This finding may be due to the frequent
      clinic visits for asthma made by Puerto Rican children. Further research is
      needed to understand the cultural factors that contribute to different approaches
      to health-care utilization among ethnic minorities.

PMID- 16899844
TI  - Association between nonspecific airway hyperresponsiveness and Arg16Gly beta2
      adrenergic receptor gene polymorphism in asymptomatic healthy Japanese subjects.
AB  - BACKGROUND: Nonspecific airway hyperresponsiveness (AHR), a cardinal feature of
      asthma, is thought to result from several genetic and environmental factors.
      Asymptomatic AHR in nonasthmatic healthy subjects might be a risk factor for the
      development of asthma. Genetic variations in codons 16 and 27 of the human
      beta(2)-adrenergic receptor (beta(2)-AR) alter receptor function in vitro and are
      associated with various asthma-related phenotypes, including asthma severity and
      AHR. To date, however, few reports have examined the impact of beta(2)-AR gene
      polymorphism on AHR in asymptomatic healthy subjects. OBJECTIVE: To determine
      whether polymorphism of the beta(2)-AR gene (Arg16Gly and Gln27Glu) might
      influence nonspecific AHR in asymptomatic healthy Japanese subjects. DESIGN AND
      PARTICIPANTS: A cohort of 120 asymptomatic healthy subjects was analyzed using a
      stepwise linear regression model. Nonspecific airway responsiveness was measured
      using a continuous methacholine inhalation method (Astograph; Chest; Tokyo,
      Japan). We used values of the cumulative dose of inhaled methacholine measured at
      the inflection point at which respiratory conductance starts to decrease (Dmin)
      as an index of AHR. Genotyping to identify polymorphisms at codons 16 and 27 was
      conducted using an assay combining kinetic real-time quantitative polymerase
      chain reaction with allele-specific amplification. RESULTS: The Gly16Gly genotype
      was associated with lower Dmin values. The log Dmin value of asymptomatic healthy
      subjects carrying the Arg16 allele (Arg16/Arg or Arg16/Gly, n = 90) was 1.09 +/-
      0.56 (mean +/- SD), while those homozygous for the Gly16 allele (n = 30) yielded
      a log Dmin value of 0.85 +/- 0.56 (p < 0.05). CONCLUSION: This study indicates
      that a specific beta(2)-AR polymorphism at codon 16 might be a genetic
      determinant of AHR, as judged by methacholine-induced bronchoconstriction in
      asymptomatic healthy subjects.

PMID- 16899848
TI  - Lung structure abnormalities, but normal lung function in pediatric
      bronchiectasis.
AB  - BACKGROUND: Bronchiectasis is not considered to be uncommon in children anymore.
      The relationship between pulmonary function and severity of bronchiectasis is
      still controversial. STUDY OBJECTIVES: To assess the extent and severity of
      bronchiectasis through high-resolution CT (HRCT) scan score, and to correlate it
      with clinical, microbiological, and functional data. PATIENTS AND METHODS: Forty
      three white children with HRCT-diagnosed bronchiectasis were studied.
      Bronchiectasis extent, bronchial wall thickening severity, and bronchial wall
      dilatation severity were evaluated using the Reiff score. Clinical,
      microbiological, and spirometry results were related to total HRCT scan score and
      to subscores as well. RESULTS: The percentages of affected lobes were as follows:
      right lower lobe, 65%; middle lobe, 56%; left lower lobe, 51%; right upper lobe,
      37%; lingula, 30%; and left upper lobe, 30% (chi(2) = 18.4; p = 0.002). The mean
      (+/- SEM) HRCT score was 20 +/- 2.6. Total score or subscores of bronchiectasis
      extent, bronchial wall thickening severity, and bronchial wall dilatation
      severity were not significantly related to FEV(1) and FVC. Seventy-four percent
      of patients had asthma. The age at the onset of cough correlated with age at the
      time of the HRCT scan (p = 0.004) and with the presence of asthma (p = 0.01).
      Positive findings of deep throat or sputum cultures were found more frequently in
      atopic patients (p = 0.02) and asthmatic (p < 0.01) patients, and in children who
      were < 2 years of age at the onset of cough (p < 0.01). CONCLUSIONS: Normal lung
      function may coexist with HRCT scan abnormalities and does not exclude damage to
      the bronchial structure. Pulmonary function is not an accurate method for
      assessing the severity of lung disease in children with bronchiectasis.

PMID- 16899847
TI  - Orthopnea and tidal expiratory flow limitation in chronic heart failure.
AB  - BACKGROUND: Tidal expiratory flow limitation (FL) is common in patients with
      acute left heart failure and contributes significantly to orthopnea. Whether
      tidal FL exists in patients with chronic heart failure (CHF) remains to be
      determined. PURPOSES: To measure tidal FL and respiratory function in CHF
      patients and their relationships to orthopnea. METHODS: In 20 CHF patients (mean
      [+/- SD] ejection fraction, 23 +/- 8%; mean systolic pulmonary artery pressure
      [sPAP], 46 +/- 18 mm Hg; mean age, 59 +/- 11 years) and 20 control subjects who
      were matched for age and gender, we assessed FL, Borg score, spirometry, maximal
      inspiratory pressure (Pimax), mouth occlusion pressure 100 ms after the onset of
      inspiratory effort (P(0.1)), and breathing pattern in both the sitting and supine
      positions. The Medical Research Council score and orthopnea score were also
      determined. RESULTS: In the sitting position, tidal FL was absent in all patients
      and healthy subjects. In CHF patients, Pimax was reduced, and ventilation and
      P(0.1)/Pimax ratio was increased relative to those of control subjects. In the
      supine position, 12 CHF patients had FL and 18 CHF patients claimed orthopnea
      with a mean Borg score increasing from 0.5 +/- 0.7 in the sitting position to 2.7
      +/- 1.5 in the supine position in CHF patients. In contrast, orthopnea was absent
      in all control subjects. The FL patients were older than the non-FL patients
      (mean age, 63 +/- 8 vs 53 +/- 12 years, respectively; p < 0.03). In shifting from
      the seated to the supine position, the P(0.1)/Pimax ratio and the effective
      inspiratory impedance increased more in CHF patients than in control subjects.
      The best predictors of orthopnea in CHF patients were sPAP, supine Pimax, and the
      percentage change in inspiratory capacity (IC) from the seated to the supine
      position (r(2) = 0.64; p < 0.001). CONCLUSIONS: In sitting CHF patients, tidal FL
      is absent but is common supine. Supine FL, together with increased respiratory
      impedance and decreased inspiratory muscle force, can elicit orthopnea, whom
      independent indicators are sPAP, supine Pimax and change in IC percentage.

PMID- 16899849
TI  - Aerosol therapy by pressured metered-dose inhaler-spacer in sleeping young
      children: to do or not to do?
AB  - One third of young children are distressed during inhalation therapy. It has been
      suggested that administration during sleep could be a good alternative for these
      children. A laboratory study in our department using an infant upper airway model
      showed significantly higher lung doses from a pressured metered-dose inhaler
      (pMDI)-spacer for sleep-breathing patterns compared with wake-breathing patterns.
      OBJECTIVE: We set up a daily life study to investigate the feasibility of aerosol
      administration by means of pMDI-spacer in sleeping young children. DESIGN: Over a
      period of 3 weeks, 30 children (age range, 6 to 23 months) with recurrent wheeze
      daily inhaled 1 puff of budesonide aerosol (200 mug) while awake and 1 puff
      during sleep. Filters positioned between the chamber and the facemask trapped the
      budesonide aerosol. Parents scored the child's asthma symptoms, degree of
      cooperation, and feasibility of administration on diary cards. RESULTS: In 69% of
      the sleep administrations, the children woke up, and in 75% of these cases the
      children were distressed. The mean filter dose (expressed as the percentage of
      the nominal dose) while awake was 47%, and during sleep it was 16% (p = 0.007).
      The median within-subject dose variability while awake was 50%, and during sleep
      it was 110% (p = 0.007). CONCLUSION: Aerosol administration by means of pMDI
      spacer during sleep offers no advantage and is not a feasible treatment option in
      most young children.

PMID- 16899850
TI  - Interpreting periodic lung function tests in individuals: the relationship
      between 1- to 5-year and long-term FEV1 changes.
AB  - STUDY OBJECTIVE: Spirometry is performed to monitor lung health, but variability
      between tests can hinder recognition of excessive FEV(1) declines. We sought to
      describe the relationship between FEV(1) changes over 1 to 5 years and FEV(1)
      declines over longer terms, using 21,821 test results from 1,884 workers who
      participated in an annual health monitoring program at a chemical plant between
      1973 and 2003. METHODS: Test results from workers with five or more valid results
      over > or = 10 years were included in our analysis (mean initial worker age, 35
      years; range, 18 to 62 years; 91% male; 35% current smokers and 41% nonsmokers).
      For each worker, long-term FEV(1) slopes (milliliters per year) were calculated
      by simple linear regression using all available results and compared to changes
      in FEV(1) between two tests over 1 to 5 years, expressed in both milliliters and
      percentage of initial value. RESULTS: Long-term (mean, 18 years; range, 10 to 30
      years) slopes averaged - 29.1 mL/yr (- 27, - 29, and - 37 mL/yr for male never
      smokers, former smokers, and current smokers, and - 20, - 26, and - 27 mL/yr for
      female never-smokers, former smokers, and current smokers, respectively).
      Excessive short-term and long-term declines were defined by lower fifth
      percentile values. Individuals with abnormal short-term declines were found to be
      3 to 18 times more likely to ultimately show excessive long-term declines; with
      the strength of the association increasing with the length of the short-term
      testing interval. Better test operating characteristics resulted if abnormal
      short-term FEV(1) change was based on percentage change (ie, percentage per year)
      rather than absolute change (ie, milliliters per year). CONCLUSIONS: Our findings
      provide guidance for interpreting periodic spirometry results from individuals
      exposed to respiratory hazards.

PMID- 16899851
TI  - Impact of a physical rehabilitation program on the respiratory function of
      adolescents with idiopathic scoliosis.
AB  - BACKGROUND: Idiopathic adolescent scoliosis (AIS) causes not only spinal
      deformities but rib cage abnormalities that lead to abnormal volumes and
      pulmonary capacity on pulmonary function testing (PFT). The objective of this
      study was to analyze the impact of a physical rehabilitation program on
      respiratory function in surgical patients with AIS. METHODS: From October 2003 to
      October 2004, a total of 34 patients (age range, 10 to 18 years) presenting with
      AIS and a thoracic curvature between 45 degrees and 88 degrees were studied
      prospectively at a tertiary academic hospital. The patients underwent clinical
      and radiographic evaluations of the vertebral deformity, chest radiographs, PFT,
      evaluation of peak expiratory flow, and 6-min walk tests (6MWTs) before and after
      joining a physical rehabilitation program for 4 months. RESULTS: An improvement
      in FVC, inspiratory capacity, FEV(1), expiratory reserve volume, and performance
      assessed by 6MWT were observed after rehabilitation. CONCLUSIONS: Global
      conditioning improved after the rehabilitation program. This was expressed by
      both PFT and 6MWT results.

PMID- 16899852
TI  - Cardiovascular function following surgical repair of pectus excavatum: a
      metaanalysis.
AB  - BACKGROUND: Despite numerous published reports, there is no consensus in the
      literature as to whether the surgical repair of the pectus excavatum improves
      cardiovascular function. As a result, it has been suggested that correction
      should be considered a cosmetic procedure, and therefore, many health insurance
      companies have questioned whether the repair of the pectus excavatum improves
      cardiovascular function and thus are reluctant to authorize the procedure. The
      purpose of this study was to apply metaanalysis methodology to generate a
      quantitative synthesis of the effects of surgical repair on cardiovascular
      function and to test the hypothesis that surgical repair of the pectus excavatum
      results in significant improvements in cardiovascular function. METHODS: Studies
      were retrieved via computerized literature searches, cross-referencing from
      original and review articles, and a review of the reference list by a recognized
      authority in the area of pectus excavatum repair. The inclusion criteria were as
      follows: (1) reporting quantitative measures of preoperative and postoperative
      cardiovascular function; (2) published in the English language; (3) indexed
      between January 1960 and May 2005; (4) reporting the duration between which
      preoperative and postoperative assessments were conducted; and (5) describing the
      cardiovascular assessment procedures. RESULTS: A comprehensive search of the
      literature identified eight studies that met all of the inclusion criteria. These
      studies, representing 169 pectus excavatum patients, were used for the
      metaanalysis. Random-effects modeling yielded a mean weighted effect size (ES)
      for cardiovascular function that was statistically significant (ES, 0.59; 95%
      confidence interval, 0.25 to 0.92; p = 0.0006). CONCLUSIONS: The findings of the
      present study indicated that surgical repair of the pectus excavatum
      significantly improves cardiovascular function and contradicts arguments that
      surgical repair is primarily cosmetic yielding minimal physiologic improvement.

PMID- 16899853
TI  - Cardiorespiratory fitness and short-term complications after bariatric surgery.
AB  - BACKGROUND: Morbid obesity is associated with reduced functional capacity,
      multiple comorbidities, and higher overall mortality. The relationship between
      complications after bariatric surgery and preoperative cardiorespiratory fitness
      has not been previously studied. METHODS: We evaluated cardiorespiratory fitness
      in 109 patients with morbid obesity prior to laparoscopic Roux-en-Y gastric
      bypass surgery. Charts were abstracted using a case report form by reviewers
      blinded to the cardiorespiratory evaluation results. RESULTS: The mean age (+/-
      SD) was 46.0 +/- 10.4 years, and 82 patients (75.2%) were female. The mean body
      mass index (BMI) was 48.7 +/- 7.2 (range, 36.0 to 90.0 kg/m(2)). The composite
      complication rate, defined as death, unstable angina, myocardial infarction,
      venous thromboembolism, renal failure, or stroke, occurred in 6 of 37 patients
      (16.6%) and 2 of 72 patients (2.8%) with peak oxygen consumption (Vo(2)) levels <
      15.8 mL/kg/min or > 15.8 mL/kg/min (lowest tertile), respectively (p = 0.02).
      Hospital lengths of stay and 30-day readmission rates were highest in the lowest
      tertile of peak Vo(2) (p = 0.005). There were no complications in those with BMI
      < 45 kg/m(2) or peak Vo(2) > or= 15.8 mL/kg/min. Multivariate analysis adjusting
      for age and gender found peak Vo(2) was a significant predictor of complications:
      odds ratio, 1.61 (per unit decrease); 95% confidence interval, 1.19 to 2.18 (p =
      0.002). CONCLUSIONS: Reduced cardiorespiratory fitness levels were associated
      with increased, short-term complications after bariatric surgery.
      Cardiorespiratory fitness should be optimized prior to bariatric surgery to
      potentially reduce postoperative complications.

PMID- 16899854
TI  - Prevalence of hypothyroidism and Graves disease in sarcoidosis.
AB  - BACKGROUND: The association of sarcoidosis (S) and thyroid autoimmunity has been
      reported by several studies in a wide range of variability. The aim of our study
      was to evaluate the prevalence of clinical and subclinical thyroid disorders in
      patients with S vs gender-matched and age-matched control subjects. METHODS:
      Thyroid hormones and antithyroid antibodies, thyroid ultrasonography and fine
      needle aspiration were performed in 111 patients with S who had been
      consecutively referred to the Respiratory Pathophysiology Section of the
      University of Pisa, and the results were compared to 333 gender-matched and age
      matched control subjects from the same geographic area. RESULTS: The odds ratio
      for subclinical hypothyroidism for female patients with S vs control subjects was
      2.7 (95% confidence interval [CI], 1.3 to 5.9); for anti-thyroid peroxidase
      antibody titer (AbTPO) positivity, 2.2 (95% CI, 1.2 to 3.9); and for thyroid
      autoimmunity, 1.9 (95% CI, 1.1 to 3.2). The mean values of thyroid-stimulating
      hormone and AbTPO were higher in female S patients than in control subjects (p <
      0.01). A significantly higher prevalence of clinical hypothyroidism (four
      patients) and Graves disease (three patients) was observed in female S patients
      than in control subjects (none; p = 0.005 and 0.0026, respectively). Two cases of
      papillary thyroid cancer were detected in S patients. No significant difference
      between S patients and control subjects was detected for free triiodothyronine
      and thyroxine, antithyroglobulin autoantibodies, thyroid volume and nodularity,
      and subclinical hyperthyroidism. CONCLUSIONS: Thyroid function, AbTPO antibodies,
      and ultrasonography should be tested as part of the clinical profile in female S
      patients. Subjects who are at high risk (female subjects, those with positive
      AbTPOs, and those with hypoechoic and small thyroid) should have thyroid function
      follow-up and appropriate treatment in due course.

PMID- 16899855
TI  - Chest ultrasonography in lung contusion.
AB  - STUDY OBJECTIVE: Despite the high prevalence of chest trauma and its high
      morbidity, lung contusion (LC) often remains undiagnosed in the emergency
      department (ED). The present study investigates the possible clinical
      applicability of chest ultrasonography for the diagnosis of LC in the ED in
      comparison to radiography and CT. MATERIALS AND METHODS: One hundred twenty-one
      patients admitted to the ED for blunt chest trauma were investigated using
      ultrasonography by stage III longitudinal scanning of the anterolateral chest
      wall to detect LC. Data were retrospectively collected in an initial series of
      109 patients (group 1) and prospectively in the next 12 patients (group 2). All
      patients who presented with pneumothorax were excluded. After the ultrasound
      study, all patients were submitted to chest radiography (CXR) and CT. The
      sonographic patterns indicative of LC included the following: (1) the
      alveolointerstitial syndrome (AIS) [defined by increase in B-line artifacts]; and
      (2) peripheral parenchymal lesion (PPL) [defined by the presence of C-lines:
      hypoechoic subpleural focal images with or without pleural line gap]. RESULTS:
      The diagnosis of LC was established by CT scan in 37 patients. If AIS is
      considered, the sensitivity of ultrasound study was 94.6%, specificity was 96.1%,
      positive and negative predictive values were 94.6% and 96.1%, respectively, and
      accuracy was 95.4%. If PPL is alternatively considered, sensitivity and negative
      predictive values drop to 18.9% and 63.0%, respectively, but both specificity and
      positive predictive values increased to 100%, with an accuracy of 65.9%.
      Radiography had sensitivity of 27% and specificity of 100%. CONCLUSIONS: Chest
      ultrasonography can accurately detect LC in blunt trauma victims, in comparison
      to CT scan.

PMID- 16899856
TI  - Prevalence of vertebral fractures in adults with cystic fibrosis and their
      relationship to bone mineral density.
AB  - STUDY OBJECTIVES: The objectives of this study were to determine the prevalence
      of morphometric vertebral fractures in a large cohort of adult cystic fibrosis
      (CF) patients, and to examine the association between fractures and bone mineral
      density (BMD). DESIGN: Cross-sectional retrospective study. SETTING: A tertiary
      care academic hospital. PATIENTS: Adult CF patients who had undergone BMD testing
      and chest radiography within 1 month of each other. MEASUREMENTS AND RESULTS: BMD
      was measured by dual-energy x-ray absorptiometry (DXA) at the lumbar spine (LS)
      and femoral neck (FN). Vertebral fractures were diagnosed using lateral chest
      radiographs. Several clinical and biochemical variables were assessed as
      correlates. Sixty subjects (36%) had z scores between -1.0 and -2.5, and 15
      subjects (9%) had z scores of < -2.5. Twelve patients (7.2%) had 19 morphometric
      fractures. The mean BMD at the LS was 1.266 g/cm(2) in the fracture group and
      1.112 g/cm(2) in the nonfracture group (p = 0.0002). The mean BMD at the FN was
      1.129 g/cm(2) in the fracture group and 0.987 g/cm(2) in the nonfracture group (p
      = 0.0006). Both FEV(1) and body mass index were significantly associated with BMD
      at both the LS and the FN. CONCLUSION: Seven percent of adult patients with CF
      had vertebral fractures as determined by morphometry. Subjects in the fracture
      group had both clinically and statistically higher BMD as measured by DXA. Our
      findings raise the intriguing possibility that BMD may not be useful in
      identifying CF patients with fractures.

PMID- 16899857
TI  - Thrombotic arteriopathy and anticoagulation in pulmonary hypertension.
AB  - The role of thrombotic arteriopathy in the pathophysiology of idiopathic
      pulmonary arterial hypertension (IPAH) and the use of anticoagulants in the
      treatment of IPAH are currently controversial issues. This article reviews the
      evidence for a role of vascular thrombosis in the pathophysiology of IPAH. There
      is sufficient biological rationale to support the notion that thrombotic
      arteriopathy is an important pathophysiologic feature of pulmonary arterial
      hypertension (PAH) and that its progression materially contributes to disease
      progression. To date, the data from observational studies suggest that
      anticoagulation with warfarin is an effective intervention in patients with IPAH.
      Its efficacy in other causes of PAH remains speculative.

PMID- 16899858
TI  - Diffuse alveolar damage: uncommon manifestation of pulmonary involvement in
      patients with connective tissue diseases.
AB  - BACKGROUND: Diffuse alveolar damage (DAD) is a relatively common finding on
      surgical lung biopsy and can result from a variety of causes. METHODS: We studied
      nine consecutive patients with connective tissue disease (CTD) and DAD diagnosed
      on surgical lung biopsy to examine this association and clinical implications.
      RESULTS: The median age was 63 years (range, 35 to 76 years), and seven of the
      patients were women (78%). Underlying CTDs included rheumatoid arthritis in five
      patients, polymyositis in two patients, and one patient each with systemic
      sclerosis and mixed CTD. In seven patients (78%), CTD had been diagnosed before
      the onset of DAD; six of these patients had a preexisting interstitial lung
      disease (ILD) related to their CTD. DAD was the presenting manifestation leading
      to a new CTD diagnosis in two patients (22%). CT of the chest revealed ground
      glass opacities and/or consolidation bilaterally with or without honeycombing. In
      all patients, surgical lung biopsy revealed DAD for which no cause could be
      identified other than the underlying CTD. Seven patients (78%) were receiving
      mechanical ventilatory support at the time of the surgical lung biopsy. Four
      patients (44%) survived to hospital discharge and included one patient with
      preexisting ILD and all three patients without chronic ILD. CONCLUSION: We
      conclude that DAD can complicate the clinical course of patients with CTD-related
      chronic ILD, or can occasionally occur as a presenting manifestation of CTDs.
      When DAD occurs in patients with CTDs, the outcome appears to be worse for those
      with preexisting chronic ILD compared to those without ILD.

PMID- 16899859
TI  - A virtual bronchoscopic navigation system for pulmonary peripheral lesions.
AB  - STUDY OBJECTIVES: We performed ultrathin bronchoscopy for pulmonary peripheral
      lesions using a system that displays virtual bronchoscopy (VB) images to the
      lesion simultaneously with actual images and navigates the bronchoscope to the
      target bronchus. We then evaluated the system with regard to its usefulness and
      problems. DESIGN: A pilot study. SETTING: A tertiary teaching hospital. PATIENTS:
      The subjects were consecutive patients with small pulmonary peripheral lesions (<
      or = 30 mm). INTERVENTIONS: Using this system, the rotation, advancement, and
      retreat of VB images were possible, and the bronchus into which the bronchoscope
      was to be advanced was displayed. VB images were displayed along with actual
      images, and the ultrathin bronchoscope was advanced to the target bronchus under
      direct vision. Under CT and radiographic fluoroscopy, a pair of forceps was
      inserted into the lesion via the bronchoscope. Thin-section CT images were
      obtained; after confirming the advancement of the bronchoscope into the target
      bronchus and the arrival of the forceps at the lesion, a biopsy was performed.
      RESULTS: Study subjects included 37 patients with 38 lesions. VB images to a
      median of the sixth- (third- to ninth-) order bronchi could be produced. Using
      this system, the ultrathin bronchoscope could be advanced into the planned route
      for 36 of the 38 lesions (94.7%). The system was used for a median of 2.6 min,
      and the median examination time was 24.9 min. The biopsy forceps could be
      advanced to the lesion in 33 of the 38 lesions (86.8%), and diagnosis was
      possible for 31 lesions (81.6%). CONCLUSIONS: This navigation system is useful
      for ultrathin bronchoscopy for pulmonary peripheral lesions.

PMID- 16899860
TI  - Proteomics in pulmonary medicine.
AB  - Proteomics is the study of the entire protein complement of the genome (the
      proteome) in a biological system. Proteomic studies require a multidisciplinary
      approach and have only been practical with the convergence of technical and
      methodologic improvements including the following: advances in mass spectrometry
      and genomic sequencing that now permit the identification and relative
      quantization of small amounts (femtomole) of nearly any single protein; new
      methods in gel electrophoresis that allow the detection of subtle changes in
      protein expression, including posttranslational modifications; automation and
      miniaturization that permit high-throughput analysis of clinical samples; and new
      bioinformatics and computational methods that facilitate analysis and
      interpretation of the abundant data that are generated by proteomics experiments.
      This convergence makes proteomics studies practical for pulmonary researchers
      using BAL fluid, lung tissue, blood, and exhaled breath condensates, and will
      facilitate the research of complex, multifactorial lung diseases such as acute
      lung injury and COPD. This review describes how proteomics experiments are
      conducted and interpreted, their limitations, and how proteomics has been used in
      clinical pulmonary medicine.

PMID- 16899861
TI  - Intrapulmonary bronchogenic cyst and cerebral gas embolism in an aircraft flight
      passenger.
AB  - Although it is estimated that > 1 billion passengers travel by air worldwide each
      year, the incidence of in-flight emergencies is low. However, due to
      nonstandardized reporting requirements for in-flight medical emergencies, the
      true incidence of pulmonary barotrauma in airplane passengers is unknown. We
      describe the case of a passenger with an asymptomatic intrapulmonary cyst in whom
      a severe case of cerebral gas embolism developed during an aircraft flight. The
      decrease in ambient pressure during the aircraft climb resulted in expansion of
      the cyst volume based on Boyle's law (pressure x volume = constant). Due to the
      cyst expansion, we believe tears in the wall led to the leakage of air into the
      surrounding vessels followed by brain gas emboli. Adult patients with
      intrapulmonary cysts should be strongly considered for cyst resection or should
      at least be advised to abstain from activities leading to considerable changes in
      ambient pressure.

PMID- 16899862
TI  - Successful use of recombinant factor VII in massive hemoptysis due to community
      acquired pneumonia.
AB  - Recombinant activated factor VII (rFVIIa) is a powerful hemostatic agent
      developed for use in hemophilia. It has been used increasingly in life
      threatening hemorrhage in a variety of other settings in which conventional
      medical or surgical therapy is unsuccessful. This report describes the successful
      use of rFVIIa for pulmonary hemorrhage due to a focal bleeding source in a
      regional hospital where bronchial artery embolization or surgery were not
      available. rFVIIa may be a useful temporizing measure in the unstable patient
      with pulmonary hemorrhage without coagulopathic bleeding when conventional
      treatment is not immediately available.

PMID- 16899864
TI  - Pleural malignant solitary fibrous tumor with sarcomatous overgrowth showing
      PDGFRbeta mutation.
AB  - Pleural malignant solitary fibrous tumors (SFTs) are uncommon, and little is
      known about their histogenesis and molecular features. We report a case of
      pleural SFT with sarcomatous overgrowth that showed expression for PDGFRbeta and
      a missense mutation on exon 18 of the PDGFRbeta gene. The involvement of the
      PDGFRbeta gene in SFT is compatible with a pericytic derivation, also supporting
      a possible role of this tyrosine kinase in malignant transformation and in the
      adoption of novel molecular therapies.

PMID- 16899863
TI  - Stridor in Crohn disease and the use of infliximab.
AB  - Extraintestinal manifestations of Crohn disease are well recognized. Upper airway
      obstruction is a very rare but important complication that usually responds to
      high-dose steroids. We report a case of Crohn disease initially presenting with
      respiratory symptoms and subsequently resulting in acute severe upper airway
      obstruction, which failed to respond to steroids but dramatically responded to
      the first documented use of infliximab in this context.

PMID- 16899865
TI  - Management of perioperative myocardial infarction in noncardiac surgical
      patients.
AB  - Perioperative myocardial infarction (PMI) is a major cause of morbidity and
      mortality in patients undergoing noncardiac surgery. The incidence of PMI varies
      depending on the method used for diagnosis and is likely to increase as the
      population ages. Studies have examined different methods for prevention of
      myocardial infarction (MI), including the use of perioperative beta-blockers,
      alpha(2)-agonists, and statin therapy. However, few studies have focused on the
      treatment of PMI. Current therapy for acute MI generally involves anticoagulation
      and antiplatelet therapy, raising the potential for surgical site hemorrhage in
      this population. This article reviews the possible mechanisms, diagnosis, and
      treatment options for MI in the surgical setting. We also suggest algorithms for
      treatment.

PMID- 16899866
TI  - Diagnosis and treatment of ventilator-associated pneumonia.
AB  - Ventilator-associated pneumonia (VAP) is the most common nosocomial infection in
      the ICU. Patients who acquire VAP have higher mortality rates and longer ICU and
      hospital stays. Because there are other potential causes of fever, leukocytosis,
      and pulmonary infiltrates, clinical diagnostic criteria are overly sensitive in
      the diagnosis of VAP. Employing quantitative cultures of bronchopulmonary
      secretions in the diagnostic algorithm leads to less antibiotic use and probably
      to lower mortality. With respect to microbiologic diagnosis, it is not clear that
      the use of a particular sampling method (bronchoscopic or nonbronchoscopic), when
      quantitatively cultured, is associated with better outcomes. Delayed
      administration of adequate antibiotic therapy is linked to an increased mortality
      rate. Hence, the focus of initial antibiotic therapy should be to rapidly provide
      antibiotic coverage for all likely pathogens and to then narrow or focus the
      antibiotic spectrum based on the results of quantitative cultures. Eight days of
      antibiotic therapy appears equivalent to 15 days of therapy except when treating
      nonlactose-fermenting Gram-negative organisms. In this latter situation, longer
      treatment durations appear to reduce the risk of recrudescence after
      discontinuation of antibiotic therapy. A guideline-based approach using the local
      hospital or ICU antibiogram can increase the likelihood that adequate initial
      antibiotic therapy is used and reduce the overall use of antibiotics and the
      associated selection pressure for multidrug-resistant organisms.

PMID- 16899867
TI  - Parasomnias: clinical features and forensic implications.
AB  - Parasomnias are undesirable behavioral or experiential phenomena arising from the
      sleep period. Once felt to be a unitary phenomenon, it is now clear that a wide
      variety of sleep disorders are capable of resulting in complex behaviors arising
      during sleep. The most common are disorders of arousal and rapid eye movement
      sleep disorder. Less common conditions include nocturnal seizures and psychogenic
      dissociative states. Malingering and Munchausen syndrome by proxy, while they are
      not actually parasomnias, may masquerade as parasomnias. Careful clinical and
      sleep laboratory evaluation can usually provide an accurate diagnosis with
      effective therapeutic implications. Due to the potential forensic implications,
      sleep medicine specialists may be asked to participate in legal proceedings
      resulting from sleep-related violence. An awareness of the spectrum of such
      behaviors, and their clinical and legal evaluation, is becoming more important in
      the practice of sleep medicine.

PMID- 16899868
TI  - A 19-year-old pregnant woman with a skin lesion and respiratory failure.

PMID- 16899869
TI  - Acute tachypnea during mechanical ventilation in a 62-year-old man with multiple
      myeloma involving the spinal cord.

PMID- 16899870
TI  - Graphs.
AB  - Two rules of good graphs are presented and explicated.

PMID- 16899871
TI  - Magnitude of bronchoprotection of albuterol vs methacholine: relationship to
      baseline airway caliber.

PMID- 16899872
TI  - Diet and exercise-induced bronchoconstriction.

PMID- 16899873
TI  - Staphylococcus aureus in community-acquired pneumonia.

PMID- 16899874
TI  - Resource allocation issues and clinical practice guidelines.

PMID- 16899875
TI  - Shift work in intensive care.

PMID- 16899877
TI  - Work shift model for housestaff in the medical ICU.

PMID- 16899899
TI  - Proceedings of the 13th Conference of the European Society for Clinical
      Hemorheology (E.S.C.H.), Siena, Italy, June 26-29, 2005.

PMID- 16899901
TI  - Fahraeus Lecture 2005: Hemorheology and vascular diseases: red cell should rub up
      to the wall, leucocytes should cope with it.

PMID- 16899902
TI  - Studies of electrorheological properties of blood.
AB  - The electrorheological (ER) properties of blood indicate changes in the blood
      rheological behaviour due to imposition of electric field. The present work
      identifies and quantifies ER properties of blood at different shear rates and at
      different local structure of the flow field. A concurrent measurement system,
      based on a Contraves Low Shear 30 rotational rheometer was used in this study. It
      includes a pair of cylindrically shaped platinum electrodes, embedded into the
      wall of a resin replica of the Couette type flow chamber of the rheometer,
      constructed for conductivity measurement, and associated software (Data
      acquisition system). The relationship between the whole blood and plasma
      conductivity (the main active component of blood impedance) was studied in
      parallel with the changes in the rheological behaviour under steady and transient
      flow conditions. The time variation of blood conductivity at different flow
      regimes and the dependences of the apparent whole blood and plasma viscosity were
      investigated in the presence and absence of an electric field of 2 kHz. The
      results show that blood conductivity is strongly dependent on the blood factors
      considered and that any application using blood conductivity measurement should
      take into account the effect of flow, shear rates and hematocrit. The results
      also show that valuable information on the mechanical properties of blood can be
      obtained, in particular concerning the structuring and kinetics of "rouleaux
      formation".

PMID- 16899903
TI  - Ischemia and reperfusion: the endothelial perspective. A radical view.
AB  - Ischemia and reperfusion (IR) injury causes a variety of changes in tissue
      homeostasis that lead to necrosis and/or programmed cell death. Due to its
      strategic location at the luminal surface of vessels, the vascular endothelium is
      particularly sensitive to IR. In particular, endothelial biosynthetic activities
      (and their protective effects) appear to be impaired by the oxidative burst
      induced by a sudden increase in oxygen free radical species upon reperfusion.
      Importantly, this endothelial damage can be easily assessed in vivo in humans by
      measuring endothelium-dependent vasorelaxation. Paradoxically, recent studies
      have emphasized the central role of free radicals (including oxygen free radicals
      and nitric oxide) also in a protective process, denominated ischemic
      preconditioning, i.e. a condition whereby a given stimulus can increase the
      tolerance of a tissue to IR damage. We discuss the role of the endothelium in
      determining the mechanism of IR injury, and on the other side, the effect of IR
      injury on endothelial function. In particular, we focus on the role of reactive
      free radicals in endothelial IR injury and in the development of ischemic
      preconditioning.

PMID- 16899904
TI  - Hemorheology and hemodynamics: Dove andare?
AB  - The rheologic characteristics of blood and its formed elements continue to be of
      basic science and clinical interest, with numerous publications dealing with
      topics such as blood and plasma viscosity, RBC aggregation and cell
      deformability. Alterations of blood's rheologic behavior in pathologic states
      have been extensively studied, with the findings usually indicating changes
      assumed to be detrimental to tissue perfusion (e.g., increased RBC aggregation).
      However, the current literature contains relatively few studies dealing with two
      important areas: (1) relations between altered rheologic behavior and in vivo
      hemodynamics; (2) the effects of therapy in those clinical states associated with
      altered rheologic behavior. This paper presents brief and selective comments on
      the assumed importance of two rheologic "abnormalities" (i.e., increased plasma
      viscosity, increased RBC aggregation), and on whether clinical therapy in
      diabetes, hypertension and sepsis leads to normalization of the "abnormalities".
      Finally, a few gratuitous comments are presented regarding possible future
      directions in the field of hemorheology and hemodynamics.

PMID- 16899906
TI  - Beneficial effects due to increasing blood and plasma viscosity.
AB  - Increased plasma and blood viscosity are usually associated with pathological
      conditions; however there are several situations in which the elevation of both
      parameters results in increased perfusion and the lowering of peripheral vascular
      resistance. In extreme hemodilution 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 Nitric oxide (NO) production via restoration of shear stress at
      the endothelium as shown by microelectrode perivascular measurements of NO
      concentration. Moderate elevations of blood viscosity by increasing hematocrit
      (approximately 10% of baseline) result in reductions of blood pressure by 10 mmHg
      of baseline. This effect is also NO mediated since it is absent after N-nitro-L
      arginine methyl ester (L-NAME) treatment and in endothelial NO synthase deficient
      mice. These results show that the rheological properties of plasma affect vessel
      diameter in the microcirculation leading to counterintuitive responses to the
      increase in viscosity.

PMID- 16899905
TI  - Hemorheological parameters as determinants of myocardial tissue hematocrit
      values.
AB  - It is well known that the hematocrit in microvessels with diameters smaller than
      1000 microm is lower than either venous or arterial hematocrit, thereby resulting
      in significantly lower mean hematocrit values for vessels perfusing a given
      tissue (i.e., lower tissue hematocrit). The mechanisms that underlie this
      reduction of microvascular hematocrit include axial migration, plasma skimming
      and the Fahraeus Effect. It has been previously demonstrated in rats that a
      linear hematocrit gradient normally exists through the thickness of the left
      ventricular myocardium, and that this gradient is sensitive to alterations of the
      rheological properties of the circulating blood. The gradient is abolished if the
      RBC in the perfusate are rigid; fibrinogen infusions, and thus increases of both
      plasma viscosity and RBC aggregation, also affect this gradient. In a new series
      of studies, it has been observed that enhanced RBC aggregation affects the
      myocardial hematocrit gradient regardless of alterations of plasma viscosity.
      Although the exact mechanisms responsible for the myocardial hematocrit gradient,
      as well as its physiological significance, are not yet clearly known, it is
      possible to speculate that alterations in local hematocrit could adversely affect
      myocardial perfusion and function.

PMID- 16899907
TI  - Local and systemic hemorheological effects of cerebral hyper- and hypoperfusion
      in a porcine model.
AB  - Using a well defined pig model, we investigated whether cerebral hypertension and
      hypotension influence hemorheological factors. After surgical preparation and
      stabilization, periods of hyperventilation, controlled periods of cerebral
      perfusion pressure increases and decreases were utilized. After each period,
      blood samples were collected from the cannulated femoral artery and vein, and
      from the superior sagittal sinus. Erythrocyte deformability, whole blood and
      plasma viscosity and hematological parameters were determined. Erythrocyte
      deformability significantly worsened in arterial samples after hypertension and
      hypotension, and in sinus samples it was impaired after hypotension period.
      Hematocrit significantly increased in arterial and sinus samples during
      hypertensive period, accompanied by similar alterations in whole blood viscosity.
      We conclude that hemodynamic changes caused by hyperventilation, hyper- or
      hypotension can influence hemorheological factors, and suggest that the
      rheological alterations can affect local hemodynamic and metabolic conditions.

PMID- 16899908
TI  - Viscosity, hemostasis and inflammation in atherosclerotic heart diseases.
AB  - BACKGROUND: In atherosclerotic diseases vascular reserve is impaired and pressure
      gradient is decreased, therefore the reduced blood fluidity can lead to tissue
      ischemia more rapidly. In previous investigations we demonstrated the
      deterioration of plasma and whole blood viscosities in patients with acute
      ischemic coronary syndromes, chronic coronary artery disease, and percutaneous
      transluminal coronary angioplasty. METHODS: Hemorheological variables (plasma and
      whole blood viscosities, hematocrit, red blood cell aggregation),
      hemostaseological parameters (plasma fibrinogen and von Willebrand factor (vWf)),
      and platelet aggregation were detected in more recent studies in cardio- and
      cerebrovascular diseases, and diabetes mellitus. Common risk factors (lipid
      profile, smoking, glucose level, previous diseases) and medication were also
      recorded. RESULTS: High portion of vascular patients were demonstrated to have
      poor ex vivo platelet inhibition. Effective antiplatelet treatment detected by
      aggregometry was related to lower plasma fibrinogen concentration and red blood
      cell aggregation and was also associated with less recurrent vascular events
      during the follow-up (p < 0.001). Beside the impaired hemorheological
      characteristics, the diabetic patients showed elevated vWf activity, which turned
      to correlate with hemoglobin A1c concentration (p < 0.01) rather than the fasting
      glucose. SUMMARY: Our studies indicate the active role and interaction of
      hemorheological and hemostaseological factors in atherosclerotic heart diseases.

PMID- 16899909
TI  - Contribution of the -455G/A polymorphism at beta-fibrinogen gene and of the
      Leiden mutation to hemorheological parameters in ischemic stroke patients.
AB  - The concentration of plasma fibrinogen (FIB) is an important factor in the
      coagulation cascade and also in the determination of blood and plasma viscosity
      depending on both genetic and acquired factors. The -455G/A polymorphism of the
      beta-FIB gene is connected to the plasma concentration of FIB but the effect of
      Leiden mutation on hemorheological parameters is unclear. The two genetic
      polymorphisms were studied by polymerase chain reaction in healthy subjects and
      ischemic stroke cohort and the effects on the concentration of plasma FIB, whole
      blood and plasma viscosity of patients as well. A total of 278 ischemic stroke
      patients and 173 control subjects were enrolled. Marcro-rheological parameters as
      plasma FIB concentration, whole blood viscosity (90 sec(-1) shear rate) and
      plasma viscosity have been measured also in the subgroup of young (age < 50
      years) and in a subgroup of non-smoker patients. RESULTS: No significant
      difference was found in the prevalency of H1/H2 genotype between controls and
      cases in pooled stroke group OR 0.95 (95% CI: 0.47-1.27), however H2/H2 genotype
      frequency was increased in young subgroup of patients (OR: 1.66 95% CI: 0.52
      5.25). Plasma FIB concentration was increased both in the total cohort (p < 0.05)
      and in the non-smoker subgroup (p < 0.03) of patients carried H2/H2 as compared
      to H1/H1 genotype and the prevalence was increased in the group of patients
      having plasma FIB concentration > 4 g/l (p < 0.05). The whole blood viscosity was
      elevated in the H2/H2 group as compared to the group carrying wild type (p <
      0.03). A tendency of increased plasma viscosity in the group of patients with
      H2/H2 genotype as compared to wild type was found (p = 0.07). Leiden mutation
      prevalence showed an increased risk OR: 1.67 (95% CI: 0.75-3.70) in the young
      patients group as compared to controls. In patients who have had the highest
      plasma viscosity, higher frequency of Leiden mutation was detected as compared to
      wild type, in total group (p = 0.01), in young patients (p = 0.03) and in
      subgroup of non-smoker patients (p = 0.05). CONCLUSIONS: Our findings support the
      notion that the homozigous variant of beta-FIB gene can raise both plasma FIB
      concentration and whole blood viscosity. Leiden mutation connected to the
      elevation of plasma viscosity could demonstrate a new pathway of increased
      thrombophylic potential in ischemic stroke patients.

PMID- 16899910
TI  - Study on the hemorheological parameters of oldest-old residents in the East
      Hungarian city, Debrecen.
AB  - The aim of this study was to assess social and health status of residents older
      than 90 years in an East-Hungarian city. The investigation involved 70 subjects,
      measuring routine laboratory parameters and plasma viscosity. Mean cholesterol,
      erythrocyte sedimentation rate (ESR), collagen cross links and plasma viscosity
      values exceeded the reference range, but mean red blood cell count, hematocrit
      and hemoglobin were below it. Plasma viscosity was found pathologically elevated
      in 51% of cases. We compared these results with an earlier laboratory screening
      test performed on the same population with the age range of 60 to 90 years. In
      this cohort the mean fibrinogen concentration, ESR, HDL-cholesterol and collagen
      cross links values were higher, but mean cholesterol, triglyceride, total
      protein, hemoglobin and hematocrit values were lower than the reference range.

PMID- 16899911
TI  - Hemorheological parameters and aging.
AB  - BACKGROUND: There is increasing evidence that impaired hemorheological parameters
      are associated with increased risk of cardio- and cerebrovascular events. The aim
      of our present study was to examine the relationship of these parameters to the
      advancing age. METHODS: The data of 6236 cardio- and cerebrovascular patients
      (3774 males, mean age 59.8 +/- 13.2 years and 2462 females, mean age 60.9 +/-
      12.8 years) were included into this analysis. Males and females were divided into
      three groups, A < 45 years of age (young), B 45-65 years (middle-aged), C > 65
      years (old). To exclude the effect of risk profile, previous diseases and
      medication, 623 patients (397 males, mean age 60.2 +/- 12.7 yrs and 226 females,
      mean age 60.5 +/- 12.4 yrs) were selected from the examined group with matching
      parameters. Blood was collected after an overnight fasting. Hematocrit,
      fibrinogen, red blood cell aggregation, plasma and whole blood viscosity were
      determined. RESULTS: All the measured parameters correlated significantly with
      advancing age in the whole population (p < 0.01), however the values of the
      correlation coefficients were very low. On the other hand, examining the
      different age-groups we found that these parameters did not consequently
      correlate with age, in fact hematocrit, red blood cell aggregation and whole
      blood viscosity values were negatively correlated with age in old males (p <
      0.05). In the selected population these parameters did not correlate with
      advancing age. CONCLUSIONS: In the whole population the correlation of
      hemorheological parameters and advancing age may be just of statistical, but not
      clinical significance because of the high number of subjects. In the selected
      population these parameters did not correlate with advancing age. Our results
      suggest that these parameters are mostly independent of aging, increased values
      are not associated with older age but the more frequently occurring diseases.

PMID- 16899913
TI  - Influence of extra corporeal circulation on myocardial oxygen tension: results of
      an animal model.
AB  - BACKGROUND: Experimental data have shown the potential risk of cellular damage of
      the myocardium during extra corporeal circulation (ECC). The influence of ECC on
      myocardial oxygen tension however remained unclear. Therefore, the influence of
      ECC on the oxygen tension in a beating heart was investigated. METHODS: In a pig
      animal model flexible pO2 microcatheters were positioned in the midmyocardium of
      the left ventricle and the skeletal muscle and tissue oxygen tension during ECC
      were monitored and compared with data of a control group without ECC. RESULTS:
      ECC and unload of the heart caused a significantly higher increase of myocardial
      pO2 than in a non-ECC control group. CONCLUSION: Our findings show the beneficial
      effect of ECC on myocardial pO2. This may support the use of ECC in coronary
      artery bypass grafting because the potential myocardial injury due to ECC is not
      related to myocardial ischemia. On the contrary, myocardial pO2 was even
      increased during extracorporeal circulation in this study.

PMID- 16899912
TI  - Gender differences in hemorheological parameters of coronary artery disease
      patients.
AB  - Plasma fibrinogen concentration, plasma and whole blood viscosity (WBV) are
      independent risk factors of coronary artery disease (CAD). Fibrinogen seems to be
      a relatively stronger risk factor for women than for men, but men are more
      endangered by higher hematocrit (Hct) and WBV than women are. We have previously
      reported that a theoretically optimal Hct value can be determined using Hct/WBV
      ratio in healthy subjects, hyperlipidemic and Raynaud's disease patients. Our aim
      was to examine whether Hct/WBV ratio is differently correlated with Hct in men
      and women with proven CAD. In a retrospective study we analysed the
      hemorheological data of 162 CAD outpatients (107 men and 55 women). Coronary
      angiography, echocardiography and impedance cardiography were performed.
      Hemorheological parameters (Hct, fibrinogen level, plasma viscosity, WBV), blood
      picture, serum lipid concentrations were determined and Hct/WBV ratio was
      calculated. Mean ages of male and female patients were similar (54.9 and 55.4
      years, respectively), but men had significantly higher coronary angiography score
      than women. Mean left ventricular ejection fraction, stroke volume index and
      cardiac index showed no significant differences in men and women. Similarly,
      lipid concentrations, fibrinogen levels and plasma viscosities demonstrated no
      statistical differences. However, Hct, WBV and Hct/WBV ratios were significantly
      higher in male than in female patients (p < 0.00001; p < 0.00001 and p < 0.005,
      respectively). The most striking gender difference was found in the correlation
      between Hct/WBV ratio and cardiac index. Men older than 56 years showed negative,
      women positive correlation (r = -0.485, p = 0.01; r = 0.468, p = 0.006,
      respectively). This study demonstrates that Hct/WBV ratio as a rheological oxygen
      carrying capacity parameter is positively correlated with the cardiac index as it
      can be expected. However, the correlation is negative in elder men indicating an
      unhealthy relation between hemodynamic and hemorheologic parameters.

PMID- 16899914
TI  - The hemorheological aspects of the metabolic syndrome are a combination of
      separate effects of insulin resistance, hyperinsulinemia and adiposity.
AB  - The metabolic syndrome which is at high risk for diabetes and atherothrombosis is
      associated with hemorheologic abnormalities. Initially, insulin resistance was
      considered as the core of the syndrome. However, it becomes clear that the
      syndrome is a cluster in which the combined effects of obesity, insulin
      resistance, and hyperinsulinemia can be inconstantly associated, contributing to
      a various extent to a global impairment of blood rheology. We previously reported
      in 157 nondiabetic subjects that both obesity and insulin resistance increase red
      cell rigidity (Dintenfass's Tk) and plasma viscosity (eta p), and that whole
      blood viscosity at high shear rate (eta b 1000 s(-1)) reflects rather obesity
      than insulin resistance. In this study we aimed at defining the specific
      hemorheologic profile of insulin resistance and hyperinsulinemia by separating a
      sample of 81 subjects into 4 subgroups according to quartiles of insulin
      sensitivity (SI) (measured with the minimal model of an intravenous glucose
      tolerance test) and baseline insulin. Results show that (1) values of SI within
      the upper quartile are associated with low eta b due to low eta p; (2) low SI
      regardless insulinemia is associated with increased aggregation indexes; (3) when
      low SI is associated with hyperinsulinemia (insulin the upper quartile and SI in
      the lower) there is a further increase in eta b due to an increase in eta p; (4)
      neither SI nor insulinemia modify Hct. Thus hyperinsulinemia and insulin
      resistance induce hyperviscosity syndromes which are somewhat different, although
      they are associated most of the time. Low SI increases RBC aggregation while
      hyperinsulinemia increases eta p.

PMID- 16899915
TI  - Rheometrical and computational studies of blood viscoelasticity during
      coagulation.
AB  - The rheological behaviour of coagulating human blood has been measured using
      multiple strain wave frequencies. The results indicate that coagulating blood,
      prior to the point of incipient clot formation, can be modelled by a modified
      form of the Gross-Marvin 'ladder' model, and the benefits of such modeling for
      blood coagulation are discussed.

PMID- 16899916
TI  - Whole blood viscosity and erythrocyte hematometric indices in chronic heroin
      addicts.
AB  - Whole blood viscosity (WBV) and hematometric indices of erythrocytes as red blood
      cell count (RBC), mean erythrocyte volume (MCV), hemoglobin (HGB), hematocrit
      (HCT), mean hemoglobin content of erythrocytes (MCH), HGB/HCT values (MCHC) and
      red blood cell distribution width (RDW) have been studied in a group of 15
      chronic opioid addicts under methadone maintenance therapy with mean age 26.53 +/
      7.34 years. WBV elevation and changes in MCV, HGB, HCT, RDW were found in
      intravenous drug users compared to healthy individuals. As well, RBC was
      decreased leading to an increase in MCH and MCHC values. Correlation analysis
      suggested that the correlation among the RBC, HGB, HCT and WBV was the closest.
      Heroin macrocytosis (heroin macrocytic anemia) was established, related with the
      increased RDW in chronic heroin abusers. The results are in accordance with data
      revealing abnormal effects of alcohol and other drugs on whole blood rheology and
      hematometric/morphometric characteristics of erythrocytes.

PMID- 16899917
TI  - Rheological properties of blood and parameters of platelets aggregation in
      arterial hypertension.
AB  - The results of some researches specify the important role of blood rheological
      properties changes in arterial hypertension (AH) pathogenesis. The goal of our
      study is to investigate the parameters of hemorheology and platelet aggregation
      in patients with various grade of AH. The study was carried out on 27 patients
      with grade 1 AH (group 1), 24 patients with grade 2 AH (group 2) and 29 healthy
      subjects (group 3). In patients of these groups, we evaluated erythrocytes
      deformability, red blood cells and platelets aggregation, blood and plasma
      viscosity. Using intra-vital computer-associated microscopic system we
      investigated microcirculation of bulbar conjunctiva. We observed that the rate of
      ADP-induced platelets aggregation is higher in group 1 as compared to groups 2
      and 3. In groups 1 and 3, red blood cells rigidity index is significantly lower
      as compared to group 2. Erythrocyte aggregability is higher in group 2 in
      comparison with groups 1 and 3. The results obtained demonstrate that mild
      hypertension is associated with the rise of platelets aggregability, moderate
      hypertension is accompanied by the reduction of red blood cells deformability and
      increase of erythrocyte aggregability. These data may reflect differences in
      conditions for the formation of microcirculation disorders in AH of various
      grade.

PMID- 16899918
TI  - Effects of nattokinase, a pro-fibrinolytic enzyme, on red blood cell aggregation
      and whole blood viscosity.
AB  - The vegetable cheese-like food, natto, is extremely popular in Japan with a
      history extending back over 1000 years. A fibrinolytic enzyme, termed
      nattokinase, can be extracted from natto; the enzyme is a subtilisin-like serine
      protease composed of 275 amino acid residues and has a molecular weight of 27.7
      kDa. In vitro and in vivo studies have consistently demonstrated the potent pro
      fibrinolytic effect of the enzyme. However, no studies to date have evaluated the
      effects of nattokinase on various hemorheological parameters and thus we have
      begun to assess the effects of the enzyme on RBC aggregation and blood viscosity.
      Blood samples were incubated with nattokinase (final activities of 0, 15.6, 31.3,
      62.5 and 125 units/ml) for 30 minutes at 37 degrees C. RBC aggregation was
      measured using a Myrenne MA-1 aggregometer and blood viscosity assessed over 1
      1000 s(-1) with a computer controlled scanning capillary rheometer (Rheolog). Our
      in vitro results showed a significant, dose-dependent decrease of RBC aggregation
      and low-shear viscosity, with these beneficial effects evident at concentrations
      similar to those achieved in previous in vivo animal trials. Our preliminary data
      thus indicate positive in vitro hemorheological effects of nattokinase, and
      suggest its potential value as a therapeutic agent and the need for additional
      studies and clinical trials.

PMID- 16899919
TI  - The importance of circadan rhythm alterations in erythrocyte deformability.
AB  - The hormone melatonin, secreted from the pineal gland at night and suppressed
      during the day, provides a circadian and seasonal signal to the organism. The
      impact of pharmacological doses of melatonin on erythrocyte deformability was
      investigated by our group in several studies in both in vitro and in vivo
      conditions. The aim of this study was to investigate the effects of alterations
      in the physiological melatonin levels via the circadian rhythm on erythrocyte
      deformability. 50 male rats weighing 250-300 g were divided in 5 groups. The rats
      were subjected to 12/12, 24/0, 0/24, 16/8 and 8/16 h of Light/Dark (L/D) cycle,
      respectively. The elongation indexes (EI) of the erythrocytes were measured by a
      laser diffractometer (Myrenne Rheodyne SSD) by using 30 microl of whole blood
      suspended in 2 ml of Dextran 60. There was no significant difference in the EI of
      the 24/0 h L/D group compared to the control (12/12), whereas the decrease of EI
      was statistically important in the 0/24 h L/D group (p = 0.009). This decrease in
      EI was also significant when this group was compared to the 24/0 h L/D group (p =
      0.05). Furthermore, the EI was affected significantly by alterations in the
      circadian rhythm, compared to control (16/8, 8/16 h L/D; p = 0.05 and p = 0.007,
      respectively). As a result, the alterations in physiological melatonin levels via
      different circadian rhythms have significant impacts on the deformability of
      erythrocytes, which therefore may cause important cardiovascular implications in
      the people who are exposed to different light dark cycles. Furthermore, these
      data represents a new and a quite crucial open-field to be investigated and taken
      into account in in vivo hemorheological studies.

PMID- 16899920
TI  - Red blood cell (RBC) surface acetylcholinesterase showing a hemorheological
      pattern during glaucoma treatment.
AB  - BACKGROUND: Glaucoma is currently attributed to two different possible
      pathogenetic mechanisms: mechanical (the ocular damage is induced by physical
      injury), and vascular (the ocular damage is sustained by ischemia of the optic
      nerve head). AIM: We considered the possibility that several anti-glaucoma drugs
      (beta-blockers, carbonic anhydrase inhibitors and prostaglandins) could have an
      influence on optic nerve head hemorheology and oxygen supply. MATERIALS AND
      METHOD: We studied 4 groups of 10 subjects each: a control group, and 3 primary
      open angle glaucoma (POAG) groups, treated with topical beta-blockers, (10
      patients), carbonic anhydrase inhibitors (CAI), and prostaglandin analogs (PG),
      respectively. In these 4 groups we investigated the RBC surface AchE and
      cytosolic calcium levels in order to assess their possible influence on the
      hemorheology and microcirculation in optic nerve head blood perfusion. RESULTS: A
      significant correlation (p < 0.048) was found between the RBC surface
      acetylcholinesterase and RBC intracytosolic calcium values in patients with POAG
      treated with beta-blockers. We found no significant correlation (p = n.s.)
      between the same patterns in the other Groups or in Controls. CONCLUSION: These
      data indicate that CAI and PG drugs do not interfere with AchE in POAG patients,
      whereas beta-blockers negatively affect the RBC deformability.

PMID- 16899921
TI  - Plasma lipids and blood viscosity in patients with cerebrovascular disease.
AB  - It is known that plasma lipids could increase the cerebrovascular risk through
      alteration of the hemorheological profile. The aim of the study was to evaluate
      the relationship between blood viscosity parameters and plasma lipids in patients
      with cerebrovascular disease (CVD). The study included 43 patients with transient
      ischemic attacks (TIAs), 53 patients with chronic unilateral cerebral infarctions
      (UCI) and 57 patients with risk factors (RF) for CVD. Whole blood viscosity (WBV)
      at different shear rates by Couette rotational viscometer Contraves Low Shear 30,
      plasma viscosity (PV) with capillary viscometer, hematocrit (Hct), fibrinogen
      (Fib), Cholesterol (Chol), triglycerides (Tg) and high-density lipoproteins (HDL)
      were examined in all patients and in a control group of 56 presumed healthy
      subjects. The hemorheological results showed increase of Hct, Fib, WBV and PV in
      the patients with TIAs and UCI; it was more pronounced in the UCI patients.
      Significant increase of Hct and WBV in the group with RF for CVD was also found.
      The elevation of Chol and Tg predominated in the patients with UCI and in the
      subjects with RF for CVD. These lipid variables correlated significantly with PV
      in the TIAs and RF for CVD groups. Conclusion is drawn about the significance of
      plasma Tg for decrease of blood fluidity and for impairment of the cerebral
      circulation in CVD.

PMID- 16899922
TI  - Responses of platelet activation and function to a single bout of resistance
      exercise and recovery.
AB  - The present study was designed to investigate the effects of resistance exercise
      and recovery on platelet activation and function. Twenty one healthy male
      subjects (27.9 +/- 4.8 years) completed three sets of five to seven repetitions
      of six exercises at an intensity corresponding to 80% of one repetition maximum
      (1RM), which was followed by 30 minutes recovery. Venous blood samples (20 ml)
      were obtained before, immediately after exercise and at the end of recovery and
      were analysed for platelet indices, platelet aggregation using collagen and
      various final concentrations of adenosine-5'-diphosphate (ADP), and beta
      thromboglobulin (B-TG). Resistance exercise was followed by a significant
      increase in corrected platelet count, corrected plateletcrit, and B-TG. These
      increases were transient and decreased to pre-exercise level at the end of
      recovery. When plasma samples were not corrected for changes in platelet count,
      exercise was followed by a significant increase (P < 0.05) in platelet
      aggregation using high concentration of ADP. With corrected samples, platelet
      aggregation and B-TG were not altered after exercise and recovery. It was
      concluded that heavy resistance exercise induces in vivo activation of platelets
      as manifested by an increase in platelet aggregation and a rise in B-TG and that
      these changes could be explained partially by changes in plasma volume and
      platelet count induced by exercise.

PMID- 16899924
TI  - Erythrocyte deformability and white blood cell count are associated with aspirin
      resistance in high-risk vascular patients.
AB  - Recently the phenomenon of aspirin resistance has been object of several studies,
      but no data are available on the possible role of the haemorheologic parameters
      in affecting platelet function and resistance to antiplatelet agents. Aim of our
      study was to evaluate platelet function and haemorheology in patients with acute
      coronary syndromes (ACS), receiving double antiplatelet therapy with aspirin and
      clopidogrel. The study population included 301 (231M/70F; age: 66 +/- 13 yrs)
      consecutive adult patients admitted to the Coronary Care Unit of the Azienda
      Ospedaliero-Universitaria Careggi, with diagnosis of acute myocardial infarction
      or unstable angina. We assessed: whole blood viscosity (WBV) at shear rates of
      0.512 s(-1) and 94.5 s(-1), plasma viscosity (PLV) at 94.5 s(-1) shear rate,
      erythrocyte deformability index (DI) and PFA-100 closure times with ADP (PFA/ADP)
      and epinephrine (PFA/EPI). We considered any PFA-100-EPI result < 203 sec (95th
      percentile of control distribution) to be indicative of aspirin resistance.
      104/301 patients (34.5%) had PFA/EPI CTs in the reference range (group 1) whereas
      the remaining had values higher than 203 sec (group 2). WBV at 94.5 sec (-1) s.r.
      was similar in group 1 and 2 (WBV: 4.43 +/- 0.25 vs 4.45 +/- 0.61 mPa.sec,
      respectively). PLV and WBV at 0.512 sec (-1) s.r. were slightly higher, but not
      significantly, in group 1 than in group 2 (PLV: 1.47+/-0.13 vs 1.44 +/- 0.15
      mPa.sec; p = 0.08 and WBV: 23.37 +/- 4.6 vs 22.54 +/- 3.90 mPa.sec; p = 0.07). DI
      was significantly lower in group 1 with respect to group 2 (4.05 +/- 2.93 vs 5.71
      +/- 3.30, p < 0.0001). White blood count (WBC) was significantly higher in group
      1 than in group 2 (11464 +/- 3504 vs 7867 +/- 2162, p < 0.0001). In conclusion,
      these results demonstrate that in patients with acute coronary syndromes the
      antiaggregant effect of aspirin is modulated not only by the direct action on
      platelets, but also by erythrocyte deformability and white blood cell count.

PMID- 16899923
TI  - The effect of ischemia and reperfusion on microvascular function: a human in vivo
      comparative study with conduit arteries.
AB  - Although microvascular dysfunction is of critical importance in the
      pathophysiology of myocardial ischemic syndromes, no study has investigated
      whether there are differences in the sensitivity to ischemia and reperfusion
      injury between microvessels and conduit arteries. Ten healthy young nonsmoking
      male volunteers (age range 24-45) were enrolled. Parameters measured included
      radial (conduit) artery (endothelium-dependent) flow-mediated dilation,
      microvascular cutaneous reactive hyperemia (using laser Doppler) and
      acetylcholine-induced microvascular vasodilation (laser Doppler iontophoresis).
      Data were acquired before and after ischemic injury (15 minutes of ischemia of
      the brachial artery followed by 15 minutes reperfusion) and analyzed in a
      randomized, blinded fashion. Conduit artery FMD was significantly blunted after
      ischemia (before: 7.5 +/- 1.1%; after: 2.9 +/- 1.0%, P < 0.05). Conversely,
      ischemia had no effect on microvascular reactive hyperemia (P = ns) and
      acetylcholine-induced vasodilation (P = ns). Using a human in vivo model, we
      demonstrate that microvessels are more resistant to ischemic injury as compared
      to conduit arteries.

PMID- 16899925
TI  - Capillary blood viscosity in microcirculation.
AB  - As known, at the arteriolar level there is the highest resistance to the flow due
      to the section and to the velocity with an average pressure fall of 50 mmHg (from
      85 to 35 mmHg). This resistance is expressed in sec(-1) by the ratio W/2r. This
      ratio is very high with an average value of 332 sec(-1) and viscosity at this
      high shear-rate is negligible. At the capillary level the pressure fall is 11.5
      mmHg but the vascular resistance W/2r is much lower, on average 32 sec(-1). We
      can say that if a resistance of 333 sec(-1) corresponds with a pressure fall of
      50 mmHg, then a resistance of 32 sec(-1) should correspond with a pressure fall
      of 4.8 mmHg. The highest pressure fall is due to another kind of resistance which
      we can define as "Capillary Blood Viscosity" because it depends on the
      rheological and structural characteristics of the blood. Our instrument
      reproduces the structure of the capillary district in an experimental model and
      measures the General Blood Viscosity (GBV) and the Capillary Blood Viscosity
      (CBV) at the same shear-rate and in particular at the low shear-rate when in non
      Newtonian fluids the highest increase in viscosity appears. Consequently, at the
      capillary, viscosity is dominant with respect to the other geometric and physical
      resistances. Moreover, the percentage ratio between the GBV and the CBV gives a
      physical measure of erythrocyte deformability. Knowing viscosity at shear-rate
      present in the circulatory system, we can obtain the size of RBCs aggregates in
      the different circulatory districts and their characteristics expressed like
      "aggregation bond". Changes in CBV are the only possibility in clinical practice
      to improve the circulatory flow in the capillary district because it is not sure
      that changes in the arteriolar section can improve the capillary flow or rather
      open arterio-venous anastomosis. Moreover, in the systemic circulation the
      aggregate size allows us to point out the phenomenon of cell adhesion because the
      presence of several receptors involves also the other blood cells. Finally the
      size and the stability of the RBCs aggregates can modify the endothelial thrombo
      resistance.

PMID- 16899926
TI  - Hemorheological parameters in correlation with the risk factors for carotid
      atherosclerosis.
AB  - The study aimed to follow the relationship between some hemorheological variables
      and the main risk factors (RF) for carotid atherosclerosis (CA). Carotid
      atherosclerosis was evaluated by color duplex sonography of the carotid arteries
      in 18 patients with RF for CA, 31 patients with transient ischemic attacks
      (TIAs), 21 patients with chronic unilateral cerebral infarctions (UCI) and 11
      healthy subjects without RF for CA. The examined hemorheological variables were
      whole blood and plasma viscosity, hematocrit and fibrinogen. They were correlated
      with intima-media thickness (IMT) of the common carotid and the internal carotid
      arteries and with other main RF for CA: hypertension, diabetes mellitus, coronary
      heart disease, and hyperlipidemia. The hemorheological investigation showed an
      increase in blood and plasma viscosity at different shear rates and it was more
      expressed in the group with UCI. The neurosonographic investigation revealed an
      increase in the IMT and carotid artery stenoses in the patients' groups with CVD.
      These were also more frequent in the patients with UCI. Different correlations
      were established between the hemorheological parameters, the IMT of the carotid
      arteries and other RF for CA. In the group with UCI, the hematocrit and the whole
      blood viscosity correlated significantly with the IMT, arterial blood pressure
      and cholesterol values. These data confirm the influence of the hemorheological
      parameters on carotid blood vessel walls and on blood flow in patients with CVD.

PMID- 16899927
TI  - Polymorphonuclear leukocyte membrane fluidity and cytosolic Ca2+ concentration in
      subjects with vascular atherosclerotic disease subdivided according to its
      extent.
AB  - An abnormal activation state of polymorphonuclear leukocytes (PMN) plays a key
      role in organ injury induced by vascular atherosclerotic disease (VAD) and
      diabetes mellitus (DM). PMN membrane fluidity and cytosolic Ca2+ content can be
      considered markers of PMN activation. In this research we evaluated the PMN
      membrane fluidity and cytosolic Ca2+ content in VAD subjects with and without
      type 2 DM and examined the association between these parameters and the mono- or
      polyvascular localization. We enrolled 155 VAD subjects, including 92 non
      diabetic (group A: mean age 63.6 +/- 9.2 years) and 63 diabetic patients (group
      B: mean age 65.4 +/- 7.8 years). Among group A 63 patients had monovascular and
      29 polyvascular disease; among group B 30 patients had monovascular and 22
      polyvascular disease. In each patient we evaluated the PMN membrane fluidity
      labelling the cells with the fluorescent probe 1,4-(trimethylamino)-phenyl-4
      phenylhexatriene (TMA-DPH) and the PMN cytosolic Ca2+ content marking the cells
      with the fluorescent probe Fura 2-AM. PMN membrane fluidity did not discriminate
      normal subjects from diabetic and non-diabetic VAD subjects, while cytosolic Ca2+
      content was increased in both groups. PMN membrane fluidity did not distinguish
      normal subjects from mono- or polyvascular VAD patients with and without type 2
      DM. PMN cytosolic Ca2+ content was increased especially in monovascular VAD
      patients; both mono- and polyvascular VAD subjects with DM had a PMN cytosolic
      Ca2+ content higher than normals. Our results show the presence of an increased
      PMN cytosolic Ca2+ content in diabetic and non-diabetic VAD subjects but no
      association was observed between this increase and the mono- or polyvascular
      localization.

PMID- 16899928
TI  - Connective tissue growth factor is released from platelets under high shear
      stress and is differentially expressed in endothelium along atherosclerotic
      plaques.
AB  - Connective tissue growth factor (CTGF) is overexpressed in atherosclerotic blood
      vessels. To further investigate the role of CTGF in atherosclerosis, we examined
      whether CTGF is released from platelets by high shear stress, and whether the
      expression of CTGF along the atherosclerotic lesions depends on local hemodynamic
      conditions. Human platelets were subjected to 10 dyn/cm2 or 120 dyn/cm2 and
      analysed by Western blotting. Furthermore, longitudinal sections of 25 carotid
      plaques were immunohistochemically analysed for the endothelial expression of
      CTGF. A very low CTGF amount was secreted from platelets at low shear stress
      (11.4 +/- 3.9% of total CTGF in platelets). On the contrary, high shear stress
      caused a markedly increased CTGF release from platelets (29 +/- 13.8%, p = 0.07
      vs low shear stress, n = 4). Immunohistochemical analyses showed that the mean
      numbers of CTGF-positive endothelial cells were significantly higher up-stream as
      compared with down-stream regions of the luminal surface of atherosclerotic
      vessels (21.3 +/- 3.6 vs 13.9 +/- 2.8 down-stream, p < 0.001). Moreover, in
      plaques undergoing intimal neovascularization, newly formed vessels accumulated
      particularly in up-stream parts of the lesions. In conclusion, this study
      demonstrated that CTGF is released from platelets by high shear stress.
      Furthermore, disturbed flow along atherosclerotic vessels may induce endothelial
      CTGF expression and contribute to the progress of atherosclerotic lesions.

PMID- 16899929
TI  - Hemorheological disturbances correlate with the lipid profile but not with the
      NCEP-ATPIII score of the metabolic syndrome.
AB  - The metabolic syndrome, which is associated with an high risk for diabetes and
      atherothrombosis, is associated with hemorheologic abnormalities. These
      abnormalities seem more and more to be explained by its various symptoms than by
      insulin resistance which represents theoretically the core of the syndrome. In
      this study we aimed at defining the specific hemorheologic profile of insulin
      resistance and hyperinsulinemia by separating a sample of 90 subjects into 4
      subgroups according to the clinical score "NCEP-ATPIII" which is the best
      recognized standardized definition of the syndrome. Results show no significant
      changes of blood rheology across classes of NCEP score despite a borderline rank
      correlation between RBC aggregability "M1" and the score. Whole blood viscosity
      was mostly correlated to HDL-cholesterol (r = -0.353, p = 0.007) and
      triglycerides (r = 0.574, p = 0.0001). Plasma viscosity was correlated with total
      cholesterol (r = 0.3359, p = 0.02) and with LDL-cholesterol (r = 0.357, p =
      0.03). Red blood cell rigidity "Tk" was negatively correlated to HDL-cholesterol
      (r = -0.430, p = 0.007). Aggregability "M" was correlated to total cholesterol (r
      = 0.356, p = 0.01) and "M1" to HDL-cholesterol (r = -0.406, p = 0.006). Thus,
      despite previously described correlations with glucose disposal parameters, the
      hyperviscosity syndrome of the metabolic syndrome is not proportional to its
      clinical scoring and is strongly dependent upon the lipid profile.

PMID- 16899930
TI  - The red blood cell deformability alterations under desfluran anesthesia in rats.
AB  - General anesthesia, either with inhalation or through nonvolatile anesthetics, is
      known to affect the overall cardiovascular function as well as the
      microcirculatory hemodynamics. In this study, the effects of desfluran anesthesia
      on the red blood cell deformability of young and old rats are investigated. 33
      male rats were used in the study and the rats were divided into two groups
      according to their age (young and old) comprising of two subgroups in each. First
      group was the young control (n = 5), the second was the young group treated with
      desfluran (n = 7), the third group was the old control (n = 7) and the last group
      was the old group treated with desfluran (n = 7). %6 of desfluran was applied to
      the rats with inhalation in an adjustable cage for one hour. The elongation
      indexes of the erythrocytes were measured by a laser diffractometer (Myrenne
      Rheodyne SSD). Deformability indexes of red blood cells were significantly
      increased with desfluran in young rats (p = 0.042) whereas they were
      significantly decreased in old rats (p = 0.004) with desfluran application
      compared with their controls. When we compared the young and old control groups,
      the deformability indexes were significantly higher in old ones (p < 0.001).
      However, there was no significant difference between the old and the young
      desfluran applied groups. The volatile anesthetic agent desfluran impairs the
      deformability of erythrocytes in old rats compared to their controls, whereas it
      has the opposite effects on young ones. This may be due to the alterations in
      membrane structure with age. These results reveal that the inhalation of
      anesthetics like desfluran may cause more serious problems in the elder people
      during the surgery and may influence their hemodynamic parameters.

PMID- 16899931
TI  - Comparison of blood rheological changes in the microcirculation during
      experimental hemorrhagic and traumatic shock.
AB  - OBJECTIVE: The aim of the present study was the analysis of the specific
      hemorheological disorders during the middle stages of experimental traumatic and
      hemorrhagic shock. METHODS: The following hemorheological properties were
      investigated: Red Blood Cell (RBC) aggregability, their deformability, and
      systemic hematocrit. The RBC aggregability was assessed by using the "Georgian
      technique". The RBC deformability was determined with the nuclepore membrane
      filter method of Reid. The hematocrit was measured by blood centrifugation. The
      results obtained were treated statistically by using the "Two sample T-test".
      RESULTS: We found that in the animals with traumatic shock the erythrocyte
      aggregability index increased by mean 181%, while in the hemorrhagic group this
      index on contrary decreased by mean 68% as compared to control group; The RBC
      deformability underwent a significant decrease during both traumatic and
      hemorrhagic shock: by a mean of 52% during the first and 62% during the second
      one. The systemic hematocrit decreased by a mean of 45% during the traumatic
      shock and by a mean of 50% during the hemorrhagic shock. CONCLUSION: The data
      obtained provide evidence that the hemorheological disorders are among the most
      significant microcirculatory disturbances in the pathogenesis of both the
      traumatic and the hemorrhagic shock.

PMID- 16899932
TI  - Hemorheological disorders in the microcirculation during septic shock in rats.
AB  - OBJECTIVES: The aim of the present study was the experimental analysis of blood
      rheological disorders in the microcirculation during endotoxic shock. METHODS:
      Experiments were carried out on 30 white laboratory rats of both sexes weighing
      about 200 g. The experimental animals were divided in two groups: the control
      group and the group undergoing experimental endotoxic shock. The following
      specific hemorheological properties were investigated in all animals during the
      experiments: red blood cells (RBC) aggregability, their deformability and the
      systemic hematocrit. RESULTS: We found that all the investigated hemorheological
      parameters appreciably changed underconditions of endotoxic shock. The RBC
      aggregability index was increased by a mean of 136%. As to the RBC deformability
      index was found to be decreased by 71%, and the systemic hematocrit lowered by
      31%, as compared to the same parameters in the control group. CONCLUSION: The
      data obtained provide us with evidence that the hemorheological derangements
      associated with the development of the heavy microcirculatory disorders during
      endotoxic shock, are most significant factors.

PMID- 16899934
TI  - Impairment of plasma nitric oxide availability in senescent healthy individuals:
      apparent involvement of extracellular superoxide dismutase activity.
AB  - To verify the potential involvement of the age-dependent modifications of EC-SOD
      activity in the impairment of plasma NO availability with advancing age, 40
      healthy men divided into 4 age groups for the purpose of comparison (young: 27.4
      +/- 1.5 years; middle: 50.8 +/- 2.2, years; old: 70.0 +/- 1.8 years; very old:
      86.1 +/- 1.1 years) were enrolled in this study. Plasma samples were used for
      measurements of the stable end-product nitrite/nitrate (NOx), as an expression of
      NO availability, EC-SOD activity, thiobarbituric acid reactive substances (TBARS)
      as a marker of lipid peroxidation, low density lipoprotein (LDL) copper-mediated
      oxidation in vitro and total antioxidant capacity (TEAC). Our results indicated a
      significant age-related progressive decrease of plasma NOx content and EC-SOD
      activity and their values were positively correlated (r = 0.713, p < 0.001).
      Increased TBARS amount together with reduced lag time for in vitro oxidation of
      LDL and decreased content of TEAC were observed with advancing age. Finally, EC
      SOD values were negatively correlated with plasma TBARS values (r = -0.855, p <
      0.001). Findings of the present study suggest that the decrease of antioxidant
      defence strategies play a primary role by compromising NO availability in
      normally aged individuals, particularly through a progressive decrease of EC-SOD
      activity.

PMID- 16899933
TI  - Persistence of the altered polymorphonuclear leukocyte rheological and metabolic
      variables after 12 months in juvenile myocardial infarction.
AB  - Acute myocardial infarction (AMI) is associated with an elevated
      polymorphonuclear leukocyte (PMN) count and a PMN rheological impairment. In this
      study we evaluated two major rheological aspects (membrane fluidity and cytosolic
      Ca2+ concentration) in a group of young adults with AMI. We enrolled 41 AMI
      patients (39 men and 2 women; mean age 41.0 +/- 4.0 years), who were examined 5
      10 days after AMI (T1) and 12 months later (T2). The membrane fluidity was
      obtained labelling granulocytes with the fluorescent probe 1-[4
      (trimethylamino)phenyl]-6-phenyl-1,3,5-hexatriene (TMA-DPH) and considering the
      degree of fluorescence polarization, inversely correlated to the membrane lipid
      fluidity. The cytosolic Ca2+ content was obtained marking PMN cells with the
      fluorescent probe Fura-2AM and considering the ratio between the Fura 2-Ca2+
      complex and the unchelated Fura 2 fluorescence intensity. Both parameters were
      evaluated at baseline and after in vitro activation with 4-phorbol 12-myristate
      13-acetate (PMA) at the concentration of 4.5 muM, prolonged for 5 and 15 minutes.
      At T1 the PMN membrane fluidity and cytosolic Ca2+ content in AMI patients were
      respectively decreased and increased in comparison with control group. At T2 the
      membrane fluidity was not any more different from control subjects, but there was
      also a further increase in cytosolic Ca2+ content. In vitro, PMN activation
      caused no significant variation of these parameters in the control group, while
      in AMI patients membrane fluidity significantly decreased and cytosolic Ca2+
      content increased not only during the initial stage, but also after 12 months.
      The long-term functional alteration of PMN cells observed in young adults with
      AMI confirms the role of these cells in the inflammatory response following AMI.
      In the light of these data, the use of molecules able to modulate granulocyte
      activity, such as calcium channel blockers or pentoxifylline, should be
      reconsidered in myocardial infarction, together with the usual pharmacological
      treatment.

PMID- 16899935
TI  - Partially opposite hemorheological effects of aging and training at middle age.
AB  - Aging impairs blood rheology while various training protocols improve it. The
      purpose of this study was to delineate the respective role of aging and endurance
      training on blood rheology. Thirty-two subjects [16 middle-aged men: 8 cyclists
      (MAcy) and 8 sedentary men (MAsed) and 16 young men: 8 cyclists (Ycy) and 8
      sedentary men (Ysed)] were compared in this study. Results showed higher red
      blood cell (RBC) rigidity and aggregability (AFFIBIO), lower RBC disaggregability
      (AFFIBIO) at middle age than at 25 yr, regardless of training status. However
      there was no age-related difference in whole blood viscosity at either native or
      corrected hematocrit, plasma viscosity, hematocrit, and Myrenne aggregation
      indexes M and M1. Training was associated with a reduced hematocrit in middle age
      subjects but not in 25 yr old ones. We evidenced no effect of training on red
      cell rigidity (Dintenfass's Tk index), in whole blood viscosity at either native
      or corrected hematocrit, and plasma viscosity. Thus, regular cycling at middle
      age maintains a low hematocrit but does not prevent aging-related increase in red
      cell rigidity and aggregability. Specific effects of cycling among other sports
      may explain this specific pattern.

PMID- 16899936
TI  - Effects of low-fat milk enriched with phytosterols on plasma cholesterol
      concentrations and hemorheological parameters of Wistar rats.
AB  - Clinical and experimental studies have shown that the use of phytosterol esters
      as a food ingredient reduces the plasma concentrations of cholesterol and LDL
      cholesterol, not affecting the HDL cholesterol levels. Based on the use of
      phytosterols as a food ingredient, we have conducted a 30-day feeding study with
      Wistar rats, drinking low-fat milk containing phytosterols, in order to evaluate
      the plasma cholesterol concentrations and the hemorheological parameters.
      Throughout the study, clinical observations, body weights and food and milk
      consumption were measured and at the end of the feeding period, blood samples
      were collected for biochemical and hemorheological determinations. There were no
      clinical changes, alterations in growth, food or milk consumption. In the plasma
      cholesterol and HDL concentrations there were no significant differences, but LDL
      levels decreased about 70%. In the hemorheological parameters, significant
      changes were observed in plasma viscosity and in membrane fluidity in all
      experimental groups. The blood viscosity and the erythrocyte deformability show
      significant improvements with the ingestion of the phytosterols enriched milk.
      With these results we conclude that phytosterols maintain their cholesterol
      lowering properties when incorporated in milk and can be considered a hypolipemic
      food component.

PMID- 16899937
TI  - Phytosterols in milk as a depressor of plasma cholesterol levels: experimental
      evidence with hypercholesterolemic Portuguese subjects.
AB  - Plant sterols have been reported to decrease plasma concentrations of cholesterol
      without any side effects. To evaluate the effects on plasma cholesterol
      concentrations and the hemorheological parameters, we performed a study with
      hypercholesterolemic patients (n = 19) treated with phytosterol-enriched milk (2
      g/day). Hypercholesterolemic patients (n = 15) of matched age drinking equal type
      of milk but without phytosterols were used as control group. Concentrations of
      total cholesterol, HDL-C, LDL-C and hemorheological parameters were measured in
      the beginning, after 15 and 30 days of milk intake. After 15 days of beverage
      intake, hypercholesterolemic subjects treated with phytosterol-enriched milk
      showed a significant decrease in plasma concentrations of total cholesterol and
      LDL-C by 9.62% (p < 0.05) and 12.20% (p < 0.05), respectively. After 30 days, a
      little increase in the total cholesterol and LDL-C concentrations were observed.
      In the hypercholesterolemic control group there were nonsignificant changes
      between plasma concentrations of total cholesterol, HDL-C and LDL-C during the
      study. The evaluation of plasma viscosity and erythrocyte aggregation shows no
      changes statistically significant during the study for both groups studied. The
      results obtained during the study show a positive effect with the phytosterol
      enriched milk as plasma cholesterol-lowering as combined treatment for
      hypercholesterolemia.

PMID- 16899938
TI  - Incidence of pulmonary thromboembolism (PTE) and new guidelines for PTE
      prophylaxis in Japan.
AB  - Incidence of venous thromboembolism (VTE), which had been considered a relatively
      rare disease in Japan, has been on the increase in recent years as eating habits
      have become more similar to those of the West. We have investigated the recent
      incidence data of perioperative pulmonary thromboembolism (PTE) in Japan and have
      established guidelines for the prevention of VTE. Recommended thromboprophylaxis
      is early ambulation for low risk group, elastic stocking (ES) or intermittent
      pneumatic compression (IPC) for moderate risk group, IPC or low dose
      unfractionated heparin (LDUH) for high risk group, and LDUH + IPC or LDUH + ES
      for highest risk group. The management fee for PTE prophylaxis was established
      and covered by health insurance in April 2004. Surprisingly, the incidence of
      perioperative PTE decreased just after this guideline was issued. After
      accumulation of further evidence and application of pharmacological agents, such
      as low molecular weight heparin, we will establish the advanced guidelines in the
      future.

PMID- 16899940
TI  - Comparison of erythrocyte aggregability changes during ischemic and hemorrhagic
      stroke.
AB  - The aim of this work was to perform a comparative investigation of erythrocyte
      aggregability changes in the peripheral and cerebral circulation during ischemic
      and hemorrhagic stroke. Subjects of the present study were patients with ischemic
      brain infarcts (14 patients) and with hemorrhagic stroke (21 patients) from the
      Intensive Care Unit of the Institute of Neurology and Neurosurgery. The blood
      samples were obtained from the following blood vessels: the common carotid artery
      carrying blood to the primarily damaged brain hemisphere, both jugular veins
      carrying blood from the primarily damaged and the contralateral hemispheres, as
      well as from the cubital vein to obtain specimens of the systemically circulating
      blood. Erythrocyte aggregation was evaluated by using the "Georgian technique".
      We found that the RBC aggregation indices increased in both the regional as well
      as the systemic circulation of the hemorrhagic stroke patients as compared to
      ischemic stroke patients. The results of the present study demonstrate different
      changes of erythrocyte aggregation in ischemic and hemorrhagic stroke patients.
      Therefore, the role of blood rheological properties in their pathogenesis seems
      also to be different.

PMID- 16899939
TI  - Hemorheological disorders during ischemic brain infarcts in patients with and
      without diabetes mellitus.
AB  - The aim of the present study was the comparative analysis of the role of specific
      hemorheological derangements in the pathogenesis of ischemic brain infarcts with
      and without diabetes mellitus. Blood plasma viscosity, as well as red blood cells
      (RBC) aggregability were quantitatively investigated in all patients during the
      study. Both of the above mentioned indices of hemorheological disorders were
      significantly higher in the patients with brain infarcts and diabetes mellitus as
      compared to the control and the group of ischemic brain infarcts without
      diabetes. During the ischemic stroke, blood plasma viscosity was increased by a
      mean of 9.2 per cent in the first and by a mean of 17.6 per cent in the second
      group of patients. As to the erythrocyte aggregability index, it was changed
      considerably more - by a mean of 113.8 per cent during stroke without diabetes,
      while in the diabetic patients the RBC aggregability index was found to be
      increased by a mean of 147.3 per cent. Ischemic brain infarcts in patients with
      diabetes mellitus were associated with a significant increase of the patients'
      blood rheological disorders in all the investigated cases.

PMID- 16899941
TI  - Fractal analysis of monocytes in diabetes.
AB  - Fractal dimension of pericellular membrane of monocytes was evaluated in diabetic
      patients and in control subjects. Monocytes were collected from normal healthy
      volunteers (n = 6) and from diabetic (type 1 and type 2) patients (n = 9).
      Monocytes from healthy volunteers were also stimulated in vitro with the
      ionophore A23187 or with the oligopeptide FMLP. Monocytes, obtained by Ficoll
      Hypaque, were examined with a Philips 300 transmission electron microscope. The
      cell contour was extracted, resized to a standard dimension and converted to a
      single pixel outline. Box-counting method was then applied to determine the
      fractal dimension. Fractal dimensions of monocytes appeared statistically
      increased in diabetic patients (type 1 and type 2), compared with sex- and age
      matched controls (p < 0.01, p < 0.01). The mechanism underlying the observed
      increased complexity of pericellular membrane may be explained by the in vivo
      activation of the circulating monocyte in diabetes. In effect, fractal analysis
      of stimulated in vitro monocytes showed a significant increase of complexity of
      pericellular membrane, compared with their controls (p < 0.001). Our approach was
      able to assess and quantitatively evaluate in diabetic patients morphological
      modifications of the monocyte linked to its activation, offering new parameters
      useful to follow the effects of therapeutical procedures.

PMID- 16899943
TI  - Laser diffractometry technique: clinical applications to vascular pathologies.
AB  - Hypertension (HTA) and dyslipidemia (DLP) represent major risk factors for
      cardiovascular and cerebral-vascular ischemic disease. The mechanisms through
      which they can induce vascular damage are both metabolic and mechanical.
      Hemorheological alterations in HTA are result of changes affecting both red cell
      intrinsic structure and their interactions with the plasmatic components. Several
      hemorheological determinants (biochemical, ionic, metabolic and rheologic) could
      influence and produce an impaired erythrocyte deformability determining an
      increased flow resistance in the microcirculation. The "Erythrodeformeter" allows
      obtaining the stationary and dynamical linear parameters of erythrocyte membrane
      by laser diffractometry. Stationary and oscillatory shear-induced elongation of
      cells leads to an elliptical diffraction pattern, its geometric characteristics
      being directly related to those of deformed RBC. Erythrocyte stationary
      parameters (Deformability Index, surface viscosity and elastic modulus) were
      obtained in stationary regime. Complex viscoelastic parameters (dynamic
      elasticity, dynamic loss, viscous and elastic components of the complex
      viscosity) were obtained when operating in oscillating mode. The diffractometric
      method is sensitive to detect pathological or induced alterations on RBC
      membrane, which can affect blood flow in vivo. The rheological parameters
      obtained give important information about the erythrocyte membrane and allow to
      detect and characterize erythrocyte alterations in vascular pathologies.

PMID- 16899942
TI  - Erythrocyte stiffness in diabetes mellitus studied with atomic force microscope.
AB  - The mechanical properties of erythrocyte membrane have been studied using an
      atomic force microscope. Measurements were carried out on blood samples taken
      from 7 diabetes mellitus patients and 8 healthy individuals. For each blood
      sample a distribution of a Young's modulus was constructed. It has been found
      that both the mean value and the width of the distribution in diabetic patients
      exceed the corresponding results for healthy persons by a factor greater than 3.
      The high sensitivity of the atomic force microscopy and the ability to measure
      the full distribution of the erythrocyte membrane Young's modulus makes it a
      unique, powerful and promising tool in studies of the membrane stiffness of red
      blood cells.

PMID- 16899944
TI  - Evaluation of a torsional-vibrating technique for the hemorheological
      characterization.
AB  - Clinical measurement of blood viscosity is an important parameter in the
      diagnosis of different diseases (e.g., diabetes, hypertension, cardiovascular
      diseases). The significance of blood viscosity in the microcirculatory flow is
      also of great importance. Thus, a simple and accurate evaluation of
      hemorheological properties could be an important challenge in clinical practice.
      Nowadays, validated measurements of plasma viscosity are commonly carried out
      with rotational viscometers by means of the various geometric configurations.
      However, red blood cells deform under mechanical force and this aspect could lead
      to an artificial variation in the apparent viscosity. In this work, an evaluation
      of a new technique for the viscosity determination is focused. In particular, a
      torsional oscillation viscometer was adopted (VM10AL, CBC Europe) in the presence
      and in the absence of stirring conditions at thermostated conditions. The profile
      of the rheological behaviour as a function of time was recorded and compared with
      that obtained using a cone-plate rotational viscometer (AR300, TA Instrument).

PMID- 16899945
TI  - Effect of hydroxyurea on the deformability of the red blood cell membrane in
      patients with sickle cell anemia.
AB  - Sickle cell disease is characterized by vaso-occlusive episodes, mainly in the
      small vessels, resulting in tissue ischemia, multi-organ failure, and,
      occasionally, death. Hydroxyurea (HU) is an agent with important and effective
      role in the treatment of patients suffering from this disease. The purpose of
      this study was to estimate the effect of HU on the deformability of the red blood
      cell's membrane (RBCM) in an effort to possibly improve the rheological
      properties of the RBCs of patients with sickle cell anemia (SCA), as well as to
      investigate the mechanical and rheological properties of these cells using
      micropipette and filtration techniques. The rigidity index, IR, which is a
      measure of cell rigidity and the elastic shear modulus, mu, which is a measure of
      cell's membrane deformability (CMd), of the RBCs from normal subjects, used as
      normal controls, were found significantly lower as compared to those of patients
      with SCA, regardless the treatment with HU. Patients under treatment with HU
      exhibited values better than those of untreated patients, in both, IR as well as
      mu, although still worse than the values of normal controls.

PMID- 16899947
TI  - Different RBC aggregating properties of the Aalpha2Bbeta2gammaA2 and
      Aalpha2Bbeta2gammaAgamma' subpopulations of human fibrinogen.
AB  - Human fibrinogen (TF) has been separated into two fractions: F1 - homodimers with
      respect to the gamma chain, and F2 - heterodimers composed of gammaA and gamma'
      polypeptides. Their rouleaux-inducing properties were as follows: (1) both, at
      the same concentration of 0.8%, were less effective than TF; (2) F1 produced
      larger rouleaux even under static conditions of a hemocytometer where F2 was
      silent; (3) F2 induced the process when a suspension was gently sheared between
      microscopic slides. Since the synthetic peptide gamma'(414-427) inhibited the
      rouleau formation in a mixture with F2, the C-terminal amino acids of the gamma'
      polypeptide probably bind the molecule to the cell. The inhibition was feebly
      visible in the native ratio of F1/F2, implicating a compensatory effect of F1.

PMID- 16899946
TI  - The influence of sevoflurane anesthesia on the rat red blood cell deformability.
AB  - Alterations in blood rheology under the influence of anesthesia have been
      observed and discussed among the responsible factors for the deterioration of
      tissue and organ perfusion related to anesthetic procedures. Sevoflurane is one
      of the volatil anesthetics which is being used very common in surgery. In this
      study, the effects of sevoflurane anesthesia were investigated in different age
      groups of rats. 22 male rats were used in the study and the rats were divided
      into two groups according to their age (young and old) comprising of two
      subgroups in each. First group was the young control (n = 5), the second was the
      young group treated with sevoflurane (n = 5), the third group was the old control
      (n = 7) and the last group was the old group treated with sevoflurane (n = 5). %2
      of sevoflurane was applied to the rats with inhalation in a adjustable cage for
      one hour. The deformability indexes of the erythrocytes were measured by a laser
      diffractometer (Myrenne Rheodyne SSD). Deformability indexes of red blood cells
      were significantly decreased with sevoflurane in old rats (p = 0.028) whereas it
      had not any significant effect in young group compared with their controls. When
      we compared the young and old control groups, the deformability indexes were
      significantly higher in old ones (p < 0.001). However, there were not any
      significant difference between the old and the young sevoflurane applied groups.
      A volatil anesthetic agent sevoflurane has impaired the deformability of
      erythrocytes in old rats compared to their controls, whereas it had not any
      significant effect in young ones which may be due to the flexibility of the young
      erythrocytes leading them to tolerate to the environmental changes. These results
      reveal that the inhalation anesthetics like sevoflurane may cause more serious
      problems in the elder people and their hemodynamic parameters should be checked
      more seriously during the surgery.

PMID- 16899948
TI  - The diagnosis of transcapillary flow disturbances in the lungs of lung cancer.
AB  - We have made the diagnosis of transcapillary flow disturbances in the lungs of
      lung cancer patients with the available noninvasive method of videobiomicroscopy
      of eye conjunctiva with further morphometric processing of obtained data using
      PC. 77 patients with lung cancer have been studied. Using videobiomicroscopy we
      calculated the size of venous capillary sacculations, the square of capillary
      glomerules (Sg), the amplitude (A), the 'length' of the twisted part of a
      microvessel (Lt), the amplitude-length coefficient (Ca), the frequency-length
      coefficient (Cf), the size of venous capillaries (V), intravascular
      conglomeration of aggregated erythrocytes (conglomerate), RBC aggregation
      coefficient (Cs) and the degree of sludge. To evaluate the data obtained, a
      comparative morphologic investigation of histologic samples taken from the intact
      areas of the lung parenchyma has been carried out. We diagnosed moderate or
      determined disturbances in the capillary flow that were confirmed by microscopy.

PMID- 16899949
TI  - Hemorheological disorders in patients with type 1 or 2 diabetes mellitus and foot
      gangrene.
AB  - The aim of the present study was to evaluate blood rheological disorders, in
      particular RBC enhanced aggregation, and compare changes in these parameters in
      patients with type 1 and 2 diabetes mellitus. For evaluation of RBC aggregability
      in the present study we applied the "Georgian technique", which was developed and
      applied for several years in our laboratory. Its advantage is that it is a direct
      and quantitative method. In all the investigated patients, diabetes mellitus was
      complicated with the foot gangrenes. The patients were divided into two groups:
      (a) with type 1 and (b) with type 2 diabetes mellitus. We matched the RBC
      aggregability indices in both groups of diabetic patients and compared the
      obtained results with those in the healthy control group. We found that
      rheological disorders were considerably pronounced. The RBC aggregability index
      increased by 62 percent (p < 0.001) in type 1 and by 57 percent (p < 0.001) in
      type 2 diabetic patients as compared to the control group. However, there were
      insignificant differences of the RBC aggregability changes between the two groups
      of patients. Therefore we conclude that blood rheological disorders are similar
      in both types of diabetes mellitus. The disturbed blood fluidity related to the
      increased RBC aggregability in the microcirculation promotes, in particular, the
      development of legs gangrene in both types of diabetes mellitus.

PMID- 16899950
TI  - Erythrocytes dynamic viscoelasticity in beta-thalassaemia minor.
AB  - Beta-thalassaemia is a hereditary hemolytic disease, in which each clinic
      phenotype encompasses a heterogenic group of genetic alterations resulting in
      beta-globin chain synthesis decrease or absence in red blood cells. Studies on
      beta-thalassaemia carriers suggest the existence of decreased red cell
      deformability. The erythrocyte deformability in the blood stream is a well-known
      fact regarding blood circulation efficiency. Red blood cells may be considered to
      be viscoelastic and their behavior may be described according to complex
      viscoelastic parameters when they undergo oscillatory stresses. This dynamic
      behavior is physiologically important due to the in vivo pulsatile blood flow.
      The aim of the present work was to evaluate complex erythrocyte viscoelastic
      parameters in patients suffering from heterozygous beta-thalassaemia in
      comparison with healthy individuals. Our results reveal that even though
      thalassaemia erythrocytes show a decreased deformability in the stationary state,
      in a dynamic state, hemorheological alterations are only evident at low
      oscillatory frequencies, i.e., at lower frequencies in contrast with the normal
      heart rate (60 cycles/min = 1 Hz), producing no significant alterations at
      increased heart rate.

PMID- 16899951
TI  - Effects of water intake on the responses of haemorheological variables to
      resistance exercise.
AB  - To examine the effects of drinking an amount of water equal to weight loss on the
      responses of blood rheological variables, eleven healthy male subjects performed
      three resistance exercise trials. The aim of the first session was to determine
      the amount of weight loss following a resistance exercise trial at 80% of one
      repletion maximum (1RM). In the second and third sessions subjects performed the
      same resistance exercise protocol without and with drinking an amount of water
      equal to that recorded for body weight loss. Three venous blood samples were
      taken before exercise, immediately after exercise, and at the end of 30-min
      recovery and were analysed for haematocrit (Hct), haemoglobin (Hb), blood cells
      count and the main determinant of blood rheology. Haematocrit, plasma viscosity,
      fibrinogen, albumin, and total protein were significantly increased in response
      to resistance exercise and returned to pre-exercise level following 30-min of
      recovery. The changes in blood rheological variables in response to resistance
      exercise occurred similarly in both control and water trials with no significant
      difference being observed between trials. Plasma volume loss through sweating and
      respiratory tract during resistance exercise could have contributed to the
      decrease in plasma volume, though, this contribution was negligible. Therefore,
      it is concluded that the increases in blood rheological variables in response to
      resistance exercise are mainly due to plasma shifts from intravascular space to
      extravascular spaces rather than plasma volume loss through sweating and
      respiratory tract.

PMID- 16899952
TI  - Is plasma viscosity a predictor of overtraining in athletes?
AB  - There is a lack of consensus about the biological diagnosis of the overtraining
      syndrome (OTS). Recently, efforts have been made to standardize its clinical
      diagnosis (e.g., standardized questionnaires like that of the French consensus
      group on overtraining of the Societe Francaise de Medecine du Sport-SFMS). We
      previously reported that the early signs of overtraining (= "overreaching") in
      elite sportsmen are associated with a hemorheologic pattern (raised hematocrit
      and plasma viscosity etap) that suggests some degree of reversal of the
      "autohemodilution" which characterizes fitness, and that the feeling of heavy
      legs in overtrained athletes is related to higher etap and higher red cell
      aggregation. We thus investigated on a sample of 48 athletes (age 24 +/- 1 yr),
      referred for possible diagnosis of overtraining to what extent plasma viscosity
      is a predictor of OTS. From those 48 athletes 10 had a value of etap in the
      highest quartile (etap > 1.44 pPa.s) and 8 of them had a diagnosis of
      overreaching, while in the 38 whose etap was < 1.44 mPa.s there were 20 cases of
      overreachings. Overt cases of OTS were found in 1 subject of the highest quintile
      and two in the lowest. Thus the predictive value of etap for early stages
      (overreaching) or chronicized stages (overtraining syndrome) is as follows: (a)
      prediction of overreaching: sensitivity 28.57%; specificity 90%; positive
      predictive value 80%; negative predictive value 47.37%; (b) prediction of
      chronicized overtraining: sensitivity 2.70%; specificity 18.18%; positive
      predictive value; 10.00%; negative predictive value 5.26%. These results show
      that etap is a rather specific, although poorly sensitive predictor of
      overreaching but has no interest in the diagnosis of the overtraining syndrome
      itself.

PMID- 16899953
TI  - Hemorheologic effects of low intensity endurance training in sedentary patients
      suffering from the metabolic syndrome.
AB  - Hemorheologic effects of exercise training ("hemorheologic fitness") are very
      different according to the mode and the intensity of this training. We previously
      reported that low intensity endurance training in sedentary patients suffering
      from the metabolic syndrome sumultaneously improved blood rheology, body
      composition and lipid oxidation at exercise. We aimed at analyzing the link among
      these improvements in 24 patients submitted to a 2 months targeted training
      designed for increasing exercise lipid oxidation. Variations of whole blood
      viscosity at high shear rate (etab 1000 s(-1)) were explained here by two
      statistically independent determinants: hematocrit and red cell rigidity. etab
      decreased in 16 subjects, but increased in 8, due to a rise in hematocrit.
      Changes in RBC rigidity appeared to reflect weight loss and decrease in LDL
      cholesterol. Plasma viscosity was related to cholesterol and its training-induced
      changes are related to those of VO2 max ) but not to lipid oxidation. Red cell
      aggregability (Myrenne) reflected both the circulating lipids (Chol, HDL and LDL)
      and the ability to oxidize lipids at exercise. Factors associated to a post
      training decrease in aggregability (M1) were weight loss and more precisely
      decrease in fat mass, improvement in lipid oxidation, rise in HDL-Chol, and
      decrease in fibrinogen. On the whole the major determinant of hemorheologic
      improvement was an increase in cardiorespiratory fitness (VO2 max ), correlated
      with a decrease in plasma viscosity, rather than an improvement in lipid
      metabolism, although RBC aggregability and deformability exhibited clear
      relationships with lipid metabolism. For which reason Hct increased in 30% of the
      patients during this kind of training remains unclear.

PMID- 16899954
TI  - The relation between the erythrocyte nitric oxide and hemorheological parameters.
AB  - We stimulated human erythrocytes obtained from patients with hypercholesterolemia
      (HC; n = 42), renal transplantation (RT; n = 18) and hypertension (HT; n = 10)
      with acetylcholine (ACh 10 microM) and measured the amperometric NO production,
      comparing with the NO levels achieved on erythrocytes of healthy persons (n =
      27). We also measured the hemoglobin, hematocrit, erythrocyte aggregation,
      erythrocyte deformability, plasma viscosity and fibrinogen concentration from
      human blood samples. The erythrocytes NO levels were of 2.5 +/- 0.7 nM (P =
      0.038, HC), 2.4 +/- 1.1 nM (RT) and 2.2 +/- 0.8 nM (HT) against the 2.0 +/- 0.8
      nM for the control groups. For each group and at each shear stress value, the
      erythrocytes deformability decreases with the increase of the NO concentration
      after ACh stimulation. We observed a significant increase of the control values
      on the erythrocyte aggregation results on each patient group. Besides the lower
      erythrocyte deformability obtained on HC, RT and HT blood samples, the
      erythrocytes produced higher NO levels after ACh stimulation than the healthy
      ones. The power of erythrocyte hemorheological behaviour could be compensated by
      the NO production at the presence of acetylcholine. We can hypothesises that
      cholinergic drugs could be used as co-adjuvants of specific therapeutics
      compounds on these studied diseases.

PMID- 16899956
TI  - L-carnitine deficiency and red blood cell mechanical impairment in beta
      thalassemia major.
AB  - L-carnitine is an essential element of intermediary metabolism and also was shown
      to be effective in maintaining normal red blood cell (RBC) function. This study
      aimed at investigating plasma free L-carnitine concentrations and effectiveness
      of L-carnitine supplementation in protecting deterioration of RBC properties in
      beta-thalassemia major patients. Plasma free L-carnitine concentrations were
      determined in the blood samples obtained before their regular transfusion (about
      one month after the previous transfusion). Each patient received 100 mg/kg/day
      oral L-carnitine supplementation. RBC deformability, lipid peroxidation and
      intracellular free calcium concentrations were investigated before and after this
      treatment. Plasma free L-carnitine levels and RBC deformability before the
      treatment were found to be lower whereas lipid peroxidation and intracellular
      calcium concentration in RBC were higher compared to those of the control
      subjects before the L-carnitine treatment. After one month supplementation of L
      carnitine lipid peroxidation and intracellular calcium concentrations were found
      to be decreased and RBC deformability was improved, accompanying the
      significantly increased plasma L-carnitine concentrations. These results suggest
      that L-carnitine can be used as a supplement in beta-thalassemic patients, to
      prevent RBC deterioration.

PMID- 16899957
TI  - Anti-inflammatory effects of Aloe vera on leukocyte-endothelium interaction in
      the gastric microcirculation of Helicobacter pylori-infected rats.
AB  - This research was aimed to investigate anti-inflammatory effects of Aloe vera on
      leukocyte-endothelium in the gastric microcirculation of Helicobacter pylori (H.
      pylori)-infected rats. Thirty-six male Sprague-Dawley rats were divided into 3
      groups: control, H. pylori-infected, and A. vera-treated group (200 mg/kg b.w.,
      twice daily). H. pylori-inoculation was induced in the rats by the administration
      of H. pylori solution. Intravital fluorescence videomicroscopy was used to
      examine leukocyte adhesion in postcapillary venules on the posterior surface of
      stomach area on different periods after administration of A. vera. Serum tumor
      necrosis factor-alpha (TNF-alpha) level was measured in blood collected at the
      end of experiment by using ELISA technique. The results showed that in H. pylori
      infected group on day 8, the leukocyte adhesion was 13.40+/-1.00 cells/100 microm
      vessel length and the TNF-alpha was 76.76+/-23.18 pg/ml, which increased
      significantly (p < 0.05), compared with the control group (leukocyte
      adhesion(control) = 2.54+/-0.6 cells/100 microm vessel length and TNF
      alpha(control) = 9.92+/-2.62 pg/ml). Treatment with A. vera reduced the leukocyte
      adhesion (5.5+/-0.5 cells/100 microm vessel length), and TNF-alpha (26.31+/-6.38
      pg/ml) significantly (p < 0.05). In conclusion, H. pylori enhanced leukocyte
      endothelium interaction in the posterior stomach area markedly. This enhancement
      in leukocyte-endothelium interaction could be improved by the treatment of A.
      vera, associated with reduction in TNF-alpha level.

PMID- 16899958
TI  - In vitro effect of insulin on rats erythrocytes rheological behaviour.
AB  - Blood viscosity is an important cardiovascular risk factor that might be related
      to diabetes complications. Hyperinsulinemia has been suggested as "the most
      important candidate" to characterise diabetes as a risk factor for cardiovascular
      disease. There is no evidence of the beneficial effect of insulin on type 2
      diabetes erythrocytes in patients without cardiovascular disease, whereas the
      opposite is observed in those with cardiovascular disease. In the present study
      we analysed the in vitro effect of different doses of insulin on red blood cell
      rheological aspects in an obesity model. Previous studies carried out in beta
      strain rats had shown that this strain possess insulin blood levels higher than
      the ones observed in alpha strain (eumetabolic), as well as blood hyperviscosity
      and erythrocyte deformability decrease. Our results points out that in vitro
      insulin produced an increase in erythrocyte aggregability, although it did not
      modified either their osmotic fragility or erythrocyte deformability estimated by
      viscometry, even against decreased viscosity of treated erythrocytes submitted to
      increased shear rate.

PMID- 16899959
TI  - Elastase in young subjects with acute myocardial infarction: Evaluation at the
      initial stage and after 12 months.

PMID- 16899960
TI  - Modulation of RAGE expression influences the adhesion of red blood cells from
      diabetic patients.
AB  - Atherothrombotic complications are frequent in patients with type 2 diabetes. Red
      blood cells (RBC) from diabetic patients exhibited an increased adhesion which
      correlated to the extent of vascular complications. In the present study we have
      investigated the adhesive interactions of RBCs with endothelium, using flow-based
      assessments. RBCs and endothelial cells were unstimulated or stimulated using
      respectively adrenaline and TNFalpha. Adhesion assays were carried-out by drawing
      the RBC suspension through a glass microcapillary tube precoated by human
      umbilical vein endothelial cells. These microslides were then incorporated into a
      controlled flow system equipped with a computerized video-microscopic image
      analysis. RBCs from diabetic patients bind to endothelial cells and could
      withstand wall shear stresses above 0.1 Pa. After stimulation by TNFalpha the
      adhesion was 1.5-fold higher. Blocking experiments demonstrated that the adhesion
      was mediated by the receptor for AGE (RAGE). Adrenaline-treated RBCs showed a
      transient increase in adhesion at low shear stresses. Inflammatory mediators or
      catecholamine amplifying diabetic RBC adhesion may aggravate endothelial cell
      damages.

PMID- 16899961
TI  - Hemorheological status and redox homeostasis of phlebotomised porphyria cutanea
      tarda patients with diabetes mellitus and in moderate alcohol consumer.
AB  - Increase in porphyrin concentration is caused by the decreased activity of
      uroporphyrinogen decarboxylase in porphyria cutanea tarda (PCT). Iron overload,
      alcohol consumption and diabetes mellitus play role in the development of PCT. We
      investigated the hemorheological and redox-parameters from the blood of 34 male
      PCT patients and 10 male volunteers. The disfunctions were investigated by
      pathological amounts of iron and lipid metabolism. Routine laboratory and
      hemorheological parameters, plasma free SH-group concentration, H-donating
      ability and reducing power were measured by spectrophotometry. Free radical
      activity was determined by chemiluminometry method. The hemorheological
      parameters were significantly increased in all three groups of PCT patients
      compared to the controls. Negative correlations were observed between blood
      viscosity and antioxidant defence of PCT patients and in PCT patients with
      alcohol consumption. Plasma and erythrocyte chemiluminescent intensity was higher
      in PCT patients than in controls, which indicated the decrease of antioxidant
      defence. Hemorheological parameters were highest in patients with diabetes and in
      alcohol consumers. Iron overload increased free radical reactions in PCT
      patients, leading to pathological viscosity. Increased free radical reactions and
      high blood viscosity increase the risk of cardiovascular diseases.

PMID- 16899962
TI  - The full story of lithium. A tribute to Mogens Schou (1918-2005).

PMID- 16899963
TI  - Distinguishing between hypochondriasis and somatization disorder: a review of the
      existing literature.
AB  - A valid classification is important for further understanding of the somatoform
      disorders. The main disorders in this grouping - somatization disorder and
      hypochondriasis - have lengthy historical traditions and are defined in a
      contrasting manner. Various authors point to distinguishing demographic and
      clinical features, but there have been few direct comparisons of patients with
      these disorders. A review of the literature indicates those domains where
      differences are most likely to be found. Research assessing these may serve to
      refine and validate these key somatoform categories and/or dimensions.

PMID- 16899964
TI  - Randomised controlled trial of a collaborative care model with psychiatric
      consultation for persistent medically unexplained symptoms in general practice.
AB  - BACKGROUND: Patients with persistent medically unexplained symptoms often exhibit
      general dysfunction and psychiatric comorbidity and frequently resist psychiatric
      referral. The aim of this study was to evaluate the efficacy of a collaborative
      care model including training for general practitioners (GPs) and a psychiatric
      consultation model for patients with persistent medically unexplained symptoms in
      general practice. METHOD: Randomised controlled trial. Cluster randomisation at
      GP practices and multilevel analysis were performed. A total of 81 patients from
      36 general practices completed the study. A collaborative care model of training
      and psychiatric consultation in general practice in the presence of the GP was
      compared with training plus care as usual by the GP. Outcome assessment on the
      patients' well-being, functioning and utilisation of health care services was
      performed 6 weeks and 6 months later. RESULTS: All the patients had somatoform
      disorders (Whitely Index 7.46), and 86% had comorbid psychiatric disorders. In
      the intervention group, the severity of the main medically unexplained symptoms
      decreased by 58%. The patients' social functioning improved. The utilization of
      health care was lower than in the care as usual group. CONCLUSIONS: A
      collaborative care model combining training with psychiatric consultation in the
      general practice setting is an effective intervention in the treatment of
      persistent medically unexplained symptoms. Anxiety and depressive disorders are
      highly comorbid in this group. The findings warrant a larger study.

PMID- 16899965
TI  - Eye movement desensitization and reprocessing for posttraumatic stress disorder:
      a pilot blinded, randomized study of stimulation type.
AB  - BACKGROUND: Eye movement desensitization and reprocessing (EMDR) is becoming a
      recognized and accepted form of psychotherapy for posttraumatic stress disorder
      (PTSD). Yet, its mechanism of action remains unclear and much controversy exists
      about whether eye movements or other forms of bilateral kinesthetic stimulation
      contribute to its clinical effects beyond the exposure elements of the procedure.
      METHODS: Twenty-one patients with single-event PTSD (average Impact of Event
      Scale score: 49.5) received three consecutive sessions of EMDR with three
      different types of auditory and kinesthetic stimulation (tones and vibrations):
      intermittent alternating right-left (as commonly used with the standard EMDR
      protocol), intermittent simultaneous bilateral, and continuous bilateral.
      Therapists were blinded to the type of stimulation they delivered, and
      stimulation type assignment was randomized and counterbalanced. RESULTS: All
      three stimulation types resulted in clinically significant reductions of
      subjective units of distress (SUD). Yet, alternating stimulation resulted in
      faster reductions of SUD when only sessions starting with a new target memory
      were considered. CONCLUSIONS: There are clinically significant effects of the
      EMDR procedure that appear to be independent of the nature of the kinesthetic
      stimulation used. However, alternating stimulation may confer an additional
      benefit to the EMDR procedure that deserves attention in future studies.

PMID- 16899966
TI  - Cognitive-behavioural group intervention for climacteric syndrome.
AB  - BACKGROUND: During peri- and postmenopause there is a high prevalence of
      psychological symptoms such as emotional instability, depressive moods, anxiety,
      sleep disorders, and sexual dysfunction. Aetiologically relevant factors for
      discomfort are decline of sex hormones and psychosocial factors such as
      lifestyle, attitude towards menopause, pre-menopausal mental health and
      sociocultural factors. In contrast to the relevance of psychosocial factors,
      there are few studies on psychological interventions. The present study evaluates
      an open trial of cognitive-behavioural group intervention consisting of
      psychoeducation, group discussion and coping skills training for women suffering
      from climacteric symptoms. METHODS: Thirty women were enrolled in this first
      trial. Standardised (MRS, HADS-D, Partnership Questionnaire, McCoy Female
      Sexuality Questionnaire) and especially developed ('Attitudes Towards the
      Menopause') instruments were administered 3 times, twice before (T1 and T2) and
      once after the group intervention (T3). General linear model repeated measures
      were used to analyse changes in questionnaire measures. RESULTS: Taking the
      average of the two pre-intervention scores, significant improvements were
      observed in anxiety (p < 0.01), depression (p < 0.02), partnership relations (p <
      0.02), overall score of sexuality (p < 0.02), hot flashes (p < 0.01) and cardiac
      complaints (p < 0.01) from pre- to post-intervention. No changes were found for
      sexual satisfaction and stressfulness of menopausal symptoms. CONCLUSIONS: This
      pilot study points at a possible effectiveness of cognitive-behavioural
      interventions for the treatment of climacteric syndrome. Further studies will
      have to use randomised trials, comparing different treatments (HRT, phyto
      oestrogens, relaxation training, discussion groups) for their effectiveness.

PMID- 16899967
TI  - Alexithymia, risk factor or consequence of work-related stress?
AB  - BACKGROUND: Primary alexithymia has been proposed as a trait-like risk factor for
      various psychiatric disorders. Alternatively, secondary alexithymia has been
      conceptualized as an inadequate coping reaction to a stressful situation. This
      study investigated the level and the type of alexithymia associated with
      occupational stress. METHOD: On 2 occasions, 69 patients with work-related stress
      and 62 healthy participants completed self-report instruments to measure
      alexithymia (20-item Toronto Alexithymia Scale), burnout complaints (Maslach
      Burnout Inventory) and general distress complaints (Depression Anxiety Stress
      Scales, Checklist Individual Strength). Group differences in alexithymia were
      analyzed using ANOVAs. The type of alexithymia was investigated by (a)
      determining absolute and relative stability, (b) exploring state dependence by
      adjusting alexithymia for burnout and distress complaints and (c) associating
      recovery of complaints with change in alexithymia. RESULTS: Alexithymia was
      significantly elevated among patients. In the patient group, absolute stability
      of two alexithymia dimensions (identifying feelings, describing feelings) and
      relative stability of one alexithymia dimension (identifying feelings) was lower
      than in the healthy group. Cross-sectional group differences became small and
      nonsignificant after adjustment for distress complaints. Among patients, change
      in alexithymia was moderately associated with symptom recovery. CONCLUSION:
      Elevated alexithymia among patients with occupational stress is highly state
      dependent, which indicates the presence of secondary alexithymia.

PMID- 16899968
TI  - Alexithymia in obsessive-compulsive disorder - results from a family study.
AB  - BACKGROUND: Previous studies have suggested an association between alexithymia
      and obsessive-compulsive disorder (OCD). However, it is unclear to which extent
      alexithymic traits in OCD patients reflect familial deficits in cognitively
      processing and communicating feelings that are also present in their first-degree
      relatives. This study investigates the hypotheses of an elevated level of
      alexithymia in subjects with OCD and their first-degree relatives compared to
      controls and their first-degree relatives. METHODS: 82 cases with OCD and 169
      first-degree relatives were compared to 76 controls and 144 first-degree
      relatives from a German family study on OCD (GENOS). All subjects completed the
      20-item Toronto Alexithymia Scale (TAS-20). Direct or family informant interviews
      were carried out with the German version of the Schedule for Affective Disorders
      and Schizophrenia - lifetime version for anxiety disorders (DSM-IV). RESULTS: OCD
      was associated with significantly higher scores of alexithymia. However, first
      degree relatives of OCD cases and of controls did not differ in TAS-20 scores. In
      linear regression analyses, the TAS-20 total score showed significant
      intrafamilial associations within the families of control subjects but not within
      families of OCD cases. CONCLUSION: OCD is a severe mental disorder that is
      associated independently from other current comorbid axis I disorders with
      deficits in identifying and expressing feelings. However, alexithymia does not
      represent a familial risk factor for OCD.

PMID- 16899969
TI  - Associations between major depression, bipolar disorders, dysthymia and
      cardiovascular diseases in the general adult population.
AB  - BACKGROUND: Cardiovascular diseases (CVD) and affective disorders are both very
      prevalent in the general population. However, it is unclear on a population level
      if the prevalence of different subtypes of affective disorders like unipolar
      major depression or dysthymia is different in individuals with specific CVDs.
      METHODS: In 4,181 participants of the general population, lifetime prevalences
      for affective disorders were assessed through the Composite International
      Diagnostic Interview and cardiovascular diseases by self-report and subsequent
      physician-verified diagnosis. Multivariable logistic regression was used in the
      analysis. RESULTS: Prevalences of unipolar depression, bipolar disorder and
      dysthymia were significantly higher in participants with coronary heart disease
      or stroke compared to those without these CVDs. Dysthymia had a stronger (OR =
      2.03; 95% CI = 1.21-3.39) association with coronary heart disease than unipolar
      depression (OR = 1.58; 95% CI = 1.09-2.30) or any depression (OR = 1.92; 95% CI =
      1.37-2.70). In contrast, unipolar depression (OR = 2.27; 95% CI = 1.29-3.99)
      showed a significant OR for the relation with stroke compared to dysthymia that
      reached no statistical significance. The commonly used category 'any depression'
      revealed higher odds (OR = 2.50; 95% CI = 1.46-4.28) for the relationship with
      stroke than unipolar depression or dysthymia, but lower odds than bipolar I
      disorder (OR = 5.71, 95% CI = 1.23-26.66). CONCLUSIONS: Classification into
      diagnostic subgroups of affective disorders is important for an improved clinical
      and pathophysiological understanding of their relationship with CVDs. Dysthymia,
      in particular, plays an important role regarding the relation of affective
      disorders and CVDs. Future research on biological models may elucidate the
      pathophysiological link between subtypes of affective disorders and CVDs.

PMID- 16899970
TI  - Psychological aspects of primary aldosteronism.
AB  - BACKGROUND: Except for 3 case reports of Conn's syndrome presenting as
      depression, psychosocial factors have not been explored in primary aldosteronism.
      We investigated psychological correlates in primary aldosteronism using methods
      that were found to be sensitive and reliable in psychosomatic research. METHOD:
      Ten consecutive newly diagnosed patients with primary aldosteronism were studied:
      5 males/5 females; mean age (+/-SD) 45.5 +/- 6.6 years, age range 34-54 years; 4
      with an aldosterone-producing adenoma and 6 with idiopathic aldosteronism;
      systolic/diastolic blood pressure 189 +/- 20/111 +/- 7.7 mm Hg; upright plasma
      aldosterone 40.0 +/- 18.3 ng/dl; upright plasma renin activity (PRA) 0.2 +/- 0.1
      ng/ml/h; aldosterone/PRA ratio 229.2 +/- 191.0; serum K(+) 3.5 +/- 0.5 mmol/l.
      The Structured Clinical Interview for the Diagnostic and Statistical Manual of
      Mental Disorders (DSM-IV) for eliciting psychiatric diagnoses, and a shortened
      version of the structured interview for subclinical psychological syndromes, the
      Diagnostic Criteria for Psychosomatic Research (DCPR), were administered.
      RESULTS: Seven patients (2 with aldosterone-producing adenoma and 5 with
      idiopathic hyperaldosteronism) received both DSM-IV and DCPR diagnoses, while 3
      had neither. As to DSM-IV, generalized anxiety disorder was detected in 6 cases
      (in 1 it was associated with panic disorder and in 1 with major depression) and
      obsessive-compulsive disorder in 1. The most frequent DCPR cluster was
      demoralization (5 cases), while persistent somatization occurred in 2 cases
      (associated with demoralization in 1) and irritable mood in 1. CONCLUSIONS: The
      occurrence of anxiety disorders in patients with primary aldosteronism was much
      higher than that found in the general population and in primary care. Since an
      association between hyperaldosteronism and anxiety has also been suggested in
      previous animal studies, it seems worthwhile to gain further knowledge on
      clinical aspects by larger population studies.

PMID- 16899971
TI  - Troglitazone and 9cis,11trans,13trans-conjugated linolenic acid: comparison of
      their antiproliferative and apoptosis-inducing effects on different colon cancer
      cell lines.
AB  - BACKGROUND: We have previously reported that troglitazone, a synthetic ligand for
      peroxisome proliferator-activated receptor gamma (PPARgamma), and bitter gourd
      seed oil rich in 9cis,11trans,13trans-conjugated linolenic acid (9c,11t,13t-CLN)
      prevent colon carcinogenesis. To evaluate the chemotherapeutic effect and potency
      of these compounds on colon cancer cells, we investigated their antiproliferative
      and apoptosis-inducing effects using different human colon cancer cell lines.
      METHODS: The antiproliferative and apoptosis-inducing effects of troglitazone and
      9c,11t,13t-CLN were evaluated and compared using HT-29, DLD-1 and Caco-2 cells at
      different stages of enterocytic differentiation. RESULTS: Troglitazone and
      9c,11t,13t-CLN decreased cell viability and induced apoptosis in three colon
      cancer cell lines. The susceptibility of HT-29, which expresses PPARgamma at high
      levels, to troglitazone and 9c,11t,13t-CLN was higher than that of Caco-2 cells
      with low levels of PPARgamma. CONCLUSION: Troglitazone and 9c,11t,13t-CLN
      exhibited more effective chemotherapeutic effects on HT-29 cells than on Caco-2
      cells.

PMID- 16899972
TI  - Cytotoxicity of docetaxel (Taxotere) used as a single agent and in combination
      with radiation in human gastric, cervical and pancreatic cancer cells.
AB  - BACKGROUND: Docetaxel (Taxotere) has gained increasing attention in clinical
      applications. We investigated the cytotoxic and radiosensitizing potential of
      docetaxel at nanomolar concentrations in six cell lines derived from tumors that
      rarely respond to radiation or chemotherapy, with special consideration of
      mechanisms of resistance, including the p53 mutational status. METHODS: Cells
      derived from carcinomas of the human stomach (p53 mutant Hs746T, p53 wild type
      AGS), cervix (p53 wild type CaSki, p53 mutant HeLa) or pancreas (p53 mutant BxPC3
      and Capan-1) were treated for 24 h with docetaxel at various concentrations (0.1
      5 nM) to obtain drug doses for inhibiting clonogenicity by approximately 50%
      (IC(50)). Cells were X-irradiated without docetaxel or after 24 h of docetaxel
      treatment at IC(50). Radiation doses ranged from 0 up to 10 Gy. Mitotic index,
      multinucleation, apoptosis and necrosis after 24 h of drug exposure at 1 nM were
      quantified in representative gastric and cervical cell lines by fluorescence
      microscopy. RESULTS: Docetaxel treatment for 24 h resulted in a dose-dependent
      loss of clonogenicity, with 1.0 or 0.3 nM producing approximately 50% survival of
      gastric or cervix and pancreatic cells, respectively. After correction for the
      drug toxicity, the combination of isoeffective concentrations of docetaxel with
      graded X-ray doses resulted either in a moderate synergy or additivity. The dose
      reduction factors at the 50 and 20% survival levels were statistically greater
      than those for Hs746T or AGS cells. For CaSki, HeLa, BxPC3 or Capan-1 cells, the
      dose reduction factors were statistically not different from unity. CONCLUSION:
      Docetaxel was active against tumor cells of different origins. Combined effects
      of docetaxel and radiation were at least additive and depended on the intrinsic
      sensitivity to drug alone. There was no significant evidence of drug-induced
      mitotic arrest. Compared to drug-resistant gastric cells, exposure to the drug
      alone of drug-sensitive cervical cells resulted in more severe multinucleation.
      The p53 status did not contribute directly to the effect of drug alone or in
      combination with radiation.

PMID- 16899973
TI  - Investigation of potential antibacterial properties of methanol extracts from
      fungus Ganoderma applanatum.
AB  - In this study we searched for antibacterial compounds in methanol extracts of
      three layers (tube layer, context and cutis) of Ganoderma applanatum fruit body
      against Bacillus subtilis ATCC 6051 as a gram-positive bacterium and Escherichia
      coli ATCC 25922 and Pseudomonas syringae pv. syringae DPIC 219 as gram-negative
      bacteria. We found antibacterial properties in all three layers only against gram
      negative bacteria. The fractions were isolated and purified by thin layer
      chromatography (TLC) and high-performance liquid chromatography. After
      purification, four major compounds - A, B, C and D - were tested for
      antibacterial properties, and B and D were found to possess antibacterial
      properties. The results of TLC and spectral data, including mass spectra and (1)H
      NMR of compounds B and C, showed that they were saturated fatty acids and
      compound D was palmitic acid (hexadecanoic acid) (16:0).

PMID- 16899974
TI  - Fluconazole and itraconazole resistance of yeasts isolated from the bloodstream
      and catheters of hospitalized pediatric patients.
AB  - BACKGROUND: In critically ill children, Candida species and other yeasts appear
      as an important nosocomial pathogen. The emerging fungal pathogens are usually
      less susceptible to azole compounds, and the management of such infections could
      be problematic. METHODS: 6,065 bloodstream cultures and 627 catheters from
      intensive care units and hospitalized oncology pediatric patients were studied.
      Antifungal susceptibility testing of isolates was performed according to the
      reference broth microdilution method describedby the National Committee for
      Clinical Laboratory Standards (M27-A). RESULTS: We found a low activity of
      fluconazole (FCZ) and itraconazole (ITZ) against Candida glabrata, C. albicans,
      C. tropicalis and C. haemulonii. Resistant strains to FCZ and ITZ were detected.
      CONCLUSION: Results reveal the emergence of antifungal-resistant species and a
      change in the predominant role of C. albicans as a cause of candidemia in
      hospitalized children.

PMID- 16899975
TI  - Hepatocyte growth factor is a better indicator of therapeutic response than C
      reactive protein within the first day of treatment in pneumonia.
AB  - Acute bacterial infectious diseases are mostly treated empirically at admission
      before the culture results are available. According to the risk for serious
      complications in the case of therapeutic failure, it is important to evaluate the
      therapy results and change to a more appropriate antibiotic regime as soon as
      possible. In the present study, 40 patients with X-ray-verified community
      acquired pneumonia were examined and blood specimens were collected before and
      within 24 h of treatment. Body temperature, C-reactive protein (CRP) and
      hepatocyte growth factor (HGF) were investigated. Thirty-two patients received an
      appropriate initial antibiotic therapy regarding clinical outcome, but in 8
      patients the treatment was changed because of therapy failure. Changes of HGF
      levels after 18-24 h of treatment could predict the therapeutic results
      accurately in 38 of 40 cases (sensitivity 100%, specificity 94%, positive
      likelihood ratio 16.0). HGF was significantly better to predict therapy outcome
      than CRP (p < 0.0001).

PMID- 16899976
TI  - Evolution of basal ganglia surgery for movement disorders.
AB  - In 1942, it was thought that basal ganglia surgery would cause permanent
      unconsciousness and significant impairment of motor control. By 1947, when human
      stereotactic surgery was introduced, the first target was the globus pallidus in
      a patient with chorea. What happened during those 5 years to set the stage for
      stereotactic surgery? During the last half of the 19th century, it was first
      noted that motor disorders were often accompanied by atrophy of various parts of
      the basal ganglia, and when histopathology became part of necropsy, that
      relationship between movement disorders and the basal ganglia was strengthened.
      The impairment of fine motor control was noted in experiments that involved
      lesioning the basal ganglia, which led to the conclusion that disease of the
      basal ganglia might cause motor impairment. Finally, in 1939, Russel Meyers took
      the bold move of surgically resecting the head of the caudate nucleus at
      craniotomy in a patient with Parkinson's disease, demonstrating that Dandy was
      wrong in the view that the basal ganglia were the center of consciousness, and
      that symptoms and motor control might be improved by caudate lesions without
      motor impairment. He reported his first patient in a meeting in 1940, which was
      published in 1942, and was encouraged to investigate basal ganglia surgery
      further. Although results were encouraging, the mortality rate was prohibitive.
      Since the introduction of pallidoansotomy in 1947, basal ganglia surgery has
      become both safe and effective and has been expanded and refined.

PMID- 16899977
TI  - New radiofrequency coil integrated with a stereotactic frame for intraoperative
      MRI-controlled stereotactically guided brain surgery.
AB  - Mislocalization errors caused by MR image distortions or brain shift are one of
      the main causes of complications after stereotactically guided neurosurgical
      procedures. A special device, which could ameliorate such effects and provide
      intraoperative acquisition of MR images of sufficient diagnostic accuracy, was
      developed. It is composed of a radiofrequency receiver coil integrated with a
      modified Komai stereotactic frame and a Sugita four-pin head holder. Clinical
      testing revealed that the use of the device during stereotactically guided
      procedures under the control of low magnetic field strength (0.3 T)
      intraoperative MRI ameliorates the effects of brain shift, and permits to obtain
      informative tissue samples and to perform aggressive removal of the lesion
      without any damage of the eloquent cerebral structures. The possibility of an
      easy shift from a stereotactically guided to a routine microneurosurgical
      procedure represents an additional benefit of the developed device.

PMID- 16899978
TI  - Stereotactic imaging for radiosurgery: localization accuracy of magnetic
      resonance imaging and positron emission tomography compared with computed
      tomography.
AB  - Computed tomography (CT), magnetic resonance imaging (MRI), and positron emission
      tomography (PET) provide complementary information for treatment planning in
      stereotactic radiosurgery. We evaluated the localization accuracy of MRI and PET
      compared with CT. Two kinds of phantoms applicable to the Leksell G stereotactic
      skull frame (Elekta, Tokyo) were developed. Deviations of measured coordinates at
      target points (x = 50, 100, 150; y = 50, 100, 150) were determined on different
      axial planes (z = 30-140 for MRI and CT study and Z = 50-120 for PET and CT
      study). For MRI, the deviations were no more than 0.8 mm in each direction. For
      PET, the deviations were no more than 2.7 mm. For both imaging modalities
      studied, accuracy was at or below the imaging resolution (pixel size) and should
      be considered useful for clinical stereotactic planning purposes.

PMID- 16899979
TI  - MR spectroscopic changes in the rat hippocampus following proton radiosurgery.
AB  - PURPOSE: To identify MR spectroscopic changes in the rat hippocampus following
      proton radiosurgery. METHODS AND MATERIALS: A group of 12 rats were treated with
      Bragg peak proton beam irradiation involving the right hippocampus. Single doses
      of 30 CGE, 50 CGE, 70 CGE, 90 CGE were delivered to groups of 3 animals using
      single fraction technique. Animals were imaged using a standard 3 T GE Signa MRI
      at 4 months following treatment. An untreated animal was also studied. A 3''
      surface coil was employed to obtain T1 weighted coronal pre- and post-gadolinium
      images (TR 600 and TE 30) and dual echo T2 weighted coronal images (TR 3000, TE
      30/90). Volumetric analysis with custom software was done to evaluate areas of
      increased signal on T2 weighted images and the development of hydrocephalus was
      examined. Animals were sacrificed and specimens of the treated hippocampus were
      harvested for High Resolution Magic Angle Spinning MR Spectroscopy (HRMAS)
      followed by histopathology of the tissue samples. Peak values of choline,
      creatine, N-acetyl aspartate and lipids were evaluated and compared. RESULTS:
      Peak tissue injury occurred in the surviving 90 CGE animal by both T2 weighted
      and post-gadolinium imaging. Gadolinium enhancement was seen in decreasing
      volumes of tissue at dosage levels from 90 to 50 CGE. Hydrocephalus was seen on
      the untreated side in the 90 CGE animal likely because of mass effect, while it
      was seen in small degrees in the side of treatment in the 70 and 50 CGE animals.
      Histopathology showed changes at 90 and 70 CGE, but not at 50 or 30 CGE at this
      time point using H and E stains. HRMAS showed spectroscopic changes in the
      surviving 90 and 70 CGE animals but not in the 50 and 30 CGE animals. Statistical
      significance was not reached because of the small sample size. CONCLUSIONS:
      Following single dose proton radiosurgery of rat hippocampus, HRMAS is able to
      identify metabolic changes induced by radiation. Studies built on these
      principles may help develop non-invasive MR spectroscopic methods to distinguish
      radiation changes from tumor recurrence.

PMID- 16899980
TI  - Prognostic and therapeutic significance of carbohydrate antigen 19-9 as tumor
      marker in patients with pancreatic cancer.
AB  - In pancreatic cancer (PC) accurate determination of treatment response by imaging
      often remains difficult. Various efforts have been undertaken to investigate new
      factors which may serve as more appropriate surrogate parameters of treatment
      efficacy. This review focuses on the role of carbohydrate antigen 19-9 (CA 19-9)
      as a prognostic tumor marker in PC and summarizes its contribution to monitoring
      treatment efficacy. We undertook a Medline/PubMed literature search to identify
      relevant trials that had analyzed the prognostic impact of CA 19-9 in patients
      treated with surgery, chemoradiotherapy and chemotherapy for PC. Additionally,
      relevant abstract publications from scientific meetings were included. In
      advanced PC, pretreatment CA 19-9 levels have a prognostic impact regarding
      overall survival. Also a CA 19-9 decline under chemotherapy can provide
      prognostic information for median survival. A 20% reduction of CA 19-9 baseline
      levels within the first 8 weeks of chemotherapy appears to be sufficient to
      define a prognostic relevant subgroup of patients ('CA 19-9 responder'). It still
      remains to be defined whether the CA 19-9 response is a more reliable method for
      evaluating treatment efficacy compared to conventional imaging.

PMID- 16899981
TI  - Young age is associated with favorable characteristics but is not an independent
      prognostic factor in patients with epithelial ovarian cancer: a single
      institution experience.
AB  - BACKGROUND: Young age has been reported to be a favorable prognostic factor in
      ovarian cancer. The aim of the present study was to investigate the
      characteristics of ovarian cancer presenting in patients aged < or =40 and assess
      the prognostic significance of young age. METHODS: Data from 591 consecutive
      ovarian cancer patients, including 37 subjects (6.3%) aged < or =40, who were
      treated postoperatively with platinum-based chemotherapy in our institution were
      retrospectively reviewed. RESULTS: In our series, age < or =40 did not show an
      independent association with overall (p = 0.542) or progression-free survival (p
      = 0.334). Nonetheless, it was correlated with low tumor grade (p = 0.009) and
      small volume of residual disease after primary surgery (p = 0.020), while there
      was a nonsignificant trend for correlation with performance status 0 (p = 0.052).
      Stratified analysis showed that age < or =40 was associated with improved overall
      survival in the subgroups of serous histology and stage IIC-IV disease; however,
      multivariate analyses failed to identify age as an independent predictor of
      survival within either subgroup (p = 0.079 and p = 0.585, respectively).
      CONCLUSIONS: Age < or =40 was not an independent prognostic factor in our
      analysis. The survival advantage of young patients may be attributed to the
      association with low tumor grade, more complete surgical debulking and better
      performance status.

PMID- 16899982
TI  - Frequency of febrile neutropenia in breast cancer patients receiving epirubicin
      and docetaxel/paclitaxel with colony-stimulating growth factors: a comparison of
      filgrastim or lenograstim with pegfilgrastim.
AB  - OBJECTIVE: Recombinant granulocyte colony-stimulating factors (G-CSF) have been
      shown to be effective in reducing the risk of infections associated with
      antitumour chemotherapy. This report describes a single-centre experience of the
      efficacy of pegfilgrastim compared with filgrastim or lenograstim in reducing the
      incidence of febrile neutropenia in patients receiving combination chemotherapy
      with taxane and epirubicin in a neoadjuvant and adjuvant setting. METHODS: A
      total of 118 patients with breast cancer were treated with either epirubicin 75
      mg/m(2) and docetaxel 75 mg/m(2) or epirubicin 90 mg/m(2) and paclitaxel 200
      mg/m(2) every 3 weeks; 88 received G-CSF support with daily filgrastim or
      lenograstim and 30 with pegfilgrastim once per cycle. RESULTS: Eight patients
      (9.1%) with prophylactic filgrastim or lenograstim support developed febrile
      neutropenia, as well as 1 patient (3.3%) in the pegfilgrastim group (p = 0.445).
      Febrile neutropenia occurred in 13 (2.7%) of 476 filgrastim or lenograstim
      supported chemotherapy cycles and in 2 (1.2%) of 172 cycles with pegfilgrastim
      support (p = 0.376). The frequency of chemotherapy delays and dose reductions was
      not significantly different between the two G-CSF treatment groups. CONCLUSION:
      These data show a trend towards superiority of pegfilgrastim over filgrastim or
      lenograstim in reducing the frequency of febrile neutropenia in patients treated
      with taxane and epirubicin chemotherapy regimens for breast cancer.

PMID- 16899984
TI  - Readministration of IgE is required for repeated passive cutaneous anaphylaxis in
      mice.
AB  - BACKGROUND: Homologous passive cutaneous anaphylaxis (PCA) is an established
      technique that provides a useful tool to study local inflammation due to mast
      cell activation. Since mast cells are responsive to repeated challenge by IgE
      receptor crosslinking in vitro, we investigated the responsiveness of mice to
      repeated PCA activation. METHODS: Female BALB/c mice were sensitized with
      intradermal injection of IgE into the ear and provocated through intravenous
      injection of trinitrophenol-BSA. Repeated provocation was administered, and the
      outcome was determined by colorimetrical measurement of Evans blue dye leakage.
      RESULTS: After local IgE injection, mice could be challenged to demonstrate a PCA
      reaction at least up to 13 days after IgE sensitization. In contrast, passively
      sensitized mice did not respond to repeated antigen challenge, i.e. a second
      provocation administered between 1 and 12 days after the first PCA reaction.
      However, if these mice were intradermally resensitized with IgE at the same site
      after the first challenge, they became responsive to the repeated challenge.
      CONCLUSIONS: Mast cells become desensitized upon PCA reaction, and
      resensitization with IgE is critical for mice repeatedly stimulated by PCA
      activation.

PMID- 16899983
TI  - Gastro-intestinal exposure to latex antigens induce allergic responses in mice.
AB  - BACKGROUND: Natural rubber latex (NRL) has emerged as a major cause of
      respiratory allergy among specific exposed groups of individuals. Since latex
      allergens are dispersed in the environment it is conceivable that latex proteins
      are both inhaled and ingested. The mechanism of latex allergy and the immune
      responses following reexposure of latex allergens by the intranasal route was
      studied in a murine model of latex allergy developed by intragastric
      sensitization with NRL. METHODS: BALB/c mice were sensitized intragastrically
      ('ig'), intranasally ('in') or 'ig' followed by 'in' challenge with NRL
      allergens. The cellular and humoral immune responses, lung function and
      histological changes were determined. RESULTS: Peripheral blood eosinophilia was
      observed in the 'ig' and 'ig/in'-NRL-sensitized animals in comparison to normal
      controls (p < 0.05). The 'ig' group showed a marked increase over control mice in
      serum total IgE, NRL-specific IgG and IgG subclasses (p < 0.05). Increased levels
      of IL-4, IL-5, IL-10, and IL-13 were detected in 'ig'-NRL-sensitized mice.
      Intranasal exposure with NRL after 'ig' sensitization further enhanced the
      cytokine levels. A tendency towards enhanced stimulation was determined in 'ig'
      sensitized mice; a significant difference was shown in the 'ig/in'-group (p <
      0.05). Increased airway hyperreactivity was found in 'ig'-NRL-sensitized-mice
      (15.1 +/- 2.5 vs. 8.9 +/- 1.7 cm H2O x ml(-1) x s, p < 0.05). Mucus secretion
      from jejunal epithelium and eosinophilic infiltration into the jejunal lamina
      propria were observed in the 'ig'-NRL-sensitized-mice. CONCLUSIONS: The results
      demonstrate that intragastric NRL sensitization did not induce specific
      tolerance, and additional intranasal exposure with latex allergens resulted in
      systemic allergic manifestations in the murine model.

PMID- 16899986
TI  - B cell-activating factor is a novel diagnosis parameter for asthma.
AB  - BACKGROUND: Asthma is a life-threatening immediate-type allergic disease. B cell
      activating factor (BAFF) is a key regulator of B lymphocyte development and is
      required to generate and maintain the mature B cell pool. OBJECTIVES: To
      investigate the level of BAFF in the serum of asthma patients and the role of
      BAFF on T cells. METHODS: The BAFF level was measured by enzyme-linked
      immunosorbent assay. Peripheral blood mononuclear cells (PBMC) from asthma
      patients were analyzed by flow cytometry. T8.1 cells were used to test the role
      of BAFF on T cell-antigen-presenting cell (APC) conjugate formation. RESULTS: The
      BAFF level in patient serum was elevated relative to normal serum. Immunoglobulin
      E (IgE) concentration and the percentage of CD3+ T and CD19+ B cells vary
      according to the serum BAFF level. Patients with high BAFF and high IgE (group
      II) and those with high BAFF and low IgE (group III) show a high ratio of CD3+ T
      to CD19+ B cells, and the opposite is seen for patients with low BAFF and high
      IgE (group I) and those with low BAFF and low IgE (group IV). The addition of
      BAFF increased PBMC proliferation and T cell-APC conjugate formation. BAFF
      concentration in serum decreased after treatment with antiasthmatic drugs
      including glucocorticoids and immunosuppressants. CONCLUSION: These findings
      suggest that the serum BAFF level is high in both IgE-mediated asthma and non-IgE
      mediated asthma and extend our knowledge about the fact that BAFF may play a
      stimulatory role on the proliferation of T cells. Thus, BAFF could be a parameter
      to monitor the severity of asthma symptoms.

PMID- 16899985
TI  - Effects of alpha tocopherol and probucol supplements on allergen-induced airway
      inflammation and hyperresponsiveness in a mouse model of allergic asthma.
AB  - OBJECTIVE: We investigated the role of antioxidants in airway hyperresponsiveness
      to acetylcholine using young asthma model mice, which were sensitized and
      stimulated with ovalbumin. METHODS: The mice had been fed either a normal diet,
      an alpha-tocopherol-supplemented diet or a probucol-supplemented diet 14 days
      before the first sensitization. They were immunized with antigen at intervals of
      12 days and, starting from 10 days after the second immunization, they were
      exposed to antigen 3 times every 4th day using an ultrasonic nebulizer. Twenty
      four hours after the last antigen inhalation, airway responsiveness to
      acetylcholine was measured and bronchoalveolar lavage fluid (BALF) was collected.
      A blood and lung tissue study was also carried out. RESULTS: Twenty-four hours
      after the last antigen challenge, both IL-4 and IL-5 in the BALF of alpha
      tocopherol-supplemented mice were significantly decreased. The IL-5 level in
      probucol-supplemented mice was also decreased, but there was no difference in IL
      4 levels. The serum IgE level was decreased in probucol-supplemented mice.
      Differential cell rates of the fluid revealed a significant decrease in
      eosinophils due to antioxidant supplementation. Airway hyperresponsiveness to
      acetylcholine was also repressed in antioxidant-supplemented mice. In
      histological sections of lung tissue, inflammatory cells and mucus secretion were
      markedly reduced in antioxidant-supplemented mice. We investigated the
      antioxidant effect on our model mice by examining 8-isoprostane in BALF and lung
      tissue, and acrolein in BALF; however, our experiment gave us no evidence of the
      antioxidant properties of either alpha-tocopherol or probucol contributing to the
      reduction of airway inflammation. CONCLUSION: These findings indicate that alpha
      tocopherol and probucol suppress allergic responses in asthma model mice,
      although these two drugs cause suppression in different ways that are unrelated
      to antioxidation.

PMID- 16899987
TI  - Poor control increases the economic cost of asthma. A multicentre population
      based study.
AB  - BACKGROUND/AIMS: Up to now, few cost-of-illness (COI) studies have estimated the
      cost of adult asthma at an individual level on general population samples. We
      sought to evaluate the cost of current asthma from the societal perspective in
      young Italian adults and the determinants of cost variation. METHODS: In 2000, a
      COI study was carried out in the frame of the Italian Study on Asthma in Young
      Adults on 527 current asthmatics (20-44 years) screened out of 15,591 subjects
      from the general population in seven centres. Detailed information about direct
      medical expenditures (DMEs) and indirect costs due to asthma was collected at an
      individual level over the past 12 months. RESULTS: The mean annual cost per
      patient was EUR 741 (95% CI: 599-884). DMEs represented 42.8% of the total cost,
      whereas the remaining 57.2% was indirect costs. The largest component of DMEs was
      medication costs (47.3%; 23.0% was due to hospitalization). The mean annual cost
      per patient ranged from EUR 379 (95% CI: 216-541)for well-controlled asthmatics
      to EUR 1,341 (95% CI: 978-1,706) for poorly controlled cases that accounted for
      46.2% of the total cost. Poor control, coexisting chronic cough and phlegm, and
      low socio-economic status were significantly associated with high DMEs and
      indirect costs. CONCLUSIONS: In Italy, asthma-related costs were substantial even
      in unselected patients and were largely driven by indirect costs. Since about
      half of the total cost was due to a limited proportion of poorly controlled
      asthmatics, interventions aimed at these high-cost patients could reduce the
      economic burden of the disease.

PMID- 16899990
TI  - Actions of mibefradil, efonidipine and nifedipine block of recombinant T- and L
      type Ca channels with distinct inhibitory mechanisms.
AB  - We compared detailed efficacy of efonidipine and nifedipine, dihydropyridine
      analogues, and mibefradil using recombinant T- and L-type Ca2+ channels expressed
      separately in mammalian cells. All these Ca2+ channel antagonists blocked T-type
      Ca2+ channel currents (I(Ca(T))) with distinct blocking manners: I(Ca(T)) was
      blocked mainly by a tonic manner by nifedipine, by a use-dependent manner by
      mibefradil, and by a combination of both manners by efonidipine. IC50s of these
      Ca2+ channel antagonists to I(Ca(T)) and L-type Ca2+ channel current (I(Ca(L)))
      were 1.2 micromol/l and 0.14 nmol/l for nifedipine; 0.87 and 1.4 micromol/l for
      mibefradil, and 0.35 micromol/l and 1.8 nmol/l for efonidipine, respectively.
      Efonidipine, a dihydropyridine analogue, showed high affinity to T-type Ca2+
      channel.

PMID- 16899991
TI  - Effect of sodium/hydrogen exchange inhibition on myocardial infarct size after
      coronary artery thrombosis and thrombolysis.
AB  - This study examines the cardioprotective effects of Na+/H+ exchange inhibition
      with BIIB-722 or ischemic preconditioning after occlusive thrombus formation and
      subsequent thrombolysis for reperfusion. Coronary artery thrombosis was induced
      by vessel wall electrolytic injury. Thrombotic occlusion was maintained for 60 or
      90 min in 4 different groups: (1) control; (2) Na+/H+ exchange inhibitor, BIIB
      722 (3 mg/kg) before occlusion; (3) BIIB-722 (0.75 mg/kg) before reperfusion; (4)
      ischemic preconditioning (4 x 5 min). Thrombolysis with intracoronary recombinant
      tissue plasminogen activator produced reperfusion in 6.3 +/- 1.4 min (average for
      68 dogs). After restoration of blood flow, vessel patency was maintained for 4 h
      with the glycoprotein IIb/IIIa receptor antagonist, BIBU 52ZW. BIIB-722,
      administered before (26.9 +/- 3.6%) or after (22.0 +/- 2.3%) 60-min ischemia or
      preconditioning (18.4 +/- 2.8%), produced comparable and significant reductions
      in infarct size (percent of area at risk) compared to controls (47.2 +/- 2.0%).
      After 90 min of ischemia, BIIB-722 administered before occlusion (37.3 +/- 1.1%)
      and ischemic preconditioning (35.0 +/- 4.8%) provided significant
      cardioprotection compared to control (45.9 +/- 1.8%). BIIB-722 was not
      cardioprotective when administered during occlusion (48.0 +/- 2.4%). The results
      indicate that Na+/H+ exchange inhibition and preconditioning provide a comparable
      degree of cardioprotection against 60 min of regional ischemia. However, when the
      regional ischemic period is extended to 90 min, the degree of cardioprotection is
      markedly reduced. Further studies incorporating clinically relevant events such
      as thrombosis and thrombolysis are required before one can conclude that Na+/H+
      exchange inhibition is effective against more prolonged myocardial ischemia.

PMID- 16899992
TI  - A study on the outcome of percutaneous transluminal renal angioplasty in patients
      with renal failure.
AB  - BACKGROUND: The indications for percutaneous transluminal renal angioplasty
      (PTRA) in renovascular disease, as well as its benefits, remain a matter of
      debate. The aim of this study was to evaluate the outcome of angioplasty and to
      identify risk factors associated with less successful outcomes in patients with
      atheromatous renal artery stenosis and renal failure of varying degrees. METHODS:
      The results of PTRA were analyzed retrospectively in 144 patients with serum
      creatinine levels of >130 micromol/l. Patients were divided into 5 groups
      according to their indication for angioplasty: (1) deteriorating renal function;
      (2) accelerating hypertension; (3) a combination of 1 and 2; (4) peripheral
      vascular disease, and (5) miscellaneous conditions. RESULTS: The baseline mean
      (+/- SD) systolic and diastolic blood pressures of the entire group were lowered
      from 180 +/- 32 and 95 +/- 16 mm Hg to 162 +/- 23 and 86 +/- 12 mm Hg,
      respectively (p < 0.0005), 12 months after angioplasty. The blood pressure level
      was unaffected by angioplasty in patients with claudication. The mean number of
      antihypertensive drugs was reduced in the group with accelerating hypertension
      from 2.9 +/- 0.8 to 2.4 +/- 1.2 (p = 0.019), and in the group with unilateral
      renal artery stenosis and two kidneys from 2.4 +/- 1.0 to 1.8 +/- 1.1 (p =
      0.002), 12 months after PTRA. Glomerular filtration rate at 3-month follow-up had
      increased from 23 +/- 11 to 27 +/- 14 ml/min/1.73 m(2) (p = 0.021) in group 1,
      from 25 +/- 11 to 28 +/- 14 ml/min/1.73 m(2) (p = 0.031) in the combined group of
      patients consisting of groups 1 and 3, and from 32 +/- 13 to 35 +/- 14
      ml/min/1.73 m(2) (p = 0.019) in the group with unilateral renal artery stenosis.
      No statistically significant difference was found in any of these 3 groups 1 year
      after angioplasty. The first patient group had an increased prevalence of
      cardiovascular disease, aortic aneurysm, carotid occlusive disease, and
      peripheral vascular disease compared to the other patient groups (p < 0.05).
      Patients with baseline creatinine levels of >300 micromol/l had a lower survival
      rate at 12, 60, and 120 months after PTRA than patients with serum creatinine
      levels of <300 micromol/l (p < 0.005). Survival was also lower in patients with
      bilateral renal artery stenosis and those with a single kidney, compared to
      patients with a unilateral stenosis at both 5 and 10 years after PTRA (p < 0.05).
      Regression analysis of predictor variables of mortality rate showed that the
      relative risk (RR) associated with increased serum creatinine was 4.7 (CI 2.0
      11.0; p < 0.0005). The RR for older patients was 1.1 (CI 1.0-1.2; p = 0.008), and
      the RR for former smokers was 6.0 (CI 1.6-24.0; p = 0.009). CONCLUSION: The
      results of the present study indicate that glomerular filtration can be improved
      in patients who primarily undergo angioplasty to rescue renal function. Renal
      function with creatinine levels of >300 micromol/l was associated with a lower
      survival rate. It is, therefore, possible that patients selected after a thorough
      evaluation of their renal function and comorbid disease factors may benefit from
      PTRA, even when the indication for angioplasty is to salvage renal function.

PMID- 16899993
TI  - Renal effects of HMG-CoA reductase inhibition in a rat model of chronic
      inhibition of nitric oxide synthesis.
AB  - BACKGROUND/AIMS: In addition to their lipid-lowering effects, HMG-CoA reductase
      inhibitors (statins) induce a variety of pleiotropic actions that have been
      recently studied in the area of cardiovascular and renal protection. In the
      present studies we sought to determine whether statins retain beneficial effects
      in the experimental model of NO deficiency achieved by chronic administration of
      a pressor dose of L-arginine analogue N-nitro-L-arginine-methyl ester (L-NAME).
      METHODS: To address this issue, blood pressure (BP), renal function (GFR), and
      albuminuria were determined in rats treated for 4 weeks with L-NAME, L-NAME +
      atorvastatin (ATO), and in untreated controls. In addition, renal cortical
      protein expression of caveolin 1 (CAV1), vascular endothelial growth factor
      (VEGF), and activity of RhoA were also determined. RESULTS: L-NAME administration
      resulted in sustained elevation of BP, decreased GFR, and in higher albuminuria
      as compared to control animals. Co-administration of ATO with L-NAME normalized
      albuminuria and prevented decreases in GFR in L-NAME rats without having an
      impact on pressor effects of L-NAME. CAV1 protein expression was similar in all
      groups of rats. In contrast, VEGF expression and RhoA activity was increased in L
      NAME-treated animals, and normalized with co-administration of ATO. CONCLUSION:
      Treatment with ATO exerts early nephroprotective effects in the NO-deficient
      model of hypertension. These effects could be mediated by amelioration of VEGF
      expression and reduction of RhoA activity.

PMID- 16899994
TI  - Urokinase plasminogen activator in injured adventitia increases the number of
      myofibroblasts and augments early proliferation.
AB  - Myofibroblasts are involved in vessel remodeling during the development of
      hypertension as well as after angioplasty and aortocoronary grafting, but the
      mechanisms of myofibroblastic phenotypic modulation are not fully elucidated. We
      assessed the role of urokinase plasminogen activator (uPA) and its proteolytic
      activity in myofibroblast differentiation and the early proliferation following
      mechanical injury of the rat carotid adventitia. The effects of perivascular
      application of recombinant uPA (r-uPA), proteolytically inactive r-uPA(H/Q) and
      uPA neutralizing antibody were evaluated 4 days after surgical injury to the
      adventitia. The phenotype of adventitial cells was assessed using anti-alpha
      smooth muscle actin (alpha-SM actin) antibody, anti-SM heavy chain myosin, anti
      high-molecular-weight caldesmon, anti-smoothelin and anti-ED-1 antibodies,
      proliferation by the expression of proliferating cell nuclear antigen, and the
      size of the adventitia by quantitative morphometry. Four days after injury, the
      intensive immunostaining for urokinase appeared in the rat carotid artery
      adventitia. At the same time, the frequency of alpha-SM actin-positive
      adventitial cells was 1.8+/-1.1% in uninjured arteries and 25.2+/-5.4% in injured
      arteries (p<0.05), and the respective frequency of ED-1-positive cells 1.5+/-1.1
      and 25.0+/-5.2%. The application of exogenous r-uPA doubled the numbers of alpha
      SM actin-positive adventitial cells to 55.7+/-6.8% (p<0.05). ED-1-positive cells
      and proliferating cell nuclear antigen-positive cells as well as the size of the
      adventitia were also significantly increased after r-uPA compared with injury
      alone. In contrast, the proteolytically inactive r-uPA(H/Q) did not affect any
      parameters. The application of uPA neutralizing antibody attenuated the frequency
      of alpha-SM actin-positive cells to 12.6+/-3.5% (p<0.05), the frequency of ED-1
      positive cells, and the numbers of adventitial cells. r-uPA stimulation of
      cultured human skin fibroblasts significantly increased the alpha-SM actin
      content in a concentration-dependent manner. In contrast, r-uPAH/Q did not induce
      changes in alpha-SM actin content. We conclude that uPA, which is upregulated in
      the injured adventitia, can augment adventitial cell accumulation, including
      myofibroblasts, and adventitia growth early after injury of the rat carotid
      artery adventitia by mechanisms involving proteolysis.

PMID- 16899995
TI  - Effects of tibolone on sulfatase pathway of estrogens metabolism and on growth of
      MCF-7 human breast tumors implanted in ovariectomized nude mice.
AB  - BACKGROUND: The benefits of estrogen plus progestin in healthy post-menopausal
      women remain uncertain. Tibolone, with its in vitro documented inhibitory effects
      on estrogens metabolism and its selective action on breast, may be an alternative
      that could favorably influence the health benefit of hormone replacement therapy.
      METHODS: We studied the effect of tibolone on the tumor growth of MCF-7 cells
      implanted in 40 ovariectomized nude mice, receiving subcutaneous pellets of
      17beta-estradiol, estrone, estrone-sulfate or vehicle, and daily gavages of
      tibolone or placebo. RESULTS: Tibolone, although used at high dose, did not
      stimulate nor inhibit the estrogen-induced tumors, nor the tumors in estrogen
      deprived mice. Measurements of plasma levels of estrogens indicated that tibolone
      potently stimulated sulfotransferase activity, but intra-tumor levels of
      estrogens were not significantly modified by tibolone. CONCLUSIONS: This in vivo
      study performed with high dose of orally administered tibolone that allowed its
      hepatic conversion into active metabolites has shown no significant effect on
      breast tumors growth. Tibolone increased the circulating sulfated estrogens by
      its activity on the hepatic sulfation but not the intra-tumor levels of estrogens
      (free or sulfated). However, further studies of dose-response curve and molecular
      markers are needed to exclude definitely a stimulatory effect of tibolone on
      tumor growth.

PMID- 16899996
TI  - MMSE scores decline at a greater rate in frontotemporal degeneration than in AD.
AB  - The clinical diagnostic criteria for frontotemporal degeneration (FTD) include
      relative preservation of memory and visuospatial function, in contradistinction
      to characteristics of Alzheimer's disease (AD). The Mini-Mental State Examination
      (MMSE) contains items to assess these areas of cognition. In a retrospective case
      control study of participants at two institutionally-based AD centers, we
      determined whether total MMSE and MMSE subscores would reflect the disease
      progression projected by the clinical criteria of FTD vs. AD. Participants were
      44 subjects with FTD (7 pathologically confirmed) and 45 with pathologically
      confirmed AD. Each subject had at least two MMSEs with minimum inter-test
      intervals of 9 months. We compared annualized rates of change for total MMSE
      scores and cognitive domain subscores over time and between groups by two
      independent samples t-tests and proportion tests. The total MMSE score (p = 0.03)
      and language subscore (p = 0.02) showed a greater rate of decline for the FTD
      group than the AD group, although the constructional praxis item declined less
      rapidly in the FTD group (p = 0.018). Changes in MMSE subscores paralleled the
      clinical diagnostic criteria for FTD. The more rapid progression on the language
      subscore was observed in both language and behavioral variants of FTD.

PMID- 16899997
TI  - Beta-amlyoid 1-42 and tau-protein in cerebrospinal fluid of patients with
      Parkinson's disease dementia.
AB  - Measurement of tau-protein and beta-amyloid(1-42 )(Abeta42) in cerebrospinal
      fluid (CSF) has gained increasing acceptance in the differential diagnosis of
      Alzheimer's disease. We investigated CSF tau-protein and Abeta42 concentrations
      in 73 patients with advanced idiopathic Parkinson's disease with dementia (PDD)
      and 23 patients with idiopathic Parkinson's disease without dementia (PD) and in
      a comparison group of 41 non-demented neurological patients (CG) using
      commercially available enzyme-linked-immunoabsorbant-assay (ELISA). tau-Protein
      levels were statistically significantly higher and Abeta42 lower in the PDD
      patients compared to PD patients and the CG. This observation was most marked (p
      < 0.05) in a subgroup of patients with PDD carrying the apolipoprotein genotype
      epsilon3/epsilon3. The distribution of the apolipoprotein genotypes in PDD and PD
      patients was similar to that of the CG. Although a significant difference in tau
      protein values was observed between PDD and CG, no diagnostic cut-off value was
      established. These findings suggest that such protein CSF changes may help to
      support the clinical diagnosis of cognitive decline in PD and that there may be
      apolipoprotein-E-isoform-specific differences in CSF protein regulation in
      advanced PDD.

PMID- 16899998
TI  - Prospective memory complaints can be predicted by prospective memory performance
      in older adults.
AB  - BACKGROUND/AIMS: The aim of this study was to explore if prospective memory
      complaints reflect actual prospective memory performance in older adults.
      METHODS: Three hundred and sixty-four older adults aged 65-80 years were
      investigated with regard to prospective memory complaints, prospective memory
      test performance, self-reported depressive symptoms, and self-reported memory
      capacity. RESULTS: Separate analyses revealed that about half of the participants
      showed a significant relation between subjective and objective prospective
      memory. CONCLUSION: Older adults appear to be heterogeneous with regard to the
      association between objective and subjective prospective memory. For older adults
      with relatively few depressive symptoms and memory concerns, prospective memory
      complaints may serve as a valid criterion in the assessment of prospective memory
      ability.

PMID- 16899999
TI  - Variations in the BDNF gene in autopsy-confirmed Alzheimer's disease and dementia
      with Lewy bodies in Japan.
AB  - BACKGROUND/AIM: Brain-derived neurotrophic factor (BDNF) is associated with the
      hippocampus and the nigrostriatal dopaminergic function. Data showing that its
      level was reduced in Alzheimer's disease (AD) and Parkinson's disease (PD)
      suggested that the BDNF function must play an important role in the pathogenetics
      of these diseases. Indeed, variation in the BDNF gene may confer susceptibility
      to AD and PD development. Recently, a functional BDNF Val66Met polymorphism has
      been found to be associated with episodic memory and hippocampal function, with
      intracellular trafficking, and with activity-dependent secretion of BDNF. To
      date, there have been several conflicting reports on the correlation between AD
      or PD and Val66Met or C270T polymorphism in the BDNF promoter region, although no
      data on this relationship have been published with respect to dementia with Lewy
      bodies (DLB). In the present study, we investigated a possible association
      between such BDNF polymorphisms and susceptibility to AD or DLB. METHODS: BDNF
      genotyping was carried out by the polymerase chain reaction-restriction fragment
      length polymorphism method in autopsy-confirmed human samples. RESULTS AND
      CONCLUSION: On comparing patients and controls, the distribution of BDNF
      genotypes and alleles did not differ significantly. Our findings suggest that it
      is unlikely that these BDNF polymorphisms play a major role in the pathogenesis
      of AD and DLB in the Japanese population.

PMID- 16900000
TI  - Regional pattern of increased water diffusivity in hippocampus and corpus
      callosum in mild cognitive impairment.
AB  - BACKGROUND: Corpus callosum atrophy possibly indicates neuronal degeneration in
      association cortex in Alzheimer's disease (AD). Water diffusivity allows
      detecting physiological changes that probably occur earlier than structural
      shrinkage in cerebral regions during the development of AD. OBJECTIVE: To
      simultaneously investigate the focal volumetric and early structural changes with
      apparent diffusion coefficient (ADC) of corpus callosum in mild cognitive
      impairment (MCI), and to explore the regional pattern of ADC increase in
      hippocampus and corpus callosum. METHODS: Thirteen subjects with MCI and 13
      healthy age-matched control subjects were studied. With three-dimensional
      volumetric spoiled gradient recalled echo MRI images, we measured the volume of
      hippocampus and corpus callosum. Using MRI-guided diffusion-weighted imaging
      analysis, we calculated ADCs from hippocampus and corpus callosum. Within the
      receiver-operation curve (ROC) statistical framework, areas under ROC curves from
      hippocampal and callosal ADCs were compared in differentiating between MCI and
      controls. RESULTS: After normalization to intracranial volume, hippocampal, not
      callosal, volume was significantly reduced in MCI. ADC values were increased in
      hippocampus and corpus callosum in MCI. The extent of ADC increase was similar
      between hippocampus and corpus callosum. CONCLUSION: Alterations in water
      diffusivity may precede corpus callosum atrophy during the development of MCI.
      Diffusion changes might occur simultaneously in allocortex and neocortex in MCI.

PMID- 16900001
TI  - Vitamin D status and its relation to age and body mass index.
AB  - BACKGROUND/AIMS: While numerous studies have examined 25(OH)-vitamin D(3) (25-D)
      concentrations and their relation to parathyroid hormone (PTH) levels there is
      only limited information on the interrelation between 25-D, 1,25(OH)(2)-vitamin
      D(3) (1,25-D) and PTH. It was the aim of this study to assess the vitamin D
      endocrine system and its relation to age and body mass index (BMI). METHODS: This
      cross-sectional study comprised a convenience sample of 483 adults which attended
      the endocrinology outpatient service of a university hospital in the years 2002
      2004. RESULTS: The mean concentrations of 25-D, 1,25-D, calcium and PTH were 21.0
      +/- 10.6 ng/ml, 47.9 +/- 21.7 pg/ml, 9.48 +/- 0.48 mg/dl and 51.0 +/- 27.2 pg/ml,
      respectively. 25-D was related (p < 0.01) to BMI, age, PTH and 1,25-D. After
      correction for 25-D, we found no relation between BMI and 1,25-D. PTH was related
      (p < 0.01) to serum calcium, BMI, age and 1,25-D (p = 0015). There was a seasonal
      variation in both, 25-D and 1,25-D serum concentrations: 25-D levels were lowest
      in January and increased until July while the nadir and zenith of 1,25-D were
      found in April and October, respectively. CONCLUSION: Since BMI was negatively
      related to 25-D the prevalence of 25-D deficiency (<8.8 ng/ml) increased from
      8.8% in subjects with BMI <30 kg/m(2) to 15.0% in subjects with BMI >30 kg/m(2).
      BMI, age and season should be taken into account when assessing a patients
      vitamin D status and more aggressive vitamin D supplementation should be
      considered for obese subjects.

PMID- 16900004
TI  - Integrated backscatter for the assessment of myocardial viability.
AB  - PURPOSE OF REVIEW: Ultrasonic tissue characterization is a non-invasive
      diagnostic method that uses myocardial integrated backscatter analysis to
      determine contractile performance and myocardial viability independent of wall
      motion. This review discusses recent clinical findings regarding the application
      of ultrasonic tissue characterization for the assessment of myocardial viability.
      RECENT FINDINGS: As this technique is non-invasive, ultrasonic tissue
      characterization can be used to predict the patency of infarct-related arteries
      in patients in the early stage of acute myocardial infarction. Several recent
      studies have shown that this technique is useful in identifying myocardial
      contractile reserve. The accuracy of ultrasonic tissue characterization for
      predicting functional recovery after coronary reperfusion is comparable to
      dobutamine echocardiography and radionuclide methods. Several studies have
      suggested that the cyclic variation of myocardial integrated backscatter reflects
      myocardial viability rather than contractile reserve. The cyclic variation of
      integrated backscatter is associated with myocardial viability confirmed by the
      integrity of the microvasculature identified by contrast echocardiography. In
      addition, the cyclic variation of integrated backscatter better reflects
      myocardial viability confirmed by the integrity of cellar metabolism than
      contractile reserve. SUMMARY: Ultrasonic tissue characterization with integrated
      backscatter is a useful non-invasive method that can provide unique information
      for the assessment of myocardial viability.

PMID- 16900002
TI  - Allopurinol and enalapril failed to conserve urinary NOx and sodium in ischemic
      acute renal failure in spontaneously hypertensive rats.
AB  - BACKGROUND: Ischemia-reperfusion-induced acute renal failure (ARF) is associated
      with a high mortality in patients with hypertension and with an unfavorable
      outcome of kidney transplants from marginal donors. AIM: The influence of
      allopurinol and enalapril on urinary nitrate/nitrite (UNOx), glomerular
      filtration rate, plasma and urinary sodium, and hemodynamic parameters was
      examined in spontaneously hypertensive rats (SHR) with ARF. METHODS: ARF was
      induced by right-kidney removal and clamping the left renal artery for 40 min in
      50 male 26-week-old SHR weighing 300 +/- 23 g. The rats were randomly allocated
      to five groups: (1) sham operated; (2) ARF; (3) ARF after pretreatment with 40
      mg/kg allopurinol; (4) ARF after pretreatment with 40 mg/kg enalapril, and (5)
      ARF after pretreatment with 40 mg/kg allopurinol and 40 mg/kg enalapril.
      Creatinine clearance, UNOx (Griess reaction), cardiac output (dye dilution
      technique), mean arterial blood pressure, and renal blood flow were measured 24 h
      after reperfusion. Total vascular resistance and renal vascular resistance were
      calculated and compared between the groups. RESULTS: A nonsignificant decrease
      was found in both daily UNOx excretion and creatinine clearance when pretreated
      ARF groups and the ARF group without pretreatment were compared (p > 0.05).
      Significantly lower plasma sodium values (139.5 +/- 4.86 mmol/l) in the
      allopurinol-pretreated ARF group were found than in the ARF group without
      pretreatment, in the ARF group pretreated with enalapril, and in the sham SHR
      group (p = 0.029). The urinary sodium loss was greater in the enalapril
      pretreated than in the allopurinol-pretreated ARF group (p = 0.047). Allopurinol
      and/or enalapril pretreatment decreased total vascular resistance (p = 0.003) in
      comparison with the sham SHR group. CONCLUSION: Neither allopurinol nor enalapril
      nor both were protective against ischemia-reperfusion injury in SHR, nor altered
      glomerular filtration rate and UNOx in a favorable direction.

PMID- 16900005
TI  - Tissue Doppler and innovative myocardial-deformation imaging techniques for
      assessment of myocardial viability.
AB  - PURPOSE OF REVIEW: Visual analysis of stress echocardiography allows evaluation
      of myocardial viability in acutely and chronically impaired left-ventricular
      function. Tissue Doppler and derived echocardiographic imaging techniques provide
      a tool for quantification of regional left-ventricular function which overcomes
      the limitations of subjective, experience-dependent reading of stress
      echocardiography. RECENT FINDINGS: Regional systolic and diastolic myocardial
      velocities as well as the derived myocardial-deformation parameters strain and
      strain rate are impaired in patients with left-ventricular dysfunction. Increase
      of myocardial velocities, strain and strain rate during stress stimulation are
      indicators of functional reserve in viable segments, while failure to increase
      indicates nonviability. Previous studies with very precise determination of
      regional myocardial deformation have shown that even analysis of resting function
      without evaluation of the functional reserve during stimulation allows assessment
      of myocardial viability. New two-dimensional echocardiography-based tissue
      tracking techniques yield an angle-independent imaging modality that is likely to
      further improve the clinical applicability of echocardiographic imaging
      techniques to define regional myocardial viability. SUMMARY: This review attempts
      to define the role of tissue Doppler and new innovative myocardial-deformation
      imaging techniques for identification of myocardial viability in patients with
      impaired left-ventricular function.

PMID- 16900006
TI  - Prognostic role of dobutamine stress echocardiography in myocardial viability.
AB  - PURPOSE OF REVIEW: The aim of this review is to provide a perspective on the role
      of dobutamine stress echocardiography to evaluate myocardial viability and assess
      prognosis in patients with ischemic left ventricular dysfunction. RECENT
      FINDINGS: Pooled analysis of currently available data demonstrates that
      dobutamine stress echocardiography provides useful information on recovery of
      dysfunctional but viable myocardium and prognosis. In fact, improvement of long
      term prognosis may be the ultimate clinical challenge in the management of
      patients with ischemic left ventricular dysfunction. Dobutamine stress
      echocardiography can be used to assess residual ischemia and contractile reserve,
      which are significant determinants of prognosis. Additionally, other
      echocardiographic variables, such as end-diastolic wall thickness, end-systolic
      volume, and extent of viability, affect outcome after revascularization in
      patients with ischemic cardiomyopathy. SUMMARY: Dobutamine stress
      echocardiography provides information on myocardial ischemia, contractile
      reserve, and other prognostically relevant parameters in patients with ischemic
      left ventricular dysfunction. This information can be used to select the optimal
      treatment strategy for these patients and to estimate and improve clinical
      outcome.

PMID- 16900007
TI  - Assessment of myocardial viability by radionuclide and echocardiographic
      techniques: is it simply a sensitivity and specificity issue?
AB  - PURPOSE OF REVIEW: The assessment of myocardial viability provides important
      information that may guide therapeutic decisions in patients with coronary artery
      disease and left ventricular dysfunction. This review describes methods for
      assessing myocardial viability using single-photon emission computed tomography,
      with an emphasis on how to optimize the detection of viable myocardium using
      current techniques. Relevant comparisons of radionuclide techniques with
      echocardiographic methods are also discussed. RECENT FINDINGS: The basis for the
      assessment of myocardial viability using radionuclides is reviewed briefly.
      Radionuclide techniques provide important prognostic information that may affect
      the decision on if patients with coronary artery disease should be revascularized
      or treated medically. Data suggest that dobutamine stress echocardiography may
      underestimate viability in certain patients. Radionuclide techniques that assess
      both radiotracer uptake and ventricular function can provide a comprehensive
      approach to detect viable myocardium in most patients. SUMMARY: The methods for
      assessing myocardial viability using single-photon emission computed tomography
      are accurate, reproducible, and widely available. Viability testing should be
      considered in patients with known coronary artery disease and left ventricular
      dysfunction. Further studies are warranted to assess the affect of viability
      assessment on clinical outcomes.

PMID- 16900008
TI  - Prognostic role of single-photon emission computed tomography (SPECT) imaging in
      myocardial viability.
AB  - PURPOSE OF REVIEW: Cardiac imaging is evolving rapidly. Appropriate use of this
      technology could reduce morbidity and mortality, but inappropriate use could have
      a significant financial burden. Single-photon emission computed tomography
      imaging is widely available. This review summarizes the clinical utility and
      limitations of the prognostic role of single-photon emission computed tomography
      imaging for myocardial viability in patients with coronary artery disease and
      left-ventricular dysfunction. RECENT FINDINGS: 201Tl single-photon emission
      computed tomography, 99mTc single-photon emission computed tomography with
      sestamibi or tetrofosmin, and 18F-fluorodeoxyglucose single-photon emission
      computed tomography are validated tools for assessing myocardial viability. These
      techniques have a very similar predictive value in determining regional and
      global response to revascularization. 201Tl single-photon emission computed
      tomography viability studies are predictive of reverse left-ventricular
      remodeling, symptom improvement, and patient outcome after revascularization.
      Combination imaging with dual-isotope simultaneous acquisition single-photon
      emission computed tomography or positron-emission tomography/single-photon
      emission computed tomography may improve the positive and negative predictive
      values of single-photon emission computed tomography-based viability studies.
      SUMMARY: Single-photon emission computed tomography-based myocardial viability
      testing is an important diagnostic modality due to widespread availability and
      reasonably good sensitivity and specificity for detecting viable myocardium and
      predicting clinical and functional responses to revascularization. In the future
      single-photon emission computed tomography viability techniques may have a
      prognostic role in predicting responses to cardiac resynchronization therapy and
      evaluating myocardial stem-cell transplantation.

PMID- 16900010
TI  - Magnetic resonance for the assessment of myocardial viability.
AB  - PURPOSE OF REVIEW: Cardiac magnetic resonance imaging has an expanding role as a
      preferred modality for the detection and characterization of myocardial
      viability. RECENT FINDINGS: Improving the accuracy of cardiac magnetic resonance
      for detecting viable myocardium has been one focus of investigators. In segments
      with intermediate transmurality of late gadolinium enhancement, dobutamine
      response improves the predictive power of cardiac magnetic resonance. A
      subtractive imaging technique with both short and long inversion times can
      enhance discrimination of subendocardial infarction and blood pool, but with
      increased noise and misregistration artifacts. Similar pharmacokinetics between
      cardiac magnetic resonance contrast agents and computed tomography contrast
      allows delayed enhancement imaging with computed tomography. Contrast between
      normal segments and scar remains vastly superior with cardiac magnetic resonance
      and no radiation is administered. Quantitation of blood flow demonstrated that
      resting myocardial blood flow is reduced in hibernating myocardium. SUMMARY:
      Because of its safety, accuracy, ease of interpretation, and increasing
      availability, cardiac magnetic resonance-based assessment of myocardial viability
      has quickly transitioned from bench to bedside. Routine clinical implementation
      has prompted improved diagnostic capabilities and easier image interpretation. As
      a research tool, cardiac magnetic resonance continues to provide valuable
      insights into the fundamental nature of viability.

PMID- 16900009
TI  - Positron emission tomography for assessment of viability.
AB  - PURPOSE OF REVIEW: The recent success of magnetic resonance imaging for viability
      assessment has raised questions about the future role of positron emission
      tomography and older imaging modalities in the assessment of viability. Recent
      information, however, indicates that positron emission tomography will remain a
      valuable tool. RECENT FINDINGS: The primary positron emission tomography tracer
      used for assessment of viability is 18F-fluorodeoxyglucose, a glucose analogue
      that exhibits enhanced uptake in ischemic tissue. The finding of enhanced 18F
      fluorodeoxyglucose uptake and a relative reduction in perfusion is considered the
      positron emission tomography correlate of myocardial hibernation. The mismatch
      pattern has been shown to identify patients with improvement in systolic
      function, heart failure symptoms, and prognosis with revascularization. Mismatch
      identifies a subset of patients with vulnerable myocardium who have a higher
      likelihood of a cardiac event compared with those without significant mismatch.
      Delay in revascularization may pose extra risk for those with mismatch. Positron
      emission tomography and magnetic resonance imaging demonstrate a close
      correlation in the detection of viable myocardium. The development of combined
      positron emission tomography/computed tomography scanners can reduce imaging time
      and improve functional-anatomic correlations. SUMMARY: Positron emission
      tomography imaging utilizing 18F-fluorodeoxyglucose and perfusion tracers
      provides valuable diagnostic and prognostic information in patients with ischemic
      left ventricular dysfunction and has comparable accuracy to competing
      technologies for detection of viability.

PMID- 16900011
TI  - Contrast echocardiography for the assessment of myocardial viability.
AB  - PURPOSE OF REVIEW: The availability of an accurate, non-invasive method for
      distinguishing viable from irreversibly damaged myocardium, after acute
      myocardial infarction or in chronic coronary artery disease, is important in
      clinical decision making. Such a tool would enable physicians to identify
      patients most likely to benefit from revascularization strategies in patients
      with coronary artery disease and left ventricular dysfunction. Myocardial
      contrast echocardiography is a new technique that utilizes acoustically active
      gas-filled microspheres (microbubbles), which remain exclusively in the
      intravascular space and allow the simultaneous assessment of global and regional
      myocardial structure, function, and perfusion. An increasing body of data
      supports its role in assessing myocardial viability and predicting the recovery
      of function. RECENT FINDINGS: Myocardial contrast echocardiography accurately
      differentiates 'stunning' from necrosis, delineates transmural extent of
      infarction, predicts recovery of regional and global left ventricular systolic
      function in the recuperative phase, identifies patients at high risk of left
      ventricular remodelling, and provides incremental viability data when performed
      in conjunction with low-dose dobutamine echocardiography. SUMMARY: Technological
      advances have positioned myocardial contrast echocardiography as a safe,
      practical bedside technique for the evaluation of myocardial viability. It has
      comparable accuracy with other non-invasive imaging techniques, such as
      dobutamine stress echocardiography, radionuclide scintigraphy and cardiac
      magnetic resonance imaging.

PMID- 16900013
TI  - Treatment of hypertension based on measurement of blood pressure variability:
      lessons from animal studies.
AB  - PURPOSE OF REVIEW: Blood pressure variability, a quantitative index for the
      spontaneous variation in blood pressure, has been proposed as a risk factor for
      end-organ damage and to determine the efficacy of hypertension treatment. RECENT
      FINDINGS: Animal studies indicate that blood pressure variability is as important
      as blood pressure level in determining end-organ damage, and that high blood
      pressure variability is associated with end-organ damage, including myocardial
      lesions, aortic hypertrophy, vascular remodeling and renal damage. Although the
      organ damage induced by high blood pressure variability was similar to that
      induced by hypertension, comparative studies in sinoaortic-denervated and
      spontaneously hypertensive rats revealed that aortic hypertrophy is a sensitive
      index of high blood pressure variability, and left ventricular hypertrophy is a
      sensitive index of high blood pressure level. The possible mechanisms for high
      blood pressure variability-induced end-organ damage include: direct endothelial
      lesions, renin-angiotensin system activation, inflammation initiation and
      cardiomyocyte apoptosis augmentation. Blood pressure variability reduction
      contributes importantly to the organ-protective effect of some antihypertensive
      drugs. SUMMARY: Although animal studies suggest some advantages in blood pressure
      variability measurements, clinical trials are necessary before the widespread use
      of blood pressure variability as a predictor of hypertensive organ damage and a
      new strategy for the treatment of hypertension.

PMID- 16900012
TI  - The prevention and treatment of metabolic syndrome and high-risk obesity.
AB  - PURPOSE OF REVIEW: The prevalence of obesity is increasing at an alarming rate,
      and the obesity epidemic is driving the epidemic in type 2 diabetes. High-risk
      obesity is characterized by abdominal obesity with evidence of abnormal glucose
      and lipid metabolism, and a state of heightened inflammation. RECENT FINDINGS:
      With increasing body weight, lipid accumulation occurs not only in adipose
      tissue, but in other organs as well. This 'lipotoxicity' in liver, muscle,
      islets, and elsewhere may account for many of the features of the metabolic
      syndrome. Adipose tissue produces many proteins, some of which are inflammatory
      cytokines, and others of which are antiinflammatory or which improve insulin
      sensitivity. SUMMARY: The treatment of obesity requires the identification of the
      high-risk patient, and the institution of lifestyle measures with a long-term
      outlook, and an avoidance of heavily marketed fads. Current research will likely
      lead to improved medications in the future.

PMID- 16900014
TI  - Current strategies for the prevention of angina in patients with stable coronary
      artery disease.
AB  - PURPOSE OF REVIEW: Angina pectoris affects at least 6.6 million people in the US
      and approximately 400,000 new cases of stable angina occur each year. Angina may
      be one of the first signs of ischemic heart disease, although it is likely not
      causally related to the likelihood of plaque rupture leading to an acute coronary
      syndrome. Modalities for treatment of angina should be used maximally to improve
      quality of life and decrease cardiovascular morbidity and mortality. The current
      recommended pharmacologic and invasive approaches, as well as novel therapies,
      are reviewed. RECENT FINDINGS: Antiischemic agents, including beta-blockers,
      nitrates and calcium channel blockers, remain the mainstay in the prevention of
      angina. Revascularization via percutaneous interventions or coronary bypass
      surgery are appropriate in specific cases or when medical treatment fails.
      Noninvasive treatment options for refractory angina, metabolic agents, and
      vasodilator therapies are adding to the armamentarium to prevent and treat
      angina. SUMMARY: A multifaceted approach is optimal to address the prevention of
      angina. Once angina is recognized, there are many modalities that lessen the
      incidence of daily life-induced and exercise-induced angina and ischemia. Angina
      management is best addressed by pharmacologic and lifestyle interventions.

PMID- 16900015
TI  - Prevention of myocardial infarction.
AB  - PURPOSE OF REVIEW: There is an enormous literature on the prevention of
      myocardial infarction. However, most articles are focused categorically on
      evidence-based medicine and give no room for conceptual analyses. In this
      article, we attempt to review the main aspects of this theme from a different
      point of view. RECENT FINDINGS: In the last decade, scientists have encouraged
      the understanding and gradual application of genetics in the study of common
      diseases. This is one of the main angles from which we try to review the
      prevention of myocardial infarction. Another important factor is the
      consideration of cost-effectiveness. Consequently, we remark on the value of
      interventions that can have an impact on cost. SUMMARY: In preventing myocardial
      infarction modern physicians should emphasize the importance of behavioral and
      cultural changes and learn from genetic advances in restoring the delicate
      balance that is altered in atherosclerotic disease.

PMID- 16900016
TI  - Prevention of heart failure.
AB  - PURPOSE OF REVIEW: Chronic heart failure imposes a significant health burden and
      remains a substantial and increasing problem despite advances in therapy. Hence,
      prevention of heart failure is a priority. RECENT FINDINGS: Various risk factors
      have been identified that contribute to the development of heart failure. In this
      review, we will discuss the various recently reported clinical trials,
      epidemiological studies, meta-analyses, and subanalyses that have identified
      these risk factors and have provided evidence regarding the strategies to prevent
      heart failure. SUMMARY: Heart failure is a costly, disabling, and potentially
      fatal disease. It is therefore important to incorporate the strategies for
      prevention of heart failure on the basis of the current available evidence into
      routine clinical practice.

PMID- 16900017
TI  - Sudden death secondary to cardiac arrhythmias: mechanisms and treatment
      strategies.
AB  - PURPOSE OF REVIEW: This article reviews mechanisms and available therapeutic
      options for arrhythmias leading to sudden cardiac death in patients with coronary
      artery disease. RECENT FINDINGS: Intensive efforts have led to a better
      understanding of the pathophysiology and various treatments of sudden cardiac
      death. Antiarrhythmic medications have not demonstrated a survival benefit. Beta
      adrenergic blocking agents have been revalidated in recent studies to improve
      survival and reduce risk of sudden cardiac death in patients with myocardial
      infarction. Angiotensin-converting enzyme inhibitors and aldosterone antagonists
      should also be used in these patients. Data from randomized trials demonstrate
      significant survival benefit with an implantable cardioverter-defibrillator and
      indications have expanded. Patients with established ischemic cardiomyopathy do
      not require electrophysiologic studies for induction of tachyarrhythmias based on
      these trials. One recent trial did not demonstrate mortality reduction with
      implantable defibrillators in patients with recent myocardial infarction. Devices
      may not provide survival benefit in patients with advanced New York Heart
      Association class IV heart failure. SUMMARY: The incidence of arrhythmia-related
      sudden death in the general population remains relatively high. Better risk
      stratification tools are needed to identify high-risk patients in the general
      population and in those with known coronary disease and to exclude low-risk
      patients.

PMID- 16900019
TI  - An evidence-based approach to the management of pulmonary arterial hypertension.

PMID- 16900020
TI  - Bibliography. Current world literature. Imaging and echocardiography.

PMID- 16900022
TI  - Diagnosis and management of Acanthamoeba keratitis.
AB  - PURPOSE OF REVIEW: This paper reviews the literature generated on Acanthamoeba
      keratitis since 1998. RECENT FINDINGS: Acanthamoeba infections may be on the
      rise. Contact lenses are the biggest risk factor for their development. Silicone
      hydrogel lenses are increasingly prescribed and may be 'more sticky' to
      Acanthamoeba organisms. Orthokeratology for the treatment of myopia has been
      associated with many new cases of Acanthamoeba keratitis. Daily disposable
      contact lenses are the safest form of soft contact lens. Patients continue to be
      misdiagnosed as having herpetic keratitis. Impression cytology and confocal
      microscopy are newer diagnostic modalities. Topical polyhexamethylene biguanide,
      chlorhexidine and propamidine are the mainstay of medical therapy. Amniotic
      membrane may be used for cases of persistent epithelial defect and to control
      inflammation. Penetrating keratoplasty in a medically treated eye affords a good
      chance of positive outcome. SUMMARY: Acanthamoeba keratitis continues to be a
      difficult infection to diagnose and manage. The frequency of these infections may
      be on the rise, most commonly associated with frequent replacement soft contact
      lenses. The best chance for a good outcome is based on early diagnosis, so it is
      important for ophthalmologists consider it in patients, especially in the contact
      lens wearer with suspected herpes simplex keratitis.

PMID- 16900023
TI  - Preserving the cornea: corneal storage media.
AB  - PURPOSE OF REVIEW: The aim of this article is to review the recent literature
      regarding corneal storage media since the last review that discussed this topic
      in substantial detail in this journal. RECENT FINDINGS: During the last few
      years, despite the development of new corneal storage media and the addition of
      new additives to established corneal storage media, Optisol GS (Bausch & Lomb,
      Irvine, California, USA) has continued to remain the popular choice among storage
      media used in the United States, and traditional organ culture methods are still
      used in Europe. Recognizing that persistent epithelial defects after corneal
      transplantation can be a serious complication, however, attention has started to
      focus on not only preserving the endothelium, but also the epithelium. In
      addition, there has been more research towards antimicrobial prophylaxis.
      SUMMARY: With recent evidence suggesting that longer storage times may allow
      better outcomes in high-risk grafts because of the depletion of donor T cells
      from the donor cornea into the storage media, storage media will need to be
      optimized for preserving the endothelium for longer periods of time. In addition,
      because the epithelium is typically unable to be sustained for longer than 1 week
      in storage media, research toward preserving the epithelium will also be
      essential.

PMID- 16900024
TI  - Corneal structure and biomechanics: impact on the diagnosis and management of
      glaucoma.
AB  - PURPOSE OF REVIEW: Highlights recent studies relating to the impact of corneal
      structure and biomechanical properties on glaucoma evaluation and management.
      RECENT FINDINGS: Central corneal thickness has been shown to play a role in the
      interpretation of intraocular pressure. Central corneal thickness has also been
      suggested as a glaucoma risk factor. The potential role of other corneal factors,
      such as stromal makeup, in the accurate measurement of intraocular pressure and
      the assessment of glaucoma risk remains to be determined. SUMMARY: Improved
      understanding of central corneal thickness and corneal biomechanical properties
      may someday lead to a better understanding of glaucoma risk and its assessment.

PMID- 16900025
TI  - Update on ocular graft versus host disease.
AB  - PURPOSE OF REVIEW: To summarize recent findings regarding the clinical spectrum,
      pathophysiology, and treatment of ocular graft versus host disease. RECENT
      FINDINGS: Ocular graft versus host disease is a common sequela of allogeneic
      hematopoietic transplantation affecting up to 80% of chronic graft versus host
      disease patients. Clinical features of ocular graft versus host disease encompass
      all parts of the eye, from the lid to the choroids, although ocular graft versus
      host disease is most commonly viewed as a disease of the ocular surface, with the
      conjunctiva and lacrimal gland most commonly affected. Clinical features of
      ocular graft versus host disease (keratoconjunctivitis sicca, cicatricial
      conjunctivitis, scleritis, and others) mirror other inflammatory ocular
      conditions associated with autoimmune/collagen vascular diseases.
      Immunohistochemistry studies of lacrimal gland dysfunction and conjunctival
      inflammation in chronic ocular graft versus host disease are summarized. Current
      diagnosis and treatment of chronic graft versus host disease are outlined in the
      recent publications from the National Institute of Health Chronic graft versus
      host disease Consensus Workshops, and the information relevant to ocular graft
      versus host disease is delineated. SUMMARY: Ocular graft versus host disease
      evaluation, diagnosis, and management should be approached in a multidisciplinary
      fashion in the context of the patient's overall graft versus host disease status.

PMID- 16900026
TI  - Deep anterior lamellar keratoplasty.
AB  - PURPOSE OF REVIEW: Recent advances in surgical technique have promoted a paradigm
      shift in the surgical treatment of corneal disease. Penetrating keratoplasty is
      now being replaced by various types of lamellar techniques that aim to replace
      damaged tissue only, while maintaining healthy tissue intact. This review focuses
      on recent advances in deep anterior lamellar keratoplasty. RECENT FINDINGS: The
      concept of creating a deep lamellar bed for lamellar keratoplasty is not new, but
      exposing Descemet's membrane was a tedious, time consuming procedure. New
      techniques that use air and ophthalmic viscosurgical devices to directly expose
      Descemet's membrane have dramatically reduced surgery time, while improving the
      safety of performing surgery. The indications for deep anterior lamellar
      keratoplasty have expanded from keratoconus and hereditary dystrophies, to
      include severe ocular surface disease and cases following infection and corneal
      perforation. SUMMARY: Deep anterior lamellar keratoplasty can be considered as
      the first choice of surgery for a wide range of corneal disease, with bullous
      keratopathy as the only absolute contraindication.

PMID- 16900027
TI  - Crosslinking treatment of progressive keratoconus: new hope.
AB  - PURPOSE OF REVIEW: A new method has been introduced for the treatment of
      progressive keratoconus using collagen crosslinking by the photosensitzer
      riboflavin and ultraviolet A-light. Biomechanical measurements have shown an
      impressive increase in corneal rigidity of 328.9% in human corneas after
      crosslinking. RECENT FINDINGS: The 3 and 5-year results of the Dresden clinical
      study have shown that in all treated 60 eyes the progression of keratoconus was
      at least stopped ('freezing'). In 31 eyes there also was a slight reversal and
      flattening of the keratoconus by up to 2.87 diopters. Best corrected visual
      acuity improved slightly by 1.4 lines. So far, over 150 keratoconus patients have
      received crosslinking treatment in Dresden. Laboratory studies have revealed that
      the maximum effect of the treatment is in the anterior 300 mum of the cornea. As
      for the corneal endothelium, a cytotoxic level for endothelium was found to be
      0.36 mW/cm which would be reached in human corneas with a stromal thickness of
      less than 400 mum. SUMMARY: Collagen crosslinking by the photosensitzer
      riboflavin and ultraviolet A-light is an effective means for stabilizing the
      cornea in keratoconus. Collagen crosslinking might become the standard therapy
      for progressive keratoconus in the future diminishing significantly the need for
      corneal transplantation. Preoperative pachymetry and individual control of the
      ultraviolet A-irradiance before each treatment are mandatory. The treatment
      parameters must not be varied.

PMID- 16900028
TI  - Genetics of corneal dystrophies: the evolving landscape.
AB  - PURPOSE OF REVIEW: Major advances and developments in corneal molecular genetics
      have revolutionized our fundamental understanding of corneal dystrophies. At the
      same time, this knowledge is allowing for improved ways to classify these
      dystrophies. New genes and mutations responsible for corneal dystrophies are
      being discovered at an accelerating rate. Ophthalmologists must keep abreast of
      all the new information, as our basic understanding as well as our classification
      systems are changing. We present a current review of the genetics of corneal
      dystrophies. RECENT FINDINGS: After the discovery of the BIGH3 (TGFbeta1) gene
      responsible for several corneal dystrophies, there has been an explosion of new
      information. New mutations are discovered every day for many of the corneal
      dystrophies located on the BIGH3 gene. In addition, new genetic sites are also
      being realized. Additionally, corneal dystrophies which have never been linked to
      any genetic site are now beginning to be uncovered. SUMMARY: As new mutations and
      genetic sites are discovered for the various corneal dystrophies, new information
      will arise, allowing researches to develop innovative methods to study these gene
      products and their function. This will open the door for novel diagnostic and
      therapeutic approaches. Ultimately, gene therapy may be possible, leading to
      cures for these sight-threatening diseases.

PMID- 16900030
TI  - Advances in refractive surgery: microkeratome and femtosecond laser flap creation
      in relation to safety, efficacy, predictability, and biomechanical stability.
AB  - PURPOSE OF REVIEW: Methods of flap creation have changed over the years from the
      evolution of the mechanical microkeratome to the introduction of the IntraLase
      femtosecond laser keratome, both of which have different mechanisms of action to
      create corneal resections. Previous studies report the advantages and
      disadvantages of the mechanical microkeratome and the IntraLase femtosecond
      laser. The critical components in laser in-situ keratomileusis surgery remain the
      same, however: safety, efficiency, predictability, and biomechanical stability.
      RECENT FINDINGS: Keratoectasia and flap efficiency remain a constant safety
      concern in laser in-situ keratomileusis surgery. Unexpectedly thick flaps as well
      as variable thickness continue to be a concern with safety in relation to
      microkeratome technology. Epithelial preservation, flap complications, and newer
      issues such as Transient Light Sensitivity Syndrome are safety concerns of flap
      creation. Improved outcomes with regards to vision, induced astigmatism, induced
      higher-order aberrations, and enhancement rates are seen to favor predictability
      of femtosecond technologies over the microkeratome. Recent biomechanical studies
      show improved healing with femtosecond laser flap creation compared with blade
      assisted flap creation. SUMMARY: The aim of this review is to summarize the key
      components for both the microkeratome and the femtosecond laser and to update on
      the recent advances reported on these topics.

PMID- 16900031
TI  - Pupil size and corneal laser surgery.
AB  - PURPOSE OF REVIEW: The role of scotopic pupil size as a factor in predicting
      night vision complaints is controversial. This review summarizes reports in the
      literature, some that have found and some that have failed to find a correlation
      with scotopic pupil size and night vision complaints. RECENT FINDINGS: Pupil
      measuring devices are discussed along with informed consent issues and reports
      showing that wavefront aberrations increase with increasing pupil size. A new
      objective measuring device (Larson) showed a correlation with postoperative
      starbursts and pupil size and a decrease in starbursts with wavefront-guided
      treatments compared with conventional excimer laser treatments. Cortical
      adaptation allows many patients to adapt to their new night vision. Treatment
      options for those who remain symptomatic include drops to reduce pupil size and
      wavefront-guided retreatments. SUMMARY: Reports in the literature are
      conflicting, and refractive surgeons would be wise to inform their patients that
      large scotopic pupil size is a potential risk factor for night vision complaints.
      By doing this they will follow the recommendations in recent patient information
      brochures of both VISX (Santa Clara, California) and Alcon (Orlando, Florida) and
      on the United States Food and Drug Administration web site.

PMID- 16900032
TI  - How has confocal microscopy helped us in refractive surgery?
AB  - PURPOSE OF REVIEW: To summarize the known uses of in-vivo confocal microscopy in
      refractive surgery, highlighting the current developments in the field. RECENT
      FINDINGS: Examination of the cornea after laser in-situ keratomileusis
      demonstrated that the keratocyte density within the laser in-situ keratomileusis
      flap and anterior residual corneal bed continued to decline during the entire 3
      year period of the study. The progressive loss of keratocytes in the flap and
      anterior portion of the residual corneal bed could have long-term implications in
      terms of corneal stability, refractive stability and cellular integrity after
      laser in-situ keratomileusis. Additional studies showed that the density of sub
      basal nerves decreased by 90% 1 month after laser in-situ keratomileusis. At some
      point between 3 and 6 months after laser in-situ keratomileusis, the sub-basal
      nerves began to recover and by 2 years they had reached approximately 50% of
      their original preoperative density. Analysis of sub-basal nerve density after
      photorefractive keratectomy reported that the nerve density completely recovered
      to preoperative levels by 2 years. Other confocal microscopic studies
      demonstrated that the microscope can detect infectious organisms in vivo, without
      stains or dyes. SUMMARY: The confocal microscope is a unique diagnostic
      instrument that can be used to evaluate corneal healing, long-term stability and
      to assess complications after refractive surgery. The ability of the device to
      view in-vivo cellular detail, microorganisms, inflammatory cells, epitheliod
      cells, fibrosis and measure the postoperative thickness of the residual corneal
      bed after laser in-situ keratomileusis, in a noninvasive manner, highlights the
      unique capabilities of this instrument.

PMID- 16900033
TI  - Epipolis laser in-situ keratomileusis: an evolving surface ablation procedure for
      refractive corrections.
AB  - PURPOSE OF REVIEW: The aim of this article is to provide an update on epipolis
      laser in-situ keratomileusis--an alternative surface photorefractive surgical
      technique for the correction of myopia. RECENT FINDINGS: In-vivo studies on
      animal models provide evidence that the replacement of the epithelial sheet on an
      ablated cornea can control corneal wound healing. Preliminary clinical data
      confirm that epipolis laser in-situ keratomileusis can provide excellent long
      term visual and refractive results. The problems of late visual rehabilitation
      and postoperative pain, however, have not yet been fully addressed. SUMMARY:
      Being a recently introduced surgical photorefractive technique for ametropias
      correction, epipolis laser in-situ keratomileusis is a fast evolving area of
      interest for refractive surgeons.

PMID- 16900034
TI  - Corneal reshaping: is it a good alternative to refractive surgery?
AB  - PURPOSE OF REVIEW: To review current literature on overnight corneal reshaping
      and present this mode of vision correction in its current state. RECENT FINDINGS:
      Overnight corneal reshaping uses specially designed rigid gas-permeable contact
      lenses. It is effective in temporarily reducing or eliminating low to moderate
      myopia. This nonsurgical mode of vision correction allows for good unaided vision
      during waking hours. There are reports of young patients experiencing serious
      adverse events, particularly bacterial and Acanthamoeba keratitis while using
      these lenses, although incidence rates are unknown. SUMMARY: Overnight corneal
      reshaping is an alternative to refractive surgery and must continue to be studied
      and monitored to establish its safety.

PMID- 16900035
TI  - Bioptics: where do things stand?
AB  - PURPOSE OF REVIEW: Bioptics treats complex refractive errors by combining
      refractive techniques with different mechanisms of action, usually using an
      intraocular implant (a phakic or pseudophakic intraocular lens) followed by a
      corneal procedure (laser ablation, intrastromal implant). RECENT FINDINGS: In
      myopia and hyperopia, bioptics with phakic intraocular lenses or refractive lens
      exchange and subsequent excimer laser yields improved predictability and
      unchanged safety, compared with sole intraocular lens surgery. Complications are
      related mainly to intraocular lenses. In keratoconus and pellucid marginal
      degeneration, intracorneal rings have been successfully combined with
      phacoemulsification or with phakic intraocular lenses in a limited number of
      eyes. In the author's series, angle-supported phakic intraocular lenses were
      implanted in 12 eyes to correct a mean regression of -8 D after excimer laser
      (reverse bioptics), achieving a mean spherical equivalent of -0.3 D, mean best
      spectacle-corrected visual acuity of 0.7, and mean uncorrected visual acuity of
      0.5, with 83% of eyes within 0.5 D of spherical equivalent. SUMMARY: Bioptics
      improves vision and halos and adds no particular risks to phakic or pseudophakic
      intraocular lens implantation in either myopia or hyperopia. Reverse bioptics,
      with phakic intraocular lenses or refractive lens exchange, can be used to
      correct regressed corneal surgery.

PMID- 16900036
TI  - Post-laser in-situ keratomileusis ectasia: current understanding and future
      directions.
AB  - PURPOSE OF REVIEW: The aim of this article is to review the causes, risk factors,
      management, and future research directions for corneal ectasia after laser in
      situ keratomileusis. RECENT FINDINGS: Complex corneal biomechanical processes
      influence the integrity of the normal and postoperative cornea, and developing an
      understanding of these processes facilitates recognition of risk factors for
      ectasia after laser in-situ keratomileusis. Currently identified risk factors
      include keratoconus, high myopia, low residual stromal bed thickness from
      excessive ablation or thick flap creation, and defined topographic abnormalities
      such as forme fruste keratoconus and pellucid marginal corneal degeneration.
      Ectasia can also rarely occur in patients without currently identifiable risk
      factors, and future identification of at-risk patients may be facilitated by
      corneal interferometry and corneal hysteresis measurements. Utilization of
      intraoperative pachymetry measurements at the time of surgery and confocal
      microscopy prior to enhancement to measure residual stromal bed thickness should
      avoid unanticipated low residual stromal bed thickness. Management options for
      ectasia after laser in situ keratomileusis include intraocular pressure
      reduction, rigid gas permeable contact lenses, and intracorneal ring segments, in
      addition to corneal transplantation. In the future, collagen cross-linking may
      reduce corneal steepening and improve refractive error. SUMMARY: When ectasia
      develops, early recognition and proper management are essential to prevent
      progression, to promote visual rehabilitation, and to reduce the need for corneal
      transplantation for these patients.

PMID- 16900037
TI  - Bibliography. Current world literature. Corneal and external disorders.

PMID- 16900038
TI  - Agreement of a work-capacity assessment with the World Health Organisation
      International Classification of Functioning, Disability and Health pain sets and
      back-to-work predictors.
AB  - The degree of agreement between a clinical multi-professional work-capacity
      assessment and the Comprehensive World Health Organisation International
      Classification of Functioning, Disability and Health (ICF) Core Sets for chronic
      pain and risk factors for no return to work was investigated. A review of data
      records and interviews with team members included measures of body
      function/structure, activities/participation and environmental factors.
      Predictors for return to work were reviewed. The team used eight different
      methods for data collection. Of the 29 categories concerning environmental
      factors, two were excluded; the methods used were more unstructured, e.g.
      interviews. The agreement with the 41 predictors of work resumption was high. The
      clinical work-capacity assessment agreed largely with the Comprehensive ICF Core
      Sets for the components body function, body structure, activities and
      participation. Nine categories out of 69 were not included. The clinical work
      capacity assessment agreed largely with the Comprehensive ICF Core Sets for
      chronic pain conditions and with 40 predictors of work resumption. Clinically
      speaking, however, the current work-capacity assessment lacks on-the-job site
      evaluations and this most certainly affects reliability. The same is true for
      ICF, although the structure lacks proper coding for relevant factors found at
      work.

PMID- 16900039
TI  - Development of the new Family Impact of Assistive Technology Scale.
AB  - Children with physical disabilities generally require more care, attention and
      direct supervision than children without disabilities. Research demonstrates that
      these higher care-giving demands are associated with poorer psychological and
      physical health states for parents and other family members. Assistive
      technologies may have a role in mitigating caregiver stress and burden by
      improving functional performance, social interaction and autonomy in children
      with physical disabilities. In this paper, we report on the initial development
      and testing of the Family Impact of Assistive Technology Scale - a new measure
      designed to detect the multidimensional effect of assistive device use on
      families who have young children with disabilities. To study the content validity
      and face validity of the Family Impact of Assistive Technology Scale, we
      conducted structured evaluations of the proposed constructs and items with 14
      clinical experts and parents of young children with cerebral palsy. Experts
      agreed that the Family Impact of Assistive Technology Scale contains the key
      variables needed to study the effect of assistive technology use on child and
      family functioning. Parents concurred that items on the preliminary version were
      relevant and clear. Further research is planned to estimate the reliability and
      other aspects of validity of the Family Impact of Assistive Technology Scale.

PMID- 16900040
TI  - Adjustment to severe disability: constructing and examining a cognitive and
      occupational performance model.
AB  - Ninety adults with severe physical disabilities were tested with respect to their
      adjustment to severe disabilities in their adapted computerized work environment
      1 year following occupational therapy consultation. The research goal was to
      examine a model that incorporates variables from the cognitive coping model (self
      esteem, appraisal and social support) and variables from the occupational
      performance model (engagement in activities, involvement in work/study, time of
      typing performance and environmental adaptations). Findings showed goodness of
      fit between the observed and the proposed research models, although few changes
      in positions and relations were found. Self-esteem and time of performance were
      found to be core variables connecting cognitive and functional variables. Age and
      activities of daily living were the only background variables that contributed to
      the model. Research and rehabilitation clinical implications are discussed.

PMID- 16900041
TI  - Coping mechanisms of some blind trainees engaging in agricultural rehabilitation
      in a Nigerian training centre for the blind.
AB  - This study was conducted to assess the coping mechanisms of some blind trainees
      engaged in agricultural activities at the Nigeria Training Centre for the Blind,
      Ogbomoso, Oyo State, Nigeria. The participants in this study were blind trainees
      and agricultural inspectors. Focus group discussions were used to elicit their
      feelings concerning their coping mechanisms with agricultural activities at the
      centre. In addition, a practical session, and participatory observation, was
      carried out to examine the trainees and their reactions to the agricultural
      training programmes. Findings revealed that the blind trainees could effectively
      undertake farming activities despite their disability. It was, however, noted
      that the facilities for agricultural training programme in the centre are not
      inadequate. Moreover, the study further discovered that the number of blind
      persons seeking agricultural training was far less than the expected intake for
      the centre. There were also more male than female trainees in the centre. Based
      on the findings, recommendations were made to improve the farming training
      programme for blind trainees at the centre. More facilities should be provided
      and efforts made to encourage more blind persons to use the centre. This will
      discourage begging and dependence, activities often engaged in by blind persons
      who have not been rehabilitated.

PMID- 16900042
TI  - Correlation between generic health status and region-specific functional measures
      on patients with neck pain.
AB  - This is a cross-sectional and prospective study to examine the correlation
      between the Northwick Park Neck Pain Questionnaire and the Medical Outcomes 36
      Item Short-Form Health Survey on patients with neck pain in the course of
      physiotherapy. A total of 359 consecutive adult patients with neck pain, from
      three physiotherapy outpatient departments, who completed the Northwick Park Neck
      Pain Questionnaire and Medical Outcomes 36-Item Short-Form Health Survey, were
      observed and measured at different intervals - at the beginning of physiotherapy,
      at week 3, week 6 and upon discharge from physiotherapy. The results showed that
      both the Northwick Park Neck Pain Questionnaire and the Medical Outcomes 36-Item
      Short-Form Health Survey were able to differentiate patients with neck pain in
      health and diseased states. The Spearman's correlation coefficients between the
      Northwick Park Neck Pain Questionnaire and the 36-Item Short-Form Health Survey
      physical and mental component summary scores at entry of physiotherapy were -0.64
      with the physical component summary score and -0.44 with the mental component
      summary score, and, at discharge from physiotherapy, were -0.75 with the physical
      component summary score and -0.46 with the mental component summary score. The
      Northwick Park Neck Pain Questionnaire has psychometric properties with both
      physical and mental dimensions of measurement of pain in patients with neck pain.

PMID- 16900043
TI  - Internet-based rehabilitation for individuals with chronic pain and burnout: a
      randomized trial.
AB  - This study investigates utilization of the Internet in the rehabilitation of
      people on long-term sick leave with chronic pain and/or burnout. Fifty-five
      people were randomly assigned to two groups: a treatment group (n = 27) that
      participated in a rehabilitation course over the Internet and a waiting list
      group (n = 28). The goals were to improve participants' health and increase
      quality of life, and, for those who were not on permanent disability pensions, to
      increase work capacity, if possible. A 20-week program, based on 19 films on
      different themes, was supplemented with written material and a Socratic dialogue
      over the Internet. Upon completion of the rehabilitation course, statistically
      significant improvements were observed in the treatment group in comparison to
      the waiting list group, for variables such as depression, pain, vitality, social
      function, performance problems involving work or other activities due to physical
      illness and the presence of stress symptoms. Thirteen of 23 individuals (57%)
      also increased their work capacity. The number needed to treat regarding
      recovering from anxiety and depression was 2. For increased work capacity, the
      number needed to treat was 3. Rehabilitation of people on long-term sick leave
      carried out over the Internet is a good complement to other rehabilitation
      programs.

PMID- 16900044
TI  - Return to work among sickness-absent Danish employees: prospective results from
      the Danish Work Environment Cohort Study/National Register on Social Transfer
      Payments.
AB  - This study investigates the determinants within socio-demography, health
      behaviour, employer characteristics, and psychosocial and physical work
      environment for return to work. In 2000, a total of 5357 employees were
      interviewed regarding age, gender, family status, education, health behaviour,
      employer characteristics and work environment. They were followed in a national
      register for 18 months in order to identify subjects with 2 weeks or more of
      sickness absence. They were followed for an additional 12 months in order to
      establish associations between baseline measurements and time to first return to
      work. A total of 930 (17.4%) employees experienced sickness absence in the 18
      months after baseline. During the 12-month follow-up, 856 (92.0%) returned to
      work, the mean absence period being 6.6 weeks. Prolonged time to first return to
      work was associated with female gender, increased age, no post-school education,
      being employed by a public employer, working at a workplace with 20 or more
      employees, high emotional demands in work, high job insecurity and sedentary
      work. There were no associations between health behaviour variables and return to
      work. The study indicates a potential for promoting return to work through
      interventions targeting emotional job demands, job insecurity and decreasing the
      risks associated with sedentary work.

PMID- 16900045
TI  - A pilot study of sensory retraining for the hemiparetic foot post-stroke.
AB  - Sensory training post-stroke has been favourably reported in the literature for
      the hemiparetic upper limb. Little is known, however, of the usefulness of such
      techniques in the lower limb. This is despite the knowledge that accurate sensory
      feedback is vital for adaptability in motor control, particularly during balance
      and weight shift during standing. This pilot study used a single-case, repeated
      measures design, with three subjects with hemisensory loss in their lower limb.
      Pre-intervention and post-intervention measures included light touch and
      proprioception, duration of single-limb stance, sway path length and duration of
      transition from double-to single-limb stance. The intervention involved 2 weeks
      of intensive sensory appreciation training, involving a hierarchy of sensory
      education, experiences and interpretation. Testing post-intervention demonstrated
      statistically significant changes in light touch appreciation for two subjects
      and in some postural control parameters in the third subject. Clinically
      favourable trends were shown in other measures. This initial study shows
      promising results for the incorporation of sensory training in the lower limb
      post-stroke, particularly if consideration is given to motivation, attention and
      functional application.

PMID- 16900046
TI  - The impact evaluation of physical therapy on the quality of life of
      cerebrovascular stroke patients.
AB  - This study aimed to evaluate the impact of physical therapy on the quality of
      life of patients presenting with a motor deficit caused by ischemic stroke at the
      median cerebral artery. Physical therapeutic intervention consisted of three
      sessions per week of conventional kinesiotherapy; 50 min each, for three
      consecutive months. The sample comprised 18 patients aged between 18 and 72 years
      old, evaluated according to the Stroke Impact Scale. There was a significant
      difference for the following domains: strength (P < 0.001), daily life activities
      (P < 0.001), mobility (P = 0.001), manual function (P = 0.004) and social
      participation (P=0.001). We were able to conclude that physical therapy,
      performed for up to three 50-min weekly sessions for 3 consecutive months,
      resulted in the reduction of motor deficits and functional improvement,
      consequently promoting favorable effects on the quality of life of patients
      presenting with motor deficit due to ischemic stroke.

PMID- 16900047
TI  - Adaptation and coping following a first stroke: a qualitative analysis of a
      phenomenological orientation.
AB  - Stroke can have consequences in all areas of a person's life. If not coped with
      optimally, this life event will have a deleterious effect on the quality of life.
      The aim of this study was to improve understanding of appraisal and coping, post
      stroke. Ten individuals were purposely recruited upon admission for a first
      stroke to participate in this qualitative study. Participants were asked to share
      their personal experiences with regard to their efforts to deal with the
      consequences of the stroke. In-depth interviews were transcribed verbatim and the
      content was analyzed using a rigorous method, inspired by a phenomenological
      orientation. Seven themes related to appraisal (unpredictability, overwhelming,
      feeling out of control, threat, turning point, acceptance/resignation and future
      prospects) and five themes related to coping (active and passive compensation,
      escape, change how the situation is perceived and utilization of resources)
      emerged from the content analysis of the in-depth interviews. In conclusion,
      since returning to the previous life style and activities is rather improbable,
      changing how the situation is perceived appears to be the most effective way of
      coping, in order to reach a state of acceptance/resignation favourable to an
      optimal quality of life.

PMID- 16900048
TI  - A novel robot training system designed to supplement upper limb physiotherapy of
      patients with spastic hemiparesis.
AB  - Spasticity is velocity and acceleration dependent, and it is therefore important
      to execute physiotherapeutic exercises at a relatively low and constant velocity.
      This can be more accurately managed by a robot than by a person when such
      exercises are administered continuously for more than 15-20 min. The purpose of
      this project was to construct a robot-mediated system that could support upper
      limb physiotherapy of patients with spastic hemiparesis. The system, unlike any
      known robotic therapeutic system, uses unmodified industrial robots to carry out
      passive physiotherapy on the upper limb (including the movements of the shoulder
      and the elbow). An initial trial was executed in order to assess its safety and
      to gain experience of the robot-mediated therapy. Four healthy subjects and eight
      patients with spastic hemiparesis were included. Each subject received 30-min
      long robotic physiotherapy sessions over 20 consecutive workdays. The 12
      participants received, in total, 240 robot-mediated physiotherapeutic sessions.
      No dangerous situation or considerable technical problem occurred; the robots
      executed the therapy programme as intended. Investigation of the effectiveness of
      this kind of therapy was not an aim of this initial trial; however, the patients'
      clinical status was followed and some favourable changes were found regarding the
      spasticity of elbow flexors and shoulder abductors. According to the experiences
      of the first clinical investigation, the programming interface and the mechanical
      interface device between the patient and the robots had been improved. A
      controlled clinical study is under way to assess the effectiveness of the REHAROB
      movement therapy.

PMID- 16900049
TI  - Ground-foot reaction forces in hemiplegic gait patterns with and without
      orthopaedic aids.
AB  - The objective of this study was to attempt the analysis of the ground-foot
      reaction forces in hemiplegic patients in routine gait re-education conditions,
      with and without supporting this process with typical orthopaedic aids. Ninety
      people with hemiparesis participated. The subjects were divided into three
      groups, according to their locomotion type (no walking aids, stick and elbow
      crutch). The ground-foot reaction forces during level gait trial were measured
      for each subject. Analysis was carried out by means of Kistler lane. The ANOVA
      results showed a considerable effect on almost all ground-foot reaction force
      parameters, brought about both by the paralysis itself and any walking stick or
      elbow crutch supporting locomotion. The use of the orthopaedic provisions,
      especially the elbow crutch, prolongs the time of the single-stance phase
      duration considerably. In conclusion, the distinct asymmetry of hemiplegic gait
      manifests itself in the distribution of the ground-foot reaction force. In the
      sagittal plane, the values of the force impulse indicate that people with a
      walking stick accelerated using the healthy limb and slowed down using the
      paralysed limb. In elbow crutch patients the acceleration function seems to be
      taken over by the crutch.

PMID- 16900050
TI  - Cognitive functions among Hong Kong Chinese people with schizophrenia.
AB  - Persons with schizophrenia show deficits in a variety of cognitive domains
      including executive function, attention, memory and language. Similar interest in
      studying the impact of cognitive deficits on the everyday functioning of people
      with schizophrenia has been documented. This study examined the cognitive
      functioning among Hong Kong Chinese schizophrenic patients compared with other
      patient groups, and its relationship with functional outcome, especially in the
      social aspect. Results indicated that schizophrenic patients presented with mild
      cognitive problems compared with neurosurgical and demented patients. Initial
      support was found in relating cognitive functions, as measured by Neurobehavioral
      Cognitive Status Examination, with functional outcome as measured by Functional
      Independence Measures. The implication for community rehabilitation is also
      discussed.

PMID- 16900051
TI  - Working memory and sentence comprehension of Hong Kong Chinese children with
      specific language impairment.
AB  - Children with Specific Language Impairment present with delayed language
      development, but do not have a history of hearing impairment, mental deficiency,
      or associated social or behavioral problems. Non-word repetition was suggested as
      an index to reflect the capacity of phonological working memory. There is a
      paucity of such studies among Hong Kong Chinese children. This preliminary study
      aimed to examine the relationship between phonological working memory and
      Specific Language Impairment, through the processes of non-word repetition and
      sentence comprehension, of children with Specific Language Impairment and pre
      school children with normal language development. Both groups of children were
      screened by a standardized language test. A list of Cantonese (the commonest
      dialect used in Hong Kong) multisyllabic nonsense utterances and a set of 18
      sentences were developed for this study. t-tests and Pearson correlation were
      used to study the relationship between non-word repetition, working memory and
      specific language impairment. Twenty-three pre-school children with Specific
      Language Impairment (mean age = 68.30 months; SD = 6.90) and another 23 pre
      school children (mean age = 67.30 months; SD = 6.16) participated in the study.
      Significant difference performance was found between the Specific Language
      Impairment group and normal language group in the multisyllabic nonsense
      utterances repetition task and the sentence comprehension task. Length effect was
      noted in Specific Language Impairment group children, which is consistent with
      the findings of other literature. In addition, correlations were also observed
      between the number of nonsense utterances repeated and the number of elements
      comprehended. Cantonese multisyllabic nonsense utterances might be worth further
      developing as a screening tool for the early detection of children with Specific
      Language Impairment.

PMID- 16900052
TI  - How is the collaborative-practice competency operationalized by mental health
      workers?
AB  - The recovery-focused competencies currently endorsed in policy emphasize
      collaborative relationships between mental health workers, service users,
      families and communities. Based on a qualitative research methodology, multi
      disciplined practitioners shared their perceptions as to how mental health
      workers could operationalize collaborative relationships. Two community mental
      health centres were the setting for three focus groups, where 16 voluntary
      participants contributed to focused discussions. Participants discussed the
      pragmatics of how they work collaboratively; identifying knowledge and attitudes
      that underpin their practice, and elaborating on environmental influences that
      impact on a collaborative approach. Findings from the study recommend the
      practitioner role as one of advocacy and facilitation. The collaborative
      approach, which is inextricably related to the quality of the practitioner
      service user relationship, aids sense-making for service users of their mental
      health experience. This requires of practitioners the qualities of openness,
      expression of hope, genuineness and people-first attitude that supports the
      building of knowledge rather than communicating it.

PMID- 16900053
TI  - Achieve optimum success with upfront planning.

PMID- 16900055
TI  - Can we learn a few things from Google?

PMID- 16900056
TI  - Reap value from your vendor.

PMID- 16900057
TI  - Visitation guidelines promote safe, satisfying environments.

PMID- 16900058
TI  - Crack the code of patient falls.

PMID- 16900059
TI  - Who'll replace you when you're gone?

PMID- 16900061
TI  - Making the right choice: strategies for effective interviews.

PMID- 16900062
TI  - New treatment options push patient care forward.

PMID- 16900063
TI  - Hospitalists here to stay.

PMID- 16900065
TI  - Preventing hip fractures in our aging society.

PMID- 16900066
TI  - Traumatic pelvic fractures.
AB  - Pelvic fractures can be a big challenge in caring for the injured patient. Pelvic
      fractures are important as a cause for morbitidy and mortality. The mortality can
      be 30% with unstable pelvic ring injuries, and 10-12% of this percentage alone is
      due to blood loss. Multiple complications can occur during a pelvic fracture.
      This article will help nurses assess and manage patients with pelvic injuries.
      Topics covered in the article include basic anatomy of the pelvis, diagnostic
      tests performed after a pelvic fracture, types of pelvic fractures, management of
      pelvic fractures, and complications.

PMID- 16900068
TI  - Objective measurement of stiffness in knee osteoarthritis.
AB  - PURPOSE: The purpose of this study was to evaluate an objective measure of knee
      joint stiffness in older adults with and without knee osteoarthritis. DESIGN:
      Methodological study of the modified pendulum test. SAMPLE: A convenience sample
      of community-dwelling older adults (n = 41). METHODS: Knee angle oscillation data
      were collected with a VICON motion analysis system and were used to calculate
      stiffness and damping coefficients and measures of joint stiffness. FINDINGS:
      Although some testing problems were encountered early in the study, useable data
      were obtained from 29 participants. Within-participant variability for calculated
      stiffness and damping coefficients was low (0.55% and 8.92%, respectively),
      whereas the between-participant variability was high for both the stiffness
      (99.45%) and damping (91.08%) coefficients. DISCUSSION: The modified pendulum
      test is a reliable method for evaluation of knee joint stiffness. This method can
      be used in collection of outcome data for future intervention studies addressing
      joint stiffness.

PMID- 16900069
TI  - Broken bones: common pediatric fractures--part I.
AB  - Musculoskeletal injuries are one of the most frequently encountered problems in
      pediatric practice, with fractures accounting for a surprisingly large percentage
      of these injuries. A fracture occurs when bone is subjected to more energy than
      it can absorb. Pediatric healthcare providers must have a good understanding of
      normal bone growth and development and must recognize common mechanisms of injury
      and fracture patterns seen in children. Nearly 20% of children who present with
      an injury have a fracture, and it is estimated that 42% of boys and 27% of girls
      will sustain a fracture during childhood (Wilkins, 1996). The immature skeleton
      has several unique properties that directly affect the management of fractures in
      children.

PMID- 16900070
TI  - Multidisciplinary patient education for total joint replacement surgery patients.
AB  - The purpose of this article is to describe a preadmission, preoperative
      educational program offered free of charge for patients undergoing total joint
      replacement surgery at a large teaching hospital located in metropolitan Detroit,
      Michigan. In establishing the preoperative educational program, a
      multidisciplinary approach was used to provide a comprehensive learning
      environment for patients and their families. To evaluate the effectiveness of the
      program, patients completed surveys at the end of each class. Patients reported
      that their expectations of the program were met, they were less anxious about
      their surgery as a result of attending the classes, and the preoperative teaching
      by the multidisciplinary team was effective. Having a live session that offered
      an opportunity to ask individual and specific questions to each healthcare
      professional with immediate feedback proved to be a positive experience for
      patients. Patients' comments supported the multidisciplinary team's impression
      that real-time, interactive teaching was highly valued by patients and their
      caregivers.

PMID- 16900072
TI  - Pain perception and its relation to functional status post total knee
      arthroplasty: a pilot study.
AB  - PURPOSE: This pilot study examined the influence of pain perception on functional
      status. DESIGN: A descriptive longitudinal correlational exploratory design was
      used. SAMPLE: The sample comprised 23 participants ranging in age from 47 to 85
      years. RESULTS: Data were collected for pain perception components, anxiety, and
      functional status. Negative correlations were noted between pain and functional
      status on days 42 and 84. Common descriptors used over the first 3 days were
      sharp, aching, tender, and tiring. CONCLUSIONS: Pain intensity is only one
      component of pain perception. Management of the sensory and affective components
      needs further research.

PMID- 16900073
TI  - Boxer's fracture.
AB  - Boxer's fracture is a common name for a fracture of the distal fifth metacarpal
      and received its name from one of its most common causes, punching an object with
      a closed fist. It can occur from a fistfight or from punching a hard object. The
      injury of a "Boxer's Fracture" earned the name from the way in which the injury
      occurred, punching an immovable object with a closed fist and no boxing mitt
      (Figure 1). Naturally, a "Boxer" usually punches his fist into his opponent's
      face or body. An angry person may perform the same action into a person, or into
      the wall. The third person may be performing a task and strike something with his
      fist with forceful action accidentally. In any event, if the closed fist
      "punches" into an immovable or firm object with force, the most frequent injury
      sustained would be a fracture of the fifth metacarpal neck. Some caregivers would
      also call a fourth metacarpal neck fracture a boxer's fracture.

PMID- 16900075
TI  - The pathogenesis and biomechanics of turf toe.
AB  - Sprain injury to the 1st metatarsophalangeal joint is referred to as turf toe.
      The incidence of this injury has increased over the years secondary to athletic
      fields being covered by artificial turf and also by increased flexibility of the
      toe box in athletic shoes. The pathogenesis of turf toe will be presented in this
      article.

PMID- 16900077
TI  - The elbow: a hinge joint.

PMID- 16900080
TI  - Menopause, insulin resistance, and risk factors for cardiovascular disease.
AB  - OBJECTIVE: In this retrospective analysis of the European Group for the Study of
      Insulin Resistance database, a clamp data pooling project, a cardiovascular risk
      score (CVS) was assessed to verify whether hyperinsulinemia and/or insulin
      resistance were independent cardiovascular risk factors and to investigate how
      menopause affected CVS and insulin resistance. DESIGN: Information was obtained
      on whole-body glucose uptake (M), determined by the euglycemic hyperinsulinemic
      clamp technique, normalized by fat-free mass (FFM), and insulin concentration (I)
      at a steady state. Body composition was estimated using a labeled water technique
      or bioimpedance. Other parameters measured included blood pressure, lipid levels,
      and waist-to-hip ratio. CVS was computed using a structural equation model that
      included age, body mass index, blood lipids, and blood pressure. The study
      population included 523 normal and overweight patients. Women were grouped
      according to fertility status, and men, according to age (cutoff 50 y). RESULTS:
      M/kg(FFM)/I significantly decreased after menopause (12.41 +/- 3.40 vs 10.96 +/-
      3.68; P < 0.01) and in men 50 years and older (11.39 +/- 3.47 vs 10.32 +/- 3.77
      micromol x min(-1) x kg(-1) x microUI/mL; P < 0.02). CVS was lowest in fertile
      women (-0.414 +/- 0.57 vs 0.107 +/- 0.43; P < 0.0001) and highest in men 50 years
      and older (0.045 +/- 0.455 vs 0.257 +/- 0.51; P < 0.001). CVS significantly
      correlated with M/kg(FFM)/I in men 49 years and younger (r(o) = -0.27, P <
      0.0001) and 50 years and older (r(o) = -0.38, P < 0.0001) and with fasting
      insulin in fertile women (r(o) = -0.29, P < 0.01) and in the other groups (r(o)
      ranging from 0.37 to 0.45, P < 0.0001). CONCLUSIONS: Menopause does not seem to
      strictly relate to a decrease in insulin sensitivity as postmenopausal women had
      the same insulin sensitivity as age-matched men. In the population studied, the
      best predictor of CVS was fasting insulin rather than insulin sensitivity.

PMID- 16900081
TI  - Wild berries: a good source of omega-3.
AB  - It has been reported that some wild green vegetables are good sources of alpha
      linolenic acid (ALA, an essential omega-3 fatty acid). Using available data from
      the Norwegian food composition table, the present study shows that three common
      Nordic berries (blueberry, cloudberry and cowberry) on average contain 0.7 g of
      fat (=21% of total energy) and 0.25 g ALA (=36% of total fat) per 100 g, which is
      quite similar to what has been reported for the ALA-rich wild green vegetables.
      In addition, this study shows that a hypothetical replacement of 5% of Norwegian
      8th grade girls' diet, with a similar energy amount of wild berries, would
      significantly improve the diet - also improve intake of nutrients not commonly
      associated with berries.

PMID- 16900082
TI  - A longitudinal study of serum cobalamins and its binding proteins in lactating
      women.
AB  - OBJECTIVE: To examine longitudinal changes in serum cobalamins, transcobalamin
      (TC) and haptocorrin (HC) during lactation and to investigate the influence of
      vitamin B12 supplementation on these parameters. DESIGN: A 9-month follow-up
      study. SUBJECTS AND METHODS: Lactating mothers (N=89) including 23 supplemented
      with vitamin B12 (1-18 microg/daily), 41 partly supplemented and 25 not
      supplemented. Blood samples collected 3 weeks (baseline) and 4 and 9 months post
      partum were analysed for cobalamins, TC and HC. Both the total concentration and
      the cobalamin-saturated form (holo) of TC and HC were analysed. RESULTS: No
      significant differences were observed in serum cobalamins or its binding proteins
      related to supplementation with vitamin B12 or the duration of lactation. Serum
      cobalamins remained unchanged from 3 weeks to 9 months post-partum. Total TC
      (holoTC) (median+/-s.e. pmol/l) decreased between 3 weeks (710+/-23 (85+/-12))
      and 9 months (602+/-21 (76+/-11)) (P<0.0001 (P=0.0002)), whereas total HC
      (holoHC) increased from (422+/-11 (300+/-9)) at 4 months to (455+/-13 (317+/-10))
      to 9 months post-partum (P<0.0001 (P<0.0001)). CONCLUSION: We report a decrease
      in TC and an increase in HC during a 9-month period post-partum. No differences
      were observed between the vitamin B12-supplemented and the unsupplemented groups.
      Thus, supplementation with vitamin B12 has no impact on the circulating level of
      serum cobalamins or its binding proteins in a Danish population of lactating
      mothers.

PMID- 16900083
TI  - Differences in short-term metabolic responses to a lipid load in lean (resistant)
      vs obese (susceptible) young male subjects with habitual high-fat consumption.
AB  - OBJECTIVE: To determine the role of macronutrients oxidation ability in the
      postprandial response to a high lipid load in the mechanisms conferring
      resistance or susceptibility to obesity. SUBJECTS AND DESIGN: Nine lean and nine
      obese young male subjects with habitual similar high-fat intake (>40 % of energy)
      and comparable physical activity were selected and categorized as 'resistant',
      those who remained lean (body mass index (BMI) <25 kg/m2), and 'susceptible',
      those who were obese (BMI>30 kg/m2). Fasting blood samples were taken for the
      evaluation of blood metabolic and hormonal variables. Resting metabolic rate
      (RMR) and substrates oxidation were measured by indirect calorimetry, in the
      fasting state and every 30 min for 3 h after a rich lipid meal (fat 94.7%)
      supplied to cover the 50% of the volunteers energy requirements. The study was
      performed at the Metabolic Unit of the University of Navarra. RESULTS: Fasting
      RMR and lipid oxidation were higher in obese-susceptible subjects. However,
      similar values were found in both groups after adjustment for fat mass and free
      fat mass. The cumulative postprandial fat oxidation was also similar in both
      groups (despite having different tissue metabolic activity), whereas cumulative
      carbohydrate oxidation was lower in the obese-susceptible group. The thermic
      effect of food (% of dietary induced thermogenesis) was lower (P<0.05) in the
      susceptible-obese subjects. The energy and fat balance were more positive in the
      obesity-susceptible individuals after the high fat load, who also showed higher
      fasting homeostatic model assessment index, low-density lipoprotein-cholesterol
      and triacylglyceride levels, hyperleptinemia and hypoadiponectinemia. CONCLUSION:
      Lean-resistant individuals came closer to achieving fat balance than obese
      susceptible subjects. These metabolic and hormonal differences are probably
      genetically determined.

PMID- 16900084
TI  - Basal metabolic rate of Brazilians living in the Southwestern United States.
AB  - Estimation of energy requirements relies on adequate values of basal metabolic
      rate (BMR). Prediction equations recommended for international use have been
      shown to overestimate BMR in populations living in the tropics. We have
      previously shown the inadequacy of these equations in samples of Brazilians
      living in tropical and temperate regions of the country. We sought to investigate
      whether BMR could adequately be estimated by prediction equations in a sample of
      Brazilians living in a different setting: the Sonoran desert of the Southwestern
      USA. BMR was measured under standard conditions in 33 subjects (14 men). Mean
      bias (estimated-measured) varied from 404.4 to 708.6 kJ day(-1) in women and
      566.8 to 1122.8 kJ day(-1) in men, representing 8.5-15 and 8.9-17.6%
      overestimation, respectively, using the Schofield equations. Bland and Altman
      analyses showed large, relevant limits of agreement. The results using the
      recommended equations for the American population (IOM, 2005) were only 2%
      different from the Schofield equations. The Harris and Benedict equations yielded
      higher overestimations (15.0 and 16.8% for women and men, respectively) and the
      Henry and Rees equations also overestimated BMR (8.5 and 8.9%) even though they
      were developed for populations from the tropics, although to a lesser degree. It
      is concluded that the equations currently recommended for international use are
      not appropriate for Brazilians living in the Southwestern USA.

PMID- 16900085
TI  - Diet, serum insulin-like growth factor-I and IGF-binding protein-3 in European
      women.
AB  - OBJECTIVE: The aim of this study was to examine the relationship of diet with
      serum insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 in women.
      DESIGN: Cross-sectional study. SETTING AND SUBJECTS: The population are 2109
      women who were control subjects in a case-control study of breast cancer nested
      in the European Prospective Investigation into Cancer and Nutrition. Control
      subjects were randomly chosen among risk sets consisting of female cohort members
      alive and free of cancer (except non-melanoma skin cancer) at the time of
      diagnosis of the index case. Matching criteria were age at enrolment, follow-up
      time, time of the day of blood collection and study centre. Diet was measured
      through validated questionnaires. Serum hormone concentrations were measured by
      enzyme-linked immunosorbent assays. The relationship between serum IGF-I, IGFBP
      3, and intake of nutrients and foods was explored by linear regression in models
      adjusted for energy intake, age, body mass index, smoking, physical activity,
      centre and laboratory batch. RESULTS: Serum IGF-I levels were positively related
      to protein intake (P(trend)<0.001), but not related to energy, fat or
      carbohydrate intake. Positive relationships were observed with the intake of milk
      (P(trend)=0.007), calcium (P(trend)<0.001), magnesium (P(trend)=0.003),
      phosphorus (P(trend)<0.001), potassium (P(trend)=0.002), vitamin B6
      (P(trend)=0.03), vitamin B2 (P(trend)=0.001) and inverse relationships with
      vegetables (P(trend)=0.02) and beta-carotene (P(trend)=0.02). IGFBP-3 was not
      related with most of the nutrients and foods in this study. CONCLUSIONS: In this
      population, circulating IGF-I is modestly related with the intake of protein and
      minerals, and with milk and cheese, while IGFBP-3 does not appear to be related
      with diet.

PMID- 16900086
TI  - The global diabetes pandemic: the Tunisian experience.
AB  - OBJECTIVE: The prevalence of diabetes mellitus is known to be increasing rapidly
      worldwide, but few population-based surveys have been undertaken in Africa or the
      Middle East. The aims of this study are to report the prevalence of diabetes
      mellitus and impaired fasting glucose (IFG) in Tunisia, to compare the prevalence
      to previous studies and to analyse the relationship between diabetes and age,
      sex, area of residency and body mass index (BMI). SUBJECTS AND SETTING: We have
      used data from the Tunisian National Nutrition Survey, a cross-sectional health
      study providing a large nationally representative sample of the Tunisian
      population including 3729 adults. We used the American Diabetes Association
      diagnostic criteria to determine the prevalence of diabetes mellitus and IFG.
      RESULTS: The overall diabetes prevalence was 9.9% (9.5% in men and 10.1 in women)
      giving age-adjusted prevalence of diabetes of 8.5% (7.3% in men and 9.6% in
      women). Step-wise logistic regression showed age of more than 40 years, urban
      residency and high BMI to each be significantly and independently related to
      diabetes prevalence. The prevalence of diabetes mellitus has more than doubled in
      Tunisia over a 15-year period. CONCLUSIONS: Our study has demonstrated a high
      prevalence of diabetes in the adult population with a wide difference among the
      rural and urban areas with an increased prevalence compared to previous studies.
      The results underline the need to increase public awareness and to emphasize the
      benefit of lifestyle modification in order to prevent type II diabetes.

PMID- 16900087
TI  - Nephronophthisis type 1 deletion syndrome with neurological symptoms: prevalence
      and significance of the association.
AB  - Type 1 nephronophthisis (NPHP) with homozygous deletions of nephrocystin [NPHP1,
      DEL] has been considered a pure renal disorder, but co-occurrence of extrarenal
      symptoms, mainly retinitis pigmentosa, is observed in a subset of patients.
      Recently, [NPHP1, DEL] has been detected in three patients with Joubert syndrome
      related disorders (JSRDs), who associated neurological signs with a peculiar
      neuroradiological malformation known as the 'molar tooth sign' (MTS). To define
      the frequency of JSRD spectrum in NPHP1 patients, we re-examined 56 cases with
      [NPHP1, DEL] and found an overall incidence of 8.9% (five out 56 patients). All
      had small hyperechoic kidneys and had developed advanced renal failure within 15
      years. Two patients presented the complete features of JSRD with cerebello-renal
      retinal association and MTS. Two others showed, instead, severe intentional
      tremor and thick superior cerebellar peduncles on brain magnetic resonance
      imaging (MRI), and one of them had associated retinopathy. The fifth patient
      presented with hypotonia, developmental delay, central deafness, and ataxia
      associated with Leber congenital amaurosis and liver fibrosis but with normal
      brain MRI. Marked intrafamilial variability of associated extrarenal symptoms was
      observed in familial cases. Deletion extension did not differ in patients with
      isolated renal phenotype and in those with associated neurological symptoms. In
      conclusion, neurological defects varying from subtle involvement of cerebellum
      with thickened peduncle to both JSRD and diffuse central hypotonia are frequent
      in [NPHP1, DEL] patients. Prevalence of such association may justify systematic
      neurological and neuroradiological evaluation.

PMID- 16900088
TI  - Cis and trans regulatory elements in NPHS2 promoter: implications in proteinuria
      and progression of renal diseases.
AB  - Podocin (NPHS2) expression in podocytes is associated with variable degrees of
      proteinuria and progression to renal failure in different glomerular diseases
      that suggests different expression profiles in NPHS2 promoter. Three functional
      polymorphisms in NPHS2 promoter (-51T, -116T, and -535 insCTTTTTT(3)) were found
      determining strong downregulation (-73, -59, and -82%, respectively) of the
      reporter gene expression when transfected in podocytes. Electrophoretic mobility
      shift assay experiments showed that all wild-type variants (-51G, -116C, and -535
      insCTTTTTT(2)) formed specific DNA-protein complexes with podocyte nuclear
      extracts that were abolished by the presence of the rare forms (-51T, -116T, and 
      535 insCTTTTTT(3)). In the case of -51G, upstream stimulatory factor-1 (USF1) was
      identified as the specific trans element in accord to binding inhibition
      experiments and USF1 RNAi silencing. Haplotype analysis of 204 normal controls
      and 545 patients with renal diseases (308 immunoglobulin (Ig)A nephropathy and
      237 focal segmental glomerulosclerosis) evidenced that -116/-51 and -535/P2OL
      formed two blocks in strong linkage disequilibrium in both normal and
      pathological cohorts. The high NPHS2 promoter profile -116C/-51G haplotype was
      more frequent in patients with IgA nephropathy (P-value=0.005) and was associated
      with a better clinical outcome in terms of proteinuria and creatinine levels.
      Overall our study describes functional variants of NPHS2 promoter and
      characterizes trans-acting elements that modulate podocin expression in the
      kidney. High producer NPHS2 promoter haplotypes seem protective in patients with
      chronic glomerular diseases.

PMID- 16900089
TI  - Characterization of hyaluronan cable structure and function in renal proximal
      tubular epithelial cells.
AB  - Alteration in the glycosaminoglycan hyaluronan (HA) has been demonstrated in
      numerous renal diseases. We have demonstrated that renal proximal tubular
      epithelial cells (PTCs) surround themselves in vitro with HA in an organized
      pericellular matrix or 'coat', which is associated with cell migration, and also
      form pericellular HA cable-like structures which modulate PTC-mononuclear
      leukocytes interactions. The aim of this study was to characterize potential
      regulatory mechanism in the assembly of PTC-HA into pericellular cables. HA
      cables are generated by PTCs in the absence of serum. Immunohistochemical
      analysis demonstrates the incorporation of components of the inter-alpha
      inhibitor (IalphaI) family of proteins and versican into HA cables. Addition of
      an antibody to IalphaI/PalphaI (pre-alpha-inhibitor) inhibits cable formation. In
      contrast, inhibition of tumor necrosis factor-alpha-stimulated gene 6 (TSG-6) has
      no effect on cable formation, suggesting that their generation is independent of
      the known heavy-chain transfer activity of TSG-6. Overexpression of HAS3 is
      associated with induction of HA cable formation, and also increased incorporation
      of HA into pericellular coats. Functionally, this resulted in enhanced HA
      dependent monocyte binding and cell migration, respectively. Cell surface
      expression of CD44 and trypsin-released cell-associated HA were increased in HAS3
      overexpressing cells. In addition, hyaluronidase (hyal1 and hyal2) and bikunin
      mRNA expression were increased, whereas PalphaI HC3 mRNA expression was unchanged
      in the transfected cells. The data demonstrate the importance of IalphaI/PalphaI
      in cable formation and suggest that expression of HAS3 may be critical for HA
      cable assembly.

PMID- 16900090
TI  - Glomerular expression of neuronal activity-regulated pentraxin precedes the
      development of anti-Thy-1-induced progressive glomerulosclerosis.
AB  - Although it is clear that genetic predispositions play a role in progressive
      glomerulosclerosis, identification of specific genes is difficult because of
      natural genetic heterogeneity among individuals. We have reported a differential
      susceptibility to progressive glomerulosclerosis after induction of experimental
      glomerulonephritis anti-Thy-1 nephritis in Lewis rat substrains. Glomerular
      lesions in Lewis/Mollegard rats resolve spontaneously, whereas Lewis/Maastricht
      (Lew/Maa) rats develop progressive glomerulosclerosis. This predisposition for
      progressive glomerulosclerosis is governed by unknown genes that are expressed by
      renal cells. Here, differential gene expression analysis using a rat
      complementary DNA micro array revealed neuronal activity-regulated pentraxin
      (Narp) as a candidate gene involved in the remodeling or progression of damaged
      glomeruli. Glomerular Narp mRNA expression was monitored during disease in both
      Lewis sub strains. Immunohistochemistry revealed that Narp protein is exclusively
      expressed in Lew/Maa glomeruli 7 and 14 days after induction of anti-Thy-1
      nephritis. Double-immunofluorescent staining showed that proliferating mesangial
      cells and parietal epithelial cells (PECs) at sites of adhesion to podocytes are
      partially Narp-positive, whereas podocytes fail to express Narp.
      Immunohistochemistry in nephritic Wistar, unilaterally nephrectomized Wistar and
      Sprague-Dawley rats showed that Narp protein is present only in strains that
      develop progressive glomerulosclerosis but never in strains that show remodeling.
      We conclude that Narp is a predictor for anti-Thy-1 nephritis-induced
      glomerulosclerosis and its expression by PECs may be involved in the progression
      to glomerulosclerosis.

PMID- 16900091
TI  - A molecular microbial ecology approach to studying hemodialysis water and fluid.
AB  - Bacteria, or bacteria-derived products, might be responsible for deleterious
      effects in hemodialysis patients. Most microorganisms in hemodialysis water,
      including potential pathogens, are difficult to isolate and might subsist in a
      'viable but not culturable' state or may need specific culture media. A molecular
      culture-independent approach based on the analysis of the 16S rDNA obtained from
      total DNA has been used to better know the diversity of bacteria inhabiting
      hemodialysis water and fluid, and to address the possible health effects
      associated with their presence. Four clone libraries from 16S rDNA (274 clones)
      were analyzed to characterize the species or groups of bacteria present, to
      assess their distribution in the water circuit, and to compare the results with
      those previously obtained in culture-dependent analysis. One hundred and ninety
      seven clones of four gene libraries were analyzed by sequencing, and were
      identified phylogenetically. Clones affiliated to the Alphaproteobacteria group
      led the diversity. The presence in several samples of Alpha-4-proteobacteria,
      recognized as sphingolipids producers, was to be noted. The most abundant clones
      were affiliated to the Betaproteobacteria branch, closely related to the genus
      Herbaspirillum. As known, Alphaproteobacteria and Betaproteobacteria genomes
      might present a manifest excess in CpG sequences and most of them show a
      lipopolysaccharide-rich outer membrane, both described as inducers of innate
      immunity responses. Another abundant group, belonging to the Cyanobacteria class,
      a possible source of cyanotoxins, was not related to any previously cultured
      bacterium. Possible risk implications for hemodialysis patients of the bacterial
      community detected are discussed.

PMID- 16900092
TI  - Satisfaction with care in peritoneal dialysis patients.
AB  - Patient satisfaction is an important aspect of dialysis care, only recently
      evaluated in clinical studies. We developed a tool to assess peritoneal dialysis
      (PD) customer satisfaction, and sought to evaluate and validate the Customer
      Satisfaction Questionnaire (CSQ), quantifying PD patient satisfaction. The CSQ
      included questions regarding administrative issues, Delivery Service, PD
      Training, Handling Requests, and transportation. The study was performed using
      interviews in all Hungarian Fresenius Medical Care dialysis centers offering PD.
      CSQ results were compared with psychosocial measures to identify if patient
      satisfaction was associated with perception of social support and illness burden,
      or depression. We assessed CSQ internal consistency and validity. Factor analysis
      explored potential underlying dimensions of the CSQ. One hundred and thirty-three
      patients treated with PD for end-stage renal disease for more than 3 months were
      interviewed. The CSQ had high internal consistency. There was high patient
      satisfaction with customer service. PD patient satisfaction scores correlated
      with quality of life (QOL) and social support measures, but not with medical or
      demographic factors, or depressive affect. The CSQ is a reliable tool to assess
      PD customer satisfaction. PD patient satisfaction is associated with perception
      of QOL. Efforts to improve customer satisfaction may improve PD patients'
      quantity as well as QOL.

PMID- 16900093
TI  - ADAM19 expression in human nephrogenesis and renal disease: associations with
      clinical and structural deterioration.
AB  - ADAM19, an enzyme from the ADAM (a disintegrin and metalloproteinase) family, is
      involved in various cell-cell and cell-matrix interactions. It can cleave
      epidermal growth factor (EGF)-like growth factors, such as heparin-binding (HB)
      EGF and neuregulin (NRG), from the cell membrane. ADAM-mediated EGF receptor
      activation is crucial in the development of renal pathology. Based on these data,
      we studied ADAM19 in human nephrogenesis and renal disease. We collected 20 fetal
      kidneys and 56 biopsies from patients with various renal diseases. The unaffected
      part of kidneys from eight patients with renal cell carcinoma served as control.
      RNA in situ hybridization revealed widespread ADAM19 mRNA expression in the
      nephrogenic zone of human fetal kidneys. Normal human kidneys showed constitutive
      ADAM19 expression in distal tubules and endothelial cells, whereas proximal
      tubules were negative. In renal disease, ADAM19 was de novo expressed in proximal
      tubules and glomerular mesangium and upregulated in distal tubules and
      endothelial cells. ADAM19 colocalized with tubular and interstitial NRG, however,
      not with HB-EGF. Independent of renal disorder, mesangial ADAM19 expression was
      associated with glomerular damage as assessed by mesangial matrix expansion,
      focal glomerulosclerosis, and glomerular macrophage influx (all P<0.001). ADAM19
      in proximal tubules and in peritubular capillaries was associated with
      interstitial fibrosis (P<0.05). Finally, increasing tubular ADAM19 was associated
      with declining renal function (P<0.05). The abundant ADAM19 expression during
      nephrogenesis points to a role in growth promotion and regulation. The high
      ADAM19 expression in renal disease suggests involvement in profibrotic and
      proinflammatory processes leading to renal deterioration.

PMID- 16900094
TI  - Upregulation of group IB secreted phospholipase A(2) and its M-type receptor in
      rat ANTI-THY-1 glomerulonephritis.
AB  - Treatment of rat glomerular mesangial cell (GMC) cultures with pancreatic
      secreted phospholipase A(2) (sPLA(2)-IB) results in an enhanced expression of
      sPLA(2)-IIA and COX-2, possibly via binding to its specific M-type sPLA(2)
      receptor. In the current study, we have investigated the expression and
      regulation of sPLA(2)-IB and its receptor during glomerulonephritis (GN). In vivo
      we used the well-established rat model of anti-Thy 1.1 GN (anti-Thy 1.1-GN) to
      study the expression of sPLA(2)-IB and the M-type sPLA(2) receptor by
      immunohistochemistry. In addition, in vitro we determined the interkeukin (IL)
      1beta-regulated mRNA and protein expression in primary rat glomerular mesangial
      and endothelial cells as well as in rat peripheral blood leukocytes (PBLs).
      Shortly after induction of anti-Thy 1.1-GN, sPLA(2)-IB expression was markedly
      upregulated in the kidney at 6-24 h. Within glomeruli, the strongest sPLA(2)-IB
      protein expression was detected on infiltrated granulocytes and monocytes.
      However, at the same time, the M-type receptor was also markedly upregulated on
      resident glomerular cells. In vitro, the most prominent cytokine-stimulated
      secretion of sPLA(2)-IB was observed in monocytes isolated from rat PBLs.
      Treating glomerular endothelial cells (GECs) with cytokines elicited only weak
      sPLA(2)-IB expression, but treatment of these cells with exogenous sPLA(2)-IB
      resulted in a marked expression of the endogenous sPLA(2)-IB. Mesangial cells did
      not express sPLA(2)-IB at all. The M-type sPLA(2) receptor protein was markedly
      upregulated on cytokine-stimulated mesangial and endothelial cells as well as on
      lymphocytes and granulocytes. During anti-Thy 1.1 rat GN, sPLA(2)-IB and the M
      type sPLA(2) receptor are induced as primary downstream genes stimulated by
      inflammatory cytokines. Subsequently, both sPLA(2)-IB and the M-type sPLA(2)
      receptor are involved in the autocrine and paracrine amplification of the
      inflammatory process in different resident and infiltrating cells.

PMID- 16900095
TI  - A protective role for programmed death 1 in progression of murine adriamycin
      nephropathy.
AB  - Programmed death 1 (PD-1) is a novel member of the CD28/cytotoxic T-lymphocyte
      associated protein-4 superfamily, which plays an important role in the regulation
      of activated T cells. However, it is not clear how PD-1 is expressed in normal
      and diseased kidney, nor if it has a role in progression of chronic renal
      disease. PD-1 expression and the effect of monoclonal anti-PD-1 antibody (Ab)
      were examined in murine adriamycin nephropathy (AN). BALB/c mice were divided
      into three groups: (a) normal mice, (b) adriamycin (ADR) with control
      immunoglobulin (Ig)G (ADR-IgG), and (c) ADR with anti-PD-1 Ab (ADR-Ab). AN was
      induced by a single intravenous injection of ADR. Anti-PD-1 Ab was given by
      intraperitoneal injection on alternate days from day 0 to day 10, or to day 18.
      Animals were killed at week 4. Renal function, histological change, and cytokine
      expression were examined. PD-1 mRNA was detected in kidney tissue of mice with AN
      in a dose- and time-dependent manner. PD-1 was mainly expressed on injured tubule
      cells and some interstitial cells, which co-stained with alpha-smooth muscle
      actin in AN, but not in normal kidney. Anti-PD-1 treatment up to day 18, but not
      to day 10, worsened glomerular and tubulointerstitial injury. The ratio of
      urinary protein/creatinine was significantly higher in ADR-Ab mice than ADR-IgG
      mice. The number of macrophages was significantly increased in ADR-Ab mice
      compared with ADR-IgG mice. Blockade of PD-1 worsened progressive renal
      histopathological and functional injury in murine AN. This suggests a possible
      protective role for PD-1 in chronic renal disease, and its potential as a
      treatment to slow disease progression.

PMID- 16900098
TI  - Visualizing polynucleotide polymerase machines at work.
AB  - The structures of T7 RNA polymerase (T7 RNAP) captured in the initiation and
      elongation phases of transcription, that of phi29 DNA polymerase bound to a
      primer protein and those of the multisubunit RNAPs bound to initiating factors
      provide insights into how these proteins can initiate RNA synthesis and
      synthesize 6-10 nucleotides while remaining bound to the site of initiation.
      Structural insight into the translocation of the product transcript and the
      separation of the downstream duplex DNA is provided by the structures of the four
      states of nucleotide incorporation. Single molecule and biochemical studies show
      a distribution of primer terminus positions that is altered by the binding of NTP
      and PP(i) ligands. This article reviews the insights that imaging the structure
      of polynucleotide polymerases at different steps of the polymerization reaction
      has provided on the mechanisms of the polymerization reaction. Movies are shown
      that allow the direct visualization of the conformational changes that the
      polymerases undergo during the different steps of polymerization.

PMID- 16900097
TI  - Dynamics in the plasma membrane: how to combine fluidity and order.
AB  - Cell membranes are fascinating supramolecular aggregates that not only form a
      barrier between compartments but also harbor many chemical reactions essential to
      the existence and functioning of a cell. Here, it is proposed to review the
      molecular dynamics and mosaic organization of the plasma membrane, which are
      thought to have important functional implications. We will first summarize the
      basic concepts of Brownian diffusion and lipid domain formation in model
      membranes and then track the development of ideas and tools in this field,
      outlining key results obtained on the dynamic processes at work in membrane
      structure and assembly. We will focus in particular on findings made using
      fluorescent labeling and imaging procedures to record these dynamic processes. We
      will also discuss a few examples showing the impact of lateral diffusion on cell
      signal transduction, and outline some future methodological challenges which must
      be met before we can answer some of the questions arising in this field of
      research.

PMID- 16900099
TI  - Gene expression within a dynamic nuclear landscape.
AB  - Molecular imaging in living cells or organisms now allows us to observe
      macromolecular assemblies with a time resolution sufficient to address cause-and
      effect relationships on specific molecules. These emerging technologies have
      gained much interest from the scientific community since they have been able to
      reveal novel concepts in cell biology, thereby changing our vision of the cell.
      One main paradigm is that cells stochastically vary, thus implying that
      population analysis may be misleading. In fact, cells should be analyzed within
      time-resolved single-cell experiments rather than being compared to other cells
      within a population. Technological imaging developments as well as the stochastic
      events present in gene expression have been reviewed. Here, we discuss how the
      structural organization of the nucleus is revealed using noninvasive single-cell
      approaches, which ultimately lead to the resolution required for the analysis of
      highly controlled molecular processes taking place within live cells. We also
      describe the efforts being made towards physiological approaches within the
      context of living organisms.

PMID- 16900101
TI  - Nutrient regulates Tor1 nuclear localization and association with rDNA promoter.
AB  - TOR is the target of the immunosuppressant rapamycin and a key regulator of cell
      growth. It modulates diverse cellular processes in the cytoplasm and nucleus,
      including the expression of amino acid transporters, ribosomal RNAs and ribosomal
      proteins. Despite considerable recent progress, little is known about the spatial
      and temporal regulation of TOR signalling, particularly that leading into the
      nucleus. Here we show that Tor1 is dynamically distributed in the cytoplasm and
      nucleus in yeast. Tor1 nuclear localization is nutrient dependent and rapamycin
      sensitive: starvation or treatment with rapamycin causes Tor1 to exit from the
      nucleus. Tor1 nuclear localization is critical for 35S rRNA synthesis, but not
      for the expression of amino acid transporters and ribosomal protein genes. We
      show further that Tor1 is associated with 35S ribosomal DNA (rDNA) promoter
      chromatin in a rapamycin- and starvation-sensitive manner; this association is
      necessary for 35S rRNA synthesis and cell growth. These results indicate that the
      spatial regulation of TOR complex 1 (TORC1) might be involved in differential
      control of its target genes. TOR is known as a classic cytoplasmic kinase that
      mediates the cytoplasm-to-nucleus signalling by controlling the localization of
      transcription factors. Our data indicate that TOR might be more intimately
      involved in gene regulation than previously thought.

PMID- 16900102
TI  - The emergence of geometric order in proliferating metazoan epithelia.
AB  - The predominantly hexagonal cell pattern of simple epithelia was noted in the
      earliest microscopic analyses of animal tissues, a topology commonly thought to
      reflect cell sorting into optimally packed honeycomb arrays. Here we use a
      discrete Markov model validated by time-lapse microscopy and clonal analysis to
      demonstrate that the distribution of polygonal cell types in epithelia is not a
      result of cell packing, but rather a direct mathematical consequence of cell
      proliferation. On the basis of in vivo analysis of mitotic cell junction dynamics
      in Drosophila imaginal discs, we mathematically predict the convergence of
      epithelial topology to a fixed equilibrium distribution of cellular polygons.
      This distribution is empirically confirmed in tissue samples from vertebrate,
      arthropod and cnidarian organisms, suggesting that a similar proliferation
      dependent cell pattern underlies pattern formation and morphogenesis throughout
      the metazoa.

PMID- 16900100
TI  - Imaging of cell migration.
AB  - Cell migration is an essential process during many phases of development and
      adult life. Cells can either migrate as individuals or move in the context of
      tissues. Movement is controlled by internal and external signals, which activate
      complex signal transduction cascades resulting in highly dynamic and localised
      remodelling of the cytoskeleton, cell-cell and cell-substrate interactions. To
      understand these processes, it will be necessary to identify the critical
      structural cytoskeletal components, their spatio-temporal dynamics as well as
      those of the signalling pathways that control them. Imaging plays an increasingly
      important and powerful role in the analysis of these spatio-temporal dynamics. We
      will highlight a variety of imaging techniques and their use in the investigation
      of various aspects of cell motility, and illustrate their role in the
      characterisation of chemotaxis in Dictyostelium and cell movement during
      gastrulation in chick embryos in more detail.

PMID- 16900103
TI  - Sumoylated RGS-Rz proteins act as scaffolds for Mu-opioid receptors and G-protein
      complexes in mouse brain.
AB  - The RGSZ1 and RGSZ2 proteins, members of the RGS-Rz subfamily of GTPase
      activating proteins (GAP), are involved in Mu-opioid receptor desensitization.
      The expression of these proteins, as well as of their main target the Gz protein,
      is virtually restricted to the nervous tissue. In synaptosomal membranes, these
      Rz proteins undergo post-translational modifications such as glycosylation and
      phosphorylation, and they may covalently attach to small ubiquitin-like modifier
      (SUMO) proteins. While RGSZ1 exists in conjugated and non-conjugated forms, RGSZ2
      is mostly conjugated to SUMO-1, SUMO-2 and SUMO-3 proteins. These sumoylated
      forms of the GAPs readily associated with Mu-opioid receptors but they associated
      only poorly with Delta receptors. Furthermore, G alpha i2 and G alpha z subunits
      co-precipitated with the sumoylated forms of RGSZ1/Z2 proteins, but to a lesser
      extent with the Ser phosphorylated SUMO-free form of RGSZ1. Upon Mu-opioid
      receptor activation, there is a strong increase in the association of G alpha
      proteins with RGSZ2 proteins that persists for intervals longer than 24 h. This
      effect probably accounts for their role in Mu-opioid receptor desensitization.
      Only a moderate increase was observed with RGSZ1, the non-sumoylated form of
      which probably acts as an efficient GAP for these G alpha subunits. Therefore,
      sumoylation regulates the biological activity of RGS-Rz proteins and it is likely
      that it serves to switch their behavior, from that of a GAP for activated G alpha
      subunits to that of a scaffold protein for specific signaling proteins.

PMID- 16900104
TI  - Chronic fluoxetine treatment increases the expression of PSA-NCAM in the medial
      prefrontal cortex.
AB  - Recent hypotheses suggest that changes in neuronal structure and connectivity may
      underlie the etiology of depression. The medial prefrontal cortex (mPFC) is
      affected by depression and shows neuronal remodeling during adulthood. This
      plasticity may be mediated by the polysialylated form of the neural cell adhesion
      molecule (PSA-NCAM), which is intensely expressed in the adult mPFC. As the
      expression of PSA-NCAM is increased by serotonin in other cerebral regions,
      antidepressants acting on serotonin reuptake may influence PSA-NCAM expression
      and thus counteract the effects of depression by modulating neuronal structural
      plasticity. Using immunohistochemistry, we have studied the relationship between
      serotoninergic fibers and PSA-NCAM expressing neurons in the adult rat mPFC and
      the expression of serotonin receptors in these cells. The effects of fluoxetine
      treatment for 14 days on mPFC PSA-NCAM expression have also been analyzed.
      Although serotoninergic fibers usually do not contact PSA-NCAM immunoreactive
      neurons, most of these cells express 5-HT3 receptors. In general, chronic
      fluoxetine treatment induces significant increases in the number of PSA-NCAM
      immunoreactive neurons and in neuropil immunostaining and coadministration of the
      5-HT3 antagonist ondansetron blocks the effects of fluoxetine on PSA-NCAM
      expression. These results indicate that fluoxetine, acting through 5-HT3
      receptors, can modulate PSA-NCAM expression in the mPFC. This modulation may
      mediate the structural plasticity of this cortical region and opens new
      perspectives on the study of the molecular bases of depression.

PMID- 16900105
TI  - The impact of tryptophan depletion and 5-HTTLPR genotype on passive avoidance and
      response reversal instrumental learning tasks.
AB  - Transient reductions in serotonin levels during tryptophan depletion (TD) are
      thought to impair reward processing in healthy volunteers, while another facet of
      the serotonergic system, the serotonin transporter (5-HTTLPR) short allele
      polymorphism, is implicated in augmented processing of aversive stimuli. We
      examined the impact and interactions of TD and the serotonin promoter
      polymorphism genotype on reward and punishment via two forms of instrumental
      learning: passive avoidance and response reversal. In this study, healthy
      volunteers (n=35) underwent rapid TD or control procedures and genotyping (n=26)
      of the 5-HTTLPR for long and short allele variants. In the passive avoidance
      task, tryptophan-depleted volunteers failed to respond sufficiently to rewarded
      stimuli compared to the control group. Additionally, long allele homozygous
      individuals (n=11) were slower to learn to avoid punished stimuli compared to
      short allele carriers (n=15). TD alone did not produce measurable deficits in
      probabilistic response reversal errors. However, a significant drug group by
      genotype interaction was found indicating that in comparison to short allele
      carriers, tryptophan-depleted individuals homozygous for the long allele failed
      to appropriately use punishment information to guide responding. These findings
      extend prior reports of impaired reward processing in TD to include instrumental
      learning. Furthermore, they demonstrate behavioral differences in responses to
      punishing stimuli between long allele homozygotes and short allele carriers when
      serotonin levels are acutely reduced.

PMID- 16900106
TI  - D1 and D2 receptor antagonist injections in the prefrontal cortex selectively
      impair spatial learning in mice.
AB  - The prefrontal cortex (PFC) is a cortical area involved in selecting and
      retaining information to produce complex behaviors. Within the PFC, the
      dopaminergic system plays an important role in information processing. Thus, the
      objective of this study was to test whether bilateral administration of the D1
      and D2 receptor antagonists in the prelimbic region of the PFC influenced the
      performance of mice in a non-associative spatial learning task. CD1 mice were
      bilaterally microinjected in the PFC with either the D1 receptor antagonist,
      SCH23390 (SCH 6.25; 12.5; 50 ng), or the D2 receptor antagonist, sulpiride (SULP
      12.5; 50; 100 ng) and placed into an open field containing five different
      objects. After three sessions of habituation two objects were repositioned
      (spatial change) and in the subsequent session one of the objects was substituted
      (non-spatial change). No significant alteration was observed in the habituation
      pattern of the animals after D1 or D2 receptor blockade. When two of the objects
      were displaced, control mice explored the displaced objects far more than the non
      displaced ones, while mice treated with SCH or SULP spent a comparable amount of
      time re-exploring the two object categories. Conversely, DA antagonists had no
      effects on the discrimination of the new object. Thus, the administration of both
      SCH and SULP selectively impaired the ability of mice to discriminate a spatial
      change, without affecting any other behavioral parameter. These findings could
      provide a model to study the role of the PFC dopaminergic system in spatial
      learning and to study the neural mechanisms underlying cognitive and attention
      deficits often observed in psychiatric disorders.

PMID- 16900107
TI  - Lost in validation.

PMID- 16900108
TI  - Not for the chicken-hearted.

PMID- 16900109
TI  - Bundling next-generation cancer therapies for synergy.

PMID- 16900110
TI  - A reprise for collaborative financing in biotech.

PMID- 16900111
TI  - Tysabri back on market.

PMID- 16900112
TI  - Alfimeprase to succeed Genentech's alteplase?

PMID- 16900113
TI  - Belated approval of first recombinant protein from animal.

PMID- 16900115
TI  - Profile: Una Ryan.

PMID- 16900116
TI  - Biotech financing retrenches in Q2.

PMID- 16900117
TI  - Diagnostics investors think positive.

PMID- 16900118
TI  - Looking for solid ground along the Critical Path.

PMID- 16900119
TI  - Genetic profiteering.

PMID- 16900120
TI  - Moving diagnostics from the bench to the bedside.

PMID- 16900121
TI  - Should we make a fuss?

PMID- 16900122
TI  - Should we make a fuss?

PMID- 16900125
TI  - Protein annotation by EBIMed.

PMID- 16900123
TI  - Export signals.

PMID- 16900126
TI  - Cancer biomarkers: a systems approach.

PMID- 16900127
TI  - Translating in vivo diagnostics into clinical reality.

PMID- 16900129
TI  - Three barriers to innovative diagnostics.

PMID- 16900130
TI  - Partnering for better microbial diagnostics.

PMID- 16900128
TI  - What brown cannot do for you.

PMID- 16900131
TI  - A change in the market--investing in diagnostics.

PMID- 16900132
TI  - A regulatory perspective on in vitro diagnostics.

PMID- 16900133
TI  - Any diamonds in the diagnostic coal?

PMID- 16900134
TI  - New-wave diagnostics.

PMID- 16900135
TI  - Emerging patent issues in genomic diagnostics.

PMID- 16900136
TI  - Shifting emphasis from pharmacogenomics to theragnostics.

PMID- 16900137
TI  - Recent patent applications in molecular diagnostics.

PMID- 16900138
TI  - AAV hits the genomic bull's-eye.

PMID- 16900139
TI  - All in the RNA family.

PMID- 16900140
TI  - Blueprint of an oil-eating bacterium.

PMID- 16900141
TI  - Specificity by design.

PMID- 16900142
TI  - Transgenesis sunny-side up.

PMID- 16900144
TI  - How does DNA sequence motif discovery work?

PMID- 16900145
TI  - High-resolution computational models of genome binding events.
AB  - Direct physical information that describes where transcription factors,
      nucleosomes, modified histones, RNA polymerase II and other key proteins interact
      with the genome provides an invaluable mechanistic foundation for understanding
      complex programs of gene regulation. We present a method, joint binding
      deconvolution (JBD), which uses additional easily obtainable experimental data
      about chromatin immunoprecipitation (ChIP) to improve the spatial resolution of
      the transcription factor binding locations inferred from ChIP followed by DNA
      microarray hybridization (ChIP-Chip) data. Based on this probabilistic model of
      binding data, we further pursue improved spatial resolution by using sequence
      information. We produce positional priors that link ChIP-Chip data to sequence
      data by guiding motif discovery to inferred protein-DNA binding sites. We present
      results on the yeast transcription factors Gcn4 and Mig2 to demonstrate JBD's
      spatial resolution capabilities and show that positional priors allow
      computational discovery of the Mig2 motif when a standard approach fails.

PMID- 16900146
TI  - Protein biomarker discovery and validation: the long and uncertain path to
      clinical utility.
AB  - Better biomarkers are urgently needed to improve diagnosis, guide molecularly
      targeted therapy and monitor activity and therapeutic response across a wide
      spectrum of disease. Proteomics methods based on mass spectrometry hold special
      promise for the discovery of novel biomarkers that might form the foundation for
      new clinical blood tests, but to date their contribution to the diagnostic
      armamentarium has been disappointing. This is due in part to the lack of a
      coherent pipeline connecting marker discovery with well-established methods for
      validation. Advances in methods and technology now enable construction of a
      comprehensive biomarker pipeline from six essential process components: candidate
      discovery, qualification, verification, research assay optimization, biomarker
      validation and commercialization. Better understanding of the overall process of
      biomarker discovery and validation and of the challenges and strategies inherent
      in each phase should improve experimental study design, in turn increasing the
      efficiency of biomarker development and facilitating the delivery and deployment
      of novel clinical tests.

PMID- 16900147
TI  - The role of companion diagnostics in the development and use of mutation-targeted
      cancer therapies.
AB  - Among all the known differences between cancer and normal cells, it is only the
      genetic differences that unequivocally distinguish the former from the latter. It
      is therefore not surprising that recent therapeutic advances are based on agents
      that specifically target the products of the genes that are mutated in cancer
      cells. The ability to identify the patients most likely to benefit from such
      therapies is a natural outgrowth of these discoveries. Development of companion
      diagnostic tests for this identification is proceeding but should receive much
      more attention than it currently does. These tests can simplify the drug
      discovery process, make clinical trials more efficient and informative, and be
      used to individualize the therapy of cancer patients.

PMID- 16900153
TI  - The science-business tango. Interview by Mari Paul.

PMID- 16900158
TI  - Capturing carbon.

PMID- 16900159
TI  - Safeguards for donors.

PMID- 16900160
TI  - Toronto crossroads.

PMID- 16900162
TI  - Ethicists and biologists ponder the price of eggs.

PMID- 16900163
TI  - Health effects of egg donation may take decades to emerge.

PMID- 16900164
TI  - Plan for postdoc union sparks backlash.

PMID- 16900165
TI  - Oil from bombed plant left to spill.

PMID- 16900168
TI  - Views collide over fate of accelerator.

PMID- 16900166
TI  - AIDS vaccine research becomes 'big science'.

PMID- 16900171
TI  - Silent running: the race to the clinic.

PMID- 16900174
TI  - AIDS treatment: staying the course.

PMID- 16900175
TI  - Putting the carbon back: the hundred billion tonne challenge.

PMID- 16900176
TI  - Putting the carbon back: black is the new green.

PMID- 16900177
TI  - Sticking points in the push for change.

PMID- 16900178
TI  - Systems biology could help us harness useful microbes.

PMID- 16900179
TI  - Authors were clear about hockey-stick uncertainties.

PMID- 16900180
TI  - Scientists are well placed to speak up for biodiversity.

PMID- 16900181
TI  - Fair payment or undue inducement?

PMID- 16900187
TI  - Cosmology: where all the lithium went.

PMID- 16900186
TI  - Plant breeding: rice in deep water.

PMID- 16900189
TI  - Solar System: sifting through the debris.

PMID- 16900188
TI  - Materials science: organosilica the conciliator.

PMID- 16900190
TI  - Neurodegenerative disease: cut to the chase.

PMID- 16900191
TI  - Microscopy: nanotomography comes of age.

PMID- 16900193
TI  - A probable stellar solution to the cosmological lithium discrepancy.
AB  - The measurement of the cosmic microwave background has strongly constrained the
      cosmological parameters of the Universe. When the measured density of baryons
      (ordinary matter) is combined with standard Big Bang nucleosynthesis
      calculations, the amounts of hydrogen, helium and lithium produced shortly after
      the Big Bang can be predicted with unprecedented precision. The predicted
      primordial lithium abundance is a factor of two to three higher than the value
      measured in the atmospheres of old stars. With estimated errors of 10 to 25%,
      this cosmological lithium discrepancy seriously challenges our understanding of
      stellar physics, Big Bang nucleosynthesis or both. Certain modifications to
      nucleosynthesis have been proposed, but found experimentally not to be viable.
      Diffusion theory, however, predicts atmospheric abundances of stars to vary with
      time, which offers a possible explanation of the discrepancy. Here we report
      spectroscopic observations of stars in the metal-poor globular cluster NGC 6397
      that reveal trends of atmospheric abundance with evolutionary stage for various
      elements. These element-specific trends are reproduced by stellar-evolution
      models with diffusion and turbulent mixing. We thus conclude that diffusion is
      predominantly responsible for the low apparent stellar lithium abundance in the
      atmospheres of old stars by transporting the lithium deep into the star.

PMID- 16900194
TI  - Occultation of X-rays from Scorpius X-1 by small trans-neptunian objects.
AB  - Since the discovery of the trans-neptunian objects (TNOs) in 1992, nearly one
      thousand new members have been added to our Solar System, several of which are as
      big as--or even larger than--Pluto. The properties of the population of TNOs,
      such as the size distribution and the total number, are valuable information for
      understanding the formation of the Solar System, but direct observation is only
      possible for larger objects with diameters above several tens of kilometres.
      Smaller objects, which are expected to be more abundant, might be found when they
      occult background stars, but hitherto there have been no definite detections.
      Here we report the discovery of such occultation events at millisecond timescales
      in the X-ray light curve of Scorpius X-1. The estimated sizes of these occulting
      TNOs are < or =100 m. Their abundance is in line with an extrapolation of the
      distribution of sizes of larger TNOs.

PMID- 16900195
TI  - Tracking the motion of charges in a terahertz light field by femtosecond X-ray
      diffraction.
AB  - In condensed matter, light propagation near resonances is described in terms of
      polaritons, electro-mechanical excitations in which the time-dependent electric
      field is coupled to the oscillation of charged masses. This description underpins
      our understanding of the macroscopic optical properties of solids, liquids and
      plasmas, as well as of their dispersion with frequency. In ferroelectric
      materials, terahertz radiation propagates by driving infrared-active lattice
      vibrations, resulting in phonon-polariton waves. Electro-optic sampling with
      femtosecond optical pulses can measure the time-dependent electrical
      polarization, providing a phase-sensitive analogue to optical Raman scattering.
      Here we use femtosecond time-resolved X-ray diffraction, a phase-sensitive
      analogue to inelastic X-ray scattering, to measure the corresponding
      displacements of ions in ferroelectric lithium tantalate, LiTaO(3). Amplitude and
      phase of all degrees of freedom in a light field are thus directly measured in
      the time domain. Notably, extension of other X-ray techniques to the femtosecond
      timescale (for example, magnetic or anomalous scattering) would allow for studies
      in complex systems, where electric fields couple to multiple degrees of freedom.

PMID- 16900196
TI  - Supercurrent reversal in quantum dots.
AB  - When two superconductors are electrically connected by a weak link--such as a
      tunnel barrier--a zero-resistance supercurrent can flow. This supercurrent is
      carried by Cooper pairs of electrons with a combined charge of twice the
      elementary charge, e. The 2e charge quantum is clearly visible in the height of
      voltage steps in Josephson junctions under microwave irradiation, and in the
      magnetic flux periodicity of h/2e (where h is Planck's constant) in
      superconducting quantum interference devices. Here we study supercurrents through
      a quantum dot created in a semiconductor nanowire by local electrostatic gating.
      Owing to strong Coulomb interaction, electrons only tunnel one-by-one through the
      discrete energy levels of the quantum dot. This nevertheless can yield a
      supercurrent when subsequent tunnel events are coherent. These quantum coherent
      tunnelling processes can result in either a positive or a negative supercurrent,
      that is, in a normal or a pi-junction, respectively. We demonstrate that the
      supercurrent reverses sign by adding a single electron spin to the quantum dot.
      When excited states of the quantum dot are involved in transport, the
      supercurrent sign also depends on the character of the orbital wavefunctions.

PMID- 16900197
TI  - The dynamics of melt and shear localization in partially molten aggregates.
AB  - The volcanoes that lie along the Earth's tectonic boundaries are fed by melt
      generated in the mantle. How this melt is extracted and focused to the volcanoes,
      however, remains an unresolved question. Here we present new theoretical results
      with implications for melt focusing beneath mid-ocean ridges. By modelling
      laboratory experiments, we test a formulation for magma dynamics and provide an
      explanation for localized bands of high-porosity and concentrated shear
      deformation observed in experiments. These bands emerge and persist at 15 degrees
      25 degrees to the plane of shear. Past theoretical work on this system predicted
      the emergence of melt bands but at an angle inconsistent with experiments. Our
      results suggest that the observed band angle results from a balance of porosity
      weakening and strain-rate-weakening deformation mechanisms. Lower band angles are
      predicted for greater strain-rate weakening. From these lower band angles, we
      estimate the orientation of melt bands beneath mid-ocean ridges and show that
      they may enhance magma focusing toward the ridge axis.

PMID- 16900198
TI  - Synchrotron X-ray tomographic microscopy of fossil embryos.
AB  - Fossilized embryos from the late Neoproterozoic and earliest Phanerozoic have
      caused much excitement because they preserve the earliest stages of embryology of
      animals that represent the initial diversification of metazoans. However, the
      potential of this material has not been fully realized because of reliance on
      traditional, non-destructive methods that allow analysis of exposed surfaces
      only, and destructive methods that preserve only a single two-dimensional view of
      the interior of the specimen. Here, we have applied synchrotron-radiation X-ray
      tomographic microscopy (SRXTM), obtaining complete three-dimensional recordings
      at submicrometre resolution. The embryos are preserved by early diagenetic
      impregnation and encrustation with calcium phosphate, and differences in X-ray
      attenuation provide information about the distribution of these two diagenetic
      phases. Three-dimensional visualization of blastomere arrangement and diagenetic
      cement in cleavage embryos resolves outstanding questions about their nature,
      including the identity of the columnar blastomeres. The anterior and posterior
      anatomy of embryos of the bilaterian worm-like Markuelia confirms its position as
      a scalidophoran, providing new insights into body-plan assembly among constituent
      phyla. The structure of the developing germ band in another bilaterian,
      Pseudooides, indicates a unique mode of germ-band development. SRXTM provides a
      method of non-invasive analysis that rivals the resolution achieved even by
      destructive methods, probing the very limits of fossilization and providing
      insight into embryology during the emergence of metazoan phyla.

PMID- 16900199
TI  - Minimal ProtoHox cluster inferred from bilaterian and cnidarian Hox complements.
AB  - Bilaterian animals have a Hox gene cluster essential for patterning the main body
      axis, and a ParaHox gene cluster. Comparison of Hox and ParaHox genes has led
      workers to postulate that both clusters originated from the duplication of an
      ancient cluster named ProtoHox, which contained up to four genes with at least
      the precursors of anterior and posterior Hox/ParaHox genes. However, the way in
      which genes diversified within the ProtoHox, Hox and ParaHox clusters remains
      unclear because no systematic study of non-bilaterian animals exists. Here we
      characterize the full Hox/ParaHox gene complements and genomic organization in
      two cnidarian species (Nematostella vectensis and Hydra magnipapillata), and
      suggest a ProtoHox cluster simpler than originally thought on the basis of three
      arguments. First, both species possess bilaterian-like anterior Hox genes, but
      their non-anterior genes do not appear as counterparts of either bilaterian
      central or posterior genes; second, two clustered ParaHox genes, Gsx and a gene
      related to Xlox and Cdx, are found in Nematostella vectensis; and third, we do
      not find clear phylogenetic support for a common origin of bilaterian Cdx and
      posterior genes, which might therefore have appeared after the ProtoHox cluster
      duplication. Consequently, the ProtoHox cluster might have consisted of only two
      anterior genes. Non-anterior genes could have appeared independently in the Hox
      and ParaHox clusters, possibly after the separation of bilaterians and
      cnidarians.

PMID- 16900200
TI  - Sub1A is an ethylene-response-factor-like gene that confers submergence tolerance
      to rice.
AB  - Most Oryza sativa cultivars die within a week of complete submergence--a major
      constraint to rice production in south and southeast Asia that causes annual
      losses of over US 1 billion dollars and affects disproportionately the poorest
      farmers in the world. A few cultivars, such as the O. sativa ssp. indica cultivar
      FR13A, are highly tolerant and survive up to two weeks of complete submergence
      owing to a major quantitative trait locus designated Submergence 1 (Sub1) near
      the centromere of chromosome 9 (refs 3, 4, 5-6). Here we describe the
      identification of a cluster of three genes at the Sub1 locus, encoding putative
      ethylene response factors. Two of these genes, Sub1B and Sub1C, are invariably
      present in the Sub1 region of all rice accessions analysed. In contrast, the
      presence of Sub1A is variable. A survey identified two alleles within those
      indica varieties that possess this gene: a tolerance-specific allele named Sub1A
      1 and an intolerance-specific allele named Sub1A-2. Overexpression of Sub1A-1 in
      a submergence-intolerant O. sativa ssp. japonica conferred enhanced tolerance to
      the plants, downregulation of Sub1C and upregulation of Alcohol dehydrogenase 1
      (Adh1), indicating that Sub1A-1 is a primary determinant of submergence
      tolerance. The FR13A Sub1 locus was introgressed into a widely grown Asian rice
      cultivar using marker-assisted selection. The new variety maintains the high
      yield and other agronomic properties of the recurrent parent and is tolerant to
      submergence. Cultivation of this variety is expected to provide protection
      against damaging floods and increase crop security for farmers.

PMID- 16900202
TI  - Validation of a noninvasive neonatal optical cerebral oximeter in veno-venous
      ECMO patients with a cephalad catheter.
AB  - INTRODUCTION: Cerebral Oximetry is an optical technique that allows for
      noninvasive and continuous monitoring of brain oxygenation by determining tissue
      oxygen saturation (SctO2). In conjunction with pulse oximetry, cerebral oximetry
      offers a promising method to estimate cerebral venous oxygen saturation (SvO2).
      OBJECTIVE: The aim of this study was to validate the cerebral oximetry
      measurements with the cerebral oxygen saturation measured from blood drawn in
      neonates on veno-venous ECMO with existing cephalad catheter with a prototype
      neonatal cerebral oximeter developed by CAS Medical Systems (Branford, CT, USA).
      STUDY DESIGN: After obtaining informed consent, neonates undergoing VV-ECMO with
      cephalad catheterization were monitored by the CAS cerebral oximeter. Cephalad
      blood samples were periodically obtained to validate the monitor's accuracy.
      RESULTS: Seventeen neonates were studied with 1718 h of cerebral oximetry data
      collected. Compared to the reference values, the bias+/-precision for cerebral
      oximetry SctO2 was 0.4+/-5.1% and derived SvO2 was 0.6+/-7.3%. CONCLUSION: We
      recommend the use of this noninvasive method as an alternative to blood draws for
      cerebral venous saturation measurements in neonates requiring extracorporeal life
      support.

PMID- 16900203
TI  - Genetic and environmental contributions to plasma C-reactive protein and
      interleukin-6 levels--a study in twins.
AB  - Elevated baseline levels of acute-phase proteins such as C-reactive protein (CRP)
      or cytokines like interleukin-6 (IL-6) are known risk factors for atherosclerosis
      and cardiovascular disease (CVD) events. However, until today, there is only
      controversial information about the contribution of genetic and environmental
      factors. Therefore, we performed an open prospective study in 108 monozygotic
      (MZ) and 60 same-sex dizygotic (DZ) twin pairs to analyse the genetic and
      environmental contributions to plasma CRP and IL-6 levels. Heritability of IL-6
      was 0.61, indicating that plasma IL-6 levels are to a major part influenced by
      genetic determinants; however, for CRP, heritability was only 0.22, pointing to a
      moderate genetic influence. Plasma CRP levels were strongly influenced by female
      gender, older age and especially the body mass index. Our data underline the
      central role of IL-6 in low-grade inflammation contributing to atherosclerosis
      and CVD.

PMID- 16900204
TI  - Genetic susceptibility to polyI:C-induced IFNalpha/beta-dependent accelerated
      disease in lupus-prone mice.
AB  - Systemic lupus erythematosus (SLE) is an autoimmune disease of unknown etiology.
      Associations between viral infections and the onset of SLE have been suggested,
      and recent studies have provided evidence that type I interferons (IFNalpha/beta)
      might play a role in the SLE disease process. Viruses and interferons have also
      been implicated in mouse models of SLE. We generated a model of accelerated
      proteinuria, in which lupus-prone mice were injected repeatedly with
      polyinosinic:polycytidylic acid (polyI:C), mimicking exposure to virus-derived
      double stranded RNA (dsRNA), leading to the production of IFNalpha/beta. PolyI:C
      treated (B6.Nba2 x NZW)F1 and (B6 x NZW)F1 hybrid mice developed significantly
      increased levels of anti-dsDNA autoantibodies, characteristic of lupus. Most
      significantly, polyI:C-treated (B6.Nba2 x NZW)F1 mice, but not (B6 x NZW)F1 or
      parental strains, developed lupus-like nephritis in an accelerated fashion, which
      was dependent on IFNalpha/beta and associated with elevated deposition of total
      IgG, IgG2a and complement factor C3 in the glomerular capillary walls. These data
      suggest that reagents, which increase the levels of endogenous IFNalpha/beta
      (directly or indirectly), can accelerate the course of lupus-like nephritis, the
      development of which is dependent on the presence of both NZW- and Nba2-encoded
      genes.

PMID- 16900205
TI  - Cardiovascular drug use and the incidence of erectile dysfunction.
AB  - It is unclear whether high blood pressure per se or antihypertensive drug use
      causes erectile dysfunction (ED). The aim of this study was to investigate the
      effect of cardiovascular diseases and their concomitant medications use on the
      incidence of ED. The target population consisted of men aged 55, 65 or 75 years
      old residing in the study area in Finland in 1999. Questionnaires were mailed to
      2837 men in 1999 and to 2510 of them 5 years later. The follow-up sample
      consisted of 1665 men (66% of those eligible) who responded to both baseline and
      follow-up questionnaires. Men free of moderate or severe ED at baseline (N=1000)
      were included in the study. ED was assessed by two questions on subject ability
      to achieve or maintain an erection sufficient for intercourse. Poisson regression
      model was used in the multivariable analyses. The risk of ED was higher in men
      suffering from treated hypertension or heart disease than in those with the
      untreated condition. The risk of ED was higher in men using calcium channel
      inhibitor (adjusted relative risk (RR)=1.6, 95% confidence interval (CI) 1.0
      2.4), angiotensin II antagonist (RR=2.2, 95% CI 1.0-4.7), non-selective beta
      blocker (RR=1.7, 95% CI 0.9-3.2) or diuretic (RR=1.3, CI 0.7-2.4) compared with
      non-users. ED was not associated with using organic nitrates, angiotensin
      converting enzyme inhibitors, selective beta-blockers and serum lipid-lowering
      agents. In summary, calcium channel inhibitors, angiotensin II antagonists, non
      selective beta-blockers and diuretics may increase the risk of ED.

PMID- 16900206
TI  - Endothelial microparticles correlate with erectile dysfunction in diabetic men.
AB  - Cell-derived microparticles are supposed to be involved in endothelial
      dysfunction and atherogenesis. This study aimed to evaluate circulating
      microparticles in diabetic subjects with erectile dysfunction (ED) and their
      relation with endothelial dysfunction. Thirty diabetic men with ED and 20 age
      matched control subjects without ED were assessed for circulating microparticles
      and endothelial dysfunction. Flow cytometry was used to assess microparticles by
      quantification of circulating endothelial (EMP, CD31(+)/CD42b(-)) and platelet
      (PMP, CD31(+)/CD42b(+)) microparticles in peripheral blood. Endothelium-dependent
      flow-mediated dilation (FMD) was evaluated in the right brachial artery after
      reactive hyperemia. Compared with non-diabetic subjects, diabetic men presented
      significantly higher numbers of EMP (P=0.001), and reduced FMD (P=0.01), with a
      significant inverse correlation between the number of circulating EMP and the
      International Index of Erectile Function (IIEF) score (r=-0.457, P=0.01).
      Multivariate analysis correcting for age, anthropometric indices, glucose and
      lipid parameters, FMD and PMP identified EMP as the only independent predictor
      for IIEF score (P=0.03). EMP are elevated in impotent diabetic subjects and
      independently involved in the pathogenesis of ED.

PMID- 16900207
TI  - Oncogenic kinases of myeloproliferative disorders induce both protein synthesis
      and G1 activators.

PMID- 16900208
TI  - A microelectronic DNA chip detects the V617F JAK-2 mutation in myeloproliferative
      disorders.

PMID- 16900209
TI  - The pleiotropic effects of the SDF-1-CXCR4 axis in organogenesis, regeneration
      and tumorigenesis.
AB  - Proper response of normal stem cells (NSC) to motomorphogens and chemoattractants
      plays a pivotal role in organ development and renewal/regeneration of damaged
      tissues. Similar chemoattractants may also regulate metastasis of cancer stem
      cells (CSC). Growing experimental evidence indicates that both NSC and CSC
      express G-protein-coupled seven-transmembrane span receptor CXCR4 and respond to
      its specific ligand alpha-chemokine stromal derived factor-1 (SDF-1), which is
      expressed by stroma cells from different tissues. In addition, a population of
      very small embryonic-like (VSEL) stem cells that express CXCR4 and respond
      robustly to an SDF-1 gradient was recently identified in adult tissues. VSELs
      express several markers of embryonic and primordial germ cells. It is proposed
      that these cells are deposited early in the development as a dormant pool of
      embryonic/pluripotent NSC. Expression of both CXCR4 and SDF-1 is upregulated in
      response to tissue hypoxia and damage signal attracting circulating NSC and CSC.
      Thus, pharmacological modulation of the SDF-1-CXCR4 axis may lead to the
      development of new therapeutic strategies to enhance mobilization of CXCR4+ NSC
      and their homing to damaged organs as well as inhibition of the metastasis of
      CXCR4+ cancer cells.

PMID- 16900210
TI  - Promoter DNA methylation of CD10 in lymphoid malignancies.

PMID- 16900211
TI  - Serpin A1 is overexpressed in ALK+ anaplastic large cell lymphoma and its
      expression correlates with extranodal dissemination.
AB  - Anaplastic large cell lymphoma (ALCL) is a distinct subtype of non-Hodgkin's
      lymphoma. Most of ALCLs (85%) carry a chromosomal translocation involving
      different partners in the 5' portion, and the anaplastic lymphoma kinase (ALK)
      receptor kinase domain in the 3' portion. These translocations induce the ectopic
      expression of X-ALK proteins, thought to be involved in lymphomagenesis, through
      the dysregulation of cell proliferation and apoptotic pathways. In the present
      study, based on several ALK+ and ALK- ALCL cell lines and biopsy specimens, we
      showed that serpin A1, a secretory glycoprotein, was overexpressed in ALK+ ALCL
      cell lines and ALK+ tumors at both the transcriptional and translational levels.
      The crucial role of NPM-ALK in the regulation of serpin A1 expression was further
      demonstrated by using both ectopic expression and downregulation, by RNA
      interference, of the NPM-ALK oncogene. In addition, in ALK+ tumors, serpin A1
      expression appeared to be correlated with the clinical status of the patients as
      the serpin A1 mRNA level was higher in patients presenting with extranodal
      dissemination. These data, together with the pattern of expression of serpin A1
      we observed in ALK+ tumors, suggest that serpin A1 has an invasion-promoting
      effect in ALK+ ALCL.

PMID- 16900212
TI  - Most immature T-ALLs express Ra-IL3 (CD123): possible target for DT-IL3 therapy.

PMID- 16900213
TI  - Differential DNA methylation patterns of small B-cell lymphoma subclasses with
      different clinical behavior.
AB  - Non-Hodgkin's lymphoma (NHL) is a group of malignancies of the immune system with
      variable clinical behaviors and diverse molecular features. Despite the progress
      made in classification of NHLs based on classical methods, molecular
      classifications are a work in progress. Toward this goal, we used an array-based
      technique called differential methylation hybridization (DMH) to study small B
      cell lymphoma (SBCL) subtypes. A total of 43 genomic DMH experiments were
      performed. From these results, several statistical methods were used to generate
      a set of differentially methylated genes for further validation. Methylation of
      LHX2, POU3F3, HOXC10, NRP2, PRKCE, RAMP, MLLT2, NKX6.1, LRP1B and ARF4 was
      validated in cell lines and patient samples and demonstrated subtype-related
      preferential methylation patterns. For LHX2 and LRP1B, bisulfite sequencing, real
      time reverse transcriptase-polymerase chain reaction and induction of gene
      expression following treatment with the demethylating agent, 5'-aza-2'
      deoxycytidine, were confirmed. This new epigenetic information is helping to
      define molecular portraits of distinct subtypes of SBCL that are not recognized
      by current classification systems and provides valuable potential insights into
      the biology of these tumors.

PMID- 16900214
TI  - Endothelial cell-driven regulation of CD9 or motility-related protein-1
      expression in multiple myeloma cells within the murine 5T33MM model and myeloma
      patients.
AB  - The cell surface expression of CD9, a glycoprotein of the tetraspanin family
      influencing several processes including cell motility and metastasis, inversely
      correlates with progression in several solid tumors. In the present work, we
      studied the expression and role of CD9 in multiple myeloma (MM) biology using the
      5T33MM mouse model. The 5T33MMvitro cells were found to be CD9 negative.
      Injection of these cells in mice caused upregulation of CD9 expression, while
      reculturing them resulted in downregulation of CD9. Coculturing of CD9-negative
      5T33MMvitro cells with BM endothelial cells (BMECs) resulted in a partial
      retrieval of CD9. Laser microdissection followed by real-time polymerase chain
      reaction and immunohistochemistry performed on bone sections of 5T33MMvivo
      diseased mice demonstrated strong local expression of CD9 on MM cells in contact
      with BMEC compared to MM cells further away. These findings were also confirmed
      by immunohistochemistry in MM patients. Neutralizing anti-CD9 antibodies
      inhibited transendothelial invasion of CD9-expressing human MM5.1 and murine
      5T33MMvivo cells. In conclusion, we provide evidence that CD9 expression by the
      MM cells is upregulated in vivo by close interaction of the cells with BMEC and
      that CD9 is involved in transendothelial invasion, thus possibly mediating homing
      and/or spreading of the MM cells.

PMID- 16900216
TI  - One physician's exploration of the ethics in the practice of medicine.

PMID- 16900217
TI  - Retrocaval ureter.

PMID- 16900218
TI  - Treatment of proliferative lupus nephritis: a changing landscape.
AB  - Grootscholten et al. report a randomized controlled trial comparing azathioprine
      plus intravenous methylprednisolone and oral prednisolone (AZA group) with
      intermittent intravenous cyclophosphamide and oral prednisolone (CY group) in
      patients with proliferative lupus nephritis. AZA-treated patients were more
      likely to develop non-sustained doubling of their serum creatinine, although not
      significantly so, and significantly more likely to have a relapse of their
      nephritis than CY-treated patients.

PMID- 16900219
TI  - Increased cyclooxygenase-2, hyperfiltration, glomerulosclerosis, and diabetic
      nephropathy: put the blame on the (pro)renin receptor?
AB  - Interaction between the renin-angiotensin system and cyclooxygenases in the
      kidney regulates renal microcirculation. Activation of the (pro)renin receptor
      has profibrotic effects, and now Kaneshiroet al. show that it also increases COX
      2 synthesis. These results may have therapeutic implications, as blocking
      (pro)renin-receptor interaction would prevent the increase of angiotensin
      generation and prostaglandin synthesis, two phenomena underlying the pathogenesis
      of diabetic nephropathy.

PMID- 16900220
TI  - The clot thickens.
AB  - Vascular sclerosis has been linked to many risk factors, including smoking,
      family history, low birth weight, and hypertension. In interesting studies,
      Goforth et al. show an increased rate of mutations in thrombophilic molecules in
      patients with vascular sclerosis in renal biopsies, suggesting yet another
      mechanism.

PMID- 16900222
TI  - Hepatitis B-related membranous nephropathy should be treated with a specific anti
      viral agent.

PMID- 16900224
TI  - Polymer conjugates as anticancer nanomedicines.
AB  - The transfer of polymer-protein conjugates into routine clinical use, and the
      clinical development of polymer-anticancer-drug conjugates, both as single agents
      and as components of combination therapy, is establishing polymer therapeutics as
      one of the first classes of anticancer nanomedicines. There is growing optimism
      that ever more sophisticated polymer-based vectors will be a significant addition
      to the armoury currently used for cancer therapy.

PMID- 16900225
TI  - Effects of ingesting a high-fat diet upon exercise-training cessation on fat
      accretion in the liver and adipose tissue of rats.
AB  - The purpose of the present study was to determine if exercise trained rats might
      benefit from protection against fat accumulation in response to an obesity
      stimulus initiated upon training cessation. Two groups of female rats were either
      treadmill trained for 8 weeks (DTr) or remained sedentary (Sed). They were then
      submitted either to a high-fat diet (HF; 42 E%) or kept on a standard diet (SD;
      12.5 E% lipids) for another 6 weeks while remaining sedentary. Fat accumulation
      in liver and adipocytes along with fat-cell diameter and plasma free fatty acid
      (FFA) levels were measured 0, 2, and 6 weeks after training cessation.
      Immediately after the training period (t = 0), DTr rats exhibited similar body
      mass and higher dietary intake but smaller body fat content (4 fat pads) compared
      with Sed rats. DTr rats, under both diets, exhibited higher gains in body fat
      than Sed rats (DTr vs. Sed, 71% vs. 8% and 132% vs. 55% for SD and HF,
      respectively), such that fat mass in all 4 depots was similar to Sed rats 6 weeks
      after training cessation. Despite higher adipocyte fat accretion, liver lipid
      infiltration was not increased in DTr animals and plasma FFA levels were lower
      throughout the detraining period. In addition, plasma leptin levels remained
      lower in DTr animals throughout the detraining period under the HF diet
      condition. The present results indicate that previously exercise trained rats are
      not protected against adipocyte fat accumulation whether they ingest a standard
      or a high-fat diet.

PMID- 16900223
TI  - A heparan sulfate-targeted conditionally replicative adenovirus, Ad5.pk7-Delta24,
      for the treatment of advanced breast cancer.
AB  - Conditionally replicating adenoviruses (CRAds) that replicate in tumor but less
      in normal cells are promising anticancer agents. A major determinant of their
      potency is their capacity for infecting target cells. The primary receptor for
      serotype 5 adenovirus (Ad5), the most widely used serotype in gene therapy, is
      the coxsackie-adenovirus receptor (CAR). CAR is expressed variably and often at
      low levels in various tumor types including advanced breast cancer. We generated
      a novel p16/retinoblastoma pathway-dependent CRAd, Ad5.pK7-Delta24, with a
      polylysine motif in the fiber C-terminus, enabling CAR-independent binding to
      heparan sulfate proteoglycans (HSPG). Ad5.pK7-Delta24 mediated effective
      oncolysis of all breast cancer cell lines tested. Further, we utilized
      noninvasive, fluorescent imaging for analysis of antitumor efficacy in an
      orthotopic model of advanced hormone refractory breast cancer. A therapeutic
      benefit was seen following both intratumoral and intravenous delivery. Murine
      biodistribution similar to Ad5, proven safe in trials, suggests feasibility of
      clinical safety testing. Interestingly, upregulation of CAR was seen in low-CAR
      M4A4-LM3 breast cancer cells in vivo, which resulted in better than expected
      efficacy also with an isogenic CRAd with an unmodified capsid. These results
      suggest utility of Ad5.pK7-Delta24 and the orthotopic model for further
      translational studies.

PMID- 16900226
TI  - Changes in muscle activity and perceived exertion during exercises performed on a
      swiss ball.
AB  - The objective of this study was to determine differences in electromyographic
      (EMG) activity of prime mover and abdominal muscles while performing squats, push
      ups, and double leg lowering with a swiss ball. Twelve healthy subjects performed
      the movements. There was no difference between the surface conditions for muscle
      activity during the squat exercise; however, individuals had lower perceived
      exertion for the swiss ball squat. Activity of the triceps and abdominals was
      highest performing push ups on the swiss ball, whereas the activity of rectus
      abdominus (RA) only increased during double leg lowering on the swiss ball.
      Perceived exertion was highest for the push up and leg-lowering exercise
      performed on the swiss ball. Increased RA activity during double leg lowering can
      be attributed to its role as a hip flexor, whereas the lack of a rotation aspect
      to the task prevented increased oblique muscle activity. The swiss ball appears
      to only increase muscle activity during exercises where the unstable surface is
      the primary base of support.

PMID- 16900227
TI  - Effects of exercise and nutritional counseling in women with polycystic ovary
      syndrome.
AB  - This pilot study assessed the effects of exercise and nutritional counseling on
      hormonal, menstrual, and reproductive function in women with polycystic ovary
      syndrome (PCOS). Twelve females with a clinical, biochemical, and
      ultrasonographic diagnosis of PCOS were randomly assigned to endurance and
      resistance exercise plus nutritional counseling (EN) or nutritional counseling
      only (N) for a period of 12 weeks. Anthropometry, resting metabolic rate (RMR),
      selected hormones, and ovarian follicle population were measured pre and post
      intervention. Following the 12 week intervention, greater decreases in sum of 2
      skinfolds (p = 0.002) and a greater increase in estimated VO2 max (p = 0.017)
      occurred in the exercise group. Significant decreases in waist girth (p = 0.001)
      and insulin levels (p = 0.03) occurred in both groups. Hormonal changes were not
      statistically significant; however, a trend towards an improved hormonal profile,
      specifically sex-hormone binding globulin (EN, 39% increase; N, 8% increase) and
      lutenizing hormone : follicle-stimulating hormone (LH:FSH) (EN, 9% decrease; N,
      27% decrease) occurred in the absence of weight loss. These findings suggest
      exercise and nutritional counseling may benefit the metabolic and reproductive
      abnormalities associated with PCOS.

PMID- 16900228
TI  - Determination of aerobic work and power on a rope-braked cycle ergometer by
      direct measurement.
AB  - The purpose of this study was to compare the power and work outputs of a cycle
      ergometer using the manufacturer's guidelines, with calculations using direct
      flywheel velocity and brake torque. A further aim was to compare the values
      obtained with those supplied by the manufacturer. A group of 10 male participants
      were asked to pedal a Monark 824E ergometer at a constant cadence of 60 r/min for
      a period of 3 min against a resistive mass of 3 kg. The flywheel velocity was
      measured using a tachometer. The brake force was determined by measuring the
      tension in the rope on either side of the flywheel. The calculated mean power was
      147.45 +/- 6.5 W compared with the Monark value of 183 +/- 3.7 W. The difference
      between the methods for power estimation was 18% and was statistically
      significant (p < 0.01). The mean work done by the participants during the 3 min
      period was found to be 26 460 +/- 1145 J compared with the Monark value of 33,067
      +/- 648 J (p < 0.01). The Monark formulae currently used to determine the power
      and work done by a participant overestimates the actual values required to
      overcome the resistance. There findings have far-reaching implications in the
      physiological assessment of athletic, sedentary, and diseased populations.

PMID- 16900229
TI  - Early effects of spinal cord transection on skeletal muscle properties.
AB  - Modulation of beta-adrenergic receptor (beta-AR) activity affects muscle mass and
      could have a role in the reduction of muscle mass observed following spinal cord
      transection (Tx). The aims of this study were to examine the early acute effects
      of Tx on muscle mass, total and myofibrillar protein concentrations, cytochrome c
      oxidase activity, and beta-AR density of skeletal muscle, to ascertain if any
      change in muscle properties could be related to beta-AR signalling events. Female
      Sprague-Dawley rats (n = 33; approximately 255 g) were randomly assigned to 4
      experimental groups: control 4 d, control 8 d, Tx 4 d, and Tx 8 d. A complete Tx
      was performed surgically at the T10 cord level. Compared with controls, muscle
      mass and muscle - body mass ratios decreased significantly following Tx, with no
      significant change observed in total and myofibrillar protein concentrations.
      Spinal cord Tx also resulted in a significant decrease in plantaris cytochrome c
      oxidase activity by 24% at Tx 4 d and 28% at Tx 8 d (p < 0.05). Beta-AR density
      of the lateral gastrocnemius was unchanged; however, the beta-AR density of the
      forelimb triceps brachii m. was found to increase after Tx. Our results suggest
      that changes in muscle mass and cytochrome c oxidase activity rapidly occur after
      Tx and do not appear to be related to changes in beta-AR density.

PMID- 16900230
TI  - Physical activity during treatment in children with leukemia: a pilot study.
AB  - The purpose of this pilot study was to measure physical activity (PA) levels in
      children undergoing treatment for acute lymphoblastic leukemia (ALL) and to
      compare the results with those from age-matched healthy children. We used the MTI
      Actigraph accelerometer to determine PA (during a 1 week period) in children (n =
      7; age = 4-7 y) undergoing maintenance treatment for ALL and in age-matched
      controls (n = 7). The number of children accumulating at least 60 min of moderate
      to-vigorous physical activity (MVPA) for 5 or more days of the week was 3 for the
      control group, whereas no children with ALL met this criterion. Significantly
      lower levels of total weekly time of MVPA were seen in children being treated for
      ALL (328 +/- 107 min) than in controls (506 +/- 175 min) (p < 0.05). When weekday
      data was analyzed, the ALL patients also had significantly lower mean daily times
      of MVPA (49 +/- 23 min vs. 79 +/- 25 min). It is thus important that young ALL
      sufferers are encouraged to participate in appropriate sports, games, and
      physical activities both in the family and school environments that will prime
      them with positive attitudes to PA during the critical early years of life.

PMID- 16900231
TI  - Is the VO2 slow component in heavy arm-cranking exercise associated with
      recruitment of type II muscle fibers as assessed by an increase in surface EMG?
AB  - The recruitment of additional type II muscle fibers is one mechanism often
      suggested to be responsible for the slow component of oxygen uptake (VO2 (SC)).
      We hypothesized that surface electromyogram (EMG) of the biceps brachii, triceps
      brachii, anterior deltoid, and infraspinatus muscles could be related to the VO2
      (SC) amplitude during arm-cranking exercises above ventilatory threshold (VT).
      Eight healthy subjects performed transitions from rest to 6-min heavy exercise at
      a constant power output of approximately 40% between VT and peak VO2. A 2
      component exponential model was used to fit the VO2 response. EMG were recorded
      the last 15 s of each minute to obtain root mean square (RMS) and mean power
      frequency (MPF). Mean EMG responses for RMS and MPF were calculated by averaging
      EMG responses of the 4 muscles. The VO2 (SC) amplitude was of 530 +/- 166 mL/min
      and occurred after 134 +/- 31 s of exercise onset. Significant correlations were
      found for most of the subjects between EMG parameters and the VO2 SC amplitude as
      determined between the 2nd and the 6th minute. For all muscles, RMS values
      significantly increased over time during the VO2 (SC), whereas MPF decreased
      significantly. These results suggest a relation between the recruitment of
      additional type II muscle fibers and the VO2 (SC) in arm-cranking exercises.

PMID- 16900232
TI  - Effect of differences in post-exercise lactate accumulation in athletes'
      haemodynamics.
AB  - To verify the relationship between exercise intensity and post-exercise
      haemodynamics, we studied haemodynamic and lactate responses during 10 min
      following 3 bicycle tests. Two tests were performed for 3 min at 70% and 130% of
      the workload corresponding to anaerobic threshold (70% W(at) and 130% W(at)
      tests), and 1 was performed until exhaustion at 150% of the maximum workload
      achieved during a previous incremental test (150% W(max) test). During the
      recovery period after the 150% W(max) test we observed the highest increases in
      blood lactate with respect to the baseline: at the 9th minute of recovery lactate
      concentration increased by +9.3 +/- 2.7, +6.4 +/- 3.1, and +1.1 +/- 0.9 mmol x L(
      1) in the 150% W(max) (p > 0.05 with respect to the other protocol sessions),
      130% W(at), and 70% W(at) tests, respectively. We also observed greater
      reductions in cardiac pre-load and systemic vascular resistance in the 150%
      W(max) test than in the 130% W(at) and 70% W(at) tests. However, the cardiac
      output response successfully faced the increased vasodilatation occurring during
      150% W(max) test so that changes in mean blood pressure were similar in the 3
      test conditions. This study shows that exercises that yielded different lactate
      concentrations also led to greater vasodilatation. Nevertheless, mechanisms
      controlling the cardiovascular apparatus successfully prevented a drop in blood
      pressure in spite of the cardiovascular stress.

PMID- 16900234
TI  - [Effects of puberty on glucose-lipid balance during exercise in the obese child].
AB  - The aim of the present study was to investigate effect of puberty on substrate
      oxidation rates using a graded exercise test to exhaustion. Two groups of obese
      adolescent males (34 prepubertal: body mass index (BMI) = 25,94 +/- 2,63; Z-score
      = 4,43 +/- 1,83; and 26 postpubertal: BMI = 31,14 +/- 4,88; Z-score = 5,264 +/-
      1,76) performed an exercise test on a cycle ergometer. The test consisted in a
      series of graded exercises on a cycle ergometer. Stage duration was 3 min 30 s.
      Fat and carbohydrate rates were calculated during the last 30 s of each stage
      using stoichiometric equations, and this permitted us to calculate substrate
      oxidation according to exercise intensity. Lipid oxidation rates are
      significantly higher in the postpubertal group. When the fat oxidation rates are
      reported relative to fat free mass, fat oxidation rates are higher in the
      prepubertal group. Puberty decreases significantly the capacity of fat free mass
      to oxidize fat for a same level of exercise.

PMID- 16900233
TI  - Effects of physical conditioning on lipids and arachidonic acid metabolites in
      untrained boys: a longitudinal study.
AB  - In addition to a variety of lipids, 2 products of the arachidonic acid cascade,
      prostacyclin and thromboxane, are involved in the pathogenesis of atherosclerosis
      as a result of their effects on platelet function and on the vascular
      endothelium. The aim of the present investigation was to ascertain if a sub
      maximal 8 week endurance training period followed by a 4 week detraining period
      would have any effects on high-density lipoprotein cholesterol (HDL-C), total
      cholesterol (TC), triglycerides (TG), 2,3-dinor-6-keto-prostaglandin F(1alpha)
      (2,3-dinor-6-keto-PGF(1alpha)), the urinary metabolite of prostacyclin, 2,3-dinor
      thromboxane B2 (2,3-dinor-TXB2), the urinary metabolite of thromboxane, and the
      ratios of TC to HDL-C and of 2,3 dinor-6-keto-PGF(1alpha) to 2,3-dinor-TXB2.
      Thirty-eight boys aged 10-14 were randomly divided into exercise (n = 21) and
      control (n = 17) groups. The exercise group trained on a bicycle ergometer 4
      times/week, 1 h/session, at 80% of their physical working capacity at a heart
      rate of 170 beats/min (PWC(170)), for 8 weeks. The control group did not
      participate in any specific physical exercise program. The results showed that
      relative to the control group, the exercise group had a significant increase in
      HDL-C and 2,3-dinor-6-keto-PGF(1alpha) concentrations at the end of the 4th (p <
      0.05 and p < 0.001, respectively) and the 8th week (p < 0.01 and p < 0.001) of
      training, respectively; a significant increase in the 2,3 dinor-6-keto
      PGF(1alpha) - 2,3-dinor-TXB2 ratio (p < 0.05 and p < 0.01 at the same intervals);
      a significant decrease in TG at the end of the 8th week of training (p < 0.05);
      and a significant decrease in the TC--HDL-C ratio at the end of the 4th (p <
      0.05) and 8th weeks of training (p < 0.001).

PMID- 16900235
TI  - Soleus muscle force following downhill running in ovariectomized rats treated
      with estrogen.
AB  - The ovariectomized (OVX) rat model was used to investigate the effects of
      estrogen treatment on soleus muscle functionality in situ following muscle injury
      induced by downhill running. Fifty immature, 24- to 26-d-old, OVX rats were
      randomly assigned to 5 separate experimental groups: sedentary controls (OVX
      Sed), placebo-treated and studied immediately after exercise (OVX-Pb0), placebo
      treated and studied 72 h after exercise (OVX-Pb72), estradiol-treated and studied
      immediately after exercise (OVX-Ed0), and estradiol-treated and studied 72 h
      after exercise (OVX-Ed72). At the age of 9 weeks, under ketamine and xylazine
      anesthesia i.p., the rats were subcutaneously implanted with either placebo or
      17beta-estradiol-impregnated pellets (0.05 mg/pellet, 3 week release). Treatment
      with 17beta-estradiol increased the estradiol plasma levels in OVX animals to
      those normally seen during the proestrous cycle of normal animals. Three weeks
      after the implantation the rats were subjected to a 90 min intermittent downhill
      running protocol. Our results indicate that the exercise protocol used in the
      study induced injury in the soleus muscle, as it was detected by the significant
      reduction in unfused (stimulation at 10, 20, and 40 Hz) and maximal (Po) tetanic
      force, as well as the decreased ability of the soleus muscle to maintain tension
      (stimulation at 40 Hz for 3 min) in OVX-Pb0 and OVX-Pb72 placebo-treated animals
      subjected to downhill running (injured muscles) as compared with OVX-Sed control
      rats (uninjured muscle). Estradiol replacement in OVX rats partially protected
      the soleus muscle from the injury normally induced by downhill running. As
      compared with the OVX-Pb0 and OVX-Pb72 placebo-treated groups, the soleus muscles
      of OVX-Ed0 and OVX-Ed72 estradiol-treated rats were capable of producing
      significantly greater unfused tetanic force and had an increased ability to
      maintain tension after fatigue. However, estrogen at the dose administered did
      not prevent the decrease in maximal tetanic force. We postulate that the
      protective effect of estrogens on muscle strength may be related to the ability
      of estrogen hormones to attenuate the E--C coupling failure and (or) the
      disorganization of the contractile apparatus associated with eccentric exercise
      through a mechanism or mechanisms yet to be fully understood.

PMID- 16900236
TI  - Airway distensibility in normal and asthmatic subjects and partitioning of the
      Fowler dead space.
AB  - Anatomical dead space measured by the Fowler method (VDF) is the sum of 2 serial
      volume compartments (VDF = VDp1 + VDp2). VDF has been shown to increase linearly
      with end-inspiratory lung volume (EILV) and the gradient of the relationship
      (DeltaVDF) has been used as an index of airway distensibility. The aim of this
      study was to partition VDF into its serial compartments VDp1 and VDp2 to test the
      hypothesis that, given the greater distensibility of distal airways, VDp2 would
      demonstrate greater volume dependence than VDp1. The relationships between each
      measure of VD (VDF, VDp1, and VDp2) and EILV were studied in 16 healthy subjects
      and 16 mildly asthmatic subjects. Significant (p < 0.05) linear relationships
      were obtained between each measure of VD and EILV in both subject groups. Changes
      in VDp1 with EILV (DeltaVDp1) accounted for 78.6% +/- 5.6% (mean +/- SEM) and
      72.6% +/- 6.3% of DeltaVDF in the healthy and asthmatic groups, respectively.
      DeltaVDp1 was greater in the healthy subjects than in asthmatic subjects (18.4
      versus 13.1 mL/L, p = 0.005). We conclude that in both asthmatic and healthy
      subjects, the major component of DeltaVDF was DeltaVDp1 and not DeltaVDp2, as
      originally hypothesized. We believe our results are reflecting the degree of
      asynchronous airway emptying.

PMID- 16900237
TI  - Viability of the isolated soleus muscle during long-term incubation.
AB  - Skeletal muscle metabolism has been examined in perfused hindlimb muscles and in
      isolated muscle preparations. While long-term viability of the fast-twitch
      epitrochlearis has been documented with respect to glucose transport, it appears
      that long-term incubated soleus muscles are less stable when incubated ex vivo
      for many hours. Therefore, in the present study, we have examined whether the
      isolated soleus muscle remains metabolically viable for up to 18 h with respect
      to maintaining ATP and phosphocreatine (PCr) concentrations, carbohydrate and
      fatty-acid metabolism, insulin signalling, and protein expression. Soleus muscles
      were incubated in well-oxygenated Medium 199 (M199) supplemented with low
      concentrations of insulin (14.3 microU/mL) for 0, 6, 12, and 18 h. During this
      incubating period the concentrations of ATP and PCr were stable, indicating that
      oxygenation and substrate supply were being maintained. In addition, the
      concentrations of proglycogen and macroglycogen were not altered, whereas an
      increase (+30%) in intramuscular triacylglycerol concentration was observed at
      the end of 18 h of incubation (p < 0.05). Complex molecular processes in the long
      term incubated muscles were also stable. This was shown by maintenance of basal
      as well as insulin-stimulated rates of 3-O-methyl glucose transport, and by the
      maintenance of protein expression of the glucose transporter GLUT4 and the fatty
      acid transporters FAT/CD36 and FABPpm. In addition, the insulin-stimulated
      translocation of GLUT4 to the plasma membrane, which involves a complex
      signalling cascade, was fully preserved. In conclusion, in well-oxygenated soleus
      muscles maintained in M199 supplemented with extremely low concentrations of
      insulin, ATP and PCr concentrations, carbohydrate and fatty acid metabolism,
      insulin signalling, and protein expression were stably maintained for up to 18 h.
      This provides for opportunities to examine muscle metabolic function under very
      highly controlled conditions.

PMID- 16900242
TI  - Inhibitory effects of astragaloside IV on diabetic peripheral neuropathy in rats.
AB  - Astragaloside IV (AGS-IV), a new glycoside of cycloartane-type triterpene
      isolated from the root of Astragalus membranaceus (Fisch.) Bunge, has been used
      experimentally for its potent immune-stimulating, anti-inflammatory, and
      antioxidative actions. A recent study has shown AGS-IV to be an aldose-reductase
      inhibitor and a free-radical scavenger. This study examined the effects of AGS-IV
      on motor nerve conduction velocity (MNCV), tailflick threshold temperature,
      biochemical indexes, and the histology of the sural nerve after diabetes was
      induced in rats with 75 mg/kg streptozotocin (STZ). AGS-IV (3, 6, 12 mg/kg, twice
      a day) was administered by oral gavage for 12 weeks after diabetes was induced.
      Compared with control (nondiabetic) rats, obvious changes in physiological
      behaviors and a significant reduction in sciatic MNCV in diabetic rats were
      observed after 12 weeks of STZ administration. Morphological analysis showed that
      AGS-IV suppressed a decrease in myelinated fiber area, an increase in myelinated
      fiber density, and an increase in segmental demyelination in diabetic rats. The
      protective mechanism of AGS-IV involved a decrease in declining blood glucose
      concentration and HbA1C levels, and an increase in plasma insulin levels. AGS-IV
      increased the activity of glutathione peroxidase in nerves, depressed the
      activation of aldose reductase in erythrocytes, and decreased the accumulation of
      advanced glycation end products in both nerves and erythrocytes. Moreover, AGS-IV
      elevated Na+,K+-ATPase activity in both the nerves and erythrocytes of diabetic
      rats. These results indicate that AGS-IV exerts protective effects against the
      progression of peripheral neuropathy in STZ-induced diabetes in rats through
      several interrelated mechanisms.

PMID- 16900244
TI  - Early activation and redistribution of calpain activity in skeletal muscle during
      hindlimb unweighting and reweighting.
AB  - The aims of this study were the following: (i) to determine whether activation of
      the Ca2+-activated protease, calpain, is an early event during hindlimb
      unweighting (HU) in skeletal muscle; and (ii) to assess whether calpain activity
      is greater during reweighting compared with HU alone. Rats were exposed to 12,
      24, and 72 h, or 9 d of HU, followed by reweighting for 0, 12, or 24 h. Calpain
      activities were assayed for total, soluble, and particulate fractions. Total
      calpain activity was increased in the soleus at all HU time points, whereas
      activities were elevated in the gastrocnemius only after 9 d of HU. With
      reweighting, calpain activity remained elevated at all time points for both
      muscles. In general, reweighting the gastrocnemius increased its calpain activity
      more than during HU only, whereas reweighting the soleus did not produce
      additional increases in its calpain activity. The increases in calpain activity
      were associated with a proportional increase in activity of the particulate
      (membrane- and protein-associated) fraction. The results suggest that calpain
      activation is an early event during HU in the soleus, and that the increases in
      calpain activity in both muscles are associated with a redistribution of activity
      from cytosolic to particulate fractions.

PMID- 16900243
TI  - Sodium-, chloride-, and mibefradil-sensitive calcium channels in intestinal
      pacing in wild-type and W/WV mice.
AB  - Pacing of intestinal smooth muscle is driven by a network of cells found in the
      myenteric plexus called the interstitial cells of Cajal (ICC-MP), which produce a
      rhythmic pacemaker current. Using intact segments of circular (CM) and
      longitudinal (LM) muscle from wild-type and W/WV mice, we found that sodium-,
      chloride-, and mibefradil-sensitive ion channel currents are required for normal
      pacing to occur. Application of 30 micromol/L and 300 micromol/L lidocaine, 1
      mmol/L 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS), 50 nmol/L and
      500 nmol/L mibefradil, or low sodium Krebs significantly reduced pacing frequency
      in LM and CM. However, simultaneously applying DIDS and lidocaine or low sodium
      Krebs solution did not completely block pacing nor did it have an additive
      effect. Lidocaine and low sodium Krebs solution also abolished the gradient of
      pacing frequencies (higher proximally) found throughout the intestine, resulting
      in a uniform contraction frequency of 30-40/min. In W/WV mice, which lack ICC-MP,
      application of DIDS and lidocaine had no effect on the robust pacing in LM
      segments. In conclusion we found that sodium-, chloride-, and mibefradil
      sensitive channel activities were required for normal pacing and to maintain the
      pacing gradient found throughout the intestines in wild-type but not W/WV mice.

PMID- 16900245
TI  - Postconditioning fails to prevent radial artery endothelial dysfunction induced
      by ischemia and reperfusion: evidence from a human in vivo study.
AB  - Animal studies have shown that, as compared with unrestricted reperfusion,
      exposure to brief periods of controlled ischemia (postconditioning) at the end of
      a prolonged ischemia reduces the extent of tissue damage. We set out to test
      whether postconditioning can prevent endothelial dysfunction induced by ischemia
      and reperfusion in a human in vivo model. Ten healthy young non-smoking
      volunteers were enrolled in this cross-over, controlled, investigator-blinded
      study. Subjects were exposed to 15 min of forearm ischemia followed by either
      unrestricted reperfusion or postconditioning (3 periods of 20 s of ischemia
      separated by 10 s of reperfusion). Endothelium-dependent flow-mediated dilation
      (FMD) was measured at the level of the radial artery before and after ischemia
      (with or without postconditioning). Forearm ischemia blunted FMD in both study
      visits (unrestricted reperfusion visit: before ischemia, 7.7% +/- 1.3%; after
      ischemia, 2.5% +/- 1.4%; and postconditioning visit: before, 7.3% +/- 1.2%;
      after, 2.6 +/- 1.6%; P < 0.05 for both, P = not significant (NS) between visits).
      In contrast with data from animal studies, postconditioning (20 s ischemia-- 10 s
      reperfusion repeated 3 times) does not limit post-ischemic endothelial
      dysfunction in this human in vivo model. Further human studies are necessary to
      evaluate other reperfusion protocols in an attempt to limit post-ischemic tissue
      damage.

PMID- 16900246
TI  - Magnesium deficiency augments myocardial response to reactive oxygen species.
AB  - Magnesium (Mg) deficiency and oxidative stress are independently implicated in
      the etiopathogenesis of various cardiovascular disorders. This study was
      undertaken to examine the hypothesis that Mg deficiency augments the myocardial
      response to oxidative stress. Electrically stimulated rat papillary muscle was
      used for recording the contractile variation. Biochemical variables of energy
      metabolism (adenosine triphosphate (ATP) and creatine phosphate) and markers of
      tissue injury (lactate dehydrogenase (LDH) release and lipidperoxidation), which
      can affect myocardial contractility, were assayed in Langendorff-perfused rat
      hearts. Hydrogen peroxide (100 micromol/L) was used as the source of reactive
      oxygen species. The negative inotropic response to H2O2 was significantly higher
      in Mg deficiency (0.48 mmol Mg/L) than in Mg sufficiency (1.2 mmol Mg/L). Low Mg
      levels did not affect ATP levels or tissue lipid peroxidation. However, H2O2
      induced a decrease in ATP; enhanced lipid peroxidation and the release of LDH
      were augmented by Mg deficiency. Increased lipid peroxidation associated with a
      decrease in available energy might be responsible for the augmentation of the
      negative inotropic response to H2O2 in Mg deficiency. The observations from this
      study validate the hypothesis that myocardial response to oxidative stress is
      augmented by Mg deficiency. This observation has significance in ischemia
      reperfusion injury, where Mg deficiency can have an additive effect on the
      debilitating consequences.

PMID- 16900247
TI  - Effect of AT2 blockade on cardiac hypertrophy as induced by high dietary salt in
      the proatrial natriuretic peptide (ANP) gene-disrupted mouse.
AB  - The role of the angiotensin II type 2 receptor (AT2) during alterations in
      cardiac size remains largely unclear. Through employment of an AT2 antagonist,
      the present study explored a possible involvement of the AT2 receptor during salt
      induced cardiac hypertrophy in the proatrial natriuretic peptide gene-disrupted
      mouse (ANP-/-). ANP-/- mice received either saline solution or the AT2
      antagonist, PD123319, and were then placed on a high salt diet (8.0% NaCl) for 3
      weeks. Cardiac and pulmonary size, expression of the renin-angiotensin system
      (RAS), and the behaviour of various hypertrophy marker genes were assessed.
      PD123319 caused enhanced expression of the systemic RAS, yet the cardiac RAS was
      largely unaffected. Although AT2 blockade did not alter whole cardiac mass, right
      ventricle mass, as well as pulmonary mass-to-body mass ratios were significantly
      decreased. Collagen type I was decreased in the latter tissues, likely
      contributing to the regression in mass. Several players essential in the
      maintenance of myocardial extracellular matrix homeostasis including B-type
      natriuretic peptide, matrix metalloproteinase-2, tumour necrosis factor, and
      transforming growth factor were also significantly altered by PD123319. These
      data suggest that AT2 blockade is involved in significant changes in myocardial
      extracellular matrix components translating into decreases in tissue mass in the
      salt-sensitive ANP-/- animal.

PMID- 16900248
TI  - Roles of Ca2+ and protein kinase C in the excitatory response to serotonin in
      embryonic molluscan ciliary cells.
AB  - We examined the roles of Ca2+ and protein kinase C (PKC) in the cilio-excitatory
      response to serotonin in pedal ciliary cells from Helisoma trivolvis embryos.
      Serotonin (5-hydroxytryptamine; 5-HT; 100 micromol/L) induced an increase in
      ciliary beat frequency (CBF) was abolished by microinjected BAPTA (50 mmol/L),
      but was only partially inhibited by the phospholipase C inhibitor U-73122 (10
      micromol/L). The diacylglycerol analogs 1-oleoyl-2-acetyl-sn-glycerol (100
      micromol/L) and 1,2-dioctanoyl-sn-glycerol (100 micromol/L) caused increases in
      [Ca2+]i that were smaller than those induced by serotonin. In the absence of
      extracellular Ca2+, 1,2-dioctanoyl-sn-glycerol (100 micromol/L) failed to elicit
      an increase in both CBF and [Ca2+]i. In contrast, the serotonin-induced increase
      in CBF persisted in the absence of extracellular Ca2+, although the increase in
      [Ca2+]i was abolished. PKC inhibitors bisindolylmaleimide (10 and 100 nmol/L) and
      calphostin C (10 nmol/L) partially inhibited the serotonin-induced increase in
      CBF, but didn't affect the serotonin-induced change in [Ca2+]i. These findings
      suggest that an intracellular store-dependent increase in [Ca2+]i mediates the
      cilio-excitatory response to serotonin. Furthermore, although PKC is able to
      cause an increase in [Ca2+]i through calcium influx, it contributes to the cilio
      excitatory response to 5-HT through a different mechanism.

PMID- 16900249
TI  - In vivo effect of Trigonella foenum graecum on the expression of pyruvate kinase,
      phosphoenolpyruvate carboxykinase, and distribution of glucose transporter
      (GLUT4) in alloxan-diabetic rats.
AB  - Plasma glucose levels are maintained by a precise balance between glucose
      production and its use. Liver pyruvate kinase (PK) and phosphoenolpyruvate
      carboxykinase (PEPCK), 2 key enzymes of glycolysis and gluconeogenesis,
      respectively, play a crucial role in this glucose homeostasis along with skeletal
      muscle glucose transporter (GLUT4). In the diabetic state, this balance is
      disturbed owing to the absence of insulin, the principal factor controlling this
      regulation. In the present study, alloxan-diabetic animals having high glucose
      levels of more than 300 mmol/L have been taken and the administration of
      Trigonella seed powder (TSP) to the diabetic animals was assessed for its effect
      on the expression of PK and PEPCK in liver and GLUT4 distribution in skeletal
      muscle of alloxan-diabetic rats. TSP treatment to the diabetic animals resulted
      in a marked decrease in the plasma glucose levels. Trigonella treatment partially
      restored the altered expression of PK and PEPCK. TSP treatment also corrected the
      alterations in the distribution of GLUT4 in the skeletal muscle.

PMID- 16900250
TI  - The role of diagnostic selective nerve root blocks in the management of spinal
      pain.
AB  - Biochemical mechanisms to explain pain generation began relatively recently.
      Evaluating pain originating from the spine can be challenging because no
      historical or physical examination findings are sufficiently sensitive or
      specific for identifying each of the myriad of potential pain generators. These
      discrete anatomic structures include the nerve root, disc annulus, posterior
      longitudinal ligament, sacroiliac joint, and facet joint. The diagnostic
      selective nerve root block is a useful test to determine the etiology of pain
      when other testing is inconclusive. If a patient with radicular symptoms has non
      corroborative visual anatomic and neurophysiologic testing, diagnostic selective
      nerve root block may elucidate the level of pain generation. Also, in a patient
      with multiple abnormalities on visual anatomic testing, the lesion of clinical
      significance can be identified. However, this test may not be necessary in the
      patient when the specific radiculopathy level diagnosis is apparent; this is the
      case when a characteristic history and physical examination have a corroborative
      single-level imaging lesion. Determining which level is generating symptoms has
      implications for subsequent physical therapy, therapeutic injections, and
      surgery. This review of selective nerve root blocks describes the relevant
      anatomy, pathophysiology, rationale, clinical utility, and complications.

PMID- 16900252
TI  - Spinal endoscopy and lysis of epidural adhesions in the management of chronic low
      back pain.
AB  - Spinal endoscopy with epidural adhesiolysis is an interventional pain management
      technique which emerged during the 1990s. It is an invasive but important
      treatment modality in managing chronic low back pain that is nonresponsive to
      other modalities of treatment, including percutaneous spring guided adhesiolysis
      and transforaminal epidural injections. While epidural adhesions most commonly
      result following surgical intervention of the spine, leakage of disc material
      into the epidural space following an anular tear, or an inflammatory response can
      also result in their formation. Even though advanced technology, including
      computerized tomography and magnetic resonance imaging,have made significant
      advances in the diagnosis of epidural fibrosis, it is believed that epidural
      adhesions resulting in chronic persistent pain are poorly managed. Percutaneous
      endoscopic lysis of epidural scar tissue has been shown to be cost effective and
      a safe modality. This review discusses various aspects of endoscopic
      adhesiolysis, including clinical effectiveness, complications, rationale, and
      indications.

PMID- 16900251
TI  - Provocative discography in low back pain patients with or without somatization
      disorder: a randomized prospective evaluation.
AB  - Recent reports of provocative discography not only instill confusion, but also
      create numerous questions about its value in evaluating low back pain. It was
      reported that provocative discography produced pain in patients who were not
      suffering with low back pain but suffering with somatization disorder and
      depression. This study was designed to evaluate 50 randomly assigned patients,
      with 25 patients in Group I without somatization disorder and 25 patients in
      Group II with diagnosis of somatization disorder. In addition, depression,
      generalized anxiety disorder and combinations thereof were also evaluated. All
      patients underwent discography, investigating two to three discs in each patient.
      All studies included a control level with a disc that did not produce the
      patient's pain upon injection of contrast medium. Provocation with exact pain
      reproduction concordant with the symptom complex upon injection of contrast into
      the disc was considered positive. Any other response, with or without pain, was
      considered negative. Results showed positive provocative discography in 46% of
      the patients in the somatization group compared to 54% in the non-somatization
      group; in 46% of patients with depression compared to 54% of patients without
      depression; in 15 of 30 patients with generalized anxiety disorder; in 11 of 20
      patients without generalized anxiety disorder; and in 42% of patients with
      combined somatization and depression, with negative discography in 58% of the
      patients. It is concluded that provocative discography provides similar results
      in patients with or without somatization, with or without depression, with
      somatization but with or without depression or with other combinations of the
      psychological triad of somatization disorder, depression, and generalized anxiety
      disorder.

PMID- 16900253
TI  - Evaluation of the role of facet joints in persistent low back pain in obesity: a
      controlled, prospective, comparative evaluation.
AB  - Chronic low back pain and obesity are two common medical conditions. Obesity has
      been associated with symptoms such as adverse fat distribution and multiple
      secondary disorders, including low back pain. Obesity is defined as being 30%
      over ideal weight, which influences normal body mechanics as well as recovery
      from an injury. Facet joints have been described as contributing to a significant
      proportion of patients suffering with persistent or chronic low back pain,
      variably from 15% to 45%. Since an obese patient is at a higher risk of
      disability compared to a patient with normal weight, obesity has been described
      as a confounding factor in persistent low back pain. This study included 100
      patients, with 50 patients in Group I who were of normal weight and 50 patients
      in group II who were obese, by random allocation. Facet joints were investigated
      with diagnostic blocks using lidocaine 1% initially, followed by bupivacaine
      0.25%. The results showed that the prevalence rate of facet joint pain in chronic
      low back pain in Group I or nonobese patients was 36%, in contrast to 40% in
      Group II, or the obese patient group, with no significant differences among the
      two groups. The study also showed a false-positive rate of 39% in the total
      sample, or 44% in Group I nonobese patients and 33% in Group II, or obese
      patients. It is concluded that the prevalence of lumbar facet joint mediated pain
      of 40% in obese patients and 36% in patients of normal weight with a false
      positive rate of 33% in obese patients and 44% in nonobese patients is similar to
      the results of multiple previous studies concluding that facet joint mediated
      pain is a common occurrence in obese patients; however, the incidence of facet
      joint mediated pain is similar in obese patients and nonobese patients.

PMID- 16900254
TI  - Transforaminal ventral epidural adhesiolysis.
AB  - Epidural fibrosis with chronic low back pain, nonresponsive to traditional
      measures of treatment including surgery, is a common entity in modern medicine.
      Traditionally, epidural steroid injections have been employed to treat chronic
      low back pain and radiculopathy associated with failed back surgery. Due to the
      poor effectiveness of epidural steroid injections in post lumbar laminectomy
      syndrome, epidural adhesiolysis was introduced in the early 1980s. Caudal
      epidural adhesiolysis with hypertonic saline neurolysis has been described
      extensively in the literature and has been proven to be relatively successful and
      safe. To improve the results and reach the target area with steroid,
      transforaminal ventral epidural adhesiolysis has been utilized. This
      retrospective case analysis included 14 patients. Transforaminal ventral epidural
      adhesiolysis was performed on an outpatient basis in all patients. The results
      showed 93% improvement initially, which decreased to 71% at 1 month, 57% at 3
      months, 43% at 6 months and 21% at 1 year. The results of this case study show
      that ventral epidural lysis of adhesions with hypertonic saline neurolysis is
      safe and effective in managing chronic low back and lower extremity pain in
      patients who failed to respond to other conservative modalities of treatments,
      including fluoroscopically directed transforaminal epidural steroid injections.

PMID- 16900255
TI  - HIPPA privacy regulations: practical information for physicians.
AB  - After much debate and controversy, the Bush administration announced on April 12,
      2001, that it would implement the Health Insurance Portability and Accountability
      Act (HIPAA) privacy regulations issued by the Clinton administration in December
      of 2000. The privacy regulations became effective on April 14, 2001. Although the
      regulations are considered final, the Secretary of the Department of Health and
      Human Services has the power to modify the regulations at any time during the
      first year of implementation. These regulations affect how a patient's health
      information is used and disclosed, as well as how patients are informed of their
      privacy rights. As "covered entities," physicians have until April 14, 2003, to
      comply fully with the HIPAA privacy regulations, which are more than 1,500 pages
      in length. This article presents a basic overview of the new and complex
      regulations and highlights practical information about physicians' compliance
      with the regulations. However, this summary of the HIPAA privacy regulations
      should not be construed as legal advice or an opinion on specific situations.
      Please consult an attorney concerning your compliance with HIPAA and the
      regulations promulgated thereunder.

PMID- 16900256
TI  - Effect of sedation on validity of diagnostic facet joint injections.

PMID- 16900257
TI  - Re: Interventional Techniques in the Management of Chronic Pain: Part 2.0.

PMID- 16900258
TI  - Algorithms for interventional techniques in chronic pain.

PMID- 16900259
TI  - Sacroiliac joint syndrome.

PMID- 16900260
TI  - Direct application of plasmid DNA containing type I interferon transgenes to
      vaginal mucosa inhibits HSV-2 mediated mortality.
AB  - The application of naked DNA containing type I interferon (IFN) transgenes is a
      promising potential therapeutic approach for controlling chronic viral
      infections. Herein, we detail the application of this approach that has been
      extensively used to restrain ocular HSV-1 infection, for antagonizing vaginal HSV
      2 infection. We show that application of IFN-alpha1, -alpha5, and -beta
      transgenes to vaginal mouse lumen 24 hours prior to HSV-2 infection reduces HSV-2
      mediated mortality by 2.5 to 3-fold. However, other type I IFN transgenes (IFN-
      alpha4, -alpha5, -alpha6, and -alpha9) are non effectual against HSV-2. We
      further show that the efficacy of IFN-alpha1 transgene treatment is independent
      of CD4+ T lymphocytes. However, in mice depleted of CD8+ T lymphocytes, the
      ability of IFN-alpha1 transgene treatment to antagonize HSV-2 was lost.

PMID- 16900262
TI  - Poverty, Socioeconomic Change, Institutional Anomie, and Homicide.
AB  - Objective. This study examined institutional anomie theory in the context of
      transitional Russia. Methods. We employed an index of negative socioeconomic
      change and measures of family, education, and polity to test the hypothesis that
      institutional strength conditions the effects of poverty and socioeconomic change
      on homicide rates. Results. As expected, the results of models estimated using
      negative binomial regression show direct positive effects of poverty and
      socioeconomic change and direct negative effects of family strength and polity on
      regional homicide rates. There was no support, however, for the hypothesis that
      stronger social institutions reduce the effects of poverty and socioeconomic
      change on violence. Conclusions. We interpret these results in the Russia
      specific setting, concluding that Russia is a rich laboratory for examining the
      effects of social change on crime and that empirical research in other nations is
      important when assessing the generalizability of theories developed to explain
      crime and violence in the United States.

PMID- 16900261
TI  - Cryomacroscopy of vitrification, Part II: Experimental observations and analysis
      of fracture formation in vitrified VS55 and DP6.
AB  - A new imaging device, termed a "cryomacroscope", was used to observe
      macrofractures in the cryoprotectant cocktails DP6 and VS55. Details of the
      design and construction of the cryomacroscope were presented in Part I of this
      report, which focused on describing the apparatus and observations of
      crystallization. Part I and the current paper (Part II) describe events that
      occur as 1 ml of cryoprotectant contained in a glass vial is cooled from room
      temperature down to cryogenic temperatures (~ -135 degrees C). The presence of
      cracking, as well as patterns in their position and orientation, are found to be
      dependent on the cooling rate and on the specific cryoprotectant cocktail.
      Cracks, if present, disappear upon rewarming, although they appear to be sites
      for later preferential crystallization. Computations which predict temperatures
      and mechanical stresses are used to explain observations of cracking. In
      conjunction with these reports, additional photos of cryomacroscopy of
      vitrification, crystallization, and fracture formation are available at
      http://www.me.cmu.edu/faculty1/rabin/CryomacroscopyImages01.htm.

PMID- 16900263
TI  - Research Note: Patterns of Alcohol-Related Mortality in Russia.
AB  - The level of alcohol consumption in Russia is among the highest in the world and
      is often associated with a variety of problems in the country. Until recently,
      however, it was impossible to examine the health and social burdens associated
      with consumption in Russia due to Soviet secrecy surrounding vital statistics and
      health data related to alcohol and other topics. This study employed newly
      available mortality data to describe the demographic, temporal, and spatial
      patterns of mortality resulting directly from chronic and acute alcohol
      consumption in the country. The data reveal that in spite of high overall rates
      of alcohol-related mortality in Russia, levels of mortality vary considerably
      along these dimensions. Although descriptive in nature, the patterns of alcohol
      related mortality in Russia presented here should provide initial observations
      with which to generate and test hypotheses concerning the causes and consequences
      of these patterns.

PMID- 16900264
TI  - Health and social care in aging population: an integrated care institution for
      the elderly in Greece.
AB  - PURPOSE: To describe the nature of the services actually offered to the elderly
      in Greece by an institution of integrated care, as opposed to those that should
      be offered according to the relevant law, and to investigate the factors
      influencing the supply of those services. BACKGROUND: By the year 2020 about 20
      million people will be aged 80 and over in the European Union. People of third
      age consist 16.9% of the total Greek population. Population aging has major
      implications on health services, employment and society as a whole. "Open Care
      Centres for the Elderly" (KAPI) is a rapidly developing and expanding institution
      providing integrated care for the elderly. METHODS: A questionnaire to be
      completed by the staff was sent to all 370 KAPI. Response rate reached 66%. For
      the analysis of the data multiple logistic regression analysis was performed
      using SPSS 10.0. RESULTS: Both medical and social care is provided by the KAPI to
      the elderly with different magnitude all over the country. Factors such as number
      of members, medical, paramedical and non-medical staff and fund availability in
      the KAPI mainly influence the supply of services. CONCLUSIONS: Integrated care
      services are offered by the KAPI. However, more steps need to be taken towards
      the direction of other European countries' integrated care schemes, in order to
      improve both quality and quantity of the services provided.

PMID- 16900267
TI  - Special stains reveal unusual cells and structures in cornea.

PMID- 16900266
TI  - Early clinical use of amniotic membrane in medicine and ophthalmology.

PMID- 16900268
TI  - Tissue engineering: current and future approaches to ocular surface
      reconstruction.
AB  - Although cells have been cultured outside the body for many years, research has
      only recently begun to develop complex three-dimensional tissue constructs that
      will, ideally, mature into fully functional tissues and organs. Tissue
      engineering is an emerging field in the area of biotechnology that combines the
      principles and methods of life sciences with those of engineering for the purpose
      of regenerating, repairing, or replacing diseased tissues. In this review, we
      describe the recent advances and current development of tissue engineering
      approaches as related to the ocular surface system, which comprises the three
      main integrated tissue units: conjunctiva, cornea and lacrimal glands.

PMID- 16900269
TI  - Patient-reported symptoms in dry dye disease.
AB  - Clinically, dry eye has often been reported as a "symptom-based" disease, and
      definitions of dry eye based on symptoms have been used to define dry eye
      prevalence in population-based studies. Given this, patient-reported symptoms
      often do not correlate with diagnostic tests unless disease is severe or testing
      is tightly controlled. Progress in the understanding of dry eye symptoms has been
      made over the last 10 years; however, the link between symptoms and disease
      status, such as ocular surface damage or inflammation, remains elusive. Although
      several surveys for dry eye have been developed for screening or diagnosis, an
      accepted, validated survey capable of accurately monitoring changes with time or
      treatment is not available. Common symptoms, available surveys, and the
      associations between diagnostic tests and symptoms are reviewed.

PMID- 16900270
TI  - Ocular surface sealants and adhesives.
AB  - Tissue adhesives, both synthetic and biologic, have a long history of use in
      ophthalmology. Cyanoacrylate-based glues have traditionally been the most widely
      used glues for various purposes. They have been specially useful for treating
      corneal perforations and have had significantly improved long-term outcomes. More
      recently, fibrin-based glues have gained a major role as a suture substitute for
      attaching biologic tissues and as surface sealants. The literature supports
      expanded use of fibrin glue in this fashion. Other new agents, such as
      polyethyelene glycols, have been underutilized and hold promise, especially as
      surface protectants. Numerous other glues are being developed and show promise as
      ocular surface sealants and protective membranes. Advances in knowledge about
      tissue adhesives are leading to more effective and efficient ophthalmic care.

PMID- 16900273
TI  - Bio-generics.

PMID- 16900272
TI  - Utility assessment to measure the impact of dry eye disease.
AB  - Utility assessment is a formal method for quantifying and understanding the
      relative impact of a given health state or disease on patients. In this article,
      methodology of utility assessment is explained and illustrated, and results of an
      original study are reported. The study was conducted to determine utility values
      (patient preferences) associated with dry eye disease and compare them to other
      disease utilities, as well as to compare patient and physician assessments of
      disease. Forty-four patients in the United Kingdom with moderate to severe dry
      eye were surveyed via interactive utility assessment software. Utility values
      were measured by the Time Trade-Off (TTO) and Standard Gamble (SG) methods and
      adjusted to scores from 1.0=perfect health to 0.0=death. Patients reported
      utilities for: self-reported current dry eye status, self-reported current
      comorbidities, various dry eye severities, and binocular and monocular painful
      blindness. Patient's dry eye severity was independently classified by patient and
      physician assessments. Correlation analyses (Pearson) were performed between
      patients' current dry eye utilities and the physician-assessed severity.
      Agreement between self-reported and physician-reported patient severity was
      analyzed (Kappa). Patients reported higher utilities for their current dry eye
      condition than for monocular and binocular blindness (SG:0.84>0.60>0.51;
      TTO:0.67>0.43>0.38). Using TTO, the mean score for asymptomatic dry eye (0.68)
      was similar to that for "some physical and role limitations with occasional pain"
      and severe dry eye requiring surgery scored (0.56) similarly to hospital dialysis
      (0.56-0.59) and severe angina (0.5). Utilities described for scenarios of dry eye
      severity levels were slightly higher for patients self-reported as mild-to
      moderate versus those self-reported as severe. For current dry eye condition,
      mean utilities for these groups were 0.72 for self-reported mild-to-moderate and
      0.61 for self-reported severe. Utilities for dry eye were in the range of
      conditions accepted as lowering health utilities. Severe dry eye utilities were
      similar to those reported for dialysis and severe angina, highlighting the impact
      of dry eye disease on patients.

PMID- 16900274
TI  - James V. Aquavella, MD.

PMID- 16900275
TI  - Impacts of HIV infection and HAART use on quality of life.
AB  - BACKGROUND: Studies have shown the detrimental effect of HIV disease on quality
      of life (QOL). Changes in QOL related to the use of highly active antiretroviral
      therapy (HAART) have been inconsistent and it is unknown how QOL after HAART
      compares to pre-infection levels. OBJECTIVE: The objective of this study was to
      determine the impacts of becoming HIV infected and using HAART on QOL within
      individuals followed in the Multicenter AIDS Cohort Study (MACS). METHODS: Using
      the standard Medical Outcome Study SF-36 form, QOL data were collected pre
      seroconversion, post-seroconversion but before HAART initiation, and after HAART
      initiation for 68 seroconverters. The QOL physical health summary score (PHS) and
      mental health summary score (MHS) were used as outcomes. The effects of HIV
      infection and HAART use on QOL summary scores were determined using random
      effects mixed linear models after controlling for possible confounders. The
      clinical significance of QOL change was assessed using the Cohen's effect size
      method. RESULTS: Compared to pre-seroconversion values, the PHS decreased after
      seroconversion (mean difference (diff)=-1.62; 95% confidence interval (CI): [
      3.20, -0.03]) and after HAART initiation (diff=-4.20; 95% CI: [-5.86, -2.54])
      with small to medium effect sizes. The score remained significantly lower than
      prior to HIV infection (diff=-6.16; 95% CI: [-8.09, -4.23]) after being on HAART
      for more than 4 years. The MHS did not significantly differ upon seroconversion
      (diff=-1.16; 95% CI: [-3.32, 1.00]). After using HAART for more than 4 years, the
      MHS was significantly greater than prior to HIV infection (diff=2.93; 95% CI:
      [0.31, 5.55]) with a small effect size. CONCLUSION: The QOL of participants has
      been dynamic over the HIV disease course. HIV infection deteriorated physical but
      not mental QOL. In this group, although the PHS following HAART has remained
      lower than that prior to infection, HAART has enhanced mental health functioning.

PMID- 16900276
TI  - Changes in symptoms and health-related quality of life in a nationally
      representative sample of adults in treatment for HIV.
AB  - Patient-centered measures of functioning and well-being are needed to monitor and
      improve health for HIV-infected persons. We estimated the associations between
      HRQOL and symptoms over time in HIV-infected persons, adjusting for demographic
      and clinical characteristics using a longitudinal study of a nationally
      representative cohort of 2267 patients in care for HIV infection surveyed in 1996
      and again in 1998. We used two global measures of HRQOL (overall health and
      overall quality of life) scored to have a mean of 50 and standard deviation of 10
      in the sample. The total number of symptoms decreased (-1.29, p<0.001 for the
      difference), and overall health (1.09, p<0.001 for the difference) and overall
      quality of life (1.31, p<0.001 for the difference) improved over the period.
      Controlling for baseline symptoms and HRQOL, each additional symptom at follow-up
      (B=-1.14, p<0.001) was associated with worsened overall health and worsened
      overall quality of life (B=-0.95, p<0.001). The association of two additional
      symptoms with lower global HRQOL was similar in magnitude to the effect of having
      significant depressive symptoms or the diagnosis of AIDS. In conclusion, among
      HIV-infected patients, symptoms are significantly related to HRQOL over time. The
      functioning and well-being of patients with HIV is inextricably linked to the
      symptoms they experience.

PMID- 16900277
TI  - Low health-related quality of life among abused women.
AB  - In a cross-sectional study, we sent a self-administered questionnaire to all the
      women's shelters in Norway to describe health-related quality of life among women
      who had experienced violence from an intimate partner. Every woman who could
      understand Norwegian and was staying at a women's shelter in Norway for more than
      1 week from October 2002 to May 2003 was asked to participate. We described
      violence by intimate partners by using the Severity of Violence against Women
      Scale and the Psychological Maltreatment of Women Index. We used the SF-36 Health
      Survey to measure health-related quality of life. These women experienced a
      multitude of threats and actual physical and psychological violence during their
      partnership. Their health-related quality of life was low and significantly
      (p<0.001) below the norm for the female population of Norway in all dimensions.
      The SF-36 mental health dimension was 2.5 standard deviations below the norm.
      Women at women's shelters in Norway who had experienced domestic violence had
      very low and clinically significantly reduced health-related quality of life
      scores. Health care workers must give priority to developing intervention plans
      for victims of violence from intimate partners.

PMID- 16900278
TI  - Patient experiences with information in a hospital setting: associations with
      coping and self-rated health in chronic illness.
AB  - The structural relations between patient experiences with information provided by
      hospital staff, coping behaviour and changes in self-rated health were studied in
      a cohort of people with chronic illness (n=556) over a period of 2 years. A
      structural equation approach was applied to model cross-sectional and
      longitudinal effects. Positive experiences with information were cross
      sectionally but not longitudinally associated with improved self-rated health.
      Patient experiences with information are not related to avoidance coping, but
      positive experiences contribute to more frequent use of supportant coping. The
      findings in the present study indicate that measures of patient experiences with
      information are not merely a reflection of patients' health or coping behaviour.
      More theoretical work is required to describe the relationships between different
      patient reported outcomes. The insight into mechanisms underlying changes in
      physical and mental health in chronic illness could be further improved by
      evaluating the effects of specific educational and psychosocial interventions in
      a longitudinal design.

PMID- 16900279
TI  - Social participation and employment status after kidney transplantation: a
      systematic review.
AB  - OBJECTIVE: To summarize and assess literature regarding social participation of
      recipients after successful kidney transplantation. METHODS: A systematic review
      including a literature search in Medline (1980-2003) and five other databases,
      and assessment of methodological quality of selected studies by two reviewers
      applying a checklist of twelve criteria. RESULTS: Seventeen studies out of 1443
      identified references were selected. Quality scores for internal validity ranged
      from 0% to 50% (median 20%). Employment was the most used indicator of social
      participation and two studies briefly reported on vacation and recreation.
      Employment rate ranged from 18% to 82%, however differences in defining
      categories of employment or lack of description were present. Study populations
      were heterogeneous with regard to demographic and clinical characteristics. Three
      studies identified pre-transplant employment status as predictor of post
      transplant employment. Other potential risk factors were not consistent across
      studies. CONCLUSION: Measurement of social participation focuses mainly on
      employment status. Quality assessment revealed shortcomings in reporting and
      validity of studies, whereby valid conclusions regarding the degree of social
      participation after kidney transplantation cannot be drawn. Future research
      should supplement the focus on employment status by examining other aspects of
      social participation as well as potential risk factors.

PMID- 16900280
TI  - Understanding global transition assessments.
AB  - OBJECTIVE: Several methods currently used for determining meaningful or important
      change in health-related quality of life (HRQoL) measures are anchored by global
      transition items. It can be empirically demonstrated that patients' responses to
      these gold standards for change do not adequately incorporate the prior
      condition, yet these transition items play an influential role in patient
      clinician communications and cannot be disregarded. This follow-up study queried
      patients to better understand how they ascertained their transition assessments.
      DATA SOURCE: Prior to their qualitative interviews, the 41 participants in this
      study had completed 1 year of enrollment in a clinical study with bi-monthly
      HRQoL telephone interviews that included the SF-36 and a disease-specific HRQoL
      instrument (asthma, COPD, or heart disease), as well as global transition
      assessments for each instruments domains. STUDY DESIGN: We used face-to-face
      cognitive interview and the think aloud approaches to obtain qualitative clues
      for understanding patient reports of HRQoL changes over time. Interview
      transcripts were coded using the four components of the Rapkin-Schwarz Appraisal
      Model: frame of reference; sampling strategy; standards of comparison; and
      combinatory algorithm. PRINCIPAL FINDINGS: Patients' explanations for determining
      global transition item responses often focused on current mobility and fatigue
      patterns, physicians' statements about their conditions, comparisons of their
      current states with the prior health conditions, and strong personal convictions
      that reflected a resistance to voicing any emotional changes. Patients also
      expressed primary health concerns, like back pain, that were not related to the
      chronic conditions (asthma, COPD or heart disease) under investigation.
      CONCLUSIONS: HRQoL studies and patient-clinician communications that incorporate
      global transition assessments to anchor the interpretations of HRQoL changes
      should also consider additional relevant questions to understand the process
      patients uses to appraise and report changes in HRQoL.

PMID- 16900281
TI  - The CarerQol instrument: a new instrument to measure care-related quality of life
      of informal caregivers for use in economic evaluations.
AB  - The societal perspective in economic evaluations dictates that costs and effects
      of informal care are included in the analyses. However, this incorporation
      depends on practically applicable, reliable and valid methods to register the
      impact of informal care. This paper presents the conceptualisation and a first
      test of the CarerQol instrument, aimed at measuring care-related quality of life
      in informal caregivers. The instrument combines the information density of a
      burden instrument (encompassing seven important burden dimensions) with a
      valuation component (a VAS scale for happiness). The instrument was tested in a
      Dutch sample of heterogeneous caregivers (n=175) approached through regional
      caregiver support centres. This first test describes the feasibility as well as
      convergent and clinical validity of the CarerQol instrument. The seven burden
      dimensions related well with differences in VAS scores. In all instances, the
      average CarerQol-VAS scores decreased as the severity of problems increased.
      Multivariate analyses showed that the seven burden dimensions explained 37-43% of
      the variation in CarerQol-VAS scores, depending on the model used. The CarerQol
      seems a promising new instrument to register the impact of informal caregivers in
      economic evaluations.

PMID- 16900282
TI  - Associations between a functional independence measure (WeeFIM) and the pediatric
      quality of life inventory (PedsQL4.0) in young children with physical
      disabilities.
AB  - OBJECTIVES: To determine the association between functional status, measured by
      the WeeFIM and health-related quality of life (HRQL), measured by the PedsQL4.0
      for children with physical disabilities. To explore child, parent and service
      related factors associated with each of these measures. PATIENTS: Parents of 115
      children (2-5 years) with physical disabilities who were referred to occupational
      (OT) or physical therapy (PT). Mean age of the children was 3 years 7 months (+/
      10 months), 79 were boys and 67 were diagnosed with global developmental delay.
      RESULTS: Children had more difficulties with self-care tasks and cognitive
      abilities, as compared to mobility activities on the WeeFIM. The correlation
      between total WeeFIM and total PedsQL4.0 was r=0.39. WeeFIM mobility and self
      care quotients were each fairly correlated with PedsQL-Physical Health Summary
      Score (rs=0.29 and rs=0.28 respectively). There was no significant association
      between WeeFIM cognition quotient and each of PedsQL scores (rs=0.03-0.05). The
      receipt of PT services was highly associated (p<0.001) with lower scores on the
      PedsQL-Physical Health Summary score, PedsQL-Total score, and WeeFIM mobility
      quotient. CONCLUSION: The WeeFIM and the PedsQL4.0 appear to assess related but
      different constructs, supporting the need to incorporate complementary measures
      when measuring general health of children with disabilities.

PMID- 16900284
TI  - Validation of the genital herpes treatment satisfaction questionnaire (GHerpTSQ)
      in status and change versions.
AB  - A new measure of treatment satisfaction (GHerpTSQ) for recurrent genital herpes
      simplex virus (HSV) was validated and used to evaluate two therapeutic strategies
      widely used for the management of HSV: episodic treatment, where individual
      herpes outbreaks are treated as they arise; suppressive therapy, where treatment
      is taken daily to prevent HSV outbreaks. Satisfaction with treatment is important
      since daily dosing with suppressive therapy is necessary in the absence of
      symptoms. A 12-item questionnaire was designed using a modified form of the
      Diabetes treatment satisfaction questionnaire (DTSQ). The psychometric properties
      of the GHerpTSQ were evaluated within a sample of 125 Canadians with a history of
      HSV (type 1, 2) infection participating in a 48 week randomised cross-over trial.
      Factor analysis suggested that the items can be analysed as two separate
      subscales corresponding to Control/effectiveness, and Convenience/lifestyle; the
      single item concerning side effects was retained for separate analysis. Forced
      one-factor analysis showed that the two subscales can be combined to obtain a
      total score relating to overall treatment satisfaction. The GHerpTSQ has good
      internal reliability, clear structure with little overlap of subscales and
      evidence of good sensitivity to changes in treatment.

PMID- 16900283
TI  - Parent and health professional perspectives in the management of adolescents with
      diabetes: development of assessment instruments for international studies.
AB  - OBJECTIVE: Assessment of quality of life (QOL) in adolescents with diabetes
      requires patient, parent and health professional input. Psychometrically robust
      instruments to assess parent and professional perspectives are required. RESEARCH
      DESIGN AND METHODS: Questionnaires concerning adolescent QOL were developed for
      completion by parents and health professionals. In an international study
      assessing QOL in 2,101 adolescents with diabetes (median age 14 years, range 10
      18; from 17 countries including Europe, Japan and North America), parents and
      health professionals completed their respective questionnaires between March and
      August 1998. RESULTS: Feasibility and acceptability of the new questionnaires
      were indicated by high questionnaire completion rates (adolescents 92%; parents
      89%; health professionals 94%). Internal consistency was confirmed (Cronbach's
      alpha coefficients 0.80 parent; 0.86 health professional). Correlations of
      Diabetes Quality of Life Questionnaire for Youths (DQOLY) scores with parent and
      health professional global QOL ratings were generally low (r ranging from 0.12 to
      0.36). Parent-rated burden decreased incrementally across adolescence,
      particularly for girls. Professional-rated burden followed a similar profile but
      only after age 15 years. Until then, burden was rated as uniformly high.
      Clinically relevant discrepancies in parent and professional burden scores were
      noted for one-parent families and families where adolescents had been referred
      for psychological help. In both cases, health professionals but not one-parent
      families perceived these as high burden situations. The clinical significance of
      this relates to the significantly poorer metabolic control recorded for
      adolescents in both situations. CONCLUSIONS: Parent and health professional
      questionnaires were found to have adequate internal consistency, and convergent
      and discriminant validity in relation to key clinical and QOL outcomes. The
      questionnaires are brief, easy to administer and score. They may also enable
      comparisons across countries and languages to facilitate development of
      international health outcome parameters. The inclusion of the parent and health
      professional perspectives completes a comprehensive assessment of adolescent QOL
      relevant to diabetes.

PMID- 16900285
TI  - A measure of quality of life after abdominal surgery.
AB  - OBJECTIVE: To develop a reliable and valid measure of short-term quality of life
      after abdominal surgery. SUMMARY BACKGROUND DATA: A major limitation of clinical
      trials evaluating laparoscopic surgical procedures has been the lack of a measure
      of short-term quality of life after abdominal surgery. METHODS: We used existing
      health status measures, focus groups, and semi-structured patient interviews to
      generate a prototype questionnaire of 51 items, which was administered to
      patients within 2 weeks after an abdominal surgical procedure. We used structural
      equations modeling to reduce the number of items, retaining the three items with
      the highest factor loadings on each of the factors that accounted for one or more
      eigenvalue. RESULTS: We administered the prototype questionnaire to 500 patients
      (mean age [SD] 53.4 [16.0], 51.4% male, 73.0% inpatient) at a mean 4.1 days after
      an abdominal surgical procedure. Item reduction yielded an 18-item measure with 6
      sub-scales. The final instrument demonstrated good model fit in relation to our
      hypothesized factors (root mean square error of approximation 0.085, goodness-of
      fit index 0.89). CONCLUSIONS: We developed a reliable and valid 18-item, 6
      subscale measure of health-related quality of life after abdominal surgery, for
      use as an outcome measure in studies comparing laparoscopic and conventional
      abdominal surgery.

PMID- 16900286
TI  - Cross-cultural validation of the Decisional Conflict Scale in a sample of French
      patients.
AB  - INTRODUCTION: The Decisional Conflict Scale (DCS, 16 items, 5 dimensions)
      designed to measure the level of decisional conflict experienced by patients
      making health care decisions has not yet been validated in French. METHODS: A
      national sample of French cancer patients (n=644) facing the decision to undergo
      BRCA genetic testing was tested for this purpose, including a control group and
      an experimental group who had received an information booklet. Reliability and
      criterion validity were investigated. To check the validity of the factors
      selected, an exploratory factor analysis was then conducted, followed by
      confirmatory factor analyses. RESULTS: Reliability was satisfactory
      (alpha=0.913). Women who definitely wanted to undergo genetic testing showed
      significantly lower DCS scores than uncertain women (p<0.001). Exploratory factor
      analysis suggested an optimal 4-dimensional model. In the control group,
      confirmatory factor analyses showed that the French model was more accurate than
      the original one. When the decision-making conflicts decreased (in the
      experimental group), both models yielded only fairly accurate indices.
      CONCLUSION: The French version of the DCS was found to give a reliable overall
      score. However, special care should be taken when using the individual subscores.
      In addition, it is necessary to take into account the context in which the
      decision-making occurs.

PMID- 16900287
TI  - Responsiveness of the coronary revascularisation outcome questionnaire compared
      with the SF-36 and Seattle Angina Questionnaire.
AB  - We describe a comparison of the responsiveness of three validated instruments
      when used with patients undergoing coronary bypass surgery (CABG) and angioplasty
      (PTCA). Patients were randomly selected to receive the Coronary Revascularisation
      Outcome Questionnaire (CROQ), and either the Seattle Angina Questionnaire (SAQ),
      or the SF-36 before and 3 months after coronary revascularisation. At total of
      199 patients (127 CABG, 72 PTCA) completed the CROQ; 55/72 CABG and 34/38 PTCA
      patients also completed the SAQ or SF-36, respectively. Effect sizes and
      standardised response means were calculated as change over the 3-month period for
      scales measuring similar constructs on each instrument. We used bootstrap
      estimation to derive 95% confidence intervals for differences in the
      responsiveness indices. For CABG, the CROQ demonstrated significantly greater
      change in psychosocial functioning than the SF-36, but less than the SAQ. For
      PTCA, the CROQ showed greater change for symptoms than the SAQ, but the SAQ was
      more responsive in terms of physical functioning; and the CROQ showed
      significantly greater change than the SF-36 for psychosocial functioning. There
      were no other significant differences between similar scales on the three
      instruments. In conclusion, the CROQ was as responsive as the disease-specific
      SAQ and more responsive than the generic SF-36.

PMID- 16900288
TI  - Validation of a Chinese version of the Medical Outcomes Study HIV Health Survey
      (MOS-HIV) among Chinese people living with HIV/AIDS in Hong Kong.
AB  - OBJECTIVES: To evaluate the Chinese version of the 35-item Medical Outcomes Study
      HIV Health Survey (MOS-HIV) in Chinese people living with HIV/AIDS (PLWHA).
      METHODS: A cross-sectional survey of 242 ethnic Chinese PLWHA in Hong Kong was
      conducted. RESULTS: Cronbach's alphas of the eight multi-item scales of the MOS
      HIV ranged from 0.78 to 0.90. Item-total and inter-scale correlation coefficients
      were acceptable. Factor analysis of the MOS-HIV identified two factors (Mental
      Health Summary scores and Physical Health Summary scores, or MHS and PHS),
      accounting for 63% total variance. The PHS and MHS correlated significantly with
      the WHOQOL-BREF(HK) and the three sub-scales of Profile of Mood States used in
      this study. Both PHS and MHS were significantly associated with self-perceived
      change in health status. PHS but not MHS was associated with Karnofsky
      Performance Status scores. PHS was also associated with disease stage. The MOS
      HIV however, did not distinguish between groups of different CD4 cell counts. It
      is likely that the quality of life of these PLWHA of different disease stages was
      good in general. CONCLUSIONS: There is a large demand for evaluating treatments
      and services programs offered to PLWHA in China. The validated Chinese MOS-HIV
      would facilitate such research activities.

PMID- 16900289
TI  - Conceptual equivalence and health-related quality of life: an exploratory study
      in Japanese and Dutch cancer patients.
AB  - Research into the equivalence of Western and Japanese conceptualizations of
      health-related quality of life (HR-QOL) is scarce. We used the Western (European
      Organization for Research and Treatment of Cancer, EORTC-QLQ-C30) and the
      Japanese (HRQoL-20) questionnaire in order to analyze the conceptual similarity
      of HR-QOL factors, and the associations between specific symptom items with
      overall HR-QOL in Japanese (n=265) and Dutch (n=174) patients with various types
      of cancer. Both populations completed both instruments. In both patient groups,
      the overall health scale of the EORTC-QLQ-C30 correlated highly (r=0.59; p<0.001)
      with the HRQOL-20 composite average score, indicating substantial conceptual
      comparability. Relationships between all EORTC-QLQ-C30 symptom items with HR-QOL
      were examined by ranking their correlations with the two overall measures of HR
      QOL. Comparable patterns in the Japanese and Dutch samples were observed. The
      results suggest a considerable conceptual equivalence of HR-QOL in Japanese and
      Dutch cancer patients, and indicate a satisfactory structural and cross-cultural
      equivalence for the EORTC-QLQ-C30 with regard to items measuring functioning and
      specific symptoms. Longitudinal studies are needed to examine the impact of
      specific symptoms on general quality of life.

PMID- 16900290
TI  - Comparing translations of the EORTC QLQ-C30 using differential item functioning
      analyses.
AB  - The European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 is
      one of the most widely used quality of life instruments for cancer patients. The
      aim of this study was to assess whether there were linguistic differences in the
      way an international sample answered the EORTC QLQ-C30 questionnaire. Thirteen
      translations of the EORTC QLQ-C30, representing 22 countries, were investigated
      using a database of 27,891 respondents, incorporating 103 separate studies.
      Differential item functioning (DIF) analyses were conducted using logistic
      regression to identify items which, after controlling for subscale, were answered
      differently by language of administration. Both uniform and non-uniform DIF were
      assessed. Although most languages showed similar results to English, at least one
      instance of statistically significant DIF was identified for each translation,
      and a few of these differences were large. In some cases, the patterns were
      supported by the results of qualitative interviews with bilingual people.
      Although, overall, there appeared to be good linguistic equivalence for most of
      the EORTC QLQ-C30 items, several scales showed strongly discrepant results for
      some translations. Some of these effects are large enough to impact on the
      results of clinical trials. Based on our experience in this study, we suggest
      that validation of translations of health-related quality of life instruments
      should include exploration of DIF.

PMID- 16900294
TI  - Study of AZFc partial deletion gr/gr in fertile and infertile Japanese males.
AB  - A recurrent partial azoospermia factor C (AZFc) deletion, called gr/gr, has been
      reported to be a male infertility risk factor. A specific type of Y chromosome
      observed in approximately 30% of Japanese males (haplogroup D derived at YAP+) is
      believed to have a fixed gr/gr deletion. A recent study claimed that
      spermatogenic failure is more likely in males with D Y chromosomes, because of
      the gr/gr deletion, the presence of which is not well characterized among D
      haplogroup chromosomes. We therefore decided to perform a systematic study of the
      frequency of the gr/gr deletion in the Japanese. We studied fertile and infertile
      males to investigate the possibility of different gr/gr frequencies. The
      deletions were detected by use of single tagged-sequences (STSs) and the D
      haplogroup sub-lineages typing were done by use of the biallelic markers M174,
      M64, M116.1, 12f2.2, M15, M151, and M125. Analysis of gr/gr deleted Y chromosomes
      showed that all are classified as haplogroup D2, suggesting a lineage
      association. The subtype D2b1 was most frequent among the Japanese, in control
      and infertile samples. The haplogroups D2b2, D*, and D1 were not found in any
      population group. Remarkably, we observed no statistical difference between
      haplogroup D sub-lineages of the infertile and control groups, although the
      statistical power of this study is low. This study suggests lack of significant
      evidence of increased infertility risk in haplogroup D Japanese males. We were
      also able to establish the ancestral chromosome that suffered a gr/gr deletion,
      and propose a new Y chromosome phylogeny for haplogroup D and its derivatives. In
      summary, we were able to define the frequency of gr/gr deletion in Japanese males
      and show that the gr/gr deletion was probably present in the ancestral Y
      chromosome that entered Japan at least 12,000 years ago.

PMID- 16900295
TI  - Pure de-novo 5 Mb duplication at Xp11.22-p11.23 in a male: phenotypic and
      molecular characterization.
AB  - Males with duplications within the short arm of the X chromosome are rare and
      most cases are inherited from a maternal heterozygote. Here we describe the first
      detailed characterization of a de-novo Xp duplication delineated to Xp11.22-
      >Xp11.23 in a 15-year-old male with moderate mental impairment, autistic-like
      behaviour, short stature, and mild dysmorphic features. Chromosome analysis (550
      band resolution) was normal and comparative genomic hybridization (CGH) analysis
      on metaphase spreads detected duplication on Xp11. Further characterization of
      the duplication by array CGH, FISH experiments with specific BAC probes, and
      genotyping with microsatellite markers helped to determine proximal and distal
      breakpoints giving a size of the duplication of approximately 5 Mb. As far as we
      are aware this is the first described male with isolated microduplication on
      Xp11.22-Xp11.23. Among the genes included within the duplicated region, and
      particularly those which are outside copy number polymorphisms, we discuss the
      relationship of FTSJ1, PQBP1 and HDAC6 with the clinical symptoms of our patient.

PMID- 16900296
TI  - A novel deletion mutation in CENPJ gene in a Pakistani family with autosomal
      recessive primary microcephaly.
AB  - Autosomal recessive primary microcephaly (MCPH) is a rare human genetic disorder
      in which the head circumference is reduced because of abnormality in fetal brain
      growth. To date, six loci and four genes have been identified for this condition.
      Our study of primary MCPH led to the identification of 33 Pakistani families with
      different ethnic backgrounds. Most of these families showed linkage to MCPH5
      locus on chromosome 1q31. Only one family with Pashtoon origin from a remote
      region in Pakistan linked to MCPH6 locus on chromosome 13q12.12-q12.13. Sequence
      analysis of exon 11 of CENPJ gene, located at MCPH6 locus, revealed a novel four
      base pair deletion mutation, which is predicted to be protein truncating.

PMID- 16900297
TI  - An algorithm for model construction and its applications to pharmacogenomic
      studies.
AB  - A model depicts the relationship between clinical phenotypes and genotypes on a
      set of genetic polymorphisms. After the model is constructed and validated, it
      may be used to predict clinical phenotypes such as traits of complex diseases. A
      pharmacogenomic model is used to predict the efficacies or adverse drug reactions
      of a medication. The construction of a model is a challenging task. This is
      because a single-locus polymorphism does not contain enough information to
      stratify patients in general, given the complex biological mechanisms involved.
      An exhaustive search for the correct combination of genotypes across multiple
      loci is, however, computationally infeasible. We are, thus, motivated to propose
      a novel algorithm for the construction of models using the multiple single
      nucleotide polymorphism (SNP) information in diplotype forms. This algorithm
      utilizes the techniques of genetic algorithms and Boolean algebra (GABA). The
      proposed algorithm is tested on simulated data, as well as real genotype datasets
      of chronic hepatitis C patients treated with interferon-combined therapy. A model
      for predicting the treatment efficacy is constructed and validated. The results
      showed that the proposed algorithm is very effective in deriving models
      comprising multiple SNPs.

PMID- 16900293
TI  - A tale of two citrullines--structural and functional aspects of myelin basic
      protein deimination in health and disease.
AB  - Myelin basic protein (MBP) binds to negatively charged lipids on the cytosolic
      surface of oligodendrocyte membranes and is responsible for adhesion of these
      surfaces in the multilayered myelin sheath. The pattern of extensive post
      translational modifications of MBP is dynamic during normal central nervous
      system (CNS) development and during myelin degeneration in multiple sclerosis
      (MS), affecting its interactions with the myelin membranes and with other
      molecules. In particular, the degree of deimination (or citrullination) of MBP is
      correlated with the severity of MS, and may represent a primary defect that
      precedes neurodegeneration due to autoimmune attack. That the degree of MBP
      deimination is also high in early CNS development indicates that this
      modification plays major physiological roles in myelin assembly. In this review,
      we describe the structural and functional consequences of MBP deimination in
      healthy and diseased myelin.

PMID- 16900299
TI  - Acute calcific tendinitis of the thumb in a child: a case report.
AB  - Acute calcific tendinitis is rare in hand and digit, especially in children. We
      describe a rare case of acute calcific tendinitis of the thumb [extensor pollicis
      longus (EPL) tendon] in a 10-year-old boy. Plain radiographs showed a calcium
      deposit in the EPL tendon. Conservative therapy completely resolved all symptoms
      in 1 week. The calcium deposit shown on plain radiographs became smaller and
      completely disappeared within 6 weeks.

PMID- 16900298
TI  - Haloarcula marismortui cytochrome b-561 is encoded by the narC gene in the
      dissimilatory nitrate reductase operon.
AB  - The composition of membrane-bound electron-transferring proteins from
      denitrifying cells of Haloarcula marismortui was compared with that from the
      aerobic cells. Accompanying nitrate reductase catalytic NarGH subcomplex,
      cytochrome b-561, cytochrome b-552, and halocyanin-like blue copper protein were
      induced under denitrifying conditions. Cytochrome b-561 was purified to
      homogeneity and was shown to be composed of a polypeptide with a molecular mass
      of 40 kDa. The cytochrome was autooxidizable and its redox potential was -27 mV.
      The N-terminal sequence of the cytochrome was identical to the deduced amino acid
      sequence of the narC gene product encoded in the third ORF of the nitrate
      reductase operon with a unique arrangement of ORFs. The sequence of the
      cytochrome was homologous with that of the cytochrome b subunit of respiratory
      cytochrome bc. A possibility that the cytochrome bc and the NarGH constructed a
      supercomplex was discussed.

PMID- 16900300
TI  - Tacrolimus as a reinforcement therapy for a patient with MPO-ANCA-associated
      diffuse alveolar hemorrhage.
AB  - A 67-year-old woman, suffering from continuous hemoptysis, was admitted to our
      hospital where she was managed with mechanical ventilation. Computed tomography
      of the chest demonstrated bilateral massive alveolar hemorrhage without evidence
      of infectious disease. She was diagnosed with anti-myeloperoxidase antineutrophil
      cytoplasmic antibody (MPO-ANCA)-associated diffuse alveolar hemorrhage because a
      high titer of MPO-ANCA was found in the serum. Plasmapheresis as well as
      methylprednisolone pulse therapy were initiated, followed by intravenous
      administration of cyclophosphamide. Tacrolimus was employed for the maintenance
      therapy, and the oral prednisolone dosage could successfully be tapered without
      recurrence, along with the decrement of the titer of MPO-ANCA.

PMID- 16900301
TI  - Purtscher's-like retinopathy as an initial presentation of adult-onset Still's
      disease: a case report and review of the literature.
AB  - Adult-onset Still's disease is a multisystem inflammatory disorder of unknown
      etiology and is characterized by high, spiking fever, arthritis, evanescent
      maculopapular rash, myalgia, serositis, leukocytosis, and involvement of various
      organs including the eyes. The ocular manifestations have been described
      including orbital pseudotumor, ptosis, and diplopia with orbital pain but never
      Purtscher's-like retinopathy. We describe a 21-year-old male patient with adult
      onset Still's disease who developed the Purtscher's-like retinopathy. To our
      knowledge, this is the first reported adult-onset Still's disease patient with
      Purtscher's-like retinopathy as the initial presentation.

PMID- 16900303
TI  - Genetic analysis of an ADRV-N-like novel rotavirus strain B219 detected in a
      sporadic case of adult diarrhea in Bangladesh.
AB  - An unusual human rotavirus strain B219 was detected in a stool specimen from a 65
      year old patient with diarrhea in Bangladesh during April 2002. Cloning and
      sequence analysis of five genes of the B219 strain indicated that this virus is
      genetically closely related to the ADRV-N strain, which caused an adult diarrhea
      outbreak in China, but distinct from groups A, B, and C rotaviruses known to
      cause diarrheal diseases in humans. Accordingly, rotavirus strains B219 and ADRV
      N were considered to belong to a novel group of human rotavirus, and the ADRV-N
      like novel human rotaviruses were suggested to be distributed to a geographically
      wider area.

PMID- 16900302
TI  - Minimum sample size requirements for bone density precision assessment produce
      inconsistency in clinical monitoring.
AB  - INTRODUCTION: Detection of change during bone mineral density (BMD) monitoring is
      affected by test precision. The International Society of Clinical Densitometry
      (ISCD) recommends that each center determine precision error using repeat
      measurements in 30 subjects (or an equivalent method providing 30 degrees of
      freedom). METHODS: We hypothesized that this sample size may be too small for a
      robust precision estimate, which could affect the performance of BMD monitoring
      in clinical practice. Replicate measurements of the spine and total hip (198
      spine and 193 hip scan pairs) were obtained (interval 6+/-5 days). The sample was
      randomly divided into six groups of 30 patients each. Root mean square standard
      deviation (RMS-SD in g/cm(2)) and coefficient of variation (RMS-CV in %)
      precision errors and corresponding 95% least significant change (LSC) were
      calculated for each group and the pooled sample. LSC cutoffs were applied to
      1,420 individuals from the Manitoba Bone Density Program who had follow-up
      measurements on the same instrument (interval 21+/-9 months). While the pooled
      spine RMS-SD was 0.017 and pooled hip RMS-SD was 0.009 g/cm(2), sample sizes of
      30 gave a range of RMS-SD point estimates from 0.012 to 0.021 for the spine and
      from 0.008 to 0.012 for the hip. RESULTS: When the respective LSC cutoffs were
      applied to the 1,420 follow-up scan pairs, the fraction of patients categorized
      with significant change in the spine varied from 20.7% to 46.0%; four of the six
      LSCs based upon 30 subjects gave fractions significantly different from the
      pooled LSC of 30.7%. Significant change fractions for the hip varied from 31.1%
      to 51.1%; two of the six LSCs based upon 30 subjects gave fractions significantly
      different from the pooled LSC of 40.1%. Similar results were obtained using
      relative precision errors. CONCLUSION: BMD precision studies using a sample size
      of 30 are insufficient to reliably characterize precision error or change during
      clinical monitoring.

PMID- 16900304
TI  - Social network among young adults with first-episode schizophrenia spectrum
      disorders: results from the Danish OPUS trial.
AB  - BACKGROUND: Social network has considerable impact on physical and mental health.
      Patients experiencing first-episode psychosis early in adult life may experience
      severe problems concerning development and maintenance of their social network.
      METHODS: A total of 547 first-episode psychotic patients (18-45) were randomised
      to standard or integrated treatment, (ACT, social skills training and family
      intervention), and followed up at 2 years. RESULTS: Service use or psychotic
      symptom score did not influence the social network size, measured after the first
      2 years of treatment. Small network size was associated with long duration of
      untreated psychosis (DUP), poor premorbid adjustment, male gender and severe
      negative symptoms. The number of friends at 2-year follow-up was predicted by
      age, A-level status, negative symptoms and number of friends at entry, while the
      determinants for number of family contacts were age, gender, disorganised
      dimension and family contacts at entry. CONCLUSIONS: Premorbid functioning,
      network size at entry and DUP is closely related to small social network size.
      The integrated psychosocial treatment programme was not sufficient to address
      this problem.

PMID- 16900305
TI  - Characteristics and needs of asylum seekers and refugees in contact with London
      community mental health teams: a descriptive investigation.
AB  - BACKGROUND: Asylum seekers and refugees may have substantial needs for mental
      health care, to which both pre-migration and post-migration traumas are likely to
      contribute. However, there is a paucity of data available to guide appropriate
      service development. AIMS: To ascertain numbers and describe the characteristics
      and needs of asylum seekers and refugees in contact with London Community Mental
      Health Teams (CMHTs). METHOD: Data were obtained from staff and clinical records
      regarding socio-demographic and clinical characteristics and service use.
      Camberwell Assessment of Need Short Appraisal Schedule (CANSAS) and Health of the
      Nation Outcome Scales (HoNOS) were completed. RESULTS: A total of 104 (11%) of
      the CMHT population were asylum seekers or refugees. Co-morbidity was frequent,
      and psychiatrists reported significant diagnostic uncertainty for 30%. The most
      common diagnoses were depression (50%) and post-traumatic stress disorder (PTSD)
      (41%), and just over half had a psychotic diagnosis (53%). Social isolation was
      common, levels of unmet need were high (mean of 6.8 unmet needs each using
      CANSAS) and the group used few services other than CMHTs. CONCLUSIONS: The
      combination of high levels of need and limited service use suggests a need to
      develop more effective services. High rates of diagnostic uncertainty suggest a
      need for a clearer understanding of the complex clinical syndromes afflicting
      this group.

PMID- 16900306
TI  - Implantation of a cardiac pacemaker - comparison of subjective stress and mood
      between in- and outpatients.
AB  - BACKGROUND: An increasing number of cardiac pacemaker implantations are performed
      in the outpatient setting. Studies have compared costs and complication rates of
      outpatient versus inpatient pacemaker implantations but little is known on the
      subjective experience of the procedure by patients. METHODS: Between 1999 and
      2000, patients were prospectively included at admission to a teaching hospital
      and to an outpatient clinic for elective pacemaker implantations in Cottbus,
      Germany. Perioperative stress was assessed prior to the operation as well as on
      the day after the implantation and 3-4 days later. We used three validated
      questionnaires to assess stress: the "Short Questionnaire of Current Stress", the
      "Multidimensional Mood Questionnaire", and the "List of Mood and Emotion
      Descriptors". RESULTS: A total of 138 patients were enrolled. Of those, 74
      patients (mean age: 71+/-12 years; 45% female) had an outpatient implantation
      compared to 64 patients in the hospital setting (mean age: 73+/-12 years; 53%
      female). Stress was highest immediately prior to the implantation and lowest on
      day 3-4 in both groups. Inpatients were significantly less likely to experience
      agitation compared to outpatients (P=0.002). On the other hand, outpatients
      reported a significantly higher activity level. There were no differences
      regarding any of the other dimensions between the two groups. CONCLUSION: Both in
      and outpatient cardiac pacemaker implantation are associated with increased
      preoperative stress. In both groups, however, stress decreases rapidly following
      the intervention. In the referral of patients, sociodemographic factors such as
      area of residence will probably play the key role.

PMID- 16900307
TI  - Aspirin resistance - does it clinically matter?
AB  - A variable responsiveness to acetylsalicylic acid(ASA) is a clinical reality that
      does not principally differ from variable responses to other kinds of drug
      treatment in other therapeutic fields. Two questions arise: (i) is any resulting
      "treatment failure"due to a pharmacological failure of the drug to act and (ii)
      is any reduced antiplatelet activity to ASA related to the clinical outcome oft
      he patient?Two major laboratory techniques are available to quantify platelet
      variability to ASA ex vivo: Measurement of platelet function and measurement of
      thromboxane formation. Both methods have limitations and did not yet result in a
      generally accepted definition of a pharmacological ASA "resistance".A "true"
      pharmacological resistance to ASA exists in selected groups of patients. However,
      unless more information is available,results from in vitro assays of platelet
      function should not be over-interpreted. More data from prospective trials are
      required,predominantly by measuring serum thromboxane formation which is a
      platelet-specific, ASA sensitive reaction. At this time,there is no reason to
      change there commended daily maintenance dose of about 100 mg ASA without
      particular requirements in patients who need coronary protection.

PMID- 16900308
TI  - Esophageal diverticula: pathogenesis, clinical aspects, and natural history.
AB  - It has been gradually accepted that esophageal diverticula result from esophageal
      motor disorders rather than from primary anatomic abnormalities. Twenty-seven
      patients with these diverticula were evaluated with respect to pathogenesis,
      clinical aspects, diagnostic tests, therapy, and natural history for a mean of 27
      months of followup. Thirteen diverticula were midesophageal, 11 were situated in
      the distal third of the esophagus, and 3 were in both regions. Esophageal
      dysmotility was observed in 85% of patients. Specific esophageal motor disorders
      were more frequent in association with diverticula of the distal third than in
      midesophageal diverticula, suggesting that they result from a pulsion mechanism.
      Traction was the possible mechanism in 27% of midesophageal diverticula.
      Endoscopic esophagitis was seen in one patient and abnormal acid reflux in 25% of
      the cases, mainly in patients with distal diverticula. Distal diverticula
      presented with more severe symptoms than did midesophageal diverticula, and 27%
      of those required surgical treatment. Patients with midesophageal diverticula
      seem to have a better prognosis than those with more distal disease.

PMID- 16900309
TI  - Tufting enteropathy and skeletal dysplasia: is there a link?
AB  - INTRODUCTION: Tufting enteropathy (intestinal epithelial dysplasia), a rare
      congenital enteropathy, presents in the first few months of life with chronic
      watery diarrhoea and impaired growth. The molecular basis for this condition is
      not known. We report our experience with a case of tufting enteropathy that
      developed an unusual skeletal dysplasia with an abnormal blood picture. After
      extensive investigations including repeated gastrointestinal endoscopies and
      biopsies, the diagnosis of tufting enteropathy was made. During the third year of
      her life, the patient's height was static. A full skeletal survey was performed
      and demonstrated features of generalised skeletal dysplasia, some of them
      consistent with those of parastremmatic dwarfism. At the age of five years, she
      developed Coomb's positive haemolytic anaemia and thrombocytopenia with a
      negative auto-antibody screen including anti-enterocyte antibodies. CONCLUSION:
      There might be generalised matrix (including cartilage matrix protein), basement
      membrane abnormalities or both. A secondary protein leak might occur in the
      intestine with autosensitisation and development of autoimmune phenomena. More
      molecular research is needed to identify a possible link.

PMID- 16900310
TI  - Epidemiology and burden of rotavirus diarrhea in day care centers in Lyon,
      France.
AB  - This study gives, for the first time, an estimate of the incidence and the cost
      of rotavirus infection in day care centers in Lyon, France.

PMID- 16900311
TI  - Cardinium symbionts induce haploid thelytoky in most clones of three closely
      related Brevipalpus species.
AB  - Bacterial symbionts that manipulate the reproduction of their host to increase
      their own transmission are widespread. Most of these bacteria are Wolbachia, but
      recently a new bacterium, named Cardinium, was discovered that is capable of the
      same manipulations. In the host species Brevipalpus phoenicis (Acari:
      Tenuipalpidae) this bacterium induces thelytoky by feminizing unfertilized
      haploid eggs. The related species B. obovatus and B. californicus are thelytokous
      too, suggesting that they reproduce in the same remarkable way as B. phoenicis.
      Here we investigated the mode of thelytokous reproduction in these three species.
      Isofemale lines were created of all three species and 19 lines were selected
      based on variation in mitochondrial COI sequences. All B. phoenicis and B.
      californicus lines (10 and 4 lines, respectively) produced males under laboratory
      conditions up to 6.7%. In contrast, males were absent from all B. obovatus lines
      (5 lines). Additional experiments with two B. phoenicis isofemale lines showed
      that males can be produced by very young females only, while older females
      produce daughters exclusively. For most lines it was shown that they are indeed
      feminized by a bacterium as treatment with antibiotics resulted in increased
      numbers of males up to 13.5%. Amplification and identification of specific gyrB
      sequences confirmed that those lines were infected with Cardinium. Three out of
      the five B. obovatus lines did not produce males after treatments with
      antibiotics, nor did they contain Cardinium or any other bacterium that might
      induce thelytoky. In these lines thelytoky is probably a genetic property of the
      mite itself. Despite the different causes of thelytoky, flow cytometry revealed
      that all 19 lines were haploid. Finally, the taxonomic inferences based on the
      mitochondrial COI sequences were incongruent with the classical taxonomy based on
      morphology, suggesting that a taxonomic revision of this group is necessary.

PMID- 16900312
TI  - The ecological distribution of reproductive mode in oribatid mites, as related to
      biological complexity.
AB  - The high incidence of asexuality in oribatid mites presents an unusual
      opportunity for examining hypotheses for the maintenance of sex. There is a
      presumed range in age of asexual species: many oribatid species are
      phylogenetically clustered, occurring in speciose early-derivative families or
      genera without sexual species, while others are phylogenetically isolated from
      other asexual species, occurring in later derivative taxa with sexual congeners.
      We examined the distribution of oribatid mite reproductive mode in soil of corn
      fields, grassy and shrub fields, and forests in central New York State (three
      replicate plots of each type, with 25 samples per plot), to test three ecological
      predictions from current theory. (1) If overall biotic uncertainty, as generated
      by competitors and predators, mediates the ecological distribution of oribatid
      mites, then the proportion of asexual oribatid mites should be negatively
      correlated with biological diversity; we examine this prediction using literature
      data as well. (2) If Muller's Ratchet (the stochastic loss of best genotypes,
      which is independent of environment), mediates the success of asexuality, then no
      ecological pattern should exist. (3) If general purpose genotypes are
      characteristic of asexual oribatid mites, their habitat distribution should be
      broader than that of sexual species. For each plot the level of asexuality was
      compared to indices of overall biotic diversity, as calculated from the pooled
      oribatid mite (competitors) and mesostigmatid mite (predator) communities. We
      found no negative correlation in this relationship in our own data or in the
      literature analysis of 290 faunal surveys from 50 literature sources, so we
      reject biotic uncertainty as an important determinant of reproductive mode
      distribution. When only data on phylogenetically clustered asexuals are
      considered, there is instead a positive correlation between asexuality and
      diversity that is not explained. Because of the latter pattern we tentatively
      reject Muller's Ratchet as the primary factor maintaining reproductive mode in
      these mites, but cannot reject it for isolated asexual species. Niche breadth in
      sexual and asexual oribatid mites provides no support for widespread general
      purpose genotypes but broad patterns in the literature suggest that the idea
      needs further investigation. Possible complicating or unknown factors that are
      discussed include historical disturbance in the study area, the relationship
      between parasitism and general biotic diversity, and the level and source of
      genetic diversity in asexual oribatid mites.

PMID- 16900313
TI  - Ticks (Acari: Ixodidae) parasitizing humans in an Atlantic rainforest reserve of
      Southeastern Brazil with notes on host suitability.
AB  - While conducting projects on ticks from deer and on tick ecology in animal trails
      in an Atlantic rainforest reserve in Southeastern Brazil, researchers of our
      group were bitten by ticks several times. Some of these episodes were recorded.
      Three species of adult ticks attached to humans: Amblyomma brasiliense Aragao,
      Amblyomma incisum Neumann, and Amblyomma ovale Koch. Eight nymphal attachments
      with engorgement on humans were recorded. From these, six molted to adults of A.
      incisum, one to an adult of A. brasiliense, and one had an anomalous molting,
      therefore the adult tick could not be properly identified. Local reactions to
      tick attachment varied among individual hosts from almost imperceptible to
      intense. Especially itching, but hyperemia and swelling as well, were prominent
      features of the reaction. Overall it can be affirmed that human beings can be a
      physiologically suitable host species for ticks in the Atlantic rainforest and
      that itching was an important if not the major component of the resistance to
      tick bite.

PMID- 16900314
TI  - A corrected Haldane's map function to calculate genetic distances from
      recombination data.
AB  - The estimation of genetic distances from recombination data has no direct
      relationship due to the fact that multiple crossovers do not generate recombinant
      gametes that can be recognized in the progeny. The Haldane's map function is the
      most widely used mathematical formulation able to relate the observed
      recombination frequency with the actual number of crossovers. Here I show that
      the model in which the Haldane's correction is based on is not correct, and I
      present a modified map function that takes into consideration the actual number
      of recombinant gametes produced in cells in which different number of crossovers
      have occurred. My correction generates shorter genetic distances than the
      Haldane's one.

PMID- 16900315
TI  - The molecular population genetics of shoot development in Arabidopsis thaliana.
AB  - Studies in Arabidopsis thaliana have provided us with a wealth of information
      about the genetic pathways that regulate plant morphogenesis. This developmental
      genetic treasure trove represents a fantastic resource for researchers interested
      in the microevolution of development. Several laboratories have begun using
      molecular population genetic analyses to investigate the evolutionary forces that
      act upon loci that regulate shoot morphogenesis. Much of this work has focused on
      coding sequence variation in transcription factors; however, recent studies have
      explored sequence variation in other types of proteins and in promoter regions.
      Several genes that regulate shoot development contain signatures of selective
      sweeps associated with positive selection or harbor putative balanced
      polymorphisms in coding and noncoding sequences. Other regulatory genes appear to
      be evolving neutrally, but have accumulated potentially deleterious replacement
      polymorphisms.

PMID- 16900316
TI  - Phenotypic effect of substitution of allelic variants for a histone H1 subtype
      specific for growing tissues in the garden pea (Pisum sativum L.).
AB  - In pea, subtype H1-7 of histone H1 is specific for young actively growing tissues
      and disappears from chromatin of mature tissues. We sequenced the alleles coding
      for three main variants, numbered according to the increase of the
      electrophoretic mobility. Allele 1 differs from the most common allele 2 by eight
      nucleotide substitutions, two of them associated with amino acid replacements,
      His->Tyr in the globular domain and Ala->Val in the C-terminal domain. Allele 3
      differs from alleles 1 and 2 by a 24-bp deletion in the part coding for the C
      terminal domain. In three greenhouse experiments, we compared quantitative traits
      in nearly isogenic lines differing by these H1-7 variants. In experiment 1, three
      lines bearing either of the three allelic variants were compared, the other
      experiments involved pairs of lines bearing variants 1 and 3. In all experiments,
      statistically significant differences between the lines were registered, mostly
      related to the plant size. The most prominent effect was associated with plant
      growth dynamics. Plants of line 3, carrying the 8-amino acid deletion in histone
      H1-7, on average grew slower. In two experiments, the differences of the mean
      stem length persisted throughout plant growth while in experiment 2 differences
      disappeared upon maturity. The H1-7 subtype is supposed to be related to
      maintenance of chromatin state characteristic for cell growth and division.

PMID- 16900317
TI  - Natural selection and divergence in mate preference during speciation.
AB  - Sexual isolation can evolve due to natural selection against hybrids
      (reinforcement). However, many different forms of hybrid dysfunction, and
      selective processes that do not involve hybrids, can contribute to the evolution
      of sexual isolation. Here we review how different selective processes affect the
      evolution of sexual isolation, describe approaches for distinguishing among them,
      and assess how they contribute to variation in sexual isolation among populations
      of Timema cristinae stick-insects. Pairs of allopatric populations of T.
      cristinae living on different host-plant species exhibit greater sexual isolation
      than those on the same host, indicating that some sexual isolation has evolved
      due to host adaptation. Sexual isolation is strongest in regions where
      populations on different hosts are in geographic contact, a pattern of
      reproductive character displacement that is indicative of reinforcement.
      Ecological costs to hybridization do occur but traits under ecological selection
      (predation) do not co-vary strongly with the probability of between-population
      mating such that selection on ecological traits is not predicted to produce a
      strong correlated evolutionary response in mate preference. Moreover, F1 hybrid
      egg inviability is lacking and the factors contributing to reproductive character
      displacement require further study. Finally, we show that sexual isolation
      involves, at least in part, olfactory communication. Our results illustrate how
      understanding of the evolution of sexual isolation can be enhanced by isolating
      the roles of diverse ecological and evolutionary processes.

PMID- 16900318
TI  - Vestibular evoked myogenic potentials: optimal stimulation and clinical
      application.
AB  - By easily stimulating the ear with loud sound and recording on tonically
      contracted neck muscles, vestibular evoked myogenic potential (VEMP) test can
      reflect inner ear function other than the cochlea and semicircular canal. This
      expands the test battery for clinicians to explore saccular disease, adding a
      potential usefulness to the sacculo-collic reflex. The ideal stimulation mode for
      VEMPs is as follows: 95 dB tone bursts, frequency 500 Hz, stimulation repetition
      rate 5 Hz, rise/fall time 1 ms, plateau 2 ms, binaural stimulation with bilateral
      recordings. Animal model using guinea pigs has been established, which sets the
      stage for useful future studies investigating VEMPs in guinea pigs that would
      appear to resemble human VEMP responses. Clinically, VEMP test has been widely
      used in central and peripheral vestibular disorders.

PMID- 16900319
TI  - Identification and functional expression of the pepper pathogen-induced gene,
      CAPIP2, involved in disease resistance and drought and salt stress tolerance.
AB  - A novel pathogen-induced gene, designated CAPIP2, was isolated from pepper leaves
      infected with Xanthomonas campestris pv. vesicatoria. CAPIP2:GFP fusion proteins
      were primarily localized in the cytoplasm. The CAPIP2 transcripts were
      constitutively expressed in the pepper leaves, flowers, and fruits, but were not
      detected in the stems and roots. CAPIP2 gene expression was induced strongly in
      the pepper leaves during pathogen infection, and also after exposure to abiotic
      elicitors and environmental stresses. Ectopic CAPIP2 expression in Arabidopsis
      was accompanied by the expression of Arabidopsis PR-1 and PDF1.2 genes.
      Overexpression of the CAPIP2 gene in Arabidopsis transgenic plants conferred
      enhanced resistance to Pseudomonas syringae pv. tomato DC3000. The CAPIP2
      transgenic Arabidopsis also manifested increased tolerance to high salt, drought
      and oxidative stress during seed germination and seedling state. These results
      suggest that pepper CAPIP2 gene may function as a defense-related gene against
      both biotic and abiotic stresses.

PMID- 16900320
TI  - Degenerated recognition property of a mitochondrial homing enzyme in the
      unicellular green alga Chlamydomonas smithii.
AB  - Target sequence cleavage is the essential step for intron invasion into an
      intronless allele. DNA cleavage at a specific site is performed by an
      endonuclease, termed a homing enzyme, which is encoded by an open reading frame
      within the intron. The recognition properties of them have only been analyzed in
      vitro, using purified, recombinant homing enzyme and various mutated DNA
      substrates, but it is unclear whether the homing enzyme behaves similarly in
      vivo. To answer this question, we determined the recognition properties of I-CsmI
      in vivo. I-CsmI is a homing enzyme encoded by the open reading frame of the alpha
      group I-intron, located in the mitochondrial apocytochrome b gene of the green
      alga Chlamydomonas smithii. The in vivo recognition properties of it were
      determined as the frequency of intron invasion into a mutated target site. For
      this purpose, we utilized hybrid diploid cells developed by crossing alpha-intron
      plus C. smithii to intron-minus C. reinhardtii containing mutated target
      sequences. The intron invasion frequency was much higher than the expected from
      the in vitro cleavage frequency of the respective mutated substrates. Even the
      substrates that had very little cleavage in the in vitro experiment were
      efficiently invaded in vivo, and were accompanied by a large degree of
      coconversion. Considering the ease of the homing enzyme invading into various
      mutated target sequences, we propose that the principle bottleneck for lateral
      intron transmission is not the sequence specificity of the homing enzyme, but
      instead is limited by the rare occurrence of inter-specific cell fusion.

PMID- 16900321
TI  - Tomato defense to the powdery mildew fungus: differences in expression of genes
      in susceptible, monogenic- and polygenic resistance responses are mainly in
      timing.
AB  - Oidium neolycopersici is a causal agent of tomato powdery mildew. In this paper,
      gene expression profiles were investigated of susceptible, monogenic- and
      polygenic resistant tomato genotypes in response to O. neolycopersici infection
      by using cDNA-AFLP. Around 30,000 TDFs (Transcript Derived Fragments),
      representing approximately 22% of the transcriptome based on in silico
      estimation, were identified and 887 TDFs were differentially expressed (DE-TDFs)
      upon inoculation with O. neolycopersici spores. Forty-two percent of the
      identified DE-TDFs were detected in both the compatible and incompatible
      interactions, a subset of these were studied for their temporal patterns. All of
      these common induced DE-TDFs displayed an expression peak at 7 days post
      incoluation in monogenic resistant response but sustained up-regulation in the
      susceptible and the polygenic resistant response. While more than half of these
      common DE-TDFs showed earlier timing in incompatible interactions compared to
      compatible interaction. Only 2% of the identified DE-TDFs were specific to either
      the monogenic or the polygenic resistant response. By annotation of the 230
      sequenced DE-TDFs we found that 34% of the corresponding transcripts were known
      to be involved in plant defense, whereas the other transcripts played general
      roles in signal transduction (11%), regulation (24%), protein synthesis and
      degradation (11%), energy metabolism (12%) including photosynthesis,
      photorespiration and respiration.

PMID- 16900322
TI  - The C-terminal region of alpha' subunit of soybean beta-conglycinin contains two
      types of vacuolar sorting determinants.
AB  - In maturing seed cells, proteins that accumulate in the protein storage vacuoles
      (PSVs) are synthesized on the endoplasmic reticulum (ER) and transported by
      vesicles to the PSVs. Vacuolar sorting determinants (VSDs) which are usually
      amino acid sequences of short or moderate length direct the proteins to this
      pathway. VSDs identified so far are classified into two types: sequence specific
      VSDs (ssVSDs) and C-terminal VSDs (ctVSDs). We previously demonstrated that VSDs
      of alpha' and beta subunits of beta-conglycinin, one of major storage proteins of
      soybean (Glycine max), reside in the C-terminal ten amino acids. Here we show
      that both types of VSDs coexist within this region of the alpha' subunit.
      Although ctVSDs can function only at the very C-termini of proteins, the C
      terminal ten amino acids of alpha' subunit directed green fluorescent protein
      (GFP) to the PSVs even when they were placed at the N-terminus of GFP, indicating
      that an ssVSD resides in the sequence. By mutation analysis, it was found that
      the core sequence of the ssVSD is Ser-Ile-Leu (fifth to seventh residues counted
      from the C-terminus) which is conserved in the alpha and beta subunits and some
      vicilin-like proteins. On the other hand, the sequence composed of the C-terminal
      three amino acids (AFY) directed GFP to the PSVs when it was placed at the C
      terminus of GFP, though the function as a VSD was disrupted at the N-terminus of
      GFP, indicating that the AFY sequence is a ctVSD.

PMID- 16900323
TI  - Identification and expression analysis of cold-regulated genes from the cold
      hardy Citrus relative Poncirus trifoliata (L.) Raf.
AB  - Citrus is a cold-sensitive genus and most commercially important varieties of
      citrus are susceptible to freezes. On the other hand, Poncirus trifoliata (L.)
      Raf. is an interfertile Citrus relative that can tolerate temperatures as low as 
      26 degrees C when fully cold acclimated. Therefore, it has been used for
      improving cold tolerance in cold-sensitive commercial citrus rootstock varieties
      and in attempts to improve scion varieties. In this study, cDNA libraries were
      constructed from both 2-day cold-acclimated and from non-acclimated Poncirus
      seedlings using a subtractive hybridization method with the objective of
      identifying cold-regulated genes. A total of 192 randomly picked clones, 136 from
      the cold-induced library and 56 from the cold-repressed library, were sequenced.
      The majority of these clones showed sequence homology to previously identified
      cold-induced and/or environmental stress-regulated genes in Arabidopsis. In
      addition, some of them shared homology with cold and/or environmental stress
      induced genes previously identified in other herbaceous and woody perennial
      plants and some showed no homology with sequences in GenBank. When these 192
      cDNAs were analyzed by reverse northern blot with cold-acclimated and non
      acclimated probes, 92 of the cDNAs displayed significantly increased expression,
      ranging from 2 to 49-fold, during cold acclimation; all 92 were from the cold
      induced library. Surprisingly no clones displayed significantly repressed
      expression in response to cold. Analysis of a number of selected genes
      individually in northern blots of mRNA from cold-acclimated and non-acclimated
      plants largely confirmed the reverse northern analysis, verifying induction of
      expression of selected cDNAs in response to cold. The results showed that
      subtractive hybridization is an efficient method for identification of cold
      induced genes in plants with limited sequence information available. This study
      also revealed that genes induced during cold acclimation of the cold-hardy citrus
      relative P. trifoliata are similar to those in Arabidopsis, indicating that
      similar pathways may be present and activated during cold acclimation in woody
      perennial plants.

PMID- 16900324
TI  - Ergosterol treatment leads to the expression of a specific set of defence-related
      genes in tobacco.
AB  - Ergosterol is the main sterol of most fungi. Production of reactive oxygen
      species after the treatment of tobacco and tomato cells by nano-molar
      concentrations of ergosterol was previously observed as well as the activation of
      some stress activated mitogen-activated protein kinases on alfalfa cells. In this
      paper, the expression of some defence-related genes after the ergosterol
      treatment of tobacco Nicotiana tabacum plants is reported. The gene expression of
      pathogenesis related proteins of families PR1, PR3, PR5 and proteinase inhibitors
      of class I and II together with enzymes participating in the defence response,
      such as phenylalanine-ammonia lyase and sesquiterpene cyclase, were monitored by
      RT-qPCR. In addition, the concentrations of salicylic acid, an important
      signalling molecule, increased in time due to the enzyme activation. On the other
      hand, ergosterol did not provoke tissue necrosis and the possible cross-talk
      between the signalling pathways of salicylate and jasmonate was observed.
      Collected data shows that ergosterol is able to activate the expression of a
      number of defence genes and could increase resistance against pathogens.

PMID- 16900325
TI  - Loss of Necrotic Spotted Lesions 1 associates with cell death and defense
      responses in Arabidopsis thaliana.
AB  - We isolated a lesion mimic mutant, necrotic spotted lesions 1 (nsl1), from Ds
      tagged Arabidopsis thaliana accession No-0. The nsl1 mutant exhibits a growth
      retardation phenotype and develops spotted necrotic lesions on its rosette and
      cauline leaves. These phenotypes occur in the absence of pathogens indicating
      that nsl1 mutants may constitutively express defense responses. Consistent with
      this idea, nsl1 accumulates high levels of callose and autofluorescent phenolic
      compounds localized to the necrotic lesions. Furthermore RNA gel blot analysis
      revealed that genes associated with disease resistance activation are upregulated
      in the nsl1 mutants and these plants contain elevated levels of salicylic acid
      (SA). Crossing nsl1 with an SA deficient mutant, eds16-1, revealed that the nsl1
      lesions and growth retardation are dependent upon SA. The nsl1 phenotypes are not
      suppressed under either the rar1-10 or sgt1b-1 genetic background. NSL1 encodes a
      novel 612aa protein which contains a membrane-attack complex/perforin (MACPF)
      domain, which is conserved in bacteria, fungi, mammals and plants. The possible
      modes of action of NSL1 protein in negative regulation of cell death programs and
      defense responses are discussed.

PMID- 16900327
TI  - Simultaneous saccharification and L-(+)-lactic acid fermentation of protease
      treated wheat bran using mixed culture of lactobacilli.
AB  - Protease-treated wheat bran (20% w/v) of particle size less than 300 microm
      containing 65% (w/w) starch was used for the simultaneous saccharification and L
      (+)-lactic acid fermentation by the mixed cultures of Lactobacillus casei and
      Lactobacillus delbrueckii. Maximum lactate yield after various process
      optimizations was 123 g l(-1) with a productivity of 2.3 g l(-1) h(-1)
      corresponding to a conversion of 0.95 g lactic acid per gram starch after 54 h at
      37 degrees C. By using protease-treated wheat bran around tenfold decrease in
      supplementation of the costly medium component, like yeast extract, was achieved
      together with a considerable increase in the production level.

PMID- 16900326
TI  - Nature of stress and transgene locus influences transgene expression stability in
      barley.
AB  - Stress and the nature of the transgene locus can affect transgene expression
      stability. These effects were studied in two, stably expressing, T6 populations
      of barley (Hordeum vulgare): bombardment-mediated, multi-copy lines with
      ubiquitin-driven bar and uidA or single-copy lines from Ds-mediated gene delivery
      with ubiquitin-driven bar alone. Imposing the environmental stresses, water and
      nutrient deprivation and heat shock, did not reproducibly affect transgene
      expression stability; however, high frequencies of heritable transcriptional gene
      silencing (TGS) occurred following in vitro culture after six generations of
      stable expression in the multi-copy subline, T3#30, but not in the other lines
      studied. T3#30 plants with complete TGS had epigenetic modification patterns
      exactly like those in an identical sibling subline, T3#31, which had significant
      reduction in transgene expression in the T3 generation and was completely
      transcriptionally silenced in the absence of imposed stresses in the T6
      generation. Complete TGS in T3#30 plants correlated with methylation in the 5'UTR
      and intron of the ubi1 promoter complex and condensation of chromatin around the
      transgenes; DNA methylation likely occurred prior to chromatin condensation.
      Partial TGS in T3#30 also correlated with methylation of the ubi1 promoter
      complex, as occurred with complete TGS. T3#30 has a complex transgene structure
      with inverted repeat transgene fragments and a 3'-LTR from a barley
      retrotransposon, and therefore the transgene locus itself may affect its tendency
      to silence after in vitro culture and transgene silencing might result from host
      defense mechanisms activated by changes in plant developmental programming and/or
      stresses imposed during in vitro growth.

PMID- 16900328
TI  - Microbial production of 1,3-propanediol by Klebsiella pneumoniae using crude
      glycerol from biodiesel preparations.
AB  - 1,3-Propanediol (1,3-PD) was produced by Klebsiella pneumoniae using crude
      glycerol obtained from biodiesel production. The 1,3-PD concentration of 51.3
      g/l(-1) on crude glycerol from alkali-catalyzed methanolysis of soybean oil was
      comparable to that of 53 g/l(-1) on crude glycerol derived from a lipase
      catalyzed process. The productivities of 1.7 g l(-1) h(-1) on crude glycerol were
      comparable to that of 2 g l(-1) h(-1) on pure glycerol. It could be concluded
      that the crude glycerol could be directly converted to 1,3-PD without any prior
      purification.

PMID- 16900329
TI  - Purification and characterization of a family 5 endoglucanase from a moderately
      thermophilic strain of Bacillus licheniformis.
AB  - Strains of thermophilic bacilli were screened for cellulolytic activity by gel
      diffusion assay on selective medium at 55 degrees C. Strain B-41361, identified
      as a strain of Bacillus licheniformis, displayed activity against
      carboxymethylcellulose. Zymogram analysis demonstrated several catalytically
      active polypeptides with the most prominent species having a mass of 37 kDa. The
      enzyme was purified 60-fold with a 17% yield and specific activity of 183 U/mg.
      The amino terminal sequence was homologous to members of glycoside hydrolase
      family 5. Optimal temperature was 65 degrees C (measured over 30 min), but the
      enzyme was most stable at 60 degrees C, retaining greater than 90% activity after
      one hour. The enzyme had a broad pH range, with maximal activity at pH 6.0, 75%
      maximal activity at pH 4.5, and 40% at pH 10. The enzyme hydrolyzed p
      nitrophenylcellobioside, barley beta-glucan, and lichenan, but no activity was
      detected against avicel or acid-swollen cellulose.

PMID- 16900330
TI  - Transport kinetics of ectoine, an osmolyte produced by Brevibacterium epidermis.
AB  - Brevibacterium epidermis DSM 20659 is a halotolerant Gram-positive bacterium
      which can synthesize the osmolyte, ectoine, but prefers to take it up from its
      environment. The present study revealed that B. epidermis is equipped with at
      least one transport system for ectoine, with a maximal transport velocity of 15.7
      +/- 4.3 nmol/g CDW.min. The transport requires energy (ATP) and is completely
      inhibited by the proton uncoupler, CCCP. The ectoine uptake system is
      constitutively expressed at a basal level of activity and its activity is
      immediately 10-fold increased by hyper-osmotic stress. Initial uptake rates are
      not influenced by the intensity of the hyper-osmotic shock but the duration of
      the increased activity of the uptake system could be directly related to the
      osmotic strength of the assay solution. Competition assays indicate that betaine,
      but not proline, is also transported by the ectoine uptake system.

PMID- 16900331
TI  - A retrovirus-based system to stably silence hepatitis B virus genes by RNA
      interference.
AB  - RNA interference (RNAi) might be an efficient antiviral therapy for some
      obstinate illness. Herein, a retrovirus-based RNAi system was developed to drive
      expression and delivery of Hepatitis B virus (HBV)-specific short hairpin RNA
      (shRNA) in HepG2 cells. The levels of HBsAg and HBeAg and that of HBV mRNA were
      dramatically decreased by this RNAi system in HepG2 cells transfected with Topo
      HBV plasmid. Retrovirus-based RNAi thus may be useful for therapy in HBV and
      other viral infections and provide new clues for prophylactic vaccine
      development.

PMID- 16900332
TI  - Sclerotiorin, from Penicillium frequentans, a potent inhibitor of aldose
      reductase.
AB  - Aldose reductase, the first key enzyme in the polyol pathway, is involved in
      complications of diabetes. Sclerotiorin, isolated and purified from the fermented
      broth of Penicillium frequentans, inhibited aldose reductase with an IC(50 )0.4
      microM. The inhibitor also showed antibacterial activity against Bacillus spp.

PMID- 16900333
TI  - Permeabilization and lysis induced by bacteriocins and its effect on aldehyde
      formation by Lactococcus lactis.
AB  - Permeabilization induced by lacticin 3147, lactococcins A, B and M, enterocin AS
      48 and nisin, bacteriocins described as cell membrane-pore forming and lytic
      agents, enhanced in all cases aldehyde formation by Lactococcus lactis IFPL730.
      Nevertheless, the conversion of isoleucine into 2-methylbutyraldehyde depended
      not only on the degree of permeabilization but also on the bacteriocin that
      caused the cell membrane damage. The highest values of 2-methylbutyraldehyde
      corresponded to cell suspensions containing lacticin 3147 and lactococcins,
      treatments that provoked further lysis in addition to induced permeabilization.

PMID- 16900334
TI  - Chemoenzymatic dynamic kinetic resolution of rac-1-phenylethanol in ionic liquids
      and ionic liquids/supercritical carbon dioxide systems.
AB  - Continuous dynamic kinetic resolution processes in different ionic
      liquid/supercritical carbon dioxide biphasic systems were carried out by
      simultaneously using both immobilized Candida antarctica lipase B (Novozym 435)
      and silica modified with benzenosulfonic acid (SCX) catalysts at 40 degrees C and
      10 MPa. SCX was seen to act as an efficient heterogeneous chemical catalyst for
      the racemization of (S)-1-phenylethanol in different ionic liquid media
      ([emim][NTf(2)], [btma][NTf(2)] and [bmim][PF(6)]). Coating both chemical and
      enzymatic catalysts with ILs greatly improved the efficiency of the process,
      providing a good yield (76%) of (R)-1-phenylethyl propionate product with
      excellent enantioselectivity (ee = 91-98%) in continuous operation.

PMID- 16900335
TI  - Comparison of relative mRNA quantification models and the impact of RNA integrity
      in quantitative real-time RT-PCR.
AB  - Relative quantification in quantitative real-time RT-PCR is increasingly used to
      quantify gene expression changes. In general, two different relative mRNA
      quantification models exist: the delta-delta Ct and the efficiency-corrected Ct
      model. Both models have their advantages and disadvantages in terms of
      simplification on the one hand and efficiency correction on the other. The
      particular problem of RNA integrity and its effect on relative quantification in
      qRT-PCR performance was tested in different bovine tissues and cell lines (n =
      11). Therefore different artificial and standardized RNA degradation levels were
      used. Currently fully automated capillary electrophoresis systems have become the
      new standard in RNA quality assessment. RNA quality was rated according the RNA
      integrity number (RIN). Furthermore, the effect of different length of amplified
      products and RNA integrity on expression analyses was investigated. We found
      significant impact of RNA integrity on relative expression results, mainly on
      cycle threshold (Ct) values and a minor effect on PCR efficiency. To minimize the
      interference of RNA integrity on relative quantification models, we can recommend
      to normalize gene expression by an internal reference gene and to perform an
      efficiency correction. Results demonstrate that innovative new quantification
      methods and normalization models can improve future mRNA quantification.

PMID- 16900336
TI  - Elevated expression of human alpha-1 antitrypsin mediated by yeast intron in
      Pichia pastoris.
AB  - Intron-mediated enhancement has been documented in many cases to involve large
      positive effect on gene expression. To address this, human Alpha-1 antitrypsin
      (hAAT) gene was integrated into Pichia pastoris with and without a yeast intron
      generated from the final plasmid pBlu-exII-int-exIII and ligated into the
      EcoRI/BamHI multiple cloning site of the yeast shuttle vector pHIL-S1. The
      chimeric exon-intron complex in the middle of the naturally occurring hAAT exons
      II and III caused a 23-fold enhancement of hAAT expression in P. pastoris,
      measured through SDS-PAGE and immunoblot analyses.

PMID- 16900337
TI  - [Surgery continuing education in Austria, Switzerland and in Germany: 3 country
      discussion of concepts and comparison of curriculum structure].

PMID- 16900340
TI  - Announcing the winner of the 2006 Kurt Jellinger Prize.

PMID- 16900339
TI  - Comparison of short-term outcomes of laparoscopic vs open approaches to ileal
      pouch surgery.
AB  - AIMS: The present meta-analysis compared short-term outcomes between patients
      undergoing laparoscopic and open restorative proctocolectomy. METHODS: A
      literature search of Medical Literature Analysis and Retrieval System Online,
      Ovid, Excerpta Medica and Cochrane databases was performed to identify studies
      published between 1990 and 2006 comparing laparoscopic and open restorative
      proctocolectomy. A random-effect meta-analytical technique was used, and
      sensitivity analysis was performed on studies published since 2001, higher
      quality papers, those reporting on more than 30 patients and those with matching
      of patient characteristics. RESULTS: Ten studies satisfied the selection
      criteria, including outcomes on 329 patients, 168 (51.1%) of whom underwent
      laparoscopic resection. Operative time was significantly longer in the
      laparoscopic group by 86 min (p<0.001) and throughout the subgroup analysis, but
      this finding was associated with significant heterogeneity. Operative blood loss
      was less in the laparoscopic group by 84 ml. There was no significant difference
      in post-operative adverse events between the groups. A statistically significant
      reduction in length of post-operative stay was observed for laparoscopic patients
      in high-quality studies and those reporting on more than 30 patients by 1.1 days
      (p=0.02 in both subgroups) and studies published in or since 2001 by 3.0 days
      (p=0.004) but not overall. CONCLUSION: Laparoscopic ileal pouch surgery was
      associated with longer operative time, lower blood loss, shorter length of
      hospital stay and similar short-term adverse events compared with open surgery.
      Comparative data on quality of life and long-term outcomes are currently
      unavailable. The potential advantage of laparoscopic ileal pouch surgery remains
      to be established.

PMID- 16900341
TI  - Dementia lacking distinctive histology (DLDH) revisited.
AB  - Although immunohistochemistry has helped to classify the histology of
      frontotemporal lobar degeneration (FTLD), there have been many cases, described
      in the literature as showing "dementia lacking distinctive histology" (DLDH), in
      which this technique has failed to disclose signature pathological changes. Using
      an automated procedure we have repeated immunostaining for ubiquitin protein
      (UBQ) in 41 patients with FTLD, 25 of whom were previously considered, on the
      basis of UBQ immunostaining performed in Manchester, UK, to show FTLD-ubiquitin
      (FTLD-U) histology and 16 described as DLDH. Both the quality and amount of UBQ
      immunoreactive (UBQ-ir) pathology (neurites and intraneuronal cytoplasmic
      inclusions) was significantly increased using the newer staining method. Although
      the original histological diagnosis was confirmed in the 25 cases previously
      classified as FTLD-U, the median UBQ score for slides stained in Vancouver
      increased significantly compared to those stained in Manchester. More
      importantly, however, some degree of UBQ-ir changes was now disclosed in 13 of
      the 16 cases previously classified as DLDH and these were now classed as definite
      or probable FTLD-U. Of the remaining three DLDH cases, clinical diagnostic
      uncertainties could have explained the lack of specific pathology in two
      instances. Hence, we conclude that DLDH is a very rare disorder, and that lack of
      sensitivity for UBQ immunostaining is likely responsible for the failure to
      disclose this pathology and to provide a diagnosis of FTLD-U.

PMID- 16900342
TI  - Expression of cell kinetics and death during monocyte-macrophage differentiation:
      effects of Actinomycin D and Vinblastine treatments.
AB  - The different effects of two cytostatic drugs, Actinomycin D and Vinblastine,
      during macrophage-like differentiation induced in THP-1 monocytic cell line by
      phorbol ester phorbol 12-myristate 13-acetate (PMA) (6, 30, and 60 nM), were
      studied by morpho-cytochemical approaches. In PMA-unstimulated monocytic cells,
      the cytostatic effects of Actinomycin D (an antimetabolic drug) were
      characterized by a drastic reduction of the G2/M cells accompanied by dramatic
      death of the G1 cells; on the contrary, Vinblastine (a microtubule
      depolymerizating drug) induced an accumulation of the G2/M cells with the
      appearance of aneugenic micronuclei and scarce cell death mainly from the G1
      cells. After 60 nM PMA stimulation, the culture was mostly composed by
      macrophagic cells characterized by low proliferation and the appearance of mono
      /binucleated polyploid cells; in this condition, the cytotoxicity of the two
      drugs, more effective for Vinblastine, induced cell death in the different ploidy
      classes (2c, 4c, 8c). Cell death appeared to be of apoptotic nature, but with
      some morpho-phenotypic differences due to the action mechanism of the drugs and
      dependent on cell culture growth and differentiation. As a consequence of the
      different block-action of the two drugs on the cell cycle phases and in relation
      to the different subcellular targets, the effects changed during the transition
      from not-adhering/proliferating monocytes to adhering/low-proliferating
      differentiated macrophages.

PMID- 16900343
TI  - Pregnancy, thrombophlebitis and thromboembolism: what every obstetrician should
      know.
AB  - Thrombophlebitis is caused by superficial venous thrombosis and vascular
      inflammatory changes affecting the lower limbs. The condition is often
      encountered in pregnancy and symptomatic treatment including compression and
      analgesia are commonly employed. The obstetrician may become involved in the
      management of thrombophlebitis; however the potential for embolic complications,
      and need for adequate assessment remain widely unrecognised. This case report
      highlights pitfalls in the management of thrombophlebitis, in particular the
      dangers of clinical assessment without the use of Doppler ultrasound and the
      potential for deep venous extension and embolic complications. The case also
      documents the use of low molecular-weight heparin in pregnancy to prevent such
      complications and promote thrombus resolution; a review of the available
      treatment options, including surgery, is included. Whilst thromboembolism remains
      a leading cause of maternal death, the potential dangers of symptomatic
      thrombophlebitis should not be overlooked.

PMID- 16900344
TI  - Rh alloimmunization: Doppler or amniotic fluid analysis in the prediction of
      fetal anemia?
AB  - OBJECTIVE: Compare the results of amniocentesis and those of middle cerebral
      artery peak systolic velocity to detect anemic fetuses in Rh alloimmunized
      pregnancies. METHOD: Descriptive observational study involving 99 consecutive Rh
      negative pregnancies: 74 alloimmunized patients submitted to amniotic fluid
      spectrophotometry (group 1) and 25 alloimmunized cases managed with Doppler
      ultrasonography (group 2). Variables analyzed were the following: need for
      neonatal transfusion and neonatal hematocrit. RESULT: Neonatal hematocrit was
      significantly lower and the need for neonatal transfusion was significantly
      higher in cases managed with spectrophotometry compared to those managed with
      Doppler. CONCLUSION: Infants managed with Doppler velocimetry had higher
      hematocrit and less need for neonatal transfusion, suggesting that this non
      invasive method of monitoring fetal anemia may best preserve the neonate.

PMID- 16900345
TI  - Intrauterine hemorrhage from an umbilical cord ulcer associated with fetal
      duodenal atresia: a case report.
AB  - In the recent years, the association between congenital intestinal atresia and
      umbilical cord ulceration has been demonstrated; however, this complication is
      rarely encountered. To the best of our knowledge, only 14 cases on this
      association have been published previously. We encountered a case of acute
      intrauterine hemorrhage from an umbilical cord ulcer in a fetus with duodenal
      atresia that resulted in early neonatal death. There is little information
      available on the association between congenital intestinal atresia and umbilical
      cord ulceration. Greater understanding may alter the obstetric management.
      Although the prevention of sudden perinatal death is considered to be difficult,
      frequent fetal monitoring and detailed ultrasonographic examinations may
      facilitate the early detection of this condition, thereby enabling the rescue of
      the affected fetuses. Further investigation is required to establish the
      management protocol.

PMID- 16900346
TI  - [Transesophageal echocardiography for non-cardiac surgery patients: superfluous
      luxury or essential diagnostic tool?].
AB  - BACKGROUND: The value of transesophageal echocardiography (TEE) in non-cardiac
      critically ill patients has barely been studied. MATERIALS AND METHODS: Over a
      period of 4 years TEE was used prospectively to evaluate patients with acute
      hemodynamic instability in non-cardiac critically ill patients in addition to
      standard care. RESULTS: A total of 363 TEE studies were performed in 339 selected
      patients. Volume depletion (169/47%) and regional wall motion abnormalities
      (97/27%) were the most frequent findings followed by global left ventricular
      dysfunction (79/22%). Of the TEE studies, 203 (56%) provided additional
      information with therapeutic relevance in 164 (45%) cases. CONCLUSIONS:
      Transesophageal echocardiography provides additional information in critically
      ill non-cardiac patients with unexplained hemodynamic instability. In the
      majority of cases a clinical diagnosis is confirmed or improvement of volume
      resuscitation and catecholamine therapy can be achieved. In the minority of
      patients the results of TEE lead to distinct changes in medical management.
      Whether this improved diagnostic accuracy favours outcome, still needs to be
      evaluated.

PMID- 16900348
TI  - Regulation of galectin-1 expression by transforming growth factor beta1 in
      metastatic mammary adenocarcinoma cells: implications for tumor-immune escape.
AB  - Tumors escape from immune surveillance by producing immunosuppressive cytokines
      and proapototic factors, including TGF-beta and galectin-1 (Gal-1). Since
      immunosuppressive mechanisms might act in concert to confer tumor-immune
      privilege, we investigated the potential cross talk between TGF-beta and Gal-1 in
      highly metastatic mammary adenocarcinoma (LM3) cells. While Gal-1 treatment was
      not capable of regulating TGF-beta synthesis, a pronounced and dose-dependent
      increase in Gal-1 expression was observed when tumor cells were treated with TGF
      beta(1. )This effect was also observed in the murine lung adenocarcinoma LP07 and
      in the human breast adenocarcinoma MCF-7 cell lines. TGF-beta1-mediated
      upregulation of Gal-1 expression was specifically mediated by TbetaRI and
      TbetaRII, since it was abrogated when LM3 cells were infected with retroviral
      vectors expressing the dominant negative forms of these receptors. In addition,
      gal-1 gene sequence analysis revealed the presence of three putative binding
      sites for Smad4 and Smad3 transcription factors, consistent with the ability of
      TGF-beta(1) to trigger a Smad-dependent signaling pathway in these cells. Thus,
      TGF-beta(1) may trigger a Smad-dependent pathway to control Gal-1 expression,
      suggesting that distinct mechanisms might cooperate in tilting the balance toward
      an immunosuppressive environment at the tumor site.

PMID- 16900349
TI  - A genetic linkage map for tef [Eragrostis tef (Zucc.) Trotter].
AB  - Tef [Eragrostis tef (Zucc.) Trotter] is the major cereal crop in Ethiopia. Tef is
      an allotetraploid with a base chromosome number of 10 (2n = 4x = 40) and a genome
      size of 730 Mbp. Ninety-four F(9) recombinant inbred lines (RIL) derived from the
      interspecific cross, Eragrostis tef cv. Kaye Murri x Eragrostis pilosa (accession
      30-5), were mapped using restriction fragment length polymorphisms (RFLP), simple
      sequence repeats derived from expressed sequence tags (EST-SSR), single
      nucleotide polymorphism/insertion and deletion (SNP/INDEL), intron fragment
      length polymorphism (IFLP) and inter-simple sequence repeat amplification (ISSR).
      A total of 156 loci from 121 markers was grouped into 21 linkage groups at LOD 4,
      and the map covered 2,081.5 cM with a mean density of 12.3 cM per locus. Three
      putative homoeologous groups were identified based on multi-locus markers.
      Sixteen percent of the loci deviated from normal segregation with a predominance
      of E. tef alleles, and a majority of the distorted loci were clustered on three
      linkage groups. This map will be useful for further genetic studies in tef
      including mapping of loci controlling quantitative traits (QTL), and comparative
      analysis with other cereal crops.

PMID- 16900350
TI  - Indicators to assess temporal genetic diversity in the French Catalogue: no
      losses for maize and peas.
AB  - The aim of this study, led by the GEVES (Research and Control Group for Varieties
      and Seeds), was to suggest indicators to assess the diversity available to
      farmers since the French Official Catalogue for Plant Varieties and Species was
      initiated. The largest datasets of 1990 inbred maize lines and 578 pea lines from
      the last 50 years were analysed using morphological and enzymatic parameters.
      Lines were grouped into three to five periods. Genetic diversity was estimated in
      each period from morphological and enzymatic markers by computing numerous
      indices, such as the number of classes of scores for each characteristic, allelic
      richness or genetic diversity index (H ( e )). Population differentiation
      parameters (G(ST), G(ST)', F(ST), Q(ST)) were also estimated between periods.
      While genetic diversity computed from distinction, uniformity, stability traits
      was more marked for maize (0.66) than for garden peas (0.35) or feed peas (0.29),
      the opposite trend was observed with enzymes, resulting in a genetic diversity of
      0.43, 0.35 and 0.22 for garden peas, feed peas and maize, respectively. However,
      no significant changes in genetic diversity were observed over time, and genetic
      differentiation was slight between periods. All our results demonstrated that no
      significant reduction in the diversity available to farmers had been observed
      since initiation of the French Catalogue. The H ( e ) was a good indicator
      providing a quantitative estimate of genetic diversity, but it should be
      interpreted alongside a more precise indicator such as allelic richness or the
      number of classes for morphological characteristics.

PMID- 16900351
TI  - Calibration of a 220Rn flow-through source.
AB  - Two reference methods have been established to calibrate the yield of a self-made
      220Rn flow-through source. These reference methods include (a) a small
      scintillation cell flow-through method and (b) a gamma spectrometry method that
      takes advantage of an activated charcoal. The methods were validated
      theoretically and experimentally including intercomparison measurements. It is
      shown that the source is stable with a relative deviation less than 2.5% over 5
      years, when the relative humidity ranged from 50 to 90%, and the temperature from
      5 to 38 degrees C. The 220Rn monitor used in these reference methods is
      calibrated without a 220Rn gas source with determinate yield. On the basis of the
      calibration of the 220Rn source by the methods mentioned above, the accurate
      calibration of any 220Rn monitor by the self-made 220Rn source with stable yield
      is feasible.

PMID- 16900352
TI  - Increasing utilization of computed tomography in the adult emergency department,
      2000-2005.
AB  - This study aims to characterize changes in computed tomography (CT) utilization
      in the adult emergency department (ED) over a 5-year period. CT scans ordered on
      adult ED patients from July 2000 to July 2005 were analyzed in five groups: head,
      cervical spine, chest, abdomen, and miscellaneous. ED patient volume and triage
      acuity scores were determined. Triage acuity scores are used to determine the
      severity of a patient's illness or injury and the need for immediate evaluation
      and treatment. There were 46,553 CT scans performed on 27,625 adult patients in
      the ED during the study period. During this same period, 194,622 adult patients
      were evaluated in the ED. From 2000 to 2005, the adult emergency department
      patient volume increased by 13% while triage acuity remained stable. During this
      same period, head CT increased by 51%, cervical spine CT by 463%, chest CT by
      226%, abdominal CT by 72%, and miscellaneous CT by 132%. Although increases were
      generally greater for patients over age 40, the increase in those less than 40
      years was also substantial. Of the 4,320 individual patients who underwent chest
      CT, 83 (2%) had chest CT on three or more separate ED visits. Of 10,960 patients
      undergoing abdominal CT, 406 (4%) had abdominal CT on three or more separate ED
      visits. ED CT utilization has increased at a rate far exceeding the growth in ED
      patient volume. This presumably reflects the improved utility of CT in diagnosing
      serious pathology, its increased availability, and a desire on the part of
      physicians for diagnostic certainty. Whether this increase in utilization results
      in improved patient outcomes is at present unclear and deserves additional study.

PMID- 16900353
TI  - Microsatellite instability analysis of bilateral breast tumors suggests treatment
      related origin of some contralateral malignancies.
AB  - PURPOSE: High-frequency microsatellite instability (MSI-H) occurs frequently in
      colorectal cancers and some other tumor types, but is very uncommon in breast
      cancer. In the earlier study devoted to microsatellite analysis of allelic
      imbalances, the authors accidentally detected several MSI-H tumors in patients
      with the bilateral form of breast cancer (biBC). The present study was designed
      to examine this unexpected phenomenon in more detail. METHODS: All DNA samples
      were tested by the standard panel of MSI-specific markers BAT25, BAT26, BAT40,
      D5S346, and D17S250. If the tumor was unstable for at least one marker, or PCR
      amplification was not successful for any of the listed above loci, the analysis
      of additional five dinucleotide markers (D1S225, D11S4167, D22S272, D22S1166, and
      D3S3527) was performed. Tumors showing instability in > or = 30% loci were
      classified as MSI-H. RESULTS: In biBC group, MSI-H status was detected in 6/60
      (10%) contralateral tumors, but in 0/50 (0%) first malignancies (P = 0.021) and
      only in 1/22 (5%) synchronous biBC (P = 0.434). None of 52 unilateral breast
      cancers showed MSI-H status. Shifts of mononucleotide markers were revealed in
      four second carcinomas from biBC patients but in none of the breast tumors from
      other categories. CONCLUSIONS: MSI-H is detected with a noticeable frequency in
      bilateral but not in unilateral breast cancers. Preferable occurrence of MSI-H in
      second metachronous tumors from biBC patients allows to hypothesize that the
      development of some contralateral breast neoplasms is casually related to the
      adjuvant treatment of the initial malignancy.

PMID- 16900354
TI  - Comparison of the use of the humerus intramedullary nail and dynamic compression
      plate for the management of diaphyseal fractures of the humerus. A randomised
      controlled study.
AB  - The aim of this study was to compare the results of the humerus intramedullary
      nail (IMN) and dynamic compression plate (DCP) for the management of diaphyseal
      fractures of the humerus. Forty-seven patients with diaphyseal fracture of the
      shaft of the humerus were randomised prospectively and treated by open reduction
      and internal fixation with IMN or DCP. The criteria for inclusion were grade 1 or
      2a compound fractures, polytrauma, early failure of conservative treatment and
      unstable fractures. The patients with pathological fractures, grade 3 open
      fractures, refractures and old neglected fractures of the humerus were excluded
      from the study. Twenty-three patients underwent internal fixation by IMN and 24
      by DCP. Reamed antegrade nailing was done in all cases. DCP was done through an
      anterolateral or posterior approach. The outcome was assessed in terms of the
      union time, union rate, functional outcome and the incidence of complications.
      Functional outcome was assessed using the American Shoulder and Elbow Surgeons'
      Score (ASES). On comparing the results by independent samples t test, there was
      no significant difference in ASES scores between the two groups (P>0.05). The
      average union time was found to be significantly lower for IMN as compared to DCP
      (P<0.05). The union rate was found to be similar in both groups. Complications
      such as infection were found to be higher with DCP as compared to IMN, while
      shortening of the arm (1.5-4 cm) and restriction of shoulder movements due to
      impingement by the nail were found to be higher with IMN as compared to DCP.
      However, this improved in all patients following the removal of the nail once the
      fracture had healed. This study proves that IMN can be considered a better
      surgical option for the management of diaphyseal fractures of the humerus as it
      offers a short union time and lower incidence of serious complications like
      infection. However, there appears to be no difference between the two groups in
      terms of the rate of union and functional outcome.

PMID- 16900355
TI  - HO prevention and the combined therapeutic protocol--do we really need it?

PMID- 16900356
TI  - Impact of new lamellar techniques of keratoplasty on eye bank activity.
AB  - BACKGROUND: Deep anterior lamellar keratoplasty (DALK) has become an increasingly
      popular alternative to penetrating keratoplasty in patients with stromal corneal
      pathologies. The main advantages of DALK are: prevention of long-term endothelial
      loss, elimination of allograft reaction and short topical steroid treatment with
      lower risks of glaucoma, cataract and infection. Because this technique enables
      surgeons to use corneal grafts with low endothelial density, the aim of this
      paper was to determine whether this type of innovation has had a significant
      impact on eye bank activity. METHODS: We reviewed our corneal graft activity over
      a 40-month period and assessed the proportion of deep lamellar and penetrating
      keratoplasties. During the same period, we also evaluated our eye bank activity
      and recorded the utilisation of grafts with endothelium abnormalities, which were
      only suitable for lamellar techniques. RESULTS: Deep lamellar keratoplasty
      represented 29.8% (85 out of 285) of corneal transplantations. Forty-eight
      percent of all corneas stored at the local eye bank were unsuitable for
      penetrating keratoplasty; 36.6% of those were not suitable for endothelial
      deficiencies. Among these, 72.7% were used for DALK and 27.3% were rejected. This
      permitted a 24.5% increase in corneal grafting activity. In contrast, Descemet's
      membrane was removed at the time of surgery in 12% of corneas with healthy
      endothelium, which was used for deep lamellar keratoplasty. CONCLUSIONS: Deep
      anterior lamellar keratoplasty development and close collaboration between eye
      banks and surgeons can induce a significant increase in corneal grafting. This
      could be a partial solution in countries confronted with corneal graft shortages.

PMID- 16900357
TI  - Efficacy of plasmin enzymes and chondroitinase ABC in creating posterior vitreous
      separation in the pig: a masked, placebo-controlled in vivo study.
AB  - BACKGROUND: Induction of posterior vitreous detachment (PVD) during vitrectomy
      helps to prevent proliferative complications, but can be traumatic to the retina,
      particularly in young patients. Adjunct enzymes have been proposed to facilitate
      PVD. We investigated the efficacy of enzymes in creating PVD as an adjunct to
      vitrectomy in the pig. METHODS: Five groups of 8 pigs received a masked
      intravitreal injection of chondroitinase (1 IU), human (0.4 or 1.3 activity units
      [AU]) or porcine plasmin (0.18 AU or 0.47 AU) into one eye, and osmolarity
      adjusted control into the other. After incubation, a core vitrectomy was
      performed on each eye at low suction, without vitreous peeling. The occurrence of
      spontaneous PVD and its extent were graded. Eyes were investigated using scanning
      electron microscopy (SEM) and transmission electron microscopy (TEM). Vitreous
      remnants on the retina were quantified in SEM. Data were analyzed using McNemar's
      test for paired observations and Wilcoxon paired signed rank test. RESULTS:
      Spontaneous PVD occurred more frequently in human plasmin-treated eyes (p<0.025)
      and all plasmin eyes (p<0.025) than in placebo controls. The extent of PVD
      appeared larger in human plasmin (p<0.025) and all plasmin-treated eyes
      (p<0.025). In plasmin-treated eyes, SEM morphometry showed a significant
      reduction in the vitreous-covered retina areas. Chondroitinase failed to produce
      an effect. CONCLUSIONS: Plasmin may prove a useful adjunct to conventional
      vitrectomy.

PMID- 16900359
TI  - Computed tomography dose and variability of airway dimension measurements: how
      low can we go?
AB  - BACKGROUND: Quantitative CT shows promise as an outcome measure for cystic
      fibrosis (CF) lung disease in infancy, but must be accomplished at a dose as low
      as reasonably achievable. OBJECTIVE: To determine the feasibility of ultra-low
      dose CT for quantitative measurements of airway dimensions. MATERIALS AND
      METHODS: Two juvenile pigs were anesthetized and their lungs scanned at 25 cm
      H(2)O face-mask pressure in apnoea using beam currents of 5, 10, 20, 40 and 100
      mAs. The lumen diameters and wall thicknesses of matched airways (n=22) at each
      dose were measured by two observers using validated software. Measurement
      variability at each dose was compared to that at 100 mAs (reference dose) for
      large and small airways (lumen diameter <2.5 mm). RESULTS: Lowering CT dose (mAs)
      affected measurement variability for lumen diameter of small and large airways
      (P<0.001) and for wall thickness of small (P<0.001), but not large (P=0.63),
      airways. To obtain the same measurement variability at 5 mAs as at 100 mAs, four
      to six small airways or one to three large airways have to be measured and
      averaged. CONCLUSION: Quantitative airway measurements are feasible on images
      obtained at as low as 5 mAs, but more airways need to be measured to compensate
      for greater measurement variability.

PMID- 16900358
TI  - Comparative study of topical anti-allergic eye drops on human conjunctiva-derived
      cells: responses to histamine and IFN gamma and toxicological profiles.
AB  - BACKGROUND: The purpose of the study was to compare toxic effects and responses
      to histamine and IFN gamma associated with the use of some widely used anti
      allergic eye drops commercially available today. METHODS: For dynamic studies,
      the Wong-Kilbourne cell line was stimulated for 24 h with histamine or IFN gamma
      in the presence or absence of anti-allergic eye drops. Supernatants of histamine
      stimulated cells were evaluated for the production of IL-6 and IL-8 by ELISA,
      while the expression of ICAM-1 was evaluated by flow cytometry on IFN gamma
      stimulated cells. Toxicological assays were performed using cold light
      cytofluorometry: viability and apoptosis as well as reactive oxygen species (ROS)
      and O2(.)- production were assessed using neutral red, Hoechst/propidium iodide,
      H(2)-DCFDA and hydroethidine tests, respectively. RESULTS: Antihistamines reduced
      IL-6 release and presented dose-dependent inhibitory effects on IL-8 production.
      None of the eye drops decreased the basal or IFN gamma-stimulated expression of
      ICAM-1. Conversely, eye drops preserved with benzalkonium chloride (BAC) induced
      even higher ICAM-1 expression levels on IFN gamma-stimulated cells than did IFN
      gamma alone, whereas unpreserved drugs had no effect. Toxicological assays
      confirmed the pivotal role of BAC in proportionally reducing cell viability while
      increasing apoptosis and oxidative stress. CONCLUSIONS: The ability of topical
      ocular anti-H(1) drugs to significantly reduce the production of IL-6 and IL-8
      argues that they may help treat the inflammatory processes occurring in allergic
      ocular surface disorders. Nevertheless, preserved ophthalmic formulations may
      enhance epithelial conjunctival expression of ICAM-1 in the presence of a low
      inflammatory stimulus, such as IFN gamma, and displayed toxic as well as pro
      oxidative effects on these cells. Therefore, BAC used as preservative might in
      part interfere with the potential anti-inflammatory properties of the active
      compound by modulating the immuno-inflammatory response of epithelial
      conjunctival cells.

PMID- 16900360
TI  - Excitatory and inhibitory after-effects after repetitive magnetic transcranial
      stimulation (rTMS) in normal subjects.
AB  - We investigated the post-train effects of repetitive transcranial magnetic
      stimulation (rTMS) on motor evoked potential (MEP) size and cortical silent
      period (SP) duration. rTMS was delivered over the primary motor cortex in trains
      of 5, 10, 20, 40 and 60 stimuli in normal subjects at rest and in trains of 5, 10
      and 20 stimuli during voluntary muscle contraction. The intensity of stimulation
      was 120% of resting motor threshold. Test MEPs were delivered at different
      interstimulus intervals after rTMS ended. At rest, 5 Hz trains produced an
      increase in the MEP size that persisted after the end of the trains. Trains of 5
      stimuli produced after-effects that persisted for 0.5 s, whereas trains of 40 and
      60 stimuli produced a facilitation that lasted for several seconds. 5 Hz-rTMS
      delivered during muscle contraction increased the SP duration during stimulation
      but the increase persisted for only 1 s after the train ended. The present
      experiments show that the after-effects of rTMS on MEP amplitude and SP duration
      have different time-courses. rTMS probably elicits its after-effects on
      excitatory and inhibitory cortical elements through different physiological
      mechanisms.

PMID- 16900362
TI  - Spatial coding for the Simon effect in visual search.
AB  - Two experiments were conducted to examine the Simon effect (i.e., faster
      responding when irrelevant stimulus location corresponds with response location
      than when it does not) in visual search tasks. The search items were arranged in
      a 4 x 4 grid, and grid locations were coded into sets of four, two involving
      inner columns and two involving outer columns. In experiment 1, three different
      types of inefficient search tasks were used. The Simon effects were shown to be
      larger when the target appeared in one of the outer columns than in one of the
      inner columns ("laterality effect"). This pattern of results was not observed
      when distractors were absent, suggesting that the laterality effect depends on
      the operation of selective attention. In experiment 2, a pop-out search task was
      used, and no significant effect of target location on the Simon effect was found.
      Interpretations of the results based on the attention-shift account and
      referential-coding account were discussed.

PMID- 16900361
TI  - Effect of unilateral vestibular deafferentation on the initial human vestibulo
      ocular reflex to surge translation.
AB  - Transient whole-body surge (fore-aft) translation at 0.5 G peak acceleration was
      administered to six subjects with unilateral vestibular deafferentation (UVD),
      and eight age-matched controls. Subjects viewed eccentric targets to determine if
      linear vestibulo-ocular reflex (LVOR) asymmetry might lateralize otolith
      deficits. Eye rotation was measured using magnetic search coils. Immediately
      before surge, subjects viewed a luminous target 50 cm away, centered or displaced
      10 degrees horizontally or vertically. The target was extinguished during
      randomly directed surges. LVOR gain relative to ideal velocity in subjects with
      UVD for the contralesional horizontally eccentric target (0.59 +/- 0.08, mean +/-
      SEM) did not differ significantly from normal (0.50 +/- 0.04), but gain for the
      ipsilesional eccentric target (0.35 +/- 0.02) was significantly less than normal
      (0.48 +/- 0.03, P < 0.05). Normal subjects had mean gain asymmetry for
      horizontally eccentric targets of 0.17 +/- 0.03, but asymmetry in UVD was
      significantly increased to 0.35 +/- 0.05 (P < 0.05). Four of six subjects with
      UVD had maximum gain asymmetry outside normal 95% confidence limits. Asymmetry
      did not correlate with UVD duration. Gain for 10 degrees vertically eccentric
      targets averaged 0.38 +/- 0.14 for subjects with UVD, insignificantly lower than
      the normal value of 0.75 +/- 0.15 (P > 0.05). Surge LVOR latency was symmetrical
      in UVD, and did not differ significantly from normal. There was no significant
      difference in response between dark and visible target conditions until 200 ms
      after surge onset. Chronic human UVD, on average, significantly impairs the surge
      LVOR for horizontally eccentric targets placed ipsilesionally, but this asymmetry
      is small relative to interindividual variation.

PMID- 16900363
TI  - Multisensory integration of speech signals: the relationship between space and
      time.
AB  - Integrating audiovisual cues for simple events is affected when sources are
      separated in space and time. By contrast, audiovisual perception of speech
      appears resilient when either spatial or temporal disparities exist. We
      investigated whether speech perception is sensitive to the combination of spatial
      and temporal inconsistencies. Participants heard the bisyllable /aba/ while
      seeing a face produce the incongruent bisyllable /ava/. We tested the level of
      visual influence over auditory perception when the sound was asynchronous with
      respect to facial motion (from -360 to +360 ms) and emanated from five locations
      equidistant to the participant. Although an interaction was observed, it was not
      related to participants' perception of synchrony, nor did it indicate a linear
      relationship between the effect of spatial and temporal discrepancies. We
      conclude that either the complexity of the signal or the nature of the task
      reduces reliance on spatial and temporal contiguity for audiovisual speech
      perception.

PMID- 16900364
TI  - [Stage appropriate therapy for COPD].
AB  - The treatment of chronic obstructive pulmonary disease (COPD) has improved
      substantially over recent years, and is increasingly based on evidence from
      prospective studies. Cessation of smoking is the most important and effective
      single measure which can be taken. In the early stages, intensive measures for
      nicotine withdrawal should be taken to prevent the catastrophic effects of
      disease progression. Pharmacological treatment of COPD in the earlier stages (0
      II) should be symptom oriented. Asymptomatic patients at these stages do not
      require permanent pharmacotherapy. From Stage II, COPD patients benefit from
      pulmonary rehabilitation programs. Patients with stages III and IV should usually
      be put on long-term corticosteroid inhalation, preferably in combination with
      long-acting bronchodilators. Systemic corticosteroids, even at low doses, are not
      indicated. They are useful only for the short-term treatment of acute
      exacerbations. These treatment modalities improve the quality of life and
      morbidity of COPD patients. They also decrease exacerbations and hospitalization
      rates, which should help to reduce mortality due to this important disease.

PMID- 16900365
TI  - [The Berlin Urological Society from 1912 to 2006].
AB  - The influence of the "Berlin Urologists' School" led to the founding of the
      Berlin Urological Society (BUS) in 1912. In his foundation speech, C. Posner
      spoke of the no longer appropriate division between internal medicine and
      surgery, and hoped for the rapid recognition of urology as an independent
      specialist discipline in Germany. Thus, BUS was initially a purely scientific
      body which did not consider the political position or economic interests of the
      Berlin urologists. In 1955, urology became independent after its complete
      separation from surgery. Today, the main aim of the society is again the
      dissemination of specialist scientific knowledge.

PMID- 16900366
TI  - [Retroperitoneal bronchogenic cyst].
AB  - We describe a 35-year-old female patient who underwent surgery because of a
      coincidentally occurring cryptic tumour near the left adrenal gland and a right
      renal carcinoma (pT1, N0, G2, R0). The left-sided tumour was intraoperatively
      identified as a cystic structure filled with secretion. Histopathological
      analysis provided the diagnosis of a bronchogenic cyst.

PMID- 16900367
TI  - [Villous adenoma of the renal pelvis and ureter].
AB  - Villous adenomas of the urinary tract are extremely rare tumours belonging to the
      adenoepithelial metaplasias. They can be associated with other neoplasias,
      especially with carcinomas. We describe the case of an 85-year-old female patient
      suffering from a villous adenoma of the renal pelvis and ureter.

PMID- 16900368
TI  - [Laparoscopic pelvic surgery: Where do we stand in the year 2006?].
AB  - Laparoscopic radical prostatectomy has become an equivalent alternative to the
      open retropubic approach, offering the advantages of minimally invasive surgery.
      It is being applied increasingly in Germany and the rest of Europe. Whether the
      surgical robot da Vinci will be used for this procedure to the same extent as in
      the United States is unpredictable because of high investment and maintenance
      costs. Similarly, laparoscopic sacrocolpopexy has proven to be a viable option
      compared to open transabdominal or transvaginal surgery, showing a significant
      reduction in postoperative morbidity. The value of radical cystectomy is
      controversial despite proven feasability. On one hand, the technical difficulties
      of purely laparoscopic urinary diversion result in very long operating times, and
      in the case of the laparoscopically assisted creation of a neobladder, the
      advantage of this approach has to be questioned. On the other hand, a maximum
      rate of 30% of local recurrences and distant metastases indicates at least poor
      patient selection. In conclusion, this procedure should be limited to a few
      experienced centers.

PMID- 16900369
TI  - [The position of laparoscopic surgery in pediatric urology].
AB  - With growing experience in laparoscopic techniques there is a switch in
      pediatrics from ablative surgery to reconstructive procedures. Besides the
      established procedures such as laparoscopic nephrectomy and orchidopexy,
      procedures like heminephrectomy and pyeloplasty have proven practicable and
      become standard therapies in children and infants. Due to technical advances, as
      shown for our own patients, the number of treated infants is still increasing.
      However, laparoscopic reconstructive procedures presuppose a good deal of
      experience in preparation and suture techniques, and remain reserved for centers
      with daily experience in laparoscopy. Daily experience with difficult urological
      laparoscopic procedures in adults will remain more common than in pediatric
      centres.

PMID- 16900371
TI  - MZ3 induces apoptosis in human leukemia cells.
AB  - PURPOSE: 4-(4-Bromophenyl)-2,3-dihydro-N,3-bis(3,4,5-trimethoxyphenyl)-2-oxoidmi
      dazole-1-carboxamide (MZ3) is one of the synthesized combretastatin-A-4 analogues
      and has been reported that it displayed a promising specific activity against
      leukemia cell lines. Our purpose was to investigate the mechanism of MZ3's
      cytotoxicity. METHODS: Cytotoxicity was measured by MTT method, apoptosis was
      measured by flow cytometry. DNA fragmentation was tested by agarose gel
      electrophoresis. Mitochondrial membrane potential (DeltaPsim) was detected by JC1
      staining and flow cytometry, while intracellular reactive oxygen species (ROS)
      was detected by 5-(and-6)-carboxy-2'-7'-dichlorofluorescin diacetate staining and
      flow cytometry. Protein expression was analyzed by western blotting. In vivo
      activity of MZ3 was assayed through severe combined immunodeficiency (SCID) mice
      model of human leukemia engrafts. RESULTS: MZ3 exhibited high anti-cancer
      activity in six leukemia cell lines, including two drug-resistant cell lines. MZ3
      induced DNA fragmentation, and caused an elevation of ROS and a loss of DeltaPsim
      in HL60 cells. MZ3 also induced the activation of caspase-3, influenced the
      expression of Bcl-2 family members, MAPKs and other proteins relative to
      mitochondria-induced apoptosis. In addition, N-acetylcysteine cannot inhibit HL60
      cell apoptosis caused by MZ3. Furthermore, a prolonged survival time was observed
      after treatment with MZ3 in SCID mice model of human leukemia engrafts.
      CONCLUSIONS: MZ3 is a potent compound against leukemia cell lines both in vitro
      and in vivo, and the mitochondrial pathway mediated by Bcl-2 protein family and
      MAPKs might be involved in signaling MZ3-induced apoptosis.

PMID- 16900370
TI  - [Renal cell carcinoma].

PMID- 16900372
TI  - Additive antitumor effect of concurrent treatment of 4-hydroxy tamoxifen with 5
      fluorouracil but not with doxorubicin in estrogen receptor-positive breast cancer
      cells.
AB  - PURPOSE: The sequential addition of tamoxifen (TAM) to chemotherapy seems
      superior to its concurrent addition in patients with breast cancer. This study
      was conducted to clarify the hypothesis that there are differential interactions
      among TAM and chemotherapeutic agents. METHODS: Estrogen receptor (ER)-alpha
      positive or -negative breast cancer cells were treated with 4-hydroxy TAM (4OHT),
      5-fluorouracil (FU) and/or doxorubicin (Dox). Changes in the expression levels of
      genes related to sensitivity and resistance to TAM, 5-FU or Dox were tested.
      RESULTS: Concurrent treatment of 4OHT with 5-FU but not with Dox additively
      inhibited the growth of ER-alpha-positive cells. 5-FU did not change the
      expression levels of any tested genes related to either sensitivity or resistance
      to TAM. Although Dox did not change the expression levels of any genes related to
      the sensitivity to TAM, Dox significantly increased the expression levels of some
      genes related to TAM resistance, Eph A-2, ER-beta, Fos and vascular endothelial
      growth factor. 4OHT significantly decreased thymidilate synthase (TS) activity.
      CONCLUSIONS: Although the antitumor effect of concurrent 4OHT and 5-FU was
      additive, that of concurrent 4OHT and Dox was less than additive in ER-alpha
      positive cells. The increased expression of genes related to TAM resistance by
      Dox might be responsible for the interaction. Decreased TS activity by 4OHT might
      increase the antitumor activity of 5-FU. These findings may provide a preclinical
      rationale for concurrent use with 5-FU and TAM.

PMID- 16900373
TI  - Defensins- and cathepsin G-ANCA in systemic lupus erythematosus.
AB  - In this study, we examined the content of antineutrophil cytoplasmic antibodies
      (ANCA) against defensins and cathepsin G in sera from systemic lupus
      erythematosus (SLE) patients and their significance in estimating the activity of
      SLE. Defensins- and cathepsin G-ANCA in sera from 28 patients with SLE, eight
      patients with rheumatoid arthritis (RA) and eight patients with microscopic
      polyangitis (mPA) were measured by ELISA. Significantly increased defensins- and
      cathepsin G-ANCA were found in sera of patients with SLE and mPA when compared
      with the value of normal controls. Though significantly higher defensins- and
      cathepsin G-ANCA were detected in both active and inactive SLE patients, the
      value in active SLE patients was significantly higher than inactive SLE patients.
      After the therapy with high dose of prednisolone, the serum level of defensins-
      and cathepsin G-ANCA was decreased, and this decrease was sustained for at least
      16 weeks. This study suggests that defensins- and cathepsin G-ANCA may serve as
      useful markers of the disease activity of SLE.

PMID- 16900374
TI  - Purpura and serum mixed cryoglobulinemia in psoriatic arthritis.
AB  - We here firstly describe the case of a psoriatic arthritis associated with
      cutaneous purpura and lower limbs weakness. The presence of type III mixed
      cryoglobulinemia in serum was the only possible detected cause. Discrepancies
      with the hepatitis C virus-related mixed cryoglobulinemia picture are discussed.

PMID- 16900375
TI  - HLA-DR alleles in patients with post-streptococcal reactive arthritis.

PMID- 16900376
TI  - Cyclosporine A as treatment of esophageal involvement in dermatomyositis.
AB  - We report a case of a 70-year-old man with dermatomyositis complicated by
      esophageal involvement resistant to corticosteroid therapy. It had serious and
      potentially life-threatening implications, resulting in impossible oral feeding.
      This condition was successfully resolved by administration of cyclosporine A.

PMID- 16900377
TI  - Molecular cloning and early expression of chick embryo SCO-spondin.
AB  - SCO-spondin is a multidomain glycoprotein secreted by the subcommissural organ
      (SCO). It belongs to the thrombospondin type 1 repeat superfamily and has been
      identified in several vertebrate species. We report the cloning of the chick SCO
      spondin ortholog and examine its temporal and spatial expression during early
      embryogenesis from Hamburger and Hamilton (HH) stage 12 to HH stage 21. Chick SCO
      spondin cDNA contains a long open reading frame encoding a predicted protein of
      5255 amino acids. Northern blot analysis has revealed SCO-spondin mRNA as a band
      of about 15 kb. Many conserved domains have been identified, including 27
      thrombospondin type 1 repeats, 13 low-density lipoprotein receptor type A
      domains, one EMI domain (a cysteine-rich domain of extracellular proteins), three
      von Willebrand factor type D domains, and one cystine knot C-terminal domain.
      Whole-mount in situ hybridization enabled the first signal of mRNA expression to
      be detected at HH stage 17, exclusively in a thin area of the prosencephalon roof
      plate. During the following stages of development, SCO-spondin expression
      remained restricted to this region. The multidomain structure of SCO-spondin and
      its early expression suggest that it plays a role in developmental processes in
      the central nervous system.

PMID- 16900378
TI  - Carotid angioplasty with stenting for chronic internal carotid artery occlusion:
      technical note.
AB  - INTRODUCTION: Carotid angioplasty with stenting (CAS) is becoming accepted as an
      effective and reliable treatment option for severe carotid artery stenosis.
      However, it is rarely applied for carotid occlusion, especially in its chronic
      stage. We report our experience of CAS for chronic internal carotid artery
      occlusion representing compromised cerebral blood flow using various protection
      methods. METHODS: A 77-year-old woman, who was already diagnosed with severe left
      internal carotid artery stenosis, suddenly had right hemiparesis and aphasia. At
      that time, she was treated conservatively because her neurological status was
      quite good, in spite of left carotid artery occlusion. Her symptoms improved in
      the short term, except slight aphasia, but deteriorated again 18 days from the
      onset, and magnetic resonance imaging (MRI) showed new ischemic lesions. CAS was
      then performed for the occluded carotid artery on the 23rd day from the first
      onset. RESULTS: Using the proximal protection technique, the occluded lesion was
      crossed carefully with a microguidewire. Stents were also placed successfully
      with the distal protection technique. The occluded carotid artery was completely
      recanalized without any unfavorable events or neurological deterioration.
      CONCLUSION: In this patient, CAS was successfully to treat chronic carotid artery
      occlusion. These procedures and techniques are reviewed and discussed.

PMID- 16900379
TI  - Characterization of the Mn2+-stimulated (di)adenosine polyphosphate hydrolase
      encoded by the Deinococcus radiodurans DR2356 nudix gene.
AB  - The DR2356 nudix hydrolase gene from Deinococcus radiodurans has been cloned and
      the product expressed as an 18 kDa histidine-tagged protein. The enzyme
      hydrolysed adenosine and diadenosine polyphosphates, always generating ATP as one
      of the initial products. ATP and other (deoxy)nucleoside triphosphates were also
      substrates, yielding (d)NDP and Pi as products. The DR2356 protein was most
      active at pH 8.6-9.0 and showed a strong preference for Mn(2+) as activating
      cation. Mg(2+) ions at 15 mM supported only 5% of the activity achieved with 2 mM
      Mn(2+). K (m) and k (cat) values for diadenosine tetra-, penta- and
      hexaphosphates were 2.0, 2.4 and 1.1 microM and 11.4, 28.6 and 12.0 s(-1),
      respectively, while for GTP they were 20.3 microM and 1.8 s(-1), respectively.
      The K (m )for adenosine 5'-pentaphosphate was <1 microM. Expression analysis
      showed the DR2356 gene to be induced eight- to ninefold in stationary phase and
      in cells subjected to slow dehydration plus rehydration. Superoxide (but not
      peroxide) treatment and rapid dehydration caused a two-to threefold induction.
      The Mn-requirement and induction in stationary phase suggest that DR2356 may have
      a specific role in maintenance mode metabolism in stationary phase as Mn(2+)
      accumulates.

PMID- 16900380
TI  - Evaluation of the molecular recognition of monoclonal and polyclonal antibodies
      for sensitive detection of 2,4,6-trinitrotoluene (TNT) by indirect competitive
      surface plasmon resonance immunoassay.
AB  - Detection of TNT is an important environmental and security concern all over the
      world. We herein report the performance and comparison of four immunoassays for
      rapid and label-free detection of 2,4,6-trinitrotoluene (TNT) based on surface
      plasmon resonance (SPR). The immunosensor surface was constructed by
      immobilization of a home-made 2,4,6-trinitrophenyl-keyhole limpet hemocyanin
      (TNPh-KLH) conjugate onto an SPR gold surface by simple physical adsorption
      within 10 min. The immunoreaction of the TNPh-KLH conjugate with four different
      antibodies, namely, monoclonal anti-TNT antibody (M-TNT Ab), monoclonal anti
      trinitrophenol antibody (M-TNP Ab), polyclonal anti-trinitrophenyl antibody (P
      TNPh Ab), and polyclonal anti-TNP antibody (P-TNP Ab), was studied by SPR. The
      principle of indirect competitive immunoreaction was employed for quantification
      of TNT. Among the four antibodies, the P-TNPh Ab prepared by our group showed
      highest sensitivity with a detection limit of 0.002 ng/mL (2 ppt) TNT. The lowest
      detection limits observed with other commercial antibodies were 0.008 ng/mL (8
      ppt), 0.25 ng/mL (250 ppt), and 40 ng/mL (ppb) for M-TNT Ab, P-TNP Ab, and M-TNP
      Ab, respectively, in the similar assay format. The concentration of the conjugate
      and the antibodies were optimized for use in the immunoassay. The response time
      for an immunoreaction was 36 s and a single immunocycle could be done within 2
      min, including the sensor surface regeneration using pepsin solution. In addition
      to the quantification of TNT, all immunoassays were evaluated for robustness and
      cross-reactivity towards several TNT analogs.

PMID- 16900381
TI  - Development of a bienzyme system for the electrochemical determination of nitrate
      in ambient air.
AB  - This work reports the development of a bienzyme system consisting of salicylate
      hydroxylase (SHL) and nitrate reductase (NaR) for the electrochemical
      determination of nitrate. This method measures the concentration of nitrate
      directly under ambient air without suffering from oxygen interferences. The
      determination is based on the detection of NADH consumption, and the principle is
      as follows: NADH initiates the irreversible decarboxylation and hydroxylation of
      salicylate by SHL in the presence of oxygen to produce catechol, which results in
      a detectable signal due to its oxidation at the working electrode; the second
      enzyme, NaR, in the presence of nitrate, reduced the availability of NADH, and
      consequently, the current difference after the injection of nitrate is
      proportional to its concentration. This method shows high performance
      characteristics for nitrate determination with a broad detection range between 10
      microM and 1,000 microM, a short measuring time of around 5 min, and a simple
      operation without sample pretreatment by inert gas purge or oxygen scavenger.

PMID- 16900382
TI  - In situ characterisation of a microorganism surface by Raman microspectroscopy:
      the shell of Ascaris eggs.
AB  - Intestinal nematodes are very common human parasites and a single species,
      Ascaris lumbricoides, is estimated to infect a quarter of the world's population.
      A sticky external layer covers their eggs. This work shows that Raman vibrational
      confocal spectroscopy is able to give information on the biochemical composition
      of the shell of Ascaris eggs. The biochemical localised characterisation of
      Ascaris eggs was performed directly on the eggs in their aqueous environment. The
      studied parasites came from two origins: dissections of adult females and
      extractions from biosolid sludges. The presence of mucopolysaccharides, proteins
      and chitin in the shell was demonstrated. The presence of ascaroside compounds
      was shown particularly via the narrow and intense bands from the organised long
      CH2 chains. To the best of our knowledge, this is the first time that the latter
      have been observed in Raman vibrational spectra of microorganisms. Hydration of
      the shell was different depending on the intensity of the colour of the sludge
      eggs. Knowledge of the biochemical structural properties of egg surfaces would be
      useful to understand the egg adhesion phenomena on vegetables contaminated by
      reused wastewater.

PMID- 16900383
TI  - Paricalcitol versus calcitriol treatment for hyperparathyroidism in pediatric
      hemodialysis patients.
AB  - Secondary hyperparathyroidism (SHPT) remains a treatment dilemma in pediatric
      dialysis patients. Recent experience with paricalcitol (P), a vitamin D analogue,
      in adults with SHPT has shown equal efficacy and improved survival compared to
      traditional treatment with calcitriol (C). We present our experience with (C)
      compared to (P) treatment in our pediatric dialysis patients with SHPT. Twenty
      one patients (mean age 11.5+/-5 years) with SHPT (intact parathyroid hormone
      (iPTH) averaging 1,228+/-496 pg/ml) were studied. Seventeen received (C) followed
      by (P); while an additional four were treated with either (C=1) or (P=3) alone.
      After 26+/-8 weeks, average percent (%) decrease in iPTH was similar with (C) and
      (P) (-60.4+/-34% versus -65.4+/-28%, respectively; p=0.6). In the (P) group, the
      effective dose in children was greater than in adult trials based on kilogram
      weight. Episodes of hypercalcemia between the treatment groups were not
      different. However, episodes of elevated calcium x phosphorus product (CaxP)> or
      =70 mg(2)/dl(2) occurred more frequently in the (C) group (odds ratio=1.5;
      p=0.01). Paricalcitol appears to be safe and effective in pediatric patients.
      Data suggest that dosing should be gauged according to degree of SHPT. This
      should serve as impetus for future pharmacokinetic studies in pediatric dialysis
      patients.

PMID- 16900384
TI  - Neonatal disease in neutral endopeptidase alloimmunization: lessons for
      immunological monitoring.
AB  - Neutral endopeptidase (NEP) alloimmunization has recently been determined to
      cause severe forms of neonatal disease as a result of the transplacental passage
      of anti-NEP antibodies. However there is a wide spectrum of neonatal disease
      variability. We present the medical histories of a large family, specifically of
      two alloimmunized sisters in their second pregnancy in whom we established the
      basis of immunological surveillance and therapeutic intervention during pregnancy
      and after delivery. One mother developed dramatically high titers of IgG1 and
      IgG4, and was treated with IvIg and one plasma exchange, both of which
      substantially reduced the anti-NEP Ab titer. However, the neonatal syndrome
      observed in her infant was severe, partly due to treatment delay. Anti-NEP Ab
      were also found in the mother's milk and the infant's urine. In contrast, the
      other mother had a normal second pregnancy and delivered a healthy neonate, which
      was related to the fact that she only produced the non-complement activating IgG4
      subclass of anti-NEP antibodies. Thus, anti-NEP Ab (titer and subclass) seem to
      be highly sensitive biomarkers of neonatal risk. Interventional strategy aimed at
      reducing anti-NEP titer, should be started early during pregnancy and, possibly,
      even before pregnancy in those mothers producing anti-NEP IgG1. Careful
      monitoring of anti-NEP Ab titer and subclass is mandatory in NEP-deficient
      mothers during their pregnancies.

PMID- 16900385
TI  - [Inpatient infusion treatment for acute tinnitus with and without adjuvant
      psychotherapeutic intervention. A comparison of psychological effectiveness].
AB  - Two groups of tinnitus patients (n=93) were recruited, one of which was treated
      with standard infusion therapy and further acute medical intervention, while the
      other obtained an additional psychotherapeutic intervention. Questionnaires and
      interviews were taken at beginning of the treatment, and 9 days and 3 years after
      treatment. The accompanying psychotherapeutic intervention consisted primarily of
      client-centered counseling, guided relaxation techniques from clinical hypnosis,
      and some standard and tinnitus-related methods for a better coping with stress.
      After 9 days, both treatment groups showed significant improvement in several
      psychological characteristics. However, there was no evidence for the superiority
      of the combined treatment with psychological intervention. Psychotherapeutic
      treatment accompanying the acute medical treatment probably shows better
      effectiveness in an ambulant setting with both patients and medical healthcare
      professionals rating it as 'very helpful'. This pilot study has contributed
      initial results for the integrated treatment of the acute tinnitus and has helped
      in the development of further therapeutic strategies as well as an evidence based
      concept for further evaluation. This study received one of the two scientific
      first prizes of the "German Tinnitus League".

PMID- 16900386
TI  - [ASA and the inner ear. An old acquaintance in a new light].

PMID- 16900387
TI  - Reg (regenerating) gene overexpression in islets from non-obese diabetic mice
      with accelerated diabetes: role of IFNbeta.
AB  - AIMS/HYPOTHESIS: The expression of IFNbeta in beta cells results in accelerated
      type 1 diabetes. The REG family of beta cell proliferation factors have been
      described as autoantigens in autoimmune diabetes. The aim of this study was to
      determine the effect of IFNbeta on Reg expression, and the implications of this
      in terms of autoimmunity. METHODS: Reg gene expression was determined in islets
      from non-obese diabetic (NOD) RIP-HuIFNbeta mice by cDNA microarray, quantitative
      real-time PCR and immunohistochemistry. The effect of IFNbeta on Reg1 and Reg2
      expression was assessed in the NOD insulinoma cell line NIT-1. IL-6, known to
      induce Reg expression, was measured in the insulitis microenvironment.
      Morphological studies were carried out to determine islet enlargement in this
      model. RESULTS: Reg2 was upregulated in islets from the NOD RIP-HuIFNbeta mice at
      the onset of the autoimmune attack. IFNbeta upregulates Reg1 and Reg2 genes in
      NIT-1 cells. The expression of Il6 was increased in islets from transgenic mice
      and in NIT-1 cells exposed to HuIFNbeta. Moreover, islets from transgenic mice
      were enlarged compared with those from wild-type mice.
      CONCLUSIONS/INTERPRETATION: Reg overexpression correlates well with the
      acceleration of diabetes in this model. The upregulation of Reg suggests that
      islets try to improve hyperglycaemia by regenerating the cells lost in the
      autoimmune attack. Reg expression is regulated by several factors such as
      inflammation. Therefore, the overexpression of an IFNbeta-induced autoantigen
      (REG) in the islets during inflammation might contribute to the premature onset
      of diabetes.

PMID- 16900388
TI  - Behavior of mice with mutations in the conserved region deleted in
      velocardiofacial/DiGeorge syndrome.
AB  - Velocardiofacial/DiGeorge syndrome (VCFS/DGS) is a developmental disorder caused
      by a 1.5 to 3-Mb hemizygous 22q11.2 deletion. VCFS/DGS patients display
      malformations in multiple systems, as well as an increased frequency of
      neuropsychiatric defects including schizophrenia. Haploinsufficiency of TBX1
      appears to be responsible for these physical malformations in humans and mice,
      but the genes responsible for the neuropsychiatric defects are unknown. In this
      study, two mouse models of VCFS/DGS, a deletion mouse model (Lgdel/+) and a
      single gene model (Tbx1 +/-), as well as a third mouse mutant (Gscl -/-) for a
      gene within the Lgdel deletion, were tested in a large behavioral battery
      designed to assess gross physical features, sensorimotor reflexes, motor activity
      nociception, acoustic startle, sensorimotor gating, and learning and memory.
      Lgdel/+ mice contain a 1.5-Mb hemizygous deletion of 27 genes in the orthologous
      region on MMU 16 and present with impairment in sensorimotor gating, grip
      strength, and nociception. Tbx1 +/- mice were impaired in grip strength similar
      to Lgdel/+ mice and movement initiation. Gscl -/- mice were not impaired in any
      of the administered tests, suggesting that redundant function of other Gsc family
      members may compensate for the loss of Gscl. Thus, although deletion of the genes
      in the Lgdel region in mice may recapitulate some of the behavioral phenotypes
      seen in humans with VCFS/DGS, these phenotypes are not found in mice with
      complete loss of Gscl or in mice with heterozygous loss of Tbx1, suggesting that
      the neuropsychiatric and physical malformations of VCFS/DGS may act by different
      genetic mechanisms.

PMID- 16900389
TI  - Efficacy of neem seed extract shampoo on head lice of naturally infected humans
      in Egypt.
AB  - Sixty heavily lice-infested male and female children (4-15 years) were selected
      and subjected to the treatment with a neem seed extract shampoo. Twenty to thirty
      milliliter of the shampoo were thoroughly mixed with completely wet hair and
      rubbed in to reach the skin of the scalp. After 5, 10, 15 and 30 min, the shampoo
      was washed out and the hair basically combed. Head lice were collected and
      examined. The neem seed extract shampoo proved to be highly effective against all
      stages of head lice. No obvious differences regarding the efficacy of the shampoo
      were observed between an exposure time of 10, 15 or 30 min. No side effects, such
      as skin irritation, burning sensations, or red spots on the scalp, forehead or
      neck, respectively, were observed.

PMID- 16900390
TI  - Exploiting our knowledge of NF-kappaB signaling for the treatment of mammary
      cancer.
AB  - Nuclear Factor-kappaB (NF-kappaB) has been implicated in the lobuloalveolar
      development of the mammary gland. In breast cancer its activation has been linked
      to tumor progression via stimulation of cell proliferation, pro-survival, and
      angiogenesis pathways and metastasis. Whether NF-kappaB activation in the immune
      system influences mammary cancer remains unclear. In addition to the constitutive
      activation frequently found in mammary carcinoma tissue, radio- and
      chemotherapeutic agents used in the treatment of mammary cancer can lead to
      activation of NF-kappaB. This effect has been postulated to contribute to the
      development of resistance to these agents and suggests the use of NF-kappaB
      inhibitors as sensitizers for therapy. The review describes principle targets and
      drugs used to inhibit NF-kappaB function and discusses future perspectives in the
      use of these inhibitors for the treatment of mammary cancer.

PMID- 16900391
TI  - The mTOR pathway in breast cancer.
AB  - There is currently a wealth of information regarding the mutations that
      contribute to cancer development. Most of these mutations alter the expression
      and activity of signal transduction proteins. The current goal in cancer therapy
      is to use our knowledge of the molecular alterations in a cancer cell to choose
      the most appropriate signal transduction inhibitor for an individual patient. The
      topic of this review is the mammalian target of rapamycin (mTOR) kinase signaling
      pathway, which is aberrantly activated in many types of human cancer. We will
      discuss the mTOR pathway and the potential mechanisms that contribute to its
      activation in cancer, together with data relating to the potential for inhibitors
      targeting the mTOR-signaling pathway to impact on breast cancer therapy.

PMID- 16900394
TI  - Development of a mathematical model of the human circulatory system.
AB  - A mathematical lumped parameter model of the human circulatory system (HCS) has
      been developed to complement in vitro testing of ventricular assist devices.
      Components included in this model represent the major parts of the systemic HCS
      loop, with all component parameters based on physiological data available in the
      literature. Two model configurations are presented in this paper, the first
      featuring elements with purely linear constitutive relations, and the second
      featuring nonlinear constitutive relations for the larger vessels. Three
      different aortic compliance functions are presented, and a pressure-dependent
      venous flow resistance is used to simulate venous collapse. The mathematical
      model produces reasonable systemic pressure and flow behaviour, and graphs of
      this data are included.

PMID- 16900392
TI  - Benign breast diseases.
AB  - Benign breast diseases have always been neglected in comparison to cancer,
      despite the fact that there are many more patients with such diseases than
      patients presenting to a breast clinic for cancer. Like normal breast tissues,
      benign breast diseases are under a complex system of controls by both systemic
      hormonal and local factors. In this review, we attempt to present an overview of
      the latest knowledge concerning the epidemiology, classification, clinical
      presentation, management, and physiopathology of these disorders.

PMID- 16900393
TI  - Multifaceted role of Rho proteins in angiogenesis.
AB  - The Rho family of GTPases is part of the Ras superfamily. The Rho, Rac, and Cdc42
      members of the family are present in mammalian cells and have been the subject of
      attention of researchers due to their vast spectrum of functions. Rac 1, Cdc42,
      and RhoA are well-known for their role in the regulation of the actin
      cytoskeleton in promoting the formation of lamellipodia, filopodia, and stress
      fibers, respectively. The Rho proteins also participate in the control of cell
      growth, motility, cell-cell adhesions, morphogenesis, cytoskeletal dynamics, and
      cellular trafficking. The mechanisms for eliciting these functions have become
      clearer during the last decade. Concordant with their roles in multiple processes
      of cellular control, the Rho proteins have been shown to be involved in tumor
      growth, progression, metastasis, and now angiogenesis.

PMID- 16900395
TI  - Hypercholesterolemia abrogates an increased resistance of diabetic rat hearts to
      ischemia-reperfusion injury.
AB  - Both, diabetes mellitus (DM) and hypercholesterolemia (HCH) are known as risk
      factors of ischemic heart disease, however, the effects of experimental DM, as
      well as of HCH alone, on ischemia/reperfusion-induced myocardial injury are not
      unequivocal. We have previously demonstrated an enhanced resistance to ischemia
      induced arrhythmias in rat hearts in the acute phase of DM. Our objectives were
      thus to extend our knowledge on how DM in combination with HCH, a model that is
      relevant to diabetic patients with altered lipid metabolism, may affect the size
      of myocardial infarction and susceptibility to arrhythmias. A combination of
      streptozotocin (STZ; 80 mg/kg, i.p.) and the fat-cholesterol diet (1%
      cholesterol, 1% coconut oil; FCHD) was used as a double-disease model mimicking
      DM and HCH simultaneosly occurring in humans. Following 5 days after STZ
      injection and FCHD leading to increased blood glucose and cholesterol levels,
      anesthetized open-chest diabetic, diabetic-hypercholesterolemic (DM-HCH) and age
      matched control rats were subjected to 6-min ischemia (occlusion of LAD coronary
      artery) followed by 10 reperfusion to test susceptibility to ventricular
      arrhythmias in the in vivo experiments and to 30-min ischemia and subsequent 2-h
      reperfusion for the evaluation of the infarct size (IS) in the Langendorff
      perfused hearts. The incidence of the most life-threatening ventricular
      arrhythmia, ventricular fibrillation, was significantly increased in the DM-HCH
      rats as compared with non-diabetic control animals (100% vs. 50%; p<0.05).
      Likewise, arrhythmia severity score (AS) was significantly higher in the DM-HCH
      rats than in the controls (4.9+/-0.2 vs. 3.5+/-0.5; p<0.05), but was not
      increased in the diabetic animals (AS 3.7+/-0.9; p>0.05 vs. controls). Diabetic
      hearts exhibited a reduced IS (15.1+/-3.0% of the area at risk vs. 37.6+/-2.8% in
      the control hearts; p<0.05), however, a combination of DM and HCH increased the
      size of myocardial infarction to that observed in the controls. In conclusion,
      HCH abrogates enhanced resistance to ischemia-reperfusion injury in the diabetic
      rat heart.

PMID- 16900396
TI  - Testing for the presence of magnetite in the upper-beak skin of homing pigeons.
AB  - We carried out magnetic and nonmagnetic experiments on fresh, upper-beak skin
      tissue samples isolated from six pairs of homing pigeons to test whether the
      tissue contains magnetite particles. Results of (1) room-temperature isothermal
      remanent magnetization (IRM) acquisition and alternating field (AF)
      demagnetization, (2) low-temperature demagnetization of saturation IRM acquired
      at 5 K in a field of 5 tesla (T) (SIRM(5 K)) after zero-field cooled (ZFC) and
      field cooled (FC) treatments, and (3) cycling of the saturation IRM acquired at
      300 K in a field of 5 T (SIRM(300 K)) between 5 and 300 K, indicate the presence
      of magnetite in the measured samples. A significant loss of SIRM(5 K) below 20 K
      suggests the dominance of superparamagnetic (SPM) particles. The SIRM acquisition
      capacity of the female pigeon is stronger than that of the male pigeon in all
      four measured pairs, suggesting for the first time that the magnetite
      concentration is probably sex dependent. Light microscopic observation on the
      histological sections stained with Prussian Blue detected the presence of some
      tiny, dotted, dark-blue staining Fe3+ aggregates (size 1-4 microm) located
      directly beneath the subcutis within strands of connective tissue, nearby the rim
      of the regions full of red nuclei. The results of this study support the idea
      that homing pigeons may have a magnetite-based receptor, which potentially could
      be used for sensing the Earth's magnetic field during navigation.

PMID- 16900397
TI  - Protective role of L-ascorbic acid on antioxidant defense system in erythrocytes
      of albino rats exposed to nickel sulfate.
AB  - In this experimental study, we investigated whether L-ascorbic acid has any
      influence on the blood antioxidant defense system, lipid peroxidation and
      hematological parameters of the albino rats exposed to nickel sulfate(NiSO4).
      Twenty four adult rats were divided into four groups of six animals in each
      group. The control rats were untreated and comprised Group I. Group II rats were
      administered nickel sulfate (2.0 mg/100 g b.wt.; intraperitonially, i.p.). Group
      II rats were treated orally L-ascorbic acid (50 mg/100 g b.wt.) and Group IV rats
      were given both nickel sulfate and L-ascorbic acid simultaneously on alternate
      days until the tenth dose. The hematological parameters were assessed: red blood
      corpuscle counts, packed cell volume %, hemoglobin concentration, white blood
      corpuscle counts and platelets count decreased significantly and clotting time
      increased significantly in nickel treated rats. We also observed increase
      malondialdehyde (MDA) and decrease glutathione level (GSH) in erythrocytes of
      nickel treated rats. The activities of erythrocyte antioxidant enzymes like
      superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT)
      were significantly increased in rats treated with nickel sulfate. Simultaneously
      treatment of L-ascorbic acid exhibited a possible protective role on the toxic
      effect of nickel sulfate on the hematological values, erythrocyte MDA and GSH
      concentrations as well as antioxidant enzymatic defense system.

PMID- 16900398
TI  - The overexpression of NADPH-producing enzymes counters the oxidative stress
      evoked by gallium, an iron mimetic.
AB  - Gallium (Ga), an iron (Fe) mimetic promoted an oxidative environment and elicited
      an antioxidative response in Pseudomonas fluorescens. Ga-stressed P. fluorescens
      was characterized by higher amounts of oxidized lipids and proteins compared to
      control cells. The oxidative environment provoked by Ga was nullified by
      increased synthesis of NADPH. The activity and expression glucose 6-phosphate
      dehydrogenase (G6PDH) and isocitrate dehydrogenase-NADP (ICDH) were stimulated in
      Ga-cultures. The induction of isoenzymes of these dehydrogenases was also evident
      in the Ga-stressed cells. Although superoxide dismutase (SOD) activity was
      significantly enhanced in Ga-stressed cultures, catalase activity experienced a
      marked diminution. Fe metabolism appeared to be severely impeded by Ga toxicity.
      This is the first demonstration of the oxidative stress evoked by Ga to be
      neutralized by a reductive environment generated via the overexpression of NADPH
      producing enzymes.

PMID- 16900399
TI  - Pyridine-2,6-bis(thiocarboxylic acid) produced by Pseudomonas stutzeri KC reduces
      chromium(VI) and precipitates mercury, cadmium, lead and arsenic.
AB  - Interactions of the Pseudomonas stutzeri KC siderophore pyridine-2,6
      bis(thiocarboxylic acid) (pdtc) with chromium(VI), mercury(II), cadmium(II),
      lead(II), and arsenic(III) are described. Pdtc was found to reduce Cr(VI) to
      Cr(III) in both bacterial cultures and in abiotic reactions with chemically
      synthesized pdtc. Cr(III) subsequently formed complexes with pdtc and pdtc
      hydrolysis products, and their presence was confirmed using electrospray
      ionization-mass spectrometry (ESI-MS). Cr(III):pdtc complexes were found to
      slowly release Cr(III) as chromium sulfide and possibly Cr(III) oxides. Pdtc also
      formed poorly soluble complexes with Hg, Cd, Pb, and As(III). Hydrolysis of those
      complexes led to the formation of their respective metal sulfides as confirmed by
      energy dispersive X-ray spectroscopy (EDS) elemental analysis. The pdtc-producing
      strain P. stutzeri KC showed higher tolerance to most of these metals as compared
      to a pdtc-negative mutant. A novel role of pdtc is postulated as its involvement
      in providing an extracellular pool of thiols that are used for redox processes in
      detoxification of the bacterial extracellular environment. These redox processes
      can be mediated by transition metal:pdtc complexes.

PMID- 16900400
TI  - Stress response in two strains of the aquatic hyphomycete Heliscus lugdunensis
      after exposure to cadmium and copper ions.
AB  - Biochemical responses to cadmium (Cd2+) and copper (Cu2+) exposure were compared
      in two strains of the aquatic hyphomycete (AQH) Heliscus lugdunensis. One strain
      (H4-2-4) had been isolated from a heavy metal polluted site, the other (H8-2-1)
      from a moderately polluted habitat. Conidia of the two strains differed in shape
      and size. Intracellular accumulation of Cd2+ and Cu2+ was lower in H4-2-4 than in
      H8-2-1. Both strains synthesized significantly more glutathione (GSH), cysteine
      (Cys) and gamma-glutamylcysteine (gamma-EC) in the presence of 25 and 50 microM
      Cd2+, but quantities and rates of synthesis were different. In H4-2-4, exposure
      to 50 microM Cd2+ increased GSH levels to 262% of the control; in H8-2-1 it
      increased to 156%. Mycelia of the two strains were analysed for peroxidase,
      dehydroascorbate reductase, glutathione reductase and glucose-6-phosphate
      dehydrogenase. With Cd2+ exposure, peroxidase activity increased in both strains.
      Cu2+ stress increased dehydroascorbate reductase activity in H4-2-4 but not in H8
      2-1. Dehydroascorbate reductase and glucose-6-phosphate dehydrogenase activities
      progressively declined in the presence of Cd2+, indicating a correlation with
      Cd2+ accumulation in both strains. Cd2+ and Cu2+ exposure decreased glutathione
      reductase activity.

PMID- 16900401
TI  - One-year change in repetitive behaviours in young children with communication
      disorders including autism.
AB  - Repetitive behaviours are a relatively neglected area of study in autism.
      Previous research has concluded that repetitive behaviour is inversely related to
      ability and that it tends to increase over the preschool years. One-hundred and
      four children ages 24-48 months, with autism, autism spectrum disorder (ASD) or
      other disorders, were followed for 13 months. Twelve items from the Autism
      Diagnostic Interview (ADI-R) were analysed, as well as diagnostic algorithm
      scores. Ability was related to degree of repetitive behaviours, except for one
      cluster of relatively able children. ADI-R repetitive behaviour algorithm scores
      increased over time; however, when all 12 behaviours were considered, there was a
      general decrease in impact upon the child's and family's activities. Reasons for
      this decrease are discussed.

PMID- 16900402
TI  - Brief report: error pattern in an autistic savant calendar calculator.
AB  - Special ability in computing the day of the week from given dates was observed in
      a 18 years old male, L.E., suffering from autism. Neuropsychological testing
      revealed severe deficits in all cognitive domains and poor explicit knowledge of
      calendar structure. The subject scored well above the chance level on dates of
      the past and future decades. Error rate and response latency increased with
      temporal remoteness of dates. Most of errors were in indicating the weekday
      before or after that of date stimulus. The performance and error pattern suggest
      that L.E. used "encapsulated" computation algorithm(s) for the day of week task.

PMID- 16900403
TI  - Using virtual environments for teaching social understanding to 6 adolescents
      with autistic spectrum disorders.
AB  - Six teenagers with Autistic Spectrum Disorders (ASDs) experienced a Virtual
      Environment (VE) of a cafe. They also watched three sets of videos of real cafes
      and buses and judged where they would sit and explained why. Half of the
      participants received their VE experience between the first and second sets of
      videos, and half experienced it between the second and third. Ten naive raters
      independently coded participants' judgments and reasoning. In direct relation to
      the timing of VE use, there were several instances of significant improvement in
      judgments and explanations about where to sit, both in a video of a cafe and a
      bus. The results demonstrate the potential of Virtual Reality for teaching social
      skills.

PMID- 16900404
TI  - Developmental correlates of different types of motor imitation in young children
      with autism spectrum disorders.
AB  - This study used a concurrent correlational design to examine associations between
      three types of motor imitation with objects and three proposed correlates in 32
      two- and three-year-old children diagnosed with ASD. Attention-following and fine
      motor ability were significant, unique correlates of imitation in an
      observational learning context. Attention-following was a significant correlate
      of imitation in a direct elicitation context. Social reciprocity was a
      significant correlate of imitation in an interactive play context. These
      associations were observed after controlling for general developmental level.
      Results support previous findings that motor imitation may not reflect a unitary
      construct for children with ASD and that different skills may underlie the
      performance of different types of motor imitation. Implications for interventions
      targeting motor imitation are discussed.

PMID- 16900405
TI  - Effect of cultivar, year grown, and cropping system on the content of tocopherols
      and tocotrienols in grains of hulled and hulless barley.
AB  - In a three-year period (2000-2002) total tocols (tocopherols and tocotrienols),
      content of vitamin E and its isomers (alpha-, beta+gamma-, delta-tocopherols and
      tocotrienols) were assessed in grain of 13 barley genotypes. The highest content
      of tocols (60.3-67.6 mg kg(-1)) and content of vitamin E (Vitamin E equivalent
      18.0-20.1 mg kg(-1)) were determined in the waxy varieties Wanubet, Wabet, and
      Washonubet. Standard varieties, i.e. of a malting type (Krona and Kompakt), had
      statistically significantly lower content of tocols (49.9 and 53.6 mg kg(-1)) and
      vitamin E (15.7-16.1 mg kg(-1)) compared to the waxy varieties. The hulless waxy
      variety Washonubet had statistically significantly higher total content of tocols
      (67.6 mg kg(-1)) and alpha- tocotrienols isomer (42.1 mg kg(-1)) versus all other
      genotypes in the set. Chemical treatment and fertilization statistically
      significantly increased the content of tocols (by 4.7 mg kg(-1)), vitamin E (by
      1.9 mg kg(-1)), isomer alpha-tocopherol (by 0.9 mg kg(-1)) and isomer alpha-
      tocotrienols (by 3.3 mg kg(-1)). The average values of alpha-tocopherols and
      alpha-tocotrienols in the set were 6.7 mg kg(-1) and 29.7 mg kg(-1),
      respectively. Some of the reciprocal lines created by us from the malting and
      waxy varieties are suitable for food use for high contents of all tocopherols and
      alpha-tocotrienols.

PMID- 16900406
TI  - How substance use differs among American secondary schools.
AB  - The purpose of this study was to examine (1) the extent to which student drug use
      and related measures vary among American secondary schools, and (2) how substance
      use varies among schools by certain school characteristics. Data come from the
      Monitoring the Future project's annual surveys of nationally representative
      samples of 8th-, 10th-, and 12th-grade students from 1991 to 2002. The results
      show that the preponderance of variance in drug use and related variables lies
      within schools; only a relatively small amount of variance is between schools.
      Although the variance lies primarily within schools, there remain important
      school-to-school differences in the extent to which students are exposed to drug
      use. The analyses of school characteristics show that schools do indeed differ in
      drug use by their students, particularly by school type, socioeconomic status,
      and race/ethnicity. Eighth and 10th grade (but not 12th grade) students in public
      schools are more likely to be cigarette smokers than students in private schools.
      Students in public middle schools are at higher risk for use of alcohol and
      marijuana; however, among 12th graders, students in Catholic schools are at
      higher risk. School size is generally unrelated to substance use, with few
      exceptions. For the most part, there is a negative association between school
      socioeconomic status and student substance use among 8th graders; but by 12th
      grade, the association tends to be positive or not significant. Racial/ethnic
      composition is significantly associated with student substance use, with majority
      African American schools typically showing the lowest rates of use at all grades.

PMID- 16900408
TI  - Does systems integration affect continuity of mental health care?
AB  - Continuity of care is a concern for mental health clients in the post
      deinstitutionalization era of community care. A proposed solution is systems
      integration. This paper reviewed research on systems integration, focusing on
      continuity of care outcomes. A positive association between systems integration
      and client continuity of care was consistently demonstrated. Better results were
      obtained in systems characterized by stronger management arrangements, fewer
      service sectors, and system wide implementation of intensive case management and
      centralized access to services. Future research should evaluate a wider range of
      systems integrating mechanisms, using client-based measures that more directly
      represent continuity of care experiences.

PMID- 16900407
TI  - Weekly administration of folic acid and epidemiology of neural tube defects.
AB  - OBJECTIVE: In 1999, a folic acid campaign for prevention of neural tube defects
      was started in Nuevo Leon, Mexico, with the recommendation of taking a 5000 -mcg
      tablet of folic acid per week. The purpose of this study was to compare the
      epidemiology of neural tube defects after four years of the campaign. METHODS:
      Cases of anencephaly, spina bifida, and encephalocele (ICD Q00, Q01, Q05, 10th
      Ed.) from public and private hospitals were registered by immediate notification,
      death certificates, and fetal death registries. Comparisons of neural tube
      defects rates, phenotype distribution of cases, and sex ratios, registered before
      and after the folic acid campaign, were done using the Student's t Test and Chi
      square test. RESULTS: There was a 50% reduction in the incidence of anencephaly
      and spina bifida cases from 93 in 1999 (1.04x1000) to 46 in the year 2003
      (0.56x1000) (p<0.001). Spina bifida cases declined up to 70% in 2002 and
      anencephaly cases up to 50% in 2003. In 1999, overall, the ratio (females: males)
      was 0.66 with female excess; the sex ratio was similar for anencephaly and spina
      bifida cases. In the year 2000, female cases showed a significant reduction for
      both spina bifida and anencephaly (75% and 56% respectively); the sex ratio was
      0.57 with a greater male excess for both phenotypes. CONCLUSIONS: Weekly
      administration of 5000 mcg of folic acid reduces the incidence of neural tube
      defects 50%, primarily spina bifida, with a higher reduction of female cases.

PMID- 16900409
TI  - Monitoring of in vitro fat digestion by electron paramagnetic resonance
      spectroscopy.
AB  - PURPOSE: The distribution of drugs between water, oil and mixed micelles after
      the oral application of lipid-based drug delivery systems affects their
      absorption rate. Since it has not been previously possible to monitor this
      process online during in vitro lipolysis, it was our aim to develop a suitable
      real-time method. MATERIALS AND METHODS: To follow the fate of a co-administered
      drug during fat digestion, the spin probe tempol benzoate was incorporated as a
      lipophilic model drug into a long-chain triglyceride (olive oil) and an in vitro
      digestion test was combined with electron paramagnetic resonance (EPR)
      spectroscopy (X-Band). Additionally the progression of digestion was determined
      by means of high performance thin layer chromatography (HPTLC). RESULTS: The
      spectral shape of the EPR spectrum changed significantly during the digestion
      process. EPR spectra at all times could be simulated with three species
      indicating a redistribution of the lipophilic model drug between olive oil,
      phosphate buffer and mixed micelles formed by bile salts and phospholipids.
      CONCLUSION: This in vitro real-time analysis could be a very helpful tool to
      monitor the digestibility of novel lipid-based drug nanocarriers which is an
      important step to optimize and to predict drug delivery processes. In future the
      EPR monitoring of fat digestion will be transferred to in vivo experiments.

PMID- 16900410
TI  - Characterisation of a carrier-free dry powder aerosol formulation using inertial
      impaction and laser diffraction.
AB  - PURPOSE: The purpose of the study was to examine the suitability of using laser
      diffraction to measure the fine particle fraction (FPF) of drugs emitted from
      carrier-free dry powder aerosol formulations. MATERIALS AND METHODS: Particle
      size distribution of terbutaline sulphate from Bricanyl Turbohaler, which
      contained loose agglomerates of drug particles only, was measured separately by
      laser diffraction apparatus equipped with a metal throat and a twin-stage, multi
      stage liquid impingers, or Andersen cascade impactor at flow rates ranging from
      28.3 to 100 l min(-1). In-line measurements were then conducted which allowed the
      same aerosolised particles to be measured first by laser diffraction then
      captured by an impactor or impinger for subsequent chemical analysis. RESULTS: A
      significant linear correlation (p < 0.001, R2 = 0.96, ANOVA) existed between the
      results obtained from two techniques when measurements were conducted
      independently. There was little difference in FPFs measured by inertial impaction
      and laser diffraction at the same flow rate. When in-line measurements were
      conducted, the FPFs measured by inertial impaction were approximately 0.7-0.9
      times the aerosol FPFs measured by laser diffraction. This linear relationship
      was statistically significant and had a statistically insignificant y-intercept,
      regardless of inhaler batches, impinger types and measuring position of the laser
      beam. CONCLUSION: Laser diffraction could prove to be a reliable technique for
      development, evaluation and quality control of carrier-free, dry powder aerosol
      formulations.

PMID- 16900411
TI  - Correlation between inertial impaction and laser diffraction sizing data for
      aerosolized carrier-based dry powder formulations.
AB  - PURPOSE: The purpose of the study was to determine whether the drug fine particle
      fraction (FPF) from different dry powder aerosol formulations measured by laser
      diffraction at a range of flow rates correlated with that measured by inertial
      impaction. MATERIALS AND METHODS: Ten binary formulations were prepared
      containing 1.5% w/w salbutamol base or sulphate, blended with the sieved (63-90
      microm) fraction of different sugars (regular lactose, spray-dried lactose,
      sorbitol, dextrose or maltose). A further six ternary formulations were prepared
      containing 1.5% w/w salbutamol sulphate, 97% coarse lactose (63-90 microm) and
      1.5% micronised or intermediate-sized lactose (1-50 microm). The FPF particles (<
      5 microm) of these formulations were measured by laser diffraction and inertial
      impaction at flow rates between 28.3 and 100 l min(-1). RESULTS: When only the
      particles with diameter < 60 microm obtained by laser diffraction were considered
      the FPF (< 5 microm) could be determined and this enabled the aerosolisation of
      all 16 blends to be feasibly compared at flow rates ranging from 28.3 to 100 l
      min(-1). A significant linear correlation was found between the fine fractions
      measured by laser diffraction and the salbutamol fine fractions determined by
      inertial impaction (r2 = 0.934). Such correlation was also confirmed for
      formulations containing added fine lactose. CONCLUSION: Particle size measured by
      laser diffraction under the employed conditions reflected the aerodynamic
      properties of the drug. Laser diffraction can be used as on-, in- and/or at-line
      measurements and controls for dry powder aerosol formulations.

PMID- 16900412
TI  - Activity-based rate-adaptive pacemakers under hyperbaric conditions.
AB  - OBJECTIVES: The aim of this study was to test a variety of currently available
      activity-based rate-adaptive pacemakers under hyperbaric conditions. BACKGROUND:
      Sports divers with pacemakers can dive under certain circumstances. The rate
      response of activity-sensing pacing under hyperbaric conditions has rarely been
      evaluated. MATERIALS AND METHODS: We manufactured a miniaturized hyperbaric
      chamber. A pacemaker inside was kept close to the corresponding telemetry wand
      placed on top of the chamber. An inflation device for coronary balloon
      angioplasty was used to create hydraulic pressure. Group I pacemakers were
      exposed to a 30 msw/98 fsw/4 ATA and after a 1-month waiting period to 60 msw/197
      fsw-depth/7 ATA. Group II was exposed to only one dive to 60 msw. The electrogram
      and event marker telemetry were used to monitor the pacing stimuli and
      measurements were made for case distortion. RESULTS: The baseline pacing rate did
      not change in 27 tests. Return to baseline was shown during 18 tests after
      transient sensor-driven rate. There was a sensor rate response to manual brief
      shaking during and following testing. A case distortion was shown in 15 of 29
      tests at 60 m. CONCLUSIONS: Modern accelerometers showed no sensitivity to
      pressure on the pacemaker can at 30 msw/98 fsw and 60 msw/197 fsw but in some
      devices responded to pressure changes. There was no pacing dysfunction or
      suppression of the sensor response despite the high incidence of case distortion
      at 60 msw/197 fsw. As a general rule, diving should not be allowed at depths
      greater than 20 msw/65 fsw.

PMID- 16900413
TI  - The effects of childhood trauma on sex trading in substance using women.
AB  - This article presents a model developed to understand the relationship between
      childhood victimization, perpetration of violence, and later cocaine dependence
      and adult sex trading among drug using women. A cohort of heavy drinking and drug
      using women (N=594) recruited for two on-going community based HIV prevention
      studies in St. Louis City was analyzed to evaluate this association using path
      analysis. The women were stratified into two groups: sex traders and non-sex
      traders. Sex traders were more likely than non-sex traders to report being forced
      to kiss or touch someone in a sexual way before age 15 (35% vs. 22%), being
      kissed or touched in a sexual way by others when they did not want to be (42% vs.
      31%), and being forced to have sexual intercourse (30% vs. 21%). Sex traders were
      more likely than non-sex traders to use a weapon or threaten someone with a
      weapon (29% vs. 18%) and physically hurt others on purpose before age 15 (9% vs.
      5%). Path analysis confirmed that childhood victimization had a significant and
      direct association with both adult cocaine dependence and sex trading. However,
      the association between childhood perpetration and adult sex trading was mediated
      by cocaine dependence. This analysis concludes that childhood victimization was
      the strongest predictor of cocaine dependence and sex trading in adulthood.

PMID- 16900414
TI  - Exhibitionistic and voyeuristic behavior in a Swedish national population survey.
AB  - We examined the prevalence and correlates of self-reported sexual arousal from
      exposing one's genitals to a stranger (exhibitionistic behavior) and spying on
      others having sex (voyeuristic behavior) in a representative national sample. In
      1996, 2,450 randomly selected 18-60 year-olds from the general population of
      Sweden were interviewed in a broad survey of sexuality and health. A total of 76
      (3.1%) respondents reported at least one incident of being sexually aroused by
      exposing their genitals to a stranger and 191 (7.7%) respondents reported at
      least one incident of being sexually aroused by spying on others having sex.
      Exhibitionistic and voyeuristic behaviors were examined for possible associations
      with 9 sociodemographic, 5 health, 4 risk-taking, and 17 sexuality variables.
      Both paraphilia-like behaviors were positively associated with being male and
      having more psychological problems, lower satisfaction with life, greater alcohol
      and drug use, and greater sexual interest and activity in general, including more
      sexual partners, greater sexual arousability, higher frequency of masturbation,
      higher frequency of pornography use, and greater likelihood of having had a same
      sex sexual partner. Consistent with previous research in clinical samples of men
      with paraphilias, respondents who reported either exhibitionistic or voyeuristic
      behavior had substantially greater odds of reporting other atypical sexual
      behavior (sadomasochistic or cross-dressing behavior). There was evidence both
      for general and specific associations between sexual fantasies and their
      corresponding paraphilia-like behaviors. The implications of these findings for
      research on atypical sexual interests, atypical sexual behavior, and paraphilias
      are discussed.

PMID- 16900415
TI  - The sexual excitation/sexual inhibition inventory for women: psychometric
      properties.
AB  - This article reports on the development of a new questionnaire designed to assess
      the propensity for sexual excitation and sexual inhibition in women: The Sexual
      Excitation/Sexual Inhibition Inventory for Women (SESII-W). The theoretical model
      underlying this research, the Dual Control Model, postulates that sexual response
      depends on a balance between excitatory and inhibitory mechanisms and that
      individuals vary in their propensity for excitation and inhibition. This study
      describes the development and initial validation of the SESII-W in a sample of
      655 women (M age, 33.9 years). Factor analysis identified eight factors and two
      higher-order factors: one related to sexual excitation and one to sexual
      inhibition. The measure demonstrated good test-retest reliability and
      discriminant and convergent validity. Our data underscore that a number of
      factors affect women's sexual arousal and these appear to be related to opposing
      processes of sexual excitation and sexual inhibition. Theoretical issues,
      possible gender differences, and the value of using qualitative data to inform
      questionnaire development are discussed.

PMID- 16900416
TI  - Regret after sex reassignment surgery in a male-to-female transsexual: a long
      term follow-up.
AB  - This case report describes a four-decade presentation of a non-homosexual gender
      dysphoric male patient. The case material was collected from two main sources.
      One of the authors had weekly therapy sessions with the patient over a period of
      2 years almost 15 years after sex reassignment surgery. Information was also
      gained from the patient's medical records covering the period from the early
      1960s to the early 1990s. Over the years, the patient fulfilled the criteria for
      different diagnoses: overanxious reaction of childhood, fetishism and
      transvestism during adolescence, and transsexualism during adolescence and early
      adulthood. The purpose of this report was to shed light on aspects of regret, its
      manifestation in a male-to-female transsexual with psychiatric co-morbidity, and
      to show the complexity of the process of adjustment when regret is involved. The
      present case is an argument for a strict interpretation of the Standards of Care
      provided by the Harry Benjamin International Gender Dysphoria Association in
      terms of evaluating patients' mental health, apart from the evaluation of the
      gender identity disorder, and the patients' subsequent need for treatment
      interventions.

PMID- 16900417
TI  - Optimal design of small-diameter silicone chest drain devices.
AB  - To overcome the complications due to the use of noncompliant large diameter
      conventional chest drain devices, a flexible small diameter chest drain device
      was designed and simulated based on computational fluid dynamics (CFD)
      techniques. It was clearly shown that the pressure drop and velocity increase of
      the most distal drainage holes, which are located near the suction end, are
      dominant over other drainage holes. A conventional chest drain device with
      circular side holes showed higher mass flow rate due to larger cross sectional
      area. It also showed less dependency on the side hole placement compared to open
      channel, closed cavity chest drain with rectangular side holes. When all holes
      are opened the conventional chest drain showed 6% increase in flow rate while the
      open channel, closed cavity drain device showed 47% increase in flow rate
      reflecting a better design performance. These results provide an insight into the
      CFD-based optimal design of chest drain devices for potential applications in
      clinical intraoperative procedures.

PMID- 16900418
TI  - Hemodynamic analysis and design of a paracorporeal artificial lung device.
AB  - We have extended our model of the ovine pulmonary circulation to include a model
      of a paracorporeal artificial lung (AL) and its attachments to the natural
      pulmonary circulation in two configurations: in series and in parallel. Our model
      of the natural lung (NL) circulation is first shown to be in agreement with
      hemodynamic and input impedance data from the open literature. We then study
      design efficacy of the AL in terms of its housing and attachments. A sensitivity
      analysis of the modified pulmonary circulation model reveals that there are three
      key parameters: inlet graft length (IGL) and the compliances of the inlet
      compliance chamber (CC) and housing of the artificial lung. Based on literature
      reports, we assume the right ventricle is well-matched to the impedance of the
      natural pulmonary circulation and adjust the parameters of the modeled AL circuit
      to achieve the best least-squares fit to natural pulmonary input impedance data.
      Best-fit parameters produce impedance curves that fit natural impedance well,
      particularly below 3 Hz, where both compliance and graft length have their
      largest effects. Of these parameters, the impedance profile is most sensitive to
      IGL. However, the compliances are important, as well, particularly at low
      frequencies.

PMID- 16900420
TI  - An implantable aortic valvo-pump for destination therapy.
AB  - To investigate the possibility of a long-term applicable left ventricular assist
      device, a 23 mm outer diameter and 31 g weight implantable aortic valvo-pump was
      developed. It consists of a rotor and a stator; the rotor has a driven magnets
      assemble and an impeller, the stator has a motor coil with iron core and a
      outflow guide vane. The device locates the position of aortic valve, delivers the
      blood directly from left ventricle to aorta. Neither connecting conduits nor
      "bypass" circuits are necessary. Therefore, the device has promisingly better
      antithrombogenicity than other heart pumps. In hemodynamic testing, the pump can
      produce a blood flow of 7 l/min volume with 50 mmHg pressure increase at 15,000
      rpm rotating speed, and at zero flow rate the pump can maintain a diastolic
      pressure over 80 mmHg at same rotating speed. For further studies the blood
      compatibility and the durability of the device are of most importance.

PMID- 16900419
TI  - Assessment of left ventricular viscoelastic components based on ventricular
      harmonic behavior.
AB  - BACKGROUND: Assessment of left ventricular (LV) function with an emphasis on
      contractility has been a challenge in cardiac mechanics during the recent
      decades. The LV function is usually described by the LV pressure-volume (P-V)
      relationship. Based on this relationship, the ratio of instantaneous pressure to
      instantaneous volume is an index for LV chamber stiffness. The standard P-V
      diagrams are easy to interpret but difficult to obtain and require invasive
      instrumentation for measuring the corresponding volume and pressure data. In the
      present study, we introduce a technique that can estimate viscoelastic
      properties, not only the elastic component but also the viscous properties of the
      LV based on oscillatory behavior of the ventricular chamber and it can be applied
      non-invasively as well. MATERIALS AND METHODS: The estimation technique is based
      on modeling the actual long axis displacement of the mitral annulus plane toward
      the cardiac base as a linear damped oscillator with time-varying coefficients.
      Elastic deformations resulting from the changes in the ventricular mechanical
      properties of myocardium are represented as a time-varying spring while the
      viscous components of the model include a time-varying viscous damper,
      representing relaxation and the frictional energy loss. To measure the left
      ventricular axial displacement ten healthy sheep underwent left thoracotomy and
      sonomicrometry transducers were implanted at the apex and base of the LV. The
      time-varying parameters of the model were estimated by a standard Recursive
      Linear Least Squares (RLLS) technique. RESULTS: LV stiffness at end-systole and
      end-diastole was in the range of 61.86-136 dyne/gxcm and 1.25-21.02 dyne/gxcm,
      respectively. Univariate linear regression was performed to verify the agreement
      between the estimated parameters, and the measured values of stiffness. The
      averaged magnitude of the stiffness and damping coefficients during a complete
      cardiac cycle were estimated as 58.63+/-12.8 dyne/gxcm and 0 dynexs/gxcm,
      respectively. CONCLUSION: The results for the estimated elastic coefficients are
      consistent with the ones obtained from force-displacement diagram. The trend of
      change in the estimated parameters is also in harmony with the previous studies
      done using P-V diagram. The only input used in this model is the long axis
      displacement of the annulus plane, which can also be obtained non-invasively
      using tissue Doppler or MR imaging.

PMID- 16900421
TI  - On the definition and measurement of human scent: comments on Curran et Al.

PMID- 16900423
TI  - Olfaction and identification of unrelated individuals: examination of the
      mysteries of human odor recognition.
AB  - Although several studies have examined the effect of human odor on kin
      recognition and mate choice, few have focused on the impact of familiarity on
      recognition of nonrelatives by olfactory cues. As part of a program designed to
      engage students in scientific research, 53 high school students researched,
      planned, and implemented a project to analyze the effect of odor on human
      recognition of, and preference for, friends, sex, and self. A total of 37
      students, including friends of their choosing, wore T-shirts for three
      consecutive nights. During that time, subjects were controlled for exposure to
      extraneous perfumes, household odors, and other humans. The students were then
      asked to smell a series of five shirts and evaluate them with respect to
      pleasantness. Students were also asked to identify the shirts belonging to
      themselves and their friend, and determine the sex of the person who wore each
      shirt. Although subjects were unable to distinguish sex by olfactory cues alone,
      a significant percentage of subjects were able to identify their own odor
      (51.6%), as well as distinguish the odor cue of their friend (38.7%).
      Additionally, subjects who could not identify their friend's cue were apt to
      choose the odor of a member of the opposite sex as their friend. This result was
      not believed to rely on odor preference as neither individual, friend, nor
      stranger odors were rated significantly different with respect to odor
      pleasantness. The ability to recognize friends via odor cues lends credence to
      the hypothesis that association and familiarity are important aspects of
      conspecific olfactory recognition in humans. Furthermore, this study augments
      evidence that olfaction may supplement visual and auditory cues used in human
      conspecific and kin recognition.

PMID- 16900424
TI  - (1S)-1-ethyl-2-methylpropyl 3,13-dimethylpentadecanoate: major sex pheromone
      component of Paulownia bagworm, Clania variegata.
AB  - The Paulownia bagworm, Clania variegata Snell. (Lepidoptera: Psychidae), is one
      of the most significant forest defoliators in China. In gas chromatographic (GC)
      electroantennographic detection analyses of pheromone gland extracts of female C.
      variegata on three GC columns (DB-5, DB-23, DB-210), two compounds (A and B)
      elicited strong responses from male antennae. The more abundant component B was
      isolated by high-performance liquid chromatography and identified as 1-ethyl-2
      methylpropyl 3,13-dimethylpentadecanoate by transesterification, GC-mass
      spectrometry (MS), and comparison of its spectral and GC retention
      characteristics with those of synthetic compounds. In field trapping experiments
      in China, racemic and (1S)-1-ethyl-2-methylpropyl 3,13-dimethylpentadecanoate
      [but not the (1R)-stereoisomer] attracted male C. variegata. The absolute
      configuration of B (a molecule with three chiral centers) and the structure of
      component A remain to be determined.

PMID- 16900425
TI  - Characterization of a female-produced courtship pheromone in the parasitoid
      Nasonia vitripennis.
AB  - Males of the parasitoid Nasonia vitripennis (Walker) (Hymenoptera: Pteromalidae)
      show a characteristic courtship behavior. We demonstrate that male arrestment and
      key behavioral elements of the courtship sequence are mediated by a female
      derived contact sex pheromone. Males were arrested on paper disks treated with
      female extracts but not on those treated with male extracts. Male responsiveness
      was influenced by the surface to which female extracts were applied. Extracts
      applied to an extracted beetle elytron arrested males more strongly than those
      applied to filter paper of comparable size. However, more complex behavioral
      elements, such as head nodding and copulation attempts, were shown only when
      extracts were applied to extracted male cadavers, suggesting that tactile or
      visual cues synergize the male response. The chemicals involved are stable, of
      low volatility, and nonpolar. Dead females arrested males and elicited courtship
      behavior for at least 8 d. Males showed no sign of attraction to live females at
      a distance of 3 cm in an olfactometer. Fractionation of female extracts
      demonstrated that the activity was exclusively located in the nonpolar fraction.
      Analysis of the active fraction by gas chromatography-mass spectrometry revealed
      that cuticular hydrocarbons with chain lengths between 25 and 37 carbon units
      were present. Comparison of hydrocarbon profiles from males and females showed
      qualitative and quantitative differences. These results suggest that sex-specific
      cuticular hydrocarbons are the key signals mediating the male courtship behavior
      in N. vitripennis.

PMID- 16900426
TI  - Molecular cloning and in Situ expression patterns of two new pheromone-binding
      proteins from the corn stemborer Sesamia nonagrioides.
AB  - We describe the identification and characterization of two new cDNAs encoding
      pheromone-binding proteins (PBPs) from the male antennae of Sesamia nonagrioides,
      a species where no PBPs have been identified to date. Because PBPs are thought to
      participate in the first step of odor detection in a specific manner, we focused
      our investigation on this olfactory protein family using reverse transcription
      polymerase chain reaction strategies. The deduced amino acid sequences of
      SnonPBP1 and SnonPBP2 revealed mature proteins of 142 and 143 amino acids,
      respectively, with six cysteine residues in conserved positions relative to other
      known PBPs. The alignment of the two mature S. nonagrioides PBPs with other
      noctuid PBPs showed high sequence identity (70-80%) with other full-length
      sequences from GenBank. Sequence identity between SnonPBP1 and SnonPBP2 was only
      46%, suggesting that the two proteins belong to different classes of PBPs already
      described from the Noctuidae. Furthermore, analyses of expression patterns of
      SnonPBP1 and SnonPBP2 were performed by in situ hybridization on antennae of both
      sexes, and these studies revealed the expression of the two PBPs at the bases of
      olfactory sensilla (basiconica or trichodea) from both sexes. The possible
      binding properties of these two new PBPs are discussed according to their
      homologies with other known PBPs and S. nonagrioides pheromone components.

PMID- 16900427
TI  - Effect of wind speed on the pheromone-mediated behavior of sexual morphs of the
      potato aphid, Macrosiphum euphorbiae (Thomas) under laboratory and field
      conditions.
AB  - The effect of wind on the potato aphid, Macrosiphum euphorbiae, male
      responsiveness to the sex pheromone, and on the calling behavior of virgin
      oviparae, was studied under constant wind speeds in the laboratory and in the
      field. A significant proportion of females called at wind speeds up to 4 m/sec,
      whereas male flight behavior in clean air was inhibited at velocities > 2 m/sec.
      However, males continued to walk over the range of wind speeds at which females
      called. Under constant wind velocities in a wind tunnel, males downwind of
      calling females oriented on the upwind edge of the release stand, and fewer
      individuals took flight at low constant wind speeds than in a clean air plume. In
      all cases, whether calling females were present or not, the males that took
      flight moved downwind. However, when a bridge was available, a significant
      proportion of males walked upwind to the pheromone source. The same orientation
      and walking behaviors were observed when males were placed downwind of calling
      females under variable wind conditions in the field. However, contrary to the
      laboratory results, 30% of the males tested flew upwind and landed on the source.
      A more detailed examination found that males orienting toward a source would walk
      if wind speeds were high but initiated flight in an "upwind" direction if there
      was a lull in wind velocity. These findings suggest that for the potato aphid,
      and probably for many other insect species with weak flight capacity, walking
      behavior is a significant component of pheromone-mediated mate location. This
      would permit males to continue foraging for calling females in the vicinity when
      wind velocities inhibit flight.

PMID- 16900428
TI  - Sustained production of the labile pheromone component, (Z,Z)-6,9-heneicosadien
      11-one, from a stable precursor for monitoring the whitemarked tussock moth.
AB  - The principal sex pheromone component of the whitemarked tussock moth (WMTM),
      Orgyia leucostigma, was recently identified as (Z,Z)-6,9-heneicosadien-11-one
      (Z6Z9-11-one-21Hy). However, it is thermally unstable and quickly degrades under
      field conditions so that baited traps are effective for only one night. We have
      developed a solution to this problem that combines two techniques: (1) the use of
      a stable pheromone precursor, (Z,Z)-6,9-heneicosadien-11-one ethylene ketal,
      which is hydrolyzed to the dienone by an acidic aqueous solution (2% p
      toluenesulfonic acid in 35% aqueous sorbitol), and (2) use of a small, off-the
      shelf, autonomous pump (the Med-e-Cell Infu-disktrade mark) to deliver the
      precursor continuously to a suitable substrate where it is converted rapidly into
      the attractive dienone pheromone component. The pump and hydrolysis substrate fit
      inside sticky traps and because generation and release of pheromone is
      continuous, the instability of the pheromone is not an issue. In
      electroantennogram bioassays, dose-dependent responses were obtained with 1 to
      1000 ng of hydrolyzed ketal on filter paper, but no response was obtained to 1000
      ng of the ketal itself. In wind tunnel bioassays, males were attracted to lures
      emitting the dienone pheromone component generated from 0.1 to 100 ng of the
      hydrolyzed ketal. Field tests in 2004 and 2005 showed that sticky traps fitted
      with the pump delivering the ketal (0.1-1 microg/microL in heptane) at 10
      microL/hr to a cotton pad soaked with the hydrolyzing solution were attractive to
      male WMTM. No moths were caught in controls or traps baited with (Z)-6-heneicosen
      11-one. An average of 0.51 moths per trap night was caught over an 18-night
      period in 2005. The results represent a first step toward developing a sensitive
      and practical monitoring tool for the WMTM by using a ketal precursor of its
      unstable dienone pheromone component.

PMID- 16900429
TI  - Oryctes monoceros trapping with synthetic pheromone and palm material in Ivory
      Coast.
AB  - Oryctes monoceros is the most serious pest in coconut plantations, causing up to
      40% damage in tropical Africa, especially in Ivory Coast. With a view to reducing
      pest populations by olfactory trapping, field trials were carried out to assess
      the efficiency of a synthetic aggregation pheromone: ethyl 4-methyloctanoate (1),
      4-methyloctanoic acid (2), a related volatile produced by males, and decaying
      palm material, either oil palm empty fruit bunches (EFB) or pieces of coconut
      wood (CW) of various ages. Vertical polyvinyl chloride tube traps (2 x 0.16 m
      with two openings in the upper half), embedded in the soil, were more efficient
      than 30-L pail traps 1.5 m above ground. EFB, which were inactive alone,
      synergized captures with synthetic pheromone. CW was more effective than EFB in
      comparative trials. Compound 2 did not catch any beetles when assessed with EFB,
      and reduced catches by 1 + EFB when tested at >10% with the pheromone. Trapping
      over 6 mo in 2002 and 2003 in a 19-ha coconut plot inside a 4,000-ha oil palm
      estate reduced damage from 3.8% in 2001 to 0.5% in 2002, then to 0.2% in 2003.
      Damage was 0.0% in 2004 with routine trapping using 32 traps, which caught 3369
      beetles in 9 mo. The results are discussed in relation to other Dynastid palm
      pests and coconut protection in Ivory Coast.

PMID- 16900430
TI  - Compatible and incompatible Xanthomonas infections differentially affect
      herbivore-induced volatile emission by pepper plants.
AB  - Recent studies have alerted us to the potential for conflicts between pathogen-
      and herbivore-induced plant defenses. The lack of studies on the induced chemical
      changes that simultaneous insect and pathogen attacks have on the host plant has
      become apparent. In the present study, we found that pepper plant volatile
      profiles can be differentially induced by compatible and incompatible bacterial
      infection and beet armyworm (BAW) damage when applied alone or in combination
      upon the same host. We also found that plants under simultaneous compatible
      bacterial and BAW attack are able to produce volatiles in quantities greater than
      those produced by healthy plants in response to BAW feeding. In contrast, plants
      exposed to the incompatible pathogen challenge showed a total volatile release
      below the level of healthy plants exposed to BAW damage. This suppression of BAW
      induced volatiles coincided with increased methyl salicylate production from
      incompatible bacteria-infected plants. Feeding choice experiments revealed that,
      when given a choice, BAW larvae fed significantly more on leaves of plants
      infected with the incompatible bacteria as soon as 2 d after inoculation, while a
      significant increase in insect feeding on the plants infected with the compatible
      bacterial strain was not seen until day 4 after inoculation. Additionally,
      survival for third instars to pupation was significantly higher when feeding on
      infected plants than on healthy plants, regardless of compatibility. These
      results are indicative of lowered herbivore defenses due to disease progression
      on the plants.

PMID- 16900431
TI  - Structural elucidation and biological activity of acyl-homoserine lactones from
      the phytopathogen Pantoea ananatis Serrano 1928.
AB  - In Gram-negative bacteria, the acyl-homoserine lactones (acyl-HSLs) are the main
      signaling substances employed in cell-to-cell communication systems. This paper
      describes the chemical characterization of acyl-HSLs produced by the worldwide
      spread phytopathogen Pantoea ananatis (Serrano 1928) by using gas chromatography
      electron impact mass spectrometry. The absolute configuration of the major
      identified substance, (S)-(--)-N-hexanoyl-HSL, was determined with gas
      chromatography-flame ionization detection with a chiral capillary column.
      Biological activities of extracts, fractions, and synthetic products were
      evaluated with the specific reporter Agrobacterium tumefaciensNTL4(pZLR4) in beta
      galactosidase expression assays.

PMID- 16900432
TI  - Influence of fungal infection and wounding on contents and enantiomeric
      compositions of monoterpenes in phloem of Pinus sylvestris.
AB  - To identify chemical resistant markers induced by fungal or mechanical injury,
      young trees of Scots pine (Pinus sylvestris) were subjected to inoculations of
      blue stain fungi associated with the pine shoot beetles Tomicus piniperda and T.
      minor. Among the 20 trees selected for chemical analyses, 16 were divided into
      four groups: one as control and three were pretreated by wounding only, or by
      inoculation with either the blue stain fungus Leptographium wingfieldii or
      Ophiostoma canum. Four wk after pretreatment, all 16 pretreated trees were mass
      inoculated with L. wingfieldii. The absolute and relative amounts, as well as the
      enantiomeric compositions of monoterpene hydrocarbons in the phloem, were
      determined via a small sample of the phloem before and after the pretreatment and
      mass inoculation, by using two-dimensional gas chromatography (2D GC) and GC-mass
      spectrometry (MS). After mass inoculation, the absolute amounts of most of the
      monoterpenes decreased in the phloem sampled >20 cm from the fungal infection,
      and were higher in the phloem sampled within the infected reaction zone. The
      relative amounts of both (-)-beta-pinene and (-)-limonene increased in phloem
      samples taken >20 cm above the fungal inoculation in the preinoculated trees
      compared with phloem sampled from the remaining four control trees. The
      enantiomeric compositions of beta-pinene and limonene changed, after fungal
      growth, at defined distances from the inoculation site: the proportion of the (-)
      enantiomers was highest in the phloem sampled >20 cm from the fungal inoculation.
      Four wk after pretreatment, monoterpene production in the phloem at the site of
      inoculation was more enhanced by L. wingfieldii than by O. canum. However, the
      different virulence levels of the fungi did not affect the enantiomeric
      composition of the monoterpenes. The biosynthesis of monoterpene enantiomers is
      discussed in relation to induced pathogen resistance.

PMID- 16900433
TI  - Variation of proanthocyanidins in Lotus species.
AB  - The proanthocyanidin (PA) chemistry of 12 Lotus species of previously unknown PA
      content was examined in comparison with agricultural cultivars of L.
      pedunculatus, L. corniculatus, and L. tenuis and a "creeping" selection of L.
      corniculatus. Herbage harvested in winter 2000 and again in spring had
      extractable PA concentrations, estimations of which varied between 0.2 and 10.9%
      of dry matter. The four novel Lotus spp. with the highest concentrations were
      selected for further evaluation together with the agricultural accessions. PA
      concentrations in herbage were estimated for individual plants harvested in
      spring 2001 and bulk samples harvested in summer 2002-2003. PA oligomer and
      polymer fractions were separated by Sephadex LH-20 chromatography from aqueous
      acetone PA extracts of herbage. The chemical characteristics of the fractions
      were examined by acid catalyzed degradation with benzyl mercaptan, (13)C nuclear
      magnetic resonance spectroscopy, electrospray ionization (ESI), and matrix
      assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF
      MS). A wide variation was found in the chemical composition, mean degree of
      polymerization (mDP), and polydispersity of PAs from Lotus spp. Fractions from L.
      americanus, L. corniculatus "creeping selection," and L. pedunculatus consisted
      predominantly of prodelphinidin (PD) units, whereas PA from L. angustissimus and
      L. corniculatus consisted predominantly of procyanidin (PC) units. An
      approximately equal composition in terms of PC and PD units was found in L.
      parviflorus and L. suaveolens. In L. angustissimus, epicatechin is dominant in
      both extender and terminal units. In all Lotus PA fractions, the 2,3-cis isomers
      (epicatechin or epigallocatechin) predominated. Only trace amounts of PA were
      extracted from L. tenuis. The mDP of the PA fractions ranged from 8 to 97, with
      high mDP found only for L. pedunculatus and L. americanus. In the ESI-MS and
      MALDI-TOF-MS of the L. angustissimus PA fraction, ions for homo-PC oligomers were
      dominant, whereas ions for hetero-oligomers predominated in the other Lotus spp.
      Ions indicative of A-type linkages were observed in the MS of L. americanus. The
      results are discussed in terms of possible relationships between the
      concentration and composition of the PAs of Lotus spp. and ecological factors.

PMID- 16900434
TI  - An evaluation of the allelopathic potential of selected perennial groundcovers:
      foliar volatiles of catmint (Nepeta x faassenii) inhibit seedling growth.
AB  - Six perennial groundcovers including Alchemilla mollis, Nepeta x faassenii, Phlox
      subulata, Sedum acre, Solidago cutleri, and Thymus praecox were investigated for
      the allelopathic potential of their respective foliar tissues via evaluation of
      volatile constituents produced by foliage. These groundcovers were selected for
      further laboratory evaluation because of superior performance as weed-suppressive
      groundcovers in previous field experiments. Foliar volatile components of N. x
      faassenii exhibited the strongest inhibitory effects on seedling growth of curly
      cress (Lepidium sativum), but S. cutleri also showed allelopathic potential by
      reducing shoot growth of curly cress seedlings with extracted volatiles. Although
      A. mollis and P. subulata exhibited strong weed-suppressive traits in past field
      experiments, weed suppression is apparently associated with either competition
      for resources or other allelopathic mechanisms rather than an allelopathic effect
      caused by volatiles. Volatiles of N. x faassenii were further evaluated with gas
      chromatography coupled to mass spectrometry (GC-MS). A total of 21 chemical
      constituents were identified in the volatile cocktail; 17 components were
      identified from a direct crude leaf sample extraction, including sabinene, beta
      pinene, beta-myrcene, 2-(2-ethoxyethoxy)-ethanol, 1,8-cineole, ocimene, neryl
      Acetate, 4aalpha,7alpha,7aalpha-nepetalactone, alpha-copaene, trans
      caryophyllene, alloaromadendrene, 4abeta,7alpha,7abeta-nepetalactone, germacrene
      D, beta-farnesene, chi-cadinene, germacrene B, and beta-sesquiphellandrene. Five
      additional constituents were identified in a methanolic extract of dried of N. x
      faassenii foliage, but not the volatile cocktail collected from N. x faassenii
      foliage. These included methyl benzoate, 2,4-decadienal, neryl acetate,
      isodihydronepetalactone, and caryophyllene oxide. Three components, 2-(2
      ethoxyethoxy)-ethanol, alloaromadendrene, and chi-cadinene, were not only
      detected in both the volatile mixture and the methanolic extract, but also in an
      aqueous foliar extract that exhibited potential allelopathic activity.

PMID- 16900435
TI  - Female urethral and bladder neck injury after rape: an appraisal of the surgical
      management.
AB  - The aim of this study was to discuss the surgical management of urethral and
      bladder neck injury after urethral coitus during rape. A 21-year-old lady
      presented with total urinary incontinence of 1-year duration after being raped.
      On examination, she had urethral laceration and a patulous urethra and bladder
      neck suggesting urethral coitus during the rape. Her introitus and vagina were
      however normal. She had repair of her urethral laceration and plication of her
      urethra and bladder neck via a vaginal approach. She regained her continence and
      voids without any residual urine. Urethral coitus is rare. Urethral coitus in the
      presence of a normal introitus and vagina is very rare. The urethral and bladder
      neck injury resulting from this can be satisfactorily corrected by urethral and
      bladder neck plication via a vaginal approach with the vaginal incisions
      positioned to forestall suture line apposition, which may lead to wound failure.

PMID- 16900436
TI  - The relationship of urethral resistance pressure and pressure flow parameters in
      women with lower urinary tract symptoms.
AB  - This prospective study aims to evaluate the relationship between urethral
      resistance pressure (URP) and pressure flow parameters in women with lower
      urinary tract symptoms (LUTS). Consecutive women with LUTS attending three
      tertiary referral urodynamic clinics were asked to undergo urodynamic evaluation,
      pressure flow studies and URP measurement. The pressure flow parameters such as
      detrusor pressures at the start of flow (ODP), detrusor pressure at peak flow
      rate (PdetQmax), peak flow rate (Qmax) and detrusor pressure at the end of flow
      (CDP) were measured. The relationship between URP and pressure flow parameters
      was evaluated as well as differences between each urodynamic group. Two hundred
      seventy-nine women attended for urodynamic investigations. Two hundred twenty
      three (79.9%) women had good quality pressure flow measurements and were included
      in the study. The mean age was 58 years (range 21-83). Women with urodynamic
      stress incontinence had significantly lower URP and ODP than those with detrusor
      over-activity [54.8 (+/-17.9) and 12.4 (+/-4.1) cmH(2)O, respectively, vs 85.6
      (+/-21.4) and 33.7 (+/-13.3) cmH(2)O, respectively) (p<0.05, Bonferroni test).
      Furthermore, women with urodynamic stress incontinence have significantly lower
      PdetQmax values as well as higher Qmax than women with competent urethral
      sphincters (p<0.05, Bonferroni test). There was a significant correlation between
      ODP, PdetQmax, Qmax and URP measurements. In urodynamic stress incontinence, both
      URP and pressure flow parameters are reduced. Although the trend for values of
      both tests were similar and there was a significant correlation between these
      tests, we should consider that urethral function at rest differ from that during
      voiding due to activation of additional mechanisms. Therefore, further study is
      needed to confirm our results.

PMID- 16900437
TI  - Sexual intercourse: an unusual cause of vesicovaginal fistula.
AB  - Voluntary sexual intercourse in an adult woman with normal vagina is not a known
      cause of vesicovaginal fistula (VVF), though sexual abuse or sexual intercourse
      with young girls before reaching physical maturity can result in VVF. Postcoital
      VVF in an adult woman without these predisposing factors is very infrequent. A
      nulliparous woman who had VVF after first intercourse is presented, as it is
      unusual by virtue of etiology.

PMID- 16900438
TI  - Estrogen and ghrelin decrease cytoplasmic expression of p27kip1, a cellular
      marker of ageing, in the striated anal sphincter and levator muscle of
      ovariectomized rats.
AB  - A study was carried out to investigate the effect of estrogen and/or ghrelin on
      the cellular marker of ageing, p27kip1, in pelvic floor muscles of ovariectomized
      rats. Virgin Wistar rats (13 months old) underwent ovariectomy followed (1 month)
      by 42 daily intraperitoneal 17-beta estradiol (10 microg/kg), ghrelin (2
      microg/kg), both hormones, or placebo vehicle (n=6x4 groups). Six more age
      matched animals underwent sham surgery without ovariectomy. Cytoplasmic
      expression of p27kip1 in the striated urethral and anal sphincters and levator
      muscle was measured by Western blot analysis in all animals (n=30). p27kip1
      signal intensity significantly increased postovariectomy in all muscles compared
      to sham animals. In the anal sphincter and levator, signal intensity decreased to
      sham levels with ghrelin or estrogen and decreased further after estrogen or
      ghrelin and estrogen/ghrelin administration. Urethral sphincter signal intensity
      decreased without reaching sham levels after drug administration. Estrogen and/or
      ghrelin replacement reverses the ovariectomy-induced exacerbation of biochemical
      cellular ageing in the anal sphincter and levator muscle of middle-aged rats.

PMID- 16900440
TI  - Father-infant interaction patterns as precursors of children's later
      externalizing behavior problems: a longitudinal study over 11 years.
AB  - AIM: This study examined the extent to which fathers' and infants' interaction
      behavior were related to children's externalizing behavior problems at age 8 and
      11 years. METHODS: In a prospective longitudinal study of children at risk for
      later psychopathology, 72 fathers and their 3-month-old children were videotaped
      and evaluated during a standardized playing and nursing situation. Externalizing
      behavior problems at age 8 and 11 years were assessed using Achenbach's Child
      Behavior Checklist. RESULTS: In the high externalizing group, fathers were found
      to be less responsive and less sensitive (the latter only with respect to girls)
      during early interaction than fathers of the low externalizing group, while
      children were more positive with their fathers. Furthermore, low scores on the
      interaction pattern of "sensitive fathering/negative infant" and high scores on
      the "nonresponsive fathering or active infant" pattern were associated with more
      externalizing problems. CONCLUSION: These findings suggest that father and infant
      interaction behaviors during early infancy may predict later problem behaviors at
      school age, although the mechanisms underlying this relationship have yet to be
      identified.

PMID- 16900439
TI  - Risperidone augmentation of clozapine: a critical review.
AB  - OBJECTIVE: Atypical antipsychotics are frequently used as augmentation agents in
      clozapine-resistant schizophrenic patients. Risperidone (RIS) is the one most
      studied as a clozapine (CLZ) adjunct. The aim of this study is to critically
      review all published studies regarding the efficacy and safety of RIS as an
      adjunctive agent in CLZ-resistant schizophrenic or schizoaffective patients.
      METHODS: A MEDLINE search from January 1988 to June 2005 was conducted.
      Identified papers were examined against several clinical, pharmacological and
      methodological parameters. RESULTS: A total of 15 studies were found (2
      randomized controlled trials, 3 open-label trials (OTs) and 8 case-studies (CSs))
      comprising 86 schizophrenic or schizoaffective patients (mean age 38.4 years).
      Mean CLZ dosage during the combined treatment was 474.2 mg/day. Plasma CLZ levels
      were assessed in 62 patients (72.1%). RIS was added at a mean dosage of 4.6
      mg/day for a mean of 7.9 weeks. Significant improvement in psychopathology was
      reported for 37 patients (43%). A lower RIS dosage and a longer duration of the
      trial seemed to be associated with a better outcome. Main side effects reported
      were: extrapyramidal symptoms or akathisia (9.3%), sedation (7%) and
      hypersalivation (5.8%). CONCLUSIONS: Existing evidence encourages the use of RIS
      as an adjunctive agent in CLZ-resistant schizophrenic or schizoaffective
      patients.

PMID- 16900441
TI  - Cardioprotection mediated by rosiglitazone, a peroxisome proliferator-activated
      receptor gamma ligand, in relation to nitric oxide.
AB  - Activation of peroxisome proliferator-activated receptor (PPAR) gamma protects
      from myocardial ischemia/reperfusion injury. The aim of the study was to
      investigate whether the cardioprotective effect of PPARgamma is related to nitric
      oxide (NO). METHODS: Wild type (WT) and endothelial NO synthase (eNOS) knockout
      (KO) mice received 3 mg/kg of the PPARgamma agonist rosiglitazone or vehicle (n =
      6-9 in each group) i. p. 45 min before anesthesia. The hearts were isolated,
      perfused in a Langendorff mode and subjected to global ischemia and 30 min
      reperfusion. The hearts of another two groups of WT mice received the NOS
      inhibitor L-NNA (100 micromol/l) or vehicle in addition to pre-treatment with
      vehicle or rosiglitazone. RESULTS: In the WT heart, rosiglitazone increased the
      recovery of left ventricular function and coronary flow following ischemia in
      comparison with the vehicle group.L-NNA did not affect recovery per se but
      significantly blunted the improvement in the recovery of left ventricular
      function induced by rosiglitazone. In the KO group rosiglitazone suppressed the
      recovery of myocardial function following ischemia. Expression of eNOS was not
      affected, but phosphorylated eNOS was significantly increased by rosiglitazone in
      the WT hearts (P < 0.05). CONCLUSION: These results suggest that the
      cardioprotective effect of the PPARgamma agonist rosiglitazone is mediated via NO
      by phosphorylation of eNOS.

PMID- 16900442
TI  - Nicorandil opens mitochondrial K(ATP) channels not only directly but also through
      a NO-PKG-dependent pathway.
AB  - Nicorandil, a hybrid of nitrate generator and potassium channel opener, protects
      ischemic myocardium by opening mitochondrial ATP sensitive potassium (mitoK(ATP))
      channels. We recently found that nitric oxide (NO) opened K(ATP) channels in
      rabbit hearts by a protein kinase G (PKG) mechanism. This study examined whether
      the NO-donor property of nicorandil also contributes to opening of mitoK(ATP)
      channels through PKG. MitoK(ATP) channel opening was monitored in adult rabbit
      cardiomyocytes by measuring reactive oxygen species (ROS) production, an
      established marker of channel opening. Nicorandil increased ROS production in a
      dose-dependent manner. The selective mitoK(ATP) channel inhibitor 5
      hydroxydecanoate (200 microM) completely blocked ROS production by nicorandil at
      all doses. The PKG inhibitor 8-bromoguanosine-3',5'-cyclic monophosphorothioate,
      Rpisomer (Rp-8-Br-cGMPs, 50 microM) shifted the dose-ROS production curve to the
      right with an increase of the EC(50) from 2.4 x 10(-5) M to 6.9 x 10(-5) M. Rp- 8
      Br-cGMPs did not affect the increase in ROS production by the selective
      mitoK(ATP) channel opener diazoxide while it completely blocked increased ROS
      production from the NO donor S-nitroso-N-acetylpenicillamine (1 microM).
      Furthermore ODQ, an antagonist of soluble guanylyl cyclase, blocked nicorandil's
      ability to increase ROS generation. These results indicate that nicorandil, in
      addition to its direct effect on the channels, opens mitoK(ATP) channels
      indirectly via a NO-PKG signaling pathway.

PMID- 16900443
TI  - [Falls and their sequelae].

PMID- 16900444
TI  - [Characteristics of falls in physically active community-dwelling older people:
      findings from the "Standfest im Alter" study].
AB  - BACKGROUND: Falls are common in physically active older people due to their
      increased exposure to hazardous situations. However, most studies of the
      characteristics and circumstances of falls are based on frail older people.
      OBJECTIVE: To describe the location, time, cause, injuries and medical treatment
      associated with falls in a physically active group of older people. METHODS:
      Prospective falls data over a 12-month period were obtained from 293 people (163
      men and 130 women) aged between 70 and 90 years who took part in the "Standfest
      im Alter" study, a randomized controlled trial conducted in Erlagen, Germany.
      RESULTS: During the study period, there were 322 falls. 122 participants (42%)
      fell at least once and 62 (21%) fell on multiple occasions. The typical fall
      occurred outside the home during leisure activities, at midday or in the
      afternoon and did not result in injury or admission to hospital. There were no
      differences in the rate of falls according to gender; however, fall location,
      time of fall, fall injury and visits to the doctor after the fall were all
      influenced by gender. CONCLUSIONS: The results of this study provide useful
      insights into the characteristics and circumstances of falls in physically active
      older people living in the community, which may assist with the development of
      future falls prevention activities.

PMID- 16900445
TI  - [Screening of fall risk in frail, but still independently living senior
      citizens].
AB  - Mobility is one of the most important factors for well-being and autonomy in old
      age. Impairments in mobility, falls and fear of falling are, therefore, of
      prognostic value. Falls generally result from an interaction of multiple risk
      factors. However, older people are often not aware of the risks of falling. They
      neither recognize risk factors nor report these factors to their physicians. The
      aim of this study was to develop and to test a self-reported multidimensional
      screening instrument to evaluate risk factors of falling in community-dwelling
      older people. Therefore, we identified multiple risk factors of falls based on a
      systematic literature review and then developed a new questionnaire - the Senior
      Citizen Risk of Falling Check. Risk factors, i.e. cognitive disorders, that are
      closely associated with the demand of nursing care were not covered in this
      relatively healthy target group. We pretested this instrument and adapted it
      before its use in a pilot test in residents of a sheltered housing complex in
      Hamburg. A group of 117 residents (average age 82.9 years, range 68.2-98.2 years,
      83.8% women), all without care needs (assessed by the German health and care
      insurance system) returned the Senior Citizen Risk of Falling Check. Within 2
      weeks all 117 participants were interviewed by telephone to analyze the test
      retest reliability of the instrument (Cohen's kappa). We administered 13
      questions on visual and hearing deficits, neurological impairment, depressive
      mood, medication use, muscle weakness, gait and balance deficits, nutrition, and
      history of falls. On average, 6 risk factors were reported (range 0-12).
      Reductions in gait speed (64.1%) was most frequently mentioned. Of the
      participants, 30.8% fell at least once during the last year and 22.2% of these
      falls resulted in injuries (fractures, hematomas, laceration, pain). Cohen's
      kappa was good (2/13 questions) to excellent (10/13 questions) with one exception
      (balance question kappa=0.20). The study results confirm good test-retest
      reliability of the fall risk screening Senior Citizen Risk of Falling Check. At
      the moment we are working on the validation of this questionnaire to provide it
      to senior citizens throughout Hamburg in cooperation with the City of Hamburg.

PMID- 16900446
TI  - Accidental falls among community-dwelling older adults: improving the
      identification process of persons at risk by nursing staff.
AB  - Elderly persons living in the community are a heterogeneous population. Among
      them, the screening of persons at risk of falling is still a matter of debate.
      The aim of this analysis was to improve the identification process of elderly
      persons living in the community at risk for falling by nursing staff of community
      based services. A secondary analysis was performed with the data from a
      prospective non-randomized interventional trial. The study included 268 community
      dwelling older adults (mean age of 82 years, 81.3% female) from Ulm and Neu-Ulm
      with a followup period of 12 months. Fall risk indicators were extracted from the
      nursing assessment and analysis with crude odds ratios revealed the following
      risk indicators for falls: assistance when transferring, bathing and climbing a
      flight of stairs as well as fall history. Afterwards, fall risk indicators were
      selected by backward elimination in a multiple logistic regression. Variable
      selection identified a positive fall history and the need for assistance when
      bathing as important risk indicators. These two risk indicators could be used as
      a screening tool, which would be easy to perform by nursing staff in their daily
      work. This screening test defined as more than one fall in the last 12 months or
      bathing assistance, the first ADL to be affected in the disablement process, has
      a sensitivity of 85.3% and a specificity of 42.1%.

PMID- 16900447
TI  - [Age-related differences in functional tests to assess the risk of falling in
      patients with knee pain].
AB  - In the present cross-sectional study the results of three tests to assess the
      risk of falling were examined for a correlation with advancing age of the
      participants. Each of the 188 community dwelling active participants aged 40
      years or older with a history of knee pain performed the Timed Up and Go (TUG),
      the Performance Oriented Mobility Assessment (POMA, "Tinetti Test") and a less
      established simple test of dynamic balance, the Four Square Step Test (FSST). Age
      related differences in performance in the Timed Up and Go and the Performance
      Oriented Mobility Assessment have been shown in previous studies and are also
      present in this sample. For the Four Square Step Test an association of test
      performance and age has been shown for the first time in this study. Further
      investigation is required to determine the quality of these three tests regarding
      their ability to assess the risk of falling in patients with knee pain.

PMID- 16900448
TI  - The Tinetti test: Babylon in geriatric assessment.
AB  - The Tinetti test has been recommended and widely used in the elderly to assess
      mobility, balance and gait, and predict falls. Different versions can be found. A
      systematic literature search identified 37 publications on the Tinetti test and
      falls. Wide variations were found concerning name of the instrument, test items,
      scoring, and cut-off values. This heterogeneity interferes with evaluations of
      the test's validity, reliability and generalisability. Researcher and clinicians
      should be aware of this fact, when dealing with the Tinetti test.

PMID- 16900449
TI  - A follow-up study on fall and fracture incidence in long-term care including the
      role of formal caregiver time on fall incidence rates.
AB  - OBJECTIVE: To examine the impact of a fall prevention programme over a 12 month
      follow-up period after the introduction of a RCT and to describe possible
      differences between incidence density rate of falls associated with caregiver
      time during weekends and ordinary working days. DESIGN: Prospective observational
      study, duration 12 months. SETTING: Six community nursing homes, Germany.
      PARTICIPANTS: Long-stay residents (n=881); 771 resident years; median age 85.0
      years (min 60; max 101); 79.1% female. MEASUREMENTS: Incidence density rate of
      falls and fractures, staff time per resident. RESULTS: The incidence density rate
      over all days was 1367/1000 resident years (RY) for falls [95% confidence
      interval 1041;1693]. The incidence density rate of hip fractures was 29/1000 RY
      [95% confidence interval 12;45] and 29/1000 RY [95% confidence interval 12;45]
      for non-hip fractures. The incidence density rate showed similar results
      comparing weekends/ public holidays vs normal working days; falls 1193 vs 1447/
      1000 RY; hip fractures 25 vs 30/ 1000 RY and other fractures 16 vs 34/1000 RY.
      CONCLUSION: During the period, we observed a marked decline of the fracture rate
      compared with the controlled phase of the intervention trial. A lower number of
      nursing care hours on weekends was not associated with a higher incidence density
      rate for falls, fallers, or any type of fracture.

PMID- 16900450
TI  - [The German version of the Falls Efficacy Scale-International Version (FES-I)].
AB  - The German version of the Falls Efficacy Scale-International Version (FES-I),
      which is presented, was developed for the documentation of fall-related
      selfefficacy in older persons by a EU-funded expert network (Prevention of Falls
      Network Europe ProFaNE). The FES-I represents a modification of the original
      Falls Efficacy Scale (FES), including additional items on complex functional
      performances and social aspects of falls. The FES-I shows high internal
      reliability (Cronbach's alpha = 0.96) as well as high test-retest reliability
      (r=0.96). The mean inter-item correlation was: r = 0.55 (Range r = 0.29-0.79).
      Results of validation studies for the FES-I in community dwelling older persons
      for different European countries and geriatric patients with cognitive impairment
      will be published in the near future.

PMID- 16900451
TI  - [Effective, indicated--and yet without benefit? The goals of dementia drug
      treatment and the well-being of the patient].
AB  - Individual treatment decisions for patients with Alzheimer dementia are often
      characterized by uncertainty about the actual benefit that specific treatments or
      procedures may bring about. It often even remains unclear how the benefit of a
      treatment may be determined. In this paper, three criteria for determining the
      benefit of a treatment measure are developed: An intervention (1) must be
      effective and (2) able to achieve a clinically relevant goal, which is (3)
      desirable for the individual patient. By using example of anti-dementia drug
      treatment, it will by shown that even if standard goals of dementia care are
      achieved, the benefit for the patient may still be questionable. A cognitive
      improvement or a delay of cognitive decay may even harm the patient. Therefore it
      is not sufficient to focus on the efficacy of a drug and on general goals of care
      when making decisions about individual dementia treatments. Rather it is
      necessary to reflect and discuss explicitly the goals of the individual patient.
      As shown by various examples, this will facilitate coherent, patient-orientated
      treatment decisions.

PMID- 16900452
TI  - [Behind each door you will find death: institutionalized dying].
AB  - Basic changes in our society and social system lead to a repression of old, frail
      and impaired people. They are increasingly institutionalized, and the issue of
      death and dying is delegated to experts. The present investigation describes the
      burden of routine care of dying people. "Mixed methodology" was used to obtain
      comprehensive and relevant data. General questions were deduced for the research
      subject based on qualitative interviews with 17 members of the nursing staff.
      These questions complete the questionnaire used to conduct the survey in 49
      nursing homes. All kinds of occupational groups took part in the study. The
      quantitative data (n=894) were analyzed descriptively and proved for group
      differences with nonparametric methods. The results show that talking about the
      end of life with residents is difficult for almost a quarter of the participating
      persons. Nearly one third of the staff members tend to avoid the topic of death
      and dying when talking with relatives. High importance was attached to further
      interdisciplinary training in terminal care. Working together with different
      occupational groups like hospice volunteers, chaplains, psychologists and
      caregivers is seen as a fruitful way and a possibility of increasing the quality
      of dying in nursing homes.

PMID- 16900456
TI  - Model selection and mixed-effects modeling of HIV infection dynamics.
AB  - We present an introduction to a model selection methodology and an application to
      mathematical models of in vivo HIV infection dynamics. We consider six previously
      published deterministic models and compare them with respect to their ability to
      represent HIV-infected patients undergoing reverse transcriptase mono-therapy. In
      the creation of the statistical model, a hierarchical mixed-effects modeling
      approach is employed to characterize the inter- and intra-individual variability
      in the patient population. We estimate the population parameters in a maximum
      likelihood function formulation, which is then used to calculate information
      theory based model selection criteria, providing a ranking of the abilities of
      the various models to represent patient data. The parameter fits generated by
      these models, furthermore, provide statistical support for the higher viral
      clearance rate c in Louie et al. [AIDS 17:1151-1156, 2003]. Among the candidate
      models, our results suggest which mathematical structures, e.g., linear versus
      nonlinear, best describe the data we are modeling and illustrate a framework for
      others to consider when modeling infectious diseases.

PMID- 16900457
TI  - Novel biomaterials in the management of anal fistulas.

PMID- 16900462
TI  - Interrelationship of childhood trauma, neuroticism, and depressive phenotype.
AB  - Both childhood trauma (CT) and genetic factors contribute to the pathophysiology
      of depression. We studied the relationship of CT to age of onset (AO) of
      depression, personality traits, and expression of symptom dimensions in 324
      adults with recurrent unipolar depression. Subjects received structured
      psychiatric interviews and completed CT, depressive symptom, and personality
      rating questionnaires. Experience of at least one type of trauma was reported by
      79.9% of subjects, and the most common forms of trauma were physical neglect,
      emotional abuse, and emotional neglect. There was an earlier AO of depression in
      the groups that reported CT compared to those that reported none, with earliest
      AO occurring in those who had experienced the highest levels of CT. There were no
      significant correlations between overall CT scores and neuroticism or
      extraversion. Total CT was a significant (P=.008) predictor of the Mood symptom
      dimension, mostly accounted for by emotional abuse (P=.019), and physical neglect
      predicted the Anxiety symptom dimension (P=.002). All types of CT are commonly
      reported in individuals with depression, and emotional abuse and physical
      neglect, though previously less well identified, appear to have an important role
      in the pathogenesis of depressive disorders. The effect of CT on individuals with
      an underlying genetic vulnerability to depression may result in differences in
      depressive phenotype characterized by earlier AO of depression and the expression
      of specific depressive symptom dimensions.

PMID- 16900463
TI  - Cytologic diagnosis of pancreatic endocrine tumors by endoscopic ultrasound
      guided fine-needle aspiration: a review.
AB  - Precise localization and diagnosis of pancreatic endocrine tumors (PETs) is
      important, because pancreatic PETs have different clinical and biological
      behavior and treatment modalities than do exocrine pancreatic tumors. In contrast
      to the much more common exocrine adenocarcinomas, cytologic studies of PET are
      relatively rare and many cytopathologists lack experience with the
      cytomorphologic features of these tumors.During the last 10 yr, endoscopic
      ultrasound (EUS)-guided fine-needle aspiration (FNA) has matured into an
      accurate, highly sensitive, and cost-effective modality for the preoperative
      localization of pancreatic PETs. This has resulted in an increased number of PETs
      first sampled as cytology specimens. This manuscript focuses on the
      cytomorphologic features most suggestive of pancreatic PETs, differential
      diagnosis, and diagnostic pitfalls of PETs. The technical development of EUS
      guided FNA and the ancillary studies for pancreatic PETs are also reviewed. The
      data summarized in this review indicate that EUS-FNA is a valuable method in the
      recognition of pancreatic PETs and in most cases cytopathologists could reach a
      correct diagnosis of these tumors, including their hormone producing capability
      on aspirated cytologic material.

PMID- 16900464
TI  - Changes in perfectionism following cognitive-behavioral treatment for social
      phobia.
AB  - Previous studies have found that social phobia (social anxiety disorder) is
      associated with elevated levels of perfectionism, particularly concerns over
      making mistakes (CM) and doubts about actions (DA). This study investigated the
      extent to which various dimensions of perfectionism change as a result of
      participating in a 12-session cognitive-behavioral group treatment for social
      phobia. One hundred seven individuals completed the Frost Multidimensional
      Perfectionism Scale before and after treatment. Participants improved on several
      measures of social anxiety, generalized anxiety, and depression. With respect to
      perfectionism, significant reductions were seen on total perfectionism scores and
      scores on particular dimensions (CM, DA, organization), but not on other
      dimensions (personal standards, parental expectations, parental criticism).
      Furthermore, changes in DA and to some extent CM predicted posttreatment levels
      of social anxiety after controlling for pretreatment levels of social anxiety and
      changes in anxiety and depression. Implications of these findings are discussed.

PMID- 16900465
TI  - Depressive, anxiety, and somatoform disorders in primary care: prevalence and
      recognition.
AB  - Recent studies emphasize the negative impact of comorbidity on the course of
      depression. If undiagnosed, depression and comorbidity contribute to high medical
      utilization. We aimed to assess (1) prevalences of depression alone and with
      comorbidity (anxiety/somatoform disorders) in primary care, (2) coexistence of
      anxiety/somatoform disorders in depressive patients, and (3) diagnostic validity
      of two screeners regarding depression with versus without comorbidity. We
      examined 394 primary care outpatients using the Composite International
      Diagnostic Interview (CIDI), the General Health Questionnaire (GHQ-12), and the
      Well-Being Index (WHO-5). We conducted configurational frequency analyses to
      identify nonrandom configurations of the disorders and receiver operating
      characteristic (ROC)-analyses to assess diagnostic validity of the screeners.
      Point prevalence of any depressive disorder was 22.8%; with at least one comorbid
      disorder, 15%; and with two comorbid conditions, 6.1%, which significantly
      exceeded expected percentage (0.9%, P< or =.0001). Depression without comorbidity
      occurred significantly less often than expected by chance (P< or =.0007).
      Comorbidity of depressive and anxiety or somatoform disorders was associated with
      a high odds ratio (6.25). The screeners were comparable regarding their
      diagnostic validity for depression with [GHQ-12: area under the curve (AUC)=0.86;
      WHO-5: AUC=0.88] and without comorbidity (GHQ-12: AUC=0.84; WHO-5: AUC=0.86). It
      can be concluded that comorbidity between depression and anxiety/somatoform
      disorders in primary care may occur much more frequently than expected. These
      results confirm assumptions that the current division between depression and
      anxiety might be debatable. Validity of screeners tested in our study was not
      affected by comorbid conditions (e.g., anxiety or somatoform disorders).

PMID- 16900466
TI  - Protein splicing in cis and in trans.
AB  - Intein-mediated protein splicing is a self-catalytic process in which the
      intervening intein sequence is removed from a precursor protein and the flanking
      extein segments are ligated with a native peptide bond. Splice junction proximal
      residues and internal residues within the intein direct these reactions. The
      identity of these residues varies in each intein, as groups of related residues
      populate conserved motifs. Although the basics of the four-step protein splicing
      pathway are known, mechanistic details are still unknown. Structural and kinetic
      analyses are beginning to shed some light. Several structures were reported for
      precursor proteins with mutations in catalytic residues, which stabilize the
      precursors for crystallographic study. Progress is being made despite limitations
      inherent in using mutated precursors. However, no uniform mechanism has emerged.
      Kinetic parameters were determined using conditional trans-splicing (splicing of
      split precursor fragments after intein reassembly). Several groups concluded that
      the rate of the initial acyl rearrangement step is rapid and Asn cyclization
      (step 3) is slow, suggesting that this latter step is rate limiting.
      Understanding the protein splicing pathway has allowed scientists to harness
      inteins for numerous applications.

PMID- 16900467
TI  - Structure and function of cis-prenyl chain elongating enzymes.
AB  - All carbon skeletons of isoprenoids, whose chain lengths vary widely from geranyl
      diphosphate (C10) to natural rubber (C>10,000), are synthesized by sequential
      condensation of isopentenyl diphosphate with an allylic diphosphate through
      catalytic functions of a group of enzymes commonly called "prenyltransferases."
      Prenyltransferases are classified into two major groups, trans- or (E)
      prenyltransferases and cis- or (Z)-prenyltransferases, according to the geometry
      of the prenyl chain units in the products. From the year 1987, many genes
      encoding trans-prenyltransferases were cloned and clearly characterized. In
      contrast, the structure and detailed mechanism of cis-prenyltransferase was
      completely unknown until the identification of a gene encoding the undecaprenyl
      diphosphate (UPP) synthase from Micrococcus luteus B-P 26 in 1998. Not only the
      primary but also the tertiary structure of the UPP synthase is quite different
      from that of the trans-prenyltransferases. Multiple alignment of the primary
      structures of cis-prenyltransferases identified from various organisms reveals
      five highly conserved regions. Site-directed mutagenesis of the conserved amino
      acid residues in UPP synthases based on the crystal structure has elucidated the
      basic catalytic mechanisms. Moreover, comparison of the structures of short-,
      medium-, and long-chain cis-prenyltransferases reveals important amino acid
      residues for product chain length determination, which enabled us to understand
      the regulation mechanism of the ultimate chain length among cis
      prenyltransferases.

PMID- 16900468
TI  - Lung cell fiber evanescent wave spectroscopic biosensing of inhalation health
      hazards.
AB  - Health risks associated with the inhalation of biological materials have been a
      topic of great concern; however, there are no rapid and automatable methods
      available to evaluate the potential health impact of inhaled materials. Here we
      describe a novel approach to evaluate the potential toxic effects of materials
      evaluated through cell-based spectroscopic analysis. Anchorage-dependent cells
      are grown on the surface of optical fibers transparent to infrared light. The
      probe system is composed of a single chalcogenide fiber (composed of Te, As, and
      Se) acting as both the sensor and transmission line for infrared optical signals.
      The cells are exposed to potential toxins and alterations of cellular composition
      are monitored through their impact on cellular spectral features. The signal is
      collected via evanescent wave absorption along the tapered sensing zone of the
      fiber through spectral changes between 3,000 and 600 cm(-1) (3,333-16,666 nm).
      Cell physiology, composition, and function are non-invasively tracked through
      monitoring infrared light absorption by the cell layer. This approach is
      demonstrated with an immortalized lung cell culture (A549, human lung carcinoma
      epithelia) in response to a variety of inhalation hazards including gliotoxin (a
      fungal metabolite), etoposide (a genotoxin), and methyl methansesulfonate (MMS,
      an alkylating agent). Gliotoxin impacts cell metabolism, etoposide impacts
      nucleic acids and the cell cycle, and MMS impacts nucleic acids and induces an
      immune response. This spectroscopic method is sensitive, non-invasive, and
      provides information on a wide range of cellular damage and response mechanisms
      and could prove useful for cell response screening of pharmaceuticals or for
      toxicological evaluations.

PMID- 16900469
TI  - Endometrial glandular and stromal breakdown, part 1: cytomorphological
      appearance.
AB  - Endometrial carcinoma is the most common invasive neoplasm of the female
      reproductive tract. Early detection and accurate diagnosis of these lesions and
      its precursor by endometrial cytology is now accepted in Japan and regarded as an
      effective primary method of evaluating endometrial pathology (atypical
      hyperplasia or carcinoma). Careful cytomorphologic evaluation of the abnormal
      endometrial lesions has made possible an accurate and reproducible microscopic
      assessment. The current study was conducted to determine the significance of
      endometrial cytology on disordered endometrium associated with anovulation when
      compared with endometrial hyperplasia. From January 1998 through April 2004, 144
      cases on which histopathological diagnoses were obtained by endometrial curettage
      after taken direct endometrial sample by Endocyte. The materials comprise 49
      cases of normal proliferative endometrium, and 63 cases of endometrial
      hyperplasia without atypia were prepared as control cases. The cytomorphology was
      examined involving so-called endometrial glandular and stromal breakdown (EGBD).
      EGBD cases evidenced significant numbers of stromal cells condensed and formed
      compact nests with hyperchromatic nuclei and little or no cytoplasm. They were
      often associated with fragmented clusters of endometrial glands with condensed
      cluster of stromal cells. Both the fragmented cluster of endometrial glands and
      condensed cluster of stromal cells are a characteristic cytologic feature of EGBD
      endometrium on the cyto-architectural diagnosis. The combination of these
      cellular patterns is highly specific to this abnormal pathological condition in
      EGBD endometrium. To improve the accuracy of the cytodiagnosis, it is important
      that the cytology of the EGBD endometrium should be diagnosed negative; as a
      result, we can achieve successful endometrial cytology with cyto-architectural
      criteria for the endometrial pathology.

PMID- 16900470
TI  - Cytological identification of metastatic epithelial nephroblastoma in pleural
      fluid: report of a case and review of literature.
AB  - Nephroblastoma (Wilms' tumor) is the most common childhood renal tumor and
      usually presents with a histology and cytology consisting of blastemal,
      epithelial, and stromal cells. Effusions are not uncommon and may suggest an
      unfavorable prognosis when containing anaplastic tumor cells. In the present
      case, we report the cytological appearance of a Wilms' tumor metastatic to the
      pleura. The effusion consisted primarily of tumor cells demonstrating epithelial
      differentiation. The tumor cells mostly presented as three-dimensional aggregates
      in an inflammatory background. Many cystic and tubular structures were
      identified. The tumor cells demonstrated strong CD56 and WT1 immunoreactivity.
      The histology of a subsequent surgical specimen reflected the features seen in
      cytology.

PMID- 16900471
TI  - Dutch solutions for liquid-based cytology: analysis of unsatisfactory slides and
      HPV testing of equivocal cytology.
AB  - The liquid-based techniques to obtain microscopy slides for cervical screening
      have replaced conventional smears almost completely in the USA, but not in all
      European countries. The decision making process to use liquid-based cytology
      (LBC) for nationwide screening programs depends on the health system. In a pilot
      study of over 7,000 screenees, we analyzed the unsatisfactory LBC slides and
      tested the equivocal cytologies for HPV by using the LiPA test. For comparison
      over 48,000 conventional screening data were used. Compared to conventional
      smears, the LBC slides were highly cellular, the state of fixation was much
      better, and obscuring blood did not exist. The unsatisfactory rate showed an
      increase from 262/100,000 (conventional smears) to 357/100,000 (LBC slides) due
      to too thick, undiagnosable epithelial fragments on the LBC slides. HPV testing
      of the equivocal cytology leads to a better patient management and less
      unnecessary referrals.

PMID- 16900472
TI  - Cytologic aspect of mucinous tubular and spindle-cell renal carcinoma in fine
      needle aspirates.

PMID- 16900473
TI  - Fine-needle aspiration of a chordoma and its recurrence 19 years after.

PMID- 16900474
TI  - Fine-needle aspiration of soft tissue leiomyosarcoma: an analysis of the most
      common cytologic findings and the value of ancillary techniques.
AB  - This study aims to determine the diagnostic accuracy of fine-needle aspiration
      cytology (FNAC) of primary leiomyosarcoma (LMS) of soft tissue and to review
      diagnostic criteria and adjunctive methods, which can contribute to a confident
      diagnosis. We evaluated the preoperative FNAC in 89 patients with primary LMS for
      the following: cytomorphology and correspondence of FNA to histological features
      of excised tumors and clinical data. In addition, the utility of adjunctive
      techniques was analyzed and other spindle-cell lesions in the differential
      diagnoses were discussed. An unequivocal, malignant diagnosis was rendered by
      FNAC in 78 cases; 74 tumors were diagnosed as sarcoma, of which 31 as LMS or
      suspicion of LMS. In addition, three smears were labeled as malignant tumor, one
      as carcinoma metastasis, and three as neurilemmoma. Seven aspirates were
      inconclusive and one insufficient. On reevaluation, the diagnostic smears in most
      cases contained tumor cell fascicles with an admixture of dispersed cells or
      stripped nuclei. The most common cells were spindle cells with elongated, blunt
      ended, segmented or fusiform nuclei, and round/polygonal cells, often with
      rounded or indented nuclei. In addition, 51 cases showed pleomorphic, often
      multinucleated cells. Osteoclasts, intranuclear vacuoles, and mitoses occurred in
      14, 47, and 27 cases, respectively. Thus, most high-grade LMSs have cytologic
      features that allow diagnosis of sarcoma. Ancillary studies can confirm the
      diagnosis of LMS and help in the correct interpretation of predominant spindle
      cell or epitheloid-cell smears resembling neurilemoma or carcinoma, respectively.

PMID- 16900475
TI  - Accuracy of diagnosis of atypical glandular cells - Conventional and ThinPrep.
AB  - The incidence of glandular cervical malignancy is steadily increasing. Glandular
      abnormalities are more frequently diagnosed on cervical smears. In this study, we
      attempt to evaluate our experience with glandular cytology and to assess the
      sensitivity and specificity of the ThinPrep (TP) over conventional Papanicolaou
      (Pap) smears. Glandular abnormalities during a 3-yr period from October 2000 to
      October 2003 were retrieved from our cytology database. The study group comprised
      smears from 369 patients, 272 conventional Pap smears (CPSs) and 97 TP from a
      total of 400,184 smears. The types of glandular abnormalities were tabulated
      following a modified Bethesda classification. Correlation with histology and
      follow-up cytology was achieved in all but six patients. Significant lesions were
      identified in 116/272 (PPV 42.6%) of CPSs and 58/97 (PPV 58.9%) TPs. Pure
      glandular abnormalities numbered 125 conventional and 51 TP; significant lesions
      identified in this group were 36/125 (PPV 28.8%) CPS and 26/51 (PPV 50.9%) TP.
      Statistical analysis showed significant differences for positive predictive
      values of TP and CPS and a suggestion of increased sensitivity. The main limiting
      factor was small numbers of glandular abnormalities and a desirable longer study
      time.

PMID- 16900476
TI  - Ganglioneuroma presenting as periesophageal mass.

PMID- 16900477
TI  - A case of mucinous spherulosis of the breast diagnosed retrospectively in FNA
      material.
AB  - We describe for the first time the cytologic features of mucinous spherulosis
      (MS), a variant of collagenous spherulosis (CS) of the breast characterized by
      cribiform structures containing lightly basophilic material, embedded in a
      loosely mucinous acellular background. Histologically, the lesion was part of a
      complex hyperplasia containing foci of sclerosing adenosis, and foci of atypical
      ductal hyperplasia (ADH). Immunohistochemical study showed reactivity with smooth
      muscle actin and focally for cytokeratin 14. Cytologic features of MS were
      recognized retrospectively and consisted of intermediate to large round hyaline
      spherules, naked or surrounded by myoepithelial cells. A fibrillary radial
      appearance was observed with Diff-Quick stain. We draw attention to the
      importance of recognizing these features because they can easily pose problems
      either by being overlooked or overdiagnosed as mucinous carcinoma. Differential
      diagnosis is briefly discussed.

PMID- 16900478
TI  - Kuttner's tumor of the submandibular glands: report of five cases with fine
      needle aspiration cytology.
AB  - Kuttner's tumor (KT) is a benign tumor-like lesion of the salivary gland that
      mimics neoplasm clinically because of presentation as a hard mass. Recently, the
      histomorphological and immunohistochemical findings of this lesion have been
      analyzed, and differential diagnostic problems relating to salivary gland
      lymphoma have been discussed. However, currently there is little information on
      the cytological findings of those lesions. We present cytological findings from
      five such cases using fine-needle aspiration cytology (FNAC). FNAC of this lesion
      may present a diagnostic challenge to the cytologist as lesions share some
      cytologic features with inflammatory process containing numerous lymphoid cells.
      Smears obtained from two cases contained moderate to large numbers of lymphoid
      cells without definite cytological atypia, scattered ductal structures, and
      acinar cell clusters. The remaining three cases showed low cellularity probably
      attributable to fibrosis that made it difficult to aspirate the cellular element.
      FNAC findings of scattered ductal structures surrounded by collagens and
      infiltrated by a mixed population of lymphoid cells, not specific for KT, are
      highly suggestive of the diagnosis with the appropriate clinical findings.
      However, a portion of cytological specimens of KT containing relatively large
      numbers of lymphoid cells should be differentiated from malignant lymphoma
      arising from the submandibular gland.

PMID- 16900479
TI  - Worm-like artifacts in exfoliative cytology.
AB  - The presence of worms in cytological smears is occasionally reported, although
      various other structures exist that may be confused with such parasites. We
      present eight worm-like artifacts observed in routine Papanicolaou smears.
      Recognition of these structures is important to avoid overvaluation or confusion
      with true worms.

PMID- 16900480
TI  - Routine vaginal Pap test is not useful in women status-post hysterectomy for
      benign disease.
AB  - The US Preventive Services Task Force (USPTF) has recommended that routine
      vaginal Pap (V-Pap) screening is unnecessary for women status-post (S/P) total
      hysterectomy (T-Hyst) for benign disease (Guide to Clinical Preventive Services.
      2nd ed. Baltimore, MD: Williams & Wilkins; 1996. p 105-118). However, many US
      women continue to have V-Pap despite no risk for cervical cancer and minimal risk
      for primary vaginal cancer (JAMA 2004;291:2990). Herein, we report our experience
      with such patients. Computerized data of patients S/P T-Hyst for benign
      conditions over a 6-yr-period were retrospectively evaluated. Pap diagnoses of
      epithelial abnormalities (Ep Abnl), negative for intraepithelial lesion or
      malignancy with/without nonneoplastic findings (NILM-NN and NILM), were reviewed
      based on three age groups: group A, 18-44 yr; group B, 45-64 yr; and group C, >
      or =65 yr (JAMA 2004;291:2990). A control group was used.Of 1,860 T-Hyst 1,303
      (70%) were for benign disease. Of these 581/1303 (44.5%) patients had 819 current
      V-Paps (range, 1-5; mean, 1.4). The 581 patients were group A, 288 (49.5%); group
      B, 272 (46.8%); and group C, 21 (3.6%). Overall, the 819 V-Paps showed Ep Abnl,
      28 (3.4%); NILM-NN, 252 (30.7%); and NILM, 539 (65.8%). Of the 28 Ep Abnl, 19
      (67.8%) were atypical squamous cells of undetermined significance (ASCUS), and 9
      (32%) were low-grade vaginal intraepithelial lesions (LG-VAIN). The NILM-NN
      findings included organisms, atrophy, and endometriosis. On the basis of
      individual age groups, Ep Abnl were only seen in V-Paps of 7/288 (2%) of group A
      and 21/272 (8%) of group B patients. In 23 control patients, 7/71 (9.8%) current
      V-Paps showed Ep Abnl (ASCUS, 4 (57%); LG-VAIN, 3 (43%)). Continued V-Pap in
      women S/P T-Hyst for benign disease does not appear to be useful, particularly in
      those aged > or =65 yr.

PMID- 16900481
TI  - K-Ras and microsatellite marker analysis of fine-needle aspirates from
      intraductal papillary mucinous neoplasms of the pancreas.
AB  - Preoperative diagnosis of pancreatic cystic lesions is difficult despite the
      combination of cytomorphology, radiographic imaging characteristics, and fluid
      tumor markers such as carcinoembryonic antigen. Intraductal papillary mucinous
      neoplasms (IPMNs) represent a subset of preinvasive pancreatic cystic neoplasms
      and are associated with accumulated genetic mutations, especially K-ras and tumor
      suppressor genes such as p53. Application of molecular techniques to cyst fluid
      obtained by endoscopic ultrasound guided fine-needle aspiration (EUSFNA) may
      contribute to preoperative assessment. Sixteen patients with pancreatic cystic
      lesions had cyst fluid obtained by preoperative pancreatic EUSFNA or
      intraoperative aspiration. All patients subsequently underwent surgical resection
      of the pancreas and IPMN was documented in all (6 adenomas, 6 borderline tumors,
      and 4 carcinomas). DNA was extracted from the cyst fluids and mutational analysis
      for K-ras point mutations and loss of heterozygosity (LOH) analysis using a
      preselected panel of genomic loci were performed. LOH was observed in 3 of 4
      carcinomas as compared to 4 of 11 adenomas and borderline lesions (1 was QNS).
      LOH and K-ras mutations were both acquired in 2 of 4 carcinomas and in 1 of 12
      adenoma/borderline lesions. Although the study is small, molecular analysis for
      LOH and K-ras mutations is useful in the preoperative evaluation of cystic
      pancreatic lesions. Increasing degree of neoplasia appears to correlate with
      increased genetic abnormality using a panel of selected genomic markers.

PMID- 16900482
TI  - Inorganic functional materials: optimization of properties by structural and
      compositional control.
AB  - A review is given of the strategies used to dope inorganic solids and the
      consequences for properties such as ionic and electronic conductivity. Doping
      mechanisms involve either substitution of foreign ions onto lattice sites,
      creation of vacancies on either cation or anion sites, or population of normally
      empty interstitial sites by either anions or cations. Mechanisms for charge
      compensation associated with aliovalent doping are reviewed and examples are
      given in the fields of solid state ionics and high-temperature superconductivity.
      The strategies used for targeting materials with new properties are reviewed,
      including a surprising number of cases where startling new properties are
      encountered in well-known materials. Specific examples discussed include MgB2
      superconductor, Na beta-alumina sodium ion conductor, Ca12Al14O33 oxide ion
      conductor, LiCoMnO4 lithium battery cathode, doped Li4SiO4 tunable lithium ion
      conductor, and La-doped BaTiO3 ferroelectric, which can be either semiconducting
      or insulating. Examples are also given of a curious observation that
      extraordinary properties are often encountered in materials that are on the edge
      of stability, either structurally or compositionally or at the crossover between
      different property types.

PMID- 16900483
TI  - A phase 2 trial of all-trans-retinoic acid in combination with interferon-alpha2a
      in children with recurrent neuroblastoma or Wilms tumor: A Pediatric Oncology
      Branch, NCI and Children's Oncology Group Study.
AB  - BACKGROUND: The combination of the antiproliferative and differentiation-inducing
      effects of retinoids together with the antiproliferative, immunostimulatory, and
      differentiation-potentiating effects of interferon-alpha (IFN-alpha) were the
      basis for the development of this combination in pediatric patients with
      refractory neuroblastoma or Wilms tumor. PROCEDURE: A phase 2 trial of all-trans
      retinoic acid (ATRA), administered orally at a dose of 90 mg/m(2)/day in three
      divided doses for 3 consecutive days per week, and IFN-alpha2a, administered
      subcutaneously daily at a dose of 3 x 10(6) U/m(2)/day for 5 consecutive days per
      week, in 4 week cycles was performed. A two-stage design was used for each
      disease stratum. RESULTS: Seventeen patients (16 evaluable) with neuroblastoma,
      median age 9 years, and 15 patients (14 evaluable) with Wilms tumor, median age 6
      years, were enrolled. Overall, the combination was well tolerated, with headache
      being the most common toxicity observed. There were no complete or partial
      responses. The median number of cycles administered was 1 (range 1-9). Four
      patients with neuroblastoma had stable disease for 12 or more weeks. CONCLUSIONS:
      The combination of ATRA and IFN-alpha2a was inactive in children with relapsed or
      refractory neuroblastoma and Wilms tumor. The lack of activity with this
      combination in children with refractory neuroblastoma is similar to the
      disappointing phase 2 results of single agent 13-cis-retinoic-acid (13cRA) and
      does not support further development of ATRA for children with relapsed
      neuroblastoma.

PMID- 16900484
TI  - Rituximab for treatment of opsoclonus-myoclonus syndrome in neuroblastoma.
AB  - Opsoclonus-myoclonus syndrome (OMS) is a rare paraneoplastic syndrome that occurs
      in 2%-3% of patients with neuroblastoma. The cause of this syndrome is believed
      to be immune mediated, but the exact mechanism still remains unclear. There is an
      urgent need to improve our current strategies for treating patients with OMS, as
      many patients have significant long-term neurologic deficits and behavior
      disorders with current treatment approaches. Therapies that have shown to improve
      symptoms in these patients have ranged from ACTH and corticosteroids, to
      intravenous gammaglobulin and plasmapheresis. We report our experience with
      Rituximab in a patient with neuroblastoma and OMS.

PMID- 16900485
TI  - Complementary/alternative medicine use in a pediatric oncology unit in Turkey.
AB  - BACKGROUND: Important in the cancer therapy is the increasingly use of
      complementary/alternative medicine (CAM). The current study aims to establish the
      extent of use, the types of therapies employed, factors influencing, the reasons
      for choosing and the cost of CAM used in pediatric cancer patients in our clinic
      in Ankara, Turkey. PROCEDURE: A detailed questionnaire regarding demographic data
      and information about the use of CAM was completed by 95 patients who have
      attended the clinic between 1999 and 2000. RESULTS: Forty-nine patients (51.6%)
      had used one or more than one type of CAM. The most frequent (71.4%) was herbal
      medicine and biologic intake (stinging nettle, plant essence, honey of Anzer).
      The second one was religious therapy (40.8%). No correlation could be found
      between the use of CAM and parents education status, the level of income, number
      of siblings, the prognosis of the disease, the rate of satisfaction with the
      level of information given by the doctor at the time of diagnosis or the belief
      in the information given by the doctor about the prognosis (P > 0.05). All
      patients used CAM in addition to conventional therapy. CONCLUSIONS: More than
      half of the patients used CAM, with stinging nettle being the most common agent.
      Our patients place a high level of trust in their physicians and the conventional
      therapies offered by them; however, they also believe that the complementary
      therapies are harmless and, therefore, worth trying.

PMID- 16900486
TI  - Total syntheses of polyketide-derived bioactive natural products.
AB  - Recent progress of total syntheses in our laboratory has been described along
      with our background and methodologies. The target bioactive polyketides are
      classified into three categories according to their structures: (i) lactone-fused
      polycyclic compounds [(+)-cochleamycin A, (+)-tubelactomicin A, and (-)
      tetrodecamycin], (ii) aromatic compounds [(-)-tetracycline, (-)-BE-54238B,
      lymphostin, and (-)-lagunamycin], and (iii) acyclic polyketides [xanthocillin X
      dimethylether, (+)-trichostatin D, and (+)-actinopyrone A]. Features of the total
      syntheses are described. Original methodologies have been developed and applied
      to construct the inherent structures of the target molecules. Most syntheses
      cited herein are the first total syntheses, and the absolute structures of the
      target molecules have been determined.

PMID- 16900487
TI  - Etanercept for therapy-resistant macrophage activation syndrome.
AB  - Macrophage activation syndrome (MAS) is a severe, potentially fatal complication
      of childhood rheumatic diseases, especially systemic onset juvenile idiopathic
      arthritis (SoJIA). We report a 4-year-old girl with probable SoJIA who presented
      with MAS. She did not respond to pulse methyl prednisolone and Cyclosporine A
      (CsA). She also failed to respond to intravenous immunoglobulin (IVIG) therapy.
      Etanercept was started, based on the observation of increased serum levels of
      tumor necrosis factor-alpha (TNF-alpha) in patients with MAS. Her condition
      improved following etanercept, suggesting that etanercept might have a
      therapeutic role in resistant MAS.

PMID- 16900489
TI  - Flooding in GROMACS: accelerated barrier crossings in molecular dynamics.
AB  - The major bottleneck of today's atomistic molecular dynamics (MD) simulations is
      that because of the enormous computational effort involved, only processes at
      nanoseconds to microseconds time scales or faster can be studied directly.
      Unfortunately, apart from a few exceptions, relevant processes, such as chemical
      reactions or many large scale conformational transitions in proteins, occur at
      slower time scales and therefore are currently far out of reach for conventional
      MD. The flooding technique addresses this problem by inclusion of a flooding
      potential into the force field. This flooding potential locally destabilizes the
      educt state and thereby significantly accelerates the escape from the initial
      energy well without affecting the reaction pathway. Here, we summarize the theory
      and method for the computational chemistry community and detail the
      implementation within the official version 3.3 of the freely available MD program
      package GROMACS. Two examples shall demonstrate the application of flooding to
      accelerate conformational transitions and chemical reactions. The second example
      was carried out within a QM/MM framework.

PMID- 16900490
TI  - An algorithm for three-dimensional Voronoi S-network.
AB  - The paper presents an algorithm for calculating the three-dimensional Voronoi
      Delaunay tessellation for an ensemble of spheres of different radii (additively
      weighted Voronoi diagram). Data structure and output of the algorithm is oriented
      toward the exploration of the voids between the spheres. The main geometric
      construct that we develop is the Voronoi S-network (the network of vertices and
      edges of the Voronoi regions determined in relation to the surfaces of the
      spheres). General scheme of the algorithm and the key points of its realization
      are discussed. The principle of the algorithm is that for each determined site of
      the network we find its neighbor sites. Thus, starting from a known site of the
      network, we sequentially find the whole network. The starting site of the network
      is easily determined based on certain considerations. Geometric properties of
      ensembles of spheres of different radii are discussed, the conditions of
      applicability and limitations of the algorithm are indicated. The algorithm is
      capable of working with a wide variety of physical models, which may be
      represented as sets of spheres, including computer models of complex molecular
      systems. Emphasis was placed on the issue of increasing the efficiency of
      algorithm to work with large models (tens of thousands of atoms). It was
      demonstrated that the experimental CPU time increases linearly with the number of
      atoms in the system, O(n).

PMID- 16900491
TI  - Second derivatives in generalized Born theory.
AB  - Generalized Born solvation models offer a popular method of including
      electrostatic aspects of solvation free energies within an analytical model that
      depends only upon atomic coordinates, charges, and dielectric radii. Here, we
      describe how second derivatives with respect to Cartesian coordinates can be
      computed in an efficient manner that can be distributed over multiple processors.
      This approach makes possible a variety of new methods of analysis for these
      implicit solvation models. We illustrate three of these methods here: the use of
      Newton-Raphson optimization to obtain precise minima in solution; normal mode
      analysis to compute solvation effects on the mechanical properties of DNA; and
      the calculation of configurational entropies in the MM/GBSA model. An
      implementation of these ideas, using the Amber generalized Born model, is
      available in the nucleic acid builder (NAB) code, and we present examples for
      proteins with up to 45,000 atoms. The code has been implemented for parallel
      computers using both the OpenMP and MPI environments, and good parallel scaling
      is seen with as many as 144 OpenMP processing threads or MPI processing tasks.

PMID- 16900492
TI  - Computational study of the process of hydrogen bond breaking: the case of the
      formamide-formic acid complex.
AB  - MP2/6-311++G(d,p) and B3LYP/6-311++G(d,p) quantum calculations are used to study
      the formamide-formic acid complex (FFAC), a system bound by two hydrogen bonds, N
      -H...O and O--H...O, that forms a bond ring at equilibrium. When the
      intermolecular separation between monomers R increases, this ring opens at a
      distance for which the weaker N--H...O bond breaks remaining the stronger O-
      H...O bond. The computational study characterizes that process addressing changes
      of interaction energy DeltaE, structure and properties of the electron density
      rho(r) as well as spatial distributions of rho(r), the electrostatic potential
      U(r), and the electron localization function eta(r). It is shown that the spatial
      derivatives of DeltaE, the topology of rho(r), and qualitative changes noticed in
      U(r) = 0 isocontours allow to identify a precise distance R for which one can say
      the N--H...O hydrogen bond has broken. Both levels of theory predict essentially
      the same changes of structure and electron properties associated to the process
      of breaking and virtually identical distances at which it takes place.

PMID- 16900494
TI  - Quantum mechanical calculation of the effects of stiff and rigid constraints in
      the conformational equilibrium of the alanine dipeptide.
AB  - If constraints are imposed on a macromolecule, two inequivalent classical models
      may be used: the stiff and the rigid one. This work studies the effects of such
      constraints on the conformational equilibrium distribution (CED) of the model
      dipeptide HCO-L-Ala-NH(2)without any simplifying assumption. We use ab initio
      quantum mechanics calculations including electron correlation at the MP2 level to
      describe the system, and we measure the conformational dependence of all the
      correcting terms to the naive CED based in the potential energy surface that
      appear when the constraints are considered. These terms are related to mass
      metric tensors determinants and also occur in the Fixman's compensating
      potential. We show that some of the corrections are non-negligible if one is
      interested in the whole Ramachandran space. On the other hand, if only the
      energetically lower region, containing the principal secondary structure
      elements, is assumed to be relevant, then, all correcting terms may be neglected
      up to peptides of considerable length. This is the first time, as far as we know,
      that the analysis of the conformational dependence of these correcting terms is
      performed in a relevant biomolecule with a realistic potential energy function.

PMID- 16900493
TI  - Minimum sequence requirements for selective RNA-ligand binding: a molecular
      mechanics algorithm using molecular dynamics and free-energy techniques.
AB  - In vitro evolution techniques allow RNA molecules with unique functions to be
      developed. However, these techniques do not necessarily identify the simplest RNA
      structures for performing their functions. Determining the simplest RNA that
      binds to a particular ligand is currently limited to experimental protocols.
      Here, we introduce a molecular-mechanics based algorithm employing molecular
      dynamics simulations and free-energy methods to predict the minimum sequence
      requirements for selective ligand binding to RNA. The algorithm involves
      iteratively deleting nucleotides from an experimentally determined structure of
      an RNA-ligand complex, performing energy minimizations and molecular dynamics on
      each truncated structure, and assessing which truncations do not prohibit RNA
      binding to the ligand. The algorithm allows prediction of the effects of sequence
      modifications on RNA structural stability and ligand-binding energy. We have
      implemented the algorithm in the AMBER suite of programs, but it could be
      implemented in any molecular mechanics force field parameterized for nucleic
      acids. Test cases are presented to show the utility and accuracy of the
      methodology.

PMID- 16900495
TI  - Variation of atomic charges on proton transfer in strong hydrogen bonds: the case
      of anionic and neutral imidazole-acetate complexes.
AB  - The variation of atomic charges upon proton transfer in hydrogen bonding
      complexes of 4-methylimidazole, in both neutral and protonated cationic forms,
      and acetate anion, is investigated. These complexes model the histidine (neutral
      and protonated)-aspartate pair present in active sites of proteases where strong
      N--H...O hydrogen bonds are formed. Three procedures (Merz-Kollman scheme,
      Natural Population Analysis, and Atoms in Molecules Method) are used to compute
      atomic charges and explore their variation upon H-transfer in the gas phase and
      in the presence of two continuum media with dielectric constants 5 (protein
      interiors) and 78.39 (water). The effect of electron correlation was also studied
      by comparing Hartree-Fock and MP2 results for both complexes in the gas phase.
      Greater net charge interchanged upon H-transfer is observed in the anionic
      complex with respect to the neutral complex. Raising the polarity of the medium
      increases the amount of net charge transfer in both complexes, although the
      neutral system exhibits a larger sensitivity to the presence of solvent. Charge
      transfer associated to N--H...O and N...H--O bonds reveal the ionic contribution
      to the interaction depending on the number of charged subunits but the presence
      of solvent affects little this quantity. The lack of electron correlation
      overestimates all the charges as well as their variations and so uncorrelated
      calculations should be avoided.

PMID- 16900496
TI  - Accurate evaluation of the absorption maxima of retinal proteins based on a
      hybrid QM/MM method.
AB  - Here we improved our hybrid QM/MM methodology (Houjou et al. J Phys Chem B 2001,
      105, 867) for evaluating the absorption maxima of photoreceptor proteins. The
      renewed method was applied to evaluation of the absorption maxima of several
      retinal proteins and photoactive yellow protein. The calculated absorption maxima
      were in good agreement with the corresponding experimental data with a
      computational error of <10 nm. In addition, our calculations reproduced the
      experimental gas-phase absorption maxima of model chromophores (protonated all
      trans retinal Schiff base and deprotonated thiophenyl-p-coumarate) with the same
      accuracy. It is expected that our methodology allows for definitive
      interpretation of the spectral tuning mechanism of retinal proteins.

PMID- 16900497
TI  - Overexpression of PRDM16 in the presence and absence of the RUNX1/PRDM16 fusion
      gene in myeloid leukemias.

PMID- 16900498
TI  - Considering human-primate transmission of measles virus through the prism of risk
      analysis.
AB  - Measles is a respiratory virus that is endemic to humans. Human-nonhuman primate
      (NHP) transmission of the measles virus has been shown to cause significant
      morbidity and mortality in NHP populations. We investigated serological evidence
      of exposure to measles virus in two free-ranging populations of macaques at the
      Bukit Timah (BTNR) and Central Catchment Nature (CCNR) reserves in Singapore and
      the Swoyambhu Temple in Katmandu, Nepal. At BTNR/CCNR none of the 38 macaques
      (Macaca fascicularis) sampled were seropositive for antibodies to measles virus.
      In contrast, at Swoyambhu 100% (n = 39) of the macaques (M. mulatta) sampled were
      seropositive for antibodies to the measles virus. Here the contrasting
      seroprevalences of the two sites are analyzed using risk analysis. These case
      studies show how risk analysis can be used to approach the phenomenon of cross
      species pathogen transmission.

PMID- 16900499
TI  - Using retrospective health data from the Gombe chimpanzee study to inform future
      monitoring efforts.
AB  - Disease outbreaks, either in isolation or in concert with other risk factors, can
      pose serious threats to the long-term persistence of mammal populations, and
      these risks become elevated as population size decreases and/or population
      isolation increases. Many chimpanzee study sites are increasingly isolated by
      loss of habitat due to human encroachment, and managers of parks that contain
      chimpanzees perceive that disease outbreaks have been and continue to be
      significant causes of mortality for chimpanzees. Major epidemics at Gombe
      National Park include suspected polio in 1966; respiratory diseases in 1968,
      1987, 1996, 2000, and 2002; and sarcoptic mange in 1997. These outbreaks have led
      park managers and researchers working in Gombe to conclude that disease poses a
      substantial risk to the long-term survival of Gombe's chimpanzee population. We
      surveyed behavioral data records spanning 44 years for health-related data and
      found a combination of standardized and nonstandardized data for the entire
      period. Here we present the types of data found during the survey, discuss the
      usefulness of these data in the context of risk assessment, and describe how our
      current monitoring effort at Gombe was designed based on our findings.

PMID- 16900500
TI  - Anthrax in Western and Central African great apes.
AB  - During the period of December 2004 to January 2005, Bacillus anthracis killed
      three wild chimpanzees (Pan troglodytes troglodytes) and one gorilla (Gorilla
      gorilla gorilla) in a tropical forest in Cameroon. While this is the second
      anthrax outbreak in wild chimpanzees, this is the first case of anthrax in
      gorillas ever reported. The number of great apes in Central Africa is
      dramatically declining and the populations are seriously threatened by diseases,
      mainly Ebola. Nevertheless, a considerable number of deaths cannot be attributed
      to Ebola virus and remained unexplained. Our results show that diseases other
      than Ebola may also threaten wild great apes, and indicate that the role of
      anthrax in great ape mortality may have been underestimated. These results
      suggest that risk identification, assessment, and management for the survival of
      the last great apes should be performed with an open mind, since various
      pathogens with distinct characteristics in epidemiology and pathogenicity may
      impact the populations. An animal mortality monitoring network covering the
      entire African tropical forest, with the dual aims of preventing both great ape
      extinction and human disease outbreaks, will create necessary baseline data for
      such risk assessments and management plans.

PMID- 16900502
TI  - Human culture and monkey behavior: Assessing the contexts of potential pathogen
      transmission between macaques and humans.
AB  - An in-depth understanding of the contexts and patterns of human-macaque
      interactions can play an important role in assessing and managing the potential
      for pathogen transmission. The Padangtegal Monkey Forest in Bali, Indonesia, and
      the Upper Rock Nature Reserve in Gibraltar are two sites that have been
      relatively well studied in regard to human-macaque interactions. This article
      presents an overview of interaction patterns between humans and macaques at these
      sites along with a description of the cultural, demographic, and contextual
      differences between local and nonlocal humans at the sites. Differences in these
      two sites' interaction patterns included bite rates, the role of food in
      aggressive interactions, and the context in which the interactions took place.
      Similarities included overrepresentation by adult male macaques in interactions
      and a substantial impact by local cultural and demographic factors. These
      similarities and differences are interpreted as resulting from differences in
      macaque species and behaviors, and human demography, culture, and behavioral
      patterns.

PMID- 16900501
TI  - Disease risk analysis: a tool for primate conservation planning and decision
      making.
AB  - Concern about emerging and re-emerging diseases plays an increasing role in
      conservation and management of both captive and free-ranging nonhuman primates
      (NHPs). Managers and policy makers must formulate conservation plans in an arena
      plagued by uncertainty, complexity, emotion, and politics. The risk analysis
      paradigm provides a framework that brings together scientists and policy experts
      to make better decisions for both people and animals. Risk analysis is a
      multidisciplinary, science-based process that provides an organized and logical
      approach for incorporating scientific information into policy development in the
      real world. By blending four specific goal-oriented stages-hazard identification,
      risk assessment, risk management, and risk communication-one can logically assess
      the probability that an adverse event, such as the introduction of an emerging
      disease into a naive population, will occur. The following is a review of this
      process as it pertains to NHP conservation and risks associated with infectious
      diseases.

PMID- 16900503
TI  - Clinical response Decision Tree for the Mountain Gorilla (Gorilla beringeii) as a
      model for great apes.
AB  - Disease is one of the main threats to the remaining great ape populations of the
      world. The decision to intervene in the health of the great apes for population
      sustainability is controversial. Humans' increasing negative influence on great
      ape health has mandated the reevaluation of current management policies. The
      Mountain Gorilla Veterinary Project (MGVP) has been making health intervention
      decisions since 1986. The decision to intervene has often been made subjectively
      due to poorly defined criteria that are often influenced by emotion. This paper
      provides a consistent framework for evidence-based health intervention decision
      making. The decision tree is a five-tier process consisting of routine sentinel
      health observation, intensive follow-up veterinary health observation, outbreak
      assessment, risk assessment, and risk management. Although this paper focuses on
      the mountain gorillas, it serves as a basis for evidence-based decision-making in
      other species.

PMID- 16900504
TI  - Risk assessment: A model for predicting cross-species transmission of simian
      foamy virus from macaques (M. fascicularis) to humans at a monkey temple in Bali,
      Indonesia.
AB  - Contact between humans and nonhuman primates (NHPs) frequently occurs at monkey
      temples (religious sites that have become associated with free-ranging
      populations of NHPs) in Asia, creating the potential for NHP-human disease
      transmission. In March 2003 a multidisciplinary panel of experts participated in
      a workshop designed to model the risk of NHP-human pathogen transmission. The
      panel developed a risk assessment model to describe the likelihood of cross
      species transmission of simian foamy virus (SFV) from temple macaques (Macaca
      fascicularis) to visitors at monkey temples. SFV is an enzootic simian retrovirus
      that has been shown to be transmitted from NHPs to humans. In operationalizing
      the model field data, laboratory data and expert opinions were used to estimate
      the likelihood of SFV transmission within this context. This model sets the stage
      for a discussion about modeling as a risk assessment tool and the kinds of data
      that are required to accurately predict transmission.

PMID- 16900505
TI  - Disease risk analysis: A paradigm for using health-based data to inform primate
      conservation and public health.
AB  - Risk analysis is a multidisciplinary process used to evaluate existing knowledge
      in order to prioritize risks associated with the spread of disease. A principle
      aim of risk analysis is to facilitate the development of cost-effective
      management strategies. Risk analysis calls for a multidisciplinary approach to
      piece together and integrate the numerous factors that influence disease
      transmission. The seven papers included in this volume of AJP present current
      primatological research as viewed through the prism of risk analysis. Issues such
      as interspecies disease transmission, public health, and conservation of
      endangered species are addressed, and risk analysis is put forward as a possible
      paradigm to promote understanding of infectious disease and its impact on
      nonhuman primate and human populations.

PMID- 16900506
TI  - Feeding behavior of lactating brown lemur females (Eulemur fulvus) in Mayotte:
      influence of infant age and plant phenology.
AB  - Altmann [Baboon Mothers and Infants, University of Chicago Press, 1980] and
      Dunbar and Dunbar [Animal Behavior 36:970-980, 1988] provided a model that
      predicts the amount of time spent feeding by lactating baboon females, as related
      to infant age. Dunbar's model further suggests that food quality affects the
      amount of time that females devote to feeding activity, and is predictable from
      rainfall and temperature data. In this study the model was tested with data
      recorded from births of the Mayotte brown lemur from four maternal dyads (Eulemur
      fulvus). This study also examines the correlation between female activity budget,
      quantities of fresh plant matter ingested, and suckling duration using data
      collected from focal animal samples on the mother-infant dyads. The relationships
      among rainfall, food supply, and food quality were also tested. It appears that
      female brown lemurs do not devote more time to feeding during the infant growth
      period. The data show that female brown lemurs increased their food intake during
      the early-lactating period when the frequency of suckling is the highest, and
      before infants begin to eat substantial amounts of solid foods. Thus, the
      frequency of feeding reflects the cost of lactation better than suckling
      duration. Furthermore, females did not appear to select foods according to their
      availability or rainfall levels. I hypothesize that the lack of convergence
      between lemur data and baboon observations is due to differences between their
      respective environments and their feeding ecology. These data also indicate that
      the most significant lactating cost for the brown lemur occurs during the early
      lactation period.

PMID- 16900507
TI  - Social influences on the development of foraging behavior in free-living common
      marmosets (Callithrix jacchus).
AB  - In this study we investigated the extent and pattern of social influences (i.e.,
      the use of a conspecific as a model) on the foraging behavior of immature, wild
      common marmosets (Callithrix jacchus) as a function of the age of individuals. We
      compared the foraging activities and interactions with subadult and adult group
      members (older than 15 months) of young infants (1-2 months old), older infants
      (3-4 months old), and juveniles (5-10 months old). In addition to measuring the
      intensities of model-independent foraging (MIF) and merely paying attention to
      the model's foraging activities, we examined the frequencies of three types of
      model-dependent foraging (MDF): "follow the model", "manipulate the same object",
      and "forage together". We found that older infants were the most attentive and
      most socially-influenced foragers among the three age categories in absolute
      terms, but were not more attentive than young infants given their low foraging
      activity. Juveniles, in contrast, tended to have reduced overall foraging
      intensity compared to infants, but showed relatively more MDF in cases in which
      they observed subadult or adult models. Female models appeared to be more
      attractive than male models. These findings suggest that infants are generally
      more attentive to the foraging behavior of subadults and adults than juveniles,
      with the latter being more influenced when they had observed a model before.
      These subtle age-dependent effects of social foraging not only extend the
      assumption that young primates seek information from adults, they also suggest a
      complex interplay among physical and cognitive maturation, independence, and
      social dynamics.

PMID- 16900508
TI  - Propagation of plant viruses in hairy root cultures: a potential method for in
      vitro production of epitope vaccines and foreign proteins.
AB  - Hairy roots were used as an in vitro culture system for the propagation of wild
      type and transgenic plant viruses. Tobacco mosaic virus (TMV) was added to the
      liquid culture medium at the same time as root inoculation. Hairy root growth was
      unaffected by viral infection. Maximum concentrations of TMV in Nicotiana
      benthamiana hairy roots were 1-2 orders of magnitude greater than in suspended N.
      benthamiana cells and reached levels of 1-2 mg g(-1) dry weight or 20-28% total
      soluble protein. Virus accumulated in the roots initially with a constant
      doubling time of about 1.0 day; subsequent reductions in viral growth rate were
      correlated with a significant decline in infectivity relative to the inoculum
      virus. The morphological integrity of the viral particles was maintained during
      propagation in hairy roots. The contribution to the overall viral titer of
      passive association of virus with the biomass, for example, by surface
      adsorption, was negligible compared with active viral replication. N. benthamiana
      hairy roots were also infected with a TMV-based viral vector developed to express
      green fluorescent protein (GFP). This vector was about 260-fold less infectious
      than wild-type TMV and accumulated much more slowly in the roots. Maximum levels
      of TMV-GFP in the biomass were about 65-fold lower than for TMV. This work
      demonstrates that hairy root cultures are a feasible means for in vitro
      propagation of wild-type and transgenic plant viruses under conditions that allow
      a high degree of environmental containment and control.

PMID- 16900510
TI  - Autologous diaphragm reconstruction with the pedicled latissimus dorsi flap.
AB  - The latissimus dorsi (LD) muscle has been previously described to repair
      diaphragmatic defects, but as a "reverse" flap, relying on secondary blood supply
      from the perforating lumbar vessels rather than primary inflow from the dominant
      thoracodorsal artery. We report resection of a retroperitoneal synovial sarcoma,
      with reconstruction of the hemidiaphragm using the LD rotated on its primary
      neurovascular bundle. By using the dominant pedicle, the vascularity of the flap
      is improved, minimizing the chance of flap tip loss. Maintaining an intact nerve
      supply prevents atrophy. As the distal origin of the LD is broad and flat, it is
      ideally suited for diaphragm repair. A latissimus-sparing thoracotomy incision is
      required to enable this method of diaphragm reconstruction.

PMID- 16900509
TI  - Distinctive clinicopathological features of Ki-ras mutated colorectal cancers.
AB  - BACKGROUND AND OBJECTIVES: We explored the relationship between the mutation
      pattern of Ki-ras and the clinicopathological features of colorectal cancers
      (CRCs). METHODS: Relationships between clinicopathological parameters and Ki-ras
      mutation status were analyzed in 255 CRC patients using the chi-square and
      student t-tests. Kaplan-Meier survival curves were compared using the log-rank
      test. RESULTS: Ki-ras mutation occurred in 43.9% of tumors, and 83% affected
      codon 12. The most frequent mutations were GGT->GAT (Gly->Asp) (37.5%), followed
      by GGT->GTT (Gly->Val) (31.3%), both in codon 12. The frequency of Ki-ras
      mutation was similar for different tumor stages (38.2-47.8%). The mucin component
      of tumors was significantly associated with Ki-ras mutation. The 4-year overall
      and disease-free survival was 61% and 54%, respectively, for patients with Ki-ras
      mutated tumors, and 73% and 60% for patients with nonmutated tumors (not
      statistically significant). Patients with Ki-ras mutated tumors had lower plasma
      folate (24 ng/dl) than those bearing nonmutated tumors (37 ng/dl). Patients with
      G->T Ki-ras mutations had the lowest folate level (22 ng/dl), followed by those
      with G->A mutations (25 ng/dl). CONCLUSIONS: Ki-ras mutated colorectal tumors
      have a higher mucin production and higher differentiation, and are associated
      with lower plasma folate levels and a relatively poorer disease outcome.

PMID- 16900511
TI  - Level-adjusted perioperative risk of sacral amputations.
AB  - BACKGROUND AND OBJECTIVES: Sacral amputations above the S2 body often involve
      increased surgical complexity leading to long-term morbidity. The purpose of this
      study was to determine whether proximal sacral amputations have substantially
      higher perioperative morbidity compared with more distal sacral amputations.
      METHODS: We evaluated the effect of sacral amputation level on perioperative
      outcomes within 90 days of surgery. Outcome measures included blood loss,
      intensive care unit (ICU) and hospital stay, hospital cost, and incidence of a
      major and minor morbidity. Survival analyses were adjusted for the level of
      resection and histological appearance. RESULTS: Thirteen proximal and 14 distal
      resections were performed. In comparing proximal versus distal resections, median
      estimated blood loss was 4 L versus 1 L (P < 0.001), ICU stay was 4 days versus 0
      days (P = 0.012), hospital stay was 19 days versus 8 days (P = 0.001), hospital
      cost was 28,800 dollars versus 7,500 dollars (P = 0.003), with one or more major
      complications in 85% versus 29% (P = 0.011). Survival analysis demonstrated that
      the sacral resection level did not influence survival (P = 0.936), whereas the
      type of tumor did influence survival (P = 0.012). CONCLUSION: Tumor resections
      above S2 demonstrate increased perioperative morbidity, suggesting that proximal
      osteotomies be reserved for patients with a realistic cure potential.

PMID- 16900513
TI  - Hypoxia inducible factors 1alpha and 2alpha are associated with VEGF expression
      and angiogenesis in gallbladder carcinomas.
AB  - AIMS: To investigate the significance of the hypoxia inducible factors HIF-1alpha
      and HIF-2alpha in gallbladder adenocarcinomas and their relation to angiogenesis
      and to the expression of VEGF, an angiogenic factor transcriptionally regulated
      by HIFalphas. METHODS: HIF-1alpha and 2alpha expression was assessed
      immunohistochemically in 60 patients with early gallbladder adenocarcinomas,
      treated with surgery alone. In addition, the vascular density (VD) and the
      expression of the angiogenic factors VEGF and thymidine phosphorylase (TP) were
      examined. The results were correlated with clinico-pathological features and
      prognosis. RESULTS: Overexpression of HIF-1alpha and 2alpha was significantly
      associated with increased tumor angiogenesis and VEGF expression, while HIF
      2alpha was linked with upregulation of TP. None of these factors were associated
      with T-stage and tumor grade. Although HIFs did not relate significantly with
      prognosis, patients with HIF-1/2 expression who failed to switch-on VEGF or
      intratumoral angiogenesis had a favorable outcome. CONCLUSION: Hypoxia inducible
      factors are upregulated in a large proportion of gallbladder adenocarcinomas, a
      feature strongly related to increased expression of VEGF and intensified
      angiogenesis.

PMID- 16900512
TI  - Generation of a conditional null allele of jumonji.
AB  - The jumonji (jmj) gene plays important roles in multiple organ development in
      mouse, including cardiovascular development. Since JMJ is expressed widely during
      mouse development, it is essential that conditional knockout approaches be
      employed to ablate JMJ in a tissue-specific manner to identify the cell lineage
      specific roles of JMJ. In this report, we describe the establishment of a jmj
      conditional null allele in mice by generating a loxP-flanked (floxed) jmj allele,
      which allows the in vivo ablation of jmj via Cre recombinase-mediated deletion.
      Gene targeting was used to introduce loxP sites flanking exon 3 of the jmj allele
      to mouse embryonic stem cells. Our results indicate that the jmj floxed allele
      converts to a null allele in a heart-specific manner when embryos homozygous for
      the floxed jmj allele and carrying the alpha-myosin heavy chain promoter-Cre
      transgene were analyzed by Southern and Northern blot analyses. Therefore, this
      mouse line harboring the conditional jmj null allele will provide a valuable tool
      for deciphering the tissue and cell lineage specific roles of JMJ.

PMID- 16900514
TI  - Therapeutic strategy for patients with pN0 gastric carcinoma.
AB  - BACKGROUND AND OBJECTIVES: The prognosis for patients with pN0 gastric cancer is
      moderately hopeful (expected 5-year survival: 80%). However, the relevant
      prognostic factors and most appropriate surveillance protocol have not been
      identified. METHODS: We investigated 733 gastric cancer patients without lymph
      node metastasis for prognostic factors by uni- and multi-variate analysis and by
      documenting causes of death and recurrence patterns. RESULTS: Univariate analysis
      revealed that age, tumor location, macroscopic appearance, tumor diameter,
      invasion depth, lymphatic invasion, and venous invasion affected prognosis.
      Multivariate analysis showed that age (> or = 60 years), ill-defined macroscopic
      appearance, and undifferentiated histological type independently reduced survival
      rates. Age (> or = 60 years) and undifferentiated histological type adversely
      influenced prognosis in 507 early gastric cancer patients whereas ill-defined
      macroscopic appearance adversely affected prognosis in 226 advanced cancer
      patients. Recurrence patterns in these patients were similar to those produced by
      lymph node metastasis. The predominant recurrence pattern was peritoneal
      dissemination, observed 2-3 years post-resection. CONCLUSIONS: This study
      identified adverse prognostic factors in pN0 gastric cancer patients. Randomized
      controlled studies of adjuvant chemotherapy are necessary to assess whether such
      therapy is beneficial for patients with adverse prognostic factors.

PMID- 16900515
TI  - Interpectoral approach to dissection of the axillary apex: an elegant and
      effective approach.
AB  - BACKGROUND: Axillary dissection is the gold standard for treatment of the axilla.
      It provides important prognostic information, accurately stages the axilla, and
      has the lowest recurrence rate among all modalities. In today's age of
      conservation surgery, the axilla is often addressed through a cosmetically
      acceptable small incision with limited access, thereby making clearance of the
      level III nodes difficult. METHODS: We describe a method of apical lymph node
      dissection through the interpectoral plane, which effectively clears the apex
      despite the constraints of limited exposure. RESULTS: This method has been used
      in nearly 5,000 axillary dissections performed at our institute, with excellent
      results. It preserves the innervation of the pectoral muscles and affords access
      to the interpectoral nodes. CONCLUSIONS: Our method has a short learning curve,
      provides good exposure of a difficult area and consistently provides a good yield
      of nodes.

PMID- 16900516
TI  - Peritoneal lavage with distilled water during liver resection in patients with
      spontaneously ruptured hepatocellular carcinomas.
AB  - Spontaneously rupture of hepatocellular carcinoma is a life threatening and worse
      prognosis. Not only the lower rate of resection and hemodynamic unstable, but
      also the hepatic failure and recurrence. Distilled water irrigation had been
      applied in several cancer surgeries including colon, stomach, breast, ovary, and
      bladder; thus had good results in lowering the tumor spreading. We applied
      distilled water peritoneal lavage after liver resection in patients with
      spontaneous rupture of hepatocellular carcinoma to define the influence of
      prognosis. Thirteen patients with spontaneous ruptured hepatocellular carcinoma
      underwent distilled water peritoneal lavage after curative liver resection (Group
      A). Nineteen patients with spontaneous ruptured hepatocellular carcinoma did not
      undergo distilled water peritoneal lavage after curative liver resection (Group
      B). There were 11 patients of tumor recurrence in Group B; 2 in Group A. The mean
      disease-free time of Group B was 2.05 +/- 0.74 years; for Group A it was 3.59 +/-
      0.60 (P = 0.045). Peritoneal lavage in this series resulted in significantly
      better survival time for the patients in Group A (P = 0.0158). That implies
      distilled water peritoneal lavage during liver resection would retard the tumor
      recurrence and further improve the survival rate in patients with spontaneously
      ruptured hepatocellular carcinoma.

PMID- 16900517
TI  - Dlx5 and Dlx6 homeobox genes are required for specification of the mammalian
      vestibular apparatus.
AB  - The mammalian inner ear is a complex organ that develops from a surface ectoderm
      into distinct auditory and vestibular components. Congenital malformation of
      these two components resulting from single or multiple gene defects is a common
      clinical occurrence and is observed in patients with split hand/split foot
      malformation, a malformation which is phenocopied by Dlx5/6 null mice. Analysis
      of mice lacking Dlx5 and Dlx6 homeobox genes identified their restricted and
      combined expression in the otic epithelium as a crucial regulator of vestibular
      cell fates. Otic induction initiates without incident in Dlx5/6(-/-) embryos, but
      dorsal otic derivatives including the semicircular ducts, utricle, saccule, and
      endolymphatic duct fail to form. Dlx5 and Dlx6 seem to influence vestibular cell
      fates by restricting Pax2 and activating Gbx2 and Bmp4 expression domains. Given
      their proximity to the disease locus and the observed phenotype in Dlx5/6 null
      mice, Dlx5/6 are likely candidates to mediate the inner ear defects observed in
      patients with split hand/split foot malformation.

PMID- 16900518
TI  - Significance of micrometastases on the survival of women with T1 breast cancer.
AB  - BACKGROUND: The most important factor in predicting survival among women with
      newly diagnosed breast cancer is the status of the axillary lymph nodes. Although
      straightforward to define, the impact of micrometastases on survival remains to
      be completely determined. METHODS: A review of data from the Surveillance,
      Epidemiology, and End Results Program of the National Cancer Institute was
      performed using 43,921 cases diagnosed from January 1988 through December 2001.
      Among women with invasive breast carcinomas <or=2 cm undergoing a resection of
      the primary malignancy and an axillary lymph node dissection, there were 42,197
      cases without lymph node metastases and 1724 cases with micrometastases. Survival
      differences among these 2 groups were evaluated and are reported here. RESULTS:
      Survival at 12 years was modestly affected by the presence of either solitary
      (5.0%) or multiple lymph nodes (3.6%) with micrometastases when compared with
      lymph node-negative cases. In subgroup analyses, the decreased survival
      associated with micrometastases was inconsistent. The most significant survival
      disadvantage associated with micrometastases was found in cases with Grade 3
      carcinomas. CONCLUSIONS: The modest and variable impact of micrometastases on
      long-term survival indicates that micrometastases are an important, but not a
      dominant, prognostic indicator.

PMID- 16900519
TI  - Follicular variant of papillary thyroid carcinoma: a clinicopathologic study of a
      problematic entity.
AB  - BACKGROUND: There is continuous debate regarding the optimal classification,
      prognosis, and treatment of the follicular variant of papillary thyroid carcinoma
      (FVPTC). The objective of this study was to assess the behavior of FVPTC,
      especially its encapsulated form, and shed more light on its true position in the
      classification scheme of well differentiated thyroid carcinoma. METHODS: All
      patients with FVPTC, follicular thyroid adenoma (FTA), and follicular thyroid
      carcinoma (FTC) who were diagnosed between 1980 and 1995 were reviewed and
      reclassified according to the currently accepted definition of FVPTC. The tumors
      were separated into encapsulated and nonencapsulated (infiltrative/diffuse)
      types. Encapsulated tumors were subdivided further into tumors with or without
      capsular/vascular invasion. These different subtypes of FVPTC were correlated
      with outcome and with other clinicopathologic parameters. RESULTS: After review
      by 4 pathologists, 78 patients were included in the study. Sixty-one of 78
      patients (78%) had encapsulated tumors (18 invasive, 43 noninvasive), and 17
      patients had nonencapsulated tumors (infiltrative/diffuse). The gender
      distribution, age at presentation, and tumor size did not differ between patients
      with encapsulated and nonencapsulated FVPTC. Patients who had encapsulated FVPTC
      had a significantly lower rate of marked intratumor fibrosis (18%), extrathyroid
      extension (5%), and positive margins (2%) compared with patients who had
      nonencapsulated tumors (88%, 65%, and 50% respectively; P < .0001). Regional
      lymph node metastases were present in 14 of 78 patients (18%), and no patients
      had distant metastases. The lymph node metastatic rate was significantly higher
      in patients who had nonencapsulated tumors (11 of 17 patients; 65%) compared with
      patients who had encapsulated neoplasms (3 of 61 patients; 5%; P < .0001). In
      addition, lymph node metastases were not detected in any noninvasive,
      encapsulated FVPTCs. With a median follow-up of 10.8 years, only 1 patient
      developed a recurrence, which occurred in an encapsulated FVPTC that had numerous
      invasive foci. None of the patients with noninvasive, encapsulated FVPTCs
      developed recurrences, including 31 patients who underwent lobectomy alone, with
      a median follow-up of 11.1 years. CONCLUSIONS: FVPTC appeared to be a
      heterogeneous disease composed of 2 distinct groups: an infiltrative/diffuse
      (nonencapsulated) subvariant, which resembles classic papillary carcinoma in its
      metastatic lymph node pattern and invasive growth, and an encapsulated form,
      which behaves more like FTA/FTC. Patients who had noninvasive, encapsulated
      FVPTCs did not develop lymph node metastases or recurrences and could be treated
      by lobectomy alone. If the current findings are confirmed, then strong
      consideration should be given to reclassifying encapsulated FVPTC as an entity
      that is close to the FTA/FTC class of tumors.

PMID- 16900520
TI  - Effect of non-feeding period length on the intermittent operation of UASB
      reactors treating dairy effluents.
AB  - Recent environmental concerns have prompted a re-evaluation of conventional
      management strategies and refueled the search of innovative waste management
      practices. In this sense, the anaerobic digestion of both fat and the remaining
      complex organic matter present in dairy wastewaters is attractive, although the
      continuous operation of high rate anaerobic processes treating this type of
      wastewaters causes the failure of the process. This work accesses the influence
      of non-feeding period length on the intermittent operation of mesophilic UASB
      reactors treating dairy wastewater, in order to allow the biological degradation
      to catch up with adsorption phenomenon. During the experiments, two UASB reactors
      were subject to three organic loading rates, ranging from 6 to 12 g(COD) x L(-1)
      x d(-1), with the same daily load applied to both reactors, each one with a
      different non-feeding period. Both reactors showed good COD removal efficiencies
      (87-92%). A material balance for COD in the reactors during the feeding and non
      feeding periods showed the importance of the feedless period, which allowed the
      biomass to degrade substrate that was accumulated during the feeding period. The
      reactor with the longest non-feeding period had a better performance, which
      resulted in a higher methane production and adsorption capacity for the same
      organic load applied with a consequent less accumulation of substrate into the
      biomass. In addition, both reactors had a stable operation for the organic load
      of 12 g(COD) x L(-1) x d(-1), which is higher than the maximum applicable load
      reported in literature for continuous systems (3-6 g(COD) x L(-1) x d(-1)).

PMID- 16900521
TI  - Buccal plate excision for buccal paramandibular spread.
AB  - Cancer of buccal gingival sulcus lie in close proximity to mandible but tend to
      invade bone late in the course of disease. Segmental mandibulectomy advocated for
      these tumors results in cosmetic disfigurement and functional impairment. We, for
      the first time, describe a mandibular preservation alternative, in form of buccal
      cortical plate excision, for these tumors.

PMID- 16900522
TI  - Cystatin C in cerebrospinal fluid and multiple sclerosis.
AB  - OBJECTIVE: A recent study using surface-enhanced laser desorption/ionization time
      of-flight analysis of cerebrospinal fluid identified a 12.5 kDa truncated isoform
      of cystatin C (CysC) as a specific biomarker for multiple sclerosis (MS).
      METHODS: Surface-enhanced laser desorption/ionization time-of-flight analysis of
      cerebrospinal fluid samples from 43 MS patients and 46 healthy control subjects.
      RESULTS: Full-length CysC (13.4 kDa) concentration was similar in MS and control
      samples. The 12.5 kDa CysC protein was produced from full-length CysC by N
      terminal cleavage during storage at -20 degrees C. INTERPRETATION: The 12.5 kDa
      CysC isoform is a storage-related artifact and is not useful as a diagnostic
      marker for MS.

PMID- 16900524
TI  - Kinetics of biodegradation of p-xylene and naphthalene and oxygen transfer in a
      novel airlift immobilized bioreactor.
AB  - The scope of this study included the biodegradation performance and the rate of
      oxygen transfer in a pilot-scale immobilized soil bioreactor system (ISBR) of 10
      L working volume. The ISBR was inoculated with an acclimatized population of
      contaminant degrading microorganisms. Immobilization of microorganisms on a non
      woven polyester textile developed the active biofilm, thereby obtaining
      biodegradation rates of 81 mg/L x h and 40 mg/L x h for p-xylene and naphthalene,
      respectively. Monod kinetic model was found to be suitable to correlate the
      experimental data obtained during the course of batch and continuous operations.
      Oxygen uptake and transfer rates were determined during the batch biodegradation
      process. The dynamic gassing-out method was used to determine the oxygen uptake
      rate (OUR) and volumetric oxygen mass transfer, K(L) a. The maximum volumetric
      OUR of 255 mg O(2)/L x h occurred approximately at 720-722 h after inoculation,
      when the dry weight of biomass concentration was 0.67 g/L.

PMID- 16900523
TI  - Clinical and pathologic outcome after radical prostatectomy for prostate cancer
      patients with a preoperative Gleason sum of 8 to 10.
AB  - BACKGROUND: Men with a biopsy Gleason sum of 8 to 10 are considered high-risk.
      The current study sought to identify whether there was a subset of men with high
      biopsy Gleason sums who would have a good pathologic and biochemical outcome with
      surgical monotherapy. To increase the generalizability of the findings, data were
      used from patients treated at 2 very different practice settings: a tertiary care
      referral center (Johns Hopkins Hospital) and multiple equal-access medical
      centers (Shared Equal Access Regional Cancer Hospital [SEARCH] Database).
      METHODS: The data were retrospectively reviewed from men with biopsy Gleason sums
      8 to 10 treated by radical prostatectomy at the Johns Hopkins Hospital (n = 220,
      3.8% of total cohort) and within the SEARCH Database (n = 149, 7.7% of total
      cohort). The preoperative clinical characteristics predicting unfavorable
      pathologic disease (nonorgan-confined and/or positive surgical margins) and time
      to biochemical recurrence were determined using logistic regression and Cox
      proportional hazards analysis, respectively. RESULTS: Favorable pathologic
      outcome (organ-confined and negative surgical margins) was observed in 21% of the
      men in the Johns Hopkins cohort and 41% from the SEARCH cohort. On multivariate
      analysis, higher serum prostate-specific antigen (PSA) was the only variable that
      significantly predicted an unfavorable pathologic outcome from both the Johns
      Hopkins (P = .047) and SEARCH cohorts (P = .002). The 5-year and 10-year
      estimated biochemical-free survival rates in the Johns Hopkins cohort were 40%
      (95% confidence interval [CI], 33-48%) and 27% (95% CI, 18-36%), respectively,
      and 32% (95% CI, 22-42%) and 28% (95% CI, 18-38%) in the SEARCH cohort,
      respectively. Among men with favorable pathologic findings, the 5- and 10-year
      estimated biochemical-free survival rates in the Johns Hopkins cohort were 79%
      (95% CI, 62-89%) and 50% (95% CI, 25-71%), respectively, and 49% (95% CI, 32-65%)
      and 49% (95% CI, 32-65%) in the SEARCH cohort, respectively. No single
      preoperative variable significantly predicted the risk of biochemical progression
      in both the SEARCH or Johns Hopkins cohorts. CONCLUSIONS: The majority of men
      with a biopsy Gleason sum of >or=8, regardless of where the patient is treated,
      had unfavorable pathologic disease and experienced a biochemical progression
      after radical prostatectomy. Even among men with organ-confined disease and
      negative surgical margins or pathologic Gleason sum <8, at least half of the men
      experienced a PSA recurrence. Patients with biopsy Gleason sum 8 to 10 cancers
      are good candidates for multimodal therapy. Whereas multimodal therapy has often
      meant radiation plus hormonal therapy, newer possibilities for multimodal therapy
      exist such as surgery with neoadjuvant or adjuvant chemohormonal therapy or
      surgery with adjuvant radiation.

PMID- 16900525
TI  - Phase II trial of pulse dactinomycin as salvage therapy for failed low-risk
      gestational trophoblastic neoplasia: a Gynecologic Oncology Group study.
AB  - BACKGROUND: The purpose of the study was to determine the activity and toxicity
      of pulse dactinomycin as salvage treatment of patients with low-risk gestational
      trophoblastic neoplasia (GTN) who failed methotrexate therapy. METHODS: Eligible
      patients had persistent/recurrent low-risk GTN defined by changes in serum human
      chorionic gonadotropin (hCG) levels (<10% fall over 3 consecutive weekly titers,
      >20% rise over the previous value, or a rise after attaining institutional normal
      [>5 mu/mL]); World Health Organization (WHO) score 2-6; Gynecologic Oncology
      Group (GOG) performance status 0-1; and previous treatment restricted to
      methotrexate. Dactinomycin administration was 1.25 mg/m2 intravenous (i.v.) every
      2 weeks until documented complete response (CR) or treatment failure. CR was
      defined as an institutional normal serum hCG level sustained for >or=4
      consecutive weeks; treatment failure was a <10% fall (3 assays over 4 weeks) or
      >20% rise (over previous value) in hCG serum level. Levels were monitored
      biweekly x 8 weeks beyond the first normal value, then monthly x 10. RESULTS:
      Five of 44 enrolled patients were ineligible due to choriocarcinoma and normal
      pretreatment serum hCG level (2 each), no history of methotrexate (1), and 1
      patient with documented phantom hCG syndrome was unevaluable. In all, 28 of 38
      (74%) evaluable patients attained CR. The median number of cycles was 4 (range, 2
      10). Severe toxicity was minimal, causing no patient to discontinue therapy. All
      treatment failures achieved a CR after receiving subsequent chemotherapy; 3
      patients also underwent hysterectomy. CONCLUSION: Pulse dactinomycin is an active
      regimen for patients with low-risk GTN who fail previous methotrexate therapy.

PMID- 16900526
TI  - Propagation of fluorescent viruses in growing plaques.
AB  - To study virus propagation, we have developed a method by which the propagation
      of the Lambda bacteriophage can be observed and quantified. This is done by
      creating a fusion protein of the capsid protein gpD and the enhanced yellow
      fluorescent protein (EYFP). We show that this fusion allows capsid formation and
      that the modified viruses propagate on a surface covered with host bacteria thus
      forming fluorescent plaques. The intensity of fluorescence in a growing plaque
      determines the distribution of phages. This provides a new tool to study the
      propagation of infection at the microscopic level.

PMID- 16900528
TI  - Can chymase-positive mast cells play a role in the progression of gastric cancer
      via angiogenesis?

PMID- 16900529
TI  - Risks of sacral amputations.

PMID- 16900530
TI  - Antivascular therapy of cancer metastasis.

PMID- 16900531
TI  - Which treatment for squamous cell carcinoma of the pharyngoesophageal junction?

PMID- 16900533
TI  - Expression of inducible nitric oxide synthase and cyclooxygenase-2 in
      angiogenesis and clinical outcome of human gastric cancer.
AB  - BACKGROUND AND OBJECTIVES: It has been recognized that inducible nitric oxide
      synthase (iNOS) and cyclooxygenase (COX-2) produce important endogenous factors
      of human tumors such as nitric oxide (NO) and prostaglandins, which is involved
      in the process of carcinogenesis and tumor progression. This study aimed to
      evaluate the association of clinicopathologic factors, microvessel density, and
      patient survival with the expression of iNOS and COX-2 in patients with gastric
      adenocarcinoma. MATERIALS AND METHODS: Seventy-nine specimens, resected from
      patients with gastric adenocarcinoma, were investigated by immunohistochemical
      stain against iNOS and COX-2. Microvessels were stained using anti-CD34 antibody
      and counted as microvessel density. RESULTS: Positive iNOS and COX-2 expressions
      were significantly correlated with microvessel density by multivariate analysis,
      respectively (P = 0.0127 vs. P = 0.0214). There was significant difference among
      the four groups (both iNOS and COX-2 positive, iNOS positive only, COX-2 positive
      only, and both negative) in serosal invasion (P = 0.038), lymph node metastasis
      (P = 0.038), Helicobacter pylori infection (P = 0.025), vascular invasion (P =
      0.035), and microvessel density (P = 0.019). In patients with gastric cancer that
      co-expressed iNOS and COX-2, prognosis was significantly poorer than in those
      that expressed either iNOS or COX-2, or did not express both of them (P =
      0.01738). The Cox proportional hazard regression analysis indicated that iNOS
      expression, vascular invasion, serosal invasion, and microvessel density are
      independent prognostic factors for patients with gastric cancer. CONCLUSIONS:
      iNOS and COX-2 expression of gastric cancer are related to tumor angiogenesis,
      tumor progression, and patient survival in human gastric cancer.

PMID- 16900534
TI  - Surgical outcomes after total mesorectal excision for rectal cancer.
AB  - BACKGROUND AND OBJECTIVES: This study reviewed the results of surgery for distal
      rectal cancer following the introduction of total mesorectal excision (TME) for
      rectal cancer. METHODS: Two hundred sixty-four patients who had undergone
      elective curative surgical resection of rectal cancer within 12 cm of the anal
      verge were included. Comparisons were made between patients who had different
      surgical procedures. RESULTS: The overall operative mortality rate was nil, and
      the morbidity 39.4%. With a mean follow-up of 34 months (range 5-105 months),
      local recurrence occurred in 21 of the patients. The 3- and 5-year actuarial
      local recurrence rates were 9% and 12%, respectively for the whole group.
      Abdominoperineal resection (APR) was necessary in 65 of 264 (24.6%) of the
      patients, with a very low local recurrence rate in this subgroup (5% at 3 years).
      On multivariate analysis, only stage was a significant prognosticator of overall
      survival (P = 0.012). CONCLUSIONS: With the practice of TME, APR was still
      necessary in 25% of patients with rectal cancer within 12 cm of the anal verge.
      Type of surgery and tumor distance from the anal verge influenced local
      recurrence rates, but only initial tumor stage was associated with long-term
      survival.

PMID- 16900536
TI  - The efficacy of breast MRI in predicting breast conservation therapy.
AB  - BACKGROUND: Breast conservation therapy (BCT) has equal efficacy compared to
      mastectomy in treating breast cancer. Accurate pre-operative measurement of tumor
      size can limit re-excision procedures. Breast MRI may improve pre-operative
      evaluation of extent of disease. OBJECTIVE: To examine the correlation of extent
      of disease on breast MRI with pathologic data to determine the utility of breast
      MRI in surgical planning of BCT. METHODS: We retrospectively reviewed our
      prospective database of women undergoing breast MRI. We identified 115 women with
      breast cancer who underwent a breast MRI and a surgical resection from 2000 to
      2003. We compared patients with high-grade tumors (HG, n = 40) to patients with
      low grade (LG, n = 75). RESULTS: The size of the tumor on MRI correlated with the
      pathologic size for HG tumors (HG R = 0.76 vs. LG R = 0.45, P = 0.033).
      Mastectomy was performed in 53 patients. In 10 patients with LG tumors, the MRI
      findings overestimated their disease. In 11 out of 115 patients the primary tumor
      or a second tumor was only seen by MRI. CONCLUSION: Breast MRI does change
      surgical management by detecting additional malignancies. Breast MRI is accurate
      in staging extent of disease in the breast in patients with HG tumors.

PMID- 16900535
TI  - The Kraske procedure: a critical analysis of a surgical approach for mid-rectal
      lesions.
AB  - BACKGROUND AND OBJECTIVES: To analyze the Kraske procedure as an approach to mid
      rectal disease. METHODS: Twenty-two patients underwent a Kraske procedure at
      either Duke University Medical Center, the Durham Veterans Administration Medical
      Center, or the Durham Regional Hospital between 1992 and 1997. The clinical and
      pathologic characteristics of these patients were retrospectively analyzed and
      compared with previous published series. RESULTS: Of the 22 patients, 13
      underwent resection of an adenocarcinoma and 9 underwent resection of a villous
      adenoma. Post-operative complications included four fecal fistulas (two of which
      required a temporary diverting colostomy), two wound infections, two cases of
      urinary retention, and one case of transient fecal incontinence. CONCLUSIONS: The
      Kraske procedure minimizes exposure of mid-rectal lesions without the morbidity
      of a major laparotomy. However, it does carry a moderate complication rate and
      thus should be utilized selectively in managing patients with mid-rectal tumors
      not amenable to other treatment options.

PMID- 16900539
TI  - Frequency response of pig intervertebral disc cells subjected to dynamic
      hydrostatic pressure.
AB  - The pathogenesis of vibration-induced disorders of intervertebral disc at the
      cellular level is largely unknown. Dynamic loads with frequencies close to that
      of the in vivo human spine resonant frequency (4-6 Hz) have a destructive effect,
      which may induce extracellular disc matrix (ECM) degradation. To investigate this
      issue, three-dimensional (3D) alginate cultures of normal pig intervertebral disc
      nucleus and inner annulus cells were tested under dynamic hydrostatic loading.
      Alginate cultures of each region were divided into six groups; five groups were
      exposed to cyclic hydrostatic pressures of frequencies 1, 3, 5, 8, and 10 Hz with
      the same amplitude (1 MPa), and group 6 was the control group (no loading).
      Cultures of different groups were loaded for 3 days (30 min daily) in a hydraulic
      chamber. Effects of loading frequency on disc collagen and protein metabolism
      were investigated by measuring 3H-proline-labeled proteins associated with the
      cells in the extracellular matrix and release of 3H-proline-labeled molecules
      into culture medium. The results indicated a poor synthesis rate and more
      degradation near the 5 Hz frequency. The repeatability of experiments was
      verified by performing two experiments with the same protocol. Both experiments
      indicated that a threshold frequency of around 5 Hz disrupted protein metabolism.

PMID- 16900540
TI  - Contributions of muscles, ligaments, and the ground-reaction force to
      tibiofemoral joint loading during normal gait.
AB  - The aim of this study was twofold: first, to determine which muscles and
      ligaments resist the adduction moment at the knee during normal walking; and
      second, to describe and explain the contributions of muscles, ligaments, and the
      ground reaction force to medial and lateral compartment loading. Muscle forces,
      ground reaction forces, and joint motions obtained from a dynamic optimization
      solution for normal walking were used as input to a three-dimensional model of
      the lower limb. A static equilibrium problem was solved at each instant of the
      gait cycle to determine tibiofemoral joint loading at the knee. Medial
      compartment loading was determined mainly by the orientation of the ground
      reaction force. Because this force vector passed medial to the knee, it applied
      an adduction moment about the joint during stance. In contrast, all of the force
      transmitted by the lateral compartment was due to muscle and ligament action. The
      muscles that contributed most to support and forward propulsion during normal
      walking (quadriceps and gastrocnemius) also contributed most to knee stability in
      the frontal plane. The knee ligaments, particularly those of the posterior
      lateral corner, provided stability to the knee at certain periods of the stance
      phase, when activity of the important stabilizing muscles was low.

PMID- 16900541
TI  - Elastographic imaging of strain distribution in the anterior cruciate ligament
      and at the ligament-bone insertions.
AB  - The anterior cruciate ligament (ACL) functions as a mechanical stabilizer in the
      tibiofemoral joint, and is the most commonly injured knee ligament. To improve
      the clinical outcome of tendon grafts used for ACL reconstructions, our long-term
      goal is to promote graft-bone integration via the regeneration of the native
      ligament-bone interface. An understanding of strain distribution at this
      interface is crucial for functional scaffold design and clinical evaluation.
      Experimental determination, however, has been difficult due to the small length
      scale of the insertion sites. This study utilizes ultrasound elastography to
      characterize the response of the ACL and ACL-bone interface under tension.
      Specifically, bovine tibiofemoral joints were mounted on a material testing
      system and loaded in tension while radiofrequency (RF) data were acquired at 5
      MHz. Axial strain elastograms between RF frames and a reference frame were
      generated using crosscorrelation and recorrelation techniques. Elastographic
      analyses revealed that when the joint was loaded in tension, complex strains with
      both compressive and tensile components occurred at the tibial insertion, with
      higher strains found at the insertion sites. In addition, the displacement was
      greatest at the ACL proper and decreased in value gradually from ligament to
      bone, likely a reflection of the matrix organization at the ligament-bone
      interface. Our results indicate that elastography is a novel method that can be
      readily used to characterize the mechanical properties of the ACL and its
      insertions into bone.

PMID- 16900542
TI  - Side chain mediated electronic contact between a tetrahydro-4H-thiopyran-4
      ylidene-appended polythiophene and CdTe quantum dots.
AB  - The properties of a mixed CdTe quantum dot/tetrahydro-4H-thiopyran-4-ylidene
      functionalized polythiophene system are reported. This system was prepared by
      exposing trioctylphosphine (TOP)-capped CdTe quantum dots to the polythiophene in
      solution. Strong fluorescence emission quenching and shortening of the
      fluorescence emission lifetimes of both the polythiophene and the quantum dots
      occur when they are mixed, indicating the occurrence of photoinduced charge
      separation. Photoinduced absorption spectroscopy reveals a considerable decrease
      in the population of the polythiophene triplet excited state in the mixed system.
      These results demonstrate that between the quantum dots and the polythiophene
      there is both physical and electronic contact, which is mediated by the
      tetrahydro-4H-thiopyran-4-ylidene side chains.

PMID- 16900543
TI  - Quasilinear molecule par excellence, SrCl2: structure from high-temperature gas
      phase electron diffraction and quantum-chemical calculations--computed structures
      of SrCl2.argon complexes.
AB  - The molecular geometry of strontium dichloride has been determined by high
      temperature electron diffraction (ED) and computational techniques. The
      computation at the MP2 level of theory yields a shallow bending potential with a
      barrier of about 0.1 kcal mol(-1) at the linear configuration. The experimentally
      determined thermal average Sr--Cl bond length, r(g), is 2.625+/-0.010 A and the
      bond angle, angle-spherical(a), is 142.4+/-4.0 degrees . There is excellent
      agreement between the equilibrium bond lengths estimated from the experimental
      data, 2.607+/-0.013 A, and computed at different levels of theory and basis sets,
      2.605+/-0.006 A. Based on anharmonic analyses of the symmetric and asymmetric
      stretching as well as the bending motions of the molecule, we estimated the
      thermal average structure from the computation for the temperature of the ED
      experiment. In order to emulate the effect of the matrix environment on the
      measured vibrational frequencies, a series of complexes with argon atoms,
      SrCl(2)Ar(n) (n=1-7), with different geometrical arrangements were calculated.
      The complexes with six or seven argon atoms approximate the interaction best and
      the computed frequencies of these molecules are closer to the experimental ones
      than those computed for the free SrCl(2) molecule.

PMID- 16900544
TI  - MgCl2/R'nAl(OR)3-n: an excellent activator/support for transition-metal complexes
      for olefin polymerization.
AB  - A new and effective method for the activation, and simultaneously, immobilization
      of bis(phenoxyimine) early-transition-metal complexes for olefin polymerization
      (known as FI catalysts), which makes use of MgCl(2)/R'(n)Al(OR)(3-n) as an
      activator/support, has been developed. Ti-, Zr-, and V-FI catalysts combined with
      this MgCl(2)-based compound can form highly active MgCl(2)-supported single-site
      catalysts capable of demonstrating superior catalytic properties, compared to the
      corresponding homogeneous methylaluminoxane- (Ti- and Zr-FI catalysts) or
      alkylaluminum-activation systems (V-FI catalysts), in terms of their catalytic
      activity, molecular weight, stereoselectivity, and comonomer incorporation.
      Additionally, these new catalysts can produce polymers of significant morphology
      with high efficiency. Notably, the MgCl(2)-based compounds can also effectively
      activate and immobilize the early-to-late transition-metal complexes that have
      emerged recently. Thus, the application of MgCl(2)-based compounds as
      activators/supports for transition-metal complexes for olefin polymerization
      provides a conceptually new strategy for the development of methylaluminoxane-
      and borate-free, high-performance, single-site catalysts capable of controlling
      polymer morphology.

PMID- 16900545
TI  - Head-to-head cross-linked adduct between the antitumor unit bis(mu-N,N'-di-p
      tolylformamidinato)dirhodium(II,II) and the DNA fragment d(GpG).
AB  - Reactions of the compound cis-[Rh2(DTolF)2(CH3CN)6](BF4)2, a formamidinate
      derivative of the class of antitumor compounds [Rh2(O2CR)4] (R=Me, Et, Pr), with
      9-ethylguanine (9-EtGuaH) or the dinucleotide d(GpG) proceed by substitution of
      the acetonitrile groups, with the guanine bases spanning the Rh--Rh bond, in a
      bridging fashion, through sites N7/O6. In the case of 9-EtGuaH, both head-to-head
      (HH) and head-to-tail (HT) isomers are formed, whereas with the tethered bases in
      d(GpG), only one right-handed conformer HH1R [Rh2(DTolF)2{d(GpG)}] is present in
      solution. For both cis-[Rh2(DTolF)2(9-EtGuaH)2](BF4)2 and [Rh2(DTolF)2{d(GpG)}],
      the absence of N7 protonation at low pH and the substantial decrease of the pKa
      values for N1-H deprotonation, support N7/O6 binding of the bases to the
      dirhodium core. The N7/O6 binding of the bases is further corroborated by the
      downfield shift by Deltadelta approximately 4.0 ppm of the 13C NMR resonances for
      the C6 nuclei as compared to the corresponding resonances of the free ligands.
      The HH arrangement of the guanine bases in [Rh2(DTolF)2{d(GpG)}] is indicated by
      the intense H8/H8 ROE cross-peaks in the 2D ROESY NMR spectrum. Complete
      characterization of the [Rh2(DTolF)2{d(GpG)}] conformer by 2D NMR spectroscopy
      supports anti-orientation and N (C3'-endo) conformation for both deoxyribose
      residues. The N-pucker for the 5'-G base is universal in such cross-links, but it
      is very unusual for platinum and unprecedented for dirhodium HH cross-linked
      adducts to have both deoxyribose residues in the N-type conformation. The bulk,
      the nonlabile character, and the electron-donating ability of the formamidinate
      bridging groups spanning the dirhodium core affect the nature of the preferred
      dirhodium DNA adducts. Molecular modeling studies performed on
      [Rh2(DTolF)2{d(GpG)}] corroborate the structural features obtained by NMR
      spectroscopy.

PMID- 16900546
TI  - Unique {H(SiR(3))(2)}, (H(2)SiR(3)), H(HSiR(3)), and (H(2))SiR(3) ligand sets
      supported by the {Fe(Cp)(L)} platform (L=CO, PR(3)).
AB  - This work deals with the type and incidence of nonclassical Si--H and H--H
      interactions in a family of silylhydride complexes [Fe(Cp)(OC)(SiMe(n)Cl(3
      n))H(X)] (X=SiMe(n)Cl(3-n), H, Me, n=0-3) and [Fe(Cp)(Me(3)P)(SiMe(n)Cl(3
      n))(2)H] (n=0-3). DFT calculations complemented by atom-in-molecule analysis and
      calculations of NMR hydrogen-silicon coupling constants revealed a surprising
      diversity of nonclassical Si--H and H--H interligand interactions. The compounds
      [Fe(Cp)(L)(SiMe(n)Cl(3-n))(2)H] (L=CO, PMe(3); n=0-3) exhibit an unusual
      distortion from the ideal piano-stool geometry in that the silyl ligands are
      strongly shifted toward the hydride and there is a strong trend towards
      flattening of the {FeSi(2)H} fragment. Such a distortion leads to short Si--H
      contacts (range 2.030-2.075 A) and large Mayer bond orders. A novel feature of
      these extended Si--H interactions is that they are rather insensitive towards the
      substitution at the silicon atom and the orientation of the silyl ligand
      relatively the Fe--H bond. NMR spectroscopy and bonding features of the related
      complexes [Fe(Cp)(OC)(SiMe(n)Cl(3-n))H(Me)] (n=0-3) allow for their
      rationalization as usual eta(2)-Si--H silane sigma-complexes. The series of
      "dihydride" complexes [Fe(Cp)(OC)(SiMe(n)Cl(3-n))H(2)] (n=0-3) is different from
      the previous two families in that the type of interligand interactions strongly
      depends on the substitution on silicon. They can be classified either as usual
      dihydrogen complexes, for example, [Fe(Cp)(OC)(SiMe(2)Cl)(eta(2)-H(2))], or as
      compounds with nonclassical H--Si interactions, for example,
      [Fe(Cp)(OC)(H)(2)(SiMe(3))] (16). These nonclassical interligand interactions are
      characterized by increased negative J(H,Si) (e.g. -27.5 Hz) and increased J(H,H)
      (e.g. 67.7 Hz).

PMID- 16900547
TI  - Biosynthetic inorganic chemistry.
AB  - Inorganic chemistry and biology can benefit greatly from each other. Although
      synthetic and physical inorganic chemistry have been greatly successful in
      clarifying the role of metal ions in biological systems, the time may now be
      right to utilize biological systems to advance coordination chemistry. One such
      example is the use of small, stable, easy-to-make, and well-characterized
      proteins as ligands to synthesize novel inorganic compounds. This biosynthetic
      inorganic chemistry is possible thanks to a number of developments in biology.
      This review summarizes the progress in the synthesis of close models of complex
      metalloproteins, followed by a description of recent advances in using the
      approach for making novel compounds that are unprecedented in either inorganic
      chemistry or biology. The focus is mainly on synthetic "tricks" learned from
      biology, as well as novel structures and insights obtained. The advantages and
      disadvantages of this biosynthetic approach are discussed.

PMID- 16900548
TI  - Efficient synthesis of functionalized organozinc compounds by the direct
      insertion of zinc into organic iodides and bromides.

PMID- 16900550
TI  - Gold(I)-catalyzed intermolecular cyclopropanation of enynes with alkenes:
      trapping of two different gold carbenes.

PMID- 16900549
TI  - Luminescence studies of the intracellular distribution of a dinuclear gold(I) N
      heterocyclic carbene complex.

PMID- 16900553
TI  - Performance of adaptive sample size adjustment with respect to stopping criteria
      and time of interim analysis.
AB  - The benefit of adjusting the sample size in clinical trials on the basis of
      treatment effects observed in interim analysis has been the subject of several
      recent papers. Different conclusions were drawn about the usefulness of this
      approach for gaining power or saving sample size, because of differences in trial
      design and setting. We examined the benefit of sample size adjustment in relation
      to trial design parameters such as 'time of interim analysis' and 'choice of
      stopping criteria'. We compared the adaptive weighted inverse normal method with
      classical group sequential methods for the most common and for optimal stopping
      criteria in early, half-time and late interim analyses. We found that reacting to
      interim data might significantly reduce average sample size in some situations,
      while classical approaches can out-perform the adaptive designs under other
      circumstances. We characterized these situations with respect to time of interim
      analysis and choice of stopping criteria.

PMID- 16900551
TI  - A sequential procedure for monitoring clinical trials against historical
      controls.
AB  - In this paper, we develop a sequential procedure to monitor clinical trials
      against historical controls. When there is a strong ethical concern about
      randomizing patients to existing treatment because biological and medical
      evidence suggests that the new treatment is potentially superior to the existing
      one, or when the enrollment is too limited for randomization of subjects into
      experimental and control groups, one can monitor the trial sequentially against
      historical controls if the historical data with required quality and sample size
      are available to form a valid reference for the trial. This design of trial is
      sometimes the only alternative to a randomized phase III trial design that is
      intended but not feasible in situations such as above. Monitoring this type of
      clinical trial leads to a statistical problem of comparing two population means
      in a situation in which data from one population are sequentially collected and
      compared with all data from the other population at each interim look. The
      proposed sequential procedures is based on the sequential conditional probability
      ratio test (SCPRT) by which the conclusion of the sequential test would be
      virtually the same as that arrived at by a non-sequential test based on all data
      at the planned end of the trial. We develop the sequential procedure by proposing
      a Brownian motion that emulates the test statistic, and then proposing an SCPRT
      that is adapted to the special properties of the trial.

PMID- 16900555
TI  - Effectiveness of tibolone on the reduction of menopausal problems--a Bayesian
      semi-parametric interpretation.
AB  - Two major physiological problems women experience at the time of menopause are
      hot flush and vaginal dryness. Exploratory investigations reveal that these two
      binary outcomes are very much dependent as both of them have predominant
      oestrogenic effects. A primary interest is to investigate how the bivariate
      association and the marginal univariate risks are affected by repeated
      measurements on each woman over several months. To achieve this we propose a very
      general class of bivariate binary models. Parametric inference is drawn on the
      basis of full non-parametric Bayesian approach under Dirichlet process mixture.
      Study addresses some more interesting phenomena on the effectiveness of tibolone
      treatment in reducing menopausal problems. A simulation study further strengthens
      the proposed methodology.

PMID- 16900556
TI  - Comparing the small sample performance of several variance estimators under
      competing risks.
AB  - We examine several variance estimators for cumulative incidence estimators that
      have been proposed over time, some of which are derived from asymptotic
      martingale or counting process theory, and some of which are developed from the
      moments of the multinomial distribution. There is little published work comparing
      these variance estimators, largely because the variance estimators are
      algebraically complex and difficult to interpret and all but one have yet to be
      programmed for a standard statistical package. Through simulation and application
      to real data, we compare the performance of six variance estimators in relation
      to each other and the bootstrap in order to confirm earlier reports of their
      performance and to provide future direction toward their application. We find
      that the multinomial-moment-based estimators have performance close to that of
      the bootstrap, and are quite accurate for estimating the variance, even in
      samples of 20 subjects. All but one of the martingale theory-based estimators
      tend to perform poorly in small samples, tending to either overestimate or
      underestimate the empirical variance in samples of fewer than 100 subjects.

PMID- 16900557
TI  - Using mixed treatment comparisons and meta-regression to perform indirect
      comparisons to estimate the efficacy of biologic treatments in rheumatoid
      arthritis.
AB  - Mixed treatment comparison (MTC) is a generalization of meta-analysis. Instead of
      the same treatment for a disease being tested in a number of studies, a number of
      different interventions are considered. Meta-regression is also a generalization
      of meta-analysis where an attempt is made to explain the heterogeneity between
      the treatment effects in the studies by regressing on study-level covariables.
      Our focus is where there are several different treatments considered in a number
      of randomized controlled trials in a specific disease, the same treatment can be
      applied in several arms within a study, and where differences in efficacy can be
      explained by differences in the study settings. We develop methods for
      simultaneously comparing several treatments and adjusting for study-level
      covariables by combining ideas from MTC and meta-regression. We use a case study
      from rheumatoid arthritis. We identified relevant trials of biologic verses
      standard therapy or placebo and extracted the doses, comparators and patient
      baseline characteristics. Efficacy is measured using the log odds ratio of
      achieving six-month ACR50 responder status. A random-effects meta-regression
      model is fitted which adjusts the log odds ratio for study-level prognostic
      factors. A different random-effect distribution on the log odds ratios is allowed
      for each different treatment. The odds ratio is found as a function of the
      prognostic factors for each treatment. The apparent differences in the randomized
      trials between tumour necrosis factor alpha (TNF- alpha) antagonists are
      explained by differences in prognostic factors and the analysis suggests that
      these drugs as a class are not different from each other.

PMID- 16900558
TI  - A survivin-mediated oncolytic adenovirus induces non-apoptotic cell death in lung
      cancer cells and shows antitumoral potential in vivo.
AB  - BACKGROUND: Conditionally replicating adenoviruses or oncolytic adenoviruses,
      which can replicate selectively in tumor cells and kill them, represent an
      innovative class of promising cancer therapeutics. Survivin is the smallest
      member of the inhibitor of apoptosis (IAP) family, which is transcriptionally
      upregulated exclusively in most malignant tissues but not in normal tissues. It
      has been reported that activity of the survivin promoter is tumor-specific, which
      makes the survivin promoter a good candidate to construct oncolytic viral
      vectors. METHODS: A luciferase reporter assay was used to determine the activity
      of the survivin promoter in tumor and normal cells. An oncolytic adenovirus
      (Ad.SP/E1A) was generated by homologous recombination. The oncolytic efficacy of
      Ad.SP/E1A was evaluated in cell lines and in a human lung xenograft tumor mouse
      model. RESULTS: Survivin expression was highly upregulated in tumor cells both at
      the protein and mRNA level. The luciferase reporter assay showed that survivin
      promoter activity is tumor-specific. Ad.SP/E1A expressed E1A selectively in tumor
      cells and induced cytotoxicity, but not in normal cells. Moreover, in animal
      experiments, intratumoral administration of Ad.SP/E1A significantly suppressed
      the growth of xenograft tumors. Further investigation showed that Ad.SP/E1A
      induced cell death by an apoptosis-independent pathway. CONCLUSIONS: Ad.SP/E1A
      could be a potent therapeutic agent for cancer gene therapy. The investigation of
      the mechanisms of oncolytic virus-induced cell death in this work will shed light
      on the construction of more powerful vectors for cancer therapy.

PMID- 16900559
TI  - On estimating treatment effects under non-compliance in randomized clinical
      trials: are intent-to-treat or instrumental variables analyses perfect solutions?
AB  - In this report, we compared four estimators (intent-to-treat, as treated, per
      protocol, and instrumental variables estimators) that are conventionally
      considered for treatment effect estimation by simulation under different non
      compliance scenarios in typical clinical trial settings. We found that intent-to
      treat and instrumental variables estimators are not perfect and can be
      problematic in some situations although these two estimators carry desirable
      properties as we assume.

PMID- 16900560
TI  - Stochastically curtailed phase II clinical trials.
AB  - Phase II trials often test the null hypothesis H(0): p <or= p(0) versus H(1): p
      >or=p(1), where p is the true unknown proportion responding to the new treatment,
      p(0) is the greatest response proportion which is deemed clinically ineffective,
      and p(1) is the smallest response proportion which is deemed clinically
      effective. In order to expose the fewest number of patients to an ineffective
      therapy, phase II clinical trials should terminate early when the trial fails to
      produce sufficient evidence of therapeutic activity (i.e. if p <or=p(0)).
      Simultaneously, if a treatment is highly effective (i.e. if p>or=p(1)), the trial
      should declare the drug effective in the fewest patients possible to allow for
      advancement to a phase III comparative trial. Several statistical designs,
      including Simon's minimax and optimal designs, have been developed that meet
      these requirements. In this paper, we propose three alternative designs that rely
      upon stochastic curtailment based on conditional power. We compare and contrast
      the properties of the three approaches: (1) stochastically curtailed (SC)
      binomial tests, (2) stochastically curtailed (SC) Simon's optimal design, and (3)
      SC Simon's minimax design to those of Simon's minimax and Simon's optimal
      designs. For each of these designs we compare and contrast the number of
      opportunities for study termination, the expected sample size of the trial under
      the null hypothesis (p <or=p(0)), and the effective type I and type II errors. We
      also present graphical tools for monitoring phase II clinical trials with
      stochastic curtailment using conditional power.

PMID- 16900561
TI  - Induction of splice correction by cell-penetrating peptide nucleic acids.
AB  - BACKGROUND: Directing splicing using oligonucleotides constitutes a promising
      therapeutic tool for a variety of diseases such as beta-thalassemia, cystic
      fibrosis, and certain cancers. The rationale is to block aberrant splice sites,
      thus directing the splicing of the pre-mRNA towards the desired protein product.
      One of the difficulties in this setup is the poor bioavailability of
      oligonucleotides, as the most frequently used transfection agents are unsuitable
      for in vivo use. Here we present splice-correcting peptide nucleic acids (PNAs),
      tethered to a variety of cell-penetrating peptides (CPPs), evaluating their
      mechanism of uptake and ability to correct aberrant splicing. METHODS: HeLa cells
      stably expressing luciferase containing an aberrant splice site were used. A
      previously described PNA sequence, capable of correcting the aberrant splicing,
      was conjugated to the CPPs, Tat, penetratin and transportan, via a disulfide
      bridge. The ability of the CPP-PNA conjugates to correct splicing was measured,
      and membrane disturbance and cell viability were evaluated using LDH leakage and
      WST-1 assays. Lysosomotropic agents, inhibition of endocytosis at 4 degrees C and
      confocal microscopy were used to investigate the importance of endocytosis in the
      uptake of the cell-penetrating PNAs. RESULTS: All the three CPPs were able to
      promote PNA translocation across the plasma membrane and induce splice
      correction. Transportan (TP) was the most potent vector and significantly
      restored splicing in a concentration-dependent manner. Interestingly, TP also
      rendered a concentration-dependent splice correction in serum, in contrast to Tat
      and penetratin. Addition of the lysosomotrophic agent chloroquine increases the
      splice correction efficacy of the CPP-PNA conjugates up to 4-fold, which together
      with experiments at 4 degrees C and the visual information from confocal
      microscopy, indicate that the mechanism of uptake responsible for internalization
      of CPP-PNA conjugates is mainly endocytic. Finally, co-localization studies with
      dextran further indicate that conjugates, at least in the case of TP, internalize
      via endocytosis and in particular macropinocytosis. CONCLUSIONS: These data
      demonstrate that CPPs can be used for the delivery of splice-correcting PNAs,
      with potential to be used as a therapeutic approach for regulating splicing in a
      variety of diseases. Transportan presents itself as the overall most suitable
      vector in this study, generating the most efficient conjugates for splice
      correction.

PMID- 16900562
TI  - Characterization of O2-CeO2 interactions using in situ Raman spectroscopy and
      first-principle calculations.
AB  - Interactions between O(2) and CeO(2) are examined experimentally using in situ
      Raman spectroscopy and theoretically using density-functional slab-model
      calculations. Two distinct oxygen bands appear at 825 and 1131 cm(-1),
      corresponding to peroxo- and superoxo-like species, respectively, when partially
      reduced CeO(2) is exposed to 10 % O(2). Periodic density-functional theory (DFT)
      calculations aid the interpretation of spectroscopic observations and provide
      energetic and geometric information for the dioxygen species adsorbed on CeO(2).
      The O(2) adsorption energies on unreduced CeO(2) surfaces are endothermic
      (0.91<DeltaE(ads)<0.98 eV), while those on reduced surfaces are exothermic (-4.
      0<DeltaE(ads)<-0.9 eV), depending on other relevant surface processes such as
      chemisorption and diffusion into the bulk. Partial reduction of surface Ce(4+) to
      Ce(3+) (together with formation of oxygen vacancies) alters geometrical
      parameters and, accordingly, leads to a shift in the vibrational frequencies of
      adsorbed oxygen species compared to those on unreduced CeO(2). Moreover, the
      location of oxygen vacancies affects the formation and subsequent dissociation of
      oxygen species on the surfaces. DFT predictions of the energetics support the
      experimental observation that the reduced surfaces are energetically more
      favorable than the unreduced surfaces for oxygen adsorption and reduction.

PMID- 16900563
TI  - A photophysical study of terphenyl core oligosulfonimide dendrimers exhibiting
      high steady-state anisotropy.
AB  - The photophysical properties of three dendrimers containing a p-terphenyl core
      with appended sulfonimide branches of different size and n-octyl chains have been
      investigated in dichloromethane solution. In the dendrimer absorption spectra
      contributions from both the branches and the core are clearly identified. The
      fluorescence spectra show only the characteristic fluorescence of the terphenyl
      unit. Energy transfer from the appended chromophoric groups to the core does not
      occur. In the dendrimers, the terphenyl core exhibits a very high fluorescence
      quantum yield (ca. 0.75) and a short emission lifetime (0.8 ns). These properties
      allowed investigations of the fluorescence depolarization caused by rotation of
      the dendrimers. The dendrimers show a very high steady-state anisotropy in
      dichloromethane solution at room temperature (0.24 for the largest one), compared
      to that of the parent terphenyl under the same experimental conditions (<0.01)
      and in rigid matrix (0.33). Both the n-octyl chains and the sulfonimide branches
      play important roles to slow down the molecular rotation.

PMID- 16900564
TI  - An autoregressive linear mixed effects model for the analysis of longitudinal
      data which show profiles approaching asymptotes.
AB  - In longitudinal data, a continuous response sometimes shows a profile approaching
      an asymptote. For such data, we propose a new class of models, autoregressive
      linear mixed effects models in which the current response is regressed on the
      previous response, fixed effects, and random effects. Asymptotes can shift
      depending on treatment groups, individuals, and so on, and can be modelled by
      fixed and random effects. We also propose error structures that are useful in
      practice. The estimation methods of linear mixed effects models can be used as
      long as there is no intermittent missing.

PMID- 16900565
TI  - Complete 1H, 13C and 15N NMR assignment of tirapazamine and related 1,2,4
      benzotriazine N-oxides.
AB  - 1H, 13C and 15N NMR measurements (1D and 2D including 1H--15N gs-HMBC) have been
      carried out on 3-amino-1, 2,4-benzotriazine and a series of N-oxides and complete
      assignments established. N-Oxidation at any position resulted in large upfield
      shifts of the corresponding N-1 and N-2 resonances and downfield shifts for N-4
      with the exception of the 3-amino-1,2,4-benzotriazine 1-oxide in which a small
      upfield shift of N-4 was observed. Density functional GIAO calculations of the
      15N and 13C chemical shifts [B3LYP/6-31G(d)//B3LYP/6-311+G(2d,p)] gave good
      agreement with experimental values confirming the assignments. The combination of
      13C and 15N NMR provides an unambiguous method for assigning the 1H and 13C
      resonances of N-oxides of 1,2,4-benzotriazines.

PMID- 16900566
TI  - An introductory note to the CHMP guidelines: choice of the non-inferiority margin
      and data monitoring committees by David Brown, Peter Volkers and Simon Day,
      Statistics in Medicine 2006; 25:1623-1627.

PMID- 16900567
TI  - Instrumental variables and interactions in the causal analysis of a complex
      clinical trial.
AB  - We consider the application of instrumental variable techniques in a longitudinal
      clinical trial in paediatric HIV/AIDS, with a substantial degree of non
      compliance to randomized treatment (Nelfinavir versus placebo) and with left
      censoring of the outcome variable (HIV RNA concentration). We consider in detail
      the assumptions and implications behind the inclusion and exclusion of
      interactions between randomized arm and baseline covariates in modelling actual
      treatment received, and between treatment and baseline covariates in modelling
      outcome. Estimated treatment effects were sensitive to inclusion of interactions,
      and we show how such sensitivity can be explored and explained.

PMID- 16900568
TI  - A nonlinear latent class model for joint analysis of multivariate longitudinal
      data and a binary outcome.
AB  - We consider a joint model for exploring association between several correlated
      longitudinal markers and a clinical event. A nonlinear growth mixture model
      exhibits the different latent classes of evolution of the latent quantity
      underlying the correlated longitudinal markers and a logistic regression models
      the probability of occurence of the clinical event according to the latent
      classes. By introducing a flexible nonlinear transformation including parameters
      to be estimated between each marker and the latent process, the model also deals
      with non-Gaussian continuous markers. Through an application on cognitive ageing,
      the two advantages of the model are underlined: (1) the latent profiles of
      evolution associated with the clinical event are described including covariate
      effects in the longitudinal model but also in the probability of class membership
      and in the probability of occurence of the event, and (2) a diagnostic and a
      prognostic tools are derived from the model for early detection of the clinical
      event using any available information about the longitudinal markers.

PMID- 16900570
TI  - An overall strategy based on regression models to estimate relative survival and
      model the effects of prognostic factors in cancer survival studies.
AB  - Relative survival provides a measure of the proportion of patients dying from the
      disease under study without requiring the knowledge of the cause of death. We
      propose an overall strategy based on regression models to estimate the relative
      survival and model the effects of potential prognostic factors. The baseline
      hazard was modelled until 10 years follow-up using parametric continuous
      functions. Six models including cubic regression splines were considered and the
      Akaike Information Criterion was used to select the final model. This approach
      yielded smooth and reliable estimates of mortality hazard and allowed us to deal
      with sparse data taking into account all the available information. Splines were
      also used to model simultaneously non-linear effects of continuous covariates and
      time-dependent hazard ratios. This led to a graphical representation of the
      hazard ratio that can be useful for clinical interpretation. Estimates of these
      models were obtained by likelihood maximization. We showed that these estimates
      could be also obtained using standard algorithms for Poisson regression.

PMID- 16900572
TI  - NMR study on the structure and stability of 4-substituted aromatic iodosyl
      compounds.
AB  - Two 4-substituted aromatic iodosyl compounds were investigated with regard to
      their solubility, stability and chromatographic behaviour. 1-Iodosyl-4-methoxy-
      and 1-iodosyl-4-nitro-benzene are soluble in methanol and provide acceptable 1H
      and 13C NMR spectra; however, gradual oxidation of the solvent was observed. LC
      MS analyses suggest that unlike the parent substance, iodosylbenzene, which has a
      polymeric structure, both compounds rather exist in the monomeric form.

PMID- 16900573
TI  - A two-stage sample size recalculation procedure for placebo- and active
      controlled non-inferiority trials.
AB  - Many non-inferiority trials of a test treatment versus an active control may
      also, if ethical, incorporate a placebo arm. Inclusion of a placebo arm enables a
      direct assessment of assay sensitivity. It also allows construction of a non
      inferiority test that avoids the problematic specification of an absolute non
      inferiority margin, and instead evaluates whether the test treatment preserves a
      pre-specified proportion of the effect of the active control over placebo. We
      describe a two-stage procedure for sample size recalculation in such a setting
      that maintains the desired power more closely than a fixed sample approach when
      the magnitude of the effect of the active control differs from that anticipated.
      We derive an allocation rule for randomization under which the procedure
      preserves the type I error rate, and show that this coincides with that
      previously presented for optimal allocation of the sample size among the three
      treatment arms.

PMID- 16900575
TI  - Analysing and interpreting competing risk data.
AB  - When competing risks are present, two types of analysis can be performed:
      modelling the cause specific hazard and modelling the hazard of the
      subdistribution. This paper contrasts these two methods and presents the benefits
      of each. The interpretation is specific to the analysis performed. When modelling
      the cause specific hazard, one performs the analysis under the assumption that
      the competing risks do not exist. This could be beneficial when, for example, the
      main interest is whether the treatment works in general. In modelling the hazard
      of the subdistribution, one incorporates the competing risks in the analysis.
      This analysis compares the observed incidence of the event of interest between
      groups. The latter analysis is specific to the structure of the observed data and
      it can be generalized only to another population with similar competing risks.

PMID- 16900576
TI  - Advances in statistical human genetics over the last 25 years.
AB  - The past 25 years has seen an explosion in the number of genetic markers that can
      be measured on DNA samples at an ever decreasing cost. Although basic statistical
      methods for analysing such data gathered on samples of either independent
      individuals or family members, one or two markers at a time, were already well
      developed before this explosion occurred, there has been a corresponding burst in
      activity to develop multiple marker models to find disease-causing gene variants,
      capitalizing on the data that have become available, to increase the power of
      such methods. This has required the concomitant development of faster algorithms
      to speed up the computation of various likelihoods. For linkage analysis, to
      obtain the approximate locations for genes of interest, Mendelian segregation
      models have been extended to be more realistic and statistical models that do not
      assume specific modes of inheritance have been extended to allow for the analysis
      of larger pedigree structures. For association analysis, to obtain more precise
      locations for genes of interest, the recent completion of the first stage of the
      HapMap project has spurred the development, still underway, of novel experimental
      designs and analytical methods to combat the curse of dimensionality and the
      resulting multiple testing problem. Perhaps the greatest current challenge
      concerns how best to gather and synthesize the many lines of evidence possible in
      order to discover the genetic determinants underlying complex diseases.

PMID- 16900577
TI  - Effects of lambda-cyhalothrin on mosquito larvae and predatory aquatic insects.
AB  - Agricultural insecticides can affect mosquito production in rice fields by
      controlling mosquitoes, disrupting biological control or contributing to
      selection of insecticide resistance. The duration of insecticidal activity of the
      pyrethroid lambda-cyhalothrin was quantified on predatory insects in rice fields
      and on three kinds of mosquito larva: a pyrethroid-susceptible strain of Culex
      tarsalis Coquillet, a pyrethroid-resistant strain of Cx pipiens L. (sensu lato)
      and non-resistant Cx pipiens s.l. Lambda-cyhalothrin killed most caged,
      susceptible mosquitoes for up to 21 days. It killed fewer resistant Cx pipiens
      s.l., but suppressed their survival for over a week. Lambda-cyhalothrin
      suppressed field populations of predatory insects through day 29. Agricultural
      use of lambda-cyhalothrin can provide incidental mosquito control. However, the
      pyrethroid persisted in sediment and gradually decreased in activity, which could
      contribute to selection of pyrethroid-resistant mosquitoes. Because caged
      mosquitoes showed good survival before predators recovered, disruption of
      biological control is possible. It is therefore advisable for growers and
      mosquito control agencies to communicate about pesticide use.

PMID- 16900578
TI  - Molecular characterization of the two-component histidine kinase gene from
      Monilinia fructicola.
AB  - Brown rot of stone fruit caused by Monilinia fructicola (G. Wint) Honey is one of
      the most common fungal diseases in California. In this study, two laboratory
      induced iprodione-resistant (LIR) mutants of M. fructicola were characterized by
      osmotic sensitivity, virulence on prune and sequence of the two-component
      histidine kinase gene (Mfos-1). The LIR mutants showed more sensitivity to
      osmotic stress and lower virulence on prune than their wild-type parent. Analysis
      of deduced amino acid of Mfos-1 showed that this protein exhibited all the
      characteristic features of the two-component histidine kinase genes, including
      osmotic sensing domain, six 90-amino-acid repeat motifs (coiled coil region) and
      kinase core and response regulator domains. Comparison of DNA sequences of the
      Mfos-1 from LIR mutants and the wild-type sensitive (S) isolate showed that LIR
      mutants had single point mutations in the coiled coil region of Mfos-1.

PMID- 16900579
TI  - An in vitro screening assay to discover novel inhibitors of 4-coumarate:CoA
      ligase.
AB  - 4-Coumarate:CoA ligase (4CL, EC 6.2.1.12) exists only in plants and plays an
      important role in the phenylpropanoid pathway. Identification of inhibitors
      targeting 4CL provides a novel approach for developing effective plant growth
      inhibitors (PGIs). The full-length gene of tobacco 4CL (Nt4CL1) was cloned and
      expressed in Escherichia coli Cast & Chalm. The recombinant 4CL protein was
      extracted and purified by several purification steps including gel-filtration and
      anion-exchange chromatography. 4CL activity assay was miniaturized and optimized
      using a 96-well microplate and a reader. Among 28 existing herbicides, propanil
      and swep strongly inhibited in vitro 4CL enzyme activity, and they were selected
      for further studies. The process of this assay can be developed into a high
      throughput screening system of PGI targeting 4CL in the phenylpropanoid pathway.

PMID- 16900580
TI  - Physicians' real income continues to fall.

PMID- 16900582
TI  - Scully settlement draws ire.

PMID- 16900581
TI  - The ordeal of practicing care.

PMID- 16900583
TI  - [The center for psychosocial attention's tutorship residence project: from a
      clinical question to another].
AB  - This paper studied the Projeto Moradia (Tutorship Residence Project) as a
      clinical instrument, adopting a psychoanalytical reference, based on a clinical
      case study. The objective was to analyze if the project's interventions enables
      the patient to become stable by constructing a delirious metaphor. The results
      showed the impact of the project on the life of residents: being accepted, thus
      demonstrating the successful attainment of its objectives with respect to
      autonomy, reduced social isolation and intervention in problematic housing
      questions, articulating "two clinics": one that interferes directly in the
      resident's life through project interventions, and the other, which supports it,
      but operates in other instances of treatment, creating a relationship of
      institutional interdependency.

PMID- 16900584
TI  - [Hyperferritinemia-cataract syndrome associated to the HFE gene mutation. Two new
      Spanish families and a new mutation (A37T: "Zaragoza")].
AB  - BACKGROUND AND OBJECTIVE: Nuclear congenital cataracts associated with
      hyperferritinemia--hereditary hyperferritinemia cataract syndrome (HHCS)--without
      clinical or biochemical signs of iron overload have been recently described in
      several Spanish families. This HHCS is associated with mutations in the gene of
      ferritin subunit L, located in chromosome 19. We describe 2 new families with
      HHCS, one of them presenting a new L-ferritin mutation (A37T: -Zaragoza-).
      PATIENTS AND METHOD: Patients and probands were studied according to the Anemia
      Unit protocol: complete blood count, biochemical profile (diabetes, hepatic and
      renal), hepatic serologies, iron metabolism (iron, transferrin, ferritin,
      transferrin saturation, reactive C protein) and mutation HFE gene studies (C282Y,
      H63D). All of them were sent to the Ophthalmology Service for cataract study. L
      ferritin mutational scanning was performed by denaturing high performance liquid
      chromatography (DHPLC). Samples displaying an altered elution profile, as
      compared to a wild type control, were directly sequenced for the precise
      characterization of the L-ferritin mutation. RESULTS: Family A proband was a 54
      year-old-female, with cataracts, ferritin level: 942 pg/I, transferrin
      saturation: 14%, HFE gen study: H63D/H63D; L-ferritin gene study: C33T mutation/
      . Her two sons had cataracts, hyperferritinemia (1607, and 1188 pg/I,
      respectively), normal transferrin saturation (40% and 9%), HFE gene study:
      H63D/N; and L-ferritin gen study: C33T/-. Family B proband was a 39 year-old
      female, with cataract, ferritin level: 636 pg/I, transferrin saturation: 25%, HFE
      gene study: H63D/N; and L-ferritin gene study: A37T/-. Her two sons, sister,
      brother and nephew, who were affected with A37T mutation, showed
      hyperferritinemia (883, 747, 835, 613 and 1396 pg/I) with normal transferrin
      saturation levels (17%, 34%, 25%, 18% and 24%); but the ferritin levels of those
      non-affected were normal (35 and 50 pg/I). CONCLUSIONS: HHCS is a dominant
      autosomic condition, with a possible world-wide distribution,which should be
      included in the differential diagnosis of hyperferritinemia studies. It is
      important to suspect it in order to avoid wrong treatment.

PMID- 16900585
TI  - Proteomics: perspectives for biomedical research. Proceedings of a meeting,
      February 4, 2005, Rome, Italy.

PMID- 16900586
TI  - Bibliography. Current world literature. Reproductive endocrinology.

PMID- 16900587
TI  - Radiographic progression in ankylosing spondylitis patients treated with
      infliximab.

PMID- 16900588
TI  - Corticosteroids to treat fever in IVIG-refractory KD.

PMID- 16900589
TI  - The inclusion of corticosteroids in treatment regimens for Kawasaki disease:
      effect on coronary aneurysms.

PMID- 16900590
TI  - Bibliography. Current world literature. Anaesthesia outside the operating room.

PMID- 16900591
TI  - [Hypersensitivity syndrome to phenitoin].

PMID- 16900592
TI  - [Celiac disease in adult patients. A different clinical spectre].

PMID- 16900593
TI  - Abstracts of the XXXVII Nordic Meeting of Gastroenterology, 3-5 May 2006,
      Vasteras, Sweden.

PMID- 16900594
TI  - [Toxic like syndrome as presentation of lung abscess due to Streptococcus
      pneumoniae].

PMID- 16900595
TI  - [Breast metastases of gastric carcinoma mimicking inflammatory carcinoma].

PMID- 16900596
TI  - Tyrosine kinase inhibitors: the next generation.

PMID- 16900597
TI  - G-CSF could worsen anaemia in breast cancer.

PMID- 16900598
TI  - Haemoglobin and breast-cancer response.

PMID- 16900599
TI  - Predictive model for hereditary colorectal cancer.

PMID- 16900600
TI  - [Retroperitoneal hematoma with femoral neuropathy, conservative or surgical
      approach?].

PMID- 16900601
TI  - Primary excision benefit for metastatic breast cancer.

PMID- 16900602
TI  - Patients' genotype could reduce effectiveness of tamoxifen.

PMID- 16900603
TI  - Accommodative intraocular lenses for age-related cataracts.
AB  - The standard intraocular lens (IOL) that is used to replace a cataractous lens
      cannot change focus from distant to near objects, so most patients need glasses
      for near vision after cataract surgery. Limited evidence suggests that
      accommodative IOLs provide better near vision than monofocal IOLs, but not better
      than multifocal IOLs. Long-term follow-up is needed to confirm patient outcomes,
      and determine whether the benefits justify the additional cost.

PMID- 16900604
TI  - Ten Years of ECOS International, 19-21 August 2004, Mexico City, Mexico.

PMID- 16900605
TI  - [Diagnostic difficulty and Medicine Based on Evidence].

PMID- 16900606
TI  - Carcinogenicity of nitrate, nitrite, and cyanobacterial peptide toxins.

PMID- 16900607
TI  - Protozoal reproduction losses in farm ruminants. Neospora and neosporosis:
      achievements and perspectives. Abstracts of meetings September 2005, Poland.

PMID- 16900608
TI  - International Society for Cellular Therapy Annual Meeting, Berlin, Germany, 2006.
      Abstracts.

PMID- 16900609
TI  - A comparative efficacy and safety study of long-acting risperidone injection and
      risperidone oral tablets among hospitalized patients: 12-week randomized, single
      blind study.
AB  - OBJECTIVE: The superiority of risperidone long-acting injection (RLAI) over oral
      typical and atypical antipsychotics demonstrated in previous studies may be
      related to the improved drug compliance. The aim of the 12-week randomized,
      single-blind study was to test whether the superiority of RLAI remained among
      hospitalized patients that drug compliance could be optimally controlled.
      METHODS: Fifty hospitalized stable schizophrenic patients, who had maintained on
      oral risperidone for more than 3 months, were randomized to the RLAI and oral
      risperidone group. Finally 49 patients (98 %) completed the study, and no dose
      change of oral risperidone, or RLAI was noted among all patients. RESULTS: The
      RLAI group showed significantly increased positive score of Positive and Negative
      Syndrome Scale (PANSS) than the risperidone group (0.72 +/- 3.52 vs. -1.24 +/-
      3.81, p = 0.022), but without significance difference for the PANSS total,
      negative and general psychopathology scores. The RLAI group also showed a
      significantly improved Udvalg for Kliniske Undersogelser (UKU) Scale (p = 0.037),
      social life domains of Short-Form Health Survey (SF-36) (p = 0.011), and reduced
      prolactin level (p = 0.001). CONCLUSION: The results indicated that with optimal
      controlling of drug compliance among hospitalized patients, RLAI showed no
      benefit of efficacy over oral risperidone, but with advantages of improved side
      effect profiles, social life ratings, and reduced prolactin levels.

PMID- 16900610
TI  - The CARI guidelines. Haematological targets. Iron.

PMID- 16900611
TI  - Refusal to consent to treatment on religious grounds.

PMID- 16900612
TI  - The "Seymour Report" on Fetal Welfare and the Law in Australia.

PMID- 16900613
TI  - The regulation of in-vitro fertilisation: social norms and discrimination.

PMID- 16900614
TI  - A cross sectional study of hepatitis B, C, some trace elements, heavy metals,
      aflatoxin B1 and schistosomiasis in a rural population, Egypt.
AB  - Chronic liver diseases are disastrous to health. Many factors are associated with
      their prevalence, hence endemicity. These are mainly infectious, parasitic and
      toxic. A survey was conducted in a village south to Cairo. Large industries
      concerned with iron and steel industry, metals smelting, cement manufacturing and
      electric station were located north to the village. A systematic random sample of
      houses was selected. All individuals inside the houses were invited to share in
      the study. Sample size was 84 individuals. Hepatitis markers were done (HBsAg and
      anti-HCV antibodies). The levels of some heavy metals were assessed; which were
      lead, mercury, arsenic, aluminum, manganese, nickel, chromium and cadmium. Levels
      of some trace elements were assessed. These were copper, iron, selenium and zinc.
      Aflatoxin B1 was assessed in serum. Assessment of schistosomal circulating
      antigen and antibodies was carried out. Abdominal ultrasonograghy was done to
      assess liver condition. Univariate logistic regression analysis was done to
      assess the association between studied variables and HBsAg or anti-HCV sero
      positive subjects. The association between studied variables and bilharzial or
      fatty liver, diagnosed by ultrasonography, were also assessed. The univariate
      logistic regression analysis revealed odds ratios at the following results. For
      HBsAg seropositive subjects, aflatoxin B1, lead, chromium and schistosomal
      antigen and antibodies were higher than negative ones where odds ratios were;
      6.2, 1.6, 1.6, 1.6 and 1.7, respectively. None of the variables showed
      statistically significant difference. For anti-HCV antibodies sero-positive
      subjects, aflatoxin B1 and chromium had the highest odds ratios among the studied
      variables, (odds ratios were 2.5 and 2.4, respectively). Bilharzial liver showed
      higher significant positivity of anti-HCV antibodies and insignificant decreased
      level of zinc than negative ones (odds ratios were 7.2 and 4.5, respectively).
      Fatty liver cases showed higher statistically significant positivity of anti-HCV
      antibodies and chromium than negative ones. Odds ratios were 8.0 and 7.1,
      respectively. Statistically significant lower level of aflatoxin B1 was shown in
      fatty liver than normal liver subjects. Multivariate logistic regression analysis
      for fatty liver showed that only anti-HCV antibodies sero-positivity had
      statistically significant odds ratio in comparison to chromium level and
      aflatoxin B1. It is concluded that some heavy metals, and Aflatoxin B1 had a
      definite association with liver diseases in the area under study. Having anti-HCV
      antibodies had a relation with fatty liver and with bilharzial liver more than
      having HBsAg. It is recommended that environmental management to factories nearby
      the village is urgently needed to decrease exposure to heavy metals. Prevention
      of hepatitis infection and aflatoxin exposure through different means is also
      recommended, other wise health care authorities would be confronted with unusual
      cases of HCC in the nearby future.

PMID- 16900615
TI  - Evaluation of medical waste incinerators in Alexandria.
AB  - Medical establishments play important roles in different activities by using of
      modern technology to serve the humans and the environment through different
      departments in the establishment and its firms. Medical wastes are considered as
      a hazardous waste because they contain toxic materials, infectious, or non
      infectious wastes and they are considered as a hazard to millions of patients,
      health care workers, and visitors. Treatment processes for medical wastes
      comprise autoclaving, microwaving, chemical disinfection, irradiation, plasma
      system, and incineration. Incineration is a thermal process, which destroys most
      of the waste including microorganisms. Combustion process must be under
      controlled conditions to convert wastes containing hazardous materials into
      mineral residues and gases. Hospital waste incinerators may emit a number of
      pollutants depending on the waste being incinerated. These pollutants include
      particulate matter, acid gases, toxic metals, and toxic organic compounds
      products of incomplete combustion, e.g., dioxins, furans, and carbon monoxide, as
      well as sulfur oxides and nitrogen oxides. So, there should be a reduction of
      emissions of most of these pollutants by air pollution control devices. This
      study was conducted in 51 medical establishments (ME) in Alexandria. To evaluate
      its incinerators. It was found that only 31.4% of total ME have their own
      incinerators to treat their medical waste. Also, the incinerators conditions were
      poor with incomplete combustion. So, the study recommend handling of all medical
      wastes of ME in Alexandria by the company which is responsible now for management
      of domestic solid wastes of the city.

PMID- 16900616
TI  - Assessment of combustion products of medical waste incinerators in Alexandria.
AB  - The emissions and ashes from medical waste incinerators might perform a threat to
      the environment and the public health. The aim of the present work is to evaluate
      the emissions and ashes of six medical wastes incinerators in six hospitals in
      Alexandria. Five air pollutants were sampled and analyzed in the emissions
      comprising smoke, lead, carbon monoxide, sulphur dioxide and nitrogen dioxide .
      Ash samples were analyzed for bacterial count, volatile substances, lead and
      cadmium. Shape and color of ash were observed visually. The results of the
      present study have revealed that all the average values of gases in the six
      incinerators were within the limits stated in Egyptian environmental law, where
      as carbonaceous particulate (smoke) averages of the six incinerators have
      exceeded the maximum allowable limit in the law. On the other hand, lead
      concentration in emissions were far below the maximum allowable limit in the law.
      Incinerator No 6 emissions have been significantly higher in CO, NO2, SO2 and
      smoke concentration than the other five incinerators P<0.001, P<0.0006, P<0.0001,
      and P<0.002 respectively. There was no significant variation in bacterial count
      of ash samples at 20 degrees C and 37 degrees C between the six studied
      incinerators. Volatile substance percentage of ash samples in the six
      incinerators were much higher than the recommended percentage. There was a highly
      significant variation between the six incinerators (p<0.005). Lead and cadmium
      concentrations in ash samples were much higher than those in developed countries,
      meanwhile, more or less as those in developing countries. It is recommended to
      state specific realistic emissions limits for medical waste incinerators and to
      substitute sporadic incinerators in hospitals by two central incinerators in
      proper places outside the city.

PMID- 16900617
TI  - Evaluation of occupational hazards in foundries.
AB  - The working environment of foundries is hazardous and characterized by multiple
      simultaneous chemical, physical and mechanical hazards exposure, which would lead
      to injuries of foundry workers. The aim of the present work is to evaluate
      occupational hazards in four foundries, two in Alexandria: El Nasr and Ramsis,
      and two in Behira: Misr Spinning and Weaving and Misr Rayon companies. Levels of
      total and respirable dust, free silica % in total dust and lead concentration in
      total and respirable dust; NO2, SO2 and CO concentrations; noise and heat stress
      levels have been determined in the present work. Occupational injuries data were
      analyzed in a three years period from 1998 to 2000. The results of the present
      work revealed; 1. The levels of total dust and respirable dust exceeded the
      threshold limit values at knockout and cleaning operations at El Nasr Company. 2.
      Free silica percentage exceeded permissible levels in all operations except
      pouring in El Nasr Company. 3. CO levels in Misr Spinning and Weaving Company
      were higher than threshold levels. 4. Noise levels in knockout and cleaning
      operations at the four companies were exceeding the threshold limit values. 5.
      Heat stress levels in melting and pouring operations in El Nasr and in pouring
      operation in Ramsis Company were higher than the maximum permissible levels. 6.
      The age group 31-40 years has recorded the highest average incidence rate of
      injuries of age groups (P<0.01). 7. Lower extremities and higher extremities have
      recorded the highest average incidence rate in the four companies (P<0.001-P<0.01
      respectively). 8. Transportation and lifting was the main cause of injury in the
      four companies (P<0.05). 9. Faulty action and striking against was the main mean
      of injury in the four companies (P<0.01). 10. Ramsis Company has the highest
      average incidence rate in almost all injuries parameters and indices (frequency
      rate and severity rate) (P<0.05-P<0.001). The present work is a massive survey,
      which highlights the occupational hazards in Egyptian foundries.

PMID- 16900619
TI  - Psychosocial characteristics of diabetic students at Sporting Students Hospital
      in Alexandria.
AB  - Type 1 diabetes mellitus is a chronic disease that may have an impact on
      children's psychosocial adjustment. The aim of the present work was to study the
      psychosocial characteristics of diabetic students and to determine predictors of
      diabetes control. A cross-sectional study of 150 diabetic students who attended
      the diabetic school health insurance clinic of Sporting Student's Hospital in
      Alexandria governorate within a period of one month was conducted. A pre-designed
      interviewing questionnaire was used to collect--from the child and/or his/her
      parents--personal data, data about the child social relationships and school and
      disease characteristics. School adjustment index and stress symptom index were
      used to assess the school performance and the stress symptoms respectively. The
      result revealed that 34% of the diabetic students were maladjusted to school and
      31.3% were symptomatic based on the stress index. Generally speaking, diabetic
      children reported good relationship to peers (65.3%), parents (57.3%) and
      siblings (51.3%), most of them have good friendship (82%) and those involved in
      one or more kind of hobby were about three fourth of all. Both age (P<0.05), sex
      (P<0.05), social class (P<0.05), disease duration (P<0.05) and stress symptoms
      (P<0.05) were all significantly associated with the disease control. However
      after adjustment for other variables, students of low social class families
      (OR=5.1, p<0.01) and those of longer disease duration (6-10 years) (OR=7.9,
      p<0.05) were significant predictors of diabetes control. In conclusion diabetes
      per se might have no significant association with academic performance or social
      relationship. Students with large diabetic duration-especially those of low
      social class families--are at increased risk of suboptimal glycaemic control and
      should be targeted for interventional strategies.

PMID- 16900618
TI  - A study of the association between delayed type hypersensitivity reaction to
      mycobacterium tuberculosis and atopy in asthmatic children.
AB  - The purpose of this study was to investigate if there is an inverse association
      between Mycobacterium tuberculosis infection and atopy among children living in
      rural and semi urban areas in El Behira governorate, Egypt. METHODS: All the
      studied children were BCG vaccinated in their newborn period. In Tuberculin
      testing, indurations greater than or equal to 5 mm were accepted as positive. For
      atopy, the most common aeroallergens were used in skin intradermal testing, and
      reactions > or = 3 mm were accepted as positive. RESULTS: Among 150 studied
      children whose ages ranged from 4-8 years, 89 patients were purified protein
      derivative (PPD) negative whereas in 61 patients PPD was positive. Among the PPD
      negative patients skin intradermal test was positive for atopy in 51.6% (n = 46),
      while among the PPD positive patients skin intradermal test was positive in 52.4%
      (n = 32). As the two groups were compared for having positive intradermal skin
      test reaction, no statistically significant difference was detected between them
      (p >0.05). CONCLUSIONS: In this study no statistically significant difference was
      detected between Mycobacterium tuberculosis infection as indicated by positive
      PPD positivity and atopy tested by skin intradermal injection of common
      aeroallergens.

PMID- 16900620
TI  - [Advances in medical oncology].
AB  - Medical oncology is playing an increasingly important role in multi-disciplinary
      modality in cancer management. Advances in medical oncology has brought new
      improvement in efficacy in the treatment of various malignant diseases, such as
      lymphomas, breast cancer, non-small lung cancer, and gastrointestinal tract
      carcinomas. In medical oncology, traditional cytotoxic agents remains to be
      indispensable, while molecular targeted therapy has been introduced into routine
      clinical practice as a promising approach. Meanwhile, researches on supportive
      therapy is continuously refining.

PMID- 16900621
TI  - [Management of head and neck cancer: current practice and future prospect].
AB  - Researches on head and neck oncology has been going on for only several decades,
      and the treatment levels of these tumors vary in our country. This article
      provides a brief status quo overview and future prospect of head and neck
      oncology, focusing on multimodality therapy, I-staged reconstruction, organ
      preservation, surgical management, survival rates, and promising advances.

PMID- 16900622
TI  - [Symptoms and prognosis of nasopharyngeal carcinoma].
AB  - OBJECTIVE: To study the relationship between the symptoms and prognosis of
      nasopharyngeal carcinoma (NPC). METHODS: The clinical data of 905 M0 NPC patients
      who received radical radiotherapy from January 1990 to May 1999 were
      retrospectively studied. Nodal distribution, cranial nerve paralysis, as well as
      the relationship between symptom duration and prognosis were analyzed. RESULTS:
      The most common symptom in patients with NPC is neck node metastasis, with an
      incidence of 40.0% at the time of diagnosis, followed by blood-staining sputum
      (18.7%) and aural symptoms (17.0%). Node metastasis in the lower neck and
      supraclavicular region alone was seen in 10 patients (1.1%). Cranial nerve
      paralysis was found in 179 patients (19.8%). The 5-year overall survival and
      disease-free survival were significant lower in symptom duration more than 6
      months group than in less than 6 months group (71.2% vs 79.8%, P = 0.008 and
      51.9% vs 63.6%, P = 0.0008); however, the local control rate between these two
      group was not significantly different (79.4% vs 83.5%, P = 0.138). CONCLUSION:
      The symptom duration is associated with the prognosis of NPC. Early diagnosis and
      treatment are the most important factors in improving the prognosis of NPC.

PMID- 16900623
TI  - [Clinical treatment of small hepatocellular carcinoma].
AB  - OBJECTIVE: To evaluate the suitable treatment methods of small hepatocellular
      carcinoma (SHCC). METHODS: From 2000 to 2004, 849 cases of SHCC (< or = c5 cm)
      were enrolled and divided into two groups: resection group (n = 406) and
      minimally invasive treatment (MIT) group (n = 443). The survival rates,
      recurrence rates, and post-treatment complications were compared retrospectively.
      RESULTS: The 3-year survival rate in the resection group was 72.1%. The 3-year
      survival rates in tumor < or = 3 cm and tumor 3-5 cm of resection group were
      73.3% and 70.5% (P = 0.46), respectively. The 1-year, 2-year, and 3-year
      recurrence rates in resection group were 13.5%, 29.9%, and 39.8%, respectively.
      The 3-year survival rates in MIT group was 73.8%. The 3-year survival rates in
      tumor < or = 3 cm and tumor 3-5 cm of MIT group were 74.7% and 72.2% (P = 0.45),
      respectively. The 1-year, 2-year, and 3-year recurrence rates in MIT group were
      12.6%, 28.7%, and 40.4%, respectively. The 3-year survival rate was significantly
      different between these two group in tumor < or = 3 cm (P < 0.05). The post
      treatment complication rates of these two group were 30.8% and 6.1% (P < 0.01),
      respectively. CONCLUSIONS: MIT is as effective as the traditional resection in
      SHCC. However, MIT is superior to the traditional resection in terms of minimal
      invasion and less post treatment complication rate. The recurrence rate of HCC
      was still high after treatment. Comprehensive therapies, including MIT, may
      increase the survival rate and life quality in SHCC patients.

PMID- 16900624
TI  - [A retrospective analysis of anaplastic thyroid carcinoma].
AB  - OBJECTIVE: To summarize the new knowledge of the anaplastic thyroid carcinoma
      (ATC). METHODS: The clinical data of 58 patients (35 men, 23 women, aged 28 to 79
      years) with ATC that were treated with various therapeutic modalities from 1981
      to 2005 were retrospectively analyzed. Among them, 25 patients received surgery
      alone (SA group) and 33 received surgery plus radiation (S + R group). The dosage
      of postoperative radiotherapy was 40-70 Gy. Four patients received biopsy, 24
      received palliative surgery, and 30 received radical surgery. Only 2 patients
      received complete chemotherapy. RESULTS: ATC invaded trachea in 40 patients
      (69.0%), esophagus in 32 patients (55.2%), and carotid in 17 patients (29.3%).
      The cervical lymph node metastases occurred in 19 patients (32.8%). The overall 1
      year survival rate was 37.8%, 3-year survival rate 31.2%, and 5-year survival
      rate 25.9%. The 5-year survival rate was 37.8% in S + R group but was only 9.9%
      in SA group (P = 0.0000). The 5-year survival rate was 41.4% in radical surgery
      subgroup but was only 12.4% in palliative surgery subgroup (P = 0.0023). In < or
      = 45-year-old subgroup (n = 4), the 5-year survival rate was 50.0%; however, in >
      45-year-old subgroup, it was only 21.3%. In postoperative radiation < 60 Gy
      subgroup , the 5-year survival rate was 19.3%; however, in > or = 60 Gy group, it
      was 53.7% (P = 0.0000). Among all the 58 patients, some patients received
      palliative surgery because of tumor invasion in trachea (n = 16, 27.6%),
      esophagus (n = 8, 13.8%), carotid (n = 8, 13.8%), and other sites (n = 13,
      22.4%). Twenty-four patients (61.5%) died of localrelapse, 2 (5.1%) of cervical
      lymphnode failure, 9 (23.1%) of metastasis, and 4 (10.3%) of other reasons.
      CONCLUSIONS: The prognosis of ATC is poor. Radical surgery and postoperative
      radiation > or = 60 Gy can improve the survival rate. Tumor invasion in trachea,
      esophagus, and carotid are the main reasons of palliative surgery. Local relapse
      is lethal.

PMID- 16900625
TI  - [Experimental study of preventing postoperative stenosis by modifying artificial
      esophagus in dogs].
AB  - OBJECTIVE: To observe the effect of the modified artificial esophagus on
      postoperative stenosis in dogs. METHODS: The models of defected esophagus were
      established in dogs. The double-layered membrane tube (modifying type) was
      implanted in the test group (n = 10) and the esophageal stent was further
      inserted when the stenosis occurred. The single pattern tube (original type) was
      transplanted to the control group (n = 30). The dilation treatment was performed
      to relieve the postoperative stenosis; alternatively, the esophageal stent was
      implanted in the unsuccessful dogs. RESULTS: The average artificial esophagus
      removal time was 19.10 days in the test group, which was significantly lower than
      39.07 days in the control group (t = 15.6, P = 0.000). No obstruction after
      removal was observed in the experimental group. The incidence of postoperative
      stenosis had no significant difference between these two groups. CONCLUSION: The
      double-layered membrane tube can make the tube removal safer by shortening the
      removal time.

PMID- 16900626
TI  - [Surgical treatment of primary small-cell esophageal carcinoma].
AB  - OBJECTIVE: To explore the surgical treatment of primary small-cell esophageal
      carcinoma (PSEC). METHODS: We retrospectively analyzed the clinical data of 73
      patients with PSEC who received surgical treatment in our hospital from 1984 to
      2003. RESULTS: The overall resection rate was 94.5%. The complete resection rate
      was 89.0% and operation mortality was 1.4%. The 1-year, 3-year, and 5-year
      survival were 50.7%, 13.7%, and 8.2%, respectively. CONCLUSIONS: PSEC is a rare
      malignant tumor with poor prognosis. Surgical resection is the main method for
      patients in stage I or II, and postoperative chemotherapy seems to be helpful.
      Patients in stage Ill or IV should be managed with chemotherapy and radiotherapy.

PMID- 16900627
TI  - [Diagnosis and treatment of patients with cholangiocarcinoma].
AB  - OBJECTIVE: To explore the diagnosis and treatment of the cholangiocarcinoma.
      METHODS: Forty one patients with cholangiocarcinoma who were enrolled in our
      hospital from January 1970 to January 2005 were retrospectively analyzed.
      RESULTS: Among these 41 patients, the 1, 3, and 5-year survival rate was 82.3%,
      45.8%, 45.8%, respectively, with radical operation, and was 11.0%, 0, 0 with non
      radical operation (chi2 = 21.38, P < 0.01). The 1-year and 3-year survival rate
      was 11.0% and 0 in 9 patients treated with laparatomy, which was not
      significantly different from those treated with non-radical operation (chi2 =
      0.02, P = 0.89). Four patients did not receive operation and all died within one
      year. Among 25 patients who did not experience lymph node metastasis, the 1, 3,
      and 5-year survival rate was 58.4%, 27.3%, and 27.3%. Among 16 patients who were
      found lymph node metastasis, the 1-year and 3-year survival rate was 61.8% and 0
      (chi2 = 13.85, P < 0.01). CONCLUSION: Operation is the most effective treatment
      for cholangiocarcinoma. Radical operation is the only curative treatment.

PMID- 16900628
TI  - [Nephron-sparing surgery for 69 patients with renal tumors].
AB  - OBJECTIVE: To evaluate the results of nephron-sparing surgery (NSS) for renal
      tumors. METHODS: A retrospective analysis was performed for the clinical data of
      66 patients who were affected by renal tumors and treated with NSS. RESULTS:
      Among 66 cases, 63 were treated with partial nephrectomy and 6 with enucleation.
      The renal vessel was clamped in 45 cases intraoperative. The histological
      subtypes included clear cell carcinoma in 40 cases, papillary renal cell
      carcinoma (RCC) in 2 cases, chromophobe RCC in 2 cases, angiomyolipoma in 24
      cases, and adenoma in one case. Surgical margins were negative in all cases.
      Seven patients had postoperative complications and no perioperative acute renal
      failure occurred. Among 44 cases with renal cell carcinoma, 42 were followed for
      mean 55.4 months. The overall and disease-free 5-year survival rates were 97.3%
      and 90.7%, respectively. CONCLUSION: NSS is a effective and safe operation for
      selected patients with renal tumors, providing functional advantage gained by the
      maximal preservation of unaffected renal parenchyma without sacrificing cancer
      control.

PMID- 16900629
TI  - [Efficacy of once-per-cycle administration pegylated recombinant human
      granulocyte colony-stimulating factor in chemotherapy-induced neutropenia in a
      phase I trial].
AB  - OBJECTIVE: To explore the efficacy of pegylated recombinant human granulocyte
      colony-stimulating factor (PEG-rhG-CSF) in the prophylaxis of chemotherapy
      induced neutropenia. METHODS: Patients with previously untreated non-small cell
      lung cancer or breast cancer and with normal bone marrow function were eligible
      for the trial. In the phase I trial, patients were to treated with two cycles of
      paclitaxel/carboplatin chemotherapy every 21 days. In cycle 1, if absolute
      neutrophil count (ANC) dropped below 1.0 x 10(9)/ L with fever and/or ANC dropped
      below 0.5 x 10(9)/L, rhG-CSF 150 microg/d was administrated until WBC > or = 10 x
      10(9)/L or ANC > or = 5.0 x 10(9)/L. In cycle 2, patients were to receive a
      single injection of PEG-rhG-CSF (30, 60, 100, or 200 microg/kg) 48 hours after
      chemotherapy. Pharmacodynamic analyses were performed. RESULTS: All the 16
      patients enrolled (4 in each group) were eligible for efficacy evaluation. In
      cycle 1, 7 patients received rhG-CSF administration because of grade 4
      neutropenia, while in cycle 2, there was only 1 episode of grade 4 neutropenia,
      which were in the 30 microg/kg group. In cycle 1, the mean ANC nadir of 1.37 x
      10(9)/L occurred on day 13 in the 9 patients who received no rhG-CSF
      administration. In cycle 2, the mean ANC nadirs were 0.77 x 10(9)/L, 4.54 x
      10(9)/L, 3.00 x 10(9)/L, and 5.56 x 10(9)/L, respectively, in 30, 60, 100, or 200
      microg/kg group. The nadirs of the first two groups occurred on day 8 of cycle 2,
      while those of the other two groups appeared on day 7. After PEG-rhG-CSF
      administration, two mean ANC peaks were observed. The first one ranging from
      20.87 x 10(9)/L to 33.61 x 10(9)/L in the 4 groups appeared on day 3 to day 4. In
      the 30 microg/ kg group, the mean ANC reached the second peak at 5.03 x 10(9)/L
      on day 14. The second peaks on day 10 in the other groups were 12.42 x 10(9)/L,
      11.59 x 10(9)/L, and 18.92 x 10(9)/L, respectively. Pharmacodynamic analyses
      showed sustained serum concentrations of PEG-rhG-CSF during the period of
      neutropenia. CONCLUSIONS: PEG-rhG-CSF administration may decrease the incidence
      of grade 4 neutopenia and result in earlier and higher nadir ANCs. PEG-rhG-CSF
      has a potential of once-per-cycle administration. The ANC and serum concentration
      of PEG-rhG-CSF are consistent with neutrophil receptor-mediated clearance.

PMID- 16900630
TI  - [Effect of combination of glutamine and mitomycin C on human gastric carcinoma
      cell strain MGC-803].
AB  - OBJECTIVE: To evaluate the effect of combination of glutamine (GLN) and mitomycin
      C (MMC) on the human gastric carcinoma cell line MGC-803 in vitro. METHODS: The
      effects of GLN and MMC were measured by MTT assay, and the interaction between
      the two agents was evaluated by the median-effect principle. Flow cytometry was
      used for cell cycle analysis. RESULTS: GLN did not significantly stimulate the
      cell growth in vitro. High-concentration of GLN could inhibit the cell growth.
      MMC could effectively inhibit the cell growth in a time-dependent manner. The
      interaction of these two agents showed a weak antagonistic activity (1 < CI <
      1.2703). MMC induced remarkable S-phase arrest. Low-dose GLN has limited effect
      on the S-phase arrest of MMC, while high-dose GLN significantly attenuated the S
      phase arrest and lowered the proliferation index of MGC-803 cell. CONCLUSIONS:
      Combination of GLN and MMC has a a weak and dose-dependent antagonistic activity
      in the treatment of gastric carcinoma cell line MGC-803. The combination of high
      dose MMC and low-dose GLN may achieve better efficacy.

PMID- 16900631
TI  - [Application of monoclonal antibody immobilized polyurethane film for site
      specific gene therapy].
AB  - OBJECTIVE: To study the feasibility of delivering viral gene vector from a
      collagen-coated polyurethane (PU) film through a mechanism involving monoclonal
      antiviral antibody tethering. METHODS: Anti-adenoviral monoclonal antibodies were
      covalently bound to the collagen-coated PU surface. These antibodies enabled
      tethering of replication defective adenoviruses through highly specific antigen
      antibody affinity. The PU film-based gene delivery using antibody-tethered
      adenovirus encoding green fluorescent protein (GEP) was tested in rat arterial
      smooth muscle cell (A10 cell) culture in vitro. The virus binding stability was
      studied by incubating the collagen-coated PU film in PBS solution at 37 degrees C
      for 20 days, followed with A10 cell cultures with the incubated films and the
      corresponding buffer solution. RESULTS: PU films with antibody-tethered
      adenovirus encoding GFP demonstrated efficient and highly localized gene delivery
      to A10 cells. Virus binding was stable for at least 10 days at physiological
      conditions, more than 77% of the originally bound virus remained in the film
      after 15 day's incubation. CONCLUSION: Gene delivery using PU film-based anti
      viral antibody tethering of vectors exhibited potentials of applications in a
      wide array of single or multiple therapeutic gene strategies, and in further
      stent-based gene delivery therapeutic strategies.

PMID- 16900632
TI  - [Duration of tau hyperphosphorylation and spatial memory deficit induced by
      single injection of Forskolin into lateral ventricle of rat].
AB  - OBJECTIVE: To investigate the duration of tau hyperphosphorylation and spatial
      memory retentive deficit induced by single injecting with Forskolin, a protein
      kinase A activator, into lateral ventricle of rats, and the correlation between
      the two pathological alterations. METHODS: Forskolin (80 micromol/L, 40 microl)
      was injected into the lateral ventricle by stereotaxic injection. Tau
      phosphorylation and spatial memory retention were measured by Western
      blot/immunocytochemistry and Morris-Water-Maze test, respectively. RESULTS: The
      phosphorylation levels of tau at Tau-1, PHF-1, and pS214 epitopes were
      significantly elevated at 24, 48 and 72 h after single administration of
      Forskolin (P < 0.05). The most significant elevation was seen at 48 h (P < 0.01)
      and it tended to recover at 72 h (P < 0.05) after injection. The correlation
      between the two pathological alterations was positive at PHF-1 site (r = 0.97, P
      < 0.05), negative at Tau-1 site (r = -0.963, P < 0.05), and not significant at
      pS214 site (r = 0.705, P > 0.05). CONCLUSIONS: Forskolin can induce tau
      hyperphosphorylation and spatial memory retentive deficit within a certain period
      of time. The level of tau phosphorylation in hippocampus is somehow correlated
      with the spatial memory deficit in rats.

PMID- 16900633
TI  - [Localization and differentiation of hair follicle stem cells].
AB  - OBJECTIVE: To identify the localization of hair follicles stem cell (HFSC) in
      different stages of hair and explore the differentiating capacity of HFSC into
      epidermis in vitro. METHODS: HFSC were detected by K19 immunostaining in normal
      human skin. Then, the isolated HFSC through enzyme digestion were seeded on
      dermal equivalent (DE) and cultured between the air-liquid interfaces for 14
      days. Skin-equivalents was harvested and used for evaluation. RESULTS: HFSC
      mainly located in outer root sheet in hair follicle and human anagen hair
      follicles containing two distinct reservoirs for K19-positive cells located in
      the bulge and bulb of the follicle. These two reservoirs fused in line of outer
      root sheets during the catagen-telogen transition phase and individualized again
      in the newly forming anagen hair follicle. Based on DE, growing HFSC built a
      multilayered and confined epidermis. CONCLUSION: HFSC located in outer root
      sheets can promote hair cycle and differentiate into epidermis in vitro.

PMID- 16900634
TI  - [Hemangiopoiet in modulates adhesive properties of endothelial cells].
AB  - OBJECTIVE: To explore the effect of hemangiopoietin (HAPO) on the adhesive
      properties of human umbilical vein endothelial cells (HUVEC). METHODS: The
      adhesion of HUVEC and the expressions of CD54, CD102, CD106, CD31, CD62E, and
      CD62P were measured by adhesion assay, flow cytometry, and semi-quantitative RT
      PCR. RESULTS: HAPO enhanced the total adherence of HUVEC in a concentration
      dependent manner. Flow cytometry analysis revealed that the treatment of HAPO
      resulted in a significantly increased expression of CD106 and CD62E on HUVEC in a
      time-dependent manner. When HUVEC were incubated with HAPO for 6 h, the
      percentage of CD106 + HUVEC and CD62E HUVEC increased about 2.10 folds and 5.84
      folds, respectively, compared with control. The time-course of adhesive molecules
      mRNA expression indicated that the expression of CD106 and CD62E reached at the
      maximum 1.86 folds and 6.16 folds, respectively, compared with control.
      CONCLUSION: HAPO may facilitate the homing of hematopoietic stem/progenitor
      cells.

PMID- 16900635
TI  - [Collection of a Chinese pedigree with Parkinson's disease and linkage analysis
      of nine susceptibility genes].
AB  - OBJECTIVE: To analyze the susceptibility genes of a Parkinson's Disease (PD)
      family. METHODS: The blood samples of a four-generation classic idiopathic PD
      family were collected. Two-point LOD score method was applied to analyze the
      linkage disequilibrium between the disease locus and microsatellite markers.
      RESULTS: We studied 13 markers near the 9 genes that had been reported to be
      associated with PD. No obvious evidence showed that the selected markers had
      anything correlation with PD locus. CONCLUSION: These 9 genes are not the
      susceptibility genes of PD in this family.

PMID- 16900636
TI  - [Root microstructure and distribution of the endophytic fungi in Taxus chinensis
      var. mairei].
AB  - OBJECTIVE: To study the root microstructure and the distribution of the
      endophytic fungi in Taxus chinensis var. mairei. METHODS: The roots of Taxus
      chinensis var. mairei at nature were cut with paraffin, dyed and observed by
      microscope. RESULTS: The secondary structure of the roots of Taxus chinensis var.
      mairei consisted of the periderm and vascular cylinder (stele). Axial and radial
      systems formed the secondary xylem of the roots. Tracheids and xylary parenchyma
      cells constituted the axial system, and xylary radial formed the radial systems.
      The secondary phloem consisted of sieve cells and phloem parenchymas. Only a
      small quantity of phloem fibers were distributed in the secondary phloem, and the
      phloem ray was unconspicuous. Many endophytic mycelia penetrated in the velamina.
      CONCLUSIONS: The secondary structure of the root of Taxus chinensis var. mairei
      accords with that of other gymnosperms and dicotyledons, although its secondary
      xylem is constituted with tracheids and sieve cells. The endophytic mycelia
      exists in the local cells of velamina in the roots of Taxus chinensis var.
      mairei.

PMID- 16900637
TI  - [Distribution and expression of peroxisome proliferator activated receptor gamma
      in human pituitary adenomas].
AB  - OBJECTIVE: To evaluate the distribution and expression of peroxisome proliferator
      activated receptor gamma (PPAR-gamma) in human pituitary adenomas. METHODS:
      Thirty eight consecutive surgically resected pituitary adenomas and 5 normal
      pituitary tissues were enrolled in the study. Immunohistochemistry was used to
      confirm the distribution of PPAR-gamma. Expression of PPAR-gamma was evaluated by
      Western blot. RESULTS: PPAR-gamma immunoreactivity was located in the nucleoli of
      pituitary adenoma cells. PPAR-gamma was expressed in all human pituitary adenomas
      and normal pituitary tissues. Its expression in pituitary adenomas was
      significantly higher than in normal pituitary tissues (P < 0.01), and its
      expression in ACTH-secreting adenomas was significantly higher than in any other
      type of pituitary adenomas (P < 0.05). CONCLUSIONS: PPAR-gamma may play an
      important role in the generation, growth, and invasion of human pituitary
      adenomas. It may become a novel therapeutic target for these tumors.

PMID- 16900638
TI  - [Prevalence of bacterial vaginosis in married women of reproductive age in the
      rural area of Shandong province and its risk factors].
AB  - OBJECTIVE: To explore the prevalence of bacterial vaginosis of married women of
      reproductive age in the rural area of Shandong province and its affecting
      factors, with an aim to provide references for setting up preventing measures for
      this disease. METHODS: A stratified, population-based, cluster sampling method
      was employed. The epidemiological investigation on bacterial vaginosis of married
      women of reproductive age was carried out at four sampling fields. RESULTS: The
      prevalence of bacterial vaginosis was 6.64%. The main risk factors included:
      lacked of personal bathtub and towel; did not use sterilized paper on menstrual
      phase; had no knowledge that gonorrhea, syphilis, AIDS, and trichomonal vaginitis
      can be transmitted through sexual intercourse. CONCLUSION: The prevalence of
      bacterial vaginosis in married women of reproductive age in Shandong rural area
      is high, which correlates with the lower education level, limited health
      knowledge, and unhealthy behavior.

PMID- 16900639
TI  - [Toxic effect of butenolide on chondrocyte differentiation and the protective
      effect of selenium].
AB  - OBJECTIVE: To study the effect of butenolide (BUT) on cultured chondrocytes
      differentiation and the possible protective effects of selenium (Se). METHODS: Ex
      vivo cultured chondrocytes were divided into six groups: (1) Control group
      (without BUT and Se); (2) Se 0.1 microg/ml control group; (3) BUT 0.1 microg/ml
      group; (4) BUT 1.0 microg/ml group; (5) BUT 5.0 microg/ml group; and (6) BUT 1.0
      microg/ml + Se 0.1 microg/ml group. The expression of collagen II (Col II),
      collagen X (ColX), basic fibroblast growth factor (bFGF), and parathyroid hormone
      related peptide (PTHrP) in (or around) chondrocytes in all groups were analyzed
      by immunohistochemistry. RESULTS: The expressions of Col II in 1.0 microg/ml BUT
      group and 5.0 microg/ml BUT group were significantly lower than those in the
      control group (P < 0.05). The expression of Col II in 1.0 microg/ml BUT + Se
      group were significantly higher than those in the 1.0 microg/ml BUT group and 5.0
      microg/ml BUT group (P < 0.05). The expressions of bFGF and PTHrP of BUT groups
      were significantly higher than those in the Se and control groups (P < 0.05). No
      expression of ColX was observed in all groups. CONCLUSION: BUT can affect the
      collagen II synthesis of the chondrocytes. Selenium supplementation may play a
      protective role.

PMID- 16900640
TI  - [Dynamics of T lymphocyte subsets in HAART treated AIDS patients with successful
      suppression of HIV replication and different CD4 + T cell restoration].
AB  - OBJECTIVE: To study the dynamic changes of T lymphocyte subsets of AIDS patients
      during more than 24 months of highly active antiretrovirus therapy (HAART) with
      successful suppression of HIV replication and different CD4 + T cell restoration.
      METHODS: Totally 45 AIDS patients who had received HAART for more than 24 months
      were included. During HAART (including DO, M3, M6, M12, M18, and M24), the number
      of plasma HIV-1 RNA was measured quantitatively using the bDNA assay, and T
      lymphocyte subsets including CD3 + CD4 + cells, CD3 + CD8 + cells, naive CD4 +
      cells (CD4 + CD45RA + CD62L +), CD4 + CD28 + cells , and CD8 + CD38 + cells were
      detected with flow cytometer. RESULTS: Among 45 patients, 24 patients (53.3%)
      whose plasma viral load decreased to less than 500 copies/ml at M6 and maintained
      to M24 were classified into three groups according to the CD4 + T cell count
      increments on M24 (compared with DO): group A (< 100/mm3), group B (100-200/mm3),
      and group C (> 200/mm3). After the initiation of HAART, T lymphocyte response,
      including CD4 + T cell counts, naive CD4 + cell counts, percentages of CD4 + CD28
      + cells in these patients were improved gradually, while CD8 + CD38 + percentage
      decreased. The improvement of T lymphocyte response in group C was most
      remarkable even with highest plasma viral load and lowest CD4 T cell count on DO.
      Compared with group A and B, group C had significantly better improvement not
      only in the quantities of CD4 + T cell, but also in the CD28 + expression and
      naive CD4 + T cell populations. CONCLUSIONS: T lymphocyte response of AIDS
      patients can be effectively reconstituted by HAART. Different dynamics of CD4 +
      CD28 + and naive CD4 + populations may considerably contribute to the quantity
      and cellular function restoration of CD4 + T lymphocyte.

PMID- 16900641
TI  - [Pathological study of pulmonary carcinomas with spindle and/or giant cells].
AB  - OBJECTIVE: To study the pathologic features of pulmonary carcinomas with spindle
      and/or giant cells. METHODS: Twenty cases of pulmonary carcinomas with spindle
      and/or giant cells were studied by using lightmicroscopy and immunohistochemical
      staining. RESULTS: Of 20 cases, 15 cases were pleomorphic carcinoma (10 cases
      with adenocarcinoma, 3 cases with large cell carcinoma, 1 case with squamous cell
      carcinoma and 1 case with giant cell carcinoma) , 4 cases were spindle cell
      carcinoma, and 1 case was giant cell carcinoma. Immunohistochemical results
      showed AE1/AE3 was positive in the spindle and/or giant cell component of 19
      cases, Vimentin was positive in the spindle and/or giant cell component of 20
      cases, P53 was positive in 10 cases and thyoid transcription factor-1 (TTF-1) was
      negtive in all cases. CONCLUSIONS: Pulmonary carcinomas with spindle and/or giant
      cells is definded as a group of poorly differentiated non-small cell carcinoma
      that contains a component of spindle and/or giant cells. The diagnosis is based
      on histopathology and immunohistochemical staining of AE1/AE3 and Vimentin.

PMID- 16900642
TI  - [Clinical evaluation of high-risk HPV detection by hybrid capture II in screening
      cervical intraepithelial neoplasma].
AB  - OBJECTIVE: To evaluate the value of high-risk HPV (hrHPV) detection by Hybrid
      Capture II (HC2) in screening cervical intraepithelial neoplasm (CIN). METHODS:
      Totally 723 patients who had received a dual screening with thinprep cytologic
      test (TCT) and HC2 in our department were analyzed retrospectively. Among them,
      350 patients received a triple examination with TCT, HC2, and colposcopic biopsy.
      RESULTS: Among the 723 patients, the incidences of hrHPV infection with atypical
      squamous cell (ASC), low squamous intraepithelial lesion, and high squamous
      intraepithelial lesion were 70.7% (94/133), 88.9% (249/280), and 90.9% (90/99),
      respectively, significantly higher than 55.5% (117/211), the incidence of hrHPV
      infection with normal cytological results (P = 0.005, P < 0.001, P < 0.001,
      respectively). Among 350 cases who were received triple examination, the
      incidence of hrHPV infection with cervical intraepithelial neoplasia (CIN) 1 and
      CIN 2 were 88.9% (72/81) and 96.3% (52/54), significantly higher than 77.7%
      (153/197), the incidence of hrHPV infection with normal pathological results (P =
      0.03, P = 0.002); The incidence of hrHPV infection with CIN 3 and squamous cancer
      were 91.7% (11/12) and 100.0% (6/6), also higher than normal cases. Among these
      350 cases, the incidence of hrHPV infection with ASC was 79.3% (69/87). The
      incidence of CIN 2-3 with ASC and hrHPV infection was 38.0%, significantly higher
      than the incidence of CIN 2-3 with ASC and without hrHPV infection (5.9%) (P =
      0.04). CONCLUSION: hrHPV infection has a close relation with CIN, and the
      incidence of hrHPV infection increases along with the severity of CIN.

PMID- 16900643
TI  - [Simultaneous occlusal orthodontics during mandibular distraction osteogenesis].
AB  - OBJECTIVE: To study the significance and principle of simultaneous orthodontics
      during mandibular distraction osteogenesis. METHODS: Totally 11 patients
      simultaneously underwent occlusal orthodontic treatment for 3-4 months during
      mandibular distraction osteogenesis. Square-wire and elastic loops were adapted
      to perform the orthodontics by ways of more frequent adjustment of orthodontic
      device than routine method. RESULTS: All 11 patients with mandibular micronathia
      obtained the improved occlusion with their mandibular expected elongation, for
      instance, their open-bite and teeth displacement were partially corrected.
      CONCLUSION: Simultanous orthodontics with mandibular distraction osteogenesis may
      improve the malocclusion, decrease the orthodontic time, and lead the mandibular
      distraction direction.

PMID- 16900644
TI  - [Relationship between the quantitative structural study of lung and the right
      ventricle outflow tract reconstruction in infants with tetralogy of Fallot].
AB  - OBJECTIVE: To analyse the relationship between the quantitative structural study
      of lung and right ventricle outflow tract reconstruction in infants with
      tetralogy of Fallot. METHODS: Lung biopsies were taken during the operations in
      16 infants suffered from tetralogy of Fallot. Autopsy specimens were obtained
      from 5 infants died of non-cardiovascular diseases as normal control group. All
      patients underwent one staged repair. The techniques of right ventricular outflow
      tract reconstruction included pulmonary valve commissurotomy (n = 3), transanular
      pericardial patch (n = 4), and transannular homologous monocuspid valve patch (n
      = 8); homograft was used in one patient because of the abnormal coronary artery.
      The diameters of main pulmonary artery (MPA), left pulmonary artery (LPA), and
      right pulmonary artery (RPA) were measured during operation. The tissue was fixed
      with buffered formalin and routinely impregnated in wax. Sections were stained by
      hematoxylin-eosin, and Weigert's elastic stain counter-stained by van Gieoson's
      method. Seven parameters of the small pulmonary arteries were obtained, including
      percentage of media thickness (% MT), percentage of media section area (% MS),
      numbers of pulmonary small artery per square centimeter (APSC), mean alveolar
      number (MAN), mean linear intercept (MLI), proportion of parenchyma area in total
      area (% PPA), and alveolar/ small arterial ratio per unit area (AAR) by a
      computer-based image processor for quantitative analysis. RESULTS: In the TOF
      group, % MT, % MS, and APSC significantly decreased, while MLI and AAR
      significantly increased (P < 0.05, compared with the control group). APSC
      decreased in turn after separately using three different techniques of right
      ventricular outflow tract reconstruction (i. e. pulmonary valve commissurotomy,
      transannular pericardium patch, and transannular homologous monocuspid valve
      patch), which was paralleled with the diameters of MPA, LPA, and RPA. RPA
      correlated with APSC (r = 0.754, P = 0.001). CONCLUSIONS: The development of
      pulmonary small arteries and alveoli are directly affected by the diminished
      pulmonary flow in infants with tetralogy of Fallot. Right ventricle outflow tract
      reconstruction may be indicated according to the developmental degree of central
      pulmonary artery.

PMID- 16900645
TI  - [Comparison of hemodynamic responses to orotracheal intubation between using
      GlideScope videolaryngoscope and fiberoptic bronchoscope].
AB  - OBJECTIVE: To compare the hemodynamic responses to orotracheal intubation with
      GlideScope videolaryngoscope (GSVL) and with fiberoptic bronchoscope (FOB) after
      induction of general anesthesia. METHODS: Totally 57 ASA physical status I - II
      adult patients undergoing elective plastic surgery and requiring orotracheal
      intubation were randomly allocated to either GSVL group (n = 29) or FOB group (n
      = 28). After a routine intravenous anesthetic induction, orotracheal intubation
      was performed. Noninvasive blood pressure (BP) and heart rate (HR) were recorded
      before and after anesthetic induction, at intubation and thereafter at 1 minute
      interval for 5 minutes. RESULTS: The intubation time was not significantly
      different between the two groups (P > 0.05). After intubation, BP and HR
      exhibited significant increases compared to the post-induction values in both
      groups, but the maximum values of BP did not exceed the pre-induction values
      while the maximum value of HR was higher than the pre-induction value. During the
      observation, BP and HR at all time points as well as the maximum values of BP and
      HR had no significant differences between the two groups (P > 0.05). CONCLUSION:
      The orotracheal intubations using FOB and GSVL result in similar hemodynamic
      responses.

PMID- 16900646
TI  - [Diagnosis and treatment of chronic lymphocytic thyroiditis coexistent with
      thyroid malignancy].
AB  - OBJECTIVE: To explore the principles of diagnosis and treatment of chronic
      lymphocytic thyroiditis (CLT) coexistent with thyroid malignancy. METHODS: The
      clinical data of 52 patients with CLT, including clinicopathologic features,
      treatment, and prognosis were retrospectively analyzed. Among these 52 patients,
      40 patients had coexisting thyroid carcinoma (TC group) and 12 had coexisting
      thyroid lymphoma (TL group). RESULTS: These two thyroid malignancies accounted
      for 13.87% of all the CLT inpatients during this period, in which 10.67% were CLT
      with carcinoma and 3.20% were CLT with lymphoma. Significant differences existed
      between TC group and TL group in sex (P = 0.008) , age (P = 0.000), and B-mode
      ultrasound findings (P = 0.000). Most patients in TC group received total
      lobectomy of one lobe and subtotal lobectomy of the other side, of which some
      received elective lymphadenectomy. The operations varied among patients in TL
      group, and most of them received chemotherapy after surgery. The median follow-up
      was (35.51 +/- 39.84) months for 37 patients in TC group, and 36 patients
      survived with a median period of (34.50 +/- 39.91) months; the median follow-up
      was (39.50 +/- 29.00) months for 12 patients in TL group, and 10 patients
      survived with a median period of (44.70 +/- 28.78) months. CONCLUSIONS: CLT with
      thyroid malignancies are not uncommon in clinical practice. While thyroid
      carcinoma accounts for majority of these malignancies, its clinicopathologic
      features, treatment, and prognosis differs with thyroid lymphoma. Surgery may be
      appropriate for CLT patients with rapid thyroid enlargement or nodule, and for
      patients with solitary solid nodule or nodules with calcification revealed by B
      ultrasound.

PMID- 16900647
TI  - [Factors influencing the recurrence of Cushing's disease treated by
      transsphenoidal surgery].
AB  - OBJECTIVE: To explore factors influencing the recurrence of patients with
      Cushing's disease after transsphenoidal surgery. METHODS: We retrospectively
      analyzed the clinical data of 182 patients treated by transsphenoidal surgery
      with Cushing's disease in our department in PUMC Hospital from 1992 to 2002.
      RESULTS: The recurrence rates were significantly different when patients had
      different radiological findings (P = 0.001), operative methods (P = 0.001),
      histological findings (P = 0.04), and postoperative cortisol levels (P = 0.02);
      however, such difference was not found in term of tumor size (P = 0.43).
      CONCLUSION: Radiological findings, operative methods, histological findings, and
      postoperative cortisol estimates may be the factors influencing the recurrence of
      patients treated by transsphenoidal surgery.

PMID- 16900648
TI  - [Clinicopathological features of solid pseudopapillary tumor of the pancreas].
AB  - OBJECTIVE: To elucidate the clinicopathological features of solid pseudopapillary
      tumor (SPT) of the pancreas. METHODS: Eight patients with SPT of the pancreas
      admitted from August 1996 to March 2005 were retrospectively analyzed. RESULTS:
      All the 8 patients were female with an average age of 25.3 (13-41) years. The
      primary clinical manifestations included abdominal mass (n = 3), vague abdominal
      pain (n = 3), and duodenal obstruction (n = 1). SPT was occasionally found in one
      patient during physical examination. Six tumors located at the head and the other
      two in the body and tail of the pancreas. Pancreaticoduodenectomies were
      performed in 4 patients, tumor enucleations in 2, distal pancreatectomies in 1,
      and palliative internal drainage with a cystoenterotomy in the other one with an
      unresectable huge cystic lesion. All patients were alive on an average follow-up
      of 37.8 (8-103) months. CONCLUSION: SPT occurs mainly in adolescent and young
      females, and satisfactory outcome may be achieved with active and appropriate
      surgeries.

PMID- 16900650
TI  - [Clinical application of PET and PET/CT in radiotherapy of head and neck cancer].
AB  - Positron emission tomography (PET) is a functional imaging modality. The combined
      PET and CT scan provides more accurate detection of tumors and their relationship
      with normal tissues by providing the functional and anatomic information
      simultaneously. Relevant researches have been focused on the application of
      combined PET/CT in the radiotherapy of head and neck cancer, which includes:
      providing valuable information in the staging of head and neck cancer before
      radiotherapy; localizing a primary tumor in patients with unknown metastases in
      cervical lymph nodes; predicting the response of tumors to radiotherapy;
      providing biological target volume to radiation treatment planning, especially in
      intensity-modulated radiotherapy; and monitoring the residual and recurrent
      diseases after radiotherapy. However, its application in many aspects is still
      controversy, and further researches in its clinical application are still needed.

PMID- 16900649
TI  - [Effects of long-term and low-dose hormone replacement therapy on bone mineral
      density in postmenopausal women].
AB  - OBJECTIVE: To observe the effects of long-term and low-dose hormone replacement
      therapy on bone mineral density (BMD), and the incidence of bone pain in
      postmenopausal women. METHODS: Totally 141 postmenopausal women were selected
      from the medical staff of the Peking Union Medical College Hospital. Of them, 63
      women treated with low-dose sex hormone for over 5 (5-32) years were divided into
      hormone replacement therapy (HRT) group, and 78 never receiving HRT were divided
      into control group. The BMD was measured by dual energy X-ray absorptiometry
      (DEXA) at lumbar spine, Ward's triangle, femoral neck, trochanter, and total hip,
      and the incidence of bone pain was inquired. RESULTS: The BMD in the HRT group
      was 9.1% higher than that in the control group (P < 0.05). The incidence of bone
      pain was significantly lower in the HRT group (71.4%) than that in the control
      group (89.7%). CONCLUSION: Long-term and low-dose hormone replacement therapy can
      reduce bone loss and the incidence of bone pain.

PMID- 16900651
TI  - [Current opinions in therapeutics of advanced laryngeal carcinoma].
AB  - The treatment of advanced laryngeal cancer constitutes a constant challenge to
      surgeons. Although various therapeutic modalities have been employed in the past
      century, the cure rate remains unsatisfactory. Current opinions in the
      therapeutics of this disease pay more attention to the preservation of larynx
      function and the improvement of quality of life. It is practical to improve the
      survival rate and quality of life by upgrading the conservative surgical
      techniques and radiotherapy tactics, neo-adjuvant therapies, and especially the
      combined treatment using concurrent chemoradiotherapy.

PMID- 16900652
TI  - [Monoclonal antibodies in the treatment of malignant lymphoma].
AB  - Monoclonal antibodies (MoAbs) have different mechanism and adverse effects
      compared with cytotoxic agents. The introduction of MoAbs has improved the
      treatment potency to malignant lymphoma without decreasing the quality of life.
      However, there are many questions to be answered: What is the profound mechanism
      of MoAbs? How about their long-term adverse effects? What is the best medication
      pattern in different disease types?

PMID- 16900653
TI  - [Itraconazole in the treatment of superficial candidal infections: twelve years'
      clinical experience].
AB  - Itraconazole has been used to treat superficial candidal infections in China for
      12 years with promising efficacy and safety. This article retrospectively
      reviewed literatures published in the mainstream journals in China with an
      attempt to find a reasonable therapy for Chinese populations.

PMID- 16900654
TI  - [Application of imiquimod and resiquimod in dermatology].
AB  - Imiquimod (R-837) and Resiquimod (R-838), two novel small-molecular-weight immune
      response modifiers, have similar structure. They have anti-virus and anti-tumor
      activities and can be used as B lymphocyte activators and adjuvants. They are
      widely used in dermatology to treat virus dermatoses and cutaneous benign or
      malignant tumors.

PMID- 16900655
TI  - [Immunoregulatory effects of mesenchymal stem cell and its application].
AB  - The immunoregulatory effects of mescenchymal stem cell (MSC) and its application
      have become a hot research topic in recent years. This article reviews the up-to
      dated research advances in the features and mechanisms of immune regulation of
      MSC and its application.

PMID- 16900656
TI  - [Primary agiitis of central nervous system].
AB  - The common clinical manifestations of the primary agiitis of the central nervous
      system include burst of headache, dementia, change of aptitude, paralysis of
      cranial nerves, and recurrent focal depletion of the neural function.
      Lptomeningeal and brain biopsy are still the gold criteria for diagnosis. The
      prognosis may be improved after cortin and immunosuppressant therapy.

PMID- 16900657
TI  - [Endovenous laser combined with ligation and striping therapy for varicose
      saphenous].
AB  - OBJECTIVE: To evaluate the curative effect of the combination of endovenous laser
      treatment of varicose saphenous vein (ELVS) and classic ligation and stripping
      treatment. METHODS: We retrospectively analyzed the clinical data of 21 patients
      with varicose saphenous vein (VS) who were treated with ELVS alone or combined
      with ligation and stripping in our hospital. RESULTS: All the patients got good
      therapy result. The early symptom relief rate was 82.4%, while the late symptom
      relief rate was 100%. No infections, haematoma of wound, and any other major
      complications were reported. The common complications included pain induced by
      remains of the thrombosis phlebitis (n = 2, 11.7%), minor skin burn (n = 1,
      5.9%), residue vein varicose (n = 1, 5.9%), numbness of the calf (n = 1, 5.9%),
      and mild peri-phlebitis (n = 1, 5.9%). All the complications were resolved after
      proper management. The 1-year follow-up showed no recurrence. CONCLUSION: The
      combination of ELVS and classic ligation and stripping is safe and effective in
      the treatment of varicose saphenous.

PMID- 16900658
TI  - [Caesarean sections performed under general anesthesia].
AB  - OBJECTIVE: To analyse the preoperative conditions and intraoperative anesthetic
      managements of parturients who underwent Caesarean section and explore possible
      relationship between perianesthetic managements and prognosis of parturients and
      fetuses. METHODS: A group of 30 parturients who underwent Caesarean sections
      under general anesthesia were analysed retrospectively. RESULTS: All the 30
      Caesarean sections were smooth in terms of both procedure and anesthesia.
      CONCLUSIONS: General anesthesia is still indicated in Caesarean section, although
      multiple risks may still exist. Considerate perinatal planning, careful
      preoperative preparations, and delicate intraoperative managements positively
      contribute to the good prognosis of parturient and fetus.

PMID- 16900659
TI  - Antiestrogenic therapies in solid cancers and multiple myeloma.
AB  - Estrogens are essential for human health. Their physiological effects are
      primarily mediated by two types of intracellular estrogen receptors (ER alpha and
      ER beta) that function as DNA-binding transcription factors. However, estrogens
      are also involved in the development and progression of breast cancers. Endocrine
      therapy aims to reduce the availability of the hormone or to counteract its
      action. This can be achieved by preventing estrogen production or administrating
      antiestrogens (AEs), synthetic drugs belonging to several distinct structural
      categories. Selective estrogen receptor modulators (or SERMs) bind ERs but have a
      mixed agonist/antagonist profile. Selective estrogen receptor downregulators (or
      SERDs) are pure antiestrogens, acting by decreasing the level of ERs through
      their ubiquitinylation and subsequent targeting to the proteasome. We review most
      of the usual antiestrogenic therapies for estrogen-dependent and estrogen
      independent solid cancers and present our recent results on the use of AEs
      against multiple myeloma. In breast cancer treatments, the most commonly used
      antiestrogen, tamoxifen, has major limitations: side effects due to its partial
      agonist activity and constitutive or acquired resistance. We propose that novel
      AE drug delivery systems may enhance the overall beneficial effects by targeting
      tumoral cells.

PMID- 16900660
TI  - Islet cell transplantation.
AB  - Islet cell transplantation is an attractive alternative therapy to conventional
      insulin treatment or vascularized whole pancreas transplantation for type 1
      diabetic patients. It represents a successful example of somatic cell therapy in
      humans based on complex procedures for islet isolation from whole pancreas. The
      islets, that are only 1% of the total pancreas tissue, are isolated by two steps
      method starting with collagenase digestion that operates a rapid dissociation of
      the stromal component of the gland, while preserving islet anatomical integrity.
      After digestion, islets are then separated from exocrine tissue by centrifugation
      in density gradients. Transplantation consists of a simple injection of few
      milliliter-purified tissue in the portal vein through a percutaneous trans
      hepatic approach performed in local anesthesia. Several studies have now
      demonstrated that islet transplant can replace pancreatic endocrine function
      without major side effects and with liver viability preservation in selected
      patients affected by long-term type 1 diabetes. It can restore endogenous insulin
      secretion, achieve insulin independence in more than 80% of patients, and recover
      the metabolism of glucose, protein and lipids. Improved control of glycated
      HbA1c, reduced risk of recurrent hypoglycemia and of diabetic complications are
      also seen as important benefits of islet cell transplantation, irrespective of
      the status of insulin independence. Many protocols are now on going for reduction
      of immunosuppression therapy in recipients, induction of tolerance, and
      prolongation of graft function.

PMID- 16900661
TI  - Apoptosis in physiological and pathological skin: implications for therapy.
AB  - Apoptosis is an inducible suicide program that occurs in all phases of
      multicellular as well as in protozoa life and gains more and more importance in
      all medical disciplines. It is required for normal ontogenesis, organ and tissue
      remodeling, function of the immune system, prevention of inappropriate cellular
      proliferation and of survival of inappropriate mutations. Thereby apoptosis
      represents the key event which guarantees differentiation and maintenance of
      homeostasis. Terminal differentiation seems to be a special form of apoptosis.
      Dysregulated apoptosis is associated with various pathological conditions,
      including inflammation, and cancer. Acanthosis, the hallmark of psoriatic skin,
      is an example for diminished epidermal apoptosis. Defects in termination of
      inflammatory reactions occur in atopic dermatitis. Lupus erythematosus may arise
      due to disturbed apoptosis on several check points of the apoptosis cascade.
      Experimental evidence suggests a role for Bcl-2 and CD95L in the inhibition of
      programmed cell death in UV-induced skin cancer or malignant melanoma cells.
      Thus, it leads to survival of malignant cell clones. The slow growth of basal
      cell carcinomas is due to an increased apoptosis to mitosis ratio. Spontaneous
      regression of tumors is associated with increased apoptotic rates. Malignant
      melanoma cells characteristically show different anti-apoptotic strategies which
      underscore its aggressive behavior and its refractory towards classic therapeutic
      regimens. Additionally, induction of apoptosis in tumor infiltrating immune cells
      seems to be a strategy by which the tumor escapes from an immunological attack
      (tumor counter-attack). Since apoptosis is either absent or altered under
      pathological conditions therapeutic procedures should correct this. Established
      therapies like dithranol, vitanin-D3 analogs, low-dose methotrexate, induce
      apoptosis. Future treatment regimens like vaccine and gene therapy are designed
      to selectively induce apoptosis. Therefore, pharmacological agents and
      therapeutic strategies interfering with disrupted apoptosis regulation could
      improve the therapeutic arsenal in the future.

PMID- 16900662
TI  - Bone diseases associated with human immunodeficiency virus infection:
      pathogenesis, risk factors and clinical management.
AB  - Bone disorders such as osteopenia and osteoporosis have been recently reported in
      patients infected with the human immunodeficiency virus (HIV), but their etiology
      remains still unknown. The prevalence estimates vary widely among the different
      studies and can be affected by concomitant factors such as the overlapping of
      other possible conditions inducing bone loss as lypodystrophy, advanced HIV
      disease, advanced age, low body weight or concomitant use of other drugs. All the
      reports at the moment available in the literature showed a higher than expected
      prevalence of reduced bone mineral density (BMD) in HIV-infected subjects both
      naive and receiving potent antiretroviral therapy compared to healthy controls.
      This controversial can suggest a double role played by both antiretroviral drugs
      and HIV itself due to immune activation and/or cytokines disregulation. An
      improved understanding of the pathogenesis of bone disorders can result in better
      preventative and therapeutic measures. However, the clinical relevance and the
      risk of fractures remains undefined in HIV-population. The clinical management of
      osteopenia and osteoporosis in HIV-infected subjects is still being evaluated.
      Addressing potential underlying bone disease risk factors (e.g., smoking and
      alcohol intake, use of corticosteroids, advanced age, low body weight),
      evaluating calcium and vitamin D intake, and performing dual x-ray absorptiometry
      in HIV-infected individuals who have risk factors for bone disease can be
      important strategies to prevent osteopenia and osteoporosis in this population.
      The administration of bisphosphonates (e.g., alendronate), with calcium and
      vitamin D supplementation, may be a reasonable and effective option to treat
      osteoporosis in these subjects.

PMID- 16900663
TI  - CpG island methylation in precursors of gastrointestinal malignancies.
AB  - Gastrointestinal malignancies account for about 20% of all cancers worldwide. It
      is widely accepted that cancer evolves through several stepwise morphological
      stages such as the adenoma-carcinoma and hyperplastic polyp-serrated adenoma
      carcinoma sequences in colorectal cancers, and the metaplasia-dysplasia-carcinoma
      sequences in esophageal and gastric cancers. The morphological progression is
      associated with the accumulation of multiple genetic and epigenetic events. It is
      now recognized that epigenetic silencing of gene expression by CpG island
      methylation is an important alternative mechanism of inactivating tumor
      suppressor genes. Inflammatory conditions of the gastrointestinal and
      pancreaticobiliary tracts and liver such as Barrett esophagus, Helicobacter
      pylori gastritis, inflammatory bowel disease and viral hepatitis, are associated
      with increased frequency of malignancies and CpG methylation. In addition, CpG
      methylation is present in aberrant crypt foci and pancreatic intraepithelial
      neoplasia that are considered putative precursors of colon and pancreatic
      carcinomas, respectively. Understanding of these early genetic and epigenetic
      changes allows for the discoveries of potential screening, monitoring and
      therapeutic strategies. Targeting of the epigenetic changes that occur before the
      development of frank malignancy offers a potential chemopreventive strategy.

PMID- 16900664
TI  - EGF and PDGF receptor tyrosine kinases as therapeutic targets for chronic lung
      diseases.
AB  - Cell-surface receptor tyrosine kinases play pivotal roles in development, tissue
      repair, and normal cellular homeostasis. Aberrant expression or signaling
      patterns of these kinases has also been linked to the progression of a diversity
      of diseases, including cancer, atherosclerosis, asthma, and fibrosis. Two major
      families of receptor tyrosine kinases, the epidermal growth factor receptor
      (EGFR) and platelet-derived growth factor receptor (PDGFR) families, have
      received a great deal of attention as potential therapeutic targets for pulmonary
      diseases, as these receptors have been shown to play key roles in chronic tissue
      remodeling in asthma, bronchitis, and pulmonary fibrosis. The EGFR system on
      epithelial cells and underlying mesenchymal cells (fibroblasts, myofibroblasts,
      and smooth muscle cells) drives numerous phenotypic changes during the
      progression of these pulmonary diseases, including epithelial cell mucous cell
      metaplasia and mesenchymal cell hyperplasia, differentiation, and extracellular
      matrix production. The PDGFR system, located primarily on mesenchymal cells,
      transduces signals for cell survival, growth and chemotaxis. The variety of EGFR
      and PDGFR ligands produced by the airway epithelium or adjacent mesenchymal cells
      allows for intimate epithelial-mesenchymal cell communication. A full
      understanding of the complex mechanisms involving these receptors and ligands
      should lead to therapeutic strategies for the treatment of a wide range of
      fibroproliferative lung diseases.

PMID- 16900665
TI  - Acetylcholine receptors and tau phosphorylation.
AB  - Alzheimer's disease (AD) is characterized by the presence, in the brain of the
      patients, of two aberrant structures: intracellular neurofibrillary tangles
      (NFTs), containing an abnormal hyperphosphorylated form of tau protein, and
      extracellular senile plaques (SPs), mainly composed by fibrillar amyloid beta
      peptide. Another feature of AD is the neurodegeneration and dysfunction of basal
      forebrain cholinergic system. A possible connection among those AD
      characteristics could occur. Thus, the purpose of this short review is to
      summarize the involvement of nicotinic (nAChR) and muscarinic (mAChR) receptors
      on tau phosphorylation, in a direct way, or through the previous interaction of
      some of these receptors with amyloid beta. Several studies have demonstrated that
      nAChR activation results in a significantly increase of tau phosphorylation,
      whereas mAChR activation, may prevent tau phosphorylation.

PMID- 16900666
TI  - Alterations of biological features of the cerebellum in sudden perinatal and
      infant death.
AB  - This article intends to show how the cerebellum, a structure ordinarily not
      considered in mediating breathing or cardiovascular control, may play a critical
      role in compensatory responses particularly to hypoxic insults occurring pre
      and/or postnatally and thus may be involved in the sudden unexplained perinatal
      and infant death. Besides the ontogenesis of the cerebellar cortex in man, we
      reported alterations of biopathological features (neuronal immaturity, altered
      apoptotic programs, negative expression of somatostatin and EN2 gene, intense c
      fos expression positivity, astrogliosis) in the cortex and in the dentate nucleus
      of the 63% of sudden deaths, and only in 10% of the controls. The correlation of
      these results with the mother's smoking habit was highly significant. Therefore,
      we support the hypothesis, already expressed in previous studies on brainstem, of
      a close relation between maternal cigarette smoking and a wide range of morpho
      physiological defects of the brain, leading to unexplained sudden death in
      stillbirths, newborns, and Sudden Infant Death Syndrome (SIDS) victims.

PMID- 16900667
TI  - Face recognition using recursive Fisher linear discriminant.
AB  - Fisher linear discriminant (FLD) has recently emerged as a more efficient
      approach for extracting features for many pattern classification problems as
      compared to traditional principal component analysis. However, the constraint on
      the total number of features available from FLD has seriously limited its
      application to a large class of problems. In order to overcome this disadvantage,
      a recursive procedure of calculating the discriminant features is suggested in
      this paper. The new algorithm incorporates the same fundamental idea behind FLD
      of seeking the projection that best separates the data corresponding to different
      classes, while in contrast to FLD the number of features that may be derived is
      independent of the number of the classes to be recognized. Extensive experiments
      of comparing the new algorithm with the traditional approaches have been carried
      out on face recognition problem with the Yale database, in which the resulting
      improvement of the performances by the new feature extraction scheme is
      significant.

PMID- 16900668
TI  - Rate distortion optimal bit allocation methods for volumetric data using JPEG
      2000.
AB  - Computer modeling programs that generate three-dimensional (3-D) data on fine
      grids are capable of generating very large amounts of information. These data
      sets, as well as 3-D sensor/measured data sets, are prime candidates for the
      application of data compression algorithms. A very flexible and powerful
      compression algorithm for imagery data is the newly released JPEG 2000 standard.
      JPEG 2000 also has the capability to compress volumetric data, as described in
      Part 2 of the standard, by treating the 3-D data as separate slices. As a decoder
      standard, JPEG 2000 does not describe any specific method to allocate bits among
      the separate slices. This paper proposes two new bit allocation algorithms for
      accomplishing this task. The first procedure is rate distortion optimal (for mean
      squared error), and is conceptually similar to postcompression rate distortion
      optimization used for coding codeblocks within JPEG 2000. The disadvantage of
      this approach is its high computational complexity. The second bit allocation
      algorithm, here called the mixed model (MM) approach, mathematically models each
      slice's rate distortion curve using two distinct regions to get more accurate
      modeling at low bit rates. These two bit allocation algorithms are applied to a 3
      D Meteorological data set. Test results show that the MM approach gives
      distortion results that are nearly identical to the optimal approach, while
      significantly reducing computational complexity.

PMID- 16900669
TI  - Product code optimization for determinate state LDPC decoding in robust image
      transmission.
AB  - We propose a novel scheme for error-resilient image transmission. The proposed
      scheme employs a product coder consisting of low-density parity check (LDPC)
      codes and Reed-Solomon codes in order to deal effectively with bit errors. The
      efficiency of the proposed scheme is based on the exploitation of determinate
      symbols in Tanner graph decoding of LDPC codes and a novel product code
      optimization technique based on error estimation. Experimental evaluation
      demonstrates the superiority of the proposed system in comparison to recent state
      of-the-art techniques for image transmission.

PMID- 16900670
TI  - Context-based coding of bilevel images enhanced by digital straight line
      analysis.
AB  - A new efficient compression scheme for bilevel images containing locally straight
      edges is presented. This paper is especially focused on lossless (intra) coding
      of binary shapes for image and video objects, but other images with similar
      characteristics such as line drawings, layers of digital maps, or segmentation
      maps are also encoded efficiently. The algorithm is not targeted at document
      images with text, which can be coded efficiently with dictionary-based techniques
      as in JBIG2. The scheme is based on a local analysis of the digital straightness
      of the causal part of the object boundary, which is used in the context
      definition for arithmetic encoding. Tested on individual images of standard TV
      resolution binary shapes and the binary layers of a digital map, the proposed
      algorithm outperforms PWC, JBIG, JBIG2, and MPEG-4 CAE. On the binary shapes, the
      code lengths are reduced by 21%, 27%, 28%, and 41%, respectively. On the map
      layers, the reductions are 31%, 34%, 32%, and 64%, respectively. The algorithm is
      also more efficient on the test material than the state-of-the-art generic
      bilevel image coder free tree.

PMID- 16900671
TI  - Adaptive prediction trees for image compression.
AB  - This paper presents a complete general-purpose method for still-image compression
      called adaptive prediction trees. Efficient lossy and lossless compression of
      photographs, graphics, textual, and mixed images is achieved by ordering the data
      in a multicomponent binary pyramid, applying an empirically optimized nonlinear
      predictor, exploiting structural redundancies between color components, then
      coding with hex-trees and adaptive runlength/Huffman coders. Color palettization
      and order statistics prefiltering are applied adaptively as appropriate. Over a
      diverse image test set, the method outperforms standard lossless and lossy
      alternatives. The competing lossy alternatives use block transforms and wavelets
      in well-studied configurations. A major result of this paper is that predictive
      coding is a viable and sometimes preferable alternative to these methods.

PMID- 16900672
TI  - Joint demosaicing and denoising.
AB  - The output image of a digital camera is subject to a severe degradation due to
      noise in the image sensor. This paper proposes a novel technique to combine
      demosaicing and denoising procedures systematically into a single operation by
      exploiting their obvious similarities. We first design a filter as if we are
      optimally estimating a pixel value from a noisy single-color (sensor) image. With
      additional constraints, we show that the same filter coefficients are appropriate
      for color filter array interpolation (demosaicing) given noisy sensor data. The
      proposed technique can combine many existing denoising algorithms with the
      demosaicing operation. In this paper, a total least squares denoising method is
      used to demonstrate the concept. The algorithm is tested on color images with
      pseudorandom noise and on raw sensor data from a real CMOS digital camera that we
      calibrated. The experimental results confirm that the proposed method suppresses
      noise (CMOS/CCD image sensor noise model) while effectively interpolating the
      missing pixel components, demonstrating a significant improvement in image
      quality when compared to treating demosaicing and denoising problems
      independently.

PMID- 16900673
TI  - Joint source-channel coding for wireless object-based video communications
      utilizing data hiding.
AB  - In recent years, joint source-channel coding for multimedia communications has
      gained increased popularity. However, very limited work has been conducted to
      address the problem of joint source-channel coding for object-based video. In
      this paper, we propose a data hiding scheme that improves the error resilience of
      object-based video by adaptively embedding the shape and motion information into
      the texture data. Within a rate-distortion theoretical framework, the source
      coding, channel coding, data embedding, and decoder error concealment are jointly
      optimized based on knowledge of the transmission channel conditions. Our goal is
      to achieve the best video quality as expressed by the minimum total expected
      distortion. The optimization problem is solved using Lagrangian relaxation and
      dynamic programming. The performance of the proposed scheme is tested using
      simulations of a Rayleigh-fading wireless channel, and the algorithm is
      implemented based on the MPEG-4 verification model. Experimental results indicate
      that the proposed hybrid source-channel coding scheme significantly outperforms
      methods without data hiding or unequal error protection.

PMID- 16900674
TI  - Rate-distortion analysis of motion-compensated rate scalable video.
AB  - Generally speaking, rate scalable video systems today are evaluated
      operationally, meaning that the algorithm is implemented and the rate-distortion
      performance is evaluated for an example set of inputs. However, in these cases it
      is difficult to separate the artifacts caused by the compression algorithm and
      data set with general trends associated with scalability. In this paper, we
      derive and evaluate theoretical rate-distortion performance bounds for both
      layered and continuously rate scalable video compression algorithms which use a
      single motion-compensated prediction (MCP) loop. These bounds are derived using
      rate-distortion theory based on an optimum mean-square error (MSE) quantizer, and
      are thus applicable to all methods of intraframe encoding which use MSE as a
      distortion measure. By specifying translatory motion and using an approximation
      of the predicted error frame power spectral density, it is possible to derive
      parametric versions of the rate-distortion functions which are based solely on
      the input power spectral density and the accuracy of the motion-compensated
      prediction. The theory is applicable to systems which allow prediction drift,
      such as the data-partitioning and SNR-scalability schemes in MPEG-2, as well as
      those with zero prediction drift such as fine granularity scalability MPEG-4. For
      systems which allow prediction drift we show that optimum motion compensation is
      a sufficient condition for stability of the decoding system.

PMID- 16900675
TI  - Drift-resistant SNR scalable video coding.
AB  - We address the problem of enhancement layer drift estimation for fine granular
      scalable video. An optimal per-pixel drift estimation algorithm is introduced.
      The encoder assumes that there is some truncation of the enhancement layer, which
      does not allow the enhancement layer reference to be properly reconstructed, and
      the encoder recursively estimates the associated drift and chooses coding modes
      accordingly. The approach yields performance gains of about 1 dB across low to
      medium rates. In addition, we investigate dual frame prediction, for both base
      and enhancement layer, with pulsed-quality allocation in the base

PMID- 16900676
TI  - A signal processing approach to symmetry detection.
AB  - We present an algorithm that detects rotational and reflectional symmetries of
      two-dimensional objects. Both symmetry types are effectively detected and
      analyzed using the angular correlation (AC), which measures the correlation
      between images in the angular direction. The AC is accurately computed using the
      pseudopolar Fourier transform, which rapidly computes the Fourier transform of an
      image on a near-polar grid. We prove that the AC of symmetric images is a
      periodic signal whose frequency is related to the order of the symmetry. This
      frequency is recovered via spectrum estimation, which is a proven technique in
      signal processing with a variety of efficient solutions. We also provide a novel
      approach for finding the center of symmetry and demonstrate the applicability of
      our scheme to the analysis of real images.

PMID- 16900677
TI  - A multiscale expectation-maximization semisupervised classifier suitable for
      badly posed image classification.
AB  - This paper deals with the problem of badly posed image classification. Although
      underestimated in practice, bad-posedness is likely to affect many real-world
      image classification tasks, where reference samples are difficult to collect
      (e.g., in remote sensing (RS) image mapping) and/or spatial autocorrelation is
      relevant. In an image classification context affected by a lack of reference
      samples, an original inductive learning multiscale image classifier, termed
      multiscale semisupervised expectation maximization (MSEM), is proposed. The
      rationale behind MSEM is to combine useful complementary properties of two
      alternative data mapping procedures recently published outside of image
      processing literature, namely, the multiscale modified Pappas adaptive clustering
      (MPAC) algorithm and the sample-based semisupervised expectation maximization
      (SEM) classifier. To demonstrate its potential utility, MSEM is compared against
      nonstandard classifiers, such as MPAC, SEM and the single-scale contextual SEM
      (CSEM) classifier, besides against well-known standard classifiers in two RS
      image classification problems featuring few reference samples and modestly useful
      texture information. These experiments yield weak (subjective) but numerous
      quantitative map quality indexes that are consistent with both theoretical
      considerations and qualitative evaluations by expert photointerpreters. According
      to these quantitative results, MSEM is competitive in terms of overall image
      mapping performance at the cost of a computational overhead three to six times
      superior to that of its most interesting rival, SEM. More in general, our
      experiments confirm that, even if they rely on heavy class-conditional normal
      distribution assumptions that may not be true in many real-world problems (e.g.,
      in highly textured images), semisupervised classifiers based on the iterative
      expectation maximization Gaussian mixture model solution can be very powerful in
      practice when: 1) there is a lack of reference samples with respect to the
      problem/model complexity and 2) texture information is considered negligible
      (i.e., a piecewise constant image model holds).

PMID- 16900678
TI  - An edge-guided image interpolation algorithm via directional filtering and data
      fusion.
AB  - Preserving edge structures is a challenge to image interpolation algorithms that
      reconstruct a high-resolution image from a low-resolution counterpart. We propose
      a new edge-guided nonlinear interpolation technique through directional filtering
      and data fusion. For a pixel to be interpolated, two observation sets are defined
      in two orthogonal directions, and each set produces an estimate of the pixel
      value. These directional estimates, modeled as different noisy measurements of
      the missing pixel are fused by the linear minimum mean square-error estimation
      (LMMSE) technique into a more robust estimate, using the statistics of the two
      observation sets. We also present a simplified version of the LMMSE-based
      interpolation algorithm to reduce computational cost without sacrificing much the
      interpolation performance. Experiments show that the new interpolation techniques
      can preserve edge sharpness and reduce ringing artifacts.

PMID- 16900679
TI  - Superresolution and noise filtering using moving least squares.
AB  - An irregularly spaced sampling raster formed from a sequence of low-resolution
      frames is the input to an image sequence superresolution algorithm whose output
      is the set of image intensity values at the desired high-resolution image grid.
      The method of moving least squares (MLS) in polynomial space has proved to be
      useful in filtering the noise and approximating scattered data by minimizing a
      weighted mean-square error norm, but introducing blur in the process. Starting
      with the continuous version of the MLS, an explicit expression for the filter
      bandwidth is obtained as a function of the polynomial order of approximation and
      the standard deviation (scale) of the Gaussian weight function. A discrete
      implementation of the MLS is performed on images and the effect of choice of the
      two dependent parameters, scale and order, on noise filtering and reduction of
      blur introduced during the MLS process is studied.

PMID- 16900680
TI  - Geodesic matching of triangulated surfaces.
AB  - Recognition of images and shapes has long been the central theme of computer
      vision. Its importance is increasing rapidly in the field of computer graphics
      and multimedia communication because it is difficult to process information
      efficiently without its recognition. In this paper, we propose a new approach for
      object matching based on a global geodesic measure. The key idea behind our
      methodology is to represent an object by a probabilistic shape descriptor that
      measures the global geodesic distance between two arbitrary points on the surface
      of an object. In contrast to the Euclidean distance which is more suitable for
      linear spaces, the geodesic distance has the advantage to be able to capture the
      intrinsic geometric structure of the data. The matching task therefore becomes a
      one-dimensional comparison problem between probability distributions which is
      clearly much simpler than comparing three-dimensional structures. Object matching
      can then be carried out by an information-theoretic dissimilarity measure
      calculations between geodesic shape distributions, and is additionally
      computationally efficient and inexpensive.

PMID- 16900681
TI  - High-throughput analysis of multispectral images of breast cancer tissue.
AB  - Statistical analysis of genetic changes within cell nuclei that are far from the
      primary tumor would help determine whether such changes have occurred prior to
      tumor invasion. To determine whether the gene amplification in cells is
      morphologically and/or genetically related to the primary tumor requires
      quantitative evaluation of a large number of cell nuclei from continuous
      meaningful structures such as milk-ducts, tumors, etc., located relatively far
      from the primary tumor. To address this issue, we have designed an integrated
      image analysis software system for high-throughput segmentation of nuclei.
      Filters such as Beltrami flow-based reaction-diffusion, directional diffusion,
      etc., were used to pre-process the images resulting in a better segmentation. The
      accurate shape of the segmented nucleus was recovered using an iterative "shrink
      wrap" operation. The study of two cases of ductal carcinoma in situ in breast
      tissue supports the biological observation regarding the existence of a
      preferential intraductal invasion, and therefore a common origin, between the
      primary tumor and the gene amplification in the cell-nuclei lining the ductal
      structures in the breast.

PMID- 16900682
TI  - Estimation of optimal PDE-based denoising in the SNR sense.
AB  - This paper is concerned with finding the best partial differential equation-based
      denoising process, out of a set of possible ones. We focus on either finding the
      proper weight of the fidelity term in the energy minimization formulation or on
      determining the optimal stopping time of a nonlinear diffusion process. A
      necessary condition for achieving maximal SNR is stated, based on the covariance
      of the noise and the residual part. We provide two practical alternatives for
      estimating this condition by observing that the filtering of the image and the
      noise can be approximated by a decoupling technique, with respect to the weight
      or time parameters. Our automatic algorithm obtains quite accurate results on a
      variety of synthetic and natural images, including piecewise smooth and textured
      ones. We assume that the statistics of the noise were previously estimated. No a
      priori knowledge regarding the characteristics of the clean image is required. A
      theoretical analysis is carried out, where several SNR performance bounds are
      established for the optimal strategy and for a widely used method, wherein the
      variance of the residual part equals the variance of the noise.

PMID- 16900684
TI  - Gray-level grouping (GLG): an automatic method for optimized image contrast
      enhancement--Part I: the basic method.
AB  - Contrast enhancement has an important role in image processing applications.
      Conventional contrast enhancement techniques either often fail to produce
      satisfactory results for a broad variety of low-contrast images, or cannot be
      automatically applied to different images, because their parameters must be
      specified manually to produce a satisfactory result for a given image. This paper
      describes a new automatic method for contrast enhancement. The basic procedure is
      to first group the histogram components of a low-contrast image into a proper
      number of bins according to a selected criterion, then redistribute these bins
      uniformly over the grayscale, and finally ungroup the previously grouped gray
      levels. Accordingly, this new technique is named gray-level grouping (GLG). GLG
      not only produces results superior to conventional contrast enhancement
      techniques, but is also fully automatic in most circumstances, and is applicable
      to a broad variety of images. An extension of GLG, selective GLG (SGLG), and its
      variations will be discussed in Part II of this paper. SGLG selectively groups
      and ungroups histogram components to achieve specific application purposes, such
      as eliminating background noise, enhancing a specific segment of the histogram,
      and so on. The extension of GLG to color images will also be discussed in Part
      II.

PMID- 16900683
TI  - Variational denoising of partly textured images by spatially varying constraints.
AB  - Denoising algorithms based on gradient dependent regularizers, such as nonlinear
      diffusion processes and total variation denoising, modify images towards
      piecewise constant functions. Although edge sharpness and location is well
      preserved, important information, encoded in image features like textures or
      certain details, is often compromised in the process of denoising. We propose a
      mechanism that better preserves fine scale features in such denoising processes.
      A basic pyramidal structure-texture decomposition of images is presented and
      analyzed. A first level of this pyramid is used to isolate the noise and the
      relevant texture components in order to compute spatially varying constraints
      based on local variance measures. A variational formulation with a spatially
      varying fidelity term controls the extent of denoising over image regions. Our
      results show visual improvement as well as an increase in the signal-to-noise
      ratio over scalar fidelity term processes. This type of processing can be used
      for a variety of tasks in partial differential equation-based image processing
      and computer vision, and is stable and meaningful from a mathematical viewpoint.

PMID- 16900685
TI  - Gray-level grouping (GLG): an automatic method for optimized image contrast
      enhancement--Part II: the variations.
AB  - This is Part II of the paper, "Gray-Level Grouping (GLG): an Automatic Method for
      Optimized Image Contrast Enhancement". Part I of this paper introduced a new
      automatic contrast enhancement technique: gray-level grouping (GLG). GLG is a
      general and powerful technique, which can be conveniently applied to a broad
      variety of low-contrast images and outperforms conventional contrast enhancement
      techniques. However, the basic GLG method still has limitations and cannot
      enhance certain classes of low-contrast images well, e.g., images with a noisy
      background. The basic GLG also cannot fulfill certain special application
      purposes, e.g., enhancing only part of an image which corresponds to a certain
      segment of the image histogram. In order to break through these limitations, this
      paper introduces an extension of the basic GLG algorithm, selective gray-level
      grouping (SGLG), which groups the histogram components in different segments of
      the grayscale using different criteria and, hence, is able to enhance different
      parts of the histogram to various extents. This paper also introduces two new
      preprocessing methods to eliminate background noise in noisy low-contrast images
      so that such images can be properly enhanced by the (S)GLG technique. The
      extension of (S)GLG to color images is also discussed in this paper. SGLG and its
      variations extend the capability of the basic GLG to a larger variety of low
      contrast images, and can fulfill special application requirements. SGLG and its
      variations not only produce results superior to conventional contrast enhancement
      techniques, but are also fully automatic under most circumstances, and are
      applicable to a broad variety of images.

PMID- 16900686
TI  - Edge-forming methods for color image zooming.
AB  - This paper introduces edge-forming schemes for image zooming of color images by
      general magnification factors. In order to remove/reduce artifacts arising in
      image interpolation, such as image blur and the checkerboard effect, an edge
      forming method is suggested to be applied as a postprocess of standard
      interpolation methods. The method is based on nonconvex nonlinear partial
      differential equations. The equations are carefully discretized, incorporating
      numerical schemes of anisotropic diffusion, to be able to form reliable edges
      satisfactorily. The alternating direction implicit (ADI) method is employed for
      an efficient simulation of the model. It has been numerically verified that the
      resulting algorithm can form clear edges in 2 to 3 ADI iterations. Various
      results are given to show th eeffectiveness and reliability of the algorithm.

PMID- 16900687
TI  - Partition-based vector filtering technique for suppression of noise in digital
      color images.
AB  - A partition-based adaptive vector filter is proposed for the restoration of
      corrupted digital color images. The novelty of the filter lies in its unique
      three-stage adaptive estimation. The local image structure is first estimated by
      a series of center-weighted reference filters. Then the distances between the
      observed central pixel and estimated references are utilized to classify the
      local inputs into one of preset structure partition cells. Finally, a weighted
      filtering operation, indexed by the partition cell, is applied to the estimated
      references in order to restore the central pixel value. The weighted filtering
      operation is optimized off-line for each partition cell to achieve the best
      tradeoff between noise suppression and structure preservation. Recursive
      filtering operation and recursive weight training are also investigated to
      further boost the restoration performance. The proposed filter has demonstrated
      satisfactory results in suppressing many distinct types of noise in natural color
      images. Noticeable performance gains are demonstrated over other prior-art
      methods in terms of standard objective measurements, the visual image quality and
      the computational complexity.

PMID- 16900688
TI  - Image registration using the Walsh transform.
AB  - This paper presents a new algorithm which can be used to register images of the
      same or different modalities, e.g., images with multiple channels, such as X
      rays, temperature or elevation, or simply images of different spectral bands. In
      particular, a correlation-based scheme is used, but instead of gray values, it
      correlates numbers formulated by different combinations of the extracted local
      Walsh coefficients of the images. Each image patch is expanded in terms of Walsh
      basis functions. Each Walsh basis function can be thought of as measuring a
      different aspect of local structure, e.g., horizontal edge, corner, etc. The
      coefficients of the expansion, therefore, can be thought of as dense local
      features, estimating at each point the degree of presence of, for example, a
      horizontal edge, a corner with contrast of a certain type, etc. These
      coefficients are normalized and used as digits in a chosen number system which
      allows one to create a unique number for each type of local structure. The choice
      of the basis of the number system allows one to give different emphasis to
      different types of local feature (e.g., corners versus edges), and, thus, the
      method we present forms a unified framework in terms of which several feature
      matching methods may be interpreted. The algorithm is compared with wavelet and
      contour based approaches, using simulated and real images. The two images are
      assumed to differ from each other by a rotation and a translation only.

PMID- 16900689
TI  - A measure for mutual refinements of image segmentations.
AB  - In this paper, we recover a graph interpretation of the mutual partition
      distance, proposed recently by Cardoso and Corte-Real. We deduce some properties
      of this measure, and establish a correspondence with the partition distance
      introduced by Almudevar and Field and Gusfield, and independently by Guigues. We
      also present some different formulations for the computation of the mutual
      partition distance. Finally, a comparison is made with similar measures.

PMID- 16900690
TI  - Vehicle detection by means of stereo vision-based obstacles features extraction
      and monocular pattern analysis.
AB  - This paper presents a stereo vision system for the detection and distance
      computation of a preceding vehicle. It is divided in two major steps. Initially,
      a stereo vision-based algorithm is used to extract relevant three-dimensional (3
      D) features in the scene, these features are investigated further in order to
      select the ones that belong to vertical objects only and not to the road or
      background. These 3-D vertical features are then used as a starting point for
      preceding vehicle detection; by using a symmetry operator, a match against a
      simplified model of a rear vehicle's shape is performed using a monocular vision
      based approach that allows the identification of a preceding vehicle. In
      addition, using the 3-D information previously extracted, an accurate distance
      computation is performed.

PMID- 16900691
TI  - Using the low-resolution properties of correlated images to improve the
      computational efficiency of eigenspace decomposition.
AB  - Eigendecomposition is a common technique that is performed on sets of correlated
      images in a number of computer vision and robotics applications. Unfortunately,
      the computation of an eigendecomposition can become prohibitively expensive when
      dealing with very high-resolution images. While reducing the resolution of the
      images will reduce the computational expense, it is not known a priori how this
      will affect the quality of the resulting eigendecomposition. The work presented
      here provides an analysis of how different resolution reduction techniques affect
      the eigendecomposition. A computationally efficient algorithm for calculating the
      eigendecomposition based on this analysis is proposed. Examples show that this
      algorithm performs well on arbitrary video sequences.

PMID- 16900692
TI  - Fast point-based 3-D alignment of live cells.
AB  - Typical time intervals between acquisitions of three-dimensional (3-D) images of
      the same cell in live cell imaging are in the orders of minutes. In the meantime,
      the live cell can move in a water basin on the stage. This movement can hamper
      the studies of intranuclear processes. We propose a fast point-based image
      registration method for the suppression of the movement of a cell as a whole in
      the image data. First, centroids of certain intracellular objects are computed
      for each image in a time-lapse series. Then, a matching between the centroids,
      which have the maximal number of pairs, is sought between consecutive point sets
      by a 3-D extension of a two-dimensional fast point pattern matching method, which
      is invariant to rotation, translation, local distortion, and extra/missing
      points. The proposed 3-D extension assumes rotations only around the z axis to
      retain the complexity of the original method. The final step involves computing
      the optimal fully 3-D transformation between images from corresponding points in
      the least-squares manner. The robustness of the method was evaluated on generated
      data. The results of the simulations show that the method is very precise and its
      correctness can be estimated. This article also presents two practical
      application examples, namely the registration of images of HP1 domains and the
      registration of images of telomeres. More than 97% of time-consecutive images
      were successfully registered. The results show that the method is very well
      suited to live cell imaging.

PMID- 16900693
TI  - Image analysis using a dual-tree M-band wavelet transform.
AB  - We propose a two-dimensional generalization to the M-band case of the dual-tree
      decomposition structure (initially proposed by Kingsbury and further investigated
      by Selesnick) based on a Hilbert pair of wavelets. We particularly address: 1)
      the construction of the dual basis and 2) the resulting directional analysis. We
      also revisit the necessary pre-processing stage in the M-band case. While several
      reconstructions are possible because of the redundancy of the representation, we
      propose a new optimal signal reconstruction technique, which minimizes potential
      estimation errors. The effectiveness of the proposed M-band decomposition is
      demonstrated via denoising comparisons on several image types (natural, texture,
      seismics), with various M-band wavelets and thresholding strategies. Significant
      improvements in terms of both overall noise reduction and direction preservation
      are observed.

PMID- 16900694
TI  - Curved wavelet transform for image coding.
AB  - The conventional two-dimensional wavelet transform used in existing image coders
      is usually performed through one-dimensional (1-D) filtering in the vertical and
      horizontal directions, which cannot efficiently represent edges and lines in
      images. The curved wavelet transform presented in this paper is carried out by
      applying 1-D filters along curves, rather than being restricted to vertical and
      horizontal straight lines. The curves are determined based on image content and
      are usually parallel to edges and lines in the image to be coded. The pixels
      along these curves can be well represented by a small number of wavelet
      coefficients. The curved wavelet transform is used to construct a new image
      coder. The code-stream syntax of the new coder is the same as that of JPEG2000,
      except that a new marker segment is added to the tile headers. Results of image
      coding and subjective quality assessment show that the new image coder performs
      better than, or as well as, JPEG2000. It is particularly efficient for images
      that contain sharp edges and can provide a PSNR gain of up to 1.67 dB for natural
      images compared with JPEG2000.

PMID- 16900695
TI  - Fast vector quantization algorithms based on nearest partition set search.
AB  - A fast search method for vector quantization is proposed in this paper. It makes
      use of the fact that in the generalized Lloyd algorithm (GLA) a vector in a
      training sequence is either placed in the same minimum distance partition (MDP)
      as in the previous iteration or in a partition within a very small subset of
      partitions. The proposed method searches for the MDP for a training vector only
      in this subset of partitions plus the single previous MDP. As the size of this
      subset is much smaller than the total number of codevectors, the search process
      is speeded up significantly. The creation of the subset is essential, as it has a
      direct effect on the improvement in computation time of the proposed method. The
      schemes that create the subset efficiently have been proposed. The proposed
      method generates a codebook identical to that generated using the GLA. It is
      simple and requires only minor modification of the GLA and a modest amount of
      additional memory. The experimental results show that the computation time of
      codebook training was improved by factors from 6.6 to 50.7 and from 5.8 to 70.4
      for two test data sets when codebooks of sizes from N = 16 to 2048 were trained.
      The proposed method was also combined with an earlier published method to further
      improve the computation time.

PMID- 16900696
TI  - A novel high-capacity data-embedding system.
AB  - In this paper, we present a novel data-embedding system with high embedding
      capacity. The embedding algorithm is based on the quantized projection embedding
      method with some enhancement to achieve high embedding rates. In particular, our
      system uses a random permutation of the columns of a Hadamard matrix as
      projection vectors and a fixed perceptual mask based on the JPEG default
      quantization table for the quantization step design. As a result, the data
      embedding system achieves 1/167 (1 bit out of 167 raw image bits) to 1/84 hiding
      ratios with a BER of around 0.1% in the presence of JPEG compression attacks,
      while maintaining visual distortion at a minimum.

PMID- 16900697
TI  - Halftone visual cryptography.
AB  - Visual cryptography encodes a secret binary image (SI) into n shares of random
      binary patterns. If the shares are xeroxed onto transparencies, the secret image
      can be visually decoded by superimposing a qualified subset of transparencies,
      but no secret information can be obtained from the superposition of a forbidden
      subset. The binary patterns of the n shares, however, have no visual meaning and
      hinder the objectives of visual cryptography. Extended visual cryptography [1]
      was proposed recently to construct meaningful binary images as shares using
      hypergraph colourings, but the visual quality is poor. In this paper, a novel
      technique named halftone visual cryptography is proposed to achieve visual
      cryptography via halftoning. Based on the blue-noise dithering principles, the
      proposed method utilizes the void and cluster algorithm [2] to encode a secret
      binary image into n halftone shares (images) carrying significant visual
      information. The simulation shows that the visual quality of the obtained
      halftone shares are observably better than that attained by any available visual
      cryptography method known to date.

PMID- 16900698
TI  - Personal recognition using hand shape and texture.
AB  - This paper proposes a new bimodal biometric system using feature-level fusion of
      hand shape and palm texture. The proposed combination is of significance since
      both the palmprint and hand-shape images are proposed to be extracted from the
      single hand image acquired from a digital camera. Several new hand-shape features
      that can be used to represent the hand shape and improve the performance are
      investigated. The new approach for palmprint recognition using discrete cosine
      transform coefficients, which can be directly obtained from the camera hardware,
      is demonstrated. None of the prior work on hand-shape or palmprint recognition
      has given any attention on the critical issue of feature selection. Our
      experimental results demonstrate that while majority of palmprint or hand-shape
      features are useful in predicting the subjects identity, only a small subset of
      these features are necessary in practice for building an accurate model for
      identification. The comparison and combination of proposed features is evaluated
      on the diverse classification schemes; naive Bayes (normal, estimated,
      multinomial), decision trees (C4.5, LMT), k-NN, SVM, and FFN. Although more work
      remains to be done, our results to date indicate that the combination of selected
      hand-shape and palmprint features constitutes a promising addition to the
      biometrics-based personal recognition systems.

PMID- 16900699
TI  - On the detection of simple points in higher dimensions using cubical homology.
AB  - Simple point detection is an important task for several problems in discrete
      geometry, such as topology preserving thinning in image processing to compute
      discrete skeletons. In this paper, the approach to simple point detection is
      based on techniques from cubical homology, a framework ideally suited for
      problems in image processing. A (d-dimensional) unitary cube (for a d-dimensional
      digital image) is associated with every discrete picture element, instead of a
      point in epsilon(d) (the d-dimensional Euclidean space) as has been done
      previously. A simple point in this setting then refers to the removal of a
      unitary cube without changing the topology of the cubical complex induced by the
      digital image. The main result is a characterization of a simple point p (i.e.,
      simple unitary cube) in terms of the homology groups of the (3d - 1) neighborhood
      of p for arbitrary, finite dimensions

PMID- 16900701
TI  - A single intrategmental amphetamine exposure induces transient behavioral
      sensitization in the rats.
AB  - Repeated treatment with psychostimulant drugs induces enduring behavioral
      sensitization and neuroadaptations which may play an important role in the
      development of drug addiction. However, different number and time course in drug
      administration and various lengths of drug withdrawal were employed in the
      literature, and there were inconsistent findings in the profile of extracellular
      dopamine level related to behavioral sensitization. Therefore, the effects of the
      number of drug exposure and the length of drug withdrawal period on the
      sensitized behavioral response were investigated in this study. Various lengths
      of amphetamine (AMPH) withdrawal (1, 3 and 5 days) after a single local
      administration of AMPH to bilateral ventral tegmental area (VTA) were used to
      observe the locomotor activity response. Besides, different amounts of
      administration of intra-VTA AMPH were given (1, 2 and 3 times of injection) to
      monitor the profile of travel distance and stereotypic movements of rats after 7
      days of drug withdrawal. An early and short-lived behavioral sensitization to the
      single intra-VTA AMPH administration was induced. In the repeated treatment
      group, more drug exposures were associated with escalating and robust levels of
      travel distance after 7 days of drug withdrawal. The authors speculated that the
      transient and, a later augmented locomotor activity response might represent
      respective phases in the development of behavioral sensitization, which in turn
      contributed to the formation of more lasting behavioral and neuroplastic changes
      associated with drug addiction.

PMID- 16900700
TI  - Changes in membrane cholesterol of pituitary tumor (GH3) cells regulate the
      activity of large-conductance Ca2+-activated K+ channels.
AB  - The effects of changes in membrane cholesterol on ion currents were investigated
      in pituitary GH3 cells. Depletion of membrane cholesterol by exposing cells to
      methyl-beta-cyclodextrin (MbetaCD), an oligosaccharide, resulted in an increase
      in the density of Ca2+-activated K+ current (IK(Ca)). However, no significant
      change in IK(Ca) density was demonstrated in GH3 cells treated with a mixture of
      MbetaCD and cholesterol. Cholesterol depletion with MbetaCD (1.5 mg/ml) slightly
      suppressed the density of voltage-dependent L-type Ca2+ current. In inside-out
      patches recorded from MbetaCD-treated cells, the activity of large-conductance
      Ca2+-activated K+ (BK(Ca)) channels was enhanced with no change in single-channel
      conductance. In MbetaCD-treated cells, voltage-sensitivity of BK(Ca) channels was
      increased; however, no change in Ca2+-sensitivity could be demonstrated. A
      negative correlation between adjacent closed and open times in BK(Ca) channels
      was observed in MbetaCD-treated cells. In inside-out patches from MbetaCD-treated
      cells, dexamethasone (30 microM) applied to the intracellular surface did not
      increase BK(Ca)-channel activity, although caffeic acid phenethyl ester and
      cilostazol still opened its probability effectively. However, no modification in
      the activity of ATP-sensitive K+ channels could be seen in MbetaCD-treated cells.
      Current-clamp recordings demonstrated that the cholesterol depletion maneuver
      with MbetaCD reduced the firing of action potentials. Therefore, the increase in
      BK(Ca)-channel activity induced by membrane depletion may influence the
      functional activities of neurons or neuroendocrine cells if similar results occur
      in vivo.

PMID- 16900702
TI  - Contrast of directional influence upon motor overflow between submaximal and
      maximal static exertions.
AB  - This study investigated exertion-dependent motor overflow among healthy adults
      when they performed isometric tasks with contralateral joints in different task
      directions. Twenty healthy adults (10 males and 10 females, mean age = 26.2 yrs)
      were instructed to complete a set of isometric contractions of various force
      vectors with the shoulder, elbow, and wrist joints, in a total of ten motor tasks
      at submaximal and maximal intensities (50%, 100% maximal voluntary contractions).
      The electromyographical activities from eight muscles of the unexercised upper
      limb were recorded to characterize intensity of motor overflow during sustained
      isometric contraction. Both occurrence frequency and magnitude of motor overflow
      in terms of standardized net excitation (SNE) increased with exertion level for
      all joint movements (P < 0.001). Additionally, the motor overflow magnitude
      depended strongly on the task direction of maximal isometric contraction (P <
      0.05). Motor overflow was particularly augmented by the contralateral isometric
      contractions where task directions were opposed to gravity. However, such a
      directional effect upon SNE was not evident during submaximal contraction (P >
      0.05). The difference of the net excitation between maximal and submaximal
      contraction (DNE(100%-50%MVC) data) indicated that the pectoralis major and
      triceps brachii consistently exhibited a marked recruitment in reaction to change
      in task direction of isometric contraction. Patterned motor overflow may be
      physiologically relevant to topological mapping of the ipsilateral pathways and
      altered effectiveness of use-dependent interhemispherical connectivity. The
      current observations provide better insight into gain in muscle strength due to
      contralateral exercise.

PMID- 16900703
TI  - Comparative proteomics of apoptosis initiation induced by 5-fluorouracil in human
      gastric cancer.
AB  - 5-Fluorouracil is the first choice chemotherapeutic drug for patients with
      gastric cancer, but the mechanism that 5-fluorouracil plays the anti-tumor role
      remains unclear. The aim of this study was to clarify correlated [corrected]
      proteins induced by 5-fluorouracil in the apoptosis-initiation of human gastric
      cancer (MGC-803) cells. The time point of apoptosis-initiation induced by 5
      fluorouracil in MGC-803 cells was determinated using 5-fluorouracil-withdrawal.
      Two-dimensional electrophoreses (2-DE) were employed to compare the differentials
      of protein expressions of the MGC-803 cells at the apoptosis-initiation phase and
      those of the MGC-803 cells untreated with 5-fluorouracil. The differential
      proteins included 14 upregulated proteins and 8 downregulated proteins. They
      indicated a more-than-doubled alteration. These proteins were digested in gels by
      trypsin and the mass of generated peptides were measured by matrix assisted laser
      desorption ionization time of flight mass spectrometry (MALDI-TOF-MS). The data
      obtained from peptide mass fingerprinting (PMF) were searched out using the
      internet available database mascot (http://www.matrixscience.com). The results
      showed that proteomics analyses have evidenced that many kinds of proteins are
      involved in the apoptosis initiation of human gastric cancer MGC-803 cells. These
      proteins are related to metabolism, oxidation, cytoskeleton and signal
      transduction and other aspects of cells. In conclusion, the experiment model of
      apoptosis-initiation of human gastric cancer MGC-803 cells induced by 5
      fluorouracil based on proteomic analysis has been established, giving an impetus
      to researches of the mechanism of apoptosis in human gastric cancer, and laying a
      foundation for the selection of potential drug precursors specific for inducing
      apoptosis-initiation in human gastric cancer.

PMID- 16900704
TI  - Dendritic spines of developing rat cortical neurons in culture.
AB  - The formation of spines and their association with synapses were examined in
      developing cultured rat cortical neurons using fluorescence labeling techniques.
      Small protrusions were found on the processes of cultured cortical neurons after
      seven days in vitro (DIV), and the density of protrusions almost halved during
      the second week in vitro, after which it remained unchanged throughout the third
      week in vitro. The proportion of protrusions associated with the accumulation of
      the presynaptic marker, synaptophysin, increased steadily from <5% at 7 DIV to
      approximately 50% at 21 DIV. Based on the absence or presence of an enlargement
      at the end, protrusions on processes were further divided into filopodia and
      spines, respectively. The percentage of protrusions that were classified as
      spines increased steadily from approximately 5% at 3-4 DIV to approximately 80%
      at 18-20 DIV. The percentage of spines associated with synaptophysin accumulation
      increased gradually as the cortical neurons developed in vitro, reaching a
      plateau of approximately 40% after two weeks. However, the percentage of
      filopodia associated with synaptophysin accumulation never exceeded 5% during the
      first three weeks in vitro. Double-label staining the microfilaments and beta
      tubulin or phosphorylated neurofilament H of cultured neurons further revealed
      many spines without any nearby axon-like processes. These findings suggest that
      spines are the dominant form of protrusion on the processes of more mature
      cortical neurons, that spines are the preferential sites where synapses reside,
      and that maintaining constant contact with axons is not essential for the
      formation of spines in cultured cortical neurons.

PMID- 16900705
TI  - Duration selectivity of bat inferior collicular neurons improves with increasing
      pulse repetition rate.
AB  - Insectivorous big brown bats, Eptesicus fuscus, progressively increase the pulse
      repetition rate (PRR) throughout the course of hunting. While increasing PRR
      conceivably facilitates bats to extract information about the targets, it also
      inevitably affects sensitivity of their auditory neurons to pulse parameters. The
      present study examined the effect of increasing PRR on duration selectivity of
      this bat's inferior collicular (IC) neurons by comparing their impulse-duration
      functions determined at different PRRs. Impulse-duration functions plotted with
      the number of impulses in response to single pulses against pulse duration at
      different PRRs were described as short-pass, band-pass, long-pass, and all-pass.
      Short- or long-pass neurons discharged maximally to a range of short or long
      pulse durations. Band-pass neurons discharged maximally to one pulse duration.
      These three types of IC neurons were called duration tuned neurons. All-pass
      neurons were not duration tuned because they did not discharge maximally to any
      pulse duration. Increasing PRR improved duration selectivity of IC neurons by (1)
      increasing the number of duration tuned neurons; (2) decreasing the critical
      duration concomitant with increasing slope of the impulse-duration function; and
      (3) decreasing the 50% duration range of the impulse-duration function. This
      improved duration selectivity with PRR may potentially facilitate prey capture by
      bats.

PMID- 16900706
TI  - A severe vicious cycle in uncontrolled subarachnoid hemorrhage: the effects on
      cerebral blood flow and hemodynamic responses upon intracranial hypertension.
AB  - In subarachnoid hemorrhage (SAH), Cushing postulated that the increase in
      systemic arterial pressure (SAP) in response to elevation of intracranial
      pressure (ICP) was beneficial to cerebral perfusion. However, in uncontrolled
      SAH, the increased SAP may cause more bleeding into the subarachnoid space and
      further increase the ICP. We created an animal model to simulate SAH by
      connecting a femoral arterial catheter to the subarachnoid space. The global
      cerebral blood flow (CBF) was measured with a venous outflow method. The purposes
      were to observe the CBF change under the simulated SAH, and to evaluate the
      effects of an adrenergic blocker and a vasodilator. In addition, spectral
      analysis of the aortic pressure and flow was employed for the analysis of
      hemodynamic changes at various ICP levels. When the femoral arterial blood was
      allowed to flow into the subarachnoid space, the ICP was elevated. The Cushing
      response to increased ICP caused an increase in SAP. A vicious cycle was
      generated between ICP and SAP. The CBF under the vicious cycle was greatly
      depressed. The dog developed pulmonary edema (PE) within 5 mins. An alpha
      adrenergic blocker (phentolamine) and a vasodilator (nitroprusside) were
      beneficial to the reduction of SAP and ICP, improvement of CBF, and prevention of
      PE. Hemodynamic analysis revealed that graded increases in ICP caused increases
      in SAP, total peripheral resistance, arterial impedance, and pulse reflection
      with decreases in stroke volume, cardiac output and arterial compliance. The
      hemodynamic changes may contribute to acute left ventricular failure that leads
      to pressure and volume loading in the lung circulation, and finally acute PE.

PMID- 16900707
TI  - Changing role of medical college teachers.

PMID- 16900708
TI  - Trend of blood groups and Rh factor in the twin cities of Rawalpindi and
      Islamabad.
AB  - OBJECTIVE: To determine the prevalence of different blood groups and Rh factors
      in a random population sample from urban and rural areas of Rawalpindi and
      Islamabad region of Pakistan. METHODS: Blood group and Rh factor determination
      was carried out by the antigen-antibody agglutination test from October 2003 to
      October 2004, and encompassed 2518 subjects. RESULTS: The percentages of various
      groups among male and female subjects, respectively, were recorded as 27.01% and
      24.02% (for blood group A), 33.75% and 32.87% (for blood group B), 8.93% and
      11.20% (for blood group AB) and 30.31% and 31.91% (for blood group O). The Rh
      positive and negative distribution in the studied population was 92.45% and 7.55%
      respectively. CONCLUSION: The determination of the frequency of blood groups in
      the region would not only help in blood transfusion services, but also eliminate
      the risk of erythroblastosis foetalis in the neonates.

PMID- 16900710
TI  - Epidemiology of genital tuberculosis in infertile population.
AB  - OBJECTIVE: To assess the frequency of genital tuberculosis in infertile women,
      its clinical presentation and association with socio-economic status and
      geographical latitude and to compare various modes of diagnosis and efficacy of
      therapy. METHODS: This cross-sectional study was carried out in the Gynaecology
      and Obstetric Department (Unit Ill), Federal Government Services Hospital,
      Islamabad for a period of two years, from January 1, 2001 to December 31, 2003. A
      protocol for fertility work-up included complete history, examination, monitoring
      of ovulation and assessment of male factor. During laparoscopy peritoneal fluid
      was obtained for cytology and Ziehl-Neelsen (ZN) staining in suspicious cases of
      chronic inflammation was carried out. Endometrial curettings were obtained for
      histopathology and culture in Lowenstein-Jensen (LJ) medium. After confirmation
      of diagnosis, anti-tuberculosis therapy (ATT) was started. Surgical management
      was done in advanced stage disease with tubo-ovarian masses. RESULTS: Out of 7628
      patients who attended the gynae out-patient department, 534 (7%) women were
      infertile, of which 2.43% had genital tuberculosis. Six patients had early stage
      disease (46.15%) and were completely cured, but three patients had successful
      pregnancy outcome (23%). Seven had advanced stage disease (53.85%) and required
      conservative surgery in addition to ATT. Among these patients, although
      tuberculosis was cured, yet fertility could not be achieved. All patients
      belonged to low socio-economic class, and 85% belonged to Northern areas of the
      country, who were poor and deprived of health facilities. CONCLUSION: It is
      essential for a gynaecologist working in developing countries to anticipate
      possibility of genital tuberculosis in infertile patients.

PMID- 16900709
TI  - The efficacy of conventional PCNL and two modifications to standard procedure.
AB  - OBJECTIVE: To compare the efficacy of conventional Percutaneous Nephrolithotomy
      (PCNL) with two of its modified procedures. METHODS: A randomized controlled
      trial, was performed on 60 patients undergoing PCNL. Cases of renal stone
      regardless of stone size and configuration, having pre-operative negative urine
      culture, no coagulopathy, and no visible residual stone in intra-operative
      fluoroscopy, were included. They were randomly divided into 3 groups of 20 cases
      each with nephrostomy tube (NT) and temporary ureteral catheter (TU) in group A,
      only TU in group B and only indwelling ureteral catheter (IU) in group C. Mean
      age of cases were 43.2 (25-70), 40.1 (25-73), and 44 (25-70) years in groups A ,
      B and C, respectively (P = 0.6). Procedures were performed under general
      anaesthesia, using standard techniques for access and lithotomy. Forty-eight
      hours, 2 weeks and 3 months after PCNL, plain X-ray abdomen, ultrasonography and
      IVP were performed for each case. RESULTS: Only one case in group A had urinary
      leakage after removal of nephrostomy tube. No cases in the other two groups
      encountered this problem. There was no haemorrhagic episode. Ultrasonic
      evaluation showed mild residue in 3, 1 and 1 cases of groups A, B and C,
      respectively (P = 0.2). No collective fluid was found in these groups. IVP showed
      dilatation without obstruction in 3 subjects of group A and none in group B or C
      (P = 0.03). CONCLUSION: Tubeless PCNL seems to be accompanied by better outcome.
      So, further evaluation on more patients seems necessary.

PMID- 16900711
TI  - Transfer of extensor carpi radialis brevis as an extensor to extensor motor
      transfer (EEMT) in ulnar nerve palsy.
AB  - OBJECTIVE: To evaluate functional outcome and correction of deformity with
      extensor carpiradialis brevis motor transfer to replace the intrinsic muscles as
      an extensor to extensor motor transfer (EEMT). METHOD: This was a prospective
      observational study with one group pretest posttest design conducted from 1996 to
      2004. Convenience sampling technique was used and the sample size was twenty one.
      The independent variable was transfer of extensor carpiradialis brevis to replace
      the intrinsic muscles. The dependent variable was functional outcome and the
      correction of deformity. The extraneous variables were age, sex interval between
      injury and transfer as well as local factors related to wound and grafts used.
      The average follow up was 22.5 months. RESULTS: The mean preoperative unassisted
      extensor lag was 56.79 +/- 10.39 which improved to 9.6% +/- 5.4 (correction of
      83%) at six months after surgery. With open hand assessment 76.19% reported good
      to excellent results, while 79.89% achieved good to excellent results with closed
      hand assessment. The mechanism of closing was good to excellent in 89.42% cases,
      however only 71.42% patients considered their hands good to excellent.
      Significant problems were seen with use of tendoachilles as a graft. CONCLUSION:
      Extensor carpiradialis brevis transfer to replace the intrinsic muscles as an
      extensor to extensor motor transfer can achieve good functional outcome as well
      as correction of deformity despite shortcomings in physical rehabilitation.

PMID- 16900712
TI  - Knowledge and skills in community oriented medical education (COME) self-ratings
      of medical undergraduates in Karachi.
AB  - OBJECTIVE: To assess the satisfaction of medical students regarding community
      oriented knowledge and skills that are proposed to be part of the current
      undergraduate medical curriculum. METHODS: Competencies listed in the regulations
      for medical education designed by the Pakistan Medical and Dental Council (PMDC)
      were used to develop a self-administered questionnaire. Using the questionnaire
      220 final year students of 3 public sector medical schools self-rated the
      knowledge and skills that should be part of the curriculum. For analysis the
      questions were grouped into courses of Basic, Clinical and Community Health
      Sciences. Students ranked their perceptions on a Likert scale of 0-4 for each
      question. Descriptive analysis was done to calculate the proportion of satisfied
      and dissatisfied students using the median of the highest possible score as the
      cut off. RESULTS: The analysis of knowledge gained found a greater proportion of
      satisfied students with the Basic (55.9%) and Clinical Sciences (50.9%) courses
      than the Community Health Sciences course (45.5%). Analysis of skills acquired
      uniformly showed a low percentage of satisfied students for Basic (39.1%),
      Clinical (29.7%) and Community Health Sciences (19.1%). The proportion of
      students dissatisfied with their knowledge and skills for different courses
      ranged from 38.2-85%. CONCLUSION: Students perceive that current medical school
      curricula are unable to meet the required standards. Proper implementation of
      community oriented curricula is the first step towards effective health care
      provision.

PMID- 16900713
TI  - Association of serum C-reactive protein and LDL:HDL with myocardial infarction.
AB  - OBJECTIVE: To identify frequency of the following markers of atherosclerosis
      risk: high C-Reactive Protein (CRP) and ratio between serum levels of low density
      lipoprotein (LDL) and high density lipoprotein (HDL) and to determine the
      association of high serum CRP levels and LDL:HDL in the patients presenting at
      NICVD with first myocardial infarction. METHODS: This case control study was
      conducted at National Institute for Cardiovascular Disease (NICVD), in Karachi,
      comprising of 50 male patients of acute myocardial infarction (without any other
      co-morbidity) and 50 matching controls. RESULTS: In this study, CRP levels were
      significantly high (p = 0.003) and serum HDL levels significantly low (p = 0.006)
      in patients as compared to controls. Serum LDL levels and the ratio of LDL and
      HDL were not significantly different among the two groups. CONCLUSION: High serum
      CRP levels rather than high LDL:HDL are associated with myocardial infarction in
      the patients presenting at NICVD with first myocardial infarction.

PMID- 16900714
TI  - Serum thiocyanate levels in smokers, passive smokers and never smokers.
AB  - OBJECTIVE: To compare the serum thiocyanate levels in smokers, passive smokers
      and never smokers. METHODS: Serum thiocyanate was analyzed on 135 self reported
      smokers, never smokers and passive smokers by UV-Spectrophotometry (Manual method
      of Bowler). RESULTS: The mean serum thiocyanate concentration (112 +/- 36.6
      micromol/L) of smokers was significantly higher (p value < 0.001) as compared to
      passive (55 +/- 16.1 micromol/L) and never smokers (41 +/- 6.6 micromol/L). The
      serum thiocyanate of female smokers (133 + 28.7 micromol/L) was higher (p value <
      0.05) than male smokers (103 +/- 36.3 miccromol/L). Serum thiocyanate showed 91%
      sensitivity, 80% specificity and 84% accuracy at > or = 60 micromol/L for
      smokers. CONCLUSION: Serum thiocyanate is significantly higher in smokers than
      passive and never smokers. Serum thiocyanate at > or = 60 micromol/L may be
      considered as cutoff value for distinguishing smokers from non-smokers for future
      studies.

PMID- 16900715
TI  - E-psychiatry: uses and limitations.
AB  - The importance of using e-mail as a mode of communication between physicians and
      patients is becoming more common and popular because of its speed and
      effectiveness. Though little research has been done on the use and impact of e
      mail in psychiatry but evidence is available about its frequent use both by the
      patients and the psychiatrists. This review paper attempts to examine the
      importance of this mode of communication, with its risks and threats. The
      inherent limitations of the message transfer method and the magnitude of its
      usage with benefits and hazards, both for the doctors and patients, will also be
      analyzed. The recommended guidelines concerning its usage are also present. It is
      concluded that though e-mail communication is fast gaining popularity, its impact
      on psychiatry is yet to be seen keeping in view the importance of direct
      communication with patients in the practice of psychiatry. It appears that with
      the development of future technologies, e-psychiatry will become relatively risk
      free and a source of help for the general health care system.

PMID- 16900716
TI  - One year experience of MRI under general anaesthesia.
AB  - A case series over one year of our experience of using Propofol and Laryngeal
      mask airway (LMA) in children under 10 years of age undergoing MRI under general
      anaesthesia is presented. All paediatric patients under the age of ten attending
      out-patient department were included in the case series starting from January
      1st, 2004 till December 31st, 2004. All patients underwent general anaesthesia
      using Propofol / LMA technique as described in detail in communication below. A
      total of 78 children were included; the only patient requiring intubation was the
      youngest: a neonate of 1 day who had a large orbital mass. Propofol in the dose
      of 2 mg/kg and an appropriate size LMA according to weight of the patient was
      used. Majority of the patients (67) had a brain or head MRI for 'developmental
      delay', 5 patients had a brain MRI for a 'mass lesion' and 5 patients had a lumbo
      sacral MRI for 'abnormal growth'. There was only one complication when a child
      with history of seizures, seized on recovery and had to be subsequently admitted
      to the Emergency Room for observation. No other morbidity or mortality was noted.
      All patients were outpatients. We can conclude based on our results that
      providing GA for paediatric patients undergoing MRI with Propofol and LMA can be
      safe and effective in outpatient radiology.

PMID- 16900717
TI  - Scope of laparoscopic anti reflux surgery in Pakistan.

PMID- 16900718
TI  - Tuberculosis of the scapula.
AB  - Tuberculosis (TB) of the scapula is an extremely rare presentation of
      osteoarticular tuberculosis. In a tuberculosis endemic setting with a rising
      burden of acquired immunodeficiency syndrome, this rare presentation may become
      more frequent. The common presentation is with longstanding Complaints of pain
      and swelling in the shoulder region, typically in young adults. Classic
      radiographic features include a well defined radiolucent lesion with minimal
      sequesteration. The erythrocyte sedimentation rate is usually elevated and
      initially these patients are frequently mis-diagnosed and thus a high index of
      clinical suspicion is required. Medical therapy with antituberculous drugs is the
      standard modality of treatment. This case serves to higlight the salient features
      of scapular TB.

PMID- 16900719
TI  - Systemic mastocytosis: a rare entity.
AB  - An 18 year old female presented with generalized maculopapular rash and
      headaches. The skin and bone marrow biopsy revealed numerous mast cells which
      stained metachromatically with giemsa and toludine blue stains and showed
      positivity with CD68 and CD117 on immunohistochemistry. Her clinical presentation
      and laboratory findings were consistent with the diagnosis of indolent systemic
      mastocytosis. Because of the benign course of the disease, patient was offered
      only anti-histamine drugs that were quite successful in alleviating her symptoms.

PMID- 16900720
TI  - Mixed epithelial and stromal tumour of kidney.
AB  - Mixed epithelial and stromal tumour of kidney is a recently described, rare
      entity and includes cases previously termed as cystic hamartoma of renal pelvis
      and adult mesoblastic nephroma. We report a case of 36 years old female who
      presented with a history of recurrent loose stools for 5 years. During ultrasound
      abdomen, a solid right renal mass was incidentally found in upper pole of right
      kidney. On gross examination it was a 3.5 cm diameter mass which was
      microscopically composed of both epithelial and stromal components in the form of
      cystically dilated tubules and fascicles of spindle shaped cells. These cells
      stained positive for alpha smooth muscle actin, desmin, progesterone receptors
      and negative for estrogen receptors.

PMID- 16900721
TI  - Water-pipe smoking: a threat never realized.

PMID- 16900722
TI  - [Will clinical competence be replaced through modern technology?].

PMID- 16900723
TI  - [Bio-psycho-social history--is it still up to date in the time of media
      communication?].
AB  - Specialization in medicine changes the kind of communication between doctor and
      patient. The direct personal communication is quite often complemented by the
      indirect communication via interactive media. A clinical investigation still
      demands a broad bio-psycho-social anamnesis which should encompass the history of
      the illness, the patient, and his/her ailment. The bio-psycho-social anamnesis is
      subdivided into nine steps: Joining, "map", actual disease, former illnesses,
      family history, personal development, social anamnesis, overview of the
      functioning of the systems, finalization of the anamnesis. The different steps
      are explained, and adequate techniques of exploration are described. How to
      conduct a professional doctor-patient conversation and exploration can similarly
      be learnt as the techniques of a physical investigation. These communication
      skills should be continuously taught during the education of medical students as
      well as during the further training of physicians.

PMID- 16900724
TI  - [The clinical examination in cardiology].
AB  - The main manifestations of cardiac diseases are dyspnea, chest pain,
      palpitations, giddiness and syncope. A careful evaluation of subjective symptoms
      during history taking allows a rapid identification of an ischaemic heart
      disease, heart failure or cardiac arrhythmias. The additional clinical findings
      during bedside examination by inspection of the jugular veins, palpation of
      cardiac impulses and auscultation of heart sounds and murmurs are often
      sufficient to diagnose most of the frequent underlying disorders, such as
      valvular diseases, heart failure or pulmonary hypertension. The clinical
      assessment remains essential to select the most appropriate additional tests,
      such as echocardiography, scintigraphy, computer tomography or coronarography.
      Systematic teaching of the clinical skills should remain a central element in the
      formation of medical students and clinical fellows.

PMID- 16900725
TI  - [Heart murmur--auscultation or echocardiography in the diagnostic assessment of
      congenital or valvular heart disease?].
AB  - The incidence of patients with degenerative valvular but also of patients with
      congenital heart disease surviving until adulthood or even old age will increase
      in the next decades. Auscultation with the stethoscope remains an important
      diagnostic means in the detection and treatment of heart disease. Heart murmurs
      (especially systolic heart murmurs) are extremely common. There are helpful clues
      to differentiate heart murmurs. It can occasionally be relatively simple to
      differentiate a systolic murmur due to valvular heart disease from an innocent,
      ejection murmur; however, there are important limitations of auscultation.
      Overall, auscultation and clinical examination alone do not suffice to correctly
      diagnose and treat patients with heart failure or a murmur Clinically significant
      aortic stenosis, aortic regurgitation and mitral regurgitation as well as
      hypertrophic cardiomyopathy are not uncommonly missed or misinterpreted. An
      echocardiographic exam is mandatory in all patients with more than a soft
      systolic murmur, any diastolic murmur, cardiac symptoms and/or ECG changes.

PMID- 16900726
TI  - [Physical examination of the lung--value and limits].
AB  - Sensitivity and specificity of clinical findings for the diagnosis of pulmonary
      diseases is often poor, or information on test characteristics of particular
      findings is even missing. Nevertheless, a meticulous clinical exam remains a
      cornerstone in clinical practice. Quite often clear-cut findings may provide
      valuable diagnostic information. Furthermore, history taking and painstaking
      physical examination foster the confidence between patients and physicians, which
      is urgently needed in a time of machine-dominated medical practice.

PMID- 16900727
TI  - [Does the ultrasound make the clinical examination of the abdomen unnecessary?].
AB  - The clinical examination holds an important significance in today's medical way
      of life. Especially in Gastroenterology, the conversation including a meticulous
      anamnesis, the observation of a patient and the physical examination are the key
      to diagnosing a multitude of diseases. And are also indispensable for a sensible
      and purposeful use of all of today's available technical resources.

PMID- 16900728
TI  - [The clinical examination of the critically ill patient in the intensive care
      unit].
AB  - Various circumstances hinder the clinical examination of a patient in an
      intensive care unit (ICU). Nevertheless, the clinical assessment is crucial for
      the formulation of a diagnostic and therapeutic plan. History and clinical
      examination need to be performed timely and efficiently. They are best done in a
      structured manner, so that no important details are missed. The doctor should
      follow the concept of "A B C", in which "A" stands for airways, "B" for breathing
      and "C" for circulation. It is essential that some pathological findings in the
      clinical examination prompt immediate therapeutic interventions to avoid further
      deterioration. Thorough clinical assessment is normally performed at the time of
      patient's admission to the ICU. However, parts of history and clinical
      examinations may still be missed. It is therefore crucial that this information
      is obtained as soon as possible as it may help with the management of the
      patient. Clinical examination is repeated at the daily ward rounds as well as at
      any time that the patient's condition changes. Results of tests and data
      collected from monitoring equipment should be viewed as an addition to the
      patient's clinical assessment and must not distract the clinician from the
      patient's clinical condition. Precise documentation of the findings is vital to
      allow comparison of the patient's progress on a daily basis and to provide
      continuity of care.

PMID- 16900729
TI  - [History and clinical examination in rheumatology--key to diagnosis and
      prognosis].
AB  - History and clinical examination are key to diagnosis and prognosis in
      rheumatology. In the area of soft tissue rheumatism, there is no other diagnostic
      possibility which could replace clinical examination. Clinical examination also
      plays a very important role in the diagnosis of the other rheumatic disorders.
      With a competent clinical examination one can often eliminate the need for
      additional costly and/or time consuming investigations. In addition, diagnosing
      by purely careful and competent clinical examination is a highly gratifying
      activity for the medical doctor. The competent examiner should also be able to
      derive prognostic conclusions directly from the clinical examination. This is
      especially important for the more frequent disorders such as soft tissue
      rheumatism or back problems, where diagnostic imaging is only helpful if
      interpreted in the context of the pertinent clinical question.

PMID- 16900730
TI  - [The neurological examination--a lasting art].
AB  - The neurological examination is a challenge for both the physician as well as the
      patient. Its goal is the formation of a syndrome--but not the diagnosis--with the
      tools of the case history and the neurological examination, which are presented
      coarsely, weighted, ostentatious, and provocative at times.

PMID- 16900731
TI  - [The in vivo pediculicidal efficac of Prioderm Cream Shampoo formulation].
AB  - BACKGROUND: Head louse infestations are prevalent worldwide. Over the past 20-25
      years, 15-20% of all children in Israel between 4 and 13 years of age have been
      infested with head lice. This is mainly due to the existence of ineffective
      pediculicides on the market. OBJECTIVE: To examine the pediculicidal efficacy and
      safety of Prioderm Cream Shampoo in an open clinical study. METHODS: The active
      ingredient of Prioderm Cream Shampoo is malathion (1%) and it was applied to the
      hair of infested children three times for 10 minutes at 5-day intervals. RESULTS:
      Of 419 children examined, aged 6-14 years, from four schools in Jerusalem, 109
      (26.0%) were infested with lice and eggs, while 110 (26.3%) were infested only
      with nits. All 109 louse-infested children were included in the study while 86
      (78.8%) complied with the instructions for use. Treatment was successful in 79
      children (91.8%), while failure was observed in 3 children after the first
      treatment and in 4 children after the third treatment. Although 21.5% of the
      children disliked the odor of the product, there were no significant side effects
      related to this formulation. CONCLUSIONS: The product was very effective in
      controlling louse infestations under clinical conditions and caused no serious
      side effects.

PMID- 16900732
TI  - [Acute generalized exanthematous pustulosis (AGEP) following intake of
      furosemide].
AB  - INTRODUCTION: Acute generalized exanthematous pustulosis (AGEP) is an acute
      pustular eruption with unique clinical features, a rapid clinical course and a
      typical histopathology. The causative agents are mostly drugs but other triggers
      have also been described. CASE REPORT: A 52 year-old woman with a history of
      diabetes mellitus type II, dyslipidemia and osteomyelitis was treated for about a
      year with metformin (Glucophage) and simvastatin (Simovil) tablets. Due to the
      osteomyelitis, the patient was started on a regimen of intravenous vancomycin as
      well as furosemide tablets (Fusid) for pedal edema. About seventeen days after
      beginning treatment with vancomycin and a week after starting furosemide the
      patient was hospitalized due to an acute pruritic pustular eruption, involving
      most of her body surface area. Both vancomycin and furosemide treatment were
      discontinued, and topical treatment was provided. The clinical course was rapid
      with spontaneous resolution of the pustules followed by a characteristic pin
      point post-pustular desquamation. The morphological, clinical and histological
      findings suggested a definite case of AGEP based on the EuroSCAR scoring system.
      The latent period between the initiation of medication intake and the appearance
      of AGEP, as well as a literature search, suggest that furosemide might be the
      incriminated drug. CONCLUSION: We have described a rare case of typical AGEP most
      probably induced by furosemide.

PMID- 16900733
TI  - [Subacute cutaneous lupus erythematosus induced by terbinafine].
AB  - BACKGROUND: The onset of subacute cutaneous lupus erythematosus (SCLE) may be
      associated with the administration of a variety of drugs. Terbinafine, an oral
      antifungal agent, which rarely causes cutaneous eruptions, has been implicated as
      the cause or exacerbation of cutaneous lupus erythematosus in several patients.
      CASE: A 59-year-old man had received oral terbinafine for onychomycosis. The
      patient had a history of SCLE, which was in complete remission during the last 5
      years. A month after initiating treatment with terbinafine the patient developed
      SCLE, which was diagnosed clinically and by histology. He had typical
      papulosquamous lesions. Immunological studies showed elevated titers of anti
      nuclear antibodies. Following discontinuation of terbinafine therapy and under
      the treatment of systemic and topical steroids, a slow resolution of the eruption
      was noted over several weeks. CONCLUSIONS: This report, along with previous cases
      described, suggests the association between terbinafine therapy and the onset or
      exacerbation of SCLE often occurring in a patient with history of systemic lupus
      erythematosus or SCLE.

PMID- 16900734
TI  - [Long-term effects of PUVA therapy on Israeli patients with vitiligo].
AB  - BACKGROUND: Long-term treatment of psoriasis patients with PUVA (psoralen and
      ultraviolet A) is associated with an increased risk of photoaging and non
      melanomic skin cancer, and perhaps of melanoma as well. Very little information
      is available on the long-term effects of PUVA treatment on vitiligo patients in
      general, and specifically on the risk of developing skin tumors. Among vitiligo
      patients treated with PUVA or heliotherapy, only a few cases of squamous cell
      carcinoma (SCC) have been described. OBJECTIVE: The objective of this research is
      to examine the long-term effects of PUVA treatment among vitiligo patients and
      the incidence of long-term side effects, including various types of skin cancers.
      PATIENTS AND METHODS: The medical files of all patients treated with PUVA at the
      Rabin Medical Center and the Emek Medical Center between 1982 and 1996 were
      surveyed. Each patient was interviewed by telephone and then invited to come in
      for a medical examination. RESULTS: A total of 28 out of 31 patients completed
      the questionnaire, and 12 of them were also examined. The average age of the
      patients was 47 years (range 25-84). The average amount of radiation to which
      each patient was exposed was 546.8 J/cm2 (range 26.5-1561), with a median of
      336.8 J/cm2. The average number of treatments per patient was 84.2 (median 77).
      The average time that elapsed since beginning the treatment was 11 years (range 7
      20), and the average time since treatment ended was 9.4 years (range 2-23).
      Partial or total repigmentation was experienced by 60% of the patients. In 18% of
      the patients, total or almost total repigmentation was seen, which lasted an
      average of 46 months. No skin cancer of any kind was seen in any of the patients.
      CONCLUSION: A recurrence of the illness was seen in all the vitiligo patients who
      had responded to PUVA treatment. Long-term treatment with PUVA for vitiligo
      patients does not entail photoaging damages or increased risk of skin cancer.

PMID- 16900735
TI  - [Allergic contact dermatitis to cocamidopropyl betaine among Israeli patients
      with cosmetic allergy].
AB  - INTRODUCTION: Cocamidopropyl betaine (CAPB) is an amphoteric surfactant commonly
      used in rinse-off cosmetic products. There is still a debate concerning the
      actual allergen in CAPB. OBJECTIVE: To evaluate the prevalence of CAPB allergy
      and its characteristics among Israeli patients. METHODS: A hundred consecutive
      patients with suspected cosmetic allergy were patch tested. They underwent
      standard and cosmetic series patch tests. RESULTS: Six patients, all females,
      were allergic to CAPB. Relevance rate was 66%. No significant characteristics
      were found among allergic patients. CONCLUSION: The rate of CAPB allergy is
      similar to the prevalence worldwide. CAPB became one of the leading causes of
      cosmetic allergy.

PMID- 16900736
TI  - [Thalidomide therapy for discoid lupus erythematosus].
AB  - INTRODUCTION: Discoid lupus erythematosus (DLE) is a chronic form of cutaneous
      lupus. Thalidomide has been reported as an effective treatment in at least 200
      cases of severe DLE. In this article we studied the efficacy and adverse effects
      of thalidomide in 10 patients with disseminated DLE. METHODS: This report
      presents the retrospective evaluation of 10 patients treated with thalidomide in
      our department during the period 1996-2005. RESULTS: All patients treated with
      thalidomide had been unresponsive to at least two other systemic treatments. The
      patients were treated with low-dose thalidomide of 50-200 mg per day. The dose
      was tapered after a clinical remission. All patients had a favorable response
      within 6 weeks. Of 10 patients 9 had complete regression of lesions. Four
      patients remain free of disease without maintenance treatment and 5 patients
      relapsed after cessation of thalidomide. All relapses responded after the
      reinstitution of the drug. The side effects of thalidomide treatment were mostly
      transient. The most common adverse effects were sedation and weight gain. Two
      patients developed peripheral sensory neuropathy resolved with discontinuation of
      thalidomide. Two patients of premenopausal age reported amenorrhea. CONCLUSION:
      Low-dose thalidomide treatment is an effective treatment option for discoid lupus
      erythematosus in cases resistant to other treatments. It is essential to be
      conversant with all the precautions in order to minimize the risks of side
      effects.

PMID- 16900737
TI  - [Pemphigus vulgaris--an alternative for steroid treatment?].
AB  - Pemphigus vulgaris is an autoimmune disease with a well-established immunological
      basis. Treatment is based on high dose and maintenance systemic corticosteroids.
      We report on a patient with a recurrence of full-blown pemphigus vulgaris after a
      trial of alternative hypnosis therapy to replace the corticosteroids.

PMID- 16900738
TI  - [Burnout among Israeli Transplantation Coordinators].
AB  - BACKGROUND: The role of the Transplant Coordinator (TC) is extremely demanding,
      as the TC faces a bereaved family at its most difficult moment, with a request
      for the body parts of a newly-lost family member. It is easy to assume that the
      burnout rate among TC is very high. AIM: This study examined the incidence of
      burnout among TC's in Israel, and factors influencing this burnout. METHODS: All
      26 TC's in Israel responded to a questionnaire in which they rated 12 statements
      concerning emotionality, control, responsibility and satisfaction. Their
      responses and the ratio between burnout and the factors in question were analyzed
      statistically. RESULTS: The three factors that influenced the burnout were
      control, the sense of satisfaction and self-realization, and the sense of
      responsibility. In an ascending scale from 1-5 it was found that TC's sense a
      high level of control (4.19 +/- 0.56), satisfaction (4.05 +/- 0.75) and
      responsibility (3.65 +/- 0.72). The mean level of a sense of burnout was
      relatively low (-2.25 +/- 0.50). A significantly negative correlation was found
      between the feeling of control and the burnout level, as the sense of control was
      stronger the burnout was lower (p=0.005, r=-0.50). A medium-strong, significantly
      negative correlation between the sense of satisfaction and self-realization and
      the burnout level was found--as the satisfaction level increased the burnout
      level decreased. A negative correlation, but a less intense relationship, was
      found between the sense of responsibility and the burnout level (p < 0.05).
      CONCLUSIONS: The findings of this research study show that the TC's sense of
      control and autonomy has a significant role in the prevention of burnout. The
      medical organization's management should be aware and sensitive to these facts in
      order to improve the work of the TC and to prevent job turnover. Lowering the
      burnout rate will hopefully lead to more organ donations and more lives saved.

PMID- 16900739
TI  - [Residents' restricted hours of duty--who will benefit from it: patients, society
      or the physicians?].

PMID- 16900740
TI  - [Interns: the relationship between sleep deprivation, working hours and
      performance].
AB  - In recent years numerous studies were published on the relationship between
      working hours, sleep deprivation and medical errors, clinical judgement,
      attention and motor vehicle accidents. This article reviews the latest literature
      on interns and the implications of continuous working hours, without sleep.
      Current policy changes in the realm of working hours and rest, both in Israel and
      throughout the world, are reviewed.

PMID- 16900741
TI  - [Umbilical metastasis: Sister Mary Joseph's nodule].
AB  - Sister Mary Joseph (1856-1939), who was superintendent nurse at St. Mary's
      Hospital in Rochester, Minnesota, U.S.A. (at present Mayo Clinic), observed that
      patients with intra-abdominal or pelvic malignancy often had an umbilical nodule.
      In 1949 the English surgeon Hamilton Bailey, in his famous textbook
      "Demonstrations of Physical Signs in Clinical Surgery", coined the term "Sister
      Joseph's nodule" for umbilical metastases. To date, more than 400 cases of Sister
      Mary Joseph's nodule have been described in the literature. The nodule may be
      painful and ulcerated, sometimes with pus, blood, or serous fluid. It is usually
      a firm nodule measuring 0.5-2 cm, although some nodules may reach up to 10 cm in
      size. Tumor may spread to the umbilicus through lymph ducts, blood vessels,
      contiguous extension, and embryologic remnants. Sister Mary Joseph's nodule can
      be the first manifestation of an underlying malignancy or an indication of a
      recurrence in a patient with a previous malignancy. The most common origin of
      Sister Mary Joseph's nodule in women is ovarian carcinoma and in men--gastric
      carcinoma. Sister Mary Joseph's nodule has traditionally been considered a sign
      of advanced primary malignancy with an associated poor prognosis; the average
      survival time has been reported to be 11 months with < 15% of the patients
      surviving >2 years. In some patients, however, depending on the state of the
      primary neoplasm and the patient's general condition, surgery and/or chemotherapy
      may improve survival.

PMID- 16900742
TI  - [Drug treatment for children with cerebral palsy].
AB  - Cerebral palsy is the main cause of immobility in children. This motor
      dysfunction is caused by several motor components such as weakness, lack of motor
      control and muscle hypertonia. Drug treatment, delineated in this review, mainly
      addresses the latter. Recently, new definitions for clinical features of
      hypertonia in children were published, assisting the distinction between the two
      common motor symptoms in cerebral palsy, spasticity and dystonia. The main
      functional symptoms disrupt functional daily life, dictating the overall approach
      and the specific drug treatment. There are an increasing number of treatments for
      this distressing disorder. For general spasticity, treatments provided include
      Baclofen. If symptoms are local, either dystonia, or spasticity, Botulinum toxin
      is the revolutionary drug used with significant success and relatively few side
      effects. For generalized dystonia, a trial of both Dopamine and Trihexyphenidyl
      should be considered. Cerebral palsy, like other complex disorders, requires
      individualized decision-making and a team approach. Drug therapy is only one
      aspect of treatment, yet sometimes it may serve as a window of opportunity to
      facilitate better motor control.

PMID- 16900743
TI  - [Transgenerational effects of parental exposure to ionizing radiation].
AB  - The deleterious effects of exposure to ionizing radiation on human health have
      been known for many years. The main long term effect of this exposure is an
      increase in the risk for developing benign and malignant tumors in the exposed
      population. This review summarizes the existing data on the possible effects of
      ionizing radiation on the second generation, focusing on cancer risk. The two
      mechanisms through which parents' exposure to radiation could affect their
      children's health are intrauterine exposure of the fetus and preconception
      exposure of the gonads. Intrauterine exposure to ionizing radiation has
      teratogenic and carcinogenic effects. Most case-control studies have shown a 40
      50% increase in the risk of cancer following intrauterine exposure to medical
      diagnostic radiation at doses of 10-20mGy. Results of these studies have greatly
      contributed to the strict radiation protection guidelines at pregnancy existing
      today. Although animal studies have shown that gonadal exposure to high doses can
      cause heritable genetic changes, this effect has not been demonstrated
      unequivocally in epidemiological studies. A case-control study suggested an
      association between preconception irradiation and leukemia/non-Hodgkin's lymphoma
      in children of male workers at a nuclear plant in the UK (the Gardner
      hypothesis). This report generated substantial interest and research; however,
      subsequent occupational studies failed to confirm the association. Negative
      results were also reported in studies of the atomic bomb survivors and survivors
      of childhood cancer. In summary, epidemiological studies do not support the
      association between gonadal exposure to ionizing radiation and the development of
      cancer and other genetic diseases among offspring.

PMID- 16900744
TI  - [The increase in requests for laboratory tests in the community--are there any
      effective intervention programs?].
AB  - In recent years there is a steady increase in requests for laboratory tests by
      primary care physicians. This increase does not necessarily have a diagnostic and
      therapeutic yield. There is a relationship between background characteristics of
      the family physicians and their utilization of laboratory tests. Various studies
      have been conducted in order to understand the physician's motives for ordering
      laboratory tests in attempts to reduce their number. Interventions to reduce
      laboratory test utilization yield different and sometimes opposing results. We
      reviewed the literature dealing with laboratory test utilization and
      interventions to reduce it.

PMID- 16900745
TI  - [Diet or health--the linkage between vegetarianism and anorexia nervosa].
AB  - Vegetarianism in its various forms, is widely encountered in different societies
      all over the world; thus, combining nutritional, social, behavioral and
      psychological aspects. The prevalence of vegetarianism in the western world, as
      well as in Israel, is dealt with in this review. The extent of vegetarianism
      among young patients with eating disorders is much higher than in any other age
      group. Anorexia nervosa patients in Israel admit to be vegetarians in 85% (mean),
      as compared to 65% (mean) in other western countries. The last three decades
      abound with nutritional messages concerning healthy life styles. Food Pyramids
      recommend meat avoidance as a remedy and promise for longevity. This reason for
      abstaining from meat has led to the adoption of vegetarian diets in grownups. All
      age groups have mastered the "Vegi" trend, and mostly young girls. They express
      feelings of disgust especially towards red meat. Despite the knowledge gained by
      the public about the linkage between diet and health, the proportion of patients
      suffering from eating disorders is rising. There seems to be a direct connection
      between the "Vegi" fashion of the teenagers and eating disorders which start
      typically in adolescence. Many surveys point to the abuse of vegetarianism as a
      mask for weight control. The vegetarian diet, a selective way of eating, might
      precede different eating disorders and increase the risk of developing anorexia
      nervosa.

PMID- 16900746
TI  - [Dr. Henry Wigderson--the first neurosurgeon in Eretz-Israel].
AB  - The vision of Hadassah Medical Organization and the Hebrew University in
      Jerusalem was to establish a University Hospital where clinical excellence and
      high academic level will be the hallmark of its departments. More than seventy
      years ago, guided by this spirit, the leaders of the two institutions attempted
      to establish a department of neurosurgery, which, at the time in only a few
      countries, was making its initial steps as an independent discipline. It was only
      during World War II that Hadassah could bring over a specialist in neurosurgery
      who worked for nearly three years in the Hadassah Hospital on Mount Scopus. This
      article describes the way Dr. Henry Wigderson was selected to be the first
      neurosurgeon in Eretz-Israel, his activities and the incorporation of the idea,
      in spite of the disappointment caused by his departure, that even at times of
      distress, neurosurgery is not a luxury but an indispensable part of an forward
      looking medical institution.

PMID- 16900747
TI  - [The International Conference for Occupational Health ICORD, Beijing 2005].

PMID- 16900748
TI  - [The International Conference for Health Technology Assessment, (Bringing HTA
      Into Practice) Rome, June 2005].

PMID- 16900749
TI  - Fatigue is intrinsic to multiple sclerosis (MS) and is the most commonly reported
      symptom of the disease.

PMID- 16900750
TI  - Myelin oligodendrocyte glycoprotein-induced experimental autoimmune
      encephalomyelitis in the common marmoset reflects the immunopathology of pattern
      II multiple sclerosis lesions.
AB  - Pathomorphological studies described pathological heterogeneity in patients with
      multiple sclerosis (MS). Different effector mechanisms might therefore be
      responsible for lesion formation in MS. The present report shows that myelin
      oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune
      encephalomyelitis (EAE) in common marmoset monkeys reflects one specific lesional
      subtype of MS, namely MS pattern II lesions with antibody/complement-mediated
      damage. MOG-induced EAE in marmoset monkeys will, therefore, provide an ideal
      model for therapeutic approaches directed against B-cell/antibody/complement in
      MS.

PMID- 16900751
TI  - Upregulation of ADAM-17 expression in active lesions in multiple sclerosis.
AB  - ADAM-17, a disintegrin and metalloproteinase, is the major proteinase responsible
      for the cleavage of membrane-bound tumour necrosis factor (TNF) as well as being
      an active sheddase of other cytokines, cytokine receptors, growth factors and
      adhesion molecules. TNF is a major proinflammatory cytokine that has been
      identified as having a pathogenic role in inflammatory diseases within the CNS
      including multiple sclerosis (MS). Here we report the cellular origin and
      distribution of ADAM-17 expression within clinically and neuropathologically
      confirmed MS and normal control white matter, assessed by immunohistochemistry,
      western blotting and PCR. ADAM-17 expression was associated with the blood vessel
      endothelium, activated macrophages/microglia and parenchymal astrocytes in MS
      white matter. Increased levels of ADAM-17 immunoreactivity were displayed in
      active lesions with evidence of recent myelin breakdown. Further studies into the
      functional role of ADAM-17 in the pathogenesis of MS and other inflammatory
      conditions are required.

PMID- 16900752
TI  - Expression of ADAMTS-1, -4, -5 and TIMP-3 in normal and multiple sclerosis CNS
      white matter.
AB  - ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) -1, -4
      and -5 proteases have been identified in the CNS at the mRNA level. These
      glutamyl endopeptidases, inhibited by tissue inhibitor of metalloproteinases
      (TIMP)-3, are key enzymes in the degradation of the aggregating chondroitin
      sulphate proteoglycans (CSPGs), and may therefore play a role in CNS
      extracellular matrix (ECM) changes in multiple sclerosis (MS). We have
      investigated ADAMTS and TIMP-3 expression in normal and MS CNS white matter by
      real-time RT-PCR, western blotting and immunohistochemistry. We report for the
      first time the presence of ADAMTS-1, -4 and -5 in normal and MS white matter.
      Levels of ADAMTS-1 and -5 mRNA were decreased in MS compared to normal tissue,
      with no significant change in ADAMTS-4 mRNA levels. Protein levels of ADAMTS-4
      were significantly higher in MS tissue compared to normal tissue.
      Immunohistochemical studies demonstrated that ADAMTS-4 was associated
      predominantly with astrocytes with increased expression within MS lesions. TIMP-3
      mRNA was significantly decreased in MS compared to controls. These studies
      suggest a role for ADAMTS-4 in the pathogenesis of MS. Further studies on the
      activity of ADAMTS-4 will enable a better understanding of its role in the
      turnover of the ECM of white matter in MS.

PMID- 16900753
TI  - Chlamydia pneumoniae infection and the risk of multiple sclerosis: a meta
      analysis.
AB  - We conducted a meta-analysis of studies comparing the presence of Chlamydia
      pneumoniae (Cpn) between multiple sclerosis (MS) patients and other neurological
      diseases patients or healthy controls. We identified 26 studies with 1332 MS
      patients and 1464 controls. Using random-effects methods, MS patients were found
      more likely to have detectable levels of Cpn DNA (OR = 3.216; 95% CI: 1.204,
      8.585) in their cerebrospinal fluid, and intrathecally synthesized
      immunoglobulins (OR = 3.842; 95% CI: 1.317, 11.212), compared to other patients
      with neurological diseases. There is no evidence for increased levels of serum
      immunoglobulins (OR = 1.068; 95% CI: 0.745, 1.530), even though this result is
      confounded by the presence of studies using normal subjects as controls.
      Similarly, there is no evidence for association of immunoglobulins against Cpn in
      the cerebrospinal fluid (OR = 3.815; 95% CI: 0.715, 20.369). Up to 59.7% of the
      between-studies variability could be explained by the inappropriate matching of
      cases and controls for gender. In random-effects meta-regressions, adjusting for
      the confounding effect of gender differences results in stronger and
      statistically significant associations of MS with detectable levels of Cpn DNA,
      intrathecally synthesized immunoglobulins and immunoglobulins in the
      cerebrospinal fluid. Even though the presence of Cpn is clearly more likely in MS
      patients, these findings are insufficient to establish an etiologic relation.

PMID- 16900754
TI  - Myelin basic protein and myelin oligodendrocyte glycoprotein T-cell repertoire in
      childhood and juvenile multiple sclerosis.
AB  - Multiple sclerosis (MS) is usually a disease of young adulthood, its clinical
      onset occurring between 20 and 40 years of age; however, today there is general
      consensus that MS can also occur in children, adolescents and even in infants. In
      order to gain further insight into the T-cell repertoire present in this
      particular group of patients myelin basic protein (MBP)-, MBP exon-2- and myelin
      oligodendrocyte glycoprotein (MOG)Igd-specific T-cell lines (TCLs) were isolated
      from 18 patients whose symptoms had started before the age of 16. Epitope
      specificity was established by measuring proliferative responses, and interferon
      y (IFN-y) secretion by using a panel of overlapping synthetic peptides. For
      MOGIgd, the T-cell response was focused on three main immunodominant epitopes
      comprising residues 1-26, 36-60 and 63-87. For MBP the predominant immune
      responses were directed against peptides 83-102, 139-153 and 146-162. When
      compared to those observed in adult-onset MS patients, anti-MOGIgd specificity
      and anti-MBP responses showed similar results. Moreover, the number of MBP exon-2
      TCLs isolated, and the magnitude of the specific IFN-gamma secretion induced were
      similar, both in childhood/juvenile-onset and adult-onset MS patients. Thus,
      despite differences in the clinical and neuroimaging manifestations of MS, these
      results would seem to indicate that both the spectrum of MBP found, as well as
      the MOGIgd epitopes recognized by peripheral blood T cells in MS, appear to be
      similar for childhood/juvenile-onset and adult-onset patients.

PMID- 16900756
TI  - Memory performance in multiple sclerosis patients correlates with central brain
      atrophy.
AB  - OBJECTIVE: To assess whole brain and central brain atrophy as well as their
      differential relation to memory, cognitive performance, fatigue, depression and
      quality of life in patients with relapsing-remitting multiple sclerosis (RRMS).
      METHODS: A 3D flow compensated gradient recalled T1-weighted MRI was acquired in
      45 RRMS patients. An automated analysis tool was used to calculate brain
      parenchymal fraction (BPF) and ventricular brain fraction (VF). All patients were
      assessed with neuropsychological tests focusing on memory and self-rating scales
      for depression, fatigue and quality of life. Age corrected partial correlations
      between brain atrophy, motor performance, psychological scales and test scores
      were calculated. RESULTS: BPF correlated moderately (0.3 < or = r < 0.5) with
      duration of symptoms and disease, the Expanded Disability Status Scale (EDSS),
      the upper extremity motor performance, and with mental aspects of quality of
      life. VF correlated moderately with EDSS, upper and lower extremity motor
      performance and memory functions. Neither BPF nor VF correlated with fatigue and
      depression. Results of several cognitive tests correlated moderately with
      depression and fatigue, the Paced Auditory Serial Addition Test (PASAT) showing
      the largest correlation. CONCLUSIONS: Memory performance shows a correlation with
      relative ventricular size in RRMS patients, indicating the strategic location of
      the ventricle system along the structures of the limbic system and its
      vulnerability in MS. The PASAT and several other cognitive tests show moderate
      correlations with depression and fatigue, arguing for an inter relation between
      the cognitive functioning and the emotional state of patients. However, this
      relation is independent of measurable brain atrophy.

PMID- 16900755
TI  - Variations in chemokine receptor and cytokine expression during pregnancy in
      multiple sclerosis patients.
AB  - Although several T cell-mediated autoimmune diseases have shown a reduction in
      their clinical disease activity during pregnancy, the underlying mechanisms by
      which pregnancy causes such a beneficial effect on the disease activity are not
      fully understood. We performed a longitudinal study of chemokine receptors (CCR3,
      CCR4, CCRS, CXCR3, CXCR4) by flow cytometry in different subsets of peripheral
      blood mononuclear cells (PBMC) during pregnancy in multiple sclerosis (MS)
      patients. The levels of cytokine mRNA expression (IL-10, IFN-gamma) were also
      investigated by real-time quantitative reverse transcription polymerase chain
      reaction. The expression of CXCR3 by CD4 and CD8 positive T cells was decreased
      to a statistically significant extent during the second trimester of pregnancy.
      CD4 and CD8 T cells showed a statistically significant increase in the expression
      of CXCR4 during the third trimester of pregnancy. At the mRNA expression level,
      an increase in the IL-10/IFN-gamma ratio was observed during pregnancy,
      especially during the third trimester. These findings indicate immunomodulatory
      effects of pregnancy on the expression of chemokine receptors and cytokines,
      which may be related to changes in the clinical disease activity of T cell
      mediated autoimmune diseases, such as MS.

PMID- 16900757
TI  - Cognitive impairment is associated with subcortical magnetic resonance imaging
      grey matter T2 hypointensity in multiple sclerosis.
AB  - Grey matter hypointensity on T2-weighted magnetic resonance imaging (MRI) scans,
      suggesting iron deposition, has been described in multiple sclerosis (MS) and is
      related to physical disability, disease course and brain atrophy. We tested the
      hypothesis that subcortical grey matter T2 hypointensity is related to cognitive
      impairment after adjusting for the effect of MRI lesion and atrophy measures. We
      studied 33 patients with MS and 14 healthy controls. Normalized T2 signal
      intensity in the caudate, putamen, globus pallidus and thalamus, total brain T1
      hypointense lesion volume (T1LV), fluid-attenuated inversion-recovery
      hyperintense lesion volume (FLLV) and brain parenchymal fraction (BPF) were
      obtained quantitatively. A neuropsychological composite score (NCS) encompassed
      new learning, attention, working memory, spatial processing and executive
      function. In each of the regions of interest, the normalized T2 intensity was
      lower in the MS versus control group (all P<0.001). Regression modelling tested
      the relative association between all MRI variables and NCS. Globus pallidus T2
      hypointensity was the only variable selected in the final model (R2 = 0.301, P =
      0.007). Pearson correlations between MRI and NCS were T1LV: r = -0.319; FLLV: r =
      -0.347; BPF: r = 0.374; T2 hypointensity of the caudate: r = 0.305; globus
      pallidus: r = 0.395; putamen: r = 0.321; and thalamus: r = 0.265. Basal ganglia
      T2 hypointensity and BPF demonstrated the strongest associations with cognitive
      impairment on individual cognitive subtests. Subcortical grey matter T2
      hypointensity is related to cognitive impairment in MS, supporting the clinical
      relevance of T2 hypointensity as a biological marker of MS tissue damage. These
      data implicate a role for basal ganglia iron deposition in neuropsychological
      dysfunction.

PMID- 16900758
TI  - How to detect cognitive dysfunction at early stages of multiple sclerosis?
AB  - Detecting cognitive dysfunction may be clinically important during the early
      stages of multiple sclerosis (MS). We assessed a self-report questionnaire on
      cognitive complaints and individual neuropsychological tests to select patients
      with early relapsing-remitting MS (RRMS) who needed comprehensive cognitive
      testing. Fifty-seven patients underwent neurological and neuropsychological
      assessment, including Rao's Brief Repeatable Battery (BRB) and the complete SEP
      59 Questionnaire, a French adaptation of the MSQOL-54, which contains four
      specific questions about self-perception of cognitive functions. Predictive
      values, specificity, sensitivity and accuracy of five individual
      neuropsychological tests--Selective Reminding Test, Symbol Digit Modalities Test
      (SDMT), Similarities Subtest, PASAT and Stroop Test--were calculated to predict
      cognitive impairment. Only 10.5% of patients did not report any cognitive
      complaint, while most reported complaints. On the basis of cognitive
      performances, 59.7% of patients were classified as cognitively impaired, although
      only one cognitive score was correlated with cognitive complaints. Depressive
      symptoms and fatigue were associated with more cognitive complaints. Sensitivity
      of the SDMT to predict cognitive impairment was 74.2%, specificity was 76.9% and
      accuracy was 75.4%. Since, at this stage, patients' cognitive complaints are
      already influenced by depression and fatigue and do not accurately reflect
      cognitive performances, the SDMT may help to select patients for testing with a
      more complete cognitive battery.

PMID- 16900759
TI  - Relationship between stress and relapse in multiple sclerosis: Part I. Important
      features.
AB  - OBJECTIVE: The aim of this two-year prospective study was to examine the
      relationship between multiple aspects of life-event stress and relapse in
      multiple sclerosis (MS) patients. BACKGROUND: Few studies have defined the
      critical features of this life-event stress; for example, stressor duration,
      frequency, severity, disease-dependency, valency, or stressor constructs, such as
      the propensity to cause emotional distress/threat or the frustration of life
      goals. METHODS: 101 consecutive participants with MS were recruited from two MS
      clinics in Sydney, Australia. Stressful life events were assessed at study-entry
      and at three-monthly intervals for two years. Patient-reported relapses were
      recorded and corroborated by neurologists or evaluated against accepted relapse
      criteria. RESULTS: Acute events, but not chronic difficulties (CDs), predicted
      relapse occurrence: acute stressor frequency counts predicted greater relapse
      risk, along with low disability score (EDSS) and being male. We also confirmed
      the bi-directional stress-illness hypothesis: stressors predicted relapse, and
      relapse separately predicted stressors. CONCLUSIONS: Life-event stress impacts to
      a small degree on MS relapse. The number and not the severity of acute stressors
      are most important; chronic stressors do not predict later relapse. Males and
      those with early stage disease are also at greater risk of relapse. MS patients
      should be encouraged to reduce acute stressors during times of high stress, and
      feel reassured that disease-related chronic stressors do not increase their
      relapse risk.

PMID- 16900760
TI  - Relationship between stress and relapse in multiple sclerosis: Part II. Direct
      and indirect relationships.
AB  - OBJECTIVE: The aim of this two-year prospective study was to determine which
      factors were: (i) directly related and/or (ii) indirectly related to multiple
      sclerosis (MS) relapse. These factors included life-event stressors, disease,
      demographic, psychosocial and lifestyle factors. BACKGROUND: Relatively little
      attention has been paid to the role of non-clinical relapse predictors (other
      than stressful life-events) in MS, or factors that indirectly impact on the
      stress-relapse relationship. METHODS: A total of 101 consecutive participants
      with MS were recruited from two MS clinics in Sydney, Australia. Stressful life
      events, depression, anxiety and fatigue were assessed at study-entry and at three
      monthly intervals for two years. Disease, demographic, psychosocial and lifestyle
      factors were assessed at baseline. Patient-reported relapses were recorded and
      corroborated by neurologists or evaluated against accepted relapse criteria.
      RESULTS: MS relapse was predicted by acute stressor frequency counts, coping
      responses that utilized social support, and being born in Australia, but not by
      chronic stressors, disease, demographic, psychosocial or lifestyle factors. No
      factors were found to indirectly impact on the stress relapse relationship.
      CONCLUSIONS: The number rather than severity of stressors was most important in
      relation to MS relapse risk, along with coping responses that utilized social
      support, suggesting that MS patients should avoid situations that are likely to
      generate multiple stressors or which provide few avenues for social support.

PMID- 16900761
TI  - Interferon treatment may trigger primary headaches in multiple sclerosis
      patients.
AB  - Recent data have suggested that interferon-beta (IFN-beta) may aggravate
      headaches in multiple sclerosis (MS) patients. The aim of this study was to
      investigate the life-time prevalence of primary headaches in MS patients treated
      with interferons in comparison with patients treated with other disease-modifying
      agents. Attention was focused on the onset of headache and the changes in pre
      existing headaches in relation to the onset of therapy. The study was open
      labelled and not randomized. We studied 150 consecutive MS patients treated with
      IFN-beta (109 patients: 54 with 1b, 55 with 1a) and with other drugs (41
      patients: 14 with glatiramer acetate, 27 with azathioprine). All patients
      underwent a semi-structured interview to diagnose headache type, according to the
      International Headache Society criteria. The frequency of primary headaches was
      higher in the interferon-group (72%) compared to patients in the other group
      (54%) (P=0.03). Worsening of pre-existing headaches or development of de novo
      headache occurred only in the interferon-group (41 and 48%, respectively) and not
      in the other group (P<0.001). These results show that headache should be
      considered among the side-effects of interferon in MS patients.

PMID- 16900762
TI  - Sleep and fatigue in multiple sclerosis.
AB  - Fatigue is common in multiple sclerosis (MS) and is an important cause of
      disability. However, the cause of fatigue is poorly understood. This study aimed
      to describe the frequency and pattern of sleep disturbance in a group of
      outpatients with MS, and to investigate the relationship between sleep
      disturbance and fatigue. Sixty outpatients with MS completed the Fatigue Severity
      Scale (FSS) and the Epworth Sleepiness Scale and kept a sleep diary for seven
      days. Fatigue and excessive daytime sleepiness were common in this group of
      patients (64 and 32%). Sleep problems on at least two nights per week occurred
      frequently, including initial insomnia in 42%, middle insomnia in 53% and
      terminal insomnia in 58%. The reasons cited for different types of insomnia
      varied, with anxiety and pain/discomfort being the commonest causes of initial
      insomnia and nocturia the commonest cause of middle insomnia. Middle insomnia was
      significantly correlated with daytime fatigue, a relationship that remained after
      controlling for disability. Sleep disturbance is common in MS and is associated
      with treatable symptoms, including pain and nocturia. Sleep disturbance may be an
      important factor contributing to fatigue in patients with MS.

PMID- 16900763
TI  - Fatigue in progressive multiple sclerosis is associated with low levels of
      dehydroepiandrosterone.
AB  - BACKGROUND AND OBJECTIVE: Fatigue is one of the most limiting symptoms in
      multiple sclerosis (MS) and the mechanisms underlying its origin are poorly
      understood. Our aim was to test whether fatigue in MS is associated with
      endocrine markers. METHODS: We longitudinally studied 73 progressive MS patients.
      Fatigue was assessed at baseline and at 3, 6, 12 and 24 months using the Fatigue
      Severity Scale (FSS). Given the longitudinal design of our study, patients were
      labelled as sustained fatigued when FSS scores were >5.0 at all time points, and
      as non-fatigued when FSS scores were < or = 5.0 at all time points. Serum levels
      of dehydroepiandrosterone (DHEA), its sulphated conjugate (DHEAS) and cortisol
      were measured at each time point. RESULTS: Twenty-nine patients scored >5.0 in
      the FSS at all time points, and 9 patients (12.3%) scored 5.0 at all time points.
      Mean baseline levels of DHEAS and DHEA were lower in MS patients with sustained
      fatigue when compared to patients without fatigue (P = 0.01 and P = 0.03
      respectively). Analysis of DHEAS and DHEA over time showed significantly lower
      hormone levels in patients with fatigue [F(1,31) = 6.14, P=0.019 for DHEAS;
      F(1,32) = 6.63, P=0.015 for DHEA]. CONCLUSIONS: Fatigue in progressive MS could
      be related to low serum levels of DHEA and DHEAS. Our results suggest that these
      hormones should be considered as biological markers of fatigue in MS patients and
      that hormone replacement may thus be tested as an option to treat fatigue in MS
      patients.

PMID- 16900764
TI  - The six spot step test: a new measurement for walking ability in multiple
      sclerosis.
AB  - OBJECTIVE: The primary objective of this study was to develop a quantitative test
      to assess ambulation in multiple sclerosis (MS) patients that is more accurate
      and sensitive than the Timed 25-foot walk (T25FW). For this purpose, we developed
      the Six Spot Step Test (SSST), which besides speed includes co-ordination and
      balance, to be a lower limb counterpart to the 9-Hole Peg Test (9HPT).
      BACKGROUND: The T25FW, which is the ambulation test of the MS Functional
      Composite (MSFC), reflects only the speed component of walking. The lack of
      sensitivity to other components of gait adds to the floor effect. METHODS AND
      PATIENTS: In the SSST, the patient is instructed to walk as quickly as possible
      from one end to the other of a rectangular field measuring 1 x 5 m, while kicking
      five cylinder blocks out of five circles marked on the floor. Some 151 MS
      patients with the Expanded Disability Status Scale (EDSS) score 0-6.5 and 64
      normal controls performed the SSST and the T25FW. In addition, 41 patients
      performed the tests twice. RESULTS: The range of the SSST (4.7-35.1 seconds) was
      wider than that of the T25FW (3.5-22.6 seconds). Using control mean + 2 SD as cut
      off, 107 patients had abnormal SSST, while 100 patients had abnormal T25FW. The
      T25FW (mean) increased 2.1 seconds over the EDSS range of 0-4.0, while the SSST
      increased 4.9 seconds. The intra-class correlation between repeated tests (r) was
      0.95 for the SSST and 0.96 for the T25FW. The correlation between the SSST and
      the T25FW was high (r=0.92). CONCLUSION: The SSST seems to be superior to the
      T25FW in terms of dynamic range, floor effect and discriminatory power. The SSST
      is a relevant alternative for the T25FW as the ambulation component of the MSFC.

PMID- 16900765
TI  - Clinical characteristics of multiple sclerosis in Taiwan: a cross-sectional
      study.
AB  - This study reviewed the clinical characteristics of multiple sclerosis (MS) in
      Taiwanese patients from 1993 to 2001. Of the 75 MS patients with a mean age of
      onset of 35.6 +/- 12.6 years, the female-to-male ratio was 4.4 (61/14). In 42
      (56%) optico-spinal MS (OS-MS) patients, the age of onset (37.6 +/- 11.1 years)
      tended to be older than conventional MS (C-MS) patients (33.1 +/- 14.1 years, P =
      0.08). In 60 cerebrospinal fluid (CSF) specimens, raised IgG index (>0.7) and
      oligoclonal bands were noted in 26 (43.3%) and two (3.3%) cases, respectively.
      The frequency of raised IgG index was lower in OS-MS (31.3%) than in C-MS (57.1%,
      P = 0.07). The CSF total protein concentrations were significantly higher in OS
      MS (64.5 mg/dL) than in C-MS (46.6 mg/dL, P = 0.047). The mean annual relapse
      rate was 54.1%, and was significantly higher within the first year (59.7%, P <
      0.001). The mean annual relapse rate in OS-MS (62.7%) was significantly higher
      than in C-MS (41.2%, P=0.01). The differences in the annual relapse rate and
      total protein concentration in CSF between OS-MS and C-MS suggest probably two
      distinct immunopathogenesis. The higher first year relapse rate of MS patients in
      Taiwan may address the importance of early intervention with immunomodulatory
      therapy.

PMID- 16900766
TI  - A systematic review of oral methotrexate for multiple sclerosis.
AB  - Oral methotrexate is a potent immunosuppressant, which could have a beneficial
      effect on relapse rates and delay disease progression in multiple sclerosis (MS).
      We performed a systematic review of all randomized controlled trials of oral
      methotrexate for MS. Of the two randomized controlled trials identified, one was
      excluded due to its allocation concealment and definition of a relapse and time
      to sustained disease progression. The other trial studied 60 participants with
      progressive MS only. This trial reported a non-significant reduction in sustained
      Expanded Disability Status Scale (EDSS) progression and number of relapses in
      favour of methotrexate therapy. There were no data on relapse rate and no
      difference in time to first relapse. Minor side-effects were reported in both
      methotrexate (87.1%) and placebo groups (89.7%), but there were no major side
      effects. Further trials are required in both relapsing-remitting and progressive
      groups to establish the role of oral methotrexate in MS.

PMID- 16900767
TI  - CD24 V/V is an allele associated with the risk of developing multiple sclerosis
      in the Spanish population.
AB  - The allele C in the CD24 gene has been related to multiple sclerosis (MS). In
      this work we check this single nucleotide polymorphism (SNP) in a population of
      135 patients and 285 controls. Our results confirm the association between the
      V/V genotype at aa 57 of this gene and MS and highlight the importance of taking
      into account the origin of the subjects to avoid a population bias.

PMID- 16900768
TI  - Periodic hyperthermia and abnormal circadian temperature rhythm in a patient with
      multiple sclerosis.
AB  - Disturbances of the central thermoregulation in patients with multiple sclerosis
      (MS) are not often reported. We describe a 45-year old patient with a 13-year
      history of MS, who developed a clinical picture of recurrent hyperthermia. MRI
      showed a bilateral involvement of the hypothalamus in the setting of diffuse
      white matter disease. Serial body temperature measurement for five consecutive
      months disclosed an inversion of the circadian temperature rhythm. The clinical
      presentation and MRI findings suggested abnormalities of the central thermal
      control in relation to MS widespread involvement of the central nervous system
      (CNS).

PMID- 16900769
TI  - Aphasia and multiple sclerosis.

PMID- 16900770
TI  - Early abnormalities in evoked potentials and future disability in patients with
      multiple sclerosis.

PMID- 16900771
TI  - Bone marrow from CD18-/- (MAC-1-/-) homozygous deletion recombinant negative mice
      demonstrates increased longevity in long-term bone marrow culture and decreased
      contribution to irradiation pulmonary damage.
AB  - BACKGROUND: Bone marrow macrophage surface expression of CD18 (MAC-1, LFA1) is
      involved in cellular binding to V-CAM-1 and V-CAM-2 adhesion molecules expressed
      on endothelial cells. We sought to determine if this interaction affected the
      growth of marrow in long-term bone marrow cultures (LTBMCs) and macrophage
      migration to the irradiated lung in pulmonary fibrosis/organizing alveolitis.
      MATERIALS AND METHODS: Continuous bone marrow cultures from CD18-/- and CD18+/+
      littermates were established. Bone marrow migration to the irradiated lung was
      quantitated in CD18+/+ or CD18-/- marrow chimeric mice. Anti-macrophage
      antibodies were administered to block monocyte/macrophage migration after lung
      irradiation. RESULTS: CD18-/- LTBMCs demonstrated significantly increased
      longevity (over 20 weeks) of production of multilineage hematopoietic progenitor
      cells, total non-adherent cells and macrophage progenitors compared to those
      derived from CD18+/+ littermates (10 weeks). C57BL/6J female mice chimeric for
      male CD18-/- bone marrow showed improved (50%) survival at 120 days after
      pulmonary radiation compared to female mice chimeric for male CD18+/+ bone marrow
      (0.0%). Intraperitoneal injections (daily for 15 days) of an anti-macrophage
      antibody on days 80-98 after 20 Gy total lung irradiation resulted in reduction
      of macrophage migration to the lungs and increased survival. CONCLUSION: The data
      demonstrate a complex role of CD18 (MAC-1) in macrophage progenitor and
      macrophage cellular interaction involving stromal cells of the bone marrow and
      lung.

PMID- 16900772
TI  - Suppressive effect of fluticasone propionate on MMP expression in the nasal
      mucosa of allergic rhinitis patients in vivo.
AB  - The effects of intranasal corticosteroids on matrix metalloproteinases (MMPs) and
      their inhibitors (tissue inhibitors of metalloproteinases (TIMPs)) in the nasal
      mucosa of patients with allergic rhinitis (AR) are not known. Nasal mucosa biopsy
      specimens were obtained from AR patients, with or without the administration of
      fluticasone propionate (FP) nose drops, and from healthy volunteers as controls.
      The specimens were analyzed by immuno-histochemistry and ELISA for MMP-2, MMP-9,
      TIMP-1 and TIMP-2. The MMP-9 levels in nasal mucosa extracts in the AR patients
      were significantly higher than in the controls. A significant suppressive effect
      of FP on the MMP-9 levels was shown. The control subjects showed no MMP- or TIMP
      positive cells, whereas such positive cells were clearly present in the AR
      patients. No MMP- or TIMP-positive cells were detected after topical application
      of FP. These results suggest that the suppressive effect of FP on MMP expression
      is, in part, responsible for its clinical efficacy in AR.

PMID- 16900773
TI  - A quantitative approach to the free radical interaction between alpha-tocopherol
      or ascorbate and flavonoids.
AB  - Despite numerous previous studies, the mechanism of the free radical interaction
      between alpha-tocopherol (VE), or ascorbate and flavonoids, as coantioxidants
      remains unclear. The synergistic antioxidant effects of VE or L-ascorbyl 2,6
      dibutyrate (ASDB, an ascorbate derivative) with the flavonoids (-)-epicatechin
      (EC), (-)-epigallocatechin (EGC), (-)-epicatechin gallate (ECG) and (-)
      epigallocatechin gallate (EGCG) and methyl gallate (MG), were investigated by the
      induction period method in the polymerization of methyl methacrylate (MMA),
      initiated by thermal decomposition of 2,2'-azobis(isobutyronitrile) (an alkyl
      radical, R *), under nearly anaerobic conditions. For VE, a synergistic
      antioxidant effect was observed with MG, EC, EGC and ECG, whereas this activity
      was decreased by the addition of EGCG. For ASDB, a synergistic antioxidant effect
      was observed with EGC and ECG, whereas this activity was decreased by the
      addition of EGCG or MG. A synergistic antioxidant effect (regeneration of VE)
      appears to be feasible even though the BDE (phenolic O-H bond dissociation
      entropy) of the coantioxidants is significantly higher than that of VE. The
      driving force for the regeneration process may be the removal of the semiquinone
      radical from the flavonoids MG, EC, EGC and ECG by the VE radical. In the
      ASDB/flavonoid mixture, flavonoid radicals are scavenged by ASDB. The partial
      regeneration of flavonoids by ASDB may follow a similar recycling mechanism to
      that of the well-known VE/ascorbate mixture. The free radical interaction between
      EGCG and VE or ASDB decreased the antioxidant effect. Such enhancement of
      prooxidation in EGCG/VE or EGCG/ASDB mixtures oxidized by R * may increase their
      cytotoxic effects.

PMID- 16900774
TI  - Inhibition of large intestinal cancers by celecoxib using a serial sacrifice
      technique.
AB  - In this serial sacrifice experiment, celecoxib (C) was administered at a 0.1%
      dose level, in the diet of female Swiss Webster CFW outbred mice. The animals
      also received either 1,2-dimethylhydrazine dihydrochloride (1,2-DMH) as ten
      weekly subcutaneous (s.c.) injections at 20 microg/g body weight or physiological
      saline (PS) as ten weekly s.c. injections at 0.01 ml/g body weight. Subsequently,
      the mice were sacrificed at 26 weeks or 35 weeks after the first injection of 1,2
      DMH or PS. The number of mice with large intestinal tumors and the total number
      of these tumors were: Group 1 (1,2-DMH), 29 and 438; Group 2 (C + 1,2-DMH), 18
      and 64; and Group 3 (PS), 1 and 1, in the mice sacrificed at 26 weeks. The
      corresponding tumor incidences in the mice sacrificed at 35 weeks were: Group 1
      (1,2-DMH), 30 and 323; Group 2 (C + 1,2-DMH), 23 and 134; and Group 3 (PS), 0 and
      0. Histopathologically, the tumors were diagnosed as polypoid adenomas and
      adenocarcinomas of the cecum, colon and rectum. Celecoxib treatment inhibited the
      development of large intestinal cancers in mice sacrificed at 26 or 35 weeks
      after the first injection of the carcinogen.

PMID- 16900775
TI  - The effects of enalapril on p53 expression in left ventricular cardiomyocytes
      after aortic stenosis.
AB  - ACE-inhibitors prevent the development of left ventricular hypertrophy (LVH). The
      tumor suppressor gene p53 up-regulates the cellular renin-angiotensin system,
      resulting in ANG II synthesis, which activates p53 creating a positive feedback
      loop. One hundred and fourteen rabbits were separated into groups A (control), B
      (sham-operated), C and D. In groups C and D, an aortic stenosis was performed,
      and in group D the animals were treated with enalapril. For p53 determination, LV
      specimens were examined by Western blot analysis and an immunohistochemical study
      was performed, except for samples from group D. In conclusion, LVH was
      significantly induced at 7 and 28 days after aortic stenosis with no difference
      between the two periods, while enalapril prevented hypertrophy in these two
      groups. p53 was transcriptionally activated and immunoreactively present after
      acute pressure overload as well as in the sham-operated group. Enalapril
      decreased the p53 expression at 180 min, 7 and 28 days following aortic stenosis.

PMID- 16900776
TI  - Expression of CYLD, NF-kappaB and NF-kappaB-related factors in salivary gland
      tumors.
AB  - The cylindromatosis (CYLD) gene was originally identified as a tumor suppressor
      that is mutated in familial cylindromatosis, an autosomal dominant condition that
      confers a predisposition to multiple tumors of the skin appendages. CYLD has
      deubiquitinating enzyme activity and inhibits the activation of transcription
      factor NF-kappaB. Therefore, loss of CYLD function correlates with tumorigenesis.
      Expression of CYLD has been detected in various organs, but its expression in
      salivary gland tumor (SGT) is still unknown. Adenoid cystic carcinoma (ACC) is a
      well known and typical malignant SGT ACC was previously known as cylindroma in
      view of its marked histological resemblance to dermal cylindroma. In this study,
      the expressions of CYLD and NF-kappaB mRNA in HSG, a human SGT cell line, were
      found to be increased by TNF-alpha stimulation. Immunohistochemistry clearly
      demonstrated the expression of CYLD and NF-kappaB-related factors in ACC tissue.

PMID- 16900777
TI  - Identification of autosomal supernumerary chromosome markers (SMCs) by
      fluorescent in situ hybridization (FISH).
AB  - Supernumerary marker chromosomes (SMCs) are rare chromosomal abnormalities
      resulting in partial trisomy of specific genomic regions with characteristic
      phenotypic effects. Twenty six cases with autosomal SMCs are reported. Four were
      identified prenatally and 22 postnatally in children, aged from 8 days to 15
      years, who were referred for genetic evaluation because of various congenital
      anomalies and developmental delay. In 22 of the 26 cases, the SMCs were de novo,
      in two they were familial and in another two a 11;22 reciprocal translocation was
      revealed in the mothers. In only one patient was the SMC present in a mosaic
      form. Sequential fluorescent in situ hybridization studies (FISH) using Whole
      Chromosome Paint (WCP) probes were performed in order to determine the
      chromosomal origin of the SMCs. Sixteen of them originated from chromosome 15,
      five were shown to be an isochromosome 18p and one was derived from chromosome
      22, but did not contain the DiGeorge/ VCFS critical region. In two instances, the
      SMCs were derivatives of chromosome 13 and in two the SMCs resulted from a 11;22
      maternal translocation and contained material from both chromosomes 11 and 22.
      Molecular investigation of two of the patients with an SMC[15] revealed three
      copies of the SNRPN gene, but the diagnosis of PW/AS due to possible imprinting
      was excluded in both patients by a methylation-specific PCR. FISH and molecular
      studies have greatly facilitated the characterization of marker chromosomes. As
      more SMCs are classified, better genetic counseling and risk evaluation can be
      achieved.

PMID- 16900778
TI  - The normal human amniotic fluid supernatant proteome.
AB  - Proteomic analysis combining two-dimentional electrophoresis (2DE) and mass
      spectrometry (MS) has the potential for a wide range of applications in
      biological and medical sciences, as protein screening in tissues obtained from
      healthy and diseased conditions can determine drug targets and diagnostic
      markers. Conventionally, amniotic fluid (AF) samples are routinely used for
      prenatal diagnosis of a wide range of fetal abnormalities. Proteomics have
      already been applied in the analysis of tissues from fetuses with Down's
      syndrome, in order to detect differences in their protein profile as compared to
      the normal profiles and to determine possible diagnostic tools. A detailed
      protein 2DE for the normal human AF has not been reported. In the present study,
      the 2D protein database of the normal human AF supernatant (AFS) was constructed.
      Ten AFS samples from women carrying normal fetuses were analysed by 2DE. A mean
      of 412 spots per gel were analyzed and protein identification was carried out by
      MALDI-MS and MALDI-MS-MS. A 2D protein map comprising of 136 different gene
      products was constructed. The majority of the identified proteins are regulatory
      proteins, enzymes, secreted proteins, carriers and immunoglobulins. Twelve
      hypothetical proteins were also included. The normal AFS proteome map is a
      valuable tool for the study of aberrant protein expression and the search for
      proteins as possible markers for the prediction of abnormal fetuses.

PMID- 16900779
TI  - Concentration-dependent effect of Rikko-san on the prostaglandin E2 production by
      mouse macrophage-like cells.
AB  - Rikko-san (RKS) and its ingredients were investigated for their activity to
      stimulate prostaglandin E2 (PGE2) production by unstimulated and
      lipopolysaccharide (LPS)-stimulated mouse macrophage-like Raw 264.7 cells. LPS
      significantly stimulated the production and extracellular secretion of PGE2 by
      Raw 264.7 cells. RKS dose-dependently modified the LPS-stimulated PGE2
      production. A lower concentration (0.04-0.4 mg/ml) of RKS stimulated PGE2
      production without or with LPS, whereas a higher concentration (4 mg/ml) of RKS
      inhibited the LPS-stimulated PGE2 production, suggesting the presence of both
      stimulator(s) and inhibitor(s) for PGE2 production. The inhibitory effect of a
      higher concentration of RKS was slightly neutralized by supplementation of
      exogenous arachidonic acid. Among five RKS ingredients, Kanzo inhibited the LPS
      stimulated PGE2 production to the greatest extent, whereas other ingredients
      (Shoma, Ryutan, Saishin, Bofu) stimulated PGE2 production. Western blot analysis
      demonstrated that RKS and all its ingredients enhanced the intracellular
      concentration of cyclooxygenase-2, whereas RKS did not significantly affect the
      phospholipase A2 protein level. The present study demonstrates that the
      concentration-dependent effect of RKS on the PGE2 production by macrophage cannot
      be explained only by the expression levels of cyclooxygenase-2 or phospholipase
      A2.

PMID- 16900780
TI  - Anti-stress activity of mulberry juice in mice.
AB  - The possible anti-stress activity of mulberry juice was investigated in mice.
      When mice were subjected to water immersion restraint stress at 25 degrees C for
      8 h, the plasma lipid peroxide level, determined by the d-ROMs test performed 12
      h thereafter, was almost doubled. After administration of mulberry juice one or
      two weeks before the stress loading, the lipid peroxidation was completely
      blocked. Administration of mulberry juice after the stress loading, without pre
      administration, was also protective. ESR spectroscopy revealed that mulberry
      juice scavenged superoxide anion (generated by hypoxanthine and xanthine oxidase
      reaction), hydroxyl radical (produced by the Fenton reaction) and NO radical
      (generated by a NO donor) at approximately 50% efficiency of blueberry juice.
      Mulberry juice produced smaller amounts of radical at neutral to alkaline pH. The
      cytotoxic and anti-HIV activities of mulberry juice were 18% and >4-fold those of
      blueberry juice, respectively. These data suggest that the anti-stress activity
      of mulberry juice in vivo may be derived from its radical scavenging activity.

PMID- 16900781
TI  - Aloe-emodin affects the levels of cytokines and functions of leukocytes from
      Sprague-Dawley rats.
AB  - Aloe-emodin has shown anti-neoplastic activity against some human cancer cell
      lines. This study aimed to explore the effects of aloe-emodin on the phagocytosis
      of macrophages, the activity of natural killer (NK) cells and the expression of
      cytokines in leukocytes from Sprague-Dawley rats. Leukocytes were collected,
      placed into culture plates and the functions of macrophages and NK cells and the
      percentage of viable cells were determined by flow cytometric analysis.
      Incubation of leukocytes with various concentrations of aloe-emodin caused a dose
      dependent decrease of viable cells, a decrease of phagocytosis by macrophages,
      and a decrease of the activity of NK cells. Evaluation of cytokines in leukocytes
      by ELISA indicated that aloe-emodin increased the levels of interleukin (IL)
      1beta and tumor necrosis factor (TNF)-alpha. The results were also confirmed by
      PCR assay for the mRNA expression of the examined cytokines.

PMID- 16900782
TI  - Up-regulation of VEGF expression and related neo-angiogenesis in childhood high
      grade gliomas: implications for anti-angiogenic anti-neoplastic therapy.
AB  - Vascular endothelial growth factor (VEGF) is a homodimeric, disulfide-linked
      glycoprotein which exhibits endothelial cell-specific mitogenic properties. VEGF
      is also a potent inducer of vascular permeability. There is considerable
      experimental evidence that VEGF isoforms are strongly involved in provoking
      neoangiogenesis of neoplastic cells and, consequently, the growth and progression
      of primary neoplasms (i.e., astrocytic gliomas), including the formation of an
      invasive and metastatic immunophenotype (IP). During this immunohistochemical
      study, the presence and tissue localization of VEGF121 was observed in
      anaplastic, high-grade astrocytomas (AAs) and in glioblastoma multiforme (GBMs)
      employing the specific monoclonal antibody against it. A sensitive, four-step,
      alkaline phosphatase-conjugated antigen detection technique was used. The
      immunoreactivity demonstrated a cytoplasmic, cell surface and extracellular
      matrix localization pattern in more than 90% of the tumor cells, with high
      intensity immunoreactivity (++++, A,B) in every high-grade astrocytic glioma
      tissue. VEGF121 expression was identified mostly within the cytoplasm of tumor
      cells, suggesting an embryonic, undifferentiated and more malignant cellular IP
      of high-grade gliomas. Tumor-related neo-angiogenesis and endothelial cell
      proliferation were also present. The great majority of high-grade astrocytic
      gliomas are incurable with the three classic therapeutic modalities. In the
      future, the development of targeted anti-neoplastic treatment strategies, adapted
      to individual patients, will require molecular identification of the different
      classes of neoplasm (including subtypes of astrocytomas) according to their
      stages, biology, prognosis and therapeutic options.

PMID- 16900783
TI  - Cyclooxygenase-2 (COX-2) overexpression in childhood brain tumors.
AB  - The overexpression of COX enzymes has been demonstrated in human neoplasms at
      various sites, including the colon, gastrointestinal tract, lung, skin and
      recently in brain tumors. In this study, COX-2 receptor overexpression in primary
      childhood brain tumors was determined and the distribution pattern of COX-2
      receptors was examined. A sensitive, 4-step, alkaline phosphatase conjugated
      antigen detection technique was used and a specific monoclonal antibody for
      medulloblastomas/ primitive neuroectodermal tumors (MEDs/PNETs), anaplastic, high
      grade astrocytomas (ASTRs) and in glioblastoma multiformes (GMs) was employed.
      All of the 14 MEDs/PNETs observed demonstrated high levels of immunoreactivity
      (overexpression), with the highest immunostaining intensity (grades A and B).
      However, of the 14 subtypes of astrocytic tumors examined, the COX-2 receptor
      expression level did not even approach those of the MEDs/PNETs levels. However,
      significant differences were found when comparing low grade pilocytic ASTRs to
      high grade anaplastic ASTRs and glioblastomas. In two low grade pilocytic ASTRs,
      the expression level never exceeded 20%, while in high grade glial tumors (6
      anaplastic ASTRs and 6 GMs) 30 to 50% of the tumor cells overexpressed COX-2
      receptors, documenting an increase in COX-2 receptor overexpression with the
      increasing grade of the astrocytic tumor. In view of these findings, it would
      appear likely that COX-2 inhibitors may represent a chemo-preventive tool in
      treating childhood brain tumors, which are the leading cause of solid tumor
      cancer death in children under the age of 20.

PMID- 16900784
TI  - Effects of wogonin on the levels of cytokines and functions of leukocytes
      associated with NF-kappa B expression in Sprague-Dawley rats.
AB  - The objectives of the study were to investigate the effects of wogonin on the
      cytotoxicity, natural killer activity, macrophage phagocytosis, release of
      interleukin-1alpha (IL-1alpha) and tumor necrosis factor-alpha (TNF-alpha), the
      expression of nuclear factor-kappaB (NF-kappaB) in leukocytes from Sprague-Dawley
      rats. Wogonin was added to the medium and the levels of IL-1alpha and TNF-alpha
      in the medium were measured using enzyme-linked immunosorbent assay. Both IL
      1alpha and TNF-alpha mRNAs were measured by reverse transcription polymerase
      chain reaction and the levels of NF-kappaB and I-kappaB were measured by Western
      blotting. Natural killer cell activity and macrophage phagocytosis were measured
      by flow cytometry. The results demonstrated that wogonin induced cytotoxicity in
      rat leukocytes and promoted the activities of natural killer cells and
      macrophages. Wogonin increased the IL-1alpha and TNF-alpha levels in the
      leukocytes in culture media dose-dependently. IL-1alpha and TNF-alpha mRNA
      elevations were also promoted by wogonin. The data suggests that wogonin may
      affect the IL-1alpha and TNF-alpha mRNA expressions by affecting the NF-kappaB in
      rat leukocytes.

PMID- 16900785
TI  - Attenuating effect of artemin on herpes-related pain responses in mice infected
      with herpes simplex.
AB  - The influence of artemin (AR) on herpes-related pain responses was examined using
      mice infected with herpes simplex virus (HSV). BALB/c mice were inoculated with
      HSV (1x10(6) plaque-forming units) on the right hind paw, while the contralateral
      hind paw was without inoculation. The changes in nociceptive threshold were
      examined using an electric Von Fray meter. Intraperitoneal administration of AR
      prevented a decrease in nociceptive threshold dose-dependently in HSV-inoculated
      mice, which was first observed at a dose of 1.0 mg/kg and peaked at doses higher
      than 1.5 mg/kg. This antinociceptive effect of AR attained peaks at 120 min after
      administration and declined gradually to non-treated levels by 270 min.
      Intraperitoneal administration of AR at a dose of 1.5 mg/kg scarcely affected
      beta-endorphin and noradrenaline levels in the central nervous system of HSV
      inoculated mice. However, AR caused a significant decrease of the dynorphin
      levels in spinal cord. These results strongly suggest that AR exerts
      antinociceptive effects on herpes-related pain through changes of the dynorphin
      levels in the central nervous system of HSV-inoculated mice. It is also suggested
      that AR will be a good candidate as an antinociceptive drug for the treatment of
      acute herpetic pain in humans.

PMID- 16900786
TI  - An in vivo model for testing genotoxicity of environmental fibre-associated
      nitroarenes.
AB  - The environmental carcinogens nitroarenes are frequently adsorbed by asbestos
      fibres. An effective dose of 1-nitropyrene was studied in vivo. The mutagenic
      pattern of excreted urine of orally and intraperitoneally exposed rats was tested
      by the Ames mutagenicity assay. The characteristics of detected mutagenicity
      proved to be different in the two routes of exposure. TA 100 mutagenicity was
      only detected following i.p. exposure, while TA 98 revertant frequencies were
      increased significantly only after deconjugation, in both groups. Since
      environmental asbestos exposure involves carcinogenic effects of adsorbed
      polycyclic aromatic hydrocarbons, this animal model provides a useful tool for
      testing fibre-associated nitroarenes, in both mechanistic and risk assessment
      studies.

PMID- 16900787
TI  - Tumor target organs and rate of survival in long-living transgenic mice and their
      parental wild-type counterparts exposed to the carcinogen
      dimethylbenz(a)anthracene.
AB  - Two-year-old mice of the long-living transgenic mice of the alphaMUPA strain were
      previously found to show higher tumor resistance than the their initial wild-type
      (WT) strain (Tirosh, 2003). To better understand the mechanism underlying the
      differences in tumorigenesis rates between the two mouse lines, the rate of
      tumorigenesis and survival effects were studied in alphaMUPA mice and parental WT
      mice exposed to dimethylbenz(a)anthracene (DMBA). Each animal received three
      intragastric feedings of DMBA, each one week apart, at doses of 2, 1, and 1 mg
      dissolved in 0.2 ml corn oil; thus, the total amount of the carcinogen was 4
      mg/mouse. Control mice received corn oil. The alphaMUPA mice exhibited distinctly
      higher survival rates in experimental chemically-induced tumorigenesis compared
      to their WT counterparts: 93% vs. 67%, p =2.7. The rate of tumorigenesis differed
      between the mouse lines (yield was 1.5 and 2.1), owing to a distinct tendency
      toward decreased tumor frequency in the skin and forestomach in the alphaMUPA
      mice. The experimental duration was also significantly higher for transgenic
      mice: 35.9 +/- 1.2 weeks compared to 30.5 +/- 1.3 weeks in WT mice, p <0.01. The
      lungs, forestomach and skin were target organs for the carcinogenic effect of
      DMBA. Our observations suggest that aging promotes the rate of spontaneous and
      induced tumorigenesis.

PMID- 16900788
TI  - Short-term octreotide treatment induces apoptosis in human pancreatic cancer
      xenografts.
AB  - BACKGROUND: It was previously demonstrated that octreotide (Sandostatin) induced
      an increased apoptotic activity in human pancreatic cancer xenografts after a
      high dose, 1-month treatment. In the present study the effect of smaller doses
      (2x100 microg/kg b.w.) administered in a short-term (4-day) experiment were
      investigated. MATERIALS AND METHODS: CBA immunosuppressed mice bearing human
      pancreatic carcinoma (PXZ-40/6) were treated daily with 2x100 microg/kg b.w.
      Sandostatin subcutaneously for 4 consecutive days. The number of tumor cells
      displaying apoptotic bodies (late event) and mitotic activity were assessed by
      morphometry, while the earlier phase of the apoptotic process was determined
      using flow cytometry. RESULTS: A short octreotide treatment did not influence the
      mitotic activity, but the number of apoptotic cells decreased significantly (1.8
      +/- 0.44/mm2 in controls vs. 6.8 +/- 1.0/mm2 in treated tumors, p < 0.0009). The
      percentage of nuclei in sub-G1 phase almost doubled (6.0 +/- 0.75% in-controls,
      11.2 +/- 0.97% in the octreotide-treated group, p<0.0014). The DNA index and the
      proliferation indices proved to be unchanged. CONCLUSION: The results suggest
      that low doses of octreotide induce apoptosis in human pancreatic cancer
      xenografts after a short-term treatment.

PMID- 16900789
TI  - Pegylated Liposomal Doxorubicin HCL (Caelyx) in combination with Sandostatin LAR
      as salvage therapy in patients with small-cell lung cancer.
AB  - BACKGROUND: The aim of the present study was to evaluate the efficacy of
      Pegylated Liposomal Doxorubicin (Caelyx) combined with Sandostatin LAR as salvage
      treatment of small cell lung cancer (SCLC) in platinum-pretreated patients.
      PATIENTS AND METHODS: Nine pretreated patients (median age 53.5 years, PS: 0-1)
      with histologically confirmed SCLC were treated with Caelyx 40 mg/m2 (i.v.) on
      day 1 and Sandostatin LAR 30 mg (i.m.) on day 1 every 28 days. Four (44%) out of
      the nine patients had received two prior regimens and five (55%) were refractory
      to front-line chemotherapy. RESULTS: No complete or partial responses were
      observed. Disease stabilization was obtained in two (22%) patients. The median
      overall survival was 18.7 months and the median time to progression was 9.1
      months. CONCLUSION: The combination of Caelyx and Sandostatin LAR was inactive as
      salvage treatment in this poor prognosis group of patients with relapsed SCLC.
      However, the combination would merit further investigation in patients pretreated
      with one prior regimen.

PMID- 16900790
TI  - Vincristine-laden platelet transfusion for patients with refractory
      thrombocytopenia.
AB  - BACKGROUND: The aim of the present study was to assess the efficacy of
      vincristine-laden platelet transfusion for patients with refractory
      thrombocytopenia. PATIENTS AND METHODS: Twenty evaluable patients who received
      vincristine-laden platelets for refractory thrombocytopenia were included in this
      retrospective study. Vincristine (1 mg) was added to the platelets and incubated
      for one hour prior to transfusion. Serial platelet counts following vincristine
      laden platelet transfusion and units of platelets transfused in the week prior to
      and the week after transfusion of vincristine-laden platelets were evaluated.
      RESULTS: The underlying diseases of the patients were lung cancer (n =4), breast
      cancer following autologous hematopoietic stem cell transplantation and acute
      myeloid leukemia (n=3 each), myelodysplastic syndrome (n=2), acute lymphoid
      leukemia, chronic lymphoid leukemia, chronic myeloid leukemia, multiple myeloma,
      ovarian cancer, aspergillosis, cytomegalovirus infection and systemic lupus
      erythematosus (n = 1 each). The median rate of change of platelet count after
      transfusion of vincristine-laden platelets was 550/microL/day (range, -1,000 to
      12,8001/microL/day; p=0.003). The median change in the number of units of
      platelets transfused in the week following vincristine-laden platelet transfusion
      was -1.5 as compared to the week prior to the transfusion (p=0.031). Patients
      with a primary marrow disorder exhibited no difference in either the rate of
      change in platelet count or in the difference in the units of platelets
      transfused compared to those without a primary bone marrow disorder. CONCLUSION:
      Vincristine-laden platelet transfusion was associated with significantly
      increased platelet counts and a subsequent decrease in platelet transfusion.

PMID- 16900791
TI  - Leptin alterations in the course of sepsis in humans.
AB  - Neuroendocrine response to sepsis may be divided into acute and prolonged phase.
      As leptin is implicated in the stress response, leptin's profile during both
      phases, and the possible relationships between leptin and the neuroendocrine
      response to sepsis were investigated. Thirty adult patients with sepsis in an
      intensive care unit were studied. Blood samples were collected at the acute and
      the prolonged phases. In acute sepsis, leptin levels were higher in patients than
      in controls (10.2 +/- 2.5 vs. 4.1 +/- 1.2 ng/ml, p =0.01) and correlated
      positively with insulin levels and insulin resistance. A decline in leptin levels
      was found during prolonged sepsis (from 10.2 +/- 2.5 to 6.2 +/- 1.7 ng/ml,
      p=0.001), which was not related to survival (p=0.913). At the onset of sepsis,
      leptin levels increased in correlation with insulin and insulin resistance,
      possibly indicating a cause-effect relationship. However, the decline in leptin
      levels during the prolonged phase of sepsis was not related either to survival or
      to metabolic and hormonal changes.

PMID- 16900792
TI  - The Moroccan health care system.
AB  - In comparison with the 1950s, although deficient in many aspects, Morocco's
      health care system has made major progress. It aspires to improve in performance
      through reforms, implementation of well-conceived and strategic plans and the
      adoption of the Health Insurance Card scheme, which is still under review by the
      government.

PMID- 16900793
TI  - Physician accountability, patient safety and patient compensation.
AB  - In Canada, the response to adverse medical events follows one or more of three
      main paths: patient safety, physician accountability and patient compensation.
      While their goals differ, each of these responses serves a valuable function.
      There are however competing imperatives inherent in each response, particularly
      in terms of information disclosure: Effective patient safety depends on the full
      and protected disclosure of all information relevant to an adverse event and
      requires a "no blame" environment. While natural justice demands that a physician
      be held accountable for his actions, the doctor should be accorded the right of
      due process and be judged against an established standard of care. This is
      necessarily a fault-finding activity. Patient compensation meets both
      accountability demands and the social justice imperatives of supporting a patient
      injured through physician negligence. The most effective approach is one that
      achieves balance between competing imperatives. With clear information disclosure
      rules, patient safety, physician accountability and patient compensation can
      operate synergistically.

PMID- 16900794
TI  - The role of risk management in reducing costs and increasing patient safety.
AB  - In the last few years risk managers have been very frustrated with the high
      costs, or sheer unavailability, of medical malpractice insurance. The frustration
      is very understandable, given the rising financial costs of litigation for
      medical negligence. This presentation will aim to recommend a way out of this
      conundrum which works equally well regardless of whether the prevailing
      litigation environment be high or low, or one which is a fault-based or no-fault
      based compensation system, or whether a conventional insurance, self-insurance,
      or pooled risk insurance scheme. This paper will seek further to recommend that
      it's time risk managers took more responsibility themselves for reducing medical
      errors and optimising their control of risk. By understanding the concept of
      Total Cost of Risk, risk managers would be able to reduce losses, relying less on
      the insurance market, and accept responsibility for risk themselves, and, as a
      result, lowering insurance premiums in the process as the risk will have been
      taken away from insurance underwriters.

PMID- 16900795
TI  - Using SERVQUAL and Kano research techniques in a patient service quality survey.
AB  - This article presents the results of a service quality study. After an
      introduction to the SERVQUAL and the Kano research techniques, a Kano analysis of
      75 patients from the General Hospital of Katerini in Greece is presented. The
      service quality criterion used satisfaction and dissatisfaction indices. The Kano
      statistical analysis process results strengthened the hypothesis of previous
      research regarding the importance of personal knowledge, the courtesy of the
      hospital employees and their ability to convey trust and confidence (assurance
      dimension). Managerial suggestions are made regarding the best way of acting and
      approaching hospital patients based on the basic SERVQUAL model.

PMID- 16900797
TI  - Genodermatoses care in the Mediterranean region: a new initiative.
AB  - This article looks at a regional initiative to improve the quality of medical and
      social care for patients with severe skin diseases. The programme called
      "Genodermatoses and the Mediterranean--Together for a better care" aims to use
      shared international experience to alleviate the painful aspects of this
      condition and the methods used to facilitate this.

PMID- 16900798
TI  - Health care IT adoption could save USD162 billion.
AB  - This article looks at how health care IT can save hospitals and health services
      valuable funding and how these saving compare to the costs involved. The chief
      barriers to success and possible solutions to these difficulties are outlined.
      The author also points to the need for government intervention in implementing
      health care IT on a board scale.

PMID- 16900799
TI  - What role should leadership, rather than management, play in improving health
      services?

PMID- 16900800
TI  - Fertility, contraception, and fatherhood: data on men and women from cycle 6
      (2002) of the 2002 National Survey of Family Growth.
AB  - OBJECTIVE: This report presents national estimates of fertility, family
      formation, contraceptive use, and father involvement indicators among males 15-44
      years of age in the United States in 2002 from Cycle 6 of the National Survey of
      Family Growth (NSFG). Data are also shown for women for purposes of comparison.
      METHODS: Descriptive tables of numbers and percentages are presented. Data were
      collected through in-person interviews of the household population 15-44 years of
      age in the United States between March 2002 and March 2003. The sample included
      7,643 females and 4,928 males. This report focuses primarily on data from the
      male sample, but compares findings with the female data whenever appropriate. The
      overall response rate for Cycle 6 of the NSFG was 79 percent, and the response
      rate for men was 78 percent. RESULTS: This report covers a wide range of topics
      including first sexual intercourse and its timing in relation to marriage;
      contraceptive use; wantedness of births in the past 5 years; marital and
      cohabiting status at first birth; living arrangement of fathers with their
      children; father's activities with children they live with and those they do not
      live with; HIV-risk related behaviors; and infertility services. CONCLUSION: The
      reproductive experiences of men and women 15-44 years of age in the United States
      vary significantly, and often sharply, by demographic characteristics such as
      education, income, and Hispanic origin and race.

PMID- 16900801
TI  - Fibrin sealant reduces pain after tonsillectomy: prospective randomized study.
AB  - OBJECTIVES: Postsurgical pain in adults following tonsillectomy with fibrin
      sealant or electrocoagulation was assessed by surface electromyography (sEMG), a
      dysphagia severity rating scale (DSRS), and a visual analog scale (VAS) pain
      METHODS: For group 1 (n = 40), hemostasis was achieved by fibrin sealant spraying
      to the tonsillar fossae. For group 2 (n = 40), hemostasis was achieved by bipolar
      or needle point electrocautery. The timing of single swallowing and continuous
      drinking and the mean electrical activity of the masseter, infrahyoid, and
      submental-submandibular muscles were compared with a normative database during 30
      days and with DSRS and VAS scores. RESULTS: Electrical activity of the masseter
      and infrahyoid muscles was significantly higher in both groups in comparison with
      the normative database (p < .05 to p < .005), whereas timing was less affected.
      The combined sEMG, DSRS, and VAS assessment showed that tonsillectomy ended with
      sealant causes less pain than electrocoagulation (p < .05). The DSRS score data
      were in strong positive correlation with the sEMG records, whereas the VAS pain
      score was less informative. CONCLUSIONS: The combined sEMG and pain score data
      indicate that the electrocautery hemostatic technique is more painful and
      traumatic than the sealant technique. Surface electromyography of swallowing is a
      simple, reliable evaluation method for postsurgical odynophagia complaints and
      might be used as an objective tool for pain assessment.

PMID- 16900802
TI  - Preoperative corticosteroid oral therapy and intraoperative bleeding during
      functional endoscopic sinus surgery in patients with severe nasal polyposis: a
      preliminary investigation.
AB  - OBJECTIVES: The aim of the study was to investigate whether orally administered
      steroids might improve surgical field conditions during functional endoscopic
      sinus surgery. METHODS: Total blood loss and visualization of the surgical field
      during the surgical procedure were compared in 2 groups of 18 patients each with
      severe nasal polyposis. The groups were similar in respect to age, body mass
      index, general health status, incidence of allergy, bronchial asthma, aspirin
      triad, and stage of disease. One group received 30 mg of prednisone daily for 5
      consecutive days before the operation. The second group served as a control.
      RESULTS: Although the total blood loss was only slightly less in the steroid
      group, the visual conditions of the surgical field improved significantly.
      CONCLUSIONS: Better surgical field conditions were the results of the powerful
      anti-inflammatory and antiedematous activity of the drug, which facilitated blood
      and secretion evacuation from the operated area and prevented the optic system
      from staining.

PMID- 16900803
TI  - Spontaneous cerebrospinal fluid leaks: a variant of benign intracranial
      hypertension.
AB  - OBJECTIVES: Previous reports indicate that elevated intracranial pressure (ICP)
      may cause spontaneous cerebrospinal fluid (CSF) leaks. In this study we examined
      the clinical diagnosis of benign intracranial hypertension (BIH) in this
      population using the modified Dandy criteria. METHODS: We performed a
      retrospective review of clinical data and measurements of ICPs after surgical
      repair. RESULTS: Sixteen patients with spontaneous CSF leaks were surgically
      treated from 1996 to 2002. In 11 patients with CSF pressure measurements, strict
      adherence to the modified Dandy criteria definitively confirmed a diagnosis of
      BIH in 8 patients (72%) and a likely diagnosis in the 3 remaining patients. The
      mean ICP was 31.1 cm H20 (range, 17.3 to 52 cm H2O), and 81% of the patients were
      obese middle-aged women. Clinically, all patients had signs and/or symptoms of
      elevated ICP, such as headache (91%), pulsatile tinnitus (45%), hypertension
      (45%), balance problems (27%), and visual complaints (18%). Surgical repair was
      100% successful in leak cessation over a mean follow-up of 14.1 months.
      CONCLUSIONS: Most patients with spontaneous CSF leaks fulfill the modified Dandy
      criteria; thus, this disorder appears to be a variant of BIH. Further
      investigation is needed to determine the exact cause of elevated CSF pressures in
      this group and whether medical or surgical treatments to correct the intracranial
      hypertension are warranted.

PMID- 16900804
TI  - Tissue engineering for regeneration of the tracheal epithelium.
AB  - OBJECTIVES: The slowness of epithelialization on the artificial trachea that has
      been successfully used in humans is a problem. The purpose of this study was to
      develop a way to regenerate the epithelium on the surface of this artificial
      trachea. METHODS: In an in vitro study, isolated rat tracheal epithelial cells
      were seeded on a collagenous gel that was stratified on a collagenous sponge.
      Histologic and immunohistochemical examinations were made. In an in vivo study,
      we transplanted grafts with green fluorescent protein-positive tracheal
      epithelial cells onto the tracheal defects of normal rats. At 3, 7, 14, and 30
      days after the operation, histologic and immunohistochemical examinations were
      made. RESULTS: In the in vitro study, the 3 layers--the epithelium, gel, and
      sponge--could be observed. The epithelium expressed cytokeratin 14, cytokeratin
      18, and occludin. In the in vivo study, the artificial trachea was covered with
      epithelium at 3 days after operation, and then the epithelium differentiated from
      single- or double-stratified squamous epithelium into columnar ciliated
      epithelium. Green fluorescent protein-positive cells were found 3 days after
      operation. CONCLUSIONS: We believe that the method used in our experiment is an
      effective way to regenerate the epithelium on the surface of an artificial
      trachea. With further experimentation, this method should be suitable for
      clinical application.

PMID- 16900805
TI  - Airway manifestations of pediatric eosinophilic esophagitis: a clinical and
      histopathologic report of an emerging association.
AB  - OBJECTIVES: Pediatric eosinophilic esophagitis (EE) typically presents with
      dysphagia, vomiting, dyspepsia, or food impaction. The purpose of this study was
      to highlight the emerging association of pediatric EE and airway disease. An
      additional goal of this study was to describe the unique histopathologic findings
      found in EE and specifically explore the potential role of the cytotoxic protein
      called eosinophil major basic protein (MBP) in the pathophysiology of the
      disease. METHODS: A retrospective review of 3 children with EE and airway
      symptoms included symptom presentation, aerodigestive tract endoscopic findings,
      ambulatory 24-hour dual pH-metry, allergy tests, treatment modalities, and
      treatment response. Esophageal tissue obtained from biopsies of each patient was
      evaluated by hematoxylin and eosin to determine the number of eosinophils per
      high-power field, by immunofluorescent anti-MBP staining to determine the
      presence of MBP, and by standard light and transmission electron microscopy to
      evaluate eosinophil migration patterns. RESULTS: All patients had airway
      inflammation that included nonspecific laryngeal edema and grade I or II
      subglottic stenosis. Allergy testing was positive in the 2 patients who were
      tested. All patients had symptoms refractory to standard reflux therapy.
      Ambulatory pH-metry findings were normal in 2 patients and abnormal in 1 patient
      despite maximum treatment. Two patients had visual abnormalities seen during
      esophageal examination. The number of eosinophils ranged from 20 to 45 per high
      power field. Intracellular and extracellular MBP deposition was found in all
      esophageal biopsy specimens. All patients were treated with swallowed
      fluticasone, and 2 had symptom relapses that required repeat treatment.
      CONCLUSIONS: The spectrum of pediatric EE can include upper airway disease.
      Intracellular and extracellular MBP deposition is present in EE, which
      potentially releases cytotoxic mediators that explain the esophageal and airway
      clinical symptoms seen in those with the disease. Eosinophilic esophagitis should
      be considered in patients with a history of atopic diseases and unexplained upper
      airway findings refractory to reflux treatment. Treatment with swallowed
      fluticasone is successful; however, relapses are common and require repeat
      treatment and close follow-up.

PMID- 16900806
TI  - Temperature-dependent auditory neuropathy: is it an acoustic Uhthoff-like
      phenomenon? A case report.
AB  - OBJECTIVES: We describe the case of a young girl in whom transient deafness
      occurred when her core body temperature rose. METHODS: The patient was referred
      for a series of audiological and neurologic evaluations performed over time in
      both afebrile and febrile states, as well as after a stress test (with a
      treadmill) in which the body temperature rise simulated the febrile state.
      RESULTS: The patient was found to have a temporary bilateral hearing loss, but
      had normal distortion product otoacoustic emissions. Moreover, auditory brain
      stem responses revealed the absence of neural synchrony when her core body
      temperature increased. CONCLUSIONS: These results are consistent with a
      temperature-dependent auditory neuropathy, a rare condition in which patients
      show normal outer hair cell function and abnormal neural function of the eighth
      cranial nerve. The symptom is reminiscent of Uhthoff's phenomenon, which is
      described as transient visual loss and is usually observed in multiple sclerosis.
      This case of temperature-dependent auditory neuropathy is noteworthy because it
      sheds light on a disorder of which there have been few reports in the literature.
      We discuss its similarity to Uhthoff's phenomenon.

PMID- 16900807
TI  - Sensory testing in the assessment of laryngeal sensation in patients with
      amyotrophic lateral sclerosis.
AB  - OBJECTIVES: Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron
      disease of unknown cause. Mortality in the population is frequently due to
      aspiration pneumonia. Although typically considered to be a disorder limited to
      motor neuron involvement, some investigators have indicated that decreased
      sensory function in ALS patients additionally contributes to the disease process.
      The objective of this study was to evaluate laryngopharyngeal sensation in the
      ALS population in order to quantify the range of sensory deficits and correlate
      any abnormalities with demographic data to determine which patients are at risk
      of having sensory deficits. METHODS: We examined the sensation of the larynx in
      22 patients with ALS to determine whether a sensory deficit was present. After
      completion of a dysphagia questionnaire and medical history, patients underwent
      flexible endoscopic evaluation of swallowing with sensory testing (FEESST) to
      evaluate sensory function. Threshold values were determined and recorded for
      initiation of the adductor reflex. RESULTS: The results of the sensory and
      swallowing function assessments performed on 22 patients demonstrate abnormal
      sensation in 54.5% of the tested population. Asymmetric findings were noted in
      75% of these patients. There was no correlation noted between the presence of
      sensory deficits and the severity or duration of the disease. CONCLUSIONS:
      Progressive dysphagia in the ALS population has typically been attributed to
      muscle weakness. This study points to the presence of sensory deficits in the
      larynx, which can further affect proper swallowing function.

PMID- 16900808
TI  - Carbon dioxide laser fiber for laryngeal cancer surgery.
AB  - OBJECTIVES: The carbon dioxide laser has evolved to be the premier dissecting
      instrument for hemostatic cutting during endolaryngeal cancer resection. However,
      dissection is limited to mirror-reflected line-of-sight delivery of the laser. A
      recently developed flexible, hollow photonic bandgap fiber (PBF) appears to offer
      advantages in endolaryngeal dissection. METHODS: The suitability of the PBF for
      human application was evaluated in a canine experiment in which human surgical
      procedures for microlaryngoscopic en bloc partial laryngectomy were simulated.
      The specimens that were resected endoscopically and the completion laryngectomy
      specimen were evaluated histologically. RESULTS: Observations from this
      experiment revealed that en bloc partial laryngectomy procedures were
      substantially easier to achieve as compared with prior experience in humans. This
      improvement resulted from three factors: 1) enhanced tangential dissection due to
      increased angulation of the laser energy, 2) enhanced procedural orientation due
      to proprioception of the tissues in contact mode, and 3) improved hemostasis.
      Histopathologic analysis of the resection margins revealed minimal thermal
      trauma. CONCLUSIONS: The PBF shows substantial promise for human application in
      endoscopic partial laryngectomy. It will likely enhance the ability of any
      surgeon to extend his or her indications for performing endoscopic laryngeal
      cancer resections regardless of philosophy (en bloc resection or piecemeal).

PMID- 16900809
TI  - Classroom performance of children with cochlear implants in mainstream education.
AB  - OBJECTIVES: We compared classroom performance of children with a cochlear implant
      (CI) with that of their normal-hearing peers in mainstream education. METHODS:
      Thirty-two CI children in mainstream education, congenitally or prelingually
      deaf, participated in this study, as did 37 hearing classmates. Their teachers
      filled out 2 questionnaires: the Assessment of Mainstream Performance (AMP) and
      the Screening Instrument for Targeting Educational Risk (SIFTER). A high Fletcher
      index and open-set speech perception scores were obtained. RESULTS: The children
      with CIs scored above average on the AMP and sufficiently well in all but one
      area (communication) of the SIFTER questionnaire. Class rankings did not differ
      significantly between the CI students and their normal-hearing peers. Overall,
      the normal-hearing group outperformed the CI group. The classroom performance of
      CI children correlated negatively with duration of deafness and age at
      implantation. All longitudinal audiological data of the CI children showed
      improvement in open-set speech recognition. CONCLUSIONS: Although the results are
      encouraging, the CI group scored significantly less well than their normal
      hearing peers on most questionnaire domains of both the AMP and the SIFTER. The
      most important variables for the outcome in this study were age at implantation
      and duration of deafness.

PMID- 16900810
TI  - Prognostic factors in sudden sensorineural hearing loss: our experience and a
      review of the literature.
AB  - OBJECTIVES: We investigated prognostic factors in sudden sensorineural hearing
      loss (SSNHL). METHODS: Our study group consisted of 133 patients with SSNHL who
      were treated at our department between 1980 and 2000. Eighty-one of them (group
      B) were treated between 1980 and 1996; they received vasodilators and small doses
      of steroids. The others (52 patients; group A) were treated between 1997 and
      2000; they received vasodilators, steroids at high doses, and hyperbaric oxygen.
      A multivariate stepwise linear regression was used to identify the prognostic
      factors that were related to hearing improvement as measured by objective change
      of gain in the overall average (0.5, 1, 2, 4, 6, 8 kHz), the pure tone average
      (0.5, 1, 2 kHz), the high tone average (4, 6, 8 kHz), and the pure middle tone
      average (0.5, 1, 2, 4 kHz). The following factors were included in the analysis:
      group (method of treatment), age, gender, seasonal occurrence of disease,
      presence of tinnitus and vestibular symptoms, time delay before first visit, type
      of initial audiogram, and type of caloric reaction. In group A, an additional
      analysis was conducted to include the results of certain laboratory tests: blood
      morphology parameters, erythrocyte sedimentation rate, glucose level,
      coagulogram, lipidogram, thyroid-stimulating hormone, autoantibodies
      (antimitochondrial antibodies, smooth muscle antibodies, and anti-brush border
      antibodies), and immunoglobulins G, A, and M. Values for p of less than .05 were
      considered significant. RESULTS: Our analysis suggests the presence of the
      following prognostic factors for SSNHL: method of SSNHL treatment (better results
      in group A); time delay before the start of treatment (better results when
      treatment started within 10 days of the first symptoms of SSNHL); and type of
      caloric reactions (worse results in patients with canal paresis). In group A, the
      factors for poor prognosis for absolute hearing improvement were as follows:
      delayed treatment, labyrinth responsiveness disorders, and decreased level of
      thyroid-stimulating hormone. In group A, better hearing improvement was observed
      in those patients in whom SSNHL was diagnosed in the spring. CONCLUSIONS: A short
      time delay before starting treatment (within 10 days), treatment with high doses
      of steroids and hyperbaric oxygen, preserving complete caloric function of the
      labyrinths, normal function of the thyroid, and seasonal occurrence of the
      disease in the spring were positive prognostic factors for hearing recovery in
      SSNHL.

PMID- 16900811
TI  - Imaging case study of the month. Thyroglossal duct cyst with intralaryngeal
      extension.
AB  - OBJECTIVES: Thyroglossal duct cysts with intralaryngeal extension are rare. We
      present only the 10th reported case in the literature. METHODS: The clinical
      presentation, diagnosis, and treatment of the patient are reviewed and
      summarized. The uniqueness of the case, as well as the diagnostic and treatment
      pitfalls of this subgroup of patients, is presented. RESULTS: Our patient, at 76
      years of age, is the only woman and the oldest person reported to have had a
      thyroglossal duct cyst with intralaryngeal extension. CONCLUSIONS: Intralaryngeal
      extension should be considered when there is hoarseness, dysphagia, or dyspnea
      associated with a thyroglossal duct cyst. Office laryngoscopy and computed
      tomography make the diagnosis. Care must be taken with airway management and
      intraoperative dissection for good outcomes.

PMID- 16900813
TI  - Commentary on the role of basic and translational research.

PMID- 16900812
TI  - Which surface properties enhance bone response to implants? Comparison of
      oxidized magnesium, TiUnite, and Osseotite implant surfaces.
AB  - PURPOSE: This study compared the speed and strength of osseointegration and
      osteoconductivity between an oxidized experimental magnesium (Mg) implant, an
      oxidized commercially available TiUnite implant, and a dual acid-etched surface
      Osseotite implant. The aim was to investigate which surface properties enhance
      bone response to implants, and thereby to test a biochemical bonding theory.
      MATERIALS AND METHODS: A total of 60 screw implants (20 of each design) were
      inserted through 1 cortex into the tibiae of 10 rabbits. Surface chemistry, oxide
      thickness, morphology, crystal structure, and surface roughness were evaluated.
      After healing times of 3 and 6 weeks, all bone implants were unscrewed with
      removal torque (RTQ) devices, and the bone specimens were subjected to
      histomorphometry. RESULTS: RTQ values for Mg, TiUnite, and Osseotite implants
      were 27.1, 21.3, and 15.4 Ncm, with new bone formation values of 29%, 18%, and
      15%, respectively, at 3 weeks. At 6 weeks the RTQ values were 37.5, 36.4, and
      21.5 Ncm, with new bone formation values of 39%, 31%, and 26%, respectively.
      DISCUSSION: Mg implants demonstrated significantly greater RTQ values (P = .008
      and P = .0001) and more new bone formation (P = .031 and P = .030) than Osseotite
      at 3 and 6 weeks, respectively. Mg implants also showed higher RTQ values at 3
      weeks and new bone formation at 6 weeks than TiUnite, but neither were
      significant (P > .05). TiUnite showed significantly higher RTQ values than
      Osseotite at 6 weeks (P = .001), but was not significant at 3 weeks (P > .05).
      Osseointegration rate (deltaRTQ/deltaweeks) was significantly faster for Mg (P =
      .011) and TiUnite (P = .001) implants between 3 and 6 weeks of healing time, but
      was not significant for Osseotite. CONCLUSIONS: The results indicate that surface
      chemistry facilitated more rapid and stronger osseointegration of the Mg implants
      despite their minimal roughness compared to the moderately roughened TiUnite.
      This suggests potential advantages of Mg implants for reducing high implant
      failure rates in the early postimplantation stage and in compromised bone, making
      it possible to shorten bone healing time from surgery to functional loading, and
      enhancing the possibility of immediate/early loading.

PMID- 16900814
TI  - In vitro wear of different material combinations of intracoronal precision
      attachments.
AB  - PURPOSE: This study examined the retentive forces of intracoronal precision
      attachments after wear cycling. MATERIALS AND METHODS: Three material
      combinations of an intracoronal cylindric T-attachment were tested. A total of
      10,000 separating and joining movements were performed, and retentive forces were
      measured. RESULTS: Components made of gold alloy performed significantly better
      (P = .002) than other materials. The average proportional loss of retention was
      90% for titanium and 47% for gold alloy components. CONCLUSION: Cyclic loading of
      metal precision attachment components results in loss of retention, which can be
      fully compensated by reactivating internal screws in the patrices. Machined, high
      noble gold alloys show less wear than other materials.

PMID- 16900815
TI  - Prediction of TMJ arthralgia according to clinical diagnosis and MRI findings.
AB  - PURPOSE: The aim of this study was to investigate the ability of clinical and
      magnetic resonance imaging (MRI) diagnoses to predict pain in the
      temporomandibular joint (TMJ). MATERIALS AND METHODS: One hundred forty-nine
      patients were examined by 2 calibrated examiners in strict accordance with the
      Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD). All
      patients who presented with a defined clinical RDC/TMD diagnosis were included
      and underwent bilateral coronal and sagittal MRI of the TMJ. Two raters blinded
      to the clinical diagnosis interpreted the MRI scans for TMJ pathology. The
      results were tested against the clinical diagnosis according to the RDC/TMD,
      including pain-related disability and psychosocial status, for associations to
      TMJ arthralgia using logistic regression analysis (GENMOD procedure, P < .05).
      RESULTS: MRI-depicted anatomic changes, such as joint effusions, disc
      displacement, and osteoarthrosis, were not significantly correlated with the
      presence of pain in the TMJ. However, a significant relationship between pain on
      palpation of the masseter muscle origin (P = .0050) and psychosocial factors (P =
      .0452) and pain in the TMJ was demonstrated. CONCLUSIONS: Pain in the TMJ caused
      by the anatomic proximity of the muscle masseter origin and the lateral TMJ pole
      and the possible existence of trigger points in the musculature may lead to a
      false-positive or a false-negative diagnosis of arthralgia. Additionally,
      clinicians must consider the psychosocial aspects of pain in ideal treatment
      planning.

PMID- 16900816
TI  - Influence of implant and conventional prostheses on satisfaction and quality of
      life: A literature review. Part 2: Qualitative analysis and evaluation of the
      studies.
AB  - PURPOSE: To review the influence of prosthodontic and dental implant treatment on
      patient satisfaction and oral health-related quality of life (OHQOL) based on a
      systematic search of the literature. MATERIALS AND METHODS: A systematic
      literature search was carried out for articles published between 1960 and
      February 2003. Details of the search process and results were reported in Part 1
      of the study (Int J Prosthodont2004;17:83-93). The included studies were
      categorized and evaluated according to their level of evidence, following the
      guidelines of the Agency for Health Care Policy and Research. The characteristics
      and content of the studies were analyzed and tabulated. RESULTS: Among the 114
      included studies, there were 76 publications reaching evidence level III. The
      results showed that the effects of compromised oral health are not limited to
      traditional clinical aspects, but can considerably affect patients in various
      activities of daily life. Twenty-four of the 38 investigations with evidence
      levels I and II dealt with implant stabilization of complete mandibular
      prostheses, comparing implant prostheses to conventional complete dentures. Fully
      edentulous patients experience negative impacts on OHQOL from their condition.
      They benefit significantly from the use of dental implants to support mandibular
      prostheses. However, support by more than 2 implants does not appear to further
      significantly increase patient satisfaction and OHQOL. CONCLUSIONS: To date,
      research in the field of patient-based outcomes has concentrated on dental
      implant treatment for the edentulous patient. Other prosthetic treatments such as
      single crowns, fixed and removable partial dentures, or further treatment
      concepts (eg, the shortened dental arch concept) are not well represented. The
      use of patient-centered outcome measures can help to find an individual, patient
      oriented prosthetic solution.

PMID- 16900817
TI  - A randomized clinical trial of cusp-replacing resin composite restorations:
      efficiency and short-term effectiveness.
AB  - PURPOSE: This study aimed to assess the efficacy and short-term effectiveness of
      the morphology and function of direct and indirect cusp-replacing resin composite
      restorations. MATERIALS AND METHODS: In 94 patients, 106 cusp-replacing
      restorations for maxillary premolars were fabricated to restore Class II caries
      lesions with 1 cusp missing. Fifty-four direct (Clearfil AP-X) and 52 indirect
      (Estenia) resin composite restorations were placed following a strict protocol.
      The treatment technique and operator were assigned randomly. Treatment time was
      recorded for all restorations. One-month postoperative evaluation included
      assessment of postoperative sensitivity and presence of occlusal and proximal
      contacts. RESULTS: Treatment time for the indirect technique (68 +/- 17 min) was
      longer than for the direct technique (45 +/- 13 min). Regression analysis
      revealed that the restorative method, operator, and location of the preparation
      outline had a statistically significant effect on the total treatment time.
      Occlusal contacts were observed in 94% of the direct restorations and in 98% of
      the indirect restorations (chi-square, P>.05). Mesial proximal contacts were
      present in 98% of the direct and in 97% of the indirect restorations (chi-square,
      P > .05). Distal contacts were present in 100% of the restorations for both
      techniques. Postoperative sensitivity within 1 week posttreatment was reported
      for 11% of the direct restorations and for 13% of the indirect restorations, but
      decreased to 4% and 6%, respectively, after 1 month (chi-square, P > .05).
      CONCLUSION: The results of this study suggest that in the short term, both direct
      and indirect adhesive techniques are adequate to restore the morphology and
      function of premolars presenting with Class II caries lesions and a missing cusp.

PMID- 16900818
TI  - Clinical long-term results of VITA In-Ceram Classic crowns and fixed partial
      dentures: A systematic literature review.
AB  - PURPOSE: VITA In-Ceram Classic is a system designed to fabricate all-ceramic
      crowns and fixed partial dentures (FPDs) with a glass-infiltrated aluminum oxide
      core material. This systematic literature review gives an overview of the
      clinical performance of the VITA In-Ceram Classic Alumina, Spinell, and Zirconia
      restorations. MATERIALS AND METHODS: Based on a systematic literature review, an
      evidence-based selection and assessment of clinical studies of VITA In-Ceram
      Classic ceramics was carried out. RESULTS: A total of 299 publications were
      found, 21 of which met the inclusion criteria. Only a few meaningful studies of
      In-Ceram Alumina FPDs and In-Ceram Zirconia crowns and FPDs were found. The 5
      year survival rate of In-Ceram Alumina crowns and In-Ceram Spinell crowns ranged
      from 91.7% to 100% and is similar to the survival rate of conventional metal
      ceramic crowns. The 5-year survival rate of single-retainer In-Ceram Alumina
      resin-bonded FPDs (RBFPDs) was 92.3%, which is higher than that of 2-retainer
      RBFPDs. CONCLUSION: In-Ceram Classic Alumina can be recommended for anterior and
      posterior crowns as well as for anterior single-retainer RBFPDs. Further studies
      should be initiated to evaluate in detail the clinical performance of In-Ceram
      Classic Alumina FPDs. In-Ceram Classic Spinell can be recommended for anterior
      crowns, especially if highly esthetic results are requested. For In-Ceram Classic
      Zirconia crowns or FPDs no statement can be made presently because of
      insufficient data.

PMID- 16900819
TI  - The effect of personality type on denture satisfaction.
AB  - PURPOSE: The aim of this study was to determine the correlation between
      personality type and denture satisfaction of totally and partially edentulous
      patients. MATERIALS AND METHODS: Two hundred thirty-nine patients (107 women and
      132 men) aged 31 to 78 years (mean, 51.87) using removable dentures (165
      maxillary and mandibular partial, 51 maxillary and mandibular complete, and 23
      maxillary complete and mandibular partial) were asked to fill out a questionnaire
      on their satisfaction with their dentures with regard to esthetics, speaking
      ability, and masticatory function. Personality types were evaluated using both
      the responses to this questionnaire and the Type A Behavior Pattern Test. Chi
      square test and logistic regression analysis were used to compare the denture
      satisfaction scores of the groups (Type A, Type B, and Type AB). The level of
      statistical significance was set at P = .05. RESULTS: Denture satisfaction of the
      patients with regard to esthetics, speaking ability, and masticatory function was
      affected by personality type. Statistically significant differences were found
      between Type A and types B and AB, as well as between types B and AB. CONCLUSION:
      The personality type of the patients had an effect on their satisfaction with
      dentures. The lowest denture satisfaction values were observed in the Type A
      patients.

PMID- 16900820
TI  - Comparison of the retentive characteristics of cobalt-chromium and commercially
      pure titanium clasps using a novel method.
AB  - This study aimed to compare the retentive forces of cast cobalt-chromium (Co-Cr)
      and commercially pure titanium (cpTi) clasps. A clasp assembly comprising a pair
      of symmetrical clasps was made to fit the opposite halves of a hardened stainless
      steel sphere. This twin clasp was designed to counterbalance the tipping forces
      when the clasp assembly was drawn from the sphere. A total of 120 clasp
      assemblies were fabricated in cast Co-Cr and cpTi and placed at undercut depths
      of 0.25 mm, 0.50 mm, and 0.75 mm (n = 20 for each). For Co-Cr clasps, the
      retentive forces at these undercuts depths were 2.34 +/- 0.23 N, 4.65 +/- 0.35 N,
      and 7.56 +/- 0.50 N, respectively. The corresponding retentive forces for cpTi
      clasps were 1.24 +/- 0.13 N, 2.34 +/- 0.23 N, and 3.70 +/- 0.27 N. The retentive
      force of cpTi clasps was approximately half that of Co-Cr clasps for the same
      undercut depth.

PMID- 16900821
TI  - Marginal adaptation of 1 fiber-reinforced composite and 2 all-ceramic inlay fixed
      partial denture systems.
AB  - PURPOSE: The aim of this in vitro study was to evaluate the marginal adaptation
      and retention of inlay fixed partial dentures (IFPDs) made with 1 fiber
      reinforced composite and 2 different ceramic materials using quantitative
      scanning electron microscope analysis after thermal cycling and mechanical
      loading, which simulated approximately 5 years of oral service. MATERIALS AND
      METHODS: Eighteen IFPDs made with fiber-reinforced composite (SR Adoro/Vectris),
      zirconium oxide-TZP (Cercon), and magnesia partially stabilized zirconia (DC
      Leolux) covered with silica-based ceramics were tested in this study. The
      specimens were mechanically loaded in the vestibular cusp of the pontic element
      in a computer-controlled masticator with 1,200,000 half-sinusoid mechanical
      cycles of maximum 49 N each at a frequency of 1.7 Hz. A total of 3,000
      thermocycles at 5 degrees C and 55 degrees C, 2 minutes each, were performed
      simultaneously. The marginal adaptation was analyzed at the interface of the
      luting composite and the abutment inlay/onlay (CI) and at the interface of the
      tooth and the luting composite (TC). RESULTS: The percentages of continuous
      margin at the CI interface were 94.6 +/- 3.1 and 88 +/- 6.7 for Adoro/Vectris,
      92.9 +/- 5 and 85.7 +/- 6.1 for Cercon, and 96.2 +/- 2.1 and 82.2 +/- 9.8 for DC
      Leolux, respectively, before and after loading. The percentages of continuous
      margin at the TC interface were 86.7 +/- 6.7 and 62.5 +/- 16.4 for Adoro/Vectris,
      93.3 +/- 3.4 and 83.2 +/- 5.9 for Cercon, and 96.1 +/- 2.4 and 75.3 +/- 7 for DC
      Leolux. Statistically significant differences were found after loading between
      the fiber-reinforced composite and the 2 ceramic systems at the TC interface.
      CONCLUSION: Within the limitations of this experimental study with regard to the
      sample size and contacting vectors, the results showed that flexibility of the
      framework may play an important role in the marginal adaptation of the IFPDs.
      More rigid materials may transfer less stress to the margins, thus promoting a
      more stable adhesion to the dental tissues.

PMID- 16900822
TI  - Nasopharyngoscopy in palatopharyngeal prosthetic rehabilitation: A preliminary
      report.
AB  - PURPOSE: Prosthetic rehabilitation of speech disorders related to
      palatopharyngeal dysfunction is accomplished through separation of the oral and
      nasal cavities. The ability to achieve this separation is challenged when the
      disorder or defect involves the soft palate. Prosthetic rehabilitation of soft
      palate disorders and defects has traditionally relied on functional contouring of
      a prosthesis using functionally adapted impression materials. However, there are
      limitations to this process, particularly in its inability to visualize function
      as it relates to the prosthesis in a 3-dimensional space. The aim of this study
      was to address this limitation by describing outcomes related to the use of
      nasopharyngoscopy (NPS) for visualization of the velopharyngeal port during
      assessment and treatment of palatopharyngeal dysfunction. MATERIALS AND METHODS:
      A retrospective analysis of speech data was conducted for 5 patients who were
      assessed before treatment, after prosthetic intervention using conventional
      functional impression techniques, and after prosthetic intervention using NPS.
      Nasalance and velopharyngeal orifice area outcome measurements were collected for
      each patient at clinically predetermined intervals. Perceptual assessment of
      speech samples was performed as well. RESULTS: Improvements in speech function
      were observed for all patients after treatment with a prosthesis designed via a
      conventional functional impression technique; however, no patient showed normal
      values for nasalance or velopharyngeal orifice area. With the use of NPS to
      adjust the wax impression-derived prosthesis, both nasalance and velopharyngeal
      orifice area measurements for all patients were within normal limits. Similarly,
      perceptual judgment of speech found that normal resonance balance was obtained
      after use of NPS. CONCLUSION: The addition of NPS into prosthetic treatment for
      palatopharyngeal disorders shows promise for improved speech results.

PMID- 16900823
TI  - A 3-year prospective clinical and radiologic analysis of early loaded maxillary
      dental implants supporting single-tooth crowns.
AB  - In this study, 19 patients were treated with 36 Branemark System MK III TiUnite
      implants in the maxilla. Definitive implant-supported single crowns were
      delivered to patients 6 weeks after implant placement. Clinical and radiographic
      parameters were recorded at baseline, and at 1, 2, and 3 years. Both implant and
      prosthesis success rates were 94% after 3 years. The average marginal bone loss
      was 0.97 mm after 3 years. The results of this study indicate that 6-week early
      loading of TiUnite surface implants in the maxilla was reliable and predictable
      for this patient population and may offer an alternative to the standard loading
      protocol.

PMID- 16900824
TI  - In vivo wear of enamel by a lithia disilicate-based core ceramic used for
      posterior fixed partial dentures: first-year results.
AB  - PURPOSE: This study aimed (1) to test the hypothesis that no significant
      relationship exists between the magnitude of occlusal clenching force and wear
      rates of enamel opposing a new core ceramic (e.max Press, Ivoclar Vivadent) used
      in posterior fixed partial dentures (FPDs); and (2) to test the hypothesis that
      mean annual enamel wear by an experimental core ceramic is comparable to the mean
      annual enamel wear by enamel of 38 microm. MATERIALS AND METHODS: Baseline data
      were obtained for patients in addition to preliminary impressions of maxillary
      and mandibular teeth. Thirty ceramic FPDs were processed from a new core ceramic
      (e.max Press) that was hot pressed and glazed. Patients were recalled 1 year
      after cementation and evaluated using clinical criteria that included wear
      assessment of opposing teeth. Impressions were made of the opposing teeth with
      polyvinylsiloxane impression material and photographs were taken of intraoral
      occlusal contacts marked with articulating ribbon. Baseline casts and casts made
      at each recall exam of opposing dentitions were scanned using a 3-dimensional
      laser scanner (Laserscan 3D, Willytec) and evaluated for wear. A total of 21
      occlusal surfaces were analyzed for the presence of wear. RESULTS: Statistical
      analysis using a linear and quadratic model revealed no significant relationship
      between occlusal forces and wear rate assuming either a linear model (R2 = 0.018)
      or a quadratic model (R2 = 0.023). The maximum annual wear of enamel by the
      glazed core ceramic (e.max Press) was 88.3 microm, which is significantly greater
      than the annual enamel-by-enamel wear of 38 microm (P < .0001). CONCLUSION:
      Further analysis with a larger sample size is needed to determine the
      relationship between occlusal clenching force and wear rate and the influence of
      other factors that cause increased wear of enamel by opposing ceramic
      restorations.

PMID- 16900825
TI  - Metal-ceramic failure in noble metal crowns: 7-year results of a prospective
      clinical trial in private practices.
AB  - PURPOSE: The aim of this study was to evaluate the clinical performance of metal
      ceramic crowns placed in 10 private practices. MATERIALS AND METHODS: In this
      prospective clinical trial, 95 patients were provided with 190 noble-metal metal
      ceramic single crowns. RESULTS: The 7-year survival rates of the crowns were
      95.5% (target event: any removal), 99.5% (target event: removal because of
      defective veneer), and 92.4% (target event: metal-ceramic complication of any
      kind). No significant explanatory variables for metal-ceramic complications could
      be detected by bivariate and multivariate testing. The consequences resulting
      from metal-ceramic defects were of minor clinical significance in most cases.
      CONCLUSION: The findings support previous claims that metal-ceramic restorations
      perform very well clinically, including in practices outside academic
      environments.

PMID- 16900826
TI  - Repair bond strength of a resin composite to alumina-reinforced feldspathic
      ceramic.
AB  - This study compared the microtensile bond strength of a repair resin to an
      alumina-reinforced feldspathic ceramic (Vitadur-alpha, Vita) after 3 surface
      conditioning methods: Group 1, etching with 9.6% hydrofluoric acid for 1 minute
      plus rinsing and drying, followed by application of silane for 5 minutes; group
      2, airborne particle abrasion with 110-mm aluminum oxide using a chairside air
      abrasion device followed by silane application for 5 minutes; group 3, chairside
      tribochemical silica coating with 30-microm SiOx followed by silane application
      for 5 minutes (N = 30). Group 1 presented the highest mean bond strength (19.7 +/
      3.8 MPa), which was significantly higher than those of groups 2 (10 +/- 2.6 MPa)
      and 3 (10.4 +/- 4 MPa) (P < .01). Scanning electron microscope analysis of the
      failure modes demonstrated predominantly mixed types of failures, with adhesive
      and/or cohesive failures in all experimental groups.

PMID- 16900827
TI  - Tooth wear among psychiatric patients: prevalence, distribution, and associated
      factors.
AB  - PURPOSE: The purpose of this study was to evaluate the prevalence, distribution,
      and associated factors of tooth wear among psychiatric patients. MATERIALS AND
      METHODS: Tooth wear was evaluated using the tooth wear index with scores ranging
      from 0 to 4. The presence of predisposing factors was recorded in 143 psychiatric
      patients attending the outpatient clinic at the Prince Rashed Hospital in
      northern Jordan. RESULTS: The prevalence of a tooth wear score of 3 in at least
      one tooth was 90.9%. Patients in the age group 16 to 25 had the lowest prevalence
      (78.6%) of tooth wear. Increasing age was found to be a significant risk factor
      for the prevalence of tooth wear (P < .005). The occlusal/incisal surfaces were
      the most affected by wear, with mandibular teeth being more affected than
      maxillary teeth, followed by the palatal surface of the maxillary anterior teeth
      and then the buccal/labial surface of the mandibular teeth. The factors found to
      be associated with tooth wear were age, retirement and unemployment, masseter
      muscle pain, depression, and anxiety. CONCLUSION: Patients' psychiatric condition
      and prescribed medication may be considered factors that influence tooth wear.

PMID- 16900828
TI  - Why walkers slip: shine is not a reliable cue for slippery ground.
AB  - In a series of four studies, we investigated the visual cues that walkers use to
      predict slippery ground surfaces and tested whether visual information is
      reliable for specifying low-friction conditions. In Study 1, 91% of participants
      surveyed responded that they would use shine to identify upcoming slippery
      ground. Studies 2-4 confirmed participants' reliance on shine to predict slip.
      Participants viewed ground surfaces varying in gloss, paint color, and viewing
      distance under indoor and outdoor lighting conditions. Shine and slip ratings and
      functional walking judgments were related to surface gloss level and to surface
      coefficient of friction (COF). However, judgments were strongly affected by
      surface color, viewing distance, and lighting conditions--extraneous factors that
      do not change the surface COF. Results suggest that, although walkers rely on
      shine to predict slippery ground, shine is not a reliable visual cue for
      friction. Poor visual information for friction may underlie the high prevalence
      of friction-related slips and falls.

PMID- 16900829
TI  - Using verbal and blind-walking distance estimates to investigate the two visual
      systems hypothesis.
AB  - Verbal estimates of egocentric distance are usually too short at distances
      greater than several meters, yet blindfolded walking to previously viewed targets
      can be surprisingly accurate. We present evidence from three experiments for the
      existence of two visual pathways with differentencodings of perceived egocentric
      distance. We found that (1) blind-walking estimates of egocentric distance are
      consistently more accurate than verbal reports; (2) an indoor versus outdoor
      environment selectively influences verbal reports; and (3) wearing prism lenses,
      which displace the visual field vertically, selectively influences the blind
      walking estimates. We interpret these results in terms of the two visual systems
      hypothesis.

PMID- 16900830
TI  - Effects of hearing the past, present, or future during music performance.
AB  - Three experiments were performed to explore the effects of mismatches between
      actions (key-presses) and the contents of auditory feedback (pitch events) during
      music performance. Pianists performed melodies from memory during altered
      auditory feedback that was synchronized with key-presses but matched the pitch of
      other sequence events. Feedback direction was manipulated by presenting pitches
      that matched events intended for the past (delays; Experiments 1 and 3) or the
      future (prelays; Experiments 2 and 3). Feedback distance was manipulated by
      varying the absolute separation between the current event and the location of the
      feedback pitch. All alterations disrupted the accuracy of performance (pitch
      errors) more so than timing. Serial-ordering errors indicated confusions among
      proximal and metrically similar events, consistent with the predictions of an
      incremental planning model (Palmer & Pfordresher, 2003). Patterns of serial
      ordering errors suggested that performers compensate for the disruptive effects
      of altered feedback by changing event activations during planning.

PMID- 16900831
TI  - The field dependence/independence cognitive style does not control the spatial
      perception of elevation.
AB  - Earlier work described the presence of a significant connection between an
      individual's ability to disregard distracting aspects of a visual field in the
      classical rod-and-frame test (RFT), in which a subject is required to set a rod
      so that it will appear vertical in the presence of a square frame that is roll
      tilted from vertical, and in paper-and-pencil tests, in which the subject is
      required to find a hidden figure embedded in a more complex figure (the Embedded
      Figures Test [EFT]; see, e.g., Witkin, Dyk, Faterson, Goodenough, & Karp, 1962;
      Witkin et al., 1954; Witkin, Oltman, Raskin, & Karp, 1971). This has led to a
      belief in the existence of a bipolar dimension of cognitive style that is
      utilized in such disembedding tasks--namely, the extent to which an individual is
      dependent on or independent from the influence of a distracting visual field. The
      influence of an inducing visual field on the perception of elevation measured by
      the setting of a visual target to appear at eye level (the visually perceived eye
      level [VPEL] discrimination) has also been found to be correlated with the RFT.
      We have thus explored the possible involvement of the dependence/independence
      cognitive style on the VPEL discrimination. Measurements were made on each of 18
      subjects (9 of them female, 9 male) setting a small target to the VPEL in the
      presence of a pitched visual field across a range of six pitches from -30 degrees
      (topbackward) to +20 degrees (topforward) and on each of three tests generally
      recognized as tests of cognitive spatial abilities: the EFT, the Gestalt
      Completion Test, and the Snowy Pictures Test (SPT). Although there were
      significant pairwise correlations relating performance on the three cognitive
      tests (+.73, +.48, and +.71), the correlation of each of these three with the
      slope of the VPEL-versus-pitch function was not significant, as it was with the
      slope of the perception of visual pitch of the field (PVP)-versus-pitch function.
      VPEL, PVP, and a cognitive factor separated into three essentially independent
      factors in a multiple-factor analysis, with the three cognitive tests clustering
      at the cognitive factor, and with no significant loading on either of the other
      two factors. From the above considerations and a multiple-factor analytic
      treatment including additional results from this and other laboratories, we
      conclude that the cognitive-processing style held to be involved in the
      performance on the EFT and the perception of vertical as measured by the RFT is
      not general for egocentric space perception; it does not involve the perception
      of elevation.

PMID- 16900832
TI  - Signal detection theory, the approach of choice: model-based and distribution
      free measures and evaluation.
AB  - New and old methods of analyzing two-choice experiments with confidence ratings
      are evaluated. These include the theory of signal detectability (TSD), Luce's
      choice theory,nonparametric techniques based on areas under receiver-operating
      characteristic (ROC) functions, andmethods based on S' and omega, proposed by
      Balakrishnan and his colleagues. New methods for assessing the bias of a complete
      ROC function are proposed, together with an additional area-based measure of
      response bias. Area measures of both sensitivity and bias proved the most
      consistent. Response bias for a full ROC function was larger than bias at the cut
      point and also provided additional information. Participants showed voluntary
      control of bias for all measures except omega. Unequal variance versions of TSD
      and choice models gave similar fits to data, with the choice model closer to an
      equal variance version. Discrimination data from Balakrishnan (1999) formed the
      empirical test bed.

PMID- 16900833
TI  - Representations of scene layout can consist of independent, functional pieces.
AB  - A scene prime can induce a mental representation of layout that is functional in
      the sense that it facilitates the processing of depth relations in a subsequent
      same-scene target. Five experiments indicated that the representation can consist
      of separate and independent functional regions. In each experiment, primes with
      as many as four unrelated regions facilitated spatial processing within each
      region. The prime representations were functional despite structural
      discontinuity at region borders. The results indicate a limitation in the
      importance of structural constraint in representations of scene layout. However,
      when structural disruption occurred within regions that were perceived
      (Experiment 5), spatial processing was slowed. The results suggest that scene
      representation is more top down than is scene perception; the effects of
      structural disruption were overcome within representations, but not within
      perception.

PMID- 16900834
TI  - The aftereffects of ventriloquism: patterns of spatial generalization.
AB  - We examined how visual recalibration of apparent sound location obtained at a
      particular location generalizes to untrained locations. Participants pointed
      toward the origin of tone bursts scattered along the azimuth, before and after
      repeated exposure to bursts in one particular location, synchronized with point
      flashes of light a constant distance to their left/right. Adapter tones were
      presented straight ahead in Experiment 1, and in the left or right periphery in
      Experiment 2. With both arrangements, different generalization patterns were
      obtained on the visual distractor's side of the auditory adapter and onthe
      opposite side. On the distractor side, recalibration generalized following a
      descending gradient; practically no generalization was observed on the other
      side. This dependence of generalization patterns on the direction of the
      discordance imposed during adaptation has not been reported before, perhaps
      because the experimental designs in use did not allow its observation.

PMID- 16900835
TI  - Looking at object-substitution masking in depth and motion: toward a two-object
      theory of object substitution.
AB  - When attention is divided, a briefly presented target surrounded by four small
      dots is difficult to identify when the dots persist beyond target offset, but not
      when these dots terminate with the target. This object-substitution masking
      effect likely reflects processes at both the image level and the object level. At
      the image level, visual contours of the mask make feature extraction difficult.
      Recent data (Lleras & Moore, 2003) suggest that, at the object level, an object
      file is created for the target-plus-mask, and this single-object token later
      morphs into a single-object token containing the mask alone. In the present
      experiments, we used stimuli presented in 3-D space and apparent motion; the
      results indicate that object-substitution masking also arises when the mask and
      the target are represented in two separate object tokens and the mask token
      interferes with the target token.

PMID- 16900836
TI  - Visual, auditory, and cross-modality dual-task costs: electrophysiological
      evidence for an amodal bottleneck on working memory consolidation.
AB  - When two masked, attended targets (T1 and T2) are presented within approximately
      half a second of each other, report of T2 is poor, compared with when the targets
      are presented farther apart in time--a phenomenon known as the attentional blink
      (AB; Raymond, Shapiro, & Arnell, 1992). Some researchers have suggested that an
      amodal bottleneck on working memory consolidation underlies the AB (see, e.g.,
      Arnell & Jolicoeur, 1999). In the present work, T1 was masked, whereas T2 was
      unmasked. The modality of T1 (visual or auditory) and the modality of T2 (visual
      or auditory) were factorially manipulated across four experiments. For all
      modality combinations, T2's P3 event-related brain potential component was found
      to be delayed when T2 was presented soon after T1 (lag 3), compared with when T1
      and T2 were presented farther apart (lag 8). Results suggest that the working
      memory consolidation bottleneck is amodal in nature, and provide evidence that
      visual, auditory, and cross-modality ABs all result from a bottleneck on
      consolidation operations.

PMID- 16900837
TI  - Multistable syllables as enacted percepts: a source of an asymmetric bias in the
      verbal transformation effect.
AB  - Perceptual changes are experienced during rapid and continuous repetition of a
      speech form, leading to an auditory illusion known as the verbal transformation
      effect. Although verbal transformations are considered to reflect mainly the
      perceptual organization and interpretation of speech, the present study was
      designed to test whether or not speech production constraints may participate in
      the emergence of verbal representations. With this goal in mind, we examined
      whether variations in the articulatory cohesion of repeated nonsense words-
      specifically, temporal relationships between articulatory events--could lead to
      perceptual asymmetries in verbal transformations. The first experiment displayed
      variations in timing relations between two consonantal gestures embedded in
      various nonsense syllables in a repetitive speech production task. In the second
      experiment, French participants repeatedly uttered these syllables while
      searching for verbal transformation. Syllable transformation frequencies followed
      the temporal clustering between consonantal gestures: The more synchronized the
      gestures, the more stable and attractive the syllable. In the third experiment,
      which involved a covert repetition mode, the pattern was maintained without
      external speech movements. However, when a purely perceptual condition was used
      in a fourth experiment, the previously observed perceptual asymmetries of verbal
      transformations disappeared. These experiments demonstrate the existence of an
      asymmetric bias in the verbal transformation effect linked to articulatory
      control constraints. The persistence of this effect from an overt to a covert
      repetition procedure provides evidence that articulatory stability constraints
      originating from the action system may be involved in auditory imagery. The
      absence of the asymmetric bias during a purely auditory procedure rules out
      perceptual mechanisms as a possible explanation of the observed asymmetries.

PMID- 16900838
TI  - Voluntary eyeblinks disrupt iconic memory.
AB  - In the present research, we investigated whether eyeblinks interfere with
      cognitive processing. In Experiment 1, the participants performed a partial
      report iconic memory task in which a letter array was presented for 106 msec,
      followed 50, 150, or 750 msec later by a tone that cued recall of onerow of the
      array. At a cue delay of 50 msec between array offset and cue onset, letter
      report accuracy was lower when the participants blinked following array
      presentation than under no-blink conditions; the participants made more
      mislocation errors under blink conditions. This result suggests that blinking
      interferes with the binding of object identity and object position in iconic
      memory. Experiment 2 demonstrated that interference due to blinks was not due
      merely to changes in light intensity. Experiments 3 and 4 demonstrated that other
      motor responses did not interfere with iconic memory. We propose a new
      phenomenon, cognitive blink suppression, in which blinking inhibits cognitive
      processing. This phenomenon may be due to neural interference. Blinks reduce
      activation in area V1, which may interfere with the representation of information
      in iconic memory.

PMID- 16900839
TI  - Criteria for unconscious cognition: three types of dissociation.
AB  - To demonstrate unconscious cognition, researchers commonly compare a direct
      measure (D) of awareness for a critical stimulus with an indirect measure (I)
      showing that the stimulus was cognitively processed at all. We discuss and
      empirically demonstrate three types of dissociation with distinct appearances in
      D-I plots, in which direct and indirect effects are plotted against each other in
      a shared effect size metric. Simple dissociations between D and I occur when I
      has some nonzero value and D is at chance level; the traditional requirement of
      zero awareness is necessary for this criterion only. Sensitivity dissociations
      only require that I be larger than D; double dissociations occur whensome
      experimental manipulation has opposite effects on I and D. We show that double
      dissociations require much weaker measurement assumptions than do other criteria.
      Several alternative approaches can be considered special cases of our framework.

PMID- 16900840
TI  - Linking dynamical perceptual decisions at different levels of description in
      motion pattern formation: psychophysics.
AB  - The relationship between local-level motion detection and higher level pattern
      forming mechanisms was investigated with the motion quartet, a bistable stimulus
      for which either horizontal or vertical motion patterns are perceived. Local
      level perturbations in luminance contrast affected the stability of the perceived
      patterns and, thereby, the size of the pattern-level hysteresis obtained by
      gradually changing the motion quartet's aspect ratio. Briefly eliminating
      luminance contrast (so nonmotion was perceived during the perturbation)
      eliminated pattern-level hysteresis, and briefly increasing luminance contrast
      (so motion was perceived during the perturbation) increased pattern-level
      hysteresis. Partially reducing luminance contrast resulted in bistability during
      the perturbation; pattern-level hysteresis was maintained when motion was
      perceived, and eliminated when nonmotion was perceived. The results were
      attributed to local motion/nonmotion perceptual decisions in area V1 affecting
      the magnitude of the activation feeding forward to motion detectors in area MT,
      where the stability of pattern-level perceptual decisions is determined by
      activation-dependent, future-shaping interactions that inhibit soon-to-be
      stimulated detectors responsive to competing motion directions.

PMID- 16900841
TI  - Linking dynamical perceptual decisions at different levels of description in
      motion pattern formation: computational simulations.
AB  - A two-level dynamical model of motion pattern formation is developed in which
      local motion/ nonmotion perceptual decisions are based on inhibitory competition
      between area V1 detectors responsive to motion-specifying versus motion
      independent stimulus information, and pattern-level perceptual decisions are
      based on inhibitory competition between area MT motion detectors with orthogonal
      directional selectivity. The model accounts for the effects of luminance
      perturbations on the relative size of the pattern-level hysteresis effects
      reported by Hock and Ploeger (2006) and also accounts for related experimental
      results reported by Hock, Kelso, and Schoner (1993). Single-trial simulations
      demonstrated the crucial role of local motion/nonmotion bistability and
      activation-dependent future-shaping interactions in stabilizing perceived global
      motion patterns. Such interactions maintain currently perceived motion patterns
      by inhibiting the soon-to-be-stimulated motion detectors that otherwise would be
      the basis for the perception of an alternative pattern.

PMID- 16900842
TI  - [Incidental diagnosis of caecum adenocarcinoma due to retention of endoscopic
      videocapsule: a clinical case].
AB  - Capsule endoscopy is a new technique for the study of small intestine
      particularly in cases of obscure gastro-intestinal bleeding or chronic iron
      deficiency anemia. In our study we present a case of 62 years-old man with a
      chronic iron-deficiency anaemia developed at least six months before and
      refractory to iron therapy. The patient was submitted to upper gastro-intestinal
      endoscopy and to partial colonscopy due to abdominal adhesions for previous
      abdominal surgery. A capsule endoscopy was indicated to achieve a definitive
      diagnosis. Wich discosed an intestinal obstruction. So far a surgical resolution
      was indicated. The surgery revealed a stricturing neoplasia of the cecum in which
      the capsule endoscopy was retained.

PMID- 16900843
TI  - Plasma glucose level decreases as collateral effect of fermented papaya
      preparation use.
AB  - AIM: Fermented Papaya Preparation (FPP) is a natural healthy drug that has been
      commercially sold in Japan and Philippines. This nutricetive, bio-normalizer
      product has antioxidant action, inhibitory effect on oxidative DNA damage and
      tissue injury, being a potent OH scavanger. The wide use of FPP, expecially by
      elderly people, made us note an unknown collateral effect, i.e., blood sugar
      level dropping signs especially in the afternoon. The aim of the present work was
      to scientifically verify the possibility that individuals, who are taking the
      nutriceutical FPP, might have a decrease of plasma sugar levels. MATERIALS AND
      METHODS: For this purpose, 50 subjects, divided in two groups, were enrolled. The
      first group was made of 25 patients: 13 females and 12 males affected by type-2
      diabetes mellitus under treatment with the oral antidiabetic drug, glybenclamide.
      The control group included 25 clinically-healthy subjects: 16 females and 9
      males, matching in age. All subjects were given 3 grams of FPP daily, during
      lunch, for two months. RESULTS: The results of this study confirmed the empirical
      experience that FPP use can induce a significant decrease in plasma sugar levels
      in both healthy subjects and type 2 diabetic patients. This hypoglycaemic effect,
      associated with clinical signs, induced the diabetic patients to reduce the
      dosage of their antidiabetic oral therapy (in one patient the therapy was really
      suspended). CONCLUSIONS: In accordance with these results, the FPP administration
      is suggested as an adjuvant drug to join the oral antidiabetic therapy in type 2
      diabetes meltus.

PMID- 16900844
TI  - Proposal of a questionnaire to evaluate the foot in the rheumatic diseases.
AB  - OBJECTIVE: To compile a simple questionnaire, named 'Foot Health Questionnaire-1'
      (FHQ1), which would evaluate the state of the foot in rheumatic diseases, such as
      osteoarthritis (OA) and rheumatoid arthritis (RA). MATERIALS AND METHODS: Sixty
      three consecutive subjects entered the study: 25 with RA; 14 with OA; 10 with CTD
      and 14 healthy control subjects. RESULTS: It was possible to establish that the
      highest mean value of FHQ1 refers to RA patients (median FHQ1 value, 41) and OA
      patients (median FHQ1 value, 37) whereas for CTD patients the mean value was 14
      and for healthy subjects was = 0, as expected. It results that 72% of RA patients
      and 65% of OA patients enter classes III and IV of FHQ1, whereas 70% of CTD
      patients were in class I. CONCLUSIONS: An evaluation questionnaire regarding the
      algo-functioning of the foot could be a useful tool in routine rheumatologic
      clinical practice.

PMID- 16900846
TI  - [Scientific background and clinical implementation: three new proposals in
      coloproctology].
AB  - OBJECTIVE: The Authors underline three clinical problems in coloproctology: the
      surgical access to the anal canal, the lacking aspects of the actual
      classification of hemorrhoids, the difficult choice of the surgical treatment in
      case of coexisting III degrees and IV degrees degree of hemorrhoids. They propose
      a new anal retractor which enables the surgeon to better calibrate all the
      surgical procedures inside the anal canal and to operate alone without the help
      of another operator. A new computerized software is able to rapidly guarantee a
      numeric score for hemorrhoids which is repetable before and after treatment of
      the disease. The Authors present a new surgical technique defined of transfixed
      stichtes for the resolution of the most advanced stage of hemorrhoids. PATIENTS
      AND METHODS: The new anal retractor was used in fifthy consecutive patients
      operated on for proctological problems. A quickly computerized score coming from
      the new classification PATE 2000 Sorrento was evaluated in one hundred patients,
      while the surgical technique of transfixed stichtes was utilized in fifthy.
      RESULTS: All the surgical procedures performed with the new device were concluded
      without complications. The highest values of the score from PATE 2000 Sorrento
      always fit with the surgical treatment of the disease, while transfixed stitches
      gave dysuria in five patients, but a better quality of life was referred by 38
      over 50 patients treated. CONCLUSIONS: The Authors underline in this paper the
      results of the clinical implementation of these three new solutions in colon
      proctology.

PMID- 16900845
TI  - [Chronic osteomyelitis: one-step treatment].
AB  - PURPOSE: Chronic osteomyelitis is a surgical disease that require significant
      dedication from surgeons to eradicate. Osteomyelitis can result from a variety of
      etiologies but most often is a consequence of trauma (open fractures) to a long
      bone. This type includes osteomyelitis secondary to a contiguous focus of
      infection (after trauma and its surgical treatment: osteosynthesis). Here we are
      reporting one case of post-traumatic chronic osteomyelitis of the humerus.
      PATIENTS AND METHODS: A 34-years-old man presented with a post-traumatic chronic
      osteomyelitis due to an open fractur of the diaphysis humerus. We proposed a one
      step surgical treatment, including fistulectomy, sequestrectomy, opening of the
      proximal and distal intramedullary canal. Antimicrobial therapy should be
      followed by close observation and treatment with appropriate antibiotics.
      RESULTS: A clinical control at 30 days from the intervention revealed that: no
      secretion; negative cultured exam; second-intention healing of the skin.
      CONCLUSIONS: Treatment requires isolation of the pathogens, significant
      debridement for removal of all infective and necrotic material, both of bone
      origin and soft-tissue one. Is is necessary not to close the foci: in this way we
      leave an external drainage, which is able to provide a tissues sterilization by
      secretion drainage and by the effects of the systemic antimicrobial therapy. Our
      results indicate that this long-term problem can be solved by a one-stage
      procedure that provide spontaneous second- healing of the skin defects, excluding
      the bony and soft tissue reconstruction.

PMID- 16900847
TI  - [Psychopathology in epilepsy and pseudoepilepsy: preliminary results in our
      experience].
AB  - PURPOSE: Pseudoseizures or nonepileptic seizures (NES) are termed "nonepileptic
      psychogenic seizures" and account for approximately 20% of all intractable
      seizure disorders. These seizures are often misdiagnosed as true epilepsy,
      resulting in inappropriate, ineffective and costly treatment of many patients.
      Nowadays video-EEG monitoring have greatly improved the ability of specialists to
      correctly distinguish NES from epilepsy. Nevertheless, patients with NES do not
      always demonstrate obvious psychopathology. The aim of this study is to examine
      the complexity and severity of psychopathological features of patients with NES,
      in order to optimize strategies of intervention and appropriate long-term
      psychological and psychopharmacological treatment for these patients. MATERIALS
      AND METHODS: We evaluated three samples: patients with NES, patients with
      epilepsy and a control sample. Subjects with pseudoseizures and epileptic
      seizures have been randomly recruited from the Epilepsy Centre at the Neurology
      Institute of Catholic University of Sacred Heart of Rome. Seizures have been
      documented by the recording of spontaneous events with video-EEG, EEG, clinical
      observation and ictal examination. Each sample of patients has been tested using
      the Hamilton Rating Scale for Depression (HDRS), Dissociative Experience Scale
      (DES), Minnesota Multiphasic Personality Inventory-2 (MMPI-2) and Short Form
      Health Survey 36 (SF-36). RESULTS: 17 (4 M; 13 F) patients with NES, 13 (3 M; 10
      F) patients with epilepsy and 16 (4 M; 12 F) control subjects were recruited. Our
      preliminary results confirm previous researches showing that NES typically
      manifest between 20 and 30 years of age and that approximately a three-quarters
      of all patients are women. Besides, they confirm that psychosocial, environmental
      and intrapsychic mechanisms interact in the aetiology of NES: in particular, our
      preliminary results are consistent with the hypothesis that traumatic experiences
      are important precursors to the development and expression of NES. CONCLUSIONS:
      This study has yielded promising results and confirm the necessity to improve our
      knowledge about psychopathology of patients with NES. Psychiatrists and
      neurologists should work in equipe to guarantee an adequate treatment for a
      pathology too long set aside and almost ignored from clinical research.

PMID- 16900848
TI  - Microcarcinoma and incidental carcinoma of the thyroid in a clinical series:
      clinical behaviour and surgical management.
AB  - OBJECTIVES: Papillary thyroid microcarcinomas (PTM) have not yet an agreed
      clinical management. The Authors compared PTMs with papillary thyroid carcinoma
      of larger size (LPTC) and incidental and not-incidental carcinomas. MATERIALS AND
      METHODS: Review of clinical data of 67 patients (54 women, 13 men) prospectively
      stored in a standardised way in an electronic patient record system. RESULTS:
      There were 36 cases of microcarcinoma (53.7%). Differences were not significant
      between PTM and LPTC groups as to patients personal data, TNM and MACIS staging,
      nodal involvement (8.3% vs 19.3%) and multifocality (25% vs 38.7%) while capsular
      invasion was significantly higher in LPTC (25% vs 54.8%). Nineteen incidental
      tumors were detected at pathological examination and they were all
      microcarcinomas. They were smaller than the remaining 17 not-incidental
      microcarcinomas but showed a similar clinical behaviour. There were not cancer
      related deaths nor recurrences in the follow up period in any group. CONCLUSIONS:
      Despite the excellent prognosis of PTM, a subset of these tumours shows
      aggressive biological and clinical features, like nodal or capsular invasion and
      multifocality. Actually, with the exclusion of size, they do not show any
      relevant difference from differentiated thyroid carcinoma of larger size. Since
      predictive cytogenetic markers are still missing, their treatment should then be
      the same as for conventional thyroid cancers.

PMID- 16900849
TI  - [AIDS and forensic medicine. I. The framework of the debate].
AB  - The ethical debate regarding the AIDS is very rich both at the theoretical and
      practical level, but--unlike what it is happening for other sectors, e.g. the
      euthanasia--these two aspects are integrated, shaping a true interdisciplinary
      job of ethical evaluation, in which clinicians, medical examiners, ethicists,
      nurses, clinical psychologists, economists and politicians are met. The utilized
      methodology will be to identify the human act in the light of the patient's good
      and the common good of the society. These are strong references and broadly
      shared in general sense, but they become problematic if we want to identify, and
      we should have to do it, the contents of such "goods". The authors intend to
      appraise the quality of a Centre for Research and Healthcare for AIDS patients,
      also considering the "performance measures".

PMID- 16900850
TI  - Stiff person syndrome and motor mononeuropathy with conduction block: a singular
      association.
AB  - The "Stiff person syndrome"(SPS) is a rare dysimmune chronic neurological
      disorder, sometimes paraneoplastic, characterized by progressive stiffness,
      painful persistent or spasmodic muscle contractions, mostly involving spine and
      lower extremities. In 60 to 90 percent of cases, non-paraneoplastic forms are
      associated to the presence of anti-glutamic acid decarboxylase (anti-GAD)
      antibodies in the cerebrospinal fluid and in the serum, while anti-amphiphysin
      antibodies are frequently associated to paraneoplastic types. The relevant
      treatment consists of three basic approaches: increase in the inhibitory
      processes in charge of muscle activity control, re-modulation of the immune
      response, removal of any associated neoplasia. Indications regarding the efficacy
      of high-dose intravenous immunoglobulin (IVIG) also in this dysimmune pathology
      are on the increase. We described an unusual case of autoimmune SPS associated
      with an exclusively motor left peroneal nerve neuropathy, with conduction block,
      treated with high-dose intravenous immunoglobulin (IVIG), oral cyclosporine,
      sodium valproate, baclofen and diazepam.

PMID- 16900851
TI  - Circadian distribution of hematology variables in subjects with multiple
      sclerosis.
AB  - Hematology variables were measured in blood samples obtained every 3h (8/24h)
      from 10 multiple sclerosis (MS) patients and 34 healthy subjects and analyzed for
      circadian characteristics using the population multiple-components method. Red
      blood cell (RBC) and hemoglobin levels as well as hematocrits exhibited circadian
      rhythms with minimal amplitudes in healthy individuals and insignificant
      variability in the smaller group of MS patients. In contrast the total white
      blood cell (WBC) and platelet counts for MS patients and healthy individuals both
      showed significant circadian characteristics while the mean 24h WBC and platelet
      levels did not significantly differ between the two groups. When the different
      WBC subsets were examined independently, statistically significant circadian
      rhythms were seen for lymphocytes and eosinophils for both MS patients and
      healthy individuals and for neutrophils only in the latter. Moreover, the 24h
      mean levels of lymphocytes, basophils, and eosinophils were significantly higher
      for the healthy controls while those of monocytes were higher for the MS
      patients. However, of all the variables tested with significant circadian rhythms
      in both groups of individuals, only those of lymphocyte numbers exhibited
      different patterns with somewhat higher amplitude in healthy individuals and a
      peak level occurring over an hour after that of MS patients. These changes may be
      the reflection of a disturbance in the regulation of patterns of lymphocyte
      activity and migration in MS patients. In addition, the elevation in circulating
      monocytes in MS patients is consistent with the inflammatory nature of the
      disease.

PMID- 16900852
TI  - Some chronobiological considerations related to physical exercise.
AB  - Variables associated with physical activity show circadian rhythms in resting
      subjects; these rhythms have both exogenous (due to the individual's lifestyle
      and environment) and endogenous (due to the "body clock") components. During
      exercise, many of the rhythms persist, even though some show decreasing amplitude
      with increasing severity of exercise. Whilst the value of physical fitness is not
      disputed (for elite athletes, for individuals who just want to be physically fit,
      or for patients undertaking physical rehabilitation regimens), there are certain
      times of the day when special care is needed. These times are soon after waking-
      when there is the possibility of an increased risk of cardiovascular morbidity
      and damage to the spine--and late in the day--when there is an increased risk of
      respiratory difficulties. Since physical exercise is inextricably linked with
      thermoregulation, there are special considerations to bear in mind when exercise
      takes place in cold or hot environments. Further, due to the effects of the body
      clock, exercise and activity during night work and after time-zone transitions
      presents problems peculiar to these circumstances. In addition, the menstrual
      cycle affects physical performance, and these circatrigintan rhythms interact
      with the circadian ones. Bearing in mind these factors, advice that is based upon
      knowledge of circadian and circatrigintan rhythms can be given to all those
      contemplating physical activity. Chronobiologically, there is advantage in
      undertaking physical activity programmes towards the middle of the waking day and
      not at times when a sleep or nap has just been taken.

PMID- 16900853
TI  - [Indicators of educational assessment and prospects of improving university
      life].
AB  - INTRODUCTION: Five years after the establishment of the National Observatory for
      Assessment--now called National Committee for the Assessment of the University
      System--(L. 509/99), a critical analysis of the indicators chosen in relation to
      the aim suggested by the law itself becomes necessary. OBJECTIVE: To analyse the
      assessment system of the University Campus Bio-Medico as it has changed through
      time, in order to highlighten possible trends which have allowed a real
      improvement of the entire educational system. In these years our University has
      endeavoured to answer appropriately to the National Committee exhortations by
      creating its own system of self-assessment. This has strengthened the inner
      motivation to improve of all stakeholders of the educational process (students,
      teachers, tutors). The predominance of inner motivations on external ones is the
      essential feature in an university system which grants an educational model based
      on personal freedom and its related responsibility. This system, created and
      managed by the Department for Educational Research (DIE) of the University Campus
      Bio-Medico, is organized in three wider phases: planning of assessment tools and
      their administration; preparing the focus groups which address targeted groups of
      people so to evaluate the results and prepare new tools. RESULTS AND CONCLUSIONS:
      In our University assessment process certain values have acquired the structure
      of tracks along which it is possible to find concrete features: educational
      independence and planning governance as well as joint responsibility and
      cooperation. These are the key concepts which show the uniqueness and foundation
      of the entire educational system.

PMID- 16900854
TI  - The concept of "context" in health care: historical perspective and current
      views.
AB  - The concept of "Context" presents various aspects ranging from the emotive to the
      cognitive, from the structural and organisational to the methodological, from the
      social to the educational, and therefore merits consideration. Furthermore, the
      influence of the health context on clinical outcomes has recently had a rebound
      of attention in biomedical literature, given that the ability of clinicians to
      modify their professional practice is considered to be strongly influenced by the
      organisational and managerial milieu of their work. In the past attention was
      largely focussed on the ability of the environment to modify the health status of
      individuals and so to cause, or con-cause, diseases. There was instead a relative
      lack of interest in the influence of the health context on health operators, and,
      more importantly, in its effect on the relationship between patients and health
      operators and, in turn, of this latter relationship on clinical outcomes. This
      interest has recently been investigated and research has provided preliminary
      evidence that physicians adopting a friendly and reassuring approach are more
      effective than those who keep visits and counselling at a formal level. An
      awareness that many features of the concept of context in health care have been
      relatively little studied should address future research to clarifying
      scientifically the global role of context in health. The promising findings of
      the studies available, such as those here illustrated, point to the fact that
      valid research would be both feasible and effective.

PMID- 16900855
TI  - Renoprotective effect of renin-angiotensin system block: what has happened?
AB  - The Renin Angiotensin System block achieved by current available therapy
      (angiotensin II antagonism), despite undoubted beneficial effects, is associated
      to a persistent cardiovascular and renal mortality. During this angiotensin II
      antagonism, Renin Angiotensin System block is incomplete and angiotensin II break
      through. The Author analyses possible etiopathogenetic factors. Renin inhibition
      and Angiotensin-Converting Enzyme type 2 modulation are indicated and discussed
      as opportunities of Renin Angiotensin System block other than Angiotensin
      Converting Enzyme inhibitors and Angiotensin Receptor Blockers, that may render
      the Renin Angiotensin System block more quiescient.

PMID- 16900856
TI  - [Clinical guidelines for the management of gastrointestinal stromal tumors].
AB  - Treatment of gastrointestinal stromal tumors (GIST) has been revolutioned by the
      recently discovered molecular mechanism responsible for the oncogenesis of this
      disease. In addition, due to the rapid progress at molecular and clinical level
      observed in the last few years, there is a need to review the current state of
      the art in order to delineate appropriate guidelines for the optimal management
      of these tumors. A panel of experts from several specialities, including medical
      oncology, surgery, pathology, molecular biology and imaging, were invited to
      participate in a meeting to present and discuss a number of pre-selected
      questions, and to achieve a consensus according to the categories of the National
      Comprehensive Cancer Network (NCCN) and the Standard Options Recommandations
      (SOR) of the French Federation of Cancer Centers. Generally, consensus points
      were from categories 2A of the NCCN and B2 of the SOR. Conventional histologic
      examination with immunohistochemistry for CD117, CD34, SMA, S-100 and desmin is
      considered standard. Molecular analysis for the identification of KIT and PDGFRA
      mutation may be indicated in CD117-negative GIST. Complete tumor resection with
      negative margins is the optimal surgical treatment. Adjuvant imatinib should be
      considered an experimental approach. Neoadjuvant imatinib is also experimental,
      although its use may be justified in unresectable or marginally resectable GIST.
      Imatinib should be started in metastatic or recurrent disease, and should be
      continued until progressive disease or drug intolerance. In these cases,
      sunitinib can be used. The optimal criteria for the assessment and monitoring of
      GIST undergoing imatinib therapy are not well known, but they should include
      reduction in tumor size and disease stabilization, as well as reduction of tumor
      density on CT scan and metabolic activity on PET scan.

PMID- 16900857
TI  - [Methods of determination of total concentration of bacteria in atmospheric and
      indoor air].
AB  - Methods of evaluation of microbiological air pollution are not standardized in
      Poland. As a result of this status miscellaneous media and various methods of
      sedimentation of microorganisms on/or these media are applied in the studies. In
      practice it makes difficult (or even impossible) comparison of results published
      studies and expert's reports. To illustrate the range of the problem in the
      presented paper are shown results of measurements of total number of bacteria
      performed paralelly with: sedimentation and respiratory methods, three various
      media and clear different number of colony bacteria on Petri-dishes. Practical
      instructions concerned selection of measurements methods and interpretation of
      results are presented.

PMID- 16900858
TI  - [Microbiological quality of the air in "small gastronomy point"].
AB  - The aim of this work was the estimation of microbial contamination of the air in
      "small gastronomy point". The study included three places, which have been
      separated on the ground of their function: 1. area of subsidiaries, 2. area of
      distribution (sale and serving meal), 3. area of consumption. The total numbers
      of aerobic mesophilic bacteria, yeasts and moulds were determined by
      sedimentation method. Taxonomy units of fungal aerosol were also estimated. The
      samples of air were collected in 16 investigation points in the morning (8-8.30)
      and in the afternoon (14-14.30). Four series of measurements were carried out and
      in general 128 of air samples were tested. The results showed that numbers of
      bacteria, yeasts and moulds were variable and received respectively 30-3397, 0
      254 and 0-138 cfu x m(-3). Microbial contamination of air changed depending on
      area character (the highest average count of bacteria occurred in the air of
      consumption area and fungi in subsidiaries area), time of a day (contamination of
      the air increased in the afternoon) and determination date. Only in single
      samples the numbers of bacteria and fungi were higher than recommended level.
      Pigmentary bacteria had high participation in total count of bacteria and
      filamentous fungi were represented mostly by Penicillium sp. and Cladosporium sp.

PMID- 16900859
TI  - [Resistance of bacteria isolated from milking equipment to disinfectants].
AB  - The purpose of the study was a comparison of the sensitivity to three
      disinfectants of psychotropic and termotropic bacteria isolated from milking
      equipment. The study shows that psychotropic bacteria was more resistant on
      disinfectants used in experiments than termotropic. Bacteria's capability to
      acquire a resistant to disinfectants cause to search the new and more advance
      substances. Incorrect use of the antibacterial chemicals could accelerate this
      process.

PMID- 16900860
TI  - Ochratoxin a in maternal and foetal blood and in maternal milk.
AB  - Ochratoxin A (OA) levels were measured in blood serum of mothers foetuses and in
      mothers' milk. The mean concentration of OA in maternal serum was 1.14 ng/ml and
      in umbilical cord blood serum it was 1.96 ng/ml. The mean ratio of OA
      concentrations in maternal and foetal blood serum was 1.96. In maternal milk OA
      was found in 5 out of 13 studied samples. The mean intake of OA with mother's
      milk was not exceeding the tolerable daily intake for adults, nevertheless it was
      near 60% of TDI. The OA concentration ratio in maternal blood serum versus that
      in milk was 0.0058 on average. These results confirm the correlation between OA
      concentration maternal and foetal blood serum, and between OA concentration in
      maternal serum and milk.

PMID- 16900861
TI  - [Determination of chloramphenicol residues in animal tissues by LC-MS/MS method].
AB  - A liquid chromatographic method with mass spectrometric determination and
      identification (LC-MS/MS) for the determination of chloramphenicol (CAP) in
      tissues of animal origin was presented. Homogenized samples were extracted with
      ethyl acetate and evaporated to dryness followed by a clean-up using the liquid
      liquid distribution between acetonitryle and hexane. Chloramphenicol was
      determined by LC-MS-ESI-MS in negative mode. There was used Phenomenex column
      with the mixture of acetonitrile-water as a mobile phase. The method was
      validated according to the criteria of Decision Commission No 2002/657/EC.
      Samples were fortified at CAP levels between 0.1 and 0.45 ng/g with 5d-CAP as
      internal standard. Recoveries for the level 0.3 ng/g were in the range 76.3
      100.3%. Limit of decision (CCalpha) was between 0.137-0.205 ng/g. Limit of
      quantification (LOQ)--0.1 ng/g.

PMID- 16900862
TI  - [Nitrates (V) in drinking water as factor of a health risk for people in
      Podlaskie Voivodship].
AB  - The aim of this article was to evaluate of a health danger and to estimate the
      risk due to the presence of nitrates (V) in drinking water used by people in
      Podlaskie Voivodship. For research I used water specimens taken in 14 poviats
      (smaller administration districts) in Podlaskie Voivodship as part of drinking
      water quality monitoring in the years 2001-2003. Evaluation of danger of nitrates
      (V) taken in with drinking water by the population of Podlaskie Voivodship was
      carried out by comparing ADI (Acceptable Daily Intake) with value of EDI
      (Evaluated Daily Intake) and TMDI (Theoretical Maximum Daily Intake) Risk was
      estimated by calculating safety margin between ADI and EDI. On the basis of the
      obtained results it was stated that on the territory of Podlaskie Voivodship
      1.79% of urban population and 4.86% of rural population, was taking in nitrates
      (V) with water supplied by waterworks in doses below the safety margin. Nitrates
      (V) from drinking water in doses below the safety margin were taken in by
      population of 10 poviats, with the highest percentage of the population noted in
      the poviats of: Grajewo (10.97%), Augustow (10.77%) and Sejny (10.43%). Among the
      urban population the highest percentage noted in the Poviat of Augustow (9.46%),
      and among the rural population--in the Poviat of Grajewo (22.46%). The highest
      percentage of the population (69.97%) in Podlaskie Voivodship consumed nitrates
      (V) with drinking water supplied by waterworks in the range of the safety margin
      from 1 to 10, including 78.86% of urban population and 53.3% of rural population.
      It seems useful to continue the environmental research on the exposure of
      Podlaskie Voivodship inhabitants to nitrates by correlating the risk expressed by
      the safety margin with cancer epidemiology.

PMID- 16900863
TI  - [Nitrogen compounds in the well water of Sokolow Podlaski district].
AB  - In the year 2002 the quality of well waters was monitored in the area of Sokolow
      Podlaski district. Water samples collected four times per year from twenty once
      dug and drilled wells were examined for : NO3-, NO2-, NH4+, PO4(3-), Cl-, pH,
      total hardness and electrolytic conductivity. These studies showed that 58% out
      of all the analyzed water wells did not meet the requirements of standards
      related to nitrogen compounds content. During the whole period of the studies
      only 2 wells among 21 investigated met all the required standards as far as the
      examined parameters. These were the drilled wells of relevant localization and
      well enough isolated from all the sources of pollution.

PMID- 16900864
TI  - [The trace elements content in the selected vegetables from the Lublin area].
AB  - The ASA method was used to determine the content of copper, zinc, manganese and
      iron in the selected vegetables (lettuce, radish, spinach, chives, sorrel)
      obtained from the following allotments: Lublin centre, the city surrounding and
      from the marketplace and the supermarket. The vegetables bought at the
      supermarket were characterized higher concentration of copper and zinc in
      comparison with the vegetables coming from the allotments in the Lublin centre,
      the city surrounding and also from the marketplace. All the tested vegetables
      were rich in iron, however accumulated insignificant amount of copper. The trace
      elements content in the tested vegetables were not significant and were not
      harmful to people's health.

PMID- 16900865
TI  - The effect of socio-economic and demographic determinants on the pattern of
      consumption of rural adolescents.
AB  - The aim of this study was to determine the effect of selected socio-economic and
      demographic determinants (the number of children in the family, father's
      education, standard of living, sex and age) on the pattern of consumption in
      adolescents occupying rural areas of the central-eastern Poland. The study
      included 564 boys and 548 girls 10-15-years-old. Data on the socio-economic
      status and dietary habits were collected by means of a diagnostic survey. Dietary
      habits were determined based on a single 24-hour recall. Results obtained were
      compared with the RDA for Polish people. The effect of socio-economic and
      demographic determinants on the pattern of consumption were mogenous clusters
      each of which corresponded to a specific pattern of consumption. It was
      demonstrated that standard of living and the father's education exerted a
      significant effect on the pattern of consumption in adolescents examined. This
      effect was hot indicated for the number of children in the family, age and sex.

PMID- 16900866
TI  - [The consumption frequency and the caloric value of breakfasts among the school
      children and teenagers].
AB  - The aim of this study was to make a customary frequency analysis of breakfast and
      lunch consumption among the children and teenagers from the rural environment,
      and a comparison of the caloric value of breakfasts and other meals eaten by the
      rural and urban teenagers during their stay at school. Breakfast was consumed by
      52.8% to 65.85% of the tested from the rural environment. Among the upper
      secondary school students, the boys consumed their breakfast more often than the
      girls. A customary frequency lunch consumption in the rural population has
      lowered with age. It was always consumed by over 52% of the primary school
      students and only 31.9% of the lower secondary school students. The breakfasts of
      the caloric value lower than 20% in comparison with daily food rations were eaten
      by 43.74% of the students, and the tested from the urban area in this group made
      a higher percentage. Any vital differences in the breakfast caloric values
      depending on the place of living were not observed. More than 20% of the students
      in total had consumed neither a product nor a meal at school the day before the
      test was carried out. A higher percentage in this group made the boys from the
      urban area, but the rural boys at the age of 10.5 accepted a considerably smaller
      amount of energy from the food as compared with their peers from the city.

PMID- 16900867
TI  - [Assessment of mammographic units in Poland in the view of current requirements
      of radiation protection regulations].
AB  - The aim of mammography examination is to discover as soon as possible any
      structural changes in a breast tissue. Every X-ray examination exposure the
      patient to the radiation as it takes place in mamnography images might be a cause
      of cancer. In this publication the dynamics growth of mammnography units number
      in Poland in years 1995,1997 and 2002 has been analyzed. The distribution of
      mammography units in Poland has been examined. The places of mammography units
      exploitation in regard to the type of health service institution has been
      determined. In this publication the manufacturers and the age of mammography
      units as a prerequisite to determine whether the specified mammography unit
      complies with the actual requirements in radiation protection regulations have
      been taken into consideration. The mammography laboratory equipment for providing
      quality control and the method of developing X-ray films has been also analyzed.
      It has been ascertained that about 25 % of mammography units do not comply with
      current technical requirements and they should be withdrawn from exploitation.
      However, it should be pointed out that there were only 554 mammography units in
      Poland at the end of year 2002. Their unequal distribution do not provide
      satisfactory availability to examinations for patients. As a result of this, the
      principal method of withdrawing them from exploitation should be replacing the
      time-worn the X-ray apparatuses with the new ones.

PMID- 16900868
TI  - 100,000 lives and counting.

PMID- 16900869
TI  - Evolution of the supply chain exchange. Interview by Robert Neil.

PMID- 16900870
TI  - Store-bought lessons.

PMID- 16900871
TI  - Back to supply chain basics.

PMID- 16900872
TI  - Cleaner data, better business.

PMID- 16900873
TI  - Prevent nosocomial infections at the start.

PMID- 16900874
TI  - IT implementation challenges and solutions. Roundtable discussion.

PMID- 16900875
TI  - Trend shows growing orthopedic surgery case load. Will surgeons be able to keep
      up?

PMID- 16900876
TI  - Organizations collaborate to mitigate pandemic. Software to track and predict
      spread of disease.

PMID- 16900877
TI  - Understanding the supply chain as a component of patient care.

PMID- 16900878
TI  - STR markers for kinship analysis.
AB  - The analysis of short tandem repeats is a widely used method to estimate
      relatedness between closely related populations or individuals. The AmpFlSTR PCR
      Amplification Kit has 15 highly variable autosomal markers of tetranucleotide
      repeats and is principally made to identify individuals and first- or second
      degree relatives. However, in many studies one is searching for individuals who
      are related through more than one generation. We wanted to test whether the
      amplification kit can also be used to identify more distantly related
      individuals. Therefore we compared 16 different methods that calculate genetic
      distance with regard to each method's ability to cluster more distantly related
      individuals from two test families. Among all the tested methods Nei et al.'s
      (1983) DA distance performed well in clustering family members within a group of
      unrelated individuals for a broad range of scenarios. However, second-degree
      relatives were difficult to cluster with any of the examined methods when other
      family members were absent. With a simulation we further estimated how many
      markers would actually be needed to detect a certain degree of relatedness.
      According to this simulation, one would need at least 123 independent
      microsatellite markers to detect third-degree relatives with 90% probability. In
      conclusion, the 15 STR markers in the amplification kit are suitable for
      detecting only very closely related individuals or entire families.

PMID- 16900879
TI  - MtDNA of Fulani nomads and their genetic relationships to neighboring sedentary
      populations.
AB  - Despite the large size of the contemporary nomadic Fulani population (roughly 13
      million people), the genetic diversity and degree of differentiation of Fulanis
      compared to other sub-Saharan populations remain unknown. We sampled four Fulani
      nomad populations (n = 186) in three countries of sub-Saharan Africa (Chad,
      Cameroon, and Burkina Faso) and analyzed sequences of the first hypervariable
      segment of the mitochondrial DNA. Most of the haplotypes belong to haplogroups of
      West African origin, such as L1b, L3b, L3d, L2b, L2c, and L2d (79.6% in total),
      which are all well represented in each of the four geographically separated
      samples. The haplogroups of Western Eurasian origin, such as J1b, U5, H, and V,
      were also detected but in rather low frequencies (8.1% in total). As in African
      hunter-gatherers (Pygmies and Khoisan) and some populations from central Tunisia
      (Kesra and Zriba), three of the Fulani nomad samples do not reveal significant
      negative values of Fu's selective neutrality test. The multidimensional scaling
      of FST genetic distances of related sub-Saharan populations and the analysis of
      molecular variance (AMOVA) show clear and close relationships between all pairs
      of the four Fulani nomad samples, irrespective of their geographic origin. The
      only group of nomadic Fulani that manifests some similarities with geographically
      related agricultural populations (from Guinea-Bissau and Nigeria) comes from
      Tcheboua in northern Cameroon.

PMID- 16900880
TI  - MtDNA haplogroup analysis of black Brazilian and sub-Saharan populations:
      implications for the Atlantic slave trade.
AB  - Seventy individuals from two African and four black Brazilian populations were
      studied for the first hypervariable segment of mtDNA. To delineate a more
      complete phylogeographic scenario of the African mtDNA haplogroups in Brazil and
      to provide additional information on the nature of the Atlantic slave trade, we
      analyzed our data together with previously published data. The results indicate
      different sources of African slaves for the four major Brazilian regions. In
      addition, the data revealed patterns that differ from those expected on the basis
      of historical registers, thus suggesting the role of ethnic sex differences in
      the slave trade.

PMID- 16900881
TI  - The Khatri Sikh Diabetes Study (SDS): study design, methodology, sample
      collection, and initial results.
AB  - Non-insulin-dependent diabetes mellitus, or type 2 diabetes (T2DM), has become a
      major public health problem in India. The high prevalence, relatively young age
      of onset, and strong familial aggregation of T2DM in some Indian communities
      remains to be explained. Many of the traditional risk factors established for
      European populations do not appear to be present in Asian Indians. Phase I of the
      Sikh Diabetes Study (SDS) was launched to build the population resources required
      to initiate a large-scale genetic epidemiological study of diabetes in an Asian
      Indian population. The SDS is focused on the Khatri Sikh population of North
      India. In all, 1,892 subjects were enrolled to participate in the family-based
      study; 1,623 of these subjects belong to 324 families, each of which has at least
      2 siblings affected with T2DM. The sample included 1,288 individuals affected
      with T2DM (siblings, parents, or relatives) and 335 unaffected siblings, parents,
      or relatives. The remaining 269 subjects were unrelated nondiabetic control
      subjects, including unaffected spouses of probands or siblings. This primarily
      nonvegetarian, nonsmoking endogamous caste group has presented an unusual
      clinical picture of uneven distribution of adiposity and a high rate of T2DM with
      secondary complications. Such well-characterized population isolates may offer
      unique advantages in mapping genes for common complex diseases.

PMID- 16900882
TI  - Heterogeneity of apolipoprotein E polymorphism in different Mexican populations.
AB  - Mexico has approximately 100 million inhabitants. Most of the urban Mexican
      population has been considered mestizo (Indian and Spanish descent), whereas the
      Indian population predominates in rural areas and small towns in the countryside.
      In this study we analyzed the apolipoprotein E (APOE) polymorphism in Guadalajara
      (the second largest metropolitan area of Mexico) and its surrounding areas, two
      adjoining states (Nayarit and Durango), and an Indian town (Huichol Indians) from
      western Mexico. APOE*3 was the most common allele, and APOE*3/*3 was the most
      common genotype in all populations studied. Guadalajara revealed the highest
      frequency of the APOE*2 allele (7.8%); the frequency decreased in the rural area
      (4.4%), followed by Nayarit (1.6%), and was absent in Durango and in the
      Huichols. On the contrary, the lowest frequency of the APOE*4 allele was in
      Guadalajara (8.4%); the frequency increased in the rural area (9.3%), in Nayarit
      and Durango (11.5% and 11.7%), and reached a high frequency in the Huichol
      Indians (28%). The distribution of the APOE allele in the western population of
      Mexico is similar to those described in Mexican American migrants living in the
      United States but is different from those populations living in Mexico City. This
      study shows the heterogeneity of the Mexican population, where the frequency of
      the APOE*2 allele is higher in Guadalajara than in other urban areas of Mexico
      and is similar to frequencies described in the Caucasian population. On the
      contrary, the Huichols revealed the highest frequency of the APOE*4 allele in
      Mexico and in the Americas. This information could be useful for the study of
      dyslipidemias associated with chronic diseases and as markers of ethnic variation
      in the Americas.

PMID- 16900883
TI  - Association between morbidity and skeletal biomarkers of biological aging.
AB  - The Osseographic Scoring System (OSS) is a synthetic measure of skeletal aging
      that combines osteoporotic and osteoarthritic changes of the hand. The OSS is
      used to evaluate biological age in a population. The aim of the present study was
      to evaluate the association between certain chronic morbidities and the skeletal
      biomarker of biological aging. We performed a population-based study on a large
      sample of individuals who were receiving no medications to treat or prevent
      chronic morbidities [668 male (age 18-89 years) and 608 female (age 18-81 years)
      Chuvashians]. Morbidity data obtained from the individuals' medical records was
      sorted into 16 categories. A one-way ANOVA was used to elucidate the association
      between morbidity and age-adjusted OSS score. Statistically significant
      differences between means of OSS scores in affected vs. nonaffected individuals
      were found in the rheumatic diseases group. Ischemic heart disease, pulmonary
      diseases, traumatic brain injuries, and gynecological diseases also showed
      differences; however, after correction for multiple testing, the results were
      statistically nonsignificant. We conclude that individuals who suffer from the
      mentioned chronic morbidities will show a higher degree of skeletal aging.
      Further research is needed to clarify the biological mechanisms of association
      between certain types of morbidities and changes in skeletal aging.

PMID- 16900884
TI  - Collection of pedigree data for genetic analysis in isolate populations.
AB  - Pedigree data are useful for a wealth of research purposes in human population
      biology and genetics. The collection of extended pedigrees represents the most
      powerful sampling design for quantitative genetic and linkage studies of both
      normal and disease-related quantitative traits. In this paper we outline an
      approach for collecting pedigree data in stable isolate populations. As an
      example, the pedigree for the Jirel population, which was obtained using the
      methods presented, is described. The Jirel pedigree contains 2,000 study
      participants and more than 62,000 pairwise relationships that are informative for
      genetic analysis. Once such pedigrees are genetically characterized by a genome
      scan for a given trait, they become an invaluable resource for future genetic
      studies of any quantitative trait.

PMID- 16900885
TI  - Insertion-deletion polymorphism in the angiotensin-converting enzyme (ACE) gene
      among Sudanese, Somalis, Emiratis, and Omanis.
AB  - The angiotensin-converting enzyme (ACE) gene in humans contains an insertion
      deletion polymorphism in its intron 16. Because of its involvement with the renin
      angiotensin system, the insertion-deletion polymorphism of the ACE gene has been
      widely investigated in different populations and in case-control studies.
      However, similar studies for Arab populations are limited in number. Therefore we
      have investigated the frequencies of the *I and *D alleles of the ACE gene among
      Sudanese, Somalis, and Arab nationals of the United Arab Emirates and Oman using
      previously described methods. Our data indicate a preponderance of the *D allele
      among the Arab and African populations studied (Sudanese, 0.64; Somalis, 0.73;
      Emiratis, 0.61; and Omanis, 0.71).

PMID- 16900886
TI  - Linkage disequilibria and haplotype structure of four SNPs of the interleukin 1
      gene cluster in seven Asian Indian populations.
AB  - Variation at four single nucleotide polymorphism (SNP) sites of the interleukin 1
      (IL1) gene cluster was investigated among 280 unrelated individuals, representing
      7 caste groups from the state of Karnataka, India, and one European American
      community of Boston, Massachusetts. Allele and haplotype frequencies, strength of
      linkage disequilibrium, and signatures of recombination varied considerably among
      populations. Variable community sizes and traditions of consanguinity may account
      for the observed variation.

PMID- 16900887
TI  - Haptoglobin gene promoter polymorphism and haplotypes are unique in different
      populations.
AB  - We investigated the distribution of haptoglobin (HP) alleles and haplotypes among
      Africans (Ghanaians), Europeans (from South Africa), and Chinese. HP*1F was
      present only in Africans and Europeans, whereas HP*del was unique to Chinese. Six
      base substitutions at the promoter region were population specific. Only 3 out of
      18 haplotypes were shared among the populations. A probable application of HP in
      human population genetics appears legitimate.

PMID- 16900888
TI  - Detection and measurement of oral malodour in periodontitis patients.
AB  - BACKGROUND & OBJECTIVES: Malodour has been correlated with the concentration of
      volatile sulphur compounds produced in the oral cavity by metabolic activity of
      bacteria colonizing the periodontal sites and the dorsum of the tongue. The aim
      of this study was to detect malodour in mouth air organoleptically and using a
      portable sulphide monitor and to correlate it with the clinical parameters,
      halitosis linked toxins and BANA, using tongue and subgingival plaque samples.
      The halitosis grading is also correlated with the microbial colonies of the
      subgingival plaque sample. METHODS: 20 patients with chronic periodontitis with 5
      7 mm pocket depth, radiographic evidence of bone loss and presence of oral
      malodour participated in this study. Assessment of mouth air was done
      organoleptically and by using a portable sulphide monitor. The clinical
      parameter, plaque index (PI), gingival index (GI), gingival bleeding index (BI),
      were obtained from all the areas. Samples for BANA and to detect halitosis linked
      toxins were taken from the dorsal surface of the tongue and periodontal pockets
      ranging 5-7 mm. Halitosis related microbial colonies were identified using
      anaerobic culturing from the subgingival plaque. RESULTS: The scores of PI, GI,
      BI and sample that tested positive for halitosis linked toxins and with the
      halitosis grading were not significant. The presence of tongue coating and the
      halitosis grading and toxin levels were significant. BANA has shown to be non
      contributory due to technical problems. Anaerobic culture has shown to identify
      Streptococcus, Bacteroides, Fusobacterium, Porphyromonas and Prevotella colonies.
      INTERPRETATION & CONCLUSION: The results confirmed that there was no correlation
      between the clinical parameters, halitosis linked toxins and halitosis grading.
      The microbial colonies have shown to correlate with the presence of oral
      malodour.

PMID- 16900889
TI  - Anatomical variations of mandibular premolars in Chennai population.
AB  - AIM: To analyse the prevalence of anatomical variations of mandibular premolars
      in Chennai population. METHODOLOGY: It was observed, during the routine treatment
      of mandibular premolars that aberrations were becoming common. This necessitated
      an encompassing study on 500 patients, evaluating the occurrence of these
      aberrations. The parameters of this study included sex predilection, unilateral/
      bilateral occurrences, and comparison of the incidence of anatomical variations
      in mandibular first and second premolar canal configuration. The study pattern
      was designed to observe these premolars using Radiovisiography (RVG) in different
      angulations to highlight the anatomical aberrations. The results were subjected
      to statistical analysis, which were performed using SPSS (Statistical Package for
      Social Science) statistical program version 10.0.5. Descriptive statistics were
      computed for all the variables. RESULT: The present study revealed high incidence
      of anatomical aberrations in mandibular premolars among Chennai population. Out
      of the 500 patients studied, 123 patients [24.6%] showed anatomical variance in
      the canal configuration. There was high incidence of Vertucci's Type IV canal
      configuration as compared to Type V, Type II and Type VIII in the descending
      order of occurrence. CONCLUSION: Within the limitations of this in-vivo study, it
      was inferred that the incidence of aberrations in the canal configuration of
      mandibular premolars is common and due considerations are to be given during
      endodontic intervention.

PMID- 16900890
TI  - Oral healthcare for elderly: identifying the needs and feasible strategies for
      service provision.
AB  - The aim of the present study was to assess the oral health practices, status and
      treatment needs of the rural elderly in national capital territory of Delhi. An
      effort was also made to identify patterns of utilization of dental services and
      test alternate strategies for service provision. A total of 96 elderly subjects
      (47 males and 49 females) in 5 rural areas were interviewed and clinically
      examined using Basic Oral Health Survey criteria of W.H.O. This was followed by a
      community trial in which the 5 villages were divided into control and test
      groups. Results of the survey found that both traditional as well as modern oral
      health practices co-exist in the rural community. Dental services were available
      to a majority (mostly through private sector), and edentulousness was a condition
      of primary concern among the elderly as a result of unmet treatment needs for
      dental caries and periodontal diseases. Age was a variable that was statistically
      significantly associated with edentulousness (p=0.005). Results of the community
      trial showed that higher utilization of care can be achieved by providing on-site
      dental care as compared to referring cases to tertiary care centers. Nevertheless
      provision of treatment alone is not a suitable policy recommendation since many
      elderly did not avail care even at on-site community dental health programmes
      that were operated free of cost. This emphasizes the need of health education
      over treatment in order to empower the elderly, especially the non-ambulatory
      patients, to practice prevention and develop favourable attitudes towards
      accepting prompt treatment at primary health care level.

PMID- 16900891
TI  - Correlation of clinical and MRI findings of tempero-mandibular joint internal
      derangement.
AB  - The most common clinical features of tempero-mandibular joint internal
      derangement are correlated with the MRI findings of shape of the disc in an
      attempt to find the etiology of tempero-mandibular joint internal derangement. In
      this study, the clinical parameters of pain, muscle tenderness, clicking with in
      the joint (like early, middle and late) are correlated with the MRI findings of
      disc shapes. (like biconcave, thick, lengthened, folded, adhesion). The study
      reveals any trauma that leads to muscle tenderness results in internal
      derangement of tempero-mandibular joint.

PMID- 16900892
TI  - Evaluation of physiological and behavioral measures in relation to dental anxiety
      during sequential dental visits in children.
AB  - Anxiety is a special variety of fear, experienced in anticipation of threatening
      stimuli. While some research workers have said that the response of a child
      improves with the number of visits, many have felt otherwise. The present study
      is yet another effort to find the patterns of anxiety in children during
      sequential dental visits. The main aim was to determine the physiological and
      behavioral variations during sequential dental visits and its impact on age and
      sex. The study was conducted at the outpatient Department of Pedodontics and
      preventive dentistry, Meenakshi Ammal Dental College and Hospital, Chennai to
      evaluate the physiological and behavioural measures of stress and anxiety in
      children. One hundred and fifteen children, between four and eleven years of age
      who reported for dental treatment were selected for the study.

PMID- 16900893
TI  - A modified double pedicle graft technique and other mucogingival interceptive
      surgeries for the management of impacted teeth: a case series.
AB  - Maxillary canine is one of the most common teeth that are impacted. This accounts
      for 1-2% of all patients who attend orthodontic treatment. The key to achieve
      maximal eruption of these teeth is their surgical exposure and the role of
      periodontist in such situations is to provide a functional and satisfactory width
      of attached gingiva on the labial surface. There are different techniques to
      surgically expose the impacted teeth, namely--gingivectomy technique, apically
      positioned flap, closed eruption technique, modified apically positioned flap,
      double pedicle flap and free gingival graft. Selection of the procedure is
      dependent on the positioning of the tooth in relation to mucogingival junction
      and attached gingiva. In the present case series we describe three different
      techniques for uncovering of impacted teeth, which are apically positioned flap,
      closed eruption technique and a modified double pedicle graft specially planned
      for the situation. These procedures when selected diligently using sound
      selection criteria will create adequate width of attached gingiva which minimizes
      or eliminates the future mucogingival problems.

PMID- 16900895
TI  - Desmoplastic ameloblastoma: report of a unique case and review of literature.
AB  - Desmoplastic Ameloblastoma is a rare variant of ameloblastoma. 90 cases of
      desmoplastic ameloblastoma have been reported so far in literature. We are
      presenting a rare case of desmoplastic ameloblastoma in the ramus region of
      mandible with regards to its clinical and radiographical viewpoints. Only one
      other case of desmoplastic ameloblastoma has been reported in the ramus region of
      mandible of the 90 cases that we have reviewed. Review of literature has revealed
      the tumour to most commonly occur in the 3rd to 5th decade of life with a high
      preponderance of Japanese males. The anterior region of either jaw was most
      commonly found to be affected. Radiological appearance was most commonly of a
      mixed radio-lucent/radio-opaque type with a high incidence of poorly defined
      borders. However our case differed from the reviewed cases as it was found to be
      a unilocular lesion with well defined borders. Histopathological findings of our
      case were consistent with the hisotpathological appearance of the reviewed cases
      and showed extensive stromal desmoplasia and small tumour nests of odontogenic
      epithelium scattered in stroma.

PMID- 16900894
TI  - Primary oral tuberculosis: report of two cases.
AB  - Oral lesions of tuberculosis though uncommon, are seen in both the primary and
      secondary stages of the disease. In secondary tuberculosis, the oral
      manifestations may be accompanied by lesions in the lungs, lymph nodes, or in any
      other part of the body and can be detected by a systemic examination. Primary
      oral tuberculosis may present as a diagnostic challenge for the clinician. Here
      we report two patients with primary tuberculosis in the oral cavity who presented
      to the dental department, were diagnosed and referred for medical management.

PMID- 16900897
TI  - Right-source, right-size, right-staff for most effective practice.

PMID- 16900896
TI  - Nevoid basal cell carcinoma syndrome.
AB  - Binkley and Johnson first reported this syndrome in 1951. But it was in 1960,
      Gorlin-Goltz established the association of basal cell epithelioma, jaw cyst and
      bifid ribs, a combination which is now frequently known as Gorlin-Goltz syndrome
      as well as Nevoid Basal Cell Carcinoma Syndrome (NBCCS). NBCCS is inherited as an
      autosomal dominant trait with high penetrance and variable expressivity. NBCCS is
      characterized by variety of cutaneous, dental, osseous, opthalmic, neurologic and
      sexual abnormalities. One such case of Gorlin-Goltz syndrome is reported here
      with good illustrations.

PMID- 16900898
TI  - For efficient messaging, throw out the in-box.

PMID- 16900899
TI  - Budget reconciliation affects payments and provisions for medical practices.

PMID- 16900900
TI  - Don't let consumer-driven health plans run over your practice.

PMID- 16900901
TI  - Click--there goes another paper-based practice.

PMID- 16900902
TI  - Now, wait just a minute.

PMID- 16900903
TI  - You're on the team!
AB  - There's a new role emerging for today's medical practice administrator: member of
      the organization's clinical team. Although the tasks of an administrator still
      stop at the doorway of the exam or operating room, what he or she does everywhere
      else in the practice is increasingly recognized as a direct aid to clinical
      quality. Nonclinicians can--and should--try to influence the patient care
      process. In addition to understanding their roles in risk management and patient
      safety, administrators should help ensure a courteous, competent and
      compassionate administrative staff.

PMID- 16900904
TI  - From plan to action.
AB  - A strategic plan is your organizational touchstone Given the rapid rate of change
      in health care, your practice's capacity to succeed is based on its ability to
      adapt quickly; this, in turn, relies on the level of detail in the operational
      plan. A well-devised and detailed plan will enable your practice to navigate the
      waters of industry change. An operational plan begins with the practice's vision,
      values and mission.

PMID- 16900905
TI  - What does it take to lead?
AB  - Health care management today overflows with complex challenges and opportunities
      that require health care executives to possess extraordinary leadership skills.
      An extensive project--in which MGMA participated--to define the leadership
      competencies in health care has created a leadership competency directory
      comprising 300 competencies within five domains.

PMID- 16900906
TI  - Stealing your good name.
AB  - Identity theft--the fastest-growing crime in America--has infiltrated the health
      care sector. The medical practice administrator plays a key role in protecting a
      group's employees and patients from this peril. The vast amounts of patient data
      stored by health care organizations--paper and electronic--can lure identity
      thieves. The daunting task of developing and implementing policies to safeguard
      protected health information for patients, physicians and employees frequently
      falls to the practice manager.

PMID- 16900907
TI  - The comeback kid.

PMID- 16900909
TI  - Pharma exec takes exception to pain article assertions.

PMID- 16900910
TI  - A difficult conversation, but one that benefits others.

PMID- 16900912
TI  - Lemonade is an option for some hypocitraturic patients.

PMID- 16900913
TI  - What's causing that gut pain?

PMID- 16900914
TI  - Psychotropics.

PMID- 16900915
TI  - Keeping pace with cardiac devices.

PMID- 16900916
TI  - Patient information. Living with an implantable cardiac device.

PMID- 16900917
TI  - Nursing in Iraq and coming back.

PMID- 16900918
TI  - Reshape the future.

PMID- 16900919
TI  - Optimizing epilepsy management in teenagers.
AB  - Optimal epilepsy management in teenage patients represents a particular
      challenge. These patients are often likely to respond more positively to a
      regimen that least disrupts their activities. In addition, as a patient group,
      they are more sensitive to peer perception. Current perceptions of older
      antiepilepsy drugs do not take into account frequent undesirable side effects or
      potential adverse interactions with other drugs. Furthermore, they often do not
      completely control seizures. Recent data suggest that not only do the newer
      antiepileptic drugs appear to be as efficacious as the older drugs, they also
      often have more favorable cognitive, cosmetic, and teratogenic side-effect
      profiles. In addition, newer antiepileptic drugs are being used more often in
      monotherapy. Successful management of epilepsy in teenagers requires that
      physicians not only understand the advantages that the newer antiepileptic drugs
      appear to provide but also consider the social impact of treatment on their
      patients.

PMID- 16900920
TI  - Characteristic brain magnetic resonance imaging (MRI) findings in neonates with
      tuberous sclerosis complex.
AB  - We describe the brain magnetic resonance imaging (MRI) findings in eight neonates
      with tuberous sclerosis complex to further delineate the spectrum of
      characteristic findings in these patients. In addition to the previously
      described characteristic brain MRI findings in neonates, which included cortical
      tuber, transmantle dysplasia, subependymal nodules, cerebral subependymal giant
      cell astrocytomas, white-matter anomalies, and hemimegalencephaly, we found one
      neonate with cerebellar subependymal giant cell astrocytomas and one patient who
      had a normal MRI and computed tomographic scan of the brain at 4 days of age but
      subsequently was found to have cortical tubers and subependymal nodules by MRI.

PMID- 16900921
TI  - Devic disease in a child with primary Sjogren syndrome.

PMID- 16900922
TI  - Diagnosing Sotos syndrome in the setting of global developmental delay and
      macrocephaly.
AB  - Sotos syndrome (cerebral gigantism) is characterized by macrocephaly, global
      developmental delay, characteristic facial dysmorphology, and a markedly advanced
      bone age. The purpose of this study was to describe the prevalence of Sotos
      syndrome in a consecutive series of patients with global developmental delay,
      which might modify our laboratory evaluation approach to this particular clinical
      situation. For a 10-year inclusive interval, the case records of all consecutive
      patients referred for global developmental delay in a single pediatric neurology
      practice were reviewed. Patients with macrocephaly were defined by an age- and
      gender-adjusted head circumference greater than or equal to the 98th percentile.
      Possible clinical factors associated with eventual diagnosis of Sotos syndrome in
      this group of macrocephalic children were tested with a two-tailed Fisher exact
      test. Of 261 children with global developmental delay, 18 (7%) had documented
      macrocephaly. Of these 18 children, 3 (17%) had an advanced bone age and were
      diagnosed with Sotos syndrome. In patients with global developmental delay and
      concomitant macrocephaly, Sotos syndrome is not uncommon. Assessment of bone age
      is a simple screening test for diagnosis of this entity and should be undertaken
      routinely in children with macrocephaly and global developmental delay even in
      the absence of other distinctive syndromic clinical features.

PMID- 16900923
TI  - Stanley S. Lamm, MD: A pioneer in child neurology.

PMID- 16900924
TI  - Walking with modafinil and its use in diplegic cerebral palsy: retrospective
      review.
AB  - A retrospective review of pediatric patients with spastic cerebral palsy was
      undertaken at Texas Tech University Health Sciences Center covering a period from
      January 1, 2000, until December 31, 2003. One hundred twenty pediatric patients
      were identified in the Texas Tech University Health Sciences Center child
      neurology clinic with spastic cerebral palsy. Fifty-nine patients of this group
      received modafinil treatment for cerebral palsy. Twenty-nine of the 59 patients
      were noted to have an improving gait on modafinil. Six of these modafinil-treated
      patients improved from no ambulation or only assisted ambulation to unassisted
      ambulation. This varied from taking a few steps without holding on to walking
      down the hall without assistance. Two patients with spastic diplegia secondary to
      prematurity have had a dramatic improvement in gait during the first 6 months
      after starting modafinil. Two other patients with spastic diplegia not included
      in this group of six patients taught themselves to stand up and walk while in
      water unassisted. During this same time period, only three non-modafinil-treated
      patients with mild cerebral palsy were noted with gait improvements, but not to
      the dramatic extent of the modafinil-treated group. A nonambulatory 5-year-old
      child, who presented for a requested wheelchair prescription because the mother
      had given up all hope of her child ever walking, is now taking independent steps
      unassisted after starting modafinil. Modafinil, a central nervous system
      stimulant, appears to improve tone and ambulation in spastic diplegic cerebral
      palsy.

PMID- 16900925
TI  - Ontogeny and physiology of the cavum septum pellucidum in premature infants.
AB  - We report the natural history of the closure of the cavum septum pellucidum in 47
      premature infants. In this study, a cavum septum pellucidum was present in all
      patients at 25 to 26 weeks' postconceptual age, in keeping with previous reports.
      The data from this study suggest that premature delivery does not change the
      natural history of the normal closure of the cavum septum pellucidum in most
      infants by 36 to 40 weeks' postconceptual age. Although not statistically
      significant, there is a suggestion from these data that higher grades of
      intraventricular hemorrhage are more frequently associated with loss (early
      closure) of the cavum septum pellucidum. One particularly illustrative case with
      a grade 4 intraventricular hemorrhage and subsequent hydrocephalus suggests that
      increases in pressure and volume in the lateral ventricles can cause the laminae
      of the septum pellucidum to approximate and appear to fuse earlier than expected.
      However, the fact that the cavum septum pellucidum reappeared in this case after
      ventricular pressure was decreased (postventricular shunt) suggests that
      approximation is not the sole factor in definitive fusion of the laminae of the
      septum pellucidum.

PMID- 16900926
TI  - Intractable intracranial tuberculous infection responsive to thalidomide: report
      of four cases.
AB  - Paradoxical enlargement and development of new intracranial tuberculomas and
      tuberculous brain abscesses on adequate antituberculosis treatment are well
      recognized and supposedly cytokine mediated. These lesions are often unresponsive
      to conventional antituberculosis treatment, corticosteroids, and surgery. We
      therefore assessed the effect of adjunctive thalidomide, a tumor necrosis factor
      alpha-modulating drug, in intractable intracranial tuberculosis that did not
      respond to standard medical and surgical therapy. Four consecutive children
      (three children with bacteriologic proof and one child with clinical evidence of
      intracranial tuberculosis) were studied. Three patients each had a giant
      tuberculous abscess, and the fourth had chronic basal arachnoiditis with
      progressive loss of vision. Three of the four patients had relentless neurologic
      deterioration, and all showed disease progression on neuroimaging despite full
      medical and appropriate surgical treatment. Marked clinical and neuroradiologic
      improvement occurred after thalidomide was added to the antituberculosis
      treatment regimen of these four patients. Adjunctive thalidomide might have a
      role in the management of intractable intracranial tuberculosis and needs further
      investigation in this regard.

PMID- 16900927
TI  - Short- and long-term outcome of severe neonatal nonhemolytic hyperbilirubinemia.
AB  - We studied the effects of hyperbilirubinemia on brainstem auditory pathways and
      neurodevelopmental status in 99 full-term neonates with severe nonhemolytic
      hyperbilirubinemia (total serum bilirubin level = 301 to 500 micromol/L) born
      between 1995 and 2000. These were divided into three groups: group 1, moderate
      hyperbilirubinemia (n = 30; mean maximum total serum bilirubin = 320.7 micromol/L
      or 18.9 mg%); group 2, severe hyperbilirubinemia (n = 63; mean maximum total
      serum bilirubin = 369.0 micromol/L or 21.7 mg%); and group 3, super
      hyperbilirubinemia (n = 6; mean maximum total serum bilirubin = 457.2 micromol/L
      or 26.9 mg%). All received phototherapy, and three neonates also had exchange
      transfusion. Initial brainstem auditory evoked potentials were recorded in all at
      the mean age of 3.1 months (range 1-9 months). At initial assessment, only nine
      neonates (9.1%) had abnormal brainstem auditory evoked potentials. All except two
      returned to normal at 2 years. These two children had a hearing threshold at 50
      nHL. We then compared serial brainstem auditory evoked potentials until 2 years
      for these nine cases with initial abnormal brainstem auditory evoked potentials,
      and nine cases with initial normal brainstem auditory evoked potentials were
      recruited for comparison. All 99 children had regular physical, neurologic,
      visual, and auditory assessments every 3 to 6 months until the age of 3 years.
      There was no significant correlation between demographic factors (gender,
      gestational age, or birthweight), maximum total serum bilirubin, and total serum
      bilirubin at discharge with an abnormal brainstem auditory evoked potential.
      There was no significant difference in the rate of brainstem auditory evoked
      potential abnormalities between the three groups: moderate (10%), severe (7.9%),
      and super (16.7%). All had normal neurodevelopmental status at 3 years. Only two
      children had transient mild motor delay and hypotonia, and both had normal
      brainstem auditory evoked potentials. There was no relationship between the
      abnormalities of the brainstem auditory evoked potentials and neurodevelopmental
      status. None of the three children receiving exchange transfusion had abnormal
      brainstem auditory evoked potentials or neurodevelopmental outcome. With the
      neurophysiologic and clinical outcomes in our cohort with severe nonhemolytic
      hyperbilirubinemia, we propose that the toxic effect of hyperbilirubinemia on
      auditory brainstem pathways might be transient provided that prompt treatment is
      initiated.

PMID- 16900928
TI  - Selenoprotein N muscular dystrophy: differential diagnosis for early-onset
      limited mobility of the spine.
AB  - Early spinal rigidity is a nonspecific feature reported in diseases such as
      neuromuscular and central movement disorders. We present a male patient with
      rigid spine muscular dystrophy caused by newly identified compound heterozygote
      mutations of the selenoprotein N gene and discuss this disease as a possible
      differential diagnosis for early-onset reduced spine mobility. Rigid spine
      muscular dystrophy is a rare myopathy presenting in childhood with a typical
      combination of stable or slowly progressive mild to moderate muscle weakness,
      limitation in flexion of the spine, and progressive restrictive ventilatory
      disorder. The clinical features of our patient include early-onset rigidity of
      his spine, scoliosis, mild muscular weakness predominantly of neck and trunk
      flexors, and restrictive ventilatory disorder. Biopsy of the biceps muscle
      revealed nonspecific myopathic changes, and molecular analysis confirmed the
      diagnosis of rigid spine muscular dystrophy. Thus, neuromuscular diseases such as
      muscular dystrophy must be considered in all patients presenting with early
      spinal rigidity, and genetic determination is a possible way to determine the
      diagnosis.

PMID- 16900929
TI  - Molar tooth sign in fetal brain magnetic resonance imaging leading to the
      prenatal diagnosis of Joubert syndrome and related disorders.
AB  - Joubert syndrome is a rare autosomal recessive disorder characterized by ataxia,
      developmental delay, and oculomotor and respiratory abnormalities in relation to
      cerebellar vermian and midbrain dysgenesis. The midbrain dysgenesis is
      responsible for the molar tooth sign on axial magnetic resonance imaging (MRI).
      This classic hallmark of Joubert syndrome has been identified in other disorders
      sharing overlapping clinical and radiologic features with Joubert syndrome.
      Recent identification of two different genes points to genetic heterogeneity in
      this group of disorders, now entitled Joubert syndrome and related disorders,
      making a genetic prenatal diagnosis not readily available. In addition, fetal
      ultrasonography lacks sensitivity in regard to posterior fossa malformation.
      Fetal MRI is now acknowledged as the method of choice to delineate posterior
      fossa malformation in a fetus. The identification of a molar tooth sign has,
      however, rarely been documented by a fetal brain MRI. We report a case of Joubert
      syndrome diagnosed prenatally using fetal MRI. We also discuss the etiology of
      Joubert syndrome in view of the recent genetic advances and murine models of
      cerebellar dysgenesis.

PMID- 16900930
TI  - Acquired alexia with agraphia syndrome in childhood.
AB  - The acquired alexia with agraphia syndrome is a conspicuous disorder of reading
      and writing in the absence of significant other language impairments that has
      mainly been recorded in adults. Pure cases are rare, with most patients
      displaying mild aphasic deficits. In children, acquired reading and writing
      disorders are generally reported as part of more encompassing aphasic syndromes
      affecting oral and written language equally, for example, Broca or Wernicke
      aphasia. Documented instances of predominant acquired reading and writing
      disorders in childhood are exceptional. We report an 11-year-old, right-handed
      boy who sustained a left temporoparieto-occipital hematoma following rupture of
      an arteriovenous malformation and who consecutively presented with the acquired
      alexia with agraphia syndrome associated with word-finding difficulties.
      Neuropsychologic and neurolinguistic data showed that there was no concomitant
      Gerstmann and/or angular gyrus syndrome. Th e recoveryfrom the anomia was quite
      favorable, but recovery of written language was more protracted and acted on the
      patient's further scholastic achievement. This case is reminiscent of a
      historical childhood case reported in 1939 and is consonant with adult cases in
      terms of lesion location and semiologic picture.

PMID- 16900931
TI  - Unusual phenotypic expression of an XLRS1 mutation in X-linked juvenile
      retinoschisis.
AB  - X-linked juvenile retinoschisis is a rare progressive vitreoretinal degenerative
      process that appears in early childhood, results in decreased visual acuity and
      blindness (if severe), and is caused by various mutations within the XLRS1 gene
      at Xp22.2. We report an affected family of Western European ancestry with X
      linked juvenile retinoschisis. The family was found to carry a 304C-->T
      substitution in exon 4 of the XLRS1 gene, resulting in an Arg102Trp amino acid
      substitution. Two of the four available clinical cases in this family were found
      to carry the mutation. All available mothers of affected males were found to be
      unaffected carriers of the mutation, a typical feature of X-linked diseases. Two
      new female carriers, sisters of affected males, were identified and counseled
      accordingly. Questionnaires on visual functioning were given to the affected
      family members to examine the psychologic and sociologic impact of X-linked
      juvenile retinoschisis, which documented an associated stigma even when affected
      with a "mild" phenotype.

PMID- 16900932
TI  - Severe form of Cockayne syndrome with varying clinical presentation and no
      photosensitivity in a family.
AB  - We report six patients with Cockayne syndrome type B without photosensitivity.
      The patients are from the same inbred family and exhibit variable clinical
      features. The main clinical manifestations were progressive encephalopathy
      including intracranial calcification and white-matter lesions, dwarfism without
      growth hormone deficiency, senile appearance, mental and motor retardation,
      atrophy of subcutaneous fat tissue, severe pectus carinatus, and spasticity.
      Clinical photosensitivity was not observed in any patient. Other clinical
      findings were cataract, pigmentary retinopathy, and peripheral neuropathy. The
      onset of the disease was between 3 and 6 months of age. Molecular genetic
      analyses in the family established linkage to ERCC6, the gene responsible for
      Cockayne syndrome type B, confirming the clinical diagnosis.

PMID- 16900933
TI  - Gillespie syndrome: two further cases.
AB  - We describe two unrelated male children with Gillespie syndrome, a rare genetic
      disorder consisting of cerebellar ataxia, partial aniridia, and psychomotor
      delay. One was more severely affected than the other, but neither had evidence of
      neuroregression. Partial aniridia was a key diagnostic marker, present at birth
      in both patients. Neurocognitive impairment and cerebellar ataxia were severe in
      one and mild in the other. The genetics of this condition remain undefined.
      Although believed to be an autosomal recessive condition, no clear, single
      candidate gene has been identified.

PMID- 16900934
TI  - Diplegia due to transcranial knife-blade injury in a 20-month-old child.
AB  - Transcranial stab wounds are uncommon among both adults and adolescents and
      rarely occur in children, particularly when caused by another child. A 20-month
      old girl was injured by a 3-year-old cousin, who introduced a knife blade into
      the brain through the left parietal region. The trajectory of the wound
      penetrated at least 5 cm, crossed the falx cerebri, and involved both motor
      cortical areas. The clinical sequela was a severe symmetric spastic diplegia.

PMID- 16900935
TI  - "A cold wind coming": Heinrich Gross and child euthanasia in Vienna.
AB  - Medicine in the German Third Reich became an instrument of Nazi political
      philosophy that included racial purification using biologic measures. This
      included an involuntary euthanasia program directed at mentally and physically
      disabled children. One such effort existed at the Am Spiegelgrund Hospital in
      Vienna under the direction of Dr Heinrich Gross. This article details the
      scientific and policy origins of child euthanasia in Vienna, the use of
      scientific materials obtained for personal and professional gain, and the postwar
      attempts to reconcile with this abject past.

PMID- 16900936
TI  - A half-century in clinical neurology.

PMID- 16900937
TI  - Can Asperger syndrome be diagnosed at 26 months old? A genetic high-risk single
      case study.
AB  - Asperger syndrome, a heritable condition entailing empathy deficits together with
      unusually narrow interests in individuals of normal or even above-average
      intelligence, was recognized only recently. Here we report the first-ever
      prospective study of a child born to two adults with a formal diagnosis of
      Asperger syndrome. The child's parents are both scientists (a mathematician and a
      chemist). The aim of study 1 was to test if the child also developed Asperger
      syndrome, given the heritability of the condition, and if Asperger syndrome can
      be detected at 26 months. At 18 months, the child was given the Checklist for
      Autism in Toddlers, and at 26 months, she was assessed diagnostically for autism
      spectrum conditions using the Autism Diagnostic Interview-Revised and the Autism
      Diagnostic Observational Scale. The child failed the Checklist for Autism in
      Toddlers at 18 months and met the criteria for Asperger syndrome at 26 months.
      This single case is consistent with the hypersystemizing, assortative mating
      theory of autism. This theory requires further testing with large samples. This
      study also demonstrates that Asperger syndrome can be diagnosed by age 26 months.
      The aim of study 2 was to test if dyadic eye contact in infancy is intact in a
      child later diagnosed with Asperger syndrome. The same child's eye contact was
      measured at three time points (3, 6, and 9 months) over her first year of life
      and compared with that of age-matched controls. Although the child had low rates
      of eye contact at 6 months, it was within the normal range at all three points in
      the first year of life. We conclude that low levels of eye contact are not
      predictive of later development of Asperger syndrome.

PMID- 16900938
TI  - Chorea induced by lamotrigine.

PMID- 16900939
TI  - Aripiprazole in childhood and adolescence for Tourette syndrome.

PMID- 16900940
TI  - Physical activity and body functionality: implications for obesity prevention and
      treatment.
AB  - Physical activity promotes metabolic adaptations that improve body functionality
      and contribute to the prevention of some diseases. With respect to energy and fat
      balance, physical activity facilitates the equilibrium between energy intake and
      expenditure as well as between fat intake and fat oxidation. When combined with a
      healthy diet that favors satiety with a reduced energy intake, exercise can
      induce a substantial mass loss in obese individuals. However, even the impact of
      an exemplary lifestyle does not seem to have the potential to decrease body mass
      in obese individuals down to the mass range of lean people. Up to now, we have
      not been able to induce mass changes exceeding 12%-15% initial body mass in obese
      male subjects under tolerable exercise and dietary habits, and this moderate
      success was accompanied by modifications in appetite and energy expenditure
      susceptible to compromise subsequent mass stability. As described in this paper,
      many environmental factors can influence energy balance and the ability to lose
      body fat in response to a healthy diet and (or) physical activity program.
      Particular attention is given to preliminary data obtained in our laboratory that
      suggest that knowledge-based work does not favor the same potential mass reducing
      effects as physical work. In fact, the acute effects of knowledge-based work
      suggest that this work modality may be rather susceptible to promote a more
      pronounced positive energy balance compared with what we may expect from a
      sedentary relaxing activity. This is problematic for obesity prevention in the
      future since knowledge-based work now represents the main working modality in a
      context of modernity.

PMID- 16900941
TI  - The modulatory effect of leptin on the overall insulin production in ex-vivo
      normal rat pancreas.
AB  - Leptin has a modulator effect on glucose-stimulated insulin secretion. To define
      the influences of different glucose (4, 8, 12, and 16 mmol/L) and leptin (5, 10,
      15, and 20 nmol/L) concentrations on total insulin release in ex vivo pancreatic
      preparations, a customized perfusion technique was used. Such a profile of
      concentration brought about an index for the combined effect of leptin and
      glucose on the production of insulin. Insulin output was measured by
      radioimmunoassay. Stimulated by glucose alone in the control group, insulin
      secretion confirmed a bi-phasic pattern. Addition of leptin in the experimental
      group suppressed insulin secretion compared with control. A U-shape pattern of
      suppression was observed when the leptin and stimulatory glucose concentrations
      were combined. At 12 mmol/L glucose, leptin showed maximal insulin suppression.
      Leptin's effect on insulin was glucose dependent and showed a reproducible U
      shaped pattern of suppression, which implicated possible direct dose-dependent
      interaction between leptin and glucose on insulin secretion.

PMID- 16900942
TI  - Epigallocatechin gallate preserves endothelial function by reducing the
      endogenous nitric oxide synthase inhibitor level.
AB  - Asymmetric dimethylarginine (ADMA), the endogenous nitric oxide synthase
      inhibitor, is thought to be a key factor contributing to endothelial dysfunction.
      Tea catechins can cause an endothelium-dependent vasorelaxation. The present
      study examined the effect of epigallocatechin gallate (EGCG), the major component
      of tea catechins, on endothelial dysfunction induced by native low density
      lipoprotein (LDL) in rats and oxidized LDL (ox-LDL) in cultured endothelial
      cells, and whether the protective effect of EGCG is related to reduction of ADMA
      level. A single injection of LDL (4 mg x kg(-1), i.v.) markedly reduced
      endothelium-dependent relaxation and the serum nitrite/nitrate (NO) level, and
      increased serum concentrations of ADMA, malondialdehyde (MDA), and tumor necrosis
      factor-alpha (TNF-alpha). EGCG (10 or 50 mg x kg(-1), i.p.) significantly
      attenuated the inhibition of vasodilator response to acetylcholine and the
      decreased serum nitrite/nitrate level, and reduced the elevated levels of ADMA,
      MDA, and TNF-alpha. Exposure of endothelial cells to ox-LDL (100 microg x mL(-1))
      for 24 h markedly increased the medium levels of lactate dehydrogenase (LDH),
      ADMA, TNF-alpha, and MDA, and decreased the level of nitrite/nitrate in the
      medium and the activity of dimethylarginine dimethylaminohydrolase (DDAH) in the
      endothelial cells. EGCG (10 and 100 microg x mL(-1)) significantly decreased the
      levels of LDH, ADMA, TNF-alpha, and MDA, and increased the level of
      nitrite/nitrate and the activity of DDAH. These results suggest that EGCG
      protects endothelial dysfunction induced by native LDL in vivo or by ox-LDL in
      endothelial cells, and the protective effect of EGCG on the endothelium is
      related to decrease in ADMA level via increasing of DDAH activity.

PMID- 16900943
TI  - The short-circuit current of the ileum, but not the colon, is altered in the
      streptozotocin diabetic rat.
AB  - Ion transport in control and streptozotocin-diabetic rat colon and ileum was
      studied using the Ussing chamber technique. No differences were observed between
      control and diabetic colonic mucosal short-circuit current under either basal or
      carbachol (100 nmol/L-1 micromol/L)-stimulated or prostaglandin E2 (100 nmol/L-1
      micromol/L)-stimulated conditions. Similarly to colonic tissues, no differences
      in the short circuit current in either carbachol-stimulated or prostaglandin E2
      stimulated tissues were observed between control and diabetic ileal mucosa. The
      basal diabetic ileal short circuit current (99.58 +/- 22.67 microA) was
      significantly greater than that of control ileal tissues (29.67 +/- 4.45 microA).
      This difference was abolished by the sodium-glucose-cotransporter inhibitor,
      phloridzin (50 micromol/L) (118.00 +/- 28.09 microA vs. 25.60 +/- 4.59 microA)
      and was also prevented by the replacement of glucose with mannitol in the buffer
      bathing the apical side of the tissue (control: 17.05 +/- 5.85 microA vs. 17.90
      +/- 3.10 microA). Acetazolamide (450 micromol/L; a carbonic anhydrase inhibitor),
      amiloride, and bumetanide (100 micromol/L each; Na+-channel blockers), piroxicam
      (50 micromol/L; a COX1 cyclooxygenase inhibitor), and ouabain (1 mmol/L; a K+
      transport inhibitor) had no effect on the basal short circuit current of either
      control or diabetic ileal tissues. This indicated that the alteration in the
      basal short circuit current of diabetic ileal tissues was due to a change in
      cellular glucose transport, whereas the evoked changes in short circuit current
      were unaffected by the diabetic state.

PMID- 16900944
TI  - Dual X-ray absorptiometry model for characterizing water in the human forearm
      using multiple frequency bioimpedance analysis.
AB  - The purpose of this study was to develop a method for measuring intracellular
      (ICW) and extracellular water (ECW) in the human forearm using multiple frequency
      bioimpedance analysis (MFBIA). The approach was (i) to measure whole-body and
      forearm fat-free mass using dual X-ray absorptiometry (DXA); (ii) to use these
      measurements to estimate the fat-free mass (FFM) resistivity in both the forearm
      and in the whole body; and (iii) to use the ratio of these FFM resistivities to
      estimate the resistivity in the ICW and ECW compartments of the forearm. To first
      demonstrate the accuracy of the DXA software in differentiating lean body mass
      from fat and bone within a volume of tissue, ex-vivo bovine muscle tissue samples
      (n = 3) were used to approximate the physical properties of the human forearm. It
      was found that although the human whole-body software overestimates FFM, it was
      slightly underestimated by the small animal software. Using this technique, DXA
      measures of FFM were obtained from human volunteers (n = 11; age = 20 +/- 5
      years; height = 170 +/- 12 cm; mass = 64 +/- 16 kg). These measures were used in
      conjunction with MFBIA measures of impedance of the whole body and of the forearm
      to determine the resistivities of the ICW and ECW compartments of the forearm,
      namely 375.8 +/- 25.2 ohms cm and 55.6 +/- 3.7 ohms cm, respectively. These were
      used in MFBIA equations to calculate the ICW, ECW, and total arm water (TAW)
      volumes of the human forearm. The calculated TAW and the ECW (+/- SD) volume
      fraction (667.29 +/- 200.15 mL and 0.169 +/- 0.039 mL, respectively) were in
      agreement with literature values. MFBIA results were compared with those obtained
      using nuclear magnetic resonance relaxometry (NMRR). MFBIA was performed on 15
      subjects before and after an intense maximal handgrip exercise to estimate
      changes in water volume in muscle. Following exercise, the total and
      intracellular water of the forearm increased on average by 8% +/- 3% and 10% +/-
      4% (mean +/- SD), respectively. In 5 healthy volunteers, MFBIA and NMRR were
      performed before and after a similar exercise of the forearm muscle. The changes
      with exercise of intracellular and total arm water volumes as measured by MFBIA
      were estimated. The percent increases in total water were found to be 9.4% +/-
      4.2% and 9.4% +/- 2.6% and in intracellular water were found to be 10.6% +/- 4.6%
      and 12.0% +/- 2.8% (mean +/- SD) for NMRR and MFBIA, respectively. The results
      show that the exercise-induced changes in ICW and TAW determined with the MFBIA
      model are consistent with those observed with NMRR and radiotracer literature.

PMID- 16900946
TI  - Cholecystokinin-2 receptors couple to cAMP-protein kinase A to depress excitatory
      synaptic currents in rat nucleus accumbens in vitro.
AB  - We recently reported that the activation of cholecystokinin-2 receptors depress
      evoked excitatory postsynaptic currents (EPSCs) in nucleus accumbens (NAc)
      indirectly through gamma-aminobutyric acid (GABA) acting on gamma-aminobutyric
      acid-B (GABA(B)) receptors. Here, we determined the second messenger system that
      couples cholecystokinin-2 receptors to the observed synaptic depression. Using in
      vitro forebrain slices of rats and whole-cell patch recording, we tested the
      hypothesis that cholecystokinin-2 receptors are coupled to cAMP and protein
      kinase A signaling pathway. Cholecystokinin-8S induced inward currents and
      depressed evoked EPSCs. Forskolin, an activator of adenylyl cyclase and rolipram
      that is an inhibitor of phosphodiesterase type IV, independently increased EPSC
      amplitude and blocked the inward current and synaptic depression induced by
      cholecystokinin-8S. Furthermore, the membrane-permeable cAMP analog, 8-bromo
      cAMP, blocked the cholecystokinin-8S effects. H89, a protein kinase A inhibitor,
      also blocked cholecystokinin-8S effects. However, depression of the evoked EPSC
      by baclofen, a GABA(B) receptor agonist, was not blocked by H89 or forskolin.
      These findings indicate that cholecystokinin-2, but not GABA(B), receptors are
      coupled to the adenylyl cyclase-cAMP-protein kinase A signaling pathway in the
      NAc to induce inward currents and cause synaptic depression.

PMID- 16900945
TI  - Preventive effects of cyclohexenonic long-chain fatty alcohol on diabetic
      cystopathy in the rat.
AB  - In this study, we investigated the preventive effect of n-hexacosanol on diabetes
      induced bladder dysfunction in the rat. Diabetes was induced in 8-week-old male
      Sprague-Dawley rats by administering an injection of streptozotocin (50 mg/kg,
      i.p.). The rats were randomly divided into 4 groups (age-matched control rats,
      diabetic rats without treatment with n-hexacosanol, and diabetic rats treated
      with n-hexacosanol (2 and 8 mg/kg, i.p. every day)) and maintained for 4 weeks.
      The serum glucose and serum insulin levels were determined, and the functions of
      bladder were estimated by voiding behavior, cystometric, and functional studies
      to carbachol and KCl. Furthermore, we examined possible diabetic induced
      histological changes in these rats. Treatment with n-hexacosanol did not alter
      diabetic status including body mass, bladder mass, and serum glucose and serum
      insulin levels, but significantly improved the maximum contraction pressure of
      the detrusor and residual urine volume in cystometric studies and Emax values to
      carbachol in functional studies in a dose-dependent manner. Diabetes induced
      bladder smooth muscle hypertrophy, which tended to be ameliorated by treatment
      with n-hexacosanol in a dose-dependent manner. Treatment with n-hexacosanol did
      not alter the diabetic status, but significantly improved diabetic cystopathy in
      a dose-dependent manner.

PMID- 16900947
TI  - Oxidative damage in the livers of senescence-accelerated mice: a gender-related
      response.
AB  - The prevalence of liver diseases emphasizes the need of animal models to research
      on the mechanism of disease pathogenesis. Furthermore, most of the liver
      pathologies have the oxidative stress as an important component. The senescence
      accelerated mouse strain SAMP8 was proposed as a valuable animal model for the
      study of liver diseases. To gain a better understanding of the mechanisms
      underlying degenerative processes in SAMP8 mice livers, we studied the oxidative
      induced damage in 5-month-old SAMP8 mice and SAMR1, senescence-accelerated
      resistant mice. We found profound differences in the antioxidant response to
      aging between sexes, with males displaying lowest levels of main antioxidant
      enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione reductase
      (GR) in SAMP8; whereas females had no difference in their activities, except for
      GR, when compared with their SAMR1 controls. The results obtained show the
      binomial SOD/CAT as an important factor for counteracting reactive oxygen species
      dependent damage. There were not pathological differences at the morphological
      level between both strains, although the decay in protection against free
      radicals had an immediate response by increasing lipid and protein oxidative
      damage in SAMP8 mice liver. At 5 months, both male and female SAMP8 mice confront
      the oxidative stress challenge to different extents. Indeed, proteins seem to be
      the most vulnerable biomolecule in SAMP8 male mice.

PMID- 16900948
TI  - Broad-spectrum sunscreens prevent the secretion of proinflammatory cytokines in
      human keratinocytes exposed to ultraviolet A and phototoxic lomefloxacin.
AB  - The combination of phototoxic drugs and ultraviolet (UV) radiation can trigger
      the release of proinflammatory cytokines. The present study measured the ability
      of sunscreens to prevent cytokine secretion in human keratinocytes following
      cotreatment of these cells with a known photoreactive drug and UVA. Keratinocytes
      were treated for 1 h with increasing concentrations of lomefloxacin (LOM) or
      norfloxacin (NOR), exposed to 15 J/cm2 UVA, and incubated for 24 h. NOR, owing to
      the absence of a fluorine atom in position 8, was non-phototoxic and used as a
      negative control. Cell viability and the release of 3 cytokines were assessed,
      namely interleukin-1alpha (IL-1alpha), interleukin-6 (IL-6), and tumour necrosis
      factor-alpha (TNF-alpha). The measurement of these cytokines may be a useful tool
      for detecting photoreactive compounds. To measure their ability to prevent
      cytokine secretion, various sunscreens were inserted between the UVA source and
      the cells. Treatment with NOR, NOR plus UVA, or LOM had no effect on the cells.
      LOM plus UVA, however, had an effect on cell viability and on cytokine secretion.
      IL-1alpha levels increased with LOM concentration. The release of TNF-alpha and
      IL-6 followed the same pattern at lower concentrations of LOM but peaked at 15
      micromol/L and decreased at higher concentrations. Sunscreens protected the cells
      from the effects of LOM plus UVA, as cell viability and levels of cytokines
      remained the same as in the control cells. In conclusion, the application of
      broad-spectrum sunscreen by individuals exposed to UVA radiation may prevent
      phototoxic reactions initiated by drugs such as LOM.

PMID- 16900949
TI  - Expression of protein kinase C isoforms in cardiac hypertrophy and heart failure
      due to volume overload.
AB  - The present study determined whether changes in the activity and isoforms of
      protein kinase C (PKC) are associated with cardiac hypertrophy and heart failure
      owing to volume overload induced by aortocaval shunt (AVS) in rats. A significant
      increase in Ca2+-dependent and Ca2+-independent PKC activities in the homogenate
      and particulate fractions, unlike the cystolic fraction, of the hypertrophied
      left ventricle (LV) were evident at 2 and 4 weeks after inducing the AVS. This
      increase coincided with increases in PKC-alpha and PKC-zeta contents at 2 week
      and increases in PKC-alpha, PKC-beta1, PKC-beta2, and PKC-zeta contents at 4
      weeks in the hypertrophied LV. By 8 and 16 weeks of AVS, PKC activity and content
      were unchanged in the failing LV. On the other hand, no increase in the PKC
      activity or isoform content in the hypertrophied right ventricle (RV) was
      observed during the 16 weeks of AVS. The content of G alpha q was increased in
      the LV at 2 weeks but then decreased at 16 weeks, whereas G alpha q content was
      increased in RV at 2 and 4 weeks. Our data suggest that an increase in PKC
      isoform content neither plays an important role during the development of cardiac
      hypertrophy nor participates in the phase leading to heart failure owing to
      volume overload.

PMID- 16900950
TI  - Effects of olive oil and its minor constituents on serum lipids, oxidative
      stress, and energy metabolism in cardiac muscle.
AB  - Recent lines of evidence suggest that the beneficial effects of olive oil are not
      only related to its high content of oleic acid, but also to the antioxidant
      potential of its polyphenols. The aim of this work was determine the effects of
      olive oil and its components, oleic acid and the polyphenol
      dihydroxyphenylethanol (DPE), on serum lipids, oxidative stress, and energy
      metabolism on cardiac tissue. Twenty four male Wistar rats, 200 g, were divided
      into the following 4 groups (n = 6): control (C), OO group that received extra
      virgin olive oil (7.5 mL/kg), OA group was treated with oleic acid (3.45 mL/kg),
      and the DPE group that received the polyphenol DPE (7.5 mg/kg). These components
      were administered by gavage over 30 days, twice a week. All animals were provided
      with food and water ad libitum. The results show that olive oil was more
      effective than its isolated components in improving lipid profile, elevating high
      density lipoprotein, and diminishing low-density lipoprotein cholesterol
      concentrations. Olive oil induced decreased antioxidant Mn-superoxide dismutase
      activity and diminished protein carbonyl concentration, indicating that olive oil
      may exert direct antioxidant effect on myocardium. DPE, considered as potential
      antioxidant, induced elevated aerobic metabolism, triacylglycerols, and lipid
      hydroperoxides concentrations in cardiac muscle, indicating that long-term intake
      of this polyphenol may induce its undesirable pro-oxidant activity on myocardium.

PMID- 16900951
TI  - Comparison of folic acid uptake characteristics by human placental
      choriocarcinoma cells at acidic and physiological pH.
AB  - The aim of this work was to characterize the placental uptake of folic acid from
      the maternal circulation. Using 2 human trophoblast cell lines (BeWo and JAR), we
      verified that uptake of 3H-folic acid was pH-dependent, increasing significantly
      with decreasing extracellular pH. In BeWo cells, uptake of 3H-folic acid at pH
      5.5 was (i) Na+-independent; (ii) inhibited by folic acid, 5
      methyltetrahydrofolate (5-MTHF), and methotrexate (MTX); (iii) inhibited by the
      anion transport inhibitors 4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid
      (DIDS) and 4-acetamido-4'-isothiocyano-2,2'-disulfonic acid stilbene (SITS); (iv)
      inhibited by the proton ionophore carbonyl cyanide 4
      (trifluoromethoxy)phenylhydrazone (FCCP); (v) not inhibited by blockers of
      receptor-mediated endocytosis (cytochalasin D and monensin); (vi) trans-inhibited
      by MTX and folic acid; and (vii) not affected by an anti-reduced folate
      transporter-1 (RFC) antibody. At pH 7.5, uptake of 3H-folic acid was (i) Na+
      independent; (ii) inhibited by folic acid and MTX, but not by 5-MTHF; (iii)
      inhibited by SITS, but not by DIDS; (iv) not affected by FCCP; (v) inhibited by
      monensin (but not by cytochalasin D); (vi) trans-inhibited by folic acid (but not
      by MTX); and (vii) inhibited by an anti-RFC antibody. In conclusion, in BeWo
      cells, both RFC and receptor-mediated endocytosis seem to be involved in 3H-folic
      acid uptake at pH 7.5, whereas at pH 5.5, RFC and (or) a low pH-operating
      transporter distinct from RFC are involved.

PMID- 16900952
TI  - Gender differences in the cardiac response to dietary conjugated linoleic acid
      isomers.
AB  - The present study was undertaken to assess the heart function, by the in vivo
      catheterization technique, of healthy male and female Sprague-Dawley rats fed
      different conjugated linoleic acid (CLA) isomers, (cis-9, trans-11 (c9,t11) and
      trans-10, cis-12 (t10,c12)) individually and in combination (50:50 mix as
      triglyceride or fatty acids) from 4 to 20 weeks of age. Whereas the triglyceride
      form of the CLA isomer mix lowered the heart rate, the rate of contraction
      (+dP/dt) and rate of relaxation (-dP/dt), systolic and diastolic pressures, mean
      arterial pressure, and the left ventricular systolic pressure were higher in male
      rats as compared with all the other dietary groups. In contrast, there were no
      significant effects in the cardiac function of the female rats in response to the
      CLA isomer mix in triglyceride form. Whereas the heart rate, +dP/dt, and left
      ventricular systolic pressure were lower in male rats fed the t10,c12 CLA isomer
      alone, the heart rate of the female rats was higher, but the systolic pressure,
      +dP/dt, and mean arterial pressure were lower compared with the control group.
      Also, the left ventricular end-diastolic pressure was specifically higher in the
      female rats in response to free fatty acids-containing CLA mix. Furthermore, an
      additive effect of the free fatty acids-containing CLA mix was seen in the +dP/dt
      and -dP/dt of female rats compared with the control group. These results indicate
      that CLA isomers exert differential effects on heart function and suggest the
      need for a complete evaluation of the benefits, interactions, and potential side
      effects of each isomer.

PMID- 16900953
TI  - Effects of low-calcium reperfusion and adenosine on diastolic behavior during the
      transitory systolic overshoot of the stunned myocardium in the rabbit.
AB  - The aims of the present study were to determine whether the transitory systolic
      overshoot (TSO) that occurs in the early reperfusion (R) of the stunned
      myocardium is accompanied by diastolic alterations, and to determine whether the
      R with low Ca2+ Krebs-Henseleit's solution or with adenosine modifies these
      alterations. Isolated-isovolumic rabbit hearts were divided in 3 groups (G). G1
      (n = 11) was perfused with Krebs-Henseleit's solution, subjected to 15 min of
      global ischemia and 30 min R; G2 (n = 10) was reperfused during the first 10 min
      with Krebs-Henseleit's solution [Ca2+] = 1 mmol/L, which was increased in the
      perfusate to 1.5 mmol/L up to 20 min R and at 2.5 mmol/L from 20 to 30 min R. G3
      (n = 12) was perfused with Krebs-Henseleit's solution with adenosine (0.03 microg
      x kg(-1) x min(-1)) from 10 min before ischemia and during all R. Left
      ventricular (LV) +dP/dtmax (mmHg/s), LV end diastolic pressure (LVEDP, mmHg), and
      1 relaxation index (t(1/2)) were measured in preischemic state, at 30, 50, 60,
      70, 90, and 120 s R, and then at 5 and 30 min R. The +dP/dtmax recovered to 621
      +/- 77 mmHg/s (p > 0.05), 346 +/- 31 mmHg/s (p < 0.05 vs. G1), and 533 +/- 76
      mmHg/s (p > 0.05) from preischemic value of 730 +/- 39, 690 +/- 32, and 758 +/-
      57 in G1, G2, and G3, respectively. The LVEDP in G1 and G3 increased early in the
      R, and it was negatively correlated with the +dP/dtmax (r = -0.63, p = 0.0369;
      and r = -0.71, p = 0.0090, respectively). The R with low Ca2+ abolished this
      correlation and attenuated the TSO phase. The correlation between LVEDP and
      +dP/dtmax in G1 and G3 and the lack of correlation in G2 suggests there are
      common mechanisms for the systolic and diastolic alterations during the TSO phase
      that are possibly related to Ca2+ overload but not with the vascular tone.

PMID- 16900955
TI  - What's in a Web site? Years into the Internet revolution, hospitals continue to
      struggle with their online presence.

PMID- 16900954
TI  - Anabolic responsiveness of skeletal muscles correlates with androgen receptor
      protein but not mRNA.
AB  - Anabolic effects of androgens on skeletal muscle are well documented, but the
      physiological and biochemical bases of these effects are poorly understood.
      Skeletal muscles that differ in their androgen responsiveness can be used to
      examine these mechanisms. We compared androgen receptor mRNA and protein levels
      of the rat levator ani, a perineal skeletal muscle that depends on androgens for
      its normal maintenance and function with that of the rat extensor digitorum
      longus, a limb muscle that does not require androgens. Western immunoblotting
      indicated that androgen receptor protein is significantly elevated in the levator
      ani relative to the extensor digitorum longus. Surprisingly, steady state
      androgen receptor mRNA levels were equivalent in these muscles, as determined by
      Northern blot analysis and quantitative RT-PCR. These results suggest that
      androgen responsiveness of skeletal muscles is determined by the level of
      androgen receptor protein in a particular muscle and that androgen receptor
      protein content is regulated by translational or post-translational mechanisms.

PMID- 16900956
TI  - Take a note. Many healthcare providers are adopting automated transcription
      technologies to save time.

PMID- 16900957
TI  - Automating the ED. Greater focus on emergency department efficiency has CIOs
      looking for new technologies.

PMID- 16900958
TI  - No clarity in NPI adoption. Confusion abounds as providers try and figure out the
      nuances of applying for national provider identifiers.

PMID- 16900959
TI  - Making it work. Vendor-provider partnerships can yield tremendous results. But,
      just like any relationship, success depends on effort from both sides.

PMID- 16900960
TI  - The 411 on CVE. Industry standards and common-language dictionaries are available
      to network security administrators, but is anyone paying attention?

PMID- 16900961
TI  - New paradigm for DM. Eric BOOK, M.D., Senior Vice President, Health Care
      Services, and Chief Medical Officer of Blue Shield of California, is writing a
      new script for disease management.

PMID- 16900962
TI  - Passport to the future. Interview by Anthony Guerra.

PMID- 16900964
TI  - Off-the-Chart success. A multi-specialty community healthcare practice implements
      an EHR system to improve patient care.

PMID- 16900963
TI  - Getting on schedule. With over 2,700 nurses, the University of Texas MD Anderson
      Cancer Center had to get a handle on scheduling.

PMID- 16900965
TI  - A case of life and death. New Hampshire has built a centralized repository where
      the state's funeral directors and healthcare workers can enter vital events
      information.

PMID- 16900966
TI  - Will we ever learn? A national healthcare identifier system may go a long way to
      reducing the danger of identity theft.

PMID- 16900967
TI  - Preparing for the worst. The real possibility that avian flu will hit the United
      States means all healthcare institutions need formal disaster recovery plans.

PMID- 16900969
TI  - The enemy is us. Institutions should look inward if frustrated by a lack of CPOE
      uptake in their facilities.

PMID- 16900968
TI  - Think big. By focusing too narrowly on EHR adoption, are we missing the point?

PMID- 16900970
TI  - Function over form. Multifunction devices can help speed the transition to
      electronic health records.

PMID- 16900971
TI  - In search of paperless workflow. MaternOhio partnered with KeyBank and Donnell
      Systems to develop a patient payment and medical records system.

PMID- 16900972
TI  - If at first you don't succeed ... old fashioned determination allowed the Harris
      County Hospital District to achieve automated-scheduling success.

PMID- 16900973
TI  - RHIO picks two for integration. Tallahassee, Fla.-based Big Bend RHIO has
      contracted with two local technology integration vendors to help link healthcare
      providers in the area.

PMID- 16900974
TI  - Not going it alone. Aurora Health Care looks to avoid headaches by outsourcing
      wireless support.

PMID- 16900975
TI  - A bitter pill.

PMID- 16900976
TI  - Brainpower fueled best by seafood.

PMID- 16900977
TI  - Dental fear and dealing with it.

PMID- 16900978
TI  - Find out what's behind that fuzzy-looking, black tongue.

PMID- 16900979
TI  - Milk helps build strong teeth and promotes oral health.
AB  - A great deal of research into the benefits of milk consumption has gone largely
      under the radar for many decades. There is a wealth of studies both in the United
      States and abroad to suggest that milk consumption is largely anti-cariogenic
      when combined with a typical routine of oral hygiene. This effect can be mostly
      attributed to several factors: tooth remineralization, inhibition of bacterial
      colonization, and biofilm inhibition. These abilities have been studied in detail
      and are likely due to numerous proteins found in milk. An attractive feature of
      milk from the community health perspective is its widespread consumption
      throughout the world. For this reason, studies have been initiated to investigate
      the possibilities of using milk to deliver fluoride and antibacterial antibodies
      to high-risk populations worldwide. This review will focus on the various
      components of milk, which promote oral health, and will also discuss common
      approaches to improve upon the oral health benefits of milk consumption.

PMID- 16900980
TI  - Managing caries in the 21st century: today's terminology to treat yesterday's
      disease.
AB  - BACKGROUND: For more than a century, dentistry has been treating the disease of
      dental caries largely by restoring teeth. Research in the microbiological and
      chemical mechanisms of the caries process over the past two decades suggests a
      fundamental rethinking of solely using this type of treatment approach. METHODS:
      A clinician's understanding of how the field has advanced has been impeded by the
      inconsistent use of dental terminology. This article will focus on defining
      dental caries and its related terms. CONCLUSIONS: The term "caries," although
      used very liberally in the field, should be further defined in its context of use
      to avoid confusion, until which time an accepted international terminology system
      is developed. PRACTICE IMPLICATIONS: Reducing or eliminating ambiguity in
      terminology used in managing dental caries is the first step in consistent
      diagnosis, detection, and finally treatment.

PMID- 16900981
TI  - Why an attorney cannot represent both sides of a practice sale.
AB  - This article is designed to point out select problems dentists may encounter when
      two or more dentists in a transaction seek to have the same attorney represent
      all of their interests.

PMID- 16900983
TI  - It's not your father's dentistry.

PMID- 16900982
TI  - Dental establishment business activity in California counties at the start of the
      millennium.
AB  - The Bureau of the Census reports for 2002 were used to develop business data for
      "average" dental establishments in each of the counties in California. On
      average, between 1997 and 2002, when compared to national information, the number
      of California statewide dental establishments increased at a greater rate, had a
      smaller resident population per establishment, reported lower gross receipts, had
      fewer employees, and paid lower salaries to employees.

PMID- 16900984
TI  - Dentists encouraged to consult reliable sources in potential influenza pandemic.

PMID- 16900985
TI  - Salivary diagnostics.

PMID- 16900986
TI  - A novel saliva test for caries risk assessment.
AB  - A new saliva test for caries risk assessment introduced in this study integrates
      a variety of host factors to predict for children, individual risk levels that
      are tooth-group specific. These various host factors correlate with caries
      history, DFT (decayed and filled teeth) or DFS (decayed and filled surfaces) in
      young adults. The test is based on the pattern of genetically determined
      oligosaccharides present on salivary glycoproteins. The mechanism behind the test
      is believed to be centered on the specific oligosaccharides that either
      facilitate bacterial attachment and colonization at the surface of teeth or
      protect against colonization by promoting agglutination and removal of free
      bacteria. It is the ratio of the two classes of oligosaccharides that is very
      strongly correlated with the numerical range of DFS or DFT observed in a young
      adult population.

PMID- 16900987
TI  - Oral-based techniques for the diagnosis of infectious diseases.
AB  - Saliva and other types of oral samples can readily be used for noninvasive
      diagnosis of diseases of the oral cavity and systemic diseases. Following an
      introduction outlining the types of oral samples and the analytes that can be
      measured in these samples, a detailed description of a novel oral-based
      diagnostic system to detect multiple bacterial and/or viral pathogens is
      presented. A reasonably priced, portable, point-of-care diagnostic system should
      be available within five years.

PMID- 16900988
TI  - Salivary diagnostics for oral cancer.
AB  - Oral cancers annually strike 38,000 individuals in the United States and hundreds
      of thousands of others around the globe. Despite treatment advances, the
      disease's overall five-year survival rate has not improved in the past three
      decades and remains among the worst of all cancers. One factor behind oral
      cancer's high mortality is the challenge detecting it at its early stages. The
      use of saliva for the detection of oral cancer has been a historical goal that
      has yet to come to fruition. This review highlights translational research
      efforts in alignment with initiatives sparked by the National Institute of Dental
      and Craniofacial Research toward bringing saliva diagnostics to fruition and, in
      particular, for saliva-based oral cancer detection.

PMID- 16900989
TI  - Oral fluid testing: new technology enables drug testing without embarrassment.
AB  - Drug abuse is a widespread problem across society, and its negative impact on
      performance and safety in the workplace cannot be overstated. Even as abuse of
      older, illicit drugs such as heroin, cocaine, marijuana, and amphetamines
      persists, new mind-altering chemicals continue to emerge, contributing to an ever
      changing landscape of drug abuse and its physical and psychological consequences.
      Abuse of multiple drugs, and the combined use of alcohol and illicit and
      prescription drugs, have become increasingly common. The growing and continually
      evolving problem of drug abuse demands novel strategies for drug testing that
      reliably and reproducibly detect drugs of abuse, offer an effective solution to
      persistent problems related to test accuracy and the potential for sample
      adulteration and substitution, and speak to the growing concerns over issues of
      individual privacy. Oral fluid testing is a reliable, new technology that
      overcomes many of the problems of older methods for drug detection.

PMID- 16900991
TI  - Snakes: the stuff of nightmaressssssss.

PMID- 16900990
TI  - Cultural, behavioral, social, and psychological perceptions of saliva: relevance
      to clinical diagnostics.
AB  - The search for a resource that can be used to detect a broad range of diseases
      easily and reliably is akin to a search for the diagnostic Holy Grail. Yet, each
      of us may have inside our mouths, a key to the pathological and disease biomarker
      library hidden inside our bodies. Saliva--the source of all this information--is
      the secretory product of glands located in or around the oral cavity. If one
      could read the stories of diagnostic information present within saliva, then the
      abundance of information waiting to be found could be comparable to a vast vault
      of information, such as the Internet. Upon dissection of this data, it would be
      seen that the source of this information is from saliva's origin as a filtrate of
      blood, and that the validity of both mediums should be equal. Although one day
      this may be the view, most people's hold of saliva, current and past cultures,
      have fared much more diverse meanings to the secretion. Ivan Pavlov's experiments
      has shown how closely tied salivation is with the thought of food, one of life's
      primary indulgences. The relationship between salivation and behaviors within our
      daily lives is undeniable. Yet most people never appreciate the uniqueness of
      saliva. Throughout the world, saliva carries definite positive and negative
      connotations, based upon its social, psychological, behavioral, and cultural
      settings. The thought of saliva may be viewed as grotesque in one population, yet
      may be the vehicle of blessing in other cultures. Saliva's double nature brings
      up some interesting cultural, social, behavioral, and psychological points about
      how saliva is perceived in the world, some of which are subsequently stated in
      order to present saliva as the spirited fluid it is.

PMID- 16900992
TI  - [Without risks and side effects? Product advertisements in dental journals].
AB  - We examined number, size, design, and scientific approach of advertisements
      published in three dental journals between 1970 and 2004. For this purpose, the
      Schweizer Monatsschrift fur Zahnmedizin (SMfZ), Zahnarztliche Mitteilungen (ZM;
      Ger many), and The Journal of the American Dental Association (JADA) were chosen.
      The January and July issues of each of the 35 volumes were analyzed. Of 28,711
      pages, 7265.5 were identified as advertisements (JADA: 29.9%, SMfZ: 24.8%, ZM:
      13.7%). While whole-page ads dominated in JADA (87.2%) and SMfZ (68.9%), ad-sizes
      were more balanced in ZM. During the observation period, the use of photographs
      increased, while that of drawings decreased. Images of products dominated as
      compared to pictures of the orofacial region. Citations from study results (SMfZ
      3.3%: ZM 2.5%; JADA 5.5%) and diagrams/tables (SMfZ: 3.2%; ZM: 1.0%; JADA: 4.5%)
      were rarely used, and an appreciable number of cited references could not be
      identified (SMfZ: 16%, ZM: 18%). More than 80% of the identifiable cited
      references corroborated the claim made in the advertisement. However, a critical
      attitude towards ads in dental journals appears justified.

PMID- 16900993
TI  - [Implant-supported bridges in the edentulous jaw. Clinical aspects of a simple
      treatment concept].
AB  - Clinical aspects of a simple treatment concept with fixed prostheses in the
      edentulous jaw are described. Fixed implant-supported reconstructions in the
      edentulous jaw require multiple implants, are technically complex, aesthetically
      demanding and metal-ceramic solutions are expensive. Specific surgical techniques
      to enhance the hard and soft tissue conditions become often necessary. Thus the
      bar-supported overdenture may be preferred, because problems with aesthetics and
      alveolar ridge deficiencies can be solved more easily and the number of implants
      is reduced. Both, the "All-on-Four" technique and the "Procera implant bridge"
      are simple type of fixed prostheses, comparable to overdentures or complete
      dentures with regard to design and technology. They present a cost-effective
      alternative, with predictable aesthetics and optimum passive fit.

PMID- 16900994
TI  - [Determination of prospective tooth positions by means of model analysis--the
      Staub Cranial System].
AB  - In modern reconstructive dentistry, practitioners delivering removable or fixed
      dentures still face problems when determining prospective tooth arch and tooth
      positions. Certain anatomical planes and reference lines, such as Camper's plane,
      interpupillary axis, etc. have been established as a guide. However, the ability
      and experience of the dentist remain essential. Adjusting the tooth arches is
      time-consuming and, therefore, expensive. To simplify and standardise the
      procedure, dental technicians and dentists may use the Staub Cranial System. It
      consists of three devices (Positionierer Ortho 1A, Einbaustativ Ortho 2A and
      Cranialstativ Ortho 3A) and the Staub Cranial software. With its aid, dental
      casts are surveyed and a penta-area is calculated. This penta-area, three
      dimensionally adjusted, may define exactly the site and position of the dental
      arch. In this article, the Staub Cranial System is presented and documented by a
      clinical case.

PMID- 16900995
TI  - Cytopathology of vertebral and paravertebral lesions.

PMID- 16900997
TI  - Cytologic features of pheochromocytoma and retroperitoneal paraganglioma: a
      morphologic and immunohistochemical study of 13 cases.
AB  - OBJECTIVE: To review the cytologic features and potential pitfalls of
      pheochromocytoma and retroperitoneal paraganglioma and to evaluate complications
      of the aspiration procedure and the diagnostic utility of immunocytochemistry.
      STUDY DESIGN: We reviewed 15 cytologic specimens from 12 patients with 13 tumors
      (1 bilateral case). Ten were adrenal (pheochromocytomas) and 3 extraadrenal
      paragangliomas. Eleven specimens were from fine needle aspiration (FNA)
      procedures that were performed in collaboration with radiologists using 23-25
      gauge needles. In 3 patients the cytologic material was obtained during
      intraoperative diagnosis. Immunocytochemistry was performed on alcohol-fixed
      smears. RESULTS: Two aspirates were hypocellular, while the remainder were
      cellular. Cells were distributed singly or formed discohesive groups. When
      present, cytoplasm was abundant and ill defined. Most cells had an eccentric
      nucleus and plasmacytoid morphology. Nuclear pleomorphism, binucleation and
      multinucletaion, naked nuclei and intranuclear preudoinclusions were common
      findings. In 2 cases a lipid background was seen focally. Evident cytoplasmic
      immunoexpression of synaptophysin or chromogranin was detected in the 10 cases
      analyzed. One patient developed a hypertensive episode during the FNA procedure.
      It was controlled medically without complications. CONCLUSION: When adequate
      cytologic material is present, the recognition of pheochromocytoma and
      extraadrenal paraganglioma is possible. Together with morphology,
      immunocytochemical studies allow a specific preoperative diagnosis. Scarce
      material can be a source of diagnostic errors. FNA of pheochromocytomas is not
      necessarily contraindicated. When analytic data are not diagnostic, FNA may
      follow. Aspiration must be performed in an area equipped with the therapeutic
      tools necessary to control a pheochromocytoma crisis.

PMID- 16900996
TI  - Fine needle aspiration biopsy of vertebral and paravertebral lesions:
      retrospective study of 124 cases.
AB  - OBJECTIVE: To evaluate the diagnostic value of image-guided fine needle
      aspiration biopsy (FNAB) in the diagnosis and management of vertebral and
      paravertebral lesions and to review similar studies in the literature. STUDY
      DESIGN: One hundred twenty-four FNAB cases (113 [corrected] patients) of
      vertebral and paravertebral lesions occurring over a 10-year period were
      retrieved from the archives of the University of Mississippi Medical Center for
      review and clinico-radiologic correlation. Thirty-four of the cases included a
      concurrent core needle biopsy sample, 15 cases had subsequent surgical specimens,
      while 32 cases had previously established malignancy. The age range was 11 days
      to 91 years (mean, 46 years), with 57 male patients and 56 female. RESULTS: One
      hundred five cases were vertebral lesions, and 19 cases were paravertebral
      lesions. FNAB diagnosis were malignant in 33.87% of cases, benign in 5.64%,
      suspicious in 4.03%, infectious/inflammatory and degenerative in 12.91%,
      unsatisfactory in 16.13% and negative in 27.42%. The overall sensitivity of the
      procedure was 89.3% and the specificity, 93.8%. The positive predictive value was
      95.7% and negative predictive value, 85.2%. CONCLUSION: FNAB is an effective
      means of establishing a definitive diagnosis of vertebral and paravertebral
      lesions, allowing appropriate patient management. Cell blocks, core biopsies and
      ancillary studies are useful adjuncts in rendering the diagnosis.

PMID- 16900998
TI  - Myeloid metaplasia in aspirates from enlarged spleens: a clue in the absence of
      peripheral blood findings characteristic of myelofibrosis.
AB  - OBJECTIVE: To assess the significance of finding myeloid metaplasia in splenic
      aspirates from patients presenting with mild to moderate firm splenomegaly, in
      the absence of characteristic peripheral blood findings, in diagnosing idiopathic
      myelofibrosis. STUDY DESIGN: Archival records pertaining to 14 patients diagnosed
      as having myeloid metaplasia on splenic aspirates performed between September
      2000 and April 2004 were analyzed. RESULTS: The relevant findings in these 9
      women and 5 men were: splenic enlargement 17-21 cm with homogeneous echotexture
      on ultrasonography, hemoglobin 4-10 g/dL, variable pattern of anemia, total
      leukocyte count 6,300-28,800/ mm3 with neutrophilia and a few late myeloid
      precursors on the differential count, normal platelet counts, dry bone marrow tap
      in 10 patients and cellular marrow aspirate with prominence of megakaryocytes
      dispersed in a maturing cell population of myeloid and erythroid series in 4
      patients. Splenic aspirates yielded foci of trilineage hematopoiesis suggestive
      of myeloid metaplasia, possibly due to myelofibrosis of idiopathic type, as
      confirmed on trephine biopsy in all cases. CONCLUSION: Splenic aspirates may be a
      useful tool for detecting myeloid metaplasia suggesting myelofibrosis when
      peripheral blood findings are not yet characteristic of the same. The procedure
      was not associated with any complications.

PMID- 16900999
TI  - Accuracy of aspiration cytology in thyroid cancer: a study in 1 institution.
AB  - OBJECTIVE: To evaluate sensitivity of fine needle aspiration cytology in
      diagnosing malignancy in histologically proven thyroid cancers. STUDY DESIGN: We
      analyzed the results of 335 smears from clinically significant and histologically
      proven primary thyroid cancers obtained from 9,115 aspirates, taking into account
      the pathologist's experience. RESULTS: The sensitivity for diagnosing thyroid
      malignancy in general was 88.0% (range, 82.6-97.2% from less to more experienced
      pathologist, respectively). It was higher for papillary (mean, 91.9%) and
      medullary (mean, 95.4%) carcinomas than for follicular cancer (mean, 50.0%).
      Biopsy showed thyroid cancer in 27.4% suspicious (range, 22.9-33.3%), 4.4%
      indeterminate (range, 1.9-6.6%) and 4.1% negative (range, 0-6.6%) smears.
      CONCLUSION: The more experienced the pathologist, the higher the sensitivity rate
      for recognizing thyroid cancer in general and by histologic type on aspirates
      despite some limitations of the method in identifying follicular carcinoma. We
      recommend thyroidectomy for patients with positive smears and follow-up for
      patients with benign, indeterminate and suspicious cytology, provided that the
      cytologic specimens were reviewed by an experienced pathologist.

PMID- 16901000
TI  - Cytomorphologic patterns in papillary cystic variant of acinic cell carcinoma of
      the salivary gland.
AB  - OBJECTIVE: To study the cytomorphologic profile of the papillary and cystic
      variant of acinic cell carcinoma (ACC-PCV) of the salivary glands. STUDY DESIGN:
      We studied 6 aspirates from 5 cases of ACC-PCV. RESULTS: All the cases had varied
      cytomorphologic features depending upon the degree of vacuolation of cells.
      However, common to all was a papillary pattern and a cystic fluid background with
      or without mucin blobs; that led to misdiagnosing the tumor as mucoepidermoid
      carcinoma on 2 occasions. The smears showed papillary fragments, sheets or
      clusters of vacuolated/histiocyte like cells and granular cells. The
      histiocytelike cells resembled macrophages, with finely vacuolated cytoplasm and
      an eccentrically placed nucleus with frequent binucleation. Vascular cores were
      seen in a few aspirates. The granular cells were similar to those seen in the
      usual acinic cell carcinoma but were smaller. The tumor did not show any acinar
      pattern and lacked naked nuclei in the background. In 4 aspirates finely
      distributed, brown hemosiderin pigment was detected in the vacuolated cells.
      CONCLUSION: ACC-PCV is papillary and cystic and hence is often not recognized as
      acinic cell carcinoma. However, papillary fragments of vacuolated cells or
      histiocytelike cells and granular cells are clues to the diagnosis.

PMID- 16901001
TI  - Nucleic acid amplification of Mycobacterium tuberculosis complex DNA from
      archival fine needle aspiration smear scrapings vs. fresh fine needle aspirates
      of tuberculous lymphadenitis.
AB  - OBJECTIVE: To assess the efficacy of the nucleic acid amplification (NAA)
      technique for Mycobacterium tuberculosis (MTB) complex from archival fine needle
      aspirate (FNA) smear scrapings of confirmed cases of extrapulmonary tuberculosis
      (EPTB) for a retrospective diagnosis of EPTB as compared to NAA from fresh FNA
      material from the same cases. STUDY DESIGN: Smear scrapings from 51 cases; 33
      cases of tuberculous lymphadenitis (from patients who had undergone NAA 1 year
      before for MTB from fresh FNA material); 13 negative controls from
      nontuberculous, archival FNA smears; and 5 known acid-fast bacilli (AFB)-positive
      sputum smears, were subjected to NAA using the IS6110 primer sequence of M
      tuberculosis. Ziehl-Neelsen staining was done in all the smears. RESULTS: Of the
      33 cases of tuberculous lymphadenitis, 15 (45.4%) were AFB positive and 18
      (64.5%) AFB negative. MTB NAA was positive in 73.3% (11 of 15 AFB-positive cases)
      in the freshly aspirated material and was observed in 60% (9 of 15 AFB-positive
      cases) when done on DNA extracted from the archival smear scrapings of the same
      cases. Similarly, in the 18 AFB-negative cases, MTB NAA positivity was 72.2% (13
      of 18) on fresh material and 44.4% (8 of 18) on archival smear scrapings from the
      same AFB-negative cases. Overall NAA positivity was 51.5% for archival smear
      scrapings as compared to 71% for fresh FNA of the same cases. CONCLUSION: Low NAA
      sensitivity of MTB DNA in archival material of known tuberculous cases limits the
      routine use of NAA based retrospective molecular diagnosis of MTB complex.

PMID- 16901002
TI  - Evaluation of Papanicolaou stain for studying micronuclei in buccal cells under
      field conditions.
AB  - OBJECTIVE: To compare Papanicolaou (Pap) and May-Grunwald Giemsa (MGG) stain as 2
      techniques for staining for buccal mucosal cells to detect micronuclei (MN)
      infield studies. STUDY DESIGN: Eighty cytologic smears (2 per individual) were
      taken from the buccal mucosa of 40 cigarette smokers recruited at a rural village
      in Egypt. Forty smears were stained with Pap stain and 40 with MGG stain. All
      were assessed for cellularity and scored for MN. RESULTS: Pap stain was faster
      and easier to process and transport in the field study than was MGG stain.
      Regarding MGG smears, bacteria and cell debris masked the MN as compared to Pap
      smears, in which the fixative destroyed the bacteria and made the cell boundaries
      clearly demarcated. Using Pap stain, MN were seen easily in transparent
      cytoplasm. CONCLUSION: Pap stain is the preferred method infield studies for
      scoring and detecting MN in cells of buccal mucosa.

PMID- 16901003
TI  - Leishman-Giemsa cocktail: an effective Romanowsky stain for air-dried cytologic
      smears.
AB  - OBJECTIVE: To develop an economical, quick, readily available and simple
      alternative to May-Grunwald-Giemsa (MGG) stain and so to explore the combination
      of Leishman and Giemsa stain (LG cocktail). STUDY DESIGN: One wet-fixed and 2 air
      dried smears were prepared from 720 cases during the period January 2003-November
      2004. The LG cocktail and MGG stain were used on the air-dried smears and
      Papanicolaou stain in wet-fixed smears. Diagnoses of the cases were made using
      the LG cocktail-stained smears, and then its diagnostic efficacy was cross
      checked with the MGG- and Papanicolaou-stained smears by the same
      cytopathologist. A comparative study of the LG cocktail and MGG-stained smears
      was done. RESULTS: The results achieved with the LG cocktail-stained smears were
      comparable to or even better than those with the MGG-stained smears, with
      excellent diagnostic efficacy. CONCLUSION: As compared to MGG stain, the 1-step
      LG cocktail is cheaper, easier to standardize and quicker.

PMID- 16901004
TI  - Diagnostic accuracy of toluidine blue-stained wet films in effusion cytology.
AB  - OBJECTIVE: To evaluate the usefulness of toluidine blue-stained wet films in the
      preliminary cytologic evaluation of serous effusions by means of specificity,
      sensitivity, and positive and negative predictive value. STUDY DESIGN: One
      hundred seventy-six samples consisting of 122 pleural and pericardial effusions
      and 54 peritoneal effusions from 160 patients were included in the study. A
      toluidine blue-stained wet film of each sample was evaluated, and diagnoses were
      compared with the diagnoses by conventional smears and cell blocks on the same
      sample. RESULTS: The sensitivity of wet films was 69%, 68% in pleural and
      pericardial effusions and peritoneal effusions, respectively, and the specificity
      of wet films was 93%, 92% in pleural and pericardial effusions and peritoneal
      effusions, respectively. Positive predictive values of smears alone were 78% and
      75%; negative predictive values of smears alone were 96% and 95% in pleural and
      pericardial effusions and peritoneal effusions, respectively. CONCLUSION:
      Preliminary cytologic evaluation of serous effusions with toluidine blue-stained
      wet films is simple and economical. It provides the opportunity to plan
      additional procedures for the samples.

PMID- 16901005
TI  - Shift in vaginal flora (bacterial vaginosis) and the frequency of
      chorioamnionitis in a high-risk population.
AB  - OBJECTIVE: To test the association between a shift in vaginal flora (SVF) and
      chorioamnionitis in a population with a high prevalence of both conditions. STUDY
      DESIGN: Subjects were women with Pap smears and placentas examined at the Medical
      Center of Louisiana, New Orleans. The presence of subchorionitis, chorionitis,
      chorioamnionitis and necrotizing chorioamnionitis was evaluated blindly on
      placental tissue sections. The presence of SVF was evaluated on matching cervical
      Pap smears obtained during gestation. RESULTS: Three hundred twenty-two placentas
      and the corresponding Pap smears were examined. Chorioamnionitis was identified
      in 112 placentas. It was not significantly associated with maternal age or
      ethnicity, but its prevalence was inversely related to gestational age. SVF was
      observed in 114 Pap smears. It was more common among African Americans than other
      ethnic groups but was not significantly associated with maternal age or
      gestational age at delivery. SVF was more often observed in Pap smears collected
      in early pregnancies than in those collected later. There was no significant
      association between chorioamnionitis and SVF before and after accounting for
      ethnicity, maternal age, gestational age at Pap smear collection, and interval
      between Pap smear collection and delivery. CONCLUSION: SVF had no significant
      predictive value for chorioamnionitis in our study population.

PMID- 16901006
TI  - The post-LLETZ cervical smear: influence of time interval from LLETZ.
AB  - OBJECTIVE: To determine the effect of the time interval between large loop
      excision through the transformation zone (LLETZ) and the first subsequent
      cervical smear on the adequacy of the smear for cytologic interpretation and
      cytologic abnormality rates. STUDY DESIGN: A retrospective, case-note analysis of
      women attending a colposcopy clinic between May 1, 1999, and March 31, 2002, who
      had high grade histologic lesions on their LLETZ biopsy, irrespective of the
      referral indication. RESULTS: A total of 771 women were included in the study.
      Negative smears were reported in 639 (82.9%); 82 (10.6%) were abnormal and 50
      (6.5%) unsatisfactory. The post-LLETZ smear was performed at a median interval of
      105 days (range, 48-829). A univariate logistic regression analysis did not
      reveal any relationship between the rate of unsatisfactory or abnormal smears and
      the interval since having LLETZ (p = 0.935). CONCLUSION: These data do not
      support the traditionally held concept that performing the post-LLETZ smear
      before 6 months increases the rate of unsatisfactory or abnormal smears.

PMID- 16901007
TI  - Glassy cell carcinoma of the cervix: cytologic features and expression of
      estrogen receptor, progesterone receptor and Her2/neu protein.
AB  - OBJECTIVE: To analyze the cytologic features, estrogen and progesterone
      receptors, and Her2/neu protein in glassy cell carcinoma (GCC) of the cervix.
      STUDY DESIGN: Cases were analyzed using various parameters, including age at
      presentation, stage, treatment and clinical course. Between 1990 and 2003,
      patients with primary cervical carcinomas were treated and cytopathologic
      analyses performed. Tests for estrogen receptor (ER), progesterone receptor (PR)
      and Her2/neu protein were performed on paraffin sections. RESULTS: GCC of the
      cervix is composed of large cells with abundant chromatin, which gives them their
      characteristic glassy appearance. Eleven cases were identified as GCC. One case
      (9.1%) was correctly diagnosed from the cervicovaginal smear. Among the GCC
      cases, ER, PR and Her2/neu were positive in 2 (18.1%), 1 (9.1%) and 5 (45.4%)
      cases, respectively. CONCLUSION: Cytology of GCC reveals characteristic features
      that differ from those of other carcinomas of the cervix. GCC has unique
      cytologic characteristics and causes diagnostic confusion, possibly leading to
      incorrect diagnoses. The reason for such low diagnostic precision in cytology
      might be due to the lack of differentiation and low frequency of this tumor. Our
      results, demonstrating Her2/ neu overexpression, may correlate with more
      aggressive behavior and a worse clinical outcome.

PMID- 16901009
TI  - Nasal cytobrush cytology: evaluation of the hyperchromatic supranuclear stria.
AB  - OBJECTIVE: To evaluate the hyperchromatic supranuclear stria (SNS) in various
      types of rhinopathies. STUDY DESIGN: The study included 42 patients with
      rhinopathies and a control group consisting of 28 healthy adults. The rhinopathy
      group was categorized into 4 subgroups, including allergic rhinitis, infective
      rhinitis, vasomotor rhinitis and mixed group. Cytologic samples were obtained by
      cytobrush from the middle one third of the inferior turbinate. RESULTS: The
      hyperchromatic SNS was present in the majority of ciliated cells in a high
      percentage in the control group (91.7%), whereas in the pathologic group it was
      40%. The difference is significant (p = 0.0000). CONCLUSION: Nasal cytology is a
      simple, reliable tool for the diagnosis of rhinopathies.

PMID- 16901008
TI  - Clinicopathologic roles of tumor-infiltrating lymphocytes and CD8-positive
      lymphocytes in lung cancer imprint smears in squamous cell carcinoma and
      adenocarcinoma.
AB  - OBJECTIVE: To investigate the presence of tumor-infiltrating lymphocytes (TILs)
      and CD8-positive lymphocytes (CD8s) in lung cancers and to examine the prognostic
      significance of their relationship with clinicopathologic parameters. STUDY
      DESIGN: Primary tumor imprint smears from 83 lung cancers were consecutively
      obtained at surgery at Tsuchiura Kyodo General Hospital between 1996 and 1998.
      TILs were observed in Papanicolaou-stained smears, and CD8s were
      immunocytochemically visualized. RESULTS: TILs were judged positive in 42 cases
      (51%), and 34 of 83 cases (41%) were positive for CD8s. There was no correlation
      between the frequency of TILs and CD8s. TILs assessed by Papanicolaou staining in
      83 cases showed no correlation with any clinicopathologic factors. CD8s were
      observed more frequently in squamous cell carcinomas (SCCs) than other
      adenocarcinomas. A high frequency of CD8s was associated with lymph node
      metastasis (p = 0.043), stage (p = 0.025) and tumor differentiation (p = 0.03).
      TILs and CD8s made no significant difference in survival. However, in SCC the
      patients positive for TILs but negative for CD8s survived and had a significantly
      better prognosis than did the others (p = 0.037). CONCLUSION: CD8s were
      associated with tumor progression and development of malignancy in lung cancers.
      Especially in SCC, the cases had a high frequency of TILs. A low number of CD8s
      may correlate with a favorable prognosis.

PMID- 16901010
TI  - Cytologic analysis of alterations induced by Smoking and by alcohol consumption.
AB  - OBJECTIVE: To analyze cytologically the buccal mucosa of smoking and nonsmoking
      volunteers to determine what cellular changes are induced by cigarettes and
      alcohol consumption. STUDY DESIGN: In order to evaluate cellular changes induced
      by smoking and alcohol consumption, exfoliative cytology was used for the
      analysis of mucosal smears obtained from the buccal mucosa of 25 smokers and 25
      nonsmokers. The number of cigarettes consumed, duration of smoking, presence or
      absence of alcohol ingestion, ingested alcohol dose and frequency of consumption,
      and most frequently used type of alcoholic beverage were determined using a
      questionnaire. Three smears from each individual stained by the Papanicolaou
      method were analyzed quantitatively and qualitatively under a light microscope by
      2 experienced examiners in terms of inflammatory and dysplastic alterations and
      of the degree of epithelial maturation. RESULTS: Although numerous alterations
      were observed in smokers they corresponded up to only Papanicolaou class II and
      were not significantly different from nonsmokers (Mann-Whitney and chi2 tests, p
      < 0.05). A higher proportion of inflammatory cells (polymorphonuclear and
      mononuclear cells) were obtained from smokers as compared to nonsmokers, while
      the proportion of bacteria was similar in the 2 groups. CONCLUSION: The findings
      indicate that even after a short period of cigarette use and alcohol consumption,
      inflammatory alterations were detectable on exfoliative cytology of the buccal
      mucosa in a young group, demonstrating the usefulness of cytology for early
      detection in smokers.

PMID- 16901011
TI  - Rapid staining with the modified Gill-Shorr method for reliable, rapid
      bronchoscopic diagnosis.

PMID- 16901012
TI  - Crush cytology of pleomorphic xanthoastrocytoma.

PMID- 16901013
TI  - Fine needle aspiration biopsy in central giant cell lesion: a report of 3 cases.
AB  - BACKGROUND: Fine needle aspiration biopsy (FNAB) is a safe and efficient
      diagnostic method used in numerous lesions of the head and neck region. However,
      its use in central giant cell lesion (CGCL) is rarely seen. CASES: Three cases of
      CGCL were initially diagnosed with FNAB, emphasizing the cytologic and
      immunocytochemical features. CONCLUSION: FNAB, particularly when associated with
      clinical, radiographic and laboratory examinations, plays an important role in
      the preliminary diagnosis of CGCL.

PMID- 16901014
TI  - Pulmonary epithelioid hemangioendothelioma: report of a case with fine needle
      aspiration biopsy.
AB  - BACKGROUND: Pulmonary epithelioid hemangioendothelioma (PEH) is a rare, low
      grade, malignant vascular tumor that typically presents with multiple pulmonary
      nodules in young women. This report details the cytopathologic and pathologic
      findings in an unusual case presenting in an older male with a pleural effusion,
      dominant nodule and multiple bilateral infiltrates. CASE: A 62-year-old, male
      nonsmoker was referred due to increasing dyspnea. Chest radiography revealed a
      pleural effusion and nodular infiltrate in the right upper lobe of the bronchus.
      Thoracocentesis and thoracoscopy were performed, with a pleural drain inserted.
      Bronchoscopy revealed a right upper lobe bronchus occluded by a greyish, necrotic
      mass. Various cytopathologic sampling techniques, including fine needle
      aspiration biopsy, as well as traditional histopathologic biopsies were
      performed. Cytologic specimens showed loosely cohesive, epithelioid cells that
      were binucleated and multinucleated. Chromatin was granular, with scattered,
      small, multiple nucleoli with occasional, variably sized cytoplasmic vacuoles.
      The patient's condition deteriorated, and he died 3 weeks after admission.
      CONCLUSION: Pulmonary epithelioid hemangioendotheliomas are unusual neoplasms
      with a epithelioid, discohesive cellular appearance. It can mimic other, more
      commonly seen pulmonary neoplasms. Careful attention to cytomorphologic features
      and application of ancillary studies assist in making the diagnosis.

PMID- 16901015
TI  - Diagnostic cytologic features of an epididymal melanotic neuroectodermal tumor of
      infancy present in scrotal fluid: a case report.
AB  - BACKGROUND: The cytologic features of melanotic neuroectodermal tumor of infancy
      (MNTI) have been described in rare cases only, and these reports have been based
      solely on direct smears obtained from aspirated tumor material or from touch
      preparations of resected tumors. CASE: We report, to our knowledge, the first
      documented case of an epididymal MNTI diagnosed from aspirated hydrocele fluid
      processed using the ThinPrep system (Cytyc Corp., Boxborough, Massachusetts,
      U.S.A.). CONCLUSION: Based on a 15 year retrospective review of scrotal fluids
      submitted for cytologic evaluation to our laboratory, MNTI represented the sole
      neoplasm that was represented in the fluid and could be specifically diagnosed.
      Compared to the direct smear evaluation in our case and other published reports,
      the ThinPrep method enables the recognition of both neuroblast-like cells and
      larger melanin-containing epithelial cells in scrotal fluid, thereby aiding in
      the specific diagnosis of MNTI and minimizing the risk of misdiagnosing this
      tumor as a more aggressive neoplasm.

PMID- 16901016
TI  - Preoperative diagnosis of renal angiomyolipoma with fine needle aspiration
      cytology: a report of 3 cases.
AB  - BACKGROUND: Angiomyolipoma is a rare benign neoplasm, commonly involving the
      kidney. Preoperative diagnosis on fine needle aspiration cytology can confirm the
      diagnosis, reducing the chances of unnecessary surgery. CASES: We studied cases
      of renal angiomyolipoma (AML) presenting within 1 year with palpable renal masses
      confirmed on ultrasound to be of renal origin. Fine needle aspiration cytology
      (FNAC) smears showed a few cohesive syncytial fragments with adipocytes, spindle
      cells and isolated single cells with foamy cytoplasm; a diagnosis of AML was
      made. The diagnosis was confirmed on histopathology, which showed mature adipose
      tissue, tortuous and thick-walled blood vessels lacking elastic tissue lamina and
      bundles of smooth muscles that seemed to emanate from the blood vessels.
      CONCLUSION: A preoperative diagnosis of renal AML is of great importance for
      correct management. In fact, when the lesion is small and asymptomatic, a
      conservative approach may be considered. Partial nephrectomy is possible with
      masses < 5 cm. Preoperative FNAC along with computed tomographic findings and
      immunocytochemical analysis of FNAC smears with HNB-45 can confirm the diagnosis
      of AML, thus preventing unindicated nephrectomy.

PMID- 16901018
TI  - Pseudomelanosis of the bladder: a case report.
AB  - BACKGROUND: Pseudomelanosis is due to deposition of pseudomelanin and is best
      known as the entity pseudomelanosis coli. However, pseudomelanosis in the urinary
      tract has never been described. Pigmentation of the urothelium, known as
      melanosis vesica, is characterized by deposition of melanin pigment granules
      without signs of atypia. Simple (true) melanosis of the bladder is uncommon.
      CASE: A 52-year-old man presented with macroscopic hematuria. Cystoscopy and
      microscopic evaluation revealed pigmentation of the bladder urothelium diagnosed
      as pseudomelanosis vesica due to deposits of melaninlike pigment in the absence
      of detectable melanocytes and detectable by urine cytology. CONCLUSION:
      Pseudomelanosis vesica is a benign lesion that has never before been observed in
      the urinary tract.

PMID- 16901017
TI  - Fine needle aspiration cytology of a metastatic duct carcinoma of the prostate: a
      case report.
AB  - BACKGROUND: Prostatic ductal carcinoma (PDC) is a rare variant of prostatic
      adenocarcinoma. Without proper clinical information, a fine needle aspiration
      (FNA) diagnosis of metastatic PDC can be challenging as this tumor can
      morphologically mimic adenocarcinomas from other sites. To our knowledge, FNA
      findings of metastatic PDC have not been previously reported. CASE: An 85-year
      old man presented with a large, destructive pelvic bone lesion with soft tissue
      extension. He had undergone a prostatectomy 30 years earlier for "benign
      prostatic hypertrophy" but had no known history of malignancy. The aspirates were
      hypercellular and composed of numerous monolayered or folded cohesive sheets of
      tumor cells with minimal cytologic atypia. The tumor cells had abundant, clear
      cytoplasm, evenly spaced nuclei, finely granular chromatin, inconspicuous
      nucleoli and occasional mitotic figures. The background was clean and contained a
      few wisps of thin mucin. Cell block sections revealed tumor cells forming
      tubulopapillary architecture lined with tall columnar cells with focal nuclear
      pseudostratification, reminiscent of uterine endometrial carcinoma. Positive
      immunoreactivity for prostate-specific antigen and prostatic acid phosphatase
      confirmed the tumor's prostatic origin. CONCLUSION: Because of the rarity and
      nonspecific cytomorphologic characteristics of this tumor, clinical history,
      radiologic findings and a high index of suspicion in conjunction with ancillary
      studies are important in achieving a correct FNA diagnosis of metastatic PDC.

PMID- 16901019
TI  - Eccrine porocarcinoma: Report of a case with fine needle aspiration cytology,
      histopathology and immunohistochemistry.
AB  - BACKGROUND: Although relatively rare, eccrine porocarcinoma (EP) is widely
      recognized in the literature as the most common of the sweat gland adenocarcinoma
      types. EP is an adenocarcinoma of the eccrine sweat gland with a propensity to
      recur locally and metastasize to regional lymph nodes. This paper presents the
      second case of fine needle aspiration (FNA) cytology of an EP along with
      histopathology and immunohistochemistry. CASE: A 64-year-old Filipino woman had a
      history of EP of the right eyebrow and presented with a right preauricular mass.
      The cytopathologic features of the case included: (1) clusters and sheets of
      polyhedral epithelial tumor cells with abundant, cyanophilic, vacuolated
      cytoplasm; round to oval, hyperchromatic nuclei; and occasional prominent
      nucleoli; (2) multinucleated tumor cells; (3) singly dispersed and relatively
      large aggregates of parakeratotic squamous cells; and (4) a background of
      necrotic debris. CONCLUSION: EP is crucial to developing an effective (curative)
      surgical plan. FNA cytology potentially provides a convenient, safe and effective
      approach to solving a challenging differential diagnosis. The constellation of
      cytologic findings probably is distinctive and, in the proper clinical setting,
      may be diagnostic. History is important in making an accurate diagnosis.

PMID- 16901020
TI  - Erythromelalgia: an underrecognized manifestation of small-fiber neuropathy.

PMID- 16901021
TI  - John J. R. Macleod--Nobel prize for discovery of insulin.

PMID- 16901022
TI  - A new look at osteoporosis outcomes: the influence of treatment, compliance,
      persistence, and adherence.

PMID- 16901023
TI  - Adherence to bisphosphonate therapy and fracture rates in osteoporotic women:
      relationship to vertebral and nonvertebral fractures from 2 US claims databases.
AB  - OBJECTIVE: To characterize the relationships between adherence (complance and
      persistence) to bisphosphonate therapy and risk of specific fracture types in
      postmenopausal women. PATIENTS AND METHODS: Data were collected from 45 employers
      and 100 health plans in the continental United States from 2 claims databases
      during a 5-year period (January 1, 1999, through December 31, 2003). Claims from
      patients receiving a bisphosphonate prescription (alendronate or risedronate)
      were evaluated for 6 months before the Index prescription and during 24 months of
      follow-up to determine total, vertebral, and nonvertebral osteoporotic fractures,
      persistence (no gap in refills for >30 days during 24 months), and refill
      compliance (medication possession ratio > or = 0.80). RESULTS: The eligible
      cohort included 35,537 women (age, > or = 45 years) who received a bisphosphonate
      prescription. A subgroup with a specified diagnosis of postmenopausal
      osteoporosis was also evaluated. Forty-three percent were refill compliant, and
      20% persisted with bisphosphonate therapy during the 24-month study period.
      Total, vertebral, nonvertebral, and hip fractures were significantly lower in
      refill-compliant and persistent patients, with relative risk reductions of 20% to
      45%. The relationship between adherence and fracture risk remained significant
      after adjustment for baseline age, concomitant medications, and fracture history.
      There was a progressive relationship between refill compliance and fracture risk
      reduction, commencing at refill compliance rates of approximately 50% and
      becoming more pronounced at compliance rates of 75% and higher. CONCLUSIONS:
      Adherence to bisphosphonate therapy was associated with significantly fewer
      fractures at 24 months. Increasing refill compliance levels were associated with
      progressively lower fracture rates. These findings suggest that incremental
      changes in medication-taking habits could improve clinical outcomes of
      osteoporosis treatment.

PMID- 16901024
TI  - Botulinum toxin to improve facial wound healing: A prospective, blinded, placebo
      controlled study.
AB  - OBJECTIVE: To test whether botulinum toxin-induced immobillzation of facial
      lacerations enhances wound healing and results in less noticeable scars. PATIENTS
      AND METHODS: In this blinded, prospective, randomized clinical trial, patients
      were randomized from February 1, 2002, until January 1, 2004, to botullnum toxin
      vs placebo injection into the musculature adjacent to the wound within 24 hours
      after wound closure. Blinded assessment of standardized photographs by
      experienced facial plastic surgeons using a 10-cm visual analog scale served as
      the main outcome measure. RESULTS: Thirty-one patients presenting with traumatic
      forehead lacerations or undergoing elective excisions of forehead masses were
      included in the study. The overall median visual analog scale score for the
      botulinum toxin-treated group was 8.9 compared with 7.2 for the placebo group
      (P=.003), indicating enhanced healing and Improved cosmesis of the experimentally
      immobilized scars. CONCLUSIONS: Botullnum toxin-induced Immobilization of
      forehead wounds enhances healing and is suggested for use in selected patients to
      improve the eventual appearance of the scar.

PMID- 16901025
TI  - Effect of antiviral chemoprophylaxis on adverse clinical outcomes associated with
      cytomegalovirus after liver transplantation.
AB  - OBJECTIVE: To assess t he association be tweencytomegalovirus (CMV) serology of
      donor and recipient and adverse outcomes afterliver transplantation in the era of
      effective antiviral chemoprophylaxis. PATIENTS AND METHODS: We performed a
      retrospective cohort study of 193 consecutive patients undergoing their first
      liver transplantation between February 1998 and July 2000 with targeted and
      preemptive ganciclovir chemoprophylaxis. Patients were divided into 4 groups by
      CMV serology of donor and recipient: donor-/recipient-; donor-/recipient+;
      donor+/recipient+; and donor+/recipient-. Survival to the end points of
      retransplantation, death, or survival to 1 year after transplantation (whichever
      occurred first) was assessed. Rates of bacterial, fungal, and CMV Infection and
      of CMV disease were recorded and compared. RESULTS: No significant differences
      were observed in the rates of retransplantation, death, or survival to 1 year
      among the 4 groups of patients. Despite significantly higher rates of CMV
      infection in the donor+ groups, there were no differences in the rates of
      bacterial or fungal Infection or of CMV disease. Rejection occurred least
      frequently in the donor-/recipient- group. CONCLUSION: The adverse effects of CMV
      on outcomes after liver transplantation have been diminished in the era of
      effective antiviral chemoprophylaxis.

PMID- 16901026
TI  - Temporal trends in prevalence of diabetes mellitus in a population-based cohort
      of incident myocardial infarction and impact of diabetes on survival.
AB  - OBJECTIVE: To determine the temporal trends in prevalence of confirmed diabetes
      mellitus (DM), time from the date DM criteria were met to myocardial infarction
      (MI), and impact of DM on survival. SUBJECTS AND METHODS: A retrospective cohort
      design was used to identify residents of Olmsted County, Minnesota, with incident
      MI from 1979 to 1998. The MI cases were characterized according to prevalent DM.
      Cases with and without DM were followed up for vital status until January 1,
      2003. RESULTS: Of 2171 MI cases, 364 (17%) met criteria for prevalent DM. In the
      age- and sex-adjusted logistic regression models, the odds of prevalent DM
      Increased 3% with each Increasing year between 1979 and 1998 (95% confidence
      Interval [CI], 1%-5%; P=.007). Survival for MI cases with DM was unchanged
      between 1979-1983 and 1994-1998 (P=.74). For all MI cases, age-, sex-, and DM
      adjusted risk of death decreased 3% from 1979 to 1998 (95% CI, 1%-5%) per year
      for 28-day survival (P=.02) and 2% (95% CI, 1%-3%) per year for 5-year survival
      (P=.02). There was a significant adverse effect of DM on 5-year survival after MI
      (age-, sex-, and calendar year-adjusted hazard ratio, 1.70; 95% CI, 1.38-2.09;
      P<.001). The adverse effect of DM persisted after adjusting for other
      cardiovascular disease risk factors, MI severity, and reperfusion therapy (hazard
      ratio, 1.66; 95% CI, 1.34-2.05; P<.001) and was unchanged over time (interaction
      between DM and calendar year, P=-.63). CONCLUSION: These data indicate that the
      prevalence of DM among patients with MI is increasing and that its adverse impact
      on survival after MI remains unchanged.

PMID- 16901027
TI  - The contribution of golf to daily physical activity recommendations: how many
      steps does it take to complete a round of golf?
AB  - To quantify the number of steps adults take during an 18-hole round of golf, we
      recruited 42 healthy volunteers (12 men and 30 women aged 30-80 years) with
      established United States Golf Association handicaps to complete an 18-hole round
      of golf on each of 3 municipal golf courses. Subjects walked each course while
      wearing a pedometer to record step data. Analysis revealed that each golfer took
      a mean +/- SD 11,948 +/- 1781 steps per 18-hole round of golf. Regardless of
      handicap level, sex, or course played, most subjects exceeded 10,000 steps during
      a typical round of golf. Consequently, in most cases, walking 18 holes of golf
      will meet the recommendation to accumulate 10,000 steps per day as part of a
      general physical activity plan.

PMID- 16901028
TI  - Mayo clinic consensus statement for the use of bisphosphonates in multiple
      myeloma.
AB  - Bisphosphonates are effective in the prevention and treatment of bone disease in
      multiple myeloma (MM). Osteonecrosis of the jaw is Increasingly recognized as a
      serious complication of long-term bisphosphonate therapy. Issues such as the
      choice of bisphosphonate and duration of therapy have become the subject of
      intense debate given patient safety concerns. We reviewed available data
      concerning the use of bisphosphonates in MM. Guidelines for the use of
      bisphosphonates in MM were developed by a multidisciplinary panel consisting of
      hematologists, dental specialists, and nurses specializing in the treatment of
      MM. We conclude that intravenous pamidronate and intravenous zoledronic acid are
      equally effective and superior to placebo in reducing skeletal complications.
      Pamidronate is favored over zoledronic acid until more data are available on the
      risk of complications (osteonecrosis of the jaw). We recommend discontinuing
      bisphosphonates after 2 years of therapy for patients who achieve complete
      response and/or plateau phase. For patients whose disease is active, who have not
      achieved a response, or who have threatening bone disease beyond 2 years, therapy
      can be decreased to every 3 months. These guidelines were developed in the
      Interest of patient safety and will be reexamined as new data emerge regarding
      risks and benefits.

PMID- 16901029
TI  - Central arterial pressure and arterial pressure pulse: new views entering the
      second century after Korotkov.
AB  - The ubiquitous brachial cuff method gained widespread clinical acceptance for
      blood pressure recording after confirmation of its prognostic value in 1917. This
      method displaced radial pulse waveform analysis by sphygmography, which also gave
      prognostic Information but was difficult to use. Since that time, brachial cuff
      sphygmomanometry has migrated from the physician's office to 24-hour monitoring
      and home use, with electronic methods replacing the Korotkov sound technique for
      determining systolic and diastolic pressure. Detailed instrumental studies,
      required by regulatory bodies, revealed inaccuracies of all cuff methods for
      recording true intra-arterial pressure. A major source of inaccuracy in assessing
      left ventricular load is the amplification of the pressure wave in its transit
      from the central aorta to upper limb arteries, as extensively studied by Earl H.
      Wood at the Mayo Clinic in Rochester, Minn, in the 1950s. This limitation can be
      overcome by combining newer methods using radial artery waveform analysis in
      conjunction with conventional cuff sphygmomanometry to noninvasively measure the
      central aortic pressure waveforms. Recent studies using radial tonometry have
      proved that this is more effective than conventional manometry in predicting
      cardiovascular events and gauging response to therapy. Measurement of central as
      well as peripheral arterial pressure and physiology is becoming increasingly used
      as an office practice and a laboratory procedure.

PMID- 16901030
TI  - The early history of giant cell arteritis and polymyalgia rheumatica: first
      descriptions to 1970.
AB  - Giant cell arteritis and polymyalgia rheumatica were described separately more
      than 100 years ago. However, the original reports of both conditions were
      neglected for many years. After the article by Horton et al on giant cell
      arteritis in the 1930s and studies published by others in the 1940s, giant cell
      arteritis began to be recognized as a specific disease. In the 1950s and 1960s,
      many of the numerous presentations and complications of giant cell arteritis were
      recorded. In a somewhat similar fashion, physicians became cognizant of
      polymyalgia rheumatica only after several independent descriptions in the 1940s
      and 1950s. The rapid response of both syndromes to glucocorticoid therapy was
      discovered shortly after cortisone's effect on rheumatoid arthritis was
      described. The origin of the proximal aching and stiffness in polymyalgia
      rheumatica was more difficult to understand. The relatively minor findings in the
      joints on physical examination seemed insufficient to account for the severe
      discomfort. As the link between polymyalgia rheumatica and giant cell arteritis
      became apparent, some thought the aching in polymyalgia rheumatica was related to
      vasculitis. The debate about whether proximal synovitis or vasculitis was the
      cause of the symptoms continued after 1970. Although the reason these 2
      conditions were associated was not considered by 1970, the establishment of the
      syndromes as clinically linked entities provided the groundwork for further
      progress in the next decades.

PMID- 16901031
TI  - Prevention of migraine in women throughout the life span.
AB  - Migraine is a common disorder in women. The 1-year prevalence of migraine is 18%
      in women compared with 6% in men. Migraine most commonly occurs during the
      reproductive years, affecting 27% of women 30 to 49 years of age. The
      predominance of this disorder and its social, functional, and economic
      consequences make migraine an important issue in women's health. The hormonal
      milieu has a substantial effect on migraine in women. An understanding of these
      hormonal influences in the various stages of life in females is essential to the
      management and prevention of migraines. This article reviews migraine prevention
      strategies with an emphasis on specific therapies for each stage of a woman's
      life.

PMID- 16901032
TI  - Calcified auricles in a patient receiving hemodialysis.

PMID- 16901033
TI  - 43-year-old man with ear pain, confusion, and agitation.

PMID- 16901034
TI  - Primary surgical therapy for osteonecrosis of the jaw secondary to bisphosphonate
      therapy.
AB  - Bisphosphonate chemotherapy is commonly used in the treatment of bone diseases
      such as osteoporosis, Paget disease, and multiple myeloma and to limit bone pain
      and hypercalcemia associated with malignant metastatic bone lesions. The
      introduction of bisphosphonate therapy has improved the quality of life in a vast
      majority of patients, showing clear medical efficacy. However, since 2003 a
      growing number of reports have described necrotic bone lesions (osteonecrosis of
      the jaw [ONJ]) affecting maxillofacial bones in patients who have received
      chemotherapy with intravenous bisphosphonate therapy. Unfortunately, the
      development of ONJ has been refractory to conventional treatment modalities.
      Several treatment options have been proposed for ONJ, most of which focus
      primarily on conservative management with local irrigation and empirical long
      term antibiotic therapy. However, results of treatment have been associated with
      high failure rates, progression of disease, and continued decline in patients'
      quality of life. We describe 2 patients in whom primary surgical salvage was
      performed successfully for ONJ. Our experience indicates that with appropriate
      technique, primary surgical treatment may offer benefit to selected patients with
      ONJ.

PMID- 16901035
TI  - Chronic lymphocytic leukemia: diagnosis and treatment.
AB  - Traditionally, the goal of therapy in chronic lymphocytic leukemia (CLL) has been
      palliative, with first-line therapy using alkylating agents and/or involved field
      radiotherapy (depending on the stage of disease and sites of involvement) because
      of the older age of affected patients and the low rate of complete remissions
      (CRs) with no improvement in overall survival despite treatment. With increasing
      knowledge about the biology, molecular genetics, and prognostic factors of the
      disease, the philosophy of care for patients with CLL has evolved from palliation
      to aiming for a potential cure, especially in younger patients. Furthermore,
      multiple treatment options have emerged, including purine analogues, monoclonal
      antibodies, and potentially stem cell transplantation. These have been associated
      with higher frequencies of CRs and longer durations of responses compared to
      conventional chemotherapy. In addition, a subset of patients treated with
      chemoimmunotherapy can achieve durable CRs and molecular remissions. This may
      translate into improved disease-free survival and potentially a "cure." Because
      of the heterogeneous nature of CLL, new prognostic markers are currently being
      incorporated into clinical trials to determine their role in routine clinical
      practice. This review summarizes current therapeutic regimens that are being
      evaluated in patients with CLL and management of disease-related complications.

PMID- 16901036
TI  - Problems with measurements of hemoglobin A1c.

PMID- 16901038
TI  - Aortic valve replacement for aortic stenosis after previous coronary artery
      bypass grafting: could early reoperation be prevented?
AB  - BACKGROUND AND AIM OF THE STUDY: The study aim was to examine, retrospectively,
      the risk of accelerated progression of aortic stenosis (AS) and outcome after
      aortic valve replacement (AVR) in patients who had undergone previous coronary
      artery bypass graft (CABG) surgery. METHODS: Between 1994 and 2004, 81 patients
      with mild-to-moderate AS at the time of CABG underwent subsequent AVR. The mean
      EuroScore was 10.8 +/- 1.8. The population was divided into three subgroups
      according to the time interval between AVR and CABG: group A, < 5 years (n = 23);
      group B, 5-10 years (n = 34); and group C, > 10 years (n = 24). RESULTS: Mean age
      at the time of CABG was 70 +/- 5, 64 +/- 6 and 58 +/- 5 years in groups A, B, and
      C, respectively. The peak transvalvular gradient was < or = 30 mmHg in 65
      patients (80.2%), and 30-50 mmHg in 16 (19.7%). Operative mortality after AVR was
      16% in the overall population (30%, 11.7%, and 8.6% in groups A, B, and C,
      respectively). The mean time interval between CABG and AVR was 8.9 +/- 5.2 years.
      By multivariate analysis, a peak transvalvular gradient > or = 30 mmHg (p =
      0.003), moderate calcifications with moderately-to-severely limited valve motion
      (p = 0.05), and left ventricular hypertrophy (LVH) (p = 0.005) were independent
      predictors of AVR within five years of CABG surgery. Systemic vascular
      atherosclerotic disease was a predictor of rapid disease progression by
      univariate analysis, and a predictor of operative mortality by multivariate
      analysis. CONCLUSION: Because of the high mortality associated with repeat
      operations within five years, AVR should be considered at the time of CABG in
      patients aged < or = 75 years, with a peak transvalvular gradient > 30 mmHg,
      moderately prominent calcifications with moderately to severely limited valve
      motion, and LVH.

PMID- 16901037
TI  - Left ventricular volume shifts and aortic root expansion during isovolumic
      contraction.
AB  - BACKGROUND AND AIM OF THE STUDY: Aortic valve opening involves conformational
      changes of the aortic root, including the ventricular-aortic junction (VAJ),
      sinotubular junction (STJ), and cusps. Moreover, the aortic root is contiguous
      with the left ventricular outflow tract (LVOT), which changes diameter throughout
      the cardiac cycle. Aortic root expansion prior to valve opening facilitates
      outward displacement of aortic cusp attachments, which helps flatten the cusps,
      thereby reducing cusp stress and fatigue, ultimately enhancing functional valve
      durability. The mechanisms underlying aortic root expansion prior to valve
      opening, however, remain incompletely characterized. The study aim was to
      establish a link between such aortic root expansion and intraventricular volume
      shifts into the LVOT during isovolumic contraction (IVC). METHODS: Miniature
      radiopaque markers were implanted on the left ventricle, VAJ, STJ, and aortic
      cusps of six sheep. After one week, 3-D marker coordinates were obtained using
      biplane videofluoroscopy (60 Hz). Triangular areas at the VAJ and STJ were
      calculated; LV main chamber (non-LVOT) and LVOT volumes were calculated using
      multiple tetrahedra. End-diastole was defined as the peak of the
      electrocardiogram R-wave, and end-IVC when aortic cusp separation began. RESULTS:
      During IVC, blood within the left ventricle was redistributed to the LVOT: mean
      LVOT volume was increased (+0.2 +/- 0.1 ml, p = 0.009) as non-LVOT volume fell (
      0.8 +/- 0.4 ml, p = 0.006). Concomitantly, the aortic root expanded as both VAJ
      and STJ areas increased (+0.23 +/- 0.12 cm2 (p = 0.005) and +0.25 +/- 0.14 cm2 (p
      = 0.007), respectively) prior to aortic cusp separation. CONCLUSION: Aortic root
      expansion prior to valve opening is closely related to intraventricular volume
      shifts into the LVOT during IVC. Such volume shifts may 'prime' the aortic valve
      for ejection. These findings expand our understanding of cardiac dynamics by
      showing that blood acts as a coupling link between various cardiac units.
      Preservation of these normal aortic root dynamics may enhance the efficacy and
      durability of aortic surgical interventions.

PMID- 16901039
TI  - Outcome after aortic valve replacement in young adults: is patient profile more
      important than prosthesis type?
AB  - BACKGROUND AND AIM OF THE STUDY: The optimal prosthesis choice in young adults
      requiring aortic valve replacement (AVR) remains controversial. The study aim was
      to determine whether implanted prosthesis type is an important determinant of
      outcome after AVR in young adults. METHODS: Between 1991 and 2001, 414 young
      adults (mean age 40 +/- 11 years; range: 16-55 years) underwent a total of 438
      consecutive AVRs using 204 mechanical prostheses (MP), three bioprostheses (BP),
      150 allografts (AL), and 81 autografts (AU). The perioperative characteristics,
      early and late mortality, occurrence of valve-related events and predictors of
      adverse outcome and prosthesis selection, were evaluated. RESULTS: Mean patient
      ages were 45 years for MP, 50 years for BP, 39 years for AL, and 31 years for AU.
      MP selection was associated with older age, impaired left ventricular function
      (LVF) and concomitant mitral valve surgery (concMVS); AL selection with ascending
      aortic aneurysm, active endocarditis, and Marfan's disease; and AU selection with
      younger age, prior balloon valvuloplasty and isolated valve disease. Hospital
      mortality was 2.3% (n = 10). During follow up (97% complete) 30 patients died.
      Ten-year survival was better for AU (96 +/- 2%) compared to MP (84 +/- 4%) and AL
      (92 +/- 2%). Prosthesis type was not predictive of late mortality; rather,
      predictors of increased late mortality were prior aortic valve surgery, impaired
      LVF, concMVS, and older patient age. Ten-year freedom from bleeding and
      thromboembolism was 89 +/- 3% for MP versus 94 +/- 3% for AL and 99 +/- 1% for AU
      (p = 0.054). Ten-year freedom from reoperation was 95 +/- 2% for MP versus 79 +/-
      5% for AL and 87 +/- 5% for AU (p = 0.003). CONCLUSION: Survival after AVR in
      young adults in Rotterdam was mainly determined by patient-related factors, and
      not by prosthesis type. A randomized controlled trial is necessary to determine
      whether valve prosthesis type indeed plays a crucial role in improving survival
      in young adult patients.

PMID- 16901040
TI  - Aortic annuloplasty with aortic root reconstruction to prevent patient-prosthesis
      mismatch.
AB  - Part of the ongoing argument concerning patient-prosthesis mismatch (PPM)
      following aortic valve replacement (AVR) is due to the perception that aortic
      annulus enlargement procedures increase the risk and technical difficulty of
      aortic valve surgery. Here, an aortic root reconstruction that involves
      enlargement of the annulus and tailoring of the aortic root to accommodate larger
      stented prostheses is presented that has been personally performed in 196
      patients with no technique-related surgical deaths or complications, and thus can
      be carried out without additional risk. This aortic root enlargement aortoplasty
      and annuloplasty method can be calibrated to all AVRs involving stented
      manufactured prostheses when these are deemed the prosthesis of choice for the
      patient with a relatively small annulus and/or aortic root, severe left
      ventricular hypertrophy, compromised LV function or a very active lifestyle, to
      achieve predicted EOA values > or = 1.00 cm2/m2.

PMID- 16901041
TI  - Aortic valve calcification as quantified with multislice computed tomography
      predicts short-term clinical outcome in patients with asymptomatic aortic
      stenosis.
AB  - BACKGROUND AND AIM OF THE STUDY: Aortic valve calcification may be an independent
      risk factor for adverse clinical outcome. The study aim was to assess the
      predictive value of possible risk factors, including the severity of aortic valve
      calcification as quantified with 16-multislice computed tomography (MSCT) for
      adverse short-term clinical outcome in patients with asymptomatic, degenerative
      aortic stenosis (AS). METHODS: Possible risk factors for adverse short-term
      clinical outcome were prospectively tested in 34 consecutive patients with
      asymptomatic AS as follows: (i) aortic valve calcium (AVC) score as quantified
      with MSCT; (ii) echocardiographic parameters--aortic valve area (AVA) calculated
      with continuity equation, mean and maximal transvalvular pressure gradients, end
      diastolic septal wall diameter; and (iii) laboratory tests (brain natriuretic
      peptide (BNP), C-reactive protein (CRP)). RESULTS: Within 18-24 months of follow
      up, 11 of 34 patients developed a major adverse clinical outcome. Ten patients
      suffered from onset of symptoms accompanied by hemodynamic progression, and one
      patient died from sudden cardiac death. Six of these 10 patients underwent aortic
      valve replacement, one patient declined surgery, and three patients were not
      accepted for surgery (one of these died suddenly shortly afterwards). The aortic
      valve calcium score was the strongest predictor of a major adverse clinical event
      (p < 0.001) among all parameters assessed (1,928 +/- 789 versus 5,111 +/- 2,409
      Agatston units). The plasma level of BNP (p = 0.003), mean transvalvular pressure
      gradient (p = 0.002) and AVA (p = 0.003) were also risk factors for adverse
      clinical outcome. CONCLUSION: The AVC score as quantified with MSCT predicted
      adverse short-term clinical outcome in patients with asymptomatic AS. In patients
      with severe aortic valve calcification, close follow up examinations are
      mandatory, and early elective surgery may be considered even in the absence of
      symptoms. MSCT provides a comprehensive non-invasive imaging approach for risk
      stratification in patients with asymptomatic AS.

PMID- 16901042
TI  - Nanobacteria to promote degenerative aortic valve stenosis?

PMID- 16901043
TI  - Lower serum calcium levels are associated with greater calcium hydroxyapatite
      deposition in native aortic valves of male patients with severe calcific aortic
      stenosis.
AB  - BACKGROUND AND AIM OF THE STUDY: The study aim was to evaluate the relationship
      between serum calcium levels and the degree of calcification found in stenotic
      aortic valves. METHODS: Using atomic absorption spectroscopy, the hydroxyapatite
      content of 228 excised human stenotic aortic valves was determined and expressed
      as a percentage of valve mass. Left heart catheterization preceded valve
      replacement. In addition, serum levels of calcium and creatinine were determined
      before native calcific aortic valve excision. RESULTS: Valves from male patients
      contained more hydroxyapatite than those of female patients (26 +/- 9 versus 22
      +/- 9 mass%; p < 0.001). Patients presenting with lower serum calcium levels
      showed a slight trend towards higher levels of valve calcification (r = -0.15, p
      = 0.026), but this association appeared only within the subgroup of male
      patients. Male patients with lowest serum calcium levels displayed greatest
      valvular hydroxyapatite deposition (1st calcium tertiary: 29.5 +/- 8.9 mass%
      versus 2nd calcium tertiary 26.4 +/- 7.8 mass% versus 3rd calcium tertiary 21.4
      +/- 8.9 mass%; n = 122; p = 0.001; r = -0.25; p = 0.006). This association was
      even more distinct in male patients with normal serum creatinine levels.
      Furthermore, serum calcium was inversely and significantly associated with serum
      C-reactive protein in male patients (r = - 0.34; p < 0.001). CONCLUSION: Serum
      calcium levels appear to be inversely related to valve calcification in patients
      with severe calcific aortic stenosis (AS). This finding indicates the importance
      of systemic calcium metabolism in calcific AS, independent of manifest disorders
      of calcium metabolism or renal function. Interestingly, this association was
      evident only in male patients, suggesting a gender-dependent pathogenesis.

PMID- 16901044
TI  - Myocardial infarction with ventricular septal rupture complicating elective
      aortic valve replacement.
AB  - Herein is described the case of a 79-year-old woman who underwent elective aortic
      valve replacement. The procedure was complicated by a particulate embolism into
      the left anterior descending artery leading to a myocardial infarction,
      complicated by ventricular septal rupture. Subsequently, the patient was
      reoperated on and the septal defect closed successfully, with an uneventful
      recovery.

PMID- 16901045
TI  - Delayed systolic anterior motion after mitral valve repair.
AB  - A rare case of systolic anterior motion (SAM) after mitral valve repair is
      described. A temporary postoperative left ventricular (LV) dysfunction protected
      against this complication during the early postoperative period. Only on day 9
      postoperatively did the left ventricle recover and SAM develop, with significant
      obstruction of the LV outflow tract. Subsequently, mitral valve replacement was
      required. This case demonstrates the importance of the LV geometrical
      relationships that predispose to this complication.

PMID- 16901047
TI  - TEE: the 'roadmap' for mitral valve repair.

PMID- 16901046
TI  - Combined atrial fibrillation ablation with mitral valve surgery.
AB  - BACKGROUND AND AIM OF THE STUDY: The study aim was to evaluate the efficacy and
      outcome of radiofrequency (RF) atrial fibrillation (AF) ablation in patients
      undergoing mitral valve (MV) surgery. METHODS: Between March 2002 and December
      2004, 61 patients (mean age 65.4 +/- 10 years) underwent isolated endo-left
      atrial AF ablation using a unipolar RF device (Cardioblate; Medtronic, USA) in
      conjunction with 34 MV repairs and 27 MV replacements. AF was paroxysmal in 13
      patients (21%), and permanent in 48 (79%), with a mean duration of 3.6 +/- 3.5
      years. The etiology was degenerative in 35 patients (57%), rheumatic in 17 (28%),
      and ischemic in nine (17%). All patients received amiodarone postoperatively.
      RESULTS: No patients died during the study, and there were no thromboembolic
      complications. All patients had intraoperative conversion. Forty-one patients
      (67%) presented with postoperative relapse; definitive conversion was achieved in
      34 (83%) cases within three months. The overall success rate was 75.4% at 14 +/-
      8.8 months; success was greater in the MV repair group (85%) than in the MV
      replacement group (66.7%), though not significantly so (p = 0.09). Factors
      associated with definitive conversion included smaller left atrial size (p =
      0.007), decreased left ventricular end-diastolic diameter (p = 0.04), and NYHA
      class I (p = 0.05). Age, AF duration and etiology were not associated with
      conversion, but associated coronary artery bypass grafting showed a strong trend
      towards significance (p = 0.07). In these patients, AF duration did not predict
      conversion to sinus rhythm. CONCLUSION: Combined AF ablation with MV surgery is
      safe and effective. Although AF ablation seems more beneficial with MV repair,
      the success rate may vary significantly according to patient characteristics.

PMID- 16901048
TI  - Echocardiographic measurements alone do not provide accurate non-invasive
      selection of annuloplasty band size for robotic mitral valve repair.
AB  - BACKGROUND AND AIM OF THE STUDY: Successful mitral valve repair (MVP) is
      dependent on accurate annuloplasty band sizing. This is difficult and time
      consuming when performed via port-access, or through a 4-cm minithoracotomy used
      in robotically assisted MVP. With the goal of moving toward a less-invasive
      approach and minimizing cross-clamp time, an attempt was made to determine
      annuloplasty band size using transesophageal echocardiography (TEE) alone.
      METHODS: The intertrigonal distance (ITD) was determined by dividing the left
      ventricular outflow tract diameter (LVOT: measured on standard midesophageal
      aortic valve long-axis view) by 0.8. The ITD was compared to a nomogram developed
      to select the best Cosgrove-Edwards annuloplasty band size. RESULTS: Between July
      and October, 2004, 11 patients (mean age 52.6 +/- 17.9 years; four Barlow's
      valves with bileaflet prolapse, four posterior leaflet prolapses, one anterior
      leaflet prolapse, one rheumatic, one dilated annulus) undergoing robotically
      assisted MVP had the annuloplasty band chosen using TEE alone. Seven patients
      (63.6%) had no or mild mitral regurgitation (MR) on postoperative TEE. Three
      patients (27.2%) had some systolic anterior motion (SAM), with one (Barlow's
      valve) requiring a second repair (same operation). One patient (9.1%, rheumatic)
      had grade 2+ MR on postoperative TEE. CONCLUSION: In this small case series, a
      substantial proportion of patients had suboptimal immediate postoperative
      results. This suggests that selection of the annuloplasty band should not be
      based on a single echocardiographic variable as it depends on the etiology of the
      MR, and other dimensions of the mitral valve. Further studies are ongoing to
      develop a non-invasive method for the selection of annuloplasty band size.

PMID- 16901049
TI  - Posterior leaflet preservation in mitral valve prolapse: a new approach to mitral
      repair.
AB  - The most common repair technique for P2 prolapse is quadrangular resection of the
      posterior leaflet associated with a plication of the mitral annulus or with a
      sliding plasty. Although effective, these techniques do not respect the anatomy
      of the mitral valve, especially the physiological role of the posterior leaflet.
      Herein is described another technique which does not include P2 removal, thus
      preserving the posterior leaflet mobility. This technique represents a new
      approach to mitral valve repair that respects the motion of the two leaflets,
      allowing a more physiological opening of the mitral valve.

PMID- 16901050
TI  - An evaluation of the Ross operation in adults.
AB  - BACKGROUND AND AIM OF THE STUDY: Pulmonary autograft replacement of the aortic
      valve (the Ross operation) is the operation of choice in infants and children.
      Although this procedure can offer theoretical advantages at any age, its use in
      adults remains controversial. METHODS: A total of 264 consecutive patients (203
      males, 61 females; mean age 35.0 +/- 11.5 years; range: 18-66 years) was studied.
      These patients underwent the Ross operation at two institutions and were followed
      up for a total of 1,634 patient-years. The etiology was mainly congenital (52%),
      degenerative (22%), and rheumatic (8%). Among patients, 21% underwent prior
      aortic valve replacement. RESULTS: Thirty-day mortality was 2.3% (n = 6), and
      four more patients died during follow up (mean follow up 6.2 years; range 0-15.4
      years). Cumulative survival at five years was 96.8%, and at 10 years was 95.4%.
      Eleven patients underwent reoperation on the aortic valve; this was due to
      progressive dilatation and aortic regurgitation in 10 cases, and to dissection of
      the arterial wall of the autograft in one case. Overall freedom from pulmonary
      homograft reoperation was 94.9% at 10 years, and for autograft reoperation was
      92.9%. Estimated freedom from autograft reoperation at Harefield was 98.6% at
      five and 10 years, and at Rotterdam 96.0% at five years and 88.2% at 10 years (p
      = 0.10, Tyrone-Ware). No risk factors for early and late mortality and
      reoperation were detected. CONCLUSION: In this combined series, the Ross
      operation in adult patients resulted in excellent survival and acceptable
      reoperation rates. A prospective randomized trial is proposed to study whether
      this observation truly reflects the potential advantages of the Ross procedure,
      or whether it is caused by patient selection.

PMID- 16901051
TI  - Anti-HLA antibodies after cryopreserved allograft valve implantation does not
      predict valve dysfunction at three-year follow up.
AB  - BACKGROUND AND AIM OF THE STUDY: As the cause of allograft heart valve
      degeneration is poorly understood, the study aim was to investigate the host
      antibody response to allograft valve implantation. METHODS: Sera were obtained
      from 92 recipients of allograft heart valves (61 pulmonary, 31 aortic). Sera were
      tested for anti-HLA class I antibodies by ELISA and complement-dependent
      cytotoxicity (CDC) methods, and anti-HLA class II antibodies by ELISA.
      Specificities of recipient anti-HLA class I antibodies were defined by standard
      CDC testing against a panel of T lymphocytes from 80 blood donors. Donor valve
      HLA typing was performed on stored donor DNA samples using molecular methods. The
      presence of donor-specific anti-HLA class I antibodies was hence defined in
      recipient sera. The presence of anti-HLA antibodies and donor-specific anti-HLA
      class I antibodies were correlated with function of allograft valves at the most
      recent echocardiographic follow up. RESULTS: At a mean of 3.0 years (range: 0.3
      5.4 years) after allograft implantation, 96% (87/92) and 82% (75/92) of patients
      were positive for anti-HLA class I and II antibodies, respectively, by ELISA
      testing. Some 68% (61/90) of patients were positive for anti-HLA class I antibody
      (PRA > 5%) by CDC testing. PRA levels decreased with greater postoperative
      interval (r = -0.31, p = 0.003). In 68 recipients where donor HLA type was
      defined, 54% (37/68) of patients had antibodies specific to at least one donor
      HLA class I antigen. In 87 patients with a recent echocardiographic examination
      available for analysis (at a mean of 3.5 +/- 1.6 years postoperatively), there
      was no association between valve dysfunction and antibody status. CONCLUSION:
      Anti-HLA class I and II antibodies were detected by ELISA methods in most
      patients after allograft implantation extending to 5.4 years. The clinical
      significance of these findings is unclear, as no correlation was found between
      the prevalence of anti-HLA antibody and echocardiographic parameters of valve
      dysfunction at a mean of 3.5 years follow up.

PMID- 16901052
TI  - Clinical experience with the 3F stentless aortic bioprosthesis: one-year follow
      up.
AB  - BACKGROUND AND AIM OF THE STUDY: The 3F equine aortic bioprosthesis is a new
      stentless valve which is currently undergoing evaluation in a multicenter
      clinical trial and is considered to have superior hemodynamic performance. Herein
      is reported the authors' initial experience with the 3F valve, focusing on the
      hemodynamic performance of the device. METHODS: Between March 2002 and October
      2003, 35 patients (age range 61-86 years) underwent aortic valve replacement with
      the 3F valve implanted in the subcoronary position. Evaluation of valve
      hemodynamic performance was assessed at discharge (postoperative day 5 +/- 2), at
      3-6 months, and at 11-14 months' follow up by means of transthoracic
      echocardiography. The mean preoperative transvalvular pressure gradient was 63 +/
      14 mmHg. Before surgery, all patients were in NYHA class III or IV, despite
      aggressive medical treatment. Five patients underwent concomitant coronary artery
      bypass grafting. RESULTS: The implanted valve sizes ranged from 21 to 29 mm.
      There were no operative deaths and no major perioperative complications. After 12
      months, mean pressure gradients for the 23-, 25-, 27- and 29-mm valves were 13,
      13, 12 and 9 mmHg, respectively. Mean systolic pressure gradients and NYHA class
      were improved significantly after surgery. Mild signs of hemolysis and minimal
      central regurgitation were detected in some patients, but were of no clinical
      importance. Valve dysfunction or mechanical failure did not occur during the
      follow up period. CONCLUSION: Because of its flexible structure, the 3F aortic
      bioprosthesis is simple to implant, and no major adverse effects have been
      associated with such valve implantation at the authors' center. Transprosthetic
      gradients appeared to regress at 6-12 months' follow up. The durability of the
      device is yet to be established in ongoing long-term trials.

PMID- 16901053
TI  - Hemodynamics of high-performance bileaflet valves: comparison to simulated
      clinical Doppler measurements.
AB  - BACKGROUND AND AIM OF THE STUDY: The newly designed, so-called 'high performance'
      bileaflet heart valve prostheses are suggested to be especially beneficial in
      small sizes. Herein, valvular energy loss and transvalvular gradients were
      evaluated using an in-vitro pulsatile flow model for aortic prostheses (St. Jude
      Medical Regent and On-X, sizes 19-23 mm). Gradients were compared with simulated
      clinically derived Doppler gradients to determine the extent of pressure
      recovery. METHODS: Valves were analyzed using a pulsatile circulatory mock loop
      simulator at heart rates of 70 and 110 bpm, and at cardiac outputs of 2, 4, 5,
      and 7 l/min, respectively (FDA requirements). Measurements consisted of computed
      calculation of energy loss and determination of mean pressure gradient by
      pressure transducers. A Doppler probe was mounted into the device for
      simultaneous measurement of Doppler gradient according to the Bernoulli equation.
      RESULTS: The systolic energy loss of the SJM Regent valve averaged 5.0 +/- 4.6%
      (range: 0.2 to 14.9%) of the effective forward energy, while that for the On-X
      valve was 6.5% (range: 0.7-22.8%). Total energy loss was 9.9% (range: 4.8-22.1%)
      for the SJM Regent valve, and 12.7% (range: 6.5-27.7%) for the On-X valve. The
      average extent of pressure recovery was 64% for both valve types. CONCLUSION: All
      tested valves were characterized by excellent hemodynamic performance, with
      overall low systolic and total energy losses, but results were slightly favorable
      for the SJM Regent valve. Valve performance was concluded to be much better than
      expected by clinical routine Doppler measurements, which significantly
      overestimates transvalvular gradients; this effect was explained by pressure
      recovery. Nevertheless, Doppler gradient remains a valuable follow up technique
      for patients with heart valve prostheses.

PMID- 16901054
TI  - Early wear development in a novel mechanical heart valve prosthesis made from
      polymeric materials.
AB  - BACKGROUND AND AIM OF THE STUDY: Currently, 95% of all implanted mechanical heart
      valve prostheses are constructed completely, or at least partially, from
      pyrolytic carbon. In order to develop a mechanical heart valve prosthesis made
      from alternative materials, a special hinge design was tested which enabled the
      integration of wear-resistant tribomaterials into the highly loaded hinges of
      leaflets. METHODS: The wear behavior of different material couples was
      investigated in vitro. Wear testing was performed using a specially designed
      durability tester that controlled the pressure difference across the closed heart
      valve prosthesis in a water-glycerol mixture with blood analog viscosity.
      Conditions were set according to FDA and ISO standards for heart valve testing.
      Qualitative assessment of wear behavior was performed using light microscopy and
      scanning electron microscopy at intervals of 10, 40, and each subsequent 50
      million cycles. RESULTS: None of the investigated heart valve prostheses failed
      during the durability tests. Compared to the reference valve made from polymeric
      materials, wear especially in the hinges could be reduced to an acceptable level
      by integrating wear-resistant tribomaterials into the leaflets. CONCLUSION: A
      leaflet design which enables the integration of tribomaterials into the highly
      loaded hinges of leaflets leads to an optimization of wear behavior of a
      mechanical heart valve prosthesis made from polymeric materials. Abrasive wear in
      the hinges may be reduced to an acceptable level for the functionality of the
      heart valve prosthesis. Durability tests will be continued in order to confirm
      the promising wear behavior of this novel heart valve prosthesis.

PMID- 16901055
TI  - Management of active infective endocarditis complicated by large vegetations.

PMID- 16901056
TI  - Early surgery or medical treatment in endocarditis complicated by embolism from a
      large, mobile vegetation? A case-based discussion.
AB  - Patients with endocarditis who present after embolism from a large, mobile
      vegetation pose a clinical dilemma: should they be managed with early surgery
      with the aim of preventing further emboli, or should a medical strategy be
      employed that avoids the morbidity and mortality associated with surgery but
      which risks further emboli? The management of such a patient is discussed in the
      context of the published literature regarding embolic risk in endocarditis.

PMID- 16901058
TI  - Early postoperative anticoagulation after mechanical valve replacement: a
      Canadian survey.
AB  - BACKGROUND AND AIM OF THE STUDY: The optimal approach to anticoagulation during
      the early postoperative period after mechanical valve replacement, by which early
      thromboembolism is prevented without bleeding complications, is not yet known.
      The study aim was to examine the practice patterns of Canadian cardiac surgeons
      with regard to early postoperative anticoagulation after mechanical valve
      implantation. METHODS: A questionnaire was sent to 100 Canadian cardiac surgeons
      in July 2004, and 57 responses were received. Data were collected regarding the
      approaches to early postoperative anticoagulation following uncomplicated
      isolated mechanical aortic valve replacement (AVR) and mitral valve replacement
      (MVR). RESULTS: Heparin was administered routinely after AVR and MVR by 63% and
      68% of surgeons, respectively. This was most commonly initiated on postoperative
      day (POD) 1, and given either subcutaneously (AVR, 28%; MVR, 25%) or
      intravenously (AVR, 33%; MVR, 42%). Alternatively, low-molecular-weight heparin
      was used by 21% and 23% of surgeons after AVR and MVR, respectively. Oral
      warfarin was usually started on POD 1 (72% and 68%, respectively), with 40%
      prescribing an initial dose between 2.5 and 5.0 mg, and 51% administering between
      5.1 and 7.5 mg. When heparin was not used, oral anticoagulation was more often
      administered earlier (AVR, p = 0.003; MVR, p = 0.006), but not at higher doses
      (AVR, p = 0.07; MVR, p = 0.2). Following surgery, aspirin was prescribed by 61%
      and 65% of surgeons after AVR and MVR, respectively. CONCLUSION: The study
      results highlighted a significant variability in the management of early
      postoperative anticoagulation after mechanical valve implantation. The clinical
      impact of these findings is unknown, and can only be assessed through a
      prospective trial.

PMID- 16901057
TI  - Our inability to predict thromboembolic events after prosthetic valve surgery.
AB  - BACKGROUND AND AIM OF THE STUDY: Thromboembolic and bleeding complications
      detract from outcome for patients with prosthetic heart valves. The study aim was
      to investigate whether measurement of coagulation activation markers and
      transcranial Doppler ultrasound microembolic signals (MES) could identify
      patients at subsequent higher risk of thromboembolism or bleeding events.
      METHODS: A total of 526 patients (mean age 66 years; 266 males, 260 females) who
      underwent elective valve replacement surgery was enrolled between April 1999 and
      October 2002. Clinical assessment and blood sampling for coagulation activation
      markers was performed preoperatively and at three and 12 months postoperatively.
      Transcranial Doppler MES were recorded in the first 144 patients. Status was
      reviewed between 21st April and 9th June 2005, with 99.4% follow up. RESULTS:
      Among patients, 62% had an aortic valve replaced, and mechanical valves
      constituted 60% of all implants. The mean follow up was 3.61 years; total follow
      up was 1,899.2 patient-years (pt-yr). In total, 115 patients died, while 61
      experienced a total of 80 thromboembolic events: linearized event rates were
      3.94% (mechanical valves) and 4.4% (bioprostheses). There was no difference
      between mitral and aortic implants, or among bileaflet, tilting-disc mechanical
      and porcine valves. Atrial fibrillation was not influential. Coagulation
      activation markers were not associated with thromboembolic events, except for an
      elevated von Willebrand factor (vWF), which was associated with a five-fold
      increase in embolic event rate. Fifty-one patients experienced 59 bleeding
      events; eight patients experienced multiple events. Linearized event rates were
      3.37% (mechanical valves) and 2.49% (bioprostheses). The INR was suboptimal in 44
      58% of patients. Transcranial Doppler MES were not associated with blood
      coagulation markers or thromboembolic events. CONCLUSION: Coagulation activation
      markers (except vWF) and MES did not predict thromboembolic events in valve
      replacement patients. Thromboembolic and bleeding event rates for West of
      Scotland patients generally exceeded reported rates: suboptimal anticoagulation
      appeared common and most likely influenced thromboembolic and bleeding event
      rates more than any other factor.

PMID- 16901059
TI  - Right-sided cardiac involvement in osteogenesis imperfecta.
AB  - Skeletal manifestations are the hallmark of the osteogenesis imperfecta group of
      disorders. Extraskeletal involvement may, however, contribute significantly to
      morbidity. Structural cardiovascular anomalies reported in osteogenesis
      imperfecta include aortic root dilatation and aortic and mitral valve
      dysfunction. Herein is reported the first case of involvement of the right side
      of the heart in osteogenesis imperfecta.

PMID- 16901060
TI  - Fibrolelastoma and Lambl's excrescences: localization, morphology and
      pathogenesis, differential diagnosis and infection.

PMID- 16901061
TI  - [A patient who refused treatment after self-poisoning with paracetamol].
AB  - Two patients, a 20-year-old man and a 33-year-old woman, were admitted with
      paracetamol poisoning. Both patients refused treatment initially but eventually
      complied. The man had a paracetamol concentration of 47.5 mg/l 2.5-5.0 h after
      ingestion, so antidote treatment was not considered necessary. The woman had a
      paracetamol concentration of 1.37 mg/l 32 h after ingestion and elevated liver
      enzymes and was treated with N-acetylcysteine intravenously. Both patients
      recovered. When a patient refuses treatment, the physician must judge whether the
      patient is capable of making that decision by himself or herself. In the acute
      setting of attempted suicide, the patient is either incapable of deciding or
      there is not enough time to make a proper judgement. This means that consent for
      treatment should be sought from a legal representative of the patient. If this is
      impossible and treatment is necessary to prevent serious harm, the physician must
      judge whether the advantages of treatment outweigh the disadvantages of enforced
      treatment. If this is the case, as in serious paracetamol poisoning, the patient
      must be treated against their will, even if it requires sedation.

PMID- 16901062
TI  - [The use of angiotensin converting enzyme (ACE) inhibitors during pregnancy
      clearly increases the risk of congenital malformations].
AB  - Recently, an important study was published concerning the possible teratogenic
      effects of angiotensin converting enzyme (ACE) inhibitors. Non-diabetic women who
      had used an ACE inhibitor during the first trimester of pregnancy had a
      significantly greater chance of giving birth to an infant with congenital
      malformations than women who had used no or other antihypertensive agents. The
      excess risk remained even after adjusting for several potential confounders. The
      results indicate that ACE inhibitors should not be prescribed to women who are
      likely to become pregnant during the course of treatment.

PMID- 16901063
TI  - [Rapid prenatal diagnosis of chromosomal abnormalities; limitations and
      possibilities].
AB  - In the past, prenatal diagnosis of chromosomal abnormalities has been achieved
      using a microscope to make a visual assessment of the chromosomes in foetal cells
      which had been obtained by invasive procedures. The results were usually not
      available until 10-14 days later. Now molecular techniques have become available
      which provide a result within 24-48 hours. The first generation of these
      techniques combines speed with a focus on a limited number of frequent and
      important chromosomal abnormalities. Examples include fluorescence in-situ
      hybridisation (FISH), quantitative polymerase chain reaction (PCR) and multiple
      ligation-dependent probe amplification (MLPA). One drawback, therefore, is that
      other clinically significant chromosomal abnormalities will not be detected. More
      recently other new techniques have been making their appearance, such as array
      comparative genomic hybridisation (CGH), which will allow the detection of
      clinically significant submicroscopic aberrations.

PMID- 16901065
TI  - [Diagnostic image (283). A man with a swollen tongue].
AB  - A 70-year-old man presented with a swollen tongue caused by an angiotensin
      converting enzyme inhibitor.

PMID- 16901064
TI  - [Phosphodiesterase inhibitors: effectiveness and new applications].
AB  - Three different phosphodiesterase 5 (PDE5) inhibitors are currently available for
      the treatment of erectile dysfunction: sildenafil, vardenafil and tadalafil. The
      differences between these 3 are limited: tadalafil has a long duration of action,
      while vardenafil has a rapid onset of action after intake. Various studies have
      suggested that there is an improvement in the partners' sex lives when men use a
      PDE5 inhibitor for erectile dysfunction. The introduction of PDE5 inhibitors has
      renewed the interest in PDE inhibitors in general, for example in the treatment
      of pulmonary hypertension. In the near future PDE inhibitors may be used for
      various disorders as chronic obstructive pulmonary disease, benign prostatic
      hyperplasia, hypertension and coronary heart disease.

PMID- 16901066
TI  - [Chronic indwelling pleural catheter for malignant pleural effusion in 25
      patients].
AB  - OBJECTIVE: To describe the experience with an indwelling pleural catheter in
      patients with pleuritis carcinomatosa. DESIGN: Prospective follow-up study.
      METHOD: The placement of an indwelling pleural catheter was considered as a
      treatment possibility for patients who presented with symptomatic accumulation of
      pleural fluid that returned following previous drainage or pleurodesis or when
      the fluid had not been drained off previously but there were strong radiological
      indications for a 'trapped lung'. The intervention was considered to be
      contraindicated by the following: dyspnoea that had not been reduced by previous
      pleural punctures performed for relief, dyspnoea caused by many different
      factors, a tendency for haemorrhaging that could not be corrected. The drain used
      was a Pleurx indwelling catheter, a thorax drain that is tunnelled
      subcutaneously, can remain in situ for a long time and offers the patient the
      opportunity to drain off fluid himself at any desired moment. RESULTS: In the
      period September 2003-May 2005, the treatment was considered in 40 patients.
      Ultimately, the catheter was inserted in 25 patients; the clinical deterioration
      of most of the other patients was too quick. Of the group, 33 patients (82%) died
      with a median survival of 70 days. All catheters functioned until they were
      removed or until the patient died. In 3 patients, the drainage procedure was
      complicated by empyema and in 1 patient by haemoptysis. From the total number of
      catheters, 9 were removed while the patient was still alive and in 6 patients,
      spontaneous pleurodesis occurred following 3, 4, 4, 5, 6, and 8 months
      respectively. In general, the patients were able to handle the catheter without
      problems and the symptoms were brought and kept adequately under control.
      CONCLUSION: The Pleurx indwelling pleural catheter was an efficacious treatment
      supplement for patients with malignant pleural effusion, in whom the standard
      pleurodesis was not effective.

PMID- 16901067
TI  - [A man with a classic serious milk-alkali syndrome and a carcinoma of the
      stomach].
AB  - A 42-year-old man was transferred to the Emergency Department after his friends
      had found him unresponsive and confused in his room. He had been experiencing
      upper abdominal complaints for a period of several months. He had taken large
      amounts of a calcium carbonate/magnesium subcarbonate preparation (Rennie) and
      had consumed at least 3 litres of dairy products per day. His behaviour was
      reported as being more and more abnormal during the previous few weeks. On
      admission he was confused and agitated and had involuntary movements of his
      limbs. Laboratory investigation indicated a triple acid base disorder, i.e.
      metabolic alkalosis, respiratory alkalosis and high anion gap metabolic acidosis,
      with severe dehydration. The metabolic alkalosis was caused by the intake of
      large amounts of dairy and antacids: milk-alkali syndrome. The metabolic acidosis
      was the result of hypovolaemia and pre-renal renal failure and the respiratory
      alkalosis was caused by hyperventilation due to the organic psychosyndrome. The
      patient was treated with volume expansion by isotonic saline and the
      administration of potassium and he was sedated with low-dose midazolam, which led
      to a full respiratory compensation of the metabolic alkalosis. A few days
      following admission, both the plasma calcium concentration and renal function
      returned to normal; the acid-base disorder completely normalized and the organic
      psychosyndrome disappeared. On gastroduodenoscopy a gastric ulcer was found;
      biopsies revealed a signet ring cell adenocarcinoma of the stomach.

PMID- 16901068
TI  - [Muckle-Wells syndrome: a rare periodic fever syndrome].
AB  - A 41-year-old patient was referred to our rheumatology ward due to a long history
      of urticaria, joint pain and fever. These symptoms appeared during the evening
      and then resolved during the night. Extensive testing in the past failed to
      provide a diagnosis and treatment with high-dose corticosteroids, methotrexate
      and colchicine was ineffective. Based on clinical criteria, including bilateral
      sensorineural hearing loss, we diagnosed Muckle-Wells syndrome, a rare auto
      inflammatory disease considered one of the hereditary periodic fever syndromes
      and caused by a mutation in the CIAS1 gene. There was a remarkable response to
      anakinra, an interleukin-1 receptor antagonist. The favourable results suggest
      that interleukin-1 plays an important role in the development of this syndrome.

PMID- 16901069
TI  - [A localized reaction to sublingual immunotherapy].
AB  - An otherwise healthy 31-year-old woman with allergic rhinoconjunctivitis
      developed considerable swelling of the floor of her mouth after sublingual
      allergen-specific immunotherapy with the hyposensitization product 'Slit One
      grass pollen'. After discontinuation, complaints disappeared and she was
      successfully put on a regimen of subcutaneous immunotherapy. Despite a lack of
      reports of serious adverse reactions in clinical trials, the Inspectorate of
      Health Care and The Netherlands Pharmacovigilance Centre Lareb received several
      reports of sometimes serious localized reactions to oral and sublingual allergen
      specific immunotherapy. Under-reporting is likely since local reactions are more
      or less expected. Caution should be exercised with allergen treatment, even in
      the case of non-invasive administration.

PMID- 16901070
TI  - [Screening of asymptomatic individuals for coronary disease using CT-calcium
      measurement in the coronary arteries].

PMID- 16901071
TI  - [Brain infarction due to polycythemia as first indication of renal cell
      carcinoma].

PMID- 16901072
TI  - Antiphospholipid syndrome: what's new in understanding antiphospholipid antibody
      related stroke?

PMID- 16901073
TI  - Treatment of refractory polymyositis and dermatomyositis.
AB  - Polymyositis (PM) and dermatomyositis (DM) are autoimmune inflammatory diseases
      that primarily target muscle. Although similar, PM and DM have different
      pathophysiologic mechanisms. Current therapy for PM and DM does not take into
      account these pathophysiologic differences. Recent work has started to define
      outcome measures to apply to future therapeutic trials, which will allow better
      comparison of treatment outcomes. For patients who are unresponsive to standard
      therapy with high dose prednisone supplemented by methotrexate and/or
      azathioprine it is not clear what represents the next best choice for therapy.
      Although there are few controlled studies in the area, there is reason to be
      optimistic for use of intravenous methylprednisolone pulses, intravenous
      gammaglobulin, cyclosporine A, tacrolimus, mycophenolate mofetil, and rituximab
      for nonresponding patients. Better understanding of the underlying
      pathophysiology of PM and DM, as well as carefully performed multicenter clinical
      trials is going to be necessary to make better recommendations in the future.

PMID- 16901074
TI  - Juvenile dermatomyositis update.
AB  - Recent studies involving juvenile dermatomyositis indicate that the majority of
      affected children have symptoms suggestive of infection prior to disease onset,
      damage to skin and muscle each have a distinct pathophysiology, certain urinary
      muscle metabolites may be useful laboratory markers, and methotrexate used as
      first line therapy with corticosteroids is associated with greater height
      velocity and smaller increase in body mass index.

PMID- 16901075
TI  - Differential diagnosis of idiopathic inflammatory myopathies.
AB  - Symmetric proximal muscle weakness has many potential etiologies. An onset over
      weeks to months and elevated serum levels of muscle enzymes point to the
      diagnosis of an idiopathic inflammatory myopathy, including dermatomyositis,
      polymyositis, and inclusion body myositis. However, there is a broad differential
      diagnosis, including certain muscular dystrophies, metabolic myopathies, drug- or
      toxin-induced myotoxicity, neuropathies, and infectious myositides. The
      differentiation is critical for defining appropriate treatment. In addition, an
      alternative diagnosis may explain the lack of response to immunosuppressive
      treatment for some patients with polymyositis. Careful clinical evaluation and
      choice of available diagnostic tests are required to establish the correct
      diagnosis.

PMID- 16901076
TI  - Pathogenesis of idiopathic inflammatory myopathies.
AB  - The idiopathic inflammatory myopathies, myositis, are characterized by a chronic
      course with decreased muscle endurance and by infiltrates of T lymphocytes and
      macrophages in muscle tissue. Treatment with immunosuppressives rarely leads to
      recovery of muscle function, despite abolishment of inflammatory cell infiltrates
      in muscle tissue. Therefore, other mechanisms than immune-mediated muscle fiber
      damage are likely to contribute to the pathogenesis. One such non-immune-mediated
      muscle dysfunction could be caused by a disturbed microcirculation due to
      capillary loss or to phenotypically changed endothelial cells in the capillaries.
      These aberrations may affect the micro-environment of muscle tissue and lead to
      local tissue hypoxia with development of a secondary metabolic myopathy. Another
      possible non-immune-mediated mechanism leading to muscle dysfunction is the newly
      identified endoplasmatic reticulum (ER) stress response in myositis. The ER
      stress response is thought to be a consequence of the up-regulation of major
      histocompatibility complex class I in muscle fibers. These newly identified
      molecular pathways could play a major role in the pathogenesis of myositis and
      could be important targets in the development of new therapies.

PMID- 16901077
TI  - Myositis specific autoantibodies.
AB  - Recent studies have continued to examine the clinical associations of the group
      of autoantibodies that occurs predominantly in patients who have myositis
      (antibodies to aminoacyl-tRNA synthetases, to signal recognition particle [SRP],
      and to the nuclear helicase Mi-2). The anti-synthetase syndrome has been further
      studied, and the value of tacrolimus in treatment of the associated interstitial
      lung disease has been noted. The low frequency of myositis specific
      autoantibodies in non-myositis neuromuscular disorders has been more clearly
      demonstrated. The clinical associations of anti-Mi-2 and anti-SRP were further
      studied, and patients with antibodies without myositis were reported. Evidence
      suggested that ultraviolet light exposure may influence the expression of
      dermatomyositis and anti-Mi-2. A new classification for myositis using overlap
      clinical features and autoantibodies was proposed. A new autoantibody, anti-caDM
      140, was described, associated with clinically amyopathic dermatomyositis and
      interstitial lung disease. The possibility was raised that increased antigen
      expression in regenerating muscle may help to perpetuate the disease. These
      antibodies continue to be the subject of active investigation.

PMID- 16901079
TI  - Innate immunity in triggering and resolution of acute gouty inflammation.
AB  - Gout has long been recognized as a disease of recurrent bouts of acute
      inflammation that undergo self-resolution. This inflammation is triggered by the
      body's response to monosodium urate (MSU) crystals. In this paper, we focus on
      recent studies that describe how interactions of MSU crystals with the components
      of the innate immune system trigger acute gouty inflammation as well as
      mechanisms that are involved in the resolution of this inflammation.
      Specifically, we describe how toll-like receptors mediate the uptake of MSU
      crystals involved in the initiation and resolution of gouty inflammation. We also
      describe recent findings on the role of apoptotic clearance in the resolution of
      gouty inflammation. In addition, how therapies used to treat gout act on the
      innate immune system to inhibit MSU crystal-induced inflammation and promote the
      resolution of inflammation is discussed.

PMID- 16901081
TI  - New developments in clinically relevant mechanisms and treatment of
      hyperuricemia.
AB  - The prevalence of gout has increased markedly in the United States in the past
      two decades, and new treatments for hyperuricemia are being developed. Recent
      molecular identification of urate transporter-1 (URAT1) as the central mediator
      of renal urate reabsorption has provided novel understanding of the pathogenesis
      of hyperuricemia, and the target site for current and possibly future primary
      uricosuric agents. Recent studies have also highlighted uricosuric effects of
      several drugs (losartan, atorvastatin, fenofibrate) that are prescribed for
      primary indications other than hyperuricemia. The niche of these agents in
      current management of hyperuricemia is discussed. We also review the ongoing
      development of recombinant uricase preparations and of novel xanthine oxidase
      inhibitors exemplified by febuxostat. These agents should provide novel options
      for patients with chronic, refractory gout and hyperuricemia, particularly in
      association with allopurinol hypersensitivity and renal insufficiency.

PMID- 16901080
TI  - New developments in the epidemiology and genetics of gout.
AB  - The prevalence of gout appears to be rapidly increasing worldwide and is no
      longer a disorder suffered primarily by over-fed alcohol consumers. Emerging risk
      factors include longevity, metabolic syndrome, and new classes of pharmacologic
      agents. In some ethnic populations, no obvious risk factors can explain the high
      incidence of hyperuricemia and gout, suggesting a genetic liability. Studies to
      identify genes associated with gout have included families with defects in purine
      metabolism, as well as families in whom the occurrence of gout is secondary to
      renal disorders such as juvenile hyperuricemic nephropathy and medullary cystic
      kidney disease. Case-control studies of isolated aboriginal cohorts suffering
      from primary gout have revealed several chromosomal loci that may harbor genes
      that are important to the development and/or progression of gout.

PMID- 16901082
TI  - The advanced imaging of gouty tophi.
AB  - Gout is a metabolic disorder in which there is hyperuricemia caused by an
      increase in production or a decrease in excretion of uric acid. Long-lasting
      hyperuricemia causes the deposition of monosodium urate crystals in the joints
      and soft tissues, triggering gouty arthritis and, if not properly treated, the
      formation of gouty tophi. The diagnosis of gout is usually based on clinical
      presentation and laboratory examinations, long before any abnormality can be
      demonstrated with imaging. Radiography is the primary imaging modality used in
      the initial evaluation of gouty arthritis. Ultrasonography, CT, MRI, and nuclear
      medicine are seldom necessary. Occasionally a tophus has an unusual presentation
      and simulates neoplasm or infection prompting the utilization of cross-sectional
      imaging for further evaluation and surgical planning. Cross-sectional imaging is
      also used in areas that are difficult to visualize on radiographs such as spine,
      sacroiliac joints, and soft tissues.

PMID- 16901084
TI  - Qualitatively predicting acetylation and methylation areas in DNA sequences.
AB  - Eukaryotic genomes are packaged by the wrapping of DNA around histone octamers to
      form nucleosomes. Nucleosome occupancy, acetylation, and methylation, which have
      a major impact on all nuclear processes involving DNA, have been recently mapped
      across the yeast genome using chromatin immunoprecipitation and DNA microarrays.
      However, this experimental protocol is laborious and expensive. Moreover,
      experimental methods often produce noisy results. In this paper, we introduce a
      computational approach to the qualitative prediction of nucleosome occupancy,
      acetylation, and methylation areas in DNA sequences. Our method uses support
      vector machines to discriminate between DNA areas with high and low relative
      occupancy, acetylation, or methylation, and rank k-gram features based on their
      support for these DNA modifications. Experimental results on the yeast genome
      reveal genetic area preferences of nucleosome occupancy, acetylation, and
      methylation that are consistent with previous studies. Supplementary files are
      available from http://www.jaist.ac.jp/~tran/nucleosome/.

PMID- 16901083
TI  - Clinical manifestations and pathogenesis of hydroxyapatite crystal deposition in
      juvenile dermatomyositis.
AB  - Pathologic deposition of mineral in the form of bone-like hydroxyapatite is a
      frequent occurrence in juvenile dermatomyositis (JDM) and other connective tissue
      diseases. Although the sizes of the mineral crystals in JDM are similar to those
      in bone, there is much more mineral in the deposits than there is in bone. Bone
      matrix proteins also accumulate associated with the deposits. The reasons for the
      formation of these deposits are not known. It is our hypothesis that persistent
      inflammation is a component of JDM and other hydroxyapatite deposition diseases.
      Other contributing factors are genetic, environmental, and physical chemical.
      This paper discusses the influence of inflammation on the deposition of
      hydroxyapatite, with emphasis on the clinical and environmental factors that may
      facilitate the formation of calcific deposits in JDM.

PMID- 16901085
TI  - Knowledge-based prediction of DNA atomic structure from nucleic sequence.
AB  - A simple knowledge-based method for DNA atomic structure prediction from nucleic
      sequence is presented. We used free B-DNA crystal structures to estimate the
      distribution of trinucleotide base pairs and tetranucleotide base-pair steps
      conformational coordinates. We used these distributions as a basis to predict the
      3D position of the non-hydrogen atoms of the nucleic bases of any arbitrary DNA
      sequence of any length. The only constraint imposed was that the structure is a B
      DNA one with Watson-Crick complementary base pairs. The method was tested on not
      seen DNA structures with sequence lengths varying from 6bp to 12bp. The obtained
      predictions have RMSE around 0.5 A for the translational conformational
      coordinates, and around 5 degrees for the rotational. For the estimation of the
      nucleic base non-hydrogen atom coordinates the RMSE is around 1.1 A. The
      knowledge-based method outperformed a technique based on genetic algorithms in
      the prediction of B-DNA structures.

PMID- 16901086
TI  - Automatic drawing of biological networks using cross cost and subcomponent data.
AB  - Automatic graph drawing function for biopathways is indispensable for biopathway
      databases and softwares. This paper proposes a new grid-based algorithm for
      biopathway layout that considers (a) edge-edge crossing, (b) node-edge crossing,
      (c) distance measures between nodes, as its costs, and (d) subcellular
      localization information from Gene Ontology, as its constraints. For this
      algorithm, we newly define cost functions, devise an efficient method for
      computing the costs (a)-(c) by employing a matrix representing the difference
      between two layouts, and take a steepest descent method for searching locally
      optimal solutions and multi-step layout method for finding better solutions. We
      implemented this algorithm on Cell Illustrator which is a biopathway modeling and
      simulation software. The algorithm is applied to a signal transduction pathway of
      apoptosis induced by fas ligand. We compare our layout with that of the grid
      based algorithm by Li and Kurata (Bioinformatics 21 (9):2036-2042, 2005). The
      result shows that our algorithm reduces edge-edge crossings and node-edge
      crossings, and solves the ''isolated island problem'', that is, despite the
      intension, some groups of nodes are apart from other nodes in the layout. As a
      result, the biological understandability of the layout is fairly improved.

PMID- 16901087
TI  - Supporting the curation of biological databases with reusable text mining.
AB  - Curators of biological databases transfer knowledge from scientific publications,
      a laborious and expensive manual process. Machine learning algorithms can reduce
      the workload of curators by filtering relevant biomedical literature, though
      their widespread adoption will depend on the availability of intuitive tools that
      can be configured for a variety of tasks. We propose a new method for supporting
      curators by means of document categorization, and describe the architecture of a
      curator-oriented tool implementing this method using techniques that require no
      computational linguistic or programming expertise. To demonstrate the feasibility
      of this approach, we prototyped an application of this method to support a real
      curation task: identifying PubMed abstracts that contain allergen cross
      reactivity information. We tested the performance of two different classifier
      algorithms (CART and ANN), applied to both composite and single-word features,
      using several feature scoring functions. Both classifiers exceeded our
      performance targets, the ANN classifier yielding the best results. These results
      show that the method we propose can deliver the level of performance needed to
      assist database curation.

PMID- 16901088
TI  - Reconstruction of phylogenetic relationships from metabolic pathways based on the
      enzyme hierarchy and the gene ontology.
AB  - There has been much interest in the structural comparison and alignment of
      metabolic pathways. Several techniques have been conceived to assess the
      similarity of metabolic pathways of different organisms. In this paper, we show
      that the combination of a new heuristic algorithm for the comparison of metabolic
      pathways together with any of three enzyme similarity measures (hierarchical,
      information content, and gene ontology) can be used to derive a metabolic pathway
      similarity measure that is suitable for reconstructing phylogenetic relationships
      from metabolic pathways. Experimental results on the Glycolysis pathway of 73
      organisms representing the three domains of life show that our method outperforms
      previous techniques.

PMID- 16901089
TI  - Mass identification of chloroplast proteins of endosymbiont origin by
      phylogenetic profiling based on organism-optimized homologous protein groups.
AB  - Chloroplasts originate from ancient cyanobacteria-like endosymbiont. Several tens
      of chloroplast proteins are encoded by the chloroplast genome, while more than
      hundreds are encoded by the nuclear genome in plants and algae, but the exact
      number and identity of nuclear-encoded chloroplast proteins are still unknown. We
      describe here attempts to identify a large number of unidentified chloroplast
      proteins of endosymbiont origin (CPRENDOs). Our strategy consists of whole genome
      protein clustering by the homolog group method, which is optimized for organism
      number, and phylogenetic profiling that extract groups conserved in cyanobacteria
      and photosynthetic eukaryotes. An initial minimal set of CPRENDOs was predicted
      without targeting prediction and experimentally validated.

PMID- 16901090
TI  - Strategies for genome reduction in microbial genomes.
AB  - Niche dependent differential gene loss and overlapping genes have been proposed
      as means of achieving genome reduction by retaining indispensable genes and
      compressing maximum amount of information in available sequence space. Herein, we
      analyzed the differential gene loss and overlapping genes in bacterial genomes
      with different lifestyles. Our results clearly suggest that gene loss and
      overlapping genes could be a result of evolutionary pressure to minimize genome
      size. Comparative analysis of the genomes shows that the genomes display marked
      similarities in patterns of protein length and frequency. It is clear from our
      analysis that habitat is a major factor contributing to genome reduction. These
      comparisons increase our knowledge of the forces that drive the extreme
      specialization of the bacteria and its association to the host.

PMID- 16901091
TI  - Reassembly and interfacing neural models registered on biological model
      databases.
AB  - The importance of modeling and simulation of biological process is growing for
      further understanding of living systems at all scales from molecular to cellular,
      organic, and individuals. In the field of neuroscience, there are so called
      platform simulators, the de-facto standard neural simulators. More than a hundred
      neural models are registered on the model database. These models are executable
      in corresponding simulation environments. But usability of the registered models
      is not sufficient. In order to make use of the model, the users have to identify
      the input, output and internal state variables and parameters of the models. The
      roles and units of each variable and parameter are not explicitly defined in the
      model files. These are suggested implicitly in the papers where the simulation
      results are demonstrated. In this study, we propose a novel method of reassembly
      and interfacing models registered on biological model database. The method was
      applied to the neural models registered on one of the typical biological model
      database, ModelDB. The results are described in detail with the hippocampal
      pyramidal neuron model. The model is executable in NEURON simulator environment,
      which demonstrates that somatic EPSP amplitude is independent of synapse
      location. Input and output parameters and variables were identified successfully,
      and the results of the simulation were recorded in the organized form with
      annotations.

PMID- 16901092
TI  - Objective measurement of spindle orientation in early Caenorhabditis elegans
      embryo.
AB  - The spindle orientation is a crucial piece of information to understand the
      development of embryo. The spindle forms during cell division and the cell
      divides along the spindle axis. Spindle orientation was measured in many
      different mutant embryos of Caenrohabditis elegans. However, the objectivity and
      the productivity of these measurements were low because these measurements were
      made manually. Here we present a system that automates the measurement of the
      spindle orientation in C. elegans embryo. Automation increases the objectivity
      and productivity of the measurement. We confirmed the applicability of the system
      by applying it to spindles during the second divisions in wild-type and mutant C.
      elegans embryos.

PMID- 16901093
TI  - Evolution from possible primitive tRNA-viroids to early poly-tRNA-derived mRNAs:
      a new approach from the poly-tRNA theory.
AB  - Poly-tRNA theory have revealed that the tRNA gene-clusters in the Bacillus
      subtilis trrnD- and rrnB-operons are relics of early peptide-synthesizing RNA
      apparatus. The trrnD-type and rrnB-type poly-tRNA models were re-analyzed by
      using recent databases. The results elucidated that the 16 amino acid (aa)-trrnD-
      and the 21 aa-rrnB-peptides (whose aa sequences are in the order of aa
      specificities of tRNAs in the respective tRNA cluster) are really relics of
      earliest peptides encoded by most primitive mRNAs, trrnD-mRNA and rrnB-mRNA,
      which are homologous to tRNA(Gly) and tRNA(His), respectively. Genes encoding
      various protein superfamilies (including pgtB protein, glycyl-tRNA synthetase
      alpha, C-type lectin, F1-ATP-synthase gamma, etc) were concluded to have derived
      from tRNA(Gly)-tRNA(Cys)-tRNA(Leu) region (including trrnD-mRNA region) in the
      trrnD-poly-tRNA. Genes for another group of protein superfamilies (including
      adenylate kinase, glyceraldehyde-3-phosphate dehydrogenase, helix-turn-helix DNA
      binding domains, etc.) were found to have derived rrnB-mRNA, which is most
      plausibly homologous to a region containing the tRNA(His) of the rrnB-poly-tRNA.
      Thus Proto-tRNA((Gly)) reconstructed from tRNA(Gly) and other tRNAs strongly
      suggested that proto-tRNA was most plausibly a viroid-like possibly self
      cleavable replicable ribozyme possessing a possible hammerhead-like structure.

PMID- 16901094
TI  - A study of fragment-based protein structure prediction: biased fragment
      replacement for searching low-energy conformation.
AB  - A novel fragment replacement strategy for the fragment-based protein structure
      prediction is proposed. Despite the recent advance of de novo prediction of
      protein tertiary structure, intricate protein topologies still exist at
      unsatisfactory prediction quality. Although this difficulty is in part due to the
      accuracy of energy functions, it also relates to the search ability of sampling
      methods. To enhance the global optimization method that finds low-energy
      conformations, this study tests a biased sampling approach. The proposed approach
      is inspired by the fact that local structures of a protein have geometrical
      rigidity and flexibility. For capturing the pivotal local structures to generate
      various topologies, this approach first measures the energetic fluctuation of
      target fragments on dihedral angles of a protein, and then the quantity is
      converted to probability used by probabilistic selection of fragment replacement.
      Due to the requirement of the dihedral angles, a Genetic Algorithm implements the
      proposed idea, and experimental results show that the GA is capable of providing
      the dihedral angles as template-like proteins. The results suggest that the
      proposed approach can reach low-energy conformations with comparable prediction
      quality to that of an existing method. Interestingly, the low-energy states were
      associated with the frequent replacement of fragments in natively-coil regions.
      However, unfavorable compactification of the predicted models was observed. All
      experimental data are available at http://www.proteinsilico.org/PRO/.

PMID- 16901095
TI  - Comparison of protein structures by multi-objective optimization.
AB  - We propose a novel method for solving the structure comparison problem for
      proteins, based on a decomposition technique. We define the structure alignment
      as a multi-objective optimization problem with both discrete and continuous
      variables, i.e., maximizing the number of aligned atoms and minimizing their root
      mean square distance. By controlling a single distance-related parameter,
      theoretically we can obtain a variety of optimal alignments corresponding to
      different optimal matching patterns, i.e., from a large matching portion to a
      small portion. The number of variables in our algorithm increases with the number
      of atoms of protein pairs in almost a linear manner. The software is available
      upon request, or from http://zhangroup.aporc.org/bioinfo/samo/.

PMID- 16901096
TI  - Statistical evaluation of a bottom-up clustering for single particle molecular
      images.
AB  - We examined the statistical performance of clustering single particle molecular
      images by bottom-up clustering, a hierarchical algorithm, using simulated protein
      images with a low signal-to-noise ratio. Using covariance for the measure of
      similarity together with the iterative alignment, our method was found to be
      fairly robust against noise. Clustering tests of four known protein structures
      were performed at three levels of noise and with three levels of smoothing. A
      significant effect of smoothing was confirmed in our results for images with
      noise suggesting an effective degree of smoothing depending on the noise and
      structural features of the target molecule. The consistency of clustering results
      was evaluated by the average solid angle of projection, and the precision of our
      clustering results was checked by the average image correlation between the
      obtained cluster image and the true projection. Once image features are extracted
      appropriately, the average solid angle also represents the degree of clustering
      precision.

PMID- 16901097
TI  - Inter-species validation for domain combination based protein-protein interaction
      prediction method.
AB  - Domain Combination based Protein-Protein Interaction Prediction (DCPPIP) method
      is revealed to show outstanding prediction accuracy in Yeast proteins. However,
      it is not yet apparent whether the method is still valid and can achieve
      comparable prediction accuracy for the proteins in other species. In this paper,
      we report the validation results of applying the DCPPIP method for Fly and Human
      proteins. We also report the results of inter-species validation, in which
      protein interaction and domain data of other species are used as learning set.
      10,351 interacting protein pairs are used for the validation for Fly, 2,345
      protein pairs for Human. 80% of the data are used as learning sets and 20% are
      reserved as test sets. High prediction accuracies (Fly: sensitivity approximately
      77%, specificity approximately 92%, Human: sensitivity approximately 96%,
      specificity approximately 95%) are achieved in both Fly and Human cases.
      Interactions of proteins in Human, Mouse, H. pylori, E. coli, and C. elegans are
      predicted and validated using the protein interaction and domain data in Yeast,
      Fly, and the combination of Yeast and Fly respectively. Again, good prediction
      accuracy is achieved when the test protein pair has common domains with the
      proteins in a learning set of proteins. A notion of Domain Overlapping Rate (DOR)
      among species is newly developed in this paper and the correlation between DOR
      and prediction accuracy is examined. According to out test results, there exists
      fairly obvious correlation between DOR and prediction accuracy.

PMID- 16901099
TI  - A fast protein-protein docking algorithm using series expansion in terms of
      spherical basis functions.
AB  - We describe a fast protein-protein docking algorithm using a series expansion in
      terms of newly designed bases to efficiently search the entire six-dimensional
      conformational space of rigid body molecules. This algorithm is an ab initio
      docking algorithm designed to list candidates of putative conformations from a
      global conformational space for unbound docking. In our algorithm, a scoring
      function is constructed from terms that are the inner products of two scalar
      fields expressing individual molecules. The mapping from a molecule to a scalar
      field can be arbitrarily defined to express an energy term. Since this scoring
      scheme has the same expressiveness as that of a method using a fast Fourier
      transform (FFT), it has the flexibility to introduce various physicochemical
      energies. Currently, we are using scalar fields that approximate desolvation free
      energy and steric hindrance energy. Fast calculation of the scoring function for
      each conformation of the six-dimensional search space is realized by expansion of
      the fields in terms of basis functions which are combinations of spherical
      harmonics and modified Legendre polynomials, and the use of only low-order terms,
      which carry most of the information on the scalar field. We have implemented this
      algorithm and evaluated the computation time and precision by using actual
      protein structure data of complexes and their monomers. This paper presents the
      results for six unbound cases and in all the cases we obtained at least one
      conformation close to the native structures (interface RMSD < 3.0 A) within the
      top 1000 candidates with about 40 seconds of computation time using a single
      Pentium4 2.4 GHz CPU.

PMID- 16901098
TI  - A graph theoretical approach for analysis of protein flexibility change at
      protein complex formation.
AB  - Hitherto analyses of protein complexes are frequently confined to the changes in
      the interface of the protein subunits undergoing interaction, while the holistic
      picture of the protein monomers' structure transformation, or the pervasive
      rigidity adopted by the newly formed complex are most often than not improperly
      evaluated in spite of the multiple and deep insights that they can yield about
      the interaction process itself at the molecular level, or at the higher level of
      genomic functional analyses for which relevant systems biological information can
      be obtained. To address this aspect of protein-protein interaction we propose in
      this work a newly developed algorithm that is based on graph theoretical
      instances and makes possible the evaluation of the changes in the flexibility of
      the interacting molecules and the rigidity adopted at complex formation. Since
      one can also figure out the opposite process, i.e. that in which the complex
      decomposes into its constituent subunits, each of which may accomplish another
      vital role in the organism, the methodology proposed here is also able to address
      such problem. The algorithm we propose performs a rigidity and/or flexibility
      evaluation of every node (atom) on the network constituted by the entire set of
      intra and inter-molecular inter-atomic interactions. Comparison of flexible or
      rigid molecular regions or domains within the complex with those in the
      respective isolated monomers leads to quantification of the loss (or gain) in the
      number of degrees of freedom at complex formation and their effects on protein
      complex formation mechanisms. This index is also valuable in the identification
      of collective motions within the protein that may play a critical role in the
      process of complex formation, and the influences they may have in the behavior
      and function of the complex (as well as the subunits constituting it) within the
      organism. Furthermore, the methodology, embedded in protein docking algorithms
      allows the development of a framework for categorizing and ranking decoys output
      by broadly used grid scoring type algorithms, one of which is the system for
      protein-protein interaction system MIAX that has been under continuous
      development in recent years.

PMID- 16901100
TI  - Viewing the proteome from oligopeptides and prediction of protein function.
AB  - Our research activity of making the lexicon of relatively short oligopeptides has
      been one of the first steps to view the world of proteome from the perspective of
      oligopeptides. We propose a new method for the prediction of protein function,
      especially GeneOntology terms (GO terms), based on statistical characteristics of
      oligopeptides as an application of the lexicon. In the lexicon, a known function
      of a protein is inherited to its oligopeptides, and the correspondence between
      oligopeptides and the function is calculated in the whole proteins. In our
      method, unknown functions of proteins are predicted by means of the
      correspondence automatically. We measured the prediction performance using the
      28,520 whole human proteins registered in RefSeq for several GO terms by recall
      precision graphs. The GO terms include 'membrane', 'nucleus', 'ATP binding',
      'hydorolase activity', 'GTP binding', 'intracellular signaling cascade' and
      'ubiquitin cycle'. In most cases, it scores 70% recall with 80% precision. The
      prediction for ATP binding and GTP binding results in quite high performance: it
      scores 80% recall with 80% precision. Even in the worst case (ubiquitin cycle),
      it scores 62.6% recall with 80% precision. These results suggest that the
      proposed method is quite efficient for predicting GO terms.

PMID- 16901101
TI  - Mass distributed clustering: a new algorithm for repeated measurements in gene
      expression data.
AB  - The availability of whole-genome sequence data and high-throughput techniques
      such as DNA microarray enable researchers to monitor the alteration of gene
      expression by a certain organ or tissue in a comprehensive manner. The quantity
      of gene expression data can be greater than 30,000 genes per one measurement,
      making data clustering methods for analysis essential. Biologists usually design
      experimental protocols so that statistical significance can be evaluated; often,
      they conduct experiments in triplicate to generate a mean and standard deviation.
      Existing clustering methods usually use these mean or median values, rather than
      the original data, and take significance into account by omitting data showing
      large standard deviations, which eliminates potentially useful information. We
      propose a clustering method that uses each of the triplicate data sets as a
      probability distribution function instead of pooling data points into a median or
      mean. This method permits truly unsupervised clustering of the data from DNA
      microarrays.

PMID- 16901102
TI  - Diagnosis of early relapse in ovarian cancer using serum proteomic profiling.
AB  - Surface-enhanced laser desorption/ionization time-of-flight (SELDI-TOF) mass
      spectrometry data has been increasingly analyzed for identifying biomarkers to
      help early detection of the disease. Ovarian cancer commonly recurs at the rate
      of 75% within a few months or several years later after standard treatment. Since
      recurrent ovarian cancer is relatively difficult to be diagnosed and small tumors
      generally respond better to treatment, new methods for the detection of early
      relapse in ovarian cancer are urgently needed. Here, we propose a new algorithm
      SVM-MB/RFE (SVM-Markov Blanket/Recursive Feature Elimination) based on SVM-RFE,
      which identifies biomarkers for predicting the early recurrence of ovarian
      cancer. In this approach, we first apply t-test for feature pruning and then
      binning using 5-fold cross validation. Finally, 58 peaks are obtained from 27,000
      of the raw data. Such dramatically reduced features relax the computational
      burden in the next step of our algorithm. We compare the performance of three
      feature selection algorithms and demonstrate that SVM-MB/RFE outperforms other
      methods.

PMID- 16901103
TI  - Reverse engineering genetic networks using evolutionary computation.
AB  - This paper proposes an improved evolutionary method for constructing the
      underlying network structure and inferring effective kinetic parameters from the
      time series data of gene expression using decoupled S-system formalism. We
      employed Trigonometric Differential Evolution (TDE) as the optimization engine of
      our algorithm for capturing the dynamics in gene expression data. A more
      effective fitness function for attaining the sparse structure, which is the
      hallmark of biological networks, has been applied. Experiments on artificial
      genetic network show the power of the algorithm in constructing the network
      structure and predicting the regulatory parameters. The method is used to
      evaluate interactions between genes in the SOS signaling pathway in Escherichia
      coli using gene expression data.

PMID- 16901104
TI  - Toward integration of systems biology formalism: the gene regulatory networks
      case.
AB  - We consider the problem of integrating different systems biology formalisms,
      namely, the process calculi based formalism, the modeling approach based on
      systems of differential equations, and the one relying on automata-like
      descriptions (and model checking). Specifically, we define automatic procedures
      for translating stochastic pi-calculus descriptions of gene regulatory networks
      to S-systems differential equations. Tools for extracting and reasoning on
      (approximate) solutions of S-systems have been recently developed in the
      literature, and can be exploited to establish a link with automata-based systems
      biology and model checking techniques.

PMID- 16901105
TI  - Reconstruction of gene regulatory networks under the finite state linear model.
AB  - We study the Finite State Linear Model (FSLM) for modelling gene regulatory
      networks proposed by A. Brazma and T. Schlitt in [4]. The model incorporates
      biologically intuitive gene regulatory mechanism similar to that in Boolean
      networks, and can describe also the continuous changes in protein levels. We
      consider several theoretical properties of this model; in particular we show that
      the problem whether a particular gene will reach an active state is
      algorithmically unsolvable. This imposes some practical difficulties in
      simulation and reverse engineering of FSLM networks. Nevertheless, our simulation
      experiments show that sufficiently many of FSLM networks exhibit a regular
      behaviour and that the model is still quite adequate to describe biological
      reality. We also propose a comparatively efficient O(2(K)n(K+1)M(2K)m log m) time
      algorithm for reconstruction of FSLM networks from experimental data. Experiments
      on reconstruction of random networks are performed to estimate the running time
      of the algorithm in practice, as well as the number of measurements needed for
      successful network reconstruction.

PMID- 16901106
TI  - A space-efficient algorithm for the constrained pairwise sequence alignment
      problem.
AB  - The constrained pairwise sequence alignment (CPSA) problem aims to align two
      given sequences by aligning their similar subsequences in the same region under
      the guidance of a given pattern (constraint). Let the lengths of the sequences be
      m, and n where n <or= m, and let r <or= n be the length of the given pattern. The
      optimum constrained pairwise alignment score can be computed using O(rn) space by
      a naive dynamic programming solution. If an optimal alignment path is desired
      then the space requirement of the naive dynamic programming algorithm is O(rnm).
      There is a divide-and-conquer algorithm that reduces the memory requirement of
      finding an optimal alignment for the CPSA problem to O(rn). In this paper, we
      present a space-efficient CPSA algorithm that returns an optimal alignment. Our
      analysis on real protein sequences suggests that our algorithm requires only O(n)
      space in practice. This algorithm is not only space efficient but also very fast.
      A generalization of the CPSA problem for multiple sequences is called the
      constrained multiple sequence alignment (CMSA) problem. Our CPSA algorithm also
      improves the space requirement of progressive CMSA algorithms that use solutions
      of CPSA problems.

PMID- 16901107
TI  - Prediction of functional modules based on gene distributions in microbial
      genomes.
AB  - We present a computational method for prediction of functional modules that can
      be directly applied to the newly sequenced microbial genomes for predicting gene
      functions and the component genes of biological pathways. We first quantify the
      functional relatedness among genes based on their distribution (i.e., their
      existences and orders) across multiple microbial genomes, and obtain a gene
      network in which every pair of genes is associated with a score representing
      their functional relatedness. We then apply a threshold-based clustering
      algorithm to this gene network, and obtain modules for each of which the number
      of genes is bounded from above by a pre-specified value and the component genes
      are more strongly functionally related to each other than genes across the
      predicted modules. Particularly, when the module size is bounded by 130, we
      obtain 167 functional modules covering 813 genes for Escherichia coli K12, and
      138 functional modules covering 731 genes for Bacillus subtilis subsp. subtilis
      str. 168. We have used the gene ontology (GO) information to assess the
      prediction results. The GO similarities among the genes of the same functional
      module are compared with the GO similarities among the genes that are randomly
      clustered together. This comparison reveals that our predicted functional modules
      are statistically and biologically significant, and the genes of the same
      functional module share more commonality in terms of biological process than in
      terms of molecular function or cellular component. We have also examined the
      predicted functional modules that are common to both Escherichia coli K12 and
      Bacillus subtilis subsp. subtilis str. 168, and provide explanations for some
      functional modules.

PMID- 16901108
TI  - Interaction graph mining for protein complexes using local clique merging.
AB  - While recent technological advances have made available large datasets of
      experimentally-detected pairwise protein-protein interactions, there is still a
      lack of experimentally-determined protein complex data. To make up for this lack
      of protein complex data, we explore the mining of existing protein interaction
      graphs for protein complexes. This paper proposes a novel graph mining algorithm
      to detect the dense neighborhoods (highly connected regions) in an interaction
      graph which may correspond to protein complexes. Our algorithm first locates
      local cliques for each graph vertex (protein) and then merge the detected local
      cliques according to their affinity to form maximal dense regions. We present
      experimental results with yeast protein interaction data to demonstrate the
      effectiveness of our proposed method. Compared with other existing techniques,
      our predicted complexes can match or overlap significantly better with the known
      protein complexes in the MIPS benchmark database. Novel protein complexes were
      also predicted to help biologists in their search for new protein complexes.

PMID- 16901109
TI  - Topology of mammalian transcription networks.
AB  - We present a first attempt to evaluate the generic topological principles
      underlying the mammalian transcriptional regulatory networks. Transcription
      networks, TN, studied here are represented as graphs where vertices are genes
      coding for transcription factors and edges are causal links between the genes,
      each edge combining both gene expression and trans-regulation events. Two
      transcription networks were retrieved from the TRANSPATH database: The first one,
      TN_RN, is a 'complete' transcription network referred to as a reference network.
      The second one, TN_p53, displays a particular transcriptional sub-network
      centered at p53 gene. We found these networks to be fundamentally non-random and
      inhomogeneous. Their topology follows a power-law degree distribution and is best
      described by the scale-free model. Shortest-path-length distribution and the
      average clustering coefficient indicate a small-world feature of these networks.
      The networks show the dependence of the clustering coefficient on the degree of a
      vertex, thereby indicating the presence of hierarchical modularity. Clear
      positive correlation between the values of betweenness and the degree of vertices
      has been observed in both networks. The top list of genes displaying high degree
      and high betweennes, such as p53, c-fos, c-jun and c-myc, is enriched with genes
      that are known as having tumor-suppressor or proto-oncogene properties, which
      supports the biological significance of the identified key topological elements.

PMID- 16901110
TI  - Enzymatic resolution, desymmetrization, and dynamic kinetic asymmetric
      transformation of 1,3-cycloalkanediols.
AB  - An efficient desymmetrization of cis-1,3-cyclohexanediol to (1S,3R)-3-(acetoxy)-1
      cyclohexanol ((R,S)-2a) was performed via Candida antarctica lipase B (CALB)
      catalyzed transesterification, in high yield (up to 93%) and excellent
      enantioselectivity (ee's up to >99.5%). (R,R)-Diacetate ((R,R)-3a) was obtained
      in a DYKAT process at room temperature from (1S,3R)-3-acetoxy-1-cyclohexanol
      ((R,S)-2a), in a high trans/cis ratio (91:9) and in excellent enantioselectivity
      of >99%. Metal- and enzyme-catalyzed dynamic transformation of cis/trans-1,3
      cyclohexanediol using PS-C gave a high diastereoselectivity for cis-diacetate
      (cis/trans = 97:3). The (1R,3S)-3-acetoxy-1-cyclohexanol (ent-(R,S)-2a) was
      obtained from cis-diacetate by CALB-catalyzed hydrolysis in an excellent yield
      (97%) and selectivity (>99% ee). By deuterium labeling it was shown that
      intramolecular acyl migration does not occur in the transformation of cis
      monoacetate to the cis-diacetate.

PMID- 16901111
TI  - Total carbo-mer of benzene, its carbo-trannulene form, and the zigzag nanotube
      thereof.
AB  - The total carbo-mer of benzene, hexaethynyl carbo-benzene C30H6, has been
      calculated at the B3PW91/6-31G** level. Its geometrical and magnetic
      characteristics are compared with those of the C18H6 partial carbo-mers,
      unsubstituted carbo-benzene, and hexaethynylbenzene. The carbo-[6]trannulene
      isomer is found to exist as a minimum on the singlet spin state potential energy
      surface (PES) and is 65.6 kcal.mol(-1) higher in energy than hexaethynyl-carbo
      benzene. In the former, a strong cyclic electron delocalization is evidenced from
      the root-mean-square deviation (rms) of the ring bond lengths and the NICS value
      computed at the centroid of the trannulene ring. As an alternative to the
      graphene sheet wrapping process traditionally used to illustrate the construction
      of carbon nanotubes, a dehydrocoupling-stacking process is invoked for the
      construction of zigzag nanotubes from trannulene bricks. The process is applied
      to the carbo-[6]trannulene brick to generate a novel type of acetylene-expanded
      carbon nanotube, which is a polymer of primitive C60 segments. A C60H6 carbo
      meric equivalent of a cyclacene belt is first considered. Two such segments are
      then formally dehydrocoupled to generate a cylindrical (C60)2H6 molecule, the
      central part of which is assumed to be a relevant model for the infinite
      nanotube. Axial and sectional electron delocalization inside the tube models is
      discussed on the basis of bond length analysis, NICS values, pi MO analysis, and
      singlet-triplet state energy gap. The capping of the C120 cyclinder is finally
      addressed by use of carbo-[3]radialenic units.

PMID- 16901112
TI  - Electronic and hydrogen bonding effects on the chain-breaking activity of sulfur
      containing phenolic antioxidants.
AB  - A kinetic and thermodynamic investigation of phenols para-substituted with thiyl
      (SR), sulfinyl (SOR), and sulfonyl (SO(2)R) groups and ortho-substituted with
      thiyl groups is reported. The effect of the sulfur substituents on the O-H bond
      dissociation enthalpy values, BDE(O-H), was measured by means of the EPR radical
      equilibration technique and the reactivity toward peroxyl radicals, k(inh), of
      these phenolic antioxidants was determined by inhibited autoxidation studies. An
      inverse correlation between these two parameters was found. A p-SMe substituent
      decreased the BDE(O-H) value to a lesser extent than a p-OMe group (-3.6 vs -4.4
      kcal/mol), whereas the effect of the same groups in an ortho position showed an
      opposite trend (-0.85 vs -0.2 kcal/mol). The latter result is explained in terms
      of the different strength of the intramolecular hydrogen bond between the OH
      proton and the sulfur or oxygen substituents in ortho derivatives. ESI-MS
      analysis of the products formed by reacting the sulfides with peroxyl radicals
      from the azoinitiator AIBN revealed the formation of a complex mixture of
      products, which may play an important role in determining the overall antioxidant
      activity of the parent compounds.

PMID- 16901114
TI  - Kinetics and mechanism of the addition of nucleophiles to alpha,beta-unsaturated
      thiol esters.
AB  - Compounds containing the UV-absorbing chromophores p-methoxycinnamate, p
      methoxycinnamide, or anthranilate and an alpha,beta- or alpha,beta,gamma,delta
      unsaturated thiol ester (crotonyl or sorboyl) have been prepared. These compounds
      are subject to nucleophilic attack at the C=C conjugated to the thiol ester
      carbonyl group. The kinetics of the reactions of these thiol esters with N-acetyl
      l-cysteine (NAC), N-acetylcysteamine, and N(2)-acetyl-L-lysine (NAL) have been
      studied, and the thiol addition products have been identified. The reaction rates
      increased at higher pH, and the reaction of NAC thiolate with a crotonyl thiol
      ester in 1:1 (v/v) acetonitrile/aqueous HEPES exhibited buffer catalysis as a
      result of protonation of the enolate intermediate. At the same concentration, NAC
      underwent approximately 300-fold more reaction than NAL with a crotonyl thiol
      ester at pH 9.8. Additionally, a crotonyl thiol ester was found to be 7.9 times
      more reactive than a sorboyl thiol ester toward NAC addition. These unsaturated
      thiol esters may serve as a means of covalently binding UVA and UVB sunscreens to
      the outer layer of skin to provide long-lasting protection.

PMID- 16901113
TI  - Investigations of metal-coordinated peptides as supramolecular synthons.
AB  - This article describes the synthesis and controlled assembly of four model
      biological-hybrid scaffolds via coordination of a metal complex to four new
      tripeptides. Each model tripeptide investigated has either a central pyridyl
      glycyl or a pyridyl alanyl residue between two terminally protected glycines. All
      tripeptides were coordinated to their complementary recognition unit, a p-methoxy
      SCS-Pd pincer complex. The assembly events were fully characterized and
      investigated by 1H NMR, ES-MS, and isothermal titration calorimetry (ITC) to
      elucidate how the substitution and spatial distance of the pyridyl moiety to the
      peptide backbone affects the metal coordination. Using these characterization
      techniques, we have shown that the metal-coordination events in all cases are
      fast and quantitative and that the peptide backbones do not interfere with the
      self-assembly. The ITC analyses showed that the 4-pyridyl tripeptides are the
      tightest binding ligands toward the palladated pincer complexes with the alanyl
      derivative being the strongest overall, demonstrating the superiority of the 4
      pyridyl peptides over their 3-pyridyl analogues. The measured association
      constants are comparable to other pincer-pyridine systems in DMSO suggesting that
      the controlled coordination of the metalated pincer/pyridine interaction is an
      interesting biological synthon and will allow for the future development of
      important noncovalent peptide-based hybrid materials.

PMID- 16901115
TI  - Solid-phase synthesis and configurational reassigment of callipeltin E.
      Implications for the structures of callipeltins A and B.
AB  - Two possible isomers of the natural product callipeltin E (1, 5) were synthesized
      by using an Fmoc-based solid-phase strategy in 7 steps, in 20% and 26% overall
      yields, respectively. The (1)H NMR spectrum of synthetic 5 correlated closely
      with that of the natural product, whereas that of 1 did not, providing
      confirmation of the configurational reassignment of the N-terminal residue of
      callipeltin E as D-allothreonine. This result strongly implies that the
      corresponding residue in the closely related cyclic depsipeptides callipeltins A
      and B should also be considered a D-allothreonine residue.

PMID- 16901116
TI  - Generation and reactivity of the phenyl cation in cryogenic argon matrices:
      monitoring the reactions with nitrogen and carbon monoxide directly by IR
      spectroscopy.
AB  - The phenyl cation 1 has been prepared by co-deposition of iodobenzene 6 or
      bromobenzene 7 with a microwave-induced argon plasma and characterized by IR
      spectroscopy in cryogenic argon matrices. The cation can clearly be identified by
      its strongest absorption at 3110 cm(-1) that is rapidly bleached upon visible
      light irradiation. This characteristic band is observed neither in the
      conventional photochemistry of 6 or 7 nor in discharge experiments with alkyl
      halides or chlorobenzene. The latter finding is in line with energetic
      considerations. According to density functional theory (DFT) computations, the
      strongest absorption of 1 is caused by a C-H stretching vibration that involves
      almost entirely the ortho-hydrogens. This is confirmed by isotopic labeling
      experiments. Co-deposition of halobenzene/N2 mixtures leads to a decrease of the
      3110 cm(-1) absorption, whereas several new signals are detected in the 2200-2400
      cm(-1) range of the IR spectrum. Annealing of a matrix that contains 1 and 1% N2
      leads to an increase of a broad band at 2260 cm(-1) that is assigned to the
      benzenediazonium ion 2. A sharp signal at 2327 cm(-1) that had previously been
      assigned to the N-N stretching vibration of 2 is due to molecular nitrogen. The
      mechanism that triggers the IR activity of N2 is not yet understood. Annealing of
      a matrix that contains 1 and 0.5% CO leads to an increase of a broad band at 2217
      cm(-1) that is considerably stronger than the 2260 cm(-1) absorption of 2. This
      signal is assigned to the C-O stretching vibration of the benzoyl cation 12, in
      excellent agreement with previous investigations of 12 in superacidic media. Some
      consequences of the measured frequencies with regard to bonding in 2 and 12 are
      discussed.

PMID- 16901117
TI  - Functionalization of N-[(silyl)methyl]-beta-lactam carbanions with carbon
      electrophiles.
AB  - Latent acidity of alpha-alkyl-alpha-amino-N-[(silyl)methyl]-beta-lactams enabled
      a concise entry to lithium nonenolate N-methyl-azetidinone carbanions lithiated
      alpha' to the beta-lactam nitrogen, owing to the stabilizing "alpha-effect" of
      one or two trimethylsilyl groups. (n)BuLi/TMEDA and (t)BuLi/TMEDA were the bases
      of choice for complete deprotonation of di- and monosilylated beta-lactams,
      respectively. Trapping of the resulting carbanions with alkyl halides provided
      the corresponding N-[(alpha'-silyl)-alkyl]-beta-lactams, while carbon dioxide and
      related electrophiles such as benzyl chloroformates or isocyanates, afforded the
      corresponding silicon-free N-carboxymethyl-, N-benzyloxycarbonylmethyl-, and N
      amidomethyl-beta-lactams in a single synthetic step. Likely structures of these
      unprecedented lithiated N-[(silyl)methyl]-beta-lactams were studied by MO
      calculations (B3LYP/6-31G**), and the origin of their relative stability was
      briefly discussed.

PMID- 16901118
TI  - Electrochemically induced cascade reaction for the assembly of libraries of
      biologically relevant 1,4-benzoxazine derivatives.
AB  - The scope and mechanism of an electrochemically induced cascade reaction, which
      leads to highly substituted 1,4-benzoxazine derivatives, have been explored
      through the variation of the structure of the o-azaquinone mediator. This
      reaction sequence, wherein both cycloaddition partners are generated in situ, at
      room temperature, under metal-free conditions, allows the regiospecific inverse
      electron-demand Diels-Alder (IEDDA) reaction of an o-azaquinone heterodiene and a
      secondary alkylenamine dienophile, two chemically nonaccessible unstable
      entities. The cascade reaction was found to be general with electron-poor o
      azaquinone entities generated from substituted 2-aminoresorcinol substrates. In
      the case of o-aminophenol derivatives which lack the 2-hydroxyl group, the
      generated o-azaquinone species failed to catalyze the oxidation of the amine to
      the corresponding imine, precursor of the enamine dienophile, because the absence
      of an intramolecular hydrogen bond at the origin of a highly reactive Schiff base
      cyclic transition state. To overcome this problem, a tandem oxidation-IEDDA
      reaction, in which the o-azaquinone is generated in the presence of a preformed
      enamine, has been developed as an alternative. These one-pot methodologies, which
      offer the opportunity to introduce variations in both cycloaddition partners,
      should be particularly useful for the development of libraries of biologically
      relevant 1,4-benzoxazine derivatives.

PMID- 16901119
TI  - An efficient computational approach for the evaluation of substituent constants.
AB  - Density functional theory computations at the B3LYP/6-311+G(2d,2p) and BPW91/6
      311G(d,p) levels were carried out for a series of 15 monosubstituted benzene
      derivatives to study dependencies between electronic structure parameters and
      experimental reactivity constants. An efficient and accurate computational
      approach for the evaluation of sigma(0) substituent constants for substituted
      benzene systems is outlined. It is based on the excellent linear correlation
      between the experimental reactivity constants and the theoretical electrostatic
      potential values (EPN) at the carbon atoms in the para and meta positions. The
      results underline the usefulness of the EPN as a local reactivity descriptor.
      Theoretical computations to assess the influence of water solvent using the
      SCIPCM method showed that the solvent enhances the overall effect of polar
      substituents by about 30%. The results obtained indicate also that the relative
      values of the sigma(0) constants are predominantly determined by intramolecular
      influences.

PMID- 16901120
TI  - Mechanism of the base-assisted displacement of chloride by alcohol in sulfinyl
      derivatives.
AB  - A computational study with density functional theory (DFT) is carried out on the
      reaction between methyl sulfinyl chloride (MSC) and methanol in the presence of
      trimethylamine, a process which is a general model for two different methods used
      in practice for the obtention of chiral sulfoxides through dynamic kinetic
      resolution. Two mechanistic options are considered: in one of them, chloride is
      initially displaced by the base (ion pair mechanism), whereas in the other,
      chloride stays bound to sulfur until its final displacement by methoxy (neutral
      mechanism). In both cases, the approach of the alcohol to sulfur is coupled with
      a hydrogen transfer from methanol to the oxo group of MSC in a single concerted
      transition state. The presence of a trimethylamine molecule facilitates
      substantially the reaction by reducing the nucleophilic substitution barrier by
      more than 10 kcal/mol through the formation of a N-H bond with the hydrogen atom
      being transferred. The neutral mechanism presents a free energy barrier lower
      than the ion pair alternative and is thus preferred.

PMID- 16901121
TI  - Strategies for expanding structural diversity available from olefin isomerization
      claisen rearrangement reactions.
AB  - Boron-substituted di(allyl) ethers provide an efficient conduit for expanding the
      structural diversity available from olefin isomerization-Claisen rearrangement
      (ICR) reactions. Easily prepared allyl propargyl ethers undergo chemoselective
      Zr(IV)-catalyzed hydroboration to afford the boron-substituted ICR substrates.
      The boron-substituted allyl residue undergoes chemoselective Ir(I)-catalyzed
      olefin isomerization and in situ Claisen rearrangement to afford stereodefined
      beta-boryl aldehyde products. Functionalization of the C-B linkage by oxidation
      or Suzuki cross-coupling provides a route to Claisen adducts previously
      inaccessible from the ICR methodology.

PMID- 16901122
TI  - Photolysis of heptanal.
AB  - Photolysis of heptanal is investigated from an experimental and theoretical point
      of view. Photoexcited heptanal is believed to undergo rapid intersystem crossing
      to the triplet manifold and from there undergoes internal H-abstraction to form
      biradical intermediates. The favored gamma-H abstraction pathway can cyclize or
      cleave to 1-pentene and hydroxyethene, which tautomerizes to acetaldehyde. Yields
      of 1-pentene and acetaldehyde were measured at 62 +/- 7% and 63 +/- 7%,
      respectively, relative to photolyzed heptanal. Additionally, small quantities of
      hexanal and hexanol were observed. On the basis of combined experimental and
      theoretical evidence, the remaining heptanal photolysis proceeds to form an
      estimated 10% HCO + hexyl radical and 30% cyclic alcohols, particularly 2-propyl
      cyclobutanol and 2-ethyl cyclopentanol.

PMID- 16901123
TI  - Templating photodimerization of coumarins within a water-soluble nano reaction
      vessel.
AB  - An octahedral Pd nanocage serves as a reaction vessel to control
      photodimerization of coumarins in water. The coumarin derivatives explored in
      this study react within the Pd nanocage to selectively yield a syn head-head
      dimer, whereas in water, they yield either a mixture of dimers or a different
      isomer. The selective dimerization is interpreted to mean that the monomers are
      preorganized by the cage through weak intermolecular forces. The selectivity
      obtained within the nanocage is more general and predictable compared to other
      hosts used previously to control the geometry of photodimerization reactions.

PMID- 16901124
TI  - Naphthalene-1,8-diylbis(diphenylmethylium) as an organic two-electron oxidant:
      benzidine synthesis via oxidative self-coupling of N,N-dialkylanilines.
AB  - Naphthalene-1,8-diylbis(diphenylmethylium) exhibits a unique electron-transfer
      reduction behavior due to the close proximity of the two triarylmethyl cations,
      which form a C-C bond while accepting two electrons, leading to 1,1,2,2
      tetraphenylacenaphthene. The preparation of the dication was readily accomplished
      under anhydrous conditions starting from a cyclic bis(triarylmethyl) ether,
      derived from 1,8-dibromonaphthalene. The process proceeded via deoxygenation
      accompanying the formation of a disiloxane on treatment with a silylating agent
      (Me3SiClO4 or Me3SiOTf) in 1,1,1,3,3,3-hexafluoropropan-2-ol. The dication was
      successfully employed for oxidative coupling of N,N-dialkylanilines at the para
      position to afford the corresponding benzidines in good to excellent yield.

PMID- 16901125
TI  - Synthesis of enantiopure (alphaS,betaS)- or (alphaR,betaS)-beta-amino alcohols by
      complete regioselective opening of aminoepoxides by organolithium reagents LiAlH4
      or LiAlD4.
AB  - The reaction of chiral (2R,1'S)- or (2S,1'S)-2-(1-aminoalkyl)epoxides, 1 or 2
      with a variety of organolithium compounds to obtain the corresponding
      (alphaS,betaS)- or (alphaR,betaS)- beta-amino alcohols in enantiopure form is
      reported. In both cases, the opening of the oxirane ring at C-3 proceeded with
      total regioselectivity. Moreover, the ring opening of aminoepoxides 1 or 2 by
      hydride (utilizing LiAlH4) to obtain the corresponding (2S,3S)- or (2R,3S)-3
      aminoalkan-2-ols is also described. The reaction of 1 or 2 with LiAlD4 in place
      of LiAlH4 gave the corresponding (2S,3S)- or (2R,3S)-3-amino-1-deuterioalkan-2
      ols.

PMID- 16901126
TI  - O-arylation versus C-arylation: copper-catalyzed intramolecular coupling of aryl
      bromides with 1,3-dicarbonyls.
AB  - The copper-catalyzed intramolecular coupling of aryl bromides with 1,3
      dicarbonyls via a six-membered ring closure was examined. With CuI (10 mol %) as
      the catalyst, N,N'-dimethylethylenediamine as the ligand, and Cs2CO3 as the base,
      the reactions of alpha-(2-bromobenzyl)-beta-keto esters in THF at refluxing
      temperature afforded the corresponding substituted 4H-1-benzopyrans in high
      yields via O-arylation. On the other hand, the reactions of delta-(2-bromophenyl)
      beta-keto esters in refluxing dioxane led to the formation of 3,4
      dihydronaphthalen-2(1H)-one derivatives via C-arylation.

PMID- 16901127
TI  - Baeyer-Villiger oxidation in supercritical CO2 with potassium peroxomonosulfate
      supported on acidic silica gel.
AB  - Supercritical carbon dioxide (scCO2) is an efficient reaction medium to perform
      the Baeyer-Villiger oxidation with hydrated silica-supported potassium
      peroxomonosulfate (h-SiO2.KHSO5) under flow-through conditions. Hydration
      modulates the reactivity of the active surface by softening the acidity of the
      KHSO4 present in the supported reagent. The reaction in scCO2 is much more
      efficient than in n-hexane under similar conditions, which is attributed to
      better transport and solvating properties of the supercritical medium with regard
      to n-hexane.

PMID- 16901128
TI  - Cationic Rh(I) catalyst in fluorinated alcohol: mild intramolecular cycloaddition
      reactions of ester-tethered unsaturated compounds.
AB  - In fluorinated alcohols, the cationic Rh(I) species, which is derived from
      [Rh(COD)Cl]2 and AgSbF6, efficiently catalyzed intramolecular [4+2] cycloaddition
      reactions of ester-tethered 1,3-diene-8-yne derivatives. The catalytic system was
      also effective in intramolecular [5+2] cycloaddition reactions of ester-tethered
      omega-alkynyl vinylcyclopropane compounds.

PMID- 16901129
TI  - An in-depth study on ring-closing metathesis of carbohydrate-derived alpha
      alkoxyacrylates: efficient syntheses of DAH, KDO, and 2-deoxy-beta-KDO.
AB  - Novel, efficient synthetic pathways to DAH, KDO, and 2-deoxy-beta-KDO are
      described. Ring-closing metathesis (RCM) of highly functionalized alpha
      alkoxyacrylate fragments resulted in a series of synthetically versatile oxygen
      heterocyclic intermediates. Further functionalization of the resulting enol ether
      double bond and subsequent deprotection provided the natural products in high
      overall yields, starting from commercially available protected sugars.

PMID- 16901130
TI  - Synthesis and crystallographic characterization of chiral bis-oxazoline-amides.
      Fine-tunable ligands for Pd-catalyzed asymmetric alkylations.
AB  - New chiral chelating C2 bis-oxazoline-amide ligands (1) exhibiting a highly
      flexible molecular structure have been prepared in high yield through a versatile
      synthetic pathway. Combined crystallographic, variable temperature (VT)-NMR, IR,
      and ESI-MS studies have been carried out to investigate the nature of the 1-Pd
      complexes that are effective tools in controlling the stereochemical outcome of
      Pd-catalyzed allylic alkylations (ee up to 98%).

PMID- 16901131
TI  - Ring currents in tangentially p-p bonded sigma-aromatic systems.
AB  - We report a theoretical study of ring systems that delocalize electrons in a
      cyclic array of p orbitals arranged tangentially in sigma-bonding fashion. Sigma
      bonded arrays are compared to conventional pi-bonded analogues with respect to
      orbital symmetry and aromatic/antiaromatic behavior. In a one-to-one
      correspondence between pi and tangential molecular orbitals of a cycle, local
      rotation turns each pi to a tangential basis function, changing bonding
      interactions to antibonding and inverting the order of filling of molecular
      orbitals. The ipsocentric ring-current mapping approach is used to evaluate
      aromaticity on the magnetic criterion. As for conventional pi-ring currents, the
      sigma-ring current in tangential p-p bonded systems is dominated by the HOMO-LUMO
      transition, corresponding to circulation of four electrons in diatropic (4n + 2)
      electron cycles but two in paratropic (4n)-electron cycles. The systems examined
      here utilize either C 2p or Si 3p orbitals for delocalization. Although
      interchangeable with C with respect to the fundamental orbital symmetry and ring
      current rules, Si bonds at greater internuclear distances, a feature that allows
      easier design of potentially stable sigma-aromatic structures. Calculations show
      the wheel-like Si10C50H70 structure 6 as a stable, neutral aromatic molecule with
      a diatropic ring current following the sigma-bond path formed by Si 3p orbitals.

PMID- 16901132
TI  - Molecular recognition thermodynamics of pyridine derivatives by
      sulfonatocalixarenes at different pH values.
AB  - The complex stability constants (Ka) and thermodynamic parameters (DeltaG
      degrees, DeltaH degrees, and TDeltaS degrees) for 1:1 complexation of water
      soluble calix[4]arene, thiacalix[4]arene, and calix[5]arene sulfonates with
      pyridine and their methylated derivatives have been determined by means of
      isothermal titration calorimetry at pH 2.0 and 7.2 at 298.15 K, and their binding
      modes have been investigated by NMR spectroscopy. The results obtained show that
      sulfonatocalixarenes afford stronger binding ability toward pyridine guests at pH
      2.0, attributable to the positive electrostatic interactions and the more
      extensive desolvation effects, but present higher molecular selectivity at pH 7.2
      owing to the strengthened C-H...pi interactions. The pH-responsible binding
      ability and molecular selectivity are discussed from the viewpoint of
      electrostatic, pi-stacking, van der Waals interactions and size-fit relationship
      between host and guest. A close comparison further demonstrates that the C-H...pi
      interactions and van der Waals interactions play a more important role than
      pi...pi interactions in the present inclusion complexation.

PMID- 16901133
TI  - 3,3'-Diphosphoryl-1,1'-bi-2-naphthol-Zn(II) complexes as conjugate acid-base
      catalysts for enantioselective dialkylzinc addition to aldehydes.
AB  - A highly enantioselective dialkylzinc (R(2)(2)Zn) addition to a series of
      aromatic, aliphatic, and heteroaromatic aldehydes (5) was developed based on
      conjugate Lewis acid-Lewis base catalysis. Bifunctional BINOL ligands bearing
      phosphine oxides [P(=O)R(2)] (7), phosphonates [P(=O)(OR)(2)] (8 and 9), or
      phosphoramides [P(=O)(NR(2))(2)] (10) at the 3,3'-positions were prepared by
      using a phospho-Fries rearrangement as a key step. The coordination of a NaphO
      Zn(II)-R(2) center as a Lewis acid to a carbonyl group in a substrate and the
      activation of R(2)(2)Zn(II) with a phosphoryl group (P=O) as a Lewis base in the
      3,3'-diphosphoryl-BINOL-Zn(II) catalyst could promote carbon-carbon bond
      formation with high enantioselectivities (up to >99% ee). Mechanistic studies
      were performed by X-ray analyses of a free ligand (7) and a tetranuclear Zn(II)
      cluster (21), a 31P NMR experiment on Zn(II) complexes, an absence of nonlinear
      effect between the ligand (7) and Et-adduct of benzaldehyde, and stoichiometric
      reactions with some chiral or achiral Zn(II) complexes to propose a transition
      state assembly including monomeric active intermediates.

PMID- 16901134
TI  - Diboron and triboron compounds based on linear and star-shaped conjugated ligands
      with 8-hydroxyquinolate functionality: impact of intermolecular interaction and
      boron coordination on luminescence.
AB  - New 8-R-quinoline functionalized linear and star-shaped conjugated molecules have
      been synthesized using Suzuki-Miyaura coupling methods (R = MeO, L1-L5; R =
      CH3OCH2O, L1'-L5'). When treated with HCl, L1'-L5' are converted readily to the
      corresponding 8-hydroxyquinoline compounds L(OH)1-L(OH)5 which react readily with
      BPh3 in refluxing THF to produce the corresponding polyboron chelate compounds B1
      B5 in good yields. L1-L5 and B1-B5 display similar thermal stability with Td at
      approximately 300 degrees C. Experimental and molecular orbital calculation
      results showed that the chelation by boron stabilizes the LUMO level of the
      ligand and narrows the HOMO-LUMO gap, resulting in the blue emission of the
      ligands and the green or orange emission of the boron compounds. Crystal
      structures of L1, L3, and L5 showed that these molecules have layered
      arrangements in the solid state with significant intermolecular pi-pi
      interactions. The linear diboron B5 displays concentration and temperature
      dependent emission in solution, attributable to intermolecular interactions. The
      properties of a monoboron compound BPh2(5-Ph-8-MeO-q) (B0) and its corresponding
      free ligand L0 were investigated and compared to the closely related diboron
      compound B1 and the ligand L1, which revealed that the increase of the number of
      chromophores linked by an aromatic group has a significant impact on thermal
      stability and the HOMO and LUMO energy levels.

PMID- 16901135
TI  - Solid phase approaches to N-heterocycles using a sulfur linker cleaved by SmI2.
AB  - A sulfur HASC (alpha-hetero-atom substituted carbonyl) linker has been utilized
      in solid-phase approaches to oxindoles and tetrahydroquinolones. The route to
      oxindoles employs the first Pummerer cyclizations on solid phase, whereas the
      route to tetrahydroquinolones involves a microwave-assisted Heck reaction
      followed by a Michael cyclization. In both cases, the linker is cleaved in a
      traceless fashion by electron transfer from samarium(II) iodide. The routes
      illustrate the compatibility of the linker system with a number of reaction types
      and its utility for library synthesis.

PMID- 16901136
TI  - A general and efficient palladium-catalyzed intramolecular cyclization reaction
      of beta-brominated porphyrins.
AB  - A general and efficient synthesis of fused five-membered porphyrins from the
      readily available beta-brominated porphyrins via palladium-catalyzed
      intramolecular cyclization has been developed, which can be applied for various
      metal complexes of beta-brominated porphyrins or free base ones and generally
      results in good yields of the fused five-membered porphyrins.

PMID- 16901137
TI  - Conformations of cycloundecane.
AB  - Cycloundecane (1) was shown to exist at -183.1 degrees C as a mixture of the
      [12323] (approximately 59%) and [335] (approximately 41%) conformations.
      Populations were determined from the (13)C NMR spectrum, and assignments were
      based on the (13)C spectra, calculated free energies and chemical shifts, and
      information from the literature, including X-ray studies of solid derivatives and
      calculated barriers.

PMID- 16901138
TI  - A new general route to thiophenophanes: synthesis and properties of
      [n](2,5)thiophenophane-1,n-diones.
AB  - A series of [n](2,5)thiophenophane-1,n-diones (5) (n = 9, 10, 12, 14, 16, and 20)
      were synthesized in a simple four-step route starting from the appropriate
      1,omega-oligomethylenedicarboxylic acids. The bis(halomethylketones) (6), which
      were obtained by successive treatment of the diacids with SOCl2, diazomethane,
      and HBr or HCl, were cyclized by Na2S under high dilution conditions. The
      obtained monomeric cyclic diketosulfides (4) were condensed with glyoxal in MeOH
      by slowly adding dilute NaOMe affording 5. The thiophene-2,5-dicarbonyl moiety of
      5 (n = 9) is significantly deformed as shown by X-ray crystallography, and the
      effect of the strain is reflected in the C=O stretching frequencies and the pi
      pi* and the n-pi* absorptions.

PMID- 16901139
TI  - Synthesis of bulky and electron-rich MOP-type ligands and their applications in
      palladium-catalyzed C-N bond formation.
AB  - A series of 2-dialkylphosphino-2'-alkoxy-1,1'-binaphthyl ligands (6a-c and 8a-c)
      have been prepared conveniently by a lithium-initiated ring-opening reaction of
      dinaphthofuran, followed by selective phosphorylation. These compounds displayed
      a remarkable air and moisture stability, both in solid form and in solution.
      Application of these phosphine ligands in palladium-catalyzed C-N bond forming
      reactions revealed the crucial roles of the steric bulk of the substituents on
      the phosphorus atom governing the catalytic activity. Specifically, 2-di-tert
      butylphosphino-2'-isopropoxy-1,1'-binaphthyl (8b) proved to be the most effective
      for the aminations of aryl halides with primary amines, while the less bulky 2
      dicyclohexyl-2'-methoxy-1,1'-binaphthyl (6a) was more effective for the
      aminations with secondary amines. The steric and electronic effects of the
      ligands were analyzed to account for these observations.

PMID- 16901140
TI  - Stille coupling reactions in the synthesis of hypoxia-selective 3-alkyl-1,2,4
      benzotriazine 1,4-dioxide anticancer agents.
AB  - The introduction of a 3-alkyl substituent is a key step in the synthesis of 1,2,4
      benzotriazine 1,4-dioxide hypoxia-selective anticancer agents, such as SN29751.
      The Stille reaction of 3-chloro-1,2,4-benzotriazine 1-oxides (BTOs) 5 was
      inhibited by the presence of electron donating substituents on the benzo ring,
      thus limiting the range of compounds available for SAR studies. The use of 3-iodo
      BTOs 8 did not provide a significant improvement in the yields of 3-ethyl-BTOs 6.
      Microwave-assisted Stille coupling of chlorides 5 gave dramatically improved
      yields, which were consistently superior to those from the corresponding iodides
      8. The application of microwave-assisted synthesis extended the range of
      substituted BTOs available for SAR studies and provided an efficient, scalable
      synthesis of the investigational anticancer agent, SN29751 (1).

PMID- 16901141
TI  - First asymmetric cycloaddition of carbonyl ylides to vinyl sulfoxides and furan
      2(5H)-ones.
AB  - The Rh2(OAc)4-catalyzed reactions of o-(methoxycarbonyl)-alpha-diazoacetophenone
      with enantiomerically pure 5-ethoxy-3-p-tolylsulfinylfuran-2(5H)-ones 1a and 1b
      afford 4,10-epoxybenzo[4,5]cyclohepta[1,2-c]furan-3,9-diones 6a and 6b, in good
      or moderate yields and in a completely regioselective way. The pi-facial
      selectivity is complete for 1a, which only yields anti-6a adducts, and very high
      for 1b. The endo stereoisomers are favored with respect to the exo ones in both
      reactions. The sulfinyl group significantly increases the reactivity of the
      dipolarophile as it has been demonstrated by studying the behavior of 5
      methoxyfuran-2(5H)-one (3).

PMID- 16901142
TI  - Stereoselective [4 + 1] annulation reactions with silyl vinylketenes derived from
      Fischer carbene complexes.
AB  - Stable silyl vinylketenes were prepared via the thermal reaction of Fischer
      carbene complexes with triisopropylsilyl- or tert-butyldimethylsilyl-substituted
      alkynes. The ability of these silyl vinylketenes to participate with carbenoid
      reagents in [4 + 1] annulation reactions was investigated. The best results were
      obtained with diazomethane and substituted diazomethane reagents, which provided
      cyclopentenone products in excellent yields and essentially complete
      stereoselectivity.

PMID- 16901143
TI  - General strategy for the syntheses of corynanthe, tacaman, and oxindole
      alkaloids.
AB  - We report herein the total synthesis of the corynanthe alkaloid
      dihydrocorynantheol and the formal syntheses of the indole alkaloids tacamonine,
      rhynchophylline, and hirsutine. The strategies for assembling the corynanthe and
      tacaman skeletal frameworks comprised of both the classical ABD --> ABCD and ABC 
      -> ABCD approaches wherein the variously substituted piperidinone D-rings were
      formed via ring-closing metathesis (RCM) followed by a 1,4-addition to introduce
      the requisite side chain at C(15). Since 1,4-additions to alpha,beta-unsaturated
      lactams represent an underdeveloped field, we conducted a series of studies with
      two unsaturated lactams employing organocuprates and metal enolates as the
      nucleophiles. These studies revealed that organocuprates derived from Grignard
      reagents and either stoichiometric amounts of CuCN or catalytic amounts of
      CuBr.DMS complex are excellent nucleophiles for such additions; TMSCl was a
      crucial additive for optimizing these reactions. The anion derived from ethyl 1,3
      dithiolane-2-carboxylate was also an excellent nucleophile in these 1,4
      additions, although the stereochemistry of such 1,4-additions to carboline
      derived, unsaturated lactams was sensitive to substitution on the indole nitrogen
      atom. The ABD --> ABCD approach to these alkaloids featured a novel one-pot
      sequence of an RCM reaction and a zirconocene-catalyzed carbomagnesation followed
      by a second RCM to generate the D-ring.

PMID- 16901145
TI  - Synthesis and selected reactions of a bicyclic sultam having sulfur at the apex
      position.
AB  - A practical synthesis of the bicyclic dienyl sultam 9 has been developed. The
      viable route involved several key steps. Of these, ring-closing metathesis
      represented by the conversion of 19 to 20 had to be implemented in advance of the
      assembly of other rings such as is present in 15. Product 20 was used as the
      template for more advanced framework construction, as in 16. The second double
      bond was best introduced by a bromination-dehydrobromination sequence, the 2-fold
      loss of HBr being achieved most reliably by the use of tetra-n-butylammonium
      fluoride in CH2Cl2 or DMSO. The direct irradiation of 9 gave rise to the endo
      oriented cyclobutene derivative 30. The title diene is not a ready participant in
      Diels-Alder reactions. When heated with endo-bornyltriazolinedione in ethyl
      acetate solution, conversion to a 1:1 mixture of 33 and its diastereomer occurred
      as confirmed by X-ray crystallographic analysis. From the mechanistic
      perspective, this transformation constitutes an interesting example of a
      stereocontrolled and regioselective [2+2] cycloaddition followed by a
      vinylcyclobutane-cyclohexene rearrangement. Products 30 and 33 constitute
      examples of strained sulfonamides featuring a norbornyl-like structural
      component.

PMID- 16901144
TI  - Facile entry to substituted decahydroquinoline alkaloids. Total synthesis of
      lepadins A-E and H.
AB  - Condensation of a L-alanine derived delta-bromo-beta-silyloxy-propylamine with
      1,3-cyclohexadione followed by alkylative cyclization produces a bicyclic enone.
      Diastereoselective Pt/C-catalyzed hydrogenation of this enone in HOAc provides a
      5-oxo-cis-fused decahydroquinoline. Wittig olefination of this decahydroquinoline
      and subsequent epimerization of the resulting 5-formyl intermediate gives rise to
      a 5-beta-formyl decahydroquinoline exclusively. In a parallel procedure, Peterson
      reaction of this decahydroquinoline and subsequent hydrogenation of the generated
      5-exo-olefin provides a decahydroquinoline with a 5-alpha-substituent
      predominantly. For these two diastereoselective processes, using the
      intermediates without N-protection as the substrates is essential because the
      corresponding N-Boc intermediates give poor diastereoselectivity. The
      intermediate with beta-form side chain is further converted into lepadins A-C via
      carbon chain elongation, while the intermediate with alpha-form side chain is
      transformed into lepadins D, E, and H and corresponding 5'-epimers via connection
      with two sulfones generated from two Sharpless epoxidation products. By
      comparison of the rotations and NMR data, the stereochemistry of lepadins D, E,
      and H is assigned as 2S,3R,4aS,5S,8aR,5'R.

PMID- 16901146
TI  - Bottom-up synthesis of optically active oligonaphthalenes: three different
      pathways for controlling axial chirality.
AB  - The oxidative homocoupling of optically active binaphthalenes 1a-d with a
      stoichiometric amount of CuCl2 and amines afforded quaternaphthalenes 2a-d in up
      to 93% de. The high diastereoselectivities were achieved through three different
      pathways (epimerization of the axis together with diastereoselective
      crystallization, thermodynamic, and kinetic control pathways). The type of side
      chains on the naphthalene influenced which pathway dominates. Three pathways were
      applicable to octinaphthalenes (8a-d) and hexadecanaphthalene 10a with 46-99% de.
      The absolute configuration of the newly formed axial bond was determined by (1) X
      ray crystallographic analysis, (2) transformation to known compounds 15 and 16,
      (3) CD spectra of oligonaphthalenes with two pyrene rings as exciton parts, and
      (4) the shift values in 13C NMR spectra of 13C-enriched derivatives 29-31 toward
      chiral shift reagent Eu(+tfc)3.

PMID- 16901147
TI  - Stereoselective three-component synthesis of trans-endo-decahydroquinolin-4-one
      derivatives from aldehydes, aniline, and acetylcyclohexene.
AB  - The diastereoselective synthesis of trans-endo-decahydroquinolin-4-one (4) via a
      three-component reaction of aldehydes (1), anilines (2), and 1-acetylcyclohexene
      (3) in the presence of iodine in a one-pot reaction at room temperature is
      described. The short reaction time, easy workup, excellent yield, and mild
      reaction conditions make this novel annulation strategy both practical and
      attractive.

PMID- 16901148
TI  - Skraup-Doebner-Von Miller quinoline synthesis revisited: reversal of the
      regiochemistry for gamma-aryl-beta,gamma-unsaturated alpha-ketoesters.
AB  - A reversal of the standard regiochemistry of the Skraup-Doebner-Von Miller
      quinoline synthesis was observed when anilines were condensed with gamma-aryl
      beta,gamma-unsaturated alpha-ketoesters in refluxing TFA. The reaction is
      proposed to involve 1,2-addition of the anilines to gamma-aryl-beta,gamma
      unsaturated alpha-ketoesters to form Schiff's base adducts, followed by
      cyclization and oxidation. The products were unambiguously shown to the 2-carboxy
      4-arylquinolines by spectroscopy and X-ray crystallographic analysis.

PMID- 16901149
TI  - Inter- and intramolecular-bridge-mediated electron transfer in aliphatic halides.
AB  - The anionic surfaces of the 1-chloro- and 4-chlorobicyclo[2.2.1]heptan-2-one, 1
      chloro- and 4-chlorobicyclo[2.2.2]octan-2-one, 1-chloro- and 5-chloroadamantan-2
      one, and 2-chlorotricyclo[7.3.1.0(2,7)]tridecan-13-one were explored using DFT
      functionals with full geometry optimization in solution. The reductive cleavage
      of these compounds is controlled by the rigidity of the polycycle, its capability
      to form an unstrained radical, and by the relative carbonyl/C-Cl disposition on
      the bridge. Such control can be exerted by either a concerted-dissociative or a
      stepwise mechanism with radical anions as intermediates. 5-Chloroadamantan-2-one
      is the most suitable compound to follow the latter pathway.

PMID- 16901150
TI  - Guanidinium ylide mediated aziridination: identification of a spiro imidazolidine
      oxazolidine intermediate.
AB  - We successfully isolated a spiro imidazolidine-oxazolidine intermediate in the
      reaction of guanidinium ylide mediated aziridination using alpha
      bromocinnamaldehyde. X-ray crystallographic analysis unambiguously revealed that
      the stereogenic centers of the spiro intermediate were in a trans configuration.
      The role of the spiro compound as an intermediate in the aziridination reaction
      was confirmed by observation of its smooth chemical conversion into aziridine
      products.

PMID- 16901151
TI  - A novel method for the separation of bis(alpha-hydroxyalkyl)phosphinic acid
      diastereoisomers via formation of novel cyclic phosphinic acids.
AB  - The reaction of aromatic and aliphatic aldehydes with hypophosphorus acid under
      microwave irradiation was examined. The reaction gave a mixture of a racemic pair
      of bis(alpha-hydroxyalkyl)phosphinic acids and acetal derivatives from the
      corresponding bis(alpha-hydroxyalkyl)phosphinic acids of meso-stereochemistry in
      good yield. The difference in solubility in organic solvents due to polarity
      allowed us to readily separate these compounds. This method constitutes an easy,
      rapid, and good-yielding preparation and separation of bis(alpha-hydroxyalkyl)
      phosphinic acid diastereoisomers from simple starting materials using microwave
      irradiation.

PMID- 16901152
TI  - A matrix isolation study of 2-isopropylidenecyclopentane-1,3-diyl (Berson-type
      diradical).
AB  - The photodenitrogenation of diazene 5 in an argon matrix at 10 K permitted the
      first observation of an IR spectrum of 2-isopropylidenecyclopentane-1,3-diyl 2 (a
      Berson-type diradical). A comparison of the IR spectrum with a vibrational
      simulation at the B3LYP/6-31G(d) level of theory revealed that the diradical 2
      has a planar structure. The oxygen-trapping reaction of 2 produced
      regioselectively fused peroxide 6 in an oxygen-doped argon matrix at 10 K.
      Irradiation of the diradical 2 afforded enyne 8 in an argon matrix at 10 K.

PMID- 16901153
TI  - Fluoride-sensing calix-luminophores based on regioselective binding.
AB  - Bifunctional (fluorescence and visible light absorption) anion-sensing compounds
      1 and 2 based on calix[4]arene platform with 4-nitrophenylazo and pyrene moieties
      have been developed. The two NHs of the amide groups of 1 bind the fluoride anion
      through the H-bonding. This changes the characteristic excimer emission and forms
      a new emission peak from a static excimer. In 2, two OHs bind the fluoride anion,
      and this changes the characteristic absorption spectrum. The DFT calculation
      supports the regioselective binding of the fluoride anion, which is responsible
      for the different sensing property.

PMID- 16901154
TI  - X-ray and density functional theory structural study of 1,3,5,7,9-penta-tert
      butylcorannulene, C40H50.
AB  - The first X-ray structural characterization of an alkyl-substituted corannulene,
      namely, 1,3,5,7,9-penta-tert-butylcorannulene (C40H50), has been accomplished.
      The addition of bulky tert-butyl groups to the corannulene core flattens the bowl
      and affects the solid-state packing. The presence of two enantiomers, in addition
      to positional disorder of the C40H50 bowls in the solid-state structure, has
      prevented the acquisition of accurate geometric parameters of this open geodesic
      polyarene. Therefore, DFT calculations have been used to describe its molecular
      geometry and to access bond lengths, bond angles, and a bowl depth.

PMID- 16901155
TI  - Synthesis of 2H-indazoles via Lewis acid promoted cyclization of 2
      (phenylazo)benzonitriles.
AB  - Lewis-acid promoted "coarctate" cyclization of 10 2-(phenylazo)benzonitrile
      derivatives furnishes the isoindazole ring system in ca. 65-95% yield. A
      plausible mechanism for this unusual transformation is proposed.

PMID- 16901156
TI  - Incorporating a flexible crown ether into neutral discrete self-assemblies driven
      by metal coordination.
AB  - Driven by metal coordination, a flexible crown ether was self-assembled into
      neutral discrete complexes with two organoplatinum acceptors. Specifically, a [1
      + 1]-assembled structure was separated from self-assemblies with different
      stoichiometries by vapor diffusion of acetone into their dichloromethane
      solution. The formation of these crown ether-incorporated self-assemblies was
      confirmed by NMR, elemental analysis, and X-ray single-crystal analysis.

PMID- 16901157
TI  - Synthesis and structure of 2,6,14- and 2,7,14-trisubstituted triptycene
      derivatives.
AB  - A series of 2,6,14- and 2,7,14-trisubstituted triptycene derivatives were
      efficiently synthesized and their structures were determined by NMR, MS spectra,
      and X-ray analysis. These trisubstituted triptycenes are potential building
      blocks for constructing novel receptors and synthetic molecular machines.

PMID- 16901158
TI  - Stereoselective Michael addition of carbon-, nitrogen-, oxygen-, and sulfur
      centered nucleophiles on enantiopure hydroxylated 6,7-dehydro-5-oxoindolizidine.
      Synthesis of carbon- or hetero-7-substituted swainsonine analogues.
AB  - Enantiopure alpha,beta-unsaturated delta-lactams 1 and 2 react stereoselectively
      with carbon-, nitrogen-, sulfur-, and oxygen-centered nucleophiles. The synthetic
      potential of these conjugate additions is demonstrated through the synthesis of
      two new substituted indolizidines: (7R)-7-amino-8-deoxyswainsonine 3 and (7R)-7
      acetylaminoswainsonine 4.

PMID- 16901159
TI  - Palladium(0)-catalyzed highly regio- and stereoselective addition of
      organoboronic acids with 1,2-allenylphosphonates forming tri- or tetrasubstituted
      1(E)-alkenylphosphonates.
AB  - A highly regio- and stereoselective palladium(0)-catalyzed addition of
      organoboronic acids with 1,2-allenylphosphonates in the presence of HOAc forming
      tri- or tetrasubstituted 1(E)-alkenylphosphonates is reported in this paper. The
      stereoselectivity is much higher than the reported cases. The effects of
      different R(1), R(2), and R(3) were studied. A mechanism of this reaction is
      proposed on the basis of our previous study.

PMID- 16901160
TI  - Iron-catalyzed homocoupling of bromide compounds.
AB  - The homocoupling of bromide compounds was successfully performed in one pot by a
      combination of metallic magnesium and a catalytic amount of iron salts. The
      binary catalytic system differentiates itself from other homocoupling reactions
      catalyzed by iron salts in that it requires neither the in situ preparation of
      Grignard reagent nor the addition of a 1,2-dihalogen compound as an oxidant.
      Various aromatic and alkyl bromides underwent the homocoupling smoothly affording
      the corresponding symmetrical hydrocarbon compounds in moderate to excellent
      yields.

PMID- 16901161
TI  - Dakin-West synthesis of beta-aryl ketones.
AB  - Triethylamine and 1-methylimidazole were found to be selective catalysts for the
      Dakin-West synthesis of diaryl ketones and aryl methyl ketones, respectively. In
      the 1-methylimidazole-catalyzed reaction, catalysis is due to the simultaneous
      formation of both an effective acylating agent, 1-acyl-3-methylimidazolium, and a
      base, carboxylate anion. Hydrocinnamic acid, a compound previously reported to be
      unreactive under Dakin-West conditions, forms 4-phenyl-2-butanone when the
      reaction is catalyzed by 1-methylimidazole.

PMID- 16901162
TI  - Incorporation of 2,6-di(4,4'-dipyridyl)-9-thiabicyclo[3.3.1]nonane into discrete
      2D supramolecules via coordination-driven self-assembly.
AB  - The synthesis and characterization of three new supramolecular complexes 6-8 (a
      rhomboid and two hexagons) via coordination-driven self-assembly are reported in
      excellent yields (>90%). These assemblies have 2,6-di(4,4'-dipyridyl)-9
      thiabicyclo[3.3.1]nonane 2 as the bridging tecton. All assemblies were
      characterized by multinuclear NMR (1H and 31P), mass spectrometry (ESI-MS and ESI
      FT-ICR), and elemental analysis. The X-ray structure of the 120 degrees tecton 2
      is also discussed.

PMID- 16901163
TI  - A new method for the synthesis of 2-hydroxy-3-nitro-1,4-naphthoquinones:
      application to regiospecific preparation of unsymmetrical nitrobiquinones.
AB  - Novel 2-hydroxy-3-nitro-1,4-naphthoquinones were synthesized by an improved
      method utilizing nitronium tetrafluoroborate in high yields. A subsequent
      conversion to 2-chloro-3-nitro-1,4-naphthoquinones and a substitution of the
      chlorine by hydroxyquinone anions yielded 3-nitro-2,2'-binaphthoquinones with a
      complete regiocontrol.

PMID- 16901164
TI  - ZnO as a new catalyst for N-formylation of amines under solvent-free conditions.
AB  - The treatment of amines with formic acid in the presence of ZnO under solvent
      free conditions brings about highly and efficient N-formylation to give the
      corresponding formamides in excellent yields. The N-formylation reaction not only
      involves mild conditions, simple operation, and high yields but also high
      chemoselectivity.

PMID- 16901165
TI  - Cobalt-catalyzed aziridination with diphenylphosphoryl azide (DPPA): direct
      synthesis of N-phosphorus-substituted aziridines from alkenes.
AB  - A new catalytic aziridination system that consists of cobalt(II)
      tetraphenylporphyrin [Co(TPP)] as the catalyst and diphenylphosphoryl azide
      (DPPA) as the nitrene source has been developed. The cobalt-based catalytic
      system allows direct synthesis of N-phosphorus-substituted aziridines from
      alkenes with dinitrogen as the byproduct. Cobalt ion seems essential to the
      catalytic aziridination with DPPA as no or only trace amounts of the desired
      products were observed with other metal complexes of tetraphenylporphyrin.

PMID- 16901166
TI  - Synthesis of new cyclic dialkoxy disulfides.
AB  - Five new cyclic dialkoxy disulfides have been synthesized and fully
      characterized. An X-ray structure was obtained for the 2,3-furandimethylene
      dialkoxy disulfide.

PMID- 16901167
TI  - Ambidentate ligands capable of variable bond angles in the coordination-driven
      self-assembly of discrete Pt macrocycles.
AB  - Flexible, ambidentate pyridyl-carboxylate based donor ligands such as sodium 3-(3
      pyridyl)benzoate, sodium 4-(3-pyridyl)benzoate, and potassium 4-(3
      pyridyl)ethynylbenzoate self-assemble into discrete [2 + 2] macrocyclic species
      instead of infinite networks when combined with a 90 degrees platinum-containing
      acceptor. In each case, only one isomeric ensemble is selectively formed in high
      yield. All products are characterized by electrospray ionization mass
      spectrometry (ESI-MS) and 31P{1H} and 1H NMR spectroscopy. They are the first
      examples of discrete supramolecules incorporating flexible, ambidentate donor
      ligands. Despite their potential versatility, these pyridyl-carboxylate donors
      adjust their bonding directionality to accommodate a rigid platinum acceptor in
      the formation of one discrete ensemble.

PMID- 16901168
TI  - Isopinocampheylborane derivatives with >99% ee via the DMAP complex.
AB  - The complex 8 of isopinocampheylborane and p-(dimethylamino)pyridine (DMAP) can
      be obtained with >99% ee starting from alpha-pinene with 80-90% ee by
      hydroboration using DMAP.BH3 (5) activated by 5% iodine, or by the conventional
      hydroboration of alpha-pinene, followed by addition of DMAP. Purification of the
      air-stable 8 is readily accomplished by crystallization from methanol. Conversion
      of 8 into the trifluoroborate adduct 1 using KHF2 occurs without erosion of ee.
      Generation of the derived 2 in situ with TMSCl as the fluorophile also occurs
      with little, if any, loss of ee, as evidenced by the preparation of the
      salicaldimine complex 11 and the derived amino alcohol 12 with 94% ee overall.

PMID- 16901169
TI  - Synthesis and stereochemistry of the antitumor diterpenoid (+)-zerumin B.
AB  - Starting from commercially available (+)-sclareolide, the first synthesis of
      zerumin B was achieved by a concise, highly efficient pathway featuring
      stereoselective addition of a new silyloxyfuryltitanium reagent to an aldehyde
      intermediate and silyloxyfuran oxyfunctionalization as key steps. The synthesis
      established the relative and absolute configuration of zerumin B along with its
      identity with a purportedly new diterpenoid isolated from the plant Renealmia
      alpinia.

PMID- 16901170
TI  - Mandelamide-zinc-catalyzed enantioselective alkyne addition to heteroaromatic
      aldehydes.
AB  - The (S,S)-mandelamide III catalyzes the additions of both aryl- and
      alkylalkynylzinc reagents to heteroaromatic aldehydes with good yields and
      enantioselectivities up to 92%. This catalyst is easily prepared in a one-step
      procedure, and both enantiomers are available. Unlike most other described
      methods, using this catalyst does not require the addition of Ti(O(i)Pr)4.

PMID- 16901171
TI  - Regiocontrolled synthesis of pyrrole-2-carboxaldehydes and 3-pyrrolin-2-ones from
      pyrrole Weinreb amides.
AB  - A regiocontrolled synthesis of 3,4-disubstituted pyrrole-2-carboxaldehydes was
      completed in two steps from acyclic starting materials. A Barton-Zard pyrrole
      synthesis between N-methoxy-N-methyl-2-isocyanoacetamide and alpha-nitroalkenes
      or beta-nitroacetates provided N-methoxy-N-methyl pyrrole-2-carboxamides (pyrrole
      Weinreb amides), which were converted into the corresponding pyrrole-2
      carboxaldehydes by treatment with lithium aluminum hydride. A regioselective
      oxidation of the pyrrole-2-carboxaldehydes gave the corresponding 3,4
      disubstituted 3-pyrrolin-2-ones.

PMID- 16901172
TI  - Total synthesis of antofine using the net [5+5]-cycloaddition of gamma,delta
      unsaturated carbene complexes and 2-alkynylphenyl ketones as a key step.
AB  - A compound containing all of the carbons of the anticancer agent antofine was
      produced in a single step from the coupling of a gamma,delta-unsaturated carbene
      complex with a 2-alkynylphenyl ketone derivative. Subsequent conversion to
      antofine was effected in three steps.

PMID- 16901173
TI  - De novo asymmetric syntheses of muricatacin and its analogues via dihydroxylation
      of dienoates.
AB  - A short and highly efficient route to both enantiomers of muricatacin as well as
      the C-5-epimer has been developed. The key to the overall transformation is the
      highly regio- and enantioselective Sharpless asymmetric dihydroxylation of an
      (E,Z)-dienoate. The highly efficient stereoselective synthesis prepares (-)
      muricatacin in seven steps and 66% overall yield.

PMID- 16901174
TI  - Total synthesis of (+)-hygrine via asymmetric phase-transfer catalytic
      alkylation.
AB  - The first enantioselective synthesis of (+)-hygrine (1) is reported. 1 was
      obtained in 12 steps with 29% overall yield and 97% ee via asymmetric phase
      transfer catalytic alkylation and ring-closing metathesis as key steps. The
      absolute configuration of (+)-hygrine could be directly confirmed as R.

PMID- 16901175
TI  - Solid-phase synthesis of dinucleoside and nucleoside-carbohydrate phosphodiesters
      and thiophosphodiesters.
AB  - Unprotected nucleosides (ROH) were reacted with two polymers bound to N,N
      diisopropylamino-1,3,2-oxathiaphospholane in the presence of 1H-terazole.
      Oxidation with tert-butyl hydroperoxide or sulfurization with Beaucage's reagent,
      followed by the 1,3,2-oxathiaphospholane ring opening with unprotected
      nucleosides or carbohydrates (R'OH) in the presence of DBU, afforded nucleoside
      (5'-5')-nucleoside or nucleoside-carbohydrate phosphodiester and
      thiophosphodiester derivatives through the elimination of polymer-bound ethylene
      episulfide. This strategy offers the advantages of facile isolation of final
      products and monosubstitution of unprotected nucleosides and carbohydrates.

PMID- 16901176
TI  - Revisiting nucleophilic substitution reactions: microwave-assisted synthesis of
      azides, thiocyanates, and sulfones in an aqueous medium.
AB  - A practical, rapid, and efficient microwave (MW) promoted synthesis of various
      azides, thiocyanates, and sulfones is described in an aqueous medium. This
      general and expeditious MW-enhanced nucleophilic substitution approach uses
      easily accessible starting materials such as halides or tosylates in reaction
      with alkali azides, thiocyanates, or sulfinates in the absence of any phase
      transfer catalyst, and a variety of reactive functional groups are tolerated.

PMID- 16901177
TI  - Tandem Diels-Alder cycloadditions of 2-pyrone-5-acrylates for the efficient
      synthesis of novel tetracyclolactones.
AB  - Readily prepared from the regioselective Pd-catalyzed coupling reactions of 3,5
      dibromo-2-pyrone, 3-bromo-2-pyrone-5-carboxylates undergo tandem uninterrupted
      sequential Diels-Alder cycloaddition reactions with allyl vinyl ethers in a
      highly regio- and stereoselective fashion to provide a series of novel
      tetracyclolactones in good yields.

PMID- 16901178
TI  - Ag(I)-catalyzed sequential C-C and C-O bond formations between phenols and dienes
      with atom economy.
AB  - Mild, efficient, and economical Ag(I)-catalyzed sequential C-C/C-O bond
      formations between phenols and dienes were developed to afford in good yields a
      variety of dihydrobenzopyran and dihydrobenzofuran ring systems, which are
      important motifs in both naturally occurring and biologically active compounds.

PMID- 16901179
TI  - Facile cleavage of disulfides and preparation of unsymmetrical sulfides,
      thioglycosides and Michael adducts using triphenylphosphine.

PMID- 16901180
TI  - Single-day therapy for recurrent genital herpes.
AB  - Genital herpes, an incurable viral disease that can have a devastating impact on
      affected patients, is a serious public health concern affecting one in four
      Americans. Episodic treatment with nucleoside analogs for 3-5 days is the most
      common method of treatment; however, since maximum viral replication occurs
      within 24 hours after the onset of symptoms, single-day patient-initiated
      episodic treatment may be a better option. A recent study evaluated the
      effectiveness of patient-initiated single-day famciclovir versus placebo in the
      treatment of genital herpes and found that single-day famciclovir decreased
      healing time and the duration of pain and other symptoms, and increased the
      proportion of patients who did not progress to a full outbreak. Compared with
      previous studies, the results of single-day therapy are similar to or better than
      the results of conventional therapies of 2-5 days' duration. In addition, the
      convenience of single-day treatment may lead to greater patient adherence and
      improved overall management of recurrent herpes outbreaks.

PMID- 16901181
TI  - Efficacy and economics of topical calcineurin inhibitors for the treatment of
      atopic dermatitis.
AB  - Atopic dermatitis is a chronic, relapsing inflammatory skin disease that
      frequently affects infants and children. The worldwide prevalence of atopic
      dermatitis is estimated to be 5-20% of the pediatric population. Studies have
      shown that atopic dermatitis is associated with considerable economic costs and
      decreased quality of life. There is no proven curative therapy at present for
      atopic dermatitis; first-line therapy has generally consisted of dry skin care,
      avoidance of triggers, application of topical corticosteroids, and administration
      of histamine H1 receptor antagonists (antihistamines) and oral antibacterials as
      appropriate. Topical corticosteroids, while effective in many patients, carry the
      concern of local and systemic adverse effects. As a result, physicians and
      patients are reluctant to utilize stronger topical corticosteroids in certain
      areas of the body and for prolonged periods of time. The purpose of this article
      is to review the efficacy and economics of topical calcineurin inhibitors in the
      treatment of atopic dermatitis. This new class of agents (specifically tacrolimus
      ointment and pimecrolimus cream) represents an exciting advance in the treatment
      of atopic dermatitis. Clinical data show that topical calcineurin inhibitors are
      effective and do not cause the adverse effects associated with topical
      corticosteroids. Several studies have provided evidence that topical calcineurin
      inhibitors positively affect the quality of life of patients and their
      caregivers. Compared with branded topical corticosteroids and previous standards
      of care, topical calcineurin inhibitors appear to be a cost-effective treatment
      option. Drawing comparisons between tacrolimus and pimecrolimus is difficult
      because definitive head-to-head comparative studies involving these drugs have
      not been conducted.

PMID- 16901182
TI  - A comprehensive review of the long-term and short-term treatment of melasma with
      a triple combination cream.
AB  - Melasma is a common disorder of hyperpigmentation and generally involves areas of
      the face and neck. Hyperpigmentation is especially prevalent in darker complected
      patients and is often difficult to treat. Hydroquinone, tretinoin, and topical
      corticosteroids are well established monotherapeutic agents for treating melasma
      and hyperpigmentation; however, a stable, once-daily formulation triple
      combination cream containing 0.05% tretinoin, 4.0% hydroquinone, and 0.01%
      fluocinolone acetonide (Tri-Luma) represents the only commercially available
      combination of all three agents. This product is approved by the US FDA for the
      treatment of facial melasma. A number of publications have described the safety
      and efficacy of triple combination cream in over 2000 patients with melasma, some
      of whom were treated for >12 months. In the initial 8-week study, 29% of patients
      experienced complete clearing of melasma by week 8, and 77% were clear or almost
      clear by week 8. Similarly, good results were seen in the two long-term studies,
      with the clear/mild rate ranging from 78% to 84% of patients at month 6 and from
      81% to 94% of patients at month 12. Adverse events were almost always mild in
      severity and typically occurred only at the application site. The primary concern
      for most physicians using corticosteroid-containing products on the face is skin
      atrophy. However, only two cases of skin atrophy were reported across the three
      published studies. Overall, the results of these extensive studies indicate that
      triple combination cream is efficacious in treating melasma and exhibits a safe
      profile with low potential for adverse events.

PMID- 16901183
TI  - Pharmionics in dermatology: a review of topical medication adherence.
AB  - The objective of this article was to review patient adherence to topical
      medications and its relationship to health outcomes in dermatologic disease. To
      this end, MEDLINE searches from January 1966 through June 2006 and EMBASE
      searches from January 1974 through June 2006 were conducted. Relevant human
      efficacy studies, including randomized controlled trials, observational studies,
      and case-control studies, were selected on the basis of the key words
      'compliance,' 'adherence,' 'pharmionics,' 'topical,' 'medication,' or
      'dermatology.' Studies were included and reviewed on the basis of their
      experimental design, controls, and statistical analysis. Analysis revealed that
      suboptimal adherence to topical medications is a common cause of minimal response
      or lack of response to drugs and is linked with poor dermatologic outcomes in
      diseases such as psoriasis, atopic dermatitis, and acne. It is concluded that non
      adherence to topical medications is as common as non-adherence to oral
      medications, and its relationship to poor health outcomes is clear. Several
      barriers to topical medication adherence and predictors of non-adherence are
      similar to those for oral medications, while other barriers and predictors are
      unique to topical medications and the nature of dermatologic disease. Further
      studies of effective interventions to increase adherence are necessary to improve
      health outcomes in dermatology.

PMID- 16901184
TI  - Nephrogenic fibrosing dermopathy: a comprehensive review for the dermatologist.
AB  - Nephrogenic fibrosing dermopathy (NFD) is an acquired, idiopathic, chronic,
      progressive eruption of the skin sometimes accompanied by systemic fibrosis that
      occurs in the context of renal failure. The age of patients with NFD ranges from
      8 to 87 years at the time of onset, with a mean age of 46.4 years. Most cases
      have been reported in the US and Europe, but recently cases have also been
      reported in India. About 175 cases have been noted in a registry established for
      NFD patients. Even in the setting of renal disease, NFD still occurs rarely and
      its cause is unknown. Patients present with hard, indurated, sometimes peau
      d'orange plaques. They often show a distinctive physical appearance, with elbows
      and knees angled inward, and most patients complain of a loss of range of motion.
      Histology demonstrates thickened collagen bundles with surrounding clefts, mucin,
      and a proliferation of fibroblasts and elastic fibers, sometimes with reticular,
      dermal, large epithelioid or stellate spindle cells. Fibrosis of NFD can affect
      the internal organs and thus the term nephrogenic systemic fibrosis has been used
      by some analysts to describe this fibrosing process. The fibrosis of NFD appears
      to be due to the effects of a cell referred to as the circulating fibrocyte. Rare
      cases of partial-to-complete spontaneous resolution have been reported in the
      absence of specific therapy. Treatments yield inconsistent results and include
      restoration of renal function, extracorporeal photopheresis, photodynamic
      therapy, high-dose intravenous immunoglobulin, and other immunosuppressive
      therapies.

PMID- 16901185
TI  - The role of antimalarials in the exacerbation of psoriasis: a systematic review.
AB  - OBJECTIVE: To critically review the body of literature that refutes or supports
      the role of antimalarials in the exacerbation of psoriasis. METHODS: MEDLINE,
      EMBASE, and the Cochrane Central Register of Controlled Trials were reviewed to
      identify English-language publications from 1966-2005 examining the role of
      antimalarials in the exacerbation of psoriasis. A total of 374 articles were
      identified, of which 32 studies met the inclusion criteria. All available
      clinical trials or reported cases of the use of antimalarials for patients with
      psoriasis were included. Data from clinical studies were summarized according to
      the level of evidence and the outcome of the study. Data were entered into a
      standardized data extraction form by two independent reviewers. RESULTS AND
      CONCLUSION: No randomized trial evidence was found. Only one cohort study was
      available for review. A total of 31 case series and case reports were obtained.
      There is no strong evidence to refute or support the role of antimalarials in the
      exacerbation of psoriasis. Controlled trials of antimalarial therapy and its
      effect on psoriasis are warranted.

PMID- 16901186
TI  - Nail penetration of sertaconazole with a sertaconazole-containing nail patch
      formulation.
AB  - BACKGROUND AND OBJECTIVE: Sertaconazole, an imidazole antifungal drug, has been
      proven to have broad and potent antifungal activity. In the present study, the
      pharmacokinetics of sertaconazole nail patches, developed for treatment of
      onychodystrophy and onychomycosis, were investigated in healthy volunteers. The
      objective of the study was to investigate the penetration of sertaconazole into
      the nail and plasma and the residual sertaconazole concentration in patches after
      1 week of application onto the nails. METHODS: In a double-blind study, 16
      healthy adults were treated with a 2.2 cm2 nail patch containing sertaconazole
      3.63 mg and another patch containing no antifungal agent, which were placed on
      the left and right thumbnail of each subject, respectively (or vice versa), in a
      randomized order. The treatment period was 6 weeks and the patches were replaced
      weekly. Nail clippings, used nail patches, and blood samples were investigated to
      determine sertaconazole concentrations. RESULTS: Sertaconazole was detected in
      all sertaconazole-treated nail samples with mean concentrations of >100 microg/g,
      which exceeds the minimum inhibitory concentrations (MICs) for all relevant fungi
      in this context. Measurements of the residual dose in the patches suggested that
      16-71% of the active ingredient had penetrated into the nail. No plasma
      sertaconazole concentrations could be detected. CONCLUSION: By virtue of their
      positive influence (occlusion) on water and lipid metabolism in dystrophic nails,
      nail patches should have beneficial therapeutic effects in onychodystrophic
      conditions. Addition of the antifungal agent sertaconazole adds broad-spectrum
      antimicrobial activity. In this study, the concentrations of sertaconazole in the
      nails were shown to be well above the MIC values for pathogenic fungi relevant to
      onychomycosis. No systemic absorption of the active ingredient was detectable,
      which should exclude unwanted systemic effects of the drug.

PMID- 16901187
TI  - Increased hair shedding may be associated with the presence of Pityrosporum
      ovale.
AB  - BACKGROUND AND OBJECTIVE: Although the available data show that hair loss is an
      important cosmetic problem worldwide, the pathogenesis of common hair shedding is
      not fully understood. The aim of this study was to evaluate the association
      between hair shedding and cutaneous Malassezia infection. Malassezia fungi have
      been the suspected cause of dandruff for more than a century. Previously referred
      to as Pityrosporum ovale or P. orbiculare, these fungi are now known to consist
      of at least seven species. METHODS: Over a 4-year period, we obtained 300 hair
      samples from medical students. Based on the clinical history and a hair-pull
      test, the participants were divided into two groups: normal subjects and subjects
      with hair shedding. The students' scalp skin was gently scraped, smeared on a
      slide, colored by methylene blue, and observed under 10x magnification. RESULTS:
      All participants who had positive smears with >or=3 P. ovale organisms per low
      power microscopic field (10x) were defined as 'carriers.' Seventy-six percent of
      students were Malassezia carriers. The prevalence of positive smears was
      significantly higher among subjects with hair shedding than among normal subjects
      (89.92% vs 9.52%, p<0.001). Furthermore, participants with positive smears had a
      significantly higher frequency of hair loss complaints and positive hair-pull
      tests. CONCLUSION: The proportion of subjects who were carriers of Malassezia
      yeasts was significantly higher in the group with hair shedding, and our results
      therefore raise the possibility of a relationship between this unicellular
      organism and hair loss. Our study findings should be explored in a larger series
      of patients.

PMID- 16901188
TI  - Granulomatous cutaneous centrofacial and meningocerebral amebiasis.
AB  - A 7-year-old, otherwise healthy Peruvian boy presented with a 3-month history of
      an indurated centrofacial plaque. Histologic examination revealed a granuloma
      containing free-living amebae tentatively identified as Balamuthia mandrillaris.
      The patient failed to respond to tentative treatment. He was admitted to the
      intensive care unit 7 months later with neurologic manifestations of
      granulomatous amebic encephalitis, which proved fatal. The difficulty in
      diagnosing this rare presentation of cutaneous amebiasis, the challenge of
      treating the condition, and the morbidity and high mortality associated with
      cerebral involvement are discussed.

PMID- 16901189
TI  - Cutaneous metastasis of renal cell carcinoma.

PMID- 16901190
TI  - Mental disorders of old age, part 3: the more or less normal psychology of aging.

PMID- 16901191
TI  - The case for alcohol in the primary prevention of dementia: abstinence may be bad
      for your health!

PMID- 16901192
TI  - Flat, asymmetrical pigmented patch on back: patient reports substantial sun
      exposure.

PMID- 16901193
TI  - Heart failure update: treatment of heart failure with a normal left ventricular
      ejection fraction in the elderly.
AB  - Heart failure (HF) affects approximately 5 million persons in the United States;
      more than 550,000 new cases of HF are reported each year. Prevalence of HF with a
      normal left ejection fraction increases with age and is higher in older women
      than older men. Both underlying and precipitating causes of HF should be treated
      when possible. Hypertension, especially isolated systolic hypertension, should be
      treated with diuretics, ACE inhibitors, and beta blockers. Myocardial ischemia
      should be treated with nitrates and beta blockers. Anemia should be treated, as
      should hyperthyroidism, hypothyroidism, and obstructive sleep apnea. Use of
      inappropriate drugs, such as nonsteroidal anti-inflammatory drugs, should be
      avoided. Coronary revascularization should be performed in selected individuals.

PMID- 16901194
TI  - The frontal/subcortical dementias: common dementing illnesses associated with
      prominent and disturbing behavioral changes.
AB  - Although the most common cause of dementia is Alzheimer's disease, many other
      common dementing illnesses in the elderly affect the frontal cortex and
      associated subcortical structures and present with very different symptoms. In
      general, these illnesses are not detected with typical bedside screening or with
      conventional dementia assessment tools, such as the Mini Mental State Exam. These
      illnesses are associated with prominent and disturbing behavioral changes, as
      well as difficulties with "higher-order" cognitive functions, such as planning
      and judgment. Common causes of frontal/subcortical dementia include vascular
      dementia, frontotemporal dementia, alcoholic dementia, dementia due to AIDS, and
      a number of movement disorders. Familiarity with this clinical picture is
      essential for recognition, diagnosis, and management of these illnesses, and for
      working with families and caregivers.

PMID- 16901195
TI  - Electrophoretic prefractionation: new commercial tools from an old concept.

PMID- 16901198
TI  - Sixth Annual Meeting on Proteomic Sample Preparation, part of the second annual
      Getting Optimized Targets Summit: 24-25 April 2006, Cambridge Healthtech
      Institute, MA, USA.

PMID- 16901199
TI  - Photoaffinity labeling combined with mass spectrometric approaches as a tool for
      structural proteomics.
AB  - Protein chemistry, such as crosslinking and photoaffinity labeling, in
      combination with modern mass spectrometric techniques, can provide information
      regarding protein-protein interactions beyond that normally obtained from protein
      identification and characterization studies. While protein crosslinking can make
      tertiary and quaternary protein structure information available, photoaffinity
      labeling can be used to obtain structural data about ligand-protein interaction
      sites, such as oligonucleotide-protein, drug-protein and protein-protein
      interaction. In this article, we describe mass spectrometry-based photoaffinity
      labeling methodologies currently used and discuss their current limitations. We
      also discuss their potential as a common approach to structural proteomics for
      providing 3D information regarding the binding region, which ultimately will be
      used for molecular modeling and structure-based drug design.

PMID- 16901200
TI  - Effects of preanalytical variables on peptide and protein measurements in human
      serum and plasma: implications for clinical proteomics.
AB  - There is a wealth of knowledge in the field of in vitro diagnostics with regard
      to preanalytical variables and their impact on the determination of peptide and
      protein analytes in human serum and plasma. This information is applicable to
      clinical proteomics investigations, which utilize the same sample types. Studies
      have demonstrated that the majority of variations and errors in in vitro
      diagnostics seem to occur in the preanalytical phase prior to specimen analysis.
      Preanalytical processes include study design, compliance of the subjects
      investigated, compliance of the technical staff in adherence to protocols, choice
      of specimens utilized and sample collection and processing. These variables can
      have a dramatic impact on the determination of analytes and can affect result
      outcomes, reproducibility and the validity of investigations. By drawing
      analogies to in vitro diagnostics practices, specific variables that are likely
      to impact the results of proteomics studies can be identified. Recognition of
      such variables is the first step towards their understanding and, eventually,
      controlling their impact. In this article, we will review preanalytical
      variables, provide examples for their effects on the determination of distinct
      peptides and proteins and discuss potential implications for clinical proteomics
      investigations.

PMID- 16901201
TI  - Embryonic stem cell proteomics.
AB  - Human embryonic stem cells potentially represent an unlimited source of cells and
      tissues for regenerative medicine. Understanding signaling events that drive
      proliferation and specialization of these cells into various differentiated
      derivatives is of utmost importance for controlling their behavior in vitro.
      Major progress has been made in unraveling these signaling events with large
      scale studies at the transcriptional level, but analysis of protein expression,
      interaction and modification has been more limited, since it requires different
      strategies. Recent advances in mass spectrometry-based proteomics indicate that
      proteome characterization can contribute significantly to our understanding of
      embryonic stem cell biology. In this article, we review mass spectrometry-based
      studies of human and mouse embryonic stem cells and their differentiated progeny,
      as well as studies of conditioned media that have been reported to support self
      renewal of the undifferentiated cells in the absence of the more commonly used
      feeder cells. In addition, we make concise comparisons with related transcriptome
      profiling reports.

PMID- 16901202
TI  - C. elegans: an invaluable model organism for the proteomics studies of the
      cholesterol-mediated signaling pathway.
AB  - With the availability of its complete genome sequence and unique biological
      features relevant to human disease, Caenorhabditis elegans has become an
      invaluable model organism for the studies of proteomics, leading to the
      elucidation of nematode gene function. A journey from the genome to proteome of
      C. elegans may begin with preparation of expressed proteins, which enables a
      large-scale analysis of all possible proteins expressed under specific
      physiological conditions. Although various techniques have been used for
      proteomic analysis of C. elegans, systematic high-throughput analysis is still to
      come in order to accommodate studies of post-translational modification and
      quantitative analysis. Given that no integrated C. elegans protein expression
      database is available, it is about time that a global C. elegans proteome project
      is launched through which datasets of transcriptomes, protein-protein interaction
      and functional annotation can be integrated. As an initial target of a pilot
      project of the C. elegans proteome project, the cholesterol-mediated signaling
      pathway will be an excellent example since, like in other organisms, it is one of
      the key controlling pathways in cell growth and development in C. elegans. As
      this field tends to broaden to functional proteomics, there is a high demand to
      develop the versatile proteome informatics tools that can mange many different
      data in an integrative manner.

PMID- 16901203
TI  - Studying multiple protein profiles over time to assess biomarker validity.
AB  - Protein profile analysis is increasingly used for identification of disease
      biomarkers. The approaches vary from surface-enhanced laser desorption/ionization
      to protein arrays. Newer platforms are constantly being developed. Almost all are
      based on matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry and are often coupled with sophisticated software tools. Protein
      profiling has been applied to a variety of samples including plasma, urine,
      cerebrospinal fluid, saliva and solid tissue. This article focuses on those
      instances where it is possible to obtain sequential samples from the same
      individual. In the authors use of a profile method, many protein changes with
      highly significant correlations to disease have been found. The main challenge
      lies in the validation of the marker to demonstrate its adequacy for use in the
      clinical setting. The latter requires a methodology that is robust and amenable
      to high-throughput. One problem is that interindividual variability among the
      healthy population can mask major changes that occur on an intraindividual basis.
      Often, a large change for an individual may remain within the range of healthy
      individuals. Thus, one strategy to optimize biomarker discovery is to examine
      serial samples from a given individual, where a disease biomarker is established
      by comparison with the individual's own baseline sample. The focus of this review
      is to illustrate the principle and value of serial protein profiling using a
      rapid protein extraction method.

PMID- 16901212
TI  - Data standards: a call to action.
AB  - Access to data is something that every molecular biologist takes for granted
      nowadays, but data alone is of little use unless it is made available in a
      useable form through the development and global uptake of data standards. The
      challenge of standards development has been taken up by grass-roots movements
      working within several different branches of the biomedical research community.
      Many of these initiatives are proving extremely successful; for example, the Gene
      Ontology, which provides a controlled vocabulary for describing the properties of
      gene products, the Microarray Gene Expression Data Society's standards for
      describing microarray experiments, and the emerging standards developed by the
      Proteomics Standards Initiative are gaining broad acceptance. Standards
      development now faces its greatest ever challenge--the integration of diverse
      data types to fulfill the goals of systems biology. Now is the time for the
      communities that are developing these standards, the funding bodies that have
      invested so heavily in high-throughput data generation, and the publishers of
      biomedical research papers to cooperate fully to make the goals of integrated
      data analysis a reality.

PMID- 16901213
TI  - Meeting report: eGenomics: Cataloguing our Complete Genome Collection II.
AB  - This article summarizes the proceedings of the "eGenomics: Cataloguing our
      Complete Genome Collection II" workshop held November 10-11, 2005, at the
      European Bioinformatics Institute. This exploratory workshop, organized by
      members of the Genomic Standards Consortium (GSC), brought together researchers
      from the genomic, functional OMICS, and computational biology communities to
      discuss standardization activities across a range of projects. The workshop
      proceedings and outcomes are set to help guide the development of the GSC's
      Minimal Information about a Genome Sequence (MIGS) specification.

PMID- 16901214
TI  - Evidence standards in experimental and inferential INSDC Third Party Annotation
      data.
AB  - The Third Party Annotation (TPA) project collects and presents high-quality
      annotation of nucleotide sequence. Annotation is submitted by researchers who
      have not themselves generated novel nucleotide sequence. In its first few years,
      the resource has proven to be popular with submitters from a range of biological
      research areas. Central to the project is the requirement for high-quality data,
      resulting from experimental and inferred analysis discussed in peer-reviewed
      publications. The data are divided into two tiers: those with experimental
      evidence and those with inferential evidence. Standards for TPA are detailed and
      illustrated with the aid of case studies.

PMID- 16901215
TI  - Genome Reviews: standardizing content and representation of information about
      complete genomes.
AB  - The Genome Reviews database provides up-to-date, standardized, and
      comprehensively annotated views of the genomic sequence of organisms with
      completely deciphered genomes. Currently, Genome Reviews contains information
      about the genomes of archaea, bacteria, and selected lower eukaryotes. Expansion
      to viral genomes and additional eukaryotes is planned. Genome Reviews is
      available for download in relational and flat file formats. In this paper, the
      rationale behind the creation of Genome Reviews, the approach taken in
      standardizing the data and its representation, and particular issues encountered
      in doing so are described.

PMID- 16901216
TI  - Requirements and standards for organelle genome databases.
AB  - Mitochondria and plastids (collectively called organelles) descended from
      prokaryotes that adopted an intracellular, endosymbiotic lifestyle within early
      eukaryotes. Comparisons of their remnant genomes address a wide variety of
      biological questions, especially when including the genomes of their prokaryotic
      relatives and the many genes transferred to the eukaryotic nucleus during the
      transitions from endosymbiont to organelle. The pace of producing complete
      organellar genome sequences now makes it unfeasible to do broad comparisons using
      the primary literature and, even if it were feasible, it is now becoming uncommon
      for journals to accept detailed descriptions of genome-level features.
      Unfortunately, no database is completely useful for this task, since they have
      little standardization and are riddled with error. Further, the descriptors
      necessary to make full use of these data are generally lacking. Here, I outline
      what is currently wrong and what must be done to make this data useful to the
      scientific community.

PMID- 16901217
TI  - Concept of sample in OMICS technology.
AB  - Fundamental biological processes can now be studied by applying the full range of
      OMICS technologies (genomics, transcriptomics, proteomics, metabolomics, and
      beyond) to the same biological sample. Clearly, it would be desirable if the
      concept of sample were shared among these technologies, especially as up until
      the time a biological sample is prepared for use in a specific OMICS assay, its
      description is inherently technology independent. Sharing a common informatic
      representation would encourage data sharing (rather than data replication),
      thereby reducing redundant data capture and the potential for error. This would
      result in a significant degree of harmonization across different OMICS data
      standardization activities, a task that is critical if we are to integrate data
      from these different data sources. Here, we review the current concept of sample
      in OMICS technologies as it is being dealt with by different OMICS
      standardization initiatives and discuss the special role that the newly formed
      Genomic Standards Consortium (GSC) might have to play in this domain.

PMID- 16901218
TI  - MGED standards: work in progress.
AB  - The Microarray Gene Expression Data (MGED) society is an international
      organization established in 1999 for facilitating sharing of functional genomics
      and proteomics array data. To facilitate microarray data sharing, the MGED
      society has been working in establishing the relevant data standards. The three
      main components (which will be described in more detail later) of MGED standards
      are Minimum Information About a Microarray Experiment (MIAME), a document that
      outlines the minimum information that should be reported about a microarray
      experiment to enable its unambiguous interpretation and reproduction; MAGE, which
      consists of three parts, The Microarray Gene Expression Object Model (MAGE-OM),
      an XML-based document exchange format (MAGE-ML), which is derived directly from
      the object model, and the supporting tool kit MAGEstk; and MO, or MGED Ontology,
      which defines sets of common terms and annotation rules for microarray
      experiments, enabling unambiguous annotation and efficient queries, data analysis
      and data exchange without loss of meaning. We discuss here how these standards
      have been established, how they have evolved, and how they are used.

PMID- 16901219
TI  - The work of the Human Proteome Organisation's Proteomics Standards Initiative
      (HUPO PSI).
AB  - This article describes the origins, working practices and various development
      projects of the HUman Proteome Organisation's Proteomics Standards Initiative
      (HUPO PSI), specifically, our work on reporting requirements, data exchange
      formats and controlled vocabulary terms. We also offer our view of the two
      functional genomics projects in which the PSI plays a role (FuGE and FuGO),
      discussing their impact on our process and laying out the benefits we see as
      accruing, both to the PSI and to biomedical science as a whole as a result of
      their widespread acceptance.

PMID- 16901220
TI  - Experimental standards for high-throughput proteomics.
AB  - Proteome analysis, utilizing high-throughput proteomics approaches, involves
      studying proteins that a whole organism (or specific tissue or cellular
      compartment) expresses under certain conditions. Intrinsic difficulties of these
      studies, as well as the enormous volumes of data they typically produce, make the
      proteome analysis and interpretation very difficult. As with any high-throughput
      approach, proteomics experiments should be carefully designed, analyzed, and
      verified. In addition to computational standards,experimental standards--simple
      and complex mixtures of known proteins--for high-throughput proteomics have to be
      developed and utilized. This article discusses such experimental standards and
      their implementations.

PMID- 16901221
TI  - Establishing reporting standards for metabolomic and metabonomic studies: a call
      for participation.
AB  - Metabolite concentrations in cellular systems are very much dependent on the
      physiological, environmental, and genetic status of an organism and are regarded
      as the ultimate result of cellular regulation, resulting in the visible
      phenotypes. Therefore, the comprehensive analysis of metabolite levels and fluxes
      renders a suitable tool for assessing the degree of perturbation in biological
      systems. Lessons derived from development of other OMICS areas (genomics,
      proteomics, and transcriptomics) have shown that large-scale comparisons and
      interpretations will require the re-use of data over long periods of time and by
      multiple laboratories with different expertise and backgrounds. Reaching this
      goal will require standardization of reporting structures of metabolomic studies
      for journal publication purposes, for regulatory deposition, and for database
      dissemination. An initiative by the Metabolomics Society is presented that aims
      to define important aspects of metabolomic workflows. These include biological
      study designs, chemical analysis, and data processing, as well as the ontologies
      that are necessary in this framework.

PMID- 16901222
TI  - A strategy capitalizing on synergies: the Reporting Structure for Biological
      Investigation (RSBI) working group.
AB  - In this article we present the Reporting Structure for Biological Investigation
      (RSBI), a working group under the Microarray Gene Expression Data (MGED) Society
      umbrella. RSBI brings together several communities to tackle the challenges
      associated with integrating data and representing complex biological
      investigations, employing multiple OMICS technologies. Currently, RSBI includes
      environmental genomics, nutrigenomics and toxicogenomics communities, where
      independent activities are underway to develop databases and establish data
      communication standards within their respective domains. The RSBI working group
      has been conceived as a "single point of focus" for these communities, conforming
      to general accepted view that duplication and incompatibility should be avoided
      where possible. This endeavour has aimed to synergize insular solutions into one
      common terminology between biologically driven standardisation efforts and has
      also resulted in strong collaborations and shared understanding between those in
      the technological domain. Through extensive liaisons with many standards efforts,
      several threads have been woven with the hope that ultimately technology-centered
      standards and their specific extensions into biological domains of interest will
      not only stand alone, but will also be able to function together, as
      interchangeable modules.

PMID- 16901223
TI  - Annotation of environmental OMICS data: application to the transcriptomics
      domain.
AB  - Researchers working on environmentally relevant organisms, populations, and
      communities are increasingly turning to the application of OMICS technologies to
      answer fundamental questions about the natural world, how it changes over time,
      and how it is influenced by anthropogenic factors. In doing so, the need to
      capture meta-data that accurately describes the biological "source" material used
      in such experiments is growing in importance. Here, we provide an overview of the
      formation of the "Env" community of environmental OMICS researchers and its
      efforts at considering the meta-data capture needs of those working in
      environmental OMICS. Specifically, we discuss the development to date of the Env
      specification, an informal specification including descriptors related to
      geographic location, environment, organism relationship, and phenotype. We then
      describe its application to the description of environmental transcriptomic
      experiments and how we have used it to extend the Minimum Information About a
      Microarray Experiment (MIAME) data standard to create a domain-specific extension
      that we have termed MIAME/Env. Finally, we make an open call to the community for
      participation in the Env Community and its future activities.

PMID- 16901224
TI  - FuGE: Functional Genomics Experiment Object Model.
AB  - This is an interim report on the Functional Genomics Experiment (FuGE) Object
      Model. FuGE is a framework for creating data standards for high-throughput
      biological experiments, developed by a consortium of researchers from academia
      and industry. FuGE supports rich annotation of samples, protocols, instruments,
      and software, as well as providing extension points for technology specific
      details. It has been adopted by microarray and proteomics standards bodies as a
      basis for forthcoming standards. It is hoped that standards developers for other
      omics techniques will join this collaborative effort; widespread adoption will
      allow uniform annotation of common parts of functional genomics workflows, reduce
      standard development and learning times through the sharing of consistent
      practice, and ease the construction of software for accessing and integrating
      functional genomics data.

PMID- 16901225
TI  - National Center for Biomedical Ontology: advancing biomedicine through structured
      organization of scientific knowledge.
AB  - The National Center for Biomedical Ontology is a consortium that comprises
      leading informaticians, biologists, clinicians, and ontologists, funded by the
      National Institutes of Health (NIH) Roadmap, to develop innovative technology and
      methods that allow scientists to record, manage, and disseminate biomedical
      information and knowledge in machine-processable form. The goals of the Center
      are (1) to help unify the divergent and isolated efforts in ontology development
      by promoting high quality open-source, standards-based tools to create, manage,
      and use ontologies, (2) to create new software tools so that scientists can use
      ontologies to annotate and analyze biomedical data, (3) to provide a national
      resource for the ongoing evaluation, integration, and evolution of biomedical
      ontologies and associated tools and theories in the context of driving biomedical
      projects (DBPs), and (4) to disseminate the tools and resources of the Center and
      to identify, evaluate, and communicate best practices of ontology development to
      the biomedical community. Through the research activities within the Center,
      collaborations with the DBPs, and interactions with the biomedical community, our
      goal is to help scientists to work more effectively in the e-science paradigm,
      enhancing experiment design, experiment execution, data analysis, information
      synthesis, hypothesis generation and testing, and understand human disease.

PMID- 16901226
TI  - Development of FuGO: an ontology for functional genomics investigations.
AB  - The development of the Functional Genomics Investigation Ontology (FuGO) is a
      collaborative, international effort that will provide a resource for annotating
      functional genomics investigations, including the study design, protocols and
      instrumentation used, the data generated and the types of analysis performed on
      the data. FuGO will contain both terms that are universal to all functional
      genomics investigations and those that are domain specific. In this way, the
      ontology will serve as the "semantic glue" to provide a common understanding of
      data from across these disparate data sources. In addition, FuGO will reference
      out to existing mature ontologies to avoid the need to duplicate these resources,
      and will do so in such a way as to enable their ease of use in annotation. This
      project is in the early stages of development; the paper will describe efforts to
      initiate the project, the scope and organization of the project, the work
      accomplished to date, and the challenges encountered, as well as future plans.

PMID- 16901227
TI  - Development of the Minimum Information Specification for In Situ Hybridization
      and Immunohistochemistry Experiments (MISFISHIE).
AB  - We describe the creation process of the Minimum Information Specification for In
      Situ Hybridization and Immunohistochemistry Experiments (MISFISHIE). Modeled
      after the existing minimum information specification for microarray data, we
      created a new specification for gene expression localization experiments,
      initially to facilitate data sharing within a consortium. After successful use
      within the consortium, the specification was circulated to members of the wider
      biomedical research community for comment and refinement. After a period of
      acquiring many new suggested requirements, it was necessary to enter a final
      phase of excluding those requirements that were deemed inappropriate as a minimum
      requirement for all experiments. The full specification will soon be published as
      a version 1.0 proposal to the community, upon which a more full discussion must
      take place so that the final specification may be achieved with the involvement
      of the whole community.

PMID- 16901228
TI  - Data standards for flow cytometry.
AB  - Flow cytometry (FCM) is an analytical tool widely used for cancer and HIV/AIDS
      research, and treatment, stem cell manipulation and detecting microorganisms in
      environmental samples. Current data standards do not capture the full scope of
      FCM experiments and there is a demand for software tools that can assist in the
      exploration and analysis of large FCM datasets. We are implementing a
      standardized approach to capturing, analyzing, and disseminating FCM data that
      will facilitate both more complex analyses and analysis of datasets that could
      not previously be efficiently studied. Initial work has focused on developing a
      community-based guideline for recording and reporting the details of FCM
      experiments. Open source software tools that implement this standard are being
      created, with an emphasis on facilitating reproducible and extensible data
      analyses. As well, tools for electronic collaboration will assist the integrated
      access and comprehension of experiments to empower users to collaborate on FCM
      analyses. This coordinated, joint development of bioinformatics standards and
      software tools for FCM data analysis has the potential to greatly facilitate both
      basic and clinical research--impacting a notably diverse range of medical and
      environmental research areas.

PMID- 16901229
TI  - Generation Challenge Programme (GCP): standards for crop data.
AB  - The Generation Challenge Programme (GCP) is an international research consortium
      striving to apply molecular biological advances to crop improvement for
      developing countries. Central to its activities is the creation of a next
      generation global crop information platform and network to share genetic
      resources, genomics, and crop improvement information. This system is being
      designed based on a comprehensive scientific domain object model and associated
      shared ontology. This model covers germplasm, genotype, phenotype, functional
      genomics, and geographical information data types needed in GCP research. This
      paper provides an overview of this modeling effort.

PMID- 16901230
TI  - Standard data model representation for taxonomic information.
AB  - The names used by biologists to label the observations they make are imprecise.
      This is an issue as workers increasingly seek to exploit data gathered from
      multiple, unrelated sources on line. Even when the international codes of
      nomenclature are followed strictly the resulting names (Taxon Names) do not
      uniquely identify the taxa (Taxon Concepts) that have been described by
      taxonomists but merely groups of type specimens. A standard data model for
      exchange of taxonomic information is described. It addresses this issue by
      facilitating explicit communication of information about Taxon Concepts and their
      associated names. A representation of this model as a XML Schema is introduced
      and the implications of the use of Globally Unique Identifiers discussed.

PMID- 16901232
TI  - Consideration of future requirements for Raman microbiology as an examplar for
      the ab initio development of informatics frameworks for emergent OMICS
      technologies.
AB  - Raman spectroscopy of single bacteria provides an OMIC-like view of the chemical
      status of individual cells, reporting on metabolism, cell stress and growth, and
      is likely to become a significant tool in environmental and medical microbiology.
      We advocate the early development of integrated data models and informatics
      frameworks, in parallel with the development of Raman hardware and experimental
      protocols, in order to maximize the benefits of this emerging OMIC technology to
      the research community.

PMID- 16901233
TI  - Merging microsatellite data.
AB  - Genotype calling procedures vary from laboratory to laboratory for many
      microsatellite markers. Even within the same laboratory, application of different
      experimental protocols often leads to ambiguities. The impact of these
      ambiguities ranges from irksome to devastating. Resolving the ambiguities can
      increase effective sample size and preserve evidence in favor of disease-marker
      associations. Because different data sets may contain different numbers of
      alleles, merging is unfortunately not a simple process of matching alleles one to
      one. Merging data sets manually is difficult, time-consuming, and error-prone due
      to differences in genotyping hardware, binning methods, molecular weight
      standards, and curve fitting algorithms. Merging is particularly difficult if few
      or no samples occur in common, or if samples are drawn from ethnic groups with
      widely varying allele frequencies. It is dangerous to align alleles simply by
      adding a constant number of base pairs to the alleles of one of the data sets. To
      address these issues, we have developed a Bayesian model and a Markov chain Monte
      Carlo (MCMC) algorithm for sampling the posterior distribution under the model.
      Our computer program, MicroMerge, implements the algorithm and almost always
      accurately and efficiently finds the most likely correct alignment. Common allele
      frequencies across laboratories in the same ethnic group are the single most
      important cue in the model. MicroMerge computes the allelic alignments with the
      greatest posterior probabilities under several merging options. It also reports
      when data sets cannot be confidently merged. These features are emphasized in our
      analysis of simulated and real data.

PMID- 16901231
TI  - Taking the first steps towards a standard for reporting on phylogenies: Minimum
      Information About a Phylogenetic Analysis (MIAPA).
AB  - In the eight years since phylogenomics was introduced as the intersection of
      genomics and phylogenetics, the field has provided fundamental insights into gene
      function, genome history and organismal relationships. The utility of
      phylogenomics is growing with the increase in the number and diversity of taxa
      for which whole genome and large transcriptome sequence sets are being generated.
      We assert that the synergy between genomic and phylogenetic perspectives in
      comparative biology would be enhanced by the development and refinement of
      minimal reporting standards for phylogenetic analyses. Encouraged by the
      development of the Minimum Information About a Microarray Experiment (MIAME)
      standard, we propose a similar roadmap for the development of a Minimal
      Information About a Phylogenetic Analysis (MIAPA) standard. Key in the successful
      development and implementation of such a standard will be broad participation by
      developers of phylogenetic analysis software, phylogenetic database developers,
      practitioners of phylogenomics, and journal editors.

PMID- 16901234
TI  - Coding exon detection using comparative sequences.
AB  - We introduce a new system, called shortHMM, for predicting exons, which predicts
      individual exons using two related genomes. In this system, we build a hidden
      semi-Markov model to identify exons. In the hidden Markov model, we propose joint
      probability models of nucleotides in introns, splice sites, 5'UTR, 3'UTR, and
      intergenic regions by exploiting the homology between related genomes. In order
      to reduce the false positive rate of the hidden Markov model, we develop a
      screening process which is able to identify intergenic regions. We then build a
      classifier by combining the statistics from the hidden Markov model and the
      screening process. We implement shortHMM on human-mouse sequence alignments. The
      source codes are available at < www.stat.purdue.edu/ jingwu/hmm >. Compared to
      TWINSCAN and SLAM, shortHMM is substantially more powerful in identifying AT-rich
      RefSeq exons (8% more AT-rich RefSeq exons were predicted), as well as slightly
      more powerful in identifying RefSeq exons (3-10% more RefSeq exons were
      predicted), at a similar or lower false positive rate, with less computing time
      and with less memory usage. Last, shortHMM is also capable of finding new
      potential exons.

PMID- 16901235
TI  - Designing an A* algorithm for calculating edit distance between rooted-unordered
      trees.
AB  - Tree structures are useful for describing and analyzing biological objects and
      processes. Consequently, there is a need to design metrics and algorithms to
      compare trees. A natural comparison metric is the "Tree Edit Distance," the
      number of simple edit (insert/delete) operations needed to transform one tree
      into the other. Rooted-ordered trees, where the order between the siblings is
      significant, can be compared in polynomial time. Rooted-unordered trees are used
      to describe processes or objects where the topology, rather than the order or the
      identity of each node, is important. For example, in immunology, rooted-unordered
      trees describe the process of immunoglobulin (antibody) gene diversification in
      the germinal center over time. Comparing such trees has been proven to be a
      difficult computational problem that belongs to the set of NP-Complete problems.
      Comparing two trees can be viewed as a search problem in graphs. A* is a search
      algorithm that explores the search space in an efficient order. Using a good
      lower bound estimation of the degree of difference between the two trees, A* can
      reduce search time dramatically. We have designed and implemented a variant of
      the A* search algorithm suitable for calculating tree edit distance. We show here
      that A* is able to perform an edit distance measurement in reasonable time for
      trees with dozens of nodes.

PMID- 16901236
TI  - A general coverage theory for shotgun DNA sequencing.
AB  - The classical theory of shotgun DNA sequencing accounts for neither the placement
      dependencies that are a fundamental consequence of the forward-reverse sequencing
      strategy, nor the edge effect that arises for small to moderate-sized genomic
      targets. These phenomena are relevant to a number of sequencing scenarios,
      including large-insert BAC and fosmid clones, filtered genomic libraries, and
      macro-nuclear chromosomes. Here, we report a model that considers these two
      effects and provides both the expected value of coverage and its variance.
      Comparison to methyl-filtered maize data shows significant improvement over
      classical theory. The model is used to analyze coverage performance over a range
      of small to moderately-sized genomic targets. We find that the read pairing
      effect and the edge effect interact in a non-trivial fashion. Shorter reads give
      superior coverage per unit sequence depth relative to longer ones. In principle,
      end-sequences can be optimized with respect to template insert length; however,
      optimal performance is unlikely to be realized in most cases because of inherent
      size variation in any set of targets. Conversely, single-stranded reads exhibit
      roughly the same coverage attributes as optimized end-reads. Although linking
      information is lost, single-stranded data should not pose a significant assembly
      liability if the target represents predominantly low-copy sequence. We also find
      that random sequencing should be halted at substantially lower redundancies than
      those now associated with larger projects. Given the enormous amount of data
      generated per cycle on pyro-sequencing instruments, this observation suggests
      devising schemes to split each run cycle between twoor more projects. This would
      prevent over-sequencing and would further leverage the pyrosequencing method.

PMID- 16901237
TI  - Pseudoknots in RNA secondary structures: representation, enumeration, and
      prevalence.
AB  - A number of non-coding RNA are known to contain functionally important or
      conserved pseudoknots. However, pseudoknotted structures are more complex than
      orthodox, and most methods for analyzing secondary structures do not handle them.
      I present here a way to decompose and represent general secondary structures
      which extends the tree representation of the stem-loop structure, and use this to
      analyze the frequency of pseudoknots in known and in random secondary structures.
      This comparison shows that, though a number of pseudoknots exist, they are still
      relatively rare and mostly of the simpler kinds. In contrast, random secondary
      structures tend to be heavily knotted, and the number of available structures
      increases dramatically when allowing pseudoknots. Therefore, methods for
      structure prediction and non-coding RNA identification that allow pseudoknots are
      likely to be much less powerful than those that do not, unless they penalize
      pseudoknots appropriately.

PMID- 16901238
TI  - Computation of repetitions and regularities of biologically weighted sequences.
AB  - Biological weighted sequences are used extensively in molecular biology as
      profiles for protein families, in the representation of binding sites and often
      for the representation of sequences produced by a shotgun sequencing strategy. In
      this paper, we address three fundamental problems in the area of biologically
      weighted sequences: (i) computation of repetitions, (ii) pattern matching, and
      (iii) computation of regularities. Our algorithms can be used as basic building
      blocks for more sophisticated algorithms applied on weighted sequences.

PMID- 16901239
TI  - Modeling virus self-assembly pathways: avoiding dynamics using geometric
      constraint decomposition.
AB  - We develop a model for elucidating the assembly pathways by which an icosahedral
      viral shell forms from 60 identical constituent protein monomers. This poorly
      understood process a remarkable example of macromolecular self-assembly occuring
      in nature and possesses many features that are desirable while engineering self
      assembly at the nanoscale. The model uses static geometric and tensegrity
      constraints to represent the driving (weak) forces that cause a viral shell to
      assemble and hold it together. The goal is to answer focused questions about the
      structural properties of a successful assembly pathway. Pathways and their
      properties are carefully defined and computed using computational algebra and
      geometry, specifically state-of-art concepts in geometric constraint
      decomposition. The model is analyzable and refinable and avoids expensive
      dynamics. We show that it has a provably tractable and accurate computational
      simulation and that its predictions are roughly consistent with known information
      about viral shell assembly. Justifications for mathematical and biochemical
      assumptions are provided, and comparisons are drawn with other virus assembly
      models. A method for more conclusive experimental validation involving specific
      viruses is sketched. Overall, the paper indicates a strong and direct, mutually
      beneficial interplay between (a) the concepts underlying macromolecular assembly;
      and (b) a wide variety of established as well as novel concepts from
      combinatorial and computational algebra, geometry and algebraic complexity.

PMID- 16901240
TI  - Utilizing usernames for sex categorization in computer-mediated communication:
      examining perceptions and accuracy.
AB  - As more interpersonal interactions move online, people increasingly get to know
      and recognize one another by their self-selected identifiers called usernames.
      Early research predicted that the lack of available cues in text based computer
      mediated communication (CMC) would make primitive categories such as biological
      sex irrelevant in online interactions. Little is known about the types of
      perceptions people make about one another based on this information, but some
      limited research has shown that questions about gender are the first to be asked
      in online interactions and sex categorization has maintained salience. The
      current project was designed to examine the extent to which individuals might
      include obvious gender information in their usernames, as well as how easily
      gender could be attributed from usernames. Seventy-five coders were asked whether
      or not they could assign 298 people to a sex category based only on their
      username, and then to rate how confident they were in making the attribution.
      Results indicated that coders were fairly inaccurate in making these
      attributions, but moderately confident. Additionally, the results indicated that
      neither women nor men were more accurate in attributing gender from usernames,
      and that neither women nor men tended to use more obvious gender markers in their
      usernames. Additionally, those who did use obvious gender markers in their
      username tended to have less experience with computer chat. The results are
      discussed in conjunction with the limitations of the present investigation, and
      possibilities for future research.

PMID- 16901241
TI  - Using a virtual reality system to study balance and walking in a virtual outdoor
      environment: a pilot study.
AB  - Falls and fall-related injuries are a major problem for elderly persons. Most
      falls occur during walking and turning, and the risk of falling increases when
      attention is diverted to something besides walking. It is often difficult to
      standardize methods for testing balance and fall tendency in a clinically
      relevant setting. We describe the development of a system using a virtual
      environment (VE) to assess how attention demanding and unexpected events
      influence a person's capacity to control balance and movement. The hardware in
      the system consists of a head-mounted display (HMD), a magnetic tracker system,
      and two SGI computers. The software consists of the image generation of the VE
      and the management and visualization of motion tracking data. In a preliminary
      pilot study eight subjects (age 23-80) participated. Each subject walked on a
      normal floor and was visually presented a familiar outdoor environment in the
      HMD. They were exposed to different unexpected events, such as a virtual snowfall
      and tilting of the VE. Disturbances of balance and walking patterns such as
      changes in speed, stride length and balance reactions like slipping were
      observed. Two subjects experienced symptoms of cyber sickness with a SSQ score
      above 25 points. Walking with sensors only did not affect walking time, but in VE
      the subjects generally walked more slowly. Virtual tilting of the environment had
      an impact on balance performance during walking. This effect was not observed
      while the test subjects were walking in a virtual snowfall. The model needs
      further development but may hold a potential for clinical use.

PMID- 16901242
TI  - Time distortion for expert and novice online game players.
AB  - Online game addiction is a new mental disorder. This disorder is difficult to
      describe because of its comprehensive nature. Many online game players have
      problems controlling their playing time. They cannot stop playing a game that
      they enjoy. This research surveyed the past literature on "flow" and time
      disorder theory. A time distortion experiment was conducted. This research
      invited 64 children, teenagers, and young adults to investigate player skill and
      playing time effects on online game break-off. The playing experience and degree
      of time distortion were measured and analyzed. The results showed that both
      novice and expert online game players were subject to time distortion. The
      participants had difficulty breaking off from the game without intrusion by
      others in the real world. This research also suggests eight questions for self
      evaluation for online game addiction.

PMID- 16901243
TI  - Online availability of dextropropoxyphene over time, 2003-2005.
AB  - Online pharmacies are increasingly common, and some of them have been reported to
      inappropriately supply prescription-only medicines. Dextropropoxyphene-containing
      compounds are addictive and frequently implicated in fatalities occurring in the
      United Kingdom. We aimed here at assessing the online availability of
      dextropropoxyphene for purchase over a time-span of 2 years (September 2003
      August 2005). A Google search was run in September 2003 using different sets of
      keywords and the first 100 links identified were thoroughly assessed. In March
      2005, the same e-pharmacies websites identified at baseline were accessed again
      and a Google search using the same sets of keywords previously used was run as
      well. Furthermore, a specialized search with Froogle was run both in March and
      August 2005. Although an illegal practice in most countries, a number of websites
      willing to sell the compound internationally were identified at the time of the
      baseline search. In March 2005, the Google search for vending websites identified
      361,000 links, compared with 40,000 18 months before. Only half of
      dextropropoxyphene vending e-pharmacies were still active by March 2005 but, at
      that point in time, access to Froogle apparently facilitated the task of online
      dextropropoxyphene purchase. By August 2005, however, the same Froogle search
      identified only one link aimed at online dextropropoxyphene shopping. In the
      United Kingdom, dextropropoxyphene-related products will be withdrawn later this
      year but this may have only limited impact on the availability of the compound.
      The emergence of Internet as an unregulated source of controlled substances is an
      important development that may have significant public health implications. This
      issue needs to be dealt with at both international and national level.

PMID- 16901244
TI  - Internet identification and future internet use.
AB  - This paper reports a study investigating the relationship between Internet
      identification and future Internet use. We predict that Internet identification
      is stable over time and that it is predictive of future use. The participants
      were 216 undergraduate students (184 females and 32 males) from five universities
      in the United Kingdom. They completed a questionnaire concerning their use of the
      Internet and a measure of Internet identification at the start of the academic
      year and at the end of the academic year. We found that Internet identification
      measured at the beginning of the academic year was positively related to Internet
      identification measured at the end of the academic year. Furthermore, there was a
      positive relationship between Internet identification and future general Internet
      use and a positive relationship between Internet identification and future
      educational Internet use.

PMID- 16901245
TI  - Effects of Internet use on college students' political efficacy.
AB  - This study examines the relationship between three types of Internet use
      (information, entertainment, and interactive contacts) and two types of political
      efficacy (external and internal) among U.S. college students. Information related
      Internet use and interactive contacts predict college students' internal
      political efficacy. An unexpected finding was that visiting public agency sites
      negatively influenced college students' external political efficacy. This implies
      that the quality of current public sites is below the expectation of college
      students and that respondents who visited those sites might develop political
      cynicism. This study also reveals that online news sites are becoming a primary
      news source for college students.

PMID- 16901246
TI  - Online purchases in an Infocomm sophisticated society.
AB  - This paper presents a preliminary investigation of attitude and intention in
      relation to online shopping in Singapore. Singaporeans display high levels of
      Infocomm proficiency, the result of many intense government initiatives to
      transform the country into an Intelligent Community. Does this Internet embracing
      environment enhance attitude and intention to online shopping? This study
      considers the links between personal consequences, subjective norms, behavioral
      control, and personal innovativeness with attitude and intention among
      Singaporeans. It uses a model based on the Theory of Planned Behavior and makes
      some initial comparisons of its findings with those of existing studies. The
      effects of behavioral control and intention on actual purchase behavior are not
      investigated. Findings permit the tentative proposition that level of Infocomm
      knowledge impacts on attitude and intention.

PMID- 16901247
TI  - Online communication preferences across age, gender, and duration of Internet
      use.
AB  - The present study explored variations in online communication and relationship
      preferences for friends, family, coworkers, and unknown individuals across gender
      (men, women), age (young, middle, late), and duration of Internet use (low,
      medium, high). A total of 174 individuals participated in this study. They were
      divided into two gender (86 men and 88 women), three age (60 young, 60 middle,
      and 54 late) and three Internet use duration (60 low, 58 medium, and 54 high)
      groups. All participants completed several questionnaires that assessed online
      communication and relationship building preferences. Results indicated no
      significant main effect for gender and online communication and relationship
      preferences. The main effect for age was significant for online communication
      with friends and unknown individuals. Young adults indicated their higher
      preferences for online communication with friends and unknown individuals
      compared to middle and late adult age groups. The main effect for duration of
      Internet use was significant for online communication and relationship
      preferences. High Internet users indicated higher scores on online communication
      and relationship building, compared to their counterparts. No significant main
      effects for duration of Internet use were significant on any of the offline
      characteristics. Implications of these findings and their relevance to mental
      health issues and organizational environment were discussed.

PMID- 16901248
TI  - University students' Internet attitudes and Internet self-efficacy: a study at
      three universities in Taiwan.
AB  - This study was conducted to explore university students' attitudes and self
      efficacy toward the Internet. Moreover, the relationships between their attitudes
      and self-efficacy toward the Internet were also investigated. The sample of this
      study included 1,313 students, coming from three universities in Taiwan. It was
      found that male students expressed significantly more positive attitudes than
      females on their "perceived control" of the Internet. The male students also
      revealed better Internet self-efficacy than their female counterparts. Moreover,
      students having more on-line hours per week, in general, displayed more positive
      Internet attitudes and Internet self-efficacy. In addition, students' grade level
      also played an important role in their Internet attitudes; graduate students
      tended to possess more positive Internet attitudes. More importantly, students'
      Internet attitudes were highly correlated with their Internet self-efficacy. The
      results in this study seemed to reveal that students' attitudes toward the
      Internet could be viewed as one of the important indicators for predicting their
      Internet self-efficacy. It is also suggested that some training programs or
      courses may be helpful in improving university students' attitudes and self
      efficacy toward the Internet.

PMID- 16901249
TI  - Massively multiplayer online role-playing game-induced seizures: a neglected
      health problem in Internet addiction.
AB  - As the Internet has become rapidly and widely integrated into society, Internet
      addiction has become a growing psychosocial problem. However, epileptic seizure,
      another out-of-the-ordinary health problem, is often neglected in this regard.
      Ten patients who experienced epileptic seizures while playing the newest genre of
      electronic games -- Massively Multiplayer Online Role-Playing Games (MMORPGs) --
      were investigated. Patients were predominantly male young adults, and most of the
      events were generalized tonic-clonic seizures, myoclonic seizures, and absences.
      These patients should be categorized into idiopathic generalized epilepsies. Even
      though photosensitivity was an important factor, behavioral and higher mental
      activities also seemed to be significant seizure precipitants. Results
      demonstrated that MMORPG-induced seizures were not analogous to the ordinary
      video game-induced seizures. Significantly, an epileptic seizure warning did not
      always appear on the websites of MMORPGs and instructions for the software. While
      the prevalence of MMORPG-induced seizures remains unknown, it may exceed our
      expectations and impact our society. Not only for clinical neurologists but also
      for the primary physicians, educators, sociologists, and global online game
      publishers, there should be an awareness of this special form of reflex seizures
      in order to provide an appropriate health warning to MMORPG players.

PMID- 16901250
TI  - Is severe obesity a form of addiction? Rationale, clinical approach, and
      controlled clinical trial.
AB  - For many, obesity is just a problem of energy input and expenditure: more energy
      input than expenditure. However, the clinical practice and epidemiological data
      clearly show that weight control is more complex than expected by this simple
      equation. This is particularly true in morbid obesity, a form of severe obesity
      in which a person's Body Mass Index (BMI, kg/m(2)) is over 40. If we compare the
      definitions and diagnostic criteria for "dependence" and "addiction" with the
      situation of many severe obese subjects, it is apparent that they match very
      well. Further, different neurological studies confirm this similarity: both
      addiction and obesity patients have a deficiency of dopamine receptors.
      Nevertheless, when we compare many of the actual obesity treatments with the ones
      used in the area of addictions it is possible to find relevant differences:
      obesity treatments neither consider different levels of type and intensity of
      care, nor a multidimensional approach. To overcome these limitations, in this
      paper we propose a bio-psychosocial approach in which the genetic influence (lack
      of dopamine receptors) is matched by psychosocial issues (pressure for thinness
      and diet as main body image dissatisfaction treatment). Further, the paper
      outlines how this approach may influence the treatment options, by focusing both
      on the lessons coming from actual addiction treatment and the opportunities
      offered by virtual reality. Finally, the paper presents and discusses the outcome
      of a controlled trial, based on the proposed approach, including a 6-month follow
      up (211 morbid obese females with a BMI of >40 and a documented history of
      failures.

PMID- 16901251
TI  - Virtual reality exposure therapy: 150-degree screen to desktop PC.
AB  - Virtual reality exposure therapy (VRET) developed using immersive or semi
      immersive virtual environments present a usability problem for practitioners. To
      meet practitioner requirements for lower cost and portability VRET programs must
      often be ported onto desktop environments such as the personal computer (PC).
      However, success of VRET has been shown to be linked to presence, and the
      environment's ability to evoke the same reactions and emotions as a real
      experience. It is generally accepted that high-end virtual environments (VEs) are
      more immersive than desktop PCs, but level of immersion does not always predict
      level of presence. This paper reports on the impact on presence of porting a
      therapeutic VR application for schizophrenia from the initial research
      environment of a semi-immersive curved screen to PC. Presence in these two
      environments is measured both introspectively and across a number of causal
      factors thought to underlie the experience of presence. Results show that the VR
      exposure program successfully made users feel they were "present" in both
      platforms. While the desktop PC achieved higher scores on presence across causal
      factors participants reported they felt more present in the curved screen
      environment. While comparison of the two groups was statistically significant for
      the PQ but not for the IPQ, subjective reports of experiences in the environments
      should be considered in future research as the success of VRET relies heavily on
      the emotional response of patients to the therapeutic program.

PMID- 16901252
TI  - Cybersuicide: review of the role of the internet on suicide.
AB  - The internet as a widespread source of communication is already having a
      significant influence in medicine and psychiatry. Although the internet has great
      potential in psychiatric education, clinical care, and research, its impact on
      social issues should not be underestimated. Firstly, the internet as a means of
      communication may encourage suicidal behavior by depicting ways by which suicide
      may be committed. Secondly, some internet websites may discourage people with
      mental illness from seeking psychiatric help, condone suicide, and forbid entry
      to anyone offering to discourage users from committing suicide. However, the
      internet could be a resource to help a potentially suicidal person get help, and
      can be used to identify those at risk for suicide, communicate with them, and
      potentially prevent suicide. If used appropriately, the internet is a powerful
      communication tool that can be used to benefit suicidal patients.

PMID- 16901253
TI  - Worried and wired: effects of health anxiety on information-seeking and health
      care utilization behaviors.
AB  - Although online health information-seeking has been widely studied and findings
      suggest a variety of motivations behind an individual's health information
      seeking behavior, little is known about how this information influences health
      utilization behaviors. Thus, the current study investigates the relationship
      between online health information seeking and health care utilization such as
      visiting a doctor. Additionally, this project expands the literature by examining
      the moderating role of health anxiety. Results suggest that an individual's level
      of health anxiety moderates the relationship between online health information
      seeking and health care utilization decisions.

PMID- 16901256
TI  - Heightened subjective experience of depression in borderline personality
      disorder.
AB  - Despite the frequent comorbidity of major depression and borderline personality
      disorder (BPD), limited research has examined what effect this comorbidity has on
      the severity, course, and presentation of depression. The purpose of this study
      was to examine whether the severity of major depressive disorder (MDD) in the
      context of comorbid borderline personality disorder (BPD) differs from MDD when
      comorbid BPD is not present and to determine whether different measures of
      depression yield convergent findings. Sixty patients diagnosed with DSM-IV MDD
      participated in this study. Twenty-nine were diagnosed with DSM-IV BPD, while the
      remaining 31 had no Axis II diagnosis. Depression was evaluated with both
      clinician (Hamilton Rating Scale for Depression) and self-report (Beck Depression
      Inventory) ratings. While the two groups were rated as similarly depressed by
      clinicians on the overall rating and the factor scores, the MDD/BPD group
      reported more severe depressive symptoms on the self-report measure. This
      difference was significant even after controlling for clinician-rated severity.
      Gender interacted with diagnosis, males in the BPD group showed the largest
      discrepancies between clinician ratings and self-reports. Posthoc analyses of
      HDRS factors with the BDI showed that the clinicianrated cognitive disturbance
      and retardation factors were correlated with self-rated severity overall. Within
      subgroups, only the retardation factor was correlated with the BDI. Our results
      suggest that while depressed individuals with and without BPD may be rated as
      similarly depressed when assessed with objective rating methods, the subjective
      experience of the depression may be rated as more intense or severe by patients
      with comorbid BPD. The mechanism underlying this effect remains unknown, and
      requires further research.

PMID- 16901257
TI  - Characteristic interpersonal behavior in dependent and avoidant personality
      disorder can be observed within very short interaction sequences.
AB  - We present a behavior observation study of interpersonal behavior in 96 female
      subjects, who had been screened for the presence of dependent, avoidant,
      narcissistic and histrionic personality disorder features. Each subject took part
      in three short role-plays, taken from assertiveness training. Afterwards, both
      the subject and her role-play partner judged, how assertive the subject had been.
      Although observation time was very short, dependent and avoidant subjects could
      be easily identified from their overly submissive behavior in the role-plays.
      Histrionic and narcissistic subjects did not show distinctive interpersonal
      behavior. Contrary to a common belief, higher scores on some personality disorder
      (PD) scales were positively related to cross-situational variability of behavior.
      Results are discussed with regard to their implications for clinical diagnostics,
      therapy and the methodology of personality disorder research in general.

PMID- 16901258
TI  - Self-reported attachment, interpersonal aggression, and personality disorder in a
      prospective community sample of adolescents and adults.
AB  - Anxious and avoidant attachment were assessed in the Children in the Community
      (CIC) Study during adolescence and adulthood using self-report scales developed
      for this prospective study. The convergent and discriminant validity of the new
      CIC attachment scales were evaluated and their stability was assessed across a 17
      year interval. Attachment scales predicted DSM-IV personality disorders in
      theoretically coherent and clinically meaningful ways, especially when
      supplemented with a separate measure of interpersonal aggression. Cluster B and C
      personality disorder symptoms were associated with elevated anxious attachment.
      Avoidant attachment was positively associated with Cluster A symptoms and
      inversely associated with Cluster B and C symptoms. Interpersonal aggression was
      higher in Cluster B symptoms and lower in Cluster C symptoms, thus
      differentiating between these symptom clusters.

PMID- 16901259
TI  - The longitudinal relation between personality disorder symptoms and depression in
      adolescence: the mediating role of interpersonal stress.
AB  - The relation between personality disorder (PD) symptoms, depression, and
      interpersonal stress were examined over 6 months in a sample of 143 adolescents
      from a low-income urban high school. Both self report questionnaires in the full
      sample and structured interviews in a subset of 54 girls indicated the following:
      PD symptoms predicted greater depressive symptoms and interpersonal stress over
      time; PD symptoms were highly stable; depressive symptoms did not predict change
      in PD symptoms over time. Moreover, an integrative model was supported, wherein
      the route by which PD symptoms led to greater depression was via the generation
      of interpersonal stress. These results suggest that adolescents' PD symptoms play
      a destructive role in the construction of interpersonal circumstances during a
      key period for depression onset.

PMID- 16901260
TI  - Treatment utilization and satisfaction: examining the contributions of Axis II
      psychopathology and the Five-Factor Model of personality.
AB  - Numerous studies have demonstrated a link between personality disorders (PDs) and
      increased treatment utilization and decreased satisfaction. However, few studies
      have examined the link between general personality models, such as the Five
      Factor Model (FFM), and these treatment variables. The current study examines the
      role of depression, anxiety, and functioning, PDs, and the FFM in accounting for
      psychiatric treatment utilization and satisfaction with care in two distinct
      clinical samples (n = 99 and 544, respectively). The results suggest that both
      maladaptive personality symptoms and general personality traits are predictive of
      these outcome variables. Importantly, the findings regarding treatment
      utilization replicate across samples and level of personality assessment (i.e.,
      FFM and PDs). It is argued that both types of personality information should be
      included in the initial treatment planning and implementation stages.

PMID- 16901261
TI  - Should self-defeating personality disorder be revisited in the DSM?
AB  - Self-defeating personality disorder (SDPD) was proposed for consideration in the
      DSM-III-R, but was eventually removed from the manual because of the lack of
      evidence to support its validity. Yet, after DSM-IV was published, some studies
      suggested that SDPD may be a viable diagnosis. The purpose of this study was to
      evaluate SDPD's viability as a diagnostic category. Consequently, SDPD's internal
      consistency, comorbidity with other Axis I and II disorders, association with
      psychosocial impairment, and its ability to predict overall impairment in past,
      current, and global levels of functioning beyond other personality disorder
      symptomatology was assessed in 1,200 psychiatric evaluated with the Structured
      Clinical Interview for DSM-IV Personality (Pfohl, Blum, & Zimmerman, 1997).
      Cronbach's alpha for SDPD criteria was 0.61, and item-total correlations ranged
      between 0.22-0.38. There was substantial comorbidity of SDPD with depressive,
      avoidant, and borderline personality disorders, as well as major depression and
      anxiety disorders. The SDPD group did not significantly differ from psychiatric
      controls on multiple measures of psychosocial impairment, global functioning, and
      suicidality. SDPD did not meaningfully add to the prediction of impairment above
      and beyond other measures of Axis II pathology. It is concluded that the data do
      not support the reliability, validity, and utility of the SDPD diagnosis.

PMID- 16901262
TI  - Personality prototypes in eating disorders based on the Big Five model.
AB  - A three factor model of personality pathology was investigated in a clinical
      sample of 335 female eating disordered patients. Cluster analysis of the Big Five
      NEO-FFI scales (Costa & McCrae, 1992) yielded three distinct personality
      profiles, which were consistent with previous studies: (1) a resilient/high
      functioning cluster with no clinical elevations on the NEO-FFI scales; (2) an
      undercontrolled/emotionally dysregulated cluster with elevated scores on the
      Neuroticism scale and low scores on Conscientiousness and Agreeableness; (3) an
      overcontrolled/constricted cluster showing high scores on Neuroticism and
      Conscientiousness and low scores on Openness to Experience. Comparing the three
      personality prototypes with respect to Axis I and Axis II disorders,resilients
      reported systematically less clinical and personality problems than both
      undercontrollers and overcontrollers. Compared to the latter, undercontrollers
      showed more impulsive personality features and behaviors. Finally, cluster
      membership was not clearly associated with eating disorder subtypes, suggesting
      that there is considerable variance in personality features and/or pathology
      within the various eating disorder categories.

PMID- 16901263
TI  - Personality pathology among individuals with a lifetime history of anorexia
      nervosa.
AB  - Anorexia nervosa (AN) appears to be associated with certain personality features.
      The degree to which personality pathology persists after the acute phase of
      illness is unclear. This study aimed to investigate personality pathology in a
      large sample (n = 153) of women with histories of AN using the Dimensional
      Assessment of Personality Pathology (DAPP) and to evaluate the persistence of
      pathological personality features by comparing women with acute (n = 83) and
      remitted AN (n = 55). Women with AN demonstrated high levels of emotional
      dysregulation, social inhibition and compulsivity relative to age-matched healthy
      women (n = 124). Identity problems, intimacy problems and schizotypal features
      were highlighted as important. The same 14 pathological personality dimensions
      were significantly elevated in both ill and remitted participants, though
      remitted individuals' scores were reduced on 4 of the subscales. These results
      indicate that pathological personality features in AN are persistent traits,
      although some features may become exaggerated in the acute phase.

PMID- 16901264
TI  - Can angiogenesis be exploited to improve stroke outcome? Mechanisms and
      therapeutic potential.
AB  - Recent developments in our understanding of the pathophysiological events that
      follow acute ischaemic stroke suggest an important role for angiogenesis which,
      through new blood vessel formation, results in improved collateral circulation
      and may impact on the medium-to-long term recovery of patients. Future treatment
      regimens may focus on optimization of this process in the ischaemic boundary
      zones or 'penumbra' region adjacent to the infarct, where partially affected
      neurons exposed to intermediate perfusion levels have the capability of survival
      if perfusion is maintained or normalized. In this review, we present evidence
      that angiogenesis is a key feature of ischaemic stroke recovery and neuronal post
      stroke re-organization, examine the signalling mechanisms through which it
      occurs, and describe the therapeutic potential of treatments aimed at stimulating
      revascularization and neuroprotection after stroke.

PMID- 16901265
TI  - SREBP-2 positively regulates transcription of the cholesterol efflux gene, ABCA1,
      by generating oxysterol ligands for LXR.
AB  - Cholesterol accumulation and removal are regulated by two different transcription
      factors. SREBP-2 (sterol-regulatory-element-binding protein-2) is best known to
      up-regulate genes involved in cholesterol biosynthesis and uptake, whereas LXR
      (liver X receptor) is best known for up-regulating cholesterol efflux genes. An
      important cholesterol efflux gene that is regulated by LXR is the ATP-binding
      cassette transporter, ABCA1 (ATP-binding cassette transporter-A1). We have
      previously shown that statin treatment down-regulated ABCA1 expression in human
      macrophages, probably by inhibiting synthesis of the LXR ligand 24(S),25
      epoxycholesterol. However, it was subsequently reported that ABCA1 expression is
      down-regulated by SREBP-2 through binding of SREBP-2 to an E-box element in
      ABCA1's proximal promoter. As statin treatment induces SREBP-2 activation, this
      may provide an alternative explanation for the statin-mediated down-regulation of
      ABCA1. In the present study, we employed a set of CHO (Chinese-hamster ovary)
      mutant cell lines to investigate the role of SREBP-2 in the regulation of ABCA1.
      We observed increased ABCA1 mRNA levels in SREBP-2-overexpressing cells and
      decreased levels in cells lacking a functional SREBP-2 pathway, which were
      restored when the SREBP-2 pathway was reinstated. Moreover, ABCA1 gene expression
      was positively associated with synthesis of 24(S),25-epoxycholesterol in these
      cell lines. In studies using a human ABCA1 promoter reporter assay, mutation of
      the E-box motif had a similar response as the wild-type construct to either
      statin treatment or addition of 24(S),25-epoxycholesterol. By contrast, these
      responses were completely ablated when the DR4 element to which LXR binds was
      mutated. These results support the idea that 24(S),25-epoxycholesterol and statin
      treatment influence ABCA1 transcription via supply of an LXR ligand and not
      through an SREBP-2/E-box-related mechanism. In addition, our results indicate a
      critical role of SREBP-2 as a positive regulator of ABCA1 gene expression by
      enabling the generation of oxysterol ligands for LXR.

PMID- 16901266
TI  - Heparan sulfate 6-O-endosulfatases: discrete in vivo activities and functional co
      operativity.
AB  - HS (heparan sulfate) is essential for normal embryonic development. This
      requirement is due to the obligatory role for HS in the signalling pathways of
      many growth factors and morphogens that bind to sulfated domains in the HS
      polymer chain. The sulfation patterning of HS is determined by a complex
      interplay of Golgi-located N- and O-sulfotransferases which sulfate the heparan
      precursor and cell surface endosulfatases that selectively remove 6-O-sulfates
      from mature HS chains. In the present study we generated single or double knock
      out mice for the two murine endosulfatases mSulf1 and mSulf2. Detailed structural
      analysis of HS from mSulf1-/- fibroblasts showed a striking increase in 6-O
      sulfation, which was not seen in mSulf2-/- HS. Intriguingly, the level of 6-O
      sulfation in the double mSulf1-/-/2-/- HS was significantly higher than that
      observed in the mSulf1-/- counterpart. These data imply that mSulf1 and mSulf2
      are functionally co-operative. Unlike their avian orthologues, mammalian Sulf
      activities are not restricted to the highly sulfated S-domains of HS. Mitogenesis
      assays with FGF2 (fibroblast growth factor 2) revealed that Sulf activity
      decreases the activating potential of newly-synthesized HS, suggesting an
      important role for these enzymes in cell growth regulation in embryonic and adult
      tissues.

PMID- 16901267
TI  - Effects of seasonal and physiological variations on the serum chemistry, vitamins
      and thyroid hormone concentrations in sheep.
AB  - The aim of this study was to investigate the possible effects of the reproductive
      status and seasonal variations on the serum chemistry and vitamin status and
      their relationships with the thyroid hormones in Sakiz-Awassi crossbreed sheep.
      The sheep (n = 34) were divided into two groups. The first group (n = 22) was
      mated; the second group (n = 12) was not mated. Their serum samples were
      collected four times a year at the each season and under reproductive status. The
      periods are 1, early pregnancy (October); 2, late pregnancy (January); 3,
      lactation (April); and 4, dry season (July). The results of this study indicated
      that (1) total protein (TP), globulin, cholesterol, creatinine, uric acid and
      T4/T3 vary with reproductive status but not seasonal variations; (2) alanine
      aminotransferase, T4, fT4 concentrations in serum vary only with reproductive
      status; (3) the urea, creatine kinase, lactate dehydrogenase, alkaline
      phosphatase, aspartate aminotransferase, amylase, albumin, triglyceride, VLDL,
      Vit A-E, T3 and fT3 concentration could vary with both reproductive status and
      seasonal variations; (4) the glucose, gamma-glutamyl transpeptidase, folate
      concentrations were altered neither season of the year nor the reproductive
      status; (5) a single reference interval for folate, gamma-glutamyl transpeptidase
      (GGT), glucose, TP, globulin, cholesterol, creatinine, uric acid and T4/T3 can be
      used for both mated and non-mated sheep because of no differences were found due
      to the reproductive status. Taking the results together suggests that
      reproductive status and seasonal variations have to be taken into consideration
      for a correct interpretation of the serum chemistry values of sheep. Nutritional
      supplements are required for sheep during certain periods to avoid a decline of
      their performance, which would then represent consequent economic, loses.

PMID- 16901268
TI  - Effects of age and reproductive stage on certain serum biochemical parameters of
      chios sheep under greek rearing conditions.
AB  - The aim of the present study was to determine the normal ranges of the most
      commonly used serum biochemical parameters of sheep reared under Greek breeding
      conditions, as well as to test for the effects of the age and reproductive status
      of the animals on the normal values of these parameters. In total, 200 clinically
      healthy Chios sheep from 10 farms were used in the experiment. For the
      determination of the effect of age 150 sheep were assigned in three groups. Group
      A consisting of 50 lambs aged 2-6 months (mean +/- SD: 4.15 +/- 1.08), group B of
      50 non-pregnant ewes into lactation aged 1-3 years (mean +/- SD: 2.12 +/- 0.86)
      and group C of 50 non-pregnant ewes into lactation aged more than 3 years (mean
      +/- SD: 5.98 +/- 1.66). For evaluating the effect of reproductive status 50
      pregnant ewes in dry period were used, 15-30 days before the expected day of
      lambing (group D), along with the 100 non-pregnant ewes into lactation of groups
      B and C (group E). Blood sampling was performed once, in dry ewes from December
      to January, and in lambs and lactating ewes from March to May. The results showed
      that of the 14 biochemical parameters determined in serum, six were significantly
      affected by the age and eight by the reproductive stage of the animals.

PMID- 16901269
TI  - Intestinal cryptosporidiosis in turkeys in Iran.
AB  - Naturally occurring cryptosporidiosis is reported in turkey poults suffering from
      diarrhoea and unthriftness in Iran. Histological and ultrastructural studies
      revealed high number of Cryptosporidium developmental stages mainly located in
      the mid and terminal portions of small intestine of the poults. Other portions of
      the intestinal tract were less frequently infected. Oocyst shedding was detected
      only in 29% of the histologically positive birds. Based on host species, clinical
      signs, pathology and tissue location of the parasites, Cryptosporidium
      meleagridis was most likely responsible for these infections. This parasite was
      also reported recently in a child with diarrhoea in Iran.

PMID- 16901270
TI  - Purkinje cell apoptosis in arabian horses with cerebellar abiotrophy.
AB  - Purkinje cerebellar cells were studied in three Arabian horses aged between 6 and
      8 months with clinical disorders in their movements, tremors and ataxia; the
      occurrence of apoptosis in this cell population was investigated by the (terminal
      deoxynucleotidyl transferase biotin-dUTP nick-end labelling (TUNEL) method. Both
      optical and electron microscopical images showed a scant number of Purkinje
      cells, most of them with morphological features of apoptosis such as condensation
      of the nucleus and cytoplasm as well as segregation and fragmentation of the
      nucleus into apoptotic bodies. The TUNEL technique revealed a substantial number
      (65%) of positive immunoreactive Purkinje cells.

PMID- 16901271
TI  - Lameness in a dog caused by thoracic wall invasion by a pulmonary neoplasm.
AB  - A 12-year-old fox-terrier dog presented with forelimb lameness of 3-weeks
      duration. Ultrasonography revealed a mass within the thoracic wall and osteolysis
      of the left third rib. A squamous cell carcinoma was diagnosed by cytological
      examination of an ultrasound-guided fine needle aspirate of this mass. As a
      result of the diagnosis of neoplasia, the dog was euthanatized. Necropsy revealed
      a solitary expansile mass within the left cranial lung lobe, and a mass within
      the adjacent thoracic wall. Thickening of the pleura between the two masses was
      visible, although adhesions were not present. Histology of both masses revealed a
      well-differentiated squamous cell carcinoma. To the authors' knowledge, this is
      the first detailed description of direct invasion of the thoracic wall by a
      canine lung tumour.

PMID- 16901272
TI  - Subcutaneous haemangiosarcoma in a cockatiel (Nymphicus hollandicus).
AB  - An ulcerated, 1 x 0.5 cm, subcutaneous mass on the craniolateral aspect of the
      right tibiotarsus of a 4-year-old male cockatiel was removed. Histologically, the
      neoplasm was non-encapsulated, infiltrative and composed of irregular vascular
      channels lined by branching and variably sized spindle-shaped cells with large
      vesicular nuclei, prominent nucleoli and rare mitoses. Surrounding these vascular
      channels were fibroblasts and mixed inflammatory cells. Neoplastic cells had
      diffuse immunoreactivity to factor VIII supporting a diagnosis of
      haemangiosarcoma.

PMID- 16901273
TI  - Primary erythrocytosis in a Japanese black calf: a case report.
AB  - An 8-month-old Japanese Black heifer with severe erythropoietic symptoms was
      subjected to clinical, histological and cytological examinations. During the 1
      month clinical observation period, severe increases in RBC count, packed cell
      volume and haemoglobin concentration were observed. The plasma erythropoietin
      (Epo) concentration of the heifer (20.7 mIU/ml) was similar to that observed in
      normal control heifers. Blood gas examinations of the arterial and venous blood
      revealed low levels of partial pressure O(2) (PaO(2)), partial pressure CO(2)
      (PaCO(2)) and O(2) saturation (SaO(2)), while the blood pH was within the normal
      range. Gross lesions could not be detected. However, microscopic observation
      revealed severe proliferation of erythroblasts in the bone marrow and in the
      spleen without evidence of neoplastic changes. Based on these clinical and
      pathological examinations, we diagnosed the heifer as being the first case of
      primary erythrocytosis in Japanese Black cattle.

PMID- 16901274
TI  - Pharmacokinetics of moxifloxacin in rabbits after intravenous, subcutaneous and a
      long-acting poloxamer 407 gel formulation administration.
AB  - The pharmacokinetics (PK) of moxifloxacin in healthy white New Zealand rabbits
      was studied following intravenous (IV) and subcutaneous (SC) administration
      routes as well as a SC long-acting poloxamer 407 gel formulation (SC-P407).
      Moxifloxacin concentrations were determined by high-performance liquid
      chromatography assay with fluorescence detection. Mean half-life for IV, SC and
      SC-P407 routes was 2.15, 5.41 and 11.09 h. Clearance value after IV dosing was
      0.78 l/kg/h. After SC administration, the mean absolute bioavailability was 117%
      and the C(max) was 1.61 +/- 0.49 mg/l. After SC-P407 administration, the
      bioavailability was 44% and the C(max) 1.83 was +/-0.62 mg/l. No adverse effects
      were observed in any of the rabbits following IV, SC and SC-P407 administration
      of moxifloxacin. Minimal inhibitory concentrations of moxifloxacin against
      different strains of Staphylococcus aureus from different european countries were
      used to compute the main pharmacodynamic (PD) surrogate markers of efficacy. The
      high tolerability of this SC-P407 formulation and the favourable PK behaviour
      such as the long half-life, acceptable bioavailability and excellent PK-PD ratios
      achieved indicate that it is likely to be effective in rabbits.

PMID- 16901275
TI  - Long-term follow-up of blood lead levels and haematological and biochemical
      parameters in heifers that survived an accidental lead poisoning episode.
AB  - Four of 10 heifers that survived an episode of lead poisoning caused by an old
      broken battery in the pasture were periodically monitored from days 14 to 205
      after the episode, with the aim of (i) determining the time-course of lead
      clearance from blood; and (ii) assessing whether the exposed cattle showed
      changes in haematological parameters or serum markers of hepatic and renal
      function (e.g. serum creatinine level) that might be useful as indicators of
      subclinical toxicity. On the first sampling day, lead levels in blood varied
      between 0.478 and 0.758 mg/l. The half-life of lead in blood was rather variable,
      ranging from 68 to 266 days. Despite the high blood lead levels, no significant
      changes were detected in haematological parameters or hepatic/renal markers, all
      of which remained within normal ranges. In conclusion, these cattle that survived
      an episode of lead poisoning may constitute a risk for human consumers, but do
      not appear to have suffered severe health consequences themselves.

PMID- 16901276
TI  - Changes in MMP-2 and -9 activity and MMP-8 reactivity after amphotericin B
      induced synovitis and treatment with bufexamac.
AB  - The objective here was to evaluate the acute effects of induced arthritis on
      synovial fluid (SF) levels of matrix metalloproteinases (MMP) -2, -8 and -9 in
      horses. To evaluate MMP-2 and -9 activities and the effect of non-steroidal anti
      inflammatory drug (NSAID) bufexamac during remission from acute arthritis.
      Aseptic arthritis was induced in 24 Standardbred horses using 20 mg of
      amphotericin B as a single intra-articular (IA) injection in the right
      intercarpal joint. After 1 week and 2 weeks, horses were treated intra
      articularly with 10, 20, or 40 mg of bufexamac suspension or with sterile saline
      solution as control. SF was sampled prior to induction and at weekly intervals
      for 5 weeks. Fluids were evaluated for MMP-2 and MMP-9 activity by gelatin
      zymography or for MMP-8 immunoreactivity by Western Blotting. IA injection of
      amphotericin B consistently resulted in significant increase in the
      immunoreactivity of MMP-8 and activity of both the latent and the active forms of
      MMP-2 and -9, among which the active form of MMP-2 increased the most. MMP-9
      levels declined to pre-induction levels within 2 weeks, whereas levels of MMP-2
      remained still high after 5 weeks. Treatment with bufexamac did not significantly
      affect levels of gelatinolytic MMP. Results suggest that after acute arthritis of
      horses, elevated MMP activity is present in the joint, for several weeks, to a
      degree that could promote cartilage degradation, and treatment with the NSAID
      bufexamac is not likely to affect that. Furthermore, analysing levels of MMP-9
      activity and especially levels of active forms of MMP-2 activity may be valuable
      to predict the time of occurrence of arthritis in horses.

PMID- 16901277
TI  - Antioxidant status of faeces of captive black rhinoceros (Diceros bicornis) in
      relation to dietary tannin supplementation.
AB  - In context with the frequent observations of excessive iron (Fe) storage in
      captive black rhinoceroses (Diceros bicornis), it has been suggested that both an
      excessive dietary Fe content and a lack of dietary Fe-chelating substances, such
      as tannins, is the underlying cause. Therefore, studies on the effects of tannin
      supplementation to captive diet are warranted. Six captive rhinoceroses were fed
      their normal zoo diet (N), and a similar diet supplemented with either tannic
      acid (T, hydrolysable tannin) or quebracho (Q, condensed tannins), and the total
      antioxidant capacity (TAC) was measured as mmol Trolox equivalents per kg fresh
      faeces. The TAC values on diets N (1.24 +/- 0.39 mmol/kg fresh faeces) and T
      (1.34 +/- 0.33 mmol/kg fresh faeces) were similar, but significantly higher on
      diet Q (2.32 +/- 0.61 mmol/kg fresh faeces). In contrast to expectations, faecal
      TAC increased with increasing faecal Fe, possibly as a result of the fact that
      the faecal Fe content was positively correlated to the proportion of concentrate
      feeds in the diet, which also contain antioxidants, such as vitamin E, in
      addition to Fe. Increased antioxidant status caused by the use of tannin
      substances could have a beneficial effect on animal health, but if tannins should
      be incorporated in designed diets, other tannin sources, such as grape pomace
      should be tested.

PMID- 16901278
TI  - Clinical, pathological and toxicological findings of a iatrogenic selenium
      toxicosis case in feeder pigs.
AB  - Histopathological and toxicological analyses confirmed a clinical diagnosis of
      selenium (Se) intoxication in pigs from a farm in Spain. After an initial episode
      of diarrhoea, animals presented both dermatological and neurological signs; the
      most obvious sign was a marked hind limb paresis. Cutaneous lesions consisted on
      diffuse alopecia, multifocal skin necrosis and coronary band necrosis of the
      hooves. Central nervous system lesions involved the cervical and lumbar
      intumescences of the spinal cord and consisted of a severe, bilateral symmetrical
      poliomyelomalacia of the ventral horns; pons and medulla oblongata also presented
      lesions of polioencephalomalacia. Analyses of feed and sera from clinically
      affected pigs revealed a marked increase in Se concentration. Clinical
      investigations indicated that a failure in Se dosage in feed was the cause of the
      toxicosis.

PMID- 16901279
TI  - Viral kinetics in the treatment of chronic hepatitis C.
AB  - Hepatitis C virus (HCV) is a major cause of chronic hepatitis and hepatic
      fibrosis, and chronic infection can frequently progress to cirrhosis, end-stage
      liver disease and hepatocellular carcinoma. Treatment with pegylated interferons
      (INFs) plus ribavirin has been shown to be more effective than pegylated INFs
      alone or standard INFs with or without ribavirin. The early response of HCV to
      treatment with peg-INF has been used to predict treatment outcomes in infected
      patients, emphasizing the importance of viral kinetics and genotyping in their
      treatment. Mathematic modelling of viral dynamics has shown the importance of
      optimal doses of drug, with early virologic response at week 12 predictive of
      sustained virologic response. Maintaining INF concentration above a
      therapeutically effective level is necessary to prevent viral rebound and
      subsequent treatment failure. Once-weekly dosing with peg-INF-alpha2a, which has
      a longer half-life than other forms of INF, plus daily dosing with ribavirin, has
      been shown to be effective in reducing viral load.

PMID- 16901280
TI  - Cytotoxic CD4 T cells in viral hepatitis.
AB  - CD4+ T cells are thought to contribute to antiviral immune responses by secretion
      of cytokines thereby providing help to CD8+ T and B cells. However, perforin
      positive cytotoxic CD4+ T cells have been described in human immunodeficiency
      virus-positive patients suggesting a role not only of CD8+ but also of CD4+ T
      cells for killing virus-infected cells. We investigated 76 patients with viral
      hepatitis [15 hepatitis B virus (HBV), 22 HBV/hepatitis D virus and 17 hepatitis
      C virus (HCV)] for cytotoxic CD4+ T cells. The frequency of perforin-positive
      CD4+ T cells in viral hepatitis was highly variable ranging from < 1% to more
      than 25%. Perforin-positive CD4+ T cells displayed the phenotype of terminally
      differentiated effector cells (CD28-, CD27-). The highest frequencies of CD4+
      cytotoxic T lymphocytes (CTLs) were found in patients with delta hepatitis (P =
      0.04 vs HBV and HCV patients), and the presence of CD4+ CTLs was associated with
      elevated aspartate aminotransferase levels (P = 0.01) and decreased platelet
      counts (P = 0.03). Perforin-positive CD4+ T cells decreased in two individuals
      during spontaneous clearance of acute hepatitis C. Significant associations were
      found between the frequency of perforin-expressing CD4+ cells and age (P = 0.04),
      perforin-positive CD8+ cells (P < 0.001) and perforin-positive CD4-/CD8- lymphoid
      cells (P = 0.002). Differentiated CD27- effector CD4+ CTLs can be detected in
      patients with viral hepatitis. In particular in patients with more advanced liver
      disease, the accumulation of perforin-positive T cells with age could be one
      correlate for the more severe course of viral hepatitis in elderly individuals.

PMID- 16901281
TI  - Identification of T-cell epitopes associated with immunity within the surface
      protein of duck hepatitis B virus.
AB  - Duck hepatitis is a convenient model of hepatitis B virus (HBV) infection, but
      the lack of immunological reagents hampers investigation of pathogenesis and
      vaccine development. The aim of this study was to define T-cell epitopes in the
      surface peptide recognized by vaccinated immune birds. Blastogenesis assays were
      used to test the proliferative response of spleen mononuclear cells to synthetic
      peptides spanning the pre-S/S region in 22 naive and 13 immunized and challenged
      immune ducks. Roughly > or = 50% of the immune ducks responded to five
      immunodominant peptides eliciting a statistically greater proliferative response
      than in naive birds. Fewer ducks responded to an additional six peptides. No
      statistically significant difference could be shown for the response to 11
      peptides between the immune ducks and the naive ducks. There was no clustering of
      the immunodominant peptides which were located throughout the surface antigen at
      sites of major swings in hydrophobicity. A number of peptides which induce
      lymphoblastogenesis in vaccinated immune ducks have been identified. Their role
      in spontaneous recovery from duck hepatitis B infection merits investigation.

PMID- 16901282
TI  - Identification of novel defective HCV clones in liver transplant recipients with
      recurrent HCV infection.
AB  - Patients with recurrent hepatitis C after liver transplantation usually have a
      high viral load and are generally resistant to interferon (IFN)-alpha2b plus
      ribavirin (RBV) therapy. However, it remains unclear whether pretreatment viral
      titre determines the effectiveness of combination therapy, especially in patients
      with a high viral load. The aim of this study was to identify the viral factors
      associated with a sustained virological response (SVR) to antiviral therapy in
      patients with recurrent hepatitis C after living-donor liver transplantation.
      Twenty-three patients with recurrent hepatitis C received combination therapy of
      IFN-alpha2b plus RBV. SVR was achieved in 7 of the 23 patients (30.4%).
      Predictive factors for SVR included a 2 log10 decline in Hepatitis C virus (HCV)
      RNA at 2 weeks after the start of therapy and disappearance of HCV RNA at 4 or 24
      weeks after the start of therapy. As the pretreatment high viral load showed no
      association with SVR, we asked whether other viral factor was associated with the
      response to the combination therapy in transplant recipients. We found the
      several novel defective HCV clones in 4 of 12 recipients' sera. All defective HCV
      clones had deletions in the envelope region. Interestingly, no patients with
      defective clones showed a prompt decrease in HCV RNA after the start of IFN
      alpha2b plus RBV therapy. Thus, early decline in serum HCV RNA after treatment
      was closely associated with SVR. The circulating defective HCV clones are present
      and might be associated with the response to the combination therapy in patients
      with recurrent hepatitis after liver transplantation.

PMID- 16901283
TI  - Absence of HCV viral recombination following superinfection.
AB  - We sought evidence of viral recombination in five recently hepatitis C virus
      (HCV) infected young injection drug users who became superinfected with a
      distinguishable strain of HCV. The entire open reading frame of plasma HCV
      genomes was reverse transcribed, polymerase chain reaction amplified in two
      fragments, and directly sequenced. In two cases of same subtype (1a > 1a)
      superinfections the initial and later strains were both sequenced and compared
      for evidence of recombination. In three cases of superinfection with strains of
      different genotype/subtype (3a > 1a, 1a > 3a, 1b > 1a), the later time point HCV
      genomes were sequenced and compared with representative genomes of the initial
      genotype/subtype. No evidence of intra- or inter-genotype/subtype recombination
      was detected using six different programs for detecting recombination. We
      conclude that the generation of viable recombinant HCV genomes able to dominate
      in the viral quasispecies is a rare event.

PMID- 16901284
TI  - Plasma ribavirin concentrations during treatment of recurrent hepatitis C with
      peginterferon alpha-2b and ribavirin combination after liver transplantation.
AB  - After liver transplantation (LT) for hepatitis C virus (HCV)-related cirrhosis,
      recurrence of HCV infection is universal. The efficacy of antiviral therapy in
      this indication is usually reduced because of its poor tolerability. We present
      herein the results of plasma measurement of ribavirin levels in transplanted
      patients when using increasing dosage of ribavirin, in comparison with a control
      cohort of nontransplanted patients. Seventeen control patients (nine women and
      eight men, median age 51.5 years) were compared with 12 liver transplant patients
      (2 women and 10 men, median age 55 years). In 76% of patients, HCV infection was
      genotype 1. All patients were treated by a combination of ribavirin and pegylated
      interferon alpha-2b. A total of 54 blood samples were taken (1.8 per patient) for
      ribavirin level measurement. A virological response was obtained in 8/17 patients
      in the control group and in 6/12 LT patients. Ribavirin dose was lower in the LT
      group (8.79 vs 12.98 mg/kg/day), but plasma levels were the same in both groups
      (2.23 vs 2.43 mg/L for LT and non-LT groups, respectively). This was probably
      related to impaired renal function in the LT group (serum creatinine: 112.6 vs
      73.6 micromol/L). No discontinuation of ribavirin therapy was observed and
      haemoglobin level was the same in both groups (109.5 g/L in LT patients vs 119.5
      g/L in the control group). These results strongly support the interest in plasma
      measurement of ribavirin concentration during antiviral therapy in LT patients.
      Ribavirin dosage might be adapted without compromising its efficacy.

PMID- 16901285
TI  - Sensitivity to antiviral therapy may change after liver transplantation in
      patients with chronic hepatitis C virus infection.
AB  - In hepatitis C virus (HCV)-infected patients, it is generally assumed that the
      pattern of response to antiviral therapy remains unaltered after liver
      transplantation (LT). However, changes in the circulating HCV quasispecies and in
      the gene expression profiles of the graft might influence response to treatment
      after LT. We evaluated 22 HCV-infected patients who received antiviral treatment
      while awaiting LT and in whom HCV infection recurred. Eleven of these patients
      underwent a new antiviral treatment course. Our study analyses the early
      virological response to both treatment courses to assess the influence of the
      changes in HCV on the response to therapy. Patients were considered early
      virological responders (EVR) if viral load declined > or = 2 log10 during the
      first 12 weeks of therapy. The remaining individuals were considered
      nonresponders (NR). HCV sequences from hypervariable region 1 and nonstructural
      5A (NS5A) region before both treatment regimens were compared. Of 11 patients, 8
      (73%) showed identical early response to both courses of therapy (group A: five
      EVR-EVR, three NR-NR). Interestingly, the response changed in three patients
      (27%) (group B): two NR became EVR after transplantation, whereas one EVR became
      NR. Fixation of mutations within the NS5A occurred preferentially in group B
      (100%) compared with group A (37%)(P = 0.12). However, the number of fixed
      mutations was not significantly different between groups, suggesting that the
      changes in sensitivity to therapy after LT are not exclusively dependent on
      variations in HCV strains. In conclusion, in HCV-infected patients undergoing LT,
      the pattern of response to antiviral treatment may change after transplantation,
      and this possibility needs to be incorporated in clinical practice.

PMID- 16901286
TI  - The results of a randomized trial looking at 24 weeks vs 48 weeks of treatment
      with peginterferon alpha-2a (40 kDa) and ribavirin combination therapy in
      patients with chronic hepatitis C genotype 1.
AB  - Peginterferon-alpha plus ribavirin is the most effective therapy for chronic
      hepatitis C. This study was designed to evaluate the effect of peginterferon
      alpha-2a (40 kDa) plus ribavirin on sustained virological response (SVR) when
      administered for 24 vs 48 weeks in genotype 1 naive patients. One hundred and
      seventeen patients were enrolled in this controlled trial. Genotype 1 patients
      were randomized to 24 weeks treatment vs 48 weeks treatment. Genotype non-1
      patients received 24 weeks treatment as an observational group. Outcomes were SVR
      (defined by hepatitis C virus-RNA-negative at week 24 of follow-up) and
      tolerability across the study period. The end-of-treatment response was 59% for
      genotype 1 (24 weeks treatment), 80% for genotype 1 (48 weeks treatment) and 92%
      for genotype non-1 (24 weeks treatment). The end-of-follow-up response was 19%
      (95% confidence interval (CI): 7.2-36.4) (genotype 1, 24 weeks) and 48% (95% CI:
      30.2-66.9; P = 0.0175) (genotype 1, 48 weeks). Among genotype non-1, SVR was 76%
      (95% CI: 62.3-86.5). There were no unexpected adverse events. Almost half of the
      genotype 1 patients achieved an SVR after 48 weeks treatment with peginterferon
      alpha-2a (40 kDa) and low-dose ribavirin and confirmed that they should be
      treated for 48 weeks. Safety profile was acceptable.

PMID- 16901287
TI  - Evidence for a substantial role of sharing of injecting paraphernalia other than
      syringes/needles to the spread of hepatitis C among injecting drug users.
AB  - In industrialized countries, transmission of hepatitis C occurs primarily through
      injecting drug use. Transmission of hepatitis C in injecting drug users is mainly
      associated with the sharing of contaminated syringes/needles, although evidence
      for risk of hepatitis C infection through sharing of other injecting
      paraphernalia is increasing. In this paper, the independent effects of sharing
      paraphernalia other than syringes/needles have been estimated. The prevalence and
      force of infection were modelled using three serological data sets from drug
      users in three centres in Belgium as a function of the sharing behaviour. It was
      found that sharing of materials other than syringes/needles indeed seemed to
      contribute substantially to the spread of hepatitis C among injecting drug users.

PMID- 16901289
TI  - The ComFor: an instrument for the indication of augmentative communication in
      people with autism and intellectual disability.
AB  - BACKGROUND: The ComFor (Forerunners in Communication) is an instrument to explore
      underlying competence for augmentative communication. More specifically, it
      measures perception and sense-making of non-transient forms of communication at
      the levels of presentation and representation. The target group consists
      primarily of individuals with autism and intellectual disability (ID) without or
      with only limited verbal communication. The ComFor is suitable for children and
      adults with a developmental level between 12 and 60 months. This paper describes
      the theoretical framework and structure of the ComFor, the results of a study on
      its psychometric properties and its clinical uses. METHOD: The ComFor was tested
      on a sample of 623 children and adults from the Netherlands and Flanders: a group
      with autism and ID (n = 310); a group with ID without autism (n = 174); and a
      control group of typically developing children (n = 139). RESULTS: The data
      generally support the reliability and validity of the ComFor. Internal
      consistency, inter-rater and test-retest reliability were found to be good.
      Construct validity (internal structure, convergent and divergent patterns) was
      established in different ways. The criterion-related validity has yet to be
      established, as predictive data are not available at the moment. CONCLUSION:
      Taken together, the results indicate that the ComFor is a promising instrument to
      explore underlying competence for augmentative communication. Areas for future
      research are outlined and the clinical relevance is discussed.

PMID- 16901290
TI  - An investigation into food preferences and the neural basis of food-related
      incentive motivation in Prader-Willi syndrome.
AB  - BACKGROUND: Research into the excessive eating behaviour associated with Prader
      Willi syndrome (PWS) to date has focused on homeostatic and behavioural
      investigations. The aim of this study was to examine the role of the reward
      system in such eating behaviour, in terms of both the pattern of food preferences
      and the neural substrates of incentive in the amygdala and orbitofrontal cortex
      (OFC). METHOD: Participants with PWS (n = 18) were given a food preference
      interview to examine food preferences and to inform the food-related incentive
      task to be conducted during the neuroimaging. Thirteen individuals with PWS took
      part in the positron emission tomography (PET) study, the design of which was
      based on a previous study of non-obese, non-PWS controls. For the task,
      participants were asked to consider photographs of food and to choose the food
      they would most like to eat in two conditions, one of high and one of low
      incentive foods, tailored to each participant's preferences. For comparison of
      the food preference data, 12 non-PWS individuals were given one part of the
      interview. RESULTS: Individuals with PWS expressed relative liking of different
      foods and showed preferences that were consistent over time, particularly for
      sweet foods. The participants with PWS did give the foods in the high incentive
      condition a significantly higher incentive value than the foods in the low
      incentive condition. However, activation of the amygdala and medial OFC was not
      associated with the prospect of highly valued foods as predicted in those with
      PWS. CONCLUSIONS: It would appear that incentive motivation alone plays a less
      powerful role in individuals with PWS than in those without the syndrome. This is
      likely to be due to the overriding intrinsic drive to eat because of a lack of
      satiety in those with PWS, and the impact of this on activity in the incentive
      processing regions of the brain. Activity in such reward areas may not then
      function to guide behaviour selectively towards the consumption of high
      preference foods.

PMID- 16901291
TI  - The acquisition of stimulus equivalence in individuals with fragile X syndrome.
AB  - BACKGROUND: Few studies have employed stimulus equivalence procedures to teach
      individuals with intellectual disabilities (IDs) new skills. To date, no studies
      of stimulus equivalence have been conducted in individuals with fragile X
      syndrome (FXS), the most common known cause of inherited ID. METHOD: Five
      adolescents with FXS were taught basic math and geography skills by using a
      computerized stimulus equivalence training programme administered over 2 days in
      2-h sessions. RESULTS: Four of the five participants learned the math relations,
      with one participant demonstrating stimulus equivalence at post-test. Three of
      the five participants learned the geography relations, with all three of these
      participants demonstrating stimulus equivalence at post-test. CONCLUSIONS: These
      data indicate that computerized stimulus equivalence procedures, conducted in
      time-limited sessions, may help individuals with FXS learn new skills. Hypotheses
      concerning the failure of some participants to learn the training relations and
      to demonstrate stimulus equivalence at post-test are discussed.

PMID- 16901292
TI  - Prevalence and types of aggressive behaviour among adults with intellectual
      disabilities.
AB  - BACKGROUND: Aggressive behaviours represent major obstacles to the integration
      into society of individuals with intellectual disability (ID) and pose
      significant management issues for carers. METHODS: The present study assessed the
      prevalence and severity of five types of aggressive behaviours in 3165 adult men
      and women with ID receiving services from three rehabilitation agencies in Quebec
      by surveying their carers using the Modified Overt Aggressive Scale. RESULTS: The
      12-month prevalence of aggressive behaviour was 51.8%: 24% property damage, 37.6%
      verbal, 24.4% self-oriented and 24.4% physical aggression, and 9.8% sexually
      aggressive behaviour, most of which being mild in severity. Only 4.9% of
      individuals displayed aggressive behaviour leading to injury of the victim. Few
      gender differences were observed. CONCLUSIONS: The capacity to document and
      assess the types as well as the severity of aggressive behaviour is thus
      critical, not only to better understand the correlates of various types of
      behaviours but also to orient intervention programmes whether they be prevention,
      assessment, monitoring or management of aggressive behaviour.

PMID- 16901293
TI  - Cognitive performance in Rett syndrome girls: a pilot study using eyetracking
      technology.
AB  - BACKGROUND: Rett syndrome (RS) is a pervasive developmental disorder with
      cognitive and neuromotor impairments (including loss of handiness and loss of
      communicative skills). OBJECTIVE: To verify whether girls with RS use their gaze
      intentionally, by observing their performance in three cognitive tasks: (1)
      verbal instruction condition (look at picture X), (2) recognition and matching of
      pictures (look at the one that is the same), and (3) categorization of pictures
      (look at the one that is similar). METHOD: Seven girls diagnosed with RS
      according to DSM-IV criteria were studied. Eyegaze technology was used to record
      the girls' eye movements' responses to visual stimulation. RESULTS: The
      comparison of fixation time on the alternatives revealed a higher percentage
      (62.4%) of correct alternatives (chi(2) = 76.31; P = 0.000). Of the seven
      children assessed, only one did not present predominance of fixations on the
      correct alternatives in any one of the tasks. One did well in all tasks. Six
      responded correctly to all verbal instructions. CONCLUSION: The rate of correct
      answers suggests that there is measurable and intentional gaze in RS girls and it
      can be used as a path to explore their cognitive performance.

PMID- 16901294
TI  - Improving the health of people with intellectual disabilities: outcomes of a
      health screening programme after 1 year.
AB  - BACKGROUND: People with intellectual disabilities (IDs) have a higher level of
      health needs, a higher level of which is unmet, compared with the general
      population. Health screening can detect unmet health needs, but it is unknown
      whether it effects beneficial health outcomes in the longer term. People with IDs
      are reliant on health management by proxy and there are many potential access
      barriers that may prevent health needs identified at screening from subsequently
      being met. This study aims to determine whether health gains can be detected 1
      year after a health screening programme specific to the needs of adults with IDs.
      METHODS: A total of 50 participants offered the health screen intervention were
      individually matched for gender, age and level of IDs with 50 control
      participants who received standard treatment only. Outcome measures after 1 year
      were semi-structured review of medical case notes, and semi-structured assessment
      with the people with IDs and their carer. RESULTS: During the 1-year period, the
      incidence of health need detection was more than twice as great for intervention,
      compared with control participants (mean number of new needs was 4.80 compared
      with 2.26; P < 0.001), and the level of met new health needs was greater (mean of
      3.56 compared with 2.26; P = 0.001). The level of met health promotion needs was
      also greater (P < 0.001), and more health monitoring needs were met for
      intervention compared with control participants (P = 0.039). CONCLUSIONS: This is
      the first study to demonstrate sustained benefits in health outcomes from a
      clinical intervention for adults with IDs compared with standard treatment alone.
      Its routine implementation is feasible, and would reduce health inequalities.

PMID- 16901295
TI  - Decision-making of Chinese caregivers for adult out-of-home placement.
AB  - BACKGROUND: In the light of the existence of lengthy waiting lists for out-of
      home placements, this study examines the factors affecting the decision to apply
      or not to apply for this facility in a city traditionally characterized by a
      cultural and policy emphasis on family responsibility and by relatively low
      levels of welfare commitment to residential services. METHOD: A sample of 321
      people responsible for providing care for adults with moderate to severe
      intellectual disability (ID) from 22 service units of seven non-governmental
      organizations in Hong Kong was surveyed by means of a structured questionnaire.
      RESULTS: The non-application group reported better emotional ties with the people
      with ID and greater confidence in their caregiving skills, but also tended to be
      caring for more challenging people with poorer health and higher or more frequent
      levels of self-harm behaviour than the application group who exhibited higher
      levels of worry and fear. Discriminant analysis successfully predicted 80% of non
      application cases, while logistic regression revealed that decline in perceived
      competence to care, absence of other health problems and at least one parent of
      the client having long-term illness were better predictors of the decision to
      apply than handicap-specific characteristics of the people with ID themselves.
      CONCLUSION: The implications of this finding are discussed, and consideration
      given to the possibility of developing policies designed to strengthen and
      treasure family values while not detracting from the importance of providing
      proper community support.

PMID- 16901296
TI  - The cognitive and behavioural phenotype of Roifman syndrome.
AB  - BACKGROUND: Roifman syndrome (OMIM 300258) is a multi-system disorder with a
      physical phenotype that includes Beta-cell immunodeficiency, intra-uterine and
      postnatal growth retardation, spondyloepiphyseal dysplasia, retinal dystrophy and
      characteristic facial dysmorphism. So far, six cases, all boys, have been
      reported in the literature. Roifman postulated that the syndrome may be due to a
      mutation in an X-linked gene or an autosomal gene giving rise to a sex-limited
      trait, but the definitive pathogenetic mechanism has still not been elucidated.
      Very little is known about the cognitive and behavioural phenotype of Roifman
      syndrome and no standardized measures of cognitive abilities have been reported.
      METHODS: We report the seventh case of a boy with Roifman syndrome and present
      the first systematic documentation of the cognitive and behavioural phenotype of
      an individual with the syndrome. RESULTS: In spite of having been reported as
      appearing intellectually 'able', formal evaluation showed very significant
      intellectual disability and neuropsychological impairment across cognitive
      domains. CONCLUSIONS: The findings suggest that Roifman syndrome may be an
      example of an X-linked mental retardation syndrome (XLMRS).

PMID- 16901299
TI  - Increased plasma levels of IL-6 in bacteremic periodontis patients after scaling.
AB  - Bacteremia frequently occurs after dental treatment. Periodontal inflammation may
      influence the incidence, magnitude and duration of bacteremia. The presence of
      circulating oral bacteria or bacterial components may induce cytokine synthesis
      in blood cells, which may contribute to the development or exacerbation of
      atherosclerosis. The present study tested the hypothesis that bacteremia
      occurring after scaling in periodontitis patients results in altered plasma
      levels of cytokines. Twenty periodontitis patients were subjected to scaling.
      Blood samples at baseline and at 0.5, 10 and 30 minutes postscaling were examined
      for bacteremia whereas baseline and eight-hour postscaling blood samples were
      examined for the levels of IL-1beta, TNF-alpha, IL-6, IL-8, IL-10 and IL-12p70.
      IL-6 levels were significantly increased eight hours after scaling, while IL-8
      was significantly decreased. No systematic changes occurred in the levels of IL
      1beta, TNF-alpha, IL-10 and IL-2p70. IL-6 levels may be increased while IL-8 may
      be decreased due to scaling, which may have implications for general health.

PMID- 16901300
TI  - Dermatological manifestations of Down's syndrome.
AB  - Down's syndrome (DS) is associated with rare dermatological disorders and
      increased frequency of some common dermatoses. Owing to advances in medical care
      and changes in attitude, the median age of death in this population has increased
      to 49 years, and the life expectancy of a 1-year-old person with DS today is more
      than 60 years and is likely to improve. With the increase in the number of
      individuals with DS in the population and an increased life span, dermatologists
      are more likely to encounter the wide spectrum of dermatological disorders that
      occurs in these patients. Furthermore, new reports of possible associations are
      frequent in the literature. The purpose of this article is to discuss the various
      dermatological conditions that affect DS individuals. A brief overview is given
      of the new information on genetics and the immunology of DS. We also discuss the
      molecular mechanisms of premature ageing, to which DS individuals are prone. We
      review the literature and discuss the known dermatological manifestations,
      concentrating on recent reports.

PMID- 16901301
TI  - Three years' experience with infliximab in recalcitrant psoriasis.
AB  - BACKGROUND: In this retrospective study, we report our experience with infliximab
      for recalcitrant psoriasis. METHODS: Twelve patients were treated between
      September 2001 and April 2005. Infliximab 5 mg/kg was given at 0, 2 and 6 weeks
      followed by 5 mg/kg at 8-week intervals. When two patients developed resistance
      to treatment, methotrexate was added at a dose of 5-7.5 mg weekly for all
      patients. Response to treatment was assessed with physician global assessment
      with a score of excellent, good, moderate, poor and failure. Ten patients had
      chronic plaque psoriasis, one had pustular palmoplantar psoriasis and one had
      acrodermatitis continua of Hallopeau. RESULTS: Nine patients, including the
      patient with acrodermatitis continua, showed an excellent response. Two patients
      initially showed good response but became resistant to treatment. One patient
      failed to respond, and treatment was discontinued. With time, six patients with
      excellent response and two with good response developed side-effects that
      necessitated stopping treatment. CONCLUSIONS: We have found infliximab to be very
      impressive, both in efficacy and speed of action, in severe psoriasis. Its use,
      however, is limited, as it requires hospital admission and by the need for
      concomitant methotrexate. Because of its powerful immunosuppressive action, the
      possibility of activating tuberculosis and inducing lymphoma remains a concern.

PMID- 16901302
TI  - Epidemiological study of severe cutaneous adverse drug reactions in a city
      district of China.
AB  - BACKGROUND: An epidemiological study of severe cutaneous adverse drug reactions
      (SCADRs) in China has not been reported. AIMS: To estimate the incidence of
      SCADRs in a city district of China. METHODS: A retrospective study was performed
      in Peking University Third Hospital, the only hospital in Haidian district,
      Beijing with a dermatology ward. The medical records of inpatients with SCADRs
      from January 1994 to December 2002 were studied. RESULTS: The prevalence rates
      for overall SCADRs, Stevens-Johnson syndrome (SJS), exfoliative dermatitis (ED),
      toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and
      systemic symptoms (DRESS) among hospitalized patients were 0.32, 0.15, 0.10, 0.04
      and 0.07 per thousand, respectively. The risk of SCADRs from systemic drugs among
      hospitalized patients was 0.03/1000 (0.02/1000 for SJS, and 0.01/1000 for ED and
      DRESS). The reported incidence of SCADRs in Haidian district was not less than
      1.8 per million person-years. The reported incidence of ED, SJS, TEN and DRESS in
      Haidian district was not less than 0.6, 0.8, 0.05 and 0.4 per million person
      years, respectively. The most common underlying disorders were infection, pain
      related diseases and epilepsy. Antibiotics were the most common offending drugs
      followed by anticonvulsants and traditional Chinese medicines (TCM). CONCLUSIONS:
      These results confirm the relatively low incidence of SCADRs in China.
      Antibiotics, anticonvulsants and TCM are the most common causative drugs.

PMID- 16901303
TI  - Management of basal cell carcinoma by surveyed dermatologists in Scotland.
AB  - BACKGROUND: The British Association of Dermatologists (BAD) has produced
      guidelines for management of basal cell carcinoma (BCC) in the UK. OBJECTIVES:
      Our primary objectives were to assess the management of BCCs in Scotland and to
      compare it with BAD guidelines. Our secondary objectives were to audit waiting
      times and referral patterns. METHODS: In phase I of the audit, dermatologists in
      14 centres across Scotland prospectively registered demographic and clinical data
      of all lesions suspected to be BCCs over a 6-week period between October and
      December 2000. In phase II, details of management of these lesions were evaluated
      by case note review. RESULTS: Of the 48 consultant dermatologists contacted, 42
      took part in the survey. There were 524 clinically suspected BCCs seen in 470
      patients; 164 lesions in 146 patients showed pathology other than BCC and were
      excluded from analysis, thus leaving 360 lesions available for analysis. There
      was wide variation in waiting times among Scottish dermatology centres. BCCs were
      equally distributed between the sexes, and lesions most commonly presented in
      those aged 71-80 years. A diagnostic biopsy was taken in 22% of lesions, and the
      rest were treated definitively after a clinical diagnosis of BCC, of which 90%
      were confirmed on histology. Nodulocystic lesions were the most common type of
      tumour, comprising 48% of lesions, and most BCCs were located on the head and
      neck region. Correlation of the histological type of BCC and treatment received
      showed that nodulocystic and morpheic BCCs were managed as recommended. There
      were more superficial BCCs treated with surgical excision than expected (22 of 34
      lesions). Four of 21 recurrent tumours and 9 of 81 tumours on high-risk areas of
      the face were managed with curettage and cautery or cryotherapy, rather than
      surgical excision. Of the 297 excised tumours, 25 (9%) were incompletely excised.
      All the high-risk tumours and incompletely excised tumours were offered follow-up
      in the dermatology clinics. CONCLUSIONS: In general, BCCs are managed according
      to BAD guidelines in Scotland, but waiting times vary considerably.

PMID- 16901304
TI  - Changes in the autoimmune blistering response: a clinical and immunopathological
      shift from pemphigus foliaceus to bullous pemphigoid.
AB  - We describe a 64-year-old Brazilian man who developed bullous pemphigoid (BP) 12
      years after pemphigus foliaceus (PF) was diagnosed. On his first presentation in
      1992, histological examination revealed intraepidermal blistering and
      acantholysis at the granular layer, direct immunofluorescence (DIF) demonstrated
      intercellular deposits of C3 in the epidermis, and indirect immunofluorescence
      showed the presence of IgG antibodies against the intercellular spaces. In 2004,
      laboratory findings revealed a subepidermal blister with neutrophils and
      eosinophils (by histology), DIF demonstrated deposition of IgG and C3 along the
      basement membrane zone, salt-split skin showed IgG deposition in the epidermal
      side of the blister, and immunoblotting showed reactivity against BP180. The
      occurrence of two autoimmune blistering conditions in the same patient is a rare
      event, and may suggest an intermolecular epitope-spreading phenomenon.

PMID- 16901306
TI  - Late-onset erythropoietic protoporphyria in association with haematological
      malignancy.

PMID- 16901305
TI  - Malignant melanoma arising from a congenital pigmented naevus in a patient with
      sarcoidosis: cause or coincidence?
AB  - A case is described of a 40-year-old man who developed sarcoidosis and at the
      same time malignant change in a congenital pigmented naevus of his foot. It is
      proposed that the sarcoidosis may have acted as a predisposing cause of the
      melanoma in this case. The difficulties of diagnosis and management of patients
      with coexistent malignant melanoma and sarcoidosis are discussed.

PMID- 16901307
TI  - Appropriateness of prescribing for childhood eczema: evidence from a community
      based study.
AB  - Data on dispensed prescriptions of topical corticosteroids and emollients were
      analysed in a population of 25 484 children aged<or=6 years in Tayside, Scotland.
      Over a 17-month period, 5818 (22.8%) children were prescribed a topical
      corticosteroid; half of this group, (2946; 50.6%) were not prescribed any
      emollient. In the group of children prescribed topical corticosteroids, 3505/5818
      (60.2%) received combined preparations of topical corticosteroids with
      antimicrobials over this time period, and potent or very potent preparations were
      prescribed for 923/5818 (15.9%).

PMID- 16901308
TI  - Penile colloid degeneration.
AB  - Colloid degeneration is a rare but well-recognized entity, usually occurring on
      chronically sun-exposed skin. We report a case occurring on penile skin with no
      history of such exposure.

PMID- 16901310
TI  - Genomic imprinting and dermatological disease.
AB  - Imprinting is the process whereby genetic alleles responsible for a phenotype are
      derived from one parent only. It is an epigenetic phenomenon resulting from DNA
      methylation or modification of protruding histones. When imprinted genes are
      disrupted, syndromes with characteristic patterns of inheritance and multisystem
      phenotype occur. Those detailed in this article have some quite characteristic
      cutaneous features and patterns of inheritance. These diseases include Beckwith
      Wiedmann, Silver-Russell, Prader-Willi, McCune-Albright and Angelman syndromes,
      Albright's hereditary osteodystrophy, and progressive osseous heteroplasia. In
      the case of Von Hippel-Lindau syndrome, hypomelanosis of Ito and dermatopathia
      pigmentosa reticularis, imprinting may play a part in the inheritance. With
      neurofibromatosis type 1, a nonimprinted condition, the expression of the
      phenotype could be affected by interaction with imprinted gene loci. Imprinted
      genes could also play a part in the polygenetic inheritance of more common
      diseases also, as atopic eczema and psoriasis may have predominantly maternal and
      paternal modes of transmission, respectively.

PMID- 16901309
TI  - A case of a Japanese neonate with congenital ichthyosiform erythroderma diagnosed
      as Netherton syndrome.
AB  - We report a 6-day-old Japanese girl showing generalized erythroderma accompanied
      by yellowish, exfoliative scaling that was accentuated on the face and scalp.
      Histological analysis showed psoriasiform dermatitis with acanthotic epidermis
      and premature shedding of the stratum corneum. Measurement of trypsin-like
      hydrolytic activity in SC showed six-fold greater activity compared with age
      matched controls. DNA analysis revealed two mutations, 375delAT and 966insC, in
      exons 5 and 11, respectively, of the SPINK5 gene. Although at 4 weeks the child
      was still too young to display characteristic hair abnormalities or atopic
      diathesis, we diagnosed Netherton syndrome based on enzyme assay and DNA
      analysis.

PMID- 16901311
TI  - Atrichia with papular lesions resulting from a novel insertion mutation in the
      human hairless gene.
AB  - BACKGROUND: Congenital atrichia with papular lesions is a rare, recessively
      inherited condition of total alopecia, characterized clinically by complete and
      irreversible hair loss, which begins shortly after birth with the development of
      the papular lesions of keratin-filled cysts over an extensive area of the body.
      Mutations in the human hairless (HR) gene have been implicated in the
      pathogenesis of this disorder. OBJECTIVE: To search for a mutation in human HR in
      a family with congenital atrichia. METHODS: Linkage analysis was carried out
      using genotyping markers closely linked to congenital atrichia locus on
      chromosome 8p12. Subsequently, human HR was sequenced to identify a disease
      causing mutation. RESULTS: A novel 11 bp insertion mutation, G202
      (InsCTTCCCCCAGG), in exon 2 of the hairless gene was identified in a Pakistani
      consanguineous family affected by congenital atrichia. The insertion results in
      the expansion of 11 bp tandem repeat, which introduces a translational frameshift
      leading to downstream premature termination codon. CONCLUSIONS: This mutation is
      the first insertion mutation identified in the coding sequence of human HR. This
      extends our knowledge of mutations in HR that define the pathogenic basis of this
      disease.

PMID- 16901312
TI  - Toll-like receptor 2 Arg753Gln gene polymorphism in Turkish patients with
      Behcet's disease.
AB  - Having considered the impact of the function of TLR2 in the recognition of
      several microorganisms that are thought to have an association with Behcet's
      disease (BD), we aimed to determine a possible association between the TLR2
      Arg753Gln polymorphism and susceptibility to BD. We genotyped 83 patients with
      BD, 95 ethnically matched healthy controls, 12 patients with recurrent aphthous
      stomatitis (RAS) and 21 patients with rheumatoid arthritis (RA) by restriction
      fragment length polymorphism after PCR amplification of the genomic region
      encompassing the polymorphic site. Comparison of the TLR2 Arg753Gln A allele and
      A/G genotype frequencies did not show a significant difference between patients
      with BD and healthy controls (1.2% vs. 0.6%, and 2.1% vs. 1.1%, respectively).
      None of the patients from the RAS and RA groups had the A allele or A/G genotype.
      Our results indicate that the TLR2 Arg753Gln polymorphism does not play a role in
      the aetiopathogenesis of BD.

PMID- 16901313
TI  - Mutations in the ATP2C1 gene in Chinese patients with Hailey-Hailey disease.
AB  - Hailey-Hailey disease (HHD; MIM 16960) is a rare autosomal dominant hereditary
      disorder characterized by recurrent eruption of vesicles and bullae,
      predominantly involving the body folds. It is caused by heterozygous mutations in
      the ATP2C1 gene, encoding the human secretory pathway Ca2+/Mn2+-ATPase protein 1
      (hSPCA1). When we studied Chinese patients with HHD, we found two different
      heterozygous mutations, Q506X and G353V, the former previously reported in a
      Hungarian patient, and the latter being a novel mutation. In a 38-year-old
      patient from a four-generation pedigree with a 3-year history of severe recurrent
      blisters, we identified a C-->T transition at nucleotide 1696, c(1696C-->T), in
      exon 17 of ATP2C1, resulting in a nonsenes mutation, Gln506X, which resulted in a
      premature termination codon. In the second patient, who represented a occurrence
      of sporadic Hailey-Hailey disease, a G-->T transversion of nucleotide, c(G1238T),
      in exon 13 of ATP2C1 was detected, which resulted in a Gly353-->Val amino acid
      substitution (G353V). Our molecular findings further demonstrate that the
      mutational events in the human ATP2C1 gene encoding the hSPCA1 pump play an
      important role in the pathogenesis of HHD.

PMID- 16901315
TI  - The 'St. Tropez' sign; a new dermoscopic feature of seborrhoeic keratoses?

PMID- 16901314
TI  - Angiosarcoma of the scrotum after treatment of cancer of the rectum.

PMID- 16901316
TI  - Eosinophilic pustular folliculitis successfully treated with sequential therapy
      of interferon-gamma and ciclosporin.

PMID- 16901318
TI  - A case of nail psoriasis treated with topical calcitriol.

PMID- 16901317
TI  - Human orf complicated by mucous membrane pemphigoid.

PMID- 16901319
TI  - The British Association of Dermatologists isotretinoin questionnaire for
      patients: a useful clinical tool.

PMID- 16901320
TI  - Tufted angioma in site of healed herpes zoster: isotopic response.

PMID- 16901321
TI  - Linearly distributed atrophic patches: a rare cutaneous manifestation of complex
      regional pain syndrome.

PMID- 16901322
TI  - Regression of BCC following immunosuppression withdrawal in a renal transplant
      recipient.

PMID- 16901323
TI  - Cultured autologous keratinocyte grafting of chronic erosions in three patients
      with epidermolysis bullosa.

PMID- 16901324
TI  - Phenytoin-induced DRESS with cross-reactivity to carbamazepine in a 10-year-old
      Indian child.

PMID- 16901325
TI  - Fatal outcome of generalized morphoea with bronchiolitis obliterans organizing
      pneumonia.

PMID- 16901326
TI  - A rash on the back. Diagnosis: confluent and reticulated papillomatosis (CRP) of
      Gougerot and Carteaud.

PMID- 16901327
TI  - An oedematous lesion in the nasolabial fold. Diagnosis: phymatous lesion with
      underlying rosacea.

PMID- 16901328
TI  - A palmar injury that failed to heal. Diagnosis: basal cell carcinoma of the palm.

PMID- 16901329
TI  - Painful leg ulcers and a rash in a patient with polycythaemia rubra vera.
      Diagnosis: hydroxyurea-induced leg ulceration and dermatomyositis-like skin
      changes.

PMID- 16901330
TI  - Oral ulcers on the vestibular sulci. Diagnosis: oral Crohn's disease.

PMID- 16901331
TI  - Erythema multiforme presenting as chronic oral ulceration due to unrecognised
      herpes simplex virus infection.

PMID- 16901332
TI  - The many faces of secondary syphilis: a re-emergence of an old disease.
AB  - There has been a recent dramatic re-emergence of syphilis in the UK. This article
      describes the varied clinical manifestations of secondary syphilis and describes
      the diagnosis and current guidelines for treatment, especially in association
      with human immunodeficiency virus infection.

PMID- 16901335
TI  - Will availability of inhaled human insulin (Exubera) improve management of type 2
      diabetes? The design of the Real World trial.
AB  - BACKGROUND: Common deterrents to insulin therapy for both physicians and patients
      are the complexity and burden of daily injections. In January 2006, the first
      inhaled human insulin (INH, Exubera (insulinhuman [rDNA origin])InhalationPowder)
      was approved for use in adult patients with type 1 diabetes mellitus (T1DM) or
      type 2 diabetes mellitus (T2DM) in the United States and European Union. Results
      from the INH clinical trial program have shown comparable efficacy of INH to
      subcutaneous (s.c.) insulin and superior efficacy versus oral antidiabetic
      agents; thus providing effective glycemic control in adult patients with T2DM
      without the requirement for preprandial injections. However, because subjects in
      those trials were randomized to either INH or an alternative, the studies could
      not estimate the effect of INH on patient acceptance of insulin therapy.
      Therefore, traditional study designs cannot provide answers to important and
      practical questions regarding real world effectiveness, which is influenced by
      psychological and other access barriers. METHODS: To overcome these limitations,
      the Real World Trial was designed to estimate the effect of the availability of
      INH as a treatment option for glycemic control. A total of approximately 700
      patients from Canada, France, Germany, Italy, Spain, United Kingdom, and the
      United States with T2DM poorly controlled by oral agent therapy will be
      randomized to two different treatment settings. Patients and clinicians in both
      groups (A & B) may choose from all licensed therapies for diabetes including SC
      insulin delivered by pens; INH will be an additional treatment option only
      available in Group A. The Real World Trial (Protocol A2171018) has been
      registered with ClincalTrials.gov, registration id NCT00134147. RESULTS: The
      primary outcome for the trial will be the difference in mean glycosylated
      hemoglobin (HbA1c) at 6 months between groups. The design was based on a
      preceding feasibility study examining the theoretical effects of inhaled insulin
      availability on treatment choice in 779 patients. In that study, patients were
      three times more likely to choose insulin therapy when inhaled insulin was
      available. CONCLUSION: Innovations in study designs may provide an opportunity to
      reveal unbiased answers to important treatment questions that are more relevant
      to prescribers, funding agencies, and healthcare policymakers.

PMID- 16901337
TI  - The relationship between reproductive outcome measures in DDT exposed malaria
      vector control workers: a cross-sectional study.
AB  - BACKGROUND: The utility of blood reproductive endocrine biomarkers for assessing
      or estimating semen quality was explored. METHODS: A cross-sectional study of 47
      DDT exposed malaria vector control workers was performed. Tests included blood
      basal and post gonadotrophin releasing hormone (GnRH), luteinizing hormone (LH),
      follicle stimulating hormone (FSH), testosterone, sex hormone binding globulin
      (SHBG), estradiol (E2) and inhibin; a questionnaire (demographics and general
      medical history); a physical examination and semen analysis. Semen parameters
      were determined using either/or or both WHO or the strict Tygerberg criteria.
      Relationships between semen parameters and endocrine measures were adjusted for
      age, duration of abstinence before sampling, presence of physical abnormalities
      and fever in the last two months. All relationships between specific endocrine
      hormones were adjusted for age and basal SHBG. RESULTS: Multiple logistic
      regression showed a consistent positive relationship (prevalence odds ratio (POR)
      = 8.2, CI:1.4-49.2) between low basal inhibin (< 100 pg/ml) and low semen count
      (< 40 million) and density (< 20 million/ml); consistent positive, but weaker
      relationships (1 > POR < 2) between abnormally low semen count as well as density
      and baseline and post GnRH FSH; and positive relationships (POR = 37, CI:2-655)
      between the prevalence of high basal estradiol (> 50 pg/ml) and abnormal
      morphology (proportion < 5%) and low motility (proportion < 50%). Most of the
      expected physiological relationships between specific endocrines were
      significant. CONCLUSION: The study has demonstrated that low basal inhibin,
      elevated basal FSH and high basal E2 can serve as markers of impaired semen
      quality.

PMID- 16901336
TI  - Morphological correlates to cognitive dysfunction in schizophrenia as studied
      with Bayesian regression.
AB  - BACKGROUND: Relationships between cognitive deficits and brain morphological
      changes observed in schizophrenia are alternately explained by less gray matter
      in the brain cerebral cortex, by alterations in neural circuitry involving the
      basal ganglia, and by alteration in cerebellar structures and related neural
      circuitry. This work explored a model encompassing all of these possibilities to
      identify the strongest morphological relationships to cognitive skill in
      schizophrenia. METHODS: Seventy-one patients with schizophrenia and sixty-five
      healthy control subjects were characterized by neuropsychological tests covering
      six functional domains. Measures of sixteen brain morphological structures were
      taken using semi-automatic and fully manual tracing of MRI images, with the full
      set of measures completed on thirty of the patients and twenty controls. Group
      differences were calculated. A Bayesian decision-theoretic method identified
      those morphological features, which best explained neuropsychological test scores
      in the context of a multivariate response linear model with interactions.
      RESULTS: Patients performed significantly worse on all neuropsychological tests
      except some regarding executive function. The most prominent morphological
      observations were enlarged ventricles, reduced posterior superior vermis gray
      matter volumes, and increased putamen gray matter volumes in the patients. The
      Bayesian method associated putamen volumes with verbal learning, vigilance, and
      (to a lesser extent) executive function, while caudate volumes were associated
      with working memory. Vermis regions were associated with vigilance, executive
      function, and, less strongly, visuo-motor speed. Ventricular volume was strongly
      associated with visuo-motor speed, vocabulary, and executive function. Those
      neuropsychological tests, which were strongly associated to ventricular volume,
      showed only weak association to diagnosis, possibly because ventricular volume
      was regarded a proxy for diagnosis. Diagnosis was strongly associated with the
      other neuropsychological tests, implying that the morphological associations for
      these tasks reflected morphological effects and not merely group volumetric
      differences. Interaction effects were rarely associated, indicating that
      volumetric relationships to neuropsychological performance were similar for both
      patients and controls. CONCLUSION: The association of subcortical and cerebellar
      structures to verbal learning, vigilance, and working memory supports the
      importance of neural connectivity to these functions. The finding that a
      morphological indicator of diagnosis (ventricular volume) provided more
      explanatory power than diagnosis itself for visuo-motor speed, vocabulary, and
      executive function suggests that volumetric abnormalities in the disease are more
      important for cognition than non-morphological features.

PMID- 16901338
TI  - Identification of 491 proteins in the tear fluid proteome reveals a large number
      of proteases and protease inhibitors.
AB  - BACKGROUND: The tear film is a thin layer of fluid that covers the ocular surface
      and is involved in lubrication and protection of the eye. Little is known about
      the protein composition of tear fluid but its deregulation is associated with
      disease states, such as diabetic dry eyes. This makes this body fluid an
      interesting candidate for in-depth proteomic analysis. RESULTS: In this study, we
      employ state-of-the-art mass spectrometric identification, using both a hybrid
      linear ion trap-Fourier transform (LTQ-FT) and a linear ion trap-Orbitrap (LTQ
      Orbitrap) mass spectrometer, and high confidence identification by two
      consecutive stages of peptide fragmentation (MS/MS/MS or MS3), to characterize
      the protein content of the tear fluid. Low microliter amounts of tear fluid
      samples were either pre-fractionated with one-dimensional SDS-PAGE and digested
      in situ with trypsin, or digested in solution. Five times more proteins were
      detected after gel electrophoresis compared to in solution digestion (320 versus
      63 proteins). Ontology classification revealed that 64 of the identified proteins
      are proteases or protease inhibitors. Of these, only 24 have previously been
      described as components of the tear fluid. We also identified 18 anti-oxidant
      enzymes, which protect the eye from harmful consequences of its exposure to
      oxygen. Only two proteins with this activity have been previously described in
      the literature. CONCLUSION: Interplay between proteases and protease inhibitors,
      and between oxidative reactions, is an important feature of the ocular
      environment. Identification of a large set of proteins participating in these
      reactions may allow discovery of molecular markers of disease conditions of the
      eye.

PMID- 16901340
TI  - Assessing the construct validity of the Italian version of the EQ-5D: preliminary
      results from a cross-sectional study in North Italy.
AB  - BACKGROUND: Information on health related quality of life (HR-QOL) can be
      integrated with other classical health status indicators and be used to assist
      policy makers in resource allocation decisions. For this reason instruments such
      as the SF-12 and EQ-5D have been widely proposed as assessment tools to monitor
      changes in HR-QOL in general populations and very recently in general practice
      settings as well AIM: The primary goal of our study was to assess the construct
      validity of the Italian version of the EQ-5D in a general population of North
      Italy using socio-demographic factors and diagnostic sub-groups. Our secondary
      goal was to assess the concurrent validity of the EQ-5D and SF-12. METHODS: The
      SF-12, the EQ-5D plus an additional questionnaire on socio-demographic
      characteristics, clinical conditions and symptoms were completed by 1,622 adults,
      randomly selected from the Registry of the Health Authorities of the city of
      Bologna, Italy. The primary care physician of each subject was contacted to
      report on the subject's health status. RESULTS: Our findings indicate that the
      Italian version of the EQ-5D is well accepted by the general population (91%
      response rate), has good reliability (Cronbach's alpha 0.73), and shows evidence
      of construct validity. CONCLUSION: Our data provide a basis for further research
      to be conducted to assess the validity of the EQ-5D in Italy. In particular
      future studies should focus on assessing its ability to detect a clinically
      important change in health related quality of life over time (responsiveness).

PMID- 16901341
TI  - Investigation of geo-spatial hotspots for the occurrence of tuberculosis in
      Almora district, India, using GIS and spatial scan statistic.
AB  - BACKGROUND: The World Health Organization has declared tuberculosis a global
      emergency in 1993. It has been estimated that one third of the world population
      is infected with Mycobacterium tuberculosis, the causative agent of tuberculosis.
      The emergence of TB/HIV co-infection poses an additional challenge for the
      control of tuberculosis throughout the world. The World Health Organization is
      supporting many developing countries to eradicate tuberculosis. It is an agony
      that one fifth of the tuberculosis patients worldwide are in India. The
      eradication of tuberculosis is the greatest public health challenge for this
      developing country. The aim of the present population based study on
      Mycobacterium tuberculosis is to test a large set of tuberculosis cases for the
      presence of statistically significant geographical clusters. A spatial scan
      statistic is used to identify purely spatial and space-time clusters of
      tuberculosis. RESULTS: Significant (p < 0.05 for primary clusters and p < 0.1 for
      secondary clusters) high rate spatial and space-time clusters were identified in
      three areas of the district. CONCLUSION: There is sufficient evidence about the
      existence of statistically significant tuberculosis clusters in Almora district
      of Uttaranchal, India. The spatial scan statistics methodology used in this study
      has a potential use in surveillance of tuberculosis for detecting the true
      clusters of the disease.

PMID- 16901339
TI  - Random mutagenesis in Corynebacterium glutamicum ATCC 13032 using an IS6100-based
      transposon vector identified the last unknown gene in the histidine biosynthesis
      pathway.
AB  - BACKGROUND: Corynebacterium glutamicum, a Gram-positive bacterium of the class
      Actinobacteria, is an industrially relevant producer of amino acids. Several
      methods for the targeted genetic manipulation of this organism and rational
      strain improvement have been developed. An efficient transposon mutagenesis
      system for the completely sequenced type strain ATCC 13032 would significantly
      advance functional genome analysis in this bacterium. RESULTS: A comprehensive
      transposon mutant library comprising 10,080 independent clones was constructed by
      electrotransformation of the restriction-deficient derivative of strain ATCC
      13032, C. glutamicum RES167, with an IS6100-containing non-replicative plasmid.
      Transposon mutants had stable cointegrates between the transposon vector and the
      chromosome. Altogether 172 transposon integration sites have been determined by
      sequencing of the chromosomal inserts, revealing that each integration occurred
      at a different locus. Statistical target site analyses revealed an apparent
      absence of a target site preference. From the library, auxotrophic mutants were
      obtained with a frequency of 2.9%. By auxanography analyses nearly two thirds of
      the auxotrophs were further characterized, including mutants with single, double
      and alternative nutritional requirements. In most cases the nutritional
      requirement observed could be correlated to the annotation of the mutated gene
      involved in the biosynthesis of an amino acid, a nucleotide or a vitamin. One
      notable exception was a clone mutagenized by transposition into the gene cg0910,
      which exhibited an auxotrophy for histidine. The protein sequence deduced from
      cg0910 showed high sequence similarities to inositol-1(or 4)-monophosphatases (EC
      3.1.3.25). Subsequent genetic deletion of cg0910 delivered the same histidine
      auxotrophic phenotype. Genetic complementation of the mutants as well as
      supplementation by histidinol suggests that cg0910 encodes the hitherto unknown
      essential L-histidinol-phosphate phosphatase (EC 3.1.3.15) in C. glutamicum. The
      cg0910 gene, renamed hisN, and its encoded enzyme have putative orthologs in
      almost all Actinobacteria, including mycobacteria and streptomycetes. CONCLUSION:
      The absence of regional and sequence preferences of IS6100-transposition
      demonstrate that the established system is suitable for efficient genome-scale
      random mutagenesis in the sequenced type strain C.glutamicum ATCC 13032. The
      identification of the hisN gene encoding histidinol-phosphate phosphatase in C.
      glutamicum closed the last gap in histidine synthesis in the Actinobacteria. The
      system might be a valuable genetic tool also in other bacteria due to the broad
      host-spectrum of IS6100.

PMID- 16901342
TI  - AICAR inhibits adipocyte differentiation in 3T3L1 and restores metabolic
      alterations in diet-induced obesity mice model.
AB  - BACKGROUND: Obesity is one of the principal causative factors involved in the
      development of metabolic syndrome. AMP-activated protein kinase (AMPK) is an
      energy sensor that regulates cellular metabolism. The role of AMP-activated
      protein kinase in adipocyte differentiation is not completely understood,
      therefore, we examined the effect of 5-aminoimidazole-4-carboxamide-1-beta-D
      ribofuranoside (AICAR), a pharmacological activator of AMP-activated protein
      kinase (AMPK) on adipocyte differentiation in 3T3L1 cells and in a mouse Diet
      induced obesity (DIO) model. METHODS: To examine the effect of AICAR on adipocyte
      differentiation in 3T3L1 cells and in a mouse Diet induced obesity (DIO) model,
      3T3L1 cells were differentiated in the presence or absence of different
      concentration of AICAR and neutral lipid content and expression of various
      adipocyte-specific transcription factors were examined. In vivo study, treated
      and untreated mice with AICAR (0.1-0.5 mg/g body weight) were fed high-fat diet
      (60% kcal% fat) to induce DIO and several parameters were studied. RESULTS: AICAR
      blocked adipogenic conversion in 3T3L1 cells along with significant decrease in
      the neutral lipid content by downregulating several adipocyte-specific
      transcription factors including peroxisome proliferators-activated receptor gamma
      (PPARgamma), C/EBPalpha and ADD1/SREBP1, which are critical for adipogenesis in
      vitro. Moreover, intraperitoneal administration of AICAR (0.5 mg g/body weight)
      to mice fed with high-fat diet (60% kcal% fat) to induce DIO, significantly
      blocked the body weight gain and total content of epididymal fat in these mice
      over a period of 6 weeks. AICAR treatment also restored normal adipokine levels
      and resulted in significant improvement in glucose tolerance and insulin
      sensitivity. The reduction in adipose tissue content in AICAR treated DIO mice
      was due to reduction in lipid accumulation in the pre-existing adipocytes.
      However, no change was observed in the expression of PPARgamma, C/EBPalpha and
      ADD1/SREBP1 transcription factors in vivo though PGC1alpha expression was
      significantly induced. CONCLUSION: This study suggests that AICAR inhibits
      adipocyte differentiation via downregulation of expression of adipogenic factors
      in vitro and reduces adipose tissue content in DIO mice by activating expression
      of PGC1alpha without inhibiting adipocyte-specific transcription factors in DIO
      mice.

PMID- 16901343
TI  - Does architectural lighting contribute to breast cancer?
AB  - OBJECTIVES: There is a growing interest in the role that light plays on nocturnal
      melatonin production and, perhaps thereby, the incidence of breast cancer in
      modern societies. The direct causal relationships in this logical chain have not,
      however, been fully established and the weakest link is an inability to
      quantitatively specify architectural lighting as a stimulus for the circadian
      system. The purpose of the present paper is to draw attention to this weakness.
      DATA SOURCES AND EXTRACTION: We reviewed the literature on the relationship
      between melatonin, light at night, and cancer risk in humans and tumor growth in
      animals. More specifically, we focused on the impact of light on nocturnal
      melatonin suppression in humans and on the applicability of these data to women
      in real-life situations. Photometric measurement data from the lighted
      environment of women at work and at home is also reported. DATA SYNTHESIS: The
      literature review and measurement data demonstrate that more quantitative
      knowledge is needed about circadian light exposures actually experienced by women
      and girls in modern societies. CONCLUSION: Without such quantitative knowledge,
      limited insights can be gained about the causal relationship between melatonin
      and the etiology of breast cancer from epidemiological studies and from
      parametric studies using animal models.

PMID- 16901344
TI  - Immunohistochemical detection of hTERT in urothelial lesions: a potential adjunct
      to urine cytology.
AB  - BACKGROUND: Urine cytology has a critical role in evaluation for bladder
      carcinoma. Due to the low sensitivity of this technique, ancillary modalities
      such as the detection of markers of malignancy by immunochemistry are desirable.
      Promising factors in this context are components of the human telomerase enzyme
      complex. Telomerase repairs and extend telomeres, which when eroded beyond a
      critical limit trigger a senescence checkpoint. Accordingly, while absent in
      normal somatic cells, telomerase activity has been detected in the great majority
      of malignant tumor specimens tested, and so has potential value for the
      recognition of malignant cells in clinical specimens. METHODS: In this study, we
      investigated whether the immunohistochemical detection of the catalytic subunit
      of telomerase (hTERT) can aid cytology in the diagnosis of bladder lesions.
      Findings from the retrospective evaluation of over 100 cell blocks, including
      urine sediments from confirmed malignant and benign conditions, were compared
      with routine urine cytology data. RESULTS: The presence of hTERT protein was
      indicative of the transformation of urothelia to a malignant phenotype. Nucleolar
      hTERT was expressed in 27 (93%) of 29 samples obtained from patients with
      confirmed primary bladder cancer. Conversely, hTERT was detectable in only 3
      (0.8%) of 39 samples from benign conditions. The hTERT assay showed higher
      diagnostic sensitivity (84.8%) than published urine cytology data (approximately
      65%) for confirmed bladder carcinoma, however, the hTERT assay was less specific
      than cytology (65.2% vs. approximately 95% respectively). CONCLUSION: As a highly
      sensitive marker, immunohistochemical hTERT detection in urine sediments
      represents a reliable adjunct to cytology in the accurate diagnosis of urothelial
      neoplasms.

PMID- 16901345
TI  - Cytodiagnosis of multiple myeloma presenting as orbital involvement: a case
      report.
AB  - BACKGROUND: Plasma cell neoplasms represent autonomous proliferations of plasma
      cells and can manifest as diffuse myeloma with systemic involvement (plasma cell
      myeloma or multiple myeloma), monoclonal gammopathy of undetermined significance
      (MGUS), or as variants of plasma cell myeloma such as indolent myeloma,
      smoldering myeloma, osteosclerotic myeloma, plasma cell leukaemia and non
      secretory myeloma. Localized neoplastic proliferation of plasma cells presents as
      solitary plasmacytoma of bone or extramedullary plasmacytoma. Involvement of
      orbit can occur as a solitary plasmacytoma, or as part of systemic involvement in
      multiple myeloma, the clinical outcome being significantly worse in the latter
      setting. Orbital involvement in multiple myeloma is very rare with less than 50
      cases reported in the literature. Early cytological diagnosis of such lesions is
      vital for timely institution of appropriate therapy. As far as we are aware only
      six previous cases of cytological diagnosis of multiple myeloma involving the
      orbit are on record. CASE PRESENTATION: A 37 year old male presented with low
      grade fever showing evening rise, headache, diplopia and swelling in the right
      periorbital and temporal region. Imaging studies revealed destructive lesion of
      sphenoid, frontal bone and zygomatic arch with soft tissue component extending to
      infratemporal fossa and orbit. A fine needle aspirate from the temporal region
      swelling showed features of a plasmacytoma, and subsequent workup confirmed the
      presence of systemic disease. A final diagnosis of multiple myeloma with orbital
      involvement at presentation was made. CONCLUSION: Present case describes the
      extremely rare presentation of multiple myeloma with orbital involvement and
      highlights the utility of cytology in such lesions. Fine needle aspiration
      diagnosis of plasmacytoma at extramedullary sites offers an opportunity for non
      invasive verification of systemic involvement, and thus plays a major role in
      early diagnosis and management of these patients.

PMID- 16901346
TI  - Validating MOSPA questionnaire for measuring physical activity in Pakistani
      women.
AB  - BACKGROUND: Precise measurements of activity at a population level are important
      for monitoring trends and evaluating health promotion strategies. Few studies
      have assessed the measurement of physical activity in developing countries. The
      aim of this study was to validate the MOSPA (Monica Optional Study of Physical
      Activity) questionnaire which was developed for the WHO-Monitoring trends and
      determinants of cardiovasculr disease (MONICA) study sites. METHODS: The MOSPA
      questionnaire assesses energy expendtiture (EE) related to physical activity
      (employment, household work, transportation, and leisure time) over a one year
      period. This questionnaire has been described in the manuscript as the long term
      (LT) questionnaire. An adapted short term (ST) 5 day questionnaire was developed
      to assess convergent validity. Questionnaire data were compared with physical
      activity EE estimates from a Caltrac accelerometer and with body composition
      measures (height, weight and bioelectrical impedance) in 50 women from the Aga
      Khan University (AKU) hospital antenatal clinics, Pakistan. Other forms of EE
      i.e. resting EE and thermic effect of food were not assessd in this study.
      RESULTS: Subjects were aged 26 +/- 3.8 years and were 16.1 +/- 6.7 weeks
      pregnant. Their average weight was 58.8 +/- 10.7 Kg. The average EE/day assessed
      by the Caltrac accelerometer, was 224 kcal and by MOSPA LT questionnaire it was
      404 kcal. The questionnaires and Caltrac data were reasonably well correlated: r
      = 0.51 and r = 0.60 (P < 0.01) for LT and ST questionnaires respectively. Energy
      expenditure from questionnaire data was not correlated with body composition
      measures. CONCLUSION: The MOSPA questionnaire is useful in assessing physical
      activity levels in a sedentary population over a one year period.

PMID- 16901347
TI  - Pothead or pot smoker? A taxometric investigation of cannabis dependence.
AB  - BACKGROUND: Taxometric methods were used to discern the latent structure of
      cannabis dependence. Such methods help determine if a construct is categorical or
      dimensional. Taxometric analyses (MAXEIG and MAMBAC) were conducted on data from
      1,474 cannabis-using respondents to the 2001-2002 National Epidemiologic Survey
      on Alcohol and Related Conditions (NESARC). Respondents answered questions
      assessing DSM-IV criteria for cannabis dependence. RESULTS: Both taxometric
      methods provided support for a dimensional structure of cannabis dependence.
      CONCLUSION: Although the MAMBAC results were not entirely unequivocal, the
      majority of evidence favored a dimensional structure of cannabis dependence.

PMID- 16901348
TI  - Health-related quality of life in food hypersensitive schoolchildren and their
      families: parents' perceptions.
AB  - BACKGROUND: About 20% of schoolchildren and adolescents in Sweden suffer from
      perceived food hypersensitivity (e.g. allergy or intolerance). Our knowledge of
      how child food hypersensitivity affects parents HRQL and what aspects of the
      hypersensitivity condition relate to HRQL deterioration in the family is limited.
      Thus the aim of this study was to investigate the parent-reported HRQL in
      families with a schoolchild considered to be food hypersensitive. The allergy
      associated parameters we operated with were number of offending food items,
      adverse food reactions, additional hypersensitivity, allergic diseases and
      additional family members with food hypersensitivity. These parameters, along
      with age and gender were assessed in relation to child, parent and family HRQL.
      METHODS: In May 2004, a postal questionnaire was distributed to parents of 220
      schoolchildren with parent-reported food hypersensitivity (response rate 74%).
      Two questionnaires were used: CHQ-PF28 and a study-specific questionnaire
      including questions on allergy-associated parameters. In order to find factors
      that predict impact on HRQL, stepwise multiple linear regression analyses were
      carried out. RESULTS: An important predictor of low HRQL was allergic disease
      (i.e. asthma, eczema, rhino conjunctivitis) in addition to food hypersensitivity.
      The higher the number of allergic diseases, the lower the physical HRQL for the
      child, the lower the parental HRQL and the more disruption in family activities.
      Male gender predicted lower physical HRQL than female gender. If the child had
      sibling(s) with food hypersensitivity this predicted lower psychosocial HRQL for
      the child and lower parental HRQL. Food-induced gastro-intestinal symptoms
      predicted lower parental HRQL while food-induced breathing difficulties predicted
      higher psychosocial HRQL for the child and enhanced HRQL with regards to the
      family's ability to get along. CONCLUSION: The variance in the child's physical
      HRQL was to a considerable extent explained by the presence of allergic disease.
      However, food hypersensitivity by itself was associated with deterioration of
      child's psychosocial HRQL, regardless of additional allergic disease. The results
      suggest that it is rather the risk of food reactions and measures to avoid them
      that are associated with lower HRQL than the clinical reactivity induced by food
      intake. Therefore, food hypersensitivity must be considered to have a strong
      psychosocial impact.

PMID- 16901349
TI  - Combined determination of plasma MMP2, MMP9, and TIMP1 improves the non-invasive
      detection of transitional cell carcinoma of the bladder.
AB  - BACKGROUND: Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) play a
      major role in the maintenance of extracellular matrix homeostasis and are
      involved in the process of tumour invasion and metastasis in several malignant
      tumour entities. The goal of this study is to evaluate the diagnostic value of
      various circulating MMPs and TIMPs in blood plasma for a non-invasive detection
      of transitional cell carcinoma of the bladder (TCC). METHODS: In this study the
      concentrations of MMP1, MMP2, MMP3, MMP9, their inhibitors TIMP1, TIMP2, and the
      MMP1/TIMP1-complex (MTC1) were quantified in blood plasma with the sandwich
      enzyme-linked immunosorbent assay (ELISA). Blood plasma samples were investigated
      from 68 patients (non-metastasized, n = 57 and metastasized, n = 11) with TCC of
      the bladder and from 79 healthy controls. The mROC program was used to calculate
      the best two- and three- marker combinations. The diagnostic values for all
      single markers and the marker combinations were estimated both by the overall
      diagnostic performance index area under the ROC curve (AUC) and the sensitivity
      and specificity at cutoff limits with the highest diagnostic accuracy and at the
      90% and 95% limits of sensitivity and specificity, respectively. RESULTS: The
      median MMP2 concentration was elevated in blood plasma in all patient groups with
      TCC in comparison to the controls (p < 0.001). The concentrations of TIMP1,
      TIMP2, and MTC1 in plasma probes were significantly lower from patients with non
      metastasized TCC compared to the controls. MMP2 tested alone reached the highest
      sensitivity and specificity at 75%, respectively. The sensitivity and specificity
      increased when tested in combination with MMP9 and TIMP1 (97%, 94%,
      respectively). The combination of MMP9 and TIMP1 also showed an improved
      sensitivity (80%) and specificity (99%) than tested alone. CONCLUSION: MMP2 is a
      statistically significant marker in blood plasma for bladder cancer detection
      with an increased diagnostic value in combination with MMP9 and TIMP1. This study
      showed that the highest sensitivities and specificities are not obtained by
      testing each marker alone. As shown by the best two-marker combination, which
      includes MMP9 and TIMP1, the optimized combination does not always include the
      best single markers.

PMID- 16901350
TI  - Effect of left atrial compliance on pulmonary artery pressure: a case report.
AB  - BACKGROUND: Left ventricular diastolic dysfunction, with secondary atrial
      pressure elevation, is a well-known concept. On the contrary, effect of left
      atrial compliance on pulmonary pressure is rarely considered. CASE PRESENTATION:
      We report the echocardiographic case of a 9-year-old child who presented severe
      rheumatic mitral valve regurgitation with a giant left atrium, in contrast to a
      normal artery pulmonary pressure, testifying of the high left atrial compliance.
      CONCLUSION: Left atrial compliance is an important determinant of symptoms and
      pulmonary artery pressure in mitral valve disease.

PMID- 16901351
TI  - UniPep--a database for human N-linked glycosites: a resource for biomarker
      discovery.
AB  - There has been considerable recent interest in proteomic analyses of plasma for
      the purpose of discovering biomarkers. Profiling N-linked glycopeptides is a
      particularly promising method because the population of N-linked glycosites
      represents the proteomes of plasma, the cell surface, and secreted proteins at
      very low redundancy and provides a compelling link between the tissue and plasma
      proteomes. Here, we describe UniPep http://www.unipep.org--a database of human N
      linked glycosites--as a resource for biomarker discovery.

PMID- 16901352
TI  - Text mining of full-text journal articles combined with gene expression analysis
      reveals a relationship between sphingosine-1-phosphate and invasiveness of a
      glioblastoma cell line.
AB  - BACKGROUND: Sphingosine 1-phosphate (S1P), a lysophospholipid, is involved in
      various cellular processes such as migration, proliferation, and survival. To
      date, the impact of S1P on human glioblastoma is not fully understood.
      Particularly, the concerted role played by matrix metalloproteinases (MMP) and
      S1P in aggressive tumor behavior and angiogenesis remains to be elucidated.
      RESULTS: To gain new insights in the effect of S1P on angiogenesis and invasion
      of this type of malignant tumor, we used microarrays to investigate the gene
      expression in glioblastoma as a response to S1P administration in vitro. We
      compared the expression profiles for the same cell lines under the influence of
      epidermal growth factor (EGF), an important growth factor. We found a set of 72
      genes that are significantly differentially expressed as a unique response to
      S1P. Based on the result of mining full-text articles from 20 scientific journals
      in the field of cancer research published over a period of five years, we
      inferred gene-gene interaction networks for these 72 differentially expressed
      genes. Among the generated networks, we identified a particularly interesting
      one. It describes a cascading event, triggered by S1P, leading to the
      transactivation of MMP-9 via neuregulin-1 (NRG-1), vascular endothelial growth
      factor (VEGF), and the urokinase-type plasminogen activator (uPA). This
      interaction network has the potential to shed new light on our understanding of
      the role played by MMP-9 in invasive glioblastomas. CONCLUSION: Automated
      extraction of information from biological literature promises to play an
      increasingly important role in biological knowledge discovery. This is
      particularly true for high-throughput approaches, such as microarrays, and for
      combining and integrating data from different sources. Text mining may hold the
      key to unraveling previously unknown relationships between biological entities
      and could develop into an indispensable instrument in the process of formulating
      novel and potentially promising hypotheses.

PMID- 16901353
TI  - Genome comparison using Gene Ontology (GO) with statistical testing.
AB  - BACKGROUND: Automated comparison of complete sets of genes encoded in two genomes
      can provide insight on the genetic basis of differences in biological traits
      between species. Gene ontology (GO) is used as a common vocabulary to annotate
      genes for comparison. Current approaches calculate the fold of unweighted or
      weighted differences between two species at the high-level GO functional
      categories. However, to ensure the reliability of the differences detected, it is
      important to evaluate their statistical significance. It is also useful to search
      for differences at all levels of GO. RESULTS: We propose a statistical approach
      to find reliable differences between the complete sets of genes encoded in two
      genomes at all levels of GO. The genes are first assigned GO terms from BLAST
      searches against genes with known GO assignments, and for each GO term the
      abundance of genes in the two genomes is compared using a chi-squared test
      followed by false discovery rate (FDR) correction. We applied this method to find
      statistically significant differences between two cyanobacteria, Synechocystis
      sp. PCC6803 and Anabaena sp. PCC7120. We then studied how the set of identified
      differences vary when different BLAST cutoffs are used. We also studied how the
      results vary when only subsets of the genes were used in the comparison of human
      vs. mouse and that of Saccharomyces cerevisiae vs. Schizosaccharomyces pombe.
      CONCLUSION: There is a surprising lack of statistical approaches for comparing
      complete genomes at all levels of GO. With the rapid increase of the number of
      sequenced genomes, we hope that the approach we proposed and tested can make
      valuable contribution to comparative genomics.

PMID- 16901354
TI  - The course of pain drawings during a 10-week treatment period in patients with
      acute and sub-acute low back pain.
AB  - BACKGROUND: Pain drawings are widely used as an assessment of patients'
      subjective pain in low back pain patients being considered for surgery. Less work
      has been done on primary health care patients. Moreover, the possible correlation
      between pain drawing modalities and other pain assessment methods, such as pain
      score and functional variables needs to be described. Thus, the objectives were
      to describe the course of pain drawings during treatment in primary health care
      for low back pain patients. METHODS: 160 primary health care outpatients with
      acute or sub-acute low back pain were studied during 10 weeks of a stay active
      concept versus manual therapy in addition to the stay active concept. The
      patients filled out 3 pain drawings each, at baseline and after 5 and 10 weeks of
      treatment. In addition the patients also reported pain and functional variables
      during the 3 measurement periods. RESULTS: The proportion of areas marked, the
      mean number of areas marked (pain drawing score), mean number of modalities used
      (area score), and the proportion of patients with pain radiation all decreased
      during the 10-week treatment period. Most of the improvement occurred during the
      first half of the period. The seven different pain modalities in the pain drawing
      were correlated to pain and functional variables. In case of no radiation some
      modalities were associated with more pain and disability than others, a finding
      that grew stronger over time. For patients with pain radiation, the modality
      differences were smaller and inconsistent. CONCLUSION: Pain modalities are
      significantly correlated with pain and functional variables. There is a shift
      from painful modalities to less painful ones over time.

PMID- 16901355
TI  - Power spectrum density of EEGs of sleeping epilepsy-prone El mice and their non
      epileptic mother strain.
AB  - A power spectrum density (PSD) analysis was performed on electroencephalograms
      (EEG) of sleeping epileptic El mice and non-epileptic ddY mice. A respiratory
      peak at 3.13 Hz was detected in the EEGs of both categories. The PSD analysis
      revealed a peak at 8.59 Hz in the El mice, which was associated with interictal
      discharges. This peak may be helpful in diagnosing epilepsy.

PMID- 16901357
TI  - Systematic review of medium-term weight loss after bariatric operations.
AB  - BACKGROUND: Although bariatric surgery is known to be effective in the short
      term, the durability of that effect has not been convincingly demonstrated over
      the medium term (> 3 years) and the long term (> 10 years). The authors studied
      the durability of weight loss after bariatric surgery based on a systematic
      review of the published literature. METHODS: All reports published up to
      September, 2005 were included if they were full papers in refereed journals
      published in English, of outcomes after Roux-en-Y gastric bypass (RYGBP), and its
      hybrid procedures of banded bypass (Banded RYGBP) and longlimb bypass (LL-RYGBP),
      biliopancreatic diversion with or without duodenal switch (BPD+/-DS) or
      laparoscopic adjustable gastric banding (LAGB). All reports that had at least 100
      patients at commencement, and provided > or = 3 years of follow-up data were
      included. RESULTS: From a total of 1,703 reports extracted, 43 reports fulfilled
      the entry criteria (18 RYGBP; 18 LAGB; 7 BPD). Pooled data from all the bariatric
      operations showed effective and durable weight loss to 10 years. Mean %EWL for
      standard RYGBP was higher than for LAGB at years 1 and 2 (67 vs 42; 67 vs 53) but
      not different at 3, 4, 5, 6 or 7 years (62 vs 55; 58 vs 55; 58 vs 55; 53 vs 50;
      and 55 vs 51). There was 59 %EWL for LAGB at 8 years, and 52 %EWL for RYGBP at 10
      years. Both the BPD+/-DS and the Banded RYGBP appeared to show better weight loss
      than standard RYGBP and LAGB, but with statistically significant differences
      present at year 5 alone. The LL-RYGBP was not associated with improved %EWL.
      Important limitations include lack of data on loss to follow-up, failure to
      identify numbers of patients measured at each data point and lack of data beyond
      10 years. CONCLUSIONS: All current bariatric operations lead to major weight loss
      in the medium term. BPD and Banded RYGBP appear to be more effective than both
      RYGBP and LAGB which are equal in the medium term.

PMID- 16901358
TI  - Comparison of nutritional consequences of conventional therapy of obesity,
      adjustable gastric banding, and gastric bypass.
AB  - BACKGROUND: Roux-en-Y gastric bypass (RYGBP) is more efficient than adjustable
      gastric banding (AGB) in weight loss and relieving co-morbidities, but
      nutritional complications of each surgical procedure have been poorly evaluated.
      METHODS: A cross-sectional study was performed to compare nutritional parameters
      in 201 consecutive obese patients, who had been treated either by conventional
      behavioral and dietary therapy (CT, n=110) or by bariatric surgery, including 51
      AGB and 40 RYGBP. RESULTS: BMI was similar after AGB (36.6 +/- 5.3 kg/m2) and
      RYGBP (35.4 +/- 6.3 kg/m2), but patients in the RYGBP group had lost more weight
      and had less metabolic disturbances than those in the AGB group. On the other
      hand, the prevalence of nutritional deficits was significantly higher in the
      RYGBP group than in the 2 other groups (P<0.01), whereas the AGB group did not
      differ from CT. Particularly, the RYGBP group presented an unexpected high
      frequency of deficiencies in fat-soluble vitamins. Moreover, vitamin B12,
      hemoglobin, plasma prealbumin and creatinine concentrations were low in the RYGBP
      group. CONCLUSION: RYGBP is more efficient than AGB in correcting obesity, but
      this operation is associated with a higher frequency of nutritional deficits that
      should be carefully monitored.

PMID- 16901359
TI  - Fatal complications of bariatric surgery.
AB  - BACKGROUND: Bariatric surgery is an increasingly used method to treat morbid
      obesity. The mortality rate among patients undergoing bariatric operations is
      generally quoted as between 0.05-2.0%. Our focus was not on mortality rates but
      rather on the reasons patients die following the procedures. In New York City,
      deaths that are due to predictable complications of appropriate therapy are
      certified as therapeutic complications. METHODS: We retrospectively reviewed all
      deaths investigated by the Office of the Chief Medical Examiner in New York City
      between 1997 and 2005 in which bariatric surgery had been performed. We report
      the fatal complications, the interval between surgery and death, the type of
      procedure, and coexisting morbidities. RESULTS: Autopsies were performed on 95%
      of these fatalities. There were 97 deaths due to therapeutic complications of the
      operations. The interval between the initial surgery and death ranged from
      several hours to years. The most common complication was an anastomotic leak with
      subsequent infection. A high percentage of deaths occurred after discharge (40%)
      and/or >30 days after surgery (37%). There were 8 deaths from complications of
      bariatric surgery that occurred >1 year after surgery. CONCLUSIONS: Studies that
      report the mortality rate during hospitalization or within 30 days of surgery,
      underestimate the actual incidence. Bariatric surgery carries both short- and
      long-term risks.

PMID- 16901360
TI  - Impact of gastric banding on plasma adiponectin levels.
AB  - BACKGROUND: Several endocrine abnormalities are reported in obesity. In an
      earlier study, we found that the changes in BMI following laparoscopic adjustable
      gastric banding (LAGB) were associated with changes in hormone profiles such as
      insulin and proinsulin. In the current study, we explored the changes in plasma
      adiponectin levels in morbidly obese subjects who lost abundant weight following
      LAGB. METHODS: 23 adult morbidly obese patients (15 females), aged 21-56 years,
      were studied. Blood samples were collected before, and 6 and 14 months after
      LAGB. The plasma adiponectin levels were determined by commercial kit (B-Bridge
      International, Inc). Statistical analysis was based on one-way repeated measures
      ANOVA, followed by Student-Newman-Keuls post-hoc test. Regression model was used
      to look for predictors of adiponectin change after LAGB. RESULTS: Mean BMI before
      surgery was 46.04+/-4.44 kg/m2, and decreased significantly by 18% 6 months after
      surgery to 37.67+/-4.47 kg/m2. BMI further decreased by 32% 14 months after
      surgery to a mean of 31.30+/-4.65 kg/m2 (P=.000). The mean adiponectin level
      before surgery was 3997+/-1766 microg/ml, and increased significantly by 16% to
      4763+/-1776 microg/ml 6 months after surgery, and to 6336+/-3292 microg/ml (37%)
      14 months after surgery. Although BMI persistently decreased, while adiponectin
      persistently increased, BMI did not correlate with adiponectin. CONCLUSION: In
      morbidly obese patients who underwent LAGB, adiponectin levels persistently
      increased, probably due to the reduction of visceral fat mass. Adiponectin plasma
      increase was correlated with proinsulin levels prior to the surgery. The
      interaction between adiponectin, proinsulin and BMI change in morbid obesity
      merits further investigation.

PMID- 16901361
TI  - Laparoscopic adjustable gastric banding in adolescents: the Austrian experience.
AB  - BACKGROUND: Morbid obesity is a rising problem in adolescents in the industrial
      nations. Up to 25% of children have a body mass index (BMI) higher than the 85th
      age- and sex-adjusted percentile. Obesity in youth is associated with increased
      risk for morbidity and mortality in adulthood. In addition, these patients suffer
      from psychological problems and decreased quality of life. Bariatric procedures
      have shown effective long-term results in adults, but they are still discussed
      controversially in adolescent patients. METHODS: Between 1998 and 2004, 50
      adolescent patients with a mean age of 17.1+/-2.2 years (range 9-19 years)
      underwent laparoscopic adjustable gastric banding (LAGB) in Austria. The
      psychological changes were analyzed by using Moorehead-Ardelt/BAROS
      questionnaire. RESULTS: The mean BMI decreased from 45.2+/-7.6 kg/m2 at time of
      surgery to 32.6+/-6.8 kg/m2 after a mean follow-up of 34.7+/-17.5 months. The
      mean excess weight loss was 61.4+/-35.5%. Most of the adolescents showed
      remarkable improvements in their quality of life. The outcome was regarded as
      "excellent or very good" in 32 patients, "good" in 12 patients and "fair" in 5
      patients. Only one patient noticed no alterations after surgery. Two-thirds of
      the preoperative co-morbidities resolved, and one-third improved during follow
      up. Except for one port dislocation, no peri- or postoperative complications
      arose. CONCLUSION: LAGB is an effective and attractive treatment option in very
      carefully selected obese adolescents, because of its adjustability and the
      preservation of the gastrointestinal passage. The majority of patients showed a
      remarkable improvement in their quality of life.

PMID- 16901362
TI  - High ghrelin concentration is not a predictor of less weight loss in morbidly
      obese women treated with laparoscopic adjustable gastric banding.
AB  - BACKGROUND: We analyzed the role of high plasma ghrelin concentrations at surgery
      as a negative predictor of weight loss in morbidly obese patients treated with
      laparoscopic gastric banding (LAGB). METHODS: Fasting plasma ghrelin
      concentrations were measured in 113 women before LAGB, and 16 of them were
      identified as having ghrelin concentrations clearly higher than expected
      according to the BMI levels. The 2-year postoperative outcome of these 16
      patients was compared to the outcome of the remaining subjects. RESULTS: Mean
      fasting plasma ghrelin concentration in the group with hyperghrelinemia was
      82.3+/-23.1 pg/ml and in women with normal ghrelin was 27.1+/-11.3 pg/ml
      (P<0.001). No differences in age, age at onset of obesity or degree of obesity
      were observed between the two groups. Women with hyperghrelinemia had a weight
      gain during the waiting time similar to women with normal ghrelin. The prevalence
      of comorbidities and eating behavior disturbances was similar in the two groups,
      but depression was 2.5 fold more prevalent in the hyperghrelinemic women than in
      the women with normal ghrelin. The %EWL after LAGB surgery was similar in women
      with high and normal ghrelin concentrations, with no differences in levels of
      postoperative band filling. No differences in band-related complications or
      revisional surgery rate were observed between the two groups. CONCLUSION: A high
      fasting ghrelin concentration at baseline did not significantly affect the
      outcome after LAGB in morbidly obese women, in terms of weight loss and
      complications rate.

PMID- 16901363
TI  - Effects of laparoscopic pneumoperitoneum and changes in position on arterial
      pulse pressure wave-form: comparison between morbidly obese and normal-weight
      patients.
AB  - BACKGROUND: Laparoscopic adjustable gastric banding (LAGB) is commonly indicated
      in morbidly obese patients. There is controversy regarding the hemodynamic
      effects of pneumoperitoneum (PNP) in obese patients. PNP and changes in body
      posture have complex effects on venous return that may be detected by respiratory
      changes in the arterial pressure waveform. The aim of this study was to compare
      pneumoperitoneum-induced and reverse Trendelenburg (RT) changes in arterial pulse
      pressure in obese and normal-weight patients. METHODS: 15 morbidly obese patients
      undergoing LAGB were compared to 15 normal-weight patients undergoing
      laparoscopic surgery. Arterial pressure was non-invasively recorded using an
      arterial tonometer. Respiratory changes in pulse pressure (deltaPp) were recorded
      in the supine position without and with PNP, and in RT position with
      pneumoperitoneum. RESULTS: PNP increased deltaPp values in normal weight
      (P<0.001), but not in obese patients. RT position increased deltaPp values in
      obese patients, but did not cause additional changes in normal-weight patients.
      CONCLUSIONS: Unlike normal-weight patients, PNP in the supine position has
      minimal effect on the arterial pulse-pressure wave-form in obese patients. This
      observation may reflect physiological differences in total blood volume and
      loading conditions of the heart between morbidly obese and normal-weight
      patients, which affect venous return during PNP. Differences in abdominal
      vascular zone conditions between obese and normal weight-patients may explain
      these results.

PMID- 16901364
TI  - Total gastrectomy for complications of the duodenal switch, with reversal.
AB  - BACKGROUND: Duodenal switch (DS) is one of the most effective techniques for the
      treatment of morbid obesity and its related co-morbidities, with mortality rates
      of <1%, but with 9.4% morbidity rates (6.5% due to leaks). We present our
      experience with 9 patients operated with a DS, who later underwent total
      gastrectomy (TG) for complications of the sleeve gastrectomy. METHODS: From 1994
      to March 2006, 846 patients underwent the DS. 9 patients (1%) underwent TG; 5
      were due to gastric leak at the angle of His, 2 were related to leakage at the
      doudeno-ileal anastomosis (DIA), 1 was for stenosis of the gastric sleeve, and 1
      for a gastroparesis. In 3 cases, the DS was the second bariatric operation. Full
      restoration of bowel anatomy was attempted in all patients. RESULTS: TG has been
      the final solution for gastric complications of the DS in 9 (1%) of our 846
      patients. In all cases, bowel anatomy has been restored, and there was no
      mortality. Postoperative courses have been difficult and hospital stays have been
      long in all patients (mean 4.5 months; range 1-10 months), with several episodes
      of re-do surgery after the TG. The actual BMI and %EBMIL are acceptable.
      CONCLUSIONS: TG successfully treated all 9 cases with life-threatening
      complications and difficult reinterventions after DS, without mortality.
      Restoration of bowel anatomy was done in all cases, with good final results.

PMID- 16901365
TI  - Assessing sexual function in obese women preparing for bariatric surgery.
AB  - BACKGROUND: Obesity has become a modern epidemic, increasingly affecting the
      general population worldwide. Obese people are vulnerable to a variety of co
      morbidities, including cardiovascular and pulmonary disease, osteoarthritis,
      diabetes, cancer and psychiatric conditions, that not only diminish life
      expectancy but also impair quality of life. Research has shown that obesity is
      further linked to sexual dysfunction, although relevant studies are limited and
      further investigation is needed. METHODS: We assessed the sexual function of 60
      obese women scheduled to undergo bariatric surgery and 50 healthy controls
      matched by age, education and marital status. All participants were administered
      the Female Sexual Function Index (FSFI). Additionally, participants completed the
      Hospital Anxiety and Depression Scale (HADS). RESULTS: Obese women reported
      significant impairment on most domains of sexual function, including sexual
      desire, arousal, lubrication, orgasm, and satisfaction, compared to healthy
      controls. The observed sexual impairment was associated with BMI but was not
      entirely attributed to the presence of anxiety or depression. CONCLUSION: Obese
      women complain of significant sexual impairment. Obesity-related sexual
      dysfunction appears to be a complex condition linked to a range of social,
      psychological and biological factors. Clinicians are encouraged to evaluate
      routinely sexual function in this patient population in order to detect those who
      are in need of intervention.

PMID- 16901366
TI  - Laparoscopic sleeve gastrectomy for a super-super-obese patient with situs
      inversus totalis.
AB  - Situs inversus totalis is a rare defect which can present difficulties in the
      management in laparoscopic surgery due to the mirror-image anatomy. Herein, we
      report a patient with situs inversus totalis and super-super-obesity (BMI 76
      kg/m2). We performed successful laparoscopic sleeve gastrectomy. Technical
      details of this operation, with situs inversus totalis, are presented. There were
      no major difficulties compared to patients with usual anatomy. There are
      potential diseases associated with situs inversus and obesity; therefore, a
      careful investigation, including a chest x-ray and cardiac and abdominal
      ultrasounds should be performed before surgery. Sleeve gastrectomy is an adequate
      procedure in super-super-obese patients with situs inversus totalis.

PMID- 16901368
TI  - Retrograde intussusception following Roux-en-Y gastric bypass.
AB  - A case of retrograde intussusception is presented occurring >1 year following a
      Roux-en-Y gastric bypass (RYGBP). Presentation may be confusing and lead to a
      serious delay in diagnosis. Review of the literature shows most intussusceptions
      following RYGBP are retrograde, and most, if not all, appear to originate in the
      proximal common channel, as ours clearly did. The average excess body weight loss
      in these patients is much higher than expected, adding evidence that a
      dysmotility disorder is involved. A hypothesis is presented regarding the
      mechanism involved in these retrograde intussusceptions.

PMID- 16901367
TI  - Pulmonary embolus after retrieval of a temporary inferior vena caval filter in a
      Jehovah's Witness undergoing gastric bypass surgery.
AB  - We present the case of pulmonary embolus after retrieval of a temporary inferior
      vena caval (IVC) filter in a Jehovah's Witness patient who underwent uneventful
      laparoscopic gastric bypass surgery. The 40-year-old female was admitted to the
      hospital 2 days after retrieval of the filter with bilateral pulmonary emboli for
      which she received anticoagulation therapy and consequently developed thoracic
      bleeding. We present this complicated case to highlight the risk of pulmonary
      emboli after IVC filter removal without anticoagulation, and to demonstrate the
      additional risk in managing a Jehovah's Witness patient.

PMID- 16901369
TI  - Gastric bypass in a factor V deficient patient.
AB  - Factor V deficiency is a rare bleeding disorder requiring special attention
      during the peri-operative period. Surgical intervention in these patients can be
      technically challenging. Because of the rarity of this condition, the optimal
      management is unknown. Available literature supports peri-operative infusion of
      fresh frozen plasma. We report successful management of a factor V deficient
      patient undergoing Roux-en-Y gastric bypass. Literature review indicates that
      this is the first reported case of bariatric surgery in a patient with factor V
      deficiency.

PMID- 16901370
TI  - Gastric bypass surgery in a paraplegic morbidly obese patient.
AB  - The complications of spinal cord injury are exaggerated with obesity, and create
      complex medical and socioeconomic issues. Despite the well-documented advantages
      of bariatric surgery in reducing the morbidity of obesity, this option has not
      been routinely offered to obese patients with spinal cord injuries. We describe
      the first case of a morbidly obese male with a spinal cord injury who underwent a
      successful Roux-en-Y gastric bypass.

PMID- 16901371
TI  - Early gastric cancer found at preoperative assessment for bariatric surgery.
AB  - An association between gastric cancer and obesity has been suggested in large
      epidemiologic series. We present a 61-year-old lady with BMI 48.7 kg/m2, who
      underwent preoperative work-up for Roux-en-Y gastric bypass. Her endoscopy showed
      a depressed lesion at the incisura angularis, suggesting early gastric cancer.
      The biopsy confirmed well/moderately-differentiated adenocarcinoma. The surgical
      approach was subtotal gastrectomy leaving only part of the fundus, and was
      performed on an oncological basis, with lymphatic D2 dissection. The gastro
      enterostomy was 1.5 cm wide, and was constructed closer to the greater curvature
      over a 12-Fr Fouchet tube. The reconstruction was in a Roux-en-Y fashion, but the
      alimentary limb was 150 cm long. Despite the short follow-up, the way the surgery
      was conducted presumably maintained both oncologic and bariatric determinations.

PMID- 16901372
TI  - Obesity in the Neolithic era: a Greek female figurine.
AB  - In this paper, we present a female figurine made of clay, found in Farsala,
      Thessaly, Greece, and which is housed in the Athanassakeion Archaeological Museum
      of Volos, Greece. This Neolithic figurine has visible characteristics of female
      obesity and belongs to a class of figurines ironically named "Venuses". The
      figurine is described, and speculation underlying the reason for its construction
      and uses are presented. In addition, the historical and social background of the
      Prehistoric period is taken into consideration, in an attempt to evaluate the
      characteristics of ancient feminine obesity and compare it to its modern
      definitions.

PMID- 16901373
TI  - Staplerless laparoscopic gastric bypass: not so fast.

PMID- 16901375
TI  - Countermeasures for sleep loss and deprivation.
AB  - Sleep deprivation is ubiquitous and carries profound consequences in terms of
      personal and public health and safety. There is no substitute for a good night's
      sleep. Sleep that is optimal in quality and quantity for individuals, factoring
      in their age and personal sleep requirements, will minimize sleep debt and
      maximize daytime performance. Therefore, setting aside an adequate amount of time
      for sleep should be a priority; sleep should not be sacrificed at the expense of
      other activities of daily living. Nevertheless, there are certain therapeutic
      countermeasures available for individuals who are unable to obtain adequate sleep
      because of medical or sleep-related conditions (eg, narcolepsy, obstructive sleep
      apnea) when excessive daytime sleepiness is the main feature of the condition, or
      residual sleepiness despite treatment for the main conditions is present. These
      therapeutic countermeasures may also be considered in situations in which
      occupational constraints (eg, rotating shift work, military duty) dictate that
      constant or heightened vigilance is important or critical to work performance,
      crucial decision making, and/or survival. Exploration of the causes of sleep loss
      or deprivation, whether it is voluntary, or work or family induced, and/or the
      effects of a medical or sleep disorder, is a necessary first step in the
      evaluation of a patient who has significant daytime fatigue or sleepiness. Wake
      promoting substances and medications such as caffeine, modafinil,
      methylphenidate, and dextroamphetamine may be considered in situations in which
      sleep loss is unavoidable or persists despite treatment of an underlying disorder
      that is characterized by or associated with daytime fatigue or sleepiness.

PMID- 16901376
TI  - Treatment of sleep dysfunction and psychiatric disorders.
AB  - Patients with neurologic disorders commonly experience sleep dysfunction and
      psychiatric disorders. The most common sleep dysfunction is insomnia, which is a
      primary symptom in 30% to 90% of psychiatric disorders. Insomnia and fatigue are
      prominent symptoms of anxiety disorders and major depression, including patients
      who are treated but have residual symptoms. Anxiety and depressive disorders
      account for 40% to 50% of all cases of chronic insomnia. It is also recognized
      that primary insomnia and other primary sleep disorders produce symptoms that are
      similar to those reported by patients with psychiatric disorders. A clinician
      must judge whether sleep deprivation causes mood disturbance or whether
      depressive or anxiety disorder represents the primary reason for sleep
      dysfunction. When insomnia is comorbid with mild to moderate depression, therapy
      should begin with bedtime dosing of sedating antidepressants such as mirtazapine,
      nefazodone, or tricyclic antidepressants, which are preferred because of their
      sedative effects, although side effects may limit their usefulness. Intervention
      for chronic insomnia is similar in nonpsychiatric and psychiatric patients.
      Behavioral therapies, particularly cognitive behavioral therapy, and lifestyle
      changes show significant long-term efficacy as treatments for chronic insomnia.
      Sedative hypnotic agents are the most studied agents to treat insomnia,
      particularly those that are active through the benzodiazepine receptor-GABA
      complex, such as benzodiazepines, eszopiclone, zaleplon, and zolpidem. The new
      melatonin-receptor agonist ramelteon has not yet been studied in psychiatric
      patients. Prescription of adjunctive trazodone 50 to 150 mg is a common clinical
      practice to treat comorbid insomnia during antidepressant therapy, but published
      data are surprisingly limited when considered against the frequent usage of
      trazodone. Although there has been insufficient research on the use of atypical
      antipsychotic agents in severe insomnia, psychiatrists use quetiapine,
      olanzapine, or other agents to lessen agitation that disrupts sleep onset or
      maintenance. When insomnia or hypersomnia continues even as mood, anxiety, or
      thought disorders improve with standard therapy, the physician should consider
      the potential presence of underlying sleep disorders.

PMID- 16901377
TI  - Sleep dysfunction in women and its management.
AB  - Women generally have more complaints about sleep, compared with men of the same
      age. At various stages of reproduction, the reasons for these complaints become
      rather obvious--menstrual cramps and discomfort, pregnancy and postpartum
      factors, and menopausal hot flashes can fragment sleep. In addition, there are
      lifestyle factors, such as going to bed late and getting up early in order to
      attend to various family responsibilities, restricting the time allowed for
      sleep. Factors outside a woman's control, such as caregiving for sick family
      members during the night, can also result in disrupted sleep patterns, with
      little opportunity to make up for the lost sleep on weekends or days off. This
      article discusses the types of insomnia commonly experienced by women during key
      reproductive stages of life and proposes gender-specific assessment and
      management strategies. Pharmacologic management of sleep problems is useful for
      brief episodes of insomnia, but not usually desirable during pregnancy and
      lactation, or for management of chronic insomnia. For most women, regardless of
      reproductive stage, nonpharmacologic strategies that involve behavioral
      therapies, or short-term focused use of hypnotics at key time points, are more
      effective for quality of life than is long-term use of pharmacologic
      interventions.

PMID- 16901378
TI  - Treatment considerations in neuropathic pain.
AB  - Neuropathy is a relatively common source of acute and chronic pain. Emerging
      evidence suggests several pathophysiological mechanisms underlying the
      neuropathic pain associated with various disorders. Antidepressants and
      anticonvulsants have largely been the mainstay of treatment. Pharmacologic
      treatment of neuropathy frequently requires use of multiple medications. Ideally,
      the selection of which medications to use should be based on targeting the
      multiple pathophysiologic mechanisms contributing to neuropathic pain
      transmission. Psychological variables may play a role in predisposing patients to
      chronic neuropathy after acute illness. In addition, comorbid conditions,
      especially depression, can complicate the presentation, clinical course, and
      response to treatment of patients with chronic pain. Treatment of depression may
      be essential to fully enlist the chronic neuropathic pain patient in
      comprehensive pain management and rehabilitative approaches.

PMID- 16901379
TI  - Diagnostic and treatment interventions for hypochondriasis in the neurology
      setting.
AB  - Many patients who present to neurology settings with somatic complaints have
      underlying fear of illness, anxiety, or depression. Hypochondriasis, which is one
      of the somatoform disorders, contributes to high use of services and frustration
      on the part of clinicians, because diagnostic and treatment interventions often
      fail. The challenges for clinicians include how to distinguish true somatic
      symptoms from those associated with fear or other psychiatric symptoms. Our goal
      is to provide the clinician with an integrated approach for the triage,
      assessment (history, screening tools, examination, and diagnostic tests), and
      treatment of these challenging patients. Recommendations are made regarding
      psychiatric consultation and comanagement between fields for complex patients.

PMID- 16901380
TI  - Depression and quality of life issues in patients with amyotrophic lateral
      sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease that
      usually results in death secondary to respiratory failure. The psychological
      reaction to the diagnosis of ALS in patient and caregiver has received increasing
      attention. Reports are highly variable as to the severity of depressive symptoms
      in patients with ALS. When they exist, depressive symptoms can be managed with
      pharmacologic interventions. Recognizing cognitive impairment is essential in the
      management of patients with ALS. Quality of life assessments have been used to
      further evaluate the reaction to the disease. Maintaining a meaningful quality of
      life centers on psychological, supportive, and spiritual factors, as opposed to
      physical status. In addition to the patient's reaction, there are a variety of
      responses experienced by caregivers. Clinicians should provide appropriate
      support to the caregivers of the patients during the course of the illness and
      after death.

PMID- 16901381
TI  - Management of concussion and post-concussion syndrome.
AB  - Concussion and mild traumatic brain injury (mTBI) are common clinical problems.
      However, the literature is not consistent in defining how concussion and mTBI are
      related. Although most patients with concussion recover within days to weeks,
      approximately 10% develop persistent signs and symptoms of post-concussion
      syndrome (PCS). There are no scientifically established treatments for concussion
      or PCS and thus rest and cognitive rehabilitation are traditionally applied, with
      limited effectiveness. This article presents a clinical model to suggest that
      concussion evolves to become mTBI after PCS has developed, representing a more
      severe form of brain injury. The basic pathophysiology of concussion is
      presented, followed by a recommended approach to the clinical evaluation of
      concussion in the emergency department and the physician's office. We evaluate
      the limited evidence-based pharmacologic treatment of acute concussion symptoms
      and PCS symptoms and also discuss return to activity recommendations, with an
      emphasis on athletes. Lastly, we suggest a promising new direction for helping
      patients recover from PCS.

PMID- 16901383
TI  - Genetic advances in inflammatory bowel disease.
AB  - The translation of basic science advances to tangible benefits in clinical
      practice remains a fundamental goal of biomedical research. Genetic approaches
      provide a unique opportunity to enhance bench-to-bedside translational efforts,
      with inflammatory bowel disease (IBD) being a model genetic disorder in several
      respects. The association of the NOD2 (CARD15) mutations to Crohn's disease (CD)
      represents, in complex human disorders, one of the clearest cases of a definitive
      disease association. The NOD2 gene is located in the IBD1 genetic linkage region
      on chromosome 16 and functions as an intracellular pattern recognition receptor
      for components of bacterial peptidoglycan. CD-associated variants within NOD2
      have a decreased capacity to appropriately signal with peptidoglycan and provide
      an important example of gene-environment interactions. Genetic variation in other
      innate immune receptors, notably Toll-like receptor (TLR)4, has been defined and
      may also play a role in CD pathogenesis. Replicated CD association in the IBD5
      region on chromosome 5q has been reported, and candidate functional polymorphisms
      within the organic cation transporters OCTN1 (SLC22A4) and OCTN2 (SLC22A5) have
      been described. Confirmatory studies demonstrating altered OCTN activity and
      expression in primary human cells stratified on the IBD5 risk haplotype would
      provide important confirmatory support for disease contribution. A comprehensive
      understanding of IBD will involve integrating information from animal models,
      functional human polymorphisms, and expression studies from human IBD tissues.
      Genes and pathways implicated as contributing to IBD pathogenesis through
      multiple lines of evidence should be more intensively examined, including the
      tumor necrosis factor-alpha, MDR1, and peroxisome proliferator-activated receptor
      (PPAR)gamma pathways. To attain full advantage of new genetic information, novel
      methods of classifying patients that go beyond phenotypic classifications
      presently utilized will be required. Genetic data will need to be integrated with
      novel biomarker development in IBD, including functional, expression (mRNA or
      protein), or biochemical indicators of physiologic/disease processes and
      responses to therapies.

PMID- 16901382
TI  - Treating persistent adolescent aggression.
AB  - Adolescent aggressive behavior is a frequently encountered problem for clinicians
      and society as a whole. Better understanding of biological, social, and familial
      risk factors for maladaptive aggressive behavior may lead to more effective
      interventions. The social information processing problems characteristic of this
      group interfere with treatment and outcome. Although further studies are needed,
      evidence for the effectiveness of psychopharmacologic treatments is increasing.
      There is also evidence for several effective psychotherapeutic interventions,
      especially for those with affective/impulsive aggression. Knowledge of risk
      factors, psychosocial strategies, and psychopharmacologic treatments can enhance
      the clinician's ability to intervene with this difficult group.

PMID- 16901384
TI  - Novel biological therapies for inflammatory bowel disease.
AB  - The success of biological therapy is best advocated by infliximab (IFX), which
      has dramatically improved medical therapy for Crohn's disease and now has been
      shown to be effective in the treatment of ulcerative colitis. Other anti-tumor
      necrosis factor (TNF) compounds have been tested in the treatment of Crohn's
      disease and will soon appear in the therapeutic armament. However, neutralization
      of TNF does not seem to be the most important mechanism of action of these
      therapies. Apoptosis of activated T cells was demonstrated after IFX treatment,
      and this may be the key to its success. Thus, other therapies that induce
      apoptosis in activated T cells, such as visilizumab, have a great chance to be of
      benefit. Biological therapies applied in inflammatory bowel disease appear to be
      safe, although therapy-related adverse events clearly have been recognized.

PMID- 16901385
TI  - Colorectal cancer in inflammatory bowel disease: molecular and clinical
      considerations.
AB  - Adenocarcinoma of the colon is an accepted and feared complication of chronic
      ulcerative colitis (UC) and colonic Crohn's disease (CD). When cancer is
      identified, surgery is necessary, and unlike with sporadic colorectal cancer
      (CRC), in which partial colectomy is effective, proctocolectomy is required. As
      CRC is a rare complication of these diseases, studies of the pathogenesis are
      limited primarily to observational studies; thus, the mechanism and molecular
      events that lead to neoplastic change are not fully understood or well known.
      Precancerous dysplasia has been associated with concurrent or future CRC in UC
      and, although less studied, in CD, and is therefore considered a marker of cancer
      risk in inflammatory bowel disease (IBD). Risk factors for dysplasia and CRC in
      IBD include longer duration of disease, greater extent of disease, younger age at
      diagnosis, diagnosis with primary sclerosing cholangitis (PSC), family history of
      CRC, and possibly backwash ileitis and degree of inflammation of the bowel over
      time. Prevention of cancer in IBD has been focused on secondary measures of
      identifying dysplasia in flat mucosa or protruding lesions during surveillance
      colonoscopy with random biopsies and, when confirmed, performing proctocolectomy.
      Studies of primary prevention of dysplasia and CRC using chemopreventive agents
      have suggested a possible benefit with a number of agents. These include
      ursodeoxycholic acid (in patients with PSC and UC), aminosalicylates, and
      possibly statins.

PMID- 16901386
TI  - Safety of biologics in inflammatory bowel disease.
AB  - Various biologic agents have been evaluated in patients with inflammatory bowel
      disease (eg, Crohn's disease ) and ulcerative colitis (UC). At present, only one,
      infliximab (humanized monoclonal anti-tumor necrosis factor-alpha antibody), is
      approved by the US Food and Drug Administration for induction and maintenance
      treatment in patients with active moderate to severe and/or fistulizing CD who
      are refractory to conventional therapy. Two recent trials, Active Ulcerative
      Colitis Trial (ACT) 1 and ACT 2, observed high efficacy of infliximab in
      inducting and maintaining clinical remission, mucosal healing, and corticosteroid
      sparing effects in patients with moderate to severe UC. A plethora of randomized,
      double-blind, controlled and open-label, uncontrolled studies on large and small
      numbers of patients has assessed efficacy and safety of various biologic agents
      of potential use in treatment of inflammatory bowel disease. With respect to
      safety of biologic agents used for treatment, the most accurate data are
      available only in the case of infliximab. This is due to the fact that infliximab
      was evaluated in many more trials than any other biologic agent. Moreover,
      postmarketing experience also provides very valuable information about any side
      effects occurring during treatment with this agent.

PMID- 16901387
TI  - Management of refractory ulcerative colitis.
AB  - A physician's approach to patients with ulcerative colitis (UC) who are
      refractory to standard first-line therapies must be thoughtful and systematic and
      include the individual's physical and emotional state as the physician examines
      the various dietary, medical, and surgical options currently available. It is of
      foremost importance to confirm that the refractory patient's symptoms are not
      simply due to dietary indiscretion, concomitant bowel infection (especially with
      Clostridium difficile), an incorrect diagnosis (eg, colitis due to infection,
      NSAIDs, ischemia, diverticulitis, or Crohn's disease), or even a concomitant
      diagnosis (eg, celiac sprue, pancreatic insufficiency, functional bowel disorder,
      laxative or sorbitol intake). The ability to quickly assess the status of the
      colonic mucosa with flexible sigmoidoscopy aids in the ability to distinguish
      patients with refractory inflammation from those with other diagnoses. The
      initiation and optimization of the long-term purine analogues azathioprine (AZA)
      or 6-mercaptopurine (6-MP) remain the backbone of medical therapy for patients
      with refractory UC. For those unresponsive to corticosteroids, quicker induction
      of remission may necessitate infliximab, cyclosporine, or tacrolimus. Successful
      induction and maintenance with AZA, 6-MP, and/or infliximab should be followed by
      long-term therapy with these agents. Cessation of therapy often leads to relapse.
      Novel therapies under investigation hold the promise of offering more options for
      both the induction and maintenance of remission in refractory UC patients.
      Discussions of surgical intervention should not be put off as a last resort but
      rather included in the overall treatment plan offered to the patient.

PMID- 16901388
TI  - Neutropenic enterocolitis.
AB  - Neutropenic enterocolitis is a life-threatening gastrointestinal (GI)
      complication of chemotherapy most often associated with leukemia or lymphoma.
      Early recognition and treatment are essential for survival. The management of
      neutropenic enterocolitis is controversial. Neither prospective nor high-quality
      retrospective studies concerning medical or surgical therapies are available.
      Treatment approaches have been derived mostly from small case studies and
      retrospective reports. Therefore, a uniform management strategy cannot be
      recommended. The best strategy appears to be an individualized approach to each
      case given the wide spectrum of presentation. There is general agreement that
      early management should be conservative and should consist of bowel rest,
      intravenous fluid administration, total parenteral nutrition, broad-spectrum
      antibiotics, and normalization of neutrophil counts. Surgical intervention is
      warranted in the setting of perforation, obstruction, clinical deterioration
      suggestive of uncontrolled sepsis, and persistent GI bleeding despite correction
      of cytopenias and coagulopathy.

PMID- 16901389
TI  - Laparoscopic treatment of colorectal neoplasia.
AB  - A recent major advance in the surgical treatment of colorectal cancer has been
      the introduction of laparoscopic surgery. Laparoscopic colectomy is associated
      with decreased postoperative pain, faster ileus resolution, shorter hospital
      stay, improved cosmesis, and decreased morbidity when compared with open
      colectomy. However, early reports of high rates of laparoscopic wound metastases
      gave rise to questions regarding the adequacy of the laparoscopic technique for
      curative resection of malignancies. These concerns over oncologic outcomes are
      addressed by several single and multi-institutional randomized trials in the
      United States and throughout the world that have compared laparoscopic-assisted
      colectomy with conventional open colectomy. These studies have established both
      the short- and long-term safety and oncologic efficacy of laparoscopic colectomy
      for cancer. To ensure successful outcomes, surgeons performing laparoscopic
      colectomy should be adequately experienced. Limitations include the technical
      requirements of advanced laparoscopic skills and training, increased operative
      time, and equipment costs. Despite these limitations, patient recovery benefits
      may offset the increased operative costs and result in improved outcome overall.

PMID- 16901390
TI  - Update on Clostridium difficile.
AB  - The most dramatic change in the past several years has been the increased
      incidence and severity of Clostridium difficile colitis reported from multiple
      countries. A number of factors have likely contributed to this. One major event
      has been the emergence of a fluoroquinolone-resistant clone of C. difficile with
      enhanced virulence properties that is associated with epidemic disease. Also
      noteworthy is the apparently decreasing effectiveness of the first-line agent
      metronidazole in treating this disease. Aggressive treatment of severe C.
      difficile colitis requires a multifaceted approach, including: 1) cessation of
      antibiotics where possible; 2) oral vancomycin; 3) if an ileus exists,
      intravenous administration of metronidazole and possibly intracolonic
      administration of vancomycin; 4) intravenous immunoglobulin if response to
      therapy is not rapid, or if there are signs of sepsis; and 5) early surgical
      consultation. Although it is likely that intravenous immunoglobulin contains
      antibodies against C. difficile toxins, its benefit remains unproven in rigorous
      clinical trials. Efforts to actively or passively immunize patients at risk are
      being explored to prevent the increasing morbidity and mortality associated with
      this disease. However, defining exactly who is at risk for severe C. difficile
      associated disease is complex, as cases are being reported in populations not
      previously believed to be vulnerable.

PMID- 16901391
TI  - Adjuvant Therapy for Stage II Colorectal Cancer: Who and with What?
AB  - The role of adjuvant chemotherapy for patients with stage II colon adenocarcinoma
      remains controversial. The high surgical cure rate for patients with "low-risk"
      stage II colon cancer, ranging from 75% to 80%, and the available clinical trials
      and meta-analyses provide conflicting recommendations for or against adjuvant
      chemotherapy for this group of patients. For fit "high-risk" stage II patients
      with clinical obstruction or perforation at presentation, in which the 5-year
      survival rate is 60% to 70%, there is little controversy, as these patients are
      routinely treated with adjuvant chemotherapy. Other potential high-risk factors,
      including high histologic grade, microsatellite instability, and loss of 18q,
      have yet to be validated in prospective trials. Patients with fewer than 12
      regional lymph nodes identified in the surgical specimen have a statistically
      unclear risk of lymph node involvement. These patients may have stage III disease
      and should receive adjuvant therapy. The decision to use adjuvant chemotherapy to
      treat low-risk stage II colon cancer patients (no obstruction or perforation)
      should be an informed decision weighing the magnitude of a net 2% to 5% survival
      benefit, a 0.5% to 1.0% risk of mortality with chemotherapy in addition to 6
      months of chemotherapy-related toxicities, other coexisting patient morbidities,
      and the anticipated life expectancy of each patient. As adjuvant chemotherapy is
      therapy addressing local or metastatic microscopic disease, and the effectiveness
      of systemic and biologically targeted therapy for advanced macroscopic colon
      cancer continues to improve rapidly, it remains to be determined by clinical
      trials whether therapies including newer agents such as cetuximab and bevacizumab
      administered in the adjuvant setting may affect survival for stage II cancer
      patients.

PMID- 16901392
TI  - The "new" era of oral antineoplastic drug therapy: revisiting "old" concerns.

PMID- 16901393
TI  - Clinical trials report. Minimal residual disease quantification in adult acute
      lymphoblastic leukemia.

PMID- 16901394
TI  - Novel approaches in allogeneic stem cell transplantation.
AB  - Allogeneic transplantation remains an integral part of the management of
      hematologic malignancies. However, transplant-related mortality, graft-versus
      host disease, and disease recurrence continue to be major limitations to
      successful transplant outcomes and challenges to investigators in the field.
      Newer approaches have focused on reduction of the intensity of the conditioning
      regimens, harnessing the antitumor effects of the allograft, and development of
      adoptive immunotherapy strategies to circumvent the limitations. These
      developments provide physicians with the ability to tailor transplants to
      specific patients and their diseases.

PMID- 16901395
TI  - Philadelphia chromosome-positive acute lymphoblastic leukemia: impact of imatinib
      treatment on remission induction and allogeneic stem cell transplantation.
AB  - Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) has
      been associated with the worst patient survival rates of the various acute
      leukemias. Imatinib mesylate is a novel therapeutic agent that targets the BCR
      ABL tyrosine kinase, the molecular abnormality associated with Ph+ ALL. The
      combination of imatinib with chemotherapy has led to improved and durable
      treatment responses in adult patients with Ph+ ALL, including the elderly
      population. Hematopoietic stem cell transplantation has also integrated imatinib
      into its transplant strategies, with early data suggesting improved progression
      free survival without clearly identifiable augmented toxicity. Second-generation
      tyrosine kinase inhibitors offer potentially even greater improvements on these
      excellent imatinib-associated outcomes. This review addresses the evolution of
      the management of Ph+ ALL and is intended to assist in the description of its new
      natural history.

PMID- 16901396
TI  - Clinical trials report. Comparison of ABVD chemotherapy and a regimen including
      radiation therapy in patients with limited-stage non-Hodgkin's lymphoma.

PMID- 16901397
TI  - Clinical and molecular prognostic factors in follicular lymphoma.
AB  - The observed variability in the clinical course of follicular lymphoma (FL),
      along with the diverse range of therapeutic options available, necessitates
      accurate prognostic stratification of the individual patient. A number of
      clinical, laboratory, and pathologic parameters have been associated with both
      good and poor risk disease; in some instances these have been incorporated into
      readily calculable prognostic indices. With new insights into disease biology and
      the resulting identification of biomarkers that have arisen from the analysis of
      both the genome and the transcriptome, more accurate individualization of
      prognosis will be realized. At present the clinical application of such
      biomarkers, however, remains largely in its infancy. This review examines the
      clinical and molecular prognostic features that have been identified as of value
      in FL.

PMID- 16901398
TI  - Investigational strategies in autologous stem cell transplantation for follicular
      lymphoma.
AB  - Recent retrospective analyses indicate prolonged survival for patients with
      follicular lymphoma over the past 25 years, attributed most likely to improved
      supportive care and sequential application of effective therapies. Encouraging
      results were obtained from several randomized trials evaluating myeloablative
      therapy followed by autologous stem cell transplantation (ASCT) as consolidation
      therapy applied to patients with advanced-stage follicular lymphoma either in
      first remission or as salvage therapy. However, because of the successful
      introduction of rituximab to the standard therapeutic repertoire, with its long
      term beneficial clinical impact, ASCT must be reevaluated in prospective clinical
      trials, especially taking into account the potential short- and long-term
      toxicity associated with high-dose therapy. The concept of in vivo purging before
      or after ASCT and the introduction of radioimmunotherapy as part of the
      myeloablative regimen may further improve treatment results, reduce toxicity, and
      increase applicability. Combination of these novel strategies into a multimodal
      approach justifies hope that the treatment outcome of patients suffering from
      follicular lymphoma will be further improved.

PMID- 16901399
TI  - Mycosis fungoides and sezary syndrome: an update.
AB  - Mycosis fungoides (MF), and the associated leukemic variant Sezary Syndrome (SS),
      are the most common group of cutaneous T-cell lymphomas. MF/SS is a non-Hodgkin's
      lymphoma of mature, skin-homing, clonal, malignant T lymphocytes that initially
      presents in the skin as patches, plaques, tumors, or generalized erythema
      (erythroderma) and can involve the lymph nodes and peripheral blood. Much
      progress has been made in recent years in understanding the origin of the
      malignant T cell in MF/SS and the pathophysiology and immunology of the disease.
      This recent work has made a great impact on diagnosis, prognostication, and
      treatment. In this review, we survey the MF/SS published literature over the past
      year and highlight some of the important advances.

PMID- 16901401
TI  - Clinical trials report. Sun exposure and mortality from melanoma.

PMID- 16901400
TI  - Non-Hodgkin's lymphoma in children and adolescents.
AB  - Lymphoma is the third most common cancer in children and adolescents. Non
      Hodgkin's lymphomas comprise a heterogeneous group of tumors with distinct
      pathologic and clinical characteristics. Over the past three decades, significant
      advancements have been made in the molecular characterization of these disorders.
      With the use of intensive multiagent chemotherapy, non-Hodgkin's lymphomas are
      now among the most successfully treated cancers in the pediatric population.
      Future goals of therapy include reduction of treatment duration for early-stage
      patients and identification of novel targets and therapeutics for advanced-stage
      patients.

PMID- 16901402
TI  - Therapeutic targets in melanoma: map kinase pathway.
AB  - Recent progress in our understanding of the genetic alterations that occur in the
      pathogenesis of melanoma provides exciting opportunities for therapy. The most
      important signaling pathways in melanoma lie downstream of NRAS: the RAS-BRAF
      MAPK pathway. A great deal of attention has been focused on the high mutation
      rate in the BRAF oncogene, which approaches 60%, because BRAF itself is an
      appealing drug substrate and because of the central contribution of BRAF function
      to melanoma development that the mutation rate signifies. Agents that
      specifically target BRAF, such as sorafenib, as well as new molecules that
      function both upstream and downstream of BRAF, are being actively investigated.

PMID- 16901403
TI  - Complex "cross talk" involving nitric oxide metabolites: who's listening?

PMID- 16901405
TI  - Fibrate therapy in patients with metabolic syndrome and diabetes mellitus.
AB  - Patients with metabolic syndrome and type 2 diabetes mellitus are usually in
      moderately high-risk, high-risk, or very high-risk cardiovascular categories and
      present major therapeutic challenges. The dyslipidemia in such patients is
      typically a disorder of the triglyceride/high-density lipoprotein axis (TG/HDL
      axis) characterized by an excess of triglyceride-rich lipoproteins and a
      reduction of HDL. Very often, lifestyle therapy and statin monotherapy fail to
      achieve guideline goals, necessitating combination therapies. Fibric acids (or
      fibrates), are agonists of peroxisome proliferator-activated receptor alpha,which
      have amassed significant lipid-surrogate and clinical outcome trial data,
      especially in insulin-resistant patients, typical of those with metabolic
      syndrome or type 2 diabetes mellitus. Current guidelines advocate fibrate use as
      an add-on to statin therapy when TG/HDL abnormalities exist in such patients. In
      this paper, we review pertinent and recent trial data, mechanisms of action, and
      the safety of fibrate therapy.

PMID- 16901406
TI  - Apolipoprotein A-I and risk for cardiovascular diseases.
AB  - Increased concentrations of high-density lipoprotein (HDL) cholesterol have been
      closely associated with decreased risk of future cardiovascular disease. This
      protective effect of HDL has been mainly attributed to its involvement in reverse
      cholesterol transport. More recently, it has been suggested that apolipoprotein A
      I (apoA-I), the major protein component of HDL, possesses nearly identical
      information as HDL in terms of risk prediction for future cardiovascular disease.
      This makes apoA-I a very attractive biomarker candidate for implementation into
      clinical practice, taking into account its analytical advantages. This review
      summarizes our current knowledge based on observations from recent studies, with
      emphasis on potential pathophysiologic mechanisms of action and on the clinical
      utility of apoA-I as a predictor of cardiovascular risk.

PMID- 16901407
TI  - Lipoprotein-associated phospholipase A2: pathogenic mechanisms and clinical
      utility for predicting cardiovascular events.
AB  - Lipoprotein-associated phospholipase A(2 )(Lp-PLA(2)), a member of the
      phospholipase superfamily, circulates primarily bound to low-density lipoprotein
      and has been associated with cardiovascular disease risk in epidemiologic
      studies. However, it has not been established whether Lp-PLA(2) is a risk marker
      or a risk factor. Identification of individuals with elevated Lp-PLA(2) may
      improve risk assessment, and Lp-PLA(2) may also provide an additional target of
      therapy. Statin therapy has been shown to reduce Lp-PLA(2), and selective
      inhibitors of Lp-PLA(2) are under development. Additional research is needed to
      further determine the role of Lp-PLA(2) in atherogenesis and atherothrombotic
      events.

PMID- 16901408
TI  - Are lower levels of low-density lipoprotein cholesterol beneficial? a review of
      recent data.
AB  - In the 1960s, epidemiologic studies established a link between elevated serum
      cholesterol and increased risk of cardiovascular events. Extensive clinical trial
      data subsequently highlighted 3-hydroxy-3-methylglutaryl coenzyme A reductase
      inhibitors (ie, statins) as the most effective pharmacotherapy for lowering low
      density lipoprotein (LDL) cholesterol, and showed that statin-mediated LDL
      cholesterol reductions were associated with significant improvements in
      cardiovascular outcomes. Such findings are reflected in current cardiovascular
      disease management guidelines, which focus on LDL cholesterol as the primary
      therapeutic target. These guidelines recommend target LDL cholesterol levels.
      However, a number of clinical trials have failed to identify an LDL cholesterol
      threshold level below which no further cardiovascular risk reduction occurs. Such
      findings suggest that optimal risk reduction may require greater reductions in
      LDL cholesterol than are currently being achieved. This review examines recent
      data highlighting the benefits of more pronounced LDL cholesterol reductions and
      considers how this could be achieved in clinical practice when many patients are
      not even reaching current targets.

PMID- 16901409
TI  - Statins and the primary prevention of cardiovascular events.
AB  - Cardiovascular disease remains the leading cause of death in both men and women
      in the United States. Treating elevated low-density lipoprotein (LDL) cholesterol
      has been shown to be very effective in reducing the rate of coronary heart
      disease (CHD) in primary prevention trials; however, the data are not as robust
      for treating individuals categorized at either lower risk for CHD or with below
      average LDL cholesterol levels. The next frontier for investigation will include
      strategies to determine who in these lower risk categories should be treated with
      statins. The growing epidemics of obesity, diabetes, and metabolic syndrome also
      loom as major problems that need to be incorporated into any strategy that
      focuses on the prevention of cardiovascular disease. In individuals with multiple
      cardiovascular risk factors, combination therapies tailored to address each
      individual's risk profile need to be considered to best decrease the likelihood
      of their first coronary event.

PMID- 16901410
TI  - Impact of thiazolidenediones on serum lipoprotein levels.
AB  - The thiazolidinediones, acting through peroxisome proliferator-activated receptor
      chi (PPARchi), affect multiple areas of metabolism. Of increasing importance is
      the recognition that these agents affect lipoprotein metabolism and cause changes
      in serum lipid and lipoprotein levels. All three thiazolidinediones, including
      troglitazone (which was withdrawn in the year 2000), rosiglitazone, and
      pioglitazone, tend to increase high-density lipoprotein (HDL) cholesterol,
      increase the size/decrease the density of low-density lipoprotein (LDL)
      particles, and raise the level of lipoprotein(a). In addition, troglitazone and
      pioglitazone, but not rosiglitazone, lower triglyceride levels modestly, thereby
      further contributing to increases in LDL and HDL size. The mechanism for these
      effects is still being clarified, but may involve enhancement of triglyceride
      clearance (in the case of pioglitazone), alteration of apolipoprotein C-III
      levels, reduction of hepatic lipase, and increase in ATP binding cassette A1
      (ABCA1) activity. The clinical implications of these effects need further
      exploration.

PMID- 16901411
TI  - High-density lipoprotein: is it always atheroprotective?
AB  - High-density lipoproteins (HDLs) are appropriately recognized for their many
      atheroprotective functions, including reverse cholesterol transport, as well as
      antioxidant, anti-inflammatory, and antithrombotic effects. Furthermore, the
      inverse relationship between HDL cholesterol and atherosclerosis is well
      documented in many populations. However, there is an increasing body of evidence
      that there are circumstances in which HDL may not be protective, and may in fact
      paradoxically promote vascular inflammation and oxidation of low-density
      lipoproteins. Recent studies have provided insight as to specific chemical
      modifications and structural changes within HDL associated with this phenotype.
      The presence of proinflammatory HDL coincides with conditions associated with
      chronic systemic inflammation, including atherosclerosis.

PMID- 16901412
TI  - Clinical insights into the diagnosis and management of atherosclerotic renal
      artery disease.
AB  - Atherosclerotic renovascular disease (ARVD) is an increasingly common contributor
      to hypertension and renal failure. However, not all patients with an identified
      obstructive atherosclerotic renal artery stenosis will have clinical improvement,
      even after successful percutaneous intervention. As such, there remains extensive
      controversy regarding optimal diagnostic and treatment strategies. Part of this
      controversy is the result of a paucity of well-designed prospective, randomized
      clinical trials, but the complex nature of the disorder and the heterogeneity of
      patients presenting with possible ARVD make simple diagnostic and treatment
      paradigms difficult to develop. This narrative review describes the latest
      observations concerning the prevalence, pathogenesis, natural history, diagnostic
      studies, and treatment options for suspected ARVD. Hopefully, this knowledge will
      improve the ability of clinicians to weigh risks and benefits and determine the
      best strategy in individual patients.

PMID- 16901413
TI  - C-reactive protein and cardiovascular disease: weighing the evidence.
AB  - C-reactive protein (CRP) has been widely promoted as a strong, independent
      predictor of cardiovascular events and metabolic syndrome, both in general
      populations and in patients with clinical cardiovascular disease, and as a causal
      player in atherothrombosis. However, recent evidence shows that the association
      of CRP with cardiovascular events is weaker than previously thought, that it may
      be largely attributed to confounding by established causal risk factors, and that
      CRP is, therefore, probably not a clinically useful risk predictor. The lack of
      association of noncoding CRP gene polymorphisms (which determine different
      baseline CRP values) with coronary events or metabolic syndrome does not support
      a causal role for CRP, and most of the putatively proatherothrombotic in vitro
      effects claimed for CRP were caused by contaminants in commercial CRP
      preparations and not by CRP. Future clinical trials of specific CRP inhibitors
      now in development could directly test the contribution of CRP to pathogenesis of
      cardiovascular disease.

PMID- 16901414
TI  - The CARDS trial: diabetic patients dealt a winning hand.
AB  - Until recently, the role of statin therapy in diabetic patients without clinical
      signs or symptoms of coronary heart disease had been inadequately defined. The
      Collaborative Atorvastatin Diabetes Study (CARDS) is a prospective, randomized,
      placebo-controlled trial designed to compare the effects of atorvastatin with
      placebo in preventing primary coronary events in diabetic patients. After a
      median of only 3.9 years (the study was terminated approximately 2 years early
      due to the magnitude of benefit attributable to atorvastatin therapy), risk for
      major cardiovascular events was decreased by 37%, acute coronary heart disease
      related events were also reduced by 36%, coronary revascularizations by 31%, and
      stroke by 48%. Benefit emerged within 1 year of initiating therapy.

PMID- 16901415
TI  - Hypoadiponectinemia: a common basis for diseases associated with overnutrition.
AB  - Adiponectin is a plasma protein derived from adipose tissue, which we discovered
      from a human adipose cDNA project. Adiponectin exists in circulating plasma at
      concentrations ranging from 4 to 30 microg/mL, which is much higher than the
      concentrations of various other hormones and cytokines. Adiponectin has a sticky
      nature, binding to collagen I, III, and V, which are present in vascular intima.
      Adiponectin exhibits various antiatherogenic effects on vascular cells,
      suppressing the expression of adhesion molecules in vascular endothelial cells,
      proliferation of smooth muscle cells, and cholesteryl-ester accumulation in
      macrophages. However, its plasma levels are low in subjects with excess intra
      abdominal fat. Adiponectin also has antidiabetic properties, and plasma
      adiponectin levels correlate positively with insulin sensitivity. Several
      clinical studies have demonstrated that hypoadiponectinemia is a risk factor for
      new-onset diabetes. Recent studies suggest that hypoadiponectinemia may partly
      contribute to the development of salt-sensitive hypertension and hypertensive
      heart failure, and can be also a risk factor for overnutrition-related cancers
      such as breast, colon, uterine, and prostate cancers. Hypoadiponectinemia might
      be at least in part the molecular basis of various diseases associated with
      overnutrition.

PMID- 16901416
TI  - John Rees Roberts.

PMID- 16901417
TI  - Cyclic vomiting syndrome plus.
AB  - Cyclic vomiting syndrome, which is characterized by severe discrete episodes of
      nausea, vomiting, and lethargy, is a fairly common, disabling, predominately
      childhood condition. Approximately 25% of cases have coexisting neuromuscular
      disease manifestations (cyclic vomiting syndrome plus). To determine whether
      patients with cyclic vomiting syndrome and neuromuscular disease represent a
      distinct subentity within cyclic vomiting syndrome, a clinical interview was
      conducted regarding 80 randomly ascertained sufferers of cyclic vomiting syndrome
      from a disease association database. Cyclic vomiting syndrome plus and "cyclic
      vomiting syndrome minus," herein defined as the presence of at least two and zero
      neuromuscular disease manifestations, were present in 23 and 44 subjects,
      respectively. Neuromuscular disease manifestations, including cognitive
      disorders, skeletal myopathy, cranial nerve dysfunction, and seizure disorders,
      were found to statistically cluster together among the same subjects. In
      addition, subjects with cyclic vomiting syndrome with neuromuscular disease had
      an earlier age at onset for vomiting episodes and a three- to eightfold
      statistically increased prevalence for certain dysautonomia-related (migraine,
      chronic fatigue, neurovascular dystrophy) and constitutional (growth retardation
      and birth defects) disorders. However, subjects with cyclic vomiting syndrome
      with and without neuromuscular disease were equally likely to have a sibling
      affected with neuromuscular disease manifestations. We conclude that cyclic
      vomiting syndrome plus, although likely not genetically distinct from cyclic
      vomiting syndrome minus, represents a distinct phenotypic entity that predicts an
      earlier onset of disease and increased comorbidity with a distinct list of
      medical conditions, possibly owing to a higher degree of mitochondrial
      dysfunction.

PMID- 16901418
TI  - Safety of high-dose botulinum toxin type A therapy for the treatment of pediatric
      spasticity.
AB  - This retrospective chart review examines the safety of high-dose (> or = 15 U/kg
      body weight or > or = 800 total units) botulinum toxin type A (BOTOX, Allergan
      Inc., Irvine, CA) in children and young adults with spasticity. Ninety-four
      children weighing < 45 kg received a mean total dose of 334.1 U or 19.1 U/kg.
      Fourteen young adults weighing > or = 45 kg received a mean total dose of 927.3 U
      or 15.2 U/kg. Adverse events were reported by 3 of the 108 patients (2.8%) and
      included single instances of rash and enuresis. The only serious adverse event
      consisted of mild, generalized botulism in a 13-year-old patient who received a
      23 U/kg dose to the hamstrings and gastrocnemius/soleus bilaterally. No serious
      adverse events were noted in children weighing < 45 kg who received botulinum
      toxin type A doses of 15 to 22 U/kg of body weight or in young adults > or = 45
      kg who received total doses of 800 to 1200 U in a single injection protocol. High
      dose botulinum toxin type A is safe for the treatment of spasticity in children
      and young adults.

PMID- 16901419
TI  - Efficacy of the ketogenic diet as a treatment option for epilepsy: meta-analysis.
AB  - The evidence base for the efficacy of the ketogenic diet was assessed among
      pediatric epileptic patients by application of a rigorous statistical meta
      analysis. Nineteen studies from 392 abstracts met the inclusion criteria. The
      sample size was 1084 patients (mean age at initiation 5.78 +/- 3.43 years). The
      pooled odds ratio, using a random effects model, of treatment success (> 50%
      seizure reduction) among patients staying on the diet relative to those
      discontinuing the diet was 2.25 (95% confidence interval = 1.69-2.98). The
      reasons for diet discontinuation included < 50% seizure reduction (47.0%), diet
      restrictiveness (16.4%), and incurrent illness or diet side effects (13.2%). The
      results indicate that children with generalized seizures and patients who respond
      with > 50% seizure reduction within 3 months tend to remain on the diet longer.
      Although no class I or II studies have been published regarding the efficacy of
      the ketogenic diet, this meta-analysis shows that current observational studies
      reporting on the therapeutic effect of the ketogenic diet contain valuable
      statistical data. Future observational studies should aim for long-term follow
      up, patient dropout analysis, and improved seizure type characterization.

PMID- 16901420
TI  - Study of the relationship between tuberous sclerosis complex and autistic
      disorder.
AB  - There has been increasing awareness that there are behavioral phenotypes in
      tuberous sclerosis complex with neuropsychiatric symptom complex such as autistic
      disorder and attention-deficit hyperactivity disorder (ADHD). However, the
      neurobiologic basis of autistic disorder in tuberous sclerosis complex is still
      unknown. We studied two cohorts of children followed up since 1986 until 2003,
      one cohort with tuberous sclerosis complex and another cohort with autistic
      disorder, to determine the incidence of autistic disorder in tuberous sclerosis
      complex and the incidence of tuberous sclerosis complex in autistic disorder
      respectively. We established a Tuberous Sclerosis Complex Registry in 1985 at the
      University of Hong Kong. In 2004, 44 index cases (the male to female ratio was
      0.75:1) were registered. Three had a positive family history of tuberous
      sclerosis complex. Thus, the total number of tuberous sclerosis complex cases was
      47. We adopted the diagnostic criteria of tuberous sclerosis complex for case
      ascertainment. The period prevalence rate of tuberous sclerosis complex for
      children and adolescents aged < 20 years is 3.5 per 10,000 (on Hong Kong island,
      excluding the eastern region with 125,100 aged < 20 years in 2003). Of 44 cases
      with tuberous sclerosis complex, 7 had autistic disorder. Thus, the incidence of
      autistic disorder in tuberous sclerosis complex is 16%. During the 17-year period
      (1986-2003), we collected a database of 753 children (668 boys and 84 girls; male
      to female ratio 8:1) with autistic disorder and pervasive developmental
      disorders. For all children with autistic disorder or pervasive developmental
      disorders, we routinely examined for any features of tuberous sclerosis complex
      by looking for neurocutaneous markers such as depigmented spots, which appear in
      50% of children with tuberous sclerosis complex by the age of 2 years. For those
      with infantile spasm or epilepsy, the clinical features of tuberous sclerosis
      complex were monitored regularly during follow-up. Of these, seven had tuberous
      sclerosis complex. Thus, the incidence of tuberous sclerosis complex in autistic
      disorder is 0.9%. All of these children are mentally retarded, with moderate to
      severe grades in an intellectual assessment conducted by a clinical psychologist.
      Future studies should be directed toward looking at the various behavioral
      phenotypes in tuberous sclerosis complex and defining these with standardized
      criteria to look for any real association with the underlying genetic mutation of
      TSC1 or TSC2 gene or even the site of tubers in the brain.

PMID- 16901421
TI  - Effects of anticonvulsant therapy on vitamin D status in children: prospective
      monitoring study.
AB  - Reports of hypovitaminosis D associated with anticonvulsant drugs in pediatric
      patients are conflicting. The effects of carbamazepine or sodium valproate on
      vitamin D status were evaluated prospectively in 51 ambulatory epileptic children
      who were followed during the first year of the study and in 25 and 6 children
      during the second and third year, respectively. Serum 25-hydroxyvitamin D,
      parathyroid hormone, calcium, and phosphorus levels were determined before and
      every 3 months during anticonvulsant therapy. Our subjects were grouped into four
      classes (0, 1, 2, and 3 consisted of the patients before and during the first,
      second, and third years of the treatment, respectively). The control group
      consisted of 80 healthy children. Comparisons between controls and patients of
      class 0 for the means for each season of all variables showed no significant
      differences. A decreasing trend in serum 25-hydroxyvitamin D (P < .03) and an
      increasing trend in serum parathyroid hormone (P < .04) levels were noticed in
      all seasons from class 0 to class 3. Twenty-five patients (49%) acquired
      hypovitaminosis D during the study period. The effects of seasonality on serum 25
      hydroxyvitamin D, parathyroid hormone, and calcium were noticed in our patients
      grouped in classes 0, 2 and 3, as well as in controls. Evidence is provided that
      carbamazepine or sodium valproate can cause hypovitaminosis D in children.

PMID- 16901422
TI  - Deep sedation with propofol in patients with Rett syndrome.
AB  - Herein we present the largest retrospective case-control series of deep sedation
      in patients with Rett syndrome, including discussion of the unique aspects of
      Rett syndrome that make these patients at high risk of sedation. Twenty-one
      patients with Rett syndrome and 21 control patients who received propofol for
      deep sedation to facilitate lumbar puncture were compared. Patients with Rett
      syndrome required significantly less propofol than control patients when
      standardized for weight and the duration of the procedure (P = .004). Seven of
      the 21 patients with Rett syndrome compared with none of the control patients
      experienced a serious adverse event, most of which were due to prolonged apnea (P
      = .004). All adverse events were transient, and all patients returned to their
      baseline after the procedure was completed. Sedation of patients with Rett
      syndrome is associated with a relatively high rate of complications and should
      not be done without appropriate personnel available who recognize the risks of
      sedating this unique population.

PMID- 16901423
TI  - Adolescents' perception of epilepsy compared with other chronic diseases:
      "through a teenager's eyes".
AB  - Adolescent perception of physical and social impact of chronic illness was
      assessed to determine (1) if there is greater prejudice toward epilepsy than
      other chronic disease and (2) if adolescents with chronic disease have less
      prejudice toward similarly affected peers with all types of chronic disease or
      just their specific chronic disease. Cognitively normal teens aged 13 to 18 years
      without chronic disease (n = 41) and with epilepsy (n = 32), asthma (n = 38),
      diabetes (n = 21), and migraine (n = 17) were interviewed in the outpatient
      clinics of a tertiary care pediatric center regarding their perceptions of the
      physical and social impact of eight chronic diseases (epilepsy, asthma, diabetes,
      Down syndrome, arthritis, migraine, leukemia, human immunodeficiency virus [HIV]
      infection). Epilepsy was perceived to have a more adverse physical impact than
      all chronic illnesses except Down syndrome. The perception was that it more
      frequently caused mental handicap, injured the afflicted individual and
      bystanders, and led to death. Epilepsy was also perceived to have a more negative
      social impact, particularly on behavior, honesty, popularity, adeptness at
      sports, and fun. Significantly more adolescents expressed reluctance to befriend
      peers with epilepsy, both from their own and their perceived parental
      perspectives. Having a chronic disease did not generally alter the adolescents'
      perceptions of peers with chronic disease. However, cases with epilepsy ranked
      this disease to have less social impact than teens with other chronic diseases.
      In conclusion, adolescents consider epilepsy to have a greater physical and
      social impact than most chronic diseases. Educational efforts should focus on the
      "normality" of most persons with epilepsy and emphasize the low risk of injury
      when proper first aid is followed.

PMID- 16901424
TI  - Clinical characteristics of childhood-onset (juvenile) Huntington disease: report
      of 12 patients and review of the literature.
AB  - Whereas adult-onset Huntington disease is a well-characterized clinical entity,
      childhood-onset cases have not received as much attention. In this report, the
      clinical, demographic, and genetic characteristics in 12 patients with childhood
      onset Huntington disease are presented and compared with data in the literature.
      The patients were divided into two groups based on age at onset of symptoms (< 10
      or > or = 10 years old). The majority of patients had onset of symptoms before 10
      years of age and most at or below 5 years of age. The delay in diagnosis was
      longer in those with earlier onset of symptoms. Inheritance was paternal in all
      patients with onset beyond 10 years of age. We found a preponderance of male
      patients in the younger age at onset group and of female patients in the older
      age at onset group. The most frequent heralding symptom was cognitive decline in
      the group with earlier onset and oropharyngeal dysfunction in the later-onset
      group. Seizures occurred only in the younger age at onset group. Chorea was not a
      presenting sign but developed later in the course of the disease and, with
      dystonia, was more prevalent in the early age at onset group, whereas rigidity
      and bradykinesia were more prevalent in the older age at onset group. Patients in
      both groups developed gait, cognitive, and behavioral disorders at some point
      during the course of the disease. Furthermore, a slow and steady decline in IQ
      was observed on serial neuropsychologic testing in patients from both groups.
      Imaging studies were normal early and most commonly revealed neostriatal atrophy
      later in the course of the disease. In this report, we describe the
      characteristics of 12 patients with childhood-onset Huntington disease and review
      those previously reported, expanding our knowledge about the features of
      childhood-onset Huntington disease, underlining the differences with patients
      with adult-onset Huntington disease, and suggesting a differential phenotype
      within patients with childhood-onset Huntington disease depending on the age at
      onset.

PMID- 16901425
TI  - Transient periventricular echodensities in preterms and neurodevelopmental
      outcome.
AB  - Little is known about the clinical evolution and neurologic sequelae of transient
      periventricular echodensities in the neonatal period. The aim of our study was to
      assess the neurodevelopmental outcome in preterm infants with transient
      periventricular echodensities. Cerebral ultrasonography was performed within the
      first 72 hours of life on all preterms with a < or = 37 weeks' gestational age
      who were admitted consecutively to the Neonatal Intensive Care Unit of the
      University of Parma from January 2001 to December 2002. Cerebral ultrasonography
      was performed at least twice within the 14th postnatal day and was repeated
      weekly until 40 weeks' postconceptional age. Transient aspecific echodensities
      were defined as areas in the periventricular region brighter than the choroid
      plexus persisting less than 14 days. One hundred sixty-four preterm infants were
      selected and divided into three groups: (1) 78 preterm infants without ultrasound
      abnormalities, (2) 50 preterm infants with transient periventricular
      echodensities, and (3) 36 preterm infants with persistent echodensities.
      Developmental outcome was assessed at 44 weeks' postconceptional age, after 1
      month from the discharge and at the corrected ages of 3, 6, 9, and 12 months
      using the Griffiths Mental Developmental Scale. Group 1 and 2 infants showed
      normal neurodevelopment in 88.5% and 94% of cases, respectively, whereas the
      preterm infants belonging to group 3 had a favorable outcome in 22.2% (P < .001)
      of cases only. In conclusion, our study demonstrates how infants with transient
      echodensities show a neurodevelopmental outcome that is entirely identical to
      infants with a steadily negative ultrasound finding.

PMID- 16901426
TI  - Expression of the N-methyl-D-aspartate receptor subunit R1 in the developing
      human hippocampus.
AB  - It has been suggested that the N-methyl-D-aspartate (NMDA) receptor family plays
      a key role in synaptic plasticity and synaptogenesis that is essential for
      memory, learning, differentiation, and development. Although gene expression of
      these receptors has been analyzed in the experimental animal brain and in some
      diseases of the adult or elderly human brain, it has not been studied in the
      developing human brain. Using in situ hybridization, we investigated the
      expression of the NMDAR1 gene in the hippocampi of 16 human neonates who were
      between 22 and 40 weeks of gestation and had no evidence of critical episodes of
      brain insult at autopsy. Signals for NMDAR1 were detected ubiquitously at all
      developmental stages. Dense hybridization signals were uniformly detected in the
      granular cells of the dentate gyrus in all specimens. Stronger signals were
      observed in the larger-type pyramidal cells in the CA2 and CA3 regions compared
      with the pattern seen in the CA1 region in the smaller-type pyramidal cells.
      These results suggest that the NMDAR1 gene is expressed at 22 weeks and possibly
      occurs earlier in neuronal cell bodies of the dentate gyrus and all CA fields of
      Ammon's horn and that the NMDAR plays an important role in constructing neuronal
      networks in developing human brains.

PMID- 16901427
TI  - Short- and long-latency contributions to reciprocal inhibition during various
      levels of muscle contraction of individuals with cerebral palsy.
AB  - Deficits in reciprocal inhibition likely contribute to excessive antagonist
      muscle cocontraction during voluntary movements of individuals with cerebral
      palsy. This study examined neural contributions to reciprocal inhibition of the
      soleus motoneurons of individuals with spastic, diplegic cerebral palsy and
      nondisabled individuals during various levels of voluntary tibialis anterior
      contraction. A condition-test H-reflex paradigm examined short- and long-latency
      contributions to reciprocal inhibition of soleus neural pools during changing
      levels of voluntary tibialis anterior contraction. Electrically induced short-
      and long-latency inhibition was similar between healthy, neurologically intact
      control subjects and subjects with cerebral palsy during rest. With increasing
      levels of tibialis anterior contraction, control subjects experienced increasing
      levels of soleus motoneuron inhibition, especially of long-latency inhibitory
      responses. In contrast, there was no evidence of modulation of short- or long
      latency inhibition with increasing levels of tibialis anterior contraction among
      subjects with cerebral palsy. Deficits in long-latency (presynaptic) inhibition
      appear to contribute prominently to voluntary movement impairment of individuals
      with cerebral palsy.

PMID- 16901428
TI  - "Just look," he said.
AB  - Five personal examples are given illustrating the general principle that one can
      see if one looks or, conversely, that one cannot see anything that one believes
      not to exist.

PMID- 16901429
TI  - Posterior reversible encephalopathy syndrome revealing acute post-streptococcal
      glomerulonephritis.
AB  - A case of acute encephalopathy with posterior corticosubcortical vasogenic edema
      on magnetic resonance imaging is reported. Angiography showed cerebral arterial
      vasospasm. A diagnosis of acute post-streptococcal glomerulonephritis was made 2
      days after admission. This report highlights the fact that acute post
      streptococcal glomerulonephritis can be revealed by a posterior reversible
      encephalopathy syndrome and that cerebral vasospasm can concur with vasogenic
      edema in this condition.

PMID- 16901430
TI  - Facioscapulohumeral muscular dystrophy can be a cause of isolated childhood
      cognitive dysfunction.
AB  - Facioscapulohumeral muscular dystrophy is one of the most prevalent muscular
      dystrophies in the world, resulting from the deletion of tandem repeats on
      chromosome 4q35. Extramuscular associations include sensorineural hearing loss,
      mental retardation, and epilepsy. These manifestations are commonly found in
      those with large deletions and early onset of weakness. A 26-year-old patient
      with a long-standing history of hearing loss, learning disabilities, and epilepsy
      presented with new-onset weakness and an elevated serum creatinine kinase level.
      Genetic testing confirmed sporadic facioscapulohumeral muscular dystrophy with a
      fragment length of 12 kilobases (normal > 35 kilobases). This unique presentation
      suggests that facioscapulohumeral muscular dystrophy should be considered in the
      differential diagnosis of children with cognitive impairment, seizures, and
      hearing loss.

PMID- 16901431
TI  - Point mutation tRNA(Ser(UCN)) in a child with hearing loss and myoclonus
      epilepsy.
AB  - We report on a family with a 12-year-old boy who suffered from a maternally
      inherited syndrome characterized by a combination of sensorineural hearing loss,
      myoclonus epilepsy, ataxia, severe psychomotor retardation, short stature, and
      diabetes mellitus. First, he showed a muscular hypotonia with hearing loss;
      later, he developed a myoclonus epilepsy, growth failure, and severe psychomotor
      retardation. At the age of 10 years, he developed diabetes mellitus. After
      initiation of combined ubiquinone and vitamin C treatment, we observed a
      progression in psychomotor development. Lactate and pyruvate levels in blood and
      cerebrospinal fluid were normal. No ragged red fibers or ultrastructural
      abnormalities were seen in a skeletal muscle biopsy. Biochemical assays of
      respiratory chain complex activities revealed decreased activity of complexes I
      and IV. By sequence analysis of mitochondrial DNA encoding transfer ribonucleic
      acids (RNAs), a homoplasmic T to C substitution at nucleotide position 7512 was
      found affecting a highly conserved base pair in the tRNA(ser(UCN)) acceptor stem.
      Asymptomatic family members of the maternal line were heteroplasmic for the
      mutation in blood samples. Analysis of mitochondrial DNA in patients with hearing
      loss and myoclonus epilepsy is recommended, even in the absence of laboratory
      findings. Therapeutically, ubiquinone and antioxidants can be beneficial.

PMID- 16901432
TI  - Case of Bartter syndrome presenting with hypokalemic periodic paralysis.
AB  - Hypokalemic periodic paralysis can occur secondarily to excessive potassium loss.
      Thyrotoxicosis, diuretic ingestions, hyperaldosteronism, barium poisoning,
      Gitelman syndrome, and Bartter syndrome are among the disorders causing secondary
      hypokalemic periodic paralysis. Clinical presentation of Bartter syndrome with
      hypokalemic periodic paralysis is rare. A 12-year-old boy was admitted to our
      hospital because of transient paralysis. He had been suffering from transient
      weakness attacks for 2 years and had had a total of 10 attacks, lasting 1 to 3
      days. He had growth retardation, polyuria, and polydipsia. Laboratory
      examinations revealed hypokalemic alkalosis, normomagnesemia, hypercalciuria, and
      hyperaldosteronism. The clinical and laboratory findings were in accordance with
      Bartter syndrome. He has been followed up for 6 months and has suffered no
      further paralytic attacks under indomethacin therapy. This case highlights the
      importance of blood pH measurement in patients with hypokalemic periodic
      paralysis; it might prevent misdiagnosis and mismanagement in such diseases.

PMID- 16901433
TI  - Nonconvulsive status epilepticus on electroencephalography in a case with
      subacute sclerosing panencephalitis.
AB  - Subacute sclerosing panencephalitis is a neurodegenerative disease with a poor
      prognosis. We report a case of a 5 1/2-year-old boy who had emotional lability,
      cognitive difficulties, and myoclonia after a mild closed head injury. The
      magnetic resonance image of the brain and computed tomographic scan of the head
      were normal. His electroencephalogram (EEG) showed continuous nonconvulsive
      status epilepticus activity, which could not be suppressed with intravenous
      diazepam. After treatment with phenytoin for 2 days, an EEG showed periodic high
      amplitude sharp-and-slow-wave complexes, which were also not suppressed with
      intravenous diazepam. Since the patient had measles at 5 months of age, subacute
      sclerosing panencephalitis was considered, and the diagnosis was confirmed by the
      presence of measles antibodies in cerebrospinal fluid.

PMID- 16901435
TI  - Devic Disease in a Child With Primary Sjogren Syndrome.

PMID- 16901434
TI  - 28TH ANNUAL CARRELL-KRUSEN SYMPOSIUM.

PMID- 16901436
TI  - Unusual Phenotypic Expression of an XLRS1 Mutation in X-Linked Juvenile
      Retinoschisis.
AB  - ABSTRACT X-linked juvenile retinoschisis is a rare progressive vitreoretinal
      degenerative process that appears in early childhood, results in decreased visual
      acuity and blindness (if severe), and is caused by various mutations within the
      XLRS1 gene at Xp22.2. We report an affected family of Western European ancestry
      with X-linked juvenile retinoschisis. The family was found to carry a 304C-->T
      substitution in exon 4 of the XLRS1 gene, resulting in an Arg102Trp amino acid
      substitution. Two of the four available clinical cases in this family were found
      to carry the mutation. All available mothers of affected males were found to be
      unaffected carriers of the mutation, a typical feature of X-linked diseases. Two
      new female carriers, sisters of affected males, were identified and counseled
      accordingly. Questionnaires on visual functioning were given to the affected
      family members to examine the psychologic and sociologic impact of X-linked
      juvenile retinoschisis, which documented an associated stigma even when affected
      with a "mild" phenotype. (J Child Neurol 2006;21:331-333; DOI
      10.2310/7010.2006.00085).

PMID- 16901437
TI  - Reply to Zesiewicz et al.

PMID- 16901438
TI  - Aicardi's Epilepsy in Children.

PMID- 16901439
TI  - SOUTHERN PEDIATRIC NEUROLOGY SOCIETY, Annual Meeting, March 18, 2006.

PMID- 16901440
TI  - Animal models of germinal matrix hemorrhage.
AB  - Germinal matrix hemorrhage refers to bleeding that arises from the subependymal
      (or periventricular) germinal region of the immature brain. Clinical studies have
      shown that infants who experience germinal matrix hemorrhage can develop
      hydrocephalus or suffer from long-term neurologic dysfunction, including cerebral
      palsy, seizures, and learning disabilities. Understanding the causative factors
      and the pathogenesis of subsequent brain damage is important if germinal matrix
      hemorrhage is to be prevented or treated. Appropriate animal models are necessary
      to achieve this understanding. A number of animal species, including mice, rats,
      rabbits, sheep, pigs, dogs, cats, and primates, have been used to model germinal
      matrix hemorrhage. This literature review critically evaluates the animal models
      of germinal matrix hemorrhage. Each model has its own advantages and
      disadvantages; no single model is suitable for the study of all aspects of brain
      damage.

PMID- 16901441
TI  - Adjunctive lamotrigine for refractory epilepsy in adolescents with mental
      retardation.
AB  - Epilepsy is a major comorbid condition in adolescents with mental retardation and
      is often characterized by multiple seizure types that are refractory to
      treatment. This study (n = 22) describes a subanalysis of data from a larger
      multicenter study of adjunctive lamotrigine therapy in patients with mental
      retardation and refractory epilepsy and focuses on the outcome measures of
      seizure reduction, safety and tolerability, and impact on behaviors in
      adolescents with mental retardation and refractory epilepsy. The study kept
      baseline antiepileptic drugs constant and titrated lamotrigine over 8 weeks to
      the target dose, followed by an 8-week maintenance phase and then a 12-week
      optimization phase during which all antiepileptic drugs and lamotrigine could be
      altered as clinically indicated. Sixty percent of subjects had a 50% decrease in
      seizures by the end of the maintenance phase and a mean 39% reduction in seizure
      frequency by the end of the maintenance phase (25% by end of study) compared with
      baseline. Global improvements were observed in most patients, with statistically
      significant improvements in the Aberrant Behavior Checklist and the Habilitative
      Improvement Scale, which is predictive of less need for supportive care in
      activities of daily living and thus enhanced potential for greater independence.
      Lamotrigine-associated improvements in behavior can be attributed to improved
      control of seizures, a reduction in concomitant antiepileptic drugs, and/or
      direct mood-stabilizing and behavior-enhancing properties independent of the
      antiseizure effects of the drug. The results of this study suggest that
      lamotrigine is an important treatment option in adolescents with mental
      retardation and comorbid epilepsy.

PMID- 16901442
TI  - Treatment of anticonvulsant hypersensitivity syndrome with intravenous
      immunoglobulins and corticosteroids.
AB  - Anticonvulsant hypersensitivity syndrome is a specific severe idiosyncratic
      reaction to the aromatic antiepileptic drugs. The most frequent presenting
      symptoms are fever and rash, lymphadenopathy owing to lymphoid hyperplasia,
      hepatitis, and interstitial nephritis. Severe skin reactions (Stevens-Johnson
      syndrome or toxic epidermal necrolysis) have also been reported. Early detection
      is crucial owing to the high mortality rate. Although withdrawal of the offending
      drug is critical, the optimal treatment approach remains controversial. Previous
      studies report a severe course and prolonged hospital stay for cutaneous drug
      related reactions, including referral to a burn center, skin debridement, and
      allograft skin coverage. The aim of the present report is to describe four
      adolescents with antiepileptic drug hypersensitivity syndrome who were treated
      with intravenous immunoglobulin and systemic corticosteroids. All recovered
      completely following an uncomplicated and relatively short course and
      hospitalization. Findings indicate that this regimen might be a promising
      treatment option in this patient population. Larger, controlled trials are needed
      to reach a definitive conclusion.

PMID- 16901443
TI  - Pediatric Epstein-Barr virus-associated encephalitis: 10-year review.
AB  - Many neurologic manifestations of Epstein-Barr virus (EBV) infection have been
      documented, including encephalitis, aseptic meningitis, transverse myelitis, and
      Guillain-Barre syndrome. These manifestations can occur alone or coincidentally
      with the clinical picture of infectious mononucleosis. Since 1994, The Hospital
      for Sick Children has maintained a prospective registry of all children admitted
      with acute encephalitis. This report summarizes all cases of Epstein-Barr virus
      associated encephalitis compiled from 1994 to 2003. Twenty-one (6%) of 216
      children, median age 13 years (range 3-17 years), in the Encephalitis Registry
      were identified as having evidence of Epstein-Barr virus infection. This evidence
      consisted of convincing Epstein-Barr virus serology and/or positive cerebrospinal
      fluid polymerase chain reaction (PCR). One patient had symptoms of classic
      infectious mononucleosis; all others had a nonspecific prodrome, including fever
      (n = 17; 81%) and headache (n = 14; 66%). Slightly less than half (n = 10; 48%)
      had seizures and often had electroencephalograms showing a slow background (n =
      12; 57%). Many demonstrated cerebrospinal fluid pleocytosis (n = 17; 81%), and
      71% (n = 15) had abnormal magnetic resonance imaging findings. Two patients died,
      2 suffered mild deficits, and 16 were neurologically normal at follow-up. Most
      patients with Epstein-Barr virus encephalitis do not show typical symptoms of
      infectious mononucleosis. Establishing a diagnosis of Epstein-Barr virus
      encephalitis can be difficult, and, consequently, a combination of serologic and
      molecular techniques should be used when investigating a child with acute
      encephalitis. Most children make full recoveries, but residual neurologic
      sequelae and even death can and do occur.

PMID- 16901444
TI  - Differentiating autistic children with quantitative encephalography: a 3-month
      longitudinal study.
AB  - The present study used a single-channel quantitative electroencephalographic
      (EEG) assessment to differentiate autistic children from normal control subjects.
      One hundred five normal and 17 autistic children participated in the study. In
      addition to amplitude measures of the frequency bands of delta, theta, alpha,
      sensorimotor rhythm, and beta and the theta to beta ratio, intra- (6 minutes) and
      intersessional (3 months) consistencies were also examined. The results indicated
      that autistic children showed significantly higher quantitative EEG amplitudes in
      many of the frequency bands than normal children; furthermore, their quantitative
      EEG activities were found to be relatively unstable within a 6-minute session
      compared with normal children. Discriminant function analyses revealed that
      absolute sensorimotor rhythm and beta amplitudes were the best predictors that
      correctly differentiated autistic children from normal children in the present
      sample, with a high accuracy rate of 95.2%. In addition, quantitative EEG
      measurements of normal and autistic children were found to be generally
      consistent across the 3-month period.

PMID- 16901445
TI  - Congenital muscular dystrophy in Arab children.
AB  - The congenital muscular dystrophies are autosomal recessive disorders with
      different clinical phenotypes, the spectrum of which varies between different
      ethnic communities. We report our findings in 21 Arab children with congenital
      muscular dystrophy. All 21 cases were of the pure type, with normal mental
      status, except 1 case with perinatal hypoxic-ischemic insult. Fourteen were
      laminin alpha2 (merosin) deficient, and six were laminin alpha2 positive; laminin
      alpha2 status was not determined in one patient. None of the laminin alpha2
      deficient patients achieved independent ambulation, whereas three of the laminin
      alpha2-positive patients were able to walk. The elevated levels of serum creatine
      kinase did not differentiate the two groups and tended to decrease after the age
      of 5 years. Radiologic evaluation demonstrated an abnormal central white-matter
      signal in 11 of 13 laminin alpha2-deficient and in 1 of 5 laminin alpha2-positive
      patients; none had evidence of brain dysplasia. Nerve conduction velocities were
      normal in 5 of 5 laminin alpha2-positive patients, whereas in the laminin alpha2
      deficient patients, it was slow in 9 of 11 for the motor nerves and normal in 8
      of 9 for the sensory nerve. Two of the laminin alpha2-positive patients had
      pseudohypertrophy of the calves, and two of the laminin alpha2-deficient ones had
      seizures. The patient in whom the laminin alpha2 status was not determined had a
      severe course, an abnormal central white-matter signal, and epilepsy and
      resembled more the laminin alpha2-deficient group.

PMID- 16901446
TI  - Corpus callosum size and neuropsychologic impairment in adolescents who were born
      preterm.
AB  - Prematurity is associated with cerebral abnormalities that might account for
      poorer cognitive performance. The aim of our study was to investigate the
      correlations between corpus callosum reductions and neuropsychologic performance
      in adolescents who were born preterm. Twenty-five subjects born before 33 weeks'
      gestation were compared with 25 subjects born at term and of similar age, gender,
      and sociocultural status. All subjects underwent magnetic resonance imaging and
      neuropsychologic examinations. Premature subjects performed worse than controls
      in global cognitive functioning, verbal memory, and verbal fluency. Corpus
      callosum measurements showed a global reduction owing mainly to thinning in the
      splenium, posterior midbody, and genu. Corpus callosum size significantly
      correlated with gestational age, Wechsler Performance IQ, and memory performance.
      These results suggest that cerebral growth during infancy does not compensate for
      corpus callosum reduction and that this reduction reflects neuropsychologic
      deficit. The cognitive impairment can arise from the paucity of the complex
      interneuronal connections owing to fiber damage, particularly myelinated fibers.

PMID- 16901447
TI  - Bone mineral status in pediatric outpatients on antiepileptic drug monotherapy.
AB  - Drug-induced osteopenia has been reported in institutionalized children on
      chronic antiepileptic drug therapy. The aim of this study was to assess
      longitudinally bone mineral status in pediatric outpatients on antiepileptic drug
      monotherapy. The study group consisted of 30 ambulatory children on a normal
      diet: 15 on valproic acid, 11 on carbamazepine, and 4 on phenobarbital
      monotherapy. Bone mineral density, serum active vitamin D (1,25-dihydroxyvitamin
      D), and certain biochemical markers of bone formation (calcium, phosphorus,
      alkaline phosphatase, intact parathyroid hormone, osteocalcin, calcitonin, and
      urinary calcium to serum creatinine and urinary phosphorus to serum creatinine
      ratios) were studied at the beginning of antiepileptic drug monotherapy and at
      the end of 2 years of treatment. Age- and sex-specific Z-scores of bone mineral
      density were measured at anterior-posterior L2-L4 by dual-energy x-ray
      absorptiometry. Drug-induced osteopenia was defined in only two patients (one on
      carbamazepine and the other on phenobarbital monotherapy), with Z-scores of bone
      mineral density less than -1.5. Serum levels of active vitamin D and biochemical
      markers were not significantly correlated with the Z-scores of bone mineral
      density. We detected a frequency of antiepileptic drug-induced osteopenia of 6.7%
      in pediatric outpatients after 2 years of monotherapy. However, osteopenia was
      not attributed to a defect in serum active vitamin D production owing to
      hyperparathyroidism in children on antiepileptic drug monotherapy.

PMID- 16901448
TI  - Temporal trends in the incidence and case fatality of stroke in children and
      adolescents.
AB  - A recent study reported that mortality from stroke in children and adolescents
      decreased by 58% from 1979 to 1998, although it wasn't clear if the case fatality
      or the incidence of stroke in this age group is decreasing. We report trends of
      stroke incidence and case fatality in children and adolescents within a large
      biracial population. The study involved collection of all strokes in the study
      population between January 1, 1988 and December 31, 1989, July 1, 1993 and June
      30, 1994, and January 1, 1999 and December 31, 1999, at all of the regional
      hospitals serving the Greater Cincinnati/Northern Kentucky population (only the
      children's hospital in 1988). Study nurses reviewed the medical records of all
      inpatients with stroke-related discharge diagnoses and abstracted relevant data.
      A study physician reviewed each abstract to determine whether a stroke or
      transient ischemic attack had occurred. A total of 54 strokes occurred in
      children or adolescents younger than 20 years during the three study periods (30%
      African American, 70% Caucasian, and 56% female). The overall incidence rate of
      all strokes in children younger than 15 years was 6.4/100,000 in 1999, a
      nonsignificant increase when compared to 1988. The 30-day case-fatality rates
      were 18% in 1988-1989, 9% in 1993-1994, and 9% in 1999. We found that the
      incidence of strokes in children has been stable over the past 10 years. The
      previously reported nationwide decrease in overall stroke mortality in children
      might be due to decreasing case fatality after stroke and not decreasing stroke
      incidence. Based on our data, we conservatively estimated that approximately 3000
      children less than 20 years old would have a stroke in the United States in 2004.

PMID- 16901449
TI  - Leukoencephalopathy with bilateral anterior temporal lobe cysts.
AB  - Recently, several reports describing patients with a nonprogressive clinical
      course, increased signal in the cerebral white matter, and cystic changes in the
      anterior temporal lobes on magnetic resonance imaging (MRI) have appeared. To
      date, 25 patients with this very distinctive condition have been described. We
      report four new cases of this newly recognized entity. All have been identified
      primarily because of the distinctive MRI features consisting of the very unusual
      anterior temporal lobe cystic changes. The clinical features are characterized by
      severe, disabling, but nonprogressive mental and motor retardation. Magnetic
      resonance spectroscopy has shown increased myo-inositol and decreased N
      acetylaspartate in the cerebral white matter. This is a distinctive, probably
      genetic, condition with characteristic neuroimaging and clinical features. In the
      appropriate clinical situation, the neuroimaging features are diagnostic.

PMID- 16901450
TI  - Meningismus is a commonly overlooked finding in tension-type headache in children
      and adolescents.
AB  - At present, both migraine and tension-type headaches in children are believed to
      be chronic primary headaches. Meningeal signs in both cases are ignored or not
      examined, and the neurologic status is considered normal. This is the first study
      that focuses on meningeal signs in children with chronic headaches. The study
      population comprised 1738 patients aged 5 to 17 years who were examined in an
      outpatient neurologic clinic over a 6-year period. Particular attention was paid
      to examination of meningeal signs, including nuchal rigidity, Kernig's sign,
      Brudzinski's three signs (upper, middle, and lower), the "tripod" sign, and
      Guillain's and facial signs; the presence of these signs was regarded as
      meningismus syndrome. Some meningeal signs were found in 12% of 1007 children
      suffering from migraine, whereas 97% of 731 children with tension-type headaches
      had the whole set of meningeal signs. This suggested that meningismus is the
      major clinical syndrome in chronic tension-type headaches in children and
      adolescents. Chronic mild sterile (possibly autoimmune) inflammation of meninges
      (dura mater) can be caused by a preceding infection, as well as minor trauma of
      the head and/or back. Prolonged rest in a recumbent position usually resulted in
      relief or complete disappearance of both headache and meningeal signs. Monitoring
      of the meningeal signs is helpful for evaluation of the patient's condition in
      the course of treatment.

PMID- 16901451
TI  - Coincidence of semilobar holoprosencephaly and Chiari II malformation:
      correlation of prenatal diagnostics and neuropathologic findings.
AB  - As holoprosencephaly and Chiari II malformation differ considerably, both in
      pathogenesis and in phenotypic localization, the coincidence of both entities is
      extremely rare. The case presented is, to our knowledge, the first published
      report comprising a combination of a semilobar holoprosencephaly associated with
      a Chiari II malformation and a myelomeningocele diagnosed prenatally and
      confirmed by postmortem neuropathologic evaluation. These findings indicate that
      in the case of pre- and postnatal detection of a myelomeningocele and/or Chiari
      II malformation, possible additional intracranial malformation, such as a
      semilobar holoprosencephaly, should also be taken into account and vice versa.

PMID- 16901452
TI  - Metronidazole: newly recognized cause of autonomic neuropathy.
AB  - Metronidazole is a commonly used antibiotic prescribed for the treatment of
      anaerobic and protozoal infections of the gastrointestinal and genitourinary
      tracts. It is associated with numerous neurologic complications, including
      peripheral neuropathy. Neuropathy is typically detected in patients on chronic
      therapy, although it has been documented in those taking large doses for acute
      infections. Numerous case reports have been published describing motor and
      sensory neuropathy, yet autonomic neuropathy has not been described with
      metronidazole use. A previously healthy 15-year-old girl presented with
      complaints of burning pain in her feet following a short course of metronidazole
      for vaginitis. She could obtain pain relief only by submerging her feet in ice
      water. Examination revealed cold and swollen lower extremities that became
      erythematous and very warm when removed from the ice water. Temperature
      perception was reduced to the upper third of the shin bilaterally. Deep tendon
      reflexes and strength were preserved. Nerve conduction studies demonstrated a
      peripheral neuropathy manifested by reduced sensory nerve and compound muscle
      action potentials. Reproducible sympathetic skin potential responses could not be
      obtained in the hand and foot, providing evidence of a concurrent autonomic
      neuropathy. A thorough evaluation revealed no other cause for her condition.
      Repeated nerve conduction studies and sympathetic skin potentials returned to
      normal over the course of 6 months, paralleling the patient's clinical
      improvement. Metronidazole is a potential cause of reversible autonomic
      neuropathy.

PMID- 16901453
TI  - Case of X-linked myopathy with excessive autophagy.
AB  - We report a 12-year-old boy with a vacuolar myopathy with clinical and histologic
      features of X-linked myopathy with excessive autophagy. This is a rare and slowly
      progressive disease of skeletal muscle without cardiac, nervous system, or other
      organ involvement. The differential diagnosis of vacuolar myopathy includes acid
      maltase deficiency, Danon disease, and X-linked myopathy with excessive
      autophagy.

PMID- 16901454
TI  - Second malignant neoplasms following the treatment of brain tumors in children.
AB  - We investigated retrospectively 992 children with central nervous system tumors
      who were treated at our center between 1970 and 2004. All of the patients were
      treated by surgery, chemotherapy, and/or radiotherapy. Six patients developed
      second malignant neoplasms, and their clinical and histopathologic
      characteristics are reviewed in this article. The second malignant neoplasms were
      diagnosed as non-Hodgkin lymphoma, myelodysplastic syndrome, basal cell
      carcinoma, malignant melanoma, Kaposi sarcoma, and high-grade neuroectodermal
      tumor. The initial diagnoses were ependymoblastoma in one, medulloblastoma in
      three, and low-grade astrocytoma in two patients. The median latency time was
      3.03 years (range 0.39-22.93 years). The outcome varied according to the
      histopathologic type of the second tumor. The patients who developed non-Hodgkin
      lymphoma and myelodysplastic syndrome died of progressive disease. The patients
      with second skin neoplasms are alive as of the time of this writing. The patient
      with Kaposi sarcoma developed one of the rare reported second malignant neoplasms
      following a primary brain tumor in childhood. A wide spectrum of second malignant
      neoplasms was detected after treatment of primary brain tumors with surgery,
      radiotherapy, and chemotherapy. Long-term follow-up is therefore necessary for
      the child who has survived a primary central nervous system tumor.

PMID- 16901456
TI  - Electrokinetic fingerprinting of grafted polyelectrolyte layers--a theoretical
      approach.
AB  - Electrokinetic fingerprinting (EF) was introduced by Marlow and Rowell [Marlow
      BJ, Rowel RL. Langmuir 1990;6:1088] for the comprehensive characterization of
      charged particle surfaces. Afterwards, EF was applied by many groups for the
      characterization of "hard" (i.e. non-swelling) surfaces. However, the advantages
      of EF could not yet utilized for the characterization of grafted polyelectrolyte
      layers (PL) since the theoretical background was not yet elaborated. A theory for
      the characterization of PL at complete dissociation of the functional groups was
      developed by Ohshima [Adv Colloid Interface Sci 1995;62:189] and later extended
      by Dukhin et al. [Dukhin S, Zimmermann R, Werner C. J Colloid Interface Sci
      2005;286:761] for any degree of dissociation. Further progress in the
      characterization of soft surfaces may be achieved by combining EF and surface
      conductivity (SC) measurements. Both theory and experiment demonstrate that
      integrated measurements of SC and apparent zeta potential zeta(a) in broad ranges
      of pH and ionic strength provide information about Donnan potential Psi(D),
      surface charge, pK and surface potential Psi(0), while the interpretation is more
      uncertain, when only zeta(a) is measured. This advanced method of PL
      characterization is established for PL grafted on flat surfaces. When PL are
      formed on spherical particles, the SC may be measured by means of conductometry
      and/or dielectric spectroscopy. However, the current theories can only be applied
      within a rather narrow range of the practically relevant conditions. To overcome
      this limitation, an unified approach to the theory of electrophoresis for
      spherical particles with grafted PL was elaborated taking into account the
      existence of two different electrokinetic models for soft surfaces. While one
      model is focused on hydrodynamic permeability of soft surface and disregards
      surface current, another model considers the surface current and disregards
      electrokinetic water transport within the soft surface layer. Unification became
      possible through generalization of the capillary osmosis theory over soft
      surfaces.

PMID- 16901455
TI  - Reconciling diabetes management and the ketogenic diet in a child with pyruvate
      dehydrogenase deficiency.
AB  - A 4-year-old girl with pyruvate dehydrogenase deficiency, static encephalopathy,
      and seizure disorder treated with the ketogenic diet presented in severe diabetic
      ketoacidosis. Pyruvate dehydrogenase deficiency is a rare genetic defect of
      mitochondrial energy metabolism that leads to inefficient glucose use and lactic
      acidosis. The ketogenic diet provides the brain with an alternate fuel source,
      but its implementation opposes traditional diabetes management. Faced with this
      therapeutic dilemma, we aimed to maintain ketosis without compromising safety to
      optimize neurologic function and quality of life. This is the first report, to
      our knowledge, of a child simultaneously treated with the ketogenic diet and
      exogenous insulin. A 28-month follow-up revealed excellent glycemic control,
      improved activity level, significant developmental achievements, and, perhaps
      most striking, catch-up linear growth from < 5th percentile to the 50th
      percentile. Her progress to date indicates that diabetes does not preclude use of
      the ketogenic diet.

PMID- 16901457
TI  - Stable free radicals in insect cuticles: electron spin resonance spectroscopy
      reveals differences between melanization and sclerotization.
AB  - Insect cuticles (exuviae; cast skins) were examined for the first time by ESR
      spectroscopy for the presence of stable free radicals, as found in melanins. All
      cuticles, except those from a locust albino strain, irrespective of the presence
      of melanin, provided single-line signals of varied g-values and linewidths. The
      ESR signals of melanins, isolated or in cuticles, were characterized by g-values
      <2.004 and small linewidths in the range of 4-6G, while sclerotized cuticles,
      lacking melanin, showed g-values >2.004 and broad linewidths of 5-11 G. The
      melanin spectra were comparable to those reported for eumelanins with indol-based
      monomers. Minor signals ascribed to pheomelanins were found in several probes.
      The 'sclerotin' spectra were broader and displayed unresolved hyperfine structure
      in some cases. As for melanins, the location and environment of the radicals in
      cuticles giving rise to the two types of ESR spectra could not be assigned.
      Changes in the radical environment due to insecticide or solvent treatment can be
      detected by ESR spectroscopy.

PMID- 16901458
TI  - Premolar and molar rotation in wild Japanese serow populations on Honshu Island,
      Japan.
AB  - The skulls of 1195 Japanese serow (Capricornis crispus) from six geographically
      distinct populations were examined for tooth rotation. Our objectives were to
      determine tooth rotation patterns in Japanese serows, investigate geographical
      variation in tooth rotation and examine whether space limitations in the jaw
      accounted for variations. We then sought to explain the origin of tooth rotation
      in the Japanese serow. Rotated teeth were found in 131 specimens (62 males, 57
      females and 12 unknown gender), with no statistically significant difference
      between males and females (chi(2)=0.03, P=0.86, d.f.=1). Among the six
      populations, the frequency of tooth rotation varied from 3.7-32.1% (average
      11.0%). Most tooth rotation occurred in the upper third and fourth premolars. The
      lingual cusp of anomalous teeth was rotated 30 degrees -90 degrees mesially or
      distally from the buccolingual tooth axis, and the rotation direction differed
      among populations. However, we found no difference in skull or tooth morphology
      between normal individuals and those with tooth rotation. Therefore, hereditary
      factors may be involved in Japanese serow tooth rotation. We concluded that
      genetic differentiation occurred in the past among local Japanese serow
      populations isolated in mountainous habitats. Gene frequencies were likely
      subject to random drift, especially during possible population bottlenecks, when
      genetic factors could most strongly affect the direction of rotation.

PMID- 16901459
TI  - Understanding disorders of the masticatory system.

PMID- 16901461
TI  - Sphingolipids and the formation of sterol-enriched ordered membrane domains.
AB  - This review is focused on the formation of lateral domains in model bilayer
      membranes, with an emphasis on sphingolipids and their interaction with
      cholesterol. Sphingolipids in general show a preference for partitioning into
      ordered domains. One of the roles of cholesterol is apparently to modulate the
      fluidity of the sphingolipid domains and also to help segregate the domains for
      functional purposes. Cholesterol shows a preference for sphingomyelin over
      phosphatidylcholine with corresponding acyl chains. The interaction of
      cholesterol with different sphingolipids is largely dependent on the molecular
      properties of the particular sphingolipid in question. Small head group size
      clearly has a destabilizing effect on sphingolipid/cholesterol interaction, as
      exemplified by studies with ceramide and ceramide phosphoethanolamine. Ceramides
      actually displace sterol from ordered domains formed with saturated
      phosphatidylcholine or sphingomyelin. The N-linked acyl chain is known to be an
      important stabilizer of the sphingolipid/cholesterol interaction. However, N-acyl
      phosphatidylethanolamines failed to interact favorably with cholesterol and to
      form cholesterol-enriched lateral domains in bilayer membranes.
      Glycosphingolipids also form ordered domains in membranes but do not show a
      strong preference for interacting with cholesterol. It is clear from the studies
      reviewed here that small changes in the structure of sphingolipids alter their
      partitioning between lateral domains substantially.

PMID- 16901460
TI  - Oral fluid proteolytic effects on histatin 5 structure and function.
AB  - Histatins are human salivary antifungal proteins that are prone to extensive
      enzymatic degradation upon their release into the oral cavity. Histatin
      proteolysis, leading to the disappearance of the intact protein can be expected
      to have functional consequences. Histatin 5, comprising 24 residues, is the
      smallest of the major salivary histatins and the most active in terms of its
      antifungal properties. The rate and mode of histatin 5 degradation were
      determined by incubating the protein in whole saliva supernatant for various time
      intervals. Fragmentation products were collected by reversed-phase high
      performance liquid chromatography (RP-HPLC), characterised structurally by matrix
      assisted laser desorption/ionisation-time of flight (MALDI-TOF) mass spectrometry
      and functionally in a fungal growth inhibition assay. Of the 19 fragments
      identified, 16 were derived from single proteolytic cleavage events in histatin
      5. A remarkable finding was the inter-subject consistency in the histatin 5
      degradation pattern. Added histatin 5 disappeared from whole saliva supernatant
      at an average rate of 105+/-22 microg/ml/h, which in part could explain the
      virtual absence of histatin 5 in whole saliva. Despite the rapid proteolysis of
      histatin 5, the early degradation mixture was as active in antifungal assays as
      intact histatin 5. These data demonstrate that the oral-fluid mediated
      proteolysis of histatin 5 represents an intrinsic biological property of whole
      saliva. The data also reveal that the early proteolysis phase of histatin 5 does
      not abolish the antifungal properties associated with this protein.

PMID- 16901462
TI  - Grafting of polylysine with polyethylenoxide prevents demixing of O
      pyromellitylgramicidin in lipid membranes.
AB  - Both natural and synthetic polycations can induce demixing of negatively charged
      components in artificial and possibly in natural membranes. This process can
      result in formation of clusters (binding of several components to a polycation
      chain) and/or domains (aggregation of clusters and formation of a separate phase
      enriched in some particular component). In order to distinguish between these two
      phenomena, a model lipid membrane system containing ion channels, formed by a
      negatively charged peptide, O-pyromellitylgramicidin, and polycations of
      different structures was used. Microelectrophoresis of liposomes, changes in
      boundary potential of planar bilayers, the shape of compression curves and
      potentials of lipid and lipid/peptide monolayers were used to monitor the
      electrostatic factors in polymer adsorption to the membrane and peptide-polymer
      interactions. The synthesized PEO-grafted polylysine, PLL-PEO20000, did not
      induce peptide demixing monitored by stabilization of the gramicidin channels, in
      contrast to parent polylysine (PLL). Both polymers were shown to bind effectively
      to negatively charged liposomes and lipid monolayers, suggesting that the
      ineffectiveness of PLL-PEO20000 was not due to reduction of its binding. It was
      hypothesized that PLL-PEO20000 could not induce domain formation due to steric
      hindrance of long PEO chains preventing lateral fusion of clusters. Another
      copolymer, PLL-PEO4000, having four PEO chains of 4000 Da, exhibited intermediate
      effect between PLL and PLL-PEO20000, which shows the importance of the copolymer
      architecture for the effect on the lateral distribution of OPg channels. The
      model system can be relevant to regulation of lateral organization of ion
      channels and other components in natural membrane systems.

PMID- 16901463
TI  - Resveratrol regulates the expression of LXR-alpha in human macrophages.
AB  - The naturally occurring polyphenol resveratrol has been associated with the
      beneficial effects of red wine consumption on cardiovascular disease and shown to
      inhibit atherosclerosis in animal models. To determine if resveratrol affects the
      expression of genes that control lipid homeostasis in human macrophages, we
      measured expression changes in the LXR-alpha pathway, crucial to cholesterol
      efflux, and in genes that mediate lipoprotein uptake. Resveratrol treatment of
      THP-1 macrophages induced LXR-alpha at mRNA and protein levels. Increased
      recruitment of RNA polymerase II to the LXR-alpha promoter suggested that up
      regulation was at least partly mediated by transcriptional mechanisms.
      Resveratrol also induced LXR-alpha in human monocyte-derived macrophages together
      with elevated ABCA1 and ABCG1 mRNA levels. Moreover, resveratrol repressed the
      expression of the lipid uptake genes LPL and SR-AII. The ability of resveratrol
      to modulate expression of the genes involved in lipid uptake and efflux suggests
      that polyphenols can potentially limit cholesterol accumulation in human
      macrophages.

PMID- 16901464
TI  - Heterotypic cell interactions on a dually patterned surface.
AB  - It is worth investigating heterotypic cell-cell interactions by mimicking their
      in vivo structures and environment. In the present study, physiological cellular
      response and behavior of hepatocytes and endothelial cells were investigated by
      controlling their contact periphery in a new co-culture system. Rat primary
      hepatocytes and bovine endothelial cells were co-cultured on a dually patterned
      surface. Hepatic physiological functions such as albumin secretion and ammonium
      metabolism were enhanced by increasing heterotypic cell-cell interactions in a
      patterned co-culture. Furthermore, enhanced hepatic functions through heterotypic
      interactions are effective within a limited area apart from endothelial cells as
      evidenced by immunofluorescence staining of hepatic intracellular albumin,
      indicating that heterotypic interactions act in a paracrine manner. Thus,
      heterotypic cell communications that play indispensable roles in increasing
      hepatic physiological functions should be obtained with an increasing periphery
      of two-cell domains. These findings are important for the reconstruction of
      complex tissues such as liver and pancreas.

PMID- 16901465
TI  - Hexamerization by the N-terminal domain and intersubunit phosphorylation by the C
      terminal domain of cyanobacterial circadian clock protein KaiC.
AB  - Cyanobacterial clock protein KaiC has a hexagonal, pot-shaped structure composed
      of six identical dumbbell-shaped subunits. The opposing spherical regions of the
      dumbbell-shaped structures correspond to the N-terminal and C-terminal domains of
      KaiC. Previously, we hypothesized that the N-terminal domain of KaiC is
      responsible for the ATP-induced hexamerization of KaiC while the C-terminal
      domain is responsible for the phosphorylation of KaiC (Hayashi et al. 2004, J.
      Biol. Chem. 279, 52331-52337). Here, we tested that hypothesis using the purified
      protein of each domain. We prepared N-terminal and C-terminal domain proteins
      (KaiCN and KaiCC, respectively), examined their function by analyzing their ATP-
      or 5'-adenylylimidodiphosphate (AMPPNP; an unhydrolyzable ATP analog)-induced
      hexamerization, interactions with KaiA, and phosphorylation, and we demonstrated
      the following: (1) KaiCN had higher ATP- or AMPPNP-induced oligomerization
      activity than KaiCC. (2) KaiCc had phosphorylation activity as KaiCWT whereas
      KaiCN had no activity. (3) KaiCC interacted with KaiA whereas KaiCN did not. (4)
      The interactions of KaiCC with KaiA did not require that KaiC has a hexamer
      structure. (5) The interactions of KaiCC with KaiA enhanced the phosphorylation
      of KaiCC. Furthermore, we presented evidence for the intersubunit phosphorylation
      of KaiC. KaiCCatE2-, which lacks KaiC phosphorylation activity due to mutations
      of the catalytic Glu residues, was phosphorylated when it was co-incubated with
      KaiCC. We propose that the KaiC hexamer consists of a rigid ring structure formed
      by six N-terminal domains with hexamerization activity and a flexible structure
      formed by six C-terminal domains with intersubunit phosphorylation activity.

PMID- 16901466
TI  - Amine free crystal structure: the crystal structure of d(CGCGCG)2 and methylamine
      complex crystal.
AB  - We succeeded in the crystallization of d(CGCGCG)2 and methylamine Complex. The
      crystal was clear and of sufficient size to collect the X-ray crystallographic
      data up to 1.0 A resolution using synchrotron radiation. As a result of X-ray
      crystallographic analysis of 2Fo-Fc map was much clear and easily traced. It is
      the first time monoamine co-crystallizes with d(CGCGCG)2. However, methylamine
      was not found from the complex crystal of d(CGCGCG)2 and methylamine. Five Mg
      ions were found around d(CGCGCG)2 molecules. These Mg ions neutralized the anion
      of 10 values of the phosphate group of DNA with five Mg2+. DNA stabilized only by
      a metallic ion and there is no example of analyzing the X-ray crystal structure
      like this. Mg ion stabilizes the conformation of Z-DNA. To use monoamine for
      crystallization of DNA, we found that we can get only d(CGCGCG)2 and Mg cation
      crystal. Only Mg cation can stabilize the conformation of Z-DNA. The method of
      using the monoamine for the crystallization of DNA can be applied to the
      crystallization of DNA of long chain of length in the future like this.

PMID- 16901467
TI  - Activity-dependent shedding of heparin-binding EGF-like growth factor in brain
      neurons.
AB  - Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is initially
      produced as a membrane-anchored precursor (pro-HB-EGF) and subsequently liberated
      from the cell membrane through ectodomain shedding. Here, we characterized the
      molecular regulation of pro-HB-EGF shedding in the central nervous system.
      Cultured neocortical or hippocampal neurons were transfected with the alkaline
      phosphatase-tagged pro-HB-EGF gene and stimulated with various neurotransmitters.
      Both kainate and N-methyl-D-aspartate, but not agonists for metabotropic
      glutamate receptors, promoted pro-HB-EGF shedding and HB-EGF release, which were
      attenuated by an exocytosis blocker and metalloproteinase inhibitors. In the
      brain of transgenic mice over-expressing human pro-HB-EGF, kainate-induced
      seizure activity decreased content of pro-HB-EGF-like immunoreactivity and
      conversely increased levels of soluble HB-EGF. There was concomitant
      phosphorylation of EGF receptors (ErbB1) following seizures, suggesting that
      seizure activities liberated HB-EGF and activated neighboring ErbB1 receptors.
      Therefore, we propose that glutamatergic neurotransmission in the central nervous
      system plays a crucial role in regulating ectodomain shedding of pro-HB-EGF.

PMID- 16901468
TI  - Recent clinical failures in Parkinson's disease with apoptosis inhibitors
      underline the need for a paradigm shift in drug discovery for neurodegenerative
      diseases.
AB  - Understanding the mechanisms of neuronal death in concert with the identification
      of drugable molecular targets key to this process has held great promise for the
      development of novel chemical entities (NCEs) to halt neurodegenerative disease
      progression. Two key targets involved in the apoptotic process identified over
      the past decade include the mixed lineage kinase (MLK) family and glyceraldehyde
      phosphate dehydrogenase (GAPDH). Two NCEs, CEP-1347 and TCH346, directed against
      these respective targets have progressed to the clinic. For each, robust
      neuroprotective activity was demonstrated in multiple in vitro and in vivo models
      of neuronal cell death, but neither NCE proved effective Parkinson's disease (PD)
      patients. These recent clinical failures require a reassessment of both the
      relevance of apoptosis to neurodegenerative disease etiology and the available
      animal models used to prioritize NCEs for advancement to the clinic in this area.

PMID- 16901469
TI  - Multiple effects of sentential constraint on word processing.
AB  - Behavioral and electrophysiological studies have uncovered different patterns of
      constraint effects on the processing of words in sentences. Whereas response time
      measures have indicated a reduced scope of facilitation from strongly
      constraining contexts, event-related brain potential (ERP) measures have instead
      revealed enhanced facilitation for semantically related endings in such
      sentences. Given this disparity, and the concomitant possibility of functionally
      separable stages of context effects, the current study jointly examined
      expectancy (cloze probability) and constraint effects on the ERP response to
      words. Expected and unexpected (but plausible) words completed strongly and
      weakly constraining sentences; unexpected items were matched for contextual fit
      across the two levels of constraint and were semantically unrelated to the most
      expected endings. N400 amplitudes were graded by expectancy but unaffected by
      constraint and seemed to index the benefit of contextual information. However, a
      later effect, in the form of increased frontal positivity from 500 to 900 ms post
      stimulus-onset, indicated a possible cost associated with the processing of
      unexpected words in strongly constraining contexts.

PMID- 16901470
TI  - Modality matters: the effects of stimulus modality on the 4- to 30-Hz brain
      electric oscillations during a lexical decision task.
AB  - The aim of the current study was to assess modality-specific brain oscillatory
      responses during cognitive processing. Brain oscillatory ERD/ERS responses of the
      4- to 30-Hz EEG frequency bands were examined during lexical decision where the
      task is to identify whether the presented stimulus is a word or a pseudoword.
      Seven subjects performed the task with visual stimuli and twelve subjects with
      auditory stimuli. Visual stimuli elicited greater theta ERS responses as compared
      to the auditory stimuli. Both stimulus modalities elicited alpha and beta
      frequency ERD, these being greater for the auditory stimuli. Auditory stimuli
      elicited also later emerging beta ERS responses, absent for the visual stimuli.
      The lexicality effects (words vs. pseudowords) were greater for the auditory than
      for the visual stimuli. When studying brain oscillatory correlates of cognitive
      processing, the stimulus modality matters. Some effects may arise and some vanish
      depending on in which modality a cognitive experiment is being conducted.

PMID- 16901471
TI  - Apoptosis mediated by p53 in rat neural AF5 cells following treatment with
      hydrogen peroxide and staurosporine.
AB  - AF5 neural cells derived from fetal rat mesencephalic tissue were immortalized
      with a truncated SV40 LT vector lacking the p53-inactivating domain to maintain
      long-term cultures with a p53-responsive phenotype. This study examined p53
      function in producing programmed cell death in propagating AF5 neural cells after
      exposure to hydrogen peroxide (H2O2) and the kinase inhibitor staurosporine
      (STSP). Concentration-dependent exposure of AF5 cells to 0-800 mM H2O2 and STSP
      at 0-1000 nM revealed increasing cytotoxicity from MTS cell viability assays.
      Apoptosis occurred at 400 mM H2O2 as evidenced by subG1 DNA and Annexin V flow
      cytometry analyses and cellular immunofluorescence staining with propidium
      iodide, anti-Annexin V and DAPI. DNA fragmentation, caspase-3/7 activity and
      cytochrome c release into cytosol also confirmed H2O2-mediated apoptotic events.
      p53 protein levels were increased over 24 h by H2O2 in a coordinated fashion with
      mdm2 expression. p53 activation by H2O2 was evidenced by elevated Ser15
      phosphorylation, increased luciferase p53 reporter activity and upregulation of
      the downstream p53 targets p21(waf1) and apoptotic proteins, bax, Noxa and PUMA.
      STSP exposure produced apoptosis demonstrated by DNA fragmentation, caspase-3/7
      activity, cytochrome c release and over 24 h was accompanied by sustained
      increase in p53 and Ser15 phosphorylation, rise in p21(waf1) and bax and a
      transient increase in p53 reporter activity but without Annexin V binding. These
      findings demonstrate that AF5 cells undergo apoptosis in response to H2O2
      mediated oxidative stress and signal pathway disruption by STSP that therefore
      would be useful in studies related to p53-dependent neuronal cell death and
      neurodegeneration.

PMID- 16901472
TI  - Central heme oxygenase-carbon monoxide pathway participates in the
      lipopolysaccharide-induced tolerance in rats.
AB  - Recently, heme oxygenase-carbon monoxide (HO-CO) pathway has been reported to be
      involved in the development of lipopolysaccharide (LPS) fever. However, no
      information exists about its participation in LPS tolerance, which is defined by
      an attenuation of the febrile response to repeated administrations of LPS. Thus,
      we tested the hypothesis that HO-CO pathway plays a role in endotoxin tolerance,
      which was induced by means of three consecutive LPS intraperitoneal injections
      (i.p.) at 24-h intervals. Body temperature (Tb) was measured by biotelemetry.
      Induction of the HO pathway using intracerebroventricular (i.c.v.) heme lysinate
      reversed tolerance, and this effect could be prevented by pretreatment with ODQ
      [a soluble guanylate cyclase (sGC) inhibitor; i.c.v.]. These results indicate
      that HO-CO pathway seems to be down-regulated during LPS tolerance, and that CO
      is the HO product that can prevent LPS tolerance, acting via cGMP. In further
      support, either biliverdine or iron (the others HO products; i.c.v.) had no
      effect in LPS-induced tolerance.

PMID- 16901473
TI  - Expression of prokineticin receptors in mouse cultured astrocytes and involvement
      in cell proliferation.
AB  - Effects of prokineticins (PKs), a novel family of bioactive peptides with a
      mitogenic action to endothelial cells of the endocrine gland and testis, on
      astrocytic functions were examined. Mouse cultured astrocytes expressed PK-R1
      type PK receptors, while there was little expression of the PK-R2 type. PKs
      caused increases in astrocytic cytosolic Ca2+ levels and BrdU incorporation.
      Increases in Ca2+ levels by PK-2 were diminished by U73122 (a phospholipase C
      inhibitor). PK-induced BrdU incorporation was inhibited by U73122, GF109203 (a
      protein kinase C inhibitor) and PD98059 (a MEK/ERK inhibitor). These results
      indicate that PK receptors are expressed in astrocytes and regulate astrocytic
      proliferation.

PMID- 16901474
TI  - Progesterone binding to the tryptophan residues of human alpha1-acid
      glycoprotein.
AB  - Binding studies between progesterone and alpha1-acid glycoprotein allowed us to
      demonstrate that the binding site of progesterone contains one hydrophobic
      tryptophan residue and that the structure of the protein is not altered upon
      binding. The data obtained at saturated concentrations of progesterone clearly
      reveal the type of interaction at physiological levels.

PMID- 16901475
TI  - Essential role of Rho/ROCK-dependent processes and actin dynamics in mediating
      leptin-induced hypertrophy in rat neonatal ventricular myocytes.
AB  - BACKGROUND: Obesity is associated with increased leptin production, which may
      contribute to cardiac hypertrophy. Although leptin has been shown to produce
      cardiomyocyte hypertrophy, its mechanism of action is far from clear. Rho
      proteins have been suggested as major contributors to cardiac hypertrophy,
      although their potential role in mediating the effect of leptin has not been
      studied. METHODS: We determined the role of Rho and Rho-associated kinase (ROCK)
      as mediators of leptin-induced cell hypertrophy in cultured neonatal rat
      ventricular myocytes. RESULTS: Leptin (3.1 nmol/L) significantly increased cell
      surface area by 32+/-5% and leucine incorporation by 43 +/- 7%. These effects
      were associated with significant activation of RhoA to 450 +/- 40% of pre-leptin
      levels that was attenuated by pretreatment with an anti-leptin receptor (anti
      OBR) antibody (166 ng/mL) to 120 +/- 20% of control values. Both the RhoA
      inhibitor C3 exoenzyme and ROCK inhibitor Y-27632 potently attenuated leptin
      induced increased cell surface area and leucine incorporation. The hypertrophic
      effect of leptin was associated with an increase in phosphorylation of the actin
      binding protein cofilin to 290 +/- 20% of control values. In addition, the
      increase in polymerization of actin, as reflected by a decrease in the G/F-actin
      ratio, was significantly inhibited by both the anti-OBR antibody and Y-27632.
      Leptin-induced hypertrophy was also attenuated by disruption of actin filaments
      with 50 nmol/L latrunculin B. RhoA pathway inhibitors and latrunculin B also both
      attenuated leptin-induced ERK1/2 and p38 activation. CONCLUSION: Our results
      indicate that the activation of Rho and actin dynamics play a pivotal role in
      leptin signaling leading to the development of cardiomyocyte hypertrophy.

PMID- 16901476
TI  - MAPK activation and apoptotic alterations in hearts subjected to calcium paradox
      are attenuated by taurine.
AB  - OBJECTIVE: The Ca2+ -paradox is an important phenomenon to study cell injury
      induced by Ca2+ -overload in myocardium. Although intracellular Ca2+ -overload
      acts as a trigger and modulator of cell death due to apoptosis under various
      pathophysiological conditions, the presence of apoptosis in hearts subjected to
      Ca2+ -paradox has not been demonstrated. Since taurine attenuates the changes in
      cardiac function due to Ca2+ -paradox, this study investigated the occurrence and
      mechanisms of apoptosis in Ca2+ -paradoxic hearts treated in the absence and
      presence of taurine. METHODS: Ca2+ -paradox was induced by perfusing the isolated
      rat heart with Ca2+ -free medium for 5 min followed by reperfusion with Ca2+ 
      containing medium for 30 min. Apoptosis related signal transduction mechanisms
      were determined in Ca2+ -paradoxic hearts perfused with or without 10 mM taurine.
      RESULTS: Marked alterations in cardiac function and the presence of apoptosis
      were seen in Ca2+ -paradoxic hearts reperfused for 30 min. Unlike the total
      protein contents in hearts subjected to Ca2+ -paradox, the contents of
      phosphorylated p38 mitogen-activated protein kinase (MAPK), extracellular signal
      regulated kinase (ERK)1, ERK2 and c-jun amino-terminal kinase were increased by
      125 +/- 8.6%, 296 +/- 14.3%, 213 +/- 8.5% and 133 +/- 4.2%, respectively vs.
      control. Caspase-3 and phosphorylated Bcl-2 contents were also increased by 193
      +/- 10.2% and 134 +/- 5.0% vs. control whereas phosphorylated Bad and the ratio
      of Bcl-2/Bad were depressed by 32 +/- 10.8% and 0.23 +/- 0.5% vs. control in Ca2+
      -paradoxic hearts. The apoptosis as seen in Ca2+ -paradoxic hearts reperfused for
      30 min was not evident in hearts at 10 min Ca2+ -repletion but was similar to
      hearts subjected to 60 min Ca2+ -repletion. These changes in the apoptotic
      pathway in cardiomyocytes subjected to Ca2+ -paradox were prevented by taurine.
      Furthermore, taurine attenuated the KCl- or ATP-induced increase in intracellular
      concentration of Ca2+ in cardiomyocytes. CONCLUSIONS: This study suggests that
      cardiac dysfunction due to Ca2+ -paradox may be associated with apoptosis. In
      addition, the beneficial effects of taurine on cardiac function may be related to
      the attenuation of changes in MAPK and apoptotic signal transduction mechanisms
      in Ca2+ -paradoxic hearts.

PMID- 16901478
TI  - Analytical evaluation of a new immunonephelometric method for homocysteine
      measurement.
AB  - BACKGROUND AND OBJECTIVES: Increased plasma homocysteine, a sulphur amino acid
      closely related to methionine metabolism, is considered an independent risk
      factor for cardiovascular diseases. Over the last years, the request to clinical
      laboratories for homocysteine measurement is constantly increased and, for this
      reason, several new methods have been developed, mainly with the aim of using
      them on completely automated instruments for routine analyses. In this paper, we
      evaluated a new immunonephelometric method for homocysteine determination on the
      Dade Behring BNII nephelometer. METHODS: Linearity, recovery, limit of detection
      (LOD) and total imprecision and were assessed; moreover, the method was compared
      with a HPLC reference method and with an automated immunoassay method (AxSYM
      Abbott). RESULTS: Recovery range was 96.4-104.2%, LOD was 0.5 micromol/L and
      total imprecision ranged from 5.0% to 7.6%. For the comparison study, the
      immunonephelometric method showed a good correlation both with HPLC (Y=1.02X
      0.79, R(2)=0.99) and with the AxSYM method (Y=1.003X+0.06, R(2)=0.98). The Bland
      Altman plot analysis shows that the immunonephelometric method has a slight
      positive bias with both HPLC (mean: 1.03 micromol/L, 95% confidence interval:
      0.28-1.79 micromol/L) and AxSYM methods (mean: 0.45 micromol/L, 95% confidence
      interval: -0.03-0.94 micromol/L). CONCLUSION: The new nephelometric method from
      Dade Behring, for its analytical performance, can be easily considered a suitable
      method for homocysteine routine measurement; moreover, it cannot be ruled out
      that the widespread availability of nephelometers in clinical laboratories play a
      leading role in the choice of this method.

PMID- 16901477
TI  - Ischemic postconditioning protects remodeled myocardium via the PI3K-PKB/Akt
      reperfusion injury salvage kinase pathway.
AB  - OBJECTIVE: We tested whether ischemic postconditioning (IPostC) is protective in
      remodeled myocardium. METHODS: Post-myocardial infarct (MI)-remodeled hearts
      after permanent coronary artery ligation and one kidney one clip (1K1C)
      hypertensive hearts of male Wistar rats were exposed to 40 min of ischemia
      followed by 90 min of reperfusion. IPostC was induced by six cycles of 10 s
      reperfusion interspersed by 10 s of no-flow ischemia. Activation of reperfusion
      injury salvage kinases was measured using Western blotting and in vitro kinase
      activity assays. RESULTS: IPostC prevented myocardial damage in both MI-remodeled
      and 1K1C hearts, as measured by decreased infarct size and lactate dehydrogenase
      release, and improved function. The reduction in infarct size and the recovery of
      left ventricular contractility achieved by IPostC was less in 1K1C hearts, but
      was unchanged in MI-remodeled hearts when compared to healthy hearts. In
      contrast, the recovery of inotropy was unaffected in 1K1C hearts, but was less in
      MI-remodeled hearts. Inhibition of the phosphatidylinositol 3-kinase (PI3K)
      pathway with LY294002 abolished the protective effects of IPostC on both disease
      models and healthy hearts. Western blot analysis in conjunction with in vitro
      kinase activity assays identified protein kinase B (PKB)/Akt but not p42/p44
      extracellular-signal regulated kinase 1/2 (ERK1/2) as the predominant kinase in
      IPostC-mediated cardioprotection in remodeled hearts. IPostC increased
      phosphorylation of the PKB/Akt downstream targets eNOS, GSK3beta, and p70S6K in
      remodeled hearts. CONCLUSION: Our results offer evidence that IPostC mediates
      cardioprotection in the remodeled rat myocardium primarily via activation of the
      PI3K-PKB/Akt reperfusion injury salvage kinase pathway.

PMID- 16901479
TI  - Optimisation and parallelisation strategies for Monte Carlo simulation of HIV
      infection.
AB  - In recent years, the study of immune response behaviour through mathematical and
      computational models has attracted considerable efforts. The dynamics of key cell
      types, and their interactions, has been a primary focus in terms of building a
      picture of how the immune system responds to a threat. Discrete methods, based on
      lattice Monte-Carlo (MC) models, with their flexibility and relative simplicity
      have previously been used to model the immune system behaviour. However, due to
      speed and memory constraints, large-scale simulations cannot be done on a single
      computer. Key issues in the reduction of simulation time are code optimisation
      and code parallelisation. In this paper, optimisation and parallelisation
      solutions are discussed, with reference to existing MC simulation code for
      dynamics of HIV infection.

PMID- 16901480
TI  - A novel mode of tangential migration of cortical projection neurons.
AB  - Projection neurons of the developing cerebral cortex are generated in the
      cerebral ventricular zone and subsequently move to the developing cortical plate
      via radial migration. Conversely, most inhibitory interneurons originate in the
      ganglionic eminences and enter the developing cortical plate by tangential
      migration. Using immunohistochemical analysis together with tracer labeling
      experiments in organotypic brain slices, we show that a portion of cortical
      projection neurons migrates tangentially over long distances. Lineage analysis
      revealed that these neurons are derived from Emx1+ cortical progenitors and
      express the transcription factor Satb2 but do not express GABA or Olig1. In vitro
      and in vivo analysis of reeler mutant brains demonstrated that although reeler
      mutation does not influence tangential migration of interneurons, it affects the
      tangential migration of cortical projection neurons.

PMID- 16901481
TI  - Influence of external and intracellular pH on propofol-induced responses in rat
      locus coeruleus neurons.
AB  - The effect of external and intracellular pH on propofol-induced responses in rat
      locus coeruleus neurons was examined using intracellular recording from in vitro
      brain slice preparations. Experimental variation of external pH from 7.34 to 6.81
      did not affect the propofol-induced responses. In contrast, raising the external
      pH from 7.34 to 8.10 resulted in enhanced 100 microM propofol effects. The
      effects were 1.8 times greater on membrane hyperpolarization (pH 8.10: 11.8 +/-
      1.3 mV; pH 7.34: 6.5 +/- 1.0 mV, n = 5) and 1.5 times greater on reduction in
      input resistance (pH 8.10: 38.2 +/- 6.3%; pH 7.34: 24.7 +/- 4.1%, n = 5).
      Cytosolic acidification was used in which 1/3 NaCl in artificial cerebrospinal
      fluid was replaced with weak organic acids--sodium acetate. It did not
      significantly affect the propofol-induced responses. On the other hand,
      intracellular alkalinization with 5 mM NH(4)Cl markedly suppressed the 100 microM
      propofol-induced membrane hyperpolarization (1.0 +/- 0.6 mV; control: 13.9 +/-
      0.9 mV, n = 5) and reduction of input resistance (38.1 +/- 1.3%; control: 61.0 +/
      4.3%, n = 5). However, the presence of 3-5 mM ammonium acetate also showed the
      similarly suppressing effect on membrane hyperpolarization (1.7 +/- 0.6 mV;
      control: 9.2 +/- 1.8 mV, n = 5) and reduction of input resistance (28.5 +/- 8.5%;
      control: 37.0 +/- 6.3%, n = 5) caused by 100 microM propofol. We suggested that
      the main suppressing effect of NH(4)Cl results from ammonium ion, but not
      intracellular alkalinization. Furthermore, we examined the feature of
      pharmacological regulation of propofol-induced responses by pentobarbital or
      alphaxalone during pH changes. It appears that neither pentobarbital nor
      alphaxalone could allosterically modulate the propofol-induced responses, which
      had been affected by pH changes.

PMID- 16901482
TI  - Calponin binds G-actin and F-actin with similar affinity.
AB  - Calponins are actin-binding proteins that are implicated in the regulation of
      actomyosin. Calponin binds filamentous actin (F-actin) through two distinct sites
      ABS1 and ABS2, with an affinity in the low micromolar range. We report that
      smooth muscle calponin binds monomeric actin with a similar affinity (K(d) of
      0.15 microM). We show that the arrangement of binding is similar to that of F
      actin by a number of criteria, most notably that the distance between Cys273 on
      calponin and Cys374 of actin is 29A when measured by fluorescent resonance energy
      transfer, the same distance as previously reported for F-actin.

PMID- 16901483
TI  - New insights on the use of desipramine as an inhibitor for acid ceramidase.
AB  - Treatment of different cancer cell lines with desipramine induced a time- and
      dose-dependent downregulation of acid ceramidase. Desipramine's effect on acid
      ceramidase appeared specific for amphiphilic agents (desipramine, chlorpromazine,
      and chloroquine) but not other lysomotropic agents such as ammonium chloride and
      bafilomycin A1, and was not transcriptionally regulated. The cathepsin B/L
      inhibitor, CA074ME, but not the cathepsin D inhibitor, pepstatin A, blocked
      desipramine's effect on acid ceramidase. Desipramine led to a more pronounced
      downregulation of sphingosine compared to ceramide suggesting acid ceramidase
      inhibition is important to desipramine's mechanism of action. This study reveals
      a new mechanism of action for desipramine.

PMID- 16901484
TI  - Normalization of hyperinsulinemia by chronic opioid receptor blockade in
      hyperandrogenemic women.
AB  - OBJECTIVE: Evaluation of the effects of naltrexone on hyperinsulinemia and
      hyperandrogenemia in hyperandrogenemic, hyperinsulinemic women. DESIGN:
      Controlled clinical study. SETTING: Department of Gynecologic Endocrinology and
      Reproductive Medicine, Center of Obstetrics and Gynecology, Medical University of
      Innsbruck, Austria. PATIENT(S): Thirty-nine hyperandrogenemic, hyperinsulinemic
      women were studied. INTERVENTION(S): Women were treated with naltrexone (50 mg/d)
      for >or=3 weeks. MAIN OUTCOME MEASURE(S): Body mass index (BMI), gonadotropin
      (LH, FSH) and androgen (T, free T, DHEAS) levels, and plasma levels of glucose,
      insulin, and C-peptide, during a standard 75-g oral glucose tolerance test
      (OGTT), were determined before and during chronic opiate receptor blockade.
      RESULT(S): The BMI did not change during therapy. When OGTT was repeated after
      treatment with naltrexone, glucose levels were not different from those before
      treatment. Insulin response, however, had dramatically declined. We also observed
      a significant decrease in the levels of serum androgens. CONCLUSION(S):
      Hyperinsulinemia associated with hyperandrogenemia can be improved or completely
      abolished by chronic opiate receptor blockade. This observation suggests that
      endogenous opiates play a critical role in the process leading to
      hyperinsulinemia in hyperandrogenemia.

PMID- 16901485
TI  - Stress sensitivity and the development of affective disorders.
AB  - Depressive disorders are the most common form of mental illness in America,
      affecting females twice as often as males. The great variability of symptoms and
      responses to therapeutic treatment emphasize the complex underlying neurobiology
      of disease onset and progression. Evidence from human and animal studies reveals
      a vital link between individual stress sensitivity and the predisposition toward
      mood disorders. While the stress response is essential for maintenance of
      homeostasis and survival, chronic stress and maladaptive responses to stress
      insults can lead to depression or other affective disorders. A key factor in the
      mediation of stress responsivity is the neuropeptide corticotropin-releasing
      factor (CRF). Studies in animal models of heightened stress sensitivity have
      illustrated the involvement of CRF downstream neurotransmitter targets, including
      serotonin and norepinephrine, in the profound neurocircuitry failure that may
      underlie maladaptive coping strategies. Stress sensitivity may also be a risk
      factor in affective disorder development susceptibility. As females show an
      increased stress response and recovery time compared to males, they may be at an
      increased vulnerability for disease. Therefore, examination of sex differences in
      CRF and downstream targets may aid in the elucidation of the underlying causes of
      the increased disease presentation in females. While we continue to make progress
      in our understanding of mood disorder etiology, we still have miles to go before
      we sleep. As an encouraging number of new animal models of altered stress
      sensitivity and negative stress coping strategies have been developed, the future
      looks extremely promising for the possibility of a new generation of drug targets
      to be developed.

PMID- 16901486
TI  - Acute distal biceps tendon rupture--a new surgical technique using a de
      tensioning suture to brachialis.
AB  - Acute distal biceps rupture is a devastating injury in the young athlete and
      surgical repair offers the only chance of a full recovery. We report a new
      surgical technique used in 14 cases of acute distal tendon rupture in which the
      'suture anchor technique' and a de-tensioning suture was employed. In this
      procedure the distal end of the biceps is re-attached to the radial tuberosity
      using a sliding whip stitch suture and the proximal part of the distal tendon
      repair attached to the underlying brachialis muscle with absorbable sutures. This
      restores correct anatomical alignment and isometric pull on the distal tendon and
      de-tensions the repair in the early post-operative period, allowing early
      rehabilitation and an early return to activity. In all cases patients regained a
      full pre-injury level of sporting activity at a mean period of 6.2 months (2-9
      months).

PMID- 16901488
TI  - A survey of role stress, coping and health in Australian and New Zealand hospital
      nurses.
AB  - BACKGROUND: Previous research has identified international and cultural
      differences in nurses' workplace stress and coping responses. We hypothesised an
      association between problem-focused coping and improved health, emotion-focused
      coping with reduced health, and more frequent workplace stress with reduced
      health. OBJECTIVES: Test the above hypotheses with Australian and New Zealand
      nurses, and compare Australian and New Zealand nurses' experience of workplace
      stress, coping and health status. PARTICIPANTS AND SETTINGS: Three hundred and
      twenty-eight New South Wales (NSW) and 190 New Zealand (NZ) volunteer acute care
      hospital nurses (response rate 41%) from randomly sampled nurses. DESIGN AND
      METHOD: Postal survey consisting of a demographic questionnaire, the Nursing
      Stress Scale, the WAYS of Coping Questionnaire and the SF-36 Health Survey
      Version 2. RESULTS: Consistent with hypotheses, more frequent workplace stress
      predicted lower physical and mental health. Problem-focused coping was associated
      with better mental health. Emotion-focused coping was associated with reduced
      mental health. Contrary to hypotheses, coping styles did not predict physical
      health. NSW and NZ scored effectively the same on sources of workplace stress,
      stress coping methods, and physical and mental health when controlling for
      relevant variables. CONCLUSIONS: Results suggest mental health benefits for
      nurses who use problem-solving to cope with stress by addressing the external
      source of the stress, rather than emotion-focused coping in which nurses try to
      control or manage their internal response to stress. Cultural similarities and
      similar hospital environments could account for equivalent findings for NSW and
      NZ.

PMID- 16901489
TI  - The effect of ethanol extract of Hypericum lysimachioides on lipid profile in
      hypercholesterolemic rabbits and its in vitro antioxidant activity.
AB  - Hypercholesterolemia, high cholesterol diet and oxidative stress increase serum
      total cholesterol and LDL cholesterol levels resulting in increased risk for
      development of atherosclerosis. Antioxidants play an important role in inhibiting
      and scavenging radicals, thus providing protection to humans against infectious
      and degenerative diseases. Literature shows that the antioxidant activity is high
      in medicinal plants. Realizing the fact that, this study was carried out to
      determine the effect of ethanol extract of Hypericum lysimachioides Boiss var
      lysimachioides (Guttifera) on serum lipid levels and serum lipid peroxidation in
      hypercholesterolemic rabbits. The rabbits were divided into four groups and these
      groups were fed with diets containing standard laboratory diet (Group I),
      standard laboratory diet and ethanol extracts of H. lysimachioides (HL) (50mg/kg
      body weight) (Group II), standard laboratory diet, ethanol extracts of HL
      (50mg/kg body weight) and cholesterol (100mg/kg body weight) (Group III), and
      finally standard laboratory diet and cholesterol (100mg/kg body weight) (Group
      IV), for 5 weeks. Feeding cholesterol increased serum cholesterol and LDL
      cholesterol levels significantly in Group IV as compared to the other groups.
      Ethanol extract of HL with high cholesterol diet significantly lowered LDL
      cholesterol and total cholesterol levels in the rabbits of Group III as compared
      to the Group IV. The level of serum triacylglycerol was found to be similar to
      all comparison groups. HDL cholesterol levels were also increased significantly
      in Groups II and III as compared to Group IV. Statistically significant
      difference was found in Group IV as compared to all other groups. The ethanol
      extract of HL with high cholesterol diet significantly lowered the serum MDA
      levels in the rabbits of Group III compared to the Group IV. The
      histopathological findings confirmed that the ethanol extract of HL restrained
      the progression of the hydropic degeneration and fatty changes in the liver and
      some atherosclerotic lesions in the aorta. The in vitro antioxidant activities of
      ethanol extract of HL was also evaluated. The free radical-scavenging properties
      of HL (IC(50)=28 microg/ml) were studied using 1,1-diphenyl-2-picrylhydrazyl
      (DPPH) assay system. Since plant phenolic compound is one of the phytochemicals
      possessing radical scavenging activity, the amount of total phenolic compound was
      also determined in ethanol extract of HL and total phenolic content of one
      milligram HL ethanol extract was equivalent to 307 microg of gallic acid. Total
      antioxidant activity of ethanol extract of HL was tested by using ferric
      thiocyanate (FTC) and thiobarbituric acid (TBA) methods. Antioxidative activities
      of ethanol extract of HL was found to be comparable with Vitamin E. In
      conclusion, the use of this extract could be useful in the management of
      cardiovascular disease in which atherosclerosis is important.

PMID- 16901490
TI  - Pioglitazone inhibits connective tissue growth factor expression in advanced
      atherosclerotic plaques in low-density lipoprotein receptor-deficient mice.
AB  - Connective tissue growth factor (CTGF) is expressed in atherosclerotic plaques.
      It is generally recognized that CTGF contributes to atherosclerosis by
      stimulating vascular smooth muscle cell (VSMC) proliferation and extracellular
      matrix production during the development of atherosclerosis. Recent studies
      indicate that CTGF may also contribute to plaque destabilization as it induces
      apoptosis and stimulates MMP-2 expression in VSMCs. Thiazolidinediones (TZDs), a
      new class of insulin sensitizing drugs for type 2 diabetes, inhibit
      atherosclerosis. However, their effect on CTGF expression in atherosclerotic
      plaques remains unknown. In this study, male LDL receptor-deficient mice were fed
      high-fat diet for 4 months to induce the formation of atherosclerotic plaques and
      then given the high-fat diet with or without pioglitazone for the next 3 months.
      At the end of the 7-month study, CTGF expression in aortic atherosclerotic
      lesions was examined. Results showed that CTGF expression was increased in mice
      fed the high-fat diet by seven-fold as compared to that in mice fed normal chow,
      but the treatment with pioglitazone significantly inhibited the high-fat diet
      induced CTGF expression. To verify these in vivo observations, in vitro studies
      using human aortic SMC were conducted. Quantitative real-time PCR and Western
      blot showed that pioglitazone inhibited TGF-beta-stimulated CTGF expression. In
      conclusion, the present study has demonstrated that pioglitazone inhibits CTGF
      expression in mouse advanced atherosclerotic plaques and in cultured human SMCs,
      and hence unveiled a possible mechanism potentially involved in the inhibition of
      atherosclerosis by TZD.

PMID- 16901491
TI  - A novel scratching approach for measuring age-related changes in the in situ
      toughness of bone.
AB  - A scratch test using a nanoindentation system was proposed in this study to
      assess the age-related changes in the in situ toughness of bone matrix at
      ultrastructural levels. A tissue removal energy density (u(r)) was defined and
      estimated as the work done by the scratch (U(T)) divided by the total volume of
      the scratch groove (u(s)). The value of u(s) was used as a relative measure of
      the in situ toughness of the tissue. Human cortical bone specimens obtained from
      middle-aged (between 49 and 59 years old) and elderly groups (over 69 years old)
      were tested using this technique. A significant difference in the estimated
      removal energy density (u(s)) in the secondary osteons was found between the
      middle-aged and elderly groups (5.49+/-0.696 vs. 4.09+/-1.30 N/mm(2),
      respectively).

PMID- 16901492
TI  - A generic detailed rigid-body lumbar spine model.
AB  - The objective of this work is to present a musculo-skeletal model of the lumbar
      spine, which can be shared and lends itself to investigation in many locations by
      different researchers. This has the potential for greater reproducibility and
      subsequent improvement of its quality from the combined effort of different
      research groups. The model is defined in a text-based, declarative, object
      oriented language in the AnyBody Modelling System software. Text-based models
      will facilitate sharing of the models between different research groups. The
      necessary data for the model has been taken from the literature. The work
      resulted in a detailed lumbar spine model with seven rigid segments with 18
      degrees-of-freedom and 154 muscles. The model is able to produce a maximum
      extension moment of 238 Nm around L5/S1. Moreover, a comparison was made with in
      vivo intradiscal pressure measurements of the L4-5 disc available from the
      literature. The model is based on inverse dynamics, where the redundancy problem
      is solved using optimization in order to compute the individual muscle forces and
      joint reactions. With the presented model it is possible to investigate a range
      of research questions, because the model is relatively easy to share and modify
      due to the use of a well-defined and self-contained scripting language.
      Validation is though still necessary for specific cases.

PMID- 16901493
TI  - Is economy of competitive cyclists affected by the anterior-posterior foot
      position on the pedal?
AB  - The primary purpose of this investigation was to test the hypothesis that cycling
      economy, as measured by rate of oxygen consumption (VO(2)) in healthy, young,
      competitive cyclists pedaling at a constant workrate, increases (i.e. VO(2)
      decreases) when the attachment point of the foot to the pedal is moved
      posteriorly on the foot. The VO(2) of 11 competitive cyclists (age 26.8+/-8.9
      years) was evaluated on three separate days with three anterior-posterior
      attachment points of the foot to the pedal (forward=traditional; rear=cleat
      halfway between the head of the first metatarsal and the posterior end of the
      calcaneous; and mid=halfway between the rear and forward positions) on each day.
      With a randomly selected foot position, VO(2) was measured as each cyclist
      pedaled at steady state with a cadence of 90 rpm and with a power output
      corresponding to approximately 90% of their ventilatory threshold (VT) (mean
      power output 203.3+/-20.8 W). After heart rate returned to baseline, VO(2) was
      measured again as the subject pedaled with a different anterior-posterior foot
      position, followed by another rest period and then VO(2) was measured at the
      final foot position. The key finding of this investigation was that VO(2) was not
      affected by the anterior-posterior foot position either for the group (p=0.311)
      or for any individual subject (p>or=0.156). The VO(2) for the group was 2705+/
      324, 2696+/-337, and 2747+/-297 ml/min for the forward, mid, and rear foot
      positions, respectively. The practical implication of these findings is that
      adjusting the anterior-posterior foot position on the pedal does not affect
      cycling economy in competitive cyclists pedaling at a steady-state power output
      eliciting approximately 90% of VT.

PMID- 16901494
TI  - Isolation of polymerase chain reaction-ready bacterial DNA from Lake Baikal
      sediments by carboxyl-functionalised magnetic polymer microspheres.
AB  - Carboxyl group-containing magnetic nonporous poly(2-hydroxyethyl methacrylate-co
      ethylene dimethacrylate) (P(HEMA-co-EDMA)) microspheres were used for the
      isolation of polymerase chain reaction (PCR)-ready DNA from samples of Baikal
      sediments. DNA was isolated using the phenol extraction method or the Soil DNA
      Isolation Kit. The occurrence of false-negative results in PCR caused by the
      presence of extracellular inhibitors in DNA samples was solved using solid phase
      reversible DNA immobilisation. PCR-ready DNA was reversibly adsorbed to the
      microspheres in the presence of 8.0% (w/v) poly(ethylene glycol) (PEG 6000) and
      2.0M sodium chloride concentrations. The adsorbed DNA was released from the
      microspheres in a low ionic strength TE buffer. The quality of isolated DNA was
      checked by PCR amplification.

PMID- 16901495
TI  - Development of septum-free injector for gas chromatography and its application to
      the samples with a high boiling point.
AB  - A novel apparatus with a simple structure has been developed for introducing
      samples into the vaporizing chamber of a gas chromatograph. It requires no septum
      due to the gas sealing structure over the carrier gas supply line. The septum
      free injector made it possible to use injection port temperatures as high as 450
      degrees C. Repetitive injection of samples with boiling points below 300 degrees
      C resulted in peak areas with relative standard deviations between 1.25 and 3.28%
      (n=5) and good linearity (r(2)>0.9942) for the calibration curve. In the analysis
      of polycyclic aromatic hydrocarbons and a base oil, the peak areas of components
      with high boiling points increased as the injection port temperature was
      increased to 450 degrees C.

PMID- 16901496
TI  - Development of a reversed-phase high-performance liquid chromatography method for
      the analysis of components from a closed-loop insulin delivery system.
AB  - A reversed-phase HPLC method has been developed which enables separation of the
      three components of a closed-loop insulin delivery system, namely concanavalin A
      methacrylamide (Con A-MA), dextran methacrylate (Dex-MA) and bovine insulin. The
      analysis of Con A-MA represents a significant challenge due to the formation of
      multiple conformations on contact with the chromatographic surface and the mobile
      phase. The extent of conformational change is shown to be dependent on a number
      of parameters: column temperature, mobile phase pH, contact time with the
      chromatographic surface, salt type and concentration and the organic modifier. By
      manipulation of these variables, protein denaturation can be minimised and
      recovery improved.

PMID- 16901497
TI  - Removal of copper on composite sewage sludge/industrial sludge-based adsorbents:
      the role of surface chemistry.
AB  - Sewage sludge and industrial waste oil sludge were pyrolyzed in an inert
      atmosphere at 650 or 950 degrees C, either as single components or as 50:50
      mixtures. Composite materials were used as adsorbents of copper ions from aqueous
      solution. The capacity for copper removal was comparable to that of commercial
      activated carbon. To relate the performance of materials to their properties, the
      surface features were characterized using adsorption of nitrogen, thermal
      analysis, XRF, potentiometric titration, and elemental analysis. The results
      indicated that a high copper removal capacity could be linked to basic surface pH
      and specific compounds present on the surface. The high removal ability of
      materials obtained at 650 degrees C is attributed to cation exchange reactions
      between calcium and magnesium in aluminosilicates, formed on their surface during
      heat treatment, and copper. On the other hand, the high degree of mineralization
      of the surface of the materials obtained at 950 degrees C promotes copper
      complexation and its surface precipitation as hydroxides or hydroxylcarbonate
      entities.

PMID- 16901498
TI  - Stable oxide nanoparticle clusters obtained by complexation.
AB  - We report on the electrostatic complexation between polyelectrolyte-neutral
      copolymers and oppositely charged 6-nm crystalline nanoparticles. For two
      different dispersions of oxide nanoparticles, the electrostatic complexation
      gives rise to the formation of stable nanoparticle clusters in the range 20-100
      nm. It is found that inside the clusters, the particles are "pasted" together by
      the polyelectrolyte blocks adsorbed on their surface. Cryo-transmission
      electronic microscopy allows visualization of the clusters and determination of
      the probability distribution functions in size and in aggregation number. The
      comparison between light scattering and cryo-microscopy results suggests the
      existence of a polymer brush around the clusters.

PMID- 16901499
TI  - Immobilization of Keggin and Preyssler tungsten heteropolyacids on various
      functionalized silica.
AB  - The Keggin and Preyssler tungsten heteropolyacids, H3PW12O40 and H15P5W30O110,
      have been immobilized on the inner surface of mesoporous MCM-41, fume silica and
      silica-gel by means of chemical bonding to aminosilane groups. The materials were
      characterized by FT-IR spectroscopy, low-angle XRD and BET surface area analysis.
      The tendencies of heteropolyacids adsorption in solution on functionalized
      silicas have been investigated by UV-vis. Among the functionalized silica
      materials, MCM-41 showed the largest amine to silica and the least heteropolyacid
      to silica ratios. The BET surface area revealed that in all three cases the
      surface area decreased after grafting amine group and anchoring of the HPAs
      clusters. Low-angle XRD analysis showed that by introducing HPA into
      functionalized MCM-41 the intensity of the main reflection decreased
      significantly.

PMID- 16901500
TI  - Rapid specific amplification of rat antibody cDNA from nine hybridomas in the
      presence of myeloma light chains.
AB  - Most monoclonal antibodies to mouse antigens have been derived from rat spleen
      mouse myeloma fusions. Many resultant hybridomas express one of several myeloma
      kappa chain transcripts, even though the parent myeloma may have been ascribed as
      not expressing light chain protein. Previous reports have only differentiated
      against one of these mouse light chains. We have found at least three different
      myeloma kappa transcripts in the panel of nine hybridomas that were derived from
      four different myeloma parents. We have designed an amplification strategy that
      differentiates the rearranged rat kappa chain from all mouse light chains.
      Moreover, this method is expedient as it requires minimal downstream
      manipulation.

PMID- 16901501
TI  - Alterations in contractile protein composition and function in human atrial
      dilatation and atrial fibrillation.
AB  - The cellular mechanisms responsible for contractile dysfunction associated with
      atrial fibrillation (AF) are still poorly understood. Atrial fibrillation is
      often preceded by atrial dilatation. This study aimed to explain contractile
      alterations associated with AF and their relation to atrial dilatation, by
      studying the relationships between atrial dimensions, contractile protein
      composition, force production and Ca(2+)-sensitivity. Force development was
      determined in mechanically isolated single skinned cardiomyocytes from right
      atrial appendages from patients with sinus rhythm without (SR;n=9), or with
      atrial dilation (SR+AD;n=11) or atrial fibrillation (AF;n=16). Echocardiography
      showed that, compared to the SR group, mean right atrial dimensions were
      increased by 18% and 35% in the SR+AD and AF group, respectively (P<0.05).
      Protein composition was determined by 1- and 2-dimensional gel electrophoresis.
      Compared to the SR group, the AF group exhibited: a reduction in the kinetics of
      force redevelopment (K(tr)) in isolated atrial cardiomyocytes, enhanced protein
      expression of the slow myosin heavy chain isoform (beta-MHC), an increase in
      troponin T (TnT) phosphorylation and a marked increase (70%) of the cytoskeletal
      protein desmin. Significant correlations were observed between the right atrial
      major axis (RA(major)) and beta-MHC expression as well as the desmin/actin ratio.
      Our findings indicate that dilatation may influence cardiomyocyte stability
      through altered desmin expression, but that it does not predispose to the
      alterations in contractile function observed in AF.

PMID- 16901502
TI  - Remodeled cardiac calcium channels.
AB  - Cardiac calcium channels play a pivotal role in the proper functioning of cardiac
      cells. In response to various pathologic stimuli, they become remodeled, changing
      how they function, as they adapt to their new environment. Specific features of
      remodeled channels depend upon the particular disease state. This review will
      summarize what is known about remodeled cardiac calcium channels in three disease
      states: hypertrophy, heart failure and atrial fibrillation. In addition, it will
      review the recent advances made in our understanding of the function of the
      various molecular building blocks that contribute to the proper functioning of
      the cardiac calcium channel.

PMID- 16901503
TI  - Crystal structure of visfatin/pre-B cell colony-enhancing factor 1/nicotinamide
      phosphoribosyltransferase, free and in complex with the anti-cancer agent FK-866.
AB  - Visfatin/pre-B cell colony-enhancing factor 1 (PBEF)/nicotinamide
      phosphoribosyltransferase (NAmPRTase) is a multifunctional protein having
      phosphoribosyltransferase, cytokine and adipokine activities. Originally isolated
      as a cytokine promoting the differentiation of B cell precursors, it was recently
      suggested to act as an insulin analog via the insulin receptor. Here, we describe
      the first crystal structure of visfatin in three different forms: apo and in
      complex with either nicotinamide mononucleotide (NMN) or the NAmPRTase inhibitor
      FK-866 which was developed as an anti-cancer agent, interferes with NAD
      biosynthesis, showing a particularly high specificity for NAmPRTase. The crystal
      structures of the complexes with either NMN or FK-866 show that the enzymatic
      active site of visfatin is optimized for nicotinamide binding and that the
      nicotinamide-binding site is important for inhibition by FK-866. Interestingly,
      visfatin mimics insulin signaling by binding to the insulin receptor with an
      affinity similar to that of insulin and does not share the binding site with
      insulin on the insulin receptor. To predict binding sites, the potential
      interaction patches of visfatin and the L1-CR-L2 domain of insulin receptor were
      generated and analyzed. Although the relationship between the insulin-mimetic
      property and the enzymatic function of visfatin has not been clearly established,
      our structures raise the intriguing possibility that the glucose metabolism and
      the NAD biosynthesis are linked by visfatin.

PMID- 16901504
TI  - Probing 3'-ssDNA loop formation in E. coli RecBCD/RecBC-DNA complexes using non
      natural DNA: a model for "Chi" recognition complexes.
AB  - The equilibrium binding of Escherichia coli RecBC and RecBCD helicases to duplex
      DNA ends containing varying lengths of polyethylene glycol (PEG) spacers within
      pre-formed 3'-single-stranded (ss) DNA ((dT)n) tails was studied. These studies
      were designed to test a previous proposal that the 3'-(dT)n tail can be looped
      out upon binding RecBC and RecBCD for 3'-ssDNA tails with n>or=6 nucleotides.
      Equilibrium binding of protein to unlabeled DNA substrates with ends containing
      PEG-substituted 3'-ssDNA tails was examined by competition with a Cy3-labeled
      reference DNA which undergoes a Cy3 fluorescence enhancement upon protein
      binding. We find that the binding affinities of both RecBC and RecBCD for a DNA
      end are unaffected upon substituting PEG for the ssDNA between the sixth and the
      final two nucleotides of the 3'-(dT)n tail. However, placing PEG at the end of
      the 3'-(dT)n tail increases the binding affinities to their maximum values (i.e.
      the same as binding constants for RecBC or RecBCD to a DNA end with only a 3'
      (dT)6 tail). Equilibrium binding studies of a RecBC mutant containing a nuclease
      domain deletion, RecB(Deltanuc)C, suggest that looping of the 3'-tail (when
      n>or=6 nucleotides) occurs even in the absence of the RecB nuclease domain,
      although the nuclease domain stabilizes such loop formation. Computer modeling of
      the RecBCD-DNA complexes suggests that the loop in the 3'-ssDNA tail may form at
      the RecB/RecC interface. Based on these results we suggest a model for how a loop
      in the 3'-ssDNA tail might form upon encounter of a "Chi" recognition sequence
      during unwinding of DNA by the RecBCD helicase.

PMID- 16901505
TI  - Evidence for low-grade systemic proinflammatory activity in patients with
      posttraumatic stress disorder.
AB  - Posttraumatic stress disorder (PTSD) may increase cardiovascular risk but the
      psychophysiological mechanisms involved are elusive. We hypothesized that
      proinflammatory activity is elevated in patients with PTSD as diagnosed by the
      Clinician Administered PTSD Scale (CAPS) interview. Plasma levels of
      proinflammatory C-reactive protein (CRP), interleukin (IL)-1beta, IL-6, and tumor
      necrosis factor (TNF)-alpha, and of anti-inflammatory IL-4 and IL-10 were
      measured in 14 otherwise healthy PTSD patients and in 14 age- and gender-matched
      healthy non-PTSD controls. Levels of TNF-alpha (p=0.038; effect size Cohen's
      d=0.58) and of IL-1beta (p=0.075, d=0.68) were higher in patients than in
      controls. CRP (d=0.10), IL-6 (d=0.18), IL-4 (d=0.42), and IL-10 (d=0.37) were not
      significantly different between groups. Controlling for traditional
      cardiovascular risk factors, mood, and time since trauma revealed lower IL-4 in
      patients than in controls (p=0.029) and rendered group differences in TNF-alpha
      and IL-1beta insignificant. In all subjects, TNF-alpha correlated with total
      (frequency and intensity) PTSD symptom cluster of re-experiencing (r=0.49,
      p=0.008), avoidance (r=0.37, p=0.050), and hyperarousal (r=0.42, p=0.026), and
      with PTSD total symptom score (r=0.37, p=0.054). Controlling for time since
      trauma attenuated these associations. The correlation between IL-1beta and total
      avoidance symptoms (r=0.42, p=0.028) became insignificant when controlling for
      anxiety and depression. IL-4 correlated with total hyperarousal symptoms (r=
      0.38, p=0.047), and after controlling for systolic blood pressure and smoking
      status, with PTSD total symptom score (r=-0.41, p=0.035). PTSD patients showed a
      low-grade systemic proinflammatory state, which, moreover, was related to PTSD
      symptom levels suggesting one mechanism by which PTSD could contribute to
      atherosclerotic disease.

PMID- 16901506
TI  - Frontal lobe volumes in schizophrenia: effects of stage and duration of illness.
AB  - While the changes in the volume of the temporal lobe and its sub-regions over the
      course of illness have been studied in patients with schizophrenia, few studies
      have examined changes in the frontal lobe between the first episode and the
      chronic stage. In this study, we focussed on the effect of illness stage and
      duration of illness on the volume of frontal lobe regions, though we also
      examined several other regions to establish the specificity of any effects, if
      observed, in this region. We compared the volumes of brain regions among 34 first
      episode schizophrenia patients, 49 chronic schizophrenia patients, 18 healthy
      controls matched, on average, to the first-episode patients and 21 healthy
      controls matched, on average, to the chronic patients. Logarithmic regression
      analyses examined the relationships between the duration of illness and the brain
      regional volumes in the patient group. The results showed that chronic patients
      had smaller prefrontal cortical grey matter volumes, but larger premotor cortical
      and putamen volumes compared to first-episode patients and matched healthy
      controls. Although there were significant patient-by-control group interactions
      in the cerebellum and sensori-motor cortical grey matter volumes, these did not
      survive correction for multiple comparisons. There was a significant exponential
      relation between the duration of illness and the volumes of prefrontal cortex,
      parieto-occipital cortex grey matter, thalamus and putamen, suggesting that these
      regions are susceptible to change as the disorder persists. The enlargement of
      the premotor cortex and putamen are likely to be a result of antipsychotic
      medication.

PMID- 16901507
TI  - Sperm competition promotes the exploitation of rival ejaculates.
AB  - In many polyandrous species, the second male to mate with a female has
      fertilization priority. Strategic mechanisms generating this pattern tend to
      involve facultative increases in ejaculate size by informed males. Here we
      suggest a novel mechanism to generate second male precedence in internal
      fertilizers, based on the established fact that the female site of insemination
      is hostile to sperm, and that non-sperm components of the ejaculate frequently
      act to ameliorate these hostile conditions. We suggest that in species where
      female remating is frequent and rapid, second male sperm precedence may be due to
      the prior buffering of the female tract by previous males' ejaculates. In this
      scenario, second male costs are lower due to reduced sperm mortality and/or the
      redundancy of seminal fluid. Contrary to many classical predictions, second males
      may gain a paternity advantage despite investing less in an ejaculate.

PMID- 16901508
TI  - Artificial neural networks can learn to estimate extinction rates from molecular
      phylogenies.
AB  - Molecular phylogenies typically consist of only extant species, yet they allow
      inference of past rates of extinction, because recently originated species are
      less likely to be extinct than ancient species. Despite the simple structure of
      the assumed underlying speciation-extinction process, parametric functions to
      estimate extinction rates from phylogenies turned out to be complex and often
      difficult to derive. Moreover, these parametric functions are specific to a
      particular process (e.g. complete species level phylogeny with constant birth and
      death rates) and a particular type of data (e.g. times between bifurcations).
      Here, it is shown that artificial neural networks can substitute for parametric
      estimation functions once they have been sufficiently trained on simulated data.
      This technique can in principle be used for different processes and data types,
      and because it circumvents the time-consuming and difficult task of deriving
      parametric estimation functions, it may greatly extend the possibilities to make
      macro-evolutionary inferences from molecular phylogenies. This novel approach is
      explained, applied to estimate speciation and extinction rates from a molecular
      phylogeny of the reef fish genus Naso (Acanturidae), and its performance is
      compared to that of maximum likelihood estimation.

PMID- 16901509
TI  - Active linking in evolutionary games.
AB  - In the traditional approach to evolutionary game theory, the individuals of a
      population meet each other at random, and they have no control over the frequency
      or duration of interactions. Here we remove these simplifying assumptions. We
      introduce a new model, where individuals differ in the rate at which they seek
      new interactions. Once a link between two individuals has formed, the
      productivity of this link is evaluated. Links can be broken off at different
      rates. In a limiting case, the linking dynamics introduces a simple
      transformation of the payoff matrix. We outline conditions for evolutionary
      stability. As a specific example, we study the interaction between cooperators
      and defectors. We find a simple relationship that characterizes those linking
      dynamics which allow natural selection to favour cooperation over defection.

PMID- 16901510
TI  - Selection for mutational robustness in finite populations.
AB  - We investigate the evolutionary dynamics of a finite population of RNA sequences
      replicating on a neutral network. Despite the lack of differential fitness
      between viable sequences, we observe typical properties of adaptive evolution,
      such as increase of mean fitness over time and punctuated-equilibrium
      transitions, after initial mutation-selection balance has been reached. We find
      that a product of population size and mutation rate of approximately 30 or larger
      is sufficient to generate selection pressure for mutational robustness, even if
      the population size is orders of magnitude smaller than the neutral network on
      which the population resides. Our results show that quasispecies effects and
      neutral drift can occur concurrently, and that the relative importance of each is
      determined by the product of population size and mutation rate.

PMID- 16901512
TI  - Mercury flux to estuarine sediments, derived from Pb-210 and Cs-137
      geochronologies (Guaratuba Bay, Brazil).
AB  - A sediment core from Guaratuba Bay was used to indicate possible Hg modifications
      to this coastal environment brought about by growing agricultural activity.
      Sedimentation rates were estimated to be 6.1 mm/year and 5.2 mm/year through
      210Pb and 137Cs geochronologies, respectively. Mercury concentrations and organic
      matter ratios in the surface layers are greater than in the older sediments,
      supporting the hypothesis of anthropogenic enrichment. Results show that the Hg
      flux has raised more than twofold during the second half of the 20th century.
      These results point to the need for further studies to substantiate the
      hypothesis of anthropogenic enrichment and to quantify point sources of Hg to
      this estuary.

PMID- 16901511
TI  - Organic carbon and nitrogen stable isotopes in the intertidal sediments from the
      Yangtze Estuary, China.
AB  - The natural isotopic compositions and C/N elemental ratios of sedimentary organic
      matter were determined in the intertidal flat of the Yangtze Estuary. The results
      showed that the ratios of carbon and nitrogen stable isotopes were respectively 
      29.8 per thousand to -26.0 per thousand and 1.6 per thousand-5.5 per thousand in
      the flood season (July), while they were -27.3 per thousand to -25.6 per thousand
      and 1.7 per thousand-7.8 per thousand in the dry season (February), respectively.
      The delta(13)C signatures were remarkably higher in July than in February, and
      gradually increased from the freshwater areas to the brackish areas. In contrast,
      there were relatively complex seasonal and spatial changes in stable nitrogen
      isotopes. It was also reflected that delta(15)N and C/N compositions had been
      obviously modified by organic matter diagenesis and biological processing, and
      could not be used to trace the sources of organic matter at the study area. In
      addition, it was considered that the mixing inputs of terrigenous and marine
      materials generally dominated sedimentary organic matter in the intertidal flat.
      The contribution of terrigenous inputs to sedimentary organic matter was roughly
      estimated according to the mixing balance model of stable carbon isotopes.

PMID- 16901513
TI  - Neuroanatomical and pharmacological assessment of Fos expression induced in the
      rat brain by the phosphodiesterase-4 inhibitor 6-(4-pyridylmethyl)-8-(3
      nitrophenyl) quinoline.
AB  - A major obstacle in the therapeutic development of phosphodiesterase-4 (PDE4)
      inhibitors is the production of adverse side effects such as nausea and vomiting.
      Immunohistochemical detection of Fos-like immunoreactivity (FLI) was used to
      address the neuroanatomical basis for the pharmacological actions of PDE4
      inhibitors. The potent and selective PDE4 inhibitors 6-(4-pyridylmethyl)-8-(3
      nitrophenyl) quinoline (PMNPQ) and rolipram elevated FLI in brain regions
      potentially relevant to the anti-depressant and emetic effects of PDE4
      inhibition. PMNPQ and rolipram elevated FLI in the locus coeruleus, habenula,
      paraventricular nucleus of the thalamus, amygdala and nucleus accumbens, all
      structures with strong limbic connectivity implicated in arousal, memory and
      affective aspects of behaviour. Consistent with the emetic effects of PDE4
      inhibitors such as PMNPQ and rolipram, these compounds elevated FLI in caudal
      brainstem nuclei such as the area postrema and nucleus of the solitary tract.
      Administration of the NK(1) antagonist RP 67580 prior to PMNPQ reversed increases
      in FLI produced by PMNPQ in these regions. RP 67580 did not, however, reduce
      PMNPQ-induced FLI in limbic structures. These findings suggest that PDE4
      inhibitors produce emesis by increasing NK(1) receptor activation in the AP/NTS
      and implicate brain regions associated with reward and mood such as the amygdala,
      paraventricular nucleus of the thalamus, habenula and nucleus accumbens in the
      anti-depressant activity of such compounds.

PMID- 16901514
TI  - The role of NMDAR subtypes and charge transfer during hippocampal LTP induction.
AB  - Activation of NMDA receptors (NMDARs) is a requirement for persistent synaptic
      alterations, such as long-term potentiation of synaptic transmission (LTP).
      NMDARs are composed of NR1 and NR2 subunits, and NR2 subunit-dependent gating
      properties of NMDAR subtypes cause dramatic differences in the timing of charge
      transfer. These postsynaptic temporal profiles are further influenced by the
      frequency of synaptic activation. Here, we investigated in the CA1 region of
      hippocampal slices from P28 mice, whether particular NMDAR subtypes are recruited
      based on NR2 subunit-specific gating following different induction protocols. For
      high frequency afferent stimulation (HFS), we found that genetic impairment of
      NR2A or pharmacological block of NR2A- or NR2B-type NMDARs can reduce field LTP.
      In contrast, when pairing low frequency synaptic stimulation with postsynaptic
      depolarization (LFS pairing) in single CA1 neurons, pharmacological antagonism of
      either subtype modestly reduced the charge transfer during LFS pairing without
      reducing the LTP magnitude. These results indicate that HFS-triggered LTP is
      induced by more than one NMDAR subtype, whereas a single subtype is sufficient
      during LFS pairing. Analysis of charge transfer during LFS pairing in 13
      different conditions revealed a threshold for LTP induction, which was
      independent of the NR2 antagonist tested. Thus, at least for LFS pairing, the
      amount of charge transfer, and thus Ca2+ influx, during LTP induction is a factor
      more critical than the participation of a particular NMDAR subtype.

PMID- 16901515
TI  - Effects of non-competitive AMPA receptor antagonists injected into some brain
      areas of WAG/Rij rats, an animal model of generalized absence epilepsy.
AB  - CFM-2 [1-(4-aminophenyl)-3,5-dihydro-7,8-dimethoxy-4H-2,3-benzodiazepin-4-one]
      and THIQ-10c [N-acetyl-1-(4-chlorophenyl)-6,7-dimethoxy-1,2,3,4
      tetrahydroisoquinoline], are two non-competitive 2-amino-3-(3-hydroxy-5
      methylisoxazol-4-yl) propionic acid (AMPA) receptor antagonists, which
      demonstrated to antagonize generalized tonic-clonic seizures in different animal
      models. We have evaluated the effects of such compounds in a genetic animal model
      of absence epilepsy, the WAG/Rij rat. Animals were focally microinjected into
      specific brain areas of the cortico-thalamic circuit in order to evaluate the
      effects of these compounds on the number and duration of epileptic spike-wave
      discharges (SWDs) and better characterize the role of AMPA neurotransmission in
      this animal model. The focal microinjection of the two AMPA antagonists into some
      thalamic nuclei (ventralis posteromedialis (VPM), reticularis (NRT), ventralis
      posterolateralis (VPL) and the primary somatosensory forelimb region (S1FL)) was,
      generally, not able to significantly modify the occurrence of SWDs. Whereas, both
      compounds were able to reduce the number and duration of SWDs dose-dependently
      when microinjected into the peri-oral region of the primary somatosensory cortex
      (S1po). These findings suggest that AMPA receptor antagonists might play a role
      in absence epilepsies and that it might depend on the involvement of specific
      neuronal areas.

PMID- 16901517
TI  - Blockade of group II metabotropic glutamate receptors in the nucleus accumbens
      produces hyperlocomotion in rats previously exposed to amphetamine.
AB  - The neurotransmitter glutamate is known to participate in both the induction and
      expression of locomotor sensitization by psychostimulant drugs like amphetamine.
      Previously, it was reported that subtype nonselective blockade of metabotropic
      glutamate receptors (mGluRs) in the nucleus accumbens (NAcc) produces
      hyperlocomotion in rats previously exposed to amphetamine. The present
      experiments examined whether group II mGluRs may contribute to this effect. Rats
      in different groups were administered five injections of either saline or
      amphetamine (1.0 mg/kg, i.p.), one injection given every third day. Two weeks
      later, they were tested for 2 h following an injection of either saline or the
      group II mGluR antagonist LY341495. In one experiment, test injections were
      administered systemically (saline or LY341495, 1.0 mg/kg, i.p.). Rats previously
      exposed to amphetamine showed a greater locomotor response to LY341495 on the
      test compared to controls previously exposed to saline. This hyperlocomotor
      response was absent in rats tested with a combination of LY341495 and the group
      II mGluR agonist LY379268 (1.0 mg/kg, i.p.). In a second experiment, different
      rats were tested following microinjections into the NAcc (saline or LY341495,
      0.1, 10 or 100 microg/0.5 microl/side). Again, rats previously exposed to
      amphetamine showed a greater dose-dependent locomotor response to LY341495 on the
      test relative to saline-exposed controls. Locomotor activity in saline-exposed
      rats challenged with LY341495 did not differ from that observed in rats
      previously exposed and tested with saline in either experiment. These results
      indicate that group II mGluRs, particularly those found in the NAcc, are well
      positioned to modulate the expression of locomotor sensitization by amphetamine.

PMID- 16901516
TI  - A slow-onset, long-duration indanamine monoamine reuptake inhibitor as a
      potential maintenance pharmacotherapy for psychostimulant abuse: effects in
      laboratory rat models relating to addiction.
AB  - Slow-onset, long-lasting dopamine reuptake blockers with reduced abuse potential
      have been suggested as maintenance therapies for cocaine addiction. We have
      synthesized a series of 3-(3',4'-dichlorophenyl)-1-indanamine monoamine reuptake
      inhibitors as candidates for such maintenance pharmacotherapy. The initial lead
      compound, the N,N-dimethyl analogue 30,640 was then subjected to testing in
      addiction-relevant animal models. Compound 30,640 (2 mg/kg i.p.) produced a
      pronounced slow-onset, long-lasting increase (300-400%) in extracellular nucleus
      accumbens dopamine levels, as measured by in vivo brain microdialysis in awake
      laboratory rats. Slow-onset, long-lasting decreases (40-80%) in the dopamine
      metabolites 3,4-dihydroxyphenylacetic acid and homovanillic acid, and the
      serotonin metabolite 5-hydroxyindoleacetic acid were also seen. Compound 30,640
      (3 or 5 mg/kg i.p.) also produced a significant (approximately 30%) slow-onset,
      long-lasting enhancement of electrical brain-stimulation reward, which was
      additive with that of cocaine (5 mg/kg i.p.). When given to cocaine-administering
      rats, 30,640 (2.5, 3, 5, or 10 mg/kg i.p.) significantly inhibited (30-60%)
      intravenous cocaine self-administration, with a pronounced long-lasting profile.
      In sum, 30,640 showed cocaine-like effects, but with a marked slow-onset, long
      lasting profile. We conclude that the prodrug strategy employed in the design of
      30,640 achieved its goal. We suggest that such compounds may be useful as
      maintenance pharmacotherapies for psychostimulant addiction.

PMID- 16901519
TI  - The mnemonic mechanisms of errorless learning.
AB  - Errorless learning enhances memory relative to errorful, trial-and-error
      learning, but the extent to which this advantage relies on implicit or explicit
      memory processes is not clear. Previous attempts to determine the mnemonic
      mechanisms of errorless learning have relied on contrasts between patient groups
      or between tasks, but both approaches are problematic. In this study, healthy
      younger and older adults were engaged in errorless or errorful learning using a
      process dissociation procedure that provides separate estimates of explicit
      recollection and implicit familiarity within-subjects and within-task (Hay &
      Jacoby, 1996). Consistent with much prior research, we found an age-related
      decrement in recollection, but age-invariance in familiarity. In the young
      adults, errorless learning reduced the misleading familiarity of prior errors,
      but this benefit was offset by the non-elaborative nature of the errorless
      learning condition that also reduced recollection. In the older adults, who are
      less able to oppose familiarity-based errors because of their lower recollection,
      errorless learning only reduced the misleading impact of previous errors. Our
      results support Baddeley and Wilson's (1994) position that the errorless learning
      effect is mediated by implicit memory processes: individuals with reduced
      explicit memory benefit from errorless learning because errorless learning
      bypasses the need to engage explicit error elimination processes. We do not
      recommend standard errorless learning for individuals with intact explicit
      memory, such as students trying to learn information in preparation for an
      examination.

PMID- 16901518
TI  - Protection against MDMA-induced dopaminergic neurotoxicity in mice by
      methyllycaconitine: involvement of nicotinic receptors.
AB  - Methylenedioxymethamphetamine (MDMA) is a relatively selective dopaminergic
      neurotoxin in mice. Previous studies demonstrated the participation of alpha-7
      nicotinic receptors (nAChR) in the neurotoxic effect of methamphetamine. The aim
      of this paper was to study the role of this receptor type in the acute effects
      and neurotoxicity of MDMA in mice. In vivo, methyllycaconitine (MLA), a specific
      alpha-7 nAChR antagonist, significantly prevented MDMA-induced neurotoxicity at
      dopaminergic but not at serotonergic level, without affecting MDMA-induced
      hyperthermia. Glial activation was also fully prevented by MLA. In vitro, MDMA
      induced intrasynaptosomal reactive oxygen species (ROS) generation, which was
      calcium-, nitric-oxide synthase-, and protein kinase C-dependent. Also, the
      increase in ROS was prevented by MLA and alpha-bungarotoxin. Experiments with
      reserpine point to endogenous dopamine (DA) as the main source of MDMA-induced
      ROS. MLA also brought the MDMA-induced inhibition of [3H]DA uptake down, from 73%
      to 11%. We demonstrate that a coordinated activation of alpha-7 nAChR, blockade
      of DA transporter function and displacement of DA from intracellular stores
      induced by MDMA produces a neurotoxic effect that can be prevented by MLA,
      suggesting that alpha-7 nAChR have a key role in the MDMA neurotoxicity in mice;
      however, the involvement of nicotinic receptors containing the beta2 subunit
      cannot be conclusively ruled out.

PMID- 16901520
TI  - The nature of memory related activity in early visual areas.
AB  - Memory for visual items can evoke activity in visual processing regions, which is
      typically assumed to reflect conscious remembering. However, based on previous
      findings, we hypothesized that such activity in early visual areas (BA17, BA18)
      may reflect priming, a form of nonconscious memory. We tested this hypothesis in
      two fMRI experiments with similar stimulus protocols, but explicit or implicit
      task instructions. During initial runs, abstract shapes were presented to either
      side of fixation, filled with parallel lines of random orientation and color. In
      subsequent runs, old and new shapes (plus related shapes in Experiment 2) were
      presented at fixation. In Experiment 1, participants were instructed to remember
      each shape and its spatial location during initial runs; during subsequent runs
      they classified each shape as old and on the "left", old and on the "right", or
      "new". A right fusiform gyrus region (BA18) and a left lingual gyrus region
      (BA18) were preferentially associated with shapes previously presented on the
      left and right, respectively. In support of our hypothesis, this early visual
      area activity was independent of response accuracy for spatial location. In
      Experiment 2, for each shape, participants identified parallel line orientation
      relative to horizontal. Consistent with our hypothesis, specific neural activity
      was observed in early visual regions (BA17, BA18, extending into BA19), with old
      activity greater than related and new activity (likely reflecting priming). The
      results of these experiments provide convergent evidence that memory related
      early visual area activity (BA17, BA18) can reflect nonconscious processing.

PMID- 16901521
TI  - Neural correlates of imagined and synaesthetic colours.
AB  - The experience of colour is a core element of human vision. Colours provide
      important symbolic and contextual information not conveyed by form alone.
      Moreover, the experience of colour can arise without external stimulation. For
      many people, visual memories are rich with colour imagery. In the unusual
      phenomenon of grapheme-colour synaesthesia, achromatic forms such as letters,
      words and numbers elicit vivid experiences of colour. Few studies, however, have
      examined the neural correlates of such internally generated colour experiences.
      We used functional magnetic resonance imaging (fMRI) to compare patterns of
      cortical activity for the perception of external coloured stimuli and internally
      generated colours in a group of grapheme-colour synaesthetes and matched non
      synaesthetic controls. In a voluntary colour imagery task, both synaesthetes and
      non-synaesthetes made colour judgements on objects presented as grey scale
      photographs. In a synaesthetic colour task, we presented letters that elicited
      synaesthetic colours, and asked participants to perform a localisation task. We
      assessed the neural activity underpinning these two different forms of colour
      experience that occur in the absence of chromatic sensory input. In both
      synaesthetes and non-synaesthetes, voluntary colour imagery activated the colour
      selective area, V4, in the right hemisphere. In contrast, the synaesthetic colour
      task resulted in unique activity for synaesthetes in the left medial lingual
      gyrus, an area previously implicated in tasks involving colour knowledge. Our
      data suggest that internally generated colour experiences recruit brain regions
      specialised for colour perception, with striking differences between voluntary
      colour imagery and synaesthetically induced colours.

PMID- 16901523
TI  - Copulatory organ musculature in Childia (Acoela) as revealed by phalloidin
      fluorescence and confocal microscopy.
AB  - Copulatory organs of eight species of the monophyletic taxon Childia were
      investigated in detail, using phalloidin fluorescence method and confocal
      microscopy. Childia species were shown to have one, two or several tubular
      stylets, conical to cylindrical in shape, composed of few to numerous needles.
      The musculature varied greatly, from the absence of seminal vesicle to
      extensively developed seminal vesicles with several additional types of
      specialized muscles. Ten copulatory organ characters were coded and mapped on the
      total evidence tree. The data obtained permitted to follow the evolution of the
      Childia stylet and to demonstrate that the structure of the stylet apparatus is
      largely consistent with the phylogeny of the group (CI=0.75). Possible function
      of different muscle specializations was discussed.

PMID- 16901522
TI  - An alpha-amylase inhibitor gene from Phaseolus coccineus encodes a protein with
      potential for control of coffee berry borer (Hypothenemus hampei).
AB  - Plant alpha-amylase inhibitors are proteins found in several plants, and play a
      key role in natural defenses. In this study, a gene encoding an alpha-amylase
      inhibitor, named alphaAI-Pc1, was isolated from cotyledons of Phaseolus
      coccineus. This inhibitor has an enhanced primary structure to P. vulgaris alpha
      amylase inhibitors (alpha-AI1 and alpha-AI2). The alphaAI-Pc1 gene, constructed
      with the PHA-L phytohemaglutinin promoter, was introduced into tobacco plants,
      with its expression in regenerated (T0) and progeny (T1) transformant plants
      monitored by PCR amplification, enzyme-linked immunosorbent assay (ELISA) and
      immunoblot analysis, respectively. Seed protein extracts from selected
      transformants reacted positively with a polyclonal antibody raised against
      alphaAI-1, while no reaction was observed with untransformed tobacco plants.
      Immunological assays showed that the alphaAI-Pc1 gene product represented up to
      0.05% of total soluble proteins in T0 plants seeds. Furthermore, recombinant
      alphaAI-Pc1 expressed in tobacco plants was able to inhibit 65% of digestive H.
      hampei alpha-amylases. The data herein suggest that the protein encoded by the
      alphaAI-Pc1 gene has potential to be introduced into coffee plants in order to
      increase their resistance to the coffee berry borer.

PMID- 16901524
TI  - Function of Spodoptera exigua nucleopolyhedrovirus late gene expression factors
      in the insect cell line SF-21.
AB  - We used a well established transient expression assay to test the ability of the
      baculovirus Spodoptera exigua M nucleopolyhedrovirus (SeMNPV) homologs of
      Autographa californica MNPV (AcMNPV) late expression factors (lefs) to activate a
      late promoter-reporter gene cassette in SF-21 cells. This insect-derived cell
      line is fully permissive for AcMNPV infection but not for SeMNPV. In the assay,
      19 AcMNPV lefs stimulate optimal levels of late gene promoter activity. SeMNPV
      lef-5 successfully replaced the corresponding AcMNPV gene in the context of the
      remaining set of AcMNPV lefs, whereas SeMNPV dnapol and 39k exhibited partial
      activity. When all the SeMNPV lefs were assayed together or in the presence of
      four lefs encoded only in AcMNPV, it resulted in background levels of late
      promoter-driven reporter gene activity. However, SeMNPV genomic DNA and the four
      AcMNPV-specific lefs stimulated low levels of reporter gene activity. Moreover,
      SeMNPV IE-1, but not AcMNPV IE-1, further stimulated late gene expression in the
      presence of SeMNPV DNA. AcMNPV IE-1 was able to mediate early gene expression cis
      linked to homologous regions (hrs) derived from AcMNPV and SeMNPV. In contrast,
      SeMNPV IE-1 was more specific for SeMNPV-derived hr elements.

PMID- 16901525
TI  - Gaze distractors influence saccadic curvature: evidence for the role of the
      oculomotor system in gaze-cued orienting.
AB  - We examined the role of the oculomotor system in gaze-triggered orienting of
      attention by measuring whether perceiving of task-irrelevant gaze distractors and
      peripheral spatial distractors influence saccadic curvature similarly.
      Participants performed reflexive, vertical saccades to designated target areas
      while their eye movements were recorded. Schematic faces with averted gaze or
      peripheral boxes were presented before or simultaneously (-100 ms/0 ms SOAs) with
      the imperative signal. Gaze distractors caused the saccades to curve away from
      the distractor direction at both SOAs and peripheral distractors only at the 0-ms
      SOA. The results imply that gaze-cued shifts of visual attention involve both
      cortical attention orienting systems and subcortical oculomotor systems.

PMID- 16901526
TI  - Study on Fe(VI) species as a disinfectant: quantitative evaluation and modeling
      for inactivating Escherichia coli.
AB  - Ferrate (Fe(VI)) has high potentials as a multi-purpose water treatment chemical
      acting as an oxidant, coagulant, and disinfectant, but little detail has been
      reported concerning its biocidal ability. In this study, the inactivation
      efficiencies of three Fe(VI) species (H(x)FeO(4)(x-2), x=0, 1, 2) are quantified
      using Escherichia coli as a model microorganism. E. coli inactivation by Fe(VI)
      was performed in solutions buffered with 25 mM phosphate in the pH range of 5.6
      8.2 and at 25 degrees C. Kinetics of E. coli inactivation were successfully
      fitted to the Modified Delayed Chick-Watson model in the tested pH range,
      indicating that log inactivation level of E. coli is linearly proportional to
      exposure amount of E. coli to Fe(VI). The rate constant of E. coli inactivation
      by Fe(VI) (k(obs)) that was obtained from the linear regression increased non
      linearly from 0.33 to 6.25 l(mg min)(-1) with decreasing pH from 8.2 to 5.6. From
      the measured pH dependency of k(obs) and the known acidity constants of Fe(VI)
      species (pK(a), H(2)FeO(4)=3.50 and pK(a), HFeO(4)(-)=7.23), HFeO(4)(-) and
      H(2)FeO(4) were found to be 3 and 265 times as effective as FeO(4)(2-) in E. coli
      inactivation, respectively.

PMID- 16901527
TI  - Multidimensional modelling to investigate interspecies hydrogen transfer in
      anaerobic biofilms.
AB  - Anaerobic digestion is a multistep process, mediated by a functionally and
      phylogenetically diverse microbial population. One of the crucial steps is
      oxidation of organic acids, with electron transfer via hydrogen or formate from
      acetogenic bacteria to methanogens. This syntrophic microbiological process is
      strongly restricted by a thermodynamic limitation on the allowable hydrogen or
      formate concentration. In order to study this process in more detail, we
      developed an individual-based biofilm model which enables to describe the
      processes at a microbial resolution. The biochemical model is the ADM1,
      implemented in a multidimensional domain. With this model, we evaluated three
      important issues for the syntrophic relationship: (i) Is there a fundamental
      difference in using hydrogen or formate as electron carrier? (ii) Does a
      thermodynamic-based inhibition function produced substantially different results
      from an empirical function? and; (iii) Does the physical co-location of acetogens
      and methanogens follow directly from a general model. Hydrogen or formate as
      electron carrier had no substantial impact on model results. Standard inhibition
      functions or thermodynamic inhibition function gave similar results at larger
      substrate field grid sizes (> 10 microm), but at smaller grid sizes, the
      thermodynamic-based function reduced the number of cells with long interspecies
      distances (> 2.5 microm). Therefore, a very fine grid resolution is needed to
      reflect differences between the thermodynamic function, and a more generic
      inhibition form. The co-location of syntrophic bacteria was well predicted
      without a need to assume a microbiological based mechanism (e.g., through
      chemotaxis) of biofilm formation.

PMID- 16901528
TI  - Reduction of nitrobenzene and formation of corrosion coatings in zerovalent iron
      systems.
AB  - Batch tests were conducted to investigate reduction of nitrobenzene in a
      zerovalent iron system (Fe0) under various conditions. The results indicated that
      a limited amount of nitrobenzene (ArNO2) could be reduced to aniline by Fe0, but
      formation of a lepidocrocite (gamma-FeOOH) coating could significantly slow down
      the reaction. However, augmenting Fe0 with substoichiometric FeCl2 could
      dramatically accelerate the reaction. Surface-adsorbed Fe(II), not pH nor Cl-,
      was found to be responsible for rejuvenating the system. O2 and nitrobenzene
      could be concomitantly reduced by Fe0 in the presence of Fe2+. In the Fe0 system,
      both nitrobenzene and O2 favored formation of lepidocrocite; in the presence of
      aq. Fe(II), a stratified corrosion coating could develop, with magnetite (Fe3O4)
      as the inner layer and lepidocrocite as the outer layer. Fe2+ was not the main
      reductant for the reactions, but might accelerate the autoreduction of
      lepidocrocite to magnetite by the underlying Fe0. Our understanding on the role
      of Fe(II) in conjunction with a stratified, evolving corrosion coating may be
      useful for establishing an iron aquatic corrosion model.

PMID- 16901529
TI  - Electrochemical determination of 2-chlorophenol using an acetylene black film
      modified glassy carbon electrode.
AB  - Herein, an insoluble acetylene black (AB) was dispersed into water in the
      presence of a special kind of surfactant: dihexadecyl hydrogen phosphate (DHP),
      resulting in a homogeneous and stable AB-DHP suspension. Thus, a novel AB-DHP
      composite film coated glassy carbon electrode (GCE) was fabricated via coating
      technology. Additionally, the electrochemical behaviors of 2-chlorophenol at bare
      GCE, DHP-modifed GCE, and AB-DHP modified GCE were investigated, respectively.
      Compared with the unmodified and DHP-coated GCE, the AB-DHP film-modified GCE
      significantly enhances the oxidation peak current of 2-chlorophenol, and thus
      greatly improves its determining sensitivity, suggesting that this new modified
      electrode has great potential in the determination of trace level of 2
      chlorophenol. All the experimental conditions, which affect the electrochemical
      response of 2-chlorophenol, were studied. Finally, a sensitive and simple
      voltammetric method with a good linear relationship in the range 2.0 x 10(-7)-4.0
      x 10(-5) mol/L, was developed. The detection limit of 2-chlorophenol was 5.0 x
      10(-8) mol/L for 2 min accumulation (S/N = 3). This electrode was successfully
      applied to detect 2-chlorophenol in water samples.

PMID- 16901530
TI  - Determination of PM2.5 sources using time-resolved integrated source and receptor
      models.
AB  - Multivariate statistical techniques are applied to particulate matter (PM) and
      meteorological data to identify the sources responsible for evening PM spikes at
      Sunland Park, NM (USA). The statistical techniques applied are principal
      components analysis (PCA), redundancy analysis (RDA), and absolute principal
      components scores analysis (APCSA), and the data evaluated are 3-h average (6-9
      p.m.) PM(2.5) mass and chemical composition and 1-h average PM(2.5) and PM(10)
      mass and environmental data collected in the winter of 2002. Although the
      interpretation of the data was complicated by the presence of sources which are
      likely changing in time (e.g. brick kilns), the multivariate analyses indicate
      that the evening high PM(2.5) is associated with burning-activities occurring to
      the south of Sunland Park, and these emissions are characterized by elevated Sb,
      Cl(-), and elemental carbon; approximately 68% of the PM(2.5) mass can be
      attributed to this source. The PM(10) evening peaks, on the other hand, are
      mainly caused by resuspended dust generated by vehicular movements south of the
      site and transported by the local terrain-induced drainage flow.

PMID- 16901531
TI  - Genotoxicity of organic extracts of urban airborne particulate matter: an
      assessment within a personal exposure study.
AB  - Airborne particulate matter, PM(10) and PM(2.5), are associated with a range of
      health effects including lung cancer. Their complex organic fraction contains
      genotoxic and carcinogenic compounds such as polycyclic aromatic hydrocarbons
      (PAHs) and their derivatives. This study evaluates the genotoxicity of the PM(10)
      and PM(2.5) organic extracts that were sampled in the framework of a personal
      exposure study in three French metropolitan areas (Paris, Rouen and Strasbourg),
      using the comet assay, performed on HeLa S3 cells. In each city, 60-90 non
      smoking volunteers composed of two groups of equal size (adults and children)
      carried the personal Harvard Chempass multi-pollutant sampler during 48h along
      two different seasons ('hot' and 'cold'). Volunteers were selected so as to live
      (home and work/school) in 3 different urban sectors contrasted in terms of air
      pollution within each city (one highly exposed to traffic emissions, one
      influenced by local industrial sources, and a background urban environment).
      Genotoxic effects are stronger for PM(2.5) extracts than for PM(10), and greater
      in winter than in summer. Fine particles collected by subjects living within the
      traffic proximity sector present the strongest genotoxic responses, especially in
      the Paris metropolitan area. This work confirms the genotoxic potency of
      particulate matter (PM(10) and PM(2.5)) organic extracts to which urban
      populations are exposed.

PMID- 16901532
TI  - HPA function in adolescence: role of sex hormones in its regulation and the
      enduring consequences of exposure to stressors.
AB  - The hypothalamic-pituitary-adrenal (HPA) axis is one of the physiological systems
      involved in coping with stressors. There are functional shifts in the HPA axis
      and its regulation by sex hormones over the lifespan that allow the animal to
      meet the challenges of the internal and external environment that are specific to
      each stage of development. Sex differences in HPA function emerge over
      adolescence, a phenomenon reflecting the concomitant initiation of regulatory
      effects of sex hormones. The focus of this review is recent research on
      differences between adolescents and adults in HPA function and the enduring
      effects of exposure to stressors in adolescence. During adolescence, HPA function
      is characterized by a prolonged activation in response to stressors compared to
      adulthood, which may render ongoing development of the brain vulnerable. Although
      research has been scarce, there is a growing evidence that exposure to stressors
      in adolescence may alter behavioural responses to drugs and cognitive performance
      in adulthood. However, the effects reported appear to be stressor-specific and
      sex-specific. Such research may contribute toward understanding the increased
      risk for drug abuse and psychopathology that occurs over adolescence in people.

PMID- 16901533
TI  - The economic value of reductions in gonorrhea and syphilis incidence in the
      United States, 1990-2003.
AB  - BACKGROUND: Prevention efforts can reduce the considerable health and economic
      burdens imposed by sexually transmitted diseases (STDs). The objective of this
      study was to estimate the reduction in direct medical costs associated with
      reductions in gonorrhea and syphilis incidence in the United States from 1990 to
      2003. METHODS: Using published estimates of the per-case costs of STDs, we
      estimated the annual costs from 1990 to 2003 of four main outcomes: primary and
      secondary (P&S) syphilis, congenital syphilis, gonorrhea, and HIV costs
      attributable to the facilitative effects of gonorrhea and syphilis on HIV
      transmission and acquisition. RESULTS: Reductions in syphilis and gonorrhea from
      1990 to 2003 have saved an estimated 5.0 billion dollars (in 2003 U.S. dollars):
      1.1 billion dollars in costs associated with P&S syphilis, congenital syphilis,
      and gonorrhea, and 3.9 billion dollars in HIV costs attributable to syphilis and
      gonorrhea. In additional analyses, the estimated reductions in disease burden
      were substantially lower (1) when calculated incrementally (rather than
      cumulatively) and (2) when long-term costs of STDs were excluded. CONCLUSIONS:
      These estimated reductions in the burden of gonorrhea and syphilis show the
      economic benefits of reducing the incidence of these STDs and preventing their
      resurgence.

PMID- 16901534
TI  - Prevalence and correlates of doctor-geriatric patient lifestyle discussions:
      analysis of ADEPT videotapes.
AB  - BACKGROUND: This study identifies the prevalence and correlates of physician
      geriatric patient discussions about physical activity and nutrition lifestyle
      behaviors. METHODS: Between August 1998 and July 2000, 423 older patient visits
      to 36 physicians were videotaped in three different primary care settings. The
      patient sample was primarily white, female, well-educated, and financially
      sufficient, although 12.7% of the encounters occurred in an inner city clinic.
      The major dependent variable-lifestyle discussion-is based on observations of
      physician behavior. Descriptive and multivariate logistic regression analyses
      were conducted in 2004. RESULTS: Nutrition talk was most prevalent, occurring in
      almost half the encounters (48.2%) followed by physical activity discussions
      (39.2%) then conjoint mention (22%). Discussions were significantly less likely
      to occur in acute visits. While ethnicity, gender, and length of visit were not
      significantly related, physician interaction style and patient vitality and
      education were significant predictors in the multivariate analyses. CONCLUSIONS:
      Given the impact of lifestyle behaviors on myriad health outcomes, the current
      prevalence rates of physician discussion, while higher than in many previous
      studies, remain sub-optimal. Practical assessment tools, training in behavioral
      counseling, and reimbursement incentives are recommended strategies for raising
      physical activity and nutrition discussion prevalence in primary care settings.

PMID- 16901535
TI  - Time-dependent corrosion potential of newly-placed admixed dental amalgam
      restorations.
AB  - OBJECTIVE: It was the objective of this study to measure the corrosion potential
      over time of newly-placed admixed dental amalgam restorations as a possible
      indicator of corrosion activity. METHODS: The corrosion potentials of 271 amalgam
      restorations, 4-min to 24-month old were measured in a convenience sample of 81
      subjects. The selected restorations had no occlusal or interproximal contact with
      other metallic restorations. Eighty-one percent of the restorations aged 4 min to
      7 months were made from zinc-containing admixed high-copper amalgam. The
      remaining amalgams were an unknown mixture of admixed high-copper and single
      composition-alloy amalgams. RESULTS: The data were fit to a mixed-effects model
      with random patient effects to allow for the correlation, using the maximum
      likelihood method. The early data best fit a quadratic model with an initially
      rapidly rising corrosion potential that leveled off to a constant mean value of 
      146 (60)mV (versus Ag/AgCl, 3M KCl at 35 degrees C) by approximately 7 months.
      Most of the ennoblement occurred within the first 4 months after restoration
      placement. SIGNIFICANCE: This in vivo study observed a slower rate of corrosion
      potential ennoblement for admixed amalgam restorations than would be predicted
      from in vitro studies. The slower rate is believed due to the combination of
      mechanical, chemical and biological forces in the mouth that are generally absent
      using simulated conditions. The slower rate of ennoblement suggests a slower rate
      of achieving maximum corrosion resistance than would be predicted using in vitro
      studies.

PMID- 16901536
TI  - Studies on the oridonin-loaded poly(D,L-lactic acid) nanoparticles in vitro and
      in vivo.
AB  - The purpose of this paper was to investigate the possibility of developing a
      polymeric nanoparticle delivery system for ORI to increase its solubility, blood
      circulation time and tissue targeting. Oridonin-loaded poly(D,L-lactic acid)
      nanoparticles (ORI-PLA-NP) were prepared by the further modified spontaneous
      emulsion solvent diffusion (MSESD) method. Studies were carried out to
      characterize and evaluate the produced ORI-PLA-NP both in vitro and in vivo. The
      experimental results showed that the mean size of the nanoparticles were 137.3
      nm, with 87.2% of the nanoparticles distributed between the range of 107 and 195
      nm. The entrapment efficiency and actual drug loading of the nanoparticles were
      91.88+/-1.83 and 2.32+/-0.05%, respectively. It was demonstrated by differential
      scanning calorimetry (DSC) and X-ray diffractometry (XRD) that ORI existed in the
      form of amorphous in the nanoparticles. The in vitro release profile of ORI-PLA
      NP could be expressed well by the Higuchi equation: Q=8.944t(1/2)+11.246. The
      results of pharmacokinetics demonstrated that being encapsulated in PLA
      nanoparticles was remarkably effective for ORI to prolong its blood circulation
      time. After the i.v. administration of ORI-PLA-NP, we could observe a stable and
      high concentration of ORI in liver, lung and spleen, while its distribution in
      heart and kidney decreased.

PMID- 16901537
TI  - Co-culture of human embryonic stem cells with murine embryonic fibroblasts on
      microwell-patterned substrates.
AB  - Human embryonic stem (hES) cells are generally cultured as cell clusters on top
      of a feeder layer formed by mitotically inactivated murine embryonic fibroblasts
      (MEFs) to maintain their undifferentiated state. This co-culture system, which is
      typically used to expand the population of undifferentiated hES cells, presents
      several challenges since it is difficult to control cell cluster size. Large cell
      clusters tend to differentiate at the borders, and clusters with different sizes
      may lead to heterogeneous differentiation patterns within embryoid bodies. In
      this work, we develop a new approach to culture hES cells with controlled cluster
      size and number through merging microfabrication, and biomaterials technologies.
      Polymeric microwells were fabricated and used to control the size and uniformity
      of hES cell clusters in co-culture with MEFs. The results show that it is
      possible to culture hES cells homogeneously while keeping their undifferentiated
      state as confirmed by the expression of stem cell markers octamer binding protein
      4 (Oct-4) and alkaline phosphatase (ALP). In addition, these clusters can be
      recovered from the microwells to generate nearly homogeneous cell aggregates for
      differentiation experiments.

PMID- 16901538
TI  - The effect of water uptake on the behaviour of hydrophilic cements in confined
      environments.
AB  - Physiological fluids will be in contact with the implant components from the
      first moments after a surgery. Therefore, the study of the effect of water on the
      properties of the bone cements that are part of the arthroplasty procedure is of
      critical importance to predict the long-term performance of the whole system. In
      our research group, we have developed a novel concept, the hydrophilic, partially
      degradable and bioactive cements which uptake considerably more water than
      standard bone cements. In this paper, we aimed to study the effect of water
      uptake (WU) by these cements on their behaviour. The tests were carried out in
      confined cavities, which represent more accurately the in vivo situation the
      cement will face (constrained by the bone and prosthesis surfaces). We observed
      that the equilibrium WU decreased up to 60% (as compared to non-confined
      situations), depending of the formulation. This decrease resulted in a latent
      tendency of the cements to swell, and the hindering of such swelling generated a
      swelling pressure against the constraining walls. The pressure, and consequent
      press-fitting effect, could be controlled by a number of mechanisms, and resulted
      in higher stability of the hydrophilic cements, expressed as an increase in the
      push-out force, required to extract the specimens from such constrained cavities.
      This effect was only observed in hydrophilic cements, not in commercial,
      hydrophobic ones used as controls. We conclude that such cements will provide an
      additional and very useful source of immediate adhesion in the short-term after
      surgery: water induced press fitting.

PMID- 16901539
TI  - Hydroxyl-containing antimony oxide bromide nanorods combined with chitosan for
      biosensors.
AB  - A hydroxyl-containing antimony oxide bromide (AOB) nanorods was synthesized by a
      hydrothermal method. TEM and SEM images showed that the as-prepared AOB nanorods
      were very copious with diameters of about 50 nm. The AOB nanorods could be easily
      combined with biopolymer chitosan (Chi) to form an organic-inorganic hybrid
      material, and a biocompatible, crack-free and porous Chi-AOB composite film could
      be readily obtained. Horseradish peroxidase (HRP) was chosen as a model protein
      to construct a reagentless mediator-free third-generation HRP biosensor. UV
      visible and FTIR spectroscopy revealed that HRP entrapped in the composite film
      could retain its native secondary structure. A pair of stable and well-defined
      redox peaks of HRP with a formal potential of about -0.24 V (vs. Ag/AgCl) in a pH
      7.0 phosphate-buffered solution (PBS) were obtained at the HRP-Chi-AOB composite
      film modified glassy carbon (GC) electrode. With advantages of organic-inorganic
      hybrid materials, dramatically facilitated direct electron transfer of HRP and
      excellent bioelectrocatalytic activity towards H(2)O(2) were demonstrated. The
      apparent Michaelis-Menten constant K(M)(app) was calculated to be 7.5mum,
      indicating that HRP entrapped in the composite film possessed high affinity to
      H(2)O(2) and exhibited high enzymatic activity. The prepared biosensor displayed
      good sensitivity and reproducibility, wide linear range, low detection limit,
      fast response and excellent long-term stability. The Chi-AOB composite film could
      be used efficiently for the entrapment of other redox-active proteins and may
      find wide potential applications in biosensors, biocatalysis, biomedical devices
      and bioelectronics.

PMID- 16901540
TI  - The effect of collagen-targeting platelet-derived growth factor on
      cellularization and vascularization of collagen scaffolds.
AB  - Platelet-derived growth factor BB (PDGF-BB) was an important inductive factor
      during wound healing, but the lack of efficient delivery system limited its
      clinical application. Here, a peptide of seven amino acids was firstly utilized
      to engineer PDGF-BB to construct a collagen-targeting system. This peptide
      functioned as collagen-binding domain (CBD) to specially target the PDGF-BB to
      the collagen and restrict its diffusion. In our study, in vitro activity assay
      showed that the CBD-fused PDGF (CBD-PDGF) and native PDGF (NAT-PDGF) possessed
      similar activity to stimulate the human fibroblast proliferation. As expected,
      this peptide promoted the binding of PDGF to collagen scaffolds, and CBD-PDGF
      caused more cells to proliferate on the collagen gel than NAT-PDGF when the same
      amounts of PDGF were added. In the in vivo experiment, CBD-PDGF-loaded collagen
      scaffolds were uniformly cellularized and vascularized compared to that of NAT
      PDGF-loaded scaffolds. Our study demonstrated that the CBD targeted PDGF to the
      collagen scaffold to exert its functions, and it suggested this could be an
      effective system for targeting tissue regeneration and wound repair.

PMID- 16901541
TI  - Complete nucleotide sequence of pBMB67, a 67-kb plasmid from Bacillus
      thuringiensis strain YBT-1520.
AB  - The complete nucleotide sequence of a large (67kb) cryptic plasmid pBMB67 from
      Bacillus thuringiensis strain YBT-1520 was determined. Of the 74 predicted open
      reading frames (ORFs), 25 (34%) were assigned putative functions, 18 (24%)
      encoded conserved hypothetical proteins, and 31 (42%) had no homology to any
      genes present in the current open databases. The ORFs with similar functions were
      organized in a modular structure; thus, the DNA sequence of pBMB67 could be
      functionally divided into three modules, including a 39kb transfer region
      encoding homologs of the Agrobacterium tumefaciens VirB/D4 system components
      VirB1, VirB4, VirB11, and VirD4, as well as homologs of Gram-positive conjugation
      proteins. We also found a potential operon that was analogous to the Rap-Phr
      cassettes from Bacillus subtilis, which are involved in cell-cell communication
      and transcriptional regulation. Thus, we suggest that pBMB67 is likely to be
      implicated in cell-cell signaling and plays a role in the regulation of several
      cellular processes, with the production of exoprotease being one of the
      candidates.

PMID- 16901542
TI  - The correlative triad among aging, dopamine, and cognition: current status and
      future prospects.
AB  - The brain neuronal systems defined by the neurotransmitter dopamine (DA) have
      since long a recognized role in the regulation of motor functions. More recently,
      converging evidence from patient studies, animal research, pharmacological
      intervention, and molecular genetics indicates that DA is critically implicated
      also in higher-order cognitive functioning. Many cognitive functions and multiple
      markers of striatal and extrastriatal DA systems decline across adulthood and
      aging. Research examining the correlative triad among adult age, DA, and
      cognition has found strong support for the view that age-related DA losses are
      associated with age-related cognitive deficits. Future research strategies for
      examining the DA-cognitive aging link include assessing (a) the
      generality/specificity of the effects; (b) the relationship between
      neuromodulation and functional brain activation; and (c) the release of DA during
      actual task performance.

PMID- 16901543
TI  - The CD40-induced protection against CD95-mediated apoptosis is associated with a
      rapid upregulation of anti-apoptotic c-FLIP.
AB  - CD95/Fas and CD40 receptors are important regulators of cell survival during
      germinal center reaction. In this study we used a human follicular lymphoma cell
      line, HF1A3, to study molecular mechanisms of CD95-mediated apoptosis and CD40
      induced rescue from apoptosis. CD95 stimulation induced activation of caspase-8
      and -3, collapse of mitochondrial membrane potential (DeltaPsim), release of
      cytochrome c and fragmentation of nuclear DNA. All these apoptotic events were
      abrogated, when cells were pretreated with CD40 antibodies before CD95
      stimulation. CD40 induced a rapid up regulation of both short and long isoforms
      of c-FLIP, as these proteins were detectable 4h after receptor stimulation. The
      induction of c-FLIP as well as the anti-apoptotic function of CD40 was completely
      abolished when NF-kappaB activity was inhibited by a selective inhibitor PDTC. We
      conclude that the anti-apoptotic signaling of CD40 involves NF-kappaB-mediated
      induction of c-FLIP proteins which can interfere with caspase-8 activation.
      However, it remains to be seen whether c-FLIP proteins are the only one ones
      involved in CD40-mediated protection.

PMID- 16901546
TI  - PAGE separation of hemi-methylated or unmethylated oligonucleotide substrates to
      distinguish between maintenance and de novo DNA methyltranferase activity.
AB  - DNA methyltransferase (DNMT) enzymes catalyze the addition of a methyl group to
      cytosine residues in DNA. Appropriate cytosine methylation of CpG dinucleotides
      is required for normal mammalian development and homeostasis, and quantitative
      methods are necessary to assess DNMT activity in various cell extracts. The
      method described in this report utilizes incorporation of S-[methyl-(3)H]
      adenosyl-L-methionine into hemi-methylated or unmethylated oligonucleotides to
      distinguish between maintenance and de novo DNMT activity, respectively. However,
      unlike previously described methods, this protocol uses native polyacrylamide gel
      electrophoresis to detect the incorporation of radioactivity into substrate
      oligonucleotides. This approach distinguishes between incorporation of
      radioactivity into target substrate oligonucleotides and incorporation into non
      specific cellular DNA that often contaminates nuclear extracts, and permits the
      reproducible quantitation and comparison of de novo and maintenance DNMT
      activities in various cell lines. Electrophoretic separation of the methylated
      substrates is a cost-effective, specific, and reproducible approach to quantitate
      DNMT activities in nuclear extracts.

PMID- 16901544
TI  - Molecular cloning of proteasome activator PA28-beta subunit of large yellow
      croaker (Pseudosciana crocea) and its coordinated up-regulation with MHC class I
      alpha-chain and beta 2-microglobulin in poly I:C-treated fish.
AB  - Antigenic peptides presented on MHC class I molecules to cytotoxic T-cells are
      generated in the cytosol by the 20S proteasome. Two activators PA28-alpha and
      PA28-beta, which are inducible by interferon-gamma (IFN-gamma), activate the
      latent 20S proteasome, thus playing an important role in the processing of MHC
      class I antigen. Molecular properties and function in the MHC class I antigen
      processing of PA28 have been well studied and documented in mammals while little
      is known in fish. In the present study, we reported the cloning of a PA28-beta
      gene homologue from the spleen of large yellow croaker (Pseudosciana crocea), an
      economically important marine fish (LycPA28-beta). The full-length cDNA of
      LycPA28-beta is 1133 nucleotides (nt) encoding a protein of 245 amino acids (aa),
      with a putative molecular weight of 27.7 kDa. The deduced protein shares 76, 69,
      61, 60, 59, 57 and 57% sequence identity to sequences found in zebrafish,
      flounder, pig, rat, mouse, cattle and human, respectively. The deduced LycPA28
      beta contains a PA28-beta subunit-specific insert in the region corresponding to
      the KEKE motif of the known PA28-alpha (Region B), a conserved activation loop
      (Region C) and a highly homologous C-terminal region among all three PA28
      subunits (Region E), and a characteristic proline-rich motif (Region A) and a
      potential protein kinase C recognition site (Region D). Western blot analysis of
      various tissues indicated that LycPA28-beta was constitutively expressed in
      kidney, liver, spleen and intestine, and weakly expressed in muscle tissue, but
      not detected in gills, heart and brain. The LycPA28-beta expression was
      significantly up-regulated in kidney, liver, spleen, intestine and muscle
      tissues, and also induced in gills after 72 h of treatment with a viral micmic,
      polyinosinic polycytidynic acid (poly I:C). The transcriptional analysis of
      LycPA28-beta and MHC class I alpha-chain (alpha-chain) and beta(2)-microglobulin
      (beta(2)m) in spleens of poly I:C-induced large yellow croaker was further
      performed by RT-PCR. The results showed that the expression of LycPA28-beta and
      class I alpha-chain and beta(2)m genes was coordinately up-regulated by poly I:C,
      suggesting that induction of the MHC class I antigen processing and presentation
      pathway may be required for the antiviral immune response triggered poly I:C in
      large yellow croaker.

PMID- 16901548
TI  - Relationship of CSF leukocytosis to compartmentalized changes in MCP-1/CCL2 in
      the CSF of HIV-infected patients undergoing interruption of antiretroviral
      therapy.
AB  - Although monocyte chemoattractant protein (MCP-1)/CCL2 is believed to mediate
      trafficking of HIV-activated leukocytes into the CNS, its role has not been
      studied directly in humans. To evaluate MCP-1's effects on CNS leukocyte
      infiltration, we measured CSF leukocytes and MCP-1 levels in serial plasma and
      cerebrospinal fluid (CSF) samples from subjects who experienced large increases
      in viral load after interrupting antiretrovirals. Following large increases in
      CSF MCP-1, CSF leukocytosis (15-166 cells/microL) developed in 4 of 6 subjects.
      Both initial MCP-1 levels and subsequent changes were 3-fold larger in CSF than
      plasma. The magnitude and timing of changes suggested that MCP-1 triggers the
      development of CSF pleocytosis.

PMID- 16901547
TI  - Depression and generalised anxiety in the general population in Belgium: a
      comparison between native and immigrant groups.
AB  - BACKGROUND: Knowledge of the mental health status of the general population in
      Belgium is limited. Only recently have prevalence rates and risk factors for
      depression and generalised anxiety been identified. However, the question remains
      whether there are statistically significant differences between foreign origin
      groups and the native population. METHODS: Basing our study on data from the
      Belgian Health Interview Survey 2001 and focusing on the adult population aged 18
      65 (N=7224), we consider eight risk factors for depression and generalised
      anxiety as assessed by the Symptom Checklist 90-subscales. The risk factors are
      region of origin, gender, age, household type, labour market position,
      educational level, household income and home ownership. Our approach involves
      weighted logistic regression. RESULTS: Analysis shows that most depressive
      symptoms are more prevalent among persons of Turkish or Moroccan origin than
      among Belgians or people from other EU Member States. This is not the case,
      though, for anxiety symptoms. However, if we consider depression and generalised
      anxiety as a syndrome, we find significantly more of the 10% highest SCL-scores
      in Turkish and Moroccan immigrants. Multivariate analysis indicates that their
      higher prevalence rate of anxiety is entirely attributable to their lower
      socioeconomic position. In the case of depression, the risk decreases only
      partly, leaving a significant association with Turkish or Moroccan origin.
      CONCLUSION: In Belgium, depression and generalised anxiety are more prevalent in
      the population originating from Turkey and Morocco than in population groups
      originating from within the European Union.

PMID- 16901549
TI  - Phenotypic characterization of autoreactive T cells in multiple sclerosis.
AB  - MS has been hypothesized to result from autoreactive T cell responses against
      myelin antigens. In this report, we examined myelin-specific CD8 and CD4 T cells
      for two markers differentially expressed on naive, memory and chronically
      stimulated T cells, CD28 and CD57. We observed differential expression on CD8 T
      cells in response to myelin antigens, but not in response to the recall antigen
      mumps. We demonstrate these cells display reduced proliferation and this may
      explain why therapies that limit the proliferation of T cells have had little
      effect on the course of MS, particularly later in the course of the disease.

PMID- 16901550
TI  - Effect of 1-deamino 8-D-arginine vasopressin spray on nasal cytology and
      mucociliary clearance in patients with nocturnal enuresis.
AB  - OBJECTIVE: To determine any possible adverse effect of 1-deamino 8-D-arginine
      vasopressin (DDAVP) spray on nasal cytology and mucociliary clearance in patients
      with nocturnal enuresis. METHODS: Twenty-two children aged 6-16 enrolled in the
      study. Epithelial surface cells samples were taken from the nasal mucosa and
      mucociliary clearance time was calculated before and 1 and 6 months after
      administration of DDAVP spray. RESULTS: No qualitative changes in the epithelial
      surface cells and mucociliary clearance time were observed at 1 and 6 months
      after therapy. CONCLUSION: Based on the findings of the present study, DDAVP
      spray can be used for 6 months in children without apparent risk of damage to the
      epithelial surface cells and mucociliary clearance time.

PMID- 16901551
TI  - Strategies for managing Type IV laryngotracheoesophageal clefts at Great Ormond
      Street Hospital for Children.
AB  - OBJECTIVE: To review our strategy for the treatment of patients with Type IV
      laryngotracheoesophageal cleft-a very rare congenital malformation. METHODS:
      Retrospective review of nine cases of Type IV laryngotracheoesophageal cleft
      managed between October 1994 and January 2004 at Great Ormond Street Hospital for
      Children, London. RESULTS: Three children were not operated upon (Group A)
      because of serious co-morbidity and parental decision not to opt for repair; they
      died at the ages of 2, 7 and 14 days, respectively. Six cases were repaired
      (Group B) at ages ranging from 2 to 53 days, all using an anterior cervico
      thoracic approach. Two cases were operated upon using conventional ventilation,
      three using cardiopulmonary bypass and one using extracorporeal membrane
      oxygenation. There was no intra-operative mortality. The number of operative and
      diagnostic procedures varied from 4 to 37. Two operated cases expired at the ages
      of 11 days and 25 months; both were operated upon using cardiopulmonary bypass
      and had significant cardiac co-morbidity. Post-operative microlaryngoscopy and
      bronchoscopy showed dehiscence in the cleft repair ranging from 1mm to 2cm in
      five cases. This was observed at the distal end in three patients and just below
      the vocal cords in two cases. Three cases underwent further repair which was
      successful. The most recent case repaired using extracorporeal membrane
      oxygenation required less heparin when compared with those done on
      cardiopulmonary bypass and had the best post-operative result. Two patients were
      finally decannulated. The total duration of diagnostic and operative procedures
      ranged from 9 to 26h and 30min. The hospital stay in the operated cases varied
      from 9 days to 2 years 2 months 3 days, and their ICU stay ranged from 9 days to
      10 months 7 days. All four of our patients with clefts which ended above the
      carina are alive after multiple repairs whereas all five cases with clefts
      extending all the way to the carina died (repair was attempted in two).
      CONCLUSION: Early diagnosis and repair are essential for successful treatment of
      Type IV laryngotracheoesophageal clefts. We believe it is best to repair this
      defect via an anterior cervico-thoracic approach, with or without a median
      sternotomy, and extracorporeal membrane oxygenation is now our preferred method
      of gas exchange during such repair. The longest Type IV clefts extending all the
      way to the carina have the worst prognosis. The decision to operate or not should
      be based upon the associated co-morbidity and fully informed parental choice,
      since treatment entails significant morbidity and mortality.

PMID- 16901552
TI  - Video otoscopy: bringing otoscopy out of the "black box".
AB  - BACKGROUND: Several billion dollars are spent each year on otitis media, a
      diagnosis for which educational approaches and diagnostic skills are suboptimal.
      The Center for Disease Control has identified improvement in otoscopy skills as a
      key intervention to curb inappropriate antibiotic usage. Educators are looking
      for interventions to both improve and assess otoscopy skills. Video otoscopy (VO)
      uses endoscopic technology to project the image of the ear onto a monitor for all
      to see, offering unexplored educational opportunity. The objective of this study
      is to perform an evaluation of VO systems in medical education from a review of
      the literature and hands-on experience of available technology. METHODS: The
      evaluation will focus on the technical acceptability (user requirements),
      clinical appropriateness (validity, reliability, feasibility), operational
      effectiveness (training requirements and implementation), and equipment
      selection. RESULTS: The technical requirements in pediatric education exceed
      those available in some VO systems, specifically pneumatic capability,
      sophisticated cameras and optics, and pediatric-sized ear speculums. VO images
      are comparable to the conventional otoscopic and otomicroscopic examinations. VO
      is feasible in a primary care setting and can be integrated into resident and
      medical student education. The technology in VO systems is changing rapidly,
      necessitating comparison of systems before equipment is purchased. CONCLUSIONS:
      VO is technically acceptable, clinically appropriate and can be integrated into
      the otoscopic education of residents and medical students. VO provides an
      opportunity to bring the pediatric ear examination out of the "black box,"
      potentially improving diagnostic skills, quality of care, and reducing antibiotic
      overuse.

PMID- 16901553
TI  - Inner ear dysplasia with agenesis of the corpus callosum.
AB  - In this case report we describe a patient with agenesis of the corpus callosum
      and asymmetric bilateral sensorineural hearing loss, who was found to have a
      bilateral inner ear dysplasia. Both of these anomalies have been associated with
      different members of the Pax gene family. However, to our knowledge this is the
      first report demonstrating the coexistence of these two unusual entities. By
      uncovering the inner ear malformation, we are able to better counsel this patient
      with regard to avoidance of high-risk activities such as contact sports and
      recommend prophylactic vaccination for meningitis prevention.

PMID- 16901554
TI  - Tympanoplasty in pediatric patients.
AB  - OBJECTIVE: The aim of this study is to analyze the clinical features and follow
      up of a series of pediatric patients with chronic otitis media undergoing
      tymponaplasty surgery and to identify the effect of the factors on the course.
      METHODS: Forty-one children (mean age 15.1+/-2.62 years, range from 8 to 16
      years) who had undergone tympanoplasty with or without ossicular reconstruction
      were evaluated. Age, gender, size and site of perforation, status of operated ear
      (dry/discharging), status of the contralateral ear, underlying cause of the
      perforations, surgical technique, preoperative and postoperative hearing levels,
      average postoperative follow-up time, and postoperative complications were
      recorded. RESULTS: Myringoplasty in 28 patients (68.3%), incus interposition in 7
      patients (17.1%), partial ossicular replacement prostheses in 4 patients (9.7%)
      and total ossicular replacement prostheses in 2 patients (4.9%) were performed.
      In the 37 (90.2%) of patients, intact graft was determined during postoperative
      follow-up. Surgical success including intact graft and postoperative air-bone gap
      of less than 25 dB were obtained in 34 (82.9%) cases. CONCLUSIONS: The present
      study suggested that tympanoplasty was a quite successful method in the
      appropriate pediatric patients between the ages of 8 and 16 years. In the
      preoperative evaluation for surgery success, some factors, such as dry middle
      ear, healthy contralateral ear and concordant to postoperative care should be
      considered.

PMID- 16901555
TI  - Development and validation of an improved RT-PCR assay with nested universal
      primers for detection of hepatitis E virus strains with significant sequence
      divergence.
AB  - Recent studies revealed that hepatitis E virus (HEV) genomes are more variable
      than previously thought and well-conserved regions suitable for designing
      universal primers are limited. In this study, based on alignment of 70 full
      length HEV sequences of genotypes 1-4, a part of the ORF2/ORF3 overlapping region
      was found to be the best target region for PCR amplification of various HEV
      strains. Using the newly designed primers, an RT-PCR method (ORF2/3-137 PCR) that
      amplifies a 137-nucleotide (nt) sequence within the ORF2/ORF3 overlapping region
      and is capable of amplifying all known HEV sequences was developed. When compared
      with the previous RT-PCR method (ORF2-457 PCR) that amplifies a 457 nt ORF2
      sequence, ORF2/3-137 PCR was two to three times more sensitive than ORF2-457 PCR
      upon testing serial dilutions of three HEV RNA-positive serum samples. The ORF2/3
      137 PCR assay could detect viraemia in five patients with acute or fulminant
      hepatitis E 3-14 days longer than ORF2-457 PCR after disease onset. All 41 ORF2
      457 PCR-positive serum samples of various genotypes tested positive for HEV RNA
      by the ORF2/3-137 PCR assay. Since the amplicons of ORF2/3-137 PCR contain
      variable sequences, a phylogenetic tree of the ORF2/3-137 products could clearly
      distinguish the different HEV genotypes.

PMID- 16901556
TI  - Diagnosis of Norovirus outbreaks by commercial ELISA or RT-PCR.
AB  - The IDEIA Norwalk-like virus (Dakocytomation Ltd., Ely, United Kingdom) and the
      Ridascreen Norwalk-like virus enzyme immunoassay (R-Biopharm AG, Darmstadt,
      Germany), were evaluated for the diagnosis of outbreaks of acute gastroenteritis.
      A panel of 158 fecal samples from 23 outbreaks, including confirmed rotavirus and
      astrovirus outbreaks, was used to determine the sensitivity and specificity of
      both ELISA kits relative to an RT-PCR protocol that was followed by Southern blot
      hybridization. Another panel consisted of 6 different genogroup I strains, 12
      genogroup II strains and 1 genogroup IV strain and was used to determine the
      scope of the tests. Compared to the RT-PCR, sensitivities of 38% and 36% and
      specificities of 96% and 88% were found for the Dako kit and the Ridascreen kit,
      respectively. Two genogroup I strains, and one genogroup II strain were not
      detected by the Dako kit, while five genogroup I and five genogroup II strains
      were not detected by the Ridascreen kit. The sensitivity of both ELISA kits, and
      the scope of the Ridascreen are considered disappointing. However, the ELISA kits
      can be useful for a preliminary screening, provided that ELISA negative outbreaks
      will be re-tested by RT-PCR methods.

PMID- 16901557
TI  - Learning-memory deficit with aging in APP transgenic mice of Alzheimer's disease
      and intervention by using tetrahydroxystilbene glucoside.
AB  - OBJECTIVE: To investigate learning-memory deficit in different ages of AD-like
      APP transgenic mice and to observe the protective effects of 2,3,5,4'
      tetrahydroxystilbene-2-O-beta-D-glucoside (TSG), which is the main component of
      Polygonum multiflorum, on learning-memory abilities. METHODS: PDAPPV717I
      transgenic (Tg) mice were randomly divided into 3 model groups (4, 10 and 16
      months old mice) and TSG treated (at doses 120 and 240 micromol/kg/d) groups. TSG
      was administered to some Tg mice with an age range 4-10 months. In untreated 10
      months old Tg mice, the TSG was administrated to those falling in the age range
      10-16 months. For the control group we adopted the same age and background
      C57BL/6J mice. The learning-memory ability was measured by applying Morris water
      maze (MWM) and object recognition test (ORT). RESULTS: In the 4 months old
      PDAPPV717I Tg mice, the learning-memory deficit was detected. The escape latency
      in MWM was prolonged, and the discrimination index decreased in ORT. In the 10
      months old Tg mice, the learning-memory deficit was aggravated. TSG improved all
      spatial learning-memory impairment in MWM as well as the object recognition
      impairment in ORT. In the 16 months old Tg mice, the learning-memory deficit
      remained to exist but abated a lot. TSG showed significant improvement in
      learning-memory ability in both MWM and ORT. CONCLUSION: PDAPPV717I transgenic
      mice with an age range 4-16 months revealed the existence of learning-memory
      deficit compared with the control group. Tetrahydroxystilbene glucoside not only
      prevents, i.e. at an early stage, the learning-memory deficit in AD-like model,
      but also can reverse the learning-memory deficit in the late stage of AD-like
      model. Thus, TSG could be considered among the future therapeutic drugs indicated
      for the treatment of AD.

PMID- 16901558
TI  - Negative selection using yeast cytosine deaminase/uracil phosphoribosyl
      transferase in Plasmodium falciparum for targeted gene deletion by double
      crossover recombination.

PMID- 16901559
TI  - Congestive heart failure-related anemia and a role for erythropoietin.
AB  - Congestive heart failure (CHF) is a common clinical problem, especially affecting
      the elderly. Current strategies of neurohormonal blockade with medications like
      angiotensin converting enzyme inhibitors have improved morbidity and mortality,
      but further improvement in outcomes requires new strategies. Both anemia and
      chronic renal disease commonly accompany congestive heart failure; their close
      relationship, in which one disease exacerbates the other, has been termed the
      cardio-renal-anemia syndrome. Correction of anemia in CHF patients using
      recombinant erythropoietin is feasible; small studies suggest that anemic
      congestive heart failure patients may have improved morbidity with this therapy.
      Recent animal and human studies of erythropoietin have shown that its benefit may
      be derived from both hematological and newly discovered non-hematological
      properties. Anemia might soon be considered a modifiable risk factor for optimal
      CHF management.

PMID- 16901560
TI  - "The attack of the 52 cm lead": an unusual case of late cardiac perforation by a
      passive-fixation permanent pacemaker lead.
AB  - We report a case of right ventricular perforation by a passive-tined permanent
      pacemaker lead detected 1 month after implantation. The pacemaker lead was seen
      to perforate through the myocardium and pericardium and moving freely in the
      mediastinum with no evidence of pericardial effusion. Extraction was uneventful.

PMID- 16901561
TI  - Left ventricular free wall rupture in takotsubo cardiomyopathy.

PMID- 16901563
TI  - Happy 25th birthday to the International Journal of Cardiology.

PMID- 16901562
TI  - The prognostic significance of restrictive diastolic filling associated with
      heart failure: a meta-analysis.
AB  - BACKGROUND: Several studies have reported that the presence of a restrictive
      filling pattern (RFP) is associated with poor outcome in patients with heart
      failure (HF). These studies, of variable sample size, have involved different HF
      patient groups with variable associated mortality rates and follow-up times, and
      while powered for effects on combined end-points such as death or hospital
      admission, many were underpowered to reliably determine the overall effect of the
      RFP on total mortality. Consequently, we performed a meta-analysis to determine
      the mortality associated with RFP in patients with HF. METHODS: We searched
      several online medical databases for prospective studies of patients with HF. All
      authors were requested to confirm their data. All-cause mortality was compared
      between RFP and non-restrictive filling patterns (Non-RFP). Review Manager
      version 4.2.7 software was used for the analysis. RESULTS: 3024 patients in 27
      studies were identified (379 idiopathic cardiomyopathy, 2645 mixed aetiology HF).
      Average follow-up was between 3 months and 5 years. 1284 (42%) patients had RFP
      at baseline. 688 deaths occurred and the overall odds ratio for death was 4.36
      (CI 3.60, 5.04); idiopathic group: 6.65 (CI 3.86, 11.47); mixed aetiology group:
      4.10 (CI 3.34, 5.04). The overall odds ratio for death/transplantation was 4.87
      (CI 4.04, 5.86); idiopathic group: 7.62 (CI 4.50, 12.92); mixed aetiology group:
      4.56 (CI 3.74, 5.56). CONCLUSIONS: Restrictive filling pattern is associated with
      a four-fold increase in mortality in patients with HF and thus should be an
      important part of the echocardiographic assessment of such patients.

PMID- 16901564
TI  - D-dimer local expression is increased in symptomatic patients undergoing carotid
      endarterectomy.
AB  - BACKGROUND: Although atherosclerosis is a silent widespread disease, the focal
      character of the lesions triggering the clinical manifestations is
      unquestionable. We hypothesized that symptomatic patients with advanced, unstable
      carotid plaques have increased local intraplaque and circulating levels of fibrin
      fibrinogen related products. METHODS: Plaque tissue and plasma samples were
      studied in 106 patients undergoing endarterectomy for symptomatic and
      asymptomatic carotid disease. Fibrin-fibrinogen related products were evaluated
      by ELISA, Western-blotting, and histology. All tested parameters were compared
      with patient carotid symptomatology, multiple vascular risk factors (VRF),
      bilateral carotid pathology, ultrasound examination, and previous therapies with
      statins and/or antiplatelet drugs. RESULTS: In symptomatic patients, plasma D
      dimer was elevated in patients with unstable carotid plaques (UNS) compared with
      stable (STA) ones (857+/-121 vs. 692+/-156 ng/ml, p=0. 026). Furthermore, plasma
      D-dimer was significantly increased in patients with a coexistence of carotid and
      coronary artery disease, compared to others (976+/-325 vs. 714+/-197 ng/ml;
      p<0.001). Intra-plaque D-dimer content was increased in ulcerated-complicated
      (UC) plaques compared with fibrous non-complicated (F) plaques in symptomatic
      patients (5.9+/-1 vs. 1.8+/-1, p<0.001), and in patients with
      hypercholesterolaemia, compared with those with normal cholesterol levels (6.1+/
      1 vs. 2.9+/-0.7; p=0.027). However, there was no correlation between D-dimer
      content in the carotid plaque and plasma D-dimer levels. CONCLUSIONS:
      Hypercholesterolemia and UC plaques appear to be associated with high fibrin
      intraplaque turnover as demonstrated by higher intraplaque D-dimer. Plasma
      markers of fibrin turnover were increased in UNS plaques, and in patients with
      coexisting carotid and coronary artery disease. Although, both plasma and plaque
      D-dimers were associated with unstable carotid disease, the usefulness of the
      measurement of plasma D-dimer in these patients should be confirmed by
      prospective studies.

PMID- 16901565
TI  - Handmaiden or right-hand man: is the relationship between doctors and nurses
      still therapeutic?

PMID- 16901566
TI  - Alteration in sensitivity of ionotropic glutamate receptors and tachykinin
      receptors in spinal cord contribute to development and maintenance of nerve
      injury-evoked neuropathic pain.
AB  - Allodynia or hyperalgesia induced by peripheral nerve injury may be involved in
      changes in the sensitivity of neurotransmitters at the spinal cord level. In
      order to clarify the functional role of neurotransmitters in peripheral nerve
      injury, we used rats with nerve injury induced by chronic constriction of the
      sciatic nerve (CCI rat model) and estimated the effects of the intrathecal
      injection of drugs known to affect glutamate and tachykinin receptors. In sham
      operated rats, the NMDA receptor agonist NMDA and AMPA-kinate receptor agonist RS
      (5)-bromowillardin reduced withdrawal latency. The non-competitive NMDA receptor
      antagonist MK-801, competitive NMDA receptor antagonist AP-5 and AMPA-kinate
      receptor antagonist NBQX increased withdrawal latency. Substance P (SP) increased
      the withdrawal latency but only transitorily. The NK1 receptor antagonist RP67580
      increased withdrawal latency, but the NK2 receptor antagonist SR48968 did not
      show an effect. In CCI rats, RS-(5)-bromowillardin reduced withdrawal latency,
      but NMDA did not show an effect. NBQX increased withdrawal latency, while MK-801
      and AP-5 showed little or no effect. SP reduced withdrawal latency, and both
      RP67580 and SR48968 increased it. These results indicate that the alteration in
      sensitivity of ionotropic glutamate receptors and tachykinin receptors in the
      spinal cord contribute to development and maintenance of nerve injury-evoked
      neuropathic pain.

PMID- 16901567
TI  - Substrate and positional specificity of feruloyl esterases for monoferuloylated
      and monoacetylated 4-nitrophenyl glycosides.
AB  - 4-Nitrophenyl glycosides of 2-, 3-, and 5-O-(E)-feruloyl- and 2- and 5-O-acetyl
      alpha-L-arabinofuranosides and of 2-, 3-, and 4-O-(E)-feruloyl- and 2-, 3- and 4
      O-acetyl-beta-D-xylopyranosides, compounds mimicking natural substrates, were
      used to investigate substrate and positional specificity of type-A, -B, and -C
      feruloyl esterases. All the feruloyl esterases behave as true feruloyl esterases
      showing negligible activity on sugar acetates. Type-A enzymes, represented by
      AnFaeA from Aspergillus niger and FoFaeII from Fusarium oxysporum, are
      specialized for deferuloylation of primary hydroxyl groups, with a very strong
      preference for hydrolyzing 5-O-feruloyl-alpha-L-arabinofuranoside. On the
      contrary, type-B and -C feruloyl esterases, represented by FoFaeI from F.
      oxysporum and TsFaeC from Talaromyces stipitatus, acted on almost all ferulates
      with exception of 4- and 3-O-feruloyl-beta-D-xylopyranoside. 5-O-Feruloyl-alpha-L
      arabinofuranoside was the best substrate for both TsFaeC and FoFaeI, although
      catalytic efficiency of the latter enzyme toward 2-O-feruloyl-alpha-L
      arabinofuranoside was comparable. In comparison with acetates, the corresponding
      ferulates served as poor substrates for the carbohydrate esterase family 1
      feruloyl esterase from Aspergillus oryzae. The enzyme hydrolyzed all alpha-L
      arabinofuranoside and beta-D-xylopyranoside acetates. It behaved as a non
      specific acetyl esterase rather than a feruloyl esterase, with a preference for 2
      O-acetyl-beta-D-xylopyranoside.

PMID- 16901568
TI  - A simplified QTL mapping approach for screening and mapping of novel AFLP markers
      associated with beef marbling.
AB  - Genome screening of quantitative trait loci (QTL) for a complex trait is usually
      costly and highly laborious, as it requires a large number of markers spanning
      the whole genome. Here we present a simplified approach for screening and mapping
      of QTL-linked markers for beef marbling using a WagyuxLimousin F(2) reference
      population. This simplified approach involves integration of the amplified
      fragment length polymorphism (AFLP) with DNA pooling and selective genotyping and
      comparative bioinformatics tools. AFLP analysis on two high and two low marbling
      DNA pools yielded ten visually different markers. Among them, four were confirmed
      based on individual AFLP validation. Sequencing and in silico characterization
      assigned two of these AFLP markers to bovine chromosomes 1 (BTA1) and 13 (BTA13),
      which are orthologous to human chromosomes HSA21q22.2 and HSA10p11.23 with both
      regions harboring QTL for obesity-related phenotypes. Both AFLP markers showed
      significantly large additive genetic effects (0.28+/-0.11 on BTA1 and 0.54+/-0.21
      on BTA13) on beef-marbling score (BMS) (P<0.05). Overall, this approach is less
      time consuming, inexpensive and in particular, suitable for screening and mapping
      QTL-linked markers when targeting one or a few complex traits.

PMID- 16901569
TI  - Comparative in vivo mucoadhesion studies of thiomer formulations using magnetic
      resonance imaging and fluorescence detection.
AB  - The aim of this study was to compare different oral delivery systems based on the
      thiolated polymer polycarbophil-cysteine (PCP-Cys) and to provide evidence for
      the validity of the hypothesis that unhydrated polymers provide better
      mucoadhesion in vivo. To achieve dry polymer application, a new, experimental
      dosage form named Eutex (made of Eudragit L100-55 and latex) capsule has been
      developed. Magnetic resonance imaging was used to localize the point of release
      of the thiolated polymer from the application forms via the positive magnetic
      resonance signal from a gadolinium complex (Gd-DTPA). In vivo mucoadhesion was
      determined by ascertaining the residence time of the fluorescence-tagged thiomer
      on intestinal mucosa after 3 h. Results showed that in comparison to conventional
      application forms the Eutex capsules led to 1.9-fold higher mucoadhesive
      properties of PCP-Cys when compared to application with a conventional enteric
      coated capsule, and to 1.4-fold higher mucoadhesion when compared to
      administration with an enteric-coated tablet of the thiomer. The findings of this
      study should contribute to the understanding of mucoadhesion and mucoadhesion
      influencing parameters in vivo and should therefore be of considerable interest
      for the development of future mucoadhesive oral drug delivery dosage forms.

PMID- 16901570
TI  - Targeted gene delivery with trisaccharide-substituted chitosan oligomers in vitro
      and after lung administration in vivo.
AB  - The aim of this study was to improve the gene delivery efficacy of chitosan
      oligomer polyplexes by introducing a trisaccharide branch that targets cell
      surface lectins. For this purpose, chitosan oligomers were substituted by a
      trisaccharide with the N-acetylglucosamine residue at the free end, and the
      ability of the trisaccharide-substituted chitosan oligomers (TCO) polyplexes to
      transfect various cell lines in vitro and lung tissue after in vivo
      administration to mice was investigated. Live-cell confocal microscopy showed
      improved cellular uptake in HEK 293 cells (11-fold, p<0.001) for the TCO
      polyplexes compared with the linear chitosan oligomers. Colloidal stability was
      also enhanced with the substituted form, which suggests that the trisaccharide
      branch stabilised the polyplexes by means of a steric stabilisation mechanism.
      Interestingly, gene expression levels in the human liver hepatocyte (HepG2) cells
      were 10-fold higher with the TCO polyplexes than those mediated by
      polyethyleneimine. A similar improvement was obtained in a human bronchial
      epithelial cell line (16HBE14o-). Transfection with the TCO was significantly
      inhibited (by 30-80%), for all the cell lines tested, in the presence of the free
      trisaccharide branch, confirming lectin-mediated uptake. Finally, in vivo studies
      showed that, 24 h after lung administration to mice, luciferase gene expression
      was 4-fold higher with the TCO than with the corresponding linear chitosan
      oligomers.

PMID- 16901572
TI  - Turning on the off switch: regulation of anti-viral T cell responses in the liver
      by the PD-1/PD-L1 pathway.

PMID- 16901573
TI  - Autoimmune hepatitis in the elderly: what is the difference?

PMID- 16901574
TI  - Diagnosis of cholangiocarcinoma in patients with PSC: a sight on cytology.

PMID- 16901576
TI  - Insulin resistance and HCV: will new knowledge modify clinical management?

PMID- 16901577
TI  - Endpoints for clinical trials on treatment of hepatitis C.

PMID- 16901578
TI  - The extrahepatic contribution to HCV plasma viremia.

PMID- 16901579
TI  - Transmission of hepatitis C virus by blood transfusions and other medical
      procedures: a global review.
AB  - Hepatitis C virus (HCV) is a leading cause of chronic blood-borne infection and
      chronic liver disease. The global epidemic of HCV infection emerged in the second
      half of the 20th century, and several lines of evidence indicate that it was
      primarily triggered and fed iatrogenically by the increasing use of parenteral
      therapies and blood transfusion. In developed countries, the rapid improvement of
      healthcare conditions and the introduction of anti-HCV screening for blood donors
      have led to a sharp decrease in the incidence of iatrogenic hepatitis C, but the
      epidemic continues to spread in developing countries, where the virus is still
      transmitted through unscreened blood transfusions and non-sterile injections.
      This article reviews the published literature concerning HCV transmission through
      blood transfusions and other unsafe medical procedures. Given the substantial
      difference in current disease transmission patterns between the northern and
      southern hemispheres, the situation in developed and developing countries is
      separately analysed.

PMID- 16901580
TI  - Emergent neutrality.
AB  - Community ecology is in a current state of creative ferment, stimulated by the
      development of neutral models of community organization. Here, I reflect on
      recent papers by Scheffer and van Nes, and by Gravel et al., which illuminate how
      neutrality can emerge from ecological and evolutionary processes, thus suggesting
      ways to unify neutral and niche perspectives.

PMID- 16901581
TI  - Bioturbation: a fresh look at Darwin's last idea.
AB  - Bioturbation refers to the biological reworking of soils and sediments, and its
      importance for soil processes and geomorphology was first realised by Charles
      Darwin, who devoted his last scientific book to the subject. Here, we review some
      new insights into the evolutionary and ecological role of bioturbation that would
      have probably amazed Darwin. In modern ecological theory, bioturbation is now
      recognised as an archetypal example of 'ecosystem engineering', modifying
      geochemical gradients, redistributing food resources, viruses, bacteria, resting
      stages and eggs. From an evolutionary perspective, recent investigations provide
      evidence that bioturbation had a key role in the evolution of metazoan life at
      the end of the Precambrian Era.

PMID- 16901583
TI  - Silymarin synthesis and degradation by peroxidases of cell suspension cultures of
      Silybum marianum.
AB  - Treatment of Silybum marianum cell cultures with methyl jasmonate elicits the
      production of the antihepatotoxic drug silymarin and its release into the culture
      medium. In this work, we investigated the involvement of peroxidases (EC
      1.11.1.7; donor hydrogen peroxidase oxido-reductase) in silymarin turnover in
      cell cultures as well as the influence of elicitation on the activity towards
      several substrates. Peroxidases from cell extracts and, to a higher degree from
      the spent medium, used the silymarin precursors taxifolin and coniferyl alcohol
      as substrates. Silymarin compounds were also degraded by suspension culture
      peroxidases; however, the oxidation efficiency was not modified by elicitation.
      S. marianum peroxidases were able to catalyse the oxidative coupling of taxifolin
      and coniferyl alcohol to silybinins. The synthetic activity was mainly associated
      with the extracellular compartment and as before, methyl jasmonate did not modify
      oxidative coupling activity. Changes in the isoenzyme profiles were not observed
      in elicited cultures.

PMID- 16901582
TI  - Effect of low temperature on ethanolic fermentation in rice seedlings.
AB  - Rice seedlings (Oryza sativa L.) were incubated at 5-30 degrees C for 48 h and
      the effect of temperature on ethanolic fermentation in the seedlings was
      investigated in terms of low-temperature adaptation. Activities of alcohol
      dehydrogenase (ADH, EC 1.1.1.1) and pyruvate decarboxylase (PDC, EC 4.1.1.1) in
      roots and shoots of the seedlings were low at temperatures of 20-30 degrees C,
      whereas temperatures of 5, 7.5 and 10 degrees C significantly increased ADH and
      PDC activities in the roots and shoots. Temperatures of 5-10 degrees C also
      increased ethanol concentrations in the roots and shoots. The ethanol
      concentrations in the roots and shoots at 7.5 degrees C were 16- and 12-times
      greater than those in the roots and shoots at 25 degrees C, respectively. These
      results indicate that low temperatures (5-10 degrees C) induced ethanolic
      fermentation in the roots and shoots of the seedlings. Ethanol is known to
      prevent lipid degradation in plant membrane, and increased membrane-lipid
      fluidization. In addition, an ADH inhibitor, 4-methylpyrazole, decreased low
      temperature tolerance in roots and shoots of rice seedlings and this reduction in
      the tolerance was recovered by exogenous applied ethanol. Therefore, production
      of ethanol by ethanolic fermentation may lead to low-temperature adaptation in
      rice plants by altering the physical properties of membrane lipids.

PMID- 16901584
TI  - Relations between tocopherol, chlorophyll and lipid peroxides contents in shoots
      of Ni-treated wheat.
AB  - The influence of 50 and 100 microM Ni on chlorophyll and tocopherol contents, as
      well as lipid peroxidation was studied in the shoots of wheat plants. Chlorophyll
      content in the shoots decreased in response to Ni application. Ni stress led to
      an enhancement of lipid peroxides content, accompanied by a substantial increase
      in tocopherol concentration in the wheat shoots.

PMID- 16901585
TI  - Internalization and recycling properties of neurotensin receptors.
AB  - The targeting, internalization and recycling of membrane receptors in response to
      extracellular ligands involve a series of molecular mechanisms which are
      beginning to be better understood. The receptor-dependent internalization of
      neurotensin has been widely investigated using endogenous or heterologous
      receptor expression systems. This review focuses on the general properties of
      neurotensin sequestration and on the characterization of the receptors involved
      in this process.

PMID- 16901586
TI  - Functional domains of the subtype 1 neurotensin receptor (NTS1).
AB  - The subtype 1 neurotensin receptor (NTS1) belongs to the family of G protein
      coupled receptors with seven transmembrane domains and mediates most of the known
      effects of neurotensin. In the past years, mutagenesis studies have allowed to
      delineate functional regions of the receptor involved in agonist and antagonist
      binding, G protein coupling, sodium sensitivity of agonist binding, and agonist
      induced receptor internalization. These data are reviewed and discussed in the
      present paper.

PMID- 16901587
TI  - Abnormal modulation of cholinergic neurotransmission by endomorphin 1 and
      endomorphin 2 in isolated bronchus of type 1 diabetic rats.
AB  - To assess whether diabetes alters the regulatory effects of mu-opioid receptor
      (MOR) agonists on the cholinergic bronchoconstriction, we investigated the
      inhibitory effects of endomorphins (EMs) on the electrical field stimulation
      (EFS)-induced cholinergic bronchoconstriction in type 1 diabetic rats. At 4 weeks
      after the onset of diabetes, both the EFS- and exogenous acetylcholine (ACh)
      induced bronchoconstriction in diabetes in vitro were greater than those in non
      diabetes rats. Furthermore, endomorphin 1 (EM1) and endomorphin 2 (EM2) inhibited
      the response to EFS in diabetic rat isolated bronchus in a concentration- and
      frequency-dependent manner, which is in agreement with that in non-diabetes.
      However, the inhibitory effects of EMs on the EFS-induced bronchoconstriction in
      diabetes were significantly weaker than those in non-diabetes. Both EM1 and EM2
      (1 microM) had no effect on the contractile response to exogenous ACh, indicating
      a prejunctional effect. Furthermore, the inhibitory effect on the EFS-induced
      bronchoconstriction was blocked by naloxone (10 microM). Eight weeks after the
      induction of diabetes, both the EFS- and exogenous ACh-induced
      bronchoconstrictions in diabetes were further enhanced compared to those in short
      time (4 weeks) diabetic rats. Moreover, the inhibitory effects of EMs on the EFS
      induced bronchoconstriction were further attenuated. These results suggest that
      dysfunction of presynaptic inhibitory modulation through opioid receptor by EMs
      may take place in the bronchus of diabetic rats.

PMID- 16901588
TI  - Exocytotic release of dopamine in ventral tegmental area slices from C57BL/6 and
      dopamine transporter knockout mice.
AB  - The present study used voltammetry to ascertain whether electrically stimulated
      somatodendritic dopamine release in ventral tegmental area slices from C57BL/6
      and dopamine transporter knockout mice was due to exocytosis or dopamine
      transporter reversal, as has been debated. The maximal concentration of
      electrically evoked dopamine release was similar between ventral tegmental area
      slices from dopamine transporter knockout and C57BL/6 mice. Dopamine transporter
      blockade (10 microM nomifensine) in slices from C57BL/6 mice inhibited dopamine
      uptake but did not alter peak evoked dopamine release. In addition, dopamine
      release and uptake kinetics in ventral tegmental area slices from dopamine
      transporter knockout mice were unaltered by the norepinephrine transporter
      inhibitor, desipramine (10 microM), or the serotonin transporter inhibitor,
      fluoxetine (10 microM). Furthermore, maximal dopamine release in ventral
      tegmental area slices from both C57BL/6 and dopamine transporter knockout mice
      was significantly decreased in response to Na(+) channel blockade by 1 microM
      tetrototoxin, removal of Ca(2+) from the perfusion media and neuronal vesicular
      monoamine transporter inhibition by RO-04-1284 (10 microM) or tetrabenazine (10
      and 100 microM). Finally, the glutamate receptor antagonists AP-5 (50 and 100
      microM) and CNQX (20 and 50 microM) had no effect on peak somatodendritic
      dopamine release in C57BL/6 mice. Overall, these data suggest that similar
      mechanisms, consistent with exocytosis, govern electrically evoked dopamine
      release in ventral tegmental area slices from C57BL/6 and dopamine transporter
      knockout mice.

PMID- 16901589
TI  - Impairment of GABAergic neurotransmitter system in the amygdala of young rats
      after 4-week zinc deprivation.
AB  - On the basis of the evidence that the excitability of hippocampal glutamatergic
      neurotransmitter system is enhanced by dietary zinc deficiency, the response of
      amygdalar neurotransmitter system was checked in young rats fed a zinc-deficient
      diet for 4 weeks. Extracellular zinc concentration in the amygdala, which was
      measured by the in vivo microdialysis, was almost the same as that in the
      hippocampus and decreased by zinc deficiency. Extracellular zinc concentration in
      the amygdala was increased both in the control and zinc-deficient rats by
      stimulation with 100mM KCl, suggesting that the increase in extracellular zinc in
      the amygdala, as well as that in the hippocampus, is linked with neuronal
      depolarization. In amygdalar extracellular fluid, the basal glutamate
      concentration was not significantly different between the control and zinc
      deficient rats and was increased to almost the same extent between them by
      stimulation with 100mM KCl, unlike more increase in extracellular glutamate
      concentration in the hippocampus in zinc deficiency. On the other hand, the basal
      GABA concentration in the amygdalar extracellular fluid was significantly lower
      in zinc-deficient rats and was not increased both in the control and zinc
      deficient rats by stimulation with 100mM KCl. These results suggest that
      GABAergic neurotransmitter system is critically impaired in the amygdala of young
      rats after 4-week zinc deprivation.

PMID- 16901590
TI  - The genetic immunization with paraflagellar rod protein-2 fused to the HSP70
      confers protection against late Trypanosoma cruzi infection.
AB  - The immunological properties of the Trypanosoma cruzi paraflagellar rod proteins
      (PFR2 and PFR3) administered alone as well as fused to HSP70 have been analyzed
      in mice in the context of genetic immunization. The immunization of mice with the
      DNA vectors containing the PFRs gene or PFRs-HSP70 fused genes induced high level
      of IgG(2a) anti-PFRs. However, only the immunization with the PFR2-HSP70 fused
      genes triggers in spleen cells a statistically significant enhancement of
      expression of IL-12 and IFN-gamma and a decrease in the percentage of cells
      expressing IL-4. Likewise, the PFR2-HSP70 molecule elicits a statistically
      significant activation of PFR2 antigen specific CTLs. Immunization with the PFR2
      HSP70 chimeric gene provided a protective response against a T. cruzi
      experimental infection.

PMID- 16901591
TI  - Active surveillance of Streptococcus pneumoniae bacteremia in Italian children.
AB  - There are few data published regarding the incidence of Streptococcus pneumoniae
      bacteremia in Italian children. A 14-month surveillance study was conducted in 10
      paediatric hospitals to investigate the rate of Sp bacteremia in children aged
      less than 5 years. The serotype prevalence and antimicrobial susceptibility of
      isolates were determined. A total of 55 Sp isolates were obtained from 4576 blood
      cultures (incidence rate, 1.2%). In order of frequency, the most common serotypes
      were 14, 23F, 19F, 9V, 1. Serotypes in the 7-valent conjugate pneumococcal
      vaccine (4, 6B, 9V, 14, 18C, 19F, 23F) accounted for 70% of isolates under 2
      years of age, and 58% in the interval between 2 and 5 years of age.

PMID- 16901592
TI  - Demonstration of loss of attenuation and extended field persistence of a live
      avian metapneumovirus vaccine.
AB  - A live A type avian metapneumovirus (AMPV) vaccine which had been shown to be
      highly protective and short lived in experimental conditions was found to persist
      for longer periods in the field and to be associated with disease. Previously
      other factors such as possible secondary pathogens and management considerations
      had made it impossible to conclude whether the observed disease was a result of
      an increase in the vaccine virulence. In this study, an AMPV was isolated from
      poults on a farm which had been vaccinated with the same live A type vaccine.
      Full sequencing of the isolate, the vaccine and the vaccine progenitor confirmed
      its vaccine origin and further showed that generation of the vaccine had only
      involved nine substitutions of which three coded for amino acid changes. The
      isolated virus was inoculated into 1-day-old turkey poults in disease secure
      isolators and shown to cause disease with a severity similar to that caused by
      virulent field virus. Only two coding mutations were associated with this
      reversion to virulence.

PMID- 16901593
TI  - The virosomal influenza vaccine Invivac: immunogenicity and tolerability compared
      to an adjuvanted influenza vaccine (Fluad in elderly subjects.
AB  - Several approaches are currently being pursued in order to improve the efficacy
      of influenza vaccines in elderly individuals and others who have impaired immune
      responses to conventional influenza vaccines. There are two influenza vaccines
      available for elderly subjects: Fluad (Chiron) and Invivac (Solvay
      Pharmaceuticals). The present clinical study was a randomized, endpoint-blind,
      parallel group study in elderly subjects aged 61 years and older to investigate
      the safety and immunogenicity of these vaccines as compared to a standard
      influenza vaccine Invivac (Solvay Pharmaceuticals). The three vaccines had
      similar immunogenicity results, whereas the tolerability profile of Invivac was
      better as compared to Fluad.

PMID- 16901594
TI  - The use of Markov chain Monte Carlo uncertainty analysis to support a Public
      Health Goal for perchloroethylene.
AB  - The current Public Health Goal (PHG) for perchloroethylene (PCE) was derived
      using upper-bound estimates of fractional PCE metabolism in humans. These
      estimates were in part obtained from a published evaluation of the uncertainty
      and variability in human PCE metabolism conducted using a physiologically-based
      pharmacokinetic (PBPK) model in a Markov chain Monte Carlo (MCMC) analysis;
      however, the data used in that analysis were limited to post-exposure PCE blood
      and exhaled air concentrations from a single study. A more recent study [Volkel,
      W., Friedewald, M., Lederer, E., Pahler, A., Parker, J., Dekant, W., 1998.
      Biotransformation of perchloroethene: dose-dependent excretion of trichloroacetic
      acid, dichloroacetic acid, and N-acetyl-S-(trichlorovinyl)-l-cysteine in rats and
      humans after inhalation. Toxicol. Appl. Pharmacol. 153(1), 20-27.] provides data
      on blood concentrations of PCE and its major metabolite, trichloroacetic acid
      (TCA), and urinary excretion of TCA following exposure of human subjects to lower
      concentrations of PCE (10-40ppm) than in previous studies. In the present effort,
      a new MCMC analysis was performed that focused on data from this study along with
      two others [Fernandez, J., Guberan, E., Caperos, J., 1976. Experimental human
      exposures to tetrachloroethylene vapor and elimination in breath after
      inhalation. Am. Ind. Hyg. Assoc. J. 37, 143-150; Monster, A., Boersma, G.,
      Steenweg, H., 1979. Kinetics of tetrachloroethylene in volunteers; influence of
      exposure concentration and work load. Int. Arch. Occup. Environ. Health 42, 303
      309.] providing data on PCE blood concentrations and urinary excretion of TCA. To
      provide an accurate prediction of TCA kinetics, the PBPK model used here includes
      a description of the metabolism of PCE to TCA in both the liver and kidney. The
      resulting upper 95th percentile estimates of fraction of PCE metabolized by
      inhalation and oral routes were 2.1 and 5.2%, respectively, compared to 58 and
      79% used in the derivation of the PHG.

PMID- 16901595
TI  - Risk assessment for carnitine.
AB  - Carnitine is a conditionally essential amino acid-like compound involved in the
      transport of long-chain fatty acids into the mitochondria during the beta
      oxidation process. Carnitine has become an increasingly popular ingredient in
      dietary supplements, especially weight loss and some sports nutrition products. A
      number of clinical trials have been conducted examining the effect of carnitine
      supplementation on weight loss and energy balance. Regarding safety, systematic
      evaluation of the research designs and data do not provide a basis for risk
      assessment and the usual safe upper level of intake (UL) derived from it unless
      the newer methods described as the observed safe level (OSL) or highest observed
      intake (HOI) are utilized. The OSL risk assessment method indicates that the
      evidence of safety is strong at intakes up to 2000mg/day l-carnitine equivalents
      for chronic supplementation, and this level is identified as the OSL. Although
      much higher levels have been tested without adverse effects and may be safe, the
      data for intakes above 2000mg/day are not sufficient for a confident conclusion
      of long-term safety.

PMID- 16901596
TI  - 'Rakter dosh'--corrupting blood: The challenges of preventing thalassemia in
      Bengal, India.
AB  - Thalassemia is an inherited blood disorder that has been receiving increasing
      attention in India. However, prevention of thalassemia in India continues to be
      difficult despite efforts of public health professionals and the government.
      Using West Bengal as a case study, this paper attempts to unravel some of the
      barriers to the prevention campaign and the consequent under utilization of the
      program. Lack of access, low awareness, low-risk perception and poverty are all
      important proximate constraints; however, one of the greatest barriers to the
      program is rooted in cultural notions of blood, marriage, identity, personhood
      and kinship in Bengali society. Blood is so deeply valued in the Bengali kinship
      system that this genetic mutation is perceived to be corrupting the blood (rakter
      dosh). Being a thalassemia carrier (i.e., having thalassemia minor) renders an
      individual unfit as a suitable marriage partner because of beliefs related to
      purity of blood, its association with the continuity of the lineage, and
      subsequent transmission of desirable traits to future generations. The risk of
      non-marriage affects women disproportionately, and parents are not inclined to
      test their daughters because of the possibility of not being able to marry them
      off to eligible suitors. The stigma associated with having thalassemia minor
      (TMI) is a deterrent to the disclosure of thalassemia status as well as to
      testing. Using anthropological theories and ethnographic methods, this paper
      focuses on the gendered process by which the diagnosis of a thalassemia carrier
      'spoils' identities, thereby creating a disjuncture between the goals of the
      prevention program and people's need for social conformity, and ultimately
      between medical desirability and social desirability. The paper also suggests
      policies for enhancing the utilization of the program. Finally the conclusions
      from this study have potential applications for public health prevention programs
      that confront problems of stigma in program acceptability.

PMID- 16901597
TI  - Visual field x response hand interactions and level priming in the processing of
      laterally presented hierarchical stimuli.
AB  - Hemisphere-specific processing of laterally presented global and local stimulus
      levels was investigated by (a) examining interactions between the visual field of
      stimulus presentation and the response hand and (b) comparing intra- with inter
      hemispheric effects of level priming (i.e. faster and more accurate performance
      when the target level repeats). Although in Experiment 1, which involved two
      choice responses with left and right hands, performance costs occurred when the
      same hemisphere received the stimulus and controlled the response hand, further
      analyses suggest that these effects reflect spatial compatibility rather than
      intra-hemispheric interference. Consistent with the spatial compatibility
      interpretation, in Experiment 2 a similar visual field x response interaction was
      obtained with regard to left and right responses given with the same hand. Trial
      to-trial level priming occurred in both experiments and was unaffected by the
      intra-hemispheric sequence of target levels. Implications regarding hemispheric
      processing mode are discussed.

PMID- 16901598
TI  - Alterations of muscarinic and GABA receptor binding in the posterior cingulate
      cortex in schizophrenia.
AB  - The posterior cingulate cortex (PCC), a key component of the limbic system, has
      been implicated in the pathology of schizophrenia because of its sensitivity to
      NMDA receptor antagonists. Recent studies have shown that the PCC is
      dysfunctional in schizophrenia, and it is now suspected to be critically involved
      in the pathogenesis of schizophrenia. Studies also suggest that there are
      abnormalities in muscarinic and GABAergic neurotransmission in schizophrenia.
      Therefore, in the present study we used quantitative autoradiography to
      investigate the binding of [(3)H]pirenzepine, [(3)H]AF-DX 384 and [(3)H]muscimol,
      which respectively label M1/4 and M2/4 muscarinic and GABA(A) receptors, in the
      PCC of schizophrenia and control subjects matched for age and post-mortem
      interval. The present study found that [(3)H]pirenzepine binding was
      significantly decreased in the superficial (-24%, p=0.002) and deep (-35%,
      p<0.001) layers of the PCC in the schizophrenia group as compared with the
      control group. In contrast, a dramatic increase in [(3)H]muscimol binding was
      observed in the superficial (+112%, p=0.001) and deep layers (+100%, p=0.017) of
      the PCC in the schizophrenia group. No difference was observed for [(3)H]AF-DX
      384 binding between the schizophrenia and control groups. The authors found a
      significant inverse correlation between [(3)H]pirenzepine binding in the deep
      cortical layers and [(3)H]muscimol binding in the superficial layers (rho=-0.732,
      p=0.003). In addition, negative correlations were also found between age and
      [(3)H]pirenzepine binding in both superficial and deep cortical layers (rho=
      0.669 p=0.049 and rho=-0.778, p=0.014), and between age of schizophrenia onset
      and [(3)H]AF-DX 384 binding (rho=-0.798, p=0.018). These results for the first
      time demonstrated the status of M1/M4, M2/M4 and GABA(A) receptors in the PCC in
      schizophrenia. Whilst the exact mechanism causing these alterations is not yet
      known, a possible increased acetylcholine and down regulated GABA stimulation in
      the PCC of schizophrenia is suggested.

PMID- 16901599
TI  - Vernier threshold and the parallel visual pathways in bipolar disorder: a follow
      up study.
AB  - Magnocellular (M) and parvocellular (P) visual pathways participate in the
      processing of low contrast and colors of objects, respectively. The aim of this
      study was to investigate M and P pathway functions in bipolar disorder during a
      depressive episode and after the amelioration of symptoms. Participants (17
      patients with type I bipolar disorder and 20 matched healthy controls) received
      two vernier tasks. During the M pathway test, stimuli were dots with low
      luminance-contrast (5%), whereas during the P pathway test, isoluminant blue dots
      were presented against a yellow background. Participants were asked to detect the
      direction of the horizontal displacement of the dots (left or right). The
      assessment was performed during a depressive state and during a clinically
      improved state after 2 months. During the depressive state, the patients showed
      significantly impaired M and P pathway functions, whereas during the clinically
      improved state, their performance was better and was statistically
      indistinguishable from that of the controls. In conclusion, M and P pathways are
      impaired in depressed bipolar patients. This deficit is ameliorated along with
      clinical improvement. Further studies are necessary to separately assess cortical
      and precortical stages of information-processing, and to exclude the possibility
      of general motivational and attentional impairments.

PMID- 16901600
TI  - Psychological traits and platelet monoamine oxidase activity in eating disorder
      patients: their relationship and stability.
AB  - Self-reported behavior and attitudes towards eating [Eating Disorder Inventory-2;
      Garner DM (1991). Eating Disorder Inventory-2: Professional Manual. Odessa, Fl.:
      Psychological Assessment Resources; Estonian version Podar I, Hannus A, Allik J
      (1999). Personality and Affectivity Characteristics Associated With Eating
      Disorders: a Comparison of Eating Disordered, Weight-Preoccupied, and Normal
      Samples. J Pers Assess; 73(1), 133-147] and the activity of platelet monoamine
      oxidase (MAO) was studied in 11 patients with anorexia nervosa (AN), 43 patients
      with bulimia nervosa (BN) and a healthy control group (n=138). Nineteen patients
      filled in the EDI-2 questionnaire and donated blood samples three times with
      three month intervals in order to determine platelet MAO activity. Eating
      disordered (ED) patients scored higher on all EDI-2 subscales and had lower MAO
      activity compared to the control group. They also scored higher than the control
      group on the Neuroticism domain but lower on the Extraversion, Openness, and
      Conscientiousness domains of the NEO-PI-R questionnaire. The average stability of
      MAO on different occasions (r=.56) was slightly smaller than the stability of the
      EDI-2 scores (r=.70). The lack of correlations between personality dispositions
      and MAO activity indicates that they have independent influence on eating
      disorders. A possible relationship between neurochemical mechanisms and
      psychological symptoms of eating disordered behavior is discussed.

PMID- 16901601
TI  - Genotoxicity testing of a Salacia oblonga extract.
AB  - Salacia oblonga has been used for thousands of years in Ayurvedic medicine for
      the oral treatment of diabetes. The root extract has been shown to inhibit the
      activity of intestinal alpha-glucosidases, therefore S. oblonga holds potential
      as a natural method to mitigate the blood glucose response for people with
      diabetes. As part of a safety evaluation of novel ingredients for use in blood
      glucose control, the potential genotoxicity of a S. oblonga root extract (SOE)
      was evaluated using the standard battery of tests (reverse mutation assay;
      chromosomal aberrations assay; mouse micronucleus assay) recommended by US Food
      and Drug Administration (FDA) for food ingredients. SOE was determined not to be
      genotoxic under the conditions of the reverse mutation assay and mouse
      micronucleus assay, and weakly positive for the chromosomal aberrations assay. A
      reproducible, although weak, positive chromosomal aberrations response in human
      lymphocytes is of concern and further toxicity research is recommended. Use of
      SOE is presently expected to be safe, as anticipated intake is small compared to
      the doses administered in the genotoxicity assays and may, after further toxicity
      research, may prove be a useful ingredient in foodstuffs.

PMID- 16901602
TI  - Preliminary study of Ochratoxin A in human plasma in agricultural zones of Chile
      and its relation to food consumption.
AB  - Ochratoxin A (OTA) is a mycotoxin produced by different species of Aspergillus
      and Penicillium fungi. The presence of OTA in human blood has been reported in
      many studies, especially in Europe, however none have been done in South America.
      In this study, 88 blood samples from healthy donors from two different Chilean
      agricultural zones were analyzed. In parallel with sample collection, the donors
      filled a questionnaire regarding food intake during the last three months. The
      blood samples were collected in Colbun in March and July of 2004 and in San
      Vicente de Tagua--Tagua in October of 2004. The extraction procedure was done in
      the solid phase with a Sep-Pak RP-18 cartridge and a final purification with
      immunoaffinity Ochraprep columns. The presence of OTA was confirmed by the
      formation of Ochratoxin A methyl ester. Fifty four percent of the samples
      collected in Colbun and 91% of samples from San Vicente de Tagua - Tagua were
      positive to OTA at ranges of 0.07-2.75 ppb and 0.22-2.12 ppb, respectively. The
      OTA levels in serum did not show a good correlation with normal dietary
      consumption.

PMID- 16901603
TI  - Total arsenic, inorganic arsenic, lead and cadmium contents in edible seaweed
      sold in Spain.
AB  - Total arsenic, inorganic arsenic, lead and cadmium contents were determined in
      112 samples of seaweed preparations sold in Spain (seaweed packed in plastic or
      cardboard box, seaweed in the form of tablets and concentrates, foods containing
      seaweed, and canned seaweed). The concentration ranges found, expressed in mg/kg,
      dry weight, were: total As (0.031-149), inorganic As (<0.014-117), Pb (<0.050
      12.1) and Cd (<0.003-3.55). For all the contaminants there were failures to
      comply with legislated values. In particular, all the samples of Hizikia
      fusiforme exceeded the inorganic As limit established in some countries, and a
      considerable number of species exceeded the Cd limit set by international
      regulations. With respect to food safety, consumption of 3 g/day of the samples
      analysed could represent up to 15% of the respective Tolerable Daily Intakes
      (TDI) established by the WHO. The situation is especially alarming for intake of
      inorganic As from H. fusiforme, which can be three times the TDI established.

PMID- 16901604
TI  - Prior administration of a low dose of thioacetamide protects type 1 diabetic rats
      from subsequent administration of lethal dose of thioacetamide.
AB  - Previously, we reported that an ordinarily non-lethal dose of thioacetamide (TA,
      300 mg/kg) causes 90% mortality in type 1 diabetic rats due to inhibited liver
      tissue repair, whereas 30 mg TA/kg allows 100% survival due to stimulated
      although delayed tissue repair. Objective of this investigation was to test
      whether prior administration of a low dose of TA (30 mg/kg) would lead to
      sustainable stimulation of liver tissue repair in type 1 diabetic rats sufficient
      to protect from a subsequently administered lethal dose of TA. Therefore, in the
      present study, the hypothesis that preplacement of tissue repair by a low dose of
      TA (30 mg TA/kg, ip) can reverse the hepatotoxicant sensitivity (autoprotection)
      in type 1 diabetic rats was tested. Preliminary studies revealed that a single
      intraperitoneal (ip) administration of TA causes 90% mortality in diabetic rats
      with as low as 75 mg/kg. To establish an autoprotection model in diabetic
      condition, diabetic rats were treated with 30 mg TA/kg (priming dose).
      Administration of priming dose stimulated tissue repair that peaked at 72h, at
      which time these rats were treated with a single ip dose of 75 mg TA/kg. Our
      results show that tissue repair stimulated by the priming dose enabled diabetic
      rats to overexpress, calpastatin, endogenous inhibitor of calpain, to inhibit
      calpain-mediated progression of liver injury induced by the subsequent
      administration of lethal dose, resulting in 100% survival. Further investigation
      revealed that protection observed in these rats is not due to decreased
      bioactivation. These studies underscore the importance of stimulation of tissue
      repair in the final outcome of liver injury (survival/death) after hepatotoxicant
      challenge. Furthermore, these results also suggest that it is possible to
      stimulate tissue repair in diabetics to overcome the enhanced sensitivity of
      hepatotoxicants.

PMID- 16901606
TI  - Caries detection and diagnosis: novel technologies.
AB  - Recent years have seen an increase in research activity surrounding diagnostic
      methods, particularly in the assessment of early caries lesions. The drive for
      this has come from two disparate directions. The first is from the dentifrice
      industry who are keen to develop techniques that would permit caries clinical
      trials (CCTs) to be reduced in duration and subject numbers to permit the
      investigation of novel new anti-caries actives. The second is from clinicians
      who, armed with the therapies to remineralise early lesions are now seeking
      methods to reliably detect such demineralised areas and implement true
      preventative dentistry. This review examines novel technologies and the research
      supporting their use. Techniques based on visual, optical, radiographic and some
      emerging technologies are discussed. Each have their benefits although systems
      based on the auto-fluorescence (such as QLF) of teeth and electrical resistance
      (such as ECM) seem to offer the most hope for achieving reliable, accurate
      detection of the earliest stages of enamel demineralisation.

PMID- 16901605
TI  - Bifunctional modulating effects of an indigo dimer (bisindigotin) to CYP1A1
      induction in H4IIE cells.
AB  - In this study, we measured and characterized the bifunctional effects of a newly
      identified natural compound-bisindigotin (SLY-1), isolated from leaf extracts of
      Isatis indigotica, to CYP1A1/EROD activities in H4IIE cells. The compound, SLY-1
      (1muM) elicited a transitory and significant induction of CYP1A1 RNA/protein
      levels and EROD activities in the cells. Maximum levels of CYP1A1 expression and
      EROD induction were attained at 8 and 12h of post-treatment, respectively.
      Thereafter the induction decreased significantly. Similar profile of CYP1A2 and
      CYP1B1 mRNA induction was observed. In contrast TCDD elicited CYP1A1/EROD
      induction was persistent. The transitory effect by SLY-1 is most likely due to
      the clearance of SLY-1 by cellular metabolism. Taken together the observation
      indicated that SLY-1 is an Ah receptor agonist for CYP1A1/CYP1A2/CYP1B1/EROD
      induction. Interestingly in the TCDD/SLY-1 cotreatment study, although
      synergistic effects on CYP1A1 expression and EROD induction were observed at 4
      8h, significant inhibitory effects to TCDD induced CYP1A1 protein and EROD
      activity were detected at 12-24h of post-treatment. Because there was no
      significant reduction of CYP1A1, CYP1A2 or CYP1B1 transcript levels between TCDD-
      and TCDD/SLY-1 treated cells, the data pointed to the translational and/or post
      translational inhibitory effect. The cellular signal transduction system may be
      modulated following exposure to SLY-1. To investigate the possible mechanisms
      involved, various specific kinase inhibitors or activators (chelerythrin,
      PD98059, U0126, ZM336372, SB202190, PKA inhibitor PKI (6-22) amide, and dbcAMP)
      were used for the assessment. Chelerythrine, PD98059 or dbcAMP treatment in TCDD
      induced cells showed significant inhibitory effects on CYP1A1 mRNA/protein
      expressions and EROD activities. U0126 had no observable EROD inhibitory effect.
      ZM336372 or SB202190 showed inhibition only at EROD activities. The results
      indicated that the SLY-1 inhibitory effect was possibly not mediated by the
      cAMP/PKA, PKC or MEK pathways. Nevertheless our results indicate that SLY-1 is
      not only an inducer of the CYP1A1 system, but also a potent inhibitor of CYP1A1
      enzyme.

PMID- 16901607
TI  - Hypomagnesaemia causing QT interval prolongation and torsade de pointes in an
      alcoholic patient.

PMID- 16901608
TI  - A new tracheal tube and methods to facilitate ventilation and placement in
      emergency airway management.
AB  - The "jet endotracheal tube" (JET) has been designed to facilitate emergency
      intubation in apnoeic or paralyzed patients with a difficult airway. We
      investigated the efficiency of jet ventilation to maintain adequate oxygenation
      and ventilation using the initially designed JET, either with its distal tip
      positioned above vocal cord and pointed directly at or 45 degrees to the right of
      the vocal cord opening midline in 10 adult paralyzed pigs. The effectiveness of
      using end tidal carbon dioxide pressure (PetCO(2)), chest rise and breath sounds
      to facilitate tracheal placement of the JET blindly in a simulated difficult
      airway was studied. All complications of using the JET were noted. Jet
      ventilation with the distal tip of the JET pointed directly at, not 45 degrees to
      the right of vocal cord opening midline, provides adequate oxygenation and
      ventilation during intubation. In a simulated difficult airway, PetCO(2), chest
      rise and breath sounds were all effective methods to assist placement of the JET
      blindly, and the combination of all three methods works the best. No serious
      complications were detected with the use of the JET. Our results suggest that a
      correctly positioned JET guided by monitoring PetCO(2), chest rise and breath
      sound provides adequate oxygenation and ventilation during intubation in apnoeic
      pigs, and facilitates the intubation blindly in a simulated difficult airway. No
      serious complications were observed using the JET in this study. In patients
      requiring emergency intubation, a JET with PetCO(2) monitoring catheter and the
      instructions for use may be a useful addition to the airway management devices.

PMID- 16901609
TI  - Anaphylaxis to intrathecal diamorphine.
AB  - A 42-year-old male underwent a total hip arthroplasty under subarachnoid
      anaesthesia with intrathecal bupivacaine and diamorphine. Shortly after the start
      of surgery, he suffered an allergic reaction that, at first, was difficult to
      distinguish from the recognised side-effects of intrathecal diamorphine. Once the
      diagnosis was made, he was treated with adrenaline and made a full recovery. The
      serum concentration of mast cell tryptase approximately 1.5h after the onset of
      the adverse incident confirmed an anaphylactic reaction. Skin prick testing
      several weeks later identified diamorphine as the likely causative agent, a drug
      overlooked initially as a potential cause. We believe this is the first report of
      intrathecal diamorphine causing anaphylaxis.

PMID- 16901610
TI  - One-handed versus two-handed chest compressions in paediatric cardio-pulmonary
      resuscitation.
AB  - OBJECTIVES: To determine emergency department (ED) staff preference for one- or
      two-handed paediatric chest compressions and to determine if there was a
      difference in compression rates delivered and fatigability between the
      techniques. METHODS: This was a randomised, cross-over observational study of
      paediatric CPR performed on a standard paediatric manikin by ED staff.
      Consenting, eligible staff [ED doctors and nurses] performed CPR in pairs with
      chest compressions delivered using a one- and two-handed technique. The outcomes
      of interest were compression rates for one- and two-handed CPR, decrease in
      compression rate over time for each technique and staff preference for technique.
      Data was analysed using descriptive statistics, Chi Square test and Mann-Whitney
      U-test as appropriate. RESULTS: Sixty-two ED staff participated in the study.
      Compression rates with both techniques were similar and higher than guidelines
      recommend (133.6 min(-1) for one-handed and 135.7 min(-1) for two-handed
      respectively). The compression rate slowed by 6.9 compressions/min over 1 min in
      one-handed compressions compared with 2.6 compressions/min in two-handed
      compressions (p = 0.0264). 65.6% of participants reported that they preferred the
      two-handed compression technique. CONCLUSION: This study showed that CPR
      compression rate is similar with one- and two-handed compression techniques, but
      compression rate decreased more quickly with the one-handed technique. The
      majority of staff preferred the two-handed compression technique for reasons of
      ease, control and uniformity with other CPR techniques.

PMID- 16901611
TI  - Intrathoracic pressure regulation improves vital organ perfusion pressures in
      normovolemic and hypovolemic pigs.
AB  - BACKGROUND: The intrathoracic pressure regulator (ITPR) was created to improve
      hemodynamics by generating continuous negative airway pressure between positive
      pressure ventilations to enhance cardiac preload in apnoeic animals. In
      normovolemic and hypovolemic pigs, we tested the hypothesis that continuous
      negative intrathoracic pressure set at -5 or -10mmHg, interrupted only for
      intermittent positive pressure ventilations, would decrease intracranial (ICP)
      and right atrial (RAP) pressure, and increase mean arterial pressure (MAP).
      METHODS: Twelve pigs were anesthetized with propofol and ventilated with a bag.
      The ITPR was used to vary baseline endotracheal pressures (ETPs) for 5min periods
      in the following sequence: 0, -5, 0, -10, 0mmHg under normovolemic conditions.
      Six pigs were bled 50% (32.5+/-mL/kg) of their estimated blood volume and the
      airway pressure sequence was repeated. Six other pigs were bled 35% (22.75+/
      mL/kg) of their estimated blood volume and the same airway pressure sequence was
      repeated. Intracranial, aortic, right atrial pressures, arterial blood gases, end
      tidal CO(2) (ETCO(2)), were measured. ANOVA was used for statistical analysis.
      Linear regression analysis was performed for ETP and ICP. RESULTS: Mean arterial
      and vital organ perfusion pressures were significantly improved and RA pressure
      significantly decreased with the use of the ITPR; the effect was greater with the
      more negative ETPs and lower circulating blood volume. The change of ICP was
      linearly related to the ETP and blood loss: DeltaICP=[1.22-0.84(1-%blood
      loss/100)]xETP, r(2)=0.88 (in mmHg), p<0.001. There were no adverse device
      effects and there was a significant increase of ETCO(2) with the use of ITPR.
      CONCLUSION: The ITPR decreased RAP and ICP significantly and improved mean
      arterial and cerebral and coronary perfusion pressures without affecting acid
      base balance severely. The decrease in ICP was directly proportional to the
      reduction in intrathoracic pressure. The effects were more pronounced in severe
      hypovolemic and hypotensive states with more negative ETP pressure.

PMID- 16901612
TI  - Emergency medical services: Brazil.
AB  - Emergency medical services in Brazil have been created to offer first aid,
      primary medical treatment, basic life support, stabilization and rapid transfer
      to the closest appropriate hospital and advanced life support. Pre-hospital
      emergency care in Brazil is divided into permanent and mobile services. Permanent
      care is provided by the pre-hospital network (basic health units, family health
      program, specialized clinics, diagnosis and therapy services, non-hospital
      emergency care units). The mobile medical services include: mobile emergency care
      service, fire department and private services. Emergency hospital care units
      (emergency departments) are classified into general and reference units. Details
      of these services are described.

PMID- 16901613
TI  - Resuscitation great. Leon Chameides: a gentle giant and the father of pediatric
      resuscitation.

PMID- 16901614
TI  - Serum cardiac markers response to biphasic and monophasic electrical
      cardioversion for supraventricular tachyarrhythmia--a randomised study.
AB  - BACKGROUND: Electrical cardioversion in patients with various types of
      supraventricular tachyarrhythmia (SVT) may induce serum cardiac markers
      elevation. Only a few studies have evaluated the impact of the type of shock
      waveform on electrical myocardial injury. The aim of our study was to compare the
      response of serum cardiac markers to biphasic and monophasic cardioversion for
      SVT. METHODS: One hundred and forty one patients with various SVTs referred for
      electrical cardioversion were randomised to monophasic (MP) or biphasic (BP)
      cardioversion. Serum levels of creatine kinase (CK), MB fraction of CK (CK-MB),
      myoglobin and troponin I were analysed before cardioversion and 254+/-58 min
      after the procedure. RESULTS: Average age of the patients was 67.9+/-11.3 years,
      71 underwent BP and 70 MP cardioversion. In MP group, cumulative energy (CE)>150J
      was associated with significant elevation of CK and myoglobin levels after
      cardioversion (1.52+/-3.81 microkat/l and 187+/-433 microg/l), while CE<150J was
      not (-0.04+/-0.34 and 4+/-11, p<0.05). In BP group, CE>150J was associated with
      significant but smaller CK elevation (0.27+/-1.09 microkat/l, p<0.05) and
      comparable myoglobin elevation (80.7+/-21.4 microg/l, p<0.05). CE>150J was the
      only independent positive predictor for CK and myoglobin elevation in both
      groups. No significant changes in CK-MB and Troponin I levels after cardioversion
      were identified. CONCLUSIONS: According to our study, electrical cardioversion
      for SVTs is not associated with biochemical signs of myocardial injury.
      Application of CE>150J can be followed by CK and myoglobin elevation most likely
      due to skeletal muscle damage. This reaction is more pronounced in MP than in BP
      cardioversion.

PMID- 16901615
TI  - Cardiac arrest in public locations--an independent predictor for better outcome?
AB  - OBJECTIVE: Outcome after cardiac arrest is known to be influenced by immediate
      access to resuscitation. We aimed to analyse the location of arrest in relation
      to the prognostic value for outcome. DESIGN: Retrospective review from
      prospective databases (ambulance routine documentation database and emergency
      department database on patients treated for cardiac arrest). SETTING: Vienna (1.7
      million inhabitants) ambulance service and tertiary care facility (university
      clinics). PATIENTS: Two independent cohorts: (1) a population-based cohort of
      patients who were treated for cardiac arrest by the municipal ambulance service
      outside the hospital. The endpoint in this group was survival to hospital
      admission with spontaneous circulation. (2) A cohort of patients who were
      admitted to the emergency department after successful out of hospital
      resuscitation. The endpoint in this group was survival to 6 months with good
      neurological status (best Cerebral Performance Category 1 or 2 within 6 months).
      MEASUREMENTS: We analysed whether the location of non-traumatic adult out-of
      hospital cardiac arrest (public versus private place) was a predictor for good
      outcome. RESULTS: PATIENTS who had cardiac arrest in a public location were more
      likely to arrive in hospital alive (39% versus 31%, crude OR 1.4, 95% CI 1.001
      1.975, p=0.049) and were more likely to have a good neurological outcome after 6
      months (35% versus 25%, crude OR 1.65, adjusted OR 1.59, 95% CI 1.07-2.36,
      p=0.023), compared to patients who had cardiac arrest in a non-public location.
      CONCLUSION: Cardiac arrest in a public location is independently associated with
      a better outcome.

PMID- 16901616
TI  - Roles of periventricular neurons in retinotectal transmission in the optic
      tectum.
AB  - The midbrain roof is a retinorecipient region referred to as the optic tectum in
      lower vertebrates, and the superior colliculus in mammals. The retinal fibers
      projecting to the tectum transmit visual information to tectal retinorecipient
      neurons. Periventricular neurons are a subtype of these neurons that have their
      somata in the deepest layer of the teleostean tectum and apical dendrites
      ramifying at more superficial layers consisting of retinal fibers. The
      retinotectal synapses between the retinal fibers and periventricular neurons are
      glutamatergic, and ionotropic glutamate receptors mediate the transmission in
      these synapses. This transmission involves long-term potentiation, and is
      modulated by hormone action. Visual information processed in the periventricular
      neurons is transmitted to adjacent tectal cells and target nuclei of
      periventricular neuron axonal branches, some of which relay the visual
      information to other brain areas controlling behavior. We demonstrated that
      periventricular neurons play a principal role in visual information processing in
      the teleostean optic tectum; the effects of tectal output on behavior is
      discussed also in the present review.

PMID- 16901617
TI  - Predicting streamflow response to fire-induced landcover change: implications of
      parameter uncertainty in the MIKE SHE model.
AB  - Fire is a primary agent of landcover transformation in California semi-arid
      shrubland watersheds, however few studies have examined the impacts of fire and
      post-fire succession on streamflow dynamics in these basins. While it may seem
      intuitive that larger fires will have a greater impact on streamflow response
      than smaller fires in these watersheds, the nature of these relationships has not
      been determined. The effects of fire size on seasonal and annual streamflow
      responses were investigated for a medium-sized basin in central California using
      a modified version of the MIKE SHE model which had been previously calibrated and
      tested for this watershed using the Generalized Likelihood Uncertainty Estimation
      methodology. Model simulations were made for two contrasting periods, wet and
      dry, in order to assess whether fire size effects varied with weather regime.
      Results indicated that seasonal and annual streamflow response increased nearly
      linearly with fire size in a given year under both regimes. Annual flow response
      was generally higher in wetter years for both weather regimes, however a clear
      trend was confounded by the effect of stand age. These results expand our
      understanding of the effects of fire size on hydrologic response in chaparral
      watersheds, but it is important to note that the majority of model predictions
      were largely indistinguishable from the predictive uncertainty associated with
      the calibrated model - a key finding that highlights the importance of analyzing
      hydrologic predictions for altered landcover conditions in the context of model
      uncertainty. Future work is needed to examine how alternative decisions (e.g.,
      different likelihood measures) may influence GLUE-based MIKE SHE streamflow
      predictions following different size fires, and how the effect of fire size on
      streamflow varies with other factors such as fire location.

PMID- 16901618
TI  - A GIS-based approach for the screening assessment of noise and vibration impacts
      from transit projects.
AB  - Urban transportation projects are essential in increasing the efficiency of
      moving people and goods within a city, and between cities. Environmental impacts
      from such projects must be evaluated and mitigated, as applicable. Spatial
      modeling is a valuable tool for quantifying the potential level of environmental
      consequences within the context of an environmental impact assessment (EIA)
      study. This paper presents a GIS-based tool for the assessment of airborne-noise
      and ground-borne vibration from public transit systems, and its application to an
      actual project. The tool is based on the US Federal Transit Administration's
      (FTA) approach, and incorporates spatial information, satellite imaging,
      geostatistical modeling, and software programming. The tool is applied on a case
      study of initial environmental evaluation of a light rail transit project in an
      urban city in the Middle East, to evaluate alternative layouts. The tool readily
      allowed the alternative evaluation and the results were used as input to a multi
      criteria analytic framework.

PMID- 16901619
TI  - Impacts of a participatory approach to developing national level sustainable
      development indicators in Finland.
AB  - The paper explores the role of a participatory approach in the outcome of the
      Finnish sustainable development indicator (SDI) exercise in 1998-2002. The
      process is analysed through three main objectives: to achieve stronger democracy,
      better quality of the end product and a more effective process. The analysis is
      further structured by a set of criteria needed for successful participation and
      differentiation of types of participants. The criteria comprise three main
      aspects: fairness, competence and social learning. In addition to the normally
      mentioned stakeholders (e.g. citizens and interest groups) participants also
      include experts and civil servants. Using the set of criteria above the
      participatory approach of the Finnish SDI process is then evaluated, and in the
      light of this evaluation the paper also discusses the specifications needed as
      evaluation criteria for national level policy programme processes like developing
      the SDIs. The results are based on documentation of the indicator task force
      meetings, written comments and a study of the putative end-users conducted after
      the publication of the indicators. The results show that the intense and broad
      participation of experts and civil servants increased the competence of the
      outcome and led to greater efficiency in working methods. However, this led to
      technocratic participation, absence of democratic participation and absence of
      social learning. Thus the ultimate goal of SDIs to contribute to achieving
      sustainability was not reached.

PMID- 16901620
TI  - Design principles and common pool resource management: an institutional approach
      to evaluating community management in semi-arid Tanzania.
AB  - This paper analyses the role of institutions in the management of common pool
      resources (CPRs) in semi-arid Tanzania. Common property regimes have often been
      considered inadequate for the management of CPRs because of the problems of
      excludability, but they are becoming more widely supported as the way forward to
      overcome the problems of resource use and degradation in developing countries. A
      series of design principles for long enduring common property institutions have
      been proposed by Ostrom, but there is concern that they are not applicable to a
      wide range of real life situations or that they may be specific to certain types
      of CPR. Here, we compare these principles to the situation prevailing in 12
      villages in six districts in semi-arid Tanzania. Data on management institutions
      were collected through semi-structured interviews and meetings at district and
      village level. The combined information was used to make a qualitative assessment
      of the strength with which each design principle appeared to operate in the
      management of forest, pasture and water resources. Boundaries, conflict and
      negotiation in CPR management are of key importance in semi-arid regions.
      However, the need for flexibility in order to deal with ecological uncertainty
      means that many management institutions would be considered weak or absent
      according to the design principle approach. This supports the view that the
      design principles should not be used as a 'blueprint to be imposed on resource
      management regimes' rather that they provide a framework for investigating common
      property regimes with the proviso that, certainly for semi-arid regions, they may
      highlight where management cannot be explained by institutional theory alone.

PMID- 16901621
TI  - A pilot-plant study for destruction of PCBs in contaminated soils using fluidized
      bed combustion technology.
AB  - Destruction of polychlorinated biphenyls (PCBs) in contaminated soils and wastes
      using circulating fluidized bed combustion (CFBC) technology was studied using a
      pilot plant and simulated waste material. The results show that the technology is
      effective and particularly promising for treatment of PCB-containing materials
      like the toxic sludge from a large contaminated site. Destruction of the toxics
      in the gas phase appears to be very fast, and over 99.9999% destruction and
      removal efficiency can be achieved in the temperature range 875-880 degrees C.
      Heat transfer in the fluidized bed also appears adequate. Toxic residues in
      treated soil can be reduced to very low levels. Rate-controlling factors of the
      decontamination process are analyzed, and key issues for determination of the
      process conditions are discussed.

PMID- 16901622
TI  - A pretreatment table for the prediction of final histopathology after radical
      prostatectomy in clinical unilateral T3a prostate cancer.
AB  - OBJECTIVES: Partin tables are the most widely used tool to predict
      histopathologic stage after radical prostatectomy (RP) in organ-confined tumors.
      Such a predictive table in clinical T3 disease is still lacking. Our objective
      was to create a reference table for clinical unilateral T3a prostate cancer.
      PATIENTS AND METHODS: Between 1987 and 2004, 200 patients with clinical
      unilateral T3a disease underwent a RP and bilateral pelvic lymphadenectomy at our
      institution. No patient had received neoadjuvant treatment. Patients were divided
      into three prostate-specific antigen (PSA) subgroups (<or=10 ng/ml, >10-20 ng/ml,
      and >20 ng/ml) and two biopsy Gleason sum (GS) subgroups (<or=7 [3+4] and >or=7
      [4+3]). These parameters were used in the table as predictors for final
      histopathology. Margin and nodal status were also recorded. The multinomial log
      linear regression analysis was used to construct the table. RESULTS: The table
      stratifies patients into six demarcated risk groups. In the first group,
      consisting of patients with PSA <or=10 and GS <or=7 (3+4), understaging was only
      6% (5% pT3b and 1% pT4). The risk for understaging cT3a prostate cancer increases
      further with increasing PSA and GS. In the sixth group, consisting of patients
      with PSA >20 and GS >or=7 (4+3), understaging was as high as 68% (44% pT3b and
      22% pT4). Receiver operating characteristic analyses showed good accurate
      predictive ability of the table for seminal vesicle involvement and adjacent
      structure involvement, with moderate predictive ability for extraprostatic
      extension only. CONCLUSIONS: We present a table combining preoperative serum PSA
      and biopsy GS to predict histopathologic results in clinical unilateral T3a
      prostate cancer. The table may provide a basis for decision-making and patient
      counseling before treating this cancer.

PMID- 16901623
TI  - Association between erectile dysfunction and coronary artery disease: Matching
      the right target with the right test in the right patient.
AB  - INTRODUCTION: Evidence is accumulating in favour of a link between erectile
      dysfunction (ED) and coronary artery disease (CAD). This review attempts to
      identify which patients, among those with ED and no cardiovascular (CV) disease,
      should be screened for early, subclinical CAD, which coronary targets should be
      investigated, and which tests should be used. MATERIALS AND METHODS: A
      comprehensive evaluation of available published data included analysis of
      published full-length papers that were identified with Medline and Cancerlit from
      January 1988 to January 2006. RESULTS: Initial screening of patients with ED may
      adopt risk assessment office-based approaches to score patients into low,
      intermediate, or high risk of future cardiovascular events. Attention should be
      drawn to patients at intermediate risk. Targets for the assessment of subclinical
      CAD in this subset of patients should include both obstructive (flow-limiting)
      and nonobstructive (non-flow-limiting) CAD. Some tests address obstructive
      atherosclerosis by directly assessing coronary flow reserve (i.e., standard
      exercise stress test, rest/stress myocardial scintigraphy or echocardiography).
      Other tests are general measures of atherosclerosis burden (not necessarily
      obstructive) either in the coronary circulation (i.e., coronary calcium score by
      electron-beam computed tomography), or in extracoronary vessels (i.e., ankle
      brachial index, carotid intima-media thickness by B-mode ultrasound) as surrogate
      markers of CAD. Although a systematic use of these measures of nonobstructive
      atherosclerosis burden has not yet been recommended in the guidelines for
      coronary risk assessment, their use is progressively being extended from the
      research area to clinical practice. CONCLUSIONS: ED is definitely a vascular
      disorder and all men with ED should be considered at risk of CV disease until
      proven otherwise. Available risk assessment charts should be used to stratify
      (low, intermediate, and high) the coronary risk score in each patient with ED.

PMID- 16901624
TI  - Prevention and management of complications in urological laparoscopic port site
      placement.
AB  - OBJECTIVES: To review complications associated with urological laparoscopic port
      site placement and outline techniques for their prevention and management.
      METHODS: Review of the literature using Medline. RESULTS: Laparoscopy now plays a
      key role in urological surgery. Its applications are expanding with experience
      and evolving data confirming equivalent long-term outcome. Although significant
      port-site complications are uncommon, their occurrence impacts significantly on
      perioperative morbidity and rate of recovery. The incidence of such complications
      is inversely related to surgeon experience. Ports now utilise bladeless tips to
      reduce the incidence of vascular and visceral injuries, and subsequently port
      site herniation. Metastases occurring at the port site are preventable by
      adhering to certain measures. CONCLUSIONS: Whether performing standard or robot
      assisted laparoscopy, port-site creation and maintenance is critical in ensuring
      minimal invasiveness in laparoscopic urological surgery. Although patient factors
      can be optimised perioperatively and port design continues to improve, it is
      clear that adequate training is central in the prevention, early recognition, and
      treatment of complications related to laparoscopic access.

PMID- 16901626
TI  - Thermal treatment of toxic metals of industrial hazardous wastes with fly ash and
      clay.
AB  - Waste generated from galvanizing and metal finishing processes is considered to
      be a hazardous due to the presence of toxic metals like Pb, Cu, Cr, Zn, etc.
      Thermal treatment of such types of wastes in the presence of clay and fly ash can
      immobilizes their toxic metals to a maximum level. After treatment solidified
      mass can be utilized in construction or disposed off through land fillings
      without susceptibility of re-mobilization of toxic metals. In the present
      investigation locally available clay and fly ash of particular thermal power
      plant were used as additives for thermal treatment of both of the wastes in their
      different proportions at 850, 900 and 950 degrees C. Observed results indicated
      that heating temperature to be a key factor in the immobilization of toxic metals
      of the waste. It was noticed that the leachability of metals of the waste reduces
      to a negligible level after heating at 950 degrees C. Thermally treated
      solidified specimen of 10% waste and remaining clay have shown comparatively a
      higher compressive strength than clay fired bricks used in building construction.
      Though, thermally heated specimens made of galvanizing waste have shown much
      better strength than specimen made of metal finishing waste. The lechability of
      toxic metals like Cr, Cu, Pb and Zn became far below from their regulatory
      threshold after heating at 950 degrees C. Addition of fly ash did not show any
      improvement either in engineering property or in leachability of metals from the
      solidified mass. X-ray diffraction (XRD) analysis of the solidified product
      confirmed the presence of mixed phases of oxides of metals.

PMID- 16901627
TI  - Characterization and distribution of polycyclic aromatic hydrocarbon in surface
      water and sediment from Qiantang River, China.
AB  - The spatial and temporal distribution of polycyclic aromatic hydrocarbons (PAHs)
      has been investigated in Qiantang River, an important drinking water resource in
      Yangzi River Delta, China. A total of 218 samples, including 180 water and 38
      sediment samples were collected in January, April, July and October, 2005. The
      concentrations of total PAHs in water ranged from 70.3 to 1844.4ng/L with the
      mean value of 283.3ng/L, which were predominated by two- and three-ring PAHs. The
      concentration of total 15 PAHs in sediment ranges from 91.3 to 614.4ng/g dry
      weight with the mean value of 313.1ng/g dry weight, and three- and four-ring PAHs
      were dominant species. The ratios of AN/(AN+Phen) and Flur/(Flur+Pye) were
      calculated to evaluate the possible sources of PAHs. These ratios reflected a
      pattern of petrogenic input of PAHs in Qiantang River. The contents of PAHs in
      city zones were much higher than those in rural areas. It may be concluded that
      the urbanization and industrialization are causing some negative effect on the
      drinking water resource. As a drinking water resource, there existed certain
      potential health risks to drinking water consumers and organism in Qiantang River
      Basin.

PMID- 16901628
TI  - Equilibrium, kinetic and thermodynamic studies of adsorption of fluoride onto
      plaster of Paris.
AB  - Batch sorption system using plaster of Paris as an adsorbent was investigated to
      remove fluoride ions from aqueous solutions. The system variables studied include
      initial concentration of the sorbate, agitation time, adsorbent dose, pH, co-ions
      and temperature. The experimental data fitted well to the Freundlich and Langmuir
      isotherms. Thermodynamic parameters such as DeltaH degrees , DeltaS degrees and
      DeltaG degrees were calculated indicating that the adsorption was a spontaneous
      and exothermic. Kinetic studies reveal that the adsorption is first order. A
      mechanism involving three stages (external surface adsorption, intraparticle
      diffusion and final equilibrium) has been proposed for the adsorption of F(-)
      onto plaster of Paris. XRD patterns of the adsorbent were recorded to get a
      better in sight into the mechanism of adsorption process.

PMID- 16901629
TI  - Biosorption of methylene blue from aqueous solution by fallen phoenix tree's
      leaves.
AB  - A new adsorbent, the fallen phoenix tree's leaf, has been investigated in order
      to remove methylene blue (MB) from aqueous solutions. Variables of the system,
      including contact time, leaf dose, solution pH, salt concentration and initial MB
      concentration, were adopted to study their effects on MB biosorption. The results
      showed that as the dose of leaf increased, the percentage of MB sorption
      increased accordingly. There was no significant difference about the quantity of
      MB adsorbed onto leaf as the pH was within the range 4.5-10.0. The salt
      concentration has negative effect on MB removal. The equilibrium data were
      analyzed using the Langmuir and the Freundlich isotherms. The results of non
      linear regressive analysis are that the Langmuir isotherm is better fit than the
      Freundlich isotherm at different temperature according to the values of
      determined coefficients (R(2)) and chi(2)-statistic (SS). The Langmuir monolayer
      saturation capacities of MB adsorbed onto leaf are 80.9, 83.8, 89.7mgg(-1) at
      295, 309 and 323K, respectively. Using the equilibrium concentration contents
      obtained at different temperatures, various thermodynamic parameters, such as
      DeltaG degrees , DeltaH degrees and DeltaS degrees , have been calculated. The
      thermodynamics parameters of MB/leaf system indicate spontaneous and endothermic
      process. It was concluded that an increase in temperature be advantage to adsorb
      MB onto leaf.

PMID- 16901630
TI  - Solid waste from leather industry as adsorbent of organic dyes in aqueous-medium.
AB  - The industrial tanning of leather usually produces considerable amounts of
      chromium-containing solid waste and liquid effluents and raises many concerns on
      its environmental effect as well as on escalating landfill costs. Actually, these
      shortcomings are becoming increasingly a limiting factor to this industrial
      activity that claims for alternative methods of residue disposals. In this work,
      it is proposed a novel alternative destination of the solid waste, based on the
      removal of organic contaminants from the out coming aqueous-residue. The
      adsorption isotherm pattern for the wet blue leather from the Aurea tanning
      industry in Erechim-RS (Brazil) showed that these materials present high activity
      on adsorbing the reactive red textile dye as well as other compounds. The
      adsorbent materials were characterized by IR spectroscopy and SEM and tested for
      the dye adsorption (reactive textile and methylene blue dyes). The concentrations
      of dyes were measured by UV-vis spectrophotometry and the chromium extraction
      from leather waste was realized by basic hydrolysis and determined by atomic
      absorption. As a low cost abundant adsorbent material with high adsorption
      ability on removing dye methylene blue (80mgg(-1)) and textile dye reactive red
      (163mgg(-1)), the leather waste is revealed to be a interesting alternative
      relatively to more costly adsorbent materials.

PMID- 16901631
TI  - Solubilisation of chlorinated solvents by cyclodextrin derivatives: a study by
      static headspace gas chromatography and molecular modelling.
AB  - The capacity of alpha-cyclodextrin (alpha-CD) and four beta-cyclodextrins (beta
      CDs) in reducing the volatility of volatile organic compounds (VOCs) and
      particularly carbon tetrachloride (CT), chloroform (TCM) and dichloromethane
      (DCM) is investigated by using static headspace gas chromatography (HSGC). The
      experiments allowed the determination of Henry's law constant (H(c)) in absence
      and in presence of cyclodextrins (CDs). The use of CDs may lead to a reduction of
      95% of the Henry's law constant for some VOCs. The association constants of the
      inclusion complexes formed between CDs and the three guests are determined using
      a new method involving an algorithmic treatment bringing the shortening of
      experimental time required for the determination of the stability constant. The
      complementarities of the host and the guest are investigated by molecular
      modelling. The complexation energies obtained are in good agreement with the
      experimental formation constants. Furthermore, this study shows the effectiveness
      of CDs in trapping pollutants and reducing their volatility in the viewpoint of
      pollution prevention.

PMID- 16901632
TI  - Microwave remediation of soil contaminated with hexachlorobenzene.
AB  - This study describes the remediation of hexachlorobenzene (HCB) contaminated
      soils by microwave (MW) radiation in a sealed vial. When powdered MnO2 was used
      as MW absorber, a complete removal of HCB was obtained with 10 min MW by the
      addition of H2SO4 (50%). But no significant decomposition was observed by the
      addition of NaOH (10 mol/L) or H2O in the same conditions. In contrast, when
      powdered Fe was used instead of MnO2, the difference of HCB removals between
      H2SO4 and NaOH were not obvious. It is noteworthy that more than 95% removal was
      achieved in any case when the sole aqueous solution of H2SO4, NaOH, H2O or Na2SO4
      was added without MnO2 or Fe. As a result, it is possible that water itself
      contained in the damp soil may act as MW absorber and remediate the contaminated
      soil without addition of any other MW absorbers. Gas chromatograph/mass spectrum
      (GC/MS) analysis detected no intermediates in all the processes. The
      decomposition mechanism of HCB by MW radiation was suggested as the binding of
      HCB and soil. Whatever fragments formed from HCB by heat were tightly bound to
      the soil, making it impossible to extract them out. In the end, treatment of
      practical HCB contaminated soil by MW reduced HCB from 55.8 mg/kg to 0.91 mg/kg.

PMID- 16901633
TI  - Influence of tone duration and intertone interval on the discrimination of
      frequency contours in a macaque monkey.
AB  - Behavioral studies have shown that non-human primates can categorically
      discriminate descending from ascending frequency steps in sequences of pure
      tones. Here we show that the performance of a long-tail macaque remains stable in
      such a task when the silent interval between the tones of a frequency step is
      varied between 0 and 1100 ms. Our finding suggests that: (1) some monkeys can
      keep frequency-specific information in their short-term memory for periods >1s,
      which can be used to make categorical decisions on the direction of frequency
      steps, and that (2) their ability to categorize the direction of frequency steps
      may be more similar to humans than previously assumed.

PMID- 16901634
TI  - The effect of response uncertainty on illusory biases of perception and action.
AB  - When task requirements were known in advance, Glazebrook et al. [C.M. Glazebrook,
      V.P. Dhillon, K.M. Keetch, J. Lyons, E. Amazeen, D.J. Weeks, D. Elliott,
      Perception-action and the Muller-Lyer illusion: amplitude or endpoint bias?, Exp.
      Brain Res. 160 (2005) 71-78.] demonstrated that perceptual biases associated with
      the Muller-Lyer illusion resulted from a misperception of figure extent, while
      manual aiming biases resulted from a misperception of vertex position. In this
      study, we examined the degree to which prior knowledge of task requirements
      influenced how participants coded visual-spatial information associated with
      Muller-Lyer configurations. Specifically, we investigated how illusory biases are
      affected when uncertainty exists as to whether participants will be required to
      make a perceptual-cognitive decision about the length of a figure or complete a
      rapid aiming movement to a figure vertex. Although aiming movements were
      completed in a similar manner regardless of the prior knowledge condition,
      perceptual biases were associated with a misperception of extent when the task
      was known and a misperception of both extent and position when the task was
      unknown. These findings indicate that people are flexible in the manner in which
      they code visual-spatial information.

PMID- 16901635
TI  - The 196G/A (val66met) polymorphism of the BDNF gene is significantly associated
      with binge eating behavior in women with bulimia nervosa or binge eating
      disorder.
AB  - The brain-derived neurotrophic factor (BDNF) is involved not only in promoting
      neuronal outgrowth and differentiation, synaptic connectivity and neuronal
      repair, but also in modulating eating behavior. Since genetic factors likely
      contribute to the biological vulnerability to bulimia nervosa (BN) and binge
      eating disorder (BED), we investigated whether the functional 196G/A single
      nucleotide polymorphism (SNP) of the BDNF gene was associated to BN and/or BED or
      to some phenotypic aspects of the disordered eating. Two hundred and ten
      Caucasian women (126 with BN, 84 with BED and 121 healthy controls) participated
      into the study. No significant differences were found in the frequencies of the
      196G/A variants of the BDNF gene among patients with BN or BED and healthy
      controls. In both BN and BED groups, subjects carrying the 196A/A genotype
      exhibited a weekly frequency of bingeing and a severity of binge eating (as
      assessed by the Bulimia Investigation Test Edinburgh) significantly higher than
      those with the 196A/G and 196G/G genotypes. These results suggest that the 196G/A
      SNP of the human BDNF gene does not contribute to the genetic susceptibility to
      BN and BED, but may predispose those patients to a more severe binge eating
      behavior.

PMID- 16901636
TI  - Reduction of cerebral infarct size by the AT1-receptor blocker candesartan, the
      HMG-CoA reductase inhibitor rosuvastatin and their combination. An experimental
      study in rats.
AB  - Our purpose was to test the impact of single and/or combined treatment with the
      AT(1)-receptor blocker candesartan and the HMG-CoA reductase inhibitor
      rosuvastatin on infarct size and neuroscore in transient cerebral ischemia in
      rats. L-NAME was used to test whether any potential effect was due to activation
      of endothelial nitric oxide synthase (eNOS). Therefore, the middle cerebral
      artery was occluded for 1 h (MCAO) followed by 7 days reperfusion. Rats received
      candesartan 2h before and daily after MCAO (pretreatment) or daily after MCAO
      (posttreatment); rosuvastatin was given daily for 7 days before MCAO without or
      with candesartan pre- and posttreatment. In addition, candesartan and
      rosuvastatin were combined with L-NAME. Infarct size and neuroscore at day 7 were
      compared to those of controls. As result, compared to controls (109+/-12 mm(3))
      infarct size with candesartan (pretreatment: 21+/-5 mm(3); posttreatment: 68+/-29
      mm(3); P<0.05) or rosuvastatin (69+/-14 mm(3); P<0.05) was smaller. Combined
      treatment also reduced infarct size (pretreatment: 37+/-15 mm(3); posttreatment
      57+/-20mm(3); P<0.05); but there was no benefit of combined treatment over
      candesartan pretreatment alone. Compared to controls (2.08+/-0.28) only
      candesartan pretreatment and combined treatment improved the neuroscore (0.97+/
      0.05, 1.10+/-0.33; P<0.05). L-NAME abolished the reduction in infarct size and
      improvement in neuroscore. In conclusion, both, candesartan or rosuvastatin
      treatment alone reduced infarct size in transient cerebral ischemia, and the best
      result was achieved with candesartan pretreatment. Combined treatment was
      superior to rosuvastatin alone, but not to candesartan. The therapeutic benefit
      of both agents was at least in parts mediated by eNOS-activation.

PMID- 16901637
TI  - Step initiation in Parkinson's disease: influence of initial stance conditions.
AB  - In this study, we investigated how the size of preparatory postural adjustments
      prior to step initiation, and step length and velocity depend on initial stance
      width in patients with Parkinson's disease (PD) both in the ON and OFF levodopa
      states and in healthy elderly subjects. Twenty-one subjects with idiopathic PD
      and 24 age-matched healthy control subjects took two steps starting with feet on
      a two-plate force-platform, from either narrow or wide stance width. We measured
      how the magnitude of anticipatory postural adjustments (APA) and step
      characteristics scaled with stance width. Results showed that preparation for
      step initiation from wide stance was associated with a larger lateral and
      backward center of pressure (CoP) displacement than from narrow stance. Velocity
      and length of the first step were also sensitive to initial stance conditions,
      probably in relation with the differences in the corresponding APA. On the
      contrary, the duration of APA was not significantly affected by initial stance
      width, but it was longer in PD compared to healthy subjects, and speeded up by
      levodopa. Although subjects with PD did scale up the size of their APA with
      stance width, they had much more difficulty initiating a step from a wide stance
      than from a narrow stance, as shown by the greater differences from control
      subjects in the magnitude of the APA. Our results support the hypothesis that PD
      subjects maintain a narrow stance as a compensation for their inability to
      sufficiently increase the size of their lateral APA to allow fast step initiation
      in wide stance.

PMID- 16901638
TI  - Delayed beta synchronization after movement of the more affected hand in
      essential tremor.
AB  - To investigate the pathomechanism of parkinsonian tremor (PT) and essential
      tremor (ET) by studying the correlation between tremor asymmetry and post
      movement beta synchronization (PMBS) of the human EEG. We recorded the EEG of 10
      patients with ET, 10 patients with Parkinson's disease and 10 controls. Subjects
      pressed an on-off switch in a self-paced manner with the thumb of their less (T+)
      and more (T++) tremulous hand. After digitalization of the EEG from the Cz, C3,
      C4 electrodes the movement reactive beta frequency, its maximum peak power value
      and its latency triggered to movement offset were determined. In ET tremor
      intensity did not influence the power of PMBS, however it was significantly
      delayed after the movement of the more tremulous hand. In Parkinson's disease
      after the movement of the more tremulous hand PMBS power was decreased, but it
      was not delayed. In controls the side of movement had no effect on the power and
      latency of the PMBS. The neuronal mechanisms underlying PMBS generation are
      differently affected in essential tremor and Parkinson's disease. The increase of
      PMBS latency after movement of the more affected hand in ET indicates possible
      cortical mechanisms in essential tremor generation.

PMID- 16901640
TI  - Hypoxia and reoxygenation increased BACE1 mRNA and protein levels in human
      neuroblastoma SH-SY5Y cells.
AB  - Ischemic cerebrovascular diseases, usually involved in hypoxia and reoxygenation,
      have been reported to increase the risk of dementia such as Alzheimer's disease
      (AD). beta-site amyloid protein precursor (APP)-cleaving enzymes (BACE1) have
      been identified to participate in the secretion of beta-amyloid peptides (Abeta),
      and its expressive alteration would contribute to the AD neuropathology. We have
      investigated the effect of hypoxia (0% O(2), 24h) and reoxygenation (0h, 12h and
      24h after 24h hypoxia) on BACE1 mRNA and protein levels in human neuroblastoma SH
      SY5Y cells. At the same time, we also examined the effect of hypoxia and
      reoxygenation on APP mRNA and protein levels. We demonstrated that hypoxia and
      reoxygenation did not alter APP mRNA and protein level, However compared to those
      of controls, BACE1 mRNA levels were up-regulated by 31.5% (P=0.028) and 35.1%
      (P=0.005) at 12h and 24h and the protein levels increased to 22%(P=0.021), 42%
      (P=0.000) and 51.5% (P=0.000) at 0h, 12h and 24h after reoxygenation,
      respectively. Thus by up-regulating of BACE1 mRNA and protein level in the
      neuronal cell, hypoxia may be a linkage in the pathophysiology between
      cerebravascular diseases and AD.

PMID- 16901639
TI  - Central ghrelin acts as an anti-dipsogenic peptide in chicks.
AB  - The aim of this study was to look at whether ghrelin has an anti-dipsogenic
      effect, as seen in the eel, when administered centrally in neonatal chicks.
      Intracerebroventricular (ICV) injection of chicken ghrelin inhibited water intake
      (WI) in chicks under both ad libitum and 17-h water-deprived drinking conditions
      at doses ranging from 0.01 to 0.1nmol/chick. This inhibitory effect was observed
      when 0.1nmol of rat ghrelin was injected. On the other hand, 0.1nmol des-acyl rat
      ghrelin did not reduce WI. To examine the mechanism underlying the effect of
      ghrelin on WI, chicken B-type (or brain) natriuretic peptide (BNP), an anti
      dipsogenic peptide in mammals, was injected at doses ranging from 0.1 to
      1nmol/chick. BNP did not affect WI in chicks under both normal and water-deprived
      drinking conditions. These findings indicate that ghrelin acts as an anti
      dipsogenic peptide through the GHS receptor in the chicken.

PMID- 16901641
TI  - Reduced short latency afferent inhibition in diffuse axonal injury patients with
      memory impairment.
AB  - The present study used short interval intracortical inhibition (SICI),
      intracortical facilitation (ICF), and short latency afferent inhibition (SAI) to
      evaluate motor cortex excitability in 16 diffuse axonal injury (DAI) patients
      with memory impairment and compared the data with those of 16 healthy controls.
      SAI was reduced in patients compared with controls (92+/-12 versus 39+/-11% of
      the test size; p<0.0001, unpaired t-test). DAI patients tended to have a high
      resting motor threshold (RMT) and less pronounced SICI and ICF than controls, but
      these differences were not significant. A single oral dose (3mg) of donepezil, an
      acetylcholinesterase inhibitor that is commonly used to treat Alzheimer's disease
      (AD), improved SAI in DAI patients with wide individual variations that ranged
      from an increase of 77-18% of test size. These findings suggest that measuring
      SAI may provide a means of probing the integrity of cholinergic networks in an
      injured human brain.

PMID- 16901642
TI  - alpha-synuclein from platelets is not phosphorylated at serine 129 in Parkinson's
      disease and multiple system atrophy.
AB  - Parkinson's disease (PD) and multiple system atrophy (MSA) are characterized
      pathologically by inclusions in the brain containing alpha-synuclein, which is
      phosphorylated at serine 129. alpha-Synuclein is present not only in the brain
      but also in platelets; platelets have previously been used to study mitochondrial
      function in PD. We undertook to determine whether alpha-synuclein extracted from
      platelets of patients with PD and MSA is phosphorylated at serine 129 and could
      be used as a peripheral marker of these disorders. Immunoblots indicated that
      platelet alpha-synuclein is not phosphorylated at serine 129 in PD and MSA.

PMID- 16901643
TI  - Identification and mRNA expression of Ogdh, QP-C, and two predicted genes in the
      postnatal mouse brain.
AB  - By fluorescent differential display, we identified six transcripts (CAPS2/Cadps2,
      Cdh22, b1402, c1502, d1401, and d1501) that showed the differential expression
      patterns during the postnatal development of the mouse cerebellum. We further
      analyzed the latter four transcripts whose cellular localizations in developing
      mouse brains have not been studied. In the postnatal cerebellum, clones c1502 and
      d1501 were transiently up-regulated; clone b1402 was up-regulated; and clone
      d1401 remained relatively constant. Sequence analysis revealed that d1401 and
      c1502 were derivatives of Ogdh (oxoglutarate dehydrogenase) and QP-C (ubiquinol
      cytochrome c reductase complex ubiquinone-binding protein), respectively.
      Moreover, b1402 and d1501 were identified as transcripts of a predicted gene
      (4933409K07Rik) and a novel EST, respectively. b1402 and d1501 were abundantly
      present in the cerebellum, whereas c1502/QP-C and d1401/Ogdh were widely
      distributed in various mouse tissues. In the postnatal mouse brain, moderately
      high mRNA levels of b1402 were restricted to the olfactory bulb, striatum,
      cerebral cortex (layers II-III and VI), hippocampus (dentate granule cells), and
      cerebellum (granule cells). c1502/QP-C mRNA was localized at high levels in the
      olfactory bulb, cerebral cortex, hippocampus, thalamus (anterodorsal nucleus,
      parafacicularis nucleus), tegmentum (red nucleus), cerebellum (Purkinje and
      granule cells), and pons (pontine nucleus, reticulotegmental nucleus, trapezoid
      body, vestibular nucleus). High mRNA levels of d1401/Ogdh were observed in the
      olfactory bulb, hippocampus, cerebellum, and pons, whereas those of d1501 were
      detected in the granule cells of the olfactory bulb, dentate gyrus, and
      cerebellum.

PMID- 16901644
TI  - Imaging gene-substance interactions: the effect of the DRD2 TaqIA polymorphism
      and the dopamine agonist bromocriptine on the brain activation during the
      anticipation of reward.
AB  - Dopamine is known as the main neurotransmitter modulating the activation of the
      reward system of the brain. The DRD2 TaqIA polymorphism is associated with
      dopamine D2 receptor density which plays an important role in the context of
      reward. Persons carrying an A1 allele have a lower D2 receptor density and a
      higher risk to show substance abuse. The present study was designed to
      investigate the influence of the DRD2 TaqIA polymorphism and the selective D2
      receptor agonist bromociptine on the activation of the reward system by means of
      functional magnetic resonance imaging (fMRI). In a double-blind crossover study
      with 24 participants we found an increase of reward system activation from
      placebo to bromocriptine only in subjects carrying the A1 allele. Furthermore,
      only A1 carrier showed an increase of performance under bromocriptine. The
      results are interpreted as reflecting a specific sensitivity for dopamine
      agonists in persons carrying an A1 allele and may complement actual data and
      theories of the development of addiction disorders postulating a higher genetic
      risk for substance abuse in carrier of the A1 allele.

PMID- 16901645
TI  - Differential sensitivity of three experimental pain models in detecting the
      analgesic effects of transdermal fentanyl and buprenorphine.
AB  - This is the first randomized controlled trial that tests the analgesic efficacy
      of transdermally delivered opioids in healthy volunteers and that assesses the
      sensitivity of different experimental pain tests to detect analgesia in this
      setting. Transdermal application of the full agonist fentanyl (TDF: 12.5 or 25
      microg/h) and the partial agonist buprenorphine (TDB: 35 microg/h) was compared
      in three experimental models of acute pain (heat pain, painful electrical
      stimulation, cold pressor) in a double-blind, randomized, placebo-controlled, 4
      arm crossover study with 20 healthy subjects (15 men, 5 women). Patches were
      administered for 72 h and pain levels measured at baseline and 24 and 72 h, with
      an 11-day wash-out. The cold pressor test was most sensitive to analgesic
      effects, with significant reductions in area under the pain intensity curve for
      all active compounds at 24 h (average reductions: 14% TDF 12.5 microg/h, 35% TDF
      25 microg/h, 43% TDB 35 microg/h). There were significant increases in heat pain
      threshold for TDF 25 microg/h and TDB 35 microg/h. Painful electrical stimulation
      failed to demonstrate an analgesic effect. The magnitude of analgesia in the cold
      pressor model showed some correlation with TDF dosage and comparable effects for
      the full agonist fentanyl and the partial agonist buprenorphine. We conclude that
      the cold pressor test was most sensitive to analgesic effects in healthy subjects
      and that a transdermal dose of 12.5 microg/h fentanyl achieved significant pain
      reduction compared with placebo. Subjects experienced opioid-typical AEs
      including dizziness, nausea and vomiting. No serious AEs occurred.

PMID- 16901646
TI  - Are we "fear-avoidant"?

PMID- 16901647
TI  - Amino acid release at the spinomedullary junction after inflammation of the TMJ
      region in male and female rats.
AB  - Temporomandibular joint (TMJ) disorders are painful conditions that are more
      prevalent in women than men. This study tested the hypothesis that acute
      inflammation of the TMJ region evoked sex-related changes in amino acid
      transmitter concentrations at the trigeminal subnucleus/upper cervical cord
      (Vc/C2) junction, the major terminal zone for TMJ sensory afferents.
      Microdialysis samples were collected in male, intact and ovariectomized (OvX)
      female rats after injection of mustard oil into the TMJ region (TMJ-MO) under
      barbiturate anesthesia. Males displayed increases in glutamate, aspartate and
      serine at 5 min and secondary increases 40-45 min after TMJ-MO. Intact and OvX
      females given low dose estrogen (LE2) displayed increases in glutamate, aspartate
      and serine at 5 min but no secondary increase at 40 min, while OvX females given
      high dose estrogen (HE2) revealed no increases after TMJ-MO. Glycine increased 20
      min after TMJ-MO in males and cycling females, but not in OvX rats. Perfusion of
      high potassium through the probe evoked similar increases in glutamate, aspartate
      and glycine in all groups. In separate experiments, perfusion of the glutamate
      aspartate reuptake inhibitor, L-trans-2,4-pyrrolidine dicarboxylate (PDC),
      through the probe caused a prompt elevation in glutamate that was significantly
      greater in HE2 than LE2 females or males. These results suggested sex hormone
      status affects glutamatergic neurotransmission at the Vc/C2 junction by acting,
      in part, through modulation of glutamate reuptake. Altered amino acid transmitter
      release and/or availability at the Vc/C2 junction may contribute to differential
      processing of sensory input from the TMJ region in males and females.

PMID- 16901648
TI  - The effect of a parenteral ivermectin/closantel injection on the growth and
      reproductive development of early immature Fasciola hepatica in cattle.
AB  - Sixteen calves approximately 6 months old were each infected with 500
      metacercariae of Fasciola hepatica. Thirty-two days later they were weighed and
      divided into two groups, and on day 35 all calves in one of the groups were
      injected subcutaneously with an ivermectin/closantel combination. Both groups
      were sacrificed between days 70 and 72 to enable counting and examination of the
      flukes recovered from the bile ducts. Eggs released by the flukes were collected
      for incubation, hatching and estimation of egg viability. Flukes were counted,
      flat-fixed in 70% ethanol, stained with catechol and carmine and measured. The
      reproductive organs, namely testis, vitelline glands, ovary and uterus, were
      examined and scored on a 0-3 scale according to their state of development. This
      was visually assessed on the basis of size, distribution and staining density of
      their constituent tissues and the abundance of eggs in the uterus. A
      representative sample of flukes from each animal was fixed in formalin for
      histological sectioning to enable more detailed examination of the reproductive
      structures. Treatment of the immature flukes reduced the population in cattle by
      42.6% as compared with the controls and as a result of the stunting effect due to
      the presence of closantel during early development the size of treated flukes was
      reduced by 43.9%. A bimodal pattern of size and reproductive score was also
      observed in flukes from treated cattle, suggesting that the stunting effect on
      individual flukes differed depending on whether or not they had gained access to
      the bile ducts or were still migrating in the hepatic parenchymal tissue at the
      time of drug exposure with the effect being greater once the fluke had gained
      access to the bile ducts. The mean reproductive score for untreated flukes was
      8.76 and for treated flukes 5.64, a 35.6% reduction. This difference was highly
      significant (p<0.001). Egg shedding from treated flukes was significantly less
      than that from controls (p<0.05), but there were no differences in hatchability,
      suggesting that whilst drug treatment reduced the energy supply available for
      gametogenesis/oogenesis, it did not induce functional defects in the gonads or
      accessory reproductive organs. Histological examination confirmed that there was
      a reduction in development of testes, ovaries and vitellaria in treated flukes,
      with a consequent reduction in egg production. In the treated flukes, early
      spermatogonia and oogonia were the predominant cell types in the testes and
      ovary, whilst undifferentiated stem cells were abundant in the vitelline
      follicles. In untreated flukes, cells representing more advanced stages in
      gametogenesis and vitellogenesis predominated in the respective organs. It is
      likely that this inhibition of gametogenesis and vitellogenesis was caused by the
      effects of closantel treatment on intermediary metabolism in the flukes. Clearly
      these effects were evident even at a relatively early stage of fluke growth, and
      because of the impact on egg output may have epidemiological importance in
      addition to the reduction in fluke numbers.

PMID- 16901649
TI  - Evaluation of antioxidant status and oxidative stress in cattle naturally
      infected with Theileria annulata.
AB  - To assess the antioxidant status and oxidative stress in bovine theileriosis due
      to Theileria annulata blood samples were collected from 35 clinically affected
      cattle referred to Veterinary Teaching Hospital, School of Veterinary Medicine,
      Urmia University, Urmia, Iran. Complete blood count, piroplasm parasitemia
      percentage, erythrocyte glutathione peroxidase, superoxide dismutase, catalase
      and glucose-6-phosphate dehydrogenase activities, malondialdehyde concentration,
      osmotic fragility test and median corpuscular fragility were determined and the
      results were compared with those of 50 healthy controls. Of 35 affected cattle,
      12 (34.28%) had severe anemia and 23 had mild to moderate anemia and parasitemia
      varied from 5 to 40%. The activities of erythrocyte glutathione peroxidase,
      superoxide dismutase and glucose-6-phosphate dehydrogenase were significantly
      lower (P<0.0001) and the activity of catalase was significantly higher in the
      affected cattle than in healthy ones (P<0.001). Malondialdehyde concentration in
      erythrocytes of affected cattle was significantly more than those of healthy
      cattle (P<0.001). The affected cattle showed increased fragility of erythrocytes,
      so that median corpuscular fragility (MCF) in affected group was significantly
      lower than those of healthy group (P<0.0001). Median corpuscular fragility showed
      a positive correlation with the severity of parasitemia (r=0.81, P<0.0005) and a
      negative correlation with the activities of GSH-Px (r=-0.78, P<0.0001), SOD (r=
      0.71, P<0.0005), catalase (r=-0.53, P<0.018) and G6PD (r=-0.58, P<0.0005). The
      results of this study suggest that oxidative damage to RBCs may contribute to the
      pathogenesis of anemia in bovine theileriosis.

PMID- 16901650
TI  - Inhibitory effects of lanthanum chloride on extracellular matrix in injury
      tissues of rats.
AB  - The propose of the present study is to investigate the effects of lanthanum
      chloride (LaCl(3)), a rare earth compound, on extracellular matrix molecules in
      rat wound tissues, hoping to provide a clue for further study in reducing
      excessive extracellular matrix formation in trauma and burn, as well as in
      fibrous disorders. In order to elucidate its action mechanism, we investigated
      its effects on fibroblast apoptosis, intracellular calcium, collagen synthesis
      and expression, and fibronectin mRNA expression. We found that treatment with
      0.25 ml of 50 mM (1.5mg/injection) LaCl(3) for three consecutive days induced
      fibroblast apoptosis and inhibited collagen synthesis and expression. Comparing
      to control, at day 14 after wounding, apoptosis and the level of intracellular
      calcium in wound tissues were significantly increased, but at day 28 after
      wounding, apoptosis was not continually increased and gradually became normal. In
      contrast, the amount of (3)H-proline incorporation and the expression of type I
      and III collagen decreased at days 14 and 28 after wounding by LaCl(3)-treatment.
      The expression of fibronectin mRNA was not significant changed at days 14 and 28
      after-wounding by LaCl(3)-treatment as compared to the control. The results
      suggest that LaCl(3) may reduce the extracellular matrix formation at certain
      concentrations during wound healing and be worth further study as an anti-fibrous
      agent. Because lanthanides have been used to clinical treatment with
      antibacterial agents in burn, it may be more suitable for the treatment of severe
      burn.

PMID- 16901651
TI  - Evidence for the link between healing time and the development of hypertrophic
      scars (HTS) in paediatric burns due to scald injury.
AB  - The relationship between burn depth, healing time and the development of
      hypertrophic scarring (HTS) is well recognised by burn surgeons but is seldom
      mentioned in the published literature. We studied 337 children with scalds whose
      scars were monitored for up to 5 years. Overall HTS rates were found to be: under
      10 days to healing=0%, 10-14 days=8%, 15-21 days=20%, 22-25 days=40%, 26-30
      days=68% and over 30 days=92%. In the conservatively treated group the HTS rates
      are: under 10 days=0%, 10-14 days=2%, 15-21 days=20%, 22-25 days=28%, 26-30
      days=75% and over 30 days=94%. If skin grafting is undertaken there is a much
      higher incidence of HTS in the 10-14 days group: 10-14 days=33%, 15-21 days=19%,
      22-25 days=54%, 26-30 days=64% and over 30 days=88%. We conclude that there is a
      low risk of HTS formation in scalds healed before 21 days, and that surgery
      should be reserved for scalds likely to take more than 21 days to heal.

PMID- 16901652
TI  - Scalding from a hospital hot water supply: are we risk in the work place?

PMID- 16901653
TI  - Clinical significance of leukocyte infiltrative response in deep wound of
      patients with major burns.
AB  - OBJECTIVE: To investigate the time course of infiltrated leukocytes and the
      subpopulations of infiltrated lymphocytes in deep wounds, and their relationship
      with injury severity in seriously burned patients. METHODS: Six patients with
      major burns were enrolled in the study. Specimens were taken from deep partial
      thickness burn wounds of all patients at 3 days, 1 week, 2 weeks and 3 weeks
      after burn. The appearance time and cellular components of infiltrated leukocyte
      zone in the burn wound were evaluated by histological and immunohistochemistry
      examination with lymphocyte monoclonal antibodies. RESULTS: The infiltrated
      leukocyte zone of burn wound formed 1-2 weeks after burn. The more severe the
      degree of injury (including burn area, depth and combined injuries) was, the
      later the infiltrated leukocyte zone appeared. The infiltrated cells mainly
      consisted of polymorphonuclear leukocytes (PMN) during the early period after
      burn while macrophages and lymphocytes appeared later. There were some changes of
      the T lymphocyte subsets and their activation degree in the burn wound.
      CONCLUSION: The changes of infiltrated leukocyte zone of wound following burns
      were closely related to the injury severity, and represented alteration of the
      anti-infection ability and immune rejection of local wound. These results provide
      important evidence for appropriate wound treatment and prolonging the survival of
      skin allograft.

PMID- 16901655
TI  - Advances in Runx2 regulation and its isoforms.
AB  - During the last 10 years, we have witnessed major progress in skeleton biology.
      Runx2 is an accepted transcription factor essential for osteoblast development
      from mesenchymal stem cells and maturation into osteocytes and organize crucial
      events during bone formation. Alternations in Runx2 expression levels are
      associated with skeletal diseases. In vitro and in vivo studies have reported
      that multiple integrated complex path ways (such as Wnt/LRP5/beta-catenin,
      BMP/Smads, 1, 25-(OH)2-vitaminD3/VDR/VDRE pathway, etc.) and several regulatory
      proteins (such as Msx2, Dlx5, Twists, etc.) play critical roles in modulating
      Runx2 gene expression, activity, and the subsequent bone formation. These
      findings provide novel insights through controlling osteoblast differentiation to
      treat osteoporosis or other bone diseases with altered bone mass by stimulating
      Runx2 expression. Further studies have shown that expression of RUNX2 is
      initiated from two promoters, the distal P1 promoter and the proximal P2
      promoter. The alternative use of promoters gives rise to the genesis of two major
      protein isoforms with distinct amino termini, named as Runx2-TypeI and Runx2
      TypeII. Here, we also review a complex spatio-temporal pattern of two major
      isoforms expressions and their possible function differences in skeleton
      development.

PMID- 16901654
TI  - Respondent-driven sampling in the recruitment of illicit stimulant drug users in
      a rural setting: findings and technical issues.
AB  - Increasingly, respondent-driven sampling (RDS) is being applied to study not-in
      treatment users of illicit drugs. Although RDS has been successfully applied in
      recruiting active users in densely-populated, metropolitan areas, its utility
      with hidden populations in rural areas has yet to be determined. This study
      critically evaluates the sample of not-in-treatment, illicit stimulant drug users
      (n=249) recruited from the application of RDS in three rural counties in west
      central Ohio. The findings of this study largely support the results of earlier
      studies in urban areas and suggest that RDS is a useful method of sampling hidden
      drug using populations in less densely populated rural areas. Some limitations of
      RDS are also discussed.

PMID- 16901656
TI  - The first international meeting on V617F JAK2 mutation and its relevance in
      Philadelphia-negative myeloproliferative disorders.
AB  - The first international meeting on V617F JAK2 mutation in myeloproliferative
      disorders (MPD) was held by the PV-Nord group on behalf of the French Society of
      Hematology and Paris 13 University on November 18, 2005, in Paris (France).
      Twelve speakers, including representatives of the three European groups who
      discovered the V617F JAK2 mutation and international experts in the field of
      Philadelphia-negative MPD, presented original biological and clinical data that
      allow better insight in the relevance of V617F JAK2 mutation in the pathogenesis
      and management of those diseases. The role of V617F JAK2 in cytokine receptors
      trafficking and signaling was described. Follow-up of transgenic mice expressing
      V617F JAK2 showed that they develop typical features of myelofibrosis.
      Comparisons of JAK2 mutational status to clonality of hematopoiesis in essential
      thrombocythemia on the one hand, and to activation of transcription factors in
      myelofibrosis with myeloid metaplasia on the other hand, suggest that JAK2
      mutation could be a second genetic event in a subset of patients. Alternatively,
      other gene mutation(s) have to be found to explain the development of V617F
      negative MPD. In large series of MPD patients presented, clinical characteristics
      of mutated and non-mutated patients were found different. Finally, the place of
      V617F JAK2 testing in the diagnosis and management of MPD was discussed.

PMID- 16901657
TI  - [Cytogenetics and molecular genetics in myelofibrosis with myeloid metaplasia and
      polycythemia vera].
AB  - Myelofibrosis with myeloid metaplasia (MMM) is a rare myeloproliferative disorder
      (MPD) characterized by clonal proliferation of hematopoietic progenitors. 40-50%
      of karyotypes on blood (or more rarely on bone marrow) revealed at least one
      abnormality: 30% at diagnosis and 90% in blastic transformation phase. A minority
      of patients with newly diagnosed polycythemia vera (PV) presented chromosomal
      abnormalities in their myeloid cells. The most frequent visible alteration in MMM
      and PV is a 20q deletion, also characterized in other MPDs and myeloid
      malignancies. Among other chromosomal changes, deletion 13q is more common in MMM
      than in other MPDs, trisomy 9 and 9p alterations appear more frequent in PV.
      Cytogenetic studies have disclosed cryptic anomalies and pointed out the high
      frequency of 9p alterations. JAK2 (V617F) mutation was found in almost all PV
      patients and near half of MMM patients. This molecular abnormality takes an
      increased importance in the knowledge of the physiopathology of MPDs,
      particularly in PV and also in prognosis of MMM patients.

PMID- 16901658
TI  - Characterization of the porcine alpha interferon multigene family.
AB  - The availability of data on the pig genome sequence prompted us to characterize
      the porcine IFN-alpha (PoIFN-alpha) multigene family. Fourteen functional PoIFN
      alpha genes and two PoIFN-alpha pseudogenes were detected in the porcine genome.
      Multiple sequence alignment revealed a C-terminal deletion of eight residues in
      six subtypes. A phylogenetic tree of the porcine IFN-alpha gene family defined
      the evolutionary relationship of the various subtypes. In addition, analysis of
      the evolutionary rate and the effect of positive selection suggested that the C
      terminal deletion is a strategy for preservation in the genome. Eight PoIFN-alpha
      subtypes were isolated from the porcine liver genome and expressed in BHK-21
      cells line. We detected the level of transcription by real-time quantitative RT
      PCR analysis. The antiviral activities of the products were determined by WISH
      cells/Vesicular Stomatitis Virus (VSV) and PK 15 cells/Pseudorabies Virus (PRV)
      respectively. We found the antiviral activities of intact PoIFN-alpha genes are
      approximately 2-50 times higher than those of the subtypes with C-terminal
      deletions in WISH cells and 15-55 times higher in PK 15 cells. There was no
      obvious difference between the subtypes with and without C-terminal deletion on
      acid susceptibility.

PMID- 16901659
TI  - Sporulation-specific expression of the yvgW (cadA) gene and the effect of
      blockage on spore properties in Bacillus subtilis.
AB  - The yvgW gene of Bacillus subtilis has been reported to encode a product which
      resembles CPx-type ATPase having a function related to Cd2+ and Zn2+ resistance
      through efflux of this metal. We recently showed that yvgW gene product is also
      important for sporulation in B. subtilis. The present study was focused on the
      functional characterization of yvgW in the sporulation process of B. subtilis.
      The analysis of yvgW expression showed that a significant expression took place
      during the late stage of sporulation (T5-T8). The deletion of spoIIAC and spoIIGB
      genes, encoding for sigmaF and sigmaE, respectively, resulted in the complete
      elimination of yvgW-lacZ expression while the deletion of the spoIIIG coding for
      sigmaG decreased the yvgW-lacZ expression to only 37% that of the wild type
      level. In contrast, the deletion of spoIVCB gene coding for sigmaK had no
      significant effects on the yvgW-lacZ expression. Transcription initiation site of
      yvgW during sporulation was determined by 5'-RACE-PCR, indicating that -10 and 
      35 sequences exhibited very good homology with the consensus sequences recognized
      by RNA polymerase containing sigmaE. Moreover, through the construction of
      yvgWDelta537-1351::spc, yvgW mutant cells were investigated for their spore
      properties, such as their resistance profiles against heat, chloroform and
      lysozyme, pointing out that spores of the mutant cells showed high sensitivity to
      heat and chloroform, but resistance to lysozyme. The level of dipicolinic acid
      was also significantly reduced to approximately 63% in yvgW spores as compared to
      wild type spores. Furthermore, the analyses of the nutrition-specific germination
      and outgrowth characteristics of the null mutant and the wild type cells revealed
      no defect in the initiation of yvgW spore germination but they returned to
      vegetative state more slowly than the wild type spores in minimal medium.

PMID- 16901660
TI  - The attitude of gynecologists in Sao Paulo, Brazil 3 years after the Women's
      Health Initiative study.
AB  - OBJECTIVE: The objective of this study was to evaluate gynecologists' knowledge
      of the WHI study, and its repercussions on their attitudes and practice 3 years
      after publication. DESIGN: A self-administered, anonymous questionnaire
      containing 19 questions was sent to 6000 gynecologists, members of the Sao Paulo
      Society of Obstetrics and Gynecology. RESULTS: The response rate was 24.2% (1453
      completed questionnaires) with a sample error of 2.23% and confidence level of
      95%. Although 95.9% of the respondents were aware of the WHI study, only 24.4%
      knew of all the other studies mentioned (HERS I, HERS II and Million Women
      Study). Although 84.6% stated that the results of the WHI study could not be
      extrapolated to other forms of HT, 23.1% and 25.2%, respectively, stopped
      prescribing CEE or MPA, 63.7% decreased the dose, 55.2% opted for drugs such as
      bisphosphonates, tibolone and SERMS, and 46.3% began to prescribe tranquilizers,
      isoflavone and other natural medications. Moreover, 59.2% agreed that HT should
      be used for only 4-5 years. Prescriptions decreased significantly for all
      indications (p<0.0001). The principal reason for physicians to discontinue HT in
      a patient was increased risk of breast cancer (62.3%), whereas, according to the
      physicians, the most important factor for the patients was fear of HT (80.3%).
      CONCLUSION: A high percentage of gynecologists in this study knew of the WHI
      study and followed its recommendations concerning cardiovascular prevention;
      consequently they changed their management of the treatment of postmenopausal
      women by restricting indications for HT and decreasing its duration of use and
      dose.

PMID- 16901662
TI  - Preparation of uniform biodegradable microparticles using laser ablation.
AB  - In an attempt to prepare uniformly sized biodegradable microparticles for
      controllable drug eluting and targeting characteristics, a novel technique by
      employing ultrashort pulse (USP) laser has been developed. This method involves
      pumping a drug-polymer solution through a small orifice creating a liquid stream.
      A USP laser constantly fires at the stream to cut it into discrete droplets and
      consequently solid particles can be obtained with monodisperse size distribution.
      Through mathematical modeling, volumetric flow rate, orifice size, laser spot
      size, and laser frequency were found as sole factors determining the size profile
      of the resulting microparticles. By choosing appropriate set of variables,
      monosized biodegradable microparticles with wide range of particle size may be
      prepared.

PMID- 16901663
TI  - Preparation and physical characterization of a novel marine oil emulsion as a
      potential new formulation vehicle for lipid soluble drugs.
AB  - Emulsions often contain vegetable oils such as soybean oil. In this study, a 10%
      (w/w) of marine mammal oil emulsion was prepared. The effect of a group of
      emulsifying agents on the stability of the 10% of seal oil emulsion was examined.
      The emulsifying agents studied were hydrogenated castor oil coated with various
      polyoxyethylene derivatives. It was found that 2.5% of HCO-40 resulted in the
      most stable seal oil emulsion. The size of the emulsified droplets defined by
      their diameters was found to be around 240-270 nm. The initial zeta-potential and
      pH value of the emulsion were found to be around -27 mV and 3.5, respectively,
      which decreased over time, to about -31 mV and 2.4, respectively. This is
      believed to be a result of the hydrolysis of triacylglycerides into free fatty
      acids in the emulsion. The effect of various amounts of Crodasinic LS-30, a
      negatively charged surfactant, and Incroqal Behenyl TMS, a positively charged
      surfactant, on the emulsion was investigated. It was shown that Crodasinic LS-30
      had very little effect on the particle size, zeta-potential and pH, while the
      effect of Incroquat Benhenyl TMS was found to be dependent upon the concentration
      of the surfactant used.

PMID- 16901664
TI  - Cellular correlates of age-related endocochlear potential reduction in a mouse
      model.
AB  - Age-related degeneration of cochlear stria vascularis and resulting reduction in
      the endocochlear potential (EP) are the hallmark features of strial presbycusis,
      one of the major forms of presbycusis, or age-related hearing loss (ARHL)
      (Schuknecht, H.F., 1964. Further observations on the pathology of presbycusis.
      Archives of Otolaryngology 80, 369-382; Schuknecht, H.F., 1993. Pathology of the
      Ear. Lea and Febiger, Philadelphia; Schuknecht, H.F., Gacek, M.R., 1993. Cochlear
      pathology in presbycusis. Annals of Otology, Rhinology and Laryngology 102, 1
      16). It is unclear whether there are multiple forms of strial ARHL having
      different sequences of degenerative events and different risk factors. Human
      temporal bone studies suggest that the initial pathology usually affects strial
      marginal cells, then spreads to other strial cell types. While inheritance
      studies support a moderate genetic influence, no contributing genes have been
      identified. Establishment of mouse models of strial ARHL may promote the
      identification of underlying genes and gene/environment interactions. We have
      found that BALB/cJ mice show significant EP reduction by 19 months of age. The
      reduction only occurs in a subset of animals. To identify key anatomical
      correlates of the EP reduction, we compared several cochlear lateral wall metrics
      in BALBs with those in C57BL/6J (B6) mice, which show little EP reduction for
      ages up to 26 months. Among the measures obtained, marginal cell density and
      spiral ligament thickness were the best predictors of both the EP decline in
      BALBs, and EP stability in B6. Our results indicate that the sequence of strial
      degeneration in BALBs is like that suggested for humans. Additional strain
      comparisons we have performed suggest that genes governing strial melanin
      production do not play a role.

PMID- 16901665
TI  - A quantitative analysis of psychometric functions for different auditory tasks in
      gerbils.
AB  - The psychometric function relates the probability of a correct response to the
      variation of a physical stimulus parameter. In many perceptual tasks one point on
      this function is defined by a more or less arbitrary threshold criterion and
      threshold is used to study the effects of various treatments or age. Besides
      threshold, the shape of the psychometric function provides additional
      information. The variability of internal (neural) noise and the sensorineural
      transduction function will affect the shape of the psychometric function and may,
      therefore, reveal important features in the processing of stimulus
      characteristics. Here we analyze the effect of age on psychometric functions from
      gerbils: (A) for the detection of a tone or noise pulse in silence which is
      generally regarded as a measure of cochlear function and (B) for a gap detection
      task, investigating aspects of temporal processing that involve the ascending
      auditory pathway. Our data show that the slope of the psychometric function for
      the detection of tone and noise pulses in silence is independent of age and
      threshold. In contrast, the steepness of the psychometric function is decreased
      in gerbils with impaired temporal resolution. We discuss these observations in
      the context of physiological data from young and old animals.

PMID- 16901666
TI  - Medicinal plants used to induce labour during childbirth in western Uganda.
AB  - Traditional medicine usage in rural Ugandan population for day-to-day health care
      needs is close to 90%. Women and children form the bulk of the people reliant on
      herbal medicine. This study was undertaken to document how ethnomedical folklore
      aids childbirth in rural western Uganda by conducting field surveys, discussions
      and interviews with the resource users (mothers) and health providers
      (traditional birth attendants). Health surveys revealed that over 80% of
      childbirths are conducted at home by using herbal remedies in Bushenyi district.
      Seventy-five plants have been recorded for usage in inducing labour and some of
      these plants may be oxytocic. The dilemma lies in the toxicity levels and the
      unspecified dosages that may threaten the life of the unborn baby and the mother.
      The high population growth rate, high total fertility rate coupled with high
      maternal mortality and morbidity in Uganda calls for rethinking in gendered
      health provision policies and programmes for which herbal medicine integration in
      health care systems seems viable.

PMID- 16901667
TI  - Factors affecting strontium absorption in drownings.
AB  - This study examines the effects of age, gender, a cold water medium versus warm
      water medium, and salinity on strontium levels determined in left ventricular
      blood in drownings. Significant differences in the amount of strontium absorbed
      into the bloodstream (p<0.001) were detected between individuals who drowned in
      fresh water versus those drowning in seawater, and between those drowning in cold
      water versus warm water (p=0.030). However, no significant differences were noted
      in the strontium concentrations of left ventricular blood according to gender or
      age.

PMID- 16901668
TI  - A GC/MS study of the drying of ballpoint pen ink on paper.
AB  - The determination of the age of an ink entry from a questioned document is often
      an essential problem and a controversial issue in forensic sciences. Therefore,
      it is important to understand the aging process of the different components found
      in ink. The aim of this work was to study the drying process of ballpoint ink,
      characterised by the disappearance of volatile solvents from the ink entry.
      Phenoxyethanol is of particularly high interest as it is found in more than 80%
      of the blue ballpoint pens at different concentrations. Liquid extraction
      followed by splitless gas chromatography/mass spectrometry in the selected ion
      mode was used to measure the quantitative decrease of solvents from ink entries
      made with a blue Parker ballpoint pen. Quantities of ethoxyethoxyethanol,
      dipropylene glycol, phenoxyethanol and phenoxyethoxyethanol were studied in ink
      entries up to 1.5 years old, thus allowing to calculate aging curves for this
      particular pen. The low quantities of solvents (in the microgram range for a 1 cm
      ballpoint entry) were found to decrease quickly after deposition of the ink on
      paper through the competitive processes of evaporation and diffusion. Losses of
      up to 75% of solvents were observed after a few seconds. The amount of
      ethoxyethanol stopped decreasing after about 10 days (quantities reached the
      nanogram range for a 1 cm ballpoint entry), while the aging curves of dipropylene
      glycol, phenoxyethanol and phenoxyethoxyethanol level off considerably after 2
      weeks. It was observed that ethoxyethanol, dipropylene glycol and phenoxyethanol
      can also migrate from one sheet of paper to another if placed close enough (e.g.
      in a book or a stack of papers), therefore contamination from fresh ink strokes
      from other paper sheets has to be taken into account for those solvents. In this
      paper we demonstrate that differentiation between fresh ink (<2 weeks) and older
      inks is possible under laboratory storage conditions. For real cases samples,
      more parameters have to be studied and other possible pathways have to be
      considered.

PMID- 16901669
TI  - Forensic palynology in Canada: an overview with emphasis on archaeology and
      anthropology.
AB  - Palynological analysis is shown from published and unpublished Canadian examples
      to be a useful tool in forensic investigation, although the technique is almost
      unknown and therefore under-utilized by forensic investigators. The techniques of
      pollen and spore identification and interpretation are continually improving,
      indicating that the potential for forensic applications is real. Focus in this
      paper is on an updated interpretation of palynological data that was presented
      during a trial involving a scientific test of oral history as part of a claim for
      aboriginal title to a large area of British Columbia (BC) (Delgamuukw versus the
      Queen). Although the original decision in British Columbia Supreme Court was
      decided in favor of the government defendants, an appeal to the Supreme Court of
      Canada overturned the original decision, and established new principles and
      rights for aboriginal peoples.

PMID- 16901670
TI  - Hair as a source of forensic evidence in murder investigations.
AB  - Obtaining palynological and other botanical evidence from murder victims is
      becoming part of routine mortuary protocol in the United Kingdom. Forensic
      pathologists are often keen to cooperate in the collection of classes of material
      that have, in the past, been considered to be of little importance in criminal
      investigation. Work over the last eight years has demonstrated the great value in
      scrutinising cadavers for the presence of plant material and/or soil stains.
      Macroscopic plant remains and palynomorphs (pollen, spores and other microscopic
      entities) retrieved from skin and hair have allowed the differentiation of murder
      scenes from places of eventual deposition. Furthermore, although the opportunity
      has not yet presented itself, obtaining palynological evidence from the hair of
      suspects is feasible. During an offence, the offender might have had physical
      contact with foliage or the ground. Pollen and spore assemblages picked up by
      hair during that activity might provide forensic evidence for contact. Brief
      details of some aspects of case histories are presented to demonstrate the value
      of sampling cadavers. One case has been through the courts while the other is
      ongoing and, therefore, cannot be identified.

PMID- 16901671
TI  - Quantitative analysis of lovastatin in capsule of Chinese medicine monascus by
      capillary zone electrophoresis with UV-vis detector.
AB  - A capillary zone electrophoresis (CZE) method was developed for the quantitative
      analysis of lovastatin (Lvt) in capsule of monascus-Chinese medicine. Lvt in the
      capsule was separated using an electrolyte system consisting of 16% ethanol (v/v)
      in 60 mM Gly-sodium hydroxide buffer, pH 10.5, 16 kV applied voltage, 238 nm
      detection wavelength with a capillary of 51 cm x 75 microm i.d (43 cm to
      detector). Under the optimized conditions, the linear response of Lvt
      concentration ranges from 4.0 to 240 microg/mL with high correlation coefficient
      (r=0.9998, n=9), the limits of detection (LOD) and quantification (LOQ) for Lvt
      are 0.73 and 2.42 microg/mL, the precision values (expressed as R.S.D.) of intra
      day and inter-day are 1.40-2.12% and 1.47-3.88%, respectively. The recoveries of
      the analyte at three concentration levels are 90.28-100.71%. The developed method
      can be well used for the quantification of Lvt in the drug in commercial
      formulations.

PMID- 16901672
TI  - Degradation of vitamin D3 in a stressed formulation: the identification of esters
      of vitamin D3 formed by a transesterification with triglycerides.
AB  - Four unknown degradants in the LC-UV profile of a stressed experimental tablet
      formulation that contains vitamin D3 have been identified by a combination of Ag+
      cationization electrospray ionization (ESI) LC/MS and atmospheric pressure
      chemical ionization (APCI) LC/MS/MS. The peaks elute in the method chromatography
      in two pairs of two peaks. The first pair of peaks has m/z 511 while the second
      pair has m/z 539. The major, first peak of each set of peaks corresponds to the
      octanoate and decanoate ester of vitamin D3, respectively. These are formed by a
      transesterification with the two major fatty acid components (octanoate and
      decanoate) of the triglycerides present in the formulation. The formation of two
      degradation products with each fatty acid is due to the presence of both vitamin
      D3 (major component) and the isomeric pre-vitamin D3 (minor component) in the
      stressed formulation.

PMID- 16901673
TI  - High performance liquid chromatographic determination of etofibrate and its
      hydrolysis products.
AB  - High performance liquid chromatographic (HPLC) method is presented for the
      determination of etofibrate (EF) and its hydrolysis products. The method was
      based on HPLC separation of EF from its hydrolysis products using cyanopropyl
      column at ambient temperature with mobile phase consisting of acetonitrile-10 mM
      potassium dihydrogen phosphate, pH was adjusted to 4.1 using phosphoric acid
      (50:50, v/v). Quantitation was achieved with UV detection at 221 nm based on peak
      area. The flow rate was 1.5 ml min(-1). The proposed method was used to
      investigate the kinetics of acidic hydrolysis process of EF at different
      temperatures and the apparent pseudo first-order rate constant, half-life and
      activation energy were calculated. The kinetics of alkaline hydrolysis process of
      EF using 0.01 M sodium hydroxide at different temperatures cannot be studied as
      the drug is rapidly hydrolyzed in alkaline medium. The pH-rate profile of
      hydrolysis of EF in Britton-Robinson buffer solutions within the pH range 2-10
      were studied.

PMID- 16901674
TI  - Biotechnological advances in the diagnosis of avian coccidiosis and the analysis
      of genetic variation in Eimeria.
AB  - Coccidiosis is an intestinal disease of chickens caused by various species of
      protozoan parasites within the genus Eimeria. This disease has a major economic
      impact to growers and to the poultry industry world-wide. The diagnosis and
      genetic characterization of the different species of Eimeria are central to the
      prevention, surveillance and control of coccidiosis, particularly now given the
      major problems with wide-spread resistance of Eimeria species against
      anticoccidial drugs (coccidiostats) and the residue problems associated with
      these compounds. While traditional methods have had major limitations in the
      specific diagnosis of coccidiosis, there have been significant advances in the
      development of molecular-diagnostic tools. The present article provides a
      background on coccidiosis, reviews the main molecular methods which have been
      used and describes recent advances in the establishment of polymerase chain
      reaction (PCR)-coupled electrophoretic approaches for the specific diagnosis of
      coccidiosis as well as the genetic characterization of species of Eimeria. These
      biotechnological advances are considered to represent a significant step toward
      the improved prevention and control of this important disease of poultry.

PMID- 16901675
TI  - In vitro protective effect of a Jacquez grapes wine extract on UVB-induced skin
      damage.
AB  - Several studies have shown that UV radiation on the skin results in the formation
      of reactive oxygen species (ROS) that interact with proteins, lipids and DNA,
      thus altering cellular functions. The epidermis is composed mainly of
      keratinocytes, rich in ROS detoxifying enzymes and in low-molecular-mass
      antioxidant molecules. However, the increased generation of ROS can overwhelm the
      natural defences against oxidative stress. Therefore treatment of the skin with
      products containing plant-derived antioxidant ingredients may be a useful
      strategy for the prevention of UV-mediated cutaneous damage. In the present study
      we have investigated the in vitro capability of a Jacquez grapes wine extract
      (containing a significant level of proanthocyanidins, together with lower amounts
      of anthocyanins and hydroxycinnamic acids; JW-E), to protect skin against UVB
      induced oxidative damage by using a three-dimensional tissue culture model of
      human epidermis. The endpoints of our experiments were cell viability, release of
      interleukin-1alpha and prostaglandin E(2) (well-known mediators of cutaneous
      inflammatory processes), accumulation in the epidermis of malondialdehyde/4
      hydroxynonenal and protein carbonyl groups (derived by the oxidative damage
      respectively of lipids and proteins) and tissue redox balance (expressed by the
      levels of reduced glutathione, oxidized glutathione, glutathione peroxidase and
      glutathione reductase). Taken together, our findings demonstrate that the JW-E is
      an efficient botanical mixture able to prevent skin oxidative damage induced by
      UV-B exposure and may thus be a potential promising candidate as a skin
      photoprotective agent.

PMID- 16901676
TI  - Peer-mediated social skills training program for young children with high
      functioning autism.
AB  - One of the most prevailing characteristics of children with autism is their
      deficit in social communication skills. The purpose of this study was to evaluate
      the effectiveness of a peer-mediated social skills training (SST) program
      combined with video feedback, positive reinforcement and token system in
      increasing social communication skills in young children with high-functioning
      autism. Four boys with high-functioning autism, ages 6-7 years, participated in
      the study. The social skills training, lasting 12 weeks, targeted six
      communication skills, selected after parent interviews and behavioral observation
      during a pre-training assessment period. One SST session was conducted each week,
      each session lasted 90min and had six structured activities. The training
      effectiveness was evaluated through direct observation of a structured
      interaction period, using an observational coding system. Improvement was
      observed in three out of four children, although individual differences among
      children were seen for changes in two global scales as well as subscales. These
      results suggest that the social skills training was effective in improving social
      communication skills for some children with high-functioning autism. Clinical and
      research implications and future directions for social skills training as well as
      this study's limitations are discussed.

PMID- 16901677
TI  - The variation of intrinsic spatial resolution across the UFOV of scintillation
      cameras.
AB  - The aim of the present study was to investigate in detail the variation of the
      intrinsic spatial resolution across the useful field of view (UFOV) of gamma
      cameras and to explore whether this variation could lead to observable effects in
      clinical images. Two gamma-cameras were used, without their collimators, to
      acquire 560 (99m)Tc point source images at different points across their UFOVs,
      in order to measure the intrinsic spatial resolution at each point. Possible
      clinical effects of the resolution variation were examined on images of a thyroid
      phantom using a LEHR collimator, acquired at different locations on the UFOV and
      at various distances from the collimator. The gamma-camera intrinsic resolution
      varied significantly across the UFOV, being generally lower at the central region
      and deteriorating at the edges. Pronounced local maxima and minima were found at
      points corresponding to the centers of the photomultiplier tubes (PMTs) and
      halfway in between. Maximum differences of more than 50% were observed between
      the points presenting the best and worst intrinsic resolution. Differences
      between neighboring points reached 17%. The effects of resolution variation were
      clearly observable on the thyroid phantom images. It was concluded that an
      appropriate correction algorithm might be necessary in order to correct for the
      variation of the intrinsic spatial resolution across the UFOV of gamma-cameras.

PMID- 16901678
TI  - Paroxysmal kinesigenic choreoathetosis: from first discovery in 1892 to genetic
      linkage with benign familial infantile convulsions.
AB  - Paroxysmal kinesigenic choreoathetosis (PKC) is presently clearly designated as a
      familial movement disorder with autosomal dominant inheritance. We identified a
      family of PKC, in which 6 out of 23 members were affected, and 4 of the affected
      members had a history of infantile convulsions. Thus, this family was also
      considered as a case of infantile convulsions with paroxysmal choreoathetosis
      (ICCA). Video-EEG monitoring of two affected members suggested that PKC is less
      likely to be a form of reflex epilepsy, despite the existence of a history of
      infantile convulsions. Linkage analysis on eight Japanese families, including
      this family, defined the locus of PKC within the pericentromeric region of
      chromosome 16. ICCA and a form of autosomal dominant benign familial infantile
      convulsions (BFIC) were both mapped to the same or nearby region for PKC on
      chromosome 16. Additionally and quite unexpectedly, the locus of wet/dry ear wax
      (cerumen) was found to be located in the same region. Lastly, it was pointed out
      that the priority of the first discovery of PKC in the world should go to a
      Japanese psychiatrist, Shuzo Kure (1865-1932), who published the first detailed
      and almost complete description of a male patient with PKC in a Japanese medical
      journal in 1892.

PMID- 16901679
TI  - Computerized binary scale of auditory speech hallucinations (cbSASH).
AB  - BACKGROUND: Evidence indicates that the neuropathology of auditory verbal
      hallucinations (AVH) varies according to their phenomenological characteristics.
      Therefore, AVH should be subgrouped accordingly in hallucinations research. As
      evaluation of these characteristics depends entirely on the patient report,
      obtaining measurement of the reliability of these reports is crucial. METHOD: A
      computerized binary scale of auditory speech hallucinations (cbSASH) was
      developed to evaluate the phenomenology of AVH. It includes two subscales
      (inconsistency and malingering) to assess the reliability of the patient report.
      The cbSASH was administered along with MMPI-2, a general psychopathology scale,
      which includes similar validity subscales. Thirty-four psychotic patients with
      history of AVH were enrolled in this study. RESULTS: The scores on the
      inconsistency and malingering subscales of the cbSASH were correlated with the
      scores on the corresponding validity subscales in the MMPI-2. The combination of
      the malingering and inconsistency subscales provided robust measures of the
      reliability and ability of the patients' descriptions of their hallucinations.
      CONCLUSION: The cbSASH provides a reliable and comprehensive evaluation of the
      phenomenology of AVH. Consequently, it is possible to subgroup patients according
      to the characteristics of their hallucinations. This refinement of AVH phenotypes
      could reduce the noise and inconsistency noted in AVH and psychosis research.

PMID- 16901680
TI  - Use of flow cytometry for analysis of phage-mediated killing of Enterobacter
      aerogenes.
AB  - In this study, the use of flow cytometry to analyze phage-mediated killing of
      Enterobacter aerogenes under varying conditions of temperature and nutrient
      availability was assessed. Bacteriophage UZ1, specific for an E. aerogenes
      strain, was applied at a multiplicity of infection (MOI) of 1 and 1000 to a
      Teflon surface, artificially infected with its host at a level of 4.5 log cells.
      After incubation for 20 h, bacteriophages were quantified using the soft agar
      layer method. For the quantification of bacterial cells, plate counting and flow
      cytometric analysis of live/dead stained cells were performed in parallel. At an
      MOI of 1, phage treatment was successful only after incubation under nutrient
      rich conditions at 37 degrees C: E. aerogenes cells were not detected and a
      tenfold increase in phage UZ1 was observed. At a MOI of 1000, no E. aerogenes
      cells could be cultured after incubation at 37 and 4 degrees C. However, flow
      cytometric analysis revealed that lysis did not occur at 4 degrees C but was
      achieved during subsequent plate culture. In conclusion, the use of flow
      cytometry enabled identification of culture-based bias during plate culture. The
      flow cytometric assay used in this study proved to be rapid, as this culture
      independent method does not require lengthy incubation periods post-sampling. The
      bacteriophage-mediated killing of E. aerogenes cells on Teflon surfaces indicated
      that disinfection of E. aerogenes with bacteriophage UZ1 can be successful when
      high MOIs are achieved, while at low multiplicities of infection conditions
      favorable for phage replication are required.

PMID- 16901681
TI  - Positive correlation between in vivo and in vitro assays for the evaluation of
      Pseudomonas virulence.
AB  - Some bacterial phenotypes measured in vitro can be used to access bacterial
      virulence, on the premise that they are positively correlated with data from in
      vivo experiments. We show here that in vitro assessment of bacterial phenotypes,
      such as adherence and cytotoxicity, are positively correlated with data from in
      vivo experiments in Drosophila and can be used to assess bacterial virulence in
      vivo. Manipulation of environmental parameters, such as iron availability,
      induced changes in the phenotypes measured in vitro that correlated with changes
      in vivo virulence of all strains tested. Applying these assays, we demonstrate
      the pathogenic potential of a Pseudomonas fluorescens strain, initially isolated
      as a non-pathogenic milk contaminant. This strain displayed adherence and
      cytotoxicity comparable to those of the Pseudomonas aeruginosa pathogenic strain
      PAK, and colonized the infected flies as rapidly as the PAK strain. These results
      indicate that this "a priori" non-pathogenic bacterium is capable of escaping the
      host immune response, supporting the use of in vitro tests for screening of
      potential pathogens.

PMID- 16901682
TI  - The implication of obesity on total antioxidant capacity in apparently healthy
      men and women: the ATTICA study.
AB  - BACKGROUND AND AIM: We evaluated the association of obesity with serum total
      antioxidant capacity (TAC), in a population-based sample of 3042 adults. METHODS
      AND RESULTS: During 2001-2002 we randomly enrolled 1514 men (18-87 years old) and
      1528 women (18-89 years old), from the Attica area in Greece into the study, and
      the sample was stratified by the age-sex distribution of the region (census
      2001). Among several variables we also measured serum TAC and weight, height,
      waist and hip circumferences. Waist circumference greater than 102 cm for men and
      88 cm for women was considered an indicator of central fat. METHODS AND RESULTS:
      Mean waist circumference was 98+/-13 cm in men and 84+/-22 cm in women (P<0.001),
      while mean hip circumference was 106+/-28 cm in men and 103+/-13 cm in women
      (P<0.001). Central fat prevailed in 53% of men and 45% of women (P<0.001). Male
      participants with central fat exhibited 5% lower TAC concentrations compared to
      leaner individuals (214+/-35 vs. 226+/-33 micromol/L, P=0.04) and female
      participants with central fat exhibited 7% lower TAC concentrations (256+/-38 vs.
      239+/-27 micromol/L, P=0.03). Similarly, obese or overweight male participants
      had 6% lower TAC concentrations compared to normal weight (217+/-33 vs. 234+/-39
      micromol/L, P=0.03) and female obese or overweight participants had 10% lower TAC
      concentrations (226+/-32 vs. 250+/-30 micromol/L, P=0.02) compared to the others.
      CONCLUSIONS: Our results suggest an inverse relationship between body fat,
      central adiposity and antioxidant capacity, irrespective of age and various other
      potential confounders, namely smoking, physical activity, dietary habits, blood
      pressure, glucose levels, and lipid concentrations.

PMID- 16901683
TI  - Differences in the association of PAI-1 activity with the metabolic syndrome
      between African and Caucasian women.
AB  - BACKGROUND AND AIMS: The association between PAI-1(act) and markers of the
      metabolic syndrome is well established in Caucasian populations, but data on
      African subjects is lacking. The aim of this study was to investigate possible
      differences between the association of PAI-1(act) and markers of the metabolic
      syndrome in Caucasian and African women. METHODS AND RESULTS: Cross-sectional
      data were collected from 95 African and 114 Caucasian women in the Potchefstroom
      district of the North West Province, South Africa. Plasma PAI-1(act) was almost
      twice as high in Caucasians compared to Africans (10.2 versus 5.2 U/mL, p<0.001).
      Correlations between markers of the metabolic syndrome and PAI-1(act) were
      remarkably stronger in Caucasians than in Africans. In multivariate regression
      analyses 56% of the variance of PAI-1(act) could be explained by metabolic
      syndrome variables in the Caucasian group compared to 12% in the African women.
      Waist circumference was the strongest independent predictor of PAI-1(act) in both
      groups. CONCLUSION: This study showed lower PAI-1(act) in African than in
      Caucasian women, along with less associations of PAI-1(act) with markers of the
      metabolic syndrome in the African than in the Caucasian women. The role of PAI
      1(act) in the metabolic syndrome may be less prominent in Africans than in
      Caucasians.

PMID- 16901684
TI  - ACE I/D-corrected Z-scores to identify normal and elevated ACE activity in
      sarcoidosis.
AB  - BACKGROUND: The value of elevated serum angiotensin-converting enzyme (ACE)
      activity in the diagnosis and follow-up in sarcoidosis is a matter of ongoing
      debate. This may be at least related to the insertion (I)/deletion (D)
      polymorphism in the ACE gene (ACE I/D). ACE activity is influenced by the ACE I/D
      polymorphism. As a consequence, the use of one reference interval instead of
      three genotype-specific reference intervals for ACE activity may lead to a less
      precise interpretation of ACE activity. METHODS: In order to assess whether
      determination of ACE activity indeed requires the ACE I/D genotype to be taken
      into account, we established ACE I/D-corrected reference intervals in healthy,
      Caucasian volunteers (n=200). In addition, ACE activities in ACE I/D genotyped
      patients suspected of or having sarcoidosis (n=129) were expressed as the Z-score
      related to ACE I/D-corrected reference intervals. RESULTS: Comparison of the Z
      score with ACE activity in which ACE I/D is ignored rendered 8.5%
      misclassification of 'elevated' versus 'normal' ACE or vice versa. CONCLUSIONS:
      Our data demonstrate a convenient way to circumvent the use of three reference
      intervals by introducing a Z-score for ACE activity. It also illustrates the need
      to re-investigating the possible clinical value of serum ACE activity in
      sarcoidosis by considering ACE I/D.

PMID- 16901685
TI  - Detection of Rev peptides with impedance-sensors--comparison of device
      geometries.
AB  - Two different impedance-sensor geometries have been compared for the detection of
      Rev peptides with a molecular weight of 2.4 kDa. Planar, two-dimensional
      interdigitated capacitor (IDC) sensors with electrode separations of 1.1 microm
      as well as three-dimensional nanogap-sensors with an electrode separation of 75
      nm have been used. Both sensors have been operated at a fixed frequency of 980
      MHz. We discuss the specific interaction of the Rev peptide to an immobilized RNA
      anti-Rev aptamer (9.2 kDa) for peptide concentrations in the range of 100 nM-2
      microM. For the IDC sensor, only peptide concentrations above 500 nM gave
      detectable signals. For the nanogap sensor, the binding process was clearly
      visible for all concentrations applied. The higher sensitivity of the nanogap
      compared to the IDC is ascribed to the improved surface-to-volume ratio.

PMID- 16901686
TI  - Marine pharmacology in 2003-2004: anti-tumour and cytotoxic compounds.
AB  - During 2003 and 2004, marine pharmacology research directed towards the discovery
      and development of novel anti-tumour agents was published in 163 peer-reviewed
      articles. The purpose of this review is to present a structured assessment of the
      anti-tumour and cytotoxic properties of 150 marine natural products, many of
      which are novel compounds that belong to diverse structural classes, including
      polyketides, terpenes, steroids and peptides. The organisms yielding these
      bioactive marine compounds include invertebrate animals, algae, fungi and
      bacteria. Anti-tumour pharmacological studies were conducted with 31 structurally
      defined marine natural products in a number of experimental and clinical models
      that further defined their mechanisms of action. Particularly potent in vitro
      cytotoxicity data generated with murine and human tumour cell lines was reported
      for 119 novel marine chemicals with as yet undetermined mechanisms of action.
      Noteworthy is the fact that marine anti-cancer research was sustained by a global
      collaborative effort, involving researchers from Australia, Austria, Canada,
      China, Egypt, France, Germany, Italy, Japan, Mexico, the Netherlands, New
      Zealand, Papua New Guinea, the Philippines, South Africa, South Korea, Spain,
      Switzerland, Taiwan, Thailand and the United States of America (USA). Finally,
      this 2003-2004 overview of the marine pharmacology literature highlights the fact
      that the discovery of novel marine anti-tumour agents continued at the same pace
      as during 1998-2002.

PMID- 16901687
TI  - Impact of pattern of recurrence on clinical outcome of ovarian cancer patients:
      clinical considerations.
AB  - Recurrence of disease represents a clinical challenge in ovarian cancer patients.
      The aim of this study was to analyse the distribution and pattern of recurrence
      and their association with clinical outcome in a large series of ovarian cancer
      patients. This study was conducted on 328 primary untreated ovarian cancer
      patients. For each relapse, information on date of clinical/instrumental
      recurrence, and pattern of disease presentation were retrieved. In stage III-IV
      cases (n = 270), diffuse abdominal carcinomatosis occurred in 62.1% of cases,
      while recurrences presented as a single lesion or multiple nodules occurred in
      9.9% and 26.7% of cases, respectively. Pattern of recurrence as carcinomatosis
      was shown to be associated with unfavourable outcome even when stratified
      according to platinum free interval (PFI) duration. In multivariate analysis,
      pattern of recurrence and PFI duration retained an independent prognostic role
      for post-relapse survival. Duration of PFI and type of recurrence may
      independently influence post-relapse survival in ovarian cancer patients.

PMID- 16901688
TI  - Diffusivity and distribution of vinblastine in three-dimensional tumour tissue:
      experimental and mathematical modelling.
AB  - The distribution of chemotherapeutics in solid tumours is poorly understood and
      the contribution it makes to treatment failure is unknown. Novel approaches are
      required to understand how the three-dimensional organisation of cancer cells in
      solid tumours affects drug availability. Since convective drug transport is
      limited by increased interstitial pressure in poorly vascularised cancers, the
      aim of this study was to measure the diffusive hindrance exerted by solid tumour
      tissue. Multicell layer tumour models comprising DLD1 colon cancer cells were
      characterised and fluxes were determined for [3H]-vinblastine and [14C]-sucrose.
      The mathematical models provided the diffusion coefficients for both compounds
      and predicted higher exposure of cells in the vicinity of vessels. The diffusion
      of vinblastine was three times slower than that of sucrose. Although slow
      diffusion delays vinblastine penetration into the avascular regions of tumours,
      the proliferating cells are generally in the marginal area of tumours. The
      mathematical model that we have developed enabled accurate quantification of drug
      pharmacokinetic behaviour, in particular, the diffusivity of vinblastine within
      solid tissue. This mathematical model may be adapted readily to incorporate the
      influence of factors mediating pharmacokinetic drug resistance.

PMID- 16901689
TI  - The absence of a functional nuclear receptor element A (NREA) in the promoter II
      of the aromatase P450 gene in rabbit granulosa cells.
AB  - Aromatase protein is synthesized in response to gonadotropins that activate
      expression of their target genes via the cAMP second messenger system. The 
      882/+103 bp region of the rabbit ovarian promoter (PII) was ligated to a
      luciferase vector and transfected into granulosa cells to elucidated the
      mechanism by which cAMP stimulates transcription. Deletions and mutational
      experiments indicate that (i) a cAMP-response element-like sequence (CLS) present
      at -208 to -200 bp is the main element required for the activation of the rabbit
      PII by cAMP and that (ii) both nuclear receptor element sites; NREA (-133/-126
      bp) and NREB (-188/-181 bp) do not participate to the cAMP-dependent activity of
      the PII. The replacement of the specific rabbit NREA site by the human NREA site
      increases two-fold the cAMP response and indicates that trans-activating factors
      are present in rabbit granulosa cells. This study shows for the first time an
      efficient aromatase transcription occurs in granulosa cells in absence of a
      consensus NREA site. In addition a comparative study has been performed on the
      sheep aromatase promoter where sites deviate from rabbit. Mutagenesis experiments
      suggest that some of them are involved in the cAMP-induced response of the rabbit
      PII.

PMID- 16901690
TI  - Nutrient changes and biodynamics of epigeic earthworm Perionyx excavatus
      (Perrier) during recycling of some agriculture wastes.
AB  - Potential of an oriental composting earthworm: Perionyx excavatus (Perrier) to
      decompose waste resources generated from agricultural practices (crop residues,
      farm yard manure, and cattle dung) was studied for 150days under laboratory
      conditions. At the end of experiment, all vermibeds showed significant decrease
      in their organic C content ( approximately 21-29%), while increase in total N (
      approximately 91-144%), available P ( approximately 63-105%), and exchangeable K
      ( approximately 45-90%). P. excavatus showed maximum individual live weight
      (662.05mg) after 120days in MIXED (mixed crop residues+cow dung in 1:1)
      substrate. The maximum growth rate (mg worm(-1)day(-1)) was between 3.79+/-0.08
      and 2.35+/-0.16 on different substrates. The mean number of cocoon production was
      between 394.3+/-23.2 and 690.7+/-23.2 for different experimental beddings. MIXED
      bedding showed maximum reproduction rate (0.23+/-0.004 cocoons worm(-1) day(-1)),
      whereas farmyard manure bedding (FYM) showed least value (0.15+/-0.002 cocoons
      worm(-1)day(-1)). During vermicomposting, the total mortality in worms'
      population was recorded between 0% (in MIXED) and 21.7% (in Jowar straw (Sorghum
      vulgare)+millet straw (Pennisenum typhoides)+sheep manure in 1:1:2 ratio (JMS)).
      The waste decomposition and earthworm production was associated strongly with the
      quality of the substrate, especially with their chemical as well as biological
      composition.

PMID- 16901691
TI  - A new, efficient, and simple method for the one-pot synthesis of alpha
      acetoxyphosphonates from aldehydes under solvent-free conditions.
AB  - A simple, efficient, and new method has been developed for the synthesis of alpha
      acetoxyphosphonates from aldehydes through a one-pot reaction of aldehydes with
      diethylphosphite in the presence of acetic anhydride under solvent-free
      conditions using magnesium oxide. This method is easy, rapid, and high yielding
      for the one-pot synthesis of alpha-acetoxyphosphonates from aldehydes.

PMID- 16901692
TI  - Substituted 5-benzyl-2-phenyl-5H-imidazo[4,5-c]pyridines: a new class of
      pestivirus inhibitors.
AB  - A novel class of inhibitors of pestiviruses (5-substituted 2-phenyl-5H
      imidazo[4,5-c]pyridines) is described. Modification of the substituent in
      position 5 resulted in analogues with high activity (EC(50)<100nM) and
      selectivity (SI>1000) against the pestivirus BVDV (bovine viral diarrhea virus).

PMID- 16901693
TI  - Synthesis and structure-activity studies of novel benzocycloheptanone
      oxazolidinone antibacterial agents.
AB  - We describe a novel class of benzocycloheptanone derived oxazolidinone
      antibacterial agents. The synthesis and antibacterial activities with structure
      variation is discussed.

PMID- 16901694
TI  - Synthesis and activity of a folate peptide camptothecin prodrug.
AB  - A folate receptor targeted camptothecin prodrug was synthesized using a
      hydrophilic peptide spacer linked to folate via a releasable disulfide carbonate
      linker. The conjugate was found to possess high affinity for folate receptor
      expressing cells and inhibited cell proliferation in human KB cells with an
      IC(50) of 10nM. Activity of the prodrug was completely blocked by excess folic
      acid, demonstrating receptor-mediated uptake.

PMID- 16901695
TI  - Stereospecificity in hydroxyl radical scavenging activities of four ginsenosides
      produced by heat processing.
AB  - The activity-guided fractionation of sun ginseng (SG, heat processed Panax
      ginseng C. A. Meyer at 120 degrees C) was carried out to identify its main active
      hydroxyl radical (*OH) scavenging components. As a result, the n-BuOH fraction
      mainly consisting of ginsenosides showed the strongest activity. Of several
      ginsenosides of SG, the *OH scavenging activities of relatively high contents of
      20(S)-Rg(3), 20(R)-Rg(3), Rk(1), and Rg(5) were compared. Rg(5) and 20(S)-Rg(3)
      showed strong *OH scavenging IC(50) values of 0.15 and 0.44 mM, respectively, and
      these activities were prominently higher than each of their respective isomers.
      Therefore, stereospecificity exists in the *OH scavenging activities of
      ginsenosides produced by heat processing. Especially, the double bond at carbon
      20(22) or the OH group at carbon-20 geometrically close to OH at carbon-12 is
      thought to increase the *OH scavenging activity of ginsenosides.

PMID- 16901696
TI  - Vialinin B, a novel potent inhibitor of TNF-alpha production, isolated from an
      edible mushroom, Thelephora vialis.
AB  - A novel dibenzofuran compound designated vialinin B was isolated from dry
      fruiting bodies of an edible mushroom, Thelephora vialis, and potently inhibits
      TNF-alpha production in RBL-2H3 cells (IC(50)=0.02nM) and is a promising anti
      allergic agent.

PMID- 16901697
TI  - Breast duct micro-endoscopy.

PMID- 16901698
TI  - Cellular functions of the Spir actin-nucleation factors.
AB  - The initiation of actin polymerization from free monomers requires actin
      nucleation factors. Spir proteins nucleate actin polymerization by a novel
      mechanism that is distinct from actin nucleation by the Arp2/3 complex or by
      formins. In vitro actin polymerization assays and electron microscopic data show
      that Spire nucleates actin polymerization by binding four actin monomers to a
      cluster of four Wiskott-Aldrich syndrome protein-homology domain 2 (WH2) domains
      in the central region of the proteins. Although the exact cell biological
      function and regulation of Spir proteins is still unknown, data from genetic
      studies in Drosophila, cell biological studies and protein interaction
      experiments have provided insight into the biology of these interesting and novel
      actin-nucleation factors and suggest a role in vesicle transport processes and in
      the coordination of cortical microtubule and actin filaments. Phosphorylation by
      mitogen-activated protein kinases and interaction with Rho GTPases have been
      proposed as regulatory mechanisms.

PMID- 16901699
TI  - An evaluation of an early warning clinical marker referral tool.
AB  - OBJECTIVES: The purpose of this study was to evaluate the introduction of a
      clinical marker tool using a pre- and post-test design in a tertiary university
      affiliated hospital. The clinical marker tool was designed to assist in the early
      identification of unstable patients in the general surgical and medical ward
      environment based on abnormal vital signs. METHODS: A pre- and post-test design
      of the clinical marker tool was undertaken over a 3-year period. All unstable
      ward patients who were admitted to the Intensive Care Unit (ICU) from 1 February
      2002 to 31 January 2003 (pre- implementation period) and from 1 February 2003 to
      31 January 2005 (post-implementation period) were included in the study. A
      secondary analysis was performed on annual medical emergency calls made to the
      resuscitation team and mortality from such events from 1 January 2002 to 31
      December 2004. RESULTS: Prior to implementing the clinical marker tool, 63
      (41.2%) unplanned ICU admissions from the ward had clinical markers present for >
      or =6h. Following implementation of the clinical marker tool, 101 (24.5%)
      patients had clinical markers present for > or =6h (p=0.0002). There was no
      difference in ICU or hospital length of stay or hospital mortality for unplanned
      admissions to the ICU following implementation of the clinical marker tool. The
      number of patients found to be still breathing with a pulse on arrival of the
      resuscitation team was significantly increased from 56 (47.9%) patients to 181
      (64.6%) patients post-implementation of the clinical marker tool (p=0.0024).
      Additionally, we found an associated increase in survival of this group of
      patients discharged home from 33 (59%) patients to 136 (75.1%) patients post
      implementation of the clinical marker tool (p=0.0003). CONCLUSIONS: The clinical
      marker tool implemented by an ICU Liaison Team improved the management of
      patients in the ward environment, including proactive admission of patients to
      the ICU. Additionally, implementation of the clinical marker tool was associated
      with a reduction in the number of cardiac arrests and improvement in hospital
      mortality for patients experiencing a medical emergency call. The timeframe of
      instability on the ward prior to the ICU admission may be used as a quality
      indicator to measure ICU Liaison Team performance. Further research is required
      to substantiate these findings.

PMID- 16901700
TI  - The pathophysiology of emphysema: considerations for critical care nursing
      practice.
AB  - Emphysema is caused by exposure to cigarette smoking as well as alpha(1)
      antitrypsin deficiency. It has been estimated to cost the National Health Service
      (NHS) in excess of 800 million pounds per year in related health care costs. The
      challenges for Critical Care nurses are those associated with dynamic
      hyperinflation, Auto-PEEP, malnutrition and the weaning from invasive and non
      invasive mechanical ventilation. In this paper we consider the impact of the
      pathophysiology of emphysema, its effects on other body systems as well as the
      impact acute exacerbations have when patients are admitted to the Intensive Care
      Unit.

PMID- 16901701
TI  - Delusional memories from the intensive care unit--experienced by patients with
      physical trauma.
AB  - During and after intensive care unit (ICU) stays some patients report unreal
      experiences or so called delusional memories, which can be a source of distress.
      The aims of this study were: to describe trauma patients' memories of their stay
      in the ICU, factors that may influence delusional memories, problems experienced
      after discharge from the ICU and the patients' return to work. In this multi
      centre study, 239 trauma patients filled in a self-administered questionnaire
      (ICUM tool) 6-18 months after their ICU stay. Clinical data were obtained from
      patient records. Fifteen percent of the respondents had no memory whatsoever of
      the ICU. Factual memories such as visits by family members were recalled by 83%.
      Delusional memories were reported by 26%, nightmares being the most common. These
      patients' also had more memories of pain, fear and panic. Significant factors
      associated with delusional memories were age <50 year, ICU stay >or=3 days,
      temperature >or=38 degrees C, S-Haemaglobin <or=100g/l, renal failure, surgery,
      ventilator support, sedative drugs, and opioids. A logistic regression analysis
      of all significant factors revealed that age was the best predictor of delusional
      memories. Significantly more patients with delusional memories reported
      unexplained feelings of panic after discharge from the ICU and had still not
      returned to work 1 year after the trauma. In conclusion, patients with delusional
      memories are younger and these memories affect them even after discharge from the
      ICU.

PMID- 16901702
TI  - In-shoe pressure distribution in "unstable" (MBT) shoes and flat-bottomed
      training shoes: a comparative study.
AB  - BACKGROUND: Footwear comfort in many clinical situations is dependent on the
      ability of the 'shoe' to redistribute plantar pressure. Offloading the metatarsal
      heads may be achieved by fitting an insole, but recently a new design of shoe
      with a curved under sole (Masai Barefoot Technology or "MBT shoe") has been
      advocated. The aim of this study was to directly assess the effect of such shoes
      on gait pattern. METHODS: Normal subjects were recruited and asked to walk
      sequentially in (a) flat-soled training shoes and (b) midfoot bearing shoes (MBT
      shoe). Mean and peak pressures in four anatomically defined areas of the foot,
      and the total area of sole contact were measured electronically by an in-shoe
      system (Pedar Ltd., UK). PRINCIPAL RESULTS: Standing in the Masai shoes resulted
      in a 21% lesser peak pressure under the midfoot and an 11% lesser peak pressure
      under the heel in comparison to the figures found when patients wore their
      training shoes. There was a 76% compensatory increase in pressure under the toes.
      In essence there was a significant shift in pressure towards the front of the
      foot.

PMID- 16901703
TI  - A new side to ubiquitin.
AB  - Mono-ubiquitination is a common mechanism of protein regulation, and more than
      ten ubiquitin-interacting domains that recognize the hydrophobic region centered
      on Ile44 of ubiquitin have been characterized. Two recent reports describe the
      crystal structure of the Rab5 guanine-nucleotide-exchange factor Rabex-5 and show
      that it contains two novel ubiquitin-binding domains. One of these is an A20 zinc
      finger that binds to a polar interaction interface of ubiquitin centered on
      Asp58. The discovery of an alternative interaction face of ubiquitin opens new
      avenues for understanding how this small protein regulates protein function.

PMID- 16901704
TI  - Bilateral spontaneous rupture of the quadriceps tendon as an initial presentation
      of alkaptonuria--a case report.
AB  - Unilateral rupture of the quadriceps tendon is not uncommon, but bilateral
      spontaneous quadriceps tendon rupture is a rare occurrence and is usually
      associated with some underlying predisposing condition. We describe a case of a
      previously healthy patient who presents with bilateral spontaneous rupture of
      both quadriceps tendon. Investigations revealed that he had underlying
      alkaptonuria which was previously undiagnosed. Alkaptonuria is a rare inborn
      metabolic disease, which results in the derangement of homogentisic acid
      metabolism. Excessive accumulation of homogentisic acid is known to affect
      multiple organ systems, resulting in tendinopathy and arthropathy in the
      muscoskeletal system.

PMID- 16901706
TI  - TEM-nanoindentation studies of semiconducting structures.
AB  - This paper reviews the application of nanoindentation coupled with transmission
      electron microscopy (TEM) to investigations of the plastic behaviour of
      semiconducting structures and its implication for device design. Instrumented
      nanoindentation has been developed to extract the mechanical behaviour of small
      volumes scaled to those encountered in semiconductor heterostructures. We
      illustrate that TEM is a powerful complementary tool for the study of local
      plasticity induced by nanoindentation. TEM-nanoindentation allows for detailed
      understanding of the plastic deformation in semiconducting structures and opens
      practical routes for improvement of devices. Performances of heterostructures are
      deteriously affected by dislocations that relax the lattice mismatched layers.
      Different ways to obtain compliant substructures are being developed in order to
      concentrate the plastic relaxation underneath the heterostructure. Such
      approaches allow for mechanical design of micro- and opto-electronic devices to
      be considered throughout the fabrication process.

PMID- 16901707
TI  - Imaging of carbon nanotubes with tin-palladium particles using STEM detector in a
      FE-SEM.
AB  - Upgraded FE-SEM with STEM detector permits the observation and imaging of thin
      materials such as carbon nanotubes by transmitted electrons directly in a FE-SEM.
      It is important to know the resolution of transmitted electrons mode compared to
      the classical secondary electrons mode. The resolution was measured with SMART
      macro. This routine permits to quickly determine resolution of a micrograph,
      based on fast Fourier transform analysis. An optimum working distance value was
      found around 6mm for an accelerating voltage equal to 10 keV. In addition to
      this, it was shown that the resolution obtained in bright field and secondary
      electron images at 15 keV had appreciatively the same resolution. Also, it was
      shown that images in dark field mode have a poorer resolution compared with
      bright field transmitted electrons and secondary electrons images.

PMID- 16901708
TI  - Progressive neurodegeneration and motor disabilities induced by chronic
      expression of IL-1beta in the substantia nigra.
AB  - The functional role of the long-lasting inflammation found in the substantia
      nigra (SN) of Parkinson's disease (PD) patients and animal models is unclear.
      Proinflammatory cytokines such as interleukin-1beta (IL-1beta) could be involved
      in mediating neuronal demise. However, it is unknown whether the chronic
      expression of cytokines such as IL-1beta in the SN can alter neuronal vitality.
      The aim of this study was to investigate the effects of the chronic expression of
      IL-1beta in the adult rat SN using a recombinant adenovirus expressing IL-1beta.
      The chronic expression of IL-1beta for 60 days induced dopaminergic cell death in
      the SN and unilateral akinesia starting only at 21 days post-injection.
      Microglial cell activation and inflammatory cell infiltrate were associated with
      dopaminergic cell death and motor disabilities. Astrocytic activation was delayed
      and associated with scar formation. The chronic expression of a single
      proinflammatory cytokine as IL-1beta in the SN elicited most of the
      characteristics of PD, including progressive dopaminergic cell death, akinesia
      and glial activation. Our data suggest that IL-1beta per se is able to mediate
      inflammatory-mediated toxic effects in the SN if its expression is sustained.
      This model will be helpful to identify possible therapeutic targets related to
      inflammation-derived neurodegeneration in the SN.

PMID- 16901709
TI  - Doxorubicin in experimental and clinical heart failure.
AB  - Doxorubicin-induced heart failure is a rare but serious illness due to the well
      known treatment difficulties. Prevention strategies have not demonstrated the
      expected success and unfortunately, this specific type of heart failure does not
      respond to the usual medical therapy as other kinds of heart failure. Therefore,
      surgical procedures may be necessary in some patients. Cardiac transplantation is
      performed in most cases but it requires the cure of the neoplastic disease. This
      usually requires a recurrence-free interval of several years which is associated
      with a high attrition rate in these patients due to their cardiac disease.
      Therefore, other conservative and surgical treatment concepts were developed
      during the last years. This review presents the most common procedures and
      discusses their efficacy as well as their clinical applicability.

PMID- 16901710
TI  - Pulmonary resections for T4 non-small cell lung cancer with support of
      cardiopulmonary bypass.

PMID- 16901711
TI  - Surgery for tumour recurrence in a pneumonectomy space.
AB  - Reoperative surgery through a previous pneumonectomy space focuses on the
      management of postpneumonectomy empyemas and bronchopleural fistulae. There are
      reports of elective tracheal resections done through the pneumonectomy space. We
      report two cases of successful excision of recurrent tumours (leiomyosarcoma and
      carcinoid) performed through the previous pneumonectomy space 2 and 13 years,
      respectively, after the primary surgical resection.

PMID- 16901712
TI  - Pulmonary function following surgical repair of pectus excavatum: a meta
      analysis.
AB  - The purpose of this study was to use a meta-analytical technique to examine the
      efficacy of surgical repair of pectus excavatum on pulmonary function. Studies
      were retrieved via computerized literature searches, cross-referencing from
      original and review articles. Inclusion criteria were as follows: (1) reporting
      quantitative measures of preoperative and postoperative pulmonary function; (2)
      published in the English language; (3) indexed between January 1960 and September
      2005; (4) reporting the duration between which preoperative and postoperative
      assessments were conducted; and (5) describing the pulmonary assessment
      procedures. The titles and abstracts of potentially relevant articles were
      reviewed to determine whether they met the criteria for inclusion. Twelve studies
      representing 313 pectus excavatum patients met the inclusion criteria and were
      used for the meta-analysis. Random-effects modeling yielded a mean weighted
      effect size (ES) for pulmonary function which was statistically nonsignificant
      (ES=0.08, 95% CI=-0.20 to 0.35; P=0.58). The findings of the present study
      indicated that surgical repair of pectus excavatum does not significantly improve
      pulmonary function. These findings, however, may be a result of testing pulmonary
      function under conditions in which pectus excavatum does not manifest itself.

PMID- 16901713
TI  - Transient thoracic duct obstruction in a patient with thoracic outlet syndrome.

PMID- 16901714
TI  - Evaluation of myocardial metabolism with microdialysis during bypass surgery with
      cold blood- or Calafiore cardioplegia.
AB  - BACKGROUND: For the first time, microdialysis was used to investigate in vivo and
      online the myocardial metabolism during and after cardiac surgery in patients
      treated with two different methods of myocardial protection. METHODS: Thirty
      patients underwent standard CABG with one of two different methods of myocardial
      protection. The patients were randomised to receive either cold blood (COLD
      group) or warm modified Calafiore cardioplegia (WARM group). Microdialysis probes
      were implanted into the myocardium of left ventricular apical region of the
      heart. Cardioplegia was given antegrade only. Microdialysis measurements were
      performed at time intervals before, during and 24 h after cardiopulmonary bypass
      and analysed for glucose, lactate, pyruvate and glycerol. RESULTS: Myocardial
      lactate concentrations were significantly higher in the WARM group compared with
      that of the COLD group, while serum lactate was comparable. Glycerol was
      significantly higher at the end of the clamping time in the WARM group. At the
      same time the glucose-lactate ratio as a marker of nutritional disorder had
      significantly lower levels in the WARM group. The cumulative CK-MB release over
      24 h was significantly higher in those hearts protected with warm blood.
      CONCLUSIONS: The oxidative stress measured was significantly higher in patients
      undergoing CABG using modified Calafiore cardioplegia, whereas the cold
      cardioplegia minimised the effects of aortic clamping. The results indicate that
      cold cardioplegia offers superior protection of the heart, in terms of more rapid
      normalisation of myocardial metabolism. In elective myocardial revascularisation,
      intermittent antegrade warm blood cardioplegia is a comparable safe method of
      myocardial protection. However, in patients referring to a long clamping time,
      advantages of cold cardioplegia for myocardial revascularisation may be
      magnified.

PMID- 16901715
TI  - TAM receptor function in the retinal pigment epithelium.
AB  - The TAM receptor tyrosine kinase Mer is expressed by cells of the retinal pigment
      epithelium (RPE), and genetic studies have demonstrated that Mer is essential for
      RPE function. RPE cells that lack Mer exhibit a severely compromised ability to
      phagocytose the distal ends of photoreceptor (PR) outer segments, which leads to
      the complete postnatal degeneration of photoreceptors and to blindness. Although
      in vitro experiments have implicated Gas6 as the critical TAM ligand for this
      process, we find that Gas6 mutant mice have a histologically intact retina with
      no photoreceptor degeneration. We further find that, in addition to Mer, RPE
      cells also express another TAM receptor--Tyro 3--and that both of these receptors
      are instead activated independently by the Gas6-related ligand Protein S. This
      protein is also expressed by RPE cells. Finally, we demonstrate that loss of Mer
      function is accompanied by a substantial down-regulation in Tyro 3 as well. These
      observations indicate that both Mer and Tyro 3 act in mouse RPE cells and suggest
      that their biologically relevant ligand in these cells is Protein S.

PMID- 16901716
TI  - High level production of the Magnaporthe grisea fructose 1,6-bisphosphate
      aldolase enzyme in Escherichia coli using a small volume bench-top fermentor.
AB  - The Class II fructose 1,6-bisphosphate aldolase from the Rice Blast causative
      agent Magnaporthe grisea was subcloned in the Escherichia coli vector pT7-7. The
      enzyme was overexpressed using fed-batch fermentation in a small bench-top
      reactor. A total of 275 g of cells and 1.3 g of highly purified enzyme with a
      specific activity of 70 U/mg were obtained from a 1.5L culture. The purified
      enzyme is a homodimer of 39.6 kDa subunits with a zinc ion at the active site.
      Kinetic characterization indicates that the enzyme has a K(m) of 51 microM, a
      k(cat) of 46 s(-1), and a pH optimum of 7.8 for fructose 1,6-bisphosphate
      cleavage. The fermentation system procedure reported exemplifies the potential of
      using a lab-scale bioreactor for the large scale production of recombinant
      enzymes.

PMID- 16901718
TI  - Effects of dissolved oxygen on survival and immune responses of scallop (Chlamys
      farreri Jones et Preston).
AB  - This experiment investigated the effects of dissolved oxygen (DO) on the survival
      and immune responses of scallop Chlamys farreri. The scallops (initial mean dry
      weight of soft tissue 1.52+/-0.10 g) were cultivated in the seawater with
      different DO levels (8.5, 6.5, 4.5, and 2.5mg l(-1), respectively) for 21 d. Each
      treatment had triplicate groups of 35 animals. During the experimental period,
      the scallops were fed with Spirulina maxima, and water temperature ranged from
      15.2 degrees C to 17.5 degrees C, salinity from 29.5 per thousand to 32.5 per
      thousand and pH from 7.5 to 8.2. Survival, specific growth rate (SGR) and total
      haemocyte count (THC) were examined at the end of the study, and superoxide
      dismutase (SOD), acid phosphatase (ACP) and alkaline phosphatase (ALP), were
      examined at 12 h, 24 h, Day 7, Day 14 and Day 21 after being exposed to the
      graded DO levels. The lower DO levels (2.5 and 4.5mg l(-1))resulted in lower
      survivals of scallops, and the survival (81.7%) at 2.5mg 1(-1)DO was
      significantly lower than those (100.0%) at 8.5 and 6.5mg l(-1) DO. Similarly, the
      SGR and THC of scallop gradually reduced with decreasing DO levels, and reached
      significant levels at 2.5mg l(-1) DO (P<0.05). At higher DO levels (8.5 and 6.5mg
      l(-1)), the SOD activity maintained rather stable during the entire sampling
      period. At lower DO levels (4.5 and 2.5mg l(-1)), however, the SOD activity
      significantly increased at 12 h, and then significantly decreased to the levels
      below the normal. At the two lower DO levels, ACP activities had no significant
      changes before Day 7, and then declined to the levels that were significantly
      lower than the normal. Significantly higher ALP activity was only observed at 12
      h in the treatment of 2.5mg l(-1) DO, but in all other treatments and sampling
      times it fluctuated in a narrow range. In conclusion, less than 4.5mg l(-1) DO
      reduced the survival and depressed the immune responses of C. farreri.

PMID- 16901717
TI  - An improved recombinant mammalian cell expression system for human transforming
      growth factor-beta2 and -beta3 preparations.
AB  - Transforming growth factor-beta2 and -beta3 (TGF-beta2 and -beta3) are important
      members of TGF-beta family which play important roles in the growth, maintenance,
      and repair processes of developing embryos, neonates, and adults. Preparation of
      large quantities of these two cytokines, which is necessary for structural
      studies and other applications, has proven to be extremely difficult. We have
      developed a novel Chinese hamster ovary cell-based expression system for high
      level expression and high recovery of recombinant human TGF-beta2 and -beta3. In
      this system, we used a mammalian expression vector which contains a glutamine
      synthetase coding region for amplification, together with a modified TGF-beta2 or
      -beta3 open reading frame for expression. The leader peptide of TGF-beta2 or 
      beta3 was replaced by that from the V-J2-C region of a mouse immunoglobulin kappa
      chain, and a poly-histidine tag was inserted immediately after the leader
      sequence to facilitate protein purification without changing the mature TGF-beta2
      or -beta3 amino acid sequence. In addition, the extreme N-terminal cysteine
      residue of TGF-beta2 or -beta3 was replaced by a serine residue. The resulting
      expression constructs produced two stable cell clones expressing 10 mg of TGF
      beta2 and 8 mg of TGF-beta3 per liter of spent medium. The purification scheme
      involved the use of two simple chromatographic steps with a typical yield of 5 mg
      of TGF-beta2 and 4 mg of TGF-beta3. This method represents a significant
      improvement over previously published methods and may be applicable to other TGF
      beta superfamily members. We further confirmed that latent TGF-beta2 and -beta3
      can be activated by proteolysis and glycolysis, which have not been reported
      before.

PMID- 16901720
TI  - Specificity deficit in the recollection of emotional memories in schizophrenia.
AB  - The influence of emotion on episodic and autobiographical memory in schizophrenia
      was investigated. Using an experiential approach, the states of awareness
      accompanying recollection of pictures from the IAPS and of associated
      autobiographical memories was recorded. Results show that schizophrenia impairs
      episodic and autobiographical memories in their critical feature: autonoetic
      awareness, i.e., the type of awareness experienced when mentally reliving events
      from one's past. Schizophrenia was also associated with a reduction of specific
      autobiographical memories. The impact of stimulus valence on memory performance
      was moderated by clinical status. Patients with schizophrenia recognized more
      positive than negative pictures, and recalled more positive than negative
      autobiographical memories while controls displayed the opposite pattern. A
      hypothesis in terms of a fundamental executive deficit underlying these
      impairments is proposed.

PMID- 16901719
TI  - Cloning and expression analysis of a HSP70 gene from Pacific abalone (Haliotis
      discus hannai).
AB  - Heat shock protein 70 (HSP70), the primary member of HSPs that are responsive of
      thermal stress, is found in all multicellular organisms and functions mostly as
      molecular chaperon. The inducible HSP70 cDNA cloned from Pacific abalone
      (Haliotis discus hannai) using rapid amplification of cDNA ends (RACE), was
      highly homologous to other HSP70 genes. The full-length cDNA of the Pacific
      abalone HSP70 was 2631bp, consisting of a 5'-terminal untranslated region (UTR)
      of 90bp, a 3'-terminal UTR of 573bp with a canonical polyadenylation signal
      sequence AATAAA and a poly (A) tail, and an open reading frame of 1968bp. The
      HSP70 cDNA encoded a polypeptide of 655 amino acids with an ATPase domain of 382
      amino acids, the substrate peptide binding domain of 161 amino acids and a C
      terminus domain of 112 amino acids. The temporal expression of HSP70 was measured
      by semi-quantitative RT-PCR after heat shock and bacterial challenge. Challenge
      of Pacific abalone with heat shock or the pathogenic bacteria Vibrio anguillarum
      resulted in a dramatic increase in the expression of HSP70 mRNA level in muscle,
      followed by a recovery to normal level after 96h. Unlike the muscle, the levels
      of HSP70 expression in gills reached the top at 12h and maintained a relatively
      high level compared with the control after thermal and bacterial challenge. The
      upregulated mRNA expression of HSP70 in the abalone following heat shock and
      infection response indicates that the HSP70 gene is inducible and involved in
      immune response.

PMID- 16901721
TI  - Trauma-related and neutral false memories in war-induced Posttraumatic Stress
      Disorder.
AB  - Recent models of cognition in Posttraumatic Stress Disorder (PTSD) predict that
      trauma-related, but not neutral, processing should be differentially affected in
      these patients, compared to trauma-exposed controls. This study compared a group
      of 50 patients with PTSD related to the war in Bosnia and a group of 50 controls
      without PTSD but exposed to trauma from the war, using the DRM method to induce
      false memories for war-related and neutral critical lures. While the groups were
      equally susceptible to neutral critical lures, the PTSD group mistakenly recalled
      more war-related lures. Both false and correct recall were related more to
      depression than to self-rated trauma. Implications for accounts of false memories
      in terms of source-monitoring are discussed.

PMID- 16901722
TI  - Frequency organization of the 40-Hz auditory steady-state response in normal
      hearing and in tinnitus.
AB  - We used the 40-Hz auditory steady-state response (SSR) to compare for the first
      time tonotopic frequency representations in the region of primary auditory cortex
      (PAC) between subjects with chronic tinnitus and hearing impairment and normal
      hearing controls. Frequency representations were measured in normal hearing
      (n=17) and tinnitus (n=28) subjects using eight carrier frequencies between 384
      and 6561 Hz, each amplitude modulated (AM) at 40-Hz on trials of 3 min duration
      under passive attention. In normal hearing subjects, frequency gradients were
      observed in the medial-lateral, anterior-posterior, and inferior-superior axes,
      which were consistent with the orientation of Heschl's gyrus and with functional
      organization revealed by fMRI investigations. The frequency representation in the
      right hemisphere was approximately 5 mm anterior and approximately 7 mm lateral
      to that in the left hemisphere, corroborating with MEG measurements hemispheric
      asymmetries reported by cytoarchitectonic studies of the PAC and by MRI
      morphometry. In the left hemisphere, frequency gradients were inflected near 2
      kHz in normal hearing subjects. These SSR frequency gradients were attenuated in
      both hemispheres in tinnitus subjects. Dipole power was also elevated in
      tinnitus, suggesting that more neurons were entrained synchronously by the AM
      envelope. These findings are consistent with animal experiments reporting altered
      tonotopy and changes in the response properties of auditory cortical neurons
      after hearing loss induced by noise exposure. Degraded frequency representations
      in tinnitus may reflect a loss of intracortical inhibition in deafferented
      frequency regions of the PAC after hearing injury.

PMID- 16901723
TI  - Increased local gyrification mapped in Williams syndrome.
AB  - Applying a recently developed method to analyze gyrification with excellent
      spatial resolution across thousands of points across the lateral and medial
      cortical surface, we mapped differences in cortical surface anatomy between
      subjects with Williams syndrome (WS; n=42) and an age-matched sample of healthy
      subjects (n=40). WS subjects showed increased gyrification bilaterally in
      occipital regions and over the cuneus. Differences were more pronounced in the
      left hemisphere than in the right, with additional regions of increased
      gyrification in WS in the left precuneus, posterior and anterior cingulate,
      paracentral and mesial frontal lobe. No cortical area was significantly more
      convoluted in healthy subjects relative to the WS subjects. On the lateral
      surfaces, the direction and pattern of gyrification asymmetries were similar in
      WS subjects and controls; posterior brain regions had greater gyrification in the
      left hemisphere, while anterior brain regions showed greater gyrification in the
      right hemisphere. On the medial surfaces, control subjects and WS individuals
      differed considerably with respect to the degree but also direction of
      gyrification asymmetry. Our findings confirm and extend previous studies
      measuring cortical complexity at the global whole-brain or hemispheric levels.
      The observed gyrification abnormalities in individuals with WS might be related
      to dysfunctions in neuronal circuits and consequently contribute to the distinct
      cognitive and behavioral profile accompanying the disorder.

PMID- 16901724
TI  - Is MRI fulfilling its promise for molecular imaging of cartilage in arthritis?

PMID- 16901725
TI  - Perinuclear localization of biogenic amines (serotonin and histamine) in rat
      immune cells.
AB  - EDAC fixation, which polymerizes biogenic amines, and clorgyline, which blocks
      monoamine oxydase, were used to demonstrate the perinuclear and nuclear
      localization of histamine and serotonin (5-HT) of immune cells in rat peritoneal
      fluid and thymus. For detection, an immunocytochemical method combined with
      confocal microscopy was used. In peritoneal cells (lymphocytes) 5-HT formed spots
      around the nucleus, while histamine was localized diffusely. In thymocytes, 5-HT
      was distributed in patches, while histamine formed a garland around the nuclear
      envelope. Clorgyline enhanced the fluorescence and increased the number of
      fluorescent positive cells only for histamine, and then histamine-positive nuclei
      were also present. The results show that: (1) EDAC fixation demonstrates the
      presence of biogenic amines in immune cells, (2) using this fixation, the
      perinuclear localization of biogenic amines can be demonstrated, (3) the
      localization of the two amines is different and (4) the nuclear localization of
      histamine in thymocytes can be surmised and in mast cells (described previously)
      is proven again. The potential importance of the nuclear and near-nuclear
      localization of biogenic amines is discussed.

PMID- 16901726
TI  - Impaired integrin-dependent function in Wiskott-Aldrich syndrome protein
      deficient murine and human neutrophils.
AB  - Wiskott-Aldrich syndrome (WAS) is a primary immunodeficiency that manifests as
      increased susceptibility to many pathogens. Although the spectrum of infections
      suffered by WAS patients is consistent with defects in neutrophil (PMN) function,
      the consequences of WAS protein (WASp) deficiency on this innate immune cell have
      been unclear. We report that deficiency of WASp in both human and murine PMNs
      resulted in profound defects in clustering of beta2 integrins, leading to
      defective adhesion and transendothelial migration under conditions of physiologic
      shear flow. Wild-type PMNs redistributed clustered beta2 integrins to the uropod
      of the cell during active migration, whereas WASp-deficient cells remain
      unpolarized. The WASp-deficient PMNs also showed reduced integrin-dependent
      activation of degranulation and respiratory burst. PMNs from a WAS patient
      manifested similar defects in integrin clustering and signaling. These results
      suggest that impaired beta2 integrin function in WASp-deficient PMNs may
      contribute substantially to the clinical immunodeficiency suffered by WAS
      patients.

PMID- 16901727
TI  - Human NK cell education by inhibitory receptors for MHC class I.
AB  - Natural killer (NK) cells recognize the absence of self MHC class I as a way to
      discriminate normal cells from cells in distress. In humans, this "missing self"
      recognition is ensured by inhibitory receptors such as KIR, which dampen NK cell
      activation upon interaction with their MHC class I ligands. We show here that NK
      cells lacking inhibitory KIR for self MHC class I molecules are present in human
      peripheral blood. These cells harbor a mature NK cell phenotype but are
      hyporesponsive to various stimuli, including MHC class I-deficient target cells.
      This response is in contrast to NK cells that express a single inhibitory KIR
      specific for self MHC class I, which are functionally competent when exposed to
      the same stimuli. These results show the involvement of KIR-MHC class I
      interactions in the calibration of NK cell effector capacities, suggesting its
      role in the subsequent "missing self" recognition.

PMID- 16901728
TI  - Cytoskeletal regulation couples LFA-1 conformational changes to receptor lateral
      mobility and clustering.
AB  - The alpha(L)beta(2) integrin (leukocyte function-associated antigen-1 [LFA-1]) is
      regulated to engage and maintain T cell adhesion. Conformational changes in the
      receptor are associated with changes in receptor-ligand affinity and are
      necessary for firm adhesion. Less well understood is the relationship between
      receptor conformation and the regulation of its lateral mobility. We have used
      fluorescence photobleaching recovery and single-particle tracking to measure the
      lateral mobility of specific conformations of LFA-1. These measurements show that
      different receptor conformations have distinct diffusion profiles and that these
      profiles vary according to the activation state of the cell. Notably, a high
      affinity conformation of LFA-1 is mobile on resting cells but immobile on phorbol
      12-myristate-13-acetate-activated cells. This activation-induced immobilization
      is prevented by a calpain inhibitor and by an allosteric LFA-1 inhibitor. Our
      results suggest that current models of LFA-1 regulation are incomplete and that
      LFA-1 confinement by cytoskeletal attachment regulates cell adhesion both
      negatively and positively.

PMID- 16901729
TI  - Granzyme B is critical for T cell receptor-induced cell death of type 2 helper T
      cells.
AB  - Although CD95L is required for T cell receptor (TCR)-induced cell death (TCR-ICD)
      in T helper 1 cells, the molecular mechanisms mediating TCR-ICD in Th2 cells are
      unknown. We found that death receptors were not involved in TCR-ICD of Th2 cells
      because blocking their cognate ligands had no effect on apoptosis of activated
      Th2 cells. Furthermore, we showed that caspases were not actively involved in TCR
      ICD of Th2 cells. However, inhibition of granzyme B (GrB) activity abolished TCR
      ICD in Th2 cells but not Th1 cells. Likewise, Th2 cells derived from GrB
      deficient mice were resistant to TCR-ICD, and GrB deficiency or inhibition of GrB
      activity consequently enhanced the production of Th2 cytokines. GrB-deficient
      mice exhibited increased susceptibility to allergen-induced asthma. Thus, GrB
      plays a critical role in the TCR-ICD of Th2 cells.

PMID- 16901730
TI  - Prion proteins as genetic material in fungi.
AB  - Prions are infectious proteins. Several prions have been identified in fungi
      where they behave as non-Mendelian cytoplasmic genetic elements. Most of these
      prions propagate as self-perpetuating amyloid aggregates thus providing an
      example of structural heredity. In yeast, prion propagation requires the Hsp104
      disaggregase presumably to sheer amyloid assemblies and generate more fiber ends.
      Recent work in yeast shows that amyloid structure polymorphism underlies the
      prion strain phenomenon and influences species barriers. Structural models for
      the amyloid form of several fungal prion proteins are now available. All propose
      a cross beta-organization with parallel beta-sheets. Whether or not some of the
      fungal prions might be beneficial to their host is still a debated issue.

PMID- 16901731
TI  - Bacterial adherence to host tissues: a very sticky problem.

PMID- 16901732
TI  - Radiographic techniques for medical-dental research with minipigs.
AB  - Techniques were developed to obtain standardised intra- and extra-oral
      radiographs in minipigs for use in medical-dental research. Twelve male minipigs
      (BR-1 Minipigs) were chosen at random. Two animals each at 3, 5, 7, 9, 12 and 15
      months of age were anaesthetised and subjected to radiographic examinations to
      assess six techniques. Three intra-oral and three extra-oral techniques,
      standardised for humans, were used with variations of the angle of incidence of
      the X-ray beams, focus-film distance and exposure time. Two film positioners were
      developed for the intra-oral techniques. Two examiners then chose the radiographs
      with the least image distortion, greatest clarity and least superimposition of
      images. For each technique, the suitable angle of incidence of the X-ray beams,
      the focus-film distance and exposure time that produced the highest quality
      radiographs were standardised.

PMID- 16901733
TI  - Changes in C-reactive protein and haptoglobin in dogs with lymphatic neoplasia.
AB  - Acute phase proteins (APP) are regarded as a useful diagnostic tool in humans
      with lymphomas, leukaemias and multiple myeloma. C-reactive protein (CRP) and
      haptoglobin concentrations were measured in dogs with malignant multicentric
      (high grade) lymphoma (n=16), acute lymphoblastic leukaemia (ALL) (n=11), chronic
      lymphocytic leukaemia (CLL) (n=7) and multiple myeloma (n=8). Twenty-five healthy
      dogs served as controls. Measurements of the CRP plasma concentration were
      performed using a commercial ELISA and haptoglobin was measured with an assay
      based on its haemoglobin binding capacity. Global group comparisons using Kruskal
      Wallis-test revealed significant group differences for both APPs (P<0.0001).
      Median CRP concentrations were increased in all groups with neoplastic lymphatic
      disorders (lymphoma: 37.2mg/L, ALL: 47.8mg/L, CLL: 35.5mg/L, myeloma: 17.6mg/L)
      compared to controls (1.67mg/L; P<0.001). Compared to the healthy controls
      (median=0.59g/L), haptoglobin was especially increased in dogs with ALL (6.8g/L,
      P<0.0001) followed by dogs with malignant lymphoma (3.8g/L, P<0.0001), CLL
      (3.2g/L, P=0.0008), and multiple myeloma (3.0g/L, P=0.0163). For both APPs, a
      wide range of values was found in all patient groups. The results indicate that
      particularly severe and acute lymphatic neoplasia, such as high grade lymphoma
      and ALL, cause significant acute phase reactions in dogs and must be included in
      the differential diagnoses of increased blood levels of these APPs.

PMID- 16901734
TI  - Controlling coccidiosis in piglets: the importance of the subclinical infection.

PMID- 16901735
TI  - Coagulase gene polymorphisms detected by PCR in Staphylococcus aureus isolated
      from subclinical bovine mastitis in Turkey.
AB  - The genetic relatedness of coagulase (coa) positive Staphylococcus aureus
      isolated from cows with subclinical mastitis in Turkey was investigated by
      polymerase chain reaction (PCR)-based restriction fragment length polymorphism
      (RFLP) analysis. Among 700 milk samples positive in the California Mastitis Test
      (CMT), species specific PCR identified 200 (28.6%) isolates as S. aureus and 161
      (80.5%) of these isolates were positive for the 3' end of the coa gene by PCR.
      Most isolates (n=135, 83.9%) produced a single band on coa PCR, with molecular
      sizes ranging from 500 to 1400bp, whereas a small number of isolates (n=26,
      16.1%) yielded two amplification products. Coa RFLP analysis using AluI and Hin6I
      revealed 23 and 22 band patterns, respectively. The detection of double bands by
      coa PCR, previously reported in human isolates, suggests that milking personnel
      can play a role in the transmission of S. aureus.

PMID- 16901736
TI  - Expression of CD147 and monocarboxylate transporters MCT1, MCT2 and MCT4 in
      porcine small intestine and colon.
AB  - Lactate, formed mainly in the stomach and small intestines, and short-chain fatty
      acids (SCFAs) formed in the colon, are ionised and require transporter proteins
      such as monocarboxylate transporters (MCTs) for absorption. The amounts of MCT1,
      MCT2, MCT4 and CD147, an ancillary protein for MCT1 and MCT4, were measured by
      immunoblotting the small intestine and colon of 40 pigs (Landrace, Yorkshire and
      LandracexYorkshire). MCT1 and MCT4 were found in both small intestine and colon,
      but MCT2 only in the small intestine. In both small intestine and colon,
      Yorkshire pigs had more CD147 than Landrace pigs, while no interbreed differences
      were found in MCT isoforms. Since CD147 is essential for the activity of MCT1 and
      MCT4, the breed difference suggests that MCT activity is higher in Yorkshire than
      in Landrace pigs. The absence of MCT2 in the colon suggests that it is mainly a
      lactate transporter, while MCT1 and MCT4 facilitate the transport of both lactate
      and SCFA.

PMID- 16901737
TI  - Clinico-pathological findings and coagulation disorders in 45 cases of canine
      babesiosis in Spain.
AB  - A retrospective study of clinical cases of babesiosis in dogs examined at the
      Veterinary Teaching Hospital, Rof Codina, from January 2003 to October 2004 is
      presented. The diagnosis was confirmed by direct observation of large piroplasms
      in stained blood smears. Dogs with concurrent diseases were excluded from the
      study. Clinical signs, complete blood count, serum biochemistry and hemostasis
      profiles were obtained. The observed clinical signs were due to hemolytic anemia
      and inflammatory responses but the most relevant clinico-pathological findings
      were related to alterations in hemostasis. All dogs presented with
      thrombocytopenia and 20% had disseminated intravascular coagulation syndrome.
      Anemia of variable severity was observed in most of the dogs.

PMID- 16901738
TI  - High flow-resolution for mobility estimation in 2D-ENMR of proteins using maximum
      entropy method (MEM-ENMR).
AB  - Multidimensional electrophoretic NMR (nD-ENMR) is a potentially powerful tool for
      structural characterization of co-existing proteins and protein conformations. By
      applying a DC electric field pulse, the electrophoretic migration rates of
      different proteins were detected experimentally in a new dimension of
      electrophoretic flow. The electrophoretic mobilities were employed to
      differentiate protein signals. In U-shaped ENMR sample chambers, individual
      protein components in a solution mixture followed a cosinusoidal electrophoretic
      interferogram as a function of its unique electrophoretic migration rate. After
      Fourier transformation in the electrophoretic flow dimension, the protein signals
      were resolved at different resonant frequencies proportional to their
      electrophoretic mobilities. Currently, the mobility resolution of the proteins in
      the electrophoretic flow dimension is limited by severe truncations of the
      electrophoretic interferograms due to the finite electric field strength
      available before the onset of heat-induced convection. In this article, we
      present a successful signal processing method, the Burg's maximum entropy method
      (MEM), to analyze the truncated ENMR signals (MEM-ENMR). Significant enhancement
      in flow resolution was demonstrated using two-dimensional ENMR of two protein
      samples: a lysozyme solution and a solution mixture of bovine serum albumin (BSA)
      and ubiquitin. The electrophoretic mobilities of lysozyme, BSA and ubiquitin were
      measured from the MEM analysis as 7.5x10(-5), 1.9x10(-4) and 8.7x10(-5) cm2 V-1 s
      1, respectively. Results from computer simulations confirmed a complete removal
      of truncation artifacts in the MEM-ENMR spectra with 3- to 6-fold resolution
      enhancement.

PMID- 16901739
TI  - Exploring the molecular basis of the enantioselective binding of penicillin G
      acylase towards a series of 2-aryloxyalkanoic acids: a docking and molecular
      dynamics study.
AB  - In the present paper, molecular modeling studies were undertaken in order to shed
      light on the molecular basis of the observed enantioselectivity of penicillin G
      acylase (PGA), a well known enzyme for its industrial applications, towards 16
      racemic 2-aryloxyalkanoic acids, which have been reported to affect several
      biological systems. With this intention docking calculations and MD simulations
      were performed. Docking results indicated that the (S)-enantiomers establish
      several electrostatic interactions with SerB1, SerB386 and ArgB263 of PGA.
      Conversely, the absence of specific polar interactions between the (R)
      enantiomers and ArgB263 seems to be the main reason for the different binding
      affinities observed between the two enantiomers. Results of molecular dynamics
      simulations demonstrated that polar interactions are responsible for both the
      ligand affinity and PGA enantiospecificity. Modeling calculations provided
      possible explanations for the observed enantioselectivity of the enzyme that
      rationalize available experimental data and could be the basis for future protein
      engineering efforts.

PMID- 16901740
TI  - Post-hatching growth and development of the pectoral and pelvic limbs in the
      black noddy, Anous minutus.
AB  - The black tern (Anous minutus) uses a semi-precocial growth strategy. Terrestrial
      locomotor capacity occurs soon after hatching, but pectoral limb development is
      delayed and flight is not possible until about post-hatching day 50. A growth
      series (hatchlings to fledglings) was used to explore how limb musculoskeletal
      development varied with body mass. In the pelvic limb, bone lengths scaled
      isometrically or with negative allometry. Gastrocnemius muscle mass and the
      failure load and stiffness of the tibiotarsus scaled isometrically. In the
      pectoral limb, pectoralis and supracoracoideus muscle masses increased with
      strong positive allometry that was mirrored by increases in wing bone strength
      and stiffness. Bending strength (sigma(ult)) and modulus (E) remained fairly
      constant throughout development to fledging for all limb bones. The moment of
      inertia (I) scaled with negative allometry for the tibiotarsus and with strong
      positive allometry in the wing bones. Differences in sigma(ult) and E of the
      tibiotarsus between pre-fledged chicks and adults was due, primarily, to
      increases in bone density rather than increases in the moment of inertia of the
      skeletal elements, whereas sigma(ult) of wing bones was a function of increases
      in both bone density and I. Early development of functional pelvic limbs in tree
      nesting birds is relatively unusual, and presumably reflects a familial trait
      that does not appear to compromise breeding success in this species.

PMID- 16901741
TI  - Dietary ascorbic acid may be necessary for enhancing the immune response in
      Siberian sturgeon (Acipenser baerii), a species capable of ascorbic acid
      biosynthesis.
AB  - Siberian sturgeon (Acipenser baerii Brandt) is one of few fish species capable of
      synthesizing ascorbic acid (AA); however, it is unknown whether dietary AA is
      still necessary for this species to generate an optimal non-specific immune
      response, as is found in most teleostean species that do not synthesize AA.
      Sturgeon fed either 0 or 500 mg AA (AA polyphosphate) equivalent kg(-1) diets for
      2 weeks were then either sham or experimentally injected with Aeromonas
      hydrophila lipopolysaccharide (LPS) to mimic infection and therefore instigate a
      non-specific immune response. No significant differences were found in growth and
      survival throughout the duration of the experiment between sham and LPS groups
      and between both diets. Two and eight days after injection, serum lysozyme levels
      were elevated in both LPS and non-LPS groups. Respiratory burst was not affected
      by dietary AA and significantly higher in LPS groups over non-LPS groups;
      however, dietary AA may have enhanced the effects seen in the LPS injected fish
      fed the AA supplemented diet. There were no significant differences in renal l
      gulono-1, 4-lactone oxidase (GLO) activity between dietary and LPS treatments,
      but fish exposed to LPS without dietary AA demonstrated an inter-organ transfer
      of AA from posterior kidney to liver. Our results indicate that dietary AA may be
      conditionally necessary for Siberian sturgeon to achieve optimal immune response,
      particularly in early developmental stages, information imperative to developing
      successful aquaculture programs for sturgeon species.

PMID- 16901742
TI  - Alternative splicing of delta-like 1 homolog (DLK1) in the pig and human.
AB  - Delta-like homolog 1 (DLK1), a paternally imprinted gene with several alternative
      splicing isoforms, is an important regulator of fetal and postnatal development.
      We report the sequence of porcine DLK1 (pDLK1) and examine the expression and
      alternative splicing isoforms in the pig (Sus scrofa) and human. DLK1-A was the
      sole isoform identified in human tissues and has been shown to be present in
      mouse and cattle. Surprisingly, DLK1-A was undetected in various tissues from
      fetal and postnatal pigs. Instead, DLK1-C2 was the most abundant isoform while
      DLK1-B was expressed to a lesser extent. In fractionated adipose tissue, pDLK1
      was most highly expressed in the stromal-vascular cell fraction. In addition,
      total pDLK1 was highly expressed in fetal adipose tissue but dramatically
      decreased postnatally. Our data suggests that expression of DLK1-B and -C2
      isoforms is sufficient for normal pig development. Furthermore, human and pig
      samples showed no alterations in species-specific splicing, but expression levels
      decreased with age, suggesting that regulation of expression, not splicing, is
      the most likely mechanism controlling the biological function of DLK1.

PMID- 16901743
TI  - Influence of femoral head size on impingement, dislocation and stress
      distribution in total hip replacement.
AB  - Dislocation remains a serious complication of total hip replacement. An
      insufficient range of motion can lead to impingement of the prosthetic neck on
      the acetabular cup. Together with the initiation of subluxation and dislocation,
      recurrent impingement can cause material failure in the liner. The objective of
      this study was to generate a validated finite element (FE) model capable of
      predicting the dislocation stability of different femoral head sizes with regard
      to impingement in different implant positions as well as the corresponding stress
      distribution in the liner. In order to cover posterior and anterior dislocation,
      two total hip dislocation associated manoeuvres were simulated using a three
      dimensional nonlinear finite element model. The dislocation stability of two head
      sizes was determined numerically and experimentally. After validation, the FE
      model was used to analyse the dislocation stability of four different head sizes
      in variable implant positions. Range of motion (ROM) until impingement, the
      resisting moment that was developed and ROM until dislocation were evaluated.
      Additionally, stress distribution within the polyethylene liner during
      impingement and subluxation was determined. For both dislocation modes, a cup
      position of 45 degrees lateral abduction and 15 degrees up to 30 degrees
      anteversion resulted in appropriate ROM and dislocation stability. In general,
      larger head diameters revealed an increase in ROM and higher resisting moments.
      Stress analysis showed decreased contact pressures at the egress site of the
      liners with the larger inner diameters during subluxation. The analysis shows
      that an optimal implant position and a larger head diameter can reduce the risk
      of dislocation induced by impingement. The finite element model that was
      developed enables simplification of design variations compared to experimental
      studies since prototyping and assembling are replaced by prompt numerical
      simulation.

PMID- 16901745
TI  - Neuroscientific challenges to free will and responsibility.
AB  - Recent developments in neuroscience raise the worry that understanding how brains
      cause behavior will undermine our views about free will and, consequently, about
      moral responsibility. The potential ethical consequences of such a result are
      sweeping. I provide three reasons to think that these worries seemingly inspired
      by neuroscience are misplaced. First, problems for common-sense notions of
      freedom exist independently of neuroscientific advances. Second, neuroscience is
      not in a position to undermine our intuitive notions. Third, recent empirical
      studies suggest that even if people do misconstrue neuroscientific results as
      relevant to our notion of freedom, our judgments of moral responsibility will
      remain largely unaffected. These considerations suggest that neuroethical
      concerns about challenges to our conception of freedom are misguided.

PMID- 16901744
TI  - Regulation, function and clinical significance of heparanase in cancer metastasis
      and angiogenesis.
AB  - Heparanase is an endoglycosidase which cleaves heparan sulfate (HS) and hence
      participates in degradation and remodeling of the extracellular matrix (ECM).
      Heparanase is preferentially expressed in human tumors and its over-expression in
      tumor cells confers an invasive phenotype in experimental animals. The enzyme
      also releases angiogenic factors from the ECM and thereby induces an angiogenic
      response in vivo. Heparanase upregulation correlates with increased tumor
      vascularity and poor post-operative survival of cancer patients. Heparanase is
      synthesized as a 65 kDa inactive precursor that undergoes proteolytic cleavage,
      yielding 8 and 50 kDa protein subunits that heterodimerize to form an active
      enzyme. Human heparanase is localized primarily within late endosomes and
      lysosomes and occasionally on the cell surface and within the cell nucleus.
      Transcriptional activity of the heparanase promoter is stimulated by
      demethylation, early growth response 1 (EGR1) transcription factor, estrogen,
      inflammatory cytokines and inactivation of p53. N-acetylated glycol-split species
      of heparin as well as siRNA heparanase gene silencing inhibit tumor metastasis
      and angiogenesis in experimental models. These observations and the unexpected
      identification of a single functional heparanase, suggest that the enzyme is a
      promising target for anti-cancer and anti-inflammatory drug development.
      Heparanase exhibits also non-enzymatic activities, independent of its involvement
      in ECM degradation and changes in the extracellular microenvironment. For
      example, cell surface expression of heparanase elicits a firm cell adhesion,
      reflecting an involvement in cell-ECM interaction. Heparanase enhances Akt
      signaling and stimulates PI3K- and p38-dependent endothelial cell migration and
      invasion. It also promotes VEGF expression via the Src pathway. The enzyme may
      thus activate endothelial cells and elicits angiogenic and survival responses.
      Studies with heparanase over-expressing transgenic mice revealed that the enzyme
      functions in normal processes involving cell mobilization, HS turnover, tissue
      vascularization and remodeling. In this review, we summarize the current status
      of heparanase research, emphasizing molecular and cellular aspects of the enzyme,
      including its mode of processing and activation, control of heparanase gene
      expression, enzymatic and non-enzymatic functions, and causal involvement in
      cancer metastasis and angiogenesis. We also discuss clinical aspects and
      strategies for the development of heparanase inhibitors.

PMID- 16901746
TI  - Site-specific mutagenesis of the histidine precursor of diphthamide in the human
      elongation factor-2 gene confers resistance to diphtheria toxin.
AB  - Protein synthesis elongation factor 2 (EF-2) from eukaryotes contains a conserved
      post-translationally modified histidine residue known as diphthamide. Diphthamide
      is a unique site of ADP-ribosylation by diphtheria toxin (DT), which is
      responsible for cell killing. In this report, we describe the construction of DT
      resistant HeLa cell lines by engineering the toxin-resistant form of its specific
      substrate, protein elongation factor-2. Using site-specific mutagenesis of the
      histidine precursor of diphthamide, the histidine residue of codon 715 in human
      EF-2 cDNA was substituted with one of four amino acid residue codons: leucine,
      methionine, asparagine or glutamine. Mutant EF-2s were subcloned into a
      pCMVexSVneo expression vector, transfected into HeLa cells, and DT-resistant cell
      clones were isolated. The protective effect of mutant EF-2s against cell killing
      by DT, after exposing all four mutant strains derived from HeLa cells to
      different concentrations of the toxin (5-20 ng/mL) was demonstrated by: (1) the
      normal morphological appearance of the cells; (2) their unaffected or slightly
      slower growth rates; (3) their undisturbed electrophoretic DNA profiles whose
      integrity was virtually preserved. Mutant cell strains showed also considerable
      levels of resistance to very high concentrations of DT, in that they maintained
      slower but consistent rates of cell growth. It was hence concluded that despite
      its strict conservation and unique modification, the diphthamide histidine
      appears not to be essential to the function of human EF-2 in protein synthesis.
      In addition, DT-resistant HeLa cell clones should prove valuable hosts for
      various DT gene-containing vectors that express the toxin intracellularly.

PMID- 16901747
TI  - IL-10 is up regulated in early and transitional stages in vervet monkeys
      experimentally infected with Trypanosoma brucei rhodesiense.
AB  - IL-10 has been suggested as a possible parameter for human African
      trypanosomiasis stage determination. However, conclusive experimental studies
      have not been carried out to evaluate this, which is a prerequisite before a
      potential test can be validated in humans for diagnostic purposes. We used the
      vervet monkey model of trypanosomiasis to scrutinize IL-10 in blood and
      cerebrospinal fluid (CSF). Five adult males were experimentally infected with T.
      b. rhodesiense. The infected animals became anemic and exhibited weight loss.
      Parasitemia was patent after 3 days and fluctuated around 3.7 x 10(7)
      trypanosomes/ml throughout the experimental period. The total CSF white cell
      counts increased from pre-infection means around 3 cells/micro l to a peak of 30
      cells/micro l, 42 days post-infection (DPI). IL-10 was not detectable (<2 pg/ml)
      in serum prior to infection. IL-10 serum concentrations increased to 273 pg/ml 10
      DPI coinciding with the first peak of parasitemia. Thereafter the levels declined
      to a mean value of 77 pg/ml 34 DPI followed by a significant rise to a second
      peak of 304 pg/ml (p<0.008) 42 DPI. There was no detectable IL-10 in CSF. IL-10
      synthesis is thus stimulated both in the early and transitional stages of
      experimental trypanosomiasis. That IL-10 is produced in early stage disease is an
      interesting finding unlikely to be detected in humans where it is difficult to
      determine the exact time of infection. The IL-10 peak observed on day 42 of
      infection might indicate onset of parasite neuroinvasion coinciding with a peak
      in white blood cell counts in the blood and CSF.

PMID- 16901748
TI  - Phenotypic analysis of adults of Fasciola hepatica, Fasciola gigantica and
      intermediate forms from the endemic region of Gilan, Iran.
AB  - Fascioliasis is an important human and animal disease caused by Fasciola hepatica
      and Fasciola gigantica. In Iran, the distribution of these two species overlaps
      in most areas, including the northern human endemic province of Gilan where both
      fasciolids are simultaneously found in individual cattle and buffaloes. A
      phenotypic study of fasciolid adult flukes from naturally infected bovines from
      Gilan was carried out by means of an exhaustive morphometric analysis using
      traditional microscopic measurements and an allometric model. The Iranian
      fasciolids were compared to F. hepatica and F. gigantica standard populations,
      i.e. from geographical areas where both species do not co-exist (Bolivia and
      Burkina Faso, respectively). Although morphometric values somewhat overlapped,
      there were clear differences in allometric growth. The allometric function was
      adjusted to 25 pairs of variables. Results obtained revealed that Iranian F.
      hepatica-like specimens are larger than the F. hepatica standard and Iranian F.
      gigantica-like specimens are longer and narrower than the F. gigantica standard,
      but with smaller body area. Measurements which permit a specific differentiation
      in allopatric populations (distance between ventral sucker and posterior end of
      the body; ratio between body length and body width) overlap in the specimens from
      Gilan, thus proving the presence of intermediate forms. When compared to the
      standard populations, the different Iranian fasciolid morphs show greater
      differences in F. gigantica-like specimens than in F. hepatica-like specimens.
      This study shows that simple, traditional microscopic measurements may be
      sufficient for the morphometric characterisation of fasciolids, even in areas
      where intermediate forms are present.

PMID- 16901749
TI  - Mobile computing acceptance factors in the healthcare industry: a structural
      equation model.
AB  - OBJECTIVE: This paper presents a revised technology acceptance model to examine
      what determines mobile healthcare systems (MHS) acceptance by healthcare
      professionals. METHOD: Conformation factor analysis was performed to test the
      reliability and validity of the measurement model. The structural equation
      modeling technique was used to evaluate the causal model. RESULTS: The results
      indicated that compatibility, perceived usefulness and perceived ease of use
      significantly affected healthcare professional behavioral intent. MHS self
      efficacy had strong indirect impact on healthcare professional behavioral intent
      through the mediators of perceived usefulness and perceived ease of use. Yet, the
      hypotheses for technical support and training effects on the perceived usefulness
      and perceived ease of use were not supported. CONCLUSION: This paper provides
      initial insights into factors that are likely to be significant antecedents of
      planning and implementing mobile healthcare to enhance professionals' MHS
      acceptance. The proposed model variables explained 70% of the variance in
      behavioral intention to use MHS; further study is needed to explore extra
      significant antecedents of new IT/IS acceptance for mobile healthcare. Such as
      privacy and security issue, system and information quality, limitations of mobile
      devices; the above may be other interesting factors for implementing mobile
      healthcare and could be conducted by qualitative research.

PMID- 16901750
TI  - Healthcare practice ISOlation: articulating systems that drift toward higher
      quality.
AB  - Can higher quality healthcare practices emerge from the development and use of a
      loosely integrated set of intranets? This paper examines that question through a
      series of empirical examples that draw on data from one healthcare organization
      that was part of a multi-year, multi-industry study of intranets. Some of this
      organization's intranets link clinical practice guidelines to healthcare
      delivery, in ways that mimic manufacturing sector efforts to improve product
      quality and reliability. Others act as staging grounds and information
      repositories for coordinating responses to new rulings and changing
      interpretations of how to implement recently enacted healthcare legislation. This
      activity is reminiscent of coordinated responses, among firms and their legal
      counsel, to new legislation in other industries, like telecommunications; and to
      wide-reaching regulatory efforts, like environmental protection. Although the
      technologies have changed and the legislative objectives vary greatly,
      organizational approaches to such improvements are less varied. Ironically, these
      overarching similarities focus attention on the need for continued articulation
      of changes and local differences in information system use, and the ability of
      boundary-spanners to introduce ways of working that bridge these gaps and refine
      healthcare practices that drift toward higher quality.

PMID- 16901751
TI  - Sphingolipid-binding proteins.
AB  - Emerging information on sphingolipid metabolism and signaling is leading to a
      better understanding of cellular processes such as apoptosis, cancer, cell
      survival and aging. In this review, we discuss the involvement of sphingolipids
      in these processes and focus on underlying mechanisms based on
      sphingolipid:protein interactions. Due to the inherent difficulty of studying
      lipids, we discuss techniques that are useful in the elucidation of these
      interactions. We classify sphingolipid-binding proteins into four main classes:
      receptor, effector, enzyme, and transporter. Known structures of sphingolipid
      binding proteins are surveyed, and sphingolipid-binding characteristics are
      described, acknowledging the limitations that there are presently insufficient
      protein:sphingolipid complexes for more definitive conclusions on this topic.
      Finally we summarize relevant literature to better inform the reader about
      sphingolipid:protein interactions.

PMID- 16901752
TI  - Protein engineering of class-A non-specific acid phosphatase (PhoN) of Salmonella
      typhimurium: modulation of the pH-activity profile.
AB  - Engineering of the PhoN enzyme of Salmonella typhimurium due to its superior
      characteristics for bioremediation of heavy metals has been advocated by Macaskie
      and colleagues [Basnakova, G., Stephens, E.R., Thaller, M.C., Rossolini, G.M.,
      Macaskie, L.E., 1998. The use of Escherichia coli bearing a phoN gene for the
      removal of uranium and nickel from aqueous flows. Appl. Microbiol. Biotechnol.
      50, 266-272]. The native enzyme hydrolyzes disparate organophosphates and
      exhibits optimal phosphatase activity at pH 5.5, for instance, with substrate p
      nitrophenyl phosphate. Structurally guided Ile-78 was mutated using site-directed
      mutagenesis to Ala, Asp and His residues, with an aim to shift the optimum pH of
      the PhoN enzyme. Encouragingly, the I78A mutant displays significantly higher (as
      high as 160%) enzymatic efficiency over a broad pH range of 3.0-9.0, compared to
      the wild-type PhoN. The higher catalytic efficiency is due to the increase in
      k(cat), and can be mainly attributed to a deshielding of catalytic His-158 from
      the bulk-solvent. The I78D mutant possesses nearly twice the specific activity at
      the optimum pH of 7.0. The alkaline shift of the pH-activity profile agrees well
      with reasoning based on electrostatics. An increase in K(m), however, lowers the
      catalytic efficiency of the I78D mutant at the optimum pH. The I78H mutant,
      counter-intuitively, also exhibits an alkaline shift in the pH-optimum.
      Nonetheless, the active site scaffold in I78H mutant may not be disturbed, as
      similar steady-state kinetic parameters are observed for both I78H mutant and
      wild-type PhoN at their respective pH optima.

PMID- 16901753
TI  - Promoting physical activity with people in different places--a Dutch perspective.
AB  - This paper describes five recent Dutch studies of the effectiveness of physical
      activity interventions carried out in diverse settings: general practice (GP),
      aged care facilities, and workplaces. The stage-based physical activity
      counselling carried out in the GP setting demonstrated a beneficial effect on the
      determinants of physical activity, but did not show any additional effect on
      physical activity behaviour, compared with standard physical activity advice. In
      contrast, the stage-based intervention through the workplace was effective in
      increasing physical activity, due mostly to an increase in vigorous-intensity
      activities. In the aged care setting, functional-skills training alone or in
      combination with resistance training showed functional improvement only in
      participants with high participation rates. Functional-skills training appeared
      to be more feasible than resistance training in this population of frail elderly.
      The two studies which aimed to promote earlier return-to-work among workers with
      sick leave due to non-specific low back pain also showed promising results. As a
      result, it was recommended that occupational physicians (OP) should refer workers
      with low back pain in the subacute phase of their sick leave to a low intensity
      intervention consisting of short meetings and exercises aimed at changing
      behaviour, and that the OPs contact other health care providers (GPs and
      physiotherapists) about the treatment strategy. Together, the results of these
      five Dutch studies suggest that it is feasible to successfully promote physical
      activity to groups of people in diverse places, with benefits in terms of both
      prevention and management of chronic disease and injury.

PMID- 16901754
TI  - Parasitologists lost?

PMID- 16901755
TI  - Beneficial non-targeted effects of BCG--ethical implications for the coming
      introduction of new TB vaccines.
AB  - Non-targeted effect of BCG: Several recent studies suggest that BCG has
      beneficial non-targeted effects on general child survival in low-income
      countries. Studies of the effect of BCG on morbidity in humans are scarce; some
      found a positive effect of BCG and others show no effect. Non-targeted effects of
      vaccines-possible bias and confounding: The major argument against comparing
      vaccinated and unvaccinated groups is that there is a beneficial social selection
      bias for vaccinated children-the "Healthy vaccinee effect". However, controlling
      for various social and health-related background factors in the survival analyses
      had no effect on the estimates, making this source of bias less likely. A more
      powerful argument that the findings are not due to the healthy vaccinee effect is
      that differential non-targeted effects of other vaccines have been observed;
      diphteria-tetanus-pertussiss vaccination has marked negative effects on child
      survival, whereas measles vaccine has a positive effect in several studies.
      Several studies have shown better survival for children reacting to their BCG
      vaccination with a BCG scar or tuberculin skin test reaction (TST). It could be
      argued that the reacting children were immunologically stronger and therefore
      more likely to survive-the "Healthy reactor effect". However, recent findings
      show that a BCG scar and a TST reaction depend to a large extent on the
      vaccination technique. Hence, the BCG responses may reflect a true vaccine effect
      and not merely the health status of the children. Since HIV-1 has been shown to
      suppress both TST and BCG scar reaction in response to BCG, it is an obvious
      contributor to the healthy reactor effect, but excluding deaths of children with
      HIV-1 infection from analysis did not affect the beneficial effect of having a
      positive TST. Excluding children exposed to tuberculosis (TB) in the household
      did not affect the estimates either. Furthermore, there are strong sex
      differential effects of BCG in both mortality and morbidity data, BCG being more
      beneficial for girls. These observations cannot consistently be explained by the
      healthy vaccinee or healthy reactor effects. Ethical implications: For future TB
      vaccine studies, these findings imply that: These recommendations might be
      considered to delay or to be a too large obstacle for the development and trials
      of new TB vaccines. However, most of the non-targeted beneficial effects of BCG
      have been observed in children below 2 years of age, which is not a long follow
      up time in a TB-vaccine trial. Furthermore, considering the difficulty in setting
      the TB diagnose in children and the lack of reliable TB-protection markers, it
      does not seem unreasonable to argue for monitoring of general morbidity and
      survival in future TB-vaccine trials.

PMID- 16901756
TI  - Seroprevalence of HIV infection among paediatric tuberculosis patients in Agra,
      India: a hospital-based study.
AB  - In this study which was carried over a period of 2 years, from 2003 to 2004, 270
      paediatric patients with active Tuberculosis (TB) disease attending the OPD of
      S.N. Medical College, Agra were screened for Human Immunodeficiency Virus (HIV)
      1/2 antibodies. Of these, 23 were found to be HIV-positive. Seroprevalence of HIV
      infection among paediatric TB patients in Agra is 8.51% (23/270). The HIV
      infection was found to be significantly higher, i.e. 82.61% in male children than
      in female children, i.e. 17.39%. Among the age groups, which were divided into <
      or =1, 2-5, 6-10 and 11-15 years, maximum cases of HIV-positivity, i.e. 65.22%
      was observed in the age group, 2-5 years of age. Among the HIV-positive children
      with TB, 86.75% were of pulmonary and 13.04% were of extra-pulmonary type. Among
      the vaccinated children, 65.22% were found to be HIV-positive, while 34.78% of
      the HIV-positive children were not BCG vaccinated. HIV-positive children are more
      likely to suffer from prolonged fever, weight loss, failure to thrive,
      developmental delay, stunted growth, cough, anorexia, lethargy, lower respiratory
      tract infections (LRTI) and hepatosplenomegaly while HIV negative are more likely
      to suffer from fever, diarrhoea, lymphadenitis, pallor and LRTI. 82.60% (19/23)
      of these TB patients had a history of positive contact with HIV, i.e. one of the
      parents was HIV-infected. The mode of transmission of HIV infection among
      paediatric TB patients was perinatal as revealed during the counselling sessions
      (pre-test and post-test) of both the parents.

PMID- 16901757
TI  - Identification of human T-cell epitopes and highly immunogenic analog peptides on
      the non-typeable Haemophilus influenzae P6 outer membrane protein.
AB  - P6 outer membrane protein is one of the candidates for a vaccine formulation
      against non-typeable Haemophilus influenzae (NTHi) infection. However, otitis
      prone children who have recurrent episodes of acute otitis media due to NTHi fail
      to respond adequately to P6. An innovative approach to vaccination is therefore
      required to augment such children's immune response. To develop an effective
      peptide vaccine, we established P6-specific CD4(+) T-cell lines (TCLs) restricted
      by the human histocompatibility leukocyte antigen (HLA)-DR9 molecule, and
      revealed a human T-cell epitope on P6 and its core peptide sequence (p77-85;
      EYNIALGQR). Furthermore, we found that 3 analog peptides, E77D (the substitution
      of E at position 77 with D), N79G, and R85K, induced high proliferative responses
      as well as marked cytokine production when compared to the T-cell epitope
      peptide. These peptides may be candidates for a peptide vaccine formulation
      effective against NTHi infections, even in otitis-prone children.

PMID- 16901758
TI  - G2 cell cycle arrest and cyclophilin A in lentiviral gene transfer.
AB  - Lentiviral vectors derived from the human immunodeficiency virus-1 (HIV-1) have a
      higher propensity to transduce nondividing cells compared to vectors based on
      oncoretroviruses. We report here that genistein, a previously known protein
      tyrosine kinase (PTK) inhibitor and G2 cell cycle arrest inducer, significantly
      enhanced lentiviral transduction in a dose-dependent manner. Increased
      transduction, as measured by vector expression, was seen in a variety of human
      cell lines, murine primary lymphocytes, and primary human CD34(+) peripheral
      blood progenitor cells as well. Increased vector expression was also associated
      with an increase in vector DNA copy number, as assessed by quantitative PCR.
      Genistein-mediated G2 cell cycle arrest, rather than PTK inhibition, appears to
      be the major factor responsible for increased gene transfer. Genistein also
      increases cyclophilin A (CypA) protein, a cellular protein important for
      efficient HIV-1 infection. While we show that CypA(-/-) Jurkat cells transduce
      poorly with lentiviral vectors, genistein does increase gene transfer in CypA
      deficient cells. CypA and G2 cell cycle arrest appear to be two independent
      factors important for efficient lentiviral gene transfer. The role of genistein
      and other G2-arresting agents may be useful for improving the efficiency of
      lentiviral gene therapy.

PMID- 16901759
TI  - Metabolites from algae with economical impact.
AB  - In order to survive in a highly competitive environment, freshwater or marine
      algae have to develop defense strategies that result in a tremendous diversity of
      compounds from different metabolic pathways. Recent trends in drug research from
      natural sources have shown that algae are promising organisms to furnish novel
      biochemically active compounds. The current review describes the main substances
      biosynthesized by algae with potential economic impact in food science,
      pharmaceutical industry and public health. Emphasis is given to fatty acids,
      steroids, carotenoids, polysaccharides, lectins, mycosporine-like amino acids,
      halogenated compounds, polyketides and toxins.

PMID- 16901761
TI  - Feature-guided clustering of multi-dimensional flow cytometry datasets.
AB  - BACKGROUND: Flow cytometry produces large multi-dimensional datasets of the
      physical and molecular characteristics of individual cells. The objective of this
      study was to simplify the cytometry datasets by arranging or clustering "objects"
      (cells) into a smaller number of relatively homogeneous groups (clusters) on the
      basis of interobject similarities and dissimilarities. RESULTS: The algorithm was
      designed to be driven by histogram features; that is, the relevant single
      parameter histogram features were used to guide multidimensional k-means
      clustering without an a priori estimate of cluster number. To test this approach,
      we simulated cell-derived datasets using protein-coated microspheres (artificial
      "cells"). The microspheres were constructed to provide 119 populations in 40
      samples. The feature-guided (FG) approach accurately identified 100% of the
      predetermined cluster combinations. In contrast, an approach based on the
      partition index (PI) cluster validity measure accurately identified 83.2% of the
      clusters. Direct comparisons of the two methods indicated that the FG method was
      significantly more accurate than PI in identifying both the number of clusters
      and the number of objects within the clusters (p<.0001). CONCLUSION: We conclude
      that parameter feature analysis can be used to effectively guide k-means
      clustering of flow cytometry datasets.

PMID- 16901760
TI  - Automated identification of adverse events related to central venous catheters.
AB  - Methods for surveillance of adverse events (AEs) in clinical settings are limited
      by cost, technology, and appropriate data availability. In this study, two
      methods for semi-automated review of text records within the Veterans
      Administration database are utilized to identify AEs related to the placement of
      central venous catheters (CVCs): a Natural Language Processing program and a
      phrase-matching algorithm. A sample of manually reviewed records were then
      compared to the results of both methods to assess sensitivity and specificity.
      The phrase-matching algorithm was found to be a sensitive but relatively non
      specific method, whereas a natural language processing system was significantly
      more specific but less sensitive. Positive predictive values for each method
      estimated the CVC-associated AE rate at this institution to be 6.4 and 6.2%,
      respectively. Using both methods together results in acceptable sensitivity and
      specificity (72.0 and 80.1%, respectively). All methods including manual chart
      review are limited by incomplete or inaccurate clinician documentation. A
      secondary finding was related to the completeness of administrative data (ICD-9
      and CPT codes) used to identify intensive care unit patients in whom a CVC was
      placed. Administrative data identified less than 11% of patients who had a CVC
      placed. This suggests that other methods, including automated methods such as
      phrase matching, may be more sensitive than administrative data in identifying
      patients with devices. Considerable potential exists for the use of such methods
      for the identification of patients at risk, AE surveillance, and prevention of
      AEs through decision support technologies.

PMID- 16901762
TI  - Defensive and pathological functions of the gastrointestinal NK3 receptor.
AB  - In general, normal gut functions are unaffected by selective NK(3) receptor
      antagonists such as talnetant (SB-223412), osanetant (SR 142901) or SB-235375.
      However, NK(3) receptors may mediate certain defensive or pathological intestinal
      processes. The precise mechanisms, by which this role is achieved, are not fully
      understood. In summary, intense stimulation of the intrinsic primary afferent
      neurones (IPANs) of the enteric nervous system is thought to release tachykinins
      from these neurones, to induce slow excitation (slow EPSPs) of connecting IPANs.
      This is hypothesised to cause hypersensitivity and disrupt intestinal motility,
      at least partly explaining why NK(3) receptor antagonism can reduce the level of
      disruption caused by supramaximal distension pressures in vitro. Tachykinin
      release from IPANs may also increase C-fibre sensitivity, directly or indirectly.
      Thus, NK(3) receptor antagonists can inhibit nociception associated with
      intestinal distension, in normal animals or after pre-sensitisation by restraint
      stress. Importantly, such inhibition has been found with SB-235375, a
      peripherally restricted antagonist. SB-235375 can also reduce a visceromotor
      response to brief colorectal distension without affecting similar responses to
      skin pinch, providing additional evidence for intestinal-specific activity. NK(3)
      receptor biology is, therefore, revealing a novel pathway by which disruptions in
      intestinal motility and nociception can be induced.

PMID- 16901764
TI  - Oncogenic and metastatic properties of preprotachykinin-I and neurokinin-1 genes.
AB  - Breast cancer (BC) remains the cancer with highest mortality among women in the
      United States. Entry of BC cells (BCCs) in bone marrow (BM) leads to poor
      prognosis. This review discusses studies showing interactions between BCCs and BM
      stroma, consequently providing BCCs with advantages of survival within BM. Myc
      transcription factor is investigated as a link between the transforming
      properties of peptides derived from the preprotachykinin-I gene (PPT-I) and
      Neurokinin-1 (NK1) receptor. A co-culture method previously described to model
      early integration of BCC in BM is used to study timeline changes of PPT-I and TGF
      beta using northern analyses and a bioassay, respectively. The results show
      changes of both genes in BCCs and BM stroma. Relevance of these changes to
      homeostasis in BM is discussed. Myc has been shown to link the expressions of TGF
      beta1 and PPT-I in BCCs. We now show a role for Myc in the expression of NK1. PPT
      I and the chemokine SDF-1alpha induce the expression of each other through an
      autocrine mechanism. Since a role for Myc in SDF-1alpha-PPT-I axis has not been
      studied, we speculate on this finding, based on the cell-homing property of SDF
      1alpha. Since Myc could be oncogenic, it might be involved in the transforming
      properties of PPT-I and NK1 while SDF-1alpha could be involved in cell-homing of
      BCCs through the regulation of PPT-I. The findings are discussed in the context
      of other related reports.

PMID- 16901763
TI  - Increased vascular contractility in isolated vessels from cigarette smoking rats
      is mediated by basal endothelin release.
AB  - The effect of chronic cigarette smoking on endothelin modulation of vascular
      contraction, and CYP enzyme levels was studied in 20 male Sprague-Dawley rats.
      The animals were divided equally into smoking and non-smoking groups. The smoking
      group was exposed to 6 research cigarettes per rat per day 5 days a week for 16
      weeks. The control group was sham smoked. Functional contractile studies were
      performed in aortas and carotid arteries to determine the regulation of vascular
      tone by basal release of endothelin. Liver samples were analyzed for CYP1A1 and
      CYP1A2 gene expression by RT-PCR. Plasma samples were assessed for endothelin-1
      (ET-1) level by enzyme immuno assay (EIA). Treatment of aortas and carotid
      arteries with bosentan, the dual endothelin receptor antagonist, caused a
      significant reduction in constrictor responses of smoking rats, indicating,
      increase greater regulation of tone by endothelin in smoker rats compared to
      controls. There was a greater expression of the cytochrome P450-liver enzymes
      (CYP1A1 and CYP1A2) in smoker rats. Body weight gain was also significantly
      decreased in smoker rats. We conclude that increased endothelin release in smoker
      rats significantly contributes to increased arterial tone and so contribute to
      the cardiovascular pathophysiology associated with cigarette smoking, such as
      increased vascular muscularization, increased contraction, decreased dilation and
      possibly vasospasm.

PMID- 16901765
TI  - A lean man with nonalcoholic fatty liver disease.

PMID- 16901766
TI  - Familial aggregation of insulin resistance in first-degree relatives of patients
      with nonalcoholic fatty liver disease.
AB  - BACKGROUND & AIMS: An association between nonalcoholic fatty liver disease
      (NAFLD) and the insulin resistance (IR) syndrome exists. Familial clustering of
      IR may support a genetic predisposition to NAFLD or cryptogenic cirrhosis (CC).
      METHODS: Patients with NAFLD (n = 20) and healthy controls (n = 20) matched for
      age, sex, and body mass index with at least 4 living relatives and 2 generations
      of lineage participated in a familial aggregation study. A medical history was
      obtained from each subject and confirmed with first-degree family members.
      RESULTS: NAFLD patients were more likely to have cirrhosis (odds ratio [OR] =
      12.0), cardiac disease (OR, 3.0), hyperlipidemia (OR, 12.1), diabetes mellitus
      (DM) (OR, 9.1), renal stones (OR, 4.1), and arthritis (OR, 6.1). IR (P = .042)
      (the primary dependent variable) and DM (P = .013) were noted in their first
      degree relatives. A trend for familial clustering of NAFLD or CC (P = .059) with
      a maternal linkage for disease expression also may exist. Cholelithiasis (P =
      .047), presumed NAFLD and/or CC (P = .049), and a trend toward IR (P = .07) were
      noted in the mothers, but not the fathers, of patients with NAFLD. An increased
      risk of DM (OR, 4.2; 95% confidence interval, 1.26-18.7; P = .013), IR (OR, 2.86;
      95% confidence interval, 1.02-9.38; P = .042), and smoking (OR, 3.41; 95%
      confidence interval, 1.43-9.07; P = .003) was observed in first-degree relatives
      of NAFLD patients. No significant survival difference was observed between family
      cohorts. CONCLUSIONS: Familial clustering and a potential maternal linkage for IR
      support a genetic predisposition for NAFLD. Alternatively, the presence of
      suppressor genes modifying the expression of IR in paternal lineage warrants
      further investigation.

PMID- 16901767
TI  - Step-up versus top-down: application of new biological agents in pediatric
      inflammatory bowel disease.

PMID- 16901768
TI  - The impact of newer treatment modalities on survival in patients with
      hepatocellular carcinoma.
AB  - BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is one of the most common
      cancers worldwide. However, although the therapeutic approaches for HCC have
      progressed rapidly, it remains unknown whether the current management of patients
      with HCC has reduced its mortality. We analyzed changes of survival rate in
      patients with HCC over a 20-year period. METHODS: Between 1982 and 2001, 463
      patients were diagnosed with HCC at our hospital. Subjects were enrolled in the
      current cohort according to the following inclusion criteria: HCC lesion
      measuring less than 3 cm in diameter, no evidence of extrahepatic metastasis, and
      no evidence of main portal vein infiltration/thrombosis. A total of 257 patients
      with HCC were recruited for this study, and categorized into 5-year intervals.
      RESULTS: The survival rates improved significantly during the study period. When
      the patients were stratified according to Child-Pugh score, only patients with
      Child's B showed improved survival rates. Furthermore, patients with surgical
      resection or transarterial chemoembolization during the latter period had a
      better prognosis than those during the early period. CONCLUSIONS: Our findings
      suggest that the development of therapeutic interventions for HCC have led to
      improvements in the prognosis for HCC patients.

PMID- 16901769
TI  - Incidence of presentation of common functional gastrointestinal disorders in
      children from birth to 5 years: a cohort study.
AB  - BACKGROUND & AIMS: Gastroesophageal reflux disease (GERD), abdominal pain of
      unknown origin, and constipation are thought to be causes for frequent medical
      visits during childhood. The aim of this study was to estimate the incidences,
      repeat presentation, clinical symptoms, and sociodemographic risk factors in
      children who medically presented for GERD, abdominal pain of unknown origin, and
      constipation from birth to 5 years. METHODS: This was a population-based,
      retrospective birth cohort study of all children born to mothers residing in
      Rochester, Minnesota who remained in the area until at least age 5 (n = 5718).
      The medical records of all individuals were searched for relevant diagnostic
      billing codes for GERD, abdominal pain of unknown origin, and constipation,
      without another underlying diagnosis, and manually reviewed. Parental
      sociodemographic factors collected from birth certificate records on patients and
      matched controls were compared. RESULTS: The incidence for childhood (age, <5 y)
      presentation of GERD, abdominal pain of unknown origin, and constipation was
      .9/1000 person-years, 4.5/1000 person-years, and 6.8/1000 person-years,
      respectively; there were no significant differences between boys and girls. Three
      or more medical visits by age 5 occurred in 11%, 19%, and 24% of children who
      were seen for abdominal pain of unknown origin, constipation, and GERD,
      respectively. Single parentage, maternal age (<18 y), and maternal education
      (<high school) were not associated with abdominal pain or constipation
      presentation. CONCLUSIONS: The incidences of presentation for GERD, abdominal
      pain of unknown origin, and constipation are among the highest for pediatric
      disorders, and a cause for repeated medical consultations.

PMID- 16901770
TI  - Assessment of fibrosis progression in untreated irish women with chronic
      hepatitis C contracted from immunoglobulin anti-D.
AB  - BACKGROUND & AIMS: In 1996 we initiated a retrospective-prospective study in 184
      untreated women infected in 1977 with chronic hepatitis C virus (HCV). To provide
      insight into the natural history of HCV, we determined liver fibrosis outcomes
      and any predictors of such. METHODS: Baseline 1994 biopsy specimens (size, >or=15
      mm; portal areas, >or=5) and sequential biopsy specimens were assessed by Ishak
      score for grade change (increase or decrease of >or=2 points) and stage
      progression or regression (increase or reduction of >or=1 point), the latter
      correlated with digital quantification of fibrosis percentage. RESULTS: No
      baseline biopsy specimens had cirrhosis, therefore all could potentially
      progress. Grade and stage scores decreased or increased significantly in 28% and
      18% and 24% and 27% of patients, respectively. There was a positive correlation
      between baseline and sequential grade/stage scores (r = .39, P < .001), and
      between semiquantitative Ishak scores and fibrosis percentage (Spearman rho =
      .85; P < .01). Baseline alanine transaminase values (mean, 49 U/L; range, 23-363
      U/L) correlated positively with changes in grade (r = .41, P < .01) and stage (r
      = .39, P < .01), and regression analyses indicated that baseline alanine
      transaminase value was a good predictor of such changes. Confounding variables
      (alcohol, smoking, and herbal and paracetamol [acetaminophen] use) did not
      correlate with histologic outcomes. CONCLUSIONS: In a follow-up study, 49% of
      patients showed no change in fibrosis, 24% showed regression, and only 27% showed
      progression, including 4 patients (2.1%) who developed stage 6 cirrhosis.
      Unidirectional sequential grade/stage concordance attested to biopsy sample
      reliability. Given the current age of these women in their fifth decade, some
      still may have a risk for more advanced liver disease, but for most of these
      patients it appears unlikely.

PMID- 16901771
TI  - Maintenance of eupnea of in situ and in vivo rats following riluzole: a blocker
      of persistent sodium channels.
AB  - We have proposed a "switching" concept for the neurogenesis of breathing in which
      rhythm generation by a pontomedullary neuronal circuit for eupnea may be switched
      to a medullary pacemaker system for gasping. This switch involves activation of
      conductances through persistent sodium channels. Based upon this proposal, eupnea
      should continue following a blockade of persistent sodium channels. In situ
      preparations of the decerebrate, juvenile rat were studied in normocapnia,
      hypocapnia and hypercapnia. Regardless of the level of CO(2) drive, riluzole (1
      10 microM), a blocker of persistent sodium channels, caused increases in the
      frequency and reductions in peak integrated phrenic height. Even 20 microM of
      riluzole, a concentration four-fold higher than that which eliminates gasping,
      did not cause a cessation of phrenic discharge. In conscious, rats breathing
      continued unabated following intravenous administrations of 3-9 mgkg(-1) of
      riluzole. These administrations did cause sedation. We conclude that conductance
      through persistent sodium channels plays little role in the neurogenesis of
      eupnea.

PMID- 16901772
TI  - Bone tissue compositional differences in women with and without osteoporotic
      fracture.
AB  - It is generally accepted that the hallmark of osteoporosis is a reduction in bone
      mass. There is significant overlap, however, in bone mineral density between
      osteoporotic and normal individuals. This study examined the chemical composition
      of bone tissue obtained from women who had sustained a fracture and women without
      fracture to determine if there are differences between the two groups. Nineteen
      fractured and eleven non-fractured proximal femurs were obtained, matched for age
      and bone volume fraction obtained from micro-computed tomography. Trabecular bone
      specimens were examined by Raman spectroscopy to determine measures of chemical
      composition. A subset of the specimens was utilized to compare locations at the
      fracture and regions at least 2 mm away from apparent tissue damage using Raman
      spectroscopy. In addition, fifteen iliac crest biopsies each were obtained from
      women who had sustained a fracture and from normal controls. Raman spectroscopy
      was used to determine measures of chemical composition of trabecular and cortical
      bone. The results demonstrated that femoral bone tissue in the region of visible
      damage had a trend towards differences compared to regions at least 2 mm from
      visible damage. Femoral trabecular bone in fractured women had a higher
      carbonate/amide I area ratio than in unfractured women. Iliac crest biopsies
      revealed a higher carbonate/phosphate ratio in cortical bone from women who had
      sustained a fracture. Results suggest that the chemical composition of bone
      tissue may be an additional risk factor for osteoporotic fracture.

PMID- 16901773
TI  - Nitrogen removal in the bioreactor landfill system with intermittent aeration at
      the top of landfilled waste.
AB  - High ammonia concentration of recycled landfill leachate makes it very difficult
      to treat. In this work, a vertical aerobic/anoxic/anaerobic lab-scale bioreactor
      landfill system, which was constructed by intermittent aeration at the top of
      landfilled waste, as a bioreactor for in situ nitrogen removal was investigated
      during waste stabilization. Intermittent aeration at the top of landfilled waste
      might stimulate the growth of nitrifying bacteria and denitrifying bacteria in
      the top and middle layers of waste. The nitrifying bacteria population for the
      landfill bioreactor with intermittent aeration system reached between 10(6) and
      10(8) cells/dry g waste, although it decreased 2 orders of magnitude on day 30,
      due to the inhibitory effect of the acid environment and high organic matter in
      the landfilled waste. The denitrifying bacteria population increased by between 4
      and 13 orders of magnitude compared with conventional anaerobic landfilled waste
      layers. Leachate NO(3)(-)-N concentration was very low in both two experimental
      landfill reactors. After 105 days operation, leachate NH(4)(+)-N and TN
      concentrations for the landfill reactor with intermittent aeration system dropped
      to 186 and 289 mg/l, respectively, while they were still kept above 1000 mg/l for
      the landfill reactor without intermittent aerobic system. In addition, there is
      an increase in the rate of waste stabilization as well as an increase of 12% in
      the total waste settlement for the landfill reactor with intermittent aeration
      system.

PMID- 16901774
TI  - Rough sheets and smooth tubules.
AB  - The endoplasmic reticulum (ER) has distinct morphological domains composed of
      sheets and tubules, which differ in their characteristic membrane curvature. Key
      proteins may drive the formation of these structural morphologies, which in turn
      could generate the rough and smooth functional domains of the ER.

PMID- 16901775
TI  - Boning up on ephrin signaling.
AB  - The activities of osteoclasts, which degrade bone, and osteoblasts, which form
      bone, are coordinated to maintain bone homeostasis. Zhao et al. (2006) now
      demonstrate bidirectional signaling between these two cell populations via the
      transmembrane ligand ephrinB2 expressed by osteoclasts and its receptor EphB4
      expressed by osteoblasts. Such bidirectional signaling limits osteoclast activity
      while stimulating osteoblast differentiation.

PMID- 16901776
TI  - ErbB2 makes beta 4 integrin an accomplice in tumorigenesis.
AB  - Integrins modulate signaling by growth factor receptors, but their role during
      tumorigenesis is not clear. Guo et al. (2006) now demonstrate that alpha 6 beta 4
      integrin cooperates with ErbB2 in the formation of mammary tumors and discover
      distinct pathways that regulate cellular proliferation and adhesion downstream of
      the ErbB2-integrin complex.

PMID- 16901777
TI  - The singular history of a canine transmissible tumor.
AB  - In this issue of Cell, Murgia et al. (2006) confirm that the infectious agent of
      canine transmissible venereal tumor is the cancer cell itself and that the tumor
      is clonal in origin. Their findings have implications for understanding the
      relationship between genome instability and transmissible cancer and for
      conservation biology, canine genomics, and companion animal medicine.

PMID- 16901778
TI  - Gap peptides: A new way to control embryonic patterning?
AB  - Gap genes encode transcription factors involved in the patterning of the head
      tail axis of insect embryos. In this issue of Cell, Savard et al. (2006) identify
      a beetle gap gene, mille-pattes, that encodes an unusual polycistronic transcript
      predicted to produce four conserved peptides. These results have interesting
      implications for the control of embryonic patterning in insects.

PMID- 16901779
TI  - A kinase gets caspases into shape.
AB  - Two new papers (Kuranaga et al., 2006; Oshima et al., 2006) describe a previously
      uncharacterized Drosophila kinase (DmIKK epsilon) that regulates the abundance of
      DIAP1, a protein best known for its ability to inhibit apoptosis. However, DmIKK
      epsilon-mediated degradation of DIAP1 does not regulate apoptosis as might be
      predicted but instead regulates actin dynamics, cell morphology, and the
      differentiation of sensory organ precursor cells.

PMID- 16901780
TI  - Molecular interactions between bacterial symbionts and their hosts.
AB  - Symbiotic bacteria are important in animal hosts, but have been largely
      overlooked as they have proved difficult to culture in the laboratory. Approaches
      such as comparative genomics and real-time PCR have provided insights into the
      molecular mechanisms that underpin symbiont-host interactions. Studies on the
      heritable symbionts of insects have yielded valuable information about how
      bacteria infect host cells, avoid immune responses, and manipulate host
      physiology. Furthermore, some symbionts use many of the same mechanisms as
      pathogens to infect hosts and evade immune responses. Here we discuss what is
      currently known about the interactions between bacterial symbionts and their
      hosts.

PMID- 16901781
TI  - Different plant hormones regulate similar processes through largely
      nonoverlapping transcriptional responses.
AB  - Small-molecule hormones govern every aspect of the biology of plants. Many
      processes, such as growth, are regulated in similar ways by multiple hormones,
      and recent studies have revealed extensive crosstalk among different hormonal
      signaling pathways. These results have led to the proposal that a common set of
      signaling components may integrate inputs from multiple hormones to regulate
      growth. In this study, we tested this proposal by asking whether different
      hormones converge on a common set of transcriptional targets in Arabidopsis
      seedlings. Using publicly available microarray data, we analyzed the
      transcriptional effects of seven hormones, including abscisic acid, gibberellin,
      auxin, ethylene, cytokinin, brassinosteroid, and jasmonate. A high-sensitivity
      analysis revealed a surprisingly low number of common target genes. Instead,
      different hormones appear to regulate distinct members of protein families. We
      conclude that there is not a core transcriptional growth-regulatory module in
      young Arabidopsis seedlings.

PMID- 16901782
TI  - Clonal origin and evolution of a transmissible cancer.
AB  - The transmissible agent causing canine transmissible venereal tumor (CTVT) is
      thought to be the tumor cell itself. To test this hypothesis, we analyzed genetic
      markers including major histocompatibility (MHC) genes, microsatellites, and
      mitochondrial DNA (mtDNA) in naturally occurring tumors and matched blood
      samples. In each case, the tumor is genetically distinct from its host. Moreover,
      tumors collected from 40 dogs in 5 continents are derived from a single
      neoplastic clone that has diverged into two subclades. Phylogenetic analyses
      indicate that CTVT most likely originated from a wolf or an East Asian breed of
      dog between 200 and 2500 years ago. Although CTVT is highly aneuploid, it has a
      remarkably stable genotype. During progressive growth, CTVT downmodulates MHC
      antigen expression. Our findings have implications for understanding genome
      instability in cancer, natural transplantation of allografts, and the capacity of
      a somatic cell to evolve into a transmissible parasite.

PMID- 16901783
TI  - Beta 4 integrin amplifies ErbB2 signaling to promote mammary tumorigenesis.
AB  - Amplification of the ErbB2 locus, which encodes a receptor tyrosine kinase, is
      common in aggressive breast tumors and correlates with poor prognosis. The
      mechanisms underlying ErbB2-mediated breast carcinoma progression remain
      incompletely defined. To examine the role of the signaling and cell-adhesion
      receptor beta 4 integrin during ErbB2-mediated tumorigenesis, we introduced a
      targeted deletion of the beta 4 signaling domain into a mouse model of ErbB2
      induced mammary carcinoma. Loss of beta 4 signaling suppresses mammary tumor
      onset and invasive growth. Ex vivo studies indicate that beta 4 forms a complex
      with ErbB2 and enhances activation of the transcription factors STAT3 and c-Jun.
      STAT3 contributes to disruption of epithelial adhesion and polarity, while c-Jun
      is required for hyperproliferation. Finally, deletion of the beta 4 signaling
      domain enhances the efficacy of ErbB2-targeted therapy. These results indicate
      that beta 4 integrin promotes tumor progression by amplifying ErbB2 signaling and
      identify beta 4 as a potential target for molecular therapy of breast cancer.

PMID- 16901784
TI  - A novel role for high-mobility group a proteins in cellular senescence and
      heterochromatin formation.
AB  - Cellular senescence is a stable state of proliferative arrest that provides a
      barrier to malignant transformation and contributes to the antitumor activity of
      certain chemotherapies. Senescent cells can accumulate senescence-associated
      heterochromatic foci (SAHFs), which may provide a chromatin buffer that prevents
      activation of proliferation-associated genes by mitogenic transcription factors.
      Surprisingly, we show that the High-Mobility Group A (HMGA) proteins, which can
      promote tumorigenesis, accumulate on the chromatin of senescent fibroblasts and
      are essential structural components of SAHFs. HMGA proteins cooperate with the
      p16(INK4a) tumor suppressor to promote SAHF formation and proliferative arrest
      and stabilize senescence by contributing to the repression of proliferation
      associated genes. These antiproliferative activities are canceled by coexpression
      of the HDM2 and CDK4 oncogenes, which are often coamplified with HMGA2 in human
      cancers. Our results identify a component of the senescence machinery that
      contributes to heterochromatin formation and imply that HMGA proteins also act in
      tumor suppressor networks.

PMID- 16901785
TI  - Real-time observation of RecA filament dynamics with single monomer resolution.
AB  - RecA and its homologs help maintain genomic integrity through recombination.
      Using single-molecule fluorescence assays and hidden Markov modeling, we show the
      most direct evidence that a RecA filament grows and shrinks primarily one monomer
      at a time and only at the extremities. Both ends grow and shrink, contrary to
      expectation, but a higher binding rate at one end is responsible for directional
      filament growth. Quantitative rate determination also provides insights into how
      RecA might control DNA accessibility in vivo. We find that about five monomers
      are sufficient for filament nucleation. Although ordinarily single-stranded DNA
      binding protein (SSB) prevents filament nucleation, single RecA monomers can
      easily be added to an existing filament and displace SSB from DNA at the rate of
      filament extension. This supports the proposal for a passive role of RecA-loading
      machineries in SSB removal.

PMID- 16901786
TI  - A role for the deubiquitinating enzyme USP28 in control of the DNA-damage
      response.
AB  - The Chk2-p53-PUMA pathway is a major regulator of DNA-damage-induced apoptosis in
      response to double-strand breaks in vivo. Through analysis of 53BP1 complexes we
      have discovered a new ubiquitin protease, USP28, which regulates this pathway.
      Using a human cell line that faithfully recapitulated the Chk2-p53-PUMA pathway,
      we show that USP28 is required to stabilize Chk2 and 53BP1 in response to DNA
      damage. In this cell line, both USP28 and Chk2 are required for DNA-damage
      induced apoptosis, and they accomplish this in part through regulation of the p53
      induction of proapoptotic genes like PUMA. Our studies implicate DNA-damage
      induced ubiquitination and deubiquitination as a major regulator of the DNA
      damage response for Chk2, 53BP1, and a number of other proteins in the DNA-damage
      checkpoint pathway, including several mediators, such as Mdc1, Claspin, and
      TopBP1.

PMID- 16901787
TI  - Rules for nuclear localization sequence recognition by karyopherin beta 2.
AB  - Karyopherinbeta (Kapbeta) proteins bind nuclear localization and export signals
      (NLSs and NESs) to mediate nucleocytoplasmic trafficking, a process regulated by
      Ran GTPase through its nucleotide cycle. Diversity and complexity of signals
      recognized by Kap betas have prevented prediction of new Kap beta substrates. The
      structure of Kap beta 2 (also known as Transportin) bound to one of its
      substrates, the NLS of hnRNP A1, that we report here explains the mechanism of
      substrate displacement by Ran GTPase. Further analyses reveal three rules for NLS
      recognition by Kap beta 2: NLSs are structurally disordered in free substrates,
      have overall basic character, and possess a central hydrophobic or basic motif
      followed by a C-terminal R/H/KX(2-5)PY consensus sequence. We demonstrate the
      predictive nature of these rules by identifying NLSs in seven previously known
      Kap beta 2 substrates and uncovering 81 new candidate substrates, confirming five
      experimentally. These studies define and validate a new NLS that could not be
      predicted by primary sequence analysis alone.

PMID- 16901788
TI  - A segmentation gene in tribolium produces a polycistronic mRNA that codes for
      multiple conserved peptides.
AB  - Segmentation genes in insects are required for generating the subdivisions of the
      early embryo. We describe here a new member of the gap family of segmentation
      genes in the flour beetle Tribolium, mille-pattes (mlpt). mlpt knockdown leads to
      transformation of the abdominal segments into thoracic segments, providing
      embryos with up to ten pairs of legs. We show that there are crossregulatory
      interactions between mlpt and the known gap genes in Tribolium, suggesting that
      mlpt is itself a gap gene. The mlpt gene reveals an unusual structure, as it
      encodes a polycistronic mRNA that codes for four peptides. mlpt appears to be the
      prototype of this previously unknown gene structure in eukaryotes, as we find
      homologous genes with the same polycistronic arrangement in other insect genomes
      as well.

PMID- 16901789
TI  - Sequential quality-control checkpoints triage misfolded cystic fibrosis
      transmembrane conductance regulator.
AB  - Cystic fibrosis arises from the misfolding and premature degradation of CFTR
      Delta F508, a Cl- ion channel with a single amino acid deletion. Yet, the quality
      control machinery that selects CFTR Delta F508 for degradation and the mechanism
      for its misfolding are not well defined. We identified an ER membrane-associated
      ubiquitin ligase complex containing the E3 RMA1, the E2 Ubc6e, and Derlin-1 that
      cooperates with the cytosolic Hsc70/CHIP E3 complex to triage CFTR and CFTR Delta
      F508. Derlin-1 serves to retain CFTR in the ER membrane and interacts with RMA1
      and Ubc6e to promote CFTR's proteasomal degradation. RMA1 is capable of
      recognizing folding defects in CFTR Delta F508 coincident with translation,
      whereas the CHIP E3 appears to act posttranslationally. A folding defect in CFTR
      Delta F508 detected by RMA1 involves the inability of CFTR's second membrane
      spanning domain to productively interact with amino-terminal domains. Thus, the
      RMA1 and CHIP E3 ubiquitin ligases act sequentially in ER membrane and cytosol to
      monitor the folding status of CFTR and CFTR Delta F508.

PMID- 16901790
TI  - Blimp1 defines a progenitor population that governs cellular input to the
      sebaceous gland.
AB  - Epidermal lineage commitment occurs when multipotent stem cells are specified to
      three lineages: the epidermis, the hair follicle, and the sebaceous gland (SG).
      How and when a lineage becomes specified remains unknown. Here, we report the
      existence of a population of unipotent progenitor cells that reside in the SG and
      express the transcriptional repressor Blimp1. Using cell-culture studies and
      genetic lineage tracing, we demonstrate that Blimp1-expressing cells are upstream
      from other cells of the SG lineage. Blimp1 appears to govern cellular input into
      the gland since its loss leads to elevated c-myc expression, augmented cell
      proliferation, and SG hyperplasia. Finally, BrdU labeling experiments demonstrate
      that the SG defects associated with loss of Blimp1 lead to enhanced bulge stem
      cell activity, suggesting that when normal SG homeostasis is perturbed,
      multipotent stem cells in the bulge can be mobilized to correct this imbalance.

PMID- 16901792
TI  - Prevalence and predictors of corticosteroid-related hyperglycemia in hospitalized
      patients.
AB  - OBJECTIVE: To investigate the prevalence of and risk factors for hyperglycemia in
      hospitalized patients receiving corticosteroids, which have been identified as an
      independent predictor of hyperglycemia. METHODS: We conducted a retrospective
      review of electronic medical records of patients admitted to the general medicine
      service at a university hospital during a 1-month period. Pharmacy charges were
      used to identify patients receiving high doses (> or = 40 mg/day of prednisone or
      the equivalent) of corticosteroids for at least 2 days. Occurrence of
      hyperglycemia and the presence of risk factors, including history of diabetes,
      duration of corticosteroid therapy, concurrent parenteral nutrition, antibiotic
      therapy, use of medications associated with hyperglycemia, severity of illness
      scores, and hospital length of stay, were determined. Patients experiencing
      multiple episodes of hyperglycemia (glucose levels > or = 200 mg/dL) were
      compared with those who had < or = 1 hyperglycemic episode. Patients without a
      history of diabetes were assessed separately. RESULTS: During the 1-month study
      period, 66 of 617 patients received high doses of corticosteroids, but only 50 of
      the 66 had glucose measurements. Hyperglycemia was documented in 32 of these 50
      patients (64%), and multiple hyperglycemic episodes occurred in 26 (52%). A
      history of diabetes was documented in 12 of 26 patients who experienced multiple
      episodes, in comparison with 4 of 24 patients with < or = 1 episode of
      hyperglycemia (P = 0.035). Among patients without a history of diabetes, 19 of 34
      (56%) had hyperglycemia at least once. Patients with multiple episodes of
      hyperglycemia had more comorbid diseases, longer duration of corticosteroid
      therapy, and longer duration of hospital stay. CONCLUSION: Hyperglycemia occurs
      in a majority of hospitalized patients receiving high doses of corticosteroids.
      In light of the poor outcomes associated with hyperglycemia, protocols targeting
      its detection and management should be available for patients who receive
      corticosteroid therapy.

PMID- 16901791
TI  - Exploring the mode-of-action of bioactive compounds by chemical-genetic profiling
      in yeast.
AB  - Discovering target and off-target effects of specific compounds is critical to
      drug discovery and development. We generated a compendium of "chemical-genetic
      interaction" profiles by testing the collection of viable yeast haploid deletion
      mutants for hypersensitivity to 82 compounds and natural product extracts. To
      cluster compounds with a similar mode-of-action and to reveal insights into the
      cellular pathways and proteins affected, we applied both a hierarchical
      clustering and a factorgram method, which allows a gene or compound to be
      associated with more than one group. In particular, tamoxifen, a breast cancer
      therapeutic, was found to disrupt calcium homeostasis and phosphatidylserine (PS)
      was recognized as a target for papuamide B, a cytotoxic lipopeptide with anti-HIV
      activity. Further, the profile of crude extracts resembled that of its
      constituent purified natural product, enabling detailed classification of extract
      activity prior to purification. This compendium should serve as a valuable key
      for interpreting cellular effects of novel compounds with similar activities.

PMID- 16901793
TI  - Trends in lipid management among patients with diabetes.
AB  - OBJECTIVE: To examine trends in lipid management (cholesterol testing, treatment,
      and goal attainment) among patients with diabetes and to analyze the factors
      associated with initiation of lipid-lowering therapy. METHODS: We conducted a
      longitudinal, retrospective study of patients with diabetes identified during a
      24-month baseline period (January 1, 1995, to December 31, 1996) and for whom
      follow-up was continued for 5 years (1997 to 2001). Generalized estimating
      equations were used to test for time trend effects in lipid management. We
      modeled the days from baseline to the first lipid-lowering prescription fill date
      with a multivariate Cox proportional hazards regression model. RESULTS: Rates of
      lipid testing, treatment, and goal attainment significantly improved (P<0.001)
      during the 5-year study period: from 37% to 67% for lipid testing; from 19% to
      41% for treatment with a lipid-lowering agent; from 22% to 37% for achievement of
      low-density lipoprotein cholesterol (LDL-C) levels < 100 mg/dL; and from 54% to
      75% for achievement of LDL-C levels < 130 mg/dL. The relative likelihood (hazard
      rate) of treatment with lipid-lowering agents was greater for patients with LDL-C
      levels > or = 100 mg/dL relative to patients with LDL-C concentrations < 100
      mg/dL. Treatment with lipid-lowering agents of patients with a cardiovascular
      event during follow-up was approximately 3 times more likely relative to those
      without such an event. CONCLUSION: We found that rates of lipid testing,
      treatment, and goal attainment improved significantly between 1997 and 2001.
      Nevertheless, ample room for improvement of these rates continues to exist.
      Particular attention may be warranted to ensure that patients with diabetes
      receive lipid-lowering agents not only after a cardiovascular event but also
      before such an event occurs.

PMID- 16901795
TI  - Graves' disease in the cervical thyroid and thyroglossal duct remnant: case
      report and review of literature.
AB  - OBJECTIVE: To describe a patient with a rare presentation of Graves' disease in
      the cervical thyroid and thyroglossal duct remnant. METHODS: We present a
      detailed case report, including initial manifestations, laboratory findings, and
      radiologic evaluation of a patient with Graves' disease. A review of the relevant
      medical literature is included. A search for articles in the MEDLINE database
      from 1966 to November 2003 was performed with use of the following key words:
      thyroglossal duct remnant, thyroglossal duct cyst, thyrotoxicosis, Graves'
      disease, hyperthyroidism, and ectopic thyroid tissue. The reference lists from
      the articles obtained from the MEDLINE database were then reviewed for other
      pertinent articles. English abstracts of non-English articles were also reviewed.
      RESULTS: A 63-year-old woman presented with thyrotoxicosis. Examination of her
      neck was notable for a 3.5-cm soft, mobile midline mass overlying the thyroid
      cartilage. She had no extrathyroidal manifestations of Graves' disease. The rest
      of the physical examination was unremarkable. Laboratory studies revealed a
      thyrotropin (thyroid-stimulating hormone) level of 0.01 microIU/mL (normal range,
      0.3 to 6.6) and free thyroxine level of 4.7 ng/dL (normal range, 0.6 to 1.5). An
      ultrasound study showed a normal-appearing thyroid and an infrahyoidal neck mass
      (3.0 by 1.7 cm). A radioiodine (123I) thyroid scan demonstrated diffuse
      homogeneous uptake throughout the gland in conjunction with 66.6% uptake at 24
      hours. In addition, a large rounded area of increased activity slightly left of
      the midline was noted. The left anterior oblique image showed that this area was
      not continuous with the left upper pole. We thought that this finding represented
      a hyperfunctioning thyroglossal duct cyst or remnant tissue. Our patient
      subsequently underwent radioiodine therapy with 15.56 mCi of 131I. A review of
      the English-language literature revealed only rare case reports of thyrotoxicosis
      in ectopic thyroid tissue. CONCLUSION: Although the occurrence of thyrotoxicosis
      is common, to the best of our knowledge this is only the second case of Graves'
      disease involving the thyroglossal duct remnant reported in the English
      literature.

PMID- 16901796
TI  - Calciphylaxis in the absence of end-stage renal disease.
AB  - OBJECTIVE: To report a case of calciphylaxis in the absence of renal failure in a
      patient with secondary hyperparathyroidism and low calcium/phosphorus product, in
      whom total parathyroidectomy resulted in relief of pain and healing of
      ulcerations. METHODS: We present the clinical, laboratory, and pathologic
      findings in a 62-year-old woman with calciphylaxis in the absence of end-stage
      renal disease. RESULTS: A 62-year-old woman presented with painful nonhealing
      bilateral calf ulcerations. Pathology examination of tissue specimens from
      surgical debridement revealed intravascular calcification, consistent with
      calciphylaxis. Laboratory investigation revealed normal renal function; however,
      hypocalcemia and hypophosphatemia were present--a corrected serum calcium level
      of 7.5 mg/dL (normal, 8.5 to 10.2) and a serum phosphorus value of 1.0 mg/dL
      (normal, 2.5 to 4.5). These abnormalities were likely due to vitamin D
      deficiency, evidenced by a 25-hydroxyvitamin D level of 14 ng/mL, which provoked
      an elevation of the serum parathyroid hormone (PTH) concentration, documented by
      an intact PTH of 213 pg/mL (normal, 15 to 65) and a whole PTH (1-84 PTH) of 70.6
      pg/mL (normal, 7 to 36). Her quality of life was severely impaired, not only by
      the ulcerations but also by intractable pain that necessitated epidural analgesia
      during the hospitalization. The patient underwent total parathyroidectomy and
      transcervical thymectomy, with cryopreservation of parathyroid tissue. One year
      after the parathyroidectomy, the patient had no recurrence of calciphylaxis.
      CONCLUSION: This case suggests that despite the potential complex
      pathophysiologic aspects of calciphylaxis, even in the absence of both renal
      failure and an elevated calcium/phosphorus product, early parathyroidectomy in
      patients with appreciably increased PTH levels may improve wound healing and
      diminish pain.

PMID- 16901794
TI  - Spectrum of malignant somatostatin-producing neuroendocrine tumors.
AB  - OBJECTIVE: To evaluate the clinical manifestations and outcome of patients with
      somatostatinomas--rare neuroendocrine tumors of pancreaticoduodenal origin.
      METHODS: We searched the medical archives and tumor registry of our institution
      for somatostatinomas or somatostatin-staining tumors for the 12-year period from
      January 1990 to February 2002. In addition, we reviewed laboratory databases for
      patients who had an elevated serum somatostatin level. Patients with a
      neuroendocrine tumor and an elevated serum somatostatin level or somatostatin
      positive tumor immunostaining were included in this study. RESULTS: Eleven
      patients qualified (9 men and 2 women; median age at diagnosis, 45 years; age
      range, 22 to 73). The diagnosis of a somatostatinoma was made by immunostaining
      of the tumor in 9 patients and by finding elevated serum somatostatin levels in
      2. Five primary tumors were of duodenal and 6 of pancreatic origin. Psammoma body
      formation and association with neurofibromatosis were seen only in the duodenal
      tumors. The known primary tumor sizes varied from 2 to 6 cm. Liver metastatic
      lesions were present in 6 patients, abdominal lymph node involvement was found in
      10 patients, and lung, spleen, and ovarian metastatic involvement was noted in 1
      patient each. Diabetes was present in 4 patients (36%) and cholelithiasis in 7
      (64%). The presence of a mass led to the diagnosis in most patients with primary
      duodenal tumors, whereas patients with pancreatic tumors were more likely to have
      endocrine manifestations. A Whipple procedure was performed in 6 patients, distal
      pancreatectomy in 3, hepatic artery embolization or ligation in 3, and partial
      hepatectomy in 1. Cancer-related death occurred in 4 patients, 1 to 8 years after
      diagnosis (median, 4.5 years). At last follow-up, 2 patients were alive without
      evidence of disease (8 and 10 years after diagnosis), and 3 were alive with liver
      metastatic lesions. The status of 2 patients was unclear. CONCLUSION:
      Somatostatinomas occurred with approximately equal frequency in the duodenum and
      the pancreas. The duodenal tumors were more likely to be pure somatostatinomas
      and have psammoma bodies. Pancreatic tumors were more likely to be multihormonal.
      Cholelithiasis and diabetes were seen in 64% and 36%, respectively, of the
      patients. Mass effect of the tumor was the usual manifestation leading to
      diagnosis. These tumors are slow growing, and long-term survival is possible.

PMID- 16901797
TI  - Metastatic malignant insulinoma in a patient with type 2 diabetes mellitus: case
      presentation and literature review.
AB  - OBJECTIVE: To describe the occurrence of metastatic malignant insulinoma in a
      patient with preexisting type 2 diabetes mellitus. METHODS: We present a detailed
      case report, with clinical, biochemical, and imaging findings, and summarize the
      data from 21 similar cases in the literature. RESULTS: The occurrence of
      malignant insulinoma in a patient with preexisting diabetes is very rare and thus
      can be a diagnostic challenge. In our patient with type 2 diabetes, endogenous
      hyperinsulinism was confirmed by demonstrating elevated insulin and C-peptide
      levels during hypoglycemic episodes in the absence of sulfonylurea on a blood
      screen. Abdominal computed tomographic scan and magnetic resonance imaging
      revealed a pancreatic mass as well as metastatic lesions in the liver. The
      pancreatic mass was removed and confirmed to be a malignant insulinoma. This
      procedure was followed by disappearance of the hypoglycemic episodes as well as
      the diabetes for a few months. On follow-up, however, more metastatic lesions
      appeared in conjunction with a protracted course of hypoglycemia that
      necessitated treatment with antihypoglycemic agents and, 3 years after the
      initial surgical intervention, culminated in the death of the patient.
      CONCLUSION: Our patient is one of the few subjects known to have a malignant
      insulinoma in conjunction with preexisting diabetes. A high degree of suspicion
      for the presence of an insulinoma should be maintained when unexplained
      hypoglycemic episodes occur in a patient with previously stable diabetes.

PMID- 16901798
TI  - Multiple ovarian cysts and oligomenorrhea as the initial manifestations of a
      gonadotropin-secreting pituitary macroadenoma.
AB  - OBJECTIVE: To report a case of a follicle-stimulating hormone (FSH)-secreting
      pituitary adenoma, which manifested with oligomenorrhea, dysmenorrhea, and
      multiple bilateral ovarian cysts. METHODS: We present a case report of a 29-year
      old woman, including detailed laboratory, radiologic, and pathologic findings,
      who was diagnosed as having an FSH-secreting pituitary tumor. The pertinent
      literature is also reviewed. RESULTS: A 29-year-old woman, after experiencing
      oligomenorrhea and increasing abdominal girth for >1 year, presented with an
      acute abdomen. Ultrasonography revealed multicystic ovaries >15 cm in maximal
      diameter, causing bilateral adnexal torsion. After bilateral ovarian
      cystectomies, ultrasound study showed recurrence of the cysts. Relevant
      laboratory data were as follows: serum FSH 6.8 mIU/mL, luteinizing hormone 0.1
      mIU/mL, prolactin 67 ng/mL, human chorionic gonadotropin <2 mIU/mL, progesterone
      3.5 ng/dL, estradiol 237 pg/mL, thyrotropin 1.8 microIU/mL, testosterone <4
      ng/dL, insulin 8.0 microIU/mL, and fasting plasma glucose 87 mg/dL. Magnetic
      resonance imaging (MRI) of the brain revealed a 2.5-cm pituitary mass, although
      the patient had no symptoms of pituitary dysfunction. Transsphenoidal removal of
      the mass was performed, and pathology studies were positive for FSH-secreting
      adenoma. Repeated MRI at 3 months showed an 0.8-cm residual tumor. The patient
      refused adjuvant radiotherapy. Regular menses resumed within 2 months
      postoperatively, and she later successfully became pregnant. Almost 3 years after
      treatment, the patient remained asymptomatic, results of pituitary function tests
      were normal, and follow-up MRI showed no signs of tumor regrowth. CONCLUSION:
      Although very uncommon, gonadotropin-secreting pituitary adenomas should be
      considered in the differential diagnosis of new-onset oligomenorrhea and
      dysmenorrhea, especially if associated with multicystic ovaries on ultrasound
      study, even in the absence of elevated levels of serum gonadotropins.
      Furthermore, we propose that it may be acceptable to withhold adjuvant
      radiotherapy in patients who are asymptomatic after transsphenoidal surgical
      excision of these tumors.

PMID- 16901799
TI  - Diagnostic challenge of glucagonoma: case report and literature review.
AB  - OBJECTIVE: To report the diagnostic difficulties encountered in a case of
      glucagonoma. METHODS: We provide a literature review and present the clinical
      findings, pertinent laboratory data, and results of related studies in a patient
      with a glucagonoma. RESULTS: A 54-year-old-man, with no relevant history of
      endocrine disorders, presented to the hospital with a 5-year history of recurrent
      stomatitis and glossitis, a more recent weight loss of 11.5 kg, and recurrent
      pruritic maculae on the scalp in conjunction with raised erythematous maculae in
      the scrotal region and perineum that gradually migrated to the distal
      extremities, becoming bullous and painful. The patient was hospitalized, and
      because of the dermatologic findings suggestive of necrolytic migratory erythema,
      the presence of a glucagonoma was suspected. His blood glucose levels were in the
      normal range. Glucagon levels were found to be elevated, and imaging studies
      confirmed the presence of an enlarged mass in the pancreatic tail, without
      evidence of extension to surrounding structures. Liver metastatic lesions were
      also excluded. After surgical removal of the tumor, the skin and oral mucosal
      lesions disappeared spontaneously. The histologic appearance and
      immunohistochemical staining results confirmed the diagnosis of a glucagonoma.
      Subsequently, all related symptoms resolved, and the glucagon levels normalized.
      CONCLUSION: The diagnosis of glucagonoma is often delayed. Clinicians should be
      aware of the unusual initial manifestations of this tumor and the potential for
      less than a full spectrum of the characteristic features of the glucagonoma
      syndrome.

PMID- 16901800
TI  - Thyrotoxic periodic paralysis in a Hispanic man after the administration of
      prednisone.
AB  - OBJECTIVE: To present a case of thyrotoxic periodic paralysis (TPP) in a Hispanic
      man and to discuss the potential precipitating mechanisms. METHODS: We review the
      clinical and laboratory findings relative to the occurrence of TPP in a 34-year
      old Hispanic man, who had been diagnosed as having Graves' disease. RESULTS: TPP
      is a rare complication of thyrotoxicosis. The two known triggers of TPP are high
      carbohydrate intake and rest after strenuous physical activity. Other
      precipitating factors include ingestion of alcohol, infection, trauma, emotional
      stress, and exposure to cold. Nonselective beta-adrenergic blocking agents are
      used as prophylaxis for the paralytic attacks. Glucocorticoids have been used to
      treat nonresponsive and recurrent episodes. Nevertheless, our patient, a 34-year
      old Hispanic man, had received propranolol for 7 days and one single dose of
      prednisone 2 hours before the onset of the paralysis. In patients with TPP, the
      Na+/K+-adenosinetriphosphatase (ATPase) pump activity is considerably increased
      by excess thyroid hormones, resulting in an increased intracellular potassium
      shift. Insulin activates the Na+/K+-ATPase pump as well; thus, the precipitating
      effect of a high carbohydrate diet is explained. Glucocorticoids have been shown
      to increase the number of Na+/K+-ATPase molecules in skeletal muscle. They also
      increase insulin secretion in the basal state and the first-phase insulin release
      after a glucose load. CONCLUSION: In our patient with TPP, the onset of the
      attack was not prevented by the use of propranolol and was likely triggered by
      the administration of prednisone.

PMID- 16901801
TI  - Inferior laryngeal paraganglioma mimicking a primary thyroid tumor.
AB  - OBJECTIVE: To report an unusual case of inferior laryngeal paraganglioma that
      manifested as a thyroid neoplasm. METHODS: A case report is presented, including
      ultra-sonographic, surgical, histologic, and immunohistochemical findings, and
      diagnostic and therapeutic strategies are discussed. RESULTS: In a 33-year-old
      man with a mass in the left side of his neck, color Doppler ultrasonography
      revealed an extremely hypervascular lesion that appeared to arise in the left
      lobe of the thyroid gland. Fine-needle aspiration was noncontributory because of
      bloody samples, but core biopsy specimens suggested a nonthyroidal neoplasm. At
      surgical intervention, a 3.5-cm mass was found immediately posterior to the left
      thyroid lobe, not involving the thyroid capsule. Because the mass could not be
      dissected free from the thyroid, performance of a left thyroid lobectomy and
      isthmectomy was necessary. The pathology specimen was a paraganglioma.
      CONCLUSION: Paragangliomas may be sonographically similar to thyroid neoplasms
      and may be included in the differential diagnosis of a hypervascular thyroid
      mass.

PMID- 16901802
TI  - Secondary osteoporosis: a review of the recent evidence.
AB  - OBJECTIVE: To review several causes of secondary osteoporosis as well as
      screening recommendations for underlying disorders. METHODS: We conducted a
      review of the literature on many of the causes of osteoporosis that have been
      published during the past 15 years, focusing on those sources available from 2000
      through the present. Indeed, more than two-thirds of the articles that we
      reviewed were printed during the past 6 years. These reports examined secondary
      osteoporosis in general, as well as many of the specific causes. RESULTS:
      Secondary osteoporosis occurs in almost two-thirds of men, more than half of
      premenopausal and perimenopausal women, and about one-fifth of postmenopausal
      women. Its causes are vast, and they include hypogonadism, medications,
      hyperthyroidism, vitamin D deficiency, primary hyperparathyroidism, solid organ
      transplantation, gastrointestinal diseases, hematologic diseases, Cushing's
      syndrome, and idiopathic hypercalciuria. These causes have their own
      pathogenesis, epidemiologic features, and effect on the skeleton. CONCLUSION: The
      causes of secondary osteoporosis are numerous, and an understanding of their
      characteristics with respect to bone density and potential fracture risk is
      essential in the management of osteoporosis. A heightened awareness of the
      possibility of their existence is necessary to provide optimal care.

PMID- 16901803
TI  - Hyponatremia, fluid-electrolyte disorders, and the syndrome of inappropriate
      antidiuretic hormone secretion: diagnosis and treatment options.
AB  - OBJECTIVE: To review the types and causes of hyponatremia and examine the various
      strategies for treatment of this disorder. METHODS: A systematic review of the
      current literature is provided, targeting endocrinology clinicians who consult
      with hospital medical and surgical staff when managing patients with
      hyponatremia. Treatment for euvolemic and hypervolemic hyponatremia with arginine
      vasopressin receptor antagonists is presented, which provides a new treatment
      option for patients with disorders of water metabolism. RESULTS: Hyponatremia is
      recognized as the most common electrolyte disorder encountered in the clinical
      setting and is associated with a variety of conditions including dilutional
      disorders, such as congestive heart failure and the syndrome of inappropriate
      antidiuretic hormone secretion, and depletional disorders, such as diarrhea and
      vomiting or blood loss. Most cases of mild hyponatremia can be treated
      effectively. Acute, severe hyponatremia that is untreated or treated
      ineffectively, however, can lead to serious neurologic outcomes or death. With
      the poor prognosis for morbidity and mortality in patients with severe
      hyponatremia, hospital-based clinicians must identify those at risk for
      hyponatremia and suggest appropriate treatment intervention. A new class of
      drugs, the arginine vasopressin receptor antagonists, targets receptors on
      collecting duct cells of the nephron and causes aquaresis, the excretion of free
      water. This therapy leads to the restoration of sodium-water homeostasis in
      patients with euvolemic and hypervolemic hyponatremia. CONCLUSION: With many
      hospitalized patients at risk for hyponatremia, especially elderly patients in
      critical care and postsurgical units, identification of involved patients,
      recommendation of appropriate treatment, and awareness of new therapeutic options
      are critical.

PMID- 16901804
TI  - Games of hormones: the para-endocrinology of sport.

PMID- 16901805
TI  - Idle thoughts from an addled mind. One size fits all.

PMID- 16901806
TI  - Visual vignette. Hyperthyroidism and cystic thyroid mass.

PMID- 16901807
TI  - Two new insecticidal sesquiterpene polyol esters from Celastrus angulatus.
AB  - Two new insecticidal sesquiterpene polyol esters with a beta-dihydroagarofuran
      sesquiterpene skeleton, celangulatin A (1), B (2), and two known compounds,
      celangulin IV (3) and V (4), were isolated from the leaves of Celastrus angulatus
      by bioassay-guided fractionation. Their chemical structures were elucidated
      mainly by analyses of the NMR and MS spectral data. Their insecticidal activities
      against Mythimna separate were demonstrated with the KD50 value of 68.5 and 215.8
      microg g(-1), respectively.

PMID- 16901808
TI  - Two new bioactive sesquiterpenes from the soft coral Sinularia sp.
AB  - Two new sesquiterpenes, 1S*, 4R*, 5S*, 6R*, 7S*, 10S*-1(5), 6(7)-diepoxy-4-guaiol
      (1) and 1S*, 4S*, 5S*, 10R*-4,10-guaianediol (2) have been isolated from the
      ethyl acetate soluble portion of the soft coral Sinularia sp., and their
      stereostructure were determined by spectroscopic methods and by X-ray single
      crystal analysis. Both compounds showed antioxidant and cytotoxic activities.

PMID- 16901809
TI  - Potent tyrosinase inhibitors from Trifolium balansae.
AB  - Trifolium balansae (Leguminosae) yielded a phytylester, phytyl-1-hexanoate, three
      steroids, stigmast-5-ene-3 beta,26-diol, stigmast-5-ene-3-ol and campesterol, and
      an alcohol, pentacosanol which were reported for the first time from T.balansae.
      The structures of the isolates were determined by 1D and 2D NMR techniques and MS
      spectroscopy. Compounds 1-5 were tested for their enzyme tyrosinase activity.
      While compounds 1 and 5 did not show any inhibition against the enzyme
      tyrosinase, compounds 2, 3, and 4 exhibited potent inhibition against tyrosinase.
      Highly potent (IC50 = 2.39 microM) inhibition was found by compound 2, when
      compared with the standard tyrosinase inhibitors Kojic acid and L-mimosine.

PMID- 16901810
TI  - Suppression of MeIQ-induced SOS response by allylbenzenes from Asiasarum
      heterotropoides in the Salmonella typhimurium OY1001/1A2 umu test.
AB  - Three allylbenzenes from Asiasarum heterotropoides, methyleugenol (1), elemicin
      (2) and gamma-asaron (3) showed suppressive effects on umu gene expression of the
      SOS response in the Salmonella typhimurium OY1001/1A2 umu test against the
      mutagen 2-amino-3,4-dimethylimidazo[4,5-f ]quinoline (MeIQ). Gene expression was
      suppressed 70.0, 75.9 and 81.7% at a concentration of 0.4 mM, respectively. The
      ID50 values (50% inhibition dose) of these compounds were 0.125, 0.098 and 0.059
      mM, respectively. On the other hand, compounds 1-3 showed weak suppressive
      effects of the SOS-inducing activity on activated MeIQ.

PMID- 16901811
TI  - A new anti-oxidant Diels-Alder type adduct from Morus macroura.
AB  - A new Diels-Alder type adduct, named guangsangon O, was isolated from Morus
      macroura Miq., and its structure was determined by means of spectroscopic
      analyses and chemical methods. The isolated new compound showed potent anti
      oxidant activity in vitro.

PMID- 16901812
TI  - Anti-inflammatory sesquiterpenes from Curcuma zedoaria.
AB  - From the methanolic extract of the rhizome of Curcuma zedoaria, we isolated anti
      inflammatory sesquiterpene furanodiene (1) and furanodienone (2) along with new
      sesquiterpene compound 3 and known eight sesquiterpenes, zederone (4),
      curzerenone (5), curzeone (6), germacrone (7), 13-hydroxygermacrone (8),
      dehydrocurdione (9), curcumenone (10), and zedoaronediol (11). Their structures
      were elucidated on the basis of spectroscopic data. The anti-inflammatory effect
      of isolated components on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced
      inflammation of mouse ears were examined. Compounds 1 and 2 suppressed the TPA
      induced inflammation of mouse ears by 75% and 53%, respectively, at a dose of 1.0
      micromol. Their activities are comparable to that of indomethacin, the normally
      used anti-inflammatory agent.

PMID- 16901813
TI  - Phosphodiesterase-I inhibitor quinovic acid glycosides from Bridelia ndellensis.
AB  - Quinovic acid-3-O-alpha-L-rhamnopyranoside (1), quinovic acid-3-O-beta-D
      fucopyranoside (2), quinovic acid-3-O-beta-D-glucopyranosyl (1 --> 4)-beta-D
      fucopyranoside (3), methyl gallate (4) and ethyl gallate (5) were isolated from
      the ethyl acetate extract of Bridelia ndellensis barks by fractionation.
      Compounds 1-3 showed significant inhibitory activity against snake venom
      phosphodiesterase-I.

PMID- 16901815
TI  - Synthesis of 2'-amino-LNA purine nucleosides.
AB  - The first reported synthesis of 2'-amino-LNA purine nucleosides via a
      transnucleosidation is accomplished enabling the preparation of oligonucleotides
      incorporating 2'-amino-LNA with all four natural bases.

PMID- 16901814
TI  - Anti-Salmonella activity of constituents of Ardisia elliptica Thunb.
AB  - Antibacterial activity against veterinary Salmonella was determined using dried
      fruit extracts of Ardisia elliptica Thunb. Chromatographic purification and
      spectroscopic structure studies provided three active anti-Salmonella compounds,
      namely, syringic acid, isorhamnetin and quercetin. The minimal inhibitory
      concentrations (MICs) of the isolated compounds ranged between 15.6 and 125.0
      microg mL(-1).

PMID- 16901816
TI  - Synthesis and antiviral activity of some C2-, C4-, and C6-substituted
      pyrazolo[3,4-D]pyrimidine acyclonucleosides with the alkylating chains of ACV,
      HBG, and ISO-DHPG.
AB  - A useful route to obtain trisubstituted pyrazolo[3,4-d]pyrimidines 14-17 is
      described. Those later were coupled with the alkylating agents 18-20 as in ACV,
      HBG, and iso-DHPG to give, after deprotection, the desired acylonucleosides 33
      44. Almost all of the new compounds were evaluated for their inhibitory effects
      against the replication of various DNA viruses in culture.

PMID- 16901817
TI  - Boronated thymidine analogues for boron neutron capture therapy.
AB  - Concise synthetic methods for synthesizing 3-carboranyl thymidine analogues
      (3CTAs) modified with cyclic and acyclic alcohols have been developed. The
      synthesis of these potential boron neutron capture therapy (BNCT) agents and
      their preliminary biological evaluation is described.

PMID- 16901818
TI  - Investigation of 1,3-dipolar cycloaddition reactions of unsaturated nitrones in
      ionic liquids.
AB  - The effect of the media (achiral and chiral ionic liquids) on the stereochemistry
      of intramolecular 1,3-dipolar cycloaddition reactions of D-galactose-derived
      omega-unsaturated nitrones, leading to bicyclic isoxazolidines, has been
      investigated.

PMID- 16901819
TI  - Simple synthesis and anti-HIV activity of novel 3'-vinyl branched apiosyl
      pyrimidine nucleosides.
AB  - Novel vinyl branched apiosyl nucleosides were synthesized in this study. Apiosyl
      sugar moiety was constructed by sequential ozonolysis and reductions. The bases
      (uracil and thymine) were efficiently coupled by glycosyl condensation procedure
      (persilyated base and TMSOTf). The antiviral activities of the synthesized
      compounds were evaluated against the HIV-1, HSV-1, HSV-2, and HCMV. Compound
      10beta displayed moderate anti-HIV activity (EC50 = 17.3 microg/mL) without
      exhibiting any cytotoxicity up to 100 microM.

PMID- 16901820
TI  - Simple synthesis of novel acyclic (e)-bromovinyl nucleosides as potential
      antiviral agents.
AB  - In these study, novel acyclic (E)-bromovinyl nucleosides were synthesized as
      potential antiviral agents. The coupling of the allylic bromide 9 with bases
      (thymine, uracil, 5-fluorouracil, 5-iodouracil, cytosine, adenine) afforded a
      series of novel acyclic nucleosides. The synthesized compounds were evaluated for
      their antiviral activity against various viruses such as HIV-1, HSV-1, HSV-2, and
      HCMV. 5-Iodouracil analogue 19 showed weak anti-HIV-1 activity.

PMID- 16901821
TI  - Chemically modified short interfering hybrids (siHYBRIDS): nanoimmunoliposome
      delivery in vitro and in vivo for RNAi of HER-2.
AB  - A blunt-ended 19-mer short interfering hybrid (siHybrid) (H) comprised of sense
      DNA/antisense-RNA targeting HER-2 mRNA was encapsulated in a liposomal nanoplex
      with anti-transferrin receptor single-chain antibody fragment (TfRscFv) as the
      targeting moiety for clinically relevant tumor-specific delivery. In vitro
      delivery to a human pancreatic cell line (PANC-1) was shown to exhibit sequence
      specific inhibition of 48-h cell growth with an IC50 value of 37 nM. The
      inhibitory potency of this siHybrid was increased (IC50 value of 7.8 nM) using a
      homologous chemically modified siHybrid (mH) in which the 19-mer sense strand had
      the following pattern of 2 '-deoxyinosine (dI) and 2 '-O-methylribonucleotide (2
      '-OMe) residues: 5'-d(TITIT)-2'OMe(GCGGUGGUU)-d(GICIT). These modifications were
      intended to favor antisense strand-mediated RNAi while mitigating possible sense
      strand-mediated off-target effects and RNase H-mediated cleavage of the antisense
      RNA strand. The presently reported immunoliposomal delivery system was
      successfully used in vivo to inhibit HER-2 expression, and thus induce apoptosis
      in human breast carcinoma tumors (MDA-MB-435) in mice upon repeated i.v.
      treatment at a dose of 3 mg/kg of H or mH. The in vivo potency of modified
      siHybrid mH appeared to be qualitatively greater than that of H, as was the case
      in vitro.

PMID- 16901823
TI  - Synthesis of 2-bromomethyl-3-hydroxy-2-hydroxymethyl-propyl pyrimidine and
      theophylline nucleosides under microwave irradiation. Evaluation of their
      activity against hepatitis B virus.
AB  - Alkylation of 2-methylthiopyrimidin-4(1H)-one (1a) and its 5(6)-alkyl derivatives
      1b-d as well as theophylline (7) with 2,2-bis(bromomethyl)-1,3-diacetoxypropane
      (2) under microwave irradiation gave the corresponding acyclonucleosides 1-[(3
      acetoxy-2-acetoxymethyl-2-bromomethyl)prop-1-yl]-2-methyl-thio pyrmidin-4(1H)
      ones 3a-d and 7-[(3-acetoxy-2-acetoxymethyl-2-bromomethyl)prop-1-yl]theophylline
      (8), which upon further irradiation gave the double-headed acyclonucleosides 1,1
      '-[(2,2-diacetoxymethyl)-1,3-propylidene]-bis[(2-(methylthio)-pyrimidin-4(1H)
      ones] 4a-c, and 7,7 '-[(2,2-diacetoxymethyl)-1,3-propylidene]-bis(theophylline)
      (9). The deacetylated derivatives were obtained by the action of sodium
      methoxide. The activity of deacetylated nucleosides against Hepatitis B virus was
      evaluated. Compound 5b showed moderate inhibition activity against HBV with mild
      cytotoxicity.

PMID- 16901822
TI  - Trimethylguanosine nucleoside inhibits cross-linking between Snurportin 1 and m3G
      CAPPED U1 snRNA.
AB  - Macromolecular nuclear import is an energy-and signal-dependent process. The best
      characterized type of nuclear import consists of proteins carrying the classical
      NLS that is mediated by the heterodimeric receptor importin alpha/beta.
      Spliceosomal snRNPs U1, U2, U4, and U5 nuclear import depend both on the 5'
      terminal m3G (trimethylguanosine) cap structure of the U snRNA and the Sm core
      domain. Snurportin 1 recognizes the m3G-cap structure of m3G-capped U snRNPs. In
      this report, we show how a synthesized trimethylguanosine nucleoside affects the
      binding of Snurportin 1 to m3G-capped U1 snRNA in a UV-cross-linking assay. The
      data indicated that TMG nucleoside is an essential component required in the
      recognition by Snurportin 1, thus suggesting that interaction of Snurportin 1
      with U1 snRNA is not strictly dependent on the presence of the whole cap
      structure, but rather on the presence of the TMG nucleoside structure. These
      results indicate that the free nucleoside TMG could be a candidate to be an
      inhibitor of the interaction between Snurportin 1 and U snRNAs. We also show the
      behavior of free TMG nucleoside in in vitro U snRNPs nuclear import.

PMID- 16901824
TI  - Synthesis and antiviral evaluation of novel 5'-norcarboacyclic phosphonic acid
      nucleosides.
AB  - This article describes a very simple route for synthesizing a novel 5'
      norcarboacyclic nucleotides. The condensation of the mesylates 17 and 18 with the
      natural nucleosidic bases (A,U,T,C) under standard nucleophilic substitution
      (K2CO3, 18-Crown-6, DMF) and deprotection afforded the target nucleotide
      analogues 27-34. In addition, these compounds were evaluated for their antiviral
      properties against various viruses.

PMID- 16901825
TI  - Structure of the biologically relevant G-quadruplex in the c-MYC promoter.
AB  - The nuclease hypersensitivity element III1 (NHE III1) in the c-MYC promoter
      controls up to 80-90% of the transcriptional activity of this gene. We have
      demonstrated that the guanine-rich strand of the NHE III1 forms a G-quadruplex
      consisting of a mixture of four biologically relevant loop isomers that function
      as a silencer element. NMR studies have shown that these G-quadruplexes are
      propeller-type parallel structures consisting of three stacked G-tetrads and
      three double-chain reversal loops. An NMR-derived solution structure for this
      quadruplex provides insight into the unusual stability of the structure. This
      structure is a target for small molecule inhibitors of c-MYC gene expression.

PMID- 16901828
TI  - Evolutionary patterns in early tetrapods. I. Rapid initial diversification
      followed by decrease in rates of character change.
AB  - Although numerous studies have examined morphological diversification during
      major radiations of marine taxa, much less attention has been paid to terrestrial
      radiations. Here, we examine rates of character change over phylogeny and over
      time for Palaeozoic limbed tetrapods. Palaeozoic tetrapods show significant
      decreases in rates of character change whether the rate is measured per sampled
      cladistic branch or per million years along phylogeny. Given changes per branch,
      rates decrease significantly from the Devonian through the Pennsylvanian, but not
      from the Pennsylvanian through the Permian. Given changes per million years,
      rates decrease significantly over each boundary, although the decrease is least
      significant over the Pennsylvanian-Permian boundary. Decreasing rates per million
      years through the Permian might be an artefact of the method being able to
      ascribe longer durations to Permian branches than to Carboniferous ones; however,
      it is difficult to ascribe the general pattern of decreasing rates of change over
      time to sampling biases or methodological biases. Thus, the results implicate
      biological explanations for this pattern.

PMID- 16901827
TI  - The emerging diversity of Rickettsia.
AB  - The best-known members of the bacterial genus Rickettsia are associates of blood
      feeding arthropods that are pathogenic when transmitted to vertebrates. These
      species include the agents of acute human disease such as typhus and Rocky
      Mountain spotted fever. However, many other Rickettsia have been uncovered in
      recent surveys of bacteria associated with arthropods and other invertebrates;
      the hosts of these bacteria have no relationship with vertebrates. It is
      therefore perhaps more appropriate to consider Rickettsia as symbionts that are
      transmitted vertically in invertebrates, and secondarily as pathogens of
      vertebrates. In this review, we highlight the emerging diversity of Rickettsia
      species that are not associated with vertebrate pathogenicity. Phylogenetic
      analysis suggests multiple transitions between symbionts that are transmitted
      strictly vertically and those that exhibit mixed (horizontal and vertical)
      transmission. Rickettsia may thus be an excellent model system in which to study
      the evolution of transmission pathways. We also focus on the emergence of
      Rickettsia as a diverse reproductive manipulator of arthropods, similar to the
      closely related Wolbachia, including strains associated with male-killing,
      parthenogenesis, and effects on fertility. We emphasize some outstanding
      questions and potential research directions, and suggest ways in which the study
      of non-pathogenic Rickettsia can advance our understanding of their disease
      causing relatives.

PMID- 16901829
TI  - Evolutionary patterns in early tetrapods. II. Differing constraints on available
      character space among clades.
AB  - Radiations of large clades often accompany rapid morphological diversification.
      Evolutionary biologists debate the impact of external restrictions imposed by
      ecology, and intrinsic constraints imposed by development and genetics, on the
      rate at which morphological innovations are gained. These issues are particularly
      interesting for groups such as tetrapods, which evolved novel body plans relative
      to their piscine ancestors and which also invaded new ecosystems following
      terrestrialization. Prior studies have addressed these issues by looking at
      either ranges of morphological variation or rates of character change. Here, we
      address a related but distinct issue: the numbers of characters that freely vary
      within a clade. We modify techniques similar to those used by ecologists to infer
      species richnesses to estimate the number of potentially varying characters given
      the distributions of changes implied by a model phylogeny. Our results suggest
      both increasing constraints/restrictions and episodes of 'character release'
      (i.e. increasing the number of potentially varying characters). In particular, we
      show that stem lissamphibians had a restricted character space relative to that
      of stem amniotes, and that stem amniotes both had restrictions on some parts of
      character space but also invaded new character space that had been unavailable to
      stem tetrapods.

PMID- 16901830
TI  - The origin, current diversity and future conservation of the modern lion
      (Panthera leo).
AB  - Understanding the phylogeographic processes affecting endangered species is
      crucial both to interpreting their evolutionary history and to the establishment
      of conservation strategies. Lions provide a key opportunity to explore such
      processes; however, a lack of genetic diversity and shortage of suitable samples
      has until now hindered such investigation. We used mitochondrial control region
      DNA (mtDNA) sequences to investigate the phylogeographic history of modern lions,
      using samples from across their entire range. We find the sub-Saharan African
      lions are basal among modern lions, supporting a single African origin model of
      modern lion evolution, equivalent to the 'recent African origin' model of modern
      human evolution. We also find the greatest variety of mtDNA haplotypes in the
      centre of Africa, which may be due to the distribution of physical barriers and
      continental-scale habitat changes caused by Pleistocene glacial oscillations. Our
      results suggest that the modern lion may currently consist of three geographic
      populations on the basis of their recent evolutionary history: North African
      Asian, southern African and middle African. Future conservation strategies should
      take these evolutionary subdivisions into consideration.

PMID- 16901831
TI  - Human impacts and the global distribution of extinction risk.
AB  - Understanding the global geographical distribution of extinction risk is a key
      challenge in conservation biology. It remains controversial, however, to what
      extent areas become threat hotspots simply because of high human impacts or due
      to predisposing ecological conditions. Limits to the taxonomic and geographical
      extent, resolution and quality of previously available data have precluded a full
      global assessment of the relative roles of these factors. Here, we use a new
      global database on the geographical distributions of birds on continents and
      continental islands to show that, after controlling for species richness, the
      best predictors of the global pattern of extinction risk are measures of human
      impact. Ecological gradients are of secondary importance at a global scale. The
      converse is true for individual biogeographic realms, within which variation in
      human impact is reduced and its influence on extinction risk globally is
      therefore underestimated. These results underline the importance of a global
      perspective on the mechanisms driving spatial patterns of extinction risk, and
      the key role of anthropogenic factors in driving the current extinction crisis.

PMID- 16901832
TI  - A basal ceratopsian with transitional features from the Late Jurassic of
      northwestern China.
AB  - Although the Ceratopsia and Pachycephalosauria, two major ornithischian groups,
      are united as the Marginocephalia, few synapomorphies have been identified due to
      their highly specialized body-plans. Several studies have linked the
      Heterodontosauridae with either the Ceratopsia or Marginocephalia, but evidence
      for these relationships is weak, leading most recent studies to consider the
      Heterodontosauridae as the basal member of another major ornithischian radiation,
      the Ornithopoda. Here, we report on a new basal ceratopsian dinosaur, Yinlong
      downsi gen. et. sp. nov. from the Late Jurassic upper part of the Shishugou
      Formation of Xinjiang, China. This new ceratopsian displays a series of features
      transitional between more derived ceratopsians and other ornithischians, shares
      numerous derived similarities with both the heterodontosaurids and
      pachycephalosaurians and provides strong evidence supporting a monophyletic
      Marginocephalia and its close relationship to the Heterodontosauridae. Character
      distributions along the marginocephalian lineage reveal that, compared to the
      bipedal Pachycephalosauria, which retained a primitive post-cranial body-plan,
      the dominantly quadrupedal ceratopsians lost many marginocephalian features and
      evolved their own characters early in their evolution.

PMID- 16901833
TI  - Disruptive coloration, crypsis and edge detection in early visual processing.
AB  - Many animals use concealing markings to reduce the risk of predation. These
      include background pattern matching (crypsis), where the coloration matches a
      random sample of the background and disruptive patterns, whose effectiveness has
      been hypothesized to lie in breaking up the body into a series of apparently
      unrelated objects. We have previously established the effectiveness of disruptive
      coloration against avian predators, using artificial moth-like stimuli with
      colours designed to match natural backgrounds as perceived by birds. Here, we
      investigate the mechanism by which disruptive patterns reduce detectability,
      using a computational vision model of edge detection applied to photographs of
      our experimental stimuli, calibrated for bird colour vision. We show that,
      disruptive coloration is effective by exploiting edge detection algorithms that
      we use to model early visual processing. Thus, 'false' edges are detected within
      the body rather than at its periphery, so inhibiting successful detection of the
      animal's body outline.

PMID- 16901834
TI  - The distribution of species diversity across a flora's component lineages: dating
      the Cape's 'relicts'.
AB  - The Cape Floristic Region is exceptionally species-rich both for its area and
      latitude, and this diversity is highly unevenly distributed among genera. The
      modern flora is hypothesized to result largely from recent (post-Oligocene)
      speciation, and it has long been speculated that particular species-poor lineages
      pre-date this burst of speciation. Here, we employ molecular phylogenetic data in
      combination with fossil calibrations to estimate the minimum duration of Cape
      occupation by 14 unrelated putative relicts. Estimates vary widely between
      lineages (7-101 Myr ago), and when compared with the estimated timing of onset of
      the modern flora's radiation, it is clear that many, but possibly not all, of
      these lineages pre-date its establishment. Statistical comparisons of diversities
      with lineage age show that low species diversity of many of the putative relicts
      results from a lower rate of diversification than in dated Cape radiations. In
      other putative relicts, however, we cannot reject the possibility that they
      diversify at the same underlying rate as the radiations, but have been present in
      the Cape for insufficient time to accumulate higher diversity. Although the
      extremes in diversity of currently dated Cape lineages fall outside expectations
      under a constant underlying diversification rate, sampling of all Cape lineages
      would be required to reject this null hypothesis.

PMID- 16901835
TI  - Resolving multisensory conflict: a strategy for balancing the costs and benefits
      of audio-visual integration.
AB  - In order to maintain a coherent, unified percept of the external environment, the
      brain must continuously combine information encoded by our different sensory
      systems. Contemporary models suggest that multisensory integration produces a
      weighted average of sensory estimates, where the contribution of each system to
      the ultimate multisensory percept is governed by the relative reliability of the
      information it provides (maximum-likelihood estimation). In the present study, we
      investigate interactions between auditory and visual rate perception, where
      observers are required to make judgments in one modality while ignoring
      conflicting rate information presented in the other. We show a gradual transition
      between partial cue integration and complete cue segregation with increasing
      inter-modal discrepancy that is inconsistent with mandatory implementation of
      maximum-likelihood estimation. To explain these findings, we implement a simple
      Bayesian model of integration that is also able to predict observer performance
      with novel stimuli. The model assumes that the brain takes into account prior
      knowledge about the correspondence between auditory and visual rate signals, when
      determining the degree of integration to implement. This provides a strategy for
      balancing the benefits accrued by integrating sensory estimates arising from a
      common source, against the costs of conflating information relating to
      independent objects or events.

PMID- 16901836
TI  - Reading men's faces: women's mate attractiveness judgments track men's
      testosterone and interest in infants.
AB  - This study investigated whether women track possible cues of paternal and genetic
      quality in men's faces and then map perception of those cues onto mate
      attractiveness judgments. Men's testosterone concentrations served as a proxy for
      genetic quality given evidence that this hormone signals immunocompetence, and
      men's scores on an interest in infants test were chosen as prima facie markers of
      paternal quality. Women's perceptions of facial photographs of these men were in
      fact sensitive to these two variables: men's scores on the interest in infants
      test significantly predicted women's ratings of the photos for how much the men
      like children, and men's testosterone concentrations significantly predicted
      women's ratings of the men's faces for masculinity. Furthermore, men's actual and
      perceived affinity for children predicted women's long-term mate attractiveness
      judgments, while men's testosterone and perceived masculinity predicted women's
      short-term mate attractiveness judgments. These results suggest that women can
      detect facial cues of men's hormone concentrations and affinity for children, and
      that women use perception of these cues to form mate attractiveness judgments.

PMID- 16901837
TI  - Vertical jumping performance of bonobo (Pan paniscus) suggests superior muscle
      properties.
AB  - Vertical jumping was used to assess muscle mechanical output in bonobos and
      comparisons were drawn to human jumping. Jump height, defined as the vertical
      displacement of the body centre of mass during the airborne phase, was determined
      for three bonobos of varying age and sex. All bonobos reached jump heights above
      0.7 m, which greatly exceeds typical human maximal performance (0.3-0.4m). Jumps
      by one male bonobo (34 kg) and one human male (61.5 kg) were analysed using an
      inverse dynamics approach. Despite the difference in size, the mechanical output
      delivered by the bonobo and the human jumper during the push-off was similar:
      about 450 J, with a peak power output close to 3000 W. In the bonobo, most of the
      mechanical output was generated at the hips. To account for the mechanical
      output, the muscles actuating the bonobo's hips (directly and indirectly) must
      deliver muscle-mass-specific power and work output of 615 Wkg-1 and 92 Jkg-1,
      respectively. This was twice the output expected on the basis of muscle mass
      specific work and power in other jumping animals but seems physiologically
      possible. We suggest that the difference is due to a higher specific force (force
      per unit of cross-sectional area) in the bonobo.

PMID- 16901838
TI  - Disparate maturation adaptations to size-dependent mortality.
AB  - Body size is an important determinant of resource use, fecundity and mortality
      risk. Evolution of maturation size in response to size-dependent selection is
      thus a fundamental part of life-history theory. Increased mortality among small
      individuals has previously been predicted to cause larger maturation size,
      whereas increased mortality among large individuals is expected to have the
      opposite effect. Here we use a continuously size-structured model to demonstrate
      that, contrary to these widespread expectations, increased mortality among small
      individuals can have three alternative effects: maturation size may increase,
      decrease or become evolutionarily bistable. We show that such complex responses
      must be reckoned with whenever mortality is size-dependent, growth is
      indeterminate, reproduction impairs growth and fecundity increases with size.
      Predicting adaptive responses to altered size-dependent mortality is thus
      inherently difficult, since, as demonstrated here, such mortality cannot only
      reverse the direction of adaptation, but also cause abrupt shifts in
      evolutionarily stable maturation sizes.

PMID- 16901839
TI  - Dynamics of recurrent viral infection.
AB  - In chronic viral infection, low levels of viral replication and infectious
      particle production are maintained over long periods, punctuated by brief bursts
      of high viral production and release. We apply well-established principles of
      modelling virus dynamics to the study of chronic viral infection, demonstrating
      that a model which incorporates the distinct contributions of cytotoxic T
      lymphocytes (CTLs) and antibodies exhibits long periods of quiescence followed by
      brief bursts of viral production. This suggests that for recurrent viral
      infections, no special mechanism or exogenous trigger is necessary to provoke an
      episode of reactivation; rather, the system may naturally cycle through recurrent
      episodes at intervals which can be many years long. We also find that exogenous
      factors which cause small fluctuations in the natural course of the infection can
      trigger a recurrent episode. Our model predicts that longer periods between
      recurrences are associated with more severe viral episodes. Four factors move the
      system towards less frequent, more severe episodes: decreased viral infectivity,
      decreased CTL efficacy, decreased memory T cell response and increased antibody
      efficacy.

PMID- 16901840
TI  - Crossing the impassable: genetic connections in 20 reef fishes across the eastern
      Pacific barrier.
AB  - The 'impassable' Eastern Pacific Barrier (EPB), ca 5000 km of deep water
      separating the eastern from the central Pacific, is the World's widest marine
      biogeographic barrier. Sequencing of mitochondrial DNA in 20 reef fish
      morphospecies encountered on both sides of the barrier revealed cryptic
      speciation in two. Among the other 18 species only two showed significant
      differentiation (as revealed by haplotype networks and FST statistics) between
      the eastern and the central Pacific. Coalescence analyses indicated that genetic
      similarity in the 18 truly transpacific species resulted from different
      combinations of ages of most recent invasion and of levels of recurrent gene
      flow, with estimated times of initial separation ranging from approximately 30000
      to 1 Myr (ago). There is no suggestion of simultaneous interruptions of gene flow
      among the species. Migration across the EPB was previously thought to be
      exclusively eastward, but our evidence showed two invasions from east to west and
      eight cases in which subsequent gene flow possibly proceeded in the same
      direction. Thus, the EPB is sporadically permeable to propagules originating on
      either side.

PMID- 16901841
TI  - Adaptive radiation and hybridization in Wallace's Dreamponds: evidence from
      sailfin silversides in the Malili Lakes of Sulawesi.
AB  - Adaptive radiations are extremely useful to understand factors driving
      speciation. A challenge in speciation research is to distinguish forces creating
      novelties and those relevant to divergence and adaptation. Recently,
      hybridization has regained major interest as a potential force leading to
      functional novelty and to the genesis of new species. Here, we show that
      introgressive hybridization is a prominent phenomenon in the radiation of sailfin
      silversides (Teleostei: Atheriniformes: Telmatherinidae) inhabiting the ancient
      Malili Lakes of Sulawesi, correlating conspicuously with patterns of increased
      diversity. We found the most diverse lacustrine species-group of the radiation to
      be heavily introgressed by genotypes originating from streams of the lake system,
      an effect that has masked the primary phylogenetic pattern of the flock. We
      conclude that hybridization could have acted as a key factor in the generation of
      the flock's spectacular diversity. To our knowledge, this is the first empirical
      evidence for massive reticulate evolution within a complex animal radiation.

PMID- 16901842
TI  - Pheromone-sensitive glomeruli in the primary olfactory centre of ants.
AB  - Tremendous evolutional success and the ecological dominance of social insects,
      including ants, termites and social bees, are due to their efficient social
      organizations and their underlying communication systems. Functional division
      into reproductive and sterile castes, cooperation in defending the nest, rearing
      the young and gathering food are all regulated by communication by means of
      various kinds of pheromones. No brain structures specifically involved in the
      processing of non-sexual pheromone have been physiologically identified in any
      social insects. By use of intracellular recording and staining techniques, we
      studied responses of projection neurons of the antennal lobe (primary olfactory
      centre) of ants to alarm pheromone, which plays predominant roles in colony
      defence. Among 23 alarm pheromone-sensitive projection neurons recorded and
      stained in this study, eight were uniglomerular projection neurons with dendrites
      in one glomerulus, a structural unit of the antennal lobe, and the remaining 15
      were multiglomerular projection neurons with dendrites in multiple glomeruli.
      Notably, all alarm pheromone-sensitive uniglomerular projection neurons had
      dendrites in one of five 'alarm pheromone-sensitive (AS)' glomeruli that form a
      cluster in the dorsalmost part of the antennal lobe. All alarm pheromone
      sensitive multiglomerular projection neurons had dendrites in some of the AS
      glomeruli as well as in glomeruli in the anterodorsal area of the antennal lobe.
      The results suggest that components of alarm pheromone are processed in a
      specific cluster of glomeruli in the antennal lobe of ants.

PMID- 16901843
TI  - Older parents are less responsive to a stressor in a long-lived seabird: a
      mechanism for increased reproductive performance with age?
AB  - In many taxa, reproductive performance increases throughout the lifespan and this
      may occur in part because older adults invest more in reproduction. The
      mechanisms that facilitate an increase in reproductive performance with age,
      however, are poorly understood. In response to stressors, vertebrates release
      glucocorticoids, which enhance survival but concurrently shift investment away
      from reproduction. Consequently, when the value of current reproduction is high
      relative to the value of future reproduction and survival, as it is in older
      adults, life history theory predicts that the stress response should be
      suppressed. In this study, we tested the hypothesis that older parents would
      respond less strongly to a stressor in a natural, breeding population of common
      terns (Sterna hirundo). Common terns are long-lived seabirds and reproductive
      performance is known to increase throughout the lifespan of this species. As
      predicted, the maximum level of glucocorticoids released in response to handling
      stress decreased significantly with age. We suggest that suppression of the
      stress response may be an important physiological mechanism that facilitates an
      increase in reproductive performance with age.

PMID- 16901844
TI  - Cheating can stabilize cooperation in mutualisms.
AB  - Mutualisms present a challenge for evolutionary theory. How is cooperation
      maintained in the face of selection for selfishness and cheating? Both theory and
      data suggest that partner choice, where one species preferentially directs aid to
      the more cooperative members of the other species, is central to cooperation in
      many mutualisms. However, the theory has only so far considered the evolutionary
      effects of partner choice on one of the species in a mutualism in isolation.
      Here, we investigate the co-evolution of cooperation and choice in a choosy host
      and its symbiont. Our model reveals that even though choice and cooperation may
      be initially selected, it will often be unstable. This is because choice reduces
      variation in the symbiont and, therefore, tends to remove the selective incentive
      for its own maintenance (a scenario paralleled in the lek paradox in female
      choice and policing in within-species cooperation). However, we also show that
      when variability is reintroduced into symbionts each generation, in the form of
      less cooperative individuals, choice is maintained. This suggests that the
      presence of cheaters and cheater species in many mutualisms is central to the
      maintenance of partner choice and, paradoxically, cooperation itself.

PMID- 16901845
TI  - Differences in cue use and spatial memory in men and women.
AB  - Men and women differ in their ability to solve spatial problems. There are two
      possible proximate explanations for this: (i) men and women differ in the kind
      (and value) of information they use and/or (ii) their cognitive abilities differ
      with respect to spatial problems. Using a simple computerized task which could be
      solved either by choosing an object based on what it looked like, or by its
      location, we found that the women relied on the object's visual features to solve
      the task, while the men used both visual and location information. There were no
      differences between the sexes in memory for the visual features of the objects,
      but women were poorer than men at remembering the locations of objects.

PMID- 16901846
TI  - Evolutionary games on cycles.
AB  - Traditional evolutionary game theory explores frequency-dependent selection in
      well-mixed populations without spatial or stochastic effects. But recently there
      has been much interest in studying the evolutionary game dynamics in spatial
      settings, on lattices and other graphs. Here, we present an analytic approach for
      the stochastic evolutionary game dynamics on the simplest possible graph, the
      cycle. For three different update rules, called 'birth-death' (BD), 'death-birth'
      (DB) and 'imitation' (IM), we derive exact conditions for natural selection to
      favour one strategy over another. As specific examples, we consider a
      coordination game and Prisoner's Dilemma. In the latter case, selection can
      favour cooperators over defectors for DB and IM updating. We also study the case
      where the replacement graph of evolutionary updating remains a cycle, but the
      interaction graph for playing the game is a complete graph. In this setting, all
      three update rules lead to identical conditions in the limit of weak selection,
      where we find the '1/3-law' of well-mixed populations.

PMID- 16901847
TI  - Consequences of low birthweight on urinary excretion of DNA markers of oxidative
      stress in young men.
AB  - OBJECTIVE: Low birthweight (LBW) has been associated with an increased risk of
      development of type 2 diabetes in adult life. Both type 1 and type 2 diabetes
      mellitus are characterized by increased oxidative stress. The purpose of this
      study was to investigate whether young healthy adults born with LBW showed
      differences in oxidative stress under normal conditions and during the added
      challenge of a physiological Intralipid infusion. MATERIAL AND METHODS: Urinary
      excretion of DNA markers of oxidative stress were analyzed by LC-MS/MS in 19 men
      (aged 19 years) with LBW and in 19 age matched, normal birthweight (NBW) controls
      pre- and post a 3-fold increase of plasma free fatty acids. RESULTS: Mean
      excretion rates of 8-oxo-guanine (8oxoGua), 8-oxo-guanosine (8oxoGuo), 8-oxo
      2'deoxyguanosine (8oxodG), and 1,N6-ethenodeoxyadenosine (epsilon dA) did not
      statistically differ between subjects with LBW and NBW (66.9 versus 73.9 nmol/15
      h, 17.8 versus 18.5 nmol/15 h, 11.9 versus 14.4 nmol/15 h and 44.0 versus 43.2
      pmol/15 h, respectively). Furthermore, Intralipid infusion did not affect
      excretion of DNA adducts in LBW or NBW subjects. Statistically significant
      correlations were found between body mass index and urinary excretion of 8oxoGua
      (r = 0.64, p = 0.003) and 8oxoGuo (r = 0.64, p = 0.003) in the LBW group only.
      CONCLUSIONS: These findings suggest that oxidative stress may be a consequence of
      diabetes and is not, or at least only partly, involved in the early pathogenesis
      of type 2 diabetes.

PMID- 16901849
TI  - Pulse-wave morphology and pulse-wave velocity in healthy human volunteers:
      examination conditions.
AB  - OBJECTIVE: Applanation tonometry for pulse-wave analysis (PWA) and determination
      of pulse-wave velocity (PWV) is a non-invasive method for assessment of the
      central aortic pressure waveform and indices of arterial stiffness. The objective
      of this study was to examine the influence of eating and smoking on PWA and PWV
      measurements in order to establish standard examination conditions. Furthermore,
      intra- and interobserver reproducibility and the effects of varying the site of
      measurements were observed. MATERIAL AND METHODS: Duplicate measurements of the
      radial pressure waveform and of the brachial and aortic PWV on the right and left
      side of the body were recorded in 23 healthy subjects by two trained observers.
      Measurements were performed in the fasting state and 3 h after a high-calorie
      meal, and before and 1 h after smoking a cigarette. RESULTS: Intake of a high
      calorie meal as well as smoking caused significant changes in both PWA and PWV
      parameters and an inter-arm difference was observed. Intra- and interobserver
      reproducibility was good. CONCLUSIONS: Pulse-wave measurements by applanation
      tonometry should be undertaken in the same arm during fasting and smoking
      abstinence.

PMID- 16901848
TI  - Relation of myeloperoxidase promoter polymorphism and long-term hormone
      replacement therapy to oxidized low-density lipoprotein autoantibodies in
      postmenopausal women.
AB  - OBJECTIVE: The myeloperoxidase enzyme (MPO) is a potent precursor of low-density
      lipoprotein (LDL) oxidation in atherosclerotic lesions. The MPO gene has a
      promoter polymorphism, 463G/A, which leads to high (GG) and low-expression (AG,
      AA) genotypes. Hormone replacement therapy (HRT) is known to affect MPO activity
      and LDL oxidation. The purpose of this study was to test whether the effect of
      HRT on the levels of oxLDL-ab varies according to MPO genotype. MATERIAL AND
      METHODS: Eighty-seven postmenopausal women aged 45-71 years were divided into
      three groups based on the use of HRT. The HRT-EVP group (n = 25) used sequential
      estradiol valerate (EV) plus progestin, the HRT-EV group (n = 32) used EV alone,
      and the control group (n = 30) no HRT. MPO genotypes were determined by
      polymerase chain reaction (PCR) and oxLDL-ab by ELISA. RESULTS: We found a
      significant HRT group by MPO genotype interaction (p = 0.021) in plasma oxLDL-ab
      levels. In subjects with the GG genotype, the oxLDL-ab titer increased in the
      order of 2.13 in controls, 2.53 in the EV group and 3.21 in the EVP group (ANOVA
      for trend p = 0.006). CONCLUSIONS: The effects of HRT on LDL oxidation can vary
      according to MPO genotype and the concurrent progestin therapy with EV may
      counteract the more neutral effect of EV on LDL oxidation in subjects with the
      MPO high-expression genotype.

PMID- 16901850
TI  - Serotonin and superior mesenteric artery resistance index.
AB  - OBJECTIVE: Serotonin is a vasoactive neuroendocrine substance and serotonergic
      drugs are promising agents for the treatment of functional gastrointestinal
      disorders. The effect of serotonin on superior mesenteric blood flow in humans is
      unknown. The aim of this study was to examine the effect of exogenous serotonin
      on superior mesenteric artery blood flow, as estimated by the resistance index
      with Doppler ultrasound, in healthy human volunteers. MATERIAL AND METHODS: Six
      fasting healthy adult volunteers of both genders were studied. Transabdominal
      Doppler ultrasound was used to evaluate the effects of either a standard meal or
      intravenous infusion of serotonin (2.5-20 nmol kg-1 min-1) on the superior
      mesenteric artery resistance index, platelet-depleted plasma levels of serotonin,
      blood pressure, heart rate and electrocardiogram. RESULTS: All subjects had the
      same patterns of response to meal and serotonin stimulation. Meal stimulation
      decreased the mean resistance index from 0.84+/-0.04 to 0.72+/-0.02 (p = 0.0004)
      and increased platelet-depleted-plasma levels of serotonin from 50+/-36 to 61+/
      46 nmol L-1 (p = 0.04). Serotonin stimulation increased the mean resistance index
      from 0.82+/-0.04 to 0.88+/-0.03 (p = 0.006) and mean platelet-depleted-plasma
      levels of serotonin from 44+/-24 to 83+/-37 nmol L-1 (p = 0.03). Most subjects
      reported minor short-lived adverse effects. Electrocardiogram results were
      unchanged during all examinations. CONCLUSIONS: We conclude that intravenous
      infusion of serotonin increases the resistance index of the superior mesenteric
      artery (increases downstream resistance) in healthy adult volunteers.

PMID- 16901851
TI  - In vivo veritas: thrombosis mechanisms in animal models.
AB  - Experimental models have enhanced our understanding of atherothrombosis
      pathophysiology and have played a major role in the search for adequate
      therapeutic interventions. Various animal models have been developed to simulate
      thrombosis and to study in vivo parameters related to hemodynamics and rheology
      that lead to thrombogenesis. Although no model completely mimics the human
      condition, much can be learned from existing models about specific biologic
      processes in disease causation and therapeutic intervention. In general, large
      animals such as pigs and monkeys have been better suited to study atherosclerosis
      and arterial and venous thrombosis than smaller species such as rats, rabbits,
      and dogs. On the other hand, mouse models of arterial and venous thrombosis have
      attracted increasing interest over the past two decades, owing to direct
      availability of a growing number of genetically modified mice, improved technical
      feasibility, standardization of new models of local thrombosis, and low
      maintenance costs. To simulate rupture of an atherosclerotic plaque, models of
      arterial thrombosis often involve vascular injury, which can be achieved by
      several means. There is no animal model that is sufficiently tall, that can mimic
      the ability of humans to walk upright, and that possesses the calf muscle pump
      that plays an important role in human venous hemodynamics. A number of
      spontaneous or genetically engineered animals with overexpression or deletion of
      various elements in the coagulation, platelet, and fibrinolysis pathways are now
      available. These animal models can replicate important aspects of thrombosis in
      humans, and provide a valuable resource in the development of novel concepts of
      disease mechanisms in human patients.

PMID- 16901852
TI  - Enhanced detection rate of typhoid fever in children in a periurban slum in
      Karachi, Pakistan using polymerase chain reaction technology.
AB  - OBJECTIVE: Yield of blood culture in clinically suspected cases of typhoid fever
      is low, whereas indirect serological diagnostic tests are unreliable. Hence,
      polymerase chain reaction (PCR)-based detection of Salmonella enterica Serovar
      typhi was used as an aid for diagnosis of typhoid fever in addition to other
      diagnostic tests. Two periurban communities in Karachi were selected for an
      epidemiological study of typhoid fever. The aim of the study was to assess
      whether PCR increased the detection rate of typhoid fever in children in the
      community. MATERIAL AND METHODS: Children aged 2 to 14 years presenting with
      fever lasting for three or more days were selected. PCR using Hashimoto's
      protocol based on ViaB gene sequence was used in addition to blood culture and
      other serological tests. RESULTS: Of the 214 children included in the study,
      blood culture was found positive for S. enterica S. typhi in 26 (12.4%) cases,
      whereas 24 children (11.7%) were diagnosed as suffering from typhoid fever when
      the PCR-based method was used. Both tests were positive in only 10 (4.9%)
      children. The number of children found positive for either test was 40. PCR
      increased the rate of detection of typhoid fever by 51%. CONCLUSION: The
      sensitivity, specificity, +ve and -ve predictive values of PCR in this study were
      40%, 93%, 45% and 92%, respectively.

PMID- 16901853
TI  - Albuminuria, intermittent hyperfiltration and salt wasting in patients with
      stroke: a pilot study.
AB  - OBJECTIVE: To investigate whether different types of stroke influence renal
      excretion of albumin, major electrolytes and water. MATERIAL AND METHODS: Timed
      urine collections were started shortly after admission in 5 patients with
      haemorrhagic stroke (group A), 5 with ischaemic stroke (group Bx), 6 with
      presumed ischaemic stroke (groups By/z) and 6 with subarachnoid haemorrhage
      (group C). Albuminuria was also investigated in four patients undergoing elective
      abdominal surgery. RESULTS: Increased levels of albuminuria were observed in all
      patients in groups A and B, but were found to decline with observation time and
      appeared to be related to outcome in group B. In group C, albuminuria was
      detected in 4 out of 6 patients. Elective surgery did not affect albumin
      excretion. In a setting with high urinary osmolality, high excretion rates for
      creatinine, urea, sodium, potassium and large diuresis were intermittently
      observed in groups A, B and C. None of these patients was in steady-state
      condition. CONCLUSIONS: Different types of stroke elicit a complex change in
      renal function which resembles the response to a hypervolaemic and hyperosmolar
      signal, possibly mediated by a breakdown of renal autoregulation of blood flow in
      the presence of high vasopressin activity. Acute changes in excretion of albumin
      might be an indicator of prognosis in stroke. The findings point to the existence
      of unrecognized pathways between the central nervous system and the kidneys.
      Further studies on the mechanisms underlying alterations in renal function in
      stroke and their implication for treatment and outcome are indicated.

PMID- 16901855
TI  - Structural identification of a new acetildenafil analogue from pre-mixed bulk
      powder intended as a dietary supplement.
AB  - An analogue of acetildenafil was detected in an extract of pre-mixed bulk powder.
      To our knowledge, the powder was destined to be encapsulated and sold as a
      dietary supplement. The structure was identified by NMR, HR-ESI-MS, ESI-MSn and
      FTIR analyses. Owing to the inclusion of a hydroxyl group in acetildenafil, the
      detected compound was called 'hydroxyacetildenafil'. With increasing use of
      dietary supplements marketed for penile erectile dysfunction, the detection of
      analogues of sexual performance enhancers is important and timely.

PMID- 16901854
TI  - Generation of an antibody specific to erythritol, a non-immunogenic food
      additive.
AB  - Erythritol, a simple sugar alcohol, is widely used as a food and drug additive
      owing to its chemical inertness, sweetness and non-toxicity. Adverse reactions to
      erythritol are rare and only three cases of allergic reactions to foods
      containing erythritol have been reported. Being inert, erythritol cannot produce
      an immunological response. In order to explain the mechanism of immunogenicity of
      erythritol, a method to obtain erythritol epitopes on a carrier protein, which
      can serve as an immunogen to develop antibodies against erythritol, is described.
      D-Erythrose was conjugated to bovine serum albumin at pH 8 by reductive
      amination. The reduction product of the Schiff base of D-erythrose-bovine serum
      albumin conjugate creates erythritoyl groups. Rabbits immunized with erythritol
      bovine serum albumin conjugate (29 haptens/molecule) showed good antibody
      response (detection of 1 microg antigen, erythritol-keyhole limpet haemocyanin
      conjugate possessing 50% modified amino groups, at 1 : 50,000 dilution). Anti
      erythritol immunoglobulin-G antibodies were purified from the immune serum using
      hapten-affinity chromatography on an erythritol-keyhole limpet haemocyanin
      Sepharose CL-6B affinity matrix. The yield of erythritol-specific antibody was
      approximately 40 microg ml-1 of rabbit antiserum. Enzyme-linked immunobsorbant
      assay inhibition studies using sugars, sugar alcohols and L-lysine showed minimal
      cross-reactivity (approximately 4%) when compared with erythritol; only
      dithioerythritol showed a cross-reactivity of approximately 33%. D-Threitol and L
      threitol (isomers of erythritol) had cross-reactivities of 15 and 11%,
      respectively. The inhibition studies confirmed the haptenic nature of erythritol
      and indicated that the erythritoyl group is a single epitope. The reaction scheme
      outlined here for the generation of erythritol epitopes appears to provide a
      basis for the immunogenicity of erythritol.

PMID- 16901856
TI  - Development of an innovative immunoassay for CP4EPSPS and Cry1AB genetically
      modified protein detection and quantification.
AB  - An innovative immunoassay, called enzyme-linked immunoabsorbant assay (ELISA)
      Reverse, based on a new conformation of the solid phase, was developed. The solid
      support was expressly designed to be immersed directly in liquid samples to
      detect the presence of protein targets. Its application is proposed in those
      cases where a large number of samples have to be screened simultaneously or when
      the simultaneous detection of different proteins is required. As a first
      application, a quantitative immunoassay for Cry1AB protein in genetically
      modified maize was optimized. The method was tested using genetically modified
      organism concentrations from 0.1 to 2.0%. The limit of detection and limit of
      quantitation of the method were determined as 0.0056 and 0.0168 (expressed as the
      percentage of genetically modified organisms content), respectively. A
      qualitative multiplex assay to assess the presence of two genetically modified
      proteins simultaneously was also established for the case of the Cry1AB and the
      CP4EPSPS (5-enolpyruvylshikimate-3-phosphate synthase) present in genetically
      modified maize and soy, respectively.

PMID- 16901857
TI  - Dietary intake of toxic and essential trace elements by the children and parents
      living in Tokyo Metropolitan Area, Japan.
AB  - This study estimated the dietary intakes of 25 pairs of Japanese children and
      their parents to 12 toxic and essential trace elements using 7-day duplicate diet
      composites. The estimated intakes of lead (children = 5.34 microg day-1, adults =
      6.74 microg day-1) and tin (162 and 152 microg day-1) were below tolerable
      limits, but large difference in aluminium intakes (7.32 and 12.1 mg day-1) among
      the subjects warranted further investigations. Intakes of cadmium in both
      children and adults (13.2 and 15.9 microg day-1) were high, but a low uranium (U)
      intake was observed (0.593 and 0.587 microg day-1). Intakes of copper (567 and
      784 microg day-1), manganese (1.56 and 2.72 mg day-1), zinc (4.93 and 6.75 mg day
      1), and molybdenum (103 and 131 microg day-1) were close to the recommended
      values. Concentrations of chromium, nickel and selenium were lower than the
      detection limits in most cases.

PMID- 16901858
TI  - Effects of processing on pesticide residues in peaches intended for baby food.
AB  - Peaches containing added residues of chlorpyrifos-methyl, fenitrothion,
      procymidone and vinclozolin were used for simulated industrial processing in the
      manufacture of baby food puree. Residues were determined in raw material, in
      intermediate products at crucial steps of the processing procedure and in final
      products. Determination of residues was performed by an analytical method,
      distinguished by high sensitivity, based on acetone extraction, a two-step clean
      up/pre-concentration on graphitized carbon and SAX/PSA sorbent, and GC-ECD. The
      results of the study were interpreted with respect to enforcement of the
      stringent Maximum Residue Limit (MRL) of 0.01 mg kg-1 established by the European
      Commission (EC) for any pesticide in baby food. Peeling was identified as the
      most effective procedure in reducing residues. Thermal treatment (concentration
      and sterilisation) substantially reduced organophosphate (chlorpyrifos-methyl,
      fenitrothion) residues, whereas procymidone and vinclozolin residue levels were
      increased in peach puree.

PMID- 16901859
TI  - Reliable indirect competitive ELISA used for a survey of ochratoxin A in green
      coffee from the North of Parana State, Brazil.
AB  - The performance of an indirect competitive enzyme-linked immunosorbent assay (ic
      ELISA) based on a monoclonal antibody (mAb) for ochratoxin A (OTA) detection was
      evaluated in a comparative study with high-performance liquid chromatography
      (HPLC) analysis using 68 freshly harvested coffee samples from the North of
      Parana State, Brazil. The anti-OTA mAb showed high specificity and low cross
      reactivity with OTA analogues (OTB and OTalpha), but cross-reacted with OTC. This
      ic-ELISA showed a detection limit of 3.75 ngg-1 sample, when compared to 0.80 ngg
      1 by HPLC, with an ic-ELISA/HPLC correlation coefficient of 0.90. As regards OTA
      analysis of these coffee samples, natural contamination was detected in 10
      samples (14.7%) by both methods, where the ic-ELISA values (range 3.9-7.3 ngg-1)
      were 1.1 to 1.6-fold higher than HPLC data (2.7-4.7 ngg-1). Five samples (7.4%)
      were OTA positive (range 0.84-1.30 ngg-1) only by HPLC assay, probably due to the
      higher detection limit reached by ic-ELISA. OTA was undetectable in 53 samples
      (77.9%) by both methods, while all positive samples (range 0.84-7.30 ngg-1)
      showed OTA levels lower than 8 ngg-1 (maximum limit recommended by the European
      Union). The matrix interference of green coffee was minimized by dilution of
      sample extracts before carrying out the ELISA assay. This mAb-based ic-ELISA can
      be effectively applied for OTA screening in coffee, because it is simple,
      sensitive and sample preparation is easy.

PMID- 16901860
TI  - Comparison of ochratoxin A and deoxynivalenol in organically and conventionally
      produced beers sold on the Belgian market.
AB  - Beer was chosen as a cereal-derived and homogeneous product for a comparison of
      organic and conventional production methods in terms of mycotoxin contamination
      levels. Ochratoxin A (OTA, a storage mycotoxin) and deoxynivalenol (DON, a field
      mycotoxin) were assessed by HPLC in organically and conventionally produced beers
      sold in Belgium. Immunoaffinity column (OchraTest and DONPrep) purification was
      used prior to HPLC analysis. For in-house validation, recovery experiments,
      carried out with the spiked beers in the ranges of 50-200 ng OTA l-1 and 20-100
      microg DON l-1, led to the overall averages of 91% (RSD = 10%, n = 9) and 93%
      (RSD = 5%, n = 27), respectively. Organic beers collected during 2003-2004 were
      more frequently OTA-contaminated (95%, n = 40) than their conventional
      counterparts (50%, n = 40). Conventional beers were OTA-contaminated at a mean
      concentration of 25 ng l-1 (range: 19-198 ng l-1), while organic beers contained
      a mean level of 182 ng l-1 (range: 18-1134 ng l-1). High OTA contamination above
      the limit of 200 ng l-1 (up to 1134 ng l-1) occasionally occurred in organically
      produced beers. A complementary survey performed with the same brands in 2005 did
      not confirm this accidental presence of excessive OTA loads (range: 3-67 ng l-1
      for 10 conventional beers and 19-158 ng l-1 for 10 organic beers). Establishing a
      maximum of 3 microg OTA kg-1 in malt, the application of the regulation EC No.
      466/2001 (entered in force before the last sampling) may be related to the
      observed improvement. The overall incidence of DON was 67 and 80% in conventional
      and organic beers, respectively. DON concentrations ranged from 2 to 22 microg
      DON l-1 (mean = 6 microg DON l-1) in conventional beers, while organic beers
      ranged from 2 to 14 microg DON l-1 (mean=4 microg DON l-1). Thus, DON in beers
      does not appear to be a major matter of concern. From the statistical tests, it
      was concluded that the variation between different batches was significant (P <
      0.0001), in contrast to that observed between different brands, showing a lack of
      homogeneity in the raw materials. This occurs either in organically or in
      conventionally produced materials. Considering these results, an optimized
      frequency of controls according to European Regulations EC No 466/2001 and EC No
      856/2005 should be recommended to reject the irregular batches.

PMID- 16901861
TI  - Assessment of dietary intake of polychlorinated biphenyls from a total diet study
      conducted in Pavia, Northern Italy.
AB  - The diet is considered to be the main source of body burden of
      polychlorobiphenyls (PCBs) in the general population. The most cost-effective and
      reliable way to estimate the dietary intake is based on total diet studies
      (TDSs). The aim of the present study was to provide a reliable estimate of recent
      average dietary intakes of PCBs in Northern Italy. Congener-specific analysis of
      PCBs was undertaken on total diet samples collected at the cafeteria of the
      University of Pavia. The average daily intake for total PCBs was calculated to be
      0.26 microg/person day-1. The major contributor to PCB intake was accounted for
      by pooled samples of bread, cereals and potatoes, followed by the protein
      composite, and fruit and vegetables. Although diverse dietary habits and
      differences in sampling and analytical procedures make comparison between
      different studies difficult, the daily intake of PCBs in Northern Italy can be
      located in the lower part of the range for values reported in the literature.

PMID- 16901862
TI  - Dioxins and polychlorinated biphenyls (PCBs) in fish oil dietary supplements:
      occurrence and human exposure in the UK.
AB  - Commercially available fish oil supplements sourced from retail outlets in the
      UK, as well as by mail order, were surveyed in 2000-02 for dioxin (PCDD/Fs) and
      polychlorinated biphenyl (PCB) content. Sampled products were representative of
      market share. The WHO-TEQ values for these products ranged from 0.18 to 8.4 ng kg
      1 for SigmaPCDD/F and from 1.1 to 41 ng kg-1 for Sigma dioxin-like PCBs. The
      results suggest a downward trend in the levels of dioxins in fish oil supplements
      over the last decade, since levels for similar products ranged from 0.3 to 10 ng
      kg-1 for SigmaPCDD/F WHO-TEQ in 1996. Levels of ICES (International Council for
      the Exploration of the Seas) 7 PCBs in the current study ranged from 8.3 to 267
      microg kg-1. Subsequent to this survey, European Union legislation has been
      introduced that includes a maximum limit of 2 ng kg-1 WHO-TEQ for dioxins in fish
      oil products for human consumption. Twelve of the 33 products reported here would
      have exceeded this limit. Negotiations are in progress to incorporate dioxin-like
      PCBs into the European Union regulations. When manufacturer-recommended doses
      were applied to the observed levels, the estimated upper bound human exposure to
      dioxins and dioxin-like PCBs from dietary intake of these products ranged from
      0.02 to 7.1 pg WHO-TEQ kg-1 body weight day-1 for adults and from 0.02 to 10 pg
      WHO-TEQ kg-1 body weight day-1 for schoolchildren. This level rises to 1.8-8.9 pg
      WHO-TEQ kg-1 body weight day-1 for adults and 1.4-14 pg WHO-TEQ kg-1 body weight
      day-1 for schoolchildren when combined with the average exposure from the whole
      diet in 1997. Again, subsequent to this survey, the Committee on Toxicity of
      Chemicals in Food, Consumer Products and the Environment (COT) revised the UK
      tolerable daily intake (TDI) for mixtures of dioxins and dioxin-like PCBs from 10
      to 2 pg WHO-TEQ kg-1 body weight day-1. This is in line with the tolerable weekly
      intake (TWI) of 14 pg WHO-TEQ kg-1 body weight set by the Scientific Committee on
      Food (SCF).

PMID- 16901863
TI  - Migration of formaldehyde and melamine monomers from kitchen- and tableware made
      of melamine plastic.
AB  - Migration of one or both formaldehyde and/or melamine monomers was found in seven
      of ten tested melamine samples bought on the Danish market. The samples were a
      bowl, a jug, a mug, a ladle, and different cups and plates. No violation of the
      European Union-specific migration limits for melamine (30 mg kg-1) and
      formaldehyde (15 mg kg-1) was found after three successive exposures to the food
      stimulant 3% acetic acid after 2 h at 70 degrees Celsius. To investigate the
      effects of long-term use, migration tests were performed with two types of cups
      from a day nursery. Furthermore, medium-term use was studied by ten successive
      exposures of a plate to 3% acetic acid for 30 min at 95 degrees Celsius. The
      results indicate that continuous migration of formaldehyde and melamine takes
      place during the lifetime of these articles. The molar ratio of released
      formaldehyde to melamine was seen to decrease from 12 to about 5. This indicates
      that, first, the migration of residual monomers is most important, but in the
      long-term, breakdown of the polymer dominates. Two CEN methods were used to
      determine the concentration of monomers: a spectrophotometric method for
      formaldehyde and a UV-HPLC method for melamine.

PMID- 16901864
TI  - "Fag church": men who integrate gay and Christian identities.
AB  - It is usually assumed that being gay or lesbian and being Christian is
      contradictory. The eight men who participated in this qualitative inquiry
      demonstrate otherwise. I investigated the ways in which these men integrated
      their gay and Christian identities meaningfully into their lives. From the
      interview data, I discerned and describe in this paper a variety of strategies
      that these men adopted in order to facilitate identity integration of seemingly
      mutually exclusive identities. In the bid for social and political equality with
      heterosexuals, gays and lesbians typically have not received support from
      Christians, at least not from politically active Christians, many of whom
      participate in explicitly antigay campaigns. Given such a contentious context, I
      discuss the personal and political implications of integrating gay and
      evangelical Christian identities.

PMID- 16901865
TI  - Stereotype or success? Prime-time television's portrayals of gay male, lesbian,
      and bisexual characters.
AB  - The current content analysis of prime-time network television during the fall of
      2001 seeks to identify the representation of Gay male, Lesbian, and Bisexual
      characters in shows known to have one reoccurring homosexual character based on
      the theories of Clark and Berry. Clark (1969) established four stages of media
      representation for minority groups: non-representation, ridicule, regulation, and
      respect. The findings of the study support the premise that Gay males and
      Lesbians have passed Clark's stage of non-representation and have progressed into
      the stage of ridicule and some are moving into the stages of regulation and
      respect. Berry (1980) devised three periods based on the television portrayal of
      Blacks: The Stereotypic Age, The New Awareness, and Stabilization. Results were
      mixed, with only a partial support of the hypothesis that Gay males and Lesbians
      had advanced beyond The Stereotypic Age.

PMID- 16901866
TI  - Explaining comfort with homosexuality in rural america.
AB  - While recent research has explored the determinants of homophobia in urban
      settings, few have looked at the perception of homosexuals in rural communities.
      This research fills this gap by exploring the ways in which Central Appalachians
      feel about homosexuality. In doing so, the impact of interpersonal contact with a
      homosexual as well as the factors of gender, age, religious beliefs, gender role
      prescriptions and fear of AIDS are identified through a multivariate analysis of
      123 college students. In the end, the role of homosexual peers is emphasized, as
      are the effects of the perceived cause of homosexuality, and the anxieties over
      AIDS. Finally after some stipulations about methodological limitations, this work
      offers some suggestions as to how practitioners and social work educators can use
      this study to counter the homophobic ideas that are prevalent in rural Americans.

PMID- 16901867
TI  - Public attitudes toward gays and lesbians: trends and predictors.
AB  - Public opinion about gay men and lesbians is a popular topic in both the popular
      press and academic journals. However, analyses of attitudinal trends are rare.
      Tracing changes in opinion polls on homosexuals in the United States between 1977
      and 2003, the first part of the present study showed that public opinion of this
      minority group has become more positive over time. Part two of this research
      utilized a recent national survey to identify factors predicting anti-gay
      attitudes. The best predictors included respondents' sex, stance of anti-abortion
      and anti-women's equality, and religiosity. Implications for gay rights advocates
      were discussed.

PMID- 16901868
TI  - Positive associations among interpersonal contact, motivation, and implicit and
      explicit attitudes toward gay men.
AB  - A correlational study explored the role of intergroup contact and motivation to
      respond without prejudice on heterosexuals' expression of explicit and implicit
      (unconscious) bias against gay men. Participants who reported having more
      relationships and closer relationships with gay, lesbian, or bisexual people
      tended to exhibit more favorable attitudes toward gay men on implicit as well as
      explicit attitude measures. Attitudes were also related to self-reported
      motivation to be non-prejudiced, including motivation stemming from sources
      internal as well as external to the individual. Multiple regression analyses
      showed that contact and motivation explain unique variance in attitude but that
      motivation is a relatively stronger predictor. The results are interpreted to
      suggest that implicit and explicit prejudice may be reduced through motivation
      coupled with positive contact experiences.

PMID- 16901869
TI  - Disclosure patterns within social networks of gay men and lesbians.
AB  - Gay men and lesbians must make decisions about disclosure of their sexual
      orientation. Past research has focused on an individual's overall level of
      disclosure or on disclosure to a specific subset of individuals. This study used
      a new measure, the Disclosure Grid, to assess the disclosure patterns of 89 gay
      men and 55 lesbians across their entire social network. In addition to assessing
      disclosure to each network member, the Grid also assessed perceived relationship
      quality prior to disclosure and currently. Finally, the Grid assessed perceptions
      of each network member's initial and current acceptance of the gay or lesbian
      person's sexual orientation. Data provide a rich portrait of disclosure patterns
      among a heterogeneous, urban sample of lesbians and gay men. Analyses also found
      support for three hypotheses about disclosure, relationship quality, and
      acceptance. For example, it was found that participants have better relationships
      with individuals they have directly told about their sexual orientation than with
      people who found out in an indirect manner.

PMID- 16901870
TI  - With friends like these. . .the role of prejudice and situational norms on
      discriminatory helping behavior.
AB  - An experiment was conducted to examine the impact of homophobic attitudes and
      situational norms for helping on discriminatory behavior against a gay male. In a
      partial replication of Frey and Gaertner (1986), participants were asked to
      provide help to a confederate portrayed to be either gay or heterosexual who
      either requested help for himself (ambiguous situational norm) or for whom a
      third party requested help (unambiguous situational norm). Participants' levels
      of homophobia were assessed either before or after the main helping task. The
      results indicated that when norms for helping were ambiguous those participants
      higher in homophobia discriminated against the gay male, but only on subtle
      indicators of discrimination. In the unambiguous norm condition, participants
      higher in homophobia discriminated against the heterosexual male. Those lower in
      homophobia did not discriminate under either norm condition. The results show
      that it may be sufficient for those with prejudiced attitudes just to believe
      that it is not "the wrong thing to do" for their attitudes to be translated into
      some form of discriminatory behavior.

PMID- 16901871
TI  - Exploring heterosexual women's anti-lesbian attitudes.
AB  - Previous research on attitudes toward gays has mostly focused on heterosexuals'
      attitudes toward gay men, with little research specifically directed at anti
      lesbian attitudes. Using a sample of 269 undergraduate heterosexual women, the
      present study tested two feminist propositions: Anti-lesbian attitudes would be
      associated with (1) conservative beliefs regarding the female gender-role and (2)
      attitudes toward men that support the differential status of women and men in the
      patriarchy. Findings based on a series of multiple regression analyses support
      these propositions across three components of anti-lesbian attitudes (contact
      apprehension, morality beliefs, and stereotypic beliefs). Directions for future
      research on anti-lesbian attitudes are discussed.

PMID- 16901874
TI  - Elderly African Americans as intragenerational caregivers.
AB  - A growing number of older Americans serve as caregiving resources for their
      elderly spouses, partners, relatives, and/or friends. Yet, little research has
      addressed the impact and implications of this trend among African Americans. This
      article describes the results of a qualitative study examining the
      intragenerational caregiving experiences and perspectives of two cohorts of
      African Americans (urban and rural, N = 129) between the ages of 58 and 89. Its
      findings reveal important differences and commonalities associated with elderly
      African American caregivers and their care giving in urban and rural settings.
      Additionally, the study suggests that volunteer caregivers can often fill the
      void left by partners and relatives who predecease or fail to assume
      responsibility for the care of their elderly relatives. Their efforts do not
      displace those of friends and family members, but rather address unmet needs in
      available care. The discussion focuses on the implications of the study findings
      for public policy and practice.

PMID- 16901875
TI  - Suicide risk assessment in the depressed elderly patient with cancer.
AB  - Although several studies have identified different factors that increase the risk
      for suicide in the elderly, depression, especially in cancer patients, puts
      people at even greater risk. In geriatric patients with co-morbid illnesses,
      depression is often diagnosed or overlooked because of the assumption that it is
      to be expected. When patients with cancer are diagnosed with depression, it is
      imperative that clinicians have a clear-cut tool for assessing and identifying
      signs of suicidality in order to develop a treatment plan to manage the patient.
      This article delineates the steps involved in conducting a thorough and
      systematic suicide risk assessment in depressed elderly patients with cancer.

PMID- 16901876
TI  - Assisting older victims of disasters: roles and responsibilities for social
      workers.
AB  - The tumultuous catastrophic tragedies of the Oklahoma bombing in 1995 and
      September 11, 2001 attacks on the World Trade Center and Pentagon have caused
      urgency for the profession of social work to be ready to respond to unexpected
      crises whether directed to an individual, group, or nation. While there has
      always been the possibility of tragedies in the U.S. caused by nature (so-called
      "acts of God") or the spontaneous or planned acts of criminals or the deranged,
      the increased awareness of catastrophes includes, as never before, disasters that
      are perpetrated by terrorist acts from within or outside of the U.S. The creation
      of the Department of Homeland Security, in 2003, underscores the need for
      awareness and for preparation on the part of the nation. Based upon its skills
      and values, social workers have significant roles to play in the face of
      potential and actual disasters; yet, gerontological social workers have
      additional responsibilities for addressing the needs of older persons. It is the
      purpose of this article to provide an overview of issues to be considered by
      social workers, in general, and gerontological social workers, in particular,
      with regard to preparation for possible disasters and the consequences from such
      catastrophes that affect older persons.

PMID- 16901877
TI  - Evaluating the Senior Companion Program: a mixed-method approach.
AB  - This article reports on a mixed-method assessment of the Senior Companion Program
      (SCP), a federal program which provides volunteer opportunities with small
      stipends to low-income older adults, 60 years of age and older, who provide
      companionship and offer assistance to frail community elders. Through four
      standardized scales and open-ended questions regarding the impact of the SCP in
      their lives, 34 Senior Companion volunteers and 32 of their clients were
      interviewed. Informants reported relatively large social networks and low levels
      of depression and loneliness. Thematic analysis of the qualitative data revealed
      the benefits of the program for both volunteers and their clients. Themes
      emerging from the rich narratives included: companionship, independence, reduced
      anxiety, giving, and rewards. The article concludes with a suggested brief
      evaluation instrument that directors of SCP programs, and other similar programs,
      can use to collect data on the impact of their program--something that is
      required, but often difficult to do.

PMID- 16901878
TI  - Mapping your future--a proactive approach to aging.
AB  - As the number of older adults who live healthy and extended lives increases,
      people will need to envision the ways in which they choose to live. More emphasis
      will be given to the potential and strengths that older adults maintain in to
      later years rather than anticipating the consequences of decline. This paper
      describes the development of a tool to be used by older adults in planning their
      futures. It provides an individualized portfolio that encourages older adults to
      contemplate their future needs and resources. It includes the domains of health,
      work/leisure, finances, housing, and relationship/support systems. It is a means
      of encouraging conversations about life choices and maintaining a sense of
      empowerment and well-being.

PMID- 16901879
TI  - Nursing home complaints: who's complaining and what's gender got to do with it?
AB  - Long Term Care Ombudsman Complaint data from one state's 261 nursing homes are
      examined in the study. We assessed differences between male and female groups,
      including chiefly residents, but also ombudsmen, the residents' relatives or
      friends, administrators, legal representatives, and others regarding types and
      rates of complaints as reported in the Administration on Aging (AoA) major
      categories of: Resident Care, Resident Rights, Administration, Quality of Life,
      and Complaints Not Against Facility. Proportionately, male residents lodged more
      complaints than females. Further, males complained more than females about
      Resident Rights violations and filed more Complaints Not Against Facility.
      Females lodged significantly more complaints about Care, Quality of Life and
      Administration.Thus, males were more likely to report technical, impersonal, and
      legalistic issues, than females, who were more likely to express concerns about
      personal care and socioemotional-environmental issues. Results yielded further
      evidence of gender differences in the patterns of resident complaints. Nursing
      home social workers are highlighted as agents in changing embedded stereotypes
      about residents and complaints.

PMID- 16901880
TI  - Predictors of emotional strain among spouse and adult child caregivers.
AB  - This study used data from the 1999 National Long Term Care Survey to examine
      predictors of emotional strain between spouse and adult child caregivers using
      the frameworks of role theory and the stress process model. Secondary data
      analysis examined if and how emotional strain differed between the groups and
      what the predictors of emotional strain were for each group. Common group
      predictors of emotional strain were elder's disruptive behaviors, caregiver's
      perceived overload, family disagreement, limitations on the caregiver's life, and
      utilization of personal coping strategies by the caregiver. There were predictors
      unique to spouse's emotional strain but elders' race and respite availability
      were unique predictors of adult child caregiver's emotional strain. Ways in which
      predictors of emotional strain can be used to design effective and efficient
      social work interventions are discussed.

PMID- 16901881
TI  - Cultural attitudes and caregiver service use: lessons from focus groups with
      racially and ethnically diverse family caregivers.
AB  - Focus groups were conducted with caregivers from eight racial-specific or ethnic
      specific populations (African Americans, Chinese, Filipinos, Hispanics, Koreans,
      Native Americans, Russians, and Vietnamese), to examine cultural variations in
      caregiving experiences, care-related values and beliefs, care practices, and
      factors contributing to decisions about the use of caregiver support services.
      Analysis of focus group transcripts revealed three cross-cutting constructs:
      familism, group identity, and attitudinal and structural barriers to service use.
      We discuss these findings in terms of their implications for existing knowledge
      regarding family responsibility, resource utilization, and program development
      for racially and ethnically diverse family caregivers.

PMID- 16901882
TI  - An employee assistance program for caregiver support.
AB  - The Comprehensive Caregiver Choices Program provided support for employee
      caregivers of elderly people for employees at a hospital in Fort Worth, Texas.
      Key informant interviews and focus groups provided direction for program
      development and implementation. A full-time MSW and professionals with expertise
      in gerontology/geriatrics provided education and care coordination services to
      caregivers. Approximately 4% of the hospital's workforce participated in the
      program. Attendees evaluated educational sessions and follow-up interviews were
      conducted with program participants. Caregiver support programs must continue to
      seek innovative and creative marketing and service delivery methods to reach out
      and assist working caregivers in need of support.

PMID- 16901883
TI  - Increased wealth and income as correlates of self-assessed retirement.
AB  - This study examined whether retirement implies complete withdrawal from the labor
      force and the role that increased wealth and income play in regard to the nature
      of retirement. Data came from the Health & Retirement Study, Waves 1-5. Findings
      indicated that most study sample pre-retirees remained in the labor force as they
      moved into what are considered the normal retirement years. As they moved on
      average from 50+ years of age to 60+ years of age, increasing percentages of
      study sample pre-retirees reported themselves as completely retired. Those who
      viewed themselves as completely retired were far less likely to work than those
      who did not view themselves as completely retired. Of particular importance was
      the finding that increased income in 2000 decreased the likelihood of self
      reported complete retirement. Equally important was the finding that increased
      assets had no effect on retirement status with the exception of survey year 1998
      when increased assets decreased the likelihood of viewing oneself as completely
      retired. Findings suggested that pro-work retirement policies aimed at increasing
      labor force participation among pre-retirees and increasing the normal retirement
      age can be effective. Five pro-work policies were discussed.

PMID- 16901885
TI  - Trapped in captivity: marital perceptions of wives of former prisoners of war.
AB  - Knowledge on the experience of prisoners of war's (POWs) wives is sparse, and
      mostly concentrates on the first decade after captivity. The present qualitative
      study examined the marital perceptions of seven wives of POWs after three
      decades. Participants were recruited through therapists who worked with families
      of POWs. Data were collected by a semi-structured, in-depth focus group
      interview. The findings of the study shed light on: (1) The place of captivity in
      the life of the family over time and (2) the women's perception of their role and
      place in the marital relation as being responsible mainly for the husband's well
      being and the couple's relationship, while struggling to preserve their personal
      needs. The meaning of the results is discussed together with implications for
      practice.

PMID- 16901886
TI  - Domestic violence among Druze women in Israel as reflected by health status and
      somatization level.
AB  - Women with a history of physical or emotional abuse demonstrate a higher
      incidence of medical disorders but may be reluctant to disclose the abuse to
      health care providers. The present study explored whether measures of health
      status may serve as an indication of violence against women. Sixty-two Druze
      women (18-50 years old) completed health status (SF-36 survey), somatization
      (Brief Symptom Inventory-BSI), and abuse (the Abuse Assessment Screen-AAS)
      questionnaires during a visit to the family physician in the community primary
      care clinic. Higher somatization symptoms and diminished health status were
      associated with severity of violence. Results attest to the value of these
      measures as an additional indirect device for screening victims of domestic
      violence in general and among traditional societies in particular.

PMID- 16901887
TI  - Main partner's resistance to condoms and HIV protection among disadvantaged,
      minority women.
AB  - From a study of high-risk minority women, we examined data for a subgroup of 201
      women who participated in a "male condom- focused" HIV prevention intervention,
      and who reported having attempted to convince their main partner to use condoms
      in the 3 months following intervention. Factors related to consistent condom use
      with a main partner post-intervention were not living with the partner, fewer
      sexual encounters, and no recent sexual encounter in which either partner was
      under the influence of drugs. At 3 months following intervention, factors related
      to women's future intentions to use condoms consistently with a main partner were
      no recent sex while either partner was under the influence of drugs, and the
      woman's desire to use condoms consistently with the partner. Main partner's
      resistance to condoms was unrelated to consistent condom use or future intentions
      to use condoms consistently. Findings identify barriers to consistent condom use
      within primary relationships, a critical yet challenging focal point for HIV
      prevention interventions.

PMID- 16901888
TI  - Predictors of improvement in women's physical activity.
AB  - This study identified factors that predicted improved levels of physical activity
      in working women. Data were from a prospective, controlled trial. Sedentary women
      (N = 287) were recruited during an employer-sponsored health screening. The
      experimental group received a brief, tailored physical activity intervention as
      well as a booster phone call 2 weeks later. Participants were evaluated by
      comparing pre-test/post-test measures at 6-week follow-up. It was hypothesized
      that variables in the Transtheoretical Model (baseline stage of change, perceived
      pros, cons, and self-efficacy), as well as demographic variables and physical
      characteristics would predict improved physical activity. In addition, the study
      tested whether increased physical activity changed the variables of the
      Transtheoretical Model. Factors that correlated to improved physical activity
      were entered into regression models to determine predictors of improved physical
      activity. Being assigned to the intervention group was a significant predictor in
      all of the regression models. Women who increased their stage of change of
      physical activity had greater improvement in self-efficacy (p = .013). Minority
      women showed greater improvement in stage of change of physical activity (p =
      .001) as well as week-end physical activity (p = .042). Women with less education
      were more likely to increase total minutes walked per week (p = .038). The
      research suggests that these cognitive and demographic variables are important
      for improving levels of physical activity. The Transtheoretical Model was
      partially supported by the analyses.

PMID- 16901889
TI  - Relations of self-motivation, perceived physical condition, and exercise-induced
      changes in revitalization and exhaustion with attendance in women initiating a
      moderate cardiovascular exercise regimen.
AB  - This field investigation tested relationships between personal characteristics,
      feeling state changes occurring after exercise, and attendance in females (N =
      50, Mage = 39 years) initiating a 12-week, 3 days/week cardiovascular, community
      wellness center-based exercise program. Self-motivation and changes in exercise
      induced revitalization demonstrated significant positive correlations with
      attendance (r = .28 and .31, respectively), while a significant negative
      correlation of exercise- induced physical exhaustion with attendance (r = -.28)
      was found. Entry of self-motivation and perceived physical condition into linear
      multiple regression analyses, along with changes in exercise-induced feelings,
      accounted for greater amounts of variance in attendance than either the personal
      characteristics or exercise-induced feeling changes alone. Substitution of an
      aggregate measure of exercise-induced feeling changes into regression equations
      further increased the explained variance in attendance to 17% and 19%. Findings
      suggest that researchers should account for both personal characteristics and
      exercise-induced feeling changes in developing a comprehensive model of physical
      activity behavior in women. Replication and implications for treatments intended
      to increase exercise were discussed.

PMID- 16901890
TI  - Physical activity before pregnancy and following childbirth in a multiethnic
      sample of healthy women in Hawaii.
AB  - PURPOSE: Investigate physical activity and related psychosocial factors reported
      by new mothers. METHODS: Women (N = 79) were surveyed to determine their physical
      activity patterns before and after childbirth. Barriers and facilitators of
      physical activity were also identified. FINDINGS: Most women (63%) were ethnic
      minorities, mean age was 31.8 +/- 5.5 years, and their infants' mean age was 8.2
      +/- 3.8 months. Combining women's reported physical activity before their
      pregnancy and after childbirth resulted in four significantly different groups:
      (1) 21.5% were inactive before and after birth; (2) 22.7% were active before and
      after; (3) 12.6% were inactive before, but active after birth; and (4) 43.0% were
      active before but inactive or irregularly active postpartum (p < .0003). Barriers
      to physical activity included personal issues, including lack of support from a
      spouse, and parenting duties. Facilitators to being active included social
      support for exercise and availability of childcare. CONCLUSIONS: New mothers are
      at high risk for inactivity and reductions in previously established levels of
      physical activity. They also have specific barriers and facilitators to being
      physically active. Future research should develop effective methods for
      increasing physical activity in mothers of infants.

PMID- 16901891
TI  - Identifying barriers and facilitating factors to improve screening mammography
      rates in women diagnosed with mental illness and substance use disorders.
AB  - Little is known about screening mammography rates among women diagnosed with
      mental illness-even though some studies have suggested that this population might
      be particularly vulnerable to breast cancer. The purpose of this pilot study was
      to identify facilitators and barriers to mammography among women diagnosed with
      mental illness and/or substance use disorders. Four focus groups were conducted,
      with a total of 26 women, ages 40-65 years, with mental illness and/ or substance
      use disorders. Analysis was performed using the grounded-theory editing approach.
      Several major themes emerged from the transcripts: (1) motivators for obtaining
      mammograms, (2) fears and concerns, (3) shame and embarrassment, (4) the clinical
      environment, (5) provider-patient communication, and (6) the need for increased
      patient education. A family history of breast cancer and/or cancer was the most
      powerful motivator among focus group participants for obtaining a mammogram.
      Doctor recommendations and referrals were also identified as key facilitating
      factors. The overall knowledge of mammography and breast cancer among these women
      suggested educational deficiencies-despite extensive breast cancer screening and
      awareness campaigns. The findings highlight the importance of patient education
      as well as the positive effects of physician recommendations to encourage
      patients to receive breast cancer screening.

PMID- 16901892
TI  - A direct interaction between actin and vimentin filaments mediated by the tail
      domain of vimentin.
AB  - The assembly and organization of the three major eukaryotic cytoskeleton
      proteins, actin, microtubules, and intermediate filaments, are highly
      interdependent. Through evolution, cells have developed specialized
      multifunctional proteins that mediate the cross-linking of these cytoskeleton
      filament networks. Here we test the hypothesis that two of these filamentous
      proteins, F-actin and vimentin filament, can interact directly, i.e. in the
      absence of auxiliary proteins. Through quantitative rheological studies, we find
      that a mixture of vimentin/actin filament network features a significantly higher
      stiffness than that of networks containing only actin filaments or only vimentin
      filaments. Maximum inter-filament interaction occurs at a vimentin/actin molar
      ratio of 3 to 1. Mixed networks of actin and tailless vimentin filaments show low
      mechanical stiffness and much weaker inter-filament interactions. Together with
      the fact that cells featuring prominent vimentin and actin networks are much
      stiffer than their counterparts lacking an organized actin or vimentin network,
      these results suggest that actin and vimentin filaments can interact directly
      through the tail domain of vimentin and that these inter-filament interactions
      may contribute to the overall mechanical integrity of cells and mediate
      cytoskeletal cross-talk.

PMID- 16901893
TI  - Control of MyoD function during initiation of muscle differentiation by an
      autocrine signaling pathway activated by insulin-like growth factor-II.
AB  - The insulin-like growth factors (IGFs) play key roles in muscle development,
      maintenance, and repair, but their mechanisms of action are incompletely defined.
      We previously identified an autocrine pathway involving production of IGF-II and
      activation of the IGF-I receptor, phosphatidylinositol 3-kinase, and Akt in
      myoblast differentiation induced by MyoD in 10T1/2 mesenchymal stem cells and
      found that blocking this pathway prevented differentiation (Wilson, E. M., Hsieh,
      M. M., and Rotwein, P. (2003) J. Biol. Chem. 278, 41109-41113). We now have
      analyzed regulation of MyoD function in this model system. Inhibition of IGF-II
      production impaired the transcriptional actions of MyoD, as seen by a 70-80%
      decline in activity of transfected reporter genes, including the myogenin and
      creatine kinase promoters, and by complete inhibition of transcription of the
      endogenous myogenin gene but had no effect on MyoD protein levels, post
      translational modifications, or nuclear localization, and neither blocked the
      rapid disappearance of the inhibitory molecule Id1 nor altered the nuclear
      expression or abundance of the MyoD binding partner E12/E47. Impaired signaling
      through the IGF-I receptor also did not decrease the ability of MyoD or E12/E47
      to bind to target DNA sites at the proximal myogenin promoter, as assessed by
      chromatin immunoprecipitation assay but, rather, blocked chromatin remodeling at
      this site, as indicated by reduced recruitment of co-activators p300 and P/CAF
      and diminished acetylation of histones H3 and H4. Taken together, these results
      show that IGF-II-initiated signaling through the insulin-like growth factor-I
      receptor targets transcriptional co-regulators that are essential co-factors for
      MyoD and suggests that the phosphatidylinositol 3-kinase-Akt pathway plays a key
      role in establishing an amplification cascade that is essential for sustaining
      the earliest events in muscle differentiation.

PMID- 16901894
TI  - A point mutation in the SH1 helix alters elasticity and thermal stability of
      myosin II.
AB  - Movement generated by the myosin motor is generally thought to be driven by
      distortion of an elastic element within the myosin molecule and subsequent
      release of the resulting strain. However, the location of this elastic element in
      myosin remains unclear. The myosin motor domain consists of four major subdomains
      connected by flexible joints. The SH1 helix is the joint that connects the
      converter subdomain to the other domains, and is thought to play an important
      role in arrangements of the converter relative to the motor. To investigate the
      involvement of the SH1 helix in elastic distortion in myosin, we have introduced
      a point mutation into the SH1 helix of Dictyostelium myosin II (R689H), which in
      human nonmuscle myosin IIA causes nonsyndromic hereditary deafness, DFNA17. The
      mutation resulted in a significant impairment in motile activities, whereas actin
      activated ATPase activity was only slightly affected. Single molecule mechanical
      measurements using optical trap showed that the step size was not shortened by
      the mutation, suggesting that the slower motility is caused by altered kinetics.
      The single molecule measurements demonstrated that the mutation significantly
      reduced cross-bridge stiffness. Motile activities produced by mixtures of wild
      type and mutant myosins also suggested that the mutation affected the elasticity
      of myosin. These results suggest that the SH1 helix is involved in modulation of
      myosin elasticity, presumably by modulating the converter flexibility. Consistent
      with this, the mutation was also shown to reduce thermal stability and induce
      thermal aggregation of the protein, which might be implicated in the disease
      process.

PMID- 16901895
TI  - TTLL7 is a mammalian beta-tubulin polyglutamylase required for growth of MAP2
      positive neurites.
AB  - Microtubules form a cytoskeletal framework that influences cell shape and
      provides structural support for the cell. Microtubules in the nervous system
      undergo a unique post-translational modification, polyglutamylation of the C
      termini of their tubulin subunits. The mammalian enzymes that perform beta
      tubulin polyglutamylation as well as their physiological functions in the
      neuronal tissue remain elusive. We report identification of a mammalian
      polyglutamylase with specificity for beta-tubulin as well as its distribution and
      function in neurite growth. To identify putative tubulin polyglutamylases, we
      searched tubulin tyrosine ligase-like (TTLL) proteins for those predominantly
      expressed in the nervous system. Of 13 TTLL proteins, TTLL7 was transcribed at
      the highest level in the nervous system. Recombinant TTLL7 catalyzed tubulin
      polyglutamylation with high preference to beta-tubulin in vitro. When expressed
      in HEK293T cells, TTLL7 demonstrated specificity for beta-tubulin and not for
      alpha-tubulin or nucleosome assembly protein 1. Consistent with these findings,
      knockdown of TTLL7 in a primary culture of superior cervical ganglion neurons
      caused a loss of polyglutamylated beta-tubulin. Following stimulation of PC12
      cells with nerve growth factor to differentiate, the level of TTLL7 increased
      concomitantly with polyglutamylation of beta-tubulin. Short interference RNA
      mediated knockdown of TTLL7 repressed nerve growth factor-stimulated MAP
      (microtubule-associated protein) 2-positive neurite growth in PC12 cells.
      Consistent with having a role in the growth of MAP2-positive neurites, TTLL7
      accumulated within a MAP2-enriched somatodendritic portion of superior cervical
      ganglion, as did polyglutamylated beta-tubulin. Anti-TTLL7 antibody revealed that
      TTLL7 was distributed in a somatodendritic compartment in the mouse brain. These
      findings indicate that TTLL7 is a beta-tubulin polyglutamylase and is required
      for the growth of MAP2-positive neurites in PC12 cells.

PMID- 16901896
TI  - The unorthodox SNAP50 zinc finger domain contributes to cooperative promoter
      recognition by human SNAPC.
AB  - Human small nuclear RNA gene transcription by RNA polymerases II and III depends
      upon promoter recognition by the SNAPC general transcription factor. DNA binding
      by SNAPC involves direct DNA contacts by the SNAP190 subunit in cooperation with
      SNAP50 and SNAP43. The data presented herein shows that SNAP50 plays an important
      role in DNA binding by SNAPC through its zinc finger domain. The SNAP50 zinc
      finger domain contains 15 cysteine and histidine residues configured in two
      potential zinc coordination arrangements. Individual alanine substitution of each
      cysteine and histidine residue demonstrated that eight sites are important for
      DNA binding by SNAPC. However, metal binding studies revealed that SNAPC contains
      a single zinc atom indicating that only one coordination site functions as a zinc
      finger. Of the eight residues critical for DNA binding, four cysteine residues
      were also essential for both U1 and U6 transcription by RNA polymerase II and
      III, respectively. Surprisingly, the remaining four residues, although critical
      for U1 transcription could support partial U6 transcription. DNA binding studies
      showed that defects in DNA binding by SNAPC alone could be suppressed through
      cooperative DNA binding with another member of the RNA polymerase III general
      transcription machinery, TFIIIB. These results suggest that these eight cysteine
      and histidine residues perform different functions during DNA binding with those
      residues involved in zinc coordination likely performing a dominant role in
      domain stabilization and the others involved in DNA binding. These data further
      define the unorthodox SNAP50 zinc finger region as an evolutionarily conserved
      DNA binding domain.

PMID- 16901897
TI  - Magnesium, essential for base excision repair enzymes, inhibits substrate binding
      of N-methylpurine-DNA glycosylase.
AB  - N-Methylpurine-DNA glycosylase (MPG) initiates base excision repair in DNA by
      removing a wide variety of alkylated, deaminated, and lipid peroxidation-induced
      purine adducts. MPG activity and other DNA glycosylases do not have an absolute
      requirement for a cofactor. In contrast, all downstream activities of major base
      excision repair proteins, such as apurinic/apyrimidinic endonuclease, DNA
      polymerase beta, and ligases, require Mg(2+). Here we have demonstrated that
      Mg(2+) can be significantly inhibitory toward MPG activity depending on its
      concentration but independent of substrate type. The pre-steady-state kinetics
      suggests that Mg(2+) at high but physiologic concentrations decreases the amount
      of active enzyme concentrations. Steady-state inhibition kinetics showed that
      Mg(2+) affected K(m), but not V(max), and the inhibition could be reversed by
      EDTA but not by DNA. At low concentration, Mg(2+) stimulated the enzyme activity
      only with hypoxanthine but not ethenoadenine. Real-time binding experiments using
      surface plasmon resonance spectroscopy showed that the pronounced inhibition of
      activity was due to inhibition in substrate binding. Nonetheless, the glycosidic
      bond cleavage step was not affected. These results altogether suggest that Mg(2+)
      inhibits MPG activity by abrogating substrate binding. Because Mg(2+) is an
      absolute requirement for the downstream activities of the major base excision
      repair enzymes, it may act as a regulator for the base excision repair pathway
      for efficient and balanced repair of damaged bases, which are often less toxic
      and/or mutagenic than their subsequent repair product intermediates.

PMID- 16901898
TI  - The protein kinase C delta catalytic fragment targets Mcl-1 for degradation to
      trigger apoptosis.
AB  - Proteolytic cleavage and subsequent activation of protein kinase C (PKC) delta is
      required for apoptosis induced by a variety of genotoxic agent, including UV
      radiation. In addition, overexpression of the constitutively active PKCdelta
      catalytic fragment (PKCdelta-cat) is sufficient to trigger Bax activation,
      cytochrome c release, and apoptosis. While PKCdelta is a key apoptotic effector,
      the downstream target(s) responsible for the mitochondrial apoptotic cascade are
      not known. We found that expression of the active PKCdelta-cat in HaCaT cells
      triggers a reduction in the anti-apoptotic protein Mcl-1, similar to UV
      radiation. The down-regulation of Mcl-1 induced by PKCdelta-cat was not at the
      mRNA level but was due to decreased protein half-life. Overexpression of Mcl-1
      protected HaCaT cells from both UV and PKCdelta-cat-induced apoptosis and blocked
      the release of cytochrome c from the mitochondria, indicating that Mcl-1 down
      regulation was required for apoptosis signaling. Indeed, down-regulation of Mcl-1
      with siRNA slightly increased the basal apoptotic rate of HaCaT cells and
      dramatically sensitized them to UV or PKCdelta-cat-induced apoptosis. HaCaT cells
      with down-regulated Mcl-1 had higher activated Bax protein, as measured by Bax
      cross-linking, indicating that Mcl-1 down-regulation is sufficient for Bax
      activation. Finally, recombinant PKCdelta could phosphorylate Mcl-1 in vitro,
      identifying Mcl-1 as a direct target for PKCdelta. Overall our results identify
      Mcl-1 as an important target for PKCdelta-cat that can mediate its pro-apoptotic
      effects on mitochondria to amplify the apoptotic signaling induced by a wide
      range of apoptotic stimuli.

PMID- 16901899
TI  - Biochemical fates of alpha hemoglobin bound to alpha hemoglobin-stabilizing
      protein AHSP.
AB  - Alpha hemoglobin-stabilizing protein (AHSP) is an erythroid protein that binds
      free alpha hemoglobin (alphaHb) to maintain its structure and limit its pro
      oxidant activity. Prior studies have defined two different alphaHb.AHSP
      complexes. Binding of AHSP to Fe(II) alphaHb induces an unusual configuration in
      which the F helix of the globin becomes disordered and the heme ring becomes
      solvent-exposed. Over time, this intermediate oxidizes to form a stable
      hemichrome in which the proximal (F8) and distal (E7) histidines are coordinated
      to the heme iron atom. The addition of betaHb to either Fe(II) or Fe(III)
      alphaHb.AHSP displaces AHSP to generate tetrameric (alpha(2)beta(2)) HbA species.
      The biochemical properties and in vivo significance of the two alphaHb.AHSP
      complexes are poorly understood. Here we show that Fe(III) alphaHb.AHSP forms
      from auto-oxidation of oxygenated alphaHb bound to AHSP and that this process is
      greatly accelerated at physiologic temperature and oxygen pressures. In contrast
      to free Fe(III) alphaHb hemichromes, AHSP-bound Fe(III) alphaHb does not
      precipitate and can be recycled into functional HbA. This requires enzymatic
      reduction of AHSP-bound alphaHb, either prior to or after extraction by beta
      subunits. In contrast, reaction of Fe(II) alphaHb-AHSP with betaHb generates
      functional HbA directly. Our findings support a model in which AHSP can either
      stabilize alphaHb transiently en route to HbA formation during normal
      erythropoiesis or convert excessive free alphaHb into a more chemically inert
      state from which recovery of alphaHb is possible by redox cycling.

PMID- 16901900
TI  - Endoplasmic reticulum stress triggers autophagy.
AB  - Eukaryotic cells have evolved strategies to respond to stress conditions. For
      example, autophagy in yeast is primarily a response to the stress of nutrient
      limitation. Autophagy is a catabolic process for the degradation and recycling of
      cytosolic, long lived, or aggregated proteins and excess or defective organelles.
      In this study, we demonstrate a new pathway for the induction of autophagy. In
      the endoplasmic reticulum (ER), accumulation of misfolded proteins causes stress
      and activates the unfolded protein response to induce the expression of
      chaperones and proteins involved in the recovery process. ER stress stimulated
      the assembly of the pre-autophagosomal structure. In addition, autophagosome
      formation and transport to the vacuole were stimulated in an Atg protein
      dependent manner. Finally, Atg1 kinase activity reflects both the nutritional
      status and autophagic state of the cell; starvation-induced autophagy results in
      increased Atg1 kinase activity. We found that Atg1 had high kinase activity
      during ER stress-induced autophagy. Together, these results indicate that ER
      stress can induce an autophagic response.

PMID- 16901901
TI  - Laforin, a dual specificity phosphatase that dephosphorylates complex
      carbohydrates.
AB  - Laforin is the only phosphatase in the animal kingdom that contains a
      carbohydrate-binding module. Mutations in the gene encoding laforin result in
      Lafora disease, a fatal autosomal recessive neurodegenerative disorder, which is
      diagnosed by the presence of intracellular deposits of insoluble complex
      carbohydrates known as Lafora bodies. We demonstrate that laforin interacts with
      proteins known to be involved in glycogen metabolism and rule out several of
      these proteins as potential substrates. Surprisingly, we find that laforin
      displays robust phosphatase activity against a phosphorylated complex
      carbohydrate. Furthermore, this activity is unique to laforin, since several
      other phosphatases are unable to dephosphorylate polysaccharides. Finally, fusing
      the carbohydrate-binding module of laforin to the dual specific phosphatase VHR
      does not result in the ability of this phosphatase to dephosphorylate
      polysaccharides. Therefore, we hypothesize that laforin is unique in its ability
      to utilize a phosphorylated complex carbohydrate as a substrate and that this
      function may be necessary for the maintenance of normal cellular glycogen.

PMID- 16901902
TI  - Conformation of amyloid fibrils of beta2-microglobulin probed by tryptophan
      mutagenesis.
AB  - Beta2-microglobulin (beta2-m), a protein responsible for dialysis-related
      amyloidosis, adopts an immunoglobulin domain fold in its native state. Although
      beta2-m has Trp residues at positions 60 and 95, both are located near the
      surface of the domain. Hence, beta2-m does not have a conserved Trp common to
      other immunoglobulin domains, which is buried in close proximity to the disulfide
      bond. To study the structure of amyloid fibrils in relation to their native fold,
      we prepared a series of Trp mutants. Trp60 and Trp95 were both replaced with Phe,
      and a single Trp was introduced at various positions. Among various mutants, W39
      beta2-m, in which a Trp was introduced at the position corresponding to the
      conserved Trp, exhibited a remarkable quenching of fluorescence in the native
      state, as observed for other immunoglobulin domains. An x-ray structural analysis
      revealed that W39-beta2-m assumes the native fold with Trp39 located in the
      vicinity of the disulfide bond. Comparison of the fluorescence spectra of various
      mutants for the native and fibrillar forms indicated that, while the Trp residues
      introduced in the middle of the beta2-m sequence tend to be buried in the
      fibrils, those located in the C-terminal region are more exposed. In addition,
      the fluorescence spectra of fibrils prepared at pH 2.5 and 7.0 revealed a large
      difference in the fluorescence intensity for W60-beta2-m, implying a major
      structural difference between them.

PMID- 16901903
TI  - Transcriptional regulation of ULBP1, a human ligand of the NKG2D receptor.
AB  - Tumor cells expressing ligands of the NKG2D receptor stimulate anti-tumor
      immunity mediated by natural killer and T cells. In humans, NKG2D ligands
      (NKG2DL) are encoded by MIC and ULBP proteins. NKG2DL exhibit highly restricted
      expression in healthy tissues but are widely expressed in tumors. However,
      regulation of each NKG2DL differs substantially in different cancer cells. In
      this study, we characterized the mechanisms that regulate the expression of
      ULBP1. We show that the transcription of ULBP1 strictly depends on the binding of
      Sp1 and Sp3 to a CRE(1) site located in the ULBP1 minimal promoter. The mutation
      or deletion of this Sp1/Sp3 binding site abolished the transcription of ULBP1. It
      also diminished the transactivation of ULBP1 promoter by Sp3 overexpression, but
      not by Sp1, indicating that Sp3 is the main transcription factor that regulates
      ULBP1 through the CRE(1) site. Experiments in SL2 cells showed that the ULBP1
      promoter was inactive in the absence of the Sp proteins and indicate that Sp3 is
      the essential activator of ULBP1 transcription, because the overexpression of Sp3
      up-regulated its promoter activity > 500-fold. Additionally, we demonstrated that
      AP-2alpha repressed the expression of ULBP1 in HeLa cells by interfering with the
      binding of Sp3 and Sp1 to the ULBP1 promoter. These data indicate that Sp1, Sp3,
      and AP-2alpha may play an important role in the immunosurveillance against
      cancer. Finally, the definition of ULBP1 regulation may have implications for
      development of new therapeutic strategies against cancer cells.

PMID- 16901904
TI  - The tyrosine kinase c-Abl protects c-Jun from ubiquitination-mediated degradation
      in T cells.
AB  - The cross-talk of ubiquitination with other types of posttranscriptional
      modifications, such as phosphorylation, regulates the stability of many proteins.
      We have previously demonstrated that c-Jun is a substrate of Itch, a HECT-type E3
      ubiquitin ligase. c-Jun is also a substrate of the tyrosine kinase c-Abl. Here we
      report that genetic ablation of c-Abl accelerated c-Jun degradation.
      Phosphorylation of the tyrosine within the PPXY motif by c-Abl inhibited c-Jun
      ubiquitination and its binding by Itch. The nuclear localization of c-Abl,
      triggered by T-cell activation signals, was essential for its activity in
      regulating c-Jun transcription activity. These findings define a potential
      molecular mechanism for the immunodeficiency in mice lacking the c-abl gene.

PMID- 16901905
TI  - Targeting protein kinase C activity reporter to discrete intracellular regions
      reveals spatiotemporal differences in agonist-dependent signaling.
AB  - Protein kinase C (PKC) family members transduce an abundance of diverse
      intracellular signals. Here we address the role of spatial and temporal
      segregation in signal specificity by measuring the activity of endogenous PKC at
      defined intracellular locations in real time in live cells. We targeted a
      genetically encoded fluorescence resonance energy transfer-based reporter for PKC
      activity, C kinase activity reporter (CKAR) (Violin, J. D., Zhang, J., Tsien, R.
      Y., and Newton, A. C. (2003) J. Cell Biol. 161, 899-909), to the plasma membrane,
      Golgi, cytosol, mitochondria, or nucleus by fusing appropriate targeting
      sequences to the NH2 or COOH terminus of CKAR. Measuring the phosphorylation of
      the reporter in the presence of PKC inhibitors, activators, and/or phosphatase
      inhibitors shows that activity at each region is under differential control by
      phosphatase activity; nuclear activity is completely suppressed by phosphatases,
      whereas membrane-associated activity is the least suppressed by phosphatases. UTP
      stimulation of endogenous P2Y receptors in COS 7 cells reveals spatiotemporally
      divergent PKC responses. Imaging the second messengers Ca2+ and diacylglycerol
      (DAG) reveal that PKC activity at each location is driven by an initial spike in
      Ca2+, followed by location-specific diacylglycerol generation. In response to
      UTP, phosphorylation of GolgiCKAR was sustained the longest, driven by the
      persistence of DAG, whereas phosphorylation of CytoCKAR was of the shortest
      duration, driven by high phosphatase activity. Our data reveal that the magnitude
      and duration of PKC signaling is location-specific and controlled by the level of
      phosphatase activity and persistence of DAG at each location.

PMID- 16901906
TI  - Antisense inhibition of RNase P: mechanistic aspects and application to live
      bacteria.
AB  - We explored bacterial RNase P as a drug target using antisense oligomers against
      the P15 loop region of Escherichia coli RNase P RNA. An RNA 14-mer, or locked
      nucleic acid (LNA) and peptide nucleic acid (PNA) versions thereof, disrupted
      local secondary structure in the catalytic core, forming hybrid duplexes over
      their entire length. Binding of the PNA and LNA 14-mers to RNase P RNA in vitro
      was essentially irreversible and even resisted denaturing PAGE. Association rates
      for the RNA, LNA, and PNA 14-mers were approximately 10(5) m(-1) s(-1) with a
      rate advantage for PNA and were thus rather fast despite the need to disrupt
      local structure. Conjugates in which the PNA 14-mer was coupled to an invasive
      peptide via a novel monoglycine linker showed RNase P RNA-specific growth
      inhibition of E. coli cells. Cell growth could be rescued when expressing a
      second bacterial RNase P RNA with an unrelated sequence in the target region. We
      report here for the first time specific and growth-inhibitory drug targeting of
      RNase P in live bacteria. This is also the first example of a duplex-forming
      oligomer that invades a structured catalytic RNA and inactivates the RNA by (i)
      trapping it in a state in which the catalytic core is partially unfolded, (ii)
      sterically interfering with substrate binding, and (iii) perturbing the
      coordination of catalytically relevant Mg2+ ions.

PMID- 16901907
TI  - Neuroglycan C is a novel midkine receptor involved in process elongation of
      oligodendroglial precursor-like cells.
AB  - Midkine is a heparin-binding growth factor that promotes cell attachment and
      process extension in undifferentiated bipolar CG-4 cells, an oligodendroglial
      precursor cell line. We found that CG-4 cells expressed a non-proteoglycan form
      of neuroglycan C, known as a part-time transmembrane proteoglycan. We
      demonstrated that neuroglycan C before or after chondroitinase ABC treatment
      bound to a midkine affinity column. Neuroglycan C lacking chondroitin sulfate
      chains was eluted with 0.5 m NaCl as a major fraction from the column. We
      confirmed that CG-4 cells expressed two isoforms of neuroglycan C, I, and III, by
      isolating cDNA. Among three functional domains of the extracellular part of
      neuroglycan C, the chondroitin sulfate attachment domain and acidic amino acid
      cluster box domain showed affinity for midkine, but the epidermal growth factor
      domain did not. Furthermore, cell surface neuroglycan C could be cross-linked
      with soluble midkine. Process extension on midkine-coated dishes was inhibited by
      either a monoclonal anti-neuroglycan C antibody C1 or a glutathione S-transferase
      neuroglycan C fusion protein. Finally, stable transfectants of B104 neuroblastoma
      cells overexpressing neuroglycan C-I or neuroglycan C-III attached to the midkine
      substrate, spread well, and gave rise to cytoskeletal changes. Based on these
      results, we conclude that neuroglycan C is a novel component of midkine receptors
      involved in process elongation.

PMID- 16901908
TI  - Receptor-induced activation of Drosophila TRP gamma by polyunsaturated fatty
      acids.
AB  - Cellular calcium homeostasis is regulated by hormones and neurotransmitters,
      resulting in the activation of a variety of proteins, in particular, channel
      proteins of the plasma membrane and of intracellular compartments. Such channels
      are, for example, TRP channels of the TRPC protein family that are activated by
      various mediators from receptor-stimulated signaling cascades. In Drosophila, two
      TRPC channels, TRP and TRPL, are involved in phototransduction. In addition, a
      third Drosophila TRPC channel, TRPgamma, has been identified and described as an
      auxiliary subunit of TRPL. Beyond it, our data show that heterologously expressed
      TRPgamma formed a receptor-activated, outwardly rectifying cation channel
      independent from TRPL co-expression. Analysis of the activation mechanism
      revealed that TRPgamma is activated by various polyunsaturated fatty acids
      generated in a phospholipase C- and phospholipase A(2)-dependent manner. The most
      potent activator of TRPgamma, the stable analogue of arachidonic acid, 5,8,11,14
      eicosatetraynoic acid, induced currents in single channel recordings. Here we
      show that upon heterologous expression TRPgamma forms a homomeric channel complex
      that is activated by polyunsaturated fatty acids as mediators of receptor
      dependent signaling pathways. Reverse transcription PCR analysis showed that
      TRPgamma is expressed in Drosophila heads and bodies. Its body-wide expression
      pattern and its activation mechanism suggest that TRPgamma forms a fly cation
      channel responsible for the regulation of intracellular calcium in a variety of
      hormonal signaling cascades.

PMID- 16901909
TI  - Brain-derived neurotrophic factor (BDNF)-induced synthesis of early growth
      response factor 3 (Egr3) controls the levels of type A GABA receptor alpha 4
      subunits in hippocampal neurons.
AB  - Altered function of gamma-aminobutyric acid type A receptors (GABA(A)Rs) in
      dentate granule cells of the hippocampus has been associated with temporal lobe
      epilepsy (TLE) in humans and in animal models of TLE. Such altered receptor
      function (including increased inhibition by zinc and lack of modulation by
      benzodiazepines) is related, in part, to changes in the mRNA levels of certain
      GABA(A)R subunits, including alpha4, and may play a role in epileptogenesis. The
      majority of GABA(A)Rs that contain alpha4 subunits are extra-synaptic due to lack
      of the gamma2 subunit and presence of delta. However, it has been hypothesized
      that seizure activity may result in expression of synaptic receptors with altered
      properties driven by an increased pool of alpha4 subunits. Results of our
      previous work suggests that signaling via protein kinase C (PKC) and early growth
      response factor 3 (Egr3) is the plasticity trigger for aberrant alpha4 subunit
      gene (GABRA4) expression after status epilepticus. We now report that brain
      derived neurotrophic factor (BDNF) is the endogenous signal that induces Egr3
      expression via a PKC/MAPK-dependent pathway. Taken together with the fact that
      blockade of tyrosine kinase (Trk) neurotrophin receptors reduces basal GABRA4
      promoter activity by 50%, our findings support a role for BDNF as the mediator of
      Egr3-induced GABRA4 regulation in developing neurons and epilepsy and, moreover,
      suggest that BDNF may alter inhibitory processing in the brain by regulating the
      balance between phasic and tonic inhibition.

PMID- 16901910
TI  - Planning and implementing a community-based public health advocacy campaign: a
      transport case study from Australia.
AB  - Facilitating community action is a key goal of health promotion. This paper
      describes a public health advocacy framework. It then presents a case study of
      its application for planning community action by a community alliance concerned
      about increased heavy traffic on roads through a small regional city in the South
      West region of Western Australia. The case study illustrates defining the public
      health problem, the solution and the target for action; and the implementation of
      a comprehensive range of strategies including a media advocacy strategy to
      attract public attention, to reframe media messages, and to provide a policy
      alternative to government and industry. The campaign was evaluated in terms of
      process and outcomes, and was successful in putting pressure on key stakeholders
      and achieving the alliance's two main goals. The case study demonstrates the
      value of a well-planned campaign and including public health advocacy in public
      health practice, as an important strategy to facilitate the creation of healthy
      environments through healthy public policy.

PMID- 16901911
TI  - Pharmacokinetics and pharmacodynamics of weekly epoetin beta in lung cancer
      patients.
AB  - BACKGROUND: To assess the pharmacokinetic profile and time-course of trough
      concentrations and hemoglobin levels associated with subcutaneous weekly
      administration of epoetin beta in lung cancer patients with chemotherapy-induced
      anemia. METHODS: Epoetin beta was subcutaneously administered to 15 anemic lung
      cancer patients once weekly for 8 weeks at doses of 9000, 18,000 and 36,000 IU.
      Pharmacokinetic parameters (C(max), AUC(inf) and T(1/2)) were determined after
      the first single dose administration on a model-independent basis, and the
      relationship between the dose and these parameters was examined for linearity.
      RESULTS: Weekly administration of epoetin beta at 9000, 18,000 and 36,000 IU
      produced C(max) values of 308 +/- 117 (mean +/- standard deviation), 678 +/- 86.7
      and 1316 +/- 766 mIU/ml, and AUC(inf) values of 15,300 +/- 9524, 54,574 +/-
      16,265 and 88,501 +/- 55,687 hr mIU/ml, respectively, showing dose-proportional
      increases. Trough concentrations tended to increase in the presence of severe
      bone marrow suppression induced by chemotherapy or other factors. Extremely high
      values were seen in three patients, but there was no apparent trend toward an
      increase with repeated doses. After 8 weeks' administration at 9000, 18,000 and
      36,000 IU, hemoglobin levels were changed by -0.37 +/- 1.26, 2.15 +/- 1.36 and
      2.82 +/- 2.17 g/dl, respectively. CONCLUSIONS: Epoetin beta exhibited linear
      pharmacokinetics when administered to anemic cancer patients at weekly doses of
      9000-36,000 IU and did not cause drug accumulation. Hemoglobin levels increased
      with weekly doses of 18,000 or 36,000 IU.

PMID- 16901912
TI  - Evolution of extended-spectrum beta-lactamases in a MutS-deficient Pseudomonas
      aeruginosa hypermutator.

PMID- 16901913
TI  - Nerve excitability changes in critical illness polyneuropathy.
AB  - Patients in intensive care units frequently suffer muscle weakness and atrophy
      due to critical illness polyneuropathy (CIP), an axonal neuropathy associated
      with systemic inflammatory response syndrome and multiple organ failure. CIP is a
      frequent and serious complication of intensive care that delays weaning from
      mechanical ventilation and increases mortality. The pathogenesis of CIP is not
      well understood and no specific therapy is available. The aim of this project was
      to use nerve excitability testing to investigate the changes in axonal membrane
      properties occurring in CIP. Ten patients (aged 37-76 years; 7 males, 3 females)
      were studied with electrophysiologically proven CIP. The median nerve was
      stimulated at the wrist and compound action potentials were recorded from
      abductor pollicis brevis muscle. Strength-duration time constant, threshold
      electrotonus, current-threshold relationship and recovery cycle (refractoriness,
      superexcitability and late subexcitability) were recorded using a recently
      described protocol. In eight patients a follow-up investigation was performed.
      All patients underwent clinical examination and laboratory investigations.
      Compared with age-matched normal controls (20 subjects; aged 38-79 years; 7
      males, 13 females), CIP patients exhibited reduced superexcitability at 7 ms,
      from -22.3 +/- 1.6% to -7.6 +/- 3.1% (mean +/- SE, P approximately 0.0001) and
      increased accommodation to depolarizing (P < 0.01) and hyperpolarizing currents
      (P < 0.01), indicating membrane depolarization. Superexcitability was reduced
      both in patients with renal failure and without renal failure. In the former,
      superexcitability correlated with serum potassium (R = 0.88), and late
      subexcitability was also reduced (as also occurs owing to hyperkalaemia in
      patients with chronic renal failure). In patients without renal failure, late
      subexcitability was normal, and the signs of membrane depolarization correlated
      with raised serum bicarbonate and base excess, indicating compensated respiratory
      acidosis. It is inferred that motor axons in these CIP patients are depolarized,
      in part because of raised extracellular potassium, and in part because of
      hypoperfusion. The chronic membrane depolarization may contribute to the
      development of neuropathy.

PMID- 16901914
TI  - Neuroprotection by PlGF gene-modified human mesenchymal stem cells after cerebral
      ischaemia.
AB  - Intravenous delivery of mesenchymal stem cells (MSCs) prepared from adult bone
      marrow reduces infarction size and ameliorates functional deficits in rat
      cerebral ischaemia models. Placental growth factor (PlGF) is angiogenic to
      impaired non-neural tissue. To test the hypothesis that PlGF contributes to the
      therapeutic benefits of MSC delivery in cerebral ischaemia, we compared the
      efficacy of systemic delivery of human MSCs (hMSCs) and hMSCs transfected with a
      fibre-mutant F/RGD adenovirus vector with a PlGF gene (PlGF-hMSCs). A permanent
      middle cerebral artery occlusion (MCAO) was induced by intraluminal vascular
      occlusion with a microfilament. hMSCs and PlGF-hMSCs were intravenously injected
      into the rats 3 h after MCAO. Lesion size was assessed at 3 and 6 h, and 1, 3, 4
      and 7 days using MR imaging and histology. Functional outcome was assessed using
      the limb placement test and the treadmill stress test. Both hMSCs and PlGF-hMSCs
      reduced lesion volume, induced angiogenesis and elicited functional improvement
      compared with the control sham group, but the effect was greater in the PlGF-hMSC
      group. Enzyme-linked immunosorbent assay of the infarcted hemisphere revealed an
      increase in PlGF in both hMSC groups, but a greater increase in the PlGF-hMSC
      group. These data support the hypothesis that PlGF contributes to neuroprotection
      and angiogenesis in cerebral ischaemia, and cellular delivery of PlGF to the
      brain can be achieved by intravenous delivery of hMSCs.

PMID- 16901915
TI  - Global transmission of prolyliminopeptidase-negative Neisseria gonorrhoeae
      strains: implications for changes in diagnostic strategies.
AB  - BACKGROUND: Species confirmation of Neisseria gonorrhoeae is commonly performed
      with biochemical kits, rely on the activity of the enzyme prolyliminopeptidase
      (PIP). This enzyme has previously been considered to be almost universally
      present in N gonorrhoeae. However, increasing numbers of N gonorrhoeae isolates
      lacking PIP activity have been identified. OBJECTIVES: To investigate the
      possibility of a widespread transmission of one or several N gonorrhoeae PIP
      negative strains among several countries worldwide. METHODS: PIP-negative N
      gonorrhoeae isolates cultured from 2001 to 2004 in Australia, New Zealand and
      Scotland were comprehensively characterised and compared with previous data from
      England and Denmark. All isolates were characterised by antibiotic susceptibility
      testing, serovar determination, pulsed-field gel electrophoresis (PFGE), opa
      typing, sequencing of the entire porB gene and N gonorrhoeae multiantigen
      sequence typing (NG-MAST). RESULTS: Most (83%) of the viable Australian isolates,
      and all the New Zealand and Scottish isolates were assigned serovar IB-4, with
      similar antibiograms, nearly identical porB1b gene sequences, identical (ST210)
      or highly related (ST292, ST1259) NG-MAST STs, and indistinguishable or related
      PFGE fingerprints as well as opa-types. The isolates showed characteristics
      indistinguishable or highly related to the previously described English and
      Danish outbreak strain. CONCLUSIONS: A comprehensive characterisation indicates a
      widespread dissemination, mainly among men who have sex with men (MSM), of
      indistinguishable and highly related genotypes that have evolved from a single N
      gonorrhoeae PIP-negative serovar IB-4 strain among several countries worldwide.
      An increased awareness of PIP-negative N gonorrhoeae strains is crucial and
      changes in the diagnostic strategies may need to be considered.

PMID- 16901916
TI  - How, not just if, condoms are used: the timing of condom application and removal
      during vaginal sex among young people in England.
AB  - OBJECTIVE: To assess the prevalence of, and factors associated with, vaginal
      penetration before condom application and following condom removal among young
      people in education in England. METHOD: A large cross sectional survey (n = 1373)
      was conducted in educational establishments in England and sexual event diaries
      were completed by a subsample of young people over a 6 month period. RESULTS: Of
      the 375 survey respondents who reported having used a condom on the most recent
      occasion of vaginal sex, 6% had applied the condom after penetration and 6% had
      continued penetration after condom removal. Of the 74 diary respondents, 31%
      applied a condom late and 9% removed a condom early at least once over a 6 month
      period. The odds of "imperfect" condom use were found to decrease with overall
      consistency of condom use, confidence in correct condom use, positive reported
      relationship with mother, non-use of other contraception, and desire to use a
      condom. CONCLUSION: Given that late application and early removal of condoms fail
      to maximise their effectiveness as a method of STI prevention, it is important to
      address "imperfect" condom use and the factors associated with such use in public
      health policies and programmes. It is essential that young people understand the
      importance of using condoms consistently and correctly, and are also equipped
      with the skills and knowledge to do so.

PMID- 16901917
TI  - Prevalence and correlates of exchanging sex for drugs or money among adolescents
      in the United States.
AB  - OBJECTIVE: This study examined the prevalence and correlates of exchanging sex
      for drugs or money among a nationally representative sample of 13,294 adolescents
      in the United States. METHODS: Data are from the National Longitudinal Study of
      Adolescent Health, waves I and II. The lifetime prevalence of exchanging sex was
      estimated and a cross sectional analysis of sociodemographic and behavioural
      correlates was conducted. Unadjusted odds ratios were obtained. RESULTS: 3.5% of
      adolescents had ever exchanged sex for drugs or money. Two thirds of these youths
      were boys. The odds of having exchanged sex were higher for youths who had used
      drugs, had run away from home, were depressed, and had engaged in various sexual
      risk behaviours. 15% of boys and 20% of girls who had exchanged sex reported they
      had ever been told they have HIV or another sexually transmitted infection (STI).
      CONCLUSIONS: Adolescents with a history of exchanging sex have engaged in other
      high risk behaviours and may experience poor health outcomes, including
      depression and HIV/STIs. These findings should help inform strategies to prevent
      this high risk sexual behaviour and its potential consequences.

PMID- 16901918
TI  - Risk factors associated with pelvic inflammatory disease.
AB  - OBJECTIVE: To investigate factors associated with pelvic inflammatory disease
      (PID). METHODS: A case-control study was used to investigate demographic and
      behavioural factors, and causative agents associated with PID. RESULTS: A total
      of 381 participants were recruited: 140 patients, and 105 and 136 controls in
      tubal ligation and general practice groups, respectively. When compared with a
      PID-free tubal ligation control group, increased risk of PID was associated with:
      age <25 years; age at first sexual intercourse <20 years; non-white ethnicity;
      not having had children; a self-reported history of a sexually transmitted
      disease; and exposure to Chlamydia trachomatis. When compared with a general
      practice control group, increased risk was associated with: age <25 years; age at
      first sexual intercourse <15 years; lower socioeconomic status; being single;
      adverse pregnancy outcome; a self-reported history of a sexually transmitted
      disease; and exposure to C trachomatis. Of the cases, 64% were not associated
      with any of the infectious agents measured in this study (idiopathic).
      CONCLUSIONS: A high proportion of cases were idiopathic. PID control strategies,
      which currently focus on chlamydial screening, have to be reviewed so that they
      can prevent all cases of PID. Behavioural change is a key factor in the primary
      prevention of PID, and potential modifiable risk factors were associated with
      PID.

PMID- 16901919
TI  - Pigment epithelium-derived factor downregulates vascular endothelial growth
      factor (VEGF) expression and inhibits VEGF-VEGF receptor 2 binding in diabetic
      retinopathy.
AB  - It has been shown that the balance between vascular endothelial growth factor
      (VEGF), a major angiogenic stimulator, and pigment epithelium-derived factor
      (PEDF), a potent angiogenic inhibitor, is critical for the regulation of vascular
      permeability and angiogenesis. However, the regulation of the balance is largely
      unclear. The present study demonstrated that there is a reciprocal interaction
      between VEGF and PEDF in the retina. PEDF significantly decreased VEGF expression
      in both retinal capillary endothelial cells (RCEC) and Muller cells. This PEDF
      effect was confirmed in the retina of rats with oxygen-induced retinopathy.
      Silencing of the PEDF gene by siRNA in Muller cells resulted in a significant
      upregulation of VEGF expression at both the RNA and protein levels, suggesting
      that PEDF is an endogenous negative regulator of VEGF. The further study of the
      mechanism showed that PEDF inhibited hypoxia-induced increases in VEGF promoter
      activity, HIF-1 nuclear translocation and mitogen activated protein kinase
      phosphorylation. These results suggest that PEDF inhibits VEGF expression at the
      transcriptional level. In addition, PEDF effectively inhibited VEGF binding to
      RCEC. Moreover, in vitro receptor-binding assay demonstrated that PEDF competed
      with VEGF for binding to VEGF receptor 2, which may represent a new mechanism for
      PEDF activity. On the other hand, VEGF significantly downregulated PEDF
      expression in RCEC, but not in retinal Muller cells, suggesting a VEGF receptor
      mediated process. These results suggest that the reciprocal regulation between
      VEGF and PEDF may play a role in angiogenic control. The decrease in PEDF levels
      in the retina is at least partially responsible for the increase in VEGF
      expression and subsequent vascular leakage and neovascularization in diabetes.

PMID- 16901920
TI  - IGF-independent effects of IGFBP-2 on the human breast cancer cell line Hs578T.
AB  - There is evidence that insulin-like growth factor-binding protein (IGFBP-2), a
      modulator of the actions of IGFs, also has IGF-independent effects in human tumor
      cell lines. These involve specific binding of IGFBP-2 to alpha5beta1-integrin,
      followed by alterations in the phosphorylation status of downstream signaling
      molecules. Previously, IGFBP-2 has also been shown to be associated with cell
      proliferation, adhesion and migration. Here, we investigated direct effects of
      IGFBP-2 on apoptosis and alterations in the expression of related proteins. The
      breast cancer cell line Hs578T, which shows no IGFBP-2 production of its own and
      is independent of the IGF-I receptor, was treated with human recombinant IGFBP-2
      in order to study the changes in gene expression induced by IGFBP-2. The methods
      employed for this purpose were oligonucleotide microarrays, real-time RT-PCR,
      western blotting, and immunoassays. Out of the 440 genes covered by the Oligo
      GEArray Human Cancer Microarray OHS-802, the expression of 77 genes was directly
      influenced by IGFBP-2. By the use of real-time quantitative RT-PCR, the gene
      expression of Nuclear Factor (NF)kappaB, p53, transforming growth factor beta
      (TGF beta-1), LAMB1 (Laminin, Beta 1), Bcl-2, and IIp45 was found to be
      significantly upregulated (by 1.2- to 3.05-fold; all P < 0.001). Accordingly,
      NFkappaB, p53, and TGF beta-1 proteins, as measured by Western blotting and
      immunoassay, were upregulated > 1.5-fold. By using an ELISA-based and a flow
      cytometry-based apoptosis assay, IGFBP-2 was found to have a pro-apoptotic effect
      on Hs578T cells. Our results suggest that IGFBP-2-induced gene expressions are of
      functional significance for proliferation, cell adhesion, cell migration and
      apoptosis, and showed that IGFBP-2 can promote apoptosis in tumor cells
      independent of IGF.

PMID- 16901921
TI  - Examination of the direct effects of metabolic factors on somatotrope function in
      a non-human primate model, Papio anubis.
AB  - In humans, circulating GH levels are increased in catabolic states and suppressed
      in obesity. In both extremes, normalization of the metabolic environment
      normalizes GH release, leading to the conclusion that changes in metabolic
      hormones and/or metabolites promote changes in GH synthesis and release.
      Metabolic regulation of GH secretion can be mediated centrally by modulation of
      hypothalamic GHRH and somatostatin input to the pituitary and/or by direct
      regulation of pituitary somatotrope function. Although data are available showing
      glucocorticoids, free fatty acids (FFA), IGF-I, and insulin have direct effects
      on rat somatotrope function, little information is available regarding the direct
      pituitary effects of these metabolic factors in primates. Therefore, this study
      examined the effects of glucocorticoids (dexamethasone (0.1-100 nM) and
      hydrocortisone (10 nM)), FFA (oleic and linoleic acid, 100 and 400 microM each),
      IGF-I (0.5-50 nM), and insulin (0.5-50 nM) on GH release and GH, GHRH-receptor
      (GHRH-R) and ghrelin-receptor (GHS-R) mRNA levels, in primary pituitary cell
      cultures of baboons (Papio anubis) after 24 h treatment. A commercial ELISA kit
      was used to determine the amount of GH released into the media, while
      quantitative real-time reverse transcription-PCR was used to determine mRNA
      levels. To design species-specific primers for baboon GH, GHRH-R, GHS-R, insulin
      receptor (INSR), IGF-I receptor (IGF-IR), pituitary-specific transcription factor
      1 (Pit-1), and cyclophilin A (used as a housekeeping gene) cDNA, sequence data
      for each baboon transcript were obtained and this data were submitted to Genbank.
      Glucocorticoids, FFA, insulin and IGF-I treatment did not significantly alter the
      expression of Pit-1, a transcription factor essential for normal somatotrope
      development and function. However, as previously reported in the rat,
      glucocorticoids increased, while FFA, IGF-I and insulin decreased GH release in
      baboon pituitary cell cultures, where changes in GH release were reflected by
      comparable changes in GH mRNA levels. In addition, glucocorticoids increased,
      while FFA, IGF-I and insulin decreased the expression of the GH stimulatory
      receptors, GHRH-R and GHS-R, without significantly altering cyclophilin A mRNA
      levels. A role of insulin/INSR pathway, independent of IGF-I, in regulating
      pituitary function is supported by the fact that (1) IGF-I and insulin
      significantly suppressed somatotrope function at doses (0.5 and 5 nM
      respectively) not anticipated to activate their respective receptors, and (2) the
      baboon pituitary expresses INSR mRNA at levels comparable to or greater than that
      of tissues commonly considered as insulin sensitive (i.e. liver, skeletal muscle,
      and fat). Taken together, these results demonstrate that metabolic factors can
      directly modulate primate somatotrope function through regulating GH synthesis
      and release, as well as mediating the expression of receptors important in
      central (GHRH) and systemic (ghrelin) regulation of GH secretion.

PMID- 16901922
TI  - Differential expression of the thyrostimulin subunits, glycoprotein alpha2 and
      beta5 in the rat pituitary.
AB  - Two glycoprotein hormone subunits, (glycoprotein hormone alpha2-subunit GPA2) and
      (glycoprotein hormone beta5-subunit GPB5) have been recently discovered which,
      when expressed in vitro, heterodimerize to form a new hormone called
      thyrostimulin. Thyrostimulin activates the thyroid-stimulating hormone receptor
      (TSHR) and has thyrotropic activity. Immunological studies have indicated that
      both subunits co-localize in pituitary cells. To explore the function of
      thyrostimulin in the rat, we have cloned rat GPA2 and GPB5, reconstituted the
      heterodimers in vitro, and confirmed that rat thyrostimulin activates TSHR with
      an affinity similar to that of TSH. In situ hybridization of the pituitary showed
      that while GPA2 is expressed in the anterior lobe, GPB5 is not detected in any of
      the lobes. A quantitative analysis showed that the co-localization of GPA2 and
      GPB5 is restricted in the rat to the eye and the testis. We found that GPB5 can
      be detected in the pituitary by quantitative-PCR, but at extremely low levels,
      2000-fold lower than TSH beta-subunit (GPBtsh). Furthermore, the levels of GPB5
      remain constant during the estrus cycle, while those of GPA2 vary. Finally, we
      found that none of the thyrostimulin subunits was induced by TRH in pituitary
      cell culture. These data point at the thyrostimulin system as being functionally
      different to the TSH system.

PMID- 16901923
TI  - Characterization of ghrelin receptor activity in a rat pituitary cell line RC
      4B/C.
AB  - Ghrelin, a 28 amino acid, octanoylated peptide, is an endogenous ligand for the
      growth hormone secretagogue receptor (GHS-R). In addition to various endocrine
      functions, including stimulation of GH release, ghrelin has been characterized as
      an important regulator of energy homeostasis. Ghrelin administration has been
      shown to increase adiposity in rodents and stimulate food intake in humans.
      Studies suggest that these orexigenic effects are mediated primarily through GHS
      R expression in hypothalamic and pituitary neuronal pathways. In this context,
      GHS-R has been recognized as a potential target for the treatment of GH
      deficiency and body weight disorders. Cell lines provide convenient in vitro
      systems to identify and characterize potential pharmacophores and to analyze GHS
      R functional activity. While recombinant cell lines that overexpress GHS-R have
      served as effective research tools for these studies, such cell lines may differ
      in signaling response to ghrelin compared with hypothalamic or pituitary cells
      expressing GHS-R. We show here that a cell line derived from a rat anterior
      pituitary adenoma, RC-4B/C, expresses endogenous GHS-R as judged by reverse
      transcriptase-PCR. In a Ca(2+)mobilization assay, RC-4B/C cells demonstrate a
      dose-dependent increase in intracellular [Ca(2+)] on stimulation with rat ghrelin
      and a related peptide agonist, hexarelin (EC(50), 1.0 nM and 1.7 nM
      respectively), but are unresponsive to treatment with inactive des-octanoyl rat
      ghrelin. A subclone, RC-4B/C.40, with a more robust and stable ghrelin response,
      was isolated from the parental population of cells to allow further analysis of
      GHS-R signal transduction. Using pertussis toxin and the phospholipase C
      inhibitor U-73122, we show that ghrelin signals through the Gq pathway in the RC
      4B/C.40 cells. We also demonstrate that the ghrelin-induced rise of intracellular
      [Ca(2+)] in RC-4B/C.40 cells involves initial Ca(2+)release from intracellular
      stores followed by a sustained elevation that occurs via influx of extracellular
      Ca(2+) through ion channels. In addition, unlike observations reported in
      recombinant cell systems, the RC-4B/C.40 cells do not exhibit a high level of GHS
      R constitutive activity as determined in a phosphatidylinositol hydrolysis assay.
      Overall, the data presented here suggest that the RC-4B/C parental and RC-4B/C.40
      cells provide novel in vitro systems for the characterization of GHS-R
      pharmacophores and ghrelin signaling.

PMID- 16901924
TI  - A novel technique for temporally regulated cell type-specific Cre expression and
      recombination in the pituitary gonadotroph.
AB  - Inducing tissue-specific genetic alterations under temporal control allows for
      the analysis of gene function in particular cell types at specified points in
      time. We have generated a system for tetracycline-controlled expression of Cre
      recombinase in mice using the unique CreTeR vector. The gonadotroph-specific
      bovine alpha-subunit (Balpha) promoter fragment was subcloned into the CreTeR
      vector, creating a technique for highly regulated expression of Cre recombinase
      exclusively in pituitary gonadotrophs. Control of Cre recombinase in the CreTeR
      vector was demonstrated in LbetaT2 pituitary cell lines, where Cre protein was
      detected in cells treated with doxycycline, but not in untreated cells. In
      transgenic mice, Cre was expressed in pituitary gonadotrophs of mice treated with
      doxycycline, but not in non-pituitary tissues or in transgenic mice not treated
      with doxycycline. We demonstrated Cre expression in the gonadotroph by
      immunostaining showing co-localization of Cre recombinase with the beta-subunit
      of LH (LH-beta). Furthermore, by crossing Balpha/CreTeR with R26R mice, we were
      able to demonstrate functional recombination within pituitary gonadotrophs,
      detected by lacZ expression. The Balpha/CreTeR mice described here can be used to
      study the function of virtually any gene in the gonadotroph; in particular, this
      will be useful in studying genes, which may have distinct roles in development
      and in the adult.

PMID- 16901925
TI  - A novel mutation in the steroidogenic acute regulatory protein gene promoter
      leading to reduced promoter activity.
AB  - We have identified a novel cytosine/thymidine polymorphism of the human
      steroidogenic acute regulatory (StAR) gene promoter located 3 bp downstream of
      the steroidogenic factor-1 (SF-1)-binding site and 9 bp upstream of the TATA box
      (ATTTAAG). Carriers of this mutation have a high prevalence of primary
      aldosteronism. In transfection experiments, basal StAR promoter activity was
      unaltered by the mutation in murine Y-1 cells and human H295R cells. In Y-1
      cells, forskolin (25 microM, 6 h) significantly increased wild-type promoter
      activity to 230+/-33% (P<0.05, n=4). In contrast, forskolin increased mutated
      promoter activity only to 150+/-27%, with a significant 35% reduction compared to
      wild type (P<0.05, n=3). In H295R cells, angiotensin II (AngII; 10 nM) increased
      wild-type StAR promoter activity to 265+/-22% (P<0.01, n=3), while mutated StAR
      promoter activity in response to AngII only reached 180+/-29% of controls (P<
      0.01, n=3). Gel mobility shift assays show the formation of two additional
      complexes with the mutated promoter: one with the transcription repressor DAX-1
      and another with a yet unidentified factor, which strongly binds the SF-1
      response element. Thus, this novel mutation in the human StAR promoter is
      critically involved in the regulation of StAR gene expression and is associated
      with reduced promoter activity, a finding relevant for adrenal steroid response
      to physiological stimulators.

PMID- 16901927
TI  - Genetic association studies of the FOXP3 gene in Graves' disease and autoimmune
      Addison's disease in the United Kingdom population.
AB  - Regulatory T lymphocytes play a crucial role in modulating potentially self
      reactive clones, and dysfunction of this cell type contributes to autoimmune
      disease. FOXP3 is a critical determinant of CD(4+)CD(25+)T regulatory (T(reg))
      cell development and function. The aim of this study was to investigate whether
      genetic polymorphisms at the FOXP3 locus predispose to autoimmune
      endocrinopathies. Five single nucleotide polymorphisms (SNPs) and two
      microsatellite polymorphisms were genotyped in our Caucasian cohorts of 633
      unrelated Graves' disease (GD) subjects, 104 autoimmune Addison's disease (AAD)
      subjects and 528 healthy controls. SNP genotyping was performed by either
      restriction enzyme digestion or by primer-extension-MALDI-TOF (matrix-assisted
      laser desorption/ionisation time-of-flight) assay. Microsatellites were analysed
      using fluorescent PCR. Case-control analysis was performed using chi(2) testing
      on contingency tables for allele frequency. Haplotype analysis was performed
      using the UNPHASED package. No evidence for disease association was found with
      any of the seven polymorphisms in either of the GD or AAD subjects as compared
      with controls (P = 0.26-0.94). Haplotype analysis found a weak evidence for the
      association of a minor haplotype with GD; this was not significant when corrected
      for multiple testing. This study has found no robust evidence that FOXP3 gene
      polymorphism contributes to the susceptibility to GD or AAD in the UK population.

PMID- 16901926
TI  - cAMP-independent signaling regulates steroidogenesis in mouse Leydig cells in the
      absence of StAR phosphorylation.
AB  - In the regulation of steroid biosynthesis, a process mediated by the
      steroidogenic acute regulatory (StAR) protein, both cAMP-dependent and 
      independent pathways are involved. While the cAMP-dependent regulatory events
      represent, by far, the most robust increase in steroid synthesis and are well
      established, the knowledge regarding cAMP-independent mechanisms is lacking. The
      present investigation was designed to elucidate the potential involvement of the
      latter in regulating StAR expression and steroidogenesis in mouse Leydig tumor
      cells (mLTC-1 cells). Treatment of mLTC-1 cells with a number of factors
      including insulin-like growth factor-I (IGF-I), epidermal growth factor (EGF),
      fibroblast growth factor, transforming growth factor (TGF)alpha, interleukin-1
      (IL-1), and colony-stimulating factor-1, increased the levels of StAR mRNA, StAR
      protein, and progesterone to varying degrees and utilized signaling pathways that
      are not associated with elevations in intracellular cAMP levels. Importantly,
      phosphorylation of StAR in response to these stimuli was undetectable, which is
      in marked contrast to observations with human chorionic gonadotropin (hCG),
      indicating factors that do not alter intracellular cAMP, regulate the steroid
      biosynthesis in a StAR phosphorylation-independent manner. In addition, the roles
      for factors involved in cross-talk between the protein kinase pathways, PKA and
      PKC, were demonstrated. Further characterization of signaling by one such cAMP
      independent factor, TGFalpha, demonstrated that the mechanism, whereby it
      increased StAR expression and steroid synthesis, was dependent on de novo protein
      synthesis and mediated via activation of the EGF receptor. TGFalpha was also able
      to augment hCG-stimulated cAMP synthesis, StAR protein and StAR phosphorylation,
      and influence hCG binding and LH receptor mRNA expression. Furthermore, TGFalpha
      increased phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2)
      and cAMP-response element-binding protein (CREB), processes inhibited by the
      mitogen-activated protein kinase/ERK inhibitor U0126 and by expression of non
      phosphorylatable CREB-M1 respectively. Inhibition of ERK activity enhanced
      TGFalpha-mediated StAR protein expression (but not its phosphorylation) and
      decreased progesterone synthesis, events correlated with the expression of dosage
      sensitive sex reversal, adrenal hypoplasia congenita, critical region on the X
      chromosome, gene 1 (DAX-1) and scavenger receptor class B type 1 (SR-B1).
      Collectively, these findings demonstrate that, in mouse Leydig cells, cAMP
      independent signaling events regulate steroidogenesis in a StAR phosphorylation
      independent manner.

PMID- 16901928
TI  - Estrogen receptor-related receptors in the killifish Fundulus heteroclitus:
      diversity, expression, and estrogen responsiveness.
AB  - The estrogen receptor-related receptors (ERRs) are a group of nuclear receptors
      that were originally identified on the basis of sequence similarity to the
      estrogen receptors. The three mammalian ERR genes have been implicated in diverse
      physiological processes ranging from placental development to maintenance of bone
      density, but the diversity, function, and regulation of ERRs in non-mammalian
      species are not well understood. In this study, we report the cloning of four ERR
      cDNAs from the Atlantic killifish, Fundulus heteroclitus, along with adult tissue
      expression and estrogen responsiveness. Phylogenetic analysis indicates that F.
      heteroclitus (Fh)ERRalpha is an ortholog of the single ERRalpha identified in
      mammals, pufferfish, and zebrafish. FhERRbetaa and FhERRbetab are co-orthologs of
      the mammalian ERRbeta. Phylogenetic placement of the fourth killifish ERR gene,
      tentatively identified as FhERRgammab, is less clear. The four ERRs showed
      distinct, partially overlapping mRNA expression patterns in adult tissues.
      FhERRalpha was broadly expressed. FhERRbetaa was expressed at apparently low
      levels in eye, brain, and ovary. FhERRbetab was expressed more broadly in liver,
      gonad, eye, brain, and kidney. FhERRgammab was expressed in multiple tissues
      including gill, heart, kidney, and eye. Distinct expression patterns of
      FhERRbetaa and FhERRbetab are consistent with subfunctionalization of the ERRbeta
      paralogs. Induction of ERRalpha mRNA by exogenous estrogen exposure has been
      reported in some mammalian tissues. In adult male killifish, ERR expression did
      not significantly change following estradiol injection, but showed a trend toward
      a slight induction (three- to five-fold) of ERRalpha expression in heart. In a
      second, more targeted experiment, expression of ERRalpha in adult female
      killifish was downregulated 2.5-fold in the heart following estradiol injection.
      In summary, our results indicate that killifish contain additional ERR genes
      relative to mammals, including ERRbeta paralogs. In addition, regulation of
      ERRalpha expression in killifish apparently differs from regulation in mammals.
      Together, these features may facilitate determination of both conserved and
      specialized ERR gene functions.

PMID- 16901929
TI  - Multiple molecular effect pathways of an environmental oestrogen in fish.
AB  - Complex interrelationships in the signalling of oestrogenic effects mean that
      environmental oestrogens present in the aquatic environment have the potential to
      disrupt physiological function in fish in a more complex manner than portrayed in
      the present literature. Taking a broader approach to investigate the possible
      effect pathways and the likely consequences of environmental oestrogen exposure
      in fish, the effects of 17beta-oestradiol (E(2)) were studied on the expression
      of a suite of genes which interact to mediate growth, development and thyroid and
      interrenal function (growth hormone GH (gh), GH receptor (ghr ), insulin-like
      growth factor (IGF-I) (igf1), IGF-I receptor (igf1r ), thyroid hormone receptors
      alpha (thra) and -beta (thrb) and glucocorticoid receptor (gr )) together with
      the expression analyses of sex-steroid receptors and ten other genes centrally
      involved in sexual development and reproduction in fathead minnow (fhm;
      Pimephales promelas). Exposure of adult fhm to 35 ng E(2)/l for 14 days induced
      classic oestrogen biomarker responses (hepatic oestrogen receptor 1 and plasma
      vitellogenin), and impacted on the reproductive axis, feminising "male"
      steroidogenic enzyme expression profiles and suppressing genes involved in testis
      differentiation. However, E(2) also triggered a cascade of responses for gh, ghr,
      igf1, igf1r, thra, thrb and gr in the pituitary, brain, liver, gonad and gill,
      with potential consequences for the functioning of many physiological processes,
      not just reproduction. Molecular responses to E(2) were complex, with most genes
      showing differential responses between tissues and sexes. For example, igf1
      expression increased in brain but decreased in gill on exposure to E(2), and
      responded in an opposite way in males compared with females in liver, gonad and
      pituitary. These findings demonstrate the importance of developing a deeper
      understanding of the endocrine interactions for unravelling the mechanisms of
      environmental oestrogen action and predicting the likely health consequences.

PMID- 16901930
TI  - Identification and cloning of a glycoprotein hormone receptor from sea lamprey,
      Petromyzon marinus.
AB  - A full-length transcript encoding a functional lamprey glycoprotein hormone
      receptor I (lGpH-R I, GenBank AY750688) was cloned from the testes of the sea
      lamprey, Petromyzon marinus, using the GpH-R protein fingerprint GLYCHORMONER
      from the PRINTS database. The present study is the first to identify a GpH-R
      transcript in an agnathan, which is one of the only two representatives of the
      oldest lineage of vertebrates. The 719-amino acid full-length cDNA encoding lGpH
      R I is highly similar and is likely a homolog of the vertebrate GpH-Rs (including
      LH, FSH, and TSH receptors). The key motifs, sequence comparisons, and
      characteristics of the identified GpH-R reveal a mosaic of features common to all
      other classes of GpH-Rs in vertebrates. The lGpH-R I was shown to activate the
      cAMP signaling system using human chorionic gonadotropin in transiently
      transfected COS-7 cells. The highest expression of the receptor transcript was
      demonstrated in the testes using reverse transcriptase-PCR. Lower levels of the
      receptor transcript were also detected in brain, heart, intestine, kidney, liver,
      muscle, and thyroid. The high expression of lGpH-R I in the testis and the high
      similarity with gnathostome gonadotropin hormone receptors suggest that lGpH-R I
      functions as a receptor for lamprey gonadotropin hormones. We hypothesize from
      these data that there is lower specificity of gonadotropin and its receptor in
      agnathans and that during co-evolution of the ligand and its receptor in
      gnathostomes, there were increased specificities of interactions between each GpH
      (TSH, LH, and FSH) and its receptor.

PMID- 16901931
TI  - Global analysis of differential luminal epithelial gene expression at mouse
      implantation sites.
AB  - Although implantation types differ between species, the interaction between
      blastocyst trophectoderm and apical surface of the uterine epithelium is a common
      event during the implantation process. In this study, uterine luminal epithelium
      at implantation and inter-implantation sites was isolated by enzymatic digestion
      and used for microarray analysis. In a mouse microarray containing 12 345
      unigenes, we found 136 genes upregulated more than twofold at the implantation
      site, while 223 genes were downregulated by at least twofold. Reverse
      transcription-PCR was used to verify the differential expression of seven
      upregulated and six downregulated genes chosen randomly from our microarray
      analysis, and the expression trends were similar. The differential expression
      patterns of eight upregulated genes were verified by in situ hybridization.
      Compared with the inter-implantation site on day 5 of pregnancy and the uterus on
      day 5 of pseudopregnancy, protease, serine, 12 neurotrypsin, endothelin-1, gamma
      glutamyl hydrolase, Ras homolog gene family, member U, T-cell immunoglobulin, and
      mucin domain containing 2, proline-serine-threonine phosphatase-interacting
      protein 2, 3-monooxgenase/tryptophan 5-monooxgenase activation protein, gamma
      polypeptide, and cysteine-rich protein 61 (Cyr61) were upregulated in the luminal
      epithelium at implantation site on day 5 of pregnancy. These genes may be related
      to embryo apposition and adhesion during embryo implantation. Cyr61, a gene
      upregulated at the implantation site, was chosen to examine its expression and
      regulation during the periimplantation period by in situ hybridization. Cyr61
      mRNA was specifically localized in the luminal epithelium surrounding the
      implanting blastocyst at day 4 midnight and on day 5 of pregnancy, and in the
      activated uterus, but not expressed in inter-implantation sites and under delayed
      implantation, suggesting a role for Cyr61 in mediating embryonic-uterine dialog
      during embryo attachment. Our data could be a valuable source for future study on
      embryo implantation.

PMID- 16901932
TI  - Differential interaction of RU486 with the progesterone and glucocorticoid
      receptors.
AB  - Steroid hormone receptor antagonists are widely used in clinical medicine, but
      their use is often complicated by the lack of receptor specificity to presently
      available drugs. We previously demonstrated an important role of a widely
      conserved helix 3 (H3)-helix 5 (H5) interaction in determining the sensitivity
      and specificity of steroid hormone receptors to receptor agonists. Intriguingly,
      the same H3 residues also play a crucial role in receptor antagonism; mutation of
      these residues alters the response of these receptors to antagonists. Given the
      close interaction of H3 and H5 residues at this site, we asked whether H5
      residues might also play a role in the sensitivity of these receptors to
      antagonists. We demonstrate here that modification of H5 residues produces marked
      changes in the sensitivities of the glucocorticoid and progesterone receptor (PR)
      to RU486 antagonism. Moreover, while we confirm previous reports that alteration
      of the H3 residue, Gly 722 prevents RU486-mediated inhibition of the PR, we show
      that the corresponding substitution in the glucocorticoid receptor does not
      inhibit RU486-mediated receptor antagonism. Taken together, our data support the
      notion that RU486 binds differently to these two receptors, providing a potential
      target for the design of more specific antiglucocorticoid and antiprogestin
      drugs.

PMID- 16901933
TI  - Metformin reduces lipolysis in primary rat adipocytes stimulated by tumor
      necrosis factor-alpha or isoproterenol.
AB  - In patients with type 2 non-insulin-dependent diabetes mellitus (NIDDM), the
      biguanide, metformin, exerts its antihyperglycemic effect by improving insulin
      sensitivity, which is associated with decreased level of circulating free fatty
      acids (FFA). The flux of FFA and glycerol from adipose tissue to the blood stream
      primarily depends on the lipolysis of triacylglycerols in the adipocytes.
      Adipocyte lipolysis is physiologically stimulated by catecholamine hormones.
      Tumor necrosis factor-alpha (TNF-alpha), a cytokine largely expressed in adipose
      tissue, stimulates chronic lipolysis, which may be associated with increased
      systemic FFA and insulin resistance in obesity and NIDDM. In this study, we
      examined the role of metformin in inhibiting lipolytic action upon various
      lipolytic stimulations in primary rat adipocytes. Treatment with metformin
      attenuated TNF-alpha-mediated lipolysis by suppressing phosphorylation of
      extracellular signal-related kinase 1/2 and reversing the downregulation of
      perilipin protein in TNF-alpha-stimulated adipocytes. The acute lipolytic
      response to adrenergic stimulation of isoproterenol was also restricted by
      metformin. A high concentration of glucose in the adipocyte culture promoted the
      basal rate of glycerol release and significantly enhanced the lipolytic action
      stimulated by either TNF-alpha or isoproterenol. Metformin not only inhibits the
      basal lipolysis simulated by high glucose, but also suppresses the high glucose
      enhanced lipolysis response to TNF-alpha or isoproterenol. The antilipolytic
      action in adipocytes could be the mechanism by which cellular action by metformin
      reduces systemic FFA concentration and thus improves insulin sensitivity in obese
      patients and the hyperglycemic conditions of NIDDM.

PMID- 16901934
TI  - Transcriptional regulation of human and murine 17beta-hydroxysteroid
      dehydrogenase type-7 confers its participation in cholesterol biosynthesis.
AB  - In both humans and mice, 17beta-hydroxysteroid dehydrogenase type-7 (HSD17B7) was
      described as possessing dual enzymatic functionality. The enzyme was first shown
      to be able to convert estrone to estradiol in vitro. Later involvement of this
      enzyme in postsqualene cholesterol biosynthesis was postulated (conversion of
      zymosterone to zymosterol) and could be proven in vitro. In this work, we
      performed a detailed analysis of the transcriptional regulation of both the human
      and murine genes. Despite relatively low sequence similarity, both promoters
      contain similar contexts of transcription factor-binding sites. The participation
      of these sites in transcriptional regulation of HSD17B7 was proven by electro
      mobility shift assay and site-directed mutagenesis of the corresponding binding
      sites. We describe novel involvement of vitamin D receptor/retinoid X receptor
      and provide new information on the regulation of HSD17B7 expression by sterol
      regulatory element-binding protein and hepatocyte nuclear factor 4, the latter
      known from other genes of cholesterogenic enzymes. The results of our study
      provide unequivocal evidence for a role of HSD17B7 in cholesterol biosynthesis.

PMID- 16901935
TI  - Significant sequence similarities in promoters and precursors of Arabidopsis
      thaliana non-conserved microRNAs.
AB  - Some plant microRNAs have been shown to be de novo generated by inverted
      duplication from their target genes. Subsequent duplication events potentially
      generate multigene microRNA families. Within this article we provide supportive
      evidence for the inverted duplication model of plant microRNA evolution. First,
      we report that the precursors of four Arabidopsis thaliana microRNA families,
      miR157, miR158, miR405 and miR447 share nearly identical nucleotide sequences
      throughout the whole miRNA precursor between the family members. The extent and
      degree of sequence conservation is suggestive of recent evolutionary duplication
      events. Furthermore we found that sequence similarities are not restricted to the
      transcribed part but extend into the promoter regions. Thus the duplication event
      most probably included the promoter regions as well. Conserved elements in
      upstream regions of miR163 and its targets were also detected. This implies that
      the inverted duplication of target genes, at least in certain cases, had included
      the promoters of the target genes. Sequence conservation within promoters of
      miRNA families as well as between miRNA and its potential progenitor gene can be
      exploited for understanding the regulation of microRNA genes.

PMID- 16901936
TI  - Potentiation of transient receptor potential V1 functions by the activation of
      metabotropic 5-HT receptors in rat primary sensory neurons.
AB  - 5-Hydroxytryptamine (5-HT) is one of the major chemical mediators released in
      injured and inflamed tissue and is capable of inducing hyperalgesia in vivo.
      However, the cellular mechanisms of 5-HT-induced hyperalgesia remain unclear.
      Transient receptor potential V1 (TRPV1) plays a pivotal role in nociceptive
      receptors. In the present study, we determined whether 5-HT changes TRPV1
      functions in cultured dorsal root ganglion (DRG) neurons isolated from neonatal
      rats, using Ca(2+) imaging and whole-cell patch-clamp techniques. In more than
      70% of DRG neurons, 5-HT potentiated the increases of [Ca(2+)](i) induced by
      capsaicin, protons and noxious heat. Capsaicin-induced current and depolarizing
      responses, and proton-induced currents were also augmented by 5-HT. RT-PCR
      analysis revealed the expression of 5-HT(2A) and 5-HT(7) receptors in rat DRG
      neurons. Agonists for 5-HT(2A) and 5-HT(7) receptors mimicked the potentiating
      effect of 5-HT, and their antagonists decreased it. In DRG ipsilateral to the
      complete Freund's adjuvant-injected inflammation side, expression levels of 5
      HT(2A) and 5-HT(7) mRNAs increased, and the potentiating effect of 5-HT was more
      prominent than in the contralateral control side. These results suggest that the
      PKC- and PKA-mediated signalling pathways are involved in the potentiating effect
      of 5-HT on TRPV1 functions through the activation of 5-HT(2A) and 5-HT(7)
      receptors, respectively. Under inflammatory conditions, the increases of the
      biosynthesis of these 5-HT receptors may lead to further potentiation of TRPV1
      functions, resulting in the generation of inflammatory hyperalgesia in vivo.

PMID- 16901937
TI  - Hypoxia-sensing properties of the newborn rat ventral medullary surface in vitro.
AB  - The ventral medullary surface (VMS) is a region known to exert a respiratory
      stimulant effect during hypercapnia. Several studies have suggested its
      involvement in the central inhibition of respiratory rhythm caused by hypoxia. We
      studied brainstem-spinal cord preparations isolated from newborn rats transiently
      superfused with a very low O(2) medium, causing reversible respiratory
      depression, to characterize the participation of the VMS in hypoxic respiratory
      adaptation. In the presence of 0.8 mM Ca(2+), very low O(2) medium induced an
      increase in c-fos expression throughout the VMS. The reduction of synaptic
      transmission and blockade of the respiratory drive by 0.2 mM Ca(2+)-1.6 mM Mg(2+)
      abolished c-fos expression in the medial VMS (at the lateral edge of the
      pyramidal tract) but not in the perifacial retrotrapezoid nucleus/parafacial
      respiratory group (RTN/pFRG) VMS, suggesting the existence of perifacial RTN/pFRG
      hypoxia-sensing neurons. In the presence of Ca(2+) (0.8 mM), lesioning
      experiments suggested a physiological difference in perifacial RTN/pFRG VMS
      between the lateral VMS (beneath the ventrolateral part of the facial nucleus)
      and the middle VMS (beneath the ventromedial part of the facial nucleus), at
      least in newborn rats. The lateral VMS lesion, corresponding principally to the
      most rostral part of the pFRG, produced hypoxia-induced stimulation, whereas the
      middle VMS lesion, corresponding to the main part of the RTN, abolished hypoxic
      excitation. This may involve relay via the medial VMS, which is thought to be the
      parapyramidal group.

PMID- 16901938
TI  - Muscle fatigue and reactive oxygen species.

PMID- 16901939
TI  - Nicotinic modulation of network and synaptic transmission in the immature
      hippocampus investigated with genetically modified mice.
AB  - The hippocampus, a key structure in learning and memory processes, receives a
      powerful cholinergic innervation from the septum and contains nicotinic
      acetylcholine receptors (nAChRs). Early in postnatal development, activation of
      nAChRs by nicotine or endogenous acetylcholine contributes to enhance synaptic
      signalling. Here, the patch-clamp technique was used to assess the contribution
      of alpha7 and beta2-containing (alpha7* and beta2*) nAChRs to nicotine-elicited
      modulation of GABAergic and glutamatergic activity at the network and single-cell
      level in the immature hippocampus of wild-type (WT), alpha7-/- and beta2-/- mice.
      We found that alpha7* and beta2* nAChRs were sufficient to modulate nicotine
      induced increase in frequency of spontaneously occurring giant depolarizing
      potentials (GDPs), which are generated at the network level by the synergistic
      action of glutamate and depolarizing GABA, and thought to play a crucial role in
      neuronal wiring. However, alpha7* but not beta2* receptors were essential in
      nicotine-induced increase of interictal discharge frequency recorded after
      postnatal day 3 in the presence of bicuculline, when GABA shifted from the
      depolarizing to the hyperpolarizing direction. To correlate these observations
      with nicotine-elicited changes in synaptic transmission, we recorded spontaneous
      GABAergic and glutamatergic postsynaptic currents in pyramidal cells and
      interneurons localized in stratum oriens, stratum pyramidale and stratum
      radiatum, in slices obtained from WT and knock-out animals. We found that early
      in postnatal life alpha7* and beta2* nAChRs exert a fine regional modulation of
      GABAergic and glutamatergic transmission that underlies nicotine-elicited changes
      in network synchronization.

PMID- 16901940
TI  - pH dependence and inhibition by extracellular calcium of proton currents via
      plasmalemmal vacuolar-type H+-ATPase in murine osteoclasts.
AB  - The vacuolar-type H(+)-ATPase (V-ATPase) in the plasma membrane of a variety of
      cells serves as an acid-secreting pathway, and its activity is closely related to
      cellular functions. Massive proton secretion often leads to electrolyte
      disturbances in the vicinity of the cell and may in turn affect the activity of
      the V-ATPase. We characterized, for the first time, the proton currents mediated
      by plasmalemmal V-ATPase in murine osteoclast-like cells and investigated its
      activity over a wide range of pH gradients across the membrane (DeltapH =
      extracellular pH - intracellular pH). The V-ATPase currents were identified as
      outward H(+) currents and were dependent on ATP and sensitive to the inhibitors
      bafilomycin A(1) and N,N'-dicyclohexylcarbodiimide. Although H(+) was transported
      uphill, the electrochemical gradient for H(+) affected the current. The currents
      were increased by elevating DeltapH and depolarization, and were reduced by
      lowering DeltapH and hyperpolarization. Elevation of extracellular Ca(2+) (5-40
      mm) diminished the currents in a dose-dependent manner and made the voltage
      dependence more marked. Extracellular Mg(2+) mimicked the inhibition. With 40 mm
      Ca(2+), the currents decreased to < 40% at 0 mV and to < 10% at about -80 mV.
      Increases in the intracellular Ca(2+) (0.5-5 microm) did not affect the current.
      The data suggest that acid secretion through the plasmalemmal V-ATPase is
      regulated by a combination of the pH gradient, the membrane potential and the
      extracellular divalent cations. In osteoclasts, the activity-dependent
      accumulation of acids and Ca(2+) in the closed extracellular compartment might
      serve as negative feedback signals for regulating the V-ATPase.

PMID- 16901941
TI  - Deafness in LIMP2-deficient mice due to early loss of the potassium channel
      KCNQ1/KCNE1 in marginal cells of the stria vascularis.
AB  - Our previous studies revealed a critical role of the lysosomal membrane protein
      LIMP2 in the regulation of membrane transport processes in the endocytic pathway.
      Here we show that LIMP2-deficient mice display a progressive high-frequency
      hearing loss and decreased otoacoustic emissions as early as 4 weeks of age. In
      temporal overlap to hearing impairment, fluorescence immunohistochemical studies
      revealed that the potassium channel KCNQ1 and its beta-subunit KCNE1 were almost
      completely lost in the luminal part of marginal cells in the stria vascularis,
      affecting first higher and later also lower frequency processing cochlear turns.
      Concomitant with this, the expression of megalin, a multiligand endocytic
      receptor, was reduced in luminal surfaces of marginal cells within the stria
      vascularis. KCNQ1/KCNE1 and megalin were also lost in the dark cells of the
      vestibular system. Although LIMP2 is normally expressed in all cells of the stria
      vascularis, in the organ of Corti and cochlear neurons, the lack of LIMP2
      preferentially caused a loss of KCNQ1/KCNE1 and megalin, and structural changes
      were only seen months later, indicating that these proteins are highly sensitive
      to disturbances in the lysosomal pathway. The spatio-temporal correlation of the
      loss of KCNQ1/KCNE1 surface expression and loss of hearing thresholds supports
      the notion that the decline of functional KCNQ1/KCNE1 is likely to be the primary
      cause of the hearing loss. Our findings suggest an important role for LIMP2 in
      the control of the localization and the level of apically expressed membrane
      proteins such as KCNQ1, KCNE1 and megalin in the stria vascularis.

PMID- 16901942
TI  - What is the hair cell transduction channel?
AB  - In contrast to nearly all other sensory systems, the mechanically sensitive ion
      channel carrying the receptor current into hair cells of the inner ear has not
      been identified in molecular terms. A number of candidates from at least two
      different ion channel families have been considered: these include the epithelial
      sodium channel (ENaC) and acid-sensing ion channel (ASIC) members of the DEG/ENaC
      superfamily of amiloride-sensitive sodium channels, as well as the TRP channels
      TRPN1, TRPV4, TRPML3 and TRPA1. For each, initial supportive results were
      followed by further studies that cast doubts on their involvement. No promising
      candidates have recently emerged, but the TRP family continues to be attractive
      in general.

PMID- 16901943
TI  - Monocarboxylate transporter 1 (MCT1) plays a direct role in short-chain fatty
      acids absorption in caprine rumen.
AB  - Despite the importance of short-chain fatty acids (SCFA) in maintaining the
      ruminant physiology, the mechanism of SCFA absorption is still not fully studied.
      The goal of this study was to elucidate the possible involvement of
      monocarboxylate transporter 1 (MCT1) in the mechanism of SCFA transport in the
      caprine rumen, and to delineate the precise cellular localization and the level
      of MCT1 protein along the entire caprine gastrointestinal tract. RT-PCR revealed
      the presence of mRNA encoding for MCT1 in all regions of the caprine
      gastrointestinal tract. Quantitative Western blot analysis showed that the level
      of MCT1 protein was in the order of rumen >/= reticulum > omasum > caecum >
      proximal colon > distal colon > abomasum > small intestine. Immunohistochemistry
      and immunofluorescence confocal analyses revealed widespread immunoreactive
      positivities for MCT1 in the caprine stomach and large intestine. Amongst the
      stratified squamous epithelial cells of the forestomach, MCT1 was predominantly
      expressed on the cell boundaries of the stratum basale and stratum spinosum.
      Double-immunofluorescence confocal laser-scanning microscopy confirmed the co
      localization of MCT1 with its ancillary protein, CD147 in the caprine
      gastrointestinal tract. In vivo and in vitro functional studies, under the
      influence of the MCT1 inhibitors, p-chloromercuribenzoate (pCMB) and p
      chloromercuribenzoic acid (pCMBA), demonstrated significant inhibitory effect on
      acetate and propionate transport in the rumen. This study provides evidence, for
      the first time in ruminants, that MCT1 has a direct role in the transepithelial
      transport and efflux of the SCFA across the stratum spinosum and stratum basale
      of the forestomach toward the blood side.

PMID- 16901944
TI  - ON direction-selective ganglion cells in the mouse retina.
AB  - Two types of ganglion cells (RGCs) compute motion direction in the retina: the ON
      OFF direction-selective ganglion cells (DSGCs) and the ON DSGCs. The ON DSGCs are
      much less studied mostly due to the low encounter rate. In this study, we
      investigated the physiology, dendritic morphology and synaptic inputs of the ON
      DSGCs in the mouse retina. When a visual stimulus moved back and forth in the
      preferred-null axis, we found that the ON DSGCs exhibited a larger EPSC when the
      visual stimulus moved in the preferred direction and a larger IPSC in the
      opposite, or null direction, similar to what has been found in ON-OFF DSGCs. This
      similar synaptic input pattern is in contrast to other well-known differences,
      namely: profile of velocity sensitivity, distribution of preferred directions,
      and different central projection of the axons. Immunohistochemical staining
      showed that the dendrites of ON DSGCs exhibited tight cofasciculation with the
      cholinergic plexus. These findings suggest that cholinergic amacrine cells may
      play an important role in generating direction selectivity in the ON DSGCs, and
      that the mechanism for coding motion direction is probably similar for the two
      types of DSGCs in the retina.

PMID- 16901945
TI  - Central chemoreceptors and sympathetic vasomotor outflow.
AB  - The present study explores how elevations in brain P(CO(2)) increase the
      sympathetic nerve discharge (SND). SND, phrenic nerve discharge (PND) and
      putative sympathoexcitatory vasomotor neurons of the rostral ventrolateral
      medulla (RVLM) were recorded in anaesthetized sino-aortic denervated and
      vagotomized rats. Hypercapnia (end-expiratory CO(2) from 5% to 10%) increased SND
      (97 +/- 6%) and the activity of RVLM neurons (67 +/- 4%). Injection of kynurenic
      acid (Kyn, ionotropic glutamate receptor antagonist) into RVLM or the
      retrotrapezoid nucleus (RTN) eliminated or reduced PND, respectively, but did not
      change the effect of CO(2) on SND. Bilateral injection of Kyn or muscimol into
      the rostral ventral respiratory group (rVRG-pre-Botzinger region, also called
      CVLM) eliminated PND while increasing the stimulatory effect of CO(2) on SND.
      Muscimol injection into commissural part of the solitary tract nucleus (commNTS)
      had no effect on PND or SND activation by CO(2). As expected, injection of Kyn
      into RVLM or muscimol into commNTS virtually blocked the effect of carotid body
      stimulation on SND in rats with intact carotid sinus nerves. In conclusion, CO(2)
      increases SND by activating RVLM sympathoexcitatory neurons. The relevant central
      chemoreceptors are probably located within or close to RVLM and not in the NTS or
      in the rVRG-pre-Botzinger/CVLM region. RVLM sympathoexcitatory neurons may be
      intrinsically pH-sensitive and/or receive excitatory synaptic inputs from RTN
      chemoreceptors. Activation of the central respiratory network reduces the overall
      sympathetic response to CO(2), presumably by activating barosensitive CVLM
      neurons and inhibiting RTN chemoreceptors.

PMID- 16901946
TI  - Kinetics of ion channel modulation by cAMP in rat hippocampal neurones.
AB  - Ion channel regulation by cyclic AMP and protein kinase A is a major effector
      mechanism for monoamine transmitters and neuromodulators in the CNS.
      Surprisingly, there is little information about the speed and kinetic limits of
      cAMP-PKA-dependent excitability changes in the brain. To explore these questions,
      we used flash photolysis of caged-cAMP (DMNB-cAMP) to provide high temporal
      resolution. The resultant free cAMP concentration was calculated from separate
      experiments in which this technique was used, in excised patches, to activate
      cAMP-sensitive cyclic nucleotide-gated (CNG) channels expressed in Xenopus
      oocytes. In hippocampal pyramidal neurones we studied the modulation of a
      potassium current (slow AHP current, I(sAHP)) known to be targeted by multiple
      transmitter systems that use cAMP-PKA. Rapid cAMP elevation by flash photolyis of
      200 microm DMNB-cAMP completely inhibited the K(+) current. The estimated yield
      (1.3-3%) suggests that photolysis of 200 microm caged precursor is sufficient for
      full PKA activation. By contrast, extended gradual photolysis of 200 microm DMNB
      cAMP caused stable but only partial inhibition. The kinetics of rapid cAMP
      inhibition of the K(+) conductance (time constant 1.5-2 s) were mirrored by
      changes in firing patterns commencing within 500 ms of rapid cAMP elevation.
      Maximal increases in firing were short-lasting (< 60 s) and gave way to
      moderately enhanced levels of spiking. The results demonstrate how the fidelity
      of phasic monoamine signalling can be preserved by the cAMP-PKA pathway.

PMID- 16901947
TI  - Efferent-mediated control of basilar membrane motion.
AB  - Medial olivocochlear efferent (MOCE) neurones innervate the outer hair cells
      (OHCs) of the mammalian cochlea, and convey signals that are capable of
      controlling the sensitivity of the peripheral auditory system in a frequency
      specific manner. Recent methodological developments have allowed the effects of
      the MOCE system to be observed in vivo at the level of the basilar membrane (BM).
      These observations have confirmed earlier theories that at least some of the
      MOCE's effects are mediated via the cochlea's mechanics, with the OHCs acting as
      the mechanical effectors. However, the new observations have also provided some
      unexpected twists: apparently, the MOCEs can enhance the BM's responses to some
      sounds while inhibiting its responses to others, and they can alter the BM's
      response to a single sound using at least two separate mechanisms. Such
      observations put new constraints on the way in which the cochlea's mechanics, and
      the OHCs in particular, are thought to operate.

PMID- 16901949
TI  - Voxel-based morphometry of brain SPECT can detect the presence of active central
      nervous system involvement in systemic lupus erythematosus.
AB  - OBJECTIVE: To determine the value of voxel-based morphometry (VBM) of brain SPECT
      (single-photon emission computed tomography) images (BSI) in discriminating
      active central nervous system (CNS) manifestations in systemic lupus
      erythematosus (SLE) patients. PATIENTS AND METHODS: Forty SLE patients (mean age
      33 yrs) and 33 normal volunteers were submitted to BSI. SLE patients were
      screened for the presence of CNS involvement following the American College of
      Rheumatology (ACR) case definition. Patients with CNS infections, uraemia,
      diabetes and previous ischaemic or haemorrhagic stroke were excluded. Magnetic
      resonance imaging (MRI) scans were obtained in a 2T scanner (Elscint Prestige)
      with T1- and T2-weighted images. BSI were performed after injection of 1110 MBq
      (30 mCi) of (99m)Tc-ECD (ethyl-cysteinate-dimer). BSI were analysed using the
      statistical parametric mapping. After normalization, segmentation and smoothing
      the groups of SLE patients with active and inactive CNS manifestations and
      healthy volunteers were compared using VBM. Post-processed images were compared
      voxel-by-voxel using t-test in order to determine differences of intensity
      between groups. This analysis included grand mean scaling, proportional threshold
      masking (set to 0.4) and implicit masking. A P-value of 0.001 and cluster size of
      32 were taken into consideration. RESULTS: VBM analyses of BSI did not show any
      differences between SLE patients with inactive CNS involvement and normal
      controls. However, the group of SLE patients with active CNS involvement had a
      global hypoperfusion, more intense in the frontal, dorsolateral and medial
      temporal lobe when compared with SLE patients without CNS involvement (P = 0.001)
      and healthy volunteers (P = 0.001). CONCLUSION: VBM of BSI is a useful and
      objective method for detecting perfusion abnormalities in SLE patients, which is
      indicative of active CNS involvement. However, it is not helpful in
      differentiating the clinical sub-types of CNS involvement according to the ACR
      classification.

PMID- 16901948
TI  - Mechanisms underlying the temporal precision of sound coding at the inner hair
      cell ribbon synapse.
AB  - Our auditory system is capable of perceiving the azimuthal location of a low
      frequency sound source with a precision of a few degrees. This requires the
      auditory system to detect time differences in sound arrival between the two ears
      down to tens of microseconds. The detection of these interaural time differences
      relies on network computation by auditory brainstem neurons sharpening the
      temporal precision of the afferent signals. Nevertheless, the system requires the
      hair cell synapse to encode sound with the highest possible temporal acuity. In
      mammals, each auditory nerve fibre receives input from only one inner hair cell
      (IHC) synapse. Hence, this single synapse determines the temporal precision of
      the fibre. As if this was not enough of a challenge, the auditory system is also
      capable of maintaining such high temporal fidelity with acoustic signals that
      vary greatly in their intensity. Recent research has started to uncover the
      cellular basis of sound coding. Functional and structural descriptions of
      synaptic vesicle pools and estimates for the number of Ca(2+) channels at the
      ribbon synapse have been obtained, as have insights into how the receptor
      potential couples to the release of synaptic vesicles. Here, we review current
      concepts about the mechanisms that control the timing of transmitter release in
      inner hair cells of the cochlea.

PMID- 16901950
TI  - Cognitive predictors of social functioning improvements following cognitive
      remediation for schizophrenia.
AB  - A greater understanding of the links between cognitive and social functioning
      changes is needed to refine cognitive treatments for schizophrenia. To date,
      studies have been cross-sectional, and few have investigated the impact of
      cognitive change. This single-blind randomized controlled trial explored the
      links between changes in executive/memory functions and social behavior, as well
      as the moderating effect of cognitive remediation therapy (CRT). A total of 85
      participants with schizophrenia received 40 sessions of CRT (an individual
      psychological therapy aiming to improve attention, memory, and problem solving)
      or treatment-as-usual. At baseline, social functioning was significantly
      associated with "verbal working memory," "response inhibition," "verbal long-term
      memory," and "visuo-spatial long-term memory," but not "schema generation,"
      factors. However, only improvement in "schema generation" predicted improved
      social functioning. This was true whether or not participants had received CRT.
      These results suggest that cross-sectional associations between cognitive
      functions and social functioning may not offer the best means for identifying
      good targets for intervention. Improvement in the ability to generate new schemas
      has a beneficial impact on social functioning.

PMID- 16901951
TI  - Olfactory ability in the healthy population: reassessing presbyosmia.
AB  - Age-associated loss of olfactory function, or presbyosmia, has been described in
      many studies of olfactory ability. Presbyosmia has been ascribed to idiopathic
      causes despite recognition that many neurodegenerative diseases also induce loss
      of olfactory function and increase in incidence in the aged population. Often
      this olfactory loss is unnoticed or unreported by affected individuals. More
      effective olfactory function in women compared with men is another common feature
      of many studies of olfactory function. Here we report on normative data from an
      Australian population study (n = 942) that has been divided into 2 subpopulations
      and reassessed as (included) a population of healthy, nonmedicated, nonsmokers
      with no history of nasal problems (n = 485) and (excluded) a population of
      participants who were either medicated, smokers or had a history of nasal
      problems (n = 457). The "included" data set shows a strong relationship between
      self-reporting of olfactory sensitivity and olfactory function score. The
      included data set shows a small but significant decline in olfactory ability
      after 65 years of age and better olfactory function in females compared with
      males. Data from the excluded population show a marked decline in olfactory
      ability after 65 years of age, no difference between males and females, and a
      weak relationship between self-reporting of olfactory function and actual
      olfactory function. The power of this approach is that it provides a normative
      data set against which many factors such as medication schedules and pathological
      conditions can be compared.

PMID- 16901952
TI  - Sexual experience does not compensate for the disruptive effects of zinc sulfate-
      lesioning of the main olfactory epithelium on sexual behavior in male mice.
AB  - Recent studies point to an important role for the main olfactory epithelium (MOE)
      in regulating sexual behavior in male mice. We asked whether sexual experience
      could compensate for the disruptive effects of lesioning the MOE on sexual
      behavior in male mice. Male mice, which were either sexually naive or
      experienced, received an intranasal irrigation of either a zinc sulfate solution
      to destroy the MOE or saline. Sexual behavior in mating tests with an estrous
      female was completely abolished in zinc sulfate-treated male mice regardless of
      whether subjects were sexually experienced or not before the treatment.
      Furthermore, zinc sulfate treatment clearly disrupted olfactory investigation of
      both volatile and nonvolatile odors. Destruction of the MOE by zinc sulfate
      treatment was confirmed by a significant reduction in the expression of Fos
      protein in the main olfactory bulb following exposure to estrous female urine. By
      contrast, vomeronasal function did not seem to be affected by zinc sulfate
      treatment: nasal application of estrous female urine induced similar levels of
      Fos protein in the mitral and granule cells of the accessory olfactory bulb (AOB)
      of zinc sulfate- and saline-treated males. Likewise, the expression of soybean
      agglutinin, which stains the axons of vomeronasal organ neurons projecting to the
      glomerular layer of the AOB, was similar in zinc sulfate- and saline-treated male
      mice. These results show that the main olfactory system is essential for the
      expression of sexual behavior in male mice and that sexual experience does not
      overcome the disruptive effects of MOE lesioning on this behavior.

PMID- 16901953
TI  - Is glycine "sweet" to mice? Mouse strain differences in perception of glycine
      taste.
AB  - Glycine is an amino acid tasting sweet to humans. In 2-bottle tests, C57BL/6ByJ
      (B6) mice strongly prefer glycine solutions, whereas 129P3/J (129) mice do not,
      suggesting that they differ in perception of glycine taste. We examined this
      question using the conditioned taste aversion (CTA) generalization technique. CTA
      was achieved by injecting LiCl after drinking glycine, and next its
      generalization to 10 taste solutions (glycine, sucrose, saccharin, D-tryptophan,
      L-tryptophan, L-alanine, L-proline, L-glutamine, NaCl, and HCl) was examined by
      video recording licking behavior. Both B6 and 129 mice generalized the aversion
      to sucrose, saccharin, L-alanine, and L-proline and did not generalize it to
      NaCl, HCl, and L-tryptophan. This indicates that both B6 and 129 mice perceive
      the sweetness (i.e., a sucrose-like taste) of glycine. Thus, the lack of a
      glycine preference by 129 mice cannot be explained by their inability to perceive
      its sweetness. Strain differences were observed for CTA generalization to 2 amino
      acids: 129 mice generalized aversion to L-glutamine but not D-tryptophan, whereas
      B6 mice generalized it to D-tryptophan but not L-glutamine. 129.B6-Tas1r3
      congenic mice with 2 genotypes of the Tas1r3 locus (B6/129 heterozygotes and
      129/129 homozygotes) did not differ in aversion generalization, suggesting that
      the differences between 129 and B6 strains are not attributed to the Tas1r3
      allelic variants and that other, yet unknown, genes are involved in taste
      perception of amino acids.

PMID- 16901954
TI  - Deaf college students' mathematical skills relative to morphological knowledge,
      reading level, and language proficiency.
AB  - This study of deaf college students examined specific relationships between their
      mathematics performance and their assessed skills in reading, language, and
      English morphology. Simple regression analyses showed that deaf college students'
      language proficiency scores, reading grade level, and morphological knowledge
      regarding word segmentation and meaning were all significantly correlated with
      both the ACT Mathematics Subtest and National Technical Institute for the Deaf
      (NTID) Mathematics Placement Test scores. Multiple regression analyses identified
      the best combination from among these potential independent predictors of
      students' performance on both the ACT and NTID mathematics tests. Additionally,
      the participating deaf students' grades in their college mathematics courses were
      significantly and positively associated with their reading grade level and their
      knowledge of morphological components of words.

PMID- 16901955
TI  - Rheumatoid factor and antibodies to cyclic citrullinated peptides are associated
      with severe extra-articular manifestations in rheumatoid arthritis.
AB  - OBJECTIVE: To study antibodies to cyclic citrullinated peptides (anti-CCP) and
      rheumatoid factor in patients with active, severe extra-articular rheumatoid
      arthritis (ExRA) compared with controls without ExRA. METHODS: 35 consecutive
      patients with severe ExRA manifestations according to predefined criteria were
      studied. 70 patients with rheumatoid arthritis, but no ExRA manifestations,
      individually matched for age, sex and disease duration, served as controls.
      Patients were included when ExRA was diagnosed, before any new treatment was
      started. Anti-CCPs were detected with ELISA, rheumatoid factor was quantified
      using nephelometry and anti-nuclear antibodies (ANA) were investigated using
      indirect immune fluorescence. RESULTS: Anti-CCPs were detected in 77% of patients
      with ExRA versus 56% of controls without ExRA (p = 0.03). Anti-CCP levels also
      tended to be higher in patients with ExRA (p = 0.09). Rheumatoid factor was
      detected in 94% v 71% of patients and controls, respectively (p = 0.006), and
      rheumatoid factor levels were higher in patients with ExRA (median interquartile
      range (IQR) 245 IU/ml (94-604) v 73 IU/ml (not detected-165); p = 0.001). Levels
      and occurrence of ANA did not differ between patients with ExRA and controls.
      Patients with ExRA had higher swollen joint counts and C reactive protein levels,
      but no correlations were found between anti-CCP or rheumatoid factor levels and
      these measures within the ExRA group. CONCLUSION: Rheumatoid factor is strongly
      associated with severe ExRA manifestations in patients with rheumatoid arthritis,
      and a similar but weaker association exists for anti-CCPs. This suggests a role
      for rheumatoid factor and anti-CCP in the pathogenesis of ExRA.

PMID- 16901956
TI  - High prevalence of the metabolic syndrome in patients with systemic lupus
      erythematosus: association with disease characteristics and cardiovascular risk
      factors.
AB  - BACKGROUND: The metabolic syndrome is an independent risk factor for ischaemic
      heart disease. Patients with systemic lupus erythematosus (SLE) have accelerated
      atherosclerosis; however, there are no controlled studies of the metabolic
      syndrome in patients with SLE. OBJECTIVE: To compare the prevalence of the
      metabolic syndrome in patients with SLE and controls and to evaluate its
      relationship to other cardiovascular risk factors and inflammation. METHODS: 102
      patients with SLE and 101 controls were studied. The prevalence of the metabolic
      syndrome was compared in patients and controls using the National Cholesterol
      Education Program Adult Treatment Panel III (NCEP) and the World Health
      Organization (WHO) definitions, and associations with cardiovascular risk factors
      and lupus characteristics were examined. RESULTS: The metabolic syndrome was
      present in 32.4% of patients and in 10.9% of controls subjects (p<0.001) using
      the WHO definition that requires direct determination of insulin resistance, and
      in 29.4% of patients with SLE and in 19.8% of controls (p = 0.14) using the NCEP
      definition. Among patients with SLE, both definitions were significantly
      associated with higher concentrations of C reactive protein (p = 0.001) and the
      NCEP definition was significantly associated with higher concentrations of
      homocysteine (p<0.001), lipoprotein (a) (p = 0.02) and cholesterol (p = 0.04).
      Neither lupus disease activity nor damage scores were associated with the
      metabolic syndrome. CONCLUSIONS: Patients with SLE have a higher prevalence of
      insulin resistance and consequently of the WHO-defined metabolic syndrome than
      controls. In patients with SLE, the metabolic syndrome was associated with higher
      levels of inflammation and may provide a link between inflammation and increased
      cardiovascular risk.

PMID- 16901958
TI  - Development and validation of a consensus methodology for the classification of
      the ANCA-associated vasculitides and polyarteritis nodosa for epidemiological
      studies.
AB  - BACKGROUND: The classification of antineutrophil cytoplasmic antibody-associated
      vasculitis (AAV) and polyarteritis nodosa (PAN) for epidemiology studies is
      confusing. The existing schemes such as American College of Rheumatology (ACR)
      criteria, Chapel Hill Consensus Conference (CHCC) definitions and Lanham criteria
      produce overlapping and conflicting classifications, making it difficult to
      compare incidence figures. AIM: To develop a consensus method of using these
      criteria and definitions for epidemiological studies to permit comparison without
      confounding by classification. METHODS: A stepwise algorithm was developed by
      consensus between a group of doctors interested in the epidemiology of
      vasculitis. The aim was to categorise patients with Wegener's granulomatosis,
      microscopic polyangiitis (MPA), Churg-Strauss syndrome (CSS) and PAN into single
      clinically relevant categories. The ACR and Lanham criteria for CSS, and ACR
      criteria for Wegener's granulomatosis were applied first, as these were
      considered to be the most specific. Surrogate markers for Wegener's
      granulomatosis were included to distinguish Wegener's granulomatosis from MPA.
      MPA was classified using the CHCC definition and surrogate markers for renal
      vasculitis. Finally, PAN was classified using the CHCC definition. The algorithm
      was validated by application to 20 cases from each centre and 99 from a single
      centre, followed by a paper case exercise. RESULTS: A four-step algorithm was
      devised. It successfully categorises patients into a single classification. There
      was good correlation between observers in the paper case exercise (91.5%;
      unweighted kappa = 0.886). CONCLUSION: The algorithm achieves its aim of reliably
      classifying patients into a single category. The use of the algorithm in
      epidemiology studies should permit comparison between geographical areas.

PMID- 16901957
TI  - Proteomic analysis of secreted proteins in early rheumatoid arthritis: anti
      citrulline autoreactivity is associated with up regulation of proinflammatory
      cytokines.
AB  - OBJECTIVES: To identify peripheral blood autoantibody and cytokine profiles that
      characterise clinically relevant subgroups of patients with early rheumatoid
      arthritis using arthritis antigen microarrays and a multiplex cytokine assay.
      METHODS: Serum samples from 56 patients with a diagnosis of rheumatoid arthritis
      of <6 months' duration were tested. Cytokine profiles were also determined in
      samples from patients with psoriatic arthritis (PsA) and ankylosing spondylitis
      (n = 21), and from healthy individuals (n = 19). Data were analysed using Kruskal
      Wallis test with Dunn's adjustment for multiple comparisons, linear correlation
      tests, significance analysis of microarrays (SAM) and hierarchical clustering
      software. RESULTS: Distinct antibody profiles were associated with subgroups of
      patients who exhibited high serum levels of tumour necrosis factor (TNF)alpha,
      interleukin (IL)1beta, IL6, IL13, IL15 and granulocyte macrophage colony
      stimulating factor. Significantly increased autoantibody reactivity against
      citrullinated epitopes was observed in patients within the cytokine "high"
      subgroup. Increased levels of TNFalpha, IL1alpha, IL12p40 and IL13, and the
      chemokines eotaxin/CCL11, monocyte chemoattractant protein-1 and interferon
      inducible protein 10, were present in early rheumatoid arthritis as compared with
      controls (p<0.001). Chemokines showed some of the most impressive differences.
      Only IL8/CXCL8 concentrations were higher in patients with PsA/ankylosing
      spondylitis (p = 0.02). CONCLUSIONS: Increased blood levels of proinflammatory
      cytokines are associated with autoantibody targeting of citrullinated antigens
      and surrogate markers of disease activity in patients with early rheumatoid
      arthritis. Proteomic analysis of serum autoantibodies, cytokines and chemokines
      enables stratification of patients with early rheumatoid arthritis into molecular
      subgroups.

PMID- 16901959
TI  - No efficacy of subcutaneous methotrexate in active ankylosing spondylitis: a 16
      week open-label trial.
AB  - OBJECTIVE: To examine the potential therapeutic effect of methotrexate 20 mg
      given weekly as subcutaneous injections to 20 patients with ankylosing
      spondylitis refractory to non-steroidal antirheumatic drugs. PATIENTS AND
      METHODS: 20 patients with ankylosing spondylitis, a mean Bath Ankylosing
      Spondylitis Disease Activity Index (BASDAI) score of 5.6 (range 4-9.3) and
      predominantly axial manifestations were treated with weekly 15 mg methotrexate
      subcutaneously for 4 weeks, which was then increased to 20 mg subcutaneously for
      the next 12 weeks. Clinical outcome assessments included, among others, BASDAI
      score physical function, spinal mobility, patients' and physicians' global
      assessment (visual analogue scale), peripheral joint assessment, quality of life
      (Short Form 36) and C reactive protein. The primary end point of the study was a
      20% improvement on the ASsessments in Ankylosing Spondylitis (ASAS 20) scale.
      RESULTS: Using an intention-to-treat analysis, ASAS 20 was achieved in only 25%
      of patients. An ASAS 40 response was achieved in 10% of patients, and no patient
      reached an ASAS 70 response or the ASAS criteria for partial remission. For the
      mean BASDAI score, no change was observed between baseline and week 16 (baseline
      5.6 v week 16, 5.6). No improvement was observed in any of the clinical
      parameters or C reactive protein, except a small but non-significant decrease in
      the number of swollen joints. CONCLUSIONS: In this open study, methotrexate did
      not show any benefit for axial manifestations in patients with active ankylosing
      spondylitis beyond the expected placebo response.

PMID- 16901961
TI  - Toxicity of used orthodontic archwires assessed by three-dimensional cell
      culture.
AB  - The aim of the present study was to determine whether used orthodontic wires made
      of different materials cause toxicity and loss of viability on three-dimensional
      (3D) cell cultures. Three types of orthodontic wires, stainless steel, Nitinol,
      and TMA (n = 9) which had been used clinically in fixed appliances for a period
      of 1 month, were retrieved at random from five patients. Both upper and lower
      archwires were collected and subjected to two different protocols: to assess
      toxicity, two pieces of each wire were placed on 3D cell cultures (reconstituted
      human epithelium); to investigate the possibility of cell damage, the 3-(4,5
      dimethylthiazol-2-yl)2,5-diphenyl tetrazolium bromide (MTT) assay was used and
      haematoxylin and eosin staining was performed to evaluate morphological changes.
      Copper wire served as the control to determine the morphology of severe toxicity,
      and native cell cultures and silk were used as the negative controls.
      Morphological evaluation of the native cell cultures revealed no toxic reactions.
      The ranking, from mild to severe toxicity was as follows: stainless steel <
      Nitinol = TMA. There were no significant differences between TMA and Nitinol. The
      MTT assay revealed the following mean percentage values for viability: native
      cell line (negative control), 100; stainless steel, 102.25; TMA, 87.4; Nitinol,
      85.3; and copper wire (positive control) 57.2. Histological evaluation of the 3D
      cell cultures showed no severe toxicity or loss of viability for any of the
      wires. However, relative comparison between the different wires revealed that
      stainless steel induced less toxicity/loss of viability compared with TMA and
      Nitinol wire.

PMID- 16901960
TI  - Efficacy of tumour necrosis factor blockers in reducing uveitis flares in
      patients with spondylarthropathy: a retrospective study.
AB  - OBJECTIVE: To evaluate the efficacy of anti-tumour necrosis factor (TNF)
      treatments (given for rheumatological manifestations) in reducing uveitis flares
      in patients with spondylarthropathy in daily practice. METHODS: A retrospective
      observational study of all patients with spondylarthropathy with at least one
      uveitis flare treated with anti-TNF in one centre (December 1997-December 2004).
      The number of uveitis flares per 100 patient-years was compared before and during
      anti-TNF treatment; each patient was his or her own control. The relative risk
      (RR) and the number needed to treat (NNT) were calculated. RESULTS: 46 patients
      with spondylarthropathy treated with anti-TNF drugs had at least one uveitis
      flare (33 treated with anti-TNF antibodies, infliximab or adalimumab, and 13 with
      soluble TNF receptor, etanercept). The mean age at first symptoms was 26 years,
      71% were men. Patients were followed for 15.2 years (mean) before anti-TNF versus
      1.2 years during anti-TNF treatment. The number of uveitis flares per 100 patient
      years before and during anti-TNF were, respectively: for all anti-TNF treatments,
      51.8 v 21.4 (p = 0.03), RR = 2.4, NNT = 3 (95% confidence interval (CI) 2 to 5);
      for soluble TNF receptor-54.6 v 58.5 (p = 0.92), RR = 0.9; and for anti-TNF
      antibodies-50.6 v 6.8 (p = 0.001), RR = 7.4, NNT = 2 (95% CI 2 to 5). CONCLUSION:
      Anti-TNF treatments were efficacious in decreasing the number of uveitis flares
      in patients with spondylarthropathy. Anti-TNF antibodies decreased the rate of
      uveitis flares, whereas soluble TNF receptor did not seem to decrease this rate.
      These results could have consequences for the choice of anti-TNF treatment in
      certain patients.

PMID- 16901962
TI  - Reproducibility of soft tissue landmarks on three-dimensional facial scans.
AB  - This study evaluated the reproducibility of 24 soft tissue landmarks on six three
      dimensional (3D) facial scans. The scans were taken on a DSP400 facial scanner
      and were viewed using a customized software program. Intraoperator data were
      obtained by one researcher placing the 24 landmarks on all six scans a total of
      30 times. Thirty different orthodontists of varying experience were then asked to
      place all 24 landmarks on each of the six facial scans in order to establish
      interoperator reproducibility. The standard deviations (SDs) from the mean were
      calculated from the data for each individual landmark in the x-, y-, and z-axes.
      For the intraoperator data, 12 of the 24 landmarks were found to be reproducible
      to within a 1 mm SD for each plane of space. The interoperator data showed lower
      reproducibility with just two landmarks showing less than a 1 mm SD in all three
      planes of space. Familiarity with 3D facial scans and associated software
      programs is important in improving reproducibility. In addition, the landmarks
      investigated in this study included those not often used. It is suggested that
      landmarks showing poor reproducibility for both inter- and intraoperator data
      should be avoided, if at all possible, or at least used with caution.

PMID- 16901963
TI  - Adiponectin deficiency does not affect the inflammatory response to endotoxin or
      concanavalin a in mice.
AB  - Adiponectin (APN) is an adipocyte-derived protein that regulates insulin
      sensitivity and displays antiinflammatory activities in a variety of experimental
      models. The present study aimed at investigating the effect of APN deficiency on
      the inflammatory response to endotoxin (lipopolysaccharide, LPS) and Concanavalin
      A (ConA) in vivo in mice. Administration of a high dose of LPS (100 microg/mouse)
      induced production of comparable amounts of IL-6, TNFalpha, and interferon-gamma
      in wild-type (WT) and APN knockout (KO) mice. Furthermore, LPS-induced
      hypoglycemia, anorexia, and body weight loss did not differ between WT and APN KO
      mice. Administration of a low dose of LPS (100 or 10 ng/g) in association with d
      galactosamine induced equivalent mortality rates, hepatotoxicity, and serum IL-6
      in WT and APN KO mice. Finally, ConA-induced cytokine production and
      hepatotoxicity were not significantly different between WT and APN KO mice. These
      data indicate that--despite its well-described role as an antiinflammatory
      molecule--endogenous APN does not play a critical role in modulating the
      inflammatory responses to LPS and ConA in mice.

PMID- 16901964
TI  - Mineralocorticoid receptor antagonist reduces renal injury in rodent models of
      types 1 and 2 diabetes mellitus.
AB  - To determine whether mineralocorticoid receptor (MR) activation plays a role in
      diabetic renal injury and whether this role differs in types 1 and 2 diabetes
      mellitus, we examined the effect of a MR antagonist on renal injury in rodent
      models of type 1 (streptozotocin-treated rat) and type 2 (db/db mouse) diabetes.
      We studied three groups of 8-wk-old, uninephrectomized Wistar rats for 4 wk:
      diabetic streptozotocin- (55 mg/kg) treated rats (n = 11), diabetic
      streptozotocin-treated rats receiving the MR antagonist eplerenone (n = 15), and
      nondiabetic rats (n = 9). In addition, we studied three groups of 8-wk-old mice
      for 16 wk: diabetic db/db mice (n = 10), diabetic db/db mice treated with
      eplerenone (n = 8), and nondiabetic, db/+ littermates (n = 11). Diabetic rats and
      mice developed albuminuria and histopathological evidence of renal injury,
      including glomerular hypertrophy, mesangial expansion, and tubulointerstitial
      injury as well as increased renal cortical levels of MR protein, MR mRNA, TGFbeta
      mRNA, and osteopontin mRNA. All of these changes were significantly reduced by
      treatment with eplerenone except for the elevated MR levels. The beneficial
      effects of eplerenone were not attributable to changes in blood pressure or
      glycemia. In summary, MR expression was increased in kidneys of diabetic rodents,
      and MR antagonists effectively reduced diabetic renal injury irrespective of the
      species or specific cause of the diabetes. Thus, these data suggest that MR
      activation is a critical factor in the early pathogenesis of renal disease in
      both type 1 and type 2 diabetes mellitus.

PMID- 16901965
TI  - Estrogen regulates epithelial cell deformability by modulation of cortical
      actomyosin through phosphorylation of nonmuscle myosin heavy-chain II-B
      filaments.
AB  - The objective of the study was to understand how estrogen modulates the rigidity
      of the cytoskeleton in epithelial cells. Estrogen depletion decreased, and
      treatment with 17beta-estradiol increased deformability of cervical-vaginal
      epithelial cells. Estrogen also induced redistribution of nonmuscle myosin II-B
      (NMM-II-B); lesser interaction of NMM-II-B with actin; increased phosphorylation
      of NMM-II-B-heavy chains at threonine and serine residues; and decreased
      filamentation of NMM-II-B in vitro. The effects of 17beta-estradiol were time and
      dose related and could be mimicked by diethylstilbestrol. The effects of estrogen
      were blocked by cotreatment with antisense oligonucleotide for the estrogen
      receptor-alpha and inhibited by ICI-182,780 and tamoxifen; omission of epithelial
      growth factor (EGF) from the culture medium; and cotreatments with the EGF
      receptor inhibitor AG1478, the ERK-MAPK inhibitor PD98059, the casein kinase-II
      (CK2) inhibitor 5,6-dichloro-1-beta-(D)-ribofuranosylbenzimidazole, the Rho
      associated kinase inhibitor Y-27632, and the nonspecific phosphatase inhibitor
      okadaic acid. Coadministration of 5,6-dichloro-1-beta-(D)
      ribofuranosylbenzimidazole plus okadaic acid blocked the 17beta-estradiol effect.
      H-89 or LY294002 did not significantly affect estrogen effects. Treatment with
      estrogen increased activation of ERK1/2 and CK2 activity. These data suggest a
      novel pathway of estrogen regulation of the cytoskeleton in epithelial cells. The
      effect is mediated by estrogen receptor-alpha and involves in part the EGF-EGF
      receptor and ERK-MAPK cascades as proximal signaling networks and the CK2 and Rho
      associated kinase-regulated myosin heavy chain phosphatase as terminal effectors.
      Augmented phosphorylation of NMM-II-B can block filamentation and induce
      disassociation of the myosin from the cortical actin, and disruption of the
      actomyosin ring can increase cell deformability. This mechanism can explain
      estrogen regulation of paracellular permeability in cervical-vaginal epithelia in
      vivo.

PMID- 16901966
TI  - Low-dose dopamine agonist administration blocks vascular endothelial growth
      factor (VEGF)-mediated vascular hyperpermeability without altering VEGF receptor
      2-dependent luteal angiogenesis in a rat ovarian hyperstimulation model.
AB  - No specific treatment is available for ovarian hyperstimulation syndrome (OHSS),
      the most important complication in infertile women treated with gonadotropins.
      OHSS is caused by increased vascular permeability (VP) through ovarian
      hypersecretion of vascular endothelial growth factor (VEGF)-activating VEGF
      receptor 2 (VEGFR-2). We previously demonstrated in an OHSS rodent model that
      increased VP was prevented by inactivating VEGFR-2 with a receptor antagonist
      (SU5416). However, due to its toxicity (thromboembolism) and disruption of VEGFR
      2-dependent angiogenic processes critical for pregnancy, this kind of compound
      cannot be used clinically to prevent OHSS. Dopamine receptor 2 (Dp-r2) agonists,
      used in the treatment of human hyperprolactinemia including pregnancy, inhibit
      VEGFR-2-dependent VP and angiogenesis when administered at high doses in animal
      cancer models. To test whether VEGFR-2-dependent VP and angiogenesis could be
      segregated in a dose-dependent fashion with the Dp-r2 agonist cabergoline, a well
      established OHSS rat model supplemented with prolactin was used. A 100 microg/kg
      low-dose Dp-r2 agonist cabergoline reversed VEGFR-2-dependent VP without
      affecting luteal angiogenesis through partial inhibition of ovarian VEGFR-2
      phosphorylation levels. No luteolytic effects (serum progesterone levels and
      luteal apoptosis unaffected) were observed. Cabergoline administration also did
      not affect VEGF/VEGFR-2 ovarian mRNA levels. Results in the animal model and the
      safe clinical profile of Dp-r2 agonists encouraged us to administer cabergoline
      to oocyte donors at high risk for developing the syndrome. Prophylactic
      administration of cabergoline (5-10 microg/kg x d) decreased the occurrence of
      OHSS from 65% (controls) to 25% (treatment). Therefore, a specific, safe
      treatment for OHSS is now available.

PMID- 16901967
TI  - The orphan nuclear receptor, NOR-1, is a target of beta-adrenergic signaling in
      skeletal muscle.
AB  - beta-Adrenergic receptor (beta-AR) agonists induce Nur77 mRNA expression in the
      C2C12 skeletal muscle cell culture model and elicit skeletal muscle hypertrophy.
      We previously demonstrated that Nur77 (NR4A1) is involved in lipolysis and gene
      expression associated with the regulation of lipid homeostasis. Subsequently it
      was demonstrated by another group that beta-AR agonists and cold exposure-induced
      Nur77 expression in brown adipocytes and brown adipose tissue, respectively.
      Moreover, NOR-1 (NR4A3) was hyperinduced by cold exposure in the nur77(-/-)
      animal model. These studies underscored the importance of understanding the role
      of NOR-1 in skeletal muscle. In this context we observed 30-480 min of beta-AR
      agonist treatment significantly and transiently increased expression of the
      orphan nuclear receptor NOR-1 in both mouse skeletal muscle tissue (plantaris)
      and C2C12 skeletal muscle cells. Specific beta(2)- and beta(3)-AR agonists had
      similar effects as the pan-agonist and were blocked by the beta-AR antagonist
      propranolol. Moreover, in agreement with these observations, isoprenaline also
      significantly increased the activity of the NOR-1 promoter. Stable exogenous
      expression of a NOR-1 small interfering RNA (but not the negative control small
      interfering RNA) in skeletal muscle cells significantly repressed endogenous NOR
      1 mRNA expression and led to changes in the expression of genes involved in the
      control of lipid use and muscle mass underscored by a dramatic increase in
      myostatin mRNA expression. Concordantly the myostatin promoter was repressed by
      NOR-1 expression. In conclusion, NOR-1 is highly responsive to beta-adrenergic
      signaling and regulates the expression of genes controlling fatty acid use and
      muscle mass.

PMID- 16901968
TI  - Epithelial-specific and stage-specific functions of insulin-like growth factor-I
      during postnatal mammary development.
AB  - Postnatal development of the mammary gland requires interactions between the
      epithelial and stromal compartments, which regulate actions of hormones and
      growth factors. IGF-I is expressed in both epithelial and stromal compartments
      during postnatal development of the mammary gland. However, little is known about
      how local expression of IGF-I in epithelium or stroma regulates mammary growth
      and differentiation during puberty and pregnancy-induced alveolar development.
      The goal of this study was to investigate the mechanisms of IGF-I actions in the
      postnatal mammary gland and test the hypothesis that IGF-I expressed in stromal
      and epithelial compartments has distinct functions. We established mouse lines
      with inactivation of the igf1 gene in mammary epithelium by crossing igf1/loxP
      mice with mouse lines expressing Cre recombinase under the control of either the
      mouse mammary tumor virus long-terminal repeat or the whey acidic protein gene
      promoter. Epithelial-specific loss of IGF-I during pubertal growth resulted in
      deficits in ductal branching. In contrast, heterozygous reduction of IGF-I
      throughout the gland decreased expression of cyclins A2 and B1 during pubertal
      growth and resulted in alterations in proliferation of the alveolar epithelium
      and milk protein levels during pregnancy-induced differentiation. Reduction in
      epithelial IGF-I at either of these stages had no effect on these indices. Taken
      together, our results support distinct roles for IGF-I expressed in epithelial
      and stromal compartments in mediating growth of the postnatal mammary gland.

PMID- 16901970
TI  - Structural differences in the hinge region of the glycoprotein hormone receptors:
      evidence from the sulfated tyrosine residues.
AB  - Tyrosine sulfation is a late posttranslational modification of proteins that
      takes place in the Golgi network. In the past few years, this process has been
      identified as an important modulator of protein-protein interactions. Sulfated
      tyrosine residues have recently been identified in the C-terminal, so-called
      hinge region of the ectodomain of glycoprotein hormone receptors [TSH,
      LH/chorionic gonadotropin (CG), and FSH receptors] and were shown to play an
      important role in the interaction with their natural ligands. The position of two
      sulfated tyrosine residues in a Y-D/E-Y motif appears perfectly conserved in the
      alignment of TSH and LH receptors from different species, and site-directed
      mutagenesis experiments demonstrated that sulfation of the first residue of this
      motif was responsible for the functional effect on hormone binding. In contrast,
      the corresponding motif is not conserved in the FSH receptor, in which the first
      tyrosine residue is missing: the Y-D/E-Y motif is replaced by F(333)DY(335). We
      extend here our previous observation that, in this case, it is sulfation of the
      second sole tyrosine residue in the motif that is functionally important. An
      LH/CG receptor harboring an F(331)DY(333) motif (i.e. displaying decreased
      sensitivity to human CG) was used as a backbone in which short portions of the
      FSH receptor were substituted. Segments from the FSH receptor capable of
      restoring sensitivity to human CG were identified by transfection of the chimeras
      in COS-7 cells. These experiments identified key amino acid residues in the hinge
      region of the FSH receptor associated with the functional role of the second
      sulfated tyrosine residue in a Y-D/E-Y motif, allowing for efficient hormone
      binding. The experiments represent strong evidence that structural differences in
      the hinge regions of FSH and LH/CG receptors play a significant role in hormone
      receptor-specific recognition.

PMID- 16901969
TI  - Role of chromatin accessibility in the occupancy and transcription of the insulin
      gene by the pancreatic and duodenal homeobox factor 1.
AB  - The pancreatic and duodenal homeobox factor 1 (Pdx-1) is a Hox-like transcription
      factor that is responsible for the activation of the insulin gene. Previous
      studies have demonstrated the interaction in vitro of Pdx-1 with short (20-40
      nucleotide) DNA fragments corresponding to A boxes of the insulin promoter.
      Precisely how Pdx-1 binds to DNA in the complex milieu of chromatin, however, has
      never been studied. In this study, we explored how Pdx-1-DNA interactions might
      be influenced by chromatin accessibility at the insulin gene in beta-cells
      (betaTC3) vs. pancreatic ductal cells (mPAC). We demonstrate that Pdx-1 occupies
      the endogenous insulin promoter in betaTC3 cells but not in mPAC cells, a finding
      that is independent of the intracellular Pdx-1 protein concentration. Based on
      micrococcal nuclease protection assays, the difference in promoter binding
      between the two cell types appears to be secondary to chromatin accessibility at
      predicted Pdx-1 binding sites between bp -126 to -296 (relative to the
      transcriptional start site) of the insulin promoter. Binding studies using
      purified Pdx-1 and reconstituted chromatin in vitro suggest that the positioning
      of a nucleosome(s) within this crucial region of the promoter might account for
      differences in chromatin accessibility. Consistent with these observations,
      fluorescence colocalization studies show that Pdx-1 does not occupy regions of
      compacted, nucleosome-rich chromatin within the nucleus. Our findings suggest a
      model whereby insulin transcription in the beta-cell is at least partially
      facilitated by enhanced chromatin accessibility within a crucial regulatory
      region between bp -126 to -296, thereby permitting occupancy by transactivators
      such as Pdx-1.

PMID- 16901971
TI  - Indole-3-carbinol selectively uncouples expression and activity of estrogen
      receptor subtypes in human breast cancer cells.
AB  - Estrogen-responsive breast cancer cells, such as MCF7 and T47D cells, express
      both estrogen receptor (ER)-alpha (ERalpha) and ERbeta. Indole-3-carbinol (I3C)
      strongly down-regulated ERalpha protein and transcript levels, without altering
      the level of ERbeta protein, in both cell lines. In cells transfected with the
      ERalpha promoter linked to a luciferase gene reporter, I3C ablated ERalpha
      promoter activity. Propyl pyrazole triol (PPT) is a highly selective ERalpha
      agonist, whereas, 17beta-estradiol activates both ERalpha and ERbeta. I3C
      treatment inhibited the PPT- and 17beta-estradiol-induced proliferation of breast
      cancer cells, disrupted the PPT and 17beta-estradiol stimulation of estrogen
      response element (ERE)-driven reporter plasmid activity as well as of endogenous
      progesterone receptor transcripts. Using an in vitro ERE binding assay, I3C was
      shown to inhibit the level of functional ERalpha and stimulated the level of ERE
      binding ERbeta even though the protein levels of this receptor remained constant.
      In ERalpha-/ERbeta+ MDA-MB-231 breast cancer cells, I3C treatment stimulated a 6
      fold increase in binding of ERbeta to the ERE. I3C also induced ERE- and
      activator protein 1-driven reporter plasmid activities in the absence of an ER
      agonist, suggesting that ERbeta is activated in indole-treated cells. Taken
      together, our results demonstrate that the expression and function of ERalpha and
      ERbeta can be uncoupled by I3C with a key cellular consequence being a
      significantly higher ERbeta:ERalpha ratio that is generally highly associated
      with antiproliferative status of human breast cancer cells.

PMID- 16901972
TI  - Characterization of vitamin D receptor ligands with cell-specific and dissociated
      activity.
AB  - Although the main role of 1alpha,25-dihydroxyvitamin D(3) [1,25-(OH)(2)D(3)] is
      to regulate calcium homeostasis, the valuable therapeutic applications of this
      compound have led to the search of new 1,25-(OH)(2)D(3)-vitamin D receptor (VDR)
      ligands with less side effects. In this work we have characterized seven 1,25
      (OH)(2)D(3) derivatives (ZK136607, ZK161422, ZK157202, ZK159222, ZK168492,
      ZK191732, and ZK168289). ZK157202 is an agonist that gives a pattern similar to
      that of 1,25-(OH)(2)D(3) or ZK161422 in limited trypsin digestion assays, is able
      to recruit p160 and VDR-interacting protein 205 coactivators, is as potent as
      1,25-(OH)(2)D(3) to stimulate vitamin D response element-dependent transcription
      in HeLa cells, and acts as a superagonist in human embryonic kidney 293T cells.
      This compound is also more potent than the natural ligand to transrepress the
      activation of the retinoic acid receptor beta2 promoter by retinoic acid and the
      response of the collagenase promoter to 4alpha-12-O-tetradecanoylphorbol 13
      acetate. ZK136607, ZK168492, ZK191732, and ZK168289 have a profile similar to
      that of the partial antagonist ZK159222. They induce an antagonistic-type
      proteolytic pattern, do not recruit classical coactivators, and have little
      transactivation potency. However, they act in a cell context-dependent manner
      because they lack activity in HeLa cells while presenting some agonistic activity
      in human embryonic kidney 293T cells, or vice versa. Furthermore, some of these
      compounds have a dissociated activity: they cannot transactivate but they are as
      potent as 1,25-(OH)(2)D(3) in transrepression assays. Together our results
      demonstrate the existence of novel VDR ligands with variable biological functions
      and dissociated activity. They should represent useful tools for studying VDR
      function and could have therapeutic utility.

PMID- 16901973
TI  - Involvement of the pituitary-specific transcription factor pit-1 in
      somatolactotrope cell growth and death: an approach using dominant-negative pit-1
      mutants.
AB  - The anterior pituitary-specific transcription factor Pit-1 was initially
      identified and cloned as a transactivator of the prolactin (PRL) and GH genes and
      later as a regulator of the TSHb gene. It was found to be a major developmental
      regulator, because natural Pit-1 gene mutations cause a dwarf phenotype in mice
      and cause combined pituitary hormone deficiency associated with pituitary
      hypoplasia in humans. To further investigate the growth-promoting effects of Pit
      1, we used a strategy based on the use of dominant-negative Pit-1 mutants as an
      alternative means of inactivating endogenous Pit-1 functions. R271W, a Pit-1
      mutant identified in one allele in patients with severe combined pituitary
      hormone deficiency, and Pit-1Delta1-123, a deletion mutant in which only the DNA
      binding domain of Pit-1 is conserved, were generated, and their ability to
      abolish the effects of the endogenous native Pit-1 in the differentiated
      proliferating somatolactotrope GH4C1 cell line was investigated. Enforced
      expression of the dominant-negative mutants in GH4C1 cells using recombinant
      lentiviral vectors decreased the levels of expression of known Pit-1 target genes
      such as PRL and GH, abolished the hormone release, and reduced cell viability by
      decreasing the growth rate and inducing apoptosis via a caspase-independent
      pathway. These results show for the first time that the growth-promoting effects
      of Pit-1 are at least partly due to the fact that this transcription factor
      prevents apoptotic cell death.

PMID- 16901974
TI  - Phenotypic heterogeneity in hereditary non-polyposis colorectal cancer: identical
      germline mutations associated with variable tumour morphology and
      immunohistochemical expression.
AB  - BACKGROUND: Hereditary non-polyposis colorectal cancer (HNPCC) is associated with
      high risks for colorectal and endometrial cancer, young age at onset and an
      increased risk of multiple primary tumours. Colorectal cancer in HNPCC is
      characterised by poor tumour differentiation, an expanding growth pattern, and a
      pronounced lymphocytic reaction with tumour-infiltrating lymphocytes. AIMS AND
      METHODS: The mutation spectrum in HNPCC is diverse and in order to clarify
      whether the HNPCC tumour phenotype is influenced by the underlying genetic
      alteration, 29 colorectal cancers and 12 adenomas from 24 individuals in two
      HNPCC families were morphologically and immunohistochemically characterised.
      RESULTS: The tumour morphology as well as the immunohistochemical expression of
      beta-catenin varied extensively within the families as well as between
      synchronous/metachronous colorectal cancers from the same individual. Poor tumour
      differentiation, an expanding growth pattern, and tumour-infiltrating lymphocytes
      occurred at higher frequencies in proximal tumours, whereas distal colorectal
      cancers often lacked distinct HNPCC-associated morphological features.
      CONCLUSIONS: The clinical, morphological and immunohistochemical variability
      observed within these families indicates that other mechanisms than the
      underlying germline mutation influence the HNPCC phenotype. Since morphological
      features linked to HNPCC are less frequent in distal cancers, it may be
      particularly relevant to obtain family history and age of onset in these tumours
      in order to identify individuals with HNPCC.

PMID- 16901976
TI  - Advance directives, future selves and decision-making.

PMID- 16901975
TI  - Altered p-STAT3 (tyr705) expression is associated with histological grading and
      intratumour microvessel density in hepatocellular carcinoma.
AB  - BACKGROUND: Constitutive activation of signal transducer and activator of
      transcription 3 at tyrosine residue 705 (p-STAT3 (tyr705)) has been associated
      with many types of human cancers. However, its potential roles and biological
      effects in hepatocellular carcinoma (HCC) are not well established. AIM: To
      explore whether an altered p-STAT3 (tyr705) expression is associated with
      angiogenesis or proliferation and thereby plays a part in HCC development.
      METHODS: Paraffin-wax-embedded sections from 69 patients with HCC were collected
      in this study. Using a semiquantitative immunohistochemical staining method, the
      expression patterns of p-STAT3 (tyr705) in both HCC lesions and the adjacent non
      tumorous liver parenchyma were analysed. The results obtained were further
      correlated with intratumour microvessel density (MVD), Ki-67 expression,
      clinicopathological parameters and overall survival. RESULTS: A strong p-STAT3
      (tyr705) nuclear staining was observed in 49.3% of HCC lesions, but was reported
      only in 5.8% of the adjacent non-tumorous liver parenchyma (p<0.001). The
      expression of p-STAT3 (tyr705) in HCC lesions was significantly and positively
      correlated with the intratumour MVD (p = 0.002), but not with Ki-67 expression.
      No significant correlation of p-STAT3 (tyr705) was found in addition to
      histological grading (p = 0.019). Multivariate Cox regression analysis showed
      that p-STAT3 (tyr705) expression was a significant predictor of overall survival
      for HCC (p = 0.036), although the Kaplan-Meier survival curves showed no
      significant difference between the high and low p-STAT3 (tyr705) expression
      subgroups. CONCLUSIONS: The results showed that p-STAT3 (tyr705) expression was
      closely correlated with histological grading and intratumour MVD in HCC. Thus,
      the potential role of p-STAT3 (tyr705) in HCC development may be through these
      correlations.

PMID- 16901977
TI  - The role of clinical guidelines in medical negligence litigation: a shift from
      the Bolam standard?

PMID- 16901978
TI  - Prenatal exposure to ultrasound waves impacts neuronal migration in mice.
AB  - Neurons of the cerebral neocortex in mammals, including humans, are generated
      during fetal life in the proliferative zones and then migrate to their final
      destinations by following an inside-to-outside sequence. The present study
      examined the effect of ultrasound waves (USW) on neuronal position within the
      embryonic cerebral cortex in mice. We used a single BrdU injection to label
      neurons generated at embryonic day 16 and destined for the superficial cortical
      layers. Our analysis of over 335 animals reveals that, when exposed to USW for a
      total of 30 min or longer during the period of their migration, a small but
      statistically significant number of neurons fail to acquire their proper position
      and remain scattered within inappropriate cortical layers and/or in the subjacent
      white matter. The magnitude of dispersion of labeled neurons was variable but
      systematically increased with duration of exposure to USW. These results call for
      a further investigation in larger and slower-developing brains of non-human
      primates and continued scrutiny of unnecessarily long prenatal ultrasound
      exposure.

PMID- 16901979
TI  - Topical interests and the mitigation of search engine bias.
AB  - Search engines have become key media for our scientific, economic, and social
      activities by enabling people to access information on the web despite its size
      and complexity. On the down side, search engines bias the traffic of users
      according to their page ranking strategies, and it has been argued that they
      create a vicious cycle that amplifies the dominance of established and already
      popular sites. This bias could lead to a dangerous monopoly of information. We
      show that, contrary to intuition, empirical data do not support this conclusion;
      popular sites receive far less traffic than predicted. We discuss a model that
      accurately predicts traffic data patterns by taking into consideration the
      topical interests of users and their searching behavior in addition to the way
      search engines rank pages. The heterogeneity of user interests explains the
      observed mitigation of search engines' popularity bias.

PMID- 16901980
TI  - Condition and fate of logged forests in the Brazilian Amazon.
AB  - The long-term viability of a forest industry in the Amazon region of Brazil
      depends on the maintenance of adequate timber volume and growth in healthy
      forests. Using extensive high-resolution satellite analyses, we studied the
      forest damage caused by recent logging operations and the likelihood that logged
      forests would be cleared within 4 years after timber harvest. Across 2,030,637
      km2 of the Brazilian Amazon from 1999 to 2004, at least 76% of all harvest
      practices resulted in high levels of canopy damage sufficient to leave forests
      susceptible to drought and fire. We found that 16+/-1% of selectively logged
      areas were deforested within 1 year of logging, with a subsequent annual
      deforestation rate of 5.4% for 4 years after timber harvests. Nearly all logging
      occurred within 25 km of main roads, and within that area, the probability of
      deforestation for a logged forest was up to four times greater than for unlogged
      forests. In combination, our results show that logging in the Brazilian Amazon is
      dominated by highly damaging operations, often followed rapidly by deforestation
      decades before forests can recover sufficiently to produce timber for a second
      harvest. Under the management regimes in effect at the time of our study in the
      Brazilian Amazon, selective logging would not be sustained.

PMID- 16901982
TI  - Distinct signaling profiles of beta1 and beta2 adrenergic receptor ligands toward
      adenylyl cyclase and mitogen-activated protein kinase reveals the
      pluridimensionality of efficacy.
AB  - Drug efficacy is typically considered an intrinsic property of a ligand/receptor
      couple. However, recent observations suggest that efficacy may also be influenced
      by the signaling effectors engaged by a unique receptor. To directly and
      systematically test this possibility, we assessed the ability of a panel of beta
      adrenergic ligands to modulate the activity of two effector systems, the adenylyl
      cyclase (AC) and the mitogen-activated protein kinase (MAPK), via beta(1) and
      beta(2) adrenergic receptors. Although some compounds displayed similar
      efficacies toward the two pathways, others showed complex efficacy profiles. For
      example, compounds that are inverse agonists for the AC activity were found to be
      either agonists, neutral antagonists, or inverse agonists for the MAPK pathway.
      Likewise, agonists for the AC were either agonists or neutral antagonists for
      MAPK. Given this complexity, we propose a Cartesian representation of the
      efficacies that takes into account the activities of the different effectors that
      can be engaged by a given receptor. In addition, compounds considered as
      nonselective for beta(1) and beta(2) adrenergic receptors, based on their binding
      affinities, showed distinct relative efficacy profiles toward AC and MAPK, adding
      a new dimension to the concept of ligand selectivity. Taken together, the results
      suggest that binding of different ligands promote distinct conformational changes
      leading to specific signaling outcomes. Our data therefore clearly illustrate
      that efficacy is a pluridimensional parameter that is not an intrinsic
      characteristic of a ligand/receptor couple. This should have important
      implications for the future design of screening assays used in drug discovery
      campaigns.

PMID- 16901983
TI  - Systematically assessing the influence of 3-dimensional structural context on the
      molecular evolution of mammalian proteomes.
AB  - The 3-dimensional (3D) structural context of amino acid residues in a protein
      could significantly impact the level of selective constraint on the residues.
      Here, by analyzing 767 mammalian proteins, we systematically investigate how
      various 3D structural contexts influence selective constraint. The structural
      contexts we examined include solvent accessibility, secondary structure, and
      intramolecular residue-residue interactions. Through this analysis, we offer
      quantitative information on how 3D structural contexts affect the level of
      selective constraint.

PMID- 16901981
TI  - Neocortical neurogenesis in humans is restricted to development.
AB  - Stem cells generate neurons in discrete regions in the postnatal mammalian brain.
      However, the extent of neurogenesis in the adult human brain has been difficult
      to establish. We have taken advantage of the integration of (14)C, generated by
      nuclear bomb tests during the Cold War, in DNA to establish the age of neurons in
      the major areas of the human cerebral neocortex. Together with the analysis of
      the neocortex from patients who received BrdU, which integrates in the DNA of
      dividing cells, our results demonstrate that, whereas nonneuronal cells turn
      over, neurons in the human cerebral neocortex are not generated in adulthood at
      detectable levels but are generated perinatally.

PMID- 16901984
TI  - In silico predicted robustness of viroid RNA secondary structures. II.
      Interaction between mutation pairs.
AB  - Viroids are plant subviral pathogens whose genomes are constituted by a single
      stranded and covalently closed small RNA molecule that does not encode for any
      protein. Most of the 29 described viroid species fold into a rodlike or quasi
      rodlike structure, whereas a few of them fold as highly branched structures. In a
      previous study, we used RNA thermodynamic secondary structure prediction
      algorithms to compare the mutational robustness of all viroid species. Here we
      used the same approach to explore the sign and strength of epistasis among pairs
      of random mutations. We found that antagonistic interactions were more abundant
      than synergistic ones. However, despite their lower frequency, synergistic
      interactions tended to be more intense. Mutational robustness and the intensity
      of epistasis were correlated such that viroid species with large average
      mutational effects showed stronger antagonistic epistasis, whereas viroids with
      mild average mutational effects showed weaker antagonistic interactions. The
      strength of antagonistic epistasis decreased with genome complexity as a
      consequence of the gained robustness of duplicated genomes. In good agreement
      with our previous finding of an evolutionary trend toward increased robustness,
      we now found a trend toward reduced antagonistic epistasis.

PMID- 16901985
TI  - A roadmap of tandemly arrayed genes in the genomes of human, mouse, and rat.
AB  - Tandemly arrayed genes (TAGs) play an important functional and physiological role
      in the genome. Most previous studies have focused on individual TAG families in a
      few species, yet a broad characterization of TAGs is not available. Here we
      identified all TAGs in the genomes of humans, mouse, and rat and performed a
      comprehensive analysis of TAG distribution, TAG sizes, TAG orientations and
      intergenic distances, and TAG functions. TAGs account for about 14-17% of all
      genes in the genome and nearly one-third of all duplicated genes, highlighting
      the predominant role that tandem duplication plays in gene duplication. For all
      species, TAG distribution is highly heterogeneous along chromosomes and some
      chromosomes are enriched with TAG forests, whereas others are enriched with TAG
      deserts. The majority of TAGs are of size 2 for all genomes, similar to the
      previous findings in Caenorhabditis elegans, Arabidopsis thaliana, and Oryza
      sativa, suggesting that it is a rather general phenomenon in eukaryotes. The
      comparison with the genome patterns shows that TAG members have a significantly
      higher proportion of parallel gene orientation in all species, corroborating
      Graham's claim that parallel orientation is the preferred form of orientation in
      TAGs. Moreover, TAG members with parallel orientation tend to be closer to each
      other than all neighboring genes in the genome with parallel orientation. The
      analyses of Gene Ontology function indicate that genes with receptor or binding
      activities are significantly overrepresented by TAGs. Computer simulation reveals
      that random gene rearrangements have little effect on the statistics of TAGs for
      all genomes. Finally, the average proportion of TAGs shows a trend of increase
      with the increase of family sizes, although the correlation between TAG
      proportions in individual families and family sizes is not significant.

PMID- 16901986
TI  - High resolution analysis and phylogenetic network construction using complete
      mtDNA sequences in sardinian genetic isolates.
AB  - For mitochondrial phylogenetic analysis, the best result comes from complete
      sequences. We therefore decided to sequence the entire mitochondrial DNA (mtDNA)
      (coding and D-loop regions) of 63 individuals selected in 3 small Ogliastra
      villages, an isolated area of eastern Sardinia: Talana, Urzulei, and
      Perdasdefogu. We studied at least one individual for each of the most frequent
      maternal genealogical lineages belonging to haplogroups H, V, J, K, T, U, and X.
      We found in our 63 samples, 172 and 69 sequence changes in the coding and in the
      D-loop region, respectively. Thirteen out of 172 sequence changes in the coding
      region are novel. It is our hypothesis that some of them are characteristic of
      the Ogliastra region and/or Sardinia. We reconstructed the phylogenetic network
      of the 63 complete mtDNA sequences for the 3 villages. We also drew a network
      including a large number of European sequences and calculated various indices of
      genetic diversity in Ogliastra. It appears that these small populations remained
      extremely isolated and genetically differentiated compared with other European
      populations. We also identified in our samples a never previously described
      subhaplogroup, U5b3, which seems peculiar to the Ogliastra region.

PMID- 16901987
TI  - A naturally occurring point mutation in the rat aquaporin 5 gene, influencing its
      protein production by and secretion of water from salivary glands.
AB  - A greater than twofold diversity in the expression level of aquaporin 5 (AQP5)
      has been observed in the membrane fraction of the submandibular gland (SMG) in
      Sprague-Dawley rats (Murdiastuti K, Miki O, Yao C, Parvin MN, Kosugi-Tanaka C,
      Akamatsu T, Kanamori N, and Hosoi K. Pflugers Arch 445: 405-412, 2002). In the
      present study, breeding between brother and sister rats was repeated within high
      AQP5 producers and low ones to obtain inbred offspring. High- and low-producer
      rats from 3rd to 18th generations were used for experiments. By Western blotting,
      levels of AQP5 proteins in the parotid and lacrimal glands, and lungs were all
      low in low producers, whereas they were all high in high producers, implying
      genetic variations of the gene for this water channel. Despite this implication,
      AQP5 mRNA levels were almost the same between the two groups by Northern
      blotting, suggesting the irrelevance of transcriptional regulation for this
      diversity. AQP5 cDNAs from the SMGs of the two groups were sequenced. The
      nucleotide sequence of AQP5 cDNA from low producers indicated the existence of a
      point mutation at nt 308 (G308A), leading to a replacement of (103)Gly with
      (103)Asp in the third transmembrane domain, but no alteration was detected in the
      Kozak area. The existence of such a mutation was confirmed by the assessment of
      genomic DNA also. This mutation may have resulted in an abnormal membrane
      insertion or ineffective trafficking of AQP5, since the rats having this mutation
      showed extremely low membrane expression of AQP5 in the SMG acinar cells and
      decreased water secretion from their salivary glands.

PMID- 16901988
TI  - Lactobacillus casei prevents the upregulation of ICAM-1 expression and leukocyte
      recruitment in experimental colitis.
AB  - Lactobacillus casei has been shown to attenuate the severity of experimental
      colitis. The objective of the present study was to determine whether the effects
      of L. casei on colitis are related to modulation of leukocyte recruitment into
      the inflamed intestine. Rats with a colonic segment excluded from fecal transit
      were surgically prepared. The segment was decontaminated with antibiotics and
      recolonized with normal flora isolated from the inflamed rat colon, associated or
      not to L. casei. Control and colitic [2,4,6-trinitrobenzenesulfonic acid (TNBS)
      induced] animals were studied. Leukocyte-endothelial cell interactions were
      characterized in the colonic microcirculation by intravital microscopy, and ICAM
      1 and VCAM-1 expression was measured by the radiolabeled antibody technique.
      Compared with the noninflamed colonic segment, induction of colitis by TNBS
      provoked a marked increase in the number of leukocytes firmly adherent to the
      venular wall (0.5 +/- 0.1 vs. 2.1 +/- 0.6 leukocytes/100 mum, P < 0.01).
      Colonization with L. casei significantly reduced the number of adherent
      leukocytes (1.3 +/- 0.4 leukocytes/100 mum; P < 0.05) but did not affect the
      increased rolling interactions associated with the induction of colitis. Compared
      with the noncolitic group, induction of colitis was associated with a marked
      increase in ICAM-1 expression (117 +/- 4 vs. 180 +/- 3 ng antibody/g tissue) that
      was abrogated when the colitic segment was colonized by L. casei (117 +/- 3 ng
      antibody/g tissue, P < 0.05). However, L. casei administration did not modify
      VCAM-1 upregulation in colitic animals. L. casei attenuates leukocyte recruitment
      observed in experimental colitis induced by TNBS. This effect is possibly related
      to abrogation of ICAM-1 upregulation.

PMID- 16901989
TI  - Identification of apoptotic genes mediating TGF-beta/Smad3-induced cell death in
      intestinal epithelial cells using a genomic approach.
AB  - Transforming growth factor (TGF)-beta-dependent apoptosis is important in the
      elimination of damaged or abnormal cells from normal tissues in vivo. Previously,
      we have shown that TGF-beta inhibits the growth of rat intestinal epithelial
      (RIE)-1 cells. However, RIE-1 cells are relatively resistant to TGF-beta-induced
      apoptosis due to a low endogenous Smad3-to-Akt ratio. Overexpression of Smad3
      sensitizes RIE-1 cells (RIE-1/Smad3) to TGF-beta-induced apoptosis by altering
      the Smad3-to-Akt ratio in favor of apoptosis. In this study, we utilized a
      genomic approach to identify potential downstream target genes that are regulated
      by TGF-beta/Smad3. Total RNA samples were analyzed using Affymetrix
      oligonucleotide microarrays. We found that TGF-beta regulated 518 probe sets
      corresponding to its target genes. Interestingly, among the known apoptotic genes
      included in the microarray analyses, only caspase-3 was induced, which was
      confirmed by real-time RT-PCR. Furthermore, TGF-beta activated caspase-3 through
      protein cleavage. Upstream of caspase-3, TGF-beta induced mitochondrial
      depolarization, cytochrome c release, and cleavage of caspase-9, which suggests
      that the intrinsic apoptotic pathway mediates TGF-beta-induced apoptosis in RIE
      1/Smad3 cells.

PMID- 16901990
TI  - Prednisolone-induced Ca2+ malabsorption is caused by diminished expression of the
      epithelial Ca2+ channel TRPV6.
AB  - Glucocorticoids, such as prednisolone, are often used in clinic because of their
      anti-inflammatory and immunosuppressive properties. However, glucocorticoids
      reduce bone mineral density (BMD) as a side effect. Malabsorption of Ca2+ in the
      intestine is supposed to play an important role in the etiology of low BMD. To
      elucidate the mechanism of glucocorticoid-induced Ca2+ malabsorption, the present
      study investigated the effect of prednisolone on the expression and activity of
      proteins responsible for active intestinal Ca2+ absorption including the
      epithelial Ca2+ channel TRPV6, calbindin-D(9K), and the plasma membrane ATPase
      PMCA1b. Therefore, C57BL/6 mice received 10 mg/kg body wt prednisolone daily by
      oral gavage for 7 days and were compared with control mice receiving vehicle
      only. An in vivo 45Ca2+ absorption assay indicated that intestinal Ca2+
      absorption was diminished after prednisolone treatment. We showed decreased
      duodenal TRPV6 and calbindin-D(9K) mRNA and protein abundance in prednisolone
      treated compared with control mice, whereas PMCA1b mRNA levels were not altered.
      Importantly, detailed expression studies demonstrated that in mice these Ca2+
      transport proteins are predominantly localized in the first 2 cm of the duodenum.
      Furthermore, serum Ca2+ and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] concentrations
      remained unchanged by prednisolone treatment. In conclusion, these data suggest
      that prednisolone reduces the intestinal Ca2+ absorption capacity through
      diminished duodenal expression of the active Ca2+ transporters TRPV6 and
      calbindin-D(9K) independent of systemic 1,25(OH)2D3.

PMID- 16901991
TI  - Effect of Slc26a6 deletion on apical Cl-/HCO3- exchanger activity and cAMP
      stimulated bicarbonate secretion in pancreatic duct.
AB  - The role of Slc26a6 (PAT1) on apical Cl-/HCO3- exchange and bicarbonate secretion
      in pancreatic duct cells was investigated using Slc26a6 null and wild-type (WT)
      mice. Apical Cl-/HCO3- exchange activity was measured with the pH-sensitive dye
      BCECF in microperfused interlobular ducts. The HCO3(-)-influx mode of apical [Cl
      ]i/[HCO3-]o exchange (where brackets denote concentration and subscripts i and o
      denote intra- and extracellular, respectively) was dramatically upregulated in
      Slc26a6 null mice (P < 0.01 vs. WT), whereas the HCO3(-)-efflux mode of apical
      [Cl-]o/[HCO3-]i exchange was decreased in Slc26a6 null mice (P < 0.05 vs. WT),
      suggesting the unidirectionality of the Slc26a6-mediated HCO3- transport. Fluid
      secretory rate in interlobular ducts were comparable in WT and Slc26a6 null mice
      (P > 0.05). In addition, when pancreatic juice was collected from whole animal in
      basal and secretin-stimulated conditions, neither juice volume nor its pH showed
      differences between WT and Slc26a6 null mice. Semiquantitative RT-PCR
      demonstrated more than fivefold upregulation in Slc26a3 (DRA) expression in
      Slc26a6 knockout pancreas. In conclusion, these results point to the role of
      Slc26a6 in HCO3- efflux at the apical membrane and also suggest the presence of a
      robust Slc26a3 compensatory upregulation, which can replace the function of
      Slc26a6 in pancreatic ducts.

PMID- 16901992
TI  - Identification of key residues that cause differential gallbladder response to
      PACAP and VIP in the guinea pig.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive
      intestinal polypeptide (VIP) have opposite actions on the gallbladder; PACAP
      induces contraction, whereas VIP induces relaxation. Here, we have attempted to
      identify key residues responsible for their interactions with PACAP (PAC1) and
      VIP (VPAC) receptors in the guinea pig gallbladder. We synthesized PACAP-27/VIP
      hybrid peptides and compared their actions on isolated guinea pig gallbladder
      smooth muscle strips using isotonic transducers. [Ala4]- and [Val5]PACAP-27 were
      more potent than PACAP-27 in stimulating the gallbladder. In contrast, [Ala4,
      Val5]- and [Ala4, Val5, Asn9]PACAP-27 induced relaxation similarly to VIP. [Asn9]
      , [Thr11]-, or [Leu13]PACAP-27 had 20-70% contractile activity of PACAP-27,
      whereas [Asn24,Ser25,Ile26]PACAP-27 showed no change in the activity. All VIP
      analogs, including [Gly4,Ile5,Ser9]VIP, induced relaxation. In the presence of a
      PAC1 receptor antagonist, PACAP(6-38), the contractile response to PACAP-27 was
      inhibited and relaxation became evident. RT-PCR analysis revealed abundant
      expressions of PAC1 receptor, "hop" splice variant, and VPAC1 and VPAC2 receptor
      mRNAs in the guinea pig gallbladder. In conclusion, PACAP-27 induces contraction
      of the gallbladder via PAC1/hop receptors. Gly4 and Ile5 are the key NH2-terminal
      residues of PACAP-27 that distinguish PAC1/hop receptors from VPAC1/VPAC2
      receptors. However, both the NH2-terminal and alpha-helical regions of PACAP-27
      are required for initiating gallbladder contraction.

PMID- 16901993
TI  - Recognition of intestinal epithelial HIF-1alpha activation by Pseudomonas
      aeruginosa.
AB  - Human intestinal epithelial cell monolayers (Caco-2) subjected to hypoxia and
      reoxygenation release soluble factors into the apical medium that activate the
      virulence of the opportunistic pathogen Pseudomonas aeruginosa to express the
      potent barrier-dysregulating protein PA-I lectin/adhesin. In this study, we
      defined the role of hypoxia-inducible factor (HIF)-1alpha in this response. We
      tested the ability of medium from Caco-2 cells with forced expression of HIF
      1alpha to increase PA-I expression in P. aeruginosa and found that medium from
      Caco-2 cells overexpressing HIF-1alpha increased PA-I expression compared with
      medium from control cells (P < 0.001, ANOVA). To identify the components
      responsible for this response, medium was fractionated by molecular weight and
      subjected to mass spectroscopy, which identified adenosine as the possible
      mediator. Both adenosine and its immediate downstream metabolite inosine induced
      PA-I expression in P. aeruginosa in a dose-dependent fashion. Because inosine was
      not detectable in the medium of Caco-2 cells exposed to hypoxia or overexpressing
      HIF-1alpha, we hypothesized that P. aeruginosa itself might metabolize adenosine
      to inosine. Using mutant and parental strains of P. aeruginosa, we demonstrated
      that P. aeruginosa metabolized adenosine to inosine via adenosine deaminase and
      that the conditioned medium enhanced the extracellular accumulation of inosine.
      Together, these results provide evidence that P. aeruginosa can recognize and
      respond to extracellular end products of intestinal hypoxia that are released
      after activation of HIF-1alpha. The ability of P. aeruginosa to metabolize
      adenosine to inosine may represent a subversive microbial virulence strategy that
      deprives the epithelium of the cytoprotective actions of adenosine.

PMID- 16901994
TI  - Induction of cell cycle arrest and apoptosis in HT-29 human colon cancer cells by
      the dietary compound luteolin.
AB  - Luteolin is 3',4',5,7-tetrahydroxyflavone found in celery, green pepper, and
      perilla leaf that inhibits tumorigenesis in animal models. We examined luteolin
      mediated regulation of cell cycle progression and apoptosis in the HT-29 human
      colon cancer cell line. Luteolin decreased DNA synthesis and viable HT-29 cell
      numbers in a concentration-dependent manner. It inhibited cyclin-dependent kinase
      (CDK)4 and CDK2 activity, resulting in G1 arrest with a concomitant decrease of
      phosphorylation of retinoblastoma protein. Activities of CDK4 and CDK2 decreased
      within 2 h after luteolin treatment, with a 38% decrease in CDK2 activity (P <
      0.05) observed in cells treated with 40 micromol/l luteolin. Luteolin inhibited
      CDK2 activity in a cell-free system, suggesting that it directly inhibits CDK2.
      Cyclin D1 levels decreased after luteolin treatment, although no changes in
      expression of cyclin A, cyclin E, CDK4, or CDK2 were detected. Luteolin also
      promoted G2/M arrest at 24 h posttreatment by downregulating cyclin B1 expression
      and inhibiting cell division cycle (CDC)2 activity. Luteolin promoted apoptosis
      with increased activation of caspases 3, 7, and 9 and enhanced poly(ADP-ribose)
      polymerase cleavage and decreased expression of p21(CIP1/WAF1), survivin, Mcl-1,
      Bcl-x(L), and Mdm-2. Decreased expression of these key antiapoptotic proteins
      could contribute to the increase in p53-independent apoptosis that was observed
      in HT-29 cells. We demonstrate that luteolin promotes both cell cycle arrest and
      apoptosis in the HT-29 colon cancer cell line, providing insight about the
      mechanisms underlying its antitumorigenic activities.

PMID- 16901995
TI  - Stress signaling pathways activated by weaning mediate intestinal dysfunction in
      the pig.
AB  - Weaning in the piglet is a stressful event associated with gastrointestinal
      disorders and increased disease susceptibility. Although stress is thought to
      play a role in postweaning intestinal disease, the mechanisms by which stress
      influences intestinal pathophysiology in the weaned pig are not understood. The
      objectives of these experiments were to investigate the impact of weaning on
      gastrointestinal health in the pig and to assess the role of stress signaling
      pathways in this response. Nineteen-day-old pigs were weaned, and mucosal barrier
      function and ion transport were assessed in jejunal and colonic tissues mounted
      on Ussing chambers. Weaning caused marked disturbances in intestinal barrier
      function, as demonstrated by significant (P < 0.01) reductions in transepithelial
      electrical resistance and increases in intestinal permeability to [3H]mannitol in
      both the jejunum and colon compared with intestinal tissues from age-matched,
      unweaned control pigs. Weaned intestinal tissues exhibited increased intestinal
      secretory activity, as demonstrated by elevated short-circuit current that was
      sensitive to treatment with tetrodotoxin and indomethacin, suggesting activation
      of enteric neural and prostaglandin synthesis pathways in weaned intestinal
      tissues. Western blot analyses of mucosal homogenates showed increased expression
      of corticotrophin-releasing factor (CRF) receptor 1 in the jejunum and colon of
      weaned intestinal tissues. Pretreatment of pigs with the CRF receptor antagonist
      alpha-helical CRF(9-41), which was injected intraperitoneally 30 min prior to
      weaning, abolished the stress-induced mucosal changes. Our results indicate that
      weaning stress induces mucosal dysfunction mediated by intestinal CRF receptors
      and activated by enteric nerves and prostanoid pathways.

PMID- 16901996
TI  - Bile acid-induced secretion in polarized monolayers of T84 colonic epithelial
      cells: Structure-activity relationships.
AB  - Bile acid epimers and side-chain homologues are present in the human colon. To
      test whether such bile acids possess secretory activity, cultured T84 colonic
      epithelial cells were used to quantify the secretory properties of synthetic
      epimers and homologues of deoxycholic acid (DCA) and chenodeoxycholic acid
      (CDCA). In our study, chloride secretion was measured as changes in short-circuit
      current (DeltaI(sc), in microA/cm2) with the use of voltage-clamped monolayers of
      T84 cells mounted in Ussing chambers. Bile acids were added at 0.5 mM, a
      concentration that did not alter transepithelial resistance. Data were expressed
      as peak DeltaI(sc) (means +/- SD). When added bilaterally, DCA stimulated a
      DeltaI(sc) response of 15.7 +/- 12.5 microA/cm2. The 12beta-OH epimer of DCA was
      less potent (DeltaI(sc) = 8.0 +/- 1.7 microA/cm2), whereas its 3beta-OH epimer
      had no effect. CDCA stimulated secretion (DeltaI(sc) = 8.2 +/- 5.5 microA/cm2),
      whereas both its 7beta-OH and 3beta-OH epimers were inactive, as was lithocholic
      acid. HomoDCA (1 additional side-chain carbon) was active (DeltaI(sc) = 7.8 +/-
      4.8 microA/cm2), whereas norDCA (1 fewer carbon) and dinorDCA (2 fewer carbons)
      were not. Taurine conjugates of DCA and CDCA stimulated secretion (DeltaI(sc) =
      12.3 +/- 7.5 and 8.8 +/- 4.8 microA/cm2, respectively) from the basolateral side
      but not the apical side. Uptake of taurine conjugates from the basolateral but
      not the apical side was shown by mass spectrometry. These studies indicate marked
      structural specificity for bile acid-induced chloride secretion and show that
      modification of bile acid structure by colonic bacteria modulates the secretory
      properties of these endogenous secretagogues.

PMID- 16901997
TI  - Notification that new names and new combinations have appeared in volume 56, part
      5, of the IJSEM.
AB  - This listing of names published in a previous issue of the IJSEM is provided as a
      service to bacteriology to assist in the recognition of new names and new
      combinations. This procedure was proposed by the Judicial Commission [Minute
      11(ii), Int J Syst Bacteriol 41 (1991), p. 185]. The names given herein are
      listed according to the Rules of priority (i.e. page number and order of valid
      publication of names in the original articles). Taxonomic opinions included in
      this List (i.e. the creation of synonyms or the emendation of circumscriptions)
      cannot be considered as validly published nor, in any other way, approved by the
      International Committee on Systematics of Prokaryotes and its Judicial
      Commission.

PMID- 16901998
TI  - Lactobacillus durianis Leisner et al. 2002 is a later heterotypic synonym of
      Lactobacillus vaccinostercus Kozaki and Okada 1983.
AB  - The taxonomic status of the species Lactobacillus durianis and Lactobacillus
      vaccinostercus is briefly summarized and experimental evidence concerning their
      similarity is presented. Highly similar 16S rRNA gene sequences (99.8 %
      similarity over 1,523 bp), partial recA gene sequences (99.5 % similarity over
      600 bp) and partial hsp60 gene sequences (99.1 % similarity over 924 bp) suggest
      that the two species are closely related. Moreover, a high DNA-DNA binding level
      (87 %) and similar genomic DNA G+C contents (41-44 mol% for both species) as well
      as similar biochemical characteristics support the evidence that they constitute
      a single species. Consequently, according to Rules 38 and 42 of the
      Bacteriological Code, the name Lactobacillus vaccinostercus, the oldest
      legitimate name, must be maintained and the name Lactobacillus durianis should be
      considered a later heterotypic synonym.

PMID- 16901999
TI  - Sulfurimonas paralvinellae sp. nov., a novel mesophilic, hydrogen- and sulfur
      oxidizing chemolithoautotroph within the Epsilonproteobacteria isolated from a
      deep-sea hydrothermal vent polychaete nest, reclassification of Thiomicrospira
      denitrificans as Sulfurimonas denitrificans comb. nov. and emended description of
      the genus Sulfurimonas.
AB  - A novel mesophilic bacterium, strain GO25(T), was isolated from a nest of
      hydrothermal vent polychaetes, Paralvinella sp., at the Iheya North field in the
      Mid-Okinawa Trough. Cells were motile short rods with a single polar flagellum.
      Growth was observed between 4 and 35 degrees C (optimum 30 degrees C; 13-16 h
      doubling time) and between pH 5.4 and 8.6 (optimum pH 6.1). The isolate was a
      facultatively anaerobic chemolithoautotroph capable of growth using molecular
      hydrogen, elemental sulfur or thiosulfate as the sole energy source, carbon
      dioxide as the sole carbon source, ammonium or nitrate as the sole nitrogen
      source and elemental sulfur, thiosulfate or yeast extract as the sole sulfur
      source. Strain GO25(T) represents the first deep-sea epsilonproteobacterium
      capable of growth by both hydrogen and sulfur oxidation. Nitrate or molecular
      oxygen (up to 10 % partial pressure) could serve as the sole electron acceptor to
      support growth. Metabolic products of nitrate reduction shifted in response to
      the electron donor provided. The G+C content of genomic DNA was 37.6 mol%.
      Phylogenetic analysis based on 16S rRNA gene sequences indicated that the novel
      isolate belonged to the genus Sulfurimonas and was most closely related to
      Sulfurimonas autotrophica OK10(T) (96.3 % sequence similarity). DNA-DNA
      hybridization demonstrated that the novel isolate could be differentiated
      genotypically from Sulfurimonas autotrophica OK10(T). On the basis of the
      physiological and molecular properties of the novel isolate, the name
      Sulfurimonas paralvinellae sp. nov. is proposed, with strain GO25(T) (=JCM
      13212(T)=DSM 17229(T)) as the type strain. Thiomicrospira denitrificans DSM
      1251(T) (=ATCC 33889(T)) is phylogenetically associated with Sulfurimonas
      autotrophica OK10(T) and Sulfurimonas paralvinellae GO25(T). Based on the
      phylogenetic relationship between Thiomicrospira denitrificans DSM 1251(T),
      Sulfurimonas autotrophica OK10(T) and Sulfurimonas paralvinellae GO25(T), we
      propose the reclassification of Thiomicrospira denitrificans as Sulfurimonas
      denitrificans comb. nov. (type strain DSM 1251(T)=ATCC 33889(T)). In addition, an
      emended description of the genus Sulfurimonas is proposed.

PMID- 16902000
TI  - Bacillus safensis sp. nov., isolated from spacecraft and assembly-facility
      surfaces.
AB  - Thirteen strains of a novel spore-forming, Gram-positive, mesophilic
      heterotrophic bacterium were isolated from spacecraft surfaces (Mars Odyssey
      Orbiter) and assembly-facility surfaces at the Jet Propulsion Laboratory in
      California and the Kennedy Space Center in Florida. Phylogenetic analysis of 16S
      rRNA gene sequences has placed these novel isolates within the genus Bacillus,
      the greatest sequence similarity (99.9 %) being found with Bacillus pumilus.
      However, these isolates share a mere 91.2 % gyrB sequence similarity with
      Bacillus pumilus, rendering their 16S rRNA gene-derived relatedness suspect.
      Furthermore, DNA-DNA hybridization showed only 54-66 % DNA relatedness between
      the novel isolates and strains of B. pumilus. rep-PCR fingerprinting and
      previously reported matrix-assisted laser desorption/ionization time-of-flight
      mass spectrometry protein profiling clearly distinguished these isolates from B.
      pumilus. Phenotypic analyses also showed some differentiation between the two
      genotypic groups, although the fatty acid compositions were almost identical. The
      polyphasic taxonomic studies revealed distinct clustering of the tested strains
      into two distinct species. On the basis of phenotypic characteristics and the
      results of phylogenetic analyses of 16S rRNA and gyrB gene sequences, repetitive
      element primer-PCR fingerprinting and DNA-DNA hybridization, the 13 isolates
      represent a novel species of the genus Bacillus, for which the name Bacillus
      safensis sp. nov. is proposed. The type strain is FO-36b(T) (=ATCC BAA
      1126(T)=NBRC 100820(T)).

PMID- 16902001
TI  - Catenulispora acidiphila gen. nov., sp. nov., a novel, mycelium-forming
      actinomycete, and proposal of Catenulisporaceae fam. nov.
AB  - A novel, Gram-positive bacterial strain was isolated from forest soil. Among
      species with validly published names, the 16S rRNA gene sequence is related most
      closely (approx. 93 % similarity) to that of Sporichthya polymorpha DSM 43042(T).
      However, differently from this species, it forms both vegetative and aerial
      mycelia. The aerial hyphae are straight to slightly flexuous, starting to septate
      to form chains of more than 20 cylindrical spores with a rugose surface. The
      strain is acidophilic, with a pH range for robust growth between 4.3 and 6.8 and
      an optimum around 6.0. The peptidoglycan type is A3gamma ll-Dpm-Gly. The polar
      lipids are phosphatidylglycerol, diphosphatidylglycerol, phosphatidylinositol,
      phosphatidylinositol mannosides and two unknown phospholipids. Predominant
      menaquinones are MK-9(H(6)) and -9(H(4)), and iso- and anteiso-branched C(16 : 0)
      and C(17 : 0) are the main cellular fatty acids. The DNA G+C content is 71.9
      mol%. The distinct phylogenetic position and the unusual combination of
      chemotaxonomic characteristics justify the proposal of Catenulispora gen. nov.,
      with the type species Catenulispora acidiphila sp. nov. (type strain, ID139908(T)
      =DSM 44928(T)=NRRL B-24433(T)). Catenulisporaceae fam. nov. is also proposed.

PMID- 16902002
TI  - Actinospica robiniae gen. nov., sp. nov. and Actinospica acidiphila sp. nov.:
      proposal for Actinospicaceae fam. nov. and Catenulisporinae subord. nov. in the
      order Actinomycetales.
AB  - Two novel Gram-positive, acidophilic bacterial strains were isolated from forest
      soil. According to their 16S rRNA gene sequences, these strains are related
      closely to each other and form a distinct cluster within the order
      Actinomycetales. They show the typical features of filamentous actinomycetes,
      with branched vegetative hyphae and production of aerial hyphae. The distinct
      phylogenetic positions and the combination of chemotaxonomic characteristics of
      these strains justify the proposal of Actinospica gen. nov. Both strains display
      3-hydroxydiaminopimelic acid plus traces of meso-diaminopimelic acid, the
      phospholipids diphosphatidylglycerol, phosphatidylethanolamine,
      methylphosphatidylethanolamine and phosphatidylinositol, the predominant cellular
      fatty acids i-C(15 : 0), i-C(16 : 0) and ai-C(15 : 0) and the whole-cell sugars
      mannose and rhamnose. They differ in the fatty acid profiles, in the quantitative
      ratios of the major menaquinones MK-9(H(4)), MK-9(H(6)) and MK-9(H(8)) and in the
      occurrence of additional whole-cell sugars (arabinose and xylose in strain
      GE134766(T) and galactose in strain GE134769(T)). Differences in the phenotypic
      characteristics and in the 16S rRNA gene sequences suggest the description of two
      species, Actinospica robiniae gen. nov., sp. nov. (the type species) and
      Actinospica acidiphila sp. nov., with the type strains GE134769(T) (=DSM
      44927(T)=NRRL B-24432(T)) and GE134766(T) (=DSM 44926(T)=NRRL B-24431(T)),
      respectively. The DNA G+C contents of strains GE134769(T) and GE134766(T) are
      70.8 and 69.2 mol%, respectively. Due to the large phylogenetic distance from
      known actinomycete genera, it is proposed to accommodate Actinospica gen. nov. in
      Actinospicaceae fam. nov. In addition, Catenulisporineae subord. nov. is proposed
      to harbour Actinospicaceae fam. nov. and the newly proposed family
      Catenulisporaceae, described in the accompanying paper.

PMID- 16902003
TI  - Rhodanobacter spathiphylli sp. nov., a gammaproteobacterium isolated from the
      roots of Spathiphyllum plants grown in a compost-amended potting mix.
AB  - Three Gram-negative, yellow-pigmented strains were isolated from the rhizospheres
      of Spathiphyllum plants grown in a compost-amended potting mix. The strains
      showed biological control activity towards the root-rot plant pathogen
      Cylindrocladium spathiphylli, and were characterized to determine their taxonomic
      position. Cells of the strains were non-motile rods, and the strains were oxidase
      and catalase-positive and unable to ferment most sugars tested. The three
      strains showed differences in growth temperature range, optimal growth
      temperature and some biochemical reactions. The majority of the fatty acids were
      branched, and large amounts of 15 : 0 iso and 17 : 1 iso omega9c were present.
      The 16S rRNA gene sequence (1,497 bp) of strain B39(T) showed the highest level
      of similarity (98.5 %) to that of Rhodanobacter fulvus IAM 15025(T), followed by
      Rhodanobacter lindaniclasticus LMG 18385(T) (96.0 %; strain no longer extant),
      Dyella koreensis CCUG 50883(T) (96.4 %), Dyella japonica DSM 16301(T) (96.3 %),
      Frateuria aurantia LMG 1558(T) (96.2 %) and Fulvimonas soli LMG 19981(T) (95.9
      %). Less than 90 % 16S rRNA gene sequence similarity was observed for other
      members of the Gammaproteobacteria. The mean DNA-DNA reassociation value for the
      three strains was 100 % and was 25 % when the strains were compared with DNA from
      R. fulvus LMG 23003(T). The strains had a mean DNA G+C content of 67.6 mol%. On
      the basis of their phylogenetic, genomic and phenotypic properties, the three
      strains represent a novel species within the genus Rhodanobacter, for which the
      name Rhodanobacter spathiphylli sp. nov. is proposed. The type strain is strain
      B39(T) (=LMG 23181(T)=DSM 17631(T)).

PMID- 16902004
TI  - Chitinimonas koreensis sp. nov., isolated from greenhouse soil in Korea.
AB  - Strain R2A43-10(T) was isolated from a greenhouse soil in Korea. Cells were Gram
      negative rods, motile by means of a single flagellum. Growth occurred at 10-40
      degrees C and at pH 5-8. Ubiquinone-8 (Q-8) was the only respiratory lipoquinone.
      Major fatty acids were summed feature 3 (C(16 : 1)omega7c and/or iso-C(15 : 0) 2
      OH) and C(16 : 0). 16S rRNA gene sequence analysis revealed that strain R2A43
      10(T) was closely related to Chitinimonas taiwanensis cf(T) (sequence similarity
      of 94.8 %), but it exhibited low sequence similarities (<92 %) to other members
      of the Betaproteobacteria. The G+C content of the genomic DNA of strain R2A43
      10(T) was 65.0 mol%. The novel isolate could be differentiated from C.
      taiwanensis cf(T) by several physiological properties. On the basis of genomic
      and phenotypic data, it is concluded that R2A43-10(T) (=KACC 11467(T)=DSM
      17726(T)) is the type strain of a novel species of the genus Chitinimonas, for
      which the name Chitinimonas koreensis sp. nov. is proposed.

PMID- 16902005
TI  - Herminiimonas arsenicoxydans sp. nov., a metalloresistant bacterium.
AB  - An arsenite-oxidizing bacterium, designated strain ULPAs1(T), was isolated from
      industrial sludge heavily contaminated with arsenic. Cells of this isolate were
      Gram-negative, curved rods, motile by means of a polar flagellum. The strain was
      positive for oxidase and catalase activities, was able to reduce nitrate to
      nitrite, used acetate, lactate and peptone as organic carbon sources under
      aerobic conditions and was able to oxidize arsenite (As[III]) to arsenate
      (As[V]). 16S rRNA gene sequence analysis and the absence of dodecanoic fatty
      acids suggested that this strain represents a member of the genus Herminiimonas
      of the family Oxalobacteraceae, order Burkholderiales in the Betaproteobacteria.
      Genomic DNA-DNA hybridization between strain ULPAs1(T) and Herminiimonas
      fonticola S-94(T) and between strain ULPAs1(T) and Herminiimonas aquatilis CCUG
      36956(T) revealed levels of relatedness of <10 %, well below the recommended 70 %
      species cut-off value. Thus, strain ULPAs1(T) (=CCM 7303(T)=DSM 17148(T)=LMG
      22961(T)) is the type strain of a novel species of Herminiimonas, for which the
      name Herminiimonas arsenicoxydans sp. nov. is proposed.

PMID- 16902006
TI  - Chryseobacterium taiwanense sp. nov., isolated from soil in Taiwan.
AB  - Among a large collection of Taiwanese soil isolates, a novel Gram-negative, rod
      shaped, non-spore-forming, yellow-pigmented bacterial strain, Soil-3-27(T), was
      isolated from farmland soil in Wu-Feng, Taiwan. The isolate was subjected to a
      polyphasic study including 16S rRNA gene sequencing, DNA-DNA hybridization, fatty
      acid analysis and comparative phenotypic characterization. The 16S rRNA gene
      sequence analysis indicated that the organism belongs to the genus
      Chryseobacterium. The organism contains menaquinone MK-6 as the predominant
      isoprenoid quinone and 15 : 0 iso (43 %), 17 : 1 isoomega9c (17.5 %) and 17 : 0
      iso 3-OH (16.6 %) as the major fatty acids. Phylogenetically, the closest
      relatives of strain Soil-3-27(T) are Chryseobacterium daecheongense,
      Chryseobacterium defluvii and Chryseobacterium taichungense with 96.7-97.2 %
      sequence similarity. DNA-DNA hybridization showed relatedness values of 8.5-24.2
      % with these species. The DNA G+C content is 36.8 mol%. Strain Soil-3-27(T) is
      clearly distinguishable from other Chryseobacterium species and represents a
      novel species, for which the name Chryseobacterium taiwanense sp. nov. is
      proposed. The type strain is strain Soil-3-27(T) (=BCRC 17412(T)=IAM 15317(T)=LMG
      23355(T)).

PMID- 16902007
TI  - Niastella koreensis gen. nov., sp. nov. and Niastella yeongjuensis sp. nov.,
      novel members of the phylum Bacteroidetes, isolated from soil cultivated with
      Korean ginseng.
AB  - Two novel strains, GR20-10(T) and GR20-13(T), were isolated from soil using R2A
      medium. The soil sample was collected from a field in the Yeongju region of Korea
      that was cultivated with Korean ginseng. Phylogenetic analysis based on 16S rRNA
      gene sequences indicated that these strains formed a cluster with several
      uncultured bacterial clones and with Flexibacter filiformis, Flexibacter sancti,
      Flexibacter japonensis, Cytophaga arvensicola and Flavobacterium ferrugineum
      (recently reclassified as Terrimonas ferruginea) in the phylum Bacteroidetes. The
      level of 16S rRNA gene sequence similarity between the two novel strains was 98.9
      %. Isolates GR20-10(T) and GR20-13(T) showed the highest sequence similarities to
      Flexibacter japonensis IFO 16041(T) (91.8 and 91.9 %, respectively) and T.
      ferruginea ATCC 13524(T) (90.4 and 90.6 %, respectively). The whole-cell fatty
      acid profiles of the two isolates were similar and their major fatty acids were
      15 : 0 iso, 17 : 0 iso 3-OH and 15 : 1 iso G. The major isoprenoid quinone of
      both strains was MK-7. The G+C contents of GR20-10(T) and GR20-13(T) were 45.8
      and 44.3 mol%, respectively. DNA-DNA hybridization (57 % DNA-DNA hybridization
      value) and phenotypic data indicated that strains GR20-10(T) and GR20-13(T) each
      belong to a separate species. On the basis of phenotypic and phylogenetic data
      and genomic distinctiveness, strains GR20-10(T) and GR20-13(T) represent two
      novel species in a novel genus in the phylum Bacteroidetes; the names Niastella
      koreensis gen. nov., sp. nov. (the type species; type strain GR20-10(T)=KACC
      11465(T)=DSM 17620(T)) and Niastella yeongjuensis sp. nov. (type strain GR20
      13(T)=KACC 11466(T)=DSM 17621(T)) are proposed.

PMID- 16902008
TI  - Nocardioides kongjuensis sp. nov., an N-acylhomoserine lactone-degrading
      bacterium.
AB  - A Gram-positive, rod- or coccoid-shaped and N-hexanoyl-l-homoserine lactone
      degrading bacterial strain, A2-4(T), was isolated from a soil in Korea, and its
      taxonomic position was investigated by using a polyphasic approach. Strain A2
      4(T) grew optimally at pH 7.0-8.0 and 30 degrees C without NaCl. Phylogenetic
      analyses based on 16S rRNA gene sequences revealed that strain A2-4(T) is most
      closely related to members of the genus Nocardioides. Strain A2-4(T) possessed
      chemotaxonomic properties indicative of members of the genus Nocardioides; the
      cell-wall peptidoglycan type was based on ll-diaminopimelic acid, MK-8(H(4)) was
      the predominant menaquinone and iso-C(16 : 0) was the predominant fatty acid. The
      DNA G+C content was 72.1 mol%. The 16S rRNA gene sequence of strain A2-4(T) was
      98.3-99.1 % similar to those of the type strains of Nocardioides simplex,
      Nocardioides aromaticivorans and Nocardioides nitrophenolicus and 93.8-96.3 %
      similar to those of the type strains of other Nocardioides species. Strain A2
      4(T) could be distinguished from the three phylogenetic relatives, N.
      nitrophenolicus, N. aromaticivorans and N. simplex, by DNA-DNA relatedness (25-42
      %) and by differences in some phenotypic characteristics. On the basis of the
      phenotypic, phylogenetic and genetic data, the strain represents a novel species
      of the genus Nocardioides, for which the name Nocardioides kongjuensis sp. nov.
      is proposed. The type strain is A2-4(T) (=KCTC 19054(T)=JCM 12609(T)).

PMID- 16902009
TI  - Actinocatenispora thailandica gen. nov., sp. nov., a new member of the family
      Micromonosporaceae.
AB  - Two actinomycete strains, TT2-10(T) and TT2-3, which produced long spore chains
      (more than 10 spores per chain), were isolated from peat swamp forest soil in
      Pattaloong Province, Thailand. Their taxonomic positions were determined using a
      polyphasic approach. The chemotaxonomic characteristics of these strains
      coincided with those of the family Micromonosporaceae, i.e. cell-wall chemotype
      II, muramic acid of the N-glycolyl type, whole-cell sugar pattern D and type II
      phospholipids. Analysis of the 16S rRNA gene sequences also indicated that these
      strains constitute a distinct lineage within the family Micromonosporaceae,
      sharing 91.3-93.8 % sequence similarity with members of this family. On the basis
      of their phenotypic and genotypic characteristics and their phylogenetic
      position, these strains represent a novel genus and species, for which the name
      Actinocatenispora thailandica gen. nov., sp. nov. is proposed. The type strain of
      Actinocatenispora thailandica is strain TT2-10(T) (=JCM 12343(T)=PCU 235(T)=DSM
      44816(T)).

PMID- 16902010
TI  - Gillisia myxillae sp. nov., a novel member of the family Flavobacteriaceae,
      isolated from the marine sponge Myxilla incrustans.
AB  - A yellow-pigmented, Gram-negative, rod-shaped, strictly aerobic bacterium (strain
      UST050418-085(T)) was isolated from the surface of a marine sponge, Myxilla
      incrustans, at Friday Harbor, WA, USA. The DNA G+C content of this strain was
      34.6 mol%. The predominant fatty acids were i15 : 0, a15 : 0, i15 : 1, i16 : 0,
      i17 : 0 3-OH, 17 : 0 2-OH and summed feature 3, comprising i15 : 0 2-OH and/or 16
      : 1omega7c (altogether representing 69.0 % of the total fatty acids). MK-6 was
      the only respiratory quinone detected. Phylogenetic analysis based on 16S rRNA
      gene sequences indicated that the closest relatives of UST050418-085(T) were
      members of the genus Gillisia, with sequence similarities of 93.2-96.6 %. Strain
      UST050418-085(T) differed from its closest relatives by 11 to 18 phenotypic
      traits. Molecular evidence and phenotypic characteristics suggest that strain
      UST050418-085(T) represents a novel species within the genus Gillisia. The name
      Gillisia myxillae sp. nov. is proposed, with UST050418-085(T) (=JCM 13564(T)=NRRL
      B-41416(T)) [corrected] as the type strain.

PMID- 16902011
TI  - Classification of Centers for Disease Control Group Eugonic Fermenter (EF)-4a and
      EF-4b as Neisseria animaloris sp. nov. and Neisseria zoodegmatis sp. nov.,
      respectively.
AB  - A polyphasic taxonomic study was performed on isolates classified as Centers for
      Disease Control Group Eugonic Fermenter (EF)-4a and EF-4b. Comparative 16S rRNA
      gene sequence analysis confirmed that group EF-4a and EF-4b belong to the genus
      Neisseria with Neisseria canis and Neisseria dentiae as the nearest phylogenetic
      neighbours. DNA-DNA hybridizations and biochemical analyses demonstrated that
      isolates of group EF-4a and EF-4b represent two novel species within this
      sublineage of the genus Neisseria. Based on the results of the present study,
      isolates of group EF-4a and EF-4b are classified as Neisseria animaloris sp. nov.
      (type strain LMG 23011(T)=NCTC 12228(T)) and Neisseria zoodegmatis sp. nov. (type
      strain LMG 23012(T)=NCTC 12230(T)), respectively.

PMID- 16902012
TI  - Agrococcus lahaulensis sp. nov., isolated from a cold desert of the Indian
      Himalayas.
AB  - The taxonomic position of a lemon-yellow-pigmented actinobacterium, strain K22
      21(T), isolated from a soil sample from Lahaul-Spiti Valley in the Indian
      Himalayas, was determined using a polyphasic approach. The strain had phenotypic
      and chemical properties that were consistent with its classification in the genus
      Agrococcus. Alignment of the 16S rRNA gene sequence of strain K22-21(T) with
      sequences from Agrococcus jenensis DSM 9580(T), Agrococcus baldri DSM 14215(T)
      and Agrococcus citreus DSM 12453(T) revealed similarities of 98.5, 96.8 and 96.6
      %, respectively. However, the level of DNA-DNA relatedness between strain K22
      21(T) and A. jenensis was 55.1 %. The novel strain could be distinguished from
      type strains of the three species of the genus Agrococcus using DNA-DNA
      relatedness and phenotypic data. Based on these differences, strain K22-21(T)
      (=MTCC 7154(T)=DSM 17612(T)) should be classified as the type strain of a novel
      species of Agrococcus, for which the name Agrococcus lahaulensis sp. nov. is
      proposed.

PMID- 16902013
TI  - Amycolatopsis taiwanensis sp. nov., from soil.
AB  - An actinomycete strain (0345M-7(T)) was isolated from a soil sample from Yilan
      county, Taiwan. The isolate displayed substrate mycelia, upon which were borne
      short spore chains. The spore chains were composed of non-motile, smooth
      surfaced, oval spores. Strain 0345M-7(T) had meso-diaminopimelic acid in its
      peptidoglycan. Whole-cell sugars were galactose, glucose, arabinose and ribose.
      The only phospholipid found was phosphatidylethanolamine. The predominant
      menaquinone was MK-9(H(4)). Mycolic acids were not detected. Major cellular fatty
      acids were iso-C(16 : 0) (38.1 %) and C(17 : 1) (25.4 %). The DNA G+C content of
      strain 0345M-7(T) was 68.9 mol%. On the basis of phenotypic and genotypic data,
      it is proposed that strain 0345M-7(T) (=BCRC 16802(T)=KCTC 19116(T)) should be
      classified as the type strain of a novel species of the genus Amycolatopsis,
      Amycolatopsis taiwanensis sp. nov.

PMID- 16902014
TI  - Gordonia araii sp. nov. and Gordonia effusa sp. nov., isolated from patients in
      Japan.
AB  - Two bacterial strains, IFM 10211(T) and IFM 10200(T), were isolated from the
      sputum of two Japanese patients, and were subjected to a polyphasic taxonomic
      study. The two strains were found to have morphological, physiological and
      chemotaxonomic properties that were consistent with their assignment to the genus
      Gordonia, except for a few chemotaxonomic characteristics. Almost complete 16S
      rRNA gene sequences of the two strains were determined; the data showed that they
      are related distantly to Gordonia amarae, Gordonia hirsuta, Gordonia hydrophobica
      and Gordonia sihwensis, showing 16S rRNA gene sequence similarities to the type
      strains of these species of 96.2-97.9 %. DNA-DNA relatedness data coupled with
      the combination of genotypic and phenotypic data indicated that the two strains
      are representatives of two novel, separate species. The names proposed to
      accommodate these two strains are Gordonia araii sp. nov. (type strain IFM
      10211(T)=DSM 44811(T)=NBRC 100433(T)=JCM 12131(T)) and Gordonia effusa sp. nov.
      (type strain IFM 10200(T)=DSM 44810(T)=NBRC 100432(T)=JCM 12130(T)).

PMID- 16902016
TI  - Pedobacter roseus sp. nov., isolated from a hypertrophic pond, and emended
      description of the genus Pedobacter.
AB  - A Gram-negative, pink-coloured, rod-shaped, non-flagellated bacterium, designated
      CL-GP80(T), was isolated from a hypertrophic pond located within the campus of
      Seoul National University, Korea. Analysis of its 16S rRNA gene sequence revealed
      that strain CL-GP80(T) belongs to the family Sphingobacteriaceae and is closely
      related to Pedobacter heparinus ATCC 13125(T) (95.8 % sequence similarity) and to
      other members of the genus Pedobacter (90.8-95.3 % similarity). Temperature and
      pH ranges for growth were 5-33 degrees C and pH 6-8, respectively. The DNA G+C
      content was 41.3 mol%. The major fatty acids were iso-C(15 : 0) (37.0 %), iso
      C(15 : 0) 2-OH and/or C(16 : 1)omega7c (24.5 %), and iso-C(17 : 0) 3-OH (11.3 %).
      Phenotypic, chemotaxonomic and phylogenetic analyses indicated that strain CL
      GP80(T) could be assigned to the genus Pedobacter, but distinguished from
      recognized species of the genus. Strain CL-GP80(T) (=KCCM 42272(T)=JCM 13399(T))
      is therefore proposed as the type strain of a novel species, for which the name
      Pedobacter roseus sp. nov. is proposed.

PMID- 16902015
TI  - Description of Pseudochrobactrum gen. nov., with the two species
      Pseudochrobactrum asaccharolyticum sp. nov. and Pseudochrobactrum saccharolyticum
      sp. nov.
AB  - Two Gram-negative, rod-shaped, oxidase-positive, non-spore-forming, non-motile
      bacteria (CCUG 46016(T) and CCUG 33852(T)), isolated from a knee aspirate of a 66
      year-old man and an industrial glue, respectively, were studied for their
      taxonomic position. On the basis of chemotaxonomic data [i.e. major ubiquinone (Q
      10), major polar lipids (phosphatidylethanolamine, phosphatidylglycerol and
      phosphatidylcholine) and major fatty acids (C(18 : 1)omega7c and C(19 : 0) cyclo
      omega8c)] and 16S rRNA gene sequence similarity, both strains belong to the
      Alphaproteobacteria. The presence of spermidine and putrescine as the predominant
      polyamines in CCUG 46016(T) were in agreement with its phylogenetic affiliation
      in the vicinity of the genus Ochrobactrum. 16S rRNA gene sequence similarities
      between both strains and established species within the genera Bartonella,
      Ochrobactrum and Brucella were less than 95 %. Although both organisms showed
      highest 16S rRNA gene sequence similarity to members of Brucella, phenotypic
      features (including chemotaxonomic features) were more like those of members of
      the genus Ochrobactrum. Sequence comparison of the recA genes confirmed the
      separate phylogenetic position of the two strains. On the basis of DNA-DNA
      pairing results and physiological and biochemical data, the two strains can be
      clearly differentiated from each other and from all known Ochrobactrum species.
      It is evident that these organisms represent two novel species in a new genus,
      Pseudochrobactrum gen. nov., for which the names Pseudochrobactrum
      asaccharolyticum sp. nov. (the type species, type strain CCUG 46016(T)=CIP
      108977(T)) and Pseudochrobactrum saccharolyticum sp. nov. (type strain CCUG
      33852(T)=CIP 108976(T)) are proposed.

PMID- 16902017
TI  - Haloterrigena longa sp. nov. and Haloterrigena limicola sp. nov., extremely
      halophilic archaea isolated from a salt lake.
AB  - Halophilic archaeal strains ABH32(T) and AX-7(T) were isolated from Aibi salt
      lake in Xin-Jiang, China, and were subjected to taxonomic studies. The cells of
      both strains were rod-shaped, and growth required at least 10 % (w/v) NaCl. The
      cellular polar lipids were identified as phosphatidylglycerol,
      phosphatidylglycerol phosphate methyl ester and mannose-2,6-disulfate (1-->2)
      glucose glycerol diether (S(2)-DGD). The isolates were different in that strain
      ABH32(T) did not require magnesium and had strong ability to assimilate sugars
      for growth, whereas strain AX-7(T) required magnesium and did not assimilate
      glucose, sucrose or maltose for growth. Both strain ABH32(T) and strain AX-7(T)
      were most closely related to members of the genera Haloterrigena and Natrinema.
      On the basis of phenotypic and genotypic characteristics, especially their
      cellular polar lipids, the two isolates were assigned to the genus Haloterrigena.
      Moreover, the DNA relatedness values for strains ABH32(T) and AX-7(T) with
      respect to members of the genus Haloterrigena were found to be well below 70 %.
      Thus, strains ABH32(T) and AX-7(T) represent two novel species within the genus
      Haloterrigena, for which the names Haloterrigena longa sp. nov. (type strain
      ABH32(T)=CGMCC 1.5334(T)=JCM 13562(T)) and Haloterrigena limicola sp. nov. (type
      strain AX-7(T)=CGMCC 1.5333(T)=JCM 13563(T)) are proposed.

PMID- 16902018
TI  - Paucisalibacillus globulus gen. nov., sp. nov., a Gram-positive bacterium
      isolated from potting soil.
AB  - A Gram-positive bacterium, designated B22(T), was isolated from potting soil
      produced in Portugal. This organism is a catalase-positive, oxidase-negative,
      motile, spore-forming, aerobic rod that grows optimally at 37 degrees C and pH
      8.0-8.5. Optimal growth occurs in media containing 1 % (w/v) NaCl, although the
      organism can grow in 0-8 % NaCl. The cell wall peptidoglycan is of the A4alpha
      type with a cross-linkage containing d-Asp. The major respiratory quinone is
      menaquinone 7 and the major fatty acids are anteiso-15 : 0, anteiso-17 : 0 and
      iso-15 : 0. The DNA G+C content is 37.9 mol%. Phylogenetic analysis of 16S rRNA
      gene sequences revealed that strain B22(T) formed a new branch within the family
      Bacillaceae. The novel isolate is phylogenetically closely related to members of
      genera of moderately halophilic bacilli and formed a coherent cluster with
      species of the genera Salinibacillus, Virgibacillus, Oceanobacillus and
      Lentibacillus, supported by bootstrap analysis at a confidence level of 71 %.
      Strain B22(T) exhibited 16S rRNA gene pairwise sequence similarity values of 94.7
      94.3 % with members of the genus Salinibacillus, 95.1-92.8 % with members of the
      genus Virgibacillus, 94.7-93.2 % with members of the genus Oceanobacillus and
      93.1-92.3 % with members of the genus Lentibacillus. On the basis of phylogenetic
      analysis and physiological and biochemical characteristics, it is proposed that
      strain B22(T) represents a novel species in a new genus, Paucisalibacillus
      globulus gen. nov., sp. nov. Strain B22(T) (=LMG 23148(T)=CIP 108857(T)) is the
      type strain of Paucisalibacillus globulus.

PMID- 16902019
TI  - Burkholderia mimosarum sp. nov., isolated from root nodules of Mimosa spp. from
      Taiwan and South America.
AB  - Fourteen strains were isolated from nitrogen-fixing nodules on the roots of
      plants of the genus Mimosa growing in Taiwan, Brazil and Venezuela. On the basis
      of 16S rRNA gene sequence similarities, all of the strains were previously shown
      to be closely related to each other and to belong to the genus Burkholderia. A
      polyphasic approach, including DNA-DNA reassociation, whole-cell protein
      analysis, fatty acid methyl ester analysis and extensive biochemical
      characterization, was used to clarify the taxonomic position of these strains:
      all 14 strains were classified as representing a novel species, for which the
      name Burkholderia mimosarum sp. nov. is proposed. The type strain, PAS44(T) (=LMG
      23256(T) =BCRC 17516(T)), was isolated from Mimosa pigra nodules in Taiwan.

PMID- 16902020
TI  - Pedobacter aquatilis sp. nov., isolated from drinking water, and emended
      description of the genus Pedobacter.
AB  - A Gram-negative, rod-shaped, non-spore-forming bacterium (strain AR107(T)) was
      isolated from the drinking water distribution system of Seville (Spain). A
      polyphasic taxonomic study of the isolate resulted in its identification as a
      member of the genus Pedobacter. On the basis of 16S rRNA gene sequence
      comparisons, strain AR107(T) was shown to belong to the phylum Bacteroidetes,
      being related to members of the genus Pedobacter. It showed 95.2 % sequence
      similarity with respect to the type strains of Pedobacter heparinus and
      Pedobacter piscium, and 94.1 % similarity with respect to the type strain of
      Pedobacter himalayensis. The predominant fatty acids were iso-C(15 : 0), iso-C(17
      : 0) 3-OH and summed feature 3 (iso-C(15 : 0) 2-OH and/or C(16 : 1)omega7c),
      which supports the affiliation of strain AR107(T) to the genus Pedobacter. The
      DNA G+C content of this strain was 38 mol%. On the basis of the phenotypic,
      phylogenetic and genotypic results, strain AR107(T) represents a novel species,
      for which the name Pedobacter aquatilis sp. nov. is proposed. The type strain is
      AR107(T) (=CCM 7347(T)=CECT 7114(T)=JCM 13454(T)).

PMID- 16902021
TI  - Lentibacillus halophilus sp. nov., from fish sauce in Thailand.
AB  - Fifteen strains of extremely halophilic bacteria were isolated from fish sauce
      (nam-pla) collected in Thailand at various stages of the fish-fermentation
      process. The isolates were strictly aerobic, spore-forming, Gram-positive rods.
      They grew optimally in the presence of 20-26 % NaCl. The cell-wall peptidoglycan
      contained meso-diaminopimelic acid. The predominant menaquinone was MK-7. The
      major cellular fatty acids were anteiso-C(15 : 0) and anteiso-C(17 : 0). Polar
      lipid analysis revealed the presence of phosphatidylglycerol,
      diphosphatidylglycerol and two unidentified glycolipids. The DNA G+C content was
      42.1-43.1 mol%. On the basis of the 16S rRNA gene sequence, a representative
      strain, PS11-2(T), was found to be closely related to Lentibacillus juripiscarius
      JCM 12147(T) (97.3 % similarity). The 15 strains were included in the same
      species on the basis that the levels of DNA-DNA relatedness with strain PS11-2(T)
      were greater than 70 %. They could be distinguished from L. juripiscarius and
      other Lentibacillus species on the basis of several phenotypic characteristics
      and low levels of DNA-DNA relatedness (</=19.4 %). Therefore, the strains
      represent a novel species of the genus Lentibacillus, for which the name
      Lentibacillus halophilus sp. nov. is proposed. The type strain is PS11-2(T) (=JCM
      12149(T)=TISTR 1549(T)=PCU 240(T)).

PMID- 16902022
TI  - Meganema perideroedes gen. nov., sp. nov., a filamentous alphaproteobacterium
      from activated sludge.
AB  - An industrial wastewater treatment plant at Grindsted, Denmark, has suffered from
      bulking problems for several years caused by filamentous bacteria. Five strains
      were isolated from the sludge by micromanipulation. Phylogenetic analysis of the
      16S rRNA gene sequences showed that the strains formed a monophyletic cluster in
      the Alphaproteobacteria, and they were phenotypically different from their
      closest relatives and from all hitherto known filamentous bacteria described
      (closest relative Brevundimonas vesicularis ATCC 11426(T), 89.8 % sequence
      similarity). In pure culture, the cells (1.5-2.0 microm) in filaments are Gram
      negative and contain polyphosphate and polyhydroxyalkanoates. The optimum
      temperature for growth is 30 degrees C and the strains grow in 2 % NaCl and are
      oxidase- and catalase-positive. Ubiquinone 10 is the major quinone. The major
      fatty acid (C(18 : 1)omega7c) and smaller amounts of unsaturated fatty acids, 3
      hydroxy fatty acids with a chain length of 16 and 18 carbon atoms and small
      amounts of 10-methyl-branched fatty acids with 18 carbon atoms (C(19 : 0) 10
      methyl) affiliated the strains with the Methylobacterium/Xanthobacter group in
      the Alphaproteobacteria. The G+C content of the DNA is 42.9 mol% (for strain
      Gr1(T)). The two most dissimilar isolates by 16S rRNA gene comparison (Gr1(T) and
      Gr10; 97.7 % identical) showed 71.5 % DNA-DNA relatedness. Oligonucleotide probes
      specific for the pure cultures were designed for fluorescence in situ
      hybridization and demonstrated that two filamentous morphotypes were present in
      the Grindsted wastewater treatment plant. It is proposed that the isolates
      represent a new genus and species, Meganema perideroedes gen. nov., sp. nov. The
      type strain of Meganema perideroedes is strain Gr1(T) (=DSM 15528(T)=ATCC BAA
      740(T)).

PMID- 16902023
TI  - Shimia marina gen. nov., sp. nov., a novel bacterium of the Roseobacter clade
      isolated from biofilm in a coastal fish farm.
AB  - A rod-shaped marine bacterium, CL-TA03(T), isolated from a biofilm in a coastal
      fish farm in Tongyeong, Korea, was characterized for physiological and
      biochemical features, fatty acid profile and phylogenetic position based on 16S
      rRNA gene sequences. Analysis of the 16S rRNA gene sequence revealed a clear
      affiliation with the family Rhodobacteraceae. Phylogenetic analysis of the 16S
      rRNA gene sequence showed that the closest relatives of CL-TA03(T) were
      Thalassobius gelatinovorus and Thalassobius mediterraneus (95.6 % similarity).
      The sequence similarities between CL-TA03(T) and other type species of the
      Roseobacter lineage ranged from 92.4 to 95.4 %. Strain CL-TA03(T) is motile and
      grows on marine agar as colourless or beige colonies. The strain is able to grow
      optimally in the range of 3-5 % sea salts. It grows within a temperature range of
      15-35 degrees C and at pH 6-10. The fatty acids are dominated by 18 : 1omega7c
      (64.1 %) and 11-methyl 18 : 1omega7c (10.6 %). The DNA G+C content is 57.2 mol%.
      According to physiological data, fatty acid composition and phylogenetic analysis
      of the 16S rRNA gene sequence, CL-TA03(T) is considered to represent a new genus
      in the family Rhodobacteraceae and the name Shimia marina gen. nov., sp. nov. is
      proposed. The type strain of Shimia marina is CL-TA03(T) (=KCCM 42117(T)=JCM
      13038(T)).

PMID- 16902024
TI  - Pseudomonas peli sp. nov. and Pseudomonas borbori sp. nov., isolated from a
      nitrifying inoculum.
AB  - Sixteen Gram-negative, rod-shaped, non-spore-forming isolates were obtained from
      a nitrifying inoculum. Analysis of repetitive sequence-based PCR and SDS-PAGE
      banding patterns, 16S rRNA gene sequence analysis and DNA-DNA hybridizations
      showed that the isolates belonged to various groups within the genus Pseudomonas.
      One group of isolates could be assigned to Pseudomonas migulae and a second to
      Pseudomonas veronii. Two groups could be differentiated genotypically from each
      other and from all other currently known Pseudomonas species. Analysis of the
      fatty acid composition and physiological and biochemical tests allowed
      differentiation of these groups from their closest phylogenetic neighbours and
      they therefore represent two novel species within the genus Pseudomonas, for
      which the names Pseudomonas peli sp. nov. and Pseudomonas borbori sp. nov. are
      proposed, with strains LMG 23201(T) (=DSM 17833(T)=R-20805(T)) and LMG 23199(T)
      (=DSM 17834(T)=R-20821(T)), respectively, as the type strains.

PMID- 16902025
TI  - Balneola vulgaris gen. nov., sp. nov., a member of the phylum Bacteroidetes from
      the north-western Mediterranean Sea.
AB  - A novel aerobic, Gram-negative bacterium, named 13IX/A01/164(T), was isolated
      from surface waters in the coastal north-western Mediterranean Sea. Cells were
      motile, straight rods, 2.5 mum long and 0.2 mum wide, and formed orange colonies
      on marine agar medium. The G+C content of the genomic DNA of strain
      13IX/A01/164(T) was 42 mol%. Phylogenetic analysis of the 16S rRNA gene sequence
      placed the strain in the phylum Bacteroidetes within the family Crenotrichaceae.
      On the basis of 16S rRNA gene sequence comparison and physiological and
      biochemical characteristics, this isolate represents a novel species of a new
      genus, for which the name Balneola vulgaris gen. nov., sp. nov. is proposed. The
      type strain of Balneola vulgaris is 13IX/A01/164(T) (=DSM 17893(T)=CIP
      109092(T)=OOB 256(T)).

PMID- 16902026
TI  - Brevibacterium samyangense sp. nov., an actinomycete isolated from a beach
      sediment.
AB  - A novel actinomycete, strain SST-8(T), was isolated from sand sediment of Samyang
      Beach in Jeju, Korea, and subjected to a polyphasic taxonomic study. The
      organism, which produced opaque, circular, yellow colonies, with a coryneform
      morphology, showed the following chemotaxonomic characteristics: meso
      diaminopimelic acid as the diamino acid in the peptidoglycan, MK-8(H(2)) as the
      major menaquinone, phosphatidylglycerol as the only polar lipid, anteiso-C(15 :
      0) and anteiso-C(17 : 0) as major fatty acids and a DNA G+C content of 70.7 mol%.
      The combination of morphological and chemotaxonomic features supported its
      classification in the genus Brevibacterium. Phylogenetic analyses, based on 16S
      rRNA gene sequence studies, showed that strain SST-8(T) formed an intermediate
      branch between the Brevibacterium luteolum/Brevibacterium otitidis and
      Brevibacterium mcbrellneri/Brevibacterium paucivorans clusters. Sequence
      similarity calculations based on a neighbour-joining analysis revealed that the
      closest relatives of strain SST-8(T) were the type strains of B. paucivorans
      (96.6 %), B. luteolum (96.5 %), B. mcbrellneri (96.3 %), Brevibacterium avium
      (96.0 %) and B. otitidis (95.9 %). Based on a broad set of phenotypic and genetic
      data, it was evident that the strain represents a novel species of the genus
      Brevibacterium. The name Brevibacterium samyangense sp. nov. is proposed, with
      SST-8(T) (=NRRL B-41420(T)=KCCM 42316(T)) as the type strain.

PMID- 16902027
TI  - Bacillus seohaeanensis sp. nov., a halotolerant bacterium that contains L-lysine
      in its cell wall.
AB  - A halotolerant, round-endospore-forming, aerobic, Gram-positive bacterium,
      designated BH724(T), was isolated from a solar saltern at Taean in Korea. Cells
      of this strain were rod-shaped and found to be non-motile. Strain BH724(T) grew
      at salinities of 0-10 % (w/v) NaCl with an optimum of 3 % (w/v) NaCl and at
      temperatures of 15-50 degrees C with an optimum of 40 degrees C. Phylogenetic
      analyses based on 16S rRNA gene sequences showed that strain BH724(T) belonged to
      the genus Bacillus and that Bacillus aquimaris TF-12(T), Bacillus marisflavi TF
      11(T) and Bacillus vietnamensis JCM 11124(T) were its closest neighbours, sharing
      97.3, 97.2 and 97.0 % 16S rRNA gene sequence similarity, respectively. The
      genomic DNA G+C content was 39 mol% and the predominant menaquinone was MK-7. Its
      major cellular fatty acids were anteiso-C(15 : 0), iso-C(15 : 0), iso-C(16 : 0)
      and iso-C(14 : 0). The peptidoglycan type was A1alpha, linked directly through l
      lysine. On the basis of morphological, chemotaxonomic, physiological and
      phylogenetic properties, strain BH724(T) represents a novel species of the genus
      Bacillus, for which the name Bacillus seohaeanensis sp. nov. is proposed. The
      type strain is BH724(T) (=KCTC 3913(T)=DSM 16464(T)).

PMID- 16902029
TI  - Aeromonas sharmana sp. nov., isolated from a warm spring.
AB  - A Gram-negative, facultatively anaerobic bacterial strain designated GPTSA-6(T)
      was isolated from a water sample collected from a warm spring in Assam, India.
      Preliminary analysis of the 16S rRNA gene sequence of this isolate revealed its
      affiliation to the family Aeromonadaceae. Detailed characterization using a
      polyphasic approach indicated that strain GPTSA-6(T) is most closely related to
      Aeromonas sobria but differs significantly from existing members of the genus
      Aeromonas. Analysis of the almost-complete (1430 nt) 16S rRNA gene sequence of
      this strain revealed that its closest relative (99.23 % similarity) is an
      uncultured bacterial clone, A-8, isolated from an algal bloom. Of the taxa with
      validly published names, Aeromonas sobria ATCC 43979(T) showed the highest level
      of sequence similarity (95.13 %) with respect to strain GPTSA-6(T), followed by
      Aeromonas molluscorum 848T(T) and Aeromonas popoffii LMG 17541(T) (95.04 %
      similarity in both cases). On the basis of the phenotypic, chemotaxonomic and
      phylogenetic data, it can be concluded that strain GPTSA-6(T) represents a novel
      species of the genus Aeromonas, for which the name Aeromonas sharmana sp. nov. is
      proposed. The type strain is GPTSA-6(T) (=MTCC 7090(T)=DSM 17445(T)).

PMID- 16902028
TI  - Novel nitrogen-fixing Acetobacter nitrogenifigens sp. nov., isolated from
      Kombucha tea.
AB  - The four nitrogen-fixing bacteria so far described in the family Acetobacteraceae
      belong to the genera Gluconacetobacter and Acetobacter. Nitrogen-fixing bacterial
      strain RG1(T) was isolated from Kombucha tea and, based on the phylogenetic
      analysis of 16S rRNA gene sequence which is supported by a high bootstrap value,
      was found to belong to the genus Acetobacter. Strain RG1(T) differed from
      Acetobacter aceti, the nearest member with a 16S rRNA gene sequence similarity of
      98.2 %, and type strains of other Acetobacter species with regard to several
      characteristics of growth features in culture media, growth in nitrogen-free
      medium, production of gamma-pyrone from glucose and dihydroxyacetone from
      glycerol. Strain RG1(T) utilized maltose, glycerol, sorbitol, fructose,
      galactose, arabinose and ethanol, but not methanol as a carbon source. These
      results, along with electrophoretic mobility patterns of nine metabolic enzymes,
      suggest that strain RG1(T) represents a novel nitrogen-fixing species. The
      ubiquinone present was Q-9 and DNA G+C content was 64.1 mol%. Strain RG1(T)
      exhibited a low value of 2-24 % DNA-DNA relatedness to the type strains of
      related acetobacters, which placed it as a separate taxon. On the basis of this
      data, the name Acetobacter nitrogenifigens sp. nov. is proposed, with the type
      strain RG1(T) (=MTCC 6912(T)=LMG 23498(T)).

PMID- 16902030
TI  - Shewanella loihica sp. nov., isolated from iron-rich microbial mats in the
      Pacific Ocean.
AB  - A novel marine bacterial strain, PV-4(T), isolated from a microbial mat located
      at a hydrothermal vent of Loihi Seamount in the Pacific Ocean, has been
      characterized. This micro-organism is orangey in colour, Gram-negative, polarly
      flagellated, facultatively anaerobic and psychrotolerant (temperature range, 0-42
      degrees C). No growth was observed with nitrate, nitrite, DMSO or thiosulfate as
      the electron acceptor and lactate as the electron donor. The major fatty acid
      detected in strain PV-4(T) was iso-C(15 : 0). Strain PV-4(T) had ubiquinones
      consisting mainly of Q-7 and Q-8, and possessed menaquinone MK-7. The DNA G+C
      content of the strain was 53.8 mol% and the genome size was about 4.5 Mbp.
      Phylogenetic analyses based on 16S rRNA gene sequences placed PV-4(T) within the
      genus Shewanella. PV-4(T) exhibited 16S rRNA gene sequence similarity levels of
      99.6 and 97.5 %, respectively, with respect to the type strains of Shewanella
      aquimarina and Shewanella marisflavi. DNA from strain PV-4(T) showed low mean
      levels of relatedness to the DNAs of S. aquimarina (50.5 %) and S. marisflavi
      (8.5 %). On the basis of phylogenetic and phenotypic characteristics, the
      bacterium was classified in the genus Shewanella within a distinct novel species,
      for which the name Shewanella loihica sp. nov. is proposed. The type strain is PV
      4(T) (=ATCC BAA-1088(T)=DSM 17748(T)).

PMID- 16902031
TI  - Myroides pelagicus sp. nov., isolated from seawater in Thailand.
AB  - An aerobic, Gram-negative, non-motile, yellow-to-orange pigmented and rod-shaped
      bacterium, designated strain SM1(T), was isolated from seawater in Thailand and
      subjected to a polyphasic taxonomic study. Phylogenetic analyses based on 16S
      rRNA gene sequences revealed that the novel isolate shared 93-95 % sequence
      similarity with species of the genus Myroides. The DNA-DNA relatedness values of
      strain SM1(T) with Myroides odoratimimus JCM 7460(T) and Myroides odoratus JCM
      7458(T) were below 70 %. The DNA G+C content of strain SM1(T) was 33.6 mol%, the
      major menaquinone was MK-6 and the major fatty acids were C(15 : 0) iso, C(17 :
      1)omega9c iso and C(17 : 0) iso 3-OH. Based on its phenotypic and chemotaxonomic
      characteristics, strain SM1(T) was classified as representing a novel species of
      the genus Myroides, for which the name Myroides pelagicus sp. nov. is proposed.
      The type strain is SM1(T) (=IAM 15337(T)=KCTC 12661(T)).

PMID- 16902032
TI  - Sulfurivirga caldicuralii gen. nov., sp. nov., a novel microaerobic,
      thermophilic, thiosulfate-oxidizing chemolithoautotroph, isolated from a shallow
      marine hydrothermal system occurring in a coral reef, Japan.
AB  - Novel thermophilic bacteria, designated strains VW1 and MM1(T), were isolated
      from hydrothermal fluid and microbial mat samples, respectively, collected from a
      shallow marine hydrothermal system (water depth 22 m) occurring in coral reefs
      off Taketomi Island, Okinawa, Japan. Cells of the two novel strains were motile
      rods with a single polar flagellum in the exponential growth phase. In a medium
      that included elemental sulfur, cells of the two strains became non-motile with
      oval to spherical cell shapes. For both strains, growth occurred at between 30
      and 60 degrees C (optimum temperature of 50-55 degrees C; 60-80 min doubling
      time) and between pH 5.5 and 7.1 (optimum pH 6.0). The isolates were microaerobic
      chemolithoautotrophs capable of using thiosulfate or tetrathionate as the sole
      energy source, O(2) as the sole electron acceptor and CO(2) as the sole carbon
      source. Organic substrates, such as yeast extract and tryptone, inhibited growth
      of both strains. The G+C contents of genomic DNA were 51.3 and 49.5 mol% for
      strains VW1 and MM1(T), respectively. Phylogenetic analysis based on 16S rRNA
      gene sequences indicated that the two strains were closely related to each other
      (99.9 % sequence similarity) and were distantly related to other previously
      described genera within the Gammaproteobacteria. The novel isolates could also be
      differentiated from other gammaproteobacterial genera on the basis of their
      physiological properties. It is suggested that the novel isolates represent the
      type species of a new genus, for which the name Sulfurivirga caldicuralii gen.
      nov., sp. nov. (type strain MM1(T)=JCM 13439(T)=DSM 17737(T)) is proposed.

PMID- 16902033
TI  - Burkholderia silvatlantica sp. nov., a diazotrophic bacterium associated with
      sugar cane and maize.
AB  - In a previous study, nitrogen-fixing isolates were recovered from the rhizosphere
      of maize and from surface-sterilized leaves of sugar cane cultivated in Rio de
      Janeiro, Brazil. On the basis of 16S rRNA gene sequence similarities, these
      isolates were identified as belonging to the genus Burkholderia, and whole-cell
      protein profiles demonstrated that they are closely related to each other. In the
      present study, novel isolates were recovered from the roots of different sugar
      cane varieties cultivated in diverse geographical regions of Brazil. Twenty-one
      nitrogen-fixing isolates were analysed using polyphasic taxonomy criteria,
      including DNA-DNA relatedness, 16S rRNA gene sequence similarities, fatty acid
      profiles, whole-cell-protein patterns and multilocus enzyme electrophoresis
      profiles, as well as morphological, physiological and biochemical
      characterization. The analysis confirmed that these isolates belong to a novel
      species within the genus Burkholderia, for which the name Burkholderia
      silvatlantica sp. nov. is proposed. The type strain, SRMrh-20(T) (=LMG
      23149(T)=ATCC BAA-1244(T)), was isolated from the rhizosphere of maize var.
      Avantis A2345 cultivated in Seropedica, Rio de Janeiro.

PMID- 16902034
TI  - Dyadobacter ginsengisoli sp. nov., isolated from soil of a ginseng field.
AB  - A Gram-negative, aerobic, non-motile, non-spore-forming and rod-shaped bacterium,
      strain Gsoil 043(T), was isolated from soil from a ginseng field in Pocheon
      province, South Korea. The novel isolate was characterized in order to determine
      its taxonomic position. On the basis of 16S rRNA gene sequence similarity, strain
      Gsoil 043(T) was shown to belong to the family 'Flexibacteraceae' and was related
      to Dyadobacter fermentans (96.7 %), Dyadobacter crusticola (96.3 %) and
      Dyadobacter hamtensis (95.8 %). The 16S rRNA gene sequence similarity of the
      novel strain to other recognized species within the family 'Flexibacteraceae' was
      less than 87.0 %. The G+C content of genomic DNA was 48 mol%. Phenotypic and
      chemotaxonomic data (major menaquinone, MK-7; major fatty acids, C(16 :
      1)omega7c, iso-C(15 : 0) and C(16 : 0)) supported the affiliation of strain Gsoil
      043(T) to the genus Dyadobacter. The results of physiological and biochemical
      tests enabled strain Gsoil 043(T) to be differentiated genotypically and
      phenotypically from the three Dyadobacter species with validly published names.
      The novel isolate therefore represents a novel species for which the name
      Dyadobacter ginsengisoli sp. nov. is proposed, with the type strain Gsoil 043(T)
      (=KCTC 12589(T)=LMG 23409(T)).

PMID- 16902035
TI  - Thiorhodococcus mannitoliphagus sp. nov., a purple sulfur bacterium from the
      White Sea.
AB  - A novel purple sulfur bacterium, strain WS(T), was isolated from a microbial mat
      from an estuary of the White Sea. Individual cells are coccoid shaped, motile by
      flagella and do not contain gas vesicles. The mean cell diameter is 1.85 mum
      (range 1.5-2.0 mum). Cell suspensions exhibit a purple-violet colour. They
      contain bacteriochlorophyll a and carotenoids of the rhodopinal series as
      photosynthetic pigments. The novel bacterium is an anoxygenic photoautotroph,
      using sulfide, thiosulfate, sulfite and elemental sulfur as electron donors for
      photosynthesis and is capable of photoassimilating several organic carbon sources
      in the presence of carbonate and a reduced sulfur source (sulfide and/or
      thiosulfate). Sulfur globules, formed during oxidation of sulfide, are stored
      transiently inside the cells. Optimal salinity and pH for growth are at 0.5-2.0 %
      NaCl and pH 7.0-7.5. The DNA base composition of strain WS(T) is 61.8 mol% G+C.
      16S rRNA gene sequence analysis showed that the new isolate belongs to the genus
      Thiorhodococcus, with Thiorhodococcus minor CE2203(T) as the nearest relative
      (sequence similarity of 97.3 %). Several distinct differences from described
      species necessitate the description of a novel species. Thiorhodococcus
      mannitoliphagus sp. nov. is the proposed name, with strain WS(T) (=ATCC BAA
      1228(T)=VKM B-2393(T)) as the type strain.

PMID- 16902036
TI  - Reclassification of Pseudomonas beijerinckii Hof 1935 as Chromohalobacter
      beijerinckii comb. nov., and emended description of the species.
AB  - Pseudomonas beijerinckii (type strain DSM 7218(T)=ATCC 19372(T)=NCIMB 9041(T))
      was isolated from salted beans and was first described by Hof in 1935. 16S rRNA
      gene sequence comparisons demonstrated its close relatedness (>97-99 %) to
      species of the genus Chromohalobacter. A recent isolate from salted herrings
      originating from the Baltic Sea, strain 3b, also clustered phylogenetically
      within this genus. Phenotypic features, substrate utilization, fatty acid
      profile, quinone and polar lipid composition and whole-cell protein patterns
      supported the similarity of strain 3b to P. beijerinckii DSM 7218(T) and
      confirmed its relatedness to members of the genus Chromohalobacter. The G+C
      content of the DNA from strain 3b and P. beijerinckii DSM 7218(T) was 60.4 and
      60.7 mol%, respectively. DNA-DNA hybridization data showed that the two strains
      represent the same species, but are separated from Chromohalobacter canadensis,
      the closest species from a phylogenetic point of view. Therefore, the
      reclassification of Pseudomonas beijerinckii as Chromohalobacter beijerinckii
      comb. nov. (type strain DSM 7218(T)=ATCC 19372(T)=NCIMB 9041(T)) is proposed. The
      species description has been emended considering the new data on both the type
      strain and strain 3b.

PMID- 16902037
TI  - A new genus of the family Micromonosporaceae, Polymorphospora gen. nov., with
      description of Polymorphospora rubra sp. nov.
AB  - Two actinomycete strains were isolated from soil surrounding mangrove roots. The
      isolates formed short spore chains with spores showing diverse shapes. The
      isolates contained glutamic acid, glycine, alanine and meso-diaminopimelic acid
      in the cell wall, 3-O-methylmannose, mannose, galactose and glucose as the whole
      cell sugars and MK-10(H(6)), MK-10(H(4)), MK-9(H(6)) and MK-9(H(4)) as the
      predominant isoprenoid quinones. The isolates formed a distinct taxon in the
      phylogenetic tree of the Micromonosporaceae based on analysis of 16S rRNA gene
      sequences and showed chemical and phenotypic properties that were different from
      members of all of the other genera of this family. Based on these observations,
      it is proposed that the novel isolates belong to a new genus, Polymorphospora
      gen. nov. The type species of the genus is proposed as Polymorphospora rubra sp.
      nov., with strain TT 97-42(T) (=NBRC 101157(T)=DSM 44947(T)) as the type strain.

PMID- 16902038
TI  - Rhodococcus imtechensis sp. nov., a nitrophenol-degrading actinomycete.
AB  - A Gram-positive actinobacterium, strain RKJ300(T), capable of utilizing p
      nitrophenol and 2,4-dinitrophenol, was isolated from a pesticide-contaminated
      site in India. The morphological and chemotaxonomic properties of the isolate
      were typical of members of the genus Rhodococcus. The DNA G+C content was 72
      mol%. Strain RKJ300(T) exhibited the highest level of sequence similarity with
      Rhodococcus wratislaviensis NCIMB 13082(T) (99.3 %), followed by Rhodococcus
      opacus DSM 43205(T) (98.8 %), Rhodococcus percolatus MBS1(T) (98.6 %) and
      Rhodococcus koreensis DNP505(T) (98.1 %). The low levels of DNA-DNA relatedness
      (49-58 %) with the above micro-organisms, and the differences in the biochemical
      and physiological properties, suggest that strain RKJ300(T) should be classified
      within a novel species of the genus Rhodococcus, for which the name Rhodococcus
      imtechensis sp. nov. is proposed. The type strain is RKJ300(T) (=MTCC 7085(T)=JCM
      13270(T)).

PMID- 16902039
TI  - Kocuria himachalensis sp. nov., an actinobacterium isolated from the Indian
      Himalayas.
AB  - A reddish orange bacterium, strain K07-05(T), was isolated from soil during a
      study of the bacterial diversity of a cold desert of the Indian Himalayas and was
      studied by using a polyphasic approach. The organism had morphological and
      chemotaxonomic properties consistent with its classification in the genus
      Kocuria. Phylogenetic analysis of the 16S rRNA gene sequence showed that strain
      K07-05(T) was closely related to Kocuria rosea DSM 20447(T) and Kocuria polaris
      MTCC 3702(T) (98.1 and 97.8 % sequence similarity, respectively), whereas the
      sequence similarity values with respect to the other Kocuria species with validly
      published names were between 96.4 and 94.2 %. However, the genomic relatedness,
      as shown by DNA-DNA hybridization, of strain K07-05(T) and K. polaris MTCC
      3702(T) is 49.5 % and that with K. rosea MTCC 2522(T) is 24.0 %. The DNA G+C
      content of the strain is 75.3 mol%. The above data in combination with the
      phenotypic distinctiveness of K07-05(T) clearly indicate that the strain
      represents a novel species, for which the name Kocuria himachalensis sp. nov. is
      proposed. The type strain is K07-05(T) (=MTCC 7020(T)=DSM 44905(T)=JCM 13326(T)).

PMID- 16902040
TI  - Brooklawnia cerclae gen. nov., sp. nov., a propionate-forming bacterium isolated
      from chlorosolvent-contaminated groundwater.
AB  - Two novel facultatively anaerobic bacterial strains, BL-34(T) and BL-35, isolated
      from groundwater contaminated by a mixture of chlorosolvents were characterized
      using a polyphasic approach. The two strains exhibited essentially identical
      taxonomic features except for a vitamin B(12) requirement by strain BL-35 for
      optimal growth. Phylogenetically, the isolates were affiliated with members of
      the family Propionibacteriaceae and were placed in a phylogenetic branch adjacent
      to, but distinct from, those of the genera Propionimicrobium, Propionibacterium,
      Luteococcus, Propioniferax and Tessaracoccus. The cells of the novel strains were
      Gram-positive, non-motile, non-spore-forming pleomorphic rods. They produced
      catalase but not oxidase, and nitrate reduction did not occur in peptone/yeast
      extract/glucose medium. Propionate and acetate were the predominant products of
      glucose fermentation. Fermentation occurred in the presence of 1,2-dichloroethane
      and 1,1,2-trichloroethane at concentrations up to at least 9.8 mM. The genomic
      DNA G+C content was 67.5-67.9 mol%. Menaquinone MK-9(H(4)) was the predominant
      respiratory quinone and meso-diaminopimelic acid was present in the cell-wall
      peptidoglycan layer. The major cellular fatty acids were C(15 : 0) and anteiso
      C(15 : 0). On the basis of the results obtained in this study, strains BL-34(T)
      and BL-35 should be classified within a novel taxon, for which the name
      Brooklawnia cerclae gen. nov., sp. nov. is proposed. The type strain of
      Brooklawnia cerclae is BL-34(T) (=LMG 23248(T)=NRRL B-41418(T)). An additional
      strain, BL-35 (=LMG 23249=NRRL B-41419), was also characterized.

PMID- 16902041
TI  - Alistipes onderdonkii sp. nov. and Alistipes shahii sp. nov., of human origin.
AB  - Two groups of previously unknown Gram-negative, strictly anaerobic, pigment
      producing, rod-shaped bacteria, which phenotypically and phylogenetically
      displayed a close association with the recently described species Alistipes
      finegoldii, were characterized using phenotypic and molecular taxonomic methods.
      A 16S rRNA gene sequence divergence of approximately 3 % between the two unknown
      bacteria and A. finegoldii, as well as distinguishable biochemical
      characteristics, demonstrates that these organisms are genotypically and
      phenotypically distinct and that each group represents a previously unknown
      subline within the genus Alistipes. Chromosomal DNA-DNA reassociation studies
      further confirmed the separateness of the unidentified bacteria and A.
      finegoldii. On the basis of the phenotypic and phylogenetic findings, two novel
      species, Alistipes onderdonkii sp. nov. and Alistipes shahii sp. nov., are
      proposed. The type strains of A. onderdonkii and A. shahii are WAL 8169(T) (=CCUG
      48946(T)=ATCC BAA-1178(T)) and WAL 8301(T) (=CCUG 48947(T)=ATCC BAA-1179(T)),
      respectively; their DNA G+C contents are 58 and 56 mol%, respectively.

PMID- 16902042
TI  - Hoeflea alexandrii sp. nov., isolated from the toxic dinoflagellate Alexandrium
      minutum AL1V.
AB  - A Gram-negative, aerobic, non-symbiotic bacterium (AM1V30(T)) was isolated from
      the toxic dinoflagellate Alexandrium minutum AL1V. On the basis of 16S rRNA gene
      sequence similarity, strain AM1V30(T) was most closely related (97.4 %
      similarity) to the type strain of Hoeflea marina, which belongs to the family
      Phyllobacteriaceae within the order Rhizobiales of the class Alphaproteobacteria.
      A polyphasic approach was used to clarify the taxonomic position of strain
      AM1V30(T). During the course of this study, a second species was described by
      others as belonging to the genus Hoeflea, namely Hoeflea phototrophica; it showed
      a somewhat higher level of 16S rRNA gene sequence similarity with respect to
      strain AM1V30(T) (98.2 %) and was also taken into account. The fatty acid
      profiles, physiological and biochemical data and DNA G+C content (59.7 mol%)
      support the classification of strain AM1V30(T) as a member of the genus Hoeflea.
      The characteristics of the novel strain were sufficiently distinct to indicate
      that it represents a separate species. To confirm this conclusion, DNA-DNA
      hybridizations were performed: low values (between 15.8 and 29.8 %) were obtained
      in all cases. Thus, AM1V30(T) represents a novel species within the genus
      Hoeflea, for which the name Hoeflea alexandrii sp. nov. is proposed. Strain
      AM1V30(T) (=CECT 5682(T)=DSM 16655(T)) is the type strain.

PMID- 16902043
TI  - Molecular-genetic diversity of the ascomycetous yeast genus Arthroascus:
      Arthroascus babjevae sp. nov., Arthroascus fermentans var. arxii var. nov. and
      geographical populations of Arthroascus schoenii.
AB  - Using molecular and genetic analyses, 28 Arthroascus strains were analysed,
      isolated from widely different geographical localities in Europe, North America,
      Far-East Asia and Hawaii. Most of the strains have been assigned to the species
      Arthroascus schoenii. PCR-RAPD revealed two Japanese Arthroascus strains (UCD 67
      278 and IFO 10138) to have peculiar patterns. Comparative rDNA (D1/D2 26S, ITS1
      and ITS2) sequence analysis showed that the two strains respectively represent a
      novel species and a novel variety. Based on the results of sequence analysis,
      genetic hybridization and DNA-DNA reassociation, two new members of the genus
      Arthroascus are formally described, Arthroascus babjevae sp. nov. (type strain
      UCD 67-278(T)=CBS 9167(T)) and Arthroascus fermentans var. arxii var. nov. (type
      strain IFO 10138(T)=CBS 9168(T)). These results show that A. schoenii has a
      worldwide distribution, while the species Arthroascus javanensis is represented
      only by the type culture CBS 2555(T), isolated in Indonesia. Cluster analysis
      revealed a correlation between PCR-RAPD fingerprints and geographical origin of
      the A. schoenii strains. Despite this molecular differentiation, A. schoenii
      strains collected in different regions of the world formed predominantly fertile
      hybrids, with normal recombination of control markers.

PMID- 16902044
TI  - Lipomyces orientalis sp. nov., a yeast species isolated from soil in Vietnam.
AB  - Five strains of the novel ascogenous yeast species Lipomyces orientalis sp. nov.
      were isolated from soil samples collected in Vietnam. The yeast forms asci
      containing one to four ascospores. The ascospores of L. orientalis have warty
      surfaces and differ from the characteristic striated ascospores of Lipomyces
      tetrasporus. Phylogenetic analyses of D1/D2 26S rDNA and ITS sequences indicate
      that L. orientalis and L. tetrasporus are closely related, but they differ from
      each other by 6 nucleotides in the D1/D2 region and 16 nucleotides in the ITS
      region. The type culture is strain Lip 95(T) (=CBS 10300(T)=NRRL Y-27927(T)).

PMID- 16902045
TI  - Candida floccosa sp. nov., a novel methanol-assimilating yeast species.
AB  - Two methanol-assimilating yeast strains were isolated from a flux of a sessile
      oak (Quercus petrea) in Hungary and one genetically and phenotypically very
      similar strain from a flux of a red oak (Quercus rubra) in Canada. The strains
      exhibited ascomycetous affinity but ascospore formation was not observed. On the
      basis of the sequence of their D1/D2 domain of the large subunit rDNA, as well as
      of their physiological characteristics, they represent a novel yeast species of
      the genus Candida. Therefore Candida floccosa sp. nov. is proposed, with NCAIM
      Y.01581(T) (=CBS 10307(T)=NRRL Y-27951(T)) as the type strain.

PMID- 16902046
TI  - Self-reported pain scores in the emergency department: lack of association with
      vital signs.
AB  - BACKGROUND: Some practitioners and investigators have presumed relationships
      between pain scores and heart rate, blood pressure, or respiratory rate. Previous
      literature has not adequately addressed the association of pain and vital signs.
      OBJECTIVES: To identify any association between self-reported pain and heart
      rate, blood pressure, or respiratory rate. METHODS: In this retrospective,
      observational study, emergency department patients older than 17 years of age
      presenting between May 2004 and April 2005 with verifiable painful diagnoses
      (including nephrolithiasis, myocardial infarction, small bowel obstruction,
      fracture, burn, crush injury, stab wound, amputation, corneal abrasion, and
      dislocation) were identified. Data were extracted from the hospital's database,
      including patients' age, gender, emergency department diagnosis, self-reported
      pain score, heart rate, blood pressure, and respiratory rate. RESULTS: Among
      1,063 subjects, the most common diagnoses were nephrolithiasis (25%; n = 267) and
      fracture (23%; n = 249). The mean (+/- SD) triage pain score was 7 (+/- 3). The
      mean (+/- SD) heart rate was 85 (+/- 16) beats/min, mean (+/- SD) systolic blood
      pressure was 141 (+/- 23) mm Hg, and mean (+/- SD) respiratory rate was 19 (+/-
      3) breaths/min. There were no clinically significant differences in mean vital
      signs across the individual pain scores, as demonstrated by overlapping
      confidence intervals across pain scores. CONCLUSIONS: No clinically significant
      associations were identified between self-reported triage pain scores and heart
      rate, blood pressure, or respiratory rate.

PMID- 16902047
TI  - Are statewide trauma registries comparable? Reaching for a national trauma
      dataset.
AB  - BACKGROUND: Statewide trauma registries have proliferated in the last decade,
      suggesting that information could be aggregated to provide an accurate depiction
      of serious injury in the United States. OBJECTIVES: To determine whether
      variability exists in the composition and content of statewide trauma registries,
      specifically addressing case-acquisition, case-definition (inclusion criteria),
      and registry-coding conventions. METHODS: A cross-sectional, two-part survey was
      administered to managers of all statewide trauma registries. State trauma
      registrars also provided inclusion and exclusion criteria from their state
      registry and abstracted a clinical vignette designed to identify coding
      inconsistencies. RESULTS: Thirty-two states maintain a centralized registry, but
      requirements for data submission vary significantly. Inclusion and exclusion
      criteria also vary, particularly for nontraumatic injuries. Coding conventions
      adopted by states for vague or missing information are dissimilar. When
      abstractions of the clinical vignette are compared, only 19% and 47% of states
      provided similar quantity or content for injury e-coding and diagnostic coding,
      respectively. Injury severity scores (based on diagnostic coding) demonstrated a
      range from 2 to 18. CONCLUSIONS: Statewide trauma registries are prevalent but
      vary significantly in composition and content. Standardizing inclusion criteria,
      variable definitions, and coding conventions would greatly enhance the usability
      of an aggregated, national trauma registry.

PMID- 16902048
TI  - An emergency department-based vaccination program: overcoming the barriers for
      adults at high risk for vaccine-preventable diseases.
AB  - BACKGROUND: More than 10% of the population visit emergency departments (ED)
      every year. Many of these patients are not up-to-date on routine vaccinations
      that could prevent future illnesses. The ED could significantly impact these
      vaccination trends. OBJECTIVES: This study was a feasibility study to determine
      whether patients would be amenable to an ED-based program that provided
      appropriate immunizations when they were at high risk for these diseases. In
      addition, the authors sought to identify barriers that predict high-risk patients
      who did not receive immunizations before ED presentation and to identify barriers
      that predict those high-risk unvaccinated patients who are unwilling to receive
      vaccinations when offered in the ED. METHODS: This study was a prospective cross
      sectional study of all patients arriving in the ED at one inner-city trauma
      center between 10 am and 10 pm over the course of a three-week intervention
      period. The subjects completed a survey that included information about their
      risk of influenza (flu) and pneumococcal disease, their immunization history, and
      their perceptions of their need for immunization. Demographic information
      collected included insurance status, age, gender, and primary language. All high
      risk patients who were not current with their immunizations were offered
      vaccination. The primary outcome was improvement in vaccination coverage based on
      an ED surveillance and treatment system for vaccinations. The secondary outcomes
      were barriers to successful vaccination before ED presentation and barriers to
      acceptance of vaccination in the ED. Results were compared using chi-square test
      and confidence interval analysis. Characteristics of barriers to immunization
      were determined using a logistic regression model. A p-value < 0.05 was
      considered significant. RESULTS: A total of 674 subjects were entered into the
      study. Vaccination of subjects at high risk for flu increased significantly from
      16% before to 83% after ED evaluation and treatment, and vaccination of subjects
      at high risk for pneumococcal disease increased significantly from 18% before to
      84% after ED evaluation and treatment. Significant barriers to vaccination before
      ED presentation were lack of insurance (odds ratio [OR] = 0.31 for flu, 0.22 for
      pneumococcal disease), age younger than 50 years (OR = 0.18 for flu, 0.24 for
      pneumococcal disease), and no perceived need for vaccination (OR = 0.07 for flu).
      The sole significant barrier to vaccine administration in the ED was perceived
      need for vaccination (OR = 0.32 for flu). CONCLUSIONS: An ED-based vaccination
      program is both feasible and successful. Other than a shortage of vaccine, the
      only ED barrier to vaccination (perceived need) might be overcome with patient
      education.

PMID- 16902049
TI  - Emergency department treatment of viral gastritis using intravenous ondansetron
      or dexamethasone in children.
AB  - OBJECTIVES: To compare the efficacy of intravenous ondansetron or dexamethasone
      compared with intravenous fluid therapy alone in children presenting to the
      emergency department with refractory vomiting from viral gastritis who had failed
      attempts at oral hydration. METHODS: This double-blind, randomized, controlled
      trial was performed in a tertiary care pediatric emergency department. Children
      aged 6 months to 12 years presenting with more than three episodes of vomiting in
      the past 24 hours, mild/moderate dehydration, and failed oral hydration were
      included. Patients with other medical causes were excluded. Subjects were
      randomized to dexamethasone 1 mg/kg (15 mg maximum), ondansetron 0.15 mg/kg, or
      placebo (normal saline [NS], 10 mL). All subjects also received intravenous NS at
      10-20 mL/kg/hr. Oral fluid tolerance was evaluated at two and four hours. Those
      not tolerating oral fluids at four hours were admitted. Discharged patients were
      evaluated at 24 and 72 hours for vomiting and repeat health care visits. The
      primary study outcome was hospitalization rates between the groups. Data were
      analyzed using chi-square test, Kruskal-Wallis test, Mantel-Haenszel test, and
      analysis of variance, with p < 0.05 considered significant. RESULTS: A total of
      166 subjects were enrolled; data for analysis were available for 44 NS-treated
      patients, 46 ondansetron-treated patients, and 47 dexamethasone-treated patients.
      Hospital admission occurred in nine patients (20.5%) receiving placebo (NS
      alone), two patients (4.4%) receiving ondansetron, and seven patients (14.9%)
      receiving dexamethasone, with ondansetron significantly different from placebo (p
      = 0.02). Similarly, at two hours, more ondansetron-treated patients (39 [86.6%])
      tolerated oral hydration than NS-treated patients (29 [67.4%]; relative risk,
      1.28; 95% confidence interval = 1.02 to 1.68). There were no differences in
      number of mean episodes of vomiting or repeat visits to health care at 24 and 72
      hours in the ondansetron, dexamethasone, or NS groups. CONCLUSIONS: In children
      with dehydration secondary to vomiting from acute viral gastritis, ondansetron
      with intravenous rehydration improves tolerance of oral fluids after two hours
      and reduces the hospital admission rate when compared with intravenous
      rehydration with or without dexamethasone.

PMID- 16902050
TI  - An independent evaluation of four quantitative emergency department crowding
      scales.
AB  - BACKGROUND: Emergency department (ED) overcrowding has become a frequent topic of
      investigation. Despite a significant body of research, there is no standard
      definition or measurement of ED crowding. Four quantitative scales for ED
      crowding have been proposed in the literature: the Real-time Emergency Analysis
      of Demand Indicators (READI), the Emergency Department Work Index (EDWIN), the
      National Emergency Department Overcrowding Study (NEDOCS) scale, and the
      Emergency Department Crowding Scale (EDCS). These four scales have yet to be
      independently evaluated and compared. OBJECTIVES: The goals of this study were to
      formally compare four existing quantitative ED crowding scales by measuring their
      ability to detect instances of perceived ED crowding and to determine whether any
      of these scales provide a generalizable solution for measuring ED crowding.
      METHODS: Data were collected at two-hour intervals over 135 consecutive sampling
      instances. Physician and nurse agreement was assessed using weighted kappa
      statistics. The crowding scales were compared via correlation statistics and
      their ability to predict perceived instances of ED crowding. Sensitivity,
      specificity, and positive predictive values were calculated at site-specific cut
      points and at the recommended thresholds. RESULTS: All four of the crowding
      scales were significantly correlated, but their predictive abilities varied
      widely. NEDOCS had the highest area under the receiver operating characteristic
      curve (AROC) (0.92), while EDCS had the lowest (0.64). The recommended thresholds
      for the crowding scales were rarely exceeded; therefore, the scales were adjusted
      to site-specific cut points. At a site-specific cut point of 37.19, NEDOCS had
      the highest sensitivity (0.81), specificity (0.87), and positive predictive value
      (0.62). CONCLUSIONS: At the study site, the suggested thresholds of the published
      crowding scales did not agree with providers' perceptions of ED crowding. Even
      after adjusting the scales to site-specific thresholds, a relatively low
      prevalence of ED crowding resulted in unacceptably low positive predictive values
      for each scale. These results indicate that these crowding scales lack
      scalability and do not perform as designed in EDs where crowding is not the norm.
      However, two of the crowding scales, EDWIN and NEDOCS, and one of the READI
      subscales, bed ratio, yielded good predictive power (AROC >0.80) of perceived ED
      crowding, suggesting that they could be used effectively after a period of site
      specific calibration at EDs where crowding is a frequent occurrence.

PMID- 16902051
TI  - Depletion of glutathione induces 4-hydroxynonenal protein adducts and hydroxyurea
      teratogenicity in the organogenesis stage mouse embryo.
AB  - Glutathione (GSH) homeostasis is important during organogenesis. To elucidate the
      impact of GSH depletion in organogenesis stage embryos on oxidative stress and
      drug teratogenicity, l-buthionine-S,R-sulfoximine (BSO) was given to timed
      pregnant CD-1 mice 4 h before exposure to a model teratogen, hydroxyurea (HU)
      [400 mg/kg (HU-400) or 600 mg/kg (HU-600)]. Treatment with BSO or HU alone or
      with BSO plus HU-400 did not alter the ratios of glutathione disulfide/GSH in the
      embryo; in contrast, the combination of BSO plus HU-600 did increase this ratio
      at both 0.5 and 3 h post-HU, indicating the induction of oxidative stress in the
      embryos. Immunoreactivity to a product of lipid peroxidation, 4-hydroxynonenal (4
      HNE) protein adducts, was detected in saline-treated embryos; the intensity and
      nuclear localization of 4-HNE protein adduct immunoreactivity in specific regions
      in the embryo was significantly increased by exposure to BSO alone or BSO and
      either dose of HU. BSO pretreatment increased the spectrum and incidence of
      external and skeletal malformations (curly tail, hind limb malformations,
      hydrocephaly, exencephaly, open eye, spina bifida, and gastroschisis) induced by
      HU-400 and HU-600; BSO exposure did not alter the effects of HU on fetal
      mortality or fetal weights or HU induction of c-Fos heterodimer-dependent
      activator protein 1 DNA binding activity. The formation of 4-HNE protein adducts
      in teratogen-exposed embryos was localized to regions of the embryo that were
      highly susceptible to insult, namely the somites and caudal neural tube,
      correlating the presence of 4-HNE adducts with the disruption of pattern
      formation during organogenesis.

PMID- 16902052
TI  - Transport within the interstitial space, rather than membrane permeability,
      determines norepinephrine recovery in microdialysis.
AB  - Microdialysis is a sampling method that permits measurement of hormones, drugs,
      and other lower molecular weight compounds present in interstitial fluid. We
      developed a straightforward mathematical model that predicts a linear
      relationship between the reciprocal dialysate concentration of the analyte from
      the interstitium and perfusion rate, permitting estimation of the interstitial
      concentration by extrapolation to zero perfusion rate. Conversely, linearity
      between the reciprocal dialysate concentration of internal standard added to the
      perfusion medium (retrodialysis), and the reciprocal perfusion rate, is
      predicted. In nine healthy volunteers, interstitial norepinephrine (NE) was
      estimated by NE measurements in microdialysates obtained from skeletal muscle and
      adipose subcutaneous tissue, using sodium salicylate (Sal) in the perfusion
      buffer as internal standard, at perfusion rates of 2 and 5 mul/min. Comparison
      with microdialysis in vitro by immersing the probe in a large volume of buffer
      containing NE showed that the in vivo (retro)recovery of NE and Sal is almost
      exclusively determined by transport of NE through the interstitial space toward
      and Sal from the membrane and that membrane permeability itself plays a
      negligible role. This was supported by the observation that applying lower body
      negative pressure, a measure that is unlikely to affect membrane permeability,
      resulted in a significant (p < 0.05) decrease of Sal retrorecovery from muscle
      interstitium. This validated new model significantly adds insight into the
      factors determining recovery of substances from the interstitium in microdialysis
      and provides a simpler alternative to previous approaches for estimation of
      interstitial concentrations.

PMID- 16902053
TI  - Photochemical internalization of therapeutic macromolecular agents: a novel
      strategy to kill multidrug-resistant cancer cells.
AB  - Drug resistance is a major problem for chemotherapy. Entrapment of anticancer
      drugs in endolysosomal compartments or active extrusions by plasma membrane
      proteins of the ATP-binding cassette (ABC) superfamily are important resistance
      mechanisms. This study evaluated photochemical internalization (PCI) of membrane
      impermeable macromolecules that are not the target of ABC drug pumps for treating
      multidrug-resistant (MDR) cancer cells. We used the drug-sensitive uterine
      fibrosarcoma cell line MES-SA and its MDR, P-glycoprotein (P-gp)-overexpressing
      derivative MES-SA/Dx5 with the photosensitizer disulfonated meso
      tetraphenylporphine (TPPS(2a)) and broad spectrum illumination. The PCI of
      doxorubicin, the ribosome-inactivating protein gelonin and adenoviral
      transduction were assessed in both cell lines, together with the uptake and
      excretion of TPPS(2a) and of two fluid phase markers easily detectable by
      fluorescence [lucifer yellow (LY) and fluorescein isothiocyanate (FITC)-dextran],
      as a model of gelonin uptake. Both cell lines were resistant to PCI of
      doxorubicin, but equally sensitive to PCI of gelonin, even though the endocytosis
      rates of LY and FITC-dextran were significantly lower in the MDR cells. In
      control studies, MES-SA/Dx5 cells were more resistant to photodynamic therapy
      (TPPS(2a) + light only). This was not mediated by P-gp, as there were no
      differences in the uptake and efflux of TPPS(2a) between the cell lines. After
      adenoviral infection, PCI enhanced gene delivery in both cell lines. In
      conclusion, PCI of macromolecular therapeutic agents that are not targets of P-gp
      is a novel therapeutic strategy to kill MDR cancer cells.

PMID- 16902054
TI  - Effects of glycogen synthase kinase 3beta and cyclin-dependent kinase 5
      inhibitors on morphine-induced analgesia and tolerance in rats.
AB  - Repeated administration of morphine is associated with the development of
      tolerance, yet the mechanism underlying this phenomenon is still poorly
      understood. Recent evidence implicating glycogen synthase kinase 3 (GSK3) in
      opioid receptor signaling pathways has prompted us to investigate its role in
      morphine tolerance. Administration of 10 mg/kg morphine i.p. to Wistar rats twice
      daily for 8 days resulted in complete tolerance to its analgesic effects as
      measured by the tail-flick test. When injections of morphine were preceded by
      intrathecal (i.t.) administration of either an inhibitor of GSK3 [(3-(2,4
      dichlorophenyl)-4-(1-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione (SB216763) or 6
      bromoindirubin-3'oxime] or an inhibitor of cyclin-dependent kinase (Cdk),
      roscovitine, development of tolerance to morphine analgesia was completely
      abolished. In addition, a single i.t. injection of either kinase inhibitor was
      able to restore in a dose-dependent manner the analgesic effect of morphine in
      morphine-tolerant rats. None of the inhibitors in doses used in the present study
      had analgesic effects of their own nor an effect on the analgesic potency of
      morphine. Repeated i.t. administration of either inhibitor had caused an increase
      in abundance of GSK-3beta phosphorylated at Ser(9) in the dorsal lumbar part of
      the spinal cord of rats that were chronically treated with morphine. Furthermore,
      reversal of morphine tolerance by a single injection of either inhibitor was
      always associated with increased abundance of phospho-GSK3beta. In conclusion,
      our data indicate that chronic morphine treatment activates a highly efficient
      pathway by means of which Cdk5 regulates GSK3beta activity.

PMID- 16902055
TI  - Altered creatine dependence of muscle mitochondrial respiration in vitro: what
      are the likely effects in vivo?

PMID- 16902056
TI  - Active venoconstriction is/is not important in maintaining or raising end
      diastolic volume and stroke volume during exercise and orthostasis.

PMID- 16902057
TI  - Cardiac sympathetic afferent stimulation augments the arterial chemoreceptor
      reflex in anesthetized rats.
AB  - Chronic heart failure (CHF) is well known to be associated with both an enhanced
      chemoreceptor reflex and an augmented cardiac "sympathetic afferent reflex"
      (CSAR). The augmentation of the CSAR may play an important role in the enhanced
      chemoreceptor reflex in the CHF state because the same central areas are involved
      in the sympathetic outputs of both reflexes. We determined whether chemical and
      electrical stimulation of the CSAR augments chemoreceptor reflex function in
      normal rats. Under anesthesia, renal sympathetic nerve activity (RSNA) and mean
      arterial pressure (MAP) were recorded. The chemoreceptor reflex was tested by
      unilateral intra-carotid artery bolus injection of potassium cyanide (KCN) and
      nicotine. We found that 1) left ventricular epicardial application of capsaicin
      increased the pressor responses and the RSNA responses to chemoreflex activation
      induced by both KCN and nicotine; 2) when the central end of the left cardiac
      sympathetic nerve was electrically stimulated, both the pressor and the RSNA
      responses to chemoreflex activation induced by KCN were increased; 3)
      pretreatment with intracerebroventricular injection of losartan (500 nmol)
      completely prevented the enhanced chemoreceptor reflex induced by electrical
      stimulation of the cardiac sympathetic nerve; and 4) bilateral microinjection of
      losartan (250 pmol) into the nucleus tractus solitarii (NTS) completely abolished
      the enhanced chemoreceptor reflex by epicardial application of capsaicin. These
      results suggest that both the chemical and electrical stimulation of the CSAR
      augments chemoreceptor reflex and that central ANG II, specially located in the
      NTS, plays a major role in these reflex interactions.

PMID- 16902058
TI  - Lamotrigine and phenytoin, but not amiodarone, impair peripheral chemoreceptor
      responses to hypoxia.
AB  - Amiodarone, lamotrigine, and phenytoin, common antiarrhythmic and antiepileptic
      drugs, inhibit a persistent sodium current in neurons (I(NaP)). Previous results
      from our laboratory suggested that I(NaP) is critical for functionality of
      peripheral chemoreceptors. In this study, we determined the effects of
      therapeutic levels of amiodarone, lamotrigine, and phenytoin on peripheral
      chemoreceptor and ventilatory responses to hypoxia. Action potentials (APs) of
      single chemoreceptor afferents were recorded using suction electrodes advanced
      into the petrosal ganglion of an in vitro rat peripheral chemoreceptor complex.
      AP frequency (at Po(2) approximately 150 Torr and Po(2) approximately 90 Torr),
      conduction time, duration, and amplitude were measured before and during
      perfusion with therapeutic dosages of the drug or vehicle. Hypoxia-induced
      catecholamine secretion within the carotid body was measured using amperometry.
      With the use of whole body plethysmography, respiration was measured in
      unanesthesized rats while breathing room air, 12% O(2), and 5% CO(2), before and
      after intraperitoneal administration of amiodarone, lamotrigine, phenytoin, or
      vehicle. Lamotrigine (10 microM) and phenytoin (5 microM), but not amiodarone (5
      microM), decreased chemoreceptor AP frequency without affecting other AP
      parameters or magnitude of catecholamine secretion. Similarly, lamotrigine (5
      mg/kg) and phenytoin (10 mg/kg) blunted the hypoxic but not the hypercapnic
      ventilatory response. In contrast, amiodarone (2.5 mg/kg) did not alter the
      ventilatory response to hypoxia or hypercapnia. We conclude that lamotrigine and
      phenytoin at therapeutic levels impair peripheral chemoreceptor function and
      ventilatory response to acute hypoxia. These are consistent with I(NaP) serving
      an important function in AP generation and may be clinically important in the
      care of patients using these drugs.

PMID- 16902059
TI  - The effects of short-term hypoxia on motor cortex excitability and neuromuscular
      activation.
AB  - The effects of acute hypoxia on motor cortex excitability, force production, and
      voluntary activation were studied using single- and double-pulse transcranial
      magnetic stimulation techniques in 14 healthy male subjects. Electrical
      supramaximal stimulations of the right ulnar nerve were performed, and
      transcranial magnetic stimulations were delivered to the first dorsal interosseus
      motor cortex area during short-term hypoxic (HX) and normoxic (NX) condition. M
      waves, voluntary activation, F waves, resting motor threshold (rMT), recruitment
      curves (100-140% of rMT), and short-interval intracortical inhibition and
      intracortical facilitation were measured. Moreover, motor-evoked potentials
      (MEPs) and cortical silent periods were determined during brief isometric maximum
      right index finger abductions. Hypoxia was induced by breathing a fraction of
      inspired oxygen of 12% via a face mask. M waves, voluntary activation, and F
      waves did not differ between NX and HX. The rMT was significantly lower in HX
      (55.79 +/- 9.40%) than in NX (57.50 +/- 10.48%) (P < 0.01), whereas MEP
      recruitment curve, short-interval intracortical inhibition, intracortical
      facilitation, maximum right index finger abduction, and MEPs were unaffected by
      HX. In contrast, the cortical silent periods in HX (158.21 +/- 33.96 ms) was
      significantly shortened compared with NX (169.42 +/- 39.69 ms) (P < 0.05). These
      data demonstrate that acute hypoxia results in increased cortical excitability
      and suggest that acute hypoxia alters motor cortical ion-channel function and
      GABAergic transmission.

PMID- 16902060
TI  - Short-term hypoxic exposure at rest and during exercise reduces lung water in
      healthy humans.
AB  - Hypoxia and hypoxic exercise increase pulmonary arterial pressure, cause
      pulmonary capillary recruitment, and may influence the ability of the lungs to
      regulate fluid. To examine the influence of hypoxia, alone and combined with
      exercise, on lung fluid balance, we studied 25 healthy subjects after 17-h
      exposure to 12.5% inspired oxygen (barometric pressure = 732 mmHg) and
      sequentially after exercise to exhaustion on a cycle ergometer with 12.5%
      inspired oxygen. We also studied subjects after a rapid saline infusion (30 ml/kg
      over 15 min) to demonstrate the sensitivity of our techniques to detect changes
      in lung water. Pulmonary capillary blood volume (Vc) and alveolar-capillary
      conductance (D(M)) were determined by measuring the diffusing capacity of the
      lungs for carbon monoxide and nitric oxide. Lung tissue volume and density were
      assessed using computed tomography. Lung water was estimated by subtracting
      measures of Vc from computed tomography lung tissue volume. Pulmonary function
      [forced vital capacity (FVC), forced expiratory volume after 1 s (FEV(1)), and
      forced expiratory flow at 50% of vital capacity (FEF(50))] was also assessed.
      Saline infusion caused an increase in Vc (42%), tissue volume (9%), and lung
      water (11%), and a decrease in D(M) (11%) and pulmonary function (FVC = -12 +/-
      9%, FEV(1) = -17 +/- 10%, FEF(50) = -20 +/- 13%). Hypoxia and hypoxic exercise
      resulted in increases in Vc (43 +/- 19 and 51 +/- 16%), D(M) (7 +/- 4 and 19 +/-
      6%), and pulmonary function (FVC = 9 +/- 6 and 4 +/- 3%, FEV(1) = 5 +/- 2 and 4
      +/- 3%, FEF(50) = 4 +/- 2 and 12 +/- 5%) and decreases in lung density and lung
      water (-84 +/- 24 and -103 +/- 20 ml vs. baseline). These data suggest that 17 h
      of hypoxic exposure at rest or with exercise resulted in a decrease in lung water
      in healthy humans.

PMID- 16902061
TI  - Comparison of hormone responses following light resistance exercise with partial
      vascular occlusion and moderately difficult resistance exercise without
      occlusion.
AB  - Previous studies of contracting muscle with low loading and partial vascular
      occlusion demonstrated hypertrophy and strength adaptations similar to and
      exceeding those observed with traditional moderate to high resistance (Shinohara
      M, Kouzaki M, Yoshihisa T, and Fukunaga T. Eur J Physiol 77: 189-191, 1998;
      Takarada Y, Takazawa H, Sato Y, Takebayashi S, Tanaka Y, and Ishii N. J Appl
      Physiol 88: 2097-2106, 2000; Takarada Y, Sato Y, and Ishii N. Eur J Physiol 86:
      308-314, 2002). The purpose of the study was to determine the anabolic and
      catabolic hormone responses to light resistance exercise combined with partial
      vascular occlusion. Three experimental conditions of light resistance with
      partial occlusion (LRO), moderate resistance with no occlusion (MR), and partial
      occlusion without exercise (OO) were performed by eight healthy subjects [mean 21
      yr (SD 1.8)]. Three sets of single-arm biceps curls and single-leg calf presses
      were completed to failure with 1-min interset rest periods. Workloads of 30 and
      70% one repetition maximum for each exercise were lifted for the LRO and MR
      trials, respectively. Blood samples were taken preexercise, postexercise, and 15
      min postexercise for each experimental condition. Lactate increased significantly
      in the LRO and MR trials and was not significantly different from each other at
      any time point. Growth hormone (GH) increased significantly by fourfold from pre-
      to postexercise in the LRO session but did not change significantly during this
      time period in the MR and OO trials (8.3 +/- 2.3 vs. 2.1 +/- 1.2 and 2.6 +/- 0.94
      microg/l; respectively, P < 0.05). There were no changes in resting total
      testosterone [T; mean 15.7 +/- 1.6 (SE) nmol/l], free testosterone (FT; 54.1 +/-
      4.5 pmol/l), or cortisol (267.6 +/- 22 nmol/l) across all trials and times. In
      conclusion, with similar lactate responses, light exercise combined with partial
      vascular occlusion elicits a greater GH response than moderate exercise without
      occlusion but does not affect T, FT, or cortisol.

PMID- 16902062
TI  - Neurokinin-1 receptor-expressing neurons in the ventral medulla are essential for
      normal central and peripheral chemoreception in the conscious rat.
AB  - Neurokinin-1 receptor immunoreactive (NK1R-ir) neurons and processes are widely
      distributed within the medulla, prominently at central chemoreceptor sites. Focal
      lesions of NK1R-ir neurons in the medullary raphe or the retrotrapezoid nucleus
      partially reduced the CO(2) response in conscious rats. We ask if NK1R-ir cells
      and processes over a wide region of the ventral medulla are essential for central
      and peripheral chemoreception by cisterna magna injection of SSP-SAP, a high
      affinity version of substance P-saporin. After 22 days, NK1R-ir cell loss was 
      79% in the retrotrapezoid nucleus and -65% in the A5 region, which lie close to
      the ventral surface, and -38% in the medullary raphe and -49% in the pre
      Botzinger complex/rostral ventral respiratory group, which lie deeper. Dorsal
      chemoreceptor sites, the caudal nucleus tractus solitarius and the A6 region,
      were unaffected. At 8 and 22 days, these lesions produced 1) hypoventilation
      during air breathing in wakefulness ( approximately 8%) and in non-rapid eye
      movement (NREM) ( approximately 9%) and rapid eye movement ( approximately 14%)
      sleep, as measured over a 4-h period; 2) a substantially reduced ventilatory
      response to 7% CO(2) by 61% in wakefulness and 46-57% in NREM sleep; and 3) a
      decreased ventilatory response to 12% O(2) by 40% in wakefulness and 35% in NREM
      sleep at 8 days, with partial recovery by 22 days. NK1R-ir neurons in the ventral
      medulla are essential for normal central chemoreception, provide a drive to
      breathe, and modulate the peripheral chemoreceptor responses. These effects are
      not state dependent.

PMID- 16902063
TI  - Effect of a short-term diet and exercise intervention on inflammatory/anti
      inflammatory properties of HDL in overweight/obese men with cardiovascular risk
      factors.
AB  - There is significant debate regarding high-density lipoprotein cholesterol (HDL
      C) and high-fiber, low-fat diets. The present study was designed to examine the
      effects of lifestyle modification on the inflammatory/anti-inflammatory
      properties of HDL in obese men (n = 22) with metabolic syndrome factors. Subjects
      were placed on a high-fiber, low-fat diet in a 3-wk residential program where
      food was provided ad libitum and daily aerobic exercise was performed. Fasting
      blood was drawn pre- and postintervention for serum lipids, lipid hydroperoxides,
      and the ability of subject HDL to alter low-density lipoprotein (LDL)-induced
      monocyte chemotactic activity (MCA) in a human artery wall coculture. Induction
      of MCA by control LDL in the absence of HDL was normalized to 1.0. Values >1.0
      after HDL addition indicated proinflammatory HDL; values <1.0 indicated anti
      inflammatory HDL. In addition, proteins involved in regulating HDL function,
      apolipoprotein A-I (apoA-I), paraoxonase 1 and 3, and platelet-activating factor
      acetylhydrolase were measured. After 3 wk, decreases in total-cholesterol, LDL
      cholesterol, HDL-C, triglycerides, total cholesterol-to-HDL cholesterol ratio,
      and lipid hydroperoxides (all P < 0.05) were noted. The HDL inflammatory index
      decreased (P < 0.05) from pro- (1.14 +/- 0.11) to anti-inflammatory (0.94 +/-
      0.09). ApoA-I level and paraoxonase activity did not change; however, platelet
      activating factor acetylhydrolase activity increased (P < 0.05). Despite a
      quantitative reduction in HDL-C, HDL converted from pro- to anti-inflammatory.
      These data indicate that intensive lifestyle modification improves the function
      of HDL even in the face of reduced levels, suggesting increased turnover of
      proinflammatory HDL.

PMID- 16902064
TI  - New perspectives on the mechanical basis for airway hyperreactivity and airway
      hypersensitivity in asthma.
AB  - We revisit the airway wall model of Lambert et. al. (Lambert RK, Wiggs BR, Kuwano
      K, Hogg JC, and Pare PD. J Appl Physiol 74: 2771-2781, 1993). We examine in
      detail the notion of a general airway bistability such that the airway lumen can
      suddenly decrease from a relatively open to a relatively closed condition without
      needing additional increase in active airway smooth muscle (ASM) tension during
      the stimulation. The onset of this bistability is an emergent consequence of the
      balance of forces associated with airway wall properties, parenchymal tissue
      properties, maximum lung elastic recoil, and the maximum stress that the ASM can
      generate. In healthy lungs, we find that all these properties reside in
      conditions that largely prevent the emergence of the bistability even during
      maximum ASM stimulation. In asthmatic airways, however, the airway wall and ASM
      remodeling conditions can tip the balance so as to promote the onset of the
      bistability at a lower dose of ASM stimulation (enhanced sensitivity) and then
      work to amplify the maximum constriction reached by each airway (enhanced
      reactivity). Hence, a larger fraction of asthmatic airways can display overall
      airway hyperreactivity. Simulations studies examine the role of increasing ASM
      maximum tension, airway wall stiffening, reduced lung volume, and decreased
      parenchymal tethering. Results predict that the single most important factor
      causing this airway hyperreactivity is amplified maximum ASM tension and not a
      thickening of the airway wall per se.

PMID- 16902065
TI  - Effects of progressive and maximal exercise on plasma levels of adhesion
      molecules in athletes with sickle cell trait with or without alpha-thalassemia.
AB  - The aim of the study was to examine the effects of exercise on soluble vascular
      cell adhesion molecule-1 (sVCAM-1) and intercellular adhesion molecule-1 (sICAM
      1) in sickle cell trait (SCT) athletes with or without alpha-thalassemia. Six
      athletes with SCT, seven athletes with both SCT and alpha-thalassemia (SCTAT),
      and seven control athletes (Cont) performed an incremental and maximal test on
      cycloergometer. Levels of sICAM-1 and sVCAM-1 were assessed at rest, immediately
      after the end of exercise, and 1, 2, and 24 h after exercise. Although Cont and
      SCTAT groups exhibited similar basal plasma levels of inflammatory and adhesion
      molecules, the SCT group had higher sVCAM-1 basal concentrations. Incremental
      exercise resulted in a significant increase of sVCAM-1 in all subjects, which
      remained elevated only in the SCT group during the recovery period. In
      conclusion, as sVCAM-1 increased with exercise and during the recovery period,
      our findings support the concept that SCT athletes might be at risk for
      microcirculatory disturbances and adhesive phenomena developing at rest and
      several hours after exercise. alpha-Thalassemia might be considered protective
      among exercising SCT subjects.

PMID- 16902066
TI  - Metformin increases the PGC-1alpha protein and oxidative enzyme activities
      possibly via AMPK phosphorylation in skeletal muscle in vivo.
AB  - AMP-activated protein kinase (AMPK), which was activated by an antihyperglycemic
      drug metformin, has been hypothesized to mediate metabolic adaptations. The
      purposes of the present study were 1) to confirm whether acute metformin
      administration induced AMPK phosphorylation and 2) to determine whether chronic
      metformin treatment increased the peroxisome proliferator-activated receptor
      gamma coactivator-1alpha (PGC-1alpha) protein expression, glycolytic and
      oxidative enzyme activities, and cytochrome c and glucose transporter-4 (GLUT4)
      protein expressions in the rat soleus and red and white gastrocnemius muscles.
      The single oral administration of metformin (300 mg/kg body wt) enhanced the AMPK
      phosphorylation at 5 and/or 6 h after treatment. In the chronic study, rats were
      fed either normal chow or chow containing 1% metformin for 14 days. Metformin
      treatment resulted in a mean daily metformin intake of 631 mg.kg body wt(-1).day(
      1). Metformin increased the PGC-1alpha content in all three muscles. Metformin
      increased the hexokinase activity in the white gastrocnemius, the citrate
      synthase activity in all three muscles, and the beta-hydroxyacyl-CoA
      dehydrogenase activity in the soleus. The cytochrome c protein content in the
      soleus muscle also increased. The GLUT4 content was unchanged by metformin. These
      results suggest that metformin enhances the PGC-1alpha expression and
      mitochondrial biogenesis possibly at least in part via AMPK phosphorylation in
      the skeletal muscle. Metformin has thus been proposed to possibly ameliorate
      insulin resistance, at least partially, by means of such metabolic effects.

PMID- 16902067
TI  - Calcium and avian intrapulmonary chemoreceptor response to CO2.
AB  - Intrapulmonary chemoreceptors (IPC) are highly responsive respiratory
      chemoreceptors that innervate the lungs of birds and diapsid reptiles. IPC are
      stimulated by low levels of lung Pco(2), inhibited by high levels of lung Pco(2),
      and their vagal afferents serve as a sensory limb for reflex adjustments of
      breathing depth and rate. Most IPC exhibit both phasic and tonic sensitivity to
      CO(2), and spike frequency adaptation (SFA) contributes to their phasic CO(2)
      responsiveness. To test whether CO(2) responsiveness and SFA in IPC is modulated
      by a Ca(2+)-linked mechanism, we quantified the role of transmembrane Ca(2+)
      fluxes and Ca(2+)-related channels on single-unit IPC function in response to
      phasic changes in inspired Pco(2). We found that 1) broad-spectrum blockade of
      Ca(2+) channels using cadmium or cobalt and blockade of L-type Ca(2+) channels
      using nifedipine increased IPC discharge; 2) activation of L-type Ca(2+) channels
      using BAY K 8644 reduced IPC discharge; 3) blockade of Ca(2+)-activated potassium
      channels using charybdotoxin (antagonist of large-conductance Ca(2+)-dependent
      K(+) channel) increased IPC discharge, but neither charybdotoxin nor apamin
      affected SFA; and 4) blockade of chloride channels, including Ca(2+)-activated
      chloride channels, with niflumic acid decreased IPC discharge at low Pco(2) and
      increased IPC discharge at high Pco(2), resulting in a net attenuation of the IPC
      CO(2) response. We conclude that Ca(2+) influx through L-type Ca(2+) channels has
      an inhibitory effect on IPC afferent discharge and CO(2) sensitivity, that spike
      frequency adaptation is not due to apamin- or charybdotoxin-sensitive Ca(2+)
      activated K(+) channels in IPC, and that chloride channels blocked by niflumic
      acid help modulate IPC CO(2) responses.

PMID- 16902068
TI  - Length and curvature of the dog diaphragm.
AB  - Transdiaphragmatic pressure is a result of both tension in the muscles of the
      diaphragm and curvature of the muscles. As lung volume increases, the pressure
      generating capability of the diaphragm decreases. Whether decrease in curvature
      contributes to the loss in transdiaphragmatic pressure and, if so, under what
      conditions it contributes are unknown. Here we report data on muscle length and
      curvature in the supine dog. Radiopaque markers were attached along muscle
      bundles in the midcostal region of the diaphragm in six beagle dogs of
      approximately 8 kg, and marker locations were obtained from biplanar images at
      functional residual capacity (FRC), during spontaneous inspiratory efforts
      against a closed airway at lung volumes from FRC to total lung capacity, and
      during bilateral maximal phrenic nerve stimulation at the same lung volumes.
      Muscle length and curvature were obtained from these data. During spontaneous
      inspiratory efforts, muscle shortened by 15-40% of length at FRC, but curvature
      remained unchanged. During phrenic nerve stimulation, muscle shortened by 30 to
      nearly 50%, and, for shortening exceeding 52%, curvature appeared to decrease
      sharply. We conclude that diaphragm curvature is nearly constant during
      spontaneous breathing maneuvers in normal animals. However, we speculate that it
      is possible, if lung compliance were increased and the chest wall and the
      diameter of the diaphragm ring of insertion were enlarged, as in the case of
      chronic obstructive pulmonary disease, that decrease in diaphragm curvature could
      contribute to loss of diaphragm function.

PMID- 16902069
TI  - Effects of short-term isocapnic hyperoxia and hypoxia on cardiovascular function.
AB  - Both hypoxia and hyperoxia have major effects on cardiovascular function.
      However, both states affect ventilation and many previous studies have not
      controlled CO(2) tension. We investigated whether hemodynamic effects previously
      attributed to modified O(2) tension were still apparent under isocapnic
      conditions. In eight healthy men, we studied blood pressure (BP), heart rate
      (HR), cardiac index (CI), systemic vascular resistance index (SVRI) and arterial
      stiffness (augmentation index, AI) during 1 h of hyperoxia (mean end-tidal O(2)
      79.6 +/- 2.0%) or hypoxia (pulse oximeter oxygen saturation 82.6 +/- 0.3%).
      Hyperoxia increased SVRI (18.9 +/- 1.9%; P < 0.001) and reduced HR (-10.3 +/-
      1.0%; P < 0.001), CI (-10.3 +/- 1.7%; P < 0.001), and stroke index (SI) (-7.3 +/-
      1.3%; P < 0.001) but had no effect on AI, whereas hypoxia reduced SVRI (-15.2 +/-
      1.2%; P < 0.001) and AI (-10.7 +/- 1.1%; P < 0.001) and increased HR (18.2 +/-
      1.2%; P < 0.001), CI (20.2 +/- 1.8%; P < 0.001), and pulse pressure (13.2 +/-
      2.3%; P = 0.02). The effects of hyperoxia on CI and SVRI, but not the other
      hemodynamic effects, persisted for up to 1 h after restoration of air breathing.
      Although increased oxidative stress has been proposed as a cause of the
      cardiovascular response to altered oxygenation, we found no significant changes
      in venous antioxidant or 8-iso-prostaglandin F(2alpha) levels. We conclude that
      both hyperoxia and hypoxia, when present during isocapnia, cause similar changes
      in cardiovascular function to those described with poikilocapnic conditions.

PMID- 16902070
TI  - Counterpoint: Hypoxic pulmonary vasoconstriction is not mediated by increased
      production of reactive oxygen species.

PMID- 16902073
TI  - Hypoxic pulmonary vasoconstriction is/is not mediated by increased production of
      reactive oxygen species.

PMID- 16902074
TI  - Recreation for children on social assistance, 4-17 years old, pays for itself the
      same year.
AB  - A randomized control trial completed in the Hamilton-Wentworth and Halton regions
      of Ontario, Canada, was created to assess the effects and expense of age
      appropriate provider-initiated and subsidized versus self-directed and self
      financed methods of recreation. Upon completion, this study proved that the
      annual per-person expenditure for the subsidized, quality recreation paid for
      itself by children's lower use of healthcare and social services. The children
      within the subsidized recreation group had lower use of physician, physiotherapy,
      probation, children's aid society, social work, psychologist and services in
      comparison with those in the non-subsidized group. The subsidized group also
      proved to be beneficial for the parents as well. The use of health and social
      services, by the parents in the subsidized group, was also decreased in
      comparison with those of the self-financed group. This group also proved to have
      improvement of the global socioeconomic status, with a 10% greater exit from the
      social assistance program within 1 year.

PMID- 16902075
TI  - Women's knowledge about breast cancer risk and their views of the purpose and
      implications of breast screening--a questionnaire survey.
AB  - OBJECTIVES: To assess women's knowledge and perception of breast screening,
      including its benefits and disadvantages, and explore whether demographic and
      other personal characteristics are associated with accurate knowledge. DESIGN:
      Questionnaire survey of a random sample of 1000 women aged between 49 and 64
      years registered with GPs in Oxfordshire. RESULTS: Thirty-six per cent of women
      knew the lifetime risk of developing breast cancer, and the interpretation of
      numeric risks varied among women. There was an association between inaccurate
      knowledge and lower formal education (P = 0.05). Forty-five per cent of women
      believed that screening prevents breast cancer. Women were of the opinion that
      screening helps early detection, could result in less invasive treatment and
      reassured them. Sixty-three per cent had no concerns about breast screening. The
      main causes of concern were that they would not be invited for further screening
      (exclusively women in their 60s), screening is not offered earlier or more
      frequently, painful mammography and effects of radiation. A minority of women
      were concerned that the pressure exerted on the breasts during mammography may
      itself trigger cancer by displacing and spreading cancer cells. CONCLUSIONS:
      Women's knowledge about breast screening was variable and sometimes incorrect,
      and those with less formal education were more likely to have inaccurate
      knowledge.

PMID- 16902077
TI  - Complementary and alternative medicine in pediatric oncology.
AB  - Children with cancer and their families use complementary and alternative
      medicine (CAM) to reduce symptoms, cope with life-threatening illness, and
      improve overall well-being. Despite numerous published surveys on the use of CAM
      in pediatric oncology, few studies have tested CAM therapies for safety and
      efficacy. A growing body of literature in adult oncology provides evidence for
      the role of CAM to help manage symptoms and reduce distress. Translating this
      research to children requires studies with new models that address family roles
      and include measurement of outcomes relevant to children's developmental stages
      and unique responses. One of the limitations in pediatrics is the small samples
      available to single institutions. Conducting clinical trials through the
      cooperative group mechanism is one way of obtaining sufficient sample sizes to
      determine effectiveness and safety of CAM therapies. This article summarizes
      research to date and describes a beginning approach to measuring outcomes of
      supportive CAM therapies in children with cancer.

PMID- 16902078
TI  - Mind-body therapies for the pediatric oncology patient: matching the right
      therapy with the right patient.
AB  - Pediatric oncology nurses provide care for children across a continuum from the
      point of diagnostic evaluation through treatments and cure or a peaceful,
      dignified death. Nurses provide this care in a wide variety of settings such as
      the home, hospital, clinics, schools, camps, and residential facilities. Mind
      body therapies are being used more frequently in the care of children receiving
      treatment for cancer. Matching the right therapy with the right patient is an
      important component of care.

PMID- 16902079
TI  - Complementary and alternative medicine research and cooperative groups: can it
      happen?
AB  - The use of complementary and alternative medicine (CAM) interventions to
      ameliorate cancer- and treatment-related toxicities is gaining increasing
      attention among clinical investigators. The National Cancer Institute supports a
      number of clinical studies, both descriptive and interventional, of CAM
      interventions across the cancer trajectory, from prevention through diagnosis and
      treatment, survivorship, and end of life. This report highlights the unique
      challenges that clinical investigators face when designing and implementing CAM
      clinical trials through the cooperative groups. This report focuses on 2 CAM
      trials that opened and accrued participants in the Children's Oncology Group. One
      trial is aimed at preventing or reducing mucositis and the other at preventing
      chemotherapy-induced nausea and vomiting.

PMID- 16902080
TI  - Complementary and alternative medicine research initiatives in the Children's
      Oncology Group and the role of the pediatric oncology nurse.
AB  - Complementary and alternative medicine (CAM) has emerged as a new area of
      investigation in cancer research and treatment. CAM modalities are widely used,
      but little is known about their efficacy. The Children's Oncology Group has made
      a major commitment to CAM research in childhood and adolescent cancer, beginning
      with studies of CAM in the area of supportive care. Pediatric oncology nurses, as
      implementing clinicians and collaborating researchers, are critical to the
      success of these studies.

PMID- 16902081
TI  - Future directions of CAM research in pediatric oncology.
AB  - Children with cancer are using complementary and alternative medicine (CAM) to
      relieve symptoms, reduce side effects of treatment, and cope with the emotional
      aspects of having a life-threatening illness. Parental decisions about using CAM
      should be based on studies of efficacy and safety. Unfortunately, little evidence
      of efficacy is available for the majority of CAM therapies. This article
      discusses the methodological challenges to conducting CAM research in children
      and the evidence needed to support integrative medicine in pediatric oncology.

PMID- 16902082
TI  - Factors affecting acceptability to young cancer patients of a psychoeducational
      video game about cancer.
AB  - This study explored whether an action video game about cancer would be acceptable
      to adolescent and young adult cancer patients as a tool for learning about cancer
      and self-care during treatment. Interviews about a proposed video game were
      conducted with 43 young cancer patients, who also completed questionnaires
      measuring personality and adaptive style. Data were analyzed to assess the
      overall acceptability of the proposed video game and to reveal any factors
      associated with measures of acceptability. Most participants expressed
      willingness to play the game and a moderate degree of interest in it. Cancer
      content in the game was not a deterrent for most participants. Game acceptability
      was not affected by personality variables or adaptive style. It is concluded that
      an action video game using cancer themes could be useful to nurses as a tool to
      improve understanding and self care of adolescent and young adult cancer
      patients.

PMID- 16902083
TI  - Children receiving chemotherapy at home: perceptions of children and parents.
AB  - The aim of this descriptive exploratory study was to determine the perspectives
      of parents and children with cancer on a home chemotherapy program. Qualitative
      analyses were used to organize data from 24 parents and 14 children into emerging
      themes. Themes included (1) financial and time costs, (2) disruption to daily
      routines, (3) psychological and physical effects, (4) recommendations and
      caveats, and (5) preference for home chemotherapy. When home chemotherapy was
      compared with hospital clinic-based chemotherapy, parents reported fewer
      financial and time costs and less disruption to their work and family schedules,
      and children reported more time to play/study, improved school attendance, and
      engagement in normal activities. Although some parents felt more secure with
      hospital chemotherapy, most found it more exhausting and stressful. At home,
      children selected places for their treatment and some experienced fewer side
      effects. Although some coordination/communication problems existed, the majority
      of parents and children preferred home chemo-therapy. Home chemotherapy treatment
      is a viable, acceptable, and positive health care delivery alternative from the
      perspective of parents and children with cancer.

PMID- 16902084
TI  - An initial map of insertion and deletion (INDEL) variation in the human genome.
AB  - Although many studies have been conducted to identify single nucleotide
      polymorphisms (SNPs) in humans, few studies have been conducted to identify
      alternative forms of natural genetic variation, such as insertion and deletion
      (INDEL) polymorphisms. In this report, we describe an initial map of human INDEL
      variation that contains 415,436 unique INDEL polymorphisms. These INDELs were
      identified with a computational approach using DNA re-sequencing traces that
      originally were generated for SNP discovery projects. They range from 1 bp to
      9989 bp in length and are split almost equally between insertions and deletions,
      relative to the chimpanzee genome sequence. Five major classes of INDELs were
      identified, including (1) insertions and deletions of single-base pairs, (2)
      monomeric base pair expansions, (3) multi-base pair expansions of 2-15 bp repeat
      units, (4) transposon insertions, and (5) INDELs containing random DNA sequences.
      Our INDELs are distributed throughout the human genome with an average density of
      one INDEL per 7.2 kb of DNA. Variation hotspots were identified with up to 48
      fold regional increases in INDEL and/or SNP variation compared with the
      chromosomal averages for the same chromosomes. Over 148,000 INDELs (35.7%) were
      identified within known genes, and 5542 of these INDELs were located in the
      promoters and exons of genes, where gene function would be expected to be
      influenced the greatest. All INDELs in this study have been deposited into dbSNP
      and have been integrated into maps of human genetic variation that are available
      to the research community.

PMID- 16902085
TI  - Identification of potential regulatory motifs in odorant receptor genes by
      analysis of promoter sequences.
AB  - Mouse odorant receptors (ORs) are encoded by >1000 genes dispersed throughout the
      genome. Each olfactory neuron expresses one single OR gene, while the rest of the
      genes remain silent. The mechanisms underlying OR gene expression are poorly
      understood. Here, we investigated if OR genes share common cis-regulatory
      sequences in their promoter regions. We carried out a comprehensive analysis in
      which the upstream regions of a large number of OR genes were compared. First,
      using RLM-RACE, we generated cDNAs containing the complete 5'-untranslated
      regions (5'-UTRs) for a total number of 198 mouse OR genes. Then, we aligned
      these cDNA sequences to the mouse genome so that the 5' structure and
      transcription start sites (TSSs) of the OR genes could be precisely determined.
      Sequences upstream of the TSSs were retrieved and browsed for common elements. We
      found DNA sequence motifs that are overrepresented in the promoter regions of the
      OR genes. Most motifs resemble O/E-like sites and are preferentially localized
      within 200 bp upstream of the TSSs. Finally, we show that these motifs
      specifically interact with proteins extracted from nuclei prepared from the
      olfactory epithelium, but not from brain or liver. Our results show that the OR
      genes share common promoter elements. The present strategy should provide
      information on the role played by cis-regulatory sequences in OR gene regulation.

PMID- 16902088
TI  - Hoxa2- and rhombomere-dependent development of the mouse facial somatosensory
      map.
AB  - In the mouse trigeminal pathway, sensory inputs from distinct facial structures,
      such as whiskers or lower jaw and lip, are topographically mapped onto the
      somatosensory cortex through relay stations in the thalamus and hindbrain. In the
      developing hindbrain, the mechanisms generating such maps remain elusive. We
      found that in the principal sensory nucleus, the whisker-related map is
      contributed by rhombomere 3-derived neurons, whereas the rhombomere 2-derived
      progeny supply the lower jaw and lip representation. Moreover, early Hoxa2
      expression in neuroepithelium prevents the trigeminal nerve from ectopically
      projecting to the cerebellum, whereas late expression in the principal sensory
      nucleus promotes selective arborization of whisker-related afferents and
      topographic connectivity to the thalamus. Hoxa2 inactivation further results in
      the absence of whisker-related maps in the postnatal brain. Thus, Hoxa2- and
      rhombomere 3-dependent cues determine the whisker area map and are required for
      the assembly of the whisker-to-barrel somatosensory circuit.

PMID- 16902086
TI  - Common inheritance of chromosome Ia associated with clonal expansion of
      Toxoplasma gondii.
AB  - Toxoplasma gondii is a globally distributed protozoan parasite that can infect
      virtually all warm-blooded animals and humans. Despite the existence of a sexual
      phase in the life cycle, T. gondii has an unusual population structure dominated
      by three clonal lineages that predominate in North America and Europe, (Types I,
      II, and III). These lineages were founded by common ancestors approximately10,000
      yr ago. The recent origin and widespread distribution of the clonal lineages is
      attributed to the circumvention of the sexual cycle by a new mode of transmission
      asexual transmission between intermediate hosts. Asexual transmission appears to
      be multigenic and although the specific genes mediating this trait are unknown,
      it is predicted that all members of the clonal lineages should share the same
      alleles. Genetic mapping studies suggested that chromosome Ia was unusually
      monomorphic compared with the rest of the genome. To investigate this further, we
      sequenced chromosome Ia and chromosome Ib in the Type I strain, RH, and the Type
      II strain, ME49. Comparative genome analyses of the two chromosomal sequences
      revealed that the same copy of chromosome Ia was inherited in each lineage,
      whereas chromosome Ib maintained the same high frequency of between-strain
      polymorphism as the rest of the genome. Sampling of chromosome Ia sequence in
      seven additional representative strains from the three clonal lineages supports a
      monomorphic inheritance, which is unique within the genome. Taken together, our
      observations implicate a specific combination of alleles on chromosome Ia in the
      recent origin and widespread success of the clonal lineages of T. gondii.

PMID- 16902087
TI  - Uneven chromosome contraction and expansion in the maize genome.
AB  - Maize (Zea mays or corn), both a major food source and an important cytogenetic
      model, evolved from a tetraploid that arose about 4.8 million years ago (Mya). As
      a result, maize has extensive duplicated regions within its genome. We have
      sequenced the two copies of one such region, generating 7.8 Mb of sequence
      spanning 17.4 cM of the short arm of chromosome 1 and 6.6 Mb (25.6 cM) from the
      long arm of chromosome 9. Rice, which did not undergo a similar whole genome
      duplication event, has only one orthologous region (4.9 Mb) on the short arm of
      chromosome 3, and can be used as reference for the maize homoeologous regions.
      Alignment of the three regions allowed identification of syntenic blocks, and
      indicated that the maize regions have undergone differential contraction in genic
      and intergenic regions and expansion by the insertion of retrotransposable
      elements. Approximately 9% of the predicted genes in each duplicated region are
      completely missing in the rice genome, and almost 20% have moved to other genomic
      locations. Predicted genes within these regions tend to be larger in maize than
      in rice, primarily because of the presence of predicted genes in maize with
      larger introns. Interestingly, the general gene methylation patterns in the maize
      homoeologous regions do not appear to have changed with contraction or expansion
      of their chromosomes. In addition, no differences in methylation of single genes
      and tandemly repeated gene copies have been detected. These results, therefore,
      provide new insights into the diploidization of polyploid species.

PMID- 16902089
TI  - Satellite gravity measurements confirm accelerated melting of Greenland ice
      sheet.
AB  - Using time-variable gravity measurements from the Gravity Recovery and Climate
      Experiment (GRACE) satellite mission, we estimate ice mass changes over Greenland
      during the period April 2002 to November 2005. After correcting for the effects
      of spatial filtering and limited resolution of GRACE data, the estimated total
      ice melting rate over Greenland is -239 +/- 23 cubic kilometers per year, mostly
      from East Greenland. This estimate agrees remarkably well with a recent
      assessment of -224 +/- 41 cubic kilometers per year, based on satellite radar
      interferometry data. GRACE estimates in southeast Greenland suggest accelerated
      melting since the summer of 2004, consistent with the latest remote sensing
      measurements.

PMID- 16902090
TI  - Imaging intracellular fluorescent proteins at nanometer resolution.
AB  - We introduce a method for optically imaging intracellular proteins at nanometer
      spatial resolution. Numerous sparse subsets of photoactivatable fluorescent
      protein molecules were activated, localized (to approximately 2 to 25
      nanometers), and then bleached. The aggregate position information from all
      subsets was then assembled into a superresolution image. We used this method-
      termed photoactivated localization microscopy--to image specific target proteins
      in thin sections of lysosomes and mitochondria; in fixed whole cells, we imaged
      vinculin at focal adhesions, actin within a lamellipodium, and the distribution
      of the retroviral protein Gag at the plasma membrane.

PMID- 16902092
TI  - Back to the people.

PMID- 16902093
TI  - Geophysics. Stealth tsunami surprises Indonesian coastal residents.

PMID- 16902091
TI  - Opposing activities protect against age-onset proteotoxicity.
AB  - Aberrant protein aggregation is a common feature of late-onset neurodegenerative
      diseases, including Alzheimer's disease, which is associated with the misassembly
      of the Abeta(1-42) peptide. Aggregation-mediated Abeta(1-42) toxicity was reduced
      in Caenorhabditis elegans when aging was slowed by decreased insulin/insulin
      growth factor-1-like signaling (IIS). The downstream transcription factors, heat
      shock factor 1, and DAF-16 regulate opposing disaggregation and aggregation
      activities to promote cellular survival in response to constitutive toxic protein
      aggregation. Because the IIS pathway is central to the regulation of longevity
      and youthfulness in worms, flies, and mammals, these results suggest a
      mechanistic link between the aging process and aggregation-mediated
      proteotoxicity.

PMID- 16902094
TI  - France. Cancer chief calls it quits after controversy.

PMID- 16902095
TI  - Science education. Evolution trumps intelligent design in Kansas vote.

PMID- 16902096
TI  - Imaging. Brilliant X-rays reveal fruits of a brilliant mind.

PMID- 16902097
TI  - Evolution. Native mussel quickly evolves fear of invasive crab.

PMID- 16902098
TI  - Genomics. Biofuels to be focus of new DOE centers.

PMID- 16902099
TI  - Nuclear reprocessing. DOE outlines two roads to recycling spent fuel.

PMID- 16902100
TI  - Infectious diseases. Gastrointestinal virus strikes European cruise ships.

PMID- 16902101
TI  - Molecular imaging. New optics strategies cut through diffraction barrier.

PMID- 16902102
TI  - Career development. NSF wants PIs to mentor their postdocs.

PMID- 16902103
TI  - Astronomy. Do gamma ray bursts always line up with galaxies?

PMID- 16902104
TI  - Theoretical physics. A 'landscape' too far?

PMID- 16902105
TI  - Theoretical physics. A reluctant convert.

PMID- 16902106
TI  - Jim Hanken profile. Shaking the dust off Agassiz's museum.

PMID- 16902107
TI  - Jim Hanken profile. An outsider moves in.

PMID- 16902108
TI  - Astronomy. Low road to the heavens.

PMID- 16902109
TI  - The ethics of influenza vaccination.

PMID- 16902110
TI  - Complex choices better made unconsciously?

PMID- 16902111
TI  - Comment on "Gene regulatory networks and the evolution of animal body plans".
AB  - Davidson and Erwin (Reviews, 10 February 2006, p. 796) argued that known
      microevolutionary processes cannot explain the evolution of large differences in
      development that characterize phyla. Instead, they proposed that phyla arise from
      novel evolutionary processes involving large mutations acting on conserved core
      pathways of development. I question some of their assumptions and show that
      natural selection adequately explains the origin of new phyla.

PMID- 16902112
TI  - Science communication. Public acceptance of evolution.

PMID- 16902113
TI  - Immunology. When F-actin becomes too much of a good thing.

PMID- 16902114
TI  - Geophysics. Toward "supervolcano" technology.

PMID- 16902115
TI  - Computer science. Creating a science of the Web.

PMID- 16902116
TI  - Astronomy. Testing star formation theory.

PMID- 16902117
TI  - Microbiology. Breaking the barrier between commensalism and pathogenicity.

PMID- 16902118
TI  - Botany. Plant cells CLEave their way to differentiation.

PMID- 16902120
TI  - Migration and dispersal. As the seas warm.

PMID- 16902121
TI  - Migration and Dispersal. Sound sightings.

PMID- 16902122
TI  - Migration and Dispersal. Inching toward movement ecology.

PMID- 16902123
TI  - Migration and Dispersal. Tag team.

PMID- 16902124
TI  - Migration and Dispersal. Arduous journeys.

PMID- 16902125
TI  - Migration and Dispersal. Follow the footprints.

PMID- 16902126
TI  - Long-distance dispersal of plants.
AB  - Long-distance dispersal (LDD) of plants poses challenges to research because it
      involves rare events driven by complex and highly stochastic processes. The
      current surge of renewed interest in LDD, motivated by growing recognition of its
      critical importance for natural populations and communities and for humanity,
      promises an improved, quantitatively derived understanding of LDD. To gain deep
      insights into the patterns, mechanisms, causes, and consequences of LDD, we must
      look beyond the standard dispersal vectors and the mean trend of the distribution
      of dispersal distances. "Nonstandard" mechanisms such as extreme climatic events
      and generalized LDD vectors seem to hold the greatest explanatory power for the
      drastic deviations from the mean trend, deviations that make the nearly
      impossible LDD a reality.

PMID- 16902127
TI  - From individual dispersal to species ranges: perspectives for a changing world.
AB  - Dispersal is often risky to the individual, yet the long-term survival of
      populations depends on having a sufficient number of individuals that move, find
      each other, and locate suitable breeding habitats. This tension has consequences
      that rarely meet our conservation or management goals. This is particularly true
      in changing environments, which makes the study of dispersal urgently topical in
      a world plagued with habitat loss, climate change, and species introductions.
      Despite the difficulty of tracking mobile individuals over potentially vast
      ranges, recent research has revealed a multitude of ways in which dispersal
      evolution can either constrain, or accelerate, species' responses to
      environmental changes.

PMID- 16902128
TI  - Conflicting evidence about long-distance animal navigation.
AB  - Because of conflicting evidence about several fundamental issues, long-distance
      animal navigation has yet to be satisfactorily explained. Among the unsolved
      problems are the nature of genetic spatial control of migration and the
      relationships between celestial and magnetic compass mechanisms and between
      different map-related cues in orientation and homing, respectively. In addition,
      navigation is expected to differ between animal groups depending on sensory
      capabilities and ecological conditions. Evaluations based on modern long-term
      tracking techniques of the geometry of migration routes and individual migration
      history, combined with behavioral experiments and exploration of the sensory and
      genetic mechanisms, will be crucial for understanding the spatial principles that
      guide animals on their global journeys.

PMID- 16902129
TI  - How and why do insects migrate?
AB  - Countless numbers of insects migrate within and between continents every year,
      and yet we know very little about the ultimate reasons and proximate mechanisms
      that would explain these mass movements. Here we suggest that perhaps the most
      important reason for insects to migrate is to hedge their reproductive bets. By
      spreading their breeding efforts in space and time, insects distribute their
      offspring over a range of environmental conditions. We show how the study of
      individual long-distance movements of insects may contribute to a better
      understanding of migration. In the future, advances in tracking methods may
      enable the global surveillance of large insects such as desert locusts.

PMID- 16902130
TI  - Going east: new genetic and archaeological perspectives on the modern human
      colonization of Eurasia.
AB  - The pattern of dispersal of biologically and behaviorally modern human
      populations from their African origins to the rest of the occupied world between
      approximately 60,000 and 40,000 years ago is at present a topic of lively debate,
      centering principally on the issue of single versus multiple dispersals. Here I
      argue that the archaeological and genetic evidence points to a single successful
      dispersal event, which took genetically and culturally modern populations fairly
      rapidly across southern and southeastern Asia into Australasia, and with only a
      secondary and later dispersal into Europe.

PMID- 16902131
TI  - Single-molecule, motion-based DNA sequencing using RNA polymerase.
AB  - We present a method for sequencing DNA that relies on the motion of single RNA
      polymerase molecules. When a given nucleotide species limits the rate of
      transcription, polymerase molecules pause at positions corresponding to the rare
      base. An ultrastable optical trapping apparatus capable of base pair resolution
      was used to monitor transcription under limiting amounts of each of the four
      nucleotide species. From the aligned patterns of pauses recorded from as few as
      four molecules, we determined the DNA sequence. This proof of principle
      demonstrates that the motion of a processive nucleic acid enzyme may be used to
      extract sequence information directly from DNA.

PMID- 16902132
TI  - Magnetic fields in the formation of sun-like stars.
AB  - We report high-angular-resolution measurements of polarized dust emission toward
      the low-mass protostellar system NGC 1333 IRAS 4A. We show that in this system
      the observed magnetic field morphology is in agreement with the standard
      theoretical models of the formation of Sun-like stars in magnetized molecular
      clouds at scales of a few hundred astronomical units; gravity has overcome
      magnetic support, and the magnetic field traces a clear hourglass shape. The
      magnetic field is substantially more important than turbulence in the evolution
      of the system, and the initial misalignment of the magnetic and spin axes may
      have been important in the formation of the binary system.

PMID- 16902133
TI  - Time-resolved seismic tomography detects magma intrusions at Mount Etna.
AB  - The continuous volcanic and seismic activity at Mount Etna makes this volcano an
      important laboratory for seismological and geophysical studies. We used repeated
      three-dimensional tomography to detect variations in elastic parameters during
      different volcanic cycles, before and during the October 2002-January 2003 flank
      eruption. Well-defined anomalous low P- to S-wave velocity ratio volumes were
      revealed. Absent during the pre-eruptive period, the anomalies trace the
      intrusion of volatile-rich (>/=4 weight percent) basaltic magma, most of which
      rose up only a few months before the onset of eruption. The observed time changes
      of velocity anomalies suggest that four-dimensional tomography provides a basis
      for more efficient volcano monitoring and short- and midterm eruption forecasting
      of explosive activity.

PMID- 16902134
TI  - An experimental study of the coloring problem on human subject networks.
AB  - Theoretical work suggests that structural properties of naturally occurring
      networks are important in shaping behavior and dynamics. However, the
      relationships between structure and behavior are difficult to establish through
      empirical studies, because the networks in such studies are typically fixed. We
      studied networks of human subjects attempting to solve the graph or network
      coloring problem, which models settings in which it is desirable to distinguish
      one's behavior from that of one's network neighbors. Networks generated by
      preferential attachment made solving the coloring problem more difficult than did
      networks based on cyclical structures, and "small worlds" networks were easier
      still. We also showed that providing more information can have opposite effects
      on performance, depending on network structure.

PMID- 16902135
TI  - Insignificant change in Antarctic snowfall since the International Geophysical
      Year.
AB  - Antarctic snowfall exhibits substantial variability over a range of time scales,
      with consequent impacts on global sea level and the mass balance of the ice
      sheets. To assess how snowfall has affected the thickness of the ice sheets in
      Antarctica and to provide an extended perspective, we derived a 50-year time
      series of snowfall accumulation over the continent by combining model simulations
      and observations primarily from ice cores. There has been no statistically
      significant change in snowfall since the 1950s, indicating that Antarctic
      precipitation is not mitigating global sea level rise as expected, despite recent
      winter warming of the overlying atmosphere.

PMID- 16902136
TI  - Divergent induced responses to an invasive predator in marine mussel populations.
AB  - Invasive species may precipitate evolutionary change in invaded communities. In
      southern New England (USA) the invasive Asian shore crab, Hemigrapsus sanguineus,
      preys on mussels (Mytlius edulis), but the crab has not yet invaded northern New
      England. We show that southern New England mussels express inducible shell
      thickening when exposed to waterborne cues from Hemigrapsus, whereas naive
      northern mussel populations do not respond. Yet, both populations thicken their
      shells in response to a long-established crab, Carcinus maenas. Our findings are
      consistent with the rapid evolution of an inducible morphological response to
      Hemigrapsus within 15 years of its introduction.

PMID- 16902137
TI  - Loss of a harvested fish species disrupts carbon flow in a diverse tropical
      river.
AB  - Harvesting threatens many vertebrate species, yet few whole-system manipulations
      have been conducted to predict the consequences of vertebrate losses on ecosystem
      function. Here, we show that a harvested migratory detrital-feeding fish
      (Prochilodontidae: Prochilodus mariae) modulates carbon flow and ecosystem
      metabolism. Natural declines in and experimental removal of Prochilodus decreased
      downstream transport of organic carbon and increased primary production and
      respiration. Thus, besides its economic value, Prochilodus is a critical
      ecological component of South American rivers. Lack of functional redundancy for
      this species highlights the importance of individual species and, contrary to
      theory, suggests that losing one species from lower trophic levels can affect
      ecosystem functioning even in species-rich ecosystems.

PMID- 16902138
TI  - Polarized light cues underlie compass calibration in migratory songbirds.
AB  - Migratory songbirds use the geomagnetic field, stars, the Sun, and polarized
      light patterns to determine their migratory direction. To prevent navigational
      errors, it is necessary to calibrate all of these compass systems to a common
      reference. We show that migratory Savannah sparrows use polarized light cues from
      the region of sky near the horizon to recalibrate the magnetic compass at both
      sunrise and sunset. We suggest that skylight polarization patterns are used to
      derive an absolute (i.e., geographic) directional system that provides the
      primary calibration reference for all of the compasses of migratory songbirds.

PMID- 16902139
TI  - Requirement for coronin 1 in T lymphocyte trafficking and cellular homeostasis.
AB  - The evolutionarily conserved actin-related protein (Arp2/3) complex is a key
      component of actin filament networks that is dynamically regulated by nucleation
      promoting and inhibitory factors. Although much is known about actin assembly,
      the physiologic functions of inhibitory proteins are unclear. We generated
      coronin 1-/- mice and found that coronin 1 exerted an inhibitory effect on
      cellular steady-state F-actin formation via an Arp2/3-dependent mechanism.
      Whereas coronin 1 was required for chemokine-mediated migration, it was
      dispensable for T cell antigen receptor functions in T cells. Moreover, actin
      dynamics, through a mitochondrial pathway, was linked to lymphocyte homeostasis.

PMID- 16902140
TI  - Dodeca-CLE peptides as suppressors of plant stem cell differentiation.
AB  - In plants and animals, small peptide ligands that signal in cell-cell
      communication have been suggested to be a crucial component of development. A
      bioassay of single-cell transdifferentation demonstrates that a dodecapeptide
      with two hydroxyproline residues is the functional product of genes from the CLE
      family, which includes CLAVATA3 in Arabidopsis. The dodecapeptide suppresses
      xylem cell development at a concentration of 10(-11) M and promotes cell
      division. An application, corresponding to all 26 Arabidopsis CLE protein family
      members, of synthetic dodecapeptides reveals two counteracting signaling pathways
      involved in stem cell fate.

PMID- 16902141
TI  - A plant peptide encoded by CLV3 identified by in situ MALDI-TOF MS analysis.
AB  - The Arabidopsis CLAVATA3 (CLV3) gene encodes a stem cell-specific protein
      presumed to be a precursor of a secreted peptide hormone. Matrix-assisted laser
      desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS) applied to
      in situ Arabidopsis tissues determined the structure of a modified 12-amino acid
      peptide (MCLV3), which was derived from a conserved motif in the CLV3 sequence.
      Synthetic MCLV3 induced shoot and root meristem consumption as cells
      differentiated into other organs, displaying the typical phenotype of transgenic
      plants overexpressing CLV3. These results suggest that the functional peptide of
      CLV3 is MCLV3.

PMID- 16902142
TI  - Escherichia coli induces DNA double-strand breaks in eukaryotic cells.
AB  - Transient infection of eukaryotic cells with commensal and extraintestinal
      pathogenic Escherichia coli of phylogenetic group B2 blocks mitosis and induces
      megalocytosis. This trait is linked to a widely spread genomic island that
      encodes giant modular nonribosomal peptide and polyketide synthases. Contact with
      E. coli expressing this gene cluster causes DNA double-strand breaks and
      activation of the DNA damage checkpoint pathway, leading to cell cycle arrest and
      eventually to cell death. Discovery of hybrid peptide-polyketide genotoxins in E.
      coli will change our view on pathogenesis and commensalism and open new
      biotechnological applications.

PMID- 16902143
TI  - Tequila, a neurotrypsin ortholog, regulates long-term memory formation in
      Drosophila.
AB  - Mutations in the human neurotrypsin gene are associated with autosomal recessive
      mental retardation. To further understand the pathophysiological consequences of
      the lack of this serine protease, we studied Tequila (Teq), the Drosophila
      neurotrypsin ortholog, using associative memory as a behavioral readout. We found
      that teq inactivation resulted in a long-term memory (LTM)-specific defect. After
      LTM conditioning of wild-type flies, teq expression transiently increased in the
      mushroom bodies. Moreover, specific inhibition of teq expression in adult
      mushroom bodies resulted in a reversible LTM defect. Hence, the Teq pathway is
      essential for information processing in Drosophila.

PMID- 16902145
TI  - Polymorphisms in human homeobox HLX1 and DNA repair RAD51 genes increase the risk
      of therapy-related acute myeloid leukemia.
AB  - Studies of radiation-induced acute myeloid leukemia (AML) in mice suggest that
      the number of target stem cells is a risk factor, and the HLX1 homeobox gene,
      which is important for hematopoietic development, is a candidate gene. The
      distribution of the C/T-3' untranslated region (UTR) polymorphism in HLX1 in
      patients with AML and therapy-related AML (t-AML) compared with controls was
      therefore determined. The presence of the variant HLX1 allele significantly
      increases the risk of t-AML (OR = 3.36, 95% CI, 1.65-6.84). The DNA repair gene
      RAD51 (135G/C-5' UTR) polymorphism also increases t-AML risk, and when combined
      analysis was performed on both RAD51 and HLX1 variant alleles, a synergistic 9.5
      fold increase (95% CI, 2.22-40.64) in the risk of t-AML was observed. We suggest
      that the HLX1 polymorphism has an effect on stem cell numbers, whereas an
      increased DNA repair capacity (RAD51) will suppress apoptosis, a genetic
      interaction that may increase the number of genomes at risk during cancer
      therapy.

PMID- 16902144
TI  - Cytotoxic T cells generated against heteroclitic peptides kill primary tumor
      cells independent of the binding affinity of the native tumor antigen peptide.
AB  - Heteroclitic peptide modifications increase immunogenicity, allowing generation
      of cytotoxic T lymphocytes (CTLs) against weakly immunogenic tumor-associated
      antigens (TAAs). A critical issue is whether T cells generated against
      heteroclitic peptides retain the ability to recognize and kill tumor cells
      expressing the original weak TAAs, and whether there is a lower threshold of
      binding affinity of the native peptides, below which such CTLs can still kill
      primary tumor cells. To examine this we used a model examining the ability of
      native and heteroclitic immunoglobulin (Ig)-derived peptides to generate CTLs
      that can kill chronic lymphocytic leukemia (CLL) cells. We demonstrate that CTLs
      generated against heteroclitic peptides have enhanced killing of CD40-activated B
      cells pulsed with either heteroclitic (P < .001) or native peptide (P = .04) and
      primary CLL cells (P = .01). The novel finding reported here is that the rate
      limiting factor appears to be the ability to generate CTLs and that once
      generated, CTL lysis of primary tumor cells is independent of the binding
      affinity of the native peptide. These findings have implications for vaccination
      strategies in malignancies and are currently being further examined in vivo in
      murine models.

PMID- 16902146
TI  - The immunosuppressive drug FK778 induces regulatory activity in stimulated human
      CD4+ CD25- T cells.
AB  - The induction of transplantation tolerance involves a T-cell-mediated process of
      immune regulation. In clinical transplantation, the use of immunosuppressive
      drugs that promote or facilitate this process would be highly desirable. Here, we
      investigated the tolerance-promoting potential of the immunosuppressive drug
      FK778, currently under development for clinical therapy. Using a human allogeneic
      in vitro model we showed that, upon T-cell receptor (TCR) triggering, FK778
      induced a regulatory phenotype in CD4+ CD25- T cells. Purified CD4+ CD25- T cells
      primed in the presence of FK778 showed hyporesponsiveness upon restimulation with
      alloantigen in the absence of the drug. This anergic state was reversible by
      exogenous interleukin-2 (IL-2) and was induced independent of naturally occurring
      CD4+ CD25+ regulatory T cells. Pyrimidine restriction was a crucial requirement
      for the de novo induction of regulatory activity by FK778. The FK778-induced
      anergic cells showed suppressor activity in a cell-cell contact-dependent manner;
      were CD25(high), CD45RO+, CD27-, and CD62L-; and expressed cytotoxic T-lymphocyte
      associated antigen-4 (CTLA-4), glucocorticoid-induced tumor necrosis factor
      receptor (GITR), and FoxP3. The cells revealed delayed p27(kip1) degradation and
      enhanced phosphorylation of STAT3. In conclusion, the new drug FK778 shows
      tolerizing potential through the induction of a regulatory T-cell subset in CD4+
      CD25- T cells.

PMID- 16902147
TI  - HIV-1-driven regulatory T-cell accumulation in lymphoid tissues is associated
      with disease progression in HIV/AIDS.
AB  - Regulatory T (Treg) cells accumulate in the lymphoid tissues of human
      immunodeficiency virus (HIV)-infected individuals, contributing to the inability
      of the immune system to control virus replication. We investigate here Treg-cell
      numbers and functional markers (FOXP3, CTLA-4, IDO, and TGF-beta1) in lymphoid
      tissues from untreated infected hosts with progressive or nonprogressive disease
      (HIV-infected humans and simian immunodeficiency virus [SIV]-infected macaques).
      We found that increased numbers of FOXP3(+) T cells as well as increased
      expression of Treg-cell-associated functional markers were detected only during
      progressive disease. Such increases were not correlated with immune activation.
      Of importance, a high-perforin/FOXP3 ratio was associated with nonprogressive
      disease, suggesting that the immune control of virus replication represents a
      balance between cell-mediated immune responses and Treg-cell-mediated counter
      regulation of such responses. Furthermore, using an in vitro model of Treg-cell
      HIV interactions, we showed that exposure of Treg cells to HIV selectively
      promoted their survival via a CD4-gp120-dependent pathway, thus providing an
      underlying mechanism for the accumulation of Treg cells in infected hosts with
      active viral replication. Considered together, our findings imply that
      therapeutic manipulation of Treg-cell number and/or function could improve immune
      control of HIV infection.

PMID- 16902148
TI  - Immunologic and functional evidence for anti-Siglec-9 autoantibodies in
      intravenous immunoglobulin preparations.
AB  - Human intravenous immunoglobulin (IVIg) preparations are increasingly used for
      the treatment of autoimmune diseases. Earlier work demonstrated the presence of
      autoantibodies against Fas in IVIg, suggesting that IVIg might be able to induce
      caspase-dependent cell death in Fas-sensitive cells. In this study, we
      demonstrate that sialic acid-binding Ig-like lectin 9 (Siglec) represents a
      surface molecule on neutrophils that is activated by IVIg, resulting in caspase
      dependent and caspase-independent forms of cell death. Neutrophil death was
      mediated by naturally occurring anti-Siglec-9 autoantibodies present in IVIg.
      Moreover, the efficacy of IVIg-mediated neutrophil killing was enhanced by the
      proinflammatory cytokines granulocyte/macrophage colony-stimulating factor (GM
      CSF) and interferon-gamma (IFN-gamma), and this additional cell death required
      reactive oxygen species (ROSs) but not caspases. Anti- Siglec-9 autoantibody
      depleted IVIg failed to induce this caspase-independent neutrophil death. These
      findings contribute to our understanding of how IVIg preparations exert their
      immunoregulatory effects under pathologic conditions and may provide a possible
      explanation for the neutropenia that is sometimes seen in association with IVIg
      therapy.

PMID- 16902150
TI  - Coordinated acquisition of inhibitory and activating receptors and functional
      properties by developing human natural killer cells.
AB  - The stages of human natural killer (NK) cell differentiation are not well
      established. Culturing CD34(+) progenitors with interleukin 7 (IL-7), IL-15, stem
      cell factor (SCF), FLT-3L, and murine fetal liver cell line (EL08.1D2), we
      identified 2 nonoverlapping subsets of differentiating CD56(+) cells based on
      CD117 and CD94 (CD117(high)CD94(-) and CD117(low/-)CD94(+) cells). Both
      populations expressed CD161 and NKp44, but differed with respect to NKp30, NKp46,
      NKG2A, NKG2C, NKG2D, CD8, CD16, and KIR. Only the CD117(low/-) CD94(+) population
      displayed cytotoxicity and interferon-gamma production. Both populations arose
      from a single CD34(+)CD38(-) Lin(-) cell and their percentages changed over time
      in a reciprocal fashion, with CD117(high)CD94(-) cells predominating early and
      decreasing due to an increase of the CD117(low/-)CD94(+) population. These 2
      subsets represent distinct stages of NKcell differentiation, since purified
      CD117(high) CD94(-) cells give rise to CD117(low/-)CD94(+) cells. The stromal
      cell line (EL08.1D2) facilitated the transition from CD117(high)CD94(-) to
      CD117(low/-)CD94(+) via an intermediate phenotype (CD117(low)CD94(low/-)).
      EL08.1D2 also maintained the mature phenotype, preventing the reversion of
      CD117(low/-)CD94(+) cells to the intermediate (CD117(low)CD94(low/-)) phenotype.
      An analogous population of CD56(+)CD117(high)CD94(-) cells was found in cord
      blood. The identified stages of NK-cell differentiation provide evidence for
      coordinated acquisition of HLA-specific inhibitory receptors (ie, CD94/NKG2A) and
      function in developing human NK cells.

PMID- 16902151
TI  - Prognostic significance of Epstein-Barr virus in nodal peripheral T-cell
      lymphoma, unspecified: A Groupe d'Etude des Lymphomes de l'Adulte (GELA) study.
AB  - Peripheral T-cell lymphomas (PTCLs) are rare and have a dismal prognosis. The
      most frequent subtype is PTCL, unspecified. Epstein-Barr virus (EBV) has been
      detected in around 40% of cases, but its prognostic significance is not fully
      established. Lymph node samples from 110 patients with PTCL, unspecified included
      in LNH87 and LNH93 trials were available. EBV status was studied by EBV-encoded
      small RNA in situ hybridization (EBER-ISH). EBER-ISH showed positive cells in 45
      (41%) of 110 patients. Pretreatment characteristics were comparable between
      positive and negative cases, except for male sex (80% versus 60%, respectively, P
      = .02). Only 50% of patients achieved complete remission with a 5-year event-free
      survival (EFS) and overall survival (OS) of 21% and 30%, respectively. EBER-ISH
      positivity was the sole factor linked with worse EFS, with a 5-year probability
      of 11% for positive patients. In univariate analysis, factors affecting OS were
      EBER-ISH positivity, high LDH level, and age older than 60 years. In multivariate
      analysis, EBER-ISH was associated with a worse OS in the elderly population. Time
      dependent analysis showed that the negative impact of EBV was essentially seen in
      the first 2 years following diagnosis. These results warrant further studies
      regarding pathogenesis and specific treatment approaches for EBV-associated PTCL
      patients.

PMID- 16902152
TI  - The tryptophan catabolite L-kynurenine inhibits the surface expression of NKp46-
      and NKG2D-activating receptors and regulates NK-cell function.
AB  - Tryptophan (Trp) catabolism mediated by indoleamine 2,3-dioxygenase (IDO) plays a
      central role in the regulation of T-cell-mediated immune responses. In this
      study, we also demonstrate that natural killer (NK)-cell function can be
      influenced by IDO. Indeed, l-kynurenine, a Trp-derived catabolite resulting from
      IDO activity, was found to prevent the cytokine-mediated up-regulation of the
      expression and function of specific triggering receptors responsible for the
      induction of NK-cell-mediated killing. The effect of l-kynurenine appears to be
      restricted to NKp46 and NKG2D, while it does not affect other surface receptors
      such as NKp30 or CD16. As a consequence, l-kynurenine-treated NK cells display
      impaired ability to kill target cells recognized via NKp46 and NKG2D. Instead,
      they maintain the ability to kill targets, such as dendritic cells (DCs), that
      are mainly recognized via the NKp30 receptor. The effect of l-kynurenine, which
      is effective at both the transcriptional and the protein level, can be reverted,
      since NK cells were found to recover their functional competence after washing.

PMID- 16902153
TI  - Phase 1 clinical results with tandutinib (MLN518), a novel FLT3 antagonist, in
      patients with acute myelogenous leukemia or high-risk myelodysplastic syndrome:
      safety, pharmacokinetics, and pharmacodynamics.
AB  - Tandutinib (MLN518/CT53518) is a novel quinazoline-based inhibitor of the type
      III receptor tyrosine kinases: FMS-like tyrosine kinase 3 (FLT3), platelet
      derived growth factor receptor (PDGFR), and KIT. Because of the correlation
      between FLT3 internal tandem duplication (ITD) mutations and poor prognosis in
      acute myelogenous leukemia (AML), we conducted a phase 1 trial of tandutinib in
      40 patients with either AML or high-risk myelodysplastic syndrome (MDS).
      Tandutinib was given orally in doses ranging from 50 mg to 700 mg twice daily The
      principal dose-limiting toxicity (DLT) of tandutinib was reversible generalized
      muscular weakness, fatigue, or both, occurring at doses of 525 mg and 700 mg
      twice daily. Tandutinib's pharmacokinetics were characterized by slow
      elimination, with achievement of steady-state plasma concentrations requiring
      greater than 1 week of dosing. Western blotting showed that tandutinib inhibited
      phosphorylation of FLT3 in circulating leukemic blasts. Eight patients had FLT3
      ITD mutations; 5 of these were evaluable for assessment of tandutinib's
      antileukemic effect. Two of the 5 patients, treated at 525 mg and 700 mg twice
      daily, showed evidence of antileukemic activity, with decreases in both
      peripheral and bone marrow blasts. Tandutinib at the MTD (525 mg twice daily)
      should be evaluated more extensively in patients with AML with FLT3-ITD mutations
      to better define its antileukemic activity.

PMID- 16902154
TI  - siRNA silencing of calumenin enhances functional factor IX production.
AB  - To improve production of functional fully gamma-carboxylated recombinant human
      clotting factor IX (r-hFIX), cell lines stably overexpressing r-hFIX have been
      engineered to also overexpress proteins of the gamma-carboxylation system. Here
      we demonstrate that siRNA silencing of calumenin, an inhibitor of the gamma
      carboxylation system, enhances production of functional r-hFIX produced by
      engineered BHK21 cells. The production yield of functional r-hFIX was 80% in
      engineered cells where calumenin had been silenced 78%. We propose that this high
      yield expression system can easily be adapted to overproduce functional forms of
      all members of the vitamin K-dependent protein family.

PMID- 16902156
TI  - Cis and trans regulation of hepcidin expression by upstream stimulatory factor.
AB  - Hepcidin is the presumed negative regulator of systemic iron levels; its
      expression is induced in iron overload, infection, and inflammation, and by
      cytokines, but is suppressed in hypoxia and anemia. Although the gene is
      exquisitely sensitive to changes in iron status in vivo, its mRNA is devoid of
      prototypical iron-response elements, and it is therefore not obvious how it may
      be regulated by iron flux. The multiplicity of effectors of its expression also
      suggests that the transcriptional circuitry controlling the gene may be very
      complex indeed. In delineating enhancer elements within both the human and mouse
      hepcidin gene promoters, we show here that members of the basic helix-loop-helix
      leucine zipper (bHLH-ZIP) family of transcriptional regulators control hepcidin
      expression. The upstream stimulatory factor 2 (USF2), previously linked to
      hepcidin through gene ablation in inbred mice, appears to exert a polar or cis
      acting effect, while USF1 may act in trans to control hepcidin expression. In
      mice, we found variation in expression of both hepcidin genes, driven by these
      transcription factors. In addition, c-Myc and Max synergize to control the
      expression of this hormone, supporting previous findings for the role of this
      couple in regulating iron metabolism. Transcriptional activation by both
      USF1/USF2 and c-Myc/Max heterodimers occurs through E-boxes within the promoter.
      Site-directed mutagenesis of these elements rendered the promoter unresponsive to
      USF1/USF2 or c-Myc/Max. Dominant-negative mutants of USF1 and USF2 reciprocally
      attenuated promoter transactivation by both wild-type USF1 and USF2. Promoter
      occupancy by the transcription factors was confirmed by DNA-binding and chromatin
      immunoprecipitation assays. Taken together, it would appear that synergy between
      these members of the bHLH-ZIP family of transcriptional regulators may subserve
      an important role in iron metabolism as well as other pathways in which hepcidin
      may be involved.

PMID- 16902155
TI  - Growth factor receptors as regulators of hematopoiesis.
AB  - Nearly 15 years have elapsed since the US Food and Drug Administration last
      approved a major new hematopoietic cytokine. Promiscuous binding to multiple
      receptors, or to receptors expressed by multiple tissues, reduces growth factor
      specificity and promotes side effects. Here we show that hematopoiesis can be
      differentially regulated using receptors rather than ligands. Conditional
      derivatives of both fibroblast growth factor receptor-1 (F36VFGFR1) and the
      thrombopoietin receptor (F36VMpl) induced a sustained expansion of mouse marrow
      cells ex vivo, and erythroid cells in vivo. Only F36VFGFR1 could support the ex
      vivo expansion of short-term repopulating hematopoietic stem cells (HSCs), the ex
      vivo survival of long-term repopulating HSCs, and the prolonged in vivo expansion
      of granulocytes, monocytes, and platelets. Only F36VMpl induced a response
      sufficiently rapid to accelerate recovery from radiation-induced anemia. These
      results establish receptors as a new class of hematopoietic regulators possessing
      activities unobtainable with growth factors.

PMID- 16902157
TI  - Induction of monocytic tissue factor expression after rewarming from hypothermia
      in vivo is counteracted by heat shock in c-Jun-dependent manner.
AB  - OBJECTIVE: Triggering of tissue factor (TF)-mediated blood coagulation leads to
      the development of disseminated intravascular coagulation during rewarming from
      hypothermia. We studied post-rewarming TF levels, activity, and surface
      redistribution, along with the regulation of TF gene transcription in mononuclear
      cells (MNCs) obtained from an in vivo rat model. METHODS AND RESULTS: Rewarming
      after a 5-hour episode of 15 degrees C hypothermia caused an increase in TF
      activity, protein levels, and externalization of TF antigen in rat MNCs. This was
      accompanied by a dramatic elevation of c-Jun and JNK phosphorylation, and the
      absence of EGR-1 and NF-kappaB activation. To search for a stimulus to counteract
      c-Jun-mediated induction of TF activity in MNCs from rewarmed rats, we applied
      heat shock pretreatment one day before the hypothermia/rewarming experiment. This
      restored post-rewarming TF activity, protein levels, and surface-to-total TF
      ratio in rat MNCs to normothermic levels. Furthermore, in heat shock-pretreated
      animals, rewarming failed to increase phosphorylated c-Jun and JNK levels. We
      attribute this to the profound overexpression of heat shock protein 70 and
      inhibition of JNK. CONCLUSIONS: MNCs respond to rewarming from hypothermia by an
      induction of active TF antigen. This effect is dependent on c-Jun activation and
      is abolished by heat shock pretreatment.

PMID- 16902158
TI  - In vivo characterization and quantification of atherosclerotic carotid plaque
      components with multidetector computed tomography and histopathological
      correlation.
AB  - OBJECTIVE: In a previous in vitro study we have demonstrated that atherosclerotic
      plaque components can be characterized with multidetector computed tomography
      (MDCT) based on differences in Hounsfield values (HV). Now we evaluated the use
      of MDCT in vivo to characterize and quantify atherosclerotic carotid plaque
      components compared with histology as reference standard. METHODS AND RESULTS:
      Fifteen symptomatic patients with carotid stenosis (>70%) underwent MDCT
      angiography before carotid endarterectomy (CEA). From each CEA specimen 3
      histological sections and corresponding MDCT images were selected. The HV of the
      major plaque components were assessed. The measured HV were: 657+/-416HU, 88+/
      18HU, and 25+/-19HU for calcifications, fibrous tissue, and lipid core,
      respectively. The cut-off value to differentiate lipid core from fibrous tissue
      and fibrous tissue from calcifications was based on these measurements and set at
      60 HU and 130 HU, respectively. Regression plots showed good correlations
      (R2>0.73) between MDCT and histology except for lipid core areas, which had a
      good correlation (R2=0.77) only in mildly calcified (0% to 10%) plaques.
      CONCLUSIONS: MDCT is able to quantify total plaque area, calcifications, and
      fibrous tissue in atherosclerotic carotid plaques in good correlation with
      histology. Lipid core can only be adequately quantified in mildly calcified
      plaques.

PMID- 16902159
TI  - Serum levels of mannose-binding lectin and the risk of future coronary artery
      disease in apparently healthy men and women.
AB  - OBJECTIVE: To determine the association between serum levels of mannose-binding
      lectin (MBL) and the risk of future coronary artery disease (CAD) in apparently
      healthy men and women. METHODS AND RESULTS: We performed a prospective case
      control study among apparently healthy men and women nested in the EPIC-Norfolk
      cohort. Baseline concentrations of MBL were measured in serum samples of 946
      patients who experienced a myocardial infarction or died of CAD during follow-up,
      and 1799 matched controls who remained free of CAD. Among men, median MBL levels
      were 1.63 ng/mL (interquartile range [IQR]: 0.59 to 3.80) in cases and 1.20 ng/mL
      (IQR: 0.48 to 3.37) in controls. Among women, median MBL levels were 1.02 ng/mL
      (IQR: 0.43 to 2.95) in cases and 1.01 ng/mL (IQR: 0.43 to 2.94) in controls.
      After adjustment, the odds ratio in men for future CAD was 1.59 (95% confidence
      interval [CI]: 1.09 to 2.32; P for linearity=0.01) for those in the highest
      quartile compared with those in the lowest quartile. In women no such relation
      was observed. CONCLUSIONS: Elevated levels of MBL are associated with an
      increased risk of future CAD in apparently healthy men but not in women. The sex
      difference merits further exploration.

PMID- 16902160
TI  - Individual measurement and significance of carotid intima, media, and intima
      media thickness by B-mode ultrasonographic image processing.
AB  - OBJECTIVE: We assessed the clinical significance of intima (IT), media (MT), and
      intima-media (IMT) thickness of the common carotid artery using B-mode
      ultrasonographic image processing. METHODS AND RESULTS: One hundred seventy
      consecutive patients underwent common carotid artery scanning using high
      resolution ultrasonography. A total of 150 patients could be analyzed off-line
      using ultrasonographic image processing, devised for individual measurement of
      IT, MT, and IMT. By univariate analysis, IT (range, 0.27 to 0.41 mm) was
      associated with age, whereas MT (range, 0.27 to 0.74 mm) and IMT (range, 0.49 to
      1.12 mm) were associated with age, fibrinogen, and creatinine. Among
      atherosclerosis risk factors, hypertension was associated with thickness of all 3
      layers, whereas smoking was associated with IT only. By multivariate analysis, IT
      was associated with age, hypertension, and smoking, whereas MT and IMT were
      associated with age, hypertension, and blood urea nitrogen level. CONCLUSIONS:
      Carotid IT is associated with smoking, whereas age and hypertension are
      associated with thickness of all 3 arterial layers. Our results suggest a
      differential response of the vasculature to systemic risk factors.

PMID- 16902161
TI  - Lipoprotein-associated phospholipase A2 and prognosis after myocardial infarction
      in the community.
AB  - OBJECTIVE: We evaluated the role of lipoprotein-associated phospholipase A2 (Lp
      PLA2), an inflammatory biomarker, in defining risk after myocardial infarction
      (MI). METHODS AND RESULTS: Olmsted County, Minn, residents who experienced an MI
      meeting standardized criteria between 2003 and 2005 (n = 271) were prospectively
      identified and followed. Lp-PLA2 levels were measured at baseline and evaluated
      along with traditional risk indicators. Lp-PLA2 was modestly associated with
      total and low-density lipoprotein cholesterol, smoking, and age (inversely) but
      not with MI characteristics or severity, comorbidities, C-reactive protein, or
      the time from symptom onset to blood sampling. During the first year of follow
      up, 42 deaths occurred. The survival estimates (95% confidence intervals [CI]) at
      1 year were 92% (86% to 98%), 85% (78% to 93%), and 74% (65% to 84%) in the
      lowest, middle, and upper Lp-PLA2 tertiles, respectively (P = 0.007). After
      adjustment for age and sex, the hazard ratios for death in the middle and upper
      Lp-PLA2 tertiles were 2.20 (95% CI: 0.88 to 5.54) and 4.93 (95% CI: 2.10 to
      11.60), compared with the lowest tertile, respectively (P(trend) < 0.001).
      Further adjustment for other risk indicators resulted in even stronger
      associations. Lp-PLA2 also contributed to risk discrimination as indicated by the
      increases in the area under the receiver operating characteristic curves obtained
      in each of the models examined (all P < or = 0.05). CONCLUSIONS: Among community
      subjects presenting with MI, increased Lp-PLA2 levels measured early after MI are
      strongly and independently associated with mortality and provide incremental
      value in risk discrimination over traditional predictors.

PMID- 16902162
TI  - Hepatocyte growth factor regulates E box-dependent plasminogen activator
      inhibitor type 1 gene expression in HepG2 liver cells.
AB  - OBJECTIVE: We sought to determine the etiologic mechanism of pleiotropic growth
      factor, hepatocyte growth factor (HGF), as a regulator of hepatic synthesis of
      plasminogen activator inhibitor (PAI)-1, the physiological inhibitor of
      fibrinolysis and a potential inducer of atherothrombosis. METHODS AND RESULTS:
      HGF increased PAI-1 mRNA expression and PAI-1 protein accumulation in the
      conditioned media of human liver-derived HepG2 cells, and increased hepatic PAI-1
      mRNA expression in vivo in mice. HGF-inducible PAI-1 mRNA was attenuated by
      U0126, a specific inhibitor of mitogen-activated protein kinase (MAPK) kinase,
      and genistein, an inhibitor of tyrosine kinase. HGF increased the human PAI-1
      promoter (-829 to +36 bp) activity, and deletion and mutation analysis uncovered
      a functional E box (5'-CACATG-3') at positions -158 to -153 bp. Electrophoretic
      mobility shift assays demonstrated that this E box binds upstream stimulatory
      factors (USFs). HGF phosphorylated USFs through MAPK and tyrosine kinase
      pathways. Co-transfection of USF1 expression vector increased PAI-1 promoter
      activity. Sterol regulatory element-binding protein-1 attenuated HGF-inducible
      PAI-1 promoter activity. CONCLUSIONS: Because USFs are involved in the regulation
      of carbohydrates and lipid metabolism, HGF-mediated PAI-1 production may provide
      a novel link between atherothrombosis and metabolic derangements. Targeting HGF
      signaling pathway may modulate the thrombotic risk in high-risk patients.

PMID- 16902163
TI  - High-molecular-weight kininogen fragments stimulate the secretion of cytokines
      and chemokines through uPAR, Mac-1, and gC1qR in monocytes.
AB  - OBJECTIVE: Plasma high-molecular-weight kininogen (HK) is cleaved in inflammatory
      diseases by kallikrein to HKa with release of bradykinin (BK). We postulated a
      direct link between HKa and cytokine/chemokine release. METHODS AND RESULTS: HKa,
      but not BK, releases cytokines tumor necrosis factor (TNF)-alpha, interleukin
      (IL)-1beta, IL-6, and chemokines IL-8 and MCP-1 from isolated human mononuclear
      cells. At a concentration of 600 nM, glutathione-S-transferase (GST) fusion
      proteins of kininogen domain 3 (D3), a fragment of domain 3, E7P (aaG255-Q292),
      HK domain 5 (D5), the D5 recombinant peptides HG (aa K420-D474) and HGK (aa H475
      S626) stimulated secretion of IL-1beta from mononuclear cells. Monoclonal
      antibodies (MAbs) specific for D5 or specific for D3 blocked release of IL-1beta
      by HKa, supporting the importance of both domains. Antibodies to HK receptors on
      leukocytes including Mac-1, LFA-1, uPAR, and C1qR inhibited IL-1beta secretion
      induced by tKa 98%, 89%, 85%, and 62%, respectively. Fractionation of mononuclear
      cells identified the responsible cell, a blood monocyte. Inhibitors of signaling
      pathways NFkB, JNK, and p38 but not extracellular signal-regulated kinase (ERK)
      decreased cytokine release from mononuclear cells. HKa increased the synthesis of
      IL-1beta as deduced by an increase of IL-1beta mRNA at 1 to 2 hours. CONCLUSIONS:
      HKa domains 3 and 5 may contribute to the pathogenesis of inflammatory diseases
      by releasing IL-1beta from human monocytes using intracellular signaling pathways
      initiated by uPAR, beta2 integrins and gC1qR.

PMID- 16902164
TI  - Sca-1+ progenitors derived from embryonic stem cells differentiate into
      endothelial cells capable of vascular repair after arterial injury.
AB  - BACKGROUND: Embryonic stem cells possess the ability to differentiate into
      endothelium. The ability to produce large volumes of endothelium from embryonic
      stem cells could provide a potential therapeutic modality for vascular injury. We
      describe an approach that selects endothelial cells using magnetic beads that may
      be used therapeutically to treat arterial injury. METHODS AND RESULTS: Large
      numbers of endothelial cells (ECs) with high purity were produced using Sca-1+
      cells isolated with magnetic beads from predifferentiated embryonic stem cells
      (ESCs) cultured in alpha-MEM containing 10 ng/mL VEGF165 for a minimum of 21 days
      (esEC). The transcription regulator histone deacetylase (HDAC3) was essential for
      VEGF-induced EC differentiation. Immunofluorescence or fluorescence-activated
      cell sorter (FACS) analysis revealed that esECs expressed a full range of EC
      lineage-specific markers including CD31, CD106, CD144, Flk-1, Flt-1, and von
      Willebrand factor (vWF). FACS analysis confirmed that 99% of esECs were CD31
      positive and 75% vWF-positive. Furthermore, almost all cells were positive for
      DiI-acLDL uptake. When matrigel containing esECs was subcutaneously implanted
      into mice, various vessel-like structures were observed indicating their
      endothelial cell like phenotype. In keeping with this, when esECs infected with
      adenovirus-LacZ were injected into denuded femoral arteries of mice, they were
      found to form a neo-endothelium that covered the injured areas (86%+/-13.6%),
      which resulted in a 73% decrease in neointimal area 2 weeks after injury.
      CONCLUSIONS: We conclude that Sca-1+ cells can differentiate into functional ECs
      via activation of HDAC3, accelerating re-endothelialization of injured arteries
      and reducing neointima formation.

PMID- 16902165
TI  - Effects of granulocyte colony simulating factor on functional activities of
      endothelial progenitor cells in patients with chronic ischemic heart disease.
AB  - OBJECTIVE: Bone marrow-derived circulating endothelial progenitor cells (EPCs)
      may contribute to regeneration of infarcted myocardium and enhance
      neovascularization. Granulocyte colony-stimulating factor (G-CSF) is well
      established to mobilize hematopoietic stem cells (HSCs) and might, thereby, also
      increase the pool of endogenously circulating EPC. Therefore, we investigated the
      effects of G-CSF administration on mobilization and functional activities of
      blood-derived EPC in patients with chronic ischemic heart disease (CIHD). METHODS
      AND RESULTS: Sixteen patients with CIHD received 10 microg/kg per day
      subcutaneous G-CSF injection for 5 days. Leukocyte counts, the number of HSCs and
      EPCs, and the migratory response to VEGF and SDF-1 were analyzed before and after
      G-CSF-therapy. At day 5 of G-CSF treatment, the number of circulating leukocytes,
      CD34+ CD45+ and CD34+ CD133+ cells was significantly increased. Likewise, G-CSF
      treatment augmented the numbers of colony forming units with endothelial cell
      morphology (EC-CFU). However, the functional activity of the EPC as assessed by
      the migratory response to VEGF and SDF-1 was significantly reduced after G-CSF
      treatment (P<0.01). Because G-CSF was previously shown to cleave the CXCR4
      receptor, we determined the surface expression of the 6H8 epitope of the CXCR4
      receptor by fluorescence-activated cell sorter (FACS) analysis. Consistent with
      the reduced migratory capacity, the surface expression of the functionally active
      CXCR4 receptor was significantly reduced. To test the functional activity of the
      cultivated EPCs in vivo, cells were intravenously infused in nude mice after hind
      limb ischemia. EPCs, which were cultivated before G-CSF administration, increased
      blood flow recovery and prevented limb necrosis. However, infusion of EPCs, which
      were isolated 5 days after G-CSF treatment from the same patient, showed a
      reduced capacity to augment blood flow recovery and to prevent necrosis by 27%.
      CONCLUSIONS: G-CSF treatment effectively mobilizes HSCs and EPCs. However, the
      migratory response to SDF-1 and in vivo capacity of G-CSF-mobilized EPCs was
      significantly reduced.

PMID- 16902166
TI  - Associations of PPARGC1A haplotypes with plaque score but not with intima-media
      thickness of carotid arteries in middle-aged subjects.
AB  - BACKGROUND AND PURPOSE: Peroxisome proliferator activated receptor gamma
      coactivator 1alpha (PGC-1alpha, PPARGC1A) integrates the transcriptional program
      of mitochondrial biogenesis. Mitochondria are the main source of cellular
      reactive oxygen species implicated in atherogenesis. We therefore ascertained
      associations of PPARGC1A polymorphisms with asymptomatic carotid atherosclerosis.
      METHODS: Eight single nucleotide polymorphisms tagging two haplotype blocks
      within PPARGC1A were studied in 1379 participants of the Salzburg Atherosclerosis
      Prevention Program in Subjects at High Individual Risk. Early atherosclerosis was
      assessed by intima-media thickness and extent of plaques (B-score) of the carotid
      arteries. RESULTS: No associations of carotid artery intima-media thickness
      measurements with block 1 or 2 haplotype distributions or individual haplotypes
      were observed. However, the block 1 haplotype carrying the variant C nucleotide
      at -3974 relative to the transcription start site was associated with disease
      status defined by the presence of more than one minimal lesion and the -3974 C
      allele was associated with decreased risk (odds ratio=0.60, P=0.007) after
      adjustment for linkage disequilibrium between single nucleotide polymorphisms.
      CONCLUSIONS: These result are consistent with the concept that risk factors for
      distinct carotid phenotypes may vary and suggest, but do not prove, that PGC
      1alpha may contribute to the regulation of atherogenic pathways.

PMID- 16902169
TI  - Interatrial shunt-associated migraine: serendipity, empiricism, hope, or hype?

PMID- 16902170
TI  - Treatment and clinical outcome in patients with basilar artery occlusion.

PMID- 16902171
TI  - Development of complex interventions in stroke care: a systematic review.
AB  - BACKGROUND AND PURPOSE: Stroke care is complex, requiring input from
      professionals, patients and carers. Identifying and developing appropriate
      intervention components to meet these complex needs is difficult. The Medical
      Research Council (MRC) Framework for developing and evaluating 'complex'
      (nonpharmacological) interventions aims to improve intervention development. This
      study uses the Framework to review complex interventions in stroke care. METHODS:
      Systematic review with multiple search strategies (electronic databases, recent
      journals, gray literature) was used. The MRC Framework was used to guide the
      search strategy and assess study quality. 'Complex interventions' were defined as
      educational/psychosocial interventions to change knowledge, beliefs or behaviors.
      RESULTS: Sixty-seven studies were included: 39 randomized controlled trials (RCT)
      and 28 other designs. Complex interventions targeted healthcare professionals
      (17), and patients, carers and the general population (21 targeting primary or
      secondary prevention; 30 targeting adjustment and recovery after stroke).
      Compared with recovery studies, primary and secondary prevention studies were
      significantly less likely to have been evaluated in RCTs. Interventions evaluated
      in RCTs were significantly less likely to influence primary outcomes (26%)
      compared with other designs (44%). Theoretical grounding to support intervention
      choice was reported in 40 studies but only 14 were theoretically 'well
      developed'; 21 RCTs listed multiple primary outcome measures, with 10 listing 5
      or more. Of these only 3 reported considering statistical power before
      recruitment and none was sufficiently powered. CONCLUSIONS: Few complex
      interventions in stroke care have been adequately developed or evaluated. This
      may explain failures to demonstrate efficacy. In future, greater attention is
      needed to theoretical development and methodological quality.

PMID- 16902172
TI  - Sinus venosus-type atrial septal defect: a rare curable cause of recurrent
      transient neurological deficits.
AB  - BACKGROUND AND PURPOSE: Sinus venosus defect is a rare cardiac abnormality,
      provoking an interatrial shunting outside the interatrial septum. Echographic
      diagnosis is difficult and may require examination by a specialized cardiologist.
      SUMMARY OF CASE: We report the case of a young woman who presented with repeated
      episodes of hemiparesis. CONCLUSIONS: Surgical correction of sinus venosus defect
      led to disappearance of neurological symptoms.

PMID- 16902173
TI  - White matter lesions are associated with progression of medial temporal lobe
      atrophy in Alzheimer disease.
AB  - BACKGROUND AND PURPOSE: Medial temporal lobe atrophy (MTA) is a hallmark of
      Alzheimer disease (AD). Its progression is often seen during the course of AD,
      but its frequency and risk factors remain unclear. METHODS: We investigated MTA
      in 35 patients with AD from whom sequential magnetic resonance imaging scans were
      available. White matter lesions (WML; for the periventricular [PV] and
      subcortical [SC] regions separately) and MTA were rated semiquantitatively.
      RESULTS: In approximately two thirds of all patients, progression of MTA was
      found. The mean MTA progression was 0.8 (standard deviation: 0.5) and 0.3
      (standard deviation: 0.4) for patients with or without PVWML at baseline
      (P=0.01). Patients who showed progression of PVWML over the course of their
      disease had a significantly higher mean progression of MTA than those without
      PVWML progression (0.9 [SD: 0.4]) and 0.4 [SD: 0.5]; P=0.01). Patients with PVWML
      at baseline had a 40-fold increased risk for progression of MTA compared with
      those without baseline PVWML (odds ratio=40.0, 95% CI=1.3 to 1.2x10(3), P=0.03).
      Patients with progression of PVWML during the course of the disease had an
      increased risk for MTA progression (odds ratio=3.7 per unit increase of
      progression of PVWML, 95% CI=1.1 to 12.9, P=0.04). There was higher risk for
      progression of MTA for those with progression of PVWML than those without (odds
      ratio=10.9, 95% CI=1.0 to 122.5, P=0.05). This was not found for SCWML.
      CONCLUSIONS: Our findings suggest that the presence and the progression of WML
      are associated with progression of MTA in AD. WML may be a predictor of the
      course of the disease and a potential treatment target in AD.

PMID- 16902174
TI  - Intravenous tissue plasminogen activator in patients with stroke increases the
      bioavailability of insulin-like growth factor-1.
AB  - BACKGROUND AND PURPOSE: Insulin-like growth factor (IGF)-1 has potent
      neuroprotective properties. We investigated the effects of intravenous
      administration of tissue plasminogen activator (tPA) on serum levels of IGF-1 and
      IGF-binding protein (IGFBP)-3 in patients with acute ischemic stroke. METHODS:
      Serum levels of total IGF-1, free IGF-1, and IGFBP-3 were measured by
      radioimmunoassay in 10 patients with ischemic stroke treated with intravenous tPA
      (0.9 mg/kg body weight) and 10 untreated controls. RESULTS: During tPA treatment,
      total IGF-1 and IGFBP-3 serum levels did not change, but there was an &70%
      increase in free IGF-1 serum levels from 0.98+/-0.25 at baseline to 1.69+/-0.18
      nmol/L at the end of the 1-hour infusion (P=0.01). CONCLUSIONS: Intravenous
      therapy with tPA enhances the bioavailability of IGF-1.

PMID- 16902175
TI  - Long-term effects of 6-week whole-body vibration on balance recovery and
      activities of daily living in the postacute phase of stroke: a randomized,
      controlled trial.
AB  - BACKGROUND AND PURPOSE: The long-term effects of 6-weeks whole-body vibration, as
      a novel method of somatosensory stimulation, on postural control and activities
      of daily living were compared with those of 6 weeks of exercise therapy on music
      of the same intensity in the postacute phase of stroke. METHODS: Fifty-three
      patients with moderate to severe functional disabilities were randomized within 6
      weeks poststroke and within 3 days after admission to a rehabilitation center to
      either whole-body vibration or exercise therapy on music in addition to a regular
      inpatient rehabilitation program. The whole-body vibration group received 4x45
      second stimulation on the Galileo 900 (30-Hz frontal plane oscillations of 3-mm
      amplitude) for 5 days per week during 6 weeks. The exercise therapy on music
      group received the same amount of exercise therapy on music. Outcome variables
      included the Berg Balance Scale, Trunk Control Test, Rivermead Mobility Index,
      Barthel Index, Functional Ambulation Categories, Motricity Index, and
      somatosensory threshold at 0, 6, and 12 weeks follow up. RESULTS: At baseline,
      both groups were comparable in terms of prognostic factors and outcome measures.
      Both at 6 and 12 weeks follow up, no clinically relevant or statistical
      differences in outcome were observed between the groups. No side effects were
      reported. CONCLUSIONS: Daily sessions of whole-body vibration during 6 weeks are
      not more effective in terms of recovery of balance and activities of daily living
      than the same amount of exercise therapy on music in the postacute phase of
      stroke.

PMID- 16902176
TI  - Carotid artery stenting: first consensus document of the ICCS-SPREAD Joint
      Committee.
AB  - BACKGROUND AND PURPOSE: The prevention of stroke and the correct treatment of
      carotid artery stenosis represent today a major debate in cardiovascular
      medicine. Beside carotid endarterectomy, carotid angioplasty and stenting is
      becoming more widely performed for the treatment of severe carotid obstructive
      disease, and is now accepted as a less invasive technique that may provide an
      alternative for selected patients, particularly those with significant
      comorbidities. An Italian multidisciplinary task force, in which converged the
      most representative scientific societies involved in carotid treatment, was
      created to provide neurologists, radiologist, cardiologists, vascular surgeons,
      and all those involved in prevention and treatment of carotid disease with a
      simple, clear and updated evidence-based consensus document. SUMMARY OF REVIEW:
      This First Consensus Document of the ICCS (Italian Consensus Carotid
      Stenting)/SPREAD group addressed the main issues related to methodology,
      definition of symptomatic and asymptomatic carotid stenosis, indication and
      procedures for carotid artery stenting, including the use of devices for
      preventing procedural embolic complications. Special attention was paid to
      credentials and competency for physicians qualifications to perform vascular
      angioplasty and stent placement, including training, acceptable complication
      rates and certification. CONCLUSIONS: As any guideline or consensus statement,
      also this document is valid as long as the evidence on which it is based remains
      up-to-date. In such a fast-evolving field of medicine as the management of
      carotid stenosis, it is mandatory to stimulate a continuous and fruitful
      discussion among all the professionals involved in this very evolutionary field.

PMID- 16902177
TI  - Spatially discordant alternans in cardiac tissue: role of calcium cycling.
AB  - Spatially discordant alternans, where the action potential duration (APD) and
      intracellular calcium transient (Ca(i)) alternate with opposite phase in
      different regions of tissue, is known to promote wave break and reentry. However,
      this phenomenon is not completely understood. It is known that alternans at the
      cellular level can be caused by dynamical instabilities arising from either
      membrane voltage (V(m)) attributable to steep APD restitution or to calcium (Ca)
      cycling. Here, we used a mathematical model of intracellular Ca cycling, coupled
      with membrane ion currents, to investigate the dynamics of V(m) and Ca(i)
      transient alternans in an isolated cell, in two electrotonically coupled cells,
      and in 1D spatially homogeneous tissue. Our main finding is a novel instability
      mechanism in which the bidirectional coupling of V(m) and Ca(i) can drive the
      Ca(i) transient of two neighboring cells to be out of phase. This instability is
      manifested in cardiac tissue by the dynamical formation of spatially discordant
      alternans. In this case, Ca(i) transient alternans can reverse phase over a
      length scale of one cell, whereas APD alternans reverses phase over a much longer
      length scale set by the electrotonic coupling. We analyze this mechanism in
      detail and show that it is a robust consequence of experimentally established
      properties of the bidirectional coupling between Ca cycling and V(m) dynamics.
      Finally, we address the experimental relevance of these findings and suggest
      physiological conditions under which these patterns can be observed.

PMID- 16902178
TI  - Activation of D3 dopamine receptor decreases angiotensin II type 1 receptor
      expression in rat renal proximal tubule cells.
AB  - The dopaminergic and renin angiotensin systems interact to regulate blood
      pressure. Disruption of the D(3) dopamine receptor gene in mice produces renin
      dependent hypertension. In rats, D(2)-like receptors reduce angiotensin II
      binding sites in renal proximal tubules (RPTs). Because the major D(2)-like
      receptor in RPTs is the D(3) receptor, we examined whether D(3) receptors
      regulate angiotensin II type 1 (AT(1)) receptors in rat RPT cells. The effect of
      D(3) receptors on AT(1) receptors was studied in vitro and in vivo. The D(3)
      receptor agonist PD128907 decreased AT(1) receptor protein and mRNA in WKY RPT
      cells and increased it in SHR cells. PD128907 increased D(3) receptors in WKY
      cells but had no effect in SHR cells. D(3)/AT(1) receptors colocalized in RPT
      cells; D(3) receptor stimulation decreased the percent amount of D(3) receptors
      that coimmunoprecipitated with AT(1) receptors to a greater extent in WKY than in
      SHR cells. However, D(3) receptor stimulation did not change the percent amount
      of AT(1) receptors that coimmunoprecipitated with D(3) receptors in WKY cells and
      markedly decreased the coimmunoprecipitation in SHR cells. The D(3) receptor also
      regulated the AT(1) receptor in vivo because AT(1) receptor expression was
      increased in kidneys of D(3) receptor-null mice compared with wild type
      littermates. D(3) receptors may regulate AT(1) receptor function by direct
      interaction with and regulation of AT(1) receptor expression. One mechanism of
      hypertension may be related to increased renal expression of AT(1) receptors due
      decreased D(3) receptor regulation.

PMID- 16902179
TI  - Myocyte-restricted focal adhesion kinase deletion attenuates pressure overload
      induced hypertrophy.
AB  - Focal adhesion kinase (FAK) is a ubiquitously expressed cytoplasmic tyrosine
      kinase strongly activated by integrins and neurohumoral factors. Previous studies
      have shown that cardiac FAK activity is enhanced by hypertrophic stimuli before
      the onset of overt hypertrophy. Herein, we report that conditional deletion of
      FAK from the myocardium of adult mice did not affect basal cardiac performance,
      myocyte viability, or myofibrillar architecture. However, deletion of FAK
      abolished the increase in left ventricular posterior wall thickness, myocyte
      cross-sectional area, and hypertrophy-associated atrial natriuretic factor
      induction following pressure overload. Myocyte-restricted deletion of FAK
      attenuated the initial wave of extracellular signal-regulated kinase activation
      and cFos expression induced by adrenergic agonists and biomechanical stress. In
      addition, we found that persistent challenge of mice with myocyte-restricted FAK
      inactivation leads to enhanced cardiac fibrosis and cardiac dysfunction in
      comparison to challenged genetic controls. These studies show that loss of FAK
      impairs normal compensatory hypertrophic remodeling without a concomitant
      increase in apoptosis in response to cardiac pressure overload and highlight the
      possibility that FAK activation may be a common requirement for the initiation of
      this compensatory response.

PMID- 16902180
TI  - An angiotensin II type 1 receptor mutant lacking epidermal growth factor receptor
      transactivation does not induce angiotensin II-mediated cardiac hypertrophy.
AB  - We have shown previously that tyrosine 319 in a conserved YIPP motif in the C
      terminus of angiotensin II (Ang II) type 1 receptors (AT(1)Rs) is essential for
      transactivation of epidermal growth factor receptor (EGFR) in vitro. We
      hypothesized that the signaling mechanism mediated through the specific amino
      acid sequence in the G protein-coupled receptor plays an important role in
      mediating cardiac hypertrophy in vivo. Transgenic mice with cardiac-specific
      overexpression of wild-type AT(1)R (Tg-WT) and an AT(1)R with a mutation in the
      YIPP motif (Tg-Y319F) were studied. Tg-Y319F mice developed no significant
      cardiac hypertrophy, in contrast to the significant development of hypertrophy in
      Tg-WT mice. Expression of fetal-type genes, such as atrial natriuretic factor,
      was also significantly lower in Tg-Y319F than in Tg-WT mice. Infusion of Ang II
      caused an enhancement of hypertrophy in Tg-WT mice but failed to induce
      hypertrophy in Tg-Y319F mice. Left ventricular myocardium in Tg-Y319F mice
      developed significantly less apoptosis and fibrosis than that in Tg-WT mice. EGFR
      phosphorylation was significantly inhibited in Tg-Y319F mice, confirming that
      EGFR was not activated in Tg-Y319F mouse hearts. In contrast,
      activation/phosphorylation of protein kinase C, STAT3, extracellular signal
      regulated kinase, and Akt and translocation of Galphaq/11 to the cytosolic
      fraction were maintained in Tg-Y319F hearts. Furthermore, a genetic cross between
      Tg-WT and transgenic mice with cardiac-specific overexpression of dominant
      negative EGFR mimicked the phenotype of Tg-Y319F mice. In conclusion,
      overexpression of AT(1)-Y319F in cardiac myocytes diminished EGFR transactivation
      and inhibited a pathological form of cardiac hypertrophy. The YIPP motif in the
      AT(1)R plays an important role in mediating cardiac hypertrophy in vivo.

PMID- 16902181
TI  - Thermoregulation and aging.

PMID- 16902182
TI  - Hypocretin/orexin type 1 receptor in brain: role in cardiovascular control and
      the neuroendocrine response to immobilization stress.
AB  - Hypocretin/orexin acts pharmacologically in the hypothalamus to stimulate stress
      hormone secretion at least in part by an action in the hypothalamic
      paraventricular nucleus, where the peptide's receptors have been localized. In
      addition, orexin acts in the brain to increase sympathetic tone and, therefore,
      mean arterial pressure and heart rate. We provide evidence for the role of
      endogenously produced hypocretin/orexin in the physiological response to
      immobilization stress and identify the receptor subtype responsible for this
      action of the peptide. Antagonism of the orexin type 1 receptor (OX(1)R) in the
      brain prevented the ACTH-stimulating effect of centrally administered
      hypocretin/orexin. Furthermore, pretreatment of animals with the OX(1)R
      antagonist blocked the ACTH response to immobilization/restraint stress. The
      OX(1)R antagonist did not, however, block the pharmacological or physiological
      release of prolactin in these two models. Antagonism of the OX(1)R also blocked
      the central action of orexin to elevate mean arterial pressures and heart rates
      in conscious rats. These data suggest receptor subtype-selective responses to
      hypocretin/orexin and provide further evidence for the importance of endogenously
      produced peptide in the physiological control of stress hormone secretion.

PMID- 16902183
TI  - Lesions of the anteroventral third ventricle region exaggerate neuroendocrine and
      thermogenic but not behavioral responses to a novel environment.
AB  - Mild psychological stressors provoke an acute rise in core temperature (T(C)),
      stimulate the hypothalamo-pituitary-adrenocortical (HPA) axis, and induce various
      stress-related behaviors. In the present study, we examined the effect of
      ablation of the anteroventral third ventricle region (AV3V) on both physiological
      and behavioral responses to a novel environment. T(C) was monitored in male
      Sprague-Dawley rats, with either sham or AV3V lesions, during a 5-h exposure to a
      novel environment. Trunk blood was collected, in a second group of rats, for the
      assessment of plasma levels of ACTH and corticosterone. Novelty-induced grooming
      and rearing behaviors were assessed in a third group of animals. T(C) was
      elevated in all animals after 30 min in the novel environment, but the rise was
      exaggerated in rats with AV3V lesions ( approximately 0.5 degrees C). AV3V-lesion
      rats maintained a higher core temperature for 2 h before it returned to the same
      level as the control group. Plasma levels of ACTH and corticosterone were also
      exaggerated in the AV3V lesion group after 30 min in a novel environment. In
      contrast to the physiological responses, the behavioral measures of grooming and
      rearing revealed no differences between the groups. The results from the current
      study suggest that neurons within the AV3V region exert an inhibitory influence
      on the HPA axis and fever developed in response to stressful psychological
      stimuli. They also confirm that the physiological and hormonal components of the
      stress response are independent of certain behavioral measures of stress.

PMID- 16902184
TI  - Pifithrin-alpha, an inhibitor of p53 transactivation, alters the inflammatory
      process and delays tendon healing following acute injury.
AB  - Transcription factor p53, which was initially associated with cancer, has now
      emerged as an important regulator of inflammation and extracellular matrix
      homeostasis, two processes highly relevant to tendon repair. The goal of this
      study was to evaluate the effect of a p53 transactivation inhibitor, namely,
      pifithrin-alpha, on the pathophysiological sequence following collagenase-induced
      tendon injury. Administration of pifithrin-alpha during the inflammatory phase
      reduced the accumulation of neutrophils and macrophages by 30 and 40%,
      respectively, on day 3 postinjury. Pifithrin-alpha failed to reduce the
      percentage of apoptotic cells following collagenase injection but delayed
      functional recovery. In uninjured Achilles tendons, pifithrin-alpha increased
      metalloprotease activity 2.4-fold. Accordingly, pifithrin-alpha reduced the
      collagen content in intact tendons as well as in injured tendons 7 days
      posttrauma compared with placebo. The effect of pifithrin-alpha on load to
      failure and stiffness was also evaluated. The administration of pifithrin-alpha
      during the inflammatory phase did not significantly decrease the functional
      deficit 3 days posttrauma. More importantly, load to failure and stiffness were
      significantly decreased in the pifithrin-alpha group from day 7 to day 28
      compared with placebo. Overall, our results suggest that administration of
      pifithrin-alpha alters the inflammatory process and delays tendon healing. The
      present findings also support the concept that p53 can regulate extracellular
      matrix homeostasis in vivo.

PMID- 16902185
TI  - Immunological memory is compromised by food restriction in deer mice Peromyscus
      maniculatus.
AB  - The immune system protects organisms against infection, but this protection
      presumably comes at a cost. Here, we asked whether food restriction would
      compromise the ability of an organism to generate an immune response on
      reexposure to an antigen, which would represent a functional cost of
      immunological memory. Immunological memory is generated when B and T lymphocytes
      sensitive to components of pathogens (i.e., antigens) proliferate after exposure
      and persist in circulation to hinder reinfection. To test the possibility that B
      cell memory, the component of the immune system responsible for antibody
      production, is expensive to maintain, secondary antibody production against a
      novel protein [keyhole limpet hemocyanin (KLH)] was compared in food-restricted
      and ad libitum-fed male deer mice (Peromyscus maniculatus). To determine whether
      compromised secondary antibody production was solely due to elevated
      corticosterone independent of resource availability, some food-restricted and ad
      libitum-fed mice were subjected to unpredictable, chronic (2 h/day) restraint.
      Mice fed 70% of their ad libitum diet 2 wk after primary antigen challenge
      produced approximately 95% less IgG against KLH after a second antigen challenge
      than mice fed ad libitum, even though all mice were fed ad libitum during the
      secondary antibody response period. Restraint had no effect on secondary IgG
      production in response to KLH, and corticosterone concentrations 1 day after food
      restriction did not differ between food-restricted and ad libitum-fed mice.
      Together, these data imply that secondary antibody responses and the benefits of
      immunological memory are energetically costly in this species.

PMID- 16902186
TI  - Insulin sensitivity, fat distribution, and adipocytokine response to different
      diets in lean and obese cats before and after weight loss.
AB  - Obesity is a major health problem in cats and a risk factor for diabetes. It has
      been postulated that cats are always gluconeogenic and that the rise in obesity
      might be related to high dietary carbohydrates. We examined the effect of a high
      carbohydrate/low-protein (HC) and a high-protein/low-carbohydrate (HP) diet on
      glucose and fat metabolism during euglycemic hyperinsulinemic clamp,
      adipocytokines, and fat distribution in 12 lean and 16 obese cats before and
      after weight loss. Feeding diet HP led to greater heat production in lean but not
      in obese cats. Regardless of diet, obese cats had markedly decreased glucose
      effectiveness and insulin resistance, but greater suppression of nonesterified
      fatty acids during the euglycemic hyperinsulinemic clamp was seen in obese cats
      on diet HC compared with lean cats on either diet or obese cats on diet HP. In
      contrast to humans, obese cats had abdominal fat equally distributed
      subcutaneously and intra-abdominally. Weight loss normalized insulin sensitivity;
      however, increased nonesterified fatty acid suppression was maintained and fat
      loss was less in cats on diet HC. Adiponectin was negatively and leptin
      positively correlated with fat mass. Lean cats and cats during weight loss, but
      not obese cats, adapted to the varying dietary carbohydrate/protein content with
      changes in substrate oxidation. We conclude that diet HP is beneficial through
      maintenance of normal insulin sensitivity of fat metabolism in obese cats,
      facilitating the loss of fat during weight loss, and increasing heat production
      in lean cats. These data also show that insulin sensitivity of glucose and fat
      metabolism can be differentially regulated in cats.

PMID- 16902187
TI  - Increased maternal cortisol in late-gestation ewes decreases fetal cardiac
      expression of 11beta-HSD2 mRNA and the ratio of AT1 to AT2 receptor mRNA.
AB  - Moderately elevated maternal cortisol levels late in gestation cause enlargement
      of the fetal sheep heart. We have used quantitative real-time PCR to examine
      expression of candidate genes in fetal hearts from mothers in whom cortisol
      levels were increased (by infusion of 1 mg cortisol.kg(-1).day(-1)) or decreased
      (by adrenalectomy and replacement to 0.5 mg cortisol.kg(-1).day(-1)) from 115 to
      130 days gestation. Control ewes were not treated with steroid. Expression of
      mineralocorticoid receptor (MR), glucocorticoid receptor (GR), 11beta
      hydroxysteroid dehydrogenases 1 and 2 (11beta-HSD1 and -2), IGF I and II, IGF
      receptors 1 and 2 (IGF-1R and IGF-2R), endothelial nitric oxide synthase, VEGF,
      myotrophin, angiotensinogen, the angiotensin receptors 1 and 2 (AT1R and AT2R),
      and the angiotensin converting enzymes 1 and 2 were measured. MR mRNA abundance
      in fetal hearts was found to be similar to that in adult kidney and hippocampus.
      Although there were no significant changes in most genes, 11beta-HSD2 and IGF-1R
      expression were significantly decreased in the high cortisol group and 11beta
      HSD2 expression negatively correlated to left ventricular wall thickness. There
      was also a significant change in the ratio of AT receptor expression, with
      increased AT2R and decreased AT1R in the high cortisol group. MR, GR, and 11beta
      HSD1 immunoreactivity was found in cardiomyocytes and cardiac blood vessels in
      126-128 day fetal sheep; in contrast 11beta-HSD2 staining was predominantly in
      blood vessels. These results indicate that cortisol could indeed act in the fetal
      heart to induce enlargement and suggest that the renin-angiotensin system may
      play a role.

PMID- 16902189
TI  - Gastrointestinal processing of Na+, Cl-, and K+ during digestion: implications
      for homeostatic balance in freshwater rainbow trout.
AB  - The role of the gastrointestinal tract in maintaining ionic homeostasis during
      digestion, as well as the relative contribution of the diet for providing
      electrolytes, has been generally overlooked in many aquatic species. An
      experimental diet that contained an inert reference marker (lead-glass beads) was
      used to quantify the net transport of Na(+), K(+), and Cl(-) during the digestion
      and absorption of a single meal (3% ration) by freshwater rainbow trout
      (Oncorhynchus mykiss). Secretion of Cl(-) into the stomach peaked at 8 and 12 h
      following feeding at a rate of 1.1 mmol.kg(-1).h(-1), corresponding to a
      theoretical pH of 0.6 in the secreted fluid (i.e., 240 mmol/l HCl). The majority
      ( approximately 90%) of dietary Na(+) and K(+) was absorbed in the stomach,
      whereas subsequent large fluxes of Na(+) and Cl(-) into the anterior intestine
      corresponded to a large flux of water previously observed. The estimated
      concentration of Na(+) in fluids secreted into the anterior intestine was
      approximately 155 mmol/l, equivalent to reported hepatic bile values, whereas the
      estimated concentration of Cl(-) ( approximately 285 mmol/l) suggested seepage of
      HCl acid from the stomach in advance of the chyme front. Net absorption of K(+)
      in the stomach occurred following the cessation of Cl(-) secretion, providing
      indirect evidence of K(+) involvement with HCl acid production. Overall, 80-90%
      of the K(+) and Cl(-) contents of the meal were absorbed on a net basis, whereas
      net Na(+) absorption was negligible. Chyme-to-plasma ion concentration gradients
      were often opposed to the direction of ion transport, especially for Na(+) and
      Cl(-).

PMID- 16902188
TI  - Mechanism of oleoylethanolamide on fatty acid uptake in small intestine after
      food intake and body weight reduction.
AB  - The increase in the prevalence of human obesity highlights the need to identify
      molecular and cellular mechanisms involved in control of feeding and energy
      balance. Oleoylethanolamide (OEA), an endogenous lipid produced primarily in the
      small intestine, has been identified to play an important role in the regulation
      of animal food intake and body weight. Previous studies indicated that OEA
      activates peroxisome proliferator-activated receptor-alpha, which is required to
      mediate the effects of appetite suppression, reduces blood lipid levels, and
      enhances peripheral fatty acid catabolism. However, the effect of OEA on
      enterocyte function is unclear. In this study, we have examined the effect of OEA
      on intestinal fatty acid uptake and FAT/CD36 expression in vivo and in vitro. We
      intraperitoneally administered OEA to rats and examined FAT/CD36 mRNA level and
      fatty acid uptake in enterocytes isolated from the proximal small intestine, as
      well as in adipocytes. Our results indicate that OEA treatment significantly
      increased FAT/CD36 mRNA expression in intestinal mucosa and isolated jejunal
      enterocytes. In addition, we also found that OEA treatment significantly
      increases fatty acid uptake in isolated enterocytes in vitro. These results
      suggest that in addition to appetite regulation, OEA may regulate body weight by
      altered peripheral lipid metabolism, including increased lipolysis in adipocytes
      and enhanced fatty acid uptake in enterocytes, both in conjunction with increased
      expression of FAT/CD36. This study may have important implications in
      understanding the mechanism of OEA in the regulation of fatty acid absorption in
      human physiological and pathophysiological conditions.

PMID- 16902190
TI  - Low-carbohydrate diets affect energy balance and fuel homeostasis differentially
      in lean and obese rats.
AB  - In parallel with increased prevalence of overweight people in affluent societies
      are individuals trying to lose weight, often using low-carbohydrate diets.
      Nevertheless, long-term metabolic consequences of those diets, usually high in
      (saturated) fat, remain unclear. Therefore, we investigated long-term effects of
      high-fat diets with different carbohydrate/protein ratios on energy balance and
      fuel homeostasis in obese (fa/fa) Zucker and lean Wistar rats. Animals were fed
      high-carbohydrate (HC), high-fat (HsF), or low-carbohydrate, high-fat, high
      protein (LC-HsF-HP) diets for 60 days. Both lines fed the LC-HsF-HP diet
      displayed reduced energy intake compared with those fed the HsF diet (Zucker, 
      3.7%) or the HC diet (Wistar rats, -12.4%). This was not associated with lower
      weight gain relative to HC fed rats, because of increased food efficiencies in
      each line fed HsF and particularly LC-HsF-HP food. Zucker rats were less glucose
      tolerant than Wistar rats. Lowest glucose tolerances were found in HsF and
      particularly in LC-HsF-HP-fed animals irrespective of line, but this paralleled
      reduced plasma adiponectin levels, elevated plasma resistin levels, higher
      retroperitoneal fat masses, and reduced insulin sensitivity (indexed by insulin
      induced hypoglycemia) only in Wistar rats. In Zucker rats, however, improved
      insulin responses during glucose tolerance testing and tendency toward increased
      insulin sensitivities were observed with HsF or LC-HsF-HP feeding relative to HC
      feeding. Thus, despite adverse consequences of LC-HsF diets on blood glucose
      homeostasis, principal differences exist in the underlying hormonal regulatory
      mechanisms, which could have benefits for B-cell functioning and insulin action
      in the obese state but not in the lean state.

PMID- 16902191
TI  - Variations in apparent mass of mammalian fast-type myosin light chains correlate
      with species body size, from shrew to elephant.
AB  - A recent study (Bicer S and Reiser PJ. J Muscle Res Cell Motil 25: 623-633, 2004)
      suggested considerable variation in the apparent molecular mass (M(a)), deduced
      from electrophoretic mobility, in fast-type myosin light chains (MLCF),
      especially MLC1F, among mammalian species. Furthermore, there was an indication
      that MLC1F M(a) generally correlates with species body mass, over an
      approximately 4,000-fold range in body mass. The results also suggested that M(a)
      of other low-molecular-weight myofibrillar proteins is less variable and not as
      strongly correlated with body mass among the same species. The objective of this
      study was to test the hypotheses that the M(a) of MLCs does, in fact, vary and
      correlate with species body mass. The electrophoretic mobilities of MLCF isoforms
      from 19 species, varying in size approximately 500,000-fold, were quantitated.
      The results confirm that the M(a) of MLC1F and MLC2F vary significantly among
      mammals, spanning a very broad range in body mass; the MLC1F M(a) varies more
      than that of other low-molecular-weight myofibrillar proteins; and there is a
      significant correlation between species body mass and MLC1F M(a). Differences in
      MLC1F M(a) among five species can be accounted for by differences in the reported
      amino acid sequence, especially the length of a common polyalanine region near
      the NH(2)-terminal actin-binding site. The possibility that the differences in
      MLC1F sequence among mammalian species, in and adjacent to the actin-binding
      region, are related to differences in modulation of cross-bridge kinetics in
      species with diverse locomotion kinetics is discussed.

PMID- 16902192
TI  - Silica-directed mast cell activation is enhanced by scavenger receptors.
AB  - Inhalation of crystalline silica results in pulmonary fibrosis and silicosis. It
      has been suggested that mast cells play a role in these conditions. How mast
      cells would influence pathology is unknown. We thus explored mast cell
      interactions with silica in vitro and in B6.Cg-kit(W-sh) mast cell-deficient
      mice. B6.Cg-kit(W-sh) mice did not develop inflammation or significant collagen
      deposition after instillation of silica, while C57Bl/6 wild-type mice did have
      these findings. Given this supporting evidence of a role for mast cells in the
      development of silicosis, we examined the ability of silica to activate mouse
      bone marrow-derived mast cells (BMMC), including degranulation (beta
      hexosaminidase release); production of reactive oxygen species (ROS) and
      inflammatory mediators; and the effects of silica on Fc epsilon RI-dependent
      activation. Silica did not induce mast cell degranulation. However, TNF-alpha, IL
      13, monocyte chemotactic protein-1, protease activity, and production of ROS were
      dose-dependently increased after silica exposure, and production was enhanced
      after Fc epsilon RI stimulation. This mast cell activation was inhibited by anti
      inflammatory compounds. As silica mediates some effects in macrophages through
      scavenger receptors (SRs), we first determined that mast cells express scavenger
      receptors; then explored the involvement of SR-A and macrophage receptor with
      colleagenous structure (MARCO). Silica-induced ROS formation, apoptosis, and TNF
      alpha production were reduced in BMMC obtained from SR-A, MARCO, and SR-A/MARCO
      knockout mice. These findings demonstrate that silica directs mast cell
      production of inflammatory mediators, in part through SRs, providing insight into
      critical events in the pathogenesis and potential therapeutic targets in
      silicosis.

PMID- 16902194
TI  - Muscarinic receptors mediate stimulation of human lung fibroblast proliferation.
AB  - Airway remodeling is a structural alteration associated with chronic inflammatory
      and obstructive airway diseases, wherein fibroblasts are crucially involved. The
      present study investigates whether lung fibroblast proliferation is influenced by
      muscarinic mechanisms. For this purpose, expression of muscarinic receptors in
      MRC-5 human lung fibroblasts was characterized by semiquantitative RT-PCR, and
      the effects of muscarinic agonists and antagonists on ((3)H)-thymidine
      incorporation as a measure of proliferative activity were studied under different
      culture conditions. MRC-5 fibroblasts express mRNA encoding different subtypes of
      muscarinic receptors (M(2) > M(3) > M(4), traces for M(5) and no M(1)).
      Expression of M(2) and M(3) receptors was confirmed at the protein level by
      immunoblot analysis. Under different culture conditions, carbachol (up to 10
      microM) or oxotremorine (10 microM) stimulated ((3)H)-thymidine incorporation,
      with maximum increases between about 40 and 100%. The stimulatory effect of 10
      microM carbachol was prevented by pretreatment with pertussis toxin and
      antagonized in a concentration-dependent manner by the muscarinic receptor
      antagonists tiotropium, AQ-RA 741, AF-DX 384, 4-diphenylacetoxy-N
      methylpiperidine methoiodide, himbacine, p-fluorohexahydrosiladifenidol, and
      pirenzepine, with concentrations producing 50% inhibition of 14 pM, 24, 64, 127,
      187, 452 nM, and 1.5 microM, respectively. Primary human lung fibroblasts were
      also found to express mRNA for muscarinic receptors (M(2) > M(1) > M(3), traces
      for M(4) and no M(5)), and showed a pertussis toxin-sensitive proliferative
      response to muscarinic receptor stimulation. In conclusion, proliferation of
      human lung fibroblasts can be stimulated by activation of muscarinic receptors
      with a pharmacologic profile correlating best to M(2) receptors.

PMID- 16902195
TI  - Role of toll-like receptors on human adipose-derived stromal cells.
AB  - Adult mesenchymal stem cells (MSCs) are promising tools for such applications as
      tissue engineering and cellular therapy. It is not clear how stem cells exposed
      to unfavorable conditions (e.g., hypoxia or inflammation) respond to signals of
      danger after in vivo transplantation. Toll-like receptors (TLRs) play a major
      role in the immune system, participating in the initial recognition of microbial
      pathogens and pathogen-associated components. This study was designated to
      determine the role of TLRs in human MSCs. Reverse transcriptase-polymerase chain
      reaction (RT-PCR) and flow cytometry analysis demonstrated that MSCs derived from
      human adipose tissue and bone marrow express TLR-1, TLR-2, TLR-3, TLR-4, TLR-5,
      TLR-6, and TLR-9. We investigated induction of the differentiation and
      proliferation of human adipose tissue stromal cells (hADSCs) by TLR agonists,
      including flagellin, peptidoglycans (PGN), lipopolysaccharide (LPS), the
      synthetic double-stranded RNA analog poly(I:C), and synthetic CpG
      oligodeoxydinucleotide (CpG-ODN). None of these agonists, except ODN, affected
      the proliferation of hADSCs. LPS and PGN increased osteogenic differentiation,
      but CpG-ODN decreased it. Poly(I:C) itself did not affect adipogenic or
      osteogenic differentiations, but exerted a synergistic effect on LPS- or PGN
      induced osteogenic differentiation. RT-PCR analysis demonstrated that LPS and PGN
      induce osteogenic markers in hADSCs. TLR agonists affected the expression of
      chemokines and cytokines differentially. Furthermore, hADSCs affected the
      expression of specific TLRs in vitro under hypoxic conditions. These data provide
      evidence of a nonimmune role for TLR signaling on MSCs and may provide clues to
      the behavior of transplanted MSCs in vivo.

PMID- 16902193
TI  - Surfactant protein D augments bacterial association but attenuates major
      histocompatibility complex class II presentation of bacterial antigens.
AB  - Surfactant protein D (SP-D) is a secreted pattern recognition molecule associated
      with lung surfactant and mediates the clearance of pathogens in multiple ways. SP
      D is an established part of the innate immune system, but it also modulates the
      adaptive immune response by interacting with both antigen-presenting cells and T
      cells. In a previous study, antigen presentation by bone marrow-derived dendritic
      cells was enhanced by SP-D. As dendritic cell function varies depending on the
      tissue of origin, we extended these studies to antigen-presenting cells isolated
      from mouse lung. Flow cytometric studies showed that SP-D binds calcium
      dependently and specifically to lung CD11c-positive cells. Opsonization of
      fluorescently labeled Escherichia coli by SP-D enhanced uptake by lung dendritic
      cells. SP-D facilitated the association of E. coli and antigen-presenting cells
      by increasing the frequency of CD11+ cells associated with E. coli by up to 10
      fold. In contrast to the effect on bone marrow-derived dendritic cells, SP-D
      decreased the antigen presentation of ovalbumin, expressed in E. coli, to
      ovalbumin-specific major histocompatibility complex class II-specific T-cell
      hybridomas by 30-50%. The reduction of antigen presentation did not depend on
      whether the dendritic cells were isolated from the lungs of nonstimulated mice or
      mice that had been exposed to LPS aerosols. Our results show that SP-D increases
      the opsonization of pathogens, but decreases the antigen presentation by lung
      dendritic cells, and thereby, potentially dampens the activation of T cells and
      an adaptive immune response against bacterial antigens--during both steady-state
      conditions and inflammation.

PMID- 16902196
TI  - Nucleofection is the most efficient nonviral transfection method for neuronal
      stem cells derived from ventral mesencephali with no changes in cell composition
      or dopaminergic fate.
AB  - Neuronal progenitor cells (NPCs) play an important role in potential regenerative
      therapeutic strategies for neurodegenerative diseases, such as Parkinson disease.
      However, survival of transplanted cells is, as yet, limited, and the
      identification of grafted cells in situ remains difficult. The use of NPCs could
      be more effective with regard to a better survival and maturation when
      transfected with one or more neurotrophic factors. Therefore, we investigated the
      possibility of transfecting mesencephalic neuronal progenitors with different
      constructs carrying neurotrophic factors or the expression reporters enhanced
      green fluorescence protein (EGFP) and red fluorescent protein (DsRed). Different
      techniques for transfection were compared, and the highest transfection rate of
      up to 47% was achieved by nucleofection. Mesencephalic neuronal progenitors
      survived the transfection procedure; 6 hours after transfection, viability was
      approximately 40%, and the transfected cells differentiated into, for example,
      tyrosine hydroxylase-positive neurons. Within the group of transfected cells,
      many progenitors and several neurons were found. To provide the progenitor cells
      with a neurotrophic factor, different isoforms of fibroblast growth factor-2 were
      introduced. To follow the behavior of the transfected cells in vitro, functional
      tests such as the cell viability assay (water-soluble tetrazolium salt assay [WST
      1]) and the cell proliferation assay (5-bromo-2'-deoxyuridine-enzyme-linked
      immunosorbent assay) were performed. In addition, these transfected NPCs were
      viable after transplantation, expressed tyrosine hydroxylase in vivo, and could
      easily be detected within the host striatum because of their EGFP expression.
      This study shows that genetic modification of neural progenitors could provide
      attractive perspectives for new therapeutic concepts in neurodegenerative
      diseases.

PMID- 16902197
TI  - Aqueous humor enhances the proliferation of rat retinal precursor cells in
      culture, and this effect is partially reproduced by ascorbic acid.
AB  - Aqueous humor has been shown to influence the proliferation of various ocular
      cell types, but the effect on immature retinal cells is not known. Here, the
      effect of pig aqueous humor on the proliferation of rat retinal precursor cells
      (RPCs) was investigated. RPCs were prepared from embryonic day 19 Sprague-Dawley
      rats and cultured in the presence or absence of aqueous humor from healthy pigs
      along with a medium consisting of Dulbecco's modified Eagle's medium:Ham's F-12
      medium, N2 supplement, and epidermal growth factor. Proliferation was quantified
      by [(3)H]thymidine incorporation under different treatment conditions, and any
      associated morphological changes were noted. Potential active components of
      porcine aqueous humor were partially characterized by gel filtration
      chromatography, and the effect on RPC proliferation was determined. Results
      showed that adding 20% aqueous humor increased [(3)H]thymidine incorporation by
      as much as 317%, as compared with controls. Aqueous supplementation also
      increased both the number and size of RPC spherical aggregates ("spheres") over
      the first 4 days, consistent with increased proliferative activity. Using gel
      filtration and the in vitro proliferation assay, the growth-promoting activity of
      aqueous humor was localized to two different molecular mass ranges, namely,
      around 30 kDa and less than 1 kDa. Ascorbic acid was present in the lower
      molecular mass fraction, and use of this molecule reproduced some, but not all,
      of the proliferative activity present in aqueous humor. These results highlight
      the potential role of soluble factors present in the cellular microenvironment
      with respect to modulation of endogenous progenitor cell activity.

PMID- 16902198
TI  - Functional neuronal differentiation of bone marrow-derived mesenchymal stem
      cells.
AB  - Recent results have shown the ability of bone marrow cells to migrate in the
      brain and to acquire neuronal or glial characteristics. In vitro, bone marrow
      derived MSCs can be induced by chemical compounds to express markers of these
      lineages. In an effort to set up a mouse model of such differentiation, we
      addressed the neuronal potentiality of mouse MSCs (mMSCs) that we recently
      purified. These cells expressed nestin, a specific marker of neural progenitors.
      Under differentiating conditions, mMSCs display a distinct neuronal shape and
      express neuronal markers NF-L (neurofilament-light, or neurofilament 70 kDa) and
      class III beta-tubulin. Moreover, differentiated mMSCs acquire neuron-like
      functions characterized by a cytosolic calcium rise in response to various
      specific neuronal activators. Finally, we further demonstrated for the first time
      that clonal mMSCs and their progeny are competent to differentiate along the
      neuronal pathway, demonstrating that these bone marrow-derived stem cells share
      characteristics of widely multipotent stem cells unrestricted to mesenchymal
      differentiation pathways.

PMID- 16902199
TI  - Engineered xyloglucan specificity in a carbohydrate-binding module.
AB  - The field of plant cell wall biology is constantly growing and consequently so is
      the need for more sensitive and specific probes for individual wall components.
      Xyloglucan is a key polysaccharide widely distributed in the plant kingdom in
      both structural and storage tissues that exist in both fucosylated and non
      fucosylated variants. Presently, the only xyloglucan marker available is the
      monoclonal antibody CCRC-M1 that is specific to terminal alpha-1,2-linked fucosyl
      residues on xyloglucan oligo- and polysaccharides. As a viable alternative to
      searches for natural binding proteins or creation of new monoclonal antibodies,
      an approach to select xyloglucan-specific binding proteins from a combinatorial
      library of the carbohydrate-binding module, CBM4-2, from xylanase Xyn10A of
      Rhodothermus marinus is described. Using phage display technology in combination
      with a chemoenzymatic method to anchor xyloglucan to solid supports, the
      selection of xyloglucan-binding modules with no detectable residual wild-type
      xylan and beta-glucan-binding ability was achieved.

PMID- 16902201
TI  - Health care productivity.

PMID- 16902200
TI  - Antibiotics for upper respiratory tract infections and conjunctivitis in primary
      care.

PMID- 16902202
TI  - Postoperative nausea and vomiting.

PMID- 16902203
TI  - Heat waves and health protection.

PMID- 16902204
TI  - Governance of research that uses identifiable personal data.

PMID- 16902205
TI  - FDA appointment is stalled as revelations emerge over Plan B.

PMID- 16902206
TI  - Stroke services could do better.

PMID- 16902207
TI  - Pathology services are to be overhauled.

PMID- 16902208
TI  - Violence in Darfur region is jeopardising world's largest aid operation.

PMID- 16902209
TI  - Canadian medical journal faces threat from new online rival.

PMID- 16902211
TI  - Young people with HIV in Romania face discrimination.

PMID- 16902212
TI  - Rockets land around hospital in Haifa.

PMID- 16902213
TI  - Aid convoys are hampered by destroyed roads and bridges.

PMID- 16902214
TI  - Infective endocarditis.

PMID- 16902215
TI  - Ulcerative colitis: diagnosis and management.

PMID- 16902217
TI  - Assessment of generalisability in trials of health interventions: suggested
      framework and systematic review.

PMID- 16902218
TI  - Balancing potential risks and benefits of using confidential data.

PMID- 16902220
TI  - Whooping cough is quite common and can be diagnosed clinically.

PMID- 16902221
TI  - Fluoroquinolone resistance in Salmonella Typhi.

PMID- 16902222
TI  - What works in schizophrenia: cognitive behaviour therapy is not effective.

PMID- 16902223
TI  - What works in schizophrenia: depot preparations may improve outcomes.

PMID- 16902224
TI  - An independent NHS? Suffering from files.

PMID- 16902225
TI  - An independent NHS? Towards evidence based changes in NHS in all UK countries.

PMID- 16902226
TI  - An independent NHS? There is no "UK health service".

PMID- 16902227
TI  - An independent NHS? Why it really is time to separate from direct government
      involvement.

PMID- 16902228
TI  - Abstracts of the 50th Annual Scientific Meeting of the UK Society for Social
      Medicine. September 13-15, 2006. Leeds, United Kingdom.

PMID- 16902230
TI  - Corticosteroids reduce the tensile strength of isolated collagen fascicles.
AB  - BACKGROUND: Overuse tendon injuries are frequent. Corticosteroid injections are
      commonly used as treatment, although their direct effects on the material
      properties of the tendon are poorly understood. PURPOSE: To examine the influence
      of corticosteroids on the tensile strength of isolated collagen fascicles. STUDY
      DESIGN: Controlled laboratory study. METHODS: Single strands (300-500 mum) of rat
      tail collagen fascicles were incubated in either high (1 mL of 40 mgmL(-1) mixed
      with 0.5 mL saline 9%) or low (1 mL of 40 mgmL(-1) mixed with 2 mL saline 9%)
      concentration of methylprednisolone acetate (Depomedrol) for 3 or 7 days, while
      the control segment from the same fascicle was kept in saline (N = 64). After the
      incubation period, the fascicles underwent displacement to failure in a
      mechanical test rig at 0.13 mm/s, and thereafter hydroxylysyl pyridinoline and
      lysyl pyridinoline cross-link content was evaluated in a high-performance liquid
      chromatography system. Data for each group were analyzed with a 2-way analysis of
      variance (time x incubation) for ultimate stress (mean +/- standard deviation).
      RESULTS: In the high-concentration groups, strength was reduced after 3 (16.6 +/-
      4.6 MPa) and 7 (8.6 +/- 1.7 MPa) days compared to the controls (30.2 +/- 5.0 MPa
      and 25.6 +/- 4.6 MPa, respectively; P < .05). In the low-concentration groups,
      strength was reduced after 3 (12.0 +/- 3.1 MPa) and 7 days (10.9 +/- 2.5 MPa)
      compared to the controls (31.5 +/- 5.0 MPa and 32.4 +/- 5.6 MPa, respectively; P
      < .05). The amount of cross-linking was unaffected by the intervention.
      CONCLUSION: Data show that the tensile strength of isolated fascicles is markedly
      reduced after 3- and 7-day incubation in both high and low concentration of
      corticosteroids, although the observed effect on whole tendon remains unknown.
      CLINICAL RELEVANCE: Corticosteroids may weaken specific regions of the injected
      tendon and leave it more prone to rupture. This weakening effect is manifested in
      the individual collagen fascicles that constitute the tendon.

PMID- 16902231
TI  - Interaction of arch type and footwear on running mechanics.
AB  - BACKGROUND: Running shoes are designed to accommodate various arch types to
      reduce the risk of lower extremity injuries sustained during running. Yet little
      is known about the biomechanical changes of running in the recommended footwear
      that may allow for a reduction in injuries. PURPOSE: To evaluate the effects of
      motion control and cushion trainer shoes on running mechanics in low- and high
      arched runners. STUDY DESIGN: Controlled laboratory study. METHODS: Twenty high
      arched and 20 low-arched recreational runners (>10 miles per week) were recruited
      for the study. Three-dimensional kinematic and kinetics were collected as
      subjects ran at 3.5 ms(-1) +/- 5% along a 25-m runway. The motion control shoe
      evaluated was the New Balance 1122, and the cushioning shoe evaluated was the New
      Balance 1022. Repeated-measures analyses of variance were used to determine if
      low- and high-arched runners responded differently to motion control and cushion
      trainer shoes. RESULTS: A significant interaction was observed in the
      instantaneous loading rate such that the low-arched runners had a lower
      instantaneous loading rate in the motion control condition, and the high-arched
      runners had a lower instantaneous loading rate in the cushion trainer condition.
      Significant main effects for shoe were observed for peak positive tibial
      acceleration, peak-to-peak tibial acceleration, mean loading rate, peak eversion,
      and eversion excursion. CONCLUSION: These results suggest that motion control
      shoes control rearfoot motion better than do cushion trainer shoes. In addition,
      cushion trainer shoes attenuate shock better than motion control shoes do.
      However, with the exception of instantaneous loading rate, these benefits do not
      differ between arch type. CLINICAL RELEVANCE: Running footwear recommendations
      should be based on an individual's running mechanics. If a mechanical analysis is
      not available, footwear recommendations can be based empirically on the
      individual's arch type.

PMID- 16902232
TI  - Outcomes of stress fractures of the talus.
AB  - BACKGROUND: Stress fractures of the talus are rare, and only a few small studies
      have been published. In the absence of follow-up studies, the outcomes of these
      injuries are unknown. HYPOTHESIS: Traumatic fractures of the talus frequently
      heal poorly, and stress fracture healing might remain inadequate. The purpose of
      this study was to determine the outcome of stress fractures of the talus treated
      in the authors' institution with reduced exercise and nonweightbearing. STUDY
      DESIGN: Case series (prognosis); Level of evidence, 4. METHODS: Patients with a
      diagnosed stress fracture in the talus by magnetic resonance imaging between
      April 1997 and March 2005 were recalled for a follow-up inspection by an
      orthopaedic surgeon, magnetic resonance imaging, and plain radiographs to
      determine the outcome of the injury. RESULTS: One of the 9 patients in our sample
      declined the invitation, leaving 8 patients with 9 stress fractures in the talus
      who participated in the follow-up examination. Five patients displayed
      subchondral degeneration and edema near the original injury area in the follow-up
      magnetic resonance imaging. In 2 patients, the degeneration was also visible on
      the plain radiographs. Three patients had mild and 2 moderate symptoms after the
      mean follow-up time of 45 months (range, 12-74 months). No serious complications
      in the healing process were seen. CONCLUSION: Stress fractures of the talus do
      not seem to seriously damage the foot. In a middle-term follow-up, however, minor
      to moderate symptoms and radiological degeneration of the injured area prevailed
      in roughly half of the patients.

PMID- 16902233
TI  - Medial ulnar collateral ligament reconstruction of the elbow in throwing
      athletes.
AB  - BACKGROUND: Medial ulnar collateral ligament insufficiency of the elbow can be a
      devastating injury in the throwing athlete. Reconstruction of the medial ulnar
      collateral ligament was initially described by Jobe and associates; good clinical
      results have been described after this procedure. The authors' experience with
      this technique raised several concerns, and thus the "docking" procedure was
      developed as an alternative method for medial ulnar collateral ligament
      reconstruction of the elbow. The early results of the docking technique were
      good. The authors wish to investigate the intermediate-term clinical results of
      this method in a large group of athletes. HYPOTHESIS: The docking technique can
      return overhead-throwing athletes to sport with minimal perioperative morbidity.
      STUDY DESIGN: Case series; Level of evidence, 4. METHODS: During a 3-year period,
      100 consecutive overhead-throwing athletes were treated with surgical
      reconstruction using the docking technique. The inclusion criteria were as
      follows: (1) a history of medial elbow pain that prevented throwing, (2) a
      preoperative standard noncontrast magnetic resonance image demonstrating medial
      ulnar collateral ligament injury, (3) clinically apparent medial ulnar collateral
      ligament insufficiency, and (4) an overhead-throwing athlete. At the time of
      surgery, all patients underwent routine arthroscopic assessment. The ulnar nerve
      was transposed in 22 cases. The mean follow-up was 36 months (range, 24-60
      months). RESULTS: Ninety of 100 (90%) patients were able to compete at the same
      or a higher level than before medial ulnar collateral ligament injury for more
      than 12 months as noted at the follow-up interval; 7 patients were able to
      compete at a lower level. Only 3 patients suffered postoperative complications.
      CONCLUSION: The docking technique reliably returns athletes to competitive
      throwing with a low perioperative morbidity.

PMID- 16902234
TI  - Long-term results of arthroscopic Bankart repair with a bioabsorbable tack.
AB  - BACKGROUND: Short-term to midterm data are available on arthroscopic shoulder
      stabilization using bioabsorbable tacks or suture anchors. It remains unknown
      whether these techniques can equal the success of open Bankart repair in the long
      term. PURPOSE: To assess the long-term outcome of arthroscopic Bankart repair
      using bioabsorbable tacks in patients with traumatic anterior shoulder
      instability with a minimum follow-up of 7 years. STUDY DESIGN: Case series; Level
      of evidence, 4. METHODS: Treatment outcomes were determined prospectively
      according to the Rowe score and retrospectively according to the Constant and
      American Shoulder and Elbow Surgeons scores. Included in this study were 18
      consecutive patients with a mean age of 26.8 years (range, 16-62 years) who
      underwent arthroscopic Bankart repair using bioabsorbable tacks for traumatic
      anterior shoulder instability. The study group consisted of 14 male and 4 female
      patients. The mean follow-up was 8.7 years (range, 7.0-9.8 years). RESULTS: One
      patient had recurrent dislocations requiring further surgery, for an overall
      failure rate of 5.6%. An additional patient had 1 traumatic subluxation episode
      within the first postoperative year that did not recur. According to the Rowe
      score, which increased to 90.3 (17.8) from 32.8 (8.3) points preoperatively, 15
      patients (83.3%) achieved a good or excellent result. The mean Constant score was
      91.3 (SD, 6.9) points, and the mean American Shoulder and Elbow Surgeons score
      was 92.1 (SD, 6.9) points postoperatively. A return to the preinjury level of
      sports competition was reported by 64% of patients. No signs of synovitis
      occurred in any patient postoperatively. CONCLUSION: Arthroscopic Bankart repair
      for the treatment of recurrent traumatic anterior shoulder instability repair
      using bioabsorbable tacks offers reliable results with respect to failure rate,
      range of motion, and shoulder function during a minimum follow-up of 7.0 years.
      In contrast to previous reports on arthroscopic Bankart repair, results did not
      deteriorate during follow-up.

PMID- 16902235
TI  - Social control of health behavior: associations with conscientiousness and
      neuroticism.
AB  - Despite considerable research demonstrating associations of conscientiousness and
      neuroticism with health-related behavior, our understanding of how and why these
      traits are related to lifestyle is limited. This study examined the social
      regulation of health behavior in a probability sample of 509 household residents
      who completed a Random Digit Dial (RDD) telephone survey. Results suggest that
      the social regulation of health behavior experienced by highly conscientious
      individuals has more to do with their own internalized notions of responsibility
      and obligation to others than to specific actions by others aimed at influencing
      their health habits. In contrast, individuals with higher neuroticism experience
      more overt attempts by others to influence their health habits but have more
      negative affective and behavioral responses to these social influence attempts.
      Findings suggest that elucidating the distinct social influence processes that
      operate for conscientiousness and neuroticism may further understanding of how
      these traits are related to health behaviors and status.

PMID- 16902236
TI  - Responding to deviance: target exclusion and differential devaluation.
AB  - Two studies explored responses to ingroup deviance. Group-defining opinions of
      prowar Republicans (Study 1) and prolife Christians (Study 2) were challenged by
      either an ingroup or outgroup deviate. Participants evaluated the deviate and
      structured the boundaries of their ingroup in counterbalanced order. Of
      importance, boundary structuring allowed participants to exclude deviates from
      the ingroup. Consistent with previous research, ingroup deviates were devalued
      relative to out-group deviates, but only when target evaluation was participants'
      first response option. Participants excluded deviates from the boundaries of
      their ingroup irrespective of measure order, and doing so eliminated differential
      devaluation when exclusion was participants' first response option. Exclusion
      decreased liking for outgroup deviates in Study 1 and increased liking for
      ingroup deviates in Study 2. The findings suggest that devaluation is an attempt
      to exclude deviates from the ingroup and that doing so reduces the threat
      otherwise experienced.

PMID- 16902237
TI  - Music and aggression: the impact of sexual-aggressive song lyrics on aggression
      related thoughts, emotions, and behavior toward the same and the opposite sex.
AB  - Three studies examined the impact of sexual-aggressive song lyrics on aggressive
      thoughts, emotions, and behavior toward the same and the opposite sex. In Study
      1, the authors directly manipulated whether male or female participants listened
      to misogynous or neutral song lyrics and measured actual aggressive behavior.
      Male participants who were exposed to misogynous song lyrics administered more
      hot chili sauce to a female than to a male confederate. Study 2 shed some light
      on the underlying psychological processes: Male participants who heard misogynous
      song lyrics recalled more negative attributes of women and reported more feelings
      of vengeance than when they heard neutral song lyrics. In addition, men-hating
      song lyrics had a similar effect on aggression-related responses of female
      participants toward men. Finally, Study 3 replicated the findings of the previous
      two studies with an alternative measure of aggressive behavior as well as a more
      subtle measure of aggressive cognitions. The results are discussed in the
      framework of the General Aggression Model.

PMID- 16902238
TI  - When do ego threats lead to self-regulation failure? Negative consequences of
      defensive high self-esteem.
AB  - High self-esteem (HSE) is increasingly recognized as heterogeneous. By measuring
      subtypes of HSE, the present research reevaluates the finding that HSE
      individuals show poor self-regulation following ego threat (Baumeister,
      Heatherton, & Tice, 1993). In Experiment 1, participants with HSE showed poor
      self-regulation after ego threat only if they also were defensive (high in self
      presentation bias). In Experiment 2, two measures--self-presentation bias and
      implicit self-esteem--were used to subtype HSE individuals as defensive. Both
      operationalizations of defensive HSE predicted poor self-regulation after ego
      threat. The results indicate that (a) only defensive HSE individuals are prone to
      self-regulation failure following ego threat and (b) measures of self
      presentation bias and implicit self-esteem can both be used to detect
      defensiveness.

PMID- 16902239
TI  - Ego-involvement and the difficulty law of motivation: effects on performance
      related cardiovascular response.
AB  - Two experiments found that effort-related cardiovascular reactivity under ego
      involvement follows the principles of motivational intensity theory. Experiment 1
      manipulated ego-involvement and the difficulty of a memory task. Under high ego
      involvement, cardiovascular reactivity during task performance increased with
      fixed task difficulty; an unfixed performance standard elicited the same high
      reactivity as a fixed high standard. Experiment 2 manipulated ego-involvement and
      administered a memory task with unfixed versus extremely high performance
      standards. High ego-involvement increased cardiovascular reactivity only when the
      performance standard was unfixed but not when success was obviously impossible.
      Both studies found associations between cardiovascular reactivity and achievement
      and controlled for emotional states. The findings clarify previous research and
      theorizing about ego-involvement and motivation.

PMID- 16902240
TI  - Crossed categorization in common ingroup contexts.
AB  - In three experiments, the authors tested the hypothesis that a common ingroup
      context would moderate evaluations of crossed category targets. In Experiment 1,
      the typical additive pattern of evaluation across artificial crossed category
      groups became a social inclusion pattern in a common ingroup context. In
      Experiment 2, the authors manipulated the importance of real crossed category
      targets. When the crossed groups were of low importance, the effects of imposing
      a common ingroup replicated those observed in Experiment 1. For important crossed
      groups, however, the additive pattern remained. In Experiment 3, the authors
      measured perceived importance of the crossed groups to social identity prior to
      introducing a common ingroup context. The effects of a common categorization on
      evaluations were again moderated by perceived importance. These findings are
      discussed in the context of integrating crossed categorization and common ingroup
      identity models of multiple categorization.

PMID- 16902241
TI  - Are prosocials unique in their egalitarianism? The pursuit of equality in
      outcomes among individualists.
AB  - The present research aims to elucidate to what extent the motive to ensure
      equality in outcomes is general and to what extent it interacts with other
      important motives such as maximizing own or collective gains. Because individuals
      may have different considerations and motivations in decision-making situations,
      it is likely that people with a different social value orientation will respond
      differently to an unequal distribution of outcomes. Contrary to expectations, not
      only prosocials care about equality in outcomes. In Study 1, the authors found
      that individualists choose to forego personal gains, despite obvious selfish
      reasons to cooperate, when outcomes were distributed unequally. In a second
      experiment, this finding was replicated and shows that individualists, just as
      prosocials, demand equality in outcomes in interdependent situations. The studies
      suggest that typifying individualists as solely being concerned about enhancing
      personal outcomes is too limited and that fairness norms may trump social value
      orientation.

PMID- 16902242
TI  - Anger and guilt about ingroup advantage explain the willingness for political
      action.
AB  - Three studies examined non-Aboriginal Australians' guilt and anger about their
      ingroup's advantage over structurally disadvantaged Aborigines. Study 1 showed
      that participants who perceived their ingroup as relatively advantaged perceived
      this inequality as unfair and felt guilt and anger about it. Anger, and to a
      lesser degree guilt, predicted the willingness to engage in political action
      regarding ingroup advantage. Study 2 showed both guilt and anger to be relatively
      self-focused because both were associated with appraising the ingroup's (rather
      than the government's) discrimination as responsible for ingroup advantage. Study
      3 examined on participants especially willing to engage in political action to
      bring about systemic compensation to Aborigines. Anger about ingroup advantage
      was a potent predictor. Although guilt was associated with the abstract goal of
      systemic compensation, guilt did not explain willingness for political action.
      Results underline the importance of examining specific group-based emotions in
      intergroup relations.

PMID- 16902243
TI  - Social achievement goals: the nature and consequences of different orientations
      toward social competence.
AB  - The proposition that achievement goals are applicable to the social domain was
      examined in four studies. Study 1 established that different orientations toward
      developing or demonstrating social competence can be seen in individuals'
      responses to open-ended questions about their social goals and social competence.
      Studies 2 through 4 evaluated a new survey measure of social achievement goals.
      Exploratory and confirmatory factor analyses confirmed the hypothesized model of
      social achievement goals. Convergent and discriminant validity for the new
      measure of social achievement goals was established. In line with hypotheses, a
      social development goal was associated with adjustment and a social demonstration
      avoid goal was associated with maladjustment both concurrently and
      longitudinally. A social development goal also was positively related to
      instructor ratings of students' social adjustment in small classroom settings. A
      social demonstration-approach goal was most often unrelated to adjustment. The
      importance of social achievement goals for a comprehensive understanding of
      social motivation and adjustment is discussed.

PMID- 16902244
TI  - Ambivalence toward the body: death, neuroticism, and the flight from physical
      sensation.
AB  - Based on terror management theory, the authors suggest that ambivalent reactions
      to the human body are partially rooted in the association of the physical body
      with inescapable death and that individuals high in neuroticism are particularly
      vulnerable to such difficulties. Three experiments demonstrated that priming
      thoughts about one's death leads individuals high in neuroticism to flee from
      physical sensations, including pleasurable ones. In response to mortality
      salience, highly neurotic individuals spent less time submerging their arm in ice
      cold water and using an electric foot massager but did not avoid stimulation in
      nontactile modalities (i.e., listening to music). The discussion highlights the
      role of existentially motivated self-repression in inhibitions surrounding the
      body.

PMID- 16902245
TI  - Identification of small-molecule inhibitors of protein kinase B (PKB/AKT) in an
      AlphaScreenTM high-throughput screen.
AB  - Protein kinase B (PKB/AKT) has been identified as a promising cancer drug target
      downstream of PI3 kinase. To find novel inhibitors of PKB/AKT kinase activity for
      progression as anticancer agents, the authors have used a high-throughput screen
      based on AlphaScreentrade mark technology. A known kinase inhibitor, the
      isoquinoline H8, was used as a positive control with mean inhibition in the
      screen of 43.4% +/- 13.1%. The performance of the screen was highly acceptable
      with Z' and Z factors of 0.83 +/- 0.07 and 0.75 +/- 0.04, respectively. A number
      of confirmed hits ( approximately 0.1% hit rate) were identified from 63,500
      compounds screened. Five compounds have previously been described as PKB
      inhibitors, demonstrating the ability of the assay to find authentic inhibitors
      of the enzyme. Five hits had the potential to interfere with the assay signal and
      were deemed to be false positives. Two compounds were nonspecific inhibitors of
      PKB as enzyme inhibition in a filter-based assay was markedly reduced in the
      presence of 0.01% Triton X100. The authors now include an interference assay
      during hit confirmation procedures and check compound activity in the presence of
      Triton X100 in an attempt to eliminate nonspecific aggregators at an early stage.

PMID- 16902246
TI  - Thematic review series: systems biology approaches to metabolic and
      cardiovascular disorders. Lipidomics: a global approach to lipid analysis in
      biological systems.
AB  - Lipids are water-insoluble molecules that have a wide variety of functions within
      cells, including: 1) maintenance of electrochemical gradients; 2) subcellular
      partitioning; 3) first- and second-messenger cell signaling; 4) energy storage;
      and 5) protein trafficking and membrane anchoring. The physiological importance
      of lipids is illustrated by the numerous diseases to which lipid abnormalities
      contribute, including atherosclerosis, diabetes, obesity, and Alzheimer's
      disease. Lipidomics, a branch of metabolomics, is a systems-based study of all
      lipids, the molecules with which they interact, and their function within the
      cell. Recent advances in soft-ionization mass spectrometry, combined with
      established separation techniques, have allowed the rapid and sensitive detection
      of a variety of lipid species with minimal sample preparation. A "lipid profile"
      from a crude lipid extract is a mass spectrum of the composition and abundance of
      the lipids it contains, which can be used to monitor changes over time and in
      response to particular stimuli. Lipidomics, integrated with genomics, proteomics,
      and metabolomics, will contribute toward understanding how lipids function in a
      biological system and will provide a powerful tool for elucidating the mechanism
      of lipid-based disease, for biomarker screening, and for monitoring pharmacologic
      therapy.

PMID- 16902247
TI  - ABCA1 and ABCG1 or ABCG4 act sequentially to remove cellular cholesterol and
      generate cholesterol-rich HDL.
AB  - Recent developments in lipid metabolism have shown the importance of ATP binding
      cassette transporters (ABCs) in controlling cellular and total body lipid
      homeostasis. ABCA1 mediates the transport of cholesterol and phospholipids from
      cells to lipid-poor apolipoprotein A-I (apoA-I), whereas ABCG1 and ABCG4 mediate
      the transport of cholesterol from cells to lipidated lipoproteins. ABCA1, ABCG1,
      and ABCG4 are all expressed in cholesterol-loaded macrophages, and macrophages
      from ABCA1 and ABCG1 knockout mice accumulate cholesteryl esters. Here, we show
      that the lipidated particles generated by incubating cells overexpressing ABCA1
      with apoA-I are efficient acceptors for cholesterol released from cells
      overexpressing either ABCG1 or ABCG4. The cholesterol released to the particles
      was derived from a cholesterol oxidase-accessible plasma membrane pool in both
      ABCG1 and ABCG4 cells, which is the same pool of cholesterol shown previously to
      be removed by high density lipoproteins. ABCA1 cells incubated with apoA-I
      generated two major populations of cholesterol- and phospholipid-rich lipoprotein
      particles that were converted by ABCG1 or ABCG4 cells to one major particle
      population that was highly enriched in cholesterol. These results suggest that
      ABCG1 and ABCG4 act in concert with ABCA1 to maximize the removal of excess
      cholesterol from cells and to generate cholesterol-rich lipoprotein particles.

PMID- 16902251
TI  - One-appointment correction of a scissor bite with 2D lingual brackets and fiber
      reinforced composites.

PMID- 16902252
TI  - Surgical stents for accurate miniscrew insertion.

PMID- 16902253
TI  - The bite-jumping screw for modified twin-block treatment.

PMID- 16902254
TI  - Overlay mechanics with the Tip-Edge PLUS bracket, Part 2: Class II and III
      nonextraction treatment.

PMID- 16902255
TI  - Bisphosphonates in orthodontics.

PMID- 16902256
TI  - Acrylic occlusal rim.

PMID- 16902257
TI  - The readers' corner. What percentage of your patients use insurance to pay for
      part or all of their orthodontic treatment?

PMID- 16902258
TI  - The readers' corner. List the patient education materials that are used in your
      office.

PMID- 16902259
TI  - Bisphosphonates and orthodontics: Clinical implications.

PMID- 16902260
TI  - Association between serum ferritin and circulating oxidized low-density
      lipoprotein levels in patients with type 2 diabetes.
AB  - The oxidative modification of low-density lipoproteins (LDL) plays a central role
      in the initiation and acceleration of atherosclerosis. Iron plays a part in the
      formation of highly toxic free radicals such as hydroxide and superoxide anions,
      which can induce lipid peroxidation. We investigated whether serum iron status
      was associated with circulating oxidized LDL (oxLDL) levels in type 2 diabetic
      patients, in whom oxidative stress and susceptibility to lipid oxidation were
      supposedly increased. Serum ferritin levels were significantly correlated with
      plasma oxLDL concentrations in both male and female patients (p<0.02 and p<0.05,
      respectively). No correlation was detected between ferritin and LDL-cholesterol
      (LDL-C) concentrations despite the close correlation between LDL-C and oxLDL
      concentrations (p<0.0001). Stepwise regression analysis showed that ferritin
      concentration was an independent positive determinant of oxLDL level, in addition
      to triglyceride concentration, body mass index and sex. This is the first report
      to show that serum ferritin is associated with circulating oxLDL levels in
      patients with type 2 diabetes. Further work is required to establish a causative
      link between iron excess and the development of diabetic vascular complications.

PMID- 16902261
TI  - Intrasellar remote metastasis from adenoid cystic carcinoma of parotid gland:
      case report.
AB  - Adenoid cystic carcinoma is a tumor of exocrine glands originating primarily from
      the minor and major salivary glands, lacrimal gland, bronchus, breast, and
      intestinal and genital tracts. Intracranial remote metastasis from adenoid cystic
      carcinoma in salivary gland is quite rare. The authors encountered a case of
      intrasellar remote metastasis from an adenoid cystic carcinoma of parotid gland
      origin, presenting with hyponatremia secondary to the syndrome of inappropriate
      secretion of antidiuretic hormone (SIADH). To our knowledge, this is the first
      reported case of metastasis from an adenoid cystic carcinoma to intrasellar area.
      A 78-year-old woman had an adenoid cystic carcinoma in the left parotid gland,
      which was resected surgically followed by local radiation therapy of 60 Gy. After
      4 years, the patient presented with general malaise, followed by disturbed
      consciousness caused by hyponatremia. The clinical data showed severe
      hyponatremia induced by SIADH. An intrasellar heterogenous mass lesion
      compressing the optic chiasm was resected subtotally via an endonasal
      transsphenoidal approach. Histopathological examination of the tumor specimens
      revealed adenoid cystic carcinoma, which had identical histological findings as
      those of the painful superficial cervical lymph nodes resected in the same
      operation. Tumors such as the present case are easily confused with pituitary
      adenoma or craniopharyngioma. Although rare, metastasis from tumors including
      those of salivary gland origin should be considered in the differential diagnosis
      of unusual pituitary tumors.

PMID- 16902262
TI  - Subclinical hypothyroidism is associated with early insulin resistance in Kuwaiti
      women.
AB  - Subclinical hypothyroidism (SH), defined as an asymptomatic state characterized
      by normal serum concentrations of free thyroxine and elevated serum
      concentrations of TSH. The aim of this study is to investigate the complex
      interplay between insulin resistance and low grade chronic inflammation in
      Kuwaiti women with subclinical hypothyroidism. Thirty four women with subclinical
      hypothyroidism (SH) and 20 healthy women as controls matched to the patient group
      for sex, age and body mass index (BMI), were enrolled in this prospective study.
      TSH, FT4, C reactive protein, glucose, insulin, Homeostasis Model assessment
      (HOMA), total cholesterol (TC), triglycerides (TG), low-density lipoprotein
      cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) were estimated.
      Total cholesterol and LDL-C were significantly higher in patients with SCH as
      compared with control subjects, however triglyceride and HDL-C were not
      statistically different. CRP was not statistically different between the SCH
      patients and control group (3.64 +/- 0.94 Vs 3.18 +/- 0.71 P>0.05). Insulin
      levels were significantly higher in the SCH group comparable to the control (12.5
      +/- 2.67 Vs 10.80 +/- 2.01 p<0.05), however HOMA-IR was not statistically
      different (2.85 +/- 0.64 Vs 2.54 +/- 0.64 P>0.05). Patients with subclinical
      hypothyroidism exhibited elevated atherogenic parameters (hyperinsulinemia, total
      cholesterol, LDL-C). Therefore screening and treatment for subclinical
      hypothyroidism may be warranted due to its adverse effects on lipid metabolism.

PMID- 16902263
TI  - Molecular analysis of the CLCNKB gene in Japanese patients with classic Bartter
      syndrome.
AB  - Deletions or mutations in the gene encoding the basolateral chloride channel CLC
      Kb (CLCNKB) cause classic Bartter syndrome (MIM 602023), which is characterized
      by hypokalemic metabolic alkalosis, hyperreninemic hyperaldosteronism and
      hypercalciura. These patients are usually diagnosed during infancy or childhood
      due to failure to thrive and growth retardation. The purpose of this study was to
      investigate the underlying mutations in Japanese patients with classic Bartter
      syndrome. Seven Japanese patients from seven different families diagnosed as
      having classic Bartter syndrome were studied. Analysis of CLCNKB demonstrated a
      large deletion in two patients, a partial deletion in one patient and two
      mutations (DeltaL130 in exon 4 and W610X in exon 16) in the remaining four
      patients. DeltaL130 is a novel mutation, but W610X was previously reported in
      three unrelated Japanese patients. Six out of the seven patients were diagnosed
      due to typical characteristics of classic Bartter syndrome such as failure to
      thrive and poor weight gain however, one patient was asymptomatic with mild
      hypokalemia. In conclusion, we identified a novel mutation of the CLCNKB gene,
      DeltaL130. We did not determine whether the W610X mutation in our patients was
      from a common ancestor or if this mutation is frequent in Japan.

PMID- 16902264
TI  - Long-term effects of recombinant human insulin-like growth factor I treatment on
      glucose and lipid metabolism and the growth of a patient with congenital
      generalized lipodystrophy.
AB  - Congenital generalized lipodystrophy (CGL) is a disease characterized by
      generalized lack of body fat, insulin resistance, hypertriglyceridemia, and fatty
      liver. We studied the long-term effects of recombinant human insulin-like growth
      factor I (rhIGF-I) treatment on glucose and lipid metabolism and the growth in a
      patient with CGL. During rhIGF-I treatment, the serum triglyceride level was
      maintained almost within the normal range, and the plasma glycosylated hemoglobin
      A1c (HbA1c) levels were maintained under 8.0% (5.8%-7.9%). Thus, rhIGF-I
      treatment was effective in lowering glucose and triglyceride levels over the long
      term in a CGL patient. However, it was difficult to suppress the patient's
      voracious appetite. Although serum total IGF-I levels were extremely high (1000
      1700 ng/ml), growth was not accelerated after the start of rhIGF-I treatment,
      likely because of normal IGF binding protein 3 (IGFBP-3) levels. During rhIGF-I
      treatment, the patient developed a recurrence of mild hypertrophic cardiomyopathy
      and a mild elevation of intraocular pressure.

PMID- 16902265
TI  - Risk factors for heatstroke among Japanese forestry workers.
AB  - We examined the risk factors for heatstroke among forestry workers in Japan
      during the summer. We distributed a questionnaire to 124 forestry workers to
      determine heatstroke symptoms, degree of sweating and hydration, as well as
      perceived hotness and amount of sunlight at work sites. Forty of the workers
      (32.3%) reported experiencing heatstroke symptoms. Thirteen and 21 of them
      reported such symptoms during July and August, respectively. Eleven workers
      experienced heatstroke at around 14:00; 5 and 4 developed symptoms at around
      11:00 and 10:00, respectively. Groups with and without heatstroke symptoms
      significantly differed in terms of perceived hotness (p<0.05), sunlight (p<0.05),
      degree of sweating (p<0.01) and frequency of hydration (p<0.05) while working.
      Heatstroke symptoms developed in 60.6% of workers aged up to 50 yr, but in only
      22.0% of those over the age of 51 (p<0.01). Multiple regression analysis selected
      the following key variables associated with the development of heatstroke
      symptoms (R(2)=0.236 and p=0.006): frequency of urination, hotness, BMI and years
      of forestry work (standard coefficients: +0.229, +0.194, +0.280 and -0.162,
      respectively). The results of the present study showed that one third of forestry
      workers developed some symptoms of early heatstroke during summer forestry work.
      Furthermore, the results indicate that a short duration of forestry service was
      one of the risk factors contributing to the onset of heatstroke, in addition to
      heat stress, loss of body water and electrolytes, and obesity.

PMID- 16902266
TI  - Perceived sleepiness of non-shift working men in two different types of work
      organization.
AB  - Increased sleepiness at work is increasingly being focused on as a safety and
      health issue. However, research on workers' sleepiness is very limited in scope
      and the characteristics of work organization, including the impact of job stress,
      have not been fully addressed. A questionnaire survey was conducted to
      investigate the prevalence of daytime sleepiness and its associated factors among
      non-shift working men at two manufacturing businesses: Company A, having a rapid
      rate of development and growth, with 564 workers (19-61 yr old, mean age: 32.7,
      response rate: 81.4%); and Company B, long established, possessing a huge
      production facility, with 1,654 workers (20-63 yr old, mean age: 37.1, response
      rate: 78.2%). The prevalence of daytime sleepiness was 11.3% in company A and
      16.8% in company B. Multivariate logistic regression analysis revealed that, in
      company A, perceived sleepiness was associated with long sleep duration on non
      working days and high cognitive demands and, in company B, with insufficient
      daily sleep, single, and depression. Psychosomatic exhaustion resulting from jobs
      requiring high adaptivity due to rapid frequency of operational change as in
      company A may have the potential to become an important factor in perceived
      sleepiness. However, in a comparatively stable work organization, as in company
      B, increased sleepiness may be mainly linked to factors outside work. It is
      suggested that not only lifestyle and sleep habits, but also the characteristics
      and dynamics of a work organization should be a focus of attention when planning
      measures to prevent sleepiness at work.

PMID- 16902267
TI  - Controlled trial of worksite health education through face-to-face counseling vs.
      e-mail on drinking behavior modification.
AB  - This study examined the effectiveness of a traditional face-to-face health
      education and e-mail health education on alcohol usage among male workers in
      comparison with a control group. Male workers at a manufacturing plant (N=36) who
      had abnormal serum gamma-GTP were stratified by age and job types, then
      randomized into three groups: face-to-face education, e-mail education, and the
      control. The subjects were assessed on their knowledge about and attitude towards
      drinking, reported alcohol consumption, and serum gamma-GTP before the start of
      education and 2 months later after comparison of the education. Paired t-test and
      repeated ANOVA were conducted to test the significance of changes pre and post
      the intervention and across groups. In the face-to-face group, knowledge
      (p=0.001), attitude (p=0.026), alcohol consumption (p=0.003) and serum gamma-GTP
      showed significant improvement. In the e-mail group, only alcohol consumption
      showed marginal improvement (p=0.077). In the control group, no variables
      remarkably changed. These results indicate that the face-to-face health education
      was more effective than the e-mail program. We discuss why the face-to-face
      approach was superior to the e-mail approach in this study by referring to self
      monitoring, goal setting processes and timely feedback. We concluded that further
      studies are warranted to identify the effect of health education using e-mails
      and other network tools in consideration of the above three factors.

PMID- 16902268
TI  - Increased susceptibility to varicella-zoster virus among Israeli physicians and
      nurses born in the Middle-East region.
AB  - Nosocomial transmission of varicella-zoster virus (VZV) is recognized as a
      significant cause of morbidity in health care workers as well as in high-risk
      patients. The current study aimed to investigate the presence of VZV antibodies
      among physicians and nurses, to assess the variables affecting it, and to compare
      it with previous international studies. Data were obtained by a questionnaire
      regarding sociodemographic and occupational characteristics and by determination
      of serum antibodies to varicella-zoster. The seroprevalence of varicella-zoster
      among the 335 study participants was 94.8% (95%CI: 91.9%-96.9%), with no
      significant difference between nurses (94%) and physicians (97%). Decreased risk
      for the virus was observed in workers who immigrated to Israel from the Asia or
      Africa (OR=0.15; 95% CI: 0.04-0.51). Reduced immunity among these workers
      remained significant in a multivariate model, which also included age, gender,
      years of education, number of siblings, and crowding at childhood. Our data
      suggest that in spite of the high immunity among Israeli physicians and nurses in
      general, the implementation of small-scale vaccination programs aimed at workers
      from warmer and tropical areas, should be seriously considered.

PMID- 16902269
TI  - Prolactin levels in workers exposed to chemical, physical and psycho-social urban
      stressors.
AB  - The aim of this study was to evaluate whether traffic police officers exposed to
      chemical, physical and psycho-social stressors, are at risk for alterations in
      plasma levels of prolactin (PRL) compared to a control group. Plasma PRL levels
      were evaluated in 92 male and 51 female, non-smoker, traffic police officers
      exposed to urban stressors and in 92 male and 51 female controls, matched by sex,
      age and working life (mean, SD and distribution), after excluding workers with
      the principal extra-occupational confounding factors. Mean PRL levels were
      significantly higher than controls in non-smoker, male and female traffic police
      officers (respectively, p=0.000 and p=0.013). The number of non-smoker, male and
      female traffic police officers with PRL values outside the upper normal limit for
      our laboratory was higher than, but not significantly different from controls.
      Mean PRL levels were not significantly higher than controls in smoker, male and
      female traffic police officers. The number of smoker, male and female traffic
      police officers with PRL values outside the normal limit for our laboratory was
      not significantly different from controls. The results suggest that exposure to
      urban chemical and physical stressors, interacting with psychosocial factors, may
      have an influence on PRL levels in traffic police officers. The level of plasma
      PRL might be a useful early biological marker for workers exposed to urban
      stressors.

PMID- 16902270
TI  - Aberrant promoter methylation of p16(INK4a) and O(6)-methylguanine-DNA
      methyltransferase genes in workers at a Chinese uranium mine.
AB  - To find the possible association of gene methylation of p16(INK4a) and O(6)
      Methylguanine-DNA Methyltransferase (O(6)-MGMT) with occupational exposure to
      radon, 91 male miners from a uranium mine in China were divided into 4 groups
      according to the cumulative doses of radon exposure from 2 to 425 WLM (working
      level months), and aberrant promoter methylation of p16(INK4a) and O(6)-MGMT
      genes in sputum samples was determined by a specific PCR assay. The results
      revealed that the methylated rates of 16(INK4a) gene (z=2.844, P=0.005) and O(6)
      MGMT gene (z=3.034, P=0.002), and the total methylated rate of these two genes
      (z=3.859, P=0.0001) increased significantly with the cumulative doses of radon
      among the miners. This methylation could be applied as a potential marker for the
      detection of early DNA damage induced by occupational radon exposure.

PMID- 16902271
TI  - Determinants of occupational fracture proneness: a case-control study in
      construction and railway workers.

PMID- 16902272
TI  - Acute pulmonary injury due to exposure to a high concentration of
      trichloroethylene vapor.

PMID- 16902273
TI  - Cervical HIVD probably related to long-term repetitive shock and neck flexion
      among dump-truck drivers.

PMID- 16902274
TI  - The relationship between coping with stress and employment in patients receiving
      maintenance hemodialysis.
AB  - The goal of this study was to assess the relationship between emotion- and task
      oriented coping (EOC/TOC) with stress and employment in patients undergoing
      maintenance hemodialysis. Individuals aged 18 to 64 yr who had uremia and had
      been undergoing hemodialysis regularly for at least three months were evaluated
      according to sociodemographic and clinical factors. Work status was defined using
      the most recent International Labour Organization definitions. Patients were
      requested to complete the following questionnaires: the Japanese version of the
      Coping Inventory for Stressful Situations, the Short Form-36 Health Survey, an
      item on itchiness, the Self-Efficacy on Health-Related Behavior Scale, the
      Japanese version of the Health Locus of Control Scale, the Social Support Scale,
      and the Japanese version of the Hospital Anxiety and Depression Scale. A total of
      317 individuals participated in this study. Among men, age, physical functioning,
      EOC, and depression differed significantly (p<0.05) depending on employment.
      Among women, marital status, household composition, EOC, depression, and anxiety
      differed significantly (p<0.05) depending on employment. TOC was not
      significantly associated with employment in either sex. Multiple logistic
      regression analyses, including possible confounders, indicated that when EOC
      increased by 10 points, the associated adjusted odds ratio of an unemployed or
      economically inactive status changed by 1.48 (95% confidence interval, 1.04-2.11;
      p=0.030) in men and by 1.88 (95% confidence interval, 1.02-3.46; p=0.042) in
      women. These results suggest that EOC is associated with employment in patients
      receiving maintenance hemodialysis.

PMID- 16902275
TI  - Using urine specific gravity to evaluate the hydration status of workers working
      in an ultra-low humidity environment.
AB  - In environments with ultra-low humidity, workers may have excessive body water
      loss due to evaporation through the skin, which can lead to dehydration. Before
      the development of clinical symptoms and signs, concentrated urine may be applied
      as an early indicator of dehydration. We used urine specific gravity (USG) as a
      biomarker to evaluate the hydration status of workers working in such an
      environment. We collected the urine samples from workers at a lithium battery
      plant during their annual health examination, and the relative humidity of some
      working areas called "dry rooms" in the plant was 1.5 +/- 1%. We recruited
      workers in those dry rooms as the exposure group (N=50) and defined the remaining
      workers, including administration office workers, as the comparison group
      (N=122). The prevalence of abnormally concentrated urine (USG>1.030) and related
      factors were compared between these two groups. While the exposure group were
      younger and had shorter employment durations compared to the comparison group
      (p<0.05), they had a higher prevalence of abnormally concentrated urine (p<0.01).
      After adjusting for age, gender, employment duration, and body surface area, we
      found that working in the dry rooms was associated with an odds ratio of 11.9
      (95% confidence interval: 2.5 to 56.9) of having abnormally concentrated urine.
      Therefore, USG is a good biomarker for evaluating the hydration status of workers
      working in ultra-low humidity environments, who need proper protection and
      adequate fluid supply to prevent excess water loss and its adverse health
      effects.

PMID- 16902276
TI  - Clustering of risk factors increases the incidence of echolucent carotid plaque
      in stroke patients.
AB  - BACKGROUND: The purpose of this study was to assess the influence of clusters of
      risk factors on the incidence of echolucent carotid plaque in stroke patients.
      METHODS: A retrospective analysis of 413 stroke patients who had undergone
      carotid ultrasonography was performed. High-resolution B-mode ultrasonography was
      used to evaluate the characteristics of carotid plaque. We investigated the
      relationships between the incidence of echolucent carotid plaque and clustering
      of risk factors (hypertension, diabetes mellitus and hyperlipidemia) and stroke
      subtypes and transient ischemic attack (TIA). RESULTS: Echolucent plaques were
      present in 10.5% of patients free of risk factors, in 18.8% with a single risk
      factor (NS), in 27.7% with two risk factors (p <0.01) and in 50.0% with three
      risk factors (p <0.001), and were significantly more common in patients with
      multiple risk factors (odds ratio 1.79; 95% CI, 1.05-3.06; p = 0.045). Echolucent
      plaques were observed in 41.2% of patients with atherothrombotic infarction, in
      17.6% with lacunar infarction, in 11.5% with cardioembolic stroke, and in 25.0%
      with TIA, and were significantly more common in patients with atherothrombotic
      infarction than in those with lacunar infarction or cardioembolic stroke
      (p<0.001), or in those with TIA (p <0.05). CONCLUSIONS: The clustering of risk
      factors increased the incidence of echolucent carotid plaque. Patients with
      multiple risk factors were at increased risk of echolucent plaque, and these had
      a significant relationship with atherothrombotic infarction compared with other
      stroke subtypes and TIA.

PMID- 16902277
TI  - The prevalence of autonomic symptoms in dementia and their association with
      physical activity, activities of daily living and quality of life.
AB  - BACKGROUND/AIMS: There is little published data regarding autonomic symptoms in
      dementia. This study aimed to examine the prevalence and severity of autonomic
      symptoms in patients with different subtypes of dementia in comparison with
      healthy controls, and their association with levels of physical activity,
      depression, quality of life and ability to carry out activities of daily living.
      METHODS: Prevalence and severity of autonomic symptoms in Parkinson's disease
      dementia (PDD, n = 46), dementia with Lewy bodies (DLB, n = 32), vascular
      dementia (VAD, n = 38), Alzheimer's disease (AD, n = 40) and healthy controls (n
      = 42) were assessed using a structured symptom scale. The associations between
      autonomic symptoms and physical activity, Bristol Activities of Daily Living
      Score, Geriatric and Cornell Depression Scores and quality of life (Medical
      Outcomes Study 36-Item Short Form Health Survey, SF-36) were examined by multiple
      linear regressions. RESULTS: Total autonomic symptom scores, urinary symptoms,
      constipation and postural dizziness were significantly higher in PDD, DLB and VAD
      patients than either controls or AD patients (all p < 0.05). Higher autonomic
      symptom scores were associated with poorer outcomes in all measures of physical
      activity, activities of daily living, depression and quality of life. CONCLUSION:
      The burden of autonomic symptoms is high in non-Alzheimer's dementias. The
      identification of such symptoms is of importance because of the detrimental
      effect of these symptoms upon physical activity, depression, activities of daily
      living and quality of life.

PMID- 16902278
TI  - Cognitive deficits in familial Alzheimer's disease associated with M239V mutation
      of presenilin 2.
AB  - The neuropsychological assessment of non-demented subjects with gene mutation of
      familial Alzheimer's disease (AD) provides a model for exploring the early
      cognitive features of the disease. We evaluated 1 patient and 6 non-demented
      subjects belonging to a family with AD with M239V mutation of the presenilin 2
      gene, aiming to verify the contribution of specific cognitive patterns to the
      characterization of familial AD. One patient, 3 non-demented subjects with M239V
      mutation and 3 subjects without mutation from the same family underwent
      neuropsychological testing. The patient's cognitive profile was characterized by
      anosognosia, visuospatial agnosia, apraxia and fluent aphasia. Of the 3 non
      demented subjects with mutation, 1 showed no deficits, another constructive
      apraxia and the third spatial perception and memory deficits. The 3 subjects
      without mutation showed normal abilities. The cognitive deficits of the non
      demented subjects with mutations indicate focal dysfunction of the posterior
      cortical areas, resembling the more extended parieto-occipito-temporal
      dysfunction of the demented patient. Such grading of visuospatial, praxis, and
      language impairments highlights a distinctive pattern related to the M239V
      mutation of the presenilin 2 gene.

PMID- 16902279
TI  - Rethinking the dementia diagnoses in a population-based study: what is
      Alzheimer's disease and what is vascular dementia?. A study from the kungsholmen
      project.
AB  - OBJECTIVE: To explore the hypothesis that older adults often are affected by more
      than one disease, making the differential diagnosis between Alzheimer's disease
      (AD) and vascular dementia (VaD) difficult. METHODS: Incident dementia cases (n =
      308) from a population-based longitudinal study of people 75+ years were
      investigated. The DSM-III-R criteria were used for the clinical diagnosis of
      dementia. Data on vascular disorders (hypertension, cerebrovascular and ischemic
      heart diseases, heart failure, atrial fibrillation, diabetes) as well as type of
      onset/course of dementia were used retrospectively to reclassify dementias.
      RESULTS: Only 47% of the AD cases were reclassified as pure AD without any
      vascular disorder. Among subjects with AD and with a vascular component,
      cerebrovascular disease was the most common (41%). Only 25% of VaD were
      reclassified as pure VaD. Further, 26% of the pure AD subjects developed a
      vascular disorder in the following 3 years. CONCLUSIONS: Both vascular and
      degenerative mechanisms may often contribute to the expression of dementia among
      the elderly. Most of the AD cases have vascular involvements, and pure dementia
      types in very old subjects constitute only a minority of dementia cases.

PMID- 16902280
TI  - Decreased theta event-related synchronization during working memory activation is
      associated with progressive mild cognitive impairment.
AB  - BACKGROUND: Among the different quantitative electroencephalographic markers,
      theta activity is known to reflect neural resources involved in memory processes
      and directed attention. Previous studies suggested that synchronization
      likelihood analysis in theta-band frequency might be a sensitive method to
      identify early alterations of neuronal networks in mild cognitive impairment
      (MCI). METHODS: We report here a longitudinal study of 24 MCI patients with theta
      event-related synchronization (ERS) analysis during the n-back working memory
      task and neuropsychological follow-up after 1 year. Statistical analysis included
      analysis of variance and logistic regression to assess the relationship between
      cognitive decline and theta ERS. RESULTS: Upon follow-up, 13 MCI patients showed
      progressive MCI and 11 remained stable. In both groups, the phasic increase in
      theta amplitude after stimulus presentation did not depend on working memory load
      and electrode sites. Progressive MCI cases displayed significantly lower theta
      ERS power over all electrode sites compared to stable MCI cases. Theta ERS was
      significantly related to the cognitive outcome explaining 15.5% of its
      variability. In terms of MCI classification, the best combination of sensitivity
      and specificity was 0.87 and 0.60, respectively, with an area under the
      corresponding receiver operating characteristic curve reaching 76%. CONCLUSIONS:
      The present data indicate that a decrease in the early phasic theta ERS power
      during working memory activation may predict cognitive decline in MCI. This
      phenomenon is not related to working memory load but may reflect the presence of
      early deficits in directed attention-related neural circuits in MCI.

PMID- 16902281
TI  - Treatment of delusions in Alzheimer's disease--response to pharmacotherapy.
AB  - Delusions are commonly encountered symptoms in patients with Alzheimer's disease
      and may lead to significant morbidity. The purpose of this article is to review
      all clinical trials to date focusing on the management of delusions in patients
      with Alzheimer's disease to determine the level of evidence for treatment. To
      achieve this objective, Medline was searched using the key words delusions,
      dementia, Alzheimer's disease and psychosis. Three main categories of treatment
      were identified: atypical antipsychotics, cholinesterase inhibitors, and other
      miscellaneous treatments. It was concluded that all forms of treatment were
      effective although the greatest burden of evidence existed for risperidone and
      donepezil. Side effects were noted in all forms of treatment and included
      somnolence and extrapyramidal effects for antipsychotic medications, whereas
      gastrointestinal effects were more prevalent in studies involving cholinesterase
      inhibitors. Further large scale, double-blind, randomized, controlled studies are
      required before a definitive conclusion can be reached. To our knowledge this is
      the only systematic review of this area.

PMID- 16902282
TI  - Do the telangiectases of hereditary hemorrhagic telangiectasia and the
      calcinosis, Raynaud's disease, sclerodactyly, telangiectasia variant of
      scleroderma have a common etiology?

PMID- 16902283
TI  - Expansion of IL-10-producing CD4+ and CD8+ T cells in fixed drug eruption.
AB  - BACKGROUND: A severe form of fixed drug eruption (FDE) clinically and
      histologically mimics toxic epidermal necrolysis (TEN) but, unlike TEN, resolves
      spontaneously upon withdrawal of the causative drug. OBJECTIVE AND METHODS: We
      reported a case of a severe FDE caused by mefenamic acid that spontaneously
      resolved without use of systemic corticosteroids. To clarify the phenotype of the
      T cells responsible for clinical resolution of FDE, we kinetically examined gamma
      interferon (IFN-gamma), interleukin (IL)-2, IL-4 and IL-10 production by
      peripheral blood T cells of the patient before and after oral challenge with the
      causative drug using flow cytometry. RESULTS: We found that the proportions of
      CD4+ and CD8+ T cells capable of producing IFN-gamma and IL-4 remained unchanged
      after challenge, while those of CD4+ and CD8+ T cells capable of producing IL-10
      dramatically increased after challenge. The frequency of CD8+ T cells capable of
      producing IL-2 decreased after challenge. CONCLUSION: These results suggest that
      expansion of IL-10-producing CD4+ and CD8+ T cells may be responsible for
      spontaneous resolution of a severe form of FDE.

PMID- 16902284
TI  - A clue for telangiectasis in systemic sclerosis: elevated serum soluble endoglin
      levels in patients with the limited cutaneous form of the disease.
AB  - BACKGROUND: The transforming growth factor-beta (TGF-beta) system plays a
      critical role both in systemic sclerosis (SSc) and hereditary hemorrhagic
      telangiectasia (HHT). Endoglin, known as a gene responsible for HHT, is a TGF
      beta receptor preferentially expressed on endothelial cells. The role of endoglin
      in SSc is potentially intriguing since limited cutaneous SSc (lcSSc) and HHT
      share several symptoms, including telangiectasia. OBJECTIVE: To determine serum
      levels of soluble endoglin (sEndoglin) and clinical associations in patients with
      SSc. METHODS: Serum sEndoglin levels were examined by ELISA in 70 patients with
      SSc, 20 patients with systemic lupus erythematosus and 20 healthy individuals.
      RESULTS: Serum sEndoglin levels were significantly elevated in patients with
      lcSSc compared with diffuse cutaneous SSc and systemic lupus erythematosus
      patients as well as normal controls. Patients with elevated sEndoglin levels had
      telangiectasia more frequently than those with normal sEndoglin levels.
      Furthermore, pulmonary artery pressure was positively correlated with sEndoglin
      levels in patients with lcSSc. CONCLUSION: Abnormal expression/function of
      endoglin may be linked to lcSSc-specific manifestations.

PMID- 16902285
TI  - Eosinophilic fasciitis 30 years after - what do we really know? Report of 11
      patients and review of the literature.
AB  - BACKGROUND: Eosinophilic fasciitis (EF) is a rare fibrosing disorder associated
      with peripheral eosinophilia and scleroderma-like induration of the distal
      extremities which affects substantially quality of life. Although the disease has
      been described 30 years ago, the etiology and pathomechanisms are still obscure,
      and consensus for therapy is lacking. Numerous case reports of patients with EF
      exist but series are scarce. PATIENTS AND METHODS: Eleven patients with EF from
      the Department of Dermatology, Kantonsspital Aarau, the University Hospital Basel
      and the Outpatient Clinic of Dermatology, Triemli Hospital Zurich, Switzerland,
      were retrospectively studied. RESULTS: In 4 patients the initial diagnosis was
      not recognized by the referring nondermatologists. The median age was 55 years,
      excluding the youngest patient ever diagnosed with EF (age = 1 year). All
      patients showed an induration of the skin, which led to painful contractures in
      the joints in 3 cases. All but 2 patients demonstrated edema. A slight
      predominance of the upper extremities was observed. Sclerodactyly was noticed in
      1 patient. Three patients reported an initial trauma at the affected site. Two
      patients were tested positive for borreliosis. One patient subsequently developed
      aplastic anemia and Hashimoto thyroiditis. Visceral or extracutaneous involvement
      was absent. Eight patients had a full or partial recovery under corticosteroids
      whereas in 2, improvement could be achieved only with cyclosporine, azathioprine
      or cyclophosphamide. CONCLUSIONS: The diagnosis of EF can be established by
      clinical, laboratory and histological findings. In general, corticosteroids are
      highly efficacious in EF and only a minority of patients need other
      immunosuppressive or cytostatic drugs.

PMID- 16902286
TI  - Work limitations and productivity loss are associated with health-related quality
      of life but not with clinical severity in patients with psoriasis.
AB  - BACKGROUND: According to current guidelines the cost of productivity loss should
      be considered in pharmacoeconomic analyses. The cost of health-related
      productivity loss in psoriasis patients is unknown. OBJECTIVE: To estimate the
      cost of productivity loss in psoriasis and its association with health-related
      quality of life and clinical disease severity. METHODS: Cross-sectional study,
      recruitment of adult participants through Internet advertisements. 201 (72.3%)
      out of 278 eligible participants completed the study. Health-related work
      productivity loss, quality of life and clinical severity of psoriasis were
      assessed by standardized instruments. RESULTS: Indirect costs of productivity
      loss clearly exceed the total direct cost. In contrast to objective clinical
      disease severity, health-related quality of life (measured by the Dermatology
      Life Quality Index) is an independent predictor of work productivity.
      CONCLUSIONS: There is good reason to believe that intervention can reduce health
      related productivity loss by improving patients' quality of life. Savings from
      increased work productivity might offset comparatively high acquisition costs of
      biological agents.

PMID- 16902287
TI  - Identification of lesional CD4+ CD25+ Foxp3+ regulatory T cells in Psoriasis.
AB  - BACKGROUND: Depletion of CD4+ CD25+ Foxp3+ naturally occurring regulatory T cells
      (T(reg)) induces autoimmune phenomena. These cells have not yet been fully
      characterized in the skin of psoriatic patients. OBJECTIVES: To prove that the
      Zenon immunofluorescent labeling technique is suitable for the demonstration of
      co-localization of T-cell markers and in particular to show the distribution of
      T(reg) in psoriatic skin. METHODS: In biopsies derived from normal and psoriatic
      skin, CD4+ CD25+, CD4+ CD45RO+, CD8+ CD25+, CD8+ CD45RO+ and CD4+ CD25+ Foxp3+
      cells in the dermis and in the epidermis were immunophenotyped, using a
      quantitative immunofluorescent labeling technique (Zenon), analyzed and compared
      using image analysis. RESULTS: The immunofluorescent labeling technique was shown
      to be an easy and reliable tool to demonstrate co-localization of T-cell markers.
      In psoriasis, all pathogenic T-cell subsets (CD4+ CD25+, CD4+ CD45RO+, CD8+ CD25+
      and CD8+ CD45RO+ cells) were significantly increased in the dermis and in the
      epidermis, as compared to normal skin (all p < 0.05). Using this labeling
      technique we were able to reveal CD4+ CD25+ Foxp3+ T(reg) in psoriatic dermis,
      but not in the dermis of normal skin (p < 0.0001). CONCLUSIONS: The Zenon
      immunofluorescence technique in combination with image analysis is suitable for
      the demonstration of co-localization of T-cell markers in tissue. Increased
      numbers of pathogenic T cells (CD4+ CD25+, CD4+ CD45RO+, CD8+ CD25+ and CD8+
      CD45RO+) were shown in the dermis and epidermis, whereas CD4+ CD25+ Foxp3+ T(reg)
      were identified in psoriatic skin with a predilection for the upper dermis.

PMID- 16902288
TI  - Rotation flap reconstruction for nasal tip defect after mohs surgery.
AB  - BACKGROUND: Skin cancer of the nasal tip is frequent, and reconstruction after
      Mohs surgery might be challenging. The rotation flap is a very commonly used flap
      for reconstructions on the vertex and the extremities but rarely on the nose. In
      textbooks rotation flaps in nose reconstruction are rarely mentioned. OBJECTIVE:
      We present a rotation flap from the caudal tip and the columella of the nose for
      defects of the lateral tip of the nose. METHODS: With graphics and photographs of
      case studies we explain the mechanism of placement and movement of the flap.
      RESULTS: The rotation flap is useful for reconstructions of medium-size defects
      of the distal lateral nose tip. CONCLUSION: The rotation flap can be used in the
      reconstruction of laterally placed nasal tip defects. As this flap is not
      mentioned in textbooks for nasal tip reconstruction, its value for this
      localization is probably underestimated.

PMID- 16902289
TI  - Dermatologists' views and opinions about photo(chemo)therapy and conventional
      systemic psoriasis therapies: results from a Belgian survey.
AB  - BACKGROUND: Experts' opinions about old and new psoriasis therapies are well
      documented. OBJECTIVES: To document the views and opinions of a large, diverse
      group of dermatologists about psoriasis treatment. PARTICIPANTS/METHODS: A survey
      was conducted among Belgian dermatologists. In addition to demographic and
      professional characteristics, the questionnaire assessed the self-rated level of
      experience, frequency of use, preference and considerations regarding UVB, PUVA,
      methotrexate (MTX), cyclosporin (CsA) and acitretin. Multivariate logistic
      regression analyses were performed to investigate predictors of these
      dermatologist-based outcomes. RESULTS: Of the 628 contacted dermatologists, 310
      responded (response rate of 49.3%). The dermatologists were significantly more
      experienced with photo(chemo)therapy than with systemic agents (p < or = 0.02);
      about half reported none or little experience with MTX and CsA. Also,
      photo(chemo)therapies were significantly more frequently used than systemic drugs
      (p < or = 0.01). In the last year, almost 40% had not used and less than 10% had
      used MTX or CsA more than 10 times. Despite the limitations of PUVA, it was
      preferred to UVB, followed by acitretin (+/- phototherapy), and MTX and CsA were
      considered final options by most dermatologists. After adjusting for confounding
      variables, age, years in practice, seeing and treating more patients, residency
      programme and/or access to UV therapy were significantly associated with limited
      experience, regular use and/or preference of studied therapies. CONCLUSION:
      Either a substantial proportion of the dermatologists does not need or wish to
      use conventional systemic psoriasis therapies or they may need better and more
      uniform training during and after their residency. This may improve patient care
      and patient selection for other treatments.

PMID- 16902290
TI  - Excimer laser versus narrow-band UVB (311 nm) in the treatment of psoriasis
      vulgaris.
AB  - BACKGROUND: The excimer laser is a new therapeutic option in the treatment of
      psoriasis vulgaris. OBJECTIVE: The purpose of this study was to determine the
      response of psoriasis lesions to the 308-nm excimer laser compared to 311-nm UVB
      phototherapy. METHODS: In this prospective right/left comparative, open, single
      blinded trial, selected psoriasis plaques of 16 patients were treated with the
      excimer laser whereas the rest of the body was treated with UVB narrow-band
      phototherapy. A modified PASI score was used to evaluate the results. RESULTS:
      After 12 treatments, 15 patients were evaluated. In 2 patients no difference
      between the two body sides was observed. In 9 patients the laser-treated lesions
      showed better results, whereas in 4 patients the side treated with 311-nm UVB
      showed more clearing. The mean reduction in PASI score was 5.6 and 4.9,
      respectively (difference not significant). CONCLUSION: The use of the 308-nm
      xenon chloride excimer laser is an additional effective therapeutic option for
      the treatment of psoriasis vulgaris.

PMID- 16902291
TI  - Tumescent power liposuction in the treatment of the enlarged male breast.
AB  - BACKGROUND: Tumescent power liposuction is widely used on various parts of the
      body for minimal-access lipectomy. The undesired fat deposits are injected with
      tumescence fluid containing saline, epinephrine, bicarbonate and lidocaine; the
      latter is used as the only source of pain control. The fat is then removed using
      vibrating microcannulas. OBJECTIVE: To evaluate the value of tumescent power
      liposuction in the treatment of the enlarged male breast. METHODS: 38 male
      patients aged 23-64 years (mean age 39.8 +/- 9.7 years) with enlarged breasts
      were enrolled in the study. In 32 patients, breasts were enlarged due to fat
      tissue, and the ductal glands were not palpable (pseudogynecomastia). In 6
      patients, the ductal glands were enlarged (gynecomastia). All patients were
      treated with tumescent liposuction over a 2-year period using a single entry site
      from the axillary fossa. Both fat as well as ductal and stromal tissue were
      removed by microcannulas. RESULTS: None of the patients had early postoperative
      complications of infection, hematoma or seroma. There were no treatment-induced
      asymmetries, contour deformities or irregularities. No open excision or skin
      reduction procedures were required. CONCLUSION: Tumescent liposuction using a
      single entry site in the axillary fossa is a minimally invasive technique to
      treat enlarged male breasts. Both fat (pseudogynecomastia in adipose patients) as
      well as ductal and stromal tissue (in gynecomastia) can be removed with tumescent
      liposuction, resulting in a high level of patient satisfaction.

PMID- 16902293
TI  - Tempting liver fibrosis? Long-term psoriatic methotrexate therapy and
      heterozygous alpha1-antitrypsin deficiency.
AB  - BACKGROUND: Dermatologists, or pathologists, occasionally need to decide whether
      or not to continue methotrexate therapy in a patient with an identifiable risk
      factor for liver fibrosis, in this instance heterozygous alpha(1)-antitrypsin
      deficiency. CASE PRESENTATION: We relate our experience with an elderly male
      patient, diagnosed as having alpha(1)-antitrypsin deficiency on a liver biopsy,
      genotypically confirmed as PiMZ. He had been receiving methotrexate for psoriasis
      for 17 years with a cumulative dose of 7,200 mg. He was monitored by biochemical
      profiling and interval (10) liver biopsies. Non-specific changes were seen on
      liver histology although grade 1 liver fibrosis was seen in his last 2 biopsies.
      CONCLUSION: We suggest that methotrexate therapy is relatively safe in patients
      with heterozygous alpha(1)-antitrypsin deficiency, with no other risk factor. We
      however advise that the risk of fibrosis should be monitored and that the patient
      receives appropriate counselling.

PMID- 16902292
TI  - Estrogen-receptor-alpha-positive extramammary Paget's disease treated with
      hormonal therapy.
AB  - The patient was an 80-year-old man with scrotal and penile extramammary Paget's
      disease and prostate cancer. Both diseases were in advanced stages. Tumor cells
      of extramammary Paget's disease strongly expressed estrogen receptor alpha. The
      patient was concurrently treated with two kinds of hormonal therapy: the anti
      estrogen tamoxifen (20 mg/day orally) for extramammary Paget's disease and the
      anti-androgen bicalutamide (80 mg/day orally) for prostate cancer. The toxicity
      of the therapy was mild. All of the metastatic lesions remained stable for 2
      months after initiation of dual hormonal therapy. During a follow-up period of 22
      months, performance status was well maintained for 17 months. Hormonal therapy
      may be an alternative for selected cases of advanced extramammary Paget's
      disease.

PMID- 16902294
TI  - Scleromyxedema, a positive effect with thalidomide.
AB  - Scleromyxedema is a rare dermatological disorder marked by widespread symmetric 2
      to 3-mm, firm, waxy, closely spaced papules involving the hands, forearms, face,
      neck, upper trunk and thighs. The most common extracutaneous manifestation of
      scleromyxedema is a benign plasma cell dyscrasia. Treatment of scleromyxedema is
      limited by the lack of long-term results, toxicity and significant adverse side
      effects. We report a severe case of scleromyxedema who had marked improvement
      when treated with thalidomide.

PMID- 16902295
TI  - Missing creases of distal finger joints as a diagnostic clue of nail-patella
      syndrome.
AB  - Nail-patella syndrome (NPS, OMIM 161200) is an autosomal dominant disorder with a
      clinical characteristic tetrad consisting of fingernail dysplasia, hypoplastic or
      absent patellae, bony protuberances of the ilia (iliac horns) and dislocation of
      the radial head. Kidney involvement may lead to renal failure, and there is an
      increased risk for glaucoma. Clinical diagnostic skin clues are triangular
      lunulae especially on the thumbs which are highly predictive for the NPS. A less
      known but even more important sign is the absence of skin creases on the dorsal
      aspects of the distal interphalangeal joints. Even in patients with normal nails
      the absence of distal interphalangeal creases was noted. Less specific skin
      changes are webbing between digits, within the popliteal fossae, hyperextensible
      joints, absent or fragile nails and grooved nails and longitudinal ridging with
      splitting. With increasing costs in the health care system, it is important to
      recognize diseases by specific clinical findings which are often as predictive
      and precise as expensive technical investigations.

PMID- 16902296
TI  - A case of cutaneous T cell pseudolymphoma in a patient with Helicobacter pylori
      infection.
AB  - Cutaneous pseudolymphomas (CPL) are benign cutaneous lymphoproliferative
      infiltrations of various origin, including among others bacterial infections,
      viral infections and drugs . Helicobacter pylori has been frequently founded in
      the stomach of patients with MALT lymphoma. In January 2001, a 43-year-old man
      was referred to our department because of a 1-month history of itchy erythematous
      patches, plaques and flat tumors on his body. Histological examination revealed
      nodular infiltrations composed of lymphocytes, plasma cells and histiocytes with
      exocytosis of lymphocytes within the epidermis. Molecular analysis of
      rearrangement of T cell receptor and immunoglobulin heavy-chain genes did not
      reveal monoclonality. Based on these clinical, laboratory and histopathological
      data, a diagnosis of cutaneous T cell pseudolymphoma (CTPL) was made. The patient
      was anti-H. pylori antibody-positive, and was treated with anti-H. pylori
      combination with the result that all of the tumors had disappeared by January
      2002. The patient has maintained complete response up to the last follow-up visit
      in December 2005.

PMID- 16902297
TI  - Acquired melanocytic naevus in childhood vulval pemphigoid.
AB  - BACKGROUND: Eruptive epidermolysis bullosa (EB) naevi comprise a subset of
      melanocytic naevi with atypical features that characteristically occur in areas
      of former blistering in patients suffering from hereditary EB. OBSERVATION: The
      case is reported of a girl who presented with pruritus, blistering and erosions
      of the vulval region. Clinical and immunopathological features were consistent
      with the diagnosis of childhood vulval pemphigoid. In the course of the disease,
      she developed an atypical melanocytic naevus on the left labium at a site of
      former blistering. Although its clinical and dermoscopic features resembled
      malignant melanoma, the lesion completely regressed clinically during the 24
      month follow-up. CONCLUSION: This is the first report describing the development
      of a melanocytic naevus at sites of blistering in an auto-immune subepidermal
      blistering disease in childhood. Our observation extends the spectrum of
      disorders, in addition to the group of congenital EB, in which 'eruptive'
      atypical melanocytic naevi may occur. Knowledge of this complication is important
      for appropriate management and follow-up and to avoid radical surgery.

PMID- 16902298
TI  - Targeting T cells to hit B cells: successful treatment of cutaneous plasmacytosis
      with topical pimecrolimus.
AB  - Cutaneous plasmacytosis is a rare disease predominantly found in Japanese
      patients. We describe the case of a 75-year-old white female with cutaneous
      plasmacytosis of the face and involvement of the bone marrow. In contrast to
      other cases of cutaneous plasmacytosis, the patient revealed
      hypogammaglobulinemia and elevated levels of free light chains in the urine.
      Treatment with topical pimecrolimus 1%, which primarily targets T cells, led to
      almost complete clinical and histological remission of the skin lesions. Our
      report indicates that the therapeutically induced disappearance of the plasma
      cells was due to indirect T-cell-mediated effects.

PMID- 16902299
TI  - Carbamazepine-induced hypersensitivity syndrome occurring in a photodistributed
      pattern.
AB  - A 76- year- old man was commenced on carbamazepine for partial seizures. This was
      followed by the development of a rash in an apparently photodistributed pattern,
      fever, lymphadenopathy, eosinophilia, abnormal liver function tests and atypical
      lymphocytosis fulfilling the criteria for drug-induced hypersensitivity syndrome.
      Discontinuation of carbamazepine and application of topical steroid resulted in
      clearance of the rash, normalization of liver function tests and improvement in
      eosinophilia. The photodistributed pattern in this case of carbamazepine-induced
      hypersensitivity syndrome is of interest.

PMID- 16902300
TI  - Spores, sporodochia and fomites in onychomycosis.
AB  - Onychomycosis is a frequent infection. Contagion rarely depends on direct
      contamination, but rather on environmental propagule dispersion including the
      intervention of fomites. The potential release of fungal cells in the environment
      from the affected nails has not been thoroughly studied. Observations made by
      histomycology suggest that arthroconidia and chlamydoconidia issued from invading
      fungi can be involved. In addition, the sporodochium, which is an exophytic
      fungal ball, may be attached underneath the distal free edge of some
      onychomycoses. It might represent an important source of fungal propagules in
      patients with poor nail trimming.

PMID- 16902301
TI  - Cutaneous infection by Mycobacterium lentiflavum in a patient with HIV.

PMID- 16902302
TI  - Laminin alpha1-chain may have a role in adnexal morphogenesis.

PMID- 16902303
TI  - Pachydermodactyly in an elderly Japanese patient showing distal involvement of
      the fingers.

PMID- 16902304
TI  - Surgical management of perianal giant condyloma acuminatum (Buschke-Lowenstein
      tumor). Report of three cases.
AB  - Giant condyloma acuminatum (GCA) is a slow-growing, large, cauliflower-like tumor
      located in the anogenital region. This tumor has a locally destructive behavior,
      a high recurrence rate and occasional transformation to squamous cell carcinoma.
      Risk factors include anoreceptive intercourse, HIV and immunosuppression. There
      is no general agreement on the choice of treatment for this tumor. Wide radical
      excision with plastic reconstruction of skin defects seems to be the best
      treatment, while adjuvant therapies, such as radiotherapy and immunotherapy, may
      achieve good results, but their effectiveness is still uncertain. Loop colostomy,
      considered mandatory by several authors in order to minimize wound contamination
      risk, does not appear to be necessary (except in cases of anal canal involvement
      beyond the dentate line) if a combination of bowel cleansing, non-fiber diet and
      loperamide can be administered. The authors report 3 cases of perianal GCA
      treated by radical local excision and reconstruction by S-plasty grafts, without
      performing loop colostomy

PMID- 16902306
TI  - Relation of age-related macular degeneration and cognitive impairment in an older
      population.
AB  - BACKGROUND: The aetiology of age-related macular degeneration (AMD) and cognitive
      impairment is poorly understood. A link between cognitive impairment and AMD has
      been proposed although only a weak association was found in population-based
      studies. PURPOSE: To assess cross-sectional associations between AMD and
      cognitive impairment in an older Australian population. METHODS: The Blue
      Mountains Eye Study examined 3,509 persons aged 49+ years during 1997-2000. AMD
      lesions were assessed from retinal photographs using the Wisconsin System. Mini
      mental state examination (MMSE), demographics, lifestyle factors and medical
      history were collected at interview. MMSE score was categorised as high-normal
      (28-30), low-normal (24-27) and impaired (< 24). A modified MMSE excluded five
      vision related items and was dichotomised as normal (18-22) and impaired (0-17).
      Logistic regression was used to assess associations after adjusting for age, sex,
      visual impairment, stroke, current smoking status, hypertension, alcohol
      consumption and post-high-school qualification. RESULTS: Prevalence rates for
      late and early AMD were 1.5% (n = 50) and 8.3% (n = 273), respectively. Cognitive
      impairment was present in 18.0% in persons with late AMD and 8.4% with early AMD,
      compared to 2.6% in persons without AMD. After multivariate adjustment, late AMD
      was associated with low normal MMSE (odds ratio (OR): 2.2, 95% confidence
      interval (CI): 1.1-5.0) and cognitive impairment (OR: 3.7, CI: 1.3-10.6). Using
      the modified MMSE, the multivariate association between late AMD and cognitive
      impairment remained (OR: 2.2, CI: 1.0-5.0). No significant association was found
      between cognitive impairment and early AMD. CONCLUSIONS: We found a significant,
      cross-sectional association between late AMD and cognitive impairment in a sample
      of older Australians that appeared to be independent of visual impairment. The
      association was weaker but remained significant after excluding vision-related
      items from the MMSE.

PMID- 16902305
TI  - Effects of mexiletine on electrical field stimulation-induced contractile
      responses in the ipsilateral and contralateral vasa deferentia after unilateral
      testicular torsion/detorsion.
AB  - AIM: To investigate testicular torsion-induced changes on the electrical field
      stimulation (EFS)-induced contractions in rabbit vasa deferentia and to evaluate
      the effect of mexiletine. METHODS: 18 male New Zealand albino rabbits were used
      in this experiment. Rabbits were divided into three groups: (1) control group (n
      = 6); (2) torsion group (n = 6), and (3) mexiletine group (n = 6). In the control
      group, vasa deferentia on both sides were harvested. In the torsion and
      mexiletine groups, the left testes of the rabbits were subjected to 720 degrees
      of clockwise torsion for 2 h and then detorsion was performed. In the mexiletine
      group, 50 mg/kg i.p. mexiletine was administered 1 h before detorsion. Following
      24 h of the torsion, vasa deferentia on both sides were harvested and 2-cm strips
      including both the prostatic and epididymal portions were prepared to record EFS
      induced contractions. RESULTS: Testicular torsion caused a significant inhibition
      in both phases of EFS-induced biphasic contractions of the ipsi- and
      contralateral vasa deferentia. Mexiletine treatment did not affect these
      inhibitory responses. Torsion/detorsion of the spermatic cord did not alter
      exogenously applied noradrenaline-induced contractions in both vasa deferentia.
      However, KCl-induced contractions diminished significantly in ipsilateral vas
      deferens of the torsion group and mexiletine restored this inhibition.
      CONCLUSIONS: Unilateral testicular torsion/detorsion leads to inhibition in both
      phases of EFS-induced biphasic contractions of the ipsi- and contralateral vasa
      deferentia by causing a defect in presynaptic nerve transmission. However,
      mexiletine has no effect on this inhibition. Inhibition of the KCl-induced
      contractions in the ipsilateral vas deferens, which indicates postsynaptic tissue
      damage, is restored by administering mexiletine 1 h prior to detorsion.

PMID- 16902307
TI  - Proximal renal tubular acidosis in pregnancy. A case report and literature
      review.
AB  - Renal tubular acidosis is usually associated with chronic renal conditions and is
      rarely encountered in pregnancy. It may be inherited causing osteomalacia and
      rickets in children or acquired following autoimmune diseases or following
      exposure to nephrotoxic agents. It is known to worsen during pregnancy and if
      left untreated may cause maternal and foetal morbidity or death. We report a 28
      year-old woman, gravida 3 para 2, who presented at 30 weeks gestation with
      lethargy, weakness and generalized myalgia. Investigation revealed severe
      hypokalaemia and a systemic metabolic acidosis due to proximal renal tubular
      acidosis. Her previous pregnancies were both complicated by foetal losses at
      term. Following prompt correction of her electrolyte disturbance and metabolic
      acidosis, she went on to deliver a healthy female infant at term. Regular
      evaluation up to 1 year post-partum revealed mild persistence of her
      hypokalaemia. At 1 year, the infant showed no signs of the disorder and is
      growing normally.

PMID- 16902308
TI  - Proposal for the abbreviation of ghrelin--the appetite hormone.

PMID- 16902309
TI  - Vitamin D status in inpatients admitted to an internal medicine department.
AB  - BACKGROUND/AIMS: A role of hypovitaminosis D has been advocated in several
      medical conditions. We investigated vitamin D status in medical inpatients,
      compared to a blood donors' group from the same area. METHODS: Fifty-nine
      consecutive medical patients were recruited at hospital admission, concomitantly
      to 207 blood donors of both genders. Serum calcium, albumin, phosphate,
      creatinine, alkaline phosphatase total activity, 25-hydroxyvitamin D [25(OH)D]
      and parathyroid hormone (PTH) were assessed from April to May 2005. RESULTS: In
      patients, 25(OH)D values were lower (13.1 +/- 9.2 vs. 16.3 +/- 8.5 ng/ml; p <
      0.02) and PTH values higher (73.9 +/- 77.7 vs. 53.4 +/- 24.3 pg/ml; p < 0.01)
      than in controls, whose mean age was lower (62.5 +/- 14.5 vs. 45.8 +/- 15.6
      years, p < 0.01). Such differences were not confirmed when comparing patients to
      a subgroup of age and sex-matched controls drawn from the whole sample of blood
      donors. In both patients and controls there was a trend towards a negative
      correlation between 25(OH)D and age and a positive correlation between PTH and
      age. The prevalence of 25(OH)D <12 ng/ml was higher in patients than in controls
      as a whole (58 vs. 34%; chi(2) = 9.95; p < 0.002), but not in respect to the
      subgroup of matched controls (58 vs. 44%; chi(2) = 2.09; p = 0.14). The
      prevalence of severe vitamin D deficiency, 25(OH)D <5 ng/ml, was significantly
      higher in patients than in matched controls (17 vs. 4%; chi(2) = 6.75; p < 0.01).
      CONCLUSION: Hypovitaminosis D, defined as 25(OH)D <12 ng/ml, is frequent among
      inpatients, as in the general population of comparable age. A severe vitamin D
      deficiency is more common in hospitalized patients.

PMID- 16902310
TI  - Pseudo-pulmonary embolism as a sign of acute heparin-induced thrombocytopenia in
      hemodialysis patients: safety of resuming heparin after disappearance of HIT
      antibodies.
AB  - Heparin-induced thrombocytopenia (HIT) is a syndrome caused by platelet
      activating antibodies that recognize complexes of platelet factor 4 (PF4) and
      heparin. Thrombocytopenia is the most common clinical feature of HIT. HIT can be
      considered as a hypercoagulable state, with a high risk of thrombosis. Another
      feature of HIT is an acute systemic reaction that characteristically begins 5-30
      min after receiving an intravenous bolus of unfractionated heparin, such as is
      commonly given for hemodialysis (HD). Here we present 4 patients who developed
      acute HIT at or near the start of their chronic HD. All patients were
      anticoagulated with the low-molecular-weight heparin, nadroparin, for HD. Three
      of our patients underwent surgery approximately 1-2 weeks before developing HIT.
      All patients presented with an acute systemic reaction during HD. All patients
      were treated and further dialyzed with lepirudin. Under this treatment we
      observed a quick recovery of the platelet count, and patients remained symptom
      free. Antibodies against the PF4-heparin complex were detected with a combination
      of a 'quick test' and an enzyme-linked immunosorbent assay test. The likelihood
      of having HIT previous to the detection of antibodies was estimated with the pre
      test probability score criteria. The tests for PF4-heparin antibodies remained
      positive for an average of 165 days. Three patients underwent a rechallenge with
      nadroparin after disappearance of the HIT antibodies in their serum. All 3
      remained symptomless when they were further hemodialyzed on nadroparin. Our
      observations indicate that nadroparin can be successfully reintroduced for HD
      anticoagulation once the patient's HIT antibodies have disappeared.

PMID- 16902311
TI  - Association of clinic vascular access monitoring practices with clinical outcomes
      in hemodialysis patients.
AB  - BACKGROUND: Early identification of access dysfunctions may be associated with
      improved patient outcomes. We examined whether patient outcomes were associated
      with vascular access monitoring practices in an incident dialysis cohort.
      METHODS: We conducted a national prospective cohort study and analyzed 363
      hemodialysis patients who had a first permanent vascular access (arteriovenous
      fistula or graft) by 6 months after the start of dialysis. Multivariate methods
      were used to examine associations between monitoring practices and 6-month Kt/V
      (reaching Kt/V >/=1.2), access intervention, access failure, and 2-year
      septicemia and all-cause hospitalization and mortality. RESULTS: Patients who
      received monitoring weekly or more often (49%) were more likely to have an access
      intervention (adjusted RH = 1.40, 95% CI, 1.07-1.84) than those who received
      monitoring less frequently. Additionally, patients treated at clinics that
      reported performing regular access monitoring (80% of patients) were less likely
      to be hospitalized for septicemia (IRR = 0.35, 95% CI, 0.21-0.61) or for any
      cause (IRR = 0.77, 95% CI, 0.60-0.99). There were no statistically significant
      differences between patients exposed to different vascular access monitoring
      practices in access failure, achievement of Kt/V, or survival. CONCLUSION:
      Frequent monitoring of dialysis access may initially increase the number of
      interventions but is beneficial to longer-term outcomes, including septicemia
      related and all-cause hospitalization.

PMID- 16902312
TI  - HIT on dialysis--when is it safe to re-challenge?

PMID- 16902313
TI  - Family history associated with improved functional outcome following ischemic
      stroke.
AB  - BACKGROUND: Few studies to date have documented genetic influences on outcomes of
      hospitalization among patients with acute ischemic stroke. OBJECTIVE: To assess
      the influence of the family history of stroke on in-hospital mortality and
      hospitalization outcome among patients having acute ischemic stroke. METHODS: The
      medical records for 916 consecutive adult patients admitted for acute ischemic
      stroke during 12/1/2001-2/28/2002 at 34 randomly selected Georgia hospitals were
      centrally abstracted. The patients were classified as having a positive family
      history of stroke or not. The two groups were compared on risk factors,
      comorbidities, admission characteristics, hospital disposition status, and
      outcome measures. Multivariate logistic regression was used to assess the
      independent contributions of important variables identified by univariate
      screening. RESULTS: A positive family history of stroke was significantly
      associated with a decreased frequency of medical history of coronary artery
      disease, a decreased frequency of medical history of congestive heart failure, an
      increased frequency of medical history of hypertension, and younger age among
      patients with acute ischemic stroke who were 18 years or older. The family
      history was not associated with in-hospital mortality (odds ratio 1.49, 95%
      confidence interval 0.79-2.80 for incident cases). The interaction of family
      history and age was significantly associated with discharge destination and
      discharge functional status. CONCLUSIONS: Preliminary analyses found associations
      between family history and stroke outcome. The role of a family history of stroke
      in stroke outcome merits further study.

PMID- 16902314
TI  - Prevalence of stroke in an Argentine community.
AB  - OBJECTIVE: To determine the prevalence of stroke and its distribution by age, sex
      and clinical type, and to use the outcomes for prevention, care and
      rehabilitation. DESIGN/METHOD: The survey was conducted in Junin, a town of about
      75,000 inhabitants, situated in an agricultural region of the Province of Buenos
      Aires, Argentina. Systematic sampling was used to select 5,839 dwellings
      (sampling fraction approximately 25%) and 5,648 (97%) households participated in
      our study, including 17,049 participants. The initial stage of the study involved
      a case-finding strategy consisting of a two-stage screening approach in the
      selected households; household screening was followed by neurological
      examination. We used a point prevalence with reference date January 1, 1991.
      Stroke was defined according to the WHO criteria. RESULTS: As of January 1, 1991,
      148 subjects were identified as cases of stroke (79.6% ischemic and 20.4%
      hemorrhagic). Point prevalence ratio was 868.1 cases per 100,000 inhabitants in
      the total population (473.4/100,000 age adjusted to the worldwide population) and
      1,867.4 in those patients of 40 years of age or older (1,534.4/100,000 age
      adjusted to the worldwide population). In both sexes, prevalence increased with
      age. However, this increase was more significant and sustained in men of 50 years
      of age and older. Moderate to severe disability was observed in 52% of patients.
      CONCLUSION: This is one of the first community-based studies conducted in
      Argentina about the prevalence of stroke. Final results are similar to those
      reported in other developed countries.

PMID- 16902315
TI  - How does G-CSF act on the kidney during acute tubular injury?
AB  - Recent findings in stem cell research have demonstrated multi-lineage plasticity
      of bone marrow cells, and also the contribution of hematopoietic bone marrow stem
      cells to the regeneration of injured organs including the kidney. These findings
      suggested the possibility of the use of granulocyte colony-stimulating factor (G
      CSF) as a therapeutic option to regenerate injured organs. Recently, several
      studies regarding the effect of G-CSF on renal function have been reported in
      mouse models of acute renal failure. This series of experiments provided
      potentially important information regarding the treatment of patients with renal
      injury. This review summarizes the possible actions of G-CSF on the kidney,
      especially during acute tubular injury caused by toxic or ischemic insults.

PMID- 16902316
TI  - A critical look at growth factors and epithelial-to-mesenchymal transition in the
      adult kidney. Interrelationships between growth factors that regulate EMT in the
      adult kidney.
AB  - In the adult kidney, the cellular phenotypes are maintained by a strict balance
      of growth factors. Epithelial-to-mesenchymal transition (EMT) is a program
      whereby injured epithelial cells that function as ion and fluid transporters
      become matrix remodelling mesenchymal cells. This process requires either
      transcriptional repression of genes that maintain the epithelial phenotype and
      transcriptional activation, or relieved repression of genes needed for functional
      myofibroblasts. The transcriptional regulators are controlled by several
      integrated signalling pathways which are triggered by growth factors. Emerging
      evidence indicates that the growth factors TGFbeta/CTGF and BMP-7/HGF are the
      main determinants that maintain the two cellular phenotypes. Both TGFbeta and BMP
      7 counteract the activity of each other by cross-inducing their respective
      inhibitory Smads. Both growth factors may also induce the expression of other
      factors that can change the cellular environment and enhance their function.
      Chronic kidney diseases (regardless of the aetiology of the disease) are
      associated with increased TGFbeta and CTGF expression levels which, in turn, have
      an inverse effect on the activity level of BMP-7 and HGF, leading to an EMT of
      injured tubular epithelial cells and a progression of the disease. A detailed
      understanding of the complex interrelationship between these growth factors may
      lead to the development of novel drugs.

PMID- 16902317
TI  - Role of carbon monoxide and biliverdin in renal ischemia/reperfusion injury.
AB  - Heme oxygenase (HO) isoforms catalyze the conversion of heme to carbon monoxide
      (CO) and biliverdin/bilirubin with a concurrent release of iron. There is strong
      evidence that HO activity and products play a major role in renoprotection,
      however the exact molecular mechanisms underlying the beneficial effects exerted
      by this pathway are not fully understood. This review is aimed at illustrating
      the possible mechanism/s by which HO is renoprotective in the context of
      ischemia/reperfusion. We will first analyze the effects of exogenous
      administration of bilirubin/biliverdin and CO and then describe their biological
      activities once generated endogenously following stimulation of the HO pathway by
      either pharmacological means or gene targeting-mediated approaches.

PMID- 16902318
TI  - Evidence that the mouse osteocalcin-related gene does not encode nephrocalcin.
AB  - BACKGROUND/AIMS: The osteocalcin-related gene (ORG) is a mouse-specific member of
      the osteocalcin gene cluster predicted to encode a gamma-carboxyglutamic acid
      rich protein. ORG mRNA has been predicted to encode nephrocalcin and shown to be
      expressed in the kidney where it could serve as an important crystallization
      inhibitor. To determine whether ORG encodes mouse nephrocalcin, we investigated
      its in vivo and in vitro expression. METHODS: We expressed fluorescent fusion ORG
      proteins in kidney cell lines and generated transgenic mice expressing enhanced
      green fluorescent protein under the control of the ORG promoter. RESULTS: ORG
      mRNA was shown to be expressed in mouse kidneys and in a variety of other
      tissues. Fusion constructs transfected in opossum kidney cells demonstrated
      integrity of the open reading frame with the presence of a protein of the
      expected molecular weight. However, kidneys from transgenic mice carrying the
      enhanced green fluorescent protein gene under the control of the ORG promoter
      (5.8 kb fragment) demonstrated no expression of the transgene in kidneys or other
      tissues. CONCLUSION: We conclude that ORG, the third gene of the mouse
      osteocalcin gene cluster is silent and unlikely to play a major role in mouse
      renal physiology.

PMID- 16902319
TI  - Renoprotective effect of breviscapine through suppression of renal macrophage
      recruitment in streptozotocin-induced diabetic rats.
AB  - BACKGROUND/AIMS: Experimental and clinical evidence has consistently demonstrated
      that renal macrophage infiltration is one of the most important events for the
      progression of diabetic nephropathy. Breviscapine is a flavonoid extracted from
      the Chinese herb Erigeron breviscapus. Previously, it was shown that treatment
      with breviscapine attenuated renal injury in the diabetic rats. The purpose of
      this study is to investigate whether the renoprotective effect of breviscapine is
      through suppression of renal macrophage recruitment in diabetic rats. METHODS:
      Diabetes was induced bystreptozotocin injection, and breviscapine was
      administered orally at a dose of 20 mg/kg/day for 8 weeks. Control rats received
      vehicle or breviscapine with the same schedule. RESULTS: Breviscapine treatment
      markedly inhibited both an increase of albuminuria and glomeruli hypertrophy and
      tubulointerstitial injury without modifying mean arterial blood pressure and
      creatinine clearance. Levels of malondialdehyde and protein kinase C activities
      were markedly higher and antioxidant enzyme activities such as superoxide
      dismutase, catalase as well as glutathione peroxidase were significantly lower in
      the kidneys of diabetic rats than of the control group, breviscapine
      administration markedly remitted these changes. ED-1-positive cells and
      expression of intercellular adhesion molecule-1 (ICAM-1) and monocyte
      chemoattractant protein-1 (MCP-1) in glomeruli and tubulointerstitium were all
      markedly elevated but were significantly reduced by breviscapine. Western blot
      analysis noted that the expression of transforming growth factor beta1 protein
      was increased 1.8-fold in the kidney in diabetic rats, breviscapine treatment
      could reduce increased expression of TGF-beta1 protein by 47%. CONCLUSION: This
      study describes a novel mechanism by which breviscapine confers a renoprotective
      effect.

PMID- 16902320
TI  - Beneficial effect of TGFbeta antagonism in treating diabetic nephropathy depends
      on when treatment is started.
AB  - BACKGROUND: In diabetic rats with maximal activation of RAS induced by
      uninephrectomy, late treatment with anti-TGFbeta antibody limited renal injury
      only when combined with ACE inhibitor. We investigated whether in a two-kidney
      diabetic model the time at which treatment started predicted the response to
      TGFbeta antagonist. METHODS: 27 weeks after streptozotocin injection, animals had
      mild proteinuria and were randomized to receive irrelevant antibody, anti-TGFbeta
      antibody (1D11) or enalapril till 52 weeks (early treatment). The effect of
      agents alone or combined was also evaluated at the time of overt proteinuria
      (late treatment, 52-61 weeks). RESULTS: When given early, 1D11 displayed marked
      antihypertensive and antiproteinuric effects. Glomerulosclerosis was reduced to
      the extent that a remarkable percentage of glomeruli without sclerosis appeared
      after treatment. Podocyte number was normalized. Renoprotection of 1D11 was
      comparable to enalapril. Despite control of blood pressure, in late treatment
      single agents did not reduce proteinuria significantly. Glomerulosclerosis and
      podocyte loss were partially limited by 1D11 or enalapril, but full protection
      was achieved by combination. CONCLUSIONS: Renoprotective effect of TGFbeta
      antagonism crucially depends on the time at which treatment started.
      Effectiveness of early treatment with 1D11 would indicate that TGFbeta is a major
      mediator of damage in early diabetes. To tackle the renal damage in the phase of
      advanced disease, a combined treatment with ACE inhibitor is needed.

PMID- 16902321
TI  - Aquaporin-2 excretion and renal function during the 1st week of life in preterm
      newborn infants.
AB  - In many preterm infants, a characteristic pattern of fluid and electrolyte
      homeostasis occurs during the 1st week of life, consisting of three phases:
      prediuretic, diuretic, and postdiuretic. In this study, we evaluated the possible
      role of aquaporin-2 (AQP2) in renal concentrating ability and correlated it with
      other markers of the renal function in healthy preterm infants. Daily urine and
      spot blood samples were collected from 9 healthy preterm (32 +/- 1 weeks) infants
      at postnatal ages 1, 3, and 7 days. Urine and serum osmolality, creatinine,
      electrolytes, and AQP2 excretion were measured. All infants showed a significant
      (about 7%) weight loss on day 3 associated with a more than threefold increase in
      urine output without a significant change in fluid intake (diuretic phase). The
      creatinine clearance increased on day 3, indicating an increase in glomerular
      filtration rate. Interestingly, on day 3, the level of total excreted AQP2
      (pmol/h) was significantly higher when compared to day 1 and day 7, and the same
      tendency was observed for urine osmolality. To conclude, the observed increase in
      urine osmolality and creatinine clearance during the diuretic phase, paralleled
      by an increase in total AQP2 excretion, suggests that AQP2 can contribute to the
      urinary concentrating ability early in postnatal life.

PMID- 16902322
TI  - Long-term consequences of early feeding on later obesity risk.
AB  - Some 30 years ago, Gunter Dorner stated that the concentrations of hormones,
      metabolites and neurotransmitters during critical periods of early development
      will program disease risk in human adulthood, a concept that since has received
      enormous scientific support and broad attention. Evidence has also accumulated
      showing that early nutrition programs later obesity risk. Breastfeeding reduces
      the odds ratio for obesity at school age by about 20%, relative to formula
      feeding, adjusted for biological and sociodemographic confounding variables. We
      propose that the protective effect of breastfeeding is explained at least in part
      by the induction of lower rates of infant weight gain, which may be related to
      differences in substrate intakes with breast milk and standard infant formulae.
      Protein intake per kilogram body weight is some 55-80% higher in formula-fed than
      in breast-fed infants. We hypothesize that high early protein intakes in excess
      of metabolic requirements may enhance weight gain in infancy and later obesity
      risk (the 'early protein hypothesis'). The European Childhood Obesity Project is
      testing this hypothesis in a randomized double-blind intervention trial in more
      than 1,000 infants in 5 European countries. Infants that are not breast fed are
      randomized to formulae with higher or lower protein contents and are followed up
      to school age. If an effect of infant feeding habits on later obesity risk should
      be established, there is great potential for effective preventive intervention
      with a significant potential health benefit for the child and adult population.

PMID- 16902323
TI  - Energy requirements of infants and children.
AB  - The energy requirements of infants and children are defined as the amount of food
      energy needed to balance total energy expenditure (TEE) at a desirable level of
      physical activity, and to support optimal growth and development. New TEE data
      from doubly labeled water and heart rate monitoring are available to derive the
      energy requirements. Compared with the 1985 FAO/WHO/UNU recommendations, the 2004
      FAO/WHO/UNU and 2002 IOM recommendations are approximately 12-20% lower during
      infancy. The 2004 FAO/WHO/UNU recommendations are on average 18% lower for boys
      and 20% lower for girls <7 years of age, and 12% lower for boys and 5% lower for
      girls 7-11 years of age. From 12 to 18 years of age, the requirements are 12%
      higher for boys and girls. The 2002 IOM recommendations are 8% lower for children
      <7 years of age, 2% lower for children 7-11 years of age, and 8% higher for
      children 12-18 years of age. Although the basic principles underlying energy
      requirements have not changed, the recommendations for energy intake have been
      decreased in infancy and early childhood, and increased in adolescence based on
      newly available TEE data.

PMID- 16902324
TI  - Protein requirements of infants and children.
AB  - During the last 35 years there have been various published assessments of human
      protein needs, including those of infants and children. Most recently, the
      Institute of Medicine of the US National Academies has published its report on
      Dietary Reference Intakes (DRI) for Macronutrients, and WHO/FAO/UNU have convened
      a new Expert Consultation, which is due to be published soon. Although there have
      been a number of published studies on children's protein requirements determined
      by the nitrogen balance technique, the results of these studies in themselves are
      insufficient to derive requirement values for all ages. Instead, a meta-analysis
      of the data from a range of studies in children has been used to derive values
      for the requirement for maintenance (i.e. no growth), and for the efficiency of
      utilization of dietary protein for growth. These values were then combined with
      age-specific rates of protein deposition to calculate the average requirement at
      any age. New values for protein deposition in children have been derived from
      studies of potassium- 40 accumulation in infants and children, and these have
      been employed in new calculations of the average protein requirement. By
      combining values for the maintenance requirement, derived from adults, with the
      requirement for growth, estimated by analysis of the data for total-body
      potassium at different ages, the age-specific average protein requirement was
      determined. The safe level of intake is the amount of dietary protein that will
      provide the needs of almost all of the specified age group, and this is usually
      taken as the average requirement plus 2 times the standard deviation (SD) of the
      requirement. The SD of the children's requirement was determined by combining the
      SD for maintenance (from the adult data) with the SD for protein deposition,
      derived by combining data for rates of growth of body mass and data for the whole
      body potassium-40 content at different ages. The resulting values for the average
      protein requirement range from 1.12 g/kg/day at age 6 months to 0.74 g/kg/day at
      10 years, with a small decline towards the adult value thereafter. The
      corresponding values for the safe level are 1.43 g/kg/day at 6 months and 0.91
      g/kg/day at 10 years.

PMID- 16902325
TI  - Growth of breast-fed and formula-fed infants.
AB  - Growth and nutrition during infancy are being viewed with renewed interest
      because of the possibility that they may be linked to cardiovascular and
      metabolic health in later life. Of particular interest are differences between
      breast- and formula-fed infants with regard to nutrient intake and growth because
      breastfeeding has been shown to be associated with a reduced risk of obesity in
      later life. During the first 6-8 weeks of life there is little difference in
      growth (gain in weight and length) between breast- and formula-fed infants.
      However, from about 2 months of age to the end of the first year of life formula
      fed infants gain weight and length more rapidly than breast-fed infants. There
      are no consistent differences in adiposity during the first 4-5 months of life,
      but during the later part of the first year of life the preponderance of the
      evidence suggests that breast-fed infants are leaner than formula-fed infants.
      Formula-fed infants at 4-5 months of age show higher plasma levels of insulin
      like growth factor-1 (IGF-1), insulin and certain amino acids than breast-fed
      infants. Whereas the protein intake of breast-fed infants decreases with age and
      closely matches the requirements for protein during the early months of life, the
      protein intake of formula-fed infants exceeds requirements after the first 1-2
      months of life. The data are consistent with the hypothesis that differences in
      protein intake are mainly responsible for differences in growth between breast-
      and formula-fed infants. Differences in energy intake probably are responsible
      for differences in adiposity observed in older infants.

PMID- 16902326
TI  - Body composition during the first year of life.
AB  - Knowledge of changes in body composition is of great potential benefit to the
      understanding of the nutritional needs and functional outcome of nutritional
      management for both healthy and sick infants. This review evaluates the different
      methods presently available to evaluate whole-body composition analysis based on
      different models, i.e. 2, 3, or more compartments. Analysis of the various
      approaches related to age, body weight and body length suggests that the major
      differences observed between the techniques could be preferentially related to
      differences in the population and that gender is one of the major determinants of
      whole-body composition during the first year of life. Among the techniques dual
      energy X-ray absorptiometry (DEXA) and, more recently, air displacement
      plethysmography appear to be major techniques that have been evaluated in
      infants. Determination of weight gain composition is one of the major keys to the
      evaluation of the nutritional requirements, whereas the dynamic aspect during the
      first years of life could play a fundamental role in the nutritional programming
      of adult morbidity. Recent data suggest that protein intake and the
      protein:energy ratio are the main determinants of weight gain composition in
      preterm infants. Nevertheless, these data need to be confirmed in larger cohorts
      evaluated during the first year of life. To that, DEXA appears to be a useful
      technique to obtain sequential analysis of weight gain composition over a longer
      period of time and in a less invasive fashion.

PMID- 16902327
TI  - Dietary reference intakes: concepts and approaches underlying protein and energy
      requirements.
AB  - Nutrient reference values provide guidance for maintaining and enhancing health
      via standard setting and development of nutritionally improved products to
      decrease the risk of disease. Since 1941, the Food and Nutrition Board (FNB) of
      the National Academy of Sciences in the United States has developed and
      periodically revised recommendations for nutrients; the last (10th) edition of
      the Recommended Dietary Allowances (RDA) was released in 1989. In 1994 the FNB
      initiated an expanded approach to develop dietary reference intakes (DRI),
      quantitative nutrient intakes that include concepts of chronic disease risk and
      multiple reference values more specifically suited to various applications. In
      concert with Canadian scientists, 10 DRI reports have been completed since 1997
      and are available for review at www.nap.edu. The DRI reports explicitly review
      possible functional endpoints considered in determining the adequacy of each
      nutrient, and differentiate between the statistical basis for assessing the
      adequacy of intakes for individuals and groups and providing recommended intakes,
      as well as levels of nutrient intake that should not be exceeded. Recommended
      intakes for infants are based on average volumes of intake by healthy, full-term,
      exclusively breast-fed infants and nutrient analysis of human milk; the
      recommended intake also includes nutrients contributed by complementary foods
      consumed during the second 6-month period of life.

PMID- 16902328
TI  - Intestinal amino acid metabolism in neonates.
AB  - The portal-drained viscera (stomach, intestine, pancreas and spleen) have a much
      higher rate of both energy expenditure and protein synthesis than can be
      estimated on the basis of their weight. A high utilization rate of dietary
      nutrients by the portal-drained viscera might result in a low systemic
      availability which determines whole-body growth. From studies in our multiple
      catheterized piglet model, we conclude that more than half of the dietary protein
      intake is utilized within the portal-drained viscera and that amino acids are a
      major fuel source for the visceral organs. Specific stable isotope studies reveal
      that there are large differences in the utilization rate amongst the different
      amino acids. The majority of the results obtained from the piglet studies can be
      extrapolated to the human (preterm) infant. First-pass, splanchnic uptake of
      lysine and threonine differ substantially, while non-essential amino acids are
      oxidized to a great extend in the human gut. Overall, these studies indicate that
      gut amino acid metabolism has a great impact on systemic availability and hence
      growth in the neonate.

PMID- 16902329
TI  - Amino acid requirements of infants and children.
AB  - Nitrogen balances have been conducted in preterm infants, preschool children, and
      6- to 10-year-old children to determine dietary indispensable amino acid. A
      recent review concluded that the data, being sufficiently uncertain, could not be
      used as the basis for defining amino acid requirements in infants and children.
      Therefore, it was decided to use a factorial approach (basal plus growth). This
      approach is based on the assumption that basal requirements are the same
      throughout the life cycle. Recently, using indicator oxidation, the requirements
      of the eight classical indispensable amino acids have been defined in adults.
      These values have been used as the basal component of requirement in childhood.
      The growth component was based on the changes in body protein with age. We have
      recently shown that the maintenance requirements for branched chain amino acids
      are similar in children and adults, thereby validating the factorial approach.

PMID- 16902330
TI  - Effects of high protein intakes.
AB  - Among other nutrients of breast milk, the amino acid pattern is considered
      normative throughout infancy. Exclusive breastfeeding by a healthy mother should
      be the standard from birth to 6 months. During the breastfeeding period the
      protein intake is low in the human being compared too many other animals. The
      protein content in breast milk is about 1 g/100 ml and the daily protein intake
      approximately 1 g/kg/day. When other foods are introduced during the weaning
      period the protein intake increases remarkably to 3-4 g/kg/day in spite of the
      fact that the protein requirement is decreasing. The long-term consequences of
      this phenomenon are obscure. A high protein intake has endocrine effects, such as
      the high levels of insulin and insulin-like growth factor-1. Furthermore, the
      metabolic effects with high levels of urea in serum and urine, and the high
      levels of many amino acids may exceed the capacity of the hepatic and renal
      systems to metabolize and excrete the excess of nitrogen. This may lead to
      acidosis and hypernatremic dehydration during periods of fever and diarrhea.
      Whether the risk of obesity later in life is decreased because of a low intake of
      protein during the breastfeeding period is still obscure.

PMID- 16902331
TI  - Physiology of food intake regulation: interaction with dietary components.
AB  - Food intake is regulated in both the short- and long-term by a complex
      physiological system that involves neuroendocrine pathways that are both distinct
      and overlapping. The underlying causes and mechanisms of the dysregulation of
      food intake in obesity is poorly understood; however, it is clear that dietary
      components interact with the physiological determinants of food intake and can
      cause profound alterations during the development of control mechanisms. The
      objective of this review is to discuss possible food solutions to the obesity
      epidemic based on our current understanding of food intake regulation and its
      interaction with dietary components. First, the physiology of long- and short
      term food intake regulation is reviewed. The effects of dietary components on
      food intake, satiety and intake regulatory markers are then discussed with
      particular emphasis on macronutrient class and source. Finally, the impact of
      nutritional manipulations during the early stages of development on food intake
      and metabolic regulation is examined, followed by a brief description of the
      possible genetic and epigenetic mechanisms involved.

PMID- 16902332
TI  - Complementary food: international comparison on protein and energy
      requirement/intakes.
AB  - The possible role of early dietary habits as the origin of later consequences on
      health has raised questions on the optimal macronutrient intakes of the growing
      infant. Infants and toddlers in developed countries usually show a high dietary
      protein: energy ratio during the complementary feeding period, averaging 2.5-3,
      because of the protein density of solid weaning foods and the low percentage of
      mothers still breastfeeding beyond the first 6 months of life. In conditions of
      very high protein intakes, those in the higher classes of consumption seem to
      carry a higher risk of becoming obese later on. Over the limit of 14% energy from
      proteins in the 8- to 24- month period, some mechanisms may begin to operate
      leading young children towards an early adiposity rebound and overweight
      development. On the other hand, in many developing countries the only available
      weaning foods are cereals, with a low protein: energy ratio value. When the
      protein concentration of weaning foods falls below the limits of human milk (that
      is, from 1 g/100 kcal to lower levels), the infants' dietary requirements cannot
      be met. In planning interventions, the coverage of infants' dietary needs through
      all the various world regions should be considered together with the opportunity
      not to exceed higher limits.

PMID- 16902333
TI  - What is the optimal age for introduction of complementary foods?
AB  - In 2001, a WHO Expert Consultation concluded that waiting until 6 months to
      introduce complementary foods to breastfed infants confers several benefits for
      both infants and mothers. Nonetheless, there is still controversy about this
      issue. In developing countries, the reduced risk of infant gastrointestinal
      illness and increased duration of maternal lactational amenorrhea associated with
      exclusive breastfeeding for 6 months make the benefit-risk ratio of this
      recommendation highly favorable. In industrialized countries, the case is less
      clear-cut, but the benefit-risk ratio is also likely to be favorable with regard
      to infant infectious morbidity, motor development and maternal weight loss
      postpartum. For outcomes such as infant growth, food acceptance and iron or zinc
      status, the evidence for industrialized countries suggests no particular benefit
      but also very little risk of following this recommendation. Some exclusively
      breastfed infants may become iron- or zinc-deficient before 6 months, but this
      can be prevented more effectively by targeted iron and zinc supplementation to
      high-risk infants than by introducing complementary foods. On the whole, the
      evidence to date supports the WHO recommendation to introduce complementary foods
      at 6 months, but further research in industrialized countries would be useful.

PMID- 16902334
TI  - Recent issues in energy-protein malnutrition in children.
AB  - Thirty years ago, protein deficiency was perceived to be the major nutritional
      problem of children in developing countries. Later on increasing the energy
      intake of young children during the complementary feeding period became a
      priority. Early studies on the pathophysiology of malnutrition are now turned
      into strategic and practical consequences for the prevention and treatment of
      severe malnutrition, four of which are presented. (1) Almost half of the deaths
      worldwide are due to being underweight. Nowadays, well-defined preventive and
      curative interventions have been identified. (2) An efficient and rigorous
      technique based on linear programming is now available to design a diet suitable
      for the complementary feeding period using locally available foods with a minimum
      budget to cover the nutritional requirements of at least 97% of the children. (3)
      Managing acute malnutrition in emergencies has greatly improved by the use of a
      spread that a child can eat directly without the addition of water (often called
      Ready-to-Use Therapeutic Food) and Community Therapeutic Care that treats the
      majority of severely malnourished children at home. (4) Recent data strongly
      suggest that it is possible to avoid death due to careful and rapid rehydration
      despite the high purging rate even if many of the risk factors for mortality are
      present in these severely malnourished children. Recovery from malnutrition was
      achieved in 7 days.

PMID- 16902335
TI  - Protein quality and quantity in cow's milk-based formula for healthy term
      infants: past, present and future.
AB  - The development of infant formula with optimized protein quality and quantity has
      been, and still is, the subject of intense investigation. A better understanding
      of the protein composition of breast milk and infant needs in association with
      technological breakthroughs in cow's milk fractionation, has led to the
      development of infant formulas with a protein content that is closer to that of
      human milk. Today, infant formulas with a protein/energy ratio of 1.8 g/100 kcal
      are commercially available. These formulas have been shown to be safe and
      nutritionally adequate for term infants. However, the short-term and potentially
      long-term metabolic benefits of formulas with reduced protein content have still
      to be elucidated and are currently under investigation. In addition to providing
      amino acids as building blocks for growth, milk is the source of numerous
      bioactive factors/hormones which are involved in multiple physiological
      processes. Continuous efforts are being made to identify new bioactive compounds
      in human milk. However, a better understanding of their biological functions in
      suckling infants as well as a comparison with their bovine counterparts are
      needed. Technological processes, which preserve some bioactive factors in cow's
      milk already exist. These processes could be applied to infant formulas.

PMID- 16902336
TI  - Recombinant human milk proteins.
AB  - Human milk provides proteins that benefit newborn infants. They not only provide
      amino acids, but also facilitate the absorption of nutrients, stimulate growth
      and development of the intestine, modulate immune function, and aid in the
      digestion of other nutrients. Breastfed infants have a lower prevalence of
      infections than formula-fed infants. Since many women in industrialized countries
      choose not to breastfeed, and an increasing proportion of women in developing
      countries are advised not to breastfeed because of the risk of HIV transmission,
      incorporation of recombinant human milk proteins into infant foods is likely to
      be beneficial. We are expressing human milk proteins known to have anti-infective
      activity in rice. Since rice is a normal constituent of the diet of infants and
      children, limited purification of the proteins is required. Lactoferrin has
      antimicrobial and iron-binding activities. Lysozyme is an enzyme that is
      bactericidal and also acts synergistically with lactoferrin. These recombinant
      proteins have biological activities identical to their native counterparts. They
      are equally resistant to heat processing, which is necessary for food
      applications, and to acid and proteolytic enzymes which are needed to maintain
      their biological activity in the gastrointestinal tract of infants. These
      recombinant human milk proteins may be incorporated into infant formulas, baby
      foods and complementary foods, and used with the goal to reduce infectious
      diseases.

PMID- 16902337
TI  - Depressed skull fractures in children: Treatment using an obstetrical vacuum
      extractor.
AB  - INTRODUCTION: A depressed skull fracture is an inward buckling of the skull
      bones. It is referred to as a ping-pong ball fracture in neonates; in older
      children, some fractures take a cup shape mimicking 'ping-pong' ball fractures.
      OBJECTIVE AND METHODS: The aim of this study was to assess the use of an
      obstetric vacuum extractor to elevate cup-shaped depressed skull fractures in
      children irrespective of age. All children admitted into the Central Hospital of
      Yaounde between 1999 and 2004 with a cup-shaped simple depressed skull fracture
      and treated with the vacuum extractor were included. RESULTS: Nine children aged
      from 3 months to 17 years were treated with the vacuum extractor. The cosmetic
      and radiographic results were satisfactory. The procedure was simple and without
      any complication. CONCLUSION: The elevation of 'ping-pong-ball-like' or 'cup
      shaped' skull fractures in older children (beyond the neonatal period) is a
      simple, effective and safe procedure.

PMID- 16902338
TI  - Pattern and factors affecting management outcome of spina bifida cystica in Ile
      Ife, Nigeria.
AB  - BACKGROUND AND OBJECTIVE: There is paucity of data on the pattern and factors
      affecting the management outcome of patients with spina bifida cystica in the Ife
      Ijesa zone, Nigeria. This study was designed to address this research question.
      METHOD: One hundred and six consecutive cases of spina bifida cystica who
      presented in our hospital from January 1990 to December 2004 were reviewed. We
      obtained information on sociodemographic factors, medical history and management
      as well as clinical outcome. SPSS was used to analyze the data. RESULT: Males
      constituted 54.7% and females 45.2% of cases. Mortality was high in those
      presented after the 4th week of life (p = 0.04). The malformation occurred in the
      lumbar and lumbosacral regions in 77.4%. Myelomeningocele was the most common
      type (86.8%). Hydrocephalus was recorded in 53.8% of patients. Surgical closure
      was done for 91.5% of the patients. About 77% of all the patients were discharged
      while 22.7% died. This was significantly related to age at presentation (p =
      0.04) and infection before surgery (p = 0.045). Postoperative complications were
      more frequent in patients with ruptured lesions (p = 0.025), a larger size of
      defect (p = 0.028) and a lower birth weight (p = 0.006). CONCLUSION:
      Myelomeningocele is the most common type of spina bifida cystica in our
      environment. Late presentation and preoperative infection are associated with
      high mortality in our patients.

PMID- 16902340
TI  - Treatment of craniosynostosis by distraction osteogenesis.
AB  - PURPOSE: Craniosynostosis patients treated with one-stage cranioplasty often have
      bleeding from the dura mater, fluid collection in the extradural space, and poor
      wound healing due to skin overstretching. To avoid these complications, we began
      using distraction osteogenesis. To determine the advantages and disadvantages of
      the procedure, we retrospectively compared distraction osteogenesis with
      conventional cranioplasty. PATIENTS AND RESULTS: We treated 24 patients with
      fronto-orbital advancement. Fifteen had one-stage cranioplasty; 9 received
      distraction osteogenesis. The one-stage operation patients averaged 25.5 months
      of age at surgery, 289 min of operating time, and 154 ml of intraoperative blood
      loss. For the distraction group, the average age was 16.6 months, average
      operating time was 196 min, and average blood loss was 76 ml. CONCLUSIONS:
      Compared with one-stage cranioplasty patients, distraction osteogenesis patients
      had significantly less intraoperative bleeding and shorter operating times. The
      disadvantages of distraction treatment were the need for multiple surgeries,
      prolonged hospitalization, wound infection, and dislocation of the distraction
      device.

PMID- 16902339
TI  - Low incidence of subdural grid-related complications in prolonged pediatric EEG
      monitoring.
AB  - Invasive EEG monitoring is one of the best tools available for localization of
      epileptogenic foci in the brain. However, published data in mixed series of adult
      and pediatric patients show high incidence of epidural bacterial contamination,
      cerebrospinal fluid leakage, and skin infection after subdural electrode
      implantation. We sought to determine whether the complication rate from prolonged
      subdural electrode implantation would be lower in a purely pediatric series.
      Thirty-three subdural electrode implantation procedures were performed in 29
      pediatric patients (age range 4-19) for an average of 7.2 days (range 3-14 days).
      Electrode number varied from 32 to >128 with a range of 4-11 electrode wires
      piercing the skin >1 cm from the primary incision. Of the 33 implantations and
      resections (66 craniotomies), 5 were for reimplantation. There were no permanent
      complications related to grid implantation. Transient complications included 1
      case of prolonged prothrombin time and 1 patient with unexplained fever, both of
      which resolved upon removal of the grids. There were two culture-positive
      infections, one epidural and one superficial, both in patients undergoing
      reimplantation. There was no percutaneous cerebrospinal fluid leakage noted and
      no operation was aborted due to bleeding caused by grid placement. Our data
      suggest that subdural grid implantation in children is remarkably safe even for
      prolonged implantation, though infectious risk is significantly higher in
      reoperation (p = 0.019). This observation may contribute to lowering the
      threshold for two-stage invasive monitoring approaches in children with epilepsy.

PMID- 16902341
TI  - Surgical treatment outcome of subdural empyema: A clinical study.
AB  - A retrospective study of 28 patients identified with subdural empyema (SE) at the
      Department of Neurosurgery between the years 1995 and 2005 was carried out. SE
      occurred in all patients following bacterial meningitis. The six most frequently
      encountered clinical features included: (1) fever in 22 (79%) patients; (2)
      disturbed consciousness in 16 (57%) patients; (3) papilledema in 11 (39%)
      patients; (4) hemiparesis in 4 (14%) patients; (5) meningismus or meningeal signs
      in 4 (14%) patients, and (6) seizures in 3 (11%) patients. In the majority of
      cases, the most frequent causative pathogen of SE was Staphylococcus aureus.
      Surgery was performed on all patients, which included craniotomy in a group of 20
      patients and burr hole drainage in a group of 8 patients. In conclusion, we
      believe that infants and young children should be carefully monitored following
      meningitis, in case of SE development, and that surgical intervention in patients
      presenting with meningitis may facilitate the development of SE. Furthermore,
      from a surgical point of view, our experience has led us to believe that
      craniotomy in comparison with burr hole surgery is the best surgical modality for
      management of SE as the recurrence rate of SE associated with burr hole surgery
      is high.

PMID- 16902342
TI  - Unusual clinical and MRI features of a cerebellopontine angle medulloepithelioma.
      Case report and review of literature.
AB  - We describe for the first time an unusual location and clinical presentation of
      medulloepithelioma, a rare embryonal tumor. A 5-year-old child presented with
      sudden onset of bilateral hearing loss. On imaging, the lesion appeared to be
      extra axial and was located in the right cerebello-pontine (CP) angle, extending
      into middle fossa along the trigeminal ganglion and in front of the brain stem
      into the opposite CP angle. It did not show any enhancement following contrast
      administration and had restricted diffusion on diffusion-weighted imaging,
      simulating an epidermoid. However, in vivo localized proton MR spectroscopy
      revealed a creatine peak dominated by a large choline resonance, peak of glycine
      with lactate/lipid and invisible N-acetylaspartate suggestive of a neoplastic
      lesion and not an epidermoid. Only subtotal resection could be performed and the
      patient had a stormy post-operative course due to extensive dissemination of the
      disease.

PMID- 16902343
TI  - Osteochondroma of the cervical spine extending multiple segments with cord
      compression.
AB  - Involvement of the cervical spinal cord by a solitary osteochondroma is rare. We
      describe a case of cervical osteochondroma extending from C5 to C7 in a 16-year
      old male. The tumor, arising from the inner aspect of the C6 spinous process,
      projected longitudinally into the spinal canal and compressed the spinal cord;
      this caused clinical symptoms associated with myelopathy and radiculopathy. Total
      excision of the tumor by C5-C7 hemilaminectomy resulted in a good functional
      recovery.

PMID- 16902344
TI  - Head injury caused by an ostrich: A rare entity.
AB  - Human injuries caused by animals are not uncommon and have been reported in the
      literature on many occasions. Most of the animals commonly involved are dogs,
      cats, cows, horses and camels. Injuries are usually on the trunk or limbs and
      sometimes on the face. Human injuries caused by an ostrich are rare and only
      three cases have been reported with severe ocular injury. To our knowledge, this
      is the first reported case of head injury caused by an ostrich in a child.

PMID- 16902345
TI  - Excision of juvenile pilocytic astrocytoma of the midbrain after radiotherapy.
AB  - A 13-year-old girl presented with consciousness disturbance, right hemiparesis,
      and impairment of hearing, swallowing, and ocular movements. A magnetic resonance
      image demonstrated marked hydrocephalus due to a large cystic tumor (40 x 40 x 30
      mm) in the midbrain. Emergency ventricular drainage and stereotactic cyst
      puncture dramatically improved her condition. Since her family did not agree to
      surgery on the brain stem, radiotherapy was performed after ventriculoperitoneal
      shunting. Conventional radiotherapy of 50.4 Gy was temporarily effective, and the
      growth of the tumor was stabilized until approximately 8 months later when
      regrowth was noticed. At this stage, with the consent of her family, the tumor
      was removed via an infratentorial supracerebellar approach. The pathological
      diagnosis was juvenile pilocytic astrocytoma. The postoperative course was
      uneventful. No recurrence has been observed during the follow-up period of more
      than 6 years. This case study shows that initial excision may be appropriate for
      some low-grade focal lesions in the midbrain when the histological diagnosis and
      consent have been obtained.

PMID- 16902346
TI  - Seven distinct coexistent cranial and spinal anomalies.
AB  - Existence of multiple cranial and spinal anomalies in spina bifida is well known;
      however, coexistence of seven different severe anomalies is extremely rare. The
      location of the anomalies, the patient's age and presentation are other
      interesting aspects of the presented case. CASE REPORT: A 1-year-old girl with an
      enlarged head and big, infected lumbosacral myelomeningocele (MMC) was admitted
      to the emergency department in a comatose state. Further investigations revealed
      hydrocephalus, Chiari malformation, syringohydromyelia, split cord malformation,
      dermal sinus tract, lumbosacral MMC, and tethered cord. Unfortunately, the
      patient died 3 days after admission because of meningitis and sepsis. DISCUSSION:
      Coexistence of seven different craniospinal anomalies is extremely unusual.
      Further investigations with magnetic resonance imaging for associated anomalies,
      early shunt placement and MMC repair are required to prevent this life
      threatening condition in spina bifida.

PMID- 16902347
TI  - Cystic meningioangiomatosis.
AB  - A case of cerebral meningioangiomatosis with rare cyst formation is reported. A
      14-year-old boy without any stigmata of neurofibromatosis type 2 presented
      intractable complex partial and generalized seizures since the age of 12 years.
      Neuroradiological studies showed an abnormal cystic mass with calcification in
      the left frontal lobe of the cerebrum. The tumor was located in the leptomeninges
      and cerebral cortex. The patient underwent surgical treatment because medical
      treatment with phenytoin and sodium valproate was not sufficient to control the
      seizures. An intraoperative electrocorticogram revealed that epileptic foci were
      recorded from the cortex, which was adjacent to the lesion. Histopathology showed
      specific features of meningioangiomatosis with meningioma-like nodules. The
      patient did not have any seizures with anticonvulsants after surgery. It is
      important to distinguish meningioangiomatosis from other possible cortical
      lesions and epileptic foci should be carefully considered before resection,
      because it is a benign and surgically manageable cause of seizures.

PMID- 16902348
TI  - Aneurysmal bone cyst of the orbit.
AB  - We report the case of an aneurysmal bone cyst of the left orbital roof in a 12
      year-old boy who presented proptosis of the left eye and painless swelling of the
      left orbital rim. A 3-cm-large tumor developed in less than 3 months, with first
      visible signs about 2 months after a minor head injury. Radiologically, the
      lesion was osteolytic and multicystic. The cyst, filled with hematic fluid, was
      surgically removed via left frontal craniotomy and a simple curettage with high
      speed bur. The patient recovered well and has been in good health throughout 14
      months of follow-up.

PMID- 16902349
TI  - Internal reduction established by occiput-C2 pedicle polyaxial screw
      stabilization in pediatric atlantoaxial rotatory fixation.
AB  - Atlantoaxial rotatory fixation is an uncommon disorder of childhood, which can be
      treated conservatively when diagnosed early. Although spontaneous correction
      occasionally occurs, most of the patients usually benefit from collar or traction
      therapies. If there is no intervention or if all external therapeutic modalities
      fail, the deformity may become chronic and irreducible. In such rare cases,
      surgical correction and stabilization are needed to prevent future head and neck
      deformity or facial asymmetry. In this report we describe a novel surgical
      technique used in a pediatric case presenting with delayed type 2 atlantoaxial
      rotatory fixation, in whom all external reduction methods had failed. The
      patient's deformity was treated by occiput-C2 pedicle polyaxial screw
      stabilization. This technique is effective for reducing the atlantoaxial fixation
      in children.

PMID- 16902350
TI  - Meckel-Gruber syndrome in association with an occipital meningocele.

PMID- 16902351
TI  - Transethmoidal transpharyngeal nasal encephalocele: Neuroimaging.

PMID- 16902352
TI  - Giant vestibular schwannoma in a 12-year-old girl.

PMID- 16902353
TI  - Examining the support for evidence-based nursing practice.

PMID- 16902354
TI  - The Partnership Care Delivery Model.

PMID- 16902355
TI  - From cheerleader to patent processor.

PMID- 16902357
TI  - Bachelor of science in nursing completion: A matter of patient safety.

PMID- 16902358
TI  - Hospital initiatives to support a better-educated workforce.
AB  - A 2003 article in the Journal of the American Medical Association documented that
      mortality rates from common surgical procedures were significantly lower in
      hospitals employing more staff nurses prepared at the baccalaureate level. In
      this report, that study's authors review case studies of 6 hospitals that
      demonstrate the kinds of initiatives employers are sponsoring to support a better
      educated nurse workforce.

PMID- 16902360
TI  - Prioritizing safe patient handling: The American Nurses Association's Handle With
      Care Campaign.
AB  - Nurses continue to suffer debilitating injuries secondary to manual patient
      handling. Patient care ergonomics has emerged to redesign patient care with
      reduced exposure to physical hazards. Safe patient handling programs are being
      increasingly accepted by healthcare organizations to prevent occupational injury
      and to enhance patient safety. The authors discuss national-level efforts to
      promote patient care ergonomics principles and safe patient handling programs and
      their impact on nursing shortages and quality patient care.

PMID- 16902361
TI  - Nonpunitive medication error reporting: 3-year findings from one hospital's
      Primum Non Nocere initiative.
AB  - OBJECTIVE: To identify underlying practices and attitudes on medication error
      occurrences and reporting practices. BACKGROUND: In response to a hospital-wide
      quality improvement initiative, a task force was formed to facilitate a
      nonpunitive culture toward reporting medication errors. To identify underlying
      practices and attitudes on medication errors and medication error reporting, a
      baseline survey was conducted. Based on findings, an initiative that included
      modifications to clinical and administrative processes was developed and
      implemented. METHODS: A pre/post initiative questionnaire to measure staff
      practices and attitudes on medication error reporting was developed and
      administered. Findings from the presurvey were used to craft the Nonpunitive
      Patient Safety Policy and its implementation plan. Pre-post comparative analysis
      was performed following a baseline-postimplementation design. RESULTS:
      Conceptually, a medication error is qualified by its outcome severity. Medication
      errors with more serious outcomes are more likely to be reported than those with
      less serious ones. Staff perception that medication error reporting carries the
      risks of disciplinary action was identified as a primary barrier to the
      likelihood of reporting. CONCLUSION: Evaluation of the initiative suggests that a
      multicomponent approach facilitates positive movement in the direction of a
      nonpunitive culture toward reporting medication errors.

PMID- 16902362
TI  - A Magnet community hospital: Fewer barriers to nursing research utilization.
AB  - OBJECTIVE: To identify the barriers to research utilization for nurses within a
      Magnet community hospital. DESIGN: A descriptive, quantitative design was used.
      METHODS: The instrument used was the BARRIERS scale, a 29-item Likert-type
      questionnaire, regarding perceived obstacles to research utilization. It included
      3 open-ended questions. In all, 584 packets containing the BARRIERS tool and a
      demographic survey were successfully distributed. A total of 275 (47%) completed
      questionnaires were returned. RESULTS: The questions were categorized into 4
      domains: Nurse, Setting, Research, and Presentation. The Setting domain was found
      to be the greatest barrier for nurses. Four of the top 5 barriers related to the
      Setting. Facilitators to implementing research fell within 4 distinct themes:
      access and availability, education and communication, practical application, and
      supportive environment. A statistically significant difference was found in the
      Nurse domain based on the education level (F = 2.932) (P = .034). CONCLUSIONS:
      The results of this study will be useful in determining strategies for improving
      the nurse practice setting to facilitate the use of research by nurses. Suggested
      changes should encourage the reading of research; discussion of research; risk
      taking to implement new ideas; mentoring; and education of nursing staff,
      hospital administration, and physicians. Implementation of the Magnet standards
      is likely to diminish the barriers to research use by nurses within that
      facility.

PMID- 16902365
TI  - NC-stat as a screening tool for carpal tunnel syndrome.

PMID- 16902366
TI  - Pitfalls in the study using death certificates to demonstrate the reversibility
      of mortality from diabetes in the blackfoot disease endemic areas in Taiwan.

PMID- 16902368
TI  - Community exposure to perfluorooctanoate: relationships between serum
      concentrations and exposure sources.
AB  - OBJECTIVE: The objective of this study was to determine serum (perfluorooctanoate
      [PFOA]) in residents near a fluoropolymer production facility: the contributions
      from air, water, and occupational exposures, personal and dietary habits, and
      relationships to age and gender. METHODS: The authors conducted questionnaire and
      serum PFOA measurements in a stratified random sample and volunteers residing in
      locations with the same residential water supply but with higher and lower
      potential air PFOA exposure. RESULTS: Serum (PFOA) greatly exceeded general
      population medians. Occupational exposure from production processes using PFOA
      and residential water had additive effects; no other occupations contributed.
      Serum (PFOA) depended on the source of residential drinking water, and not
      potential air exposure. For public water users, the best-fit model included age,
      tap water drinks per day, servings of home-grown fruit and vegetables, and carbon
      filter use. CONCLUSIONS: Residential water source was the primary determinant of
      serum (PFOA).

PMID- 16902369
TI  - Community exposure to perfluorooctanoate: relationships between serum levels and
      certain health parameters.
AB  - OBJECTIVE: The objective of this study was to determine whether certain
      biomarkers of toxicity and/or a past diagnosis of liver or thyroid disease were
      associated with serum perfluorooctanoate concentrations (PFOA) in a community
      with longstanding environmental exposure to PFOA. METHODS: Serum (PFOA),
      hematologic and biochemical biomarkers, and a questionnaire were administered to
      371 residents selected by stratified random sampling and a lottery among
      volunteers. Median PFOA was 354 ng/mL (interquartile range, 181-571 ng/mL).
      RESULTS: No significant positive relationships between serum (PFOA) and liver or
      renal function tests, cholesterol, thyroid-stimulating hormone, or with red cell
      indices, white cell, or platelet counts. Mean serum (PFOA) was not increased in
      those with a history of liver or thyroid disease. CONCLUSIONS: No toxicity from
      PFOA was demonstrated using the measured end points; other end points need to be
      addressed.

PMID- 16902370
TI  - Short-term effects of air pollution on heart rate variability in senior adults in
      Steubenville, Ohio.
AB  - OBJECTIVE: We examined the association between ambient air pollution levels and
      heart rate variability (HRV) in a panel study of 32 subjects. METHODS: We used
      linear mixed models to analyze the effects of fine particles (PM2.5), sulfate
      (SO4), elemental carbon (EC), and gases on log-transformed standard deviation of
      normal RR intervals (SDNN), mean square of differences between adjacent RR
      intervals (r-MSSD), and high- and low-frequency power (HF, LF). RESULTS: An
      interquartile range (IQR) increase of 5.1 mug/m in SO4 on the previous day was
      associated with a decrease of -3.3% SDNN (95% confidence = -6.0% to -0.5%), -5.6%
      r-MSSD (-10.7% to -0.2%), and -10.3% HF (-19.5% to -0.1%). Associations with
      total PM2.5 were similar. HRV was not associated with EC, NO2, SO2, or O3.
      CONCLUSION: In addition to traffic-related particles, elevated levels of sulfate
      particles may also adversely affect autonomic function.

PMID- 16902371
TI  - Lipid peroxidation in workers exposed to aluminium, gallium, indium, arsenic, and
      antimony in the optoelectronic industry.
AB  - OBJECTIVE: The objective of this study was to investigate whether exposure to
      aluminum, gallium, indium, arsenic, and antimony induces lipid peroxidation in
      humans. METHODS: Whole blood and urine levels of 103 exposed electronic industry
      workers and 67 referents were analyzed by use of inductively coupled plasma mass
      spectrometry. Malondialdehyde (MDA), the product of lipid peroxidation, was
      determined by high-performance liquid chromatography. RESULTS: The mean plasma
      MDA level in the 103 workers was significantly higher than that in 67 referents.
      The levels of MDA in the exposed workers were correlated significantly with the
      levels of urinary gallium and arsenic. CONCLUSIONS: Malondialdehyde as an index
      of lipid peroxidation can be induced by gallium and arsenic exposure. By reducing
      exposure to these metals, biologic effects such as lipid peroxidation may also be
      diminished.

PMID- 16902372
TI  - Healthcare and workloss costs associated with patients with persistent asthma in
      a privately insured population.
AB  - OBJECTIVE: The objective of this study was to estimate annual healthcare and
      workloss costs of patients with persistent asthma by severity. METHODS: A
      persistent asthma patient sample (<65 years) was selected from an employer claims
      database. Asthma persistence and severity were determined by a novel algorithm
      based on Health Plan Employer Data and Information Set criteria, Leidy's Reliever
      and Oral Steroid Method, and Global Initiative for Asthma guidelines. Healthcare
      costs were compared between asthma patients and demographically matched controls
      and by asthma severity. RESULTS: Average annual excess costs for persistent
      patients were $4412 for health care and $924 for workloss (P < 0.01). Although
      costs for severe patients were higher than moderate patients (P < 0.05), moderate
      patients' costs were similar to that for mild patients. Persistent use of inhaled
      corticosteroids was lower in mild (9.0%) relative to moderate (78.1%) and severe
      (86.4%) patients. CONCLUSIONS: Persistent asthma is expensive. Underutilization
      of inhaled corticosteroids is higher in patients with mild persistent asthma.

PMID- 16902373
TI  - Duration dependence in sickness absence: how can we optimize disability
      management intervention strategies?
AB  - OBJECTIVE: The optimal timing of interventions during sickness absence remains
      difficult to determine, because we do not have a clear picture of the presence
      and type of duration dependence that exists. This study investigates the impact
      of an intervention by the occupational physician as well as of socioeconomic and
      work-related factors on duration dependence during sickness absence. METHODS:
      Analyses were performed at the population level using data from a major
      longitudinal survey on work incapacity and return to work in The Netherlands.
      Several models of duration dependence are estimated. RESULTS: Evidence is found
      for the presence of variable-duration dependence. Characteristics that influence
      duration dependence of the return-to-work (RTW) rate are identified. CONCLUSIONS:
      The findings imply that RTW intervention strategies should vary according to
      differences in workers' susceptibility to positive or negative duration
      dependence effects.

PMID- 16902374
TI  - Exposure evaluation to airborne polycyclic aromatic hydrocarbons in an italian
      airport.
AB  - The aim of this study was to use environmental monitoring to evaluate
      occupational exposure to polycyclic aromatic hydrocarbons (PAHs) and biphenyl in
      an Italian airport. Air was sampled using a quartz fiber filter, a polyurethane
      foam, and an XAD-2 layer. After extraction with dichloromethane, concentration
      and purification analyses of 25 PAHs (including biphenyl) were carried out by gas
      chromatography-ion trap mass spectrometry. In winter 2005, 12 air samples were
      taken at 120 L/min for 24 hours in three different areas of the airport. PAH
      levels were found to be generally low. In all investigated areas, the higher
      levels refer to naphthalene (130-13,050 ng/m), 2-methylnaphthalene (64-28,500
      ng/m), 1-methylnaphtalene (24-35,300 ng/m), and biphenyl (24-1610 ng/m). However,
      in some instances, for compounds such as benzo[b+j+k]fluoranthene and
      benzo[a]pyrene, two high-boiling PAHs, the levels found (54.2 ng/ m and 8.6 ng/m,
      respectively) can be considered of some concern.

PMID- 16902375
TI  - Occupation and lung cancer mortality in a nationally representative U.S. Cohort:
      The National Health Interview Survey (NHIS).
AB  - OBJECTIVE: The objective of this study was to assess the risk of lung cancer
      mortality in a nationally representative sample of U.S. workers by occupation.
      METHODS: National Death Index linkage identified 1812 lung cancer deaths among
      143,863 workers who participated in the 1987, 1988, and 1990-1994 National Health
      Interview Surveys. RESULTS: Current and former smoking status was predictive of
      lung cancer mortality (hazard ratio [HR] = 15.1 and 3.8, respectively).
      Occupations with significantly higher risk for age- and smoking-adjusted lung
      cancer mortality included heating/air/refrigeration mechanics (HR = 3.0); not
      specified mechanics and repairers (HR = 2.8); financial records processing
      occupations (HR = 1.8); freight, stock, and materials handlers (HR = 1.5); and
      precision production occupations (HR = 1.4). CONCLUSION: Although tobacco use
      continues to be the single most important risk factor for lung cancer mortality,
      occupational exposure to lung carcinogens should be targeted as well to further
      reduce the burden of lung cancer.

PMID- 16902376
TI  - Prevalence of workplace exacerbation of asthma symptoms in an urban working
      population of asthmatics.
AB  - OBJECTIVES: We used an interviewer-administered questionnaire to investigate
      workplace exacerbation of asthma symptoms (WEAS) among low-income, minority,
      working asthmatics admitted Bellevue Hospital Center in New York City from 2001
      to 2002. We hypothesized that a high prevalence of WEAS would be found in this
      population among all jobs held and a subset of individual occupational
      classifications. MEASUREMENTS AND MAIN RESULTS: Of 301 subjects, 51% reported
      WEAS in their current or most recent job; 71% reported WEAS in any job.
      Prevalences (95% confidence intervals) of WEAS in common job classifications were
      61% (49-73%) in janitorial jobs, 50% (33-67%) in garment and textile
      manufacturing jobs, and 38% (23-55%) in construction jobs. CONCLUSION: WEAS is
      prevalent in this urban minority population.

PMID- 16902377
TI  - Prioritizing industries for occupational injury and illness prevention and
      research, Washington State Workers' compensation claims, 1999-2003.
AB  - OBJECTIVE: The objective of this study was to identify high-risk industry groups
      for effective allocation of occupational safety and health prevention and
      research resources. METHODS: We used all compensable Washington state workers'
      compensation claims to rank North American Industry Classification System (NAICS)
      industry groups by a "prevention index" (PI). The PI is the average of the rank
      orders of each industry group's claim count and claim incidence rate. RESULTS: Of
      the 274 industry groups ranked by PI for all compensable workers' compensation
      claims, the following industry groups ranked the highest: NAICS 2381 Foundation,
      Structure, and Building Exterior Contractors, NAICS 4841 General Freight
      Trucking, and NAICS 2361 Residential Building Construction. Industry group PI
      rankings are reported for the seven most common costly occupational injury types.
      CONCLUSIONS: Use of a PI can focus prevention and research resources where they
      can be of most benefit.

PMID- 16902380
TI  - Ich Weiss Nicht Was Soll Es Bedeuten: language matters in Medicine.

PMID- 16902378
TI  - Specific molds associated with asthma in water-damaged homes.
AB  - OBJECTIVE: We sought to determine if specific molds were found in significantly
      higher concentrations in the water-damaged homes of asthmatic children compared
      with homes with no visible water damage. METHODS: The mold concentrations in the
      dust in asthmatic children's bedrooms in water-damaged homes (N = 60) and control
      homes (N = 22) were measured by mold-specific quantitative polymerase chain
      reaction. RESULTS: Two molds, Scopulariopsis brevicaulis and Trichoderma viride,
      had significantly (P < 0.05) higher concentrations in asthmatics' homes compared
      with control homes and three other molds (Penicillium crustosum group,
      Stachybotrys chartarum, and Wallemia sebi) had P values <0.1. CONCLUSIONS: A
      relative moldiness index was developed to predict the likely development of
      asthma in water-damaged homes in Cleveland.

PMID- 16902381
TI  - [Dental status, access to care and precariousness].
AB  - BACKGROUND: The oral status of people living in precarious conditions is
      problematic. Although the public universal health insurance should allow better
      access to care, access to dental care remains a critical issue. The analysis of
      the patient population of a hospital dental consultation (Groupe Pitie
      Salpetriere, Paris) seemed relevant to evaluate the needs of care and the means
      to provide it. The principal objectives are: to estimate dental health and needs
      of this population, to describe their sociodemographic characteristics and to
      compare them with patients living in common social conditions. METHODS: A cross
      sectional study was conducted from February to June 2003. A medical questionnaire
      and a dental file record were used. All outpatients coming to the dental
      consultation, in need of conservative or prosthetic treatment, were included. We
      analysed the risk factors associated with poor dental health. RESULTS: Three
      hundred and thirty three questionnaires were analysed: two third were men, 45%
      were foreigners. More than half of them benefited from a special social health
      insurance for disadvantaged people or didn't have any health insurance. The
      comparative analysis of this precarious group vs regular insured people showed
      significant differences for sociodemographic and oral characteristics. Namely, in
      the precarious group, a poor dental status was generally observed: more cavities
      (3.6 versus 2), more absent teeth not replaced (6.8 versus 3.5) and less treated
      teeth (1.9 versus 3.9)--p < 0.0001. Multivariate analysis showed that main risk
      factors of poor dental status were to be aged and to be a foreigner. CONCLUSION:
      This study stresses the importance of the dental care needs in a context of poor
      insurance refunding for the costs of dental treatments and the lack of structures
      able to provide dental care for patients living in difficult social condition.
      These findings question the organization of the dental care system in France.

PMID- 16902382
TI  - [Outbreak of cutaneous leishmaniasis in military population coming back from
      French Guiana].
AB  - BACKGROUND: An outbreak of cutaneous leishmaniasis occurred among 71 soldiers who
      had participated in various missions during a 4-month's period in French Guiana.
      The aims of this study were (i) to describe outbreak and (ii) to determine risk
      factors of cutaneous leishmaniasis. METHODS: All patients were hospitalised.
      Cutaneous lesions were biopsied and cultured for species identification.
      Individual information was collected by a physician or a nurse, using on a
      standardised, anonymous chart. Data were processed with EpiInfo 6.04 and SAS.
      RESULTS: Mean age of the 71 soldiers was about 25.9 years (19-37 years). Twelve
      soldiers presented 56 lesions due to Leishmania (Viannia) guyanensis (attack rate
      = 16.9 for 100). Among 56 lesions, 13 lesions were localized on the trunk,
      usually an unexposed body area. Logistic regression highlighted military
      exercises in the forest during a high risk period of leishmaniasis transmission
      (OR = 11.2; p < 0.01), and the young age (OR = 1.33; p = 0.04). Vector control
      measures were not statistically significant. CONCLUSION: Military authorities
      should restrict deep forest activities during periods of high risk transmission.
      Vector control measures are essential. Officers should motivate their soldiers
      and supervise vector control measures. As ecotourism is developing, tourists as
      well as workers staying in deep forest must be informed of the risk and about
      vector control measures.

PMID- 16902383
TI  - [Evaluation of clinical practices: methods of data collection and information
      sources?].
AB  - OBJECTIVE: The aim of our study is to present the methods used to observe
      clinical practices, to evaluate their advantages and limits, and to specify the
      context in which they are preformed. METHODS: We conducted a bibliographical
      search on MEDLINE using key words, completed by an offline search. We selected
      articles published in French or English between 1985 and 2003. RESULTS: Thirty
      articles, of which 3 were reviews, as well as an additional 5 reports and 9
      books, were selected. We distinguished direct or objective approaches to clinical
      practices as well as indirect or declarative approaches. We also noted whether
      the approach was individual with data collected from individual practitioners, or
      collective, with data coming from databases. Most methods of collecting data used
      medical records, often in the context of internal or external clinical audits or
      peer reviews. The other sources of data were self-administered questionnaires,
      written case simulations and simulated patients. Data was also extracted from
      previously existing databases: claims databases, registries and ad hoc databases.
      CONCLUSION: An objective individual approach insures the highest quality of
      information, but possible high costs can limit the use of this approach. It is
      necessary to continue researching the best means of collecting data on clinical
      practices, because of the obligation of each practitioner to evaluate individual
      clinical practices.

PMID- 16902384
TI  - [Quasi-experimental evaluation of a nutritional educational intervention among
      home support assistants for the elderly].
AB  - BACKGROUND: The French National Program on Nutrition and Health has defined two
      specific objectives targeting older persons: (i) to improve their status in
      calcium and vitamin D and (ii) to prevent undernutrition. Home help provides
      support in activities of daily living, including meals, to dependent persons. The
      objective of our study was to evaluate the impact of a nutritional education
      intervention on knowledge and practices among home support assistants for the
      elderly. METHODS: Three facilities providing home support in Gironde (France)
      selected 132 home support assistants to follow an education program and 134
      controls. Nutrition training was conducted in the intervention group by a
      dietician during two half-day sessions in May-June 2004. A non randomized
      controlled trial design was used for evaluation. Nutritional knowledge (20
      questions) and practice (5 questions) of home support assistants were assessed by
      questionnaire before (April 2004) and after (September 2004) the training period
      in each group. Satisfaction of the intervention group was also assessed. RESULTS:
      The intervention group included 101 participants and the control group 106
      persons who answered both questionnaires before and after the education program.
      The intervention group was significantly younger (p < 0.05), less educated (p =
      0.01) and had less often participated to previous nutrition training (p < 0.001)
      than the control group. There was no significant difference between the two
      groups before intervention for their mean scores of knowledge or practices. The
      intervention group significantly improved its knowledge score (mean gain 2.5
      points, p < 0.001) after the training period, whereas the score remained
      unchanged in the control group (mean gain 0.5 points, p = 0.06). The impact of
      the nutritional education was very significant (p < 0.0001) after adjustment for
      the characteristics which differed between the two groups. The practice scores
      did not differ significantly after intervention in multivariate analyses.
      Satisfaction of trained home support assistants was very high. CONCLUSION: An
      education program of home support assistants for elderly persons can improve
      their nutritional knowledge, but this study cannot conclude that the intervention
      was efficient to improve the nutritional status of older persons.

PMID- 16902385
TI  - [The French version of the Leymann's questionnaire on workplace bullying: the
      Leymann Inventory of Psychological Terror (LIPT)].
AB  - BACKGROUND: Workplace bullying is considered as a major job stress factor and is
      associated with mental disorders. To date, there was no validated French version
      of the "Leymann Inventory of Psychological Terror" (LIPT), considered to be the
      instrument of reference. The objective of this study was to elaborate this French
      version and to explore its factorial, convergent and predictive validity.
      METHODS: The present study was based on a large sample of men and women of the
      working population asked to participate to a cross-sectional survey by a network
      of 143 occupational physicians in the South-East of France. This study included
      7694 subjects, 3132 men and 4562 women, who responded to the anonymous self
      questionnaire including the French version of the LIPT. This version was obtained
      by a standard forward/backward translation procedure. RESULTS: The LIPT allows to
      evaluate the 12-month prevalence of exposure to 45 forms of bullying. The
      analysis of an open question asking for other potentially missing forms of
      bullying underlined the satisfactory coverage of the LIPT. The study of the
      factorial validity showed a satisfactory coherence in the interpretation of the
      factors obtained. Leymann defined workplace bullying by the exposure to at least
      one form of bullying, weekly or more, and for at least six months. The convergent
      and predictive validity were increased when this definition was combined with the
      self-report of being exposed to bullying. CONCLUSION: This study is the first one
      elaborating and validating the French version of the LIPT by Leymann. This step
      of development and validation of the French version of questionnaires seems
      crucial to set up future high-quality studies, and to allow comparisons at the
      international level. Workplace bullying seems to be a serious problem in the
      French working life given the prevalence observed here (around 10%). Forthcoming
      studies should prefer using such validated questionnaire to better understand and
      prevent this occupational risk factor.

PMID- 16902386
TI  - Internet uses for health information seeking: A literature review.
AB  - BACKGROUND: With the widespread dissemination of the Internet throughout the
      world of health, it would be relevant to report on current knowledge about health
      information search on the Internet from the consumers' standpoint. METHODS: We
      conducted a bibliographical research over the past five years and distinguished
      between international and French studies. RESULTS: For a long time, the (mostly
      US) studies have been merely descriptive. The studies highlight that the factors
      associated with health searches on the Internet are similar to the factors
      underlying the digital divide. Consumer searches are deemed efficient although
      search skills are comparatively below standard. Attempts are underway to set up
      tools, circulate them widely, and ensure better quality information on the
      Internet. However, comprehension and literacy are still issues in some social
      groups. Regarding the impact on consumer health per se, a (positive) effect of
      the Internet seems to emerge but research should be continued. CONCLUSION: Many
      of the behaviors, uses or limits addressed in this paper pertain to any
      information search on the Internet but other problems or differences also occur
      in the specific area of health. Longitudinal investigations are needed,
      specifically to gain deeper insight into the impacts we have addressed, while
      rolling out a comprehensive approach to the temporal evolution of user practices
      and experiences. Specifically, the central issue is still to determine how (and
      for whom) the Internet alters information search behaviors and, in fine, to what
      extent this affects health behaviors and the recourse to healthcare.

PMID- 16902387
TI  - [Social responsibility of epidemiologists: a necessary debate. Contribution to
      the debate].

PMID- 16902388
TI  - [Prevalence of obesity in children (5-6 year-old) in Martinique (French West
      Indies) in 2003].

PMID- 16902389
TI  - [Drug delivery systems: a real therapeutic advance].
AB  - Established at the request of the Research Committee of the French National
      Academy of Pharmacy, this report on drug delivery systems (DDS) is a summary of
      information gathered by interviewing leaders in the pharmaceutical community and
      from the international literature. This report includes: a rapid recall of
      pharmaceutical formulations and changes over the last decades; a definition of
      DDS, indications on their evolution and a discussion on their contribution to
      drug administration; information on firms specialized in the elaboration of DDS,
      their interactions with the drug industry and the current and future market for
      DDS; a presentation of the potential offered by DDS for the drug industry; a
      discussion on technical, regulatory, and economic issues which could obstruct
      drug administration using a DDS; a description of certain DDS selected for their
      therapeutic contributions and a brief presentation of perspectives; a
      presentation of certain recommendations for organizations concerned with DDS.

PMID- 16902390
TI  - [New intelligent and targetted drug delivery systems. Pharmaceutical and
      biomedical applications].
AB  - Biomaterials are widely used in numerous medical applications. Chemical
      engineering has played a central role in this research and development. We review
      herein polymers as biomaterials, materials and approaches used in drug and
      protein delivery systems, materials used as scaffolds in tissue engineering, and
      nanotechnology and microfabrication techniques applied to biomaterials.

PMID- 16902391
TI  - [Multifactorial aspect of acute side effects of angiotensin converting enzyme
      inhibitors].
AB  - Angiotensin converting enzyme inhibitors are a class of drugs successfully used
      in the treatment of cardiovascular diseases. Despite their effectiveness,
      treatment with these drugs is characterized by chronic and acute side effects
      with variable expression depending on the clinical context. Angioedema occurs in
      patients with hypertension or heart failure. Anaphylactoid reaction is also
      reported in hemodialysis patients and severe hypotensive reaction in patients
      receiving transfused blood products and plasmapheresis. In this paper, we
      describe the role of kinins and metallopeptidases in the pathophysiology of these
      acute side effects. We also propose different experimental and clinical evidences
      which plead for an ecogenetic nature of these rare but life-threatening events.

PMID- 16902392
TI  - [New pyrimidine compounds with in vitro antimicrobial or antifungal activity].

PMID- 16902393
TI  - The Global HIV/AIDS pandemic, 2006.
AB  - Since the first cases of acquired immunodeficiency syndrome (AIDS) were reported
      in 1981, infection with human immunodeficiency virus (HIV) has grown to pandemic
      proportions, resulting in an estimated 65 million infections and 25 million
      deaths. During 2005 alone, an estimated 2.8 million persons died from AIDS, 4.1
      million were newly infected with HIV, and 38.6 million were living with HIV. HIV
      continues to disproportionately affect certain geographic regions (e.g., sub
      Saharan Africa and the Caribbean) and subpopulations (e.g., women in sub-Saharan
      Africa, men who have sex with men [MSM], injection-drug users [IDUs], and sex
      workers). Effective prevention and treatment of HIV infection with antiretroviral
      therapy (ART) are now available, even in countries with limited resources.
      Nonetheless, comprehensive programs are needed to reach all persons who require
      treatment and to prevent transmission of new infections.

PMID- 16902394
TI  - HIV prevalence among populations of men who have sex with men--Thailand, 2003 and
      2005.
AB  - In 2003 and 2005, the Thailand Ministry of Public Health-U.S. Centers for Disease
      Control and Prevention Collaboration and its partners conducted surveillance of
      human immunodeficiency virus (HIV) prevalence and risk factors among populations
      of men who have sex with men (MSM) in Thailand. In 2003, the assessment was
      conducted in Bangkok among a sample of MSM. In 2005, in addition to Bangkok, the
      assessment was conducted in Chiang Mai and Phuket provinces, and participants
      were categorized as MSM, male sex workers (MSW), or transgendered persons (TG).
      This report compares HIV prevalence among MSM in Bangkok during 2003 and 2005,
      reports HIV prevalence among the three populations in 2005, and summarizes the
      results of univariate and multivariate analysis of risk factors for HIV infection
      in 2005. The results indicated a significant increase in HIV infection among MSM
      in Bangkok from 2003 to 2005. The findings also indicated that in 2005, HIV
      infection was widespread among MSM, MSW, and TG in the three study locations.
      Moreover, the following risk factors were independently associated with HIV
      infection: being recruited from Bangkok or Chiang Mai (MSM), older age (MSM and
      TG), being recruited from a park or street location (MSW and TG), drug use (MSM),
      self-reporting a history of sexually transmitted infections (MSW), and self
      reporting a previous HIV-positive test result or refusing to disclose a previous
      HIV test result (MSM and MSW). Sex with women during the preceding 3 months was
      inversely associated with HIV prevalence among MSW. More effective behavioral and
      biomedical interventions for MSM, MSW, and TG are needed to stop the spread of
      HIV in these populations.

PMID- 16902395
TI  - HIV counseling, testing, and care of tuberculosis patients at chest clinics-
      Guyana, 2005-2006.
AB  - Tuberculosis (TB) is a leading cause of morbidity and mortality among persons
      living with human immunodeficiency virus (HIV) or acquired immunodeficiency
      syndrome (AIDS). During 2004, Guyana had an estimated TB incidence rate of 140
      per 100,000 population, the fourth highest rate in the Americas (after Haiti,
      Bolivia, and Peru); Guyana also had an estimated adult HIV prevalence of 2.5%,
      and 20% of TB patients were reported to be infected with HIV. In 2000, the Guyana
      Ministry of Health (MOH) began providing HIV counseling, testing, and referrals
      to HIV/AIDS programs at its six public chest clinics. At the end of 2005, chest
      clinics also began providing co-trimoxazole preventive therapy (CPT) to HIV
      infected TB patients as a measure against common opportunistic infections. During
      February-June 2006, an international team assessed the extent to which MOH chest
      clinics in Guyana had implemented these interventions during July 2005-June 2006.
      This report summarizes the results of that assessment, which determined that,
      among 253 TB patients sampled, 174 (69%) initially did not know their HIV
      infection status; 127 (73%) of those patients were offered HIV counseling and
      testing, and 115 (91%) accepted and were tested for HIV. Of the 115 who were
      tested, 11 (10%) were determined to be HIV infected; overall, 68 (35%) of the 194
      patients whose HIV-infection status was known were HIV infected (i.e., 11 who
      were tested at the chest clinics plus 57 with preexisting knowledge of their HIV
      status). These results indicate both a high rate of HIV infection among TB
      patients in Guyana and the ability of chest clinics to provide HIV-related
      interventions in resource-limited settings.

PMID- 16902396
TI  - Trends in HIV-related risk behaviors among high school students--United States,
      1991-2005.
AB  - Young persons who engage in unprotected sexual intercourse or use injection drugs
      are at increased risk for human immunodeficiency virus (HIV) infection. To
      examine changes in HIV-related risk behavior among high school students in the
      United States during 1991-2005, CDC analyzed data from eight national Youth Risk
      Behavior Surveys (YRBS) conducted during that period. This report summarizes the
      results of that analysis, which indicated that, during 1991-2005, the percentage
      of U.S. high school students engaging in HIV-related sexual risk behaviors
      decreased. During 1995-2005, the percentage of U.S. high school students who ever
      injected drugs remained less than 4%. However, many students still engage in HIV
      related risk behaviors. Measures aimed at changing these behaviors should be
      strengthened to decrease the incidence and prevalence of HIV/AIDS among young
      persons and meet the national 2010 objective for adolescent sexual behavior
      (objective 25-11).

PMID- 16902397
TI  - Vibrio parahaemolyticus infections associated with consumption of raw shellfish-
      three states, 2006.
AB  - During May 20-July 31, 2006, New York City, New York state, Oregon, and
      Washington health departments reported a total of 177 cases of Vibrio
      parahaemolyticus infection, of which 122 have been associated with 17 clusters. A
      cluster has been defined as a group of two or more ill persons who were linked to
      the same shellfish source (e.g., shared a meal at the same restaurant or obtained
      shellfish from the same seafood market). Certain clusters were associated with
      restaurants, certain clusters with seafood markets, and certain clusters with
      recreational harvesting. Three patients were hospitalized; no fatalities have
      been reported. No demographic (e.g., age, sex, or race) or medical history (e.g.,
      predisposing conditions) information is yet available regarding affected persons.

PMID- 16902398
TI  - Prevention of rotavirus gastroenteritis among infants and children.
      Recommendations of the Advisory Committee on Immunization Practices (ACIP).
AB  - In February 2006, a live, oral, human-bovine reassortant rotavirus vaccine
      (RotaTeq) was licensed for use among U.S. infants. The Advisory Committee on
      Immunization Practices recommends routine vaccination of U.S. infants with 3
      doses of this rotavirus vaccine administered orally at ages 2, 4, and 6 months.
      The first dose should be administered between ages 6-12 weeks. Subsequent doses
      should be administered at 4-10 week intervals, and all 3 doses should be
      administered by age 32 weeks. Rotavirus vaccine can be co-administered with other
      childhood vaccines. Rotavirus vaccine is contraindicated for infants with a
      serious allergic reaction to any vaccine component or to a previous dose of
      vaccine.

PMID- 16902399
TI  - The positive feedback role of arachidonic acid in the platelet-derived growth
      factor-induced signaling in lens epithelial cells.
AB  - PURPOSE: Platelet-derived growth factor (PDGF)-stimulated cell proliferation has
      been associated with reactive oxygen species (ROS)-mediated redox signaling. This
      study examined the role of arachidonic acid (AA) in PDGF-stimulated ROS
      generation in human lens epithelial B3 cells (HLE B3). METHODS: PDGF (1 ng/ml)
      stimulated ROS generation was examined using dichlorofluorescein (DCFH)-activated
      fluorescence by laser confocal microscopy while AA (30-150 muM)-stimulated
      superoxide anion production was measured using lucigenin-amplified
      chemiluminescence in serum-starved HLE B3 cells. PDGF-stimulated AA release was
      quantified by cells prelabeled with (3)H-AA with and without the presence of
      cytosolic phospholipase A(2) (cPLA(2)) inhibitor (AACOCF(3)) and mitogen
      activated protein (MAP) kinases (MEK) inhibitor (U0126). Western blot analysis
      was used to characterize the activated MAP kinase components in cell lysates or
      protein kinase C (PKC) translocation in isolated cytosolic and membrane
      fractions. Specific inhibitors to various enzymes were used in the study,
      including GF109203X for pan protein kinase C (PKC), AACOCF3 for cytosolic
      phospholipase A2 (cPLA(2)), U0126 for MEK, and DPI for NADPH oxidase. Inhibitors
      for AA metabolism were also used to examine the role of AA in PDGF-stimulated ROS
      generation, including CDC and NDGA for pan lipoxygenase, AA861 for 5
      lipoxygenase, indomethacin for cycloxygenase, and ketoconazole for cytochrome
      p450. RESULTS: We found that PDGF-stimulated ROS was eradicated by inhibitors to
      MEK, cPLA(2), 5-lipoxygenase, NADPH oxidase, or PKC. PDGF-stimulated AA release
      depended on both active cPLA(2) and ERK1/2. Exogenous AA showed a concentration
      dependent ROS generation via NADPH oxidase activation that was insensitive to MEK
      inhibitor, but sensitive to PKC inhibitor, and could be attenuated by superoxide
      dismutase (SOD), mannitol, or DPI. This effect of AA was specific as other long
      chain fatty acids (leinoleic acid, stearic acid), or AA derivatives (eicosa-11Z,
      14Z, 17Z-trienoic acid (20:3) and eicosa-11Z, 14Z-dienoic acid (20:2)) were
      ineffective. Inhibitor to lipoxygenase, in particular the 5-isoform, but not
      cycloxygenase or cytochrome p450, could diminish AA-stimulated luminescence
      generation. Western blot analysis showed that AA-treated cells transiently
      activated ERK1/2 and JNK, but not p38, in a time- and dose-dependent manner that
      was similar to that of PDGF. Finally, PDGF-stimulated PKC translocation depended
      on AA release while AA-stimulated PKC translocation was eradicated by
      lipoxygenase inhibition. CONCLUSIONS: We conclude that PDGF signaling in HLE B3
      cells is mediated by AA and its lipoxygenase metabolites, which provide a
      positive feedback loop for PDGF action, as AA and its metabolites can mobilize
      PKC and other factors needed for NADPH oxidase assembly and activation for ROS
      generation to facilitate cell proliferation. We further propose the role of AA in
      PDGF signaling.

PMID- 16902400
TI  - Optimized bacterial expression of myocilin proteins and functional comparison of
      bacterial and eukaryotic myocilins.
AB  - PURPOSE: To maximize the expression level of myocilin and its truncated proteins
      in Escherichia coli (E. coli) and to examine the biological effects of
      bacterially expressed myocilin as compared to eukaryotic myocilin on cultured
      human trabecular meshwork (TM) cells. METHODS: Myocilin full length (1-504 amino
      acids) and two truncated proteins, myocilin 1-270 and 271-504, were expressed and
      purified from an E. coli strain, Rosetta2(DE3)pLysS. The eukaryotic myocilin was
      purified from cultured medium of a transformed TM cell line (TM5) transduced with
      feline immunodeficiency virus that contains an internal cassette expressing full
      length myocilin. The morphology and adhesion of human TM cells plated either on
      fibronectin alone or on fibronectin/purified myocilin mixtures were assessed by
      phase contrast microscopy. Actin cytoskeleton was examined using Oregon Green
      phalloidin. Immunofluorescence staining for paxillin was also performed. RESULTS:
      The expression of full length and truncated myocilin proteins in
      Rosetta2(DE3)pLysS was markedly increased especially when the bacteria were grown
      in media supplemented with 1.0% glucose. Cell adhesion was impaired and
      microspikes were formed when TM cells were plated onto fibronectin/bacterial full
      length myocilin mixtures. Loss of actin stress fibers and focal adhesions was
      also observed. This myocilin phenotype was also seen with myocilin 1-270, but not
      with myocilin 271-504. The eukaryotic full length myocilin produced nearly
      identical de-adhesive effects as those of the bacterially expressed myocilin.
      CONCLUSIONS: The condition for a high level expression of full length and
      truncated myocilins in E. coli was optimized. The bacterial and eukaryotic
      recombinant full length myocilin produced similar biological consequence on TM
      cells. The myocilin phenotype appears to be largely due to the NH(2)-terminal
      half of the protein.

PMID- 16902401
TI  - Gene transfer of Smad7 modulates injury-induced conjunctival wound healing in
      mice.
AB  - PURPOSE: Smad7 is a molecule that blocks the Smad2/3 signal. Herein, we examined
      the effects of Smad7 gene introduction on post-injury conjunctival wound healing
      in mice. Its effects on the cultured human subconjunctival fibroblasts (SCFs)
      were also investigated. METHODS: A circumferential incision was made in the
      equatorial conjunctiva by using scissors in the right eye of fully anesthetized
      adult C57BL/6 mice (n=72). Smad7 cDNA-expressing adenoviral vector was topically
      applied. The control eye received nonfunctioning adenoviral vector. After 2, 5,
      7, and 30 days the eyes were processed for histological or immunohistochemical
      examination to evaluate wound healing of conjunctiva. The expressions of type-I
      collagen and growth factors were evaluated by real time-reverse transcriptase
      polymerase chain reaction. The effects of Smad7 gene introduction on the cultured
      human SCFs were also studied. RESULTS: Marked Smad7 protein expression was
      detected in the vector-treated conjunctival epithelium and fibroblasts that
      coincided with green fluorescein protein expression, whereas faint endogenous
      Smad7 expression was observed in the control tissue. In vivo Smad7 gene
      introduction blocked Smad2/3 nuclear translocation with suppression of alpha
      smooth muscle actin (alphaSMA) and vascular endothelial growth factor (VEGF) in
      fibroblasts and invasion of macrophages. Smad7 gene transfer suppressed mRNA
      expressions of connective tissue growth factor (CTGF), VEGF, and monocyte
      chemoattractant protein-1 in vivo and those of type-I collagen, alphaSMA, and
      CTGF in vitro. CONCLUSIONS: Smad7 gene transfer modulates injury-induced wound
      healing of conjunctival tissue in mice, suggesting that this strategy may be
      effective in preventing excessive scarring following filtration surgery. The
      mechanism might include suppression of activation of fibroblasts and reduction of
      macrophage invasion.

PMID- 16902402
TI  - The association of single nucleotide polymorphisms in the 5'-regulatory region of
      the lumican gene with susceptibility to high myopia in Taiwan.
AB  - PURPOSE: To study the relationships between single nucleotide polymorphisms
      (SNPs) of lumican, decorin, and DSPG3 genes and high myopia. METHODS: One hundred
      and twenty adult patients with high myopia (< -10.0 D) and 137 controls were used
      to study the relationships between the decorin, lumican, and DSPG genes and high
      myopia. All subjects were free of ocular diseases, other than myopia, as well as
      of other systemic genetic diseases. Genotyping was performed by direct sequencing
      after PCR amplification of chromosomal DNA. Allele frequencies were tested for
      Hardy-Weinberg disequilibrium. The chi(2) or Fisher test was conducted to
      investigate the genotypic and allelic distribution between the high myopia and
      control groups. RESULTS: The genotyping success rate was 100%. Univariate
      analysis revealed significant differences between patients and control subjects
      with respect to one of the SNPs (rs3759223, C->T) of the lumican gene, with a p
      value of 0.000283. There was no significant relationship between other SNPs of
      lumican, decorin, and DSPG genes and high myopia. CONCLUSIONS: Our results
      indicate that an SNP (rs3759223), which is located in the promoter region of the
      lumican gene, may be worth further investigation to determine its association
      with development of high myopia.

PMID- 16902403
TI  - Post-transfer editing mechanism of a D-aminoacyl-tRNA deacylase-like domain in
      threonyl-tRNA synthetase from archaea.
AB  - To ensure a high fidelity during translation, threonyl-tRNA synthetases (ThrRSs)
      harbor an editing domain that removes noncognate L-serine attached to tRNAThr.
      Most archaeal ThrRSs possess a unique editing domain structurally similar to D
      aminoacyl-tRNA deacylases (DTDs) found in eubacteria and eukaryotes that
      specifically removes D-amino acids attached to tRNA. Here, we provide mechanistic
      insights into the removal of noncognate L-serine from tRNAThr by a DTD-like
      editing module from Pyrococcus abyssi ThrRS (Pab-NTD). High-resolution crystal
      structures of Pab-NTD with pre- and post-transfer substrate analogs and with L
      serine show mutually nonoverlapping binding sites for the seryl moiety. Although
      the pre-transfer editing is excluded, the analysis reveals the importance of main
      chain atoms in proper positioning of the post-transfer substrate for its
      hydrolysis. A single residue has been shown to play a pivotal role in the
      inversion of enantioselectivity both in Pab-NTD and DTD. The study identifies an
      enantioselectivity checkpoint that filters opposite chiral molecules and thus
      provides a fascinating example of how nature has subtly engineered this domain
      for the selection of chiral molecules during translation.

PMID- 16902404
TI  - Kir6.2 mutations causing neonatal diabetes prevent endocytosis of ATP-sensitive
      potassium channels.
AB  - ATP-sensitive potassium (KATP) channels couple the metabolic status of a cell to
      its membrane potential-a property that endows pancreatic beta-cells with the
      ability to regulate insulin secretion in accordance with changes in blood
      glucose. The channel comprises four subunits each of Kir6.2 and the sulphonylurea
      receptor (SUR1). Here, we report that KATP channels undergo rapid internalisation
      from the plasma membrane by clathrin-mediated endocytosis. We present several
      lines of evidence to demonstrate that endocytosis is mediated by a tyrosine based
      signal (330YSKF333) located in the carboxy-terminus of Kir6.2 and that SUR1 has
      no direct role. We show that genetic mutations, Y330C and F333I, which cause
      permanent neonatal diabetes mellitus, disrupt this motif and abrogate endocytosis
      of reconstituted mutant channels. The resultant increase in the surface density
      of KATP channels would predispose beta-cells to hyperpolarise and may account for
      reduced insulin secretion in these patients. The data imply that endocytosis of
      KATP channels plays a crucial role in the (patho)-physiology of insulin
      secretion.

PMID- 16902405
TI  - Membrane targeting and activation of the Lowe syndrome protein OCRL1 by rab
      GTPases.
AB  - The X-linked disorder oculocerebrorenal syndrome of Lowe is caused by mutation of
      the OCRL1 protein, an inositol polyphosphate 5-phosphatase. OCRL1 is localised to
      the Golgi apparatus and early endosomes, and can translocate to lamellipodia upon
      growth factor stimulation. We show here that OCRL1 interacts with several members
      of the rab family of small GTPases. Strongest interaction is seen with Golgi
      associated rab1 and rab6 and endosomal rab5. Point mutants defective in rab
      binding fail to target to the Golgi apparatus and endosomes, strongly suggesting
      rab interaction is required for targeting of OCRL1 to these compartments.
      Membrane recruitment via rab binding is required for changes in Golgi and
      endosomal dynamics induced by overexpression of catalytically inactive OCRL1. In
      vitro experiments demonstrate that rab5 and rab6 directly stimulate the 5
      phosphatase activity of OCRL1. We conclude that rabs play a dual role in
      regulation of OCRL1, firstly targeting it to the Golgi apparatus and endosomes,
      and secondly, directly stimulating the 5-phosphatase activity of OCRL1 after
      membrane recruitment.

PMID- 16902406
TI  - Functional cooperation between FACT and MCM helicase facilitates initiation of
      chromatin DNA replication.
AB  - Chromatin is suppressive in nature to cellular enzymes that metabolize DNA,
      mainly due to the inherent inaccessibility of the DNA template. Despite extensive
      understanding of the involvement of chromatin-modifying factors in transcription,
      roles of related activities in DNA replication remain largely elusive. Here, we
      show that the heterodimeric transcriptional elongation factor FACT (facilitates
      chromatin transcription) is functionally linked to DNA synthesis. Its involvement
      in DNA replication is partly mediated by the stable association with the
      replicative helicase complex, MCM, and further by the coexistence with MCM on
      replication origin. Furthermore, relying on its nucleosome-reorganizing activity,
      FACT can facilitate chromatin unwinding by the MCM complex, which is otherwise
      inert on the nucleosomal template. As a consequence, the physical and functional
      interaction between FACT and MCM is an important determinant in the proper
      initiation of DNA replication and S phase in vivo. Together, our findings
      identify FACT as an integral and conserved component of the endogenous
      replication machinery, and support a model in which the concerted action of
      helicase and chromatin-modifying activities promotes chromosome replication.

PMID- 16902407
TI  - BIGPETALp, a bHLH transcription factor is involved in the control of Arabidopsis
      petal size.
AB  - In Arabidopsis, APETALA1, PISTILLATA, APETALA3 and SEPALLATA interact to form
      multimeric protein complexes required to specify petal identity. However, the
      downstream events that lead to petal specific shape and size remain largely
      unknown. Organ final size can be influenced by cell number or cell expansion or
      both. To date, no gene that specifically limits petal size by controlling
      postmitotic cell expansion has been identified. Here we have identified a novel
      petal-expressed, basic helix-loop-helix encoding gene (BIGPETAL, BPE) that is
      involved in the control of petal size. BPE is expressed via two mRNAs derived
      from an alternative splicing event. The BPEub transcript is expressed
      ubiquitously, whereas the BPEp transcript is preferentially expressed in petals.
      We demonstrate that BPEp is positively regulated downstream of APETALA3,
      PISTILLATA, APETALA1 and PISTILLATA3 and is negatively regulated downstream of
      AGAMOUS. Plants that lack the petal-expressed variant BPEp have larger petals as
      a result of increased cell size, showing that BPEp interferes with postmitotic
      cell expansion. BPEp is therefore a part of the network that links the patterning
      genes to final morphogenesis.

PMID- 16902408
TI  - A structural basis for Mg2+ homeostasis and the CorA translocation cycle.
AB  - We describe the CorA Mg(2+) transporter homologue from Thermotoga maritima in
      complex with 12 divalent cations at 3.7 A resolution. One metal is found near the
      universally conserved GMN motif, apparently stabilized within the transmembrane
      region. This portion of the selectivity filter might discriminate between the
      size and preferred coordination geometry of hydrated substrates. CorA may further
      achieve specificity by requiring the sequential dehydration of substrates along
      the length of its approximately 55 A long pore. Ten metal sites identified within
      the cytoplasmic funnel domain are linked to long extensions of the pore helices
      and regulate the transport status of CorA. We have characterized this region as
      an intrinsic divalent cation sensor and provide evidence that it functions as a
      Mg(2+)-specific homeostatic molecular switch. A proteolytic protection assay,
      biophysical data, and comparison to a soluble domain structure from Archaeoglobus
      fulgidus have revealed the potential reaction coordinate for this diverse family
      of transport proteins.

PMID- 16902409
TI  - 14-3-3sigma is a p37 AUF1-binding protein that facilitates AUF1 transport and AU
      rich mRNA decay.
AB  - Short-lived cytokine mRNAs contain an AU-rich destabilizing element (ARE). AUF1
      proteins bind the ARE, undergo shuttling, and promote cytoplasmic ARE-mRNA decay
      through a poorly understood mechanism. We therefore identified AUF1-interacting
      proteins that may play a role in ARE-mRNA decay. We used mass-spectrometry to
      identify 14-3-3sigma protein as an AUF1-interacting protein. 14-3-3sigma binds
      selectively and strongly to p37 AUF1 and to a lesser extent to the p40 isoform,
      the two isoforms most strongly associated with ARE-mRNA decay, but not to the two
      larger isoforms, p42 and p45. The 14-3-3sigma interaction site on p37 was mapped
      to a region found only in the two smaller AUF1 isoforms and which overlaps a
      putative nuclear localization signal (NLS). Stable overexpression of 14-3-3sigma
      significantly increased cytoplasmic accumulation of p37 AUF1 and reduced the
      steady-state level and half-life of a reporter ARE-mRNA. siRNA silencing of AUF1
      eliminated the effect of 14-3-3sigma overexpression. 14-3-3sigma therefore binds
      to p37 AUF1, retains it in the cytoplasm probably by masking its NLS, and
      enhances rapid turnover of ARE-mRNAs.

PMID- 16902410
TI  - IKKalpha controls p52/RelB at the skp2 gene promoter to regulate G1- to S-phase
      progression.
AB  - The IkappaB-inducing kinase (IKK) is composed of two catalytic subunits, IKKalpha
      and IKKbeta, and a regulatory subunit, IKKgamma. IKK-regulated signaling pathways
      are believed to promote the proliferation of normal cells as well as the aberrant
      proliferation of cancer cells. The molecular mechanisms linking the IKK signaling
      pathway components to the cell cycle machinery are not entirely understood. To
      study the function(s) of the catalytic subunits of the IKK complex, we used
      pancreatic cancer cells, with constitutive IKK activity. We show that the G1
      phase of the cell cycle is specifically regulated by the IKKalpha subunit, which
      regulates the stability of the cyclin-dependent kinase inhibitor p27(Kip1).
      Increased p27(Kip1) protein levels following the transfection of IKKalpha
      specific siRNAs are a result of the downregulation of the F-box protein S-phase
      kinase-associated protein 2 (skp2). Additionally, we demonstrate that IKKalpha
      signaling regulates the transcription of the skp2 gene by controlling the
      composition of a RelB-containing NF-kappaB complex. Together, this work defines a
      novel IKKalpha-regulated growth pathway involving the p52/RelB-dependent
      transcriptional regulation of the skp2 gene.

PMID- 16902411
TI  - Dissecting docking and tethering of secretory vesicles at the target membrane.
AB  - Secretory vesicles dock at their target in preparation for fusion. Using single
      vesicle total internal reflection fluorescence microscopy in chromaffin cells, we
      show that most approaching vesicles dock only transiently, but that some are
      captured by at least two different tethering modes, weak and strong. Both vesicle
      delivery and tethering depend on Munc18-1, a known docking factor. By decreasing
      the amount of cortical actin by Latrunculin A application, morphological docking
      can be restored artificially in docking-deficient munc18-1 null cells, but
      neither strong tethering nor fusion, demonstrating that morphological docking is
      not sufficient for secretion. Deletion of the t-SNARE and Munc18-1 binding
      partner syntaxin, but not the v-SNARE synaptobrevin/VAMP, also reduces strong
      tethering and fusion. We conclude that docking vesicles either undock immediately
      or are captured by minimal tethering machinery and converted in a munc18
      1/syntaxin-dependent, strongly tethered, fusion-competent state.

PMID- 16902412
TI  - Hypertrophic growth in cardiac myocytes is mediated by Myc through a Cyclin D2
      dependent pathway.
AB  - c-Myc (Myc) is highly expressed in developing embryos where it regulates body
      size by controlling proliferation but not cell size. However, Myc is also induced
      in many postmitotic tissues, including adult myocardium, in response to stress
      where the predominant form of growth is an increase in cell size (hypertrophy)
      and not number. The function of Myc induction in this setting is unproven.
      Therefore, to explore Myc's role in hypertrophic growth, we created mice where
      Myc can be inducibly inactivated, specifically in adult myocardium. Myc-deficient
      hearts demonstrated attenuated stress-induced hypertrophic growth, secondary to a
      reduction in cell growth of individual myocytes. To explore the dependence of Myc
      induced cell growth on CycD2, we created bigenic mice where Myc can be
      selectively activated in CycD2-null adult myocardium. Myc-dependent hypertrophic
      growth and cell cycle reentry is blocked in CycD2-deficient hearts. However, in
      contrast to Myc-induced DNA synthesis, hypertrophic growth is independent of
      CycD2-induced Cdk2 activity. These data suggest that Myc is required for a normal
      hypertrophic response and that its growth-promoting effects are also mediated
      through a CycD2-dependent pathway.

PMID- 16902414
TI  - No evidence for maternal-fetal microchimerism in infantile hemangioma: a
      molecular genetic investigation.
AB  - In this study, using the placental origin theory as a basis, we set out to
      explore whether hemangioma endothelial cells (HEC) were maternal in origin. We
      rigorously addressed this hypothesis using several molecular genetic techniques.
      Fluorescent in situ hybridization on surgical specimens of proliferating
      hemangiomas (n=8) demonstrated no XX-labeled HEC from resected tumors of male
      infants. This analysis was followed by PCR genotyping of HEC (n=11) using
      microsatellite markers where cellular components were genotyped and compared to
      genomic DNA of corresponding mother-child pairs. In the seven informative mother
      child pairs, HEC matched the genotype of the child and not the maternal genotype.
      Concerned that HEC represented a mixed population of cells, we subsequently
      enriched for cells using the placental-specific endothelial cell (EC) marker, Fc
      gammaRII. Three informative mother-child pairs exhibited only the genotype of the
      child in our enriched cell population. Using sequence analysis, we identified an
      informative single nucleotide polymorphism in an exon of the placental-EC
      specific protein, GLUT1. When comparing GLUT1 complementary DNA (cDNA) with
      mother-child DNA, the genotype of the cDNA matched the constitutional DNA of the
      child. Our results indicate that hemangiomas are not microchimeric in origin.
      This study provides further insight into the origin of a tumor whose pathogenesis
      remains elusive.

PMID- 16902413
TI  - Nebulin regulates thin filament length, contractility, and Z-disk structure in
      vivo.
AB  - The precise assembly of the highly organized filament systems found in muscle is
      critically important for its function. It has been hypothesized that nebulin, a
      giant filamentous protein extending along the entire length of the thin filament,
      provides a blueprint for muscle thin filament assembly. To test this hypothesis,
      we generated a KO mouse model to investigate nebulin functions in vivo. Nebulin
      KO mice assemble thin filaments of reduced lengths and approximately 15% of their
      Z-disks are abnormally wide. Our data demonstrate that nebulin functions in vivo
      as a molecular ruler by specifying pointed- and barbed-end thin filament capping.
      Consistent with the shorter thin filament length of nebulin deficient mice,
      maximal active tension was significantly reduced in KO animals. Phenotypically,
      the murine model recapitulates human nemaline myopathy (NM), that is, the
      formation of nemaline rods combined with severe skeletal muscle weakness. The
      myopathic changes in the nebulin KO model include depressed contractility, loss
      of myopalladin from the Z-disk, and dysregulation of genes involved in calcium
      homeostasis and glycogen metabolism; features potentially relevant for
      understanding human NM.

PMID- 16902415
TI  - Loss of the acyl-CoA binding protein (Acbp) results in fatty acid metabolism
      abnormalities in mouse hair and skin.
AB  - Proper fatty acid metabolism is critical for hair and skin development and
      maintenance. The acyl-CoA binding protein (Acbp) is a widely expressed protein
      that binds long-chain fatty acyl-CoA esters and plays a role in fatty acyl-CoA
      transport and pool formation. However, loss of function of Acbp in the whole
      animal has not been investigated. Here, we show that deletion of Acbp in mouse
      results in sebocyte hyperplasia and sparse, matted hair with a greasy appearance.
      Consistent with these gross abnormalities, Acbp is highly expressed in the
      pilosebaceous units of mouse skin as determined by Northern analysis and in situ
      hybridization. Loss of Acbp also results in fatty acid metabolism abnormalities,
      with hair lipid profiles showing altered levels of triacylglycerols and nearly co
      migrating lipids. These data suggest that Acbp plays a role in triacylglycerol
      biosynthesis, and that regulation of this process is important for proper hair
      and skin development and maintenance in the mouse.

PMID- 16902416
TI  - Delphinidin, an anthocyanidin in pigmented fruits and vegetables, protects human
      HaCaT keratinocytes and mouse skin against UVB-mediated oxidative stress and
      apoptosis.
AB  - Solar UV radiation, in particular its UVB component, is the primary cause of many
      adverse biological effects, the most damaging of which is skin cancer. Here, we
      assessed the photochemopreventive effect of delphinidin, a major anthocyanidin
      present in many pigmented fruits and vegetables, on UVB-mediated responses in
      human immortalized HaCaT keratinocytes and SKH-1 hairless mouse skin. We found
      that pretreatment of cells with delphinidin (1-20 microM for 24 hours) protected
      against UVB (15-30 mJ/cm2, 24 hours)-mediated (i) decrease in cell viability and
      (ii) induction of apoptosis. Furthermore, we found that pretreatment of HaCaT
      cells with delphinidin inhibited UVB-mediated (i) increase in lipid peroxidation;
      (ii) formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG); (iii) decrease in
      proliferating cell nuclear antigen expression; (iv) increase in poly(ADP-ribose)
      polymerase cleavage; (v) activation of caspases; (vi) increase in Bax; (vii)
      decrease in Bcl-2; (viii) upregulation of Bid and Bak; and (ix) downregulation of
      Bcl-xL. Topical application of delphinidin (1 mg/0.1 ml DMSO/mouse) to SKH-1
      hairless mouse skin inhibited UVB-mediated apoptosis and markers of DNA damage
      such as cyclobutane pyrimidine dimers and 8-OHdG. Taken together our results
      suggest that treatment of HaCaT cells and mouse skin with delphinidin inhibited
      UVB-mediated oxidative stress and reduced DNA damage, thereby protecting the
      cells from UVB-induced apoptosis.

PMID- 16902417
TI  - Surface coatings determine cytotoxicity and irritation potential of quantum dot
      nanoparticles in epidermal keratinocytes.
AB  - Quantum dot (QD) nanoparticles have potential applications in nanomedicine as
      drug delivery vectors and diagnostic agents, but the skin toxicity and irritation
      potential of QDs are unknown. Human epidermal keratinocytes (HEKs) were used to
      assess if QDs with different surface coatings would cause differential effects on
      HEK cytotoxicity, proinflammatory cytokine release, and cellular uptake.
      Commercially available QDs of two different sizes, QD 565 and QD 655, with
      neutral (polyethylene glycol (PEG)), cationic (PEG-amine), or anionic (carboxylic
      acid) coatings were utilized. Live cell imaging and transmission electron
      microscopy were used to determine that all QDs localized intracellularly by 24
      hours, with evidence of QD localization in the nucleus. Cytotoxicity and release
      of the proinflammatory cytokines IL-1beta, IL-6, IL-8, IL-10, and tumor necrosis
      factor-alpha were assessed at 24 and 48 hours. Cytotoxicity was observed for QD
      565 and QD 655 coated with carboxylic acids or PEG-amine by 48 hours, with little
      cytotoxicity observed for PEG-coated QDs. Only carboxylic acid-coated QDs
      significantly increased release of IL-1beta, IL-6, and IL-8. These data indicate
      that QD surface coating is a primary determinant of cytotoxicity and
      immunotoxicity in HEKs, which is consistent across size. However, uptake of QDs
      by HEKs is independent of surface coating.

PMID- 16902418
TI  - Population-based assessment of non-melanoma cancer risk in relatives of cutaneous
      melanoma probands.
AB  - Using the unique Utah Population Database, which links Utah genealogical data
      with Utah cancer data, we examined risks for other cancers among relatives of
      4,079 melanoma cases. Age- and sex-specific rates for 35 different cancer sites
      were calculated, and used to estimate relative risks among relatives. In addition
      to the well-recognized risk for melanoma among first-degree relatives, we found
      significantly increased risks for prostate, breast, and colon cancers, non
      Hodgkin's lymphoma, and multiple myeloma, ranging from 32 to 72% increased risk.
      Among second-degree relatives, in addition to increased risk for melanoma, we
      identified significantly increased risks for prostate cancer and multiple myeloma
      (27 and 53% increase, respectively). Among first-degree relatives of melanoma
      cases diagnosed before the age of 40 years, we found significantly elevated risks
      for cutaneous melanoma (380% increase) and prostate cancer (83% increase).
      Significantly increased risks for prostate cancer and multiple myeloma in both
      first- and second-degree relatives of melanoma cases are suggestive of heritable
      cancer syndromes. The increased risks for five additional cancer types in first
      degree relatives of melanoma cases suggest that individuals with a family history
      of melanoma should strictly adhere to recommended screenings for all cancers.

PMID- 16902420
TI  - DNase1L2 degrades nuclear DNA during corneocyte formation.
AB  - The removal of keratinocyte (KC) nuclear DNA by deoxyribonucleases (DNases) is an
      important step in the formation of normal stratum corneum (SC). However, the
      molecular identity of the DNA-degrading enzymes has so far remained elusive. Here
      we show that the endonuclease DNase1-like 2 (DNase1L2) is preferentially
      expressed in the epidermis and that its expression correlates with terminal
      differentiation of KC in vitro and in vivo. In biopsies of normal skin, DNase1L2
      mRNA was regularly found in suprabasal KC and DNase1L2 protein was highly
      abundant in the stratum granulosum. In contrast to normal skin, DNase1L2
      expression was downregulated in parakeratotic epidermis such as in psoriatic
      lesions. When DNase1L2 gene expression was knocked down by small interfering RNA
      in a human skin equivalent model, nuclei were maintained through all layers of
      the SC. Taken together, our data demonstrate that DNase1L2 plays an essential
      role in DNA degradation during terminal differentiation of epidermal KC.

PMID- 16902419
TI  - Diminished lymphocyte adhesion and alleviation of allergic responses by small
      molecule- or antibody-mediated inhibition of L-selectin functions.
AB  - Selectins are attractive targets for specific anti-inflammatory therapies. Using
      human lymphocytes as well as an L-selectin-transfected pre-B-cell line in dynamic
      flow chamber experiments, we could demonstrate that the small-molecule compound
      efomycine M blocks L-selectin-mediated lymphocyte rolling on sialylated Lewis(X),
      an action that was confirmed by plasmon resonance spectroscopy. Recruitment of
      naive lymphocytes to peripheral lymph nodes depends on L-selectin-mediated
      adhesion to high endothelial venules. We performed intravital microscopy studying
      lymphocyte rolling in peripheral lymph nodes and showed a 53% reduction
      (P=0.0006) of lymphocyte rolling in mice treated with efomycine M or a function
      blocking antibody against L-selectin. In addition, the number of lymph node
      homing T cells was reduced by >60% using either efomycine M or L-selectin
      blocking antibodies. As recruitment of naive lymphocytes is a prerequisite for
      sensitization in T-cell-mediated immune reactions and allergic responses, mice
      were treated with efomycine M or an L-selectin-specific antibody during contact
      sensitization with DNFB. After adoptive transfer of corresponding T cells into
      non-sensitized recipient mice, the capacity of these cells to induce contact
      hypersensitivity was significantly reduced (P=0.0002 and P=0.0001, respectively).
      Our data demonstrate that it is possible, in principle, to diminish T-cell
      mediated allergic reactions through interference with L-selectin functions during
      the early sensitization phase.

PMID- 16902421
TI  - Normal wound healing in mice deficient for fibulin-5, an elastin binding protein
      essential for dermal elastic fiber assembly.
AB  - Extracellular matrix proteins play a critical role in dermal wound healing by
      mediating matrix-cell interactions and re-establishing the dermal architecture
      and environment. Fibulin-5 is an elastin-binding protein essential for elastic
      fiber development in vivo, and it has recently been shown to inhibit angiogenesis
      in vitro. Here, we use mice deficient for the fibulin-5 gene (fbln5) to examine
      the role of fibulin-5 and the effect of the loss of elastic fibers in dermal
      wound healing. Fbln5 is upregulated in the granulation tissue 14 days after full
      thickness wounding in wild-type mice, before the formation of elastic fibers.
      Although wounded fbln5(-/-) skin showed enhanced neovascularization compared to
      the wild-type skin, no difference in the rate of wound closure was observed
      between mutant and wild-type mice. In addition, a breaking strength test revealed
      that there was no difference in breaking stress or strain between wild-type and
      fbln5(-/-) wounded skin. These results suggest that fibulin-5 and elastic fibers
      are not directly involved in short-term wound healing. Clearly, the long-term
      effect of the absence of fibulin-5 on the function and integrity of regenerated
      skin needs to be further addressed.

PMID- 16902422
TI  - Wavelength-dependent induction of CYP24A1-mRNA after UVB-triggered calcitriol
      synthesis in cultured human keratinocytes.
AB  - Earlier investigations in our laboratory have demonstrated that UVB irradiation
      of cultured human keratinocytes induces the conversion of 7-dehydrocholesterol (7
      DHC) to hormonally active 1alpha,25-dihydroxyvitamin D3 (calcitriol). In the
      research presented here, we have investigated the influence of UVB-triggered
      calcitriol production on gene expression of the vitamin D3 hydroxylating enzymes
      catabolic 25-hydroxyvitamin-D3-24-hydroxylase (CYP24A1), active vitamin-D3-25
      hydroxylase (CYP27A1), and 25-hydroxyvitamin-D3-1alpha-hydroxylase (CYP27B1)
      using real-time PCR. Our results demonstrate a marked and wavelength-dependent
      induction of CYP24A1-mRNA in cultured human keratinocytes supplemented with 7
      DHC, which parallels the spectral optimum at about 300 nm of calcitriol
      production as detected by HPLC and radioimmunoassay. Owing to the high
      sensitivity of real-time PCR, we provide evidence of a wavelength-dependent
      induction of CYP24A1-mRNA even in 7-DHC-deficient keratinocytes. Interestingly,
      we have found a strong but transient induction of CYP24A1-mRNA in non-irradiated
      keratinocytes, followed by accelerated cell proliferation. In contrast, UVB and
      calcitriol had no effect on gene expression of CYP27A1 and CYP27B1. We conclude
      from these experiments a constitutive gene expression of the vitamin D3
      hydroxylases, whereas the catabolic enzyme CYP24A1 is markedly regulated by UVB,
      calcitriol, and perhaps cell proliferation. If confirmed at protein level, these
      findings could have an impact on epidermal vitamin D3 metabolism and its
      modulation by UVB in health and disease.

PMID- 16902492
TI  - Relationship between optokinetic nystagmus response and recognition visual
      acuity.
AB  - PURPOSE: The aim of this study was to investigate the relation between
      recognition visual acuity (RVA) and optokinetic nystagmus (OKN) response
      exhibited to different bar sizes with varying contrast. METHODS: OKN testing was
      performed in 52 children aged between 3 and 11 years. The children were evaluated
      in two groups according to their RVA. Group I consisted of 22 eyes with RVA equal
      to or better than 0.1 logMAR units. Group II consisted of 30 eyes with RVA 0.2-1
      logMAR units. Each subject was seated 60 cm from the screen of Ophthimus device,
      and was exposed to consecutive black and white stripes of seven different spatial
      frequencies (0.08-1.6 cycle/degree). The narrowest bar that elicited OKN was
      identified, and then the OKN contrast threshold at this bar size was established.
      RESULTS: Twenty-one of the 22 eyes in Group I, and 26 of the 30 eyes in Group II
      exhibited 1.6 cycle/degree spatial frequency (P=0.287). In Group II, 88.9% of the
      18 eyes with RVA 0.2-0.5 logMAR responded at this maximum spatial frequency,
      whereas the corresponding figure for the 12 eyes with RVA 0.6-1 logMAR was 83.3%
      (P=0.531). Contrast sensitivity (CS) significantly changed with age in Group I
      (P=0.006). When the eyes that responded at maximum spatial frequency in the two
      groups were compared, the mean CS in Group II was significantly lower than that
      in Group I (P=0.005). CONCLUSIONS: The results indicate no relation between
      spatial frequency threshold for OKN response and RVA in children. However, the
      children with RVA deficits had significantly lower CS.

PMID- 16902423
TI  - ABCA12 is the major harlequin ichthyosis gene.
AB  - Harlequin ichthyosis (HI) is the most severe form of autosomal-recessive,
      congenital ichthyosis. Affected infants have markedly impaired barrier function
      and are more susceptible to infection. Abnormalities in the localization of
      epidermal lipids as well as abnormal lamellar granule formation are features of
      HI skin. Previously, we and others have shown that mutations in the ABCA12 gene
      encoding an adenosine triphosphate-binding cassette (ABC) transporter underlie
      the skin disease HI. In this study, we have sequenced the ABCA12 gene in an
      additional 14 patients and show that all contain mutations, with the majority
      being either nonsense substitution or frameshift mutations. Eleven HI patients
      had bi-allelic ABCA12 mutations, whereas in the remaining three HI patients in
      this study, ABCA12 mutations were detected on only one allele by sequencing. In
      addition, the one patient from the previous study where no sequence mutations
      were detected was screened for heterozygous deletions. A combination of
      oligonucleotide arrays, multiplex PCR analysis and single-nucleotide polymorphism
      genotyping revealed a heterozygous intragenic deletion in exon 8. These mutation
      data establish ABCA12 as the major HI gene.

PMID- 16902493
TI  - Intravitreal triamcinolone acetonide for macular oedema owing to retinal vein
      occlusion.
AB  - PURPOSE: To assess the long-term safety and efficacy of intravitreal
      triamcinolone acetonide injection in the management of macular oedema caused by
      central, hemi-, and branch retinal vein occlusion (CRVO, HRVO, or BRVO). METHODS:
      This prospective, interventional case series included 13 patients (13 eyes) with
      retinal vein occlusion and macular oedema. They received an intravitreal
      injection of 4 mg triamcinolone acetonide. Follow-up was for 1 year with repeat
      injections where appropriate. Outcome measures were visual acuity and macular
      thickness measured using ocular coherence tomography (OCT). RESULTS: There were
      four patients with CRVO, one with HRVO, and eight with BRVO (13 eyes). Mean
      duration of symptoms before intravitreal triamcinolone acetonide injection was
      6.8 months (SD 4.5 months). Eight eyes (62%) responded well with improved visual
      acuity and macular thickness 1-3 months postinjection. All eight eyes developed
      recurrent macular oedema and five received repeat injections. Three patients
      declined a second injection. No improvement in visual acuity or OCT macular
      thickness was seen after the second injection with visual acuity returning to
      baseline levels at 1-year follow-up. Three eyes (23%) showed no response to the
      initial injection (no improvement in macular thickness or visual acuity). Seven
      patients (54%) had a rise in intraocular pressure with six (46%) requiring
      treatment. CONCLUSIONS: Intravitreal injection of triamcinolone acetonide is
      effective as a short-term treatment of macular oedema owing to retinal vein
      occlusion, improving both visual acuity and macular thickness. However, this
      effectiveness is not maintained after 1 year despite repeat injections.

PMID- 16902494
TI  - ReGAE 2: glaucoma awareness and the primary eye-care service: some perceptions
      among African Caribbeans in Birmingham UK.
AB  - AIMS: Investigations into glaucoma awareness have drawn on informed, clinic-based
      populations. The paper reports a section of findings from a larger study that
      aimed to elicit the perceptions of those potentially less informed in community
      settings. METHODS: A qualitative investigation used face-to-face interviews and
      focus group discussions with 48 African Caribbean participants outside the
      hospital eye-service. Interview data were transcribed and coded using manual and
      computer-aided methods. Inferences and interpretations were corroborated by
      discussion with expert advisors and community members not directly involved in
      the study. RESULTS: Positive attitudes to health promotion existed, but 'eye
      health' did not appear to be integral to individuals' health schemas. The
      capacity for primary eye care to enhance glaucoma knowledge appeared under
      utilised and inconsistent across modes of service delivery and was undermined by
      perceived conflicts of interest. CONCLUSIONS: Enhancing reciprocal understanding
      between service users and ophthalmic practitioners in primary care is central to
      developing flexible, responsive local eye-care services. The study suggested
      useful foci for cultural self-reflection and self-awareness on the part of health
      professionals themselves, in relation to glaucoma detection. Areas for further
      research are identified.

PMID- 16902495
TI  - Ocular myopathy of Wegener's granulomatosis.

PMID- 16902496
TI  - Membrane-bound CD95 ligand expressed on human antigen-presenting cells prevents
      alloantigen-specific T cell response without impairment of viral and third-party
      T cell immunity.
AB  - Genetically modified antigen-presenting cells (APC) represent an attractive
      strategy for in vitro immunomodulation. In the human system, APC expressing HLA
      A1 and a membrane-bound form of CD95L (m-CD95L) were used for selective depletion
      of HLA-A1-specific T cells. In short-term assays, m-CD95L-expressing APC-induced
      apoptosis in activated T cells and the constitutive presence of m-CD95L and HLA
      A1 expressing APC in long-term T cell cultures prevented the expansion of CD4(+)
      and CD8(+) HLA-A1-specific T cells and the development of HLA-A1-specific
      cytotoxicity. However, immunity towards third party, viral and bacterial antigens
      was maintained and T cells spared from depletion could be induced to develop
      cytotoxicity towards unrelated antigens. Interestingly, inhibition of HLA-A1
      specific T cell response absolutely requires the coexpression of m-CD95L and HLA
      A1 antigen on the same APC. Thus, m-CD95L expressing APC might be used in
      clinical settings to obtain tolerance induction in allogeneic transplantation
      systems or autoimmune diseases.

PMID- 16902497
TI  - Surgery in elderly cancer patients.

PMID- 16902498
TI  - Treatment of high-risk, non-muscle-invasive bladder cancer.

PMID- 16902499
TI  - Penile rehabilitation after radical prostatectomy.

PMID- 16902512
TI  - Understanding the natural treated history of chronic prostatitis/chronic pelvic
      pain syndrome.

PMID- 16902511
TI  - Adjuvant bicalutamide for early prostate cancer: an update.

PMID- 16902513
TI  - Is nephron-sparing surgery for small renal masses underused?

PMID- 16902514
TI  - Long-term outcomes of the distal urethral polypropylene sling procedure for
      stress urinary incontinence.

PMID- 16902515
TI  - What good or harm comes from prophylactic antibiotics in children with
      vesicoureteral reflux?

PMID- 16902516
TI  - What is the prognostic impact of positive surgical margins in surgically treated
      prostate cancer?

PMID- 16902517
TI  - Saw palmetto for benign prostatic hyperplasia: just how effective is it?

PMID- 16902518
TI  - Finasteride as a chemopreventive agent in prostate cancer: impact of the PCPT on
      urologic practice.
AB  - Prostate cancer chemoprevention involves the use of natural and/or synthetic
      agents that inhibit or reverse the development of precancerous lesions or delay
      progression of these lesions to invasive disease. The recent completion of the
      first Phase III trial for prostate cancer prevention, the Prostate Cancer
      Prevention Trial (PCPT) using the drug finasteride, has provided the urologic
      community with the first evidence that a chemopreventive agent can reduce the
      risk of developing prostate cancer. The enthusiasm for the clear relative risk
      reduction in the finasteride arm of the trial has been tempered by the
      observation that the incidence of high-grade tumors was higher in men receiving
      finasteride compared to those on placebo. A question remains about whether the
      observed higher incidence in high-grade tumors is real or whether it is related
      to a pathologic or sampling artifact. The PCPT has instigated a great deal of
      debate, resulting in the larger urologic community being reluctant to recommend
      the widespread use of finasteride as a chemopreventive agent. This review
      summarizes the PCPT, analyzes its controversial results, and describes future
      prostate cancer chemoprevention studies.

PMID- 16902519
TI  - Mechanisms of disease: late-onset hypogonadism.
AB  - Late-onset hypogonadism (formerly called the andropause) is a clinical and
      biochemical syndrome associated with advancing age, which is characterized by
      typical signs and symptoms and a deficiency in serum testosterone levels. Age
      related hypoandrogenism in the male is a result of the interaction of
      hypothalamopituitary and testicular factors. The hypothalamic pulsatile secretion
      of gonadotropin-releasing hormone is blunted, due to increased hypothalamic
      sensitivity to inhibition by steroids, but the responsiveness of the pituitary
      gonadotrophs seems to be intact. In addition, testicular volume as well as Leydig
      cell mass and reserve function are diminished. Taken together, these mechanisms
      result in reduced testosterone secretion and the loss of nycthemeral variability.

PMID- 16902520
TI  - Primer: using decision analysis to improve clinical decision making in urology.
AB  - Many clinical decisions in urology involve uncertainty about the course of
      disease or the effectiveness of treatment. Many decisions also involve trade
      offs; for example, an improvement in patient survival at the cost of an increased
      risk of treatment-related adverse effects. Decision analysis is a formal,
      quantitative method for systematically comparing the benefits and harms of
      alternative clinical strategies under circumstances of uncertainty. The basic
      steps in performing a decision analysis are to define the clinical scenario or
      problem, identify the clinical strategies to be considered in the decision,
      enumerate all of the important sequelae of each strategy and their associated
      probabilities, define the outcome of interest, and assign a value to each
      possible outcome. Health outcomes can be defined in a number of ways, including
      quality-adjusted survival. A key aspect of decision analysis is allowing the
      values of particular health outcomes to vary from patient to patient, depending
      on individual preferences. Decision analysis has already been used to assess a
      variety of prevention, screening and treatment decisions in urology, and there is
      much potential for its future application. Greater incorporation of decision
      analytic techniques into urology research and clinical practice might improve
      decision making, and thereby improve patient outcomes.

PMID- 16902521
TI  - Discussing quality-of-life issues with a patient newly diagnosed with prostate
      cancer.
AB  - BACKGROUND: A 66-year-old man with hypertension, hyperlipidemia, and benign
      prostatic hyperplasia presented for evaluation of an elevated PSA level of 6.2
      ng/ml. INVESTIGATIONS: Transrectal ultrasound-guided 12-core prostate needle
      biopsy. DIAGNOSIS: Clinically localized, clinical stage T1c adenocarcinoma of the
      prostate. MANAGEMENT: Following a full discussion of the risks and benefits of
      his treatment options, including quality-of-life sequelae, the patient opted for
      radical prostatectomy.

PMID- 16902522
TI  - Teaching of removable prosthodontics in the UK.

PMID- 16902523
TI  - CASP and CONSORT.

PMID- 16902524
TI  - A bitter taste.

PMID- 16902525
TI  - Identifying deficiencies.

PMID- 16902526
TI  - Obliged to reply.

PMID- 16902527
TI  - Improve uptake of care.

PMID- 16902528
TI  - Fear of litigation.

PMID- 16902529
TI  - Puzzling options.

PMID- 16902543
TI  - Surgical guidelines for dental implant placement.
AB  - The goal of an implant supported reconstruction is to obtain optimal aesthetics
      and function. In order to achieve this, visualisation of the final restorative
      reconstruction is necessary prior to beginning treatment. The term 'restorative
      driven' treatment planning has been used to identify this process. It requires a
      team approach of specialists, who can develop a multi-disciplinary treatment
      plan. It starts with an accurate diagnosis, which will lead to a prognosis of
      each individual tooth and the overall dentition. This information will help the
      clinician develop the treatment options suitable for tooth replacement. Only when
      the goals have been defined can the sequence of therapy be established. Working
      backwards from the wax-up of the final diagnostic model of the proposed treatment
      assists not only with the management of the complex case, but will help avoid
      mishaps. Effective communication between the team and the patient is extremely
      important. Understanding the patient's expectations is key to a successful
      outcome. Deciding that these expectations are realistic requires a correct
      diagnosis and an inter-disciplinary treatment plan that is logical. This approach
      takes time and requires a comprehensive treatment discussion between the team
      members, and then a thorough case presentation to the patient. Only then will the
      patient begin to understand the extent of their problem and the options available
      to reconstruct their mouth.

PMID- 16902544
TI  - Variable presentation of temporalis hypertrophy--A case report with literature
      review.
AB  - A case of painful, initially bilateral, and then unilateral temporalis
      hypertrophy in a 33-year-old Caucasian woman is presented in a primary care
      setting; the aetiology of the hypertrophy was considered reactive in nature.
      Medical and supportive treatment was successful in providing symptomatic relief.
      Further treatment including an intramuscular botulinum injection was considered
      by the patient with a view to reduction of the chronic enlargement of her
      temporalis and masseter musculature. A review of the literature and previous
      treatment regimes is also presented.

PMID- 16902550
TI  - Dental nurses on perceived gender differences in their dentist's communication
      and interaction style.
AB  - OBJECTIVES: To investigate if dental nurses perceive gender differences in the
      communication and interaction style used by their dentist in general practice.
      METHODS: Data were collected from 64 Northern Irish dental nurses (70% response),
      and from 549 Dutch nurses (41% response). Respondents completed the Communication
      and Working Styles Questionnaire (CWSQ), a self-report questionnaire with 20
      items on staff communication and working styles. Using principal component
      analysis, six distinguishable factors could be extracted: [1] gender-related
      (four items, Cronbach's alpha = 0.78), [2] friendly relation (four items, alpha =
      0.66), [3] teamwork (four items, alpha = 0.44), [4] playfulness (two items, alpha
      = 0.69), [5] personal attention (three items, alpha = 0.60), and [6] business
      like (two items, alpha = 0.32). Factors [3] and [6] were additionally analysed at
      item level given their low internal consistencies. RESULTS: MANOVA indicated a
      main effect for dentist's gender [F(6,541) = 4.649, p < 0.001], and for country
      [F(6,541) = 37.601, p < 0.001] on the communication style scales. No interaction
      effect of gender with country was found. Nurses working with a male dentist had
      higher scores for the 'gender-related' communications styles, whereas those
      working with a female dentist had higher scores for 'friendly-relation' and
      'personal attention' communication styles. Dutch nurses had higher scores on
      'playfulness', whereas Northern Irish nurses had higher scores on 'friendly
      relation' and 'personal attention' communication styles. Some additional
      differences were found at item level. The age of the dental nurse explained some
      differences in communication and working styles [F(6,541) = 2.341, p = 0.031);
      younger dental nurses scored significantly higher for 'gender- related'
      communication and working style. CONCLUSION: Gender of the dentist does influence
      dental nurses' perceptions of the communication styles used in the primary dental
      care setting. Dental nurses working with female dentists report a style
      predominantly characterized by 'friendly-relation' and 'personal attention',
      whereas those working with a male dentist report 'gender-related' communication
      and working styles. Given the steadily growing percentage of females entering the
      dental profession, it is recommended to raise both dentists' and nurses'
      awareness on gender influences in professional communication by introducing these
      topics in their respective education.

PMID- 16902551
TI  - A qualitative study exploring barriers to a model of shared care for pre-school
      children's oral health.
AB  - OBJECTIVE: To explore the oral health beliefs and practices of primary health
      care professionals which may act as barriers to the development of a model of
      shared care for the oral health of pre-school children. DESIGN: Qualitative focus
      group discussions and semi-structured interviews. SETTING: Four rural local
      government areas in Victoria, Australia, 2003. SUBJECTS AND METHODS:  SUBJECTS:
      maternal and child health nurses, general medical practitioners, dental
      professionals and paediatricians working in the four local government areas. DATA
      COLLECTION: discipline specific focus groups and semi-structured interviews. DATA
      ANALYSIS: transcription, coding, clustering and thematic analysis. RESULTS:
      Several strong themes emerged from the data. All participants agreed that dental
      caries is a significant health issue for young children and their families.
      Beliefs about the aetiology of dental caries and its prevention were variable and
      often simplistic focusing predominantly on diet. Dental professionals did not
      believe that they had a primary role in the oral health of pre-school aged
      children but that others particularly maternal and child health nurses did.
      However other health care professionals were not confident in assuming this role.
      CONCLUSIONS: This study has identified important barriers and possible strategies
      for the development of an integrated and shared approach to preventing dental
      caries in pre-school aged children. Clear and consistent oral health information
      and agreed roles and responsibilities need to be developed.

PMID- 16902571
TI  - The 80-20 phenomenon (80:20 distribution of caries)--myth or fact.
AB  - For the past decade the phrase '80% of caries experience is found in 20% of the
      population' has been repeated so frequently, including by respected academics,
      that it has become accepted as fact by many in the dental profession. But is it a
      true representation of the state of dental health in the UK population, or an
      unsubstantiated convenient statement? Epidemiological data do not support the
      assertion.

PMID- 16902572
TI  - The standard for the duty to inform patients about risks: from the responsible
      dentist to the reasonable patient.
AB  - Complaints or claims against dentists by dissatisfied patients usually consist of
      three parts: the dentist did not perform the treatment as s/he should have done;
      the dentist did not inform the patient properly about the risks involved with the
      treatment; the dentist did not keep records. In most cases it is not too
      difficult for a judge or dental board member, if necessary with the aid of an
      expert witness, to decide whether the treatment was indeed below standard. The
      same applies to dentist's record keeping. The recrimination concerning the
      information given is something else. This deals with the extent of the duty to
      inform a patient as well as the proof that sufficient information was given.
      These difficulties do not only appear in court, but also in dental surgeries.
      This article will focus on the evolution in the jurisprudence concerning the duty
      to inform patients about risks as well as on the recently changed guidelines of
      the General Dental Council (GDC) regarding informed consent. Finally some simple
      tests will show that informing patients about risks does not have to be a risky
      and time consuming business for the dentist.

PMID- 16902573
TI  - A randomised controlled trial of clinical outreach education to rationalise
      antibiotic prescribing for acute dental pain in the primary care setting.
AB  - OBJECTIVE: To assess the effect of educational outreach visits on antibiotic
      prescribing for acute dental pain in primary care. STUDY DESIGN: RCT. SETTING:
      General dental practices in four health authority areas in Wales. SUBJECTS AND
      METHODS: General dental practitioners were recruited to the study and randomly
      allocated to one of the three study groups (control group, guideline group or
      intervention group). Following the intervention, practitioners completed a
      standardised questionnaire for each patient that presented with acute dental
      pain. INTERVENTIONS: The control group received no intervention. The guideline
      group received educational material by post. The intervention group received
      educational material by post and an academic detailing visit by a trained
      pharmacist. The educational material included evidence-based guidelines on
      prescribing for acute dental pain and patient information leaflets. MAIN OUTCOME
      MEASURES: The number of antibiotic prescriptions issued to patients presenting
      with dental pain and the number of 'inappropriate' antibiotic prescriptions.
      Antibiotics were considered to be inappropriate if the patient did not have
      symptoms indicative of spreading infection. RESULTS: A total of 1,497 completed
      questionnaires were received from 23, 20 and 27 general dental practitioners in
      the control, guideline and intervention group respectively. Patients in the
      intervention group received significantly fewer antibiotic prescriptions than
      patients in the control group (OR (95% CI) 0.63 (0.41, 0.95)) and significantly
      fewer inappropriate antibiotic prescriptions (OR (95% CI) 0.33 (0.21, 0.54)).
      However, antibiotic and inappropriate antibiotic prescribing were not
      significantly different in the guideline group compared to the control group (OR
      (95% CI) 0.83 (0.55, 1.21) and OR (95% CI) 0.82 (0.53, 1.29) respectively).
      CONCLUSIONS: Strategies based upon educational outreach visits may be
      successfully employed to rationalise antibiotic prescribing by dental
      practitioners.

PMID- 16902574
TI  - Undergraduate orthodontic assessment and examination in UK dental schools.
AB  - AIMS AND OBJECTIVES: This paper assesses the current internal assessment and BDS
      examination of undergraduate orthodontics in UK dental schools, the changes which
      have occurred in the last three years, and future changes proposed. METHOD:
      Questionnaires were emailed to the undergraduate orthodontic course leaders in
      each of the UK dental schools. Twelve dental schools agreed to participate in the
      survey. Responses were checked for completeness, summarised and sent back to
      individual course leaders to verify. These verified responses were then analysed.
      RESULTS: There was a wide variation in the form and content of the in-course
      assessment and the BDS examination in the 12 UK dental schools. The in-course
      assessment varied from minimal to extensive, and in its percentage contribution
      to BDS. The use of written, clinical, and particularly patient treatment and
      laboratory assessments varied considerably from school to school. The format of
      the BDS examination varied in the number, type and timing of written
      examinations, in the number of students examined clinically, and in the use of
      additional examinations of viva, case presentation, or OSCE. CONCLUSIONS:
      Comparison of undergraduate orthodontic courses in UK dental schools revealed a
      wide variation in student assessment and examination. Current orthodontic
      internal assessments are inconsistent with no common pattern across the courses,
      and inconsistencies also exist in the BDS examination. Guidelines for orthodontic
      assessment and examination are needed to ensure standards and consistency in UK
      dental schools in the future.

PMID- 16902575
TI  - The nuclear pore complex, nuclear transport, and apoptosis.
AB  - The nuclear pore complex (NPC) is the sole gateway between the nucleus and the
      cytoplasm of interphase eukaryotic cells, and it mediates all trafficking between
      these 2 cellular compartments. As such, the NPC and nuclear transport play
      central roles in translocating death signals from the cell membrane to the
      nucleus where they initiate biochemical and morphological changes occurring
      during apoptosis. Recent findings suggest that the correlation between the NPC,
      nuclear transport, and apoptosis goes beyond the simple fact that NPCs mediate
      nuclear transport of key players involved in the cell death program. In this
      context, the accessibility of key regulators of apoptosis appears to be highly
      modulated by nuclear transport (e.g., impaired nuclear import might be an
      apoptotic trigger). In this review, recent findings concerning the unexpected
      tight link between NPCs, nuclear transport, and apoptosis will be presented and
      critically discussed.

PMID- 16902576
TI  - G-protein-coupled receptors signalling at the cell nucleus: an emerging paradigm.
AB  - G-protein-coupled receptors (GPCRs) comprise a wide family of monomeric
      heptahelical glycoproteins that recognize a broad array of extracellular
      mediators including cationic amines, lipids, peptides, proteins, and sensory
      agents. Thus far, much attention has been given towards the comprehension of
      intracellular signaling mechanisms activated by cell membrane GPCRs, which
      convert extracellular hormonal stimuli into acute, non-genomic (e.g., hormone
      secretion, muscle contraction, and cell metabolism) and delayed, genomic
      biological responses (e.g., cell division, proliferation, and apoptosis).
      However, with respect to the latter response, there is compelling evidence for a
      novel intracrine mode of genomic regulation by GPCRs that implies either the
      endocytosis and nuclear translocation of peripheral-liganded GPCR and (or) the
      activation of nuclearly located GPCR by endogenously produced, nonsecreted
      ligands. A noteworthy example of the last scenario is given by heptahelical
      receptors that are activated by bioactive lipoids (e.g., PGE(2) and PAF), many of
      which may be formed from bilayer membranes including those of the nucleus. The
      experimental evidence for the nuclear localization and signalling of GPCRs will
      be reviewed. We will also discuss possible molecular mechanisms responsible for
      the atypical compartmentalization of GPCRs at the cell nucleus, along with their
      role in gene expression.

PMID- 16902577
TI  - NPY, ET-1, and Ang II nuclear receptors in human endocardial endothelial cells.
AB  - Neuropeptide Y (NPY), endothelin-1 (ET-1), and angiotensin II (Ang II) are
      peptides that are known to play many important roles in cardiovascular
      homeostasis. The physiological actions of these peptides are thought to be
      primarily mediated by plasma membrane receptors that belong to the G-protein
      coupled receptor superfamily. However, there is increasing evidence that suggests
      the existence of functional G-protein-coupled receptors at the level of the
      nucleus and that the nucleus could be a cell within a cell. Here, we review our
      work showing the presence in the nucleus of the NPY Y(1) receptor, the ET(A) and
      ET(B) receptors, as well as the AT(1) and AT(2) receptors and their respective
      ligands. This work was carried out in 20-week-old fetal human endocardial
      endothelial cells. Our results demonstrate that nuclear Y1, AT(1), and ET(A)
      receptors modulate nuclear calcium in these cells.

PMID- 16902578
TI  - The role of nuclear envelope calcium in modifying nuclear pore complex structure.
AB  - Some of the most important trafficking processes in cells involve transport
      across the nuclear envelope. Whether it is the import of transcription factors or
      the export of RNA, the only known portal across the double lipid bilayer that
      forms the nuclear envelope are the macromolecular pores known as nuclear pore
      complexes (NPCs). Understanding how signals influence the conformation of the NPC
      is important for testing models of, and perhaps modifying, transport across the
      nuclear envelope. Here we summarize high-resolution atomic force microscopy
      studies of NPC structure following manipulation of nuclear envelope calcium
      stores of nuclei from Xenopus laevis oocytes. The results show that the release
      of calcium from these stores through the specific activation of inositol 1,4,5
      trisphosphate receptors leads to changes in NPC structure observable from both
      sides of the nuclear envelope. The diameter of the NPC is also sensitive to these
      calcium stores and increases upon calcium release. Western blot analysis reveals
      the presence of ryanodine receptors in the nuclear envelope of X. laevis oocytes,
      although in low abundance. Activation of these calcium channels also leads to the
      displacement of the central mass and changes in NPC diameter. This change in
      structure may involve a displacement of the cytoplasmic and nuclear rings of the
      NPC towards each other, leading to the apparent emergence of the central mass
      from both sides of the NPC. The changes in conformation and diameter of the NPC
      may alter cargo access and binding to phenylalanine-glycine repeats lining the
      pore, thus altering transport.

PMID- 16902579
TI  - Somatic DNA recombination in the brain.
AB  - Possible somatic DNA recombination in the brain has been investigated by
      attempting to capture direct or indirect evidence of it. Until recently, the
      biological significance of the DNA event, the genes is involved in the
      recombination, or even whether the event actually occurs in the brain has
      remained unclear. The DNA-rearranged locus-oriented approach and the
      recombination activity-oriented approach have mutually contributed to the
      elucidation of the biological features of extra-immune system somatic DNA
      recombination. There have been only 2 loci proposed for the candidate, one is a
      repetitive sequence and the other DNA recombination is nonrepetitive locus. This
      review states conventional concepts and discussions chronologically and finally
      to the newest aspects of DNA rearrangement in the brain.

PMID- 16902580
TI  - Calcium signaling in the nucleus.
AB  - Cytosolic Ca(2+) is a versatile secondary messenger that regulates a wide range
      of cellular activities. In the past decade, evidence has accumulated that free
      Ca(2+) within the nucleus also plays an important messenger function. Here we
      review the mechanisms and effects of Ca(2+) signals within the nucleus. In
      particular, evidence is reviewed that the nucleus contains the machinery
      necessary for production of inositol 1,4,5-trisphosphate and for inositol 1,4,5
      trisphosphate receptor-mediated Ca(2+) release. The role of Ca(2+) signals within
      the nucleus is discussed including regulation of such critical cell functions as
      gene expression, activation of kinases, and permeability of nuclear pores.

PMID- 16902581
TI  - Will you let me use your nucleus? How Agrobacterium gets its T-DNA expressed in
      the host plant cell.
AB  - Agrobacterium is the only known bacterium capable of natural DNA transfer into a
      eukaryotic host. The genes transferred to host plants are contained on a T-DNA
      (transferred DNA) molecule, the transfer of which begins with its translocation,
      along with several effector proteins, from the bacterial cell to the host-cell
      cytoplasm. In the host cytoplasm, the T-complex is formed from a single-stranded
      copy of the T-DNA (T-strand) associated with several bacterial and host proteins
      and it is imported into the host nucleus via interactions with the host nuclear
      import machinery. Once inside the nucleus, the T-complex is most likely directed
      to the host genome by associating with histones. Finally, the chromatin
      associated T-complex is uncoated from its escorting proteins prior to the
      conversion of the T-strand to a double-stranded form and its integration into the
      host genome.

PMID- 16902582
TI  - Current concepts in nuclear pore electrophysiology.
AB  - Over 4 decades ago, microelectrode studies of in situ nuclei showed that, under
      certain conditions, the nuclear envelope (NE) behaves as a barrier opposing the
      nucleocytoplasmic flow of physiological ions. As the nuclear pore complexes
      (NPCs) of the NE are the only pathways for direct nucleocytoplasmic flow, those
      experiments implied that the NPCs are capable of restricting ion flow. These
      early studies validated electrophysiology as a useful approach to quantify some
      of the mechanisms by which NPCs mediate gene activity and expression. Since
      electron microscopy (EM) and other non-electrophysiological investigations,
      showed that the NPC lumen is a nanochannel, the opinion prevailed that the NPC
      could not oppose the flow of ions and, therefore, that electrophysiological
      observations resulted from technical artifacts. Consequently, the initial
      enthusiasm with nuclear electrophysiology faded out in less than a decade. In
      1990, nuclear electrophysiology was revisited with patch-clamp, the most powerful
      electrophysiological technique to date. Patch-clamp has consistently demonstrated
      that the NE has intrinsic ion channel activity. Direct demonstrations of the NPC
      on-off ion channel gating behavior were published for artificial conditions in
      1995 and for intact living nuclei in 2002. This on-off switching/gating behavior
      can be interpreted in terms of a metastable energy barrier. In the hope of
      advancing nuclear electrophysiology, and to complement the other papers contained
      in this special issue of the journal, here I review some of the main technical,
      experimental, and theoretical issues of the field, with special focus on NPCs.

PMID- 16902583
TI  - Nuclear import of spliceosomal snRNPs.
AB  - Uridine-rich small nuclear ribonucleoproteins (U snRNPs) are the building units
      of the spliceosome. These RNA and protein complexes assemble in the cytoplasm.
      After proper assembly and RNA maturation, mature U snRNPs are imported into the
      cell nucleus, where they take part in the splicing process. In this paper we
      review the current knowledge of how U snRNPs enter the nucleus.

PMID- 16902585
TI  - GM1 ganglioside: another nuclear lipid that modulates nuclear calcium. GM1
      potentiates the nuclear sodium-calcium exchanger.
AB  - The nuclear envelope (NE) enclosing the cell nucleus, although morphologically
      and chemically distinct from the plasma membrane, has certain features in common
      with the latter including the presence of GM1 as an important modulatory
      molecule. This ganglioside influences Ca(2+) flux across both membranes, but by
      quite different mechanisms. GM1 in the NE contributes to regulation of nuclear
      Ca(2+) through potentiation of a Na(+)/Ca(2+) exchanger in the inner nuclear
      membrane, whereas in the cell membrane, it regulates cytosolic Ca(2+) through
      modulation of a nonvoltage-gated Ca(2+) channel. Studies with neuroblastoma cells
      suggest GM1 concentration becomes elevated in the NE with onset of axonogenesis.
      However, the nuclear GM1/exchanger complex is not limited to neuronal cells but
      also occurs in NE of astrocytes, C6 cells, and certain non-neural cells.
      Immunoprecipitation and immunoblot experiments have shown high affinity
      association of the nuclear Na(+)/Ca(2+) exchanger with GM1, in contrast to
      Na(+)/Ca(2+) exchangers of the plasma membrane, which bind GM1 less avidly or not
      at all. This is believed to be due to different isoforms of the exchanger and a
      difference in topology of GM1 relative to the large inner loop of the exchanger
      in the 2 membranes. Cultured neurons from mice genetically engineered to lack GM1
      suffered Ca(2+) dysregulation as seen in their high vulnerability to Ca(2+)
      induced apoptosis. They were rescued by GM1 and more effectively by LIGA20, a
      membrane-permeant derivative of GM1. The mutant animals were highly susceptible
      to kainate-induced seizures, which are also a reflection of Ca(2+) dysregulation.
      The seizures were effectively attenuated by LIGA20 in parallel with the ability
      of this agent to enter brain cells, insert into the NE, and potentiate
      Na(+)/Ca(2+) exchange activity in the nucleus. The Na(+)/Ca(2+) exchanger of the
      NE, in association with nuclear GM1, is thus seen contributing to independent
      regulation of Ca(2+) by the nucleus in a manner that provides cytoprotection
      against Ca(2+)-induced apoptosis.

PMID- 16902584
TI  - Intracrine signaling through lipid mediators and their cognate nuclear G-protein
      coupled receptors: a paradigm based on PGE2, PAF, and LPA1 receptors.
AB  - Prostaglandins (PGs), platelet-activating factor (PAF), and lysophosphatidic acid
      (LPA) are ubiquitous lipid mediators that play important roles in inflammation,
      cardiovascular homeostasis, and immunity and are also known to modulate gene
      expression of specific pro-inflammatory genes. The mechanism of action of these
      lipids is thought to be primarily dependent on their specific plasma membrane
      receptors belonging to the superfamily of G-protein-coupled receptors (GPCR).
      Increasing evidence suggests the existence of a functional intracellular GPCR
      population. It has been proposed that immediate effects are mediated via cell
      surface receptors whereas long-term responses are dependent upon intracellular
      receptor effects. Indeed, receptors for PAF, LPA, and PGE(2) (specifically EP(1),
      EP(3), and EP(4)) localize at the cell nucleus of cerebral microvascular
      endothelial cells of newborn pigs, rat hepatocytes, and cells overexpressing each
      receptor. Stimulation of isolated nuclei with these lipids reveals biological
      functions including transcriptional regulation of major genes, namely c-fos,
      cylooxygenase-2, and endothelial as well as inducible nitric oxide synthase. In
      the present review, we shall focus on the nuclear localization and signaling of
      GPCRs recognizing PGE(2), PAF, and LPA phospholipids as ligands. Mechanisms on
      how nuclear PGE2, PAF, and LPA receptors activate gene transcription and nuclear
      localization pathways are presented. Intracrine signaling for lipid mediators
      uncover novel pathways to elicit their effects; accordingly, intracellular GPCRs
      constitute a distinctive mode of action for gene regulation.

PMID- 16902586
TI  - Mechanism regulating nuclear calcium signaling.
AB  - Although the outer nuclear membrane is continuous with the endoplasmic reticulum,
      it is possible to isolate nuclei both intact and free from endoplasmic reticulum
      contaminants. The outer and the inner nuclear membranes can be purified free from
      cross-contamination. Evidence in support of autonomous regulation of nuclear
      calcium signaling relies upon the investigations with isolated nuclei. Mechanisms
      for generating calcium signaling in the nucleus have been identified. Two calcium
      transporting systems, an ATP-dependant nuclear Ca(2+)-ATPase and an IP4-mediated
      inositol 1,3,4,5-tetrakisphosphate receptor, are located on the outer nuclear
      membrane. Thus, ATP and IP4, depending on external free calcium concentrations,
      are responsible for filling the nuclear envelope calcium pool. The inositol 1,4,5
      trisphosphate receptor is located on the inner nuclear membrane with its ligand
      binding domain facing toward the nucleoplasm. Likewise, the ryanodine receptor is
      located on the inner nuclear membrane and its ligand cADP-ribose is generated
      within the nucleus. A 120 kDa protein fragment of nuclear PLC-gamma1 is
      stimulated in vivo by epidermal growth factor nuclear signaling coincident with
      the time course of nuclear membrane epidermal growth factor receptor activation.
      Stimulated 120 kDa protein fragment interacts with PIKE, a nuclear GTPase, and
      together they form a complex with PI[3]kinase serving as a module for nuclear
      PI[3]K stimulation. Thus, the nucleus has its own IP(3) generating system.

PMID- 16902587
TI  - High resolution analysis of mammalian nuclear structure throughout the cell
      cycle: implications for nuclear pore complex assembly during interphase and
      mitosis.
AB  - Nuclear pore complexes (NPCs) are the gateways for both active and passive
      bidirectional molecular transport between the nucleoplasm and cytoplasm. These
      mega-dalton assemblies are composed of multiple copies of approximately 30
      distinct proteins termed nucleoporins. Higher eukaryotes display an "open"
      mitosis in which the NPCs, nuclear envelope, and lamina disassemble. During
      mitosis several nucleoporins are redistributed to kinetochores until they are
      recruited back to the periphery of chromatin as the NPCs are reassembled. Within
      this study we have developed and optimized the visualization of mammalian cells
      and their chromosome profiles throughout the cell-cycle. Close attention has been
      paid to the preservation of chromatin, membranes, and NPC structure to
      investigate the ultrastructural locations of specific proteins in both interphase
      and mitosis.

PMID- 16902588
TI  - G-protein-coupled receptors, channels, and Na+-H+ exchanger in nuclear membranes
      of heart, hepatic, vascular endothelial, and smooth muscle cells.
AB  - The action of several peptides and drugs is thought to be primarily dependent on
      their interactions with specific cell surface G-protein-coupled receptors and
      ionic transporters such as channels and exchangers. Recent development of 3-D
      confocal microscopy allowed several laboratories, including ours, to identify and
      study the localization of receptors, channels, and exchangers at the
      transcellular level of several cell types. Using this technique, we demonstrated
      in the nuclei of several types of cells the presence of Ca(2+) channels as well
      as Na(+)-H(+) exchanger and receptors such as endothelin-1 and angiotensin II
      receptors. Stimulation of these nuclear membrane G-protein-coupled receptors
      induced an increase of nuclear Ca(2+). Our results suggest that, similar to the
      plasma membrane, nuclear membranes possess channels, exchangers and receptors
      such as those for endothelin-1 and angiotensin II, and that the nucleus seems to
      be a cell within a cell. This article will emphasize these findings.

PMID- 16902589
TI  - Somatic DNA recombination in a mouse genomic region, BC-1, in brain and non-brain
      tissue.
AB  - The genomic region BC-1 (GenBank acc. No. AB075899) on mouse chromosome 16 has
      been reported as a genomic region undergoing somatic DNA recombination producing
      circular DNA and genomic deletion in brain during late embryogenesis. The present
      study shows that the BC-1 circular DNA production had already started on the 13th
      day of embryonic age, earlier than the previous observation that the circular DNA
      production started on the 15th through 17th embryonic day. The BC-1 deletion was
      also observed in the spleen and ocular lens. In situ hybridization analysis
      indicated that a human-homologous region in the BC-1 sequence was expressed in
      the lens at a perinatal period. These data suggest that the somatic DNA
      recombination in the BC-1 region is not restricted to brain tissue, and that the
      BC-1 DNA recombination relates to lens development.

PMID- 16902590
TI  - Decondensation of Xenopus sperm chromatin using Saccharomyces cerevisiae whole
      cell extracts.
AB  - Biochemical studies using highly condensed Xenopus sperm chromatin and protein
      extracts prepared from multiple systems have lead to the identification of
      conserved proteins involved in chromosome decondensation. However, mutations to
      these proteins are unavailable as the systems used are not amenable to genetic
      studies. We took a genetic approach to isolating chromosome decondensation
      mutants by incubating Xenopus sperm chromatin with whole-cell extracts prepared
      from the Hartwell library of random temperature sensitive (ts) yeast cells. We
      show that decondensation of Xenopus sperm chromatin using wild type yeast
      extracts was rapid, ATP- and extract-dependent, and resistant to heat, N
      ethylmaleimide, protease K, RNase A, and micrococcal nuclease. From 100 mutant
      extracts screened, we obtained one strain, referred to as rmc4, that was
      chromosome decondensation defective. The mutant was slow growing and exhibited
      germination defects. Low concentrations of rmc4 extract would eventually
      decondense sperm heads, and fractionation of the mutant extract produced a
      decondensation competent fraction, suggesting the presence of an overactive
      inhibitor in rmc4 cells. We performed a multicopy suppressor screen that
      identified PDE2, a gene encoding a protein that inhibits protein kinase A (PKA)
      activity. As PKA was previously shown in human cells to maintain condensed
      chromatin, our results suggest that PKA activity is elevated in rmc4 cells,
      causing a decondensation defect. Thus, our experiments reveal that yeast encodes
      an evolutionarily conserved chromosome decondensation activity that can be
      genetically manipulated.

PMID- 16902591
TI  - Endonuclear lipids in liver cells.
AB  - Lipids are not only components of cell nucleus membranes, but are also found in
      the membrane-depleted nuclei where they fulfill special functions. We have
      investigated the lipid composition of membrane-depleted rat liver nuclei obtained
      by incubation with low Triton X-100 concentrations of 0.04% and 0.08%, which
      rendered them unaltered or hardly altered. Under these conditions, 26% of
      proteins and 22% of phospholipids were recovered. The main phospholipids were
      phosphatidylcholine > phosphatidylethanolamine > phosphatidylinositol = or >
      phosphatidylserine and sphingomyelin (in decreasing concentrations). The fatty
      acid components of total lipids and phosphatidylcholine were mainly unsaturated.
      Over 40% belonged to the n-6 series (arachidonic > or = 25% and linoleic 15%);
      approximately 40% corresponded to saturated acids and <10% were monoenoic.
      Endonuclear phosphatidylcholine was built up by 16 molecular species, the most
      abundant being 18:0-20:4 (32%), 16:0-20:4 (19%), 16:0-18:2 (13%), and 18:0-18:2
      (11%). The fatty acid composition and phosphatidylcholine molecular species
      distribution in the membrane-depleted nucleus of rat liver showed patterns
      similar to the whole nucleus, mitochondria, microsomes, and homogenate of the
      parent liver cells, suggesting that endonuclear lipid pool composition is mainly
      determined by a liver organ profile.

PMID- 16902592
TI  - Effects of mitogen-activated protein kinases on nuclear protein import.
AB  - ERK-2 MAP kinase activation induces inhibitory effects on nuclear protein import
      in vascular smooth muscle cells. The mechanism and characteristics of this effect
      of ERK-2 were investigated. An unusual dose-dependent effect of ERK-2 on nuclear
      protein import was identified. At higher concentrations (1 microg/mL) of ERK-2,
      nuclear protein import was stimulated, whereas lower concentrations (0.04
      microg/mL) inhibited import. Intermediate concentrations exerted intermediate
      effects. The stimulatory and inhibitory effects at the 2 different ERK-2
      concentrations were observed in both conventional, permeabilized cell assays of
      nuclear protein import and with in situ microinjection of smooth muscle cells.
      The biphasic effects of ERK-2 on import were also found for the other 2 members
      of the MAPK family, p38 and JNK. RanGAP was identified by structural analysis as
      a candidate target protein responsible for mediating the effects of ERK-2. After
      pretreatment with high concentrations of ERK-2, RanGAP activity was significantly
      increased by approximately 50%. In contrast, low concentrations of ERK-2
      significantly attenuated RanGAP activity. These results demonstrate that all 3
      members of the MAPK family can alter nuclear protein import in opposite
      directions depending upon the concentration of ERK-2 used. RanGAP represents the
      MAP kinase target whereby nuclear transport can be stimulated or inhibited.

PMID- 16902593
TI  - The nuclear tubular invaginations are dynamic structures inside the nucleus of
      HeLa cells.
AB  - Nuclear tubules (NTs) were found in the nucleus of HeLa cells. Although no
      function has been ascribed to these structures, our previous data has shown that
      they are the sites of Ca(2+) release with mitochondria shuttled around. In the
      present study, we further characterized these NTs through different fluorescent
      dye-labeling and red fluorescent protein transfection experiments. We found that
      doxorubicin (Dox) is a good indicator to demonstrate the NTs since Dox is
      fluorescent and DNA is able to quench its fluorescence. By using confocal and
      electron microscopy, we show that the number and nature of the NTs in HeLa vary
      from cell to cell, ranging from tubular to intricately branched structures.
      Additionally, these NTs are double-membrane invaginations of the nuclear envelope
      and usually lie close to nucleolus. At rest, NTs appeared to be stable and their
      mouths are always closed. Upon Ca(2+) ionomycin stimulation, various forms of
      dynamism, including membrane protrusion to the nucleus, enlargement and shrinkage
      of the NTs, and distortion of the nuclear envelope and NTs were observed over a
      time scale of minutes. These observations suggest that the NT represents a
      specialized and dynamic compartment inside the nucleus under the control of
      Ca(2+).

PMID- 16902595
TI  - Getting across the nuclear pore complex: new insights into nucleocytoplasmic
      transport.
AB  - Small ions and molecules can traverse the nuclear pore complex (NPC) simply by
      diffusion, whereas larger proteins and RNAs require specific signals and factors
      that facilitate their passage through the NPC. Our understanding of the factors
      that participate and regulate nucleocytoplasmic transport has increased
      tremendously over the past years, whereas the actual translocation step through
      the NPC has remained largely unclear. Here, we present and discuss recent
      findings on the interaction between the NPC and transport receptors and provide
      new evidence that the NPC acts as a constrained diffusion pore for molecules and
      particles without retention signal and as an affinity gate for signal-bearing
      cargos.

PMID- 16902594
TI  - Stretch induced accumulation of total Ca and Na in cytosol and nucleus: a
      comparison between cardiac trabeculae and isolated myocytes.
AB  - By means of electron probe microanalysis (EPMA), we quantified changes in total
      sodium [Na] and calcium [Ca] concentration owing to the following: (i) local
      axial stretch (LAS) of isolated rat myocytes and (ii) end-to-end stretch (ETES)
      of rat ventricular trabeculae. For LAS, the distance between patch pipette and a
      cell-attached stylus was increased by maximally 20%; this activated a
      nonselective cationic current I(SAC) of approximately -0.5 nA, which was blocked
      by streptomycin. Trabeculae were stretched end-to-end from 85% L(max) to L(max).
      Stretch increased cytosolic [Na](total) by 34% in isolated myocytes (p < 0.001)
      and by 43% in trabeculae (p < 0.001). The increment in nuclear [Na](total) was
      21% in myocytes (p < 0.01) and 20% in trabeculae (p < 0.001). Stretch increased
      [Ca](total) in isolated myocytes, in both cytosol (from 0.63 +/- 0.09 to 1.09 +/-
      0.20 mmol/L, p < 0.05) and nucleus (from 0.33 +/- 0.05 to 0.64 +/- 0.13 mmol/L, p
      < 0.05). In trabeculae, the stretch-induced increment of 51% in cytosolic
      [Ca](total) remained nonsignificant (p < 0.15). In the nucleus, [Ca](total) did
      not change. We interpret the difference of stretch on nuclear calcium in myocytes
      vs. trabeculae with the assumption that LAS, but not ETES, produces shear-stress
      components that translate the mechanical stimulus deeply into the cell where it
      may modulate [Ca](total) by signals independent of I(SAC).

PMID- 16902596
TI  - Regulation of the sarcoplasmic reticulum Ca2+-ATPase expression in the
      hypertrophic and failing heart.
AB  - The sarcoplasmic reticulum (SR) plays a central role in the contraction and
      relaxation coupling in the myocardium. The SR Ca(2+)-ATPase (SERCA2) transports
      Ca(2+) inside the SR lumen during relaxation of the cardiac myocyte. It is well
      known that diminished contractility of the hypertrophic cardiac myocyte is the
      main factor of ventricular dysfunction in the failing heart. A key feature of the
      failing heart is a decreased content and activity of SERCA2, which is the cause
      of some of the physiological defects observed in the hypertrophic cardiomyocyte
      performance that are important during transition of compensated hypertrophy to
      heart failure. In this review different possible mechanisms responsible for
      decreased transcriptional regulation of the SERCA2 gene are examined, which
      appear to be the primary cause for decreased SERCA2 expression in heart failure.
      The experimental evidence suggests that several signalling pathways are involved
      in the downregulation of SERCA2 expression in the hypertrophic and failing
      cardiomyocyte. Therapeutic upregulation of SERCA2 expression using replication
      deficient adenoviral expression vectors, pharmacological interventions using
      thyroid hormone analogues, beta-adrenergic receptor antagonists, and novel
      metabolically active compounds are currently under investigation for the
      treatment of uncompensated cardiac hypertrophy and heart failure.

PMID- 16902597
TI  - Short-term passive smoking causes endothelial dysfunction via oxidative stress in
      nonsmokers.
AB  - Recent studies have shown that passive smoking impairs vascular endothelial
      function and induces oxidative stress in humans. However, in most of the previous
      human data regarding tobacco-induced pathophysiology, vascular endothelial
      dysfunction and oxidative stress have been separately assessed. This study was
      designed to determine the association between the acute effect of passive smoking
      on vascular endothelial function and in-vivo oxidative stress status. We studied
      30 healthy male Japanese volunteers (32 +/- 7 years) including 15 habitual
      smokers and 15 nonsmokers. After baseline echocardiographic, hemodynamic
      recording, and blood sampling, subjects were exposed to passive smoking for 30
      min. Endothelium-dependent vasodilation was measured by using % flow-mediated
      vasodilation (%FMD) of the brachial artery and plasma levels of 8-isoprostane was
      measured by enzyme immunoassay before and after the passive smoking exposure.
      Baseline %FMD was lower (4.3% +/- 1.2% vs. 10.9% +/- 3.1%, p < 0.001) and
      baseline plasma 8-isoprostane level was higher (41.5 +/- 5.8 pg/mL vs. 26.9 +/-
      5.4 pg/mL, p < 0.001) in smokers than those in nonsmokers. The %FMD and 8
      isoprostane level did not change after passive smoking in smokers. In nonsmokers,
      however, the %FMD decreased (to 5.0% +/- 1.9%, p < 0.001) and the 8-isoprostane
      level increased (to 37.8 +/- 9.6 pg/mL, p < 0.001) significantly after 30 min
      passive smoking exposure, equivalently to the levels of smokers. Sixty corrected
      samples before and after passive smoking exposure in all patients showed a
      significant negative correlation between the % FMD and the plasma 8-isoprostane
      levels (n = 60, r = -0.69, p < 0.001). Even 30 min of passive smoking rapidly
      impairs vascular endothelial function, which is associated with oxidative stress.
      Our data provide the pathophysiological insight for the recent epidemiological
      evidence about the increased risk of coronary heart disease among nonsmokers
      exposed to passive smoking.

PMID- 16902598
TI  - Montelukast prevents the decrease of interleukin-10 and inhibits NF-kappaB
      activation in inflammatory airway of asthmatic guinea pigs.
AB  - Interleukin (IL)-10 is an important immunoregulatory and anti-inflammatory
      cytokine, whereas nuclear factor-kappaB (NF-kappaB) plays an important role in
      the pathogenesis of asthma. In the present study, the effects of montelukast on
      the level of IL-10 and on the activation of NF-kappaB in the inflammatory airway
      of asthmatic guinea pigs were investigated. Guinea pigs were sensitized by
      ovalbumin. Pulmonary inflammation was observed by hematoxylin and eosin staining.
      The eosinophils in broncho-alveolar lavage fluid and blood were separated by
      density gradient centrifugation and counted under microscope. The level of IL-10
      in broncho-alveolar lavage fluid was measured by enzyme-linked immunoadsorbent
      assay. Activation of NF-kappaB in lung tissues was inspected by
      immunohistochemistry. Montelukast at medium and high doses prevented the decrease
      of IL-10 in broncho-alveolar lavage fluid (n = 8, p < 0.01 vs. asthma model
      group), inhibited the activation of NF-kappaB in lung tissues (n = 8; medium
      dose, p < 0.05; high dose, p < 0.01; vs. asthma model group). There was a
      significantly negative correlation between the level of IL-10 and the activation
      of NF-kappaB in lung tissues (r = -0.488, p < 0.01). Montelukast reduced the
      severity of airway inflammation and the number of eosinophils in asthmatic guinea
      pigs. From all these findings we conclude that montelukast can prevent the
      decrease of IL-10 and inhibit the activation of NF-kappaB in inflammatory airway
      of asthmatic guinea pigs, which may be the new important mechanisms of
      montelukast's anti-airway-inflammation effects in asthmatic guinea pigs.

PMID- 16902599
TI  - Role of cyclic GMP and calcineurin in homologous and heterologous desensitization
      of natriuretic peptide receptor-A.
AB  - The natriuretic peptide receptor-A (NPR-A) mediates natriuretic, hypotensive, and
      antihypertrophic effects of natriuretic peptides through the production of cGMP.
      In pathological conditions such as heart failure, these effects are attenuated by
      homologous and heterologous desensitization mechanisms resulting in the
      dephosphorylation of the cytosolic portion of the receptor. In contrast with
      natriuretic peptide-induced desensitization, pressor hormone-induced
      desensitization is dependent on protein kinase C (PKC) stimulation and (or)
      cytosolic calcium elevation. Mechanisms by which PKC and Ca(2+) promote NPR-A
      desensitization are not known. The role of cGMP and of the cytosolic Ca(2+)
      pathways in NPR-A desensitization were therefore studied. In contrast with the
      activation of NPR-A by its agonist, activation of soluble guanylyl cyclases of
      LLC-PK1 cells by sodium nitroprusside also leads to a production of cGMP but
      without altering NPR-A activation. Consequently, cGMP elevation per se does not
      appear to mediate homologous desensitization of NPR-A. In addition, cytosolic
      calcium increase is required only for the heterologous desensitization pathway
      since the calcium chelator BAPTA-AM blocks only PMA or ionomycin-induced
      desensitization. Calcineurin inhibitors block the NPR-A guanylyl cyclase
      heterologous desensitization induced by ionomycin, suggesting an essential role
      for this Ca(2+)-stimulated phosphatase in NPR-A desensitization. In summary, the
      present report demonstrates that neither cGMP nor Ca(2+) cytosolic elevation
      cause NPR-A homologous desensitization. Our results also indicate for the first
      time a role for calcineurin in NPR-A heterologous desensitization.

PMID- 16902600
TI  - Implication of mitochondrial dysfunction and cell death in cold preservation-
      warm reperfusion-induced hepatocyte injury.
AB  - Cold ischemia--warm reperfusion (CI/WR) injury of liver transplantation involves
      hepatocyte cell death, the nature and underlying mechanisms of which remain
      unclear. Isolated hepatocytes and isolated perfused livers were used to determine
      the prevalence of necrosis and apoptosis as well as mitochondrial dysfunction. In
      isolated cells, propidium iodide and Hoechst 33342 staining showed a cold
      storage, time-dependent increase in necrosis, whereas apoptosis was minimal even
      after 48 h of hypothermia. Nonetheless, a progressive loss of mitochondrial
      membrane potential was observed. Translocation of mitochondrial cytochrome c
      toward microsomes occurred within 24 h of CI/WR, with cytochrome c reaching the
      cytosol later. Mitochondria isolated from whole livers subjected to CI/WR also
      display reduced metabolic parameters and increased susceptibility to swelling.
      These events are associated with increased activity of major initiator (caspase
      9) and effector (caspase 3) caspases. The results demonstrate that CI/WR induces
      mitochondrial dysfunction in isolated cells and in the whole organ; only in the
      latter is that sufficient to trigger the classical mitochondrial pathway of
      apoptosis. Our study also provides evidence for the involvement of endoplasmic
      reticulum stress in CI/WR hepatocyte injury. Combined protection of mitochondria
      and endoplasmic reticulum may thus represent an innovative therapeutic avenue to
      enhance liver graft viability and functional integrity.

PMID- 16902601
TI  - Prolactin directly enhanced Na+/K+- and Ca2+-ATPase activities in the duodenum of
      female rats.
AB  - Prolactin has recently been shown to directly stimulate 2 components of the
      active duodenal calcium transport in female rats, i.e., solvent drag-induced and
      transcellular-active calcium transport. Since the basolateral Na(+)/K(+)- and
      Ca(2+)-ATPases, respectively, play important roles in these 2 transport
      mechanisms, the present study aimed to examine the direct actions of prolactin on
      the activities of both transporters in sexually mature female Wistar rats. The
      results showed that 200, 400, and 800 ng/mL prolactin produced a significant
      increase in the total ATPase activity of duodenal crude homogenate in a dose
      dependent manner within 60 min (i.e., from a control value of 1.53 +/- 0.13 to
      2.29 +/- 0.21 (p < 0.05), 2.68 +/- 0.19 (p < 0.01), and 3.92 +/- 0.33 (p < 0.001)
      micromol Pi x (mg protein)(-1) x min(-1), respectively). Activity of Na+/K+
      ATPase was increased by 800 ng/mL prolactin from 0.17 +/- 0.03 to 1.18 +/- 0.29
      micromol Pi x (mg protein)(-1) x min(-1) (p < 0.01). Prolactin at doses of 400
      and 600 ng/mL also significantly increased the activities of Ca(2+)-ATPase in
      crude homogenate from a control value of 0.84 +/- 0.03 to 1.75 +/- 0.29 (p <
      0.05), and 2.30 +/- 0.37 (p < 0.001) micromol Pi x (mg protein)(-1) x min(-1).
      When the crude homogenate was purified for the basolateral membrane, the
      Na(+)/K(+)-ATPase activities were elevated 10-fold. In the purified homogenate,
      800 ng/mL prolactin increased Na(+)/K(+)-ATPase activity from 1.79 +/- 0.38 to
      2.63 +/- 0.44 micromol Pi x (mg protein)(-1) x min(-1) (p < 0.05), and Ca(2+)
      ATPase activity from 0.08 +/- 0.14 to 2.03 +/- 0.23 micromol Pi x (mg protein)(
      1) x min-1 (p < 0.001). Because the apical calcium entry was the first important
      step for the transcellular active calcium transport, the brush border calcium
      uptake was also investigated in this study. We found that, 8 min after being
      directly exposed to 800 ng/mL prolactin, the brush border calcium uptake into the
      duodenal epithelial cells was increased from 0.31 +/- 0.02 to 0.80 +/- 0.28 nmol
      x (mg protein)(-1) (p < 0.05). It was concluded that prolactin directly and
      rapidly enhanced the brush border calcium uptake as well as the activities of the
      basolateral Na(+)/K(+)- and Ca(2+)-ATPases in the duodenal epithelium of female
      rats. These findings explained the mechanisms by which prolactin stimulated
      duodenal active calcium absorption.

PMID- 16902602
TI  - Long-duration freewheel running and submandibular lymphocyte response to forced
      exercise in older mice.
AB  - Submandibular lymph nodes (SLN) are crucial for immune surveillance of the
      anterior ocular chamber and upper respiratory tract; little is known about how
      training and exercise affect SLN lymphocytes. The intent of this study was to
      describe the impact of long term freewheel running followed by acute strenuous
      exercise on SLN lymphocytes in mice. Female C57BL/6 mice were assigned to running
      wheels or remained sedentary for 8 months, and further randomized to treadmill
      exercise and sacrifice immediately, treadmill exercise and sacrifice 24 h after
      exercise cessation, or no treadmill exposure. SLN lymphocytes were isolated and
      analyzed for CD3, CD4, CD8, and CD19 cell surface markers, phosphatidylserine
      externalization as a marker of apoptosis, and intracellular glutathione as a
      marker of oxidative stress. Compared with running wheel mice, older sedentary
      mice had a lower percent of T cells and higher percent of B cells (p < 0.05).
      Although intracellular glutathione did not differ between groups, running mice
      had a lower percent of Annexin V(+) SLN lymphocytes 24 h after treadmill
      exercise. Further research will be needed to determine if voluntary exercise
      translates into improved anterior ocular and upper respiratory tract health.

PMID- 16902603
TI  - Adenosine A1 receptor-mediated inhibition of myocardial norepinephrine release
      involves neither phospholipase C nor protein kinase C but does involve adenylyl
      cyclase.
AB  - Stimulation of adenosine A1 receptors in the heart exerts cardioprotective
      effects by inhibiting norepinephrine (NE) release from sympathetic nerve endings.
      The intraneuronal signal transduction triggered by presynaptic adenosine A1
      receptors is still not completely understood. The objective of the present study
      was to determine whether phospholipase C (PLC), protein kinase C (PKC), and
      adenylyl cyclase (AC) are involved in the adenosine A1 receptor-mediated
      inhibition of endogenous (stimulation-induced) NE release in isolated Langendorff
      perfused rat hearts as an approach to elucidate their role in the cardiovascular
      system. Activation of adenosine A1-receptors with 2-chloro-N6
      cyclopentyladenosine (CCPA) decreased cardiac NE release by approximately 40%.
      Inhibition of PLC with 1-[6-[[(17b)-3-methoxyestra-1,3,5(10)-trien-17
      yl]amino]hexyl]-1H-pyrrole-2,5-dione (U 73122) as well as inhibition of PKC with
      2-[1-(3-dimethylaminopropyl)indol-3-yl]-3-(indol-3-yl)maleimide (GF 109203X)
      slightly but significantly decreased NE release; however, the suppressive effect
      of CCPA on NE release was not modulated by U 73122 or GF 109203X. Blockade of AC
      with 9-(tetrahydro-2'-furyl)adenine (SQ 22536) reversed the inhibitory effect of
      CCPA on sympathetic neurotransmitter release irrespective of whether PKC was
      pharmacologically activated by phorbol 12-myristate 13-acetate or was not
      activated, indicating a PKC-independent but AC-dependent mechanism. Direct
      stimulation of AC with forskolin increased NE release by approximately 20%; an
      effect that was antagonized by either CCPA or SQ 22536. These data suggest that
      the adenosine A1 receptor-mediated inhibition of NE release does not involve PLC
      or PKC but does involve AC.

PMID- 16902604
TI  - Demonstration of fiber-laser-produced plasma source and application to efficient
      extreme UV light generation.
AB  - Efficient generation of extreme UV (EUV) light at lambda = 13.5 nm from a bulk Sn
      target has been demonstrated by using a fiber laser. The conversion efficiency
      from the 1064 nm IR to the EUV was measured to be around 0.9% into 2pi steradians
      within a 2% bandwidth. To the best of our knowledge, this is the first time an
      all-fiber system was used to generate EUV or soft x rays.

PMID- 16902605
TI  - Linear and angular coherence momenta in the classical second-order coherence
      theory of vector electromagnetic fields.
AB  - A new concept of vector and tensor densities is introduced into the general
      coherence theory of vector electromagnetic fields that is based on energy and
      energy-flow coherence tensors. Related coherence conservation laws are presented
      in the form of continuity equations that provide new insights into the
      propagation of second-order correlation tensors associated with stationary random
      classical electromagnetic fields.

PMID- 16902606
TI  - Vortex-bearing array of singular beams with very high orbital angular momentum.
AB  - We consider theoretically and experimentally an array of singular beams whose
      axes lie on the surface of a hyperboloid of revolution. We show that such a
      singular array can carry a very high orbital angular momentum. Experimental
      results demonstrate a way of generating such singular arrays.

PMID- 16902607
TI  - Distributed strain measurement with millimeter-order spatial resolution based on
      Brillouin optical correlation domain analysis.
AB  - Distributed strain sensing with millimeter-order spatial resolution is
      demonstrated in optical fibers based on Brillouin optical correlation domain
      analysis. A novel beat lock-in detection scheme is introduced to suppress
      background noises coming from the reflection of Brillouin pump waves. The
      Brillouin frequency shifts of 3 mm fiber sections are successfully measured with
      a theoretical spatial resolution of 1.6 mm.

PMID- 16902608
TI  - Optical fiber-based fluorescent viscosity sensor.
AB  - Molecular rotors are a unique group of viscosity-sensitive fluorescent probes.
      Several recent studies have shown their applicability as nonmechanical fluid
      viscosity sensors, particularly in biofluids containing proteins. To date,
      molecular rotors have had to be dissolved in the fluid for the measurement to be
      taken. We now show that molecular rotors may be covalently bound to a fiber-optic
      tip without loss of viscosity sensitivity. The optical fiber itself may be used
      as a light guide for emission light (external illumination of the tip) as well as
      for both emission and excitation light. Covalently bound molecular rotors exhibit
      a viscosity-dependent intensity increase similar to molecular rotors in solution.
      An optical fiber-based fluorescent viscosity sensor may be used in real-time
      measurement applications ranging from biomedical applications to the food
      industry.

PMID- 16902609
TI  - Anomalous dispersion in a solid, silica-based fiber.
AB  - We demonstrate an all-solid (nonholey), silica-based fiber with anomalous
      dispersion at wavelengths where silica material dispersion is negative. This is
      achieved by exploiting the enhanced dispersion engineering capabilities of higher
      order modes in a fiber, yielding + 60 ps/nm km dispersion at 1080 nm. By coupling
      to the desired higher-order mode with low-loss in-fiber gratings, we realize a 5
      m long fiber module with a 300 fs/nm dispersion that yields a 1 dB bandwidth of
      51 nm with an insertion loss of approximately 0.1 dB at the center wavelength of
      1080 nm. We demonstrate its functionality as a critical enabler for an all-fiber,
      Yb-based, mode-locked femtosecond ring laser.

PMID- 16902610
TI  - Optical label switching of DRZ/DPSK orthogonal signal generated by photonic
      crystal fiber.
AB  - We demonstrate orthogonal label switching by using a dark-return-to-zero (DRZ)
      payload and differential phase-shift keying (DPSK) label generated by a
      dispersion-flattened photonic-crystal fiber. The high extinction ratio of both
      the payload and label improves the receiver margin. The DRZ payload introduces
      little cross talk to the DPSK label due to the RZ-like output of the demodulated
      DPSK. Simulations are performed to study the eye-closure penalty of the payload
      and label at different DRZ pulse widths. We compare the DRZ/DPSK with the RZ and
      DPSK signals numerically at the same data rate and show that the DRZ/DPSK has a
      strong tolerance to the polarization-mode dispersion. The DRZ/DPSK has a more
      compact spectrum suitable for the strong filtering requirements in WDM systems.

PMID- 16902611
TI  - Low optical insertion-loss and vacuum-pressure all-fiber acetylene cell based on
      hollow-core photonic crystal fiber.
AB  - We report a novel and easy-to-implement hollow-core photonic crystal fiber cell
      fabrication technique based on helium diffusion through silica. The formed gas
      cells combine low optical insertion loss (1.8 dB) and vacuum acetylene pressure
      (microbar regime). The estimates of the final gas pressure, using both Voigt
      interpolation and electromagnetically induced transparency, show a good match
      with the initial fitting pressure.

PMID- 16902612
TI  - Brillouin characterization of holey optical fibers.
AB  - We report the results of detailed measurements on the Brillouin frequency shift
      (BFS), gain bandwidth, and gain coefficients of several small-core holey optical
      fibers (HFs) of both uniform and axially varying structural characteristics and
      compare these with measurements on more conventional fibers. Our measurements
      show that the BFS of HFs is first-order proportional to the modal index for light
      propagating along the fiber and is thus extremely sensitive to its precise
      structural parameters. Our results highlight the possibility of using distributed
      Brillouin scattering measurements to perform nondestructive structural
      characterization of HFs, and the possibility of producing Brillouin-suppressed
      HFs using controlled structural variation along the fiber length.

PMID- 16902613
TI  - Power-weighted dispersion distribution function for characterizing nonlinear
      properties of long-haul optical transmission links.
AB  - Based on the first-order perturbation theory, we introduce the power-weighted
      dispersion distribution (PWDD) function to characterize nonlinear properties of
      fiber-optic transmission links. This technique offers a new perspective on
      dispersion management for pseudolinear transmission. A rectangular PWDD model is
      used to describe the formation of ghost pulses analytically in the time domain
      without relying on the assumption that the pulse shape is Gaussian.

PMID- 16902614
TI  - All-fiber multimode interference bandpass filter.
AB  - A novel design for an all-fiber bandpass filter based on a multimode interference
      reimaging phenomenon is presented. The filter has achieved low insertion loss
      with adequate bandwidth and isolation for coarse wavelength-division
      multiplexing. The filter can easily be made with any central wavelength that is
      compatible with the single-mode fiber used for its construction. The measured
      filter performance matches the theoretical predictions well. The filter can have
      broad applications in fiber-optic telecommunications, spectroscopy, and sensing.

PMID- 16902615
TI  - Distributed suppression of stimulated Raman scattering in an Yb-doped filter
      fiber amplifier.
AB  - Suppression of stimulated Raman scattering (SRS) is demonstrated in a cladding
      pumped fiber amplifier. The Yb-doped amplifier fiber design incorporates a high
      index ring that resonantly couples SRS wavelengths out of the gain material, thus
      filtering the gain. Modeling shows that fiber asymmetry plays an important role
      in the filtering spectrum.

PMID- 16902616
TI  - Mid-infrared supercontinuum generation to 4.5 microm in ZBLAN fluoride fibers by
      nanosecond diode pumping.
AB  - A mid-infrared supercontinuum (SC) is generated in ZBLAN (ZrF4-BaF2-LaF3-AlF3
      NaF...) fluoride fibers from amplified nanosecond laser diode pulses with a
      continuous spectrum from approximately 0.8 microm to beyond 4.5 microm. The SC
      has an average power of approximately 23 mW, a pump-to-SC power conversion
      efficiency exceeding 50%, and a spectral power density of approximately -20
      dBm/nm over a large fraction of the spectrum. The SC generation is initiated by
      the breakup of nanosecond laser diode pulses into femtosecond pulses through
      modulation instability, and the spectrum is then broadened primarily through
      fiber nonlinearities in approximately 2-7 m lengths of ZBLAN fiber. The SC long
      wavelength edge is consistent with the intrinsic ZBLAN material absorption.

PMID- 16902617
TI  - Modal coupling in fiber tapers decorated with metallic surface gratings.
AB  - An interference-based scheme for fabricating periodic metal gratings on one side
      of the uniform waist of optical fiber tapers has been developed. Optical
      characterization of a 5 mm long, 511 nm period gold grating fiber taper with a 10
      microm diameter reveals backward coupling to both guided and radiation modes that
      is explained by using an analytical mode-coupling analysis. A refractometer based
      on this grating taper has a high and constant sensitivity over a large refractive
      index operating range of 1 to 1.41.

PMID- 16902618
TI  - Microchannels in conventional single-mode fibers.
AB  - Microchannels are fabricated into conventional single-mode fibers by femtosecond
      laser processing and chemical etching. Fabrication limitations imposed by the
      fiber geometry are highlighted and resolved through a simple technique without
      compromising fabrication flexibility. A microfluidic fiber device consisting of a
      4 microm wide microchannel that intersects the fiber core for refractive index
      sensing is further demonstrated.

PMID- 16902619
TI  - Optical encryption using phase-shifting interferometry in a joint transform
      correlator.
AB  - We propose an optical encryption technique where the encrypted field and the
      decrypting key are obtained by three-step phase-shifting interferometry and
      registered as digital Fresnel holograms in a joint transform correlator
      architecture. Decryption can be achieved by digital or optical means. The
      technique allows the complete process to be achieved at high speed and data to be
      transfered via digital communication channels. Experimental implementation is
      performed in a system based on a programmable liquid-crystal TV display working
      in pure phase mode to represent the input data and to introduce the required
      phase shifts. A CCD is used to register the output data.

PMID- 16902620
TI  - High-efficiency metal-semiconductor-metal photodetectors on heteroepitaxially
      grown Ge on Si.
AB  - We demonstrate extremely efficient germanium-on-silicon metal-semiconductor-metal
      photodetectors with responsivities (R) as high as 0.85 A/W at 1.55 microm and 2V
      reverse bias. Ge was directly grown on Si by using a novel heteroepitaxial growth
      technique, which uses multisteps of growth and hydrogen annealing to reduce
      surface roughness and threading dislocations that form due to the 4.2% lattice
      mismatch. Photodiodes on such layers exhibit reverse dark currents of 100 mA/cm2
      and external quantum efficiency up to 68%. This technology is promising to
      realize monolithically integrated optoelectronics.

PMID- 16902621
TI  - Minimizing finite-size effects in artificial resonance tunneling structures.
AB  - We consider finite-size effects in coupled cavity structures. Starting with
      microring resonator structures well described by transfer matrices, we obtain
      conditions that lead to the minimization of finite-size effects. Our approach
      does not require numerical optimization and requires only slight modification of
      design parameters guided by closed-form analytical expressions. Using a Breit
      Wigner scattering formalism, we demonstrate that the scheme can be used to
      minimize finite-size effects in a general class of coupled cavity structures. The
      strength of the present technique lies in its simplicity and its applicability to
      a wide variety of structures described by tight-binding formalisms.

PMID- 16902622
TI  - Multistage high-order microring-resonator add-drop filters.
AB  - We propose and demonstrate a multistage design for microphotonic add-drop filters
      that provides reduced drop-port loss and relaxed tolerances for achieving high in
      band extinction. As a result, the first microring-resonator filters with a
      rectangular notch stopband in the through port (to our knowledge) are shown, with
      extinctions exceeding 50 dB. Reaching 30 dB beyond previous results, without
      postfabrication trimming, such extinction levels open the door to microphotonic
      notch circuits for spectroscopy, wavelength conversion, and quantum cryptography
      applications. Combined with a low-loss, high-index-contrast electromagnetic
      design in SiN and frequency-matched microring resonators, this approach led to
      the first demonstration of flattop microphotonic filters meeting the stringent
      criteria for high-spectral-efficiency integrated add-drop multiplexers. The 40
      GHz wide filters show a 20 nm free spectral range, 2 dB drop loss, and
      suppression of adjacent channels by over 30 dB.

PMID- 16902623
TI  - Measurements of the alpha factor of a distributed-feedback quantum cascade laser
      by an optical feedback self-mixing technique.
AB  - We demonstrate measurements of the alpha factor of a distributed-feedback quantum
      cascade laser (QCL) by using a newly modified self-mixing interferometric
      technique exploring the laser itself as the detector. We find a strong dependence
      of the alpha factor on the injection current, ranging from -0.44 at 120 mA to
      2.29 at 180 mA, which can be attributed to the inherent physics of QCLs.

PMID- 16902624
TI  - Phase locking and in-phase supermode selection in monolithic multicore fiber
      lasers.
AB  - We report a compact multicore fiber laser that utilizes an all-fiber approach for
      phase locking and in-phase supermode selection. By splicing passive coreless
      fibers of controlled lengths to both ends of an active 19-core fiber, we
      demonstrate that the fundamental in-phase supermode can be selectively excited
      with a completely monolithic fiber device, instead of conventional free-space and
      bulk optics, to achieve phase-locked operation for a multiemitter laser device.

PMID- 16902625
TI  - Characteristics of a continuous-wave Yb:GdVO4 laser end pumped by a high-power
      diode.
AB  - An efficient and compact diode-pumped continuous-wave Yb:GdVO4 laser is
      demonstrated, generating an output power of 4.0 W with an optical conversion
      efficiency of 61% and a slope efficiency as high as 78%. With increasing pump
      power the polarization of the laser output changes from sigma to pi, while in a
      certain intermediate power range the two polarization states coexist with
      different emission wavelengths.

PMID- 16902626
TI  - Localized vibrational modes in optically bound structures.
AB  - We show, through analytical theory and rigorous numerical calculations, that
      optical binding can organize a collection of particles into extended, periodic
      one-dimensional lattices. These lattices, as well as other optically bound
      structures, are shown to exhibit spatially localized vibrational eigenmodes. The
      origin of localization here is distinct from the usual mechanisms such as
      disorder, defect, or nonlinearity but is a consequence of the long-ranged nature
      of optical binding. For an array of particles trapped by an interference pattern,
      the stable configuration is often dictated by the external light source, but we
      observed that interparticle optical binding forces can have a profound influence
      on the dynamics.

PMID- 16902627
TI  - Tunable single-mode Fabry-Perot laser diode using a built-in external cavity and
      its modulation characteristics.
AB  - A tunable single-mode laser is obtained by using a weakly coupled cavity
      structure involved in a coaxially packaged Fabry-Perot laser diode. The cleaved
      end facet of the coupling fiber becomes an optical reflector and forms an
      external cavity with a laser facet. The single-mode oscillation condition is
      controlled and stabilized by tuning the operating temperature. The tuning range
      is about 10 nm with the side-mode suppression ratio of more than 27 dB when the
      temperature changes from 11.5 degrees C to 25 degrees C. Direct modulation
      characteristics were investigated, and our results show that a shorter external
      cavity can bear deeper modulation depth.

PMID- 16902628
TI  - Analytical solutions for the electromagnetic fields of tightly focused laser
      beams of arbitrary pulse length.
AB  - The analytical solution for a monochromatic focused laser beam was recently
      published [Opt. Lett.31, 1447 (2006)]. The effect of introducing bandwidth by
      including a finite-length temporal pulse envelope is included exactly. This is
      done formally first in the frequency domain for an arbitrary pulse shape, and the
      specific case of a cosine-squared envelope is then solved analytically for all
      pulse lengths, thereby decreasing the computation time by 2 orders of magnitude.
      The inclusion of longer wavelengths reduces the fraction of laser energy in the
      focus from 86.5% to 83.5% for a 5 fs Ti:sapphire laser and 72.7% in a single
      cycle pulse.

PMID- 16902629
TI  - Nanosphere dispersed liquid crystals for tunable negative-zero-positive index of
      refraction in the optical and terahertz regimes.
AB  - An analysis of aligned nematic liquid crystal cells containing core-shell
      nanospheres shows that it is possible to devise a new type of metamaterial whose
      index of refraction is tunable from negative, through zero, to positive values.
      The design parameters for the constituents can be scaled for application in the
      optical as well as very long wavelength (e.g., terahertz and microwave) regions.

PMID- 16902630
TI  - Lattice-supported surface solitons in nonlocal nonlinear media.
AB  - We reveal that lattice interfaces imprinted in nonlocal nonlinear media support
      surface solitons that do not exist in other similar settings, including
      interfaces of local and nonlocal uniform materials. We show the impact of
      nonlocality on the domains of existence and stability of the surface solitons,
      focusing on new types of dipole solitons residing partially inside the optical
      lattice. We find that such solitons feature strongly asymmetric shapes and that
      they are stable in large parts of their existence domain.

PMID- 16902631
TI  - Copropagating superluminal and slow light manifested by electromagnetically
      assisted nonlinear optical processes.
AB  - We report an experimental observation of nonlinear optical gain and loss assisted
      by electromagnetically induced transparency (EIT) and simultaneous superluminal
      and subluminal light propagations. Two circular components of a linearly
      polarized light initiate third-order nonlinear processes in which one circular
      component is attenuated while the other component is amplified in a three-level
      EIT system. Near the atomic resonance, the attenuated circular component
      experiences steep normal dispersion and propagates with a slow group velocity,
      while the amplified circular component experiences steep anomalous dispersion and
      propagates with a superluminal group velocity.

PMID- 16902632
TI  - Spatial mode cleaning by femtosecond filamentation in air.
AB  - By studying the conical emission of a blue femtosecond laser filament in air, it
      is shown that self-improvement of the beams' spatial mode quality occurs for a
      self-guided laser pulse.

PMID- 16902633
TI  - Raman-resonance-enhanced composite nonlinearity of air-guided modes in hollow
      photonic-crystal fibers.
AB  - Coherent anti-Stokes Raman scattering (CARS) is used to measure relations between
      the resonant (Raman) and nonresonant (Kerr-type) optical nonlinearities of air
      guided modes in a hollow-core photonic-crystal fiber (PCF). We demonstrate that,
      due to its interference nature, CARS provides a convenient tool for measuring the
      contribution of the fiber cladding to the total nonlinearity sensed by air-guided
      modes in hollow PCFs. On a Raman resonance with molecular vibrations in the gas
      that fills the fiber core, a two-color laser field is shown to induce optical
      nonlinearities that are several orders of magnitude higher than the nonresonant
      Kerr-type nonlinearities typical of air-guided PCF modes.

PMID- 16902634
TI  - Coaxial holographic data storage without recording the dc components.
AB  - A technique of recovering the data pages from Fourier holograms recorded without
      the dc components is demonstrated theoretically and experimentally by use of a
      coaxial holographic storage system. A reconstructed image is obtained by adding a
      phase-modulated dc component of the signal beam on reading. The bit error rate of
      the reconstructed image is comparable with that for the hologram recorded with
      the dc component as well. Since high intensities of the dc components are not
      recorded in this technique, the dynamic range of the recording media can be
      saved, which potentially contributes to increasing the number of multiplexed
      holograms.

PMID- 16902635
TI  - Polymeric, electrically tunable diffraction grating based on artificial muscles.
AB  - We demonstrate a low-cost, electrically tunable diffraction grating that is
      driven by a dielectric elastomer actuator. The angular tuning range of the
      polymer-based device is up to 118 mrad for the first diffracted order. The
      achievable grating period change of 32% is an improvement by more than a factor
      of 150 compared with existing analog tunable diffraction gratings based on hard
      materials. We show that in combination with a white light source, the presented
      diffraction grating can be used as a wavelength-adjustable luminous source. Such
      an illuminant has a potential application in inexpensive color displays that
      could reproduce all perceivable colors.

PMID- 16902636
TI  - Large-area surface-plasmon polariton interference lithography.
AB  - Large-area surface-plasmon polariton (SPP) interference lithography is presented,
      which uses an attenuated total reflection-coupling mode to excite the
      interference of the SPPs. The interference of the SPPs causes a highly
      directional intensity range in a finite depth of the electric field, which is
      good for noncontact. Finite-difference time-domain simulations of the
      interference on a thin resist layer show that broad-beam illumination with a p
      polarized light at a wavelength of 441 nm can produce features as small as 60 nm
      with high contrast, smaller than lambda/7. Our results illustrate the potential
      for patterning periodic structures over large areas at low cost.

PMID- 16902637
TI  - Analytical vectorial structure of Laguerre-Gaussian beam in the far field.
AB  - Based on the vector angular spectrum of the electromagnetic beam and the method
      of stationary phase, the analytical vectorial structure of the Laguerre-Gaussian
      beam has been presented in the far field. According to the analytical
      electromagnetic representations of the TE and TM terms, the energy flux
      distributions of the TE term, the TM term, and the whole beam are investigated in
      the far field, respectively. The formulas obtained are applicable not only to the
      paraxial case, but also to the nonparaxial case. The physical pictures of
      Laguerre-Gaussian beams are well illustrated from the vectorial structure, which
      may provide a new approach to manipulate laser beams.

PMID- 16902638
TI  - Fields of a radially polarized Gaussian laser beam beyond the paraxial
      approximation.
AB  - Analytic expressions for the fields of a tightly focused radially polarized
      Gaussian laser beam are derived, accurate to epsilon5, where epsilon is the
      associated diffraction angle. The fields satisfy Maxwell's equations, and the
      calculated beam power based on them is significantly different from that of the
      paraxial-approximation fields.

PMID- 16902639
TI  - Collins diffraction formula studied in quantum optics.
AB  - We find that the Collins diffraction formula in cylindrical coordinates is just
      the transformation matrix element of a three-parameter two-mode squeezing
      operator in the deduced entangled state representation. This is a new tie
      connecting the unitary transform in quantum optics to the generalized Hankel
      transform in Fourier optics. The group multiplication rule of the squeezing
      operators maps to the Collins formula related to two successive Hankel
      transforms.

PMID- 16902640
TI  - Decoherence of electromagnetically induced transparency in atomic vapor.
AB  - We report characterization of electromagnetically induced transparency (EIT)
      resonances in the D1 line of (87)Rb under various experimental conditions. The
      dependence of the EIT linewidth on the power of the pump field was investigated
      at various temperatures for the ground states of the lambda system associated
      with different hyperfine levels of the atomic 5S(1/2) state as well as magnetic
      sublevels of the same hyperfine level. Strictly linear behavior was observed in
      all cases. A theoretical analysis of our results shows that dephasing in the
      ground state is the main source of decoherence, with population exchange playing
      a minor role.

PMID- 16902641
TI  - Nonunity gain quantum nondemolition measurements based on measurement and
      repreparation.
AB  - We demonstrate experimentally a nonunity gain quantum nondemolition measurement
      based on a simple homodyne measurement and recreation strategy. Although the
      output state is an amplified version of the input state, the device meets
      standard criteria for QND measurements: the transfer coefficient was measured to
      1.78, and the conditional variance was measured to 0.66.

PMID- 16902642
TI  - High spatiotemporal resolution in multifocal processing with femtosecond laser
      pulses.
AB  - We report spatial and temporal dispersion compensation for fan-out of femtosecond
      pulses with a low-frequency diffraction grating by means of a hybrid diffractive
      refractive lens triplet. In this way, we achieve a multifocal light structure
      with nearly diffraction-limited light spots even for 20 fs pulse duration. The
      spatial chromatic compensation, which drastically reduces the lateral walk-off of
      the various spectral components, also allows us to improve the available
      bandwidth at the dispersion-compensated diffraction orders. In fact, the temporal
      width of the output pulse is essentially limited by the group-delay dispersion
      term, which is shown to be small. The high spatiotemporal resolution provided by
      our proposal permits parallel multifocal processing of materials with femtosecond
      pulses.

PMID- 16902643
TI  - Piston measurement by quadriwave lateral shearing interferometry.
AB  - We present what is to our knowledge a new method for measuring the relative
      piston between two independent beams separated by a physical gap, typical of
      petawatt facilities. The feasibility of this measurement, based on quadriwave
      lateral shearing interferometry, has been demonstrated experimentally: piston has
      been measured with accuracy and sensitivity better than 50 nm.

PMID- 16902644
TI  - Effect of dielectric properties of metals on terahertz transmission subwavelength
      hole arrays.
AB  - We study the influence of dielectric function of metals on the transmission
      properties of terahertz pulses through periodically patterned subwavelength
      holes. Because of a drastic increase in the value of dielectric constants, most
      metals become highly conductive at terahertz frequencies. Extraordinary terahertz
      transmission is observed in subwavelength hole arrays made from both good and
      poor electrical conductors. The measured transmittance of terahertz pulses is
      found to be enhanced with increasing ratio of the real to the imaginary
      dielectric constant of the constituent metals, for which the dielectric function
      follows the Drude model.

PMID- 16902645
TI  - Interplay of nonlinearity and gain shaping in femtosecond fiber amplifiers.
AB  - A study of chirped-pulse amplification in the presence of large nonlinear phase
      shifts (as large as approximately 12pi) and finite gain bandwidth is presented.
      Numerical simulations that include the effect of nonlinearity, group-velocity
      dispersion, higher-order dispersion, and finite gain bandwidth predict the
      spectral signature of the interplay of nonlinearity with gain shaping.
      Experimental results obtained for up to approximately 0.4 microJ pulse energies
      from a Yb fiber amplifier agree with the numerical calculations.

PMID- 16902646
TI  - Nature of subpicosecond terahertz pulse propagation in practical dielectric
      filled parallel-plate waveguides.
AB  - It is analytically shown that the presence of submicrometer-sized air gaps
      between the dielectric and metal contact surfaces in a dielectric-filled metallic
      parallel-plate waveguide can have a dramatic effect on the guided-wave
      propagation of subpicosecond terahertz pulses. Through the use of metal
      evaporated dielectric surfaces to overcome the imperfect contact problem, and a
      special air-dielectric-air cascaded waveguide geometry to avoid multimode
      excitation, undistorted subpicosecond terahertz pulse propagation via the single
      TEM mode is demonstrated, for what is believed to be the first time, in a silicon
      filled PPWG.

PMID- 16902647
TI  - Estimation-induced correlations of the Zernike coefficients of the eye
      aberration.
AB  - The statistical properties of the estimated eye aberrations differ in general
      from the actual ones owing to the cross coupling and aliasing generated in the
      estimation process. In particular, the estimated Zernike aberration coefficients
      may show fictitious correlations that are not present in the incoming wavefronts.
      This fact should be taken into account when analyzing estimated aberration
      datasets, searching for correlations related to physiological eye features. We
      give an analytical model for this effect and evaluate its magnitude for a
      particular example, assuming that the true aberration statistics follows a
      Kolmogorov power law.

PMID- 16902648
TI  - Pain physician continues to progress towards excellence.

PMID- 16902649
TI  - Prevalence of cervical facet joint pain in chronic neck pain.
AB  - Neck pain is considered to be one of the most common chronic pain conditions in
      modern society. Various structures identified as capable of transmitting pain in
      the cervical spine include facet joints, intervertebral discs, nerve root dura,
      ligaments, fascia, and muscles. The prevalence of cervical facet joint pain in
      patients with chronic pain after whiplash has been determined as 54% to 60%.
      However, the prevalence of chronic cervical facet joint pain has not yet been
      determined in a heterogenous population or in patients with cervical spine pain
      of idiopathic origin in a controlled environment. This study evaluated 160
      patients seen in one interventional pain management practice in a non-university
      setting. Cervical facet joints were investigated with diagnostic blocks using
      lidocaine 1% preservative free initially, followed by bupivacaine 0.25%, usually
      2 to 4 weeks apart. The study population consisted of 76 women and 30 men aged 43
      +/- 13 years of age (mean +/- SD). Mode of onset of neck pain was determined as
      following a traumatic incident in 48% of the patients, whereas it was with
      gradual onset without an identifiable specific incident in the remaining 55
      patients (52%). Eighty-one or 70% of the patients (70%) reported a definite
      response to lidocaine blocks. Confirmatory blocks with bupivacaine were performed
      in 81 patients with 64 patients with 60% of the total sample, or 79%, of the
      lidocaine-positive group reporting definite response with improvement in their
      pain. Thus, a prevalence rate of facet joint pain in chronic neck pain was
      determined to be 60% (95% CI, 50%-70%), with a false positive rate of controlled
      diagnostic blocks of 40% (95% CI, 34%-46%).

PMID- 16902650
TI  - Percutaneous disc decompression using coblation (nucleoplasty) in the treatment
      of chronic discogenic pain.
AB  - Clinical outcome data was analyzed for 67 patients with contained disc herniation
      who underwent percutaneous disc decompression procedure using Coblation(R)
      technology, also referred to as Nucleoplasty after failing to respond to
      conservative management. Patients presented with clinical symptoms of discogenic
      low back pain and/or leg pain and were not considered candidates for open
      surgery. Follow-up data was collected up to 12 months. Patient gender
      distribution was 70% female, 30% male, with a mean age of 44 years. The onset of
      the pain was predominantly of nontraumatic origin with an average duration of
      pain of 5.4 years ranging from 4 months to 29 years with history of previous
      surgical intervention in 13% of the patients. At 1 year, 80% of the patients
      demonstrated statistically significant improvement in numeric pain scores.
      Average pre-procedure pain level for all patients was reported as 6.8 while
      average pain level was 4.1 at the 12 month follow-up period. Statistically
      significant improvement was observed in 62%, 59%, and 60% of patients in sitting,
      standing, and walking ability at 12 months, respectively. The results of this
      analysis indicated that PDD using Coblation technology, also referred to as
      Nucleoplasty, is an effective procedure for patients presenting with discogenic
      back and/or leg pain who have failed conservative therapies and are not
      considered candidates for open surgical interventions.

PMID- 16902651
TI  - Clinical evidence of chemical radiculopathy.
AB  - It is universally accepted that an anatomic abnormality such as a herniated disc
      or spinal stenosis can lead to radicular leg pain. There is some controversy as
      to whether radicular pain can be caused by a non-structural, solely biochemical
      disorder. Prior studies using biochemical analysis of inflammatory mediators of
      the disc or surrounding structures have enumerated many possible biochemical
      mediators of radicular pain. However, such studies have not definitively
      demonstrated whether these inflammatory mediators are the causes of radicular
      pain or whether these mediators are simply products of the degenerative cascade.
      The purpose of this paper is to report upon patients who satisfy strict criteria
      affirming a diagnosis of radiculopathy in the presence of normal imaging studies.
      The study was designed as a prospective case series of patients fulfilling
      inclusion and exclusion criteria at a university hospital outpatient physiatric
      spine practice. Inclusion criteria consisted of symptoms of extremity pain
      greater than axial pain, examination findings demonstrating a new myotomal
      deficit that correlates with the root level predicted by the dermatomal pain
      distribution, and failure to improve after at least 4 weeks of active physical
      therapy. Magnetic resonance imaging void of local nerve root pathology as per
      review by the first author and the interpreting radiologist was required. Each
      patient had to have a positive electromyographic study for an acute
      radiculopathy. Each patient had to have a positive fluoroscopically guided
      diagnostic selective nerve root block. In summary, this paper provides clinical
      evidence that anatomic abnormalities are not required to cause radiculopathy,
      thus implying that a biochemical etiology is likely to play a significant role in
      radiculopathy and radicular pain.

PMID- 16902652
TI  - Effectiveness of transforaminal epidural steroid injections in low back pain: a
      one year experience.
AB  - Transforaminal epidural steroid injections under fluoroscopy are an alternative
      treatment for lower back pain with radiculopathy. We followed 82 patients with a
      standardized telephone questionnaire at 2, 6, and 12 months after the first
      injection, in order to assess their effectiveness. Ninety-two patients with
      radiculopathic back pain due to spinal stenosis, herniated discs,
      spondylolisthesis, and degenerated discs, underwent transforaminal epidural
      steroid injections under fluoroscopy. Eighty-two patients were followed with a
      standardized telephone questionnaire. The population was divided into four
      groups: Group I, previous back surgery (16%); Group II, discogenic abnormalities:
      herniations, bulges, or degeneration, (42%); Group III, spinal stenosis (32%);
      Group IV, those without MRI (11%). Age ranged between 24 to 99 years, mean 64.5.
      Forty-seven were female, 35 male. Thirteen patients (16%) underwent one
      procedure, 27 patients (33%) two, 37 patients (45%) three, and five patients (6%)
      four, an average 2.4 procedures per patient. The pain scores for all patients
      improved significantly at all three time points (2, 6 and 12 months) compared to
      the initial mean pain score of 7.3 to mean pain scores of 3.4, 4.5 and 3.9
      respectively. After one year, 36 patients did not take any pain medications.
      Greater than 50% improvement after one year was seen in 23% of Group I; 59% in
      Group II; 35% in Group III and 67% in Group IV. Transforaminal epidural steroid
      injections can offer significant pain reduction up to one year after initiation
      of treatment in patients with discogenic pain and possibly in patients with
      spinal stenosis.

PMID- 16902653
TI  - Did this patient have lumbar fusion? Review of MRI findings.

PMID- 16902654
TI  - Research designs in interventional pain management: is randomization superior,
      desirable or essential?
AB  - In the hierarchy of research designs, the results of randomized, controlled
      trials are considered to be evidence of the highest grade, whereas observational
      studies are viewed as having less validity because they reportedly overestimate
      treatment effects. This hierarchy approach to study design has been promoted
      widely in modern medical literature; in spite of overwhelming evidence that
      evidence-based medicine includes all types of evidence, and randomized, double
      blind studies should not necessarily be considered to represent the best
      available evidence. In fact, randomized, double-blind studies face insurmountable
      challenges in interventional pain management. The value of the so-called gold
      standard of randomized, double-blind trials has been questioned. This study was
      undertaken to evaluate if randomization does provide the protective statistical
      shield that some think it provides in an interventional pain management
      population. In this study we compared randomized and non-randomized samples.
      Randomization was accomplished by the use of random number tables and random
      sampling into four groups, three or two groups. Non-randomization was achieved by
      allocation into various groups by two different means. The results of this
      evaluation showed that there was only one significant difference when patients
      were allocated by means of non-randomization among the groups or compared to the
      total sample. In contrast, randomization showed significant differences in seven
      parameters. The results of this study conclude that in interventional pain
      management settings, non-randomized sampling is valid.

PMID- 16902655
TI  - No clear winner in differing imaging modalities for cervical radiculopathy.
AB  - We review the literature pertaining to the strengths and limitation of
      myelography, computerized tomography (CT) and magnetic resonance imaging (MRI)
      relative to developing a diagnostic algorithm in the evaluation of cervical
      radiculopathy. To obtain the relevant literature, a Medline search was conducted
      using selected keywords and phrases. In addition, the bibliography of all
      retrieved articles was searched and pertinent articles were obtained and
      evaluated. The analysis revealed that developing a research based algorithm of
      imaging studies for the evaluation of cervical radiculopathy is not currently
      realistic. Furthermore, we found that most studies on the predictive value of
      imaging studies for cervical radiculopathy are outdated by more recent
      technology.

PMID- 16902656
TI  - Vascular supply to the lumbar spine: an intimate look at the lumbosacral nerve
      roots.
AB  - The vascular supply of the lumbar vertebral column is a diverse collection of
      arteries originating from both central and peripheral sites. Until recently, the
      majority of these studies have been dedicated to the blood supply of the spinal
      cord and vertebral bodies. More recent effort has been directed toward the
      identification of the vascular supply to the lumbar nerve roots. These studies
      have conclusively documented the presence of a dual blood supply to the nerve
      roots. In addition, this dual vascular supply has been discovered to have the
      capability for bi-directional flow. This unique property may allow for prevention
      of localized, compressive ischemic symptoms secondary to either herniated disc
      material or osteophytes. The nutrient contributions of the cerebrospinal fluid
      and venous supply to nerve roots have also been investigated. Early studies
      indicate that they may play a greater role than suspected. The presence of
      multiple sources of nutrient supply to the lumbar nerve roots enables them to be
      resistant to the potential compressive phenomenon that may occur in the lumbar
      spine.

PMID- 16902657
TI  - National All Schedules Prescription Electronic Reporting Act (NASPER): balancing
      substance abuse and medical necessity.
AB  - The National All Schedules Prescription Electronic Reporting Act, or NASPER, is a
      bill proposed by the American Society of Interventional Pain Physicians to
      provide and improve patient access with quality care, and protect patients and
      physicians from deleterious effects of controlled substance misuse, abuse and
      trafficking. Controlled prescription drugs, including narcotic analgesics,
      anxiolytics, anti-depressants, stimulants, and sedative-hypnotics play a
      significant and legitimate role in interventional pain management practices in
      managing chronic pain and related disorders. Based on the 1997 household survey
      on drug abuse it is estimated that 76.9 million Americans had used an illicit
      drug at least once in their life. In 1997, 4.2 million people used analgesics,
      2.1 million used tranquillizers, and an additional 2.3 million people used
      various other drugs, including sedatives, tranquillizers, etc. The non-medical
      use of prescription drugs exceeds that of all illicit substances except for
      marijuana and hashish. The report on epidemiology trends in drug abuse, based on
      community epidemiology work group analysis showed continued increase of abuse of
      prescription drugs in urban, suburban, and rural areas. The most commonly abused
      drugs include oxycodone, hydrocodone, hydromorphone, morphine, codeine,
      clonazepam, alprazolam, lorazepam, diazepam and carisoprodol. The diversion of
      prescription controlled substances to illicit channels is a public health and
      safety issue. This review describes the role of controlled substances in chronic
      pain management, prevalence and economic impact of controlled substance abuse,
      prescription accountability, effectiveness of prescription monitoring programs,
      and rationale for national controlled substance electronic reporting system.

PMID- 16902658
TI  - Implications of fraud and abuse in interventional pain management.
AB  - The federal government has enacted a comprehensive strategy to fight healthcare
      waste, fraud and abuse. As a result of the federal government's comprehensive
      strategy, in 2002, the Office of Inspector General announced that improper
      Medicare payments to doctors, hospitals and other healthcare providers declined
      54% from the fiscal year 1996 to the fiscal year 2001. The Office of Inspector
      General in its 2002 work plan focuses on procedure coding for outpatient services
      billed by hospital and doctor, coding for evaluation and management services in
      physician offices and conditions under which a doctor's bill is "incident to"
      services or supplies among other things. The distinction between fraud and abuse
      can be very important in determining the potential fines and penalties that might
      apply, even though it is not clear. Fraud is much more serious than abuse. The
      degree of intent by the individual or entity under investigation is often the
      determining factor. The most commonly used statutes for prosecuting or
      facilitating such a prosecution of healthcare fraud or abuse include HIPAA of
      1996, the False Claims Act, healthcare fraud, theft or embezzlement, obstruction
      of criminal investigations of healthcare offenders, the False Statement Statute,
      mail and wire fraud statutes, the Social Security Act Civil Monetary Penalties,
      criminal penalties, and/or Stark laws. This review focuses on various aspects of
      implications of fraud and abuse in interventional pain management practices
      including various activities of potential fraud and abuse.

PMID- 16902660
TI  - Pain and emotional status.

PMID- 16902661
TI  - Pain physician embraces the future.

PMID- 16902662
TI  - Percutaneous disc decompression using nucleoplasty.
AB  - The objective of this study was to evaluate the effectiveness of Nucleoplasty for
      decompression of contained herniated discs, in a prospective, single site study
      that evaluated 49 consecutive patients with complaints of back with or without
      leg pain secondary to a contained focal protrusion. Access to the disc was
      obtained via the posterolateral discography approach, with a 17-gauge introducer
      needle inserted through the annulus and into the nucleus. The introducer remained
      in place within the outer annulus during the entire procedure, providing access
      for the SpineWand into the nucleus. The procedure was performed on an outpatient
      basis. One month, three month, six-month and twelve month outcomes were assessed
      by the treating physician and support staff. Success was defined as a minimum 2
      point reduction on a Visual Analog Scale (VAS), patient satisfaction, absence of
      narcotic use, and return to work if not working secondary to back pain. The pre
      procedure and post-procedure VAS differences were 4.28 (p<0.001), 4.66 (p<0.001),
      4.75 (p<0.001), and 3.3 (p=0.002) at the one month, 3 month, 6 month, and 12
      month intervals respectively. Overall, there was a 79% success rate, with 67%
      success in the group of patients that had previous surgery and 82% success in the
      group that had no prior surgical intervention. Results indicate that Nucleoplasty
      may be a promising and efficacious minimally invasive procedure for the treatment
      of symptoms associated with contained herniated discs. Randomized, controlled
      studies with subgroup analysis are required to further delineate the role for
      this procedure.

PMID- 16902663
TI  - Effectiveness of clinical guidelines in interventional pain management.
AB  - Many commissions and groups throughout the world have proposed clinical
      guidelines on the management of low back pain, spinal pain, and chronic pain.
      Practice guidelines are systematically developed statements to assist the
      practitioner and patient decisions about appropriate healthcare for specific
      clinical circumstances. The American Society of Interventional Pain Physicians
      developed practice guidelines for interventional techniques which are
      professional practice recommendations for practices for prevention, diagnosis and
      treatment of acute and chronic painful disorders, and in some cases, disability
      management. The effectiveness of so-called evidence-based guidelines has not
      proven. This study was designed to evaluate a total of 300 patients with 100
      randomized patients seen in the month of January 1999, 2000 and 2001, in one
      private pain management practice in a non-university setting. The study was
      retrospective for 1999 and 2000, whereas it was prospective for 2001. The results
      showed that there were no significant differences in patient demographics or
      their psychological status. The results consistently showed decrease in number of
      visits from 1999 to 2000 and 2001 with 5.5 +/- 0.18, 5.1 +/- 0.17, and 4.3 +/-
      0.15 respectively. The average expenditure also decreased from per visit of $872
      in 1999 to $891 in 2000, to $810 to 2001. further, the average expenditure per
      year also decreased as expected due to decrease in frequency of visits, as well
      as the average expenditure per visit from $4751 +/- $231 in 1999 to $4505 +/-
      $214 in 2000 and to $3514 +/- $193 in 2001 even without consideration of
      inflation. Thus, it is concluded that guidelines describing the interventional
      techniques in the management of chronic pain are effective in reducing the cost
      and frequency of visits with improvement or at least maintenance of similar
      outcomes, physician decision making abilities, and patient preferences.

PMID- 16902664
TI  - Role of caudal epidural injections in the management of chronic low back pain.
AB  - Caudal epidural administration of corticosteroids is one of the commonly used
      interventions in managing chronic low back pain. Reports of the effectiveness of
      all types of epidural steroids have varied from 18% to 90%. Sicard, a
      radiologist, was the first to describe injection of dilute solutions of cocaine
      through the sacral hiatus into the epidural space in 1901, to treat patients
      suffering from severe, intractable sciatic pain or lumbago. This was followed by
      an explosion of reports and evolving interest in caudal epidural steroids with
      two additional reports in 1901 and numerous other reports over the years. The
      philosophy of epidural steroid injections is based on the premise that the
      corticosteroid delivered into the epidural space attains higher local
      concentrations over an inflamed nerve root and will be more effective than a
      steroid administered either orally or by intramuscular injection. The clinical
      effectiveness evaluations fill the literature with various types of reports
      including randomized clinical trials, prospective trials, retrospective studies,
      case reports, and meta-analyses. Evidence from all types of evaluations with
      regards to the clinical and cost-effectiveness of caudal epidural injections is
      encouraging. This review discusses various aspects of the role of caudal epidural
      injections in the management of chronic low back pain, including pathophysiology
      of low back pain, indications, clinical effectiveness and complications.

PMID- 16902665
TI  - Evaluation of psychological status in chronic low back pain: comparison with
      general population.
AB  - Multiple studies have documented a strong association between chronic low back
      pain and psychopathology including personality disorders, depressive disorders,
      anxiety, and somatoform disorders along with non-specific issues such as emotion,
      anger and drug dependency. However, depression, anxiety and somatization appear
      to be crucial. There are no controlled trials in interventional pain management
      settings. This study was designed to evaluate 40 individuals without pain or
      psychotherapeutic drug therapy, Group I, control group; and Group II, chronic low
      back pain group with 40 chronic low back pain patients. All the participants were
      tested utilizing Pain Patient Profile (P3). Significant differences were found
      among various clinical syndromes with generalized anxiety disorder, somatoform
      disorder, and depression, with 0% vs 20%, 0% vs 20%, and 5% vs 30% in Group I and
      Group II consecutively. This evaluation showed that clinical syndromes were seen
      in a greater proportion of patients with chronic low back pain emphasizing the
      importance of evaluation of the patients for generalized anxiety disorder,
      somatoform disorder, and for depression.

PMID- 16902666
TI  - Spinal cord stimulation.
AB  - Spinal cord stimulation is the most common mode of neuromodulation used in
      managing chronic low back pain. It is minimally invasive and reversible as
      opposed to nerve ablation. The basic scientific background of the initial spinal
      cord stimulation trials was based on the gate control theory of Melzack and Wall.
      It has been demonstrated in multiple studies that dorsal horn neuronal activity
      caused by peripheral noxious stimuli could be inhibited by concomitant
      stimulation of the dorsal columns. Various other mechanisms, which may play a
      significant role in the mechanism of action of spinal cord stimulation, include
      the suppressive effect of spinal cord stimulation on tactile allodynia, increased
      dorsal horn inhibitory action of gamma-aminobutyric acid (GABA), prevention or
      abolition of peripheral ischemia, and effects on human brain activity. Spinal
      cord stimulation is indicated in low back pain with radiculopathy, failed back
      surgery syndrome, complex regional pain syndrome, peripheral vascular disease,
      and ischemic heart disease. There is substantial scientific evidence on the
      efficacy of spinal cord stimulation for treatment of low back and lower extremity
      pain of neuropathic nature. Clinical studies revealed a success rate of from 50%
      to 70% with spinal cord stimulation, with decreased pain intensity scores,
      functional improvement and decreased medication usage. This review discusses
      multiple aspects of spinal cord stimulation, including pathophysiology and
      mechanism of action, rationale, indications, technique, clinical effectiveness,
      and controversial aspects.

PMID- 16902667
TI  - Innervation of the anterior spinal canal: an update.
AB  - Understanding the innervation of the lumbar spine can be a daunting task. Until
      recently, only macroscopic visualization and crude histological techniques were
      available to document the presence of nerve fibers in the anterior spinal canal.
      Using newer immunohistochemical techniques, studies have been able to more
      thoroughly investigate the innervation of the anterior spinal canal. The presence
      of sensory nerve fibers has been definitively identified in all anterior spinal
      structures. These sensory fibers enable any of the spinal structures the
      capability of being a pain generator. These sensory nerve fibers tend to form
      dense interwoven plexuses on the posterior longitudinal ligament and ventral
      surface of the dura mater. The plexuses allow for anastamoses to take place
      between nerve fibers from multiple segmental levels. This polysegmental formation
      causes the expression of low back pain to be diffuse, rather than focal. It is
      these diffuse pain symptoms that create great difficulty in diagnosing and
      treating spinal canal structures.

PMID- 16902668
TI  - Current applications of electrotherapeutics in collagen healing.
AB  - Electrical current flow appears to be integral to the healing of collagen
      containing tissue, i.e., bone, cartilage, ligaments, tendons and skin.
      Accordingly, it is reasonable to hypothesize that externally applied electrical
      fields should be able to enhance healing, especially in conditions that have
      resisted more standard treatments. Nevertheless, applications of
      electrotherapeutics is challenging because the precise mechanism of action is
      unknown and, accordingly, there is an almost unlimited combination of stimulation
      parameters (e.g., type of waveform, voltage, current, phase, frequency, etc.)
      that can be applied to a treatment site. Presently, of the three major types of
      electrical stimulation, i.e., direct, and capacitive and inductive coupling,
      there is a growing trend toward utilization of the latter because of its efficacy
      and greater margin of safety. Although the mechanisms of action for enhanced
      healing of all three types remain elusive there is increasing evidence that
      electrical stimulation exerts its influence via effects at the cellular and/or
      molecular levels within the tissue. Utilization of electrotherapeutics has been
      most prevalent in bony injuries resistant to healing, but applications to severe
      lesions of skin and ligaments, and even to degenerative joint disease seems
      promising as cartilage has been shown to be more responsive than bone to applied
      electrical energy. We conclude that there is a clear trend toward greater
      orthopedic utilization of inductive stimulation and that, despite the lack of
      definitive guidelines relating specific parameters with specific conditions,
      electrotherapeutics appears to be a safe and often effective treatment for
      collagen containing tissues in many cases in which more standard therapies have
      failed.

PMID- 16902669
TI  - Role of neuraxial steroids in interventional pain management.
AB  - The clinical introduction of cortisone in 1949 revolutionized medical care of
      patients with a host of diseases. Soon after that, the first use of steroids in
      epidural injections was described in 1952 and 1953. A variety of corticosteroid
      agents (hydrocortisone, methylprednisolone, triamcinolone, betamethasone) have
      been applied neuraxially to treat spinal pain and other types of painful
      conditions. The utilization of neuraxial steroids had its empirical beginning in
      the 1950s and 60's. When steroid administration seemingly was effective for
      management of low back pain and sciatica, the concept was adapted for other types
      of neural blockade, including facet joint injections. It is postulated that
      corticosteroids reduce inflammation by inhibiting either the synthesis or release
      of a number of pro-inflammatory substances and by causing a reversible local
      anesthetic effect. Multiple complications of corticosteroid administration are
      two-fold: those resulting from withdrawal of steroids and those resulting from
      continued use of large doses. These include neural toxicity, separation of
      pituitary-adrenal axis, weight gain, osteoporosis, as well as many other
      complications. However, a review of the literature on epidural steroids or other
      types of neuraxial blockade mentions very few complications that can be directly
      attributed either to the chemistry or the pharmacology of the steroids, except
      for reports of adrenal suppression. This review describes various aspects of
      neuraxial steroids including historical concepts, mechanism of action,
      pharmacological aspects, side effects, complications and their role in treatment.

PMID- 16902670
TI  - Do number of pain conditions influence emotional status?
AB  - This study was designed to evaluate psychological status of 150 individuals; 50
      without chronic pain and without psychotherapeutic drug therapy, Group I or
      control group; 50 patients with chronic pain, Group II, chronic pain group with
      involvement of one region; and 50 chronic pain patients with involvement of two
      or more regions, Group III. All the participants were tested utilizing Millon
      Clinical Multiaxial Inventory -III (MCMI-III). Results were analyzed and compared
      for various clinical personality patterns including personality traits and
      personality disorders; severe personality pathology for schizotypal, borderline
      and paranoid personality pathology; and multiple clinical syndromes including
      generalized anxiety disorder, somatization disorder, major depression, bipolar
      manic disorder and dysthymic disorder, etc. There were no significant differences
      noted in clinical personality patterns or severe personality pathology. In the
      analysis of clinical syndromes, generalized anxiety disorder, somatization
      disorder, and depressive disorders were seen in a progressively greater
      proportion of patients in Groups I to III. In conclusion, this evaluation showed
      that abnormal clinical personality patterns are present in both groups of
      patients. Psychological abnormalities with generalized anxiety disorder,
      somatization disorder, and depression are commonly seen in chronic pain patients.

PMID- 16902671
TI  - Seated transforaminal injection approach in severe lumbar stenosis.
AB  - The use of seated positioning for the performance of a fluoroscopically guided
      transforaminal lumbar epidural injection is presented. An 81 year old gentleman
      presented with a lumbar radiculopathy with radiographs demonstrating foraminal
      stenosis arising in the setting of offending disc pathology, multilevel and
      advanced central canal compromise, and a scoliotic deformity. He was unable to
      tolerate prone positioning secondary to radicular pain. A seated approach allowed
      for the patient to remain comfortable, and a satisfactory epidurogram was
      observed. Comparative images of the L4 transforaminal injection performed in the
      prone and seated position may be consistent with an increased foraminal cross
      sectional area in the seated and forward flexed posture.

PMID- 16902672
TI  - The evolution of informed consent: failures of the current system of human
      protection.
AB  - The reliance of subjects and researchers on the current regulatory scheme for
      human subject protection is misplaced. Investigators often assume that compliance
      with the requirements of the Common Rule, including Institutional Review Board
      approval of their research project, adequately fulfills the spirit of the federal
      regulation and protects them from liability for lack of adequate informed
      consent. Subjects and physicians referring subjects, believe that institutional
      approval of studies assures that they are scientifically valid and ethical.
      Unfortunately the current scheme of human research protection has failed to
      fulfill the spirit of the Nuremberg Code and The Belmont Report. Not only are
      large numbers of studies left out of the current protection scheme but the scheme
      is also flawed on several levels. This leaves researchers at risk for liability
      and subjects may have their right to autonomy violated even while the
      requirements of the current regulatory scheme are satisfied. It is time for a
      wholesale restructuring of human subject protection. If physician researchers
      ignore the deficits of the current system we will lose control and input into the
      formulation of the new scheme.

PMID- 16902673
TI  - Cervicogenic headache.
AB  - Chronic headache is a significant medical and socioeconomic problem resulting in
      severe disability and impairment. The term "cervicogenic headache" was coined by
      Sjaastad in 1983, who also proposed criteria for its diagnosis. Cervicogenic
      headache as described by Sjaastad et al is characterized as recurrent, long
      lasting, severe unilateral headache arising from the neck. Exact pathoanatomic
      and pathophysiologic basis for cervicogenic headache is unclear. Numerous authors
      have proposed various theories ranging from neurophysiologic basis involving
      ascending fibers from the C1 and C2 nerve roots to multiple pain generators in
      pain-sensitive structures involved in head movement. Thus, cervicogenic headache
      should be considered as a descriptive term rather than a final diagnosis. Because
      of the numerous potential pain generators, neither uniform clinical findings, nor
      a pathophysiology has been defined for the entity known as cervicogenic headache.
      Sequential diagnostic injections may elucidate pain generators and differentiate
      it from other types of headaches. This review describes the epidemiological and
      clinical aspects of cervicogenic headache, pathophysiology, diagnostic strategies
      to differentiate it from other common headaches and describes various non
      operative treatment strategies.

PMID- 16902675
TI  - Interventional pain medicine: a specialty in the New Millennium.

PMID- 16902674
TI  - Essentials of documentation in interventional pain medicine.
AB  - Documentation in interventional pain medicine is an important, and, at times,
      most crucial facet of practice. For physicians, documentation has always meant
      providing information or evidence on multiple issues, including evaluation and
      management services, procedural services, billing and coding. With the increasing
      sophistication and complexity of interventional medical practices, the need to
      record specific clinical data has grown in importance. Documentation reflects
      competency, character and caring of the pain management specialists. The Office
      of the Inspector General reported overpayments of $23.3 billion in 1996, $20.3
      billion in 1997, $12.6 billion in 1998, $13.5 billion in 1999, $11.9 billion in
      2000, and $12.1 billion in 2001 in health fraud. Thus, the government has been
      increasing its efforts to prevent fraud and abuse by reducing the error rate for
      Medicare-fee-for-service and by improving documentation. Documentation errors
      have contributed to 70% to 80% of the errors. This review describes various
      elements of documentation, documentation standards and the government's
      perspective on documentation, as well as the process of documentation.

PMID- 16902676
TI  - Evaluation of the relative contributions of various structures in chronic low
      back pain.
AB  - An attempt was made to determine the relative contribution of various structures
      to chronic low back pain, including facet joint(s), disc(s), and sacroiliac
      joint(s) in a prospective evaluation. Precision diagnostic blocks, including disc
      injections, facet joint blocks, and sacroiliac joint injections, are frequently
      used. In contrast, selective nerve root blocks or transforaminal epidural
      injections are used occasionally to evaluate persistent or recurrent low back
      pain in patients without appropriate radiologic or neurophysiologic diagnosis.
      One hundred and twenty patients with a chief complaint of low back pain were
      evaluated with precision diagnostic injections, which included medial branch
      blocks, provocative discography and sacroiliac joint injections. In 40% (95% CL,
      31%, 49%), of the patients, facet joint pain was diagnosed; and in 26% (95% CL,
      18%, 34%) of the patients discogenic pain was diagnosed; and 2% of the patients
      were diagnosed with sacroiliac joint pain.

PMID- 16902677
TI  - Metastatic prostate cancer to the spine and a PSA of 5666: a case report.
AB  - Prostate cancer is the most commonly diagnosed cancer and the second most common
      cause of cancer death among American men. To our knowledge, the highest reported
      prostate specific antigen (PSA) level on initial presentation is 3280 ng/mL. In
      this case report, we discuss a 46-year-old African-American man with back pain of
      1-month's duration. A magnetic resonance imaging study of the lumbar spine
      revealed numerous osseous metastatic lesions, and the PSA level was found to be
      5666 ng/mL. He was treated with oral narcotics and a Duragesic patch to achieve
      analgesia and bicalutamide (Casodex) and leuprolide acetate (Lupron) therapy for
      androgen blockade. Later in his course, he required chemotherapy due to hormone
      refractory prostate cancer. The patient has done well as shown at his latest
      follow-up at 48 months. The objective of this report is to discuss the first
      patient with metastatic prostate cancer to the spine with PSA level greater than
      3,500 ng/mL.

PMID- 16902678
TI  - Caudal epidural injections with sarapin or steroids in chronic low back pain.
AB  - Epidural steroid injections are the most commonly used procedures to manage
      chronic low back pain in interventional pain management settings. Approaches
      available to access the epidural space in the lumbosacral spine include the
      interlaminar, transforaminal, and caudal. The overall effectiveness of epidural
      steroid injections has been highly variable. This study included 65 patients who
      underwent diagnostic facet joint nerve blocks utilizing comparative local
      anesthetic blocks and were shown to be negative for facet joint pain and other
      problems such as sacroiliac joint pain before enrollment into the study. They
      were randomly selected from 105 patients negative for facet joint pain allocated
      into three groups, with Group I consisting of 15 patients comprising a
      convenience control sample treated conservatively; Group II, consisting of 22
      patients treated with caudal epidural with local anesthetic and Sarapin(R); and
      Group III, consisting of 33 patients treated with caudal epidural with a mixture
      of local anesthetic, and betamethasone. The study period lasted for 3 years.
      Results showed that there was significant improvement in patients receiving
      caudal epidural injections, with a decrease in pain associated with improved
      physical, functional and mental status; and decreased narcotic intake combined
      with return to work. The study showed that at 1 month 96% of the patients
      evaluated showed significant improvement, which declined to 56% at 3 months and
      16% at 6 months, with administration of 1 to 3 injections. Cumulative relief with
      1 to 12 injections was noted in 96% of the patients at 1 month, 95% at 3 months,
      85% at 6 months, and 67% at 1 year. The study also showed cost effectiveness of
      this treatment, with a cost of $ 2550 for 1-year improvement of quality of life .
      In conclusion, caudal epidural injections with steroids or Sarapin are an
      effective modality of treatment in managing chronic, persistent low back pain
      that fails to respond to conservative modalities of treatments and is also
      negative for facet joint pain. The treatment is not only effective clinically but
      also is cost effective.

PMID- 16902679
TI  - Osseous stress reaction in a rower diagnosed with positron emission tomography
      (PET): a case report.
AB  - Back injury is one of the most frequently encountered injuries in the collegiate
      rower. The differential diagnosis of back pain in the competitive rower includes
      muscle strain, ligament/tendon injury, stress reaction, stress fracture, and a
      tear in the annulus fibrosis. Endurance sports, such as rowing, have an increased
      frequency of stress injury The diagnosis of stress reaction cannot be made with
      plain radiographs. Many studies have firmly established the efficacy of single
      photon emission computed tomography (SPECT) bone scans and magnetic resonance
      imaging in establishing the diagnosis of a stress reaction We present a case of a
      collegiate rower with mid back pain secondary to a stress reaction of the
      endplates of the costotransverse articulation at the T8 level diagnosed by a
      positive positron emission tomogram study in the setting of a negative SPECT
      scan.

PMID- 16902680
TI  - Radiation exposure to the physician performing fluoroscopically guided caudal
      epidural steroid injections.
AB  - This study was designed to investigate radiation exposure to a physician
      performing fluoroscopically guided caudal epidural steroid injections. The
      prospective study design included 100 consecutive fluoroscopically guided caudal
      epidural steroid injections performed on patients with radiculitis from either
      herniated nucleus pulposus or lumbar spinal stenosis. Radiation exposure was
      monitored with the assistance of a radiological technologist (RT) who allocated
      four dosimetry badges to all physicians performing fluoroscopically guided caudal
      epidural steroid injections on consecutive patients being treated for radicular
      pain. The badges were placed on the ring finger, glasses and both the inside and
      outside of the lead apron worn by the physician. In addition, the RTs also wore a
      marked badge outside his/her lead apron. A control badge was placed 67 inches
      away from the fluoroscopy table, and a second control badge was located in a desk
      over 500 feet away from the procedure, to monitor ambient radiation. The average
      fluoroscopy time per procedure was 12.55 seconds. The average/cumulative exposure
      per procedure was 4.10/410 mREM at the "ring" badge, 2.47/247 mREM at the
      "glasses" badge, 3.98 /398 mREM at the "outside apron" badge and 0.15/15 mREM at
      the "inside" apron; no radiation was detectable at the "outside room" control
      badge. The RT's average exposure during these procedures was below the limit of
      detectability. Radiation exposure to the physician needs to be considered and
      minimized in the performance of spinal interventional procedures. Our study
      demonstrates that radiation exposure to the physician performing fluoroscopically
      guided caudal epidural steroid injections is well within safety limits when
      he/she adheres to proper technique.

PMID- 16902681
TI  - Influence of psychological factors on the ability to diagnose chronic low back
      pain of facet joint origin.
AB  - This study was designed to determine the prevalence of lumbar facet joint pain in
      patients suffering with or without somatization disorder. The study was performed
      using comparative local anesthetic blocks. One hundred consecutive patients with
      chronic low back pain, with or without somatization, were evaluated. The results
      showed that, among patients suffering with chronic low back pain, 44% of the
      patients without somatization and 38% of the patients with somatization were
      positive for facet joint pain. The diagnosis of facet joint pain was not
      influenced by the presence or absence of somatization disorder. The evaluation
      also was extended to depression, generalized anxiety disorder and combinations
      with or without somatization thereof which showed no significant differences in
      the prevalence of facet joint pain. The results of this study demonstrated that
      the facet joint was a source of pain in chronic low back pain patients in 44% of
      the patients without somatization and 38% of the patients with somatization. This
      study also showed that there was no correlation between the presence or absence
      of facet joint pain and the presence or absence of somatization disorder or any
      other psychological condition or combination thereof.

PMID- 16902682
TI  - Prevalence of opioid abuse in interventional pain medicine practice settings: a
      randomized clinical evaluation.
AB  - While drug therapy is one of the most commonly used modalities of treatment in
      managing persistent or chronic pain, controversy continues with regards to the
      appropriate use of controlled substances, specifically opioid analgesics, in
      interventional pain medicine settings. This study included 100 randomly selected
      patients receiving opioids in an interventional pain medicine setting. The
      patient's controlled substance profile was evaluated using multiple means. The
      patients were divided into two groups, with 76 patients in the non-abuse group
      and 24 patients in the abuse group after data collection. There were no
      significant differences noted either in demographic characteristics or
      psychological characteristics, except for a higher prevalence of depression in
      the abuse group. In conclusion, there was significant abuse of opioids in an
      interventional pain medicine setting, with an incidence of 24%, with frequent
      abuse seen in almost half of these patients. Thus, it is important for
      interventional pain physicians to recognize this possibility and also to
      recognize that there is no definite physiologic, psychologic or demographic
      information to suggest abuse, even though depression was more prevalent in abuse
      patients.

PMID- 16902683
TI  - Effectiveness of percutaneous adhesiolysis with hypertonic saline neurolysis in
      refractory spinal stenosis.
AB  - The increasing proportion of elderly patients, coupled with increasing longevity,
      causes the problem of lumbosacral pain secondary to spinal stenosis of the lumbar
      spine to be an important issue. Symptoms of spinal stenosis are caused by
      entrapment and compression of intraspinal vascular and nervous structures; which
      may lead to inactivity, loss of productivity, and potential loss of independence,
      particularly in the elderly. Surgical decompression is considered as the natural
      treatment. However, the results of surgical treatments have been mixed. Results
      of conservative treatment are also not encouraging. While the effectiveness of
      caudal epidural blocks for lumbar canal stenosis was positive, the effectiveness
      of interlaminar epidural steroid injections showed no beneficial effects on
      symptomatology of spinal stenosis. Percutaneous epidural adhesiolysis with
      hypertonic saline neurolysis has been studied in patients with refractory low
      back pain secondary to post lumbar laminectomy syndrome, as well as spinal
      stenosis. The specific role of adhesiolysis and hypertonic saline neurolysis in
      the management of refractory low back and lower extremity pain secondary to
      spinal stenosis has not been studied. This retrospective evaluation included 18
      patients derived from a total sample of 239 patients undergoing adhesiolysis and
      hypertonic saline neurolysis over a period of 3 years. The results showed
      significant improvement with reduction of pain; with improvement of physical
      health, mental health, and functional status. Improvement in psychological status
      was also noted, with decrease in narcotic intake. Epidural adhesiolysis with
      hypertonic saline neurolysis is a safe and probably effective modality of
      treatment in managing symptomatic moderate to severe lumbar spinal canal
      stenosis.

PMID- 16902684
TI  - Beyond the basics: implementing the HIPAA Privacy Standards in real life
      situations.

PMID- 16902685
TI  - Role of correct coding for interventional techniques.
AB  - There has been enormous emphasis on the description and definition of what the
      physician does for and to the patient, with fraud and abuse evolving as an
      important aspect of interventional pain medicine. Compliance with the laws and
      regulations encompassing documentation with coding, billing, and collections, and
      medical records, is crucial in today's interventional pain medicine practices.
      The Health Insurance Portability and Accountability Act of 1996, provided the
      Office of Inspector General and the Federal Bureau of Investigations with broad
      powers and directed them to identify and prosecute health-care fraud and abuse.
      The National Correct Coding Council was created by Centers for Medicare and
      Medicaid Services to help ensure that providers across various jurisdictions
      receive like payments for the same services, use the same codes and provide
      similar documentation for services performed. As a direct outgrowth of the
      National Correct Coding Council's work, the Centers for Medicare and Medicaid
      Services established the National Correct Coding Policy in 1996 and eventually
      implemented the Correct Coding Initiative (CCI) to identify and isolate
      inappropriate coding, unbundling, and other irregularities in coding. Multiple
      versions of National Correct Coding Policies have been released in the form of
      National Correct Coding manuals ranging from version 5.0 to 7.2. This review
      discusses various aspects of correct coding in interventional pain medicine.

PMID- 16902686
TI  - Characteristics of chronic low back pain in patients in an interventional pain
      management setting: a prospective evaluation.
AB  - Chronic low back pain patients are seen in multiple practice settings and managed
      with a multitude of therapeutic interventions. Studies conducted by various
      groups have made some generalizations in the literature describing low back pain
      patients. However, there are no studies evaluating the demographic features of
      patients presenting to therapeutic interventional pain medicine programs. This
      prospective study was undertaken to evaluate and explore various demographic
      features of patients with chronic low back pain presenting to a therapeutic
      interventional pain medicine program. Two hundred patients were studied, with
      evaluation of demographic features of age, mode of onset of pain, work status,
      history of surgery, and pain characteristics. The results showed that, among
      patients presenting to an interventional pain medicine program, 17% are over 65
      years of age: they are predominantly women; two thirds are either overweight or
      obese; the mean duration of pain is 7 years, predominantly involving multiple
      regions, with an average pain intensity of 7.6, significant associated
      psychological conditions; they have undergone multiple interventions, and were
      seen by, on average, six physicians; and the majority of patients were not
      employed, with 31% unemployed and 52% disabled or retired.

PMID- 16902687
TI  - Sacroiliac joint syndrome.
AB  - The sacroiliac joint has long been considered to be a potential source of low
      back and/or buttock pain with or without lower extremity symptoms. Until
      recently, supportive evidence for this disorder has been empirical as it was
      solely derived from information garnered from patients who obtained successful
      treatment for a constellation of signs, symptoms and examination findings
      believed to be indicative of sacroiliac joint syndrome. Due to this fallacious
      reasoning, successful treatment denotes a correct diagnosis; many of the concepts
      espoused during the past few decades have been predicated upon spurious data.
      With the advent of and systematic utilization of fluoroscopically guided
      diagnostic sacroiliac joint blockade specific epidemiologic, symptomatic,
      examination, diagnostic, and outcome data have been derived. This review
      describes current concepts and provides information that expounds and, in some
      instances, supplants prior held notions about this disorder.

PMID- 16902688
TI  - Role of one day epidural adhesiolysis in management of chronic low back pain: a
      randomized clinical trial.
AB  - Epidural fibrosis is seen as a common phenomenon among postlumbar laminectomy
      syndrome patients, contributing to approximately 60% of symptom recurrence.
      Percutaneous epidural lysis of adhesions has been described as a modality to
      effectively manage chronic low back pain secondary to epidural fibrosis. Forty
      five patients were randomly assigned, with fifteen patients in the control group,
      or Group I, who were treated with conservative modalities of treatments,
      including medication, physical therapy, and an exercise program; and, thirty
      patients in Group II, who were treated with percutaneous epidural adhesiolysis
      and hypertonic saline neurolysis. The patients were evaluated over a period of 1
      1/2 years to 3 years. Results showed that cumulative relief, defined as relief
      greater than 50% with one to three injections, in the treatment group was 97% at
      3 months, 93% at 6 months, and 47% at 1 year. The study also showed that overall
      health status improved significantly in the treatment group in all parameters
      with average pain, physical health, mental health, functional status,
      psychological status and narcotic intake. Analysis also showed that this is a
      cost-effective treatment, with cost for 1-year improvement of quality of life at
      $2693. In conclusion, epidural adhesiolysis with hypertonic saline neurolysis
      performed on a 1-day basis is an effective modality of treatment in managing
      chronic low back pain in patients who failed to respond to fluoroscopically
      directed epidural steroid injections and also were demonstrated not to have facet
      joint mediated pain.

PMID- 16902689
TI  - Outcomes of therapeutic selective nerve root blocks for whiplash induced cervical
      radicular pain.
AB  - This study was designed to investigate the clinical efficacy of fluoroscopically
      guided therapeutic cervical selective nerve root blocks (SNRBs) in patients with
      whiplash induced cervical radicular pain. Study design was restrospective with
      independent clinical review. Twenty two patients were included. Each patient met
      specific physical examination criteria and failed to improve clinically after at
      least four weeks of physical therapy and the use of oral analgesics. Each patient
      demonstrated a positive response to a fluoroscopically guided diagnostic cervical
      SNRB. Patients were excluded for radiographic evidence of a focal disc protrusion
      or foraminal stenosis at the symptomatic level. Therapeutic cervical SNRBs were
      administered in conjunction with physical therapy. Data collection and analysis
      were performed by an independent clinical reviewer. Outcome measures included VAS
      pain scores, work status, medication usage, and Oswestry disability scores.
      Results showed the patients' symptom duration prior to diagnostic injection
      averaged 6 months. An average of 2.1 therapeutic injections was administered.
      Follow up data collection transpired at an average of 33.3 weeks following the
      final therapeutic injection. Good or excellent results were observed in 14% of
      patients. In higher functioning individuals a significantly greater (F=.0427)
      improvement in pain of 48.9% was observed. In these initial findings suggest that
      fluoroscopically guided therapeutic SNRBs, except possibly for higher functioning
      individuals, are not effective in the treatment of whiplash induced cervical
      radicular pain.

PMID- 16902690
TI  - Contribution of facet joints to chronic low back pain in postlumbar laminectomy
      syndrome: a controlled comparative prevalence evaluation.
AB  - Postlumbar laminectomy syndrome, or pain following operative procedures of the
      lumbar spine, is increasingly a common entity in modern medicine. Multiple causes
      proposed for recurrence of pain after lumbar laminectomy are: epidural fibrosis,
      recurrent disc herniation, instability, and facet joints. Even though the
      prevalence of persistent low back pain secondary to the involvement of
      lumbosacral facet joints has been described in controlled studies from 15% to
      45%, the prevalence of facet joint mediated pain in postlumbar laminectomy
      syndrome has not been studied. This prospective, randomized, controlled
      comparative evaluation was performed to determine the prevalence of facet joint
      mediated pain in persistent low back pain in postlumbar laminectomy patients with
      a comparative non-surgical group. One hundred patients with fifty patients in
      each group were randomly assigned with group I consisting of fifty patients
      without history of previous surgery and group II consisting of fifty patients
      with history of previous surgery. Results showed that the prevalence of facet
      joint mediated pain in non-surgical patients was 44% compared to 32% in post
      surgical patients determined by comparative controlled local anesthetic blocks
      utilizing lidocaine and bupivacaine. This study also showed a false positive rate
      of 36% in non-surgical group and 24% in post-surgical group. In conclusion, this
      study shows that facet joint mediated symptomatology in chronic low back pain is
      prevalent, both in non-surgical as well as post-surgical patients even though
      prevalence was somewhat higher in the non-surgical group compared to post
      surgical group.

PMID- 16902691
TI  - Growing pains: can any willing provider laws overcome the challenges of the
      teenage years?
AB  - Any willing provider laws were first enacted in the late 1980's as a way to
      combat the exclusion of providers from insurer and Health Maintenance
      Organization (HMO) network panels. Generally, the laws provided that insurers and
      managed care organizations had to admit to their provider panels any provider who
      was willing to accept the entity's terms and conditions for participation. These
      laws face two significant challenges today: how to overcome Employee Retirement
      Income Security Act (ERISA) preemption and the fact that the legislatures either
      failed to put limits on the terms and conditions that could be imposed or did not
      define what reasonable terms and conditions were. This article gives a basic
      overview of any willing provider laws, the ERISA statutory and case law that
      affects them, and the current problem of what terms and conditions imposed upon
      providers can be considered reasonable. It also summarizes many of the current
      any willing provider laws and notes which laws among those listed have been held
      by courts to be preempted by ERISA. Efforts have been taken to make this article
      current and accurate; however, they should not be construed as legal advice or an
      opinion on specific situations. Because of the rapid pace with which these laws
      and the cases affecting them change, you should consult an attorney concerning
      the existence and validity of any willing provider and similar laws in your
      state.

PMID- 16902692
TI  - Needlestick safety and prevention act.
AB  - The Needlestick Safety and Prevention Act to revise the Occupational Safety and
      Health Administration's (OSHA) standard regulating occupational exposure to
      bloodborne pathogens, including the human immunodeficiency virus, the hepatitis B
      virus, and the hepatitis C virus, was signed into law on November 6, 2000. OSHA
      published in the Federal Register its regulations reflecting the Act and its
      requirments. The effective date of the regulations is April 18, 2001. The
      Needlestick Safety and Prevention Act seeks to further reduce health care
      workers' exposure to bloodborne pathogens by imposing additional requirements
      upon employers, such as hospitals and ASCs, concerning their sharps procedures.
      Consistent with the Act, OSHA's regulations (1) modify the definition of
      "engineering controls" and adds definitions for the terms "sharps with engineered
      sharps injury protection" and "needleless systems," (2) requires employers to
      consider and implement new technologies when they update their "exposure control
      plan," (3) requires employers to solicit employee input with respect to
      appropriate engineering controls, and (4) requires employers to maintain a sharps
      injury log. Practical questions about implementing the new requirements are a
      source of major concern. The House Committee on Education and the Workforce
      stated in legislative history to the Act that the statute was not meant to
      disturb the underlying flexible, performance-oriented nature of the Initial
      Standard.

PMID- 16902693
TI  - Impact of Stark II Rules on interventional pain practices.
AB  - The original Stark Law, commonly referred to as "Stark I," was enacted in 1989.
      Stark I prohibited a physician from ordering a clinical laboratory test or
      service from an entity with which the physician, or an immediate family member,
      had a financial relationship if the test or service was reimbursable by Medicare,
      unless an exception to the law applies. The Stark Law was amended in 1993. The
      amendments are commonly referred to as "Stark II." Stark II extended the referral
      prohibition to services reimbursable under Medicaid and greatly expanded the list
      of items and services covered by the law i.e., "designated health services." HCFA
      published phase I of the Final Stark Rules on January 4, 2001. These rules dealt
      with referral definition issues, volume or value of referrals, in-office
      ancillary services exception, group practice definition, and definitions of
      designated health services. This article describes phase I of Stark II Final
      Rules, and its impact on interventional pain medicine practices.

PMID- 16902696
TI  - In pursuit of evidence based integrated care.

PMID- 16902694
TI  - Integrated care for the elderly: the background and effects of the reform of
      Swedish care of the elderly.

PMID- 16902697
TI  - Primary health care in the Czech Republic: brief history and current issues.
AB  - The objective of this paper is to describe the recent history, current situation
      and perspectives for further development of the integrated system of primary care
      in the Czech Republic. The role of primary care in the whole health care system
      is discussed and new initiatives aimed at strengthening and integrating primary
      care are outlined. Changes brought about by the recent reform processes are
      generally seen as favourable, however, a lack of integration of health services
      under the current system is causing various kinds of problems. A new strategy for
      development of primary care in the Czech Republic encourages integration of care
      and defines primary care as co-ordinated and complex care provided at the level
      of the first contact of an individual with the health care system.

PMID- 16902698
TI  - Interview with Dr. Hunter: about the report "On the state of young people's
      health in the European Union" and integrated care in Europe.

PMID- 16902699
TI  - Fully integrated care for frail elderly: two American models.
AB  - PURPOSE: Integrated care for the frail elderly and other populations with
      complex, chronic, disabling conditions has taken centre stage among policymakers,
      planners and providers in the United States and other countries. There is a
      growing belief that integrated care strategies offer the potential to improve
      service co-ordination, quality outcomes, and efficiency. Therefore, it is
      critical to have a conceptual understanding of the meaning of integrated care and
      its various organisational models, as well as practical examples of how such
      models work. This article examines so-called "fully integrated" models of care in
      detail, concentrating on two major, well-established American programs, the
      social health maintenance organisation and the program of all-inclusive care for
      the elderly. THEORY: A major challenge to understanding the performance and
      outcomes of fully integrated care and other organisational models is the lack of
      a meaningful, analytical paradigm. This article builds upon the work of Walter
      Leutz, to develop a framework by which new and existing programs can be analysed.
      This framework is then applied to the two American models that are the focus of
      this article. METHODS: Existing data about integrated care in general, and the
      two model programs in particular, were collected and analysed from reports
      published by governmental and non-governmental organisations, and journal
      articles retrieved from Medline, HealthStar and other sources. RESULTS AND
      CONCLUSIONS: This analysis strongly suggests that fully integrated models of
      care, such as the social health maintenance organisation and program of all
      inclusive care for the elderly, are not only feasible, but offer significant
      potential to improve the delivery of health and social care for frail elderly
      patients. In addition, the authors identify the factors that are the most
      critical to the success of fully integrated care, and offer lessons for their
      development and implementation. Finally, issues are raised concerning the
      transferability of this complex model to other countries, as well as the vital
      importance of evidence-based evaluation research in furthering the evolution of
      integrated care.

PMID- 16902700
TI  - Integrated and fragmented care observed from two case studies.

PMID- 16902701
TI  - Can shared care deliver better outcomes for patients undergoing total hip
      replacement? A prospective assessment of patient outcomes and associated service
      use.
AB  - OBJECTIVES: To assess whether shared care for patients undergoing total hip
      replacement delivers better outcomes compared to care as usual. DESIGN:
      Prospective, observational cohort study. SETTING: Two regions in The Netherlands
      where different organisational health care models have been implemented: a shared
      care setting (experimental group) and a care as usual setting (control group).
      PATIENTS: One hundred and fifteen patients undergoing total hip replacement: 56
      in the experimental group and 59 in the control group. MAIN MEASURES: Functional
      health status according to the sickness impact profile, hip function, patient
      satisfaction and use of health care services. RESULTS: Two weeks before hip
      replacement both groups were comparable concerning patient characteristics, hip
      function and health status. The mean improvement of the total sickness impact
      profile score between two weeks before hip replacement and six months after was 
      1.92 in the shared care group, compared to -5.11 in care as usual group, a
      difference in favour of the control group (p=0.02). The mean length of hospital
      stay was comparable in both settings: 12.8 days in the shared care group and 13.2
      days in the care as usual group. After hip replacement, compared to care as
      usual, patients in the shared care group received more homecare, with a higher
      frequency, and for a longer period of time. No differences in patient
      satisfaction between the two groups were found. CONCLUSIONS: Six months after hip
      replacement, the health status of patients in the care as usual group, using
      significantly less home care, was better than the status of patients in the
      shared care group. DISCUSSION: The utilisation of home care after hip replacement
      should be critically appraised in view of the need to stimulate patients'
      independence.

PMID- 16902702
TI  - The frustrations of families: Henry Lynch, heredity, and cancer control, 1962
      1975.

PMID- 16902703
TI  - Design for control: surgery, science, and space at the Royal Victoria Hospital,
      Montreal, 1893-1956.

PMID- 16902704
TI  - Health, sickness and medical services in Spain's Armed Forces c.1665-1700.

PMID- 16902705
TI  - Passive trust or active application: changes in the management of difficult
      childbirth and the Edinburgh Royal Maternity Hospital, 1850-1890.

PMID- 16902706
TI  - Medical and chemical expertise in English trials for criminal poisoning, 1750
      1914.

PMID- 16902707
TI  - A Babylonian perspective on Greek medicine.

PMID- 16902709
TI  - Looking at long molecules in solution: what happens when they are subjected to
      Couette flow?
AB  - Knowing the structure of a molecule is one of the keys to deducing its function
      in a biological system. However, many biomacromolecules are not amenable to
      structural characterisation by the powerful techniques often used namely NMR and
      X-ray diffraction because they are too large, or too flexible or simply refuse to
      crystallize. Long molecules such as DNA and fibrous proteins are two such classes
      of molecule. In this article the extent to which flow linear dichroism (LD) can
      be used to characterise the structure and function of such molecules is reviewed.
      Consideration is given to the issues of fluid dynamics and light scattering by
      such large molecules. A range of applications of LD are reviewed including (i)
      fibrous proteins with particular attention being given to actin; (ii) a far from
      comprehensive discussion of the use of LD for DNA and DNA-ligand systems; (iii)
      LD for the kinetics of restriction digestion of circular supercoiled DNA; and
      (iv) carbon nanotubes to illustrate that LD can be used on any long molecules
      with accessible absorption transitions.

PMID- 16902711
TI  - Evidence for laser-induced formation of solvated electrons in room temperature
      ionic liquids.
AB  - The photolytic generation of solvated electrons was observed for the first time
      in two room temperature ionic liquids (RTILs), trihexyltetradecylphosphonium
      bis(trifluoromethylsulfonyl)imide (IL) and 1-butyl-1-methyl-pyrrolidinium
      bis(trifluoromethylsulfonyl)imide (IL). A 70 fs UV-pulse was used to excite the
      RTILs, while the transient response was monitored in the visible and near
      infrared spectral regions. Immediately after excitation, a pulse duration limited
      rise of the induced absorption indicated the formation of solvated electrons
      suggesting the existence of pre-formed traps in RTILs. A broad transient
      absorption spectrum with a full width at half maximum of about 0.9 eV, typical
      for solvated electrons, was reconstructed from the transient profiles. Wavelength
      independent relaxation dynamics at longer delay times suggest a lifetime of
      solvated electrons in the ns regime in agreement with results from pulse
      radiolysis studies. Adding 1,1-dimethylpyrrolidinium iodide to IL led to an
      increase of the UV absorbance and consequently, to an increase of the yield of
      solvated electrons. Furthermore, this solute is an efficient electron scavenger
      causing the transients to decay within about 40 ps.

PMID- 16902710
TI  - Advances in methods and algorithms in a modern quantum chemistry program package.
AB  - Advances in theory and algorithms for electronic structure calculations must be
      incorporated into program packages to enable them to become routinely used by the
      broader chemical community. This work reviews advances made over the past five
      years or so that constitute the major improvements contained in a new release of
      the Q-Chem quantum chemistry package, together with illustrative timings and
      applications. Specific developments discussed include fast methods for density
      functional theory calculations, linear scaling evaluation of energies, NMR
      chemical shifts and electric properties, fast auxiliary basis function methods
      for correlated energies and gradients, equation-of-motion coupled cluster methods
      for ground and excited states, geminal wavefunctions, embedding methods and
      techniques for exploring potential energy surfaces.

PMID- 16902713
TI  - Experimental and theoretical study of the reaction of OH radical with sabinene.
AB  - The gas phase sabinene + OH reaction is studied both experimentally and
      theoretically. Product yields from the reaction of sabinene with OH radicals have
      been measured in the absence of NOx in the UCC chamber (Cork, Ireland) and in the
      presence of NOx in the LISA chamber. Three primary carbonyl compounds were
      observed and quantified: acetone in [(24 +/- 6)%], formaldehyde in [(25 +/- 6)%]
      and sabinaketone in [(20 +/- 6)%]. The simultaneous quantification of these
      compounds is one of the major results of this work. The mechanism of product
      formation for this reaction has been studied using the quantum chemical DFT-B3LYP
      (6-31G(d,p) method. According to these calculations, the H-atom abstraction
      channel from sabinene by OH in the initial oxidation step may be taken into
      account to explain the acetone production. Sabinaketone and formaldehyde are
      mainly products of the addition channels of OH on the -C=CH2 double bond of
      sabinene. This is the first theoretical work on the title reaction.

PMID- 16902712
TI  - Evaluation of models for the low temperature combustion of alkanes through
      interpretation of pressure-temperature ignition diagrams.
AB  - The purpose of this paper is to show the application of global uncertainty
      analysis to comprehensive and reduced kinetic models as a tool to identify
      important thermochemical and reaction rate parameters as determinants of the
      conditions leading to autoignition. Propane oxidation is taken as the test case.
      The simulation of experimental investigations of the cool flames and two-stage
      ignitions, via the pressure-temperature ignition diagram, show that existing
      kinetic models for the low temperature combustion of propane at sub-atmospheric
      pressures reflect a greater reactivity than seems to be appropriate. That is, the
      models lead to a prediction of two-stage ignition at pressures somewhat lower and
      with ignition delays shorter than is found experimentally. The inconsistency
      between experiment and numerical simulation seems not to be an inherent problem
      of the qualitative structure of the models, but may derive from uncertainties in
      the parameters within the mechanism. By use of "brute force", Morris-one-at-a
      time and Monte-Carlo simulations, we show that uncertainties in only a small
      number of parameters, and falling well within the errors that may reasonably be
      assigned, can shift the response appropriately. Moreover, it appears that in the
      low temperature combustion regime, thermochemistry is at least as, if not more,
      important than the reaction rates, yet usually receives less attention within
      sensitivity studies. In the present case, the main factors controlling the
      temperature reached in the first stage of two-stage ignition and the time to
      ignition appear to be connected with the thermochemistry of three specific
      hydroperoxyalkyl radicals and their derivatives. Other factors, such as heat and
      mass transport are also addressed, and their effects are mitigated to some extent
      by evaluation of initial and revised models against experimental data for
      ignition delay obtained under microgravity. The results highlight more general
      issues that pertain to the numerical simulation of the combustion of higher
      hydrocarbons and contribute to the development of the protocol necessary for
      testing kinetic models before they are ready for use in a predictive capacity.

PMID- 16902714
TI  - Interface identification by non-local autoionization transitions.
AB  - We use an autoionization process that involves ultrafast energy transfer to
      neighbouring sites to characterize the formation of NeAr van der Waals bonds in
      clusters formed by a coexpansion of both gases. This autoionization process, the
      so-called interatomic or intermolecular coulombic decay (ICD), is ubiquitous in
      weakly bonded systems. The energy of the electron being emitted in the ICD
      process is shown to be characteristic of the two neighbouring entities and is
      therefore suggested as a new means for structural investigation, such as
      interface identification, of weakly bonded complexes.

PMID- 16902715
TI  - Enthalpy and interfacial free energy changes of water capillary condensed in
      mesoporous silica, MCM-41 and SBA-15.
AB  - The effect of confinement on the solid-liquid phase transitions of water was
      studied by using DSC and FT-IR measurements. Enthalpy changes upon melting of
      frozen water in MCM-41 and SBA-15 were determined as a function of pore size and
      found to decrease with decreasing pore size. The melting point also decreased
      almost monotonically with a decrease in pore size. Analysis of the Gibbs-Thomson
      relation on the basis of the thermodynamic data showed that there were two stages
      of interfacial free energy change after the constant region, i.e., below a pore
      size of 6.0 nm: a gradual decrease down to 3.4 nm and another decrease after a
      small jump upward. This fact demonstrates that the simple Gibbs-Thomson relation,
      i.e., a linear relation between the melting point change and the inverse pore
      size, is limited to the range not far from the melting point of bulk water. FT-IR
      measurements suggest that the decrease in enthalpy change and interfacial free
      energy change with decreasing pore size reflect the similarity of the structures
      of both liquid and solid phases of water in smaller pores at lower temperatures.

PMID- 16902716
TI  - ATR-FTIR measurements and quantum chemical calculations concerning the adsorption
      and photoreaction of oxalic acid on TiO2.
AB  - The adsorption and photoreaction of oxalic acid on the surface of anatase and
      rutile TiO2 nanoparticles have been studied using a combined experimental and
      theoretical approach. In the dark, the experimental adsorption reaches an
      equilibrium state that can be described as a mixture of adsorbed water and oxalic
      acid molecules, with the latter forming two different surface complexes on
      anatase and one on rutile particles. When the system is subsequently illuminated
      with UV(A) light, the surface becomes enriched with absorbed oxalic acid, which
      replaces photo-desorbed water molecules, and one of the adsorbed oxalic acid
      structures on anatase is favoured over the other.

PMID- 16902717
TI  - Analysis of in situ EXAFS data of supported metal catalysts using the third and
      fourth cumulant.
AB  - X-Ray absorption spectra of supported Pt catalysts with various Pt cluster sizes
      were collected between 77 and 673 K, in inert and hydrogen atmospheres. When
      analyzing these spectra with the standard EXAFS equation, a Pt-Pt bond
      contraction and a large increase in the inner potential correction were observed
      with increasing temperature. These errors are up to 0.08 A and 10 eV for clusters
      of 1 nm diameter. They were corrected by including the third and fourth cumulants
      as fit parameters. Fit guidelines were developed to analyze EXAFS data of
      supported metal catalysts collected at elevated temperatures, allowing for
      asymmetry and broadening or sharpening of the pair distribution function. These
      comprise fixing fit parameters, using different k-weightings and identifying
      trends in a series of experiments. By fitting the EXAFS spectra using these
      guidelines, it was determined that in small Pt clusters the Pt-Pt bond is 0.10 A
      shorter than in bulk Pt. These contracted bonds relax to distances near that of
      bulk Pt upon hydrogen chemisorption.

PMID- 16902718
TI  - Medicalising the treatment of opioid dependence.

PMID- 16902719
TI  - Socio-demographic profile and help-seeking behaviour of buprenorphine abusers in
      Singapore.
AB  - INTRODUCTION: The US Food and Drug Administration (FDA) approved buprenorphine or
      Subutex for the treatment of opiate dependence in October 2002. Buprenorphine is
      a partial agonist of the mu-opioid receptor; although initial animal research
      suggested a low abuse potential for buprenorphine, it was subsequently shown to
      have an abuse potential similar to that of morphine or hydromorphone. The
      objectives of this study were to establish the sociodemographic profile and help
      seeking behaviour of buprenorphine abusers attending the deaddiction treatment
      clinics of the Community Addictions Management Programme. MATERIALS AND METHODS:
      One hundred and twenty subjects, all buprenorphine abusers fulfilling the
      diagnostic criteria for opiate dependence, who consented to the study, completed
      an interviewer-administered questionnaire. RESULTS: The mean age of those
      participating in the study was 39.2 [standard deviation (SD) 8.0] years. The
      majority of the participants were male (90%), 52.5% were currently employed and
      98% had at least primary education. A family history of drug abuse was reported
      by 27% of the subjects. Illicit drug abuse occurred at an early age with mean age
      of onset of illicit drug abuse being 16.9 (SD 4.8) years with gateway drugs like
      marijuana and glue. CONCLUSIONS: It is vital for our medical profession to be
      aware of the trend in the local population to move from the abuse of illicit
      substances, to the abuse of prescriptive medications. It makes it necessary to
      increase the understanding of addictions both amongst our practising medical
      fraternity, and amongst those training to enter the profession. At the hospital
      level, it necessitates a higher level of vigilance among our emergency room
      physicians and those treating infectious diseases.

PMID- 16902720
TI  - Reducing polypharmacy through the introduction of a treatment algorithm: use of a
      treatment algorithm on the impact on polypharmacy.
AB  - INTRODUCTION: Polypharmacy is very common in the psychiatric setting despite the
      lack of evidence to justify its use. The objective of this study was to review
      the prescription patterns in a tertiary mental health institute in Asia and
      evaluate the impact of a treatment algorithm for patients with first-episode
      psychosis (FEP) on the use of polypharmacy. MATERIALS AND METHODS: A treatment
      algorithm was implemented for patients accepted into an Early Psychosis
      Intervention Programme (EPIP) and the prescription patterns of these patients
      were compared with a comparator group (pre-EPIP) before the use of the algorithm.
      The prescribing pattern was established at 2 points: at baseline after the
      diagnosis was made, and 3 months later. RESULTS: There were 68 subjects in the
      comparator group and 483 EPIP patients; the latter were on the average younger.
      None in the comparator group was diagnosed to have an affective psychosis. There
      was a significant reduction in the rate of antipsychotic polypharmacy, prolonged
      use of benzodiazepines and anticholinergic medication in EPIP patients. This
      group also had an increase in the use of second-generation antipsychotics and
      received lower doses of antipsychotics. CONCLUSION: The implementation of a
      treatment algorithm coupled with audit has changed the trend towards polypharmacy
      among patients with FEP.

PMID- 16902721
TI  - Utility and validity of the self-administered SF-36: findings from an older
      population.
AB  - INTRODUCTION: The objectives of this study were to assess the utility and
      validity of the self-administered SF-36 and the effect of visual or cognitive
      impairment on these measures in an older population. MATERIALS AND METHODS:
      Attempt rates, completion rates and internal consistency (Cronbach alpha) were
      compared within the second cross-sectional, population-based Blue Mountains Eye
      Study (n = 3509, mean age 66.7 years, 57% women). RESULTS: The SF-36 was
      attempted by 3162 (90.1%) participants, of which 2470 (78.1%) completed all items
      and 2873 (90.9%) completed sufficient items for calculation of all dimensions. In
      a multivariate model adjusting for age, sex, and presenting visual and cognitive
      impairments, women (P = 0.011) and participants with visual or cognitive
      impairments (P < 0.0001) were less likely to attempt the questionnaire.
      Completion rates were significantly lower with increasing age (P < 0.0001), in
      men (P < or = 0.0005) and in those with cognitive impairment (P < 0.0001). A high
      level of internal consistency (Cronbach alpha > 0.85 for all dimensions) and
      construct validity was demonstrated, the latter distinguishing between those with
      and without medical conditions, disabilities or recent hospital admissions (P <
      0.01). As the prevalence of visual or cognitive impairment was relatively low in
      this population, we found no apparent effect of these impairments on the validity
      of SF-36. CONCLUSIONS: Attempt and completion rates, but not internal consistency
      and construct validity, of the SF-36 were influenced by age, gender, and
      presenting visual and cognitive impairments. The overall high attempt and
      completion rates, internal consistency and construct validity suggest that the
      self-administered SF-36 is a suitable healthrelated quality of life (HRQOL)
      measure in similar older community-living populations.

PMID- 16902722
TI  - Plasma and urine amino acid profiles in a healthy adult population of Singapore.
AB  - INTRODUCTION: The analysis of amino acids in plasma and urine was introduced in
      Singapore when a laboratory for the investigation of inherited metabolic
      disorders was established by the Ministry of Health. Reference ranges are
      required for interpreting test results and making diagnoses. Initially, reference
      ranges established for Caucasians were used as there were no local data and we
      were unable to find data obtained by the same analytical method for Asian
      populations. This was not considered an ideal and long-term solution, as
      Singaporeans may have amino acid concentrations quite different from those of
      Caucasians due to genetic factors, dietary difference, environment, and other
      influences. This study was therefore undertaken when a number of healthy
      laboratory personnel volunteered to provide specimens for the study. MATERIALS
      AND METHODS: Sixty healthy male and female laboratory workers not on any form of
      medication were recruited. They consisted of 24 males (range, 23 to 58 years) and
      36 females (range, 20 to 60 years), with a mean age of 38.7 years. Non-fasting
      random blood and urine specimens were collected on ice. Removal of protein and
      peptides from heparinised plasma and urine was achieved by ultrafiltration
      through protein-exclusion membrane. Amino acid analysis on the ultrafiltrate was
      performed by a dedicated Beckman 6300 Amino Acid Analyzer using a cation exchange
      resin column and post-column colour reaction with ninhydrin reagent. Urine
      creatinine was measured by a Beckman LX 20 PRO Analyzer. Results for urine amino
      acids were expressed as micromol/mmol of creatinine. RESULTS: Reference ranges
      for 32 amino acids in blood plasma and 36 amino acids in urine were calculated by
      a non-parametric method using the SPSS statistical calculation software. The
      ranges cover 95% of the population and the low and high limits of each reference
      range represent the 2.5th percentile and 97.5th percentile of the frequency
      distribution respectively. CONCLUSIONS: We observed differences in the reference
      ranges of several plasma and urine amino acids between Singaporean and Caucasian
      populations. Moreover, the list of urine amino acids for Caucasian population is
      incomplete. We have therefore discontinued the use of reference values
      established for Caucasians and adopted the results of this study for our patient
      diagnostic work.

PMID- 16902723
TI  - A novel locus for X-linked retinitis pigmentosa.
AB  - INTRODUCTION: Retinitis pigmentosa (RP) is the most prevalent group of inherited
      retinopathies and demonstrates considerable clinical and genetic heterogeneity,
      with wide variations in disease severity, progression, and gene involvement. We
      studied a large family with RP to determine the pattern of inheritance and to
      identify the disease-causing gene/locus. MATERIALS AND METHODS: Ophthalmic
      examination was performed on 35 family members to identify affected individuals
      and carriers and to characterise the disease phenotype. Genetic linkage analysis
      was performed using short tandem repeat (STR) polymorphic markers encompassing
      the known loci for Xlinked RP (xlRP) including RP2, RP3, RP6, RP23, and RP24.
      Mutation screening was performed by direct sequencing of PCR-amplified genomic
      DNA of the RP2 and RPGR genes of the affected individuals. RESULTS: A highly
      penetrant, X-linked form of RP was observed in this family. Age of onset was from
      5 to 8 years and visual acuity ranged from 20/25 in children to light perception
      in older adults. Linkage analysis and direct sequencing showed that no known
      loci/genes were associated with the phenotype in this kindred. CONCLUSION: A
      novel disease gene locus/loci is responsible for the xlRP phenotype in this
      family.

PMID- 16902724
TI  - Community-associated methicillin-resistant Staphylococcus aureus: overview and
      local situation.
AB  - INTRODUCTION: Community-associated methicillin-resistant Staphylococcus aureus
      (CA-MRSA) has emerged worldwide. In contrast to healthcare-associated MRSA (HA
      MRSA), CA-MRSA isolates are usually susceptible to multiple non-beta-lactam
      antibiotics and cause a distinct spectrum of infections in epidemiologically
      disparate populations - in particular, cutaneous abscesses, necrotising fasciitis
      and necrotising pneumonia. They arise from a broader genetic background, and
      possess differing virulence genes. We aim to describe the distribution of
      different molecular subtypes of CA-MRSA among various regions and discuss briefly
      the implications of CA-MRSA from a local perspective. METHODS: Literature review
      of articles on CA-MRSA, focusing mainly on reports where the genetic background
      of isolates had been analysed using multi-locus sequence typing (MLST). Singapore
      data were obtained from the local CA-MRSA database. RESULTS: MLST analysis
      demonstrated the presence of epidemic subtypes of CA-MRSA within most geographic
      areas. In parts of the United States, community MRSA infections currently exceed
      those caused by their methicillin-susceptible counterparts. In Singapore, CA-MRSA
      infections are increasing, predominantly as a result of the spread of ST30
      clones. CONCLUSION: Available evidence suggests that the emergence of MRSA from
      the community is not going to be a transient phenomenon. Local guidelines for
      dealing with this phenomenon at both therapeutic and preventive levels are needed
      prior to the potential development of a situation mirroring that of meso-endemic
      HA-MRSA in local hospitals or CA-MRSA epidemics in parts of USA.

PMID- 16902725
TI  - Complications relating to intravenous buprenorphine abuse: a single institution
      case series.
AB  - INTRODUCTION: We present a retrospective descriptive study of cases admitted to
      Tan Tock Seng Hospital from March 2005 to October 2005 with complications of
      Subutex abuse. CLINICAL PICTURE: A total of 8 patients were studied. Of the 8, 7
      were male and one was female. Their complications consist of the following:
      arterial pseudoaneurysm (2), arterial pseudoaneurysm with infective venous
      thrombus (1), infective venous thrombus (1), venous thrombus (2), end arterial
      spasms (1) and sympathetic dystrophy (1). TREATMENT: For the patient who
      presented with buprenorphine-associated neuropathy, non-operative treatment with
      analgesics was given. Conservative medical therapy involving deep venous
      thrombosis treatment was instituted for the patient with deep venous thrombosis.
      Repair, restorative bypass and embolectomy surgery were performed for patients
      who had severe embolic/thrombotic complications. One of the patients who received
      the above surgery required amputation of his lower limb. OUTCOME: Of the 8
      patients, 4 were treated medically, 3 required surgery and 1 required amputation.
      Their recoveries were uneventful. Of the 8, 1 absconded and was not followed up
      with. CONCLUSION: Parenteral injection of buprenorphine can cause a wide range of
      vascular complications from simple vascular irritation to severe infective
      thrombosis and pseudoaneurysms requiring limb amputations. Non-sterile
      preparation of an injected substance or non-sterile injection sites and the
      repeated punctures of major vessels are possible culprits in those who are seen
      to have acute infection of injection sites.

PMID- 16902726
TI  - Abuse of prescription buprenorphine, regulatory controls and the role of the
      primary physician.
AB  - INTRODUCTION: Buprenorphine is an opioid partial agonist approved in several
      countries for the treatment of opioid dependence. It was approved in Singapore in
      2002 for this indication, and is more widely available in the primary care
      setting and can be prescribed by all licensed physicians who have undergone
      designated training. There is limited literature addressing the risk of its
      illicit abuse via intravenous self-administration. CLINICAL PICTURE: We report 2
      such cases of the abuse of prescription buprenorphine in the psychiatric
      consultation-liaison service of a general teaching hospital, the treatment
      approaches and outcomes. CONCLUSION: We also briefly review the indications, uses
      and abuses of buprenorphine in Singapore, and as reported in other countries, and
      the roles of primary care physicians, in order to stimulate greater awareness and
      understanding among specialists and general practitioners, who would encounter
      these patients in various settings.

PMID- 16902727
TI  - Can long-term corticosteriods lead to blindness? A case series of central serous
      chorioretinopathy induced by corticosteroids.
AB  - INTRODUCTION: Long-term, high-dose corticosteroid therapy is well-known to cause
      systemic and ocular complications. A lesser known complication is chronic central
      serous chorioretinopathy (CSCR). Although idiopathic central serous
      chorioretinopathy (CSCR) is known to be mild with spontaneous recovery and
      minimal effects on the final visual acuity, chronic CSCR as a complication of
      long- term steroid therapy behaves differently, and may cause irreversible visual
      impairment. CLINICAL PICTURE: Three cases of chronic, recurrent CSCR were
      precipitated by longterm corticosteroids prescribed for post-renal transplant
      immunosuppressive therapy, postpituitary surgery and pemphigus vulgaris.
      TREATMENT AND OUTCOME: Two cases resolved with tapering of corticosteroids while
      one case was treated by focal laser photocoagulation. Two eyes had severe
      impairment of vision as a result of subretinal scar formation while the other 4
      eyes had mild reduction of visual acuity from retinal epithelium pigment atrophy.
      CONCLUSION: Long-term corticosteroid therapy can be complicated by severe,
      chronic and recurrent CSCR and occasionally peripheral exudative retinal
      detachment. This may result in subretinal fibrosis and permanent loss of vision.

PMID- 16902728
TI  - A hyperthyroid patient with measurable thyroid-stimulating hormone concentration 
      a trap for the unwary.
AB  - INTRODUCTION: In a patient with hyperthyroidism, the detection of elevated
      thyroid hormone concentration with measurable thyroid-stimulating hormone (TSH)
      value poses considerable diagnostic difficulties. CLINICAL PICTURE: This 38-year
      old lady presented with clinical features of thyrotoxicosis. Her serum free
      thyroxine concentrations were unequivocally elevated [45 to 82 pmol/L (reference
      interval, 10 to 20 pmol/L)] but the serum TSH values were persistently within the
      reference interval [0.49 to 2.48 mIU/L (reference interval, 0.45 to 4.5 mIU/L)].
      TREATMENT: Investigations excluded a TSH-secreting pituitary adenoma and a
      thyroid hormone resistance state and confirmed false elevation in serum TSH
      concentration due to assay interference from heterophile antibodies. The patient
      was treated with carbimazole for 18 months. OUTCOME: The heterophile antibody
      mediated assay interference disappeared 10 months following the initiation of
      treatment with carbimazole, but returned when the patient relapsed. It
      disappeared again 2 months after the initiation of treatment. CONCLUSIONS:
      Clinicians should be aware of the potential for interference in immunoassays, and
      suspect it whenever the test results seem inappropriate to the patient's clinical
      state. Misinterpretation of test values, arising as a result of assay
      interference, may lead to misdiagnosis, unnecessary and at times expensive
      investigations, delay in initiation of treatment and worst of all, the initiation
      of inappropriate treatment.

PMID- 16902729
TI  - A bolt out of the blue: a case of unexpected acute liver failure.
AB  - INTRODUCTION: We describe an unusual case of acute hepatitis leading rapidly to
      acute liver failure. CLINICAL PICTURE: Our patient had known chronic hepatitis B
      with a regenerating nodule confirmed on imaging and histology. He was admitted
      initially for abdominal discomfort after a trip to China, and investigations
      showed acute hepatitis with alanine transaminase (ALT) and aspartate transaminase
      (AST) at 678 and 557 U/L, respectively. Initial differential diagnoses were acute
      exacerbations of chronic hepatitis B, and viral hepatitis A or E. However, acute
      Budd- Chiari syndrome was diagnosed on computed tomography (CT) scan of the
      abdomen, which showed extensive thrombosis of the hepatic vein, all the
      intrahepatic branches, inferior vena cava, up to the right atrium. TREATMENT: Due
      to the extensive nature of the thrombus, radiological or surgical intervention
      could not be performed. OUTCOME: The patient was managed conservatively but
      progressed rapidly and died of acute liver failure 16 days after presentation.
      CONCLUSION: Our case highlights the rapidity of progression of acute Budd-Chiari
      syndrome. Diagnosis and management of Budd-Chiari syndrome are discussed.

PMID- 16902730
TI  - Buprenorphine-associated deaths in Singapore.

PMID- 16902731
TI  - Ethical issues in ophthalmology and vision research.
AB  - As more research work is done on eye disorders, more safety rules and regulations
      are required to ensure the safety of trial subjects. This is the main function of
      Research Ethics Committees [also known as Institutional Review Boards (IRBs) and
      Domain Specific Review Boards (DSRBs)]. Tragedies in research in other fields are
      wake-up calls, such as the death of a healthy young volunteer subject in New
      York, the termination of a large study sparked by breach of medical
      confidentiality in Singapore and the South Korean debacle of its pioneering work
      in cloning. Many issues are still being debated, such as what statutory changes
      are required to control trials; whether all trials should be reviewed by IRB; if
      phase IV trials should be exempted; if compensation should be paid for all trial
      related injuries; and whether investigators and IRB members be allowed to hold
      certain amount of shares in drug or device firms. Recent measures taken to
      prevent ethical problems include funding organisations not approving a study
      unless it has been cleared by the IRB, and requiring all investigators and IRB
      members to pass an ethics course. More measures will need to be taken to ensure
      the safety of the trial subjects involved in research studies.

PMID- 16902735
TI  - Rural surgeon in Colombia.

PMID- 16902732
TI  - Relationship between insight, cognitive function, social function and
      symptomatology in schizophrenia: the West London first episode study.
AB  - OBJECTIVE: To examine the nature and clinical correlates of insight in first
      episode schizophrenia, and how these differ from findings in established
      schizophrenia. METHOD: Insight (and insight dimensions), clinical symptoms,
      neurocognitive function and social function were assessed in 94 patients with
      first-episode schizophrenia or schizophreniform disorder according to DSM-IV
      criteria. RESULTS: Greater global insight was associated with more severe
      depression. Poor overall insight was associated significantly with more severe
      negative and disorganisation symptoms as well as poor working memory, and at a
      trend level with lower current IQ. Patients with poor insight perceived
      themselves to have a better level of independent performance at daily living
      activities. CONCLUSION: In first-episode psychosis, the clinical correlates of
      poor insight are similar to those reported for established schizophrenia. Those
      patients with greater insight may be at risk of depression. The complex
      relationships between insight, positive and negative symptoms, neurocognitive
      dysfunction and social function may reflect the multidimensional nature of
      insight.

PMID- 16902733
TI  - Deliberate self-harm patients of no fixed abode: a study of characteristics and
      subsequent deaths in patients presenting to a general hospital.
AB  - BACKGROUND: International studies report high rates of deliberate self-harm (DSH)
      and suicide in the homeless. Little is known about DSH among homeless people in
      the UK and their subsequent risk of death from suicide and non-suicidal causes.
      METHOD: We have carried out a study of no fixed abode (NFA) patients using data
      collected through the Oxford Monitoring System for Attempted Suicide. We describe
      the demographic and clinical characteristics of NFA DSH patients and the findings
      of a mortality follow-up study of a cohort of these patients. RESULTS: Between
      July 1988 and December 2002, 10,346 persons presented following 17,352 DSH
      episodes. Of these persons, 374 (3.6%) were of NFA. Compared with domiciled DSH
      patients, NFA patients were more likely to be male, single, unemployed, to have
      been a recent victim of violence and violent towards others, to have a criminal
      record and to have a personality disorder. More NFA patients faced problems with
      drugs and alcohol, social isolation, finances, the law and housing and had
      received psychiatric treatment within the previous 12 months. Substantially more
      NFA patients had a past history of DSH and re-presented with a further episode of
      DSH within 12 months. In the cohort of DSH patients who presented between January
      1978 and December 1997 and who were followed up until December 2000, mortality
      from probable suicide and from all causes was approximately double that of
      domiciled patients. CONCLUSIONS: NFA DSH patients are a vulnerable group of
      patients at high risk of DSH repetition and with increased mortality from all
      causes. Good liaison between medical and psychiatric services is important.
      Specialist services may need to be developed to meet the particular needs of this
      patient group.

PMID- 16902738
TI  - Day care laparoscopic cholecystectomy: a feasibility study in a public health
      service hospital in a developing country.
AB  - BACKGROUND: Day care laparoscopic cholecystectomy (DCLC) has been shown to be
      safe in centers with adequate infrastructure for day care surgery in economically
      advanced countries. However, the feasibility of applying this concept in public
      health service hospitals in less developed and developing nation needs to
      studied. Unique protocols need to be developed and tested, taking into account
      local conditions and infrastructural constraints. PATIENTS AND METHODS: Patients
      less than 60 years old, graded I and II on the American Society of
      Anesthesiologists (ASA) physical status score, living within one hour traveling
      time and willing to make their own arrangements for a return to hospital in case
      of problems, were selected for DCLC. RESULTS: 291 cases (78%) out of 373
      laparoscopic cholecystectomies done in one calendar year were found suitable for
      DCLC. The most common cause for omitting from DCLC was that the patient lived out
      of the defined area (57%). Four of 291 (1.3%) cases were cancelled due to medical
      condition; 270/287 (96.1%) were discharged the same evening as surgery; 6
      patients were converted to open surgery; and 11 did not meet the necessary
      discharge criteria. Eight of 270 (2.9%) required readmission out of which 3
      (1.1%) required intervention. Overall, incidence of complication rate was 3.4%.
      Analysis of data showed that results were comparable to previously published
      studies, hence extrapolating that inclusion and discharge criteria used in the
      study are valid. However, there are certain social constraints which hinder truly
      universal application of DCLC. CONCLUSIONS: DCLC is a safe and technically
      feasible concept, even in public health service centers without dedicated
      ambulatory surgery units. It has potential for much economical and social benefit
      in these countries.

PMID- 16902739
TI  - Retrosternal goiter: the need for median sternotomy.
AB  - INTRODUCTION: The aim of this study was to analyze the features of patients with
      goiter who underwent thyroidectomy via a cervical incision and a median
      sternotomy in Khartoum. METHODS: A total of 267 thyroidectomies were performed in
      Khartoum Teaching Hospital during the period from January 2002 to December 2003.
      There were 40 patients with evidence of retrosternal goiter (15%). Of those 40
      patients, 13 had clinical and radiologic evidence of deep retrosternal extension
      of the goiter possibly necessitating sternotomy. Only 9 of the 13 patients
      actually required sternotomy, which accounted for 3.4% of all thyroidectomies
      performed (n = 267). The clinical, radiologic, and pathologic findings of those 9
      sternotomy patients were analyzed and compared to those of the 258 patients who
      underwent cervical thyroidecomy. RESULTS: Total thyroidectomy was undertaken in
      all nine patients. Six of them had retrosternal extension on the right side of
      the mediastinum, and three had bilateral extension. Seven patients had symptoms
      of respiratory distress, and two were asymptomatic. The duration of the goiter
      ranged between 7 and 30 years. The chest radiograph and computed tomography scan
      revealed that the retrosternal part was below the level of the aortic knuckle at
      the tracheal bifurcation in all cases. The histopathology revealed a simple
      multinodular goiter in eight of the nine patients (89%) and in one patient with
      papillary carcinoma. Five of the nine patients underwent intraoperative
      prophylactic tracheostomy due to tracheomalacia. CONCLUSIONS: A long-standing
      goiter with deep (below the aortic knuckle) mediastinal extension and tracheal
      space compromise can be postulated to increase the likelihood of sternotomy.

PMID- 16902740
TI  - Diagnosis and treatment of gastric heterotopic pancreas.
AB  - BACKGROUND: Heterotopic pancreas (HP) in the stomach can be difficult to diagnose
      and there are many treatment options. The aim of this article is to review the
      contemporary diagnosis of and treatment options for HP in the stomach. METHODS:
      We undertook a retrospective review of patients with the diagnosis heterotopic
      pancreas registered at St. Olavs University Hospital in Trondheim from 1990 to
      2002. We report on clinical findings, provide a histological review, and
      summarize the literature with particular emphasis on the diagnosis and treatment
      of HP in the stomach. RESULTS: We found 32 cases, most of them in the stomach and
      the small intestine. Sixteen patients were symptomatic. A histological
      examination showed that most of the tumors were submucosal and had the appearance
      of normal pancreas tissue. CONCLUSION: Gastric HP is not an uncommon diagnosis
      compared with many other gastric tumors and should more often be considered as a
      differential diagnosis. Symptom correlation is not always easy to determine, but
      symptom relief after treatment is well established. An endoscopic ultrasound
      examination may help when screening patients for extended biopsy and in deciding
      on which type of operation is to be performed. When treated, minimally invasive
      techniques should be applied.

PMID- 16902741
TI  - Comparison of spinal cord protection utilizing left atrial-femoral with femoral
      femoral bypass in patients with traumatic rupture of the aortic isthmus.
AB  - INTRODUCTION: Postoperative paraplegia remains a dreaded complication of repair
      of traumatic rupture of the aortic isthmus. Claims have been made that left
      atrial-femoral bypass provides better spinal cord protection. To test the
      hypothesis that left atrial-femoral bypass is better than femoral vein-to-femoral
      artery bypass in regard to postoperative paraplegia, we concurrently compared the
      two techniques. METHODS: We compared the occurrence of paraplegia in 18 patients
      whose ruptures were repaired utilizing left atrial-femoral bypass with 10,000
      units of systemic heparin (group A) and 72 patients with femoral-femoral bypass
      with heparin 300 units/kg and an oxygenator (group B) operated on between January
      1995 and July 2004. RESULTS: The mortality rate was 5.6% (5/90), with no
      statistical difference between the two groups. Postoperative paraplegia was
      present in three (16.7%) group A patients and five group B (6.9%) patients.
      However, the specific etiology of the neurologic defect was not clear, as one
      patient's paraplegia was transient following a period of cardiac arrest, and four
      others had had neurologic injuries prior to the aortic repair. Median aortic
      cross-clamp times were shorter in group A (34 minutes vs. 49 minutes). No patient
      required reexploration for bleeding, and no patient developed a graft infection.
      CONCLUSIONS: Paraplegia rates were higher in the left atrial-femoral group, but
      the difference was not statistically significant. This occurred despite the
      decreased cross-clamp times in this group. In patients undergoing repair of
      traumatic rupture of the aortic isthmus, left atrial-femoral bypass does not
      provide better spinal cord protection than femoral-femoral bypass.

PMID- 16902742
TI  - A 7-year experience with thoracoscopic sympathectomy for critical upper limb
      ischemia.
AB  - BACKGROUND: Severely symptomatic arterial insufficiency of an upper limb not
      suitable for revascularization is a difficult condition to manage. Thoracoscopic
      sympathectomy (TS) can be an effective procedure in this setting. METHODS: Our
      experience with 18 consecutive thoracoscopic sympathectomy (TS) procedures over a
      period of 7 years has been reviewed. Indications, operative technique,
      complications, and outcome of surgery are analyzed. RESULTS: We performed 18 TS
      procedures on 17 patients during this period. There were no deaths. One patient
      had intraoperative hemorrhage necessitating conversion to open thoracotomy. Mean
      postoperative hospital stay was 2.3 days. Follow-up ranged from 6 to 72 months.
      All patients demonstrated clinical benefit from the procedure. CONCLUSIONS:
      Thoracoscopic sympathectomy is a useful option in patients with severely
      symptomatic hand and digital ischemia from occlusive small arterial disease like
      thromboangitis obliterans.

PMID- 16902744
TI  - Impact of polypropylene amount on functional outcome and quality of life after
      inguinal hernia repair by the TAPP procedure using pure, mixed, and titanium
      coated meshes.
AB  - BACKGROUND: Laparoscopic inguinal hernia repair requires the use of prosthetic
      material. This prospective, single-center study was intended to investigate the
      impact of the amount of polypropylene (PP) mesh used in hernia repair on
      functional results and quality of life. METHODS: For this series, 672 consecutive
      patients with primary inguinal hernia undergoing transabdominal preperitoneal
      hernia repair (TAPP) using a heavyweight PP mesh (Prolene 10 x 15 cm, 1.5 g,
      group I, n = 232), a mixed PP- and Polyglactin mesh (Vypro II, 10 x 15 cm, 0.53
      g, group II, n = 217), or a light-weight titanized PP mesh (Ti-Mesh, 10 x 15 cm,
      0.24 g, group III, n = 223) were compared in terms of postoperative complications
      (seroma, wound healing disorders), quality of life score (pain development,
      physical condition, urologic disorders), and hernia recurrence. RESULTS: During a
      12-month follow-up there were no significant differences in the recurrence rate
      (1.3%-1.7%). Patients with a pure PP mesh (group I) showed significantly more
      postoperative seromas (12.1% versus 4.1%/1.8%), foreign body sensations (9.1%
      versus 5.5%/3.5%), and sensitivity to weather changes (5.6% versus 3.2%/2.2%)
      compared to groups II and III. In all groups, the quality of life score was
      improved postoperatively. However, among those patients in our series with few
      preoperative complaints, the postoperative quality of life was worsened when
      heavy-weight PP meshes (group I+II) were used but significantly improved when
      light-weight titanized PP meshes were used. CONCLUSIONS: Comparable functional
      results, fewer postoperative complications, and improved quality of life can be
      achieved by reducing the amount of PP in meshes used for laparoscopic hernia
      repair by TAPP procedure.

PMID- 16902745
TI  - Procedure-specific systematic review and consensus recommendations for
      postoperative analgesia following laparoscopic cholecystectomy.

PMID- 16902746
TI  - VersaStep trocar hernia rate in unclosed fascial defects in bariatric patients.
AB  - OBJECTIVE: Use of the VersaStep trocar system (US Surgical, Norwalk, CT) has the
      perceived advantage of minimal trocar-related hernias in patients undergoing Roux
      en-Y gastric bypass surgery (RYGB). We performed a retrospective review of our
      last 747 consecutive operative procedures using these trocars. METHODS AND
      PROCEDURES: The patient population was 747 consecutive patients who underwent
      laparoscopic RYGB at Duke University Health System Weight Loss Surgery Center
      from January 2002 through April 2005. A total of 3735 radially expanded trocar
      sites were used. VersaStep trocars were used in all cases. The port configuration
      included one supraumbilical Hasson port, two 12-mm ports, and three 5-mm ports.
      The Hasson port was closed with a figure-of-eight number 1 Polysorb suture. All
      other trocar sites had no fascial closure. Intestinal anastomoses were created
      with a linear stapler in all of the laparoscopic cases, with hand suturing of the
      residual enterotomy. The fascial incisions were therefore not extended to
      accommodate an EEA stapler. The charts were reviewed for occurrence of subsequent
      trocar site hernias. RESULTS: There were no hernias at any of the VersaStep
      trocar sites-an incidence of 0%. There were nine incisional hernias at the Hasson
      port site which later required surgical repair-an incidence of 1.20%.
      CONCLUSIONS: There were no hernias detected at any of the 1494 12-mm or 2241 5-mm
      VersaStep trocar sites, despite lack of suture closure. At the Hasson port site,
      there was a hernia incidence of 1.20%. In the bariatric RYGB population, routine
      suture closure of the fascia or muscle is not necessary when using radially
      expanding VersaStep trocars.

PMID- 16902747
TI  - Laparoscopically assisted liver biopsy with a hemostatic plug.
AB  - BACKGROUND: Percutaneous and open liver biopsies are routine procedures for
      diagnosing liver pathology. However, the procedure can carry significant
      morbidity and even mortality, especially in the event of an uncorrectable
      coagulopathy or a highly vascular tumor. METHODS: A technique described for use
      in such circumstances involves laparoscopy for identification of the lesion to be
      biopsied, enables placement of a gelatin hemostatic plug in the core biopsy
      tract, and confirms hemostasis after percutaneous plugging of the biopsy site.
      RESULTS: The technique was successfully used for seven patients: six patients
      with hepatic coagulopathy and one with a highly vascular liver tumor. There were
      no complications during either the intra- or postoperative period. The patients
      experienced minimal postoperative discomfort and returned to baseline activity on
      the first postoperative day. CONCLUSION: The authors believe that the described
      technique of biopsy site plugging offers a safe alternative for liver biopsy
      among patients with an uncorrectable coagulopathy and those requiring a biopsy
      before correction of the bleeding disorder.

PMID- 16902748
TI  - Pregnancy after laparoscopic adjustable gastric banding: perinatal outcome is
      favorable also for women with relatively high gestational weight gain.
AB  - BACKGROUND: The prevalence of morbid obesity is increasing steadily among women
      of reproductive age. In addition to the well-known comorbidities of the disease,
      it has been shown that the pregnancy outcome for obese women is worse than for
      women with a normal body mass index. This study aimed to evaluate the pregnancy
      and perinatal outcomes for women who underwent laparoscopic adjustable gastric
      banding (LAGB) because of morbid obesity. METHODS: This prospective, population
      based study was conducted in a general surgery clinic of a tertiary hospital
      serving as a referral center for bariatric operations. All the patients underwent
      LAGB by the pars flaccida technique. A database containing information regarding
      age, pre- and postoperative weight and body mass index, weight gain, and LAGB
      related or -unrelated complications during pregnancy was constructed for all
      women of childbearing age who underwent LAGB. A questionnaire was designed to
      provide perinatal data concerning both mother and neonate. RESULTS: The 74 women
      enrolled in this study had 81 single tone pregnancies. Their body mass index
      decreased significantly after LAGB, from 43.3 +/- 5.8 to 30.3 +/- 3 kg/m2 at
      conception (p < 0.0001). The average time to the first live birth after surgery
      was 27 +/- 3 months. Band slippage was diagnosed and treated laparoscopically in
      two patients (2.4%). Weight gain during pregnancy was 10.6 +/- 2.1 kg. The rates
      of pregnancy-induced hypertension and gestational diabetes were 7.4% and 16% of
      all pregnancies, respectively. In 17 cases (20%), cesarean section was performed.
      Delivery occurred after 39.1 weeks of gestation. The mean birth weight was 3.09
      +/- 0.5 kg. Major congenital anomalies, postnatal hypoglycemia, symptomatic
      polycythemia or neonatal death were not recorded. CONCLUSIONS: The findings show
      that LAGB is safe for both mother and newborn during gestation and delivery.

PMID- 16902749
TI  - Laparoscopic redo Nissen fundoplication in infants and children.
AB  - From January 1994 to December 2004, 118 patients with recurrent gastroesophageal
      reflux disease (GERD) after fundoplication underwent laparoscopic redo Nissen
      fundoplication. The patients ranged in age from 6 months to 19 years (mean, 7
      years), and weighed from 6.4 to 85 kg. Of the 118 patients, 64 had previous open
      fundoplications, 53 had previous laparoscopic fundoplications, and 19 had more
      than one previous fundoplication. All the procedures had been successfully
      completed laparoscopically. The average operative time was 100 min. The
      intraoperative complication rate was 1.1%. The average time to full feeding was
      1.8 days, and the average hospital stay was 2.2 days. The postoperative
      complication rate was 3.6%. The wrap failure rate during an average follow-up
      period of 48 months was 6%. Laparoscopic redo Nissen fundoplication for a failed
      antireflux procedure is a safe and effective procedure. It has the same benefits
      as a primary laparoscopic Nissen for GERD, with low morbidity and a quicker
      recovery. Early follow-up evaluation suggests that the long-term outcome is
      superior to that associated with open redo fundoplication.

PMID- 16902750
TI  - Virtual reality simulator training equals mechanical robotic training in
      improving robot-assisted basic suturing skills.
AB  - BACKGROUND: This study aimed to investigate the effect of a virtual reality
      simulator on the learning of basic robotic suturing skills. METHODS: Two
      randomized groups of students underwent a controlled training program. Both
      groups completed an identical test before and after training. The increase in the
      number of stitches placed during the pretest and posttest was used as an
      objective measure of the training effect. To evaluate the subjective feeling of
      understanding and mastering, the students indicated this on a visual analog
      scale. RESULTS: Both groups showed a significant increase in the number of
      stitches placed during the posttest, and an increase in subjective feeling of
      understanding and mastering. The increase did not differ between the groups,
      indicating that the virtual reality simulator equaled the mechanical trainer in
      training of robotic suturing technique. CONCLUSIONS: Training in basic robot
      assisted suturing skills using a virtual reality simulator without additional
      training equaled training using a mechanical simulator.

PMID- 16902752
TI  - Nocardia gamkensis sp. nov.
AB  - A novel actinomycete, strain CZH20(T), was isolated from a soil sample taken from
      the banks of the Gamka River in the Swartberg Nature Reserve, Western Cape
      Province, South Africa. Strain CZH20(T) was identified as a member of the genus
      Nocardia by a polyphasic approach. Strain CZH20(T) could be differentiated from
      other members of the genus Nocardia on the basis of physiology and 16S-rRNA gene
      sequence analysis. It exhibited weak antibiosis against Mycobacterium aurum A+.
      Organic solvent extracts of the culture filtrate and mycelial mass of CZH20(T)
      exhibited moderate antibiotic activity against Mycobacterium smegmatis LR222 and
      Mycobacterium tuberculosis H37Rv. The name Nocardia gamkensis is proposed, with
      the type strain CZH20(T) (=DSM 44956(T) =NRRL B-24450(T)).

PMID- 16902751
TI  - Compartmentalized cAMP/PKA signalling regulates cardiac excitation-contraction
      coupling.
AB  - The sympathetic control over excitation-contraction coupling (ECC) is mediated by
      the cAMP/PKA signalling pathway. However, in the myocyte, the same signalling
      pathway is responsible for triggering a plethora of diverse intracellular
      functions the control of which must be independent of the regulation of ECC. Here
      we discuss what are the molecular mechanisms leading to selective modulation of
      ECC in cardiac myocytes with a particular focus on the role of spatial
      confinement of PKA subsets and the compartmentalization of cAMP.

PMID- 16902753
TI  - Sequential and structural analysis of [NiFe]-hydrogenase-maturation proteins from
      Desulfovibrio vulgaris Miyazaki F.
AB  - The complete primary structure of the hyn-region in the genome of Desulfovibrio
      vulgaris Miyazaki F (DvMF), encoding the [NiFe]-hydrogenase and two maturation
      proteins has been identified. Besides the formerly reported genes for the large
      and small subunits, this region comprises genes encoding an endopeptidase (HynC)
      and a putative chaperone (HynD). The complete genomic region covers 4086
      nucleotides including the previously published upstream located promoter region
      and the sequences of the structural genes. A phylogenetic tree for both
      maturation proteins shows strongest sequential relationship to the orthologous
      proteins of Desulfovibrio vulgaris Hildenborough (DvH). Secondary structure
      prediction for HynC (168 aa, corresponding to a molecular weight of 17.9 kDa)
      revealed a practically identical arrangement of alpha-helical and beta-strand
      elements between the orthologous protein HybD from E. coli and allowed a three
      dimensional modelling of HynC on the basis of the formerly published structure of
      HybD. The putative chaperone HynD consists of 83 aa (molecular weight of 9 kDa)
      and shows 76% homology to DvH HynD. Preliminary experiments demonstrate that the
      operon is expressed under the control of its own promoter in Escherichia coli,
      although no further processing could be observed, providing evidence that
      additional proteins have to be involved in the maturation process. Accession
      numbers: DQ072852, HynC protein ID AAY90127, HynD protein ID AAY90128.

PMID- 16902754
TI  - High genetic variability of the Streptococcus thermophilus cse central part, a
      repeat rich region required for full cell segregation activity.
AB  - The cse gene of Streptococcus thermophilus encodes an extracytoplasmic protein
      involved in cell segregation. The Cse protein consists of two putative domains: a
      cell wall attachment LysM domain and a catalytic CHAP domain. These two domains
      are spaced by an interdomain linker, known as Var-Cse, previously reported to be
      highly divergent between two S. thermophilus strains. The aim of this study was
      to assess the extent of this intraspecific variability and the functional
      involvement of the var-cse region in cell segregation. Analysis of the var-cse
      sequence of 19 different strains allowed detection of 11 different alleles,
      varying from 390 bp to 543 bp, all containing interspersed and tandem nucleotides
      repeats. Overall, 11 different repeat units were identified and some series of
      these small repeats, named supermotifs, form large repeats. Results suggested
      that var-cse evolved by deletion of all or part of the repeats and by duplication
      of repeats or supermotifs. Moreover, sequence analysis of the whole cse locus
      revealed that the cse ORF is mosaic suggesting that var-cse polymorphism resulted
      from horizontal transfer. The partial deletion of the var-cse region of the S.
      thermophilus strain CNRZ368 led to the lengthening of the number of cells per
      streptococcal chain, indicating that this region is required for full cell
      segregation in S. thermophilus strain CNRZ368.

PMID- 16902755
TI  - Identification of species in the genus Pichia by restriction of the internal
      transcribed spacers (ITS1 and ITS2) and the 5.8S ribosomal DNA gene.
AB  - In this study, the variability within the ribosomal DNA region spanning the
      internal transcribed spacers ITS1 and ITS2 and the 5.8S gene (5.8S-ITS rDNA) was
      used to differentiate species in the genus Pichia. The 5.8S-ITS rDNA region was
      PCR-amplified and the PCR product digested with the enzymes CfoI, HinfI, and
      HaeIII. The variability in the size of the amplified product and in the
      restriction patterns enabled differentiation between species in the genus Pichia,
      and between Pichia species and yeast species from other genera in the Yeast-id
      database ( http://www.yeast-id.com/ ). Moreover, the restriction fragment length
      polymorphism (RFLP) patterns of the 5.8S-ITS enabled misidentified strains to be
      detected and revealed genetic heterogeneity between strains within the Pichia
      membranifaciens and Pichia nakazawae species. Ultimately, the RFLP patterns of
      the 5.8S-ITS rDNA failed to differentiate between some Pichia and Candida species
      that could be distinguished on the basis of the sequence of the 5.8S-ITS rRNA
      region or the sequence of the D1/D2 domain of the 26S rDNA gene.

PMID- 16902756
TI  - A thin-film model for corotational Jeffreys fluids under strong slip.
AB  - We derive a thin-film model for viscoelastic liquids under strong slip which obey
      the stress tensor dynamics of corotational Jeffreys fluids.

PMID- 16902757
TI  - Clinical and densitometric efficacy of the association of interferon alpha and
      pamidronate in the treatment of osteoporosis in patients with systemic
      mastocytosis.
AB  - Osteoporosis accompanying severe mastocytosis leads to numerous compressed
      vertebrae. We treated four patients (mean age 52 years) with severe osteoporosis
      and mastocytosis proven by bone marrow biopsy (more than 40 mast cells/mm3),
      according to the following protocol: interferon alpha (IFN) 3 million units (MU)
      three times a week, reduced to 1.5 MU three times a week in the event of
      intolerance, and pamidronate (Pam) 90 mg/month in infusion. This treatment was
      given for 2 years. It was followed by Pam alone at a dose of 90 mg/month. After 3
      or 4 years of treatment, no patient presented new vertebral or extravertebral
      fractures. The mean increase in bone mineral density (BMD) with IFN and Pam was
      16.05+/-6.12% at the spine, 5+/-2.24% at the femoral neck, and 4.12+/-3.03% for
      the whole body; the increase or loss of BMD with Pam alone was +0.2+/-2.13% at
      the spine, -2.25+/-2.78% at the femoral neck, and -0.1+/-3.35% for the whole
      body. In one patient, the IFN dose was halved because of a flu-like syndrome, and
      in another IFN was discontinued at one year for the same reason. The association
      of IFN and Pam led to a major increase in bone marrow density in osteoporosis
      with concomitant mastocytosis and this gain was then maintained by monthly
      infusions of Pam.

PMID- 16902759
TI  - The calcium binding proteins calbindin, parvalbumin, and calretinin have specific
      patterns of expression in the gray matter of cat spinal cord.
AB  - Calcium binding proteins (CBPs) regulate intracellular levels of calcium (Ca(2+))
      ions. CBPs are particularly interesting from a morphological standpoint, because
      they are differentially expressed in certain sub-populations of cells in the
      nervous system of various species of vertebrate animals. However, knowledge on
      the cellular regulation governing such cell-specific CBP expression is still
      incomplete. In this work on the L7 segment of the cat spinal cord, we analyzed
      the localization and morphology of neurons expressing the CBPs calbindin-28 KD
      (CB), parvalbumin (PV), and calretinin (CR), and co-expressing CB and PV, CB and
      CR, and PV and CR. Single CBP-positive ((+)) neurons showed specific
      distributions: (1) CB was present in small neurons localized in laminae I, II,
      III and X, in small to medium size neurons in laminae III-VI, and in medium to
      large neurons in laminae VI-VIII; (2) PV was present in small size neurons in
      laminae III and IV and in medial portions of laminae V and VI, medium neurons and
      in lamina X at the border with lamina VII, in medium to large neurons in laminae
      VII and VIII; (3) CR labeling was detected in small size neurons in laminae I,
      II, III and VIII, in medium to large size neurons in laminae I and III-VII, and
      in small to medium size neurons in lamina X. Double labeled neurons were a small
      minority of the CBP(+) cells. Co-expression of CB and PV was seen in 1 to 2% of
      the CBP(+) cells, and they were detected in the ventral and intermediate portions
      of lamina VII and in lamina X. Co-localization of CB and CR was present in 0.3%
      of the cells and these cells were localized in lamina II. Double labeling for PV
      and CR occurred in 6% of the cells, and the cells were localized in ventral part
      of lamina VII and in lamina VIII. Overall, these results revealed distinct and
      reproducible patterns of localization of the neurons expressing single CBPs and
      co-expressing two of them. Distinct differences of CBP expression between cat and
      other species are discussed. Possible relations between the cat L7 neurons
      expressing different CBPs with the neurons previously analyzed in cat and other
      animals are suggested.

PMID- 16902760
TI  - Acetylcholine receptors and nerve terminal distribution at the neuromuscular
      junction of long-term regenerated muscle fibers.
AB  - Mdx mice are deficient in dystrophin and show muscle fiber regeneration. Changes
      in the distribution of acetylcholine receptors have been reported at the
      neuromuscular junction of mdx mice and may be a consequence of muscle fiber
      regeneration. In this study, we examined whether the distribution of receptors
      was still altered in long-term, regenerated muscle fibers from C57Bl/10 mice. The
      left sternomastoid muscle of adult mice was injected with 60 microl of lidocaine
      hydrochloride to induce muscle degeneration-regeneration. In some mice, the
      sternomastoid muscle was denervated at the time of lidocaine injection. After 90
      and 150 days, the nicotinic acetylcholine receptors were labeled with rhodamine
      alpha-bungarotoxin for confocal microscopy. At both intervals studied, the
      receptors were distributed in spots. In denervated-regenerated fibers, the
      receptors were distributed as regular branches similar to denervated muscles
      without lidocaine treatment. These findings suggested that nerve-dependent
      mechanisms were involved in the changes in receptor distribution seen in
      regenerated muscle fibers after lidocaine treatment, and that a similar
      phenomenon could explain the changes in receptor distribution seen in dystrophic
      muscle fibers.

PMID- 16902761
TI  - Progressive white matter pathology in the spinal cord of transgenic mice
      expressing mutant (P301L) human tau.
AB  - Transgenic mice expressing mutant (P301L) tau develop paresis, neurofibrillary
      tangles and neuronal loss in spinal motor neurons beginning at 4 to 6 months of
      age. Astrocytes and oligodendrocytes acquire filamentous tau inclusions at later
      ages. Here we report pathology in the spinal white matter of these animals.
      Progressive white matter pathology, detected as early as 2 months of age, was
      most marked in lateral and anterior columns, with sparing of posterior columns
      until late in the disease. Early changes in Luxol fast blue/periodic acid Schiff
      (LFB/PAS) and toluidine blue stained sections were vacuolation of myelin followed
      by accumulation of myelin figures within previous axonal tubes and finally influx
      of PAS-positive macrophages. Myelin debris and vacuoles were found in
      macrophages. At the ultrastructural level, myelinated axons showed extensive
      vacuolation of myelin sheaths formed by splitting of myelin lamellae at the intra
      period line, while axons were atrophic and contained densely packed
      neurofilaments. Other axons were lost completely, resulting in collapse and
      phagocytosis of myelin sheaths. Also present were spheroids derived from swollen
      axons with thin myelin sheaths containing neurofilaments, tau filaments and
      degenerating organelles. Many oligodendrocytes had membrane-bound cytoplasmic
      bodies composed of tightly stacked lamellae capped by dense material. The
      vacuolar myelopathy in this model to some extent resembles that reported in
      acquired immune deficiency syndrome and vitamin B12 deficiency. The progressive
      axonal pathology is most consistent with a dying-back process caused by abnormal
      accumulation of tau in upstream neurons, while vacuolar myelinopathy may be a
      secondary manifestation of neuroinflammation.

PMID- 16902762
TI  - Potassium currents in primary cultured astrocytes from the rat corpus callosum.
AB  - The corpus callosum (CC) is the main white matter tract in the brain and is
      involved in interhemispheric communication. Using the whole-cell voltage-clamp
      technique, a study was made of K(+)-currents in primary cultured astrocytes from
      the CC of newborn rats. These cells were positive to glial fibrillary acidic
      protein after culturing in Dulbecco's Modified Eagle Medium (> 95% of cells) or
      in serum-free neurobasal medium with G5 supplement (> 99% of cells). Astrocytes
      cultured in either medium displayed similar voltage-activated ion currents. In
      81% of astrocytes, the current had a transient component and a sustained
      component, which were blocked by 4-aminopyridine and tetraethylammonium,
      respectively; and both had a reversal potential of -66 mV, indicating that they
      were carried by K(+) ions. Based on the Ba(2+)-sensitivity and activation
      kinetics of the K(+)-current, two groups of astrocytes were discerned. One group
      (55% of cells) displayed a strong Ba(2+) blockade of the K(+)-current whose
      activation kinetics, time course of decay, and the current-voltage relationship
      were modified by Ba(2+). This current was greatly blocked (52%) by Ba(2+) in a
      voltage-dependent way. Another group (45% of cells) presented weak Ba(2+)
      blockade, which was only blocked 24% by Ba(2+). The activation kinetics and time
      course of decay of this current component were unaffected by Ba(2+). These
      results may help to understand better the roles of voltage-activated K(+)
      currents in astrocytes from the rat CC in particular and glial cells in general.

PMID- 16902763
TI  - Reduction in parvalbumin expression in the zona incerta after 6OHDA lesion in
      rats.
AB  - In an effort to understand better the neurochemical changes that occur in
      Parkinson disease, we have examined the expression patterns of the calcium
      binding protein parvalbumin in the zona incerta in parkinsonian rats. Sprague
      Dawley rats had small volumes of either saline (control) or 6 hydroxydopamine
      (6OHDA) injected into the medial forebrain bundle, the major tract carrying
      dopaminergic nigrostriatal axons. After various post-lesion survival periods,
      ranging from 2 hrs to 84 days, rats were perfused with formaldehyde and their
      brains processed for routine tyrosine hydroxylase (TH) or parvalbumin
      immunocytochemistry. In the 3 to 84 days post-lesion cases, there was an overall
      50% reduction in the number of parvalbumin(+) cells in the zona incerta on the
      6OHDA-lesioned side when compared to control. In the 2 hrs post-lesion cases,
      there was no substantial loss of parvalbumin(+) cells in the zona incerta after
      6OHDA lesion, although in these cases (unlike the longer survival periods), there
      was limited loss of TH(+) cells in the midbrain on the lesion side. The loss of
      parvalbumin(+) cells from the zona incerta was due to a loss of antigen
      expression rather than a loss of the cells themselves, since the number of Nissl
      stained cells in the zona incerta was similar on the control and 6OHDA-lesioned
      sides. In summary, our results indicate that a loss of the midbrain dopaminergic
      cells induces a major change in parvalbumin expression within the zona incerta.
      This change may have key functional and clinical implications.

PMID- 16902764
TI  - Immunogold study of effects of prenatal exposure to lipopolysaccharide and/or
      valproic acid on the rat blood-brain barrier vessels.
AB  - The involvement of blood microvessels, representing the anatomic site of the
      blood-brain barrier (BBB), in brain damage induced by prenatal exposure to
      lipopolysaccharide (LPS) and/or valproic acid (VPA) was studied in four-week-old
      rats. The immunogold procedure was applied for localization at the
      ultrastructural level of endogenous albumin and glucose transporter (GLUT-1) in
      three brain regions: cerebral cortex, cerebellum and hippocampus. Four groups of
      rats were used: (1) untreated control, (2) prenatally VPA-treated, (3) prenatally
      LPS-treated, and (4) prenatally LPS- and VPA-treated. The functional state of the
      BBB was evaluated as follows: (a) by its tightness, i.e., permeability to blood
      borne albumin, and (b) by the expression of GLUT-1 in the endothelial cells
      (ECs). Using morphometry, the labelling density for GLUT-1 was recorded over
      luminal and abluminal plasma membranes of the ECs, also providing information on
      their functional polarity. No extensive increase of vascular permeability and/or
      any considerable dysfunction of the BBB in experimental groups nos. 2 and 3 were
      observed, although in solitary vascular profiles, increased endocytosis or even
      transcytosis of albumin by ECs was noted. In experimental group no. 4, some
      vascular profiles showed scanty leakage (microleakage), manifested by the
      presence of immunosignals for albumin in the perivascular area. Although some
      fluctuations in the expression of GLUT-1 occurred in all experimental groups,
      especially in group no. 3, a most pronounced and significant diminution of the
      labelling density, in all three regions of the brain, was observed in group no.
      4. This finding suggests the synergistic action of prenatally applied LPS and VPA
      that affects specific transport functions of glucose in the microvascular
      endothelium. The diminished or disturbed supply of glucose to selected brain
      regions can be one of the factors leading to previously observed behavioral
      disturbances in similarly treated rats.

PMID- 16902765
TI  - Distribution of calcium-independent phospholipase A2 (iPLA 2) in monkey brain.
AB  - The present study was carried out to elucidate the distribution of calcium
      independent phospholipase A(2) (iPLA(2)) in the normal monkey brain. iPLA(2)
      immunoreactivity was observed in structures derived from the telencephalon,
      including the cerebral neocortex, amygdala, hippocampus, caudate nucleus,
      putamen, and nucleus accumbens, whereas structures derived from the diencephalon,
      including the thalamus, hypothalamus and globus pallidus were lightly labeled.
      The midbrain, vestibular, trigeminal and inferior olivary nuclei, and the
      cerebellar cortex were densely labeled. Immunoreactivity was observed on the
      nuclear envelope of neurons, and dendrites and axon terminals at electron
      microscopy. Western blot analysis showed higher levels of iPLA(2) protein in the
      cytosolic, than the nuclear fraction, but little or no protein in the membrane
      fraction. Similarly, subcellular fractionation studies of iPLA(2) activity in rat
      brain cortical cell cultures showed greater enzymatic activity in the cytosolic,
      than the nuclear fraction, and the least activity in non-nuclear membranes. The
      association of iPLA(2) with the nuclear envelope suggests a role of the enzyme in
      nuclear signaling, such as during neuronal proliferation and differentiation or
      death. In addition, the localization of iPLA(2) in dendrites and axon terminals
      suggests a role of the enzyme in neuronal signaling.

PMID- 16902766
TI  - Increase of NG2-positive cells associated with radial glia following traumatic
      spinal cord injury in adult rats.
AB  - In the CSN including the spinal cord, NG2 proteoglycan is a marker of
      oligodendrocyte progenitors. To elucidate the dynamics of the endogenous neural
      stem (progenitor) cells in adult rats with spinal cord injury (SCI), we examined
      an immunohistochemical analysis of NG2, GFAP, and 3CB2, a specific marker of
      radial glia (RG). SD rats were divided into a SCI group (n = 25) and a sham
      operated group (n = 5). In the injury group, laminectomy was performed at Th11-12
      and contusive compression injury was created by applying a weight of 30 g for 10
      min. Rats were sacrificed at 24 h, and 1, 4, 8 and 12 weeks post-injury. Frozen
      20-mu m sections of tissue 5 and 10 mm rostral and caudal to the epicenter of
      injury were prepared. Immunohistochemistry was performed using antibodies against
      NG2, GFAP and 3CB2. At 4 weeks after injury, NG2-positive glial cells arose from
      below the pial surface as bipolar cells with processes extending throughout the
      entire white matter. NG2 expression peaked at 4 weeks after injury, showing a 7
      fold increase compared to the 24 h after injury. The NG2-positive cells with
      processes which increased in the white matter of the spinal cord were GFAP
      positive and also co-localized with 3CB2 antigen. The pattern of NG2 expression
      of these cells was temporally and spatially different from the pattern of NG2
      expression that accumulated around the hemorrhagic and necrotic epicenter. These
      results suggest that NG2 positive cells which derived from subpial layer, may
      have some lineage to RG after SCI in adult rodents.

PMID- 16902767
TI  - GABA-immunoreactive neurons and terminals in the cat periaqueductal gray matter:
      a light and electron microscopic study.
AB  - Immunocytochemical and electron microscopic methods were used to study the
      GABAergic innervation in adult cat periaqueductal gray matter (PAG). A mouse
      monoclonal antibody against gamma -aminobutyric acid (GABA) was used to visualize
      the inhibitory neuronal system of PAG. At light microscopy, GABA-immunopositive
      (GABA(IP)) neurons formed two longitudinally oriented columns in the dorsolateral
      and ventrolateral PAG that accounted for 36% of the neuronal population of both
      PAG columns; their perikaryal cross-sectional area was smaller than that of
      unlabeled (UNL) neurons found in the same PAG subdivisions. At electron
      microscopic level, patches of GABA immunoreactivity were readily detected in
      neuronal cell bodies, proximal and distal dendrites, axons and axon terminals.
      Approximately 35-36% of all terminals were GABA(IP); they established symmetric
      synapses with dendrites (84.72% of the sample in the dorsolateral PAG and 86.09%
      of the sample in the ventrolateral PAG) or with cell bodies (7-10% of the
      sample). Moreover, 49.15% of GABA(IP) axon terminals in the dorsolateral and
      52.16% in the ventrolateral PAG established symmetric synapses with GABA(IP)
      dendrites. Immunopositive axon terminals and unlabeled terminals were also
      involved in the formation of a complex synaptic arrangment, i.e. clusters of
      synaptic terminals in close contact between them that were often observed in the
      PAG neuropil. Moreover, a fair number of axo-axonic synapses between GABA(IP)
      and/or UNL axon terminals were present in both PAG subdivisions. Several dendro
      dendritic synapses between labeled and unlabeled dendrites were also observed in
      both PAG subdivisions. These results suggest that in the cat PAG there exist at
      least two classes of GABArgic neurons. The first class could exert a tonic
      control on PAG projecting neurons, the second could act on those GABAergic
      neurons that in turn keep PAG projecting neurons under tonic inhibition. The
      functional implications of this type of GABAergic synapse organization are
      discussed in relation to the dishinibitory processes that take place in the PAG.

PMID- 16902768
TI  - Genotoxic effect of Goeckerman regimen of psoriasis.
AB  - Goeckerman regimen (GR) of psoriasis includes daily dermal application of crude
      coal tar (CCT) and dermal exposure to UV-A and UV-B radiation. Observed group
      consisted of 23 patients with psoriasis treated by GR. Therapeutic ointment
      contained 5% of CCT. The level of psoriasis area and severity index was
      significantly decreased after GR (P < 0.001) and confirms high efficiency of GR.
      High levels of selected metabolites of pyrene and phenanthrene indicated high
      level of dermal penetration. We found significantly increased urinary
      mutagenicity in samples collected in the middle and in the end of GR (TA98+S9, P
      < 0.01; YG1041-S9, P < 0.001; YG1041+S9, P < 0.001). Significant increasing of
      chromosomal aberrations in peripheral lymphocytes (CA) in blood samples collected
      in the end of GR (P < 0.001) and consecutive decreasing of CA in 78th day after
      the end of GR has been observed. Almost all results indicated that the patients
      could be endangered by a peak genotoxic exposure. Nevertheless, the genotoxic
      effect does not seem to be long lasting. Despite conflicting results from cancer
      epidemiological studies, it is evident that single GR can contribute to the total
      load of environmental mutagens in a group of treated patients.

PMID- 16902769
TI  - Novel hMSH2, hMSH6 and hMLH1 gene mutations and microsatellite instability in
      sporadic colorectal cancer.
AB  - PURPOSE: To detect the hMSH2, hMSH6 and hMLH1 DNA mismatch repair gene mutations
      and microsatellite instability in somatic colorectal cancer. PATIENTS AND
      METHODS: The mutations of hMSH2, hMSH6, and hMLH1 genes, including microsatellite
      instability of BAT-26, BAT-40, D2S123, D5S346 and D17S250 were analyzed in 31
      patients with colorectal. RESULTS: The results revealed that eight cases (25.8%)
      harbored mutations in DNA mismatch repair genes. Of these, five novel mutations
      including I237V in exon 4 of hMSH2, ins T at codon 1196 in exon 7 of hMSH6, and
      ins G at codon 154 in exon 6, N158H in exon 6, and del A at codon 257 in exon 9
      of hMLH1 were identified. Moreover, several intronic polymorphisms, including c-g
      transversion at IVS-1 nt211 + 9 of hMSH2, del T in poly T track at IVS-6 nt3559
      5, ATCT duplicate in IVS-7 nt 3642 + 35 and t-g transversion at IVS-10 nt4080 +
      185 of hMSH6 were demonstrated in these patients. In addition, seven cases
      (22.5%) exhibited microsatellite instability (MSI). CONCLUSION: These results
      suggested that the inactivation of DNA mismatch repair genes and microsatellite
      instability may play a minor role in somatic colorectal cancer development.

PMID- 16902770
TI  - The effects of chronic buprenorphine on intake of heroin and cocaine in rats and
      its effects on nucleus accumbens dopamine levels during self-administration.
AB  - RATIONALE: Buprenorphine reduces both heroin and cocaine intake in opioid
      addicts, but the mechanisms remain unclear. OBJECTIVES: To determine the effects
      of chronic buprenorphine treatment on intake of heroin and/or cocaine and measure
      nucleus accumbens (NAc) dopamine (DA) levels during self-administration. METHODS:
      In experiment 1, plasma levels of buprenorphine were determined in rats with
      buprenorphine osmotic minipumps (3.0 mg/kg/day) using an ELISA. In experiment 2,
      rats self-administered (FR1) one dose of heroin [(0.025, 0.05, or 0.1
      mg/kg/infusion (inf)] and one dose of cocaine (0.25, 0.5, or 1.0 mg/kg/inf)
      before and under sham or chronic buprenorphine treatment (1.5 or 3.0 mg/kg/day).
      In experiment 3, the effect of sham or chronic buprenorphine treatment (3.0) on
      heroin (0.05 mg/kg/inf) or cocaine (0.5 mg/kg/inf) self-administration under FR5
      and progressive ratio (PR) schedules was evaluated. In experiment 4, in vivo
      microdialysis sampling from the NAc was carried out during heroin (0.05
      mg/kg/inf) or cocaine (0.5 mg/kg/inf) self-administration (FR1) under sham or
      buprenorphine treatment (3.0). RESULTS: Buprenorphine levels in plasma were
      stable over time. Buprenorphine treatment had no effect on total heroin intake at
      any dose or under any schedule, whereas it suppressed cocaine intake at all doses
      and under all schedules. Buprenorphine enhanced basal levels of DA, attenuated
      the NAc DA response to heroin, and enhanced the DA response to cocaine. It is
      interesting to note that buprenorphine increased the latency to respond to drug
      associated cues at the start of self-administration sessions. CONCLUSIONS:
      Chronic buprenorphine reduces cocaine, but not heroin, intake and possibly
      reduces drug seeking by reducing the salience of the drug-associated cues.

PMID- 16902771
TI  - The effect of alcohol and repetition at encoding on implicit and explicit false
      memories.
AB  - RATIONALE: Alcohol impairs explicit memory, whilst leaving implicit memory
      relatively intact. Less is known about its effects on false memories. AIM: The
      present study examines the effects of alcohol on explicit and implicit false
      memories using study list repetition as a tool for modulating learning at
      encoding. METHODS: Thirty-two participants were given either an alcohol (0.6
      g/kg) or placebo beverage before undergoing an encoding phase consisting of 10
      lists of nine associated words (veridical items). Each list was associated to a
      word, which was not presented at encoding (semantically associated non-studied
      lure; critical item), serving as the measure for false memory. Half of the lists
      were presented once, and half were repeated three times. The next day,
      participants underwent an implicit (stem completion and post hoc awareness
      measurements), and an explicit (free recall) task. RESULTS: Alcohol decreased
      veridical and false explicit memory for singularly presented lists compared to
      placebo; no group difference existed for repeated lists. Implicit veridical
      memory was not affected by alcohol. Awareness memory measures demonstrated in
      placebo participants an increased ability with repetition in rejecting false
      memories. The reverse was found in intoxicated participants who with repetition
      accepted more false memories. CONCLUSION: Alcohol appears to decrease semantic
      activation leading to a decline in false memories. Increased learning with
      repetition, which increases the rejection of false memories under placebo, is
      reversed under alcohol leading to a decrease in rejection of false memories. The
      latter effect of alcohol may be due to its ability to impair monitoring processes
      established at encoding.

PMID- 16902772
TI  - Regulatory T cells in human autoimmune diseases.
AB  - In the most simplistic terms, immune tolerance can be envisioned as a balance
      with autoreactive cells that arise naturally in all individuals on one side and
      regulatory mechanisms designed to counter those autoreactive processes on the
      other. A tilt of the balance toward the autoreactive side, either by increasing
      the number or function of autoreactive cells or by diminishing regulatory
      mechanisms, is manifested as autoimmunity. In contrast, tilting of the balance
      toward increased regulation could conceivably cause immunodeficiency. Regulatory
      T cells (T(REG)), and particularly the naturally arising CD4(+)CD25(+) subset of
      T(REG) cells, provide a substantial component of the autoimmune counterbalance.
      The identification of forkhead box P3 (FOXP3) as a critical determinant of
      CD4(+)CD25(+) T(REG) development and function has provided new opportunities and
      generated expanded interest in studying the delicate balance between autoimmunity
      and regulatory mechanisms in human autoimmune diseases. Identification of both
      human and mouse syndromes in which FOXP3 is mutated, and consequently
      CD4(+)CD25(+) T(REG) cells are absent, has led to a rapid accumulation of
      knowledge regarding T(REG) development and function over the past 5 years. The
      recent development of antibody reagents to specifically identify CD4(+)CD25(+)
      T(REG) cells by their FOXP3 expression has provided new tools to identify these
      elusive cells and investigate their role in human disease. This review will focus
      on the current state of knowledge regarding the role of T(REG) in human
      autoimmune diseases and on specific human immunodeficiencies that provide
      interesting models of autoimmunity.

PMID- 16902773
TI  - The cys-loop ligand-gated ion channel superfamily of the honeybee, Apis
      mellifera.
AB  - Members of the cys-loop ligand-gated ion channel (cys-loop LGIC) superfamily
      mediate neurotransmission in insects and are targets of successful insecticides.
      We have described the cys-loop LGIC superfamily of the honeybee, Apis mellifera,
      which is an important crop pollinator and a key model for social interaction. The
      honeybee superfamily consists of 21 genes, which is slightly smaller than that of
      Drosophila melanogaster comprising 23 genes. As with Drosophila, the honeybee
      possesses ion channels gated by acetylcholine, gamma-amino butyric acid,
      glutamate and histamine as well as orthologs of the Drosophila pH-sensitive
      chloride channel (pHCl), CG8916, CG12344 and CG6927. Similar to Drosophila,
      honeybee cys-loop LGIC diversity is broadened by differential splicing which may
      also serve to generate species-specific receptor isoforms. These findings on Apis
      mellifera enhance our understanding of cys-loop LGIC functional genomics and
      provide a useful basis for the development of improved insecticides that spare a
      major beneficial insect species.

PMID- 16902776
TI  - Functional differences between macaque prefrontal cortex and caudate nucleus
      during eye movements with and without reward.
AB  - The prefrontal cortex and the basal ganglia form mutually connected networks and
      are thought to play essential roles together in guiding goal-directed behaviors.
      Yet, these structures seem to have independent pathways to motor outputs as well,
      suggesting differential contributions to goal-directed behaviors. We hypothesized
      that the prefrontal cortex guides actions to a direction required by external
      demands and the basal ganglia guide actions to an internally motivated direction.
      To test this hypothesis, we used a task in which monkeys were required to make a
      memory-guided saccade to a direction indicated by a visual cue while only one
      direction was associated with reward. We observed a functional dissociation
      between the lateral prefrontal cortex (LPFC), which commonly represented the cue
      direction, and the caudate nucleus (CD), which commonly represented the reward
      associated direction. Furthermore, cue-directed and reward-directed signals were
      integrated differently in the two areas; when the cue direction and the reward
      direction were opposite, LPFC neurons maintained tuning to the cue direction,
      whereas CD neurons lost the tuning. Different types of spatial tuning in the two
      brain areas may contribute to different types of goal-directed behavior.

PMID- 16902778
TI  - [Update on rheuma-orthopedics - role and therapeutic options].
AB  - Orthopaedic treatment options for rheumatological patients have been further
      developed over recent years. For orthopaedic treatment, a range of different
      interventions are offered: orthoses and special technical aids as well as
      injections for joints and tendons, or surgery. Surgical interventions cover joint
      preservation, restitution and arthrodeses. Improvements in equipment and surgical
      procedures also make minimally invasive interactions possible for rheumatoid
      diseases. Thus, postoperative morbidity has been reduced significantly.
      Improvement in function, reduction of pain and prevention of recurrent local
      inflammation are primary. Considering these aims, arthrodeses are restricted to
      special indications. Joint preservation and restitution are the predominant
      measures used. The various procedures are discussed.

PMID- 16902779
TI  - The possible association of Chlamydia pneumoniae infection with nasal polyps.
AB  - The objective of this study was to investigate the possible etiologic role of
      Chlamydia pneumoniae infection in nasal polyps. This prospective clinical study
      was undertaken enrolling 30 patients with nasal polyps, and 30 age and sex
      matched control subjects from whom epithelial material was obtained during
      endoscopic surgery. IgG specific ELISA was used to determine seropositivity, and
      indirect immunoflorescence to determine C. pneumoniae in the biopsy material. C.
      pneumoniae specific IgG antibodies were found to be positive in 16 (53.3%) of the
      patients with nasal polyps, and 9 (22%) of the control subjects (P = 0.065).
      Indirect immunofluorescence results indicate that there was a significant
      difference between groups; 16 (53.3%) patients in the study group and 8 (26.6%)
      patients in the control group were found to be positive (P = 0.034). We found no
      correlation with cigarette smoking. Our results indicated that Chlamydia
      pneumoniae is possibly associated with the presence of nasal polyps. However,
      these results remain to be confirmed with further studies using other techniques,
      and the underlying mechanism should be defined.

PMID- 16902780
TI  - Injection tongueplasty: effects of sclerosant OK-432 on rat tongue.
AB  - Our aim was to investigate the effect of sclerosant agent OK-432 on tongue
      fibrosis and to determine whether the fibrosis formed by this substance increases
      with dose. Fifty Wistar albino rats were divided into three groups for the study.
      In the first group 0.2 ml OK-432, in the second group 0.5 ml OK-432, and in the
      third group physiological saline as the control substance was injected into the
      tongue of these rats. Subjects were sacrificed on the first day, first week,
      first month, third month and sixth month following the injection. Cross-sections
      of the tongues were stained with hematoxylin-eosin (HE) and Masson Tri-chrome.
      The degree of fibrosis was measured using ocular micrometry. A significant amount
      of fibrosis was observed in both the 0.2 ml (P = 0.020) and 0.5 ml (P = 0.003) OK
      432 injection groups. OK-432 is a material that causes significant fibrosis in
      the muscle when compared to physiological saline. The degree of fibrosis in the
      tongue increases with dose.

PMID- 16902782
TI  - Modified endoscopic swallowing test for improved diagnosis and prevention of
      aspiration.

PMID- 16902783
TI  - Renal function and cardiopulmonary bypass in pediatric cardiac surgical patients.
AB  - We studied prospectively the perioperative changes of renal function in nine
      children undergoing cardiac surgery with cardiopulmonary bypass (CPB). Glomerular
      filtration rate (GFR) and effective renal plasma flow (ERPF) were measured with
      inulin and (131)I-hippuran clearances before CPB, during hypo and normothermic
      CPB, following sternal closure and 1 h postoperatively. Urinary alpha glutathione
      S-transferase (alpha GS-T) was measured pre- and postoperatively as a marker for
      tubular cellular damage. Plasma and urine creatinine and electrolytes were
      measured. Free water, osmolal and creatinine clearances, as well as fractional
      excretion of sodium (FeNa) and potassium transtubular gradient (TTKG) were
      calculated. GFR was normal before and after surgery. ERPF was low before and
      after surgery; it increased significantly immediately after CPB. Filtration
      fraction (FF) was abnormally elevated before and after surgery; however, a
      significant decrease during normothermic CPB and sternal closure was found. Alpha
      GS-T presented a moderate, but nonsignificant increase postoperatively. FeNa also
      increased in this period, but not significantly. Creatinine, osmolal, free water
      clearances, as well as TTKG, were normal in all patients pre- and
      postoperatively. We conclude that there is no evidence of clinically significant
      deterioration of renal function in children undergoing repair of cardiac lesions
      under CPB. Minor increases of alpha GS-T in urine postoperatively did not confirm
      cellular tubular damage. There was no tubular dysfunction at that time.

PMID- 16902784
TI  - Mechanisms of development and progression of cyanotic nephropathy.
AB  - Cyanotic nephropathy (CN) is often accompanied by congenital cyanotic heart
      diseases (CCHD). The purpose of this study was to clarify the risk factors and
      the mechanisms of involved in the development and progression of CN. Thirty
      patients with CCHD were examined. We analyzed the risk factors for the
      development of CN on the basis of the clinical and laboratory findings. We also
      examined ten renal biopsy specimens obtained from patients with CN. Patients with
      CN showed significantly higher hematocrit levels than those without CN (P=0.025),
      although there was no difference between the two groups in terms of oxygen
      saturation. The renal plasma flow (RPF) in patients both with and without CN was
      low. However, the filtration fraction (FF) was significantly lower in patients
      with CN than in those without CN (P=0.001). The glomeruli of biopsy specimens
      with significant proteinuria (n=7) were larger than those of biopsy specimens
      without significant proteinuria, and there were more capillaries per glomerulus
      in the former than in the latter (n=3) and the control specimens (n=6)
      (glomerular size: P<0.01; number of glomerular capillaries: P<0.01). In
      conclusion, hyperviscosity by polycythemia may be responsible for the development
      of CN. This pathological condition may induce an angiogenic increase in the
      glomerular capillary beds, in turn leading to glomerulomegaly. In addition, the
      failure of a compensatory mechanism to respond to reduced RPF by hyperfiltration
      may be accompanied by the development and progression of CN.

PMID- 16902785
TI  - ACE inhibition can improve orthostatic proteinuria associated with nutcracker
      syndrome.
AB  - Left renal vein entrapment syndrome (nutcracker syndrome) was documented by
      magnetic resonance angiography (MRA) as a cause of orthostatic proteinuria in a
      14-year-old girl female adolescent. Because of continuous proteinuria we
      performed a left renal biopsy which showed moderate mesangial hypercellularity.
      Her overt orthostatic proteinuria disappeared after a treatment of angiotensin
      converting enzyme (ACE) inhibition. Nutcracker syndrome remains a rare but
      important cause of elevated protein excretion, which can induce mesangial changes
      and be improved by ACE inhibitor treatment.

PMID- 16902786
TI  - Treatment of the first episode of nephrotic syndrome in children.

PMID- 16902787
TI  - Ty3/gypsy-like retrotransposon knockout of a 2-methyl-6-phytyl-1,4-benzoquinone
      methyltransferase is non-lethal, uncovers a cryptic paralogous mutation, and
      produces novel tocopherol (vitamin E) profiles in sunflower.
AB  - The m (Tph(1)) mutation partially disrupts the synthesis of alpha-tocopherol
      (vitamin E) in sunflower (Helianthus annuus L.) seeds and was predicted to
      disrupt a methyltransferase activity necessary for the synthesis of alpha- and
      gamma-tocopherol. We identified and isolated two 2-methyl-6-phytyl-1,4
      benzoquinone/2-methyl-6-solanyl-1,4-benzoquinone methyltransferase (MPBQ/MSBQ-MT)
      paralogs from sunflower (MT-1 and MT-2), resequenced MT-1 and MT-2 alleles from
      wildtype (m(+) m(+)) and mutant (m m) inbred lines, identified m as a non-lethal
      knockout mutation of MT-1 caused by the insertion of a 5.2 kb Ty3/gypsy-like
      retrotransposon in exon 1, and uncovered a cryptic codominant mutation (d) in a
      wildtype x mutant F(2) population predicted to be segregating for the m mutation
      only. MT-1 and m cosegregated and mapped to linkage group 1 and MT-1 was not
      transcribed in mutant homozygotes (m m). The m locus was epistatic to the d locus
      -the d locus had no effect in m(+) m(+) and m(+) m individuals, but significantly
      increased beta-tocopherol percentages in m m individuals. MT-2 and d
      cosegregated, MT-2 alleles isolated from mutant homozygotes (d d) carried a 30 bp
      insertion at the start of the 5'-UTR, and MT-2 was more strongly transcribed in
      seeds and leaves of wildtype (d(+) d(+)) than mutant (d d) homozygotes
      (transcripts were 2.2- to 5.0-fold more abundant in the former than the latter).
      The double mutant (m m d d) was non-lethal and produced 24-45% alpha- and 55-74%
      beta-tocopherol (the wildtype produced 96% alpha- and 4% beta-tocopherol). MT-2
      compensated for the loss of the MT-1 function, and the MT-2 mutation profoundly
      affected the synthesis of tocopherols without adversely affecting the synthesis
      of plastoquinone crucial for normal plant growth and development.

PMID- 16902788
TI  - Different states of energy metabolism in the vertebrate retina can be identified
      by stimulus-related changes in near UV transmission.
AB  - BACKGROUND: Our aim was to identify different states of energy metabolism in the
      perfused isolated vertebrate retina by simultaneous recordings of light-evoked
      changes of transretinal potential (TRP) and spectroscopic changes related to
      oxidation of pyridine nucleotides. METHODS: Isolated retinas were obtained from
      R.esc. and superfused. For each setting, three experiments were performed.
      Eighteen retinas were used. TRP as a response to light stimulation was recorded
      simultaneously with stimulus-induced transmission shift at 350 nm. These
      responses were recorded under normal conditions, under withdrawal of oxygen and
      glucose, and after addition of electron transport inhibitors and uncouplers of
      oxidative phosphorylation. RESULTS: Under normal conditions, TRP was strongly
      correlated with transmission shift after light stimulation. Without oxygen,
      amplitudes of stimulus-related TRP decreased and response related increase of
      transmission at 350 nm was reduced. The retina showed a much higher general
      absorption of the analyzing light. During glucose lack, an overall increase in
      transmission at 350 nm could be observed. The addition of Amytal yielded a
      specific reduction of the OFF components. Cyanide attenuated the ON and OFF
      components. Dinitrophenol yielded a considerable loss of the electrical ON
      response. Transmission change was affected less than electrical signal.
      Chlorophenylhydrazine induced a reproducible reduction of electrical responses,
      with a relative increase of transmission shift at 350 nm. CONCLUSION: In the
      isolated perfused retina, different states of energy metabolism and their
      specific impact on neuroretinal responses can be examined by simultaneous
      recordings of stimulus-related neuronal activity and spectroscopic changes.

PMID- 16902789
TI  - [A look beyond urology: vaginal cancer].
AB  - Primary carcinomas of the vagina are very rare. Nevertheless, they need to be
      included in differential diagnoses when carrying out a urological examination of
      the pelvic floor and the vagina in patients with micturition problems, also in
      younger patients: we report a case of a 35-year-old woman with a primary
      carcinoma of the vagina and present a review of the literature.

PMID- 16902790
TI  - [The German Society of Urology in 2006. Well equipped for the challenges of the
      time].

PMID- 16902792
TI  - Efficacy of methylprednisolone in controlling complications after impacted lower
      third molar surgical extraction.
AB  - INTRODUCTION: Impacted third molar extraction causes considerable swelling in the
      days immediately following surgery. The aim of the present investigation was to
      evaluate the efficacy of methylprednisolone as a single 40-mg intramuscular dose
      in controlling the complications of impacted lower third molar surgical removal.
      MATERIALS AND METHODS: Thirty-five patients were evaluated within the framework
      of a consecutive sampling and double-blind study with intrasubject measurements.
      Extraction comprised ostectomy with tooth sectioning of both lower third molars
      under local anesthesia. The study group received 40 mg of methylprednisolone
      injected into the gluteal region, while the controls received no such medication.
      In each individual one molar was randomly assigned to the study group and the
      other to the control series - with extraction of the two teeth being spaced 1
      month apart. Evaluations were made of postoperative pain, trismus and swelling,
      and measurements were obtained for oral aperture and various distances (tragus
      lip commissure, gonion-lip commissure and gonion-external canthus of the eye)
      before surgery and 2-7 days after extraction. Statistical correlations were made
      based on the Student t-test for the comparison of means of related samples.
      RESULTS: A statistically and clinically significant association was observed 2
      days after surgery between methylprednisolone administration and increased oral
      aperture and diminished facial swelling. Likewise, less pain was recorded in the
      study group 6 h after surgery. CONCLUSION: The results confirm the efficacy of
      methylprednisolone in providing a more comfortable postoperative course after
      surgical extraction of impacted lower third molars.

PMID- 16902793
TI  - Block by internal Mg2+ causes voltage-dependent inactivation of Kv1.5.
AB  - Internal Mg2+ blocks many potassium channels including Kv1.5. Here, we show that
      internal Mg2+ block of Kv1.5 induces voltage-dependent current decay at strongly
      depolarised potentials that contains a component due to acceleration of C-type
      inactivation after pore block. The voltage-dependent current decay was fitted to
      a bi-exponential function (tau(fast) and tau(slow)). Without Mg2+, tau(fast) and
      tau(slow) were voltage-independent, but with 10 mM Mg2+, tau(fast) decreased from
      156 ms at +40 mV to 5 ms at +140 mV and tau(slow) decreased from 2.3 s to 206 ms.
      With Mg2+, tail currents after short pulses that allowed only the fast phase of
      decay showed a rising phase that reflected voltage-dependent unbinding. This
      suggested that the fast phase of voltage-dependent current decay was due to Mg2+
      pore block. In contrast, tail currents after longer pulses that allowed the slow
      phase of decay were reduced to almost zero suggesting that the slow phase was due
      to channel inactivation. Consistent with this, the mutation R487V (equivalent to
      T449V in Shaker) or increasing external K+, both of which reduce C-type
      inactivation, prevented the slow phase of decay. These results are consistent
      with voltage-dependent open-channel block of Kv1.5 by internal Mg2+ that
      subsequently induces C-type inactivation by restricting K+ filling of the
      selectivity filter from the internal solution.

PMID- 16902794
TI  - Determinants of myocardial blood flow response to cold pressor testing and
      pharmacologic vasodilation in healthy humans.
AB  - PURPOSE: Response of myocardial blood flow (MBF) to sympathetic stimulation with
      cold is modulated by endothelium-related factors and is typically altered in the
      presence of coronary risk factors. Determinants of flow response to cold pressor
      testing (CPT) in normal volunteers at low risk for CAD remain less well defined,
      especially relative to baseline conditions such as hemodynamics and MBF, plasma
      substrate and lipid levels, and total pharmacologically stimulated vasodilator
      capacity. METHODS: In 50 normal volunteers (42+/-13 years; 31 women) without
      coronary risk factors, insulin resistance, or family history of
      diabetes/premature CAD, MBF was measured with (13)N-ammonia and PET at baseline,
      during CPT, and during pharmacologic hyperemia. RESULTS: Sympathetic stimulation
      with CPT raised heart rate and blood pressure and thus MBF (Delta MBF=0.23+/-0.09
      ml/min/g). MBF response, defined in absolute flow units as the difference between
      CPT and baseline, was independent of age, gender, heart rate, and blood pressure
      and rate-pressure product (RPP) at baseline as well as plasma substrate and lipid
      levels with the exception of an association with HDL cholesterol (rho=0.40,
      p=0.005) but depended on the change in RPP from rest (rho=0.33, p=0.019).
      Finally, changes in coronary vascular resistance in response to CPT were
      associated with changes in pharmacologic vasodilation (rho=0.56, p<0.0001).
      CONCLUSION: MBF response to sympathetic stimulation with cold (NO-mediated
      endothelium-dependent vasomotion), reflecting the functional state of the
      coronary endothelium, was independent of gender, age, and resting heart
      conditions. It was modulated by HDL cholesterol levels, even in healthy
      volunteers, and also related to pharmacologically stimulated vasodilator capacity
      at the coronary vascular resistance level.

PMID- 16902795
TI  - Genetic comparison of liver flukes, Clonorchis sinensis and Opisthorchis
      viverrini, based on rDNA and mtDNA gene sequences.
AB  - To clarify the genetic relationships between Clonorchis sinensis and Opisthorchis
      viverrini, patterns of inter-/intraspecific polymorphism were compared for four
      markers with nuclear ribosomal DNA (rDNA) and mitochondrial DNA (mtDNA) in liver
      flukes C. sinensis from Korea (Kimhae) and China (Shenyang and Nanning) and O.
      viverrini from Laos (Savannakhet). Intra- and interspecific variations in the
      18S, ITS2, and 28S rDNA and mitochondrial cytochrome c oxidase subunit I (mtCOI)
      of mtDNA gene sequences were low and nearly identical. Three isolates of C.
      sinensis showed a high similarity (99-100%). No variation was detectable in the
      ITS2 sequence for the C. sinensis from Korea and China. ITS2 region sequences of
      O. viverrini vs C. sinensis showed 95% identity and differed at 28 nucleotide
      positions. Pairwise sequence divergence with three C. sinensis isolates and O.
      viverrini ranged from 0 to 3.94% in mtCOI gene. The mtCOI sequences were more
      highly conserved relative to the ITS2 sequences. These genetic data from
      different geographical areas showed that the liver flukes are not variable and
      are virtually identical almost despite belonging to entirely different genera.

PMID- 16902797
TI  - CIMT meets strategies for immune therapy. Report and abstracts of the 4th
      International Meeting of the Association for Immunotherapy of Cancer, Mainz,
      Germany, 4-5 May 2006.

PMID- 16902796
TI  - Intramyocellular lipid stores increase markedly in athletes after 1.5 days lipid
      supplementation and are utilized during exercise in proportion to their content.
AB  - Intramyocellular lipids (IMCL) and muscle glycogen provide local energy during
      exercise (EX). The objective of this study was to clarify the role of high versus
      low IMCL levels at equal initial muscle glycogen on fuel selection during EX.
      After 3 h of depleting exercise, 11 endurance-trained males consumed in a
      crossover design a high-carbohydrate (7 g kg(-1) day(-1)) low-fat (0.5 g kg(-1)
      day(-1)) diet (HC) for 2.5 days or the same diet with 3 g kg(-1) day(-1) more fat
      provided during the last 1.5 days of diet (four meals; HCF). Respiratory
      exchange, thigh muscle substrate breakdown by magnetic resonance spectroscopy,
      and plasma FFA oxidation ([1-(13)C]palmitate) were measured during EX (3 h, 50% W
      (max)). Pre-EX IMCL concentrations were 55% higher after HCF. IMCL utilization
      during EX in HCF was threefold greater compared with HC (P < 0.001) and was
      correlated with aerobic power and highly correlated (P < 0.001) with initial
      content. Glycogen values and decrements during EX were similar. Whole-body fat
      oxidation (Fat(ox)) was similar overall and plasma FFA oxidation smaller (P <
      0.05) during the first EX hour after HCF. Myocellular fuels contributed 8% more
      to whole-body energy demands after HCF (P < 0.05) due to IMCL breakdown (27%
      Fat(ox)). After EX, when both IMCL and glycogen concentrations were again similar
      across trials, a simulated 20-km time-trial showed no difference in performance
      between diets. In conclusion, IMCL concentrations can be increased during a
      glycogen loading diet by consuming additional fat for the last 1.5 days. During
      subsequent exercise, IMCL decrease in proportion to their initial content, partly
      in exchange for peripheral fatty acids.

PMID- 16902798
TI  - Unfertilized ovary: a novel explant for coconut (Cocos nucifera L.) somatic
      embryogenesis.
AB  - Unfertilized ovaries isolated from immature female flowers of coconut (Cocos
      nucifera L.) were tested as a source of explants for callogenesis and somatic
      embryogenesis. The correct developmental stage of ovary explants and suitable in
      vitro culture conditions for consistent callus production were identified. The
      concentration of 2,4-dichlorophenoxyacetic acid (2,4-D) and activated charcoal
      was found to be critical for callogenesis. When cultured in a medium containing
      100 microM 2,4-D and 0.1% activated charcoal, ovary explants gave rise to 41%
      callusing. Embryogenic calli were sub-cultured into somatic embryogenesis
      induction medium containing 5 microM abscisic acid, followed by plant
      regeneration medium (with 5 microM 6-benzylaminopurine). Many of the somatic
      embryos formed were complete with shoot and root poles and upon germination they
      gave rise to normal shoots. However, some abnormal developments were also
      observed. Flow cytometric analysis revealed that all the calli tested were
      diploid. Through histological studies, it was possible to study the sequence of
      the events that take place during somatic embryogenesis including orientation,
      polarization and elongation of the embryos.

PMID- 16902799
TI  - New role of the trigeminal nerve as a neuronal pathway signaling brain in acute
      periodontitis: participation of local prostaglandins.
AB  - The systemic induction of cytokines and prostaglandins plays a key role in the
      development of fever. However, whether fever is triggered by local injection of
      lipopolysaccharide (LPS) and the involvement of locally produced prostaglandins
      in periodontal tissue has never been assessed. Thus, we tested the hypothesis
      that the trigeminal nerve is a neuronal pathway that signals the brain during
      acute periodontitis, and this response involves prostaglandin induction. Rats
      were given a gingival intra-pouch injection of sterile saline or Escherichia coli
      lipopolysaccharide, at doses of 10 and 100 microg/kg. Some animals were pre
      treated with the local anesthetic mepivacaine or had the peripheral branches of
      the trigeminal nerves transected. Another group of animals were pre-treated
      (locally or systemically) with the nonselective inhibitor of cyclooxygenases
      diclofenac. Body core temperature (T (b)) was measured by means of biotelemetry
      before and after injections. LPS elicited a dose-dependent increase in T (b),
      which was abolished by mepivacaine, bilateral transection of the peripheral
      branches of the trigeminal nerve, or local treatment with diclofenac. The results
      indicate that there is an activation of periodontal nerves to induce fever by
      LPS. It also shows that local formation of prostaglandins plays a role in fever
      development. Moreover, immunohistochemistry detected c-fos expression in the
      subnucleus caudalis of spinal trigeminal nucleus and in the preoptic area of the
      hypothalamus 2 and 3 h after LPS injection, further confirming the role of
      trigeminal nerve signaling brain in acute periodontitis.

PMID- 16902800
TI  - A practical method for assessment of dose conversion coefficients for aquatic
      biota.
AB  - Radiological impact assessment for flora and fauna requires adequate dosimetric
      data. Due to the variability of habitats, shapes, and masses of the non-human
      biota, assessment of doses is a challenging task. External and internal dose
      conversion coefficients for photons and electrons have been systematically
      calculated by Monte Carlo methods for spherical and ellipsoidal shapes in water
      medium. An interpolation method has been developed to approximate absorbed
      fractions for elliptical shape organisms from absorbed fractions for spherical
      shapes with reasonable accuracy. The method allows an evaluation of dose
      conversion coefficients for arbitrary ellipsoids for photon and electron sources
      with energies from 10 keV to 5 MeV, and for organism masses in the range from 10(
      6) to 10(3) kg. As an example of the application of the method, a set of dose
      coefficients for aquatic organisms discussed as reference animals and plants in a
      draft of an up-coming publication of the International Commission on Radiological
      Protection has been determined.

PMID- 16902801
TI  - [The consequences of stroke for the artist Lovis Corinth].
AB  - The artist Lovis Corinth suffered a right-hemispheric stroke at the age of 53
      years but only died 14 years later. The huge amount of work he produced after
      this life threatening disease allows detailed analysis of his post-stroke artwork
      in comparison to pre-stroke. When performing this analysis as a neurologist, an
      enormous diversity of subtle stroke sequelae can be discovered that are mostly
      explained by left-sided hemi-neglect. These findings clearly go far beyond pure
      psychological processes. Moreover, Corinth is a motivating example for disabled
      patients because he was able to produce great artwork after his stroke. He was
      struggling against a motor disability admittedly not severely affecting his
      artistic production, but also against severe neuropsychological deficits that did
      have clear consequences. Lovis Corinth left us the credo "True art means to use
      unreality". Taken together with the often cited phrase "Drawing means to leave
      out (details)", a clear-cut interpretation for neurologists can be derived from
      the understanding of right-hemisphere lesions and subsequent left-sided neglect.

PMID- 16902802
TI  - Tissue distribution and excretion of myosmine after i.v. administration to Long
      Evans rats using quantitative whole-body autoradiography.
AB  - Occurrence of the tobacco alkaloid myosmine has been proven in various staple
      foods, vegetables and fruits. Myosmine can be easily activated by nitrosation
      yielding 4-hydroxy-1-(3-pyridyl)-butanone (HPB) and the esophageal carcinogen N'
      nitrosonornicotine. Most of the reaction products after myosmine peroxidation
      were also identified as urinary metabolites after oral administration to rats.
      Whole-body autoradiography with freeze dried or multiple solvent extracted tissue
      sections was used to trace [2'-(14)C]myosmine (0.1 mCi/kg bw) 0.1, 0.25, 1, 4 and
      24 h after i.v. injection in Long-Evans rats. In addition, in vitro binding of
      radioactivity to esophageal and eye tissue was determined and excretion of
      radioactivity via urine and feces was quantified. Radioactivity is rapidly
      eliminated by renal excretion. Approximately 30% of the administered
      radioactivity was recovered in urine within the first 4 h and excretion with
      urine (72%) and feces (15%) was nearly complete after 24 h. A rapid concentration
      of radioactivity can be seen in the stomach and in the salivary and lachrymal
      glands. Rats killed 1 and 4 h after treatment showed by far the highest labeling
      in the accessory genital gland. High levels of nonextractable radioactivity were
      present in esophageal tissue and melanin. The half lives for the disappearance of
      radioactivity from various tissues are in the order of about 1 h. Eye and
      esophagus sections both showed nonextractable labeling after in vitro incubation
      with (14)C-myosmine. In conclusion, the toxicological significance of myosmine
      accumulation in esophagus and accessory genital gland requires further
      investigations. Hair analysis might be applicable for myosmine biomonitoring,
      because of possible enrichment in melanin containing tissues.

PMID- 16902803
TI  - Hepatotoxin-induced hypertyrosinemia and its toxicological significance.
AB  - A (1)H Nuclear Magnetic Resonance (NMR) spectroscopic investigation of the
      effects of single doses of four model hepatotoxins on male Sprague-Dawley rats
      showed that hypertyrosinemia was induced by three of the treatments (ethionine
      300 mg/kg, galactosamine hydrochloride 800 mg/kg and isoniazid 400 mg/kg) but not
      by the fourth (thioacetamide 200 mg/kg). Concomitant histopathological and
      clinical chemistry analyses showed that hypertyrosinemia could occur with or
      without substantial hepatic damage and that substantial hepatic damage could
      occur without hypertyrosinemia. However, in the rats dosed with galactosamine
      hydrochloride, which showed highly variable amounts of liver damage at ca. 24 h
      after dosing, a clear relationship was found between the degree of
      hypertyrosinemia and the extent of the hepatic necrosis induced. In line with the
      cause of clinically observed Type II Tyrosinemia, we consider that the critical
      event in the onset of hepatotoxin-induced hypertyrosinemia is likely to be a
      reduction in hepatic tyrosine aminotransferase (TAT) activity. We discuss
      mechanisms by which TAT activity could be lost with special consideration given
      to pyridoxal 5'-phosphate (P5P) depletion and to the inhibition of protein
      synthesis. This analysis may have implications for the interpretation of clinical
      measures of liver status such as Fischer's ratio and the branched-chain tyrosine
      ratio (BTR).

PMID- 16902805
TI  - [Raynaud phenomenon in dermatology. Part 1: Pathophysiology and diagnostic
      approach].
AB  - Raynaud phenomenon (RP) is characterized by recurrent spasms of small digital
      arterioles/arteries at fingers and toes, usually triggered by cold and emotional
      stress. Clinically a sudden pallor of individual digits is followed by reactive
      hyperemia, in severe cases also by cyanosis. One distinguishes between primary
      RP, i.e. RP without an underlying disease or drug intake, and secondary RP, which
      is causally related to an underlying disease or to intake of certain drugs (e.g.
      interferon, cisplatin). Primary RP is frequent (prevalence of about 13-20% in
      northern or central Europe), while secondary RP is rare, but the major presenting
      symptom for systemic sclerosis (SSc). Differential diagnosis includes cold
      induced pallor, acute embolic events, paroxysmal hematoma of the finger or
      erythromelalgia. Vasoconstrictive mechanisms outweigh vasodilatory ones in
      endothelial cells and vascular smooth muscle. Although soluble mediators such as
      endothelin or certain prostaglandins have been exploited successfully for
      therapy, the extent of their involvement in the initial pathophysiology of RP is
      unclear. Secondary RP (associated with SSc) additionally features morphological
      alterations with compromise of the vessel lumen. As RP can result in severe
      discomfort and complications, timely diagnosis and treatment is essential.

PMID- 16902804
TI  - Alterations in health examination items and skin symptoms from exposure to ultra
      low humidity.
AB  - OBJECTIVES: Several lines of evidence have shown that insufficient humidity could
      result in health problems but no studies have been performed in ultra-low
      humidity (ULH) environments. The aims of this study are to investigate the health
      examination items alterations and skin symptoms of workers exposed to ULH
      environment based on a longitudinal study design. METHODS: Twelve male ULH (RH =
      1.5%) workers and 12 age-sex-matched reference workers were selected. The
      examination items in blood and urine as well as the skin problems were compared
      between ULH workers and controls, and between ULH workers in 2000 and 2003.
      Biochemistry analysis of blood and urine were implemented from annual health
      examinations. Information on skin symptoms and diseases were obtained from a
      structured questionnaire in 2000 and 2003. RESULTS: The alterations in mean
      corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin
      concentration, and total cholesterol in blood analysis and only sediment-WBC in
      urine analysis were found significantly different in 2000. These changes were
      almost fully recovered in 2003 although a consistently significant elevation in
      the urine specific gravity was found during the 3-year follow-up period. Skin
      disorders, however, showed an earlier elevated itching symptom in lower limb and
      pretibial that developed to physician-diagnosed contact dermatitis. CONCLUSIONS:
      Long-term ULH exposure could cause progressive pathological changes in the skin
      and urine concentration elevation. Because low humidity condition occurs
      frequently in air-conditioned buildings, the findings of this study suggest the
      population long-term exposed to low humidity should be cautious about health
      manifestations living in a low humidity environment. While the indoor environment
      is equipped with an air-conditioner, continuous monitoring on the humidity is
      recommended.

PMID- 16902806
TI  - [Uveitis and the aging].
AB  - Uveitis can be found in all age groups, but the age of disease onset may provide
      important information on the etiology of the disease. New data on the
      epidemiology of uveitis disclose a higher incidence and prevalence in older
      patients then has previously been found. Masquerade syndromes which mimic uveitis
      may be found especially in younger and older patients. These have to be excluded
      from regular intraocular inflammation. Here, intraocular lymphoma plays a major
      role which is most often associated with severe clinical, diagnostic and
      therapeutic challenges. One of the major complications of uveitis is cataract
      formation. Keeping in mind the importance of pre- and postoperative treatment,
      even implantation of an intraocular lens in older patients with uveitis is
      currently a safe procedure.

PMID- 16902807
TI  - A novel technique for vas deferens transection repairs.
AB  - The purpose of this study is to describe a technique, that is as successful as
      microsurgery in terms of patency rates and histopathologic assessments, and can
      be performed even by untrained hands in microsurgery, for repairing vas deferens
      injuries that can be perceived during inguinal herniorrhaphy. Thirty male Wistar
      Albino rats were randomly allocated to five groups. In control group, the vas
      deferens was harvested without any surgical intervention (Group 1) and in sham
      group the vas was harvested after a limited dissection (Group 2). Three suture
      approximation technique was carried out in Group 3, and a novel vasovasostomy
      technique was carried out by using a hypodermal needle in Groups 4 and 5, with
      polypropylene and polyglactin 910 (rapid vicryl), respectively. Results were
      evaluated in terms of operative time, patency and flow rates, inflammation and
      sperm granuloma. The mean operative times for hypodermal needle assisted
      approximation of Groups 4 and 5 were found significantly less than Group 3. The
      compared results of the groups in terms of patency, flow rate, inflammation and
      spermatic granuloma indicated Group 4 to be superior to the other groups. We have
      found the hypodermal needle assisted approximation technique to be easier, less
      time consuming and cost effective. With these promising results, this modus
      operandi can be described as an appropriate technique for vas deferens
      transection repairs.

PMID- 16902808
TI  - Pre-exposure to a novel nutritional mixture containing a series of phytochemicals
      prevents acetaminophen-induced programmed and unprogrammed cell deaths by
      enhancing BCL-XL expression and minimizing oxidative stress in the liver.
AB  - From a disease-prevention perspective, recent progress in phytochemical and
      nutraceutical research clearly suggests (benefits outweigh the risk pattern).
      Although powerful antioxidant properties have been the most acclaimed mechanism
      of action for these entities, the individual antioxidants studied in clinical
      trials do not appear to have consistent preventative effects. The actions of the
      antioxidant nutrients alone do not explain the observed health benefits of diets
      rich in fruits and vegetables for chronic diseases. Therefore, we proposed that
      the additive and synergistic effects of phytochemicals in fruits and vegetables
      are responsible for these potent antioxidant and anticancer activities, and that
      the benefit of a diet rich in fruits and vegetables is attributed to the complex
      mixture of phytochemicals present in plants [1]. Surprisingly, however, no
      studies have attempted to evaluate the combined antitoxic potential of a
      phytochemical-nutraceutical mixture (PNM) in in vivo models. Therefore, this
      study, for the first time, was designed to investigate whether pre-exposure to a
      unique PNM has the ability to impede mechanistic events involved in acetaminophen
      (APAP)-induced hepatotoxicity. Besides several vitamins and minerals in balanced
      proportions (approximately US RDA), the PNM used in this investigation contained
      several well-known phytochemicals such as citrus flavonoids, red wine
      polyphenols, Garcinia, Gymnema, Ginkgo, Ephedra sinica, Camellia sinensis,
      Silybum, Guarana, Eluthero, Allium sativum and Ocimum basilicum extracts. To
      evaluate PNM's antitoxic potential, groups of animals ICR mice, 3 months old)
      received either a control diet or PNM containing diets (1X and 10X) for 4 weeks.
      On day-28, animals were divided into two subgroups. Half the animals were
      administered normal saline and the other half received 400mg/kg ip injections of
      APAP. All the animals were sacrificed 24h after APAP exposure. Serum and tissue
      (liver and kidneys) samples were analyzed. APAP alone caused massive liver injury
      (nearly 495-fold increase in ALT) and oxidative stress (Lipid peroxidation: 268%
      increase in MDA) coupled with genomic DNA fragmentation (288% increase). Exposure
      to 1X-PNM for 28 days significantly reduced animal mortality and all the APAP
      induced biochemical events (In 1X-PNM + AP: ALT leakage decreased to 54 fold; MDA
      accumulation decreased to 125%, and DNA fragmentation decreased to 122%), whereas
      10X-PNM + APAP slightly escalated both oxidative stress and genomic DNA
      fragmentation preceding liver injury. Liver homogenates subjected to western blot
      analysis disclosed the ability of 1X-PNM to counteract APAP-induced decrease in
      Bcl-xL expression. Histopathological evaluation of stained liver tissue sections
      indicated anti-apoptogenic and anti-necrogenic reponses coupled with near
      complete prevention of glycogen depletion by 1X-PNM. Collectively, our
      investigation suggests that a mixture containing an assortment of
      phytochemicals/nutraceuticals may serve as a much more powerful blend in
      preventing drug or chemical-induced organ injuries than a single phytochemical or
      nutraceutical entity. In addition, ephedra and caffeine containing PNM-exposure
      in a controlled manner may potentially shield vital target organs from toxicities
      caused by intentional, unintentional or accidental exposures to structurally and
      functionally diverse drug and chemical entities.

PMID- 16902809
TI  - The effects of light and moderate-heavy ethanol exposure on the development of
      cirrhosis in rats.
AB  - Daily, light ethanol consumption has beneficial effects on liver recovery
      following partial hepatectomy and acute liver failure in rats. The aim of the
      present study was to determine whether such consumption has a beneficial,
      deleterious, or no effect on the progression of chronic hepatitis to cirrhosis in
      rats. Adult, male, Sprague-Dawley rats (n = 66) were gavaged with light (1.0
      g/kg/day) or moderate-heavy (3.0 g/kg) ethanol in water daily for the final 8
      weeks of a 10-week period of thioacetamide-induced cirrhosis. Control rats were
      gavaged with water alone. Compared to results in water-fed controls, light
      ethanol exposure had beneficial or no effects, while moderate-heavy ethanol
      exposure had deleterious effects on hepatic inflammation, function, regenerative
      activity, and fibrosis. The results of this study indicate that daily, light
      ethanol exposure does not have a deleterious effect on the progression of chronic
      liver disease to cirrhosis in this animal model.

PMID- 16902812
TI  - Rape shield laws and sexual behavior evidence: effects of consent level and
      women's sexual history on rape allegations.
AB  - Rape shield laws, which limit the introduction of sexual history evidence in rape
      trials, challenge the view that women with extensive sexual histories more
      frequently fabricate charges of rape than other women. The present study examined
      the relationship between women's actual sexual history and their reporting rape
      in hypothetical scenarios. Female participants (college students and a community
      sample, which included women working as prostitutes and topless dancers, and
      women living in a drug and alcohol rehabilitation center) imagined themselves in
      dating scenarios that described either a legally definable act of rape or
      consensual sexual intercourse. Additionally, within the rape scenarios, level of
      consensual intimate contact (i.e., foreplay) preceding rape was examined to
      determine its influence on rape reporting. Women were less likely to say that
      they would take legal action in response to the rape scenarios if they had
      extensive sexual histories, or if they had consented to an extensive amount of
      intimate contact before the rape. In response to the consensual sexual
      intercourse scenarios, women with more extensive sexual histories were not more
      likely to say that they would report rape, even when the scenario provided them
      with a motive for seeking revenge against their dating partner.

PMID- 16902810
TI  - Clinical response is associated with elevated plasma interleukin-1 receptor
      antagonist during selective granulocyte and monocyte apheresis in patients with
      ulcerative colitis.
AB  - Depletion of granulocytes and monocytes (GM) by selective apheresis (GMA) with an
      Adacolumn exerts an anti-inflammatory effect in patients with ulcerative colitis
      (UC) or rheumatoid arthritis. However, the mechanism of the anti-inflammatory
      effect of GMA is not fully understood yet. We investigated the effect of GMA on
      the plasma concentration of interleukin-1 receptor antagonist (IL-1ra), a potent
      anti-inflammatory cytokine. Twenty-six patients with active UC received GMA at
      one session per week for 5 consecutive weeks. Clinical response was defined as
      Deltaclinical activity index (DeltaCAI=CAI at entry - CAI at post)>or=4, while
      clinical remission was defined as CAI<or=4. Twenty-one of twenty-six patients
      (80.8%) responded to GMA. In the first session, plasma from responder patients
      showed a significant (P < 0.01) increase in IL-1ra in the Adacolumn outflow. In
      contrast, there was no change in IL-1ra in nonresponders. In conclusion, release
      of IL-1ra during GMA might be one mechanism of clinical efficacy associated with
      this therapy.

PMID- 16902813
TI  - Inhalation delivery and anti-tumor activity of celecoxib in human orthotopic non
      small cell lung cancer xenograft model.
AB  - PURPOSE: To determine the in vivo anti-tumor effect of aerosolized Celecoxib
      (Cxb) in combination with i.v Docetaxel (Doc) and compare the anti-tumor effect
      with oral Cxb combined with i.v Doc in human orthotopic non-small cell lung
      cancer (NSCLC) xenograft model. MATERIALS AND METHODS: Female Nu/Nu mice were
      implanted with orthotopic tumors by injecting A549 cells into the lung
      parenchyma. Seven day after tumor implantation the mice were treated with
      aerosolized Cxb (30 min exposure/day, 5 mg/ml solution) + i.v Doc (10 mg/kg) and
      the effect was compared with oral Cxb (150 mg/kg/day) + i.v Doc (10 mg/kg), for
      28 days. Small-animal nose only inhalation chamber (CH Technologies, Westwood,
      NJ) was utilized for aerosol exposure. Therapeutic activity of Cxb (aerosol/oral)
      + Doc was estimated by differences in lung weight, tumor area and animal body
      weight. Lung tumor samples isolated from mice were analyzed for (a) PGE2 levels
      by enzyme immunoassay (EIA) (b) expression of Fas and Factor VIII by
      immunohistochemistry (c) IL-8 expression using EIA kits and (d) mRNA expression
      for caspase-3 by Real-Time PCR. RESULTS: Mice treated with Cxb (aerosol/oral) +
      Doc showed significant reduction (P < 0.001) in lung weight and tumor area as
      compared to Cxb or Doc treatments. Cxb (aerosol/oral) + Doc showed increased
      apoptosis mediated via increased Fas and caspase-3 (P < 0.001) expression as
      compared to untreated control. Further, the combination treatment showed
      antiangiogenic effect as demonstrated by reduced expression of Factor VIII, IL-8
      (P < 0.001) and PGE2 (P < 0.001) in lung tumors as compared to untreated control.
      Aerosolized Cxb at a significantly lower therapeutic dose (4.56 mg/kg/day)
      demonstrated comparable anti-tumor efficacy to orally administered Cxb (150
      mg/kg/day). CONCLUSION: Cxb was formulated and effectively delivered via
      aerosolization to treat orthotopic lung tumors in combination with i.v Doc. Cxb
      when administered by aerosol produced same therapeutic effect as oral Cxb, but at
      lower therapeutic dose and thus shows promise for the treatment of lung cancer.

PMID- 16902814
TI  - Use of a dynamic in vitro lipolysis model to rationalize oral formulation
      development for poor water soluble drugs: correlation with in vivo data and the
      relationship to intra-enterocyte processes in rats.
AB  - PURPOSE: To examine the correlation between the in vitro solubilization process
      of lipophilic compounds from different lipid solutions and the corresponding in
      vivo oral bioavailability data. In particular, to assess the influence of intra
      enterocyte processes (metabolism and lymphatic absorption) on this correlation.
      MATERIALS AND METHODS: The dissolution of progesterone and vitamin D3 in long
      (LCT), medium (MCT) and short (SCT) chain triglyceride solutions were tested in a
      dynamic in vitro lipolysis model. The absolute oral bioavailability of the drugs
      from the tested formulations was investigated in rats. Vitamin D3 bioavailability
      was also examined following lymphatic transport blockage induced by cycloheximide
      (3 mg/kg). RESULTS: The dynamic in vitro lipolysis experiments indicated a rank
      order of MCT > LCT > SCT for both progesterone and vitamin D3. The
      bioavailability of progesterone correlated with the in vitro data, despite its
      significant pre-systemic metabolism. For vitamin D3, an in vivo performance rank
      order of LCT > MCT > SCT was obtained. However, when the lymphatic transport was
      blocked the bioavailability of vitamin D3 correlated with in vitro data.
      CONCLUSIONS: The in vitro lipolysis model is useful for optimization of oral
      lipid formulations even in the case of pre-systemic metabolism in the gut.
      However, when lymphatic transport is a significant route of absorption, the in
      vitro lipolysis data may not be predictive for actual in vivo absorption.

PMID- 16902816
TI  - Gender development in women with congenital adrenal hyperplasia as a function of
      disorder severity.
AB  - Prenatal-onset classical congenital adrenal hyperplasia (CAH) in 46,XX
      individuals is associated with variable masculinization/defeminization of the
      genitalia and of behavior, presumably both due to excess prenatal androgen
      production. The purpose of the current study was threefold: (1) to extend the
      gender-behavioral investigation to the mildest subtype of 46,XX CAH, the non
      classical (NC) variant, (2) to replicate previous findings on moderate and severe
      variants of 46,XX CAH using a battery of diversely constructed assessment
      instruments, and (3) to evaluate the utility of the chosen assessment instruments
      for this area of work. We studied 63 women with classical CAH (42 with the salt
      wasting [SW] and 21 with the simple virilizing [SV] variant), 82 women with the
      NC variant, and 24 related non-CAH sisters and female cousins as controls (COS).
      NC women showed a few signs of gender shifts in the expected direction, SV women
      were intermediate, and SW women most severely affected. In terms of gender
      identity, two SW women were gender-dysphoric, and a third had changed to male in
      adulthood. All others identified as women. We conclude that behavioral
      masculinization/defeminization is pronounced in SW-CAH women, slight but still
      clearly demonstrable in SV women, and probable, but still in need of replication
      in NC women. There continues a need for improved instruments for gender
      assessment.

PMID- 16902815
TI  - Effects of sodium taurocholate on the absorption of inhaled 99mTc-DTPA.
AB  - PURPOSE: The effects of a natural surface-active agent, sodium taurocholate
      (NaTC), on the absorption of a hydrophilic solute, technetium-99m-labelled
      diethylene triamine pentaacetic acid (99mTc-DTPA), deposited at various sites
      within the airways were evaluated in this open, cross-over, and single-dose
      study. METHODS: Nine healthy non-smokers received 99mTc-DTPA with or without the
      addition of NaTC, administered as an oropharyngeal aerosol and as nebulized large
      and fine droplet-sized pulmonary aerosols delivered by Pari and UltraVent
      nebulizers inhaled at fairly rapid and slow flows, respectively. Plasma
      concentration versus time profiles and 24-h urinary excretion of radioactivity
      were assessed. Further, 99mTc-labelled human serum albumin nanocolloidal
      particles (99mTc-Nanocoll) were administered with or without NaTC by Pari and
      followed by repeated chest gamma-imaging. RESULTS: NaTC changed no
      pharmacokinetic parameters for oropharyngeal 99mTc-DTPA. Independent of
      intrapulmonary 99mTc-DTPA deposition pattern, NaTC reduced Tmax (Pari: -0.8 h;
      UltraVent: -1.5 h) and mean absorption time (MAT) (-0.4 h; -0.7 h), and increased
      bioavailability (+13%; +44%) and dose-adjusted Cmax (+54%; +103%). NaTC decreased
      the pulmonary 99mTc-Nanocoll disappearance half-life from 8 h and 45 min to 4 h
      and 19 min. CONCLUSIONS: Our findings suggest that NaTC increases both rate and
      extent of 99mTc-DTPA absorption throughout the lower airways, without changing
      99mTc-DTPA absorption in the oral cavity.

PMID- 16902818
TI  - Fungal infection reduces herbivore-induced plant volatiles of maize but does not
      affect naive parasitoids.
AB  - Plants attacked by insects release volatile compounds that attract the
      herbivores' natural enemies. This so-called indirect defense is plastic and may
      be affected by an array of biotic and abiotic factors. We investigated the effect
      of fungal infection as a biotic stress agent on the emission of herbivore-induced
      volatiles and the possible consequences for the attraction of two parasitoid
      species. Maize seedlings that were simultaneously attacked by the fungus
      Setosphaeria turcica and larvae of Spodoptera littoralis emitted a blend of
      volatiles that was qualitatively similar to the blend emitted by maize that was
      damaged by only the herbivore, but there was a clear quantitative difference.
      When simultaneously challenged by fungus and herbivore, the maize plants emitted
      in total 47% less of the volatiles. Emissions of green leaf volatiles were
      unaffected. In a six-arm olfactometer, the parasitoids Cotesia marginiventris and
      Microplitis rufiventris responded equally well to odors of herbivore-damaged and
      fungus- and herbivore-damaged maize plants. Healthy and fungus-infected plants
      were not attractive. An additional experiment showed that the performance of S.
      littoralis caterpillars was not affected by the presence of the pathogen, nor was
      there an effect on larvae of M. rufiventris developing inside the caterpillars.
      Our results confirm previous indications that naive wasps may respond primarily
      to the green leaf volatiles.

PMID- 16902819
TI  - Photosynthesis and water relations in tomato plants cultivated long-term in media
      containing (+)-usnic acid.
AB  - The influence of (+)-usnic acid on rates of gas exchange (photosynthesis,
      respiration, and transpiration) in long-term cultivation of tomato plants was
      studied. The effect was dose-dependent. Plants grown in media containing the
      maximum concentration of (+)-usnic acid (30 muM) had photosynthetic and
      respiration rates reduced by 41% and 80%, respectively. The effect on
      photosynthesis rate may be the result of a multidirectional effect at various
      stages of this process, which at the highest usnic acid concentration underwent
      reduction: content of chlorophylls by 30%, carotenoids by 35%, and Hill reaction
      activity by 75%. Usnic acid also raises the susceptibility of chlorophyll to
      photodegradation. Under some conditions, transpiration was reduced by 2.1-fold in
      light and 3.7-fold in dark. This result was correlated with (1) an increase in
      the diffusive resistance of the stomata (3.1-fold in upper and 1.5-fold in lower
      surface of leaf), (2) a reduction of stomata density (by 60% on upper and 40% on
      lower surface), and (3) a 12.3-fold decrease in root hydraulic conductance.

PMID- 16902820
TI  - Chemical communication in Chagas disease vectors. Source, identity, and potential
      function of volatiles released by the metasternal and Brindley's glands of
      Triatoma infestans adults.
AB  - Compounds from the metasternal and Brindley's glands of the blood-sucking bug,
      Triatoma infestans, were identified by solid phase microextraction (SPME) and gas
      chromatography-mass spectrometry. Volatile compounds released by adult bugs
      during copulation or after mechanical disturbance were also characterized. Six
      compounds were identified and found consistently in all samples from metasternal
      glands. The most abundant were 3-pentanone, 2-methylbutanol, 3-pentanol, and an
      unidentified compound. The metasternal gland blends did not differ qualitatively
      between sexes. Compounds found in Brindley's glands were short chain acids,
      alcohols, esters, and a ketone with no qualitative differences between sexes.
      Isobutyric acid was the main component of this blend, and two new confirmed
      compounds were described as products of these glands: 2-butanone and 2
      methylbutyric acid. 3-Pentanone was collected from the headspace over 33% of the
      copulating pairs of T. infestans. Volatiles found in the headspace of disturbed
      T. infestans adults included short-chain fatty acids, alcohols, esters, and
      ketones, with no qualitative differences between sexes. Both types of glands
      apparently discharge their contents after disturbance. However, most of the
      volatiles released by bugs after disturbance came from Brindley's glands. The
      locomotor activity of fourth instars increased significantly after stimulation
      with the odors emitted by disturbed adults, as compared with larvae stimulated by
      the odor of undisturbed adults or by clean air. We also studied the directional
      behavioral response of fifth instars to the disturbance scent in a locomotion
      compensator. Larvae exposed to volatiles released by disturbed adults walked away
      from the direction of the odor. The results suggest that this blend or part of it
      functions as an alarm pheromone for T. infestans. We suggest that the metasternal
      glands of this species are involved both in the sexual and the alarm contexts,
      and that the Brindley's glands probably have both alarm and defensive roles.

PMID- 16902821
TI  - Cuticular hydrocarbons provide reliable cues of fertility in the ant Gnamptogenys
      striatula.
AB  - In ca. 150 species of queenless ants, a specialized queen caste is rare or
      absent, and mated workers take over the role of the queen in some or all of the
      colonies. Previously, it has been shown that reproduction in queenless ants is
      regulated by a combination of dominance behavior and chemical fertility
      signaling. It is unknown, however, whether chemical signals alone can
      sufficiently regulate reproduction. To investigate this possibility, we studied
      reproductive regulation in the facultatively queenless ant Gnamptogenys
      striatula, a species where dominance behavior is rare or absent. Active egg
      layers and infertile workers showed qualitative and quantitative differences in
      their cuticular hydrocarbon profile. Five long-chain methyl alkanes, 3,13- and
      3,15-dimethyl pentriacontane, 3,13- and 3,15-dimethyl heptentriacontane, and
      3,11,15-trimethyl heptentriacontane occurred only on the cuticles of virgin and
      mated egg layers. Pronounced quantitative differences were found in a further 27
      alkenes; alkanes; and mono-, di-, and trimethyl alkanes. Workers that had
      recently stopped laying eggs had profiles similar to infertile workers, and
      mating status did not affect this chemical pattern. We conclude that the
      cuticular hydrocarbon profiles of G. striatula workers provide reliable
      information about their current fertility. In the interest of colony
      productivity, this allows reproduction to be regulated without the use of
      aggression.

PMID- 16902822
TI  - Nest liquid resources of several cavity nesting bees in the genus Centris and the
      identification of a preservative, levulinic acid.
AB  - Twig-nesting species of bees in the genus Centris including C. bicornuta, C.
      analis, C. vittata, and C. nitida, found in the dry forest of Guanacaste Province
      of Costa Rica, provision their nests with pollen and nectar, rather than pollen
      and oil as reported for other Centris species. The liquid contents of the nests
      of these four species were found to contain sugars including 66-75% fructose, 25
      33% glucose, and a trace of sucrose. The sugar concentration averaged 47.2%,
      slightly higher than most flower nectars. No tri-, di-, or monoglycerides, the
      main components of the flower oil of Byrsonima crassifolia, were detected in the
      nest provisions. Although these four Centris species are also known to collect
      oil from B. crassifolia, the oil appears to be used for activities other than
      nest provisioning. The liquid nest contents did have a slight goat-like odor,
      suggesting the presence of short-chain fatty acids, and were found to contain a
      small amount (less than 1%) of three fatty acids. Two of these, butanoic and
      octanoic acid, were found in trace amounts and are responsible for the goat-like
      odor. A third was identified as levulinic acid, which made up about 99% of the
      nest fatty acid contents. This fatty acid had little odor, but may be important
      as a fungicidal agent. Attempts to determine the source of the fatty acids, were
      not successful.

PMID- 16902823
TI  - From terpenoids to aliphatic acids: further evidence for late-instar switch in
      osmeterial defense as a characteristic trait of swallowtail butterflies in the
      tribe papilionini.
AB  - We compared the chemical compositions of the osmeterial secretions of fourth and
      fifth (last) instars of eight swallowtail species of the tribe Papilionini. Four
      species (Papilio demoleus, P. polytes, P. paris, and P. macilentus) are Asian
      Rutaceae-feeding swallowtails. The other four (Chilasa epicydes, C. agestor, P.
      troilus, and P. glaucus) represent more distant clades within the Papilionini and
      species with larval hosts in other plant families. We conducted a quantitative
      analysis for six species, but only qualitative analysis for P. glaucus and C.
      agestor. In all eight species, regardless of larval host plant, secretions of the
      fourth instar principally consisted of mono- and sesquiterpene hydrocarbons,
      whereas those of the fifth instar comprised aliphatic acids and their esters.
      Consistent with earlier findings, our results suggest that this "heterogeneous"
      pattern of osmeterial chemistry, not seen in other tribes, may characterize the
      Papilionini as a whole. Unlike those of most Papilio species, the fourth and
      fifth instars of Chilasa species resemble each other in body coloration. Thus,
      the heterogeneous osmeterial pattern is not necessarily associated with color
      change in papilionid larvae. The major terpenoids identified in fourth instar
      larval secretions from the six species were alpha-pinene, sabinene, beta-myrcene,
      limonene, beta-phellandrene, (Z)-beta-ocimene, (E)-beta-ocimene, p-mentha-1,4(8)
      diene, beta-elemene, beta-caryophyllene, (E)-beta-farnesene, (3Z,6E)-alpha
      farnesene, (Z)-alpha-bisabolene, germacrene-A, (E)-alpha-bisabolene, and
      germacrene-B. The profiles for individual species differed both qualitatively and
      quantitatively from one another, and certain species also secreted methyl 3
      hydroxy-n-butyrate and oxygenated sesquiterpenes in relatively large proportions.
      Secretions from fifth instars were composed of varying proportions of isobutyric,
      2-methylbutyric, and acetic acids, and methyl and ethyl (minor) esters of both
      isobutyric and 2-methylbutyric acids. The heterogeneity of osmeterial chemistry
      in the tribe Papilionini may represent fine-tuning of chemical defense in
      response to shifting predation pressures as the larvae age and grow.

PMID- 16902824
TI  - Chemically mediated intraguild predator avoidance by aphid parasitoids:
      interspecific variability in sensitivity to semiochemical trails of ladybird
      predators.
AB  - The avoidance responses of aphid parasitoids with varying host ranges (Aphidius
      eadyi, Aphidius ervi, and Praon volucre) to chemical trails deposited by
      intraguild predatory ladybirds, Coccinella septempunctata and Adalia bipunctata,
      were investigated. Females of all three parasitoid species avoided leaves
      previously visited by C. septempunctata or A. bipunctata adults. The avoidance
      responses shown by the two Aphidius species were stronger to trails of C.
      septempunctata than to those of A. bipunctata. However, P. volucre avoided trails
      of both ladybird species to a similar degree. Dose responses of these three
      parasitoid species to the hydrocarbons n-tricosane (C23H48), n-pentacosane
      (C25H52), and n-heptacosane (C27H56), which are components of the trails of both
      C. septempunctata and A. bipunctata, were evaluated. Dual-choice bioassays
      indicated the following: (1) A. eadyi showed more sensitive avoidance responses
      to n-tricosane than did the other two parasitoid species, (2) all three species
      showed similar responses to n-pentacosane across a range of doses, and (3) only
      P. volucre showed avoidance responses to n-heptacosane. Quantitative analyses of
      each hydrocarbon in the trails of the two ladybird species showed that n
      pentacosane and n-heptacosane occur in significantly greater amounts in C.
      septempunctata trails than in those of A. bipunctata. The trails of the two
      species also differ qualitatively in the other hydrocarbons present.

PMID- 16902825
TI  - Analyses of avocado (Persea americana) nectar properties and their perception by
      honey bees (Apis mellifera).
AB  - Honey bees are important avocado pollinators. However, due to the low
      attractiveness of flowers, pollination is often inadequate. Previous work has
      revealed that avocado honey is relatively unattractive to honey bees when
      compared with honey from competing flowers. We characterized avocado honey and
      nectar with respect to their odor, color, and composition of sugars, phenolic
      compounds, and minerals. Furthermore, we tested how honey bees perceive these
      parameters, using the proboscis extension response bioassay and preference
      experiments with free-flying bees. Naive bees were indifferent to odors of
      avocado and citrus flowers and honey. Experienced bees, which were collected in
      the field during the blooming season, responded preferentially to odor of citrus
      flowers. The unique sugar composition of avocado nectar, which contains almost
      exclusively sucrose and a low concentration of the rare carbohydrate perseitol,
      and the dark brown color of avocado honey, had no negative effects on its
      attractiveness to the bees. Phenolic compounds extracted from avocado honey were
      attractive to bees and adding them to a solution of sucrose increased its
      attractiveness. Compared with citrus nectar and nonavocado honey, avocado nectar
      and honey were rich in a wide range of minerals, including potassium, phosphorus,
      magnesium, sulfur, iron, and copper. Potassium and phosphorus, the two major
      minerals, both had a repellent effect on the bees. Possible explanations for the
      presence of repellent components in avocado nectar are discussed.

PMID- 16902826
TI  - Reaction of mutualistic and granivorous ants to ulex elaiosome chemicals.
AB  - It has been proposed that chemicals on plant elaiosomes aid seed detection by
      seed-dispersing ants. We hypothesized that the chemical interaction between ants
      and elaiosomes is more intimate than a generic attraction, and that elaiosome
      chemicals will attract mutualistic but not granivorous ant species. We
      investigated this by using two gorse species, Ulex minor and U. europaeus, and
      two associated ant species from European heathlands, the mutualist Myrmica
      ruginodis and the granivore Tetramorium caespitum. Behavioral studies were
      conducted with laboratory nests and foraging arenas. Both ants will take Ulex
      seeds, but while M. ruginodis showed increased antennation toward ether extracts
      of elaiosome surface chemicals compared with controls, T. caespitum showed no
      response. Elaiosome extracts were separated into seven lipid fractions. M.
      ruginodis showed increased antennation only toward the diglyceride fractions of
      both Ulex species, whereas T. caespitum showed no consistent reaction. This
      indicates that M. ruginodis can detect the elaiosome by responding to its surface
      chemicals, but T. caespitum is unresponsive to these chemicals. Responses to
      surface chemicals could increase the rate of seed detection in the field, and so
      these results suggest that Ulex elaiosomes produce chemicals that facilitate
      attraction of mutualistic rather than granivorous ant species. This could reduce
      seed predation and increase Ulex fitness.

PMID- 16902827
TI  - Lonicera Implexa leaves bearing naturally laid eggs of the specialist herbivore
      Euphydryas Aurinia have dramatically greater concentrations of iridoid glycosides
      than other leaves.
AB  - We tested in the field the hypothesis that the specialist butterfly Euphydryas
      aurinia (Lepidoptera: Nymphalidae, Melitaeinae) lays eggs on leaves of Lonicera
      implexa (Caprifoliaceae) plants with greater iridoid concentrations. We conducted
      our investigations in a Mediterranean site by analyzing leaves with and without
      naturally laid egg clusters. There were no significant differences in iridoid
      glycoside concentrations between leaves from plants that did not receive eggs and
      the unused leaves from plants receiving eggs, a fact that would seem to indicate
      that E. aurinia butterflies do not choose plants for oviposition by their iridoid
      content. However, the leaves of L. implexa that bore egg clusters had
      dramatically greater (over 15-fold) concentrations of iridoid glycosides than the
      directly opposite leaves on the same plant. These huge foliar concentrations of
      iridoids (15% leaf dry weight) may provide specialist herbivores with compounds
      that they either sequester for their own defense or use as a means of avoiding
      competition for food from generalist herbivores. Nevertheless, it may still be
      possible that these high concentrations are detrimental to the herbivore, even if
      the herbivore is a specialist feeder on the plant.

PMID- 16902828
TI  - Attraction of Spodoptera frugiperda larvae to volatiles from herbivore-damaged
      maize seedlings.
AB  - Plants respond to insect attack with the induction of volatiles that function as
      indirect plant defenses through the attraction of natural enemies to the
      herbivores. Despite the fact that volatiles are induced in response to
      caterpillar attack, their reciprocal effects on the host location behaviors of
      the same foraging herbivores are poorly understood. We examined orientation
      responses of sixth instar fall armyworm [FAW; Spodoptera frugiperda (Smith)] to
      odors from herbivore-damaged and undamaged maize seedlings (Zea mays var. Golden
      Queen) in y-tube olfactometer bioassays. While both damaged and undamaged maize
      seedlings were attractive compared with air, sixth instars preferred odors from
      damaged maize seedlings over odors from undamaged maize seedlings. Gas
      chromatography-mass spectrometry analysis of plant volatiles revealed that
      linalool and 4,8-dimethyl-1,3,7-nonatriene were the major volatiles induced by
      FAW herbivory 6 hr after initial damage. Given its prominence in induced plants
      and established attractiveness to adult FAW, linalool was evaluated both as an
      individual attractant and as a supplemental component of whole plant odors.
      Volatile linalool was more attractive than air to sixth instar FAW over a broad
      range of release rates. FAW also responded selectively to different amounts of
      linalool, preferring the higher amount. The orientation preferences of FAW were
      readily manipulated through capillary release of linalool into the airstream of
      whole plant odors. FAW preferred linalool over undamaged plant odors, and
      linalool-supplemented plant odors over unsupplemented plant odors, indicating
      that olfactory preferences could be changed by alteration of a single volatile
      component. These results suggest that although many induced volatiles attract
      natural enemies of herbivores, these defenses may also inadvertently recruit more
      larval herbivores to an attacked plant or neighboring conspecifics.

PMID- 16902829
TI  - Volatile foraging kairomones in the littoral zone: attraction of an herbivorous
      freshwater gastropod to algal odors.
AB  - Volatile organic compounds (VOCs) produced by algae and cyanobacteria are
      primarily responsible for odors in fresh waters. Among other functions, VOCs may
      serve as important infochemicals in biofilms of benthic primary producers. VOCs
      liberated by benthic, mat-forming cyanobacteria can be used as habitat-finding
      cues by insects, nematodes, and possibly other organisms. We developed a new
      gastropod behavioral assay that allows detection of food preference without
      offering food, thus allowing the distinction between taste, which requires direct
      contact with the food source, and the detection of odorous infochemicals, which
      work over distance. We demonstrated that VOCs released from disintegrated cells
      of a benthic, mat-forming, green alga (Ulothrix fimbriata) are food-finding cues
      ("foraging kairomones") that attract the herbivorous freshwater snail Radix
      ovata. A mixture of three C5 lipoxygenase compounds and 2(E),4(E)-heptadienal
      that mimic the major VOCs released by U. fimbriata attracted the snails, whereas
      neither the mixture of C5 compounds nor 2(E),4(E)-heptadienal were effective when
      given alone. This study suggests that VOCs can play a steering role as
      infochemicals in freshwater benthic habitats, as has been established for many
      organismic interactions in terrestrial ecosystems.

PMID- 16902831
TI  - Gun control in the UK--still a matter for debate.

PMID- 16902830
TI  - Analysis of the sex ratio in preimplantation embryos from B6.K1 and B6.K2 Ped
      gene congenic mice.
AB  - PURPOSE: The mouse preimplantation embryo development (Ped) gene product, Qa-2,
      which is the homolog of human HLA-G, influences the rate of preimplantation
      embryonic development and overall reproductive success. The sex ratio in
      preimplantation embryos from Ped gene congenic mice was examined in order to
      determine whether embryo sex is a confounding factor in the control of the rate
      of preimplantation development. METHODS: B6.K1 (Ped slow) and B6.K2 (Ped fast)
      congenic mice differ only in the absence (B6.K1) or presence (B6.K2) of the genes
      encoding Qa-2 protein. We analyzed the sex of B6.K1 (n=221) and B6.K2 (n=260)
      preimplantation embryos by using Real-Time PCR with primers specific for the X
      and Y chromosomes. RESULTS: We found that there was no statistically significant
      difference in the ratio of male to female preimplantation embryos in either
      strain. CONCLUSIONS: We conclude that the sex of the embryos is not a confounding
      factor that affects the Ped gene control of the rate of preimplantation
      development. Therefore, the Ped gene is entirely responsible for mediating the
      faster development of B6.K2 embryos compared to B6.K1 embryos.

PMID- 16902833
TI  - Mild, moderate and severe versus insignificant and significant.

PMID- 16902832
TI  - The management of 38 anastomotic leaks after 1,684 intestinal resections.
AB  - PURPOSE: This study was designed to evaluate the management of anastomotic leaks
      and assess the impact of outpatient leak presentation on clinical outcome.
      METHODS: Thirty-eight patients with clinical anastomotic leaks from 1,684 adult
      patients undergoing large and small intestinal anastomosis in a tertiary referral
      center between January 1, 2003 and September 1, 2005 were studied. All pediatric
      patients and adult patients with esophageal and gastric leaks were excluded.
      Charts were reviewed for information on anastomotic leak management, discharge
      status before leak presentation, length of stay, readmissions, and mortality.
      RESULTS: The overall leak rate was 2.3 percent. Eighty-seven percent of patients
      (n = 33) were managed operatively. Forty-two percent of patients (n = 16) were
      discharged after initial operation and presented as outpatients with anastomotic
      leak. The discharge and inpatient groups were comparable in respect to total
      length of stay (26.9 vs. 33.4 days) and number of readmissions (2 vs. 1.5). The
      overall mortality of 5 percent (n = 2) originated from the discharge group. A
      greater percentage of discharge patients required intensive care unit stays for
      more than two weeks (25 vs. 14 percent) and very long hospital admissions lasting
      more than two months (31 vs. 9 percent). A smaller percentage of the discharge
      group patients had their ostomies reversed (31 vs. 50 percent). CONCLUSIONS: The
      primary management of clinical anastomotic leak remains intestinal diversion.
      Although length of stay was shorter in the discharge group, the number of
      patients who experienced significant intensive care unit stays and very long
      hospital stays was greater. Within the discharge group, mortality was higher and
      fewer patients had their ostomies reversed.

PMID- 16902836
TI  - Tissue Doppler evaluation of tricuspid annulus for estimation of pulmonary artery
      pressure in patients with COPD.
AB  - Because transthoracic echocardiography is an inexpensive, easy, and reproducible
      method, it is the most commonly used noninvasive diagnostic tool to determine
      pulmonary artery pressure (PAP). Tissue Doppler imaging (TDI) emerged as a new
      echocardiographic method that can be applied in various clinical conditions. In
      our study we aimed to evaluate the relationship between tricuspid lateral annulus
      TDI parameters and pulmonary artery systolic pressure (PASP) as estimated by
      continuous wave Doppler in patients with chronic obstructive pulmonary disease
      (COPD). A total of 51 (42 men, mean age: 62.3 +/- 8.2 years) patients with
      clinically stable COPD were included in the study. The tricuspid annular systolic
      myocardial velocity (Sm), velocity time integral of Sm (SmVTI), early (Em) and
      late (Am) peak diastolic myocardial velocities, and myocardial isovolumic
      relaxation time (IVRTm) were acquired as well as two-dimensional (2-D) and
      conventional Doppler data. When compared with values of patients without
      pulmonary hypertension (PHT), Sm, SmVTI, Em, and Em/Am values were found to be
      lower and IVRTm values higher in patients with PHT. When all the patients were
      analyzed, there was a significant negative correlation between PASP and Sm and
      SmVTI (r = -0.82, p < 0.001 and r = -0.84, p < 0.001, respectively). Sm velocity
      < or = 12 cm/s had a sensitivity of 85% and a specificity of 93.3% for predicting
      PASP > 40 mmHg. SmVTI < or = 2.5 cm had a sensitivity of 85.7% and a specificity
      of 90% for detecting PHT. In our study, there was significant negative
      correlation between tricuspid lateral annular Sm and SmVTI values and PASP in
      patients with stable COPD irrespective of the presence of PHT. Tricuspid annular
      Sm and SmVTI had very good level sensitivity and specificity for predicting PHT.
      In conclusion, it might be suggested that in cases where noninvasive PASP
      measurement is not possible, TDI can be used as an alternative and reliable
      method to assess PAP.

PMID- 16902837
TI  - Phase I/II trial of docetaxel and carboplatin as a first-line therapy in patients
      with stage IV non-small-cell lung cancer.
AB  - A phase I/II study was conducted to determine the maximum-tolerated dose, the
      safety and tolerability, and the clinical efficacy of carboplatin and docetaxel
      in combination in patients with stage IV non-small-cell lung cancer. Patients
      with measurable, previously untreated, good performance status, and stage IV non
      small-cell lung cancer were eligible. Increasing doses of docetaxel were given in
      combination with a fixed dose of carboplatin except at level 5. Cycles were
      repeated every four weeks. Seventy-seven patients were registered. In phase I, 27
      patients were entered at five different dose levels. A docetaxel dose of 60
      mg/m(2) and carboplatin area under the concentration time curve 6 was recommended
      for phase II, and an additional 50 patients were entered at this level for a
      total of 56 patients. Grade 3/4 neutropenia was the most common adverse event and
      occurred in 70% of the patients. Two patients had febrile neutropenia. Fifty-six
      patients were assessable for response; 21 partial responses were observed for an
      overall response rate of 37.5%. The median time to tumor progression was 4.0
      months (range, 1.0-21.0 months), and the median survival was 12.9 months (range,
      0.4-51.3 months). The one-year survival rate was 46.4%. The combination of
      docetaxel 60 mg/m(2) and carboplatin area under the concentration time curve 6 is
      feasible and effective in patients with stage IV non-small-cell lung cancer.

PMID- 16902838
TI  - Role of pleural fluid C-reactive protein concentration in discriminating
      uncomplicated parapneumonic pleural effusions from complicated parapneumonic
      effusion and empyema.
AB  - The aim of this study was to determine whether pleural fluid C-reactive protein
      (CRP) is useful in distinguishing complicated parapneumonic pleural effusion
      (CPPE) and empyema from uncomplicated parapneumonic pleural effusions (UPPE). A
      total of 69 consecutive patients with parapneumonic effusions were enrolled in
      the study: 29 with UPPE, 29 with CPPE, and 11 with empyema. Concentrations of
      standard biochemical parameters together with CRP in the pleural fluid were
      measured using an immunoturbidimetric assay. Pleural CRP was significantly higher
      in CPPE (11.6 mg/dl) and in empyema (12.2 mg/dl) than in UPPE (3.9 mg/dl). A
      cutoff value of 8.7 mg/dl for pleural CRP in the diagnosis of CPPE and empyema
      resulted in a sensitivity, specificity, and area under the receiver-operating
      characteristic curve (AUC) of 0.80, 0.97 and 0.94, respectively. Traditional
      lactic dehydrogenase (LDH) > or = 1000 U/L and glucose < or = 60 mg/dl can
      differentiate CPPE and empyema from UPPE, with the sensitivity, specificity, and
      AUC achieving 0.75/0.60.1.00/1.00,0.95/0.22, respectively. However, for the
      detection of CPPE and empyema, the combination of pleural fluid CRP > or = 8.7
      mg/dl and LDH > or = 1000 U/L was valuable in achieving a sensitivity,
      specificity, and AUC of 0.97/1,00/0.95. This study suggests that measurement of
      pleural CRP can be useful in the workup of patients with a parapneumonic effusion
      in order to differentiate CPPE from UPPE.

PMID- 16902839
TI  - Giant cell interstitial pneumonia associated with nitrofurantoin.
AB  - A case of giant cell interstitial pneumonia (GIF) that occurred in association
      with exposure to nitrofurantoin is presented. While the diagnosis of GIP is
      confirmed by histopathology, this diagnosis can be supported by the findings of
      bizarre multinucleated giant cells (MGC), elevated T lymphocytes, and a low T
      lymphocyte helper/suppressor ratio in the bronchoalveolar lavage fluid (BALF).
      Recognition of GIP as a rare manifestation of nitrofurantoin toxicity is
      important because prompt therapy may be associated with a favorable outcome.

PMID- 16902840
TI  - Does the inclusion of wheeze detection as an outcome measure affect the
      interpretation of methacholine challenge tests? A study in workers at risk of
      occupational asthma.
AB  - Methacholine challenge testing (MCT) is widely used to assess airway
      hyperresponsiveness (AHR). Traditionally, a 20% or greater decline in forced
      expiratory volume in 1 (FEV(1)) is the primary outcome measure. We examined
      whether the inclusion of wheeze detection as outcome measure influenced the
      categorical interpretation of MCT in workers at risk of occupational asthma (OA).
      We examined 28 occupationally exposed smokers with asthma-like symptoms
      (SympAsth), 22 asymptomatic, occupationally exposed smokers (Symp0), and 30
      nonexposed, asymptomatic controls (Ctrl). MCT was done using an abbreviated
      technique. Spirometry and tracheal wheezes were recorded using a computerized
      system. MCT was considered either positive or negative using three outcome
      measures separately: (1) > or = 20% fall in FEV(1) (MCT("FEV1")); (2) wheeze
      appearance (MCT("Wheeze")); and (3) whichever among the two was present
      (MCT("FEV1Wheeze")). The proportion of reactors in each group were, by outcome
      measure, as follows: MCT("FEV1"): Ctrl = 2 (6.7%), Symp0 = 6 (27.3%), SympAsth =
      l2 (42.8%) (chi(2) = 10.2; p = 0.006); MCT("Wheeze"): Ctrl = 1 (3.3%), Symp0 = 4
      (18.2%), SympAsth = 13 (46.4%) (chi(2) = l5.7; p = 0.001); MCT("FEV1Wheeze") Ctrl
      = 2 (6.7%), Symp0 = 7 (31.8%), SympAsth = 18 (64.3%) (chi(2) = 21.5; p = 0.001).
      Overall, including wheeze detection increased the proportion of "reactors"
      detected by spirometry by 30% (27 reactors vs. 20). This increase reached 50% (18
      vs. 12) among workers with asthma like symptoms. In summary, the inclusion of
      wheeze detection as outcome measure for MCT allowed the recognition as reactors
      of subjects that otherwise would be "missed" by spirometry. The resulting
      increase in the number of true positives improved the sensitivity of MCT to
      detect AHR in occupationally exposed workers at risk of occupational asthma.

PMID- 16902841
TI  - A controlled trial of the effects of leg training on breathing pattern and
      dynamic hyperinflation in severe COPD.
AB  - The effects of training on dynamic hyperinflation in stable chronic obstructive
      pulmonary disease (COPD) were investigated by using a controlled study of 28
      subjects with FEV(1) = 42.5 (8.3 SD)%pred and 20 matched controls [FEV(1) = 44.9
      (10.4)%pred]. Training consisted of spending 45 min/day, 4 days/week on a cycle
      ergometer for six weeks. Maximal inspiratory and expiratory pressures (MIP and
      MEP), lung volumes, and two constant-work-rate (CWR) exercise tests (low- and
      high-intensity) were performed. Significant (p < 0.0l) improvements in the
      training group were observed in MIP [+8 (12) cmH(2)O], MEP [+18 (20) cmH(2)O],
      and endurance to high-intensity CWR [+7(5) min], and there were significant
      decreases in respiratory rate and end-expiratory lung volume (EELV) during both
      exercise tests. At 5 min, EELV decreased 0.1(0.08) L and 0.31(0.13) L and at end
      of exercise, EELV decreased by 0.09(0.07) L and 0.15(0.11) L respectively, for
      the moderate- and high-intensity tests. Dyspnea also decreased significantly at
      both exercise intensities. No changes were observed in the control group.
      Increased endurance showed independent significant (p < 0.05) correlation with
      changes in EELV, leg fatigue, and MEP. EELV changes showed a significant negative
      correlation with resting inspiratory capacity. We conclude that exercise training
      has beneficial effects on respiratory pattern and dynamic hyperinflation that may
      partially explain the reduction in dyspnea and the improvement in exercise
      tolerance.

PMID- 16902842
TI  - An update on interventional lung assist devices and their role in acute
      respiratory distress syndrome.
AB  - In recent years, pumpless arteriovenous systems for extracorporeal gas exchange
      have become a new therapeutic option for the treatment of patients suffering from
      acute respiratory failure. Experiences with the pumpless extracorporeal membrane
      lung in animal experiments and in patients with adult respiratory distress
      syndrome published in the current literature are reviewed. In addition this
      article presents a case of varicella pneumonia with persistent hypoxemia and
      hypercapnia under mechanical ventilation that showed a significant improvement
      with treatment with a pumpless extracorporeal lung assist using an arteriovenous
      shunt for eight days. The patient made a complete recovery. This is the first
      report of a patient with a life-threatening varicella pneumonia successfully
      treated with pumpless extracorporeal lung assist device. This review provides an
      update on interventional lung assist devices and a critical discussion of their
      advantages and limitations.

PMID- 16902843
TI  - Transfusion-related acute lung injury (TRALI): current clinical and
      pathophysiologic considerations.
AB  - Transfusion-related acute lung injury (TRALI) is a rare transfusion reaction
      presenting as respiratory distress during or after transfusion of blood products.
      TRALI varies in severity, and mortality is not uncommon. TRALI reactions have
      equal gender distributions and can occur in all age groups. All blood products,
      except albumin, have been implicated in TRALI reactions. TRALI presents as acute
      respiratory compromise occurring in temporal proximity to a transfusion of a
      blood product. Other causes of acute lung injury should be excluded in order to
      definitively diagnose TRALI. Clinically and pathologically, TRALI mimics acute
      respiratory distress syndrome (ARDS), with neutrophil-derived inflammatory
      chemokines and cytokines believed to be involved in the pathogenesis of both
      entities. Anti-HLA and anti-neutrophil antibodies have been implicated in some
      cases of TRALI. Treatment for TRALI is supportive; prevention is important. It is
      suspected that TRALI is both underdiagnosed and underreported. One of the
      difficulties in the evaluation of potential TRALI reactions is, until recently,
      the lack of diagnostic criteria. A group of transfusion medicine experts, the
      American-European Consensus Conference (AECC), recently met and developed
      diagnostic criteria of TRALI, as well as recommendations for management of donors
      to prevent future TRALI reactions. In light of the AECC consensus
      recommendations, we report an incident of TRALI in an oncology patient as an
      example of the potential severity of the lung disease and the clinical and
      laboratory evaluation of the patient. We also review the literature on this
      important complication of blood transfusion that internists may encounter.

PMID- 16902845
TI  - Improved production of an enzyme that hydrolyses raw yam starch by Penicillium
      sp. S-22 using fed-batch fermentation.
AB  - A newly isolated strain, Penicillium sp. S-22, was used to produce an enzyme that
      hydrolyses raw yam starch [raw yam starch digesting enzyme (RYSDE)]. The enzyme
      activity and overall enzyme productivity were respectively 16 U/ml and 0.19 U/ml
      h in the batch culture. The enzyme activity increased to 85 U/ml by feeding of
      partially hydrolyzed raw yam starch. When a mixture containing partially
      hydrolyzed raw yam starch and peptone was fed by a pH-stat strategy, the enzyme
      activity reached 366 U/ml, 23-fold of that obtained in the batch culture, and the
      overall productivity reached 3.4 U/ml h, which was 18-fold of that in the batch
      culture.

PMID- 16902844
TI  - An intradural extramedullary tuberculoma of the spinal cord in a non-HIV-infected
      patient: case report and review of the literature.
AB  - Spinal tuberculomas are extrapulmonary manifestations of tuberculosis involving
      the central nervous system. They are characterized as extradural, intradural
      extramedullary, or intradural, according to their location. Intradural
      extramedullary tuberculomas are extremely rare. There have been only 24 case
      reports found in English language literature. Our case is the only documented
      intradural extramedullary tuberculoma in a non-HIV-infected patient in North
      America. A literature review using a Medline search from 1966 to the present is
      performed to characterize the clinical spectrum of the three types of
      tuberculomas and review the diagnosis and management of this potentially curable
      disease. An analysis of the cases of intradural extramedullary tuberculomas
      published since 1984 is performed to highlight the unique characteristics of this
      rare disease.

PMID- 16902846
TI  - Natural and engineered ribonucleases as potential cancer therapeutics.
AB  - By reason of their cytotoxicity, ribonucleases (RNases) are potential anti-tumor
      drugs. Particularly members from the RNase A and RNase T1 superfamilies have
      shown promising results. Among these enzymes, Onconase, an RNase from the
      Northern Leopard frog, is furthest along in clinical trials. A general model for
      the mechanism of the cytotoxic action of RNases includes the interaction of the
      enzyme with the cellular membrane, internalization, translocation to the cytosol,
      and degradation of ribonucleic acid. The interplay of these processes as well as
      the role of the thermodynamic and proteolytic stability, the catalytic activity,
      and the capability of the RNase to evade the intracellular RNase inhibitor has
      not yet been fully elucidated. This paper discusses the various approaches to
      exploit RNases as cytotoxic agents.

PMID- 16902847
TI  - Redifferentiation of chondrocytes and cartilage formation under intermittent
      hydrostatic pressure.
AB  - Since articular cartilage is subjected to varying loads in vivo and undergoes
      cyclic hydrostatic pressure during periods of loading, it is hypothesized that
      mimicking these in vivo conditions can enhance synthesis of important matrix
      components during cultivation in vitro. Thus, the influence of intermittent
      loading during redifferentiation of chondrocytes in alginate beads, and during
      cartilage formation was investigated. A statistically significant increased
      synthesis of glycosaminoglycan and collagen type II during redifferentiation of
      chondrocytes embedded in alginate beads, as well as an increase in
      glycosaminoglycan content of tissue-engineered cartilage, was found compared to
      control without load. Immunohistological staining indicated qualitatively a high
      expression of collagen type II for both cases.

PMID- 16902848
TI  - Fed-batch two-phase production of alanine by a metabolically engineered
      Escherichia coli.
AB  - DL-Alanine was produced from glucose in an Escherichia coli pfl pps poxB ldhA
      aceEF pTrc99A-alaD strain which lacked pyruvate-formate lyase,
      phosphoenolpyruvate (PEP) synthase, pyruvate oxidase, lactate dehydogenase,
      components of the pyruvate dehydogenase complex and over-produced alanine
      dehydrogenase (ALD). A two-phase process was developed with cell growth under
      aerobic conditions followed by alanine production under anaerobic conditions.
      Using the batch mode, cells grew to 5.3 g/l in 9 h with the accumulation of 6-10
      g acetate/l, and under subsequent anaerobic conditions achieved 34 g alanine/l in
      13 h with a yield of 0.86 g/g glucose. Using the fed-batch mode at micro = 0.15
      h(-1), only about 1 g acetate/l formed in the 25 h required for the cells to
      reach 5.6 g/l, and 88 g alanine/l accumulated during the subsequent 23 h. This
      fed-batch process attained an alanine volumetric productivity of 4 g/lh during
      the production phase, and a yield that was essentially 1 g/g.

PMID- 16902849
TI  - Expression and purification of a soluble B lymphocyte stimulator mutant modified
      with the T-helper cell epitope.
AB  - The DNA encoding soluble B lymphocyte stimulator (134-285 amino acids, sBLyS)
      mutant with residues 217-224 replaced by two glycines (named msBLyS) was
      constructed. The sequence encoding a foreign immunodominant T-helper epitope from
      ovalbumin (OVA) was then coupled to the 5'-end of msBLyS cDNA. After being
      sequenced, the recombinant DNA was ligated into the prokaryotic expression vector
      pQE-80L. The recombinant protein was produced in E. coli DH5alpha after induction
      with IPTG with the yield of more than 40% of total bacterial protein. The
      recombinant protein was purified with Ni-NTA chromatography and Sepharcryl S200
      chromatography to a purity of more than 98%. The BALB/c mice, immunized with the
      recombinant protein, produced anti-BLyS antibodies at a high level, which
      indicated that the recombinant BLyS mutant modified with T-helper epitope
      elicited polyclonal antibodies with cross-reactivity with BLyS in vivo. This
      recombinant protein may therefore be used as immune inhibitor of BLyS for
      treating BLyS -associated autoimmune diseases.

PMID- 16902850
TI  - An optimal pooling strategy applied to high-throughput screening for rare marker
      free transformants.
AB  - An optimal pooling system, called Accurate and Fast Target Screening, has been
      developed for high-throughput identifying the rare marker-free transformants.
      This system can identify targets between 10- and 100-fold more efficiently than
      analysis of individual samples. By calculating the efficiency for different
      proportions of targets and the optimal group size in a worst case scenario, we
      are able to estimate an upper limit for the number of tests that are required.
      The application of this system to determine the transgene in an artificially
      constructed population of transgenic and non-transgenic wheat lines successfully
      identified the 10 positive samples located randomly with 990 negative samples
      using only 92 PCR reactions. The same approach was also applied to determine
      transgene expression by SDS-PAGE of seed proteins. This system gives unambiguous
      positive or negative results and should facilitate marker-free transformation.

PMID- 16902851
TI  - Impulsive vaccination of an SEIRS model with time delay and varying total
      population size.
AB  - Pulse vaccination is an effective and important strategy for the elimination of
      infectious diseases. A delayed SEIRS epidemic model with pulse vaccination and
      varying total population size is proposed in this paper. We point out, if R* < 1,
      the infectious population disappear so the disease dies out, while if R(*) > 1,
      the infectious population persist. Our results indicate that a long period of
      pulsing or a small pulse vaccination rate is sufficient condition for the
      permanence of the model.

PMID- 16902852
TI  - Authentication is fundamental for standardization of Chinese medicines.
AB  - Chinese medicines (CMs) are being used more and more widely throughout the world.
      Since there are many poisoning incidents caused by misuse or confusion of CMs,
      their safe use has become a critical issue internationally. In this paper, based
      on the investigation of the current market of CMs, reasons for various confusions
      of Chinese Materia Medica (CMM) are analyzed and clarified, such as herbs with
      multiple sources, regional custom-herbs, confusion in nomenclature, similarity in
      appearance, and complexity of processed products. Authentication of plant
      material is critical to the safe and effective use of CMM. In this paper, several
      authentication methods, such as taxonomy, morphology, microscopy, physical and
      chemical authentication, DNA molecular biology and their advanced applications in
      this area, are introduced. Furthermore, it is proposed that an authority on the
      authentication of CMM be established, as a physical institution and/or as an
      electronic database.

PMID- 16902853
TI  - Cardenolide genin pattern in Isoplexis plants and shoot cultures.
AB  - An HPLC method for the quantitative analysis of cardenolides was developed and
      applied. The procedure was optimised for analysing small samples (40 mg dw) of
      plant and tissue culture material. ISOPLEXIS CANARIENSIS plants obtained from
      seeds accumulated cardenolides to about 20 - 40 micromol g (-1) dw as calculated
      from the levels of cardenolide genins released after acidic hydrolysis of
      methanolic extracts. The relative contents of xysmalogenin, digitoxigenin,
      uzarigenin and canarigenin were 5 - 15 %, 0 - 5 %, 10 - 15 % and 70 - 90 %,
      respectively. Shoot cultures were initiated from seeds, established as permanent
      cultures and cultivated on agar-solidified or in liquid medium. Shoot cultures
      maintained on solid medium contained an average of about 6 micromol cardenolides
      g (-1) dw. A relatively high proportion of digitoxigenin was found in two-thirds
      of the shoot cultures examined. The cardenolide content of amphibian shoot
      cultures averaged to about 1 micromol g (-1) dw. Plants regenerated from shoot
      cultures and maintained under hydroponic conditions accumulated the same amount
      of cardenolides as plants collected in the field. No cardenolides could be
      detected in callus cultures.

PMID- 16902855
TI  - Isolation and antimalarial activity of alkaloids from Pseudoxandra cuspidata.
AB  - A novel and very unusual azaanthracene alkaloid, 1-aza-7,8,9,10-tetramethoxy-4
      methyl-2-oxo-1,2-dihydroanthracene ( 1) and a new diastereoisomer of the bis
      benzylisoquinoline alkaloid rodiasine, 1 S,1' R-rodiasine ( 2), as well as the
      alkaloids O-methylpunjabine ( 3) and O-methylmoschatoline ( 4) have been isolated
      from Pseudoxandra cuspidata bark, used in French Guiana as an antimalarial. Their
      structures were elucidated by spectroscopic analyses, especially 2D-NMR
      techniques (ADEQUATE and NOESY). We found that the antimalarial activity of this
      bark was mostly due to bis-benzylisoquinoline 1 S,1' R-rodiasine ( 2) (IC (50)= 1
      microM) also displaying a low cytotoxicity.

PMID- 16902856
TI  - Antiviral effect of artemisinin from Artemisia annua against a model member of
      the Flaviviridae family, the bovine viral diarrhoea virus (BVDV).
AB  - The antiviral activity versus flaviviruses of artemisinin, a safe drug obtained
      from Artemisia annua and commonly used to treat malaria, has been investigated
      using as an IN VITRO model bovine epithelial cells from embryonic trachea (EBTr)
      infected with the cytopathic strain Oregon C24V, of bovine viral diarrhoea virus
      (BVDV), which is a member of the Flaviviridae family. Antiviral activity was
      estimated by the degree of protection against the cytopathic effect of BVDV on
      host cells and by the reduction in BVDV-RNA release to the culture medium. To
      induce an intermediate cytopathic effect in non-treated cells, EBTr cells were
      first exposed to BVDV for 48 h and then incubated with virus-free medium for 72
      h. Ribavirin and artemisinin (up to 100 microM) induced no toxicity in host
      cells, whereas a slight degree of toxicity was observed for IFN-alpha at
      concentrations above 10 U/mL up to 100 U/mL. Treatment of infected cells with IFN
      alpha, ribavirin and artemisinin markedly reduced BVDV-induced cell death. A
      combination of these drugs resulted in an additive protective effect. These drugs
      induced a significant reduction in the production/release of BVDV virions by
      infected EBTr cells; there was also an additive effect when combinations of them
      were assayed. These results suggest a potential usefulness of artemisinin in
      combination with current pharmacological therapy for the treatment of human and
      veterinary infections by flaviviruses.

PMID- 16902858
TI  - Evaluation of the analgesic and anti-inflammatory effects of a Brazilian green
      propolis.
AB  - Phamacological activities of a standard ethanol extract G1 from Brazilian green
      propolis, typified as BRP1, was evaluated in mouse models of pain and
      inflammation. Intraperitoneal injection ( I. P.) of G1 inhibited acetic acid
      induced abdominal constrictions with an ID (50) = 0.75 +/- 0.05 mg/kg, and in the
      formalin test the ID (50) values were 0.85 +/- 0.07 mg/kg and 13.88 +/- 1.12
      mg/kg, respectively, for the neurogenic and inflammatory phases. The extract was
      ineffective when assessed in the hot-plate assay. In serotonin-induced paw edema,
      G1 led to a maximal inhibition (MI) of 51.6 % after 120 min when administered I.
      P. and of 36 % after 15 min by the oral route ( O. R.). When the inflammatory
      agent was complete Freund's adjuvant, inhibition of paw edema was also observed
      after administration of the extract by both routes. In the capsaicin-induced ear
      edema the ID (50) values were 1.09 +/- 0.08 mg/kg ( I. P.) and 10.00 +/- 0.90
      mg/kg ( O. R.). In the acute carrageenan-induced inflammatory reaction induced by
      carrageenan, G1 reduced the number of neutrophils in the peritoneal cavity with
      IC (50) values of 0.72 +/- 0.08 mg/kg and 4.17 +/- 0.50 mg/kg, by I. P. or O. R.
      administration, with a preferential migration of polymorphonuclear neutrophils.
      IN VITRO, G1 decreased nitric oxide production in LPS-stimulated RAW 264.7 cells
      (IC (50) = 41.60 microg/mL), and also the luciferase activity in TNF-alpha
      stimulated HEK 293 cells transfected with NF-kappaB-luciferase reporter gene
      driven by the nuclear factor kappaB (NF-kappaB) (IC (50) = 200 microg/mL). This
      extract, which at low concentrations induces anti-inflammatory and analgesic
      effects in mouse models, presents a high content of flavonoids, known to inhibit
      inducible NOS (iNOS) activity. These data taken together led us to reinforce the
      hypothesis in the literature that the anti-inflammatory effect of propolis may be
      a due to inhibition of iNOS gene expression, through interference with NF-kappaB
      sites in the iNOS promoter.

PMID- 16902859
TI  - Prenylated xanthones as potential antiplasmodial substances.
AB  - Mangostin, the major xanthone of Garcinia mangostana, and a series of synthetic
      derivatives were investigated for their in vitro antiplasmodial activity against
      Plasmodium falciparum. Mangostin itself showed moderate activity, but prenylated
      xanthones containing alkylamino functional groups exhibited quite potent
      antiplasmodial activity. Some structure-activity relationships are proposed.

PMID- 16902860
TI  - Post-genome research on the biosynthesis of ergot alkaloids.
AB  - Genome sequencing provides new opportunities and challenges for identifying genes
      for the biosynthesis of secondary metabolites. A putative biosynthetic gene
      cluster of fumigaclavine C, an ergot alkaloid of the clavine type, was identified
      in the genome sequence of ASPERGILLUS FUMIGATUS by a bioinformatic approach. This
      cluster spans 22 kb of genomic DNA and comprises at least 11 open reading frames
      (ORFs). Seven of them are orthologous to genes from the biosynthetic gene cluster
      of ergot alkaloids in CLAVICEPS PURPUREA. Experimental evidence of the identified
      cluster was provided by heterologous expression and biochemical characterization
      of two ORFs, FgaPT1 and FgaPT2, in the cluster of A. FUMIGATUS, which show
      remarkable similarities to dimethylallyltryptophan synthase from C. PURPUREA and
      function as prenyltransferases. FgaPT2 converts L-tryptophan to
      dimethylallyltryptophan and thereby catalyzes the first step of ergot alkaloid
      biosynthesis, whilst FgaPT1 catalyzes the last step of the fumigaclavine C
      biosynthesis, i. e., the prenylation of fumigaclavine A at C-2 position of the
      indole nucleus. In addition to information obtained from the gene cluster of
      ergot alkaloids from C. PURPUREA, the identification of the biosynthetic gene
      cluster of fumigaclavine C in A. FUMIGATUS opens an alternative way to study the
      biosynthesis of ergot alkaloids in fungi.

PMID- 16902862
TI  - The effect of cicerfuran, an arylbenzofuran from Cicer bijugum, and related
      benzofurans and stilbenes on Leishmania aethiopica, L. tropica and L. major.
AB  - The effect of 3 arylbenzofurans and 7 stilbenes on the growth of Leishmania
      parasites and human monocytes was evaluated. Promastigotes from cultures of L.
      aethiopica, L. major and L. tropica were tested in the exponential phase of
      growth. All compounds were active at concentrations of 100 microg/mL within 6
      hours. The 2-hydroxylstibene showed activity at a concentration < 1 microg/mL,
      with an LD (50) of 3 - 5 microg/mL after 48 hours of incubation. The most active
      compounds: cicerfuran, 2-hydroxy-2'-methyl-4',5'-methylenedioxystilbene, 2
      hydroxy-2'-methoxy-4',5'-methylenedioxystilbene and 2-hydroxystilbene had even
      stronger activity against the temperature-induced amastigotes of L. aethiopica,
      with the latter having the highest relative potency against all three species.
      Leishmanicidal activity seemed to be associated with the level of oxygen
      substitution in each compound. The ratio between leishmanicidal activity on
      promastigotes and toxicity to human cells suggested that the compounds could be
      considered as leishmanicidal drug leads.

PMID- 16902865
TI  - Diterpenes from "Pini Resina" and their preferential cytotoxic activity under
      nutrient-deprived condition.
AB  - In the course of our search for anticancer agents based on a novel anti-austerity
      strategy, we found that the 70 % EtOH extract of "Pini Resina" showed 100 %
      preferential cytotoxicity at the concentration of 50 microg/mL. Further bioassay
      guided fractionation and purification led to the isolation of 15 compounds
      including one new compound 7-oxo-13 alpha-hydroxyabiet-8(14)-en-18-oic acid (1).
      Their structures were elucidated on the basis of spectroscopic analysis. Among
      the isolated compounds, methyl abieta-8,11,13-trien-18-oate (7) showed the most
      potent preferential cytotoxicity at 10 microg/mL under nutrient-deprived
      condition.

PMID- 16902863
TI  - Tetramethylpyrazine attenuates adriamycin-induced apoptotic injury in rat renal
      tubular cells NRK-52E.
AB  - Tetramethylpyrazine (TMP), a compound purified from Rhizoma Ligustici, is a
      widely used active ingredient in Chinese herbal medicine to treat cardiovascular
      diseases on account of its vasodilatory actions and antiplatelet activity.
      Studies have shown that TMP can remove oxygen free radicals and protect rat
      kidney from ischemia-reperfusion injury. In addition, adriamycin-induced
      nephrosis in rats is commonly used in pharmacological studies of human chronic
      renal diseases. Apoptosis of renal tubular cells has been reported in adriamycin
      treated rats. To examine the therapeutic potential of TMP on chronic progressive
      renal diseases, adriamycin-induced injury in rat renal tubular cells NRK-52E has
      been used to monitor its protective effect. In TUNEL staining, TMP showed a dose
      dependent protective effect against adriamycin-induced apoptosis in NRK-52E
      cells. Pretreatment of the cells with 10 or 100 microM of TMP effectively
      decreased the reactive oxygen species (ROS) formation induced by adriamycin, as
      measured in fluorescent assays. TMP was found to reduce the adriamycin-stimulated
      activities of caspase-3, caspase-8 and caspase-9, inhibit adriamycin-induced
      release of cytochrome C, and elevate the expression of Bcl-x (L). TMP was also
      able to inhibit the death receptor signaling pathway and suppress the activation
      of transcription factor NF-kappaB in adriamycin-treated NRK-52E cells. Based on
      the results of this study, we suggest that TMP can attenuate adriamycin-induced
      oxidative stress and apoptotic injury in NRK-52E cells, and that it may have
      therapeutic potential for patients with renal diseases. TMP: tetramethylpyrazine
      LDH: lactate dehydrogenase ROS: reactive oxygen species DCF: 2',7'
      dichlorofluorescein TNF-alpha: tumor necrosis factor-alpha TUNEL: terminal
      deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end
      labeling.

PMID- 16902867
TI  - Growth inhibitory activity of wood of Taxus yunnanensis and its liquid
      chromatography Fourier-transform mass spectrometry analysis.
AB  - The wood of Taxus yunnanensis (Taxaceae) showed growth inhibitory activities
      against human cancer cell lines, such as cervical HeLa adenocarcinoma. The
      morphological changes indicated that the cellular growth inhibitions were caused
      by apoptosis. To determine the active components, T. yunnanensis wood was
      analyzed by using a liquid chromatography-Fourier-transform MS (LC/FT-MS)
      technique. As a result, taxane-type diterpenes, such as 10-deacetylcephalomannine
      and 10-deacetyltaxol, were found to be present in amounts consistent with the
      growth inhibitory activity.

PMID- 16902869
TI  - Stability of andrographolide in powdered Andrographis herb under accelerated
      conditions.
AB  - The stability of andrographolide in powdered Andrographis Herb--the aerial part
      of Andrographis paniculata (Burm. f.) Nees (Acanthaceae)--was determined using a
      heat-accelerated experiment to reveal a second-order kinetics of degradation. The
      fast decomposition was observed regardless of the method of analysis. The rate
      constant of the decomposition of andrographolide at 25 degrees C ( K(25)( degrees
      C)), predicted from the Arrhenius plot, was 6.58 x 10 (-6) d (-1).

PMID- 16902870
TI  - Enhancement of the fungicidal activity of amphotericin B by allicin, an allyl
      sulfur compound from garlic, against the yeast Saccharomyces cerevisiae as a
      model system.
AB  - Amphotericin B (AmB) is a representative antibiotic for the control of serious
      fungal infections, and its fungicidal activity was greatly enhanced by allicin,
      an allyl-sulfur compound from garlic. In addition to the plasma membrane
      permeability change, AmB induced vacuole membrane damage so that the organelles
      were visible as small discrete particles. Although allicin was ineffective in
      promoting AmB-induced plasma membrane disability, this compound enhanced AmB
      induced structural damage to the vacuolar membrane even at a non-lethal dose of
      the antibiotic. Allicin could also enhance the antifungal activity of AmB against
      the pathogenic fungus Candida albicans and against Aspergillus fumigatus. In
      contrast, allicin did not enhance the cytotoxic activity of AmB against cells of
      human promyelocytic leukemia (HL-60), a vacuole-less organism.

PMID- 16902871
TI  - Cytotoxic compounds of Schizolaena hystrix from the Madagascar rainforest.
AB  - Bioassay-guided fractionation of a crude ethanol extract from a Madagascar
      collection of Schizolaena hystrix afforded the two new long-chain compounds, 3 S
      acetoxyeicosanoic acid ethyl ester ( 1) and 3 S-acetoxydoeicosanoic acid ( 2),
      and the known long-chain compound 3 S-acetoxyeicosanoic acid ( 3). In addition,
      the long-chain alcohol 1-hydroxydodecan-2-one ( 7), as well as the new flavonoid
      schizolaenone C ( 4) and the two known flavonoids diplacol ( 5) and 3'
      prenylnaringenin ( 6) were isolated from a methanol extract of the same plant.
      Isolation and structure elucidation of the novel compounds and the cytotoxicities
      of all the isolates are reported.

PMID- 16902872
TI  - A Chinese herbal decoction, Danggui Buxue Tang, prepared from Radix Astragali and
      Radix Angelicae Sinensis stimulates the immune responses.
AB  - Danggui Buxue Tang (DBT), a Chinese medicinal decoction that is used commonly for
      treating women's ailments, contains Radix Astragali and Radix Angelicae Sinensis.
      The ratio of Radix Astragali and Radix Angelicae Sinensis used in DBT should be 5
      : 1 as described in China in 1247 A.D. In order to verify the efficacy of this
      ancient formulation in stimulating the immune responses, DBT prepared from
      different drug ratios was applied onto cultured T-lymphocytes and macrophages. In
      cultured T-lymphocytes, DBT induced markedly cell proliferation, secretion of
      interleukin-2 and phosphorylation of extracellular signal-regulated kinase. In
      addition, the phagocytosis of cultured macrophages was increased by DBT
      treatment. The immunomodulatory effects of DBT were revealed to be the strongest
      in the extract derived from the drug ratio of 5 : 1. The current results verified
      that the ancient formulation of DBT has been optimized in stimulating immune
      responses.

PMID- 16902873
TI  - Bacillisporins D and E, new oxyphenalenone dimers from Talaromyces bacillisporus.
AB  - The oligophenalenone dimer duclauxin and two new analogues, bacillisporins D and
      E, were isolated from the fungus TALAROMYCES BACILLISPORUS in addition to the
      previously reported bacillisporins A, B and C. Structures were established by
      spectroscopic studies. Duclauxin and bacillisporins A, B, C and E were evaluated
      for cytotoxicity against three human cancer cell lines. Bacillisporin A was
      strongly active against MCF-7 and NCI-H460 and moderately active against SF-268
      while bacillisporins B, C and duclauxin were moderately active against all three
      cell lines.

PMID- 16902874
TI  - Topical negative pressure therapy in wounds after cardiothoracic surgery:
      successful experience supported by literature.
AB  - BACKGROUND: Patients undergoing cardiothoracic surgery are at substantial risk of
      developing surgical site infections (SSI). SSI is not only associated with an
      increased morbidity but also with high mortality. Topical negative pressure
      therapy (TNP) is a promising method for treating surgical site defects (SSD). In
      recent years, we have gained a wide experience with TNP in a great variety of
      SSD. METHODS: We completed a prospective follow-up report of all patients treated
      with TNP after cardiothoracic surgery at the Academic Medical Centre Amsterdam, a
      university hospital. A review of the current evidence for TNP in cardiothoracic
      surgery is presented. RESULTS: Between August 2000 and March 2005, TNP was used
      in 105 patients in 113 SSD. As we gained more experience, we saw a decline in
      hospital stay ( P < 0.0001) and duration of TNP therapy. Surgical closure was
      performed in 62 % of patients using simple surgical (reconstructive) techniques.
      Therapy-related complications were rare (n = 1). CONCLUSION: Based on clinical
      findings and supported by the research presented, the treatment modality of
      choice for SSD after cardiothoracic surgery is TNP.

PMID- 16902875
TI  - Long-term results of surgical treatment of tetralogy of Fallot in adults.
AB  - BACKGROUND: The long-term results of patients with tetralogy of Fallot surgically
      treated in adulthood were evaluated to define the real benefit of surgical
      correction. METHODS: Between August 1990 and February 2004, 57 patients older
      than 18 years of age with tetralogy of Fallot received total correction. Forty
      two patients (73.7 %) required transannular patch. RESULTS: Hospital and late
      mortality were 7.0 % (n = 4) and 5.7 % (n = 3), respectively. One patient was
      reoperated on to close residual ventricular septal defect. Four patients were
      lost. Of the remaining 49 patients, the mean follow-up was 65 +/- 38 months
      (range 11 - 173 months). Actuarial survival was 97.4 +/- 2.5 %, 91 +/- 7 % and
      72.8 +/- 17.1 % at 5, 10 and 14 years, respectively. At the latest follow-up, 35
      (76.1 %) of the surviving patients presently have NYHA functional class I ( P <
      0.01). CONCLUSION: The overall survival of surgically treated adult patients with
      tetralogy of Fallot is acceptable. The greatest benefit of total correction at
      this age is the functional improvement.

PMID- 16902876
TI  - Prediction of and risk factors for surgical wound infection in the saphenous vein
      harvesting leg in patients undergoing coronary artery bypass.
AB  - BACKGROUND: Surgical wound infection (SWI) of the leg after saphenous vein
      harvesting is an important complication of coronary artery bypass graft (CABG)
      procedures. SWIs may restrict mobility in the postoperative period and increase
      costs of postoperative hospitalisation and antibiotic treatment. METHODS: A total
      of 356 patients were followed. Surgical risk factors were evaluated for SWI
      following saphenous vein harvesting, and the effectiveness of an occlusive
      glycerinated hydrogel dressing in reducing postoperative SWIs was assessed. In
      addition, the ability of postoperative clinical wound assessment to predict SWI
      following CABG 30 and 60 days after operation was investigated. RESULTS: The most
      important risk factor for SWI after saphenous vein harvesting was the use of a
      monofilament suture for skin closure (glycomer 4-0 Biosyn Tyco Healthcare,
      Stockholm, Sweden) (p > 0.001). The hydrogel dressing did not prevent the
      development of SWIs. The clinical wound assessment showed that wound gap was
      associated with leg infection, but other signs were poor predictors of SWI.
      CONCLUSION: The choice of suture and suturing technique is important to prevent
      SWI following saphenous vein harvesting. More precise definitions of wound signs
      are necessary if they are to be used as predictors of SWI.

PMID- 16902877
TI  - Diabetes mellitus increases adverse neurocognitive outcome after coronary artery
      bypass grafting surgery.
AB  - BACKGROUND: Cognitive dysfunction is a well known problem in the postoperative
      period in cardiac surgery. We hypothesised that the incidence of postoperative
      cognitive dysfunction in patients with diabetes mellitus is higher than in the
      nondiabetic patient. METHODS: Thirty-four patients (11 females, 23 males) with a
      mean age of 62.44 +/- 7.52 undergoing on-pump CABG surgery were studied in a
      prospective manner. Fourteen patients had treated diabetes mellitus (Group I) and
      20 were nondiabetic (Group II). All patients were operated upon by the same
      surgeon under standardised intra- and perioperative conditions. Patients with
      preoperative dementia (MMSE < 24) or advanced cerebrovascular disease were
      excluded. An extensive set of tests examining emotional and cognitive state,
      stress-coping and quality of life were performed preoperatively. Emotional and
      cognitive variables were assessed daily from day two to five postoperatively.
      RESULTS: All tests showed comparable results between the groups preoperatively.
      The perfusion lasted considerably longer in Group I (102.5 +/- 16.61 vs. 83.9 +/-
      14.1 min) as did the cross clamping (64.21 +/- 18.31 vs. 51.75 +/- 10.88 min).
      Postoperative cognitive outcome was significantly worse in Group I with regard to
      the Stroop Test (29.46 +/- 8.6 vs. 24.01 +/- 6.23, P = 0.02), the Abbreviated
      Mental Test (8.04 +/- 0.71 vs. 8.68 +/- 0.78, P = 0.02) and the Trial Making Test
      (35.72 +/- 11.38 vs. 29.3 +/- 7.77 P = 0.04). These differences persisted even
      after adjustment for perfusion- and cross-clamping time. CONCLUSION: The
      cognitive outcome in the early postoperative period is worse in diabetic patients
      compared to nondiabetics. Speed-related cognitive functions are mainly affected.
      Probably, this reflects a different physiology of cerebral perfusion during
      extracorporeal circulation. Optimising perfusion strategies to improve the
      outcome of diabetic patients should be the next topic of study.

PMID- 16902878
TI  - The controversy of donor serum sodium levels in heart transplantation--a
      multicenter experience.
AB  - BACKGROUND: Elevated donor serum sodium is a phenomenon often encountered in the
      management of brain dead donors. The clinical relevance on recipient outcome is
      less examined. We investigated the impact of elevated donor serum sodium levels
      (DSL) on outcome after heart transplantation in 1800 heart transplantations.
      METHODS: Data was conducted in a retrospective analysis from 1989 until 2005. The
      transplantations were performed at three German heart transplant centers. The
      joined database included DSL at the time of organ procurement, recipient and
      donor age, ischemia time, primary graft failure and survival data. RESULTS: Mean
      DSL was 147.7 +/- 10.3 l/l (range 111 - 208 l/l). Recipients were divided into 4
      groups with percentiles of 141, 147, and 154 l/l resulting in DSL of A: 135.8 +/-
      4.4, B: 143.6 +/- 1.7, C: 149.7 +/- 1.9, and D: 161.3 +/- 7.7 l/l for the four
      quartiles. Primary graft failure occurred in 2.6 % of the patients with A: 2.8 %,
      B: 2.8 %, C: 3.7% and D: 1.4 % ( P = n.s.). Mean 5- and 10-year-survival rates
      were 70.9 % (57.6 %) with A: 71.1 % (53.86 %), B: 69.3 % (53.9 %), C: 72.7 %
      (61.0 %), D: 71.2 % (62.4 %), respectively ( P = n. s.). In a multivariate
      analysis a significant impact on postoperative results could be revealed for
      recipient age ( P = 0.002), ischemia time ( P = 0.002) and donor age ( P =
      0.009). DSL were no individual risk factor in the multivariate analysis.
      CONCLUSION: There was no impact of donor serum sodium levels neither on early
      postoperative results, nor on long-term outcome indicating that cardiac
      allografts from donors with elevated sodium levels might be transplanted
      successfully, achieving favourable results.

PMID- 16902879
TI  - The Na+/H+ exchange inhibitor cariporide is washed out of the myocardium by
      crystalloid cardioplegia.
AB  - BACKGROUND: Inhibition of the Na (+)/H (+) exchanger (NHE) is cardioprotective,
      but dosage and timing of NHE-inhibitors are critical for their efficacy. We
      studied the effect of a new dosing regime of the NHE-inhibitor cariporide on
      myocardial function and damage after cardioplegic arrest (CPA) and determined its
      myocardial and serum concentrations. METHODS: 3 pigs received a bolus of 180 mg
      cariporide intravenously (i. v.) and were sacrificed shortly thereafter to allow
      measurement of the myocardial concentrations of cariporide. Subsequently, 10 pigs
      were randomized to receive either i. v. cariporide (bolus followed by an infusion
      of 40 mg/h) or placebo. Cardiopulmonary bypass was initiated, and the heart was
      arrested for 60 minutes by infusion of St. Thomas Hospital solution. Left
      ventricular (LV) function was studied using microsonometry. Myocardial damage was
      assessed by troponin T. Serum concentrations of cariporide were measured
      throughout the study, and myocardial concentrations were measured before the end
      of CPA and 180 minutes thereafter. RESULTS: Cariporide was present in all
      myocardial specimens (median: 1.4 ng/mg) studied previously. In the main study,
      LV function or myocardial damage did not differ significantly between the groups
      at any time point. Stable serum cariporide concentrations were achieved (3.4 +/-
      0.5 microg/ml). Cariporide was detectable in only one of the myocardial biopsies
      obtained before the end of CPA, but 180 minutes thereafter, the myocardial
      cariporide concentration was 2.5 +/- 0.3 ng/mg. CONCLUSION: We observed no effect
      of i. v. cariporide on LV function or myocardial damage after cardioplegic
      arrest. Our data suggest that cariporide is washed out of the myocardium by
      repeated application of crystalloid cardioplegia. Thus, the mode of delivery also
      appears to be critical for cardioprotection with NHE-inhibitors.

PMID- 16902880
TI  - Blunt and penetrating traumatic ruptures of the diaphragm.
AB  - BACKGROUND: The difficulties in diagnosing traumatic diaphragmatic rupture (TDR)
      at the first admission are the most common causes of morbidity and mortality. The
      purpose of this study was to review our experience with the management of TDR in
      order to identify the factors contributing to diagnostic delay and associated
      morbidity and mortality. METHODS: Fourteen patients with TDR were treated in our
      hospital between January 2000 and June 2005. They have been investigated
      retrospectively. RESULTS: The study identified 9 men (64 %) and 5 women (36 %),
      with ages ranging from 19 to 65 years (mean 35.3 years). Rupture of the diaphragm
      was left-sided in 10 (71 %) and right-sided in 4 (29 %) of the patients. Blunt
      trauma accounted for the injuries of 11 patients (79 %). Early diagnosis was
      obtained in 9 patients (64 %). The diagnosis was established preoperatively in 8
      patients (57 %), and intraoperatively in 4 (29 %). The diagnosis was missed in 2
      (14 %) patients in the first operation. Multiple associated injuries were
      observed in 12 patients (85 %). Postoperative complications were encountered in
      five patients (35 %), and the overall mortality was 7 %. CONCLUSIONS:
      Diaphragmatic rupture should be suspected in all blunt or penetrating traumas of
      the thorax and abdomen, and the presence of such an injury should be excluded
      before terminating the exploratory procedure.

PMID- 16902881
TI  - Multimodal treatment of osteosarcoma lung metastases.
AB  - OBJECTIVE: The diagnostic procedures, role of surgery and multimodal treatment
      for osteosarcoma pulmonary metastases are examined. METHODS: From January 2000 to
      June 2005, we observed 35 patients with osteogenic repetitions. Patients were
      studied by total-body computerised tomography (CT) and by thoracic single-photon
      emission computerised tomography (SPECT). Preoperative histological diagnosis was
      obtained by CT-guided transthoracic needle biopsy (23 cases) and fibre-optic
      bronchoscopy (12 cases). RESULTS: Four lower, 6 upper and 2 middle lobectomies
      were carried out using a thoracotomy approach. Video-assisted thoracoscopy was
      used in the other 23 patients who underwent 36 wedge resections. CT showed a
      sensitivity of 86 % and a specificity of 66 %; SPECT had a sensitivity of 80 %
      and a specificity of 100 %. Twenty-five patients are still living 25 +/- 11
      months after the intervention. CONCLUSIONS: SPECT was demonstrated to offer a
      better result in the individualisation of secondary pulmonary nodules after
      primary osteosarcoma. The excision of all resectable lung metastases, integrated
      in a multidisciplinary strategy, offers good results in terms of survival.

PMID- 16902882
TI  - Malignant pleural effusion treatment outcomes: pleurodesis via video-assisted
      thoracic surgery (VATS) versus tube thoracostomy.
AB  - STUDY OBJECTIVES: Video-assisted thoracic surgery (VATS) has been widely used in
      the diagnosis and management of various thoracic diseases. The objective of this
      retrospective study was to compare the effectiveness of patients undergoing
      pleurodesis through VATS versus tube thoracostomy for malignant pleural effusion
      (MPE). Study design was a retrospective review of patients treated in medical
      centers and hospitals in Taiwan. PATIENTS: One hundred and forty-eight patients
      with MPE resistant to systemic therapy resulting from various types of carcinomas
      were retrospectively reviewed. VATS pleurodesis was carried out in 82 and tube
      thoracostomy with pleurodesis in 66 patients. RESULTS: There were no
      intraoperative deaths and 4 (2.7 %) in-hospital deaths. One hundred and eighteen
      (79.7 %) patients were available for follow-up. There were no statistically
      significant differences in the preoperative characteristics of the two treatment
      groups, except that the amount of effusion and the percentage of patients with
      dyspnea were both higher in the VATS treatment group. The duration of chest tube
      drainage was significantly longer ( P < 0.01) in the tube thoracostomy treatment
      group (9.1 +/- 3.3 vs. 6.2 +/- 2.3 days). There were no significant differences
      between the treatment groups with regard to the incidence of surgical
      complications and perioperative mortality. Median survival was similar in both
      treatment groups; however, the VATS treatment group had a significantly longer
      median recurrence-free survival than the tube thoracostomy treatment group.
      CONCLUSIONS: VATS treatment for MPE appears to be superior to tube thoracostomy
      for diagnostic accuracy and effectiveness in preventing effusion recurrence;
      however, the role of these treatments for MPE is palliative, and does not
      significantly prolong survival time.

PMID- 16902883
TI  - Less vigorous surgery for second primary lung cancer.
AB  - BACKGROUND: Patients with second primary lung cancer (SPLC) have a heterogeneous
      background. The optimum modality of treatment for SPLC patients has not yet been
      determined. The objective of this study was to attempt to identify the value of
      less vigorous therapies such as segmentectomy or video-assisted thoracic surgery
      (VATS) in SPLC. METHODS: We retrospectively reviewed the medical records of 46
      patients who underwent resection for SPLC in Fukuoka University Hospital between
      January 1994 and April 2005. Patients were separated into two groups (LVT: less
      vigorous therapy including segmentectomy or VATS lobectomy; LCT: lobectomy with
      conventional thoracotomy). The characteristics of each group were evaluated and
      survival rates were analyzed at 5 years after surgery. RESULTS: The mean amount
      of blood loss was found to be significantly different ( P = 0.0062) with 59.44 +/
      14.00 ml for LVT cases and 254.48 +/- 63.62 ml for LCT. None of the LVT patients
      experienced postoperative complications. The 5-year survival rate was 62.7 % for
      LVT and 57.7 % for LCT. There was no significant difference in survival rates
      between these groups. CONCLUSIONS: Although differences were seen in the
      characteristics, less invasive surgery such as VATS or segmentectomy may be a
      feasible treatment for SPLC.

PMID- 16902884
TI  - Cardiopulmonary effects of intravenous prostaglandin E1 during experimental one
      lung ventilation.
AB  - BACKGROUND: One-lung ventilation greatly improves operating conditions during
      thoracic surgery. Serious disadvantages of one-lung ventilation are hypoxaemia
      and increased pulmonary vascular resistance. Prostaglandins, like prostaglandin
      I2 (PGI2), are potent pulmonary vasodilators but may also influence venous
      admixture and systemic circulation. Since the lung is capable of extensive
      degradation of prostaglandin E1 (PGE1) but not of PGI2, PGE1 might affect
      systemic circulation to a lesser degree. Hence, we studied the effects of
      intravenous PGE1 on systemic and pulmonary circulation and on oxygenation during
      one-lung ventilation. METHODS: Lateral thoracotomy and cross-clamping of the left
      main stem bronchus was performed in twelve anaesthetised and ventilated pigs.
      Animals were cannulated with arterial, central venous and fast response
      thermodilution pulmonary artery catheters for haemodynamic measurements. PGE1 was
      administered with infusion rates of 25, 50, and 100 ng x kg (-1) x min (-1)
      during one-lung ventilation. RESULTS: All doses of PGE1 significantly decreased
      pulmonary vascular resistance and mean pulmonary artery pressure. However, a
      comparable significant reduction in systemic vascular resistance and mean
      arterial pressure was found. Arterial oxygen tension and venous admixture showed
      a slight but significant deterioration. Oxygen delivery remained unchanged or
      increased since the cardiac index increased. CONCLUSION: During one-lung
      ventilation in the pig, infusion of PGE1 significantly decreased pulmonary
      vascular resistance and pulmonary artery pressure but failed to achieve selective
      pulmonary vasodilation.

PMID- 16902885
TI  - Pulmonary sclerosing hemangioma with pulmonary metastasis.
AB  - We present a case of pulmonary sclerosing hemangioma with multiple involvements.
      Pulmonary sclerosing hemangioma is a relatively rare neoplasm. Although it is
      thought to be benign, cases with lymph node metastasis or multiple pulmonary
      involvement have been reported in clinical settings. To date, no case has been
      reported with mortality due to sclerosing hemangioma, however its clinical
      characteristics of multiple spread and lymphnode metastasis have not yet been
      elucidated.

PMID- 16902886
TI  - Giant aneurysm of left anterior descending coronary artery treated by surgical
      off-pump therapy.
AB  - Coronary artery aneurysms may predispose to acute thrombosis, embolisation and
      myocardial ischaemia or rupture with subsequent tamponade and/or sudden death.
      The optimal therapy for patients with coronary artery aneurysm is unknown, and
      controversy persists regarding the use of medical or surgical modalities. There
      is no doubt that surgical therapy is reserved for cases with large aneurysms or
      with myocardial ischaemia due to significant associated coronary artery stenoses.
      We discuss here the surgical management of a case with coronary artery aneurysm
      and concomitant coronary artery disease. Although the beating heart technique of
      myocardial revascularisation and repair of coronary artery aneurysm without
      cardiopulmonary bypass is not suitable for all patients, it should be considered
      for those high-risk patients who have impaired left ventricular function or who
      are at high risk for pulmonary or neurological complications.

PMID- 16902887
TI  - Fracture of Colvin-Galloway-Future band in a patient with mitral valve
      annuloplasty.
AB  - Annuloplasty with various annuloplasty ring systems is a fundamental part of
      mitral valve repair and has been frequently performed since its introduction by
      Carpentier in 1969. Due to the different advantages or disadvantages of each
      system, some controversies exist regarding the best type of ring annuloplasty
      support. Here we describe, for the first time, the case of a female patient in
      which a fracture of a semi-rigid open annuloplasty ring occurred, leading to
      annular deformation and mitral regurgitation.

PMID- 16902888
TI  - An aspergilloma in an echinococcal cyst cavity.
AB  - Aspergilloma is a saprophytic infection which can colonize preexisting lung
      cavities. The most common underlying diseases are tuberculosis, sarcoidosis,
      cavitary lung cancer, etc. Although aspergilloma can also occur in operated
      hydatid cyst cavities, only a few cases have been reported in literature. A 32
      year-old female patient underwent cystectomy for the diagnosis of perforated
      intraparenchymal giant hydatid cyst located in the right upper lobe, reaching
      down to the hilum. Capitonnage was not performed and it was observed that a
      residual cavity remained in the cystectomy area. The patient was discharged;
      however, during clinical and radiological follow-ups, it was found that the
      residual cyst cavity had expanded. As it was thought that one of the drainage
      bronchi in the cyst cavity could have opened, the patient was reoperated. During
      the operation, it was noted that purulent fluid and necrotic tissues were present
      in the cystic cavity. It was seen that the posterior upper lobe segment was
      consolidated and not ventilated. Contents of the cavity were removed and the
      posterior upper lobe segment was resected. Histopathological examination revealed
      that the tissue in the cavity was that of an aspergilloma, and that chronic
      organized pneumonia and diffuse interstitial fibrosis were present in the
      resected segment. Refraining from surgical obliteration (capitonnage) of cyst
      cavities in cases of giant hydatid cysts extending to the hilum can lead to
      opportunistic infections such as aspergilloma.

PMID- 16902889
TI  - Cardiac lipoma in the ventricular septum--a case report.
AB  - We report a case of a cardiac lipoma in the interventricular septum complicated
      with mitral regurgitation and atrial fibrillation in a 74-year-old woman.
      Surgical excision of the tumor was performed with mitral annuloplasty and a Maze
      III procedure. She continues to do well 7 months postoperatively.

PMID- 16902890
TI  - Revascularisation of a giant coronary artery aneurysm in suspected incomplete
      Kawasaki-disease.
AB  - Kawasaki disease leads to typical vascular complications in up to 20 % of
      untreated cases. We describe a 47-year-old patient with coronary vessel disease,
      involving the right coronary artery with a huge aneurysmatic dilatation,
      suspicious for an incomplete form of Kawasaki disease. We found little
      information about the surgical treatment and postoperative course of this disease
      in adults. Typically, these infrequent patients present with acute myocardial
      infarction and require interdisciplinary decision-making.

PMID- 16902891
TI  - [Revision of guidelines for the management of patients with congenital heart
      failure in Germany].
AB  - The German Society for Thoracic and Cardiovascular Surgery (GSTCVS) regards 250
      operations on patients with congenital heart disease per institution as an
      optimal number (Thorac Cardiov Surg 2006; 54: 73 - 77). In addition, all German
      institutions ought to participate unequivocally on data transfer to the European
      Association for Cardiothoracic Surgery. However, these "optimal German
      structures" need to be translated into action now. It will have to be the GSTCVS
      to ask for a hearing at the Federal Joint Committee (G-BA) (www.g-ba.de). This
      medical self-governing body, formed from the national associations of doctors and
      dentists, the German Hospital Federation and the health insurance funds, gives
      concrete definition to the legal requirements and implements them. Recently, the
      Federal Joint Committee released concrete measures for the care of newborns
      (Press release 21. 9. 2005, section sign 91 Abs. 7 SGB V). The obvious thing to
      do now would be considering measures for care of patients with congenital heart
      disease. We conclude, that whereas treatment and results should be further
      improved by quality control and quality transparency, structures of institutions
      involved in the care of patients with congenital heart disease can only be
      implemented by the Federal Joint Committee.

PMID- 16902892
TI  - Cardiac surgery in Germany during 2005: a report on behalf of the German Society
      for Thoracic and Cardiovascular Surgery.
AB  - All cardiac surgical procedures performed in 79 German cardiac surgical units
      throughout the year 2005 are presented in this report, based on a voluntary
      registry, which is organized by the German Society for Thoracic and
      Cardiovascular Surgery. In 2005, a total of 98 860 cardiac surgical procedures
      (ICD and pacemaker procedures excluded) were collected in this registry. More
      than 8.4 % of the patients were older than 80 years, compared to 7.8 % in 2004.
      Hospital mortality in 54 126 isolated CABG procedures (9.7 % off-pump) was 2.9 %,
      while a mortality of 4.5 % was observed in 19 203 isolated valve procedures. This
      registry is an important tool of the German Society for Thoracic and
      Cardiovascular Surgery to ensure a continuous and voluntary quality assurance and
      illustrate the development of cardiac surgery in Germany.

PMID- 16902893
TI  - [Preisdent's editorial, 2006].

PMID- 16902894
TI  - [Local excision with transanal endoscopic microsurgery (TEM) after endoscopic
      R1/R2-polypectomy of pT1 "low-risk" carcinomas of the rectum].
AB  - The transanal endoscopic microsurgery (TEM) is an adequate method for the local
      full-thickness excision of large rectum polyps and pT1 "low-risk" rectal
      carcinomas. We studied prospectively the relevance of this surgical technique
      concerning complete tumour excision after R1/R2-polypectomy of malignant rectal
      polyps. 16 patients with pT1 "low-risk" rectal carcinoma and macroscopic (R2) or
      microscopic (R1) incomplete endoscopic polypectomy were locally resected by TEM.
      In 12 patients (75 %) no residual tumour was found. In the remaining four cases
      (25 %), one adenoma with high-grade atypia, two pT1 "low-risk" carcinomas and one
      tumour infiltration in the mesorectal fat were diagnosed. The patient with the
      mesorectal infiltration was immediately operated on with radical resection. No
      further tumour cells were found in this specimen. The median follow-up was 21
      months. One patient with a pT1 "low-risk" carcinoma developed a local recurrence
      and a single hepatic metastasis in the left liver lobe after TEM. Both were
      completely resected. Currently, all patients are living without evidence of
      tumour recurrence. Transanal endoscopic microsurgery is a suitable method for the
      treatment of pT1 "low-risk" rectal carcinomas after incomplete endoscopic
      polypectomy. In cases of a "high-risk" tumour or deeper tumour infiltration (pT>
      1) after TEM radical resection must be carried out.

PMID- 16902895
TI  - [Probiotic drug therapy with E. coli strain Nissle 1917 (EcN): results of a
      prospective study of the records of 3,807 patients].
AB  - INTRODUCTION: Living microorganisms that enter the gut in an active state and
      exert a positive influence on the host are called probiotics. Numerous
      experimental and clinical studies were performed recently and confirm both the
      efficacy and modes of action of probiotic drugs. PATIENTS AND METHODS: In a post
      marketing-surveillance study with the probiotic Escherichia Coli strain Nissle
      1917 (EcN) data on the range of indications as well as on efficacy and tolerance
      were gathered prospectively in 446 centres. The intended treatment duration was
      limited to a maximum of 12 weeks. RESULTS: EcN was used in 3,807 patients with
      more than 20 different indications, n = 3,511 of whom had gastrointestinal
      complaints: Among others, 1,067 patients presented with chronically recurring (n
      = 728) or protracted diarrhoea (n = 339), 415 with inflammatory bowel disease,
      679 with irritable bowel syndrome, and 253 with chronic constipation. The overall
      efficacy was assessed as good to very good by an average of 81.4 % of the
      therapists. The stool frequency and consistency as well as the symptoms of
      meteorism and abdominal pain were improved in very many patients. Suspected cases
      of side effects were documented in only 2.8 % of the patients. CONCLUSION: EcN is
      frequently used in practice for the treatment of various, mostly
      gastrointestinal, complaints and is well tolerated.

PMID- 16902896
TI  - [Listeria meningitis in a patient with Crohn's disease--a seldom, but clinically
      relevant adverse event of therapy with infliximab].
AB  - A 42-year-old man with steroid-dependent Crohn's disease developed fever,
      vomiting and headache after the second administration of infliximab. Extensive
      microbiological and biochemical work-up revealed an atypical meningitis caused by
      Listeria monocytogenes. After antibiotic therapy of 21 days duration, the patient
      could be discharged from hospital totally recovered without any further
      complications. As previously demonstrated, TNF-alpha plays an important role in
      resistance to Listeria monocytogenes. Listeria infections have been reported in
      26 patients receiving TNF-alpha inhibitors. An additional therapy with other
      immunosuppressants increases the risk for Listeria infections. Listeria
      meningitis is a seldom adverse event of therapy with TNF-alpha inhibitors but is
      associated with a high lethality. Therefore patients should be informed about the
      possible adverse event of a Listeria infection during anti-TNF-alpha therapy
      before receiving immunosuppressive treatment. Furthermore, therapy with TNF-alpha
      inhibitors should only be executed within a close doctor-patient relationship and
      in cooperation with specialised centres.

PMID- 16902897
TI  - [Dieulafoy's lesion of the right hemicolon].
AB  - Dieulafoy's lesion was described in 1896 by the French pathologist Georges D.
      Dieulafoy as a vascular malformation in the stomach. Although usually found in
      the stomach, the lesion may occur anywhere within the gastrointestinal tract and
      can cause severe hemorrhage. There is no sex or age predilection. The diagnosis
      is established endoscopically, and the current therapy of choice is endoscopic
      hemoclipping. Only rarely is the diagnosis confirmed histologically. We report
      the case of an elderly female patient who, while hospitalised for a slipped
      intervertebral disc, presented with lower gastrointestinal bleeding. The source
      of the bleeding was suspected to be in the right colon by endoscopy. Renewed
      massive bleeding necessitated surgical treatment with resection of the right
      hemicolon. The histological work-up of the resected specimen identified a 350
      micron large tortuous submucosal artery that had eroded.

PMID- 16902898
TI  - Pathophysiology in Microvillus inclusion disease.
AB  - Microvillus inclusion disease (MID) is a congenital disorder with the clinical
      signs of watery diarrhea often beginning in the first days of life. The main
      pathological features of the disease include a villus atrophy and an accumulation
      of periodic acid-Schiff (PAS)-positive material within the apical cytoplasm of
      enterocytes on the light microscopy level. Electron microscopic criteria are
      pathognomonic consisting of an increased amount of secretory granules
      preferentially in crypt epithelial cells and of the presence of microvillus
      inclusion bodies (MIBs) which are most frequently found in villus enterocytes.
      Until now the basic molecular defects have not been disclosed completely. In this
      review we discuss the actual pathogenetic hypothesis and the therapeutic options
      besides small bowel transplantation.

PMID- 16902900
TI  - [Endoscopic anti reflux treatment--unhappy ending or start of a new era?].

PMID- 16902899
TI  - [Immunotherapy of colorectal cancer--overview and perspectives].
AB  - The specific immunotherapy of colorectal cancer initially revealed promising
      results. However, a significant clinical benefit for patients has still to be
      proven in phase III trails. In order to compare the different clinical approaches
      and early phase I - II studies, there is an urgent need for the establishment and
      acceptance of new standardized diagnostic tools for detecting and quantifying
      induced and clinical relevant immune responses in patients. Whether or not
      subgroups with a certain genetic background, such as specific HLA alleles, reveal
      a better benefit from tumour vaccinations needs to be further analysed.
      Currently, only two specific antibodies, targeting membraneous receptors or their
      ligands, such as EGF or VEGF, have been approved by diverse national drug
      authorities. The question as to whether these antibodies also induce an antibody
      dependent cellular toxicity (ADCC) is currently being analysed.

PMID- 16902901
TI  - [Effectiveness of inpatient pulmonary rehabilitation (AHB). Results of a
      multicenter prospective observation study].
AB  - BACKGROUND AND OBJECTIVE: The value of pulmonary rehabilitation in the treatment
      of chronic obstructive pulmonary disease (COPD) is well accepted. However, there
      are no data on the efficacy of in-patient rehabilitation instituted within 14
      days after an acute disease episode, as practised in Germany. It was the purpose
      of this multi-centre prospective study to assess changes in lung function,
      exercise capacity, symptoms and disease-related quality of life (QoL) in patients
      discharged from hospital for an episode of worsening COPD or asthma, pulmonary
      embolism, pneumonia or treatment of lung cancer. PATIENTS AND METHODS: 207
      patients (mean age 60 13 years) with COPD (n=86), pneumonia (n=42), lung cancer
      (n=24), asthma (n=14), pulmonary embolism (n=7) or other pulmonary disease (n=34)
      were included. Measurements of lung function, exercise capacity and disease
      related QoL were carried out at the beginning and end of rehabilitation. Socio
      economic data and disease-related QoL measurements were recorded again after 2
      months. RESULTS: Rehabilitation led to a significant improvement of lung
      function, exercise capacity and QoL. Patients felt rehabilitation was efficacious
      (95%), to be recommended (99%) and important (100%). Improvement of QoL was
      maintained at two 2 months and only 16% of previously working patients had
      applied for retirement. CONCLUSIONS: The data demonstrate the clinically relevant
      benefit of in-patient pulmonary rehabilitation immediately after a period of
      acute illness. In view of these result and the known morbidity and mortality of
      patients with COPD after hospitalization for a period of acute illness, this form
      of pulmonary rehabilitation should be considered as standard treatment for these
      patients.

PMID- 16902902
TI  - [Achalasia in circumscribed scleroderma].
AB  - HISTORY: A 38-year-old man had been suffering from circumscribed scleroderma for
      12 years. Dysphagia had been diagnosed 5 years ago and for the last 2 years he
      had retrosternal dysphagia for solid and liquid food. His symptoms had increased
      markedly 6 months before presenting at our hospital and the patient had lost 15
      kg of weight. 2 months ago, a percutaneous endoscopic gastrostomy (PEG) had been
      inserted at another hospital. INVESTIGATIONS: The patient presented in a reduced
      general and nutritional state. The routine laboratory tests and tumor markers
      were within normal range. Endoscopy showed a moderately dilated esophagus with
      food remnants. It was not possible to pass the cardia without exerting pressure.
      Esophageal manometry and barium upper gastrointestinal series revealed the
      classical findings of achalasia. THERAPY AND COURSE: An extramucosal Heller
      myotomy with anterior semifundoplication (Dor's procedure) was performed. The
      postoperative course was uneventful and the patient was able to take solid and
      liquid food without any dysphagia. CONCLUSION: The association of achalasia and
      circumscribed scleroderma has not been described in medical publications yet. The
      entity could possibly be based on common autoimmune mechanisms and an analogous
      pathogenesis with resulting fibrosis.

PMID- 16902903
TI  - [Chronic anaemia in a patient with hereditary haemorrhagic telangiectasia and
      juvenile gastric polyposis].
AB  - HISTORY: A 52-year-old woman with chronic anaemia presented with recurrent
      epistaxis, telangiectasias and haemangiomas, suggesting the presence of
      hereditary haemorrhagic telangiectasia (Osler-Rendu-Weber disease). Moreover,
      previous investigations had also shown multiple polyps of the stomach.
      INVESTIGATIONS: A severe microcytic iron deficiency anaemia in combination with
      hepatic haemangiomas and duodenal angio-dysplasia were detected. Gastrointestinal
      endoscopy revealed multiple juvenile polyps in the gastric fundus and body,
      indicating the diagnosis of hereditary haemorrhagic telangiectasia in combination
      with juvenile polyposis. THERAPY AND COURSE: A gastrectomy was performed because
      of recurrent gastrointestinal bleeding and the malignant potential of juvenile
      gastric polyposis. Histopathology confirmed the diagnosis and did not reveal any
      malignancy. CONCLUSION: The association of hereditary haemorrhagic telangiectasia
      and juvenile polyposis, as seen in this patient, has been reported repeatedly. A
      diagnosis of one of the described entities should initiate the screening for
      evidence of the other one to prevent (life-threatening) complications.

PMID- 16902904
TI  - [Lipohypertrophy].

PMID- 16902905
TI  - [Identification of tumor antigens: strategies and perspectives].

PMID- 16902906
TI  - [Contrast agents in transabdominal ultrasonography: state of the art and
      perspectives].

PMID- 16902907
TI  - [Surgical treatment of carotid artery stenosis: still indicated today? Current
      indications and future requirements--a review].

PMID- 16902909
TI  - [Development of various forms of hypertension and a new assessment of
      antihypertensive medication].

PMID- 16902910
TI  - [Hematothorax after sudden chest pain].

PMID- 16902911
TI  - [Persistent CK-elevation after CSE inhibitor therapy].

PMID- 16902916
TI  - Helicobacter: the ease and difficulty of a new discovery (Nobel lecture).

PMID- 16902913
TI  - Relationship between point gene mutation, chromosomal abnormality, and tumour
      suppressor gene methylation status in colorectal adenomas.
AB  - Epigenetic mechanisms in carcinogenesis may have a significant role in the
      development of colorectal cancer. To investigate this phenomenon in early-stage
      disease, promoter methylation status in the tumour suppressor genes APC, MGMT,
      hMLH1, P14/P14ARF, and CDKN2A/P16 was investigated in 78 colorectal adenomas.
      These had previously been characterized for mutations of APC, KRAS, and TP53
      genes and for chromosomal abnormality by comparative genomic hybridization (CGH).
      APC hypermethylation was seen in 52 tumours (66.7%). APC showed either
      methylation or mutation in 66 lesions (84.6%), but these events were not
      statistically associated. MGMT methylation was detected in 39 cases (50%).
      Adenomas with this abnormality showed a significantly lower number of chromosomal
      changes by CGH (p < 0.02), confirming that DNA repair defect of this type is
      associated with a lower level of chromosomal instability. An hMLH1 methylation
      defect was seen in only one adenoma (1.3%), from a patient who had a synchronous
      cancer showing the same defect. Methylation of P14 (P14ARF) was seen in 31
      adenomas (39.7%) and CDKN2A (P16) abnormality in 25 (32.1%). DNA methylation at
      two or more loci was seen in 46 tumours (59%), while 11 lesions (14.1%) showed no
      evidence of hypermethylation at any of the loci studied. Methylation at any or
      all of MGMT, P14 or P16 was significantly associated with APC methylation (p =
      0.01). Those neoplasms with more than two methylated genes showed significantly
      fewer chromosomal abnormalities than adenomas with one or no methylated loci (p <
      0.001). There was no association between specific individual chromosomal
      abnormalities, APC, KRAS or TP53 mutations and any pattern of methylation
      abnormality. We conclude that methylation abnormality is very common in pre
      invasive colorectal neoplasia, and that high level methylation is associated with
      low level chromosomal instability.

PMID- 16902917
TI  - Inhibition of TNF-alpha signaling: divide and conquer.

PMID- 16902918
TI  - Medicinal chemistry optimization of acyldepsipeptides of the enopeptin class
      antibiotics.

PMID- 16902919
TI  - Evaluation and binding-mode prediction of thiopyrone-based inhibitors of anthrax
      lethal factor.

PMID- 16902920
TI  - Protease-mediated phototoxicity of a polylysine-chlorin(E6) conjugate.

PMID- 16902921
TI  - Characterization of solid counterfeit drug samples by desorption electrospray
      ionization and direct-analysis-in-real-time coupled to time-of-flight mass
      spectrometry.

PMID- 16902922
TI  - The discovery of CCR5 receptor antagonists for the treatment of HIV infection:
      hit-to-lead studies.

PMID- 16902923
TI  - Derivatives of 3-sec-butyl-1-oxo-2,3-dihydroisoquinoline as inhibitors of mu
      calpain.

PMID- 16902924
TI  - The synthesis and testing of arenearylpyrimidylmethanes as antimalarial agents.

PMID- 16902925
TI  - Influence of the scyphostatin side chain on the mode of inhibition of neutral
      sphingomyelinase.

PMID- 16902926
TI  - Chiral recognition of D-kyotorphin by lipidic membranes: relevance toward
      improved analgesic efficiency.
AB  - D-Kyotorphin (D-KTP), the most potent isomer of the endorphin-like dipeptide
      kyotorphin (KTP), is a good drug candidate for the treatment of chronic pain and
      is thought to be involved in receptor-mediated processes. According to the
      "membrane catalysis" model, ligands interact with membrane lipids to attain high
      local concentrations in the receptor vicinity and to adopt the necessary
      conformation for docking. Therefore, the interaction and recognition of D-KTP by
      membranes is potentially important to its increased analgesic effect. In spite of
      the neutral net charge of D-KTP at pH 7.4, fluorescence spectroscopy reveals that
      the interaction with large unilamellar vesicles is more extensive than was
      observed for KTP. The tyrosine residue interacts extensively with rigid
      membranes, with a location and well-defined orientation in the bilayer. This
      suggests not only that D-KTP meets the structural constraints needed for receptor
      ligand interaction in a manner similar to that of KTP, but also that the stronger
      membrane interaction and ability to discriminate rigid membrane domains might
      contribute to its improved analgesic effect.

PMID- 16902927
TI  - Synthesis and biological evaluation of boronic acid containing cis-stilbenes as
      apoptotic tubulin polymerization inhibitors.
AB  - A series of boronic acid containing cis-stilbenes as potent inhibitors of tubulin
      polymerization was synthesized by the introduction of boronic acid as an acceptor
      type functional group into the aromatic ring B of the combretastatin framework.
      High cell-growth inhibition was observed with boron compounds 13 c and 13 d, in
      which a hydroxy group on the aromatic ring B of combretastatin A-4 was replaced
      with boronic acid; IC50 values toward B-16 and 1-87 cell lines are 0.48-2.1
      microM. Compounds 13 c and 13 d exhibited significant inhibitory activity toward
      tubulin polymerization (IC50=21-22 microM). The carboxylic acid derivative 17,
      which can be considered as a mimic of boronic acid 13 c, did not show significant
      inhibition of cell growth or tubulin polymerization. According to the FACScan
      analysis using Jurkat cells, apoptosis was induced after incubation for 8 h with
      13 c at a concentration of >10(-8) M. Growth inhibitory experiments against a
      panel of 39 human cancer cell lines revealed 13 c to inhibit growth differently
      than combretastatin A-4; the correlation coefficient (r) between the two
      compounds was 0.553 in the COMPARE analysis.

PMID- 16902930
TI  - The 7 TM G-protein-coupled receptor target family.
AB  - Chemical biology approaches have a long history in the exploration of the G
      protein-coupled receptor (GPCR) family, which represents the largest and most
      important group of targets for therapeutics. The analysis of the human genome
      revealed a significant number of new members with unknown physiological function
      which are today the focus of many reverse pharmacology drug-discovery programs.
      As the seven hydrophobic transmembrane segments are a defining common structural
      feature of these receptors, and as signaling through heterotrimeric G proteins is
      not demonstrated in all cases, these proteins are also referred to as seven
      transmembrane (7 TM) or serpentine receptors. This review summarizes important
      historic milestones of GPCR research, from the beginning, when pharmacology was
      mainly descriptive, to the age of modern molecular biology, with the cloning of
      the first receptor and now the availability of the entire human GPCR repertoire
      at the sequence and protein level. It shows how GPCR-directed drug discovery was
      initially based on the careful testing of a few specifically made chemical
      compounds and is today pursued with modern drug-discovery approaches, including
      combinatorial library design, structural biology, molecular informatics, and
      advanced screening technologies for the identification of new compounds that
      activate or inhibit GPCRs specifically. Such compounds, in conjunction with other
      new technologies, allow us to study the role of receptors in physiology and
      medicine, and will hopefully result in novel therapies. We also outline how basic
      research on the signaling and regulatory mechanisms of GPCRs is advancing,
      leading to the discovery of new GPCR-interacting proteins and thus opening new
      perspectives for drug development. Practical examples from GPCR expression
      studies, HTS (high-throughput screening), and the design of monoamine-related
      GPCR-focused combinatorial libraries illustrate ongoing GPCR chemical biology
      research. Finally, we outline future progress that may relate today's discoveries
      to the development of new medicines.

PMID- 16902931
TI  - Helicobacter connections.
AB  - After preliminary studies in 1981, Marshall and Warren conducted a study in which
      the new bacterium Helicobacter pylori was cultured. In that series, 100 % of 13
      patients with duodenal ulcer were found to be infected. The hypothesis that
      peptic ulcer was caused by a bacterial infection was not accepted without a
      fight. Most experts believed that Helicobacter was a harmless commensal,
      infecting people who had ulcers for some other reason. In response, Marshall
      drank a culture of Helicobacter to prove that the bacteria could infect a healthy
      person and cause gastritis. The truth behind peptic ulcers was revealed; that is,
      very young children acquired the Helicobacter organism, leading to a chronic
      infection which caused a lifelong susceptibility to peptic ulcers. Marshall
      developed new treatments for the infection and diagnostic tests which allowed the
      hypothesis to be evaluated and proven. After 1994 Helicobacter was generally
      accepted as the cause of most gastroduodenal diseases including peptic ulcer and
      gastric cancer. As a result of this knowledge, treatment is a simple procedure,
      and stomach surgery has become a rarity.

PMID- 16902932
TI  - GR ligands: can we improve the established drugs?

PMID- 16902933
TI  - Design, synthesis, and in vivo efficacy of glycine transporter-1 (GlyT1)
      inhibitors derived from a series of [4-phenyl-1-(propylsulfonyl)piperidin-4
      yl]methyl benzamides.

PMID- 16902934
TI  - Synthesis and activity of carbazole derivatives against Mycobacterium
      tuberculosis.

PMID- 16902935
TI  - Permeability of phospholipid vesicles to the tumor antigen epitope gp100(280
      288).

PMID- 16902936
TI  - In situ polymerized hydrogels for repairing scleral incisions used in pars plana
      vitrectomy procedures.

PMID- 16902937
TI  - Automated protein-ligand crystallography for structure-based drug design.
AB  - An approach to automate protein-ligand crystallography is presented, with the aim
      of increasing the number of structures available to structure-based drug design.
      The methods we propose deal with the automatic interpretation of diffraction data
      for targets with known protein structures, and provide easy access to the
      results. Central to the system is a novel procedure that fully automates the
      placement of ligands into electron density maps. Automation provides an objective
      way to structure solution, whereas manual placement can be rather subjective,
      especially for data of low to medium resolution. Ligands are placed by docking
      into electron density, whilst taking care of protein-ligand interactions. The
      ligand fitting procedure has been validated on both public domain and in-house
      examples. Some of the latter deal with cocktails of low-molecular weight
      compounds, as used in fragment-based drug discovery by crystallography. For such
      library-screening experiments we show that the method can automatically identify
      which of the compounds from a cocktail is bound.

PMID- 16902938
TI  - Integrated approach using protein and ligand information to analyze selectivity-
      and affinity-determining features of carbonic anhydrase isozymes.
AB  - The application and comparison of selected protein- and ligand-based approaches
      to elucidate factors important for affinity and selectivity towards the carbonic
      anhydrase isozymes I, II, and IV are described. Carbonic anhydrases are abundant
      in pro- and eukaryotes. These enzymes catalyze the reversible hydration of carbon
      dioxide to bicarbonate and H(+) ions and are thus involved in many important
      physiological and pathophysiological processes. Due to the fact that the human
      carbonic anhydrase family consists of 16 closely related isozymes, the design of
      selective inhibitors is a special challenge for medicinal chemists. In order to
      extract selectivity-determining features, we applied purely ligand-based 3D QSAR
      techniques as well as qualitative comparative molecular field analyses of the
      targets' binding sites using consensus principal component analysis (CPCA). The
      dataset for the QSAR studies was deliberately compiled from 1,748 inhibitors and
      comprises about 140 ligands, mainly of the sulfonamide type. Additionally, we
      employed the novel AFMoC approach, which intrinsically combines protein and
      ligand information. The simultaneous use of these different techniques gives
      deeper insight into selectivity and affinity-determining features and provides
      quantitative models for prediction.

PMID- 16902939
TI  - FlexNovo: structure-based searching in large fragment spaces.
AB  - We present a new molecular design program, FlexNovo, for structure-based
      searching within large fragment spaces following a sequential growth strategy.
      The fragment spaces consist of several thousands of chemical fragments and a
      corresponding set of rules that specify how the fragments can be connected.
      FlexNovo is based on the FlexX molecular docking software and makes use of its
      incremental construction algorithm and the underlying chemical models.
      Interaction energies are calculated by using standard scoring functions. Several
      placement geometry, physicochemical property (drug-likeness), and diversity
      filter criteria are directly integrated into the "build-up" process. FlexNovo has
      been used to design potential inhibitors for four targets of pharmaceutical
      interest (dihydrofolate reductase, cyclin-dependant kinase 2, cyclooxygenase-2,
      and the estrogen receptor). We have carried out calculations using different
      diversity parameters for each of these targets and generated solution sets
      containing up to 50 molecules. The compounds obtained show that FlexNovo is able
      to generate a diverse set of reasonable molecules with drug-like properties. The
      results, including an automated similarity analysis with the Feature Tree
      program, indicate that FlexNovo often reproduces structural motifs as well as the
      corresponding binding modes seen in known active structures.

PMID- 16902940
TI  - Phosphopeptide ligands of the SHP-1 N-SH2 domain: effects on binding and
      stimulation of phosphatase activity.
AB  - Src homology 2 (SH2)-domain-mediated interactions with phosphotyrosine (pY)
      containing ligands are critical for the regulation of SHP-1 phosphatase activity.
      Peptides based on a binding site from receptor tyrosine kinase Ros (EGLN-pY2267
      MVL, 1) have recently been shown to bind to the SHP-1 N-terminal SH2 domain (N
      SH2) with considerably high affinity. In addition, two peptides cyclized between
      positions -1 and +2 relative to pY (EGLc[K(COCH(2)NH)pYMX]L-NH(2), 2: X=D, 3:
      X=E) bound to the N-SH2 domain, but did not activate the enzyme and even
      partially prevented stimulation of SHP-1 activity by the physiological ligand 1.
      These findings prompted us to further examine the determinants for optimal
      binding to the N-SH2 domain and for the stimulation and inhibition of SHP-1
      activity. Herein we demonstrate that combining the preferred residues in both
      pY+1 (such as Phe or norleucine, Nle) and pY+3 (such as homophenylalanine, Hfe)
      leads to highly efficient activating ligands of SHP-1. Particularly in the
      context of the cyclic peptides 7 (EGLc[K(COCH(2)NH)pYFD]Hfe-NH(2)) and 8
      (EGLc[K(COCH(2)NH)pYNleD]HfeL-NH(2)), the incorporation of these residues
      resulted in high-affinity ligands with a significantly increased ability to
      stimulate SHP-1 activity. We suggest that different binding modes (according to
      consensus sequences class I and II) are responsible for obtaining either
      activating (7 and 8) or nonactivating (2 and 3) ligands. Peptides such as 7 and 8
      that bind in the extended fashion of the type II mode activate the phosphatase
      through complete filling of the cavity for pY+3. In contrast, peptides such as 2
      and 3 that bind in the class I mode do not activate the enzyme because they allow
      more conformational space at pY+3. Therefore, their binding does not force the
      conformational transition necessary to trigger the dissociation of N-SH2 and the
      catalytic domain.

PMID- 16902941
TI  - The predicted 3D structures of the human M1 muscarinic acetylcholine receptor
      with agonist or antagonist bound.
AB  - The muscarinic acetylcholine G-protein-coupled receptors are implicated in
      diseases ranging from cognitive dysfunctions to smooth-muscle disorders. To
      provide a structural basis for drug design, we used the MembStruk computational
      method to predict the 3D structure of the human M1 muscarinic receptor. We
      validated this structure by using the HierDock method to predict the binding
      sites for three agonists and four antagonists. The intermolecular ligand-receptor
      contacts at the predicted binding sites agree well with deductions from available
      mutagenesis experiments, and the calculated relative binding energies correlate
      with measured binding affinities. The predicted binding site of all four
      antagonists is located between transmembrane (TM) helices 3, 4, 5, 6, and 7,
      whereas the three agonists prefer a site involving residues from TM3, TM6, and
      TM7. We find that Trp 157(4) contributes directly to antagonist binding, whereas
      Pro 159(4) provides an indirect conformational switch to position Trp 157(4) in
      the binding site (the number in parentheses indicates the TM helix). This
      explains the large decrease in ligand binding affinity and signaling efficacy by
      mutations of Trp 157(4) and Pro 159(4) not previously explained by homology
      models. We also found that Asp 105(3) and aromatic residues Tyr 381(6), Tyr
      404(7), and Tyr 408(7) are critical for binding the quaternary ammonium head
      group of the ligand through cation-pi interactions. For ligands with a charged
      tertiary amine head group, we suggest that proton transfer from the ligand to Asp
      105(3) occurs upon binding. Furthermore, we found that an extensive aromatic
      network involving Tyr 106(3), Trp 157(4), Phe 197(5), Trp 378(6), and Tyr 381(6)
      is important in stabilizing antagonist binding. For antagonists with two terminal
      phenyl rings, this aromatic network extends to Trp 164(4), Tyr 179(extracellular
      loop 2), and Phe 390(6) located at the extracellular end of the TMs. We find that
      Asn 382(6) forms hydrogen bonds with selected antagonists. Tyr381(6) and Ser
      109(3) form hydrogen bonds with the ester moiety of acetylcholine, which binds in
      the gauche conformation.

PMID- 16902942
TI  - Improving potency, selectivity, and water solubility of adenosine A1 receptor
      antagonists: xanthines modified at position 3 and related pyrimido[1,2,3
      cd]purinediones.
AB  - The structure-activity relationships of xanthine derivatives related to the
      adenosine A(1) receptor antagonists 8-cyclopentyl-1,3-dipropylxanthine (DPCPX)
      and 1,3-dipropyl-8-(3-noradamantyl)xanthine (KW3902) were investigated by
      focusing on variations of the 3-substituent. Aromatic residues were well
      tolerated by the A(1) receptor in that position. A moderate effect of
      stereochemistry was found for the 3-(1-phenylethyl)-substituted analogue of DPCPX
      (S>R) at A(1) and A(3) receptors, whereas the opposite stereoselectivity was
      observed at the A(2) receptor subtypes. A 3-hydroxypropyl substituent was found
      to be optimal for high A(1) affinity and selectivity. The most potent compound of
      the present series was 1-butyl-3-(3-hydroxypropyl)-8-(3-noradamantyl)xanthine (10
      c), which exhibits a K(i) value of 0.124 nM at rat, and 0.7 nM at human adenosine
      A(1) receptors, combined with high selectivity (>>200-fold) versus the other
      receptor subtypes. The similarly potent 8-cyclopentyl-3-(3-hydroxypropyl)-1
      propylxanthine was converted into a water-soluble phosphate prodrug, which may
      become a useful pharmacological tool for in vivo studies. 8-Alkyl-2-(3
      noradamantyl)pyrimido[1,2,3-cd]purine-8,10-diones, which can be envisaged as
      xanthine analogues with a fixed 3-propyl substituent, were identified as a new
      class of potent, selective adenosine A(1) receptor antagonists. For example,
      compound 14 (8-butyl-substituted) exhibits a K(i) value of 13.8 nM at human A(1)
      receptors. A selection of the most potent compounds was investigated in
      [(35)S]GTPgammaS binding assays and showed inverse agonistic activity. Their
      efficacy was generally lower than that of the full inverse agonist DPCPX, and
      depended on subtle structural changes. Some of the new compounds belong to the
      most potent and selective A(1) antagonists described to date.

PMID- 16902944
TI  - Pharmacokinetic changes of ipriflavone in rats with acute renal failure induced
      by uranyl nitrate.
AB  - Pharmacokinetic parameters of ipriflavone were compared after intravenous (20
      mg/kg) and oral (200 mg/kg) administration in control rats and in rats with acute
      renal failure induced by uranyl nitrate (U-ARF rats). It was expected that the
      time-averaged nonrenal clearance (Cl(nr)) of ipriflavone in U-ARF rats could be
      significantly slower than in the control rats, since it was reported that
      ipriflavone was metabolized via the hepatic microsomal cytochrome P450 (CYP)
      1A1/2 and 2C11 and the expression and mRNA level of CYP1A2 were not changed, but
      those of CYP2C11 were decreased in U-ARF rats compared with control rats.
      Unexpectedly, after intravenous administration in U-ARF rats, the Cl(nr) of
      ipriflavone was significantly faster than in the controls (40.8 compared with
      29.0 ml/min/kg). This may be due to an increase in the glucuronide conjugate
      formation of ipriflavone metabolites in U-ARF rats. After oral administration of
      ipriflavone in U-ARF rats, the AUC(0-24 h) was significantly smaller (194
      compared with 295 microg min/ml) than in the controls.

PMID- 16902945
TI  - Female gamete preservation.
AB  - The use of multiple agent chemotherapy and combined modality treatment of
      childhood and adolescent cancers has markedly increased survival rates. Thus, the
      majority of young cancer patients survive into adulthood and the potential long
      term consequences of the therapies are of ongoing concern. Alkylating agents have
      proven to be the most toxic to the ovaries; however radiation is also extremely
      gonadotoxic. In addition, combination of these modalities will produce additive
      effects in terms of ovarian damage (follicle depletion). As a result, there are
      increasing numbers of young cancer survivors with impaired or absent gonadal
      function. Advances in the field of assisted reproductive technology (ART) provide
      hope that the reproductive impact of cancer therapy can be reduced. Those
      technologies that may be applicable prior to gonadotoxic therapy are pretreatment
      ovarian protection with oral contraceptives or gonadotropin releasing hormone
      agonist; ART using pretreatment cryopreservation of embryos or gametes;
      posttreatment ART with donor gametes or embryos; or adoption. However, ovarian
      protection is not of proven benefit and oocyte/ovary cryopreservation has had
      only limited success to date. Information regarding cancer treatment's possible
      effects on fertility and ways to potentially circumvent these should be part of
      routine counseling to allow the patient to make an informed decision.

PMID- 16902946
TI  - Health-risk behaviors and health promotion in adolescent and young adult cancer
      survivors.
AB  - A diagnosis of cancer during adolescence, a period characterized by
      experimentation and risk-taking behaviors, has the potential to derail critical
      developmental tasks required for successful transition into adulthood. Health
      professionals caring for adolescents and young adults have an opportunity to
      influence behavioral practices by correcting knowledge deficits, addressing
      factors that enhance the survivor's sense of vulnerability to health problems,
      and providing personalized health counseling that encourages the practice of
      health promoting behaviors. The approach to health counseling in childhood cancer
      survivors should consider their unique educational needs related to their cancer
      experience. Previous investigations of adolescent and young adult survivor health
      behavior indicate that survivors perceive themselves as more vulnerable to health
      problems than their peers without cancer and recognize a need to protect their
      health. However, these perceptions of health vulnerability do not always
      correlate with health promoting behavioral practices, suggesting that factors
      other than health perceptions should be investigated to motivate behavioral
      change. Very few studies have been undertaken to prospectively evaluate the
      effectiveness of health promotion programs in adolescent and young adult
      survivors of cancer. The scarcity of knowledge in the issue of health promotion
      after childhood cancer underscores the need for more research to define 1) the
      optimal timing of health counseling; 2) the influence of developmental status and
      neurocognitive function; 3) the most effective methods and venues for health
      education; 4) the feasibility and cost-effectiveness of health promotion
      strategies; and 5) psychosocial and economic impediments to practice of healthy
      behaviors.

PMID- 16902948
TI  - One-pot synthesis of amino-alcohols using a de-novo transketolase and beta
      alanine: pyruvate transaminase pathway in Escherichia coli.
AB  - Biocatalysis continues to emerge as a powerful technique for the efficient
      synthesis of optically pure pharmaceuticals that are difficult to access via
      conventional chemistry. The power of biocatalysis can be enhanced if two or more
      reactions can be achieved by a single whole cell biocatalyst containing a pathway
      designed de-novo to facilitate a required synthetic sequence. The enzymes
      transketolase (TK) and transaminase (TAm) respectively catalyze asymmetric carbon
      -carbon bond formation and amine group addition to suitable substrate molecules.
      The ability of a transaminase to accept the product of the transketolase reaction
      can allow the two catalysts to be employed in series to create chiral amino
      alcohols from achiral substrates. As proof of principle, the beta-alanine:
      pyruvate aminotransferase (beta-A:P TAm) from Pseudomonas aeruginosa has been
      cloned, to create plasmid pQR428, for overexpression in E.coli strain
      BL21gold(DE3). Production of the beta-A:P TAm alongside the native transketolase
      (overexpressed from plasmid pQR411), in a single E.coli host, has created a novel
      biocatalyst capable of the synthesis of chiral amino alcohols via a synthetic two
      step pathway. The feasibility of using the biocatalyst has been demonstrated by
      the formation of a single diastereoisomer of 2-amino-1,3,4-butanetriol (ABT)
      product, in up to 21% mol/mol yield, by the beta-A:P TAm, via transamination of L
      erythrulose synthesized by TK, from achiral substrates glycolaldehyde (GA) and
      beta-hydroxypyruvate (beta-HPA). ABT synthesis was achieved in a one-pot process,
      using either whole cells of the dual plasmid strain or cell lysate, while the
      dual alcohol-amine functionality of ABT makes it an excellent synthon for many
      pharmaceutical syntheses.

PMID- 16902949
TI  - Differing mechanisms of cAMP- versus seawater-induced oocyte maturation in marine
      nemertean worms II. The roles of tyrosine kinases and phosphatases.
AB  - Instead of blocking oocyte maturation as it does in most animals, cAMP causes
      oocytes of marine nemertean worms to initiate maturation (=germinal vesicle
      breakdown, "GVBD"). To characterize cAMP-induced GVBD in nemerteans, inhibitors
      of tyrosine kinase signaling were tested on Cerebratulus sp. oocytes that had
      been incubated in cAMP-elevating drugs versus seawater (SW) alone. Such tests
      yielded similar results for Src-like tyrosine kinase blockers, as the inhibitors
      prevented mitogen-activated protein kinase (MAPK) activation without stopping
      either GVBD or maturation-promoting factor (MPF) activation in both SW and cAMP
      elevating treatments. Alternatively, genistein, a general tyrosine kinase
      antagonist, and piceatannol, an inhibitor of the tyrosine kinase Syk, reduced
      GVBD and MAPK/MPF activities in SW-, but not cAMP-induced maturation. Similarly,
      inhibitors of the human epidermal growth factor receptor-2 (HER-2) tyrosine
      kinase prevented GVBD and MAPK/MPF activations in oocytes treated with SW, but
      not with cAMP-elevating drugs. Antagonists of either protein tyrosine
      phosphatases (PTPs) or the dual-specificity phosphatase Cdc25 also reduced GVBD
      and MAPK/MPF activities in SW-treated oocytes without generally affecting cAMP
      induced maturation. Collectively, these data suggest cAMP triggers GVBD via
      pathways that do not require MAPK activation or several components of tyrosine
      kinase signaling. In addition, such differences in tyrosine kinase cascades,
      coupled with the dissimilar patterns of Ser/Thr kinase signaling described in the
      accompanying study, indicate that nemertean oocytes are capable of utilizing
      multiple mechanisms to activate MPF during GVBD.

PMID- 16902950
TI  - Contribution of comparative fish studies to general endocrinology: structure and
      function of some osmoregulatory hormones.
AB  - Fish endocrinologists are commonly motivated to pursue their research driven by
      their own interests in these aquatic animals. However, the data obtained in fish
      studies not only satisfy their own interests but often contribute more generally
      to the studies of other vertebrates, including mammals. The life of fishes is
      characterized by the aquatic habitat, which demands many physiological
      adjustments distinct from the terrestrial life. Among them, body fluid regulation
      is of particular importance as the body fluids are exposed to media of varying
      salinities only across the thin respiratory epithelia of the gills. Endocrine
      systems play pivotal roles in the homeostatic control of body fluid balance.
      Judging from the habitat-dependent control mechanisms, some osmoregulatory
      hormones of fish should have undergone functional and molecular evolution during
      the ecological transition to the terrestrial life. In fact, water-regulating
      hormones such as vasopressin are essential for survival on the land, whereas ion
      regulating hormones such as natriuretic peptides, guanylins and adrenomedullins
      are diversified and exhibit more critical functions in aquatic species. In this
      short review, we introduce some examples illustrating how comparative fish
      studies contribute to general endocrinology by taking advantage of such
      differences between fishes and tetrapods. In a functional context, fish studies
      often afford a deeper understanding of the essential actions of a hormone across
      vertebrate taxa. Using the natriuretic peptide family as an example, we suggest
      that more functional studies on fishes will bring similar rewards of
      understanding. At the molecular level, recent establishment of genome databases
      in fishes and mammals brings clues to the evolutionary history of hormone
      molecules via a comparative genomic approach. Because of the functional and
      molecular diversification of ion-regulating hormones in fishes, this approach
      sometimes leads to the discovery of new hormones in tetrapods as exemplified by
      adrenomedullin 2.

PMID- 16902951
TI  - Mode of action and functional significance of avian gonadotropin-inhibitory
      hormone (GnIH): a review.
AB  - Neuropeptide control of gonadotropin secretion at the level of the anterior
      pituitary gland is primarily through the stimulatory action of the hypothalamic
      decapeptide, gonadotropin-releasing hormone (GnRH). However, a hypothalamic
      neuropeptide acting at the level of the pituitary to negatively regulate
      gonadotropin secretion has, until recently, remained unknown in any vertebrate.
      In 2000, we discovered a novel hypothalamic neuropeptide inhibiting gonadotropin
      release at the level of the pituitary in quail and termed it gonadotropin
      inhibitory hormone (GnIH). A gonadotropin-inhibitory system is an intriguing
      concept and provides us with an unprecedented opportunity to study the regulation
      of avian reproduction from an entirely novel standpoint. To elucidate the mode of
      action of GnIH, we further identified the receptor for GnIH and characterized its
      expression and binding activity in quail. The identified GnIH receptor possessed
      seven transmembrane domains and specifically bound to GnIH in a concentration
      dependent manner. The expression of GnIH receptor was found in the pituitary and
      several brain regions including the hypothalamus. These results suggest that GnIH
      acts directly on the pituitary via GnIH receptor to inhibit gonadotropin release.
      GnIH may also act on the hypothalamus to inhibit GnRH release. To understand the
      functional significance of GnIH in avian reproduction, we also investigated the
      mechanism that regulates GnIH expression. Interestingly, melatonin induced dose
      dependently GnIH expression and melatonin receptor (Mel(1c)) was expressed in
      GnIH neurons. Thus melatonin appears to act directly on GnIH neurons via its
      receptor to induce GnIH expression. Based on these studies, GnIH is likely an
      important neuropeptide for the regulation of avian reproduction.

PMID- 16902952
TI  - Differing mechanisms of cAMP- versus seawater-induced oocyte maturation in marine
      nemertean worms I. The roles of serine/threonine kinases and phosphatases.
AB  - Unlike in most animals, oocytes of marine nemertean worms initiate maturation
      (=germinal vesicle breakdown, GVBD) following an increase, rather than a
      decrease, in intraoocytic cAMP. To analyze how serine/threonine (Ser/Thr) kinase
      cascades involving mitogen-activated protein kinase (MAPK), maturation-promoting
      factor (MPF), cAMP-dependent protein kinase (PKA), and phosphatidylinositol 3
      kinase (PI3K) regulate nemertean GVBD, oocytes of Cerebratulus sp. were treated
      with pharmacological modulators and stimulated with cAMP-elevating drugs or
      seawater (SW) alone. Both cAMP elevators and SW triggered GVBD while activating
      MAPK, its target p90Rsk, and MPF. Similarly, neither cAMP- nor SW-induced GVBD
      was affected by several Ser/Thr phosphatase inhibitors, and both stimuli
      apparently accelerated GVBD via a MAPK-independent, PI3K-dependent mechanism.
      However, inhibitors of Raf-1, a kinase that activates MAPK kinase, blocked GVBD
      and MAPK activation during SW-, but not cAMP-induced maturation. In addition, MPF
      blockers more effectively reduced GVBD and MAPK activity in SW versus in cAMP
      elevating treatments. Moreover, the two maturation-inducing stimuli yielded
      disparate patterns of PKA-related MAPK activations and phosphorylations of
      putative PKA substrates. Collectively, such findings suggest that in maturing
      oocytes of Cerebratulus sp., Ser/Thr kinase cascades differ during cAMP- versus
      SW-induced GVBD in several ways, including MAPK activation modes, MPF-feedback
      loops, and PKA-related signaling pathways. Additional differences in cAMP- versus
      SW-induced oocyte maturation are also described in the accompanying study that
      deals with the roles of tyrosine kinase signaling during GVBD.

PMID- 16902953
TI  - Transcriptome profiling of the tubular porcine conceptus identifies the
      differential regulation of growth and developmentally associated genes.
AB  - Gastrulation and trophectoderm elongation of the porcine conceptus coincide with
      peak conceptus estrogen secretion from gestational day 11 to day 12. The current
      study aim was to identify genes required for elongation by defining the
      transcriptome profile of this dynamic tubular stage. The gastrulation and
      proliferative status of ovoid, tubular, and filamentous conceptuses were also
      examined. Polarization of the embryonic disc and growth throughout the conceptus
      were evident. An unamplified and two distinct amplified serial analysis of gene
      expression (SAGE) libraries were generated from tubular conceptus mRNA. Comparing
      the three libraries at 12,000 tags/library indicated small-amplified RNA-SAGE was
      a reliable amplification procedure. The unamplified library was increased to
      42,415 tags and statistical analyses of tag frequencies with previously generated
      ovoid and filamentous libraries revealed the differential expression (P < 0.05)
      of 483 and 364 tags between ovoid:tubular or tubular:filamentous libraries,
      respectively. Annotated transcripts known to be involved in development and also
      potentially regulated by estrogen (cytokeratins 8 and 18, stratifin, midkine, and
      glycolytic enzymes) were further analyzed by real-time PCR. The majority of
      glycolytic enzyme transcripts were constitutively expressed or downregulated at
      the filamentous stage. Likewise, cytokeratin mRNAs were less abundant in
      filamentous conceptuses, whereas stratifin and midkine were more abundant in
      tubular conceptuses. Analysis of protein revealed distinct expression patterns
      for cytokeratin 18, stratifin, and midkine. The function(s) of these factors and
      potential modulation by estrogen clearly needs to be elucidated to understand
      their physiological role in normal conceptus development.

PMID- 16902954
TI  - Subzero water transport characteristics and optimal rates of freezing rhesus
      monkey (Macaca mulatta) ovarian tissue.
AB  - The purpose of the present study was to examine the effect of two different
      suprazero (room temperature +25 degrees C to +4 degrees C) cooling conditions on
      the measured water transport response of primate (Macaca mulatta) ovarian tissue
      in the presence and absence of cryoprotective agents (CPAs). Freshly collected
      Macaca mulatta (rhesus monkey) ovarian tissue sections were cooled at either 0.5
      degrees C/min or 40 degrees C/min from 25 to 4 degrees C. A shape independent
      differential scanning calorimeter (DSC) technique was then used to measure the
      volumetric shrinkage during freezing of ovarian tissue sections at a freezing
      rate of 5 degrees C/min in the presence and absence of three different CPAs (0.85
      M glycerol, 0.85 M dimethylsulfoxide, and 0.85 M ethylene glycol). Thus, water
      transport during freezing of primate ovarian tissue was obtained at eight
      different conditions (i.e., at four different freezing media with two different
      suprazero cooling conditions). The water transport response of ovarian tissue
      cooled rapidly from 25 to 4 degrees C was significantly different (P < 0.01) than
      that of slow cooled tissue, in the freezing media without CPAs and with
      dimethylsulfoxide. However, the differences in the measured water transport
      response due to the imposed suprazero cooling conditions were reduced with the
      addition of glycerol and ethylene glycol (statistically different with P < 0.05).
      By fitting a model of water transport to the experimentally obtained volumetric
      shrinkage data the best-fit membrane permeability parameters (L(pg) and E(Lp))
      were determined. The best-fit parameters of water transport in primate ovarian
      tissue sections ranged from: L(pg) = 0.7 to 0.15 microm/min-atm and E(Lp) = 22.1
      to 32.1 kcal/mol (the goodness of fit parameter, R(2) > 0.96). These parameters
      suggest that the "optimal rates of cryopreservation" for ovarian tissue are
      significantly dependent upon suprazero cooling conditions and the choice of CPA.

PMID- 16902955
TI  - Effects of hyaluronan, BSA, and serum on bovine embryo in vitro development,
      ultrastructure, and gene expression patterns.
AB  - Effects of hyaluronan (HA), BSA, and FCS on in vitro development, ultrastructure,
      and mRNA transcription of four developmentally important genes: apoptosis (Bax),
      oxidative stress (SOX), growth factor (IGF-II), and cell-to-cell adhesion (Ecad)
      were examined. Two biological origin HA, Hylartil and Hyonate and one produced by
      fermentation (f-HA) MAP-5 were tested. Embryos were cultured in SOF medium with
      0.4% BSA or with 0.4% BSA and 10% FCS. HA was added 96 hr post insemination (pi)
      to half of the embryos from each culture group. Embryo development was not
      affected by either HA preparation, however, hatching rates were higher in
      Hyalartil and MAP-5 than in control and Hyonate (P < 0.05). There was no effect
      of HA on number of blastocysts developed in SOF + BSA. However, more blastocysts
      developed in SOF + BSA + f-HA than in SOF + BSA + FCS or with BSA + FCS + f-HA.
      HA added to SOF + BSA, increased level of expression of epidermal growth factor
      (EGF)-II and decreased the levels of expression of BAX, SOX, and Ecad (P < 0.05).
      Presence of FCS increased the levels of SOX and decreased the level of IGF-II (P
      < 0.05) and the addition of f-HA to SOF containing FCS showed no effect on the
      level of transcription of any analyzed genes. The fine structure of embryos
      cultured with f-HA irrespective of protein sources used was clearly improved. In
      summary, f-HA added 96 hr pi to SOF supplemented with BSA but not FCS improved
      development, molecular composition and fine structure of bovine embryos.

PMID- 16902956
TI  - A comparison of high cell density fed-batch fermentations involving both induced
      and non-induced recombinant Escherichia coli under well-mixed small-scale and
      simulated poorly mixed large-scale conditions.
AB  - In this work, multi-parameter flow cytometric techniques, coupled with dual
      colour fluorescent staining, have been used to study the metabolic consequences
      of inclusion body formation in high cell density fed-batch cultures of the
      recombinant E. coli strain MSD3735, producing the IPTG inducible model mammalian
      protein, AP50. Further, we report on the development of the scale-down, two
      compartment (STR + PFR) experimental simulation model to study, for the first
      time, the effect of a changing microenvironment with respect to three of the
      major spatial heterogeneities that may be associated with large-scale
      bioprocessing (pH, glucose and dissolved oxygen concentration) on a recombinant
      bacterial system. Using various time points for induction and various scale-down
      configurations, it has been shown that inclusion body formation is followed
      immediately by a detrimental progressive change in individual cell physiological
      state with respect to both cytoplasmic membrane polarisation and permeability,
      resulting in a lower final biomass yield. However, the extent of this change was
      found to be dependent on whether the AP50 protein was induced or not, on the time
      of induction and on which combination of heterogeneities was being simulated.
      From this and previous work, it is clear that the scale-down two-compartment
      model can be used to study the impact of genetically modifying an organism to
      produce inclusion bodies and any range and combination of potential
      heterogeneities known to exist at the large scale.

PMID- 16902957
TI  - Comparative genomics in vertebrate evolution and development.
AB  - The vast quantities of publicly available DNA sequencing data and genome
      resources are enabling biologists to investigate age-old problems in biology that
      were not addressable previously. In this review, we discuss how comparative
      genomics is practiced and how the data can be used to make biological inferences
      with respect to vertebrate evolution and development. Examples are taken from the
      well-known HOX clusters, which are always a high-priority target for genomic
      analyses due to their inferred role in the evolution of metazoans. In addition,
      we briefly discuss the application of genomic approaches to problems in
      comparative endocrinology.

PMID- 16902958
TI  - Patterns and mechanisms of genome organization in the mouse.
AB  - The physical and functional organizations of a genome are correlated outcomes of
      evolution. Inbred strains of mice provide a unique opportunity for exploring
      these relationships, representing as they do, diverse genomes originally
      separated by millions of generations that were then scrambled in the laboratory
      and subjected to intense selection during inbreeding to homozygosity. Here we
      show that the resulting pattern of chromosome organization includes regional
      domains of functionally related elements that promote the co-inheritance and
      survival of compatible sets of alleles. There are also patterns of linkage
      disequilibrium between domains on separate chromosomes; these are distinctly non
      random and form networks with scale-free architecture. The strong conservation of
      gene order among mammals suggests that the domains and networks we find likely
      characterize all mammals, and possibly beyond.

PMID- 16902960
TI  - Neurosteroid biosynthesis in the quail brain: a review.
AB  - The brain traditionally has been considered to be a target site of peripheral
      steroid hormones. In contrast to this classical concept, new findings over the
      past decade have shown that the brain itself also has the capability of forming
      steroids de novo, the so-called "neurosteroids". De novo neurosteroidogenesis in
      the brain from cholesterol is a conserved property of vertebrates. Our studies
      using the quail, as an excellent animal model, have demonstrated that the avian
      brain possesses cytochrome P450 side-chain cleavage enzyme (P450scc), 3beta
      hydroxysteroid dehydrogenase/Delta(5)-Delta(4)-isomerase (3beta-HSD), cytochrome
      P450 17alpha-hydroxylase/c17,20-lyase (P450(17alpha,lyase)), 17beta-HSD, etc.,
      and produces pregnenolone, progesterone, 3beta, 5beta-tetrahydroprogesterone,
      androstenedione, testosterone and estradiol from cholesterol. However, the
      biosynthetic pathway of neurosteroids in the avian brain from cholesterol may be
      still incomplete, because we recently found that the quail brain actively
      produces 7alpha-hydroxypregnenolone, a previously undescribed avian neurosteroid.
      This paper summarize the advances made in our understanding of biosynthesis of
      neurosteroids in the avian brain.

PMID- 16902959
TI  - Xenobiotic detoxification in the nematode Caenorhabditis elegans.
AB  - The nematode Caenorhabditis elegans is an important model organism for the study
      of such diverse aspects of animal physiology and behavior as embryonic
      development, chemoreception, and the genetic control of lifespan. Yet, even
      though the entire genome sequence of this organism was deposited into public
      databases several years ago, little is known about xenobiotic metabolism in C.
      elegans. In part, the paucity of detoxification information may be due to the
      plush life enjoyed by nematodes raised in the laboratory. In the wild, however,
      these animals experience a much greater array of chemical assaults. Living in the
      interstitial water of the soil, populations of C. elegans exhibit a boom and bust
      lifestyle characterized by prodigious predation of soil microbes punctuated by
      periods of dispersal as a non-developing alternative larval stage. During the
      booming periods of population expansion, these animals almost indiscriminately
      consume everything in their environment including any number of compounds from
      other animals, microorganisms, plants, and xenobiotics. Several recent studies
      have identified many genes encoding sensors and enzymes these nematodes may use
      in their xeno-coping strategies. Here, we will discuss these recent advances, as
      well as the efforts by our lab and others to utilize the genomic resources of the
      C. elegans system to elucidate this nematode's molecular defenses against toxins.

PMID- 16902961
TI  - Identification of melanin-concentrating hormone receptor and its impact on drug
      discovery.
AB  - The neuropeptide melanin-concentrating hormone (MCH) was originally isolated from
      the pituitary of salmon, in which it causes skin paling. MCH is also found
      abundantly in mammalian neurons, and has been detected in the lateral
      hypothalamus and zona incerta, brain regions that are at the center of feeding
      behavior. Acute central administration of MCH leads to a rapid and significant
      increase in food intake, while MCH expression changes in states of altered energy
      balance, such as fasting and obesity. Furthermore, MCH knockout mice tend toward
      hypophagia and leanness. In 1999, we and four other groups identified an orphan G
      protein-coupled receptor (GPCR) as a specific receptor for MCH (MCH-1 receptor).
      Although a second MCH receptor (MCH-2 receptor) was isolated in humans, it was
      found to be non-functional or encode a non-functional pseudogene in non-human
      species, including rodents. The discovery of these MCH receptors permitted the
      launch of a broad array of drug screening efforts and three MCH-1 receptor
      antagonists were identified to reduce food intake and body weight. Interestingly,
      some antagonists unexpectedly produced evidence that blockade of these receptors
      has antidepressant and anxiolytic activities. The expressions of the MCH
      receptors, which have been implicated in regulating emotion, stress and
      motivation, make MCH an excellent candidate for integrating the various
      homeostatic stimuli necessary for maintaining the proper conditions of energy
      metabolism and other physiological functions. Finally, the speed at which MCH
      receptor studies have been undertaken exemplifies the impact that this
      deorphanized GPCR will have on setting the stage for more detailed physiological
      studies.

PMID- 16902962
TI  - The stanniocalcin family of proteins.
AB  - Stannniocalcin (STC) is a polypeptide hormone that was originally identified in
      bony fishes as a systemic regulator of mineral metabolism, and is best known for
      its regulatory effects on calcium/phosphate transport by the gills, gut and
      kidneys. The mammalian homolog to fish STC was discovered in 1995 and has
      resulted in progressively growing interest ever since as to its possible role in
      humans. Moreover, new discoveries in the mammalian STC field are resulting in
      significant reappraisals as to its role in fishes. Perhaps the most significant
      of these has been the discovery of a second gene encoding stanniocalcin-related
      protein, or STC-2, first in mammals and subsequently in fish. This review covers
      the comparative endocrinology of the STCs in fishes and mammals from the
      perspectives of structure, function and regulation. It then delves into some of
      the newer aspects of STC-1/STC-2 biology that have been uncovered using both
      classical and transgenic approaches. Of these, one of the most intriguing
      discoveries relates to the receptor-mediated sequestration of STC by target cell
      organelles. The functions of other newly discovered mammalian and fish STC
      variants are also discussed, as is the recent discovery of STC-related homologs
      in invertebrates. Based on our current state of knowledge, it is apparent that
      STC has an ancient lineage and that the STC family of proteins is proving to have
      significant roles in metabolism, reproduction and development.

PMID- 16902963
TI  - Interactions of gonadotropin-releasing hormone (GnRH) and gonadotropin-inhibitory
      hormone (GnIH) in birds and mammals.
AB  - Gonadotropin-releasing hormone (GnRH) regulates secretion of both of the
      gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone. Thus,
      it is a key hormone for vertebrate reproduction. GnRH was considered to be
      unusual among hypothalamic neuropeptides in that it appeared to have no direct
      antagonist, although some neurochemicals and peripheral hormones (opiates, GABA,
      gonadal steroids, inhibin) can modulate gonadotropin release to a degree. Five
      years ago, a vertebrate hypothalamic neuropeptide that inhibited pituitary
      gonadotropin release in a dose-dependent manner was discovered in quail by
      Tsutsui et al. (2000. Biochem Biophys Res Commun 275:661-667). We now know that
      this inhibitory peptide, named gonadotropin-inhibitory hormone, or GnIH, is a
      regulator of gonadotropin release in vitro and in vivo. Its discovery has opened
      the door to an entirely new line of research within the realm of reproductive
      biology. In our collaborative studies, we have begun to elucidate the manner in
      which GnIH interacts with GnRH to time release of gonadotropins and thus time
      reproductive activity in birds and mammals. This paper reviews the distribution
      of GnIH in songbirds relative to GnRHs, and our findings on its modes of action
      in vitro and in vivo, based on laboratory and field studies. These data are
      simultaneously compared with our findings in mammals, highlighting how the use of
      different model species within different vertebrate classes can be a useful
      approach to identify the conserved actions of this novel neuropeptide, along with
      its potential importance to vertebrate reproduction.

PMID- 16902964
TI  - Structures and diverse functions of frog growth hormone-releasing peptide (fGRP)
      and its related peptides (fGRP-RPs): a review.
AB  - A new Arg-Phe-NH(2) (RFamide) peptide has been discovered in the amphibian
      hypothalamus. The cell bodies and terminals containing this peptide were
      localized in the suprachiasmatic nucleus and median eminence, respectively. This
      peptide was further revealed to have a considerable growth hormone (GH)-releasing
      activity in vitro and in vivo and hence designated as frog GH-releasing peptide
      (fGRP). Molecular cloning of cDNA encoding the fGRP precursor polypeptide
      revealed that it encodes fGRP and its putative gene-related peptides (fGRP-RP-1, 
      RP-2, and -RP-3). Subsequently, we identified these putative fGRP-RPs as mature
      peptides and analyzed their hypophysiotropic activities. Only fGRP-RP-2
      stimulated the release of GH and prolactin (PRL) in vitro and in vivo. Thus, in
      addition to fGRP, fGRP-RP-2 acts as a hypothalamic factor on the frog pituitary
      to stimulate the release of GH and PRL.

PMID- 16902965
TI  - The Comparative Toxicogenomics Database (CTD): a resource for comparative
      toxicological studies.
AB  - The etiology of most chronic diseases involves interactions between environmental
      factors and genes that modulate important biological processes (Olden and Wilson,
      2000. Nat Rev Genet 1(2):149-153). We are developing the publicly available
      Comparative Toxicogenomics Database (CTD) to promote understanding about the
      effects of environmental chemicals on human health. CTD identifies interactions
      between chemicals and genes and facilitates cross-species comparative studies of
      these genes. The use of diverse animal models and cross-species comparative
      sequence studies has been critical for understanding basic physiological
      mechanisms and gene and protein functions. Similarly, these approaches will be
      valuable for exploring the molecular mechanisms of action of environmental
      chemicals and the genetic basis of differential susceptibility.

PMID- 16902966
TI  - Unexpected diversity of aryl hydrocarbon receptors in non-mammalian vertebrates:
      insights from comparative genomics.
AB  - Ligand-activated receptors are well-known targets of environmental chemicals that
      disrupt endocrine signaling. Genomic approaches are providing new opportunities
      to understand the comparative biology and molecular evolution of these receptors.
      One example of this is the aryl hydrocarbon receptor (AHR), a basic-helix-loop
      helix (bHLH)-Per-Arnt-Sim (PAS) transcription factor through which planar
      aromatic hydrocarbons cause altered gene expression and toxicity. In contrast to
      humans and other mammals, which possess a single AHR, teleosts such as the
      Atlantic killifish (Fundulus heteroclitus) have at least two AHRs (AHR1 and
      AHR2). Analysis of sequenced genomes has revealed additional, unexpected AHR
      diversity in non-mammalian vertebrates, including the chicken Gallus gallus
      (three predicted AHR genes), bony fishes such as the pufferfish Takifugu
      (formerly Fugu) rubripes (five AHR genes) and zebrafish Danio rerio (three AHR
      genes), and cartilaginous fishes such as the spiny dogfish Squalus acanthias
      (three AHR genes). In contrast, invertebrates appear to possess single AHRs that
      do not bind typical ligands of vertebrate AHRs. We suggest that AHR diversity in
      vertebrates arose through both gene and whole-genome duplications combined with
      lineage-specific gene loss, and that sensitivity to the developmental toxicity of
      planar aromatic hydrocarbons may have had its origin in the evolution of the
      ligand-binding capacity of the AHR in the chordate lineage. Comparative molecular
      and genomic studies are providing new insights into AHR diversity and function in
      non-mammalian species, revealing additional complexity in mechanisms by which
      environmental chemicals interfere with receptor-dependent signaling.

PMID- 16902968
TI  - Proceedings of the XV International Congress of Comparative Endocrinology. May 22
      27, 2005. Boston, Massachusetts, USA.

PMID- 16902967
TI  - Temporal gene induction patterns in sheepshead minnows exposed to 17beta
      estradiol.
AB  - Gene arrays provide a powerful method to examine changes in gene expression in
      fish due to chemical exposures in the environment. In this study, we expanded an
      existing gene array for sheepshead minnows (Cyprinodon variegatus) (SHM) and used
      it to examine temporal changes in gene expression for male SHM exposed to 100 ng
      17beta-estradiol (E(2))/L for five time points between 0 and 48 hr. We found that
      in addition to the induction of genes involved in oocyte development
      (vitellogenin [VTG], zona radiata [ZRP]), other genes involved in metabolism and
      the inflammatory response are also affected. We identified five patterns of
      temporal induction in genes whose expression was modified due to E(2) exposure.
      We validated the gene array data for the expression of VTG 1, VTG 2, ZRP 2 and
      ZRP 3 and found that with low levels of exogenous E(2) (100 ng E(2)/L) exposure,
      ZRP expression precedes VTG expression. However, at higher concentrations of E(2)
      (500 ng E(2)/L), the difference in temporal expression appears to be lost.
      Exposure to high levels of environmental contaminants may affect the normal
      ordered expression of genes required for reproduction. Gene expression profiling
      using arrays promises to be a valuable tool in the field of environmental
      toxicology. As more genes are identified for species used in toxicological
      testing, researchers will be better able to predict adverse effects to chemical
      exposures and to understand the relationships between changes in gene expression
      and changes in phenotype.

PMID- 16902969
TI  - Neurosteroids and the songbird model system.
AB  - The brain is now widely recognized as having the capacity to make steroids,
      neurosteroidogenesis. Although many functions are known for steroids that might
      be made in the brain, the evolution of and natural biological functions for these
      neurosteroids are not fully understood. In songbirds, neurosteroids may function
      in the development of neural circuits controlling song and may also participate
      in the activation of some steroid-dependent behaviors during the non-breeding
      season. In addition to neuroanatomical and behavioral evidence, we have
      physiological, molecular, and biochemical evidence for the expression and
      activity of steroidogenic enzymes in the brains of developing and adult
      songbirds. We review the evidence published so far for songbird
      neurosteroidogenesis and discuss why we believe songbird species are excellent
      models for the study of brain steroid synthesis and action.

PMID- 16902970
TI  - Functions of melanin-concentrating hormone in fish.
AB  - Melanin-concentrating hormone (MCH) was originally discovered in fish, in which
      it causes aggregation or concentration of melanin granules in melanophores, thus
      regulating body color. MCH is a cyclic neuropeptide synthesized as a
      preprohormone in the hypothalamus of all vertebrates. Mammalian MCH plays an
      important role as a neurotransmitter or neuromodulator in regulating food intake
      and energy homeostasis. MCH signaling system may involve in regulating food
      intake also in fish. This neuropeptide binds to G-protein-coupled seven
      transmembrane receptor[s] to mediate its functions. This article reviews MCH and
      MCH receptor signaling systems in body color change and food intake in fish.

PMID- 16902971
TI  - Major contributions of comparative endocrinology to the development and
      exploitation of the incretin concept.
AB  - An incretin is a factor released by the gut in response to nutrients that
      facilitates uptake of glucose by peripheral tissues. The incretin concept
      predates the discovery of insulin but it is now clear that incretins act by
      stimulating secretion of this hormone. As glucagon has insulin-releasing
      activity, it was speculated that intestinal glucagon-like immunoreactivity
      (enteroglucagon) was involved in the incretin effect but it was an achievement in
      the field of comparative endocrinology that led to the demonstration that the
      preproglucagon gene encodes the most potent incretin in the human.
      Characterization of cloned cDNAs encoding two preproglucagons from the Brockmann
      body of the anglerfish Lophius americanus demonstrated that the glucagon sequence
      is flanked by a 34 amino-acid-residue sequence with appreciable structural
      similarity to glucagon that was termed glucagon-like peptide (GLP). A 36 amino
      acid-residue ortholog of anglerfish GLP was subsequently identified in human
      preproglucagon but this peptide had only weak insulin-releasing activity.
      However, alignment of GLP sequences from human and teleost fish showed that the
      human ortholog is extended from its N-terminus by a hexapeptide. Removal of this
      extension by an endogenous protease generates GLP-1-(7-36)amide, the potent and
      effective form of the incretin. More recently, comparative endocrinology has
      contributed to the exploitation of incretins as antidiabetic drugs. Exendin-4, a
      GLP-1 receptor agonist first isolated from the venom of the Gila monster
      Heloderma suspectum, is a clinically valuable, long-acting incretin and the skins
      of several species of frogs synthesize potent insulin-releasing peptides with
      therapeutic potential.

PMID- 16902972
TI  - Prostate cancer metastasis: role of the host microenvironment in promoting
      epithelial to mesenchymal transition and increased bone and adrenal gland
      metastasis.
AB  - BACKGROUND: The ARCaP cell line was established from the ascites fluid of a
      patient with metastatic prostate cancer. This study characterized the host
      microenvironmental role in cancer progression, epithelial to mesenchymal
      transition (EMT), and bone and adrenal metastasis in parental ARCaP and its
      derived cell subclones. METHODS: Cytogenetic profiles, growth, migration,
      invasion, cellular interaction, drug sensitivities, and gene expression of ARCaP
      cell subclones were compared. In vivo gene expression, behavior, and metastasis
      of ARCaP subclones were analyzed by serial intracardiac injections into SCID
      mice. RESULTS: ARCaP(E) cells, with cobblestone morphology, underwent EMT through
      cellular interaction with host bone and adrenal gland. Lineage-derived ARCaP(M)
      cells, with spindle-shape fibroblastic morphology, exhibited decreased cell
      adhesion and increased metastasis to bone and adrenal gland. Cytogenetic analyses
      of parental and ARCaP subclones confirmed their clonality. CONCLUSIONS: ARCaP
      uniquely models the molecular basis of prostate cancer bone and adrenal
      metastases and epithelial to mesenchymal transition.

PMID- 16902973
TI  - Blood velocity assessment using 3D bright-blood time-resolved magnetic resonance
      angiography.
AB  - Blood velocity is a functional parameter that is not easily assessed
      noninvasively, especially in small animals. A new noninvasive method that uses
      magnetic resonance angiography (MRA) to measure blood flows is proposed. This
      method is based on the time-of-flight (TOF) phenomenon. By initially suppressing
      the signal from the stationary spins in the area of interest, it is possible to
      sequentially visualize only the signal from the moving spins entering a given
      volume. With this method, 3D cine images of the blood flow can be generated by
      positive contrast, with unparalleled spatial (<200 microm) and temporal
      resolutions (<10 ms/image). As a result, it is possible to measure flow in
      sinuous paths. The present method was applied in vivo to measure the blood
      velocity in mouse carotid arteries. Because of its robustness and simplicity of
      implementation, this method has numerous potential applications for fundamental
      studies in small animal models.

PMID- 16902974
TI  - Vascular wall elasticity measurement by magnetic resonance imaging.
AB  - The goal of this current study was to determine whether an MRI-based elastography
      (MRE) method can visualize and assess propagating mechanical waves within fluid
      filled vessels and to investigate the feasibility of measuring the elastic
      properties of vessel walls and quantitatively assessing stenotic lesions by using
      MRE. The ability to measure the Young's modulus-wall thickness product was tested
      using a thin-walled latex vessel model. Also tested in vessel models was the
      ability to quantitate the degree of stenosis by measuring transmitted and
      reflected mechanical waves. This method was then applied to ex vivo porcine
      models and in vivo human arteries to further test its feasibility. The results
      provide preliminary evidence that MRE can be used to quantitatively assess the
      stiffness of blood vessels, and provide a non-morphologic method to measure
      stenosis. With further development, it is possible that the method can be
      implemented in vivo.

PMID- 16902975
TI  - Modified Alderman-Grant resonator with high-power stability for proton electron
      double resonance imaging.
AB  - Proton-electron double resonance imaging (PEDRI) requires a dual EPR/NMR
      resonator. In order to saturate electron spins, long high-power RF EPR pulses are
      needed. Dissipated power causes resonator and sample heating, resulting in
      instability of the resonator frequency and coupling, which in turn causes a
      reduction in sensitivity. To overcome this problem, we designed, built, and
      tested a modified Alderman-Grant (MAG) resonator for in vivo and in vitro
      applications. We improved the temperature stability by using fused quartz in
      critical structural components of the resonator and employing a design that
      minimized moving parts. All of the components of the resonator and matching
      circuit, including coupling capacitors, were rigidly positioned on the surface of
      the quartz tube. Electrical coupling circuitry between the feeding cable and
      resonator was employed to provide independent coupling and tuning adjustments,
      which improved the ease and speed of operation. The equivalent schematic of the
      matching circuit is presented along with calculations of critical parameters. The
      resonator exhibits no frequency shift with 20 W of continuous power irradiation,
      and can handle intermittent power of 60 W for up to 3 min without detuning,
      enabling stable and reliable data acquisition for PEDRI of biological samples.

PMID- 16902976
TI  - SENSE optimization of a transceive surface coil array for MRI at 4 T.
AB  - Parallel imaging (PI) techniques employ the use of multiple radiofrequency (RF)
      channels to transmit and/or receive the NMR signal. In the current study we use a
      finite difference time domain (FDTD) method to simulate the electromagnetic
      fields of a RF coil array operating in transmit-receive (transceive) mode and
      receive-only mode. Optimization of these configurations for PI is studied as
      well. Our results suggest that a coil array can effectively be used for
      transceive or receive-only PI techniques. For a head coil configuration, the
      sensitivity encoding (SENSE) optimized coil array gap size and PI acceleration
      factor for MRI are shown to be a function of the physiological-to-intrinsic-noise
      ratio (PhINR) with a much stronger dependence on acceleration factor than gap
      size. The results provide a means to optimize any PI sequence by varying the
      acceleration factor based on the measured PhINR. In addition, an example design
      for an eight-element transceive coil array for heads at 4 T is given.

PMID- 16902977
TI  - MRI to detect atherosclerosis with gadolinium-containing immunomicelles targeting
      the macrophage scavenger receptor.
AB  - The ability to specifically image macrophages may enable improved detection and
      characterization of atherosclerosis. In this study we evaluated the in vitro
      uptake of gadolinium (Gd)-containing immunomicelles (micelles linked to
      macrophage-specific antibody), micelles, and standard contrast agents by murine
      macrophages, and sought to determine whether immunomicelles and micelles improve
      ex vivo imaging of apolipoprotein E knockout (ApoE KO) murine atherosclerosis.
      Murine RAW 264.7 macrophages were incubated with Gd-DTPA, micelles, and
      immunomicelles. Cell pellets were prepared and imaged using a 1.5 T MR system
      with an inversion recovery spin-echo sequence to determine the in vitro T1
      values. Ex vivo analysis of mouse aortas was performed using a 9.4T MR system
      with a high-spatial-resolution sequence (78x39x78 microm3). The T1 value was
      significantly decreased in cells treated with micelles compared to Gd-DTPA
      (P<0.0001), and in cells incubated at 4 degrees C with immunomicelles compared to
      micelles (P<0.05). Ex vivo MRI signal intensity (SI) was significantly increased
      by 81% and 20% in aortas incubated with immunomicelles and micelles,
      respectively. Confocal microscopy demonstrated in vitro and ex vivo uptake of
      fluorescent immunomicelles by macrophages. Immunomicelles and micelles improve in
      vitro and ex vivo MR detection of macrophages, and may prove useful in the
      detection of macrophage-rich plaques.

PMID- 16902978
TI  - Temporal correlation-based dynamic contrast-enhanced MR imaging improves
      assessment of complex pulmonary circulation in congenital heart disease.
AB  - A temporal correlation (TC) mapping method is proposed to help bolus chasing
      during dynamic contrast-enhanced (DCE) MRI of complex pulmonary circulation (CPC)
      in patients with congenital heart disease. DCE-MRI was performed on five healthy
      male subjects (23-24 years old) and 25 patients (nine males and 16 females, 0.25
      44 years old), and TC maps were generated by performing pixel-based computation
      of cross-correlations to the pulmonary artery with a series of time shifts in all
      subjects. Qualitative and quantitative evaluations were performed in comparison
      with original DCE images. TC maps exhibited a better signal-to-noise ratio (SNR)
      by factors of 4.3 and 1.3 in the lung parenchyma, pulmonary veins, and superior
      artery/vein; a better intraparenchymal contrast-to-noise ratio (CNR) by factors
      of 1.5-5.4; and a significantly higher conspicuity in all regions except the
      pulmonary arteries when graded with a five-point score. TC maps evaluated by two
      experienced clinicians significantly added relevant information (P<0.001), and in
      some cases affected the final diagnosis. We conclude that TC maps facilitate
      bolus chasing for DCE-MRI by reducing recirculation effects and interframe
      fluctuations, and hence complements morphological imaging of CPC in patients with
      complex congenital heart disease.

PMID- 16902979
TI  - Three-dimensional magnetic resonance microscopy of pulmonary solitary tumors in
      transgenic mice.
AB  - We attempted to accurately detect pulmonary solitary tumors and other complicated
      pulmonary disorders in aging inbred transgenic mice by cardiac- and respiratory
      gated MR microscopy at 4.7 Tesla. A comparison of in vivo MR images with
      histological results demonstrated that submillimeter lung tumors and most of the
      nontumor lesions could be detected by screening with two-dimensional (2D)
      gradient echo (GRE) imaging. Subsequently performed 2D spin-echo (SE) imaging
      provided higher image contrast, which distinguished the tumors from the
      surrounding complications. On the 3D GRE images and the generated maximum
      intensity projection (MIP) and volume-rendered (VR) images, proper spatial
      localization of solitary tumors relative to the orientation of the pulmonary
      vessels was exhibited, and the tumor volume could also be measured. This
      promising method is noninvasive and has the potential to eventually replace
      invasive histopathology because it obviates the need to kill groups of animals at
      multiple time points.

PMID- 16902980
TI  - Efficient visualization of vascular territories in the human brain by cycled
      arterial spin labeling MRI.
AB  - Intracranial vascular territories are usually visualized with the use of
      angiographic techniques. However, because it is difficult to visualize the distal
      vascular bed with any angiographic technique, it is also difficult to infer the
      parenchymal borders of vascular territories. Arterial spin labeling (ASL) MRI
      provides information on cerebral perfusion, and a regional ASL (regASL) approach
      offers the potential to visualize perfusion of the anterior and posterior
      circulation separately. Current techniques perform the labeling in each feeding
      artery as a separate experiment, which is very time-consuming. In this work a
      very time-efficient regASL technique is presented that acquires all vascular
      territories within the same experiment. Images with different combinations of
      labeled arteries are combined to delineate the vascular territory of interest.
      Five subjects were examined with a clinical 1.5T MR scanner. A sharp delineation
      of the middle cerebral artery (MCA) and posterior cerebral artery (PCA)
      territories with whole-brain coverage was achieved in all subjects. The resulting
      signal-to-noise ratios (SNRs) for conventional regASL and the proposed cycled
      regASL were 9.3+/-2.4 and 15.3+/-5.1, respectively. An optimized setup was
      achieved by combining the regional labeling scheme with an efficient readout
      technique, which yielded a total measurement time of 2 min for three vascular
      territories.

PMID- 16902981
TI  - Contrast enhanced MRI-guided photodynamic therapy for site-specific cancer
      treatment.
AB  - Photodynamic therapy (PDT) is a minimally invasive and effective approach for
      cancer treatment. It is potentially useful for treating tumors that are not
      accessible to surgery, radiation, or destructive ablations, and are resistant to
      chemotherapy. Efficacious treatment of interstitial tumors with PDT requires
      efficient delivery of photosensitizers and accurate location of tumor tissues for
      effective light irradiations. In this study we performed contrast-enhanced (CE)
      MRI-guided PDT with a bifunctional polymer conjugate containing both a magnetic
      resonance imaging (MRI) contrast agent and a photosensitizer, poly(L-glutamic
      acid) (PGA)-(Gd-DO3A)-mesochlorin e(6) (Mce(6)). The efficacy of the bifunctional
      conjugate in cancer CE-MRI and cancer treatment was evaluated in athymic nude
      mice bearing MDA-MB-231 human breast carcinoma xenografts, with PGA-(Gd-DO3A)
      used as a control. The polymer conjugates preferentially accumulated in the solid
      tumor due to the hyperpermeability of the tumor vasculature, resulting in
      significant tumor enhancement for accurate tumor detection and localization by
      MRI. Significant therapeutic response was observed for PDT with the bifunctional
      conjugate as compared to the control. CE-MRI-guided PDT with the bifunctional
      conjugate is effective for tumor detection and minimally invasive cancer
      treatment.

PMID- 16902982
TI  - Optimal acquisition schemes for in vivo quantitative magnetization transfer MRI.
AB  - This paper uses the theory of Cramer-Rao lower bounds (CRLB) to obtain optimal
      acquisition schemes for in vivo quantitative magnetization transfer (MT) imaging,
      although the method is generally applicable to any multiparametric MRI technique.
      Quantitative MT fits a two-pool model to data collected at different sampling
      points or settings of amplitude and offset frequency in the MT saturation pulses.
      Here we use simple objective functions based on the CRLB to optimize sampling
      strategies for multiple parameters simultaneously, and use simulated annealing to
      minimize these objective functions with respect to the sampling configuration.
      Experiments compare optimal schemes derived for quantitative MT in the human
      white matter (WM) at 1.5T with previously published schemes using both synthetic
      and human-brain data. Results show large reductions in error of the fitted
      parameters with the new schemes, which greatly increases the clinical potential
      of in vivo quantitative MT. Since the sampling-scheme optimization requires
      specific settings of the MT parameters, we also show that the optimum schemes are
      robust to these settings within the range of MT parameters observed in the brain.

PMID- 16902983
TI  - The influence of family history on breast cancer risk in women with biopsy
      confirmed benign breast disease: results from the Nurses' Health Study.
AB  - BACKGROUND: An association between histologic category of benign breast disease
      (BBD) and breast cancer risk has been well documented. However, the influence of
      a positive family history (FH) on breast cancer risk among women with biopsy
      confirmed BBD is less certain. METHODS: The authors conducted a nested case
      control study of BBD and breast cancer risk among 2005 women who were enrolled in
      the Nurses' Health Study. Cases were women with breast cancer who had a previous
      benign breast biopsy (n = 395 women). Controls were women who also had previous
      biopsy-confirmed BBD but were free from breast cancer at the time the
      corresponding case was diagnosed (n = 1610 women). BBD slides were reviewed and
      categorized as either nonproliferative lesions, proliferative lesions without
      atypia, or atypical hyperplasia (AH). RESULTS: Compared with women who had
      nonproliferative lesions and no FH, women who had proliferative lesions without
      atypia and a positive FH had a higher breast cancer risk (odds ratio [OR], 2.45;
      95% confidence interval [95% CI], 1.61-3.70) than women with no FH (OR, 1.51; 95%
      CI, 1.12-2.06; P = .07). Among women who had AH, the OR for the development of
      breast cancer was 4.38 (95% CI, 2.93-6.55) for those with no FH and 5.37 (95% CI,
      3.01-9.58) for those with a positive FH (P = .57). There was no significant
      interaction between the type of BBD and FH (P = .74). CONCLUSIONS: A positive FH
      of breast cancer slightly increased the breast cancer risk among women who had
      proliferative lesions without atypia. The increase in risk of breast cancer
      associated with FH was not significant among women who had AH.

PMID- 16902984
TI  - Hodgkin transformation of chronic lymphocytic leukemia: the M. D. Anderson Cancer
      Center experience.
AB  - BACKGROUND: Hodgkin transformation is a rare complication of chronic lymphocytic
      leukemia/small lymphocytic lymphoma (CLL/SLL). In this study, the authors
      assessed the incidence, presenting characteristics, and outcomes of patients with
      CLL/SLL who developed Hodgkin lymphoma (HL). METHODS: An electronic database
      search of patients with CLL/SLL who presented at The University of Texas M. D.
      Anderson Cancer Center Department of Leukemia between 1975 and 2005 was
      performed. RESULTS: Among 4121 patients with CLL/SLL, 18 patients (0.4%)
      developed HL. Presenting features included B-symptoms (67%), lymph node
      enlargement (79%), splenomegaly (43%), hepatomegaly (29%), hypercalcemia (6%),
      infection (6%), and mental status changes (6%). The median age was 72 years
      (range, 49-81 years), and there was a male preponderance (78%). The median time
      from CLL to HL diagnosis was 4.6 years (range, 0-12.9 years). Fourteen patients
      (78%) had been previously treated for CLL/SLL. Ten patients (56%) had received >1
      prior therapy. The median beta2-microglobulin level was 4.5 mg/L, and the median
      lactate dehydrogenase level was 610 IU/L. Epstein-Barr virus (EBV) was positive
      by in situ hybridization for EBV-encoded RNA in 3 of 4 tested patients. Fourteen
      patients (78%) received chemotherapy. The overall response rate was 44% (complete
      response rate, 19%). The median overall survival duration was 0.8 years (range,
      0.03 years-6.7+ years). The median failure-free survival (FFS) duration was 0.4
      years. CONCLUSIONS: The rates of response, survival, and FFS in patients with
      Hodgkin transformation of CLL/SLL were inferior to those reported in patients
      with de novo HL and were similar to those in patients with Richter syndrome.

PMID- 16902985
TI  - Toxicity and outcome of a phase II trial of taxane-based neoadjuvant chemotherapy
      and 3-dimensional, conformal, accelerated radiotherapy in locally advanced
      nonsmall cell lung cancer.
AB  - BACKGROUND: The objective of this study was to evaluate prospectively the acute
      and late adverse effects of taxane/carboplatin neoadjuvant chemotherapy and 3
      dimensional, conformal radiotherapy in patients with locally advanced nonsmall
      cell lung cancer (NSCLC). METHODS: Forty-two patients were entered into a
      nonrandomized Phase II study of continuous, hyperfractionated, accelerated
      radiotherapy (CHART) week-end less (CHARTWEL) to a dose of 60 grays (Gy). Three
      cycles of chemotherapy were given over 9 weeks before radiotherapy. Dose
      escalation with paclitaxel was from 150 mg/m2 to 225 mg/m2. Systemic toxicity to
      chemotherapy was monitored throughout. Radiation-induced, early, adverse effects
      were assessed during the first 9 weeks from the start of radiotherapy, and late
      effects were assessed from 3 months onward. Overall survival, disease-free
      survival, and locoregional tumor control also were monitored. RESULTS: Twenty
      percent of patients failed to receive chemotherapy as planned, primarily because
      of neutropenia. The incidence of Dische Dictionary Grade >or=2 and Grade >or=3
      dysphagia was 57.5% and 10%, respectively, with an average duration of 1.2 weeks
      and 1.5 days, respectively. By 9 weeks, <3% of patients were symptomatic; and,
      eventually, all acute reactions were healed, and there has been no evidence of
      consequential damage. At 6 months, the actuarial incidence of moderate-to-severe
      pneumonitis was 10%. During this time, all patients were free of severe pulmonary
      complications. Actuarial estimates of Grade >or=2 late lung dysfunction were 3%
      at 1 year, 10% at 2 years, and remained at this level thereafter. The actuarial 3
      year locoregional control and overall survival rates were 54% and 45%,
      respectively. CONCLUSIONS: Neoadjuvant chemotherapy followed by 3-dimensional,
      conformal CHARTWEL 60-Gy radiotherapy in patients with advanced NSCLC was
      feasible and was tolerated well. Historic comparisons indicated that locoregional
      tumor control is not compromised by the use of conformal techniques.

PMID- 16902986
TI  - Noninvasive magnetic resonance thermography of soft tissue sarcomas during
      regional hyperthermia: correlation with response and direct thermometry.
AB  - BACKGROUND: The objective of this study was to evaluate noninvasive magnetic
      resonance (MR) thermography for the monitoring of regional hyperthermia (RHT) in
      patients with soft tissue sarcomas of the lower extremities and pelvis. METHODS:
      Noninvasive MR monitoring during RHT was performed in 9 patients who had high
      risk soft tissue sarcomas of the lower extremities or pelvis during neoadjuvant
      chemotherapy plus RHT in the scope of the European Organization for Research and
      Treatment of Cancer 62961/European Society for Hyperthermic Oncology RHT-95
      study. Anatomic and temperature-sensitive data sets were acquired every 10
      minutes before and during RHT (using gradient-echo-sequences with variable echo
      times). MR temperature distributions were derived from the phase differences by
      using the proton-resonance frequency shift method. A phase convolution setting
      phase shifts to zero in the fat tissue was performed as a drift correction. The
      mean MR temperatures in the tumor and muscles and the index temperatures (e.g.,
      T90, which covers 90% of the target volume) and thermal doses were determined and
      compared with pathohistologic responses and direct temperature measurements if
      available. RESULTS: Thirty of 72 MR-thermography data sets (>40% of heat
      sessions) were evaluable. A significant correlation was observed between
      pathohistologic response (defined as a necrosis rate >or=90%) and standardized
      thermal parameters, such as thermal dose cumulative equivalent minutes at 43
      degrees C to 90% of the target volume (T90) (P = .050), mean T90 (P = .048), or
      T50 (P = .050). The correlation of 13 conventional temperature measurements
      performed in selected patients and sessions invasively in the tumor or
      noninvasively in rectum and bladder revealed an excellent correlation with MR
      temperatures (R2 = .96). CONCLUSIONS: Noninvasive MR thermography of soft tissue
      sarcoma was feasible and suitable for validating the quality of heating during
      RHT.

PMID- 16902988
TI  - Interleukin-13 receptor alpha2 chain: a potential biomarker and molecular target
      for ovarian cancer therapy.
AB  - BACKGROUND: Epithelial ovarian cancer demonstrates high mortality due to
      diagnosis at an advanced stage. In the search for a biomarker for early diagnosis
      and a target for therapy, the issue of whether interleukin-13 receptor (IL-13R),
      shown to be expressed on a variety of human cancers, is expressed in ovarian
      tumor samples was explored. In addition, whether this receptor serves as a
      biomarker and can be targeted by IL-13 cytotoxin was examined. METHODS: IL-13R
      expression in 15 normal and 68 ovarian tumor tissue samples was determined by
      immunohistochemistry. Correlation between clinicopathologic features and IL-13R
      expression was analyzed. The efficacy of IL-13R-directed cytotoxin was determined
      in mice with subcutaneous, orthotopic, and peritoneal metastatic ovarian cancer.
      RESULTS: Immunohistochemical analyses revealed that 83% of ovarian cancer
      specimens express IL-13Ralpha2, a high-affinity IL-13R subunit chain, whereas
      normal ovary samples expressed none or very low levels. The majority of clear
      cell ovarian carcinomas with the worst prognosis showed strong staining for IL
      13Ralpha2. IL-13 cytotoxin was highly cytotoxic to the IGROV-1 ovarian cancer
      cell line in vitro, and it mediated significant antitumor activity against a
      xenografted tumor model. The antitumor effects were confirmed by treating
      orthotopically implanted or peritoneal metastatic ovarian tumors, which showed
      significant extension of survival in immunodeficient mice. IL-13 cytotoxin also
      prevented cachexia in treated mice. The soluble form of IL-13Ralpha2 was detected
      in the serum of mice with peritoneal metastasis, and the level decreased to
      baseline in the treated group. CONCLUSIONS: IL-13Ralpha2 is a promising target
      for ovarian cancer therapy, and the soluble form of IL-13R may be a possible
      surrogate marker for disease monitoring.

PMID- 16902987
TI  - Phase I study to determine the safety and pharmacokinetics of oral administration
      of TAS-102 in patients with solid tumors.
AB  - BACKGROUND: The purpose of the current study was to determine the maximum
      tolerated dose, dose-limiting toxicities, pharmacokinetic profile, and
      recommended Phase II dose of oral administration of TAS-102, a novel nucleoside
      formed by the combination of alpha,alpha,alpha-trifluorothymidine (FTD) and a
      thymidine phosphorylase inhibitor (TPI: 5-chloro-6-(2-iminopyrrolidin-1-yl)methyl
      2,4(1H,3H)-pyrimidinedione). METHODS: Eligible patients had advanced solid
      tumors, adequate organ function, and had not received anticancer therapy in the
      preceding 4 weeks. TAS-102 was administered orally once daily for 14 days,
      followed by a 1-week rest, repeated every 3 weeks. The initial dose of TAS-102
      administered was 100 mg/m2/day. The first 2 patients treated at that dose
      experienced substantial toxicity and, therefore, lower dose levels of TAS-102
      were subsequently explored. RESULTS: Fourteen patients were enrolled; all
      patients were evaluable for toxicity assessment and 12 were evaluable for
      response. The initial dose explored was 100 mg/m2/day, based on a preclinical
      monkey model. However, the first 2 patients experienced bone marrow suppression
      of Grade 3 or 4 in course 1. The protocol was amended to study the next cohort of
      patients at 50 mg/m2/day. At this dose level no Grade 3 or 4 toxicities were
      observed in course 1. In the subsequent dose level (60 mg/m2/day), 3 of 6
      patients experienced Grade 3 or 4 granulocytopenia as dose-limiting toxicity.
      Three additional patients for a total of 6 were enrolled at 50 mg/m2/day without
      occurrence of dose-limiting toxicity. Thus, 50 mg/m2/day was declared the maximum
      tolerated dose for this schedule. CONCLUSIONS: The authors' study showed that 50
      mg/m2/day was a tolerable dose of the novel antimetabolite FTD in combination
      with an inhibitor of its inactivating enzyme TP, and this is the recommended
      Phase II dose. Evaluation of this daily dose in malignancies for which
      fluoropyrimidines have failed is needed.

PMID- 16902989
TI  - Spatial restriction of spontaneous activity towards the rostral primary
      initiating zone during development of the embryonic mouse hindbrain.
AB  - In the developing embryonic mouse hindbrain, we have previously shown that
      synchronized spontaneous activity is driven by midline serotonergic neurons at
      E11.5. This is mediated, at least in part, by the 5-HT2A receptor, which is
      expressed laterally in the hindbrain. Activity at E11.5 is widespread within the
      hindbrain tissue, propagating from the midline to more lateral regions. Using
      rapid acquisition of [Ca2+]i events along the midline, we now show that the
      rostral midline, primarily in the region of former rhombomere r2, is the primary
      initiating zone for this activity. We propose that at E11.5, the combined events
      along the rostral-caudal axis in combination with events propagating along the
      medial-lateral axis could assign positional information to developing neurons
      within the hindbrain. With further development, to E13.5, both the lateral and
      caudal dimensions of spontaneous activity retract to the rostral midline,
      occupying an area only 14% of that exhibited at E11.5. We also show that
      increased levels of [K+]o (to 8 mM) at E13.5 are able to increase the spread of
      spontaneous activity laterally and rostro-caudally. This suggests that
      spontaneous activity in the hindbrain depends in a dynamic way on the dominant
      initiating zone of the rostral midline, and that this relationship changes over
      development.

PMID- 16902990
TI  - Intersegmental transfer of sensory signals in the stick insect leg muscle control
      system.
AB  - Intersegmental coordination during locomotion in legged animals arises from
      mechanical couplings and the exchange of neuronal information between legs. Here,
      the information flow from a single leg sense organ of the stick insect Cuniculina
      impigra onto motoneurons and interneurons of other legs was investigated. The
      femoral chordotonal organ (fCO) of the right middle leg, which measures posture
      and movement of the femur-tibia joint, was stimulated, and the responses of the
      tibial motoneuron pools of the other legs were recorded. In resting animals, fCO
      signals did not affect motoneuronal activity in neighboring legs. When the
      locomotor system was activated and antagonistic motoneurons were bursting in
      alternation, fCO stimuli facilitated transitions from flexor to extensor activity
      and vice versa in the contralateral leg. Following pharmacological treatment with
      picrotoxin, a blocker of GABA-ergic inhibition, the tibial motoneurons of all
      legs showed specific responses to signals from the middle leg fCO. For the
      contralateral middle leg we show that fCO signals encoding velocity and position
      of the tibia were processed by those identified local premotor nonspiking
      interneurons known to contribute to posture and movement control during standing
      and voluntary leg movements. Interneurons received both excitatory and inhibitory
      inputs, so that the response of some interneurons supported the motoneuronal
      output, while others opposed it. Our results demonstrate that sensory information
      from the fCO specifically affects the motoneuronal activity of other legs and
      that the layer of premotor nonspiking interneurons is a site of interaction
      between local proprioceptive sensory signals and proprioceptive signals from
      other legs.

PMID- 16902991
TI  - Primary role of the serotonergic midline system in synchronized spontaneous
      activity during development of the embryonic mouse hindbrain.
AB  - In the developing embryonic mouse hindbrain, we have shown that previously
      widespread synchronized spontaneous activity at E11.5 retracts to the initiating
      zone of the rostral hindbrain by E13.5, and ceases completely by E14.5. We now
      confirm that at E11.5 and E13.5, the primary driver of spontaneous activity is
      serotonergic input, while other transmitters (GABA, glutamate, NE, and ATP) have
      only modulatory roles. Using immunocytochemistry, we also show that at E13.5, 5
      HT-positive neurons in the midline extend over a larger rostro-caudal distance
      than at E11.5, and that in the presumptive initiating zone, cell bodies occupy a
      band that extends 200 microm laterally on each side of the midline, with
      extensive axonal processes. The 5-HT2A receptor retains expression in lateral
      tissue over this developmental time. We find that in addition to being sensitive
      to 5-HT receptor antagonists, spontaneous activity is also abolished by blockers
      of gap junctions, and is increased in frequency and lateral spread by application
      of ammonium, presumably via increased intracellular pH augmenting gap junction
      conductance. Thus, 5-HT neurons of the midline remain the primary drivers of
      spontaneous activity at several stages of development in the hindbrain, relying
      in part on gap junctional communication during initiation of activity.

PMID- 16902992
TI  - A mouse strain difference in tumorigenesis induced by biodegradable polymers.
AB  - The use of poly-L-lactic acid (PLLA) surgical implants for repair of bone
      fractures has gained popularity in the past decade. The aim of this study was to
      evaluate the in vivo effect of PLLA plates on subcutaneous tissue in two mouse
      strains, BALB/cJ and SJL/J, which have higher and lower tumorigenicity,
      respectively. Gap-junctional intercellular communication and protein expression
      of connexin 43 were significantly suppressed, whereas secretion of transforming
      growth factor-beta1 and expression of extracellular matrix, insulin-like growth
      factor binding protein 3, and cysteine-rich intestinal protein 2 were
      significantly increased in PLLA-implanted BALB/cJ mice when compared with BALB/cJ
      controls. Finally, tumors were formed after implantation of cultured cells from
      the more-tumorigenic BALB/cJ, but not SJL/J, mice into nude mice.

PMID- 16902993
TI  - An innovative online VFA monitoring system for the anerobic process, based on
      headspace gas chromatography.
AB  - A new method for online measurement of volatile fatty acids (VFA) in anerobic
      digesters has been developed based on headspace gas chromatography (HSGC). The
      method applies ex situ VFA stripping with variable headspace volume and gas
      analysis by gas chromatography-flame ionization detection (GC-FID). In each
      extraction, digester sample was acidified with H(3)PO(4) and NaHSO(4), then
      heated to strip the VFA into the gas phase. The gas was sampled in a low friction
      glass syringe before injected into the GC for measurement. The system has been
      tested for online monitoring of a lab-scale CSTR reactor treating manure for more
      than 6 months and has shown good agreement with off-line analysis. The system is
      capable of measuring individual VFA components. This is of advantage since
      specific VFA components such as propionic and butyric acid can give extra
      information about the process status. Another important advantage of this sensor
      is that there is no filtration, which makes possible application in high solids
      environments. The system can thus be easily applied in a full-scale biogas
      reactor by connecting the system to the liquid circulation loop to obtain fresh
      sample from the reactor. Local calibration is needed but automatic calibration is
      also possible using standard addition method. Sampling duration is 25-40 min,
      depending on the washing duration, and sensor response is 10 min. This is
      appropriate for full-scale reactors, since dynamics within most biogas reactors
      are of the order of several hours.

PMID- 16902994
TI  - Polyyne synthesis using carbene/carbenoid rearrangements.
AB  - Rearrangement of a carbene/carbenoid intermediate to form an acetylene moiety,
      known as the Fritsch-Buttenberg-Wiechell (FBW) rearrangement, was developed for
      the formation of polyynes and polyyne frameworks within highly conjugated organic
      materials. Necessary precursors can be prepared through formation of an alkynyl
      ketone, followed by dibromoolefination under Corey-Fuchs conditions. The
      carbenoid rearrangement is brought about by treatment of the dibromoolefin with
      BuLi under mild conditions. The success of these FBW reactions is quite solvent
      dependent, and nonpolar hydrocarbon solvents (e.g., hexanes, toluene, benzene)
      work quite well, while use of ethereal solvents such as diethyl ether and
      tetrahydrofuran (THF) does not provide the desired polyyne product. This protocol
      was successfully applied to the formation of silyl, alkyl, alkenyl, and aryl
      polyynes, including di-, tri-, and tetrayne products, as well as the construction
      of two-dimensional carbon-rich molecules. A one-pot variant of this procedure is
      being developed and is particularly applicable toward the synthesis of polyyne
      natural products. Formation of a series of triisopropylsilyl end-capped polyynes,
      from the triyne to decayne, was achieved. Third-order nonlinear optical
      properties of these polyynes were evaluated. This study shows that the molecular
      second hyperpolarizabilities for the polyynes as a function of length increase at
      a rate that is higher than all other nonaromatic organic oligomers.

PMID- 16902996
TI  - Estrogen treatment of spinal cord injury attenuates calpain activation and
      apoptosis.
AB  - Spinal cord injury (SCI) is a devastating neurologic injury, and currently, the
      only recommended pharmacotherapy is high-dose methylprednisolone, which has
      limited efficacy. Estrogen is a multi-active steroid with anti-oxidant and anti
      apoptotic effects. Estrogen may modulate intracellular Ca2+ and prevent
      inflammation. For this study, male rats were divided into three groups. Sham
      group animals received a laminectomy at T12. Injured rats received both
      laminectomy and 40 gram centimeter force SCI. Estrogen-group rats received 4
      mg/kg 17beta-estradiol (estrogen) at 15 min and 24 hr post-injury, and vehicle
      group rats received equal volumes of dimethyl sulfoxide. Animals were sacrificed
      at 48 hr post-injury, and 1-cm segments of the lesion, rostral penumbra, and
      caudal penumbra were excised. The degradation of 68 kD neurofilament protein
      (NFP) and estrogen receptors (ER) was examined by Western blot analysis. Protein
      levels of calpain and the activities of calpain and caspase-3 were also examined.
      Levels of cytochrome c were determined in both cytosolic and mitochondrial
      fractions. Cell death with DNA fragmentation was examined using the TUNEL assay.
      At the lesion, samples from both vehicle and estrogen treated animals showed
      increased levels of 68 kD NFP degradation, calpain content, calpain activity,
      cytochrome c release, and degradation of ERalpha and ERbeta, as compared to sham.
      In the caudal penumbra, estrogen treatment significantly attenuated 68 kD NFP
      degradation, calpain content, calpain activity, levels of cytosolic cytochrome c,
      and ERbeta degradation. At the lesion, vehicle-treated animals displayed more
      TUNEL+ cells, and estrogen treatment significantly attenuated this cell death
      marker. We conclude that estrogen may inhibit cell death in SCI through calpain
      inhibition.

PMID- 16902995
TI  - Intrathecal injection of epidermal growth factor and fibroblast growth factor 2
      promotes proliferation of neural precursor cells in the spinal cords of mice with
      mutant human SOD1 gene.
AB  - We investigated three steps of neural precursor cell activation--proliferation,
      migration, and differentiation--in amyotrophic lateral sclerosis spinal cord
      treated with intrathecal infusion of epidermal growth factor (EGF) and fibroblast
      growth factor 2 (FGF2) into the lumbar spinal cord region of normal and
      symptomatic transgenic (Tg) mice with a mutant human Cu/Zn superoxide dismutase
      (SOD1) gene. We observed that 5-bromodeoxyuridine (BrdU) + nestin double-labeled
      neural precursor cells increased in the spinal cords of Tg mice compared with non
      Tg mice, with a much greater increase produced by EGF and FGF2 treatment. The
      number of BrdU + nestin double-labeled cells was larger than that of BrdU +
      ionized calcium-binding adapter molecule-1 (Iba1), BrdU + glial fibrillary acidic
      protein (GFAP), or BrdU + highly polysialylated neural cell adhesion molecule
      (PSA-NCAM) double-labeled cells, but none expressed neuronal nuclear antigen
      (NeuN). On further analysis of the gray matter of Tg mice, the number of BrdU +
      nestin and BrdU + PSA-NCAM double-labeled cells increased more in the ventral
      horns than the dorsal horns, which was again greatly enhanced by EGF and FGF2
      treatment. Because neural precursor cells reside close to the ependyma of central
      canal, the present study suggests that proliferation and migration of neural
      precursor cells to the ventral horns is greatly activated in symptomatic Tg mice
      and is further enhanced by EGF and FGF2 treatment and, furthermore, that the
      neural precursor cells preferentially differentiate into neuronal precursor cells
      instead of astrocytes in Tg mice with EGF and FGF2 treatment.

PMID- 16902997
TI  - Role of phosphorylation of ERK in induction and maintenance of LTP of the C-fiber
      evoked field potentials in spinal dorsal horn.
AB  - Previous works have shown that activation of extracellular signal-regulated
      kinase (ERK)/cAMP response element binding protein (CREB) pathway is essential
      for long-term potentiation (LTP) in hippocampus. In the present study, the role
      of the ERK/CREB pathway in LTP of C-fiber evoked field potentials in spinal
      dorsal horn, which is relevant to pathologic pain, was investigated in adult
      rats. Western blotting analysis showed that the protein level of phosphorylated
      ERK (p-ERK) in ipsilateral spinal dorsal horn was transiently increased after LTP
      induction, starting at 15 min and returning to control at 60 min after tetanic
      stimulation and that the protein level of p-CREB increased at 30 min, persisting
      for at least 3 hr after LTP induction. Double immunofluorescence staining showed
      that p-ERK and p-CREB were only located in neurons but not in glial cells in the
      spinal dorsal horn after LTP induction. More importantly, we found that spinal
      application of PD 98059 (100 microM), a selective MEK inhibitor, at 30 min before
      tetanic stimulation blocked LTP induction and prevented the increase in p-ERK and
      p-CREB in spinal dorsal horn. When applied 15 min after LTP induction, PD98059
      reversed established LTP. The drug, however, did not affect the spinal LTP, when
      applied at 30 min after LTP. Our results suggested that activation of ERK/CREB
      pathway in spinal dorsal neurons is necessary for induction and maintenance of
      long-term potentiation of the C-fiber evoked field potentials.

PMID- 16902998
TI  - Murine neocortical histogenesis is perturbed by prenatal exposure to low doses of
      Bisphenol A.
AB  - Bisphenol A (BPA) has been shown to disrupt thyroid hormone function. We
      therefore studied whether prenatal exposure to low-doses of BPA affects the
      morphology and the expression of some genes related to brain development in the
      murine fetal neocortex. Pregnant mice were injected subcutaneously with 20
      microg/kg of BPA daily from embryonic day 0 (E0). Control animals received
      vehicle alone. For evaluating cell proliferation, neuronal differentiation and
      migration, bromodeoxyuridine (BrdU) was injected intraperitoneally into pregnant
      mice with various regimens and the brains were processed for
      immunohistochemistry. The total RNA was extracted from the embryonic
      telencephalon at various embryonic stages. The BrdU-labeled cells examined 1 hour
      after BrdU injection showed no differences between the BPA-treated and control
      groups (n = 10, each), which indicated that the proliferation of precursor cells
      was not affected. The BrdU-labeled cells, analysed 2 days after BrdU injection,
      were decreased in the ventricular zone of BPA-treated mice at E14.5 and E16.5,
      whereas they were increased in the cortical plate at E14.5 as compared with those
      in control mice (n = 10, each). Furthermore, the expression of Math3, Ngn2, Hes1,
      LICAM, and THRalpha was significantly upregulated at E14.5 in the BPA-treated
      group. These results suggested that BPA might disrupt normal neocortical
      development by accelerating neuronal differentiation/migration.

PMID- 16902999
TI  - Nicotine reverses adult-onset hypothyroidism-induced impairment of learning and
      memory: Behavioral and electrophysiological studies.
AB  - Nicotine alleviates cognitive impairment associated with a variety of health
      conditions. We examined the effect of chronic nicotine treatment on adult-onset
      hypothyroidism-induced impairment of learning and memory in rats. Hypothyroidism
      was induced by surgical removal of thyroid glands (thyroidectomy). One month
      later, chronic nicotine treatment (1 mg/kg sc, twice/day) was instituted for 4-6
      weeks. Test of hippocampus-dependent spatial learning and memory in the radial
      arm water maze showed that hypothyroidism impaired learning as well as short-term
      and long-term memory retention. Chronic nicotine treatment reversed the
      hypothyroidism-induced learning and memory impairment. In normal rats, chronic
      nicotine treatment had no effect on learning and memory. Extracellular recordings
      from the CA1 region of anesthetized hypothyroid rats showed severe reduction of
      both early-phase and late-phase long-term potentiation (LTP) magnitude, which was
      reversed in nicotine-treated hypothyroid rats. These results show that chronic
      nicotine treatment prevents hypothyroidism-induced impairment of spatial
      cognition and LTP.

PMID- 16903000
TI  - Green's function study of the one-electron and shake-up ionization spectra of
      unsaturated hydrocarbon cage compounds.
AB  - The valence one-electron and shake-up ionization spectra of stella-2,6-diene,
      stella-2,6-dione, bicyclo-[2.2.2]-octane-2,5-dione, and bicyclo-[2.2.1]-heptane
      2,5-dione have been exhaustively studied, up to the double ionization threshold
      and beyond, by means of one-particle Green's function theory. This study is based
      on calculations employing the outer-valence Green's function and the third-order
      algebraic diagrammatic construction schemes, along with a variety of basis sets.
      A comparison is made with available ultraviolet (He I) photoelectron and (e, 2e)
      electron-impact ionization spectra, with main focus on the identification of
      spectral fingerprints for cyclic strains and through-bond pi-conjugation. As a
      byproduct, our results demonstrate that it is impossible to reliably assign
      complex (e, 2e) ionization spectra by resorting only to Hartree-Fock or Kohn-Sham
      orbital energies and to the related electron momentum distributions.

PMID- 16903001
TI  - Ab initio QM/MM dynamics of H3O+ in water.
AB  - A molecular dynamics (MD) simulation based on a combined ab initio quantum
      mechanics/molecular mechanics (QM/MM) method has been performed to investigate
      the solvation structure and dynamics of H3O+ in water. The QM region is a sphere
      around the central H3O+ ion, and contains about 6-8 water molecules. It is
      treated at the Hartree-Fock (HF) level, while the rest of the system is described
      by means of classical pair potentials. The Eigen complex (H9O4+) is found to be
      the most prevalent species in the aqueous solution, partly due to the selection
      scheme of the center of the QM region. The QM/MM results show that the Eigen
      complex frequently converts back and forth into the Zundel (H5O2+) structure.
      Besides the three nearest-neighbor water molecules directly hydrogen-bonded to
      H3O+, other neighbor waters, such as a fourth water molecule which interacts
      preferentially with the oxygen atom of the hydronium ion, are found occasionally
      near the ion. Analyses of the water exchange processes and the mean residence
      times of water molecules in the ion's hydration shell indicate that such next
      nearest neighbor water molecules participate in the rearrangement of the hydrogen
      bond network during fluctuative formation of the Zundel ion and, thus, contribute
      to the Grotthuss transport of the proton.

PMID- 16903002
TI  - Effect of particle size based separation of milled corn stover on AFEX
      pretreatment and enzymatic digestibility.
AB  - Particle size and compositional variance are found to have a substantial
      influence on ammonia fiber explosion (AFEX) pretreatment and enzymatic hydrolysis
      of lignocellulosic biomass. Corn stover was milled and fractionated into particle
      sizes of varying composition. The larger particle size fractions (rich in corn
      cob and stalk portions) were found to be more recalcitrant to hydrolysis compared
      to the smaller size fractions (rich in leaves and husk portion). Electron
      spectroscopy for chemical analysis (ESCA) and Fourier transform infrared
      spectroscopy (FTIR) were used for biomass surface and bulk compositional
      analysis, respectively. The ESCA results showed a 15-30% decrease in the O/C
      (oxygen to carbon) ratio after the pretreatment indicating an increase in the
      hydrophobic nature of biomass surface. FTIR results confirmed cleavage of the
      lignin-carbohydrate complex (LCC) for the AFEX-treated fractions. The
      spectroscopic results indicate the extraction of cleaved lignin phenolic
      fragments and other cell wall extractives to the biomass surface upon AFEX. Water
      washing of AFEX-treated fractions removed some of the hydrophobic extractives
      resulting in a 13% weight loss (dry weight basis). Phenolic content of wash
      stream was evaluated by the modified Prussian blue (MPB) method. Removal of ligno
      phenolic extractives from the AFEX-treated biomass by water washing vastly
      improved the glucan conversion as compared to the unwashed samples. Reduction in
      substrate particle size was found to affect the AFEX process and rate of
      hydrolysis as well. Implications of the stover particle size, composition, and
      inhibitory role of the phenolic fragments on an integrated biorefinery are
      discussed.

PMID- 16903003
TI  - Multivariate time-to-event analysis of multiple adverse events of drugs in
      integrated analyses.
AB  - In each clinical trial the statistical evaluation of adverse events (AEs) is a
      major part of standard safety analyses. However, the analyses of AEs usually lack
      from adequately accounting for the occurrence of multiple, different AEs.
      Furthermore, predictive variables other than treatment such as age, sex and
      concomitant medication are often ignored. These issues can be addressed by the
      Cox regression as introduced by Andersen and Gill and Wei et al. A further issue
      arises from the fact that an ordered programme of studies is conducted during
      clinical testing of pharmaceutical drugs. In this paper, we therefore discuss a
      stratified multivariate Cox regression model that can be used in integrated
      summaries of safety. We derive partial maximum likelihood estimators of the model
      parameters which can be shown to be consistent and asymptotically normally
      distributed. Mainly based on a sandwich estimator of their covariance matrix
      several test statistics are proposed that can be used to test various null
      hypotheses on the underlying parameters. Their asymptotic null distributions are
      given. The benefit of this survival time approach for analysing AEs is
      illustrated by evaluating symptoms of common cold from the database of a clinical
      development project.

PMID- 16903004
TI  - Ellis Samols.

PMID- 16903005
TI  - Proceedings of the 15th International Conference on Oral Chelation (ICOC) in the
      Treatment of Thalassaemia and other Diseases, part 2. Taichung, Taiwan, April 22
      26, 2005.

PMID- 16903007
TI  - MRI outcomes in AS patients after two years of etanercept therapy.

PMID- 16903006
TI  - Ethylene biology: A tribute to Edward C. Sisler.

PMID- 16903008
TI  - Salvage radical prostatectomy is second chance of cure.

PMID- 16903009
TI  - Red-algae derivative could be useful adjunct to HPV vaccine.

PMID- 16903010
TI  - [Pseudoaneurysm of splenic artery as complication of pancreatitis].

PMID- 16903012
TI  - Kidney tumours excel at evasion.

PMID- 16903011
TI  - Perioperative chemotherapy for gastro-oesophageal cancer.

PMID- 16903013
TI  - New protein implicated in survival of breast tumour cells.

PMID- 16903014
TI  - Abstracts of the Cardiac Society of Australia and New Zealand Annual Meeting and
      the International Society for Heart Research Annual Meeting, 4-7 August 2006,
      Canberra, Australia.

PMID- 16903016
TI  - Health care reform.

PMID- 16903017
TI  - [Brain infarction due to polycythemia as first indication of renal cell
      carcinoma].

PMID- 16903018
TI  - Global leprosy situation, 2006.

PMID- 16903019
TI  - Inhaled corticosteroids and children.

PMID- 16903020
TI  - Imatinib and altered bone and mineral metabolism.

PMID- 16903021
TI  - Genetic non-discrimination, privacy and property rights.

PMID- 16903022
TI  - Balancing pills and patents: intellectual property and the HIV/AIDS crisis.

PMID- 16903023
TI  - Human property: threat or saviour?

PMID- 16903024
TI  - Research on human embryos, stem cells and cloning -- one year since the passing
      of Australian federal legislation: Australia around the world and back again.

PMID- 16903025
TI  - European Directive on the Legal Protection of Biotechnological Inventions: scope,
      status and controversies in a nutshell.

PMID- 16903026
TI  - The intrinsic value of human life: a critique of Life's Dominion.

PMID- 16903027
TI  - [Guideline of intensive care unit design and management of China (2006)].

PMID- 16903028
TI  - The international regulation of genetically modified organisms: importing caution
      into the U.S. food supply.

PMID- 16903029
TI  - Health and food safety: the benefits of Bt-corn.

PMID- 16903030
TI  - Old customs, ancient lore: the development of custom device law through neglect.

PMID- 16903031
TI  - The Food and Drug Administration's regulation of risk disclosure for implantable
      cardioverter defibrillators: has technology outpaced the Agency's regulatory
      framework?

PMID- 16903032
TI  - Merck v. Integra: Supreme Court permits use of patented compounds to obtain Food
      and Drug Administration approvals.

PMID- 16903033
TI  - Your business in court--2005.

PMID- 16903034
TI  - The Food and Drug Administration's use of postmarketing (Phase IV) study
      requirements: exception to the rule?

PMID- 16903035
TI  - Not as easy as it may appear: using radio frequency identification technology to
      fulfill the Prescription Drug Marketing Act's elusive pedigree requirement.

PMID- 16903036
TI  - Molecular analysis of colonic transformation in the ileum after total colectomy
      in rats.
AB  - BACKGROUND: Colonic transformation is thought to be a phenotypic alteration in
      the ileum after total colectomy (TC) but has not been well addressed at the
      molecular level. We previously demonstrated roles of aldosterone in enhancement
      of ileal sodium absorption after TC. However, the significance of aldosterone in
      intestinal adaptation has been unknown. METHODS: Rat epithelial gene expression
      was compared between the ileum and distal colon by complementary DNA microarray.
      Genes were categorized into "colonic," "common," and "ileal" genes according to
      signal intensity. Ileal gene expressions in (1) the control and TC rats and (2)
      the control and aldosterone-infused rats were compared to detect altered genes or
      to assess the role of aldosterone in intestinal adaptation. Differential
      expression of MUC3 and lysozyme was confirmed by quantitative reverse
      transcriptase-polymerase chain reaction. RESULTS: A total of 6109 genes were
      categorized into "colonic," "common," or "ileal" gene pools. A comparison of the
      control and TC rats yielded 82 and 91 genes that were induced and suppressed in
      the ileum after TC, respectively. Thirty-five percent of them were associated
      with colonlike transformation (ie, the induction of colonic genes or the
      suppression of ileal genes). The expressions of MUC3 and lysozyme messenger RNAs
      were enhanced significantly in the TC ileum, compared with the control. In
      comparison, aldosterone infusion modulated a total of only 21 genes in the ileum.
      CONCLUSION: Those data demonstrate that altered gene expression after TC is, in
      part, characterized by colonlike transformation. Furthermore, circulating
      aldosterone appears to play a part in the altering and/or adapting of gene
      expression in intestinal epithelium.

PMID- 16903037
TI  - Sports medicine: the last 100 years.

PMID- 16903038
TI  - Overwinter mass loss of snowshoe hares in the Yukon: starvation, stress,
      adaptation or artefact?
AB  - 1. Overwinter mass loss can reduce energetic requirements in mammals (Dehnel's
      phenomenon). Alternatively, mass loss can result from food limitation or high
      predation risk. 2. We use data from fertilizer, food-supplementation and predator
      exclusion experiments in the Yukon during a population cycle from 1986 to 1996 to
      test the causes of overwinter mass loss by snowshoe hares (Lepus americanus). In
      all years, some hares on control sites gained mass overwinter. During the
      increase phase the majority gained mass, but in all other phases the majority
      lost mass. 3. Snowshoe hares weighing <1000 g in autumn always gained mass
      overwinter, as did the majority that weighed 1000-1400 g. Hares weighing >1800 g
      in autumn usually lost mass. 4. Snowshoe hares on the predator-exclosure + food
      site gained mass overwinter in all years. Hares on the food-supplementation sites
      lost mass during the decline but gained mass in all other phases. Fertilization
      had little effect on mass dynamics. 5. Snowshoe hares were more likely to lose
      mass during winters with low survival rates. Snowshoe hares on the predator
      exclosure treatments were more likely to gain mass than were hares on control
      sites. 6. Overwinter mass loss was correlated with maximum snow depth. At
      equivalent snow depths, hares on food-supplemented areas lost 98 g (+/- 14.6 SE)
      less on average than hares on the controls and predator-exclosure treatment. 7.
      Bone-marrow fat was related to body mass and cause of death. Small hares had the
      lowest marrow fat. Hares killed by humans had higher marrow fat than those killed
      by predators; hares that simply died had the lowest marrow fat. Hares on food
      supplemented sites had the highest kidney and marrow fat. 8. Overwinter-mass loss
      for snowshoe hares is explained interactively by winter conditions, food supply,
      predation risk and autumn mass. Some snowshoe hares lost mass overwinter in all
      years and on all treatments, suggesting that reducing body mass may facilitate
      survival, especially in cases where foraging costs are high energetically or
      increase predation risk.

PMID- 16903039
TI  - Quantifying the influence of sociality on population structure in bottlenose
      dolphins.
AB  - 1. The social structure of a population plays a key role in many aspects of its
      ecology and biology. It influences its genetic make-up, the way diseases spread
      through it and the way animals exploit their environment. However, the
      description of social structure in nonprimate animals is receiving little
      attention because of the difficulty in abstracting social structure from the
      description of association patterns between individuals. 2. Here we focus on
      recently developed analytical techniques that facilitate inference about social
      structure from association patterns. We apply them to the population of
      bottlenose dolphins residing along the Scottish east coast, to detect the
      presence of communities within this population and infer its social structure
      from the temporal variation in association patterns between individuals. 3. Using
      network analytical techniques, we show that the population is composed of two
      social units with restricted interactions. These two units seem to be related to
      known differences in the ranging pattern of individuals. By examining social
      structuring at different spatial scales, we confirm that the identification of
      these two units is the result of genuine social affiliation and is not an
      artefact of their spatial distribution. 4. We also show that the structure of
      this fission-fusion society relies principally on short-term casual acquaintances
      lasting a few days with a smaller proportion of associations lasting several
      years. These findings highlight how network analyses can be used to detect and
      understand the forces driving social organization of bottlenose dolphins and
      other social species.

PMID- 16903040
TI  - Multiple predator effects in an intertidal food web.
AB  - 1. We examined the effects of multiple predators from an intertidal boulder food
      web to test whether and how three different predator species affected the
      survival of a small amphipod species. 2. Predators were chosen because they
      differ in their foraging mode, two feeding at the bottom and in benthic refuges
      (nemertean and shrimp) and one in the water-column (juveniles of a fish). 3.
      Mortality of amphipods was not affected by nemerteans, but was high in the
      presence of shrimp or fish. Highest mortalities were observed in predator
      combinations that contained both shrimp and fish. Amphipods responded to shrimp
      by escaping into the water column, while they avoided fish by remaining in the
      refuge. We conclude that predator-specific defence causes conflicts for prey when
      both shrimp and fish are present. 4. Comparing observed effects of multiple
      predators with expected effects revealed risk enhancement for the shrimp + fish
      combination. A comparison of different predictive models revealed that the
      multiplicative model was most appropriate, although additive models may work well
      under certain conditions. 5. Based on known consumption-ranges of the predators
      used, we conclude that nemerteans were saturated with prey while fish were far
      from their saturation point. A predator's functional response curve (prey
      consumption in relation to prey abundance) determines its impact on prey
      populations. This knowledge appears essential in order to predict whether prey
      organisms face risk enhancement, risk reduction or additive effects of multiple
      predators.

PMID- 16903041
TI  - Sexually transmitted disease epidemics in a natural insect population.
AB  - 1. The epidemiology of sexually transmitted diseases (STDs) in human and
      domesticated populations is well documented. However, there has been less study
      of STDs in natural populations. 2. We investigated STD dynamics in the model
      system involving a host from the most speciose group of animals: the insects. We
      investigated temporal variation in the prevalence of the sexually transmitted
      mite Coccipolipus hippodamiae on its ladybird host, Adalia bipunctata. 3. Field
      surveys over two seasons showed a repeated pattern of a profound epidemic in the
      overwintered cohort and a later prevalence decline. 4. In order to understand the
      key factors in the dynamics of this system we studied the phenology of the host
      and simulated parasite dynamics in the overwintered cohort using a model with
      within-sex homogeneity in mating rate and field-measured parameter values. The
      similarity of natural and simulation prevalence levels allowed us to carry out
      sensitivity analysis and hence to identify the key determinants of the dynamics.
      5. The observed pattern of periodic extreme prevalence combined with system
      persistence probably results from time lags in host recruitment and widespread
      promiscuity. 6. Our findings improve our understanding of STDs in natural
      populations and illustrate the importance of examining seasonality and time
      delays in population dynamics in order to fully understand the characteristics of
      natural populations and their parasites.

PMID- 16903042
TI  - Parasitism shaping host life-history evolution: adaptive responses in a marine
      gastropod to infection by trematodes.
AB  - 1. Variation in life-history strategies among conspecific populations indicates
      the action of local selective pressures; recently, parasitism has been suggested
      as one of these local forces. 2. Effects of trematode infections on reproductive
      effort, juvenile growth, size at maturity and susceptibility were investigated
      among different natural populations of the marine gastropod Zeacumantus
      subcarinatus, Sowerby 1855. 3. Reproductive effort was not higher in uninfected
      snails from populations experiencing a high trematode prevalence, but females
      from high prevalence populations produced significantly larger offspring compared
      with their conspecifics from other populations. 4. Juvenile growth rate was
      significantly higher in laboratory-raised snails originating from females in a
      high prevalence population compared with other populations. 5. Size at maturity,
      determined by the appearance of functional gonads, was significantly and
      negatively related to trematode prevalence, and positively related to mean snail
      size, across 10 populations in the study area. 6. There was no evidence of
      different host resistance against trematodes in sentinel snails from high and low
      prevalence populations exposed to the same infection pressure in the field. 7.
      Our results strongly indicate that Z. subcarinatus adapt to trematodes by
      reaching maturity early, thereby maximizing their chance of reproducing in
      populations experiencing a high prevalence of infection by castrating trematodes.

PMID- 16903043
TI  - Periodic habitat loss alters the competitive coexistence between brown trout and
      bullheads in a small stream over 34 years.
AB  - 1. Changes in the population density of juvenile sea trout Salmo trutta L. and
      bullheads Cottus gobio L. were compared in a small stream over 34 years. Both
      species have a similar diet and obviously live in the same general habitat.
      Habitat loss was most marked in seven summer droughts: severest in 1976, 1983,
      1984, 1995, and less severe but followed by autumn droughts in 1969, 1989 and
      1993. The contrasting effects of habitat loss on the two species were examined.
      2. For both species, the Ricker curvilinear model significantly fit (P < 0.001)
      the relationship between initial egg density and survivor density for successive
      life stages, even though egg densities were much lower for bullheads than trout.
      These analyses provided evidence for density-dependent population regulation and
      also identified extreme outliers, most being for year-classes affected by summer
      droughts. 3. The variable effects of changes in habitable area (= % wettable area
      in sampling section) were quantified by using the residuals, each residual being
      the absolute value expressed as a percentage of the expected value from the
      Ricker curve. Significant relationships between the residuals and habitable area
      showed that habitat loss had a marked effect on survivor density, this being
      negative for 0+ and 1+ trout, and positive for 0+, 1+ and 2+/3+ bullheads. 4.
      Therefore, during periods of habitat loss in the summer months, bullhead density
      increased at the expense of trout density. Low flows and a decrease in wettable
      area were associated with a marked reduction in habitat quality for drift-feeding
      trout and an increase in habitat quality, and perhaps also quantity, for benthic
      feeding bullheads. This case study shows that, during a major perturbation, the
      relationship between the densities of two species can change markedly in favour
      of the less numerous species. The competitive coexistence between the two species
      is therefore a dynamic process that changes through time with periodic changes in
      the environment.

PMID- 16903044
TI  - Understanding ecosystem dynamics for conservation of biota.
AB  - 1. Ecosystems have higher-order emerging properties that can affect the
      conservation of species. We identify some of these properties in order to
      facilitate a better understanding of them. 2. Nonlinear, indirect effects of food
      web interactions among species can produce counterintuitive changes in
      populations. 3. Species differ in their roles and linkages with other species in
      the system. These roles are a property of the system. Such differences in roles
      influence how we conserve individual species. 4. Ecosystems operate at a
      multitude of interacting spatial and temporal scales, which together structure
      the system and affect the dynamics of individual populations. 5. Disturbance also
      structures an ecosystem, producing both long-term slow changes and sudden shifts
      in ecosystem dynamics. 6. Ecosystems therefore can have multiple states,
      determined both by disturbance regimes and biotic interactions. Conservation
      should recognize a possible multiplicity of natural states while avoiding
      aberrant (human-induced) states. 7. Ecosystem processes are influenced by the
      composition of the biota they contain. Disturbances to the biota can distort
      processes and functions, which in turn can endanger individual species. 8. The
      goal of ecosystem conservation is the long-term persistence of the biota in the
      system. There are two paradigms: community-based conservation (CBC) and protected
      area conservation. Both have their advantages but neither is sufficient to
      protect the biota on its own. 9. CBC is required to conserve the majority of the
      world's biota not included in protected areas. However, current CBC methods
      favour a few idiosyncratic species, distort the species complex, and ignore the
      majority. More comprehensive methods are required for this approach to meet the
      goal of ecosystem conservation. 10. Protected areas are essential to conserve
      species unable to coexist with humans. They also function as ecological baselines
      to monitor the effects of humans on their own ecosystems. 11. However, protected
      areas suffer from loss of habitat through attrition of critical areas. Thus,
      renewal (addition) of habitat is required in order to achieve the long-term
      persistence of biota in functioning ecosystems. Identification of minimum habitat
      areas and restoration of ecosystems become two major priorities for future
      research.

PMID- 16903045
TI  - Climate and spatio-temporal variation in the population dynamics of a long
      distance migrant, the white stork.
AB  - 1. A central question in ecology is to separate the relative contribution of
      density dependence and stochastic influences to annual fluctuations in population
      size. Here we estimate the deterministic and stochastic components of the
      dynamics of different European populations of white stork Ciconia ciconia. We
      then examined whether annual changes in population size was related to the
      climate during the breeding period (the 'tap hypothesis' sensu Saether,
      Sutherland & Engen (2004, Advances in Ecological Research, 35, 185 209) or during
      the nonbreeding period, especially in the winter areas in Africa (the 'tube
      hypothesis'). 2. A general characteristic of the population dynamics of this long
      distance migrant is small environmental stochasticity and strong density
      regulation around the carrying capacity with short return times to equilibrium.
      3. Annual changes in the size of the eastern European populations were correlated
      by rainfall in the wintering areas in Africa as well as local weather in the
      breeding areas just before arrival and in the later part of the breeding season
      and regional climate variation (North Atlantic Oscillation). This indicates that
      weather influences the population fluctuations of white storks through losses of
      sexually mature individuals as well as through an effect on the number of
      individuals that manages to establish themselves in the breeding population.
      Thus, both the tap and tube hypothesis explains climate influences on white stork
      population dynamics. 4. The spatial scale of environmental noise after accounting
      for the local dynamics was 67 km, suggesting that the strong density dependence
      reduces the synchronizing effects of climate variation on the population dynamics
      of white stork. 5. Several climate variables reduced the synchrony of the
      residual variation in population size after accounting for density dependence and
      demographic stochasticity, indicating that these climate variables had a
      synchronizing effect on the population fluctuations. In contrast, other climatic
      variables acted as desynchronizing agents. 6. Our results illustrate that
      evaluating the effects of common environmental variables on the spatio-temporal
      variation in population dynamics require estimates and modelling of their
      influence on the local dynamics.

PMID- 16903046
TI  - Dispersal-related life-history trade-offs in a butterfly metapopulation.
AB  - 1. Recent studies on butterflies have documented apparent evolutionary changes in
      dispersal rate in response to climate change and habitat change. These studies
      often assume a trade-off between dispersal rate (or flight capacity) and
      reproduction, which is the rule in wing-dimorphic species but might not occur
      equally in wing-monomorphic species such as butterflies. 2. To investigate the
      relationship between dispersal rate and fecundity in the Glanville fritillary
      butterfly Melitaea cinxia we recorded lifetime individual movements, matings,
      ovipositions, and maximal life span in a large (32 x 26 m) population cage in the
      field. Experimental material was obtained from 20 newly established and 20 old
      local populations within a large metapopulation in the Aland Islands in Finland.
      3. Females of the Glanville fritillary from newly established populations are
      known to be more dispersive in the field, and in the cage they showed
      significantly greater mobility, mated earlier, and laid more egg clutches than
      females from old populations. The dispersive females from new populations
      exhibited no reduced lifetime fecundity in the cage, but they had a shorter
      maximal life span than old-population females. 4. These results challenge the
      dispersal-fecundity trade-off for nonmigratory butterflies but instead suggest a
      physiological trade-off between high metabolic performance and reduced maximal
      life span. High metabolic performance may explain high rates of dispersal and
      oviposition in early life. 5. In fragmented landscapes, an ecological trade-off
      exists between being more dispersive and hence spending more time in the
      landscape matrix vs. having more time for reproduction in the habitat. We
      estimate with a dispersal model parameterized for the Glanville fritillary that
      the lifetime egg production is 4% smaller on average in the more dispersive
      butterflies in a representative landscape, with much variation depending on
      landscape structure in the neighbourhood of the natal patch, from--26 to 45% in
      the landscape analysed in this paper.

PMID- 16903047
TI  - Predator functional response and prey survival: direct and indirect interactions
      affecting a marked prey population.
AB  - 1. Predation plays an integral role in many community interactions, with the
      number of predators and the rate at which they consume prey (i.e. their
      functional response) determining interaction strengths. Owing to the difficulty
      of directly observing predation events, attempts to determine the functional
      response of predators in natural systems are limited. Determining the forms that
      predator functional responses take in complex systems is important in advancing
      understanding of community interactions. 2. Prey survival has a direct
      relationship to the functional response of their predators. We employed this
      relationship to estimate the functional response for bald eagle Haliaeetus
      leucocepalus predation of Canada goose Branta canadensis nests. We compared
      models that incorporated eagle abundance, nest abundance and alternative prey
      presence to determine the form of the functional response that best predicted
      intra-annual variation in survival of goose nests. 3. Eagle abundance, nest
      abundance and the availability of alternative prey were all related to predation
      rates of goose nests by eagles. There was a sigmoidal relationship between
      predation rate and prey abundance and prey switching occurred when alternative
      prey was present. In addition, predation by individual eagles increased as eagle
      abundance increased. 4. A complex set of interactions among the three species
      examined in this study determined survival rates of goose nests. Results show
      that eagle predation had both prey- and predator-dependent components with no
      support for ratio dependence. In addition, indirect interactions resulting from
      the availability of alternative prey had an important role in mediating the rate
      at which eagles depredated nests. As a result, much of the within-season
      variation in nest survival was due to changing availability of alternative prey
      consumed by eagles. 5. Empirical relationships drawn from ecological theory can
      be directly integrated into the estimation process to determine the mechanisms
      responsible for variation in observed survival rates. The relationship between
      predator functional response and prey survival offers a flexible and robust
      method to advance our understanding of predator-prey interactions in many complex
      natural systems where prey populations are marked and regularly visited.

PMID- 16903048
TI  - How to test different density-dependent fecundity hypotheses in an increasing or
      stable population.
AB  - 1. We report on a simulation study of increasing and stable populations working
      under two different hypotheses of density dependence of fecundity: the habitat
      heterogeneity hypothesis (HHH) and the individual adjustment hypothesis (IAH).
      Our aim is to find critical differences between the two regulatory hypotheses in
      natural populations. 2. Populations under HHH show a strong negative relationship
      between fecundity and the coefficient of variation of fecundity. We also found a
      strong negative relationship between fecundity and skewness, demonstrating that,
      as fecundity decreases, the form of the distribution of brood sizes changes,
      being more left-skewed due to more territories failing to produce any offspring.
      3. This strong relationship was found only in the simulations of populations
      under HHH; whether increasing or stable, and under different ratios of good: poor
      territories and different population sizes. In contrast, no relationship between
      mean fecundity and skewness was found among simulations under IAH. 4. Populations
      under IAH also showed a significant relationship between mean fecundity and the
      coefficient of variation of fecundity, but with a lower slope than in populations
      under HHH. 5. In conclusion, skewness was found to be an adequate critical test
      that showed significant and strong relationships with mean fecundity only in
      populations under HHH, whether increasing or stable. This test is useful for
      species with a discrete distribution of offspring with a small number of integer
      categories, including most of the bird and mammal species.

PMID- 16903049
TI  - An experimental test of the effects of food resources and hydraulic refuge on
      patch colonization by stream macroinvertebrates during spates.
AB  - 1. The passive or active movement of organisms between habitat patches plays
      important roles in achieving ecosystem resilience to disturbance and long-term
      control of population levels. However, causal mechanisms of disturbance-induced
      movements of mobile biota across heterogeneous habitat patches at a relatively
      short time-scale are little understood. 2. We experimentally tested the effects
      of food resource values on macroinvertebrate colonization of hydraulic refugia
      from spates in a second-order creek. Experimental cages were colonized by
      macroinvertebrates with combinations of resource types (natural or polyester
      leaves), and extent of exposure to stream flow (exposed to or sheltered from
      current); one half of each set was collected before and after a spate. This
      experiment was repeated over three spates of varying magnitude and seasonal
      contexts. 3. Pre-spate colonization was consistently greater for the cages with
      natural leaves relative to artificial leaves regardless of the extent of flow
      exposure. Two autumn spates with relatively low and stable antecedent flow
      conditions caused large movements of organic matter and macroinvertebrates across
      the stream, showing community-level accumulations into hydraulically sheltered
      patches independent of food treatment. The smallest spate with high and variable
      antecedent flows during winter resulted in negligible responses, which we
      interpret to be a result of depletion of easily transportable organic matter and
      organisms. 4. Two detritivorous taxa, the mayfly Paraleptophlebia spp. and
      stonefly Despaxia augusta (Banks) were the most responsive to autumn spates, and
      had disproportionately higher colonization rates of cages when provided with
      natural leaves during the largest autumn spate. Preferential settlement in food
      enriched hydraulic refugia was attributable to taxon-specific mobility related to
      efficient acquisition of detritus resource, whose availability varies spatially
      and temporally. 5. Our findings suggest (1) detritivorous macroinvertebrate
      colonization of hydraulic refugia can be influenced by hydraulic controls as well
      as food resource value, and (2) pre-spate environmental conditions in terms of
      resource distribution and availability may pre-condition organisms'
      susceptibility to spates and also affect refugium usage, at least in food
      limited, detritus-based stream systems.

PMID- 16903050
TI  - Grasshopper ontogeny in relation to time constraints: adaptive divergence and
      stasis.
AB  - 1. Life history theory generally predicts a trade-off between shortjuvenile
      development and large adult size, assuming invariant growth rates within species.
      This pivotal assumption has been explicitly tested in few organisms. 2. We
      studied ontogeny in 13 populations of Omocestus viridulus grasshoppers under
      common garden conditions. High-altitude populations, facing short growing seasons
      and thus seasonal time constraints, were found to grow at a similar rate to low
      altitude conspecifics. 3. Instead, high-altitude grasshoppers evolved faster
      development, and the correlated change in body size led to an altitudinal size
      cline mediating a trade-off with female fecundity. 4. An additional juvenile
      stage occurred in low- but not high-altitude females. This difference is probably
      due to the evolution of lowered critical size thresholds in high-altitude
      grasshoppers to accelerate development. 5. We found a strikingly lower growth
      rate in males than females that we interpret as the outcome of concurrent
      selection for protandry and small male size. 6. Within populations, large
      individuals developed faster than small individuals, suggesting within-population
      genetic variation in growth rates. 7. We provide evidence that different time
      constraints (seasonal, protandry selection) can lead to different evolutionary
      responses in intrinsic growth, and that correlations among ontogenetic traits
      within populations cannot generally be used to predict life history adaptation
      among populations. Moreover, our study illustrates that comparisons of
      ontogenetic patterns can shed light on the developmental basis underlying
      phenotypic evolution.

PMID- 16903051
TI  - A spatially explicit approach to estimating species occupancy and spatial
      correlation.
AB  - 1. Understanding and predicting the form of species distributions, or occupancy
      patterns, is fundamental to macroecology and is dependent on the identification
      of scaling relationships that underlie the patterns observed. 2. Occupancy
      abundance models based on the negative binomial distribution and Taylor's power
      law are spatially implicit, rather than explicit, as they include no information
      on the relative positions of individuals. Here we present a spatially explicit
      model, the spatial scaling occupancy (SSO) model, to estimate species occupancy
      and spatial correlation, based on join-count statistics, or a pair approximation,
      approach. This model provides a spatially explicit description of species range
      size and aspects of range structure. 3. Occupancy data from Drosophilidae species
      inhabiting a decaying fruit mesocosm were used to test the SSO model. Predictions
      from the spatially implicit and explicit models were largely equally accurate.
      The SSO model is thus more efficient as it is less data demanding, and more
      informative as it provides an estimation of spatial correlation. 4. The results
      also showed that species distribution patterns differ when examined with
      spatially implicit vs. explicit approaches; the scaling relationship between
      occupancy and local density identifies a focal grain for studying the scale
      dependent nature of ecological relationships; and the longer the length of the
      sample edge, the higher the occupancy observed under conditions of spatial
      aggregation. 5. The SSO model presents a step towards a general scaling model for
      occupancy, and demonstrates that the inclusion of spatially explicit information
      in macroecological models warrants further attention.

PMID- 16903052
TI  - Habitat selection by chironomid larvae: fast growth requires fast food.
AB  - 1. Sediments have been considered as a habitat, a cover from predators and a
      source of food, but also as a source of potential toxic compounds. Therefore, the
      choice of a suitable substrate is essential for the development of chironomids.
      2. For the midge Chironomus riparius (Meigen 1804) the growth rate of larvae has
      often been related to the food quality in sediments rather than to the amount of
      toxicants in the sediment. Both food quality and sediment-bound toxicants have
      been reported to determine the field distribution of chironomid larvae. 3. We
      therefore studied the habitat selection by C. riparius larvae of floodplain lake
      sediments, differing in both food quality and concentrations of sediment-bound
      toxicants. We offered the different sediments pairwise to the chironomid larvae
      in a choice experiment and their settlement in the paired sediments was
      determined after 10 days. 4. It was observed that larvae showed a clear
      preference for sediments with higher food quality, which also provided better
      growth conditions, and that the food quality overruled avoidance of the sediments
      with higher toxicant concentrations. 5. Our observations correspond with the
      persistence of this fast growing opportunistic chironomid species in organically
      enriched aquatic ecosystems independent of the contamination level.

PMID- 16903053
TI  - Small rodent winter survival: snow conditions limit access to food resources.
AB  - 1. In Fennoscandia during winter small rodents spend most of their time in the
      subnivean space, between the snow cover and the ground. The subnivean space is
      probably not a uniform habitat, but broken into accessible and inaccessible
      patches by ice covering the vegetation. This might reduce access to otherwise
      available food resources. 2. To test whether ice formations reduce access to food
      and thus limit winter survival of small rodents, we conducted an experiment where
      we increased subnivean space by adding corrugated aluminium sheets on the ground
      before onset of winter. The sheets prevented ice formation, thus mimicking
      natural occurring subnivean space, and providing more room for animals living in
      the subnivean space to forage. 3. During the experiment 142 Microtus oeconomus
      were passive induced transponder (PIT)-tagged, and a system consisting of fixed
      tube-shaped antennas and PIT-tag readers were used to provide data to analyse
      winter survival and individual subnivean space use. The extent of winter grazing
      was measured after snow melt by examining percentage area grazed. 4. The
      treatment resulted in increased survival which corresponded well with
      significantly higher space use and more grazing under the sheets. 5. Females
      showed a positive correlation between probability of survival and body mass while
      no such effect was observed in males. 6. The results suggest that the snow cover
      reduces survival in winter by physically enclosing the vegetation in ice and thus
      reducing access to otherwise available food resources. The amount of ice and its
      configuration might vary between years due to changing weather patterns. Our
      results offer a mechanistic explanation for variations in winter survival and
      suggest incorporating climate variables in future small rodent models. 7.
      Directional and long-term changes in climate might result in increased ice
      formation in the subnivean system. Such deterioration may lead to reduced winter
      survival and act by stabilizing population dynamics and dampening vole cyclicity.

PMID- 16903054
TI  - Intraguild indirect effects through trophic cascades between stream-dwelling
      fishes.
AB  - 1. To examine the strength and role of indirect effects through trophic cascades
      by omnivorous fish on algal biomass in streams, we introduced one of four fish
      species (ayu Plecoglossus altivelis altivelis, pike gudgeon Pseudogobio esocinus
      esocinus, Japanese dace Tribolodon hakonensis and pale chub Zacco platypus) in
      experimental pools. We also investigated the indirect effects of gudgeon, dace
      and chub on the growth of ayu. 2. We chose the four fish species across a
      continuum of omnivory. Ayu fed mainly on benthic algae, and gudgeon predominantly
      on invertebrates. Dace and chub fed on both algae and invertebrates, but dace
      preyed on invertebrates more than chub. 3. The presence of gudgeon, dace and chub
      reduced the number of algal-feeding invertebrates and increased the algal biomass
      through trophic cascades. Consequently, ayu growth rate over the experimental
      period in pools with one of the three fish species was 25.9-44.1 times greater
      than the growth rate in pools with only ayu. 4. The positive indirect effect on
      ayu growth was large for gudgeon and dace and small for chub, whereas the
      addition of ayu reduced ayu growth considerably due to intraspecific competition.
      5. The relative intensity of indirect effects on ayu growth through trophic
      cascades was predictable from the food overlap between ayu and the other fishes.
      However, the similar strength of indirect effects by gudgeon and dace that fed
      differently on algae and invertebrates suggests that feeding behaviour, prey
      preference and trait-mediated indirect interactions were also important in the
      prediction.

PMID- 16903055
TI  - Hunt warm, rest cool: bioenergetic strategy underlying diel vertical migration of
      a benthic shark.
AB  - 1. Diel vertical migration (DVM) is a widespread phenomenon among marine and
      freshwater organisms and many studies with various taxa have sought to understand
      its adaptive significance. Among crustacean zooplankton and juveniles of some
      fish species DVM is accepted widely as an antipredator behaviour, but little is
      known about its adaptive value for relatively large-bodied, adult predatory fish
      such as sharks. Moreover, the majority of studies have focused on pelagic forms,
      which raises the question of whether DVM occurs in bottom-living predators. 2. To
      investigate DVM in benthic predatory fish in the marine environment and to
      determine why it might occur we tracked movements of adult male dogfish
      (Scyliorhinus canicula) by short- and long-term acoustic and archival telemetry.
      Movement studies were complemented with measurements of prey abundance and
      availability and thermal habitat within home ranges. A thermal choice experiment
      and energy budget modelling was used to investigate trade-offs between foraging
      and thermal habitat selection. 3. Male dogfish undertook normal DVM (nocturnal
      ascent) within relatively small home ranges (-100 x 100 m) comprising along
      bottom movements up submarine slopes from deeper, colder waters occupied during
      the day into warmer, shallow prey-rich areas above the thermocline at night. Few
      daytime vertical movements occurred. Levels of activity were higher during the
      night above the thermocline compared to below it during the day indicating they
      foraged in warm water and rested in colder depths. 4. A thermal choice experiment
      using environmentally realistic temperatures supported the field observation that
      dogfish positively avoided warmer water even when it was associated with greater
      food availability. Males in laboratory aquaria moved into warm water from a
      cooler refuge only to obtain food, and after food consumption they preferred to
      rest and digest in cooler water. 5. Modelling of energy budgets under different
      realistic thermal-choice scenarios indicated dogfish adopting a 'hunt warm - rest
      cool' strategy could lower daily energy costs by just over 4%. Our results
      provide the first clear evidence that are consistent with the hypothesis that a
      benthic marine-fish predator utilizes DVM as an energy conservation strategy that
      increases bioenergetic efficiency.

PMID- 16903056
TI  - Effects of patch quality and network structure on patch occupancy dynamics of a
      yellow-bellied marmot metapopulation.
AB  - 1. The presence/absence of a species at a particular site is the simplest form of
      data that can be collected during ecological field studies. We used 13 years
      (1990-2002) of survey data to parameterize a stochastic patch occupancy model for
      a metapopulation of the yellow-bellied marmot in Colorado, and investigated the
      significance of particular patches and the influence of site quality, network
      characteristics and regional stochasticity on the metapopulation persistence. 2.
      Persistence of the yellow-bellied marmot metapopulation was strongly dependent on
      the high quality colony sites, and persistence probability was highly sensitive
      to small changes in the quality of these sites. 3. A relatively small number of
      colony sites was ultimately responsible for the regional persistence. However,
      lower quality satellite sites also made a significant contribution to long-term
      metapopulation persistence, especially when regional stochasticity was high. 4.
      The northern network of the marmot metapopulation was more stable compared to the
      southern network, and the persistence of the southern network depended heavily on
      the northern network. 5. Although complex models of metapopulation dynamics may
      provide a more accurate description of metapopulation dynamics, such models are
      data-intensive. Our study, one of the very few applications of stochastic patch
      occupancy models to a mammalian species, suggests that stochastic patch occupancy
      models can provide important insights into metapopulation dynamics using data
      that are easy to collect.

PMID- 16903057
TI  - Gonochorism vs. hermaphroditism: relationship between life history and fitness in
      three species of Ophryotrocha (Polychaeta: Dorvilleidae) with different forms of
      sexuality.
AB  - 1. The relationships between life history, fitness and sexuality, together with
      their ecological and evolutionary significance, has been analysed comparing the
      main life-history traits and demography in three closely related species
      belonging to the genus Ophryotrocha. The species are: the gonochoristic O.
      labronica, the simultaneous hermaphrodite O. diadema and the protandrous
      hermaphrodite O. puerilis. 2. Survivorship and reproductive data were collected
      weekly and were used to construct life tables and population projection matrices
      for each species and compare life-history characteristics. Elasticity, life-table
      response and decomposition analyses were performed to examine the relative
      contribution of fecundity and survivorship to differences in lamda between
      species. 3. The gonochoristic and hermaphroditic species differ in all the main
      life-history parameters and also in demographic characteristics. In particular
      the value of lamda, used commonly to express fitness, is markedly higher in the
      gonochoristic species while in terms of fitness simultaneous and sequential
      hermaphroditism are very similar. In the genus Ophryotrocha gonochorism currently
      represents the most widespread condition, being characteristic of the majority of
      the known species in the genus. 4. Given the demographic advantage ensured by
      gonochorism, it remains be understood why some species have retained simultaneous
      hermaphroditism and one has evolved a sequential type hermaphroditism; the most
      probable hypothesis is correlated with the density of the species in natural
      habitats.

PMID- 16903058
TI  - Effects of predation and dispersal on Mastomys natalensis population dynamics in
      Tanzanian maize fields.
AB  - 1. We investigate the effects of different levels of predation pressure and
      rodent dispersal on the population dynamics of the African pest rodent Mastomys
      natalensis in maize fields in Tanzania. 2. Three levels of predation risk were
      used in an experimental set-up: natural level (control), excluding predators by
      nets and attracting avian predators by nest boxes and perch poles. Because
      dispersal of the rodents could mask the predation pressure treatment effects,
      control and predator exclusion treatments were repeated with enclosed rodent
      populations. 3. Population growth during the annual population rise period was
      faster in the absence of predators and peak population size was higher, but
      otherwise dynamics patterns were similar for populations where predators had
      access or were attracted, indicating that compensatory mechanisms operate when
      rodents are exposed to high levels of predation risk. Reducing dispersal of
      rodents removed the effect of predation on population growth and peak size,
      suggesting that local predators may play a role in driving rodent dispersal, but
      have otherwise little direct effect on population dynamics.

PMID- 16903059
TI  - Distribution-wide effects of climate on population densities of a declining
      migratory landbird.
AB  - 1. Increases in global temperatures have created concern about effects of
      climatic variability on populations, and climate has been shown to affect
      population dynamics in an increasing number of species. Testing for effects of
      climate on population densities across a species' distribution allows for
      elucidation of effects of climate that would not be apparent at smaller spatial
      scales. 2. Using autoregressive population models, we tested for effects of the
      North Atlantic Oscillation (NAO) and the El Nino Southern Oscillation (ENSO) on
      annual population densities of a North American migratory landbird, the yellow
      billed cuckoo Coccyzus americanus, across the species' breeding distribution over
      a 37-year period (1966-2002). 3. Our results indicate that both the NAO and ENSO
      have affected population densities of C. americanus across much of the species'
      breeding range, with the strongest effects of climate in regions in which these
      climate systems have the strongest effects on local temperatures. Analyses also
      indicate that the strength of the effect of local temperatures on C. americanus
      populations was predictive of long-term population decline, with populations that
      were more negatively affected by warm temperatures experiencing steeper declines.
      4. Results of this study highlight the importance of distribution-wide analyses
      of climatic effects and demonstrate that increases in global temperatures have
      the potential to lead to additional population declines.

PMID- 16903060
TI  - Recruitment to a seabird population depends on environmental factors and on
      population size.
AB  - 1. A novel capture-mark-recapture (CMR) method was used to build a multistate
      model of recruitment by young birds to a breeding population of common guillemots
      Uria aalge on the Isle of May, Scotland. Recruitment of a total of 2757
      individually marked guillemots over 17 years was modelled as a process where
      individuals had to move from an unobservable state at sea, through a nonbreeding
      state present in the colony, to the breeding state. The probabilities of
      individuals returning to the colony in a given year, at age 2 and 3-4 years, were
      positively correlated with an environmental covariate, the winter North Atlantic
      Oscillation index (WNAO) in the previous years. 2. For 2 year olds, there was a
      negative relationship with breeding population size, suggesting that density
      dependence operated in this colony through limitation of food or some other
      resource. 3. Survival over the first 2 years of life varied with cohort, but was
      unrelated to the WNAO. Mean survival over this 2-year period was high at 0.576
      (95% CI: 0.444; 0.708). 4. This high survival, combined with a low 'local'
      survival after age 5 years of 0.695 (0-654; 0.733) and observations of Isle of
      May chicks at other colonies, suggests that most surviving chicks return to the
      natal colony before deciding whether to recruit there or move elsewhere.

PMID- 16903061
TI  - Species loss and secondary extinctions in simple and complex model communities.
AB  - 1. The loss of a species from an ecological community can trigger a cascade of
      secondary extinctions. Here we investigate how the complexity (connectance) of
      model communities affects their response to species loss. Using dynamic analysis
      based on a global criterion of persistence (permanence) and topological analysis
      we investigate the extent of secondary extinctions following the loss of
      different kinds of species. 2. We show that complex communities are, on average,
      more resistant to species loss than simple communities: the number of secondary
      extinctions decreases with increasing connectance. However, complex communities
      are more vulnerable to loss of top predators than simple communities. 3. The loss
      of highly connected species (species with many links to other species) and
      species at low trophic levels triggers, on average, the largest number of
      secondary extinctions. The effect of the connectivity of a species is strongest
      in webs with low connectance. 4. Most secondary extinctions are due to direct
      bottom-up effects: consumers go extinct when their resources are lost. Secondary
      extinctions due to trophic cascades and disruption of predator-mediated
      coexistence also occur. Secondary extinctions due to disruption of predator
      mediated coexistence are more common in complex communities than in simple
      communities, while bottom-up and top-down extinction cascades are more common in
      simple communities. 5. Topological analysis of the response of communities to
      species loss always predicts a lower number of secondary extinctions than dynamic
      analysis, especially in food webs with high connectance.

PMID- 16903062
TI  - Changing habitat associations of a thermally constrained species, the silver
      spotted skipper butterfly, in response to climate warming.
AB  - 1. The impact of climate change on the distribution, abundance, phenology and
      ecophysiology of species is already well documented, whereas the influence of
      climate change on habitat choice and utilization has received little attention.
      Here we report the changing habitat associations of a thermally constrained
      grassland butterfly, Hesperia comma, over 20 years. 2. Between 1982 and 2001-2,
      the optimum percentage of bare ground within habitat used for egg-laying shifted
      from 41% to 21%. 3. Egg-laying rates are temperature-dependent and females
      actively adjust microhabitat usage in response to temperature variations;
      relatively warmer host plants are chosen or oviposition at low ambient
      temperatures, and cooler host plants at high ambient temperatures. 4. Climate
      warming has increased the availability of thermally suitable habitat for H. comma
      at the cool, northern edge of the species' distribution, therefore increasing:
      (a) egg-laying rate and potentially the realized rate of population increase; (b)
      effective area of habitat patches as more microhabitats within a given vegetation
      fragment are now suitable for egg-laying; (c) buffering of populations against
      environmental variation as eggs are laid within a wider range of microhabitats;
      and (d) the number of habitat patches in the landscape that are currently
      available for colonization (including the use of more northerly facing aspects;
      Thomas et al., Nature, 2001, 411, 577-581). 5. Conservationists often assume the
      habitat requirements of a species to be constant, and manage habitats to maintain
      these conditions. For many species, these requirements are likely to change in
      response to climate warming, and care must be taken not to manage habitats based
      on outdated prescriptions.

PMID- 16903063
TI  - Ecological constraints on breeding system evolution: the influence of habitat on
      brood desertion in Kentish plover.
AB  - 1. One of the fundamental insights of behavioural ecology is that resources
      influence breeding systems. For instance, when food resources are plenty, one
      parent is able to care for the young on its own, so that the other parent can
      desert and became polygamous. We investigated this hypothesis in the context of
      classical polyandry when females may have several mates within a single breeding
      season, and parental duties are carried out largely by the male. 2. We studied a
      precocial wader, the Kentish plover Charadrius alexandrinus, that exhibits
      variable brood care such that the chicks may be raised by both parents, only by
      the female or, more often, only by the male. The timing of female desertion
      varies: some females desert their brood at hatching of the eggs and lay a clutch
      for a new mate, whereas other females stay with their brood until the chicks
      fledge. Kentish plovers are excellent organisms with which to study breeding
      system evolution, as some of their close relatives exhibit classical polyandry
      (Eurasian dotterel Eudromias morinellus, mountain plover Charadrius montanus),
      whereas others are polygynous (northern lapwing Vanellus vanellus). 3. Kentish
      plovers raised their broods in two habitats in our study site in southern Turkey:
      saltmarsh and lakeshore. Food intake was higher on the lakeshore than in the
      saltmarsh as judged from feeding behaviour of chicks and adults. As the season
      proceeded and the saltmarsh dried out, the broods moved toward the lakeshore. 4.
      As the density of plovers increased on lakeshore, the parents spent more time
      defending their young, and female parents stayed with their brood longer on the
      lakeshore. 5. We conclude that the influence of food abundance on breeding
      systems is more complex than currently anticipated. Abundant food resources
      appear to have profound implications on spatial distribution of broods, and the
      social interactions between broods constrain female desertion and polyandry.

PMID- 16903064
TI  - Spatial aggregation and association in different resource-patch distributions:
      experimental analysis with Drosophila.
AB  - 1. Laboratory experiments using homogeneous resources were conducted to examine
      intra- and interspecific spatial egg distribution of D. simulans, D. auraria and
      D. immigrans in three different resource-patch distribution patterns: patchy,
      even and clustered. 2. Individuals of each species were introduced separately or
      simultaneously into the cage, into which artificial substrates were placed and
      allowed to oviposit for 24 h. Spatial analyses were performed with indices of
      intraspecific aggregation (J), interspecific association (C) and L-function based
      on Ripley's K-function. 3. Eggs were always spatially aggregated irrespective of
      species and the resource-patch distribution patterns. Spatial egg aggregation was
      influenced significantly by the resource-patch distribution pattern and tended to
      be weaker in the clustered resource-patch distribution than in the patchy or even
      resource-patch distribution. 4. Spatial extent of egg aggregation was always
      beyond the single resource patch scale, indicating aggregation of ovipositing
      females. 5. Interspecific association of egg distribution was absent or very
      weak. Thus, these results present experimental evidence of independent egg
      aggregation among drosophilids.

PMID- 16903066
TI  - Nutritional value of cannibalism and the role of starvation and nutrient
      imbalance for cannibalistic tendencies in a generalist predator.
AB  - 1. Cannibalism is considered an adaptive foraging strategy for animals of various
      trophic positions, including carnivores. However, previous studies on wolf
      spiders have questioned the high nutritional value of cannibalism. We therefore
      analysed two different aspects of nutritional quality of conspecifics in the wolf
      spider Pardosaprativaga: their value for survival, growth and development; and
      the growth efficiency of feeding on conspecifics. We also measured the propensity
      for cannibalistic attacks and the consumption rate of conspecifics in an
      experiment where hunger level and nutrient balance were manipulated. In all
      experiments, cannibalism was compared with predation on fruit flies as control
      prey. 2. The growth experiment gave ambiguous results regarding the nutritional
      quality of conspecifics. Spiders on pure cannibalistic diets split into two
      distinct groups, one performing much better and the other much worse than spiders
      on fruit fly diets. We discuss the possibility that the population is dimorphic
      in its cannibalistic propensity, with the latter group of individuals showing a
      high level of inhibition against cannibalistic attacks in spite of a high
      nutritional value of cannibalism. 3. The food utilization experiment confirmed
      the high nutritional quality of conspecifics, as cannibalistic spiders had the
      same growth rate as spiders fed insect prey in spite of a much lower consumption
      rate. 4. Inhibition against cannibalistic attacks was demonstrated in medium
      sized juveniles: only half of the spiders attacked a prescribed victim of 50% the
      size of their opponents, and the latency for those that did attack was more than
      half an hour, compared with a few minutes for spiders fed fruit flies. 5.
      Nutrient-imbalanced spiders utilized an alternative insect diet less efficiently
      than balanced spiders, whereas no difference was present in efficiency of
      utilizing conspecifics. This result indicates that spiders can remedy at least
      part of a nutrient imbalance through cannibalism. 6. As spiders can escape
      nutritional imbalance as well as restore energy reserves through cannibalism, we
      predicted both nutrient imbalance and hunger to stimulate cannibalism. This
      prediction was confirmed only with respect to hunger. Nutrient-imbalanced spiders
      had reduced cannibalistic consumption, perhaps due to lowered predatory
      aggressiveness as a result of bad condition.

PMID- 16903065
TI  - Evaluating the performance of species richness estimators: sensitivity to sample
      grain size.
AB  - 1. Fifteen species richness estimators (three asymptotic based on species
      accumulation curves, 11 nonparametric, and one based in the species-area
      relationship) were compared by examining their performance in estimating the
      total species richness of epigean arthropods in the Azorean Laurisilva forests.
      Data obtained with standardized sampling of 78 transects in natural forest
      remnants of five islands were aggregated in seven different grains (i.e. ways of
      defining a single sample): islands, natural areas, transects, pairs of traps,
      traps, database records and individuals to assess the effect of using different
      sampling units on species richness estimations. 2. Estimated species richness
      scores depended both on the estimator considered and on the grain size used to
      aggregate data. However, several estimators (ACE, Chao 1, Jackknifel and 2 and
      Bootstrap) were precise in spite of grain variations. Weibull and several recent
      estimators [proposed by Rosenzweig et al. (Conservation Biology, 2003, 17, 864
      874), and Ugland et al. (Journal of Animal Ecology, 2003, 72, 888-897)] performed
      poorly. 3. Estimations developed using the smaller grain sizes (pair of traps,
      traps, records and individuals) presented similar scores in a number of
      estimators (the above-mentioned plus ICE, Chao2, Michaelis-Menten, Negative
      Exponential and Clench). The estimations from those four sample sizes were also
      highly correlated. 4. Contrary to other studies, we conclude that most species
      richness estimators may be useful in biodiversity studies. Owing to their
      inherent formulas, several nonparametric and asymptotic estimators present
      insensitivity to differences in the way the samples are aggregated. Thus, they
      could be used to compare species richness scores obtained from different sampling
      strategies. Our results also point out that species richness estimations coming
      from small grain sizes can be directly compared and other estimators could give
      more precise results in those cases. We propose a decision framework based on our
      results and on the literature to assess which estimator should be used to compare
      species richness scores of different sites, depending on the grain size of the
      original data, and of the kind of data available (species occurrence or abundance
      data).

PMID- 16903067
TI  - Animal movement rates as behavioural bouts.
AB  - Johnson et al. (Journal of Animal Ecology, 2002, 71, 225-235) have proposed a new
      technique for identifying scales of movement in animals. Animals are located at
      certain time intervals, and movement rates between successive animal relocations
      are calculated. The null model of a nonscalar response predicts a decreasing
      linear relationship between log (frequency) vs. movement rate, while a scalar
      response predicts a monotonically decreasing curve with an inflection point at
      the separation between the processes. I tested this technique using three types
      of simulated movement paths: correlated random walks, directed walks, and
      movements in patchy habitat. None of the simulations showed the results expected
      by the technique. This occurs because the technique assumes that movement rates
      are exponentially distributed, which is highly unlikely. Thus before this
      technique can be applied to animal movement data we need to understand how
      spatial and temporal scale, as well as sampling interval, affect the frequency
      histogram of animal movement rates.

PMID- 16903069
TI  - The senator from Starbucks.

PMID- 16903070
TI  - The green machine.

PMID- 16903071
TI  - Antibacterial, antifungal and anticonvulsant evaluation of novel newly
      synthesized 1-[2-(1H-tetrazol-5-yl)ethyl]-1H-benzo[d][1, 2,3]triazoles.
AB  - Several novel 1-[2-(1H-tetrazol-5-yl) ethyl]-1H-benzo[d][1,2,3]triazoles (3a-h)
      have been synthesized by the condensation of 1-[2-(1H-tetrazol-5-yl)-ethyl]-1H
      benzotriazole (2) and appropriate acid chlorides. 1-[2-(1H-tetrazol-5-yl)-ethyl]
      1H-benzotriazole (2) was synthesized by reacting 3-(1H-benzo[d][1,2,3]triazol-1
      yl)propanenitrile with sodium azide and ammonium chloride in the presence of
      dimethylformamide. The synthesized compounds were characterized by IR and PMR
      analysis. The titled compounds were evaluated for their in-vitro antibacterial
      and antifungal activity by the cup plate method and anticonvulsant activity
      evaluated by the maximal electroshock induced convulsion method in mice. All
      synthesized compounds exhibited moderate antibacterial activity against Bacillus
      subtilis and moderate antifungal activity against Candida albicans. Compounds 5
      (2-(1H-benzo[d][1,2,3]triazo-1-yl)ethyl)-1H-tetrazol-1-yl)(4
      aminophenyl)methanone 3d and 5-(2-(1 H-benzo[d][1,2,3]triazo-1-yl)ethyl)-1H
      tetrazol-1-yl)(2-aminophenyl)methanone 3e elicited excellent anticonvulsant
      activity.

PMID- 16903072
TI  - Cytotoxicity and DNA topoisomerase inhibitory activity of constituents isolated
      from the fruits of Evodia officinalis.
AB  - Four alkaloids (1-4), three quinolone alkaloids (5-7), and three flavanoid
      glucosides (8-10) were isolated from the fruits of Evodia officinalis Dode, and
      their structures were determined from chemical and spectral data. Compounds, 3,
      8, 9 and 10 were isolated from this plant for the first time. Of these compounds,
      1-3 and 5-7 exhibited moderate cytotoxicities against cultured human colon
      carcinoma (HT-29), human breast carcinoma (MCF-7), and human hepatoblastoma (HepG
      2). Compound 8 showed strong inhibitory effects on DNA topoisomerases I and II
      (70 and 96% inhibition at a concentration of 20 microM, respectively).

PMID- 16903073
TI  - Cytotoxic and COX-2 inhibitory constituents from the aerial parts of Aralia
      cordata.
AB  - Three diterpenes (1, 8, and 9), three triterpenes (3, 4, and 7), one saponin
      (11), four sterols (2, 5, 6, and 12), and one cerebroside (10) were isolated from
      the EtOH extract of the aerial parts of Aralia cordata by repeated silica gel
      column chromatography. Their chemical structures were identified by comparing
      their physicochemical and spectral data with those published in literatures. All
      isolated compounds were evaluated for their cytotoxicity against L1210, K562, and
      LLC tumor cell lines using MTT assay. Of which, 3beta,5alpha-dihydroxy-6beta
      methoxyergosta-7,22-diene (6) showed a potent cytotoxicity against all cell lines
      with IC50 values of 11.7, 11.9, and 15.1 microM, respectively, while compounds 1,
      5, and 11 showed a moderate or weak cytotoxicity. These isolates were also
      examined for their inhibitory activity against COX-1 and COX-2. Although most
      compounds, except for 2, 10, and 12, showed a strong inhibitory activity against
      COX-1, they exhibited a moderate or weak inhibitory activity against COX-2.

PMID- 16903074
TI  - Structure-activity relationship study of asiatic acid derivatives for new wound
      healing agent.
AB  - Ten semi-synthetic derivatives of asiatic acid were prepared and their wound
      healing effects were evaluated by employing a tensile strength assay and a wound
      area assay. Among them, ethoxymethyl 2-oxo-3,23-isopropylidene-asiatate (12)
      showed the strongest and the fastest wound healing activity. Furthermore, it left
      the smallest scar after healing.

PMID- 16903075
TI  - A convenient synthesis of an anti-Helicobacter pylori agent, dehydrodiconiferyl
      alcohol.
AB  - Potential anti-Helicobacter pylori agent dehydrodiconiferyl alcohol was
      synthesized in 44% overall yield, starting from vanillin which could be
      commercially available. Carbon extension of vanillin followed by the Horner
      Wadsworth-Emmons reaction, a biomolecular radical coupling reaction and DIBAL-H
      reduction gave dehydrodiconiferyl alcohol.

PMID- 16903076
TI  - Influence of ginsenoside Rb1 on brain neurosteroid during acute immobilization
      stress.
AB  - This study examined whether or not acute stress is linked to increases in the
      neurosteroid levels, which is a well-known neurotransmitters associated with
      stress stimuli. The ginsenoside, Rb1, was tested in order to better understand
      its potential effects on altering the neurosteroid levels and ultimately
      attenuating stress. The optimal stressed condition was checked by measuring the
      5a-dihydroprogesterone (DHP) and allopregnanolone (THP) levels in the brain after
      immobilization stress at various times. Based on this result, an acute stress
      model was set up to give 30 min of immobilization stress. The DHP and THP brain
      levels of the stressed mice were then investigated after administering Rb1 orally
      (10 mg/kg). These results were compared with the neurosteroid level in the
      stressed mice not given Rbl. Saline was administered orally to the nonstressed
      mice to check the placebo effect. Acute immobilization stress induced an increase
      in the THP and DHP concentration in the frontal cortex and cerebellum. When Rb1
      was administered orally prior to immobilization stress, the THP level in the
      frontal cortex and cerebellum was significantly lower than that in the stressed
      animals not given Rbl. On the other hand, the DHP level was lower in the
      cerebellum only. This suggests that the metabolism of the brain neurosteroids is
      linked to psychological stress, and Rb1 attenuates the stress-induced increase in
      neurosteroids.

PMID- 16903077
TI  - Effect of biochanin A on the aryl hydrocarbon receptor and cytochrome P450 1A1 in
      MCF-7 human breast carcinoma cells.
AB  - Phytoestrogen biochanin A is an isoflavone derivative isolated from red clover
      Trifolium pratense with anticarcinogenic properties. This study examined the
      action of biochanin A with the carcinogen activation pathway that is mediated by
      the aryl hydrocarbon receptor (AhR) in MCF-7 breast carcinoma cells. Treating the
      cells with biochanin A alone caused the accumulation of CYP1A1 mRNA and an
      increase in CYP1A1-specific 7-ethoxyresorufin O-deethylase (EROD) activity in a
      dose dependent manner. A concomitant treatment with 7,12
      dimethylbenz[a]anthracene (DMBA) and biochanin A markedly reduced the DMBA
      inducible EROD activity and CYP1A1 mRNA level. In addition, the biochanin A
      treatment alone activated the DNA-binding capacity of the AhR for the dioxin
      response element (DRE) of CYP1A1, as measured by the electrophoretic-mobility
      shift assay (EMSA). EMSA revealed that biochanin A reduced the level of the DMBA
      inducible AhR-DRE binding complex. Furthermore, biochanin A competed with the
      prototypical AhR ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), for binding
      to the AhR in an isolated rat cytosol. The biochanin A competitively inhibited
      the metabolic activation of DMBA, as measured by the formation of the DMBA-DNA
      adducts. These results suggest that biochanin A may thus be a natural ligand to
      bind on AhR. Therefore, biochanin A may be due to act an antagonist/agonist of
      the AhR pathway.

PMID- 16903078
TI  - Glycation-induced inactivation of antioxidant enzymes and modulation of cellular
      redox status in lens cells.
AB  - Oxidative mechanisms are thought to have a major role in cataract formation and
      diabetic complications. Antioxidant enzymes play an essential role in the
      antioxidant system of the cells that work to maintain low steady-state
      concentrations of the reactive oxygen species. When HLE-B3 cells, a human lens
      cell line were exposed to 50-100 mM glucose for 3 days, decrease of viability,
      inactivation of antioxidant enzymes, and modulation of cellular redox status were
      observed. Significant increase of cellular oxidative damage reflected by lipid
      peroxidation and DNA damage were also found. The glycation-mediated inactivation
      of antioxidant enzymes may result in the perturbation of cellular antioxidant
      defense mechanisms and subsequently lead to a pro-oxidant condition and may
      contribute to various pathologies associated with the long term complications of
      diabetes.

PMID- 16903079
TI  - Relationships between the larval growth inhibition of Caenorhabditis elegans by
      apigenin derivatives and their structures.
AB  - Due to consumer reluctance to take synthetic drugs for nematode infections and
      the appearance of resistance to anthelminthic drugs, new drugs from natural
      products must be developed. Caenorhabditis elegans is one of the freely living
      nematodes and serves as a good model system for screening anthelminthic drugs. In
      this study, thirteen flavonoid derivatives were tested for anthelminthic activity
      and the relationships between their activities and structures were investigated.
      The structural information combined with the data for the larval growth
      inhibition of C. elegans provided meaningful structural insights in the search
      for new anthelminthic drugs.

PMID- 16903080
TI  - Naphthopyrone glucosides from the seeds of Cassia tora with inhibitory activity
      on advanced glycation end products (AGEs) formation.
AB  - Three naphthopyrone glucosides, cassiaside (1), rubrofusarin-6-O-beta-D
      gentiobioside (2), and toralactone-9-O-beta-D-gentiobioside (3), were isolated
      from the BuOH-soluble extract of the seeds of Cassia tora as active constituents,
      using an in vitro bioassay based on the inhibition of advanced glycation end
      products (AGEs) to monitor chromatographic fractionation. The structures of 1-3
      were determined by spectroscopic data interpretation, particularly by extensive
      1D and 2D NMR studies. All the isolates (1-3) were evaluated for the inhibitory
      activity on AGEs formation in vitro.

PMID- 16903081
TI  - Artemisolide from Artemisia asiatica: nuclear factor-kappaB (NF-kappaB) inhibitor
      suppressing prostaglandin E2 and nitric oxide production in macrophages.
AB  - Aerial parts of Artemisia asiatica (Compositae) have been traditionally used as
      an oriental medicine for the treatment of inflammatory and ulcerogenic diseases.
      In the present study, artemisolide was isolated as a nuclear factor (NF)-kappaB
      inhibitor from A. asiatica by activity-guided fractionation. Artemisolide
      inhibited NF-kappaB transcriptional activity in lipopolysaccharide (LPS)
      stimulated macrophages RAW 264.7 with an IC50 value of 5.8 microM. The compound
      was also effective in blocking NF-kappaB transcriptional activities elicited by
      the expression vector encoding the NF-kappaB p65 or p50 subunits bypassing the
      inhibitory kB degradation signaling NF-kappaB activation. The macrophages
      markedly increased their PGE2 and NO production upon exposure to LPS alone.
      Artemisolide inhibited LPS-induced PGE2 and NO production with IC50 values of 8.7
      microM and 6.4 microM, respectively, but also suppressed LPS-induced synthesis of
      cyclooxygenase (COX)-2 or inducible NO synthase (iNOS). Taken together,
      artemisolide is a NF-kappaB inhibitor that attenuates LPS-induced production of
      PGE2 or NO via down-regulation of COX-2 or iNOS expression in macrophages RAW
      264.7. Therefore, artemisolide could represent and provide the anti-inflammatory
      principle associated with the traditional medicine, A. asiatica.

PMID- 16903082
TI  - Drug targeting to lungs by way of microspheres.
AB  - In many conventional drug delivery systems in vogue, failure to deliver efficient
      drug delivery at the target site/organs; is evident as a result, less efficacious
      pharmacological response is elicited. Microspheres can be derived a remedial
      measure which can improve site-specific drug delivery to a considerable extent.
      As an application, Lung-targeting Ofloxacin-loaded gelatin microspheres (GLOME)
      were prepared by water in oil emulsion method. The Central Composite Design (CCD)
      was used to optimize the process of preparation, the appearance and size
      distribution were examined by scanning electron microscopy, the aspects such as
      in vitro release characteristics, stability, drug loading, loading efficiency,
      pharmacokinetics and tissue distribution in albino mice were studied. The
      experimental results showed that the microspheres in the range of 0.32-22 microm.
      The drug loading and loading efficiency were 61.05 and 91.55% respectively. The
      in vitro release profile of the microspheres matched the korsmeyer's peppas
      release pattern, and release at 1h was 42%, while for the original drug,
      ofloxacin under the same conditions 90.02% released in the first half an hour.
      After i.v. administration (15 min), the drug concentration of microspheres group
      in lung in albino mice was 1048 microg/g, while that of controlled group was 6.77
      microg/g. GLOME found to release the drug to a maximum extent in the target
      tissue, lungs.

PMID- 16903083
TI  - The transport of organic cations in the small intestine: current knowledge and
      emerging concepts.
AB  - A wide variety of drugs and endogenous bioactive amines are organic cations
      (OCs). Approximately 40% of all conventional drugs on the market are OCs. Thus,
      the transport of xenobiotics or endogenous OCs in the body has been a subject of
      considerable interest, since the discovery and cloning of a family of OC
      transporters, referred to as organic cation transporter (OCTs), and a new
      subfamily of OCTs, OCTNs, leading to the functional characterization of these
      transporters in various systems including oocytes and some cell lines. Organic
      cation transporters are critical in drug absorption, targeting, and disposition
      of a drug. In this review, the recent advances in the characterization of organic
      cation transporters and their distribution in the small intestine are discussed.
      The results of the in vitro transport studies of various OCs in the small
      intestine using techniques such as isolated brush-border membrane vesicles,
      Ussing chamber systems and Caco-2 cells are discussed, and in vivo knock-out
      animal studies are summarized. Such information is essential for predicting
      pharmacokinetics and pharmacodynamics and in the design and development of new
      cationic drugs. An understanding of the mechanisms that control the intestinal
      transport of OCs will clearly aid achieving desirable clinical outcomes.

PMID- 16903084
TI  - Biodiversity in agricultural landscapes: saving natural capital without losing
      interest.

PMID- 16903085
TI  - Framing sustainability.

PMID- 16903086
TI  - The culture of growth and the culture of limits.

PMID- 16903087
TI  - For whom the roll calls.

PMID- 16903088
TI  - Special section: the Northwest Forest Plan: a global model of forest management
      in contentious times.

PMID- 16903089
TI  - The Northwest Forest Plan: origins, components, implementation experience, and
      suggestions for change.
AB  - In the 1990s the federal forests in the Pacific Northwest underwent the largest
      shift in management focus since their creation, from providing a sustained yield
      of timber to conserving biodiversity, with an emphasis on endangered species.
      Triggered by a legal challenge to the federal protection strategy for the
      Northern Spotted Owl (Strix occidentalis caurina), this shift was facilitated by
      a sequence of science assessments that culminated in the development of the
      Northwest Forest Plan. The plan, adopted in 1994, called for an extensive system
      of late-successional and riparian reserves along with some timber harvest on the
      intervening lands under a set of controls and safeguards. It has proven more
      successful in stopping actions harmful to conservation of old-growth forests and
      aquatic systems than in achieving restoration goals and economic and social
      goals. We make three suggestions that will allow the plan to achieve its goals:
      (1) recognize that the Northwest Forest Plan has evolved into an integrative
      conservation strategy, (2) conserve old-growth trees and forests wherever they
      occur and (3) manage federal forests as dynamic ecosystems.

PMID- 16903090
TI  - Conservation of the northern spotted owl under the Northwest Forest Plan.
AB  - Development of the Northwest Forest Plan (NWFP) was motivated by concerns about
      the over-harvest of late-seral forests and the effects of intensive forest
      management on the long-term viability of the Northern Spotted Owl (Strix
      occidentalis caurina). Following several years of intense political and legal
      debates, the final NWFP was approved in 1994. Even though the plan evolved with a
      broad ecosystem perspective, it remained anchored in the Spotted Owl reserve
      design proposed in 1990. Based on a criterion of stable or increasing
      populations, a decade later it remains unclear whether the enactment of the NWFP
      has improved the conservation status of Spotted Owls. The results of intensive
      monitoring of several Spotted Owl populations for over a decade suggest a
      continuing range-wide decline even though rates of timber harvest have declined
      dramatically on federal lands. The cause of the decline is difficult to determine
      because the research needed to establish cause and effect relations has not been
      done. One plausible hypothesis is that the owl's life history greatly constrains
      its rate of population growth even when habitat is no longer limiting. Since
      enactment of the NWFP, new threats have arisen, including the movement of Barred
      Owls (S. varia) into the range of the Spotted Owl, political pressure to increase
      levels of timber harvest, and recent changes to forest laws that eliminate the
      requirement to assess the viability of wildlife populations on U.S. Department of
      Agriculture Forest Service lands. At this time is appears that Spotted Owl
      conservation rests critically on continued implementation of the protections
      afforded by the NWFP and the U.S. Endangered Species Act.

PMID- 16903091
TI  - Conservation of the marbled murrelet under the Northwest Forest Plan.
AB  - The Marbled Murrelet (Brachyramphus marmoratus) was listed as threatened in 1992,
      primarily because of loss of its old-forest nesting habitat. Monitoring conducted
      over the first 10 years following implementation of the Northwest Forest Plan
      shows at-sea murrelet populations appear to be stationary, but recruitment is
      very low and demographic models project a 4-6% annual rate of decline. Monitoring
      of nesting habitat indicated there were about 1.6 million ha of higher
      suitability nesting habitat on all lands at the start of the plan, about half of
      which occurred on federal lands. Most (88%) of higher-suitability habitat on
      federal lands was protected within reserves. Over the past 10 years, losses of
      habitat due primarily to fire have totaled about 2% on federal lands. Losses have
      been much greater (12%) on nonfederal lands, due primarily to timber harvest.
      Habitat is expected to accrue within reserves as younger forest matures and
      attains sufficient diameter to support nesting sites. At-sea estimates of
      population size are strongly and positively correlated with amounts of adjacent
      nesting habitat at a broad scale, supporting the idea that amounts of nesting
      habitat are a primary driver in wide-scale murrelet population distribution.
      Conditions at sea, however such as temperature regimes, prey availability, and
      pollutants, continue to affect murrelet populations. The system of large reserves
      seems to have achieved the short-term objective of conserving much of the
      remaining nesting habitat on federal lands. These reserves are also likely to
      contribute to the long-term objective of creating large, contiguous blocks of
      nesting habitat. The plan has a primary role in conserving and restoring nesting
      habitat on federal land but will succeed in this role only if land allocations
      calling for such protection are in place for many decades.

PMID- 16903093
TI  - The Aquatic Conservation Strategy of the Northwest Forest Plan.
AB  - Implemented in 1994, the Aquatic Conservation Strategy of the Northwest Forest
      Plan was designed to restore and maintain ecological processes for aquatic and
      riparian area conservation on federal lands in the western portion of the Pacific
      Northwest. We used decision support models to quantitatively evaluate changes in
      the condition of selected watersheds. In the approximately 10 years since
      strategy implementation, watershed condition scores changed modestly, but
      conditions improved in 64% of 250 sampled watersheds, declined in 28%, and
      remained relatively the same in 7%. Watersheds that had the largest declines
      included some where wildfires burned 30-60% of their area. The overall
      statistical distribution of the condition scores did not change significantly,
      however Much of the increase in watershed condition was related to improved
      riparian conditions. The number of large trees (>51 cm diameter at breast height)
      increased 2-4%, and there were substantial reductions in tree harvest and other
      disturbances along streams. Whether such changes will translate into longer-term
      improvements in aquatic ecosystems across broader landscapes remains to be seen.

PMID- 16903092
TI  - Protecting rare, old-growth, forest-associated species under the Survey and
      Manage Program guidelines of the Northwest Forest Plan.
AB  - The Survey and Manage Program of the Northwest Forest Plan (NWFP) represents an
      unparalleled attempt to protect rare, little-known species associated with late
      successional and old-growth forests on more than 9.7 million ha of federal lands.
      Approximately 400 species of amphibians, bryophytes, fungi, lichens, mollusks,
      vascular plants, arthropod functional groups, and one mammal were listed under
      this program because viability evaluations indicated the plan's network of
      reserve land allocations might not sustain the species over time. The program's
      standards and guidelines used an adaptive approach, protecting known sites and
      collecting new information to address concerns for species persistence and to
      develop management strategies. Since implementation in 1994, approximately 68,000
      known sites have been recorded at an expense of several tens of millions of
      dollars. New knowledge from surveys reduced concern for nearly 100 species, and
      they were removed from the protection list. Although successful in protecting
      hundreds of rare species not typically considered in most conservation programs,
      some of the enacted conservation measures created conflicts in meeting other
      management objectives of the plan, particularly timber harvest. The program
      accrued important gains in knowledge, reduced uncertainty about conservation of a
      number of species, and developed new methods of species inventory that will be
      useful in future management planning and implementation at many scales. The
      program, however was not completed because of changes in land-management
      philosophy. Ongoing litigation regarding its termination and potential changes to
      the plan cast further uncertainty on how the original goal of maintaining
      persistence of late-successional and old-growth species will be met and measured.
      The outcomes, controversies, and management frustrations of the program exemplify
      the inherent difficulties in balancing broad, regional conservation goals with
      social and economic goals of the NWFP Defining acceptable trade-offs to reach
      that balance and developing practical conservation solutions remain challenges
      for the science and management communities. Lessons learned from the program
      provide a valuable biological and managerial reference to benefit future
      discussion on meeting those challenges.

PMID- 16903094
TI  - The Northwest Forest Plan as a model for broad-scale ecosystem management: a
      social perspective.
AB  - I evaluated the Northwest Forest Plan as a model for ecosystem management to
      achieve social and economic goals in communities located around federal forests
      in the US. Pacific Northwest. My assessment is based on the results of
      socioeconomic monitoring conducted to evaluate progress in achieving the plan's
      goals during its first 10 years. The assessment criteria I used related to
      economic development and social justice. The Northwest Forest Plan incorporated
      economic development and social justice goals in its design. Socioeconomic
      monitoring results indicate that plan implementation to achieve those goals met
      with mixed success, however I hypothesize there are two important reasons the
      plan's socioeconomic goals were not fully met: some of the key assumptions
      underlying the implementation strategies were flawed and agency institutional
      capacity to achieve the goals was limited. To improve broad-scale ecosystem
      management in the future, decision makers should ensure that natural-resource
      management policies are socially acceptable; land-management agencies have the
      institutional capacity to achieve their management goals; and social and economic
      management goals (and the strategies for implementing them) are based on accurate
      assumptions about the relations between the resources being managed and well
      being in local communities. One of the difficulties of incorporating economic
      development and social justice goals in conservation initiatives is finding ways
      to link conservation behavior and development activities. From a social
      perspective, the Northwest Forest Plan as a model for ecosystem management is
      perhaps most valuable in its attempt to link the biophysical and socioeconomic
      goals of forest management by creating high-quality jobs for residents of forest
      communities in forest stewardship and ecosystem management work, thereby
      contributing to conservation.

PMID- 16903095
TI  - Public timber supply, market adjustments, and local economies: economic
      assumptions of the Northwest Forest Plan.
AB  - The Northwest Forest Plan in the Pacific Northwest sought to stabilize local
      economies, including local employment and income, by stabilizing the flow of wood
      fiber from public forests. This is also a common forest management objective in
      other regions and countries. Because this economic strategy ignores basic market
      adjustments, it is likely to fail and to unnecessarily damage forest ecosystems.
      Application of basic economic principles on how markets operate significantly
      changes the apparent efficacy of efforts to manage local economies by managing
      timber supply. The emphasis on timber supply tends to ignore the dominant role
      that the demand for wood fiber and wood products, rather than wood-fiber supply,
      plays in determining levels of harvest and production. Contemporary economics
      indicates that markets tend to operate to offset reductions in wood-fiber supply.
      This significantly moderates the economic cost of reducing commercial timber
      harvest in the pursuit of environmental objectives. In addition, contemporary
      economic analysis indicates that the economic links between natural forests and
      local communities are much broader than simply the flow of commercially valuable
      logs to manufacturing facilities. At least in the United States, the flow of
      environmental services from natural forests has increasingly become an amenity
      that has drawn people and economic activity to forested areas. Attractive site
      specific qualities, including those supported by natural forests, can potentially
      support local economic development even in the face of reduced timber harvests.
      These market-related adjustments partially explain the Northwest Forest Plan's
      overestimation of the expected regional impacts associated with reduced federal
      timber supply and the ineffectiveness of the plan's efforts to protect
      communities by stabilizing federal timber supply

PMID- 16903096
TI  - Conserving old-growth forest diversity in disturbance-prone landscapes.
AB  - A decade after its creation, the Northwest Forest Plan is contributing to the
      conservation of old-growth forests on federal land. However the success and
      outlook for the plan are questionable in the dry provinces, where losses of old
      growth to wildfire have been relatively high and risks of further loss remain. We
      summarize the state of knowledge of old-growth forests in the plan area, identify
      challenges to conserve them, and suggest some conservation approaches that might
      better meet the goals of the plan. Historically, old-growth forests in these
      provinces ranged from open, patchy stands, maintained by frequent low-severity
      fire, to a mosaic of dense and open stands maintained by mixed-severity fires.
      Old-growth structure and composition were spatially heterogeneous, varied
      strongly with topography and elevation, and were shaped by a complex disturbance
      regime of fire, insects, and disease. With fire suppression and cutting of large
      pines (Pinus spp.) and Douglas-firs (Pseudotsuga menziesii [Mirbel] Franco), old
      growth diversity has declined and dense understories have developed across large
      areas. Challenges to conserving these forests include a lack of definitions
      needed for planning of fire-dependent old-growth stands and landscapes, and
      conflicts in conservation goals that can be resolved only at the landscape level.
      Fire suppression has increased the area of the dense, older forest favored by
      Northern Spotted Owls (Strix occidentalis caurina) but increased the probability
      of high-severity fire. The plan allows for fuel reduction in late-successional
      reserves; fuel treatments, however apparently have not happened at a high enough
      rate or been applied in a landscape-level approach. Landscape-level strategies
      are needed that prioritize fuel treatments by vegetation zones, develop shaded
      fuel breaks in strategic positions, and thin and apply prescribed fire to reduce
      ladder fuels around remaining old trees. Evaluations of the current and
      alternative strategies are needed to determine whether the current reserve-matrix
      approach is the best strategy to meet plan goals in these dynamic landscapes.

PMID- 16903097
TI  - Status of mature and old-growth forests in the Pacific Northwest.
AB  - Nearly 10 million ha of federal lands in the Pacific Northwest have been managed
      under the Northwest Forest Plan since 1994. The plan reduced logging levels by
      80%; only recently, however have inventories on status and condition of mature
      and old-growth forests become available. Our objectives were to (1) determine the
      areal extent of old (> 150 years) and mature (50-150 years) conifer forests based
      on 2000 Landsat 7 ETM+ imagery, (2) examine levels of protection, (3) determine
      the degree of additional protection afforded to old and mature conifer forests if
      late-successional reserves (LSRs) and inventoried roadless areas (IRAs) were
      fully protected, and (4) review management options to achieve greater protection
      of older forests. The historical extent of old-growth forest in the Pacific
      Northwest was roughly two-thirds (16,672,976 ha) of the total land area. Since
      the time of European settlement, approximately 72% of the original old-growth
      conifer forest has been lost, largely through logging and other developments. Of
      the remaining old growth, the Central and Southern Cascades and Klamath-Siskiyou
      account for nearly half Mature conifer area (4,758,596 ha) nearly equaled the
      amount of old conifer More than 78% of the old growth and 50% of mature forest
      were located on public lands. Approximately one-quarter (1,201,622 ha) of the old
      growth conifer (or 7% of the historical old-growth area) was classified as GAP
      status 1 (strictly protected) or GAP status 2 (moderately protected). The total
      area of LSRs was slightly more than 3 million ha, approximately 36% (1,073,299
      ha) of which contained old-growth conifer forest. Combined old and mature conifer
      within LSRs was approximately 59% of the total LSR area. The total amount of IRA
      for the Pacific Northwest was approximately 1,563,370 ha; of this, 526,912 ha
      (34%) was old growth. The combined area of old-growth conifer forest accounted
      for by protected areas (GAP 1 and 2), LSRs, and IRAs was 2,401,780 ha, which
      accounts for 66% of the old-growth conifer forests on public land, 51% of the old
      conifer in the region, and 14% of the amount that occurred historically. Outside
      these land designations, an additional 1,240,271 ha of old growth are on other
      public land and another 1,023,392 ha are on private lands throughout the Pacific
      Northwest. Our results indicate the need to periodically monitor status and
      condition of older forests and strengthen protections of old growth in the
      region.

PMID- 16903098
TI  - Fire management impacts on invasive plants in the western United States.
AB  - Fire management practices affect alien plant invasions in diverse ways. I
      considered the impact of six fire management practices on alien invasions: fire
      suppression, forest fuel reduction, prescription burning in crown-fire
      ecosystems, fuel breaks, targeting of noxious aliens, and postfire
      rehabilitation. Most western United States forests have had fire successfully
      excluded for unnaturally long periods of time, and this appears to have favored
      the exclusion of alien plant species. Forest fuel reduction programs have the
      potential for greatly enhancing forest vulnerability to alien invasions. In part
      this is due to the focus on reestablishing pre-Euro-American fire regimes on a
      landscape that differs from pre-Euro-American landscapes in the abundance of
      aggressive non-native species. We may be forced to choose between restoring
      "natural"fire regimes or altering fire regimes to favor communities of native
      species. Intensive grazing in many western forests may exacerbate the alien
      problem after fire and temporally decoupling grazing and fire restoration may
      reduce the alien threat. Many shrubland ecosystems such as the Intermountain West
      sagebrush steppe or California chaparral have a natural, high-intensity crown
      fire regime that is less amenable to forest restoration tactics. Historical use
      of prescribed fire for type conversion of shrublands to more useful grazing lands
      has played some role in the massive annual grass invasion that threatens these
      shrublands. Fuel breaks pose a special invasive plant risk because they promote
      alien invasion along corridors into wildland areas. Use of prescription burning
      to eliminate noxious aliens has had questionable success, particularly when
      applied to disturbance-dependent annuals, and success is most likely when coupled
      with ecosystem restoration that alters the competitive balance between aliens and
      natives. Artificial seeding of alien species as a form of postfire stabilization
      appears to cause more problems than it solves and may even enhance alien
      invasion.

PMID- 16903099
TI  - The role of roadsides in plant invasions: a demographic approach.
AB  - Non-native plant species are common along roadsides, but presence does not
      necessarily indicate spread along the road axis. Roadsides may serve merely as
      habitat for a species spreading independently of roads. The potential conduit
      function of roads depends on the habitat specificity of the spreading species,
      its dispersal range relative to the spacing of roads in the landscape, and the
      relative importance of long- and short-range dispersal. We describe a demographic
      model of the road x species interaction and suggest methods of assessing conduit
      function in the field based on the model results. A species limited to roadside
      habitat will be constrained to spread along the road axis unless its long-range
      dispersal is sufficient to carry it across the intervening unfavorable area to
      another road. It will propagate along a road corridor at a rate determined by the
      scale of short-range dispersal. Effective management of an invasion requires
      distinguishing between the habitat and conduit functions, a distinction difficult
      to make with only snapshot data. Invasions can be reconstructed by several
      methods, but none is totally satisfactory. We suggest comparing stem
      distributions on transects parallel and perpendicular to the road axis, and
      beside the road, and away from it, with an idealized Gaussian curve. Such
      comparisons would allow discrimination between pattern determined by habitat
      suitability and pattern reflecting random and facilitated dispersal.

PMID- 16903100
TI  - The role of ecolabeling in fisheries management and conservation.
AB  - The Marine Stewardship Council (MSC) regulates the ecolabeling of products from
      fisheries with the aim of promoting sustainable fishery practices. To date 11
      fisheries have attained full certification and a further 7 are under review.
      Together these fisheries offer 220 ecolabeled marine products to consumers.
      Despite great potential to encourage sustainable fisheries, and thereby bring
      conservation benefits to marine systems, a range of issues may limit the wider
      uptake of MSC ecolabeled products. These include a general lack of consumer
      concern for marine fishes and sustainable fisheries, an absence of guaranteed
      continued financial benefits to participating fishers, and difficulties of
      quality assurance that are related to complexities of monitoring compliance of
      marine fisheries. In addition, it is apparent that property rights over the
      fishery seem to be an essential prerequisite for engagement in MSC, and this is
      one major impediment to wider uptake of the scheme in current marine fisheries,
      which tend to be open access. Some modifications to the current scheme may be
      needed if wider participation of marine fishers is to be achieved. These may
      include a tiered approach to certification, certification of fishers rather than
      fisheries, governmental facilitation to assist the latter and greater engagement
      with retailers and buyers rather than individual consumers. None of these changes
      will occur without constructive engagement of government, retailers, and the
      fishing industry.

PMID- 16903101
TI  - Resolving critical habitat designation failures: reconciling law, policy, and
      biology.
AB  - The US. Endangered Species Act (ESA) requires designation of critical habitat
      concurrent with species listing. The US. Fish and Wildlife Service often has not
      designated critical habitat, based on the legal exceptions in the ESA of "not
      prudent" or "not determinable." This lack of habitat designation has led to
      numerous lawsuits and court orders to designate critical habitat for listed
      species. Court-mediated implementation of critical habitat is costly and delays
      listing for at-risk species. Legal, policy, judicial, and biological issues all
      contribute to the current inability of the law as enforced to lead to timely and
      cost-effective critical habitat designation. Although increased appropriations
      and delaying critical habitat designation until recovery planning have been
      proposed as solutions, we find that it will be essential to change the critical
      habitat guidelines to a decision-analysis framework to make critical habitat
      scientifically and legally workable as a conservation

PMID- 16903102
TI  - An operational model for implementing conservation action.
AB  - The preoccupation of many conservation planners with the refinement of systematic
      assessment techniques has manifested an "implementation crisis" in conservation
      planning. This preoccupation has provided systematic assessments with well-tested
      tools (e.g., area selection algorithms) and principles (e.g., representation,
      complementarity), but our understanding of these techniques currently far exceeds
      our ability to apply them effectively to pragmatic conservation problems. The
      science is informative about where one needs to do conservation, but silent on
      how to achieve it. Operational models, defined as simplified conceptualizations
      of processes for implementing conservation action at priority conservation areas,
      are essential for guiding conservation planning initiatives because they assist
      understanding of how these processes function. Operational models developed to
      date have largely been linear, simplistic, and focused on the systematic
      assessment of biological entities. Experience in the real world indicates that
      operational models for conducting conservation planning initiatives should
      explicitly complement a systematic conservation assessment with activities that
      empower individuals and institutions (enabling) and explicitly aim to secure
      conservation action (implementation). Specifically, implementing effective
      conservation action requires that systematic assessments be integrated
      functionally with a process for developing an implementation strategy and
      processes for stakeholder collaboration while maintaining a broad focus on the
      implementation of conservation action. A suite of hallmarks define effective
      operational models (e.g., stakeholder collaboration, links with land-use
      planning, social learning, and action research). Greater development and testing
      of the practical application of operational models should lead to higher levels
      of effective implementation and alleviate the implementation crisis. Social
      learning institutions are essential for ensuring ongoing improvement in the
      development and application of operational models that deliver effective
      conservation action.

PMID- 16903103
TI  - Motivations for the restoration of ecosystems.
AB  - The reasons ecosystems should be restored are numerous, disparate, generally
      understated, and commonly underappreciated. We offer a typology in which these
      reasons--or motivations--are ordered among five rationales: technocratic, biotic,
      heuristic, idealistic, and pragmatic. The technocratic rationale encompasses
      restoration that is conducted by government agencies or other large organizations
      to satisfy specific institutional missions and mandates. The biotic rationale for
      restoration is to recover lost aspects of local biodiversity. The heuristic
      rationale attempts to elicit or demonstrate ecological principles and biotic
      expressions. The idealistic rationale consists of personal and cultural
      expressions of concern or atonement for environmental degradation, reengagement
      with nature, and/or spiritual fulfillment. The pragmatic rationale seeks to
      recover or repair ecosystems for their capacity to provide a broad array of
      natural services and products upon which human economies depend and to counteract
      extremes in climate caused by ecosystem loss. We propose that technocratic
      restoration, as currently conceived and practiced, is too narrow in scope and
      should be broadened to include the pragmatic rationale whose overarching
      importance is just beginning to be recognized. We suggest that technocratic
      restoration is too authoritarian, that idealistic restoration is overly
      restricted by lack of administrative strengths, and that a melding of the two
      approaches would benefit both. Three recent examples are given of restoration
      that blends the technocratic, idealistic, and pragmatic rationales and
      demonstrates the potential for a more unified approach. The biotic and heuristic
      rationales can be satisfied within the contexts of the other rationales.

PMID- 16903104
TI  - Impacts of alternative timber harvest practices on leaf-chewing herbivores of
      oak.
AB  - Studies of the effects of logging on Lepidoptera rarely address landscape-level
      effects or effects on larval, leaf-feeding stages. We examined the impacts of
      uneven-aged and even-aged logging on the abundance, richness, and community
      structure of leaf-chewing insects of white (Quercus alba L.) and black (Q.
      velutina L.) oak trees remaining in unharvested areas by sampling 3 years before
      and 7 years after harvest. After harvest, white oaks in uneven-aged sites had 32%
      fewer species of leaf-chewing insects than control sites. This reduction in
      species richness may have resulted from changes in microclimate (reducing plant
      quality and/or changing leaf phenology) that affected a much larger total area of
      each site than did even-aged cuts. For black oak after harvest, species richness
      in uneven- and even-aged sites increased relative to levels before harvest.
      Harvesting did not alter total insect density or community structure in the
      unlogged habitat for either oak species with one exception: insect density on
      black oak increased in the oldest forest block. Community structure of herbivores
      of black and white oaks in clearcut gaps differed from that of oaks in intact
      areas of even-aged sites. Furthermore, both richness and total insect density of
      black oaks were reduced in clearcut gaps. We suggest that low-level harvests
      alter herbivore species richness at the landscape level. Treatment effects were
      subtle because we sampled untreated areas of logged landscapes, only one harvest
      had occurred, and large temporal and spatial variation in abundance and richness
      existed. Although the effects of logging were greater in uneven-aged sites, the
      effects of even-aged management are likely to increase as harvesting continues.

PMID- 16903105
TI  - Prediction of parasite infection dynamics in primate metapopulations based on
      attributes of forest fragmentation.
AB  - Although the effects of forest fragmentation on species and ecological processes
      have been the focus of considerable research in conservation biology, our
      capacity to predict how processes will be altered and which taxonomic or
      functional groups will be most affected by fragmentation is still poor. This
      problem is exacerbated by inherent temporal and spatial variability in fragment
      attributes. To improve our understanding of this interplay, we examined how
      various fragment attributes affect one potentially important ecological process,
      parasite infection dynamics, and considered how changes in this process affect
      host metapopulations. From August 1999 to July 2003 we surveyed red colobus
      (Piliocolobus tephrosceles) metapopulations inhabiting nine fragments (1.2 to 8.7
      ha) in western Uganda to determine the prevalence and richness of strongyle and
      rhabditoid nematodes, a group of potentially pathogenic gastrointestinal
      parasites. We used noninvasive fecal flotation and sedimentation (n = 536) to
      detect parasite eggs, cysts, and larvae in colobus fecal samples. To obtain an
      index of infection risk, we determined environmental contamination with
      Oesophagostomum sp., a representative strongyle nematode, in canopy (n = 30) and
      ground vegetation plots (n = 30). Concurrently, physical (i.e., size, location,
      and topography) and biological (i.e., tree diversity, tree density, stump
      density, and colobine density) attributes were quantified for each fragment.
      Interfragment comparisons of nine potential factors demonstrated that an index of
      degradation and human presence (tree stump density) strongly influenced the
      prevalence of parasitic nematodes. Infection risk was also higher in the fragment
      with the highest stump density than in the fragment with the lowest stump
      density. These results demonstrate that host-parasite dynamics can be altered in
      complex ways by forest fragmentation and that intensity of extraction (e.g.,
      stump density) best explains these changes.

PMID- 16903106
TI  - Modeling species' distributions to improve conservation in semiurban landscapes:
      koala case study.
AB  - Models of species' distributions are commonly used to inform landscape and
      conservation planning. In urban and semiurban landscapes, the distributions of
      species are determined by a combination of natural habitat and anthropogenic
      impacts. Understanding the spatial influence of these two processes is crucial
      for making spatially explicit decisions about conservation actions. We present a
      logistic regression model for the distribution of koalas (Phascolarctos cinereus)
      in a semiurban landscape in eastern Australia that explicitly separates the
      effect of natural habitat quality and anthropogenic impacts on koala
      distributions. We achieved this by comparing the predicted distributions from the
      model with what the predicted distributions would have been if anthropogenic
      variables were at their mean values. Similar approaches have relied on making
      predictions assuming anthropogenic variables are zero, which will be unreliable
      if the training data set does not include anthropogenic variables close to zero.
      Our approach is novel because it can be applied to landscapes where anthropogenic
      variables are never close to zero. Our model showed that, averaged across the
      study area, natural habitat was the main determinant of koala presence. At a
      local scale, however anthropogenic impacts could be more important, with
      consequent implications for conservation planning. We demonstrated that this
      modeling approach, combined with the visual presentation of predictions as a map,
      provides important information for making decisions on how different conservation
      actions should be spatially allocated. This method is particularly useful for
      areas where wildlife and human populations exist in close proximity.

PMID- 16903107
TI  - Effects of restoring oak savannas on bird communities and populations.
AB  - Efforts to restore and maintain oak savannas in North America, with emphasis on
      the use of prescribed fire, have become common. Little is known, however about
      how restoration affects animal populations, especially those of birds. I compared
      the breeding densities, community structure, and reproductive success of birds in
      oak savannas maintained by prescribed fire (12 sites) with those in closed-canopy
      forests (13 sites). All sampling was conducted in Illinois (U.S.A.). Of the 31
      bird species analyzed, 12 were more common in savannas, 14 were not affected by
      habitat structure, and 5 were more common in forest habitat. The species favored
      by disturbance and restoration included Northern Bobwhites (Colinus virginianus),
      Mourning Doves (Zenaida macroura), Red-headed Woodpeckers (Melanerpes
      erythrocephalus), Indigo Buntings (Passerina cyanea), and Baltimore Orioles
      (Icterus galbula). Those more common in closed-canopy forest included Ovenbirds
      (Seiurus aurocapilla) and Wood Thrushes (Hylocichla mustelina). Few species were
      unique to one type of habitat, but overall avian community structure in oak
      savannas and closed-canopy forests was generally distinctive. Estimates of
      nesting success (derived from 785 nests) revealed that 6 of the 13 species
      considered experienced greater productivity in the savanna habitat. Rates of
      brood parasitism were unaffected by restoration and habitat structure. Within
      savannas, tract size had little effect on breeding abundances and reproductive
      success. My results illustrate that restoration techniques can significantly
      affect the ecology of constituent animal populations and communities and have key
      implications regarding avian conservation and the management of forest habitat in
      fragmented landscapes. Small patches of forest habitat that regularly function as
      population sinks may offer far better prospects for birds if they are subjected
      to disturbance and ecosystem restoration.

PMID- 16903108
TI  - Centennial decline in the trophic level of an endangered seabird after fisheries
      decline.
AB  - Coastal marine ecosystems worldwide have undergone such profound transformations
      from over-fishing that trophic interactions observed today might be artifacts of
      these changes. We determined whether the trophic level of an endangered seabird,
      the Marbled Murrelet (Brachyramphus marmoratus), has declined over the past 100
      years after the collapse of Pacific sardine (Sardinops sadax) fisheries in the
      late 1940s and the recent declines of similar fisheries in central California. We
      compared stable-isotope signatures of delta15N and delta13C in feathers of museum
      specimens collected before fisheries decline with values in murrelet feathers
      collected recently. Values of delta15N in prebreeding diets declined
      significantly, 1.4 per thousand or 38% of a trophic level, over the past century
      during cool ocean conditions and by 0.5 per thousand during warm conditions,
      whereas postbreeding values of delta15N were nearly constant. The delta13C values
      in prebreeding diets declined by 0.8 per thousand, suggesting an increased
      importance of krill in modern compared with historic prebreeding diets, but
      postbreeding diets did not change. Stable-isotope mixing models indicated that
      the proportion of energetically superior high-trophic-level prey declined
      strongly whereas energetically poor low-trophic-level and midtrophic-level prey
      increased in the prebreeding diet in cool years when murrelet reproduction was
      likely to be high. Decreased prey resources have caused murrelets to fish further
      down on the food web, appear partly responsible for poor murrelet reproduction,
      and may have contributed to its listing under the U.S. Endangered Species Act.

PMID- 16903109
TI  - Bioeconomic modeling in conservation pest management: effect of stoat control on
      extinction risk of an indigenous New Zealand passerine, Mohua ochrocephala.
AB  - Pest control is a key activity undertaken to conserve threatened and declining
      species. Although bioeconomic analysis has been used to contrast the relative
      efficiency of control strategies where pests affect economic resources, the same
      approaches have been adopted rarely in conservation settings. The Mohua (Mohoua
      ochrocephala) is an insectivorous passerine indigenous to beech (Nothofagus spp.)
      forests in New Zealand's south island. Mohua have undergone a 75% range
      contraction since stoats (Mustela erminea) (which prey on nests and nesting
      females) were introduced to the south island in the late 1800s. Mohua nests are
      particularly vulnerable when stoat abundance increases in response to eruptions
      in the density of introduced house mice (Mus musculus), which in turn respond to
      semiperiodic (4-6year) mass seeding (masting) of beech trees. Controlling stoats
      only when their abundance poses a threat to Mohua fledging success would
      theoretically maximize the efficiency with which Mohua are protected. To better
      synchronize stoat control with periods of high stoat density, control could be
      initiated according to (1) time since last control, (2) beech seedfall, (3) mouse
      abundance, or (4) stoat abundance. Monitoring the three environmental cues,
      however, incurs costs that should be taken into account when considering their
      relative efficiency I derived an empirically based stochastic model that links
      sequential change in beech seedfall, mouse, and stoat abundance to a simple
      demographic model for Mohua. I used the model to contrast the relative cost
      efficiency of achieving conservation outcomes for Mohua (specified in a quasi
      extinction framework), initiating stoat control according to these cues. The use
      of environmental cues reduced the frequency with which stoat control had to be
      undertaken to achieve Mohua conservation outcomes by more than 50%. For some
      cues, however the costs of monitoring outweighed the savings that could be
      achieved through reduced frequency of stoat control. The interplay between costs
      of monitoring environmental cues and the frequency with which stoat control had
      to be undertaken meant that the most efficient strategy was dependent on the
      conservation outcome specified for Mohua. My results demonstrate the utility of
      bioeconomic analysis in formulation of pest management strategies to achieve
      conservation outcomes.

PMID- 16903110
TI  - Modeling opportunity costs of conservation in transitional landscapes.
AB  - Conservation scientists recognize the urgency of incorporating opportunity costs
      into conservation planning. Despite this, applications to date have been limited,
      perhaps partly because of the difficulty in determining costs in regions with
      limited data on land prices and ownership. We present methods for estimating
      opportunity costs of land preservation in landscapes or ecoregions that are a
      changing mix of agriculture and natural habitat. Our approach derives from the
      literature on estimating land values as opportunity costs of alternate land uses
      and takes advantage of general availability of necessary data, even in relatively
      data-poor regions. The methods integrate probabilities of habitat conversion with
      region-wide estimates of economic benefits from agricultural land uses and
      estimate land values with a discount rate to convert annual values into net
      present values. We applied our method in a landscape undergoing agricultural
      conversion in Paraguay. Our model of opportunity costs predicted an independent
      data set of land values and was consistent with implicit discount rates of 15
      25%. Model-generated land values were strongly correlated with actual land values
      even after correcting for the effect of property size and proportion of property
      that was forested. We used the model to produce a map of opportunity costs and to
      estimate the costs of conserving forest within two proposed corridors in the
      landscape. This method can be applied to conservation planning in situations
      where natural habitat is currently being converted to market-oriented land uses.
      Incorporating not only biological attributes but also socioeconomic data can help
      in the design of efficient networks of protected areas that represent
      biodiversity at minimum costs.

PMID- 16903111
TI  - Using niche-based models to improve the sampling of rare species.
AB  - Because data on rare species usually are sparse, it is important to have
      efficient ways to sample additional data. Traditional sampling approaches are of
      limited value for rare species because a very large proportion of randomly chosen
      sampling sites are unlikely to shelter the species. For these species, spatial
      predictions from niche-based distribution models can be used to stratify the
      sampling and increase sampling efficiency. New data sampled are then used to
      improve the initial model. Applying this approach repeatedly is an adaptive
      process that may allow increasing the number of new occurrences found. We
      illustrate the approach with a case study of a rare and endangered plant species
      in Switzerland and a simulation experiment. Our field survey confirmed that the
      method helps in the discovery of new populations of the target species in remote
      areas where the predicted habitat suitability is high. In our simulations the
      model-based approach provided a significant improvement (by a factor of 1.8 to 4
      times, depending on the measure) over simple random sampling. In terms of cost
      this approach may save up to 70% of the time spent in the field.

PMID- 16903112
TI  - A multiscale method for selecting indicator species and priority conservation
      areas: a case study for broadleaved forests in Lombardy, Italy.
AB  - Our purpose was to define a quantitative and expeditious method to analyze the
      effects of processes that influence species distribution and abundance at
      different organizational scales. We considered habitat loss, the breaking apart
      of habitat patches, and habitat structural alteration critical processes that
      affect species distribution and abundance. We evaluated the effects of these
      processes by considering the response of selected indicator species to isolation
      (landscape scale), patch size and edge effect (patch scale), and habitat
      structure (plot scale). We used broadleaf forests as our case-study ecosystem and
      birds as indicator species. Faunal data came from a georeferenced, long-term,
      breeding-bird database, and environmental data were obtained from field surveys
      and land-use digital cartography Birds, grouped according to their sensitivity to
      patch isolation, patch size, edge effect, and habitat structure, indicated how
      environmental conditions affected species abundance. The most sensitive group to
      the above-mentioned processes included the Marsh Tit (Parus palustris), Nuthatch
      (Sitta curopaea), and Short-toed Treecreeper (Certhia brachydactyla). We
      evaluated the umbrella effect of these species for the conservation of the other
      co-occurring birds and found that their effectiveness varied according to the
      criterion used to select sites for protection. Site selection based on indicator
      species identified forest patches with greater species abundance than an
      alternative criterion that chose sites based on patch isolation and size, edge
      effect, and.forest structure. The alternative criterion, although not as
      efficient as indicator species, may nevertheless be useful and effective for
      conservation when faunal data are lacking and guidelines for habitat management
      or restoration are needed. Our method is applicable to other ecosystems and taxa
      because the processes we considered occur in many ecosystems and may have
      significant effects on species from all taxonomic groups.

PMID- 16903113
TI  - Adaptive decision rules for the acquisition of nature reserves.
AB  - Although reserve-design algorithms have shown promise for increasing the
      efficiency of conservation planning, recent work casts doubt on the usefulness of
      some of these approaches in practice. Using three data sets that vary widely in
      size and complexity, we compared various decision rules for acquiring reserve
      networks over multiyear periods. We explored three factors that are often
      important in real-world conservation efforts: uncertain availability of sites for
      acquisition, degradation of sites, and overall budget constraints. We evaluated
      the relative strengths and weaknesses of existing optimal and heuristic decision
      rules and developed a new set of adaptive decision rules that combine the
      strengths of existing optimal and heuristic approaches. All three of the new
      adaptive rules performed better than the existing rules we tested under virtually
      all scenarios of site availability, site degradation, and budget constraints.
      Moreover, the adaptive rules required no additional data beyond what was readily
      available and were relatively easy to compute.

PMID- 16903114
TI  - Global warming and extinctions of endemic species from biodiversity hotspots.
AB  - Global warming is a key threat to biodiversity, but few researchers have assessed
      the magnitude of this threat at the global scale. We used major vegetation types
      (biomes) as proxies for natural habitats and, based on projected future biome
      distributions under doubled-CO2 climates, calculated changes in habitat areas and
      associated extinctions of endemic plant and vertebrate species in biodiversity
      hotspots. Because of numerous uncertainties in this approach, we undertook a
      sensitivity analysis of multiple factors that included (1) two global vegetation
      models, (2) different numbers of biome classes in our biome classification
      schemes, (3) different assumptions about whether species distributions were biome
      specific or not, and (4) different migration capabilities. Extinctions were
      calculated using both species-area and endemic-area relationships. In addition,
      average required migration rates were calculated for each hotspot assuming a
      doubled-CO2 climate in 100 years. Projected percent extinctions ranged from <1 to
      43% of the endemic biota (average 11.6%), with biome specificity having the
      greatest influence on the estimates, followed by the global vegetation model and
      then by migration and biome classification assumptions. Bootstrap comparisons
      indicated that effects on hotpots as a group were not significantly different
      from effects on random same-biome collections of grid cells with respect to biome
      change or migration rates; in some scenarios, however, botspots exhibited
      relatively high biome change and low migration rates. Especially vulnerable
      hotspots were the Cape Floristic Region, Caribbean, Indo-Burma, Mediterranean
      Basin, Southwest Australia, and Tropical Andes, where plant extinctions per
      hotspot sometimes exceeded 2000 species. Under the assumption that projected
      habitat changes were attained in 100 years, estimated global-warming-induced
      rates of species extinctions in tropical hotspots in some cases exceeded those
      due to deforestation, supporting suggestions that global warming is one of the
      most serious threats to the planet's biodiversity.

PMID- 16903115
TI  - Designing large-scale conservation corridors for pattern and process.
AB  - A major challenge for conservation assessments is to identify priority areas that
      incorporate biological patterns and processes. Because large-scale processes are
      mostly oriented along environmental gradients, we propose to accommodate them by
      designing regional-scale corridors to capture these gradients. Based on
      systematic conservation planning principles such as representation and
      persistence, we identified large tracts of untransformed land (i.e., conservation
      corridors) for conservation that would achieve biodiversity targets for pattern
      and process in the Subtropical Thicket Biome of South Africa. We combined least
      cost path analysis with a target-driven algorithm to identify the best option for
      capturing key environmental gradients while considering biodiversity targets and
      conservation opportunities and constraints. We identified seven conservation
      corridors on the basis of subtropical thicket representation, habitat
      transformation and degradation, wildlife suitability, irreplaceability of
      vegetation types, protected area networks, and future land-use pressures. These
      conservation corridors covered 21.1% of the planning region (ranging from 600 to
      5200 km2) and successfully achieved targets for biological processes and to a
      lesser extent for vegetation types. The corridors we identified are intended to
      promote the persistence of ecological processes (gradients and fixed processes)
      and fulfill half of the biodiversity pattern target. We compared the conservation
      corridors with a simplified corridor design consisting of a fixed-width buffer
      along major rivers. Conservation corridors outperformed river buffers in seven
      out of eight criteria. Our corridor design can provide a tool for quantifying
      trade-offs between various criteria (biodiversity pattern and process,
      implementation constraints and opportunities). A land-use management model was
      developed to facilitate implementation of conservation actions within these
      corridors.

PMID- 16903116
TI  - Significance of sighting rate in inferring extinction and threat.
AB  - We are now entering a time of immense environmental upheaval in which,
      increasingly, experts are required to provide conservation assessments.
      Quantitative assessment of trends in species' range and abundance is costly,
      requiring extensive field studies over a long period of time. Unfortunately, many
      species are only known through a few "chance" sightings or a handful of
      specimens, and therefore extinction may be even harder to ascertain. Several
      methods have been proposed for estimating the probability of extinction. However
      comparison within and between species is difficult because of variations in
      sighting rates. We applied a probabilistic method that incorporates sighting rate
      to the sighting record of Vietnamese slipper orchids (Paphiopedilum). The method
      generates a probability that another sighting will occur given the previous
      sighting rate and the time since last observation. This allows greater
      comparability between species discovered at different times. Its predictions were
      more highly correlated with the World Conservation Union criteria than previous
      methods. Trends in data collection and the political climate of a country, which
      affects access to material, are important potential sources of variation that
      affect sighting rates. A lack of understanding of the process by which data are
      generated makes inferring extinction from sighting records difficult because
      extinction status depends on how the sighting rate varies. However such methods
      allow rapid conservation prioritization of taxa that are poorly known and would
      otherwise go unassessed.

PMID- 16903117
TI  - Remote forest refugia for Fijian wildlife.
AB  - On Pacific islands non-native rats and mongooses threaten many native species. In
      Fiji we compared visitation rates of rats and mongooses at bait stations and
      measured biomass of leaf-litter invertebrates to assess the relative predation
      pressure from these species in forest areas at different distances from the
      forest edge. Forest areas over 5 km from the forest edge had significantly fewer
      baits encountered by rats or mongooses than did natural forest areas nearer
      agricultural and urban habitats. Remote forest areas may function as a last
      refuge for island species threatened by predation from non-native rats and
      mongooses. The biomass of leaf-litter invertebrates in remote forest areas was
      higher indicating a refuge effect for some taxa targeted by rats and mongooses.
      Protection of the few remaining large blocks of natural forests on Pacific
      islands may be the most cost-effective approach for conserving many island
      endemics threatened by rats and mongooses. Logging roads can compromise this
      refuge effect by acting as dispersal routes for rats into natural forests.

PMID- 16903118
TI  - Theories about consensus-based conservation.
AB  - "Conservation and the Myth of Consensus" (Peterson et al. 2005) levels several
      serious indictments against consensus-based approaches to environmental decision
      making. Namely, the authors argue that consensus processes (1) reinforce apathy
      and ignorance of conservation issues; (2) legitimize damage to the environment;
      (3) quash public debate about conservation; (4) solidify the existing balance of
      power in favor of prodevelopment forces; and (5) block progress toward an
      ecologically sustainable future. Careful scrutiny of consensus-based approaches
      is important, especially considering their surging use in conservation policy. In
      the spirit of advancing the debate further, I review some of the limitations of
      the essay and its modes of inquiry.

PMID- 16903119
TI  - Why conservation needs dissent.

PMID- 16903120
TI  - Biodiversity indicators based on trends in conservation status: strengths of the
      IUCN Red List Index.

PMID- 16903121
TI  - Biodiversity indicators based on trends in conservation status: advancing the
      science.

PMID- 16903122
TI  - Mass cetacean strandings-a plea for empiricism.

PMID- 16903123
TI  - Working memory and information processing speed in children with myelomeningocele
      and shunted hydrocephalus: analysis of the children's paced auditory serial
      addition test.
AB  - Working memory and information processing speed were examined in children with
      myelomeningocele and shunted hydrocephalus using the Children's Paced Auditory
      Serial Addition Test (CHIPASAT). The CHIPASAT was administered to 31 children
      with myelomeningocele and shunted hydrocephalus and 27 healthy siblings, all
      between 8 and 15 years of age. They also completed other standardized measures of
      working memory and processing speed. Children with myelomeningocele made fewer
      correct responses than siblings, although the magnitude of group differences
      declined as the rate of stimulus presentation increased. Children with
      myelomeningocele also made fewer consecutive correct responses and were more
      likely to provide correct but nonconsecutive responses, suggesting that they
      responded in a way that circumvents the working memory demands of the task.
      Standardized measures of processing speed and working memory accounted for
      significant variance in CHIPASAT performance after controlling for age, group
      membership, math skill, and general intellectual functioning. The results
      indicate that children with myelomeningocele and shunted hydrocephalus display
      deficits in working memory and information processing speed, and suggest that the
      CHIPASAT may provide a valid measure of these skills.

PMID- 16903124
TI  - Developmental dyspraxia is not limited to imitation in children with autism
      spectrum disorders.
AB  - Impaired imitation of skilled gestures is commonly reported in autism. Questions,
      however, remain as to whether impaired imitation is associated with a more
      generalized deficit in performance of gestures consistent with a dyspraxia and
      whether the pattern of errors differs from that observed in typically developing
      children. To address these questions, praxis in 21 high-functioning children with
      autism spectrum disorders (ASD) was compared with 24 typically developing
      controls using a traditional approach in which performance was evaluated through
      detailed examination of error types. Children with ASD produced significantly
      fewer correct responses not only during Gesture to Imitation, but also during
      Gesture to Command and with Tool Use. The pattern of errors in ASD was similar to
      that of controls with spatial errors being most common in both groups; however,
      body-part-for-tool errors were more common in children with ASD, suggesting
      dyspraxia is not entirely attributable to motor deficits. The findings suggest
      that autism is associated with a generalized praxis deficit, rather than a
      deficit specific to imitation. In a developmental disorder such as autism, the
      findings may reflect abnormalities in frontal/parietal-subcortical circuits
      important for acquisition (i.e., learning) of sensory representations of movement
      and/or the motor sequence programs necessary to execute them.

PMID- 16903125
TI  - Spatial and temporal order memory in Korsakoff patients.
AB  - This study directly compared how well Korsakoff patients can process spatial and
      temporal order information in memory under conditions that included presentation
      of only a single feature (i.e., temporal or spatial information), combined
      spatiotemporal presentation, and combined spatiotemporal order recall. Korsakoff
      patients were found to suffer comparable spatial and temporal order recall
      deficits. Of interest, recall of a single feature was the same when only spatial
      or temporal information was presented compared to conditions that included
      combined spatiotemporal, presentation and recall. In contrast, control
      participants performed worse when they have to recall both spatial and temporal
      order compared to when they have to recall only one of these features. These
      findings together indicate that spatial and temporal information are not
      automatically integrated. Korsakoff patients have profound problems in coding the
      feature at hand. Moreover, their lower recall of both features at the same time
      suggests that Korsakoff patients are impaired in binding different contextual
      attributes together in memory.

PMID- 16903126
TI  - Differential influences of prism adaptation on reflexive and voluntary covert
      attention.
AB  - Recent research has demonstrated some beneficial effects in patients with neglect
      using rightward shifting prismatic lenses. Despite a great deal of research
      exploring this effect, we know very little about the cognitive mechanisms
      underlying prism adaptation in neglect. We examined the possibility that prism
      adaptation influences visual attention by having healthy participants complete
      either a reflexive or a voluntary covert visual attention cuing paradigm before
      and after adaptation to leftward, rightward, or sham (no shift) prisms. The
      results for reflexive orienting demonstrated that a subset of participants with
      large cuing effects before prism adaptation were faster to reorient attention
      away from an invalid cue on the side of space opposite the prismatic shift post
      adaptation. For voluntary orienting, left prisms increased the efficiency of
      voluntary attention in both left and right visual space in participants with a
      small cuing effect before prism adaptation. In contrast, right prisms decreased
      the efficiency of voluntary attention in both left and right space for
      participants with a large cuing effect before prism adaptation. No significant
      effects were observed in the sham prism groups. These results suggest that prism
      adaptation may exert a variety of influences on attentional orienting mechanisms.

PMID- 16903127
TI  - Demographic and cognitive predictors of long-term psychosocial outcome following
      traumatic brain injury.
AB  - Demographic factors and cognitive impairment have been found previously to have
      associations with outcome after brain injury. Kendall and Terry (1996) suggest
      that preinjury psychosocial functioning, neurological factors, and cognitive
      impairment have a direct relationship with multidimensional psychosocial
      adjustment, but that cognitive impairment also has an indirect relationship by
      means of the mediation of appraisal and coping variables. The aim of this study
      was to explore these theoretical relationships at very late stages of recovery
      after brain injury. A total of 131 participants who were more than 10 years after
      injury (mean = 15.31 yr) completed a neuropsychological assessment, plus outcome
      measures that included employment status, community integration, life
      satisfaction, quality of life (QoL), and emotion. Results indicated that injury
      severity was predictive of life satisfaction; gender and relationship status
      predicted community integration; and age at injury predicted employment status.
      Impairment in working memory directly predicted all outcomes except QoL and
      anxiety. An indirect relationship was also evident between working memory, life
      satisfaction, and depression. Results partially support Kendall and Terry's model
      but the variables that significantly influence outcome seem to be determined by
      the outcome dimensions selected.

PMID- 16903128
TI  - Evaluating a theory of stress and adjustment when predicting long-term
      psychosocial outcome after brain injury.
AB  - Kendall and Terry (1996) include many psychosocial predictors in their
      theoretical model that explains individual differences in psychosocial adjustment
      (Lazarus & Folkman, 1984). The model depicts appraisal and coping variables as
      mediating relationships between situation factors, environmental and personal
      resources, and multidimensional outcome. The aim of this study was to explore
      these theoretical relationships at very late stages of recovery from traumatic
      brain injury. A total of 131 participants who were more than 10 years post-injury
      (mean = 15.31 years) completed several psychosocial measures relating to outcome
      dimensions comprising employment, community integration, life satisfaction,
      quality of life (QoL), and emotion. There was no evidence that appraisal and
      coping variables mediated relationships between psychosocial and any of the
      outcome variables. However, when appraisal and coping variables were combined
      with psychosocial variables as direct predictors of outcome, every outcome except
      employment status was reliably predicted, accounting for between 31 and 46% of
      the variance. Personality significantly influenced all predicted outcomes. Self
      efficacy contributed to the prediction of all outcomes except QoL. Data did not
      support for the theory of stress and adjustment as a framework for explaining the
      nature of predictive relationships between psychosocial variables and very long
      term, multidimensional outcome after brain injury.

PMID- 16903129
TI  - The neuropsychological profile of symptomatic AIDS and ADC patients in the pre
      HAART era: a meta-analysis.
AB  - It remains essential to document the neuropsychological profile of acquired
      immunodeficiency syndrome (AIDS) dementia complex (ADC) and minor forms human
      immunodeficiency virus (HIV)-associated neurocognitive impairment by quantifying
      the magnitude of impairment across eras of treatment. Indeed, with the
      introduction of the highly active antiretroviral therapy (HAART), there is
      evidence of changes in aspects of ADC. To allow quantitative and qualitative
      comparisons with the HAART era studies, we developed a summary of
      neuropsychological performance acquired in pre-HAART era studies in advanced HIV
      infection and ADC. Using a meta-analytical procedure and a test nomenclature that
      accounts for task complexity, we found that individuals with symptomatic
      infection (but no AIDS) demonstrated a global mild level of cognitive impairment,
      except for the domains complex attention/psychomotor speed, motor coordination,
      and learning, which showed moderate impairment. Individuals with AIDS
      demonstrated a global moderate level of cognitive impairment with a predominance
      of deficits in attention, complex attention/psychomotor speed, learning, motor
      coordination, with additional deficits in verbal memory and reasoning.
      Individuals with ADC demonstrated the most severe cognitive disturbances in
      domains of learning, motor coordination, with additional deficits in veibal
      fluency and verbal memory. Moderate impairment was evidenced in domains of
      complex attention/psychomotor speed, whereas naming and visuospatial functions
      were relatively preserved. The profile of deficits in ADC suggests that it may
      not be only interpreted as a worsening form of the impairment that is seen in the
      AIDS and symptomatic stages of HIV disease but that there are also additional
      deficits suggestive of an alternate pathogenetic process(es).

PMID- 16903130
TI  - Global/local scoring modifications for the Rey-Osterrieth Complex Figure:
      relation to unilateral temporal lobe epilepsy patients.
AB  - Observation of figural reproductions of right temporal lobe epilepsy (RTLE)
      patients have revealed overall configuration errors, whereas in left temporal
      lobe epilepsy (LTLE) patients, the global aspect of performance is generally
      preserved. This study compared performance of individuals with temporal lobe
      epilepsy (LTLE, n=83; RTLE, n=63) on a global/local modification of the Rey
      Osterrieth Complex Figure Test (RCFT). In Phase I, neuropsychologists (n=6) and
      neuropsychology fellows (n=3) completed a survey identifying the global and local
      aspects of the RCFT. Questionnaire responses were used to categorize a list of
      global and local items (five global, five local) for re-scoring the protocols of
      TLE patients during study Phase II. Results showed that the RTLE and LTLE groups
      were not differentiated according to the global or local indices F(1,141) = .385;
      p = not significant. There were lower local scores for both groups in the copy
      F(1,142) = 5.23; p = .024, immediate F(1,142) = 445.26; p < .001, and delay
      trials F(1,142) = 427.82; p < .001, indicating less retention of local
      information over time. Results suggest general declines in figural memory for
      local stimulus properties in both unilateral TLE groups. However, this
      relationship was weakened after controlling for global and local item
      verbalizability.

PMID- 16903131
TI  - Is adaptation of the word accentuation test of premorbid intelligence necessary
      for use among older, Spanish-speaking immigrants in the United States?
AB  - Adaptations of the National Adult Reading Test (NART) for assessing premorbid
      intelligence in languages other than English requires (a) generating word-items
      that are rare and do not follow grapheme-to-phoneme mappings common in that
      language, and (b) subsequent validation against a cognitive battery normed on the
      population of interest. Such tests exist for Italy, France, Spain, and Argentina,
      all normed against national versions of the Wechsler Adult Intelligence Scale.
      Given the varieties of Spanish spoken in the United States, the adaptation of the
      Spanish Word Accentuation Test (WAT) requires re-validating the original word
      list, plus possible new items, against a cognitive battery that has been normed
      on Spanish-speakers from many countries. This study reports the generation of 55
      additional words and revalidation in a sample of 80 older, Spanish-dominant
      immigrants. The Bateria Woodcock-Munoz Revisada (BWM-R), normed on Spanish
      speakers from six countries and five U.S. states, was used to establish criterion
      validity. The original WAT word list accounted for 77% of the variance in the BWM
      R and 58% of the variance in Ravens Colored Progressive Matrices, suggesting that
      the unmodified list possesses adequate predictive validity as an indicator of
      intelligence. Regression equations are provided for estimating BWM-R and Ravens
      scores from WAT scores.

PMID- 16903132
TI  - Estrogen and performance in recognition memory for olfactory and visual stimuli
      in females diagnosed with Alzheimer's disease.
AB  - Patients with Alzheimer's disease (AD) exhibit a deficit in episodic recognition
      memory for odors. It is hypothesized that the higher rate of AD in women may be
      due to estrogen-deprivation in postmenopausal women. Research suggests that
      estrogen may help to minimize cognitive decline in AD as well as postmenopausal
      olfactory loss. The current study examined the effects of estrogen replacement
      therapy (ERT) on performance of a recognition memory task for olfactory and
      visual stimuli in women AD patients. Participants included 24 women AD patients
      who were ERT users and 77 women AD patients who never used ERT. Compared with the
      ERT non-users, the ERT users committed significantly less false-positive memory
      errors for olfactory stimuli, whereas performance for visual stimuli did not
      differentiate between ERT users and non-users. The results suggest benefits of
      ERT could help ameliorate the earliest symptoms of AD, olfactory dysfunction, and
      memory impairment.

PMID- 16903133
TI  - Executive dysfunction in substance dependent individuals during drug use and
      abstinence: an examination of the behavioral, cognitive and emotional correlates
      of addiction.
AB  - Increasing evidence indicates that substance-dependent individuals (SDI) are
      impaired in executive control tasks relying on different systems within the
      prefrontal cortex (PFC). Three different functional systems have been described:
      the dorsolateral prefrontal cortex (DLPC), orbitofrontal cortex (OFC), and
      anterior cingulate cortex (ACC) circuits. Dysfunction within each PFC system is
      associated with different behavioral, cognitive, and emotional abnormalities. Few
      studies have conducted an exhaustive examination of all these different factors
      in SDI. In this study, SDI (including alcohol, cocaine, and methamphetamine
      polysubstance users, n=35) were compared with healthy controls (n=36) on a series
      of behavioral (Frontal Systems Behaviour Scale, FrSBe), cognitive (N-back, Go-No
      Go, and Wisconsin Card Sorting Tasks), and emotional (International Affective
      Picture System, IAPS) tasks, each of which was thought to tax a different
      component of these PFC functional systems. SDI showed greater behavioral problems
      in the apathy, disinhibition, and executive dysfunction subscales of the FrSBe.
      Behavioral deficits were significantly associated with several real-life domains
      in which SDI typically have problems. SDI also showed poorer performance on
      cognitive tests of working memory, response inhibition and mental flexibility,
      and abnormal processing of affective images from the IAPS. Cognitive, behavioral,
      and emotional measures were moderately correlated.

PMID- 16903134
TI  - Spatial negative priming in early Alzheimer's disease: evidence for reduced
      cognitive inhibition.
AB  - Some studies of negative priming and other tasks assumed to reflect inhibitory
      functions suggest a decline in inhibitory processes in Alzheimer's disease.
      However, none of the measures used in previous studies can be interpreted as an
      unambiguous reflection of distractor inhibition. The present study investigates
      whether reductions in negative priming associated with Alzheimer's disease
      reflect reduced distractor inhibition, rather than perceptual review processes.
      Individuals with early Alzheimer's disease were predicted to show reduced
      negative priming on a spatial localization task designed to provide an
      unambiguous measure of distractor inhibition. Sixteen clinical participants
      showed significantly less negative priming than old and young healthy control
      groups, which is interpreted as evidence for reduced distractor inhibition in
      early dementia. A second analysis indicated that, within the clinical sample
      only, negative priming effect size was significantly correlated with prime trial
      response speed. Clinical participants showing the least negative priming were
      slower to respond to an initial stimulus. The results may mean that people with
      early Alzheimer's disease have a reduced capacity to use excitatory as well as
      inhibitory processes in selection.

PMID- 16903135
TI  - Neurocognitive consequences of HIV in southern India: a preliminary study of
      clade C virus.
AB  - The neurocognitive impact of the clade C viral strain of human immunodeficiency
      virus (HIV) has not been determined. The purpose of this study was to examine
      neurocognitive function in southern India among individuals with the clade C
      virus with advanced HIV. A battery of cognitive tasks sensitive to the effects of
      HIV on brain function was translated and administered in Tamil and Telegu, two
      widely spoken languages in southern India. A sample of 30 treatment-naive HIV
      positive individuals with a median CD4 cell count of 97, and 30 age and education
      matched healthy controls obtained from the same region of India, were included in
      the study. Results revealed significant differences on most cognitive tests, with
      lower performances obtained by the HIV-positive individuals. These results
      suggest that cognitive difficulties are present among individuals with the clade
      C virus in India, with as many as 56% of the patients with advanced HIV meeting
      the criterion for impairment in two cognitive domains. Additional study is needed
      to determine if clade C HIV infection is more or less prone to cause
      neurocognitive deficit than the clade B virus. Furthermore, the impact of
      antiretroviral therapy on neurocognitive dysfunction in clade C virual infection
      needs to be determined.

PMID- 16903136
TI  - Set shifting deficit in anorexia nervosa.
AB  - Anorexia nervosa (AN) is a severe mental illness characterized in part by rigid
      thinking and ritualized behaviors involving eating and weight. Cognitive rigidity
      may play a role in the perpetuation of symptoms, and may provide information as
      to important brain-based abnormalities. Neuropsychological studies of patients
      with AN have shown cognitive dysfunction, but few have focused on cognitive
      flexibility. This study assessed set shifting in patients with AN, as a measure
      of cognitive flexibility. In this study, 15 patients with AN were compared with
      11 healthy controls using a neuropsychological battery including the Wisconsin
      Card Sort Test (WCST). While patients with AN did not differ from controls on 5
      measures of neuropsychological function, they made significantly more
      perseverative errors on the WCST, indicating a problem in set shifting. This
      finding suggests that patients with AN have a specific neurocognitive abnormality
      that may play a role in the development and persistence of this disorder.

PMID- 16903137
TI  - Retention weighted recall improves discrimination of Alzheimer's disease.
AB  - Impaired recall for early items (primacy) and late items (recency) on word list
      recall tests are seen in Alzheimer's disease (AD). We compared conventional
      scoring on the Telephone Instrument for Cognitive Status (TICS) recall list with
      scorings based on retention-weighted recall (RWR: each item weighted by its
      serial position) in older adults participating in a community-based aging study.
      Subjects with mild AD (N=18) did not differ from those without dementia (N=231)
      with respect to recency (46% vs. 59%, p = 0.2), but had impaired primacy (2% vs.
      39%, p < .001) on word recall on the TICS. RWR scoring improved the effect size
      (1.52 SD) compared to conventional scoring (1.08 SD). With a fixed sensitivity of
      85%, specificity was lower using conventional scoring (56%) than RWR (76%)
      scoring. Our findings suggest that optimized RWR scoring of word list free recall
      can improve detection of mild AD compared to conventional scoring.

PMID- 16903138
TI  - Ultrastructure of the central nervous system: the basics.
AB  - Since the articles in this supplement describe ultrastructural changes in
      diseases of the nervous system, for better understanding of these papers dealing
      with pathology of the this system, basic elements of the ultrastructure of the
      central nervous system are presented in this survey. Description of the fine
      structure of cells and fibres of the central nervous system presented below is
      based on classical textbooks as well as on the authors' personal experience. The
      details of ultrastructure of nerve cells (their nucleus and cytoplasm, including
      cell organelles: abundant granular endoplasmic reticulum, prominent Golgi
      apparatus, mitochondria, lysosomes, as well as other cell components including:
      neurofilaments, lipid droplets, multivesicular bodies, lipid droplets, lipofuscin
      granules, and in some cells melanin granules, and also cell processes), the
      interneuronal chemical synapses (specialized site of interneuronal communication)
      as well as all types of neuroglial cells (a class of non-neuronal supporting
      cells): astrocytes (fibrous and protoplasmic), oligodendrocytes, and microglia
      neuroglial cells are described.

PMID- 16903139
TI  - A virus behind the mask of prions?
AB  - The prion notion, that a host-encoded protein reacts with itself to become an
      infectious entity, has become highly favoured as the causal agent in
      transmissible encephalopathies (TSEs) such as endemic scrapie of sheep, epidemic
      bovine encephalopathy (BSE), and rare forms of human Creutzfeldt-Jakob Disease
      (CJD). Much of the claimed "wealth of data" supporting the notion of prions,
      however, has been irreproducible as well as contradicted by many experimental
      observations. By 1989, for example, it was already shown that the "infectious
      prion conformation" could be eliminated without altering either infectivity or
      agent strain characteristics. Efforts to make the prion protein infectious also
      continue to fail. All the biological features of TSEs fit better with a
      conventional viral particle. Furthermore, structural data point to a spherical
      infectious particle of approximately 25 nm that contains a genome of 1-4 kb in
      length and probably encodes its own protective nucleocapsid. These viral features
      can account for the observed host recognition of TSE agents as foreign. Although
      recognised, TSE agents, like many conventional viruses, can hide in a latent
      state for many years in lymphoreticular tissues. Previous predictions made by
      this parsimonious viral interpretation have been accurate, whereas the prion
      hypothesis has been confounded by several inexplicable realities that have
      emerged. Recently developed TSE tissue culture models offer a way of identifying
      rapidly the intrinsic and strain-specific agent molecules so needed for diagnosis
      and prevention.

PMID- 16903140
TI  - Clinical findings and diagnostic tests in Creutzfeldt-Jakob disease and variant
      Creutzfeldt-Jakob disease.
AB  - Sporadic Creutzfeldt-Jakob disease (sCJD) is a rare transmissible disease caused
      by accumulation of pathological prion protein in the CNS. sCJD typically affects
      patients in their sixties. The median disease duration in sCJD (6 months) is
      shorter than in variant Creutzfeldt-Jakob disease (vCJD) (14 months). The
      clinical diagnosis in sCJD is supported by the detection of periodic sharp and
      slow wave complexes (PSWC) in the electroencephalogram, 14-3-3 proteins in the
      cerebrospinal fluid (CSF) and hyperintense basal ganglia on magnetic resonance
      imaging (MRI). In contrast to sCJD, hyperintensities in the posterior pulvinar
      (the "pulvinar sign") are seen in vCJD. Different sCJD subtypes characterised by
      distinct neuropathological lesion profiles, clinical features and codon 129
      genotype of the prion protein gene (PRNP) are described, together with the type
      with a proteinase K-resistant core of the prion protein. The sensitivity of
      diagnostic tests varies considerably in different sCJD subtypes. Alzheimer 's
      disease and Lewy body dementia are the most frequent differential diagnoses in
      elderly patients, while chronic inflammatory CNS disorders have to be considered
      in younger patients.

PMID- 16903141
TI  - An outline of the neuropathology of transmissible spongiform encephalopathies
      (prion diseases).
AB  - We review here the basic neuropathology of transmissible spongiform
      encephalopathies (TSE) or prion diseases. The classic hallmark of TSE
      neuropathology is a combination (in different proportions in different diseases)
      of spongiform change, astrocytosis, neuronal loss and amyloid plaques.
      Immunohistochemically, accumulation of the abnormal isoform of prion protein
      (PrP(sc) or PrP(d)) is regarded as a diagnostic for TSE. We also review the
      peculiarities of kuru, variant Creutzfeldt-Jakob disease and Gerstmann-Straussler
      Scheinker disease.

PMID- 16903142
TI  - Spongiform change--an electron microscopic view.
AB  - Spongiform change is a hallmark of transmissible spongiform encephalopathies
      (TSEs) in prion diseases. They are defined as small round or oval empty spaces in
      the neuropil. When confluent, they merge to form "morula-like" structures. Their
      neuroanatomical distribution and grading within each of defined neuroanatomical
      areas underlie the lesion profile method used to discriminate strains in rodents
      and in cattle. Ultrastructurally, vacuoles develop within neuronal elements. They
      are membrane-bound and contain secondary vacuoles and "curled" membrane
      fragments. Separate type of vacuoles are those develop within myelin sheath.
      Those vacuoles develop through complicated opening at the major-dense and
      intraperiod lines. The histogenesis of spongiform vacuoles is unclear and the
      only hypothesis that they develop through the formation of abnormal configuration
      of plasma membranes (ACPMs) has never been substantiated. We suggested that
      vacuoles may develop through process of autophagy.

PMID- 16903143
TI  - Astrocytes in transmissible spongiform encephalopathies (prion diseases).
AB  - Astrocytosis is one of the hallmarks of neuropathology of transmissible
      spongiform encephalopathies (TSEs) or prion diseases. In this review, we
      summarize data on astrocytic reaction, including naturally occurring or
      experimentally induced TSEs. A particular form of astrocytic reaction is known as
      gliocytosis and it is typical for experimental scrapie in mouse or in hamsters.
      Also, astrocytes participate in the formation of amyloid plaques. An interesting
      interaction between astrocytes and oligodendrocytes is discussed in detail as
      well as a particular form of astrocytic reaction in panencephalopathic form of
      TSEs.

PMID- 16903144
TI  - Mechanisms of neuronal death in transmissible spongiform encephalopathies.
AB  - The premature primary death of nerve cells is a basic feature of transimissible
      spongiform encephalopathies (TSEs) or prion diseases and other neurodegenerative
      disorders, although the cellular pathways leading to this neuronal loss are not
      entirely clear. Moreover, the question of whether there is a direct relation
      between the deposits of PrP(d) and the loss of neurons still remains a matter for
      conjecture. According to established classification, three types of programmed
      cell death during morphogenesis are discriminated: (1) apoptosis, (2) autophagy
      and (3) cytoplasmic cell death. Apoptosis has become the most popular concept of
      cell death in neurodegeneration. However, there is no direct and convincing
      evidence of apoptosis of nerve cells in most neurodegenerative diseases. Although
      there is strong evidence that autophagy is a common ultrastructural feature of
      TSEs, it is still unclear how the autophagy contributes to the overall pathology
      and, especially, to the neuronal loss underlying prion diseases. There are no
      data on cytoplasmic cell death in prion diseases. The contrasting data and lack
      of consistent molecular basis of some types of cell death leave unanswered the
      question of which type of cell death is responsible for neuronal loss in TSEs.
      However, recently developed techniques and the careful examination of the
      molecular processes leading to different types of cell death should provide the
      answer in future.

PMID- 16903145
TI  - Tubulovesicular structures--the ultrastructural hallmark for transmissible
      spongiform encephalopathies or prion diseases.
AB  - Tubulovesicular structures (particles--TVS) are the only ultrastructural marker
      for all transmissible spongiform encephalopathies (TSEs) or prion disease as seen
      by thin section electron microscopy. The latter is stressed as opposed to
      negative-staining techniques. TVS are spheres or short rods of approximately 27
      35 nm in diameter. What is particularly interesting, this size of TVS is also the
      size of filter cut-off as judged from ultrafiltration studies and the size of the
      smallest infectious unit as recently estaimated. TVS have been found in all
      naturally occurring and experimentally induced TSEs, including variant
      Creutzfeldt-Jakob disease and human familial TSEs--fatal familial insomnia and
      Gerstmann-Straussler-Scheinker disease. In longitudinal studies, the number of
      neuronal processes containing TVS correlates roughly with the incubation period
      and with infectivity. Hence, they are readily found in hamsters infected with the
      263K strain of scrapie but it is very difficult to find them in human TSEs where
      titre is lower. The composition of TVS is unknown but they are not composed of
      PrP. Their consistent presence in all TSEs suggests the role at least of TSE
      pathogenesis.

PMID- 16903146
TI  - Amyloid plaques in transmissible spongiform encephalopathies (prion diseases).
AB  - Amyloid plaques are encountered in all cases of kuru and Gerstmann-Straussler
      Scheinker disease (GSS) and in some 10-15% of sporadic Creutzfeldt-Jakob disease
      (sCJD) cases. In variant Creutzfeldt-Jakob (vCJD) the particular type of plaque
      known as "florid" or "daisy" plaque exists in 100% of cases. By electron
      microscopy several types of amyloid plaque were delineated, corresponding to
      those seen by PrP immunohistochemistry. Unicentric "kuru" plaques consisted of
      stellate arrangements (stars or cores) of amyloid bundles emanating from a dense
      interwoven centre. A proportion of kuru plaques formed very dense stars,
      reminiscent of sea urchins in shape. Others presented a looser pattern. Amyloid
      stars were enveloped by astrocytic processes. High-power electron micrographs
      revealed that amyloid bundles were concealed within grooves of obscure cellular
      origin. Interestingly, basement membranes lined with electron-dense material were
      observed at the periphery of many amyloid plaques of GSS. Dystrophic neurites
      were seen only rarely. Microglial cells formed a significant part of the amyloid
      plaques. Occasionally clusters composed of several kuru plaques were found. These
      were intermediate forms to multi-centric plaques, which consisted of several
      merging stellate cores. Smaller amyloid deposits surrounded larger cores. In
      contrast to the kuru plaques, associated with a limited number of dystrophic
      neurites (DN), numerous such structures were seen at the periphery. The DN were
      filled with abnormal organelles such as electron-dense bodies, multi-vesicular
      bodies and multilamellar bodies and thus were indistinguishable from those seen
      in scrapie and CJD or Alzheimer's disease, except that they did not contain
      paired helical filaments (PHF). Instead, piled neurofilaments were often detected
      in the centres of DN. Similar DN were observed but these were not associated with
      any plaques. The last and, by the same token, the rarest type of plaque was the
      purely neuritic plaque. These consisted of large areas filled with DN of
      different sizes and shapes (sometimes bizarre) but not amyloid bundles.
      Analogously to the kuru and multi-centric plaques, astrocytic processes were
      observed at the periphery. By means of light microscopy and semi-thin (1 microm)
      sections discrete PrP-immunopositive plaques were observed (data not shown), in
      the subependymal region but not in the deep brain neuroparenchyma, in both 263K
      and 22C-H scrapie-infected hamster brains. These plaques were not discernible by
      routine haematoxylin and eosin staining. Ultrastructurally, plaques were
      recognised as areas of low electron density containing haphazardly-oriented
      fibrils which, when immunogold techniques were applied, were heavily decorated
      with PrP-conjugated gold particles.

PMID- 16903147
TI  - Gerstmann-Straussler-Scheinker disease. I. Human diseases.
AB  - Gerstmann-Straussler-Scheinker disease (GSS) is a slowly progressive hereditary
      autosomal dominant disease (OMIM: 137440) and the first human transmissible
      spongiform encephalopathy (TSE) in which a mutation in a gene encoding for prion
      protein (PrP) was discovered. Its true prevalence is difficult to estimate but
      figures within the range of 1-10/100,000,000 are quoted. GSS is defined as a
      neurodegenerative disease "in family with dominantly inherited progressive ataxia
      and/or dementia): encephalo(myelo)pathy with multi-centric PrP plaques". In this
      review, we summarise data on all the families with GSS. The hallmark of the GSS
      neuropathology is the multi-centric plaque but the pattern varies between
      families. In the second part of this review the experimental data using
      experimental models of GSS in transgenic mice are summarised as well as
      structural biology of mutated PrP in GSS.

PMID- 16903148
TI  - Gerstmann-Straussler-Scheinker disease. II. An effect of GSS mutation on PRP
      structure.

PMID- 16903149
TI  - Ultrastructural alterations in the optic nerve in transmissible spongiform
      encephalopathies or prion diseases--a review.
AB  - The involvement of the visual system is well recognised in TSEs. The present
      review summarises the ultrastructural changes in the optic nerves in experimental
      infections of laboratory rodents with the agents of two human TSEs (CJD and GSS)
      and with two isolates of the scrapie agent. Vacuoles of myelinated fibres were
      found within myelin sheaths and themselves contained secondary vacuoles (vacuoles
      within other vacuoles) and curled membrane fragments not unlike the vacuoles in
      cerebral grey matter (see also: Spongiform change--an electron microscopic view;
      this issue). The myelin sheath had split either at the major dense line or at the
      intraperiod line. In addition, axons contained vacuoles within the axoplasm,
      corresponding to the typical spongiform vacuoles of grey matter. Vacuolation of
      myelinated fibres was accompanied by an exuberant cellular reaction consisting of
      macrophages containing numerous mitochondria, abundant rough endoplasmic
      reticulum and secondary lysosomes filled with digested myelin debris, electron
      dense material and sometimes entire myelin-bounded vacuoles. Within macrophages
      myelin fragments undergoing active digestion were often seen, together with lyre
      like bodies and paracrystalline inclusions. Astrocytes and their processes were
      prominent and glial filaments and many mitochondria were readily detected.
      Proliferation of the inner mesaxons was also seen. Cross-sectional profiles of
      many myelinated fibres contained membranous organelles continuous with the inner
      lamellae of the oligodendroglial cells. The inner mesaxon proliferations formed
      whorls and loops. In some axons proliferation was so severe that the mesaxonal
      loops filled the whole cross-section of the axon. Occasionally there was
      intrusion of the membranous tongue of the inner mesaxon into the axoplasm.
      Dystrophic neurites were relatively numerous. In GSS-infected animals some axons
      underwent demyelination with stripping of the myelin lamellae, while still others
      underwent vesicular myelin degeneration. It is of special note that in the
      cytoplasm of several cells as well as the axoplasm numerous autophagic vacuoles
      were seen.

PMID- 16903150
TI  - Echigo-1: a panencephalopathic strain of creutzfeldt-jakob disease. I.
      neuropathological and immunohistochemical studies.
AB  - We demonstrate an unusually intensive accumulation of prion protein (PrP) on
      neuronal membranes in hamsters infected with the Echigo-1 panencephalopathic
      strain of Creutzfeldt-Jakob disease. This stands in strong contrast with the poor
      vacuolation in this model. Several distinct patterns of PrP(TSE) deposit were
      observed in the brain. The first type consisted of a fine granular
      "synaptic"/diffuse type of accumulation which, especially in the cerebral cortex,
      appeared laminar. Deposits frequently coalesced to form plaque-like structures.
      The second pattern consisted of perivascular plaque-like accumulations. When a
      vessel was cut longitudinally, these formed long linear arrays of plaques and
      smaller globules. The third, and most striking, consisted of perineuronal
      deposits. These formed small dots and coarser globules which were densely
      situated on the neuronal membrane on both cell bodies and their processes.

PMID- 16903151
TI  - Echigo-1: a panencephalopathic strain of Creutzfeldt-Jakob disease. II.
      Ultrastructural studies in hamsters.
AB  - In this and a companion paper we present immunohistochemical and ultrastructural
      data on hamsters infected with the Echigo-1 strain of Creutzfeldt-Jakob disease.
      Ultrastructurally, two types of vacuoles were readily discriminated in the brain:
      the grey matter vacuoles of spongiform change and intramyelin vacuoles. The
      vacuoles were always membrane-bound; the membranes were single or double. The
      axons were entirely missing from the plane of the sections or, if visible, were
      shrunken and attached to the innermost layer of the myelin. It was noteworthy
      that some vacuoles indented cell bodies or processes and thus were reminiscent of
      the intraneuronal vacuoles typical for natural scrapie, BSE and CWD in ungulates
      and cervids but not of the vacuoles encountered in rodent models of scrapie and
      CJD. We also noticed vacuoles distending myelinated fibres in which the axons had
      become dystrophic. Some axons underwent Wallerian degeneration while others met
      the criteria for dystrophic neuritis. Both alterations existed in the same areas.
      Typical dystrophic neurites contained abnormal subcellular organelles, mainly
      electron-dense lysosomal inclusions. Other neurites contained numerous multi
      vesicular bodies and autophagic vacuoles. Nuclear paracrystalline rod-like
      inclusions were occasionally visible in neurons while other inclusions comprised
      spiroplasma-like inclusions in synaptic boutons. The robust cellular reactions
      consisted of reactive astrocytes and macrophages filled with cellular debris. It
      is of note that complex autophagic vacuoles were observed in the cytoplasm of
      neurons.

PMID- 16903152
TI  - Pediatric fractures of the foot and ankle.
AB  - Distal tibial physeal injuries are common in children, accounting for 10% to 40%
      of all injuries to skeletally immature patients. This article describes the
      classification, treatment, and complications of distal tibial fractures,
      fractures of the talus and calcaneus, midfoot and tarsometatarsal injuries,
      metatarsal fractures, and fractures of the phalanges in children.

PMID- 16903153
TI  - The management of lower extremity soft tissue and tendon trauma.
AB  - This article discusses the treatment of soft tissue injuries in the ankle and
      foot, including rupture of the Achilles tendon, Achilles tendonitis, peroneal
      tendonitis, peroneal tendon syndromes, and ankle sprain. It also discusses the
      causes, treatment, and reconstruction of soft tissue defects in the foot.

PMID- 16903154
TI  - Fractures of the forefoot.
AB  - Fractures of the forefoot are common injuries of various causes. Although not
      crippling, forefoot fractures can be debilitating if they go undiagnosed or are
      mistreated. Whenever patients complain of foot pain with ambulation or difficulty
      ambulating, radiographs should be taken as part of a standard routine to assess
      for bony pathology. This article discusses the classification and treatment of
      metatarsal fractures, digital and sesamoid fractures, and open fractures about
      the forefoot.

PMID- 16903155
TI  - Lisfranc fracture-dislocations: current treatment and new surgical approaches.
AB  - Anatomic reduction and restoration of the acute or chronic fracture-dislocation
      of the tarso-metatarsal joint is essential and needs to be addressed early in the
      patient's treatment with internal or external fixation. Long-term results
      following this injury can be associated with chronic instability, posttraumatic
      arthrosis, and poor functional outcomes. In this article, the authors review the
      current treatments of internal fixation and introduce new surgical techniques for
      addressing the acute or chronic tarso-metatarsal injuries with the application of
      circular multiplane external fixation devices.

PMID- 16903156
TI  - Midfoot fractures.
AB  - Fractures of the midfoot are uncommon because of the constrained configuration of
      multiple articular surfaces, which is augmented by capsular attachments and
      strong ligaments and tendons. Injury patterns usually involve more than one
      structure, although isolated fractures, dislocations, and sprains can occur. The
      key to optimal treatment of midfoot fractures is a high index of clinical
      suspicion because of their rareness. The traumatic midfoot injuries described in
      this article are categorized as Chopart joint injuries, tarsal scaphoid
      fractures, cuboid fractures, cuneiform fractures, and Lisfranc joint injuries.

PMID- 16903158
TI  - Treatment of late complications of intra-articular calcaneal fractures.
AB  - The unfortunately frequent complications of the articular fractures of the
      calcaneus have a high social impact, because of the frequent and long-lasting
      disability that they cause. This article discusses the treatment of the late
      complications of intra-articular calcaneal fractures.

PMID- 16903157
TI  - The use of Ilizarov technique and other types of external fixation for the
      treatment of intra-articular calcaneal fractures.
AB  - Treatment of severely comminuted calcaneal fractures with soft tissue compromise
      is still a controversial issue among surgeons. Complications of open reduction
      internal fixation have been well reported in the literature with a fairly high
      incidence of posttraumatic osteoarthritis of the subtalar joint, symptomatic
      hindfoot stiffness (especially when fixed in varus), wound dehiscence, and
      potential for the development of osteomyelitis caused by the extensive soft
      tissue trauma inherent with these injuries. For these reasons, closed treatment
      techniques using minimally invasive reduction procedures with application of ring
      type fine-wire external fixation have recently gained popularity.

PMID- 16903159
TI  - Ankle fractures.
AB  - Although ankle injuries are common, it is imperative for the treating physician
      to be able to identify the mechanism of injury and accurately restore the normal
      anatomy of the ankle joint. Attention must be given to restoring the normal
      alignment and length of the fibula because of its dominant role in controlling
      talar stability. The medial ankle must not be overlooked, with the role of the
      deltoid taken into consideration. With a thorough understanding of the anatomy,
      biomechanics, mechanism of injury, and fixation techniques, repair of the damaged
      ankle joint can lead to rewarding outcomes for the patient and physician.

PMID- 16903160
TI  - The surgical management of high- and low-energy tibial plafond fractures: A
      combination of internal and external fixation devices.
AB  - Fractures of the distal tibial articular surface are complex injuries that can
      destroy the ankle joint. This article discusses the mechanism of injury,
      classifications and historical means of treating these fractures, the authors'
      approach to treating low- and high-energy pilon fractures, prognosis, and
      complications.

PMID- 16903161
TI  - Current concepts in delayed bone union and non-union.
AB  - Healing of a fracture is a continuous process that involves various types of
      histologic regeneration at different sites. This article describes current
      approaches to managing delayed union and non-union of fracture.

PMID- 16903162
TI  - Current concepts and techniques in posttraumatic arthritis.
AB  - Posttraumatic arthrosis is a commonly encountered clinical problem, but the
      pathoetiology of its development is not yet clarified. Many contributing
      mechanical biologic factors interplay with the traumatic event that necessarily
      precedes the posttraumatic syndrome. New biologic concepts involving the ability
      of the cartilage to repair and how such healing can be promoted are being
      realized in new modalities of treatment. The traumatic event as such and the
      resulting pathomechanical consequences require new ways of evaluation.

PMID- 16903163
TI  - The management of acute Charcot fracture-dislocations with the Taylor's spatial
      external fixation system.
AB  - The surgical repair of acute diabetic neuropathic osteoarthropathy of the midfoot
      remains a challenge with little guidance available in the medical literature. The
      authors present a review of the diabetic Charcot neuropathic osteoarthropathy
      process and proposed surgical intervention techniques with a special emphasis on
      the available data regarding the use of external fixation. A detailed, step-by
      step, guide through the foot-specific Taylor spatial external fixation system is
      provided. Finally, the authors' preferred technique for these difficult limb
      salvage cases is presented in detail.

PMID- 16903164
TI  - Managing cardiovascular risk in patients with metabolic syndrome.
AB  - Metabolic syndrome consists of a cluster of cardiovascular (CV) and metabolic
      risk factors (e.g., abdominal obesity, hypertension, elevated levels of fasting
      plasma glucose and triglycerides, and low levels of high-density lipoprotein
      cholesterol [HDL-C]) and is associated with an increased risk for type 2 diabetes
      mellitus (DM) and cardiovascular disease (CVD). Because the risks for CVD and
      type 2 DM are highly variable among patients with metabolic syndrome, it is
      essential to assess a patient's risks before identifying specific treatment or
      lifestyle interventions. The major risk factors for CVD are smoking,
      hypertension, elevated levels of total and low-density lipoprotein cholesterol,
      low levels of HDL-C, and older age. In patients at low risk for CV events,
      lifestyle interventions (i.e., weight loss and increased physical activity) may
      be sufficient to control the components of metabolic syndrome and to reduce the
      risk for type 2 DM and CVD. Patients who are at high risk, however, must receive
      aggressive drug therapy in addition to lifestyle interventions. The following
      factors need to be targeted: obesity (particularly abdominal obesity),
      dyslipidemia, hypertension, and prothrombotic/proinflammatory states. Drugs with
      various and complementary mechanisms of action, including drugs targeting lipid
      metabolism, may be effective in controlling these factors and thereby delaying or
      preventing CV events and type 2 DM.

PMID- 16903165
TI  - Successful control of dyslipidemia in patients with metabolic syndrome: focus on
      lifestyle changes.
AB  - Approaches to controlling dyslipidemia in patients with metabolic syndrome must
      take into consideration a patient's individual characteristics and underlying
      lipid disorder. Some patients will require pharmacologic therapy, whereas others
      can be controlled with lifestyle changes alone. The National Cholesterol
      Education Program (NCEP) Adult Treatment Panel III (ATP III) guidelines recommend
      that patients with at least 3 of the following clinical variables be designated
      as having metabolic syndrome: abdominal obesity as reflected in increased waist
      circumference; a low high-density lipoprotein cholesterol (HDL-C) level; an
      elevated triglyceride level; elevated blood pressure or treatment with
      antihypertensive medications; and/or elevated fasting plasma glucose or treatment
      with antidiabetic medications. Unless patients with metabolic syndrome change
      their lifestyle, existing cardiovascular and metabolic risk factors will worsen
      or new risk factors will develop. This helps explain why these patients are at
      increased risk for developing type 2 diabetes mellitus (DM) and coronary heart
      disease (CHD). The lifestyle changes recommended by NCEP ATP III for controlling
      dyslipidemia (i.e., elevated levels of triglycerides and decreased levels of HDL
      C) in patients with metabolic syndrome or type 2 DM include (1) reduced intake of
      saturated fats and dietary cholesterol, (2) intake of dietary options to enhance
      lowering of low-density lipoprotein cholesterol, (3) weight control, and (4)
      increased physical activity. If lifestyle changes are not successful for
      individuals at high risk of developing CHD, or for those who currently have CHD,
      a CHD risk equivalent, or persistent atherogenic dyslipidemia, then
      pharmacotherapy may be necessary as defined by NCEP ATP III guidelines.

PMID- 16903166
TI  - Atherogenic dyslipidemia associated with metabolic syndrome and insulin
      resistance.
AB  - Atherogenic dyslipidemia, a component of metabolic syndrome, is characterized by
      high levels of apolipoprotein B (apo B)-containing lipoproteins, including very
      low-density lipoprotein remnants and small low-density lipoprotein particles, and
      reduced levels of high-density lipoprotein cholesterol. Although the National
      Cholesterol Education Program Adult Treatment Panel III includes elevations in
      blood pressure and plasma glucose in the definition of metabolic syndrome, the
      broader scope of metabolic syndrome includes proinflammatory and prothrombotic
      states, which derive from the secretory activity of adipose tissue. Abdominal fat
      can adversely affect insulin action and the disposal of glucose through an
      increase in the release of free fatty acid, resulting in accumulation of
      triglyceride in muscle and liver, thereby depressing insulin action and
      increasing output of apo B-containing lipoproteins. Impaired regulation of
      adipokines, bioactive substances secreted from adipose tissue, likely produces
      systemic inflammation, which can promote atherogenesis. Insulin resistance is
      recognized as an important metabolic defect linking the components of metabolic
      syndrome. One molecule that may play an important role in metabolic syndrome to
      regulate metabolic and vascular pathways is the peroxisome proliferator-activated
      receptor-gamma (PPAR-gamma). Studies have established PPAR-gamma deficiency as a
      cause of lipodystrophy and confirmed its adipogenic role. Patients with
      atherogenic dyslipidemia and metabolic syndrome should undergo global risk
      assessment for cardiovascular disease and future cardiovascular events to
      determine an overall treatment strategy.

PMID- 16903167
TI  - Step up to the cancer gold standard.

PMID- 16903168
TI  - Industrial accidents.

PMID- 16903169
TI  - Tailor made for safety.

PMID- 16903170
TI  - Indoor air concerns.

PMID- 16903171
TI  - Remember the training component.

PMID- 16903172
TI  - Developing performance based goals and outcomes.

PMID- 16903173
TI  - The do's & don'ts of first aid compliance.

PMID- 16903174
TI  - West Nile virology.

PMID- 16903175
TI  - Puncture-resistant footwear: arch nemesis of the rusty nail.

PMID- 16903176
TI  - Carbon dioxide measures up as a real hazard.

PMID- 16903177
TI  - Five-gas comes of age.
AB  - PIDs and a range of electrochemical sensors have become commonplace as extra
      sensors in conventional 4-gas confined space entry meters to protect workers from
      exposure to a broad array of toxic organic and inorganic vapors. New wireless
      transmission systems have opened up a host of safer and faster detection
      capabilities, requiring less operator involvement and thus saving costs.

PMID- 16903178
TI  - The five W's of hazmat decontamination.

PMID- 16903179
TI  - Using the web to simplify compliance.

PMID- 16903180
TI  - Online and on time.

PMID- 16903181
TI  - Making hospital triage operations safer.

PMID- 16903182
TI  - How to choose the right escape mask.

PMID- 16903183
TI  - OSHA's multi-employer work site policy: who's on first?

PMID- 16903184
TI  - Hanging on a line.

PMID- 16903185
TI  - HazDat in action.

PMID- 16903186
TI  - Get your program in top shape.

PMID- 16903187
TI  - Helping children play.

PMID- 16903188
TI  - Why girls will be girls.

PMID- 16903189
TI  - Cavemen, chimps and us. What can we learn from Neanderthal genes?

PMID- 16903190
TI  - What the doctor did. In Katrina's wake, a deadly hospital mystery unfolds.

PMID- 16903191
TI  - A platinum standard of effectiveness in oral health care interventions: the
      Cochrane systematic review.

PMID- 16903192
TI  - FDA new drug approvals in 2005.

PMID- 16903193
TI  - Dentist-patient-laboratory communication: part II.

PMID- 16903194
TI  - What your physician doesn't tell you about cholesterol.

PMID- 16903195
TI  - Resin-based sealing of root canals in endodontic therapy.
AB  - This study evaluated the effect of the obturation technique on leakage, which may
      be the primary cause of failure in endodontic treatment. The apical seal and
      leakage behavior of teeth obturated with a resin-based sealer and gutta-percha
      alternative were compared to conventionally obturated teeth. Sound premolars (N =
      10) were instrumented and treated by conventional root canal obturation. A second
      group (N = 10) was treated with the Resilon-Epiphany system and the remaining 10
      roots were divided into two groups (N = 5) and obturated without sealer. A
      detector electrode was placed coronally in each root in contact with the
      obturation system and sealed in place and the apices were left patent. The teeth
      were immersed in 0.9% sodium chloride with a stainless steel counter electrode. A
      20V potential was connected between the stainless steel and each tooth in turn
      with current flow determined by voltage drop across a standard resistor. Leakage
      was followed for 30 days and statistically analyzed for differences between
      groups. All teeth in Groups 1, 3A, and 38 (p > 0.05) leaked at 30 days. In Group
      2, four roots showed no leakage, five roots showed minimal leakage, and one root
      exhibited a leakage current at a greater magnitude than the others in the group.
      A significant difference (p < 0.005) was found between Groups 1 and 2 but not
      between Group 1 and Groups 3A and 3B (p > 0.05) or between Group 2 and Groups 3A
      and 3B.

PMID- 16903196
TI  - A review of sodium fluoride varnish.
AB  - Fluoride varnish was incorporated into clinical dentistry to reduce caries; its
      use in the U.S. has increased progressively since it was approved by the FDA in
      1994. This paper reviewed clinical studies and found that fluoride varnish's
      effectiveness in caries prevention, ease of application, and safety give it an
      advantage over other types of topical fluoride treatments (such as gels and
      rinses) or other caries management methods. As a result, it is regarded as one of
      the superior topical fluoride agents for young children.

PMID- 16903197
TI  - Comparing cutting efficiencies of diamond burs using a high-speed electric
      handpiece.
AB  - This study sought to compare the cutting efficiency of different diamond burs on
      initial use as well as during repeated use, alternating with sterilization. Long,
      round-end, tapered diamond burs with similar diameter, profile, and diamond
      coarseness (125-150 microm grit) were used. A high-torque, high-speed electric
      handpiece (set at 200,000 rpm) was utilized with a coolant flow rate of 25
      mL/min. Burs were tested under a constant load of 170 g while cuts were made on a
      machinable ceramic substrate block. Each bur was subjected to five consecutive
      cuts for 30 seconds of continuous operation and the cutting depths were measured.
      All burs performed similarly on the first cut. Cutting efficiencies for three of
      the bur groups decreased significantly after the first cycle; however, by the
      fifth cycle, all bur groups performed similarly without any significant
      differences (p > 0.05). A scanning electron microscope revealed significant
      crystal loss after each use.

PMID- 16903198
TI  - Clinical and radiographic evaluation of pulpotomies employing calcium hydroxide
      and trioxide mineral aggregate.
AB  - This study utilized clinical and radiographic examinations to compare the
      effectiveness of calcium hydroxide paste and mineral trioxide aggregate (MTA) for
      pulpotomies of primary molars in children. Ninety primary molars that showed
      clinical and radiographic indications for pulpotomy treatment were selected. The
      pulpotomies were performed in two sessions, using a corticosteroid/antibiotic
      solution as therapeutic dressing. The sample was divided into two groups of 45
      teeth, in which the pulpal remains were protected with either calcium hydroxide
      paste (Group 1) or MTA (Group 2). Radiographs were taken immediately and at 3-, 6
      , and 12-month follow-up appointments. Three teeth in Group 1 failed after three
      months, while two cases failed after six months and one more failed at one year.
      Two failures were found in Group 2 at the 12-month follow-up. These results
      indicate that both materials may be utilized for pulpotomies in primary teeth.

PMID- 16903199
TI  - Pemphigus vulgaris in a juvenile patient: case report.
AB  - Pemphigus vulgaris is a rare cause of oral mucosal ulceration that mainly affects
      middle-aged adults; the oral lesions of pemphigus are associated with cutaneous
      manifestations. This article reports a case of oral phemphigus vulgaris in a 17
      year-old girl without any cutaneous lesions. After seven months of steroid
      therapy, the disease was controlled. Early recognition of this disease may
      prevent delayed diagnosis and incorrect treatment.

PMID- 16903200
TI  - Endodontic treatment of a maxillary central incisor with two separate roots: case
      report.
AB  - This case report involves endodontic treatment of a traumatized maxillary central
      incisor with two separate roots. Although the literature has reported that
      maxillary central incisors always have one root with one canal, this report
      (among others) serves to remind dentists that occasional morphological variations
      exist and should be ruled out when this type of tooth is treated.

PMID- 16903201
TI  - A retrospective evaluation of 56 patients with oral burning and limited clinical
      findings.
AB  - This study retrospectively evaluated the charts of 56 patients who had been
      referred to an oral medicine clinic between 1995 and 2004 with oral burning and
      limited clinical findings. Of the 56 patients, 35 had a final diagnosis of
      essential burning mouth disorder (EBMD). Five patients with EBMD had a family
      history of diabetes and two had been diagnosed with late-onset diabetes. Other
      oral burning diagnoses included sialoadenitis (burning lips syndrome), irritation
      or allergic reactions to triclosan, diabetic neuropathy, subclinical oral
      candidiasis, nutritional deficiency/neuropathy, and a drug reaction to an ACE
      inhibitor (scalded mouth syndrome) that resulted in oral burning.

PMID- 16903202
TI  - The patient with actinic cheilosis.
AB  - Recent research has greatly enhanced the understanding of the etiopathogenic
      pathways underlying squamous cell carcinoma (SCC) of the skin. The predominant
      etiologic agent is ultraviolet radiation. Excessive exposure to sunlight may lead
      to the development of sunburn, premature aging of the skin, cataracts, immune
      suppression, and skin cancer. Actinic keratoses represent an early clinical stage
      of a continuum that ultimately may progress to become SCC of the skin. Actinic
      cheiloses represent actinic keratoses that occur on the lip vermilion. While
      numerous therapeutic measures are available for managing actinic cheilosis, close
      follow-up, combined with strict measures to reduce future sun exposure, is
      mandatory. Oral health care providers are in a prime position to identify
      patients at risk for actinic cheiloses, educate patients on preventive measures
      to reduce and negate the damaging effects of sunlight, and (if necessary) manage
      early actinic cheiloses.

PMID- 16903203
TI  - Oral lesions commonly associated with pediatric HIV infection--presentation,
      management, and review of the literature.
AB  - At the end of 2004, the United Nations HIV/AIDS program estimated that 2.5
      million children worldwide under the age of 15 were living with HIV/AIDS, while
      approximately 500,000 children under 15 had died from disease-related cases in
      that year alone. In the U.S., 90% of infected children acquire the disease
      perinatally from a mother with a known risk for infection. HIV-associated
      conditions in children are quite different from those in adults in type,
      severity, and progression. This article focuses on oral lesions found commonly
      among pediatric HIV patients.

PMID- 16903204
TI  - Nodular swelling of anterior buccal mucosa.

PMID- 16903205
TI  - Extensive palatal erosion.

PMID- 16903206
TI  - G1 phase: components, conundrums, context.
AB  - A eukaryotic cell must coordinate DNA synthesis and chromosomal segregation to
      generate a faithful replica of itself. These events are confined to discrete
      periods designated synthesis (S) and mitosis (M), and are separated by two gap
      periods (Gl and G2). A complete proliferative cycle entails sequential and
      regulated progression through G1, S, G2, and M phases. During G1, cells receive
      information from the extracellular environment and determine whether to
      proliferate or to adopt an alternate fate. Work in yeast and cultured mammalian
      cells has implicated cyclin dependent kinases (Cdks) and their cyclin regulatory
      partners as key components controlling G1. Unique cyclin/Cdk complexes are
      temporally expressed in response to extracellular signaling, whereupon they
      phosphorylate specific targets to promote ordered G1 progression and S phase
      entry. Cyclins and Cdks are thought to be required and rate-limiting for cell
      proliferation because manipulating their activity in yeast and cultured mammalian
      cells alters G1 progression. However, recent evidence suggests that these same
      components are not necessarily required in developing mouse embryos or cells
      derived from them. The implications of these intriguing observations for
      understanding G1 progression and its regulation are discussed.

PMID- 16903207
TI  - Regulation of S phase.
AB  - Regulation of DNA replication is critical for accurate and timely dissemination
      of genomic material to daughter cells. The cell uses a variety of mechanisms to
      control this aspect of the cell cycle. There are various determinants of origin
      identification, as well as a large number of proteins required to load
      replication complexes at these defined genomic regions. A pre-Replication Complex
      (pre-RC) associates with origins in the G1 phase. This complex includes the
      Origin Recognition Complex (ORC), which serves to recognize origins, the putative
      helicase MCM2-7, and other factors important for complex assembly. Following pre
      RC loading, a pre-Initiation Complex (pre-IC) builds upon the helicase with
      factors required for eventual loading of replicative polymerases. The chromatin
      association of these two complexes is temporally distinct, with pre-RC being
      inhibited, and pre-IC being activated by cyclin-dependent kinases (Cdks). This
      regulation is the basis for replication licensing, which allows replication to
      occur at a specific time once, and only once, per cell cycle. By preventing extra
      rounds of replication within a cell cycle, or by ensuring the cell cycle cannot
      progress until the environmental and intracellular conditions are most optimal,
      cells are able to carry out a successful replication cycle with minimal
      mutations.

PMID- 16903208
TI  - Checkpoint and coordinated cellular responses to DNA damage.
AB  - The DNA damage and replication checkpoints are signaling mechanisms that regulate
      and coordinate cellular responses to genotoxic conditions. The activation of
      checkpoints not only attenuates cell cycle progression, but also facilitates DNA
      repair and recovery of faulty replication forks, thereby preventing DNA lesions
      from being converted to inheritable mutations. It has become increasingly clear
      that the activation and signaling of the checkpoint are intimately linked to the
      cellular processes directly involved in chromosomal metabolism, such as DNA
      replication and DNA repair. Thus, the checkpoint pathway is not just a
      surveillance system that monitors genomic integrity and regulates cell
      proliferation, but also an integral part of the processes that work directly on
      chromosomes to maintain genomic stability. In this article, we discuss the
      current models of DNA damage and replication checkpoints, and highlight recent
      advances in the field.

PMID- 16903209
TI  - Protein kinases involved in mitotic spindle checkpoint regulation.
AB  - A number of checkpoint controls function to preserve the genome by restraining
      cell cycle progression until prerequisite events have been properly completed.
      Chromosome attachment to the mitotic spindle is monitored by the spindle assembly
      checkpoint. Sister chromatid separation in anaphase is initiated only once all
      chromosomes have been attached to both poles of the spindle. Premature separation
      of sister chromatids leads to the loss or gain of chromosomes in daughter cells
      (aneuploidy), a prevalent form of genetic instability of human cancer. The
      spindle assembly checkpoint ensures that cells with misaligned chromosomes do not
      exit mitosis and divide to form aneuploid cells. A number of protein kinases and
      checkpoint phosphoproteins are required for the function of the spindle assembly
      checkpoint. This review discusses the recent progress in understanding the role
      of protein kinases of the mitotic checkpoint complex in the surveillance pathway
      of the checkpoint.

PMID- 16903210
TI  - The centrosome cycle.
AB  - Centrosomes are dynamic organelles involved in many aspects of cell function and
      growth. Centrosomes act as microtubule organizing centers, and provide a site for
      concerted regulation of cell cycle progression. While there is diversity in
      microtubule organizing center structure among eukaryotes, many centrosome
      components, such as centrin, are conserved. Experimental analysis has provided an
      outline to describe centrosome duplication, and numerous centrosome components
      have been identified. Even so, more work is needed to provide a detailed
      understanding of the interactions between centrosome components and their roles
      in centrosome function and duplication. Precise duplication of centrosomes once
      during each cell cycle ensures proper mitotic spindle formation and chromosome
      segregation. Defects in centrosome duplication or function are linked to human
      diseases including cancer. Here we provide a multifaceted look at centrosomes
      with a detailed summary of the centrosome cycle.

PMID- 16903211
TI  - The ubiquitin-proteasome pathway in cell cycle control.
AB  - Ubiquitin-mediated proteolysis is one of the key mechanisms underlying cell cycle
      control. The removal of barriers posed by accumulation of negative regulators, as
      well as the clearance of proteins when they are no longer needed or deleterious,
      are carried out via the ubiquitin-proteasome system. Ubiquitin conjugating
      enzymes and protein-ubiquitin ligases collaborate to mark proteins destined for
      degradation by the proteasome by covalent attachment of multi-ubiquitin chains.
      Most regulated proteolysis during the cell cycle can be attributed to two
      families of protein-ubiquitin ligases. The anaphase promoting complex/cyclosome
      (APC/C) is activated during mitosis and G1 where it is responsible for
      eliminating proteins that impede mitotic progression and that would have
      deleterious consequences if allowed to accumulate during G1. SCF (Skp1/Culin/F
      box protein) protein-ubiquitin ligases ubiquitylate proteins that are marked by
      phosphorylation at specific sequences known as phosphodegrons. Targeting of
      proteins for destruction by phosphorylation provides a mechanism for linking cell
      cycle regulation to internal and external signaling pathways via regulated
      protein kinase activities.

PMID- 16903212
TI  - The retinoblastoma gene family in cell cycle regulation and suppression of
      tumorigenesis.
AB  - Since its discovery in 1986, as the first tumor suppressor gene, the
      retinoblastoma gene (Rb) has been extensively studied. Numerous biochemical and
      genetic studies have elucidated in great detail the function of the Rb gene and
      placed it at the heart of the molecular machinery controlling the cell cycle. As
      more insight was gained into the genetic events required for oncogenic
      transformation, it became clear that the retinoblastoma gene is connected to
      biochemical pathways that are dysfunctional in virtually all tumor types. Besides
      regulating the E2F transcription factors, pRb is involved in numerous biological
      processes such as apoptosis, DNA repair, chromatin modification, and
      differentiation. Further complexity was added to the system with the discovery of
      p107 and p130, two close homologs of Rb. Although the three family members share
      similar functions, it is becoming clear that these proteins also have unique
      functions in differentiation and regulation of transcription. In contrast to Rb,
      p107 and p130 are rarely found inactivated in human tumors. Yet, evidence is
      accumulating that these proteins are part of a "tumor-surveillance" mechanism and
      can suppress tumorigenesis. Here we provide an overview of the knowledge obtained
      from studies involving the retinoblastoma gene family with particular focus on
      its role in suppressing tumorigenesis.

PMID- 16903213
TI  - Modeling cell cycle control and cancer with pRB tumor suppressor.
AB  - Cancer is a complex syndrome of diseases characterized by the increased abundance
      of cells that disrupts the normal tissue architecture within an organism.
      Defining one universal mechanism underlying cancer with the hope of designing a
      magic bullet against cancer is impossible, largely because there is so much
      variation between various types of cancer and different individuals. However, we
      have learned much in past decades about different journeys that a normal cell
      takes to become cancerous, and that the delicate balance between oncogenes and
      tumor suppressor is upset, favoring growth and survival of the tumor cell. One of
      the most important cellular barriers to cancer development is the retinoblastoma
      tumor suppressor (pRB) pathway, which is inactivated in a wide range of human
      tumors and controls cell cycle progression via repression of the E2F/DP
      transcription factor family. Much of the clarity with which we view tumor
      suppression via pRB is due to our belief in the universality of the cell cycle
      and our attempts to model tumor pathways in vivo, nowhere so evident as in the
      multitude of data emerging from mutant mouse models that have been engineered to
      understand how cell cycle regulators limit growth in vivo and how deregulation of
      these regulators facilitates cancer development. In spite of this clarity, we
      have witnessed with incredulity several stunning results in the last 2 years that
      have challenged the very foundations of the cell cycle paradigm and made us
      question seriously how important these cell cycle regulators actually are.

PMID- 16903214
TI  - Senescence and cell cycle control.
AB  - In response to various stresses, such as telomere shortening during continuous
      proliferation, oxidative stress, DNA damage and aberrant oncogene activation,
      normal cells undergo cellular senescence, which is a stable postmitotic state
      with particular morphology and metabolism. Signaling that induces senescence
      involves two major tumor suppressor cascades, i.e., the INK4a-Rb pathway and the
      ARF-p53 pathway. Diverse stimuli upregulate these interacting pathways, which
      orchestrate exit from the cell cycle. Recent studies have provided insights into
      substantial differences in senescence-inducing signals in primary cells of human
      and rodent origins. This review is focused on recent advances in understanding
      the roles of the tumor-suppressive pathways in senescence.

PMID- 16903215
TI  - Mouse models of cell cycle regulators: new paradigms.
AB  - In yeast, a single cyclin-dependent kinase (Cdk) is able to regulate diverse cell
      cycle transitions (S and M phases) by associating with multiple stage-specific
      cyclins. The evolution of multicellular organisms brought additional layers of
      cell cycle regulation in the form of numerous Cdks, cyclins and Cdk inhibitors to
      reflect the higher levels of organismal complexity. Our current knowledge about
      the mammalian cell cycle emerged from early experiments using human and rodent
      cell lines, from which we built the current textbook model of cell cycle
      regulation. In this model, the functions of different cyclin/Cdk complexes were
      thought to be specific for each cell cycle phase. In the last decade, studies
      using genetically engineered mice in which cell cycle regulators were targeted
      revealed many surprises. We discovered the in vivo functions of cell cycle
      proteins within the context of a living animal and whether they are essential for
      animal development. In this review, we discuss first the textbook model of cell
      cycle regulation, followed by a global overview of data obtained from different
      mouse models. We describe the similarities and differences between the phenotypes
      of different mouse models including embryonic lethality, sterility,
      hematopoietic, pancreatic, and placental defects. We also describe the role of
      key cell cycle regulators in the development of tumors in mice, and the
      implications of these data for human cancer. Furthermore, animal models in which
      two or more genes are ablated revealed which cell cycle regulators interact
      genetically and functionally complement each other. We discuss for example the
      interaction of cyclin D1 and p27 and the compensation of Cdk2 by Cdc2. We also
      focus on new functions discovered for certain cell cycle regulators such as the
      regulation of S phase by Cdc2 and the role of p27 in regulating cell migration.
      Finally, we conclude the chapter by discussing the limitations of animal models
      and to what extent can the recent findings be reconciled with the past work to
      come up with a new model for cell cycle regulation with high levels of redundancy
      among the molecular players.

PMID- 16903216
TI  - Control of cell proliferation and growth by Myc proteins.
AB  - Myc proteins act as signal transducers that alter cell proliferation in
      dependence on signals from the extracellular environment. In normal cells, the
      expression of MYC genes is therefore under tight control by growth factor
      dependent signals. The enormous interest in the function of these proteins is
      motivated by the observation that the close control of MYC expression is
      disrupted in a large percentage of human tumors, leading to deregulated
      expression of Myc proteins. A large body of evidence shows that this deregulation
      is a major driving force of human tumorigenesis; in cells with deregulated Myc,
      proliferation often takes place in the complete absence of external stimuli. We
      will discuss current models to understand Myc function and also potential avenues
      to selectively interfere with the proliferation of Myc-transformed cells.

PMID- 16903217
TI  - Cell cycle regulation in mammalian germ cells.
AB  - Meiosis is a unique form of cellular division by which a diploid cell produces
      genetically distinct haploid gametes. Initiation and regulation of mammalian
      meiosis differs between the sexes. In females, meiosis is initiated during embryo
      development and arrested shortly after birth during prophase I. In males,
      spermatogonial stem cells initiate meiosis at puberty and proceed through
      gametogenesis with no cell cycle arrest. Mouse genes required for early meiotic
      cell cycle events are being identified by comparative analysis with other
      eukaryotic systems, by virtue of gene knockout technology and by mouse
      mutagenesis screens for reproductive defects. This review focuses on mouse
      reproductive biology and describes the available mouse mutants with defects in
      the early meiotic cell cycle and prophase I regulatory events. These research
      tools will permit rapid advances in such medically relevant research areas as
      infertility, embryo lethality and developmental abnormalities.

PMID- 16903218
TI  - Structure and replication of hepatitis delta virus RNA.
AB  - While this volume covers many different aspects of hepatitis delta virus (HDV)
      replication, the focus in this chapter is on studies of the structure and
      replication of the HDV RNA genome. An evaluation of such studies is not only an
      integral part of our understanding of HDV infections but it also sheds new light
      on some important aspects of cell biology, such as the fidelity of RNA
      transcription by a host RNA polymerase and on various forms of post
      transcriptional RNA processing. Representations of the replication of the RNA
      genome are frequently simplified to a form of rolling-circle model, analogous to
      what have been described for plant viroids. One theme of this review is that such
      models, even after some revision, deceptively simplify the complexity of HDV
      replication and can fail to make clear major questions yet to be solved.

PMID- 16903219
TI  - HDV RNA replication: ancient relic or primer?
AB  - HDV replicates its circular RNA genome using a double rolling-circle mechanism
      and transcribes a hepatitis delta antigen-encodeing mRNA from the same RNA
      template during its life cycle. Both processes are carried out by RNA-dependent
      RNA synthesis despite the fact that HDV does not encode an RNA-dependent RNA
      polymerase (RdRP). Cellular RNA polymerase II has long been implicated in these
      processes. Recent findings, however, have shown that the syntheses of genomic and
      antigenomic RNA strands have different metabolic requirements, including
      sensitives to alpha-amanitin and the site of synthesis. Evidence is summarized
      here for the involvement of other cellular polymerases, probably pol I, in the
      synthesis of antigenomic RNA strand. The ability of mammalian cells to replicate
      HDV RNA implies that RNA-dependent RNA synthesis was preserved throughout
      evolution.

PMID- 16903220
TI  - HDV ribozymes.
AB  - The self-cleaving RNA sequences, or ribozymes, in the genomic and antigenomic
      strands of hepatitis delta virus (HDV) RNA fold into structures that are similar
      to each other but distinct from those of small ribozymes associated with the RNA
      replicons that infect plants. HDV ribozymes have provided a tractable system for
      studying the mechanism of catalytic RNA, and results of biochemical and
      structural studies on the HDV ribozymes, from a number of labs, have enhanced our
      understanding and expanded our thinking about the potential for catalytic roles
      of RNA side chains. The results of these studies are consistent with models
      suggesting that both an active-site cytosine and a divalent metal ion have
      catalytic roles in facilitating the cleavage reaction in the HDV ribozymes.
      Despite recent advances, details about the catalytic mechanism of the HDV
      ribozyme continue to be debated, and these ribozymes should serve as a good
      system for further study.

PMID- 16903221
TI  - RNA editing in hepatitis delta virus.
AB  - Hepatitis delta virus (HDV) relies heavily on host functions and on structural
      features of the viral RNA. A good example of this reliance is found in the
      process known as HDV RNA editing, which requires particular structural features
      in the HDV antigenome, and a host RNA editing enzyme, ADAR1. During replication,
      the adenosine at the amber/W site in the HDV antigenome is edited to inosine. As
      a result, the amber stop codon in the hepatitis delta antigen (HDAg) open reading
      frame is changed to a tryptophan codon and the reading frame is extended by 19 or
      20 codons. Because these extra amino acids alter the functional properties of
      HDAg, this change serves a critical purpose in the HDV replication cycle.
      Analysis of the RNA secondary structures and regulation of editing in HDV
      genotypes I and III has indicated that although editing is essential for both
      genotypes, there are substantial differences. This review covers the mechanisms
      of RNA editing in the HDV replication cycle and the regulatory mechanisms by
      which HDV controls editing.

PMID- 16903222
TI  - Post-translational modification of delta antigen of hepatitis D virus.
AB  - The hepatitis delta virus (HDV) genome has only one open reading frame, which
      encodes the viral small delta antigen. After RNA editing, the same open reading
      frame is extended 19 amino acids at the carboxyl terminus and encodes the large
      delta antigen. These two viral proteins escort the HDV genome through different
      cellular compartments for the complicated phases of replication, transcription
      and, eventually, the formation of progeny virions. To orchestrate these events,
      the delta antigens have to take distinct cues to traffic to the right
      compartments and make correct molecular contacts. In eukaryotes, post
      translational modification (PTM) is a major mechanism of dictating the multiple
      functions of a single protein. Multiple PTMs, including phosphorylation,
      isoprenylation, acetylation, and methylation, have been identified on hepatitis
      delta antigens. In this chapter we review these PTMs and discuss their functions
      in regulating and coordinating the life cycle of HDV.

PMID- 16903223
TI  - The role of the HBV envelope proteins in the HDV replication cycle.
AB  - The hepatitis delta virus (HDV) is a subviral agent that utilizes the envelope
      proteins of the hepatitis B virus (HBV) for propagation. When introduced into
      permissive cells, the HDV RNA genome replicates and associates with multiple
      copies of the HDV-encoded proteins to assemble a ribonucleoprotein (RNP) complex.
      The mechanism necessary to export the RNP from the cell is provided by the HBV
      envelope proteins, which have the capacity to assemble lipoprotein vesicles that
      bud into the lumen of a pre-Golgi compartment before being secreted. In addition
      to allowing the release of the HDV RNP, the HBV envelope proteins also provide a
      means for its targeting to an uninfected cell, thereby ensuring the spread of
      HDV. This chapter covers the molecular aspects of the HBV envelope protein
      functions in the HDV replication cycle, in particular the activity of the small
      envelope protein in RNP export and the function of the large envelope protein at
      viral entry.

PMID- 16903224
TI  - Prenylation of HDAg and antiviral drug development.
AB  - Hepatitis delta virus (HDV) is an important cause of acute and chronic liver
      disease. Current medical therapies are unable to effectively eradicate HDV
      infections. Research into the molecular virology of the HDV life cycle has
      revealed a fascinating collection of biology. These insights are now beginning to
      be translated into new potential treatment strategies. For example, an essential
      step in the virus assembly process involves the post-translational lipid
      modification of a specific HDV protein, namely prenylation of large delta
      antigen. Preventing prenylation abolishes virus particle formation. Drugs capable
      of specifically inhibiting prenylation have been developed for use in humans.
      These agents represent a new class of antiviral agents, with HDV as a first
      target. Here, a brief review of the HDV life cycle emphasizing the role of
      prenylation is presented along with implications for drug development and
      therapy.

PMID- 16903225
TI  - Hepatitis delta virus genetic variability: from genotypes I, II, III to eight
      major clades?
AB  - Hepatitis D virus (HDV) is a satellite of hepatitis B virus (HBV) for
      transmission and propagation, and infects nearly 20 million people worldwide. The
      HDV genome is composed of a compact circular single-stranded negative RNA genome
      with extensive intramolecular complementarity. Along with epidemiological,
      geographic distribution and pathological patterns, the variability of HDV has
      been limited to three genotypes and two subtypes that have been characterized to
      date. Recently, extensive phylogenetic reconstructions based on the delta antigen
      gene and full-length genome sequence data, have shown a wide and probably ancient
      radiation of African lineages, suggesting that the genetic variability of HDV is
      much more complex than previously thought. Indeed, sequences previously
      affiliated with genotype IIb should now be considered as belonging to clade 4
      (HDV-4) and African HDV sequences segregate within four additional clades: HDV-5,
      HDV-6, HDV-7 and HDV-8. These results bring the geographic distribution of HDV
      closer to the genetic variability of its helper HBV.

PMID- 16903226
TI  - Functional and clinical significance of hepatitis D virus genotype II infection.
AB  - Hepatitis D virus (HDV) infection is one of the important etiologies of fulminant
      hepatitis and may aggravate the clinical course of chronic HBV infection to
      cirrhosis and liver failure. HDV was classified into three genotypes. Recent
      molecular phylogenetic analysis of HDV suggests at least seven major clades. The
      genotype I HDV is widely spread, genotype II is found in East Asia and genotype
      III HDV is prevalent in South America. The genomic size is 1682-1685 nucleotides
      (nt) for genotype II, and 1676 nt for genotype IV (IIb). The divergence in HDV
      nucleic acid sequences between genotype II and other genotypes varies from 13.8%
      to 35.3%. The divergences in the HDAg-coding region may range from 17.8% to 29.8%
      between genotype II and other genotypes. There is no genotypic or size
      restriction on the interactions of either the small or the large hepatitis delta
      antigens (HDAgs) between genotypes I and II, and there is also no genotypic
      incompatibility during co-package of HDAgs of different genotypes into virus like
      particles. There appears no apparent universal genotypic restriction of the
      transactivation of genotype I HDV RNA replication by small HDAg of genotype II.
      In contrast, there appears more genotypic restriction for genotype I small HDAgs
      to transactivate genotype II HDV RNA replication. Of the functional domains of
      HDAg, the 19 amino acids at the carboxyl-end of the large HDAg show the greatest
      divergences (70%-80%) between genotypes I and II. The viral packaging
      efficiencies of genotype I HDV isolates are usually higher than those of genotype
      II. The 19 amino acids at the carboxyl-end seem to be the most important
      determinant for viral packaging efficiencies. The editing efficiencies of the
      genotype I HDV are also higher than those of the genotype II. Genotype II HDV
      infection is relatively less frequently associated with fulminant hepatitis at
      the acute stage and less unfavorable outcomes [cirrhosis or hepatocellular
      carcinoma (HCC)] at the chronic stage as compared to genotype I. It appears that
      the clinical manifestations and outcomes of patients with genotype IV (IIb) HDV
      infection are more like those of patients with genotype II HDV infection.
      Persistent replication of HBV or HDV was associated with higher adverse outcomes
      (cirrhosis, HCC or mortality) compared to those who cleared both viruses from the
      sera. HBV of the genotype C is also a significant factor associated with adverse
      outcomes (cirrhosis, HCC or mortality) in patients with chronic hepatitis D in
      addition to genotype I HDV and age. However, most patients with chronic HDV
      infection have low or undetectable hepatitis B virus DNA levels. During
      longitudinal follow-up, genotype I HDV is the most important determinant
      associated with survival.

PMID- 16903227
TI  - Immunology of HDV infection.
AB  - Hepatitis delta virus (HDV) infection may occur as coinfection with hepatitis B
      virus (HBV) or as superinfection of a chronically HBV-infected patient. A strong
      antibody response is mounted, which persists for many years; however, it is not
      able to modulate the course of infection. In most cases the superinfection takes
      a chronic course. In patients with inactive disease (HDV PCR negative) an
      oligospecific T-helper cell immune response and a cytotoxic T-cell response were
      found, which were absent in patients with persistent viremia. The role of the
      cellular immune response in liver injury during acute infection has not been
      investigated. Vaccination strategies tested in the woodchuck model induced
      specific B- and T-cell responses but failed to protect from HDV infection.

PMID- 16903228
TI  - The woodchuck model of HDV infection.
AB  - The Eastern woodchuck, Marmota monax, has been a useful model system for the
      study of the natural history of hepadnavirus infection and for the development
      and preclinical testing of antiviral therapies. The model has also been used for
      hepatitis delta virus (HDV). In this chapter several new applications of the
      woodchuck model of HDV infection are presented and discussed. The development of
      a woodchuck HDV inoculum derived from a molecular clone has facilitated the
      analysis of viral genetic changes occurring during acute and chronic infection.
      This analysis has provided insights into one of the more important aspects of the
      natural history of HDV infection-whether a superinfection becomes chronic. These
      results could renew interest in further vaccine development. An effective therapy
      for chronic HDV infection remains an important clinical goal for this agent,
      particularly because of the severity of the disease and the inability of current
      hepadnaviral therapies to ameliorate it. The recent application of the woodchuck
      model of chronic HDV infection to therapeutic development has yielded promising
      results which indicate that targeting the hepadnavirus surface protein may be a
      successful therapeutic strategy for HDV.

PMID- 16903229
TI  - Virus-like particles associated with heart and skeletal muscle inflammation
      (HSMI).
AB  - The first cases of heart and skeletal muscle inflammation (HSMI), in Atlantic
      salmon Salmo salar were registered in 1999 in the Hitra/Froya area of Norway. The
      disease has since spread south to Rogaland, i.e. the southernmost county with
      salmon farming in Norway. The disease outbreaks usually start 5 to 9 mo after
      release into seawater but may occur as early as 2 wk after sea release. The
      present study focuses on possible pathogens associated with HSMI. It was not
      possible to find any parasites or bacteria that could explain HSMI, and none of
      the well-known viruses (infectious salmon anaemia virus, Norwegian salmonid
      alphavirus, infectious pancreatic necrosis virus, Atlantic salmonid
      paramyxovirus) were consistently present. Use of transmission electron microscopy
      showed the presence of epitheliocystis agent in 3 of 4 farms included in this
      study, and several virus-like particles. Type I and Type II virus particles,
      previously described for salmon suffering from haemorrhagic smolt syndrome (HSS),
      and erythrocytic inclusion body syndrome (EIBS) virus were consistently present
      in salmon suffering from HSMI in all 4 farms included in this study. The 2 HSS
      viruses (Type I and Type II) were also cultured in Atlantic salmon kidney (ASK)
      cells from salmon suffering from HSMI. However, a causal relationship between the
      observed virus particles and HSMI remains to be demonstrated.

PMID- 16903230
TI  - Viral gametocytic hypertrophy of Crassostrea gigas in France: from occasional
      records to disease emergence?
AB  - Viral gametocytic hypertrophy was reported for the first time in 2001 in Pacific
      oyster Crassostrea gigas in France. Since this date, the number of reported cases
      and the distribution area have increased every year; however, the cases are not
      associated with macroscopic signs or increased mortality rates. Both male and
      female gametes were hypertrophied and basophilic inclusions were observed in
      gamete nuclei. Transmission electron microscopy revealed the presence of viral
      particles in these intranuclear basophilic inclusions. These particles had
      characteristics similar to those of the Papillomaviridae and Polyoma viridae
      families: they were small, non-enveloped, icosahedral, and 44 to 56 nm in
      diameter. The viral particles were found in male, female and hermaphrodite
      oysters and no significant difference in viral infection was observed between
      those groups. The frequency of detection and the intensity of infection were low
      and no host defence reaction was recognised, suggesting that the viral particles
      had a weak impact on C. gigas. The viral particles described in the present study
      seem to be similar to these described in C. virginica in the USA and Canada and
      in C. gigas in Korea, but further studies are required to confirm their identity.
      The issue of a possible emergence of this infection is discussed.

PMID- 16903231
TI  - Dynamics of viral hemorrhagic septicemia, viral erythrocytic necrosis and
      ichthyophoniasis in confined juvenile Pacific herring Clupea pallasii.
AB  - Capture of wild, juvenile herring Clupea pallasii from Puget Sound (Washington,
      USA) and confinement in laboratory tanks resulted in outbreaks of viral
      hemorrhagic septicemia (VHS), viral erythrocytic necrosis (VEN) and
      ichthyophoniasis; however, the timing and progression of the 3 diseases differed.
      The VHS epidemic occurred first, characterized by an initially low infection
      prevalence that increased quickly with confinement time, peaking at 93 to 98%
      after confinement for 6 d, then decreasing to negligible levels after 20 d. The
      VHS outbreak was followed by a VEN epidemic that, within 12 d of confinement,
      progressed from undetectable levels to 100% infection prevalence with >90% of
      erythrocytes demonstrating inclusions. The VEN epidemic persisted for 54 d, after
      which the study was terminated, and was characterized by severe blood dyscrasias
      including reduction of mean hematocrit from 42 to 6% and replacement of mature
      erythrocytes with circulating erythroblasts and ghost cells. All fish with
      ichthyophoniasis at capture died within the first 3 wk of confinement, probably
      as a result of the multiple stressors associated with capture, transport,
      confinement, and progression of concomitant viral diseases. The results
      illustrate the differences in disease ecology and possible synergistic effects of
      pathogens affecting marine fish and highlight the difficulty in ascribing a
      single causation to outbreaks of disease among populations of wild fishes.

PMID- 16903232
TI  - Atypical strains of Aeromonas salmonicida contain multiple copies of insertion
      element ISAsa4 useful as a genetic marker and a target for PCR assay.
AB  - The species Aeromonas salmonicida includes a quite complex group of pathogens
      that cause a variety of diseases in fishes. Best studied strains of this species
      are those of the subspecies salmonicida also referred to as 'typical' A.
      salmonicida, which cause furunculosis in salmonids. Less completely understood
      are bacteria assigned to other subspecies, e.g. achromogenes and masoucida, or
      those that cannot be assigned to a recognized subspecies. These strains are
      referred to collectively as 'atypical' A. salmonicida and cause diseases distinct
      from furunculosis, primarily affecting non-salmonids. In the course of a study to
      investigate the suitability of the gene product of tapA as a subunit vaccine, we
      discovered several atypical strains of A. salmonicida in which the tapA gene was
      interrupted by an insertion sequence (IS). Subsequent Southern blot analyses
      indicated that nearly all atypical strains (27 of 29) examined carry many copies
      of this IS, which we named ISAsa4. Genetic characterization of this IS element
      revealed it to be a member of the IS5 family, subgroup IS903. Aside from the
      presence of ISAsa4 in several atypical strains, the nucleotide sequence of tapA
      was virtually identical to that found in typical strains. This finding suggests
      that ISAsa4 might be a major source of genetic diversity among atypical strains
      which, unlike typical strains, are genetically heterogeneous. The presence of
      ISAsa4 in atypical strains may also help explain the host tropism of atypical
      strains of this bacterium. Using information on the nucleotide sequences of
      ISAsa4 from atypical strains of A. salmonicida, primers were designed to
      selectively amplify genomic DNA from most atypical strains.

PMID- 16903234
TI  - Temperature-driven proliferation of Tetracapsuloides bryosalmonae in bryozoan
      hosts portends salmonid declines.
AB  - Proliferative kidney disease (PKD) is an emerging disease of salmonid fishes. It
      is provoked by temperature and caused by infective spores of the myxozoan
      parasite Tetracapsuloides bryosalmonae, which develops in freshwater bryozoans.
      We investigated the link between PKD and temperature by determining whether
      temperature influences the proliferation of T. bryosalmonae in the bryozoan host
      Fredericella sultana. Herein we show that increased temperatures drive the
      proliferation of T. bryosalmonae in bryozoans by provoking, accelerating and
      prolonging the production of infective spores from cryptic stages. Based on these
      results we predict that PKD outbreaks will increase further in magnitude and
      severity in wild and farmed salmonids as a result of climate-driven enhanced
      proliferation in invertebrate hosts, and urge for early implementation of
      management strategies to reduce future salmonid declines.

PMID- 16903233
TI  - Mortality and pathology in brown bullheads Amieurus nebulosus associated with a
      spontaneous Edwardsiella ictaluri outbreak under tank culture conditions.
AB  - Brown bullheads Amieurus nebulosus (family Ictaluridae) are commonly used as a
      sentinel of environmental contamination. These fish are not generally cultured
      under laboratory conditions and little is known about their disease
      susceptibility. Here we report an outbreak of disease due to Edwardsiella
      ictaluri in a laboratory population of tank-reared, wild-caught brown bullheads.
      The isolate was positively identified as E. ictaluri using standard
      bacteriological substrate utilization tests and a monoclonal antibody specific
      for this bacterium. This pathogen causes a significant disease in channel catfish
      Ictalurus punctatus and is associated with disease in other ictalurid and non
      ictalurid fishes. It appears that E. ictaluri is also a significant pathogen in
      brown bullheads and produces clinical signs and lesions similar but not identical
      to those observed in channel catfish. Since commercial sources of bullheads for
      laboratory tank studies are not available, precautions should be taken to prevent
      potential E. ictaluri disease outbreaks from wild-caught bullheads intended for
      laboratory research.

PMID- 16903235
TI  - Extra-intestinal localization of Goussia sp. (Apicomplexa) oocysts in Rana
      dalmatina (Anura: Ranidae), and the fate of infection after metamorphosis.
AB  - Although coccidia of the genus Goussia are common parasites of fish, only 2
      species have been described in amphibians: G. hyperolisi from common reed frogs
      Hyperolius viridiflavus from Kenya and G. neglecta from unspecified European
      water frogs of the genus Rana from Germany. The genus Goussia is characterized by
      an oocyst, with a fine oocyst wall, containing 4 dizoic sporocysts that are
      composed of 2 valves joined by a longitudinal suture and lacking a Stieda body
      (typical for the genus Eimeria). To date, infections in amphibians were generally
      considered to be specific to the intestine of aquatic larval stages (tadpoles) of
      anurans. Herein, we report on: (1) the presence of oocysts of Goussia sp. in an
      extra-intestinal location (liver) of tadpoles of the agile frog R. dalmatina and
      (2) the presence of oocysts in the liver of both juvenile and subadult R.
      dalmatina. These observations represent novel traits for Goussia infections in
      amphibians; they may explain the vertical transmission of Goussia in tadpoles.

PMID- 16903236
TI  - Influence of salinity on prevalence of the parasite Loxothylacus panopaei in the
      xanthid Panopeus obesus in SW Florida.
AB  - This study was conducted to examine the potential influence of salinity, a proxy
      for freshwater inflow, on the prevalence of the castrator parasite Loxothylacus
      panopaei on saltmarsh mud crabs Panopeus obesus on SW Florida oyster reefs.
      Spatial and seasonal patterns of the presence of potential host crabs and the
      prevalence of the parasite were assessed in the Caloosahatchee, Estero, and Faka
      Union estuaries. Lift nets (1 m2) containing 5 1 of oyster clusters were deployed
      on intertidal reefs at 3 sites along the salinity gradient of each estuary. Nets
      were deployed during 3 seasonally dry and 3 seasonally wet months for a period of
      30 d. P. obesus densities tended to increase downstream in higher salinity
      waters, with crabs being absent from the upper station in the Caloosahatchee
      during both seasons and absent from the upper station of the Faka Union during
      wet months. Parasite prevalence was reduced upstream in each estuary during wet
      months compared to dry months, and for those estuaries that experienced higher
      relative levels of freshwater inflow. Furthermore, parasite prevalence was
      positively correlated with the mean salinity of capture of host crabs. Based on
      the distribution of P. obesus and the above patterns related to salinity, it
      appears that freshwater inflow and seasonal rains might regulate the prevalence
      of this parasite in SW Florida by creating spatiotemporal, low salinity refuges
      for its host.

PMID- 16903237
TI  - Protozoan parasites in cultured mussels Mytilus galloprovincialis in the
      Thermaikos Gulf (north Aegean Sea, Greece).
AB  - The protozoans Ancistrum mytili (Oligohymenophorea: Ancistridae) and Marteilia
      refringens/maurini (Marteiliidea: Marteiliidae) were found parasitizing cultured
      mussels Mytilus galloprovincialis L. in the Thermaikos Gulf (north Aegean Sea,
      Greece). The former did not affect the condition index of infected mussels, in
      contrast to the latter, which did so and which also induced hemocyte infiltration
      in the affected digestive epithelium. The prevalence of both parasites was
      relatively high in a polluted area.

PMID- 16903238
TI  - Occurrence of Atractolytocestus huronensis (Cestoda, Caryophyllaeidae) in German
      pond-farmed common carp Cyprinus carpio.
AB  - Up to now, the caryophyllid cestode Atractolytocestus huronensis Anthony, 1958, a
      parasite of common carp, has attracted little attention in Germany. Based on
      recent publications from the Czech Republic and Hungary, it appears probable that
      this cestode may be increasingly common in Germany. There is a strong connection
      between the occurrence of A. huronensis and imports of common carp from the Czech
      Republic and southern Germany. Although in most cases no clinical alterations in
      parasitized carp have been observed, care should be taken to avoid further
      dissemination and to prevent possible losses in commercial pond farming.

PMID- 16903239
TI  - The diagnosis and treatment of infertility. One person's philosophic approach.
AB  - PURPOSE: To justify and at the same time present caveats from one reproductive
      endocrinologist discussing diagnoses and treatment of various aspects of
      infertility. METHODS: Sources of basis of knowledge revealed. RESULTS: Sources
      for chapter writing includes personal experience, publications (predominantly
      from the author with some additional sources), national and international
      meetings, reading of various infertility journals and textbooks. CONCLUSIONS:
      Hopefully, the chapters will be provocative and provide new insights into
      diagnosis and treatment of infertility. Only areas where the author is most
      experienced will be discussed. The author promises a non-conventional approach
      which will lead to lots of controversy.

PMID- 16903240
TI  - Pharmacological options in resistent ovary syndrome and premature ovarian
      failure.
AB  - PURPOSE: To present methods of treating women in apparent ovarian failure to
      allow them to ovulate and conceive. METHODS: Ethinyl estradiol was used to lower
      elevated serum follicle stimulating hormone (FSH) levels to restore down
      regulated FSH receptors on the follicle. Ovulation and pregnancy rates were then
      determined. Aggressive progesterone (P) therapy in the luteal phase was also
      used. Lowering elevated serum FSH with gonadotropin releasing hormone agonists
      was also successful in inducing ovulation in these patients. RESULTS: Several
      anecdotal studies have demonstrated that ethinyl estradiol therapy can induce
      ovulation in women in apparent menopause and achieve live births. CONCLUSIONS:
      The advantage of ethinyl estradiol over other estrogens to induce ovulation in
      hypergonadotropic women is that it does not cross-react in the assay for serum
      estradiol and can allow detection of estradiol secretion by the follicle. Thus
      estrogen therapy is by far the most effective treatment.

PMID- 16903241
TI  - Successful pregnancies from embryos cryopreserved more than ten years: two case
      reports.
AB  - PURPOSE: To determine the efficacy of using embryos cryopreserved more than ten
      years in a donor embryo program. METHODS: Embryos were cryopreserved using a
      simplified freezing protocol and then donated for anonymous use after the donor
      had had a successful pregnancy and was sure she did not want to conceive again.
      RESULTS: Two women in the donor embryo program transferred embryos that had been
      cryopreserved longer than ten years. Both patients delivered healthy babies.
      CONCLUSIONS: Embryos cryopreserved over ten years can result in successful
      pregnancies.

PMID- 16903242
TI  - Postpartum hemorrhage: practical approach to a life-threatening complication.
AB  - Postpartum haemorrhage (PPH) occurs in 5% of all deliveries and is responsible
      for a major part of maternal mortality. Adequate attendance to this complication
      can mean the difference between life and death. A well-trained staff together
      with clear and simple guidelines can make a significant difference to the
      patient. The aim of this article is to offer a practical guide for the management
      of PPH; a flowchart is presented. When faced with refractory hemorrhage, one can
      switch to interventional therapy or surgery. Efficiency and speed play a key part
      in the approach to this life threatening bleeding.

PMID- 16903243
TI  - Estrogen effects on the vaginal pH, flora and cytology in late postmenopause
      after a long period without hormone therapy.
AB  - In this report we evaluated the action of conjugated equine estrogens (CEE) on
      vaginal symptoms, cytology, pH, and flora in late postmenopausal women without
      any previous hormone therapy. The study was a randomized, double-blind, placebo
      controlled trial with 48 late postmenopausal women who received placebo or
      unopposed CEE (0.625mg/day of CEE orally) during three months of treatment.
      Vaginal and sexual complaints were evaluated through daily diary cards. We
      analyzed vaginal changes through cytology and pH measurements. After three months
      of treatment, 20% of placebo-treated patients and 80% of the CEE-treated patients
      reported improvement in vaginal dryness and irritation. In the latter group, the
      vaginal cells and Lactobacillus increased and the vaginal pH decreased, without
      other changes in sexual complaints. We concluded that estrogen ameliorated the
      genital tract of late postmenopausal women without any previous hormone therapy.

PMID- 16903244
TI  - Reproductive outcome in patients treated by oral methotrexate or laparoscopic
      salpingotomy for the management of tubal ectopic pregnancy.
AB  - OBJECTIVE: To determine the reproductive outcome of women who have received
      methotrexate or been treated by laparoscopic salpingotomy (LS) for ectopic tubal
      pregnancy. STUDY DESIGN: The study consisted of 123 participants, all women with
      tubal pregnancies, who had been treated either by methotrexate per os or by
      laparoscopic salpingotomy. The reproductive outcome of these women was estimated
      after a follow-up time-period of ten years. RESULTS: In the methotrexate group,
      consisting of 34 women, the fertility rate was 82% with a mean interval time to
      conceive of 9.4 months after the treatment. In the group treated by LS,
      consisting of 89 women, the fertility rate was 82.6% and the mean interval time
      to conceive was 11.7 months. CONCLUSION: The reproductive outcome of the women
      who received either per os treatment of methotrexate or LS for tubal pregnancy,
      remains high. Both therapeutic methods constitute reliable solutions for managing
      ectopic pregnancy.

PMID- 16903245
TI  - Regression rate of clinical HPV infection of the lower genital tract during
      pregnancy after laser CO2 surgery.
AB  - The objective of the study was to evaluate the effects of laser CO2 surgery
      during pregnancy to prevent clinical HPV infection recurrence after delivery and
      vertical infection. A case-control study was performed on 280 pregnant women
      affected by clinical HPV infection treated during pregnancy with 256 women
      treated three months after delivery. Follow-up was performed for a minimum of
      three colposcopic examinations for two years. Recurrence rates were calculated
      considering the number of positive findings for at least one colposcopic
      examination confirmed by biopsy after a negative control in a year. Statistical
      comparison of rates was performed by chi-squared and Fisher's exact test.
      Recurrence rates were higher in the women treated in postpartum (p < .01) than in
      the group treated during gestation (p < .005). Clinical HPV infections treated
      during the second trimester of pregnancy showed a sensitive decrease in
      recurrence-rate of infection. Rarity of respiratory papillomatosis makes
      conclusions inconsistent for the prevention of vertical infection.

PMID- 16903246
TI  - Preeclampsia and birthweight by gestational age in singleton pregnancies in
      Flanders, Belgium: a prospective study.
AB  - PURPOSE: Recent studies have questioned the relationship between low birthweight
      and hypertension in pregnancy, especially in term pregnancies. We aimed to
      analyse the influence of chronic hypertension, preeclampsia, gestational
      hypertension and superimposed preeclampsia on birth weight in singleton
      pregnancies at different gestational ages. METHODS: Between January 1, 2001 and
      December 31, 2002 data on hypertension (subdivided in chronic hypertension,
      preeclampsia, gestational hypertension, superimposed preeclampsia and eclampsia)
      were collected prospectively for all deliveries in the region of Flanders,
      Belgium. Multiple pregnancies and patients with diabetes were excluded from
      analysis. Multiple linear regression was performed to construct a model for the
      prediction of birthweight and to determine the contribution of hypertension.
      RESULTS: Hypertension was diagnosed in 5,284 of 111,007 (4.8%) singleton
      pregnancies, and of these 647 had chronic hypertension (0.6% of the total group),
      2,253 (2%) gestational hypertension, 2,244 (2%) preeclampsia and 140 (0.1%)
      superimposed preeclampsia. Birthweight less than 2,500 g was most frequent in the
      preeclamptic group and less frequent in case of gestational hypertension, but in
      all hypertensive groups it was statistically more frequent compared to the
      normotensive pregnancies. Before 26 weeks' gestational age the presence of any
      kind of hypertension did not influence birthweight. From 26 weeks on preeclampsia
      contributed to a lower birthweight. Gestational hypertension resulted in a lower
      birthweight between 28 and 34 weeks, but not before or after this period.
      Superimposed preeclampsia only had an effect between 32 and 34 weeks and chronic
      hypertension only marginally contributed to birthweight. A relation with both a
      high birthweight (> 4000 g) and birthweight < 2500 g was found in term
      gestational hypertension and preeclampsia. CONCLUSION: At an early gestational
      age (less then 26 weeks) hypertension is not a significant factor influencing
      birthweight. Uncomplicated chronic hypertension is not an important factor
      determining birthweight but preeclampsia is. Gestational hypertension influences
      birthweight in a limited period between 28 and 34 weeks of gestational age. When
      hypertensive pregnancies reach term they tend to result both in more babies
      weighing < 2,500 g and > 4,000 g.

PMID- 16903247
TI  - Placental umbilical cord whole blood transfusion to combat anemia in the
      background of tuberculosis and emaciation and its potential role as an immuno
      adjuvant therapy for the under-resourced people of the world.
AB  - Tuberculosis causes approximately 1.5 billion latent infections, 8 million new
      clinical cases, and 3 million deaths annually, making it the most prevalent
      infectious disease in the world. Anemia and malnutrition are essential
      comorbidities with tuberculosis. Cord blood, because of its rich mix of fetal and
      adult hemoglobin, high platelet and WBC counts, and a plasma filled with cytokine
      and growth factors, as well as its hypo-antigenic nature and altered metabolic
      profile, has all the potential of a real and safe alternative to adult blood
      transfusion. We transfused 106 units (48 ml-148 ml mean 81 ml +/- 6.6 ml SD,
      median 82 ml, mean packed cell volume 49.4 +/- 3.1 SD, mean percent hemoglobin
      concentration 16.3 g/dl +/- 1.7 g/dl SD) of placental umbilical cord whole blood
      (from 1 April 1999 to 1st 2005) after lower uterine cesarean section from
      consenting mothers to 21 informed consenting patients with tuberculosis who had
      percent plasma hemoglobin of 8 g/dl or less. After collection, the blood was
      immediately transfused following the standard adult blood transfusion protocol.
      Each case was passed through the institutional ethical committee. The patients
      received 2-21 units of freshly collected placental umbilical cord blood without
      encountering any clinical, immunological or non-immunological reactions. Three
      days after completion of the placental umbilical cord blood transfusion, the
      peripheral blood hematopoietic stem cell (CD34) estimation revealed a rise from
      the pretransfusion base level (.09%), varying from 2.99% to 33%, which returned
      to base level in 66.66% at the three-month CD34 re-estimation, without provoking
      any clinical graft vs host reaction in any of the patients.

PMID- 16903248
TI  - Prenatal diagnosis of Wolf-Hirschhorn syndrome (4p-) in association with
      congenital diaphragmatic hernia, cystic hygroma and IUGR.
AB  - Wolf-Hirschhorn syndrome (WHS) is a rare distinct clinical entity caused by a
      deletion of the short arm of chromosome 4. We report a case in which intrauterine
      growth restriction (IUGR), severe oligohydramnios, left-sided congenital
      diaphragmtic hernia (CDH), and cystic hygroma were detected by prenatal
      ultrasound examination at 27 weeks of gestation. A 29-year-old gravida 3, para 2,
      woman was referred at 26 weeks' gestation with suspicion of IUGR and cystic
      hygroma. Sonographic examination revealed IUGR with severe oligohydramnios,
      increased nuchal fold with cystic hygroma (left-sided diaphragmatic defect of
      Bochdalek type), and congenital diaphragmatic hernia. Chromosome analysis
      revealed a 46, XX, del(4)(p15.2) karyotype. Autopsy confirmed the ultrasound
      findings. Congenital diaphragmatic hernia (CDH) has rarely been described to be
      associated with WHS. CDH and cystic hygroma can lead to a diagnosis of this
      syndrome very early in life. We recommend genetic evaluation of a fetus with
      cystic hygroma, IUGR and CDH taking into consideration 4p deletion syndrome.

PMID- 16903249
TI  - Vaginal and uterine pressure response to semen deposition into the vagina and
      uterus: human study.
AB  - PURPOSE OF INVESTIGATION: The effect of semen deposition in the vagina or uterine
      cavity on both uterine and vaginal pressure has scarcely been reported in the
      literature. We investigated the hypothesis that semen deposition in the vagina or
      uterus effects changes in their pressure. METHODS: The study comprised 27 healthy
      women volunteers (mean age 36.4 +/- 11.6 years). Both uterine and vaginal
      pressure were measured under basal conditions and on semen or saline deposition
      in the vagina and uterus. RESULTS: Upon semen deposition in the vagina, the
      vaginal pressure showed no significant changes (p > 0.05) while the uterine
      pressure exhibited a significant intermittent rise (p < 0.05). Semen deposition
      into the uterine cavity caused no vaginal pressure changes (p > 0.05) while the
      uterine pressure exhibited an intermittent increase (p < 0.01). Saline injection
      into the vagina or uterus showed no significant pressure changes (p > 0.05).
      CONCLUSION: Semen deposition into the vagina or uterine cavity was associated
      with uterine pressure elevation that might eventually help transport the sperm to
      the oviduct. Further studies are required to define the substances responsible
      for this effect.

PMID- 16903250
TI  - Septate uterus: reproductive outcome after hysteroscopic metroplasty.
AB  - OBJECTIVE: To evaluate hysteroscopic metroplasty and its effect on reproductive
      outcome. STUDY DESIGN: Seventy-five patients consulted for uterine septum between
      January 1996 to December 2000 at "La Sapienza" University in Rome were included
      in the study. RESULTS: Forty patients attempted pregnancy and a total of 30
      spontaneous pregnancies resulted (75% pregnancy rate). The uterine cavity was
      normal at hysteroscopic follow-up in 68% of cases. CONCLUSION: Correction of
      uterine septum improves pregnancy outcome of patients. Broadening the indications
      for hysteroscopic metroplasty should be encouraged for patients who desire to
      conceive.

PMID- 16903251
TI  - Leptin: pharmacological aspects in gynecology.
AB  - Hematic levels of leptin vary in relation to numerous metabolic factors and are
      able to interact in perfect synchrony with the hormones involved in the
      hypothalamus-pituitary-ovarian axis during the various phases of the reproductive
      cycle. In general it is maintained that the complex and multiple action
      mechanisms of leptin need to be clarified by further in-depth research studies.
      It is likely that valid pharmacological applications of leptin will be found for
      human use although it is too premature to talk about concrete pharmacological
      answers and to formulate the relative complete technical protocols. In medicine
      the therapeutic use of leptin for humans has been reported in only a few cases.
      In fact human recombinant leptin has already been administered in gynecology for
      hypothalamic amenorrhea with precise protocols. In addition, very recent studies
      have provided the basis for new strategies to be developed concerning the use of
      leptin to fight multiple sclerosis. At present there are considerable technical
      and economic problems in the production of leptin on a large scale. Most likely
      these problems will be overcome in the foreseeable future, and will involve new
      techniques related to genetics, cellular reprograming, and stem cells. In fact,
      new pharmacogenetic research has provided encouraging results for the production
      in industrial quantities of a more effective and fail-proof leptin. Even
      considering that norms have not yet been proposed for pharmacological
      interventions with leptin for use directly on humans, in our work we have studied
      by immunohistochemistry methods the distribution of leptin and its receptor (Ob
      R) in the ovaries of the female dog as a biological model, in the pre- and
      postpubertal phases and in other phases of the ovarian cycle. Given the
      hypothesis that the information obtained from immunohistochemical localization of
      the hormone and its receptor in various ovarian structures is transferable to
      humans, it could be useful to define therapeutic protocols based on the effective
      role of leptin and its receptor in folliculogenesis.

PMID- 16903252
TI  - A preliminary report of 123 units of placental umbilical cord whole blood
      transfusion in HIV-positive patients with anemia and emaciation.
AB  - Cord blood, because of its rich mix of fetal and adult hemoglobin, high platelet
      and WBC counts, and a plasma filled with cytokine and growth factors, as well as
      its hypo antigenic nature and altered metabolic profile, has all the potential of
      a real and safe alternative to adult blood transfusion. Our team's experience
      (from 1st April 1999 to 1st July 2005) with 123 units of placental umbilical cord
      whole blood (62 ml-154 ml mean 85 ml +/- 8.4 ml SD, median 82 ml, mean packed
      cell volume 48.8 +/- 4.2 SD, mean percent hemoglobin concentration 16.3 g/dl +/-
      1.6 g/dl SD; after collection the blood was immediately preserved in a
      refrigerator and transfused within 72 hours of collection) collected after lower
      uterine cesarean section (LUCS), and the transfusion to 16 consenting HIV
      positive patients (12 cases had full blown AIDS) with anemia and emaciation is
      presented here. On the basis of our preliminary experience of cord blood
      transfusion, we are of the opinion that umbilical cord whole blood transfusion is
      safe in HIV-positive patients. This blood has the potential to carry more oxygen
      than adult blood and it does not trigger any clinical, immunological or non
      immunological reaction after its transfusion to an adult host with a HIV-positive
      status. Apart from the correction of anemia, there was also definite improvement
      in the energy and fatigue levels in individuals with HIV, i.e., physical
      functioning, a sense of well-being and weight gain from two to five pounds,
      within three to ten months of the commencement of transfusion. There was also an
      immediate rise in CD34 levels of peripheral blood in the HLA-randomized host
      after transfusion, without any clinical graft vs host reaction.

PMID- 16903253
TI  - Prenatal diagnosis of vasa previa through color Doppler and three-dimensional
      power Doppler ultrasonography. A case report.
AB  - Vasa previa occurs in pregnancy when one of the membrane vessels extends down to
      the level of the internal cervical os, ahead of the fetal presenting part and
      unsupported by the placenta tissue or umbilical cord. The rupture of the vessels
      might happen spontaneously or artificially and frequently results in fetal
      exsanguination and demise. Ultrasound prenatal diagnosis is highly important as
      it allows the identification of patients at risk, thus an elective cesarean can
      be performed before rupture the membranes. We report a case of vasa previa
      diagnosed through color Doppler mode in the 30th week of gestation, emphasizing
      the contribution of three-dimensional power Doppler to the adequate mapping of
      aberrant vessels, which greatly contributed to the success of the perinatal
      result.

PMID- 16903254
TI  - Idiopathic orthostatic cyclic edema as a unique etiology for vasomotor flushing
      in a normal estrogenic woman with normal day 3 follicle stimulating hormone--case
      report.
AB  - PURPOSE: To describe a unique cause and therapy for vasomotor flushing. METHODS:
      Serum follicle stimulating hormone (FSH) and estradiol, renal and liver function
      studies and urinalysis were performed as well as a water load test. RESULTS: All
      laboratory tests were normal but the water load test showed inadequate four-hour
      urine excretion when she was erect but normal when supine. Complete relief from
      vasomotor symptoms occurred shortly after treatment with sympathomimetic amines.
      CONCLUSIONS: Idiopathic orthostatic cyclic edema can cause vasomotor flushing
      even with normal estrogen and serum FSH, and treatment of the edema state with
      the drug of choice dextroamphetamine sulfate can effectively control these
      symptoms.

PMID- 16903255
TI  - A rare case of early onset nephrotic syndrome in pregnancy.
AB  - Nephrotic syndrome occurs very rarely, about 0.012-0.025% of all pregnancies.
      Here, we report a rare case of early onset nephrotic syndrome developing de novo
      in the 17th week of pregnancy. A renal biopsy was done and the specimens revealed
      typical features of focal segmental glomerulosclerosis. The patient had a
      progressive clinical course of disease despite steroid treatment. Suffering from
      severe intrauterine growth restriction, the fetus died in utero. After delivery,
      steroid treatment was continued. The patient had normal renal function with a
      decrease in proteinuria in the second and fifth month postpartum. This report
      points out the poor fetal prognosis associated with an early onset nephrotic
      syndrome. Pregnant patients with early onset nephrotic syndrome should be
      carefully evaluated for the presence of chronic renal disease, and primary renal
      pathology should be included in the differential diagnosis of massive proteinuria
      in early pregnancy.

PMID- 16903256
TI  - Control of stress propagation in the cytoplasm by prestress and loading
      frequency.
AB  - One fundamental question in cell biology is how mechanical stresses are
      distributed inside the cytoplasm. Recently we have developed a synchronous
      detection approach to map cytoplasmic displacements and stresses using yellow
      fluorescent protein tagged mitochondria as fiducial markers of the cytoskeleton
      (CSK) in response to a localized load applied via an RGD-coated magnetic bead
      (7). We have shown that stresses are propagated to remote sites in the cytoplasm,
      a finding that contradicts continuum model predictions. Here we show that long
      distance force propagation in the cytoplasm was abolished when the contractile
      prestress in the CSK was lowered by relaxing agents and enhanced when the
      prestress was increased by contractile agonists. Surprisingly, when the loading
      frequency was varied from 0.03 Hz to 30 Hz, the total area of induced
      displacements (an index of the extent of stress propagation) first increased with
      loading frequency and then decreased with loading frequency. These results
      demonstrate that the long distance force propagation in living adherent cells
      might be controlled by the level of contractile prestress in the CSK and by the
      loading frequency.

PMID- 16903258
TI  - Three-dimensional molecular phase separation and flow patterns with novel
      multilevel fluidics.

PMID- 16903257
TI  - Adhesive force of human hepatoma HepG2 cells to endothelial cells and expression
      of E-selectin.
AB  - Expression of adhesion molecules may play an important role in the interaction of
      tumor cells with vascular endothelial cells during tumor invasion and metastasis.
      In this study, the adhesive force of human hepatoma HepG2 cells to human
      umbilical vein endothelial cells (HUVECs) was investigated using a micropipette
      aspiration technique. Expression of an adhesion molecule, E-selectin, was also
      observed by immunofluorescence microscopy. In particular, the adhesive force
      after stimulation of HUVECs with recombinant human interleukin-1beta (rhIL-1beta)
      was examined. The results demonstrated that the adhesive force of HepG2 cells to
      stimulated HUVECs is significantly higher than that of unstimulated control
      cells, and that immunofluorescence of E-selectin in stimulated HUVECs showed a
      higher fluorescent intensity compared to control cells. Moreover, addition of
      monoclonal anti-human E-selectin decreased the adhesive force of HepG2 cells to
      stimulated HUVECs by 50%. These results suggest that endothelial E-selectin may
      be a main mediator of carcinoma metastasis of malignant tumor through blood
      circulation, possibly increasing the adhesive force of human hepatoma HepG2 cells
      to HUVECs in the early stage of metastases.

PMID- 16903260
TI  - Hospitalists make a mark. Emerging specialty linked to shorter lengths of stay
      and improved mortality, but not to lower costs, Solucient finds.

PMID- 16903259
TI  - Kinetics analysis of binding between melanoma cells and neutrophils.
AB  - It has been determined previously that polymorphonuclear leukocytes, or PMNs, can
      facilitate melanoma cell extravasation through the endothelium under shear
      conditions. The interactions between melanoma cells and PMNs are mediated by the
      beta2-integrins expressed by PMNs and intercellular adhesion molecules (ICAM-1)
      expressed on melanoma cells. In this study, the kinetics of these interactions
      was studied using a parallel plate flow chamber. The dissociation rates were
      calculated under low force conditions for ICAM-1 interactions with both beta2
      integrins, LFA-1 (CD11a/CD18) and Mac-1 (CD11b/CD18), together and separately by
      using functional blocking antibodies on PMNs. The kinetics of PMNs stimulated
      with IL-8 was also determined. It was concluded that the small number of
      constitutively expressed active beta2-integrins on PMNs are sufficient to bind to
      ICAM-1 expressed on melanoma cells and that the intrinsic dissociation rate for
      these adhesion molecules appear to be more dependent on what method is used to
      determine them than on what cells express them.

PMID- 16903261
TI  - From the top down. Boards play key role in clinical improvement: study.

PMID- 16903262
TI  - Study links TiO2 nanoparticles with potential for brain-cell damage.

PMID- 16903263
TI  - Are red blood cells defenseless against smaller nanoparticles?

PMID- 16903264
TI  - Bacteria may break down popular flame retardant to produce toxics.

PMID- 16903265
TI  - Capturing "real-world" aircraft emissions.

PMID- 16903266
TI  - Mercury model at the top of its game?

PMID- 16903267
TI  - Mis-lead.

PMID- 16903268
TI  - Assessing the risks of manufactured nanomaterials.

PMID- 16903269
TI  - Titanium dioxide (P25) produces reactive oxygen species in immortalized brain
      microglia (BV2): implications for nanoparticle neurotoxicity.
AB  - Concerns with the environmental and health risk of widely distributed, commonly
      used nanoparticles are increasing. Nanosize titanium dioxide (TiO2) is used in
      air and water remediation and in numerous products designed for direct human use
      and consumption. Its effectiveness in deactivating pollutants and killing
      microorganisms relates to photoactivation and the resulting free radical
      activity. This property, coupled with its multiple potential exposure routes,
      indicates that nanosize TiO2 could pose a risk to biological targets that are
      sensitive to oxidative stress damage (e.g., brain). In this study, brain
      microglia (BV2) were exposed to a physicochemically characterized (i.e.,
      dispersion stability, particle size distribution, and zeta potential)
      nanomaterial, Degussa P25, and cellular expressions of reactive oxygen species
      were measured with fluorescent probes. P25's zeta potentials, measured in cell
      culture media and physiological buffer were -11.6 +/- 1.2 mV and -9.25 +/- 0.73
      mV, respectively. P25 aggregation was rapid in both media and buffer with the
      hydrodynamic diameter of stable P25 aggregates ranging from 826 nm to 2368 nm
      depending on the concentration. The biological response of BV2 microglia to
      noncytotoxic (2.5-120 ppm) concentrations of P25 was a rapid (<5 min) and
      sustained (120 min) release of reactive oxygen species. The time course of this
      release suggested that P25 not only stimulated the immediate "oxidative burst"
      response in microglia but also interfered with mitochondrial energy production.
      Transmission electron microscopy indicated that small groups of nanosized
      particles and micron-sized aggregates were engulfed bythe microglia and
      sequestered as intracytoplasmic aggregates after 6 and 18 h exposure to P25 (2.5
      ppm). Cell viability was maintained at all test concentrations (2.5-120 ppm) over
      the 18 h exposure period. These data indicate that mouse microglia respond to
      Degussa P25 with cellular and morphological expressions of free radical
      formation.

PMID- 16903270
TI  - Interaction of fine particles and nanoparticles with red blood cells visualized
      with advanced microscopic techniques.
AB  - So far, little is known about the interaction of nanoparticles with lung cells,
      the entering of nanoparticles, and their transport through the blood stream to
      other organs. The entering and localization of different nanoparticles consisting
      of differing materials and of different charges were studied in human red blood
      cells. As these cells do not have any phagocytic receptors on their surface, and
      no actinmyosin system, we chose them as a model for nonphagocytic cells to study
      how nanoparticles penetrate cell membranes. We combined different microscopic
      techniques to visualize fine and nanoparticles in red blood cells: (I)
      fluorescent particles were analyzed by laser scanning microscopy combined with
      digital image restoration, (II) gold particles were analyzed by conventional
      transmission electron microscopy and energy filtering transmission electron
      microscopy, and (III) titanium dioxide particles were analyzed by energy
      filtering transmission electron microscopy. By using these differing microscopic
      techniques we were able to visualize and detect particles < or = 0.2 microm and
      nanoparticles in red blood cells. We found that the surface charge and the
      material of the particles did not influence their entering. These results suggest
      that particles may penetrate the red blood cell membrane by a still unknown
      mechanism different from phagocytosis and endocytosis.

PMID- 16903271
TI  - Antibacterial activity of fullerene water suspensions: effects of preparation
      method and particle size.
AB  - Fullerene research in biological systems has been hindered by the compound's
      relative insolubility in water. However, C60 molecules can be made to aggregate,
      forming stable fullerene water suspensions (FWS) whose properties differ from
      those of bulk solid C60. There are many different protocols for making FWS. This
      paper explores four of these methods and establishes the antibacterial activity
      of each resulting suspension, including a suspension made without intermediary
      solvents. The aggregates in each polydisperse suspension were separated by size
      using differential centrifugation and tested for antibacterial activity using
      Bacillus subtilis as a test organism. All suspensions exhibited relatively strong
      antibacterial activity. Fractions containing smaller aggregates had greater
      antibacterial activity, although the increase in toxicity was disproportionately
      higher than the associated increase in putative surface area. This suggests the
      need for improved understanding of the behavior of FWS towards organisms and in
      the environment to determine how C60 can be safely used and disposed.

PMID- 16903272
TI  - In vitro interactions between DMSA-coated maghemite nanoparticles and human
      fibroblasts: A physicochemical and cyto-genotoxical study.
AB  - Although the current production of oxide nanoparticles may be modest, the wide
      range of proposed applications and forecasted growth in production has raised
      questions about the potential impact of these nanoparticles on the environment
      and human health. Iron oxide nanoparticles have been proposed for an increasing
      number of biomedical applications although in vitro toxicity depending on the
      particles coating has been evidenced. The aim of this study was to examine the
      potential in vitro cyto- and genotoxicity on human dermal fibroblasts of DMSA
      coated maghemite nanoparticles (NmDMSA) as a function of well-defined
      physicochemical states. Well-stabilized NmDMSA produced weak cytotoxic and no
      genotoxic effects. This is attributed in part to the DMSA coating, which serves
      as a barrier for a direct contact between nano-oxide and fibroblasts, inhibiting
      a potential toxic effect.

PMID- 16903273
TI  - In vitro cytotoxicity of oxide nanoparticles: comparison to asbestos, silica, and
      the effect of particle solubility.
AB  - Early indicators for nanoparticle-derived adverse health effects should provide a
      relative measure for cytotoxicity of nanomaterials in comparison to existing
      toxicological data. We have therefore evaluated a human mesothelioma and a rodent
      fibroblast cell line for in vitro cytotoxicity tests using seven industrially
      important nanoparticles. Their response in terms of metabolic activity and cell
      proliferation of cultures exposed to 0-30 ppm nanoparticles (microg g(-1)) was
      compared to the effects of nontoxic amorphous silica and toxic crocidolite
      asbestos. Solubility was found to strongly influence the cytotoxic response. The
      results further revealed a nanoparticle-specific cytotoxic mechanism for uncoated
      iron oxide and partial detoxification or recovery after treatment with zirconia,
      ceria, or titania. While in vitro experiments may never replace in vivo studies,
      the relatively simple cytotoxic tests provide a readily available pre-screening
      method.

PMID- 16903274
TI  - Cadmium--copper antagonism in seaweeds inhabiting coastal areas affected by
      copper mine waste disposals.
AB  - Cadmium and copper accumulation by macroalgae was studied in a coastal area
      exposed to upwelling events and high levels of Cu, the latter resulting from mine
      disposals. Eight species were studied, and all had very high concentrations of Cd
      outside of the Cu-contaminated area. Cu in algal tissues was much higher in
      contaminated than in reference sites. High Cu appeared to suppress Cd
      bioaccumulation; Cd in algal tissues was much lower in the Cu-contaminated area
      than in the reference sites. Transplant experiments with Lessonia nigrescens
      revealed a depuration of Cd in individuals transplanted to areas with high Cu.
      However, Cd depuration occurs more slowly than Cu uptake. These differences
      suggest that while Cd and Cu are linked mechanistically, itis nota simple
      substitution. Overall, the work confirms that macroalgae are useful indicators of
      metal contamination and may be used as in situ biomonitors for labile forms of
      metals, like free Cu2+. However, antagonistic relationships between metals must
      be clearly understood in order to properly interpret their concentrations in
      macroalgae.

PMID- 16903275
TI  - Use of sunfish and stoneroller minnows as real-time in situ biomonitors of PCB
      contamination in freshwater streams.
AB  - A long-term polychlorinated biphenyl (PCB) monitoring study was conducted fortwo
      moderately impacted freshwater streams in Kentucky. Streamwater, sediment, and
      fish were analyzed for Aroclors 1248, 1254, and 1260 during 1988-2005. Only 8 of
      263 water samples showed detectable PCBs. The low occurrences of PCB detections
      in streamwater indicated that PCBs were transitory in the water column, rapidly
      mobilizing into biotic and sediment compartments. One component of this study
      focused on species-specific patterns of PCB residues in fish, especially the
      green sunfish (Lepomis cyanellus), longear sunfish (L. megalotis), bluegill (L.
      macrochirus), and stoneroller minnow (Campostoma anomalum). Stoneroller minnows
      had higher PCB concentrations and increased frequency of detection when compared
      to sport fish. Aroclor 1248 was detected 80% of the time in stoneroller minnows
      from Big Bayou creek, whereas it was only detected in 25-39% of sport fish. In
      comparison, Aroclors 1254 and 1260 in sport fish were detected 49-69% of the
      time. These results indicate that higher chlorinated PCB congeners found in
      Aroclors 1254 and 1260 were not as readily metabolized and excreted by sport
      fish. No relationships were found between sunfish age and PCB concentrations,
      which demonstrated that sunfish exposed to low PCB contamination can effectively
      regulate PCBs, regardless of age. In addition, at low PCB levels (<0.50
      microg/g), green sunfish body burden did not correlate with lipid content. A
      certain PCB threshold concentration, > or = 1.00 microg/g, must be exceeded
      before correlations between PCB body burden and lipid content are observed. These
      results indicate that, at least for species such as the sunfish, the use of the
      octanol-water partition coefficient (Kow) under low-level PCB exposure would
      appear to have little predictive value. Studies by Sanborn et al. (1975) found
      the green sunfish to be particularly adept at metabolizing organochlorine
      compounds and PCBs. This field study supports their laboratory findings. Green
      sunfish may have an enhanced P450 system, or due to low body lipid content, more
      effectively shunt PCBs into metabolic pathways that detoxify these compounds.

PMID- 16903276
TI  - Exposure to PBDEs and PCDEs associated with the consumption of edible marine
      species.
AB  - In the present study, the concentrations of PBDEs and PCDEs were determined in 14
      edible marine species widely consumed by the population of Catalonia (Spain). The
      daily intake of PBDEs and PCDEs associated with this consumption was also
      determined. A total of 42 composite samples were analyzed by HRGC/HRMS. The
      highest PBDE levels (ng/kg wet weight) were found in salmon (2015) followed by
      mackerel, swordfish, and red mullet (1124, 978, and 769, respectively), while
      those of PCDEs (ng/kg wet weight) were detected in red mullet (7088) followed by
      sardine (1829), anchovy (1606), tuna (1292), and mackerel (1031). For a standard
      male adult, total PBDE and PCDE intakes through edible marine species were 20.8
      and 39.4 ng/ day, respectively. The highest contributions to these intakes
      (ng/day) corresponded to the consumption of tuna (5.7), salmon (3.6), and hake
      (3.5) for PBDEs, and tuna (13.1), hake (7.3), and sardine (6.9) for PCDEs.
      Although currently there is not evidence of the dioxin-like behavior of PBDEs,
      further research is necessary to assess if long-term exposure to PBDEs, mainly
      through the diet, may mean adverse effects to humans. With respectto PCDE
      congeners, to establish TEF values would be of great value to evaluate human
      health risks.

PMID- 16903277
TI  - Occurrence of polybrominated biphenyls, polybrominated dibenzo-p-dioxins, and
      polybrominated dibenzofurans as impurities in commercial polybrominated diphenyl
      ether mixtures.
AB  - The objective of this study was to determine the concentrations and compositions
      of polybrominated biphenyls (PBBs), polybrominated dibenzo-p-dioxins (PBDDs), and
      polybrominated dibenzofurans (PBDFs) as contaminants in the commercial
      polybrominated diphenyl ether (PBDE) mixtures DE-71, DE-79, and DE-83 and to
      ascertain the lot-to-lot variations in the proportions of these contaminants.
      Commercial PBDE mixtures tested in the present study contained both PBBs and
      PBDFs, as impurities, at concentrations in the range of several tens to several
      thousands of nanograms per gram. Concentrations of total PBDFs were greater than
      those of total PBBs in DE-79 and DE-83 mixtures. PBDDs were not detected at
      levels above the limit of detection. Profiles of PBB and PBDF congeners varied
      with the degree of bromination of the commercial PBDE mixtures (i.e., more highly
      brominated mixtures of PBDEs contained heavily brominated homologues of PBBs and
      PBDFs). On the basis of the production/ usage of commercial PBDE mixtures in
      2001, potential global annual emissions of PBBs and PBDFs were calculated to be
      40 and 2300 kg, respectively. Results of our study suggestthat PBDFs can also be
      formed during the production of commercial PBDE mixtures, in addition to their
      formation during pyrolysis of brominated flame retardants.

PMID- 16903278
TI  - Hydrocarbon emissions from in-use commercial aircraft during airport operations.
AB  - The emissions of selected hydrocarbons from in-use commercial aircraft at a major
      airport in the United States were characterized using proton-transfer reaction
      mass spectrometry (PTR-MS) and tunable infrared differential absorption
      spectroscopy (TILDAS) to probe the composition of diluted exhaust plumes
      downwind. The emission indices for formaldehyde, acetaldehyde, benzene, and
      toluene, as well as other hydrocarbon species, were determined through analysis
      of 45 intercepted plumes identified as being associated with specific aircraft.
      As would have been predicted for high bypass turbine engines, the hydrocarbon
      emission index was greater in idle and taxiway acceleration plumes relative to
      approach and takeoff plumes. The opposite was seen in total NOy emission index,
      which increased from idle to takeoff. Within the idle plumes sampled in this
      study, the median emission index for formaldehyde was 1.1 g of HCHO per kg of
      fuel. For the subset of hydrocarbons measured in this work, the idle emissions
      levels relative to formaldehyde agree well with those of previous studies. The
      projected total unburned hydrocarbons (UHC) deduced from the range of in-use idle
      plumes analyzed in this work is greater than a plausible range of engine types
      using the defined idle condition (7% of rated engine thrust) in the International
      Civil Aviation Organization (ICAO) databank reference.

PMID- 16903279
TI  - Seasonal variability and long term trends of chlorofluorocarbon mixing ratios in
      the unsaturated zone.
AB  - To investigate processes that might affect chlorofluorocarbon (CFC) mixing ratios
      at the water table, a time series was obtained of unsaturated zone soil gas CFCs
      to depths of ca. 4 m at a site near New York City (NYC). Observed CFC 11, 12, and
      113 mixing ratios were lower in winter than expected from either a local, high
      resolution time series or remote atmospheric mixing ratios. A diffusion model,
      which includes seasonal changes in soil temperature, moisture, and CFC
      solubility, reproduces to first order the observed soil gas mixing ratios for CFC
      11 and 12. Underestimation by the model of the seasonal cycle of CFC 11 points to
      changing levels of sorption to soils due to seasonal changes in temperature as an
      additional cause of the cycle seen in CFC 11 mixing ratios in soil air. In the
      case of spring recharge, low CFC mixing ratios in soil air caused by increased
      solubility may result in low CFC 11 concentrations in groundwater and, when
      dating groundwater recharged before the 1990s with CFCs, older apparent ages by
      up to 4 years. Attempts to observe average atmospheric CFC levels from soil gas
      are also significantly hindered by these seasonal fluctuations. Our results
      indicate the importance of considering seasonal changes in soil temperature when
      making precise observations of even very moderately soluble gases in the
      unsaturated zone and shallow groundwater.

PMID- 16903280
TI  - Indoor secondary pollutants from household product emissions in the presence of
      ozone: A bench-scale chamber study.
AB  - Ozone-driven chemistry is a source of indoor secondary pollutants of potential
      health concern. This study investigates secondary air pollutants formed from
      reactions between constituents of household products and ozone. Gas-phase product
      emissions were introduced along with ozone at constant rates into a 198-L Teflon
      lined reaction chamber. Gas-phase concentrations of reactive terpenoids and
      oxidation products were measured. Formaldehyde was a predominant oxidation
      byproduct for the three studied products, with yields for most conditions of 20
      30% with respect to ozone consumed. Acetaldehyde, acetone, glycolaldehyde, formic
      acid, and acetic acid were each also detected for two or three of the products.
      Immediately upon mixing of reactants, a scanning mobility particle sizer detected
      particle nucleation events that were followed by a significant degree of
      secondary particle growth. The production of secondary gaseous pollutants and
      particles depended primarily on the ozone level and was influenced by other
      parameters such as the air-exchange rate. Hydroxyl radical concentrations in the
      range 0.04-200 x 10(5) molecules cm(-3) were determined by an indirect method. OH
      concentrations were observed to vary strongly with residual ozone level in the
      chamber, which was in the range 1-25 ppb, as is consistent with expectations from
      a simplified kinetic model. In a separate chamber study, we exposed the dry
      residue of two products to ozone and observed the formation of gas-phase and
      particle-phase secondary oxidation products.

PMID- 16903281
TI  - Microbial reductive debromination of polybrominated diphenyl ethers (PBDEs).
AB  - Polybrominated diphenyl ethers (PBDEs) are a class of widely used flame
      retardants that have recently been detected in environmental samples, diverse
      biota, human blood serum, and breast milk at exponentially increasing
      concentrations. Currently, little is known about the fate of these compounds, and
      in particular, about the microbial potential to degrade them. In this study,
      debromination of deca-BDE and an octa-BDE mixture is demonstrated with anaerobic
      bacteria including Sulfurospirillum multivorans and Dehalococcoides species.
      Hepta- and octa-BDEs were produced by the S. multivorans culture when it was
      exposed to deca-BDE, although no debromination was observed with the octa-BDE
      mixture. In contrast, a variety of hepta- through di-BDEs were produced by
      Dehalococcoides-containing cultures exposed to an octa-BDE mixture, despite the
      fact that none of these cultures could debrominate deca-BDE. The more toxic hexa
      154, penta-99, tetra-49, and tetra-47 were identified among the debromination
      products. Because the penta-BDE congeners are among the most toxic PBDEs,
      debromination of the higher congeners to more toxic products in the environment
      could have profound implications for public health and for the regulation of
      these compounds.

PMID- 16903282
TI  - Flow fingerprinting fecal pollution and suspended solids in stormwater runoff
      from an urban coastal watershed.
AB  - Field studies were conducted to characterize the concentration vs streamflow
      relationships (or "flow fingerprints") of fecal pollution and suspended solids in
      stormwater runoff from the Santa Ana River watershed, the largest watershed in
      southern California. The concentrations of fecal indicator bacteria and F+
      coliphages (viruses infecting E. coli) exhibit little-to-no dependence on
      streamflow rates, whereas the concentrations of total suspended solids (TSS)
      exhibit a very strong (power-law) dependence on streamflow rates. The different
      flow fingerprints observed for fecal pollutants, on one hand, and TSS, on the
      other hand, reflect different sources and transport pathways for these stormwater
      constituents. The flow-independent nature of fecal indicator bacteria and F+
      coliphages is consistent with the idea that these contaminants are ubiquitously
      present on the surface of the urban landscape and rapidly partition into the
      surface water as the landscape is wetted by rainfall. The flow-dependent nature
      of TSS, on the other hand, is usually ascribed to the shear-induced erosion of
      channel bed sediments and/or the expansion of drainage area contributing to
      runoff. The apparent ubiquity of fecal indicator bacteria and F+ coliphages,
      together with the very high storm-loading rates of fecal indicator bacteria and
      the low detection frequency of human adenovirus and human enterovirus, suggest
      that fecal pollution in stormwater runoff from the Santa Ana River watershed is
      primarily of nonhuman waste origin.

PMID- 16903283
TI  - The inhibitory effects of free nitrous acid on the energy generation and growth
      processes of an enriched nitrobacter culture.
AB  - The inhibitory effects of nitrite (NO2-)/free nitrous acid (HNO2-FNA) on the
      metabolism of Nitrobacter were investigated using a method allowing the
      decoupling of the growth and energy generation processes. A lab-scale sequencing
      batch reactor was operated forthe enrichment of a Nitrobacter culture.
      Fluorescent in situ hybridization (FISH) analysis showed that 73% of the
      bacterial population was Nitrobacter. Batch tests were carried out to assess the
      oxygen and nitrite consumption rates of the enriched culture at low and high
      nitrite levels, in the presence or absence of inorganic carbon. It was observed
      that in the absence of CO2, the Nitrobacter culture was able to oxidize nitrite
      at a rate that is 76% of that in the presence of CO2, with an oxygen consumption
      rate that is 85% of that measured in the presence of CO2. This enabled the
      impacts of nitrite/FNA on the catabolic and anabolic processes of Nitrobacter to
      be assessed separately. FNA rather than nitrite was likely the actual inhibitor
      to the Nitrobacter metabolism. It was revealed that FNA of up to 0.05 mg HNO2-N x
      L(-1) (3.4 microM), which was the highest FNA concentration used in this study,
      did not have any inhibitory effect on the catabolic processes of Nitrobacter.
      However, FNA initiated its inhibition to the anabolic processes of Nitrobacterat
      approximately 0.011 mg HNO2-N x L(-1) (0.8 microM), and completely stopped
      biomass synthesis at a concentration of approximately 0.023 mg HNO2-N x L(-1)
      (1.6 microM). The inhibitory effect could be described by an empirical inhibitory
      model proposed in this paper, but the underlying mechanisms remain to be
      revealed.

PMID- 16903284
TI  - Reduction of nitrosobenzenes and N-hydroxylanilines by Fe(II) species:
      elucidation of the reaction mechanism.
AB  - Although there has been a substantial effort toward understanding the reduction
      of nitroaromatics in Fe(II)-treated ferric oxide systems, little has been done to
      gain insight into the factors controlling the transformation of their reaction
      intermediates, nitrosobenzenes and N-hydroxylanilines, in such systems.
      Nitrosobenzenes, the first intermediates, were reduced by Fe(II) solutions as
      well as by Fe(II)-treated goethite suspensions at pH 6.6. Experimental
      observations indicate a reactivitytrend in which the presence of electron
      withdrawing groups in the para position increased the rate of reduction of the
      nitrosobenzenes. N-Hydroxylanilines, the second intermediates, were reduced in
      Fe(II)-treated goethite suspensions but were not reduced by Fe(II)aq. Their
      reactivity trend indicates that electron-withdrawing groups in the para position
      decreased their rate of reduction. The bond dissociation enthalpy of the N-O
      linkage was the most useful molecular descriptor for predicting the rates of
      reduction of N-hydroxylanilines in Fe(II)-treated goethite suspensions,
      suggesting that the cleavage of the N-O bond is the rate-determining step for
      reduction. The rate of reduction of p-cyano-N-hydroxylaniline showed a linear
      relationship against the concentration of surface-associated Fe(II) in hematite,
      goethite, and lepidocrocite suspensions, while having a relatively low
      sensitivity toward changes in pH within the near-neutral range in hematite
      suspensions.

PMID- 16903285
TI  - Photochemical source of metals for sediments.
AB  - A mass budget study of major in-lake Al fluxes, palaeolimnological data on a
      >10,000 year old sediment record, and in situ photochemical experiments performed
      at Plesne Lake (Czech Republic) suggest that photochemical liberation of
      organically bound aluminum (Al) and iron (Fe) by solar radiation is a significant
      natural source of their ionic species for lakes and subsequent oxyhydroxides for
      sediments. The results show that photochemically induced transformation of
      dissolved Al and Fe to solid oxyhydroxides deposited to Plesne Lake sediment
      dominated (91 and 73%, respectively) their sedimentary flux throughout the
      preindustrial era, since soil formation initiated in the catchment. The following
      sequence of processes occurs: (i) soil organic acids dissolve and bind metals and
      export them from terrestrial to aquatic systems. (ii) Photochemical decomposition
      of organic-metal complexes liberates a significant portion (approximately 50% in
      Plesee Lake) of organically bound Al and Fe as inorganic ions. (iii) The
      liberated ionic Al and Fe hydrolyze, precipitate as oxyhydroxide particles, and
      settle. We hypothesise that the same Al and Fe transporting process occurs in
      other lakes and coastal marine areas and is ecologically important because Al and
      Fe oxyhydroxides can bind trace metals and phosphorus.

PMID- 16903286
TI  - Relative rate constants of contaminant candidate list pesticides with hydroxyl
      radicals.
AB  - The objective of this study was to establish the relative rate constants for the
      reactions of selected pesticides (linuron, diuron, prometon, terbacil, diazinon,
      dyfonate, terbufos, and disulfoton) listed on the U.S. EPA Contaminant Candidate
      Listwith UV and hydroxyl radicals (*OH). Batch experiments were conducted in
      phosphate buffered solution at pH 7. All pesticides were found to be very
      reactive toward *OH as indicated by rate constant values above 10(9) M(-1) s(-1).
      Using molinate as a reference compound, kOH ranged from 2.7 x 10(9) to 12.0 x
      10(9) M(-1) s(-1) for the contaminants while slightly higher values from 2.9 x
      10(9) to 14.3 x 10(9) M(-1) s(-1) were obtained using nitrobenzene as a reference
      compound. A method was established that accounts for direct photolysis when
      calculating kOH using UV/H2O2 process for compounds which degrade significantly
      by a direct photolysis mechanism.

PMID- 16903287
TI  - Kinetics of the microbial reductive dechlorination of pentachloroaniline.
AB  - The microbial reductive dechlorination kinetics of pentachloroaniline (PCA) and
      less chlorinated anilines (CAs) were investigated with a mixed, fermentative/
      methanogenic culture. Batch dechlorination assays were performed with all
      available CAs at an initial concentration of 3 microM, and an incubation
      temperature of 22 degrees C. Dechlorination of PCA, two tetrachloroanilines
      (2,3,4,5- and 2,3,5,6-TeCA), five trichloroanilines (2,3,4-, 2,3,5-, 2,4,5-,
      2,4,6-, and 3,4,5-TrCA), and one dichloroaniline (3,5-DCA; low extent) was
      observed but none of the five remaining dichloroanilines and three
      monochloroanilines were dechlorinated by the enrichment culture during batch
      assays. The dechlorination rates (k') and half-saturation coefficients (Kc) were
      measured using nonlinear regression based on the integrated Michaelis-Menten
      equation under conditions of electron donor saturation and assuming constant
      biomass concentration over the relatively short batch incubation period. At an
      initial concentration of CAs of about 3 microM, the values of k' and Kc ranged
      from 0.25 to 1.19 microM/day and from 0.11 to 1.72 microM, respectively,
      corresponding to half-lives in the range of 1.5-8.5 days. Model simulations of
      the sequential dechlorination reactions based on a branched-chain Michaelis
      Menten model and using independently measured k' and Kc values matched the
      experimental data very well.

PMID- 16903288
TI  - A modeling study and implications of competition between Dehalococcoides
      ethenogenes and other tetrachloroethene-respiring bacteria.
AB  - Bioaugmentation with cultures containing Dehalococcoides strains that
      dechlorinate cis-1,2-dichloroethene (cDCE) to ethene is often recommended at
      sites where indigenous populations dechlorinate tetrachloroethene (PCE) to cDCE.
      In these cases, Dehalococcoides populations may have to compete with other
      dehalorespirers for chlorinated ethenes and/or electron donors. A continuous-flow
      stirred tank reactor model was used to describe the substrate interactions in
      three conceptual models of competition between PCE-respiring populations under
      natural attenuation and engineered bioremediation scenarios. Model simulations
      were used to evaluate the effects of other chlorinated ethene respirers on
      substrate utilization by, and growth of, a Dehalococcoides strain (Dhc.
      ethenogenes strain 195) and identify the key factors influencing the outcome of
      competition among different dehalorespirers. The results suggest that, under
      natural attenuation conditions, Dhc. ethenogenes is unlikely to be the dominant
      population if a dehalorespirer that can compete for limiting amounts of reducing
      equivalents is present. Engineered bioremediation conditions resulted in greater
      enrichment of Dhc. ethenogenes than of competing dehalorespirers. Under several
      conditions, Dhc. ethenogenes coexisted with a PCE-to-cDCE (or PCE-to-TCE)
      dehalorespirer, primarily by functioning as a cDCE- (or TCE)-to-ethene
      dechlorinating specialist. From a bioremediation standpoint, maintenance of
      multiple dehalorespiring specialists appears ideal because it may result in the
      fastest and most extensive chlorinated ethene transformations. Thus, to improve
      our ability to successfully implement bioremediation, it may be helpful to
      characterize the indigenous PCE-to-cDCE respiring populations and the nature and
      distribution of electron donors used by these dehalorespirers at contaminated
      sites. Further understanding of these interactions requires more accurate
      information on the kinetics of known dehalorespiring populations.

PMID- 16903289
TI  - Effect of accelerated aging of MSWI bottom ash on the leaching mechanisms of
      copper and molybdenum.
AB  - The effect of accelerated aging of Municipal Solid Waste Incinerator (MSWI)
      bottom ash on the leaching of Cu and Mo was studied using a "multisurface"
      modeling approach, based on surface complexation to iron/aluminum (hydr)oxides,
      mineral dissolution/precipitation, and metal complexation by humic substances. A
      novel experimental method allowed us to identify that the solid/liquid
      partitioning of fulvic acids (FA) quantitatively explains the observed beneficial
      effect of accelerated aging on the leaching of Cu. Our results suggestthat
      iron/aluminum (hydr)oxides are the major reactive surfaces that retain fulvic
      acid in the bottom ash matrix, of which the aluminum (hydr)oxides were found to
      increase after aging. A new modeling approach, based on the surface complexation
      of FA on iron/aluminum (hydr)oxides is developed to describe the pH-dependent
      leaching of FA from MSWI bottom ash. Accelerated aging results in enhanced
      adsorption of FA to (neoformed) iron/aluminum (hydr)oxides, leading to a
      significant decrease in the leaching of FA and associated Cu. Accelerated aging
      was also found to reduce the leaching of Mo, which is also attributed to enhanced
      adsorption to (neoformed) iron/aluminum (hydr)oxides. These findings provide
      important new insights that may help to improve accelerated aging technology.

PMID- 16903290
TI  - Reaction mechanism and kinetic modeling of DEET degradation by flow-through
      anodic fenton treatment (FAFT).
AB  - The previously developed batch anodic Fenton treatment (AFT) technology has been
      successfully applied to degrade various pesticides in aqueous solution. The goal
      of this work is the development of a flow-through AFT system (FAFT) which is
      critical to bringing this technology into practical general use in the field. For
      this purpose, the degradation of DEET (N,N-diethyl-3-methylbenzamide), an insect
      repellent, and nine model amides was studied. Oxidation products of these
      compounds in FAFT were identified by GC/MS, and the results revealed that various
      -OH additions (most likely on the aromatic ring), quinone/keto product formation,
      and dimerization/bimolecular disproportionation are the major reaction pathways.
      This proposed overall reaction mechanism was then combined with the basic
      Fenton's mechanism to model the kinetics of various active species in FAFT
      including DEET, Fe2+, H2O2, and total iron under different reaction conditions.
      In addition, both initial and steady-state hydroxyl radical concentrations were
      measured in FAFT using benzoic acid as a chemical probe; the measured *OH
      concentrations were best-fitted exponentially. On the basis of the obtained [*OH]
      trend and the mass balance of the FAFT system, a simple FAFT model was developed
      to fit all of the degradation data of DEET and the model amides.

PMID- 16903291
TI  - Understanding the size and character of fouling-causing substances from effluent
      organic matter (EfOM) in low-pressure membrane filtration.
AB  - Stirred cell tests with microfiltration (MF) and ultrafiltration (UF) membranes
      show high flux decline for WWTP effluents. For the MF membrane, for example, the
      flux declines within 15 min to 70-80% of the initial flux (J0 is in the range of
      1000 L/m2h to 1500 L/m2h). This time corresponds to the filtration of a
      cumulative volume of 110 L/m2. Feed and permeate samples of the stirred cell
      tests are analyzed by size-exclusion chromatography (SEC) with on-line organic
      carbon and UVA254 detection. The resulting chromatograms exhibit a clear
      difference between the feed and permeate samples in the so-called polysaccharide
      (PS) peak. The substances eluting in the PS peak (organic colloids,
      polysaccharides, and proteins) are retained completely by UF membranes and partly
      by MF membranes, and are responsible for the observed fouling. By sequential
      filtration experiments the sizes of these macromolecules are determined to be in
      the range of 10 to 100 nm.

PMID- 16903292
TI  - Use of illite clay for in situ remediation of 137Cs-contaminated water bodies:
      field demonstration of reduced biological uptake.
AB  - We hypothesized that adding micaceous minerals to 137Cs-contaminated aquatic
      systems would serve as an effective in situ remediation technique by sequestering
      the contaminant and reducing its bioavailability. Results from several laboratory
      studies are presented from which an effective amendment material was chosen for a
      replicated field study. The field study was conducted over a 2-year period and
      incorporated 16 3.3-m diameter column-plots (limnocorrals) that were randomly
      placed in a 137Cs-contaminated pond. The limnocorrals received three rates of
      amendment treatments to their water surfaces. The amendment material was a
      commercially available mineral with high sorption (Kd > 9000 L kg(-1)) and low
      desorption (<20%) characteristics for cesium, even in the presence of high
      concentrations of the competing cation, NH4+. In the treated limnocorrals, 137Cs
      concentrations were reduced some 25-30-fold in the water, 4-5-fold in aquatic
      plants, and 2-3-fold in fish. The addition of the amendment did not adversely
      affect water chemistry, although increased turbidity and subsequent siltation did
      alter the aquatic macroinvertebrate insect community. This in situ technology
      provides a valuable, less-environmentally intrusive alternative to costly ex situ
      technologies that require the contaminated sediment to be excavated prior to
      treatment, or excavated and disposed of elsewhere.

PMID- 16903293
TI  - Operational sustainability metrics assessing metric effectiveness in the context
      of electronics-recycling systems.
AB  - In the past 15 years corporations and governments have developed a growing
      appreciation of the need for sustainability. However, there is still little
      clarity on how to move toward the goal of sustainability or measure improvements.
      Not only are there currently few operational metrics by which to practically
      assess progress toward sustainability, there is also little understanding of how
      to judge the effectiveness of such metrics. This paper presents a pragmatic
      approach to developing--and evaluating--system-specific performance metrics for
      sustainability. Electronics recycling is used as a case problem in developing and
      judging the effectiveness of such metrics. Despite growing concerns aboutthe
      handling of end-of-life electronics, data availability is inconsistent, and there
      is still limited understanding of the electronics-recycling system as a whole. To
      begin to address the need for practical quantitative methods to assess system
      performance, several indicators were developed and applied to three U.S.
      electronics-recycling operations. These metrics were assessed based on the
      developed criteria that effective measures be useful, robust, and feasible.
      Results show that the current measure of "mass percent to landfill" is not
      sufficient to assess system performance. Relevance-weighted mass indicators with
      varying data requirements can provide additional insights on resource efficiency.

PMID- 16903294
TI  - Bioavailability models for predicting copper toxicity to freshwater green
      microalgae as a function of water chemistry.
AB  - We investigated whether an earlier-developed bioavailability model for predicting
      copper toxicity to growth rate of the freshwater alga Pseudokirchneriella
      subcapitata could be extrapolated to other species and toxicological effects
      (endpoints). Hardness and dissolved organic carbon did not significantly affect
      the toxicity of the free Cu2+ ion to P. subcapitata (earlier study) and Chlorella
      vulgaris(this study), but a higher pH resulted in an increased toxicity for both
      species. Regression analysis showed significant linear relationships between
      ECxpCu (= "effect concentration" that produces x% adverse effect, expressed as
      pCu = -log of the Cu2+ activity) and pH. By linking these regression models with
      a geochemical metal speciation model, dissolved copper concentrations that elicit
      a given adverse effect (EC(X)dissolved) can be predicted. Within the pH range
      investigated (5.5-8.7), slopes of the linear EC(X)pCu vs pH regression models
      varied between 1.301 and 1.472 depending on the species and the effect level (10%
      or 50%) considered. In a statistical sense these slopes were all significantly
      different from one another (p < 0.05), suggesting that this empirical regression
      model does not yet capture the full complexity of toxicological copper
      bioavailability to algae. However, we demonstrated that regression models with an
      "average" slope of 1.354 had predictive power very similar to those of regression
      models with species and effect-specific slopes. Additionally, the "average"
      regression model was further successfully validated for other species
      (Chlamydomonas reinhardtii and Scenedesmus quadricauda) and for different
      toxicological effects/endpoints (growth rate, biomass yield, and phosphorus
      uptake rate). For all these toxicity datasets effect concentrations of copper
      could be predicted with this "average" model by errors of less than a factor of 2
      in 94-100% of the cases. The success of this "average" model suggests the
      possibility that the pH-based linear regression model may form a sound conceptual
      basis for modeling the toxicological bioavailability of copper to green algae in
      regulatory assessments, although a full mechanistic understanding is lacking and
      should be the focus of future studies.

PMID- 16903295
TI  - Co-transport of metal complexes by the green mussel Perna viridis.
AB  - We examined the uptake of ligand-bound metals (Cd and Zn) by the green mussel
      Perna viridis using defined artificial seawater. Different free ion
      concentrations (1 pM to 10 microM) in uptake solutions were created by adding
      different amounts of total metals (Cd 0.1 nM to 0.1 mM; Zn 0.5 nM to 0.05 mM) and
      ligands (EDTA, NTA, citric acid). Our results showed that Cd and Zn uptake could
      not be fully explained by the free Cd and Zn concentrations in the presence of
      different ligands, indicating that metal-ligand complexes were at least partially
      available for uptake by the mussels. Total Zn concentrations appeared to be a
      better predictor of metal uptake than the free Zn ion concentrations in the
      presence of different ligands. Uptake of lipophilic organic metal complexes was
      substantially greater than the hydrophilic metal complexes, even though the free
      ion concentration was comparable or lower. Moreover, the radiolabeled ligand
      compounds were directly accumulated by the mussels. The accumulation of metal
      complexes may explain the increased metal uptake with increasing ligand and total
      metal concentration, even though the free ion metal concentration was constant.
      Overall, our experimental results indicated that free metal ion cannot fully
      explain metal uptake since metal complex species were also available to the
      mussels to some extent, apparently through a co-transport process.

PMID- 16903296
TI  - Nurses face tougher regulation.

PMID- 16903297
TI  - Children have a right to protection from preventable diseases.

PMID- 16903298
TI  - Gaps in the training picture.

PMID- 16903299
TI  - Helping nurses kick the habit.

PMID- 16903300
TI  - Joint working has many benefits.

PMID- 16903301
TI  - Promoting sexual health to young people to reduce STIs.
AB  - Despite sexual health remaining virtually non-existent in most pre-registration
      curricula, preventative healthcare is an obligation in the NMC's (2004) Code of
      Professional Conduct. Promoting effective condom use, as a proven contra
      infection healthcare resource, over and above its contraceptive potential, is an
      essential element of good holistic care and is a key concept of health promotion
      and duty of care.

PMID- 16903302
TI  - Air embolism.

PMID- 16903303
TI  - Resuscitation skills - part six: synchronised electrical cardioversion.

PMID- 16903304
TI  - An overview of acne vulgaris.
AB  - Acne vulgaris (common acne) is the most common disease seen by dermatologists
      (Lookingbill and Marks, 2000). It is a chronic inflammatory condition of the
      pilosebaceous units (Oprica et al, 2002) and with therapy the prognosis is good.

PMID- 16903305
TI  - Use of study days to develop the healthcare assistant role.
AB  - The Department of Health's strategies to combat staff shortages and an ageing
      workforce have now turned their focus to the delivery of patient care by HCAs.
      This article describes how a trust redesigned the role of HCAs and implemented a
      study day in order to enhance both theoretical knowledge and clinical practice
      for this role.

PMID- 16903306
TI  - Taxanes.

PMID- 16903307
TI  - Building partnerships for the improvement of public health.
AB  - The UK has seen an increase in initiatives to encourage partnership working with
      the aim of improving services to patients and communities. This article looks at
      inter-organisational and interprofessional relationships for the improvement of
      public health. It highlights the importance of collaborative working and looks at
      how to identify possible partners and ensure coordination.

PMID- 16903309
TI  - Principles of resuscitation in primary care.

PMID- 16903310
TI  - A campaign to encourage hand hygiene in schools.

PMID- 16903311
TI  - Meeting the psychosocial challenges of leg ulceration.

PMID- 16903312
TI  - Practical management of infant food allergies.

PMID- 16903313
TI  - Adverse drug reactions.

PMID- 16903315
TI  - UV dependence.

PMID- 16903316
TI  - What is your diagnosis? Cowden disease (multiple hamartoma syndrome).

PMID- 16903317
TI  - Aquatic antagonists: sea anemone dermatitis.

PMID- 16903318
TI  - Generalized atrophic dells in a newborn.
AB  - Infantile myofibromatosis (IM) is a nonmetastasizing locally invasive neoplasm.
      The behavior of the tumor is more hamartomatous than tumoral, and it is unclear
      whether the cell of origin is a fibroblast or a smooth muscle myocyte. Lesions
      typically present during infancy and range in size from a few millimeters to
      several centimeters. We present an unusual case of a patient with an atrophic
      variant of IM.

PMID- 16903319
TI  - Malignant acanthosis nigricans and tripe palms associated with pancreatic
      adenocarcinoma.
AB  - Malignant acanthosis nigricans is a disease that has an abrupt onset and is most
      commonly associated with gastric adenocarcinoma. It also has occurred as a
      paraneoplastic phenomenon in other carcinomas. Malignant acanthosis nigricans can
      occur simultaneously, before, or after the onset of internal malignancy.
      Malignant acanthosis on the palms is referred to as tripe palms. We describe a
      rare association of oral malignant acanthosis nigricans and tripe palms secondary
      to an underlying pancreatic adenocarcinoma.

PMID- 16903320
TI  - Hereditary basaloid follicular hamartoma syndrome.
AB  - Basaloid follicular hamartoma syndrome (BFHS) is a rare adnexal tumor
      genodermatosis. We present a case of hereditary BFHS and review the literature
      concerning the clinical and histologic features of this entity.

PMID- 16903321
TI  - Cutaneous cryptococcus in an elderly woman with chronic essential dermatitis.
AB  - Cryptococcus neoformans is a common cause of life-threatening infection.
      Cutaneous manifestations of Cryptococcus can be primary or secondary, most
      commonly from immunosuppression. With the global emergence of acquired
      immunodeficiency syndrome (AIDS), incidence of cryptococcosis is increasing and
      now represents a major life-threatening fungal infection in these patients.
      Nonspecific lesions may cause misdiagnosis. Disseminated Cryptocoocus requires
      early clinical diagnosis and effective management to decrease mortality. We
      review a case of cutaneous Cryptococcus as a complication of chronic essential
      dermatitis treated with long-term immunosuppressive agents and discuss updated
      guidelines on the treatment of Cryptococcus.

PMID- 16903322
TI  - Chronic mucocutaneous candidiasis associated with malignant thymoma and systemic
      lupus erythematosus with hypergammaglobulinemia: a case report and literature
      review.
AB  - Chronic mucocutaneous candidiasis (CMC) is characterized by recurrent candidal
      infections of the mucous membranes, nails, and skin. Systemic involvement is
      rare. CMC in adults with coexistent thymoma, benign or malignant, is well-known
      and is often associated with hypogammaglobulinemia. There is an unusually high
      frequency of thymoma and systemic lupus erythematosus (SLE). I present a case of
      a patient with a history of malignant thymoma, SLE, and hypergammaglobulinemia
      who was found to have CMC. Discussion of the relationship of these findings is
      presented.

PMID- 16903323
TI  - Sjogren-Larsson syndrome: a case report and literature review.
AB  - Sjogren-Larsson syndrome (SLS) is an autosomal recessive neurocutaneous disorder
      most commonly seen in the Scandinavian population and characterized by congenital
      ichthyosis, mental retardation, and spastic diplegia or quadriplegia. We report a
      case of SLS in an 11-month-old girl of Lebanese and Mexican-Syrian ancestry who
      presented with ichthyosis, developmental delay, and spasticity. Results of an
      enzymatic assay and genomic DNA testing in cultured skin fibroblasts confirmed a
      homozygous C237Y mutation. These findings support the rich diversity of mutations
      associated with this syndrome.

PMID- 16903324
TI  - Resolution of tinea pedis with imiquimod cream 5% in a patient with nodular basal
      cell carcinoma.
AB  - A 73-year-old white man with nodular basal cell carcinoma (nBCC) of the toe and
      interdigital tinea pedis was treated with imiquimod cream 5% once daily for 4
      weeks and twice daily for 10 weeks. Results of a posttreatment potassium
      hydroxide (KOH) preparation and biopsy confirmed clearance of both tinea pedis
      and nBCC, respectively.

PMID- 16903325
TI  - [Analysis of complications after surgical voice and speech rehabilitation in
      laryngectomized patients. Problems related to implantation and change of voice
      prosthesis].
AB  - INTRODUCTION: Surgical rehabilitation of voice and speech, with implantation of
      Provox 2 voice prosthesis is becoming a standard procedure in Poland in the last
      few years. Still some opinions are raised, considering the potential risk of
      complications, particularly, when tracheo-esophageal puncture is finally located
      in the irradiated tissue. AIM OF THE STUDY: The assessment of safety, and
      analysis of complication encountered with tracheo-esophageal puncture, and
      implantation of voice prosthesis. MATERIAL AND METHOD: The 106 cases of patients
      treated with mentioned above method. The primary implantation was performed in 73
      (68,9%) cases; the secondary implantation in 33 (31,1%). The 85 (80,2%) patients
      received radiotherapy before, or after implantation. In the analyzed period (2002
      2004) apart of 106 implantations, the replacement of 132 prostheses was
      performed. RESULTS: There was only one, potentially life-threatening complication
      recorded in the analyzed group of 106 patients--inhalation of prosthesis to
      tracheo-bronchial tree. The most common complications directly related to
      implantation were: infection in the place of created fistula after secondary
      implantation 4/33(12,1%), and spontaneous partial extrusion of prosthesis with
      occlusion of created fistula tract 8/106 (7,5%). The average lifetime of
      prosthesis in place, was 9,8 months in irradiated field, and 9,7 months in
      patients who did not received radiotherapy. CONCLUSIONS: Surgical rehabilitation
      of voice and speech, with implantation of vocal prosthesis is safe and reliable
      procedure. The radiotherapy applied before or after creation of tracheo
      esophageal fistula is not a contra indication for this method. Generally low rate
      of complications is similar in both groups--who does received or not received
      radiotherapy. Also the stability of implanted prostheses were similar in both
      groups.

PMID- 16903326
TI  - [Tumors infiltrating carotid artery--diagnostic and principles of treatment].
AB  - The involvement of internal or common carotid artery by neoplasmatic process
      usually indicates advanced stage of a disease and is always a serious problem for
      surgical treatment. The high risk of surgical and neurological complications,
      frequent local reappearance, distant metastases and significant loss of quality
      of life should have influence on mode of scheduled treatment. Current options of
      diagnosis and treatment with special focus on surgical carotid artery
      reconstruction are presented based on the review of the articles related to this
      problem. Our 3-years experience with this group of patients is presented.

PMID- 16903327
TI  - [Multiple bilateral lymphatic adenomas of the parotid glands].
AB  - INTRODUCTION: Multiple primary tumours of the parotid glands are very rare. They
      may occur unilaterally or bilaterally, synchronously or metachronously. Whartin's
      tumour is mostly find in bilateral parotid gland tumours. MATERIAL AND METHODS:
      The authors present an unusual case of 60 years old man with bilateral,
      multifocal Whartin's tumour of the parotid glands. The tumours have appeared
      synchronously two years before the diagnosis was done. We performed bilateral
      superficial partial parotidectomy with removal of the tumours. RESULTS AND
      CONCLUSION: The multifocal, synchronous bilateral Whartin's tumours of the
      parotid glands are very rare. Minimal surgery procedures with tumour excision is
      the method of choice. The recurrence rate is very low.

PMID- 16903328
TI  - [RANTES expression in nasal polyps fibroblasts; spontaneously and after
      stimulation with lipopolisaccharides (LPS) and phytohemagglutinin (PHA)].
AB  - INTRODUCTION: According to the results of research carried out by a number of
      authors, one of the main mechanisms of the generation of polyps is local
      inflammatory processes accompanied by immune system disorders. It has recently
      been shown that a number of differentiation factors and inflammatory mediators
      may be involved in the growth of nasal polyps. RANTES is a eosinophil
      chemoattractant factor likely could play an important role in a chronic
      inflammatory response in the nasal tissue that subsequently leads to the
      development of nasal polyps. OBJECTIVE: The objective of this study was detection
      of the chemokine RANTES in nasal polyps fibroblasts and researching influence of
      stimulation with lipopolisaccharides and phytohemagglutinin for RANTES expression
      in cultured nasal fibroblasts in vitro. METHODS: Nasal polyps were obtained from
      17 subjects (9 atopic and 8 nonatopic) during polypectomy. RANTES was measured by
      immunofluorescence method. RESULTS: Intensive granular luminescence was observed
      in all cytoplasm of cells with the exception of nucleus. Immunoreactive RANTES
      was found to be present in 70% of cells. We not find increase percentage of
      positive RANTES fibroblasts after stimulation with lipopolisaccharides and
      phytohemagglutinin. RANTES expression was similar in the both: atopic and
      nonatopic polyps. CONCLUSIONS: This study demonstrates that cultured fibroblasts
      derived from both atopic and nonatopic patients release RANTES spontaneously and
      after stimulation with lipopolisaccharides and phytohemagglutinin. This
      observation and the finding that RANTES is present in nasal polyps fibroblasts
      suggest that this chemokine may be an important mediator of eosinophil in both
      atopic and nonatopic nasal polyposis. More research needs to expand on
      chemotactic factors such as RANTES and their interplay with other local
      cytokines.

PMID- 16903329
TI  - [Stomal recurrence after total laryngectomy].
AB  - Stomal recurrence after total laryngectomy is a very serious complication, in
      general with dismal prognosis. There are only a few possibilities of treatment,
      so stress should be put on prevention. MATERIAL: In the ENT Department Poznan
      University of Medical Sciences between 1997-2004 829 total laryngectomy were
      performed, because of advanced laryngeal cancer (T3, T4). In this group until may
      2005 37 cases of stomal recurrence were found. AIM: The aim of this study was to
      analyse the group of patients stomal recurrence. RESULTS: Stomal reccurence
      developed in 35 men and 2 women. The age of patients was 43-79 years (mean 59
      years). The time of lasting the symptoms before laryngectomy was 6-12 months
      (mean 8 months). The emergency tracheotomy was performed in 16 patients (43%).
      The time between tracheotomy and laryngectomy was 2 days to 3 weeks (mean 6
      days). The subglottic extension was observed in 24 patients (65%). 19 patients
      (51%) was classified as T3, 18 (49%) as T4. 12 patients (32%) was classified as
      N0, 5 (14%) as N1, 16 (43%) as N2 and 4 (11%) as N3. 4 patients were earlier
      treated because of larynx cancer (2 of them has laser chordectomy and 2 fronto
      lateral laryngectomy). The time between laryngectomy and radiotehrapy was 4-15
      weeks (mean 7 weeks). 22 patients (59%) were classified (due Sisson at al) as
      type I, 12 (32%) type II, 2 (6%) type III and 1 (3%) type IV. The treatment of
      stomal recurrences consisted of surgical resection of tumor, chemiotherapy,
      radiotherapy, brachytherapy or palliative treatment. 34 patients died, 2 are
      presently treated and 1 is near 5 years free of disease after surgical treatment.
      CONCLUSIONS: Patients with stomal recurrences begun primary treatment in locally
      and regionally advanced disease. In more that 60% of patients subglottic
      extension was observed. Emergency tracheotomy may predispose to stomal
      recurrence. Limited possibilities of treatment of stomal recurrences are the
      reason of very poor prognosis in this group of patients. During total
      laryngectomy paratracheal lymphatic nodes should be looked for and dissect.

PMID- 16903330
TI  - [Expression of adhesive molecules, angiogenesis markers and protein products of
      suppressor genes in neoplasms of oral cavity and maxillary sinus].
AB  - INTRODUCTION: Adhesion molecules, angiogenesis markers and protein products of
      suppressor genes are potential prognostic indicators in different type of
      tumours. The purpose of this study was to analyze relations between expression of
      these markers and clinical as well as histological features of oral cavity and
      maxillary sinus tumours. MATERIAL AND METHODS: Measurements of expression of
      CD44, TP53, Nm23 oncoproteins and angiogenesis markers were performed. Forty
      three patients treated in years 1985-2000 in the Department of Maxillofacial
      Surgery of the University Hospital in Wroclaw entered our study. Thirty-two of
      them were treated for oral cavity cancers. Remaining eleven patients were treated
      for maxillary sinus cancers. RESULTS: We have shown, there was a positive
      correlation between the number of the vessels and presence of the nodal
      metastases; between histological grading and VCAM expression; between CD44
      expression and total surface area of the blood vessels. There was also
      correlation between total surface area of the blood vessels and patients'
      survival time.

PMID- 16903332
TI  - [Pyocele of the posterior ethmoidal cell as the cause of visual loss].
AB  - INTRODUCTION: Mucocele is a cystic slow-growing lesion of paranasal sinuses with
      sterile content. Pyocele contains purulent substance. Muco-/pyocele is rarely
      localised in ethmoid or sphenoid sinus and may involve the orbit and cause
      ophthalmic complications including visual loss. MATERIAL AND METHODS: We report
      the case of a 25-year-old woman who suffered from sudden visual loss of her left
      eye. She was treated for optic nerve papillitis by neurologists and
      ophthalmologists with steroids and recovered after about 6 weeks. Magnetic
      resonance imaging was ordered to find the cause of visual disturbance and
      revealed an oval-shaped lesion in the left posterior ethmoid sinus. The patient
      underwent functional endoscopic surgery and transethmoidal marsupialisation of
      the muco-/pyocele. RESULTS: After endoscopic microsurgery the patient recovered
      without complications, she is under follow-up and has no symptoms of any disease.
      Because there were no evidence of any other causes of optic nerve affection, the
      muco-/pyocele was regarded as the cause of visual loss. CONCLUSIONS: The
      posterior ethmoid muco-/pyocele can present with ophthalmic manifestations
      including blindness. Endonasal operation and steroids administration are the
      treatment of choice in such cases.

PMID- 16903331
TI  - [Complications in surgical treatment of thyroid diseases].
AB  - THE AIM: of this study was examination of laryngeal nerve injury,
      hypoparathyroidism, bleeding and thyroid storm frequency after thyroidectomy.
      MATERIAL AND METHODS: Retrospective analysis of 847 patients surgically treated
      from 1985 to 2004 due to thyroid cancer (77) or multinodular goiter (770). We
      analyzed influence of type of thyroidectomy, diagnosis and reoperation on
      complication rates. Statistical analysis was performed with Chi2 or Fisher exact
      test. RESULTS: Unilateral lobectomy was performed in 195 cases (23%)--total
      unilateral lobectomy in 51% of patients and partial or subtotal lobectomy in rest
      of them. Bilateral lobectomy was performed in 652 patients--in 20% of cases it
      was total thyroidectomy and partial or subtotal thyroidectomy in 524 of patients.
      There was no mortality in operative or postoperative period. Wound exploration
      due to bleeding was performed in 3 cases (0,4%) and thyroid storm was noticed in
      1,6% of all patients. Unilateral permanent laryngeal nerve injury was in 2,1% of
      patients, in one patient it was permanent bilateral nerve injury and unilateral
      temporary nerve injury in 3,2%. We noticed statistically significant differences
      in permanent and temporary nerve injury between total and partial thyroidectomy
      groups (7,0% vs 1,3% and 8.6% vs 2,2%; p < 0,005) and after primary operation and
      reoperation groups (8,9% vs 1,7% and 6,7% vs 2,9; p < 0,005). Permanent and
      temporary recurrent laryngeal nerve injury rates after total thyroidectomy due to
      cancer or multinodular goiter were not significant (7,8% vs 5,9% and 9,1% vs
      7,8%; p = 0,72). Temporary hypoparathyroidism was noticed in 34 cases (4%) and
      permanent in one case. Again temporary hypoparathyroidism was significantly
      higher after total thyroidectomy compared to partial (18,0% vs 2,1%; p < 0,005)
      and after reoperation (17,8% vs 3,2%; p < 0,005). There were no differences in
      hypoparathyroidism rates after total thyroidectomy due to cancer or multinodular
      goiter (20,8% vs 13,7%; p = 0,35). RESULTS: Recurrent laryngeal nerve injury and
      hypoparathyroidism are most common complications after thyroid surgery. Total
      thyroidectomy and reoperation are risk factors of recurrent laryngeal nerve
      injury and hypoparathyroidism.

PMID- 16903333
TI  - [The use of palisade technique in tympanoplasties after Heermann].
AB  - INTRODUCTION: The palisade tympanoplasties-technique with using of tragal and
      conchal autografts for reconstruction of the tympanic membrane and the auditory
      canal wall was described. MATERIAL AND METHODS: The operation started with the
      endaural incision. Tragal and conchal autograft palisade fragments with
      perichondrium for reconstruction of the tympanic membrane and the auditory canal
      wall have been used up to 1996 in 15,300 cases. We placed palisaded cartilage
      fragments parallel to the manubrium of the malleus in type I tympanoplasties and
      in type II or III procedures parallel to the long process of the incus. The
      "tunnel plasty" in the eustachian tubal entrance is performed with "simmering",
      "architrave" and "anti-architrave" to keep the tubal entrance open. This "tunnel
      plasty" results in a nice reconstruction of the tympano-meatal niche. The
      "annulus-stapes plate" in type III tympanoplasties replaces the function of the
      incus, crossing the promontory and reducing adhesions. This annulus-stapes bridge
      is fixed with a further palisade cartilage, "step plasty", which connects the
      "tunnel-plasty" with "annulus-stapes plate". The palisade-epitympanum-antrum
      plasty allows ventilation of the antrum via a tunnel constructed of well-fitting
      parallel pieces of cartilage fixed by self-tension (no glue) and replacing the
      bony canal wall. The "columella-tunnel plasty" has an L-shaped notch in the
      "annulus-stapes plate" fixing a columella of cartilage, placed in the oval
      window. Only in a case with a narrow oval window niche, a type IV palisade plasty
      can be performed or a prosthesis placed. RESULTS: The "annulus-stapes cartilage
      plate" is more stable reconstruction in type III tympanoplasties than are incus
      of foreign body interpositions. Adhesions on the promontory are found more often
      with fascia than with cartilage fragments. Histologic study of autograft
      cartilage showed good preservation of cartilage cells even 26 years after
      transplantation. CONCLUSIONS: The use of palisade cartilage technique brings very
      good functional and better long-term results.

PMID- 16903334
TI  - [Results of treatment with tympanostomy tubes in children with otitis media with
      effusion].
AB  - INTRODUCTION: Otitis media with effusion is a common problem in childhood. The
      tympanostomy tubes is a standard treatment of persistent otitis media with
      effusion in children which improves hearing level. However some pathological
      changes of the tympanic membrane and middle ear few years after treatment are
      observed. The aim of the study was prevalence of middle ear sequelaes in children
      with persistent otitis media with effusion treated by tympanostomy tubes 4-10
      years after treatment. MATERIAL AND METHODS: The group of 61 patients aged
      between 1-13 with otitis media with effusion treated by tympanostomy tubes in
      Department of Otolaryngology Childrenis Hospital in Warsaw between 1994-2001 were
      controlled. 113 ears treated with tympanostomy tubes were examined 4-10 years
      after treatment. At the examination otomicroscope, pure-tone audiometry and
      tympanometry were used. RESULTS: Out of the 113 ears after ventilation tubes
      insertion as a method of otitis media with effusion treatment in 83 (73%)
      developed one or more middle ear sequelaes. Myringosclerosis in 47 ears (41,59%),
      segmental atrophy in 19 ears (16,81%), atrophy in 14 ears (12,38%), disfunction
      of Eustachian tube in 8 ears (7,07%), otitis media with effusion in 7 ears
      (6,19%), perforation of tympanic membrane in 6 ears (5,3%), chronic otitis media
      in 2 ears (1,76%), retraction pocket in 2 ears (1,76%) and tympanostomy tube in
      the middle ear cavity in 1 ear (0,88%) were found. No cases of cholesteatoma were
      found. In 22 ears (19,46%) the conductive hearing loss was greater than 20 dB. In
      4 ears (3,5%) mixed hearing loss and in 3 ears (2,6%) receptable hearing loss was
      diagnosed. Tympanogram type A was in 86 ears (76,1%), tympanogram type B was in
      11 ears (9,7%) and tympanogram type C was in 12 ears (12,6%). CONCLUSIONS: In
      children with otitis media with effusion treated with tympanostomy tubes the
      amount of sequelaes increased with time. In children with otitis media with
      effusion who started treatment with tympanostomy tubes in age to 4 years old the
      amount of sequelaes is less. The follow-up is recommended up to 8 years after the
      treatment.

PMID- 16903335
TI  - [A simple-irrigating system for endoscopic sinus surgery].
AB  - INTRODUCTION: The most troublesome problem during endoscopic surgery is fouling
      of the endoscope lens (tip) with blood. Irrigating systems are available on the
      market but they are relatively very expensive. We present our own simple
      irrigating system, very effective and inexpensive. MATERIAL AND METHODS: The
      system consists of: polyethylene catheter No 6, sterile intravenous line with
      interposed stopcock, 500 ml saline solution, endoscope. The catheter is fixed to
      the endoscope with sterile sticks and connected to the bottle of saline solution
      with intravenous line. During the operation the irrigant solution flow is
      controlled with interposed stopcock. CONCLUSIONS: A simple irrigating system
      allows cleaning of blood from the endoscope obviating the need for frequent
      removal of the endoscope from the nose. This allows more rapid and safer
      endoscopic surgery. It is very simple and cheap.

PMID- 16903336
TI  - [Management and therapy in functional aphonia: analysis of 500 cases].
AB  - INTRODUCTION: The article reviews current opinions on etiopathogenesis and
      management of functional total loss of the ability to produce loud voice.
      Psychogenic aphonia refers to involuntary whispering despite a basically normal
      larynx. MATERIAL AND METHODS: [corrected] The longitudinal study was carried out
      on 500 patients treated for psychogenic aphonia during 32 years (1972-2004). Of
      the facilitating techniques, the following were useful for phoniatric therapy:
      relaxation and respiration, gargle, chewing, pushing, inhalation phonation,
      masking, phonetic exercises. RESULTS: During the first day of vocal exercises the
      voice return to 410 patients (82%). The others required carrying on vocal
      therapy. CONCLUSIONS: The basic importance of phoniatric therapy is recovering
      the voice during the first day of vocal exercises. Sometimes the aphonic patient
      profits most from symptomatic voice therapy concurrent with psychotherapy.

PMID- 16903337
TI  - [Rare case of primary sinonasal tuberculosis].
AB  - INTRODUCTION: Tuberculosis, considering entry of infection, most frequent
      concerns the lungs. Rarely we observed extrapulmonary cases of tuberculosis
      within the bones, joints, urogenital organs and lymph nodes as well as within the
      head and neck region--larynx, middle ear, pharynx, tonsils, tongue, parotid
      glands and central nervous system. Sinonasal tuberculosis, either primary or
      secondary to pulmonary infection, is very rare, but should be considered in the
      differential diagnosis of sinonasal granulomas. The diagnosis of the head and
      neck tuberculosis is based on the medical patientis examination as well as on the
      bacteriological and histological study of the biopsy specimen. AIM: The aim of
      the study was to show own, very rare case of primary sinonasal tuberculosis.
      MATERIAL AND METHODS: We described a case of primary sinonasal tuberculosis in an
      adult female. She was suspected of the neoplastic disease. The diagnosis was
      based on the histopathology. The treatment was successful and consisted with
      antituberculous drug therapy and surgery (Functional Endoscopic Sinus Surgery).
      The patient was followed up for 12 months and during this time we did not notice
      any symptoms of recurrence. CONCLUSIONS: Tuberculosis of the head and neck region
      should be take in to consideration during the differential diagnostic of the
      neoplastic diseases.

PMID- 16903338
TI  - [Atypical Stafne bone cavity of the mandible].
AB  - The paper presents the case of atypical Stafne bone cavity in 41 years old male.
      The defect was situated under the mandibular nerve and second molar. There were
      the part of submandibular gland, arterial vesel and fat tissue in the 2 x 2 cm
      cavity.

PMID- 16903339
TI  - [A rare case of laryngeal leiomyoma].
AB  - INTRODUCTION: To report a rare case of laryngeal leiomioma. Tumors of smooth
      muscle origin are rare in the upper aerodigestive tract, due to the paucity of
      smooth muscle in the area. A review of the literature confirm that this kind of
      neoplasm is extremely rare in the larynx and not so many cases were described in
      the literature so far. We described classification, treatment and clinical course
      of laryngeal leiomioma. MATERIAL AND METHODS: We encountered such a tumor in a 68
      year-old men who was admitted to our Hospital. Hoarseness since 2 years was a
      main symptom. RESULTS: The tumor was removed endoscopically and was located under
      left vocal cord. The patient recovered well but after 6 months was admitted again
      to our Hospital due to recurrence of ailments. Tracheotomy and enlarged
      chordectomy on the left side of larynx was performed under general anesthesia.
      The tumor was encapsulated and could be completely resected. No complications
      were observed in the postoperative course and patient was discharged from the
      hospital in 5th day after operation. There was no evidence of loco regional
      recurrence 4 years post surgery and laryngeal function was preserved. All
      histological pictures of the specimens from the first and second operation
      indicated tumor as a laryngeal leiomioma. CONCLUSION: Laryngeal leiomioma is a
      very infrequent neoplasm and to our knowledge, this is the 38th case of laryngeal
      smooth muscle tumor to be reported in the world literature.

PMID- 16903340
TI  - [Severe sepsis as a complication of descending necrotizing mediastinitis due to a
      peritonsillar abscess. A case study].
AB  - Descending necrotic mediastinitis is a serious illness which, among others,
      follows acute bacterial infections located in a cervical area. One of the most
      frequent causes of this illness, not connected with surgical interventions, is a
      peritonsillar and peridental abscess. The process originally placed in the
      peritonsillar area spreads along the cervical fascia engulfs mediastinum.
      Inflammatory process of the mediastinum considerably worsens the prognosis and
      obligates to decisive surgical (mediastinum drainage) and pharmacological
      (antibiotic therapy) treatments. The following works presents the course of the
      illness of a 55-year-old man who was diagnosed with severe sepsis in the course
      of the peritonsillar abscess. After surgical provision of the abscess (incision)
      the patient was qualified for the therapy with activated protein C (Xigris,
      Lilly). The patient condition initially improved, however, after 8 days a
      descending necrotic mediastinitis with ambilateral pleural abscess was diagnosed.
      The administration of the treatment within 48 days of hospitalization (antibiotic
      therapy, thoracotomy, flow drainage of the mediastinum, tracheotomy,
      respirotherapy) brought about the effect of complete recovery.

PMID- 16903341
TI  - [Binder's syndrome--symptoms and treatment].
AB  - INTRODUCTION: The flat dorsum and short septum of the nose, enlarged nasal angle,
      small naso-labial angle, maxillary micrognathism, and augmented upper lip, what
      makes the concave midface profile are the symptoms of Binder syndrome
      (maxillonasal displasia). The treatment consists of nasal and maxillary
      correction followed by orthodontic rehabilitation. MATERIAL AND METHODS: Five
      cases affected with Binder syndrome (age: 5-20 years old) were observed. Two
      patients were surgically treated in age 14 and 20-year-old. Nose correction was
      performed--elongation of skin nasal septum and bone graft to dorsum. Three
      patients need the orthodontic treatment of occlusal class III. There was no
      indication to corrective osteotomy of maxilla. RESULTS: Five year long-term
      result after surgical nose correction is excellent. CONCLUSIONS: The treatment
      schedule in Binder syndrome depends on the progress of the symptoms in the face
      occlusion. Surgical treatment can be limited only to reconstruction of the nasal
      dorsum and apex or additionally maxillary advancement. Grafting to the osteo
      chondral scafold of the nose can be carry out from 14-year-old, and osteotomy of
      the nose or maxilla should be planned after 18-year-old. Every patient affected
      with maxillonasal displasia requires consultation and orthodontic treatment.

PMID- 16903342
TI  - [Primary multiple tumours in patients treated in Otolaryngological Department of
      Voivodenship Hospital Number 4 in Bytom].
AB  - The authors presented a specification of seven cases of multiple primary tumors
      treated in the Otolaryngological Department of Voivodenship Hospital No. 4 in
      Bytom (in the years 1991-2004). One case above-mentioned was described more
      closely. The presented case shows criterions for recognizing the malignant
      multiple primary tumors. The case describes a case of 42 years old patient
      treated for 3 primary tumors, metachronic--larynx, oral cavity and pharynx during
      12 years. Two tumors have been radicaly removed in surgical treatment, the third
      one was cured by irradiation. The authors show more frequent appearance of
      malignant multiple primary tumors and their not clear etiology and emphasizing
      the significance of systematic follow up examinations after the treatment of
      primary tumors.

PMID- 16903343
TI  - [Aggressive osteoblastoma of the larynx: case report].
AB  - Osteoblastoma agressiva is not often bone tumor, only locally malignant. There
      are not articles, describing extra skeleton localization. Authors presented case
      of 45 year old patient, who was treated because of Aggressive Osteoblastoma
      localized in larynx. Patient has received operation and irradiation treatment.
      The tumor localization and patients age--more than 35 year are unusual.

PMID- 16903344
TI  - [Review of the basic methods of surgical treatment of lacrimal duct stenosis].
AB  - Nasolacrimal duct obstruction is a common condition in patients who visit
      otolaryngologists and ophtalmologists. The patients complain of epiphora and
      blurred vision. Reconstruction of lacrimal drainage provides great improvement in
      a patient's quality of life. On the base of the world literature and the own
      experience, several surgical techniques of the lacrimal system are presented and
      analyzed regarding indications and results: dacryocystorhinostomy (DCR),
      canaliculodacryocystorhinostomy (CanDCR), con-junctivodacryocystorhinostomy
      (ConDCR) and intubation. External DCR usually involves extensive removal of bone
      at the lacrimal fossa and hence risks disruption of the lacrimal pump mechanism.
      The development of endonasal microsurgery (endoscope, microscope) have awakened
      interest in an internal DCR in treatment nasolacrimal obstruction. Endonasal
      microscopic dacryocystorhinostomy become an important alternative to the
      classical external DCR. This method preserves intact the normal function of the
      lacrimal pump, yields cosmetic excellent results and allows at the same time
      management of the concomitant sino-nasal pathology.

PMID- 16903345
TI  - [History of endonasal microsurgery of lacrimal system].
AB  - The history and development of surgical treatment of lacrimal system from
      rhinological point of view was presented. The lacrimal drainage system has
      provoked great deal of investigation throughout history, because ophtalmologists
      couldn't attain persistent and permeable drainage between the lacrimal and the
      nose. The change came, when first Italian rhinologist Toti described external
      dacryocystorhinostomy (DCR), and later West performed endonasal DCR. The use of
      microscope and endoscope in rhinosurgery caused the significant progress also in
      lacrimal surgery. The development of endonasal microsurgery enabled to introduce
      other non invasive procedure, such as endoscopic laser dacryocystorhinostomy or
      transcanalicular dacryo-cystorhinostomy (endo-canalicular DCR). One of the newest
      method in the treatment of complete and partial obstruction of lacrimal drainage
      system is also baloon dacryocystoplasty.

PMID- 16903346
TI  - [Hearing evaluation in patients with vertigo].
AB  - INTRODUCTION: Vertigo is one of the most frequent and disturbing sensations that
      the practicing otolaryngologist is called upon to treat. Vertigo is the illusory
      sensation of motion. True vertigo is caused by pathology in the peripheral end
      organ, the vestibular nerve, and the pathways that connect them in the brainstem
      and rarely, in the cortex. AIM: The aim of this study was to evaluate hearing in
      people with vertigo according to the etiology of balance disorders. The study
      comprised 127 patients treated in our clinic between 1999 and 2004, 88 women and
      39 men (254 ears) aged 24-90 years. The average age was 56. METHODS: Hearing
      tests (pure tone audiometry, speech audiometry, impedance audiometry, auditory
      brainstem responses, OAE) as well as vestibular function tests
      (electronystagmography, rotational chair tests, caloric tests) were performed. In
      order to evaluate the nature of vertigo radiological diagnostics (head and
      cervical computer tomography, vascular diagnostics using Doppler sonography) was
      performed. RESULTS: Audiometric testing showed impaired hearing in 71 of 127
      subjects. Among 73 patients with vertigo of vascular origin caused by vertebrae
      basilar insufficiency, bilateral cochlear lesion was noticed in 33 cases and
      unilateral in 9. In 8 patients with cervical ankylosing spondylitis 3 had
      cochlear hearing loss (1--unilateral, 2--bilateral). CONCLUSIONS: In our group of
      patients with vertigo in the most of cases the hearing loss was on cochlear
      origin.

PMID- 16903347
TI  - [Distortion product otoacoustic emissions before and after one year exposure to
      impulse noise].
AB  - INTRODUCTION: Firearms are a common source of impulse noise that may be very
      harmful to the auditory organ. Impulse noise from weapons and explosions
      continually produces hearing damage among military personnel. The discovery of
      otoacoustic emission (OAE) has given a new possibility of early diagnosis of
      noise induced hearing loss. The transiently evoked otoacoustic emission (TEOAE)
      and distortion product otoacoustic emission (DPOAE) are non-invasive, objective
      and frequency specific audiometric tests for evaluating outer hair cell function.
      The aim of the study was to asses the effects of exposure to impulse noise on
      DPOAE after one year of the obligatory military service. MATERIAL AND METHODS:
      The study comprised 92 (184 ears) soldiers, subjected to impulse noise during
      military service. The examine group was divided according total noise exposure.
      The control group consisted of secondary school students not exposed to noise.
      DPOAE was recorded before and after one year of military service. RESULTS: After
      military service significant deterioration of DPOAE level was observed at
      frequencies of 1, 3, and 4 kHz on the right ear and 2, 5 and 6 kHz left one.
      CONCLUSIONS: 1. Reduction of DPOAE amplitude connected all frequencies. 2. We did
      not notice significant differences between groups connected total noise exposure.

PMID- 16903348
TI  - [Evaluation of the risk on hearing loss at soldiers].
AB  - INTRODUCTION: Noise produced by weapons may be harmful to soldiers during
      military service. Exposure to impulse noise during compulsory military service
      depends on the number of shots, explosion impulses, distance of injured ear from
      causal firearm as well as on the use of hearing protectors. Weapons produce
      impulse noises, which are characterized by peak pressure level and frequency. The
      purpose of this work was to calculate and estimate risk on hearing at soldiers
      during one year of the military service. MATERIAL AND METHODS: The study
      comparised three groups of soldiers with different kind of exposure to noise
      divided according total noise exposure. In order to evaluate the amount of the
      exposure to impulse noise the total level of noise and the spectrum analysis were
      performed for all types of weapons, which were used during military service. The
      equivalent continuous A-weighted sound pressure level, L A eq, Te [dB], maximum A
      weighted sound pressure level, L A max [dB] and C weighted peak sound pressure
      level, L C peak [dB] were measured. RESULTS: The highest total exposure to noise
      concerned group I (2222,9 kPa(2)/s for right ear and 22212,8 kPa(2)/s for left
      one) with total exposure time 248,3 minutes. In the II group estimated total
      exposure to noise was 611,8 kPa(2)/s for right ear and 743,6 kPa(2)/s for left
      one. In the III group least exposed to noise, estimated total exposure to noise
      was 103 kPa(2)/s for right ear and 109 kPa(2)/s for left one with total time
      exposure 17,8 minutes. CONCLUSIONS: Difference between groups is dependent on
      kind of military service. Estimated exposure to weapons noise may prevent
      soldiers before hearing loss. We did not notice differences between sites of
      ears.

PMID- 16903349
TI  - Bacterial endophytes and their interactions with hosts.
AB  - Recent molecular studies on endophytic bacterial diversity have revealed a large
      richness of species. Endophytes promote plant growth and yield, suppress
      pathogens, may help to remove contaminants, solubilize phosphate, or contribute
      assimilable nitrogen to plants. Some endophytes are seedborne, but others have
      mechanisms to colonize the plants that are being studied. Bacterial mutants
      unable to produce secreted proteins are impaired in the colonization process.
      Plant genes expressed in the presence of endophytes provide clues as to the
      effects of endophytes in plants. Molecular analysis showed that plant defense
      responses limit bacterial populations inside plants. Some human pathogens, such
      as Salmonella spp., have been found as endophytes, and these bacteria are not
      removed by disinfection procedures that eliminate superficially occurring
      bacteria. Delivery of endophytes to the environment or agricultural fields should
      be carefully evaluated to avoid introducing pathogens.

PMID- 16903350
TI  - Sm1, a proteinaceous elicitor secreted by the biocontrol fungus Trichoderma
      virens induces plant defense responses and systemic resistance.
AB  - The soilborne filamentous fungus Trichoderma virens is a biocontrol agent with a
      well-known ability to produce antibiotics, parasitize pathogenic fungi, and
      induce systemic resistance in plants. Even though a plant-mediated response has
      been confirmed as a component of bioprotection by Trichoderma spp., the molecular
      mechanisms involved remain largely unknown. Here, we report the identification,
      purification, and characterization of an elicitor secreted by T. virens, a small
      protein designated Sm1 (small protein 1). Sm1 lacks toxic activity against plants
      and microbes. Instead, native, purified Sm1 triggers production of reactive
      oxygen species in monocot and dicot seedlings, rice, and cotton, and induces the
      expression of defense-related genes both locally and systemically in cotton. Gene
      expression analysis revealed that SM1 is expressed throughout fungal development
      under different nutrient conditions and in the presence of a host plant. Using an
      axenic hydroponic system, we show that SM1 expression and secretion of the
      protein is significantly higher in the presence of the plant. Pretreatment of
      cotton cotyledons with Sm1 provided high levels of protection to the foliar
      pathogen Colletotrichum sp. These results indicate that Sm1 is involved in the
      induction of resistance by Trichoderma spp. through the activation of plant
      defense mechanisms.

PMID- 16903351
TI  - Synergistic interactions of the plant cell death pathways induced by Phytophthora
      infestans Nepl-like protein PiNPP1.1 and INF1 elicitin.
AB  - Cell death plays a ubiquitous role in plant-microbe interactions, given that it
      is associated with both susceptible and resistance interactions. A class of cell
      death-inducing proteins, termed Nepl-like proteins (NLPs), has been reported in
      bacteria, fungi, and oomycetes. These proteins induce nonspecific necrosis in a
      variety of dicotyledonous plants. Here, we describe three members of the NLP
      family from the oomycete Phytophthora infestans (PiNPP1.1, PiNPP1.2, and
      PiNPP1.3). Using agroinfection with a binary Potato virus X vector, we showed
      that PiNPP1.1 induces cell death in Nicotiana benthamiana and the host plant
      tomato. Expression analyses indicated that PiNPP1.1 is up-regulated during late
      stages of infection of tomato by P. infestans. We compared PiNPP1.1 necrosis
      inducing activity to INF1 elicitin, a well-studied protein that triggers the
      hypersensitive response in Nicotiana spp. Using virus-induced gene silencing, we
      showed that the cell death induced by PiNPP1.1 is dependent on the ubiquitin
      ligase-associated protein SGT1 and the heat-shock protein HSP90. In addition,
      cell death triggered by PiNPP1.1 but not that by INF1 was dependent on the
      defense-signaling proteins COI1, MEK2, NPR1, and TGA2.2, suggesting distinct
      signaling requirements. Combined expression of PiNPP1.1 and INF1 in N.
      benthamiana resulted in enhanced cell death, suggesting synergistic interplay
      between the two cell-death responses. Altogether, these results point to
      potentially distinct but interacting cell-death pathways induced by PiNPP1.1 and
      INF1 in plants.

PMID- 16903352
TI  - The Tobacco mosaic virus replicase protein disrupts the localization and function
      of interacting Aux/IAA proteins.
AB  - Previously, we identified a correlation between the interaction of the Tobacco
      mosaic virus (TMV) 126/183-kDa replicase with the auxin response regulator indole
      acetic acid (IAA)26/PAP1 and the development of disease symptoms. In this study,
      the TMV replicase protein is shown to colocalize with IAA26 in the cytoplasm and
      prevent its accumulation within the nucleus. Furthermore, two additional auxin
      (Aux)/IAA family members, IAA27 and IAA18, were found to interact with the TMV
      replicase and displayed alterations in their cellular localization or
      accumulation that corresponded with their ability to interact with the TMV
      replicase. In contrast, the localization and accumulation of noninteracting
      Aux/IAA proteins were unaffected by the presence of the viral replicase. To
      investigate the effects of the replicase interaction on Aux/IAA function,
      transgenic plants expressing a proteolysis-resistant IAA26-P108L-green
      fluorescent protein (GFP) protein were created. Transgenic plants accumulating
      IAA26-P108L-GFP displayed an abnormal developmental phenotype that included
      severe stunting and leaf epinasty. However, TMV infection blocked the nuclear
      localization of IAA26-P108L-GFP and attenuated the developmental phenotype
      displayed by the transgenic plants. Combined, these findings suggest that TMV
      induced disease symptoms can be attributed, in part, to the ability of the viral
      replicase protein to disrupt the localization and subsequent function of
      interacting Aux/IAA proteins.

PMID- 16903353
TI  - At-4/1, an interactor of the Tomato spotted wilt virus movement protein, belongs
      to a new family of plant proteins capable of directed intra- and intercellular
      trafficking.
AB  - The Tomato spotted wilt virus (TSWV) encoded NSm movement protein facilitates
      cell-to-cell spread of the viral genome through structurally modified
      plasmodesmata. NSm has been utilized as bait in yeast two-hybrid interaction trap
      screenings. As a result, a protein of unknown function, called At-4/1, was
      isolated from an Arabidopsis thaliana GAL4 activation domain-tagged cDNA library.
      Using polyclonal antibodies against bacterially expressed At-4/1, Western blot
      analysis of protein extracts isolated from different plant species as well as
      genome database screenings showed that homologues of At-4/1 seemed to be encoded
      by many vascular plants. For subcellular localization studies, At-4/1 was fused
      to green fluorescent protein, and corresponding expression vectors were used in
      particle bombardment and agroinfiltration assays. Confocal laser scannings
      revealed that At-4/1 assembled in punctate spots at the cell periphery. The
      protein accumulated intracellularly in a polarized fashion, appearing in only one
      half of a bombarded epidermal cell, and, moreover, moved from cell to cell,
      forming twin-structured bodies seemingly located at both orifices of the
      plasmodesmatal pore. In coexpression studies, At-4/1 colocalized with a plant
      virus movement protein TGBp3 known to reside in endoplasmic reticulum-derived
      membrane structures located in close vicinity to plasmodesmata. Thus, At-4/1
      belongs to a new family of plant proteins capable of directed intra- and
      intercellular trafficking.

PMID- 16903354
TI  - Mutations in the lrpE gene of Ralstonia solanacearum affects Hrp pili production
      and virulence.
AB  - The Ralstonia solanacearum hrpB-regulated gene lrpE (hpx5/brg24) encodes a PopC
      like leucine-rich repeat (LRR) protein that carries 11 tandem LRR in the central
      region. Defects in the lrpE gene slightly reduced the virulence of R.
      solanacearum on host plants and changed the bacterial morphology leading to the
      formation of large aggregates in a minimal medium. The aggregation in the
      deltalrpE background required the presence of a functional Hrp type III secretion
      system. In wild-type R. solanacearum, Hrp pili disappeared from the bacterial
      surface at the end of the exponential growth phase, when the pili form into long
      bundles. However, even in the late growth phase, bundled Hrp pili were still
      observed on the cell surface of the deltalrpE mutant. Such bundles were entangled
      and anchored the mutant cells in the aggregates. In contrast to PopC, LrpE
      accumulated in bacterial cells and did not translocate into plant cells as an
      effector protein. The expression levels of hrp genes increased three- to fivefold
      in the deltalrpE background compared with those in the wild type. We propose that
      LrpE may negatively regulate the production of Hrp pili on the cell surface of R.
      solanacearum to disperse bacterial cells from aggregates. In turn, dispersal may
      contribute to the movement of the pathogen in the plant vascular system and, as a
      consequence, the pathogenicity of R. solanacearum.

PMID- 16903355
TI  - Overexpression of BetS, a Sinorhizobium meliloti high-affinity betaine
      transporter, in bacteroids from Medicago sativa nodules sustains nitrogen
      fixation during early salt stress adaptation.
AB  - Sinorhizobium meliloti possesses several betaine transporters to cope with salt
      stress, and BetS represents a crucial high-affinity glycine and proline betaine
      uptake system involved in the rapid acquisition of betaines by cells subjected to
      osmotic upshock. Using a transcriptional lacZ (beta-galactosidase) fusion, we
      showed that betS is expressed during the establishment of the symbiosis and in
      mature nitrogen-fixing nodules. However, neither Nod nor Fix phenotypes were
      impaired in a betS mutant. BetS is functional in isolated bacteroids, and its
      activity is strongly activated by high osmolarity. In bacteroids from a betS
      mutant, glycine betaine and proline betaine uptake was reduced by 85 to 65%,
      indicating that BetS is a major component of the overall betaine uptake activity
      in bacteroids in response to osmotic stress. Upon betS overexpression (strain
      UNA349) in free-living cells, glycine betaine transport was 2.3-fold higher than
      in the wild-type strain. Interestingly, the accumulation of proline betaine, the
      endogenous betaine synthesized by alfalfa plants, was 41% higher in UNA349
      bacteroids from alfalfa plants subjected to 1 week of salinization (0.3 M NaCl)
      than in wild-type bacteroids. In parallel, a much better maintenance of nitrogen
      fixation activity was observed in 7-day-salinized plants nodulated with the
      overexpressing strain than in wild-type nodulated plants. Taken altogether, these
      results are consistent with the major role of BetS as an emergency system
      involved in the rapid uptake of betaines in isolated and in planta osmotically
      stressed bacteroids of S. meliloti.

PMID- 16903356
TI  - Characterization of the recombinant forms arising from a Potato virus X chimeric
      virus infection under RNA silencing pressure.
AB  - Recombination is a frequent phenomenon in RNA viruses whose net result is largely
      influenced by selective pressures. RNA silencing in plants acts as a defense
      mechanism against viruses and can be used to engineer virus resistance. Here, we
      have investigated the influence of RNA silencing as a selective pressure to favor
      recombinants of PVX-HCT, a chimeric Potato virus X (PVX) vector carrying the
      helper-component proteinase (HC-Pro) gene from Plum pox virus (PPV). All the
      plants from two lines expressing a silenced HC-Pro transgene were completely
      resistant to PPV. However a significant proportion became infected with PVX-HCT.
      Analysis of viral RNAs accumulating in silenced plants revealed that PVX-HCT
      escaped silencing-based resistance by removal of the HC-Pro sequences that
      represented preferential targets for transgene-promoted silencing. The virus
      vector also tended to lose the HC-Pro insert when infecting transgenic plants
      containing a nonsilenced HC-Pro transgene or wild-type (wt) Nicotiana benthamiana
      plants. Nevertheless, loss of HC-Pro sequences was faster in nonsilenced
      transgenic plants than in wt plants, suggesting the transgene plays a role in
      promoting a higher selective pressure in favor of recombinant virus versions.
      These results indicate that the outcome of recombination processes depends on the
      strength of selection pressures applied to the virus.

PMID- 16903357
TI  - Analysis of Nod-factor-induced calcium signaling in root hairs of symbiotically
      defective mutants of Lotus japonicus.
AB  - Nodulation (Nod)-factor signaling molecules are essential for rhizobia to
      initiate the nitrogen-fixing symbiotic interaction with legumes. Using a dual dye
      ratiometric calcium imaging technique, we have shown that 10 nM Nod factor added
      to roots of Lotus japonicus seedlings induces an intracellular calcium increase
      (calcium flux) that precedes oscillations in intracellular calcium (calcium
      spiking). The calcium flux was not observed with 1 or 0.1 nM Nod factor, which
      did induce calcium spiking. The calcium flux was variable in timing of initiation
      and duration and was observed in approximately half of the root hairs examined.
      Representatives from 11 complementation groups of symbiotically defective mutants
      were analyzed for the calcium flux. Mutants from four groups (sym6, ccamk, sym35,
      and nin) which retained calcium spiking all showed a normal calcium flux. Two
      classes of mutants (nfr1 and nfr5) lacked both calcium influx and calcium
      spiking, whereas five classes of mutants (symRK, castor, pollux, nup133, and
      sym24) defective for calcium spiking retained a calcium flux. There was no
      correlation between calcium spiking and induction of root hair deformation by Nod
      factor. We propose that increased bacterial numbers within infection foci in root
      hairs leads to accumulation of Nod factor to sufficient levels to activate the
      calcium flux, and this may drive infection thread growth.

PMID- 16903359
TI  - Antisense expression of the Arabidopsis thaliana AtPGIP1 gene reduces
      polygalacturonase-inhibiting protein accumulation and enhances susceptibility to
      Botrytis cinerea.
AB  - Polygalacturonases (PGs) hydrolyze the homogalacturonan of plant cell-wall pectin
      and are important virulence factors of several phytopathogenic fungi. In response
      to abiotic and biotic stress, plants accumulate PG-inhibiting proteins (PGIPs)
      that reduce the activity of fungal PGs. In Arabidopsis thaliana, PGIPs with
      comparable activity against BcPG1, an important pathogenicity factor of the
      necrotrophic fungus Botrytis cinerea, are encoded by two genes, AtPGIP1 and
      AtPGIP2. Both genes are induced by fungal infection through different signaling
      pathways. We show here that transgenic Arabidopsis plants expressing an antisense
      AtPGIP1 gene have reduced AtPGIP1 inhibitory activity and are more susceptible to
      B. cinerea infection. These results indicate that PGIP contributes to basal
      resistance to this pathogen and strongly support the vision that this protein
      plays a role in Arabidopsis innate immunity.

PMID- 16903358
TI  - GacS-dependent production of 2R, 3R-butanediol by Pseudomonas chlororaphis O6 is
      a major determinant for eliciting systemic resistance against Erwinia carotovora
      but not against Pseudomonas syringae pv. tabaci in tobacco.
AB  - Root colonization by a plant-beneficial rhizobacterium, Pseudomonas chlororaphis
      O6, induces disease resistance in tobacco against leaf pathogens Erwinia
      carotovora subsp. carotovora SCC1, causing soft-rot, and Pseudomonas syringae pv.
      tabaci, causing wildfire. In order to identify the bacterial determinants
      involved in induced systemic resistance against plant diseases, extracellular
      components produced by the bacterium were fractionated and purified. Factors in
      the culture filtrate inducing systemic resistance were retained in the aqueous
      fraction rather than being partitioned into ethyl acetate. Fractionation on high
      performance liquid chromatography followed by nuclear magnetic resonance mass
      spectrometry analysis identified the active compound as 2R, 3R-butanediol. 2R, 3R
      butanediol induced systemic resistance in tobacco to E. carotovora subsp.
      carotovora SCC1, but not to P. syringae pv. tabaci. Treatment of tobacco with the
      volatile 2R, 3R-butanediol enhanced aerial growth, a phenomenon also seen in
      plants colonized by P. chlororaphis O6. The isomeric form of the butanediol was
      important because 2S, 3S-butandiol did not affect the plant. The global sensor
      kinase, GacS, of P. chlororaphis O6 was a key regulator for induced systemic
      resistance against E. carotovora through regulation of 2R, 3R-butanediol
      production. This is the first report of the production of these assumed
      fermentation products by a pseudomonad and the role of the sensor kinase GacS in
      production of 2R, 3R-butanediol.

PMID- 16903360
TI  - A cost-function approach to rival penalized competitive learning (RPCL).
AB  - Rival penalized competitive learning (RPCL) has been shown to be a useful tool
      for clustering on a set of sample data in which the number of clusters is
      unknown. However, the RPCL algorithm was proposed heuristically and is still in
      lack of a mathematical theory to describe its convergence behavior. In order to
      solve the convergence problem, we investigate it via a cost-function approach. By
      theoretical analysis, we prove that a general form of RPCL, called distance
      sensitive RPCL (DSRPCL), is associated with the minimization of a cost function
      on the weight vectors of a competitive learning network. As a DSRPCL process
      decreases the cost to a local minimum, a number of weight vectors eventually fall
      into a hypersphere surrounding the sample data, while the other weight vectors
      diverge to infinity. Moreover, it is shown by the theoretical analysis and
      simulation experiments that if the cost reduces into the global minimum, a
      correct number of weight vectors is automatically selected and located around the
      centers of the actual clusters, respectively. Finally, we apply the DSRPCL
      algorithms to unsupervised color image segmentation and classification of the
      wine data.

PMID- 16903361
TI  - Dynamic coordination between robots: self-organized timing selection in a
      juggling-like ball-passing task.
AB  - This paper describes the hierarchical architecture for a rhythmic coordination
      between robots, which suits juggling-like tasks involving sensory-motor
      coordination. The authors' approach, which is interpreted as a "bidirectional
      weak coupling" to the environment, does not require either the environmental
      model or continuously monitoring the environment but can adapt the robots to a
      change in the environment, owing to the interaction between the robots and the
      environment at the ball contact. The proposed architecture contains two passive
      control mechanisms, the "open-loop stable mechanism" and the "entrainment
      mechanism," that lead to the emergence of self-organized temporal structure for
      rhythmic movement. This dynamic pattern in the whole system realizes the stable
      coordinated motion between robots. The authors demonstrate two motion patterns
      between two robots passing two balls, and confirm the effectiveness of the
      approach.

PMID- 16903362
TI  - An efficient dynamic system for real-time robot-path planning.
AB  - This paper presents a simple yet efficient dynamic-programming (DP) shortest path
      algorithm for real-time collision-free robot-path planning applicable to
      situations in which targets and barriers are permitted to move. The algorithm
      works in real time and requires no prior knowledge of target or barrier
      movements. In the case that the barriers are stationary, this paper proves that
      this algorithm always results in the robot catching the target, provided it moves
      at a greater speed than the target, and the dynamic-system update frequency is
      sufficiently large. Like most robot-path-planning approaches, the environment is
      represented by a topologically organized map. Each grid point on the map has only
      local connections to its neighboring grid points from which it receives
      information in real time. The information stored at each point is a current
      estimate of the distance to the nearest target and the neighbor from which this
      distance was determined. Updating the distance estimate at each grid point is
      done using only the information gathered from the point's neighbors, that is,
      each point can be considered an independent processor, and the order in which
      grid points are updated is not determined based on global knowledge of the
      current distances at each point or the previous history of each point. The robot
      path is determined in real time completely from the information at the robot's
      current grid-point location. The computational effort to update each point is
      minimal, allowing for rapid propagation of the distance information outward along
      the grid from the target locations. In the static situation, where both the
      targets and the barriers do not move, this algorithm is a DP solution to the
      shortest path problem, but is restricted by lack of global knowledge. In this
      case, this paper proves that the dynamic system converges in a small number of
      iterations to a state where the minimal distance to a target is recorded at each
      grid point and shows that this robot-path-planning algorithm can be made to
      always choose an optimal path. The effectiveness of this algorithm is
      demonstrated through a number of simulations.

PMID- 16903363
TI  - Deterministic approach to robust adaptive learning of fuzzy models.
AB  - This study is concerned with the adaptive learning of an interpretable Sugeno
      type fuzzy inference system, in a deterministic framework, in the presence of
      data uncertainties and modeling errors. The authors explore the use of Hinfinity
      estimation theory and least squares estimation for online learning of membership
      functions and consequent parameters without making any assumption and requiring a
      priori knowledge of upper bounds, statistics, and distribution of data
      uncertainties and modeling errors. The issues of data uncertainties, modeling
      errors, and time variations have been considered mathematically in a sensible
      way. The proposed robust approach to the adaptive learning of fuzzy models has
      been illustrated through the examples of adaptive system identification, time
      series prediction, and estimation of an uncertain process.

PMID- 16903364
TI  - A relative reward-strength algorithm for the hierarchical structure learning
      automata operating in the general nonstationary multiteacher environment.
AB  - A new learning algorithm for the hierarchical structure learning automata (HSLA)
      operating in the nonstationary multiteacher environment (NME) is proposed. The
      proposed algorithm is derived by extending the original relative reward-strength
      algorithm to be utilized in the HSLA operating in the general NME. It is shown
      that the proposed algorithm ensures convergence with probability 1 to the optimal
      path under a certain type of the NME. Several computer-simulation results, which
      have been carried out in order to compare the relative performance of the
      proposed algorithm in some NMEs against those of the two of the fastest
      algorithms today, confirm the effectiveness of the proposed algorithm.

PMID- 16903365
TI  - Rough-fuzzy collaborative clustering.
AB  - In this study, we introduce a novel clustering architecture, in which several
      subsets of patterns can be processed together with an objective of finding a
      common structure. The structure revealed at the global level is determined by
      exchanging prototypes of the subsets of data and by moving prototypes of the
      corresponding clusters toward each other. Thereby, the required communication
      links are established at the level of cluster prototypes and partition matrices,
      without hampering the security concerns. A detailed clustering algorithm is
      developed by integrating the advantages of both fuzzy sets and rough sets, and a
      measure of quantitative analysis of the experimental results is provided for
      synthetic and real-world data.

PMID- 16903366
TI  - Supervisory control of mobile sensor networks: math formulation, simulation, and
      implementation.
AB  - This paper uses a novel discrete-event controller (DEC) for the coordination of
      cooperating heterogeneous wireless sensor networks (WSNs) containing both
      unattended ground sensors (UGSs) and mobile sensor robots. The DEC sequences the
      most suitable tasks for each agent and assigns sensor resources according to the
      current perception of the environment. A matrix formulation makes this DEC
      particularly useful for WSN, where missions change and sensor agents may be added
      or may fail. WSN have peculiarities that complicate their supervisory control.
      Therefore, this paper introduces several new tools for DEC design and operation,
      including methods for generating the required supervisory matrices based on
      mission planning, methods for modifying the matrices in the event of failed
      nodes, or nodes entering the network, and a novel dynamic priority assignment
      weighting approach for selecting the most appropriate and useful sensors for a
      given mission task. The resulting DEC represents a complete dynamical description
      of the WSN system, which allows a fast programming of deployable WSN, a computer
      simulation analysis, and an efficient implementation. The DEC is actually
      implemented on an experimental wireless-sensor-network prototyping system. Both
      simulation and experimental results are presented to show the effectiveness and
      versatility of the developed control architecture.

PMID- 16903367
TI  - Parameter learning from stochastic teachers and stochastic compulsive liars.
AB  - This paper considers a general learning problem akin to the field of learning
      automata (LA) in which the learning mechanism attempts to learn from a stochastic
      teacher or a stochastic compulsive liar. More specifically, unlike the
      traditional LA model in which LA attempts to learn the optimal action offered by
      the Environment (also here called the "Oracle"), this paper considers the problem
      of the learning mechanism (robot, an LA, or in general, an algorithm) attempting
      to learn a "parameter" within a closed interval. The problem is modeled as
      follows: The learning mechanism is trying to locate an unknown point on a real
      interval by interacting with a stochastic Environment through a series of
      informed guesses. For each guess, the Environment essentially informs the
      mechanism, possibly erroneously (i.e., with probability p), which way it should
      move to reach the unknown point. When the probability of a correct response is p
      > 0.5, the Environment is said to be informative, and thus the case of learning
      from a stochastic teacher. When this probability p < 0.5, the Environment is
      deemed deceptive, and is called a stochastic compulsive liar. This paper
      describes a novel learning strategy by which the unknown parameter can be learned
      in both environments. These results are the first reported results, which are
      applicable to the latter scenario. The most significant contribution of this
      paper is that the proposed scheme is shown to operate equally well, even when the
      learning mechanism is unaware of whether the Environment ("Oracle") is
      informative or deceptive. The learning strategy proposed herein, called CPL-AdS,
      partitions the search interval into d subintervals, evaluates the location of the
      unknown point with respect to these subintervals using fast-converging E-optimal
      LRI LA, and prunes the search space in each iteration by eliminating at least one
      partition. The CPL-AdS algorithm is shown to provably converge to the unknown
      point with an arbitrary degree of accuracy with probability as close to unity as
      desired. Comprehensive experimental results confirm the fast and accurate
      convergence of the search for a wide range of values for the Environment's
      feedback accuracy parameter p, and thus has numerous potential applications.

PMID- 16903368
TI  - Rollover-free navigation for a mobile agent in an unstructured environment.
AB  - This paper introduces a navigation method for a teleoperated mobile agent (or
      robot) moving in an unstructured environment that includes unknown obstacles and
      uneven terrain, based on a guided-navigation algorithm (GNA) and a rollover
      prevention algorithm (RPA). Although the mobile agent is primarily driven by an
      operator at a remote site, it reacts autonomously for avoiding collision with
      obstacles and for preventing rollover when it suspects/detects possible collision
      or rollover. The autonomous reactive motion is normally unexpected, thus there
      exists the inconsistency between the intended motion and the controlled motion of
      the agent from the operator. A force-reflection technique utilizing a force
      feedback joystick is developed to manipulate this inconsistency. To verify the
      feasibility and effectiveness of the proposed navigation method, experiments with
      the Robot for Hazardous Application-Double Tracks (ROBHAZ-DT) (actual mobile
      agent) are successfully carried out.

PMID- 16903369
TI  - Variational learning for Gaussian mixture models.
AB  - This paper proposes a joint maximum likelihood and Bayesian methodology for
      estimating Gaussian mixture models. In Bayesian inference, the distributions of
      parameters are modeled, characterized by hyperparameters. In the case of Gaussian
      mixtures, the distributions of parameters are considered as Gaussian for the
      mean, Wishart for the covariance, and Dirichlet for the mixing probability. The
      learning task consists of estimating the hyperparameters characterizing these
      distributions. The integration in the parameter space is decoupled using an
      unsupervised variational methodology entitled variational expectation
      maximization (VEM). This paper introduces a hyperparameter initialization
      procedure for the training algorithm. In the first stage, distributions of
      parameters resulting from successive runs of the expectation-maximization
      algorithm are formed. Afterward, maximum-likelihood estimators are applied to
      find appropriate initial values for the hyperparameters. The proposed
      initialization provides faster convergence, more accurate hyperparameter
      estimates, and better generalization for the VEM training algorithm. The proposed
      methodology is applied in blind signal detection and in color image segmentation.

PMID- 16903370
TI  - Bidirectional PCA with assembled matrix distance metric for image recognition.
AB  - Principal component analysis (PCA) has been very successful in image recognition.
      Recent research on PCA-based methods has mainly concentrated on two issues,
      namely: 1) feature extraction and 2) classification. This paper proposes to deal
      with these two issues simultaneously by using bidirectional PCA (BD-PCA)
      supplemented with an assembled matrix distance (AMD) metric. For feature
      extraction, BD-PCA is proposed, which can be used for image feature extraction by
      reducing the dimensionality in both column and row directions. For
      classification, an AMD metric is presented to calculate the distance between two
      feature matrices and then the nearest neighbor and nearest feature line
      classifiers are used for image recognition. The results of the experiments show
      the efficiency of BD-PCA with AMD metric in image recognition.

PMID- 16903371
TI  - A novel incremental principal component analysis and its application for face
      recognition.
AB  - Principal component analysis (PCA) has been proven to be an efficient method in
      pattern recognition and image analysis. Recently, PCA has been extensively
      employed for face-recognition algorithms, such as eigenface and fisherface. The
      encouraging results have been reported and discussed in the literature. Many PCA
      based face-recognition systems have also been developed in the last decade.
      However, existing PCA-based face-recognition systems are hard to scale up because
      of the computational cost and memory-requirement burden. To overcome this
      limitation, an incremental approach is usually adopted. Incremental PCA (IPCA)
      methods have been studied for many years in the machine-learning community. The
      major limitation of existing IPCA methods is that there is no guarantee on the
      approximation error. In view of this limitation, this paper proposes a new IPCA
      method based on the idea of a singular value decomposition (SVD) updating
      algorithm, namely an SVD updating-based IPCA (SVDU-IPCA) algorithm. In the
      proposed SVDU-IPCA algorithm, we have mathematically proved that the
      approximation error is bounded. A complexity analysis on the proposed method is
      also presented. Another characteristic of the proposed SVDU-IPCA algorithm is
      that it can be easily extended to a kernel version. The proposed method has been
      evaluated using available public databases, namely FERET, AR, and Yale B, and
      applied to existing face-recognition algorithms. Experimental results show that
      the difference of the average recognition accuracy between the proposed
      incremental method and the batch-mode method is less than 1%. This implies that
      the proposed SVDU-IPCA method gives a close approximation to the batch-mode PCA
      method.

PMID- 16903372
TI  - Min-max hyperellipsoidal clustering for anomaly detection in network security.
AB  - A novel hyperellipsoidal clustering technique is presented for an intrusion
      detection system in network security. Hyperellipsoidal clusters toward maximum
      intracluster similarity and minimum intercluster similarity are generated from
      training data sets. The novelty of the technique lies in the fact that the
      parameters needed to construct higher order data models in general multivariate
      Gaussian functions are incrementally derived from the data sets using accretive
      processes. The technique is implemented in a feedforward neural network that uses
      a Gaussian radial basis function as the model generator. An evaluation based on
      the inclusiveness and exclusiveness of samples with respect to specific criteria
      is applied to accretively learn the output clusters of the neural network. One
      significant advantage of this is its ability to detect individual anomaly types
      that are hard to detect with other anomaly-detection schemes. Applying this
      technique, several feature subsets of the tcptrace network-connection records
      that give above 95% detection at false-positive rates below 5% were identified.

PMID- 16903373
TI  - Real-time face detection and lip feature extraction using field-programmable gate
      arrays.
AB  - This paper proposes a new technique for face detection and lip feature
      extraction. A real-time field-programmable gate array (FPGA) implementation of
      the two proposed techniques is also presented. Face detection is based on a naive
      Bayes classifier that classifies an edge-extracted representation of an image.
      Using edge representation significantly reduces the model's size to only 5184 B,
      which is 2417 times smaller than a comparable statistical modeling technique,
      while achieving an 86.6% correct detection rate under various lighting
      conditions. Lip feature extraction uses the contrast around the lip contour to
      extract the height and width of the mouth, metrics that are useful for speech
      filtering. The proposed FPGA system occupies only 15050 logic cells, or about six
      times less than a current comparable FPGA face detection system.

PMID- 16903374
TI  - Imbalanced learning with a biased minimax probability machine.
AB  - Imbalanced learning is a challenged task in machine learning. In this context,
      the data associated with one class are far fewer than those associated with the
      other class. Traditional machine learning methods seeking classification accuracy
      over a full range of instances are not suitable to deal with this problem, since
      they tend to classify all the data into a majority class, usually the less
      important class. In this correspondence, the authors describe a new approach
      named the biased minimax probability machine (BMPM) to deal with the problem of
      imbalanced learning. This BMPM model is demonstrated to provide an elegant and
      systematic way for imbalanced learning. More specifically, by controlling the
      accuracy of the majority class under all possible choices of class-conditional
      densities with a given mean and covariance matrix, this model can quantitatively
      and systematically incorporate a bias for the minority class. By establishing an
      explicit connection between the classification accuracy and the bias, this
      approach distinguishes itself from the many current imbalanced-learning methods;
      these methods often impose a certain bias on the minority data by adapting
      intermediate factors via the trial-and-error procedure. The authors detail the
      theoretical foundation, prove its solvability, propose an efficient optimization
      algorithm, and perform a series of experiments to evaluate the novel model. The
      comparison with other competitive methods demonstrates the effectiveness of this
      new model.

PMID- 16903375
TI  - Takagi-Sugeno fuzzy-model-based fault detection for networked control systems
      with Markov delays.
AB  - A Takagi-Sugeno (T-S) model is employed to represent a networked control system
      (NCS) with different network-induced delays. Comparing with existing NCS modeling
      methods, this approach does not require the knowledge of exact values of network
      induced delays. Instead, it addresses situations involving all possible network
      induced delays. Moreover, this approach also handles data-packet loss. As an
      application of the T-S-based modeling method, a parity-equation approach and a
      fuzzy-observer-based approach for fault detection of an NCS were developed. An
      example of a two-link inverted pendulum is used to illustrate the utility and
      viability of the proposed approaches.

PMID- 16903376
TI  - A control scheme for stable force-reflecting teleoperation over IP networks.
AB  - The problem of force-reflecting teleoperation over Internet protocol networks is
      addressed. The existence of time-varying communication delay and the possibility
      of data losses are taken into consideration. Since significant data loss may
      result in discontinuity of the reference trajectory transmitted through the
      communication channel, the proposed control scheme includes a filter that
      provides a smooth approximation of a possibly discontinuous reference trajectory.
      The stability of the overall system is guaranteed by a version of the input-to
      output stable small-gain theorem for functional differential equations. If the
      communication delay in the forward channel is an "approximately smooth" function
      of time, the proposed scheme guarantees that the slave manipulator tracks the
      delayed trajectory of the master within a prescribed small error.

PMID- 16903377
TI  - Robust fuzzy filter design for nonlinear systems with persistent bounded
      disturbances.
AB  - To date, nonlinear Linfinity-gain filtering problems have not been solved by
      conventional methods for nonlinear dynamic systems with persistent bounded
      disturbances. This study introduces a fuzzy filtering design to deal with the
      nonlinear Linfinity-gain filtering problem. First, the Takagi and Sugeno fuzzy
      model is employed to approximate the nonlinear dynamic system. Next, based on the
      fuzzy model, a fuzzy filter is developed to minimize the upper bound of Linfinity
      gain of the estimation error under some linear matrix inequality (LMI)
      constraints. Therefore, the nonlinear Linfinity-gain filtering problem is
      transformed into a suboptimal filtering problem, i.e., to minimize the upper
      bound of the Linfinity-gain of the estimation error subject to some LMI
      constraints. In this situation, the nonlinear Linfinity-gain filtering problem
      can be easily solved by an LMI-based optimization method. The proposed methods,
      which efficiently attenuate the peak of estimation error due to persistent
      bounded disturbances, extend the Linfinity-gain filtering problems from linear
      dynamic systems to nonlinear dynamic systems.

PMID- 16903378
TI  - BDPCA plus LDA: a novel fast feature extraction technique for face recognition.
AB  - Appearance-based methods, especially linear discriminant analysis (LDA), have
      been very successful in facial feature extraction, but the recognition
      performance of LDA is often degraded by the so-called "small sample size" (SSS)
      problem. One popular solution to the SSS problem is principal component analysis
      (PCA) + LDA (Fisherfaces), but the LDA in other low-dimensional subspaces may be
      more effective. In this correspondence, we proposed a novel fast feature
      extraction technique, bidirectional PCA (BDPCA) plus LDA (BDPCA + LDA), which
      performs an LDA in the BDPCA subspace. Two face databases, the ORL and the Facial
      Recognition Technology (FERET) databases, are used to evaluate BDPCA + LDA.
      Experimental results show that BDPCA + LDA needs less computational and memory
      requirements and has a higher recognition accuracy than PCA + LDA.

PMID- 16903379
TI  - Delay-dependent stability analysis and stabilization for discrete-time fuzzy
      systems with state delay: a fuzzy Lyapunov-Krasovskii functional approach.
AB  - This correspondence studies stability analysis and stabilization for discrete
      time Takagi and Sugeno fuzzy systems with state delay. First, a new fuzzy
      Lyapunov-Krasovskii functional (LKF) is constructed to derive a delay-dependent
      stability condition for open-loop fuzzy systems. Then, a delay-dependent
      stabilization approach based on a nonparallel distributed compensation scheme is
      provided for closed-loop fuzzy systems. Both state feedback and observer-based
      control cases are considered. The proposed stability and stabilization conditions
      are represented in terms of linear matrix inequalities (LMIs), which can be
      solved efficiently by using existing LMI optimization techniques. Finally, two
      numerical examples are given to illustrate the effectiveness of the proposed
      method.

PMID- 16903381
TI  - A registry for tissue engineering clinical trials.
AB  - Because tissue engineering products and processes are now being transferred from
      laboratory research into clinical applications, questions are being raised about
      what is the scope of an optimal clinical trial in this sector. A registry for
      these clinical trials is currently being established.

PMID- 16903380
TI  - Response to comments on "Hinfinity fuzzy control design for nonlinear singularly
      perturbed systems with pole placement constraints: an LMI approach".
AB  - This note responds to the comments published by Ni Zhao and Fu-Chun Sun in IEEE
      TRANSACTIONS ON SYSTEMS, MAN, AND CYBERNETICS-PART B, vol. 34, no. 6, p. 2422,
      Dec. 2004. Note that Theorems 3.1 and 3.2 are correct. The errors in the proofs
      have been fixed.

PMID- 16903382
TI  - Digital flow sensors: reaching new levels.
AB  - Microchips that combine sensor technology with digital signal processing on a
      single microchip can boost the performance and reduce the cost of measuring
      devices. How they can be employed in disposable applications such as liquid drug
      delivery and respiratory-flow monitoring is described here.

PMID- 16903383
TI  - The challenge to global acceptance of Part 3 of ISO 10993.
AB  - ISO 10993, Part 3: Testing for Genotoxicity, Carcinogenicity and Reproductive
      Effects, is not a globally recognised standard. The differences in these testing
      requirements in Europe, the United States and Japan are explained together with
      guidance on when to test and efficient strategies to adopt when marketing
      products in these regions.

PMID- 16903384
TI  - The sensing contact lens.
AB  - A novel contact lens with embedded sensors is being developed for continuous
      monitoring of the intraocular pressure in glaucoma patients. Its mode of
      operation and capabilities are described.

PMID- 16903385
TI  - The role of filtration in drug delivery systems.
AB  - In the race to provide the patient population with effective treatment systems,
      filtration technologies are playing a greater role in meeting the challenges.
      Good filter design is reviewed here.

PMID- 16903386
TI  - Effective use of virtual prototyping in device design.
AB  - Virtual testing as part of the product development process will reduce time and
      costs, but this method needs to be implemented correctly to gain these benefits.
      Five rules are described for effectively using analysis to drive design.

PMID- 16903387
TI  - Effectively incorporating risk management into quality systems.
AB  - Medical device manufacturers do not always recognise that the process of
      identifying and controlling risks is most effective if risk-related activities
      are incorporated into their quality systems. This article discusses a guidance
      document that provides practical suggestions for accomplishing this important
      task.

PMID- 16903388
TI  - Incorporating microfabrication in diagnostic instruments.
AB  - As new medical diagnostics are being developed, a new and more flexible approach
      to microfabrication is required to support the product development cycle. This
      article reviews some factors that have proved useful in the successful
      incorporation of microfabrication.

PMID- 16903389
TI  - Sequencing the human lifestyle.
AB  - Ever-expanding knowledge of human behaviour, which is being gathered as a side
      effect of the increasing use of wearable body monitors, is set to have a huge
      impact on health care.

PMID- 16903390
TI  - Roadmapping for medical devices.
AB  - Roadmapping can provide insight into emerging opportunities and competitive
      threats. The various processes to produce roadmaps are described and some
      examples are presented.

PMID- 16903391
TI  - Bringing together technology and market roadmaps.
AB  - Effective technology development is a difficult challenge. This article reports
      on one company's system, which has helped it achieve consistent, predictable
      success.

PMID- 16903392
TI  - Novel leak testing techniques.
AB  - Novel techniques are described that can be used whilst still applying the basic
      principles of leak measurement to test a range of medical devices.

PMID- 16903393
TI  - Filtration solutions.

PMID- 16903394
TI  - Make a mark.
AB  - Component identification and traceability are critical. This guide to component
      marking discusses the various technologies that can be employed.

PMID- 16903395
TI  - Dose counting in metered dose inhalers.

PMID- 16903396
TI  - Hospitals must overcome physician resistance before P4P can take root.

PMID- 16903397
TI  - Hospital execs scramble to face JCAHO policy changes.

PMID- 16903398
TI  - Technology & medicine. A guiding hand.

PMID- 16903399
TI  - Technology & medicine. Building a better limb.

PMID- 16903400
TI  - The good and the wired.

PMID- 16903401
TI  - Roles, service knowledge and priorities in the provision of palliative care: a
      postal survey of London GPs.
AB  - OBJECTIVES: To explore general practitioners' (GPs) current involvement in and
      attitudes towards the provision of palliative care in primary care. METHODS:
      Postal survey of 356 London-based GPs, assessing attitudes towards palliative
      care provision, district nursing and specialist palliative care services, and
      priorities for future service development. RESULTS: Currently, 65% of GPs were
      providing palliative care to patients on their list; 72% agreed or strongly
      agreed palliative care was a central part of their role; and 27% wanted to hand
      care over to specialists. Most GPs (66%) disagreed with the statement that
      'palliative care is mainly district nursing (DN) work'. Many were unaware of out
      of-hours DN and specialist palliative care services. Multi-variable analysis
      found four GP characteristics--larger practice size, more years experience as a
      GP, receipt of palliative care education, and current provision of palliative
      care--were associated with agreement that palliative care was central to a GP's
      role. CONCLUSION: A minority of NHS GPs in London would rather have no
      involvement in palliative care in primary care. Knowledge of current services for
      palliative care is generally poor among GPs. These findings highlight potential
      gaps in services, particularly in small practices. Specialists will need to
      consider these factors in working with GPs to develop primary palliative care and
      to enable greater access to specialist palliative care.

PMID- 16903402
TI  - Doctors' understanding of palliative care.
AB  - Palliative care has been challenged to share its message with a wider audience,
      and for many years it has been articulating an approach that is suitable for all
      patients. However, it is not clear how widely this message has been accepted. As
      part of a study into end-of-life care for heart failure, we conducted seven focus
      groups with doctors in general practice, palliative medicine, cardiology,
      geriatrics and general medicine. In these, we explored doctors' understanding of
      palliative care. Participants displayed a reasonable grasp of the wider concept
      of palliative care, but the specialists' role was ill-defined, reflected in
      scepticism about their place outside of cancer. Perceptions of palliative care
      fell into three broad areas: it was more than a service, about managing dying,
      and the concern of nurses, rather than doctors. Palliative care was welcomed as
      providing permission to fail, whilst representing a dilemma between quantity and
      quality of life for the interviewees. Our work suggests that specialist
      palliative care has been partially successful in getting their message across,
      and poor understanding or receptivity are not major barriers to implementing
      palliative care. Educational or other interventions to implement change in
      palliative care need to acknowledge the complex interaction of factors
      influencing physicians' behaviour.

PMID- 16903403
TI  - Hospital doctors' attitudes towards palliative care in Germany.
AB  - Experts from different areas strongly criticize the current level of palliative
      care in Germany, both inpatient and home care services. Apart from the experts'
      opinions, little is known in this context about the perspectives of hospital
      doctors working in different disciplines, such as surgery, internal medicine,
      gynaecology or anaesthesia. These doctors presumably treat many incurably ill
      patients with palliative care needs, but they usually have very little experience
      in palliative medicine. Their attitudes are particularly important because they
      are affected by the criticism and by future improvement strategies. To study
      their viewpoints, questionnaire surveys in five hospitals in the federal state of
      Brandenburg were performed, with 203 (69%) physicians participating. The results
      showed that the level of palliative care in hospitals was graded better than in
      the home care setting. Main needs for improvement were seen in the psychosocial
      support services and in the co-operation with outpatient services. In [corrected]
      the hospital physicians' view, palliative nursing care was of a higher standard
      than medical aspects [corrected] of care [corrected] The physicians showed great
      interest in improving their knowledge of [corrected] palliative care and in new
      specialist palliative care services. The conclusions were that three main
      strategies for improvement should be embarked on: (1) the establishment of
      integrated care systems to overcome financial and structural barriers between in-
      and outpatient care; (2) the establishment of further specialist palliative care
      services (eg, hospital-based palliative care teams); and (3) better education in
      palliative medicine.

PMID- 16903404
TI  - Does persistent involvement by the GP improve palliative care at home for end
      stage cancer patients?
AB  - OBJECTIVE: To analyse the effect of GP home visits on the granting of a terminal
      declaration (TD) and on place of death. PARTICIPANTS AND DESIGN: A total of 2025
      patients with cancer as the primary cause of death in the period 1997-1998, were
      investigated in a mortality follow-back design using the Danish Cancer Register
      and four administrative registers. The Danish TD can be issued by a physician for
      patients with an estimated prognosis of six months or less. The TD gives the
      right to economic benefits and increased care for the dying patient. SETTING: The
      island of Funen/Denmark. MAIN OUTCOME MEASURES: Main outcome--hospital death.
      Intermediate outcome--TD. RESULTS: A total of 38% of patients received a TD and
      56% died in hospital. GP home visits in the week before TD (odds ratio (OR):
      16.8; 95% CI: 8.2-34.4), as well as four weeks before TD (OR: 6.4; 95% CI: 4.5
      9.2) were associated with an increased likelihood of receiving a TD. GP home
      visits in the group with TD (OR: 0.18; 95% CI: 0.11-0.29) and the group without
      TD (OR: 0.08; 95% CI: 0.05-0.13) was inversely associated with hospital death. A
      dose-response relationship was found in both groups. CONCLUSION: Persistent
      involvement by the GP is associated with improved end-of-life care for cancer
      patients. Provided that temporal relations are taken into account, the mortality
      follow-back design can be a suitable and ethical research method to highlight and
      monitor end-of-life cancer care.

PMID- 16903405
TI  - Qualitative study of Chinese widows in Hong Kong: insights for psycho-social care
      in hospice settings.
AB  - In an exploratory, phenomenological study of seven Chinese widows in Hong Kong,
      five major themes are identified: relationship with the deceased, relationship
      with others, grief reactions, coping and emotional expression. This paper focuses
      on the first theme: the widows' relationship with the deceased husband along a
      timeline from the time of diagnosis to after death. The experiences in the final
      days with the deceased were frequently referred to when the informants talked
      about this theme. This paper aims to give added voice, based on the experience of
      Chinese widows, to the possible role of hospice and palliative care on
      influencing the bereavement experience. Issues of awareness and acceptance of
      death, the supportive environment and support for family carers, the moment of
      death, creation of legacies, and sensitivity towards cultural embedded practices,
      are discussed. It is hoped that the experiences of these bereaved widows will
      stimulate new research to elucidate and verify the findings reported in this
      paper.

PMID- 16903406
TI  - Grief support provided to caregivers of palliative care patients in Spain.
AB  - Grief support for relatives of patients in palliative care is recognized as a
      fundamental practice within palliative medicine. The aim of this research was to
      determine the nature and extent of grief support programs offered to relatives of
      patients in palliative care in Spain. A postal survey was carried out among
      members of the Spanish Society of Palliative Care. The members' names were
      obtained through the Society's 2000 Directory, which lists 160 different teams,
      of which 50% answered a questionnaire made up of 34 questions, some open-ended
      and others multiple choice. Results show that 88.6% of the services include grief
      support, that mainly emotional and one-to-one care is provided (92.4 and 89.9%,
      respectively), and that the number of psychologists and social workers in each
      team is limited. The risk factors most commonly taken into account by
      professionals are: absence of family support (36.92%) and the bereaved's case
      history (21.54%); while the most widely used diagnostic criteria for complicated
      bereavement are blame and depression (12.5 and 11.36%). In conclusion, it can be
      seen that bereavement services are not completely consolidated in Spain and there
      is a need for a greater variety of intervention strategies.

PMID- 16903407
TI  - The last two days of life of nursing home patients--a nationwide study on causes
      of death and burdensome symptoms in The Netherlands.
AB  - OBJECTIVES: The aim of this study was to identify the direct causes of death and
      to evaluate the presence of burdensome symptoms in the last two days of life of
      terminally ill nursing home (NH) patients. METHODS: Prospective study of patients
      with a maximum life-expectancy of six weeks in 16 nursing homes representative
      for The Netherlands (n = 463). Symptoms were measured after death in conscious
      patients with the Edmonton Symptom Assessment Scale (ESAS) and the Resident
      Assessment Instrument Minimum Data-Set Palliative Care (RAI MDS-PC draft 1.8).
      Direct causes of death were assessed in all patients. RESULTS: Most patients died
      from pneumonia, renal failure or dehydration. Loss of consciousness was common.
      The prevalence of burdensome symptom(s) at 48 and 24 hours before death was 51.3
      and 28.4%, respectively. CONCLUSION: In practice, it appears that, for many
      patients, the last days of life are spent unconscious or conscious with one or
      more burdensome symptom(s), which suggests the potential for improvement of
      symptom management.

PMID- 16903408
TI  - End-of-life care in community hospitals: the perceptions of bereaved family
      members.
AB  - OBJECTIVES: The perceptions of bereaved family members were obtained to evaluate
      the nature and quality of end-of-life care in community hospitals. DESIGN: During
      organizational case studies in six community hospitals in the South East and
      South West of England, bereaved family members were asked to participate in semi
      structured interviews. PARTICIPANTS: Fifty-one interviews were conducted with
      family members of patients who had received end-of-life care in a community
      hospital within the previous year. RESULTS: Respondents were very positive about
      the care they and the patient had received. They valued the convenience of access
      for frequent and long-stay visiting and the familiarity of the local hospital.
      Comparisons were made with more negative experiences at their nearest District
      General Hospital. Issues raised included the noise at the community hospitals,
      and the lack of contact with qualified nurses. DISCUSSION: The results of this
      study have implications for UK government initiatives, such as the National
      Framework for Older People, and the Department of Health's 'Keeping the NHS
      Local'.

PMID- 16903410
TI  - Impact of a postgraduate six-month rotation in palliative care on knowledge and
      attitudes of junior residents.
AB  - Fifty junior residents completed a six-month training period. An anonymous postal
      questionnaire was sent to collect the residents' opinions on improvements in
      their knowledge, perception of priorities and usefulness of training. Responses
      were rated from 5 (a great deal) to 1 (not at all improved). A total of 33 (66%)
      questionnaires were returned. A mean score of 4.48 was obtained on general
      improvement of knowledge, 4.91 +/- 0.29 on pain control, 4.17 +/- 0.58 on
      neurological symptoms, 4.09 +/- 0.77 on psychological symptoms, 4.64 +/- 0.60 on
      communication skills and 4.4 +/- 0.91 on physician attitudes. Some 58% of
      residents began the training with apprehension, 85% outlined their priorities and
      76% reached these objectives. A total of 70% were fully satisfied with the
      tuition and support received and 98% recommended such clinical rotation. Data
      suggest that a six-month rotation in palliative care results in high levels of
      perception of improvement in knowledge and satisfaction. Exposure to palliative
      care patients during clinical rotations in specialized centres must be
      encouraged.

PMID- 16903409
TI  - Carbamazepine-responsive paroxysmal nausea and vomiting in a patient with
      meningeal carcinomatosis.
AB  - In neurology, paroxysmal syndromes are well-known, eg, as manifestations of
      multiple sclerosis. We report a patient with meningeal carcinomatosis, who
      presented with therapy-refractory nausea and vomiting. The clinical suspicion of
      a paroxysmal syndrome prompted a trial of carbamazepine, which resulted in
      complete cessation of the symptoms. In cancer patients with central nervous
      system (CNS) involvement and therapy-refractory symptoms with sudden onset,
      carbamazepine treatment should be considered.

PMID- 16903411
TI  - Topical manuka honey for MRSA-contaminated skin ulcers.

PMID- 16903412
TI  - What is a stem cell niche?
AB  - Niche has become the most important issue in stem cell biology, but it is still a
      hypothetical notion that cannot be defined in a better way than the
      microenvironment surrounding stem cells. Using a melanocyte stem cell system as a
      model, we have analyzed the cellular and molecular requirements for
      differentiation of quiescent stem cells. Our results demonstrate the multiple
      subsets within the stem cell compartment and thus suggests the complexity of
      niche.

PMID- 16903413
TI  - New strategy for comprehensive analysis of gene functions in embryonic stem
      cells.
AB  - At present, the limitation of Phenotype-based genetic screening in embryonic stem
      cells (ESCs) is the diploid nature of the genome. Since it is known that cells
      deficient in the Bloom's syndrome gene (Blm) show an increased rate of homologous
      recombination, we have developed a new system to conditionally regulate the Blm
      allele for introduction of bi-allelic mutations across the genome. Transient
      deficiency of Blm induces homologous recombination not only between sister
      chromatids but also between homologous chromosomes, resulting in a high rate of
      loss of heterozygosity (LOH). Introduction of genome-wide mutations in ESCs can
      be achieved by retroviral vector. In combination, using genome-wide mutagenesis
      and transient loss of Blm expression, we have generated ES libraries with bi
      allelic mutations. These results show that this new system is very efficient for
      identifying gene functions in ESCs.

PMID- 16903414
TI  - Paternal dual barrier by Ifg2-H19 and Dlk1-Gtl2 to parthenogenesis in mice.
AB  - The functional difference between the maternal and paternal genome, which is
      characterized by epigenetic modifications during gametogenesis, that is genomic
      imprinting, prevents mammalian embryos from parthenogenesis. Genomic imprinting
      leads to nonequivalent expression of imprinted genes from the maternal and
      paternal alleles. However, our research showed that alteration of maternal
      imprinting by oocyte reconstruction using nongrowing oocytes together with
      deletion of the H19 gene, provides appropriate expression of maternally imprinted
      genes. Here we discuss that further alteration of paternally imprinted gene
      expressions at chromosomes 7 and 12 allows the ng/fg parthenogenetic embryos to
      develop to term, suggesting that the paternal contribution is obligatory for the
      descendant.

PMID- 16903415
TI  - Cell-cell fusion as a means to establish pluripotency.
AB  - Embryonic stem cells (ESCs), embryonic germ cells (EGCs), and embryonic carcinoma
      cells (ECCs) are three types of pluripotent cells derived from mammalian embryos.
      The three cell types are capable not only of self-renewal, but also of having the
      potential to give rise to cells of all tissue types in the fetal and adult body.
      In several reports, ESCs, ECCs, and EGCs have been described to reprogram somatic
      cells in vitro. After reprogramming caused by fusion, somatic cells exhibit
      various features of pluripotent cells: expression of pluripotency markers (e.g.,
      Oct4, nanog, and Rex-1), absence of tissue-specific gene expression, reactivation
      of inactive X chromosome of female somatic cells, demethylation, as well as
      histone modification. An activity in pluripotent stem cells appears to be capable
      of inducing the global changes inherent in the reprogramming of somatic cells.
      Investigations involving pluripotent stem cells will yield substantial insight
      into various fundamental biological processes, such as cellular differentiation
      and de-differentiation. Most importantly for the public, however, is that such
      studies might lead into cell-based therapies and as such have the potential to
      change regenerative medicine.

PMID- 16903416
TI  - Toward reprogramming cells to pluripotency.
AB  - The possibility of turning one somatic cell type into another may in the long run
      have beneficial applications in regenerative medicine. Somatic cell nuclear
      transfer (therapeutic cloning) may offer this possibility; however, ethical
      guidelines prevent application of this technology in many in countries. As a
      result, alternative approaches are being developed for altering cell fate. This
      communication discusses recent non-nuclear transfer-based in vitro approaches for
      reprogramming cells and enhancing their potential for differentiation toward
      various lineages.

PMID- 16903417
TI  - Molecular switches and developmental potential of adult stem cells.
AB  - Stem cell commitment and differentiation entails the successive loss of self
      renewal and developmental potential, and results in the final restriction to a
      terminally differentiated mature cell type. Hematopoiesis, the development of
      blood cells from hematopoietic stem cells in bone marrow, is particularly well
      studied, and at different branching points within the hematopoietic system
      multiple developmental intermediates have been identified. Here we describe a
      Flt3+ CD11b+ multipotent progenitor that can be amplified in vitro by a specific
      cytokine combination to high cell numbers, and following adoptive transfer into
      syngeneic mice, it generates dendritic cells but also additional mature cell
      types. By employing gene expression profiling with DNA microarrays and knockout
      mouse models, we demonstrate that the helix-loop-helix (HLH) transcription factor
      Id2 (inhibitor of DNA binding/differentiation 2) acts as a molecular switch in
      development of Langerhans cells (LCs), the cutaneous contingent of dendritic
      cells (DCs), and of specific DC subsets and B cells.

PMID- 16903418
TI  - Adult small intestinal stem cells: identification, location, characteristics, and
      clinical applications.
AB  - There are few systems which enable adult tissue stem cells to be studied.
      However, the gastrointestinal tract with its high degree of polarity, well
      defined cell migratory pathways, and dynamic cell replacement is a model tissue
      providing unique opportunities for stem cell study. Lineage tracking indicates
      that all cell replacement originates at well-defined stem cell positions, with an
      associated slower cell cycle. Radiobiological studies suggest a hierarchical stem
      cell compartment (actual and potential stem cells). Actual stem cells have an
      intolerance of genotoxic damage and die via apoptosis. Stem cells also
      selectively sort the old and new DNA strands at division, retaining the
      replication error free strands in the stem cell daughter. High genotoxic
      sensitivity and selective sorting of old and new DNA strands, provides extremely
      effective protective mechanisms against both replication and random errors. This
      provides a new explanation for the low cancer risk in the small intestine.

PMID- 16903419
TI  - Tracking stem cells in vivo.
AB  - Stem cells have been targeted to many organ systems specifically to replace
      scarred organs and to rejuvenate diseased organs. Even though our understanding
      of the versatility of stem cells is slowly unraveling, tracking these cells as
      they enter the body has become a very important field of study. In this chapter,
      we review various modalities for imaging stem cells and assess the advantages and
      shortcomings of each technique.

PMID- 16903420
TI  - Establishment of nuclear transfer embryonic stem cell lines from adult somatic
      cells by nuclear transfer and its application.
AB  - Nuclear transfer can be used to generate embryonic stem cell (ntESC) lines from a
      patient's own somatic cells. We have shown that ntESCs can be generated
      relatively easily from a variety of mouse genotypes and cell types of both sexes,
      even though it may be more difficult to generate clones directly. Several reports
      have already demonstrated that ntESCs can be used in regenerative medicine in
      order to rescue immunodeficient or infertile phenotypes. However, it is unclear
      whether ntES cells are identical to fertilized embryonic stem cells (ESCs). This
      review seeks to describe the phenotype and possible abnormalities of ntESC lines.

PMID- 16903421
TI  - Derivation of germ cells from embryonic stem cells.
AB  - Embryonic stem cells (ESCs), derivatives of cells of early mammalian embryos,
      have proven to be one of the most powerful tools in developmental and stem cell
      biology. When injected into embryos, ESCs can contribute to tissues derived from
      all three germ layers and to the germline. Prior studies have successfully shown
      that ESCs can recapitulate features of embryonic development by spontaneously
      forming somatic lineages in culture. Amazingly, recently it has been shown that
      mouse ESCs can also give rise to primordial germ cells (PGCs) in culture that are
      capable of undergoing meiosis and forming both male and female gametes. While the
      full potential of these ES-derived germ cells and gametes remains to be
      demonstrated, these discoveries provide a new approach for studying reproductive
      biology and medicine.

PMID- 16903422
TI  - Germline recruitment in mice: a genetic program for epigenetic reprogramming.
AB  - Germ cells provide an enduring link between generations and therefore must
      possess the fundamental ability of reprogramming their genome to generate a
      totipotent state. We wish to understand the molecular basis of the unique
      properties of the mammalian germ line. Recently we identified Blimp1, a potent
      transcriptional repressor of a histone methyltransferase subfamily, as a critical
      determinant of the germ cell lineage in mice. Surprisingly, Blimp1 expression
      marks the origin of the germ line in proximal epiblast cells in pregastrulation
      embryos, substantially earlier than previously thought. Furthermore, we showed
      that established primordial germ cells undergo extensive erasure of genome-wide
      histone H3 lysine 9 dimethylation (H3K9me2) and DNA methylation, two major
      repressive epigenetic modifications, and instead acquire high levels of H3-K27
      trimethylation (H3K27me3) in their migration period. We suggest that germline
      specification is a genetic system for the orderly reprogramming of the cells'
      epigenome toward a totipotent state, with reacquisition of totipotency-associated
      transcription factors and continued Blimp1 expression preventing their reversion
      to an explicit pluripotent state or somatic differentiation.

PMID- 16903423
TI  - Transplantation of germ line stem cells for the study and manipulation of
      spermatogenesis.
AB  - Transplantation of male germ line stem cells from a fertile donor to the testis
      of an infertile recipient restores donor-derived spermatogenesis in the recipient
      testis and the resulting sperm pass the donor genotype to the offspring of the
      recipient. Germ cell transplantation has been an invaluable tool to elucidate the
      biology of male germ line stem cells and their niche in the testis, develop
      systems to isolate and culture spermatogonial stem cells, examine defects in
      spermatogenesis, correct male infertility and introduce genetic changes into the
      male germ line. Although most widely studied in rodents, germ cell
      transplantation has been applied to larger mammals, including primates. Recently,
      ectopic grafting of testis tissue from diverse donor species, including primates,
      into a mouse host has opened an additional possibility to study spermatogenesis
      and to produce fertile sperm from immature donors. Testis xenografts are ideally
      suitable to study toxicants or drugs with the potential to enhance or suppress
      male fertility without the necessity of performing experiments in the target
      species. Therefore, transplantation of germ cells or xenografting of testis
      tissue represent powerful approaches for the study, preservation, and
      manipulation of male fertility.

PMID- 16903424
TI  - Progenitor cell-based myelination as a model for cell-based therapy of the
      central nervous system.
AB  - Diseases of the brain and spinal cord are especially daunting challenges for cell
      based strategies of repair, given the multiplicity of cell types within the adult
      central nervous system, and the precision with which they must interact in both
      space and time. Nonetheless, a number of diseases are especially appropriate for
      cell-based therapy, in particular those in which single phenotypes are lost.
      Foremost among these are the disorders of myelin, in which oligodendrocytes are
      the specific and often sole victims of the underlying disease process. These
      include not only the vascular, traumatic, and inflammatory demyelinations of
      adulthood, but also the congenital and childhood dysmyelinating syndromes of the
      pediatric leukodystrophies. These congenital disorders of myelin formation and
      maintenance may present especially compelling targets for cell-based neurological
      therapy.

PMID- 16903425
TI  - Adult neural stem cells and central nervous system repair.
AB  - It has long been believed that the adult mammalian central nervous system does
      not regenerate after injury. However, recent advances in the field of stem cell
      biology, including the identification of Musashi-1-positive neural stem cells
      (NSCs) or NSC-like cells, has provided new insight for the development of novel
      therapeutic strategies aimed at inducing regeneration in the damaged central
      nervous system (CNS). The major strategies for inducing regeneration in the
      damaged CNS can be classified into two subgroups: (1) activation of endogenous
      neural stem cells and (2) cell transplantation therapies. In this paper, we would
      like to summarize our recent findings on the functions of the neural RNA-binding
      protein Musashi-l expressed in neural stem cells in relation to insult-induced
      neurogenesis, and therapeutic interventions for spinal cord injury, especially
      focusing on the treatment of spinal cord injury in the acute phase with anti-IL-6
      receptor blocking antibody.

PMID- 16903426
TI  - Stem cell therapy for Parkinson's disease.
AB  - Transplantation of fetal dopaminergic (DA) neurons can produce symptomatic relief
      for patients with Parkinson's disease, but the technical and ethical difficulties
      have limited the application of this therapy. Neural precursor cells and
      embryonic stem cells (ESCs) are expected to be candidates of potential donor
      cells for transplantation. Human neural precursor cells obtained from the
      midbrain give rise to TH-positive neurons. The growth of the cells, however, is
      slow and the differentiation rate of DA neurons is still low for clinical
      application. Monkey ESCs give rise to midbrain DA neurons, and the transplanted
      ESC-derived neurospheres function as DA neurons, attenuating the neurological
      symptoms of the monkey Parkinson's disease model. These results suggest the
      possibility of using stem cells for the treatment of Parkinson's disease, but
      problems such as the low survival rate in vivo and tumor formation must be
      solved.

PMID- 16903427
TI  - President's message. Address to the Texas Dental Association House of Delegates,
      May 14, 2006.

PMID- 16903428
TI  - ADA Trustee's message. Address to the Texas Dental Association House of
      Delegates, May 11, 2006.

PMID- 16903429
TI  - The future of dentistry: challenges and opportunities, part 1.

PMID- 16903430
TI  - Oral B company distributed a line of toothbrushes of which they were so proud.

PMID- 16903431
TI  - Address to the Texas sections of the American & International College of
      Dentists.

PMID- 16903432
TI  - Ankylosis of traumatized permanent incisors: pathogenesis and current approaches
      to diagnosis and management.

PMID- 16903434
TI  - Accuracy of dental articulators.

PMID- 16903433
TI  - The 2005 C.T. Rowland Award orthodontic case report.
AB  - The C.T. Rowland award is presented annually by the Texas Orthodontic Study Club
      (formerly "Texas Tweed"). The award was first presented in 1954 in recognition of
      the group's president, C. T. Rowland. Applicants to the study club, which numbers
      almost 200 orthodontists from Texas and surrounding states, are required to
      present five cases for membership. These cases, with before and after records,
      represent a variety of malocclusions demonstrating the applicants' knowledge and
      expertise in diagnosing, treating, and finishing cases with quality results. The
      qualifying committee reviews each applicant's cases and, based on the difficulty
      of the original malocclusions and the degree of excellence of the finished
      result, chooses one person to receive their award. The 2005 winner of the C. T.
      Rowland award is Dr. Kyle Shannon. He is in the exclusive practice of
      orthodontics in Tulsa, OK.

PMID- 16903435
TI  - Medical gas and medical vacuum system maintenance.

PMID- 16903436
TI  - Oral and maxillofacial pathology case of the month. Oral candidiasis associated
      with inhaled corticosteroid use.

PMID- 16903437
TI  - Ethics in publishing: ghostwriting, conflicts of interest, and the impact factor.

PMID- 16903438
TI  - Oral health behaviors of children in low and high socioeconomic status families.
AB  - PURPOSE: This prospective longitudinal study compared the patterns of oral health
      behaviors between low and high socioeconomic status (SES) families participating
      in the Iowa Fluoride Study for a period of 9 years. METHODS: Information on oral
      health behaviors, including consumption of juices/juice drinks, soda pop, and
      powder-based drinks, dental visits, and tooth-brushing frequency, was collected
      longitudinally at periodic intervals from 6 to 108 months of age. Dental exams
      were conducted at 5 and 9 years of age. Classification of low socioeconomic
      status (SES; n=70) and high-SES (n= 128) children was based on baseline family
      income and mothers' education levels, with middle SES excluded. RESULTS: Low SES
      children consistently had significantly greater consumption of soda pop and
      powder-based beverages. There were, however, virtually no differences at any time
      point between groups in: (1) tooth-brushing frequency; (2) use of dentifrice; or
      (3) fluoride concentration in drinking water. Furthermore, the mean number of
      decayed and filled surfaces was significantly higher in the low-SES group.
      CONCLUSIONS: Results suggest that beverage consumption patterns are a key
      difference between high- and low-socioeconomic status families and could in part
      explain differences in caries experience between subjects of different SES.
      Modification of the pattern of soda pop and powder-based beverage consumption in
      the low-SES groups might reduce their caries experience.

PMID- 16903440
TI  - Survey of Iowa general dentists regarding the age 1 dental visit.
AB  - PURPOSE: The purpose of this study was to assess Iowa general dentists regarding
      the age 1 dental visit. METHODS: A 15-item survey was mailed to 1,521 licensed
      dentists to address their knowledge, attitudes, and behavior regarding the age 1
      dental visit. Chi-square statistics and logistic regression models were used to
      analyze data. RESULTS: Seven hundred fifteen (47%) useable surveys were returned
      from 2 mailings. Five hundred forty (76%) general dentists were familiar with the
      American Academy of Pediatric Dentistry (AAPD) age 1 dental visit recommendation.
      Most reported obtaining this information through continuing education (37%).
      Eleven percent believed the first dental visit should occur between 0 and 11
      months of age, and 66% reported seeing children younger than 2. "Prefer to refer
      infants to a pediatric dentist" (20%) was the most common reason for not seeing
      children 0 to 23 months old. Bivariate and multivariate logistic regression
      analyses indicated that dentists who believed children should have their first
      dental visit at 0 to 23 months and those willing to see children at age 0 to 23
      months were younger, more recent graduates, more likely to be female, aware of
      the AAPD recommendations, and were already seeing children 0 to 23 months.
      CONCLUSIONS: The majority of Iowa general dentists are aware of the AAPD age 1
      dental visit recommendation.

PMID- 16903439
TI  - Dental check-up of California's State Children's Health Insurance program.
AB  - PURPOSE: The purpose of this study was to compare dental utilization rates and
      related factors for children in California's State Children's Health Insurance
      dental program (SCHIP) to those for children with other types of dental insurance
      coverage or no coverage. METHODS: Data from the cross-sectional 2001 California
      Health Interview Survey for 10,454 children 2 to 11 years old were used. Data
      analyzed included: (1) the child's most recent dental visit; (2) dental insurance
      status; and (3) type of health insurance coverage. RESULTS: In 2001, 5% (+/
      SE=0.3) of California children had SCHIP dental coverage, 19% had Medicaid dental
      insurance (Denti-CAL), and 52% had private dental insurance. Twenty-three percent
      (+/-0.5) of children, however, had no dental insurance. Dental utilization rates
      varied significantly according to type of dental insurance. Compared to uninsured
      children, SCHIP children were more likely to use dental services within the past
      year (58% vs 72%). Annual dental utilization rates were even higher for Denti-CAL
      and privately insured children (76% and 80%, respectively). Factors associated
      with disparities in dental utilization included lack of a usual source of health
      care and lack of continuous health insurance. CONCLUSIONS: Significant
      disparities occurred by dental insurance status and type. Annual dental
      utilization rates for SCHIP children lagged behind those of children with Denti
      CAL or private dental insurance.

PMID- 16903441
TI  - Antibiotic prophylaxis for children with sickle cell disease: a survey of
      pediatric dentistry residency program directors and pediatric hematologists.
AB  - PURPOSES: The purposes of this study were to: (1) investigate the current
      clinical practice regarding the use of antibiotic prophylaxis by pediatric
      dentistry residency program directors and pediatric hematologists for children
      with sickle cell disease (SCD) requiring dental treatment; and (2) evaluate the
      perceived relative risk of bacteremia following specific dental procedures, as
      defined by pediatric dentistry residency program directors and pediatric
      hematologists. METHODS: A written survey depicting various clinical scenarios of
      SCD children requiring common dental procedures was mailed to directors of
      pediatric dental advanced education programs and distributed to pediatric
      hematologists attending the 2003 Annual Sickle Cell Disease Association of
      America conference in Washington, DC. RESULTS: Surveys were returned by 60%
      (N=34/57) of the pediatric dentistry residency program directors. The surveys
      were obtained from 51% of pediatric hematologists at the meeting (N=72/140). At
      least 50% of all respondents recommended prophylaxis for the following clinical
      situations: dental extractions, treatment under general anesthesia, and status
      post splenectomy. The perceived risk of infectious complication was highest for
      extractions, followed by restorative treatment and tooth polishing. Dental
      residency program directors were more likely (71%, N=24/34) to recommend
      additional antibiotic therapy for patients taking penicillin prophylaxis if they
      required an invasive oral surgical procedure. Conversely, only 38% (N=25/66) of
      pediatric hematologists recommended additional antibiotic therapy (P=.001).
      Eighty-six percent of dental residency program directors (N=25/29) chose
      amoxicillin for prophylaxis whereas only 62% of pediatric hematologists (N=36/58)
      recommended amoxicillin. (P<.05). CONCLUSIONS: There is a lack of consensus on
      the appropriate use of antibiotic prophylaxis in SCD children undergoing dental
      treatments. Further research and risk/benefit assessment is needed to create a
      unified approach.

PMID- 16903442
TI  - Management of a fused central incisor in association with a macrodont lateral
      incisor: a case report.
AB  - Fusion is developmental anomaly of the dental hard tissue and is defined as the
      joining of 2 developing tooth germs resulting in a single large tooth structure.
      Different treatment methods can be used according to the requirements of the
      situation. The purpose of this case report was to present the multidisciplinary
      treatment of a patient who had a permanent maxillary left central tooth fused
      with a supernumerary incisor and a macrodont permanent maxillary right lateral
      incisor. In the radiographic evaluation, it was determined that the fused tooth
      had 2 separate roots. The supernumerary tooth was extracted after hemisection,
      and endodontic treatment was performed on the remaining portion. The distal side
      of the macrodont lateral incisor was recontoured, and the right central incisor
      was reshaped with a strip crown to provide aesthetic appearance and to gain space
      for the alignment of teeth. Following the restoration of the incisors,
      orthodontic treatment was provided.

PMID- 16903443
TI  - A preventive approach to oral self-mutilation in Lesch-Nyhan syndrome: a case
      report.
AB  - Lesch-Nyhan syndrome is a rare X-linked recessive disorder of purine metabolism,
      caused by complete absence of the enzyme hypoxanthine-guanine phosphoribosyl
      transferase. Persons affected with this incurable disease are developmentally and
      physically delayed, and suffer from self-injurious behavior. The most typical
      feature results in partial or total destruction of perioral tissues. The purpose
      of this paper was to discuss a case of Lesch-Nyhan syndrome with self-mutilative
      behavior and lip injuries, including some suggestions of a preventive approach
      avoiding the extraction of teeth. A soft mouthguard fabricated to prevent the
      destruction of perioral soft tissues and combined psychiatric pharmacologic
      therapy proved to have satisfactory results.

PMID- 16903444
TI  - Trichodental dysplasia: a rare syndrome with distinct dental findings.
AB  - The association of fine, dry, short hair and the developmental absence of several
      teeth has been associated with a rare autosomal dominant variant of ectodermal
      dysplasia known as trichodental syndrome or trichodental dysplasia. The purpose
      of this study was to present the case of a 4-year-old boy with trichodental
      syndrome. Clinical, radiographic, and genetic manifestations are described, along
      with a pertinent review of the literature.

PMID- 16903445
TI  - Assessment of the effects of 2 sedation regimens on cardiopulmonary parameters in
      pediatric dental patients: a retrospective study.
AB  - PURPOSE: The purpose of this study was to evaluate the cardiopulmonary effects of
      2 sedation regimens during treatment: (1) oral meperidine and hydroxyzine with
      nitrous oxide (N2O); and (2) oral diazepam and hydroxyzine, submucosal
      meperidine, and N2O. Nitrous oxide was tapered to oxygen (O2) only 10 minutes
      following submucosal meperidine administration. METHODS: Sixty-two children were
      evaluated who met the following criteria: (1) history of uncooperative behavior;
      (2) ASA I or II; (3) nothing to eat or drink after midnight the night before the
      appointment; (4) an initial/recall exam prior to the sedation appointment; and
      (4) patients who met the American Academy of Pediatric Dentistry guidelines for
      sedation. Regimens I and II included 32 and 30 patients, respectively. A single
      clinician treated all patients. A Criticare monitor recorded the following at 5
      minute intervals: (1) O2 saturation; (2) respiratory rate; (3) heart rate; (4)
      systolic and diastolic blood pressures; (5) end tidal carbon dioxide
      concentration; and (6) mean arterial blood pressure. RESULTS: The t test
      indicated significant differences between the 2 regimens for: (1) heart rate; (2)
      systolic blood pressure; and (3) diastolic blood pressure (regimen II had higher
      values). Using the general linear model, no significant differences were found.
      All cardiopulmonary parameters were within normal limits. CONCLUSION: Regimens I
      and II had similar cardiopulmonary effects.

PMID- 16903446
TI  - A comparison of 3 routes of flumazenil administration to reverse benzodiazepine
      induced desaturation in an animal model.
AB  - PURPOSE: The purpose of this study was to examine intralingual (IL) and
      submucosal (SM) delivery offlumazenil as viable alternatives to immediate
      intravenous (IV) administration for reversing benzodiazepine sedation in an
      animal model. METHODS: A dog animal model was chosen based upon comparable body
      weight to children (12-17 kg) and the ease of oral access in this species.
      Research design was a nonrandomized matched pair study. This type of "before-and
      after study" allowed the dogs to receive 3 different routes of flumazenil
      administration (IV, IL, and SM) following an initial dose of midazolam (0.5 mg/kg
      IV). Blood samples were obtained (at 0, 2, 4, 8, 15, and 30 minutes) for high
      performance liquid chromatography (HPLC) analysis of flumazenil and midazolam,
      and oxygen saturation values were recorded. RESULTS: Both IL and SM delivery of
      flumazenil were determined to be viable alternatives to immediate IV
      administration for reversing benzodiazepine-induced oxygen saturation (SaO2)
      desaturation. For flumazenil to be able to reverse the SaO2 desaturation, the
      plasma levels must be greater than 5 ng/ml, which was exceeded by IL and SM drug
      delivery. CONCLUSION: In a benzodiazepine-induced desaturation, the submucosal
      and intralingual routes are viable alternatives to intravenous administration of
      flumazenil in an animal model.

PMID- 16903447
TI  - Comparison of chairside microbiological screening systems and conventional
      selective media in children with and without visible dental caries.
AB  - PURPOSE: The purpose of this study was to compare the results of commercial
      chairside microbial tests (CT) and conventional selective media (GS, gold
      standards) for mutans streptococci (MS) and lactobacilli (LB) using oral
      specimens from young children with and without visible dental caries. METHODS:
      Using cotton swabs to collect oral microbial specimens from children 10 to 36
      months old, microbial counts of CT and GS were compared with caries experience of
      the subjects. Contamination levels by non-MS or non-LB isolates on CT and GS were
      also determined. The CT employed were: (1) CRT bacteria for MS and LB; (2)
      CarioCheck Plus for MS and LB; and (3) Dentocult SM and Mucount for MS. RESULTS:
      All CT and GS for MS represented caries status of the participants (P<.001,
      Fisher exact test; P<.015 linear regression), whereas only GS for LB showed
      significant association with caries status (P<.001, Fisher exact test; P<.001,
      linear regression). Non-MS or non-LB isolates were observed on most media, and CT
      usually exhibited higher contaminant levels than GS. Dentocult SM and Mucount did
      not harbor contaminants. CONCLUSIONS: Despite contamination, CT and GS for MS and
      GS for LB exhibited satisfactory outcomes based on cross-sectional caries
      experience of infants and toddlers.

PMID- 16903448
TI  - Comparison of nutritional counseling between provider types.
AB  - OBJECTIVE: The goal of this study was to compare the provision of and attitudes
      toward nutritional counseling between pediatricians and pediatric dentists.
      METHODS: Questionnaires were mailed to 500 US members of the American Academy of
      Pediatric Dentistry and the American Academy of Pediatrics. RESULTS: The survey
      had a response rate of 33% (pediatric dentists=36%; pediatricians=29%). 84% of
      pediatricians routinely offered nutritional counseling compared to 71% of
      pediatric dentists. With respect to cariogenic foods, 82% of pediatric dentists
      and 74% of pediatricians correctly recommended bottle contents, and 33% of
      pediatric dentists and 19% of pediatricians correctly recommended snacks. 79% of
      pediatric dentists compared to 69% of pediatricians believed nutritional
      counseling had at least some effectiveness. Eighty-nine percent of both
      specialties somewhat or strongly agreed that nutritional counseling was an
      important aspect of oral health care. CONCLUSIONS: While pediatric dentists made
      slightly better recommendations than pediatricians regarding cariogenic foods,
      both provider types demonstrated a need for more education regarding nutritional
      counseling.

PMID- 16903449
TI  - Exploring the association between overweight and dental caries among US children.
AB  - PURPOSE: The purpose of this study was to examine the relationship between age
      specific body mass index (BMI-for-age) and dental caries among US children.
      METHODS: Body measures data and oral health data came from the 1999-2002 National
      Health and Nutrition Examination Survey. Outcome measures for primary and
      permanent dentitions were: (1) dental caries prevalence; and (2) severity
      (geometric mean dft and DMFT). Covariates included: (1) age; (2) gender; (3)
      race/ethnicity; and (4) poverty status. Analysis was limited to children 2 to 17
      years old. RESULTS: Approximately 36% of overweight children 2 to 6 years old and
      39% of overweight children 6 to 17 years old had dental caries. Geometric mean
      dental caries scores for overweight children were dft=3.3 and DMFT=2.5 for
      primary and permanent dentitions, respectively. Controlling for covariates, there
      was no significant association between BMI-for-age and dental caries prevalence
      in either dentition. In addition, among children with a positive history of
      dental caries, BMI-for-age was significantly associated with dental caries
      severity in the permanent dentition - overweight children had a lower geometric
      mean DMFT than did normal weight children. CONCLUSIONS: Although it was
      hypothesized that age-specific body mass index would be associated with increased
      dental caries prevalence and severity, these associations were not found. Rather,
      overweight was found to be associated with lower geometric mean DMFT. Future
      studies should address which factors specific to overweight in children might be
      protective against dental caries in the permanent dentition. Given the importance
      of overweight as a public health problem, however, clinicians are encouraged to
      continue providing health education and dietary counseling to their overweight
      child patients.

PMID- 16903450
TI  - The drugs-violence nexus among Mexican-American gang members.
AB  - This study examines hypotheses and builds models to help clarify the causal
      connections between drugs and violence outcomes among Mexican-American male gang
      members. The study uses cross-sectional data of 160 male gang members sampled
      from 26 gangs in a Southwestern city. A life-history /intensive interview using
      closed and open-ended questions and a violence risk psychometric test (PFAV) also
      employed 10 scenario questions to elicit self-produced accounts of the
      participant's last fight. Gang member participant's ages ranged from 14 to 25
      years with a mean age of 18.5 years. The study concludes that drug use interacts
      with an individual gang member's risk for violence to affect violent behavior
      outcomes. Furthermore, an important situational variable explaining violent
      outcomes among respondents scoring high on the violence risk measure was whether
      the rival was using drugs that resulted in high intoxication levels. The study
      concludes that drugs have a modulating and mediating influence on violence that
      is conditioned by situational and individual level variables among members of
      these adolescent street gangs.

PMID- 16903451
TI  - Drug users' participation in addiction care: different groups do different
      things.
AB  - This study allocated 201 (nearly) daily users of heroin and/or crack into four
      groups, depending on their addiction care participation. Earlier studies have
      compared treatment groups and nontreatment groups. In this study the treatment
      group is divided into three categories: (1) drug users in contact with only
      treatment agencies--i.e., methadone maintenance, clinical and ambulant drug
      treatment; (2) drugs users in contact with only care agencies--i.e., day and
      night shelters and drug consumption rooms, which have no explicit aims to change
      patterns of drug use; and (3) drug users in contact with both treatment and care
      agencies. This allocation intro three different groups fits the notion of harm
      reduction, one of the policy aims in The Netherlands. The fourth group consists
      of drug users in contact with neither treatment nor care agencies. The results
      show that it is useful to distinguish these four categories, instead of two. The
      four groups are different from each other with respect to some of their
      characteristics (e.g. debt situation, prostitution, homelessness) and their drug
      use (e.g. drug use in public, use of crack, and use of other drugs). A much
      clearer distinction can be made between the "care" group and the "treatment and
      care" group. Treatment and care agencies can thus better match their services to
      their clients or patients.

PMID- 16903452
TI  - Are Americans receptive to smokefree bars?
AB  - It is not known whether the American public accepts smokefree bars and
      restaurants. Anticipating public displeasure with these ordinances, tobacco,
      liquor and restaurant industry trade associations have helped to stall efforts to
      pass laws curbing bar and restaurant smoking in the expectation that diminished
      patronage would inevitably result. This cross-sectional trend study uses data
      from the May 1993 and January 1999 Current Population Surveys, Tobacco Use
      Supplements to compare tobacco-control attitudes among American bar and
      restaurant workers, all other workers, smokers and nonsmokers (total n = 90,661).
      It was found that by 1999, smokefree workplaces were widely accepted by two
      thirds of adults, with half favoring completely smokefree restaurants. Completely
      smokefree bars remained less popular, with nearly equal numbers (about 30%)
      preferring them or favoring unrestricted bar smoking. Even among bar and
      restaurant industry workers less than 10% favored unrestricted restaurant
      smoking. Greater acceptances of smokefree bars are now taking hold, especially in
      places like California, where acceptance rose 15% in six years, and 45% preferred
      them. Opponents to smokefree bars and restaurants may have underestimated the
      levels of support and growing acceptance of smokefree living areas now taking
      hold among the general public.

PMID- 16903453
TI  - Values and beliefs of psychedelic drug users: a cross-cultural study.
AB  - Psychedelic drugs such as LSD and psilocybin are often claimed to be capable of
      inducing life-changing experiences described as mystical or transcendental,
      especially if high doses are taken. The present study examined possible enduring
      effects of such experiences by comparing users of psychedelic drugs (n = 88),
      users of nonpsychedelic illegal drugs (e.g., marijuana, amphetamines) (n = 29)
      and non illicit drug-using social drinkers (n = 66) on questionnaire measures of
      values, beliefs and emotional empathy. Samples were obtained from Israel (n =
      110) and Australia (n = 73) in a cross-cultural comparison to see if values
      associated with psychedelic drug use transcended culture of origin. Psychedelic
      users scored significantly higher on mystical beliefs (e.g., oneness with God and
      the universe) and life values of spirituality and concern for others than the
      other groups, and lower on the value of financial prosperity, irrespective of
      culture of origin. Users of nonpsychedelic illegal drugs scored significantly
      lower on a measure of coping ability than both psychedelic users and non illicit
      drug users. Both groups of illegal drug users scored significantly higher on
      empathy than non illicit drug users. Results are discussed in the context of
      earlier findings from Pahnke (1966) and Doblin (1991) of the transformative
      effect of psychedelic experiences, although the possibility remains that present
      findings reflect predrug characteristics of those who chose to take psychedelic
      drugs rather than effects of the drugs themselves.

PMID- 16903454
TI  - Suicidal ideation in veterans receiving treatment for opiate dependence.
AB  - Persons with opiate use disorders, especially veterans, have a number of both
      chronic and acute indicators of risk for suicide, but are not typically screened
      for suicidal ideation on a routine basis, beyond initial evaluations. One hundred
      one veterans receiving treatment for opiate dependence at an urban VA medical
      center were screened for suicidal ideation. Over 24% reported some suicidal
      ideation. Current ideation was associated with severe chronic pain, ongoing
      problems with street drugs, firearm ownership, and with having recently enrolled
      in treatment. It was also associated with a variety of recent negative life
      events and mental health issues, especially depression, recurring troubling
      thoughts, hallucinations, loss of jobs, and conflicts with family members. Two
      veterans endorsing suicidal ideation required immediate hospitalization. The
      implications of these findings are discussed, and frequent screening for suicidal
      ideation among patients receiving treatment for opiate dependence is recommended.

PMID- 16903455
TI  - Maintaining the viability and safety of the methadone maintenance treatment
      program.
AB  - The purpose of this article is to describe a methadone maintenance treatment
      (MMT) program and address how such programs can maintain their viability in the
      community as well as the safety of the clinic environment for patients and staff.
      The complex nature of the MMT patient is described including social, legal and
      psychiatric issues. Diversion (selling of methadone) is discussed and examples of
      how to combat diversion are explored, including monitoring of take-home
      privileges. The safety of the clinic setting may be ensured through the
      utilization of toxicology screens and breathalyzers as well as through limit
      setting, enforcement of program rules and the maintenance of professional
      therapeutic boundaries.

PMID- 16903456
TI  - Street-level effects of local drug policy on marginalization and hardening: an
      ethnographic study among chronic drug users.
AB  - This study focuses on the effects of increased enforcement on marginalization of
      and quality of relations between chronic drug users in the region of Parkstad
      Limburg (The Netherlands). Data were mainly gathered by ethnographic community
      fieldwork, verified by interviews with key informants and supported by a survey
      sample of 100 drug users. The results show direct effects of repression on
      stigmatization and marginalization of drug users, and on the availability of
      drugs. More indirect effects are the hectic reactions of drug users and dealers,
      greater visibility of drug users in public places, and increased tensions in and
      deterioration of relations between the drug users. The impact of the increased
      enforcement on reports of drug-related nuisance in general population surveys and
      on police control is also discussed.

PMID- 16903457
TI  - A select annotated bibliography: illegal drug research in rural and suburban
      areas.
AB  - As the diffusion of illegal drugs continues to spread to rural and suburban
      areas, there is a greater need among illegal drug researchers, law enforcement,
      and policy makers to gain knowledge from previous work done on what is loosely
      termed as rural substance abuse research. To help serve that need an annotated
      bibliography is proffered based on three categories and one method of illegal
      substance abuse research. These are: drug consumption, drug distribution, drug
      prices, and ethnography. An exhaustive review of the literature was not
      undertaken, but rather a focus on research that addresses drug consumption and
      distribution is put forward.

PMID- 16903458
TI  - A treatment model for craving identification and management.
AB  - This article presents an addiction treatment model based on craving
      identification and management (CIM). Craving is broadly defined as the desire to
      use alcohol or other drugs; it increases the likelihood of use of these
      substances. In the CIM Model treatment interventions are referenced to craving,
      i.e., helping clients to identify their craving level and equipping them with
      strategies to avoid use. Four causes of craving are identified: (1) environmental
      cues (triggers): exposure to people, places, and things associated with prior
      drug-using experiences may cause immediate and overwhelming craving; (2) stress:
      addicted persons experience stress as craving; (3) mental illness; and (4) drug
      withdrawal: symptoms of both mental illness and withdrawal lead to craving if
      clients associate use with relief of these symptoms. The CIM Model incorporates
      four service delivery elements: Relapse Prevention Workshop, individual
      counseling, medical/psychiatric services, and screening for ongoing drug use. At
      its core, the CIM Model asks clients to be aware of craving, analyze its causes,
      and, based on those causes, implement specific strategies to prevent and manage
      craving. The CIM Model combines several treatment components, including control
      of exposure to environmental cues, establishment of a daily schedule, the use of
      behaviors that dissipate craving (tools), and treatment (with medications when
      appropriate) of mental health and withdrawal symptoms. The CIM Model is a client
      derived approach to achieving and maintaining sobriety based on a process of
      analyzing craving and managing it with an individualized program of recovery
      activities.

PMID- 16903459
TI  - Case-control retrospective study of pulmonary tuberculosis in heroin-abusing
      patients in China.
AB  - The objective of this study was to observe the clinical significance of pulmonary
      tuberculosis in heroin abusers. A case-retrospective study was done to analyze
      clinical symptoms and severity based on chest X-rays, results of sputum bacterial
      test and effects of treatment. The clinical symptoms in patients with
      tuberculosis and heroin addiction were more severe than those in the nonheroin
      addicted group. An examination of chest X-rays showed that tuberculosis lesions
      were involved in two or more lung fields in 80% of the heroin-addicted cases. In
      73.3% of the cases, sputum bacterial tests were positive for tuberculosis. After
      anti-tuberculosis treatment, chest X-rays showed a recovery rate of 46.67%, caves
      became smaller by 41.7%, and the sputum negative conversion rate was 45.5%. There
      are significant differences compared with the control group (p < 0.05). The
      patients with pulmonary tuberculosis combined with heroin addiction had more
      severe clinical symptoms, more lesion zones found in their chest X-rays, higher
      sputum tuberculosis positive rates, and poorer treating effects.

PMID- 16903461
TI  - The effect of feed deprivation on tissue invasion by Salmonella enteritidis.
AB  - A tissue culture procedure was utilized to compare tissue cell invasion by
      Salmonella enteritidis from molted and full feed hens. Three identical trials
      were performed in which 80-wk-old active laying hens were divided into 2 groups
      of 6 birds each. The molted hen group was subjected to a 14-d feed withdrawal,
      and the full-fed hen group was administered a standard layer ration. After feed
      treatment, crop, ileum, cecum, and ovary (small and large yellow follicles
      removed) were collected, rinsed in PBS, and placed into 50 mL of RPMI medium. The
      ends of intestine and crop tissues were tied to allow attachment of Salmonella
      only to the lumen surface. The RPMI medium containing 10(7) to 10(8) cfu of
      novobiocin and nalidixic acid-resistant phage type 13 Salmonella enteritidis was
      injected into the lumen of the intestine and crop tissues. Additionally, ovaries
      were incubated in 50 mL of RPMI medium containing 10(6) to 10(7) cfu of the
      Salmonella enteritidis. Tissues were incubated with Salmonella at 37 degrees C
      for 2 h, after which tissues were placed in 50 mL of fresh RPMI medium containing
      500 microg/mL of gentamicin and incubated for 5 h at 37 degrees C to remove any
      Salmonella that had not penetrated tissues. Tissues were rinsed, stomached in 10
      mL of PBS, serially diluted, and plated onto brilliant green agar containing
      novobiocin and nalidixic acid for Salmonella enumeration. Salmonella invasion of
      ovaries was reduced in tissues from molted hens in trials 1 and 2 as compared
      with full-fed controls (> 1.2 log reduction) but not in trial 3. Salmonella
      invasion of ceca from molted hens was numerically increased in trials 1 and 2 and
      significantly increased in trial 3 as compared with controls (> 0.8 log
      increase). No significant differences in Salmonella invasion were detected for
      crops and ileum. These data suggest that molting may affect invasion of tissues
      by Salmonella enteritidis.

PMID- 16903460
TI  - A comparison between instant and laboratory oral fluid analysis among arrestees.
AB  - Research studies that collect biological measures of drug use have traditionally
      utilized laboratory urinalysis. Several recent studies have also documented the
      utility of laboratory oral fluid (OF) analysis. A new method of drug testing
      instant OF technology--may offer a quicker, equally accurate alternative to
      laboratory OF assays. To date, however, no field studies have compared the two
      methods. In the current study, an instant OF test (ORALscreen) was administered
      to 65 adult arrestees surveyed through Maryland's Substance Abuse Need for
      Treatment among Arrestees (SANTA) study. Following a research interview, a second
      OF sample was collected (ORALconfirm) and shipped to the manufacturer's
      laboratory for analysis. The instant OF test was 96% sensitive and 83% specific
      for cocaine, 100% sensitive and 75% specific for opiates, and 100% sensitive and
      94% specific for marijuana. Kappa statistics were low for all three drugs,
      suggesting poor agreement between the two tests. Moreover, while the marijuana
      sensitivity and specificity coefficients in the current study were high, a
      growing body of research has indicated that OF analysis is not as accurate as the
      gold standard of urinalysis in detecting recent marijuana use. Implications for
      these findings are discussed.

PMID- 16903462
TI  - Antibody response of chickens to sheep red blood cells: crosses among divergently
      selected lines and relaxed sublines.
AB  - Crosses were made among lines of chickens that had undergone 30 generations of
      selection for high or low antibody response 5 d after an intravenous injection
      with SRBC, and between sublines in which selection was relaxed in generation 24.
      Antibody responses at 5, 10, and 14 d after injection were measured in the 4
      lines and in reciprocal crosses among them. Divergence between the high and low
      lines selected for SRBC antibody was immediate and increased during selection.
      Although significant in both cases, separation of the relaxed subline from its
      respective selected line was greater in the high than the low line. Five-day SRBC
      titers of the relaxed lines and the crosses were intermediate to the high and low
      selected lines, with the direction and magnitude of heterosis being line
      dependent. A high proportion of chickens from low line mating combinations did
      not have detectable antibody titers at 10 and 14 d postinoculation with SRBC,
      precluding statistical analysis of these data. Results are discussed in the
      context of intra- and interlocus effects on the selected trait.

PMID- 16903463
TI  - Foot pad dermatitis and hock burn in broiler chickens and degree of inheritance.
AB  - A total of 2,118 birds from 2 strains were allocated to 12 groups of 93 to 100
      each in 2 time-separated replicates. The development of foot pad dermatitis (FPD)
      and hock burn (HB) were recorded weekly from d 8 to slaughter on a set sample of
      live animals (7 per group). In addition, feet and hocks of all birds were
      investigated at slaughter at either 4, 6 (fast-growing strain), 8, or 10 (slow
      growing strain) wk of age. Lesions were scored for both the left and right foot
      and classified according to a scale from 1 (no lesion) to 9 (very severe lesions)
      for FPD and from 1 (no lesion) to 3 (very severe lesions) for HB. No FPD lesions
      and very few low-grade HB lesions were found in chickens from the slow-growing
      strain. In the fast-growing strain, the first signs of FPD and HB were seen in wk
      2. The incidence of both types of lesions increased thereafter. Foot pad
      dermatitis was more frequent in females (49 vs. 36%, P < 0.05). Body weight did
      not affect FPD, but more HB were found at higher BW (P < 0.01). Egg weight
      influenced neither FPD nor HB. Variance and covariance components were analyzed
      using a multivariate animal model, in which scores for FPD and HB were
      transformed into logarithmic scale. The analyses were carried out using
      restricted maximum likelihood algorithm. Heritabilities were estimated to be 0.31
      +/- 0.12 (SE) for FPD, 0.08 +/- 0.08 for HB, and 0.38 +/- 0.13 for BW. Genetic
      correlations among these traits were low and nonsignificant. Phenotypic
      correlation between BW and FPD was low and nonsignificant and between BW and HB
      was 0.17 +/- 0.05 (P < 0.01). The relative high heritability of FPD and the low
      genetic correlation to BW suggested that genetic selection against susceptibility
      to FPD should be possible without negative effects on BW gain.

PMID- 16903464
TI  - Variation in the pulmonary hypertensive responsiveness of broilers to
      lipopolysaccharide and innate variation in nitric oxide production by mononuclear
      cells.
AB  - Variability among broilers in their pulmonary hypertensive (PH) responsiveness to
      lipopolysaccharide (LPS) appears to reflect innate variation in the types or
      proportions of vasodilators and vasoconstrictors released by leukocytes and
      endothelial cells. Two experiments were designed to evaluate possible
      correlations between the PH responsiveness to LPS in vivo and the quantities of
      nitric oxide (NO; a potent pulmonary vasodilator) produced by mononuclear cells
      in vitro. In Experiment 1, blood samples were collected from male broilers from a
      base population (control group) and from survivors of a 60% lethal dose i.v.
      injection of cellulose microparticles (MP survivor group). In Experiment 2, blood
      samples were collected from male broilers from a relaxed line and from lines
      known to be susceptible or resistant to pulmonary hypertension syndrome.
      Peripheral mononuclear cells (PMNC) from each blood sample were cultured at 2
      million cells per well, remained unstimulated, or were stimulated with LPS to
      elicit the expression of inducible NO synthase, and the 24-h production of NO was
      measured. In both experiments, unstimulated PMNC cultures did not produce
      consistently detectable levels of NO, whereas LPS-stimulated cultures produced
      quantities of NO that varied widely among individuals. Nitric oxide production by
      cultured PMNC also was evaluated by flow cytometry, demonstrating that LPS
      stimulated PMNC produced substantially more NO than did unstimulated cells in all
      of the groups evaluated. Moreover, NO-producing PMNC were identified to be
      monocytes. The same broilers from which PMNC had been isolated were catheterized
      subsequently to record pulmonary arterial pressure, LPS was injected i.v. to
      assess the amplitudes of peak and postpeak PH responses, then N(omega)-nitro-L
      arginine methyl ester was injected to inhibit ongoing NO production. In
      Experiment 1, the amplitude of the peak and postpeak PH responses to LPS were
      correlated with the quantity of NO produced by LPS-stimulated cultured PMNC from
      broilers in the control group but not for MP survivors. In Experiment 2, the
      postpeak PH response to LPS was correlated with the quantity of NO produced by
      LPS-stimulated PMNC from broilers in the relaxed line, but not in the susceptible
      or resistant lines. In all groups, N(omega)-nitro-L-arginine methyl ester
      injections triggered substantial increases in pulmonary arterial pressure (> or =
      8 mm Hg), thereby revealing a significant ongoing modulation by NO of the PH
      response to LPS. We concluded that most of the modulatory NO generated in vivo
      during the acute PH response to LPS (within 60 min postinjection) likely is
      produced by constitutive NO synthase in the vascular endothelium. In addition,
      the NO produced by inducible NO synthase in PMNC appeared to have modulated the
      LPS-stimulated PH responses of unselected broilers having the broadest range of
      pulmonary vascular capacities (control broilers and relaxed line), but not in
      broilers whose pulmonary vascular capacities had been selected to represent the
      higher (MP survivors, resistant line) or lower (susceptible line) extremes of the
      population.

PMID- 16903465
TI  - Maternal antibody transfer from dams to their egg yolks, egg whites, and chicks
      in meat lines of chickens.
AB  - Maternal antibodies are transferred from hens to the chicks via the egg. To gain
      insight into maternal antibody transfer and endogenous production of antibodies
      in broiler chicks, total IgY, IgA, IgM, as well as anti-Newcastle disease virus
      (NDV) and anti-infectious bronchitis (IBV) antibody levels were examined in the
      dams' plasma, egg yolks, egg whites, and chicks' plasma on d 3, 7, 14, and 21.
      Blood was collected from 39-wk-old breeder hens (line 1, n = 17; line 2, n = 21).
      Fertile eggs were used for antibody extraction from the egg yolks and egg whites
      (4 to 5 eggs/dam) and for hatching. Unvaccinated chicks (4 to 5 chicks/dam) were
      reared in a HEPA-filtered room and were bled on d 3, 7, 14 and 21. Based on ELISA
      methods, plasma levels of IgY and IgM were higher (P < 0.0001), and those of IgA
      were similar (P = 0.31), in line 2 compared with line 1. Egg yolk IgY and IgA, as
      well as egg white IgY, IgA, and IgM levels were higher in line 2 compared with
      line 1 (P < 0.0001). Independent of line of chicken, the percentage dam-to-chick
      (3 d) plasma transfer of IgY was estimated to be approximately 30%, with that for
      IgM and IgA less than 1%. Chicks synthesized IgM first, followed by IgA and IgY.
      Anti-NDV and anti-IBV antibodies were detected in the dams' plasma, egg yolks,
      and in the chicks' plasma on d 3 and 7, with line 2 having higher anti-IBV and
      lower anti-NDV levels than line 1 in all samples (P < 0.0001). In summary, IgY
      levels, total or antigen-specific, in the dams' plasma or eggs were found to be a
      direct indicator of maternal antibody transfer to the chicks' circulation, with
      an expected percentage transfer of approximately 30%. This knowledge, together
      with the observed time course of endogenous antibody production in broiler
      chicks, may find direct application in formulating strategies for protecting
      chicks, especially during the first few weeks of age when their immune system is
      not yet fully functional.

PMID- 16903466
TI  - Evaluation of the influence of bacteriophage titer on the treatment of
      colibacillosis in broiler chickens.
AB  - Two studies were conducted to determine the efficacy of bacteriophage SPR02 and
      DAF6 at varying titers to treat colibacillosis in chickens. In Study 1, the
      treatments consisted of a control, i.m. injection of bacteriophage SPR02 or DAF6,
      Escherichia coli airsac challenge, and E. coli challenge followed by treatment at
      different titers with bacteriophage SPR02 or DAF6. The E. coli- challenged birds
      were injected with 6 x 10(4) cfu into the left thoracic airsac at 7 d of age.
      Immediately after the birds were challenged with E. coli, they were treated by
      administration of bacteriophage SPR02 or DAF6 by i.m. injection into the left
      thigh with 4 x 10(8), 10(6), 10(4), or 10(2) pfu. Study 2 was identical to Study
      1, with the exception that the E. coli challenge was increased to 9 x 10(4) cfu,
      and the titers of SPR02 and DAF6 were slightly less at 3 x 10(8), 10(6), 10(4),
      and 10(2) pfu. Both studies were concluded when the birds were 3 wk of age.
      Mortality in the birds challenged with E. coli in Studies 1 and 2 was 48 and 47%,
      respectively. The only consistently effective bacteriophage treatment was the
      highest titer (10(8) pfu) of bacteriophage SPR02, which significantly reduced
      mortality from 48 and 47% in the birds only challenged with E. coli (positive
      control) to 7% in both studies, which was not significantly different from the
      unchallenged negative control treatments. These studies indicate that an
      effective multiplicity of infection for i.m. treatment with SPR02 was 10(4) in
      this experimental model of colibacillosis. Bacteriophage administered at
      sufficient titers can be effective therapeutic agents and provide an alternative
      to antibiotics in the treatment of bacterial diseases.

PMID- 16903467
TI  - Detection of Campylobacter jejuni in various lymphoid organs of broiler breeder
      hens after oral or intravaginal inoculation.
AB  - Two studies were conducted to determine whether Campylobacter jejuni could
      rapidly spread and reside in the internal organs of adult broiler breeder hens.
      In Study 1, university-housed broiler breeders at 22 wk of age were obtained and
      placed in individual cages. Each hen was intravaginally inoculated weekly from 23
      to 32 wk of age with a characterized strain of C. jejuni. At wk 23, 27, and 32, 4
      d postinoculation, the hens were euthanized, defeathered, and aseptically opened.
      In Study 2, university-housed broiler breeder hens were obtained at 42, 53, and
      56 wk of age, placed in individual cages, and inoculated either orally or
      intravaginally with a characterized strain of C. jejuni. To reduce the
      possibility of cross-contamination among samples, the thymus, spleen, liver, and
      gallbladder were aseptically removed, prior to the ceca. In both studies, all
      samples were individually analyzed. In Study 1, at 23 wk of age, C. jejuni was
      recovered from 4/7 thymii, 2/7 spleens, 5/7 livers and gallbladders, and 6/7
      ceca. At 27 wk of age, C. jejuni was recovered from 1/7 thymii and 1/7 ceca. At
      32 wk of age, C. jejuni was recovered from 4/11 thymii, 1/11 livers and
      gallbladders, and 2/11 ceca. In Study 2, C. jejuni was recovered from 2/6 thymii
      and 5/6 ceca after oral inoculation and 1/6 spleens, 1/6 livers and gallbladders,
      and 4/6 ceca after vaginal inoculation of 43-wk-old hens. Campylobacter jejuni
      was recovered from 2/5 thymii, 3/5 spleens, 3/5 livers and gallbladders, and 2/5
      ceca after oral inoculation of 53-wk-old hens and 1/5 thymii and 1/5 livers and
      gallbladders after vaginal inoculation. Campylobacter jejuni was recovered from
      1/4 thymii, 2/4 livers and gallbladders, and 1/4 ceca and was not detected in any
      vaginally inoculated birds of 57-wk-old hens. This study provides evidence that
      C. jejuni can reside in the internal organs of broiler breeder hens following
      oral or intravaginal inoculation.

PMID- 16903468
TI  - Mortality and growth performance of broilers given drinking water supplemented
      with chicken-specific probiotics.
AB  - For application in broiler production, we developed a multispecies (MSPB) and a
      chicken-specific (CSPB) probiotic preparation in fluid form. The MSPB contained
      different probiotic species of human origin, whereas the CSPB consisted of 7
      Lactobacillus species isolated from the digestive tract of chickens. In a field
      trial with broilers, MSPB treatment resulted in a slight increase (by 1.84%) in
      broiler productivity based on an index taking into account daily weight gain,
      feed efficiency, and mortality. The CSPB treatment reduced mortality in 2
      subsequent field trials and raised productivity by 2.94 and 8.70%. In a
      controlled trial with broilers showing a high index of productivity, probiotic
      treatment further raised productivity by 3.72%. Based on the present 4 studies in
      combination with 9 studies published earlier, it is suggested that with higher
      productivity rates of the broilers the effect of probiotics becomes smaller.

PMID- 16903469
TI  - Supplementation of corn-soy-based diets with an Eschericia coli-derived phytase:
      effects on broiler chick performance and the digestibility of amino acids and
      metabolizability of minerals and energy.
AB  - The effect of the supplementation of diets containing low available P
      concentrations with low and supra-activities of an Eschericia coli 6-phytase was
      assessed using growing broiler chicks. A total of 384 female Ross broiler chicks
      were weighed at d 1 of life and assigned to 1 of 8 experimental treatments. There
      were 12 replicate cages with 4 chicks per cage, and the diets were fed from d 1
      of life for a period of 16 d. A positive control diet (5 g/kg of available P) and
      a negative control diet (3 g/kg of available P) were used, and 6 more diets were
      manufactured by supplementing the negative control diet with 150, 300, 600,
      1,200, 2,400, and 24,000 U/kg of exogenous phytase. Body weight gain and feed
      conversion ratios were determined, as were nutrient digestibility coefficients
      and toe ash values. Birds fed the negative control diet had lower (P < 0.05)
      weight gains than those fed the positive control diet. The addition of exogenous
      phytase above 150 U/kg improved (P < 0.05) weight gain, toe ash percentage, and
      nutrient utilization of the birds fed the negative control diet. Furthermore, the
      24,000 U/kg of diet improved (P < 0.05) toe ash percentage and the utilization of
      several nutrients beyond that of the lower doses of phytase. It can be concluded
      that the supplementation of diets containing 3 g/kg of available P with exogenous
      phytase can improve the performance of chicks to that of birds fed a diet
      containing 5 g/kg of available P. In addition, the use of high doses of phytase
      (> 1,000 U/kg of diet) can improve nutrient availability in poultry diets beyond
      that of diets containing lower (< 1,000 U/kg) phytase activities. These results
      may be mediated partially by reduced endogenous loss as well as an increase in
      the availability of dietary nutrients as indicated by improvements in
      digestibility coefficients.

PMID- 16903470
TI  - Concentrations of putrescine, spermidine, and spermine in duodenum and pancreas
      as affected by the ratio of arginine to lysine and source of methionine in
      broilers under heat stress.
AB  - An experiment was designed to investigate the effect of Arg, Lys, Met, and
      environmental temperature on broiler performance and associated changes in
      duodenal and pancreatic polyamines. Two groups of 26-d-old Ross male broilers
      raised under thermoneutral (TN) conditions were reallocated to 4 rooms kept at
      heat stress (HS) or TN. Birds were fed equimolar amounts of 2-hydroxy-4
      (methylthio) butanoic acid (HMB) or DL-Met (DLM) at requirement levels with
      Arg:Lys at 0.95 or 1.40. Twelve replicates of 4 birds were offered each diet ad
      libitum. Body weight gain, efficiency of dietary CP accretion (CPE), feed intake,
      and feed conversion ratio were ascertained from 26 to 33 d and from 34 to 47 d of
      age. One bird per cage was killed at 33 and 47 d, and samples of duodenum and
      pancreas were assayed for putrescine, spermidine, and spermine (Spm), together
      with estimates of duodenal villus height. From 26 to 33 d, birds fed HMB
      performed better than those fed DLM, but only at TN conditions. From 34 to 47 d,
      feeding HMB tended to optimize CPE when added to diets high in Arg. However,
      lower CPE was obtained when HMB was added to low-Arg diets, whereas birds fed DLM
      were unaffected by these treatments (P < 0.10). Methionine source, Arg:Lys, or
      both affected the concentrations of duodenal and pancreatic polyamines, with some
      changes correlating with performance variables during HS (P > 0.05). It was found
      that HS caused lower tissue spermidine (P < 0.001) and higher pancreatic Spm (P =
      0.08) from 34 to 47 d. Putrescine concentrations were affected by diet and HS,
      depending on tissue and experimental period. Pancreatic Spm correlated negatively
      with changes in CPE influenced by Arg:Lys by Met source interaction in
      chronically heat-stressed birds. The possible association between polyamine
      metabolism and some of the effects of the Arg:Lys by Met source interaction
      observed in chronically stressed birds deserves further investigation.

PMID- 16903471
TI  - Evidence for 2-hydroxy-4(methylthio) butanoic acid and DL-methionine having
      different dose responses in growing broilers.
AB  - The objective of this study was to compare the gain-response curve to dietary
      levels of 2-hydroxy-4(methylthio) butanoic acid (HMTBA) and DL-Met (DLM) across 4
      floor pen trials in which different diets were used. Six replicates of 38 or 41
      birds per pen (trials 1 to 2 and 3 to 4, respectively) were used in a 2 x 3
      factorial arrangement. A control with 12 replicates was also included. The 2 Met
      sources were fed at 3 equimolar levels equally spaced, with the highest level
      added at requirements from 1 to 48, 49, 43, or 49 d for trials 1, 2, 3, and 4,
      respectively. Commercial-type TSAA-deficient control diets contained sorghum,
      wheat, corn, or corn plus meat and bone meal for trials 1, 2, 3, and 4,
      respectively. Performance improved at all times for most parameters after
      supplementing with HMTBA or DLM (P < 0.05). No differences were found in the
      birds fed HMTBA or DLM at any age and trial (P > 0.05), except for trial 1, in
      which 17-d-old birds performed better when fed HMTBA than DLM (P < 0.05). In each
      trial, linear, quadratic, and exponential regressions were conducted upon the
      gain response of birds fed HMTBA and DLM separately. Equations with better
      goodness of fit were used to compare the estimated gain responses to feeding
      HMTBA vs. DLM. In 3 trials, the shape of the gain-response curve differed when
      feeding HMTBA vs. DLM. In trials 3 and 4, feeding HMTBA at commercial levels
      resulted in greater gain responses than DLM (P < 0.05), whereas, in trials 2 and
      4, at very deficient levels, DLM-fed birds outperformed those fed HMTBA (P <
      0.05). When the 4 trials were combined, the dose-response curve with the best
      goodness of fit was linear for HMTBA and quadratic for DLM. It can be concluded
      that the 2 Met sources have a different dose-response form, HMTBA could
      outperform DLM at commercial levels, and DLM could outperform HMTBA at deficient
      levels.

PMID- 16903473
TI  - Levels of beta-mannan in soybean meal.
AB  - Beta-mannan, also known as beta-galactomannan, is found in a number of feed
      ingredients for poultry. Of these, soybean meal (SBM) is by far the most commonly
      used, being the primary source of protein in poultry feeds in most countries.
      Although beta-mannan has clearly been shown to be deleterious to poultry and
      animal performance, a survey of its concentration in SBM has yet to be reported.
      Thirty-six samples of SBM, identified as either dehulled or nondehulled, were
      obtained from commercial sources in a number of countries and assayed for beta
      mannan content. Results confirmed that all samples of SBM assayed contained at
      least 1.0% beta-mannan and that concentrations are higher in nondehulled (1.61 +/
      0.20%) than in dehulled samples (1.26 +/- 0.14%).

PMID- 16903472
TI  - Estimation of nitrogen maintenance requirements and potential for nitrogen
      deposition in fast-growing chickens depending on age and sex.
AB  - Experiments were conducted to estimate daily N maintenance requirements (NMR) and
      the genetic potential for daily N deposition (ND(max)T) in fast-growing chickens
      depending on age and sex. In N-balance studies, 144 male and 144 female chickens
      (Cobb 500) were utilized in 4 consecutive age periods (I: 10 to 25 d; II: 30 to
      45 d; III: 50 to 65 d; and IV: 70 to 85 d). The experimental diets contained high
      protein soybean meal and crystalline amino acids as protein sources and 6 graded
      levels of protein supply (N1 = 6.6%; N2 = 13.0%; N3 = 19.6%; N4 = 25.1%; N5 =
      31.8%; and N6 = 37.6% CP in DM). The connection between N intake and total N
      excretion was fitted for NMR determination by an exponential function. The
      average NMR value (252 mg of N/BW(kg)0.67 per d) was applied for further
      calculation of ND(max)T as the threshold value of the function between N intake
      and daily N balance. For estimating the threshold value, the principle of the
      Levenberg-Marquardt algorithm within the SPSS program (Version 11.5) was applied.
      As a theoretical maximum for ND(max)T, 3,592, 2,723, 1,702, and 1,386 mg of
      N/BW(kg)0.67 per d for male and 3,452, 2,604, 1,501, and 1,286 mg of N/BW(kg)0.67
      per d for female fast-growing chickens (corresponding to age periods I to IV)
      were obtained. The determined model parameters were the precondition for modeling
      of the amino acid requirement based on an exponential N-utilization model and
      depended on performance and dietary amino acid efficiency. This procedure will be
      further developed and applied in the subsequent paper.

PMID- 16903474
TI  - Effect of egg turning angle and frequency during incubation on hatchability and
      incidence of unhatched broiler embryos with head in the small end of the egg.
AB  - The effect of turning angle (from vertical) and the interaction with turning
      frequency during incubation on fertile hatchability, embryonic mortality, and the
      incidence of embryos with head in the small end of the egg (malpositioned) was
      studied in 2 experiments comprising 2 trials each to determine if a turning angle
      of less than 45 degrees could be successful. Hatching eggs from commercial
      broiler breeder flocks from 55 to 61 wk of age were utilized, and turning was for
      18 d. Eggs were subjected to turning angles of 35, 40, or 45 degrees, with a
      turning frequency of 24 times daily (24x) in Experiment 1. Turning angle had no
      effect on fertile hatchability. However, the incidence of separately enumerated,
      malpositioned embryos was increased by the 35 degrees angle, compared with both
      the 40 and 45 degrees angles in Experiment 1. Eggs were subjected to turning
      angles (from vertical) of 35 degrees, with a turning frequency of either 24x or
      96x daily, or 45 degrees, with 24x turning in the 2 trials of Experiment 2.
      Turning angle and frequency had no effect on fertile hatchability or embryonic
      mortality, but the incidence of separately enumerated, malpositioned embryos was
      increased by the 35 degrees angle with 24x turning, compared with the 35 degrees
      angle with 96x turning, and the 45 degrees angle, with 24x turning, in Experiment
      2. These data demonstrated that the incidence of malpositioned embryos was
      increased by a reduced turning angle, but that this effect was ameliorated by a
      concomitant increase in turning frequency.

PMID- 16903475
TI  - An expressed sequence tag analysis of the chicken reproductive tract
      transcriptome.
AB  - Analysis of the chicken reproductive tract transcriptome is important in
      comparative biology for analysis of reproductive tract development and evolution.
      In addition, molecular analysis of the reproductive tract is important for
      identification of genes affecting fertility in the poultry industry. We sampled
      the chicken reproductive tract (ovary, oviduct, and testis) transcriptome,
      generating 5,328 expressed sequence tags that assembled into 4,518 contigs. We
      identified 475 contigs with no match in the current expressed sequence tag
      databases or in GenBank. The novel contigs included 31 with no match to the
      current assembly of the chicken genome, 119 representing spliced transcripts, and
      309 that were unspliced. More detailed molecular characterization of the 428
      novel contigs present in the assembly will be important to gene discovery and
      annotation of the chicken and other vertebrate genomes.

PMID- 16903476
TI  - Effect of method of delivering nicarbazin to mallards on plasma 4,4'
      dinitrocarbanilide levels and reproduction.
AB  - Nicarbazin (NCZ), a coccidiostat used in the poultry industry, has been developed
      as a contraceptive for resident Canada geese. We tested the efficacy of NCZ as a
      contraceptive using mallards (Anas platyrhynchos) as a model for Canada geese.
      Nicarbazin-treated corn was fed ad libitum for 14 d at 0, 750, 1,000, or 1,500
      ppm. Plasma and egg levels of 4,4'-dinitrocarbanilide (DNC), the active
      anticoccidial component of NCZ, differed among treatment groups in a dose
      response relationship, but plasma levels did not differ between sexes. Nicarbazin
      caused a decrease in egg weight, but there was no effect of NCZ on the numbers of
      eggs laid per female per day. Nicarbazin did not significantly impact bird
      health. An additional trial tested the effect of the method of NCZ delivery on
      plasma DNC levels. Mallards were given NCZ daily for 12 d either by gavage with a
      corn oil suspension, gavage with a water suspension, peroral administration of a
      capsule, or feeding 500 mg of NCZ/kg of pelleted feed ad libitum. The method of
      delivery significantly affected plasma DNC levels, with the highest levels in the
      corn oil suspension group and the lowest levels in the pelleted feed group. This
      is likely due to decreased availability of NCZ in a pellet compared with gavage
      with a suspension or capsule. Mallards receiving 34.2 mg of NCZ/kg of BW when fed
      cracked corn coated with NCZ daily for 14 d had higher plasma DNC levels than
      those obtained by liquid gavage, capsule, or pelleted NCZ feed. For maximum
      effect in the field, NCZ should be coated onto corn. A higher concentration of
      NCZ is needed in pelleted feed to obtain comparable plasma DNC levels to allow
      for the decreased absorption of DNC.

PMID- 16903477
TI  - Effects of feed restriction and realimentation on digestive and immune function
      in the Leghorn chick.
AB  - How regulatory changes of digestive and immune functions of the gut influence
      each other has not been sufficiently studied. We tested for simultaneous changes
      in the digestive physiology and mucosal immune function of the guts of White
      Leghorn cockerel chicks undergoing food restriction and realimentation. Chicks
      were assigned to 1 of 3 groups: control = fed ad libitum 7 to 17 d of age;
      restricted = feed restricted d 12 to 17 (at 2 restriction levels: 54 and 34% ad
      libitum); refed = feed restricted d 7 to 13 and then fed ad libitum d 14 to 17.
      Refed chicks exhibited 1 d of hyperphagy and an increase in apparent digestive
      efficiency following restriction (ANOVA, P < 0.001). Total small intestine mass
      and duodenal maltase activity differed among the groups in the order refed >
      control > restricted, as expected (ANOVA, P < 0.05 for both measures). In
      contrast, there were no significant treatment effects on our measures of gut
      immune structure and function, including bursa mass, spleen mass, and total IgA
      content of intestinal flush samples measured with standard ELISA techniques. The
      results of this study indicated that, during feed restriction and realimentation,
      some features of gut immune function are maintained unchanged in the face of
      regulatory changes that influence digestive functions.

PMID- 16903478
TI  - Potential role of thyroid hormones and prolactin in the programming of
      photorefractoriness in turkey hens.
AB  - The domestic turkey hen is a seasonal breeder, requiring a period of short days
      to establish photosensitivity and a long day length to initiate egg production.
      The reproductive season is then limited by the onset of photorefractoriness (PR),
      which causes a decline, and then termination, of egg laying. In passerine birds,
      PR is programmed early in the reproductive season by the presence of thyroid
      hormones and a long photoperiod. High circulating prolactin (PRL) is thought to
      hasten the onset of PR. In a prior study, we reported that hens destined to have
      PR exhibited lower levels of thyroxine (T4) and PRL at certain points (weeks)
      following photostimulation than did hens destined to remain photosensitive (PS),
      a result opposite to what might be expected. The present study was conducted to
      further explore the possible relationship between circulating hormone levels and
      subsequent PR in the commercial turkey hen at times (days) closer to
      photostimulation than our previous study. Plasma levels of triiodothyronine (T3),
      T4, and PRL were compared in 2 subpopulations of hens identified retrospectively
      after 50 wk of egg production: A group of 17 hens that exhibited PR (mean onset =
      27 wk of photostimulation) and a group of "good" layers that remained PS (mean
      production = 210 eggs/50 wk). Results showed no differences between groups in
      plasma T3 or T4 levels or in the T3:T4 ratio at -6, 0, 1, 3, and 7 d from
      photostimulation. Plasma PRL levels were significantly higher at 8 and 9 wk after
      photostimulation in hens that remained PS vs. those that became PR. We conclude
      that thyroid hormone levels around the time of photostimulation either are not
      actively related to programming of subsequent PR in turkeys or programming for PR
      in the turkey hen occurs later in the reproductive cycle than in passerine birds.
      We further conclude that hens that exhibit PR tend to have lower circulating PRL
      levels early in the reproductive season than hens that remain PS and lay at a
      relatively high rate.

PMID- 16903479
TI  - Efficacy of iron chelators on Campylobacter concentrations in turkey semen.
AB  - Campylobacter is a leading bacterial cause of human foodborne infections in the
      United States. Recent studies suggest that the organism is highly prevalent in
      poultry semen and may contribute to vertical transmission between the breeder hen
      and offspring. Because Campylobacter requires iron for its growth and survival,
      the objective of this study was to determine if the addition of natural and
      synthetic chelators such as ovotransferrin, desferrioxaime, EDTA, or 2,2'
      dipyridyl could reduce or eliminate Campylobacter in turkey semen. In a
      preliminary study without semen, a commercial poultry semen extender was
      supplemented with various concentrations of ovotransferrin, desferrioxaime, EDTA,
      or 2,2'-dipyridyl and inoculated with an average of 10(8) cfu/mL of a wild-type
      Campylobacter coli turkey semen isolate. At 6 and 24 h of storage at 4 degrees C,
      a sample was taken from each treatment group and enumerated for Campylobacter. In
      all 3 trials, Campylobacter was undetectable (< 10(2)) in the commercial poultry
      semen extender supplemented with 20 mg/mL of 2,2'-dipyridyl. There were no
      differences observed in Campylobacter concentrations in the commercial poultry
      semen extender supplemented with ovotransferrin, desferrioxaime, or EDTA compared
      with unsupplemented controls. In a follow-up study, pooled semen samples were
      randomly collected from toms, diluted with a commercial poultry semen extender
      supplemented with 5, 10, or 20 mg/mL of 2,2'-dipyridyl and inoculated with an
      average of 10(8) cfu/mL of a wild-type C. coli turkey semen isolate. At 6 and 24
      h of storage at 4 degrees C, samples were taken from each treatment group,
      enumerated for Campylobacter, and evaluated for sperm viability. In all 3 trials,
      supplementing the commercial poultry semen extender with 20 mg/mL of 2,2'
      dipyryidyl significantly reduced (3 to 4 logs) Campylobacter concentrations when
      compared with the positive controls. Sperm viability was also reduced with this
      treatment, and, therefore, the use of 2,2'-dipyridyl may not be a practical
      treatment for reducing Campylobacter in poultry semen.

PMID- 16903480
TI  - The effect of water extract of sumac (Rhus coriaria L.) and lactic acid on
      decontamination and shelf life of raw broiler wings.
AB  - In an attempt to improve the bacteriological quality and refrigerated shelf life
      of broiler meat, 10-min surface wash treatments with sterile distilled water
      (DW), 8% (wt/vol) water extract of sumac (Rhus coriaria L.) fruits (WES), and 2%
      (vol/vol) lactic acid (LA) were compared by using a broiler wing model. The
      aerobic plate counts (log10 cfu/g) of psychrotrophs, mesophilic aerobes,
      Enterobacteriaceae, coliforms and presumptive fecal coliforms on the samples were
      determined. Immediately after a 10-min decontaminaton, the mean count of all the
      bacterial groups was determined to be 3.9, 2.6, and 1.7 (log10 cfu/g) for DW,
      WES, and LA, respectively. Because the postdecontamination population level of
      psychrotrophs, mesophiles, and Enterobacteriaceae were low in the LA-treated
      group compared to the WES group, an equity between the 2 groups in the point of
      view of the 3 bacterial groups existed at d 10 of cold storage (3 +/- 1 degrees
      C). Shelf life was 7 and 14 d for wings treated with DW and WES, respectively,
      whereas the LA-treated wings did not spoil after 14 d of cold storage (3 +/- 1
      degrees C). Nevertheless, an undesirable pale color and an acidulous odor
      occurred in the LA-treated wings. In contrast, a good color appeared on the WES
      treated wings, which was also superior to the color of the DW-treated wings. Such
      advantages of WES may be important for poultry processors and for consumers.
      However, the immediate decontamination and refrigerated shelf life extension
      potential of WES should be intensively studied in antimicrobial interventions in
      poultry processing plants.

PMID- 16903481
TI  - Effects of various fat sources, alpha-tocopheryl acetate, and ascorbic acid
      supplements on fatty acid composition and alpha-tocopherol content in raw and
      vacuum-packed, cooked dark chicken meat.
AB  - A factorial design was used to study the effects of dietary fat sources (beef
      tallow, fresh and oxidized sunflower oils, and linseed oil), alpha-tocopheryl
      acetate (0 and 225 mg/kg), and ascorbic acid (0 and 110 mg/ kg) supplementation
      on fatty acid composition, as well as on fat and alpha-tocopherol content in
      vacuum-packed raw and cooked meat stored at -20 degrees C. Raw meat fatty acid
      composition was affected by dietary fat sources and tocopheryl acetate
      supplementation. After cooking, meat composition was only affected by dietary fat
      sources. Birds fed linseed oil yielded meat rich in n-3 fatty acids, especially
      linolenic acid, which provides about 20% of the adequate intake for this fatty
      acid. Birds fed sunflower or oxidized sunflower oil produced meat rich in n-6
      fatty acids, whereas those fed beef tallow resulted in meat rich in saturated and
      monounsaturated fatty acids. Raw and cooked dark chicken meat alpha-tocopherol
      content was only affected by tocopherol supplementation. Supplementation with
      alpha-tocopheryl acetate led to alpha-tocopherol-enriched meat, which provides
      about 25% of the recommended dietary allowance. Moreover, this content in vacuum
      packed samples was not modified even after 7 mo of storage at -20 degrees C.

PMID- 16903482
TI  - Effects of dietary functional ingredients and packaging methods on sensory
      characteristics and consumer acceptance of irradiated turkey breast meat.
AB  - Raw and cooked breast patties from turkeys fed 8 different diets [control; 200
      IU/kg of vitamin E (VE); 0.3 mg/kg of Se; 2.5% conjugated linoleic acids (CLA);
      200 IU/kg of VE + 0.3 mg/kg of Se; 200 IU/kg of VE + 2.5% CLA; 0.3 mg/kg of Se +
      2.5% CLA; and 200 IU/kg of VE + 0.3 mg/kg of Se + 2.5% CLA] were treated with 2
      irradiation doses (0 and 1.5 kGy) and 2 packaging methods (vacuum and aerobic).
      Raw and cooked samples from 32 treatments were tested by 8 trained sensory
      panelists for turkey aroma and irradiation off-aroma. Based on the sensory
      scores, the 3 dietary treatments producing the most and the least off-aroma were
      selected and used for a consumer acceptance study. Sensory results of raw meat
      showed that turkey aroma was intense in aerobically packaged meat, whereas
      irradiation off-aroma was intense with vacuum packaging. Raw meats from dietary
      treatments containing CLA (CLA, VE + CLA, Se + CLA, VE + Se + CLA) had greater
      turkey aroma scores, whereas those containing VE (VE and VE + Se) had lower
      scores than the control. Dietary treatments containing VE (VE, VE + Se, VE + Se +
      CLA) significantly lowered (P < 0.05) irradiation off-aroma in raw turkey breast
      meat, whereas CLA increased it, especially when the meats were packaged
      aerobically. In cooked meat, however, irradiation and packaging had no effect on
      turkey meat aroma and irradiation off-aroma. Cooked meat from turkeys
      supplemented with VE (VE and VE + Se) had less (P < 0.05) irradiation off-odor
      than other dietary treatments. Dietary CLA increased the irradiation off-aroma in
      cooked meat, which could not be reduced, even when VE and Se were combined in the
      diet. Irradiation off-aroma of raw meat was not pleasant for most consumers, and
      dietary supplementation of VE and VE + Se improved consumer acceptance of
      irradiated raw meat. For cooked meat samples, consumers preferred both color and
      flavor of irradiated meat to nonirradiated meat.

PMID- 16903483
TI  - Relationship between chick conformation and quality measures with early growth
      traits in males of eight selected pure or commercial broiler breeder strains.
AB  - Current commercial broiler products are derived from the crosses of various
      strains at the primary breeder level. This study investigated chick development,
      yolk utilization, and early growth rate of males from 8 broiler breeder strains.
      These strains were a combination of both specialized and commercial-line
      products. At hatch, 110 male chicks per strain were weighed and wing-banded, and
      chick quality was assessed. Traits included navel condition, hock color, chick
      length, shank length, and abdomen score by abdominal palpation (to evaluate
      residual yolk content on live chicks). At hatch, 50 chicks per strain were
      dissected to assess breast muscling and residual yolk weight. At 2 wk of age, 50
      chicks per strain were dissected to characterize changes in weight, conformation,
      fleshing, and residual yolk content. Chick weight at hatch varied from 40.8 g in
      a heavily growth-selected line to a low of 36.9 g in a commercial strain. The
      mass of residual yolk at hatch ranged from 0.8 to 10.6 g across all chicks
      dissected at hatch. A heavily breast-selected pure-line strain had 5.8 g of
      residual yolk in contrast to the commercial strain that had only 3.0 g. Although
      there were no significant strain differences in abdomen score, this score
      correlated with dissected residual yolk weight (r = 0.50). Shank length and chick
      body length at hatch correlated more strongly with BW on d 14 than did hatch
      weight. This information stresses the importance of evaluating several
      characteristics at hatch to better quantify early chick quality.

PMID- 16903484
TI  - Effect of flock age, cessation of egg turning, and turning frequency through the
      second week of incubation on hatchability of broiler hatching eggs.
AB  - Hatching eggs from commercial broiler breeder flocks at 34 and 37 wk of age
      (young) and at 59 and 61 wk of age (old) were stored for 2 d at 18 degrees C and
      75% RH and then subjected to turning frequencies of 24 or 96 times daily up to 8,
      10, 12, or 14 d of incubation at standard conditions to determine if an increased
      turning frequency would facilitate an early cessation of turning. Turning was
      discontinued after the respective days were completed. Eggs remained in setter
      trays until combined at 18 d to complete hatching in a single machine. The young
      flocks exhibited significantly better fertile hatchability, as expected, but
      there was no overall effect due to differences in cessation of turning from 8 to
      14 d of incubation (range 88.9 to 89.2%). However, turning 96 times daily
      produced significantly better fertile hatchability that was largely due to a
      significant interaction of flock age and turning frequency; the beneficial effect
      of increased turning frequency, largely reduced late-embryonic mortality, was
      more evident in the eggs from the older flocks.

PMID- 16903486
TI  - Statins for primary prevention in type 2 diabetes.
AB  - At least 1 in 40 people in the UK have type 2 diabetes mellitus, and the
      prevalence is increasing. Such people are more likely than others to develop, and
      to die from, cardiovascular disease. Statin therapy helps to prevent
      cardiovascular disease events among patients at increased risk, with or without
      diabetes, and is standard treatment for patients needing secondary prevention.
      Here we discuss whether statins should be used routinely for primary prevention
      of cardiovascular disease in patients with type 2 diabetes irrespective of other
      risk factors.

PMID- 16903485
TI  - Effects of S6-strain Mycoplasma gallisepticum inoculation at ten, twenty-two, or
      forty-five weeks of age on the egg yolk composition of commercial egg-laying
      hens.
AB  - Commercial laying hens maintained under controlled conditions were experimentally
      inoculated with the S6 strain of Mycoplasma gallisepticum (S6MG) at 45 wk of age.
      This resulted in depressed liver lipid concentration, and inoculations at 20 and
      45 wk affected the size of various portions of the reproductive tract. In 2
      consecutive trials of the current study, the effect of age of application of S6MG
      inoculation on the egg yolk characteristics of commercial layers similarly housed
      and maintained under controlled conditions was determined. The ages of
      inoculation compared were prior to lay at 10 wk of age, during onset of lay at 22
      wk of age, and during postpeak lay at 45 wk of age. In each trial, yolk moisture
      and total lipid content were determined at 24, 32, 43, 47, and 58 wk of age. Yolk
      cholesterol concentration and yolk fatty acid profiles at wk 47 and 58 were also
      examined. Data from wk 24, 32, and 43 (effects of S6MG inoculations at 10 and 22
      wk) and data from wk 47 and 58 (effects of S6MG inoculations at 10, 22, and 45
      wk) were analyzed separately. The data of both trials were pooled then analyzed
      together. Across wk 47 and 58, percentage yolk lipid was significantly lower in
      eggs laid by birds inoculated at 10 wk compared with those inoculated at 45 wk.
      Sham-inoculated control and 22-wk inoculated groups had intermediate percentage
      yolk lipids. Compared with sham-control and 10-wk S6MG inoculation groups across
      wk 47 and 58, yolk myristic, oleic, and linolenic acid concentrations were
      reduced, whereas yolk stearic and arachidonic acid levels were increased by
      either 22- or 45-wk S6MG inoculations. In comparison with all other treatment
      groups at wk 47, yolk linoleic acid concentration was reduced by S6MG inoculation
      at 45 wk. Variable postpeak alterations in yolk total lipid and fatty acid
      content occur in response to the timing of S6MG inoculation in layers housed
      under controlled conditions.

PMID- 16903487
TI  - Is minocycline overused in acne?
AB  - Patients with moderate or severe acne vulgaris, or an inadequate response to
      topical treatments, are often treated with oral antibacterials, in particular,
      tetracyclines. Minocycline is one of the most commonly prescribed tetracyclines
      in acne, the predominant use for this drug. In 2005, around 2.5 million
      prescriptions for oral tetracyclines were dispensed in England at a cost to the
      NHS of over pound 21 million, and minocycline accounted for 40% of this
      expenditure. The drug is often recommended with claims that it is more effective,
      less likely to cause bacterial resistance, and easier to take than other
      tetracyclines. Here we consider the use of minocycline for acne.

PMID- 16903488
TI  - Topiramate for migraine prophylaxis.
AB  - About 14% of adults in the UK have migraines. Drugs used in migraine prophylaxis
      include beta-blockers (e.g. propranolol), 5HT antagonists (e.g. pizotifen),
      antidepressants (e.g. amitriptyline), antiepileptics (e.g. sodium valproate) and
      NSAIDs. The antiepileptic topiramate (Topamax-Janssen-Cilag) is licensed for the
      prophylaxis of migraine headache in patients aged over 16 years. Here we discuss
      the place of topiramate in migraine prophylaxis.

PMID- 16903489
TI  - Negative automaintenance omission training is effective.
AB  - Twelve pigeons were exposed to negative automaintenance contingencies for 17-27
      sessions immediately after brief (14-16 sessions) or extended (168-237 sessions)
      exposure to positive automaintenance contingencies, or after 4-10 sessions of
      instrumental training. In all conditions, negative automaintenance contingencies
      virtually eliminated responding, reducing response rates to an average 1.3
      responses per min. This reduction in response rate was validated by a model of
      transition between early and late response rates that assumed exponential
      transition of rates from one set of contingencies to the next. The model
      faithfully reproduced cumulative records, and yielded estimates of terminal rates
      under negative automaintenance that were close to operant level.

PMID- 16903491
TI  - An analysis of reinforcement history effects.
AB  - Four pigeons were exposed to two tandem variable-interval differential
      reinforcement-of-low-rate schedules under different stimulus conditions. The
      values of the tandem schedules were adjusted so that reinforcement rates in one
      stimulus condition were higher than those in the other, even though response
      rates in the two conditions were nearly identical. Following this, a fixed
      interval schedule of either shorter or longer values than, or equal to the
      baseline schedule, was introduced in the two stimulus conditions respectively.
      Response rates during those fixed-interval schedules typically were higher in the
      presence of the stimuli previously correlated with the lower reinforcement rates
      than were those in the presence of the stimuli previously correlated with the
      higher reinforcement rates. Such effects of the reinforcement history were most
      prominent when the value of the fixed-interval schedule was shorter. The results
      are consistent with both incentive contrast and response strength
      conceptualizations of related effects. They also suggest methods for
      disentangling the effects of reinforcement rate on subsequent responding, from
      the response rate with which it is confounded in many conventional schedules of
      reinforcement.

PMID- 16903490
TI  - Contingency discriminability and peak shift in concurrent schedules.
AB  - We investigated the effects of discriminative stimuli on choice in a highly
      variable environment using a procedure in which multiple two-key concurrent VI VI
      components changed every 10 reinforcers and were signaled by differential flashes
      of red and yellow keylights. Across conditions, five pigeons were exposed to a
      number of different combinations of the following component reinforcer ratios:
      27:1, 9:1, 3:1, 1:1, 1:3, 1:9, 1:27. Overall, there was clear control by the
      component signals in that preference, early in components and particularly before
      any reinforcers had been delivered, was ordinally related to the signaled
      reinforcer ratios. In conditions in which only two components arranged unequal
      reinforcer ratios (e.g., 27:1 and 1:27) with the remaining components arranging
      1:1 reinforcer ratios, preference before the first reinforcer in a component
      showed peak shift in that the most extreme preference did not occur in the
      unequal reinforcer-ratio components, but in 1:1 components further towards the
      ends of the stimulus dimension. The contingency-discriminability model (Davison &
      Nevin, 1999) was fitted to the data and provided an excellent description of the
      interactions between stimulus and reinforcer effects in a highly variable
      environment.

PMID- 16903492
TI  - Fix and sample with rats in the dynamics of choice.
AB  - The generality of the molar view of behavior was extended to the study of choice
      with rats, showing the usefulness of studying order at various levels of
      extendedness. Rats' presses on two levers produced food according to concurrent
      variable-interval variable-interval schedules. Seven different reinforcer ratios
      were arranged within each session, without cues identifying them, and separated
      by blackouts. To alternate between levers, rats pressed on a third changeover
      lever. Choice changed rapidly with changes in component reinforcer ratio, and
      more presses occurred on the lever with the higher reinforcer rate. With
      continuing reinforcers, choice shifted progressively in the direction of the
      reinforced lever, but shifted more slowly with each new reinforcer. Sensitivity
      to reinforcer ratio, as estimated by the generalized matching law, reached an
      average of 0.9 and exceeded that documented in previous studies with pigeons.
      Visits to the more-reinforced lever preceded by a reinforcer from that lever
      increased in duration, while all visits to the less-reinforced lever decreased in
      duration. Thus, the rats' performances moved faster toward fix and sample than
      did pigeons' performances in previous studies. Analysis of the effects of
      sequences of reinforcer sources indicated that sequences of five to seven
      reinforcers might have sufficed for studying local effects of reinforcers with
      rats. This study supports the idea that reinforcer sequences control choice
      between reinforcers, pulses in preference, and visits following reinforcers.

PMID- 16903493
TI  - The emergence of symmetry in a conditional discrimination task using different
      responses as propioceptive samples in pigeons.
AB  - In Experiment 1, 10 pigeons were exposed to a successive symbolic matching-to
      sample procedure in which the sample was generated by the pigeons' own behavior.
      Each trial began with both response keys illuminated white, one being the
      "correct" key and the other the "incorrect" key. The pigeons had no way of
      discriminating which key was correct and which incorrect, since these roles were
      assigned on a random basis with the same probability of 0.5 for each key. A fixed
      ratio of five responses was required on the correct key. However, each time the
      pigeon pecked the incorrect key, the correct key response counter reset. Five
      consecutive pecks on the correct key was the only way to end this component, and
      switch off both key lights. Two seconds later, these same keys were illuminated
      again, one green and the other red (comparison stimuli). Now, if the correct
      white key had been on the left, a peck at one color produced food, and if the
      correct white key had been on the right, a peck at the other color produced food.
      When the pigeons had learned this discrimination, they were exposed to several
      symmetry tests (simultaneous presentations of both keys illuminated the same
      color-i.e., both red or both green), in order to interchange the sample with the
      comparison stimuli. In Experiment 2, the importance of requiring discrimination
      between the samples and between the comparisons was analyzed. In Experiment 3, we
      compared the results of Experiment 1 with a slightly different experiment, which
      resulted in discrimination of key position, an exteroceptive stimulus. The
      results showed that symmetry emerged only when different responses were used as
      samples.

PMID- 16903494
TI  - Some tests of response membership in acquired equivalence classes.
AB  - Pigeons were trained on many-to-one matching in which pairs of samples, each
      consisting of a visual stimulus and a distinctive pattern of center-key
      responding, occasioned the same reinforced comparison choice. Acquired
      equivalence between the visual and response samples then was evaluated by
      reinforcing new comparison choices to one set of samples, and examining
      generalization of these choices to the other samples. Three separate experiments
      found no evidence of such generalization, as indexed by performance on class
      consistent versus class-inconsistent tests. Other tests showed that the pigeons'
      center-key response patterns during training had indeed served as a conditional
      cue for choice. These results do not support the hypothesis that different
      defined responses can become members of acquired equivalence classes.

PMID- 16903495
TI  - Measuring resistance to change at the within-session level.
AB  - Resistance to change is often studied by measuring response rate in various
      components of a multiple schedule. Response rate in each component is normalized
      (that is, divided by its baseline level) and then log-transformed. Differential
      resistance to change is demonstrated if the normalized, log-transformed response
      rate in one component decreases more slowly than in another component. A problem
      with normalization, however, is that it can produce artifactual results if the
      relation between baseline level and disruption is not multiplicative. One way to
      address this issue is to fit specific models of disruption to untransformed
      response rates and evaluate whether or not a multiplicative model accounts for
      the data. Here we present such a test of resistance to change, using within
      session response patterns in rats as a data base for fitting models of
      disruption. By analyzing response rate at a within-session level, we were able to
      confirm a central prediction of the resistance-to-change framework while
      discarding normalization artifacts as a plausible explanation of our results.

PMID- 16903496
TI  - Herbert Spencer's contributions to behavior analysis: a retrospective review of
      principles of psychology.
AB  - Herbert Spencer's Principles of Psychology (1855, first edition) was regarded by
      his contemporaries, including William James and John Dewey, as a major
      contribution to what was then a very new discipline. In this book he first
      expounded his ideas about both evolution of species and how behavior of the
      individual organism adapts through interaction with the environment. His
      formulation of the principle that behavior changes in adaptation to the
      environment is closely related to the version of the law of effect propounded
      some years later by Thorndike. He can thus be seen as the first proponent of
      selectionism, a key tenet of behavior analysis. He also explicitly attacked the
      then prevailing view of free will as being incompatible with the biologically
      grounded view of psychological processes that he was advocating, and thus put
      forward ideas that were precursors of B. F. Skinner's in this important area of
      debate.

PMID- 16903497
TI  - Leadership and the yellow brick road.

PMID- 16903498
TI  - Amalgam: has junk science caused dentists to pull it?

PMID- 16903499
TI  - Writing a curriculum vitae.

PMID- 16903500
TI  - Happiness and humor in the office is good business and good for you.

PMID- 16903501
TI  - Women's health. Seven missed diseases in women.

PMID- 16903502
TI  - Breast implants don't increase cancer risk.

PMID- 16903503
TI  - George Washington's long, painful dental odyssey.

PMID- 16903504
TI  - Keep your dentist in the loop about your health.

PMID- 16903505
TI  - Yeah, but...

PMID- 16903506
TI  - Cryotherapy versus laser photocoagulation for threshold retinopathy of
      prematurity: impact on early postoperative clinical recovery.
AB  - In a retrospective study in preterms treated with either cryotherapy (n= 16, 2000
      2001) or laser photocoagulation (n= 19, 2002-2005) for threshold retinopathy, a
      significant decrease in duration of postoperative ventilation, in postoperative
      administration of analgesics and in time until regain of full enteral feeding was
      documented in infants who received laser photocoagulation. We therefore conclude
      that - compared to cryotherapy - laser treatment for threshold retinopathy is
      associated with a faster clinical postoperative recovery.

PMID- 16903507
TI  - Confocal microscopy in multiple myeloma associated crystalline keratopathy: case
      report.
AB  - We report on the confocal microscopical findings of both corneas of a patient
      presenting a multiple myeloma associated crystalline keratopathy and the response
      to treatment. Blurred vision was the first sign of progression of the multiple
      myeloma. Confocal microscopy images show needle-like structures in the epithelium
      and stroma of the cornea which regressed after treatment of the multiple myeloma.

PMID- 16903508
TI  - Abnormal cupping of the optic disc: clinical screening before performing a
      neuroimaging examination.
AB  - Imaging studies in typical glaucomatous cupping are usually needless. This
      article reviews the various clinical presentations for considering imaging in
      patients presenting with cupped disc.

PMID- 16903509
TI  - Phthiriasis palpebrarum: 2 case reports.
AB  - Phthiriasis palpebrarum, caused by the phthirus pubis, is a rare cause of
      blepharoconjunctivitis, and is therefore often neglected. We present 2 patients
      who suffered itching and irritation at the right upper eyelid. Biomicroscopic
      examination showed a few lice and nits anchored to the eyelashes. Dermatologic
      examination revealed the presence of numerous lice and nits at the trunk and
      pubic area. The lice and nits were manually removed if possible, and the patients
      were asked to put vaseline on the eyelid margins. The patients were also treated
      with malathion 0.5% lotion. After control, two weeks later, no more lice nor nits
      were present in the first patient.

PMID- 16903510
TI  - [Bilateral optic neuropathy and non-Hodkin's lymphoma].
AB  - While ocular lesion is commonly known in lymphoma, optic neuropathy is very rare
      : 1,3% of lymphomas affecting the central nervous systems. OBSERVATION: Authors
      report the case of a 75 year old patient treated in the haematology department
      for 8 years, for a large cell B phenotype stage IV lymphoma for which he received
      7 chemotherapy courses (CHOP protocol). After a 4 year remission period, he
      presented a relapse with a rapid progressive bilateral impairment of visual
      acuity observed for a week before his admission. The ophthalmologic exam revealed
      no light perception and no afferent reflex on the right eye. There was light
      perception and weak afferent reflex on the left eye. The anterior segment was
      normal on both eyes and fundus examination revealed a bilateral stage I papillar
      oedema. The general exam showed a right facial palsy and an impairment of general
      condition. The orbital CT scan revealed a significant thickening of both optic
      nerves caused by lymphomatous infiltration. A chemotherapy with highly dosed IV
      and intrathecal methotrexate was performed. DISCUSSION: the optic neuropathy is
      usually associated with a generalized lymphoma with central nervous system
      involvement, but sometimes can precede the systemic spread of the disease. Apart
      from infiltration, the optic nerve can be compressed by an intracranial or
      orbital tumor. The optic neuropathy can also be caused by lymphomatous
      leptomeningitis.

PMID- 16903511
TI  - Comparative safety profile between "modern" trabeculectomy and non-penetrationg
      deep sclerectomy.
AB  - PURPOSE: To compare the incidence and the severity of short-and medium-term
      complications following "modern" trabeculectomy (mTRAB) with non-penetrating deep
      sclerectomy (NPDS). MATERIALS AND METHODS: Comparative retrospective
      nonrandomized study including 65 eyes (55 patients) (mean age: 68.6 years) with
      medically uncontrolled glaucoma. mTRAB was performed in 43 eyes, NPDS in 22 eyes.
      mTRAB was performed according to a slightly modified P.T. Khaw protocol. NPDS
      procedures were done according to Kozlov's and Mermoud's technique with SKGEL
      implant in 18/22 eyes. Intraoperative antimetabolites (AMETAB) were given in 25
      eyes (58%) in the mTRAB and 17 (77%) in the NPDS (p>0.05). RESULTS: Mean follow
      up was longer in NPDS (10.7+/-5.5 months) than in mTRAB (8.5+/-3.4 months)
      (p<0.05). Preoperatively, the two groups were comparable in respect of age, type
      of glaucoma, mean IOP, severity of VF defects and bleb failure risk factors
      (p>0.05). Peroperatively, mTRAB were uneventful in 86% vs 90% of NPDS. 1st month
      postop complications occurred in 60.4% in mTRAB and 77.2% in NPDS (P>0.05). Most
      of them were minor and transient in both surgeries. Postop early anterior chamber
      inflammation was mild to moderate in all cases. The incidence of wound leaks (21%
      in the mTRAB group and 18% in the NPDS group) and hyperfiltration related
      complications (14% and 13.6% respectively in the mTRAB and NPDS group) were
      comparable between the two procedures (p > 0.05). Intraoperative antimetabolite
      application was not associated with an increased rate of postoperative
      hyperfiltration related complications. Scarring of filtration blebs had concerned
      a lower percentage of mTRAB eyes (19%) than the NPDS (36%). The number for 5-FU
      injections was less - although not significantly - in the mTRAB than in the other
      group (18.6% in mTRAB versus 41% in NPDS (p=0.05). Late complications were not
      observed in the mTRAB group. Iris prolapse associated with increased IOP occurred
      in 3 of the 22 NPDS procedures (13.6%). Final mean visual acuity was unchanged
      compared with preop value and was similar between the 2 groups (p>0.05). Diffuse,
      mildly vascularized filtration blebs were observed in 84% in mTRAB and 64% in DS
      (p>0.05). Mean IOP significantly decreased from 24.8+/-8.3 mm Hg to 13.4+/-4,3 mm
      Hg in mTRAB and from 25.1+/-6.5 mm Hg to 14.7+/-4.6 mm Hg in DS (p> 0.05). It was
      not different between the 2 groups with and without AMETAB augmentation. 70% of
      the mTRAB achieved a final IOP < or = 15 mmHg vs 41% in NPDS (p<0.05). The mean
      number of postop medications was 0.49 in mTRAB and 0.96 in NPDS (p<0.05).
      Complete (target IOP reached without meds) and qualified (target IOP reached with
      and without meds) final success rates were 60% and 88% in mTRAB and 36.4% and
      68.2% in NPDS (p>0.05). CONCLUSIONS: Whether surgery was augmented with
      intraoperative antimetabolite or not, mTRAB revealed as a priority to be
      associated with comparable and even less complications than deep sclerectomy.
      Owing to the limitations of our study and until further confirmation, our results
      have suggested that mTRAB was associated with a slightly more important IOP
      reduction as well as higher success rates than NPDS.

PMID- 16903512
TI  - [Pseudoexfoliation syndrome in Moroccan patients with cataract scheduled for
      sugery].
AB  - PURPOSE: To evaluate the prevalence of pseudoexfoliation syndrome (PES) in
      Moroccan patients with age-related cataract scheduled for surgery. PATIENTS AND
      METHODS: In a retrospective study, 837 consecutive eyes with age-related cataract
      scheduled for surgery were evaluated for the prevalence of PES, type of cataract,
      intraocular pressure (IOP) and operative complications. RESULTS: Exfoliation
      material was detected in 82 patients (9.8 %). The mean age was 69.3 years with no
      sex predilection. The condition was unilateral in 44 cases (53.7%) and bilateral
      in 38 cases (46.3%). The prevalence of PES increased with age (p=0.02). Patients
      with hypermature cataract had significantly more PES (p <0.001). Mean IOP was
      significantly higher in eyes with PES (17.7 +/- 6.4 mmHg) than those without PES
      (14.3 +/- 2.9 mmHg) (p<0.001). Operative complications occurred more frequently
      in patients with PES: 14 (17 %) than in those without PES: 58 (6.9 %).
      DISCUSSION: PES is a generalized degenerative fibrillopathy bound to age. The
      ethiopathogeny remains even unknown. The epidemiological data concerning the
      prevalence of the SPE in the African populations are scarce, and have not been
      published in Morocco, what motivated this study. Our study shows that this
      syndrome is common in Moroccan patients scheduled for cataract surgery with a
      prevalence of 9.8%. Its presence constitutes an important risk factor of primary
      open-angle glaucoma, and exposes more to peroperative complications at the time
      of surgery of cataract, independently of the technique used. CONCLUSION: There is
      great variation in the prevalence of PES among people of different regions and
      ethnic groups, although many factors interfere in the comparative analysis of
      results, hence the interest to achieve other complementary epidemiological
      studies.

PMID- 16903513
TI  - Visual outcome in children with juvenile idiopathic arthritis related uveitis.
AB  - PURPOSE: To determine the incidence and characteristics of uveitis in a cohort of
      patients with juvenile idiopathic arthritis (JIA) as well as the nature of
      treatment and the risk factors for visual loss. PATIENTS AND METHODS:
      Retrospective review of 52 patients with JIA, screened for uveitis between 1995
      and 2005. The first group, presenting with symptoms of arthritis and uveitis, was
      diagnosed at screening. The second group presented with symptoms of uveitis,
      without any rheumatological complaints at the time of diagnosis. During follow
      up, reactivation of uveitis and complications were registered and treated when
      indicated. RESULTS: Seventeen patients had symptoms of uveitis at time of
      presentation or developed uveitis at follow-up. Ten of this patient group had
      oligo-arthritis, 16 were antinuclear antibody (ANA) positive, 16 were girls.
      Three patients presented with ophthalmological symptoms without rheumatological
      complaints. In this group, complications were more pronounced. Treatment in all
      patients consisted of topical corticosteroids and dilating drops at different
      intervals. Visual acuity was good in most patients. CONCLUSION: In this
      retrospective study, the risk of uveitis was higher in ANA- positive girls with
      oligoarthritis. To reduce severe disease at presentation, earlier diagnosis of
      JIA, earlier referral for slit lamp examination and universal screening of vision
      in childhood are necessary.

PMID- 16903514
TI  - Orbital osteoma: three case reports.
AB  - INTRODUCTION: Osteoma is the most frequent benign tumor of paranasal sinuses. It
      is generally asymptomatic and usually discovered by chance during radiological
      imaging. Three cases with orbital extension are reported and discussed.
      OBSERVATIONS: 1st observation: Mrs. M.N. is an 18 years-old caucasian female who
      presented a stony orbital deformity associated with chronical dacryocystitis.
      Tomography of the orbit revealed a probable ethmoidal osteoma compressing the
      lacrimal canals. The management consisted in a surgical excision of the whole
      tumor by external approach, associated with a dacryocystorhinostomy. The
      patient's follow-up for the last 12 months was normal. 2nd observation: Miss K.A.
      is a 16 years-old caucasian female who came to consultation for a swelling of the
      medial angle of the left eye. Computed tomography images showed a fronto
      ethmoidal process displaying a bone density consistent with an osteoma. The tumor
      was removed through an external ethmoidectomy. The patient was free of symptoms
      at 6 months follow-up. 3rd observation: Mrs. F. Z. is a 45 years-old patient who
      presented a 5 years history of right painful exophthalmos. The computed
      tomography was consistent with a fronto-ethmoidal osteoma with intraorbital
      extension near the optic nerve. The surgical excision was limited to the
      intraorbital portion. Postoperative complications included ptosis and diplopia.
      DISCUSSION: Osteomas most commonly affect the fronto-ethmoid sinuses. They rarely
      show intraorbital extension or cause intracranial complications. They are
      generally asymptomatic. Symptoms are generally of late onset and are a
      consequence of tumoral growth and compression of neighbouring organs, as it is
      the case in our patients. Tumoral exophtalmos is the major ophthalmological sign.
      The computed tomography is of a great contribution, not only for diagnosis but
      also for the choice of the surgical approach. The classical surgical technique
      consists generally in a surgical excision of the osteoma. This surgery may induce
      ocular or neurochirurgical complications. CONCLUSION: Osteomas of the paranasal
      sinuses are usually asymptomatic. If they become voluminous, they may cause
      orbital manifestations and serious complications. The rarity of ethmoidal osteoma
      with orbital growth made our cases interesting to report.

PMID- 16903515
TI  - [Treatment of chalazion with incision and curettage in African patients of the
      negroid race].
AB  - OBJECTIVE: To evaluate the efficacy of incision and curettage in the treatment of
      chalazion in black African patients. METHODS: In a prospective study performed
      between February 1999 and February 2000, 25 black African patients with chalazion
      (27 eyes, 30 chalazions), ranging in age from 15 to 51 years (mean age +/-SD,
      25.2 years +/-7), were treated with incision and curettage. Measurements of
      eyebrow height, pretarsal skin height, crease height, inferior eyelid height and
      the palpebral fissure height were performed before and after treatment. Success
      was defined as a total disappearance or a decrease in size (less than one
      millimeter). RESULTS: Success was achieved in all of 25 patients. Recurrence
      occurred in 3.0% after 5 to 6 weeks. During a mean +/-SD of 4.7 months +/-2.9 of
      follow-up, fistula (3.0%) was noted as postincision ocular complication. After
      treatment, a significant decrease of pretarsal skin (P = 0.018) and inferior
      eyelid height (P=0.004) measurements and an increase in palpebral fissure height
      measurement (P = 0.025) were noted. CONCLUSION: Incision and curettage in
      chalazion treatment appears to be effective in managing chalazion in black
      African patients as reported in previous studies in Caucasian patients.

PMID- 16903516
TI  - [Idiopathic pulmonary fibrosis].
AB  - Idiopathic pulmonary fibrosis is a fibroproliferative disorder characterized
      histopathologically by heterogenous interstitial fibrosis with fibroblastic foci
      and honeycomb lung. The diagnosis is based on a pluridisciplinary approach,
      integrating the clinical evaluation, the chest high-resolution computerized
      tomography features, and the pathological pattern of usual interstitial pneumonia
      on video-thoracoscopic lung biopsy when performed. When the tomodensitometric
      pattern is typical (50% of the cases), the diagnosis may be made without a lung
      biopsy. No treatment has proven benefit in survival. Treatment with N
      acetylcysteine in association with corticosteroids and azathioprine has recently
      shown a modest functional improvement. Clinical trials are strongly needed in
      this still uncurable disease with median survival at 3 years of only about 50%.

PMID- 16903518
TI  - [Ophthalmology. Ensuring that everyone has the best possible vision].

PMID- 16903517
TI  - [Angioedema and angiotensin-converting enzyme inhibitors].

PMID- 16903519
TI  - [Refractive surgery: a solution for elimination of glasses?].
AB  - Refractive surgery corresponds to all surgical methods designed for correction of
      refractive errors called ametropia (myopia, hyperopia, astigmatism and
      presbyopia). This area in ophthalmology, recently opened, is in continuous
      progress concerning techniques of treatment and also of diagnosis. These
      innovations allowed spectacular performances making possible the corrections of
      all refractive defaults. Two main categories can be distinguished depending on
      the corneal or intraocular location of the surgery. The first group includes
      incisions, excimer photoablation, laser thermokeratoplasty and intrastromal
      segments. The second group represents implantation of intraocular lens in front
      of natural lens (phakic IOL) or taking the place of the lens after its removal
      (pseudophakic IOLs).

PMID- 16903520
TI  - [Age-related macular degeneration].
AB  - Age-related macular degeneration (AMD) is the commonest overall cause of
      irreversible blindness in patients aged 50 or over in the western world. It is a
      spectrum of related diseases that have in common the progressive decline of
      vision as a consequence of dysfunction of the central retina and its underlying
      supporting elements, principally the retinal pigment epithelium and choroid in
      older adults. The disease has been traditionally classified into early and late
      stages with its dry and wet forms. Patients with age-related maculopathy should
      consider taking a dietary supplement such as that used in AREDS. There is no
      effective treatment for geographic atrophy. The exudative AMD is approached
      depending on the type and localisation of choroidal new vessels. Laser
      photocoagulation has only been shown to be beneficial for extra and juxtafoveal
      well defined lesions. PDT with verteporfin is effective in the management of
      patients with subfoveal predominantly classic lesions. A variety of molecules
      such as bevacizumab, pegaptanib sodium and ranibizumab, specifically targeted to
      different pathologic pathways in AMD, have been identified to their therapeutic
      potential. Research is actively being pursued in preclinical models both in
      academic laboratories and in the pharmaceutical industry, including multiple
      early stage clinical trials. There is no strong evidence to support benefits of
      submacular surgery in the management of neovascular AMD.

PMID- 16903522
TI  - [Uveitis].
AB  - Uveitis are a group of heterogeneous entities, with very diverse causes, sharing
      intraocular inflammation as a common denominator. Uveitis are uni- or bilateral
      and the localization of inflammation defines anterior, intermediate or posterior
      uveitis. The course of the disease can be chronic or acute. Uveitis are isolated
      or belong to manifestations of a systemic disease. The identification of a cause
      of uveitis is based on the analysis of ophthalmic signs and on searching for
      extraocular manifestations. Laboratory tests should be prescribed according to
      clinically defined hypotheses. Causes are infectious (bacterial, parasitic,
      mycotic or viral) or only inflammatory. The prognosis of uveitis is mostly based
      on their consequences to the macula. When the cause of uveitis is determined,
      therapeutic guidelines may be applied.

PMID- 16903521
TI  - [The effects of medications on the eyes].
AB  - The visual system is very sensitive to side effects of medicines, either
      regarding systematic complications of eye drops or ocular complications following
      oral or intravenous treatments. For the latter, ophthalmologic regular monitoring
      is mostly the best preventive measure since most of iatrogenic abnormalities are
      reversible after ruling out the treatment. However, some ocular complications are
      poorly reversible, as for example with antimalarial drugs or vigabatrin.
      Concerning systemic complications of ocular treatments, their risk is often
      underestimated, while the passage of drugs in the blood can sometimes reach
      similar rates than those observed after an oral administration, as it is the case
      with some beta-blockers ophthalmic solutions. It is also advisable to distrust
      overdoses, or accidental oral ingestions, of parasympatholytic mydriatics which
      can induce neurological and cardiac complications in children or in elderly.

PMID- 16903523
TI  - [Pathology of the ocular surface].
AB  - The ocular surface is a new concept including the cornea, the conjunctiva, the
      lids and the lachrymal tear film in a new approach as an anatomic, physiologic
      and physiopathologic entity. The goal of the ocular surface, in a functional
      approach, is the maintenance of the corneal transparency. Ocular surface diseases
      are very frequent with numerous aspects and aetiologies and with no specificity
      for functional or clinical signs, particularly in chronical forms. Inflammation
      is most frequently associated in chronical diseases, subclinically as in
      keratoconjunctivitis sicca or, predominantly in allergy or immunologic
      dysfunction. Ocular surface is also involved in several kinds of subspecialties
      as iatrogenic toxicity, contactologia, and, on a surgical way, corneal refractive
      surgery, ocular surface reconstruction with graft and also filtering surgery for
      glaucoma.

PMID- 16903524
TI  - [Visual acuity and work and leisure abilities].
AB  - The visual medical ability is necessary for a large number of jobs, sports and
      for vehicles driving. A high heterogeneousity exists in the required standards,
      the measurement techniques and the people who realize these visual abilities.
      This heterogeneousity is too rarely correlated to an accidentology which is
      increased by a lack of scientific study. A review non exhaustive of jobs and
      occupations is here presented.

PMID- 16903525
TI  - [Visual acuity and driving].

PMID- 16903526
TI  - [Shared medical decision making].

PMID- 16903527
TI  - [Pertussis].

PMID- 16903528
TI  - [Principal complications of pregnancy: the threat of premature labor].

PMID- 16903529
TI  - [Doctor-patient relationship: disclosure of serious illness, education of
      patients suffering from chronic illness, personifying medical care].

PMID- 16903530
TI  - [Genital hemorrhage].

PMID- 16903531
TI  - Accessing root canal systems: requirements and techniques.

PMID- 16903532
TI  - Permanent diagnostic provisional restorations for predictable results when
      redesigning the smile.
AB  - In order to determine the optimal method of patient care, the patient's existing
      clinical condition must be accurately diagnosed and treatment objectives (eg,
      biocompatibility, aesthetics, long-term function) established accordingly. Once
      analysis of the condition is complete, the correct restorative procedure can be
      selected and the complications presented by the patient can be addressed.
      Comprehensive radiographic and clinical examinations are integral in determining
      the preoperative status of the patient and, consequently, in evaluating the
      possibility of actually achieving a successful rehabilitation.

PMID- 16903533
TI  - Digital radiography: improving image quality.

PMID- 16903534
TI  - Guided implant surgery and the use of osteotomes for rehabilitation of the
      maxilla.

PMID- 16903535
TI  - Immediate provisionalization of a single-tooth implant with a temporary cylinder
      in one surgical appointment.

PMID- 16903536
TI  - Prosthetic considerations for implant surgery.

PMID- 16903537
TI  - Intraoral onlay bone grafts for implant site preparation.

PMID- 16903538
TI  - Surgical armamentarium in implant dentistry.

PMID- 16903539
TI  - Presenting implant therapy for cost-conscious patients.

PMID- 16903540
TI  - Bisphosphonates and their impact on patient treatment.

PMID- 16903541
TI  - Treating the atrophic posterior maxilla by combining short implants with
      minimally invasive osteotome procedures.
AB  - Edentulous sites in the posterior maxilla are often compromised by reduced bone
      volume, prohibiting the placement of 10-mm implants without sinus augmentation.
      The use of shorter implants minimizes the need for more extensive sinus floor
      elevation, thus reducing treatment duration and morbidity. Two implant designs
      are presented in combination with localized internal sinus floor elevation to
      restore the posterior maxilla. This simplified treatment modality can make
      implant rehabilitation of the atrophic posterior maxilla more accessible and more
      palatable to even the most reluctant patients and referring doctors.

PMID- 16903542
TI  - Envisioning the definitive restoration using the core buildup.

PMID- 16903543
TI  - Cosmetic recontouring of gingival tissues and alveolar bone.

PMID- 16903544
TI  - The evolution of the porcelain laminate veneer.

PMID- 16903546
TI  - [The tyranny of p].

PMID- 16903545
TI  - Achieving form and function for Class II restorations using aesthetic resin
      stratification.
AB  - It can be challenging to reproduce the appropriate three-dimensional contours
      when the proximal walls of posterior teeth have been lost. This presentation will
      demonstrate the fundamentals required to achieve predictable success when placing
      direct posterior composites in these Class II sites. The keys to successful
      placement of resin materials (eg, adhesive technique, integration of form and
      function, color match) are covered herein. When placing a direct resin
      restoration, clinicians must have a sound understanding of tooth morphology,
      combined with the proper techniques, outlined in the clinical case, in order to
      obtain an acceptable aesthetic restoration.

PMID- 16903547
TI  - [Leydig cell tumor: our experience. Bibliographic review].
AB  - OBJECTIVES: To report the case-series of Leydig cell tumors diagnosed at our
      center, and to perform a bibliographic review on the topic. METHODS:
      Retrospective review of the clinical records of all patients with the diagnosis
      of Leydig cell tumor in our center over the last 12 years. We evaluated the
      clinical, diagnostic and therapeutic features, as well as outcomes. RESULTS: Four
      patients were diagnosed and treated in our department over this period. Mean
      patient age of the time of diagnosis was 51 years. Each of our cases have a
      different presentation. The two patients who underwent sperm analysis had
      azoospermia. None of the cases showed anomalous hormonal studies. Seventy-five
      percent of the cases showed ultrasound signs compatible with testicular
      neoplasia. In all of them surgical treatment was undertaken (inguinal
      orchyectomy); one of the patients underwent chemotherapy due to metastasis,
      having a good response. Mean follow-up is 76 months. CONCLUSIONS: It is a rare
      testicular tumor. Inguinal orchyectomy is the treatment of choice. Its good
      outcome is remarkable.

PMID- 16903548
TI  - [Radical prostatectomy in patients with history of transurethral resection of the
      prostate].
AB  - OBJECTIVES: To perform a retrospective evaluation of surgical complications and
      morbidity in patients undergoing radical retropubic prostatectomy (RRP) as
      elective treatment for organ-confined prostate cancer in our center with previous
      transurethral resection of the prostate (TURP). METHODS: Between 1980-2004 we
      performed 59 radical prostatectomies in patients with previous TURP. We analyze
      the morbidity and mortality of the RRP, its functional outcomes, and the
      accordance between clinical and pathological stage. RESULTS: Mean time between
      TURP and RRP was 16 months. Mean patient age at the time of diagnosis was 63
      years. Clinical stage: 16 T1a, 18T1b, 20T1c, 3T2a, 2T2b. Average surgical time
      was 180 minutes. Intraoperative events: technical difficulties in the dissection
      of the gland 57%, bladder neck preservation 27%, neuro vascular bundles
      preservation 3.39%, ureter ligation 1.69%, rectal laceration 1.69, urethrorrhagia
      1.69%, urinary leak 5%, and blood transfusions 11.8%. Postoperative
      complications: urinary tract infection 10.17%, wound infection 10.17%, pelvic
      hematoma 5.08%, deep vein thrombosis 1.69%, and one sudden death of unknown cause
      one month after surgery. Pathologic report: 49pT2b, 8 pT3 and 2pT4. Late
      complications: erectile dysfunction 85.7%, vesicourethral anastomosis stenosis
      10.3%, and complete urinary incontinence 3%. CONCLUSIONS: Radical retropubic
      prostatectomy in patients with previous TURP is technically more difficult and
      has comparable outcomes to RRP patients without previous TURP.

PMID- 16903549
TI  - [Neurourological characterization of myelomeningocele in the adult patient].
AB  - OBJECTIVES: To characterize the neurourological features of the vesicourethral
      dysfunction of patients with cogenital myelomeningocele when they reach the adult
      age. METHODS: We report the results of the neurourological physical examination
      and video urodynamic tests of 52 adult patients born with myelomeningocele, with
      ages ranging from 18 to 14 years (mean age 20.7) controlled over the last 14
      years in the Urodynamics Unit of the Hospital Gregorio Moranon in Madrid. The
      neurological level of the lesion was evaluated in all of them. Following these
      results we established the diagnosis of the lesion of the three constitutive
      elements of the vesicourethral innervation (sympathetic, parasympathetic, and
      pudendal) in order to classify the lower urinary tract neurogenic dysfunction of
      the patients based on lesion level and type of damaged innervation. RESULTS: The
      alteration of the perineal sensitivity and diminishment of the anal sphincter
      tone, in addition to absence of anal voluntary controlled and bulbocavernosus
      reflex, where the most frequent findings in the neurourological physical
      examination. Detrusor behaviour was predominantly areflexic (88.4%), in
      association with diminished bladder compliance in half of the cases. The
      sphincter was not competent during the filling phase in 51.9% of the cases,
      competent in 42.3%, and normal in the remainder 5.7%. During the voiding phase we
      confirmed the absence of sphincter relaxation in 82.6% of the cases. There was a
      predominance of the lower level of lesion in all three sympathetic,
      parasympathetic and pudendal nerves. In almost all patients (96.7%) there was
      lesion in at least two of the three types of innervation. The most frequent
      neurogenic dysfunction of the lower urinary tract was the multiple inferior motor
      neuron pure lesion (65.3%), also finding pure superior motor neuron (3.8%), mixed
      multiple (9.6%), and pure single lesions (1.9%). Three patients presented a
      normal vesicourethral function. CONCLUSIONS: We demonstrated the multiplicity of
      lower urinary tract neurogenic dysfunction in adult patients with congenital
      myelomeningocele, its occasional absence, the lack of correlation with the
      neurological level of the lesion, and the predominance of the multiple inferior
      motor neuron pure type of lesion.

PMID- 16903550
TI  - [The rupture of the renal graft].
AB  - OBJECTIVES: The renal graft rupture (RGR) was first described in 1968; it is a
      severe situation, generally appearing in the immediate post-operative period.
      OBJECTIVES: To retrospectively analyze the incidence of renal graft rupture in
      the population of patients who underwent kidney transplant in the Renal
      Transplant Department of the Angerich Hospital. METHODS: 492 kidney transplants
      were performed from 1-1-1992 to 7-31-2005. 422 (85.7%) cadaver donor transplants
      and 70 (14.3%) live related donor transplants. RESULTS: 11 renal ruptures were
      observed, with a clinical picture characterized by sudden pain in the graft area,
      hypotension, and hematocrit descent. CT scan confirmed the diagnosis. Seven
      patients underwent transplant nephrectomy (one of them 24 hours after surgical
      repair), another two were surgically repaired successfully, and for the other two
      patients a conservative management with watchful waiting also resulted in graft
      preservation. All cases where cadaver donor drafts. CONCLUSIONS: 1) The renal
      graft rupture is a rare (2.8% in our series) severe complication characterized by
      hemodynamic instability, with no diagnostic doubts about its presentation in most
      cases. We use ultrasound as the diagnostic test. 2) In our series we were able to
      preserve 40% of the kidneys with low morbidity. 3) This complication appeared in
      cadaver donor kidneys in all cases (11/386; 2.8%).

PMID- 16903551
TI  - [Endoscopic treatment of the vesicoureteral reflux in children: preliminary
      experience with the subureteral injection of Coaptite].
AB  - OBJECTIVE: To review our experience in the endoscopic treatment of vesicoureteral
      reflux (VUR) in children with the subureteral injection of calcium hydroxyapatite
      (Coaptite). METHODS: The serie includes thirteen children whose age ranged
      between 6 and 13 years. The Coaptite implant was injected subureterally to 20
      ureteral units (UU) affected by VUR grades I-IV. VUR was unilateral in six
      patients (46%), bilateral in seven (54%). There were 7 primary cases and 6
      secondary to bladder dysfunction and duplex systems. RESULTS: Mean follow-up was
      19 months (6-28 months). VUR was cured in 75% of cases after a single injection.
      A second injection resolved 2 out of 4 treated UU (50%) rendering a global
      success rate of 85%. This cure rate was achieved for 13 and 7 procedures treating
      primary and secondary VUR, respectively. 77% of patients reported no adverse
      events with only 23% of them complaining of transient mild lumbar and hypogastric
      discomfort limited to the first postoperative day. In 2 children postoperative
      urinary infection was detected. CONCLUSIONS: Endoscopic subureteral injection
      with Coaptite is a simple technique well tolerated in children. In 85% of primary
      and secondary cases cure was achieved with minimal morbidity.

PMID- 16903552
TI  - [Evaluation of the calcium ionophore induced acrosome reaction: a more realistic
      approach to the fecundant capacity of the spermatozoid].
AB  - OBJECTIVES: The aim of this investigation was to evaluate the acrosome reaction
      by fluorescence microscopy and the flow citometry in a group of men with unknown
      fertility. METHODS: Each individual gave a semen sample for the analysis of the
      calcium ionophore-induced acrosome reaction after the capacitation process, using
      lectin Pisum sativum aglutinina (fluorescence microscopy) and antibody anti-CD46
      (flow citometry). RESULTS: Five of out six individuals increased the number of
      the sperm with calcium ionophore-induced acrosome reaction versus the percentage
      of spontaneous acrosome reaction, using fluorescence microscopy (7.4 +/- 2.4 vs
      22.5 +/- 10.1) and flow citometry (8.5 +/- 2.8 vs 25.4 +/- 6.0). On the other
      hand, the other individual the values of the acrosomal reaction with calcium
      ionophore A23187 were similar to those of the spontaneous reaction. CONCLUSIONS:
      Both techniques are useful to evaluate the in vitro capacity of the spermatozoa
      to undergo acrosomal reaction, after the capacitation, without fusion between the
      sperm and the egg, but the flow citometry is more objective and allow the
      detection of a higher cell numbers of cells. On the other hand, although the
      individual that did not respond to the stimulus with calcium ionophore has
      unknown fertility, the obtained results allow to propose that the evaluation of
      the acrosomal reaction could be a useful tool in the study of the men who consult
      for infertility.

PMID- 16903553
TI  - [Our experience with the Nesbit technique for the treatment of Peyronie's
      disease].
AB  - OBJECTIVES: The Nesbit technique is the reference technique for the surgical
      correction of the penile incurvation of Peyronie's disease. We report our
      experience at the Centro Urologico San Ignacio. METHODS: 68 patients with stable
      penile incurvation who requested surgical correction. Correction of the curvature
      is defined as > or = 80% rectification of the pathologic angle. Mean patient age
      was 44 years (31-77). 53% of the patients presented difficulties for penetration,
      20% partner's discomfort on intercourse, and 27% requested surgery for aesthetic
      reasons. Penile deviation was dorsal in 42% of the patients, to the left in 46%
      and to the right in 12%. The curvature angle was less than 30 degrees in 28%,
      between 30 degrees-45 degrees in 36%, between 45 degrees-60 degrees in 37% and >
      60 degrees in 7%. RESULTS: Mean follow-up of the series was 36 months. 20% of the
      patients had a penile shortening longer than 1.5 cm. 85% of the patients are
      satisfied with the results. The most frequent complaint was penile shortening.
      Correction was achieved in 92% of the patients. Four patients were reoperated:
      two of them for significant phimosis three months after surgery, and the other
      two for curvature recurrence. CONCLUSIONS: The Nesbit technique is a simple
      technique, with a low complication rate, and good results both in curvature
      correction and patient satisfaction.

PMID- 16903554
TI  - [Post chemotherapy laparoscopic retroperitoneal lymph node dissection].
AB  - OBJECTIVES: To describe the laparoscopic excision of a postchemotherapy
      retroperitoneal residual mass in a patient with mixed germ cell testicular tumor.
      METHODS/RESULTS: We report the operative technique of laparoscopic excision of a
      retroperitoneal mass in a 33 year old patient with mixed germ cell testicular
      tumor. The patient is placed in a lateral decubitus right lumbotomy position and
      trocars are introduced into the abdominal cavity. Once the retroperitoneum is
      approached, and after a Kocher manoeuvre of the duodenum, the interaortocaval
      mass is identified and excised. The operation is completed with lympadenectomy
      down to the common iliac artery bifurcation bilaterally. CONCLUSION: The
      laparoscopic approach is another option for the surgical treatment of residual
      masses after chemotherapy in testicular tumors. Nevertheless, previous
      laparoscopic experience is necessary due to its difficulty.

PMID- 16903555
TI  - [The treatment of metastasic testicular pure mature teratoma].
AB  - OBJECTIVE: Given the low frequency of testicular teratoma in relation to the rest
      of germ cell testicular tumors and the various treatment options for advanced
      stages, we report one case of advanced testicular mature teratoma with
      retroperitoneal adenopathy in which orchyectomy was performed after
      retroperitoneal lymphadenectomy, with the some pathology found in the primary
      tumor. METHODS: We do an update on the treatment for these stages with the
      possibility of beginning with chemotherapy leaving lymphadenectomy for residual
      masses, or the contrary, being most cases treated in a mixed way. CONCLUSIONS:
      Without clear evidence for guidelines in these tumors, it is recommended to
      individualize the treatment for each patient, accordingly to tumor
      characteristics, probability of relapse and follow-up.

PMID- 16903556
TI  - [Renal metastases of a squamous cell carcinoma of the lung. Case report and
      bibliographic review].
AB  - OBJECTIVE: We report a new case of renal metastasis of a lung carcinoma. METHODS:
      59-year-old male presenting to the outpatient clinic with a clinical picture
      compatible with renal colic and hematuria. RESULTS: Ultrasound showed a solid
      cystic tumor in the lower pole of the kidney without hydronephrosis. Abdominal
      pelvic CT scan reported retroperitoneal adenopathies > 1 cm in the area of the
      aorta-cava and a 5 cm heterogeneous mass. CONCLUSIONS: Renal metastatic lesions
      of patients with lung cancer present more frequently due to the higher accuracy
      of radiological tests and have, as well as the primary tumors, very poor survival
      rates.

PMID- 16903558
TI  - [Chronic pelvic pain as a complication of cystourethropexy with tension free
      vaginal tape. Case report].
AB  - OBJECTIVE: To report an interesting case of a rare complication of
      cystourethropexy, as well as its precise diagnosis and results after treatment.
      METHODS: We reviewed the medical records of the patients as well as their
      operative report and she underwent outpatient follow-up for the following six
      months. We descriptively report the findings. RESULTS: It is the case of a female
      patient presenting a foreign body rejection of a suburethral tension free vaginal
      tape (TVT). She complained of severe pain in the immediate postoperative period,
      which led to retrieval of the tape in spite of a good continence result.
      CONCLUSIONS: Foreign body rejection is a rare complication of vaginal tapes; it
      is rarely taken into account but it should be present in any exclusion diagnosis
      because the possibility of tape retrieval is not always associated with
      recurrence of the incontinence.

PMID- 16903557
TI  - [Metastasis of a renal cell carcinoma in the corpora cavernosum of the penis.
      Case report and bibliographic review].
AB  - OBJECTIVE: We describe a rare case, the metastasis of a renal clear cell
      carcinoma in the corpora cavernosum of the penis. METHODS: 53-year-old patient
      presenting with a painful, hard tumor in the penis three months after right
      radical nephrectomy with cavotomy and thrombus excision. RESULTS/CONCLUSIONS:
      Imaging tests and biopsy led to the diagnosis of metastasis of a renal carcinoma
      in the corpus cavernosum, which was confirmed on the pathologic study of the
      specimen after penectomy. The appearance of renal carcinoma metastases in the
      penis is generally associated with advanced tumor stage, therefore associated
      with bad prognosis as in the reported case.

PMID- 16903559
TI  - [VURD syndrome with contralateral renal dysplasia in the adult].
AB  - OBJECTIVE: To report one case of VURD syndrome (posterior urethral valves,
      vesicoureteral reflux, and renal dysplasia) in an adult. METHODS: 32-year-old
      male patient with recurrent urinary tract infections and the diagnosis of VURD
      syndrome after imaging tests ond cystoscopy. RESULTS: One year after valve
      resection the patient keeps renal function and adequate voiding without needing
      dialysis. CONCLUSIONS: The VURD syndrome is a congenital disease, frequently with
      poor prognosis in the first years of life. Etiology is not clear. A cause-effect
      relationship between dysplasia and obstruction-reflux has been proposed;
      alternotively, the "theory of the bud" suggests vesicoureteral reflux and renal
      dysplasia are the result of an anomaly of the ureteral bud and not necessarily of
      obstruction and/or VURD per se.

PMID- 16903560
TI  - [Well-differentiated lymphocytic lymphoma of the prostate. Case report and
      bibliographic review].
AB  - OBJECTIVE: To report a case of prostate lymphoma and a brief review of the
      literature. METHODS/RESULTS: A 70 year-old mele patient was referred to the
      Urology departament with a clinical picture of prostatism, with acute urinary
      retention (AUR). Surgery with retropubic prostatectomy was performed, and
      pathology revealed a primary prostate lymphoma. The patient was referred to the
      departament of Oncology where he received polychemotherapy and radiotherapy. The
      patient is currently followed by regular visits to Urology outpatients service.
      The case study is followed by a brief bibliographic review, where we analyse
      clinical menifestations of this entity, complementary studies useful for
      diagnosis (laboratory test, trasrectal prostate biopsy, transuretral resection,
      ultrasound and computerised axial tomography), treatment options (surgery,
      polychemotherapy, radiotherapy) as well as survival in these patients.
      CONCLUSIONS: Of the cases reviewed, mean age at diagnosis was 57 years. Clinical
      debut was with prostate symptoms, with or without AUR and sometimes
      manifestations of renal failure due to obstructive uropathy, as well as general
      symptoms (astenia, anorexia, weight loss). PSA values remain unaltered in
      prostate lymphoma patients. Histologic diagnosis may be made by transrectal
      prostate biopsy, although transurethral resection (TUR) may be necessary for
      confirmation. Ultrasound and CT scan are of great utility for diagnosis of both
      local and distant tumors. From a therapeutic point of view, surgery for the
      obstruction of the lower urinary tract (TURP or retropubic prostatectomy) may be
      necessary, as well as the cyclophosphamide based polychemotherapy with
      corticosteroids and other cytostatic agents, and radiotherapy; intratecal
      chemotherapy has also been used adjuvant bone marrow transplantation.

PMID- 16903561
TI  - [Mesenteric lymphangiomatosis. Case report].
AB  - OBJECTIVE: Lymphangiomas are lesions usually presenting during childhood and are
      located mainly in the head and neck region; less than 5% are intraabdominal.
      Lymphangiomatosis is the term used for multifocal or diffuse lymphangiomas.
      METHODS AND RESULTS: We report the case of a mesenteric lymphangiomatosis
      presenting as an acute abdomen in a 19-year-old man, review the literature and
      discuss the clinical management of these patients. CONCLUSIONS: Prognosis and
      treatment of these lesions depends of its site of origin and extension, being
      complete surgical excision the optimal treatment.

PMID- 16903562
TI  - [Right renal mass with thrombus in supradiaphragmatic vena cava].

PMID- 16903563
TI  - [Unusual iconography of metastasis of bladder infiltrating transitional
      carcinoma].

PMID- 16903564
TI  - Urethral and vaginal infections, age of patients and state of the pelvic floor in
      the aetiology of the irritative symptoms of the lower urinary tract in women.
AB  - OBJECTIVES: The aim of this study was to evaluate the importance of a) urethral
      and/or vaginal infections caused by common germs or Mycoplasmas, Chlamydia,
      Candida; b) age of patients; c) pelvic floor disorders in the development of
      irritative urinary symptoms in women. METHODS: 77 consecutive abacteriuric
      symptomatic female patients were compared with 55 asymptomatic women. A detailed
      micturition history and a genitourinary physical examination were performed.
      Urine samples as well as vaginal and urethral swabs were taken for cultures.
      RESULTS: No statistical difference was found between the two groups regarding
      both urethral and/or vaginal infections and pelvic floor disorders. Whereas a
      significant statistical difference was found in the age of the patients. In the
      symptomatic group the women were older than in the asymptomatic group.
      CONCLUSIONS: The results of this study confirm that ageing is a very important
      cause in the development of the lower urinary tract symptoms in women.

PMID- 16903565
TI  - [Acute nursing].

PMID- 16903566
TI  - [Questions about rationing are not worth answering].

PMID- 16903567
TI  - [Quality is more important in grant-giving].

PMID- 16903568
TI  - [Negotiations must be cultivated].

PMID- 16903569
TI  - [Professional information lessens anxiety].

PMID- 16903571
TI  - ["Dhaka-combinations" to prevent diarrhea].

PMID- 16903570
TI  - [Local antiseptics in the treatment of wounds].

PMID- 16903572
TI  - [Dr H. Umbug and Isidor Schlau].

PMID- 16903573
TI  - [Searching for continuing education].

PMID- 16903574
TI  - [Impertinent, impatient, influential].

PMID- 16903575
TI  - [Instant-years: a new path].

PMID- 16903576
TI  - [A forum for nursing...a demonstration].

PMID- 16903578
TI  - [I have always pushed everyone to utilize his maximum potential].

PMID- 16903577
TI  - [Violent or violence: what is the difference?].

PMID- 16903579
TI  - [Competence and flexibility through a solid professional profile].

PMID- 16903580
TI  - Shattering the consensus on end-of-life care: was the Schiavo case palliative
      medicine's Humpty Dumpty?

PMID- 16903581
TI  - Terri Schiavo and the use of artificial nutrition and fluids: insights from the
      Catholic tradition on end-of-life care.

PMID- 16903582
TI  - Narratives of grief and their potential for transformation.
AB  - This article examines narratives of grief and loss and how, under the best of
      circumstances, they may lead to transformation and growth, even contributing to
      the greater social good. Using psychodynamic and narrative theories, and examples
      drawn from mourners who have used their grief in powerful and political ways, I
      make the case that even grief that has been highly appropriated and contested, as
      in the case of Terri Schiavo, may ultimately serve important functions. Grief may
      mobilize mourners by helping them to turn passivity into activity. Grief may
      mobilize higher-level defenses such as altruism. Grief and loss may lead to a
      mourner's desire to do for others what was not done for him or her. A necessary
      part of turning grief into social action is the creation of a coherent grief
      narrative-first personal and then political. This coherent narrative can be
      developed using clinical interventions as well. Hence I discuss the clinical
      implications of helping those who are grieving to create coherent narratives out
      of shattered assumptions in a process of personal and social change.

PMID- 16903583
TI  - Can we know what Terri Schiavo would have wanted?
AB  - What would Terri Schiavo have wanted? That remains an unanswered question for
      many who followed the media frenzy that attended the extraordinary court and
      legislative battles that preceded her death 13 days after her feeding tube was
      removed for the last time. What would she have directed her physicians to do if
      she had "miraculously" regained capacity and awareness of the consequences of her
      cardiac arrest that left her in a persistent vegetative state? Who would she have
      wanted to make that decision for her if she were unable to do so? How are we to
      understand the meaning of statements that she purportedly made about life
      sustaining treatments approximately 20 years ago, and how can we apply them to
      the current situation? This article reflects on those questions from the
      perspective of two small exploratory studies. These studies considered the
      meanings and interpretation of statements by terminally ill patients concerning
      desire for hastened death and the relevance of previously made statements to
      their current clinical situation.

PMID- 16903584
TI  - Artificial nutrition and hydration at the end of life: ethics and evidence.
AB  - The case of Terri Schiavo resulted in substantial media attention about the use
      of artificial nutrition and hydration (ANH) especially by percutaneous endoscopic
      gastrostomy (PEG). In this article, I review ethical and legal principles
      governing decisions to choose or forgo ANH at the end of life, including issues
      of autonomy and decision-making capacity, similarities and differences between
      ANH and other medical treatments, the role of proxies when patients lack decision
      making capacity, and the equivalence of withholding and withdrawing treatment.
      Evidence for palliative or life-sustaining benefits for ANH are reviewed in three
      disease processes: amyotrophic lateral sclerosis (ALS), cancer, and dementias,
      including Alzheimer's disease. Although more recent studies suggest a possible
      palliative role for ANH in ALS and terminal cancer, feeding tubes do not appear
      to prolong survival or increase comfort in advanced dementia of the Alzheimer's
      type.

PMID- 16903585
TI  - Legal and policy lessons from the Schiavo case: is our right to choose the
      medical care we want seriously at risk?
AB  - The article explores the individual patient's right to refuse, withdraw, or
      insist on medical treatment where there is conflict over these issues involving
      health care personnel or institutions, family members, legal requirements, or
      third parties concerned with public policy or religious/ideological/political
      interests. Issues of physician assistance in dying and medical futility are
      considered. The basis and the current legal status of these rights is examined,
      and it is concluded that threats to the autonomy of patients, to the privacy of
      the doctor/patient relationship, and to the quality of medical care should be
      taken seriously by individuals, medical practitioners, and others concerned with
      developing and maintaining reasonable, effective, and ethical health care policy.

PMID- 16903586
TI  - End-of-life issues in elderly patients.
AB  - OBJECTIVE: To describe elderly-specific issues in end-of-life care. METHODS:
      Literature review and case examples. RESULTS: There is great heterogeneity in
      elderly patients' responses to end-of-life care. SIGNIFICANCE OF RESULTS:
      Developmental and individual issues need to be considered in end-of-life
      discussions.

PMID- 16903587
TI  - "A rose for Emily," a rose for Terri: the lifeless body as love object and the
      case of Theresa Marie Schindler Schiavo.
AB  - The precise circumstances of Theresa Schiavo's disability, the reasons advanced
      for preserving and ending her life and the covert personal agendas and
      unacknowledged political-economic forces that may have significantly affected the
      outcome were investigated and are presented.

PMID- 16903589
TI  - Development of a spiritual pain assessment sheet for terminal cancer patients:
      targeting terminal cancer patients admitted to palliative care units in Japan.
AB  - OBJECTIVE: This research explores the potential benefit of a spiritual pain
      assessment sheet to clinical practice. With spiritual pain defined as "pain
      caused by extinction of the being and meaning of the self," the spiritual pain
      assessment sheet was developed by Hisayuki Murata from his conceptual framework
      reflecting the three dimensions of a human being as a being founded on
      temporality, a being in relationship, and a being with autonomy. The assessment
      sheet was developed from reviews of the literature and examinations from a
      philosophical perspective on the structure of spiritual pain. METHODS: Patients
      admitted to palliative care units in Japan were interviewed using the assessment
      sheet. The responses were analyzed qualitatively. The usefulness of the
      assessment sheet and the burden placed on the patients by its use were also
      investigated. RESULTS: The spiritual pain elucidated by the assessment sheet was
      the same as that revealed in the earlier research of Morita. The patients
      reported that they did not find the use of the assessment sheet a burden, and
      more than half reported that it was useful. The burden of the assessment sheet on
      the subjects was thus determined to be low. Positive feedback on the assessment
      sheet was also received from the nurses who conducted the patient interviews, who
      said the assessment sheet made it easier to talk with the patients about their
      spiritual pain. SIGNIFICANCE OF RESEARCH: The research results indicate that the
      spiritual pain assessment sheet provided an appropriate assessment of spiritual
      pain among terminal cancer patients, showing that such a sheet could be used as
      an assessment tool in the future.

PMID- 16903588
TI  - Affirming the right to care, preserving the right to die: disorders of
      consciousness and neuroethics after Schiavo.
AB  - In this article, I attempt to untangle some of the cultural, philosophical, and
      ethical currents that informed the Schiavo case. My objective is to better
      apprehend what the Schiavo case means for end-of-life care in general and to
      assert that our discourse about the ethical issues attendant to brain injury will
      be impoverished if we limit our discussions about disorders of consciousness
      solely to the vegetative state. If we ignore emerging developments in
      neuroscience that are helping to elucidate the nature of these disorders and fail
      to broaden the conversation about brain injury, beyond the unmitigated futility
      of the permanent vegetative state, we will imperil others who might improve and
      be helped. Through such efforts we can help mitigate the tragedy of the Schiavo
      case and overcome the rhetoric that marked the national discourse in March 2005.
      Once the complexity of disorders of consciousness is appreciated, rhetorical
      statements about a right to die or a right to life are exposed as being
      incompatible with the challenge of providing care to such patients. This is
      especially true as neuroscience brings greater diagnostic refinement to their
      assessment and management, a topic addressed in this article, which specifically
      focuses on the clinical and ethical implications of the recently described
      minimally conscious state. Instead of staking out ideological positions that do
      not meet the needs of patients or families, we should strive to both preserve the
      right to die for those who are beyond hope while affirming the right to care to
      those who might benefit from coming advances in neuroscience. If we can achieve
      that delicate balance, we will be able to transcend the partisan debate that
      shrouded the life and death of Theresa Marie Schiavo and begin to articulate a
      palliative neuroethics of care for those touched by severe brain injury and
      disorders of consciousness.

PMID- 16903590
TI  - Caring for the spiritual pain of patients with advanced cancer: A
      phenomenological approach to the lived experience.
AB  - OBJECTIVE: The aim of this research was to reveal, from the perspective of the
      "lived experience" shared by cancer patients and their nurses, how patients
      facing death create lived experience in the context of palliative care. This
      research also aims to elucidate the meaning nurses find in patients' experiences
      while caring for their patients. METHODS: The participants in this study were
      cancer patients who were given opportunities to discuss events and concerns in
      their daily lives, with the interactions guided by the researchers.
      Transcriptions of conversations with the patients were analyzed using the method
      for empirical data classification set forth by Giorgi (1985) with appropriate
      modification. RESULTS: This study found that when the nurse correctly interprets
      the meaning of the concerns (Heidegger, 1962) of the patient facing death and
      shares that meaning with the patient, fundamental questions naturally arise for
      the patient. Answering these questions becomes possible only through interactions
      that require the reexamination of the values of the patient and the nurse.
      SIGNIFICANCE OF RESEARCH: This research elucidates the spiritual pain experienced
      by cancer patients and discusses opportunities for nurses to address the
      spiritual care of these patients.

PMID- 16903591
TI  - Of rats and men: A narrative journey.
AB  - Palliative care clinicians are often challenged in this evidence-based world to
      find studies that are generalizable to our population. And yet, there is much to
      be learned from the unique situations that we encounter. This narrative reflects
      upon the application of palliative principles to one special rat model.

PMID- 16903592
TI  - [Effect of rolling needle therapy on quality of life in the patient of non
      organic chronic insomnia: a randomized controlled trial].
AB  - OBJECTIVE: To probe therapeutic effect of rolling needle therapy on insomnia and
      standardize the therapeutic program. METHODS: Multi-central randomized blind
      controlled trials were used, and 180 cases were randomly divided into a rolling
      needle group and a medication group, 90 cases in each group. The rolling needle
      group were treated with rolling needle therapy at the Urinary Bladder Channel
      line 1 and 2 at the back and the Governor Vessel, and the medication group with
      clonopin 4-6 mg, for 4 weeks. Effective rates for sleep disturbance improvement
      and Spitzer index of life quality were evaluated after 4 weeks' treatment and 3
      months' follow-up. RESULTS: The effective rate was 82.2% in the rolling needle
      group and 60.0% in the medication group with a significant difference between the
      two groups (P < 0.05), and with a significant difference between the two groups
      in Spitzer index of life quality (P < 0.05). After 3 months' follow-up, the
      effective rate was 40.0% in the rolling needle group and 30.3% in the medication
      group with no significant difference between the two groups (P > 0.05), and there
      was a significant difference between the two groups in Spitzer index of life
      quality. CONCLUSION: Rolling needle therapy can treat chronic insomnia and
      increase life quality of the patient.

PMID- 16903593
TI  - [Effect of skull acupuncture and scalp acupuncture on serum vascular endothelial
      growth factor in the patient of acute cerebral infarction].
AB  - OBJECTIVE: To investigate effect of skull suture acupuncture (skull acupuncture)
      and scalp acupuncture on serum vascular endothelial growth factor (VEGF) in the
      patient of acute cerebral infarction (CI). METHODS: Twenty cases of CI were
      treated with skull suture acupuncture at coronal suture, sagittal suture,
      lambdoid suture, etc. combined with medication (group B), group C (n=20) with
      scalp acupuncture at contralateral Dingnie Qian-xiexian (MS 6) and Dingnie
      Houxiexian (MS 7) plus medication, and group A (n=20) with medication. Changes of
      serum VEGF contents were investigated in the three groups. RESULTS: After
      treatment, the serum VEGF content did not significantly change in group A (P >
      0.05), and significantly increased in group B and group C (P < 0.01, P < 0.05),
      with significant difference as group B and C compared with that of group A (P <
      0.05), and with no significant difference between group B and group C (P > 0.05).
      CONCLUSION: Skull suture acupuncture combined with medication and scalp
      acupuncture plus medication have a similar effect on serum VEGF in the patient of
      acute cerebral infarction.

PMID- 16903594
TI  - [Clinical observation on combined acupuncture and moxibustion therapy for
      treatment of 160 cases of polyneuritis].
AB  - OBJECTIVE: To observe clinical therapeutic effect of combined acupuncture and
      moxibustion therapy on polyneuritis. METHODS: One hundred and sixty cases were
      treated with combined scalp acupuncture, body acupuncture (stimulating root of
      nerve as main), cupping and pricking at segmental root of nerve, and electric hot
      moxibustion, and their therapeutic effects were observed. RESULTS: One hundred
      and thirty-eight cases were cured (86.3%) and the total effective rate was
      100.0%. The average recovery time for clinical symptoms was 12.81 days, the
      average recovery time for nervous system signs was 19.76 days, the average
      recovery time for recovery of ocular muscular dyskinesia was 15.14 days. There
      was significant therapeutic effect for improvement of simple symptoms, with
      significant differences when the first and second therapeutic courses compared
      with that before treatment (P < 0.01). CONCLUSION: The combined acupuncture and
      moxibustion therapy has a definite therapeutic effect on polyneuritis.

PMID- 16903595
TI  - [Incidence rate and acupuncture-moxibustion treatment of post-stroke depression].
AB  - OBJECTIVE: To understand the incidence of post-stroke depression (PSD) and the
      therapeutic effect of acupuncture-moxibustion. METHODS: Five hundred and sixty
      cases were rating with Hamilton depression scale, and lesion parts, gender, age
      and property of stroke between the PSD and non-PSD were compared by analysis of
      variance, chi2 test, and then the patients of PSD were randomly divided into two
      groups and treated respectively with Prozac-20 and acup-moxibustion at Sishencong
      (EX-HN 1), Anmian, Neiguan (PC 6), Shenmen (HT 7), Zusanli (ST 36), Sanyinjiao
      (SP 6), Taichong (LR 3), Zhaohai (KI 6), Shenmai (BL 62). RESULTS: The total
      incidence rate of PSD was 43.9%, with no relation to the lesion parts, gender,
      age and property of stroke (P > 0.05), and there were very significant
      differences in HAMD scores before and after treatment in the two groups (P <
      0.0001), with no significant difference in the effective rate between the two
      groups (P > 0.05). CONCLUSION: PSD has a high incidence and influences the
      recovery of nervous function, and it should be treated at early stage. Acup
      moxibustion and Prozac-20 have similar therapeutic effect.

PMID- 16903596
TI  - [Clinical observation on acupuncture plus laser radiation for treatment of facial
      spasm].
AB  - OBJECTIVE: To search for a convenient, safe and effective method for treatment of
      facial spasm. METHODS: Three hundred and ninety cases of facial spasm were
      divided into 2 groups in order of visiting: medication group of 200 cases were
      treated with routine medicine, and acupuncture and laser treatment group of 190
      cases treated with acupuncture plus laser radiation. After treatment of 30 days,
      their therapeutic effects were summarized. RESULTS: The total effective rate, the
      cured rate and the 6-month recurrence rate were 93.7%, 64.7%, 6.7% in the
      acupuncture and laser treatment group, and the corresponding figures were 62.0%,
      32.0% and 33.9% in the medication group respectively, with a very significant
      difference between the two groups in the therapeutic effect (P < 0.01).
      CONCLUSION: Acupuncture plus laser radiation is a convenient and safe method for
      treatment of facial spasm.

PMID- 16903597
TI  - [Observation on therapeutic effects of scraping therapy and warming acupuncture
      moxibustion on 50 cases of fasciitis of back muscles].
AB  - OBJECTIVE: To search for the best method for treatment of fasciitis of back
      muscles. METHODS: One hundred cases of fasciitis of back muscles were randomly
      divided into two groups. The treatment group of 50 cases were treated with
      scraping and warming acupuncture and moxibustion at Fengmen (BL 12), Feishu (BL
      13), Quyuan (SI 13), Bingfeng (SI 12), Jiafeng, local pressure pain points, and
      cord-like node; and the control group of 50 cases with simple acupuncture.
      RESULTS: In the treatment group, 40 cases were cured and 10 cases improved with a
      total effective rate of 100.0%; in the control group, 26 cases were cured and 16
      cases improved, 8 cases were ineffective with a total effective rate of 84.0%.
      The treatment group in improvement of pressure pain and pain was better than the
      control group, with scores significantly decreased (P < 0.01). CONCLUSION:
      Scraping therapy and warming acup-moxibustion have obvious effect on fasciitis of
      back muscles, and it is a better therapy for this disease.

PMID- 16903598
TI  - [Analysis on therapeutic effect of substance-partitioned moxibustion at Guanyuan
      (CV 4) and shenque (CV 8) for treatment of primary dysmenorrhea of cold-damp
      type].
AB  - OBJECTIVE: To observe clinical therapeutic effect of substance-partitioned
      moxibustion on primary dysmenorrhea (PD). Methods One hundred and thirty-eight
      cases of PD were randomly divided into two groups, the treatment group (n=78)
      were treated with substance-partitioned moxibustion at Guanyuan (CV 4) and
      Shenque (CV 8), once a day; and the control group (n=60) treated with oral
      administration of Yueyueshu Powder, twice a day, 10 g each time. They were
      treated for 3 menstrual cycles. RESULTS: The total effective rate and the index
      of therapeutic effect were 96.1% and 90.8% in the treatment group, and 88.3% and
      76.2% in the control group, respectively, with a significant difference between
      the two groups (P < 0.05). CONCLUSION: Clinical therapeutic effect of substance
      partitioned moxibustion on primary dysmenorrhea is obvious.

PMID- 16903599
TI  - [Study on angle and depth of needle insertion in acupuncture at Zusanli (ST 36)].
AB  - OBJECTIVE: To provide an appropriate angle and depth of needle insertion in
      acupuncture at Zusanli (ST 36) and avoid injuring the nerve and blood vessel and
      exert the most effect. METHODS: Eighty adult lower-limb samples were used to
      dissect and observe the relative layered structures and adjoining important
      nerves and blood vessels in needling Zusanli (ST 36) according to the national
      standard. RESULTS: The needling depth from the skin to the interosseous membrane
      and from the skin to posterior border of tibialis posterior is (2.22 +/- 0.31) cm
      and (4.42 +/- 0.53) cm, respectively. There are flabellate branches of anterior
      tibial arteries and deep peroneal nerves around the needle in the superficial
      layer of interosseous membrane. The vessel and nerve bundles containing tibial
      nerve and posterior tibial vessels can be touched when the needle body past
      through tibialis posterior. CONCLUSION: It is recommended that ideal average
      depth of acupuncture is 2.22 cm and the maximum depth is 4.42 cm for oblique
      needling Zusanli (ST 36). When it is injected, the needle should be
      perpendicularly inserted or deviated slightly to the direction of tibia and
      paralleled to medial surface of tibia. And the safe needling depth is generally
      less than 5 cm. The point of the body surface between tibialis anterior and
      extensor digitorum longus at 3 cun below Dubi (ST 35) is also an effectively
      stimulating point.

PMID- 16903600
TI  - [New explaination of mechanisms of indications of Suliao (GV 25) and Shuigou (GV
      26)].
AB  - OBJECTIVE: To newly explain mechanisms of indications of Suliao (GV 25) and
      Shuigou (GV 26). METHODS: Analyze mechanisms of indications of Suliao (GV 25) and
      Shuigou (GV 26) in TCM "viscera-state doctrine" as the center and in combination
      with anatomy of western medicine. RESULTS: Not only put forward the corresponding
      relation ("re-preparation" of external forms) of the five sense organs with five
      solid organs, and also use this theory to explain the reasons why Suliao (GV 25),
      Shuigou (GV 26) and round some extra-ordinary points (Bijian, Bizhonggou) have
      same indications. CONCLUSION: This thinking has guiding significance for
      developing new acup-moxibustion treatment points and determining the angle and
      direction of needling.

PMID- 16903601
TI  - [Differentiation and analysis of original meaning of classical channel theories].
AB  - OBJECTIVE: To probe into the original meanings of manifestation and root cause,
      root and knot, Genliu infusion, Benshu, pathway of qi, four sea, Guan-He Shu and
      other classical channel theories. METHODS: Based on Huangdi Neijing (The Yellow
      Emperor's Internal Classic) and other classical literatures, combined with
      medical books in bamboo slip and the silk and opinions of annotation experts of
      successive dynasties, deeply analyze and study. RESULTS: Classical channel
      theories are involved in some theories of channel structures, with 3 original
      meanings: expounding the origin, the end and running of channels, expounding bi
      directional running of channel-qi, and expounding the affinity relation of six
      channels, six qi, six zang-organs and six fu-organs. CONCLUSION: Classical
      channel theories stress emphasize concentric running of channels, and concentric
      arrangement of channel acupoints, bi-directional running of channel-qi, and each
      affinity of six channels.

PMID- 16903602
TI  - [Observation on therapeutic effects of centro-square needling and triple needling
      on ankylosing spondylitis].
AB  - OBJECTIVE: To probe therapeutic effects of centro-square needling and triple
      needling on ankylosing spondylitis. METHODS: Sixty cases of spondylitis were
      randomly divided into a treatment group and a control group. The treatment group
      were treated with centro-square needling and triple needling, and the control
      group with routine acupuncture therapy, with motortherapy combined in the two
      groups. RESULTS: Both the therapeutic methods were effective, but the therapeutic
      effect in the treatment group was significantly better than that in the control
      group (P < 0.05). CONCLUSION: Acupuncture combined with motortherapy has definite
      therapeutic effect on ankylosing spondylitis, with centro-square needling and
      triple needling having better therapeutic effect.

PMID- 16903603
TI  - [Observation on therapeutic effects of red-hot needle therapy on nodules of
      breast of the type of stagnation of liver-qi and phlegm coagulation].
AB  - OBJECTIVE: To compare therapeutic effects of red-hot needle therapy and filiform
      needle therapy on nodules of breast of the type of stagnation of liver-qi and
      phlegm coagulation. METHODS: Six hundred cases were randomly divided into a
      treatment group and a control group, 300 cases in each group. The treatment group
      were treated with red-hot needle pricking at the proliferative parts and Ashi
      points as main, and the control group with filiform needle therapy. RESULTS: In
      the treatment group, 240 cases were cured, 58 cases improved and 2 cases were not
      cured with an effective rate of 99.3%; and in the control group, 113 cases were
      cured, 165 cases improved and 22 were not cured with an effective rate of 92.7%,
      with a significant difference between the two groups (P = 0.001). CONCLUSION: The
      therapeutic effect of red-hot needle therapy is better than that of filiform
      needle therapy on nodules of breast of the type of stagnation of liver-qi and
      phlegm coagulation.

PMID- 16903604
TI  - [Changes of IFN-gamma, IL-2, IL-6 and IL-10 in the patient with cardiac surgery
      under combined acupuncture anesthesia].
AB  - OBJECTIVE: To observe the effect of electroacupuncture (EA) on cytokines in the
      cardiac surgical patient and to evaluate the application of combined acupuncture
      anesthesia to cardiac surgery. METHODS: Thirty patients with atrial septal defect
      were divided into 3 groups, general anesthesia group (A), acupuncture anesthesia
      group (B) and combined general anesthesia and EA group (C). Peripheral blood
      samples were collected before anesthesia, before cardiopulmonary bypass (CPB), 30
      min after CPB and 24 h after operation to determine the levels of interferon
      gamma (IFN-gamma), interleukin-2 (IL-2), IL-6 and IL-10. RESULTS: The levels of
      IFN-gamma and IL-2 decreased in the 3 groups after CPB and further decreased 24 h
      after operation, and in the group C were higher than those in the group B. The
      levels of IL-6 and IL-10 significantly increased 24 h after operation in the 3
      groups with no significant difference among the 3 groups. CONCLUSION: The general
      anesthesia combined with EA can not completely improve the decrease of IFN-gamma
      and IL-2 induced by CPB, indicating that the good response of the general
      anesthesia combined with EA to stress can partially improve the immunosupression
      induced by CPB. Acupuncture does not have significant effect on inflammatory
      cytokine reaction induced by cardiac surgery.

PMID- 16903605
TI  - [Study on evaluation index of acupoint transdermal administration--drug delivery
      coefficient].
AB  - OBJECTIVE: To investigate the correlation of skin electric resistance changes
      with the blood drug content in acupoint transdermal administration, and to
      establish an new evaluation index for drug delivery efficiency through acupoints.
      METHODS: Twenty-four rabbits were randomly divided into an observation group and
      a control group. In the observation group, aminophylline was administrated
      through "Feishu" (BL 13), "Geshu" (BL 17) and "Danzhong" (CV 17) which are
      commonly used for treatment of bronchial asthma, and the control group through
      sham-points on the back. The skin resistance and plasma aminophylline content
      were determined after application of aminophylline to the points, and their
      changes with time were observed. The ratio of Css/Rss at stability was defined as
      delivery coefficient (DC) which reflects the efficiency of delivering drug at
      acupoints and sham acupoints. RESULTS: Both the plasma aminophylline and the skin
      resistance value tended to steady about 6-8 h after application of
      aminophyiophylline. The DC in the acupoints was higher than that in the sham
      acupoints (P < 0.01). And there was significant difference as DC of the
      "Feishu"was significant difference (BL 13) and "Danzhongas DC of the "Feish"
      (BLCV 17) compared with that of "Geshu" (BL 17) (P < 0.01). CONCLUSION: The
      bigger the DC is, the higher the efficiency of drug delivery is; the efficiency
      of drug delivery through acupoints is higher than that through sham-acupoints.

PMID- 16903606
TI  - [Effects of acupoint thread implantation and Chinese herb on PTH and TGF-beta1 in
      the rate of chronic renal failure].
AB  - OBJECTIVE: To probe into the mechanisms of thread implantation at Zusanli(ST 36)
      and Chinese herbs in treatment of chronic renal failure(CRF). METHODS: CRF rat
      model was made by Platt subtotal nephrectomy. They were divided into 5 groups,
      sham operation group, model group, Chinese herbs group, thread implantation group
      and thread implantation plus Chinese herbs group. After treatment of 8 weeks,
      serum parathyroid hormone (PHT), transforming growth factor beta1 (TGF-beta1)
      expression in residual renal cells, malondialdehyde(MDA) content in the residual
      renal tissue, serum urea nitrogen(BUN) and creatinine(Scr), protein in urine and
      pathological changes were investigated. RESULTS: The above indexes after
      treatment by thread implantation at acupoint, Chinese herbs, and acupoint thread
      implantation plus Chinese herbs showed begin reversion, especially, the most
      obviously improvement in the acupoint thread implantation plus Chinese herbs
      treatment group. CONCLUSION: The mechanism of acupoint thread implantation and
      Chinese herbs in improvement of CRF is related with decrease of PTH, inhibition
      of TGF-beta1 expression, decrease of MDA content and resisting lesion of renal
      fibrosis.

PMID- 16903607
TI  - [Essences of Mr. Xie Xi-liang's acupuncture experience].
AB  - Mr. Xie Xi-liang studied acupuncture from Mr. Cheng Dan-an in his early years. He
      has been engaged in clinical and teaching work of acupuncture and moxibustion for
      near 60 years. He attaches importance to basic training of acupuncture and
      moxibustion, advocates carefully choice of acupoints clinically, lays stress on
      using acupuncture and moxibustion to treat diseases, especially using direct
      moxibustion. He is good at deeply needing Fengfu (GV 16) to treat mental
      diseases. He has very rich knowledge and experience, and he deserves to be
      studied for younger generation.

PMID- 16903608
TI  - [Legislation and development of traditional Chinese medicine in Victoria State of
      Australia].
AB  - This paper introduces the process of legislation of TCM in Victoria state of
      Australia, and expounds the significance of TCM legislation, and emphasizes that
      only TCM legislates, can it develops; and only standard TCM, can a good figure
      set up in people and larger contribution be made for human health.

PMID- 16903609
TI  - [Design and application of a cone-shaped warming-acupuncture-moxibustion
      apparatus].
AB  - To design a warming acupuncture-moxibustion apparatus suitable to warming
      acupuncture therapy and easily attaching to the filiform needle handle. The
      apparatus consists of a container for moxa, a tray and regulative clips. The
      container for moxa is for store of moxa-wool without bottom and it can prevent
      moxa fire and ash from dropping and burning the skin of the patient or the
      clothes; the tray with holes on it can serve as a support of the moxa in the
      container, and can control the moxa burning and heat radiation; the clips can
      adjust the distance between the cone and the skin. With the advantages of handy
      material, easy installation, lower cost, and convenient operation, the apparatus
      is worthy of clinical application and popularization.

PMID- 16903610
TI  - [Discussion on reinforcing-reducing method by lifting and thrusting the needle
      and slow-rapid reinforcing-reducing method from the point of view of energy].
AB  - OBJECTIVE: To resolve the contradictory in expounding of reinforcing and reducing
      by lifting and thrustion the needle and slow-rapid reinforcing and reducing
      method. METHODS: In a certain condition,the relationship between the external
      force (the joint force of both the pressing on the force pressing on the needle
      and the force arresting the needle's moving) and the speed of needle's moving is
      deduced by means of kinetic energy theorem, so, when the needle is heavily thrust
      or lifted, the speed of its moving will be increased. CONCLUSION: In the
      reinforcing and reducing method by lifting and thrusting the needle, "heavily"and
      "gently" of heavily thrustiing and gently lifting or gently thrusting and heavily
      lifting should be considered as differences of the amplitudes of lifting and
      thrusting the needle; "slow-rapid" of slow-rapid reinforcing and reducing method
      should be considered as difference of the speeds.

PMID- 16903611
TI  - [Thinking about increasing therapeutic effect of acupuncture and moxibustion for
      slimming].
AB  - OBJECTIVE: To probe into the factor of increasing the therapeutic effect of
      acupuncture and moxibustion for slimming. METHODS: The factors of increasing the
      therapeutic effect of acupuncture and moxibustion for slimming were thought by
      analysis of the physician and the patient, and combination of theory with
      clinical treatment, and opinions were put forward. CONCLUSION: There are a lot of
      factors influencing the therapeutic effect of acupuncture and moxibustion for
      slimming, and only both the physician and the patient cooperate each other and
      pay attention to the factors, can the therapeutic effect be better increased.

PMID- 16903612
TI  - [Selection of acupoints in acupuncture-moxibustion for drug abstinence].
AB  - Selection (screening) of acupoints, clinical application of acupoints and
      mechanisms of acupoints in treatment of acupuncture and moxibustion for drug
      abstinence in recent 10 years are reviewed, considering that the studies of
      acupuncture and moxibustion for drug abstinence are not enough in the width and
      depth, especially, lacking deep studies in selection (screening) of acupoints,
      clinical application of acupoints and the mechanisms. The acupuncture and
      moxibustion for drug abstinence is a newer field, in future the systematically
      and scientifically clinical and experimental studies on the acupuncture and
      moxibustion for drug abstinence should be strengthened, especially, the studies
      on clinical application of acupoints.

PMID- 16903613
TI  - Age group and health status effects on health behavior change.
AB  - The authors explored health behavior change during 5 years, considering
      age/cohort, health status, and gender effects. The authors divided the sample (n
      = 1,064) into 4 age/cohort groups: young adults (n = 139; 19-42 years), middle
      aged adults (n = 386; 43-62 years), young-old adults (n = 296; 63-72 years), and
      old-old adults (n = 243; 73+ years) and health status: cardiovascular disease and
      physical disability. Smoking and seat belt behaviors remained stable, whereas
      alcohol, food consumption, food preparation, physical activity, dental, and
      medical behaviors showed change. Change in health behaviors differed by
      age/cohort group and health status for food consumption, food preparation, and
      medical care, primarily showing negative change for old-old adults and positive
      change for individuals with cardiovascular disease. Health behavior interventions
      need to focus on the old-old, individuals with physical disability, and on
      smoking and seat belt use. These specific populations and behaviors need to be
      targeted to promote positive health behavior change, to limit future onsets of
      disability and morbidity, and to prevent the occurrence of premature death.

PMID- 16903614
TI  - Smoking cessation 1: pharmacological treatments.
AB  - In part 1 of this 3-part review of interventions for tobacco dependence, the
      authors present evidence regarding the efficacy of pharmacological treatments for
      smoking cessation. They also present evidence and recommendations included in the
      U.S. Department of Health and Human Services Treating Tobacco Use and Dependence:
      Clinical Practice Guideline (the Guideline), evidence from studies published
      after the Guideline, and recommendations of their own. The authors review
      nicotine replacement therapies, antidepressants, and other pharmacotherapies,
      followed by pharmacological treatments for special populations. The evidence
      indicates that a variety of effective smoking cessation medications are
      available. First-line medications include nicotine replacement therapies and
      bupropion. Pharmacotherapy is a vital component of smoking cessation
      interventions and should be offered to all smokers who want to quit unless
      contraindicated. There is a need for further research on pharmacotherapies for
      smoking cessation, and the authors discuss key areas for future research.

PMID- 16903615
TI  - Social cognitive predictors of sun protection intention and behavior.
AB  - The authors investigated sunbathing behavior and intention prospectively using
      the Theory of Planned Behavior (TPB). Before summer, 85 young adults who intended
      to sunbathe completed a TPB questionnaire. After summer; 46 of them completed a
      second questionnaire about their summertime sunbathing behavior The proposed
      model was successful in predicting both behavior and intention to use sun
      protection, with 45% of the variance of self-reported sunscreen use and 32% of
      the variance in intention explained by the TPB. Items designed to measure self
      efficacy and perceived control loaded onto different factors and demonstrated
      discriminant validity. Self-efficacy predicted both intention and behavior (after
      controlling for all other TPB variables), but perceived behavioral control did
      not. The authors discuss the implications of the findings for potential
      interventions to improve sun protection behavior

PMID- 16903616
TI  - To hospitalize or not to hospitalize? That is the question: an analysis of
      decision making in the nursing home.
AB  - The authors examined the processes and factors that influence physicians'
      decision-making processes as regarding hospitalization of nursing home residents.
      In a large nonprofit nursing home, 6 full-time male physicians and 1 female nurse
      practitioner completed questionnaires that described the medical decision-making
      process for 52 nursing home residents for whom hospitalization was considered.
      The questionnaire covered the following topics: medical event description, the
      decision-making process, considerations in making treatment decisions, and the
      role of advance directives. Hospitalized residents had fewer treatments
      considered and fewer treatments chosen than those who were not hospitalized.
      Residents with fractures were the most commonly hospitalized residents, whereas
      residents in frailer conditions, with breathing problems, and for whom the
      physician considered quality of life to be most important were less likely to be
      hospitalized. The results of this study clarify the complexity of factors
      affecting the decision-making process and suggest a methodology that may assist
      in discerning those factors in the future.

PMID- 16903617
TI  - Management of dyslipidemia in renal disease and transplantation.

PMID- 16903618
TI  - Renal fibrosis, origin and possible interventions: a time for action.

PMID- 16903619
TI  - Switching immunosuppressive drugs in kidney transplant recipients: "show me the
      evidence".

PMID- 16903620
TI  - Acute renal failure in children: etiology, treatment and outcome.
AB  - Children with acute renal failure (ARF) may be treated in pediatric renal or
      intensive care (PICU) units where there is an increasing use of continuous renal
      replacement therapies such as hemofiltration (HF). Over three years, we
      prospectively recorded details of all patients with ARF treated both within our
      regional pediatric renal unit, in two local neonatal intensive care units
      (NICUs), and one PICU, which are all supported by our institution. Our study
      included eighty-three ARF patients (43% male) with a median age of 5.7 years
      (range 1 day - 19.8 years); 41% of patients were < 2 years, 20% 2-5 years, 13% 5
      10 years and 26% > 10 years of age. A total of 37 patients (45%) were treated in
      the renal unit versus 46 (55%) patients in NICU/PICU. The initial treatment
      modality was conservative in 33%, peritoneal dialysis (PD) in 23%, hemodialysis
      (HD) in 15%, HF in 28%, and isolated plasmafiltration in one percent of the
      patients. About 16% of the patients required more than one treatment modality.
      Outcome data at three months showed normal renal function in 49%, deaths in 20%,
      dialysis dependent disease in 14%, chronic renal failure (GFR < 60ml/min/1.73m2)
      in eight percent, and proteinuria and/or hypertension in seven percent of the
      patients. Only one (3%) death occurred in 37 patients treated in the renal unit
      compared to 16 deaths in 46 patients (35%) treated in the NICU/PICU. Our findings
      further confirm the low mortality rate with isolated renal failure and the
      substantial mortality and renal workload in intensive care areas where renal
      failure is often part of multi-organ failure. Further prospective studies will be
      required to analyze the impact of early hemofiltration in such patients.

PMID- 16903621
TI  - Attitude of physicians towards the follow-up of renal transplant patients: a
      questionnaire survey in Saudi Arabia.
AB  - The goal of this study was to evaluate the attitude of the physicians towards the
      follow-up of the renal transplant patients in the Kingdom of Saudi Arabia (KSA).
      We sent a questionnaire to 168 physicians working in 148 active dialysis centers
      in the KSA. The study was conducted from June-October 2005. There were 140
      physicians (83.3%) who answered the questionnaire; they represented 136 (91.9%)
      dialysis centers. There were 43 (31.2%) respondents who had a transplant clinic
      for follow-up of transplant recipients. Of the 96 (69.1%) who did not have a
      clinic, 29 (30.2%) claimed expertise for follow-up of transplant recipients, six
      (6.2%) had a laboratory set-up to monitor the immunosuppressive drug levels and
      40 (44.4%) felt the need for one. There were 121 (89%) respondents who would
      consider the chronic renal failure (CRF) patients for transplantation because it
      is the best form of therapy. Seventy-seven respondents (55%) had a protocol for
      work-up of the CRF patients for transplantation, 31 (22.3%) had a coordinator for
      the work-up of the transplant candidates, 34 (24.5%) had regular meetings to
      decide on the waiting list for transplantation, and 51 (37.8%) had affiliation
      with, or worked at a transplant center. Nevertheless, 127 (90.7%) respondents
      believed that the results of renal transplantation were good enough to recommend
      the procedure to all patients as early as possible. There were 133 (97.1%)
      respondents who believed that organ shortage was the major factor for the low
      percentage of renal transplantation. Only 52 (37.1%) respondents knew about the
      recent regulations established by the World Health Organization (WHO) for organ
      donation. There were 63 (48.1%) respondents who believed that seeking commercial
      renal transplantation outside the KSA to be unacceptable because of the medical
      and ethical complications involved. Many respondents (71.4%) from non-MOH
      hospitals, and those who had transplant clinics believed that the tacrolimus +
      mycophenolate combination was the most popular immunosuppressive regimen for
      renal transplant patients. Our survey suggests that the current practices
      concerning the work-up and follow-up of transplant patients in the dialysis
      centers in the KSA require refinement in terms of the need to enforce the use of
      a protocol to guide evaluation and therapy in each dialysis unit.

PMID- 16903622
TI  - Diagnostic value of Doppler ultrasound in differentiating prerenal azotemia from
      acute tubular necrosis in children.
AB  - Differentiating acute tubular necrosis (ATN) from prerenal azotemia is critical
      for selecting the appropriate treatment. This study was conducted to evaluate the
      diagnostic value of Doppler ultrasonography in differentiating ATN from prerenal
      azotemia in children. A total of 50 oliguric or anuric children with previous
      normal renal laboratory data were included. Doppler examination and calculation
      of resistive index (RI) was performed within 24 hours of admission and in the
      recovery phase of ARF. The sensitivity and specificity of RI in differentiating
      ATN from prerenal azotemia were assessed. At the cut-off point of RI = 0.75, the
      sensitivity and specificity of RI in differentiating prerenal failure and ATN was
      91.3% and 85.2%, respectively. We conclude that Doppler ultrasonography is
      helpful in differentiating ATN from prerenal azotemia in children. The cut-off
      value of 0.75 has the highest accuracy for this purpose.

PMID- 16903623
TI  - Influence of erythropoietin dose and albumin level on the plasma brain
      natriuretic peptide in hemodialysis patients.
AB  - Brain natriuretic peptide (BNP) levels increase in patients with congestive heart
      failure. Theoretically, BNP levels can be helpful in the determination of the
      "dry weight" of hemodialysis patients. To evaluate the effect of hemodialysis on
      the plasma concentration of BNP and to determine the factors that affect BNP
      levels during hemodialysis in patients with chronic renal failure, we studied
      five stable patients with chronic renal failure. A total of 15 blood samples were
      obtained for BNP levels at 24, 48 and 72 hours after the last hemodialysis
      session. The plasma BNP levels did not change significantly either with
      ultrafiltration volume or with time since last dialysis. However, the BNP levels
      correlated positively with the erythropoietin (EPO) dose (r=0.98, P<0.001) and
      negatively with the serum albumin levels (r = 0.94, P=0.02). Univariate analysis
      showed that the EPO dose (P=0.001) and the albumin level (P=0.02) were
      significant predictors of BNP level. Adjusted multivariate analysis showed
      significant interaction between the EPO dose and the albumin level (P=0.01,
      P=0.03 respectively. IN CONCLUSION: the plasma BNP levels were not significantly
      influenced by ultrafiltration volume or time since last dialysis. However, the
      BNP levels may be a useful prognostic parameter for assessing the risk of
      cardiovascular morbidity and mortality in hemodialysis patients.

PMID- 16903624
TI  - Survey of childhood enuresis in the Ehor community, the EDO State, Nigeria.
AB  - A community survey of enuresis was carried out in November/December 2002 among
      300 apparently healthy children aged 5-16 years selected systematically from the
      Ehor Local Government Area in Edo State, Nigeria. This was done with the aim of
      ascertaining the true prevalence of the disease and the contributions of some
      organic causative factors. The overall prevalence of enuresis was 21.3%. Of the
      64 children who were enuretic, 58 (91%) had only nocturnal enuresis. No strict
      daytime enuresis was recorded. Combined daytime and night time enuresis accounted
      for only six (9.4%) cases. Ninety-four percent of cases of enuresis were primary,
      while only six were secondary. Prevalence of enuresis declined significantly with
      increasing age (chi2= 14 .93, df= 3; p = 002). There was a strong association
      between enuresis and family history of bed wetting (more so with siblings) (chi2
      = 45.09, p < 0.000). Though not statistically significant, enuresis was more
      common in males, in children drawn from families of poor socio-economic status,
      among first order births, and among those with asymptomatic bacteriuria. Also,
      there was no significant association between enuresis and hemoglobin genotype.
      Organic conditions played a minimal role in the etiology of enuresis in the study
      location, but the morbidity occurred frequently enough to warrant health
      attention. A community approach is advocated because only an insignificant
      proportion is seen in orthodox health facilities.

PMID- 16903625
TI  - Prevention of viral transmission in HD units: the value of isolation.
AB  - We have investigated the influence of isolation of patients with different viral
      serology status on the transmission of viral hepatitis among patients on
      hemodialysis (HD). Our kidney center was designed to facilitate isolation of
      infected patients and implement infection control pre-cautions. These included
      separate rooms, separate entrances and exit sites, and designated HD machines for
      patients with hepatitis B, hepatitis C, and sero-negative patients. In addition,
      universal infection control polices and procedures were implemented. These
      included proper chemical and heat disinfection of all HD machines following each
      HD session. These measures were complemented with education and training of the
      nursing staff detailing strict adherence to all infection control policies and
      procedures. All of our patients and staff were vaccinated against hepatitis B.
      Our results showed that after four years of follow-up, there was a decrease in
      the annual incidence of hepatitis C seroconversion from an average of 2.4% to
      0.2%. The current prevalence of hepatitis C is 29% compared to 57% at the start
      of the study. In addition, there have been no reported sero-conversion cases of
      hepatitis B. Furthermore, our data also confirmed that the prevalence of
      hepatitis C (as well as hepatitis B) is more frequent in HD (29%) than peritoneal
      dialysis (5%) units. Surgical procedures, blood transfusion, and frequent visits
      to different dialysis units remain the major risk factors for contracting viral
      hepatitis. In conclusion, these results clearly show that isolation of patients
      and machines, together with strict adherence to infection control policies and
      procedures, result in a significant decline in the incidence and prevalence and
      better control of viral hepatitis transmission among HD patients.

PMID- 16903626
TI  - Infection and cancer following renal transplantation.
AB  - Ever increasingly potent but non-specific immunosuppression has necessarily
      brought with it the continuing risk of opportunistic infections and virus-induced
      malignancies. The improvement in graft and patient survival rates from
      transplantation has depended to a certain extent on parallel improvements in the
      diagnosis and treatment of infectious complications. This review will highlight
      some of the current problems and progress. The risks of infection are largely
      related to the total burden of immunosuppression rather than any particular drug,
      although sirolimus and the anti CD25 antibodies may be an exception. Almost all
      the post-transplant infections are treatable; a precise microbiological diagnosis
      is essential so that specific therapy can be used. Newer molecular diagnostic
      techniques are increasingly widely available, e.g.quantitative polymerase chain
      reaction. The transplant community will inevitably be faced with highly resistant
      bacteria such as. Methicillin resistant Staphylococcus Aureus (MRSA) and will
      have to develop appropriate strategies. New infectious organisms continue to be
      identified [e.g. Burkitt's Virus (BKV), West Nile virus and Avian influenza) and
      will continue to tax the ingenuity of transplant physicians and microbiologists.

PMID- 16903627
TI  - Idiopathic reversible renal failure in a young woman with minimal change
      glomerulonephritis.
AB  - We report a 19-year-old Saudi female with nephrotic syndrome whose renal biopsy
      revealed findings suggestive of minimal change glomerulonephritis (MCGN). She
      developed oliguric renal failure requiring hemodialysis. She remained dialysis
      dependent for five weeks and subsequently renal function recovered fully. She
      remained nephrotic and responded to a six week course of corticosteroids. She was
      followed for two years during which she had two relapses, which responded to
      steroids. Acute renal failure is uncommon in MCGN and is due to acute tubular
      necrosis induced by hypovolemia or drugs. This patient did not have any obvious
      precipitating factor, which led to acute reversible renal failure.

PMID- 16903628
TI  - Polyoma virus nephropathy, first reported case in Saudi Arabia.
AB  - Polyoma virus nephropathy (BK virus) is being recognized as an important cause of
      graft failure. It is usually confused with acute rejection. No cases have been
      reported from the kingdom of Saudi Arabia. We report a case of a Saudi gentleman,
      who was transplanted outside the country, with persistently elevated creatinine
      and urethral stenosis. He was treated for acute rejection on more than one
      occasion with no significant improvement in his renal function. Polyoma virus
      nephropathy was diagnosed by detecting the virus DNA by the Poly chain reaction
      technique (PCR). The patient's renal function stabilized after the calcineurin
      inhibitors were discontinued.

PMID- 16903629
TI  - Acute renal infarction secondary to atrial fibrillation - mimicking renal stone
      picture.
AB  - Acute renal infarction presents in a similar clinical picture to that of a renal
      stone. We report a 55-year-old Saudi female, known to have atrial fibrillation
      secondary to mitral stenosis due to rheumatic heart disease. She presented with a
      two day history of right flank pain that was treated initially as a renal stone.
      Further investigations confirmed her as a case of renal infarction. Renal
      infarction is under-diagnosed because the similarity of its presentation to renal
      stone. Renal infarction should be considered in the differential diagnosis of
      loin pain, particularly in a patient with atrial fibrillation.

PMID- 16903630
TI  - Primary tuberculosis of the glans penis in male kidney transplant recipients: a
      report on two cases.
AB  - An extremely rare form of genitourinary tract tuberculosis (TB) is TB of the
      glans penis. Here, we report on two men with TB of the glans, both occurring
      secondary to their wives having genital TB. To the best of our knowledge, this is
      the first report of this nature from Iran. One case is a 48 year-old blind male
      with an asymptomatic papulo-pustular eruption over the glans and, the other is a
      51 year-old male who had kidney transplantation in March 2004, and was referred
      to our transplantation clinic nine months later with papulonecrotic ulcer on the
      glans which did not respond to antibiotic therapy. Both patients responded well
      to anti-TB treatment. Our cases suggest that every papulonecrotic lesion on the
      glans must raise the suspicion of TB, and an underlying active or healed focus of
      TB should be thoroughly searched. Also, it is very important, particularly in
      endemic areas, that prior to transplanting a male patient, his female partner
      must be examined for TB of the genitalia.

PMID- 16903631
TI  - Reversible renal failure in hypertensive idiopathic nephrotics treated with
      captopril.
AB  - Angiotensin converting enzyme inhibitor (ACEI)- induced acute renal failure (ARF)
      is not as commonly reported in children as in adults. We report two cases of
      idiopathic nephrotic syndrome that developed ARF following captopril (an ACEI)
      treatment for prednisolone-induced hypertension. The two cases further alert us
      to the potential risk of ACEI-induced ARF in any nephrotic child on ACEI
      treatment. Low or high dose ACEIs should be given with extreme caution in active
      nephrotics in view of their relative hypovolemic state that may provoke ARF. The
      nephrotic children, who must be treated with ACEIs with or without diuretics,
      should be closely monitored for the development of ARF during the use of ACEIs.

PMID- 16903632
TI  - Attitude of transplant centers in the Middle East towards the follow-up of renal
      allograft live donors.
AB  - In an attempt to survey the attitude of the heads of some distinguished
      transplant programs in the Middle East countries towards the follow-up and
      complications that may ensue in the live renal allograft donors, we sent a
      questionnaire to 29 active renal transplant centers in the Kingdom of Saud Arabia
      (KSA) and some other Middle East countries, which together perform about 1500
      living renal transplantations annually. The study was performed during November
      December, 2005. Th questionnaire was intended to evaluate the presence of a
      protocol that guides the physicians in their selection, work-up and follow-up of
      the live renal allograft donors, the presence of regular time schedule for follow
      up of the donors during the first year and thereafter, and the tests performed
      during these clinic visits, the physicians' perception towards the life-long
      health insurance of the live donors as well as the physicians' estimates of the
      major complications that may occur in the live donors such a hypertension,
      proteinuria, chronic renal failure, early surgical complications and depression.
      There were 20 responses (69%) from transplant centers that together perform about
      1200 (80%) living rena transplantations annually. There were 18 (90%) respondents
      who had a protocol to guide the selection o the live renal allograft donors, 10
      (52.6%) had a written policy for post-donation follow-up of live renal allograft
      donors, 15 (83.3%) would see the donors for the first time within three months
      post-discharge, 10 (66.7%) would see the donors every three months thereafter
      during the first year and 11 (68.8%) would see them once a year after the first
      year. There was a consensus among the respondents to monitor the renal function
      tests that include plasma urea creatinine and urinalysis. The post donation
      incidence of hypertension, proteinuria, chronic renal failure, early surgical
      complications and psychological problems such as depression was estimated by more
      than 80% of the respondents as 1-5%. We conclud that the current practices
      concerning the follow-up of renal allograft live donors by the dialysis centers i
      the Middle East seem promising. However, this being a questionnaire survey,
      results may not be totall accurate. Prospective studies are required to ensure
      that protocols for follow-up are abided by.

PMID- 16903633
TI  - The problem of unintended anticoagulation in hemodialyis patients.

PMID- 16903634
TI  - Emergency hemodialysis through arterial accesses: a potential controversy.

PMID- 16903635
TI  - Should all dialysis patients be screened and treated for Helicobacter pylori
      preemptively before renal transplant?

PMID- 16903636
TI  - In response to Doctor's Diary article.

PMID- 16903637
TI  - Review of thrombotic microangiopathy (TMA), and post-renal transplant TMA.
AB  - Thrombotic microangiopathy (TMA) is a rare but devastating disorder; it involves
      small vessels and is characterized by intravascular thrombi of aggregated
      platelets leading to thrombocytopenia and variable degrees of organ ischemia and
      anemia, which is due to erythrocyte fragmentation in microcirculation. Childhood
      cases with predominant renal involvement are referred as the hemolytic uremic
      syndrome (HUS), and adults with major central neurological involvement are
      labeled as thrombotic thrombocytopenia purpura (TTP). Endothelial damage due to
      toxins and/or lack of defense against complement activation have a central role.
      Recent discovery of the von Willebrand Factor cleaving protease (ADAMTS 13) has
      offered new insight into the pathogenesis of TMA. TMA is also a well-recognized
      serious complication of renal transplantation. Clinical features of intravascular
      hemolysis are not always found. It may occur as de novo or recurrent and the
      majority of de novo cases are related to cyclosporin therapy. Viral infections,
      severe renal ischemia and acute vascular rejection are less frequent causes.
      Recurrence is negligible in diarrhea-associated HUS in childhood, but non
      diarrheal HUS recurs in majority of adults following renal transplantation. Renal
      transplantation is contraindicated in familial/relapsing recurrent forms of HUS.

PMID- 16903638
TI  - Brain death cases reported, medically documented, families approached, consented
      for donation and harvested from different hospitals in Saudi Arabia in 2005.

PMID- 16903639
TI  - Greedy doctors.

PMID- 16903640
TI  - Prolonged unconsciousness in a patient with End-stage Renal Disease.
AB  - Patients with End-stage Renal Disease being immunocompromised; are prone to a
      variety of infections, sometimes, rare ones, more than the general population.
      This fact should alert the physicians to be more vigilant and have a broader
      scope when considering the etiology of infections in such patients. We report the
      case of a 65-year-old man who had a very stormy hospital stay secondary to
      cerebral nocardiosis with multiple brain abscesses, prolonged unconsciousness and
      neurological deficits. However, the patient was treated successfully, surgically
      and chemotherapeutically. He was discharged home in a good condition.

PMID- 16903641
TI  - QT dispersions: fact or fiction?

PMID- 16903642
TI  - Role of shortened QTc dispersion in in-hospital cardiac events in patients
      undergoing percutaneous coronary intervention for acute coronary syndrome.
AB  - BACKGROUND: QT dispersion (QTD) refers to the difference between maximal and
      minimal QT values on the electrocardiogram (ECG). QTD values are calculated and
      corrected with Bazett's formula (corrected QTD = QTcD = QTD/square root of RR).
      QTcD increases in patients with acute coronary syndrome (ACS). Recovery of
      increased QTcD (shortened QTcD) develops after successful revascularization, but
      prolonged QTcD occurs in certain patients. The aim of this study is to ascertain
      the clinical significance between shortened and prolonged QTcD groups after
      percutaneous coronary intervention (PCI). METHODS: We retrospectively enrolled
      128 patients with ACS who had received PCI. The values of QTcD were measured
      manually on 12-lead standard ECGs obtained within 3 days before and after PCI
      (pre-PCI QTcD and post-PCI QTcD). All the patients were divided into 2 groups.
      The shortened QTcD group was defined as those patients with a decrease in QTcD
      after PCI and the prolonged QTcD group as those with an increase in QTcD after
      PCI. The underlying diseases, various clinical classifications and some
      prognostic factors were taken into comparison and statistical analysis between
      these 2 groups. RESULTS: The shortened QTcD group showed a significantly higher
      rate of in-hospital cardiac death (13% vs. 0%, p = 0.006) and a greater pre-PCI
      QTcD (100.8 +/- 39.5 vs. 61.3 +/- 24.1 ms, p < 0.001) than the prolonged QTcD
      group. There was a significantly greater pre-PCI QTcD in patients with cardiac
      death than those without cardiac death (111.6 +/- 38.3 vs. 83.3 +/- 38.3ms, p =
      0.027). Furthermore, the patients with in-hospital cardiac death presented with a
      significantly more frequent occurrence of in-hospital ventricular arrhythmia,
      compared with those without cardiac death (30.0% vs. 4.0%, p = 0.014).
      CONCLUSION: Among the patients with ACS undergoing PCI, directly divided into
      shortened and prolonged QTcD groups regardless of initial pre-PCI QTcD, the
      shortened QTcD group showed a higher occurrence of in-hospital cardiac death and
      a greater pre-PCI QTcD. Shortened QTcD might be 1 risk factor for in-hospital
      cardiac death.

PMID- 16903643
TI  - Sequential therapy with capecitabine followed by vinorelbine/cisplatin in
      patients with anthracycline/taxane-refractory metastatic breast cancer.
AB  - BACKGROUND: Currently, there is no standard treatment for patients with
      anthracycline and taxane-refractory metastatic breast cancer (MBC). Capecitabine
      or vinorelbine plus cisplatin is an effective palliative regimen for taxane
      refractory MBC. In this study, we analyzed the efficacy and toxicity of
      sequential therapy with capecitabine followed by biweekly vinorelbine plus
      cisplatin in 37 patients with anthracycline and taxane-refractory MBC in Taipei
      Veterans General Hospital. METHODS: Capecitabine (2,500 mg/m2 twice daily for 2
      weeks, followed by 1 week of rest) was repeated every 3 weeks until the disease
      progressed. Patients then received biweekly vinorelbine (25 mg/m2) plus cisplatin
      (40 mg/m2) (arm A, n = 17) or best supportive care (BSC) (arm B, n = 20) in
      accordance with patient preference and clinical judgment. The clinical variables
      and response to capecitabine were well balanced in both arms. RESULTS: The
      overall response rate to capecitabine was 32%, with a complete response rate of
      5% and a partial response rate of 27%. Stable disease was achieved in an
      additional 46%. The disease control rate with capecitabine was 78%. Median
      progression-free survival and overall survival with capecitabine were 5.9 and 9.5
      months, respectively. There was a trend toward better overall survival in arm A
      patients compared with arm B (BSC) patients, though statistical significance was
      not reached (10.4 vs. 7.4 months; p = 0.08); however, a significantly better
      overall survival rate was observed in the subgroup with capecitabine-controlled
      disease (10.8 vs. 6.9 months; p = 0.015). The safety profile of
      vinorelbine/cisplatin was acceptable: only 6% developed grade 4 neutropenia.
      CONCLUSION: We suggest that sequential therapy is not necessarily effective
      compared with capecitabine alone, but is probably effective in patients initially
      controllable with capecitabine.

PMID- 16903644
TI  - Role of CT and endovascular embolization in managing pseudoaneurysms of the
      internal maxillary artery.
AB  - BACKGROUND: The purpose of this study was to evaluate the role of computed
      tomography (CT) and endovascular embolization in managing 10 patients with 11
      internal maxillary arterial pseudoaneurysms (IMPAs) with acute oronasal
      hemorrhage. METHODS: A series of 10 patients with 11 IMPAs presenting with
      profuse oronasal hemorrhage, all treated with endovascular embolization, were
      reviewed. There were 9 males and 1 female ranging in age from 10 to 56 years
      (mean, 38 years). The predisposing factors of IMPA were trauma (n = 6) or head
      and neck carcinomas (HNCs) after surgical treatment and/ or postradiation therapy
      (n = 5). Before embolization, all patients had CT of maxillofacial regions to
      evaluate the extension of trauma or to evaluate the treatment outcome for HNCs.
      Endovascular embolization was employed-to occlude the IMPAs by delivering the
      embolic agents of liquid adhesives (n = 9) or microcoils (n = 2) to the IMPAs.
      RESULTS: On the lesion side, CT revealed maxillofacial fractures in all 5 trauma
      patients and recurrent or residual tumors in 3 patients with HNCs. In the other 2
      patients with HNCs, CT showed no significant finding and contributed little to
      the catheter angiography in detecting the IMPAs. Endovascular treatment was
      technically successful in all 11 IMPAs, ceasing hemorrhage immediately after
      embolization. No recurrence of bleeding was observed. No patient developed
      neurologic deficit, skin, or mucosal necrosis at the maxillofacial region.
      Clinical follow-up was 2-36 months (mean, 14 months). Two patients with advanced
      carcinoma died during follow-up because of disease progression. CONCLUSION: CT is
      a useful tool for guiding catheter angiography to localize the majority of IMPAs.
      Endovascular embolization can succeed in managing IMPAs, and should be performed
      as soon as the IMPA is depicted.

PMID- 16903645
TI  - Esophageal atresia with tracheoesophageal fistula: ten years of experience in an
      institute.
AB  - BACKGROUND: Esophageal atresia (EA), tracheoesophageal fistula (TEF), or both is
      a complicated problem. The purpose of this study was to evaluate the outcomes and
      postoperative complications in patients with EA/TEF who were admitted to our
      hospital. METHODS: In total, 15 patients were enrolled from 1994 to 2003,
      including 8 males and 7 females. Patient demographics, associated anomalies, and
      outcomes were analyzed. RESULTS: The most common variant was EA with a distal TEF
      (type C), which occurred in 12 patients (80%). The latter had associated
      congenital anomalies, and cardiac anomalies were the most frequent, occurring in
      8 patients (53.3%). Of the 6 cases who had life-threatening anomalies, 4 (66.7%)
      died, and of the 9 cases who had no life-threatening-anomalies, 2 (22.2%) died.
      Tracheomalacia and/or stenosis were diagnosed in 8 patients (66.7%)
      postoperatively. Though 3 of the 4 cases who suffered from dying spell received
      intratracheal stent implantation, 2 cases still died. CONCLUSION: The survival
      rate of the patients with EA/TEF is influenced mainly by associated life
      threatening anomalies. TMS combined with a history of dying spell may be the
      major fatal complication.

PMID- 16903646
TI  - Salivary gland carcinoma of the larynx.
AB  - BACKGROUND: Salivary gland carcinomas of the larynx are rare, and account for <
      1% of laryngeal malignancy. The purpose of this study is to review our management
      experience of salivary gland carcinomas of the larynx in Taipei Veterans General
      Hospital and to compare it with other major existing series. METHODS: From 1981
      to 2000, 11 patients with laryngeal salivary gland carcinomas treated in Taipei
      Veterans General Hospital were included in this study. Their demographic data,
      treatment modalities, survival, and failure pattern, obtained by review of
      medical records, were analyzed. RESULTS: All 11 patients were male. Median follow
      up period was 95 months (range, 18-181 months). The 5-year overall survival rate
      of all patients was 71%, and the 5-year disease-specific survival rate was 83%.
      CONCLUSION: The mainstay treatment of laryngeal salivary gland carcinomas in
      these cases was surgery or surgery with postoperative radiotherapy. The survival
      rate was satisfactory and similar to that of squamous cell carcinoma of the
      larynx.

PMID- 16903647
TI  - Abdominal aortic dissection with acute mesenteric ischemia in a patient with
      Marfan syndrome.
AB  - Marfan syndrome is an autosomal dominant inherited disorder of connective tissue,
      with various complications manifested primarily in the cardiovascular system. It
      potentially leads to aortic dissection and rupture, these being the major causes
      of death. We report a patient who complained of acute abdominal pain, which
      presented as acute mesenteric ischemia combined with abdominal aortic dissection.
      Echocardiography showed enlargement of the aortic root and mitral valve prolapse.
      Abdominal computed tomography scan revealed acute mesenteric ischemia due to
      abdominal aortic dissection. Finally, the patient underwent surgery of aortic
      root replacement and had a successful outcome. Therefore, we suggest that for
      optimal risk assessment and monitoring of patients with Marfan syndrome, both
      aortic stiffness and the diameter of the superior mesenteric vein compared with
      that of the superior mesenteric artery are useful screening methods to detect
      acute mesenteric ischemia secondary to abdominal aortic dissection. Early
      diagnosis and early treatment can decrease the high mortality rate of patients
      with Marfan syndrome.

PMID- 16903648
TI  - Idiopathic acute eosinophilic pneumonia.
AB  - Idiopathic acute eosinophilic pneumonia (IAEP) is a rare disease but of clinical
      importance because of its good prognosis if treated promptly and appropriately.
      The etiology remains unknown and the temporal relationship between IAEP and a
      history of resent onset of cigarette smoking has been described. We report a
      typical case of a 21-year-old male with recent onset of smoking, who presented
      with acute febrile hypoxemic respiratory failure. High-resolution chest computed
      tomography scan revealed patchy ground glass opacity and ill-defined nodules,
      diffuse interlobar and interlobular septal thickening, and bilateral small amount
      of pleural effusion, which mimicked congestive heart failure except that the
      heart size was within normal limits. Bronchoalveolar lavage (BAL) was performed
      soon after the patient was admitted and remarkable eosinophilia was noted in BAL
      fluid. Clinical condition and chest radiographs improved dramatically after
      corticosteroid treatment. Because effective treatment and prompt institution of
      therapy can obviate unnecessary morbidity and mortality, IAEP should be kept in
      mind when treating patients presenting with diffuse parenchymal lung disease and
      acute respiratory failure. In that case, BAL is valuable and should be performed
      as soon as possible.

PMID- 16903649
TI  - Primary malignant melanoma of the esophagus.
AB  - Primary malignant melanoma of the esophagus is an uncommon but aggressive tumor
      with fatal prognosis. We present 2 male patients with a history of dysphagia for
      a period of time and describe the imaging features of esophagograms and chest
      computed tomography (CT) scan. Both were proved by endoscopic biopsy. One of them
      underwent surgical resection. Primary malignant melanomas of the esophagus should
      be included in the differential diagnosis of bulky and polypoid masses that
      expand the esophagus without causing obstruction on esophagograms and chest CT
      scan.

PMID- 16903650
TI  - Assessment with magnetic resonance imaging and spectroscopy in Lhermitte-Duclos
      disease.
AB  - Lhermitte-Duclos disease (LDD) is a rare benign lesion of uncertain pathogenesis
      characterized by distortion of the normal cerebellar laminar cytoarchitecture. We
      report a 22-year-old man admitted for injury sustained in a traffic accident with
      the incidental finding of a cerebellar mass. Magnetic resonance imaging (MRI)
      revealed a mass lesion within the right cerebellar hemisphere. The final
      diagnosis of LDD was made by obtaining a surgical specimen and identifying the
      characteristic appearance of the lesion by MRI study. The images showed the
      typical striated pattern of hyperintensity on T2-weighted images and
      corresponding hypointensity on T1-weighted images, as well as the typical absence
      of enhancement following gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA)
      administration. In addition, no disturbance of water diffusion on diffusion
      weighted MRI, and associations of decreases in the N-acetylaspartate/creatine
      (NAA/Cr) and NAA/Choline (Cho) ratios with near normal values of Cho/Cr, as well
      as an obvious lactate peak gave supplemental information for diagnosis.

PMID- 16903651
TI  - HIT interoperability: good intentions must lead to tangible results.

PMID- 16903652
TI  - IT tools personalize healthcare marketing and communications.

PMID- 16903653
TI  - HHS moves forward with E-prescribing standards.

PMID- 16903654
TI  - Transforming IT--aligning to healthcare business drivers.

PMID- 16903655
TI  - The new alphabet soup: models of application integration.

PMID- 16903656
TI  - Creating a seamless IT enterprise: the rest of the story.

PMID- 16903657
TI  - The holy grail: cost-effective healthcare evidence transparently and consistently
      used by clinicians.

PMID- 16903658
TI  - The perfect storm for electronic health records.
AB  - EHRs and data sharing improve quality, reduce costs, and enhance workflow. They
      create a c ommunity of clinical collaboration, fostering the adoption of new
      knowledge and best practices. With government, provider, and payer support for
      the nationwide rollout of electronic records, 2006 will be the year in which the
      United States makes significant progress on the journey to deliver electronic
      systems to all clinicians.

PMID- 16903659
TI  - Building an interoperable regional health information network today with IHE
      integration profiles.
AB  - One of the key challenges of architecting electronic record sharing solutions
      that are scalable and can provide acceptable performance is how to create a
      longitudinal record for a patient when the desired data will be stored in several
      distributed point-of-service systems. This paper will review the design and
      standards selection process that has been made by Integrating the Healthcare
      Enterprise, a multi-national collaborative of care providers and developers that
      analyzed a variety of approaches. In particular, the requirements, issues, and
      alternative solutions for scalable, standards-based data locating services
      supporting regional and national health information exchange solutions will be
      discussed. Guidance will be offered to architects of regional health information
      organizations to take advantage of this experience and leverage the IHE Technical
      Framework, its testing processes, and tools to accelerate their projects and
      facilitate the interfacing of EHR systems serving different care settings from
      different vendors or developers. The implementation experience in 2005-2006 of
      the IHE Integration Profile specifications supporting an interoperable RHIO
      solution among various EHR systems from more than 30 vendors will be analyzed,
      with key lessons summarized.

PMID- 16903660
TI  - RHIOs--build in healthcare fraud management from the beginning.
AB  - This article presents the Department of Health and Human Services, Office of the
      National Coordinator for Health Information Technology's field-based research on
      the use of Health Information Technology to Advance and Expand Healthcare Anti
      Fraud Activities.' The authors of this article directed and performed this
      research under contract to the Foundation of Research and Education of AHIMA.
      There is a tremendous potential to reduce healthcare fraud and achieve
      substantial financial benefits using a nationwide health information network with
      interoperable electronic health records. To achieve these benefits, there must be
      interoperability among providers and between providers and payers. The article
      will provide recommendations for regional health information organizations to
      incorporate healthcare fraud management in their early designs.

PMID- 16903661
TI  - Using IHE and HL7 conformance to specify consistent PACS interoperability for a
      large multi-center enterprise.
AB  - As part of its patient care mission, the U.S. Veterans Health Administration
      performs diagnostic imaging procedures at 141 medical centers and 850 outpatient
      clinics. VHA's VistA Imaging Package provides a full archival, display, and
      communications infrastructure and interfaces to radiology and other HIS modules
      as well as modalities and a worklist provider In addition, various medical center
      entities within VHA have elected to install commercial picture archiving and
      communications systems to enable image organization and interpretation. To
      evaluate interfaces between commercial PACS, the VistA hospital information
      system, and imaging modalities, VHA has built a fully constrained specification
      that is based on the Radiology Technical Framework (Rad-TF) Integrating the
      Healthcare Enterprise. The Health Level Seven normative conformance mechanism was
      applied to the IHE Rad-TF and agency requirements to arrive at a baseline set of
      message specifications. VHA provides a thorough implementation and testing
      process to promote the adoption of standards-based interoperability by all PACS
      vendors that want to interface with VistA Imaging.

PMID- 16903662
TI  - Concepts for building inter-organizational systems in healthcare: lessons from
      other industries.
AB  - A centerpiece of the nation's healthcare information technology vision is the
      implementation of health information exchanges (HIEs). HIEs have the significant
      potential to improve the quality of patient care, reduce care costs, and enhance
      patient safety. These kinds of exchanges are new to healthcare in the United
      States. While more than 200 communities are in various stages of implementing
      them, there is little mature experience with the factors that contribute to the
      successful formation and sustainability of these exchanges. The creation and
      management of mechanisms to support the exchange of data between organizations
      has been used in other industries. There are many examples of interorganizational
      systems that have been established in industries as diverse as banking,
      manufacturing, government, and retail. This paper examines some of these
      experiences and attempts to glean the concepts and guidance healthcare can learn
      from other industries.

PMID- 16903663
TI  - A tale of three cities--where RHIOS meet the NHIN.
AB  - Regional health information exchanges in California, Indiana, and Massachusetts
      have been collaborating on a prototype for a nationwide health information
      network, first under the auspices of the Markle Foundation's Connecting for
      Health program and now under contract to the Department of Health and Human
      Services' Office of the National Coordinator for Health Information Technology.
      Since mid-2004, this collaboration has evolved from a collection of regional
      efforts to a standards-driven cooperative and now to one of four prototype
      national networks fostered by federal efforts. This development reflects a
      maturing market for interoperability and integration in healthcare information
      technology, starting with RHIOs, and suggests one response to the industry's need
      for the type of plug-and-play information exchange available in other industries.
      The authors share their experiences and their views of how RHIOs and a Nationwide
      Health Information Network will further develop to make interoperable electronic
      health records a reality in coming years. The content of this article is solely
      the responsibility of the authors and does not necessarily represent the official
      view of the Office of the National Coordinator for Health Information Technology.

PMID- 16903664
TI  - The California Clinical Data Project: a case study in the adoption of clinical
      data standards for quality improvement.
AB  - The California Clinical Data Project is a statewide initiative to remove barriers
      to the widespread and effective use of information technology to improve chronic
      disease care. The project is a case study in the development and widespread
      adoption of clinical data standards by varied and often competing stakeholders.
      As an initial step, the project defined precise data standards for the batch
      reporting of pharmacy claims data and laboratory results data. These uniform
      standards facilitate the flow of existing electronic clinical information into
      disease registries and electronic health record systems. Pharmacy and lab results
      data now are being exchanged electronically with this standard among the largest
      health plans, medical groups, and clinical laboratories participating in
      California's pay-for-performance programs. Lessons from this project may apply to
      the development and adoption of data standards for other states and locales and
      for the emerging national health information infrastructure.

PMID- 16903665
TI  - EHR and other IT adoption among physicians: results of a large-scale statewide
      analysis.
AB  - Despite a national push toward the adoption of health information technologies,
      much is still unknown about the use of IT in physician's offices. We surveyed all
      primary care physicians and a 25 percent stratified random sample of other
      specialists (total n=14,921) in Florida to better understand current trends and
      factors related to the use of IT in the ambulatory setting. Data was analyzed
      using logistic regression modeling techniques to compute adjusted odds ratios.
      Covariates included practice size, medical training, practice type, age, race,
      and gender Routine office computer use (80 percent) was found to be very common
      for administrative functions. The use of quality enhancing technologies such as
      PDAs (37.5 percent), use of e-mail with patients (16.6 percent) and EHR (23.7
      percent) was less common. Overall, large practice size, specialty practice,
      physician age and gender, and multi-specialty practice affiliation were
      significantly related to the use of many, but not all, of these IT applications
      in the ambulatory setting.

PMID- 16903666
TI  - Use of the Omaha System data to validate Medicare required outcomes in home care.
AB  - Millions of dollars have been spent developing standardized terminologies for
      nursing. However, many nurses are unaware of them, because vendors have not
      incorporated them into electronic health records (EHRs), and quality assurance
      staff and researchers have not benefited from reuse of the data to examine
      practice. Government regulations require the use of particular data sets, such as
      OASIS in home care. Most staff and agencies are focused on government-mandated
      data without realizing how the nationally recognized terminologies for nursing
      can benefit an agency. This article seeks to demonstrate the value of using the
      Omaha System in an EHR for documenting care and conducting Medicare's required
      Outcome-Based Quality Improvement process in one home care agency.

PMID- 16903667
TI  - Polyhydroxyalkanoate (PHA)/inorganic phase composites for tissue engineering
      applications.
AB  - Polyhydroxyalkanoates are emerging as a class of biodegradable polymers for
      applications in tissue engineering. Members of the polyhydroxyalkanoates family
      encompass a wide variety of materials, from hard and brittle materials to soft
      and elastomeric. Over the years, efforts have been made to extend the group of
      polyhydroxyalkanoates and to investigate their use in numerous biomedical
      applications, such as sutures, cardiovascular patches, wound dressings, guided
      tissue repair/regeneration devices, and tissue engineering scaffolds. Along with
      the development of polyhydroxyalkanoates, researchers have looked into the
      possibility of designing composites in combination with inorganic phases to
      further improve the mechanical properties, rate of degradation, and also impart
      bioactivity. Poly(3-hydroxybutyrate), poly(3-hydroxybutyrate-co-3
      hydroxyvalerate), and poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) are some of
      the polymers which have been studied extensively to fabricate composites in
      combination with hydroxyapatite, bioactive glass, and glass-ceramic fillers or
      coatings. This paper reviews international research carried out toward
      development of polyhydroxyalkanoates/inorganic phase composites in terms of
      systems investigated, microstructures, properties achieved, and applications,
      with special focus on tissue engineering scaffolds. A comparison between
      different composite systems developed in the past few years is presented. The
      paper also addresses the prospect of potential further development of
      polyhydroxyalkanoates/inorganic phase composites with optimized microstructure
      and properties for improved tissue engineering scaffolds.

PMID- 16903668
TI  - Full-length single-walled carbon nanotubes decorated with streptavidin-conjugated
      quantum dots as multivalent intracellular fluorescent nanoprobes.
AB  - We report the formation of a supramolecular luminescent nanoassembly composed of
      individual or small ropes of full-length, single-walled carbon nanotubes
      decorated with streptavidin-conjugated quantum dots. The supramolecular
      luminescent nanoassembly was stably dispersed under physiological conditions and
      was readily visible by both optical and confocal fluorescent microscopies. Jurkat
      T leukemia cells were able to internalize the nanoassembly by multivalent CD3
      receptor-mediated endocytosis (adsorption by cell). Once internalized by cells,
      the nanoassembly was found to be transported to lysosomes. These properties
      should make this supramolecular luminescent nanoassembly an excellent building
      block for the construction of intracellular polyvalent nanoprobes, mimicking
      natural viral delivery entities with enhanced loading capacity compared to small
      molecules.

PMID- 16903669
TI  - Quantal self-assembly of polymer layers in polypeptide multilayer nanofilms.
AB  - Simple molecular models predict key aspects of the "microscopic" assembly
      behavior of various peptide systems in the fabrication of multilayer films. Such
      films show substantial differences in density for different peptide systems. The
      data suggest that exponential film growth is possible in the absence of polymer
      diffusion and that "macroscopic" assembly behavior is more a function of peptide
      peptide interactions than peptide sequence alone.

PMID- 16903670
TI  - Enzymatic synthesis and characterization of novel biodegradable copolymers of 5
      benzyloxy-trimethylene carbonate with 1,4-dioxan-2-one.
AB  - Enzymatic ring-opening copolymerization of 5-benzyloxy-trimethylene carbonate
      (BTMC) and 1,4-dioxan-2-one (DON) was investigated for the first time.
      Immobilized porcine pancreas lipase (IPPL) on silica particles was selected to
      perform the copolymerization. A series of novel biodegradable copolymers with
      different compositions were characterized by (1)H NMR, (13)C NMR, and GPC. The
      influences of reaction conditions such as polymerization time and catalyst
      concentration on the yield and molecular weight of the copolymers were also
      studied. The copolymerizations of different monomer feed ratios were carried out
      in bulk at 150 degrees C with 4.5 wt per thousand IPPL as a catalyst for 24 h.
      With the increase of the BTMC molar feed ratio from 20% to 79%, the M(n) of the
      resulting copolymers increased from 5600 to 63400. Water uptake and static
      contact angle experiments showed that the hydrophilicity of copolymers could be
      improved with increasing DON content in the copolymers. Moreover, the in vitro
      drug release rate (ibuprofen as the model drug) of the resulting copolymers also
      increased along with the DON content in the copolymers.

PMID- 16903671
TI  - Carbosilane dendrimers bearing globotriaoses: syntheses of globotrioasyl
      derivative and introduction into carbosilane dendrimers.
AB  - As an application of a one-pot reaction involving Birch reduction and subsequent
      S(N)2 reaction in liquid ammonia, synthetic assembly of trisaccharidic moieties
      of globotriaosyl ceramide onto carbosilane dendrimers was accomplished using
      tris(3-bromopropyl)phenylsilane and tris[tris(3
      bromopropyl)silylpropyl]phenylsilane as the core scaffolds. The common
      globotriaosyl derivative having benzylsulfide functionality at the terminal of
      the aglycon was efficiently prepared from d-galactose and d-lactose as starting
      materials. The glycosyl donor derived from galactose and the glycosyl acceptor
      derived from lactose were condensed in the presence of silver triflate as the
      best promoter to provide corresponding trisaccharide with newly formed alpha-1-4
      linkages in 90% yield. Fully benzylated protection of the trisaccharide was
      deprotected under the Birch reduction condition followed by acetylation to give
      an acetate in which alkene was converted into benzyl sulfide by radical addition
      of alpha-toluenethiol in high yields. On the other hand, carbosilane dendrimers
      were prepared from appropriate chlorosilanes as starting materials by a
      combination of hydrosylation followed by alkenylation. The terminal C=C double
      bonds of the carbosilanes were converted into corresponding alcohols by means of
      the usual hydroboration reaction, and the alcohols underwent further chemical
      manipulation to give carbosilane dendrimers with peripheral bromine atoms.

PMID- 16903672
TI  - Carbosilane dendrimers bearing globotriaoses: construction of a series of
      carbosilane dendrimers bearing globotriaoses.
AB  - To enhance biological activities on the basis of the sugar cluster effect, a
      series of carbosilane dendrimers as core scaffolds for the construction of
      glycodendrimers was systematically synthesized from appropriate chlorosilanes by
      a combination of alkenylation and hydrosylation reactions. Those carbosilane
      dendrimers having terminal C=C double bonds underwent general hydroboration
      reactions to give corresponding primary polyols. Further transformations of the
      alcohols were then performed by mesylation followed by a displacement with NaBr
      to provide corresponding dendrimers with 4 to 36 bromine atoms at each terminal
      end. Assembly of trisaccharide moieties of globotriaosyl ceramide using alkyl
      halide-type carbosilane dendrimers as the core frame was conducted in liquid
      ammonia by a one-pot reaction involving selective removal of a benzyl group under
      the Birch reduction condition and subsequent S(N)2 reaction to yield a series of
      carbosilane dendrimers having appropriate numbers of trisaccharide moieties.
      These dendrimers have unique shapes and adequate numbers of terminal
      trisaccharide moieties. Some of the dendrimers showed unique biological activity
      against Stxs, which were produced by pathogenic Escherichia coli O157:H7.

PMID- 16903673
TI  - Polyolefin matrixes with permanent antibacterial activity: preparation,
      antibacterial activity, and action mode of the active species.
AB  - Poly[2-(tert-butylamino)ethyl methacrylate] (PTBAEMA) belongs to a novel class of
      water-insoluble biocides. Dispersion of a poly(ethylene-co-butylene)-b-poly[2
      (tert-butylamino)ethyl methacrylate] diblock copolymer (PEB-b-PTBAEMA) within low
      density polyethylene (LDPE) imparts antimicrobial properties to the polyolefin as
      assessed by the viable cell counting method against Escherichia coli (E. coli).
      This diblock copolymer has been synthesized by atom transfer radical
      polymerization (ATRP) with a poly(ethylene-co-butylene) (PEB) oligomer end-capped
      by an activated bromide as a macroinitiator for the polymerization of 2-(tert
      butylamino)ethyl methacrylate (TBAEMA). Morphological changes of E. coli bacteria
      in contact with modified LDPE have been observed by transmission and scanning
      electron microscopy and indicate that the diblock copolymer is bactericide rather
      than bacteriostatic. Finally, the action mode of the PEB-b-PTBAEMA copolymer more
      likely relies on the displacement of the Ca(2+) and/or Mg(2+) ions of the outer
      membrane of the bacteria, which is disorganized and finally disrupted.

PMID- 16903674
TI  - Biotinylated glycopolymers synthesized by atom transfer radical polymerization.
AB  - Biotinylated glycopolymers that bind to the protein streptavidin were synthesized
      by atom transfer radical polymerization (ATRP). Poly(methacrylate)s with pendent
      N-acetyl-d-glucosamines were prepared by polymerizing the protected monomer,
      followed by deprotection. Alternatively, the unprotected monomer was directly
      polymerized. Both paths provided well-defined glycopolymers with narrow molecular
      weight distributions (PDI = 1.07-1.23). The number-average molecular weights
      determined by gel permeation chromatography increased with increasing initial
      monomer-to-initiator ratios. The polymers were synthesized using a biotin
      functionalized initiator for ATRP. Confirmation of the end group and binding to
      the protein streptavidin was achieved by (1)H NMR and surface plamon resonance.

PMID- 16903675
TI  - Gamma-radiation induced changes in the physical and chemical properties of
      lignocellulose.
AB  - gamma-radiation induced effects on the physical and chemical properties of
      natural lignocellulose (jute) polymer were investigated. Samples were irradiated
      to required total doses at a particular dose rate. The changes in the parameters
      such as the tensile strength, elongation at break, and work done at rupture for
      the lignocellulose samples on irradiation with the gamma-rays from a cobalt-60
      source were measured. The mechanical properties were found to have nonlinear
      relations with the radiation doses. The chemical stability of irradiated fibers
      was found to degrade progressively with the increase of radiation dose.
      Additionally, other chemical changes of the samples due to exposure to high
      energy radiation were also investigated using fluorescence and infrared
      spectroscopic analysis. Differential scanning calorimetry and thermogravimetric
      studies showed a significant reduction in thermal stability. The wide-angle X-ray
      diffraction study showed that structural changes of cellulose appeared due to the
      radiation-induced chemical reaction of lignocellulose.

PMID- 16903676
TI  - Genotype-specific spatial distribution of starch molecules in the starch granule:
      a combined CLSM and SEM approach.
AB  - Starch granule types from a variety of botanical sources were selected to
      represent differences in crystalline polymorph, amylose and phosphate content,
      and amylopectin chain length distribution. Equimolar labeling of starch molecules
      with the fluorophore 8-amino-1,3,6-pyrenetrisulfonic acid (APTS) was used to
      construct a detailed map of the distribution of amylose and amylopectin within
      the granule by confocal laser scanning microscopy (CLSM) analysis. Medium- and
      high-resolution scanning electron microscopy (SEM) were used to provide detailed
      images of granule surface structures. By using a combined surface and internal
      imaging approach, interpretations of a number of previous structural observations
      is presented. In particular, internal images of high amylose maize and potato
      suggest that multiple initiations of new granules are responsible for the
      compound or elongated structures observed in these starches. CLSM optical
      sections of rice granules revealed an apparent altered distribution of amylose in
      relation to the proposed growth ring structure, hinting at a novel mechanism of
      starch molecule deposition. Well-described granule features, such as equatorial
      grooves, channels, cracks, and growth rings were documented and related to both
      the internal and external observations. A new method for probing the phosphate
      distribution in native granules was developed using a phosphate-binding
      fluorescent dye and CLSM.

PMID- 16903677
TI  - X-ray diffraction study into the effects of liming on the structure of collagen.
AB  - The manufacture of parchment from animal skin involves processes that remove
      hair, fats, and other macromolecules. Although it is well understood that the
      collagen fibers "open up" during processing, this study uses small and wide-angle
      X-ray diffraction to measure quantitatively the changes induced at the nanoscopic
      and microscopic levels. The axial rise per residue distance within the collagen
      molecules is unaffected by salt and lime treatments. Salting of the hides appears
      to remove noncollagenous materials. The intermolecular lateral packing distance
      between the hydrated collagen molecules (1.4 nm) increases after salting (
      approximately 1.5 nm) and liming ( approximately 1.55 nm); drying is responsible
      for a reduction to approximately 1.2 nm in all samples. The axial staggered array
      (d spacing) is reduced by 1 nm after liming and is unaffected by drying. The
      average fibril diameter increases from 103.2 to 114.5 nm following liming, and
      the fibril-to-fibril distance increases from 122.6 to 136.1 nm.

PMID- 16903678
TI  - Encapsulation of drug reservoirs in fibers by emulsion electrospinning:
      morphology characterization and preliminary release assessment.
AB  - In this paper, we prepared composite fibers via electrospinning from either W/O
      or O/W emulsion. SEM images demonstrate the beads-in-string structures in these
      fibers and proved this technique to be an effective method for
      microencapsulation. As a practical application, Ca-alginate microspheres, which
      serve as reservoirs for hydrophilic drugs, were prepared in a reverse emulsion
      and then incorporated into poly (l-lactic acid) (PLLA) fibers by electrospinning.
      With the bovine serum albumin (BSA) loaded into the microspheres, the beads-in
      string structure thus entrapped hydrophilic proteins in hydrophobic polymeric
      matrix. In the in vitro release test, BSA, which was released from composite
      fibers, achieved prolonged release profiles and lower burst release rates than
      those from naked Ca-alginate microspheres. In comparison with other well
      established techniques to prepare microcapsules, such as solvent evaporation and
      spray-drying techniques, emulsion electrospinning features partly competing,
      partly complementary characteristics. Extension to other emulsion systems will be
      able to fabricate new types of functional structures.

PMID- 16903679
TI  - Adhesion of polyelectrolyte microcapsules through biotin-streptavidin specific
      interaction.
AB  - Adhesion of PAH/PSS and PDADMAC/PSS capsules through electrostatic and specific
      interactions has been investigated using reflective interference contrast
      microscopy (RICM). Adhesion of capsules via electrostatic interactions was found
      to be spontaneous and strong. Capsules functionalized with poly(l-lysine)-graft
      poly(ethylene glycol) (PLL-g-PEG) did not exhibit significant adhesion (as
      determined by the adhesion area) to streptavidin-coated substrates, whereas
      capsules functionalized with biotinylated PLL-g-PEG showed a significantly larger
      adhesion area. Using continuum mechanical models, the total adhesion energies for
      these cases were calculated and were found to correspond to several tens of
      individual biotin-streptavidin pairs. The application of specific interactions
      such as the biotin-streptavidin system for controlled capsule adhesion has been
      demonstrated in this study.

PMID- 16903680
TI  - Solution structures of two structural isoforms of CMrVIA chi/lambda-conotoxin.
AB  - alpha-Conotoxins possess a conserved four-cysteine framework and disulfide
      linkages (C(1)(-)(3), C(2)(-)(4)) that fold toward the globular conformation with
      absolute fidelity. Despite the presence of a similar conserved set of cysteine
      framework, chi/lambda-conotoxins adopt an alternate disulfide-pairing (C(1)(
      )(4), C(2)(-)(3)) and its consequent ribbon conformation, exhibiting distinct
      biological activities from alpha-conotoxins. chi/lambda-Conotoxin CMrVIA
      (VCCGYKLCHOC-COOH) isolated from the venom of Conus marmoreus natively exists in
      the ribbon conformation and induces seizures in mice at a potency that is of
      three orders higher than the non-native globular form. We have chemically
      synthesized two isoforms of CMrVIA conotoxin in the ribbon and globular
      conformation and determined their structures by (1)H NMR spectroscopy. The ribbon
      (PDB ID 2B5P) and globular conformations (PBD ID 2B5Q) were calculated to have
      paired-wise backbone RMSDs of 0.48 +/- 0.1 and 0.58 +/- 0.1 A respectively.
      Unlike the native globular alpha-conotoxins, the globular canonical form of
      CMrVIA chi/lambda-conotoxin exhibited heterogeneity in its solution structure as
      noted by the presence of minor conformers and poorer RMSD of structure
      calculation. Paired-wise backbone comparison between the native ribbon and the
      non-native globular form of CMrVIA conotoxin revealed an RMSD of 4.73 A,
      emphasizing their distinct conformational differences. These structural data are
      essential for the understanding of the structure-function activity of chi/lambda
      conotoxins, as well as unraveling the folding propensities of these short peptide
      toxins.

PMID- 16903681
TI  - Semitelechelic HPMA copolymers functionalized with triphenylphosphonium as drug
      carriers for membrane transduction and mitochondrial localization.
AB  - Semitelechelic HPMA (N-(2-hydroxypropyl)methacrylamide) copolymers possessing a
      single terminal lipophilic triphenylphosphonium (TPP) cation and fluorescent
      labels were synthesized to determine how the attached cation affected cellular
      uptake and intracellular trafficking. In vitro mitochondrial uptake fluorescence
      quenching assays using isolated mouse liver mitochondria indicated that only
      lower molecular weight (<5 kDa) BODIPY FL-labeled TPP-semitelechelic HPMA
      copolymers exhibited significant organelle localization or uptake. In vitro
      cellular uptake and intracellular trafficking was evaluated using cultured human
      ovarian carcinoma cells. Cells incubated with all types of TPP copolymers used in
      the study appeared to internalize the polymer by endocytosis only, and all of the
      internalized copolymer was confined to the lysosomal compartment after 24 h.
      Endocytotic uptake of the TPP-HPMA copolymer conjugates was rapid, suggesting
      that they were internalized by adsorptive endocytosis, rather than fluid-phase
      pinocytosis. Low-molecular weight (<5 kDa) and high-molecular weight (>5 kDa)
      semitelechelic copolymers, microinjected into cultured cells indicated that the
      TPP moiety did not significantly localize the polymers to mitochondria.

PMID- 16903682
TI  - Removable colored coatings based on calcium alginate hydrogels.
AB  - This article describes the creation of a nontoxic, biodegradable coating using
      calcium alginate and FD&C approved dyes. The coating is robust but is rapidly
      removed upon treatment with disodium ethylenediamine tetraacetate (EDTA). Dye
      leaching from calcium alginate films was studied, and it was determined that the
      efficiency of dye retention is proportional to the degree of cross-linking.
      Degradation rates were studied on calcium alginate beads serving as a model for a
      coating. We determined that degradation rates depend on the gel's cross-linking
      and on the amount of EDTA used. Bead size also influenced the degradation rates;
      smaller beads degraded faster than larger beads. We show that the coating can be
      used as an easily removable and environmentally friendly logotype on an
      artificial turf surface. Applications of these coatings can be extended to food,
      cosmetic, medicinal, and textile uses and to wherever nontoxic, easily removable
      colored coating is desired.

PMID- 16903683
TI  - Core/Shell nanoparticles with lecithin lipid cores for protein delivery.
AB  - Core/shell nanoparticles with lipid core, were prepared and characterized as a
      sustained delivery system for protein. The lipid core is composed of protein
      loaded lecithin and the polymeric shell is composed of Pluronics (poly(ethylene
      oxide)-poly(propylene oxide)-poly(ethylene oxide) triblock copolymer, F-127).
      Based on the preparation method in the previous report by us, the freeze-drying
      of protein-loaded lecithin was performed in the F-127 aqueous solution containing
      trehalose used as a cryoprotectant to form stabilized core/shell nanoparticles.
      Cryo-TEM (transmittance electron microscopy) and a particle size analyzer were
      used to observe the formation of stabilized core/shell nanoparticles. For the
      application of core/shell nanoparticles as a protein drug carrier, lysozyme and
      vascular endothelial growth factor (VEGF) were loaded into the core/shell
      nanoparticles by electrostatic interaction, and the drug release pattern was
      observed by manipulating the polymeric shell.

PMID- 16903684
TI  - Immunostimulatory polysaccharides from Chlorella pyrenoidosa. A new
      galactofuranan. measurement of molecular weight and molecular weight dispersion
      by DOSY NMR.
AB  - Fractionation of the hot water extract of Chlorella pyrenoidosa was performed
      using a combination of ethanol precipitation, size exclusion chromatography, and
      anion exchange chromatography. One fraction contained a new polysaccharide, and
      this compound was shown to be a 1-->2-linked beta-d-galactofuranan from its 1D
      and 2D (1)H and (13)C NMR spectra, with a molecular weight of 15 kDa from DOSY
      NMR measurements. A number of other fractions were shown to have the same
      repeating unit as the previously identified arabinogalactan. However,
      arabinogalactans from different fractions were shown by DOSY NMR to have
      different molecular weights, which ranged from 27 to 1020 kDa. Agreement with
      molecular weights measured for some of these fractions by SEC-MALS was very good,
      further confirming the relationship established by Viel et al. between molecular
      weights of neutral polysaccharides and self-diffusion coefficients. The smaller
      molecular weight polysaccharides, the galactofuranan and the 27 and 50 kDa
      arabinogalactans, were shown to be close to monodisperse by analysis of the
      distributions of the self-diffusion coefficients for the polymers. The larger
      arabinogalactans had considerable variation in their molecular weights (188 +/-
      109 kDa and 1020 +/- 370 kDa). Only the two larger arabinogalactans showed
      immunostimulatory activity.

PMID- 16903685
TI  - New asymmetric AB(n)-shaped amphiphilic poly(ethylene glycol)-b-[poly(l
      lactide)](n) (n = 2, 4, 8) bridged with dendritic ester linkages: I. Syntheses
      and their characterization.
AB  - This study presents new investigations on chemical syntheses and characterization
      of new asymmetric AB(n)-shaped amphiphilic diblock methoxy poly(ethylene glycol)
      b-[poly(l-lactide)](n), MPEG-b-(PLLA)(n) (n = 2, 4, and 8), bridged with
      dendritic ester linkages. First, a new series of A(OH)(n)-shaped hydroxy end
      capped MPEG-(OH)(2), MPEG-(OH)(4), and MPEG-(OH)(8) bearing corresponding one- to
      three-generation dendritic ester moieties were efficiently derived from the
      starting MPEG (M(n) = 2 KDa) and 2,2'-bis(hydroxymethyl)propionic acid (Bis-HMPA)
      via ester coupling and a facile hydroxy protection-deprotection cycle, and then,
      chemical structures of these functional MPEG-(OH)(n) were characterized by
      nuclear magnetic resonance spectrometry (NMR) and MALDI-FTMS. Subsequently, by
      employing these MPEG-(OH)(n) as functional macroinitiators, new asymmetric
      AB(n)()-shaped amphiphilic MPEG-b-(PLLA)(2) S1, MPEG-b-(PLLA)(4) S2, and MPEG-b
      (PLLA)(8) S3 bridged with dendritic Bis-HMPA ester linkages of L1-L3 as well as
      linear structural MPEG-b-PLLA references (R1-R3) were synthesized through the
      SnOct(2)-catalyzed ring-opening polymerization (ROP) of l-lactide at 130 degrees
      C in m-xylene solution, and their structures were further examined by NMR and gel
      permeation chromatography (GPC). It was demonstrated that the functional MPEG
      (OH)(n) efficiently initiated the ROP of LLA, finally leading to successful
      formation of the AB(n)-shaped amphiphilic MPEG-b-(PLLA)(n) (n = 2, 4, and 8) with
      each PLLA arm weight close to 2 KDa and very narrow molecular weight
      distribution. Moreover, thermal history, crystallization, and spherulite
      morphologies were studied by means of differential scanning calorimeter (DSC),
      thermal gravimetric analyzer (TGA), and polarized microscope (POM) for these new
      structural amphiphilic S1-S3 as well as the linear R1-R3, intriguingly indicating
      a strong molecular architecture dependence of segmental crystallizability,
      spherulite morphology, and apparent crystal growth rate. Due to the favorable
      biodegradability and biocompatibility of the PLLA and MPEG, these results may
      therefore create new possibilities for these novel structural AB(n)-shaped
      amphiphilic MPEG-b-(PLLA)(n) as potential biomaterials.

PMID- 16903687
TI  - Columnar assembly of cyclic beta-amino acid functionalized with pyranose rings.
AB  - A novel cyclic trimer and tetramer of protected beta-glycamino acids were
      synthesized and investigated on conformation and assembly formation. A
      characteristic point of these cyclic beta-glycamino acids is their better
      solubility than other cyclic beta-amino acids due to the pyranose rings. Thus,
      the assembling process of the cyclic molecules could be examined by CD or NMR
      spectroscopy. FT-IR and NMR measurements and geometry optimization revealed a
      highly symmetric and planar conformation for each cyclic beta-peptide with all
      trans amide groups. The amide groups in the cyclic peptides took a vertical
      orientation against the cyclic skeleton to be suitably arranged for
      intermolecular hydrogen bonds, which should promote formation of molecular
      assembly in a columnar structure through molecular stacking. These cyclic beta
      peptides were successfully crystallized to yield rod-shaped molecular assemblies
      in nanometer sizes. Evidence for the columnar structure in the crystals was
      obtained by electron diffraction analysis, which showed a layer spacing of ca.
      4.8 A. Interestingly, the molecular assembly of the cyclic trimer showed a high
      aspect ratio, width less than 40 nm, and length more than 2 mum, suggesting
      stable molecular stacking in the column.

PMID- 16903686
TI  - Fibrillogenesis of collagen types I, II, and III with small leucine-rich
      proteoglycans decorin and biglycan.
AB  - Collagen has found use as a scaffold material for tissue engineering as well as a
      coating material for implants with a view to enhancing osseointegration through
      mimicry of the bone extracellular matrix in vivo. The aim of this study was to
      compare the collagen types I, II, and III with regard to their ability to bind
      the small leucine-rich proteoglycans (SLRPs) decorin and biglycan during
      fibrillogenesis in vitro in phosphate buffer. In addition, the influence of SLRPs
      on the proportion of collagen molecules incorporated into fibrils during
      fibrillogenesis in vitro at high and low ionic strength was investigated, as were
      their effects on the morphology of collagen fibrils and the speed of
      fibrillogenesis. Considerably more biglycan than decorin was bound by all three
      collagen types. Collagen II bound significantly more SLRPs in fibrils than
      collagen I and III. Decorin and biglycan decreased the proportion of collagen
      molecules of all three collagen types incorporated into fibrils in similar
      fashion. Biglycan affected neither fibril diameter nor the speed of
      fibrillogenesis. Decorin reduced the fibril diameter of all three collagen types.
      The differences in SLRP-binding ability between collagen types could be of
      significance when selecting collagen type and/or SLRPs as scaffold materials for
      tissue engineering or implant coatings.

PMID- 16903688
TI  - Synthetic biodegradable ionomers that engulf, store, and deliver intact proteins.
AB  - Telechelic anionic and cationic biodegradable ionomers capable of loading,
      storing, and releasing proteins are presented. Two different ionomers have been
      synthesized with either anionic or cationic end groups. The reaction was done
      quantitatively as shown by (1)H NMR. The swelling properties of the hydrophobic
      poly(trimethylene carbonate) polymer are contributed to the ionic end groups that
      display hydrophilic properties. Depending on the molecular weight of the ionomer,
      and also on the ionic charge, the materials swell differently in water, from
      approximately 50% for M(w) = 12 000 g/mol to approximately 500% when dealing with
      2000 g/mol. The high swelling led us to believe that it would be possible to load
      and release proteins preferably in a still active form. As models, two different
      proteins were chosen: hemoglobin and cytochrome c. The swelling and release study
      shows that both ionomers possess the capability to adsorb and later release the
      proteins with retained structure. Release measurements from both the swollen and
      dried states have been evaluated with similar results, showing that the dried
      state seems to release a little bit less than the swollen one. These kinds of
      materials should be interesting for a wide variety of applications where drug and
      protein release is wanted, as well as in applications such as protein separation
      media.

PMID- 16903689
TI  - pH-responsive poly(styrene-alt-maleic anhydride) alkylamide copolymers for
      intracellular drug delivery.
AB  - Many macromolecular therapeutics such as peptides, proteins, antisense
      oligodeoxynucleotides (ASODN), and short interfering RNA (siRNA) are active only
      in the cytoplasm or nucleus of targeted cells. Endocytosis is the primary route
      for cellular uptake of these molecules, which results in their accumulation in
      the endosomal-lysosomal trafficking pathway and loss of therapeutic activity. In
      this article, we describe the synthesis and pH-dependent membrane-destabilizing
      activity of a new "smart" polymer family that can be utilized to enhance the
      intracellular delivery of therapeutic macromolecules through the endosomal
      membrane barrier into the cytoplasm of targeted cells. These polymers are
      propylamine, butylamine, and pentylamine derivatives of poly(styrene-alt-maleic
      anhydride) (PSMA) copolymers. The PSMA-alkylamide derivatives are hydrophilic and
      membrane-inactive at physiological pH; however, they become hydrophobic and
      membrane-disruptive in response to endosomal pH values as measured by their
      hemolytic activity. Results show that the pH-dependent membrane-destabilizing
      activity of PSMA derivatives can be controlled by varying the length of the
      alkylamine group, the degree of modification of the copolymer, and the molecular
      weight of the PSMA copolymer backbone. Butylamine and pentylamine derivatives of
      PSMA copolymers exhibited more than 80% hemolysis at endosomal pH values, which
      suggests their potential as a platform of "smart" polymeric carriers for enhanced
      cytoplasmic delivery of a variety of therapeutic macromolecules.

PMID- 16903690
TI  - Synthesis and characterization of multiblock copolymers based on spider dragline
      silk proteins.
AB  - Spider dragline silk with its superlative tensile properties provides an ideal
      system to study the relationship between morphology and mechanical properties of
      a structural protein. Accordingly, we synthesized two hybrid multiblock
      copolymers by condensing poly(alanine) [(Ala)(5)] blocks of the structural
      proteins (spidroin MaSp1 and MaSp2) of spider dragline silk with different
      oligomers of isoprene (2200 and 5000 Da) having reactive end groups. The
      synthetic multiblock polymer displayed similar secondary structure to that of
      natural spidroin, the peptide segment forming a beta-sheet structure. These
      multiblock polymers showed a significant solubility in the component solvents.
      Moreover, the copolymer which contains the short polyisoprene segment would
      aggregate into a micellar-like structure, as observed by TEM.

PMID- 16903691
TI  - Novel silicon-containing polyurethanes from vegetable oils as renewable
      resources. Synthesis and properties.
AB  - Hydrosilylation of methyl 10-undecenoate (UDM) with phenyl
      tris(dimethylsiloxy)silane (PTDS) followed by a reduction of carboxylate groups
      was used to obtain a silicon-containing polyol with terminal primary hydroxyl
      groups (PSi194). Biobased silicon-containing polyurethanes, with a silicon
      content between 1.7% and 9.0%, were prepared from epoxidized methyl oleate-based
      polyether polyol (P184), PSi194, and 4,4'-methylenebis(phenyl isocyanate) (MDI).
      The thermal, mechanical, and flame-retardant properties of these materials were
      examined. The most notable change resulting from the incorporation of PSi194 is
      the appearance of melting endotherms of variable enthalpy and position and a
      downward shift in the T(g). The incorporation of silicon does not change the
      thermal stability but enhances the stability of the char under air atmosphere.
      Polyurethanes with higher silicon content no longer burn in ambient air without
      complementary oxygen, which suggests that these biobased materials are very
      interesting for applications that require fire resistance.

PMID- 16903692
TI  - Acetylation of polyethylenimine enhances gene delivery via weakened polymer/DNA
      interactions.
AB  - We previously reported that gene delivery efficiency of 25-kDa, branched
      polyethylenimine (PEI) increased upon acetylation of up to 43% of the primary
      amines with acetic anhydride. In the present work, we investigated the effects of
      further increasing the degree of acetylation and elucidated the source of the
      higher gene delivery efficiency. Despite reduced buffering capacity, gene
      delivery activity continued to increase (up to 58-fold in HEK293) with
      acetylation of up to 57% of primary amines but decreased at higher degrees of
      acetylation. Characterization of polymer-DNA interactions showed that acetylated
      polymers bind less strongly to DNA. Further, a fluorescence resonance energy
      transfer assay showed that increasing acetylation causes polyplexes to unpackage
      inside cells to a higher degree than polyplexes formed with unmodified PEI.
      Overall, the data suggest that the increased gene delivery activity may be
      attributable to an appropriate balance between polymer buffering capacity and
      strength of polymer/DNA interactions.

PMID- 16903693
TI  - In vivo and in vitro characterization of Ser477X mutations in
      polyhydroxyalkanoate (PHA) synthase 1 from Pseudomonas sp. 61-3: effects of
      beneficial mutations on enzymatic activity, substrate specificity, and molecular
      weight of PHA.
AB  - Evolutionary engineered polyhydroxyalkanoate (PHA) synthases from Pseudomonas sp.
      61-3 enhance PHA accumulation and enable the monomer composition of PHAs to be
      regulated. We characterized a newly screened Ser477Arg (S477R) mutant of PHA
      synthase by in vivo analyses of P(3-hydroxybutyrate) [P(3HB)] homopolymer and
      P(3HB-co-3-hydroxyalkanoate) [P(3HB-co-3HA)] copolymer productions in the
      recombinants of Escherichia coli. The results indicated that the S477R mutation
      contributed to a shift in substrate specificity to smaller monomers containing a
      3HB unit rather than to an enhancement in catalytic activity. Multiple mutations
      of S477R with other beneficial mutations, for example, Ser325Cys, exhibited
      synergistic effects on both an increase in PHA production (from 9 wt % to 21 wt
      %) and an alteration of substrate specificity. Furthermore, the effects of
      complete amino acid substitutions at position 477 were characterized in terms of
      in vivo PHA production and in vitro enzymatic activity. The five mutations,
      S477Ala(A)/Phe(F)/His(H)/Arg(R)/Tyr(Y), resulted in a shift in substrate
      specificity to smaller monomer units. The S477Gly(G) mutant greatly enhanced
      activity toward all different sizes of substrates with carbon numbers ranging
      from 4 to 12. These results indicated that the residue 477 contributes to both
      the catalytic activity and substrate specificity of PHA synthase. In recombinant
      E. coli, the S477A/F/G/H/R/Y mutations consistently led to increases (up to 6
      times that of wild-type enzyme) in weight average molecular weights of P(3HB)
      homopolymers. On the basis of our studies, we created a structural feasibility
      accounting for the mutational effects on enzymatic activity and substrate
      specificity of PHA synthase.

PMID- 16903694
TI  - Cell fouling resistance of polymer brushes grafted from ti substrates by surface
      initiated polymerization: effect of ethylene glycol side chain length.
AB  - This paper presents a comparative study on the antifouling properties of
      poly(ethylene glycol) (PEG)-based polymer coatings prepared by surface-initiated
      polymerization (SIP). Three types of poly(oligo(ethylene glycol) methyl ether
      methacrylate) (POEGMEMA) polymer thin films of approximate 100 nm thickness were
      grafted from a catechol initiator that was immobilized on a Ti substrate. OEGMEMA
      monomers containing side chains of 4, 9, and 23 EG units were used in surface
      initiated atom transfer radical polymerization (SI-ATRP) to form POEGMEMA-4, -9,
      and -23 polymer brushes. The chemical composition, thickness, and wettability of
      the polymer brushes were characterized by X-ray photoelectron spectroscopy (XPS),
      ellipsometry, and static water contact angle measurements, respectively. The
      dependence of antifouling performance on EG side chain length was systemically
      tested and compared by 3T3 fibroblast cell adhesion assays. Results from 4-h cell
      culture experiments revealed the complete absence of cell attachment on all the
      grafted Ti substrates. Excellent cell fouling resistance continued with little
      dependence on EG side chain length up to three weeks, after which long-term
      antifouling performance depended on the EG chain length as the grafted samples
      reached confluent cell coverage in 7, 10, and 11 weeks for POEGMEMA-4, -9, and 
      23, respectively.

PMID- 16903695
TI  - Nonspecific hydrophobic interactions of a repressor protein, PhaR, with poly[(R)
      3-hydroxybutyrate] film studied with a quartz crystal microbalance.
AB  - The gene expression for phasins (PhaP), which are predominantly
      polyhydroxyalkanoates (PHAs) granule-associated proteins, is regulated by a
      repressor protein of PhaR through the dual binding abilities of PhaR to the
      target DNAs and the granules. In this study, the binding functions of PhaR to
      poly[(R)-3-hydroxybutyrate] (P(3HB)) were investigated quantitatively by using a
      quartz crystal microbalance (QCM) technique. Adsorption of PhaR onto a melt
      crystallized film of P(3HB) (cr-P(3HB)) was detected as a negative frequency
      shift of the QCM. The time course of the frequency changes observed for PhaR
      adsorption was composed of a quick frequency decrease at an initial stage and a
      subsequent slower frequency decrease for several hours, indicating multilayered
      adsorption of PhaR molecules onto cr-P(3HB). The initial rapid adsorption, which
      corresponds to direct adsorption of PhaR molecules onto a bare surface of cr
      P(3HB), was a diffusion-controlled process. Strong interactions between PhaR and
      cr-P(3HB) were also observed as apparently irreversible adsorption. The
      comparative QCM measurement of PhaR adsorption onto various types of polymers
      with different aliphatic chemical structures revealed that PhaR was adsorbed onto
      the surfaces of polymers, including cr-P(3HB), mainly by nonspecific hydrophobic
      interactions. These results illustrate the high affinity and low specificity for
      adsorption of PhaR to P(3HB).

PMID- 16903696
TI  - High-resolution solid-state NMR of B-type amylose.

PMID- 16903697
TI  - Protein and peptide release from in situ gelling polymer.

PMID- 16903698
TI  - Excited-state mixed valence in transition metal complexes.
AB  - Mixed valence in the lowest-energy metal-to-ligand charge-transfer excited state
      of di-(4-acetylpyridine)tetraammineruthenium(II) complexes is defined and
      analyzed. The excited state has two interchangeably equivalent ligands with
      different oxidation states. The electronic absorption band energies, selection
      rules, and bandwidths are analyzed quantitatively in terms of the signs and
      orientations of the transition dipole moments, sign and magnitude of the
      coupling, and resonance Raman analysis of displaced normal modes.

PMID- 16903699
TI  - Highly diastereoselective oxidative addition of methyl iodide to a chiral square
      planar complex.
AB  - Oxidative addition of methyl iodide to the chiral square-planar complex
      IrI(CO)(duphos) shows a high level of diastereoselectivity. The basis for the
      diastereoselectivity of the reaction is best explained based on the crystal
      structure of IrI(CO)(duphos) in which methyl iodide approach across the two faces
      is differentiated by the chiral ligand.

PMID- 16903700
TI  - Cubic octanuclear aluminum fluoride phosphonate.
AB  - A crystalline complex [Al8F12{(CH3)2C(NH3)PO3}12] (1) was isolated from the
      supernatant of the hydrothermal reaction of gibbsite Al(OH)3 with 1-amino-1
      methyl-ethylphosphonic acid (AIPA) and the HF mineralizer. The single-crystal X
      ray diffraction analysis revealed a highly symmetrical cubic Al8F12 core with
      aluminum atoms at the corners, bridging fluorides spanning all edges, and 12
      bidentate bridging phosphonate ligands completing the octahedral coordination
      sphere of aluminum centers. The stability of the complex in solution was
      established by electrospray mass spectrometry and the high molecular symmetry
      (Th) was reflected in the appearance of single resonances in the 1H, 19F, and 31P
      NMR spectra.

PMID- 16903701
TI  - Luminescently tagged 2,2'-bipyridine complex of FeII: synthesis and photophysical
      studies of 4-[N-(2-anthryl)carbamoyl]-4'-methyl-2,2'-bipyridine.
AB  - The anthracene lumiphore was linked to the chelating ligand 2,2'-bipyridine,
      forming 4-[N-(2-anthryl)carbamoyl]-4'-methyl-2,2'-bipyridine (bpyAnth). Coupling
      through an amide linkage provides some electronic isolation of the anthracene
      lumiphore. Electrochemistry suggested little change of the anthracene oxidation
      whether free (1.35 V) linked to 2,2'-bipyridine as bpyAnth (1.30 V) or appended
      to Fe(II) (1.29 V). The bpyAnth ligand retained the structured luminescence
      characteristic of anthracene at 375, 400, 419, and 441 nm. This anthracene
      emission persists even when bpyAnth is complexed to an Fe(II) center. The complex
      [Fe(bpyAnth)3]2+ is emissive, in marked contrast to typical polyazine iron(II)
      complexes. This bpyAnth ligand serves as a luminescently tagged analogue of 2,2'
      bipyridine, useful for coordination to a variety of metals.

PMID- 16903702
TI  - Periodic density functional theory investigation of the uranyl ion sorption on
      the TiO2 rutile (110) face.
AB  - Periodic density functional theory calculations have been performed in order to
      study the uranyl ion sorption on the TiO2 rutile (110) face. From experimental
      measurements, two uranyl surface complexes have been observed and the two
      corresponding sorption sites have been identified. However, from a
      crystallographic point of view, three different sorption sites can be considered
      on this face. The corresponding three surface bidentate complexes were modeled
      and optimized, and their relative energies were calculated. Only 5 kJ/mol
      separates the two most stable structures, which correspond to the experimental
      ones. The third surface complex is nearly 10 kJ/mol less stable, in agreement
      with the fact that it was not observed experimentally.

PMID- 16903703
TI  - A supramolecular hexameric ring from alumazene and methylsulfonate.
AB  - A dealkylsilylation reaction of alumazene [2,6-(i-Pr)2C6H3NAlMe]3 (1) with
      trimethylsilyl methylsulfonate in a 1:2 molar ratio in toluene afforded a
      supramolecular cyclic hexamer {Me[2,6-(i-Pr)2C6H3NAl]3(O3SMe)2}6 (2) composed of
      six intact alumazene rings and possessing two types of bridging sulfonate groups.
      Changing the reagent molar ratio to 1:3 caused the third sulfonate to partially
      substitute the last alumazene methyl group in an eta2 fashion and introduced a
      disorder in the crystal lattice.

PMID- 16903704
TI  - Characterization of the first N2S(alkylthiolate)lead compound: a model for three
      coordinate lead in biological systems.
AB  - A new N2S(alkylthiolate)-coordinated Pb2+ compound {2-methyl-1-[methyl(2-pyridin
      2-ylethyl)amino]propane-2-thiolatolead perchlorate, [PATH-Pb][ClO4]} has been
      synthesized and characterized by X-ray diffraction and by 207Pb NMR. [PATH-Pb]+
      is the first reported three-coordinate Pb complex with an alkanethiolate ligand
      and, hence, is a good model for Pb-cysteine interactions in proteins. The Pb
      center displays distorted trigonal-planar geometry. The Pb-S bond lengths are
      extremely short (2.590(10) and 2.597(10) A for two distinct monomers in the unit
      cell). 207Pb NMR revealed a Pb resonance at 5318 ppm, much further downfield than
      Pb complexes with N and O ligation. Given recent evidence of three-coordinate Pb
      binding in proteins with cysteine-rich metal-binding sites, [PATH-Pb]+ is an
      important model for Pb sites in biological systems. Crystal data:
      C12H19N2SPbClO4, Mr = 529.99, monoclinic, P2(1)/n, a = 16.8297(9) A, b =
      11.9719(6) A, c = 17.0868(9) A, V = 3237.7(3) A3, and Z = 8.

PMID- 16903705
TI  - Two chiral metal clusters derived from nucleophilic addition of L-proline to di-2
      pyridyl ketone.
AB  - In the presence of cobalt (nickel) acetate, a chiral tetrahedral intermediate
      ligand of (S)-(C5NH4)2C(OH)(C4NH7CO2H) was first formed from the nucleophilic
      addition of l-proline as a secondary amine to ketone (di-2-pyridyl ketone). Based
      on the ligand synthesized in situ, two chiral tetranuclear isomorphous complexes
      1 and 2 with the formula
      {Na[M4L3(OAc)3](ClO4)(1.5)(H2O)(1.5)}(ClO4)(OH)(0.5).3H2O (M = Co, Ni) have been
      achieved. The Co4 cluster (1) behaves as a ferromagnet.

PMID- 16903706
TI  - A tantalum(V) carbene complex: formation of a carbene-bis(phenoxide) ligand by
      sequential proton and hydride abstraction.
AB  - Proton and subsequent hydride abstraction from the bis(phenoxide) ligand of the
      trimethyltantalum(V) complex affords a cationic tantalum(V) carbene complex, in
      which two phenoxide groups are linked to the carbene center. The electrophilic
      nature of the carbene functionality is demonstrated by the reaction with PPh3.

PMID- 16903707
TI  - Neutral {Fe(NO)2}9 dinitrosyliron complex (DNIC) [(SC6H4-o-NHCOPh)(Im)Fe(NO)2]
      (Im = imidazole): interconversion among the anionic/neutral {Fe(NO)2}9 DNICs and
      Roussin's red ester.
AB  - A neutral {Fe(NO)2}9 dinitrosyliron complex (DNIC) [(SC6H4-o-NHCOPh)(Im)Fe(NO)2]
      (Im = imidazole; 2) was prepared by the reaction of [Fe(mu-SC6H4-o-NHCOPh)(NO)2]2
      (1) and 2 equiv of imidazole. In the synthesis of the anionic {Fe(NO)2}9 DNIC
      [(SC6H4-o-NHCOPh)2Fe(NO)2]- (3), thiolate [SC6H4-o-NHCOPh]- triggers ligand
      substitution of DNIC 2 to yield DNIC 3. At 298 K, complexes 2 and 3 exhibit well
      resolved nine- and five-line electron paramagnetic resonance (EPR) signals at g =
      2.031 and 2.029, respectively, the characteristic g value of DNICs. The facile
      interconversions among the neutral {Fe(NO)2}9 complex 2, the anionic {Fe(NO)2}9
      complex 3, and Roussin's red ester 1 were demonstrated. The EPR spectrum (the
      pattern of hyperfine splitting) in combination with the IR nu(NO) (the relative
      position of the nu(NO) stretching frequencies) spectrum may serve as an efficient
      tool for the discrimination of the anionic {Fe(NO)2}9 DNICs, the neutral
      {Fe(NO)2}9 DNICs, and Roussin's red ester.

PMID- 16903709
TI  - Technetium complexes with triazacyclononane.
AB  - [NBu4][TcOCl4] reacts with ethylene glycol and 1,4,7-triazacyclononane (tacn) in
      MeOH under the formation of the deep-blue oxotechnetium(V) cation
      [TcO(OC2H4O)(tacn)]+, which can readily be oxidized by air to give the stable
      technetium(VII) compound [TcO3(tacn)]+. The reaction with aqueous HCl results in
      reduction and the formation of the cationic technetium(III) complex
      [TcCl2(OH2)(tacn)]Cl. The products were isolated in crystalline form and studied
      spectroscopically and by X-ray diffraction.

PMID- 16903708
TI  - Hydrothermal synthesis of a three-dimensional organic-inorganic hybrid network
      formed by poly(oxomolybdophosphate) anions and nickel coordination cations.
AB  - A novel organic-inorganic hybrid nickel molybdenum(V) phosphate has been
      synthesized hydrothermally and characterized by single-crystal X-ray diffraction,
      thermogravimetric analysis, and magnetic susceptibility. The structure consists
      of poly(oxomolybdophosphate) anions linked by both Ni(II) cations and 4,4
      bipyridine bridging ligands to form a three-dimensional open-framework structure
      with large cavities where the uncoordinated 4,4'-bipyridinium cations and lattice
      water molecules are located. This is the first example of an extended framework
      solid containing poly(oxomolybdophosphate) anions interconnected by both
      transition-metal complexes and organic moieties. Crystal data: (4,4'
      H2bpy)[Ni(4,4'-bpy)(H2O)2Ni(0.5)Mo6(OH)3O12(HPO4)4].2H2O, orthorhombic, space
      group Pccn (No. 56), a = 27.745(2) A, b = 16.158(1) A, c = 22.819(2) A, V
      =10230.3(1) A(3), and Z = 8.

PMID- 16903710
TI  - Trinuclear gold(I) triazolates: a new class of wide-band phosphors and sensors.
AB  - A new cyclic gold(I) triazolate trimer, [Au(3,5-i-Pr2Tz)]3 (1), exhibits fully
      overlapping aurophilically bonded dimer-of-trimer units that lead to multiple
      phosphorescence bands in both the solid state and solution. The conformation of
      the hexanuclear unit exhibits reversible interconversion between C2 and D3
      effective symmetries, depending on the crystal temperature or solution
      concentration, the variation of which leads to isoemissive and isosbestic points.
      Solutions of 1 exhibit remarkable quenching properties that demonstrate molecular
      recognition with high selectivity and hypersensitivity for some reagents, as
      influenced by protonation via Bronsted acids, pi intercalation, and/or energy
      transfer. The quenched phosphorescence of 1 by acetic acids can be regenerated by
      NEt3.

PMID- 16903711
TI  - Air-stable titanium alkoxide based metal-organic framework as an initiator for
      ring-opening polymerization of cyclic esters.
AB  - An air-stable titanium-organic framework, prepared from Ti(OiPr)4 and 1,4
      butanediol, has been characterized via single-crystal X-ray diffraction,
      revealing a unique supramolecular structure. Its functionality as a highly active
      initiator for the ring-opening polymerization of cyclic esters is demonstrated. A
      discrete titanium trimer containing the related ligand (2R,3R)-2,3-butanediol has
      also been prepared, and it shows analogous activity as a polymerization
      initiator.

PMID- 16903712
TI  - Stabilization by a divalent transition metal in lead indium quaternary selenide,
      Fe(0.47)Pb(8.04)In(17.37)Se(34), and specific indium coordination.
AB  - Single crystals of the first M-Pb-In-Se quaternary selenide,
      Fe(0.47)Pb(8.04)In(17.37)Se34, with the structure stabilized by a divalent
      transition metal (M = Fe), have been grown by a solid-state reaction. The Fe(II)
      ions partially occupy at the In sites with various Fe/In ratios. Thus, a new
      crystal structure is evolved by partially occupied minor Fe atoms at In sites. A
      part of the In atoms shows remarkably distorted octahedral coordination. This
      compound shows relatively high conductivity (approximately 40 S/m at 300 K) with
      a narrow-band-gap-type semiconducting property (Ea = 0.078 eV).

PMID- 16903713
TI  - Hydrogen bonding cavities regulating redox behavior and binding of metal-bound
      ligands.
AB  - Binding of 3,5-di-tert-butyl-1,2-benzochatechol (H2DTBC) at Zn(II) complexes of a
      tetradentate, tripodal ligand L is significantly enhanced (36-4.6 x 10(4) fold),
      and its reduction potential shifted (90-270 mV) to more positive values by
      introducing one to three amino hydrogen bond donors. The structure of one of the
      [(L)Zn(DTBC)] complexes is reported and shows intramolecular N-H...O hydrogen
      bonding between the ligand-based amino group and the Zn(II)-bound chatecholate,
      which provides an explanation for the observed behavior.

PMID- 16903714
TI  - Bi3+/M2+ oxyphosphate: a continuous series of polycationic species from the 1D
      single chain to the 2D planes. Part 1: From HREM images to crystal-structure
      deduction.
AB  - This work deals with the crystal-structure deduction of new structural types of
      Bi3+-M2+ oxyphosphates (M is a transition element) from HREM images. Previous
      studies showed the unequivocal attribution of particular HREM contrasts to the
      corresponding Bi/M/O-based polycationic species in similar materials. On this
      basis, the examination of isolated crystallites of polyphased samples led to new
      HREM contrasts assigned to new polycationic species in three new structural
      types. This helped us to solve one crystal structure, and the two other forms
      have been deduced through HREM image decoding. It helped to model the
      investigated materials from the structural point of view as well as the chemical
      one. The three assumed crystal structures are formed by polycationic ribbons, n
      tetrahedra wide, surrounded by PO4 groups, as already encountered in these series
      of oxyphosphates. However, here we deal with the original n= 4-6 cases, whereas,
      up to this work, only the n= 1-3 ribbons have been reported. The greater size of
      ribbons is associated with particular structural modifications responsible for
      complex HREM contrasts. The validity of the proposed models is verified in Part 2
      of this work.

PMID- 16903715
TI  - Bi3+/M2+ oxyphosphate: a continuous series of polycationic species from the 1D
      single chain to the 2D planes. Part 2: Crystal structure of three original
      structural types showing a combination of new ribbonlike polycations.
AB  - With the assistance of structural models deduced from the high-resolution
      electron microscope (HREM) investigation presented in Part 1 of this work, three
      new structural types were pointed out in Bi2O3-MO-P2O5 ternary systems. Their
      crystal structures are built on the arrangement of 2D polycationic ribbons formed
      of edge-sharing O(Bi,M)4 tetrahedra and isolated by PO4 groups. Prior to this
      study, materials with ribbons up to n = 3 tetrahedra wide have been discovered.
      The original structures presented here display longer n = 4-6 cases, which
      suggests a possible continuous series of polycationic entities that range from
      the single chain (one tetrahedron wide) to the infinite [Bi2O2]2+ Aurivillius
      layer. The ribbons with n > 3 show strong structural modifications that are able
      to bring a good ribbon-phosphate cohesion. In addition to these fascinating
      structural results, this work fully confirms the validity of the decoding
      established from HREM images of a single crystallite in inhomogeneous mixtures.

PMID- 16903716
TI  - Hydrothermal synthesis and characterization of two cobalt phosphates based on
      double-four-ring units with fluorine-occlusion and phosphite-substitution
      modifications.
AB  - Two new fluorinated microporous cobalt phosphates,
      (H2en)0.5[F(0.25)Co(H(0.5)PO4)0.5(PO4)0.5].0.25H2O (1) and (H2en)0.5[Fx(H2O)0.25(
      x)Co(HPO3)x(PO4)1-x].0.25H2O (x = 0.17; 2), have been synthesized from different
      P sources, H3PO4 and H3PO3, in the presence of ethylenediamine and F ions. Both
      structures of 1 and 2 are based on the similar secondary building unit of a
      double four ring (D4R). 1 crystallizes in the orthorhombic space group Cmcm with
      a = 14.895(1) A, b = 9.7133(9) A, c = 13.688(1) A, V = 1980.4(3) A(3), and Z = 16
      and is built up from fully F-occluded double-four-ring units via corner-sharing
      Co and P polyhedra and edge-sharing Co polyhedra. 2 crystallizes in the
      tetragonal space group /42m with a = 10.2033(4) A, c = 9.5545(9) A, V = 994.7(1)
      A(3), and Z = 8 and adopts an ACO-type framework with strict alternation of
      corner-sharing Co and P polyhedra. On the basis of the evidence from ion
      chromatography studies and elemental analyses, 2 contains both phosphate and
      phosphite ions, and the amount of F ions in 2 is the same as the amount of
      phosphite ions. This implies that some PO4(3-) groups in 2 are substituted by
      HPO3(2-) groups with the same amount of F(-) occlusion in the center of D4R as
      charge compensation. Magnetic susceptibility measurements of both 1 and 2 appear
      that they contain mainly antiferromagnetic interaction (theta = -27.8 K for 1 and
      -35.0 K for 2). However, the magnetic coupling is much more complicated in
      compound 1 because of the Co-O-Co linkages in it. Low-field temperature-dependent
      magnetization curves of 1 showed spontaneous magnetization in the form of two
      continuous bumps, one sharp and one broad. This may be related to the temperature
      dependence of two related but different types of spin canting. At 2 K, 1 also
      showed a large coercive field of about 5000 Oe.

PMID- 16903717
TI  - Neutral and cationic complexes with P-bonded 2-pyridylphosphines as N-donor
      ligands toward rhodium. Electrical charge vs steric hindrance on the
      conformational control.
AB  - Bimetallic palladium(II)-rhodium(I) and gold(I)-rhodium(I) complexes of the type
      [(4,4'-Me2-bipy)(C6F5)Pd(mu-PPh(3-n)Pyn)Rh(diene)](BF4)2 and [(C6F5)Au(mu-PPh(3
      n)Pyn)Rh(diene)](BF4) (n = 2, 3; Py = 2-pyridyl) have been synthesized. The P
      donor atom of the bridging ligands (mu-PPh(3-n)Pyn) is coordinated to the Pd or
      to the Au center. The resulting complexes react with [Rh(diolefin)(solv)2]+ (solv
      = acetone) in a way similar to pyrazolylborates, affording square-planar or
      pentacoordinated rhodium complexes with two or the three N-donor ends chelating
      the Rh atom. The metallacycles formed upon chelation can adopt one of two
      conformations in the square-planar Rh(I) complexes, either bringing the other
      metal close to the Rh center or bringing it to a remote position. The first
      conformation is preferred for the gold P-coordinated complexes and the second for
      the palladium complexes. The X-ray structures of [(4,4'-Me2-bipy)](C6F5)Pd(mu
      PPhPy2)Rh(COD)](BF4)2 (COD = 1,5 cyclooctadiene) and [Au(C6F5)(mu
      PPhPy2)Rh(TFB)](BF4) (TFB = 5,6,7,8-tetrafuoro-1,4-dihydro-1,4-etenonaphthalene)
      are reported.

PMID- 16903718
TI  - Crystallographic evidence of nitrate-pi interactions involving the electron
      deficient 1,3,5-triazine ring.
AB  - The reaction of Zn(NO3)2.6H2O or Cu(NO3)2.3H2O with the star-shaped ligand 2,4,6
      tris(di-2-picolylamino)[1,3,5]triazine (dipicatriz) in acetonitrile results in
      the formation of the mono- or trinuclear coordination compounds
      [Zn(dipicatriz)(NO3)2] (1), [Zn3(dipicatriz)(NO3)6](CH3CN)3 (2), and
      [Cu3(dipicatriz)(NO3)2(H2O)6](NO3)4 (3), depending on the metal-to-ligand ratios
      used during the crystallization process. Their crystal structures exhibit unique
      supramolecular interactions. Compounds 1 and 2 show anion-pi interactions between
      coordinated nitrate ions and the s-triazine ring. Compound 3 exhibits remarkable
      interactions between two noncoordinated nitrate anions and the two faces of the
      electron-deficient heteroaromatic ring, corroborating earlier theoretical
      investigations in this area. New theoretical investigations have been carried out
      on nitrate-pi interactions, taking into account the particular position of the
      anion toward the aromatic ring observed in the crystal structures.

PMID- 16903719
TI  - Tetranuclear copper(II) complexes bridged by alpha-D-glucose-1-phosphate and
      incorporation of sugar acids through the Cu4 core structural changes.
AB  - Tetranuclear copper(II) complexes containing alpha-D-glucose-1-phosphate (alpha-D
      Glc-1P), [Cu4(mu-OH){mu-(alpha-D-Glc-1P)}2(bpy)4(H2O)2]X3 [X = NO3 (1a), Cl (1b),
      Br (1c)], and [Cu4(mu-OH){mu-(alpha-D-Glc-1P)}2(phen)4(H2O)2](NO3)3 (2) were
      prepared by reacting the copper(II) salt with Na2[alpha-D-Glc-1P] in the presence
      of diimine ancillary ligands, and the structure of 2 was characterized by X-ray
      crystallography to comprise four {Cu(phen)}2+ fragments connected by the two
      sugar phosphate dianions in 1,3-O,O' and 1,1-O mu4-bridging fashion as well as a
      mu-hydroxo anion. The crystal structure of 2 involves two chemically independent
      complex cations in which the C2 enantiomeric structure for the trapezoidal
      tetracopper(II) framework is switched according to the orientation of the alpha-D
      glucopyranosyl moieties. Temperature-dependent magnetic susceptibility data of 1a
      indicated that antiferromagnetic spin coupling is operative between the two metal
      ions joined by the hydroxo bridge (J = -52 cm(-1)) while antiferromagnetic
      interaction through the Cu-O-Cu sugar phosphate bridges is weak (J = -13 cm(-1)).
      Complex 1a readily reacted with carboxylic acids to afford the tetranuclear
      copper(II) complexes, [Cu4{mu-(alpha-D-Glc-1P)}2(mu-CA)2(bpy)4](NO3)2 [CA =
      CH3COO (3), o-C6H4(COO)(COOH) (4)]. Reactions with m-phenylenediacetic acid [m
      C6H4(CH2COOH)2] also gave the discrete tetracopper(II) cationic complex [Cu4{mu
      (alpha-D-Glc-1P)}2(mu-m-C6H4(CH2COO)(CH2COOH))2(bpy)4](NO3)2 (5a) as well as the
      cluster polymer formulated as {[Cu4{mu-(alpha-D-Glc-1P)}2(mu-m
      C6H4(CH2COO)2)(bpy)4](NO3)2}n (5b). The tetracopper structure of 1a is converted
      into a symmetrical rectangular core in complexes 3, 4, and 5b, where the hydroxo
      bridge is dissociated and, instead, two carboxylate anions bridge another pair of
      Cu(II) ions in a 1,1-O monodentate fashion. The similar reactions were applied to
      incorporate sugar acids onto the tetranuclear copper(II) centers. Reactions of 1a
      with delta-D-gluconolactone, D-glucuronic acid, or D-glucaric acid in
      dimethylformamide resulted in the formation of discrete tetracopper complexes
      with sugar acids, [Cu4{mu-(alpha-D-Glc-1P)}2(mu-SA)2(bpy)4](NO3)2 [SA = D
      gluconate (6), D-glucuronate (7), D-glucarateH (8a)]. The structures of 6 and 7
      were determined by X-ray crystallography to be almost identical with that of 3
      with additional chelating coordination of the C-2 hydroxyl group of D-gluconate
      moieties (6) or the C-5 cyclic O atom of D-glucuronate units (7). Those with D
      glucaric acid and D-lactobionic acid afforded chiral one-dimensional polymers,
      {[Cu4{mu-(alpha-D-Glc-1P)}2(mu-D-glucarate)(bpy)4](NO3)2}n (8b) and {[Cu4{mu
      (alpha-D-Glc-1P)}2(mu-D-lactobionate)(bpy)4(H2O)2](NO3)3}n (9), respectively, in
      which the D-Glc-1P-bridged tetracopper(II) units are connected by sugar acid
      moieties through the C-1 and C-6 carboxylate O atoms in 8b and the C-1
      carboxylate and C-6 alkoxy O atoms of the gluconate chain in 9. When complex 7
      containing d-glucuronate moieties was heated in water, the mononuclear copper(II)
      complex with 2-dihydroxy malonate, [Cu(mu-O2CC(OH)2CO2)(bpy)] (10), and the
      dicopper(II) complex with oxalate, [Cu2(mu-C2O4)(bpy)2(H2O)2](NO3)2 (11), were
      obtained as a result of oxidative degradation of the carbohydrates through C-C
      bond cleavage reactions.

PMID- 16903720
TI  - Hydrothermal synthesis of rare-earth fluoride nanocrystals.
AB  - In this paper, a hydrothermal synthetic route has been developed to prepare a
      class of rare-earth fluoride nanocrystals, which have shown gradual changes in
      growth modes with decreasing ionic radii and may serve as a model system for
      studying the underlying principle in the controlled growth of rare-earth
      nanocrystals. Furthermore, we demonstrate the functionalization of these
      nanocrystals by means of doping, which have shown visible-to-the-naked-eye green
      up-conversion emissions and may find application in biological labeling fields.

PMID- 16903721
TI  - Aggregation in nanobundles and the effect of diverse environments on the solution
      phase photochemistry and photophysics of -Re(CO)3L+ (L = 1,10-phenanthroline,
      2,2'-bipyridine) pendants bonded to poly(4-vinylpyridine).
AB  - The UV-vis spectroscopy and photochemical properties of {(vpy-[Re(CO)3(2,2'
      bpy)])m(vpy-[Re(CO)3(phen)])n(vpy)p}(CF3SO3)(m+n)}, vpy = 4-vinylpyridine, m =
      131, n = 131 or m = 200, n = 150, and m + n + p = 600, were investigated in
      solution phase. The polymers exist in solution as aggregates of polymer strands
      with radii as large as approximately 10(2) nm. Given the size of the poly-vpy
      backbone, the aggregates must contain a large number of strands. The luminescence
      spectrum exhibits a strong resemblance to the emission spectrum of {(vpy
      [Re(CO)3(phen)])200(vpy)400}(CF3SO3)200. The existence of Re(I) chromophores in
      diverse environments was shown by the intrinsic kinetics of the luminescence, the
      decay kinetics of the MLCT excited states observed by time resolved-absorption
      spectroscopy, and the quenching of the luminescence by various quenchers. Redox
      reactions of the MLCT excited states with the quenchers were responsible for the
      luminescence quenching. While static quenching resulted when Cu(II) and Fe(III)
      EDTA complexes were the quenchers, a dynamic quenching resulted with Fe(CN)6(4-)
      or 2,2',2' '-triethanolamine, TEOA. The photochemical and photophysical
      properties of the mixed-pendant polymers have been discussed in terms of arrays
      of MLCT excited states whose energies are determined by the diverse environments
      of the Re(I) chromophores. Conversions (with and without radiation) of the upper
      energy MLCT excited states to the ground state and lower-energy MLCT excited
      states and the latter excited state to the ground state account for the
      experimental results.

PMID- 16903722
TI  - Copper(I) coordination polymers [{Cu(mu-X)}2{RP(mu-NtBu)}2]n (R = OC6H4OMe-o; X =
      Cl, Br, and I) and their reversible conversion into mononuclear complexes
      [CuX{(RP(mu-NtBu)2}2]: synthesis and structural characterization.
AB  - The reactions of cyclodiphosphazane cis-[tBuNP(OC6H4OMe-o)]2 (1) with 2 equiv of
      CuX in acetonitrile afforded one-dimensional Cu(I) coordination polymers
      [Cu2X2{tBuNP(OC6H4OMe-o)}2]n (2, X = Cl; 3, X = Br; 4, X = I). The crystal
      structures of 2 and 4 reveal a zigzag arrangement of [P(mu-N)(2)P] and [Cu(mu
      X)(2)Cu] units in an alternating manner to form one-dimensional Cu(I)
      coordination polymers. The reaction between 1 and CuX in a 2:1 ratio afforded
      mononuclear tricoordinated copper(I) complexes of the type [CuX{(tBuNP(OC6H4OMe
      o))2}2] (5, X = Cl; 6, X = Br; 7, X = I). The single-crystal structures were
      established for the mononuclear copper(I) complexes 5 and 6. When the reactant
      ratios are 1:1, the formation of a mixture of polymeric and mononuclear products
      was observed. The Cu(I) polymers (2-4) were converted into the mononuclear
      complexes (5-7) by reacting with 3 equiv of 1 in dimethyl sulfoxide. Similarly,
      the mononuclear complexes (5-7) were converted into the corresponding polymeric
      complexes (2-4) by reacting with 3 equiv of copper(I) halide under mild reaction
      conditions.

PMID- 16903723
TI  - Two-dimensional indium sulfide framework constructed from pentasupertetrahedral
      p1 and supertetrahedral t2 clusters.
AB  - A new open-framework indium sulfide ([In12S24H2]10-) constructed from
      pentasupertetrahedral sulfide clusters ([In8S17H],9- P1) and supertetrahedral
      sulfide clusters ([In4S10H],7-) T2) has been prepared through hydrothermal
      synthesis. Unlike previously reported P1 clusters that require divalent metal
      cations, the P1 cluster reported here consists of only trivalent ions (In3+) and
      is the only known example of tetrahedral clusters with a core sulfur site bonded
      to four trivalent ions. Each P1 cluster is joined to three T2 clusters (vice
      versa) to form an infinite two-dimensional sheet stacked along the
      crystallographic c-axis. In contrast with known three-dimensional open-framework
      indium sulfides in which locations of extraframework amines are rarely known due
      to disorder, structure-directing amine molecules are much less disordered as a
      result of host-guest N-H...S hydrogen bonding. The UV-vis diffuse reflectance
      spectrum shows that this material is a wide band gap semiconductor.

PMID- 16903724
TI  - Oxacalix[3]arene complexes with the ReI(CO)3 fragment.
AB  - Oxacalix[3]arenes p-methyloxacalix[3]arene (L(1)), p-isopropyloxacalix[3]arene
      (L2), and p-ethoxycarbonyloxacalix[3]arene (L3) are able to bind the Re(I)(CO)3
      moiety with two of their three phenol-O atoms and one of their ether-O atoms. The
      monoanionic complexes were isolated in the salts (DBUH)[Re(CO)3(L1H-2)].L1 (1)
      and (NEt4)[Re(CO)3(L2H-2)].L2.0.5 MeCN (2) (DBU = 1,8-diazabicyclo[5.4.0]undec-7
      ene). Over the course of its reaction with (NEt4)(2)[Re(CO)3Br(3)] and DBU, p
      ethoxycarbonyloxacalix[3]arene decomposes to form [{Re(CO)3(L4H-2)}2] (3) {L4 = 1
      (5-ethoxycarbonyl-2-hydroxy-3-hydroxymethyl-benzyl)-2,3,4,6,7,8,9,10-octahydro
      pyrimido[1,2-a]azepin-1-ium. The expected monoanion [Re(CO)3(L3H-2)]- (4) was
      identified by 13C NMR and mass spectra.

PMID- 16903725
TI  - Coordination polymers with end-on azido and pyridine carboxylate N-oxide bridges
      displaying long-range magnetic ordering with low dimensional character.
AB  - A series of 2D and one 3D transition-metal-azido coordination polymers with
      pyridine carboxylate N-oxide, isonicotinate N-oxide (INO), and nicotinate N-oxide
      (NNO) as the coligands were synthesized by a hydrothermal method and structurally
      and magnetically characterized. These complexes have the formulas
      [M(L)(N3)(H2O)]n (L = INO and M = Mn, 1.Mn; Co, 2.Co; Ni, 3.Ni and L = NNO and M
      = Mn, 4.Mn; Co, 5.Co; Ni, 6.Ni) and [Cu(L)(N3)(H2O)(0.5)]n (L = INO, 7.Cu; NNO,
      8.Cu). All complexes consist of end-on azido and syn-syn carboxylato mixed
      bridged M-N(3)/COO chains that are further linked by the pyridine N-oxide group
      of the INO or NNO to give rise to 2D layered structures for 1.Mn, 2.Co, 3.Ni,
      4.Mn, 5.Co, 6.Ni, and 8.Cu and a 3D framework for 7.Cu. The high-temperature
      magnetic susceptibilities are dominated by low-dimensional behavior while long
      range ordering sets in at low temperatures. The Mn complexes are
      antiferromagnets, and the others are metamagnets. In addition, 5.Co exhibits slow
      magnetic relaxation behavior at low temperatures. The metamagnetism in each case
      is due to strong intrachain ferromagnetic interactions and weak interchain
      antiferromagnetic ones.

PMID- 16903726
TI  - Synthesis and characterization of imidocubanes with exocube Ge(IV) and Sn(IV)
      substituents: [M(mu3-NGeMe3)]4 (M = Sn, Ge, Pb); [Sn(mu3-NSnMe3)]4.
AB  - The heteroleptic lithium amide, [(Me3Sn)(Me3Ge)NLi.(Et2O)]2 (2), reacts with
      MCl(2) (M = Sn, Ge, Pb) to yield the corresponding cubane complexes [M(mu3
      NGeMe3)]4 [M = Sn (3), Ge (4), Pb (5)]. In an analogous reaction with SnCl2, the
      lithium stannylamide, [(Me3Sn)2NLi.(Et2O)]2 (1), produces the mixed-valent Sn
      congener [Sn(mu3-NSnMe3)]4 (6). All imidocubanes contain both di- and tetravalent
      group 14 metals that are bridged by N. These structures are comprised of M4N4 (M
      = Sn, Pb, Ge) cores that possess varying distortion from perfect cube geometry.
      The Pb derivative (5) exhibits enhanced volatility and vapor-phase integrity.

PMID- 16903727
TI  - High-nuclearity manganese and iron complexes with the anionic ligand methyl
      salicylimidate.
AB  - The three novel clusters [Mn6O4(OMe)2(OAc)4(Mesalim)4] (3),
      [Mn8O2(OH)2(OMe)12(OAc)2(Mesalim)4] (4), and [Fe10O4(OMe)14Cl2(Mesalim)6] (5)
      have been synthesized from a simple bidentate ligand HMesalim (HMesalim = methyl
      salicylimidate). Starting from the mononuclear complex
      [Mn(Mesalim)2(OAc)(MeOH)].MeOH (1), either the hexanuclear complex 3 or the
      octanuclear complex 4 is obtained after recrystallization, depending upon the
      reaction conditions and solvents used. Similarly, starting from the purple
      colored mononuclear complex [Fe(Mesalim)2Cl] (2), the orange-colored decanuclear
      iron(III) cluster 5 has been obtained upon recrystallization from methanol.
      Complex 3, which could also be prepared directly from manganese acetate and the
      ligand, has a face-sharing double-cubane [Mn6O6] core, unique in transition metal
      chemistry. Compounds 4 and 5 are composed of [M3O4] partial cubanes. All
      complexes belong to a class of oxo-bridged cubic close-packed molecular clusters
      resembling the metal oxide/hydroxide ores. Complex 4 exhibits intramolecular
      ferromagnetic interactions, as evidenced from dc magnetic susceptibility studies
      (1.8-300 K), resulting in a high-spin ground state, probably with S(T) = 8.
      Complex 4 displays single molecule magnet behavior as indicated by frequency and
      temperature dependences of its ac susceptibility. An Arrhenius plot gave
      relatively large experimental activation energy of 36.0 K. The magnetic
      properties of complexes 3 and 5 are dominated by antiferromagnetic interactions
      leading to zero-spin ground states.

PMID- 16903728
TI  - Dimers of heptapnictide anions: As14 4- and P14 4- in the crystal structures of
      [Rb(18-crown-6)]4As14.6NH3 and [Li(NH3)4]4P14.NH3.
AB  - Compounds [Rb(18-crown-6)]4As14.6NH3 (1) and [Li(NH3)4]4P14.NH3 (2) were prepared
      by the reaction of Rb4As6 with SbPh3 and 18-crown-6 and by the reduction of white
      phosphorus with elemental lithium in liquid ammonia, respectively. Both were
      characterized by low-temperature single-crystal X-ray structure analysis. They
      were found to contain the Ci symmetrical Pn14(4-) anion (Pn = P, As), which
      consists of two nortricyclane-like Pn7-cages connected by a single bond.
      Molecular complexes of [Rb(18-crown-6)(NH3)]2[Rb(18-crown-6)]2As14 are formed in
      1, which are connected to fanfold sheets via N-H...O bonds. The anion is isolated
      in 2, and N-H...N bonds result in the formation of {[Li(NH3)4](mu
      NH3)2[Li(NH3)4]}2+ cationic complexes.

PMID- 16903729
TI  - 13C NMR studies of the electronic structure of low-spin iron(III)
      tetraphenylchlorin complexes.
AB  - A series of low-spin six-coordinate (tetraphenylchlorinato)iron(III) complexes
      [Fe(TPC)(L)2]+/- (L = 1-MeIm, CN-, 4-CNPy, and (t)BuNC) have been prepared, and
      their (13)C NMR spectra have been examined to reveal the electronic structure.
      These complexes exist as the mixture of the two isomers with the (d(xy))2(d(xz),
      d(yz))3 and (d(xz), d(yz))4(d(xy))1 ground states. Contribution of the (d(xz),
      d(yz))4(d(xy))1 isomer has increased as the axial ligand changes from 1-MeIm, to
      CN(-) (in CD2Cl2 solution), CN- (in CD(3)OD solution), and 4-CNPy, and then to
      tBuNC as revealed by the meso and pyrroline carbon chemical shifts; the meso
      carbon signals at 146 and -19 ppm in [Fe(TPC)(1-MeIm)2]+ shifted to 763 and 700
      ppm in [Fe(TPC)(tBuNC)2]+. In the case of the CN- complex, the population of the
      (d(xz), d(yz))4(d(xy))1 isomer has increased to a great extent when the solvent
      is changed from CD2Cl2 to CD3OD. The result is ascribed to the stabilization of
      the d(xz) and d(yz) orbitals of iron(III) caused by the hydrogen bonding between
      methanol and the coordinated cyanide ligand. Comparison of the 13C NMR data of
      the TPC complexes with those of the TPP, OEP, and OEC complexes has revealed that
      the populations of the (d(xz), d(yz))4(d(xy))1 isomer in TPC complexes are much
      larger than those in the corresponding TPP, OEC, and OEP complexes carrying the
      same axial ligands.

PMID- 16903730
TI  - Carbon dioxide fixation by an unprecedented hydroxo lead-chromium carbonyl
      complex: synthesis, reactivity, and theoretical calculations.
AB  - The novel hydroxo-bridged dimeric lead-chromium carbonyl complex
      [Et4N]2[{PbCr2(CO)10}2(mu-OH)2] ([Et4N]2[1]) was synthesized from the reaction of
      PbCl2 and Cr(CO)6 followed by metathesis with [Et4N]Br in a KOH/MeOH solution.
      The X-ray crystallographic structure shows that dianion 1 consists of two
      Pb{Cr(CO)5}2 units bridged by two hydroxo fragments in which the Pb atoms are
      further coordinated with two Cr(CO)5 groups, resulting in a distorted tetrahedral
      geometry. A CO2 molecule can insert itself into dianion 1 to form two new
      carbonate complexes, [Et(4)N]2[{PbCr2(CO)10}(CO3)] ([Et4N]2[2]) and
      [Et4N]2[{PbCr2(CO)10}2(CO3)] ([Et4N]2[3]), depending on the reaction conditions.
      In addition, complex 2 can be transformed into 3 in CH2Cl2 solution at an
      elevated temperature. While the carbonate group in dianion 2 is bonded to one Pb
      atom, which is coordinated with two Cr(CO)5 fragments, the carbonate group in 3
      bridges the two Pb centers in a mu-1kappa2OO':2kappa2OO' fashion in which each Pb
      atom is further bonded to two Cr(CO)5 moieties. Complexes 2 and 3 can be
      converted back the hydroxo complex 1 under appropriate conditions. All three
      unprecedented lead-chromium compounds, 1-3, were fully characterized by
      spectroscopic methods and single-crystal X-ray diffraction analyses. The nature
      and formation of complexes 1-3 were also examined by molecular orbital
      calculations using the B3LYP method of the density functional theory.

PMID- 16903731
TI  - Synthesis and coordination chemistry of a novel bidentate phosphine: 6
      (diphenylphosphino)-1,3,5-triaza-7-phosphaadamantane (PTA-PPh2).
AB  - The upper rim of 1,3,5-triaza-7-phosphaadamantane (PTA) has been modified for the
      first time. Lithiation of PTA, with n-butyllithium, resulted in deprotonation of
      an alpha-phosphorus methylene and the formation of 1,3,5-triaza-7
      phosphaadamantane-6-yllithium (PTA-Li). The chiral chelating phosphine 6
      (diphenylphosphino)-1,3,5-triaza-7-phosphaadamantane (PTA-PPh2) was synthesized,
      in racemic form, by the reaction of PTA-Li with ClPPh2. PTA-PPh2 has been fully
      characterized in solution by multinuclear NMR spectroscopy and mass spectrometry
      and in the solid state by X-ray crystallography. The 31P NMR spectrum contains a
      pair of doublets at -19.8 and -100.1 ppm (d, (2)J(PP) = 65 Hz). Unlike PTA, the
      new bidentate phosphine, PTA-PPh2, is insoluble in aqueous solutions. Two group 6
      metal carbonyl complexes, [M(CO)4(PTA-PPh2)] (M = W and Mo), were synthesized by
      the addition of PTA-PPh2 to cis-[M(CO)4(pip)2] and characterized by NMR
      spectroscopy, IR spectroscopy, and X-ray crystallography. Also reported are the
      solid-state structures of cis-[W(CO)4PTA2], cis-[W(CO)4(PTA)(PPh3)], and
      [W(CO)4DPPM] (DPPM = diphenylphosphinomethane). PTA-PPh2 appears to be sterically
      similar to and slightly more electron-donating than DPPM.

PMID- 16903732
TI  - 2D LnIII RuIII 2 compounds constructed from trans-[Ru(acac)2(CN)2]-. Syntheses,
      structures, and magnetic properties.
AB  - A series of cyano-bridged Ln(III)Ru(III)2 coordination polymers,
      Ph4P{Ln(NO3)2[Ru(acac)2(CN)2]2} [Ln = Tb (1), Dy (2), Er (3), Gd (4); Hacac =
      acetylacetone] have been synthesized by the reaction of Ln(NO3)3 with trans
      Ph4P[Ru(acac)2(CN)2] in methanol. X-ray crystallographic determination reveals
      that these compounds are isostructural and have a wavy (4,4) layer structure with
      the Ln3+ ions bridged by trans-[Ru(acac)2(CN)2]-. Magnetic studies shows that the
      magnetic coupling between the Ln(III) and Ru(III) ions through the cyano bridges
      in 1-4 is negligibly weak.

PMID- 16903733
TI  - Neutral molecular Pd6 hexagons using kappa3-P2O-terdentate ligands.
AB  - The one-step synthesis of three new P2O-terdentate carboxylic acid ditertiary
      phosphines 2-{(Ph2PCH2)2N}-3-(X)C6H3CO2H (X = OCH3, L1; X = OH, L2) and 2
      {(Ph2PCH2)2N}-5-(OH)C6H3CO2H (L3) by a phosphorus-based Mannich condensation
      reaction using Ph2PCH2OH and the appropriate amine in CH3OH is reported.
      Compounds L1-L3 function as typical kappa2-P2-didentate ligands upon complexation
      to Pd(CH3)Cl(cod) (cod = cycloocta-1,5-diene), affording the neutral, mononuclear
      complexes Pd(CH3)Cl(L1-L3) (1-3). Metathesis of 1 with NaX (X = Br, I) gave the
      corresponding (methyl)bromopalladium(II) (4) and (methyl)iodopalladium(II) (5)
      complexes, respectively. When chloroform or chloroform/methanol solutions of 1-3
      (or 5) were allowed to stand, at ambient temperatures, yellow crystalline solids
      were isolated in very high yields (71-88%) and were analyzed for the novel
      hexameric palladium(II) compounds 6-9. All new compounds reported have been fully
      characterized by a combination of spectroscopic (multinuclear NMR, Fourier
      transform IR, electrospray mass spectrometry, matrix-assisted laser desorption
      ionization time-of-flight mass spectrometry) and analytical methods. The self
      assembly reactions are remarkably clean as monitored by 31P{1H} and 1H NMR
      spectroscopy. Single-crystal X-ray structures have been determined for L1, 4,
      7.17CDCl3.2Et2O, 8.6CHCl3.8CH3OH, and 9.17CDCl3. In hexamers 7-9, all six square
      planar palladium(II) metal centers comprise a kappa2-P2-chelating diphosphine, a
      kappa1-O-monodentate carboxylate, and either a chloride or iodide ligand, leading
      to 48-membered metallomacrocycles (with outside diameters of ca. 2.5 nm). Whereas
      only intramolecular O-H...N hydrogen bonding between the hydroxy group and
      tertiary amine has been observed in 7, strong intermolecular O-H...O hydrogen
      bonding of the type CO...HO(CH3)...HO, involving a methanol solvate, has been
      found in 8, leading to an unprecedented three-dimensional network motif.

PMID- 16903734
TI  - The neglected Pt-N(sulfonamido) bond in Pt chemistry. New fluorophore-containing
      Pt(II) complexes useful for assessing Pt(II) interactions with biomolecules.
AB  - Treatment of cis-Pt(Me2SO)2Cl2 with DNSH-tren afforded [Pt(DNSH-tren)Cl]Cl and
      with DNSH-dienH, under increasingly more basic conditions, led to Pt(DNSH
      dienH)Cl(2), Pt(DNSH-dien)Cl, and Pt(DNS-dien). (DNSH = 5
      (dimethylamino)naphthalene-1-sulfonyl, linked via a sulfonamide group to tris(2
      aminoethyl)amine (DNSH-tren) and diethylenetriamine (DNSH-dienH); the H's in DNSH
      dienH designate protons sometimes lost upon Pt binding, i.e., sulfonamide NH for
      the dienH moiety and H8 for the DNSH moiety). Respectively, the three neutral
      DNSH-dienH-derived complexes are difunctional, monofunctional, and nonfunctional
      and exhibit decreasing fluorescence in this order as the dansyl group distance to
      Pt decreases. 2D NMR data establish that Pt(DNS-dien) has a Pt-C8 bond and a Pt
      N(sulfonamido) bond. Pt(DNSH-dien)Cl and [Pt(DNSH-tren)Cl]Cl bind to N7 of 6
      oxopurines (e.g., 5'-GMP, 3'-IMP, and 9-ethylguanine) and sulfur of methionine
      (met). Competition and challenge reactions for Pt(II) with met and 5'-GMP
      typically reveal that met binding is favored kinetically but that 5'-GMP binding
      is favored thermodynamically. This common type of behavior was found for [Pt(DNSH
      tren)Cl]Cl. In contrast, Pt(DNSH-dien)Cl had reduced kinetic selectivity for met.
      This unusual behavior undoubtedly arises as a consequence of the bound Pt
      N(sulfonamido) group, which donates strongly to Pt (as indicated by relatively
      upfield dien NH signals) and which places the bulky DNSH moiety close to the
      monofunctional reaction site. The decrease in the relatively upfield shifts of
      the DNSH group signals indicates that this group stacks with the purine. This
      stacking could explain the unprecedented, relatively low reactivity of a Pt
      complex bearing a dien-type ligand toward met vs 5'-GMP.

PMID- 16903735
TI  - A family of [Mn6] complexes featuring tripodal ligands.
AB  - The synthesis and magnetic properties of four new Mn complexes containing
      tripodal alcohol ligands are reported: [Mn6(OAc)6(H2tea)2(tmp)2].2MeCN (1.2MeCN),
      [Mn6(acac)4(OAc)2(Htmp)2(H2N-ep)2] (2), [Mn6(OAc)8(tmp)2(py)4].2py (3.2py), and
      [Mn6(OAc)8(thme)2(py)4].2py (4.2py) [H3tea, triethanolamine; H3tmp, 1,1,1
      tris(hydroxymethyl)propane; H2N-H2ep, 2-amino-2-ethyl-1,3-propanediol; H3thme,
      1,1,1-tris(hydroxymethyl)ethane]. All complexes are mixed-valent with a
      [Mn(III)2Mn(II)4] oxidation assignment and are constructed from four edge-sharing
      triangles but differ slightly in that complexes 1 and 2 display a
      [Mn(III)2Mn(II)4(mu2-OR)6(mu3-OR)4]4+ core, while complexes 3 and 4 feature
      [Mn(III)2Mn(II)4(mu2-OR)2(mu3-OR)4]8+ and [Mn(III)2Mn(II)4(mu2-OR)4(mu3-OR)4]6+
      cores, respectively. dc and ac magnetic susceptibility studies in the 2-300 K
      range for complexes 1-4 reveal the presence of dominant antiferromagnetic
      exchange interactions, leading to ground states of S = 0 for 1 and 2, while
      complexes 3 and 4 display S = 4 ground states with D = -0.44 and -0.58 cm(-1),
      respectively. Single-molecule magnetism behavior was confirmed for 3 and 4 by the
      presence of sweep-rate and temperature-dependent hysteresis loops in single
      crystal M vs H studies at temperatures down to 40 mK. Theoretical density
      functional calculations were used to evaluate the individual pairwise exchange
      interactions present, confirming the diamagnetic ground states for 1 and 2 and
      the S = 4 ground states for 3 and 4.

PMID- 16903736
TI  - Ligand-promoted solvent-dependent ionization and conformational equilibria of
      Re(CO)3Br[CH2(S-tim)2] (tim = 1-methylthioimidazolyl). Crystal structures of
      Re(CO)3Br[CH2(S-tim)2] and {Re(CO)3(CH3CN)[CH2(S-tim)2]}(PF6).
AB  - The compounds Re(CO)3Br[CH2(S-tim)2] (1) and {Re(CO)3(CH3CN)[CH2(S-tim)2]}(PF6)
      (2), where tim is 1-methylthioimidazolyl, were prepared in high yields and
      characterized both in the solid state and in solution. The solid-state structures
      show that the ligand acts in a chelating binding mode where the eight-member
      chelate ring adopts twist-boat conformations in both compounds. A comparison of
      both solid-state IR data for CO stretching frequencies and the solution-phase
      voltammetric measurements for the Re(1+/2+) couples between 1, 2, and related N,N
      chelates of the rhenium tricarbonyl moiety indicate that the CH2(S-tim)2 ligand
      is a stronger donor than even the ubiquitous dipyridyl ligands. A combination of
      NMR spectroscopic studies and voltammetric studies revealed that compound 1
      undergoes spontaneous ionization to form {Re(CO)3(CH3CN)[CH2(S-tim)2]+}(Br-) in
      acetonitrile. Ionization does not occur in solvents such as CH2Cl2 or acetone
      that are less polar and Lewis basic (less coordinating). The equilibrium constant
      at 293 K for the ionization of 1 in CH3CN is 4.3 x 10(-3). The eight-member
      chelate rings in each 1 and 2 were found to be conformationally flexible in all
      solvents, and boat-chair conformers could be identified. Variable-temperature NMR
      spectroscopic studies were used to elucidate the various kinetic and
      thermodynamic parameters associated with the energetically accessible twist-boat
      to twist-boat and twist-boat to boat-chair interconversions.

PMID- 16903737
TI  - Palladium complexes of a phosphorus ylide with two stabilizing groups: synthesis,
      structure, and DFT study of the bonding modes.
AB  - The phosphorus ylide ligand [Ph3P=C(CO2Me)C(=NPh)CO2Me] (L1) has been prepared
      and fully characterized by spectroscopic, crystallographic, and density
      functional theory (DFT) methods (B3LYP level). The reactivity of L1 toward
      several cationic Pd(II) and Pt(II) precursors, with two vacant coordination
      sites, has been studied. The reaction of [M(C/?X)(THF)2]ClO4 with L1 (1:1 molar
      ratio) gives [M(C/?X)(L1)]ClO4 [M = Pd, C/?X = C6H4CH2NMe2 (1), S-C6H4C(H)MeNMe2
      (2), CH2-8-C9H6N (3), C6H4-2-NC5H4 (4), o-CH2C6H4P(o-tol)2 (6), eta3-C3H5 (7); M
      = Pt, C/?X = o-CH2C6H4P(o-tol)2 (5); M(C/?X) = Pd(C6F5)(SC4H8) (8), PdCl2 (9)].
      In complexes 1-9, the ligand L1 bonds systematically to the metal center through
      the iminic N and the carbonyl O of the stabilizing CO2Me group, as is evident
      from the NMR data and from the X-ray structure of 3. Ligand L1 can also be
      orthopalladated by reaction with Pd(OAc)2 and LiCl, giving the dinuclear
      derivative [Pd(mu-Cl)(C6H4-2-PPh2=C(CO2Me)C(CO2Me)=NPh)]2 (10). The X-ray crystal
      structure of 10 is also reported. In none of the prepared complexes 1-10 was the
      C(alpha) atom found to be bonded to the metal center. DFT calculations and Bader
      analysis were performed on ylide L1 and complex 9 and its congeners in order to
      assess the preference of the six-membered N,O metallacycle over the four-membered
      C,N and five-membered C,O rings. The presence of two stabilizing groups at the
      ylidic C causes a reduction of its bonding capabilities. The increasing strength
      of the Pd-C, Pd-O, and Pd-N bonds along with other subtle effects are responsible
      for the relative stabilities of the different bonding modes.

PMID- 16903738
TI  - 13C and 15N NMR studies of iron-bound cyanides of heme proteins and related model
      complexes: sensitive probe for detecting hydrogen-bonding interactions at the
      proximal and distal sides.
AB  - Studies of the 13C and 15N NMR paramagnetic shifts of the iron-bound cyanides in
      the ferric cyanide forms of various heme proteins containing the proximal
      histidine and related model complexes are reported. The paramagnetic shifts of
      the 13C and 15N NMR signals of the iron-bound cyanide are not significantly
      affected by the substitution of the porphyrin side chains. On the other hand, the
      paramagnetic shifts of both the 13C and 15N NMR signals decrease with an increase
      in the donor effect of the proximal ligand, and the 13C NMR signal is more
      sensitive to a modification of the donor effect of the proximal ligand than the
      15N NMR signal. With the tilt of the iron-imidazole bond, the paramagnetic shift
      of the 13C NMR signal increases, whereas that of the 15N NMR signal decreases.
      The hydrogen-bonding interaction of the iron-bound cyanide with a solvent
      decreases the paramagnetic shift of both 13C and 15N NMR signals, and the effect
      is more pronounced for the 15N NMR signal. Data on the 13C and 15N NMR signals of
      iron-bound cyanide for various heme proteins are also reported and analyzed in
      detail. Substantial differences in the 13C and 15N NMR shifts for the heme
      proteins can be explained on the basis of the results for the model complexes and
      structures around the heme in the heme proteins. The findings herein show that
      the paramagnetic shift of the 13C NMR signal of the iron-bound cyanide is a good
      probe to estimate the donor effect of the proximal imidazole and that the ratio
      of 15N/13C NMR shifts allows the hydrogen-bonding interaction on the distal side
      to be estimated.

PMID- 16903739
TI  - On the paucity of molecular actinide complexes with unsupported metal-metal
      bonds: a comparative investigation of the electronic structure and metal-metal
      bonding in U2X6 (X = Cl, F, OH, NH2, CH3) complexes and d-block analogues.
AB  - Density functional calculations have been performed on M2X6 complexes (where M =
      U, W, and Mo and X = Cl, F, OH, NH2, and CH3) to investigate general aspects of
      their electronic structures and explore the similarities and differences in metal
      metal bonding between f-block and d-block elements. A detailed analysis of the
      metal-metal interactions has been conducted using molecular orbital theory and
      energy decomposition methods. Multiple (sigma and pi) bonding is predicted for
      all species investigated, with predominant f-f and d-d metal orbital character,
      respectively, for U and W or Mo complexes. The energy decomposition analysis
      involves contributions from orbital interactions (mixing of occupied and
      unoccupied orbitals), electrostatic effects (Coulombic attraction and repulsion),
      and Pauli repulsion (associated with four-electron two-orbital interactions). The
      general results suggest that the overall metal-metal interaction is stronger in
      the Mo and W species, relative to the U analogues, as a consequence of a
      significantly less destabilizing contribution from the combined Pauli and
      electrostatic ("pre-relaxation") effects. Although the orbital-mixing ("post
      relaxation") contribution to the total bonding energy is predicted to have a
      larger magnitude in the U complexes, this is not sufficiently strong to
      compensate for the comparatively greater destabilization that originates from the
      Pauli-plus-electrostatic effects. Of the pre-relaxation terms, the Pauli
      repulsion is comparable in analogous U and d-block compounds, contrary to the
      electrostatic term, which is (much) less favorable in the U systems than in the W
      and Mo systems. This generally weak electrostatic stabilization accounts for the
      large pre-relaxation destabilization in the U complexes and, ultimately, for the
      relative weakness of the U-U bonds. The origin of the small electrostatic term in
      the U compounds is traced primarily to MX(3) fragment overlap effects.

PMID- 16903740
TI  - Ba4Ga2B8O18Cl2.NaCl: a new polar structure with NaCl inclusion.
AB  - The title compound, Ba4Ga2B8O18Cl2.NaCl, is found to crystallize in a polar space
      group P4(2)nm with cell dimensions of a = 12.1134(2) A and c = 6.8456(1) A. The
      basic building blocks of the structure are the B4O9 groups, which are
      interconnected by the GaO4 tetrahedron to form a three-dimensional net with Ba2+
      ion-, Cl- ion-, and NaCl molecule-filled tunnels. This net structure is closely
      related to that of mineral hilgardite, with which many variant compounds have
      been found. Both a powder second-harmonic-generation test and calculations
      suggest that it possesses an optical nonlinearity comparable to that of potassium
      dihydrogen phosphate.

PMID- 16903741
TI  - A novel ZnII-sensitive fluorescent chemosensor assembled within aminopropyl
      functionalized mesoporous SBA-15.
AB  - A novel Zn2+-sensitive fluorescent chemosensor SC/SBA-15 has been obtained by the
      self-assembly of 4-chloroaniline-N-salicylidene (SC), a Schiff base ligand,
      within the channel of silylation-modified SBA-15 without destroying its
      hexagonally ordered mesoporous structure. The remarkable 200-fold fluorescence
      enhancement with a large Stokes shift of 180 nm in luminescence emission upon the
      addition of Zn2+ is attributed to the formation of a coordinate complex of a
      large rigid conjugate system and Zn2+ ions.

PMID- 16903742
TI  - Optimizing small molecule activation and cleavage in three-coordinate M[N(R)Ar]3
      complexes.
AB  - The sterically hindered, three-coordinate metal systems M[N(R)Ar]3 (R = tBu, iPr;
      Ar = 3,5-C6H3Me2) are known to bind and activate a number of fundamental diatomic
      molecules via a [Ar(R)N]3M-L-L-M[N(R)Ar]3 dimer intermediate. To predict which
      metals are most suitable for activating and cleaving small molecules such as
      N(2), NO, CO, and CN(-), the M-L bond energies in the L-M(NH2)3 (L = O, N, C)
      model complexes were calculated for a wide range of metals, oxidation states, and
      dn (n = 2-6) configurations. The strongest M-O, M-N, and M-C bonds occurred for
      the d2, d3, and d4 metals, respectively, and for these d(n) configurations, the M
      C and M-O bonds were calculated to be stronger than the M-N bonds. For
      isoelectronic metals, the bond strengths were found to increase both down a group
      and to the left of a period. Both the calculated N-N bond lengths and activation
      barriers for N2 bond cleavage in the (H2N)3M-N-N-M(NH2)3 intermediate dimers were
      shown to follow the trends in the M-N bond energies. The three-coordinate
      complexes of Ta(II), W(III), and Nb(II) are predicted to deliver more favorable
      N2 cleavage reactions than the experimentally known Mo(III) system and the
      Re(III)Ta(III) dimer, [Ar(R)N]3Re-CO-Ta[N(R)Ar]3, is thermodynamically best
      suited for cleaving CO.

PMID- 16903743
TI  - Preparation and crystal structure of dual-functional precursor complex
      bis(acetylacetonato)nickel(II) with 4-pyridyltetrathiafulvalene.
AB  - A tetrathiafulvalene (TTF) derivative 4-pyridyltetrathiafulvalene (Py-TTF) was
      synthesized. The 1:2 Ni complex 1 of bis(acetylacetonato)nickel(II) coordinated
      with Py-TTF was prepared. Complex 1 crystallizes in the monoclinic space group
      P2(1)/c. Two pyridyl N atoms from two different molecules of Py-TTF are
      coordinated in the trans configuration to the Ni ion of Ni(acac)2 to form an
      octahedral Ni complex, which is a precursor for both conducting and magnetic
      materials.

PMID- 16903744
TI  - Phosphorus(I) iodide: a versatile metathesis reagent for the synthesis of low
      oxidation state phosphorus compounds.
AB  - An improved method for the synthesis of cyclic low oxidation state P cations is
      presented. The only byproducts of the reaction of phosphorus triiodide with
      chelating phosphines are readily removed, resulting in an easily accessible P(I)
      reagent with an anion that can be readily replaced through salt metathesis
      chemistry. These P(I) salts are surprisingly stable, even in O2 and moisture, and
      the origin of this unusual stability is elucidated using density functional
      theory calculations.

PMID- 16903745
TI  - Structural, redox, and photophysical studies of the tetra(pyridyl)porphyrin
      complex containing four (2,2'-bipyridine)(2,2':6',2"-terpyridine)ruthenium(II)
      groups.
AB  - New hybrid complexes of polypyridyl ruthenium and pyridylporphyrins have been
      prepared by the coordination of pyridyl nitrogens to the ruthenium centers. A 1:4
      hybrid complex, [{Ru(bpy)(trpy)}4(mu4-H2Py4P)]8+ ([1]8+) (bpy = 2,2'-bipyridine;
      trpy = 2,2':6',2"-terpyridine; H2Py4P = 5,10,15,20-tetra(4-pyridyl)porphyrin),
      has been characterized by the single-crystal X-ray diffraction method. A 1:1
      complex, [{Ru(bpy)(trpy)}(H2PyT3P)]2+ ([2]2+) (H2PyT3P = 5-(4
      pyridyl)tritolylporphyrin) has also been prepared. The Soret band of the
      porphyrin ring shifts to longer wavelength with some broadening, the extent of
      the shift being larger for [1]8+. Cyclic voltammograms of the two complexes show
      simple overlap of the component redox waves. The complexes are weakly emissive at
      room temperature, which becomes stronger at lower temperatures. While [1]8+ at
      >140 K and [2]2+ at 77-280 K show only porphyrin fluorescence, [1]8+ at <140 K
      shows ruthenium and porphyrin phosphorescence, in addition to the porphyrin
      fluorescence.

PMID- 16903746
TI  - Proton-induced luminescence of mono- and dinuclear rhenium(I) tricarbonyl
      complexes containing 4-pyridinealdazine.
AB  - New mono- and dinuclear rhenium(I) tricarbonyls, of formulas [Re(bpy)(CO)3(PCA)]+
      (1), [(bpy)(CO)3Re(I)(PCA)Re(I)(CO)3(bpy)]2+ (2), and
      [(bpy)(CO)3Re(I)(PCA)Ru(II)(NH3)5]3+ (3) (bpy = 2,2'-bipyridine, PCA = 4
      pyridinecarboxaldehydeazine), have been synthesized as PF6- salts and
      characterized by spectroscopic, electrochemical, and photophysical techniques.
      These species do not emit at room temperature in CH(3)CN; however, in aqueous
      solutions, a decrease in pH induces luminescence in all of them, due to
      protonation of one of the N atoms of the -C=N-N=C- chain of PCA, as indicated by
      the pKa values of the ground states, obtained by absorption measurements, which
      are ca. 3 orders of magnitude lower than the pKa value of the pyridine N of PCA
      in complex 1. On the other hand, the values of pKa* of the excited states,
      obtained by emission measurements, of complexes 1 and 2 are similar (pKa* = 2.7
      +/- 0.1 at I = 0.1 M) and higher than those of the corresponding ground states.
      At low values of pH, chemical decomposition takes place rapidly in complex 3, but
      not in 1 and 2, supporting the possible use of these latter species as
      luminescent sensors of pH. The heterodinuclear complex, of formula
      [(bpy)(CO)3Re(I)(PCA)Ru(III)(NH3)5]4+, was obtained by bromine oxidation of the
      [Re(I), Ru(II)] precursor in CH3CN solution; from spectral and electrochemical
      measurements, the recombination charge-transfer reaction [Re(II), Ru(II) ] -->
      [Re(I), Ru(III)], which occurs after photoexcitation, is predicted to lie in the
      Marcus inverted region.

PMID- 16903747
TI  - Reactivity of (ferrocenylmethyl)phosphine toward palladium and platinum
      chlorides. X-ray structure of [Pd(PH2CH2Fc)Cl(mu-PHCH2Fc)]4 (Fc = ferrocenyl), a
      unique complex containing a Pd4P4 cycle.
AB  - The reaction of 2 equiv of the air-stable primary phosphine
      (ferrocenylmethyl)phosphine (PH2CH2Fc, 1) with [Pd(cod)Cl2] (Fc = ferrocenyl; cod
      = 1,5-cyclooctadiene) at 298 K gave the phosphanido-bridged Pd(II) tetramer
      [Pd(PH2CH2Fc)Cl(mu-PHCH2Fc)]4 (2), which shows an unprecedented arrangement of
      four Pd atoms embedded in an eight-membered Pd4P4 ring. An X-ray diffraction
      study showed that 2 crystallizes in the triclinic space group P with a =
      17.607(7) A, b = 17.944(7) A, c = 18.792(7) A, alpha = 107.120(12) degrees, beta
      = 96.344(13) degrees, gamma = 117.087(15) degrees . Each molecule contains four
      palladium atoms in a distorted square-planar coordination formed by one chlorine
      and three phosphorus atoms. Two of the latter belong to bridging primary
      phosphanides and the remaining one is contributed by a terminal PH2CH2Fc ligand.
      The coordination environments of neighboring metal centers adopt an almost
      perpendicular mutual orientation. The reaction of 2 equiv of 1 with [Pt(cod)Cl2]
      at 323 K yielded the analogous Pt(II) tetramer of formula [Pt(PH2CH2Fc)Cl(mu
      PHCH2Fc)]4 (3), which was fully characterized by multinuclear and dynamic NMR,
      IR, and elemental analyses. Single-crystal X-ray diffraction on 3 confirmed the
      tetranuclear arrangement in the solid state, but orientational disorder of the
      molecule precludes a more detailed discussion of the structure. Low-temperature
      NMR experiments in CD2Cl2 showed the presence of two slowly interconnecting
      conformers. Reaction of 1 and [M(cod)Cl2] (M = Pd or Pt) at lower temperatures
      (273 K for Pd, 295 K for Pt) in dichloromethane allowed the detection in solution
      of the mononuclear species cis-[M(PH2CH2Fc)2Cl2] (M = Pd, 4; M = Pt, 5) which,
      upon heating, transformed into the tetramers 2 and 3, respectively. Solid samples
      of 4 and 5 could be isolated after workup at low temperature and were
      characterized by conventional spectroscopic methods.

PMID- 16903748
TI  - Cube-type nitrido complexes containing titanium and zinc/copper.
AB  - Several azaheterometallocubane complexes containing [MTi3N4] cores have been
      prepared by the reaction of [{Ti(eta5-C5Me5)(mu-NH)}3(mu3-N)] (1) with zinc(II)
      and copper(I) derivatives. The treatment of 1 with zinc dichloride in toluene at
      room temperature produces the adduct [Cl2Zn{(mu3-NH)3Ti3(eta5-C5Me5)3(mu3-N)}]
      (2). Attempts to crystallize 2 in dichloromethane gave yellow crystals of the
      ammonia adduct [(H3N)Cl2Zn{(mu3-NH)Ti3(eta5-C5Me5)3(mu-NH)2(mu3-N)}] (3). The
      analogous reaction of 1 with alkyl, (trimethylsilyl)cyclopentadienyl, or amido
      zinc complexes [ZnR2] leads to the cube-type derivatives [RZn{(mu3-N)(mu3
      NH)2Ti3(eta5-C5Me5)3(mu3-N)}] (R = CH2SiMe3 (5), CH2Ph (6), Me (7), C5H4SiMe3
      (8), N(SiMe3)2 (9)) via RH elimination. The amido complex 9 decomposes in the
      presence of ambient light to generate the alkyl derivative
      [{Me3Si(H)N(Me)2SiCH2}Zn{(mu3-N)(mu3-NH)2Ti3(eta5-C5Me5)3(mu3-N)}] (10). The
      chloride complex 2 reacts with lithium cyclopentadienyl or lithium indenyl
      reagents to give the cyclopentadienyl or indenyl zinc derivatives [RZn{(mu3
      N)(mu3-NH)2Ti3(eta5-C5Me5)3(mu3-N)}] (R = C5H5 (11), C9H7 (12)). Treatment of 1
      with copper(I) halides in toluene at room temperature leads to the adducts
      [XCu{(mu3-NH)3Ti3(eta5-C5Me5)3(mu3-N)}] (X = Cl (13), I (14)). Complex 13 reacts
      with lithium bis(trimethylsilyl)amido in toluene to give the precipitation of
      [{Cu(mu4-N)(mu3-NH)2Ti3(eta5-C5Me5)3(mu3-N)}2] (15). Complex 15 is prepared in a
      higher yield through the reaction of 1 with [{CuN(SiMe3)2}4] in toluene at 150
      degrees C. The addition of triphenylphosphane to 15 in toluene produces the
      single-cube compound [(Ph3P)Cu{(mu3-N)(mu3-NH)2Ti3(eta5-C5Me5)3(mu3-N)}] (16).
      The X-ray crystal structures of 3, 8, 9, and 15 have been determined.

PMID- 16903749
TI  - Coordination chemistry of the solvated AgI and AuI ions in liquid and aqueous
      ammonia, trialkyl and triphenyl phosphite, and tri-n-butylphosphine solutions.
AB  - The coordination chemistry of solvated Ag(I) and Au(I) ions has been studied in
      some of the most strong electron-pair donor solvents, liquid and aqueous ammonia,
      and the P donor solvents triethyl, tri-n-butyl, and triphenyl phosphite and tri-n
      butylphosphine. The solvated Ag(I) ions have been characterized in solution by
      means of extended X-ray absorption fine structure (EXAFS), Raman, and (107)Ag NMR
      spectroscopy and the solid solvates by means of thermogravimetry and EXAFS and
      Raman spectroscopy. The Ag(I) ion is two- and three-coordinated in aqueous and
      liquid ammonia solutions with mean Ag-N bond distances of 2.15(1) and 2.26(1) A,
      respectively. The crystal structure of [Ag(NH3)3]ClO4.0.47 NH3 (1) reveals a
      regular trigonal-coplanar coordination around the Ag(I) ion with Ag-N bond
      distances of 2.263(6) A and a Ag...Ag distance of 3.278(2) A separating the
      complexes. The decomposition products of 1 have been analyzed, and one of them,
      [Ag(NH3)2]ClO4, has been structurally characterized by means of EXAFS, showing
      [Ag(NH3)2] units connected into chains by double O bridges from perchlorate ions;
      the Ag...Ag distance is 3.01(1) A. The linear bisamminegold(I) complex,
      [Au(NH3)2]+, is predominant in both liquid and aqueous ammonia solutions, as well
      as in solid [Au(NH3)2]BF4, with Au-N bond distances of 2.022(5), 2.025(5), and
      2.026(7) A, respectively. The solvated Ag(I) ions are three-coordinated, most
      probably in triangular fashion, in the P donor solvents with mean Ag-P bond
      distances of 2.48-2.53 A. The Au(I) ions are three-coordinated in triethyl
      phosphite and tri-n-butylphosphine solutions with mean Au-P bond distances of
      2.37(1) and 2.40(1) A, respectively.

PMID- 16903750
TI  - Structure and magnetic properties of a non-heme diiron complex singly bridged by
      a hydroxo group.
AB  - The synthesis of the first singly bridged non-heme diiron complex with a mu
      hydroxo bridging ligand, [{(salten)Fe}2(OH)][B(C6H5)4].(CH3CN)x.(H2O)y (1)
      [H2salten = 4-azaheptane-1,7-bis(salicylideneiminate)], is reported. The complex
      has been characterized with X-ray crystallography, FTIR, magnetic susceptibility
      measurements, and Mossbauer spectroscopy. The data have been compared with the
      results of DFT calculations on both 1 and a model with an unsupported mu-oxo
      bridge (2) to verify the formulation of the complex as a mu-hydroxo-bridged
      species. The X-ray structure [Fe-O(H) = 1.997(1) A and Fe-O(H)-Fe = 159 degrees ]
      is consistent with the DFT-optimized geometry of 1 [Fe-O(H) = 2.02 A and Fe-O(H)
      Fe = 151 degrees ]; the Fe-O(H) distance in 1 is about 0.2 A longer than the Fe-O
      separations in the optimized geometry of 2 (1.84 A) and in the crystallographic
      structures of diiron(III) compounds with unsupported mu-oxo bridges (1.77-1.81
      A). The formulation of 1 as a hydroxo-bridged compound is also supported by the
      presence of an O-H stretch band in the FTIR spectrum of the complex. The magnetic
      susceptibility measurements of 1 reveal antiferromagnetic exchange (J = 42 cm(-1)
      and H(ex) = JS(1).S(2)). Nearly the same J value is obtained by analyzing the
      temperature dependence of the Mossbauer spectra (J = 43 cm(-1); other parameters:
      delta = 0.49 mm s(-1), DeltaE(Q) = -0.97 mm s(-1), and eta = 0.45 at 4.2 K). The
      experimental J values and Mossbauer parameters agree very well with those
      obtained from DFT calculations for the mu-hydroxo-bridged compound (J = 46 cm(
      1), delta = 0.48 mm s(-1), DeltaE(Q) = -1.09 mm s(-1), and eta = 0.35). The
      exchange coupling constant in 1 is distinctly different from the value J
      approximately 200 cm(-1) calculated for the optimized mu-oxo-bridged species, 2.
      The increased exchange-coupling in 2 arises primarily from a decrease in the Fe-O
      bond length.

PMID- 16903751
TI  - Tessellation of porphyrazines with porphyrins by design.
AB  - The efficient self-assembly and functional characterization of arrays containing
      multiple types of chromophores will provide a basis for the design and
      applications of functional photonic materials that are unobtainable using only
      one type of molecule. The design, synthesis, and characterization of
      supramolecular systems bearing two different types of porphyrinic chromophores,
      porphyrins and porphyrazines, are reported. Because the porphyrins and
      porphyrazines bear different exocyclic ligands for self-assembly by metal ion
      coordination, these systems require new supramolecular synthetic strategies
      wherein reactants are added in a specific order. These arrays display unique
      photophysical properties derived from the component chromophores, the metal
      geometry, and the supramolecular nanoarchitecture.

PMID- 16903752
TI  - NO* release from MbFe(II)NO and HbFe(II)NO after oxidation by peroxynitrite.
AB  - In this work, we showed that the reaction of peroxynitrite with MbFe(II)NO, in
      analogy to the corresponding reaction with HbFe(II)NO (Herold, S. Inorg. Chem.
      2004, 43, 3783-3785), proceeds in two steps via the formation of MbFe(III)NO,
      from which NO* dissociates to produce iron(III)myoglobin (Mb = myoglobin; Hb =
      hemoglobin). The second-order rate constants for the first steps are on the order
      of 10(4) and 10(3) M(-1) s(-1), for the reaction of peroxynitrite with MbFe(II)NO
      and HbFe(II)NO, respectively. For both proteins, we found that the values of the
      second-order rate constants increase with decreasing pH, an observation that
      suggests that HOONO is the species responsible for oxidation of the iron center.
      Nevertheless, it cannot be excluded that the pH-dependence arises from different
      conformations taken up by the proteins at different pH values. In the presence of
      1.2 mM CO2, the values of the second-order rate constants are larger, on the
      order of 10(5) and 10(4) M(-1) s(-1), for the reaction of peroxynitrite with
      MbFe(II)NO and HbFe(II)NO, respectively. The pH-dependence of the values for the
      reaction with MbFe(II)NO suggests that ONOOCO2- or the radicals produced from its
      decay (CO3*-/NO2*) are responsible for the oxidation of MbFe(II)NO to
      MbFe(III)NO. In the presence of large amounts of nitrite (in the tens and
      hundreds of millimoles range), we observed a slight acceleration of the rate of
      oxidation of HbFe(II)NO by peroxynitrite. A catalytic rate constant of 40 +/- 2
      M(-1) s(-1) was determined at pH 7.0. Preliminary studies of the reaction between
      nitrite and HbFe(II)NO showed that this compound also can oxidize the iron
      center, albeit at a significantly slower rate. At pH 7.0, we obtained an
      approximate second-order rate constant of 3 x 10(-3) M(-1) s(-1).

PMID- 16903753
TI  - Solvent-controlled synthesis and electrochemical lithium storage of one
      dimensional TiO2 nanostructures.
AB  - In this paper, one-dimensional (1-D) nanostructured TiO2 of different
      morphologies and structures have been selectively synthesized via a convenient,
      low-temperature solvothermal route and following calcination. Transmission
      electron microscopy, selected area electron diffraction, X-ray diffraction, and
      Brunauer-Emmett-Teller methods were used to characterize the morphology,
      crystalline structure, and specific surface area of these nanostructured TiO2.
      The formation of different morphologies, including nanowires and nanotubes, was
      achieved through a deliberate control of the cosolvent. In addition to the
      solvent-controlled procedures, another important feature of the synthesis in the
      present study was that either single-crystalline nanowires (TiO2-B) or
      polycrystalline nanotubes (anatase and TiO2-B) were achieved by heat treatment at
      350 degrees C. The electrochemical performances of the nanowires and nanotubes
      were further explored in terms of their potential application as anode materials
      for lithium-ion batteries. The lithium-insertion reactions involved in the two
      materials were elucidated by means of a galvanostatic method, cyclic voltammetry,
      and electrochemical impedance spectroscopy. The results suggest that both the
      crystalline structure and the unique 1-D morphology might be responsible for
      their favorable electrochemical properties. This work will be valuable for the
      understanding of the formation of nanostructured TiO2 by the wet-chemistry
      process and further applications.

PMID- 16903754
TI  - Jorgensen complex within a molecular container: selective encapsulation of trans
      [Co(en)2Cl2]+ into cucurbit[8]uril and influence of inclusion on guest's
      properties.
AB  - The unprecedented selective encapsulation of trans-[Co(en)2Cl2]+ from the mixture
      of trans and cis isomers into the cavity of macrocyclic cavitand cucurbit[8]uril
      (C48H48N32O16, CB[8]) leads to the inclusion compound {trans
      [Co(en)2Cl2]@CB[8]}Cl.17H2O (1). Single-crystal X-ray analysis, 1H NMR, and ESI
      MS spectra confirm the formation of host-guest complex 1 in both solid state and
      solution. The geometry of the complex cation alters significantly upon inclusion,
      which causes appreciable hypsochromic shifts of the absorption bands of the guest
      complex. According to TGA data, inclusion of trans-[Co(en)2Cl2]+ dramatically
      stabilizes the complex toward thermal decomposition. Encapsulation of trans
      [Co(en)2Cl2]+ into the CB[8] cavity also increases the stability of the metal
      complex toward isomerization into the cis form. The supramolecular adduct {cis
      [Co(en)2(H2O)2](CB[8])6}Cl3.ca109.5H2O (2) was isolated only after prolonged
      heating of an aqueous solution of 1 at 120 degrees C in an evacuated tube; it was
      characterized by X-ray crystallography, IR, and elemental analysis.

PMID- 16903755
TI  - Chemical bonding in phosphane and amine complexes of main group elements and
      transition metals.
AB  - The geometries and bond dissociation energies of the main group complexes X3B
      NX3, X3B-PX3, X3Al-NX3, and X3Al-PX3 (X = H, Me, Cl) and the transition metal
      complexes (CO)5M-NX3 and (CO)5M-PX3 (M = Cr, Mo, W) have been calculated using
      gradient-corrected density functional theory at the BP86/TZ2P level. The nature
      of the donor-acceptor bonds was investigated with an energy decomposition
      analysis. It is found that the bond dissociation energy is not a good measure for
      the intrinsic strength of Lewis acidity and basicity because the preparation
      energies of the fragments may significantly change the trend of the bond
      strength. The interaction energies between the frozen fragments of the borane
      complexes are in most cases larger than the interaction energies of the alane
      complexes. The bond dissociation energy of the alane complexes is sometimes
      higher than that of the borane analogues because the energy for distorting the
      planar equilibrium geometry of BX3 to the pyramidal from in the complexes is
      higher than for AlX3. Inspection of the three energy terms, DeltaE(Pauli),
      DeltaE(orb), and DeltaE(elstat), shows that all three of them must be considered
      to understand the trends of the Lewis acid and base strength. The orbital term of
      the donor-acceptor bonds with the Lewis bases NCl3 and PCl3 have a higher pi
      character than the bonds of EH3 and EMe3, but NCl3 and PCl3 are weaker Lewis
      bases because the lone-pair orbital at the donor atoms N and P has a high percent
      s character. The calculated DeltaE(int) values suggest that the trends of the
      intrinsic Lewis bases' strengths in the main-group complexes with BX3 and AlX3
      are NMe3 > NH3 > NCl3 and PMe3 > PH3 > PCl3. The transition metal complexes
      exhibit a somewhat different order with NH3 > NMe3 > NCl3 and PMe3 > PH3 > PCl3.
      The slightly weaker bonding of NMe3 than that of NH3 comes from stronger Pauli
      repulsion. The bond length does not always correlate with the bond dissociation
      energy, nor does it always correlate with the intrinsic interaction energy.

PMID- 16903756
TI  - M-P versus M=M bonds as protonation sites in the organophosphide-bridged
      complexes [M2Cp2(mu-PR2)(mu-PR'2)(CO)2], (M = Mo, W; R, R' = Ph, Et, Cy).
AB  - The unsaturated complexes [W2Cp2(mu-PR2)(mu-PR'2)(CO)2] (Cp = eta5-C5H5; R = R' =
      Ph, Et; R = Et, R' = Ph) react with HBF4.OEt2 at 243 K in dichloromethane
      solution to give the corresponding complexes [W2Cp2(H)(mu-PR2)(mu-PR'2)(CO)2]BF4,
      which contain a terminal hydride ligand. The latter rearrange at room temperature
      to give [W2Cp2(mu-H)(mu-PR2)(mu-PR'2)(CO)2]BF4, which display a bridging hydride
      and carbonyl ligands arranged parallel to each other (W-W = 2.7589(8) A when R =
      R' = Ph). This explains why the removal of a proton from the latter gives first
      the unstable isomer cis-[W2Cp2(mu-PPh2)2(CO)2]. The molybdenum complex [Mo2Cp2(mu
      PPh2)2(CO)2] behaves similarly, and thus the thermally unstable new complexes
      [Mo2Cp2(H)(mu-PPh2)2(CO)2]BF4 and cis-[Mo2Cp2(mu-PPh2)2(CO)2] could be
      characterized. In contrast, related dimolybdenum complexes having electron-rich
      phosphide ligands behave differently. Thus, the complexes [Mo2Cp2(mu-PR2)2(CO)2]
      (R = Cy, Et) react with HBF4.OEt2 to give first the agostic type phosphine
      bridged complexes [Mo2Cp2(mu-PR2)(mu-kappa2-HPR2)(CO)2]BF4 (Mo-Mo = 2.748(4) A
      for R = Cy). These complexes experience intramolecular exchange of the agostic H
      atom between the two inequivalent P positions and at room-temperature reach a
      proton-catalyzed equilibrium with their hydride-bridged tautomers [ratio
      agostic/hydride = 10 (R = Cy), 30 (R = Et)]. The mixed-phosphide complex
      [Mo2Cp2(mu-PCy2)(mu-PPh2)(CO)2] behaves similarly, except that protonation now
      occurs specifically at the dicyclohexylphosphide ligand [ratio agostic/hydride =
      0.5]. The reaction of the agostic complex [Mo2Cp2(mu-PCy2)(mu-kappa2
      HPCy2)(CO)2]BF4 with CN(t)Bu gave mono- or disubstituted hydride derivatives
      [Mo2Cp2(mu-H)(mu-PCy2)2(CO)2-x(CNtBu)x]BF4 (Mo-Mo = 2.7901(7) A for x = 1). The
      photochemical removal of a CO ligand from the agostic complex also gives a
      hydride derivative, the triply bonded complex [Mo2Cp2(H)(mu-PCy2)2(CO)]BF4 (Mo-Mo
      = 2.537(2) A). Protonation of [Mo2Cp2(mu-PCy2)2(mu-CO)] gives the hydroxycarbyne
      derivative [Mo2Cp2(mu-COH)(mu-PCy2)2]BF4, which does not transform into its
      hydride isomer.

PMID- 16903758
TI  - A rare mu-hydroxo-bridged species. synthesis, structure, and properties of mu
      hydroxo(tetraphenylporphyrinatomanganese(III))(phthalocyaninato(azido)chromium(II
      )), [(TPP)Mn-O(H)-CrPc(N3)].
AB  - A novel ditetrapyrrolic, heteroleptic, and heterometallic (Mn-Cr) mu-hydroxo
      bridged complex has been prepared, and its structural and general properties have
      been studied. The species mu
      hydroxo(tetraphenylporphyrinatomanganese(III))(phthalocyaninato(azido)chromium(II
      )), [(TPP)Mn-O(H)-CrPc(N3)], isolated as a chloronaphthalene (ClNP) solvate, has
      been structurally characterized by single-crystal X-ray work. The two (TPP)Mn and
      CrPc(N3) fragments are held together by the bridging mu-hydroxo ion with long Mn
      O [1.993(5) A] and Cr-O [1.976(5) A] bond distances and a Mn-O(H)-Cr angle of
      163.7(3) degrees . The five-coordinate Mn center in the (TPP)Mn fragment is
      displaced from the TPP rigorously planar central N4 core by 0.128 A, and the
      environment is typical of a Mn(III) high-spin site. The six-coordinate Cr(III) in
      the CrPc(N3) moiety lies practically in the plane of the phthalocyanine
      macrocycle (displacement toward the azido group: 0.054 A). The average Mn-N(pyr)
      and Cr-N(pyr) bond distances are 2.011(6) and 1.982(6) A, respectively, and the
      Mn-Cr bond distance is 3.929(2) A. The porphyrin and phthalocyanine rings are in
      an almost eclipsed position [5.16(2) degrees ], and the mean planes of the two
      macrocycles form a dihedral angle of 5.79(4) degrees. Crystal data for [(TPP)Mn
      O(H)-CrPc(N3)].2ClNP, C76H45CrMnN15O.2C10H7Cl: a = 16.645(3) A, b = 17.692(4) A,
      c = 25.828(5) A, alpha = 90 degrees , beta = 98.79(3) degrees , gamma = 90
      degrees , space group P2(1)/c (No. 14), V = 7517(3) A(3), Z = 4, R1 = 0.086, and
      wR2 = 0.267. IR and UV-vis-near-IR spectral and room temperature magnetic
      susceptibility data of the [Mn-Cr] species are also presented.

PMID- 16903757
TI  - Glucosamine conjugates of tricarbonylcyclopentadienyl rhenium(I) and
      technetium(I) cores.
AB  - To obtain a 99mTc glucose conjugate for imaging, double-ligand transfer (DLT) and
      related reactions were examined for the preparation of CpM(CO)3 (Cp =
      cyclopentadienyl; M = Re, Tc) complexes with pendant carbohydrates at Cp.
      Tricarbonyl{N-(1,3,4,6-tetra-O-acetyl-2-amino-2-deoxy-beta-D
      glucopyranose)cyclopentadienyl carboxamide}rhenium(I) (1a) and tricarbonyl{N-(2
      amino-2-deoxy-beta-D-glucopyranose)cyclopentadienyl carboxamide}rhenium(I) (2a)
      were prepared. The compounds were fully characterized by mass spectrometry,
      elemental analysis, IR, and NMR spectroscopy. Full assignment of the NMR spectra
      verified the pendant nature of the glucosamine moieties in the solution state and
      that 2a exists as both anomers. The solid-state structure of 2a was determined by
      X-ray crystallography, again confirming the pendant nature of the glucosamine,
      but differing from the solution state in that the beta anomer crystallized
      preferentially (93%). Compound 2a was determined to be a high-affinity
      competitive inhibitor (Ki = 330 +/- 70 microM) of the glucose metabolism enzyme
      hexokinase, demonstrating that it retains certain biological activity. The 99mTc
      analogues 1b and 2b were prepared in moderate radiochemical yields by means of
      the single-ligand transfer (SLT) route, which is more pertinent to
      radiopharmaceutical synthesis.

PMID- 16903759
TI  - Which nido:nido-macropolyhedral boranes are most stable?
AB  - A comparison of the relative stabilities computed at RB3LYP/6
      311+G(d,p)//RB3LYP/6-31G(d)+ZPE of the neutral nido-single clusters and two
      vertex-sharing macropolyhedral nido:nido-clusters shows single-cluster nido
      boranes with up to 11 vertexes to be energetically more favorable than isomeric
      macropolyhedral boranes. Extra hydrogen atoms at the open face have a significant
      influence on the relative stabilities of the single cluster nido-boranes vs
      nido:nido-macropolyhedral boranes. For anionic species, a clear-cut turning point
      for macropolyhedral preference is shifted to no less than 17 vertexes.
      Thermodynamically most stable neutral and anionic nido:nido-macropolyhedral
      boranes usually consist of a nido-10-vertex and a nido-11-vertex unit,
      respectively. The relative stabilities of isomeric neutral macropolyhedra reflect
      the patterns exhibited by the sum of thermodynamic stabilities of the individual
      clusters.

PMID- 16903760
TI  - Observation of internal electron transfer in bulky allyl ytterbium complexes with
      substituted terpyridine ligands.
AB  - A series of new bulky allyl terpyridyl-ytterbium complexes have been synthesized
      to determine the effect of allyl ligands on the internal charge-transfer process
      that exists in these materials. Compared to the pentamethylcyclopentadienyl
      ytterbocene compound Cp*2Yb(tpyCN) (nu(C(triple bond)N) = 2172 cm(-1)), the
      symmetrically substituted allyl complex [1,3-(SiMe3)2C3H3]2Yb(tpyCN) possesses a
      markedly lowered C(triple bond)N frequency of 2130 cm(-1). Furthermore, the
      electronic nature of these bulky allyl complexes can be tuned, as demonstrated by
      the C(triple bond)N frequency of the asymmetric derivatives [1
      (SiMe3)C3H4]2Yb(tpyCN) and [1-(SiPh3)-3-(SiMe3)C3H3]2Yb(tpyCN) (2171 and 2164 cm(
      1), respectively). The differences in these frequencies can be attributed to
      differences in the ligands' steric and electronic character. Single-crystal X-ray
      characterization of [1,3-(SiMe3)2C3H3]2Yb(tpy) reveals that the allyl moiety
      possesses shorter Yb-C and Yb-N bond distances than the Cp* analogue. The
      magnetic susceptibility data for [1,3-(SiMe3)2C3H3]2Yb(tpy) departs dramatically
      from the Curie law, with a room-temperature magnetic moment of 2.95 mu(B).

PMID- 16903761
TI  - Roof-shaped halide-bridged bimetallic complexes via ring expansion reaction.
AB  - Binucleating behavior of rigid triptycene-based ligands has been studied. It has
      been demonstrated that trans-spanned transition-metal mononuclear complexes
      bearing 1,8-bis(diisopropylphosphino)triptycene (L1) and 1-diisopropylphosphino-8
      diphenylphosphinotriptycene (L2) react with an appropriate transition-metal
      precursor via a ring-expansion pathway to form unusual bimetallic quasi-closed
      structures. New palladium and rhodium complexes featuring strongly bent (ca. 115
      degrees ) M2(mu-Cl2) cores with very closely spanned metal centers (less than 3
      A) have been prepared using the described ring-expansion reaction and have been
      fully characterized. Despite a constrained arrangement of the binuclear system,
      halogen bridges in all new compounds were stable in both the solid state and
      solution showing no tendency for dissociation even in the presence of added Lewis
      bases. Spontaneous resolution of the dissymmetric Pd2(mu-Cl)2Cl2(1
      diisopropylphosphino-8-diphenylphosphinotriptycene) (2) into enantiopure
      antipodes is discussed as well.

PMID- 16903762
TI  - Rhenium-mediated coupling of acetonitrile and pyrazoles. New molecular clefts for
      anion binding.
AB  - The reaction of fac-[ReBr(CO)3(NCMe)2] (1) with either pyrazole (Hpz) or 3,5
      dimethylpyrazole (Hdmpz) in a 1:2 Re/pyrazole ratio affords the known complexes
      fac-[ReBr(CO)3(Hpz)2] (2) and [ReBr(CO)3(Hdmpz)2] (3). Using a 1:1 ratio, MeCN as
      solvent, and longer reaction times led to a mixture in which the major components
      are the pyrazolylamidino complexes fac-[ReBr(CO)3(HN=C(CH3)pz-kappa2N,N)] (4) and
      fac-[ReBr(CO)3(HN=C(CH3)dmpz-kappa2N,N)] (5). The complexes fac
      [ReBr(CO)3(Hpz)(NCMe)] (6) and fac-[ReBr(CO)3(Hdmpz)(NCMe)] (7) (along with 2 and
      3) were found to be minor components of these reactions. Analogous reactions of
      fac-[Re(OClO3)(CO)3(NCMe)2] yielded fac-[Re(NCCH3)(CO)3(HN=C(CH3)pz
      kappa2N,N)]ClO4 (8), fac-[Re(NCCH3)(CO)3(HN=C(CH3)dmpz-kappa2N,N)]ClO4 (9), fac
      [Re(Hpz)(CO)3(HN=C(CH3)pz-kappa2N,N)]ClO4 (10), and fac
      [Re(Hdmpz)(CO)3(HN=C(CH3)dmpz-kappa2N,N)]ClO4 (11). The X-ray structure of 11
      showed the perchlorate anion to be hydrogen-bonded by the N-H groups of the
      pyrazole and pyrazolylamidino ligands. The behavior of the compound fac
      [Re(Hdmpz)(CO)3(HN=C(CH3)dmpz-kappa2N,N)]BAr'4 (13) (synthesized by reaction of
      [ReBr(CO)3(Hdmpz)2] (3) with (i) AgOTf and (ii) NaBAr'(4)/MeCN) as an anion
      receptor has been studied in CD3CN solution. In addition, the structure of the
      supramolecular adduct fac-[Re(CO)3(Hdmpz)(HN=C(CH3)dmpz-kappa2N,N)].Cl (14),
      featuring chloride binding by the two N-H groups, was determined by X-ray
      diffraction.

PMID- 16903766
TI  - Botulinum toxin for the management of bladder dysfunction.
AB  - This review highlights a recent innovation in the medical treatment of detrusor
      overactivity (DO). Anticholinergics are usually the gold standard to treat
      bladder overactivity. Adverse effects and lack of efficacy are the two main
      causes for considering alternative treatments. Until recently, invasive surgery
      (mainly bladder augmentation) was the only available treatment option for
      patients with intractable DO. This article considers botulinum toxin type A (BTX
      A) injection as an alternative treatment to surgery in patients with DO who do
      not respond to anticholinergic therapy. To identify papers for inclusion in this
      review, we searched PubMed with the keywords 'botulinum toxin', 'overactive
      bladder', 'urinary incontinence' and 'neurogenic bladder' for the years 2000-5.
      Review articles were not included. Abstracts were cited only if they contained
      important new information. Experimental animal studies and articles or book
      chapters related to the use of botulinum toxin for other indications (such as
      achalasia and cervical dystonia) were analysed with regard to the mechanisms of
      action of botulinum toxin. From this review, it appears that BTX-A injection into
      the detrusor muscle is a very effective method for treating urinary incontinence
      secondary to neurogenic detrusor overactivity (NDO), as well as urinary
      incontinence due to idiopathic overactive bladder (IDO). In both conditions, the
      duration of effect seems to be at least 6 months. Overall success rates seem to
      be similar in both patient populations. For NDO, only one evidence-based medicine
      level 1 study is available, whereas for IDO, only evidence-based medicine level 3
      or 4 studies have been published. Particularly in this latter indication,
      injection technique and outcome parameters vary from study to study and need to
      be standardised. Without randomised controlled studies aimed at comparing
      different techniques and dosages, it remains difficult to decide what technique
      is optimal for treating patients with IDO who are not willing to perform clean
      intermittent self-catheterisation (CISC). Therefore, studies that compare
      different dosages and techniques with the risk of needing CISC in regard to the
      duration of the effect are mandatory. As more studies of repeated injections have
      been published, it appears that, at least at medium follow-up, the toxin remains
      as effective as after the first injection, and there is no evidence of change in
      bladder compliance or detrusor fibrosis. However, long-term observational studies
      are necessary to assess these last points. Finally, the commonly reported dose
      appears to be well tolerated, since few adverse effects have been reported.

PMID- 16903767
TI  - Early rheumatoid arthritis: pitfalls in diagnosis and review of recent clinical
      trials.
AB  - The treatment of rheumatoid arthritis (RA) has changed dramatically in the past
      decade as advancements in the understanding of the pathobiology of the disease
      have led to novel therapeutic agents. The recognition that early diagnosis and
      treatment leads to improvements in morbidity and mortality has altered the
      therapeutic strategy such that early therapy is now considered the standard of
      care. This review focuses on the challenges in making the diagnosis of early RA,
      including a broad differential diagnosis for inflammatory polyarthritis, poor
      performance of the standard classification criteria, difficulty in clinical
      assessment of synovitis, absence of absolute laboratory tests, inability of
      conventional radiography to detect bony changes early, and barriers to
      rheumatology care. Additionally, the pathogenesis of RA is highlighted, with
      particular emphasis on cytokine biology as it relates to therapeutic regimens.
      Relevant clinical trials in early RA are reviewed and discussed, including trials
      of combination disease-modifying antirheumatic drugs and biological therapy. The
      role of induction therapy as a novel therapeutic approach is highlighted. The
      search for predictors of response is reviewed and the external validity of the
      trials is analysed. Finally, the trials in early RA therapy suggest that swift
      intervention with combinations of medications is required for patients with
      severe RA. However, further research is needed to determine which regimen is
      appropriate for the individual patient with RA.

PMID- 16903768
TI  - Experience with remifentanil in neonates and infants.
AB  - Remifentanil is a relatively new synthetic opioid, which is not licensed
      worldwide for neonates and infants. Because of its unique pharmacokinetic
      properties with a short recovery profile, it could be the ideal opioid for
      neonates and infants, who are especially sensitive to respiratory depression by
      opioids. Therefore, we conducted a MEDLINE search on all articles dealing with
      the use of remifentanil in this important subgroup of patients. Most experience
      with remifentanil in neonates and infants is as maintenance anaesthesia during
      surgery. In approximately 300 neonates and infants, remifentanil proved to be an
      effective and safely used opioid for this indication. However, very limited data
      exist on remifentanil for analgesia and sedation of mechanically ventilated
      paediatric intensive care patients. Further research with remifentanil in
      neonates and infants should focus on this group of patients because remifentanil,
      with its very short context-sensitive half-life, could result in shorter
      extubation times compared with commonly used opioids such as morphine or
      fentanyl.

PMID- 16903769
TI  - Treating osteoporosis with bisphosphonates and addressing adherence: a review of
      oral ibandronate.
AB  - Osteoporosis is a common, chronic condition, affecting approximately half of all
      postmenopausal Caucasian women in the US. Vertebral fractures occur as a result
      of osteoporosis and lead to increased hospitalisation and mortality, and
      adversely affect patient quality of life. The burden of osteoporosis on
      healthcare systems is expected to rise as the elderly population continues to
      grow. Yet there are many medications for preventing and treating osteoporosis.
      Oral bisphosphonates are first-line treatment for osteoporosis, with demonstrated
      efficacy in increasing bone mineral density and reducing bone turnover, which
      reduces the incidence of fractures. However, adherence to medication is
      suboptimal, with approximately 40% of patients discontinuing treatment within 6
      months. Recent reports have suggested simplifying the dosage regimen as a
      strategy to help address this issue. Ibandronate is a potent, nitrogen-containing
      bisphosphonate which is administered once-monthly. Preclinical studies initially
      revealed the feasibility of extending the between-dose interval. Subsequent
      clinical studies have provided further evidence of the positive effects of
      extended-interval ibandronate administration in reducing the risk of vertebral
      fractures through increasing bone mineral density and reducing bone turnover
      without compromising bone quality. These studies have also demonstrated that
      ibandronate has a safety profile similar to placebo. Ibandronate has recently
      been approved for use in the US to treat postmenopausal osteoporosis. This review
      summarises the efficacy and safety of once-monthly oral ibandronate and discusses
      the implications of such a treatment in primary care in the US.

PMID- 16903770
TI  - Pharmacotherapy for overactive bladder: an evidence-based approach to selecting
      an antimuscarinic agent.
AB  - Multiple drugs are now available for the treatment of overactive bladder.
      Currently, the pharmacological approach is to deal with the problem at the
      neuromuscular junction by attempting to stop the activity of the neurotransmitter
      with antimuscarinic medications. This article reviews the positive and negative
      aspects of the agents that are currently available for use in the US. In
      randomised clinical trials, extended-release formulations of these agents appear
      as effective as the immediate-release formulations, but are associated with fewer
      adverse effects. Attempts to use entities that are muscarinic M(3) selective
      antimuscarinic agents have not significantly improved the efficacy, but have
      reduced the major adverse effect of excessively dry mouth. Dose escalation or
      titration is addressed to enhance efficacy further. None of these drugs appear to
      cause significant cardiac or CNS adverse events. This supports the continued use
      of these agents for overactive bladder symptomatology, as they appear to be
      effective in reducing symptoms and remain generally well tolerated.

PMID- 16903771
TI  - VSL#3 probiotic mixture: a review of its use in chronic inflammatory bowel
      diseases.
AB  - VSL#3 (VSL#3) is a high-concentration probiotic preparation of eight live freeze
      dried bacterial species that are normal components of the human gastrointestinal
      microflora, including four strains of lactobacilli (Lactobacillus casei, L.
      plantarum, L. acidophilus and L. delbrueckii subsp. bulgaricus), three strains of
      bifidobacteria (Bifidobacterium longum, B. breve and B. infantis) and
      Streptococcus salivarius subsp. thermophilus. Data from noncomparative trials
      suggest that VSL#3 has clinical potential in the treatment of active mild to
      moderate ulcerative colitis and as maintenance therapy for patients with
      ulcerative colitis in remission. In addition, a randomised, open-label,
      multicentre trial showed that VSL#3 in combination with low-dose balsalazide (a
      prodrug of mesalazine [mesalamine; 5-aminosalicylic acid]) was more effective
      than standard doses of basalazide or mesalazine monotherapy in the treatment of
      acute mild to moderate ulcerative colitis. Randomised, double-blind, placebo
      controlled studies have shown VSL#3 is effective in preventing the onset of acute
      pouchitis in patients with newly formed surgical pouches, and in maintaining
      remission following antibacterial treatment of acute pouchitis in patients with a
      history of refractory or recurrent pouchitis. Treatment guidelines from the US
      and the UK include VSL#3 as a therapeutic option for the prevention of pouchitis
      relapse in patients with chronic pouchitis. In general, VSL#3 was well tolerated
      in clinical trials. Large, well designed, controlled confirmatory clinical trials
      will further determine the place of VSL#3 in the treatment of ulcerative colitis.

PMID- 16903772
TI  - Nebivolol: a review of its use in the management of hypertension and chronic
      heart failure.
AB  - Nebivolol is a third-generation beta-adrenoceptor antagonist. It differs from
      other beta-adrenoceptor antagonists as it combines highly selective beta(1)
      adrenoceptor antagonist properties with nitric oxide-mediated vasodilatory
      actions and beneficial effects on endothelial function. Nebivolol is approved in
      Europe and several other countries for the treatment of essential hypertension
      and in Europe for the treatment of stable mild or moderate chronic heart failure
      (CHF) in addition to standard therapies in elderly patients aged >or=70 years.
      Nebivolol is an effective antihypertensive agent and is well tolerated in
      patients with hypertension. The drug also effectively decreased the composite
      endpoint of mortality and cardiovascular hospital admission in elderly patients
      with CHF and was generally well tolerated in this population. Nebivolol should be
      considered as an alternative first-line treatment option for patients with
      uncomplicated mild to moderate essential hypertension and in elderly patients
      with CHF.

PMID- 16903775
TI  - Health development versus medical relief: the illusion versus the irrelevance of
      sustainability.

PMID- 16903774
TI  - Mycobacterium tuberculosis induces interleukin-32 production through a caspase-
      1/IL-18/interferon-gamma-dependent mechanism.
AB  - BACKGROUND: Interleukin (IL)-32 is a newly described proinflammatory cytokine
      that seems likely to play a role in inflammation and host defense. Little is
      known about the regulation of IL-32 production by primary cells of the immune
      system. METHODS AND FINDINGS: In the present study, freshly obtained human
      peripheral blood mononuclear cells were stimulated with different Toll-like
      receptor (TLR) agonists, and gene expression and synthesis of IL-32 was
      determined. We demonstrate that the TLR4 agonist lipopolysaccharide induces
      moderate (4-fold) production of IL-32, whereas agonists of TLR2, TLR3, TLR5, or
      TLR9, each of which strongly induced tumor necrosis factor alpha and IL-6, did
      not stimulate IL-32 production. However, the greatest amount of IL-32 was induced
      by the mycobacteria Mycobacterium tuberculosis and M. bovis BCG (20-fold over
      unstimulated cells). IL-32-induced synthesis by either lipopolysaccharide or
      mycobacteria remains entirely cell-associated in monocytes; moreover, steady
      state mRNA levels are present in unstimulated monocytes without translation into
      IL-32 protein, similar to other cytokines lacking a signal peptide. IL-32
      production induced by M. tuberculosis is dependent on endogenous interferon-gamma
      (IFNgamma); endogenous IFNgamma is, in turn, dependent on M. tuberculosis-induced
      IL-18 via caspase-1. CONCLUSIONS: In conclusion, IL-32 is a cell-associated
      proinflammatory cytokine, which is specifically stimulated by mycobacteria
      through a caspase-1- and IL-18-dependent production of IFNgamma.

PMID- 16903776
TI  - IL-32: an emerging player in the immune response network against tuberculosis?

PMID- 16903777
TI  - Infectious diseases, climate influences, and nonstationarity.

PMID- 16903778
TI  - Climate cycles and forecasts of cutaneous leishmaniasis, a nonstationary vector
      borne disease.
AB  - BACKGROUND: Cutaneous leishmaniasis (CL) is one of the main emergent diseases in
      the Americas. As in other vector-transmitted diseases, its transmission is
      sensitive to the physical environment, but no study has addressed the
      nonstationary nature of such relationships or the interannual patterns of cycling
      of the disease. METHODS AND FINDINGS: We studied monthly data, spanning from 1991
      to 2001, of CL incidence in Costa Rica using several approaches for nonstationary
      time series analysis in order to ensure robustness in the description of CL's
      cycles. Interannual cycles of the disease and the association of these cycles to
      climate variables were described using frequency and time-frequency techniques
      for time series analysis. We fitted linear models to the data using climatic
      predictors, and tested forecasting accuracy for several intervals of time.
      Forecasts were evaluated using "out of fit" data (i.e., data not used to fit the
      models). We showed that CL has cycles of approximately 3 y that are coherent with
      those of temperature and El Nino Southern Oscillation indices (Sea Surface
      Temperature 4 and Multivariate ENSO Index). CONCLUSIONS: Linear models using
      temperature and MEI can predict satisfactorily CL incidence dynamics up to 12 mo
      ahead, with an accuracy that varies from 72% to 77% depending on prediction time.
      They clearly outperform simpler models with no climate predictors, a finding that
      further supports a dynamical link between the disease and climate.

PMID- 16903780
TI  - Which topical microbicides for blocking HIV-1 transmission will work in the real
      world?

PMID- 16903779
TI  - Macrophages inhibit neovascularization in a murine model of age-related macular
      degeneration.
AB  - BACKGROUND: Age-related macular degeneration (AMD) is the leading cause of
      blindness in people over 50 y of age in at least three continents. Choroidal
      neovascularization (CNV) is the process by which abnormal blood vessels develop
      underneath the retina. CNV develops in 10% of patients with AMD but accounts for
      up to 90% of the blindness from AMD. Although the precise etiology of CNV in AMD
      remains unknown, the macrophage component of the inflammatory response, which has
      been shown to promote tumor growth and support atherosclerotic plaque formation,
      is thought to stimulate aberrant angiogenesis in blinding eye diseases. The
      current theory is that macrophage infiltration promotes the development of
      neovascularization in CNV. METHODS AND FINDINGS: We examined the role of
      macrophages in a mouse model of CNV. IL-10(-/-) mice, which have increased
      inflammation in response to diverse stimuli, have significantly reduced CNV with
      increased macrophage infiltrates compared to wild type. Prevention of macrophage
      entry into the eye promoted neovascularization while direct injection of
      macrophages significantly inhibited CNV. Inhibition by macrophages was mediated
      by the TNF family death molecule Fas ligand (CD95-ligand). CONCLUSIONS: Immune
      vascular interactions can be highly complex. Normal macrophage function is
      critical in controlling pathologic neovascularization in the eye. IL-10 regulates
      macrophage activity in the eye and is an attractive therapeutic target in order
      to suppress or inhibit CNV in AMD that can otherwise lead to blindness.

PMID- 16903781
TI  - Is IL-10 a good target to inhibit choroidal neovascularisation in age-related
      macular disease?

PMID- 16903782
TI  - Local sharing as a predominant determinant of synaptic matrix molecular dynamics.
AB  - Recent studies suggest that central nervous system synapses can persist for
      weeks, months, perhaps lifetimes, yet little is known as to how synapses maintain
      their structural and functional characteristics for so long. As a step toward a
      better understanding of synaptic maintenance we examined the loss,
      redistribution, reincorporation, and replenishment dynamics of Synapsin I and
      ProSAP2/Shank3, prominent presynaptic and postsynaptic matrix molecules,
      respectively. Fluorescence recovery after photobleaching and photoactivation
      experiments revealed that both molecules are continuously lost from,
      redistributed among, and reincorporated into synaptic structures at time-scales
      of minutes to hours. Exchange rates were not affected by inhibiting protein
      synthesis or proteasome-mediated protein degradation, were accelerated by
      stimulation, and greatly exceeded rates of replenishment from somatic sources.
      These findings indicate that the dynamics of key synaptic matrix molecules may be
      dominated by local protein exchange and redistribution, whereas protein synthesis
      and degradation serve to maintain and regulate the sizes of local, shared pools
      of these proteins.

PMID- 16903783
TI  - Role of the AP2 beta-appendage hub in recruiting partners for clathrin-coated
      vesicle assembly.
AB  - Adaptor protein complex 2 alpha and beta-appendage domains act as hubs for the
      assembly of accessory protein networks involved in clathrin-coated vesicle
      formation. We identify a large repertoire of beta-appendage interactors by mass
      spectrometry. These interact with two distinct ligand interaction sites on the
      beta-appendage (the "top" and "side" sites) that bind motifs distinct from those
      previously identified on the alpha-appendage. We solved the structure of the beta
      appendage with a peptide from the accessory protein Eps15 bound to the side site
      and with a peptide from the accessory cargo adaptor beta-arrestin bound to the
      top site. We show that accessory proteins can bind simultaneously to multiple
      appendages, allowing these to cooperate in enhancing ligand avidities that appear
      to be irreversible in vitro. We now propose that clathrin, which interacts with
      the beta-appendage, achieves ligand displacement in vivo by self-polymerisation
      as the coated pit matures. This changes the interaction environment from liquid
      phase, affinity-driven interactions, to interactions driven by solid-phase
      stability ("matricity"). Accessory proteins that interact solely with the
      appendages are thereby displaced to areas of the coated pit where clathrin has
      not yet polymerised. However, proteins such as beta-arrestin (non-visual
      arrestin) and autosomal recessive hypercholesterolemia protein, which have direct
      clathrin interactions, will remain in the coated pits with their interacting
      receptors.

PMID- 16903784
TI  - The structural basis for promoter -35 element recognition by the group IV sigma
      factors.
AB  - The control of bacterial transcription initiation depends on a primary sigma
      factor for housekeeping functions, as well as alternative sigma factors that
      control regulons in response to environmental stresses. The largest and most
      diverse subgroup of alternative sigma factors, the group IV extracytoplasmic
      function sigma factors, directs the transcription of genes that regulate a wide
      variety of responses, including envelope stress and pathogenesis. We determined
      the 2.3-A resolution crystal structure of the -35 element recognition domain of a
      group IV sigma factor, Escherichia coli sigma(E)4, bound to its consensus -35
      element, GGAACTT. Despite similar function and secondary structure, the primary
      and group IV sigma factors recognize their -35 elements using distinct
      mechanisms. Conserved sequence elements of the sigma(E) -35 element induce a DNA
      geometry characteristic of AA/TT-tract DNA, including a rigid, straight double
      helical axis and a narrow minor groove. For this reason, the highly conserved AA
      in the middle of the GGAACTT motif is essential for -35 element recognition by
      sigma(E)4, despite the absence of direct protein-DNA interactions with these DNA
      bases. These principles of sigma(E)4/-35 element recognition can be applied to a
      wide range of other group IV sigma factors.

PMID- 16903793
TI  - An analysis of mutative sigma-self-adaptation on linear fitness functions.
AB  - This paper investigates sigma-self-adaptation for real valued evolutionary
      algorithms on linear fitness functions. We identify the step-size logarithm log
      sigma as a key quantity to understand strategy behavior. Knowing the bias of
      mutation, recombination, and selection on log sigma is sufficient to explain
      sigma-dynamics and strategy behavior in many cases, even from previously reported
      results on non-linear and/or noisy fitness functions. On a linear fitness
      function, if intermediate multi-recombination is applied on the object
      parameters, the i-th best and the i-th worst individual have the same sigma
      distribution. Consequently, the correlation between fitness and step-size sigma
      is zero. Assuming additionally that sigma-changes due to mutation and
      recombination are unbiased, then sigma-self-adaptation enlarges sigma if and only
      if mu < lambda/2, given (mu, lambda)-truncation selection. Experiments show the
      relevance of the given assumptions.

PMID- 16903785
TI  - A distributed chemosensory circuit for oxygen preference in C. elegans.
AB  - The nematode Caenorhabditis elegans has complex, naturally variable behavioral
      responses to environmental oxygen, food, and other animals. C. elegans detects
      oxygen through soluble guanylate cyclase homologs (sGCs) and responds to it
      differently depending on the activity of the neuropeptide receptor NPR-1: npr
      1(lf) and naturally isolated npr-1(215F) animals avoid high oxygen and aggregate
      in the presence of food; npr-1(215V) animals do not. We show here that hyperoxia
      avoidance integrates food with npr-1 activity through neuromodulation of a
      distributed oxygen-sensing network. Hyperoxia avoidance is stimulated by sGC
      expressing oxygen-sensing neurons, nociceptive neurons, and ADF sensory neurons.
      In npr-1(215V) animals, the switch from weak aerotaxis on food to strong
      aerotaxis in its absence requires close regulation of the neurotransmitter
      serotonin in the ADF neurons; high levels of ADF serotonin promote hyperoxia
      avoidance. In npr-1(lf) animals, food regulation is masked by increased activity
      of the oxygen-sensing neurons. Hyperoxia avoidance is also regulated by the
      neuronal TGF-beta homolog DAF-7, a secreted mediator of crowding and stress
      responses. DAF-7 inhibits serotonin synthesis in ADF, suggesting that ADF
      serotonin is a convergence point for regulation of hyperoxia avoidance.
      Coalitions of neurons that promote and repress hyperoxia avoidance generate a
      subtle and flexible response to environmental oxygen.

PMID- 16903794
TI  - A step forward in studying the compact genetic algorithm.
AB  - The compact Genetic Algorithm (cGA) is an Estimation of Distribution Algorithm
      that generates offspring population according to the estimated probabilistic
      model of the parent population instead of using traditional recombination and
      mutation operators. The cGA only needs a small amount of memory; therefore, it
      may be quite useful in memory-constrained applications. This paper introduces a
      theoretical framework for studying the cGA from the convergence point of view in
      which, we model the cGA by a Markov process and approximate its behavior using an
      Ordinary Differential Equation (ODE). Then, we prove that the corresponding ODE
      converges to local optima and stays there. Consequently, we conclude that the cGA
      will converge to the local optima of the function to be optimized.

PMID- 16903786
TI  - Timing the generation of distinct retinal cells by homeobox proteins.
AB  - The reason why different types of vertebrate nerve cells are generated in a
      particular sequence is still poorly understood. In the vertebrate retina,
      homeobox genes play a crucial role in establishing different cell identities.
      Here we provide evidence of a cellular clock that sequentially activates distinct
      homeobox genes in embryonic retinal cells, linking the identity of a retinal cell
      to its time of generation. By in situ expression analysis, we found that the
      three Xenopus homeobox genes Xotx5b, Xvsx1, and Xotx2 are initially transcribed
      but not translated in early retinal progenitors. Their translation requires cell
      cycle progression and is sequentially activated in photoreceptors (Xotx5b) and
      bipolar cells (Xvsx1 and Xotx2). Furthermore, by in vivo lipofection of "sensors"
      in which green fluorescent protein translation is under control of the 3'
      untranslated region (UTR), we found that the 3' UTRs of Xotx5b, Xvsx1, and Xotx2
      are sufficient to drive a spatiotemporal pattern of translation matching that of
      the corresponding proteins and consistent with the time of generation of
      photoreceptors (Xotx5b) and bipolar cells (Xvsx1 and Xotx2). The block of cell
      cycle progression of single early retinal progenitors impairs their
      differentiation as photoreceptors and bipolar cells, but is rescued by the
      lipofection of Xotx5b and Xvsx1 coding sequences, respectively. This is the first
      evidence to our knowledge that vertebrate homeobox proteins can work as effectors
      of a cellular clock to establish distinct cell identities.

PMID- 16903795
TI  - Optimum tracking with evolution strategies.
AB  - Evolutionary algorithms are frequently applied to dynamic optimization problems
      in which the objective varies with time. It is desirable to gain an improved
      understanding of the influence of different genetic operators and of the
      parameters of a strategy on its tracking performance. An approach that has proven
      useful in the past is to mathematically analyze the strategy's behavior in
      simple, idealized environments. The present paper investigates the performance of
      a multiparent evolution strategy that employs cumulative step length adaptation
      for an optimization task in which the target moves linearly with uniform speed.
      Scaling laws that quite accurately describe the behavior of the strategy and that
      greatly contribute to its understanding are derived. It is shown that in contrast
      to previously obtained results for a randomly moving target, cumulative step
      length adaptation fails to achieve optimal step lengths if the target moves in a
      linear fashion. Implications for the choice of population size parameters are
      discussed.

PMID- 16903796
TI  - A comparison of bloat control methods for genetic programming.
AB  - Genetic programming has highlighted the problem of bloat, the uncontrolled growth
      of the average size of an individual in the population. The most common approach
      to dealing with bloat in tree-based genetic programming individuals is to limit
      their maximal allowed depth. An alternative to depth limiting is to punish
      individuals in some way based on excess size, and our experiments have shown that
      the combination of depth limiting with such a punitive method is generally more
      effective than either alone. Which such combinations are most effective at
      reducing bloat? In this article we augment depth limiting with nine bloat control
      methods and compare them with one another. These methods are chosen from past
      literature and from techniques of our own devising. esting with four genetic
      programming problems, we identify where each bloat control method performs well
      on a per-problem basis, and under what settings various methods are effective
      independent of problem. We report on the results of these tests, and discover an
      unexpected winner in the cross-platform category.

PMID- 16903797
TI  - Automated global structure extraction for effective local building block
      processing in XCS.
AB  - Learning Classifier Systems (LCSs), such as the accuracy-based XCS, evolve
      distributed problem solutions represented by a population of rules. During
      evolution, features are specialized, propagated, and recombined to provide
      increasingly accurate subsolutions. Recently, it was shown that, as in
      conventional genetic algorithms (GAs), some problems require efficient processing
      of subsets of features to find problem solutions efficiently. In such problems,
      standard variation operators of genetic and evolutionary algorithms used in LCSs
      suffer from potential disruption of groups of interacting features, resulting in
      poor performance. This paper introduces efficient crossover operators to XCS by
      incorporating techniques derived from competent GAs: the extended compact GA
      (ECGA) and the Bayesian optimization algorithm (BOA). Instead of simple crossover
      operators such as uniform crossover or one-point crossover, ECGA or BOA-derived
      mechanisms are used to build a probabilistic model of the global population and
      to generate offspring classifiers locally using the model. Several offspring
      generation variations are introduced and evaluated. The results show that it is
      possible to achieve performance similar to runs with an informed crossover
      operator that is specifically designed to yield ideal problem-dependent
      exploration, exploiting provided problem structure information. Thus, we create
      the first competent LCSs, XCS/ECGA and XCS/BOA, that detect dependency structures
      online and propagate corresponding lower-level dependency structures effectively
      without any information about these structures given in advance.

PMID- 16903799
TI  - Schizophrenia: new pathological insights and therapies.
AB  - The neurodevelopmental hypothesis of schizophrenia posits an interaction between
      multiple susceptibility genes and one or more environmental insults in early
      life, resulting in altered brain development and the emergence of psychosis in
      early adulthood. Based on this framework, it has been argued that most
      neuropathological deficits observed in post mortem and neuroimaging studies of
      schizophrenia represent one or more lesions that originated in early life and
      remained static thereafter. However, recent longitudinal neuroimaging studies
      demonstrate a progressive component to the neuropathology of new-onset
      schizophrenia. This opens the possibility that the functional decline seen in
      many patients following the onset of illness may be halted or slowed. This review
      provides an update on developments in research on the neuropathology of
      schizophrenia and discusses recent advances in antipsychotic treatment and the
      potential impact on long-term outcomes.

PMID- 16903800
TI  - The close relationships of Lesbians and gay men.
AB  - This article reviews empirical studies of same-sex couples in the United States,
      highlighting consistent findings, drawing comparisons to heterosexual couples,
      and noting gaps in available research. U.S. Census data indicate that there were
      more than 600,000 same-sex couples living together in 2000. Research about
      relationship formation, the division of household labor, power, satisfaction,
      sexuality, conflict, commitment, and relationship stability is presented. Next,
      we highlight three recent research topics: the legalization of same-sex
      relationships through civil unions and same-sex marriage, the experiences of same
      sex couples raising children, and the impact of societal prejudice and
      discrimination on same-sex partners. We conclude with comments about the
      contributions of empirical research to debunking negative stereotypes of same-sex
      couples, testing the generalizability of theories about close relationships,
      informing our understanding of gender and close relationships, and providing a
      scientific basis for public policy.

PMID- 16903801
TI  - Visual object recognition: do we know more now than we did 20 years ago?
AB  - We review the progress made in the field of object recognition over the past two
      decades. Structural-description models, making their appearance in the early
      1980s, inspired a wealth of empirical research. Moving to the 1990s,
      psychophysical evidence for view-based accounts of recognition challenged some of
      the fundamental assumptions of structural-description theories. The 1990s also
      saw increased interest in the neurophysiological study of high-level visual
      cortex, the results of which provide some constraints on how objects may be
      represented. By 2000, neuroimaging arose as a viable means for connecting neurons
      to behavior. One of the most striking fMRI results has been category selectivity,
      which provided further constraints for models of object recognition. Despite this
      progress, the field is still faced with the challenge of developing a
      comprehensive theory that integrates this ever-increasing body of results and
      explains how we perceive and recognize objects.

PMID- 16903802
TI  - Perception of human motion.
AB  - Humans, being highly social creatures, rely heavily on the ability to perceive
      what others are doing and to infer from gestures and expressions what others may
      be intending to do. These perceptual skills are easily mastered by most, but not
      all, people, in large part because human action readily communicates intentions
      and feelings. In recent years, remarkable advances have been made in our
      understanding of the visual, motoric, and affective influences on perception of
      human action, as well as in the elucidation of the neural concomitants of
      perception of human action. This article reviews those advances and, where
      possible, draws links among those findings.

PMID- 16903803
TI  - The elaboration of personal construct psychology.
AB  - More than half a century has passed since the publication of George Kelly's
      (1955/1991) The Psychology of Personal Constructs. This review considers the
      elaboration of personal construct psychology (PCP) during this time, both by
      Kelly and by others who developed his ideas. Advances to the theory have
      principally concerned implicative relationships between constructs, construing of
      the self, social relationships, emotions, links with other approaches, and
      supporting research. With regard to methods of assessment of construing, major
      developments have occurred in both repertory grid and nongrid techniques, such as
      laddering. The principal advances in the applications of PCP have been in the
      clinical, educational, and organizational fields, but have by no means been
      limited to these areas. It can be concluded that PCP has met Kelly's own design
      specifications for a useful theory and that PCP can perhaps anticipate at least
      another half-century of elaboration.

PMID- 16903804
TI  - The development of coping.
AB  - Research on coping during childhood and adolescence is distinguished by its focus
      on how children deal with actual stressors in real-life contexts. Despite
      burgeoning literatures within age groups, studies on developmental differences
      and changes have proven difficult to integrate. Two recent advances promise
      progress toward a developmental framework. First, dual-process models that
      conceptualize coping as "regulation under stress" establish links to the
      development of emotional, attentional, and behavioral self-regulation and suggest
      constitutional underpinnings and social factors that shape coping development.
      Second, analyses of the functions of higher-order coping families allow
      identification of corresponding lower-order ways of coping that, despite their
      differences, are developmentally graded members of the same family. This emerging
      framework was used to integrate 44 studies reporting age differences or changes
      in coping from infancy through adolescence. Together, these advances outline a
      systems perspective in which, as regulatory subsystems are integrated, general
      mechanisms of coping accumulate developmentally, suggesting multiple directions
      for future research.

PMID- 16903805
TI  - Work group diversity.
AB  - Work group diversity, the degree to which there are differences between group
      members, may affect group process and performance positively as well as
      negatively. Much is still unclear about the effects of diversity, however. We
      review the 1997-2005 literature on work group diversity to assess the state of
      the art and to identify key issues for future research. This review points to the
      need for more complex conceptualizations of diversity, as well as to the need for
      more empirical attention to the processes that are assumed to underlie the
      effects of diversity on group process and performance and to the contingency
      factors of these processes.

PMID- 16903806
TI  - Assessment and diagnosis of personality disorder: perennial issues and an
      emerging reconceptualization.
AB  - This chapter reviews recent (2000-2005) personality disorder (PD) research,
      focusing on three major domains: assessment, comorbidity, and stability. (a)
      Substantial evidence has accrued favoring dimensional over categorical
      conceptualization of PD, and the five-factor model of personality is prominent as
      an integrating framework. Future directions include assessing dysfunction
      separately from traits and learning to utilize collateral information. (b) To
      address the pervasiveness and extent of comorbidity, researchers have begun to
      move beyond studying overlapping pairs or small sets of disorders and are
      developing broader, more integrated common-factor models that cross the Axis I
      Axis II boundary. (c) Studies of PD stability have converged on the finding that
      PD features include both more acute, dysfunctional behaviors that resolve in
      relatively short periods, and maladaptive temperamental traits that are
      relatively more stable-similar to normal-range personality traits-with increasing
      stability until after 50 years of age. A new model for assessing PD-and perhaps
      all psychopathology-emerges from integrating these interrelated
      reconceptualizations.

PMID- 16903807
TI  - An interactionist perspective on the socioeconomic context of human development.
AB  - This article addresses the relationship between socioeconomic status (SES),
      family processes, and human development. The topic is framed as part of the
      general issue of health disparities, which involves the oft-observed positive
      relationship between SES and the cognitive, social, emotional, and physical well
      being of adults and children. A review of recent research and theory identifies
      three general theoretical approaches that provide possible explanations for the
      association between SES and individual development: the social causation, social
      selection, and interactionist perspectives. Empirical evidence demonstrates
      support for the social causation view that SES affects families and the
      development of children in terms of both family stress processes (the family
      stress model) and family investments in children (the family investment model).
      However, there also is empirical support for the social selection argument that
      individual characteristics lead to differences in SES. Especially important,
      recent research is consistent with an interactionist approach, which proposes a
      dynamic relationship between SES and developmental change over time. Drawing on
      the combined set of research findings, the article concludes with the description
      of an interactionist model that serves as a heuristic for future studies of the
      links among SES, parenting behaviors, and child development.

PMID- 16903808
TI  - The neurobiology of stress and development.
AB  - Stress is a part of every life to varying degrees, but individuals differ in
      their stress vulnerability. Stress is usefully viewed from a biological
      perspective; accordingly, it involves activation of neurobiological systems that
      preserve viability through change or allostasis. Although they are necessary for
      survival, frequent neurobiological stress responses increase the risk of physical
      and mental health problems, perhaps particularly when experienced during periods
      of rapid brain development. Recently, advances in noninvasive measurement
      techniques have resulted in a burgeoning of human developmental stress research.
      Here we review the anatomy and physiology of stress responding, discuss the
      relevant animal literature, and briefly outline what is currently known about the
      psychobiology of stress in human development, the critical role of social
      regulation of stress neurobiology, and the importance of individual differences
      as a lens through which to approach questions about stress experiences during
      development and child outcomes.

PMID- 16903809
TI  - Work and vocational psychology: theory, research, and applications.
AB  - Work is integral to human functioning, and all psychologists need to understand
      the role of work in people's lives. Understanding factors influencing work
      choices and helping individuals effectively make career decisions is the focus of
      vocational psychologists. However, external changes, such as shifts in the
      economy and labor force, as well as initiatives within the field are challenging
      the assumptions within vocational psychology. This chapter reviews the empirical
      work since 1995 in four areas: (a) what factors influence career choices, (b) how
      people make career decisions, (c) how context influences career choices, and (d)
      effective interventions for help with the first three questions. The review
      focuses first on vocational psychology's rich tradition of theoretically driven
      research, and then discusses research in career development that crosses a number
      of theoretical approaches, and finally identifies the assumptions in the field
      and questions for future examination.

PMID- 16903810
TI  - Why stones break better at slow shockwave rates than at fast rates: in vitro
      study with a research electrohydraulic lithotripter.
AB  - BACKGROUND AND PURPOSE: Stones break better when the rate of shockwave (SW)
      delivery is slowed. It has been hypothesized that the greater cavitation
      accompanying a fast rate shields pulse propagation, thus interfering with the
      delivery of SW energy to the stone. We tested this idea by correlating waveforms
      measured at the SW focus with cavitation viewed using high-speed imaging.
      MATERIALS AND METHODS: A series of U30 gypsum stones held in a 2-mm mesh basket
      were exposed to 200 SWs at 30 or 120 SW/min from a research electrohydraulic
      lithotripter (HM3 clone). Waveforms were collected using a fiberoptic probe
      hydrophone. High-speed imaging was used to observe cavitation bubbles in the
      water and at the stone surface. RESULTS: Stone breakage was significantly better
      at 30 SW/min than at 120 SW/min. The rate had little effect on SW parameters in
      the water free field. In the presence of particulates released from stones, the
      positive pressure of the SW remained unaffected, but the trailing tensile phase
      of the pulse was significantly reduced at 120 SW/min. CONCLUSIONS: Cavitation
      bubbles do not persist between SWs. Thus, mature bubbles from one pulse do not
      interfere with the next pulse, even at 120 SW/min. However, cavitation nuclei
      carried by fine particles released from stones can persist between pulses. These
      nuclei have little effect on the compressive wave but seed cavitation under the
      influence of the tensile wave. Bubble growth draws energy from the negative
      pressure phase of the SW, reducing its amplitude. This likely affects the
      dynamics of cavitation bubble clusters at the stone surface, reducing the
      effectiveness of bubble action in stone comminution.

PMID- 16903811
TI  - Spondyloarthropathy: an independent risk factor for kidney stones.
AB  - PURPOSE: To better stratify risk and to verify previous prevalence reports, we
      conducted a retrospective cohort study comparing the lifetime incidence of
      nephrolithiasis in patients with spondyloarthropathies (SpA) and rheumatoid
      arthritis (RA). PATIENTS AND METHODS: Patients with SpA or rheumatoid factor
      positive RA were identified from the rheumatology clinics of two Veterans Affairs
      hospitals and the University of Minnesota. Among them, 168 were confirmed to meet
      the American College of Rheumatology criteria and gave informed consent to
      participation. They were sent a survey regarding their rheumatologic diagnosis,
      coexistent conditions, medications, and history of kidney stones. Of the total,
      143 patients responded and met the criteria for analysis. Rheumatoid arthritis
      patients were age and sex matched with SpA patients as controls. RESULTS:
      Populations were similar in all categories except that RA patients were more
      likely to have used prednisone (P < 0.001), bisphosphonates (P < 0.001), and
      calcium supplementation (P = 0.03). Kidney stones were reported by 23 (29.11%) of
      the 79 SpA patients compared with 8 (12.5%) of the 64 RA patients (chi (2) =
      5.75; P = 0.025). Subgroup analysis of self-reporting stone history in 85
      patients was found to be reliable on imaging review (sensitivity 82%; specificity
      100%). CONCLUSIONS: Self-reporting of kidney stones by patients is a reliable
      measure. Despite adjusting for medication use and matching two similar arthritic
      populations, patients with SpA had a higher incidence of kidney stones than those
      with RA. This finding suggests that SpA is an independent risk factor for
      nephrolithiasis. Future studies will evaluate urinary risk factors and
      polymorphisms in the ANKH gene that may predispose to stone formation in this
      high-risk group.

PMID- 16903812
TI  - Percutaneous nephrolithotomy for complex caliceal calculi and staghorn stones in
      children less than 5 years of age.
AB  - BACKGROUND AND PURPOSE: Treatment of children with staghorn and complex caliceal
      calculi is one of the most challenging problems in urology. We present our
      experience with percutaneous nephrolithotomy (PCNL) monotherapy for staghorn and
      complex caliceal calculi in children less than 5 years of age. PATIENTS AND
      METHODS: Between 1991 and 2004, 27 boys and 9 girls aged 11 months to 4.5 years
      underwent PCNL for staghorn (33%) or complex caliceal (67%) calculi. The average
      bulk of the stones was 140.17 +/- 42.16 mm(2) (range 61-253 mm(2)). Staging of
      the procedure was preferred in children with renal insufficiency, urinary-tract
      infection, fragmentation time >60 minutes, or a stone burden requiring more than
      two tracts. Essential steps of the technique were a dynamic contrast study to
      select the appropriate-size Amplatz sheath and ultrasound guidance for renal
      access. RESULTS: The average operative time was 72.11 +/- 28.86 minutes. The
      stone-free rate was 86%, the mean hemoglobin drop was 2.2 +/- 0.95 g/dL, and the
      mean hospital stay was 3.5 days. Less than half of the patients (42%) were
      treated in a single stage, the remainder requiring multiple procedures. Only 39%
      could be treated with a single tract. There was statistically significant
      increase in the blood loss in patients requiring multiple tracts (P = 0.008);
      however, staging the procedure did not increase the blood loss (P = 0.06).
      CONCLUSION: Percutaneous nephrolithotomy is safe and effective in children less
      than 5 years of age. Staging the procedure, instrument modification, the timed
      "multi mini-perc" technique, and ultrasound-guided access help in achieving
      maximum stone clearance with minimal morbidity.

PMID- 16903813
TI  - Advanced ureteroscopy: wireless and sheathless.
AB  - BACKGROUND: The introduction of a new generation of flexible ureteroscopes
      significantly advanced the therapeutic and diagnostic efficacy of the instrument,
      allowing greater access to all aspects of the upper urinary tract and
      facilitating wireless ureteroscopy. PATIENTS AND METHODS: Four hundred sixty
      consecutive upper urinary-tract procedures were performed utilizing the 7.5F
      actively deflectable, flexible ureteroscope. A prospective database of these
      procedures was maintained. The indications, access technique, complications,
      success rate of stone treatment, and access to lower-pole calices were evaluated.
      The accumulated clinical data were compared with a published database of 1000
      consecutive flexible ureteroscopies. RESULTS: A stent was in place or had
      recently been in place in 108 of the procedures (24%). Of the remaining 352
      flexible ureteroscopic procedures, only 11% (52) required any form of ureteral
      dilation to facilitate ureteral access. Two hundred twenty seven procedures were
      performed in which no guidewire was required to place the flexible endoscope in
      the upper urinary tract (i.e., "wireless" ureteroscopy). CONCLUSION: Wireless no
      touch flexible ureteroscopy with the new flexible instruments is a feasible and
      safe technique for diagnostic and therapeutic procedures in most patients,
      irrespective of the location of the pathology, including the distal ureter. These
      ureteroscopes, with their exaggerated deflection, are ushering in a new era of
      endoscopic treatment of the upper urinary tract. Greater instrument
      deflectability and control can lead to shorter procedures and fewer treatment
      failures.

PMID- 16903814
TI  - Retrograde intrarenal surgery as second-line therapy yields a lower success rate.
AB  - BACKGROUND AND PURPOSE: Retrograde intrarenal surgery (RIRS) is a recent addition
      to the treatment options for renal calculi. Therefore, the indications, as well
      as the predictors of success, are still being studied. Herein, we report a
      retrospective comparison of RIRS performed as the primary treatment and as second
      line therapy, mostly after shockwave lithotripsy (SWL) failure. PATIENTS AND
      METHODS: Between October 2001 and August 2004, 93 patients underwent RIRS (11% of
      all ureteroscopies), all by the same surgeon. Patients were divided into two
      groups: group 1 (n = 42) consisted of patients undergoing RIRS as a first-line
      modality and group 2 (n = 51) of those having RIRS as secondline therapy. The
      indications for RIRS in group 1 were renal calculi with prior placement of a
      double-J stent (30%), renal + ureteral stone (25%), pushback of ureteral stone
      during ureteroscopy (22%), a radiolucent stone (8%), coagulopathy, and abnormal
      renal anatomy. In group 2, the patients were initially treated by SWL (92%) or
      percutaneous nephrolithotomy. The groups did not differ significantly in
      demographic characteristics, mean stone size (9.5 and 8.7 mm, respectively), or
      stone location (in both 60% in the lower pole). The variables analyzed were
      operating time, complications, length of hospitalization, and stone-free rate.
      RESULTS: The overall stone-free rate was 73%. However, the stone-free rate was
      significantly higher in group 1 than in group 2: 80% v 67%, respectively. A
      higher complication rate and longer hospitalization were noted in group 2,
      although the difference was not statistically significant. CONCLUSIONS: When RIRS
      is performed after failed SWL, it has a lower success rate and may be associated
      with a higher morbidity rate than if it is performed as first-line therapy. These
      results suggest that the success rate of RIRS may be influenced by the same
      negative factors that reduce SWL success. Therefore, if a patient fails SWL,
      careful consideration should be given to the best second-line therapy comparing
      RIRS with percutaneous stone removal.

PMID- 16903815
TI  - Variability of protein content in calcium oxalate monohydrate stones.
AB  - BACKGROUND AND PURPOSE: Urinary stones are heterogeneous in their fragility to
      lithotripter shockwaves. As a first step in gaining a better understanding of the
      role of matrix in stone fragility, we measured extractible protein in calcium
      oxalate monohydrate (COM) stones that were extensively characterized by micro
      computed tomography (micro CT). MATERIALS AND METHODS: Stones were scanned using
      micro CT (Scanco mCT20, 34 microm). They were ground, and the protein extracted
      using four methods: 0.25M EDTA, 2% SDS reducing buffer, 9M urea buffer, and 10%
      acetic acid. Protein was measured using NanoOrange. The SDS extracts were also
      examined using polyacrylamide electrophoresis (PAGE). RESULTS: Extracted protein
      was highest with the SDS or urea methods (0.28% +/- 0.13% and 0.24% +/- 0.11%,
      respectively) and lower using the EDTA method (0.17% +/- 0.05%; P < 0.02). Acetic
      acid extracted little protein (0.006 +/- 0.002%; P < 0.001). Individual stones
      were significantly different in extractability of protein by the different
      methods, and SDS-PAGE revealed different protein patterns for individual stones.
      Extracted protein did not correlate with X-ray-lucent void percentage, which
      ranged from 0.06% to 2.8% of stone volume, or with apatite content. CONCLUSIONS:
      Extractible stone-matrix protein differs for individual COM stones, and yield is
      dependent on the extraction method. The presence of X-ray-lucent voids or minor
      amounts of apatite in stones did not correlate with protein content. The amounts
      of protein recovered were much lower than reported by Boyce, showing that these
      methods extracted only a fraction of the protein bound up in the stones. The
      results suggest that none of the methods tested will be useful for helping to
      answer the question of whether matrix content differs among stones of differing
      fragility to lithotripter shockwaves.

PMID- 16903816
TI  - Physiologic effect of nifedipine and tamsulosin on contractility of distal
      ureter.
AB  - BACKGROUND AND PURPOSE: Renal colic not only leads to significant morbidity but
      imposes a financial burden on society in lost productivity and healthcare dollars
      spent. Both tamsulosin and nifedipine can facilitate spontaneous stone passage in
      the distal ureter and reduce the associated colic. We evaluated the physiologic
      effect of these agents on the distal pig ureter. MATERIALS AND METHODS: Bilateral
      ureters were removed en bloc with the bladder trigone from three pigs. Five
      millimeter rings were taken from the intramural and distal ureter. Isometric
      tension recording was performed during both spontaneous and electrically
      stimulated contraction. Measurements of contractile interval and amplitude were
      taken in baseline buffer solution, nifedipine at 10(-6) g/L, and tamsulosin at
      10(-6) g/L. Spontaneous contractile activity was also measured with phenylephrine
      at 10(-4) g/L followed by tamsulosin at 10(-6) g/L. RESULTS: Under conditions of
      spontaneous contractility, phenylephrine decreased the contraction interval by
      46%, an effect which was reversed by tamsulosin. Tamsulosin increased the
      baseline interval by 27% (P < 0.025) and decreased the amplitude by 7% (P > 0.1).
      Nifedipine blocked all contractile activity. Under stimulated contractility,
      tamsulosin had no effect on the interval and decreased the amplitude by 7% (P >
      0.1). Nifedipine blocked all contractile activity. CONCLUSIONS: We believe that
      both tamsulosin and nifedipine prevent the disorganized antiperistalsis
      associated with ureteral spasm while allowing some degree of antegrade fluid
      bolus (stone) propagation. It is this mechanism of action that facilitates
      spontaneous passage and reduces associated renal colic when tamsulosin and
      nifedipine are used for the management of ureteral stone disease.

PMID- 16903817
TI  - Radiofrequency ablation of renal tumors: intermediate-term results.
AB  - BACKGROUND AND PURPOSE: Needle ablative therapies are being offered to patients
      presenting with small renal masses, but long-term outcomes are currently
      unavailable. We report our intermediate-term results (1-4 years) after
      radiofrequency ablation (RFA) of small (<4-cm) renal masses. PATIENTS AND
      METHODS: At our institution, all renal tumors treated using RFA since May 2001
      have been recorded in a prospective database. During this time, 94 tumors (mean
      size 2.4 cm; range 1-4.2 cm) in 78 patients were treated using a temperature
      based RFA generator by either a percutaneous (59%) or a laparoscopic approach.
      The patients followed with imaging at 6 weeks, 3 and 6 months, and every 6 months
      thereafter. Only patients with at least 12 months of follow-up were eligible for
      this analysis; the mean follow-up was 25 months. RESULTS: Of the 89% of masses
      that were biopsied, 77% were renal-cell carcinomas (RCC), of which 66% were
      Fuhrman grade 1, 31% were grade 2, and 3% were grade 3. Three recurrences were
      noted, for an overall recurrence-free rate of 96.8%. In this patient population
      with numerous comorbid conditions, there were six deaths but only one related to
      renal cancer, for a cancer-specific survival rate of 98.5% and an overall
      survival rate of 92.3%. CONCLUSION: In the intermediate term (1-4 years), the
      oncologic effectiveness of RFA appears comparable to that of traditional
      treatments offered for small renal masses. Further studies of larger numbers of
      patients with longer follow-up are needed.

PMID- 16903818
TI  - Progression of laparoscopic radical prostatectomy: improved outcomes with the
      extraperitoneal approach and a running anastomosis.
AB  - PURPOSE: To compare the operative and perioperative outcomes of patients
      undergoing either a transperitoneal or an extraperitoneal laparoscopic radical
      prostatectomy (TLRP or ELRP) with either an interrupted or a running
      urethrovesical anastomosis (IUVA or RUVA). PATIENTS AND METHODS: From January
      2003 through December 2004, 265 patients underwent LRP by one surgeon at the
      Lahey Clinic Medical Center. They were divided into three groups according to the
      operative approach (TLRP or ELRP) and the suture anastomosis (IUVA or RUVA):
      group 1 = TLRP and IUVA (N = 58; 21.6%), group 2 = TLRP and RUVA (N = 35; 13.1%),
      and group 3 = ELRP and RUVA (N = 172; 64.2%). RESULTS: Group 3 had statistically
      better outcomes, as judged by operative time (222, 191, and 170 minutes for
      groups 1, 2, and 3, respectively; P < 0.0001), postoperative analgesic use (39.6,
      30.4, and 18.9 mg of narcotic; P < 0.0001), length of stay (3.76, 2.74 days, and
      1.67 days; P < 0.0001), leak on postoperative cystogram (17.9%, 11.4%, and 3.5%;
      P = 0.001), and complication rate (32.8%, 11.4%, and 9.9%; P < 0.0001). The
      groups had similar estimated blood loss (168, 145, and 176 mL) and positive
      surgical-margin rates (15.5%, 14.3%, and 14.5%). CONCLUSIONS: We demonstrate
      improved surgical outcome for ELRP with RUVA in regard to operative time,
      analgesic use, length of stay, leak rate, and complication rate. Long-term follow
      up will determine whether a difference exists in disease recurrence, continence,
      and erectile function.

PMID- 16903819
TI  - KTP laser versus transurethral resection: early results of a randomized trial.
AB  - BACKGROUND AND PURPOSE: Many technologies have been mooted as equal to
      transurethral resection of the prostate (TURP) without gaining widespread
      acceptance because of the lack of randomized trials. The Greenlight laser system
      (Laserscope, San Jose, Ca.), an 80 W system for photovaporization of the prostate
      (PVP), was compared with TURP in such a trial. PATIENTS AND METHODS: A series of
      120 patients was randomized to undergo TURP or PVP after evaluation, which was
      repeated at 1, 3, 6, and 12 months after treatment. Irrigation use, length of
      catherization (LOC), length of hospital stay (LOS), postvoiding residual volume,
      sexual function, blood loss, cost, and operative time also were assessed.
      RESULTS: To date, 76 patients are evaluable. Both groups showed a significant (P
      < 0.5) increase in maximum flow rate from baseline. In the TURP group, flow
      increased from 8.7 to 17.9 mL/sec (149%) and in the PVP group from 8.5 to 20.6
      mL/sec (167%). The International Prostate Symptom Score decreased from 25.4 to
      12.4(50.23%) in the TURP group and from 25.7 to 12.0 (49.83%) in the PVP group.
      Postvoiding residual volumes also showed significant decreases. Similar trends
      were seen in relation to bother and quality of life scores. There was no
      difference in sexual function as measured by a questionnaire. The LOC was
      significantly less in the PVP group (P < 0.001), the mean being 12.2 hours (range
      0-24 hours) versus 44.5 hours for TURP (range 6-192 hours). A similar situation
      was seen in relation to LOS (P < 0.0001), with the mean of the PVP group being
      1.08 days (range 1-2 days) and the mean for the TURP group being 3.4 days (range
      3-9 days). Adverse events were less frequent in the PVP group, and the costs were
      22% less. CONCLUSIONS: This trial demonstrates that PVP is effective compared
      with TURP, producing equivalent improvements in flow rates and IPSS with markedly
      reduced LOS, LOC, and adverse events. Long-term follow- up is being undertaken to
      assess the durability of these results.

PMID- 16903820
TI  - Impact of cautery versus cautery-free preservation of neurovascular bundles on
      early return of potency.
AB  - PURPOSE: To update our short-term potency outcomes from a cautery-free (CFT)
      versus bipolar cautery technique to preserve the neurovascular bundles (NVB)
      during robotic laparoscopic radical prostatectomy (RLP). PATIENTS AND METHODS:
      Previously, we reported on 3-month potency outcomes in 23 men, which we now
      extend to 51 men. All men met three criteria: age <66 years, Sexual Health
      Inventory in Men (SHIM-5) score of 22 to 25, and either unilateral or bilateral
      NVB preservation at LRP. Group 1 (N = 51), the study group, had preservation of
      the NVB with CFT. Group 2 (N = 36) had traditional dissection using bipolar
      cautery. The average age and preoperative SHIM scores were similar for the two
      groups. Data were collected prospectively via validated questionnaires. Potency
      was defined as an erection adequate for vaginal penetration. All men were asked
      to estimate the fullness of erections compared with baseline (preoperative).
      RESULTS: The average age and preoperative SHIM scores were similar for both
      groups. The rate of potency at 3 months was 47% (24/51) in group 1 versus just
      8.3% (3/36) in group 2 (P < 0.001). Additionally, only 9 of 25 CFT patients (36%)
      reported zero fullness compared with 15 of 22 patients (68%) in the bipolar
      cauterytreated group (P = 0.03). CONCLUSIONS: With expanded experience, there was
      no change in 3-month return of sexual function (47%) compared with our initial
      publication. This result further supports the importance of avoiding cautery when
      controlling the vascular pedicle and dissecting the NVB.

PMID- 16903821
TI  - Serial microscopic changes in cell proliferation and apoptosis in obstructed
      ureter of rat.
AB  - PURPOSE: We investigated the histologic findings and serial changes in cell
      proliferation and apoptosis in obstructed rat ureters. MATERIALS AND METHODS:
      After unilateral ligation of the ureter, animals from each of five groups of
      Sprague- Dawley rats were sacrificed for examination at 1, 5, 10, 15, 20, 25, 30,
      or 35 days. Cell division was detected with proliferating cell nuclear antigen
      (PCNA) immunohistochemistry, and apoptosis was detected with terminal
      deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) in
      situ nick-end labeling (TUNEL) study. RESULTS: The epithelial layer was thickened
      in 5-day-obstructed ureters (5 DOUs). The severity of thickening of the fibrous
      and smooth-muscle layers progressed consistently to 15 DOUs and were maintained
      in 35 DOUs. Expression of PCNA in the epithelial layer was present in every
      ureter, and a significant increase in the number of labeled cells was present in
      1 and 5 DOUs. Expression of PCNA in the fibrous and smoothmuscle layers was
      detectable in 10 DOUs and was maintained in 20 DOUs, after which, it declined
      significantly in the 25 DOUs. TUNEL-positive cells in the epithelial layer were
      shown in 10, 15, 20, 25, 30, and 35 DOUs, with the peak being reached at 25 days.
      TUNEL-positive cells in the fibrous and smooth-muscle layers were found in 25,
      30, and 35 DOUs. CONCLUSIONS: Cell proliferation and apoptosis may play an
      important role in the pathogenesis of damage in obstructed ureters. Peak times of
      proliferation and apoptosis were different in the epithelial and fibrous and
      smooth-muscle layers.

PMID- 16903823
TI  - Protein kinase Czeta and glucose uptake.
AB  - Protein kinase Czeta (PKCzeta) is a member of the PKC family, serving downstream
      of insulin receptor and phosphatidylinositol (PI) 3-kinase. Many evidences
      suggest that PKCzeta plays a very important role in activating glucose transport
      response. Not only insulin but also glucose and exercise can activate PKCzeta
      through diverse pathways. PKCzeta activation and activity are impaired with
      insulin resistance in muscle and adipose tissues of type II diabetes individuals,
      but heightened in liver tissue, wherein it also increases lipid synthesis
      mediated by SREBP-1c (sterol-regulatory element-binding protein). Many studies
      have focused on linkage between PKCzeta and GLUT4 translocation and activation.
      Exploring the molecular mechanisms and pathways by which PKCzeta mediates glucose
      transport will highlight the insulin-signaling pathway.

PMID- 16903824
TI  - Role of ApoE in conformation-prone diseases and atherosclerosis.
AB  - Three isoforms of human plasma apolipoprotein E (apoE) are ligands to lipoprotein
      receptors and influence in different manner the synthesis and catabolism of pro
      atherogenic triglyceride-rich lipoproteins. Among three isoforms, the apoE4
      isoform is associated with increased frequency of atherosclerosis and Alzheimer's
      disease (AD). The conformational transitions of beta-amyloid (Abeta) influenced
      by apoE and serum amyloid P (SAP) component are key events in AD development, the
      accumulation of intermediate diffusible and soluble oligomers of Abeta being of
      particular significance. SAP and apoE, in a different manner for the three
      isoforms, serve as "pathological" chaperones during the aggregation of Abeta
      considered as a conformation-prone process. In turn, apoE consisting of two
      domains self-associates in solution and intermediate structures differently
      populated for the three isoforms exist. The different structures of the three
      isoforms determine their different distribution among various plasma
      lipoproteins. The structural and metabolic consideration of the common apoE
      pathway(s) in two pathologies assumes four molecular targets for AD correction:
      (i) inhibition of the accumulation of diffusible soluble Abeta oligomers; (ii)
      inhibition of apoE synthesis and secretion by astrocytes, in particular, under
      lipid-lowering therapy; (iii) inhibition of the binding of apoE and/or SAP to
      Abeta; (iv) stimulation of the expression of cholesterol transporter ABCA1.

PMID- 16903825
TI  - Sphingolipids and cell signaling: involvement in apoptosis and atherogenesis.
AB  - This review considers various functional aspects of cell sphingolipids
      (sphingomyelin, ceramides) and lysosphingolipids (sphingosine-1-phosphate (S1P)
      and sphingosine phosphorylcholine). Good evidence now exists that they are
      actively involved in numerous cell-signaling processes. The enzymes responsible
      for formation and interconversion of cell sphingolipids (sphingomyelinases,
      ceramidase, sphingosine kinase, S1P-lyase) exhibit high sensitivity to various
      stimulating factors. This determines the content of individual cell sphingolipids
      and therefore the mode of cell response. Special attention is paid to
      preferential localization of sphingolipids in the rigid plasma membrane domains
      (rafts) coupled to many signal proteins. The suggestion is discussed that
      ceramide signaling may be based on the modification of fine molecular
      interactions in lipid rafts, resulting in its clusterization inducing the signal
      transduction. The review also highlights involvement of sphingolipids in cell
      proliferation, apoptosis, and in processes implicated to atherosclerosis.

PMID- 16903826
TI  - Does a deficiency of the signal recognition particle (SRP)-pathway affect the
      biosynthesis of its components in Saccharomyces cerevisiae and Escherichia coli?
AB  - We studied the behavior of the signal recognition particle (SRP) components in
      Saccharomyces cerevisiae upon deficiencies of the protein transport caused by the
      absence of the SRP membrane receptor alpha-subunit. A decrease in the
      concentration of the SRP membrane receptor alpha-subunit in the cell
      significantly decreased the level of an SRP component, protein SRP72, as well as
      the levels of mRNAs of SRP protein components and the SRP receptor beta-subunit.
      But the amount of 7SL RNA remained unchanged. In contrast, in Escherichia coli
      cells the gradual decrease in the level of the protein FtsY (a homolog of the SRP
      membrane receptor alpha-subunit) was not associated with changes in the Ffh
      protein level.

PMID- 16903827
TI  - On the nature of obligate intracellular symbiosis of rickettsiae--Rickettsia
      prowazekii cells import mitochondrial porin.
AB  - Mitochondrial porin was identified in Rickettsia prowazekii by Western blot
      analysis of whole cells and membrane fractions with monoclonal antibody against
      porin VDAC 1 of animal mitochondria. Using the BLAST server, no protein sequences
      homologous to mitochondrial porin were found among the rickettsial genomes.
      Rickettsiae also do not contain their own porin. The protein imported by
      rickettsiae is weakly extracted by nonionic detergents and, like porin in
      mitochondria, is insensitive to proteinase K in whole cells. Immunocytochemical
      analysis showed that it localizes to the outer membrane of the bacterial cells.
      These data support an earlier suggestion about import by rickettsiae of
      indispensable proteins from cytoplasm of the host cell as a molecular basis of
      obligate intracellular parasitism. They are also consistent with the hypothesis
      invoking a transfer of genes specifying surface proteins from the last common
      ancestor of rickettsiae and mitochondria to the host genome, and preservation by
      rickettsiae of the primitive ability to import these proteins.

PMID- 16903828
TI  - Influence of poly(ADP-ribose) polymerase-1 and its apoptotic 24-kD fragment on
      repair of DNA duplexes in bovine testis nuclear extract.
AB  - Effects of exogenous proteins poly(ADP-ribose) polymerase-1 (PARP1) and its 24-kD
      proteolytic fragment (p24) on the repair of DNA duplexes containing a one
      nucleotide gap with furan phosphate or phosphate group at the 5'-end of the
      downstream primer were studied in bovine testis nuclear extract. These damaged
      DNAs are repaired by the long-patch or short-patch subpathways of base excision
      repair (BER), respectively. Exogenous PARP1 and p24 decreased the efficiency of
      gap filling DNA synthesis for both duplexes, but did not influence the ligation
      stage in the repair of DNA duplex by the short-patch subpathway. Under the same
      conditions, these proteins inhibited strand-displacement DNA synthesis and
      decreased the efficiency of the flap endonuclease 1 (FEN1)-catalyzed endonuclease
      reaction in the nuclear extract, blocking repair of DNA duplex by the long-patch
      subpathway. Addition of exogenous PARP1 and p24 also reduced the efficiency of UV
      light crosslinking of extract BER proteins to the photoreactive BER intermediates
      carrying a nick. Thus, PARP1 and p24 interact with DNA intermediates of BER and
      compete with nuclear extract proteins for binding to DNA. The interaction of
      PARP1 and p24 with DNA intermediates of the long-patch subpathway of BER resulted
      in inhibition of subsequent stages of the repair mediated by this mechanism.
      However, on recovery of the intact structure of DNA duplex by the short-patch
      subpathway, PARP1 and p24 suppressed the repair of the one nucleotide gap less
      efficiently and failed to influence the final stage of the repair, ligation.

PMID- 16903829
TI  - Analysis of specificity of antibodies against synthetic fragments of different
      neuronal nicotinic acetylcholine receptor subunits.
AB  - We have compared specificity of a panel of polyclonal antibodies against
      synthetic fragments of the alpha7 subunit of homooligomeric acetylcholine
      receptor (AChR) and some subunits of heteromeric AChRs. The antibody interaction
      with extracellular domain of alpha7 subunit of rat AChR (residues 7-208) produced
      by heterologous expression in E. coli and rat adrenal membranes was investigated
      by the ELISA method. For comparison, membranes from the Torpedo californica ray
      electric organ enriched in muscle-type AChR and polyclonal antibodies raised
      against the extracellular domain (residues 1-209) of the T. californica AChR
      alpha1 subunit were also used. Antibody specificity was also characterized by
      Western blot analysis using rat AChR extracellular domain alpha7 (7-208) and the
      membrane-bound T. californica AChR. Epitope localization was analyzed within the
      framework of AChR extracellular domain model based on the crystal structure of
      acetylcholine-binding protein available in the literature. According to this
      analysis, the 179-190 epitope is located on loop C, which is exposed and mobile.
      Use of antibodies against alpha7 (179-190) revealed the presence of alpha7 AChR
      in rat adrenal membranes.

PMID- 16903830
TI  - Influence of lipopolysaccharides and lipids A from some marine bacteria on
      spontaneous and Escherichia coli LPS-induced TNF-alpha release from peripheral
      human blood cells.
AB  - Some endotoxic properties of lipopolysaccharides (LPS) and lipids A (LA) from the
      marine bacteria Marinomonas communis ATCC 27118(T), Marinomonas mediterranea ATCC
      700492(T), and Chryseobacterium indoltheticum CIP 103168(T) were studied. The
      preparations tested were shown to have high 50% lethal doses (4 microg per mouse
      for LPS from M. mediterranea and more than 12 microg per mouse for two other LPS
      and LA from C. indoltheticum) and were moderate (371 +/- 37 pg/ml at 10 microg/ml
      of C. indoltheticum LPS), weak (148 +/- 5 pg/ml at 1 microg/ml of M. mediterranea
      LPS), and zero (LA and LPS from M. communis and LA from C. indoltheticum)
      inducers of tumor necrosis factor alpha (TNF-alpha) release from peripheral human
      blood cells. The capacity of the LA and LPS samples from marine bacteria to
      inhibit TNF-alpha release induced by LPS from Escherichia coli O55 : B5 (10
      ng/ml) was also studied.

PMID- 16903831
TI  - Mouse retinal progenitor cell (RPC) cocultivation with retinal pigment epithelial
      cell culture affects features of RPC differentiation.
AB  - We provide evidence that coculturing of retinal progenitor cells (RPC) with
      retinal pigment epithelial cells significantly biases the standard in vitro RPC
      differentiation patterns. In particular, in cocultivation experiments RPCs lost
      the ability to differentiate spontaneously and displayed approximately 2.1-2.4
      fold increase in immunoreactivity to the neural stem cell marker nestin and
      approximately 1.6-1.7-fold increase in rod photoreceptor cell rhodopsin marker
      immunoreactivity. The data suggest the influence of the intercellular interaction
      networks on RPC differentiation.

PMID- 16903832
TI  - Carbohydrate-containing polymers of the cell wall of the thermophilic
      streptomycete Streptomyces thermoviolaceus subsp. thermoviolaceus VKM Ac-1857T.
AB  - Anionic polymers of the cell surface of a thermophilic streptomycete were
      investigated. The cell wall of Streptomyces thermoviolaceus subsp.
      thermoviolaceus VKM Ac-1857(T) was found to contain polymers with different
      structure: teichoic acid--1,3-poly(glycerol phosphate), disaccharide-1-phosphate
      polymer with repeating unit -6)-alpha-Galp-(1-->6)-alpha-GlcpNAc-P-, and
      polysaccharide without phosphate with repeating unit -->6)-alpha-GalpNAc-(1-->3)
      beta-GalpNAc-(1-->. Disaccharide-1-phosphate and polysaccharide without phosphate
      have not been described earlier in prokaryotic cell walls.

PMID- 16903833
TI  - Ion-exchange properties of cell walls of Spinacia oleracea L. roots under
      different environmental salt conditions.
AB  - Ion-exchange properties of the polymeric matrix of cell walls isolated from roots
      of 55-day-old Spinacia oleracea L. (Matador cv.) plants grown in nutrient
      solution in the presence of 0.5, 150, and 250 mM NaCl and from roots of Suaeda
      altissima L. Pall plants of the same age grown in the presence of 0.5 and 250 mM
      NaCl were studied. The ion-exchange capacity of the spinach cell walls was
      determined at pH values from 2 to 12 and different ionic strength of the solution
      (10 and 250 mM NaCl). In the structure of the root cell walls, four types of
      ionogenic groups were found: amine, two types of carboxyl (the first being
      galacturonic acid residue), and phenolic groups. The content of each type of
      group and their ionization constants were evaluated. The ion-exchange properties
      of spinach and the halophyte Suaeda altissima L. Pall were compared, and the
      qualitative composition of the ion-exchange groups in the cell walls of roots of
      these plants appeared to be the same and not depend on conditions of the root
      nutrition. The content of carboxyl groups of polygalacturonic acid changed in the
      cell walls of the glycophyte and halophyte depending on the salt concentration in
      the medium. These changes in the composition of functional groups of the cell
      wall polymers seemed to be a response of these plants to salt and were more
      pronounced in the halophyte. A sharp increase in the NaCl concentration in the
      medium caused a decrease in pH in the extracellular water space as a result of
      exchange reactions between sodium ions entering from the external solution and
      protons of carboxyl groups of the cell walls. The findings are discussed from the
      standpoint of involvement of root cell walls of different plant species in
      response to salinity.

PMID- 16903835
TI  - Study of active site topography of rat liver mitochondrial dicarboxylate
      transporter using lipophilic substrate derivatives.
AB  - Earlier it has been demonstrated that the active site (substrate-binding site +
      active site channel) of rat liver mitochondrial dicarboxylate transporter is
      characterized by rather complex topography. Probing the active site with 2
      monoalkylmalonates revealed the existence of internal and external lipophilic
      areas separated by a polar region. A two substrate-binding site model of the
      transporter has been supposed. The correctness of this model has been evaluated
      by probing the active site with O-acyl-L-malates differing from 2
      monoalkylmalonates by 0.23 nm longer distance from the anion groups to the
      aliphatic chain. Changes in the polar group of the probe did not prevent its
      binding and showed the same variable lipophilicity pattern for the transporter
      channel. Probing with alpha,omega-alkylene dimalonates did not reveal the second
      substrate-binding site at the active site. The substrate-binding site did not
      show any differences in affinity to O-acyl-derivatives of L-malate and D-malate,
      except L-malate binds more effectively than D-malate. This suggests involvement
      of the L-malate hydroxyl group in substrate binding and stereospecific behavior
      of the transporter substrate-binding site. A modified one substrate-binding site
      model of the dicarboxylate transporter is discussed.

PMID- 16903834
TI  - Expression of outer mitochondrial membrane cytochrome b5 in Escherichia coli.
      purification of the recombinant protein and studies of its interaction with
      electron-transfer partners.
AB  - In the present work, we report expression in Escherichia coli, purification, and
      characterization of recombinant full-length cytochrome b(5) from outer
      mitochondrial membrane. Optimization of expression conditions for cytochrome b(5)
      from outer mitochondrial membrane allowed reaching expression level up to 10(4)
      nmol of the hemeprotein per liter of culture. Recombinant cytochrome b(5) from
      outer mitochondrial membrane was purified from cell lysate by using metal
      affinity chromatography. It has physicochemical, spectral, and immunochemical
      properties similar to those of cytochrome b(5) from rat liver outer mitochondrial
      membrane. Immobilized recombinant mitochondrial cytochrome b(5) was used as
      affinity ligand to study its interaction with electron transfer proteins. By
      using this approach, it is shown that in interaction of NADPH:cytochrome P450
      reductase with both forms of cytochrome b(5) an important role is played by
      hydrophobic interactions between proteins, although the contribution of these
      interactions in complex formation with NADPH:cytochrome P450 reductase is
      different for isoforms of cytochrome b(5).

PMID- 16903836
TI  - Coexpression of all constituents of the cholesterol hydroxylase/lyase system in
      Escherichia coli cells.
AB  - Using the pTrc99A/P450scc vector, a plasmid was constructed in which cDNAs for
      cytochrome P450scc, adrenodoxin reductase, and adrenodoxin are situated in a
      single expression cassette. This plasmid was shown to direct the synthesis of all
      the above proteins in Escherichia coli. Their localization in the E. coli cells
      and stoichiometry were determined. Cell homogenates exhibited cholesterol
      hydroxylase/lyase activity, due to catalytically active forms of all three
      proteins. Thus, the full set of constituents of the mammalian cholesterol
      hydroxylase/lyase system was shown to be synthesized in bacterial cells for the
      first time.

PMID- 16903837
TI  - Nickase and a protein encoded by an open reading frame downstream from the
      nickase BspD6I gene form a restriction endonuclease complex.
AB  - We are the first to have isolated a protein (186 amino acid residues) encoded by
      the open reading frame adjacent to the end of the BspD6I nickase (N.BspD6I) gene.
      Cleavage of both DNA strands near the sequence recognized by nickase (5 -GAGTC/5 
      GACTC) occurs when this protein is added to the reaction mixture containing
      N.BspD6I. The protein encoded by the open reading frame and the nickase are
      suggested to be subunits of heterodimeric restriction endonuclease R.BspD6I.

PMID- 16903838
TI  - A new scaleable freeze-thaw technology for bulk protein solutions.
AB  - A new method of freeze-thaw is described using experimental data obtained from
      freezing of purified rhGH (recombinant human growth hormone). The method is based
      on freezing protein solutions in rectangular rather than cylindrical containers.
      It is hypothesized that the change in container geometry allows for linear scale
      up of the freeze-thaw operation based on equivalency of temperature-time profile.
      The hypothesis is tested using freeze-thaw data from a miniature (30 ml) and a
      2.4 litre container. Computational fluid dynamics techniques are used to simulate
      the freeze process and the simulations are compared with experimental results.
      Protein quality is assessed as a function of freeze conditions using dynamic
      light scattering, circular CD, size-exclusion and reverse-phase HPLC
      measurements. The results demonstrate the applicability of the new approach.
      Freezing of rhGH solution at concentrations of approx. 30 mg/ml is shown to be
      possible with no damage to the molecule for up to five cycles of freeze-thaw. A
      nitrogen blast chest-freezer is designed and evaluated as part of the process.
      The refrigeration system and the freeze-thaw method can be used to freeze-thaw
      bulk protein solutions for development work and has the potential for transfer to
      manufacturing.

PMID- 16903839
TI  - Obesity in pregnancy.
AB  - Overweight and obesity are common findings in women of reproductive age in the
      UK; as 32% of 35- to 64-year-old women are overweight and 21% obese. Obesity
      causes major changes in many features of maternal intermediary metabolism.
      Insulin resistance appears to be central to these changes and may also be
      involved in increased energy accumulation by the fetus. Maternal obesity is
      associated with many risks to the pregnancy, with increased risk of miscarriage
      (three-fold) and operative delivery (20.7 versus 33.8% in the obese and 47.4% in
      the morbidly obese group). Other risks to the mother include an increased risk of
      pre-eclampsia (3.9 versus 13.5% in the obese group) and thromboembolism (0.05
      versus 0.12% in the obese group). There are risks to the fetus with increased
      perinatal mortality (1.4 per 1000 versus 5.7 per 1000 in the obese group) and
      macrosomia (>90th centile; 9 versus 17.5% in the obese group). Maternal obesity
      is associated with an increased risk of obesity in the long term. Obese woman
      should try to lose weight before pregnancy but probably not during pregnancy.
      There is no real evidence base for the management of maternal obesity but some
      practical suggestions are made.

PMID- 16903841
TI  - Operative laparoscopy for unruptured ectopic pregnancy in a caesarean scar.
AB  - Eight women diagnosed by transvaginal ultrasonography with unruptured caesarean
      scar pregnancy underwent operative laparoscopy as an alternative treatment to
      laparotomy. The ultrasonographic diagnosis of caesarean scar pregnancy was
      confirmed in all women at laparoscopy. None of the women required conversion of
      the procedure to laparotomy. The total operative time ranged from 75 to 120
      minutes. The total blood loss was limited, ranging from 50 to 200 ml. All women
      tolerated the operation well and had uneventful recoveries. Our results show that
      in the hands of a well-trained operator, laparoscopy appears to be a reasonable
      alternative for the management of an unruptured caesarean scar pregnancy.

PMID- 16903840
TI  - The influence of body weight on response to ovulation induction with
      gonadotrophins in 335 women with World Health Organization group II anovulatory
      infertility.
AB  - OBJECTIVE: To assess the influence of body weight on the outcome of ovulation
      induction in women with World Health Organization (WHO) group II anovulatory
      infertility. DESIGN: The combined results of two studies in which either a highly
      purified urinary follicle-stimulating hormone or highly purified urinary
      menotrophin were compared with recombinant follicle-stimulating hormone. SETTING:
      Thirty-six fertility clinics. POPULATION: A total of 335 women with WHO group II
      anovulatory infertility failing to ovulate or conceive on clomifene citrate.
      METHODS: Ovarian stimulation using a low-dose step-up protocol. MAIN OUTCOME
      MEASURES: The effects of body weight on ovarian response, ovulation rate and
      pregnancy rate after one treatment cycle. RESULTS: With increasing body mass
      index (BMI), a higher threshold dose of gonadotrophins was required and there
      were more days of stimulation; yet, despite a greater concentration of antral
      follicles, there were fewer intermediate and large follicles. There was no
      difference in the rates of ovulation and clinical pregnancy in relation to body
      weight. CONCLUSIONS: Body weight affects gonadotrophin requirements but not
      overall outcome of ovulation induction in women with anovulatory polycystic ovary
      syndrome and a BMI of less than 35 kg/m2.

PMID- 16903842
TI  - Active warming as emergency interventional care for the treatment of pelvic pain.
AB  - OBJECTIVE: To assess whether local active warming can lessen acute pelvic pain of
      gynaecological origin compared with traditional methods in a prehospital setting.
      DESIGN: Prospective, randomised, single-blinded study. Setting. Prehospital
      emergency system. Population. Women calling emergency ambulance for pelvic pain.
      METHODS: Women were randomised in two groups: resistive heating (group 1) or
      passive warming (group 2), each treatment was initiated at the emergency site.
      MAIN OUTCOME MEASURES: Pain on visual analogue scale (VAS), anxiety and nausea,
      given as mean (SD). RESULTS: Prior to the interventions, all women were
      vasoconstricted and had comparable pain scores. Then, group 1 showed a
      significant (P < 0.01) reduction in pain (VAS: 72.2 [10.5] mm to 32.4 [18.0] mm),
      anxiety (VAS: 59.0 [10.9] mm to 37.5 [24.1] mm), nausea (VAS: 42.7 [6.2] mm to
      21.6 [5.0] mm) and heart rate (101 [12] beats per minute [bpm] to 59 [8] bpm), as
      well as in the number of vasoconstricted women (from 19/19 (constricted/dilated)
      to 2/19 (constricted/dilated)), whereas scores in group 2 remained unchanged.
      There were no significant changes in blood pressure in either group. CONCLUSIONS:
      Local warming is an effective emergency care measure for acute pelvic pain.

PMID- 16903843
TI  - Can we improve the diagnosis of rupture of membranes? The value of insulin-like
      growth factor binding protein-1.
AB  - Our objective was to assess the value of insulin-like growth factor binding
      protein-1 (IGFBP-1) and other tests for the diagnosis of rupture of the membranes
      (ROM). We included 49 women with suspected ROM. The gold standard for membranes
      status was defined based on clinical examination, ultrasonography, tests results
      (except IGFBP-1) and labour information. Sensitivity, specificity, positive
      predictive value and negative predictive value of each test were as follows,
      respectively: IGFBP-1 (86, 74, 73 and 87%); bromothymol (64, 100, 100 and 77%);
      fern test (62, 96, 93 and 75%) and ultrasonography (19, 100, 100 and 61%). The
      detection of IGFBP-1 in vaginal secretions has high sensitivity for the diagnosis
      of ROM.

PMID- 16903844
TI  - Prognosis for the co-twin following single-twin death: a systematic review.
AB  - BACKGROUND: Following single-twin death, the perinatal mortality and morbidity
      for the surviving co-twin is increased but difficult to quantify. We present data
      on prognosis from a systematic review. OBJECTIVES: We aimed to determine the
      incidence of a) co-twin death, b) neurological abnormality and c) preterm
      delivery for the surviving co-twin following single-twin death after 14 weeks of
      gestation. SEARCH STRATEGY: Literature was identified by searching two
      bibliographical databases and specialist journals between 1990 and 2005.
      SELECTION CRITERIA: The selected studies of > or = 5 cases reported on perinatal
      death and/or neurodevelopmental delay of the surviving co-twin. DATA COLLECTION
      AND ANALYSIS: Studies were assessed for quality and data extracted to allow
      computation of rates. The data were inspected for heterogeneity using a Forrest
      plot and examined statistically using the chi-square test. Data from individual
      studies were pooled within subgroups defined by prognosis. MAIN RESULTS: The
      search strategy yielded 632 potentially relevant citations. Full manuscripts were
      retrieved for 54 citations and 28 studies were finally included in the review.
      Following the death of one twin, the risk of monochorionic and dichorionic co
      twin demise was 12% (95% CI 7-11) and 4% (95% CI 2-7), respectively. The risk of
      neurological abnormality in the surviving monochorionic and dichorionic co-twin
      was 18% (95% CI 11-26) and 1% (95% CI 0-7), respectively. The risk of preterm
      delivery was 68% (95% CI 56-78) and 57% (95% CI 34-77), respectively. Where there
      was comparative data within studies, the odds of monochorionic co-twin
      intrauterine death was six times that of dichorionic twins (OR 6.04 [95% CI 1.84
      19.87]). Neurological abnormality was also higher in monochorionic compared with
      dichorionic pregnancies (OR 4.07 [95% CI 1.32-12.51]). AUTHOR'S CONCLUSIONS: More
      prospective research is required to inform decision making on this subject,
      especially with data that allow stratification based upon chorionicity.

PMID- 16903845
TI  - Is obesity an inflammatory illness? Role of low-grade inflammation and macrophage
      infiltration in human white adipose tissue.
AB  - There are at least two scientific evidences of human obesity as a chronic
      inflammatory illness: first, the well-described moderate increase of inflammatory
      factors in the circulation in obese subjects, and second, the recent
      identification of macrophage cells infiltrating the white adipose tissue (WAT).
      These observations led to a revision of the physiopathology of obesity and its co
      morbidities. It has been suggested that the 'low-grade' inflammatory state
      associates with metabolic and cardiovascular complications of obesity. Weight
      loss is able to improve this inflammatory state by both significantly decreasing
      circulating inflammatory molecules and macrophage cell infiltration in WAT
      depots. However, the mechanisms of WAT macrophage recruitment into the adipose
      tissue and their role in obesity complications have not been defined. This review
      aims to point out the knowledge on inflammatory cytokines associated with obesity
      and focuses on macrophage infiltration in human WAT, discussing their recruitment
      and role. The interactions of macrophages with adipocytes will certainly be the
      subject of intense investigations in the future.

PMID- 16903846
TI  - The secreted autotransporter toxin, Sat, functions as a virulence factor in
      Afa/Dr diffusely adhering Escherichia coli by promoting lesions in tight junction
      of polarized epithelial cells.
AB  - Afa/Dr diffusely adhering Escherichia coli (DAEC) strains are responsible for
      urinary tract and intestinal infections. Both in intestine and kidney, the
      epithelial cells forming epithelium are sealed by junctional domains. We provide
      evidence that the Secreted autotransporter toxin, Sat, belonging to the subfamily
      of serine protease autotransporters of Enterobacteriaceae (SPATEs), acts as a
      virulence factor in Afa/Dr DAEC by promoting lesions in the tight junctions (TJs)
      of polarized epithelial Caco-2/TC7 cells. Southern blot analysis reveals that the
      prototype strains of the subclass-1 and subclass-2 typical Afa/Dr DAEC strains,
      hybridize with a sat probe. Using the wild-type IH11128 strain, the recombinant
      E. coli AAEC185 strain that expresses Sat, the recombinant E. coli that expresses
      both Dr adhesin and Sat, we report that Sat in monolayers of cultured enterocyte
      like Caco-2/TC7 cells, induces rearrangements of the TJs-associated proteins ZO
      1, ZO-3 and occludin, and increases the formation of domes as the result of an
      increase in the paracellular permeability without affecting the transepithelial
      electrical resistance of the cell monolayers. Moreover, we observe that Sat
      induced disassembly of TJs-associated proteins is dependent on the serine
      protease motif. Finally, an analysis of the prevalence of the sat gene in three
      collections of Afa/Dr DAEC strains collected from the stools of children with and
      without diarrhoea, and from the urine of patients with urinary tract infection
      (UTI) shows that: (i) the sat gene is highly prevalent in UTI-associated Afa/Dr
      DAEC strains (88% positive), (ii) the sat gene is generally absent from Afa/Dr
      DAEC strains collected from the stools of children without diarrhoea (16%
      positive); whereas (iii) it is present in about half of the strains collected
      from the stools of children with diarrhoea (46% positive).

PMID- 16903847
TI  - Erythropoietin and GDNF enhance ventral mesencephalic fiber outgrowth and
      capillary proliferation following neural transplantation in a rodent model of
      Parkinson's disease.
AB  - Low dopaminergic cell survival and suboptimal fiber reinnervation are likely
      major contributing factors for the limited benefits of neural transplantation in
      Parkinson's disease (PD) patients. Glial cell lined-derived neurotrophic factor
      (GDNF) has been shown to enhance dopaminergic cell survival and fiber outgrowth
      of the graft site as well as promote behavioral recovery in rodent models of PD,
      while erythropoietin (EPO) can produce dopaminergic neuroprotective effects
      against 6-hydroxydopamine (6-OHDA) exposure on cultured neurons and 1-methyl-4
      phenyl-1,2,3,6-tetrahydropyridine-treated mice. The aim of this study was to
      determine if fetal ventral mesencephalic (FVM) tissue exposed to hibernation
      media containing a combination of GDNF and EPO could enhance dopaminergic graft
      survival, striatal reinnervation and functional recovery in a 6-OHDA rodent model
      of PD. FVM tissue was dissected from 14-day-old rat fetuses and placed for 6 days
      in hibernation media alone, and in hibernation media that received either a daily
      administration of GDNF, EPO or a combination of GDNF and EPO. Following
      hibernation, FVM cells were transplanted as a single cell suspension into the
      striatum of unilateral 6-OHDA-lesioned rats. Rotational behavioral assessment
      revealed animals that received FVM tissue exposed to GDNF, EPO or the combination
      of both drugs had accelerated functional recovery. Immunohistochemical and
      stereological assessment revealed a significant increase in graft fiber density
      and angiogenesis into the graft when compared with control. These findings
      suggest that the hibernation of FVM tissue in a combination of GDNF and EPO can
      enhance graft efficacy and may have important implications for tissue preparation
      protocols for clinical neural transplantation in PD.

PMID- 16903848
TI  - Astroglia up-regulate transcription and secretion of 'readthrough'
      acetylcholinesterase following oxidative stress.
AB  - Novel and diverse functions of glial cells are currently the focus of much
      attention [A. Volterra and J. Meldolesi (2005) Nature Rev. 6, 626-640]. Here we
      present evidence that rat astroglia release acetylcholinesterase (AChE) as part
      of their response to hypoxic damage. Exposure of astroglia to tert-butyl
      hydroperoxide, and hence oxidative stress, subsequently leads to a switching in
      mRNA from the classical membrane-bound T-AChE to a preferential increase in the
      splice variant for a soluble form, R-AChE, This change in expression is reflected
      in increased perinuclear and reduced cytoplasmic AChE staining of the insulted
      glial cells, with a concomitant and marked increase in extracellular secretion
      that peaks at 1 h post-treatment. An analogous increase in R-AChE, over a similar
      time scale, occurs in response to psychological stress [D. Kaufer et al. (1998)
      Nature 93, 373-377], as well as to head injury and stroke [E. Shohami et al.
      (1999) J. Neurotrauma 6, 365-76]. The data presented here suggest that glial
      cells may be key chemical intermediaries in such situations and, perhaps more
      generally in pathological conditions involving oxidative stress, such as
      neurodegeneration.

PMID- 16903849
TI  - Cell culture models to investigate the selective vulnerability of motoneuronal
      mitochondria to familial ALS-linked G93ASOD1.
AB  - Mitochondrial damage induced by superoxide dismutase (SOD1) mutants has been
      proposed to have a causative role in the selective degeneration of motoneurons in
      amyotrophic lateral sclerosis (ALS). In order to investigate the basis of the
      tissue specificity of mutant SOD1 we compared the effect of the continuous
      expression of wild-type or mutant (G93A) human SOD1 on mitochondrial morphology
      in the NSC-34 motoneuronal-like, the N18TG2 neuroblastoma and the non-neuronal
      Madin-Darby Canine Kidney (MDCK) cell lines. Morphological alterations of
      mitochondria were observed in NSC-34 expressing the G93A mutant (NSC-G93A) but
      not the wild-type SOD1, whereas a ten-fold greater level of total expression of
      the mutant had no effect on mitochondria of non-motoneuronal cell lines.
      Fragmented network, swelling and cristae remodelling but not vacuolization of
      mitochondria or other intracellular organelles were observed only in NSC-G93A
      cells. The mitochondrial alterations were not explained by a preferential
      localization of the mutant within NSC-G93A mitochondria, as a higher amount of
      the mutant SOD1 was found in mitochondria of MDCK-G93A cells. Our results suggest
      that mitochondrial vulnerability of motoneurons to G93ASOD1 is recapitulated in
      NSC-34 cells, and that peculiar features in network dynamics may account for the
      selective alterations of motoneuronal mitochondria.

PMID- 16903850
TI  - Inhibition of constitutive inward rectifier currents in cerebellar granule cells
      by pharmacological and synaptic activation of GABA receptors.
AB  - gamma-Aminobutyric acid (GABA)(B) receptors are known to enhance activation of
      Kir3 channels generating G-protein-dependent inward rectifier K(+)-currents
      (GIRK). In some neurons, GABA(B) receptors either cause a tonic GIRK activation
      or generate a late K(+)-dependent inhibitory postsynaptic current component.
      However, other neurons express Kir2 channels, which generate a constitutive
      inward rectifier K(+)-current (CIRK) without requiring G-protein activation. The
      functional coupling of CIRK with GABA(B) receptors remained unexplored so far.
      About 50% of rat cerebellar granule cells in the internal granular layer of P19
      26 rats showed a sizeable CIRK current. Here, we have investigated CIRK current
      regulation by GABA(B) receptors in cerebellar granule cells, which undergo
      GABAergic inhibition through Golgi cells. By using patch-clamp recording
      techniques and single-cell reverse transcriptase-polymerase chain reaction in
      acute cerebellar slices, we show that granule cells co-express Kir2 channels and
      GABA(B) receptors. CIRK current biophysical properties were compatible with Kir2
      but not Kir3 channels, and could be inhibited by the GABA(B) receptor agonist
      baclofen. The action of baclofen was prevented by the GABA(B) receptor blocker
      CGP35348, involved a pertussis toxin-insensitive G-protein-mediated pathway, and
      required protein phosphatases inhibited by okadaic acid. GABA(B) receptor
      dependent CIRK current inhibition could also be induced by repetitive GABAergic
      transmission at frequencies higher than the basal autorhythmic discharge of Golgi
      cells. These results suggest therefore that GABA(B) receptors can exert an
      inhibitory control over CIRK currents mediated by Kir2 channels. CIRK inhibition
      was associated with an increased input resistance around rest and caused a
      approximately 5 mV membrane depolarization. The pro-excitatory action of these
      effects at an inhibitory synapse may have an homeostatic role re-establishing
      granule cell readiness under conditions of strong inhibition.

PMID- 16903851
TI  - Inhibition of BK channel activity by association with calcineurin in rat brain.
AB  - Large conductance calcium-activated potassium (BK(Ca)) channels are regulated by
      a number of different protein kinases and phosphatases. The close association of
      enzymes and channel have been shown to underlie many examples of modulation.
      However, only the association of protein kinase A with the BK(Ca) channel has
      been detailed [Tian et al. (2003)J. Biol. Chem., 278, 8669-8677]. We have found
      using reciprocal immunoprecipitations that the BK(Ca) channel associates with the
      calcium/calmodulin-dependent phosphatase calcineurin, in Wistar rat brain. A HA
      tagged construct of the carboxyl terminus of rSlo(27), a variant of the BK(Ca)
      channel that is abundant in the hippocampus [Ha et al. (2000)Eur. J. Biochem.,
      267, 910-9218], was found to associate only with the B subunit of calcineurin.
      This data suggests that the majority of the interaction of the BK(Ca) channel
      with calcineurin is mediated by the B subunit of the phosphatase. This was
      confirmed by using glutathione-S-transferase (GST) fusion proteins of the linker
      regions between the S7-S10 hydrophobic domains in the carboxyl terminus of
      rSlo(27), where only the B subunit of calcineurin interacted with regions between
      S7 and S9 of the channel. Addition of a constitutively active calcineurin
      (CaN(420)) to inside-out membrane patches excised from cultured hippocampal
      neurons resulted in a dramatic reduction in BK(Ca) channel open probability, with
      only very short-duration events being apparent. These data suggest that BK(Ca)
      channel activity is inhibited by calcineurin, an effect mediated by the
      association of the calcineurin B subunit with the carboxyl terminus of the
      channel.

PMID- 16903852
TI  - Immunolocalization of BK channels in hippocampal pyramidal neurons.
AB  - Neurons are highly specialized cells in which the integration and processing of
      electrical signals critically depends on the precise localization of ion
      channels. For large-conductance Ca(2+)- activated K(+) (BK) channels, targeting
      to presynaptic membranes in hippocampal pyramidal cells was reported; however,
      functional evidence also suggests a somatodendritic localization. Therefore we re
      examined the subcellular distribution of BK channels in mouse hippocampus using a
      panel of independent antibodies in a combined approach of conventional
      immunocytochemistry on cultured neurons, pre- and postembedding electron
      microscopy and immunoprecipitation. In cultured murine hippocampal neurons, the
      colocalization of BK channels with both pre- and postsynaptic marker proteins was
      observed. Electron microscopy confirmed targeting of BK channels to axonal as
      well as dendritic membranes of glutamatergic synapses in hippocampus. A
      postsynaptic localization of BK channels was also supported by the finding that
      the channel coimmunoprecipitated with PSD95, a protein solely expressed in the
      postsynaptic compartment. These results thus demonstrate that BK channels reside
      in both post- and presynaptic compartments of hippocampal pyramidal neurons.

PMID- 16903853
TI  - Functional screening of traditional antidepressants with primary cortical
      neuronal networks grown on multielectrode neurochips.
AB  - We optimized the novel technique of multielectrode neurochip recordings for the
      rapid and efficient screening of neuroactivity. Changes in the spontaneous
      activity of cultured networks of primary cortical neurons were quantified to
      evaluate the action of drugs on the firing dynamics of complex network activity.
      The multiparametric assessment of electrical activity changes caused by
      psychoactive herbal extracts from Hypericum, Passiflora and Valeriana, and
      various combinations thereof revealed a receptor-specific and concentration
      dependent inhibition of the firing patterns. The spike and burst rates showed
      significant substance-dependent effects and significant differences in potency.
      The effects of specific receptor blockades on the inhibitory responses provided
      evidence that the herbal extracts act on gamma-amino butyric acid (GABA) and
      serotonin (5-HT) receptors, which are recognized targets of pharmacological
      antidepressant treatment. A biphasic effect, serotonergic stimulation of activity
      at low concentrations that is overridden by GABAergic inhibition at higher
      concentrations, is apparent with Hypericum alone and the triple combination of
      the extracts. The more potent neuroactivity of the triple combination compared to
      Hypericum alone and the additive effect of Passiflora and Valeriana suggest a
      synergy between constituent herbal extracts. The extracts and their combinations
      affected the set of derived activity parameters in a concomitant manner
      suggesting that all three constituent extracts and their combinations have
      largely similar modes of action. This study also demonstrates the sensitivity,
      selectivity and robustness of neurochip recordings for high content screening of
      complex mixtures of neuroactive substances and for providing multiparametric
      information on neuronal activity changes to assess the therapeutic potential of
      psychoactive substances.

PMID- 16903854
TI  - Postnatal development of the murine cerebellar cortex: formation and early
      dispersal of basket, stellate and Golgi neurons.
AB  - The cerebellar cortex consists of a small set of neuronal cell types
      interconnected in a highly stereotyped way. While the development of cerebellar
      cortical projection neurons, i.e. Purkinje cells, and that of granule cells has
      been elucidated in considerable detail, that of cerebellar cortical inhibitory
      interneurons is still rather fragmentarily understood. Here, we use mice
      expressing green fluorescent protein (GFP) from the Pax2 locus to analyse the
      ontogenesis of these cells. Numbers of Pax2-positive inhibitory interneuronal
      precursors increase following a classical sigmoidal growth curve to yield a total
      of some 905.000 +/- 77.000 cells. Maximal cell increase occurs at about postnatal
      day (P)5.4, and some 75% of all inhibitory interneurons are generated prior to
      P7. Conjoint analysis of the developmental accruement of Pax2-GFP-positive cells
      and their cell cycle distribution reveals that, at least at P0 and P3, the
      numerical increase of these cells results primarily from proliferation of a Pax2
      negative precursor population and suggests that Pax2 expression begins at or
      around the final mitosis. Following their terminal mitosis, inhibitory cerebellar
      cortical interneurons go through a protracted quiescent phase in which they
      maintain expression of the cell cycle marker Ki-67. During this phase, they
      translocate into the nascent molecular layer, where they stall next to
      premigratory granule cell precursors without penetrating this population of
      cells. These observations provide a quantitative description of cerebellar
      cortical inhibitory interneuron genesis and early differentiation, and define
      Pax2 as a marker expressed in basket and stellate cells, from around their final
      mitosis to their incipient histogenetic integration.

PMID- 16903855
TI  - Galanin-neuropeptide Y (NPY) interactions in central cardiovascular control:
      involvement of the NPY Y receptor subtype.
AB  - The interactions between neuropeptide Y (NPY), specifically through NPY Y(1) and
      Y(2) receptor subtypes, and galanin [GAL(1-29)] have been analysed at the
      cardiovascular level. The cardiovascular effects of intracisternal coinjections
      of GAL(1-29) with NPY or NPY Y(1) or Y(2) agonists, as well as quantitative
      receptor autoradiography of the binding characteristics of NPY Y(1) and Y(2)
      receptor subtypes in the nucleus of the solitary tract (NTS), in the presence or
      absence of GAL(1-29), have been investigated. The effects of coinjections of
      GAL(1-29) and the NPY Y(1) agonist on the expression of c-FOS immunoreactivity in
      the NTS were also studied. The coinjection of NPY with GAL(1-29) induced a
      significant vasopressor and tachycardic action with a maximum 40% increase (P <
      0.001). The coinjection of the NPY Y(1) agonist and GAL(1-29) induced a similar
      increase in mean arterial pressure and heart rate as did NPY plus GAL(1-29),
      actions that were not observed with the NPY Y(2) agonist plus GAL(1-29). GAL(1
      29), 3 nm, significantly and substantially (by approximately 40%) decreased NPY
      Y(1) agonist binding in the NTS. This effect was significantly blocked (P < 0.01)
      in the presence of the specific galanin antagonist M35. The NPY Y(2) agonist
      binding was not modified in the presence of GAL(1-29). At the c-FOS level, the
      coinjection of NPY Y(1) and GAL(1-29) significantly reduced the c-FOS
      immunoreactive response induced by either of the two peptides. The present
      findings suggest the existence of a modulatory antagonistic effect of GAL(1-29)
      mediated via galanin receptors on the NPY Y(1) receptor subtype and its
      signalling within the NTS.

PMID- 16903856
TI  - Early life modulators and predictors of adult synaptic plasticity.
AB  - Early life experience can induce long-lasting changes in brain and behaviour that
      are opposite in direction, such as enhancement or impairment in regulation of
      stress response, structural and functional integrity of the hippocampus, and
      learning and memory. To explore how multiple early life events jointly determine
      developmental outcome, we investigated the combined effects of neonatal trauma
      (anoxia on postnatal day 1, P1) and neonatal novelty exposure (P2-21) on adult
      social recognition memory (3 months of age) and synaptic plasticity in the CA1 of
      the rat hippocampus (4.5-8 months of age). While neonatal anoxia selectively
      reduced post-tetanic potentiation (PTP), neonatal novel exposure selectively
      increased long-term potentiation (LTP). No interaction between anoxia and novelty
      exposure was found on either PTP or LTP. These findings suggest that the two
      contrasting neonatal events have selective and distinct effects on two different
      forms of synaptic plasticity. At the level of behaviour, the effect of novelty
      exposure on LTP was associated with increased social memory, and the effect of
      anoxia on PTP was not accompanied by changes in social memory. Such a finding
      suggests a bias toward the involvement of LTP over PTP in social memory. Finally,
      we report a surprising finding that an early behavioural measure of emotional
      response to a novel environment obtained at 25 days of age can predict adult LTP
      measured several months later. Therefore, individual differences in emotional
      responses present during the juvenile stage may contribute to adult individual
      differences in cellular mechanisms that underlie learning and memory.

PMID- 16903857
TI  - Long-term depression activates transcription of immediate early transcription
      factor genes: involvement of serum response factor/Elk-1.
AB  - Long-term depression (LTD) is one of the paradigms used in vivo or ex vivo for
      studying memory formation. In order to identify genes with potential relevance
      for memory formation we used mouse organotypic hippocampal slice cultures in
      which chemical LTD was induced by applications of 3,5-dihydroxyphenylglycine
      (DHPG). The induction of chemical LTD was robust, as monitored
      electrophysiologically. Gene expression analysis after chemical LTD induction was
      performed using cDNA microarrays containing >7,000 probes. The DHPG-induced
      expression of immediate early genes (c-fos, junB, egr1 and nr4a1) was
      subsequently verified by TaqMan polymerase chain reaction. Bioinformatic analysis
      suggested a common regulator element [serum response factor (SRF)/Elk-1 binding
      sites] within the promoter region of these genes. Indeed, here we could show a
      DHPG-dependent binding of SRF at the SRF response element (SRE) site within the
      promoter region of c-fos and junB. However, SRF binding to egr1 promoter sites
      was constitutive. The phosphorylation of the ternary complex factor Elk-1 and its
      localization in the nucleus of hippocampal neurones after DHPG treatment was
      shown by immunofluorescence using a phosphospecific antibody. We suggest that LTD
      leads to SRF/Elk-1-regulated gene expression of immediate early transcription
      factors, which could in turn promote a second broader wave of gene expression.

PMID- 16903858
TI  - Partial inhibition of PP1 alters bidirectional synaptic plasticity in the
      hippocampus.
AB  - Synaptic plasticity is an important cellular mechanism that underlies memory
      formation. In brain areas involved in memory such as the hippocampus, long-term
      synaptic plasticity is bidirectional. Major forms of bidirectional plasticity
      encompass long-term potentiation (LTP), LTP reversal (depotentiation) and long
      term depression (LTD). Protein kinases and protein phosphatases are important
      players in the induction of both LTP and LTD, and the serine/threonine protein
      phosphatase-1 (PP1), in particular, has emerged as a key phosphatase in these
      processes. The goal of the present study was to assess the contribution of PP1 to
      bidirectional plasticity and examine the impact of a partial inhibition of PP1 on
      LTP, LTD and depotentiation in the mouse hippocampus. For this, we used
      transgenic mice expressing an active PP1 inhibitor (I-1*) inducibly in forebrain
      neurons. We show that partial inhibition of PP1 by I-1* expression alters the
      properties of bidirectional plasticity by inducing a shift of synaptic responses
      towards potentiation. At low-frequency stimulation, PP1 inhibition decreases LTD
      in a frequency-dependent fashion. It favours potentiation over depression at
      intermediate frequencies and increases LTP at high frequency. Consistently, it
      also impairs depotentiation. These results indicate that the requirement of
      bidirectional plasticity for PP1 is frequency-dependent and that a broad range of
      plasticity is negatively constrained by PP1, a feature that may correlate with
      the property of PP1 to constrain learning efficacy and promote forgetting.

PMID- 16903859
TI  - Apoptosis in the rat basal forebrain during development and following lesions of
      connections.
AB  - Evidence suggests that neurotrophins are essential for the survival and
      phenotypic maintenance of cholinergic basal forebrain (BF) neurons. We evaluated
      the pattern of programmed cell death in the BF of the rat during development and
      after ablations of the cerebral cortex, a major target area and source of
      neurotrophins for BF neurons. We identified dying cells using the TUNEL (terminal
      deoxynucleotidyl-transferase-mediated dUTP-biotin nick end labelling) method and
      confirmed their apoptotic morphology with electron microscopy. Moreover, we
      demonstrated the expression of the apoptotic marker active caspase-3 in cells
      with features of apoptosis. TUNEL(+) cells were present in the developing BF
      during the first two postnatal weeks. Their frequency peaked at postnatal day
      (P)1 and at P5. TUNEL used in conjunction with immunofluorescence for neuronal
      nuclear protein (NeuN) showed that, at both peak stages, the majority of
      apoptotic cells were neurons. Extensive lesions of the cerebral cortex at
      different ages (P0, P7 and P14) did not induce significant changes in the
      frequency of apoptotic BF neurons. However, they resulted in alterations in the
      morphological phenotype of choline acetyltransferase (ChAT)-immunoreactive
      neurons in the BF, and a reduction in their number which was inversely
      proportional to the age at which the lesions were performed. We suggest that: (i)
      apoptosis is temporally coordinated with the morphological and neurochemical
      differentiation of BF neurons and the establishment of connections with their
      target areas; and (ii) cortical ablations do not affect the survival of BF
      neurons, but they influence the phenotype of cholinergic BF neurons.

PMID- 16903860
TI  - Chronic cocaine exposure impairs progenitor proliferation but spares survival and
      maturation of neural precursors in adult rat dentate gyrus.
AB  - Recent observations indicate that drugs of abuse, including alcohol and opiates,
      impair adult neurogenesis in the hippocampus. We have studied in rats the impact
      of cocaine treatment (20 mg/kg, daily, i.p.) on cell proliferation, survival and
      maturation following short-term (8-day) and long-term (24-day) exposure. Using 5'
      bromo-2-deoxyuridine (BrdU) and Ki-67 as mitotic markers at the end of the drug
      treatments, we found that both short- and long-term cocaine exposures
      significantly reduced cell proliferation in the dentate gyrus (DG) of the
      hippocampus. By labelling mitotic cells with BrdU pulses before or during the
      early stages of the drug treatment, we determined that long-term cocaine exposure
      did not affect the survival of newly generated cells. In register with this
      finding, cocaine chronic exposure did not increase the number of apoptotic cells
      labelled by TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end
      labelling). Using doublecortin (DCX) immunocytochemistry and electron microscopy,
      we next examined the effects of cocaine exposure on the maturation of the neural
      precursors and on synaptic output to CA3. DCX immunocytochemistry showed that
      immature hippocampal cells of rats exposed to cocaine displayed normal
      arborization patterns and similar degrees of colocalization with BrdU at two
      different developmental stages. Moreover, cocaine did not produce significant
      morphological alterations of the mossy fibre projection system to stratum lucidum
      in the CA3 area of the hippocampus. The results presented demonstrate that
      chronic cocaine exposure impairs proliferation dynamics in the DG without
      significantly altering either the survival and growth of immature cells or the
      structural features of terminal projections to CA3.

PMID- 16903862
TI  - A context-specific single contingent-reinforcing stimulus boosts intermediate
      term memory into long-term memory.
AB  - Following operant conditioning of aerial respiration in Lymnaea, memory forms.
      Depending on the training procedure either intermediate memory (ITM, < 3 h) or
      long-term memory (LTM, > 6 h) results. ITM is dependent on de novo protein
      synthesis whilst LTM is dependent on both transcription and de novo protein
      synthesis. LTM formation requires the soma of RPeD1 (one of the central pattern
      generator neurons) to be present. Following activation of a memory, it re-enters
      a labile state and undergoes a reconsolidation process to restabilize it. During
      reconsolidation, memory may be updated and/or changed. We add here another
      consequence of memory reactivation: a single contingent-reinforcing stimulus
      (SCRS), given in the same context as previous ITM training, boosts a residual
      memory trace to LTM. Separate cohorts of snails first received the ITM training
      procedure. In the cohort that received the SCRS 24 h after the last ITM training
      session, LTM was observed on the following day. LTM was not observed in cohorts
      that were: (i) given a single noncontingent stimulus; (ii) given the SCRS in a
      context other than the ITM training; (iii) given a 48-h gap between the last ITM
      training session and the context-specific SCRS; (iv) cooled immediately after the
      last ITM training session; (v) cooled immediately after the delivery of the
      context-specific SCRS; (vi) had the soma of RPeD1 ablated before the presentation
      of the context-specific SCRS; (vii) received a yoked control procedure. These
      data lead us to conclude that the context-specific SCRS reactivates a residual
      molecular memory trace in RPeD1 and boosts it into becoming the substrate for
      LTM.

PMID- 16903861
TI  - Attenuating corticosterone levels on the day of memory assessment prevents
      chronic stress-induced impairments in spatial memory.
AB  - This study investigated whether chronic stress-induced spatial memory deficits
      were caused by changes in the hypothalamic-pituitary-adrenal axis, such as
      corticosterone (CORT) elevations on the day of memory assessment, rather than the
      consequence of structural changes in the hippocampus. Male Sprague-Dawley rats
      were restrained for 6 h/day/21 days, and spatial memory was assessed on the Y
      maze on day 22. Ninety minutes before training, rats received a subcutaneous
      injection of vehicle or metyrapone, a CORT synthesis inhibitor, and then spatial
      memory was determined 4-h later. The highest dose of metyrapone (75 mg/kg, s.c.)
      was most effective at preventing stress-induced spatial memory deficits. Chronic
      stress increased total CORT levels following Y-maze exposure, while acute
      metyrapone treatment dose-dependently attenuated total and free (unbound) CORT
      levels in both stress and control conditions. Blood samples taken from a separate
      subset of chronically stressed rats showed that baseline CORT levels were similar
      across the restraint period. Finally, chronic stress down-regulated
      glucocorticoid, but not mineralocorticoid, receptor mRNA expression within the
      hippocampus (dentate gyrus, CA1, CA2, CA3). These findings suggest that chronic
      stress-induced spatial memory deficits may be mediated by hypothalamic-pituitary
      adrenal axis dysregulation. Specifically, CORT elevations and reductions in
      hippocampal glucocorticoid receptor expression, at the time of behavioural
      assessment may be involved, as opposed to a direct effect that is solely
      dependent upon hippocampal structural changes. These results have significance
      for treating cognitive decline in conditions associated with elevated
      glucocorticoids that include subpopulations in ageing, depression, Cushing's
      disease and Alzheimer's disease.

PMID- 16903863
TI  - Partial depletion of dopamine in substantia nigra impairs motor performance
      without altering striatal dopamine neurotransmission.
AB  - Previous data indicate that the release of somatodendritic dopamine in substantia
      nigra influences motor activity and coordination, but the relative importance of
      somatodendritic dopamine release vs. terminal striatal dopamine release remains
      to be determined. We utilized simultaneous measurement of dopamine
      neurotransmission by microdialysis and motor performance assessment by rotarod
      test to investigate the effects of local dopamine depletion in rats. The
      vesicular monoamine transporter inhibitor tetrabenazine (100 microm) was
      administered locally in substantia nigra as well as in striatum. Nigral
      tetrabenazine administration decreased nigral dopamine dialysate concentrations
      to 7% of baseline and whole-tissue dopamine content by 60%. Nigral dopamine
      depletion was associated with a reduction in motor performance to 73 +/- 6% of
      pretreatment value, but did not alter dialysate dopamine concentrations in the
      ipsilateral striatum. Striatal tetrabenazine administration decreased striatal
      dopamine dialysate concentrations to 5% of baseline and doubled the
      somatodendritic dopamine response to motor activity, but it was not associated
      with changes in motor performance or dopamine content in striatal tissue.
      Simultaneous treatment of substantia nigra and striatum reduced motor performance
      to 58 +/- 5% of the pretreatment value. The results of this study indicate that
      partial depletion of nigral dopamine stores can significantly impair motor
      functions, and that increased nigral dopamine release can counteract minor
      impairments of striatal dopamine transmission.

PMID- 16903864
TI  - Limb (hand vs. foot) and response conflict have similar effects on event-related
      potentials (ERPs) recorded during motor imagery and overt execution.
AB  - Although there is substantial evidence that motor execution (M-Ex) and motor
      imagery (M-Im) share a common neural substrate, the role of the primary motor
      cortex (M1) during imagery is still a matter of debate. The present ERP study
      tries to clarify the functional similarity between the two processes in respect
      of (i) the engagement of the corresponding somatotopic M1 areas during execution
      and imagery of hand vs. foot movements; and (ii) the effect of conflicting
      information on response preparation. To this end, we recorded ERPs from 28
      electrode sites in 19 participants while they performed a conflict task with
      congruent (target and flanker arrowheads pointing in the same direction) and
      incongruent (target pointing in the opposite direction to the flanker arrowheads)
      trials. We obtained the lateralized readiness potential (LRP), a component
      generated in M1, while subjects physically executed or mentally simulated the
      task. As expected by the somatotopic organization of M1, the LRP was of opposite
      polarity when foot, rather than hand, movements were prepared. The inversion of
      polarity also occurred during M-Im, a result that strongly argues in favour of
      the participation of M1 in motor imagery. In incongruent trials, longer LRP
      latencies, a premature preparation of the incorrect response (positive deflection
      in LRP waveform) and a fronto-central N2 component associated with response
      conflict appeared during both M-Ex and M-Im. Altogether, the results support the
      functional equivalence of the two processes and give support to the clinical use
      of M-Im for the improvement and recovery of motor functions.

PMID- 16903865
TI  - Oligomerization of the Mg2+-transport proteins Alr1p and Alr2p in yeast plasma
      membrane.
AB  - Alr1p is an integral plasma membrane protein essential for uptake of Mg(2+) into
      yeast cells. Homologs of Alr1p are restricted to fungi and some protozoa. Alr1
      type proteins are distant relatives of the mitochondrial and bacterial Mg(2+)
      transport proteins, Mrs2p and CorA, respectively, with which they have two
      adjacent TM domains and a short Mg(2+) signature motif in common. The yeast
      genome encodes a close homolog of Alr1p, named Alr2p. Both proteins are shown
      here to be present in the plasma membrane. Alr2p contributes poorly to Mg(2+)
      uptake. Substitution of a single arginine with a glutamic acid residue in the
      loop connecting the two TM domains at the cell surface greatly improves its
      function. Both proteins are shown to form homo-oligomers as well as hetero
      oligomers. Wild-type Alr2p and mutant Alr1 proteins can have dominant-negative
      effects on wild-type Alr1p activity, presumably through oligomerization of low
      function with full-function proteins. Chemical cross-linking indicates the
      presence of Alr1 oligomers, and split-ubiquitin assays reveal Alr1p-Alr1p, Alr2p
      Alr2p, and Alr1p-Alr2p interactions. These assays also show that both the N
      terminus and C-terminus of Alr1p and Alr2p are exposed to the inner side of the
      plasma membrane.

PMID- 16903866
TI  - Suppression of microtubule dynamics by benomyl decreases tension across
      kinetochore pairs and induces apoptosis in cancer cells.
AB  - We found that benomyl, a benzimidazole fungicide, strongly suppressed the
      reassembly of cold-depolymerized spindle microtubules in HeLa cells. Benomyl
      perturbed microtubule-kinetochore attachment and chromosome alignment at the
      metaphase plate. Benomyl also significantly decreased the distance between the
      sister kinetochore pairs in metaphase cells and increased the level of the
      checkpoint protein BubR1 at the kinetochore region, indicating that benomyl
      caused loss of tension across the kinetochores. In addition, benomyl decreased
      the intercentrosomal distance in mitotic HeLa cells and blocked the cells at
      mitosis. Further, we analyzed the effects of benomyl on the signal transduction
      pathways in relation to mitotic block, bcl2 phosphorylation and induction of
      apoptosis. The results suggest that benomyl causes loss of tension across the
      kinetochores, blocks the cell cycle progression at mitosis and subsequently,
      induces apoptosis through the bcl2-bax pathway in a manner qualitatively similar
      to the powerful microtubule targeted anticancer drugs like the vinca alkaloids
      and paclitaxel. Considering the very high toxicity of the potent anticancer drugs
      and the low toxicity of benomyl in humans, we suggest that benomyl could be
      useful as an adjuvant in combination with the powerful anticancer drugs in cancer
      therapy.

PMID- 16903867
TI  - Large-scale expansion of rat CD4+ CD25+ T(reg) cells in the absence of T-cell
      receptor stimulation.
AB  - T-cell receptor (TCR) stimulation is both central to homeostatic maintenance of
      CD4(+) CD25(+) regulatory T cells (T(reg) cells) in vivo and a prerequisite for
      the initiation of suppression by T(reg) cells, both in vivo and in vitro.
      However, TCR-independent stimulation of T(reg) cells, e.g. with superagonistic
      CD28-specific monoclonal antibodies (CD28-SA), not only expands these cells in
      vivo but, as we show here, also mediates large-scale expansion of rat T(reg)
      cells in vitro. Interestingly, CD28-SA stimulation plus interleukin (IL)-2 was
      even superior to conventional costimulation plus IL-2 in promoting T(reg) cell
      growth in vitro. Despite their highly activated phenotype suppression by T(reg)
      cells expanded in the absence of TCR stimulation remained fully dependent on TCR
      triggering for initiation and cell contact was required to exert suppression.
      With regard to the regulation of suppression by CD28 stimulation we observed that
      neither the presence of a conventional anti-CD28 monoclonal antibody nor a CD28
      SA generally rendered conventional T cells resistant to suppression by
      preactivated T(reg) cells. Taken together, we provide a novel protocol for long
      term propagation of T(reg) cells in vitro and our data are the first to reveal a
      difference in the signals required for activation and expansion of T(reg) cells
      and those, involving the TCR, necessary for the initiation of suppression.

PMID- 16903868
TI  - Enhanced neutrophil motility by granulocyte colony-stimulating factor: the role
      of extracellular signal-regulated kinase and phosphatidylinositol 3-kinase.
AB  - The effect of granulocyte colony-stimulating factor (G-CSF) on human neutrophil
      motility was studied using videomicroscopy. Stimulation of neutrophils with G-CSF
      resulted in enhanced motility with morphological change and increased adherence.
      Enhanced neutrophil motility was detected within 3-5 min after G-CSF stimulation,
      reached a maximum at 10 min, and was sustained for approximately 35 min. The
      maximum migration rate was 84.4 +/- 2.9 microm/5 min. A study using the Boyden
      chamber method revealed that G-CSF-stimulated neutrophils exhibited random
      migration but not chemotaxis. Enhanced neutrophil motility and morphological
      change were inhibited by MEK [mitogen-activated protein kinase
      (MAPK)/extracellular signal-regulated kinase (ERK) kinase] inhibitors (PD98059
      and U0126), and a phosphatidylinositol 3-kinase (PI3K) inhibitor (wortmannin),
      but not by a p38 MAPK inhibitor (SB203580). These findings are consistent with
      the fact that G-CSF selectively activates MEK/ERK and PI3K, but not p38, in
      neutrophils. MEK/ERK activation was associated with G-CSF-induced redistribution
      of F-actin and phosphorylated myosin light chain. Enhanced neutrophil motility
      was observed even in the presence of neutralizing anti-CD18 antibody, which
      prevented cell adherence. These findings indicate that G-CSF induces human
      neutrophil migration via activation of MEK/ERK and PI3K.

PMID- 16903869
TI  - Kanamycin alters cytoplasmic and nuclear phosphoinositide signaling in the organ
      of Corti in vivo.
AB  - Aminoglycoside antibiotics strongly bind to phosphoinositides and affect their
      membrane distribution and metabolism. Kanamycin treatment also disrupts Rac/Rho
      signaling pathways to the actin cytoskeleton in the mouse inner ear in vivo.
      Here, we investigate the influence of kanamycin on phosphoinositide signaling in
      sensory cells (hair cells) of the mouse cochlea. Immunoreactivity to
      phosphatidylinositol-3,4,5-trisphosphate (PIP3) decreased in the organ of Corti,
      especially in outer hair cells, after 3-7 days of drug treatment, whereas
      imunoreactivity to phosphatidylinositol-4,5-bisphosphate (PIP2) increased.
      Immunoreactivity to PIP2 was present at the apical poles of outer hair cells, but
      appeared in their nuclei only after drug treatment. Furthermore, nuclear PIP2
      formed a complex with histone H3 and attenuated its acetylation in outer hair
      cells. In agreement with reduced PIP3 signaling, phosphorylated Akt decreased in
      both the cytoplasm and nuclei of outer hair cells after kanamycin treatment. This
      study suggests that kanamycin disturbs the balance between PIP2 and PIP3,
      modifies gene transcription via histone acetylation and diminishes the PI3K/Akt
      survival pathway. These actions may contribute to the death of outer hair cells,
      which is a consequence of chronic kanamycin treatment.

PMID- 16903870
TI  - Polysialic acid limits choline acetyltransferase activity induced by brain
      derived neurotrophic factor.
AB  - Choline acetyltransferase (ChAT), the enzyme synthesizing acetylcholine, is known
      to be activated by brain derived neurotrophic factor (BDNF). We found that the
      specific removal of the carbohydrate polysialic acid (PSA) significantly
      increased BDNF-induced ChAT-activity in embryonic septal neurons. Using a p75
      neurotrophin receptor (p75(NTR)) function-blocking antibody and K252a, a-pan
      tropomyosin related kinase (Trk) inhibitor, we demonstrate that BDNF-induced ChAT
      activity requires the stimulation of p75(NTR) and TrkB. PSA removal drastically
      increased radioactive iodinated ([(125)I])BDNF's maximal binding capacity (Bmax),
      derived from concentrations of [(125)I]BDNF ranging from 1 pM to 3.2 nM. In the
      presence of unlabeled nerve growth factor to prevent the binding of [(125)I]BDNF
      to p75(NTR) sites, the impact of PSA removal on the binding capacity of
      [(125)I]BDNF was greatly reduced. In conclusion, PSA limits BDNF-induced ChAT
      activity and BDNF-receptor interactions. BDNF-induced ChAT activity is TrkB and
      p75(NTR) dependent, and upon PSA removal the additional binding of BDNF to its
      receptors, especially p75(NTR), likely contributes to the maximal ChAT activity
      observed. In vivo, the ontogenetic loss of PSA in the postnatal period may allow
      more interactions between BDNF and its receptors to increase ChAT activity and
      assure the proper development of the cholinergic septal neurons.

PMID- 16903871
TI  - Sustained brain-derived neurotrophic factor up-regulation and sensorimotor gating
      abnormality induced by postnatal exposure to phencyclidine: comparison with adult
      treatment.
AB  - Brain-derived neurotrophic factor (BDNF) is involved in synaptic development and
      plasticity, and alterations in BDNF expression or signaling are implicated in
      drug addiction and psychiatric diseases, such as depression and schizophrenia. In
      this study, we administered phencyclidine to postnatal and adult rats with
      different time schedules, and determined the correlations between BDNF expression
      and the behavioral effects. Both single and repeated phencyclidine injections
      into adult rats induced BDNF up-regulation in the corticolimbic system and a
      decrease in prepulse inhibition, both of which were transient. In contrast,
      subchronic postnatal administration increased BDNF protein and mRNA levels in the
      hippocampus and entorhinal cortex, which were sustained until 8 weeks of age. In
      parallel, the postnatal rats treated with phencyclidine developed a persistent
      decrease in prepulse inhibition at the adult stage. The chronic BDNF increase
      appeared to contribute to the prepulse inhibition abnormality, as subchronic BDNF
      infusion into the hippocampus of normal rats mimicked the prepulse inhibition
      deficits. This study suggests that phencyclidine exposure during brain
      development induces sustained BDNF up-regulation in the limbic system with a
      biological link to sensorimotor gating deficits.

PMID- 16903872
TI  - Mesotrypsin, a brain trypsin, activates selectively proteinase-activated receptor
      1, but not proteinase-activated receptor-2, in rat astrocytes.
AB  - Proteinase-activated receptors (PARs), a subfamily of G protein-coupled
      receptors, which are activated by serine proteases, such as trypsin, play pivotal
      roles in the CNS. Mesotrypsin (trypsin IV) has been identified as a brain
      specific trypsin isoform. However, its potential physiological role concerning
      PAR activation in the brain is largely unknown. Here, we show for the first time
      that mesotrypsin, encoded by the PRSS3 (proteinase, serine) gene, evokes a
      transient and pronounced Ca(2+) mobilization in both primary rat astrocytes and
      retinal ganglion RGC-5 cells, suggesting a physiological role of mesotrypsin in
      brain cells. Mesotrypsin mediates Ca(2+) responses in rat astrocytes in a
      concentration-dependent manner, with a 50% effective concentration (EC(50)) value
      of 25 nm. The maximal effect of mesotrypsin on Ca(2+) mobilization in rat
      astrocytes is much higher than that observed in 1321N1 human astrocytoma cells,
      indicating that the activity of mesotrypsin is species-specific. The pre
      treatment of cells with thrombin or the PAR-1-specific peptide TRag (Ala-pFluoro
      Phe-Arg-Cha-HomoArg-Tyr-NH(2), synthetic thrombin receptor agonist peptide), but
      not the PAR-2-specific peptide, reduces significantly the mesotrypsin-induced
      Ca(2+) response. Treatment with the PAR-1 antagonist SCH79797 confirms that
      mesotrypsin selectively activates PAR-1 in rat astrocytes. Unlike mesotrypsin,
      the two other trypsin isoforms, cationic and anionic trypsin, activate multiple
      PARs in rat astrocytes. Therefore, our data suggest that brain-specific
      mesotrypsin, via the regulation of PAR-1, is likely to be involved in multiple
      physiological/pathological processes in the brain.

PMID- 16903874
TI  - The role of prohormone convertase-2 in hypothalamic neuropeptide processing: a
      quantitative neuropeptidomic study.
AB  - Prohormone convertase (PC) 1/3 and 2 are involved in the generation of
      neuropeptides from their precursors. A quantitative peptidomic approach was used
      to explore the role PC2 plays in the processing of hypothalamic peptides. In this
      approach, extracts from mice lacking PC2 activity and from wild-type littermates
      were labeled with isotopic tags, combined, fractionated on a reverse phase HPLC
      column, and analyzed by electrospray ionization mass spectrometry. Altogether, 53
      neuropeptides or other peptides derived from secretory pathway proteins were
      identified and sequenced using tandem mass spectrometry. These peptides arise
      from 21 distinct proteins: proenkephalin, proopiomelanocortin, prodynorphin,
      protachykinin A and B, procholecystokinin, promelanin-concentrating hormone,
      proneurotensin, proneuropeptide Y, provasopressin, pronociceptin/orphanin,
      prothyrotropin-releasing hormone, cocaine- and amphetamine-regulated transcript,
      chromogranin A and B, secretogranin II, prohormone convertase 1 and 2,
      propeptidyl-amidating monooxygenase, and proteins designated proSAAS and VGF.
      Approximately one third of the peptides found in wild-type mice were not
      detectable in PC2 knock-out mice, and another third were present at levels
      ranging from 25 to 75% of wild-type levels. Comparison of the cleavage sites
      suggests that sequences with a Trp, Tyr and/or Pro in the P1' or P2' position, or
      a basic residue in the P3 position, are preferentially cleaved by PC2 and not by
      other enzymes present in the secretory pathway.

PMID- 16903873
TI  - Ultrastructural localisation and differential agonist-induced regulation of AMPA
      and kainate receptors present at the presynaptic active zone and postsynaptic
      density.
AB  - Activity-dependent changes in ionotropic glutamate receptors at the postsynaptic
      membrane are well established and this regulation plays a central role in the
      expression of synaptic plasticity. However, very little is known about the
      distributions and regulation of ionotropic receptors at presynaptic sites. To
      determine if presynaptic receptors are subject to similar regulatory processes we
      investigated the localisation and modulation of AMPA (GluR1, GluR2, GluR3) and
      kainate (GluR6/7, KA2) receptor subunits by ultrasynaptic separation and
      immunoblot analysis of rat brain synaptosomes. All of the subunits were enriched
      in the postsynaptic fraction but were also present in the presynaptic and non
      synaptic synaptosome fractions. AMPA stimulation resulted in a marked decrease in
      postsynaptic GluR2 and GluR3 subunits, but an increase in GluR6/7. Conversely,
      GluR2 and GluR3 increased in the presynaptic fraction whereas GluR6/7 decreased.
      There were no significant changes in any of the compartments for GluR1. NMDA
      treatment decreased postsynaptic GluR1, GluR2 and GluR6/7 but increased
      presynaptic levels of these subunits. NMDA treatment did not evoke changes in
      GluR3 localisation. Our results demonstrate that presynaptic and postsynaptic
      subunits are regulated in opposite directions by AMPA and NMDA stimulation.

PMID- 16903876
TI  - Complex alternative splicing of the myelin oligodendrocyte glycoprotein gene is
      unique to human and non-human primates.
AB  - Myelin/oligodendrocyte glycoprotein (MOG) is a minor integral membrane protein
      specific to CNS myelin, encoded by a gene located in the major histocompatibility
      complex. MOG is an highly encephalitogenic autoantigen and a target for
      autoaggressive immune responses in CNS inflammatory demyelinating diseases. We
      performed transcriptomic analyses for a gene expressed only in mammalian CNS,
      myelin oligodendrocyte glycoprotein (MOG). Complex splicing patterns were
      exclusively found in primates and not in mice, unlike patterns found for other
      myelin protein genes. In addition to those shared with rodents, these multiple
      MOG isoforms likely support functions unique to the primate order, in particular
      maintenance of myelin structure, intracellular signaling, and modulation of CNS
      autoimmunity via exposure of specific MOG determinants. Developmentally, in human
      brain the splice variants of MOG appear at a late stage compared to the major
      isoform, coincidental with myelination and myelin maturation, unlike other myelin
      proteins. These findings are discussed within the framework of a biological basis
      for phenotype diversity in recent mammalian evolution and for the notoriously
      variable clinical expression of diseases such as multiple sclerosis.

PMID- 16903875
TI  - Blockade of PARP activity attenuates poly(ADP-ribosyl)ation but offers only
      partial neuroprotection against NMDA-induced cell death in the rat retina.
AB  - Recent reports have linked neuronal cell death by necrosis to poly(ADP-ribose)
      polymerase-1 (PARP-1) hyperactivation. It is believed that under stress, the
      activity of this enzyme is up-regulated, resulting in extensive poly(ADP
      ribosyl)ation of nuclear proteins, using NAD(+) as its substrate, which, in turn,
      leads to the depletion of NAD(+). In efforts to restore the level of NAD(+),
      depletion of ATP occurs, resulting in the shutdown of ATP-dependent ionic pumps.
      This results in cell swelling and eventual loss of membrane selectivity,
      hallmarks of necrosis. Reports from in vitro and in vivo studies in the brain
      have shown that NMDA receptor activation stimulates PARP activity and that
      blockade of the enzyme provides substantial neuroprotection. The present study
      was undertaken to determine whether PARP activity is regulated by NMDA in the rat
      retina, and whether blockade of PARP activity provides protection against toxic
      effects of NMDA. Rat retinas exposed to intravitreal injections containing NMDA,
      with or without the PARP inhibitor N-(6-oxo-5, 6-dihydrophenanthridin-2-yl)-(N,
      dimethylamino) acetamide hydrochloride (PJ-34), were assessed for changes in PARP
      1 activity as evidenced by poly(ADP-ribosyl)ation (PAR), loss of membrane
      integrity, morphological indicators of apoptosis and necrosis, and ganglion cell
      loss. Results showed that: NMDA increased PAR formation in a concentration
      dependent manner and caused a decline in retinal ATP levels; PJ-34 blockade
      attenuated the NMDA-induced formation of PAR and decline in ATP; NMDA induced the
      loss of membrane selectivity to ethidium bromide (EtBr) in inner retinal neurons,
      but loss of membrane selectivity was not prevented by blocking PARP activity;
      cells stained with EtBr, or reacted for TUNEL-labeling, displayed features
      characteristic of both apoptosis and necrosis. In the presence of PJ-34, greater
      numbers of cells exhibited apoptotic features; PJ-34 provided partial
      neuroprotection against NMDA-induced ganglion cell loss. These findings suggest
      that although blockade of PARP activity fully attenuates NMDA-induced PAR
      formation and loss of retinal ATP content, and improves the survival of select
      populations of ganglion cells, this approach does not provide full
      neuroprotection. In contrast, blockade of PARP activity promotes apoptotic-like
      cell death in the majority of cells undergoing cell death. Furthermore, these
      studies show that the loss of membrane selectivity is not dependent upon PAR
      formation or the resulting decline of ATP, and suggests that an alternative
      pathway, other than PARP activation, exists to mediate this event.

PMID- 16903877
TI  - Editorial: advancing the Mexico agenda for health systems research--from clinical
      efficacy to population health.

PMID- 16903878
TI  - Predictors of treatment error for children with uncomplicated malaria seen as
      outpatients in Blantyre district, Malawi.
AB  - BACKGROUND: Past studies have shown that health workers in developing countries
      often do not follow clinical guidelines, though few studies have explored with
      appropriate methods why errors occur. To develop interventions that improve
      health worker performance, factors affecting treatment practices must be better
      understood. METHODS: We analysed data from a health facility survey in Blantyre
      District, Malawi, in which health workers were observed treating ill children,
      and then children were independently re-examined by 'gold-standard' study
      clinicians. The analysis was limited to children with uncomplicated malaria
      (defined according to Malawi's guidelines as fever or anaemia without signs of
      severe illness), and a treatment error was defined as failure to treat with an
      effective antimalarial. RESULTS: Twenty-eight health workers and 349 ill-child
      consultations were evaluated; 247 (70.8%) children were treated with an effective
      antimalarial, and 102 (29.2%) were subject to treatment error. Logistic
      regression analysis revealed that in-service malaria training was not associated
      with treatment quality (univariate odds ratio (OR) = 1.16, 95% confidence
      interval (CI): 0.46-2.93); whereas acute respiratory infections training was
      associated with making an error (adjusted OR (aOR) = 2.42, 95% CI: 1.23-4.76).
      High fever and chief complaint of fever were associated with fewer errors (aOR =
      0.25, 95% CI: 0.10-0.60 and aOR = 0.25, 95% CI: 0.13-0.48, respectively). Errors
      were more likely to occur in consultations starting before 1 p.m. (aOR = 1.88,
      95% CI: 1.07-3.31). Supervision was not associated with better treatment quality.
      CONCLUSIONS: These results suggest that the disease-specific training and
      supervision, performed before the survey, did not lead to long-term improvements
      in health care quality. Furthermore, case management training for one specific
      disease may have worsened quality of care for another disease. These results
      support integration of guidelines for multiple conditions. Interventions should
      be evaluated for unintended negative effects on overall quality of care.

PMID- 16903879
TI  - An open, randomized comparison of artesunate plus mefloquine vs.
      dihydroartemisinin-piperaquine for the treatment of uncomplicated Plasmodium
      falciparum malaria in the Lao People's Democratic Republic (Laos).
AB  - OBJECTIVE: To determine the efficacy and safety of oral dihydroartemisinin
      piperaquine (DP, Artekin) in the treatment of uncomplicated Plasmodium falciparum
      malaria in southern Laos. METHODS: An open, randomized clinical trial of oral
      artesunate-mefloquine (AM) vs. DP in 220 patients with acute uncomplicated
      falciparum malaria in Savannakhet Province, Laos. RESULTS: The 42-day cure rates
      (95% CI), as determined by survival analysis and adjusted for reinfection, were
      excellent and similar for the two groups [99 (94-100)% and 100 (100-100)% for AM
      and DP, respectively]. The median (range) fever and parasite clearance times for
      the AM and DP groups were also similar [20 (4-63) h and 2 (1-4) days vs. 20 (7
      57) and 2 (1-4) days, logrank P = 0.4 and 0.17, respectively]. There were more
      patients with at least one potential side effect following treatment in the AM
      group when compared with the DP group [64/110 (58%) vs. 48/110 (44%),
      respectively, P = 0.031]. CONCLUSION: Dihydroartemisinin-piperaquine did not have
      superior efficacy to AM for the treatment of uncomplicated falciparum malaria in
      Laos but was associated with fewer adverse effects.

PMID- 16903881
TI  - The effect of altitude on parasite density case definitions for malaria in
      northeastern Tanzania.
AB  - OBJECTIVES: Malaria clinical trials need precise endpoints to measure efficacy.
      In endemic areas where asymptomatic parasitaemia is common, 'fever plus
      parasitaemia' may not differentiate between malaria cases and non-cases. Case
      definitions based on parasite cut-off densities may be more appropriate but may
      vary with age and transmission intensity. This study examines appropriate case
      definitions from parasitological surveys conducted over a broad range of
      transmission intensities, using altitude as a proxy for transmission intensity.
      METHODS: Cross-sectional data collected from 24 villages at different altitudes
      in an endemic area of northeastern Tanzania were used to calculate malaria
      attributable fractions using a modified Poisson regression method. We modelled
      fever as a function of parasite density and determined the optimum cut-off
      densities of parasites to cause fever using sensitivity and specificity analyses.
      RESULTS: The optimum cut-off density varied by altitude in children aged under 5
      years: a case definition of 4,000 parasites per mul at altitudes <600 m (high
      transmission intensity) was most appropriate, compared with 1,000 parasites per
      mul at altitudes >600 m (low transmission intensity). In children aged over 5
      years and adults, there was little variation by altitude and a case definition of
      any parasites plus fever was the most appropriate. CONCLUSIONS: Locally
      appropriate case definitions of malaria should be used for research purposes. In
      our setting, these varied independently with age and transmission intensity.

PMID- 16903882
TI  - The financial and clinical implications of adult malaria diagnosis using
      microscopy in Kenya.
AB  - OBJECTIVE: A recent observational study undertaken at 17 health facilities with
      microscopy in Kenya revealed that potential benefits of malaria microscopy are
      not realized because of irrational clinical practices and the low accuracy of
      routine microscopy. Using these data, we modelled financial and clinical
      implications of revised clinical practices and improved accuracy of malaria
      microscopy among adult outpatients under the artemether-lumefantrine (AL)
      treatment policy for uncomplicated malaria in Kenya. METHODS: The cost of AL,
      antibiotics and malaria microscopy and the expected number of malaria diagnosis
      errors were estimated per 1,000 adult outpatients presenting at a facility with
      microscopy under three scenarios: (1) current clinical practice and accuracy of
      microscopy (option A), (2) revised clinical practice with current accuracy of
      microscopy (option B) and (3) revised clinical practice with improved accuracy of
      microscopy (option C). Revised clinical practice was defined as performing a
      blood slide for all febrile adults and prescribing antimalarial treatment only
      for positive results. Improved accuracy of routine microscopy was defined as 90%
      sensitivity and specificity. In the sensitivity analysis, the implications of
      changes in the cost of drugs and malaria microscopy and changes in background
      malaria prevalence were examined for each option. RESULTS: The costs of AL,
      antibiotics and malaria microscopy decreased from 2,154 dollars under option A to
      1,254 dollars under option B and 892 dollars under option C. Of the cost savings
      from option C, 72% was from changes in clinical practice, while 28% was from
      improvements in the accuracy of microscopy. Compared with 638 malaria
      overdiagnosis errors per 1,000 adults under option A, 375 and 548 fewer
      overdiagnosis errors were estimated, respectively, under options B and C. At the
      same time, the number of missed malaria diagnoses remained generally low under
      all options. Sensitivity analysis showed that both options B and C are robust to
      a wide range of assumptions on the costs of drugs, costs of blood slides and
      malaria prevalence. CONCLUSIONS: Even with the imperfect microscopy conditions at
      Kenyan facilities, implementation of revised clinical practice (option B) would
      substantially reduce the costs and errors from malaria overdiagnosis. Additional
      interventions to improve the accuracy of microscopy (option C) can achieve
      further benefits; however, improved microscopy in the absence of revised clinical
      practice is unlikely to generate significant cost savings. Revision of guidelines
      to state explicitly age-specific indications for the use and interpretation of
      malaria microscopy is urgently needed. Further prospective studies are required
      to evaluate the effectiveness and costs of interventions to improve clinical
      practice and the accuracy of malaria microscopy.

PMID- 16903880
TI  - Insecticide-treated bednets for the prevention of Plasmodium falciparum malaria
      in Cambodia: a cluster-randomized trial.
AB  - OBJECTIVES: To validate and quantify the impact of insecticide-treated bednets
      (ITN) on malaria morbidity and mortality in Cambodia. METHODS: A paired, cluster
      randomized trial of ITN was conducted in Rattanakiri, North East Cambodia. Thirty
      four villages with a total population of 10,726 were randomized to receive
      deltamethrin-impregnated bednets or to control (no net provision). Cross
      sectional surveys measured Plasmodium falciparum prevalence at baseline and 10
      months after ITN distribution. Village malaria volunteers in control and
      intervention villages treated dipstick-positive P. falciparum cases with
      artesunate and mefloquine. The resulting passive surveillance data were used as
      an estimate of the incidence of clinical P. falciparum infections. RESULTS: There
      was a protective efficacy of 28% in P. falciparum incidence (adjusted rate ratio
      0.72, 95% CI 0.47-1.08) and 9% in P. falciparum prevalence (adjusted prevalence
      ratio 0.91, 95% CI 0.65-1.28) in ITN relative to control villages; however,
      neither of these estimates reached statistical significance. Individual-level
      analysis indicated a greater reduction in P. falciparum prevalence among under 5
      year-olds (adjusted OR = 0.63, 95% CI 0.26-1.53) compared to older individuals
      (interaction P = 0.042). The protective efficacy of 35% (95% CI -28, 67%) with
      respect to clinical P. falciparum incidence in under 5-year-olds was more
      pronounced than the corresponding estimates for prevalence but was again not
      significant. CONCLUSIONS: Lack of statistical significance in the results is
      likely to be due to a lack of power. The analysis provides further evidence for
      ITN effectiveness in South East Asia, particularly among individuals under 5
      years of age.

PMID- 16903883
TI  - Low larval vector survival explains unstable malaria in the western Kenya
      highlands.
AB  - Several highland areas in eastern Africa have recently suffered from serious
      malaria epidemics. Some models predict that, in the short term, these areas will
      experience more epidemics as a result of global warming. However, the various
      processes underlying these changes are poorly understood. We therefore
      investigated malaria prevalence, malaria vector densities and malaria vector
      survival in a highland area in western Kenya, ranging from approximately 1,550
      1,650 m altitude. Although only five adult malaria vectors were collected during
      180 light traps and 180 resting collections over a 23-month study period, malaria
      was prevalent among school children (average parasite prevalence: 10%). During an
      extensive survey of potential larval habitats, we identified only seven habitats
      containing Anopheles gambiae Giles s.l. larvae. Their limited number and low
      larval densities suggested that their contribution to the adult vector population
      was small. Experiments on adult and larval survival showed that at this altitude,
      adult mosquitoes survived inside local houses, but that larval development was
      severely retarded: only 2 of 500 A. gambiae s.l. larvae developed to the pupal
      stage, whereas all other larvae died prior to pupation. At present, high vector
      densities are unlikely because of unfavourable abiotic conditions in the area.
      However, temporary favourable conditions, such as during El Nino years, may
      increase larval vector survival and may lead to malaria epidemics.

PMID- 16903884
TI  - Gametocytocidal activity in antimalarial drugs speeds the spread of drug
      resistance.
AB  - OBJECTIVE: Antimalarial drugs kill the asexual parasites responsible for causing
      disease and some, notably chloroquine and the artemisinins, also kill the sexual
      transmission stages known as gametocytes. It is invariably argued by
      malariologists that gametocytocidal activity is beneficial because it reduces the
      rate at which resistance evolves by 'reducing the transmission of resistant
      parasites'. This seems dubious from a population genetics perspective, where
      intuition would lead to the opposite conclusion. The objective was to reconcile
      these differing views. METHODS: The effect of gametocytocidal drug activity was
      quantified mathematically and calibrated using field data. RESULTS: It appears to
      be a robust result that gametocytocidal activity actually promotes the spread of
      resistance through a population; the underlying reason is that gametocytocidal
      activity reduces transmission of drug-sensitive forms to a greater extent than
      the drug resistant, thereby increasing the spread of the latter. The increased
      rate of spread of resistance is quantified and appears to be small providing drug
      coverage is moderate or low. CONCLUSIONS: Citing reduced spread of resistance as
      a justification for deploying gametocytocidal antimalarials is unjustified; the
      deliberate use of a gametocytocidal antimalarial at high coverage to reduce
      transmission may ultimately be counterproductive through its rapid promotion of
      drug resistance.

PMID- 16903885
TI  - Rising under-5 mortality in Africa: who bears the brunt?
AB  - OBJECTIVES: To identify the socioeconomic and geographical groups in which the
      recent under-5 mortality increase observed in several African countries was most
      pronounced, and to explore the contribution of a number of proximate determinants
      of under-5 mortality. METHODS: Time trends in under-5 mortality were assessed
      with Cox Proportional Hazards regression analysis, using Demographic and Health
      Surveys data for Burkina Faso, Cameroon, Cote d'lvoire, Kenya and Zimbabwe for
      the late 1980s - 1990s. We tested for differences in time trends between
      socioeconomic and rural/urban subgroups, and described the inequalities in time
      trends in living conditions, malnutrition and health care use. RESULTS: Under-5
      mortality increased substantially (ranging from 25% to 71% in 10 years) within
      the five countries. In Kenya, the increase was the largest among children born to
      less educated mothers (test for difference between educational groups: P = 0.074)
      and in rural areas (P = 0.090). In Cameroon, the increase was the largest among
      the higher educated (P = 0.013), and in Zimbabwe among the higher educated (P =
      0.098) and in urban areas (P = 0.093). For Burkina Faso and Cote d'Ivoire, we did
      not observe statistically significant differences between educational and
      rural/urban subgroups. The decline in skilled delivery attendance in Zimbabwe and
      Kenya was similar among the less and higher educated. The decline in immunization
      coverage during the mid-1990s in Zimbabwe was the largest in the group with the
      highest mortality increase, but in Kenya it was as large among the less and
      higher educated. Whereas in Kenya the increase in malnutrition was the largest in
      the group with the highest mortality increase, this was not the case in Zimbabwe.
      CONCLUSIONS: The recent increase in under-5 mortality in some African countries
      was highly concentrated in specific population subgroups. Exactly which groups
      were most affected was highly variable. It cannot be assumed that lower
      socioeconomic groups are always most vulnerable. Strategies to halt the under-5
      mortality increase should be based on disaggregate information for individual
      countries.

PMID- 16903886
TI  - Epidemiological trends for human plague in Madagascar during the second half of
      the 20th century: a survey of 20,900 notified cases.
AB  - OBJECTIVES: To describe the principal characteristics and epidemiological trends
      for human plague in modern times based on the largest reported series of cases
      from the highly active Malagasy focus. METHODS: We used a file of 20,900 notified
      cases of suspected plague, 4,473 of which were confirmed or probable, to carry
      out a statistical analysis of incidence and mortality rates and associated
      factors for 5-year periods from 1957 to 2001. RESULTS: Our analysis of trends
      showed (1) an increase in the incidence rate and the number of districts
      affected, (2) an increase in the proportion of bubonic forms (64.8-96.8%) at the
      expense of the pneumonic forms (35.2-3.2%) more frequent in elderly subjects and
      (3) a decrease in case fatality rate (CFR, 55.7-20.9%) associated with five
      factors: clinical form, season, province, urban/rural and period considered. The
      median age of patients was 14 years and more men than women were affected.
      CONCLUSIONS: Since the end of the 1980s, the incidence of plague in Madagascar
      has increased in both rural and urban areas, because of multiple socioeconomic
      and environmental factors. However, the plague mortality rate has tended to
      decrease, together with the frequency of pneumonic forms, because of the
      strengthening of control measures. Making dipstick tests for the rapid diagnosis
      of human cases and epizootics in rats available for health structures should make
      it possible to raise the alarm and to react rapidly, thereby further decreasing
      morbidity and CFR.

PMID- 16903887
TI  - Classifying dengue: a review of the difficulties in using the WHO case
      classification for dengue haemorrhagic fever.
AB  - BACKGROUND: The current World Health Organisation (WHO) classification of dengue
      includes two distinct entities: dengue fever (DF) and dengue haemorrhagic fever
      (DHF)/dengue shock syndrome; it is largely based on pediatric cases in Southeast
      Asia. Dengue has extended to different tropical areas and older age groups.
      Variations from the original description of dengue manifestations are being
      reported. OBJECTIVES: To analyse the experience of clinicians in using the dengue
      case classification and identify challenges in applying the criteria in routine
      clinical practice. METHOD: Systematic literature review of post-1975 English
      language publications on dengue classification. RESULTS: Thirty-seven papers were
      reviewed. Several studies had strictly applied all four WHO criteria in DHF
      cases; however, most clinicians reported difficulties in meeting all four
      criteria and used a modified classification. The positive tourniquet test
      representing the minimum requirement of a haemorrhagic manifestation did not
      distinguish between DHF and DF. In cases of DHF thrombocytopenia was observed in
      8.6-96%, plasma leakage in 6-95% and haemorrhagic manifestations in 22-93%. The
      low sensitivity of classifying DHF could be due to failure to repeat the tests or
      physical examinations at the appropriate time, early intravenous fluid therapy,
      and lack of adequate resources in an epidemic situation and perhaps a
      considerable overlap of clinical manifestations in the different dengue entities.
      CONCLUSION: A prospective multi-centre study across dengue endemic regions, age
      groups and the health care system is required which describes the clinical
      presentation of dengue including simple laboratory parameters in order to review
      and if necessary modify the current dengue classification.

PMID- 16903888
TI  - Operational feasibility of lot quality assurance sampling (LQAS) as a tool in
      routine process monitoring of filariasis control programmes.
AB  - Lot quality assurance sampling (LQAS) with two-stage sampling plan was applied
      for rapid monitoring of coverage after every round of mass drug administration
      (MDA). A Primary Health Centre (PHC) consisting of 29 villages in Thiruvannamalai
      district, Tamil Nadu was selected as the study area. Two threshold levels of
      coverage were used: threshold A (maximum: 60%; minimum: 40%) and threshold B
      (maximum: 80%; minimum: 60%). Based on these thresholds, one sampling plan each
      for A and B was derived with the necessary sample size and the number of
      allowable defectives (i.e. defectives mean those who have not received the drug).
      Using data generated through simple random sampling (SRSI) of 1,750 individuals
      in the study area, LQAS was validated with the above two sampling plans for its
      diagnostic and field applicability. Simultaneously, a household survey (SRSH) was
      conducted for validation and cost-effectiveness analysis. Based on SRSH survey,
      the estimated coverage was 93.5% (CI: 91.7-95.3%). LQAS with threshold A revealed
      that by sampling a maximum of 14 individuals and by allowing four defectives, the
      coverage was >or=60% in >90% of villages at the first stage. Similarly, with
      threshold B by sampling a maximum of nine individuals and by allowing four
      defectives, the coverage was >or=80% in >90% of villages at the first stage.
      These analyses suggest that the sampling plan (14,4,52,25) of threshold A may be
      adopted in MDA to assess if a minimum coverage of 60% has been achieved. However,
      to achieve the goal of elimination, the sampling plan (9, 4, 42, 29) of threshold
      B can identify villages in which the coverage is <80% so that remedial measures
      can be taken. Cost-effectiveness analysis showed that both options of LQAS are
      more cost-effective than SRSH to detect a village with a given level of coverage.
      The cost per village was US dollars 76.18 under SRSH. The cost of LQAS was US
      dollars 65.81 and 55.63 per village for thresholds A and B respectively. The
      total financial cost of classifying a village correctly with the given threshold
      level of LQAS could be reduced by 14% and 26% of the cost of conventional SRSH
      method.

PMID- 16903889
TI  - Who needs 'pukka anthropologists'? A study of the perceptions of the use of
      anthropology in tropical public health research.
AB  - Over the past 50 years, there have been considerable changes both in how medical
      anthropologists view their relationship to tropical public health and in how
      tropical public health professionals view the role of anthropologists. In
      particular, in recent decades critical currents have emerged from an anthropology
      of medicine, calling for an examination of biomedicine and its conceptualisation
      of public health. There are parallel debates in public health about a narrow
      disease-focused or broader socio-cultural approach to improving population
      health. Based on a review of the literature and a qualitative study of the views
      of public health professionals and anthropologists working in tropical public
      health, the data presented in this paper suggest that public health professionals
      remain unaware of many of the contributions anthropology could make to tropical
      public health theory and practice. However, the objectives of a critical social
      science are not dissimilar to those of the broader concept of public health. We
      suggest that there are grounds for optimism. For those of us concerned not just
      with disease but also with inequities in health, the challenge is to work towards
      a critical tropical public health which draws as much from social science as from
      biomedicine, in theory and practice.

PMID- 16903890
TI  - Geographic and temporal genetic patterns of Aedes aegypti populations in Rio de
      Janeiro, Brazil.
AB  - Rio de Janeiro is considered as the most important entry point for dengue viruses
      in Brazil. Using isoenzyme markers, we investigated the genetic structure of the
      mosquito vector Aedes aegypti sampled at three-month intervals in 14 districts in
      Rio de Janeiro from December 2002 to December 2003. We detected high levels of
      genetic differentiation (i.e. high F(ST) values and significant P values), which
      tended to persist throughout the year. The species does not take advantage of
      routes and railways to disperse. Genetic structuring was higher in the rainy
      season, suggesting low dispersion of Ae. aegypti at this time of year when all
      dengue epidemics have been reported in the city.

PMID- 16903891
TI  - Large scale evaluation of WHO's ultrasonographic staging system of schistosomal
      periportal fibrosis in Ethiopia.
AB  - OBJECTIVES: To evaluate the recent WHO's ultrasonographic diagnostic staging
      system of schistosomal periportal thickening/fibrosis and to assess intra/inter
      observer variation associated with its use. METHODS: Local standard of portal
      branch wall thickness (PBWT) for height was established using 150 healthy
      subjects. Intra and inter-observer variation in image pattern identification and
      PBWT measurements were assessed in 94 and 35 subjects, respectively, with
      differing stages of periportal thickening fibrosis. WHO's diagnostic criteria
      were evaluated in 2,451 community members (1,277 males, 1,174 females; mean age
      18.8 years) with an overall Schistosoma mansoni prevalence estimate of 65.9%.
      RESULTS: There were no significant inter/intra-observer variations in image
      pattern identification and PBWT measurements. Based on Ethiopian PBWT-for-height
      standard, 128/2,451 (5.2%) had insipient, 46/2,451 (1.9%) had possible/probable
      and 112/2451 (4.6%) had definite/advanced periportal thickening/fibrosis.
      Comparable figures were obtained using the Senegalese PBWT-for-height standard
      and there was good agreement between Ethiopian and Senegalese healthy control
      based diagnostic criteria in classifying the 286 subjects into stages of
      periportal thickening/fibrosis (kappa = 0.87, P < 0.001). CONCLUSIONS: With
      further improvement, the WHO's ultrasonographic diagnostic criteria can be used
      in health institutions and community surveys. Image pattern based assessment is
      simple and more reproducible than PBWT based assessment of periportal
      thickening/fibrosis. The latter is, however, more useful in clarifying the status
      of an individual with doubtful image pattern, and in monitoring post-treatment
      outcome of periportal thickening/fibrosis. Considering the comparability of PBWT
      for-height standards, setting one international standard of PBWT-for-height is
      more practical than developing local standards for each endemic area.

PMID- 16903892
TI  - Relationship between haemoglobin and haematocrit in the definition of anaemia.
AB  - INTRODUCTION: Anaemia is the most frequent haematological disorder in childhood.
      The notion that defines naemia does not change throughout life, although
      parameters used for its evaluation show significant variations during childhood.
      Haematocrit (Hct) (%) is usually defined as three times the value of haemoglobin
      (Hgb) (g/dl), while the clinical definition of anaemia is related to either an
      abnormal Hct or Hgb value. OBJECTIVE: To evaluate the agreement between Hgb and
      Hct values in the definition of anaemia, the relationship between these two
      parameters and their age-dependence. METHODS: The Hct and Hgb paired values from
      children aged 2-18 months from Ifakara (Tanzania) and children aged 1-4 years
      from Manhica (Mozambique) were analysed. Haematological determinations of the
      Manhica samples were done using a KX-21N cell counter (Kobe, Japan) and Ifakara
      samples were analysed in a semiautomatic cell counter (Sysmex F800 microcell
      counter, TOA Medical Electronics, Kobe, Japan). The kappa-statistic was used to
      calculate the agreement between anaemia definitions in each group. Crude and
      multivariate relationship between Hct and Hgb levels were analysed by linear
      regression model estimation. The age-dependence of the crude ratio (Hct/Hgb) was
      analysed using linear regression models and fractional polynomials. RESULTS: The
      prevalences of mild and moderate anaemia as defined by Hgb levels in the Manhica
      group were 61% and 6%, respectively, and 41% and 2% by Hct. In the Ifakara group
      these were 74% and 10%, respectively, by Hgb and 42% and 3% by Hct, respectively.
      Agreement between mild and moderate anaemia definitions made up from Hgb or from
      Hct levels were from fair to moderate. Hct levels decreased with age for high Hgb
      levels, whereas they increased for low Hgb levels. The classification of cases is
      improved when higher age-related cut-off values for Hct are used. The crude
      relationship between Hct and Hgb levels was significantly different from 3, and
      this was modified by age. The evaluation of the age-dependence ratio (Hct/Hgb)
      showed a non-linear relationship with an asymptotic trend to 3. CONCLUSIONS:
      Measurement of haematocrit count is easy and can be performed in most rural
      health care centres. However, the corresponding Hgb levels cannot be derived with
      an acceptable accuracy using the value 3 as a conversion factor. Furthermore, the
      commonly assumed 'equivalent' cut-off points for anaemia definitions need to be
      re-evaluated.

PMID- 16903893
TI  - Reviewing institutions of rural health centres: the Performance Initiative in
      Butare, Rwanda.
AB  - In many low-income countries, performance of pyramidal health systems with a
      public purpose is not meeting the expectations and needs of the populations they
      serve. A question that has not been studied and tested sufficiently is, 'What is
      the right package of institutional mechanisms required for organisations and
      individuals working in these health systems?' This paper presents the experience
      of the Performance Initiative, an innovative contractual approach that has
      reshaped the incentive structure in place in two rural districts of Rwanda. It
      describes the general background, the initial analysis, the institutional
      arrangement and the results after 3 years of operations. At this stage of the
      experience, it shows that 'output-based payment + greater autonomy' is a feasible
      and effective strategy for improving the performance of public health centres. As
      part of a more global package of strategies, contracting-in approaches could be
      an interesting option for governments, donors and non-governmental organisations
      in their effort to achieve some of the Millennium Development Goals.

PMID- 16903894
TI  - Mapping the environmental coverage of the INDEPTH demographic surveillance system
      network in rural Africa.
AB  - OBJECTIVES: The INDEPTH DSS network was founded in 1998 to provide an
      international network of field sites for continuous demographic evaluation of
      populations and their health. Results from the network have been used to derive
      estimates of mortality, morbidity and health equity. Spatial extrapolation and
      logical summaries of these findings are dependent on the network covering a
      representative sample of the environments in a region and their
      interrelationships being known. Here, we investigate how comprehensive is the
      coverage of the network of rural DSS sites in Africa in terms of the range of
      ecological zones found across the continent. METHODS: We used satellite imagery
      to define an environmental signature for each INDEPTH DSS site, and then
      calculate Euclidean distances from these signatures to the environmental
      signatures of every image pixel across Africa. These distances were then mapped
      and a gridded population surface used to mask uninhabited areas to illustrate the
      extent of the environmental coverage of the INDEPTH network. Environmental
      similarities between DSS sites were also calculated, hierarchically clustered and
      visualized as a dendrogram to examine between site relationships. Finally, an
      ecozonation of Africa was used to analyse the per-ecozone environmental
      similarity of the INDEPTH DSS network. RESULTS AND CONCLUSIONS: The current
      INDEPTH DSS network in Africa spans all the major environmental zones, but within
      these zones the environmental coverage of the network varies. These variations
      were mapped by ecozone. These maps provide valuable information in determining
      the confidence with which relationships derived from rural INDEPTH DSS sites can
      be extended to other areas. The results also indicate suites of sites that form
      environmentally cohesive groups and from which data can be logically summarized.
      Finally, the results highlight areas where the location of new INDEPTH DSS sites
      would increase significantly the environmental coverage of the network.

PMID- 16903895
TI  - Thresholds for health insurance in Rwanda: who should pay how much?
AB  - Community-based health insurance schemes were introduced in Rwanda in 1999 and
      now cover 27% of the population. Due to widespread poverty, it remains unclear to
      what degree poorer population strata can be anticipated to pay into the system.
      This study investigates the extent to which the Rwandan population can
      financially contribute to obtain health insurance. More specifically, researchers
      explored the relationship between resource mobilization for the health system and
      the ability to provide community-based health insurance across socio-economic
      strata. Data from six household surveys are analysed revealing a consistent
      pattern: the goals of maximizing health revenue and maximizing participation in
      community-based health insurance are mutually exclusive. However, the upper three
      quartiles of the Rwandan population are able to contribute 1 US dollar per capita
      per year. In order to extend coverage to the poorest quartile, a corresponding
      subsidy for the coming years has to be considered.

PMID- 16903896
TI  - Sudden cardiac death (SCD) associated with sports in young individuals.

PMID- 16903897
TI  - Secular trends in cardiorespiratory fitness and body mass index in Danish
      children: The European Youth Heart Study.
AB  - AIM: To examine the secular trends in cardiorespiratory fitness (CF) and body
      fatness in Danish children. Trends were analyzed overall and across socioeconomic
      status (SES). METHODS: Two cross-sectional studies conducted on 589 and 458 third
      grade Danish children in 1997-1998 and 2003-2004, respectively. CF was determined
      by a maximal cycle-ergometer test. The lowest sex-specific quartile of CF in the
      study from 1997 to 1998 was used as a cut-point for low CF. Body mass index (BMI)
      cut-points were used to describe overweight, and SES was divided into two groups
      according to parents' occupation. RESULTS: This study showed a secular decline in
      CF in girls overall. Increased CF, BMI, and prevalence of overweight were
      observed in boys with high SES, in boys with low SES, and in girls with low SES,
      respectively. However, after additional Bonferroni's correction, none of the
      statistical analyses performed across socioeconomic gradients reached significant
      P-values. CONCLUSION: CF declined in girls overall. Although not statistically
      significant after additional Bonferroni's correction, results in general showed
      less favorable trends in low SES children. Thus, trying to describe secular
      trends in CF and body fatness overall without any regard to SES might disguise
      social-caused differences. However, further studies are needed in order to verify
      this hypothesis.

PMID- 16903898
TI  - Acute mortality during long-distance ski races (Vasaloppet).
AB  - OBJECTIVE: We studied mortality during long-distance ski races in Sweden. DESIGN:
      The cohort comprised all subjects who participated in ski races during the
      Vasaloppet week from 1970 through 2005. All deaths during the races were
      identified and compared with the corresponding expected numbers based on national
      death rates. RESULTS: In total, 698 102 starters generated altogether 581 person
      years of skiing. Overall, 13 deaths occurred compared with 1.68 expected during
      the skiing time, yielding a standardized mortality ratio (SMR) of 7.7 [95%
      confidence interval (CI) 4.1-13.2]. Twelve of the deaths were caused by
      cardiovascular disease (SMR=22.1, 95% CI 11.4-38.6). Interviews of relatives
      revealed that two to four victims had medical conditions of the sort that they
      probably would have been recommended to avoid participation for medical reasons
      had they consulted a physician. CONCLUSION: Our study showed a clearly increased
      risk of acute mortality during long-distance skiing. However, as physically
      active people spend only a minority of their time in races, in that population
      the short-term excess mortality during these periods is by far outweighed by the
      long-term protective effects of exercise on mortality.

PMID- 16903899
TI  - Leisure-time physical activity of 13-year-old adolescents.
AB  - The leisure-time physical activity of 13-year-old Finnish adolescents was
      assessed in the prospective STRIP study. A self-administered questionnaire
      (N=565) was used. The leisure-time physical activity index (PAI; MET h/week) was
      calculated on the basis of reported exercise intensity, duration and frequency
      (N=558; 53% boys). The participants were divided into Sedentary, Moderately
      Active and Active groups by PAI tertiles. A subpopulation (N=197) also used a
      heart rate monitor (3 days, >/=8 h/day) to assess the time spent on different
      activity intensities. The median male PAI was 31.3 (inter-quartile range (IQR)
      44.2) MET h/week and female 19.5 (IQR 26.3) MET h/week (P=0.0002). The cutoff
      points of the PAI tertiles were similar for the Active girls (31.3 MET h/week)
      and boys (32.6 MET h/week), but for the Sedentary boys it was 19.5 MET h/week and
      only 5.0 MET h/week for the Sedentary girls. High self-reported leisure-time
      physical activity associated poorly with time spent on moderate or vigorous
      exercise measured by heart rate monitoring. Active mothers had more often Active
      daughters or sons. In conclusion, the amount of leisure-time physical activity of
      one-third of 13-year-old girls is extremely low. Sedentary adolescents,
      especially girls, should therefore be put into focus for active efforts to
      increase their leisure-time physical activity. Parental models may be important.

PMID- 16903900
TI  - Effects on leg muscular performance from whole-body vibration exercise: a
      systematic review.
AB  - The purpose of this study was to investigate the effects on leg muscular
      performance from whole-body vibration exercise. Literature search was performed
      on the databases Pubmed, Cinahl, ISI web of science (Sci-expanded, SSCI) and
      Embase (Rehab & Physical Med). Rating of 19 relevant studies was performed (14 on
      long-term exercise and five on short-term exercise) using a score system for the
      methodological quality. Several randomized-controlled trial studies of high to
      moderate quality show similar improvements from long-term regimen on muscular
      performance in the legs after a period of whole-body vibration exercise. As there
      were few studies on short-term exercise and as they had no control groups, the
      same convincing improvements regarding muscular performance were not achieved.
      Preliminarily, there is strong to moderate evidence that long-term whole-body
      vibration exercise can have positive effects on the leg muscular performance
      among untrained people and elderly women. There is no clear evidence for effects
      on muscular performance after short-term vibration stimuli.

PMID- 16903901
TI  - Onset of promiscuous gene expression in murine fetal thymus organ culture.
AB  - T-cell differentiation and induction of tolerance to self-antigens occurs mainly
      in the thymus. Thymic stromal cells, specifically medullary thymic epithelial
      cells, express a diverse set of genes encoding parenchymal organ-specific
      proteins. This phenomenon has been termed promiscuous gene expression (PGE) and
      has been implicated in preventing organ-specific autoimmunity by inducing T-cell
      tolerance to self antigens. Early thymopoiesis and the critical factors involved
      in T-cell differentiation can be reproduced in vitro by murine fetal thymus organ
      culture (FTOC), which mimics the natural thymic microenvironment. To evaluate the
      occurrence of PGE in FTOC, gene expression profiling during in vitro thymic
      development in BALB/c mice was performed using a set of nylon cDNA microarrays
      containing 9216 sequences. The statistical analysis of the microarray data (sam
      program) revealed the temporal repression and induction of 57 parenchymal and
      seven lymphoid organ-specific genes. Most of the genes analysed are repressed
      during early thymic development (15-17 days post-coitum). The expression of the
      autoimmune regulator (AIRE) gene at 16 days post-coitum marks the onset of PGE.
      This precedes the induction of parenchymal organ genes during the late
      developmental phase at 20 days post-coitum. The mechanism of T-cell tolerance
      induction begins during fetal development and continues into adulthood. Our
      findings are significant because they show a fine demarcation of PGE onset, which
      plays a central role in induction of T-cell tolerance.

PMID- 16903903
TI  - Foxp3+ CD25+ CD4+ natural regulatory T cells in dominant self-tolerance and
      autoimmune disease.
AB  - Naturally arising CD25+ CD4+ regulatory T (Treg) cells, most of which are
      produced by the normal thymus as a functionally mature T-cell subpopulation, play
      key roles in the maintenance of immunologic self-tolerance and negative control
      of a variety of physiological and pathological immune responses. Natural Tregs
      specifically express Foxp3, a transcription factor that plays a critical role in
      their development and function. Complete depletion of Foxp3-expressing natural
      Tregs, whether they are CD25+ or CD25-, activates even weak or rare self-reactive
      T-cell clones, inducing severe and widespread autoimmune/inflammatory diseases.
      Natural Tregs are highly dependent on exogenously provided interleukin (IL)-2 for
      their survival in the periphery. In addition to Foxp3 and IL-2/IL-2 receptor,
      deficiency or functional alteration of other molecules, expressed by T cells or
      non-T cells, may affect the development/function of Tregs or self-reactive T
      cells, or both, and consequently tip the peripheral balance between the two
      populations toward autoimmunity. Elucidation of the molecular and cellular basis
      of this Treg-mediated active maintenance of self-tolerance will facilitate both
      our understanding of the pathogenetic mechanism of autoimmune disease and the
      development of novel methods of autoimmune disease prevention and treatment via
      enhancing and re-establishing Treg-mediated dominant control over self-reactive T
      cells.

PMID- 16903904
TI  - Interleukin-10-secreting type 1 regulatory T cells in rodents and humans.
AB  - Interleukin-10 (IL-10)-secreting T regulatory type 1 (Tr1) cells are defined by
      their specific cytokine production profile, which includes the secretion of high
      levels of IL-10 and transforming growth factor-beta(TGF-beta), and by their
      ability to suppress antigen-specific effector T-cell responses via a cytokine
      dependent mechanism. In contrast to the naturally occurring CD4+ CD25+ T
      regulatory cells (Tregs) that emerge directly from the thymus, Tr1 cells are
      induced by antigen stimulation via an IL-10-dependent process in vitro and in
      vivo. Specialized IL-10-producing dendritic cells, such as those in an immature
      state or those modulated by tolerogenic stimuli, play a key role in this process.
      We propose to use the term Tr1 cells for all IL-10-producing T-cell populations
      that are induced by IL-10 and have regulatory activity. The full biological
      characterization of Tr1 cells has been hampered by the difficulty in generating
      these cells in vitro and by the lack of specific marker molecules. However, it is
      clear that Tr1 cells play a key role in regulating adaptive immune responses both
      in mice and in humans. Further work to delineate the specific molecular signature
      of Tr1 cells, to determine their relationship with CD4+ CD25+ Tregs, and to
      elucidate their respective role in maintaining peripheral tolerance is crucial to
      advance our knowledge on this Treg subset. Furthermore, results from clinical
      protocols using Tr1 cells to modulate immune responses in vivo in autoimmunity,
      transplantation, and chronic inflammatory diseases will undoubtedly prove the
      biological relevance of these cells in immunotolerance.

PMID- 16903905
TI  - The immunoregulatory effects of Qa-1.
AB  - The immune system is not only well equipped to control infections but also
      tightly controlled to prevent autoimmune disease. Despite the negative selection
      of T-cell clones in the thymus, mature T cells capable of recognizing self
      antigens are present in every individual. Several types of specialized regulatory
      cells maintain homeostasis and prevent expansion of autoreactive T cells. In this
      issue of Immunological Reviews, the role of CD4+ regulatory T cells is
      extensively discussed. Suppression of T-cell responses by CD8+ T cells has
      received less attention. Here, we review research on Qa-1-restricted CD8+
      regulatory T cells. We focus on the role of this class Ib major
      histocompatibility complex (MHC) molecule in both CD8+ regulatory T-cell activity
      and protection of activated T cells.

PMID- 16903906
TI  - The lifestyle of naturally occurring CD4+ CD25+ Foxp3+ regulatory T cells.
AB  - Numerous studies over the past 10 years have demonstrated the importance of
      naturally occurring CD4+ CD25+ Foxp3+ regulatory T cells (nTregs) in immune
      regulation. We analyzed the mechanism of action of nTregs in a well-characterized
      model of autoimmune gastritis and demonstrated that nTregs act at an early stage
      of disease progression to inhibit the differentiation of naive T cells to
      pathogenic T-helper 1 effectors. The effects of nTregs in this model are not
      antigen-specific but are mediated by activation of the nTregs by ubiquitous self
      peptide major histocompatibility complex class II complexes together with
      cytokines released by activated effector cells. Studies in vitro confirmed that
      some nTregs exist in an activated state in vivo and can be activated to exert non
      specific suppressor effector function by stimulation with interleukin-2 in the
      absence of engagement of their T-cell receptor. Natural Tregs can differentiate
      in vitro to exhibit potent granzyme B-dependent, partially perforin-independent
      cytotoxic cells that are capable of specifically killing antigen-presenting B
      cells. Natural Treg-mediated killing of antigen-presenting cells may represent
      one pathway by which they can induce long-lasting suppression of autoimmune
      disease.

PMID- 16903907
TI  - Role of TCR specificity in CD4+ CD25+ regulatory T-cell selection.
AB  - CD4+ CD25+ regulatory T cells play a crucial role in preventing autoimmune
      disease and can also modulate immune responses in settings such as
      transplantation and infection. We have developed a transgenic mouse system in
      which the role that T-cell receptor (TCR) specificity for self-peptides plays in
      the formation of CD4+ CD25+ regulatory T cells can be examined. We have shown
      that interactions with a single self-peptide can induce thymocytes bearing an
      autoreactive TCR to undergo selection to become CD4+ CD25+ regulatory T cells and
      that thymocytes bearing TCRs with low affinity for the selecting peptide do not
      appear to undergo selection into this pathway. In addition, thymocytes with
      identical specificity for the selecting self-peptide can undergo overt deletion
      versus abundant selection to become CD4+ CD25+ regulatory T cells in response to
      variations in expression of the selecting peptide in different lineages of
      transgenic mice. Finally, we have shown that CD4+ CD25+ T cells proliferate in
      response to their selecting self-peptide in the periphery, but these cells do not
      proliferate in response to lymphopenia in the absence of the selecting self
      peptide. These studies are determining how the specificity of the TCR for self
      peptides directs the thymic selection and peripheral expansion of CD4+ CD25+
      regulatory T cells.

PMID- 16903908
TI  - The role of the transcription factor Foxp3 in the development of regulatory T
      cells.
AB  - Early studies of mice subjected to neonatal thymectomy and analyses of adoptive T
      cell transfer into lymphopenic hosts led to the identification of a specialized
      subset of regulatory CD4+ T cells capable of suppressing various manifestations
      of autoimmunity. Recently, a combination of genetic, molecular, and traditional
      cellular approaches provided novel powerful means to investigate the biology of
      these cells. Here, we review earlier and current work from our laboratory,
      establishing a dedicated function for the transcription factor Foxp3 in the
      process of regulatory T-cell lineage commitment and a role for TCR- and cytokine
      mediated signals in regulation of Foxp3 expression.

PMID- 16903909
TI  - FOXP3 ensembles in T-cell regulation.
AB  - Our recent studies have identified dynamic protein ensembles containing forkhead
      box protein 3 (FOXP3) that provide insight into the molecular complexity of
      suppressor T-cell activities, and it is our goal to determine how these ensembles
      regulate FOXP3's transcriptional activity in vivo. In this review, we summarize
      our current understanding of how FOXP3 expression is induced and how FOXP3
      functions in vivo as a transcriptional regulator by assembling a multisubunit
      complex involved in histone modification as well as chromatin remodeling.

PMID- 16903910
TI  - The roles for cytokines in the generation and maintenance of regulatory T cells.
AB  - As an essential mechanism for self-tolerance, immune suppression has attracted
      much attention since the discovery of suppressor T cells, now called regulatory T
      cells (Tregs), in the 1990s. Different types of Tregs have been described based
      on distinct expression patterns of surface markers and cytokines. Cytokines are
      not only essential for function but also important for the generation of Tregs.
      Interleukin-2 (IL-2), transforming growth factor-beta, IL-10, and other
      immunoregulatory molecules have been shown to control the generation of Tregs.
      The presence of other types of cells, in particular antigen-presenting cells
      (APCs), is critical for the generation of Tregs. Cytokines can serve as either
      initiators or intermediates for the interactions between APCs and Tregs. This
      review discusses our current knowledge of how cytokines regulate the generation
      and maintenance of Tregs.

PMID- 16903911
TI  - The role of CD28 and cytotoxic T-lymphocyte antigen-4 (CTLA-4) in regulatory T
      cell biology.
AB  - The profound influence of CD28 and cytotoxic T-lymphocyte antigen-4 (CTLA-4) on T
      cell immunity has been known for over a decade, yet the precise roles played by
      these molecules still continue to emerge. Initially viewed as molecules that
      provide cell-intrinsic costimulatory and inhibitory signals, recent evidence
      suggests that both CD28 and CTLA-4 are also important in the homeostasis and
      function of a population of suppressive cells, termed regulatory T cells (Tregs).
      Here we review the main features of the CD28 and CTLA-4 system and examine how
      these impact upon Treg biology.

PMID- 16903912
TI  - Regulatory T cells in the periphery.
AB  - Recognition of a systemic antigen by CD4+ T cells in a lymphopenic host leads to
      the sequential generation of pathogenic effector cells and protective CD25+
      forkhead box protein (Foxp3+) regulatory T cells (Tregs) in the periphery. Such
      an experimental model is potentially valuable for defining the stimuli that
      determine the balance of effector and regulatory T cells. Our studies have shown
      that interleukin-2 (IL-2) enhances the development of effector cells and is
      essential for the peripheral generation of regulatory cells. Other models of
      peripheral Treg generation suggest that the concentration of antigen, the nature
      of the antigen-presenting cells, and cytokines such as transforming growth factor
      beta and IL-10 may all influence the peripheral generation of Tregs.

PMID- 16903913
TI  - Making regulatory T cells with defined antigen specificity: role in autoimmunity
      and cancer.
AB  - There is increasing evidence that agonist ligand presentation either
      intrathymically or extrathymically plays a crucial if not essential role in the
      generation of regulatory T cells (Tregs). Thus, it is possible to induce Tregs of
      any desired specificity in vivo. The same goal can be achieved in vitro by
      expanding antigen-specific CD4+ T cells and retrovirally transducing them. In
      contrast, in vitro expansion of Tregs is limited to antigens that have resulted
      in Treg generation in vivo. Antigen-specific Tregs can be used in cellular
      therapy with the goal to prevent autoimmune disease or even to interfere with
      established autoimmunity. The latter requires that the Tregs can suppress
      effector cells that have already caused harm, which is possible because of the
      antigen-dependent homing properties of Tregs, i.e. these cells can accumulate in
      antigen-draining lymph nodes and exit into inflamed tissue. Generally, the in
      vivo interference is dependent on cytokines such as transforming growth factor
      beta and interleukin-10 that were dispensable in in vivo analysis of
      immunosuppression. The precise mechanisms of suppression remain enigmatic,
      however, but may be further elucidated by the molecular analysis of suppressed
      versus non-suppressed T cells.

PMID- 16903914
TI  - The role of physiological self-antigen in the acquisition and maintenance of
      regulatory T-cell function.
AB  - The CD4+ CD25+ regulatory T cells (Tregs) are efficient regulators of
      autoimmunity, but the mechanism remains elusive. We summarize recent data for the
      conclusion that disease-specific Tregs respond to tissue antigens to maintain
      physiological tolerance and prevent autoimmunity. First, polyclonal Tregs from
      antigen-positive donors suppress autoimmune ovarian disease (AOD) or experimental
      autoimmune prostatitis in day 3 thymectomized (d3tx) mice more efficiently than
      Tregs from antigen-negative donors. Second, Tregs of antigen-negative adult mice
      respond to cognate antigen in vivo and rapidly gain disease-specific Treg
      function. Third, in d3tx female recipients devoid of neonatal ovarian antigens,
      only female Tregs suppressed AOD; the male Tregs gain AOD-suppressing function by
      responding to the ovarian antigen in the recipients and mask the supremacy of
      female Tregs in AOD suppression. Fourth, when Tregs completely suppress AOD, the
      ovary-draining lymph node is the only location with evidence of profound and
      persistent (but reversible) host T-cell suppression. Fifth, from these nodes,
      highly potent AOD-suppressing Tregs are retrievable. We conclude that self
      tolerance involves the continuous priming of Tregs by autoantigens, and in
      autoimmune disease suppression, the effector T-cell response is continuously
      negated by potent disease-specific Tregs that accumulate at the site of
      autoantigen presentation.

PMID- 16903915
TI  - Transforming growth factor-beta and T-cell-mediated immunoregulation in the
      control of autoimmune diabetes.
AB  - It is now well-established that CD4+ regulatory T cells are instrumental in
      controlling immune responses both to self-antigens and to non-self-antigens.
      However, the precise modalities involved in their differentiation and survival,
      their mode of action and their antigen specificity are only partially understood.
      We have been particularly interested in the study of regulatory T cells
      controlling autoimmune insulin-dependent diabetes. Here, we provide evidence to
      support the phenotypic and functional diversity of regulatory T cells mediating
      transferable 'active' or 'dominant' peripheral tolerance in the non-obese
      diabetic mouse model (NOD). They include natural and adaptive regulatory T cells
      that are operational both in unmanipulated NOD mice and in animals undergoing
      treatments aimed at inducing/restoring tolerance to self-beta-cell antigens. At
      least in our hands, the differential cytokine-dependency appears as a major
      distinctive feature of regulatory T cells subsets. Among immunoregulatory
      cytokines, transforming growth factor-beta(TGF-beta) appeared to play a key role.
      Herein we discuss these results and the working hypothesis they evoke in the
      context of the present literature, where the role of TGF-beta-dependent T-cell
      mediated immunoregulation is still debated.

PMID- 16903916
TI  - Human regulatory T cells and their role in autoimmune disease.
AB  - As self-recognition is fundamental to the efficient operation of the immune
      system, a number of mechanisms have evolved to keep this potential pathologic
      self-reactivity in check. Thus, even though the majority of strongly self
      reactive T cells are deleted in the thymus during T-cell maturation, a number of
      mature T cells that recognize self-antigens can be found in the peripheral
      circulation in healthy individuals as well as in patients with autoimmune
      disease. These self-reactive cells are kept in a non-responsive state in healthy
      individuals while they appear to be involved in the etiology of a number of
      autoimmune diseases in patients. The primary role of a relatively recently
      identified T-cell population, referred to as natural CD4+ CD25+ regulatory T
      cells, is to modulate the activity of these self-reactive cells. Although it is
      still unclear how these regulatory cells function, they can inhibit the
      activation of other potentially pathologic T cells in in vitro assays. Using such
      assays, regulatory T cells isolated from patients with a number of autoimmune
      diseases have been shown to exhibit reduced inhibitory function as compared with
      those isolated from healthy individuals. In this review, we discuss human natural
      regulatory T cells, what is known about their function, and their associations
      with specific autoimmune diseases.

PMID- 16903917
TI  - Regulatory T-cell physiology and application to treat autoimmunity.
AB  - Endowed with the ability to actively suppress an immune response, regulatory T
      cells (Tregs) hold the promise of halting ongoing pathogenic autoimmunity and
      restoring self-tolerance in patients suffering from autoimmune diseases. Through
      many in vitro and in vivo studies, we have learned that Tregs can function in the
      lymph nodes as well as in the peripheral tissues. In vivo, Tregs act through
      dendritic cells to limit autoreactive T-cell activation, thus preventing their
      differentiation and acquisition of effector functions. By limiting the supply of
      activated pathogenic cells, Tregs prevent or slow down the progression of
      autoimmune diseases. However, this protective mechanism appears insufficient in
      autoimmune individuals, likely because of a shortage of Tregs cells and/or the
      development and accumulation of Treg-resistant pathogenic T cells over the long
      disease course. Thus, restoration of self-tolerance in these patients will likely
      require purging of pathogenic T cells along with infusion of Tregs with increased
      ability to control ongoing tissue injury. In this review, we highlight advances
      in dissecting Treg function in vivo in autoimmune settings and summarize multiple
      studies that have overcome the limitations of the low abundance of Tregs and
      their hypoproliferative phenotype to develop Treg-based therapies.

PMID- 16903918
TI  - The regulation of allergy and asthma.
AB  - Allergic diseases and asthma are caused by exaggerated T-helper 2 (Th2)-biased
      immune responses in genetically susceptible individuals. Tolerance to allergens
      is a mechanism that normally prevents such responses, but the specific
      immunological events that mediate tolerance in this setting are poorly
      understood. A number of recent studies indicate that regulatory T cells (Tregs)
      play an important role in controlling such Th2-biased responses. Tregs involved
      in regulating allergy and asthma consist of a family of related types of T cells,
      including natural CD25+ Tregs as well as inducible forms of antigen-specific
      adaptive Tregs. Impaired expansion of natural and/or adaptive Tregs is
      hypothesized to lead to the development of allergy and asthma, and treatment to
      induce allergen-specific Tregs could provide curative therapies for these
      problems.

PMID- 16903919
TI  - Regulatory T cells suppress systemic and mucosal immune activation to control
      intestinal inflammation.
AB  - The gastrointestinal (GI) tract is the main interface where the body encounters
      exogenous antigens. It is crucial that the local response here is tightly
      regulated to avoid an immune reaction against dietary antigens and commensal
      flora while still mounting an efficient defense against pathogens. Faults in
      establishing intestinal tolerance can lead to disease, inducing local and often
      also systemic inflammation. Studies in human as well as in animal models suggest
      a role for regulatory T cells (Tregs) in maintaining intestinal homeostasis.
      Transfer of Tregs can not only prevent the development of colitis in animal
      models but also cure established disease, acting both systemically and at the
      site of inflammation. In this review, we discuss the major regulatory pathways,
      including transforming growth factor-beta (TGF-beta), interleukin-10 (IL-10), and
      cytotoxic T-lymphocyte antigen-4 (CTLA-4), and their role in Treg-mediated
      control of systemic and mucosal responses. In addition, we give an overview of
      the known mechanisms of lymphocyte migration to the intestine and discuss how
      CD103 expression can influence the balance between regulatory and effector T
      cells. Further understanding of the factors that control the activity of Tregs in
      different immune compartments may facilitate the design of strategies to target
      regulation in a tissue-specific way.

PMID- 16903920
TI  - Regulatory T cells in virus infections.
AB  - This review discusses situations when the magnitude and function of immune
      responses to virus infection are influenced by regulatory T cells (Tregs). The
      focus is on CD4+ CD25+ forkhead box protein 3+ natural Tregs (nTregs). The immune
      response may be limited in magnitude and efficacy when animals with normal nTreg
      function are infected with virus. This limitation can be observed both in vitro
      and in vivo. In the case of herpes simplex virus (HSV), animals depleted of
      nTregs prior to infection more effectively control the virus. With some virus
      infections, Treg responses (either nTregs or interleukin-10-dependent adaptive
      Tregs) appear to contribute to immune dysfunction, accounting for viral
      persistence and chronic tissue damage. This may occur with hepatitis C virus and
      some retrovirus infections that include human immunodeficiency virus (HIV). Under
      other circumstances, the nTreg response is judged to be beneficial, as it may
      help limit the severity of tissue damage associated with an immunoinflammatory
      reaction to virus infection. Such a situation occurs in HSV-induced
      immunopathological lesions in the eye. With HIV, nTregs may help limit chronic
      immune activation that may precede collapse of the immune system. This review
      also discusses how virus infections become recognized by nTreg responses and how
      such responses might be manipulated to increase immunity or to limit virus
      induced immunopathology.

PMID- 16903921
TI  - Natural regulatory T cells and parasites: a common quest for host homeostasis.
AB  - This review discusses the roles played by natural CD4+ CD25+ regulatory T cells
      (natural Tregs) during parasitic infections. Natural Tregs may limit the
      magnitude of effector responses, which may result in failure to adequately
      control infection. However, natural Tregs also help to limit collateral tissue
      damage caused by vigorous antimicrobial immune responses. We discuss the
      hypothesis that parasites have evolved means to manipulate the host's natural
      Treg population, thereby generating conditions that secure survival in their
      vertebrate host for an extended period of time.

PMID- 16903922
TI  - Infectious tolerance and the long-term acceptance of transplanted tissue.
AB  - Short courses of antibody treatment aimed at blocking the coreceptors CD4 and CD8
      and/or costimulatory molecules such as CD40L are able to bring about long-term
      acceptance and tolerance of allogeneic transplants. This tolerant state is
      operational, in that potential effector cells remain but are tightly regulated
      through the induction of antigen-specific CD4+ regulatory T cells (Tregs). CD4+
      CD25+ FoxP3+ Tregs appear to play a prominent role, although other categories of
      Tregs have been documented. Transforming growth factor beta (TGFbeta) has been
      found to play a major role in the induction of the tolerant state with
      therapeutic antibodies as well as promoting the induction of FoxP3+ T cells from
      naive populations. The observation that Tregs can be found in tolerated grafts
      has led to the idea that they may interact with the grafted tissue to establish a
      state of acquired privilege symmetrical with a similar privileged
      microenvironment around antigen-presenting cells in lymphoid tissues. Dampening
      of aggressive immune responses by Tregs allows antigen to persist and be
      presented in an innocuous way to promote tolerance in new cohorts of T cells
      throughout the life of the tolerated graft. Regulation may operate at many stages
      of an immune response, even as a censor at the terminal differentiation stages of
      effector function.

PMID- 16903923
TI  - Dendritic cells expand antigen-specific Foxp3+ CD25+ CD4+ regulatory T cells
      including suppressors of alloreactivity.
AB  - Thymic derived naturally occurring CD25+ CD4+ T regulatory cells (Tregs) suppress
      immune responses, including transplantation. Here we discuss the capacity of
      dendritic cells (DCs) to expand antigen-specific Tregs, particularly polyclonal
      Tregs directed to alloantigens. Initial studies have shown that mature DCs are
      specialized antigen-presenting cells (APCs) for expanding antigen-specific CD25+
      CD4+ Tregs from TCR transgenic mice. When triggered by specific antigen, these
      Tregs act back on immature DCs to block the upregulation of CD80 and CD86
      costimulatory molecules. More recently, DCs have been used to expand alloantigen
      specific CD25+ CD4+ Tregs from the polyclonal repertoire in the presence of
      interleukin-2 (IL-2). Allogeneic DCs are much more effective than allogeneic
      spleen cells for expanding CD25+ CD4+ Tregs. The DC-expanded Tregs continue to
      express high levels of Foxp3, even without supplemental IL-2, whereas spleen
      cells poorly sustain Foxp3 expression. When suppressive activity is tested,
      relatively small numbers of DC-expanded CD25+ CD4+ Tregs exert antigen-specific
      suppression in the mixed leukocyte reaction (MLR), blocking immune responses to
      the original stimulating strain 10 times more effectively than to third party
      stimulating cells. DC-expanded Tregs also retard graft versus host disease (GVHD)
      across full major histocompatibility complex (MHC) barriers. In vitro and in
      vivo, the alloantigen-specific CD25+ CD4+ Tregs are much more effective
      suppressors of transplantation reactions than polyclonal populations. We suggest
      that the expansion of Tregs from a polyclonal repertoire via antigen-presenting
      DCs will provide a means for antigen-specific control of unwanted immune
      reactions.

PMID- 16903924
TI  - The role of regulatory T cells in alloantigen tolerance.
AB  - The diversification mechanism used by the adaptive immune system to maximize the
      recognition of foreign antigens has the side effect of generating autoreactivity.
      This effect is counteracted by deletion of cells expressing receptors with high
      affinity to self (central tolerance) and suppression of autoreactive cells by
      regulatory T cells (Tregs; peripheral tolerance). This understanding led to the
      notion that Tregs represent a specialized subset of autoreactive T cells with
      inhibitory function. The process of generating a diverse repertoire of receptors
      recognizing antigen presented by major histocompatibility complex (MHC)
      intrinsically leads to the generation of cells recognizing foreign MHC
      (alloantigen). The precursor frequency of T cells responding to alloantigen is
      substantially higher than that responding to any exogenous antigen. The only
      physiological context in which this becomes a problem is placental viviparity.
      Although the maternal immune system has no intrinsic mechanism to distinguish
      between a pathogen and paternally derived fetal alloantigen, it has to neutralize
      the former and tolerate the latter. We review the function of Tregs from this
      perspective and propose that they may have evolved to promote tolerance to
      alloantigen in the context of pregnancy.

PMID- 16903925
TI  - Abstracts of the 2nd Biennial Conference of the International Society for Bipolar
      Disorders, Edinburgh, Scotland, 2-4 August 2006.

PMID- 16903926
TI  - High-dose chemotherapy for male germ cell tumor.
AB  - Today, 20-30% of male patients with advanced germ cell tumor (GCT) do not have
      durable, complete remission in spite of cis-platinum (CDDP)-based chemotherapy.
      High-dose chemotherapy (HDCT) has been tried in CDDP refractory GCT patients.
      Initially HDCT was performed with autologous bone marrow transplantation in
      heavily treated patients. However, the clinical outcome was not good and the
      treatment-related death rate was not ignorable. Therefore, earlier introduction
      of HDCT with peripheral blood stem cell transplantation was preferable as it
      renders HDCT more effective and less toxic, and multicycle HDCT is feasible. The
      durable free rate of recent HDCT for refractory GCT patients is 32-65%. HDCT is
      also performed as first line chemotherapy for poor prognosis GCT patients.
      Induction chemotherapy followed by multicycles of HDCT was tried. The durable
      free rate of recent HDCT as first line chemotherapy is 43-73%. Although previous
      reports suggest the superiority of HDCT, one recent randomized controlled trial
      (RCT) failed to show an improvement with one cycle of HDCT followed by three
      cycles of standard-dose chemotherapy (SDCT) compared with four cycles of SDCT.
      Ongoing RCT comparing multicycles of HDCT with SDCT for poor prognostic GCT
      patients will clarify the role of HDCT. Recently, new regimens of HDCT containing
      paclitaxel have been devised. In this review, the history, current status and
      future of HDCT for advanced or refractory GCT will be discussed.

PMID- 16903927
TI  - Renal cell carcinoma in dialysis patients: a single center experience.
AB  - AIM: Renal cell carcinoma (RCC) is a life-threatening complication of end-stage
      renal disease with an unclear pathogenesis. We evaluated RCC developing in
      patients undergoing dialysis. METHODS: In 2624 patients undergoing hemodialysis
      or continuous ambulatory peritoneal dialysis at our hospital between July 1993
      and March 2004, we performed annual screening for RCC using abdominal computed
      tomography and ultrasonography. Patients diagnosed with RCC underwent radical
      nephrectomy as well as clinical and pathologic evaluation. RESULTS: RCC was
      detected in 44 patients (1.68%; 31 males and 13 females). The age of RCC patients
      was 55.5 +/- 11.1 years. Dialysis duration before RCC diagnosis was 11.2 +/- 7.2
      years. Most RCC were early stage and low stage by TNM classification, 43 patients
      had N0M0 RCC, whereas one had N1M0. Tumor size was 2.9 +/- 1.9 cm. The
      predominant histological type of RCC was common or conventional cell-type
      carcinoma (clear cell carcinoma and granular cell carcinoma). Of patients,
      5(11.4%) had bilateral RCC, and satellite tumor lesions in RCC were detected in
      13 (29.5%). In 36 patients (81.8%) RCC was accompanied by acquired cystic disease
      of the kidney. These patients had longer dialysis durations (P = 0.01) and
      smaller tumors (P = 0.048). RCC metastasized postoperatively in 4 patients
      (9.1%), while one (2.3%) died of cancer. CONCLUSIONS: Our dialysis patients
      showed a higher incidence of RCC than the general population. Prognosis was
      favorable because tumors were detected by screening when they were small.
      Therefore, periodical screening for RCC seems very important in dialysis
      patients.

PMID- 16903928
TI  - Papillary renal cell carcinoma: a clinicopathological study of 35 cases.
AB  - AIM: The objective of the present study was to characterize the
      clinicopathological features of histologically defined papillary renal cell
      carcinoma (RCC). METHODS: The present study included a total of 35 patients who
      were treated by radical surgery and subsequently diagnosed as having papillary
      RCC between April 1995 and June 2004. Clinicopathological data of these patients
      were retrospectively reviewed according to the previously reported classification
      system (Mod. Pathol. 1997; 10: 537-44). RESULTS: Of these 35 patients, 23 (65.7%)
      and 12 (34.3%) were diagnosed as type 1 and type 2 papillary RCC, respectively.
      Despite the lack of significant differences in clinical parameters between these
      two groups, including age, gender, clinical stage and metastasis, the incidence
      of symptomatic disease in patients with type 2 papillary RCC was significantly
      higher than that in those with type 1 papillary RCC. Pathological examinations
      demonstrated that there were no significant differences between these two groups
      in pathological stage, tumor grade or vascular invasion. Furthermore, there was
      no significant difference between these two groups in overall or recurrence-free
      survival. CONCLUSIONS: Although the present study included a small number of
      patients with short follow-up period, the clinicopathological features including
      prognoses were almost similar between patients with type 1 and type 2 papillary
      RCC; therefore, careful postoperative follow-up should be considered for patients
      with papillary RCC irrespective of morphological subtype.

PMID- 16903929
TI  - Pathophysiology and subjective symptoms in women with impaired bladder emptying.
AB  - AIM: To assess the pathophysiology and subjective symptoms in female patients
      with impaired bladder emptying. METHODS: Eighty-three consecutive female patients
      attending a urology clinic with postvoid residual urine of more than 100 mL were
      recruited. Free uroflowmetry, measurement of postvoid residual urine and pressure
      flow study were performed in all patients. The detailed assessment of subjective
      symptoms and their bothersomeness to the patients were assessed using a self
      administered questionnaire comprising 12 items: five associated with voiding
      symptoms, five with storage symptoms, and two with discomfort and pain on
      voiding. The questionnaire was applied to 83 patients with impaired bladder
      emptying, 41 patients with urinary incontinence, and 21 normal controls. RESULTS:
      Although 77% of the patients with impaired bladder emptying consulted a urology
      clinic because of voiding symptoms, the remaining 23% complained of storage
      symptoms or symptoms other than lower urinary tract symptoms (LUTS). The pressure
      flow study revealed the pathophysiology of impaired bladder emptying as impaired
      detrusor contraction in 68 patients (81.9%), and bladder outlet obstruction in 12
      patients (14.8%). The assessment of subjective symptoms using the questionnaire
      revealed that the patients with urinary incontinence showed a high frequency only
      in storage symptoms; however, those with impaired bladder emptying revealed a
      high frequency not only in voiding but also in storage symptoms. CONCLUSIONS:
      Female patients with impaired bladder emptying present with a wide range of lower
      urinary tract symptoms associated with both voiding and storage symptoms. To
      determine an appropriate treatment modality, the correct diagnosis of the
      underlying pathophysiology of impaired bladder emptying by pressure-flow study is
      of primary importance.

PMID- 16903930
TI  - Significant relationship of time-dependent uroflowmetric parameters to lower
      urinary tract symptoms as measured by the International Prostate Symptom Score.
AB  - AIMS: The aim of the present paper is to elucidate the possible involvement of
      time-dependent parameters as obtained by uroflowmetry in the manifestation of
      lower urinary tract symptoms (LUTS) in elderly patients. METHODS: Using simple
      and multiple regression analyses, the correlation of the International Prostate
      Symptom Score (IPSS) with objective parameters including age, postvoid residual,
      uroflowmetry and transrectal ultrasonic measurements of the prostate was analyzed
      in 206 male patients (average age of 68.0 +/- 7.4 years) who visited our
      outpatient clinic complaining of LUTS. RESULTS: In the 206 patients, the mean
      maximum flow rate was 12.2 mL/s (13.7 mL/s in mild, 11.9 mL/s in moderate, and
      11.2 mL/s in severe IPSS total score) and average flow rate was 4.4 mL/s (5.4
      mL/s in mild, 4.3 mL/s in moderate, and 3.5 mL/s in severe IPSS total score).
      Simple regression analyses demonstrated that age, voiding time, and average and
      maximum flow rates correlate significantly with symptom scores. In particular,
      relatively strong relationships were found between average flow rate and scores
      of intermittency, weak stream and total and voiding symptoms scores. Serum
      prostate specific antigen level, postvoid residual and prostatic ultrasonic
      measurements did not show a significant correlation with symptom scores. Multiple
      regression analyses revealed age and average flow rate to be independent
      determinants for symptom scores. These results suggest that the time-dependent
      function in micturition interferes in the manifestation of LUTS in elderly men
      who have borderline or pathologic maximum flow rate. When evaluating uro
      flowmetry in elderly male patients with LUTS, attention should be paid to time
      dependent parameters such as voiding time and average flow rate.

PMID- 16903931
TI  - Vardenafil 20-mg demonstrated superior efficacy to 10-mg in Japanese men with
      diabetes mellitus suffering from erectile dysfunction.
AB  - AIM: Vardenafil is a highly selective and potent phosphodiesterase type-5
      inhibitor for the treatment of erectile dysfunction (ED). The efficacy of
      vardenafil has been demonstrated in a broad range of ED populations, but has not
      yet been assessed in Japanese patients with diabetes mellitus (DM), although DM
      is frequently associated with difficult-to-treat ED. This is the first study to
      investigate whether high-dose vardenafil (20 mg) can demonstrate superior
      efficacy to the usual dose (10 mg) in this subpopulation in Japan. METHODS: The
      study was a randomized, placebo-controlled, double-blind, multi-centre, parallel
      group comparison 12-week study. Following 4 weeks observation period, 778
      patients aged 26-64 years old with ED and DM (HbA1c >12% at screening was
      excluded) both of more than 3 years duration were randomly allocated to one of
      the three groups, vardenafil 10 mg, 20 mg, or placebo (randomization ratio
      3:3:1). Erectile function (EF) domain score of the International Index of
      Erectile Function was estimated as the primary efficacy parameter. RESULTS:
      Vardenafil 10 and 20 mg both significantly improved the EF domain score from 13.6
      and 13.9 at baseline to 21.8 and 22.9 at last observation carried forward (LOCF),
      respectively, compared to placebo (13.7 at baseline to 16.3 at LOCF; p<0.0001).
      In addition, vardenafil 20 mg demonstrated superior efficacy to 10 mg (p<0.05),
      and the difference was more evident in severe ED patients (baseline EF domain
      score <11). The safety profile was comparable between these two doses (drug
      related adverse events: 6.6, 22.0 and 24.2% in placebo, vardenafil 10 mg, and 20
      mg arms, respectively). The most common adverse events were hot flush, headache
      and nasal congestion, which were mild in intensity and transient, and are known
      to be common to PDE5 inhibitors. CONCLUSION: In Japanese men with DM and ED,
      vardenafil 10 mg and 20 mg were effective in improving erectile function with
      comparable safety profiles. Vardenafil 20 mg demonstrated superior efficacy
      compared with 10 mg, suggesting incremental clinical benefit in using the higher
      dose in this difficult-to-treat population.

PMID- 16903932
TI  - Color Doppler ultrasonography as a routine clinical examination in male
      infertility.
AB  - AIM: We assessed the value of scrotal color Doppler ultrasonography as a routine
      examination in infertile men. METHODS: Color Doppler ultrasonography was
      performed in 545 infertile men with a mean age of 35.8 years to detect
      intrascrotal abnormalities. Findings were compared with those of physical
      examination. RESULTS: Intrascrotal abnormalities were detected by ultrasonography
      in 65.3% of patients. Of 374 abnormalities, 58.3% were undetected by physical
      examination. Left varicocele was found in 313 patients (57.4%); testicular
      microlithiasis in 30 (5.5%); epididymal cyst in 21 (3.9%); right varicocele in 4
      (0.8%); and testicular cysts in 3 (0.6%). One occurrence each (0.2%) was found
      for testicular tumor, intrascrotal hemangioma, and hydrocele of the spermatic
      cord. Compared to ultrasonography, sensitivity in detecting left varicocele by
      physical examination was 58.4%; specificity, 79.3%; accuracy, 67.3%; and positive
      predictive value, 79.3%. Venous diameters in the pampiniform plexus were 3 mm or
      more in 61.5% of 130 subclinical left varicoceles. Of 30 patients with testicular
      microlithiasis, 14 had varicocele, 2 had epididymal cyst,s 3 had a history of
      mumps orchitis, 1 had retractile testis, and 1 had a history of orchiectomy for
      contralateral testicular tumor. CONCLUSIONS: The routine Color Doppler
      ultrasonography is valuable for diagnosing scrotal abnormalities in infertile
      men, frequently detecting non-palpable lesions.

PMID- 16903933
TI  - Can the levels of nitric oxide in the urine, serum and tumor tissue be putative
      markers for bladder cancer?
AB  - AIM: To determine nitric oxide (NO) levels in serum, urine, tumor tissue and non
      malignant adjacent tissue in bladder cancer patients compared with those in
      patients with a non-neoplastic genitourinary disease and to evaluate
      postoperative serum and urine NO change. METHODS: Samples was collected in 20
      cancer and 41 control patients. Griess reagent was used for NO measurements.
      RESULTS: Mean age in the cancer and control groups was 64.2 +/- 9.9 and 63.7 +/-
      8.9 years, respectively. Preoperatively, urinary infection incidence was not
      statistically different between groups. There were no significant differences in
      serum, urine and tissue NO levels in patients with and without infection in both
      groups. Hematuria was found to not affect urine NO level in the cancer group.
      Urine NO level was significantly higher than in controls preoperatively,
      decreased significantly following operation and remained stable after the third
      month. High serum NO values decreased at the early postoperative period; however,
      they re-increased in the long-term. No significant differences were observed in
      the third month in serum and urine NO levels between the patients with (no. 6)
      and without (no. 14) residual or relapsing tumor. No statistical difference was
      observed between NO levels in non-malignant adjacent and control tissues.
      However, tumor tissue NO level was significantly higher than those in the other
      two. There were no statistical differences in the first and third month serum and
      urine NO levels between patients who underwent bacillus Calmette-Guerin
      instillation therapy postoperatively and the patients who took chemotherapy or no
      further treatment. CONCLUSIONS: Both local and generalized host defense
      mechanisms seem to function in bladder cancer patients. Although further
      evaluation with a longer observation period and larger numbers of patients is
      necessary, results suggest that serum and urine NO levels are not putative and
      useful markers for bladder cancer.

PMID- 16903934
TI  - Inhibition of 5-lipoxygenase pathway suppresses the growth of bladder cancer
      cells.
AB  - AIM: Many stimuli, including growth factors and cytokines, activate arachidonic
      acid (AA) metabolic pathways, which are involved in cancer development and
      progression. We examined the effects of a series of pharmacological inhibitors of
      AA metabolic enzymes on bladder cancer cells to determine the role of AA pathway
      in this malignancy. METHODS: Human bladder cancer cell lines were treated with
      various AA metabolic enzymes inhibitors for lipoxygense (LOX) and cyclooxygenase
      (COX) pathways, and the growth suppression effects were examined. The enzyme
      expression in cancer cells was examined by immunoblot analyses. RESULTS: A 5-LOX
      specific inhibitor, AA861, dose-dependently inhibited the growth of bladder
      cancer cells. The growth inhibitory effects were greatly abolished by 5-LOX
      product, 5-HETE, but not by other LOX products examined. They were observed in
      four cancer cells that expressed 5-LOX, but not in one that did not. Of a series
      of LOX and COX pathway inhibitors, AA861 was the strongest one to suppress the
      growth of cancer cells. CONCLUSIONS: Bladder cancer cells frequently expressed 5
      LOX. A 5-LOX-specific inhibitor, AA861, revealed the strongest growth suppression
      of those cells compared to other LOX and COX pathway inhibitors, and the growth
      suppression effects were considered to be due to inhibition of the enzymatic
      activity. Therefore, 5-LOX may play a regulatory role in proliferation and/or
      survival of bladder cancer, and may be a therapeutic target for the disease.

PMID- 16903935
TI  - Clinical value of vesical leukoplakia and evaluation of the neoplastic risk by
      mutation analyses of the tumor suppressor gene TP53.
AB  - AIM: Leukoplakia has been found to be precancerous in organs covered with
      squamous epithelium. The present study was conducted to determine whether
      leukoplakia described in the female bladder is also a premalignant lesion.
      METHODS: Between 1973 and 1996, 77 female patients were diagnosed with vesical
      leukoplakia by cystoscopy and cytology and were followed-up until 2004 (mean
      follow-up time: 8.3 years). A survey was conducted to analyze exposure to
      cocarcinogens. Additionally, DNA was isolated from 36 urine sediments and
      analyzed for TP53 mutations. The results were compared to the mutation frequency
      of TP53 in urine sediments from patients diagnosed with transitional cell
      carcinoma (TCC) of the bladder and healthy controls. RESULTS: The whitish lesion
      was mostly located at the trigone and varied in size and location during the
      follow-up years. TP53 mutations were detected in 6 out of 36 urine samples in
      exons 5, 6 and 7 (mutation frequency: 16.7%). Among control patients with no
      leukoplakia or TCC of the bladder (n = 70), the spontaneous mutation frequency
      was similar (14.3%). In contrast, the mutation frequency in patients with TCC of
      the bladder (n = 148) revealed 39.9% in exons 5, 6, 7 and 8. The present study
      did not show any statistically significant correlations between chronic
      inflammations, TP53 mutations, exposure to carcinogens and vesical leukoplakia.
      CONCLUSIONS: Our data suggest that vesical leukoplakia does not necessarily hold
      neoplastic potential and needs to be clearly distinguished from leukoplakia in
      other localizations. Therefore, we suggest that a biopsy can be omitted, if
      follow-up controls by cystoscopy are performed regularly.

PMID- 16903936
TI  - Lower urinary tract symptoms and risk of prostate cancer in Japanese men.
AB  - Our aim was to investigate whether or not men with lower urinary tract symptoms
      are at increased risk of prostate cancer. A total of 3511 men aged 50-79 years
      who underwent mass screening for prostate cancer between 2002 and 2004 for the
      first time, and completed the International Prostate Symptom Score (IPSS)
      questionnaire at the time of the prostate specific antigen (PSA) test, were
      enrolled in the present study. All men with PSA values greater than 4.0 ng/mL
      were advised and encouraged to undergo transrectal systematic sextant biopsy. The
      number of cancers subsequently detected was compared between men with IPSS scores
      of 0-7 and 8-35. Of the 3511 men, 219 (6.2%) had PSA values greater than 4 ng/mL,
      178 (5.1%) underwent biopsy, and 51 (1.5%) were found to have prostate cancer.
      Although the PSA positivity rate for men with IPSS scores of 8-35 was
      significantly higher than that in the 0-7 group, there were no significant
      intergroup differences in the cancer detection rates for biopsied men and for
      total screened subjects. Multivariate logistic regression analysis revealed that
      prostate volume was the dominant predictor for the detection of prostate cancer,
      followed by PSA level, but the IPSS made no significant contribution. No
      significant difference was noted in the IPSS scores between men with cancer and
      the others of the same age group. Symptomatic Japanese men are not at higher risk
      of prostate cancer despite their higher PSA values compared with asymptomatic men
      of the same age group.

PMID- 16903937
TI  - Testosterone administration promotes regeneration of chemically impaired
      spermatogenesis in rats.
AB  - AIM: It has been proposed that gonadotropin-releasing hormone (GnRH) analog
      administered after testicular damage stimulates the recovery of spermatogenesis.
      However, GnRH analogs suppress the function of sex accessory organs. In this
      study, we investigated whether testosterone also stimulates the regeneration of
      rat spermatogenesis after exposure to busulfan. METHODS: Male Fisher rats were
      divided into three groups of five each and all rats were treated with busulfan,
      25 mg/kg, intraperitoneally at week 0. Group A served as the control. The other
      two groups received testosterone enanthate, 8 mg/kg, subcutaneous injections at 3
      week intervals two times before (group B) or three times after (group C)
      busulfan. States of spermatogenesis were evaluated by histology and by the number
      of spermatid nuclei per testis at week 25. RESULTS: The mean percentage of
      'recovered' seminiferous tubules plus or minus standard deviation was 10.3 +/-
      7.8% in group A and 2.1 +/- 1.2% in group B. In both groups, more than 80% of the
      tubules remained degenerated. However, testes of group C rats showed an
      improvement of up to 37.1 +/- 20.5% (P < 0.05). The significant recovery of
      spermatogenesis was also demonstrated in group C by counting the number of
      spermatid nuclei per testis ([78.8 +/- 57.5] x 106). However, the count was only
      (7.6 +/- 13.5) x 106 and (0.52 +/- 1.0) x 106 in group A and B, respectively.
      CONCLUSIONS: Testosterone administration after severe testicular damage enhanced
      the regeneration of spermatogenesis in rats. We assumed that supplementary doses
      of testosterone would be more practical for clinical application than GnRH
      analogs, because exogenous testosterone maintains androgenicity.

PMID- 16903938
TI  - Atypical findings in a patient with a renal milky stone including a cake of
      stone.
AB  - A 54-year-old woman was admitted to our department with the diagnosis of a renal
      calculus. She exhibited dull left flank pain. A plain film revealed a round
      opaque calcific density in the left kidney in the supine and the upright
      position. There was no connection between the calcification and the renal
      collecting system by retrograde pyelography. Computed tomography in the supine
      position showed a rounded calcification in the left renal parenchyma without a
      semilunar configuration. She was diagnosed with left renal calyceal diverticula
      calculi. She underwent a surgical intervention which found a renal milky stone
      including a 10-mm. diameter stone. The examination of the fluid and the stone
      material disclosed three components: calcium phosphate, calcium oxalate and
      calcium carbonate. The present case is interesting because its characteristics
      differ from the common features of renal milky stone.

PMID- 16903939
TI  - Early diagnosis and straight forward surgery of an asymptomatic primary
      angiosarcoma of the kidney led to long-term survival.
AB  - We report the first case of a diagnosis of an asymptomatic primary renal
      angiosarcoma. The patient underwent laparoscopic nephrectomy and is alive after
      long-term follow up. We provide the preoperative imaging studies and the
      histologic features of this exceedingly rare tumor.

PMID- 16903940
TI  - Late caliceal fistula after kidney transplantation.
AB  - Caliceal fistula is a rare urological complication that can occur usually shortly
      after kidney transplantation (KTx). The occlusion of the renal accessory artery
      with subsequent necrosis of the kidney pole is the most common cause of the
      fistula development. We report a case of a 57-year-old man with reconstruction of
      two accessory renal arteries by anastomosis to the side of the main artery during
      graft placement complicated by late caliceal fistula, managed surgically.
      Directly after KTx good kidney graft function (serum creatinine concentration 151
      micromol/L) was observed. The patient noticed protuberance and pain in the kidney
      graft area 5 months later. Diagnostic imaging revealed moderate urostasis and
      liquid collection in the region of the lower graft pole. Administration of a
      contrast medium through the inserted drain visualized a fistula of a lower renal
      calyx and ureteric stenosis. Percutaneous drainage was applied with subsequent
      stop of diuresis through the urethral catheter. During the surgery, the resection
      of a lower kidney graft pole necrosis was performed, with the closure of caliceal
      fistula. Simultaneously double pigtail ureteric stent was inserted. After the
      next two months the pigtail catheter was removed, and neither urostasis in the
      kidney graft nor liquid collection in the perigraft area were observed. The
      exceptionality of the case is the late caliceal fistula occurrence. We may only
      speculate, why it happened 5 months after KTx. The thrombosis of stenosed
      accessory artery is the most probable cause.

PMID- 16903941
TI  - Accidental dislocation of an intracaval temporary filter into the heart in a case
      of renal cell carcinoma extending into the vena cava.
AB  - In a case of renal cell carcinoma extending into the vena cava, a temporary
      intracaval filter was applied before surgery to prevent pulmonary artery
      thrombosis. Two days later, the filter accidentally migrated into the right
      ventricle during defecation. Fortunately, it was successfully removed without
      damaging cardiac musculature under fluoroscopy.

PMID- 16903942
TI  - Acute renal failure as a result of bilateral ureteral obstruction by Candida
      albicans fungus balls.
AB  - A 73-year-old male with a history of diabetes mellitus was admitted to our
      hospital for acute renal failure. An ultrasonogram revealed bilateral
      hydronephrosis, which worsened despite insertion of a bladder catheter.
      Nephrostomy catheters were positioned bilaterally, and Candida albicans was found
      in the urine culture. The patient was successfully treated with intermittent
      direct irrigation and i.v. antifungal agent therapy. Since 1977, approximately 50
      cases of fungus balls or fungal bezoars in the urinary tract have been reported,
      but the majority of these cases have been characterized by unilateral ureteral or
      bladder involvement. Herein, we report a case of acute renal failure as a result
      of bilateral ureteral obstruction by Candida albicans fungus balls.

PMID- 16903943
TI  - Complete response of a recurrent advanced urachal carcinoma treated by S
      1/cisplatin combination chemotherapy.
AB  - We report a case of recurrent advanced urachal carcinoma with right internal
      iliac node and left lung metastases in a 34-year-old man. After receiving partial
      cystectomy including en bloc resection of the urachus and with bilateral pelvic
      lymph node dissection, he was treated with five courses of S-1 and cisplatin
      combination chemotherapy. He remains free from the disease after a 30-month
      follow-up period. S-1/cisplatin combination chemotherapy is suggested to be a
      potent tool for controlling advanced urachal carcinoma.

PMID- 16903944
TI  - Possible involvement of bone morphogenetic protein 2 in heterotopic ossification
      in metastatic lesion from urothelial carcinoma of bladder.
AB  - Heterotopic bone formation caused by urothelial carcinoma is rare. The precise
      mechanism of heterotopic ossification is still unknown. We report a case of
      urothelial carcinoma with heterotopic bone formation in a metastatic site and
      investigate the expression of bone morphogenetic protein 2 (BMP-2) and the BMP
      receptor (BMPR)-Ib using immunohistochemistry. Positive staining of BMP-2 was
      observed in the cytoplasm of tumor cells in both bladder and psoas lesions. In
      addition, positive staining of BMPR-Ib was seen in osteoblast-like cells adjacent
      to bone formation in the psoas metastasis. The heterotopic ossification may
      result from the metaplasia of pluripotent stem cells into osteoblast cells
      induced by BMP-2 in a paracrine fashion.

PMID- 16903945
TI  - Complete covered duplication of the bladder, urethra, vagina, uterus and visceral
      sequestration.
AB  - We report a rare case of female covered exstrophy with complete duplication of
      the lower genitourinary tract and visceral sequestration, unassociated with other
      congenital anomalies. To our knowledge the occurrence of this anomaly with
      complete urinary continence has not been reported previously.

PMID- 16903946
TI  - Severe eosinophilic cystitis in a woman with anorexia nervosa.
AB  - Eosinophilic cystitis is a rare inflammatory disorder. It is considered to be
      self limiting necessitating only supportive therapy. Surgical intervention is
      unusual. We report here an association between eosinophilic cystitis and anorexia
      nervosa in an adult woman requiring radical surgery for progressive relentless
      disease. Estrogen deficiency associated with a possible allergic etiology could
      explain this association.

PMID- 16903947
TI  - Tubulovillous adenoma developing after urinary reconstruction using ileal
      segments.
AB  - A case of tubulovillous adenoma arising in an augmented bladder is described.
      Ureteroileal substitution and ileocystoplasty was performed when the patient was
      18 years old. She noticed gross hematuria 44 years after the surgery. Cystoscopy
      revealed a non-papillary multiple tumor at the site of ileovesical anastomosis
      and transurethral resection biopsy was performed. Histopathological examination
      revealed a tubulovillous adenoma. A tubulovillous adenoma developing at the
      augmented bladder is rare. To our knowledge, this is the second case in which a
      tubulovillous adenoma developed in an augmented bladder.

PMID- 16903948
TI  - Testicular metastasis of transitional cell carcinoma of the urinary bladder: an
      unusual site.
AB  - We present a 74-year-old man with a testicular metastasis originating from a
      transitional cell carcinoma of the urinary bladder. Initially, radical cystectomy
      and ileal-conduit urinary diversion were performed. Three years later, he
      presented with a tumor in the left testicle, proved to harbor transitional cell
      carcinoma.

PMID- 16903949
TI  - Cystadenoma of the seminal vesicle.
AB  - Primary tumors of the seminal vesicle are quite rare with most reported cases
      being carcinomas. However, benign tumors of the seminal vesicle are extremely
      rare. We report a case of a cystadenomas of the seminal vesicles in a 46-year-old
      asymptomatic man, which was detected incidentally by computed tomography.

PMID- 16903950
TI  - Laparoscopic management of a retained heavily encrusted ureteral stent.
AB  - The indwelling ureteral stent is a fundamental part of today's urologic practice.
      Since its introduction in 1978, many improvements have been made in stent design
      and composition to minimize patient discomfort. As a consequence, the patient can
      forget about the stent. A known and well-documented complication of this
      situation is encrustations of the ureteral stent which causes significant
      morbidity to the patient, and at times, they are very difficult to manage.
      Reports in the literature describe techniques that require several procedures and
      anaesthetic sessions to effect stent extraction. Here, we report the one-sitting
      laparoscopic management of a heavily encrusted and stuck DJ stent, with minimal
      morbidity and very short hospital stay. Laparoscopic management of this common
      urologic problem has not been reported before. A comprehensive discussion is also
      presented regarding the management of such problems and their prevention.

PMID- 16903951
TI  - En bloc mobilization of the inferior vena cava and large hypervascular right
      renal tumors with or without inferior vena cava thrombus: Posterior ligation of
      the renal artery.
AB  - We describe our approach of posterior ligation of the renal artery during
      resection of large hypervascular right renal tumors. This technique uses en bloc
      mobilization of the inferior vena cava and renal tumor to ligate the renal artery
      at its origin from the aorta. In our experience, the use of this posterior
      approach for renal artery ligation is safe and effective, even with large renal
      tumors with multiple collaterals and/or lymph nodes making the identification of
      the renal artery difficult.

PMID- 16903952
TI  - Clinical research of renal vein control using Hem-o-lok clips in laparoscopic
      nephrectomy.
AB  - Control of the renal vein represents a crucial step in laparoscopic nephrectomy.
      Although endovascular gastrointestinal anastomosis (GIA) staplers have generally
      been used for renal vein control because of the large diameter of the vessel, Hem
      o-lok clips have recently been used for renal artery control. GIA staplers are
      expensive and can malfunction on rare occasions, resulting in severe
      complications. We evaluated renal vein control using Hem-o-lok clips (adaptive
      vascular width 7-16 mm) in laparoscopic nephrectomy. Since April 2004, we have
      ligated renal arteries using Hem-o-lok clips. From June 2004, this method was
      applied for renal vein control in 40 laparoscopic nephrectomies. After renal
      pedicle dissection, renal pedicle ligation was accomplished using extra large
      (XL) Hem-o-lok clips on both the renal arteries and veins by placing two clips on
      the patient side and one clip on the specimen side. Ligation times for obtaining
      renal vein control were compared between XL Hem-o-lok clips and GIA staplers in
      40 cases before June 2004. Vascular control using XL Hem-o-lok clips was
      successful in all 40 cases, without any slipping of clips or uncontrolled
      bleeding. After renal pedicle dissection, ligation time for achieving renal vein
      control was 167.0 +/- 48 s (range: 122-295 s) using XL Hem-o-lok clips (mean,
      three clips) and 68 +/- 24.0 s (range: 54-150 s) using a GIA stapler. XL Hem-o
      lok clips allow safe and reliable control of renal veins in laparoscopic
      nephrectomy. Ligation time is only 100 s longer than using a GIA stapler. In
      addition, costs are reduced by more than 90% compared to GIA stapling.

PMID- 16903953
TI  - Midline extraperitoneal approach to upper urinary tract surgery: anatomical basis
      of surgical technique.
AB  - AIM: To overcome the disadvantages inherent in the standard surgical approach to
      the kidney, we introduced a novel surgical technique via a midline
      extraperitoneal approach. The surgical technique is not substantially different
      from that of the standard midline transperitoneal approach, except no entry is
      made into the peritoneal cavity. Although the peritoneum itself is extremely thin
      and fragile, the peritoneum together with underlying subperitoneal fascia can be
      dissected readily as a substantial layer, if the proper plane is dissected.
      Further medial mobilization of the peritoneal sac en bloc by pursuing the fusion
      fascia plane allows full exposure of the kidney, ureter and great vessels. This
      approach was adopted for consecutive 51 patients during a 10-month period in
      2003. All operations, including 33 radical nephrectomies and 11
      nephroureterectomies were completed successfully without significant technical
      difficulties and differences in operation time and estimated blood loss compared
      to the transperitoneal approach. No intra- or perioperative complication
      occurred. All patients did seem to have a much more comfortable postoperative
      period with minor pain and few abdominal complaint, and the clinical impression
      was that they resumed the physical activity and oral intake earlier than those
      after the transperitoneal approach (P = 0.056). There are no operation-related
      problems such as intra-abdominal adhesion or abdominal muscle weakness resulting
      in some deformity at 2-year or more follow up. This approach combines the
      advantages of the transperitoneal midline and extraperitoneal flank approach. Its
      use will undoubtedly reduce the complications inherent in the transperitoneal
      approach or the flank approach.

PMID- 16903954
TI  - Automatic switching and guidance system to facilitate unassisted uroflowmetry
      using commercial electronic devices.
AB  - To enable male patients to undergo uroflowmetry in a private condition without
      medical supervision, we devised an automatic switching and patient guidance
      system for the spinning disk uroflowmeter Urodyn 1000, using two commercial
      electronic devices (an infrared motion sensor tap and a memorizable vacuum
      fluorescent display). Instead of running the uroflowmeter continuously, which
      shortens the life of the spinning disk due to mechanical wear, an infrared motion
      sensor turns on the devices each time a patient enters the room. The patient
      urinates according to the timely instructions on the visible display and voided
      urine directly flows into a urinal. The devices are automatically turned off 5
      min after the patient leaves the room. With the use of our system, men already
      acquainted with uroflowmetry could perform self-administered uroflowmetry any
      time in private. The system was considered useful for improving the quality of
      patient service.

PMID- 16903955
TI  - Application of siphon principle to fluid drainage in transurethral surgery.
AB  - Transurethral resection is usually performed using an all-in-one drape with a
      fluid collection pouch, drainage port and hose. Gravity drainage of irrigation
      fluid through the hose is often hampered, resulting in fluid retention in the
      pouch. We applied a siphon principle to facilitate fluid drainage by making a U
      shaped bend near the distal end of the hose, using an adhesive tape, and hooking
      the distal end of inverted U shape on the edge of bucket placed on the floor.
      When the hose is filled with irrigation fluid up to the crest of the siphon,
      fluid flow driven by atmospheric pressure continues until the pouch is evacuated.
      Repriming and restarting occur automatically throughout the operation. This
      simple device has virtually eliminated fluid retention in the pouch and proved to
      be especially useful in transurethral prostatectomy, which requires a large
      amount of irrigation fluid.

PMID- 16903956
TI  - XXIXth International Congress of the International Society of Blood Transfusion,
      Cape Town, South Africa, 2-7 September, 2006. Abstracts.

PMID- 16903957
TI  - Fibrillating areas isolated within the left atrium after radiofrequency linear
      catheter ablation.
AB  - INTRODUCTION: Nonpulmonary vein sources have been implicated as potential drivers
      of atrial fibrillation (AF). This observational study describes regions of
      fibrillating atrial tissue isolated inadvertently from the left atrium (LA)
      following linear catheter ablation for AF. METHODS AND RESULTS: We report four
      patients with persistent/permanent AF who underwent pulmonary vein isolation with
      additional linear lesions and who presented with recurrent AF (mean AF cycle
      length [AFCL] 175-270 ms). Further catheter ablation resulted in the inadvertent
      electrical isolation of significant areas of the LA in which AF persisted at the
      same AFCL as was measured prior to disconnection, despite the restoration of
      sinus rhythm (SR) in all other left and right atrial areas, strongly suggesting
      that these islands were driving the remaining atria into fibrillation. The
      disconnected areas were located in the lateral LA, including the left atrial
      appendage (LAA) in three patients (limited to the LAA in one) and in the
      posterior LA in one patient. These isolated fibrillating regions represented 15
      24% of the global LA surface, as estimated by electroanatomic mapping.
      CONCLUSION: Fibrillation can be maintained within electrically isolated regions
      of the LA following catheter ablation of AF, demonstrating the importance of
      atrial drivers in the maintenance of AF. Further mapping of these drivers is
      needed to characterize their mechanism and thereby allow for a more specific
      ablation strategy.

PMID- 16903958
TI  - Atrial fibrillation burden during the post-implant period after crt using device
      based diagnostics.
AB  - AF Burden After CRT Implantation. AIMS: Cardiac resynchronization therapy (CRT)
      is increasingly used in congestive heart failure (CHF) patients (with cardiac
      dyssynchrony). In addition to delivering therapy, CRT devices offer a variety of
      diagnostic tools for continuous long-term monitoring of clinically relevant
      information (i.e., occurrence and duration of arrhythmia episodes). METHODS AND
      RESULTS: Eighty-four patients with drug-refractory CHF in NYHA-class II-IV
      received a CRT device. The response to CRT was assessed by determining NYHA class
      at baseline and at 3 months follow-up. Atrial fibrillation (AF) burden (defined
      as time of AF per day) was continuously measured by the device. A significant
      gradual reduction of AF burden (from 9.88 +/- 12.61 to 4.20 +/- 9.24 [hours/day])
      and number of patients experiencing AF episodes (from 26 to 13) were observed
      during CRT. CONCLUSIONS: (1) Diagnostic features for long-term monitoring of
      physiological variables provide useful information on the state and course of AF
      and may improve disease management. (2) AF burden reduces over time during the
      first 3 months after CRT implantation.

PMID- 16903959
TI  - Electroanatomic characteristics of atrial premature beats triggering atrial
      fibrillation in patients with persistent versus paroxysmal atrial fibrillation.
AB  - APBs in Persistent Versus Paroxysmal AF. BACKGROUND: Although the electrical
      disconnection between the left atrium (LA) and pulmonary veins (PVs) by
      radiofrequency catheter ablation has been proven to be effective in controlling
      atrial fibrillation (AF), the recurrence rate is higher in patients with
      persistent AF (PeAF) than with paroxysmal AF (PAF). We hypothesized that the
      origin of the atrial premature beats (APBs) that trigger AF and the pattern of
      their breakthrough into the LA differ between PAF and PeAF. METHODS: We mapped 75
      APBs (53 APBs triggering AF, 22 isolated APBs) from the LA and PVs in 26 patients
      with AF (age: 49.5 +/- 9.6, males: 23, PAF = 17, PeAF = 9), using a noncontact
      endocardial mapping (NCM) system. The location of the preferential conduction
      (PC) sites and their conduction velocity (CV) were compared. RESULTS: In patients
      with PeAF, the earliest activation (EA) site and exit of the PC were more
      frequently located on the LA side of the LA-PV junction as compared with PAF (P <
      0.001). Eighty-one percent of the PCs were located in the area between the left
      and right superior PVs. The incidence of PCs was similar between the PeAF and PAF
      patients (P = NS). PCs were more commonly found with APBs inducing AF (63.3%)
      than with those not inducing AF (35.2%, P = 0.01). The CV of the PC was slower
      for PeAF than PAF (P < 0.001). The CV in the LA during sinus rhythm was also
      slower for PeAF than PAF (P < 0.01). CONCLUSION: PeAF was more frequently
      triggered by APBs from the LA side of the LA-PV junction than PAF and resulted in
      slower conduction than did PAF. These findings may help explain the higher
      potential for recurrence after electrical PV isolation in patients with PeAF.

PMID- 16903960
TI  - Incidence of atrial fibrillation in heart transplant patients: long-term follow
      up.
AB  - BACKGROUND: The incidence of atrial fibrillation (AF) in heart transplant
      patients has not been well documented. METHODS: To determine the incidence of AF
      in a cohort of patients undergoing cardiac transplantation, clinical data were
      obtained from a prospectively collected database for all consecutive orthotopic
      heart transplantation (OHT) patients and for all consecutive coronary artery
      bypass graft (CABG) surgery patients between January 1984 and March 2004 at our
      institution. A cohort of 1,714 OHT patients and low-risk CABG (normal ejection
      fraction [EF] and no left ventricular hypertrophy [LVH]) patients were age- and
      sex-matched. RESULTS: The average age in the two groups was 56 +/- 7 years with
      87% male and 81% white race and body mass index (BMI) of 26 +/- 4. There were 3
      cases of AF (0.3%) in the OHT group and 757 cases of AF (21%) in the low-risk
      CABG group. The strongest independent predictor of freedom from postoperative AF
      was having had a transplant (odds ratio [OR] 96, 95% confidence interval [CI] 13
      720). The incidence of AF, atrial flutter (AFL), and supraventricular tachycardia
      (SVT) in OHT was 0.33, 2.8%, and 1.3%, respectively. Given that incidence of AF,
      AFL, and SVT in historical post-CABG population is 25%, 17%, and 4.3%,
      transplanted patients appear to have lower incidence of AF, AFL, and SVT than the
      reference population. Consistent with this, transplanted patients underwent few
      ablation procedures for atrial arrhythmias. Additionally, the three patients with
      AF had bicaval anastomoses suggesting the possibility of PACs originating in the
      donor superior vena cava (SVC) or IVC (inferior vena cava) initiating AF in these
      patients. CONCLUSIONS: In a cohort study of transplant and low-risk CABG
      patients, the strongest independent predictor of freedom from AF is having
      undergone transplant surgery. One potential explanation for the markedly lower
      incidence of AF may be effective isolation of thoracic veins with documented
      cases retaining the native SVC.

PMID- 16903961
TI  - Cavotricuspid isthmus conduction is dependent on underlying anatomic bundle
      architecture: observations using a maximum voltage-guided ablation technique.
AB  - OBJECTIVES: We hypothesized an ablation strategy directly targeting muscle
      bundles might demonstrate functionally distinct "routes" of conduction,
      potentially shortening ablation times. BACKGROUND: Pathological study
      demonstrated that the cavotricuspid isthmus is composed of distinct anatomically
      defined bundles, many with intervening gaps of connective tissue. METHODS: A line
      was mapped in the "6 o'clock" region and bipolar electrogram amplitude measured
      during pullback. Zones of peak voltage were ablated first regardless of position.
      RF was delivered using either a 5-mm externally irrigated catheter, or an 8-mm
      nonirrigated catheter. The zone of largest remaining voltage was then
      sequentially targeted until conduction. RESULTS: Eighteen patients were recruited
      and followed for 7.9 +/- 1.9 months block occurred (mean age 64 +/- 11.6 years,
      male:female ratio 14:4). Bi-directional block was achieved in all patients with
      recurrence of atrial flutter in 1 patient. Mean total RF times was 4.7 +/- 2.8
      minutes with a mean of 6.1 +/- 3.3 applications, procedure time was 127.3 +/-
      37.7 minutes, and fluoroscopy time was 25.5 +/- 12.0 minutes. Two patterns of
      block were observed in the study group. Pattern A described no change in
      conduction times until block, observed in 6 (33%); pattern B described a stepwise
      block with discrete "jumps," observed in 12 (67%). CONCLUSIONS: An ablation
      strategy targeting high-voltage isthmus electrograms obviates the need for a
      complete anatomic line. This finding together with discrete "jumps" during
      ablation is consistent with the concept of conduction over discrete bundles
      rather than a diffuse sheet of muscle.

PMID- 16903962
TI  - Vein of Marshall activity during sustained atrial fibrillation.
AB  - BACKGROUND: The human vein of Marshall (VOM) activation patterns during sustained
      (persistent or permanent) atrial fibrillation (AF) have not been studied in
      detail. METHODS: VOM was cannulated via coronary sinus in six patients (67.3 +/-
      7.5 years old) having either persistent (N = 4) or permanent (N = 2) AF
      presenting for radiofrequency catheter ablation. RESULTS: At sinus rhythm in
      patients with persistent AF, there were frequent ectopic beats from the VOM as
      well as from left and right pulmonary veins (PVs). The ectopic activity
      originating from the VOM was highly fragmented. The P wave morphology associated
      with VOM ectopy was isoelectric in leads I and aVL, positive in leads II, III,
      aVF, and V2-V5, which is similar to the P wave morphology associated with left PV
      ectopic beats. During AF the activation cycle length at VOM was 140 +/- 31 msec,
      which was significantly shorter than that in other atrial sites (P < 0.05).
      Similarly, the dominant frequency at VOM (9.71 Hz +/- 1.52 Hz) was significantly
      higher than that at other atrial sites (P < 0.0001). In one patient, VOM ablation
      was associated with AF termination during radiofrequency energy application.
      CONCLUSIONS: Ectopic activity with complex local electrogram originating from VOM
      is commonly seen in patients with sustained AF. The P wave morphology associated
      with the ectopic beats from VOM and from the left PVs was similar. The rate of
      activation at VOM is significantly faster than other atrial and PV sites during
      AF. These findings show that rapid activation is present in the VOM during
      sustained AF in human patients.

PMID- 16903963
TI  - Characteristics of slow pathway conduction after successful AVNRT ablation.
AB  - BACKGROUND: AV node slow pathway conduction can persist following successful
      ablation for AV node reentrant tachycardia (AVNRT). We hypothesized that careful
      examination of AV nodal conduction curves before and after effective AVNRT
      ablation in patients with persistent slow pathway conduction could shed light on
      this apparent paradox. METHODS AND RESULTS: Thirty patients (age 40.9 +/- 14.3; 8
      male) were included. AV node function curves were created based on pre- and
      postablation atrial extrastimulus testing. Analysis of slow pathway function
      curves demonstrated significant decrease in AH for any given coupling interval
      after ablation (mean difference -68.1 [-94.5, -41.7] P < 0.001), graphically
      indicated by downward displacement of the curve. In addition, mean slow pathway
      effective refractory period (ERP) increased from 247.9 +/- 36.1 msec to 288.6 +/-
      56.0 msec (P < 0.001); mean maximum AH interval decreased from 361.3 +/- 114.2
      msec to 306.9 +/- 65.2 msec (P = 0.013); mean difference in minimum and maximum
      AH interval during slow pathway conduction decreased (from 94.5 +/- 75.8 msec to
      59.6 +/- 46.2 msec (P = 0.016). Finally, mean difference between the fast and
      slow pathway effective refractory periods, the span of coupling intervals over
      which slow pathway conduction occurred, decreased (from 113.9 +/- 61.4 msec to
      63.2 +/- 41.5 msec, P = 0.001). CONCLUSIONS: Ablation, which successfully
      eliminates inducible and spontaneous AVNRT in the presence of persistent slow
      pathway conduction, is associated with significantly altered slow pathway
      conduction characteristics, indicating the presence of a damaged or different
      slow pathway after ablation, incapable of sustaining tachycardia.

PMID- 16903964
TI  - Clinical experience with tiered atrial therapies and atrial arrhythmia prevention
      algorithms in a dual chamber cardioverter defibrillator.
AB  - INTRODUCTION: The acceptance of atrial arrhythmia features in implantable
      cardioverter defibrillators (ICDs) will depend on their ability to appropriately
      discriminate atrial tachyarrhythmias/atrial fibrillation (AT/AF). This study
      tested the effectiveness of an atrial/ventricular ICD with advanced atrial
      detection and new algorithms designed to prevent atrial arrhythmias. METHODS AND
      RESULTS: Ninety-five patients were implanted with a dual chamber ICD (Model 1900,
      Guidant Corporation, MN, USA) at 25 US centers. Ten patients received a coronary
      sinus (CS) lead allowing a defibrillation vector for AT/AF cardioversion. Follow
      up was 12.2 months. The addition of new atrial features designed for detection,
      discrimination, and prevention of AT/AF had no adverse effect upon detection of
      induced ventricular fibrillation (VF) (mean detection time with new features ON
      was 2.22 seconds vs 2.19 seconds with features OFF). A total of 100% of the
      induced and spontaneous ventricular and atrial arrhythmias receiving shock
      therapy were reviewed as appropriate detection. Atrial shock conversion efficacy
      for spontaneous and induced AT/AF episodes was 83% and 96%, respectively (144
      spontaneous, 162 induced episodes). A 3-month randomized crossover trial of
      atrial preventative pacing features did not result in adverse effects, but there
      was no clinical efficacy for prevention of AT/AF. CONCLUSION: Enhanced atrial
      detection and discrimination features combined with tiered atrial therapies did
      not adversely impact the ability of the ICD (Model 1900) to appropriately detect
      and treat ventricular tachyarrhythmias.

PMID- 16903965
TI  - Evaluation of exercise-induced T wave changes in patients with idiopathic dilated
      cardiomyopathy before and after beta-blocker therapy.
AB  - INTRODUCTION: Ventricular repolarization abnormalities are thought to contribute
      to lethal ventricular arrhythmias in patients with idiopathic dilated
      cardiomyopathy (DCM). The purpose of this study was to evaluate exercise-induced
      T wave changes in DCM patients before and after beta-blocker therapy to
      investigate repolarization abnormalities. METHODS AND RESULTS: Treadmill exercise
      testing was performed in 20 DCM patients and 50 normal subjects. T wave amplitude
      (TA: baseline to T wave apex; mV) and recovery time (RT: QRS onset to the maximum
      dV/dt point of the T wave; msec) were measured before and 1 minute after peak
      exercise. TA was averaged in the right and left precordial leads (TA(V1-3), TA(V4
      6)). RT was normalized to the maximum QT interval in the 12-lead ECG and
      expressed as the %RT (%RT). %RT was also averaged in the precordial leads (%RT(V1
      3), %RT(V4-6)). After exercise, TA increased and %RT decreased in both groups. In
      DCM patients, TA(V1-3) was greater and TA(V4-6) was less than in normal subjects
      before and after exercise. There was no difference in %RT(V1-3) between the
      groups, but %RT(V4-6) was greater in DCM patients both before and after exercise.
      DCM patients repeated the same evaluation after 6 months of oral beta-blocker
      therapy. Compared with measurements before beta-blocker therapy, TA(V1-3) and
      %RT(V1-3) did not change. However, TA(V4-6) increased and %RT(V4-6) decreased
      significantly both before and after exercise. CONCLUSION: DCM patients showed
      small TA and large %RT in the left precordial leads at rest as well as after
      exercise. Chronic beta-blocker therapy in DCM patients normalized these
      ventricular repolarization abnormalities.

PMID- 16903966
TI  - Heart rate turbulence as a noninvasive risk predictor of ventricular
      tachyarrhythmias in myotonic dystrophy type 1.
AB  - INTRODUCTION: Myotonic dystrophy type 1 (MD1) is the most common muscular
      dystrophy of adult life. Cardiac involvement is characterized by disorders of
      atrioventricular conduction, ventricular arrhythmias, and sudden death. Heart
      rate turbulence (HRT) is a noninvasive risk predictor in patients affected by
      ischemic heart disease. The aim of our study is to assess the prognostic value of
      HRT in MD1 patients. METHODS AND RESULTS: We performed HRT analysis by 24-hour
      Holter recording to calculate turbulence onset (TO) and turbulence slope (TS) in
      29 MD1 patients (mean age 52 +/- 10 years), and in 30 patients (mean age 52 +/-
      13 years) with frequent ventricular arrhythmias and structurally normal heart
      (VANH). An electrophysiological study (EPS) tested ventricular arrhythmias
      inducibility in 22 MD1 patients. TO was significantly different between MD1 and
      VANH patients (-1.66 +/- 2.04 and -2.98 +/- 1.79%, respectively, P 0.01), while
      no difference was observed in TS between MD1 and VANH patients (11.12 +/- 6.46
      and 9.12 +/- 6 msec/beat, respectively). On EPS, sustained ventricular
      arrhythmias (SVA) were induced in six MD1 patients. TO was significantly
      different in inducible MD1 patients (0.88 +/- 1.95%), as compared with both
      noninducible (-2.49 +/- 1.43%, P < 0.001) or no eligible to EPS (-1.93 +/- 1.63%,
      P < 0.005) MD1 patients and to VANH patients (-2.98 +/- 1.79%, P < 0.001).
      CONCLUSIONS: An impairment of TO, a measure of HRT, suggesting impaired cardiac
      parasympathetic activity, may be a useful, noninvasive predictor of arrhythmic
      risk in MD1 patients.

PMID- 16903967
TI  - Effects of single-site versus biventricular epicardial pacing on myocardial
      performance in an immature animal model of atrioventricular block.
AB  - INTRODUCTION: Single-site ventricular pacing results in dyssynchronous
      ventricular activation and may contribute to ventricular dysfunction. We
      evaluated epicardial biventricular (BiV) pacing as a means of maintaining
      synchronous ventricular activation in an acute piglet model of AV block with
      normal ventricular anatomy and function. METHODS AND RESULTS: We used left
      ventricular (LV) impedance catheters and tissue Doppler imaging to assess the
      cardiodynamics of immature piglets (n = 6, 33-78 days, 9.35 +/- 0.85 kg).
      Following catheter ablation of the AV node, a pacemaker was programmed 20 beats
      per minute above the intrinsic atrial rate. The animals were paced at 5-minute
      intervals via the following AV sequential configurations: Right atrial appendage
      (RA)-RV apex (RVA), RA-LV apex (LVA), and RA-biventricular (RVA/LVA). RA-RVA was
      the experimental control. LV systolic mechanics, measured by the slope of the end
      systolic pressure-volume relationship (E(es)), increased with BiV pacing (12.8 +/
      3.4 mmHg/mL, P < 0.02) or single-site LVA pacing (10.6 +/- 3.4 mmHg/mL, P <
      0.05) compared with single-site RVA pacing (8.3 +/- 1.4 mmHg/mL). QRS duration
      lengthened compared with sinus rhythm (42 +/- 8 msec) with either RVA (56 +/- 9
      msec, P < 0.02) or LVA (54 +/- 7 msec, P < 0.03), but not with BiV (48 +/- 7
      msec, P = 0.08) pacing. Tissue Doppler imaging showed LV dyssynchrony with RVA
      (septal-to-lateral delay 46.0 +/- 51.7 msec), with return toward normal with LVA
      (-9.6 +/- 33.6 msec, P < 0.04) or BiV (-4.1 +/- 33.8 msec, P < 0.04) pacing.
      CONCLUSIONS: In this acute immature piglet model of AV block, LV performance
      improved with single-site pacing from the LVA and BiV pacing (RVA/LVA), as
      compared with single-site pacing from the RVA. These changes correlated with
      tissue Doppler indices of mechanical synchrony, though not necessarily with QRS
      duration.

PMID- 16903968
TI  - Video-assisted thoracoscopy to treat atrial tachycardia arising from left atrial
      appendage.
AB  - A 17-year-old male with tachycardia-induced cardiomyopathy presented with
      persistent, drug-resistant atrial tachycardia (AT). An electrophysiological study
      suggested focal abnormal automaticity, and localized the AT origin to the left
      atrial appendage. Radiofrequency catheter ablation at the site of the earliest
      endocardial activation during AT failed. A minimally invasive, video-assisted
      thoracoscopic (VAT) atrial appendectomy terminated the AT and restored left
      ventricular contractility. The patient remained free of AT and normal left
      ventricular function was maintained over a 24-month follow-up period. To our
      knowledge, we are the first to use VAT atrial appendectomy to treat focal AT.

PMID- 16903969
TI  - Postero-lateral scar tissue resulting in non-response to cardiac
      resynchronization therapy.
AB  - In large cardiac resynchronization therapy (CRT) trials, approximately 20-30% of
      patients did not respond to CRT. Recent studies indicated that left ventricular
      (LV) dyssynchrony is needed for response to CRT. However, the presence of LV
      dyssynchrony may not be the only determinant of response, because some patients
      with LV dyssynchrony do not benefit from CRT. In the current case report, we
      present a patient with ischemic cardiomyopathy, NYHA class III heart failure
      symptoms, and substantial LV dyssynchrony on tissue Doppler imaging who underwent
      CRT implantation but did not respond. Following CRT, LV dyssynchrony was not
      reduced and the patient did not improve in clinical symptoms or LV function. The
      lack of LV resynchronization was explained by the presence of extensive scar
      tissue in the region of the tip of the LV pacing lead resulting in ineffective LV
      pacing. In patients with ischemic cardiomyopathy and history of previous
      infarction, assessment of scar tissue should be considered before CRT
      implantation.

PMID- 16903970
TI  - An unusual form of bundle branch reentrant tachycardia.
AB  - INTRODUCTION: We report the case of a 36-year-old patient with a longstanding
      history of paroxysmal tachycardia. METHODS AND RESULTS: During the
      electrophysiological study, the H-V interval was prolonged in sinus rhythm, and a
      second potential (H'') with distal to proximal activation pattern was recorded in
      the region of the proximal His-Purkinje system. Two wide QRS complex tachycardias
      were induced, both with V-A dissociation. One application of radiofrequency
      energy at the site with earliest and largest H'' potential during sinus rhythm
      cured both tachycardias. The right and left bundle branch block morphology
      tachycardias were diagnosed as clockwise and counterclockwise bundle branch
      reentrant tachycardia. The H'' potential represented the retrograde right bundle
      potential during sinus rhythm and bundle branch block reentrant tachycardia.

PMID- 16903971
TI  - Atrial tachycardia originating from the upper left atrial septum: demonstration
      of transseptal interatrial conduction using the infolded atrial walls.
AB  - We report a rare case of atrial tachycardia (AT) originating from the upper left
      atrial septum. Electroanatomic mapping of both atria demonstrated that the
      earliest atrial activation during AT occurred at the upper left atrial septum 26
      msec before the onset of the P wave, followed by the mid-right atrial septum (10
      msec before the onset of the P wave) and then the upper right atrial septum just
      adjacent to the left septal AT site (1 msec before the onset of the P wave),
      indicating detour pathway conduction from the upper left to the upper right
      atrium. Embryologically, it was suggested that the superior components of the
      secondary atrial septum are made by the infolded atrial walls and could develop a
      transseptal detour pathway involving the left-side atrial septal musculature, the
      superior rim of the oval fossa and the right-side atrial septal musculature. A
      single radiofrequency application targeting the upper left atrial septum
      successfully abolished the AT.

PMID- 16903972
TI  - Wide and narrow QRS complex tachycardia: what is the mechanism?

PMID- 16903973
TI  - Reversal of left atrial-pulmonary vein remodeling in hypertensive heart disease.

PMID- 16903974
TI  - Images in electrophysiology: latent pacemaker infection.

PMID- 16903975
TI  - Augmentation of pulsus alternans by a prematureventricular beat.

PMID- 16903977
TI  - Plasma lipid concentrations after 1.5 years of exposure to nevirapine or
      efavirenz together with stavudine and lamivudine.
AB  - OBJECTIVES: To assess long-term changes in lipids and lipoproteins concentrations
      associated with exposure to non-nucleoside reverse transcriptase inhibitors.
      METHODS: Long-term analysis of plasma lipid concentrations was performed in
      patients starting first-line antiretroviral therapy with stavudine (d4T) and
      lamivudine, and either nevirapine or efavirenz. RESULTS: Concentrations of total
      cholesterol, low-density lipoprotein cholesterol and triglycerides continued to
      increase, while high-density lipoprotein cholesterol showed a slight decrease
      compared with earlier reported increases after 48 weeks. CONCLUSIONS: Changes in
      body fat distribution expected to occur with continued exposure to d4T could
      offer a potential explanation for these findings.

PMID- 16903978
TI  - The value of serum albumin in pretreatment assessment and monitoring of therapy
      in HIV/AIDS patients.
AB  - OBJECTIVES: We sought to examine the utility of serum albumin measurement in
      staging AIDS and monitoring patients' response to therapy. METHODS: The possible
      importance of serum albumin measurement in assessing AIDS stage and in monitoring
      the response to highly active antiretroviral therapy using CD4 cell count and
      body weight as parameters was examined in 185 consecutive HIV-infected, therapy
      naive individuals who were recruited for antiretroviral therapy at the university
      of Ilorin Teaching Hospital. The regimen included lamivudine, stavudine and
      nevirapine. The diagnosis of AIDS was established through a combination of
      clinical features and HIV seropositivity using two different enzyme-linked
      immunosorbent assay techniques. Serum albumin level was determined by the
      Bromocresol green method, while the CD4 lymphocyte count was obtained using the
      Dynal T4 count method. Body weight was measured in kilograms with light clothes
      on. RESULTS: There were significant positive correlations between pretreatment
      albumin and both pretreatment CD4 cell count and pretreatment weight, and between
      post-treatment albumin and both post-treatment weight and post-treatment CD4 cell
      count up to a count of 700 cells/microL. There were also significant positive
      correlations between increase in serum albumin and both increase in body weight
      and duration of treatment. CONCLUSIONS: We conclude that, in developing countries
      where many patients may not be able to afford to pay for CD4 cell counts and
      viral load tests, which are the traditional markers for HIV disease, serum
      albumin would be a very useful surrogate test for predicting severity of HIV
      infection and for clinical monitoring of response to antiretroviral therapy.

PMID- 16903979
TI  - Influence of a monocyte chemoattractant protein 1 mutated allele on the response
      to protease inhibitor-based antiretroviral therapy.
AB  - BACKGROUND: Antiretroviral drug efficacy has been widely studied in relation to
      viral factors. Mutations in the HIV co-receptors and their natural chemokines,
      however, may be critical in HIV infection and treatment response. We compared the
      efficacy of protease inhibitor (PI) treatment among PI-naive patients grouped
      according to whether they carried the chemokine CC motif receptor 2 (CCR-2) 64I
      and monocyte chemoattractant protein 1 (MCP-1)-2518G alleles. METHODS AND
      RESULTS: HIV-infected patients who were PI-naive were selected for the study
      (n=164) but there was no restriction on lymphocyte CD4 count or plasma HIV viral
      load. Follow-up was for the first 24 months of treatment. Clinical and laboratory
      data were obtained every 3 months. All the participants were genotyped for the
      MCP-1-2518G, CCR-2 64I, CCR-5Delta32 and stromal derived factor 1 (SDF1) 3'A
      mutated alleles. The results indicated that patients carrying the mutated allele
      of MCP-1 had a higher mean CD4 cell count throughout the follow-up period than
      those with the common allele (P=0.01). Also, patients with the MCP-1 and CCR-2
      mutated alleles were more likely to continue to have an undetectable viral load
      following treatment (P=0.05). CONCLUSION: A better response to PI treatment
      appears to be conferred by mutations in the host MCP-1 and CCR-2 genes, and may
      be related to the cellular axis-of-entry used by the retrovirus.

PMID- 16903980
TI  - Community-onset methicillin-resistant Staphylococcus aureus in an urban HIV
      clinic.
AB  - OBJECTIVES: To determine the proportion of skin/soft tissue infections (SSTIs)
      and to determine risks for MRSA infection caused by methicillin-resistant
      Staphylococcus aureus (MRSA) in HIV-infected out-patients. METHODS: We conducted
      a prospective study of SSTIs in HIV-infected out-patients. A questionnaire was
      used to record MRSA risk factors and treatment. In vitro testing for antibiotic
      susceptibility, inducible clindamycin resistance, panton-valentine leucocidin
      (PVL) toxin, and the staphylococcal chromosomal cassette mec (SCCmec) type was
      performed using standardized methods. Treatment outcomes included resolution of
      primary site of infection, nonresolution of infection and reinfection and were
      confirmed at clinic visit and/or telephone follow-up. RESULTS: Forty-one of 44
      patients had an SSTI caused by MRSA. African-Americans comprised 21 of 41 MRSA
      patients. The median CD4 count of MRSA patients was 411 cells/microL. Four
      patients required hospitalization and three patients had secondary bacteraemia.
      Twenty-one of 41 MRSA patients had healthcare-associated (HCA) MRSA risk factors
      including a history of prior MRSA infection (n=9) and hospitalization within 6
      months (n=11). Other prevalent MRSA risk factors included receipt of systemic
      antibiotics within 6 months (n=21) and previous incarceration (n=19). Twenty-two
      patients had a significant non-HIV-related comorbid illness. The majority of
      isolates were susceptible to trimethoprim-sulfamethoxazole, tetracycline, and
      clindamycin. Inducible clindamycin resistance was detected in 0 of 16
      erythromycin-resistant, clindamycin-susceptible MRSA isolates. Twenty-one of 24
      isolates tested positive for SCCmec type IV. Twenty-four of 24 isolates tested
      positive for the PVL gene. Antibiotic treatment was discordant (bacteria
      nonsusceptible to antibiotic used) in eight MRSA patients. The primary SSTI
      resolved in 37 of 40 MRSA patients. Recurrence of infection at a site other than
      the primary site was relatively common (11 patients). CONCLUSIONS: We found a
      high rate of MRSA causing SSTI in community-dwelling patients. The majority of
      isolates were positive for PVL and SCCmec IV, which is typical of community
      associated MRSA isolates causing SSTIs in the general population. Inducible
      clindamycin resistance was not detected. Most patients had MRSA risk factors. The
      initial site of infection resolved in most cases but subsequent MRSA infection
      was relatively common.

PMID- 16903981
TI  - The impact of highly active antiretroviral therapy on the incidence and outcomes
      of AIDS-defining cancers in Southern Alberta.
AB  - OBJECTIVES: To determine the impact of highly active antiretroviral therapy
      (HAART) on the incidence and outcomes of Kaposi's sarcoma (KS), non-Hodgkin's
      lymphoma (NHL) and invasive cervical cancer/dysplasia in a well-defined
      geographical HIV-infected population between 1984 and 2005. METHODS: A clinic
      database search, chart review and verification with public health records were
      undertaken for all AIDS-defining cancers diagnosed in Southern Alberta before and
      after the introduction of HAART. RESULTS: A total of 2,137 patients with 9,265
      person-years of HIV follow-up care were reviewed. One hundred and forty-three
      cases of KS, 64 cases of NHL and 11 cases of invasive cervical cancer/dysplasia
      were identified. KS and NHL together accounted for 15% of clinical presentations
      with an AIDS-defining illness that led to the HIV diagnosis. Following the
      introduction of HAART, the reduced number of severely immunocompromised patients
      was associated with 92 and 84% reductions in new diagnoses of KS and NHL,
      respectively, which were seen mainly in clinic patients declining or failing
      HAART. Crude reductions of 94 and 65% in mortality from KS and NHL, respectively,
      were also seen. The prevalences of KS, NHL and invasive cervical cancer/dysplasia
      have recently stabilized at 3, 1 and 5% of the population, respectively.
      CONCLUSIONS: The introduction of HAART has dramatically reduced the incidence of
      KS and NHL and improved survival from these cancers for most patients in HIV
      care. However, patients still present with KS and NHL leading to their HIV
      diagnosis.

PMID- 16903982
TI  - Incidence and risk factors of rash associated with efavirenz in HIV-infected
      patients with preceding nevirapine-associated rash.
AB  - OBJECTIVE: To determine the incidence and risk factors of rash associated with
      efavirenz in HIV-infected patients with preceding nevirapine-associated rash.
      METHODS: A retrospective cohort study was conducted in HIV-infected patients
      diagnosed with nevirapine-associated rash who subsequently received efavirenz
      between July 2003 and January 2005. Patients were followed up for 3 months after
      receiving efavirenz. Possible risk factors, including demographics, previous
      opportunistic infections, CD4 cell count, viral load, severity of nevirapine
      associated rash and concurrent drugs, were studied and compared between those who
      had (group A) and did not have (group B) rash associated with efavirenz. RESULTS:
      A total of 122 patients (52.5% male) were included in the study, with a mean age
      of 38.2 years. Median (and interquartile range) CD4 cell count and viral load
      were 55 (20-167) cells/microL and 86,150 (35,321-700,750) HIV-1 RNA copies/mL,
      respectively. Of the 122 patients, 10 (8.2%) developed rash associated with
      efavirenz and all required discontinuation of efavirenz. The baseline
      characteristics of group A (10 patients) and group B (112 patients) were similar.
      Median (and interquartile range) time from nevirapine discontinuation to
      efavirenz initiation was 12 (9-21) days in group A and 11 (7-21) days in group B
      (P=0.765). None of the risk factors investigated was associated with developing
      rash associated with efavirenz. The preceding development of severe nevirapine
      associated rash had a trend towards a higher rate in group A than in group B
      (20.0% vs 10.7%; odds ratio=2.08; 95% confidence interval 0.39-10.97; P=0.322).
      CONCLUSIONS: The majority (>90%) of HIV-infected patients with CD4 counts <200
      cells/muL who had preceding nevirapine-associated rash could tolerate efavirenz
      well. Efavirenz may be an option for subsequent use in these patients,
      particularly in those who had preceding nevirapine-associated rash.

PMID- 16903983
TI  - CD4 percentage is an independent predictor of survival in patients starting
      antiretroviral therapy with absolute CD4 cell counts between 200 and 350
      cells/microL.
AB  - OBJECTIVE: To determine the prognostic value of baseline CD4 percentage in terms
      of patient survival in comparison to absolute CD4 cell counts for HIV-positive
      patients initiating highly active antiretroviral therapy (HAART). METHODS: A
      population-based cohort study of 1,623 antiretroviral therapy-naive HIV-positive
      individuals who initiated HAART between 1 August 1996 and 30 June 2002 was
      conducted. Cumulative mortality rates were estimated using Kaplan-Meier methods.
      Cox proportional hazards regression was used to model the effect of baseline CD4
      strata and CD4 percentage strata and other prognostic variables on survival. A
      subgroup analysis was conducted on 417 AIDS-free subjects with baseline CD4
      counts between 200 and 350 cells/microL. RESULTS: In multivariate models, low CD4
      percentages were associated with increased risk of death [CD4%<5, relative hazard
      (RH)=4.46; CD4% 5-14, RH=2.43; P<0.01 for both] when compared with those subjects
      with an initial CD4 fraction of 15% or greater, but had less predictive value
      than absolute CD4 counts. In subgroup analyses where absolute CD4 strata were not
      associated with mortality, a baseline CD4 fraction below 15% [RH=2.71; 95%
      confidence interval (CI) 1.20-6.10], poor adherence to therapy and baseline viral
      load >100,000 HIV-1 RNA copies/mL were associated with an increased risk of
      death. CONCLUSION: CD4 percentages below 15% are independent predictors of
      mortality in AIDS-free patients starting HAART, including those with CD4 counts
      between 200 and 350 cells/microL. CD4 percentage should be considered for
      inclusion in guidelines used to determine when to start therapy.

PMID- 16903985
TI  - A randomized, open-label study to compare the effects of two different doses of
      recombinant human growth hormone on fat reduction and fasting metabolic
      parameters in HIV-1-infected patients with lipodystrophy.
AB  - BACKGROUND: Several studies have shown beneficial effects of recombinant human
      growth hormone (r-hGH) in reducing visceral adipose tissue (VAT) in HIV-1
      infected patients with lipodystrophy. METHODS: Patients were randomized to r-hGH
      4 mg daily (group A) or three times per week (group B) over 12 weeks, followed by
      a 2 mg daily maintenance dose for 12 weeks. Magnetic resonance imaging (MRI)
      scans were performed to assess body composition. RESULTS: A total of 26 subjects
      were included in the study. VAT was reduced overall by 35.1 cm(2) (29.5%) at week
      12 and by 49 cm(2) (39.9%) at week 24, respectively, compared with baseline
      (P<0.001 for both comparisons). By week 12, VAT was reduced by 27 and 29% (A vs
      B; P=0.47) while facial fat was reduced by 3.3 and 2.6 cm(2) in groups A and B,
      respectively (P=0.96). Over 24 weeks, VAT was reduced by 42 and 38% (P=0.35) and
      facial fat by 3.2 and 2.4 cm(2) in groups A and B, respectively (P=0.91),
      compared with baseline. There was a greater increase in high-density lipoprotein
      (HDL) in group A than in group B (4.9 vs 2.4 mg/dL in week 12 and 7.1 vs -0.4
      mg/dL in week 24; P=0.03). Fasting insulin levels increased, whereas glucose and
      insulin measured in oral glucose tolerance tests remained unchanged. Drug-related
      side effects were transient and reversible, but more common in group A (67%) than
      in group B (29%). CONCLUSIONS: This study confirms reports that r-hGH effectively
      reduces VAT, with a relatively small reduction of facial and limb fat.

PMID- 16903984
TI  - Abnormal glucose metabolism among older men with or at risk of HIV infection.
AB  - OBJECTIVES: To determine factors associated with diabetes, insulin resistance,
      and abnormal glucose tolerance in older men with or at risk of HIV infection.
      METHODS: Diabetes was assessed by self-report in 643 men >or=49 years old with or
      at risk of HIV infection. In a subset of 216 men without previously diagnosed
      diabetes [including 90 HIV-uninfected men, 28 HIV-infected, antiretroviral-naive
      men, 28 HIV-infected men taking non-protease inhibitor (PI)-containing highly
      active antiretroviral therapy (HAART), and 70 HIV-infected men taking PI
      containing HAART], an oral glucose tolerance test with insulin levels was
      performed. HIV serology, CD4 cell count, weight, height and waist circumference
      were measured. Antiretroviral use, drug use, family history of diabetes, physical
      activity and sociodemographic data were obtained using standardized interviews.
      RESULTS: Of 643 participants, 116 (18%) had previously diagnosed diabetes. With
      the oral glucose tolerance test, 15 of 216 men (7%) were found to have
      undiagnosed diabetes and 40 (18%) impaired glucose tolerance. Factors
      independently associated with previously diagnosed diabetes included use of non
      PI-containing HAART, methadone treatment, positive CAGE test for alcoholism,
      obesity and family history of diabetes. Factors independently associated with
      greater insulin resistance included waist circumference and heroin use. Factors
      independently associated with abnormal glucose tolerance (impaired glucose
      tolerance or diabetes) included age >or=55 years and Hispanic ethnicity.
      CONCLUSIONS: HIV-infected men with diabetes risk factors should undergo screening
      for diabetes regardless of HAART use. Interventions targeting modifiable risk
      factors, including overweight and physical inactivity, are warranted. The
      potential impact of opiate and alcohol abuse on glucose metabolism should be
      recognized in clinical care, and addressed in future research studies of HIV
      infected persons.

PMID- 16903986
TI  - Prevalence of risk factors for cardiovascular disease in HIV-infected patients
      over time: the Swiss HIV Cohort Study.
AB  - OBJECTIVE: Metabolic changes caused by antiretroviral therapy (ART) may increase
      the risk of coronary heart disease (CHD). We evaluated changes in the prevalence
      of cardiovascular risk factors (CVRFs) and 10-year risk of CHD in a large cohort
      of HIV-infected individuals. METHODS: All individuals from the Swiss HIV Cohort
      Study (SHCS) who completed at least one CVRF questionnaire and for whom
      laboratory data were available for the period February 2000 to February 2006 were
      included in the analysis. The presence of a risk factor was determined using cut
      offs based on the guidelines of the National Cholesterol Education Program (NCEP
      ATP III), the Joint National Committee on Prevention, Detection, Evaluation, and
      Treatment of High Blood Pressure (JNC7), the American Diabetes Association, and
      the Swiss Society for Cardiology. RESULTS: Overall, 8,033 individuals completed
      at least one CVRF questionnaire. The most common CVRFs in the first completed
      questionnaire were smoking (57.0%), low high-density lipoprotein (HDL)
      cholesterol (37.2%), high triglycerides (35.7%), and high blood pressure (26.1%).
      In total, 2.7 and 13.8% of patients were categorized as being at high (>20%) and
      moderate (10-20%) 10-year risk for CHD, respectively. Over 6 years the percentage
      of smokers decreased from 61.4 to 47.6% and the percentage of individuals with
      total cholesterol >6.2 mmol/L decreased from 21.1 to 12.3%. The prevalence of
      CVRFs and CHD risk was higher in patients currently on ART than in either
      pretreated or ART-naive patients. CONCLUSION: During the 6-year observation
      period, the prevalence of CVRFs remains high in the SHCS. Time trends indicate a
      decrease in the percentage of smokers and individuals with high cholesterol.

PMID- 16903987
TI  - Lymphoid pneumonitis as an immune reconstitution inflammatory syndrome in a
      patient with CD4 cell recovery after HAART initiation.
AB  - In the era of highly active antiretroviral therapy (HAART), immune reconstitution
      inflammatory syndrome (IRIS) has come to present a significant clinical
      challenge. Following the recovery of memory T cells, latent infections may lead
      to clinical and laboratory deterioration despite immunological and virological
      reconvalescence. However, many other forms of complications after induction of
      HAART, which are not entirely understood, must be included in the entity of IRIS.
      Here we report a case of a patient complaining of respiratory distress and fever
      10 days after initiating HAART. Radiologically and clinically, his findings
      mimicked Pneumocystis jiroveci pneumonia. However, no infectious agent could be
      detected, and bronchoalveolary lavage showed a high cell count (90% lymphocytes
      and 4% eosinophils) consistent with interstitial pneumonitis. He improved
      dramatically after treatment with oral steroids.

PMID- 16903988
TI  - Fulminant toxoplasmosis causing fatal pneumonitis and myocarditis.
AB  - The obligate intracellular protozoa Toxoplasma gondii is a serious cause of
      morbidity and mortality in patients with AIDS. Toxoplasmosis most frequently
      manifests as life-threatening encephalitis, although extracerebral sites may be
      involved with or without toxoplasmic encephalitis. Consequently, toxoplasmosis
      can present in an unusual manner, and may not be included in the differential
      diagnosis in the absence of encephalitic symptoms. There are few reports of
      fulminant toxoplasmic myocarditis resulting in death. Toxoplasmic pneumonitis is
      responsible for less than 1% of HIV-related pulmonary complications, and can
      occasionally cause fatal septic shock. Two such clinicopathological presentations
      of toxoplasmosis are reported here. One patient presented with cardiorespiratory
      signs and symptoms, whilst the second patient presented with pneumonitis and
      renal failure. Neither patient was initially known to be HIV-infected, nor did
      they have clinical symptoms indicating toxoplasmic encephalitis. Toxoplasmosis
      was only diagnosed on autopsy and had resulted in death by causing a fulminant
      myocarditis and a pneumonitis. As overwhelming toxoplasmosis infection may prove
      rapidly fatal, these two case reports serve as a clinical reminder to consider
      toxoplasmosis in the differential diagnosis of HIV-infected patients who present
      with severe cardiorespiratory signs and symptoms. Furthermore, the cases
      emphasize the potential importance of early tissue biopsy in patients presenting
      with immunosuppression-associated organ failure, and show the importance of
      requesting a postmortem examination if the cause of death cannot be ascertained
      in vivo.

PMID- 16903989
TI  - Are Australians able to access new medicines on the pharmaceutical benefits
      scheme in a more or less timely manner? An analysis of pharmaceutical benefits
      advisory committee recommendations, 1999-2003.
AB  - OBJECTIVE: Timely access to necessary medicines that Australians need is one of
      the four pillars of the Australian Government's National Medicines Policy. We
      were interested to determine whether there was a change in the time taken for
      medicines to be listed once recommended by the Pharmaceutical Benefits Advisory
      Committee (PBAC). METHODS: Descriptive statistics were used to show the pattern
      of recommendations for PBAC meetings from 1999 to 2003. For successful
      recommendations, we developed a linear regression model to analyze the time to
      list from the PBAC meeting to date of listing (time to list). The model
      determined whether this time had changed over the 4-year period, and the reasons
      for any changes. RESULTS: The PBAC made 307 positive recommendations at its 17
      meetings over the study period. Ninety percent resulted in a Pharmaceutical
      Benefits Scheme (PBS) listing on or before April 1, 2005. Eighty-two percent of
      the recommendations made in 1999 and 2000 resulted in early or on-time listings.
      In 2001, 2002, and 2003, the comparable proportions were 67%, 68%, and 75%. Mean
      times to list for the years from 1999 to 2003 were similar (approximately 23
      weeks), except in 2001 where it was 30 weeks. CONCLUSIONS: Over the study period,
      90% of all PBAC recommendations resulted in a PBS listing. In 2001 there was a
      statistically significant increase in the mean time to list. In addition, it
      appears that recommendations for new listings and new indications (medicines that
      are likely to result in substantial Government expenditure) were associated with
      a longer time to list.

PMID- 16903990
TI  - Trends in the measurement of health utilities in published cost-utility analyses.
AB  - OBJECTIVE: The Panel on Cost-Effectiveness in Health and Medicine recommended the
      compilation of a catalog of health state utility weights for use in cost-utility
      analyses (CUAs), and has given methodological recommendations. This study
      presents an update, through 2001, to our current registry of utility weights
      (available at http://www.tufts-nemc.org/cearegistry; previously at
      http://www.hsph.harvard.edu/cearegistry), and documents recent changes in methods
      used for utility weight elicitation. METHODS: We searched the English-language
      medical literature for original CUAs reporting outcomes as cost per quality
      adjusted life-year (QALY). Two trained readers independently audited each
      article, abstracting data on the health state descriptions, corresponding utility
      weights, methods of elicitation, and sources of the estimates. The utility
      elicitation methods from 1998 to 2001 were compared with the methods used to
      obtain utilities before 1998. RESULTS: We identified 306 CUAs published after
      1998, reporting 1210 separate health-related utility estimates, bringing the
      total in our catalog to 2159 weights. Most frequently, health states pertained to
      the circulatory system and oncology. Methods varied substantially: 36% of authors
      used direct elicitation (standard gamble, time trade-off or rating scale), 23%
      used generic health status instruments (EQ-5D, Health Utilities Index, etc.), and
      25% estimated weights based on clinical judgment. Community preferences were used
      in 27% of the values. Compared with pre-1998, utilities published from 1998 to
      2001 were more likely to be elicited using a generic instrument, more likely
      elicited from community samples, and less likely derived from expert opinion,
      with no formally employed methodology. CONCLUSIONS: Increasingly, analysts
      conducting CUAs are using generic, preference-weighted instruments, and relying
      on community-based preferences. Our catalog of utility weights provides a useful
      reference tool for producers and consumers of CUAs, but also highlights the
      continued need for improvement in methods and transparency.

PMID- 16903991
TI  - An economic evaluation of two ototopical treatments for acute otitis media in
      tympanostomy tube patients.
AB  - OBJECTIVE: The goal of this research was to determine the cost-effectiveness of
      ciprofloxacin 0.3%/dexamethasone 0.1% (CD) otic suspension versus ofloxacin 0.3%
      otic solution (OFX) for treatment of acute otitis media in tympanostomy tube
      patients. METHODS: A decision-analytic model was used to emulate the ototopical
      treatment of acute otitis media in patients with tympanostomy tubes. The economic
      outcome was the cost per otorrhea-free day (OFD) achieved per episode of care.
      Three tiers of antimicrobial therapy were modeled, with each successive tier
      representing the retreatment of clinical failures from the preceding tier. First
      tier therapy compared CD and OFX using outcome measures obtained from a
      randomized clinical trial (n = 599). Second-tier therapy modeled the use of
      amoxicillin/clavulanate (ACA) using outcome measures obtained from a physician
      survey and medical literature. Third-tier therapy was modeled as pathogen
      specific and curative. It could follow one of three pathways: 1) intramuscular
      ceftriaxone; 2) oral fluconazole; or 3) hospitalization for intravenous
      antibiotics. Third-tier outcomes were based on a physician survey. Cost data were
      obtained from standard references and presented from a payer perspective.
      RESULTS: The expected therapeutic costs were 249.40 dollars for the CD pathway
      and 265.44 dollars for the OFX pathway. The estimated number of OFDs per episode
      of care was 25.88 for the CD pathway and 23.86 for the OFX pathway. The cost
      effectiveness ratios for CD and OFX therapies were 9.64 dollars and 11.13 dollars
      per OFD, respectively. CONCLUSION: CD is both more effective and less costly than
      OFX for the treatment of acute otitis media in patients with tympanostomy tubes.

PMID- 16903992
TI  - Estimating the cost-effectiveness of fluticasone propionate for treating chronic
      obstructive pulmonary disease in the presence of missing data.
AB  - OBJECTIVES: To explore the cost-effectiveness of fluticasone propionate (FP) for
      the treatment of chronic obstructive pulmonary disease (COPD), we estimated costs
      and quality-adjusted life-years (QALYs) over 3 years, based on an economic
      appraisal of a previously reported clinical trial (Inhaled Steroids in
      Obstructive Lung Disease in Europe [ISOLDE]). METHODS: Seven hundred forty-two
      patients enrolled in the ISOLDE trial who received either FP or placebo had data
      available on health-care costs and quality of life over the period of the study.
      The SF-36-based utility scores for quality of life were used to calculate QALYs.
      A combined imputation and bootstrapping procedure was employed to handle missing
      data and to estimate statistical uncertainty in the estimated cumulative costs
      and QALYs over the study period. The imputation approach was based on propensity
      scoring and nesting this approach within the bootstrap ensured that multiple
      imputations were performed such that statistical estimates included imputation
      uncertainty. RESULTS: Complete data were available on mortality within the follow
      up period of the study and a nonsignificant trend toward improved survival of
      0.06 (95% confidence interval [CI]-0.01 to 0.15) life-years was observed. In an
      analysis based on a propensity scoring approach to missing data we estimated the
      incremental costs of FP versus placebo to be 1021 sterling pound(95% CI 619-1338
      sterling pound) with an additional effect of 0.11 QALYs (CI 0.04-0.20). Cost
      effectiveness estimates for the within-trial period of 17,700 sterling pound per
      life-year gained (6900 sterling pound to infinity) and 9500 sterling pound per
      QALY gained (CI 4300-26,500 sterling pound) were generated that include
      uncertainty due to the imputation process. An alternative imputation approach did
      not materially affect these estimates. CONCLUSIONS: Previous analyses of the
      ISOLDE study showed significant improvement on disease-specific health status
      measures and a trend toward a survival advantage for treatment with FP. This
      analysis shows that joint considerations of quality of life and survival result
      in a substantial increase in QALYs favoring treatment with FP. Based on these
      data, the inhaled corticosteroid FP appears cost-effective for the treatment of
      COPD. Confirmation or refutation of this result may be achieved once the Towards
      a Revolution in COPD Health (TORCH) study reports, a large randomized controlled
      trial powered to detect mortality changes associated with the use of FP alone, or
      in combination with salmeterol, which is also collecting resource use and utility
      data suitable for estimating cost-effectiveness.

PMID- 16903993
TI  - Managing meningococcal disease in the United States: Hospital case
      characteristics and costs by age.
AB  - OBJECTIVE: Meningococcal disease occurs worldwide. Approximately 1400 to 2800
      cases are reported in the United States annually. The goal of this analysis was
      to examine hospitalized cases of meningitis and meningococcemia to identify case
      characteristics, resource use, and inpatient care costs. METHODS: International
      Classification of Diseases-9th Revision-Clinical Modification diagnosis codes
      036.0-036.9 were used to identify cases from roughly 1000 hospitals in four all
      payer state discharge databases. Multiyear data (1999-2001) were examined to
      identify demographics, admission month, health service utilization, and hospital
      costs by age group: infant (<1 years), children (1-10 years), adolescent (11-17
      years), young adult (18-22 years), adults (23-49 years), and adults (> or =50
      years). Cost estimates include accommodations, ancillary and physician services,
      reported in 2003 US dollars. RESULTS: Of 1654 cases of meningococcal disease
      identified, meningococcemia was coded for 51%. Adults accounted for 33% of the
      cases. The highest rate of admissions occurred from January through March and 62%
      were admitted via the Emergency Department. Inpatient case fatality rate was
      6.4%; 71% of those who died had meningococcemia. The mean length of stay was 9
      days. Of survivors, 91% were discharged home (1% with intravenous medications and
      11% with other home health-care services) while 7% required further subacute
      inpatient care. The average cost per hospitalization was estimated at 23,294
      dollars per patient. Infants had the lowest average cost per stay (16,793
      dollars) and adolescents had the highest (28,202 dollars). CONCLUSIONS: The
      presence of meningococcemia results in a greater death rate, longer length of
      stay, and increased care costs. Meningococcal disease has substantial economic,
      as well as profound clinical consequences for patients of all ages.

PMID- 16903994
TI  - Probabilistic analysis and computationally expensive models: Necessary and
      required?
AB  - OBJECTIVE: To assess the importance of considering decision uncertainty, the
      appropriateness of probabilistic sensitivity analysis (PSA), and the use of
      patient-level simulation (PLS) in appraisals for the National Institute for
      Health and Clinical Excellence (NICE). METHODS: Decision-makers require estimates
      of decision uncertainty alongside expected net benefits (NB) of interventions.
      This requirement may be difficult in computationally expensive models, for
      example, those employing PLS. NICE appraisals published up until January 2005
      were reviewed to identify those where the assessment group utilized a PLS model
      structure to estimate NB. After identifying PLS models, all appraisals published
      in the same year were reviewed. RESULTS: Among models using PLS, one out of six
      conducted PSA, compared with 16 out of 24 cohort models. Justification for
      omitting PSA was absent in most cases. Reasons for choosing PLS included
      treatment switching, sampling patient characteristics and dependence on patient
      history. Alternative modeling approaches exist to handle these, including semi
      Markov models and emulators that eliminate the need for two-level simulation.
      Stochastic treatment switching and sampling baseline characteristics do not
      inform adoption decisions. Modeling patient history does not necessitate PLS, and
      can depend on the software used. PLS addresses nonlinear relationships between
      patient variability and model outputs, but other options exist. Increased
      computing power, emulators or closed-form approximations can facilitate PSA in
      computationally expensive models. CONCLUSIONS: In developing models analysts
      should consider the dual requirement of estimating expected NB and characterizing
      decision uncertainty. It is possible to develop models that meet these
      requirements within the constraints set by decision-makers.

PMID- 16903995
TI  - Indirect costs and cost-effectiveness analysis.
AB  - This article examines the methodological implications of the societal perspective
      in cost-effectiveness analyses in which the costs of health-care interventions
      are defined as the sums of direct and indirect costs. In the model of cost
      effectiveness analysis in which the planner distributes patients among many
      treatments for many illnesses, the definition requires that total indirect costs
      be constrained, and the article proposes an iterative computational procedure for
      choosing a constraint under the assumption that the planner maintains a target
      trade-off rate between losses of health benefits and reductions in indirect
      costs. In the more common model in which the planner decides which of two
      treatments for one illness to provide to patients, the adoption of a societal
      perspective introduces ambiguities into the welfare properties of the decision
      rule, and in general the conclusion that a treatment is cost-effective is valid
      only if switching or assigning patients to the cost-effective treatment does not
      increase the planner's total direct costs.

PMID- 16903996
TI  - Comparing the EQ-5D and the SF-6D descriptive systems to assess their ceiling
      effects in the US general population.
AB  - OBJECTIVES: The EuroQol (EQ-5D) and SF-6D (derived from the SF-12) were compared
      to assess any ceiling effect in the EQ-5D and the SF-6D descriptive systems. In
      addition, the Physical Component Summary (PCS-12), the Mental Component Summary
      (MCS-12) and the EuroQol Visual Analog Scale (EQ-VAS) were compared on their
      discriminative ability to detect differences among individuals with different
      morbidities and sociodemographic characteristics. METHODS: Data from the 2000
      Medical Expenditure Panel Survey were used for the analysis. A total of 11,248
      individuals that were 18 years or older and had data on all the study variables
      were included in the analysis. RESULTS: A total of 5104 individuals (47%)
      reported no limitations on all of the EQ-5D dimensions and only 683 (5.8%) were
      classified in full health based on the SF-6D descriptive system. Approximately
      49% of the respondents that reported no limitations on the EQ-5D reported feeling
      "tense or downhearted and low,""a little," (level 2) or "some" (level 3) of the
      time on SF-6D. PCS-12 scores and EQ-VAS scores among individuals reporting no
      limitations on the EQ-5D descriptive system were significantly lower for
      respondents reporting coronary heart disease, angina, diabetes, myocardial
      infarction, high blood pressure or joint pain compared with respondents that
      reported no medical condition. Effect sizes for medical conditions using the PCS
      12 were larger than the effect sizes using the EQ-VAS. CONCLUSIONS: Unlike the EQ
      5D descriptive system, the SF-6D descriptive system derived from the SF-12 does
      not seem to have a ceiling effect. Nevertheless, the SF-6D does not discriminate
      between individuals with different morbidities who report full health on the EQ
      5D, as does the PCS-12 and the EQ-VAS.

PMID- 16903997
TI  - Fraction of nursing home admissions attributable to urinary incontinence.
AB  - OBJECTIVE: To calculate the proportion of nursing home admissions of the elderly
      that is attributable to urinary incontinence (UI). METHODS: The fraction of
      nursing home admissions attributable to UI was computed from published values for
      the prevalence of UI and relative risks corrected for variables independently
      associated with nursing home admission. RESULTS: The attributable fraction of
      nursing home admissions due to UI in the elderly population was 0.10 (95%
      confidence interval [CI] 0.08-0.13) for men and 0.06 (95% CI 0.05-0.09) for
      women. Extrapolation to the US population in 2000 suggests an annualized cost of
      nursing home admissions due to UI of 6.0 billion dollars (3.0 billion dollars
      each for elderly men and women). CONCLUSIONS: The estimates of the fraction of
      nursing home admissions attributable to UI exceed those previously assumed and
      show an imbalance between the sexes. Policies that support reimbursement for
      treatments of UI in the community might help prevent or delay
      institutionalization and offset some of the costs.

PMID- 16903998
TI  - Applying the grid computation in long-term retrospective health insurance data
      analysis.

PMID- 16903999
TI  - Is rosuvastatin really a more efficient therapeutic option than atorvastatin?

PMID- 16904001
TI  - Protein-protein interaction networks in the spinocerebellar ataxias.
AB  - A large yeast two-hybrid study investigating whether the proteins mutated in
      different forms of spinocerebellar ataxia have interacting protein partners in
      common suggests that some forms do share common pathways, and will provide a
      valuable resource for future work on these diseases.

PMID- 16904002
TI  - Caveolin-1 and -2 in airway epithelium: expression and in situ association as
      detected by FRET-CLSM.
AB  - BACKGROUND: Caveolae are involved in diverse cellular functions such as signal
      transduction, cholesterol homeostasis, endo- and transcytosis, and also may serve
      as entry sites for microorganisms. Hence, their occurrence in epithelium of the
      airways might be expected but, nonetheless, has not yet been examined. METHODS:
      Western blotting, real-time quantitative PCR analysis of abraded tracheal
      epithelium and laser-assisted microdissection combined with subsequent mRNA
      analysis were used to examine the expression of cav-1 and cav-2, two major
      caveolar coat proteins, in rat tracheal epithelium. Fluorescence
      immunohistochemistry was performed to locate caveolae and cav-1 and -2 in the
      airway epithelium of rats, mice and humans. Electron-microscopic analysis was
      used for the identification of caveolae. CLSM-FRET analysis determined the
      interaction of cav-1alpha and cav-2 in situ. RESULTS: Western blotting and laser
      assisted microdissection identified protein and transcripts, respectively, of cav
      1 and cav-2 in airway epithelium. Real-time quantitative RT-PCR analysis of
      abraded tracheal epithelium revealed a higher expression of cav-2 than of cav-1.
      Immunoreactivities for cav-1 and for cav-2 were co-localized in the cell membrane
      of the basal cells and basolaterally in the ciliated epithelial cells of large
      airways of rat and human. However, no labeling for cav-1 or cav-2 was observed in
      the epithelial cells of small bronchi. Using conventional double-labeling
      indirect immunofluorescence combined with CLSM-FRET analysis, we detected an
      association of cav-1alpha and -2 in epithelial cells. The presence of caveolae
      was confirmed by electron microscopy. In contrast to human and rat, cav-1
      immunoreactivity and caveolae were confined to basal cells in mice. Epithelial
      caveolae were absent in cav-1-deficient mice, implicating a requirement of this
      caveolar protein in epithelial caveolae formation. CONCLUSION: These results show
      that caveolae and caveolins are integral membrane components in basal and
      ciliated epithelial cells, indicating a crucial role in these cell types. In
      addition to their physiological role, they may be involved in airway infection.

PMID- 16904003
TI  - Time-related improvement of survival in resectable gastric cancer: the role of
      Japanese-style gastrectomy with D2 lymphadenectomy and adjuvant chemotherapy.
AB  - BACKGROUND: We investigated the change of prognosis in resected gastric cancer
      (RGC) patients and the role of radical surgery and adjuvant chemotherapy.
      METHODS: We retrospectively analyze the outcome of 426 consecutive patients from
      1975 to 2002, divided into 2 time-periods (TP) cohort: Before 1990 (TP1, n = 207)
      and 1990 or after (TP2; n= 219). Partial gastrectomy and D1-lymphadenectomy was
      predominant in TP1 and total gastrectomy with D2-lymphadenectomy it was in TP2.
      Adjuvant chemotherapy consisted of mitomycin C (MMC), 10-20 mg/m2 i.v. 4 courses
      or MMC plus Tegafur 500 mg/m2 for 6 months. RESULTS: Positive nodes were similar
      in TP2/TP1 patients with 56%/59% respectively. Total gastrectomy was done in
      56%/45% of TP2/TP1 respectively. Two-drug adjuvant chemotherapy was administered
      in 65%/18% of TP2/TP1 respectively. Survival at 5 years was 66% for TP2 versus
      42% for TP1 patients (p < 0.0001). Survival by stages II, IIIA and IIIB for TP2
      versus TP1 patients was 70 vs. 51% (p = 0.0132); 57 vs. 22% (p = 0.0008) and 30
      vs. 15% (p = 0.2315) respectively. Multivariate analysis showed that age, stage
      of disease and period of treatment were independent variables. CONCLUSION: The
      global prognosis and that of some stages have improved in recent years with case
      RGC patients treated with surgery and adjuvant chemotherapy.

PMID- 16904004
TI  - Trends in drop out, drug free discharge and rates of re-presentation: a
      retrospective cohort study of drug treatment clients in the North West of
      England.
AB  - BACKGROUND: Governments aim to increase treatment participation by problematic
      drug users. In the UK this has been achieved by fiscal investment, an expanded
      workforce, reduced waiting times and coercive measures (usually criminal justice
      (CJ) led). No assessment of these measures on treatment outcomes has been made.
      Using established monitoring systems we assessed trends in 'dropped out' and
      'discharged drug free' (DDF), since the launch of the national drug strategy, and
      rates of treatment re-presentation for these cohorts. METHODS: A longitudinal
      dataset of drug users (1997 to 2004/05, n = 26,415) was used to identify people
      who dropped out of, and were DDF from, services for years 1998 to 2001/02, and re
      presentations of these people in years to 2004/05. Trends in drop out and DDF,
      baseline comparisons of those DDF and those who dropped out and outcome
      comparisons for those referred from the CJ system versus other routes of referral
      were examined using chi square. Logistic regression analyses identified variables
      predicting drop out versus DDF and subsequent re-presentation versus no re
      presentation. RESULTS: The proportion of individuals dropping out has increased
      from 7.2% in 1998 to 9.6% in 2001/02 (P < 0.001). The proportion DDF has fallen
      from 5.8% to 3.5% (P < 0.001). Drop out was more likely in later years, by those
      of younger age and by CJ referrals. The proportion re-presenting to treatment in
      the following year increased from 27.8% in 1998 to 44.5% in 2001/02 (P < 0.001)
      for those DDF, and from 22.9% to 48.6% (P < 0.001) for those who dropped out.
      Older age and prior treatment experience predicted re-presentation. Outcome (drop
      out or DDF) did not predict re-presentation. CONCLUSION: Increasing numbers in
      treatment is associated with an increased proportion dropping out and an ever
      smaller proportion DDF. Rates of drop out are significantly higher for those
      coerced into treatment via the CJ system. Rates of re-presentation are similar
      for those dropping out and those DDF. Encouragingly, those who need to re-engage
      with treatment, particularly those who drop out, are doing so more quickly. The
      impact of coercion on treatment outcomes and the appropriateness of aftercare
      provision require further consideration.

PMID- 16904005
TI  - A genome-wide approach to identify genetic loci with a signature of natural
      selection in the Irish population.
AB  - BACKGROUND: In this study we present a single population test (Ewens-Waterson)
      applied in a genomic context to investigate the presence of recent positive
      selection in the Irish population. The Irish population is an interesting focus
      for the investigation of recent selection since several lines of evidence suggest
      that it may have a relatively undisturbed genetic heritage. RESULTS: We first
      identified outlier single nucleotide polymorphisms (SNPs), from previously
      published genome-wide data, with high FST branch specification in a European
      American population. Eight of these were chosen for further analysis. Evidence
      for selective history was assessed using the Ewens-Watterson's statistic
      calculated using Irish genotypes of microsatellites flanking the eight outlier
      SNPs. Evidence suggestive of selection was detected in three of these by
      comparison with a population-specific genome-wide empirical distribution of the
      Ewens-Watterson's statistic. CONCLUSION: The cystic fibrosis gene, a disease that
      has a world maximum frequency in Ireland, was among the genes showing evidence of
      selection. In addition to the demonstrated utility in detecting a signature of
      natural selection, this approach has the particular advantage of speed. It also
      illustrates concordance between results drawn from alternative methods
      implemented in different populations.

PMID- 16904006
TI  - Determinants of fruit and vegetable consumption among children and adolescents: a
      review of the literature. Part I: Quantitative studies.
AB  - BACKGROUND: In order to more effectively promote fruit and vegetable intake among
      children and adolescents, insight into determinants of intake is necessary. We
      conducted a review of the literature for potential determinants of fruit and
      vegetable intake in children and adolescents. METHODS: Papers were identified
      from Medline and PsycINFO by using all combinations of the search terms:
      "fruit(s) or vegetable(s)" and "children or adolescents". Quantitative research
      examining determinants of fruit and/or vegetable intake among children and
      adolescents aged 6-18 years were included. The selection and review process was
      conducted according to a four-step protocol resulting in information on country,
      population, design, methodology, theoretical basis, instrument used for measuring
      intake, statistical analysis, included independent variables, and effect sizes.
      RESULTS: Ninety-eight papers were included. A large number of potential
      determinants have been studied among children and adolescents. However, for many
      presumed determinants convincing evidence is lacking, mostly because of paucity
      of studies. The determinants best supported by evidence are: age, gender, socio
      economic position, preferences, parental intake, and home
      availability/accessibility. Girls and younger children tend to have a higher or
      more frequent intake than boys and older children. Socio-economic position,
      preferences, parental intake, and home availability/accessibility are all
      consistently positively associated with intake. CONCLUSION: The determinants most
      consistently supported by evidence are gender, age, socio-economic position,
      preferences, parental intake and home availability/accessibility. There is a need
      for internationally comparative, longitudinal, theory-based and multi-level
      studies taking both personal and environmental factors into account. This paper
      is published as part of the special Pro Children series in the International
      Journal of Behavioral Nutrition and Physical Activity. Please see
      [http://www.ijbnpa.org/content/3/1/26] for the relevant editorial.

PMID- 16904007
TI  - PeanutMap: an online genome database for comparative molecular maps of peanut.
AB  - BACKGROUND: Molecular maps have been developed for many species, and are of
      particular importance for varietal development and comparative genomics. However,
      despite the existence of multiple sets of linkage maps, databases of these data
      are lacking for many species, including peanut. DESCRIPTION: PeanutMap
      http://peanutgenetics.tamu.edu/cmap provides a web-based interface for viewing
      specific linkage groups of a map set. PeanutMap can display and compare multiple
      maps of a set based upon marker or trait correspondences, which is particularly
      important as cultivated peanut is a disomic tetraploid. The database can also
      compare linkage groups among multiple map sets, allowing identification of
      corresponding linkage groups from results of different research projects. Data
      from the two published peanut genome map sets, and also from three maps sets of
      phenotypic traits are present in the database. Data from PeanutMap have been
      incorporated into the Legume Information System website http://www.comparative
      legumes.org to allow peanut map data to be used for cross-species comparisons.
      CONCLUSION: The utility of the database is expected to increase as several SSR
      based maps are being developed currently, and expanded efforts for comparative
      mapping of legumes are underway. Optimal use of these data will benefit from the
      development of tools to facilitate comparative analysis.

PMID- 16904008
TI  - A high-density consensus map of barley linking DArT markers to SSR, RFLP and STS
      loci and agricultural traits.
AB  - BACKGROUND: Molecular marker technologies are undergoing a transition from
      largely serial assays measuring DNA fragment sizes to hybridization-based
      technologies with high multiplexing levels. Diversity Arrays Technology (DArT) is
      a hybridization-based technology that is increasingly being adopted by barley
      researchers. There is a need to integrate the information generated by DArT with
      previous data produced with gel-based marker technologies. The goal of this study
      was to build a high-density consensus linkage map from the combined datasets of
      ten populations, most of which were simultaneously typed with DArT and Simple
      Sequence Repeat (SSR), Restriction Enzyme Fragment Polymorphism (RFLP) and/or
      Sequence Tagged Site (STS) markers. RESULTS: The consensus map, built using a
      combination of JoinMap 3.0 software and several purpose-built perl scripts,
      comprised 2,935 loci (2,085 DArT, 850 other loci) and spanned 1,161 cM. It
      contained a total of 1,629 'bins' (unique loci), with an average inter-bin
      distance of 0.7 +/- 1.0 cM (median = 0.3 cM). More than 98% of the map could be
      covered with a single DArT assay. The arrangement of loci was very similar to,
      and almost as optimal as, the arrangement of loci in component maps built for
      individual populations. The locus order of a synthetic map derived from merging
      the component maps without considering the segregation data was only slightly
      inferior. The distribution of loci along chromosomes indicated centromeric
      suppression of recombination in all chromosomes except 5H. DArT markers appeared
      to have a moderate tendency toward hypomethylated, gene-rich regions in distal
      chromosome areas. On the average, 14 +/- 9 DArT loci were identified within 5 cM
      on either side of SSR, RFLP or STS loci previously identified as linked to
      agricultural traits. CONCLUSION: Our barley consensus map provides a framework
      for transferring genetic information between different marker systems and for
      deploying DArT markers in molecular breeding schemes. The study also highlights
      the need for improved software for building consensus maps from high-density
      segregation data of multiple populations.

PMID- 16904009
TI  - Prevalence of self-reported hypertension and its relation to dietary habits, in
      adults; a nutrition & health survey in Greece.
AB  - BACKGROUND: Hypertension leads to many degenerative diseases, the most common
      being cardiovascular in origin. This study has been designed to estimate the
      prevalence of self-reported hypertension in a random nationwide sample of adult
      Greek population, while focus was set to the assessment of participants'
      nutritional habits in relation to their hypertension status. METHODS: A random
      digit dialed telephone survey. Based on a multistage, stratified sampling, 5003
      adults (18 - 74 yr) participated (men: 48.8%, women: 51.2%). All participants
      were interviewed via telephone by trained personnel who used a standard
      questionnaire. The questionnaire included demographic and socioeconomic
      characteristics, medical history, lifestyle habits and nutritional assessment.
      RESULTS: The prevalence of self-reported hypertension was 13.3% in men and 17.7%
      in women (P < 0.001). Furthermore, women reported higher values of systolic blood
      pressure (180 +/- 27 mmHg) than men (169 +/- 24 mmHg). Positive relationships
      were found between hypertension status and the prevalence of the rest
      investigated health conditions (i.e. hypercholesterolaemia, diabetes mellitus,
      renal failure and obesity). Nutritional assessment showed that consumption of
      fish, fruits and juices, cereals, and low fat milk and yogurt was significantly
      higher among hypertensive subjects while the opposite was observed for food items
      as red meat, pork, egg, pasta and rice, full fat dairy products and desserts.
      CONCLUSION: Hypertension seems to be a serious public health problem in Greece.
      It is encouraging that hypertensives may have started adopting some more healthy
      nutritional behaviour compared to normotensive ones. However, they can gain
      significant benefits regarding to blood pressure control, if they increase the
      level of compliance with dietary recommendations.

PMID- 16904010
TI  - Health related quality of life trajectories and predictors following coronary
      artery bypass surgery.
AB  - BACKGROUND: Many studies have demonstrated that health related quality of life
      (HRQoL) improves, on average, after coronary artery bypass graft surgery (CABGS).
      However, this average improvement may not be realized for all patients, and it is
      possible that there are two or more distinctive groups with different, possibly
      non-linear, trajectories of change over time. Furthermore, little is known about
      the predictors that are associated with these possible HRQoL trajectories after
      CABGS. METHODS: 182 patients listed for elective CABGS at The Royal Melbourne
      Hospital completed a postal battery of questionnaires which included the Short
      Form-36 (SF-36), Profile of Mood States (POMS) and the Everyday Functioning
      Questionnaire (EFQ). These data were collected on average a month before surgery,
      and at two months and six months after surgery. Socio-demographic and medical
      characteristics prior to surgery, as well as surgical and post-surgical
      complications and symptoms were also assessed. Growth curve and growth mixture
      modelling were used to identify trajectories of HRQoL. RESULTS: For both the
      physical component summary scale (PCS) and the mental component summary scale
      (MCS) of the SF-36, two groups of patients with distinct trajectories of HRQoL
      following surgery could be identified (improvers and non-improvers). A series of
      logistic regression analyses identified different predictors of group membership
      for PCS and MCS trajectories. For the PCS the most significant predictors of non
      improver membership were lower scores on POMS vigor-activity and higher New York
      Heart Association dyspnoea class; for the MCS the most significant predictors of
      non-improver membership were higher scores on POMS depression-dejection and
      manual occupation. CONCLUSION: It is incorrect to assume that HRQoL will improve
      in a linear fashion for all patients following CABGS. Nor was there support for a
      single response trajectory. It is important to identify characteristics of each
      patient, and those post-operative symptoms that could be possible targets for
      intervention to improve HRQoL outcomes.

PMID- 16904012
TI  - The internet 2006.
AB  - Each year Developmental Medicine and Child Neurology (DMCN) invites the President
      Elect of the American Academy for Cerebral Palsy and Developmental Medicine
      (AAPCDM) to compose a guest editorial. As we mark the 60th anniversary of the
      Academy, I welcome the opportunity to make a few observations on the emergence of
      the internet as a medium that, within the space of two decades, has had an
      increasing influence upon both medical research and its dissemination throughout
      the world. Although the Academy's founding fathers certainly recognized that
      communication was the key to future progress, it is unlikely that they could have
      imagined what was ahead in terms of instantaneous information exchange or how
      that capability would promote collaboration at great distances, speed up the
      decoding of the human genome, and empower patients with information that
      previously had largely been the province of academia. This September, portions of
      our annual meeting will be webcast from Boston to 10 locations in four different
      countries around the world. Individuals who cannot attend the meeting in person
      will have an opportunity to view the lectures, and then, in special sessions, to
      engage in real-time exchanges with many of the presenters. In addition, the
      AACPDM now presents a monthly 1-hour webcast for entitled members concentrating
      on timely subjects by world-renowned authorities.

PMID- 16904011
TI  - Detecting the limits of regulatory element conservation and divergence estimation
      using pairwise and multiple alignments.
AB  - BACKGROUND: Molecular evolutionary studies of noncoding sequences rely on
      multiple alignments. Yet how multiple alignment accuracy varies across sequence
      types, tree topologies, divergences and tools, and further how this variation
      impacts specific inferences, remains unclear. RESULTS: Here we develop a
      molecular evolution simulation platform, CisEvolver, with models of background
      noncoding and transcription factor binding site evolution, and use simulated
      alignments to systematically examine multiple alignment accuracy and its impact
      on two key molecular evolutionary inferences: transcription factor binding site
      conservation and divergence estimation. We find that the accuracy of multiple
      alignments is determined almost exclusively by the pairwise divergence distance
      of the two most diverged species and that additional species have a negligible
      influence on alignment accuracy. Conserved transcription factor binding sites
      align better than surrounding noncoding DNA yet are often found to be misaligned
      at relatively short divergence distances, such that studies of binding site gain
      and loss could easily be confounded by alignment error. Divergence estimates from
      multiple alignments tend to be overestimated at short divergence distances but
      reach a tool specific divergence at which they cease to increase, leading to
      underestimation at long divergences. Our most striking finding was that overall
      alignment accuracy, binding site alignment accuracy and divergence estimation
      accuracy vary greatly across branches in a tree and are most accurate for
      terminal branches connecting sister taxa and least accurate for internal branches
      connecting sub-alignments. CONCLUSION: Our results suggest that variation in
      alignment accuracy can lead to errors in molecular evolutionary inferences that
      could be construed as biological variation. These findings have implications for
      which species to choose for analyses, what kind of errors would be expected for a
      given set of species and how multiple alignment tools and phylogenetic inference
      methods might be improved to minimize or control for alignment errors.

PMID- 16904013
TI  - Low doses of pamidronate for the treatment of osteopenia in non-ambulatory
      children.
AB  - In recent years, bisphosphonates, primarily intravenous (iv) pamidronate, have
      become very widely used in children with severe osteogenesis imperfecta (OI).
      This has occurred without the well-controlled clinical trials usually required
      before a medication becomes 'standard care'. Without placebo-controlled trials it
      is difficult to define precisely the risks and the benefits, but in children with
      very severe OI and numerous fractures the risk/benefit ratio is so clearly
      favorable that widespread use of pamidronate in this situation appears
      appropriate.

PMID- 16904014
TI  - Low doses of pamidronate to treat osteopenia in children with severe cerebral
      palsy: a pilot study.
AB  - The aim of this study was to test the efficacy of low doses of pamidronate in
      increasing bone mineral density (BMD) in non-ambulatory children and adolescents
      with cerebral palsy (CP). Twenty-three non-ambulatory children and adolescents
      (12 females, 11 males; mean age 10y [SD 5y], range 4y 1 mo-17 y 11 mo) with
      severe spastic quadriplegic CP and low BMD were recruited from a
      multidisciplinary clinic. Severity of CP was graded at Level IV (n=10) and Level
      V (n=13) using the Gross Motor Function Classification System. Patients received
      intravenous pamidronate (4.12 mg/kg/y, maximum 45 mg/d) every 4 months. Lumbar
      spine and femoral neck BMD were measured at baseline and after 4 and 12 months.
      Twelve months after the first dose of pamidronate there was a significant
      increase in lumbar spine and femoral neck BMD (p<0.01 for both sites) and z
      scores compared with baseline values (p<0.01 for both sites). Mean BMD z scores
      increased 1.6 points for femoral neck and 1.9 points for lumbar spine after 12
      months of pamidronate treatment. Serum intact parathyroid hormone increased
      significantly and cross-linked N-teleopeptide of type I collagen decreased
      significantly at 12 months. No significant side effect was noted. Low doses of
      pamidronate are well tolerated and significantly increase BMD in non-ambulatory
      children and adolescents with CP.

PMID- 16904015
TI  - Eating and feeding are not the same: caregivers' perceptions of gastrostomy
      feeding for children with cerebral palsy.
AB  - Using a semi-structured questionnaire, this descriptive study examined
      perceptions of feeding and adherence to feeding recommendations for caregivers
      (26 females; mean age 32y 7mo [SD 9.4y], range 20-59y) of children with cerebral
      palsy (CP) and a gastrostomy tube (GT). Children in the study (15 females, 11
      males; mean age 4y 8mo [SD 3y 11mo], range 8mo-16y) had had a GT in place for at
      least 1 month and been assessed at Level II (n=2), Level III (n=2), Level IV
      (n=5), and Level V (n=17) of the Gross Motor Function Classification System. A
      negative response was reported by 18 caregivers when the GT was recommended;
      however, 21 caregivers reported improvement in the children following placement.
      All children received formula through the GT that was adequate for complete
      nutrition, yet 14 caregivers gave other foods through the GT (e.g. juice, cereal,
      soup, or table food). Of the 17 children receiving oral feedings, meals were an
      unpleasant experience for over half. Of the remaining nine children, in spite of
      a strict nil by mouth recommendation by physicians, five continued to receive
      some oral feedings. Generally, caregivers perceived GT feeding as 'unnatural'.
      Understanding these perceptions will help clinicians to develop effective, family
      centered, patient-appropriate intervention and adherence strategies for GT-fed
      children with CP.

PMID- 16904016
TI  - Impaired motor performance and movement quality in very-low-birthweight children
      at 6 years of age.
AB  - Motor performance and movement quality were quantitatively examined (Zurich
      Neuromotor Assessment: timed motor performances and associated movements) in 87
      prospectively enrolled very-low-birthweight (VLBW; <1250g) children (38 males, 49
      females; mean birthweight 1016.2g [SD 141.5]:, range 720-1240g; mean gestational
      age 28.7wks [SD 2], range 25.7-33.4wks) at 6 years of age. All motor tasks were
      below the reference population: pure motor (median z-score) -0.46; adaptive fine
      motor (pegboard) -0.99; adaptive gross motor -0.88; static balance -0.48; and
      associated movements -1.90. All tasks correlated with the degree of neurological
      abnormalities (p<or=0.004). VLBW children with no neurological abnormality also
      performed below the 10th centile and associated movements occurred more
      frequently than in the reference population (odds ratio 18, 95% confidence
      interval 6.7-47.9). Severity of periventricular leukomalacia and intraventricular
      haemorrhage assessed by ultrasound was associated with adaptive fine and gross
      motor tasks. We conclude that speed of motor performance and movement quality in
      particular were substantially impaired in VLBW children and are related to the
      degree of neurological abnormalities and neonatal cerebral injury.

PMID- 16904017
TI  - Activities of daily living in children with hemiplegic cerebral palsy: a cross
      sectional evaluation using the Assessment of Motor and Process Skills.
AB  - Upper limb impairment can affect the ability to perform and participate in
      activities of daily living. The level of activity and participation limitation in
      the home environment for children with hemiplegic cerebral palsy (CP) is poorly
      understood. A greater understanding of these limitations could be used to provide
      targeted and appropriate intervention programmes. Level of activity and
      participation limitation were investigated, with the use of the Assessment of
      Motor and Process Skills (AMPS) in a representative sample of 54 South Australian
      children (31 males, 23 females) with hemiplegic CP, aged 3 to 12 years (mean age
      7y 4mo [SD 2y 5mo]). Two AMPS tasks that were familiar to the child were
      performed in the home under the supervision of a trained occupational therapist.
      Findings suggested that younger children (3-8y) performed significantly better
      than older children (9-12y) for motor skill ability (0.46 vs 0.09, p=0.041) but
      not for process skill ability (-0.25 vs -0.28, p=0.885). Functional performance
      for the sample was below that of age-matched normative data. Motor performance in
      activities of daily living as detected by the AMPS seemed to worsen with age in
      children with hemiplegic CP. Further investigation into what can influence this
      outcome is required.

PMID- 16904018
TI  - Muscle stiffness and strength and their relation to hand function in children
      with hemiplegic cerebral palsy.
AB  - This study compared the passive stiffness of wrist flexors and the strength of
      wrist flexors and extensors in three different wrist positions (30 degrees of
      flexion, neutral, and 30 degrees of extension) between children with cerebral
      palsy (CP) and typically developing (TD) comparison children. It also examined
      associations between these characteristics and manual function in children with
      CP. Eleven children with spastic hemiplegic CP (six females, five males; mean age
      8y 5mo [SD 1y 8mo], range 6-11y) and 11 TD children, matched for age and sex,
      took part in this study. Passive stiffness of muscles was measured as the
      torque/angle relation during passive motion. Isometric strength tests were
      performed and the time needed to complete three tasks based on the Jebsen-Taylor
      Hand Function Test was recorded. Flexor stiffness was higher in the group with
      CP. Strength of flexors and extensors in the group with CP was lower with the
      wrist extended. No difference among test positions was found in the TD group.
      Moderate correlations were observed between manual function and variables related
      to strength and stiffness of wrist muscles in the group with CP. Children with CP
      showed muscle alterations coherent with the use of the wrist in flexion.
      Intervention on these characteristics could have a positive impact on manual
      function.

PMID- 16904019
TI  - Gross Motor Function Classification System used in adults with cerebral palsy:
      agreement of self-reported versus professional rating.
AB  - The present study investigated the reliability of self-reported rating of Gross
      Motor Function Classification System (GMFCS) levels compared with professional
      rating, and changes in gross motor function over time, in adults with cerebral
      palsy. Twenty-nine females and 33 males aged between 18 years 5 months and 62
      years 11 months (mean age 34y 7mo [SD 10y 6mo]) participated in the study.
      Participants rated their current gross motor function using the GMFCS and
      reported their judgement of their gross motor function at age 10 to 12 years. The
      project leader, a physical therapist, also classified participants' current GMFCS
      levels and conducted a chart review on all accessible medical records of
      participants' gross motor function when they were 10 to 12 years old, rating the
      GMFCS level accordingly. Intraclass correlation coefficients (ICC) between self
      reported and professional ratings showed excellent agreement (ICC=0.93-0.95, 95%
      confidence interval [CI] 0.89-0.97). More than half the participants experienced
      a stable gross motor function from the age of 10 to 12 years to the present.
      Those at GMFCS Levels II and III at the age of 10 to 12 years (according to the
      professional rating) had significant change for the worse in gross motor function
      over time, with odds ratios of 9.30 (95% CI 1.2-73.0, p=0.03) and 7.00 (95% CI
      1.1-43.0, p=0.04) respectively. Interview data on circumstances regarding changes
      in gross motor function since childhood are also reported. Changes in GMFCS level
      were mostly associated with physical or social environmental factors.

PMID- 16904020
TI  - A new motor performance test in a prospective study on children with suspected
      myopathy.
AB  - In the development of a new diagnostic motor performance test to spare more
      children from painful muscle biopsy, seven functional items were used to measure
      muscle strength and muscle endurance in a prospective study on new patients. Over
      a 2-year period, 22 patients (12 males, 10 females; mean age 8y 1mo [SD 2y 6mo],
      range 4-11y) were recruited for the study. They had all been referred with
      suspected myopathy. The motor performance test was administered before muscle
      biopsy. Validity of the seven items was assessed using logistic regression
      analysis and receiver operating characteristic (ROC) analysis. Two items were
      withdrawn from the test because they were not suitable for children aged 4 to 5
      years. The five remaining items were: Heels, Circuit, Stairs, Jump, and Gowers. A
      full logistic regression model including these five items was fitted to the total
      population of 90 patients suspected of having myopathy (from this study and our
      previous study) to make the best prediction of whether myopathy was present. The
      ROC area under the curve of the diagnostic prediction model was 0.92 (95%
      confidence interval [CI] 0.87-0.98) and 0.89 (95% CI 0.87-0.92) after bootstrap
      correction. This indicated the high diagnostic power that can be expected for
      future, similar patients. This non-invasive and child-friendly motor performance
      test can improve diagnostic procedure and, therefore, spare more children from
      unnecessary muscle biopsy.

PMID- 16904021
TI  - Neuromotor development in nocturnal enuresis.
AB  - In children with nocturnal enuresis, a higher rate of minor neurological
      dysfunction has been found. The aim of this study was to assess timed performance
      (a measure of motor performance speed) and associated movements using a
      standardized and reliable instrument. The motor function of 37 children with
      nocturnal enuresis (27 males, 10 females; mean age 10y 7mo [SD 1y 10mo]; age
      range 8y-14y 8mo) and 40 comparison children without enuresis (17 males, 23
      females; mean age 10y 7mo [SD 1y 6mo]; age range 8y-14y 8mo) was assessed using
      the Zurich Neuromotor Assessment. Children with nocturnal enuresis showed a
      slower motor performance than comparison children, particularly for repetitive
      hand and finger movements. This study provides evidence for a maturational
      deficit in motor performance in children with nocturnal enuresis. In addition to
      a maturational deficit of the brainstem, it is proposed that there is a possible
      maturational deficit of the motor cortex circuitry and related cortical areas in
      children with nocturnal enuresis.

PMID- 16904022
TI  - Cerebrospinal fluid insulin-like growth factors IGF-1 and IGF-2 in infantile
      autism.
AB  - There has been little exploration of major biologic regulators of cerebral
      development in autism. We measured insulin-like growth factors (IGF) -1 and -2
      from cerebrospinal fluid (CSF) by radio immunoassay in 25 children with autism
      (median age 5y 5mo; range 1y 11mo-15y 10mo; 20 males, 5 females), and in 16 age
      matched comparison children without disability (median age 7y 4mo; range 1y 1mo
      15y 2mo; eight males, eight females). IGF-1 and -2 concentrations were further
      correlated with age of patients and head size. CSF IGF-1 concentration was
      significantly lower in patients with autism than in the comparison group. The CSF
      concentrations of children with autism under 5 years of age were significantly
      lower than their age-matched comparisons. The head circumferences correlated with
      CSF IGF-1 in children with autism but no such correlation was found in the
      comparison group. There was no difference between the two groups in CSF IGF-2
      concentrations. No patients with autism had macrocephaly. We conclude that low
      concentrations of CSF IGF-1 at an early age might be linked with the pathogenesis
      in autism because IGF-1 is important for the survival of Purkinje cells of the
      cerebellum. The head growth might be explained by the actions of IGF-1 and -2
      reflected in CSF concentrations.

PMID- 16904023
TI  - Pyruvate dehydrogenase E3 binding protein (protein X) deficiency.
AB  - Pyruvate dehydrogenase (PDH) deficiency is a major cause of neurological
      dysfunction and lactic acidosis in infancy and early childhood. The great
      majority of cases (>80%) result from mutations in the X-linked gene for the
      E1alpha subunit of the complex (PDHA1). Mutations in the genes for the other
      subunits have all been described, but only dihydrolipoamide dehydrogenase (E3)
      and E3 binding protein (E3BP) defects contribute significantly to the total
      number of patients with PDH deficiency. Although previously considered rare, with
      only 13 reported cases, we have found that mutations in PDX1, the gene for the E3
      binding protein, are in fact relatively common. Clinical, biochemical, and
      genetic features of six new patients (four males, two females; age range 15mo-6y)
      with mutations in this gene are compared with previously reported cases. All
      patients with E3BP deficiency identified to date have mutations which completely
      prevent synthesis of the protein product. However, they are generally less
      severely affected than patients with PDHA1 mutations, although there is
      considerable overlap in clinical and neuroradiological features.

PMID- 16904024
TI  - Coping with Dravet syndrome: parental experiences with a catastrophic epilepsy.
AB  - The aim of this study was to investigate how parents cope with and care for a
      child with Dravet syndrome, a severe myoclonic epilepsy with three distinct
      stages. Twenty-four parents of children with Dravet syndrome participated in a
      semi-structured interview and 17 completed the Impact of Childhood Neurologic
      Disability Scale (ICND) questionnaire. Children included 11 males and 13 females
      aged 2 to 24 years (mean age 10y 2mo [SD 5y 8mo]). Stage 1 of the syndrome was
      generally very difficult. Uncertainty about the diagnosis was the primary cause
      of stress. Seizure control was worst during this time. The primary concern in
      Stage 2 remained seizure control but developmental, behavioral, and sleep issues
      also emerged. Negative effects were noted in parents' relationships with others.
      Stage 3 brought better seizure control but decreased cognitive level, increased
      behavioral problems, and increasing social isolation for parents. Respite and
      relief care were hard to obtain at each stage. ICND scores mirrored the findings
      of the interviews. The three stages of Dravet syndrome present serious challenges
      for parents. Seizures are persistent and severe but developmental, behavioral,
      and sleep issues add to the stress. In the absence of successful medical
      treatment for Dravet syndrome, further attention needs to be paid to helping
      families cope with the disorder.

PMID- 16904025
TI  - Efficacy of very high dose steroid treatment in a case of Landau-Kleffner
      syndrome.
AB  - Landau-Kleffner syndrome (LKS) is an acquired childhood aphasia associated with
      paroxysmal bitemporal electroencephalogram (EEG) abnormalities and, sometimes,
      clinical seizures. We report the case of a female aged 5 years 6 months who
      presented clinically with apparent hearing loss, deterioration in speech, and
      seizure activity over 12 days. The female had previous detailed speech/language
      assessments at 3 to 4 years of age due to articulation delay. LKS was diagnosed
      on EEG with bitemporal spike and wave activity during sleep. The patient was
      treated with high dose prednisolone 3mg/kg/day, intensive speech/language
      therapy, and followed a modified educational program. We recorded a marked
      regression in receptive and expressive language skills, as well as her speech,
      language, and cognitive profiles before and during treatment with prednisolone,
      during an 18-month follow-up period. The patient demonstrated an excellent
      clinical response highlighting the importance of a multidisciplinary approach to
      management of LKS.

PMID- 16904026
TI  - Recurrent optic neuritis associated with Chlamydia pneumoniae infection of the
      central nervous system.
AB  - It has been suggested that Chlamydia pneumoniae (C. pneumoniae) is involved in
      the pathogenesis of diverse diseases of the central nervous system (CNS),
      including multiple sclerosis. We report the case of a 12-year-old male with
      isolated recurrent optic neuritis and an associated CNS infection with C.
      pneumoniae. The patient presented with three attacks of optic neuritis within 5
      months. A positive polymerase chain reaction for C. pneumoniae in the
      cerebrospinal fluid led to the diagnosis of a CNS infection with C. pneumoniae.
      After treatment with the antibiotic rifampicin, he experienced no further attacks
      during the follow-up period of 6 years. These findings suggest the possibility of
      a C. pneumoniae infection as a contributing factor or even causative event for
      the development of optic neuritis.

PMID- 16904027
TI  - A neurophysiological perspective on sleep and its maturation.
AB  - Neurophysiological studies of sleep have increasingly focused on underlying
      dynamic processes. This would appear particularly relevant to the developmental
      aspects of sleep. Involvement of sleep-dependent mechanisms in emotional
      processing, as well as perceptual-sensory, perceptual-motor, and cognitive
      learning, mostly studied in adults, may play major roles in development. Rapid
      eye movement (REM) sleep, which is generated by complex neuronal interactions
      within the pontine reticular formation, and non-REM sleep, which arises from
      activities in the thalamocortical network, are specifically implicated in
      different aspects of long-term memory systems. They evolve from previous
      physiological and behavioural states which can be traced back to the fetal
      period. Further studies are needed to clearly identify functions reflected by
      hallmarks of sleep stages, such as spindles and K complexes. A better
      understanding of the maturational aspects of sleep should provide important
      insights into physiological development. Assessment approaches taking dynamic
      characteristics of sleep into account may contribute to the design of better
      targeted management of sleep-related problems in neurodevelopmental conditions.

PMID- 16904028
TI  - Activity limitation in hemiplegic cerebral palsy: evidence for disorders in motor
      planning.
AB  - Review of the definition of cerebral palsy (CP) has focused on disorders of
      movement and posture development that cause activity limitations. Recent research
      provides new insights into CP, showing that activity limitation in individuals
      with hemiplegic CP is not exclusively caused by disorders related to movement
      execution, but is also related to the planning of movements. In this review
      article, converging evidence is presented suggesting that, in addition to
      movement execution impairments, impairments in movement planning may also limit
      the performance of activities of daily living. Evidence from studies of fingertip
      force planning and anticipatory planning in object manipulation tasks is
      discussed.

PMID- 16904030
TI  - [Educational practice in health institutions].

PMID- 16904031
TI  - [The scope of educational strategy in teaching education of visiting professors].
AB  - INTRODUCTION: Professors of Medicine usually lack teaching education apart from
      their speciality. This kind of education and the development of researchers in
      education are now a priority. OBJECTIVE: To evaluate the scope of the visit of
      professors in the development of aptitude for critical reading of reports on
      educational research and educational texts in a teaching-education program.
      MATERIALS AND METHODS: An educational strategy was implemented to promote the
      development of a stance on education and on aptitudes for criticism of
      educational texts and research reports, which were assessed by means of
      previously validated instruments. A group of 10 professors was studied. RESULTS:
      After the course, all the participants increased their scores. A p = 0.005 value
      was obtained with the Wilcoxon test in the three instruments applied. All the
      participants showed a stance on education in the retest. CONCLUSIONS: The
      educational strategy modified and increased the professors' stance on education.
      The results showed a significant change of stance for critical reading. Even
      though they are incipient, these results should be encouraged through continuing
      formation of teaching education.

PMID- 16904032
TI  - [Probability of control of the patient with diabetes exclusively treated with
      pharmacological therapy].
AB  - OBJECTIVE: to predict the probability of blood glucose control in patients with
      type-2 diabetes mellitus, exclusively treated with pharmacology therapy. MATERIAL
      AND METHODS: secondary analysis of a database to evaluate the therapeutic
      attachment in type-2 diabetics older than 60 years old. We interviewed 123
      patients in their home to get information about sociodemographic aspects and
      diabetes characteristics. The blood glucose control was measured through glycated
      hemoglobin and the attachment to the pharmacological treatment was measured by
      the Morisky-Green test. The analysis included simple logistic regression; the
      calculation of probability of control for different levels of therapeutic
      attachment was estimated using the result of the regression equation (y) and
      applying the formula 1/1 + e(-y). RESULTS: Monotherapy was present in 82.1%,
      glibenclamide was prescribed alone in 77.2%, glycated hemoglobin average was 11.5
      +/- 3.5 %, 18% of the population was controlled and 58.1% showed some attachment
      to the pharmacological treatment. With a total attachment to the pharmacological
      prescription, the control probability is 27%, and without it, it corresponds to
      10%. CONCLUSION: Almost three out of ten patients with a total attachment to the
      pharmacological treatment have chances of being controlled.

PMID- 16904033
TI  - [Sensitivity and predictive value of the Johnson and Toshach method to estimate
      fetal weight].
AB  - INTRODUCTION: Several clinical methods have been used to follow up fetal growth,
      mainly based in uterine enlargement. Ultrasound (US) is nowadays the main tool to
      evaluate fetal growth; however, is not widely available. Thus, we decided to
      evaluate the Johnson and Toshach method (JTM) to predict newborns weight on
      clinical basis. OBJECTIVE: to evaluate the sensitivity and positive predictive
      value of the JTM. We selected 132 women with single term pregnancies whose
      gestational age was previously confirmed by US, and followed the method described
      by JTM. At the end of pregnancies by delivery or cesarean section, we compared
      our estimations with the newborn infant's weight. In order to avoid bias, only
      women whose pregnancies ended in the following 72 hours were included. All
      clinical measurements were done by one observer. The sensitivity, specificity and
      positive predictive value of the JTM were calculated. RESULTS: We found non
      significant difference between the mean of the fetal weight (3,295 g) calculated
      with the JTM and the mean of the newborn infants weight (3,343 g) (p = NS). The
      standard deviation was 325 g and the standard error mean was >or=53 g or 16 g/kg
      (error = 1.6%). In normal weight groups of neonates, the JTM had a sensitivity of
      97%, a specificity of 71% and the positive predictive value was 98%. We observed
      a higher sensitivity in the detection of macrosomy (80%) than of low-weight
      newborns (33%), but with an inverted specificity of 71.4% vs. 99.2%,
      respectively. CONCLUSION: The JTM is a useful clinical technique to estimate
      fetal weight in the third trimester of gestation that may be applied when US is
      not available, being more sensitive to detect normal weight than macrosomic or
      low-weight newborns.

PMID- 16904034
TI  - [Identification of risk factors in relatives of type-2 diabetics].
AB  - OBJECTIVE: To identify risk factors and warning signs in a sample of first-degree
      relatives of type-2 diabetics at the Family Medicine Unit 2 of the General
      Hospital in Irapuato, Guanajuato, Mexico. MATERIAL AND METHODS: In a non
      probabilistic sample of 360 relatives, a 14-item questionnaire was applied to
      measure abdominal perimeter and body mass index (obesity and overweight), eating
      habits, addictions and sedentarism. The questionnaire was made by general consent
      of experts, by applying Cronbach's alpha reliability coefficient. Specific rates
      of prevalence by sex and age groups were estimated. RESULTS: 233 (65%) relatives
      were females. As part of their family history background, arterial hypertension
      was recorded in 263 (73%) and acute myocardial infarction in 97 (27%). Among the
      dangerous food for health consumed by the relatives of diabetics are cola drinks
      in 94.7%, red meat in 83%, candies in 74.7% and chips in 65.8%; only half of them
      consumed fresh fruits and vegetables; a quarter of them ate prickly pears or
      whole wheat bread. There were 163 (45.3%) persons with high-risk abdominal
      perimeter, and sedentarism was present in 267 (74.2%). However, obesity was 3
      times more frequent in females, but excessive drinking or smoking habits were 7
      times more prevailing in males. CONCLUSIONS: A high-risk behavior was
      demonstrated among relativies of diabetic patients. Therefore, a public-health
      educational program is required to modify risky habits. A change towards
      prevention rather than cure is much needed in health staff.

PMID- 16904035
TI  - [Learning approaches used by undergraduate interns in the development of a
      medical specialty].
AB  - INTRODUCTION: Two learning approaches are examined: a superficial and a profound
      one. The purpose of the first one is to pass the subjects with the minimum
      effort; in the second one, there is a genuine interest in grasping knowledge and
      being acknowledged for one's achievements. The objective of this research was to
      identify the learning approach of undergraduate interns, according to sex, age,
      specialty and grade. MATERIAL AND METHODS: An analysis of conglomerates was used
      as a statistical tool. The sample was formed by 179 undergraduate interns of 19
      medical and surgical specialties offered at a concentration hospital. The form R
      SPQ-2F, proposed by Biggs, was used as an instrument. The reliability and
      validity of the instrument was estimated by means of Cronbach's alpha and
      factorial analysis of learning. RESULTS: 60.3% of the students had a deep
      approach to learning; women and students older than 28 years old in greater
      proportion, as well as those studying internal medicine and those in the third
      year. CONCLUSIONS: Undergraduate interns are students with a high level of
      participation in their own learning process. This is probably due to the demands
      of the profession, the filters of selection and the nature of the subjects.

PMID- 16904036
TI  - [Metabolic syndrome in adults from 20 to 40 years old in a rural Mexican
      community].
AB  - INTRODUCTION: Metabolic syndrome is the main health problem in Mexico. Its two
      principal complications (ischemic cardiopathy and type-2 diabetes) are the two
      main causes of death in Mexico since 2000. OBJECTIVE: To describe the prevalence
      of the metabolic syndrome in adults from 20 to 40 years old in a Mexican rural
      community (Senegal de Palomas, San Juan del Rio, Queretaro) using the National
      Cholesterol Education Program (NCEP III) definition. MATERIAL AND METHODS: A
      descriptive study with a random sample was carried out. We present a univariate
      analysis with a 95% confidence interval. RESULTS: 73 cases were studied. The
      prevalence of the metabolic syndrome was 45.2% slightly higher in men (48.4%)
      than in women (42.8%). The prevalence of hypertension was 27.3%. The prevalence
      of obesity was 26.1% using the definition of the WHO and this prevalence rises up
      to 49.4% using the definition of the Mexican Official Norm. 90.5% of women and
      93.5% of men had low HDLc. CONCLUSIONS: The prevalence of metabolic syndrome in
      adults from 20 to 40 years old in this Mexican rural community is much higher
      than the national mean for the same age cohort. The results show the necessity to
      increase the research of our rural communities in order to identify the possible
      causes to this problem and to create therapeutic programs for patients with
      metabolic syndrome.

PMID- 16904037
TI  - [What is the Institutional Teaching Career?].
AB  - The Instituto Mexicano del Seguro Social carries out a project of enormous
      relevance: to train health attention staff, which is its main function. The
      emergence and progress of a different concept and practice of teaching made
      possible the creation of the Institutional Teaching Career at the end of 2004.
      This achievement represents the acknowledgement of teaching practice, making
      possible the permanence, self-improvement and promotion of those professors truly
      committed to a teaching practice of greater importance at IMSS. The theoretical
      perspective that conceptually frames this career as well as the different
      categories of career professor implies an idea of education, as well as a
      teaching and improvement practice concept of health assistance that outlines a
      way in search of the perfection of both occupations (teaching and assistance) at
      the Instituto Mexicano del Seguro Social, with growing repercussions in its
      influence sphere.

PMID- 16904038
TI  - [Arbovirus causing hemorrhagic fever at IMSS].
AB  - OBJECTIVE: To know the arbovirus causing hemorrhagic fever in patients at the
      Mexican Institute of Social Security. MATERIAL AND METHODS: A follow-up study was
      made in patients with probable diagnosis of hemorrhagic dengue. Blood samples
      were taken to look for dengue fever, yellow fever and San Luis, Tonate and Mayaro
      encephalitis viruses. Frequencies and proportions of the interest variables were
      analyzed. RESULTS: 35 patients were studied. Isolation and PCR results of the 13
      samples were negative in 12 of them and positive to denguevirus-3 in one of them.
      The determination of IgM was positive for dengue fever in 25 cases; 2 were
      positive to Mayaro virus and 8 were negative to what was looked for. Hemorrhages
      and thrombocytopenia were more frequent in patients infected with dengue and
      Mayaro viruses; jaundice and encephalopathy were more frequent in the latter, and
      renal dysfunction, in patients with a negative result. Evolution was satisfactory
      in all cases, except for one (Mayaro), which presented hemorrhages,
      thrombocytopenia, jaundice and encephalopathy that lead to death. CONCLUSIONS:
      The results show the risk of appearance and dissemination of several vector-born
      diseases in Mexico. Thus, they require intensive epidemiological surveillance to
      identify them and to know their real occurrence and specific clinical profile.

PMID- 16904039
TI  - [Presentation of a clinical case of systemic juvenile rheumatoid arthritis].
AB  - A case of a 6-year-old male child was studied. Initially, he presented large
      joint arthritis of the right knee and heel, with clinical data of systemic
      inflammation, such as fever, increase in sedimentation rate and leucocytosis,
      during more than six weeks of evolution. A wrong initial diagnosis of septic
      arthritis was made, but the lack of response to antibiotics and surgical drainage
      of the knee led to a trial with prednisone, which induced clinical remission. The
      patient remained hospitalized for 24 days and underwent surgical drainage, knee
      arthroscopy, two bone gammagrams, nuclear magnetic resonance, and antibiotics, as
      well as considerable stress and uncertainty for him and his family. Thus, it is
      very important to make an early diagnosis of juvenile rheumatoid arthritis and
      avoid complications. Recent literature was examined with special emphasis on
      opportune clinical diagnosis, as well as on therapeutic innovations, which have
      been able to modify the course of the disease and improve the quality of life of
      these patients. Pediatricians and general practitioners should take into account
      this diagnosis when seeing a patient with arthritis, especially when the signs
      point towards a systemic disease affecting two or more joints.

PMID- 16904040
TI  - [Cerebral venous thrombosis in systemic lupus erythematosus. Case report and
      literature review].
AB  - We reviewed a case of cerebral venous thrombosis as the manifestation of systemic
      lupus erythematosus in a 27-year-old woman whose main symptom was headache, and
      in which subarachnoid hemorrhage was initially suspected. The angiography
      revealed thrombosis in the superior longitudinal sinus. The treatment with
      steroids was satisfactory, with complete resolution of symptoms. We also reviewed
      the reported cases in medical literature.

PMID- 16904041
TI  - [Images of gastrointestinal endoscopy. Esophagic candidiasis].

PMID- 16904042
TI  - [Generic medicines. Second intervention].

PMID- 16904044
TI  - [IMSS in Numbers: the Census of Diabetic Patients, 2004].
AB  - The census of diabetic patients at the Instituto Mexicano del Seguro Social
      describes the state and level of control of biologic markers, such as glucose,
      BMI and blood pressure of all diabetic patients attending the family medicine
      units during 2004. The main results show that 2,334,340 diabetic patients visited
      the health units of the Instituto Mexicano del Seguro Social with an average of
      3.7 visits per year. Around 75% of the patients had their weight and height
      registered; 73%, their blood pressure, and only 28.8%, their glycemia level. One
      third of the patients (35.7%) had an unspecified diagnosis of diabetes mellitus
      and 91.3% had no complications reported. Of those with glycemia reported, 56.9%
      had a poor blood glucose control. Half of the diabetic patients were also
      diagnosed as hypertensive though 74% had good blood pressure control. The BMI
      reported that 40.4% were obese and 39.6% were overweight. All these data are
      important to measure the impact of different health interventions that point to a
      better control of diabetes at the IMSS.

PMID- 16904045
TI  - [Clinical effects of the alterations that emerge in the signaling mechanisms of
      the insulin receptor].
AB  - Phosphorilation of subunit beta from insulin receptor induced mainly by insulin,
      it begins a series of intracellular complex signaling in cascade. Through this
      way establish multiple effects, which permits to the cell initiate its biological
      activity. This activity include the glucose metabolism, the regulation of ions
      and amino acids transport, lipids metabolism, glycogen synthesis, genetic
      transcription, mRNA expression, synthesis and degradation of proteins, as well as
      synthesis of DNA. Therefore, a modification in anyone of the proteins involved in
      the insulin signaling, can take place a dysfunction in the glucose metabolism.
      The impaired glucose can be due because there are many proteins, ions and enzymes
      that participate in the downstream pathways of the insulin signaling, it has
      become difficult to find a single phatophysiologic level as cause of diabetes. In
      spite of the advances in the study of this disease, it has been reached the
      conclusion that the glucose control is not enough to impede the complications
      that characterize to type 2 diabetes, since the organic worsening does not stop,
      which indicates that insulin signaling dysfunction is directly involved in all
      cellular process, and a better understanding in the communication ways of this
      hormone will take to new forms of treatment to impaired insulin response.

PMID- 16904046
TI  - A review of the evidence on the effects and costs of implantable cardioverter
      defibrillator therapy in different patient groups, and modelling of cost
      effectiveness and cost-utility for these groups in a UK context.
AB  - OBJECTIVES: To update the systematic review evidence on the effectiveness, health
      related quality of life (HRQoL) and cost-effectiveness of implantable
      cardioverter defibrillators (ICDs); compilation of new data on the service
      provision in the UK; and on the clinical characteristics, survival, quality of
      life and costs of ICD patients in the UK, and a new cost-effectiveness model
      using both international RCT and UK-specific data. DATA SOURCES: Electronic
      databases searched from November 1999 to March 2003, this was supplemented by a
      systematic review of research published during 2003-5. Survey data. REVIEW
      METHODS: Studies were selected and assessed. A survey of ICD centres was carried
      out. Basic data were obtained from two major implanting centres including 535
      patients (approximately 10% of overall UK activity) implanted between 1991 and
      2002, and retrieval of fuller data, on patient characteristics, management and
      resource use, from patient notes for a sample of 426 patients was attempted. A
      cross-sectional survey collected HRQoL data (using the Nottingham Health Profile,
      Short Form 36, Hospital Anxiety and Depression questionnaire, EuroQoL 5
      Dimensions and disease-specific questions) on a sample of 229 patients. A Markov
      model combined UK patient data with data from published randomised controlled
      trials (RCTs) to estimate incremental costs per life-year or quality-adjusted
      life-year (QALY) gained. RESULTS: None of the economic analyses in the studies
      found could be directly applied to the UK. The multiple sources of routine data
      available (including the national ICD database) provide an imperfect picture of
      the need for and use of ICDs. Implantation rates have been rising to a rate of
      around 20 per million population. Mean age is increasing and most ICDs are
      implanted into men aged 45-74 years. There is significant geographical variation.
      A survey of 41 UK centres provided additional evidence, particularly of variation
      in level of activity and resourcing. Most detailed data were obtained for 380
      patients (89%). The postal survey produced a 73% response rate. Demographic
      characteristics of these patients were similar to ICD recipients in the UK as a
      whole and patients included in secondary prevention RCTs. Mean actuarial survival
      at 1, 3 and 5 years was 92%, 86% and 71%, respectively. Patient age at
      implantation and functional status significantly affected survival. Levels of
      most of the HRQoL measures were lower than for a UK general population. There was
      no evidence of a change with time from implantation. Patients who had suffered
      ICD shocks had significantly poorer HRQoL. Most patients nevertheless expressed a
      high level of satisfaction with ICD therapy. Mean initial costs of implantation
      showed little variation between centres (23,300 pounds versus 22,100 pounds) or
      between earlier and more recent implants. There appeared to be greater variation
      between patients presenting along different pathways. Postdischarge costs (tests,
      medications and follow-up consultations) and costs of additional hospitalisations
      were also calculated. Using the Markov model it was found that over a 20-year
      horizon, mean discounted incremental costs were 70,900 pounds (35,000-142,400
      pounds). Mean discounted gain was 1.24 years (0.29-2.32) or 0.93 QALYs. Cost
      effectiveness was most favourable for men aged over 70 years with a left
      ventricular ejection fraction (LVEF) below 35%. If the treatment effect were to
      continue, then the cost per life-year over a lifetime might fall to around 32,000
      pounds. Five RCTs of ICDs, a meta-analysis and, a cost-effectiveness analysis of
      ICDs used in primary prevention, and a meta-analysis of ICDs in patients with non
      ischaemic cardiomyopathy have been published recently. These trials provide
      confirmation of survival benefit of ICDs used in primary prevention in both
      ischaemic and non-ischaemic cardiomyopathy patients. Costs per QALY ranged from
      US$34,000 in older trials to controls being both less expensive and more
      effective (CABG Patch, DINAMIT). More recent trials estimated cost per QALY
      between $50,300 and $70,200. The inconsistency in evidence for a HRQoL benefit
      has not been resolved and further work on risk stratification is necessary.
      CONCLUSIONS: The evidence of short- to medium-term patient benefit from ICDs is
      strong but cost-effectiveness modelling indicates that the extent of that benefit
      is probably not sufficient to make the technology cost-effective as used
      currently in the UK. One reason is the high rates of postimplantation
      hospitalisation. Better patient targeting and efforts to reduce the need for such
      hospitalisation may improve cost-effectiveness. Further cost-effectiveness
      modelling, underpinned by an improved ICD database with reliable long-term follow
      up, is required. The absence of a robust measure of the incidence of sudden
      cardiac death is noted and this may be an area where further organisational
      changes with improved data collection would help.

PMID- 16904047
TI  - Adefovir dipivoxil and pegylated interferon alfa-2a for the treatment of chronic
      hepatitis B: a systematic review and economic evaluation.
AB  - OBJECTIVES: To assess the clinical effectiveness and cost-effectiveness of
      adefovirdipivoxil (ADV) and pegylated interferon alfa-2a (PEG) for the treatment
      of adults with chronic hepatitis B infection (CHB). DATA SOURCES: Electronic
      databases for the period from 1995-6 to April 2005. Websites of the relevant
      organisations. REVIEW METHODS: Searches were made for studies of clinical
      effectiveness, cost-effectiveness, quality of life, resource use/costs and
      epidemiology/natural history. Randomised controlled trials (RCTs) were included
      that compared PEG and ADV with currently licensed treatments for CHB, including
      non-pegylated ('standard') interferon alfa (IFN), lamivudine (LAM), and best
      supportive care. The trials were reviewed in a narrative synthesis but meta
      analysis was not undertaken owing to heterogeneity in the interventions and
      comparators evaluated. A model was developed to estimate the cost-effectiveness
      (cost-utility) of PEG and of ADV compared with IFN, LAM and best supportive care
      in a UK cohort of adults with CHB. The perspective of the cost-effectiveness
      analysis was that of the NHS and personal social services. A Markov state
      transition model was constructed, informed by a systematic search of the
      literature to identify source material on the natural history, epidemiology and
      treatment of CHB. Interventions were evaluated against their closest comparator
      (for PEG this is IFN, and for ADV this is LAM). In addition, the cost
      effectiveness of sequential treatment scenarios was modelled. RESULTS: A total of
      1086 references to clinical effectiveness studies were identified, of which seven
      fully published RCTs and one systematic review met the inclusion criteria. Four
      of the RCTs evaluated the effectiveness of ADV and three reported results for
      PEG. In addition, a conference abstract was included reporting interim results
      from an on-going Phase II RCT of ADV in combination with LAM. The published
      trials were of good quality, although details of randomisation and allocation of
      concealment were poorly reported. ADV was significantly more effective than
      placebo. Response rates were in the range 21-51% compared with 0%, respectively.
      For patients resistant to LAM, response rates were significantly higher for those
      treated with ADV in addition to on-going LAM (35-85%) than those who continued on
      LAM with placebo (0-11%). Significant alanine aminotransferase (ALT) reductions
      to normal levels were observed in all studies. For treatment-naive patients,
      seroconversion rates were 12-14% for ADV compared with 6% for placebo
      (statistically significant), rates were higher for LAM-resistant patients who
      received ADV in addition to on-going LAM (8%) than those who continued on LAM
      with placebo (2%) (no significance value was reported), and rates were higher for
      LAM-resistant patients who switched to ADV than those who continued on LAM with
      placebo (11 versus 0%, respectively; not statistically significant). HBsAg loss
      or seroconversion was observed in less than 5% of patients taking ADV. Two ADV
      studies reported changes in liver histology. In general, histological improvement
      and necroinflammatory activity/fibrosis scores were significantly better in ADV
      groups than in placebo groups. Dose discontinuations for safety reasons were low
      for patients receiving ADV. With the exception of headache, the most commonly
      reported adverse events were often seen in the placebo groups in similar
      proportions to the ADV groups, with different trials reporting conflicting
      results. PEG/LAM dual therapy and PEG monotherapy were similar in effect on HBV
      DNA and ALT levels, and both were significantly superior to LAM monotherapy.
      Response rates were higher for HBeAg-negative patients than for HBeAg-positive
      patients. HBeAg seroconversion rates at follow-up were significantly higher for
      PEG monotherapy patients than for those receiving either a combination of PEG and
      LAM or LAM monotherapy (32, 27 and 19%, respectively). For the comparison between
      PEG and IFN-2a, there was a significant difference in the combined outcome of ALT
      normalisation, HBV DNA response and HBeAg seroconversion at follow-up (24 versus
      12%, respectively). Changes in liver histology were reported by two studies.
      There was no statistically significant difference in histological improvement
      between the PEG monotherapy groups, the LAM monotherapy groups and the dual
      therapy groups. Two PEG trials reported small percentages (up to 5%) of HBsAg
      loss or seroconversion among patients receiving PEG either as monotherapy or in
      combination with LAM, but no HBsAg loss or seroconversion was reported in those
      receiving LAM monotherapy. Health-related quality of life (HRQoL) scores, as
      measured by the Short Form with 36 Items, decreased during treatment, but
      returned to at least baseline levels at follow-up (based on unpublished data).
      For HBeAg-positive patients, there were no significant differences in scores
      between treatment groups. Dose discontinuations for safety reasons were
      significantly higher for patients receiving PEG than for patients receiving LAM
      monotherapy. The most commonly reported adverse events in the PEG studies were
      headache, pyrexia, fatigue, myalgia and alopecia. Only one fully published
      economic evaluation was identified, reporting a US cost-effectiveness study of
      ADV as salvage therapy for chronic hepatitis B with LAM resistance. A Markov
      model was used to estimate cost-effectiveness of interferon alfa (6-12 months),
      LAM and LAM followed by ADV when resistance occurs. ADV generated the most
      (undiscounted) life-years, but at highest costs, with an incremental cost
      effectiveness ratio (ICER) of US$14,204 per life-year gained. Using our model,
      incremental cost per QALY estimates (baseline cohort of all patients) were: 5994
      pounds for IFN compared with best supportive care, 6119 pounds for PEG compared
      with IFN, 3685 pounds for LAM compared with best supportive care, and 16,569
      pounds for ADV compared with LAM. Incremental cost per QALY estimates (HBeAg
      positive patients only) were: 7936 pounds for IFN (24 weeks) compared with best
      supportive care, 16,166 pounds for PEG (48 weeks) compared with IFN (24 weeks),
      3489 pounds for LAM compared with best supportive care, and 15,289 pounds for ADV
      compared with LAM. Incremental cost per QALY estimates (HBeAg-negative patients
      only) were: 3922 pounds for IFN (48 weeks) compared with best supportive care,
      2162 pounds for PEG (48 weeks) compared with IFN (24 weeks), 4131 pounds for LAM
      compared with best supportive care, and 18,620 pounds for ADV compared with LAM.
      For the sequential treatment strategies, incremental cost per QALY estimates
      ranged from 3604 pounds (IFN followed by LAM versus IFN alone) to 11,402 pounds
      (IFN followed by LAM with adefovir salvage versus IFN followed by LAM). In all of
      these cases, the ICERs are well within the range that would conventionally be
      regarded as being cost-effective. The probabilistic sensitivity analysis found
      that LAM is a cost-effective option at lower willingness-to-pay thresholds for
      health outcomes, but as the threshold is increased adefovir is increasingly
      likely to be the optimal intervention. Where a willingness-to-pay threshold of
      above 10,000 pounds per QALY is employed, PEG is highly likely to be the optimal
      intervention compared with IFN (based on a cohort of HBeAg-positive and -negative
      patients). Interferon alfa (non-pegylated or pegylated) followed by LAM would be
      the optimal strategy at lower willingness-to-pay thresholds. As the threshold
      increases, the sequential treatment strategy of PEG followed by LAM with adefovir
      added as salvage therapy is increasingly likely to be the optimal intervention.
      CONCLUSIONS: ADV and PEG are associated with significant improvements in a number
      of biochemical, virological and histological outcomes in both HBeAg-positive and 
      negative patients. For a small proportion of patients this is associated with
      resolution of infection. For another proportion it leads to remission and a
      reduced risk of progressing to cirrhosis, hepatocellular carcinoma, liver
      transplant and death. For others who do not respond or who relapse, retreatment
      with another agent is necessary. The results of our cost-effectiveness analysis
      demonstrate that incremental costs per QALY for a range of comparisons were
      between 5994 pounds and 16,569 pounds and within the range considered by NHS
      decision-makers to represent good value for money. When subjected to sensitivity
      analysis, most costs per QALY estimates remained under 30,000 pounds. Further RCT
      evidence of the effectiveness of anti-viral treatment is required, particularly
      for subgroups of patients with different genotypes, patients with cirrhosis,
      patients from different ethnic groups, patients with co-infections (e.g. HIV,
      HCV) and co-morbidities, liver transplant patients and children and adolescents.

PMID- 16904048
TI  - An evaluation of the clinical and cost-effectiveness of pulmonary artery
      catheters in patient management in intensive care: a systematic review and a
      randomised controlled trial.
AB  - OBJECTIVES: To evaluate the clinical and cost-effectiveness of managing
      critically ill patients in adult, general intensive care with or without
      pulmonary artery catheters (PACs). DESIGN: An open, multi-centre, randomised
      controlled trial with economic evaluation (cost-utility and cost-effectiveness
      analysis). SETTING: The setting was general (mixed medical/surgical) intensive
      care units (ICUs) in the UK admitting adults. PARTICIPANTS: Adult patients in
      participating ICUs deemed by the responsible treating clinician to require
      management with a PAC. INTERVENTIONS: These were insertion of a PAC and
      subsequent clinical management, at the discretion of the responsible treating
      clinicians, using data derived from the PAC. The control group were managed
      without a PAC but with the option of using alternative cardiac output monitoring
      devices. MAIN OUTCOME MEASURES: The main outcome measure was hospital mortality.
      Secondary outcome measures were length of stay in the ICU, length of stay in an
      acute hospital and organ-days of support in the ICU. For the economic evaluation,
      the main outcome measure was quality-adjusted life-years (QALYs) and the
      secondary outcome measure was hospital mortality. RESULTS: Sixty-five ICUs in the
      UK participated. Of these, 43 (66%) used alternative cardiac output monitoring
      devices in control group patients. A total of 1263 patients were identified as
      being eligible for the trial. Of these, 1041 (82.4%) were randomised and
      allocated to management with (n = 519) or without (n = 522) a PAC. There were no
      losses to follow-up. However, 27 patients (13 in the PAC group and 14 in the
      control group) were withdrawn from the trial because either the patient withdrew
      consent on recovering mental competency or the relatives withdrew agreement
      following randomisation. Data on 1014 patients were included in the analysis.
      Participants in the two groups had similar baseline characteristics. There was no
      difference in hospital mortality for patients managed with (68.4%) or without
      (65.7%) a PAC. The adjusted hazard ratio (PAC versus no PAC) was 1.09 [95%
      confidence interval (CI) 0.94 to 1.27]. There was no difference in the median
      length of stay in ICU, the median length of stay in an acute hospital or mean
      organ-days of support in ICU between the two groups. The economic evaluation
      found that the expected cost per QALY gained from the withdrawal of PAC was 2985
      pounds. The expected cost per life gained from the withdrawal of PAC was 22,038
      pounds. CONCLUSIONS: Clinical management of critically ill patients with a PAC,
      as currently practised in the UK, neither improves hospital survival for adult,
      general intensive care patients nor reduces length of stay in hospital. The lack
      of demonstrable benefit from a device previously believed to be beneficial could
      be explained by statistical chance, by misinterpretation of PAC-derived data, by
      ineffective treatment strategies based on data correctly interpreted using the
      current paradigm or by subsequent inaction following insertion of the device. It
      is also possible that detailed data on haemodynamics, however used, cannot modify
      the disease process sufficiently to influence disease outcome. The economic
      evaluation, using decision analysis techniques rather than conventional
      hypothesis testing, suggests that the withdrawal of the PAC from routine clinical
      practice in the NHS would be considered cost-effective in the current decision
      making climate, and might result in lives or life-years being saved at modest
      cost. With the declining use of PACs in the UK and the findings of this report
      indicating no overall benefit from management with a PAC, it should now be
      possible to examine protocolised management with a PAC in selected groups of
      critically ill patients against appropriate controls, something that was
      difficult while PACs were the considered standard of care.

PMID- 16904049
TI  - Accurate, practical and cost-effective assessment of carotid stenosis in the UK.
AB  - OBJECTIVES: To determine whether less invasive imaging tests [ultrasound (US),
      magnetic resonance angiography (MRA), computed tomographic angiography (CTA) and
      contrast-enhanced MRA (CEMRA)], alone or combined, could replace intra-arterial
      angiography (IAA), what effect this would have on strokes and deaths,
      endarterectomies performed and costs, and whether less invasive tests were cost
      effective. DATA SOURCES: Electronic databases covering the years 1980-2003
      inclusive, updated to April 2004. Key journals from 1990 to the end of 2002.
      REVIEW METHODS: The authors constituted a panel of experts in stroke, imaging,
      vascular surgery, statistics and health economic modelling. The accuracy of less
      invasive carotid imaging was systematically reviewed using Standards for
      Reporting of Diagnostic Accuracy (STARD) methodology, supplemented by individual
      patient data from UK primary research and audit studies. A systematic review of
      the costs of less invasive tests, outpatient clinics, endarterectomy and stroke
      was performed, along with a microcosting exercise. A model of the process of care
      following a transient ischaemic attack (TIA)/minor stroke was developed,
      populated with data from stroke epidemiology studies in the UK, effects of
      medical and surgical interventions, outcomes, quality of life and costs. A survey
      of UK stroke prevention clinics provided typical timings. Twenty-two different
      carotid imaging strategies were evaluated for short- and long-term outcomes,
      quality-adjusted life-years (QALYs) and net benefit. RESULTS: In 41 included
      studies (2404 patients, median age 60-65 years), most data were available on 70
      99% stenosis. CEMRA was the most accurate [sensitivity 0.94, 95% confidence
      interval (CI) 0.88 to 0.97; specificity 0.93, 95% CI 0.89 to 0.96], compared with
      US, MRA and CTA, which were all similar (e.g. for US: sensitivity 0.89, 95% CI
      0.85 to 0.92; specificity 0.84, 95% CI 0.77 to 0.89). Data for 50-69% stenoses
      and on combinations of tests were too sparse to be reliable. There was
      heterogeneity between studies for all imaging modalities except for CTA. The
      individual patient data (2416 patients) showed that the literature overestimated
      test accuracy in routine practice and that, in general, tests perform with higher
      sensitivity and specificity in asymptomatic than in symptomatic arteries. In the
      cost-effectiveness model, on current UK timings, strategies allowed more patients
      to reach endarterectomy very quickly, and where those with 50-69% stenosis would
      be offered surgery in addition to those with 70-99%, prevented most strokes and
      produced greatest net benefit. This included most strategies with US as first or
      repeat test, and not those with IAA. However, the model was sensitive to less
      invasive test accuracy, cost and timing of endarterectomy. In patients
      investigated late after TIA, test accuracy is crucial and CEMRA should be used
      before surgery. CONCLUSIONS: In the UK, less invasive tests can be used in place
      of IAA if radiologists trained in carotid imaging are available. Imaging should
      be carefully audited. Stroke prevention clinics should reduce waiting times at
      all stages to improve speed of access to endarterectomy. In patients presenting
      late after TIA, test accuracy is very important and US results should be
      confirmed by CEMRA, as patients with 50-69% stenosis are less likely to benefit.
      More data are required to define the accuracy of the less invasive tests, with
      improvements made in the data collection methods used and how data are presented.
      Consideration should also be given to the use of new technologies and randomised
      trials.

PMID- 16904050
TI  - Prostate-specific antigen and detection of prostate cancer: What have we learned
      and what should we recommend for screening?
AB  - Prostate-specific antigen (PSA) has become one of the most commonly used cancer
      clinical tests, and routine PSA-based screening has led to a dramatic increase in
      prostate cancer detection. A significant downward stage migration has resulted,
      and a decrease in prostate cancer mortality has also been observed. However, PSA
      screening remains controversial because there is no definitive proof that it
      decreases prostate cancer death rates, and there is concern that it may detect a
      significant number of clinically insignificant cancers. Screening age and
      interval have been recently questioned, and the best threshold to recommend
      biopsy has been complicated by new data showing that prostate cancer exists at
      all PSA levels, even those thought to be "normal" in the past. It is hoped that
      ongoing prospective screening trials will determine the value of PSA screening.
      However, until these results are available the controversy will continue, and men
      will continue to be screened.

PMID- 16904051
TI  - Should finasteride be used to prevent prostate cancer?
AB  - Prostate cancer is an important public health problem. Chemoprevention offers an
      attractive solution because it may lead to decreased disease-specific mortality.
      Furthermore, because many men are treated radically for prostate cancers that
      pose little or no threat to life, chemoprevention may also provide an excellent
      strategy for diminishing treatment-related costs and adverse effects such as
      erectile and urinary dysfunction. The Prostate Cancer Prevention Trial was a 7
      year randomized study of finasteride versus placebo among men aged older than 55
      years. All men were intended to have a prostate biopsy at study conclusion. At
      trial's end, there was a 25% reduction in period prevalence in all prostate
      cancers (24.4% for placebo vs 18.4% for finasteride). This represents a 6%
      absolute risk reduction. A larger number of higher-grade cancers were noted among
      men randomized to finasteride, which post hoc analyses and studies suggest are
      almost certainly related to previously unrecognized biases in trial design. There
      continues to be great debate as to the clinical significance of the cancers
      prevented. It is our opinion that among men who warrant 5-alpha reductase
      inhibitors (5ARIs) as part of their benign prostatic hyperplasia regimen, cancer
      prevention should be recognized as an additional benefit of treatment.
      Furthermore, men with high risk of clinically significant prostate cancer, such
      as significant family history, abnormal prostate biopsy histologies, and African
      descent, should be made aware of these findings. Men with significant anxiety or
      concern about prostate cancer should also be made aware of the risks and benefits
      of this therapy. Additional trials of antiestrogens, micronutrients, and other
      5ARIs, which will mature over the next 2 to 5 years, will better define the role
      of 5ARIs in prostate cancer chemoprevention.

PMID- 16904052
TI  - Active surveillance versus radical treatment for favorable-risk localized
      prostate cancer.
AB  - Widespread prostate-specific antigen (PSA) screening in North America has
      resulted in a profound stage migration and a marked increase in incidence. One in
      six men is now diagnosed, many with small-volume, low-grade cancer. This
      incidence is dramatically higher than the 3% lifetime risk of prostate cancer
      death that characterized the pre-screening era. This article summarizes the case
      for active surveillance for "favorable-risk" prostate cancer with selective
      delayed intervention for rapid biochemical progression, assessed by increasing
      PSA levels, or grade progression. The results of a large phase II trial using
      this approach are reviewed. To date, this study has shown that virtually all men
      with favorable-risk prostate cancer managed in this fashion will die of unrelated
      causes. Based on the Swedish randomized trial of radical prostatectomy versus
      watchful waiting, the Connecticut observation series, and the Toronto active
      surveillance experience, a number needed to treat analysis of the benefit of
      radical treatment of all newly diagnosed favorable-risk prostate cancer patients,
      compared with a strategy of active surveillance with selective delayed
      intervention, is presented. This suggests that approximately 73 patients will
      require radical treatment for each prostate cancer death averted. This translates
      into a 3- to 4-week survival benefit, unadjusted for quality of life. This figure
      is confirmed based on an analysis of the 2004 D'Amico et al. PSA velocity data in
      favorable-risk disease. The approach of active surveillance with selective
      delayed intervention based on PSA doubling time and repeat biopsy represents a
      practical compromise between radical therapy for all patients (which results in
      overtreatment for patients with indolent disease) and watchful waiting with
      palliative therapy only (which results in undertreatment for those with
      aggressive disease).

PMID- 16904053
TI  - Testosterone therapy for men at risk for or with history of prostate cancer.
AB  - Since the early 1940s when Huggins showed that severe reductions in serum
      testosterone by castration or estrogen therapy caused regression of prostate
      cancer (PCa), it has been assumed that higher testosterone levels cause enhanced
      growth of PCa. For this reason, it has been considered taboo to offer
      testosterone replacement therapy (TRT) to any man with a prior history of PCa,
      even if all objective evidence suggests he has been cured. The fear has been that
      higher testosterone levels would "awaken" dormant cells and cause a recurrence.
      Thus, US Food and Drug Administration-mandated language in all testosterone
      package inserts states that testosterone is contraindicated in men with a history
      of, or suspected of having, PCa. Although there is little modern experience with
      administration of testosterone in men with known history of PCa, there is a
      varied and extensive literature indicating that TRT does not pose any increased
      risk of PCa growth in men with or without prior treatment. For instance, the
      cancer rate in TRT trials is only approximately 1%, similar to detection rates in
      screening programs, yet biopsy-detectable PCa is found in one of seven
      hypogonadal men. Moreover, PCa is almost never seen in the peak testosterone
      years of the early 20s, despite autopsy evidence that men in this age group
      already harbor microfoci of PCa in substantial numbers. The growing number of PCa
      survivors who happen to be hypogonadal and request treatment has spurred a change
      in attitude toward this topic, with increasing numbers of physicians now offering
      TRT to men who appear cured of their disease. Publications have now reported no
      prostate-specific antigen (PSA) recurrence with TRT in small numbers of men who
      had undetectable PSA values after radical prostatectomy. Although still
      controversial, there appears to be little reason to withhold TRT from men with
      favorable outcomes after definitive treatment for PCa. Monitoring with PSA and
      digital rectal examination at regular intervals is recommended.

PMID- 16904055
TI  - Adjuvant and neoadjuvant approaches to treat surgically resectable pancreatic
      cancer.
AB  - Adjuvant therapy for pancreatic cancer is currently a controversial topic. Very
      little is known about the potential components of adjuvant therapy. All published
      randomized trials evaluating adjuvant therapy for pancreatic cancer have
      limitations that prevent the establishment of an absolute "standard of care."
      However, with the recent report of Charite Onkologie Clinical Studies in
      Gastrointestinal Cancer in abstract form and European Study Group for Pancreatic
      Cancer-1, it is clear that chemotherapy has an effect as adjuvant therapy. The
      role of radiation remains unclear. The future of adjuvant therapy is dependent on
      the investigators designing better trials that answer the important remaining
      questions: the role of radiation therapy, the integration of newer agents, and
      the best regimen of those currently available.

PMID- 16904054
TI  - Cytotoxic chemotherapy for prostate cancer: Who and when?
AB  - The survival benefit demonstrated by docetaxel-based therapy in two randomized
      trials, Southwest Oncology Group (SWOG) 99-16 and TAX 327, has changed the
      perception of chemotherapy in men with hormone-refractory prostate cancer from
      nihilism to optimism. These survival improvements are of similar magnitude to
      those found in trials that established chemotherapeutic regimens for metastatic
      breast, lung, or colorectal cancer. The timing of chemotherapy in the
      aforementioned solid tumors is much more clearly defined than in men with
      metastatic prostate cancer. Traditionally, chemotherapy in men with hormone
      resistant prostate cancer was reserved for symptomatic patients only; the
      inclusion of symptomatic and asymptomatic patients in SWOG 99-16 and TAX 327 has
      raised several questions regarding the optimal use of chemotherapy in these
      patients. When is the best time to initiate docetaxel-based chemotherapy? Is it
      appropriate to use chemotherapy in high-risk patients as adjuvant therapy?
      Although retrospective analysis of current trials may provide hypothesis, only
      properly designed randomized clinical trials will answer these questions.

PMID- 16904056
TI  - Metastatic colorectal cancer: Therapeutic options.
AB  - For the past several decades, the therapy for metastatic colorectal cancer had
      modest benefits because of the limited therapeutic options. Bolus 5-fluorouracil
      (5FU) and leucovorin (LV) were the standard of care in the United States until
      2002, with a response rate of 25% and a median survival of 10 to 12 months.
      However, with the advent of new agents, namely oxaliplatin and irinotecan, there
      has been a dramatic change in the way we treat metastatic colorectal cancer.
      Based on many well-conducted large randomized trials, we have evidence that
      combination chemotherapy incorporating oxaliplatin or irinotecan with infusional
      5FU/LV is superior to 5FU/LV, with doubling of overall survival (OS) to
      approximately 20 months. There remains some uncertainty as to the best first-line
      regimen. This might be irrelevant because studies have shown that OS is dependent
      on exposure to all the active agents, regardless of the time period of exposure.
      Bevacizumab, which uses anti-angiogenic strategies, has improved disease-free
      survival (DFS) and OS when combined with standard chemotherapy and is a vital
      component of metastatic colorectal cancer therapy. However, there are no data
      supporting its use past progression. Cetuximab, an epithelial growth factor
      receptor inhibitor, is mainly used in irinotecan-refractory patients. In spite of
      all these advances, 5-year OS rates continue to be limited. Patients with
      curative resection of metastatic disease seem to have longer DFS and better 5
      year OS rates. This should be a potential goal for responding patients with
      upfront unresectable, organ-limited disease.

PMID- 16904057
TI  - Liver-directed therapies for patients with primary liver cancer and hepatic
      metastases.
AB  - Liver cancer, whether primary or metastatic, is a major cause of death throughout
      the world. The surgical management of these diseases varies according to the
      extent of disease and the overall health of the patient. Surgical resection of
      hepatic disease remains the only chance for cure. However, a large proportion of
      patients with liver cancer are unable to undergo a complete surgical resection.
      These patients are often treated with liver-directed therapies. Although not as
      effective as surgical resection, these approaches can help to improve the
      survival of patients. In patients with primary liver cancer, underlying liver
      disease often prohibits surgical intervention. However, survival advantages have
      been gained with the application of percutaneous alcohol injection and
      radiofrequency ablation (RFA). In patients with hepatic metastases, the number of
      metastases is often what prevents surgical resection. In these patients, RFA,
      cryoablation, and hepatic artery infusional therapy have all aided in prolonging
      survival. As chemotherapeutic agents improve and targeted therapies are
      developed, more patients will be able to undergo surgical management of their
      liver cancer, primary or metastatic.

PMID- 16904059
TI  - Forecasting from ignorance: the use and usefulness of recognition in lay
      predictions of sports events.
AB  - Whereas previous studies on how people make forecasts of sports events focused
      primarily on experts, we examined how laypeople do this task. In particular, we
      (a) tested the recognition heuristic [Goldstein, D. G., & Gigerenzer, G. (2002).
      Models of ecological rationality: the recognition heuristic. Psychological
      Review, 109, 75-90], which requires partial ignorance, against four alternative
      mechanisms in describing laypeople's forecasts for the European Soccer
      Championships 2004; (b) evaluated how well recognition predicted the outcomes of
      the matches compared to direct indicators of team strength (e.g., past
      performance, rankings); and (c) studied the less-is-more effect--the phenomenon
      that knowing less leads to more correct forecasts than knowing more--which can
      occur when the recognition heuristic is used. Two groups of participants
      (laypeople, experts) made forecasts for the first-round matches of the
      tournament. Of the five candidate mechanisms, the recognition heuristic predicted
      laypeople's forecasts best: when applicable, it accounted for 90% of the
      forecasts. The recognition heuristic correctly predicted the actual winner of the
      matches substantially better than chance but did not achieve the accuracy of
      direct indicators of team strength. The experts made more correct forecasts than
      the laypeople. Moreover, we found no benefit of ignorance among the group of
      laypeople, although the conditions for a less-is-more effect specified by
      Goldstein and Gigerenzer were fulfilled.

PMID- 16904058
TI  - Cancer of the gastroesophageal junction: Current therapy options.
AB  - Active chemotherapy agents in metastatic adenocarcinoma of the esophagus include
      taxanes (docetaxel or paclitaxel), 5-fluorouracil, irinotecan, platinum drugs
      (including cisplatin, oxaliplatin, and carboplatin), and anthracyclines.
      Conventional chemotherapy combines infusional 5-fluorouracil with cisplatin. The
      addition of a third drug to this backbone results in greater toxicity and only
      marginal improvements in outcome. Alternative and potentially better-tolerated
      chemotherapy involves two-drug regimens, combining 5-fluorouracil with a taxane
      or irinotecan, or combining a platinum drug with irinotecan or a taxane. Although
      preoperative chemotherapy improves survival compared with surgery alone, the
      addition of radiation therapy to chemotherapy preoperatively improves rates of
      curative resection, reduces local tumor recurrence, and achieves a significant
      rate of pathologic complete response. Combined preoperative chemotherapy and
      concurrent radiotherapy is the preferred preoperative strategy for locally
      advanced adenocarcinoma of the esophagus. Survival is improved with postoperative
      chemotherapy and radiotherapy if none has been delivered preoperatively.

PMID- 16904061
TI  - Surface activity coefficients of spread monolayers of behenic acid salts at air
      water interface.
AB  - The pressure-area isotherms of ionized monolayers of behenic acid at air-water
      interface at pH 12.0 have been obtained from the Langmuir film balance
      experiments under various physico-chemical conditions. The value of the measured
      surface pressure at a given area per molecule is equal to the sum of the ideal
      pressure, cohesive pressure and electrical pressure. The electrical pressure term
      is regarded as the sum of the pressure originating from the Gouy-Chapman double
      layer including discrete ion effect, ion binding and monolayer hydration effect.
      At a given area, the deviation of the measured surface pressure from its ideal
      value has been calculated in terms of the apparent surface compressibility
      coefficients, surface fugacity coefficients for gaseous monolayer and surface
      activity coefficients of solute forming two-dimensional solutions in the
      monolayer phase respectively. Values of all these coefficients have been
      calculated for different compositions of the monolayer using non-ideal gas model
      and Raoult's and Henry's laws modified for two-dimensional non-ideal solutions
      respectively. Values of these coefficients may be higher or lower than unity
      depending upon ionic strengths and nature of inorganic salts present in the sub
      phase. Using these values of surface activity coefficients, the standard free
      energies of formation, of spread monolayers of salts of behenic acid have been
      calculated at different standard states of reference.

PMID- 16904062
TI  - The mitochondrial citrate transport protein: evidence for a steric interaction
      between glutamine 182 and leucine 120 and its relationship to the substrate
      translocation pathway and identification of other mechanistically essential
      residues.
AB  - Previous examination of the accessibility of a panel of single-Cys mutants in
      transmembrane domain III (TMDIII) of the yeast mitochondrial citrate transport
      protein to the hydrophilic, cysteine-specific methanethiosulfonate reagent MTSES
      enabled identification of the water-accessible surface of this TMD. Further
      studies on the effect of citrate on MTS reagent accessibility, indicated eight
      sites within TMD III at which citrate conferred temperature-independent
      protection, thus providing strong evidence for participation of these residues in
      the formation of a portion of the substrate translocation pathway. Unexpectedly,
      citrate did not protect against inhibition of the Leu120Cys variant, despite its
      location on a water- and citrate-accessible surface of the TMDIII helix. This led
      to the hypothesis that in the 3-dimensional CTP structure, TMDIV packs against
      TMDIII in a manner such that the Leu120 side-chain folds behind the side-chain of
      Gln182. The present investigations addressed this hypothesis by examining the
      properties of the Gln182Cys single mutant and the Leu120Cys/Gln182Ala double
      mutant. We observed that in contrast to our findings with the Leu120Cys mutant,
      citrate did protect the Gln182Cys variant against MTSES-mediated inhibition.
      Importantly, truncation of the Gln182 side-chain to Ala enabled citrate to
      protect the Leu120Cys double mutant against inhibition. In combination these data
      support the idea that the Gln182 side-chain lines the transport path and
      sterically blocks access of citrate to the Leu120 side-chain. In a parallel
      series of investigations, we constructed 24 single-Cys substitution mutants that
      were chosen based on their hypothesized importance in substrate binding and/or
      translocation. We observed that substitution of Cys for residues E34, K37, K83,
      R87, Y148, D236, K239, T240, R276, and R279 resulted in > or =98% inactivation of
      CTP function, suggesting an essential structural and/or mechanistic role for
      these native residues. Superposition of this functional data onto a detailed 3
      dimensional homology model of the CTP structure indicates that the side-chains of
      each of these residues project into the putative transport pathway. We
      hypothesize that a subset of these residues, in combination with four previously
      identified essential residues, define the citrate binding site(s) within the CTP.

PMID- 16904063
TI  - Dyadic predictors of outcome in a cognitive-behavioral program for patients with
      generalized anxiety disorder in committed relationships: a "spoonful of sugar"
      and a dose of non-hostile criticism may help.
AB  - The present study tested whether pre-treatment levels of partner hostility and
      non-hostile criticism predicted outcome in an individual cognitive-behavioral
      therapy package for generalized anxiety disorder (GAD). Eighteen patients with a
      principal or co-principal diagnosis of GAD were randomly allocated to a treatment
      condition (n=8) or a delayed treatment condition (n=10). In addition, the
      patients and their partners were videotaped discussing the patients' worries.
      These videotapes were later coded for levels of partner hostility and non-hostile
      criticism directed at the patients. Treatment resulted in statistically and
      clinically significant change at post-test. Finally, partner hostility predicted
      worse end-state functioning whereas partner non-hostile criticism predicted
      better end-state functioning.

PMID- 16904064
TI  - Comprehensive comparisons of the current human, mouse, and rat RefSeq, Ensembl,
      EST, and FANTOM3 datasets: identification of new human genes with specific tissue
      expression profile.
AB  - Our understanding of functional genetic elements in the genomes is continuously
      growing and new entries are entered in various databases on a regular basis. We
      have here merged the genetic elements in RefSeq, Ensembl, FANTOM3, HINV, and
      NCBI:s ESTdb using the genome assemblies in order to achieve a comprehensive
      picture of the current status of the identity and gene number in human, mouse,
      and rat. The number of human protein coding genes has not increased (25,043)
      while the increased sequencing of mouse transcripts has provided the considerably
      higher number of protein coding genes (31,578) in mouse. The results indicate
      large discrepancies between the datasets, as considerable numbers of unique
      transcripts can be found in each dataset. Despite the high number of ncRNA
      (38,129 in mouse) there are also almost 20,000 EST clusters in both mouse and
      humans with more than one EST that do not overlap any transcript suggesting that
      several new genetic elements are still to be found. We also demonstrated presence
      of new genes by identifying new human ones that have specific tissue profiles,
      using RT-PCR on rat tissues.

PMID- 16904065
TI  - Purinergic receptors involved in the immunomodulatory effects of ATP in human
      blood.
AB  - We recently showed that the physiological compound ATP simultaneously inhibited
      TNF-alpha and stimulated IL-10 release in LPS-PHA stimulated blood. The purpose
      of the present study was to determine the mechanism involved in the concerted
      modulatory effect of ATP on TNF-alpha and IL-10. Incubation of blood with ATP in
      the presence of selective P2 receptor antagonists showed that the stimulatory
      effect of ATP on IL-10 release was completely annihilated by both 2-MeSAMP (a
      P2Y12/13 receptor antagonist) and PSB-0413 (a P2Y12 receptor antagonist). On the
      other hand, the inhibitory effect of ATP on TNF-alpha release was completely
      reversed by 5'-AMPS (a P2Y11 receptor antagonist) as well as by H-89, an
      inhibitor of cAMP-activated PKA. The concerted inhibition by ATP of TNF-alpha
      release via P2Y11 activation and stimulation of IL-10 release via P2Y12
      activation implicates a novel approach towards immunomodulation by altering the
      balance among pro- and anti-inflammatory cytokines.

PMID- 16904066
TI  - An essential GT motif in the lamin A promoter mediates activation by CREB-binding
      protein.
AB  - Lamin A is an important component of nuclear architecture in mammalian cells.
      Mutations in the human lamin A gene lead to highly degenerative disorders that
      affect specific tissues. In studies directed towards understanding the mode of
      regulation of the lamin A promoter, we have identified an essential GT motif at 
      55 position by reporter gene assays and mutational analysis. Binding of this
      sequence to Sp transcription factors has been observed in electrophoretic
      mobility shift assays and by chromatin immunoprecipitation studies. Further
      functional analysis by co-expression of recombinant proteins and ChIP assays has
      shown an important regulatory role for CREB-binding protein in promoter
      activation, which is mediated by the GT motif.

PMID- 16904067
TI  - Osteocytes subjected to pulsating fluid flow regulate osteoblast proliferation
      and differentiation.
AB  - Osteocytes are thought to orchestrate bone remodeling, but it is unclear exactly
      how osteocytes influence neighboring bone cells. Here, we tested whether
      osteocytes, osteoblasts, and periosteal fibroblasts subjected to pulsating fluid
      flow (PFF) produce soluble factors that modulate the proliferation and
      differentiation of cultured osteoblasts and periosteal fibroblasts. We found that
      osteocyte PFF conditioned medium (CM) inhibited bone cell proliferation, and
      osteocytes produced the strongest inhibition of proliferation compared to
      osteoblasts and periosteal fibroblasts. The nitric oxide (NO) synthase inhibitor
      N(G)-nitro-L-arginine methyl ester (L-NAME) attenuated the inhibitory effects of
      osteocyte PFF CM, suggesting that a change in NO release is at least partially
      responsible for the inhibitory effects of osteocyte PFF CM. Furthermore,
      osteocyte PFF CM stimulated osteoblast differentiation measured as increased
      alkaline phosphatase activity, and l-NAME decreased the stimulatory effects of
      osteocyte PFF CM on osteoblast differentiation. We conclude that osteocytes
      subjected to PFF inhibit proliferation but stimulate differentiation of
      osteoblasts in vitro via soluble factors and that the release of these soluble
      factors was at least partially dependent on the activation of a NO pathway in
      osteocytes in response to PFF. Thus, the osteocyte appears to be more responsive
      to PFF than the osteoblast or periosteal fibroblast with respect to the
      production of soluble signaling molecules affecting osteoblast proliferation and
      differentiation.

PMID- 16904068
TI  - Effects of fibulin-5 on attachment, adhesion, and proliferation of primary human
      endothelial cells.
AB  - BACKGROUND: Fibulin-5 is a novel extracellular protein that is thought to act as
      a bridging peptide between elastin fibers and cell surface integrins in blood
      vessel wall. Fibulin-5 binding to endothelial cell (EC) surface integrins may
      effect cell proliferation and cell attachment to extracellular matrix (ECM) or to
      artificial surfaces. In this paper, we describe the effects of fibulin-5 on
      attachment, adhesion, and proliferation of primary human EC. After demonstrating
      that fibulin-5 over-expression inhibited EC proliferation, we tested the
      hypothesis that co-expression of fibulin-5 and VEGF165 will lead to unique EC
      phenotype that will exhibit increased adherence properties and retain its
      proliferation capacity. METHODS AND RESULTS: Fibulin-5 and VEGF165 gene transfer
      to primary human saphenous vein endothelial cells was accomplished using
      retroviral vectors encoding the two genes. Transgene expression was verified
      using immunohistochemistry, Western blotting, and ELISA. Fibulin 5 over
      expression tended to improve immediate EC attachment (30 min after seeding) and
      improved significantly adhesion (>40%) under shear stress tested 24h after EC
      seeding. The effects of fibulin-5 and VEGF165 on EC proliferation in the presence
      or absence of basic FGF were also tested. EC expressing fibulin-5 had reduced
      proliferation while VEGF165 co-expression ameliorated this effect. CONCLUSION:
      Fibulin-5 improved EC attachment to artificial surfaces. Dual transfer of fibulin
      5 and VEGF165 resulted in EC phenotype with increased adhesion and improved
      proliferation. This unique EC phenotype can be useful for tissue engineering on
      endovascular prostheses.

PMID- 16904069
TI  - Histone acetyltransferase p300 regulates the transcription of human erythroid
      specific 5-aminolevulinate synthase gene.
AB  - Erythroid-specific 5-aminolevulinate synthase (ALAS2) catalyzes the rate-limiting
      step in heme biosynthesis of erythroid cells. Here, we show that treatment of
      erythroid K562 cells with HDAC inhibitors sodium butyrate or Trichostatin A gave
      rise to a significant increase in ALAS2 gene transcripts, with a concurrent
      increase in acetylation level of histone H4 at the ALAS2 gene promoter. Histone
      acetyltransferase p300 bound withALAS2 promoter and overexpression of p300
      increased both the promoter reporter expression and endogenous mRNA level of
      ALAS2. Additionally, two functional Sp1 sites located in ALAS2 promoter were
      identified. Both of the GATA-1 sites and all the Sp1 sites at the ALAS2 promoter
      contributed to the transcription synergistic action with p300. These data
      implicated a close relationship between the acetylation modification of histone
      at the ALAS2 promoter and the regulation of this gene. Meanwhile, this work
      identified that ALAS2 is a novel target gene for p300/CBP action as histone
      acetyltransferases.

PMID- 16904070
TI  - SHP-2-Erk signaling regulates concanavalin A-dependent production of TIMP-2.
AB  - To search for the signaling critical for the production of tissue inhibitor of
      metalloproteinase-2 (TIMP-2), we investigated the role of SHP-2 in TIMP-2
      production with Concanavalin A (Con A)-treated cells. In wild-type fibroblasts,
      Con A-treatment dramatically activated TIMP-2 production. In contrast, production
      of TIMP-2 in response to Con A-treatment was severely impaired in cells
      expressing mutant SHP-2 whose 65 amino acids in the SH2-N domain were deleted.
      Con A-treatment activated dual signaling pathways, Erk and p38, in a SHP-2
      dependent manner. Pretreatment of wild-type cells with U0126, a potent inhibitor
      of MEK1, significantly inhibited the production of TIMP-2, whereas SB203580, a
      specific inhibitor for p38, could not. Finally, expression of exogenous wild-type
      SHP-2 in SHP-2 mutant cells clearly rescued Erk activation and TIMP-2 production
      in response to Con A-treatment. Taken together, our results strongly suggest that
      SHP-2 plays a critical role as a positive modulator for the production of TIMP-2
      via MEK1-Erk signaling in fibroblasts.

PMID- 16904071
TI  - Crucial role of position 40 for interactions of CCK-58 revealed by sequence of
      cat CCK-58.
AB  - Evidence suggests that amino terminal extensions of CCK-8 affect the carboxyl
      terminal bioactive region of CCK. Cat CCK-58 was purified by low pressure reverse
      phase and ion-exchange chromatography steps and several reverse phase HPLC steps.
      The purified peptide and its tryptic fragments were characterized by mass
      spectral analysis and microsequence analysis. The structure of cat CCK-58 is:
      AVQKVDGEPRAHLGALLARYIQQARKAPSGRMSVIKNLQSLDPSHRISDRDY(SO3) MGWMDF-amide. Cat and
      dog CCK-58 are identical except for position 40 which is serine in cat and
      asparagine in dog. Radioimmunoassay detected cat CCK-58 about 1/10th as well as
      dog CCK-58, indicating a marked effect on C-terminal immunoreactivity. Cat CCK-58
      with a serine at position 40, the same residue found in pig, mouse, cow and
      rabbit CCK-58, can be used as a unique bioprobe for defining how amino terminal
      amino acids influence the structure and bioactivity of the carboxyl terminal
      region of CCK.

PMID- 16904072
TI  - Early responses of osteoblast-like cells to different mechanical signals through
      various signaling pathways.
AB  - This study was to examine the effects of mechanical stimuli alone and coupled
      with some inhibitors of related signaling pathways on early cellular responses.
      MG-63 cells were subjected to cyclic uniaxial compressive or tensile strain at
      4000 microstrain, produced by four-point bending system. The effects of
      mechanical strains alone and coupled with inhibitors of microfilament and
      receptor tyrosine kinase (RTK) on activation of extracellular signal-regulated
      kinase (ERK), c-fos mRNA, and c-Fos protein were examined. ERK could be activated
      by mechanical stimuli in 5 min and so could be c-fos mRNA and c-Fos protein in 30
      min. Tensile stress had a more obvious effect than compressive one. Early
      cellular responses were connected with cytoskeleton and RTK pathways during the
      transduction of mechanical signals. The property of strains was an influential
      factor for the activation effects.

PMID- 16904073
TI  - Characterization of Ca2+ influx induced by dimethylphytosphingosine and
      lysophosphatidylcholine in U937 monocytes.
AB  - Calcium is a ubiquitous second messenger controlling a broad range of cellular
      functions. We previously observed that N,N-dimethyl-D-ribo-phytosphingosine
      (DMPH) and lysophosphatidylcholine (LPC) induced Ca2+ influx across the plasma
      membrane in U937 monocytes. In this study, we characterized the Ca2+ influx
      induced by DMPH and LPC. L-type voltage-gated Ca2+ channel blockers, verapamil
      and nifedipine, significantly reduced LPC-induced Ca2+ influx, but not DMPH
      induced one. On the other hand, non-specific Ca2+ channel blockers, Ga3+ and
      La3+, considerably reduced DMPH- and LPC-induced Ca2+ influx. Preincubation of
      the cells with forskolin enhanced DMPH-induced Ca2+ influx, however, LPC-induced
      Ca2+ influx was not affected by the treatment. The enhancement by forskolin was
      blocked by KT5720, a PKA inhibitor. We also confirmed the presence of TRPM7 and
      absence of TRPM3 in U937 cells. Therefore, our characterization of Ca2+ influx in
      U937 human monocytes shows the presence of two different types of Ca2+ channels
      modulated by lysolipid molecules, DMPH and LPC. LPC may induce Ca2+ influx via L
      type Ca2+ channels and DMPH seems to induce Ca2+ influx through TRPM7 in U937
      human monocytes.

PMID- 16904074
TI  - Oxidized LDL binding to LOX-1 upregulates VEGF expression in cultured bovine
      chondrocytes through activation of PPAR-gamma.
AB  - It has been reported that vascular endothelial growth factor (VEGF) and its
      receptors play an important role in the destruction of articular cartilage in
      osteoarthritis through increased production of matrix metalloproteinases. We
      investigated whether the oxidized low-density lipoprotein (ox-LDL) binding to
      lectin-like ox-LDL receptor-1 (LOX-1) upregulates VEGF expression in cultured
      bovine articular chondrocytes (BACs). Ox-LDL markedly increased VEGF mRNA
      expression and protein release in time- and dose-dependent manners, which was
      significantly suppressed by anti-LOX-1 antibody pretreatment. Activation of
      peroxisome proliferator-activated receptor (PPAR)-gamma was evident in BACs with
      ox-LDL addition and was attenuated by anti-LOX-1 antibody. The specific PPAR
      gamma inhibitor GW9662 suppressed ox-LDL-induced VEGF expression. These results
      suggest that the ox-LDL/LOX-1 system upregulates VEGF expression in articular
      cartilage, at least in part, through activation of PPAR-gamma and supports the
      hypothesis that ox-LDL is involved in cartilage degradation via LOX-1.

PMID- 16904075
TI  - Gcn5p contributes to the bidirectional character of the UGA3-GLT1 yeast promoter.
AB  - Analysis of the UGA3-GLT1 bidirectional promoter has indicated that its
      transcriptional activation is determined by the combined action of Gcn4p and
      Gln3p, and that its bidirectional character is influenced by chromatin
      organization, through the action of an Abf1p binding site and a polydAdTtract.
      Results presented in this paper show that lack of Gcn5p impairs histone
      acetylation and nucleosomal organization of the UGA3-GLT1 promoter, resulting in
      an asymmetrical transcriptional activation response of UGA3 and GLT1. The
      phenotype displayed by a double mutant impaired in GCN5 and in the Abf1p binding
      site indicates that the combined action of these two elements determines the
      bidirectional capacity of the UGA3-GLT1 intergenic region.

PMID- 16904076
TI  - A novel function of Nur77: physical and functional association with protein
      kinase C.
AB  - Despite the involvement in diverse physiological process and pleiotropic
      expression profile, the molecular functions of Nur77 are not likely to be fully
      elucidated. From the effort to find a novel function of Nur77, we detected
      molecular interaction between Nur77 and PKC. Details of interaction revealed that
      C-terminal ligand binding domain (LBD) of Nur77 specifically interacted with
      highly conserved glycine-rich loop of PKC required for catalytic activity. This
      molecular interaction resulted in inhibition of catalytic activity of PKCtheta by
      Nur77. C-terminal LBD of Nur77 is sufficient for inhibiting the phosphorylation
      of substrate by PKCtheta. Ultimately, inhibition of catalytic activity by Nur77
      is deeply associated with repression of PKC-mediated activation of AP-1 and NF
      kappaB. Therefore, these findings demonstrate a novel function of Nur77 as a PKC
      inhibitor and give insights into molecular mechanisms of various Nur77-mediated
      physiological phenomena.

PMID- 16904077
TI  - Allele-specific MMP-3 transcription under in vivo conditions.
AB  - A common matrix metalloproteinases-3 (MMP-3) -1612 5A/6A promoter polymorphism is
      associated with risk for cardiovascular disease, rheumatoid arthritis, and other
      diseases. Here we used the haplotype chromatin immunoprecipitation method to
      study allele-specific MMP-3 expression under in vivo conditions in heterozygous
      THP-1 cells. Pyrosequencing was used to analyse the ratio of 5A-allele to 6A
      allele after chromatin immunoprecipitation using an antibody against
      phosphorylated active RNA polymerase II. There was no allele-specific difference
      in transcriptional activity during basal conditions, i.e., in unstimulated
      monocytic THP-1 cells. However, after stimulation of MMP-3 expression by monocyte
      differentiation or incubation with IL-1beta, the haplotype containing the 5A
      allele was associated with higher transcriptional activity compared with the 6A
      containing haplotype. Electromobility shift assay demonstrated increased binding
      of nuclear proteins to the 5A-allele after monocyte differentiation. In
      conclusion, the common MMP-3 5A/6A promoter polymorphism appears to be functional
      only during specific environmental conditions involving inflammation.

PMID- 16904078
TI  - Processing new and repeated names: effects of coreference on repetition priming
      with speech and fast RSVP.
AB  - Previous research has shown that the process of establishing coreference with a
      repeated name can affect basic repetition priming. Specifically, repetition
      priming on some measures can be eliminated for repeated names that corefer with
      an entity that is prominent in the discourse model. However, the exact nature and
      timing of this modulating effect of discourse are not yet understood. Here, we
      present two ERP studies that further probe the nature of repeated name
      coreference by using naturally produced connected speech and fast-rate RSVP
      methods of presentation. With speech we found that repetition priming was
      eliminated for repeated names that coreferred with a prominent antecedent. In
      contrast, with fast-rate RSVP, we found a main effect of repetition that did not
      interact with sentence context. This indicates that the creation of a discourse
      model during comprehension can affect repetition priming, but the nature of this
      effect may depend on input speed.

PMID- 16904079
TI  - Molecular basis underlying the poly C binding protein 1 as a regulator of the
      proximal promoter of mouse mu-opioid receptor gene.
AB  - Previous studies showed poly C binding protein 1 (PCBP) participating in the mu
      opioid receptor (MOR) gene regulation via binding to a single-stranded (ss) DNA
      element. In this report, we therefore investigate the molecular basis of PCBP
      regulating the MOR gene expression. Various truncated PCBPs, including one domain
      (KH1, KH2, variable or KH3), two- (K12, K2v or Kv3) or three-sequential domains
      (K12v or K2v3), were constructed. The MOR ssDNA binding abilities of these
      truncated PCBPs were examined using electrophoretic mobility shift assay (EMSA).
      KH1 domain possessed a strong MOR ssDNA binding activity. Variable domain
      displayed no binding, and KH2 or KH3 domain possessed a weak MOR ssDNA binding
      activity. Binding of two-domain PCBPs indicated an additive effect of two-domain
      combinations. Interestingly, K2v3, a three-domain PCBP, displayed as strong ssDNA
      binding as that of K12v, suggesting synergism of KH2, KH3 and variable domains
      for the binding activity. Functional analysis demonstrated one-domain PCBPs
      exhibiting no transactivation on the MOR proximal promoter. Two-domain PCBPs
      displayed approximately 20% activity, while three-domain PCBPs displayed 70%-85%
      of full-length PCBP activity. Taken together, these results suggested that no
      single domain possessed sufficient functional activity to serve as an independent
      transactivation domain, and the combination of three sequential domains was
      necessary for its optimal activity to activate the MOR proximal promoter. In
      summary, our data suggested that cooperativity of three sequential domains is
      essential for PCBP functioning as a MOR gene regulator. Various ways in which
      this cooperativity could occur are discussed.

PMID- 16904080
TI  - Unexpected expression of orexin-B in basal conditions and increased levels in the
      adult rat hippocampus during pilocarpine-induced epileptogenesis.
AB  - Orexin-A (OX-A) and -B (OX-B) peptides present in the hippocampus are considered
      to be exclusively contained in fibers arising from hypothalamus neurons, which
      were established as the only source of orexins (OXs). Because OX-A is known to
      exert excitatory actions in the hippocampus, we hypothesized that the level of
      OXs targeted toward the hippocampus may be increased following status-epilepticus
      (SE)-induced epileptogenesis in the rat pilocarpine model of temporal lobe
      epilepsy. We found that tissue concentration of prepro-OX mRNA, which encodes for
      both peptides, rapidly decreased in the hypothalamus of rats having experienced
      pilocarpine-induced SE (Pilo-SE) followed by a reduced density of OX-A and OX-B
      immunopositive fibers arising from these neurons. By contrast, it was unexpected
      to detect within the hippocampus the presence of prepro-OX mRNA in basal
      conditions and to evidence its up-regulation during the 1- to 3-day period
      following Pilo-SE. The number of prepro-OX mRNA copies determined by real-time RT
      PCR was approximately 50-fold lower in the hippocampus than that in the
      hypothalamus, precluding the use of in situ hybridization to localize the cells
      which synthesize the transcript within the hippocampus. The increase in prepro-OX
      mRNA level within the hippocampus was accompanied by the detection of OX-B-like
      immunoreactivity 2-3 days post-SE, not only in pyramidal neurons, granule cells
      and cell bodies resembling interneurons, but also in some astrocytes scattered
      throughout the hippocampus. The present data suggest that the gene encoding OXs
      can be activated in the hippocampus, which may play a role in the pathogenesis of
      epilepsy.

PMID- 16904081
TI  - MicroRNA gene expression in the mouse inner ear.
AB  - MicroRNAs (miRNAs) are small non-coding RNAs that function through the RNA
      interference (RNAi) pathway and post-transcriptionally regulate gene expression
      in eukaryotic organisms. While miRNAs are known to affect cellular proliferation,
      differentiation, and morphological development, neither their expression nor
      roles in mammalian inner ear development have been characterized. We have
      investigated the extent of miRNA expression at various time points throughout
      maturation of the postnatal mouse inner ear by microarray analysis. Approximately
      one third of known miRNAs are detected in the inner ear, and their expression
      persists to adulthood. Expression of such miRNAs is validated by quantitative PCR
      and northern blot analysis. Further analysis by in situ hybridization
      demonstrates that certain miRNAs exhibit cell-specific expression patterns in the
      mouse inner ear. Notably, we demonstrate that miRNAs previously associated with
      mechanosensory cells in zebrafish are also expressed in hair cells of the
      auditory and vestibular endorgans. Our results demonstrate that miRNA expression
      is abundant in the mammalian inner ear and that certain miRNAs are evolutionarily
      associated with mechanosensory cell development and/or function. The data suggest
      that miRNAs contribute substantially to genetic programs intrinsic to development
      and function of the mammalian inner ear and that specific miRNAs might influence
      formation of sensory epithelia from the primitive otic neuroepithelium.

PMID- 16904083
TI  - When sex meets syntactic gender on a neural basis during pronoun processing.
AB  - We used event-related functional magnetic resonance imaging (erfMRI) to
      investigate the neural basis of biological and syntactic gender integration
      during pronoun processing in German sentences about persons or things. German
      allows for separating both processes experimentally. Overall, syntactic
      processing activated areas adjacent to Broca's area (BA 44), whereas processing
      of the biological sex, in addition, involved the supramarginal gyrus (BA 39). A
      previously reported event-related potential study using identical material
      suggests that syntactic and semantic information is integrated 400-700 ms after
      target onset, visible in both cases as a P600 but with different effect sizes.
      The fMRI and ERP results illuminate that pronoun processing involves a highly
      dynamic spatiotemporal integration of syntactic and biological information
      depending on the type of the antecedent and whether or not a violation is
      involved. The results are discussed in the context of cognitive models of pronoun
      processing.

PMID- 16904082
TI  - The effect of Zn(II) and streptozotocin administration in the mouse brain.
AB  - Streptozotocin is a natural antibiotic produced by Streptomyces achromogenes able
      to induce diabetes in experimental animals. Among various toxic properties,
      streptozotocin is a potent source for reactive oxygen species. In this paper, we
      report the biological response of brain, upon treatment with streptozotocin in
      terms of metal ions dismetabolism and metallothionein expression. In addition,
      important information on the preventive effect of zinc in eliciting the
      pharmacological effect of the drug are reported, in relation to the effective
      role of the metal ions in inducing metallothionein synthesis. In the brain,
      streptozotocin treatment affects mostly the hippocampus and cerebellum as shown
      by a high GAFP and MT-I-II immunopositivity of glial cells. The Zn pre-treatment
      reduces significantly, as a general effect, the occurrence of hyperglycaemic
      status. At the brain level, the observed astrocytosis is strongly reduced. The
      high inducibility of MT represents a rapid and convenient response able to
      prevent the deleterious effects consequent to the oxidative stress. All together
      these results support the efficacy of the Zn treatment in order to prevent
      streptozotocin effects, including brain tissues.

PMID- 16904084
TI  - A decrease of cell proliferation by hypothermia in the hippocampus of the
      neonatal rat.
AB  - Hypothermia is a potential therapy for cerebral hypoxic ischemic injury of not
      only adults but also neonates. However, the side effects of hypothermia in the
      developing brain, where a massive amount of neurogenesis occurs, remain unclear.
      We investigated the proliferation of neural progenitor cells by systemic
      application of the thymidine analog 5-bromodeoxyuridine (BrdU) in neonatal rats
      in a severe hypothermic environment. The rat pups were divided into two groups, a
      hypothermia group (30 degrees C: n=10) and a normothermia group (37 degrees C:
      n=10). After the pups were placed for 21 h in each environment, 100 mg/kg/day of
      BrdU was injected intraperitoneally to label dividing cells, and then the pups
      were sacrificed at 24 h. We examined the number of BrdU-labeled cells in the
      subventricular zone of the periventricle and the subgranular zone of the dentate
      gyrus. In the hypothermic environment, BrdU-labeled cells significantly decreased
      in number in the dentate gyrus, but not in the periventricular region. Thus, the
      severe hypothermic environment induced a decrease of neurogenesis in the neonatal
      rat. These observations are noteworthy regarding clinical hypothermia therapy
      following cerebral hypoxic ischemic injury during the perinatal period.

PMID- 16904085
TI  - Developmental timeframes for induction of microgyria and rapid auditory
      processing deficits in the rat.
AB  - Induction of a focal freeze lesion to the skullcap of a 1-day-old rat pup leads
      to the formation of microgyria similar to those identified postmortem in human
      dyslexics. Rats with microgyria exhibit rapid auditory processing deficits
      similar to those seen in language-impaired (LI) children, and infants at risk for
      LI and these effects are particularly marked in juvenile as compared to adult
      subjects. In the current study, a startle response paradigm was used to
      investigate gap detection in juvenile and adult rats that received bilateral
      freezing lesions or sham surgery on postnatal day (P) 1, 3 or 5. Microgyria were
      confirmed in P1 and 3 lesion rats, but not in the P5 lesion group. We found a
      significant reduction in brain weight and neocortical volume in P1 and 3 lesioned
      brains relative to shams. Juvenile (P27-39) behavioral data indicated significant
      rapid auditory processing deficits in all three lesion groups as compared to sham
      subjects, while adult (P60+) data revealed a persistent disparity only between P1
      lesioned rats and shams. Combined results suggest that generalized pathology
      affecting neocortical development is responsible for the presence of rapid
      auditory processing deficits, rather than factors specific to the formation of
      microgyria per se. Finally, results show that the window for the induction of
      rapid auditory processing deficits through disruption of neurodevelopment appears
      to extend beyond the endpoint for cortical neuronal migration, although, the
      persistent deficits exhibited by P1 lesion subjects suggest a secondary
      neurodevelopmental window at the time of cortical neuromigration representing a
      peak period of vulnerability.

PMID- 16904086
TI  - Protein expression and mRNA cellular distribution of the NKCC1 cotransporter in
      the dorsal root and trigeminal ganglia of the rat.
AB  - Primary afferent neurons maintain depolarizing responses to GABA into adulthood.
      The molecular basis for this GABAergic response appears to be the Na+K+2Cl-
      cotransporter NKCC1 that contributes to the maintenance of a high intracellular
      chloride concentration. Recently, a role for NKCC1 has been proposed in
      nociceptive processing which makes it timely to gain a better understanding of
      the distribution of NKCC1 in sensory ganglia. Here, we describe that, in the rat,
      NKCC1 mRNA is predominately expressed by small and medium diameter dorsal root
      (DRG) and trigeminal (TG) ganglion neurons. The colocalization of NKCC1 mRNA with
      sensory neuron population markers was assessed. In the DRG, many NKCC1 mRNA
      expressing neurons colocalized peripherin (57.0+/-2.5%), calcitonin-gene-related
      peptide (CGRP, 39.2+/-4.4%) or TRPV1 immunoreactivity (50.0+/-1.9%) whereas only
      8.7+/-1.2% were co-labeled with a marker for large diameter afferents (N52).
      Similarly, in the TG, NKCC1 mRNA-expressing neurons frequently colocalized
      peripherin (50.0+/-3.0%), CGRP (35.4+/-2.6%) or TRPV1 immunoreactivity (44.7+/
      1.2%) while 14.8+/-1.3% were co-labeled with the N52 antibody. NKCC1 mRNA was
      also detected in satellite glial (SGCs) in both the DRG and TG. Colocalization of
      NKCC1 protein with the SGC marker NG2 confirmed the phenotype of these NKCC1
      expressing glial cells. In contrast to in situ hybridization experiments, we did
      not observe NKCC1 immunoreactivity in primary afferent somata. These findings
      suggest that NKCC1 is expressed in anatomically appropriate cells in order to
      modulate GABAergic responses in nociceptive neurons. Moreover, these results
      suggest the possibility of a functional role of NKCC1 in the glial cells closely
      apposed to primary sensory afferents.

PMID- 16904087
TI  - Glutamate receptor-mediated inhibition of L-glutamate efflux from cerebral cortex
      in vitro.
AB  - We tested whether glutamate receptor ligands affect oxygen-glucose deprivation
      evoked L-glutamate efflux from adult rat cerebrocortical prisms. The
      uncompetitive NMDA antagonist AR-R15896AR inhibited efflux (IC50 34 microM, 87%
      maximal inhibition). AMPA/kainate receptor blockade (NBQX, 100 microM) or Group
      II metabotropic glutamate receptor activation (DCG-IV, 10 microM) inhibited
      efflux (41%, 67% respectively) but Group I mGluR blockade (CPCCOEt/MPEP, 10
      microM) was without effect. These data support a modulatory effect of glutamate
      receptors on L-glutamate efflux.

PMID- 16904088
TI  - Erythropoietin protects cardiomyocytes from apoptosis via up-regulation of
      endothelial nitric oxide synthase.
AB  - OBJECTIVE: Erythropoietin (EPO), a cytokine best known for its ability to
      increase red blood cell mass, has recently been shown to protect cardiomyocytes
      from apoptotic cell death. The objective of the present study was to investigate
      the role of endothelial nitric oxide synthase (eNOS) in the anti-apoptotic
      effects of EPO in cardiomyocytes. METHODS AND RESULTS: Neonatal mouse ventricular
      cardiomyocytes were isolated and cultured from wild-type and eNOS(-/-) mice.
      Treatment with EPO significantly reduced apoptosis induced by norepinephrine (NE)
      in the wild-type cardiomyocytes. The reduction of apoptosis was associated with
      significant increases in eNOS expression, phosphorylation and NO production.
      However, the anti-apoptotic effects of EPO were significantly decreased in wild
      type cardiomyocytes treated with L-NAME, which inhibits nitric oxide synthase
      activity. The results were further confirmed using eNOS(-/-) cardiomyocytes. To
      investigate the in vivo significance of eNOS in mediating the anti-apoptotic
      effects of EPO, wild-type and eNOS(-/-) mice were subjected to myocardial
      ischemia and reperfusion. EPO decreased myocardial apoptosis and infarct size in
      wild-type mice. However, the protective effects of EPO were significantly
      diminished in eNOS(-/-) mice. CONCLUSIONS: EPO increases eNOS expression and NO
      production in cardiomyocytes. The anti-apoptotic effects of EPO in cardiomyocytes
      are mediated by eNOS-derived NO production.

PMID- 16904089
TI  - High altitude-induced pulmonary oedema.
AB  - Almost one mountain trekker or climber out of two develops several symptoms of
      high altitude illness after a rapid ascent (> 300 m/day) to an altitude above
      4000 m. Individual susceptibility is the most important determinant for the
      occurrence of high altitude pulmonary oedema (HAPE). Symptoms associated with
      HAPE are incapacitating fatigue, chest tightness, dyspnoea at the slightest
      effort, orthopnoea, and cough with due to haemoptysis in an advanced stage of the
      disease pink frothy sputum. The hallmark of HAPE is an excessively elevated
      pulmonary artery pressure (mean pressures of 35 and 55 mm Hg), which precedes the
      development of pulmonary oedema. Elevated pulmonary capillary pressure and
      protein- as well as red blood cell-rich oedema fluid without signs of
      inflammation in its early stage are characteristic findings. Furthermore,
      decreased fluid clearance from the alveoli may contribute to this non-cardiogenic
      pulmonary oedema. Immediate descent or supplemental oxygen and nifedipine are
      recommended until descent is possible. Susceptible individuals can prevent HAPE
      by slow ascent: an average gain of altitude not exceeding 400 m/day above an
      altitude of 2500 m. If progressive high altitude acclimatization is not possible,
      a prophylaxis with nifedipine should be recommended.

PMID- 16904090
TI  - Runx-dependent regulation of G-protein gamma3 expression in T-cells.
AB  - Heterotrimeric G-proteins control diverse biological processes by conveying
      signals from seven-transmembrane receptors to intracellular effectors. Although
      their signaling roles were originally ascribed to their GTP-bound alpha-subunits,
      more recent evidence points to the equally active roles played by their betagamma
      dimers. To elucidate the individual contributions of their gamma-subtypes, we
      used a gene targeting approach to show that mice lacking the gamma3-subtype
      display a defective T-cell dependent immune response. To identify the cellular
      basis for this defect, we demonstrated that gamma3-mRNA is strongly induced in
      activated CD4+ T-cells. To determine the mechanism for this regulated expression,
      we used several strategies to identify the importance of a Runx consensus
      sequence element in the first intron of the gamma3 gene and the Runx1 protein.
      Overall, these data provide the first genetic evidence for the tight regulation
      and involvement of the G protein gamma3-subtype in mounting an effective immune
      response in mice.

PMID- 16904091
TI  - Differential expression of glutathione-S-transferase isoenzymes in various types
      of anemia in Taiwan.
AB  - BACKGROUND: Published reports concerning the expression of GST in various anemias
      including aplastic, hemolytic, iron deficiency and thalassemia anemia has been
      insufficient. We improved the conventional GST assay by incorporating a
      chloroform treatment to remove the interference of hemoglobin and evaluated the
      altered expression of GSTs in various anemias in Taiwan. METHODS: We incorporated
      a chloroform treatment to eliminate the interference of hemoglobin. Erythrocyte
      total GST and isoenzymes activities from 35 control subjects and 125 subjects of
      various anemias, including aplastic, hemolytic, iron deficiency and thalassemia
      anemias were measured spectrophotometrically. RESULTS: Chloroform treatment did
      not significantly affect GST activities in erythrocytes of control subjects while
      the activities of erythrocyte total GST and alpha-GST were significantly
      increased in all anemic patients (P<0.001). The expression of mu-GST was
      significantly decreased, although at a less extent, in cases of aplastic, iron
      deficiency and thalassemia anemia (P<0.05), but pi-GST was not physiologically
      different in various types of anemia. CONCLUSION: The determination of changes in
      erythrocyte GST activity is a promising indicator of oxidative stress conditions
      that occur in various types of anemia. Measurement of GST activity might be
      useful for the evaluation of prophylactic treatment in trials of antioxidant
      strategies.

PMID- 16904092
TI  - Oxidative injury and antioxidants in coronary artery bypass graft surgery: off
      pump CABG significantly reduces oxidative stress.
AB  - BACKGROUND: Coronary artery bypass grafting (CABG) can now be performed with or
      without cardiopulmonary bypass. The former entails global ischemia followed by
      reperfusion after declamping, whereas the latter does not. In view of growing
      evidence that reperfusion is associated with oxidative stress, we studied the
      extent of oxidative stress and antioxidant status in patients undergoing on-pump
      and off-pump CABG to determine whether the latter significantly reduces oxidative
      stress. METHODS: Thirty patients were initially enrolled for the study. The
      inclusion criteria included patients with atherosclerotic triple vessel disease,
      undergoing elective CABG, with good LV function, no major risk factors for
      surgery, with all biochemical investigations within normal limits, having stable
      angina and no history of previous infarct. Patients with valvular heart disease,
      ventricular aneurysm, heart failure and poor left ventricular function were
      excluded. These were alternately posted for on-pump and off-pump CABG. Eight
      patients were excluded as they developed unforeseen complications during the
      surgery. Out of the remaining 22 patients, 13 underwent off-pump CABG and 9
      underwent on-pump CABG. Five blood samples were collected; baseline, 5, 15, 60
      min and 24 h after reperfusion. Samples were analyzed for thiobarbituric acid
      reactive substances (TBARS), glutathione (G-SH) and catalase (CAT). The results
      were compared with their preanaesthetic levels in both the groups and also with
      20 age- and sex-matched normal healthy individuals. RESULTS: Lipid peroxidation
      was significantly increased after reperfusion in patients undergoing on-pump
      CABG, maximum increase (p<0.0001) was seen 1 h after reperfusion, whereas off
      pump CABG reduces oxidative stress. The G-SH levels were significantly decreased
      after reperfusion in on-pump and off-pump CABG patients, maximum decrease
      (p<0.0001) was seen 5 min after reperfusion in on-pump CABG. The catalase
      activity was significantly increased after reperfusion in on-pump and off-pump
      CABG patients, maximum increase (p<0.0001) was seen 1 h after reperfusion in on
      pump CABG. CONCLUSION: Significant increase in oxidative stress was seen in
      patients undergoing on-pump CABG, whereas oxidative stress was less in off-pump
      CABG patients. The G-SH levels were decreased and Catalase activity was increased
      significantly in both on-pump and off-pump CABG patients.

PMID- 16904094
TI  - The emergence of psychopathy: implications for the neuropsychological approach to
      developmental disorders.
AB  - In this paper, I am going to examine the disorder of psychopathy and consider how
      genetic anomalies could give rise to the relatively specific neuro-cognitive
      impairments seen in individuals with this disorder. I will argue that genetic
      anomalies in psychopathy reduce the salience of punishment information (perhaps
      as a function of noradrenergic disturbance). I will argue that the ability of the
      amygdala to form the stimulus-punishment associations necessary for successful
      socialization is disrupted and that because of this, individuals with psychopathy
      do not learn to avoid actions that will harm others. It is noted that this model
      follows the neuropsychological approach to the study of developmental disorders,
      an approach that has been recently criticized. I will argue that these criticisms
      are less applicable to psychopathy. Indeed, animal work on the development of the
      neural systems necessary for emotion, does not support a constructivist approach
      with respect to affect. Importantly, such work indicates that while environmental
      effects can alter the responsiveness of the basic neural architecture mediating
      emotion, environmental effects do not construct this architecture. However,
      caveats to the neuropsychological approach with reference to this disorder are
      noted.

PMID- 16904093
TI  - Cardiac titin: structure, functions and role in disease.
AB  - Titin is a giant sarcomeric protein found in both cardiac and skeletal muscle. In
      the heart, the structure, functions and role of titin in disease have begun to be
      elucidated over the last decade. Titin's N-terminus is anchored in the Z-disk
      while C-terminal domains are bound to the thick filament. The I-band segment is a
      complex molecular spring consisting of PEVK and tandem Ig segments as well as
      variable N2B and N2A elements. The latter determine titin's two isoforms. N2B
      alone is present in the smaller and stiffer N2B isoform and both N2A and N2B
      elements are present in the larger, more compliant N2BA isoform. Large mammals co
      express both isoforms, while normal rodents have virtually exclusively N2B titin.
      With sarcomere stretch, titin's I-band segment elongates and develops passive
      tension. Titin is the predominant determinant of cardiomyocyte passive tension
      over the physiologic sarcomere length range. With contraction below slack length,
      the thick filament drags titin in the opposite direction such that extension of
      the spring results in generation of a restoring force resulting in elastic
      recoil. In addition to its mechanical properties, a role is emerging for titin as
      a major biomechanical sensing and signaling molecule. Moreover, recent studies
      indicate that titin undergoes dynamic isoform and possibly phosphorylation
      changes in disease.

PMID- 16904095
TI  - The influence of intention on masked priming: a study with semantic
      classification of words.
AB  - Unconscious perception is commonly described as a phenomenon that is not under
      intentional control and relies on automatic processes. We challenge this view by
      arguing that some automatic processes may indeed be under intentional control,
      which is implemented in task-sets that define how the task is to be performed. In
      consequence, those prime attributes that are relevant to the task will be most
      effective. To investigate this hypothesis, we used a paradigm which has been
      shown to yield reliable short-lived priming in tasks based on semantic
      classification of words. This type of study uses fast, well practised
      classification responses, whereby responses to targets are much less accurate if
      prime and target belong to a different category than if they belong to the same
      category. In three experiments, we investigated whether the intention to classify
      the same words with respect to different semantic categories had a differential
      effect on priming. The results suggest that this was indeed the case: Priming
      varied with the task in all experiments. However, although participants reported
      not seeing the primes, they were able to classify the primes better than chance
      using the classification task they had used before with the targets. When a
      lexical task was used for discrimination in experiment 4, masked primes could
      however not be discriminated. Also, priming was as pronounced when the primes
      were visible as when they were invisible. The pattern of results suggests that
      participants had intentional control on prime processing, even if they reported
      not seeing the primes.

PMID- 16904096
TI  - A new hybrid method based on fuzzy-artificial immune system and k-nn algorithm
      for breast cancer diagnosis.
AB  - The use of machine learning tools in medical diagnosis is increasing gradually.
      This is mainly because the effectiveness of classification and recognition
      systems has improved in a great deal to help medical experts in diagnosing
      diseases. Such a disease is breast cancer, which is a very common type of cancer
      among woman. As the incidence of this disease has increased significantly in the
      recent years, machine learning applications to this problem have also took a
      great attention as well as medical consideration. This study aims at diagnosing
      breast cancer with a new hybrid machine learning method. By hybridizing a fuzzy
      artificial immune system with k-nearest neighbour algorithm, a method was
      obtained to solve this diagnosis problem via classifying Wisconsin Breast Cancer
      Dataset (WBCD). This data set is a very commonly used data set in the literature
      relating the use of classification systems for breast cancer diagnosis and it was
      used in this study to compare the classification performance of our proposed
      method with regard to other studies. We obtained a classification accuracy of
      99.14%, which is the highest one reached so far. The classification accuracy was
      obtained via 10-fold cross validation. This result is for WBCD but it states that
      this method can be used confidently for other breast cancer diagnosis problems,
      too.

PMID- 16904097
TI  - Assessment of the classification capability of prediction and approximation
      methods for HRV analysis.
AB  - The goal of this paper is to examine the classification capabilities of various
      prediction and approximation methods and suggest which are most likely to be
      suitable for the clinical setting. Various prediction and approximation methods
      are applied in order to detect and extract those which provide the better
      differentiation between control and patient data, as well as members of different
      age groups. The prediction methods are local linear prediction, local exponential
      prediction, the delay times method, autoregressive prediction and neural
      networks. Approximation is computed with local linear approximation, least
      squares approximation, neural networks and the wavelet transform. These methods
      are chosen since each has a different physical basis and thus extracts and uses
      time series information in a different way.

PMID- 16904098
TI  - Cryovial with partial membrane sealing can prevent liquid nitrogen penetration in
      submerged storage.
AB  - Cryopreservation is one of the fundamental techniques in life science. To
      preserve the viability of cells and tissues, many researchers use plastic
      cryogenic vials and immerse them into liquid nitrogen for long-term storage.
      However, the non-sterile liquid nitrogen usually infiltrates into the vials and
      may cause a high rate of microbial contamination, and even some explosive
      incidents upon retrieval. To prevent these drawbacks while retaining the benefit
      of constant ultra-low temperature in submerged liquid nitrogen, we used a heat
      sealable membrane to cover the upper portion of vials. After heat-sealing, the
      vials were completely free of liquid nitrogen penetration in the submerging test.
      Moreover, the sealing process did not affect the cell viability. This modified
      protocol provides an easy and efficient tool to ensure the integrity of
      biospecimens in long-term storage without interfering with existing cryobox
      storage systems.

PMID- 16904099
TI  - A beta1,4-galactosyltransferase is required for convergent extension movements in
      zebrafish.
AB  - Our understanding of how complex carbohydrates function during embryonic
      development is still very limited, primarily due to the large number of
      glycosyltransferases now known to be involved in their synthesis. To overcome
      these limitations, we have taken advantage of the zebrafish system to analyze the
      function of complex carbohydrates during development by down-regulating the
      expression of specific glycosyltransferases. Herein, we report the identification
      of the zebrafish ortholog of mammalian beta1,4-galactosyltransferase I,
      beta4GalT1, and its requirement for proper convergent extension movements during
      gastrulation. beta4GalT1 is expressed in the oocyte and throughout the embryo
      during the first 24 h of development. Knockdown of zebrafish beta4GalT1 by two
      independent morpholino oligonucleotides results in embryos with a truncated
      anterior-posterior axis, as well as elongated somites and moderate defects in the
      patterning of the head mesenchyme. Co-injection of zebrafish beta4GalT1 mRNA
      returns galactosyltransferase activity to control levels and rescues the defects
      produced by morpholino oligonucleotides. In situ hybridizations of various
      molecular markers reveal that the axial mesoderm of epiboly stage embryos is
      abnormally widened in beta4GalT1 morphants, indicative of abnormal convergent
      extension. Consistent with this, the rate of anterior-posterior axis elongation
      is reduced relative to control-injected embryos, similar to that seen in known
      convergent extension mutants. Among the many potential substrates for beta4GalT1
      is laminin, a principle component of the extracellular matrix that supports cell
      movements such as those that occur during convergent extension. Previous in vitro
      studies have shown that the galactosylation status of laminin directly influences
      its ability to support cell spreading and migration. In this regard, laminin
      isolated from beta4GalT1 morphant embryos is poorly galactosylated, which may
      contribute to defective cell migration during convergent extension movements.
      This work demonstrates that zebrafish can be used to identify critical
      developmental roles for specific glycosyltransferases that would not be obvious
      otherwise, such as an absolute requirement for beta4GalT1 during convergent
      extension movements.

PMID- 16904100
TI  - FNDC3A is required for adhesion between spermatids and Sertoli cells.
AB  - Symplastic spermatids (sys) male mice are sterile due to a recessive mutation
      that causes defective adhesion between spermatids and Sertoli cells within the
      seminiferous epithelium. We show that the mutation in sys mice involves a
      deletion of 1.24 Mb of chromosome 14. Comparative genomic analysis suggests that
      this region contains only one gene, Fndc3a. A genetic complementation analysis
      using mice with a specific mutation within Fndc3a verifies that mutation of
      Fndc3a is the cause of male sterility in sys mice. Fndc3a is a member of a three
      gene family in mice. Fndc3a, which is expressed in several tissues including
      testis, encodes a novel protein composed of a proline-rich amino-terminus, nine
      fibronectin type-III domains, and a hydrophobic carboxy-terminus. The proline
      rich region of each family member contains conserved amino acids that include a
      PPGY consensus binding site for type I WW domain containing proteins. The
      hydrophobic carboxy-terminus is similar to that found in 'tail-anchored'
      proteins, integral membrane proteins that are localized to the cytosolic face of
      the endoplasmic reticulum. Immunohistochemical staining indicated that FNDC3A
      localizes to the acrosome of spermatids, as well as to Leydig cells in the mouse
      testis. Acrosomal localization of FNDC3A is observed in spermatids between step 2
      and step 10 inclusive. In step 12 spermatids, FNDC3A is largely absent from the
      acrosomal region with immunostaining being localized to vesicular structures
      located within the cytoplasm of elongate spermatids. Models are presented for the
      function of FNDC3A in mediating spermatid-Sertoli adhesion during mouse
      spermatogenesis.

PMID- 16904101
TI  - The effect of lithium chloride on morphine-induced tolerance and dependence in
      isolated guinea pig ileum.
AB  - The chronic use of opioids is often accompanied by the development of tolerance
      and/or dependence upon these agents due to the adaptive changes in the response
      of the subject to the agent. On cellular level, these phases of altered
      responsiveness have been shown to be the sequelae of a combination of multiple
      independent components acting in concert. Changes in the number, affinity, or
      membrane trafficking of opioids receptors, the coupling of receptors to G
      proteins or in associated second messenger systems have been implicated in
      underlying the aforementioned phenomena. Several observations have been shown
      that lithium is able to contradict the expected response in animals pre-treated
      with morphine. These facts clearly manifest the involvement of lithium in at
      least one of the diverse pathways that lead to morphine dependence and/or
      tolerance. The aim of the present study was to investigate the effect of lithium
      on acute morphine-induced tolerance and dependence in an in vitro model of
      isolated guinea pig ileum which has been extensively used for the assessment of
      these effects of opioids. Morphine inhibited electrically stimulated twitch of
      ileum in a concentration-dependent manner (pD(2)=7.27+/-0.16). Tolerance to this
      effect was induced by the incubation of ileum with 2xIC(50) of morphine for 2 h
      that induced a degree of tolerance of 14.7. The co-incubation of ileum with
      morphine along lithium chloride (1 mM) reduced the degree of tolerance
      significantly (P<0.001) and restored the sensitivity of ileum to the morphine
      inhibitory effect. Lithium chloride can also reduce the expression of tolerance
      to morphine significantly (P<0.01). Dependence was induced by incubation with
      4xIC(50) of morphine for 2 h and was assessed based on naloxone-induced
      contractions (10(-5 )M). Lithium chloride (1 mM) can attenuate the development
      but not the expression of dependence to morphine as shown by the significant
      decrease in naloxone-induced contractions (P<0.05). These results suggest that
      lithium chloride can reduce the development and expression of acute tolerance to
      and development of dependence on morphine in the myenteric plexus of guinea pig
      ileum.

PMID- 16904102
TI  - Impairment of the vascular relaxation and differential expression of caveolin-1
      of the aorta of diabetic +db/+db mice.
AB  - In this study, we compared the endothelium-dependent and -independent relaxation
      of the isolated thoracic aorta of control (+db/+m) and diabetic (+db/+db)
      (C57BL/KsJ) mice. The gene expression (mRNA and protein) level of the muscarinic
      M(3) receptors, endothelial nitric oxide synthase (eNOS) and caveolin-1 of the
      aorta was also evaluated. Acetylcholine caused a concentration-dependent, N(G)
      nitro-L-arginine methyl-ester (20 microM)-sensitive relaxation, with
      approximately 100% relaxation at 10 microM, in +db/+m mice. In +db/+db mice, the
      acetylcholine-induced relaxation was significantly smaller (maximum relaxation:
      approximately 80%). The sodium nitroprusside-mediated relaxation was slightly
      diminished in +db/+db mice, compared to +db/+m mice. However, there was no
      significant difference in the isoprenaline- and cromakalim-induced relaxation
      observed in both species. The mRNA and protein expression levels of caveolin-1
      were significantly higher in the aorta of +db/+db mice. In contrast, there was no
      difference in the mRNA and protein expression levels of eNOS and muscarinic M(3)
      receptors between these mice. Our results demonstrate that the impairment of the
      acetylcholine-induced, endothelium-dependent aortic relaxation observed in
      +db/+db mice was probably associated with an enhanced expression of caveolin-1
      mRNA and protein.

PMID- 16904103
TI  - Emerging role of polyphenolic compounds in the treatment of neurodegenerative
      diseases: a review of their intracellular targets.
AB  - Aging is the major risk factor for neurodegenerative diseases such as Alzheimer's
      and Parkinson's diseases. A large body of evidence indicates that oxidative
      stress is involved in the pathophysiology of these diseases. Oxidative stress can
      induce neuronal damages, modulate intracellular signaling, ultimately leading to
      neuronal death by apoptosis or necrosis. Thus antioxidants have been studied for
      their effectiveness in reducing these deleterious effects and neuronal death in
      many in vitro and in vivo studies. Increasing number of studies demonstrated the
      efficacy of polyphenolic antioxidants from fruits and vegetables to reduce or to
      block neuronal death occurring in the pathophysiology of these disorders. These
      studies revealed that other mechanisms than the antioxidant activities could be
      involved in the neuroprotective effect of these phenolic compounds. We will
      review some of these mechanisms and particular emphasis will be given to
      polyphenolic compounds from green tea, the Ginkgo biloba extract EGb 761,
      blueberries extracts, wine components and curcumin.

PMID- 16904104
TI  - Reduction of angiocidin expression in human umbilical vein endothelial cells via
      siRNA silencing inhibits angiogenesis.
AB  - Angiocidin, a protein over-expressed in many different solid tumors and tumor
      capillary endothelial cells inhibits angiogenesis and tumor growth [Zhou, J., et
      al., 2004. Cloning and characterization of angiocidin, a tumor cell binding
      protein for thrombospondin-1. J Cell Biochem. 92, 125-146]. Since several splice
      variants of angiocidin have distinct biochemical functions in membrane transport
      and protein degradation, we sought to evaluate the function of endogenously
      expressed angiocidin in human umbilical vein endothelial (HUVE) cells using
      siRNA. We observed a 90% reduction of the target mRNA levels after 24 h.
      Endogenous angiocidin protein expression was reduced by 80% after three days, as
      evaluated by Western blot analysis. We also found that anti-angiocidin siRNA down
      regulated 90% of the protein expression of matrix metalloproteinase 2 (MMP-2) and
      50% of its gelatinolytic activity. Reduction of endogenous angiocidin completely
      inhibited endothelial cord formation on Matrigel. Cells expressing low levels of
      angiocidin grew more slowly, were less invasive and less adhesive than control
      cells. Consistent with the reported function of one of the angiocidin analogues
      S5a, we found that the expression of polyubiquitinated proteins was higher in
      anti-angiocidin siRNA-treated cells as compared to normal and control siRNA
      treated cells. These results suggest that endogenous angiocidin and its
      homologues promote endothelial cell invasion, adhesion, and angiogenesis through
      mechanisms involving polyubiquitin-dependent protein degradation and MMP-2
      expression.

PMID- 16904105
TI  - Specific deletion of CMF1 nuclear localization domain causes incomplete cell
      cycle withdrawal and impaired differentiation in avian skeletal myoblasts.
AB  - CMF1 is a protein expressed in embryonic striated muscle with onset of expression
      preceding that of contractile proteins. Disruption of CMF1 in myoblasts disrupts
      muscle-specific protein expression. Preliminary studies indicate both nuclear and
      cytoplasmic distribution of CMF1 protein, suggesting functional roles in both
      cellular compartments. Here we examine the nuclear function of CMF1, using a
      newly characterized antibody generated against the CMF1 nuclear localization
      domain and a CMF1 nuclear localization domain-deleted stable myocyte line. The
      antibody demonstrates nuclear distribution of the CMF1 protein both in vivo and
      in cell lines, with clustering of CMF1 protein around chromatin during mitosis.
      In more differentiated myocytes, the protein shifts to the cytoplasm. The CMF1
      NLS-deleted cell lines have markedly impaired capacity to differentiate.
      Specifically, these cells express less contractile protein than wild-type or full
      length CMF1 stably transfected cells, and do not fuse properly into multinucleate
      syncytia with linear nuclear alignment. In response to low serum medium, a signal
      to differentiate, CMF1 NLS-deleted cells enter G0, but continue to express
      proliferation markers and will reenter the cell cycle when stimulated by
      restoring growth medium. These data suggest that CMF1 is involved in regulation
      the transition from proliferation to differentiation in embryonic muscle.

PMID- 16904106
TI  - Microtubule disruption, not calpain-dependent loss of MAP2, contributes to
      enduring NMDA-induced dendritic dysfunction in acute hippocampal slices.
AB  - Brief exposure to excitotoxic agonists can result in substantial loss of the
      microtubule-associated protein MAP2 from neuronal dendrites, and accumulation in
      somata. A possible mechanism underling MAP2 loss is the activation of the calcium
      dependent protease calpain by excessive dendritic Ca2+-loading. The present study
      examined mechanisms of MAP2 redistribution and loss of synaptic efficacy in the
      CA1 region of acutely prepared hippocampal slices. Brief NMDA exposure resulted
      in persistent and profound inhibition of postsynaptic potentials, and loss of
      MAP2 from dendritic compartments. When Ca2+ was removed during NMDA exposure,
      synaptic potentials recovered significantly during NMDA washout, and MAP2 loss
      was reduced. Calpain inhibition with MDL 28,170 (20 microM) did not prevent the
      loss of synaptic potentials, nor did it attenuate the initial aggregation of MAP2
      into irregular dendritic swellings. However MDL 28,170 did reduce subsequent MAP2
      loss from abnormal dendritic aggregates. Pre-exposure of slices to taxol (100 nM)
      effectively prevented microtubule depolymerization following NMDA exposure, as
      well as MAP2 disorganization and loss from apical dendrites. Slices treated with
      taxol also exhibited substantial recovery of synaptic potentials after transient
      NMDA stimulus. These results demonstrate a close correspondence between the
      maintained localization of MAP2 in apical dendrites and the recovery of
      postsynaptic potentials following transient NMDA exposure. In addition, it
      appears that rather than underlying the initial disruption of microtubule
      structure via MAP2 proteolysis, calpain activity instead may contribute to the
      degradation of irregularly aggregated MAP2 observed following microtubule
      depolymerization.

PMID- 16904107
TI  - Transplantation of primed human fetal neural stem cells improves cognitive
      function in rats after traumatic brain injury.
AB  - Traumatic brain injury (TBI) often produces cognitive impairments by primary or
      secondary neuronal loss. Stem cells are a potential tool to treat TBI. However,
      most previous studies using rodent stem or progenitor cells failed to correlate
      cell grafting and cognitive improvement. Furthermore, the efficacy of fetal human
      neural stem cells (hNSCs) for ameliorating TBI cognitive dysfunction is
      undetermined. This study therefore characterized phenotypic differentiation,
      neurotrophic factor expression and release and functional outcome of grafting
      hNSCs into TBI rat brains. Adult Sprague-Dawley rats underwent a moderate
      parasagittal fluid percussion TBI followed by ipsilateral hippocampal
      transplantation of hNSCs or vehicle 1 day post-injury. Prior to grafting, hNSCs
      were treated in vitro for 7 days with our previously developed priming procedure.
      Significant spatial learning and memory improvements were detected by the Morris
      water maze (MWM) test in rats 10 days after receiving hNSC grafts. Morphological
      analyses revealed that hNSCs survived and differentiated mainly into neurons in
      the injured hippocampus at 2 weeks after grafting. Furthermore, hNSCs expressed
      and released glial-cell-line-derived neurotrophic factor (GDNF) in vitro and when
      grafted in vivo, as detected by RT-PCR, immunostaining, microdialysis and ELISA.
      This is the first direct demonstration of the release of a neurotrophic factor in
      conjunction with stem cell grafting. In conclusion, human fetal neural stem cell
      grafts improved cognitive function of rats with acute TBI. Grafted cells survived
      and differentiated into neurons and expressed and released GNDF in vivo, which
      may help protect host cells from secondary damage and aid host regeneration.

PMID- 16904109
TI  - Identification of the HIV-1 gp41 core-binding motif--HXXNPF.
AB  - The HIV-1 gp41 core, a six-helix bundle formed between the N- and C-terminal
      heptad repeats, plays a critical role in fusion between the viral and target cell
      membranes. Using N36(L8)C34 as a model of the gp41 core to screen phage display
      peptide libraries, we identified a common motif, HXXNPF (X is any of the 20
      natural amino acid residues). A selected positive phage clone L7.8 specifically
      bound to N36(L8)C34 and this binding could be blocked by a gp41 core-specific
      monoclonal antibody (NC-1). JCH-4, a peptide containing HXXNPF motif, effectively
      inhibited HIV-1 envelope glycoprotein-mediated syncytium-formation. The epitope
      of JCH-4 was proven to be linear and might locate in the NHR regions of the gp41
      core. These data suggest that HXXNPF motif may be a gp41 core-binding sequence
      and HXXNPF motif-containing molecules can be used as probes for studying the role
      of the HIV-1 gp41 core in membrane fusion process.

PMID- 16904108
TI  - 2-methoxyestradiol reduces cerebral vasospasm after 48 hours of experimental
      subarachnoid hemorrhage in rats.
AB  - 2-Methoxyestradiol (2ME2), a naturally occurring metabolite of estradiol, is
      known to have antiproliferative, antiangiogenic, and antiproapoptotic activities.
      Mechanistically, 2ME2 has been shown to downregulate hypoxia-inducible factor
      1alpha (HIF-1alpha). We hypothesized that hypoxia in the major cerebral arteries
      might activate a unique signaling pathway, hypoxia-inducible factor-1alpha (HIF
      1alpha), to produce or enhance cerebral vasospasm after subarachnoid hemorrhage
      (SAH). Sprague-Dawley male rats (n = 70) were randomly divided into 5 groups:
      Sham operated, SAH without treatment, SAH treated with vehicle (DMSO), SAH
      treated with two HIF-1alpha inhibitors, 2ME2, and D609 (positive control of
      2ME2). SAH model was produced by middle cerebral artery perforation. 2ME2 and
      D609 were administered intraperitoneal at 1 h after SAH; rats were sacrificed
      after 48 h of SAH. Thick blood clot was observed around basilar artery under
      arachnoids in all animals except Sham group; severe morphological vasospasm was
      observed in basilar arteries in SAH and SAH+DMSO rats, and the mild vasospasm in
      rats treated with 2ME2 and D609; 2ME2 and D609 reduced the activity of HIF-1alpha
      in the basilar arteries by HIF-1alpha DuoSet ELISA; reduce the expression of HIF
      1alpha, VEGF, BNIP3 and PCNA in basilar arteries by Western blotting and
      immunohistochemical staining. In addition, it decreased the mortality and
      improved the neurological deficits. In conclusion, 2ME2 is a powerful agent to
      reduce cerebral vasospasm by inhibiting HIF-1alpha activity and the expression of
      VEGF as its downstream, suppressing endothelium and VSMCs apoptosis via BNIP3
      pathway, and attenuating vasoproliferation.

PMID- 16904110
TI  - Nitric oxide reacts with the ferryl-oxo catalytic intermediate of the CuB-lacking
      cytochrome bd terminal oxidase.
AB  - Cytochrome bd is a bacterial respiratory oxidase carrying three hemes but no
      copper. We show that nitric oxide (NO) reacts with the intermediate F of
      cytochrome bd from Azotobacter vinelandii: (i) with a 1:1 stoichiometry, (ii)
      rapidly (k=1.2 +/- 0.1 x 10(5)M(-1)s(-1) at 20 degrees C), and (iii) yielding the
      oxidized enzyme with nitrite bound to heme d at the active site. Unexpectedly,
      the NO reaction mechanism of this catalytic intermediate in the Cu(B)-lacking
      cytochrome bd appears similar to that of beef heart cytochrome c oxidase, where
      Cu(B) was proposed to play a key role.

PMID- 16904111
TI  - Treatment of HNSCC cell lines with the EGFR-specific inhibitor cetuximab
      (Erbitux) results in paradox phosphorylation of tyrosine 1173 in the receptor.
AB  - Overexpression of the epidermal growth factor receptor (EGFR, ErbB1, HER1) is
      frequent in head and neck squamous cell carcinomas (HNSCCs) and correlates with
      disease progression. Inhibition of EGFR with the kinase inhibitor AG1478
      abolished receptor phosphorylation and reduced cell proliferation. However,
      treatment of HNSCC cells with cetuximab (Erbitux), a monoclonal antibody designed
      to block the EGFR ligand binding site, led to paradox EGFR activation due to
      hyperphosphorylation of tyrosine 1173, however, with a concomitant reduction in
      Erk1/2 phosphorylation levels. No pronounced influence on cell proliferation
      levels could be observed after treatment with this antibody. Since cetuximab
      appears able to activate EGFR in HNSCC cell lines, it is necessary to rethink the
      exact mechanisms by which cetuximab that recently was approved for the treatment
      of advanced head and neck cancer, inhibits tumor growth.

PMID- 16904112
TI  - Phosphorylation of the liver X receptors.
AB  - The liver X receptors (LXRs) function as nutritional sensors for cholesterol and
      have important roles in lipid metabolism, glucose homeostasis, and inflammation.
      We provide the first evidence that LXRs are phosphorylated proteins. Mutational
      analysis and metabolic labeling indicate LXRalpha is phosphorylated on serine 198
      in the hinge region. This is a consensus target for the MAPK family. A
      phosphorylation-deficient mutant, LXRalpha S198A, remains nuclear and responds to
      ligands like the wild-type protein. The biological significance of LXR
      phosphorylation remains to be elucidated but could provide a novel mechanism for
      the regulation of LXR signaling pathways and cellular metabolism.

PMID- 16904113
TI  - Characterization of cyclic adenine dinucleotide phosphate ribose levels in human
      spermatozoa.
AB  - OBJECTIVE: To determine the presence of the Ca2+-releasing pyridine nucleotide
      derivative, cyclic adenine dinucleotide phosphate ribose (cADPR), in human
      spermatozoa and to investigate its role in progesterone-induced Ca2+ oscillations
      in spermatozoa. DESIGN: Biochemical investigation on human spermatozoa from
      healthy volunteers. SETTING: Healthy volunteers in an academic research
      environment. PATIENT(S): Ten volunteers. INTERVENTION(S): None. MAIN OUTCOME
      MEASURE(S): The cADPR levels. RESULT(S): Human spermatozoa contain micromolar
      concentrations of cADPR that do not change significantly during sperm
      capacitation. An active synthetic machinery for cADPR is present in human
      spermatozoa, whereas degradation activity is minimal. Although progesterone
      induced Ca2+ oscillations are dependent on the ryanodine receptor, they are
      unaffected by cADPR antagonists. CONCLUSION(S): It appears that cADPR does not to
      play a role in Ca2+ oscillations in spermatozoa, but the presence of high
      concentrations of cADPR suggests that, instead, it may be introduced into the egg
      at fertilization and play a role in the Ca2+ transient immediately following
      sperm-egg fusion.

PMID- 16904114
TI  - Gonadotropin-releasing hormone antagonists do not influence the secretion of
      steroid hormones but affect the secretion of vascular endothelial growth factor
      from human granulosa luteinized cell cultures.
AB  - OBJECTIVE: To evaluate the secretion of E(2), P, and vascular endothelial growth
      factor (VEGF) in human granulosa luteinized cell cultures with the presence of a
      gonadotropin-releasing hormone (GnRH) agonist or antagonist. DESIGN: In vitro
      cell culture study. SETTING: Research laboratory of a university hospital.
      PATIENTS: Granulosa luteinized cells were obtained from 24 patients undergoing
      ovarian stimulation for IVF treatment. INTERVENTIONS: Granulosa cells were
      cultured for 48 hours with 1 nM of cetrorelix or leuprorelide. For a further 48
      hours, granulosa cells were cultured with or without the combination of
      cetrorelix plus leuprorelide. MAIN OUTCOMES: At the end of each culturing period,
      the concentrations of E(2), P, and VEGF were measured in culture supernatants by
      immunoassays. RESULTS: Estradiol and P concentrations were similar between the
      culture supernatants from controls and treatment groups. The VEGF concentrations
      in supernatants from cultures with cetrorelix (2,315.1 +/- 1,565.5 pg/mL) were
      moderately, but significantly, lower than in controls (2,604.3 +/- 1,907.1 pg/mL)
      or cultures with leuprorelide (2,558.8 +/- 1,403.1 pg/mL). CONCLUSIONS: The GnRH
      analogues do not affect steroidogenesis in human granulosa luteinized cell
      cultures. The GnRH antagonists moderately affect the secretion of VEGF from human
      granulosa luteinized cells.

PMID- 16904115
TI  - Long-term review of five leg replantations: emergency strategy and examples of
      lengthening of the leg on nerve regeneration.
AB  - The success rate for leg replantation has improved with the development of
      shortening-lengthening protocols. We checked whether this success was maintained
      long term in five cases of emergency reimplantation. The significant initial
      shortening of 93 mm, on average, enabled direct internal osteosynthesis,
      secondary lengthening was initiated swiftly, in the proximal metaphyseal area,
      and average lengthening was 85 mm. Consolidation was achieved in all cases within
      normal time periods, with an average inequality in residual length of 8mm. The
      speed of nerve regeneration was on average 1.926 mm/day, twice faster than usual
      after simple nerve suturing. At average follow-up of more than 11 years, all
      patients were walking. We conclude that nerve lengthening stimulates nerve
      regeneration, and that the results of this protocol, involving extensive initial
      debridement compensated by secondary lengthening, have enabled the limitations on
      unilateral leg replantation to be reduced.

PMID- 16904116
TI  - Association between serum albumin, carotid atherosclerosis, and metabolic
      syndrome in Japanese individuals.
AB  - Serum albumin is a maker of nutritional status and possesses antioxidative
      properties. Here, we have sought to investigate the mode of association between
      serum albumin levels, metabolic syndrome, and carotid atherosclerosis by
      analyzing the data of the cross-sectional data from 8143 individuals who
      underwent general health screening test. After adjusting for age, total
      cholesterol, and smoking status, the highest quartile of serum albumin (>or=4.7
      g/dL) was associated with increased prevalence of metabolic syndrome with an odds
      ratio of 1.80 (95% CI 1.41-2.23, P<0.0001) in women, and 1.60 (95% CI 1.44-1.78,
      P<0.0001) in men, when compared to the lowest serum albumin quartile (<4.3g/dL).
      By contrast, when compared with the lowest quartile, the highest quartile of
      serum albumin was associated with reduced prevalence of carotid plaque with an
      odds ratio of 0.62 (95% CI 0.42-0.91, P<0.001) in women, and 0.76 (95% CI 0.62
      0.93, P<0.01) in men, and for carotid intima-media thickening with an odds ratio
      of 0.57 (95% CI 0.35-0.94, P<0.05) in women, and 0.71 (95% CI 0.55-0.92, P<0.01)
      in men. Our data showed that higher serum albumin was inversely associated with
      the prevalence of early carotid atherosclerosis, although it was positively
      associated with the prevalence of metabolic syndrome. Whether these observations
      are in part explained by the antioxidative properties of albumin requires further
      investigation.

PMID- 16904117
TI  - Computational investigation of subject-specific cerebrospinal fluid flow in the
      third ventricle and aqueduct of Sylvius.
AB  - The cerebrospinal fluid flow in the third ventricle of the brain and the aqueduct
      of Sylvius was studied using computational fluid dynamics (CFD) based on subject
      specific boundary conditions derived from magnetic resonance imaging (MRI) scans.
      The flow domain geometry was reconstructed from anatomical MRI scans by manual
      image segmentation. The movement of the domain boundary was derived from MRI
      brain motion scans. Velocimetric MRI scans were used to reconstruct the velocity
      field at the inferior end of the aqueduct of Sylvius based on the theory of
      pulsatile flow in pipes. A constant pressure boundary condition was assigned at
      the foramina of Monro. Three main flow features were observed: a fluid jet
      emerging from the aqueduct of Sylvius, a moderately mobile recirculation zone
      above the jet and a mobile recirculation below the jet. The flow in the entire
      domain was laminar with a maximum Reynolds number of 340 in the aqueduct. The
      findings demonstrate that by combining MRI scans and CFD simulations, subject
      specific detailed quantitative information of the flow field in the third
      ventricle and the aqueduct of Sylvius can be obtained.

PMID- 16904118
TI  - New fractionation scheme for lipid classes based on "in-cell fractionation" using
      sequential pressurized liquid extraction.
AB  - A new preparation scheme is proposed to fractionate neutral lipids
      (acylglycerines, sterol esters, long-chain free fatty acids) from polar
      phospholipids in biological matrices. This fractionation is mandatory in the
      microbial community, for the control of bioremediation processes, in the study of
      phytoplankton growth in lakes and rivers, and in the quality control of processed
      food. Basically, a two-step pressurized liquid extraction (PLE) scheme is
      combined with an "in-cell-fractionation" using silica-based sorbents placed at
      the outlet of the PLE cartridge. The optimized extraction scheme consists of n
      hexane/acetone (9:1, v/v) extraction at 50 degrees C (2 cycles, 10 min each) to
      obtain neutral lipids followed by chloroform/methanol (1:4, v/v) extraction at
      110 degrees C (2 cycles, 10 min each). Thermally pre-treated silicic acid and
      cyanoproyl-modified silica turned out to be appropriate sorbents to ensure clear
      cut boundaries between neutral lipids and phospholipids. The proposed protocol is
      superior to commonly used approaches consisting of an exhaustive lipid extraction
      followed by off-line lipid fractionation using solid-phase extraction (SPE)
      regarding fractionation efficiency, time and solvent consumption. In this paper,
      it is also shown that the transmethylation using trimethylchlorosilane/methanol
      (1:9, v/v) provides a complete reaction to give methyl esters without artefact
      formation across the array of different lipid classes even with polyunsaturated
      fatty acid moieties.

PMID- 16904119
TI  - Simultaneous determination of methyl tert-butyl ether, its degradation products
      and other gasoline additives in soil samples by closed-system purge-and-trap gas
      chromatography-mass spectrometry.
AB  - A new protocol for the simultaneous determination of methyl tert-butyl ether
      (MTBE); its main degradation products: tert-butyl alcohol (TBA) and tert-butyl
      formate (TBF); other gasoline additives, oxygenate dialkyl ethers: ethyl tert
      butyl ether (ETBE), tert-amyl methyl ether (TAME) and diisopropyl ether (DIPE);
      aromatics: benzene, toluene, ethylbenzene and xylenes (BTEX) and other compounds
      causing odour events such as dicyclopentadiene (DCPD) and trichloroethylene (TCE)
      in soils has been developed. On the basis of US Environmental Protection Agency
      (EPA) method 5035A, a fully automated closed-system purge-and-trap coupled to gas
      chromatography/mass spectrometry (P&T-GC/MS) was optimised and permitted to
      detect microg/kg concentrations in solid matrices avoiding losses of volatile
      compounds during operation processes. Parameters optimised were the sampling
      procedure, sample preservation and storage, purging temperature, matrix effects
      and quantification mode. Using 5 g of sample, detection limits were between 0.02
      and 1.63 microg/kg and acceptable method precision and accuracy was obtained
      provided quantification was performed using adequate internal standards. Soil
      samples should be analysed as soon as possible after collection, stored under -15
      degrees C for not longer than 7 days if degradation products have to be analysed.
      The non-preservative alternative (empty vial) provided good recoveries of the
      most analytes when freezing the samples up to 7 day holding time, however, if
      biologically active soil are analysed the preservation with trisodium phosphate
      dodecahydrate (Na(3)PO(4).12H(2)O or TSP) is strongly recommended more than
      sodium bisulphate (NaHSO(4)). The method was finally applied to provide threshold
      and background levels of several gasoline additives in a point source and in
      sites not influenced by gasoline spills. The proposed method provides the
      directions for the future application on real samples in current monitoring
      programs at gasoline pollution risk sites where till now little monitoring data
      for MTBE in soils are available.

PMID- 16904120
TI  - Comparison of an acetonitrile extraction/partitioning and "dispersive solid-phase
      extraction" method with classical multi-residue methods for the extraction of
      herbicide residues in barley samples.
AB  - An acetonitrile/partitioning extraction and "dispersive solid-phase extraction
      (SPE)" method that provides high quality results with a minimum number of steps
      and a low solvent and glassware consumption was published in 2003. This method,
      suitable for the analysis of multiple classes of pesticide residues in foods, has
      been given an acronymic name, QuEChERS, that reflects its major advantages
      (quick, easy, cheap, effective, rugged, safe). In this work, QuEChERS method,
      which was originally created for vegetable samples with a high amount of water,
      was modified to optimise the extraction of a wide range of herbicides in barley.
      Then, it was compared with known conventional multi-residue extraction procedures
      such as the Luke method, which was simplified and shortened by eliminating the
      Florisil clean-up (mini Luke) and the ethyl acetate extraction, which involves a
      subsequent clean-up by gel permeation chromatography (GPC) and which is the
      official extraction method used by some of European authorities. Finally, a
      simple acetone extraction was carried out to check the differences with the other
      three methods. Extracts were analysed by gas chromatography-time-of-flight mass
      spectrometry (GC-TOF/MS) and liquid chromatography-tandem mass spectrometry (LC
      MS/MS). Mini Luke was significantly more effective for the extraction of non
      polar and medium-polar compounds, but the best recoveries for polar compounds
      were achieved by QuEChERS and ethyl acetate methods. QuEChERS was the only method
      that provided an overall recovery value of 60-70% for non-, medium- and polar
      compounds, with some exceptions due to co-eluted matrix interferences. Clean-up
      by dispersive SPE was effective and did not differ so much with ethyl acetate
      extracts considering that QuEChERS clean-up step is much easier and less time
      consuming. As a conclusion, it resulted to be the most universal extraction
      method by providing a well-defined phase separation without dilution and
      achieving acceptable recoveries in average including the extraction of the always
      difficult acidic herbicides. However, recoveries were not as good as required for
      validation purposes suggesting that residues are prone to strong matrix
      interactions in dry samples as barley and further method adaptation incrementing
      solvent strength, extraction time or more acidic or basic conditions is needed in
      order to achieve a complete extraction.

PMID- 16904121
TI  - Theoretical study of the acid-base properties of the montmorillonite/electrolyte
      interface: influence of the surface heterogeneity and ionic strength on the
      potentiometric titration curves.
AB  - The parallel shape of the potentiometric titration curves for montmorillonite
      suspension is explained using the surface complexation model and taking into
      account the surface heterogeneity. The homogeneous models give accurate
      predictions only if they assume unphysically large values of the equilibrium
      constants for the exchange process occurring on the basal plane. However, the
      assumption that the basal plane is energetically heterogeneous allows to fit the
      experimental data (reported by Avena and De Pauli [M. Avena, C.P. De Pauli, J.
      Colloid Interface Sci. 202 (1998) 195-204]) for reasonable values of exchange
      equilibrium constant equal to 1.26 (suggested by Fletcher and Sposito [P.
      Fletcher, G. Sposito, Clay Miner. 24 (1989) 375-391]). Moreover, we observed the
      typical behavior of point of zero net proton charge (pznpc) as a function of
      logarithm of the electrolyte concentration (log[C]). We showed that the slope of
      the linear dependence, pznpc=f(log[C]), is proportional to the number of
      isomorphic substitutions in the crystal phase, which was also observed in the
      experimental studies.

PMID- 16904122
TI  - Preschoolers' use of surface similarity in object comparisons: taking context
      into account.
AB  - Previous research has emphasized the role of within-match similarity in
      children's comparisons. The current study investigated another potentially
      important contributing factor, namely the distinctiveness of the matching items
      relative to other items in the scene. Using a well-known relational mapping task,
      we found that 3- and 4-year-olds made more correct matches between identical
      objects when those objects were maximally distinctive from the foils. In a cross
      mapping experiment, where same relative size was pitted against object
      similarity, 3-year-olds made more incorrect object matches when the objects were
      both similar to each other and distinctive from the foils. Furthermore, 3- and 4
      year-olds performed the same, regardless of within-match similarity, so long as
      the ratios of within-match and nonmatch similarity were roughly equal. These
      findings suggest that children's comparisons are guided by a ratio consisting of
      many pairwise similarity relations, including (but not limited to) the degree of
      within-match similarity.

PMID- 16904123
TI  - Orthographic learning via self-teaching in children learning to read English:
      effects of exposure, durability, and context.
AB  - This experiment investigated orthographic learning via self-teaching in 8- and 9
      year-olds learning to read English. Children were exposed to novel words, and
      following a 1- or 7-day delay interval, orthographic learning was assessed by
      asking children to select previously seen novel words from an array of visually
      and phonologically similar foils. Novel words were exposed either in meaningful
      text or in isolation, and number of exposures was manipulated with each novel
      word appearing once, twice, or four times. Learning increased as a function of
      number of exposures, although some evidence of durable one-trial learning was
      observed. Context played no role, suggesting that orthographic learning is not
      dependent on meaning-based information. In general, these findings offer support
      for the central aspects of Share's self-teaching hypothesis. However, although we
      observed a general relation between phonological decoding and orthographic
      learning, the relation did not hold at an item-by-item level of analysis,
      suggesting that a strong version of Share's item-based account is not correct.

PMID- 16904124
TI  - Secreted protein-based reporter systems for monitoring inflammatory events:
      critical interference by endoplasmic reticulum stress.
AB  - A number of recent reports have used secreted protein-based reporter assays for
      monitoring intercellular and intracellular events involved in inflammation.
      However, we found that these assay systems are critically affected by endoplasmic
      reticulum (ER) stress. When reporter mesangial cells that express secreted
      alkaline phosphatase (SEAP) under the control of NF-kappaB were exposed to IL
      1beta or TNF-alpha, induction of SEAP activity was markedly reduced under ER
      stress conditions. Downregulation of SEAP activity was observed regardless of
      cell types and type of regulatory elements; e.g., when reporter hepatocytes that
      express SEAP under the control of the dioxin responsive elements were exposed to
      2,3,7,8-tetrachlorodibenzo-p-dioxin or benzo[a]pyrene, ER stress similarly
      suppressed the increase in SEAP activity despite its transcriptional
      upregulation. Activity of constitutively expressed SEAP in various cells was also
      reduced by ER stress in a magnitude-dependent manner, and it was associated with
      disturbed subcellular transport of SEAP to the Golgi. Furthermore, interference
      by ER stress was similarly observed in other reporter assay using secreted
      luciferase. These results evidenced critical interference by ER stress in
      secreted protein-based reporter systems. The suppression of reporter responses by
      ER stress should be considered carefully for experimental design and
      interpretation of data when secreted protein-based reporter systems are used for
      investigation.

PMID- 16904125
TI  - Re-examining sustained attention deficits as vulnerability indicators for
      schizophrenia: stability in the long term course.
AB  - This study examined the longitudinal patterns in the sustained attention deficits
      detected by the Continuous Performance Test (CPT) and the factors influencing
      such changes in consecutively admitted schizophrenia patients (n=224) followed up
      for 4-7 year. Exploratory growth mixture modeling analyses of subjects' CPT
      performances over successive follow-ups revealed that three major (accounting for
      92.8%) plus one minor subgroups could be delineated. Subgrouping was then
      performed on a subsample of 104 subjects who had at least 3 times of CPT data.
      Based on subjects' adjusted z score of the test sensitivity index d' derived from
      comparing with a community sample, patients were divided into three subgroups: no
      impairment (-1), moderate impairment (-2.5 to -1), and severe impairment (< 
      2.5). The trajectory taken by individual patient was analyzed according to the
      initial subgroup status and subsequent changes, controlling for relevant basic
      and clinical characteristics. Both growth mixture modeling and subgroup status
      analyses found that around one third of those with severe impairment at baseline
      showed persistent severe impairment. Those with no impairment were stable and
      exhibited least tendency for further performance deterioration. Those with
      moderate impairment tended to fluctuate markedly, mainly towards the better
      rather than the worse. Previous subgrouping status and concurrent task-taking
      strategy predicted the performance subgroup status at follow-ups, while clinical
      symptoms and disease course factors did not. We concluded that there is
      substantial heterogeneity in schizophrenia patients' long term pattern in
      sustained attention deficits and those with severe impairment might represent a
      subgroup with stable vulnerability to schizophrenia.

PMID- 16904126
TI  - Reduction in the motor unit number estimate (MUNE) after cerebral infarction.
AB  - BACKGROUND: The mechanism of the decrease in motor unit number estimates (MUNEs)
      after cerebral infarction has not been studied systematically. We examined the
      relationship between the degree to which MUNEs decreased and the other clinical
      features of patients with the infarction. METHODS: Using a multiple point
      stimulation technique, we obtained the MUNE of the hypothenar muscle group in 13
      age-matched control subjects and 30 patients with cerebral infarction. In all
      patients, we obtained the Japan Stroke Scale (JSS) and head MR images. In eight
      patients with acute cerebral infarction, admitted within 24 h after onset, we
      also obtained head MR angiograms and single-photon emission CT. FINDINGS: There
      was a decrease in the MUNE of the hypothenar muscle group on the affected side of
      24 patients with cerebral infarction and hand weakness. The decrease in the MUNE
      started from 4 to 30 h after the infarction, when T1-weighted MR images of the
      brain involved were normal. The degree to which the MUNE decreased correlated
      with the part of the JSS showing the upper extremity weakness. INTERPRETATIONS: A
      decrease in the MUNE of the hypothenar muscle group within 30 h after cerebral
      infarction may be due to trans-synaptic inhibition of the spinal alpha motor
      neurons innervating this muscle.

PMID- 16904127
TI  - Localized colonic inflammation increases cytokine levels in distant small
      intestinal segments in the rat.
AB  - Local inflammation in the colon has been associated with nutrient malabsorption
      and altered motility in the small bowel. These remote effects suggest the release
      of mediators which can act (or alter) the function of intestinal segments located
      far from the primary area of inflammation. This study describes the changes in
      the expression of pro-inflammatory cytokines in the colon and in various segments
      of the small intestine in two rat models of experimental colitis. Colitis was
      induced by the intracolonic administration of 100 microL of 6% iodoacetamide or
      250 microL of 2, 4, 6-trinitrobenzene sulfonic acid. Levels of interleukin one
      beta, interleukin 6, and tumor necrosis factor alpha were measured by ELISA in
      tissue homogenate sampled from duodenum, jejunum, ileum and colon at different
      time intervals. In homogenates of strips isolated from duodenum, jejunum and
      ileum, tumor necrosis alpha and interleukin-6, increased significantly 3-6 h
      after iodoacetamide or TNBS administration and remained elevated until the
      colonic inflammation subsided. Interleukin one beta showed comparable but delayed
      increase. Similar, but more pronounced increase of the three cytokines was
      noticed in areas of the colon adjacent to the ulcer. Histologic examinations
      revealed important inflammatory changes in the colon; however, examination of
      sections from the small intestines did not reveal significant differences between
      controls and rats with colitis. In conclusion, expression of pro-inflammatory
      cytokines is increased in remote segments of the small intestines during colitis.
      The findings may provide a partial explanation or a molecular substrate for the
      associated small bowel dysfunction.

PMID- 16904128
TI  - Mechanisms of the acute ischemia-induced arrhythmogenesis--a simulation study.
AB  - The underlying ionic mechanisms of ischemic-induced arrhythmia were studied by
      the computer simulation method. To approximate the real situation, ischemic cells
      were simulated by considering the three major component conditions of acute
      ischemia (elevated extracellular K(+) concentration, acidosis and anoxia) at the
      level of ionic currents and ionic concentrations, and a round ischemic zone was
      introduced into a homogeneous healthy sheet to avoid sharp angle of the ischemic
      tissue. The constructed models were solved using the operator splitting and
      adaptive time step methods, and the perturbation finite difference (PFD) scheme
      was first used to integrate the partial differential equations (PDEs) in the
      model. The numerical experiments showed that the action potential durations
      (APDs) of ischemic cells did not exhibited rate adaptation characteristic,
      resulting in flattening of the APD restitution curve. With reduction of sodium
      channel availability and long recovery of excitability, refractory period of the
      ischemic tissue was significantly prolonged, and could no longer be considered as
      same as APD. Slope of the conduction velocity (CV) restitution curve increased
      both in normal and ischemic region when pacing cycle length (PCL) was short, and
      refractory period dispersion increased with shortening of PCL as well. Therefore,
      dynamic changes of CV and dispersion of refractory period rather than APD were
      suggested to be the fundamental mechanisms of arrhythmia in regional ischemic
      myocardium.

PMID- 16904129
TI  - Branching stochastic processes with immigration in analysis of renewing cell
      populations.
AB  - This paper considers the utility of a new class of stochastic branching processes
      with non-homogeneous immigration in modeling complex renewing cell systems. Such
      systems typically include the population of stem cells that provides an
      inexhaustible supply of cells necessary for maintaining the cellular composition
      of a tissue. A stem cell may be induced to transform (differentiate) into a
      progenitor cell. Progenitor cells retain the ability to proliferate and their
      function is believed to provide a quick proliferative response to an increased
      demand for cells in the population. There may be several sub-types of progenitor
      cells. Terminally differentiated cells do not divide under normal conditions;
      they are responsible for maintaining tissue-specific functions. Recent
      advancements in experimental techniques offer considerable scope for quantitative
      studies of in vivo cell kinetics based on stochastic modeling of renewing cell
      populations. However, no ready-made theory is currently available to take full
      advantage of these advancements. This paper introduces such a theory with a
      special focus on its feasibility in biological applications.

PMID- 16904130
TI  - Effects of transmural electrical heterogeneities and electrotonic interactions on
      the dispersion of cardiac repolarization and action potential duration: A
      simulation study.
AB  - It has been shown in the literature that myocytes isolated from the ventricular
      walls at various intramural depths have different action potential durations
      (APDs). When these myocytes are embedded in the ventricular wall, their
      inhomogeneous properties affect the sequence of repolarization and the actual
      distribution of the APDs in the entire wall. In this article, we implement a
      mathematical model to simulate the combined effect of (a) the non-homogeneous
      intrinsic membrane properties (in particular the non-homogeneous APDs) and (b)
      the electrotonic currents that modulate the APDs when the myocytes are embedded
      in the ventricular myocardium. In particular, we study the effect of (a) and (b)
      on the excitation and repolarization sequences and on the distribution of APDs in
      the ventricles. We implement a Monodomain tissue representation that includes
      orthotropic anisotropy, transmural fiber rotation and homogeneous or
      heterogeneous transmural intrinsic membrane properties, modeled according to the
      phase I Luo-Rudy membrane ionic model. Three-dimensional simulations are
      performed in a cartesian slab with a parallel finite element solver employing
      structured isoparametric trilinear finite elements in space and a semi-implicit
      adaptive method in time. Simulations of excitation and repolarization sequences
      elicited by epicardial or endocardial pacing show that in a homogeneous slab the
      repolarization pathways approximately follow the activation sequence. Conversely,
      in the heterogeneous cases considered in this study, we observed two
      repolarization wavefronts that started from the epi and the endocardial faces
      respectively and collided in the thickness of the wall and in one case an
      additional repolarization wave starting from an intramural site. Introducing the
      heterogeneities along the transmural epi-endocardial direction affected both the
      repolarization sequence and the APD dispersion, but these effects were clearly
      discernible only in transmural planes. By contrast, in planes parallel to epi-
      and endocardium the APD distribution remained remarkably similar to that observed
      in the homogeneous model. Therefore, the patterns of the repolarization sequence
      and APD dispersion on the epicardial surface (or any other intramural surface
      parallel to it) do not reveal the uniform transmural heterogeneity.

PMID- 16904131
TI  - Phase transition as a mechanism of DNA opening for replication and transcription.
AB  - We propose a dynamic model of DNA opening for replication and transcription.
      Numerical simulations on this model strongly indicate a phase transition
      mechanism of DNA opening.

PMID- 16904133
TI  - Using the tangle: a consistent construction of phylogenetic distance matrices for
      quartets.
AB  - Distance based algorithms are a common technique in the construction of
      phylogenetic trees from taxonomic sequence data. The first step in the
      implementation of these algorithms is the calculation of a pairwise distance
      matrix to give a measure of the evolutionary change between any pair of the
      extant taxa. A standard technique is to use the log det formula to construct
      pairwise distances from aligned sequence data. We review a distance measure valid
      for the most general models, and show how the log det formula can be used as an
      estimator thereof. We then show that the foundation upon which the log det
      formula is constructed can be generalized to produce a previously unknown
      estimator which improves the consistency of the distance matrices constructed
      from the log det formula. This distance estimator provides a consistent technique
      for constructing quartets from phylogenetic sequence data under the assumption of
      the most general Markov model of sequence evolution.

PMID- 16904132
TI  - Convergence results for contact branching processes.
AB  - The link between the multi-type contact birth process and the spatial
      deterministic S-->I epidemic is exploited to give convergence results for a multi
      type Markovian contact branching process. Let U(t) be the position of furthest
      spread by time t in a specific direction. The asymptotic speed of translation of
      the distribution function of U(t) is derived and U(t)/t is shown to converge in
      probability to this speed.

PMID- 16904134
TI  - Congruent epidemic models for unstructured and structured populations: analytical
      reconstruction of a 2003 SARS outbreak.
AB  - Both the threat of bioterrorism and the natural emergence of contagious diseases
      underscore the importance of quantitatively understanding disease transmission in
      structured human populations. Over the last few years, researchers have advanced
      the mathematical theory of scale-free networks and used such theoretical
      advancements in pilot epidemic models. Scale-free contact networks are
      particularly interesting in the realm of mathematical epidemiology, primarily
      because these networks may allow meaningfully structured populations to be
      incorporated in epidemic models at moderate or intermediate levels of complexity.
      Moreover, a scale-free contact network with node degree correlation is in accord
      with the well-known preferred mixing concept. The present author describes a semi
      empirical and deterministic epidemic modeling approach that (a) focuses on time
      varying rates of disease transmission in both unstructured and structured
      populations and (b) employs probability density functions to characterize disease
      progression and outbreak controls. Given an epidemic curve for a historical
      outbreak, this modeling approach calls for Monte Carlo calculations (that define
      the average new infection rate) and solutions to integro-differential equations
      (that describe outbreak dynamics in an aggregate population or across all network
      connectivity classes). Numerical results are obtained for the 2003 SARS outbreak
      in Taiwan and the dynamical implications of time-varying transmission rates and
      scale-free contact networks are discussed in some detail.

PMID- 16904135
TI  - Neuropeptide Y and corticotropin-releasing factor bi-directionally modulate
      inhibitory synaptic transmission in the bed nucleus of the stria terminalis.
AB  - Neuropeptide Y (NPY) and corticotropin-releasing factor (CRF) have opposing
      effects on stress and anxiety. Both can modify synaptic activity through their
      binding to NPY receptors (YRs) and CRF receptors (CRFRs) respectively. The bed
      nucleus of the stria terminalis (BNST) is a brain region with enriched expression
      of both NPY and YRs and CRF and CRFRs. A component of the "extended amygdala",
      the BNST is anatomically well-situated to integrate stress and reward-related
      processing in the CNS, regulating activation of the hypothalamic-pituitary
      adrenal (HPA) axis and reward circuits. Using whole-cell recordings in a BNST
      slice preparation, we found that NPY and CRF inhibit and enhance GABAergic
      transmission, respectively. Pharmacological experiments suggest that NPY
      depresses GABAergic transmission through activation of the Y2 receptor (Y2R),
      while both pharmacological and genetic experiments suggest that CRF and urocortin
      enhance GABAergic transmission through activation of the CRF receptor 1 (CRFR1).
      Further, the data suggest that NPY acts to regulate GABA release, while CRF
      enhances postsynaptic responses to GABA. These results suggest potential
      anatomical and cellular substrates for the robust behavioral interactions between
      NPY and CRF.

PMID- 16904136
TI  - Haptic orientation perception: sex differences and lateralization of functions.
AB  - The present study examined sex differences in haptic orientation representation
      using three tasks: a bimanual parallel-setting task comprising haptic orientation
      perception and motor matching action, and two unimanual tasks focusing on the
      perception and action elements separately. A verbal judgment task focused on
      haptic orientation perception: participants were to assign a number of minutes to
      a felt orientation. An orientation production task required the rotation of a bar
      to match a verbally presented number of minutes. Although both male and female
      performance was systematically biased we found that males are more accurate in
      parallel-setting and verbal judgment of orientation, suggesting differences in
      haptic orientation perception, in particular. Increasing allocentric reference
      frame involvement by delaying the action in the parallel-setting task did not
      affect the sex difference found. In addition to a male advantage over tasks,
      performance on both unimanual tasks suggests sex differences in lateralization of
      haptic orientation processing; a dependence on hand orientation was found only
      for right hand performance in males.

PMID- 16904137
TI  - Validation of a behavioral observation tool to assess pig welfare.
AB  - Accurately measuring and monitoring of animal behavior is an important factor
      when assessing on-farm animal welfare. First we developed a feasible and simple
      method aiming at consistently on-farm measuring of pig's behavior. This test
      should cover a broad range of welfare-related pig behavior. The reaction towards
      a novel object, startling, tail and ear biting, play and aggressive behavior,
      stereotypies, coughing, sneezing, skin lesions, defecation, urination and
      cleanliness of body and pen are included. The development of accurate measures of
      on-farm behavior first requires the reliability assessment of the procedure.
      Therefore, the methodology was tested in a first part by three observers scoring
      simultaneously and independently pre-defined behavioral characteristics of 108
      group-housed fattening pigs. The inter-observer repeatability of the measures was
      calculated using intraclass correlation coefficients, which ranged from 0.7 to 1.
      In a second part, the objective was to validate the behavioral characteristics
      against salivary cortisol, urinary epinephrine and norepinephrine and production
      traits. Salivary cortisol concentrations significantly increased in ear-bitten
      pigs and in pigs with tail lesions. Growth rate significantly dropped when
      cortisol levels rose. An age effect was also found. The percentage of animals
      approaching the novel object is positively correlated with the urinary
      epinephrine concentration. Pigs defecating during the test showed significantly
      higher epinephrine levels. Urinary norepinephrine concentration decreased
      significantly with age. Faster growing animals and animals with tail lesions
      showed significantly higher levels of norepinephrine. Pen dirtiness and number of
      animals per pen were associated with higher norepinephrine concentrations.
      Finally, barrows had higher norepinephrine concentrations than sows.

PMID- 16904139
TI  - The blood-brain barrier as a regulatory interface in the gut-brain axes.
AB  - The blood-brain barrier (BBB) prevents the unrestricted movement of peptides and
      proteins between the brain and blood. However, some peptides and regulatory
      proteins can cross the BBB by saturable and non-saturable mechanisms. Leptin and
      insulin each cross the BBB by their own transporters. Impaired transport of
      leptin occurs in obesity and accounts for peripheral resistance; that is, the
      condition wherein an obese animal loses weight when given leptin directly into
      the brain but not when given leptin peripherally. Leptin transport is also
      inhibited in starvation and by hypertriglyceridemia. Since hypertriglyceridemia
      occurs in both starvation and obesity, we have postulated that the peripheral
      resistance induced by hypertriglyceridemia may have evolved as an adaptive
      mechanism in response to starvation. Insulin transport is also regulated. For
      example, treatment of mice with lipopolysaccharide (LPS) increases insulin
      transport across the BBB by about threefold. Since many of the actions of CNS
      insulin oppose those of peripheral insulin and since LPS releases proinflammatory
      cytokines, enhanced transport of insulin across the BBB could be a mechanism
      which promotes insulin resistance in sepsis. The brain endothelial cells which
      comprise the BBB secrete many substances including cytokines. Such secretion can
      be stimulated from one side of the BBB with release into the other side. For
      example, it appears that adiponectin can inhibit release of interleukin-6 from
      brain endothelial cells. Overall, the BBB represents an important interface in
      mediating gut-brain axes.

PMID- 16904138
TI  - Effect of flavour of liquid Ensure diet supplement on energy intake in male SD
      rats.
AB  - Outbred male Sprague-Dawley rats were provided with one of the four flavours of
      the liquid diet, Ensure, in addition to chow pellets, to examine whether
      differences in flavour lead to differences in energy intake i.e. degree of over
      consumption. For half the rats, the Ensure supplement was provided for 14 days
      and then withdrawn for the final 8 days of the study, whereas the remaining
      animals were allowed to consume Ensure for 22 days. All four flavours of Ensure,
      chocolate, vanilla, coffee and asparagus, induced a sustained increase in daily
      energy intake of approximately 15%. There was an effect of flavour on initial
      consumption of the Ensure diet, with coffee and asparagus flavours being consumed
      less avidly than vanilla or chocolate. However, this effect was short-lived.
      Overall, there was no effect of flavour on body weight gain, energy intake from
      Ensure, total energy intake, body composition, or measured blood hormones and
      metabolites. Withdrawal of Ensure resulted in reductions in body weight gain,
      total energy intake, fat but not lean tissue mass, and concentrations of blood
      leptin, non-esterified fatty acids and triglycerides, but there was no effect of
      the flavour of Ensure previously supplied on any of these parameters. The ability
      of the liquid diet, Ensure, to stimulate long-term caloric over-consumption is
      not due to its flavouring. Rather, other attributes of Ensure must be more
      important, such as its intrinsic flavour, liquid formulation, macronutrient
      composition, and ease of ingestion, digestion and absorption.

PMID- 16904140
TI  - Effects of attention and rewarded activity on immune parameters and wound healing
      in pigs.
AB  - Challenging animals with a demanding situation they are able to cope with and
      where they are rewarded may be a source of positive emotions and possibly of
      increased welfare. In order to test if this results in changes of immunological
      parameters and wound healing, 56 pigs (7-20 weeks of age), housed in groups of 8
      animals each, were successfully trained to recognize and localize an individual
      acoustic summons and to receive a small portion of feed as a reward. Immune
      reactions and the development of a standardized biopsy wound were compared to
      values of conventionally fed control groups of equal size and animal-to-feeding
      place ratio (2:1). In the experimental animals a significantly higher
      concentration of IgG as well as an increased in vitro T-cell proliferation to
      ConA but a reduced LPS-induced proliferation of B-cells was found, while basal
      salivary cortisol concentrations were similar. Wound development was better in
      the experimental animals as measured by the area of the inflammatory corona. It
      decreased more rapidly in the experimental animals since the 5th day after biopsy
      and was significantly smaller than in the control groups. We conclude that
      environmental enrichment by equipment provoking attention and cognitive activity
      which is rewarded by feed may play a beneficial role for physical welfare of
      intensively housed pigs.

PMID- 16904141
TI  - Troubles shared are troubles halved: stress in rats is reduced in proportion to
      social propinquity.
AB  - The mitigation of stress by social support is of obvious interest and widely
      studied. Animal models have been used extensively to elucidate the mechanisms
      involved. Typically, these examine the effects of social housing versus
      isolation, imparting resistance to stress before it is applied, or ameliorating
      its effects post hoc. Few experiments directly compare stress impinging upon an
      individual alone or in a social milieu. Here we compare the effects of stress on
      a solitary rat and on pairs of rats in a structured rank order of social
      propinquity. Rats were placed on a raised platform for 30 min under four
      conditions manipulating the degree of proximity between the rats: alone on the
      platform in the test room, on the platform with a cagemate in a cage elsewhere in
      the room, two rats each on a raised platform 40 cm apart and two rats each on a
      raised platform 0 cm apart. Immediately after the stress, the rats were tested in
      an open field. We find that stress is mitigated proportionally: stress was
      reduced the more salient the other rat's cues were and the closer the rats were
      to each other.

PMID- 16904142
TI  - Childhood asthma and return to school in Sydney, Australia.
AB  - OBJECTIVES: To describe the seasonal pattern of hospital admissions for childhood
      asthma in Sydney, Australia and investigate the relationship between these
      admissions and time of return to school. STUDY DESIGN: Time-series analysis of
      daily hospital admissions for childhood asthma in Sydney from 1994 to 2000.
      METHODS: We defined the time series of all asthma-related hospital admissions in
      Sydney between 1994 and 2000 for age groups 1-4 and 5-14 years. We analysed the
      time series for each age group using a generalized additive model with a log-link
      function, an offset term and quasi-likelihood estimation. Daily admissions were
      modelled using penalised regression splines adjusting for long term trends,
      school terms and holidays, weekday and influenza epidemics. RESULTS: After
      adjusting for potential confounding, the risk of asthma admission increased to a
      peak between 2 and 4 weeks after the first day of school in each term and varied
      between 1.5 and 3 times the risk prior to return to school for both age groups.
      The largest increase in asthma risk occurring in term one after the long summer
      holiday. The increase in admission risk began soon after the first day of school
      of each term for school age children 5-14 years, but not in pre-school age
      children 1-4 years. CONCLUSIONS: Returning to school after term holidays is
      strongly associated with increased risk of hospital admissions for asthma in
      children, especially following the long summer holiday. Preventive measures
      focused on return to school have the potential to substantially decrease
      admissions for asthma in children.

PMID- 16904143
TI  - A Bayesian, combinatorial approach to capture-recapture.
AB  - It is shown that, in the capture-recapture method, the widely used formulae of
      Bailey or Chapman-Seber give the most likely value for the size of the
      population, but systematically underestimate the probability that the population
      is larger than any given size. We take here a first step in a combinatorial
      approach which does not suffer from this flaw: formulae are given which can be
      used in the closed case (no birth, death or migrations between captures) when at
      least two animals have been recaptured and when there is homogeneity with regard
      to capture probability. Numerical and heuristic evidence is presented pointing to
      the fact that the error incurred when using the formulae of Bailey or Chapman
      Seber depends asymptotically only on the number of recaptured animals, and will
      not diminish if the number of captured animals becomes large while the number of
      recaptured animals remains constant. A result that was stated and left unproven
      by Darroch is proven here.

PMID- 16904144
TI  - Towards a unifying approach to diversity measures: bridging the gap between the
      Shannon entropy and Rao's quadratic index.
AB  - The diversity of a species assemblage has been studied extensively for many
      decades in relation to its possible connection with ecosystem functioning and
      organization. In this view most diversity measures, such as Shannon's entropy,
      rely upon information theory as a basis for the quantification of diversity.
      Also, traditional diversity measures are computed using species relative
      abundances and cannot account for the ecological differences between species. Rao
      first proposed a diversity index, termed quadratic diversity (Q) that
      incorporates both species relative abundances and pairwise distances between
      species. Quadratic diversity is traditionally defined as the expected distance
      between two randomly selected individuals. In this paper, we show that quadratic
      diversity can be interpreted as the expected conflict among the species of a
      given assemblage. From this unusual interpretation, it naturally follows that
      Rao's Q can be related to the Shannon entropy through a generalized version of
      the Tsallis parametric entropy.

PMID- 16904145
TI  - Depression of cardiac L-type calcium current by a scorpion venom fraction M1
      following muscarinic receptors interaction involving adenylate cyclase pathway.
AB  - The effects of a non-toxic fraction, called M1, from Buthus occitanus tunetanus
      (Bot) scorpion were studied on rat cardiac contraction and calcium transient and
      current. A decrease in both rate and tension on isolated intact hearts as well as
      in calcium transient induced by depolarizing 100 K(+) solution on isolated
      ventricular cardiomyocytes was firstly observed. Studies with the whole cell
      patch clamp method showed that M1 decreased the L-type calcium current (ICa(L))
      in a dose-dependent manner with an IC50 of 0.36 microg/mL and a Hill coefficient
      of 0.95. This effect was blocked and reversed by the specific muscarinic
      receptors antagonist atropine, 1 microM, and was completely prevented when
      cardiomyocytes were pretreated with Pertussis toxin, 1 microg/mL, to block the
      alpha subunit of the PTX-sensitive G proteins. These results show that M1
      fraction of Bot inhibits basal calcium current by interacting with muscarinic
      receptors and suggest that this inhibition could be attributed to inhibition of
      adenylate cyclase activity by a mechanism involving PTX-sensitive G proteins.

PMID- 16904146
TI  - Elastodynamic wave propagation in graded materials: simulations, experiments,
      phenomena, and applications.
AB  - A two-dimensional numerical simulation model for the elastodynamic wave
      propagation in two linear elastic, isotropic, joint half-spaces is presented. The
      border between the two half-spaced is graded in a way, that the values of the
      elastic properties and the densities vary smoothly (sinusoidally) from the values
      of one continuum to the values of the other continuum within a transition zone of
      a defined thickness. It is demonstrated, that a graded layer leads to a frequency
      and wavelength dependent refraction and reflection behavior of elastodynamic
      waves. Numerical results show that wavelengths which are long compared with the
      transition layer thickness are dominantly reflected whereas short waves are
      dominantly transmitted, a phenomena which does not occur in the case of an
      infinitely thin transition layer. Furthermore the frequency dependent reflection
      and transmission behavior of elastodynamic waves is verified experimentally.
      There the interface between two vapor deposited films is graded due to
      intermetallic diffusion effects. These graded microstructures are analyzed with a
      short-pulse-laser-acoustic set-up. The corresponding frequencies of the
      elastodynamic waves which are filtered with these functionally graded
      microstructures are in the range of 0.5 THz.

PMID- 16904147
TI  - Influence of the precision of spectral backscatter measurements on the estimation
      of scatterers size in cancellous bone.
AB  - The goal of this study is to propose a model for the ultrasonic frequency
      dependent backscatter coefficient in femoral cancellous bone. This model has been
      developed with success to predict backscatter in human calcaneal bone [Jenson,
      Ultr. Med. Biol. 2003]. A weak scattering model is used and the backscatter
      coefficient is expressed in terms of a Gaussian autocorrelation function of the
      medium. The backscatter coefficient is computed and comparison is made with
      experimental data for 37 specimens and for frequency ranging from 0.4 to 1.2 MHz.
      An excellent agreement between experimental data and predictions is found for
      both the magnitude and the frequency-dependence of the backscatter coefficient.
      Then, a nonlinear regression is performed for each specimen, and the mean
      trabecular thickness is estimated. Experimental data and theoretical predictions
      are averaged over the 37 specimens. We also find a close agreement between
      theoretical predictions obtained using the Gaussian autocorrelation function
      (scatterer size=134+/-15 microm) and the mean trabecular thickness (Tb.Th=132+/
      12 microm) derived from the analysis of bone 3-D micro-architecture using high
      resolution micro-tomography. However, the correlation between individual
      experimental and estimated Tb.Th values is moderate (R(2)=0.44). The performance
      of the estimator are limited mainly by two factors: interference noise due to
      random positioning of the scatterers and attenuation. We show that the
      fundamental limitation of our estimator due to the speckle noise is around 5
      microm for trabecular thickness estimation. This limitation is lower than the
      observed biological variability which is around 30 microm and should not be a
      limiting factor for individual prediction. A second limitation is the tremendous
      attenuation encountered in highly scattering media such as cancellous bone, which
      results in highly damped backscatter signals. The compensation for attenuation is
      difficult to perform, and it may be a critical point that limits the precision of
      the estimator.

PMID- 16904148
TI  - The small envelope protein of porcine reproductive and respiratory syndrome virus
      possesses ion channel protein-like properties.
AB  - The small envelope (E) protein of porcine reproductive and respiratory syndrome
      virus (PRRSV) is a hydrophobic 73 amino acid protein encoded in the internal open
      reading frame (ORF) of the bicistronic mRNA2. As a first step towards
      understanding the biological role of E protein during PRRSV replication, E gene
      expression was blocked in a full-length infectious clone by mutating the ATG
      translational initiation to GTG, such that the full-length mutant genomic clone
      was unable to synthesize the E protein. DNA transfection of PRRSV-susceptible
      cells with the E gene knocked-out genomic clone showed the absence of virus
      infectivity. P129-DeltaE-transfected cells however produced virion particles in
      the culture supernatant, and these particles contained viral genomic RNA,
      demonstrating that the E protein is essential for PRRSV infection but dispensable
      for virion assembly. Electron microscopy suggests that the P129-DeltaE virions
      assembled in the absence of E had a similar appearance to the wild-type
      particles. Strand-specific RT-PCR demonstrated that the E protein-negative, non
      infectious P129-DeltaE virus particles were able to enter cells but further steps
      of replication were interrupted. The entry of PRRSV has been suggested to be via
      receptor-mediated endocytosis, and lysomotropic basic compounds and known ion
      channel blocking agents both inhibited PRRSV replication effectively during the
      uncoating process. The expression of E protein in Escherichia coli-mediated cell
      growth arrests and increased the membrane permeability. Cross-linking experiments
      in cells infected with PRRSV or transfected with E gene showed that the E protein
      was able to form homo-oligomers. Taken together, our data suggest that the PRRSV
      E protein is likely an ion-channel protein embedded in the viral envelope and
      facilitates uncoating of virus and release of the genome in the cytoplasm.

PMID- 16904149
TI  - Primate cytomegalovirus US12 gene family: a distinct and diverse clade of seven
      transmembrane proteins.
AB  - Human cytomegalovirus (HCMV; Human herpesvirus 5) and the other betaherpesviruses
      encode a number of distinct gene families, including the US12 family, which is
      represented only in the cytomegaloviruses of higher primates, and is comprised of
      a set of 10 contiguous genes (US12 through US21), each encoding a seven
      transmembrane (7TM) protein. Nonessential for replication in cell culture but
      well-conserved among clinical isolates, little is known of possible US12 family
      member functions, other than a previously identified amino acid sequence
      similarity between US21 and a group of 7TM proteins that include known inhibitors
      of apoptosis, and a very limited description of similarity between US12 family
      members and G-protein-coupled receptors (GPCR). As a prelude to biochemical
      analysis, we have conducted a detailed analysis of the relationships among US12
      family members and between these proteins and other proteins, particularly GPCR
      and other 7TM molecules. In most cases, the closest relatives of individual genes
      are their colinear counterparts in the other viruses. Thus, the initial
      duplication and divergence events that resulted in the current version of the
      US12 family preceded divergence of the rhesus and hominoid lineages. Our
      phylogenetic analysis indicates that the US12 family represents a distinct branch
      of the 7TM superfamily. Although they are distantly related, at least some of the
      US12 family members may have GPCR-related properties, but they are also likely to
      embody functions and mechanisms that differ from more conventional GPCRs. Our
      analyses suggest that the 7TM structure of US12 family members constitutes a
      functionally flexible structural scaffold that can be readily adapted to diverse
      functional ends. This strategy may be the driving force in the emergence of the
      several families of duplicated and diverged betaherpesvirus genes.

PMID- 16904150
TI  - In vivo and in vitro analyses of a Bombyx mori nucleopolyhedrovirus mutant
      lacking functional vfgf.
AB  - All lepidopteran baculovirus genomes sequenced to date encode a viral fibroblast
      growth factor homolog (vfgf), suggesting that vfgf may play an important role in
      the infection cycle of lepidopteran baculoviruses. Here, we describe the
      characterization of a Bombyx mori nucleopolyhedrovirus (BmNPV) mutant lacking
      functional vfgf. We constructed a vfgf deletion mutant (BmFGFD) and characterized
      it in BmN cells and B. mori larvae. We observed that budded virus (BV) production
      was reduced in BmFGFD-infected BmN cells and B. mori larvae. The larval bioassays
      also revealed that deletion of vfgf did not reduce the infectivity; however, the
      mutant virus did take 20 h longer to kill B. mori larvae than wild-type BmNPV,
      when tested either by BV injection or by polyhedrin-inclusion body ingestion.
      These results suggest that BmNPV vfgf is involved in efficient virus production
      in BmN cells and B. mori larvae.

PMID- 16904151
TI  - Baboon model for West Nile virus infection and vaccine evaluation.
AB  - Animal models that closely mimic the human condition are of paramount
      significance to study pathogenic mechanisms, vaccine and therapy scenarios. This
      is particularly true for investigations that involve emerging infectious
      diseases. Nonhuman primate species represent an alternative to the more
      intensively investigated rodent animal models and in a number of instances have
      been shown to represent a more reliable predictor of the human response to
      infection. West Nile virus (WNV) has emerged as a new pathogen in the Americas.
      It has a 5% fatality rate, predominantly in the elderly and immune compromised.
      Typically, infections are cleared by neutralizing antibodies, which suggests that
      a vaccine would be efficacious. Previously, only macaques had been evaluated as a
      primate model for WNV vaccine design. The macaques did not develop WNV disease
      nor express the full complement of IgG subclasses that is found in humans. We
      therefore explored baboons, which exhibit the similar four IgG subclasses
      observed in humans as a new model for WNV infection and vaccine evaluation. In
      this present report, we describe the experimental infection of baboons with WNV
      and test the efficacy of an inactivated WNV vaccination strategy. All
      experimentally infected animals developed transient viremia and subsequent
      neutralizing antibodies. Anti-WNV IgM antibodies peaked at 20 days post
      infection. Anti-WNV IgG antibodies appeared later and persisted past 60 days.
      Prior vaccination with chemically inactivated virus induced neutralizing titers
      and a fast, high titer IgG recall response, which resulted in lower viremia upon
      challenge. This report is the first to describe the development of the baboon
      model for WNV experimental infection and the utility of this model to
      characterize the immunologic response against WNV and a candidate WNV vaccine.

PMID- 16904152
TI  - Characterization of human immunodeficiency virus type 1 (HIV-1) containing
      mutations in the nucleocapsid protein at a putative HIV-1 protease cleavage site.
AB  - The HIV-1 nucleocapsid protein (NC) has been hypothesized to be cleaved by the
      viral protease (PR) during early infection. Characterization of viruses, with
      amino-acid substitutions that modulate PR cleavage of NC in vitro, was performed
      in cell culture. Two of the NC mutants, NCN17F and NCN17G, had decreased
      infectivity and exhibited severe H9 replication defects. Examination of viral DNA
      after infections revealed defects in reverse transcription and integration,
      although integration defects were cell-type dependent. However, while the defects
      in reverse transcription and integration correlate with lowered infectivity in a
      single-round of infection, they did not approach the magnitude of the replication
      defect measured in H9 cells over multiple rounds. Importantly, we fail to see
      evidence that H9 cells are re-infected with the NCN17G and NCN17F viruses 24 h
      after the initial infection, which suggests that the principal defect caused by
      these NC mutations occurs during late events of viral replication.

PMID- 16904154
TI  - Virus-like particles derived from major capsid protein VP1 of different
      polyomaviruses differ in their ability to induce maturation in human dendritic
      cells.
AB  - As polyomavirus major capsid protein VP1-derived virus-like particles (VLPs) have
      been demonstrated to be highly immunogenic, we studied their interaction with
      human dendritic cells (hDCs). Exposure of hDCs to VLPs originating from murine
      (MPyV) or hamster polyomavirus (HaPyV) induced hDC maturation. In contrast,
      exposure of hDCs to VLPs derived from human polyomaviruses (BK and JC) and simian
      virus 40 (SV40) only marginally induced DC maturation. The hDCs stimulated by
      HaPyV- or MPyV-derived VLPs readily produced interleukin-12 and stimulated CD8
      positive T-cell responses in vitro. The highest frequencies of activated T cells
      were again observed after pulsing with HaPyV- and MPyV-derived VLPs. Monocyte
      derived hDCs both bound and internalized the various tested polyomavirus VP1
      derived VLPs with different levels of efficiency, partially explaining their
      individual maturation potentials. In conclusion, our data suggest a high
      variability in uptake of polyomavirus-derived VLPs and potency to induce hDC
      maturation.

PMID- 16904155
TI  - Characterization of the human chemerin receptor--ChemR23/CMKLR1--as co-receptor
      for human and simian immunodeficiency virus infection, and identification of
      virus-binding receptor domains.
AB  - Studies were conducted to elucidate co-receptor spectrum and function of the
      inflammatory receptor, CMKLR1/ChemR23, which was recently identified as the
      receptor for the cystatin-like chemoattractant, TIG2, also named chemerin. An
      infection model was applied based on stably transfected NP-2.CD4 host cells
      expressing various co-receptor constructs and exposed to panels of HIV-1, HIV-2
      and SIV primary isolates. In a panel of 27 HIV-1 isolates tested, 12 isolates
      could use CMKLR1/ChemR23. As expected from a relatively high sequence homology
      with the extracellular domains of CCR3, HIV-1 isolates showing R3 tropism were
      particularly efficient in using CMKLR1/ChemR23. In addition, 5 out of 7 HIV-2
      isolates and 13 out of 15 SIV (SMM-3 origin) used CMKLR1/ChemR23, in accordance
      with the previously documented ability of these isolates to use several co
      receptors. In order to define important extracellular epitopes for the viral
      interaction, a hybrid receptor model was applied. This was based on the fact that
      the rat receptor, although structurally very similar to the human orthologue, was
      inefficient as viral co-receptor. When the rat receptor was "humanized" to
      include regions unique to the human receptor (N-terminus or second extracellular
      loop), exposure to HIV-1, HIV-2 and SIV isolates resulted in infection. The
      relative importance of the two critical receptor regions differed between HIV
      1/HIV-2 on the one hand and SIV on the other. The results strongly support that
      the chemerin receptor, in the presence of CD4, functions as a "minor co-receptor"
      promoting infection by these classes of viruses.

PMID- 16904153
TI  - A DNA prime-oral Listeria boost vaccine in rhesus macaques induces a SIV-specific
      CD8 T cell mucosal response characterized by high levels of alpha4beta7 integrin
      and an effector memory phenotype.
AB  - In this study in Rhesus macaques, we tested whether IL-12 or IL-15 in a DNA prime
      oral Listeria boost amplifies the SIV-Gag-specific CD8 mucosal response. SIV
      specific CD8 T cells were demonstrated in the peripheral blood (PB) in all test
      vaccine groups, but not the control group. SIV-Gag-specific CD8 T cells in the PB
      expressed alpha4beta7 integrin, the gut-homing receptor; a minor subset co
      express alphaEbeta7 integrin. SIV-Gag-specific CD8 T cells were also detected in
      the gut tissue, intraepithelial (IEL) and lamina propria lymphocytes (LPL) of the
      duodenum and ileum. These cells were characterized by high levels of beta7
      integrin expression and a predominance of the effector memory phenotype. Neither
      Il-12 nor IL-15 amplified the frequency of SIV-specific CD8 T cells in the gut.
      Thus, the DNA prime-oral Listeria boost strategy induced a mucosal SIV-Gag
      specific CD8 T cell response characterized by expression of the alpha4beta7
      integrin gut-homing receptor.

PMID- 16904156
TI  - Poor recognition of HIV-1 Nef protein by CD8 T cells from HIV-1-infected
      children: impact of age.
AB  - Recognition of various HIV proteins by CD8 T cells from HIV-infected children was
      determined by two functional assays. First, using an Elispot assay, we show that
      80% of patients recognized Gag, 77% recognized Pol, 61% recognized Env, 44%
      recognized Nef and 29% recognized Vif. Frequencies of Gag-, Pol-, and Env
      specific IFN-gamma producing CD8 T cells were higher than frequencies of Nef and
      Vif-specific CD8 T cells. The poor recognition of Nef by ex vivo CD8 T cells was
      confirmed by CTL assays performed in HAART naive children: 25% of children had
      positive response against Nef versus 44, 63 and 62% for Env, Gag, and Pol,
      respectively. Memory Gag-specific CTL were positively correlated with age,
      whereas Nef-specific CTL were negatively correlated with age. The poor Nef
      specific CD8 T cell response in HIV-infected children contrasts with dominance of
      Nef-specific responses in infected adults.

PMID- 16904157
TI  - Geometrical basis of perception of gaze direction.
AB  - Perception of gaze direction depends not only on the position of the irises
      within the looker's eyes but also on the orientation of the looker's head. A
      simple analysis of the geometry of gaze direction predicts this dependence. This
      analysis is applied to explain the Wollaston effect, the Mona Lisa effect, and
      the newly presented Mirror gaze effect. In an experiment synthetic faces were
      used in which the position of the iris and the angle of head rotation were
      varied. Different groups of subjects judged iris position, head rotation, and
      gaze direction of the same stimuli. The results illustrate how cues of iris
      location and head orientation interact to determine perceived gaze direction.

PMID- 16904158
TI  - Bioremediation of zinc using Desulfotomaculum nigrificans: bioprecipitation and
      characterization studies.
AB  - Desulfotomaculum nigrificans, a typical sulfate reducing bacterium (SRB) was
      successfully grown in the presence of 12-210 mg/L of zinc. Complete bioremoval of
      zinc was achieved in 2 days for 12 mg/L while the bioremoval efficiency was about
      70% in 40 days in the presence of 210 mg/L initial concentration of zinc,
      attesting to the inhibition of bacterial cell growth at higher zinc
      concentrations. The bioremoval mechanism was predominantly governed by
      bioprecipitation with biosorption contributing to a minor extent. The amount of
      protein present in the extracellular secretions obtained by growth of SRB in
      modified Baars' medium devoid of iron was the highest followed by those obtained
      in the presence of zinc or iron, in that order. Bioremediation studies carried
      out using a specially designed set-up, facilitating the transfer of biogenically
      produced hydrogen sulfide gas to a separate precipitation assembly, confirmed
      that zinc could be successfully precipitated from its corresponding sulfate
      solution, varying in concentration from 10 to 20,000 mg/L. Detailed
      characterization of the various zinc sulfide precipitates by EDAX and X-ray
      diffraction analysis conformed to wurtzite structure. The isoelectric points of
      high purity zinc sulfide and that of chemically synthesized, biogenically
      produced and zinc sulfide precipitated using bacterially produced hydrogen
      sulfide gas (BPH-ZnS) were located at pH 3, 7.8, 2.8 and 8, respectively.

PMID- 16904159
TI  - Comments on Ouyang, Y., Evaluation of river water quality monitoring stations by
      principal component analysis. Water Research 39 (2005) 2621-2635.

PMID- 16904160
TI  - Seasonal changes of metal accumulation and distribution in shining pondweed
      (Potamogeton lucens).
AB  - In this study, submerged aquatic plant Potamogeton lucens, corresponding sediment
      and water samples were seasonally collected from Lake Sapanca (Turkey) and
      analysed for their heavy metal contents (Pb, Cr, Cu, Mn, Ni, Zn and Cd). While
      heavy metals concentrations in the water samples were decreased as
      Zn>Cr>Ni>Pb>Mn>Cu>Cd, in sediment samples were Mn>Zn>Ni>Cu>Cr>Pb>Cd,
      respectively. Generally, heavy metals concentrations in the plant tissues were
      decreased in sequence of Mn>Zn>Cu>Ni>Cr>Pb>Cd. It was determined that Cu, Mn and
      Zn were actively transported to the root, where they were accumulated especially
      in autumn. Lower accumulation factor ratios were seen in spring than other
      seasons. Cd exhibited a relatively clear pattern of increasing accumulation in P.
      lucens with increasing sediment metal concentrations. Significant positive
      correlations were observed between Cr, Cu, Ni and Cd contents in sediment and Cd
      contents in root of P. lucens. The investigations suggested that Ni and Mn have a
      tendency to be accumulated in leaf especially in autumn and Cr and Cd to be
      accumulated in shoot especially in summer.

PMID- 16904161
TI  - Gamma radiation-induced grafting of a cationic monomer onto chitosan as a
      flocculant.
AB  - Grafting of (2-methacryloyloxyethyl) trimethyl ammonium chloride onto chitosan
      through gamma-radiation in acidic aqueous solutions was achieved for production
      of a novel flocculant. The grafted copolymer was characterized by Fourier
      transform infrared, X-ray powder diffraction and thermogravimetric analysis. The
      effects of reaction parameters, such as total absorbed dose, dose rate, monomer
      concentration and temperature, on grafting percentage were investigated. The
      flocculation capacities of the grafted copolymer were evaluated with 0.25% (w/v)
      kaolin suspensions using the standard jar test. The results demonstrate the
      superiority of the grafted copolymer over chitosan as a flocculant.

PMID- 16904162
TI  - Speciation and quantification of vapor phases in soy biodiesel and waste cooking
      oil biodiesel.
AB  - This study characterizes the compositions of two biodiesel vapors, soy biodiesel
      and waste cooking oil biodiesel, to provide a comprehensive understanding of
      biodiesels. Vapor phases were sampled by purging oil vapors through thermal
      desorption tubes which were then analyzed by the thermal desorption/GC/MS system.
      The results show that the compounds of biodiesel vapors can be divided into four
      groups. They include methyl esters (the main biodiesel components), oxygenated
      chemicals, alkanes and alkenes, and aromatics. The first two chemical groups are
      only found in biodiesel vapors, not in the diesel vapor emissions. The
      percentages of mean concentrations for methyl esters, oxygenated chemicals,
      alkanes and alkenes, and aromatics are 66.1%, 22.8%, 4.8% and 6.4%, respectively
      for soy biodiesel, and 35.8%, 35.9%, 27.9% and 0.3%, respectively for waste
      cooking oil biodiesel at a temperature of 25+/-2 degrees C. These results show
      that biodiesels have fewer chemicals and lower concentrations in vapor phase than
      petroleum diesel, and the total emission rates are between one-sixteenth and one
      sixth of that of diesel emission, corresponding to fuel evaporative emissions of
      loading losses of between 106 microg l(-1) and 283 microg l(-1). Although diesels
      generate more vapor phase emissions, biodiesels still generate considerable
      amount of vapor emissions, particularly the emissions from methyl esters and
      oxygenated chemicals. These two chemical groups are more reactive than alkanes
      and aromatics. Therefore, speciation and quantification of biodiesel vapor phases
      are important.

PMID- 16904163
TI  - Meteorological parameters contributing to variability in 222Rn activity
      concentrations in soil gas at a site in Sapporo, Japan.
AB  - Continuous (222)Rn monitoring in soil gas since November 22, 2004 has revealed
      variability in activity concentration with time in the semi-natural woods on the
      campus of Hokkaido University in Sapporo, Japan. Among various factors affecting
      soil radon levels and variability, temperature was found to be dominant during
      three seasons when activity concentrations of (222)Rn showed a diurnal high and
      nocturnal low with a boundary around 10 o'clock in the morning. This pattern was
      disturbed by low pressure fronts with occasional rain. The activity gradually
      decreased as soil temperatures decreased from late November to mid-December.
      After the ground surface was completely covered with snow, soil radon levels
      became low with a small fluctuation. There were several peaks of (222)Rn on the
      time-series chart in winter. Those peaks appearing in early winter and early
      spring may be interpreted by considering meteorological parameters. In a few
      cases, the radon activity suddenly increased with increasing pressure in the soil
      at a depth of 10 cm, which may be associated with subsurface events such as
      seismic activity in the area.

PMID- 16904164
TI  - Mercury characterization in a soil sample collected nearby the DOE Oak Ridge
      Reservation utilizing sequential extraction and thermal desorption method.
AB  - A new attempt to characterize Hg speciation and to evaluate Hg mobility in soils
      was made by applying operationally defined speciation techniques coupled with
      fractionation of soil components to a soil sample collected just outside the Y-12
      boundary of the Oak Ridge Reservation (ORR) site. The soil sample was
      fractionated based on redoximorphic features and particle size and a sequential
      extraction procedure and thermal desorption technique were then applied to the
      fractionated soil components. The redoximorphic concentration component was
      observed to have higher Hg concentrations than the redoximorphic depletion
      component in the soil, and fine particles contained higher concentrations of Hg
      compared with coarse particles. The preliminary results of using thermal
      desorption as well as the sequential extraction procedure suggested that Hg0 and
      other "easily" vaporized Hg species accounted for 10-30% of total Hg in the soil.
      Sequential extraction analysis showed that both soluble and bioavailable Hg
      fractions were relatively small proportions whereas the organic matter bound
      mercury fraction constituted the major form of Hg species in the sample. The
      results suggest that Hg retained in the redoximorphic concentrations was less
      volatile and labile than Hg in the redoximorphic depletions possibly due to the
      strong binding affinity of Fe/Mn oxides and organic matter to Hg.

PMID- 16904165
TI  - Mapping of spatial multi-scale sources of arsenic variation in groundwater on
      ChiaNan floodplain of Taiwan.
AB  - This study applied multivariate factorial kriging to derive the characteristics
      of the spatial variations of groundwater arsenic distributions at different
      scales on the ChiaNan floodplain, Taiwan. Seven variables (dissolved oxygen,
      oxidation-reduction potential, alkalinity, sulfate, iron cations, manganese
      cations and total organic carbon) and Arsenic were adopted to analyze the
      mechanisms of arsenic enrichments in groundwater. The hydrogeological environment
      had spatial and quantitative influences on arsenic enrichments at different
      scales. The regional scale was set to 32 km referring to the extension distance
      of flow paths to reflect the effects of flushing in the aquifer, while the local
      scale was set to 16 km referring to the farthest distance of seawater intrusion
      to determine the influence of seawater intrusion. The results of factorial
      kriging suggested that arsenic releases resulted partially from pyrite oxidation
      during the flushing at the regional scale and partially due to the siderite
      dissolution at the local scale. Overall, the alkalinity dominated arsenic
      distribution in groundwater at both the regional and local scales. The
      multivariate factorial kriging results also demonstrated that seawater intrusion
      slightly affected the increase of arsenic in groundwater, accounting for only
      17.3% of total variation. However, the interaction of seawater intrusion and
      arsenic distribution in space indicated that seawater intrusion restrained the
      distribution of arsenic from the areas where seawater was located. High dissolved
      oxygen was found at where over-pumping induced drawdown cones occurred and also
      limited the spatial variation of arsenic. Our findings indicate that multivariate
      factorial kriging can be a useful mapping tool to improve understanding of the
      mechanism of arsenic release in groundwater at different scales. And the results
      conducted from the application of multivariate factorial kriging in southwestern
      Taiwan reveal the important influences of the hydrogeological processes, either
      artificial or natural, on the arsenic variations in groundwater.

PMID- 16904166
TI  - Intraperitoneal cisplatin therapy in ovarian cancer: comparison with standard
      intravenous carboplatin and paclitaxel.

PMID- 16904167
TI  - Screening for ovarian cancer by transvaginal ultrasound and serum CA125
      measurement in women with a familial predisposition: a prospective cohort study.
AB  - OBJECTIVE: This study evaluates the accuracy of transvaginal ultrasound (TVUS) in
      combination with CA125 to detect ovarian cancer in women at hereditary risk for
      ovarian cancer. METHODS: A semi-annual surveillance protocol comprising CA125
      measurement and TVUS was offered to 676 women including 85 BRCA mutation
      carriers. Surgical intervention was performed if TVUS revealed a suspicious cyst
      or if elevated CA125 levels or cystic lesions persisted in two consecutive
      examinations. RESULTS: Ten women underwent histological verification that
      revealed one serous cystadenocarcinoma stage Ic. No interval ovarian cancer
      occurred. The specificity of surgical intervention reached 98.7% (95% confidence
      interval (CI): 97.5% to 99.3%) and a positive predictive value (PPV) of 10% (95%
      CI: 1.8% to 40.4%). CONCLUSION: The low PPV is due to the unexpectedly low
      incidence of ovarian cancer. Large scale investigations including details on
      potential confounders and modifiers are needed to further evaluate accuracy and
      effectiveness of ovarian cancer screening for women at high risk.

PMID- 16904168
TI  - Primary extracranial meningioma of the pelvis: a light microscopic,
      immunohistochemical, and ultrastructural study.
AB  - BACKGROUND: Extracranial meningiomas are rare tumors which have been described in
      head and neck. The occurrence in mediastinum and retroperitoneum is even rarer.
      This presented case records a unique location, a meningioma arising in pelvis.
      CASE: A 52-year-old woman presented with an ovarian mass. The histology of the
      resected tumor revealed sheets of bland epithelioid cells arranged in prominent
      whorls with psammoma bodies typical of meningothelial meningioma.
      Immunohistochemical analysis demonstrated diffuse strong positivity for vimentin
      and epithelial membrane antigen (EMA). There was moderate reactivity for
      cytokeratin, estrogen (ER) and progesterone (PR) receptors. By electron
      microscopy, the tumor cells expressed desmosomes and abundant intermediate
      filaments. CONCLUSION: According to our review of literature, this is the first
      reported case of a primary pelvic meningioma. Its benign appearance and 4-year
      disease-free survival without clinical or radiological evidence of intracranial
      disease favors the pelvis as the primary site.

PMID- 16904170
TI  - Phase II study of neoadjuvant chemotherapy with mitomycin-c, vincristine and
      cisplatin (MVC) in patients with stages IB2-IIB cervical carcinoma.
AB  - OBJECTIVE: The efficacy and toxicity of neoadjuvant chemotherapy (NAC) with
      mitomycin-C, vincristine and cisplatin (MVC) were assessed in bulky cervical
      carcinoma patients. METHODS: Forty-six patients with stage IB2 to IIB cervical
      cancer were treated with intravenous combination of mitomycin-C 10 mg/m(2),
      vincristine 1 mg/m(2) and cisplatin 75 mg/m(2) every 3 weeks. After three cycles
      of NAC, the patients either underwent surgery or radiation therapy, depending on
      their suitability for radical hysterectomy. RESULTS: All 46 patients enrolled in
      this study were suitable for surgery after NAC. Twenty (44%) patients had risk
      factors after surgery and received postoperative radiation. Toxic nonhematologic
      reactions consisted primarily of grades 1-2 nausea and vomiting (87%) and the
      most common hematologic toxicity was anemia (60%). Clinical responses occurred in
      83% (38/46) of patients, including 24% (11/46) with a complete response (CR) and
      13% (6/46) with a pathologically determined complete response. For a median
      follow up period of 28 months, the 3-year disease-free and overall survival rates
      were 74% and 80%, respectively. Pathologically confirmed lymph node metastasis or
      parametrial involvement and an initial tumor size > or =4 cm were associated with
      shorter disease-free survival (P=0.040, P=0.000, P=0.025, respectively).
      CONCLUSION: Intravenous administration of MVC as a NAC seems to be well tolerated
      and beneficial in patients with stage IB2 to IIB cervical cancer.

PMID- 16904171
TI  - The role of insulin-like growth factor-I and growth factor-associated signal
      transduction pathways in estradiol and progesterone facilitation of female
      reproductive behaviors.
AB  - We are examining the role of insulin-like growth factor-I (IGF-I) and downstream
      signal transduction pathways associated with growth factors (e.g., mitogen
      activated protein kinase, MAPK) in estradiol and progesterone facilitation of
      female reproductive behavior in rats. Brain IGF-I receptor activity is required
      for the long-term, priming actions of estradiol on the female reproductive axis.
      Infusions of an IGF-I receptor antagonist during estradiol priming blocks
      induction of hypothalamic alpha(1B)-adrenergic receptors and luteinizing hormone
      surges, and attenuates lordosis behavior. Infusion of MAPK and
      phosphatidylinositol-3-kinase inhibitors inhibitors during estradiol priming
      completely blocks hormone-facilitated lordosis. Because progestin receptors (PRs)
      can be phosphorylated and activated by MAPKs, growth factor signaling pathways
      may also participate in progesterone facilitation of reproductive behaviors.
      Infusion of a MAPK inhibitor in estradiol-primed rats blocks progestin
      facilitation and sequential inhibition of lordosis and proceptive behaviors.
      Interference with MAPK signaling also inhibits behavioral responses to cGMP and a
      delta-opioid agonist, both of which can activate MAPK in some cells. Thus MAPK is
      involved in the facilitation of lordosis and proceptive behaviors, perhaps by
      phosphorylation of hypothalamic PRs.

PMID- 16904172
TI  - Pindolol does not augment central serotonin function increases to citalopram in
      humans: an auditory evoked potential investigation.
AB  - Animal studies have demonstrated that the co-administration of pindolol and
      selective serotonin reuptake inhibitors (SSRIs) potentiate serotonergic
      functioning to a greater degree than SSRIs alone. However, clinical trials of
      pindolol augmentation in patients with major depressive disorder have reported
      contradictory findings, and the central effects of this treatment regime on
      serotonin functioning in humans are unknown. The current double-blind placebo
      controlled repeated measures investigation used the loudness dependence auditory
      evoked potential (LDAEP) to assess central serotonin functioning in healthy
      participants across three acute treatment conditions: placebo, citalopram (20
      mg), and pindolol (10 mg)+citalopram (20 mg). The current paper focuses on the
      effects of pindolol augmentation of citalopram as compared to the administration
      of citalopram alone. Enhancement of serotonin function with citalopram in
      comparison to placebo decreased the slope of the LDAEP (i.e. weaker LDAEP).
      However, there were no significant differences between the changes in the LDAEP
      induced by co-administration of pindolol and citalopram compared to citalopram.
      The present results indicate that, in healthy controls, pindolol augmentation of
      SSRIs does not potentiate central serotonin function to a greater degree than the
      administration of an SSRI alone. The findings may provide further support for why
      pindolol may not be an effective therapeutic strategy to augment serotonin
      function and antidepressant response.

PMID- 16904173
TI  - Chronic exercise decreases sensitivity to mu opioids in female rats: correlation
      with exercise output.
AB  - Aerobic exercise stimulates the release of endogenous opioid peptides and
      increases nociceptive (i.e., pain) threshold in a naloxone-reversible manner.
      During chronic exercise, sensitivity to the antinociceptive effects of morphine
      and other mu opioids decreases, leading some investigators to propose that
      exercise may lead to the development of cross-tolerance to exogenously
      administered opioid agonists. The purpose of the present study was to examine the
      effects of chronic exercise on sensitivity to mu opioids, and to determine if
      changes in opioid sensitivity during chronic exercise are correlated with
      exercise output. Eight female rats were obtained at weaning and housed in
      standard laboratory cages that did not permit any exercise beyond normal cage
      ambulation. Following 6 weeks under these conditions, opioids possessing a range
      of relative efficacies at the mu receptor (morphine, levorphanol, buprenorphine,
      butorphanol) were examined in a warm-water, tail-withdrawal procedure. Under
      sedentary conditions, all opioids produced dose-dependent increases in tail
      withdrawal latencies, and high levels of antinociception were observed for all
      drugs. Following these tests, rats were reassigned to exercise conditions and
      transferred to cages equipped with running wheels. Under these conditions, rats
      ran an average of 7154 rev/day (7869 m/day), with a range across rats from 4501
      to 10,164 rev/day (4951-11,180 m/day). Sensitivity to all four opioids decreased
      significantly during the exercise period, resulting in 2- to 5-fold decreases in
      the potency of morphine, levorphanol and buprenorphine, and decreases in the
      effectiveness of buprenorphine and butorphanol. When rats were returned to
      sedentary conditions, sensitivity to all four opioids increased significantly and
      returned to that observed prior to the exercise period. For all drugs, there was
      a positive correlation between exercise output and changes in opioid sensitivity
      between sedentary and exercise conditions. These data suggest that chronic
      exercise decreases sensitivity to mu opioids in female rats, and that these
      changes in sensitivity are positively correlated with exercise output.

PMID- 16904174
TI  - Induction of pluripotent stem cells from mouse embryonic and adult fibroblast
      cultures by defined factors.
AB  - Differentiated cells can be reprogrammed to an embryonic-like state by transfer
      of nuclear contents into oocytes or by fusion with embryonic stem (ES) cells.
      Little is known about factors that induce this reprogramming. Here, we
      demonstrate induction of pluripotent stem cells from mouse embryonic or adult
      fibroblasts by introducing four factors, Oct3/4, Sox2, c-Myc, and Klf4, under ES
      cell culture conditions. Unexpectedly, Nanog was dispensable. These cells, which
      we designated iPS (induced pluripotent stem) cells, exhibit the morphology and
      growth properties of ES cells and express ES cell marker genes. Subcutaneous
      transplantation of iPS cells into nude mice resulted in tumors containing a
      variety of tissues from all three germ layers. Following injection into
      blastocysts, iPS cells contributed to mouse embryonic development. These data
      demonstrate that pluripotent stem cells can be directly generated from fibroblast
      cultures by the addition of only a few defined factors.

PMID- 16904175
TI  - Effect of simulated pulpal pressure on dentin permeability and adhesion of self
      etch adhesives.
AB  - OBJECTIVES: Dentin bonds made with one-bottle etch-and-rinse and self-etch
      adhesives are affected by the formation of interfacial blisters, porosities and
      deterioration. The first objective of this study was to evaluate the fluid flow
      through resin-dentin interfaces created by self-etching adhesives applied to deep
      dentin using a replica technique and by directly measuring dentin permeability
      (P). The second objective was to examine the effect of intrapulpal pressure on
      the microtensile bond strength of these adhesives. METHODS: A fluid-transport
      model was used to measure the fluid permeability (%P) through different
      adhesives. Impressions of bonded dentin were taken with a polyvinylsiloxane
      impression material to monitor fluid transudation from the surface of the
      adhesive. Positive replicas were fabricated for SEM examination. Two groups of
      resin-bonded specimens (pulpal pressure versus no pulpal pressure) were created
      for microtensile bond strength evaluation. Adhesive application was performed
      under 0 cm H(2)O. Pulpal pressure group was submitted to 20 cm H(2)O of pulpal
      pressure during build-up procedures. RESULTS: Clearfil Protect Bond exhibited the
      lowest permeability and fewest numbers of fluid droplets over the surface of the
      bonded dentin. G-Bond and Clearfil-S3 Bond were more permeable than Clearfil
      Protect Bond. One Up Bond F was the most permeable adhesive. A highly significant
      correlation was observed between the relative permeability of these adhesives
      (%P) and the number of fluid droplets on the adhesive surfaces. The application
      of pulpal pressure significantly reduced bond strength. SIGNIFICANCE: Resin
      dentin bonds created by contemporary self-etch adhesives are susceptible to fluid
      permeation induced by pulpal pressure. HEMA-based adhesives showed the largest
      reductions in bond strengths after pulpal pressure application.

PMID- 16904176
TI  - Evaluation of the sliding distance in shortening muscles and in polymerizing
      actin from Hill's force-velocity equation.
AB  - The relationship derived earlier between the sliding distance, Deltal(m), and
      a/P(0), the characteristic parameter of Hill's force-velocity equation for muscle
      contraction, was re-formulated in order to get a more general relationship which
      can be applied also to other biological mechano-chemical energy converters: alpha
      x Deltal(m)=phi (0)(a/P(0))Deltal(m)=-Deltag where Deltag is the free energy
      change accompanying the hydrolysis of one ATP molecule while alpha and phi (0)
      are, respectively, the average forces developed by a myosin head-actin complex
      which are responsible for shortening and for isometric tension generation. These
      two molecular forces are different in magnitude and in nature and it is
      demonstrated that alpha , not phi (0), is the true contractile force. The values
      of alpha and of phi (0) have been calculated for three muscles. The equation has
      been successfully applied to actin polymerization-based motility. The value of
      Deltag in different muscles under different environmental conditions can be
      easily determined from this equation with the value of Deltal(m) derived
      experimentally.

PMID- 16904177
TI  - 3D hepatocyte monolayer on hybrid RGD/galactose substratum.
AB  - Hepatocyte-based applications such as xenobiotics metabolism and toxicity studies
      usually require hepatocytes anchoring onto flat substrata that support their
      functional maintenance. Conventional cell culture plates coated with natural
      matrices or synthetic ligands allow hepatocytes to adhere tightly as two
      dimensional (2D) monolayer but these tightly anchored hepatocytes rapidly lose
      their differentiated functions. On galactosylated substrata, hepatocytes adhere
      loosely; and readily form three-dimensional (3D) spheroids that can maintain high
      levels of cellular functions. These spheroids detach easily from the substrata
      and exhibit poor mass transport properties unsuitable for many applications.
      Here, we have developed a hybrid RGD/galactose substratum based on polyethylene
      terephthalate film conjugated with both RGD peptide and galactose ligand to
      enhance cell adhesion and functions synergistically. Primary hepatocytes adhere
      effectively onto the transparent hybrid substratum in 96-well plates as monolayer
      while exhibiting high levels of liver-specific functions, morphology and cell
      cell interactions typically seen in the 3D hepatocyte spheroids. The hepatocytes
      cultured onto the hybrid substratum also exhibit high levels of sensitivity to a
      model drug acetaminophen similar to the 3D hepatocyte spheroids. The monolayer of
      hepatocytes exhibiting the 3D cell behaviors on this flat hybrid substratum can
      be useful for various applications requiring both effective mass transfer and
      cellular support.

PMID- 16904178
TI  - Effects of the neuropeptides substance P, calcitonin gene-related peptide,
      vasoactive intestinal polypeptide and galanin on the production of nerve growth
      factor and inflammatory cytokines in cultured human keratinocytes.
AB  - Neuropeptides released from the cutaneous sensory nerve endings have
      neurotransmitter and immunoregulatory roles; they exert mitogenic actions and can
      influence the functions of different cell types in the skin. The aims of this
      study were a systematic investigation of the effects of the neuropeptides
      substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal
      polypeptide (VIP) and galanin (GAL) on the inflammatory cytokine production (IL
      1alpha, IL-8 and TNF-alpha) of the keratinocytes, and a study of their role in
      the production and secretion of nerve growth factor (NGF) and its precursor
      molecule (proNGF). Cultures of normal human keratinocytes were treated with 10(
      8)M SP, CGRP, VIP or GAL for 30 min. After different time intervals, cells were
      harvested for total RNA isolation; in addition, cell lysates and supernatants
      were collected. The effects of the neuropeptides on the mRNA expressions of the
      different cytokines and NGF were investigated by Q-RT-PCR and the protein levels
      were studied by means of ELISA assays and Western blotting. Each of the four
      neuropeptides induced increases in the expressions of IL-1alpha, IL-8 and TNF
      alpha mRNA. Increases appeared in the amount of the IL-1alpha protein in the
      supernatants of neuropeptide-treated cells, and the IL-8 secretion was mildly
      elevated, while secretion of TNF-alpha remained undetectable. The four
      neuropeptides increased the NGF mRNA expression to different extents. In the cell
      lysates of the keratinocytes, only proNGF could be detected, its concentration in
      the neuropeptide-treated cells being approximately twice that in the time-matched
      controls. Both control cultures and neuropeptide-treated cultures were found to
      secrete proNGF and mature NGF, but neuropeptide-treated cell cultures produced
      markedly higher (3-7-fold) amounts of NGF-like immunoreactive materials. The
      results demonstrated that neuropeptides released from cutaneous nerves after an
      injurious stimulus are able to induce an upregulation of IL-1alpha and IL-8
      production; they are additionally able to influence the expressions of proNGF/NGF
      and their secretion from the keratinocytes. These findings may contribute toward
      an understanding of the neural influence on skin health and disease.

PMID- 16904179
TI  - Effect of PACAP in 6-OHDA-induced injury of the substantia nigra in intact young
      and ovariectomized female rats.
AB  - Pituitary adenylate cyclase activating polypeptide (PACAP) has neuroprotective
      effects in various neuronal cultures and in models of brain pathologies in vivo.
      Among others, it protects dopaminergic neurons in vitro, against 6-OHDA- and
      rotenone-induced injury. Recently, we have shown that PACAP reduces dopaminergic
      cell loss and ameliorates behavioral outcome following unilateral 6-OHDA-induced
      injury of the substantia nigra in male rats. However, after castration, PACAP led
      only to a slight amelioration of the behavioral symptoms. The aim of the present
      study was to investigate the degree of neuroprotection exerted by PACAP in female
      rats, using the same model. It was found that PACAP had no effect on the
      dopaminergic cell loss in intact female rats, only caused amelioration of certain
      acute behavioral signs. In contrast, PACAP effectively increased dopaminergic
      cell survival and decreased behavioral deficits in ovariectomized females. These
      results indicate that the neuroprotective effect of PACAP in a rat model of
      Parkinson's disease is gender-specific.

PMID- 16904180
TI  - Cortical EEG correlates of successful memory encoding: implications for lifespan
      comparisons.
AB  - In the course of their lives, individuals experience a myriad of events. Some of
      them leave stable traces, and others fade away quickly. Recent advances in
      functional imaging methods allow researchers to contrast neuronal patterns of
      remembered against not remembered events at initial encoding. Research on young
      adults using functional magnetic resonance imaging (fMRI), intracranial, and
      standard electroencephalographic (EEG) recordings has identified differences
      between remembered and not remembered items in patterns of medio-temporal and
      prefrontal brain activity. However, little is known about the ways in which such
      neuronal patterns of successful encoding evolve across the lifespan as a function
      of maturation, senescence, and the accumulation of experience. Here, we first
      review empirical evidence on neuronal correlates of successful memory from middle
      childhood to old age. Based on the observation that associative and strategic
      components of episodic memory seem to follow different age gradients, we propose
      a conceptual framework for predicting age changes in neuronal patterns of
      successful encoding.

PMID- 16904181
TI  - SWIFT explorations of age differences in eye movements during reading.
AB  - Research on eye movements in reading has made significant advances during the
      past few years, due to both experimental and computational research. Age effects
      have not been extensively studied, but the overall pattern suggests more
      quantitative than qualitative differences in fixation durations and fixation
      probabilities. Here we focus on age-differential effects of word frequency on
      reading time and on probabilities of skipping a word or regressing to previous
      ones. We present an overview of SWIFT [Engbert, R., Nuthmann, A., Richter, E.M.,
      Kliegl, R., 2005. SWIFT: a dynamical model of saccade generation during reading.
      Psychological Review 112, 777-813], a fully implemented computational model of
      saccade generation and lexical processing during reading, based on spatially
      distributed processing over several words. Preliminary simulations of age
      differences recovered most, but not all experimental effects. Age differences in
      parameter estimates point towards an important role of visual acuity for
      oculomotor as well as lexical processing.

PMID- 16904182
TI  - The neuronal basis and ontogeny of empathy and mind reading: review of literature
      and implications for future research.
AB  - Social neuro-science has recently started to investigate the neuronal mechanisms
      underlying our ability to understand the mental and emotional states of others.
      In this review, imaging research conducted on theory of mind (ToM or mentalizing)
      and empathy is selectively reviewed. It is proposed that even though these
      abilities are often used as synonyms in the literature these capacities represent
      different abilities that rely on different neuronal circuitry. ToM refers to our
      ability to understand mental states such as intentions, goals and beliefs, and
      relies on structures of the temporal lobe and the pre-frontal cortex. In
      contrast, empathy refers to our ability to share the feelings (emotions and
      sensations) of others and relies on sensorimotor cortices as well as limbic and
      para-limbic structures. It is further argued that the concept of empathy as used
      in lay terms refers to a multi-level construct extending from simple forms of
      emotion contagion to complex forms of cognitive perspective taking. Future
      research should investigate the relative contribution of empathizing and
      mentalizing abilities in the understanding of other people's states. Finally, it
      is suggested that the abilities to understand other people's thoughts and to
      share their affects display different ontogenetic trajectories reflecting the
      different developmental paths of their underlying neural structures. In
      particular, empathy develops much earlier than mentalizing abilities, because the
      former relys on limbic structures which develop early in ontogeny, whereas the
      latter rely on lateral temporal lobe and pre-frontal structures which are among
      the last to fully mature.

PMID- 16904183
TI  - Fate of Irgarol 1051, diuron and their main metabolites in two UK marine systems
      after restrictions in antifouling paints.
AB  - Two major antifouling biocides used worldwide, Irgarol 1051 and diuron, and their
      degradation products in Shoreham Harbour and Brighton Marina, UK were studied
      during 2003-2004. The highest concentrations of Irgarol 1051 were 136 and 102 ng
      L(-1) in water and 40 and 49 ng g(-1) dry weight in sediments for Shoreham
      Harbour and Brighton Marina, respectively. As the degradation product of Irgarol
      1051, M1 was also widespread, with the highest concentration of 59 ng L(-1) in
      water and 23 ng g(-1) in sediments in Shoreham Harbour, and 37 ng L(-1) in water
      and 5.6 ng g(-1) in sediments in Brighton Marina. The target compounds showed
      enhanced concentrations during the boating season (May-July), when boats were
      being re-painted (January-February), and where the density of pleasure crafts was
      high. Overall, the concentration of Irgarol 1051 decreased significantly from
      late 2000 to early 2004, indicating the effectiveness of controlling its
      concentrations in the marine environment following restricted use. Diuron was
      only detected in 14% of water samples, and mostly absent from sediment samples.

PMID- 16904184
TI  - Synthesis, structure and biological activity of copper(II) complexes with
      oxolinic acid.
AB  - The neutral mononuclear copper complexes with the quinolone antibacterial drug
      oxolinic acid in the presence or not of a nitrogen donor heterocyclic ligand 1,10
      phenanthroline, 2,2'-bipyridine or 2,2'-dipyridylamine have been synthesized and
      characterized with infrared, UV-visible and electron paramagnetic resonance
      spectroscopies. The experimental data suggest that oxolinic acid acts as a
      deprotonated bidentate ligand and is coordinated to the metal ion through the
      pyridone and one carboxylate oxygen atoms. The crystal structure of (chloro)(1,10
      phenanthroline)(oxolinato) copper(II), 2, has been determined with X-ray
      crystallography. For all complexes a distorted square pyramidal environment
      around Cu(II) is suggested. The EPR (electron paramagnetic resonance) behavior of
      2 in aqueous solutions indicates mixture of dimeric and monomeric species. The
      investigation of the interaction of the complexes with calf-thymus DNA has been
      performed with diverse spectroscopic techniques and showed that the complexes are
      bound to calf-thymus DNA. The antimicrobial activity of the complexes has been
      tested on three different microorganisms. The complexes show a decreased
      biological activity in comparison to the free oxolinic acid.

PMID- 16904185
TI  - Metal ion-directed cooperative DNA binding of small molecules.
AB  - Compound (1), which consists of an oxine and a pyridinium group, was synthesized
      as a metal-responsive DNA binding ligand. Two 1s coordinate to a Cu(II) to form a
      stable dimer (1(2)-Cu), even in the presence of DNA. The binding of 1 with
      sonicated calf thymus DNA was enhanced by ca. 10(3) times after forming the
      dimer; the binding constants were estimated to be 3.2 x 10(4)M(-1) and 2.4 x
      10(7)M(-1) in the absence and the presence, respectively, of a half mole of
      Cu(II). The enormous acceleration of the binding is partly attributed to the
      generation of a dicationic charge by the formation of the dimer. High
      cooperativity between dimers could be also responsible; dimers would gather along
      the duplex as a template to form 1D spiral aggregates.

PMID- 16904186
TI  - Reductive nitrosylation of water-soluble iron porphyrins by S-nitroso-N
      acetylpenicillamine: rate constants and EPR characterization.
AB  - Reductive nitrosylation of the water-soluble iron derivatives of the cationic
      Fe(III)(TMPyP) and anionic Fe(III)(TPPS) porphyrins [where TMPyP=tetra-meso-(4-N
      methylpyridiniumyl)porphinate and TPPS=tetra-meso-(4-sulfonatophenyl)porphinate]
      by the nitric oxide donor S-nitroso-N-acetylpenicillamine (SNAP) was studied
      using optical absorption spectroscopy and electron paramagnetic resonance.
      Nitrosylation rates were obtained, the reaction was found to be first order in
      the SNAP concentration and the stoichiometry of the reaction was one to one. The
      similarity between the obtained second-order rate constants for both porphyrins,
      k(TMPyP)=0.84 x 10(3)M(-1)s(-1) and k(TPPS)=0.97 x 10(3)M(-1)s(-1), suggested
      that the reaction mechanism is approximately independent of the nature of the
      porphyrin meso-substituents. A mechanism was proposed involving the hydrolysis of
      SNAP by an out of plane liganded H(2)O yielding the sulfenic acid of N
      acetylpenicillamine and the transfer of NO(-) to Fe(III). The EPR (electron
      paramagnetic resonance) spectra of the SNAP- and gaseous NO-treated porphyrins
      were obtained and compared. The difference between the spectra of the cationic
      and anionic porphyrins indicates different local symmetry and Fe-N-O bond angle.
      SNAP-treatment produced much more resolved hyperfine structures than gaseous NO
      treatment.

PMID- 16904187
TI  - Dose-response relationship between number of comorbid anxiety disorders in
      adolescent bipolar/unipolar disorders, and psychosis, suicidality, substance
      abuse and familiality.
AB  - OBJECTIVES: To ascertain rates of panic, obsessive-compulsive (OCD) and social
      phobic disorders among adolescents with bipolar disorder (BP), unipolar major
      depressive disorder (MDD) and psychiatric comparison patients, to assess their
      relationships to suicidality, psychosis, comorbidity patterns and familiality.
      METHODS: The first author (SCD) interviewed 313 Latino adolescents using a
      structured interview based on the SCID. Family history was ascertained by live
      interview or interview by proxy. Patients were classified as BP, MDD, or non
      affectively ill comparison controls (CC). Data regarding suicidality and
      psychosis were collected. Regression analysis was used to test associations and
      control for confounding effects. Positive likelihood ratios were used to measure
      the dose-response relationships between number of anxiety disorders and measures
      of severity of illness and familial loading for affective illness. RESULTS: Of
      the total sample, 36.7% were BP, 44.7% MDD and 18.5% CC. In BP vs. MDD the odds
      of panic disorder were 4.4, of OCD 5.1, and of social phobia 3.3. MDD, in turn,
      were more likely to have these disorders than CC. BP (but not MDD) with panic
      disorder and social phobia, were more likely to have suicidal ideation; among the
      anxiety disorders, only social phobia was associated with having greater odds of
      suicide attempts. Among BP and MDD, patients with all three anxiety disorders
      were more likely to be psychotic. Presence of any mood disorder among first
      degree relatives substantially increased the odds of having panic disorder and
      social phobia. The presence of one comorbid anxiety disorder increased the odds
      of having another. Finally, there were dose-response relationships between number
      of anxiety disorders and measures of severity of illness and familial loading for
      affective illness. LIMITATIONS: Single interviewer using the SCID; cross
      sectional exploratory study. CONCLUSIONS: BP adolescents have a greater anxiety
      disorder burden than their MDD counterparts. The results are compatible with the
      hypothesis that heavy familial-genetic loading for affective illness in juveniles
      is associated with bipolarity, cumulative anxiety disorder comorbidity,
      suicidality and psychosis. These observations are in line with pioneering
      psychopathologic observation in the early 1900s by two French psychiatrists,
      Gilbert Ballet and Pierre Kahn, who saw common ground between what until then had
      been considered the distinct categories of the neuroses and cyclothymic
      (circular) psychoses. This perspective has much in common with current complex
      genetic models of anxious diatheses in bipolar disorder.

PMID- 16904188
TI  - Actigraphic predictors of the depressive state in students with no psychiatric
      disorders.
AB  - BACKGROUND: Insomnia is one of the characteristics of the early depressive state.
      One-third of university students has a mild depressive state. In this study, we
      examined whether the depressive state would be correlated with the actigraphic
      derived daytime activity levels (DAL) and total sleep time (TST) in students with
      no psychiatric disorders. METHOD: Consenting volunteers were monitored at home
      for 3-4 days with a wrist actigraph. The DALs for 3 h before noon (DAL-M) and
      after 13:00 h (DAL-A) were calculated. The states of sleep and wakefulness were
      judged based on the activity levels, using a special algorithm. On the first day
      of the recording, the subjects were requested to fill a questionnaire, "Center of
      Epidemiologic Scale for Depression Scale (CES-D)," to evaluate the severity of
      their depressive state. RESULTS: There was a significant correlation between the
      DAL-M and DAL-A in both males (r=0.52, n=27) and females (r=0.50, n=21). TST was
      significantly correlated with depressive state only in the females (r=-0.49,
      n=28). In contrast, there was no significant correlation between the DAL and the
      severity of the depressive state. By multiple regression analysis, TST was only a
      good predictor of depressive state. CONCLUSION: The results of this investigation
      suggest that TST could be used as an index of the depressive state. The TST
      values in this study decreased as the severity of the depressive state increased,
      which suggests an association between the severity of the depressive state and
      insufficient sleep.

PMID- 16904189
TI  - Diagnostic validity of assessment scales for depression in patients with
      schizophrenia.
AB  - The aim of this study was to examine the diagnostic validity of four commonly
      used assessment scales for depression in schizophrenia. The study population
      consisted of 84 inpatients meeting the DSM-IV criteria for schizophrenia.
      Depression in the study subjects was defined by the DSM-IV criteria for major
      depressive episode. The Positive and Negative Syndrome Scale (PANSS) and the
      Simpson-Angus Rating Scale (SARS) were used to differentiate depression from the
      negative and extrapyramidal symptom-related depressive phenomena in
      schizophrenia. The following four depression scales were assessed for their
      diagnostic validity as measures of depressive disorder in schizophrenia: the
      Calgary Depression Scale for Schizophrenia (CDSS), the Beck Depression Inventory
      (BDI), the Hamilton Rating Scale for Depression (HAM-D), and the depression
      subscale of the PANSS (PANSS-D). Of 84 patients with schizophrenia, 32 were
      diagnosed as having comorbid depressive disorder. The areas under the Receiver
      Operating Characteristic (ROC) curves of the CDSS, HAM-D, PANSS-D, and BDI were
      0.94, 0.89, 0.90, and 0.81, respectively. The area under the ROC curve of the
      CDSS was significantly greater than that of the BDI and tended to be more
      favorable than those for the HAM-D and the PANSS-D. Our study suggests that the
      CDSS may provide the best assessment for depression in patients with
      schizophrenia.

PMID- 16904190
TI  - A neuropsychological investigation into 'Theory of Mind' and enhanced risk of
      schizophrenia.
AB  - Theory of Mind (ToM) is the ability to correctly determine the intentions and
      behaviours of others. It is known that this capability is compromised in
      individuals with schizophrenia. It is has not been fully elucidated whether this
      observed phenomenon is of a state or trait nature. This study investigated
      whether ToM impairments could be linked to schizophrenia liability. A battery of
      ToM tests (the Hinting Task, a Self-Monitoring drawing task and cartoon picture
      stories) were used to compare healthy controls (n=13) with relatives of
      individuals with schizophrenia who had experienced psychotic symptoms (HR+, n=12)
      and those relatives who had not (HR-, n=13). All participants belonged to the
      Edinburgh High Risk Study. Significant group differences were seen on the Self
      Monitoring and cartoon tasks for the HR+ group, particularly those who had
      experienced symptoms at or around the time of testing. The observed ToM deficits
      measured by this battery of ToM tasks appeared to be related to state effects
      rather than enhanced risk of schizophrenia.

PMID- 16904191
TI  - Amphetamine triggers an increase in met-enkephalin simultaneously in brain areas
      and immune cells.
AB  - We analyzed effects of amphetamine on proenkephalin-derived peptides in brain
      areas and immune cells in rats. Acute, as well as a repeated amphetamine
      treatment, decreased the concanavalin-A-induced lymphocyte proliferation,
      concomitantly with an increase of free met-enkephalin in nucleus accumbens,
      prefrontal cortex, spleen, thymus and splenic macrophages. Proenkephalin protein
      increased in prefrontal cortex, thymus (32 kDa isoform), nucleus accumbens and
      spleen (44 kDa isoform), while proenkephalin mRNA levels decreased in brain stem.
      The influence of met-ENK in key brain areas for sensitization and in immune
      organs is consistent with the idea that changes on met-ENK could underlie
      amphetamine's effects on brain and IS.

PMID- 16904192
TI  - Suppression of autoimmune encephalomyelitis by a neurokinin-1 receptor antagonist
      -a putative role for substance P in CNS inflammation.
AB  - Substance P (SP) is an excitatory neurotransmitter in the central and peripheral
      nervous system. Most of its physiological functions are mediated through binding
      to the neurokinin-1 receptor (NK-1R). Recently, proinflammatory properties of SP
      have been described. In this study we utilized T cell transfer experimental
      autoimmune encephalomyelitis (EAE) to investigate the role of SP in CNS
      autoimmune disease. Treatment with the NK-1R antagonist CP-96,345 dramatically
      reduced clinical and histological signs of EAE if administered before disease
      onset. The protective effect of CP96,345 treatment was related to a reduced
      expression of the adhesion molecules ICAM-1 and VCAM-1 on CNS endothelia. The
      cellular composition or activation status of splenocytes was not affected by CP
      96,345 administration, while the secretion of proinflammatory Th1 cytokines was
      reduced in treated animals. Th2 cytokines remained largely unaffected by NK-1
      receptor antagonist treatment. In summary, our findings suggest that the
      protective effect of CP96,345 treatment is mediated by stabilization of the blood
      brain barrier and suppression of Th1 immunity.

PMID- 16904193
TI  - Critical role of preproenkephalin in experimental autoimmune encephalomyelitis.
AB  - Experimental autoimmune encephalomyelitis (EAE) is an organ-specific autoimmune
      disease model used to investigate mechanisms involved in the activation of self
      reactive T cells. Preproenkephalin (PPNK) is the gene that encodes the protein
      proenkephalin A that has been detected in the brain, adrenal cells and cells of
      the immune system. In this paper, whether PPNK plays a role in the development of
      EAE was investigated. PPNK-deficient and wild-type mice were immunized with the
      MOG(35-55) peptide and the development of EAE observed. Our results show that
      PPNK-deficient mice developed less severe clinical signs of disease than wild
      type mice, and with lower incidence. MOG(35-55)-specific T cells from PPNK
      deficient and wild-type mice produced IFNgamma and TNFalpha but no IL-4 or IL-10,
      indicative of a Th1 phenotype. However, the numbers of MOG(35-55)-specific
      IFNgamma-producing cells from immunized PPNK-deficient mice were largely reduced
      at early stages of disease. Interestingly, there was no difference in clinical
      signs or infiltrating mononuclear cells in the CNS between wild-type and PPNK
      deficient mice at the later stage of disease. Our results suggest that PPNK
      accelerates the generation of autoimmune IFNgamma-producing T cells and MOG(35
      55)-induced EAE.

PMID- 16904194
TI  - Effects of chimeric somatostatin-dopamine molecules on human peripheral blood
      lymphocytes activation.
AB  - BIM 23A761, selective for somatostatin receptors subtypes 2, 5 and the dopamine
      receptor subtype 2, and BIM 23A757 with affinity for SSTR2 and DAR2 were studied
      on human PBL proliferation and activation. BIM 23A761 was significantly more
      potent than specific SSTR and DAR2 agonists in suppressing lymphocyte
      proliferation induced by mitogen or alloantigen, while BIM 23A757 was more potent
      than specific SSTR2 and DAR2 agonists in suppressing antigen induced
      proliferation only. Both molecules displayed enhanced potency in suppressing
      IFNgamma and IL-6 secretion compared with the SSTR and DAR2 analogs, while only
      BIM 23A761 was able to inhibit IL-2 secretion and its effect is more potent than
      the control analogs. Furthermore BIM 23A761 inhibit cell progression into the S
      phase and then into the G2/M, while BIM 23A757 inhibited bromodeoxyuridine
      incorporation only during the S phase. Both chimeric molecules resulted
      significantly more effective than the respective controls.

PMID- 16904195
TI  - Distribution and prevalence of leukocyte phenotypes in brains of lupus-prone
      mice.
AB  - Autoantibody-mediated compromise of central neurotransmission is a pathogenic
      mechanism proposed in etiology of neuropsychiatric lupus (NP-SLE). Recent
      experimental data support the hypothesis that intrathecally-synthesized
      antibodies play a key role in brain damage and behavioral dysfunction. However,
      autoantibody-producing plasma cells have not yet been detected in brain tissue.
      We presently use contemporary immunohistochemical markers and flow cytometry to
      assess distribution and prevalence of plasma cells and other phenotypes, which
      infiltrate brains of lupus-prone MRL-lpr mice. The functional status of
      infiltrates was confirmed by in situ hybridization for TNF-alpha mRNA. Consistent
      with the notion of breached blood-CSF and blood-brain barriers, CD3+ T-cells
      (approximately 20% of the mononuclear cell infiltrate) were plentiful in choroid
      plexuses and commonly seen around blood vessels. The CD138+ plasma cells were
      restricted to the choroid plexus and stria medullaris of diseased MRL-lpr mice.
      Although accounting for less than 1% of the total cell infiltrate, CD19+IgM+ B
      cells increased with age in brains of MRL-lpr mice. Severe mononuclear cell
      infiltration was accompanied by splenomegaly and retarded brain growth. The
      results obtained support the hypothesis of progressive neurodegeneration as a
      consequence of leukocyte infiltration and intrathecal autoantibody synthesis.
      Further characterization of neuroactive antibodies and their targets may
      contribute to a better understanding of brain atrophy and behavioral dysfunction
      in the MRL model, and potentially in NP-SLE.

PMID- 16904196
TI  - Otoacoustic emissions in children with otitis media with effusion.
AB  - OBJECTIVES: Otoacoustic emissions (OAE) are transmitted from the cochlea to the
      ear canal via the middle ear and the transmission properties of the middle ear
      directly influence OAE characteristics. The purpose of this study was to
      establish the mechanisms of changes occurred in middle ear by tympanometric,
      audiometric and OAE examination. METHODS: Audiometric and tympanometric
      examination were performed and otoacoustic emissions were recorded from 22 normal
      ears and 52 ears with middle ear effusions and repeated 3 months later. RESULTS:
      Results of the air conduction in study group were significantly different from
      the control group and we found significant recovery in 3 months. When we analysed
      the DPOAE evaluation results in our study, some of the DPOAE parameters were
      found to be different between the control and the study group at low frequencies.
      Changes in the amplitude, especially at low frequencies, were statistically
      significant after 3 months. CONCLUSION: The results of this study revealed that
      measurement of otoacoustic emissions, especially distortion product otoacoustic
      emissions, is helpful in evaluating the condition of middle ear during the
      treatment.

PMID- 16904197
TI  - PDZ-domain arrays for identifying components of GPCR signaling complexes.
AB  - Many G-protein-coupled receptors (GPCRs) modulate the activity of multiple
      effectors. Yet, despite this apparent promiscuity, signaling in the context of
      differentiated cells is often highly specific. This specificity is attributable
      to the formation of cell-type-specific signaling complexes that are held together
      by scaffolding proteins, many of which contain one or more PDZ domains.
      Identifying the set of potential interactions among GPCRs, other signaling
      molecules and these scaffolding proteins is essential for understanding
      physiological signaling processes. A recent article describes an elegantly simple
      PDZ-domain array that can identify potential interacting partners of GPCRs and
      other signaling molecules.

PMID- 16904198
TI  - Copious production of SARS-CoV nucleocapsid protein employing codon optimized
      synthetic gene.
AB  - The severe acute respiratory syndrome coronavirus (SARS-CoV) nucleocapsid protein
      (NP) is one of the predominant antigenic protein and the most abundant shed
      antigen throughout the SARS-CoV infection. This feature makes it a suitable
      molecular target for diagnostic applications. In this study the full length codon
      optimized NP gene and its subfragment gene segment was cloned in a bacterial
      expression vector. The full length NP could be expressed in E. coli at very high
      level within inclusion bodies. The inclusion bodies were successfully
      solubilized, purified under denaturing conditions employing IMAC column and
      refolded. The non-glycosylated NP was used to immunize mice for hybridoma
      development. The polyclonal antiserum from animals immunized with this
      recombinant NP protein was found to specifically recognize the NP and its
      subfragments, thus demonstrating the immunogenic nature of the recombinant
      protein. The NP antigen or a subfragment could be useful for developing a
      sensitive serum diagnostic assay to monitor SARS-CoV outbreaks by detecting the
      early human anti-SARS antibodies. In addition, the availability of the NP
      fragments could facilitate epitope mapping of anti-NP monoclonals for identifying
      suitable sandwich pairs.

PMID- 16904199
TI  - Mismatch between anxiety status and morphometric parameters in the amygdala and
      bed nucleus of the stria terminalis.
AB  - Aging is associated with behavioral changes, including increased anxiety. In this
      study we confirmed a hyperanxious status in aged animals, measured in the
      elevated-plus maze and in the acoustic startle. Subsequently, we searched for age
      related changes in the volume and cell numbers in the amygdala or in the bed
      nucleus of the stria terminalis, but failed to detect gross structural changes in
      these two brain areas, both implicated in emotionality.

PMID- 16904200
TI  - Gender biased differential alternative splicing patterns of the transcriptional
      cofactor CA150 gene in Schistosoma mansoni.
AB  - The complex molecular systems involved in the process of sex-differentiation and
      fertility in Schistosoma mansoni have not yet been completely described. Using a
      4608-element cDNA microarray, we have now determined 90 and 139 genes with
      significantly (q-value</=0.06) higher expression levels in adult males and
      females, respectively. Eight out of eleven (73%) selected transcripts had their
      differential expression levels validated by real-time RT-PCR. One of these
      transcripts was extended by RT-PCR and was shown to span the intronic region
      between exons 9 and 11 of the S. mansoni CA150 gene, a transcriptional cofactor
      known in humans to interact with both RNA polymerase II and the spliceosome
      complex. The longer transcript probably represents a novel isoform of S. mansoni
      CA150. Additionally, we obtained full-length sequences for three other isoforms
      of the SmCA150 gene, coding for proteins of different lengths and domain
      compositions. Semi-quantitative RT-PCR showed different expression ratios among
      these isoforms between male and female. Due to the role of CA150 in RNA
      transcription and processing, we hypothesize that these differential expression
      events may be important in the generation and maintenance of the different
      phenotypes between male and female.

PMID- 16904201
TI  - Renal atrial natriuretic peptide receptors binding properties and function are
      resistant to DOCA-salt-induced hypertension in rats.
AB  - Atrial natriuretic peptide receptor types A (NPR-A) and C (NPR-C) binding
      properties and functional characteristics in renal glomeruli have been
      investigated in deoxycorticosterone acetate (DOCA)-treated hypertensive Wistar
      Kyoto (WKY) rats and their respective controls. We found that DOCA administration
      had no significant effect on the maximum binding capacity or the affinity of
      renal NPR-A and NPR-C. NPR-C is involved in the regulation of cAMP production.
      Our results indicate that the cAMP production by NPR-C is not altered in DOCA
      induced hypertension, since ANP(1-28), CNP(1-22) and C-ANP, which specifically
      bind to NPR-C, show a similar inhibitory effect on cAMP production stimulated by
      the physiological agonist histamine in glomeruli from DOCA-treated rats and
      controls. Finally, we have found that DOCA-induced hypertension does not modify
      NPR-A or NPR-C expression in rat glomerular membranes. These findings indicate
      that NPR-A and NPR-C binding properties and NPR-C-mediated inhibition of cAMP
      generation remain unaltered in DOCA-treated rats.

PMID- 16904202
TI  - Calcitonin gene-related peptide regulates the expression of vascular endothelial
      growth factor in human HaCaT keratinocytes by activation of ERK1/2 MAPK.
AB  - Psoriasis is a chronic disease characterized by abnormal epidermal proliferation,
      inflammation and angiogenesis. The pathogenetic process resulting in
      hypervascularity remains to be further investigated. It has been reported that a
      potent angiogenic factor, vascular endothelial growth factor (VEGF) is
      overexpressed in psoriatic epidermis and that the level of calcitonin gene
      related peptide (CGRP) is elevated in psoriasis lesions and CGRP-containing
      neuropeptide nerve fibers are denser in the psoriatic epidermis. We hypothesized
      that CGRP might regulate the expression of VEGF by human keratinocytes. VEGF
      expression in the CGRP-treated human keratinocytes was investigated and the CGRP
      signaling pathways were examined with respect to VEGF expression. The mRNA and
      protein levels of VEGF by CGRP were increased in a concentration-dependent
      manner. However, this increase was abrogated by pretreatment with an
      extracellular signal-regulated kinase (ERK) inhibitor PD98059. The CGRP-mediated
      VEGF induction was also effectively inhibited by a pretreatment with the CGRP
      receptor antagonist CGRP 8-37. In addition, CGRP treatment induced rapid
      phosphorylation of ERK1/2, PD98059 and CGRP 8-37 were able to inhibit CGRP
      induced ERK1/2 phosphorylation. These results suggest that CGRP regulates the
      expression of VEGF through the CGRP receptor and ERK1/2 MAPK signaling pathway in
      human HaCaT keratinocytes.

PMID- 16904203
TI  - Biological microarray interpretation: the rules of engagement.
AB  - Gene expression microarrays are now established as a standard tool in biological
      and biochemical laboratories. Interpreting the masses of data generated by this
      technology poses a number of unusual new challenges. Over the past few years a
      consensus has begun to emerge concerning the most important pitfalls and the
      proper ways to avoid them. This review provides an overview of these ideas,
      beginning with relevant aspects of experimental design and normalization, but
      focusing in particular on the various tools and concepts that help to interpret
      microarray results. These new approaches make it much easier to extract
      biologically relevant and reliable hypotheses in an objective and reasonably
      unbiased fashion.

PMID- 16904204
TI  - p120 catenin and phosphorylation: Mechanisms and traits of an unresolved issue.
AB  - p120 catenin is a scaffold protein that interacts with cadherin cytoplasmic
      domain and acts as a crucial component of the signalling that regulates the cycle
      of adherens junction formation and disassembly. Here, we review the nature of
      stimuli that modulate p120ctn function and are translated as serine/threonine and
      tyrosine phosphorylation events at this multisite substrate for a variety of
      protein kinases. We also highlight recent findings that tentatively link
      phosphorylation of p120ctn to its role as a signal integrator capable to
      influence the state of the cadherin adhesive bond, the cytoskeleton and cell
      motility.

PMID- 16904205
TI  - Increased stability of P21(WAF1/CIP1) mRNA is required for ROS/ERK-dependent
      pancreatic adenocarcinoma cell growth inhibition by pyrrolidine dithiocarbamate.
AB  - We present evidence that pyrrolidine dithiocarbamate (PDTC) inhibits growth of
      p53-negative pancreatic adenocarcinoma cell lines via cell cycle arrest in the S
      phase, while it has no effect on primary fibroblast proliferation. Growth
      inhibition of cancer cells is dependent on ROS and ERK1/2 induction as indicated
      by a significantly reduced PDTC-associated growth inhibition by the free radical
      scavenger N-acetyl-L-cysteine (NAC) or the MEK/ERK1/2 inhibitor (PD98059).
      Moreover, ERK1/2 induction is dependent on ROS production as demonstrated by a
      complete removal of PDTC-mediated ERK1/2 phosphorylation by NAC. p21(WAF1/CIP1)
      activation has a central role in growth inhibition by PDTC, as revealed by
      P21(WAF1/CIP1) silencing experiments with antisense oligonucleotide, and occurs
      via increased mRNA stability largely mediated by ROS/ERK induction. Conversely,
      PDTC does not affect P21(WAF1/CIP1) gene expression in primary fibroblasts,
      although it is able to activate p53 and the p53-regulated antioxidant SESN2.
      These results suggest that the resistance of fibroblasts to the cytotoxic action
      of PDTC may be related to the up-regulation of p53-dependent antioxidant genes.
      Finally, in vivo studies on PaCa44 cells subcutaneously xenografted in nude mice
      show that treatment with 100 or 200 mg/kg PDTC reduces of 30% or 60% the tumour
      volume, respectively, and does not cause any apparent form of toxicity.

PMID- 16904207
TI  - Effect of amiodarone treatment on outcome after direct current cardioversion in
      atrial fibrillation: should we cardiovert atrial fibrillation of longer duration.

PMID- 16904206
TI  - Myosin at work: motor adaptations for a variety of cellular functions.
AB  - Cells have evolved multiple mechanisms to overcome the effects of entropy and
      diffusion to create a highly ordered environment. For cells to function properly,
      some components must be anchored to provide a framework or structure. Others must
      be rapidly transported over long distances to generate asymmetries in cell
      morphology and composition. To accomplish long-range transport, cells cannot rely
      on diffusion alone as many large organelles and macromolecular complexes are
      essentially immobilized by the dense meshwork of the cytosol. One strategy used
      by cells to overcome diffusion is to harness the free energy liberated by ATP
      hydrolysis through molecular motors. Myosins are a family of actin based
      molecular motors that have evolved a variety of ways to contribute to cellular
      organization through numerous modifications to the manner they convert that free
      energy into mechanical work.

PMID- 16904208
TI  - Intimal dehiscence during endovascular treatment of thoracic aortic dissection.
AB  - Endovascular treatment of thoracic aortic pathology has become a valuable
      alternative therapeutic option to open surgery, however complications both during
      implantation and the postoperative period may occur. In this case report we
      present an intimal dehiscence during endovascular procedure. Diagnosis was made
      by transoesophageal echocardiography.

PMID- 16904209
TI  - Five-year outcomes after stenting of unprotected left main coronary artery
      stenosis in patients with normal left ventricular function.
AB  - BACKGROUND: We analyzed the long-term (5-year) outcome of patients treated with
      stenting for unprotected left main coronary artery (LMCA) stenosis. METHODS:
      Between January 1995 and September 2001, 187 consecutive patients with
      unprotected LMCA stenosis and normal left ventricular function underwent elective
      stenting. Patients were examined or interviewed after 1, 3 and 6 months, and
      every 4 months thereafter for the occurrence of major adverse cardiac events
      (MACE), including death, myocardial infarction (MI) and target lesion
      revascularization (TLR). RESULTS: The procedural success rate was 99.5%. During
      hospitalization, there were no deaths and only one stent thrombosis. Six-month
      angiography in 162 patients (follow-up rate, 86.6%) showed a restenosis rate of
      33.3%. During 5-year follow-up, there were 13 deaths (6 cardiac, 7 noncardiac)
      and 2 nonfatal MI. TLRs were required in 36 (20.9%) patients and new lesion
      revascularizations were required in 13 (5.0%) patients. At 1, 3 and 5 years, the
      cumulative probabilities for freedom from MACE were 79.9+/-1.8%, 77.5+/-2.5% and
      77.5+/-2.5%, respectively. CONCLUSION: The initial favorable outcomes of patients
      with normal left ventricular function after stenting of unprotected LMCA stenosis
      were sustained for up to 5 years.

PMID- 16904210
TI  - Angiosarcoma of the pericardium presenting as hemorrhagic pleuropericarditis,
      cardiac tamponade, and thromboembolic phenomena.

PMID- 16904211
TI  - Tai Chi: the Chinese ancient wisdom of an ideal exercise for cardiac patients.

PMID- 16904212
TI  - Lethal synchronization of multivessel instability in acute coronary syndrome.
AB  - Patients with acute coronary syndromes can display widespread coronary
      instability. We report a case presenting with ST segment elevation myocardial
      infarction and rapid progression to thrombosis of all major epicardial coronary
      arteries documented by angiography and at autopsy.

PMID- 16904213
TI  - Impact of weather and climate on the incidence of acute coronary syndromes.
AB  - BACKGROUND: First investigations of the interactions between weather and the
      incidence of acute myocardial infarctions date back to 1938. The early
      observation of a higher incidence of myocardial infarctions in the cold season
      could be confirmed in very different geographical regions and cohorts. While the
      influence of seasonal variations on the incidence of myocardial infarctions has
      been extensively documented, the impact of individual meteorological parameters
      on the disease has so far not been investigated systematically. Hence the present
      study intended to assess the impact of the essential variables of weather and
      climate on the incidence of myocardial infarctions. METHODS: The daily incidence
      of myocardial infarctions was calculated from a national hospitalization survey.
      The hourly weather and climate data were provided by the database of the national
      weather forecast. The epidemiological and meteorological data were correlated by
      multivariate analysis based on a generalized linear model assuming a log-link
      function and a Poisson distribution. RESULTS: High ambient pressure, high
      pressure gradients, and heavy wind activity were associated with an increase in
      the incidence of the totally 6560 hospitalizations for myocardial infarction
      irrespective of the geographical region. Snow- and rainfall had inconsistent
      effects. Temperature, Foehn, and lightning showed no statistically significant
      impact. CONCLUSIONS: Ambient pressure, pressure gradient, and wind activity had a
      statistical impact on the incidence of myocardial infarctions in Switzerland from
      1990 to 1994. To establish a cause-and-effect relationship more data are needed
      on the interaction between the pathophysiological mechanisms of the acute
      coronary syndrome and weather and climate variables.

PMID- 16904214
TI  - CYPHER versus TAXUS stent for bifurcation lesions beyond 30 days-long-term follow
      up results.

PMID- 16904215
TI  - Lyme carditis: persistent local delayed enhancement by cardiac magnetic resonance
      imaging.
AB  - Lyme borreliosis (LB) is the most common tick-born disease in the Northern
      Hemisphere. During early disseminated Lyme disease cardiac manifestation can
      occur. We report a case of isolated Lyme myocarditis with transitory total
      atrioventricular (AV)-block and myocardial necrosis indicated by a rise in
      Troponin-T (TNT). Antibiotic treatment resulted in complete resolution of the AV
      block, but a local epimyocardial contrast enhancement persisted as shown by
      cardiac magnetic resonance imaging (MRI).

PMID- 16904216
TI  - Diffuse coronary dilation in a young patient with LEOPARD syndrome.

PMID- 16904217
TI  - Phase shifts in the stoichiometry of rifamycin B fermentation and correlation
      with the trends in the parameters measured online.
AB  - Antibiotic fermentation processes are raw material cost intensive and the
      profitability is greatly dependent on the product yield per unit substrate
      consumed. In order to reduce costs, industrial processes use organic nitrogen
      substrates (ONS) such as corn steep liquor and yeast extract. Thus, although the
      stoichiometric analysis is the first logical step in process development, it is
      often difficult to achieve due to the ill-defined nature of the medium. Here, we
      present a black-box stoichiometric model for rifamycin B production via
      Amycolatopsis mediterranei S699 fermentation in complex multi-substrate medium.
      The stoichiometric coefficients have been experimentally evaluated for nine
      different media compositions. The ONS was quantified in terms of the amino acid
      content that it provides. Note that the black box stoichiometric model is an
      overall result of the metabolic reactions that occur during growth. Hence, the
      observed stoichiometric coefficients are liable to change during the batch cycle.
      To capture the shifts in stoichiometry, we carried out the stoichiometric
      analysis over short intervals of 8-16 h in a batch cycle of 100-200 h. An error
      analysis shows that there are no systematic errors in the measurements and that
      there are no unaccounted products in the process. The growth stoichiometry shows
      a shift from one substrate combination to another during the batch cycle. The
      shifts were observed to correlate well with the shifts in the trends of pH and
      exit carbon dioxide profiles. To exemplify, the ammonia uptake and nitrate uptake
      phases were marked by a decreasing pH trend and an increasing pH trend,
      respectively. Further, we find the product yield per unit carbon substrate to be
      greatly dependent on the nature of the nitrogen substrate. The analysis presented
      here can be readily applied to other fermentation systems that employ multi
      substrate complex media.

PMID- 16904218
TI  - Lipase-catalyzed transesterification of dihydrocaffeic acid with flaxseed oil for
      the synthesis of phenolic lipids.
AB  - Lipase-catalyzed transesterification reaction of dihydrocaffeic acid (DHCA) with
      flaxseed oil in organic solvent media was investigated. Using equal molar
      concentration of DHCA and flaxseed oil, only phenolic monoacylglycerols were
      obtained with a transesterification yield (TY) of 18.9%. A 1:4 DHCA to flaxseed
      oil ratio resulted in the production of both phenolic mono and diacylglycerols,
      with TY of 39.6 and 27.8%, respectively. On the other hand, when 1:8 ratio of
      DHCA to flaxseed oil was used, the TY of phenolic diacylglycerols (46.0%) was
      higher than that of the phenolic monoacylglycerols (33.3%). The TY of phenolic
      diacylglycerols increased from 25.1 to 55.8%, when the ratio of the hexane/2
      butanone reaction medium was changed from 65:35 to 85:25 (v/v); however, the TY
      of phenolic monoacylglycerols decreased slightly from 34.0 to 31.8%. The relative
      proportion of the C(18:3)n-3 was higher in the phenolic mono and diacylglycerols,
      64.9 and 59.5%, respectively, as compared to the original flaxseed oil, 53.1%.
      The radical scavenging ability of phenolic lipids was significant; however, it
      was about half than that of alpha-tocopherol.

PMID- 16904219
TI  - Functional and antigenic analyses of the 1918 influenza virus haemagglutinin
      using a recombinant vaccinia virus expression system.
AB  - The influenza pandemic of 1918 caused unprecedented levels of morbidity and
      mortality in its 12-month period of circulation around the globe. The
      haemagglutinin molecule has been shown to affect the pathogenicity of some
      subtypes of influenza A viruses. Using a recombinant vaccinia system that allowed
      expression of the 1918 influenza haemagglutinin, we performed functional assays
      to assess the glycoprotein's involvement in determining the high pathogenicity of
      the 1918 virus. We show that in respect of expression levels, proteolytic
      processing, receptor-binding, membrane fusion and antigenic properties, the
      haemagglutinin of the 1918 virus is unremarkable when compared with the
      haemagglutinins of other 'early' H1 influenza viruses. This suggests that whilst
      the 1918 haemagglutinin, as a new/novel antigen in the human population, was
      responsible for the influenza pandemic its functions per se were not responsible
      for the high mortality and acute symptoms experienced by patients infected with
      the 1918 influenza virus.

PMID- 16904220
TI  - A dual-ligand approach for enhancing targeting selectivity of therapeutic
      nanocarriers.
AB  - Conjugation of ligands to nano-scale drug carriers targeting over-expressed cell
      surface receptors is a promising approach for delivery of therapeutic agents to
      tumor cells. However, most commonly utilized ligands are directed at receptors
      expressed not only on target cells but also on other cells in the body, leading
      to unintended uptake in these off-target cells. In this study, a novel, dual
      ligand approach is reported, which targets tumor cells while sparing off-target
      cells by exploiting the fact that tumor cells typically over-express multiple
      types of surface receptors. This approach was tested in the human KB cell line,
      which over-expresses both folate receptor (FR) and the epidermal growth factor
      receptor (EGFR). Liposomal nanocarriers loaded with doxorubicin and bearing
      controlled numbers of both folic acid and a monoclonal antibody against the EGFR
      were designed. Cytotoxicity was used to determine targeting selectivity of the
      designed carriers in vitro by utilizing KB cells expressing both FR and EGFR and
      off-target control cells in which one or both receptors were blocked. The data
      demonstrates that nanocarriers can be designed to achieve toxicity only when all
      targeted receptors are available, providing an approach to improve selectivity
      over current single-ligand approaches.

PMID- 16904221
TI  - Tracking the in vivo fate of recombinant polypeptides by isotopic labeling.
AB  - We report a method to incorporate a stable isotope (13C) and a radioactive
      isotope (14C) into a recombinant polypeptide during Escherichia coli culture in
      M9 minimal medium supplemented with universally labeled 13C- or 14C-labeled
      glucose. We chose a thermally responsive elastin-like polypeptide (ELP) as a
      model polypeptide for this study because of its utility in various biotechnology
      applications such as drug delivery and tissue engineering. High cell densities
      were obtained by step-wise adaptation of E. coli to M9 medium in addition to
      supplementing the medium with trace elements that facilitated growth of E. coli.
      Furthermore, an optimal concentration of isopropyl-beta-d-thiogalactopyranoside
      was determined for induction of ELP expression to achieve high yield (mg/L
      culture) of the ELP. The incorporation of carbon isotopes was stoichiometrically
      related to the ratio of labeled glucose to unlabeled glucose in the culture
      medium. The isotope-labeled variants retained the physicochemical properties of
      the unlabeled ELP, specifically its temperature dependent aggregation behavior.
      As an example of the utility of this method, the in vitro stability of 14C
      labeled ELP in PBS and mouse serum was conveniently quantified by SDS-PAGE and
      autoradiography. In addition, the in vivo stability of the 14C-labeled ELP in
      plasma was determined along with its plasma pharmacokinetics.

PMID- 16904222
TI  - Electronic speckle pattern interferometry: a novel non-invasive tool for studying
      drug transport rate through free films.
AB  - In this work, Electronic Speckle Pattern Interferometry (ESPI) is presented as a
      non-invasive tool to study drug transport in controlled release systems. ESPI is
      shown to be a feasible tool to measure drug film permeability via comparison with
      an ordinary diaphragm cell. A specially designed cuvette was used in the release
      study: the polymeric film separated the donor and the receiving chambers of the
      cuvette to create a diffusion cell with no mixing in the two chambers. Thus, the
      cuvette mimicked a coated system immersed in a stagnant bulk liquid.
      Concentration profile data were obtained for the two compartments. Using these
      data, it was possible to visually discriminate between a film subject only to
      diffusion and a film subject to diffusion as well as osmotic effects. Moreover,
      using the concentration profile data collected at different time intervals, it
      was possible to follow the film properties in terms of drug permeability, thus
      studying how drug permeability depended on drug concentration. Compared to other
      measuring techniques, ESPI offers the advantages that no invasive measurements
      are needed, and that no sampling and calibration are required. Furthermore, the
      permeability can be measured with no influence of mass transfer in the boundary
      layers.

PMID- 16904223
TI  - Clinical effects of mechanical periodontal therapy in type 2 diabetic patients.

PMID- 16904224
TI  - A randomized controlled trial comparing ligation and sclerotherapy as emergency
      endoscopic treatment added to somatostatin in acute variceal bleeding.
AB  - BACKGROUND/AIMS: The currently recommended treatment for acute variceal bleeding
      is the association of vasoactive drugs and endoscopic therapy. However, which
      emergency endoscopic treatment combines better with drugs has not been clarified.
      This study compares the efficacy and safety of variceal ligation and
      sclerotherapy as emergency endoscopic treatment added to somatostatin. METHODS:
      Patients admitted with acute gastrointestinal bleeding and with suspected
      cirrhosis received somatostatin infusion (for 5 days). Endoscopy was performed
      within 6h and those with esophageal variceal bleeding were randomized to receive
      either sclerotherapy (N=89) or ligation (N=90). RESULTS: Therapeutic failure
      occurred in 21 patients treated with sclerotherapy (24%) and in nine treated with
      ligation (10%) (RR=2.4, 95% CI=1.1-4.9). Failure to control bleeding occurred in
      15% vs 4%, respectively (P=0.02). Treatment group, shock and HVPG >16 mmHg were
      independent predictors of failure. Side-effects occurred in 28% of patients
      receiving sclerotherapy vs 14% with ligation (RR=1.9, 95% CI=1.1-3.5), being
      serious in 13% vs 4% (P=0.04). Six-week survival probability without therapeutic
      failure was better with ligation (P=0.01). CONCLUSIONS: The use of variceal
      ligation instead of sclerotherapy as emergency endoscopic therapy added to
      somatostatin for the treatment of acute variceal bleeding significantly improves
      the efficacy and safety.

PMID- 16904225
TI  - Quantification of hepatitis B virus covalently closed circular DNA in patients
      with hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: This study aimed to measure the intrahepatic total hepatitis B
      virus (HBV) DNA and covalently closed circular DNA (cccDNA) levels in tumor and
      non-tumor tissues in hepatocellular carcinoma (HCC) patients. METHODS:
      Intrahepatic total HBV DNA and cccDNA were measured in 25 HCC patients (21
      hepatitis B surface antigen [HBsAg]-positive and 4 HBsAg-negative) by the Invader
      assay. RESULTS: A low level of intrahepatic HBV DNA was detectable in all HBsAg
      negative patients. For HBsAg-positive patients, the intrahepatic total HBV DNA
      levels in the tumor and non-tumor tissues were comparable (P=0.903). However, the
      tumor tissues had significantly higher levels of cccDNA (0.35 vs. 0.16
      copies/cell, P=0.030) and higher proportion of intrahepatic HBV DNA in the form
      of cccDNA (100% vs. 84%, P=0.004) than the non-tumor tissues. Seventeen out of 21
      (81%) tumor tissues had intrahepatic HBV DNA solely in cccDNA form. Analysis of
      HBV mRNA expression indicated that HBV replication appeared to be lower in the
      tumor tissues than the non-tumor tissues. CONCLUSIONS: Compared to the non-tumor
      tissues, the levels of HBV replication in the tumor tissues appeared to be lower,
      and cccDNA was the predominant form of HBV DNA in the tumor tissues.

PMID- 16904227
TI  - Shall I compare thee to a GM potato?
AB  - A fundamental issue in the safety assessment of genetically modified crops is the
      question of whether unintentional changes have occurred in the crop plant as a
      consequence of the genetic modification. This question was addressed recently by
      using a powerful metabolite fingerprinting and metabolite profiling method to
      assess whether genetically modified potatoes are substantially similar to their
      corresponding conventional cultivars.

PMID- 16904228
TI  - The cis-Golgi Drosophila GMAP has a role in anterograde transport and Golgi
      organization in vivo, similar to its mammalian ortholog in tissue culture cells.
AB  - The Golgi microtubule-associated protein of 210kDa (GMAP-210) has been shown to
      play a role in the assembly and maintenance of the Golgi apparatus in mammalian
      tissue culture cells. To develop a genetic model to study the function of GMAP
      210 in vivo, we identified its closest relative in Drosophila melanogaster,
      dGMAP. We show that the dGMAP gene encodes two alternatively spliced transcripts,
      only one of which is translated into a protein product. To gain insight into the
      role of dGMAP, we generated a polyclonal antibody and investigated the protein
      distribution during development. This gene is ubiquitously expressed during
      embryonic and larval development with the highest level in polar cells, gut and
      salivary glands. We further show that dGMAP is present in the Golgi apparatus,
      and using electron microscopy of salivary glands, we observed a preferential
      localization at the cis side and at the rims of the Golgi stacks. Finally, we
      demonstrate that overexpression of dGMAP in salivary glands impairs Golgi
      architecture and function, whereas RNAi-mediated depletion of dGMAP does not
      induce any structural modification of the Golgi apparatus, and anterograde
      transport is seemingly unaffected. Altogether our results suggest that dGMAP is
      the ortholog of mammalian GMAP-210.

PMID- 16904229
TI  - Biotransformation of hyoscyamine into scopolamine in transgenic tobacco cell
      cultures.
AB  - Hyoscyamine-6beta-hydroxylase (H6H) catalyses the conversion of hyoscyamine into
      its epoxide scopolamine, a compound with a higher added value in the
      pharmaceutical market than hyoscyamine. We report the establishment of tobacco
      cell cultures carrying the Hyoscyamus muticus h6h gene under the control of the
      promoter CAMV 35S. The cell cultures were derived from hairy roots obtained via
      genetically modified Agrobacterium rhizogenes carrying the pRi and pLAL21
      plasmids. The cultures were fed with hyoscyamine, and 4 weeks later the amount of
      scopolamine produced was quantified by HPLC. The transgenic cell suspension
      cultures showed a considerable capacity for the bioconversion of hyoscyamine into
      scopolamine, and released it to the culture medium. Although the scale-up from
      shake-flask to bioreactor culture usually results in reduced productivities, our
      transgenic cells grown in a 5-L turbine stirred tank reactor in a batch mode
      significantly increased the scopolamine accumulation.

PMID- 16904230
TI  - Effect of salinity on root-nodule conductance to the oxygen diffusion in the
      Cicer arietinum-Mesorhizobium ciceri symbiosis.
AB  - Nodule conductance to O2 diffusion has been involved as a major factor of the
      inhibition of N2 fixation by soil salinity that severely reduces the production
      of grain legumes. In order to determine the effect of this constraint on the
      nodule conductance, oxygen uptake by the nodulated roots of Cicer arietinum was
      measured by recording the concentration of O2 as a function of pO2 in a gas-tight
      incubator. After germination and inoculation with the strain Mesorhizobium ciceri
      UPMCa7, the varieties Amdoun 1 and INRAT 93-1 were hydroponically grown in a
      glasshouse on 1L glass bottles filled with nutrient solution containing 25 mM
      NaCl. Salinity induced a marked decrease in shoot (30% versus 14%), root (43%
      versus 20%), and nodule biomass (100% versus 43%) for Amdoun 1 relative to INRAT
      93-1. Although salinity completely prevented nodule formation in the sensitive
      variety Amdoun 1, nodule number and biomass were higher in the first than in the
      second variety in the absence of salt. This effect was associated with a
      significantly higher O2 uptake by nodulated root (510 versus 255 micromol O2
      plant(-1)h(-1)) and nodule conductance (20 versus 5 microm s(-1)) in Amdoun 1
      than in INRAT 93-1. Salinity did not significantly change the nodule conductance
      and nodule permeability for INRAT 93-1. Thus, the salt tolerance of this variety
      appears to be associated with stability in nodule conductance and the capacity to
      form nodules under salt constraint.

PMID- 16904231
TI  - Variation in indole-3-acetic acid transport and its relationship with growth in
      etiolated lupin hypocotyls.
AB  - The relationship between the variation in polar auxin transport (PAT) and
      elongating growth in etiolated Lupinus albus hypocotyls was investigated.
      Parameters of auxin transport, such as the amount transported, intensity of the
      transport and sensitivity to 1-N-naphthylphthalamic acid (NPA) inhibition were
      measured in isolated sections from different sites (apical, middle and basal)
      along the hypocotyls in seedlings of different ages. Auxin transport was studied
      by applying radioactive indole-3-acetic acid (IAA) to upright and inverted
      sections. Basipetal transport was much higher than acropetal and very sensitive
      to NPA inhibition, which indicates that transport is polarized. Polarity was
      expressed as the NPA-induced inhibition and the basipetal/acropetal ratio. As a
      rule, both the amount of IAA transported and the polarity varied with the age of
      the seedlings, with values increasing from 3 to 5d and then decreasing. Both
      parameters were higher in apical (where most growth is localized) than in middle
      and basal regions, although this longitudinal gradient tended to disappear with
      aging as hypocotyl growth slowed and finally ceased. The application of NPA did
      not modify hypocotyl elongation in 5-d-old intact seedlings. Derooting of the
      seedlings drastically reduced elongation in the control, while NPA partially
      restored the growth, which suggests that NPA induces an increase in auxin in the
      elongation region. These results suggest that a basipetally decreasing gradient
      in PAT along the hypocotyl, which changes with age, may be responsible for auxin
      distribution pattern controlling growth.

PMID- 16904232
TI  - Constitutive expression of an endoplasmic reticulum small heat shock protein
      alleviates endoplasmic reticulum stress in transgenic tomato.
AB  - To explore the function of endoplasmic reticulum-located small heat-shock
      proteins (ER-sHSPs) in ER stress, a putative ER-sHSP cDNA (the driven protein was
      named as LeHSP21.5 with GenBank accession No. AB026983) was isolated from tomato
      (Lycopersicon esculentum). Fractionation of the crude microsomes by isopycnic
      sucrose-gradient centrifugation revealed that LeHSP21.5 was distributed on a
      density corresponding to the fractions with a higher activity of ER marker
      enzyme, suggesting the localization of LeHSP21.5 in the ER. Overexpressing
      LeHSP21.5 in transgenic tomato plants (L. esculentum var. Zhongshu 4) greatly
      attenuated the lethal effect of tunicamycin on tomato seedlings. Moreover, under
      the tunicamycin treatment, transcripts of BiP, PDI and calnexin in transgenic
      tomato plants accumulated to a less level than those in non-transgenic tomato
      plants. These results suggest that LeHSP21.5 can function to alleviate the
      tunicamycin-induced ER stress.

PMID- 16904233
TI  - Changes in leaf cuticular waxes of sesame (Sesamum indicum L.) plants exposed to
      water deficit.
AB  - Sesame (Sesamum indicum L.) is one of the most important oilseed crops, having
      seeds and oil that are highly valued as a traditional health food. The objective
      of this study was to evaluate leaf cuticular wax constituents across a diverse
      selection of sesame cultivars, and the responses of these waxes to drought
      induced wilting. Water-deficit was imposed on 18 sesame cultivars by withholding
      irrigation for 15d during the post-flowering stage, and the effect on seed yield
      and leaf waxes compared with a well-watered control. Leaf cuticular waxes were
      dominated by alkanes (59% of total wax), with aldehydes being the next-most
      abundant class. Compared to well-irrigated plants, drought treatment caused an
      increase in wax amount on most cultivars, with only three cultivars having a
      notable reduction. When expressed as an average across all cultivars, drought
      treatment caused a 30% increase in total wax amount, with a 34% increase in total
      alkanes, a 13% increase in aldehydes, and a 28% increase in the total of
      unknowns. In all cultivars, the major alkane constituents were the C27, C29, C31,
      C33, and C35 homologs, whereas the major aldehydes were the C30, C32, and C34
      homologs, and drought exposure had only minor effects on the chain length
      distribution within these and other wax classes. Drought treatments caused a
      large decrease in seed yield per plant, but did not affect the mean weight of
      individual seeds, showing that sesame responds to post-flowering drought by
      reducing seed numbers, but not seed size. Seed yield was inversely correlated
      with the total wax amount (-0.466*), indicating that drought induction of leaf
      wax deposition does not contribute directly to seed set. Further studies are
      needed to elucidate the ecological role for induction of the alkane metabolic
      pathway by drought in regulating sesame plant survival and seed development in
      water-limiting environments.

PMID- 16904234
TI  - Production of potato intraspecific somatic hybrids with improved tolerance to PVY
      and Pythium aphanidermatum.
AB  - Somatic hybridization can be an interesting alternative for the selection of
      heterozygous and vigorous potato plants through combination of dihaploid genomes.
      The resulting hybrids can harbour interesting characters and thus can be used in
      agriculture if they are in agreement with agronomic criteria. In this report, we
      used an intraspecific somatic hybridization technique for the production of
      tetraploid potato lines. Two parental combinations were used in protoplast
      electrofusion procedure: Aminca-Cardinal and Cardinal-Nicola. The selection of
      somatic hybrids was based on in vitro plant vigour. Therefore, among the 75
      regenerated plants obtained from Aminca-Cardinal fusion, 3 putative hybrids were
      retained and 2 plant lines were selected among the 54 regenerated from the
      Cardinal-Nicola fusion. Heterosis was observed in the larger hybrid tuber size
      compared to the parents'. Our results also showed a precocity in the in vitro
      tuberization for the hybrids. Moreover, all of the regenerated putative hybrids
      were tetraploid (2n=4x=48 chromosomes). Isocitrate dehydrogenase and malate
      dehydrogenase isoenzyme analyses confirmed the hybrid nature of these lines. A
      molecular characterization performed by PCR amplification of simple sequence
      repeats and inter-simple sequence repeats confirmed that all these lines were
      somatic hybrids. The effect of potato virus Y infection on these hybrid lines was
      tested by mechanical inoculation of plants cultivated in a greenhouse. The
      majority displayed a reduction of infection rate associated with a delayed
      appearance of symptoms compared to the parents. Moreover, complete resistance was
      noted for one hybrid line (CN2). All hybrids also showed improved tolerance to
      Pythium aphanidermatum infection during tuber storage or after plant inoculation.

PMID- 16904235
TI  - Xyloglucanases in the interaction between saprobe fungi and the arbuscular
      mycorrhizal fungus Glomus mosseae.
AB  - We studied the production of xyloglucanase enzymes of pea and lettuce roots in
      the presence of saprobe and arbuscular mycorrhizal (AM) fungi. The AM fungus
      Glomus mosseae and the saprobe fungi Fusarium graminearum, Fusarium oxysporum
      126, Trichoderma harzianum, Penicillium chrysogenum, Pleurotus ostreatus and
      Aspergillus niger were used. G. mosseae increased the shoot and root dry weight
      of pea but not of lettuce. Most of the saprobe fungi increased the level of
      mycorrhization of pea and lettuce, but only P. chrysogenum and T. harzianum
      inoculated together with G. mosseae increased the dry weight of pea and lettuce
      respectively. The AM and saprobe fungi increased the production of xyloglucanases
      by plant roots. The level of xyloglucanase activities and the number of
      xyloglucanolytic isozymes in plants inoculated with G. mosseae and most of the
      saprobe fungi tested were higher than when both microorganisms were inoculated
      separately. The possible relationship between xylogucanase activities and the
      ability of AM and saprobe fungi to improve the dry weight and AM root
      colonization of plants was discussed.

PMID- 16904236
TI  - Hemorphin and hemorphin-like peptides isolated from dog pancreas and sheep brain
      are able to potentiate bradykinin activity in vivo.
AB  - Hemorphins are biologically active peptides, derived from hemoglobin, which
      presents a number of physiological activities. Proteolytic generation of these
      peptides is not fully understood; however, among their roles, is to provoke
      reduction on blood pressure. In this work, this particular biological effect was
      chosen as the monitor for the selection of mammalian vasoactive peptides. By
      combining high-performance liquid chromatography and mass spectrometry, including
      'de novo' sequencing, several hemorphin-like peptides were identified presenting
      bradykinin potentiating activity. Moreover, taking LVV-hemorphin-7 as model
      compound, we evaluated its biological effect on blood pressure of anaesthetized
      rats. By summarizing all the results, it is possible to present the hemorphins as
      a family of proteolytically generated peptides that are able to potentiate
      bradykinin activity in vivo.

PMID- 16904237
TI  - Differential processing of pro-neurotensin/neuromedin N and relationship to pro
      hormone convertases.
AB  - Neurotensin (NT) is synthesized as part of a larger precursor that also contains
      neuromedin N (NN), a six amino acid neurotensin-like peptide. NT and NN are
      located in the C-terminal region of the precursor (pro-NT/NN) where they are
      flanked and separated by three Lys-Arg sequences. A fourth dibasic sequence is
      present in the middle of the precursor. Dibasics are the consensus sites
      recognized and cleaved by endoproteases that belong to the recently identified
      family of pro-protein convertases (PCs). In tissues that express pro-NT/NN, the
      three C-terminal Lys-Arg sites are differentially processed, whereas the middle
      dibasic is poorly cleaved. Pro-NT/NN processing gives rise mainly to NT and NN in
      the brain, to NT and a large peptide ending with the NN sequence at its C
      terminus (large NN) in the gut and to NT, large NN and a large peptide ending
      with the NT sequence (large NT) in the adrenals. Recent evidence indicates that
      PC1, PC2 and PC5-A are the pro-hormone convertases responsible for the processing
      patterns observed in the gut, brain and adrenals, respectively. As NT, NN, large
      NT and large NN are all endowed with biological activity, the evidence reviewed
      here supports the idea that post-translational processing of pro-NT/NN in tissues
      may generate biological diversity.

PMID- 16904238
TI  - Neurotensin and growth of normal and neoplastic tissues.
AB  - Neurotensin (NT) is a brain-gut tridecapeptide that functions as a
      neurotransmitter/neuromodulator in the central nervous system (CNS) and as an
      endocrine agent in the periphery. NT has numerous physiologic effects on multiple
      organs. This review will focus on the effects of NT as a trophic factor for
      normal and neoplastic tissues. In this regard, NT may act as an endocrine agent
      or, in some instances, in a paracrine and/or autocrine fashion. These effects
      appear to be mediated predominantly through the G protein-coupled high-affinity
      NT receptor. However, some of the trophic effects may also be through the other
      two receptor subtypes, particularly the NT receptor type 3, which belongs to a
      recently identified family of sorting receptors. The signaling pathways mediating
      the effects of NT are multiple but most appear to activate the ERK signaling
      pathway, which then activates downstream transcription factors, ultimately
      leading to proliferation. NT may be a useful agent to enhance the growth of
      normal tissues such as the small bowel mucosa during periods of gut disuse or
      disease and, finally, the selective targeting of NT receptor subtypes on certain
      cancers may offer a novel strategy in the armamentarium of cancer
      chemotherapeutics.

PMID- 16904239
TI  - Inactivation of neurotensin and neuromedin N by Zn metallopeptidases.
AB  - The two related peptides neurotensin (NT) and neuromedin N (NN) are efficiently
      inactivated by peptidases in vitro. Whereas NT is primarily degraded by a
      combination of three Zn metallo-endopeptidases, namely endopeptidases 24.11,
      24.15 and 24.16, in all systems examined, NN is essentially inactivated by the Zn
      metallo-exopeptidase aminopeptidase M. In this paper we review the work that has
      led to the identification of the NT- and NN-degrading enzymes and to the
      purification and cloning of EP 24.16, a previously unidentified peptidase. We
      provide a brief description of the three NT-inactivating endopeptidases and of
      their specific and mixed inhibitors, some of them developed in the course of
      studying NT degradation. Finally, we review in vivo data obtained with these
      inhibitors that strongly support a physiological role for EP 24.11, 24.15 and
      24.16 in the termination of NT-generated signals and for aminopeptidase in
      terminating NN action. Knowledge of the NT and NN inactivation mechanisms offers
      the perspective to develop metabolically stable analogs of these peptides with
      potential therapeutic value.

PMID- 16904240
TI  - Different effects of ATP on the contractile activity of mice diaphragmatic and
      skeletal muscles.
AB  - Apart from acetyl-choline (Ach), adenosine-5'-trisphosphate (ATP) is thought to
      play a role in neuromuscular function, however little information is available on
      its cellular physiology. As such, effects of ATP and adenosine on contractility
      of mice diaphragmatic and skeletal muscles (m. extensor digitorum longa-MEDL)
      have been investigated in in vitro experiments. Application of carbacholine (CCh)
      in vitro in different concentrations led to pronounced muscle contractions,
      varying from 9.15+/-4.76 to 513.13+/-15.4 mg and from 44.65+/-5.01 to 101.46+/
      9.11 mg for diaphragm and MEDL, respectively. Two hundred micromolars of CCh in
      both muscles caused the contraction with the 65% (diaphragm) to 75% (MEDL) of
      maximal contraction force-this concentration was thus used in further
      experiments. It was found that application of ATP (100 microM) increased the
      force of diaphragmatic contraction caused by CCh (200 microM) from 335.2+/-51.4
      mg (n=21) in controls to 426.5+/-47.8 mg (n=10; P<0.05), but decreased the
      contractions of MEDL of CCh from 76.6+/-6.5mg (n=26) in control to 40.2+/-9.0mg
      (n=8; P<0.05). Application of adenosine (100 microM) had no effect on CCh-induced
      contractions of these muscles. Resting membrane potential (MP) measurements using
      sharp electrodes were done at 10, 20 and 30 min after the application of ATP and
      adenosine. Diaphragm showed depolarization from 75+/-0.6 down to 63.2+/-1.05,
      57.2+/-0.96 and 53.6+/-1.1 mV after 10, 20 and 30 min of exposition, respectively
      (20 fibers from 4 muscles each, P<0.05 in all three cases). Adenosine showed no
      effect on diaphragmatic MP. Both agents were ineffective in case of MEDL. The
      effects of ATP in both tissues were abolished by suramin (100 microM), a P2
      receptor antagonist, and chelerythrin (50 microM), a specific protein-kinase C
      (PKC) inhibitor, but were not affected by 1H-[1,2,4]-oxadiazolo-[4,3-alpha]
      quinoxalin-1-one (ODQ, 1 microM), a guanylyl-cyclase inhibitor, or by adenosine
      3,5-monophosphothioate (Rp-cAMP, 1 microM), a protein-kinase A (PKA) inhibitor.
      Besides the action on contractile activity, ATP (100 microM) led to a significant
      (P<0.001) depolarization of diaphragm muscle fibers from 74.5+/-2.3 down to 64+/
      2.1, 58.2+/-2.2 and 54.3+/-2.4 mV after 10, 20 and 30 min of incubation,
      respectively. Incubation of MEDL with the same ATP concentration showed no
      significant change of MP. Denervation of the muscles for 28 days led to a
      decrease of CCh-induced contractions of diaphragm down to 171.1+/-34.5mg (n=11,
      P<0.05), but increased the contractile force of MEDL up to 723.9+/-82.3mg (n=9,
      P<0.01). Application of ATP elevated the contractility of denervated diaphragm
      caused by CCh up to normal values (311.1+/-79.7 mg, n=6, P>0.05 versus control),
      but did not significantly affect of contractility of MEDL, which became 848.1+/
      62.7 mg (n=6). These results show that the effects of ATP on both diaphragmatic
      and skeletal muscles are mediated through P2Y receptors coupled to chelerytrin
      sensitive protein-kinase C.

PMID- 16904241
TI  - Nitric oxide-evoked cGMP production in Purkinje cells in rat cerebellum: an
      immunocytochemical and pharmacological study.
AB  - The cerebellar cells that account for glutamate-dependent cyclic GMP (cGMP)
      production, involving activation of the ionotropic glutamate receptors/nitric
      oxide synthase/soluble guanylyl cyclase pathway, are not fully established. In
      the present paper we have searched for the localisation of the cGMP response to
      the nitric oxide (NO) donor S-nitroso-penicillamine (SNAP 1muM), expected to
      generate local NO concentrations in the low nanomolar physiological range and
      evoking a cGMP response dependent on glutamate release and on the consequent
      activation of ionotropic glutamate NMDA/non-NMDA receptors, in cerebellar slices
      from adult rat. We have found that low concentration of exogenous NO evoked cGMP
      accumulation in Purkinje cells in an ionotropic glutamate receptor-dependent and
      tetrodotoxin-sensitive manner. Such immunocytochemical localisation appears
      consistent with functional evidence for physiologically relevant glutamate
      dependent cGMP production in Purkinje cells in rat cerebellar cortex.

PMID- 16904242
TI  - Poly(ADP-ribose) polymerase-1 inhibition protects the brain against systemic
      inflammation.
AB  - Poly(ADP-ribose) polymerase-1 (PARP-1) is involved in DNA repair, but its
      overactivation can induce cell death. Our aim was to investigate the role of PARP
      1 in activation of programmed cell death processes in the brain during systemic
      inflammation. Our data indicated that lipopolysaccharide (1mg/kgb.w., i.p.)
      evoked systemic inflammation enhanced PARP-1 activity in the mouse brain, leading
      to the lowering of beta-NAD(+) concentration, to translocation of apoptosis
      inducing factor from mitochondria to the nucleus, and to enhanced lipid
      peroxidation. Inhibitor of PARP-1, 3-aminobenzamide (30 mg/kgb.w., i.p.),
      protected the brain against prooxidative and cell death processes, suggesting
      involvement of PARP-1 in systemic inflammation-related processes in the brain.

PMID- 16904243
TI  - Alpha- and beta-secretase activity as a function of age and beta-amyloid in Down
      syndrome and normal brain.
AB  - Aged individuals with Down syndrome (DS) develop Alzheimer's disease (AD)
      neuropathology by the age of 40 years. The purpose of the current study was to
      measure age-associated changes in APP processing in 36 individuals with DS (5
      months-69 years) and in 26 controls (5 months-100 years). Alpha-secretase
      significantly decreased with age in DS, particularly in cases over the age of 40
      years and was stable in controls. The levels of C-terminal fragments of APP
      reflecting alpha-secretase processing (CTF-alpha) decreased with age in both
      groups. In both groups, there was significant increase in beta-secretase activity
      with age. CTF-beta remained constant with age in controls suggesting compensatory
      increases in turnover/clearance mechanisms. In DS, young individuals had the
      lowest CTF-beta levels that may reflect rapid conversion of beta-amyloid (Abeta)
      to soluble pools or efficient CTF-beta clearance mechanisms. Treatments to slow
      or prevent AD in the general population targeting secretase activity may be more
      efficacious in adults with DS if combined with approaches that enhance Abeta
      degradation and clearance.

PMID- 16904244
TI  - A TGF-beta1 polymorphism association with dementia and neuropathologies: the
      HAAS.
AB  - The transforming growth factor-beta1 (TGF-beta1) is involved in post-ischemic
      neuronal rescue and in beta-amyloid turn-over. We hypothesized that the risk for
      dementia and related neuropathologies is modified by the TGF-beta1 functional
      genetic variants. The association of the TGF-beta1+29T-->C polymorphism with
      dementia was examined in a sample of 261 cases and 491 controls from the Honolulu
      Asia Aging Study, including 282 subjects with autopsy data. Dementia was assessed
      in 1991 and 1994 by a multi-step protocol and standardized diagnostic criteria.
      The analysis was adjusted for demographic and vascular factors. Compared to the
      TT genotype, the TC and the CC genotypes were associated with a reduced risk for
      vascular dementia (OR(TC)=0.28, 95% confidence interval (CI): 0.1-0.9;
      OR(CC)=0.28, CI: 0.1-0.9), microinfarcts (OR(CC)=0.31, CI: 0.13-0.71) and
      cerebral amyloid angiopathy (OR(CC)=0.48, CI: 0.2-0.9). The CC genotype was
      associated with an increase risk of neocortical plaques (OR(CC)=4.34, CI: 1.6
      11.8). These preliminary data suggest that the TGF genetic variability may be
      important in the risk of vascular related dementia.

PMID- 16904245
TI  - Aseptic meningitis after vaccination with L-Zagreb mumps strain--virologically
      confirmed cases.

PMID- 16904246
TI  - Comparative estimations of 137Cs distribution in a boreal forest in northern
      Sweden using a traditional sampling approach and a portable NaI detector.
AB  - Field-portable detectors have been frequently used in routine monitoring and
      hazard assessment studies. However, there have been few thorough attempts to
      evaluate their potential as an alternative to the traditional procedure of
      collecting samples and analysing them in the laboratory. Thus, in this study the
      two approaches were compared in terms of their utility for monitoring (137)Cs
      activity in the Nyanget catchment in northern Sweden. The objectives were: (i) to
      determine the (137)Cs activity in soils associated with three types of
      vegetation, (ii) to map the geographical distribution of (137)Cs using the
      portable NaI detector connected to a GPS system (GDM-40), (iii) to identify
      (137)Cs anomalies in the catchment, and (iv) to compare the measurements obtained
      with the NaI detector and traditional sampling followed by laboratory analysis.
      Our results demonstrate that the GDM-40 has very good potential for making
      (137)Cs inventories and for detecting (137)Cs anomalies within large areas. The
      GDM-40 measurements identified differences between different hydrological areas
      that were not determined with the soil sampling method. The GDM-40 method is much
      faster than a traditional soil sampling method. However, soil sampling cannot be
      totally excluded because it is needed to calibrate the GDM-40. The agreement
      between the (137)Cs activity values obtained by the two approaches was 20% which
      is good in the field where so many factors vary.

PMID- 16904247
TI  - Measurement of the tensile strength of the ventral abdominal wall in comparison
      with scar tissue.
AB  - BACKGROUND: Paramedian laparotomies lead to incisional hernias in approximately
      30% of cases. In contrast, incisional hernias occur very rarely in the linea alba
      or the ventral abdominal wall. In this setting we investigated the difference
      between scar tissue and the non-incised abdominal wall tissue. METHODS: At the
      post mortem examination of 66 recently deceased individuals, accurately measured
      pieces of resected tissue from the linea alba, the anterior and the posterior
      rectus sheath, and scar tissue following median laparotomy, were exposed to
      tensile loads. FINDINGS: In the epigastric region the tissue ruptured at a mean
      horizontal load of 10.0 (SD 3.4) N/mm(2) in the linea alba and 6.9 (SD 2.5)
      N/mm(2) in scar tissue (P<0.001), and at a mean vertical load of 4.5 (SD 2.0)
      N/mm(2) in the linea alba and 3.3 (SD 1.6) N/mm(2) in scar tissue (P<0.05). In
      the hypogastric region as well, scar tissue was significantly less resistant in
      the main direction of load. INTERPRETATION: Scar tissue has a significantly
      lesser loading capacity than the intact ventral abdominal wall and therefore
      poses a permanent risk for herniation. For this reason, closure of the abdominal
      wall should be given due consideration and subjected to further investigation.
      Specifically, sustained reinforcement of scar tissue by means of suture
      techniques or non-absorbable sutures warrants further study. When constructing
      meshes for reinforcement of incisional hernias, the two-fold tensile load on the
      midline in horizontal direction as opposed to the craniocaudal direction must be
      taken into account.

PMID- 16904248
TI  - Factors affecting the ozone sensitivity of temperate European grasslands: an
      overview.
AB  - This overview of experimentally induced effects of ozone aims to identify
      physiological and ecological principles, which can be used to classify the
      sensitivity to ozone of temperate grassland communities in Europe. The analysis
      of data from experiments with single plants, binary mixtures and multi-species
      communities illustrates the difficulties to relate individual responses to
      communities, and thus to identify grassland communities most at risk. Although
      there is increasing evidence that communities can be separated into broad classes
      of ozone sensitivity, the database from experiments under realistic conditions
      with representative systems is too small to draw firm conclusions. But it appears
      that risk assessments, based on results from individuals or immature mixtures
      exposed in chambers, are only applicable to intensively managed, productive
      grasslands, and that the risk of ozone damage for most of perennial grasslands
      with lower productivity tends to be less than previously expected.

PMID- 16904249
TI  - Phytoextraction of excess soil phosphorus.
AB  - In the search for a suitable plant to be used in P phytoremediation, several
      species belonging to legume, vegetable and herb crops were grown in P-enriched
      soils, and screened for P accumulation potentials. A large variation in P
      concentrations of different plant species was observed. Some vegetable species
      such as cucumber (Cucumis sativus) and yellow squash (Cucurbita pepo var.
      melopepo) were identified as potential P accumulators with >1% (dry weight) P in
      their shoots. These plants also displayed a satisfactory biomass accumulation
      while growing on a high concentration of soil P. The elevated activities of
      phosphomonoesterase and phytase were observed when plants were grown in P
      enriched soils, this possibly contributing to high P acquisition in these
      species. Sunflower plants also demonstrated an increased shoot P accumulation.
      This study shows that the phytoextraction of phosphorus can be effective using
      appropriate plant species.

PMID- 16904250
TI  - Atmospheric deposition inputs and effects on lichen chemistry and indicator
      species in the Columbia River Gorge, USA.
AB  - Topographic and meteorological conditions make the Columbia River Gorge (CRG) an
      'exhaust pipe' for air pollutants generated by the Portland-Vancouver metropolis
      and Columbia Basin. We sampled fog, bulk precipitation, throughfall, airborne
      particulates, lichen thalli, and nitrophytic lichen distribution. Throughfall N
      and S deposition were high, 11.5-25.4 and 3.4-6.7 kg ha(-1) over 4.5 months at
      all 9 and 4/9 sites, respectively. Deposition and lichen thallus N were highest
      at eastern- and western-most sites, implicating both agricultural and urban
      sources. Fog and precipitation pH were frequently as low as 3.7-5.0. Peak NO(x),
      NH(3), and SO(2) concentrations in the eastern CRG were low, suggesting enhanced
      N and S inputs were largely from particulate deposition. Lichens indicating
      nitrogen-enriched environments were abundant and lichen N and S concentrations
      were 2x higher in the CRG than surrounding national forests. The atmospheric
      deposition levels detected likely threaten Gorge ecosystems and cultural
      resources.

PMID- 16904251
TI  - The social zeitgeber theory, circadian rhythms, and mood disorders: review and
      evaluation.
AB  - The social zeitgeber theory [Ehlers, C. L., Frank, E., & Kupfer, D. J. (1988).
      Social zeitgebers and biological rhythms. Archives of General Psychiatry, 45, 948
      952] offers an explanation of how life events trigger depressive episodes.
      According to this theory, life stress leads to mood episodes by causing
      disruptions in individuals' social routines and, in turn, their biological
      circadian rhythms. In this article, we review the literature pertaining to the
      social zeitgeber theory, as well as evidence that this theory may be applied to
      (hypo)manic episodes. Given the limited data supporting the social zeitgeber
      theory to date, we also evaluate whether circadian rhythm disruptions are
      triggered by an internal mechanism, such as an abnormality in one's pacemaker
      (the suprachiasmatic nucleus; SCN). We review these two theories in an attempt to
      understand the potential causes of circadian rhythm disruptions and affective
      episodes in individuals with unipolar and bipolar disorders. We also propose
      several areas of future research.

PMID- 16904252
TI  - Low plasma BDNF is associated with suicidal behavior in major depression.
AB  - Brain-derived neurotrophic factor (BDNF), the most abundant neurotrophin in the
      brain, has a known association with the pathophysiology of anxiety and
      depression. However, the role of BDNF in suicide has not been well investigated
      to date. This study examined plasma BDNF levels in 32 major depressive disorder
      (MDD) patients who had recently attempted suicide, 32 non-suicidal MDD patients,
      and 30 normal controls. The lethality of the suicide attempt was measured using
      the Risk-Rescue Rating (RRR) and Lethality Suicide Attempt Rating Scale (LSARS).
      The severity of depression was measured with the Hamilton Depression Rating Scale
      (HDRS). Plasma BDNF levels were measured by enzyme linked immunosorbent assay.
      BDNF levels were significantly lower in suicidal MDD patients (430.5+/-397.0
      pg/ml) than non-suicidal MDD patients (875.80+/-663.02 pg/ml) or normal controls
      (889.4+/-611.3 pg/ml) (F=6.682, p=0.002). The most suitable cut-off point of BDNF
      level between suicidal depression and non-suicidal depression groups was 444.58
      pg/ml. At this cut-off point, the sensitivity=68.7%, specificity=78.1%, positive
      predictive value=75.9%, and negative predictive value=71.4%. However, there was
      no significant difference in BDNF levels between the depressive control and
      normal control groups (p=0.996). LSARS and RRR did not reveal any significant
      correlations with BDNF levels in suicidal patients. In addition, BDNF levels were
      not different between fatal and non-fatal suicide attempts. These results suggest
      that reduction of plasma BDNF level is related to suicidal behavior in major
      depression and that BDNF level may be a biological marker of suicidal depression.

PMID- 16904253
TI  - Hypersexual behaviour, frotteurism and delusional jealousy in a young
      parkinsonian patient during dopaminergic therapy with pergolide: A rare case of
      iatrogenic paraphilia.
AB  - Neuropsychological and psychopathological modifications induced by dopaminergic
      drugs in patients with Parkinson's disease (PD) are invariably not taken into
      sufficient consideration by the neurologist. Among the former, modifications of
      sexual urges and behaviours are of particular importance with regard to severity
      and variety of clinical pictures. Although rare, such modifications may assume
      the connotations of an aberrant sexual behaviour with criminal implications, in
      line with a diagnosis of paraphilia. The authors report the case of a 51-year-old
      male PD patient who, after a few years of dopaminergic treatment with pergolide,
      developed a paraphilic disorder, consistent with DSM-IV TR diagnosis of
      frotteurism, and delusional jealousy. The patient presented mild motor impairment
      and lack of or negligible cognitive deterioration, thus providing evidence that
      these disorders are not typical of advanced PD. Pergolide was reduced and
      quetiapine, an atypical neuroleptic, was introduced with subsequent subsiding of
      the paraphilic disorder and improvement of delusional jealousy.

PMID- 16904254
TI  - The long-term effect of a composite resin restoration on proximal contact
      tightness.
AB  - OBJECTIVE: The aim of this study was to investigate changes in proximal contact
      tightness up to 6 months after the restorative treatment. MATERIALS AND METHODS:
      In a randomised clinical trial Class II composite resin restorations were placed
      in 52 patients. Proximal contact tightness was measured before, directly after,
      and 6 months after treatment. These data were analysed statistically using linear
      regression and t-tests. RESULTS: Proximal contacts, that increased in tightness
      as result of the treatment tend to loose tightness after a 6-months period but
      remain tighter than before treatment. Proximal contacts, that decreased after
      treatment hardly change after 6 months. CONCLUSIONS: A change in contact
      tightness after restorative treatment will not always remain stable over time.

PMID- 16904255
TI  - Comparative financial analysis of minimally invasive surgery to open surgery for
      small renal tumours < or =3.5 cm: a single institutional experience.
AB  - OBJECTIVE: We analysed total hospital costs by comparing minimally invasive
      surgery (MIS) procedures, such as laparoscopic cryoablation (LCA), laparoscopic
      partial nephrectomy (LPN), and hand-assisted laparoscopic nephrectomy (HALN),
      with conventional surgery. METHODS: Between March 2000 and July 2005, 184
      consecutive patients underwent surgery for a small, organ-confined renal tumour <
      or =3.5 cm in diameter. The distribution of patients among the surgical
      procedures was: HALN (n=53); LPN (n=20); open radical nephrectomy (ORN; n=20);
      open partial nephrectomy (OPN; n=71); and LCA (n=20). Total hospital costs were
      analysed for each procedure. RESULTS: Patients undergoing OPN at a mean age of
      58+/-13 yr were significantly younger those undergoing HALN, ORN, and LCA. The
      mean hospital length of stay in the LCA group (2.0+/-1.2 d) was shorter than all
      other groups (p<0.05). Higher surgical costs occurred with LCA, LPN, and HALN
      compared (p<0.05) with ORN and OPN. However, total financial costs were lower for
      LCA and HALN with more obvious differences between LCA and the other four groups.
      CONCLUSIONS: The costs of MIS remain competitive with traditional surgery.
      Although the surgical costs were higher, LCA had the lowest total hospital costs
      for the renal tumour < or =3.5 cm at our institution. Long-term oncologic
      efficacy studies will be needed to fully appreciate the cost-efficacy ratio of
      MIS.

PMID- 16904256
TI  - Detection of Escherichia coli 16S RNA and cytotoxic necrotizing factor 1 gene in
      benign prostate hyperplasia.
AB  - OBJECTIVES: Inflammation and occasionally necrosis is observed in the prostate
      tissue from patients with benign prostate hyperplasia (BPH). The etiology of
      prostatic inflammation/necrosis is unknown, but bacteria may be involved.
      MATERIALS AND METHODS: Retrospective analysis of archival prostate tissue samples
      collected during 1982-1997 was undertaken. Three hundred fifty-two specimens from
      patients with BPH obtained via transurethral resection of prostate (TURP) were
      studied for the presence of Escherichia coli 16S RNA and E. coli virulence factor
      genes: cytotoxic necrotizing factor (cnf1), alpha-hemolysin (hly), an
      autotransported protein (sat), and P fimbriae (papC). RESULTS: E. coli 16S RNA
      was detected in 12 (3%) samples and cnf1 gene in six (1.5%) samples, with two
      samples being positive for both markers. hly, sat, papC genes were not detected.
      Of 6 cnf1-positive samples, severe inflammation and necrosis were present in four
      and three samples, respectively. Of eight E. coli-positive/cnf1-negative samples,
      five showed signs of severe inflammation and two showed severe necrosis.
      CONCLUSIONS: A small proportion of patients with BPH undergoing TURP are positive
      for E. coli 16S RNA and cnf1 gene in the prostate tissue. Further studies are
      needed to show that particular E. coli genotypes are involved in the development
      of prostatic inflammation/necrosis in BPH.

PMID- 16904257
TI  - The poly(ADP-ribose) polymerase 1 interacts with Sry and modulates its biological
      functions.
AB  - Sry encodes a putative transcription factor that switches on testis
      differentiation during embryogenesis. Currently, the mechanism(s) by which Sry
      mediates such developmental process is still uncertain. To understand its gene
      regulation mechanism, we have utilized an in vitro affinity chromatography and
      proteomic strategy to identify and characterize Sry binding proteins from the
      mouse testis potentially involved in the formation of an Sry transcriptional
      complex(es). Our study has consistently identified the poly(ADP-ribose)
      polymerase 1 (PARP-1) as an Sry interactive protein. PARP-1 is expressed in mouse
      fetal gonads at the time of sex determination and co-localized with Sry in the
      nuclei of pre-Sertoli cells. PARP-1 could be co-immunoprecipitated with Sry in
      cultured cells. The interactive domains have been mapped to the HMG box of Sry
      and the zinc fingers of the PARP-1 protein, respectively. The Sry-PARP-1
      interaction is evolutionarily conserved and it interferes with the ability of Sry
      in binding to its consensus sequence. In the presence of its substrate, PARP-1
      poly(ADP-ribosyl)ates Sry and minimizes severely its DNA-binding activities. PARP
      1 represses Sry-mediated transactivation of a reporter gene in cultured cells.
      Hence, PARP-1 could modulate the regulatory function(s) of Sry on its target
      genes in this developmental pathway.

PMID- 16904258
TI  - Activated carbons and low cost adsorbents for remediation of tri- and hexavalent
      chromium from water.
AB  - Hexavalent chromium is a well-known highly toxic metal, considered a priority
      pollutant. Industrial sources of Cr(VI) include leather tanning, cooling tower
      blowdown, plating, electroplating, anodizing baths, rinse waters, etc. The most
      common method applied for chromate control is reduction of Cr(VI) to its
      trivalent form in acid (pH approximately 2.0) and subsequent hydroxide
      precipitation of Cr(III) by increasing the pH to approximately 9.0-10.0 using
      lime. Existing overviews of chromium removal only cover selected technologies
      that have traditionally been used in chromium removal. Far less attention has
      been paid to adsorption. Herein, we provide the first review article that
      provides readers an overview of the sorption capacities of commercial developed
      carbons and other low cost sorbents for chromium remediation. After an overview
      of chromium contamination is provided, more than 300 papers on chromium
      remediation using adsorption are discussed to provide recent information about
      the most widely used adsorbents applied for chromium remediation. Efforts to
      establish the adsorption mechanisms of Cr(III) and Cr(VI) on various adsorbents
      are reviewed. Chromium's impact environmental quality, sources of chromium
      pollution and toxicological/health effects is also briefly introduced.
      Interpretations of the surface interactions are offered. Particular attention is
      paid to comparing the sorption efficiency and capacities of commercially
      available activated carbons to other low cost alternatives, including an
      extensive table.

PMID- 16904260
TI  - Distribution patterns of natural radioactivity and delineation of anomalous
      radioactive zones using in situ radiation observations in Southern Tamil Nadu,
      India.
AB  - In situ radiation measurements in the beach sectors and adjacent hinterlands and
      along rivers in the interiors of southern peninsular India were carried out using
      a portable radiation survey meter. A very high intrinsic anomalous radioactivity
      >26microGy/h has been observed in the hinterlands within a fresh quarry and
      weathered boulders in the syenite rock body around Puttetti in the western
      Kanyakumari district of southern Tamil Nadu. Over the weathered hillocks in the
      hinterlands adjacent to the coast around Inayam, Kurumpanai and Midalam, the in
      situ radiation measurements have also exhibited high radioactivity ranging from 4
      to 22microGy/h which is significantly higher than the radiation exposure rates
      (RER) observed along the beach sectors at various locations from Chavara to
      Tuticorin (1-14microGy/h). The observed radiation levels are presumably the
      highest concentration in southern India and it is the first time that such a high
      intrinsic radiogenic source in the hinterlands is reported in southwest coast of
      India. It is also observed based on the laboratory analysis of samples and in
      situ radiation data that the rivers/channels in this region contain insignificant
      level of radioactivity concentration and hence they do not contribute much to the
      placer deposits on the beaches. The placer deposits associated with significant
      RER (both in situ observations as well as laboratory estimates from samples) in
      the beach sectors from Kadiapattanam to Inayam are inferred to be derived through
      the country rocks/weathered hillocks in the immediate hinterlands.

PMID- 16904259
TI  - Ocular hazards of the colors used during the festival-of-colors (Holi) in India-
      malachite green toxicity.
AB  - The objective of this study was to evaluate the nature of the colors used and
      their toxicity to the eye upon exposure to them during celebration of Holi (our
      festival-of-colors). Color powders and formulations were procured at random in
      and around Delhi during the festival. The green/bluish-green colors reported with
      the higher incidence of ocular toxicity were subjected for further evaluation.
      Eyewash fluid collected from the patients exposed to the colors was also
      subjected for analysis. This study was further extended to evaluate the corneal
      penetration of malachite green using goat cornea in perfusion chamber. In 16/18
      color samples collected, malachite green or 4-[(4-dimethylaminophenyl)-phenyl
      methyl]-N,N-dimethyl-aniline was detected at different concentrations. In the
      eyewash fluid of four patients, HPLC estimation confirmed the presence of
      malachite green at concentrations of 1.3, 0.18, 3.5 and 5.4 microg in 250 ml
      which was responsible for its reported toxicity. The in vitrotrans-corneal
      penetration studies did not show any detectable amount of malachite green in
      effluent fluid-in vitro tissue retention studies revealed that increasing the
      contact time increases tissue concentration. After 2 min of exposure, the tissue
      concentration was significantly higher. To conclude, malachite green was
      extensively used in our festival of Holi and has caused severe ocular irritation
      with epithelial defect upon exposure, though it did not penetrate through the
      cornea-further in vitro and in vivo studies are required on colors used in Holi.

PMID- 16904261
TI  - Kinetics of the degradation of 2-chlorophenol by ozonation at pH 3.
AB  - Prediction of byproduct distribution during ozonation is of importance to the
      design of treatment process. In this study, degradation products in direct
      ozonation of 2-chlorophenol in aqueous solution were identified by employing the
      chemical derivatization technique, specifically, silylation. Transient
      distribution of degradation products, in a semi-batch reactor under three ozone
      dosages were identified and determined by HPLC analysis. An empirical degradation
      pathway was proposed to describe the ozonation reaction. A mathematical protocol
      consisting of 11 equations and 12 rate constants was developed to solve and
      optimize the kinetic parameters. Modeling results revealed that the empirical
      pathway was capable of predicting the ozonation reaction at the beginning phase
      under a higher ozone dosage (e.g., greater than 6mg/L(g)). The degree of
      agreement between predicted and experimental data decreased as the ozone dosage
      decreased to 1.2mg/L(g). Results suggested that there was a dosage-dependent
      pathway in the direct ozonation of 2-chlorophenol.

PMID- 16904262
TI  - Palmitic acid-treated astrocytes induce BACE1 upregulation and accumulation of C
      terminal fragment of APP in primary cortical neurons.
AB  - High-fat diet is a significant risk factor for the development of Alzheimer's
      disease (AD). In addition, the AD brain is characterized by elevated levels of
      fatty acids as compared to that of healthy controls. Despite this, it is unclear
      how elevated levels of fatty acids are related to the pathogenesis of AD. The
      present study examines the role of saturated fatty acid, palmitic acid (PA), in
      causing BACE1 upregulation and consequent amyloidogenic processing of beta
      amyloid precursor protein (APP), one of the main characteristic signatures of AD
      pathology. Here, primary rat cortical neurons and astrocytes were treated with
      pathological concentration of PA. There was no change in the BACE1 levels in the
      rat cortical neurons treated directly with PA as compared to controls. The
      conditioned medium from PA-treated astrocytes, however, caused BACE1 upregulation
      in the cortical neurons. Moreover, there was a consequent increase in the
      cleavage of APP leading to the accumulation of the C-terminal fragment of APP
      (C99) in the cortical neurons. Co-treatment of neurons with 1,3-dimethyl urea
      (DMU), an antioxidant, decreased PA-induced upregulation in the levels of BACE1
      and C99. The present results establish an important role of saturated fatty acids
      in AD-associated amyloidogenesis through astroglia-mediated oxidative stress.

PMID- 16904264
TI  - A tactile stimulus applied to the leg improves postural stability in young, old
      and neuropathic subjects.
AB  - The purpose of this study was to determine whether the application of passive
      tactile cues to the lower limb could improve postural stability in healthy young
      controls, older people and people with diabetic peripheral neuropathy. Antero
      posterior sway was measured with eyes open and closed in 10 healthy young
      subjects (mean age 27 years, 5 male, 5 female), 10 older subjects without
      diabetic peripheral neuropathy (mean age 88 years, 2 male, 8 female) and 10
      subjects with diabetic peripheral neuropathy (mean age 65 years, 6 male, 4
      female) while a small piece of Velcro attached to a flexible mount was applied to
      three different sites on the leg (ankle, calf, and knee). Across all conditions,
      the mean sway of the neuropathic subjects was 93% greater than for the young
      subjects and 11% more than the older subjects. On average, subjects swayed 10%
      more with the eyes closed than with the eyes open. Each stimulus reduced sway,
      but the effect increased approximately in proportion to the height of the
      stimulus above the ankles (ankle 7.6%, calf 13.5%, knee 20.1% reduction compared
      to the no stimulus condition). This experiment demonstrates that a passive
      stimulus applied to the skin of the leg, which provides sensory information about
      body movement, significantly reduces body sway during standing. This applies to
      older subjects and subjects with peripheral neuropathy as well as healthy young
      subjects. These results have implications for novel approaches for improving
      stability in people with peripheral sensory loss.

PMID- 16904263
TI  - Possible involvement of BDNF release in long-lasting synapse formation induced by
      repetitive PKA activation.
AB  - For the analysis of the cellular mechanism underlying long-term synaptic
      plasticity, a model system that allows long-lasting pursuit is required.
      Previously we reported that, in hippocampal neurons under dissociated cell
      culture conditions, repeated (but not a single) transient activation of protein
      kinase A (PKA) led to an increase in the number of synapses that lasted >3 weeks,
      and hence we proposed that this phenomenon should serve as an appropriate model
      system. Here we report that repeated pulsatile application of brain-derived
      neurotrophic factor (BDNF) leads to persistent synapse formation equivalent to
      that after the repeated transient activation of PKA. A BDNF-scavenging substance
      applied concomitantly with PKA activation abolished the synapse formation. The
      release of BDNF upon PKA activation was confirmed by phosphorylation of TrkB.
      These results indicate that the release of BDNF is involved in the putative
      signaling cascade connecting PKA activation and synapse formation.

PMID- 16904265
TI  - Larval immersion tests with ivermectin in populations of the cattle tick
      Rhipicephalus (Boophilus) microplus (Acari: Ixodidae) from State of Sao Paulo,
      Brazil.
AB  - Larval immersion tests (LIT) with commercial formulation of ivermectin were
      carried out with larvae of two field populations of Rhipicephalus (Boophilus)
      microplus from commercial dairy farms of the State of Sao Paulo, Brazil and a
      susceptible strain (Porto Alegre) to differentiate resistant-suspected and
      susceptible strains. One of the populations tested (Barra Alegre) showed a LC(50)
      value significantly higher than the susceptible strain and a resistance ratio
      (CI95%) of 3.78 (3.47-4.12), leading to suspect that this population shows traces
      of resistance to ivermectin. Population Sao Francisco, with no records of
      ivermectin injections on cattle, showed no difference on the ivermectin response
      in relation to Porto Alegre strain characterizing it as susceptible. Although LIT
      is not yet recommended by FAO to diagnose resistance to acaricides, this
      technique was successful on the differentiation of resistance-suspected
      population and a susceptible strain and can be used to detect populations of R.
      (B.) microplus resistant to ivermectin. This is the first report of R. (B.)
      microplus resistant to ivermectin detected by an in vitro bioassay.

PMID- 16904266
TI  - Thrombostasin isoform frequency in a Central Texas field population of the horn
      fly, Haematobia irritans.
AB  - Thrombostasin is an anti-thrombin factor that plays a role in successful feeding
      of the horn fly, Haematobia irritans. It has been isolated and characterized from
      saliva, and polymorphisms in the gene coding sequence have been previously
      reported. In the present study, the thrombostasin gene was analyzed from 60,
      field-collected flies from Camp Stanley, Texas and the allele and genotype
      frequencies were compared with previously published data for an Alabama field
      collection and a Texas in vitro colony-reared collection. Significant differences
      in genotype frequency and extent of genotypic diversity observed between the
      Alabama and Camp Stanley field collections may be attributable to host genetic
      differences. In addition, bull calves that were phenotyped as either high- or low
      carriers were parasitized by horn flies that displayed a significantly different
      genotype distribution, supporting a possible explanation for horn fly host
      selection behavior, as evidenced by thrombostasin sequence analysis of 95
      additional horn flies collected from respective hosts.

PMID- 16904267
TI  - The efficiency of extracts of Dahlstedtia pentaphylla (Leguminosae,
      Papilionoidae, Millettiedae) on Boophilus microplus (Canestrini, 1887) in
      artificially infested bovines.
AB  - Tests were conducted to assess the efficiency of the roots of Dahlstedtia
      pentaphylla (Taub.) Burk. (Leguminosae, Papilionoideae, Millettiae) plant against
      infestations of Boophilus microplus (Canestrini, 1887). These tests were
      performed on 30 bovine animals in the Paraiba Valley, State of Sao Paulo, Brazil,
      divided into three groups (control, extract diluted at 1:10 mL and extract
      diluted at 1:20 mL), after artificial infestation with some 4000 larvae/animal on
      days -21, -14, -7, -1, 0, 7 and 14. The extract of D. pentaphylla was obtained by
      dehydration, spraying and extraction in absolute ethanol, at a proportion of one
      part of root powder to three parts of ethanol, this being taken as standard
      (100%). This standard extract was then diluted in water at one part of extract to
      10 and 20, for spraying on the bovines. The best result obtained (an efficiency
      rate of 76.10%) was seen 3 days after the application of the extract at a
      concentration of 1:10 mL. The extract showed no effect in inhibition of the
      laying or hatching of larvae on engorged females, these being collected from the
      bovines after treatment, and kept in the laboratory.

PMID- 16904268
TI  - Cloning and expression of mouse cytosolic alpha-mannosidase (Man2c1).
AB  - It is known that the neutral/cytosolic alpha-mannosidase (Man2c1) which can
      cleave alpha 1,2-, alpha 1,3-, and alpha 1,6-linked mannose residues, is
      stimulated by cobalt and is inhibited by furanose analogues swainsonine (SW) and
      1,4-dideoxy-1,4-imino-d-mannitol (DIM). The enzyme is involved in the degradation
      of oligomannosides derived from dolichol intermediates and the degradation of
      newly synthesized glycoproteins. An immunological relationship has been
      demonstrated between the rat endoplasmic reticulum alpha-mannosidase and the
      cytosolic alpha-mannosidase. In fact antibodies raised against the soluble alpha
      mannosidase recognized the membrane form of the ER alpha-mannosidase. A cDNA
      encoding the mouse cytosolic alpha-mannosidase was obtained by RZPD (Deutsches
      Ressourcenzentrum fur Genomforschung GmbH), Berlin, Germany. Comparison of the
      mouse genomic sequence with the cDNA sequence revealed the presence of 25 introns
      within the cytosolic alpha-mannosidase gene. The gene spans 11.5 kb from the
      major transcription initiation site to the RNA cleavage site. The transcription
      initiation site of mouse cytosolic alpha-mannosidase was mapped to 170 bases
      upstream of the ATG codon using 5' RACE. Northern blotting analysis revealed
      expression of a major transcript of 3.8 kb in all tissues examined. COS cells
      transfected with the cDNA showed a 20-fold increase in cytosolic alpha
      mannosidase activity. This enzyme activity was stimulated by cobalt and inhibited
      by DIM and EDTA. Furthermore we demonstrated that the expressed enzyme was active
      towards the radiolabeled substrate Man9GlcNAc1 giving the final product
      Man5GlcNAc1 through the formation of Man8GlcNAc1 isomer C as intermediate.

PMID- 16904269
TI  - Prostaglandin E2: a potent activator of hyaluronan synthase 1 in type-B
      synoviocytes.
AB  - We demonstrated earlier that the gene HAS1 is inactive in resting type-B
      synoviocytes but can be readily activated by a series of proinflammatory
      cytokines including IL-1beta. Here we show that in type-B-synoviocytes mRNA
      levels for the gene COX-2 increase more than 200-fold in response to IL-1beta
      treatment, whereas COX-1 mRNA levels remain virtually unchanged. We tested a
      series of eicosanoids and demonstrate that PGE(2) is a very potent activator of
      HAS1 in synoviocytes. While mumol concentrations of PGI(2) are required to
      activate HAS1, low nmol concentrations of PGE(2) are sufficient. In addition,
      while two thromboxane A(2) analogs moderately activated HAS1 at higher
      concentrations, the lipoxygenase pathway product LTB(4) was without effect. A
      series of COX inhibitors blocked IL-1beta induced HAS1 activation. Similarly,
      sodium salicylate (NaSal) also suppressed IL-1beta induced HAS1 activation.
      Furthermore, electrophoretic mobility shift assays and PGE(2) ELISA experiments
      demonstrate that NaSal completely prevents PGE(2) release but does not interfere
      with NF-kappaB translocation. PGE(2) is a very powerful activator of HAS1
      transcription and translation. Such data indicate that the effect of IL-1beta on
      HAS1 is mediated by prostaglandins. Additionally, NaSal is a potent suppressor of
      HAS1 activation. These findings point towards HAS1 as a gene of importance in
      inflammation.

PMID- 16904270
TI  - Effects of acoustic startle stimuli on interceptive action.
AB  - In reaction time (RT) tasks, presentation of a startling acoustic stimulus (SAS)
      together with a visual imperative stimulus can dramatically reduce RT while
      leaving response execution unchanged. It has been suggested that a prepared motor
      response program is triggered early by the SAS but is not otherwise affected.
      Movements aimed at intercepting moving targets are usually considered to be
      similarly governed by a prepared program. This program is triggered when visual
      stimulus information about the time to arrival of the moving target reaches a
      specific criterion. We investigated whether a SAS could also trigger such a
      movement. Human experimental participants were trained to hit moving targets with
      movements of a specific duration. This permitted an estimate of when movement
      would begin (expected onset time). Startling and sub-startle threshold acoustic
      probe stimuli were delivered unexpectedly among control trials: 65, 85, 115 and
      135 ms prior to expected onset (10:1 ratio of control to probe trials). Results
      showed that startling probe stimuli at 85 and 115 ms produced early response
      onsets but not those at 65 or 135 ms. Sub-threshold stimuli at 115 and 135 ms
      also produced early onsets. Startle probes led to an increased vigor in the
      response, but sub-threshold probes had no detectable effects. These data can be
      explained by a simple model in which preparatory, response-related activation
      builds up in the circuits responsible for generating motor commands in
      anticipation of the GO command. If early triggering by the acoustic probes is the
      mechanism underlying the findings, then the data support the hypothesis that
      rapid interceptions are governed by a motor program.

PMID- 16904271
TI  - In vitro antioxidant and antibacterial activity of Rhaphidophora pertusa stem.
AB  - Methanol extract of Rhaphidophora pertusa stem was analyzed for its antioxidant
      (DPPH, reducing power and Fe(3+) metal chelation methods) and antibacterial
      activities. The extract was found effective against the three antioxidant test
      models and exhibited strong and moderate antibacterial activity against the
      tested pathogenic bacteria.

PMID- 16904272
TI  - [Fanconi anemia: cellular and molecular features].
AB  - Fanconi anemia (FA) is a recessive human cancer prone syndrome featuring bone
      marrow failure, developmental abnormalities and hypersensitivity to DNA
      crosslinking agents exposure. 11 among 12 FA gene have been isolated. The
      biochemical functions of the FANC proteins remain poorly understood. Anyhow, to
      cope with DNA crosslinks a cell needs a functional FANC pathway. Moreover, the
      FANC proteins appear to be involved in cell protection against oxidative damage
      and in the control of TNF-alpha activity. In this review, we describe the current
      understanding of the FANC pathway and we present how it may be integrated in the
      complex networks of proteins involved in maintaining the cellular homeostasis.

PMID- 16904273
TI  - A-to-I pre-mRNA editing of the serotonin 2C receptor: comparisons among inbred
      mouse strains.
AB  - The serotonin receptor 5HT2CR pre-mRNA is subject to adenosine deamination (RNA
      editing) at five residues located within a 15 nucleotide stretch of the coding
      region. Such changes of adenosine to inosine (A-to-I) can produce 32 mRNA
      variants, encoding 24 different protein isoforms, some of which vary in
      biochemical and pharmacological properties. Because serotonin mediates diverse
      neurological processes relevant to behavior and because inbred mouse strains vary
      in their responses to tests of learning and behavior, we have examined the A-to-I
      editing patterns of the 5HT2CR mRNA in whole brains from eight mouse strains. By
      sequencing approximately 100 clones from individual mice, we generated detailed
      information on levels of editing at each site and patterns of editing that
      identify a total of 28 mRNA and 20 protein isoforms. Significant differences
      between individuals from different strains were found in total editing frequency,
      in the proportion of transcripts with 1 and 4 edited sites, in editing frequency
      at the A, B, E and D sites, in amino acid frequencies at positions 157 and 161,
      and in subsets of major protein isoforms. Primer extension assays were used to
      show that individuals within strains (six C3H.B-+rd1 and four 129SvImrJ)
      displayed no significant differences in any feature. These findings suggest that
      genetic background contributes to subtle variation in 5HT2CR mRNA editing
      patterns which may have consequences for pharmacological treatments and
      behavioral testing.

PMID- 16904274
TI  - First documented Capnocytophaga canimorsus infection in a species other than
      humans.
AB  - Capnocytophaga canimorsus was cultured from an infected, dog-inflicted bite wound
      in a pet rabbit. The wound was treated successfully and the rabbit recovered. To
      our knowledge, this is the first report of a C. canimorsus infection in a species
      other than humans.

PMID- 16904275
TI  - The effect of cryopreservation on sperm head morphometry in Florida male goat
      related to sperm freezability.
AB  - The Sperm Class Analyzer was used to investigate the effect of freeze-thawing
      procedure on Florida buck sperm head morphometry, and to relate possible changes
      in sperm head dimensions to cryopreservation success. Semen samples (n=76) were
      frozen with tris and milk-based extenders and thawed. Sperm quality samples
      (motility, morphology, acrosome), and sperm head morphometric values (length,
      width, area, perimeter, ellipticity) were compared between fresh and frozen
      thawed samples. Sperm freezability was judged according to the sperm quality
      parameters assessed. Fertility data was obtained after artificial insemination
      with cryopreserved semen. Cryopreservation success was different between freezing
      methods. Sperm head dimensions were significantly (p<0.05) smaller in
      cryopreserved tris and milk spermatozoa respectively than in those of the fresh
      samples. The sperm head morphometric parameters that had changed after
      cryopreservation were lower in suitable semen samples after thawing and with
      successful pregnancies after artificial insemination. These data suggest that
      changes in sperm head morphometry might reflect spermatozoa injury occurred
      during cryopreservation.

PMID- 16904277
TI  - Freeze-drying of nanocapsules: impact of annealing on the drying process.
AB  - Freeze-drying process was recently applied to improve the long-term storage
      stability of nanocapsules. Thermal treatment by annealing is an interesting
      process to optimize a freeze-drying cycle of these colloidal vectors. The
      objective of this paper is to investigate the impact of annealing on primary and
      secondary drying characteristics and on nanocapsules (NC) properties.
      Nanocapsules were prepared from poly-epsilon-caprolactone (PCL) biodegradable
      polymer and stabilized by polyvinyl alcohol (PVA), and then freeze-dried with two
      cryoprotectants: sucrose and poly vinyl pyrrolidone (PVP). Freeze-dried
      nanocapsules were characterized by size measurement and transmission electron
      microscopy after reconstitution. The effect of annealing on the kinetics of
      sublimation, on the mass transfer resistance and on the porosity of the freeze
      dried product has been studied in the case of PVP. Finally, the effect of
      annealing on the kinetic of secondary drying was studied and the results were
      coupled with the isotherm of sorption. Results showed that PCL nanocapsules could
      be freeze-dried without any modification of their properties in presence of the
      two cryoprotectants used. Annealing of nanocapsules suspensions could accelerate
      the sublimation rate without any modification of nanocapsules size in the case of
      the two studied cryoprotectants. Such improvement could be explained by the
      increase of ice crystals size after annealing and by the diminution of mass
      transfer resistance by the dried layer. The acceleration of sublimation rate
      seems to depend on the temperature of annealing. The annealing of sucrose
      solution slows down the secondary drying kinetic whereas no effect is observed in
      the case of PVP.

PMID- 16904278
TI  - Effects of pulse rate on thresholds and loudness of biphasic and alternating
      monophasic pulse trains in electrical hearing.
AB  - Detection thresholds and most comfortable loudnesses (MCLs) were determined as a
      function of pulse rate for standard biphasic pulse trains (BP) and for anodic and
      cathodic monophasic phases alternating at fixed intervals (ALT-m). Three
      different phase durations were examined. With a 100-micros phase duration,
      thresholds for the ALT-m stimulus were substantially (up to 12 dB) lower than for
      the BP stimuli at relatively low rates (200 pps), but were similar to the BP
      thresholds at high rates (1000 pps). Thresholds for BP pulse trains decreased
      monotonically with increasing rate, whereas the function for ALT-m waveforms was
      non-monotonic with a maximum between 400 and 1000 pps. These trends occurred for
      three different cochlear implant devices, different electrode configurations,
      and, generally, for different phase durations (10.8, 25, and 100 micros/phase).
      However, at the shorter phase durations, thresholds remained lower for the ALT-m
      stimulus, even at 5000 pps, the highest rate studied. Dynamic ranges of the BP
      pulse trains increased with increasing rate, irrespective of the phase duration
      under test, but for the ALT-m stimuli this was only true at the shorter phase
      durations tested. At a 100-mus phase duration, dynamic ranges for the ALT-m
      waveforms did not differ significantly as a function of rate. The results confirm
      previous reports that delaying charge recovery, in this case by switching from a
      BP to an ALT-m wave shape, can substantially reduce thresholds [Van Wieringen,
      A., Carlyon, R.P., Laneau, J., Wouters, J., 2005. Effects of waveform shape on
      human sensitivity to electrical stimulation of the inner ear. Hear. Res. 200, 73
      86; Carlyon, R.P., van Wieringen, A., Deeks, J.M., Long, C.J., Lyzenga, J,
      Wouters, J., 2005. Effect of inter-phase gap on the sensitivity of cochlear
      implant users to electrical stimulation. Hear. Res. 205, 210-224]. However, at
      high pulse rates, this advantage only occurs at short phase durations. In
      addition, we show that the complex interaction between the effects of pulse
      shape, rate, and phase duration on thresholds can be captured by the simple
      linear model described by Carlyon et al.

PMID- 16904279
TI  - Hyperaeration of the frontal sinus.
AB  - The nasal cavity and paranasal sinuses constitute an anatomical and functional
      unit. Paranasal sinuses communicate with the nasal cavities, which are covered by
      the same mucosa, via small openings and narrow ducts that allow both aeration and
      sinus drainage. Anatomical variations of the paranasal sinuses and nasal cavity
      are important in sinus diseases. Computerized tomography (CT) plays a critical
      role in evaluation of the patients with paranasal sinus pathology and variations.
      A 38-year-old man admitted to our clinic with headache and postnasal dripping for
      1 year. His paranasal CT scanning revealed that there is hyperaeration of the
      frontal sinus which is in continuity with the sphenoid sinus. Hyperaeration of
      the sinuses may be kept in mind in a patient complaining of headache.

PMID- 16904280
TI  - Endozoicomonas elysicola gen. nov., sp. nov., a gamma-proteobacterium isolated
      from the sea slug Elysia ornata.
AB  - A Gram-negative, strictly aerobic, rod-formed bacterium, strain MKT110(T), was
      isolated from a mollusk, the sea slug Elysia ornata collected in seawater off the
      coast of Izu-Miyake Island, Japan at a depth of 15m. Comparative 16S rRNA gene
      sequences analysis indicated that the isolate MKT110(T) constituted a novel
      lineage in gamma-proteobacteria related to the genera Zooshikella,
      Oceanospirillum, Microbulbifer, Marinobacter, Saccharospirillum and Pseudomonas.
      The strain MKT110(T) was closely related to the clones from marine sponge
      Halichondria okadai (AB054136, AB054161) and the coral Pocillopora damicornis
      (AY700600, AY700601). The phylogenetic tree based on the 16S rRNA gene sequences
      showed that MKT110(T) and four clones formed a sub-lineage related to the genus
      Zooshikella, with a bootstrap value of 100%. MKT110(T) required salt for its
      growth and was mesophilic. The bacterium contained 16:1omega7c, 16:0 and 14:0 as
      major cellular fatty acids, and 3-OH 14:0, 3-OH 10:0 and 3-OH 12:0 as major
      hydroxy fatty acids. The DNA base composition of the isolate was 50.4 mol% G+C.
      The major quinone was Q-9. The bacterium is distinguished from currently
      recognized bacterial genera based on phylogenetic and phenotypic features and
      should be classified in a novel genus for which the name Endozoicomonas elysicola
      gen. nov., sp. nov. is proposed. (type strain MKT110(T)=IAM 15107(T)=KCTC
      12372(T); GenBank accession no. AB196667).

PMID- 16904281
TI  - Comparison of the recovery spread in analytical development and routine quality
      control--based on the ICH quality guideline Q2B.
AB  - In the present study, a simulation was performed for the ICH Q2B guideline for
      assessing the accuracy. By means of an experimental data set a permutation has
      been performed to investigate in which interval experimental mean recovery can be
      expected to scatter just by random effects. A good agreement has been found
      between the experimental intervals obtained by means of a permutation and the
      statistically derived confidence intervals. These findings could be confirmed
      with additionally generated virtual data sets with a true mean of 100% and a true
      standard deviation of 0.7%.

PMID- 16904282
TI  - Determination of curcumin by its quenching effect on the fluorescence of Eu3+
      tryptophan complex.
AB  - Curcumin (C21H20O6, CU) is a natural antioxidant, which is considered to be a
      very useful compound in health matters, and is employed in the treatment of
      cardiovascular and arthritic illnesses. It is found that the fluorescence
      intensity of Eu3+-tryptophan (Trp) can be greatly quenched by curcumin in the
      buffer of pH 7.7. Under optimum conditions, the quenched intensity of
      fluorescence is in proportion to the concentration of curcumin in the range of
      1.0x10(-8) to 1.2x10(-4) mol L(-1). The detection limit (S/N=3) is 9.0x10(-10)
      mol L(-1). The synthetic and actual samples are satisfactorily determined. In
      addition, the interaction mechanism is also investigated.

PMID- 16904283
TI  - Impact of Maillard type glycation on properties of beta-lactoglobulin.
AB  - The Maillard reaction occurs during many thermal treatments of foods. It is used
      because of its role in creating colors, flavors, textures and other functional
      properties in foods. Glycated beta-lactoglobulin (BLG) can improve techno
      functional properties as heat stability, emulsifying and foaming properties.
      Among the six common sugars used, arabinose and ribose induce the highest degree
      of modification of proteins. Glycation induced also the oligomerization of BLG
      monomers. Depending on the reactivity of the sugar, the population of oligomers
      produced showed smaller or larger heterogeneity in molecular masses. Antiradical
      properties of glycated BLG were estimated using a radical scavenging activity
      test. Glycation induced a radical scavenging activity; the intensity depended on
      the sugar used for modification.

PMID- 16904284
TI  - An epitope shared by cellular cytokeratin and Orientia tsutsugamushi.
AB  - Many microbial pathogens have epitopes shared with host cell components and these
      epitopes may induce transient or longer-term tissue-damaging autoantibody
      responses. We observed that several mouse monoclonal antibodies (MAbs) raised
      against Orientia tsutsugamushi were also reactive with host cells. One such
      antibody, MAb Rb105, cross-reacted with the cytoskeleton, as shown by
      immunofluorescent staining. Biochemical studies identified the cross-reacting
      component as a cytokeratin protein. These results identify an epitope shared by
      O. tsutsugamushi and the cytokeratins of host cells. In addition, antibodies
      cross-reactive with the cytoskeleton were detected in the sera of scrub typhus
      patients, suggesting that an epitope similar to that detected by MAb Rb105 may be
      recognized by human antibodies.

PMID- 16904285
TI  - Absorption of the nerve agent VX (O-ethyl-S-[2(di-isopropylamino)ethyl] methyl
      phosphonothioate) through pig, human and guinea pig skin in vitro.
AB  - The physico-chemical properties of VX make the skin the most likely route of
      absorption into the human body. The development of effective medical
      countermeasures against such percutaneous threat agents relies on the use of
      appropriate animal models, as the inherent toxicity of nerve agents precludes the
      use of human volunteers. Previous studies have characterised the mechanism of
      nerve agent toxicity in rodent models, however, it is generally accepted that one
      of the most appropriate animal models for human skin absorption is the domestic
      pig. The purpose of the present study was to measure and compare the skin
      absorption kinetics of VX in vitro using pig, human and guinea pig skin to
      highlight any potential species differences in skin permeability. When undiluted
      VX was applied directly to the skin, the permeability of guinea pig skin was
      approximately 7-fold greater than human skin. There was no significant difference
      in the permeability of pig and human skin. When VX diluted with isopropyl alcohol
      was applied to the skin, the permeability of guinea pig skin was approximately 4
      fold greater than human skin. There was no significant difference in the
      permeability of pig and human skin. From this data it may be inferred that
      dermatomed, abdominal pig skin is an appropriate model for the human skin
      absorption of VX.

PMID- 16904286
TI  - Conflicting phylogenetic position of Schizosaccharomyces pombe.
AB  - The phylogenetic position of the fission yeast Schizosaccharomyces pombe in the
      fungal Tree of Life is still controversial. Three alternative phylogenetic
      positions have been proposed in the literature, namely (1) a position basal to
      the Hemiascomycetes and Euascomycetes, (2) a position as a sister group to the
      Euascomycetes with the Hemiascomycetes as a basal branch, or (3) a sister group
      to the Hemiascomycetes with Euascomycetes as a basal branch. Here we compared 91
      clusters of orthologous proteins containing a single orthologue that are shared
      by 19 eukaryote genomes. The major part of these 91 orthologues supports a
      phylogenetic position of S. pombe as a basal lineage among the Ascomycota, thus
      supporting the second proposition. Interestingly, part of the orthologous
      proteins supported a fourth, not yet described alternative, in which S. pombe is
      basal to both Basidiomycota and Ascomycota. Both topologies of phylogenetic trees
      are well supported. We believe that both reflect correctly the phylogenetic
      history of the species concerned. This apparent paradox may point to a
      heterogeneous nuclear genome of the fungi. Importantly, this needs to be taken in
      consideration for a correct understanding of the fungal Tree of Life.

PMID- 16904287
TI  - Neurocognitive consequences of cigarette smoking in young adults--a comparison
      with pre-drug performance.
AB  - The present study examined effects of current and past regular cigarette smoking
      in young adult subjects. One hundred and twelve 17-21-year-old subjects, assessed
      since infancy, were evaluated using a battery of neurocognitive tests for which
      commensurate measures were obtained at 9-12 years of age, prior to the initiation
      of regular smoking. Smokers, determined by urinalysis and self-report, were
      categorized as heavy (>9 cigarettes per day) and light (<9 cigarettes per day)
      current smokers and former smokers, the latter having smoked cigarettes regularly
      in the past but not for at least 6 months. A third of the subjects were currently
      smoking cigarettes regularly with half of these being heavy smokers. Among former
      smokers, the average duration of smoking was slightly less than 2 years. Overall
      IQ, memory, processing speed, vocabulary, attention and abstract reasoning were
      the primary outcomes with comparisons being made between each of the three user
      groups and a control group who never smoked regularly. After accounting for
      potentially confounding factors including clinical assessment, marihuana use and
      pre-drug performance in the relevant cognitive domain, current regular smokers
      did significantly worse than non-smokers in a variety of cognitive areas
      predicated upon verbal/auditory competence including receptive and expressive
      vocabulary, oral arithmetic, and auditory memory. This impact of current smoking
      appears to behave in a dose-response and duration-related fashion. In contrast,
      former smokers differed from the non-smokers only in the arithmetic task. These
      results suggest that regular smoking during early adulthood is associated with
      cognitive impairments in selected domains and that these deficits may be reversed
      upon cessation. Together, the findings add to the body of evidence to be used in
      persuading adolescents and young adults against the initiation of smoking and, if
      currently smoking, the advantages of stopping.

PMID- 16904288
TI  - Stochastic complexities of general mixture models in variational Bayesian
      learning.
AB  - In this paper, we focus on variational Bayesian learning of general mixture
      models. Variational Bayesian learning was proposed as an approximation of
      Bayesian learning. While it has provided computational tractability and good
      generalization in many applications, little has been done to investigate its
      theoretical properties. The asymptotic form was obtained for the stochastic
      complexity, or the free energy in the variational Bayesian learning of a mixture
      of exponential-family distributions, which is the main contribution this paper
      makes. We reveal that the stochastic complexities become smaller than those of
      regular statistical models, which implies that the advantages of Bayesian
      learning are still retained in variational Bayesian learning. Moreover, the
      derived bounds indicate what influence the hyperparameters have on the learning
      process, and the accuracy of the variational Bayesian approach as an
      approximation of true Bayesian learning.

PMID- 16904290
TI  - Developmental outcome in benign myoclonic epilepsy in infancy and reflex
      myoclonic epilepsy in infancy: a literature review and six new cases.
AB  - Benign myoclonic epilepsy in infancy is a rare syndrome with just over 100 cases
      reported since the first syndromic description by Dravet and Bureau [Dravet, C.,
      Bureau, M., 1981. The benign myoclonic epilepsy of infancy. Rev.
      Elecroencephalogr. Neurophysiol. Clin. 11, 438-444]. This includes 23 infants
      with reflex myoclonic epilepsy whose inclusion in the wider syndrome remains
      debatable. We have reviewed the literature and present data from six further
      cases. Prognosis in respect of long term seizure freedom is good with sodium
      valproate being the most effective medication. However, the cognitive outcome is
      much less certain with cognitive problems present in one-third of children who
      have long term follow up. The cognitive outcome in reflex myoclonic epilepsy of
      infancy is normal in all reported cases. The term benign may be appropriately
      used to describe the myoclonic seizures but must be used cautiously when
      counselling families about cognitive outcome. The clinical heterogeneity within
      this syndrome suggests that there may be a variety of genetic mechanisms that
      underlie the presentation. Clinicians should distinguish the syndrome of reflex
      myoclonic epilepsy in infancy from benign myoclonic epilepsy of infancy and all
      patients should continue developmental follow up for several years after
      diagnosis.

PMID- 16904289
TI  - MAGI-3 regulates LPA-induced activation of Erk and RhoA.
AB  - Lysophosphatidic acids (LPA) exert multiple biological effects through specific G
      protein-coupled receptors. The LPA-activated receptor subtype LPA(2) contains a
      carboxyl-terminal motif that allows interaction with PDZ domain-containing
      proteins, such as NHERF2 and PDZ-RhoGEF. To identify additional interacting
      partners of LPA(2), the LPA(2) carboxyl-terminus was used to screen a proteomic
      array of PDZ domains. In addition to the previously identified NHERF2, several
      additional LPA(2)-interacting PDZ domains were found. These included MAGI-2, MAGI
      3 and neurabin. In the present work, we demonstrate the specific interaction
      between LPA(2) and MAGI-3, and the effects of MAGI-3 in colon cancer cells using
      SW480 as a cell model. MAGI-3 specifically bound to LPA(2), but not to LPA(1) and
      LPA(3). This interaction was mediated via the fifth PDZ domain of MAGI-3
      interacting with the carboxyl-terminal 4 amino acids of LPA(2), and mutational
      alteration of the carboxyl-terminal sequences of LPA(2) severely attenuated its
      ability to bind MAGI-3. LPA(2) also associated with MAGI-3 in cells as determined
      by co-affinity purification. Overexpression of MAGI-3 in SW480 cells showed no
      apparent effect on LPA-induced activation of Erk and Akt. In contrast, silencing
      of MAGI-3 expression by siRNA drastically inhibited LPA-induced Erk activation,
      suggesting that the lack of an effect by overexpression was due to the high
      endogenous MAGI-3 level in these cells. Previous studies have shown that the
      cellular signaling elicited by LPA results in activation of the small GTPase RhoA
      by Galpha(12/13) - as well as Galpha(q)-dependent pathways. Overexpression of
      MAGI-3 stimulated LPA-induced RhoA activation, whereas silencing of MAGI-3 by
      siRNA resulted in a small but statistically significant decrease in RhoA
      activation. These results demonstrate that MAGI-3 interacts directly with LPA(2)
      and regulates the ability of LPA(2) to activate Erk and RhoA.

PMID- 16904292
TI  - Premorbid IQ as a predictor for the course of IQ in first onset patients with
      schizophrenia: a 10-year follow-up study.
AB  - The aim of the present study was to examine the longitudinal course of IQ and its
      heterogeneity in patients with schizophrenia, from the perspective of the two
      main "subtypes" of schizophrenia described in the literature: progressive
      cognitive deficit versus cognitive stabilisation or recovery. Premorbid IQ scores
      and WAIS IQ scores of 100 first onset patients were obtained at first
      hospitalization (T1) and after 10 years (T2). Significant changes in IQ over time
      were found, representing (i) at T1, a deterioration compared to premorbid
      intelligence (B=-6.3, 95% CI -9.5 to -3.0, p<0.0001), followed by (ii) a recovery
      at T2 where IQ matched premorbid intelligence again (B=0.5, 95% CI -3.1 to 4.0,
      p=0.79). In addition, a significant interaction was found between course of IQ
      over time and estimated premorbid IQ, demonstrating that subjects with lower
      premorbid IQ levels remained stable over time whereas in individuals with higher
      premorbid IQ levels a pattern of deterioration was evident at T1, followed by a
      recovery up to premorbid level at T2. The data confirm the importance of
      estimated premorbid IQ as an indicator of the longitudinal course of cognitive
      functioning in patients with schizophrenia and add evidence to the hypothesis of
      heterogeneity or "subtypes" of schizophrenia. The data, however, do not confirm
      the existence of progressive deterioration of cognitive functioning. Rather,
      catching up of cognitive function later in the course of the illness may take
      place in those whose deficits become apparent in the early phases of illness,
      whereas those with the most severe premorbid impairments remain stable.

PMID- 16904291
TI  - No association between the metabotropic glutamate receptor type 3 gene (GRM3) and
      schizophrenia in a Japanese population.
AB  - Several lines of evidence have suggested that the metabotropic glutamate receptor
      3 (GRM3) gene is a candidate susceptibility gene for schizophrenia. To our
      knowledge, six studies have investigated the genetic association between GRM3 and
      schizophrenia, although the results have been quite controversial. In the present
      study, we investigated the association between the GRM3 gene and schizophrenia in
      402 Japanese people by analyzing 10 single nucleotide polymorphisms (SNPs),
      including all SNPs that showed significant results in previous studies. We
      observed no significant difference in allelic frequencies or genotypic
      distributions of the 10 SNPs between the controls and patients. A permutation
      test showed no significant global differences in estimated haplotype frequencies
      between the controls and patients. Thus, the present study provides no positive
      evidence of an association between the GRM3 gene and schizophrenia in the
      Japanese population.

PMID- 16904293
TI  - Molecular investigation of an outbreak of multidrug-resistant Acinetobacter
      baumannii, with characterisation of class 1 integrons.
AB  - We investigated a multidrug-resistant Acinetobacter baumannii outbreak in the
      Intensive Care Unit (ICU) of a tertiary care hospital in Greece over a 3-month
      period. Molecular typing of the outbreak isolates from 31 patients revealed that
      two distinct genotypes were involved. Nine isolates, belonging to both genotypes,
      were resistant to carbapenems. Samples from the ICU environment and from the
      hands of personnel were collected to identify possible contamination. Class 1
      integrons of 3.1, 2.5 and 2.2 kb were amplified from the clinical and
      environmental isolates. The 3.1 kb integron carrying five gene cassettes was
      found for the first time in A. baumannii. The outbreak ceased after
      implementation of hygienic measures in the ICU, including complete cleaning and
      disinfection.

PMID- 16904294
TI  - Call for the international adoption of microbiological breakpoints for
      fluoroquinolones and Streptococcus pneumoniae.
AB  - The use of current Clinical and Laboratory Standards Institute levofloxacin
      breakpoints for assessing fluoroquinolone resistance in Streptococcus pneumoniae
      is inadequate for detecting isolates possessing first-step parC mutations.
      Consequently, the risk for development of fluoroquinolone resistance is greatly
      underestimated. Adopting microbiological breakpoints for fluoroquinolones and S.
      pneumoniae, where parC mutations are rare in susceptible isolates, more
      accurately describes the emergence of resistance and may help to prevent a number
      of future fluoroquinolone treatment failures. Additionally, we propose that the
      use of a second fluoroquinolone marker, such as ciprofloxacin, offers the best
      prediction for detecting an isolate possessing a first-step parC mutation.

PMID- 16904295
TI  - In vitro susceptibilities of aerobic and facultative Gram-negative bacilli
      isolated from patients with intra-abdominal infections in the Asia-Pacific
      region: 2004 results from SMART (Study for Monitoring Antimicrobial Resistance
      Trends).
AB  - In the 2004 Study for Monitoring Antimicrobial Resistance Trends (SMART), 14
      centres from six countries in Asia-Pacific collected 1198 unique aerobic and
      facultative Gram-negative bacilli from intra-abdominal infections for
      susceptibility testing to 12 antimicrobial agents. Enterobacteriaceae comprised
      82% of the total isolates. Escherichia coli was the most commonly isolated
      species (43%). Resistance rates were generally higher in Enterobacteriaceae
      isolated from Asian centres than those isolated from Oceania centres. There was
      little difference in susceptibility rates between community- and hospital
      acquired Enterobacteriaceae for carbapenems. Extended-spectrum beta-lactamase
      (ESBL)-producers typically had a more resistant profile than non-ESBL-producers,
      but were usually susceptible to carbapenems. Of the antimicrobial agents tested,
      carbapenems were the most reliably active in vitro against Enterobacteriaceae
      recovered from patients in Asia-Pacific with intra-abdominal infections.

PMID- 16904296
TI  - Respiratory tract infections: at-risk patients, who are they? Implications for
      their management with levofloxacin.
AB  - At this symposium, the bacterial aetiologies of community-acquired pneumonia and
      acute exacerbations of chronic bronchitis were evaluated. By reviewing the
      clinical criteria for the identification of at-risk patients and the
      recommendations for antimicrobial drug selection in treatment guidelines, the
      role of levofloxacin in clinical practice was explored. In addition,
      consideration was also given to the economic impact of using levofloxacin in at
      risk patients.

PMID- 16904297
TI  - Comparative elution of moxifloxacin from Norian skeletal repair system and
      acrylic bone cement: an in vitro study.
AB  - The objective of this study was to evaluate the efficacy of Norian skeletal
      repair system (SRS), a novel biodegradable and injectable form of calcium
      phosphate cement with a composition similar to that of cancellous bone, as a
      carrier for moxifloxacin, which is the most potent quinolone agent against
      staphylococci and Enterobacteriaceae. Norian SRS was mixed with moxifloxacin at a
      ratio of ca. 100:3 at room temperature and solidified in the bottom of a
      cylindrical vial. The same procedure was followed for acrylic bone cement. A
      total of five vials were prepared per system. Mueller-Hinton broth was placed
      over the free surface of both systems and the vials were transferred to a 37
      degrees C incubator. The broth was replaced daily until visual degradation of
      both systems. Moxifloxacin was measured in aliquots of broth after passage
      through a high-performance liquid chromatography system. Optical degradation of
      both systems occurred after 450 days. Until Day 17, concentrations eluted from
      both systems were similar. After Day 18 until degradation, concentrations eluted
      by Norian SRS were statistically higher than those eluted by acrylic bone cement
      and ranged between 100 mg/L and 800 mg/L. The mean area under the concentration
      time curve (AUC) over 450 days of sampling was 241 935.0 mg/L day for Norian SRS
      and 18 300.0 mg/L day for the acrylic bone cement system (P=0.043). Norian SRS is
      a novel biodegradable system providing excellent strength and mineralisation to
      bone. It was shown that this system allows in vitro elution of moxifloxacin at
      significant concentrations, making it a promising candidate for the therapy of
      chronic osteomyelitis.

PMID- 16904298
TI  - Antipsychotic augmentation of serotonergic antidepressants in treatment-resistant
      obsessive-compulsive disorder: a meta-analysis of the randomized controlled
      trials.
AB  - This study aimed to determine the effectiveness of antipsychotic augmentation of
      serotonergic antidepressants in the management of treatment-resistant obsessive
      compulsive disorder by carrying out a meta-analysis of all randomized controlled
      trials. Studies selected through a literature search conducted in March 2006. Ten
      trials comparing antipsychotic drugs versus placebo met inclusion criteria
      (haloperidol [n=1], risperidone [n=3], olanzapine [n=2], quetiapine [n=4]). A
      total of 157 patients were randomized to study drug and 148 were randomized to
      placebo. Response occurred more often among patients randomized to antipsychotic
      drugs. The weighted combined response rate ratio by random effects meta-analysis
      was 3.31 (95% CI 1.40-7.84). Significant between studies heterogeneity was partly
      explained by the definition of refractoriness, the type and dose of the drug used
      and the inclusion or exclusion of patients with tic disorders. The study supports
      the use of antipsychotic drugs as an augmentation strategy but more and larger
      trials are needed.

PMID- 16904299
TI  - Electroconvulsive stimuli selectively affect behavior and neuropeptide Y (NPY)
      and NPY Y(1) receptor gene expressions in hippocampus and hypothalamus of
      Flinders Sensitive Line rat model of depression.
AB  - Previously we reported that basal neuropeptide Y (NPY)-like immunoreactivity-(LI)
      in hippocampus of the "depressed" Flinders Sensitive Line (FSL) rats was lower
      compared to the control Flinders Resistant Line (FRL) and that electroconvulsive
      stimuli (ECS) raise NPY-LI in discrete brain regions. Here we studied NPY mRNA
      expression, NPY Y(1) receptor (Y(1)) mRNA expression and binding sites, and
      behavior under basal conditions (Sham) and after repeated ECS. Baseline NPY and
      Y(1) mRNAs in the CA1-2 regions and dentate gyrus were lower while the Y(1)
      binding was higher in the FSL. ECS had larger effects on both NPY and behavior in
      the FSL rats. ECS increased NPY mRNA in the CA1-2, dentate gyrus and hypothalamus
      in FSL, but only in the dentate gyrus in FRL. ECS also increased Y(1) mRNA in the
      CA1-2, dentate gyrus and the parietal cortex in both strains, while in the
      hypothalamus the increase was observed only in the FSL rats. Consistently with
      Y(1) mRNA increase, Y(1) binding was downregulated in the corresponding regions.
      ECS decreased FSL immobility in the Porsolt swim test. These findings suggest
      that NPY is involved in depressive disorder and that antidepressant effects of
      ECS may in part be mediated through NPY.

PMID- 16904300
TI  - The Drosophila ramshackle gene encodes a chromatin-associated protein required
      for cell morphology in the developing eye.
AB  - We have identified ramshackle (ram) as a dominant suppressor of hedgehog loss-of
      function in the developing Drosophila eye. We have characterized the gene and it
      encodes a double bromodomain protein with eight WD40 repeats. The Ram protein is
      localized predominantly to polytene chromosome interbands and is required for the
      transcription of some genes. ram is an essential gene and null mutants die during
      larval life. In the developing retina, ram mutant cells have morphological
      defects including disrupted apical junctions, disorganized actin cytoskeletons
      and mislocalized nuclei, which are followed by delays in cell-cycle transitions
      and the expression of differentiation markers. ram is a conserved gene: its
      vertebrate homolog (WDR9), which lies in Down's Syndrome Critical region 2 (DCR2)
      is also known to be associated with Brahma-Related-Gene 1 (BRG1).

PMID- 16904301
TI  - Doxorubicin encapsulation and diffusional release from stable, polymeric,
      hydrogel nanoparticles.
AB  - We have recently described the preparation of stable, polymeric nanoparticles,
      composed of poly(ethylene glycol) and poloxamer 407 (Pluronic F127), prepared via
      inverse emulsion photopolymerization. In the present study we report on the
      performance of this novel colloidal system as a controlled delivery system for
      small hydrophobic drugs. Successful encapsulation of doxorubicin occurred through
      hydrophobic interactions, taking advantage of particle nanoarchitecture. Loadings
      of up to 8.7wt.% were achieved with a reproducible, fast, solvent evaporation
      procedure. In vitro drug release, monitored by fluorescence spectrometry and
      HPLC, revealed a minor burst (approximately 10% at 37 degrees C) and sustained,
      diffusional release for over 1 week; furthermore, drug encapsulation
      significantly delayed doxorubicin degradation kinetics.

PMID- 16904302
TI  - Comparative trial of different anti-bacterial combinations with propolis and
      ciprofloxacin on Pseudomonas keratitis in rabbits.
AB  - The aim of the current study was to evaluate the effects of five different
      treatment combinations to find out whether propolis could be an alternative or an
      adjunctive treatment, in experimental Pseudomonas aeruginosa keratitis.
      Intrastromal P. aeruginosa strains were given to both eyes of 20 young New
      Zealand white rabbits. The rabbits were randomly divided equally into five
      treatment groups; ciprofloxacin and dexamethasone drops (C+D), ciprofloxacin drop
      (C), ciprofloxacin and propolis drops (C+P), propolis drop (P), 3% ethanol drop
      (control), respectively. Directly before the first treatment and 108 h after
      inoculation, the eyes were examined by slit lamp to assess the corneal opacity
      and rabbits were sacrificed for bacterial count. The mean corneal opacity scores
      and the mean bacterial counts log cfu/ml were significantly different in the
      treatment groups (P=0.001; ANOVA). According to post hoc tests for both the mean
      bacterial counts and corneal opacity scores, C+D, C, C+P groups were found to be
      statistically the same (P>0.05), and although the P group had significantly
      better scores than the control group it did not reach the scores of the rest of
      the treatment groups (P<0.01). We conclude that propolis may be a useful
      adjunctive agent but should not be regarded as a replacement for traditional
      antibiotic therapy for P. aeruginosa keratitis in rabbits.

PMID- 16904303
TI  - Chitinases produced by Paenibacillus illinoisensis and Bacillus thuringiensis
      subsp. pakistani degrade Nod factor from Bradyrhizobium japonicum.
AB  - Chitinases are enzymes that hydrolyze internal beta-1,4-N-acetyl-D-glucosamine
      linkages of chitin. Since the backbone of Nod factors is a chitin oligomer, we
      investigated whether chitinases produced by soil bacteria Paenibacillus
      illinoisensis KJA-424 and Bacillus thuringiensis subsp. Pakistani HD 395 are able
      to degrade Nod factor produced by Bradyrhizobium japonicum, a phenomenon that
      could disrupt B. japonicum-soybean signaling and nodule establishment when
      chitinases are present. Purified Nod factor [LCO Nod Bj-V (C(18:1), MeFuc)] was
      isolated from Bradyrhizobium japonicum and incubated with crude chitinases
      isolated from KJA-424 and HD395, with or without acetate buffer. After 15 h of
      incubation, Nod factor in the resulting solution was quantified by HPLC.
      Degradation was greatest following treatment with KJA-424 (91.9%) and HD395
      (86.5%) chitinases in acetate buffer. Treatments that included acetate buffer had
      higher levels of degradation than those without. For all treatments degradation
      was greater than 77%.

PMID- 16904305
TI  - Endocytic recycling pathways: emerging regulators of cell migration.
AB  - The past five years have seen a steady accumulation of data reinforcing the view
      that Rab-regulated recycling pathways contribute to cell migration. In
      particular, detailed descriptions have emerged of the mechanisms that recruit
      integrins and growth factor receptors to Rab4- and Rab11-driven pathways. Recent
      work provides new insight into the importance of particular recycling events in
      cell migration within a variety of physiological contexts.

PMID- 16904306
TI  - Pathophysiology of leukocyte-tissue interactions.
AB  - Unlike most somatic cells, leukocytes are constitutively non-adherent. However,
      adhesive interactions are not only a required step in essentially all effector
      functions performed by leukocytes, but they also relay increasingly well-defined
      intracellular signals that affect the leukocyte as well as the surrounding
      tissues. Dissecting such signals in leukocytes has provided a wealth of
      information that contributes to our understanding of how adhesion controls higher
      order biological responses, ranging from cell migration to proliferation,
      differentiation and survival.

PMID- 16904307
TI  - ArfGAP family proteins in cell adhesion, migration and tumor invasion.
AB  - The identification of several ArfGAP proteins as binding partners of paxillin, an
      integrin signaling and scaffolding protein, has suggested the existence of
      molecular links between integrin functions and intracellular traffic, as proposed
      by MS Bretscher long ago. Among the paxillin-binding ArfGAPs, AMAP1 has recently
      been strongly implicated in tumor invasion as well as malignancy, owing to its
      highly augmented expression in tumors and its direct involvement in invasive
      activities. Another ArfGAP, Git2, was found to be a component of the Gbetagamma
      mediated directional sensing machinery, while simultaneously playing an essential
      role in the suppressive control of superoxide production, which is mediated by
      vesicle transport in GPCR-stimulated neutrophils. These emerging molecular
      mechanisms may further delineate key processes regulating intracellular traffic
      as principal controls of cell motility and invasive activities.

PMID- 16904308
TI  - Recovery and recycling practices in municipal solid waste management in Lagos,
      Nigeria.
AB  - The population of Lagos, the largest city in Nigeria, increased seven times from
      1950 to 1980 with a current population of over 10 million inhabitants. The
      majority of the city's residents are poor. The residents make a heavy demand on
      resources and, at the same time, generate large quantities of solid waste.
      Approximately 4 million tonnes of municipal solid waste (MSW) is generated
      annually in the city, including approximately 0.5 million of untreated industrial
      waste. This is approximately 1.1 kg/cap/day. Efforts by the various waste
      management agencies set up by the state government to keep its streets and
      neighborhoods clean have achieved only minimal success. This is because more than
      half of these wastes are left uncollected from the streets and the various
      locations due to the inadequacy and inefficiency of the waste management system.
      Whilst the benefits of proper solid waste management (SWM), such as increased
      revenues for municipal bodies, higher productivity rate, improved sanitation
      standards and better health conditions, cannot be overemphasized, it is important
      that there is a reduction in the quantity of recoverable materials in residential
      and commercial waste streams to minimize the problem of MSW disposal. This paper
      examines the status of recovery and recycling in current waste management
      practice in Lagos, Nigeria. Existing recovery and recycling patterns, recovery
      and recycling technologies, approaches to materials recycling, and the types of
      materials recovered from MSW are reviewed. Based on these, strategies for
      improving recovery and recycling practices in the management of MSW in Lagos,
      Nigeria are suggested.

PMID- 16904309
TI  - Chemiluminescent optical fiber immunosensor for detection of autoantibodies to
      ovarian and breast cancer-associated antigens.
AB  - We report herein the development of an optical fiber based chemiluminescent
      immunosensor for detection of the native autoimmune response to GIPC-1, a PDZ
      containing protein involved in regulation of G-protein signaling. The recombinant
      protein GIPC-1 was expressed in bacteria, purified, refolded and conjugated to
      the tip of an optical fiber. A human monoclonal 27.B1 IgM isolated from a breast
      cancer patient, which targets the GIPC-1 protein, was used for calibration of the
      immunosensor and was detected down to a concentration of 30 pg/ml. We determined
      that the fiber-optic immunosensor had a detection limit 50 times lower than
      chemiluminescent ELISA, and approximately 500 times lower than colorimetric
      ELISA. In addition, sera from 11 ovarian cancer patients, 22 breast cancer
      patients and asymptomatic controls were tested for the presence of IgM anti-GIPC
      1 autoantibodies in their serum using the two methods. The immunosensor assay
      detected 54% and 77% GIPC-1 positive sera within ovarian and breast cancer
      patients, respectively, as compared to chemiluminescent ELISA, which only
      detected 18% and 27%, respectively. We envision that this immunosensor may serve
      as a diagnostic tool for screening women for ovarian and breast cancer at an
      early stage, thus increasing their chance of survival.

PMID- 16904310
TI  - Transcriptional control thrown for a loop.
AB  - The relationships among in vivo chromatin structures, chromosome organization and
      genome function must be understood in order to reveal the hidden regulatory
      information in our genomes. Rather than being stable architectural features, it
      appears that chromatin and chromosome conformations at all levels are highly
      dynamic, which is the key to their function. Studies in recent years have
      elucidated long-range interactions or folded chromatin conformations that play
      significant roles in gene regulation. Most recently, intrachromosomal
      associations and co-associations with shared nuclear transcription compartments
      have been discovered in mammals, with the potential to greatly expand our view of
      how the genome is regulated.

PMID- 16904311
TI  - Patients and health professionals working together to improve clinical research:
      where are we going?
AB  - The pace of active involvement of patients in clinical research has increased
      over the last 10-15 years. Advocacy for this engagement between patients and
      health professionals is briefly traced, based on the author's experiences both as
      an independent advocate and as co-founder and chairman (1995-1999) of the
      Consumers' Advisory Group for Clinical Trials (CAG-CT). A brief history is
      outlined. As the benefits and minor drawbacks of collaborative working have
      become increasingly evident, attitudes have changed and methodologies have
      developed. A new professionalism in relationships with doctors is being sought:
      common vocabularies need to be defined. Some research governance problems are
      identified: forward thinking to solve them is advocated.

PMID- 16904312
TI  - Immediate nephrectomy versus preoperative chemotherapy in the management of non
      metastatic Wilms' tumour: results of a randomised trial (UKW3) by the UK
      Children's Cancer Study Group.
AB  - PURPOSE: To determine if patients receiving preoperative chemotherapy with
      vincristine and actinomycin D for non-metastatic Wilms' tumour have a more
      advantageous stage distribution and so need less treatment compared to patients
      who have immediate nephrectomy, without adversely affecting outcome. METHODS:
      Between 1991 and 2001, a total of 205 patients with newly diagnosed non
      metastatic renal tumours, of which 186 had Wilms' histologies, were randomly
      assigned either to immediate surgery or to 6 weeks preoperative chemotherapy and
      then delayed surgery. Both groups of children received postoperative chemotherapy
      according to tumour stage and histology determined at the time of nephrectomy.
      RESULTS: There was a significant improvement in the stage distribution for
      patients with Wilms' histologies receiving delayed surgery compared to those
      having immediate nephrectomy (stage I: 65.2% versus 54.3%; stage II: 23.9% versus
      14.9%; stage III: 9.8% versus 29.8%, chi2 test for trend=7.02, p=0.008). This
      improvement resulted in 20% fewer children receiving radiotherapy or doxorubicin
      yet event-free and overall survivals at 5 years of 79.6% and 89.0%, respectively,
      were similar in the two groups. CONCLUSION: Six weeks of preoperative
      chemotherapy with vincristine and actinomycin D results in a significant shift
      towards a more advantageous stage distribution and hence reduction in therapy,
      while maintaining excellent event free and overall survival in children with non
      metastatic Wilms' tumour. Around 20% of survivors were therefore spared the late
      effects of doxorubicin or radiotherapy. Our results suggest that all children
      with non-metastatic Wilms' tumour should receive chemotherapy prior to tumour
      resection.

PMID- 16904313
TI  - Breast cancer: multidisciplinary care and clinical outcomes.
AB  - A multidisciplinary approach to the management of breast cancer is the standard
      of care in developed health systems. We performed a systematic review to assess
      the extent and quality of evidence on whether multidisciplinary care (MDC), or
      related aspects of care contribute to clinical outcomes in breast cancer, and in
      particular whether these influence survival. Only two primary studies have looked
      at MDC and neither of these studies considered long-term outcomes. The studies of
      MDC (case series) provide weak evidence that MDC may alter treatment patterns.
      Several population-based cohort studies showed that related aspects of team work,
      specialist (surgeon) and hospital workload and specialisation, are associated
      with improved survival. This group of studies used better quality design with
      more clearly defined outcome measures, and most of the studies have allowed for
      possible confounding variables. Evidence of a survival benefit was most
      consistent for specialist (surgeon) effect. However, the reasons behind the
      improved survival reported in these studies are unclear, and it is unlikely that
      this is entirely attributable to treatment patterns. We conclude that although
      intrinsically multidisciplinary care should be associated with better survival,
      there remains a paucity of evidence to support this. Studies of the long-term
      clinical effects of MDC in breast cancer should be a priority for future
      evaluation.

PMID- 16904314
TI  - Does sunlight prevent cancer? A systematic review.
AB  - Accumulating evidence for beneficial effects of sunlight on several types of
      cancer with a high mortality rate makes it necessary to reconsider the health
      recommendations on sun exposure, which are now mainly based on the increased
      risks for skin cancer. We reviewed all published studies concerning sun exposure
      and cancer, excluding skin cancer. All selected studies on prostate (3 ecologic,
      3 case-control and 2 cohort), breast (4 ecologic, 1 case-control and 2 cohort)
      and ovary cancer (2 ecologic and 1 case-control) showed a significantly inverse
      correlation between sunlight and mortality or incidence. Two ecologic, 1 case
      control and 2 prospective studies showed an inverse relation between sunlight and
      colon cancer mortality; 1 case-control study found no such association. Ecologic
      studies on non-Hodgkin lymphoma (NHL) mortality and sunlight gave conflicting
      results: early studies showing mostly positive and later studies showing mostly
      negative correlations. Three case-control studies and 1 cohort study found a
      significant inverse association between the incidence of NHL and sunlight. The
      question of how to apply these findings to (public) health recommendations is
      discussed.

PMID- 16904315
TI  - Towards a pan-European consensus on the treatment of patients with colorectal
      liver metastases.
AB  - Colorectal cancer (CRC) caused nearly 204,000 deaths in Europe in 2004. Despite
      recent advances in the treatment of advanced disease, which include the
      incorporation of two new cytotoxic agents irinotecan and oxaliplatin into first
      line regimens, the concept of planned sequential therapy involving three active
      agents during the course of a patient's treatment and the integrated use of
      targeted monoclonal antibodies, the 5-year survival rates for patients with
      advanced CRC remain unacceptably low. For patients with colorectal liver
      metastases, liver resection offers the only potential for cure. This review,
      based on the outcomes of a meeting of European experts (surgeons and medical
      oncologists), considers the current treatment strategies available to patients
      with CRC liver metastases, the criteria for the selection of those patients most
      likely to benefit and suggests where future progress may occur.

PMID- 16904317
TI  - Convenient synthesis of 3- and 6-deoxy-D-myo-inositol phosphate analogues from
      (+)-epi- and (-)-vibo-quercitols.
AB  - Starting from (+)-epi- and (-)-vibo-quercitols readily produced by bioconversion
      of myo-inositol, some biologically interesting phosphate and polyphosphate
      analogues, including the Ins(1,4,5)P(3) derivatives of 3-deoxy- and 6-deoxy-D-myo
      inositol, could be readily prepared in a conventional manner. In addition,
      chemical modification at C-2 of the 3-deoxy Ins(1,4,5)P(3) provided 2-epimer, and
      2-deoxy and 2-deoxy-2-fluoro forms. Eight polyphosphate analogues obtained were
      assayed for biological activity against PDH-Pase and PDH-K, and G6Pase, but none
      proved positive.

PMID- 16904316
TI  - New, potent P1/P2-morpholinone-based HIV-protease inhibitors.
AB  - We have developed efficient synthesis of morpholinone-based cyclic mimetics of
      the P1/P2 portion of the HIV-1 protease inhibitor Amprenavir. This effort led to
      discovery of allyl- and spiro-cyclopropyl-P2-substituted inhibitors 17 and 31,
      both 500 times more potent than the parent inhibitor 1. These results support
      morpholinones as novel mimetics of the P1/P2 portion of Amprenavir and
      potentially of other HIV-protease inhibitors, and thus provide a novel medicinal
      chemistry template for optimization toward more potent and drug-like inhibitors.

PMID- 16904318
TI  - Novel benzimidazole-based MCH R1 antagonists.
AB  - The identification of an MCH R1 antagonist screening hit led to the optimization
      of a class of benzimidazole-based MCH R1 antagonists. Structure-activity
      relationships and efforts to optimize pharmacokinetic properties are detailed
      along with the demonstration of the effectiveness of an MCH R1 antagonist in an
      animal model of obesity.

PMID- 16904319
TI  - Synthesis and neuroprotective effects of serofendic acid analogues.
AB  - Analogues of serofendic acid were prepared and their protective effects against L
      glutamate (Glu)-induced neurotoxicity were examined using primary cultures of rat
      cortical neurons. Some analogues exhibited similar neuroprotective activity to
      that of serofendic acid.

PMID- 16904320
TI  - Cell surface-associated mucins in signal transduction.
AB  - Mucins are heavily glycosylated high molecular weight glycoproteins, which are
      involved in the protection and lubrication of luminal epithelial surfaces.
      Transmembrane mucins also engage in signal transduction, through extracellular
      domain-mediated ligand binding or by interacting with receptors for growth and
      differentiation factors. The cytoplasmic tail of MUC1 (MUC1CT), the best
      characterized of the transmembrane mucins, is involved in several signaling
      pathways, including those involving Ras, beta-catenin, p120 catenin, p53 and
      estrogen receptor alpha. MUC1CT also forms complexes with transcription factors,
      and then translocates to the nucleus by an unknown mechanism, where it is
      believed to influence the transcription of their target genes. MUC1CT has also
      been proposed to localize to mitochondrial membranes under conditions of
      genotoxic stress, where it attenuates the apoptotic pathway in response and
      confers resistance to apoptosis-inducing drugs.

PMID- 16904321
TI  - Tip60 in DNA damage response and growth control: many tricks in one HAT.
AB  - The Tip60 histone acetyltransferase is part of an evolutionarily conserved
      multisubunit complex, NuA4, which is recruited by many transcription factors to
      their target promoters, where it is thought to participate in histone acetylation
      and transcriptional activation. These transcription factors include tumor
      promoters and also tumor suppressors, such as p53, which links Tip60 to DNA
      damage responses. Tip60 also has transcription-independent roles in DNA damage
      responses. First, independently from NuA4, Tip60 binds the kinases ataxia
      telangiectasia mutated (ATM) and DNA-dependent protein kinase catalytic subunit
      (DNA-PKcs) and participates in their activation by DNA double-strand breaks.
      Second, NuA4 is recruited to the chromatin surrounding the breaks and, through a
      series of chromatin modifications, contributes to the dynamics of DNA repair.
      These molecular activities might endow Tip60 with multiple and potentially
      antagonistic biological functions.

PMID- 16904322
TI  - Emergency department patient classification systems: A systematic review.
AB  - BACKGROUND: The emergency department is a dynamic environment with a high
      throughput of patients. The clinical stability of patients varies considerably.
      In order to provide optimal care for patients a responsive staffing pattern is
      required. There is a need for a valid and reliable, prospective, emergency
      department patient classification system to set adequate nurse staffing levels in
      the UK. AIMS AND OBJECTIVES: To conduct a systematic review of the literature and
      determine the validity, reliability, strengths and weaknesses of emergency
      department patient classification systems. METHODS: The following electronic
      databases were searched for years 1985-2004: MEDLINE; CINAHL; COCHRANE Library
      databases DARE, CDSR, CCTR, BioMedNet Reviews, National Research Register (NRR).
      Manual searches were also conducted and relevant references retrieved from those
      listed in key papers, reports, theses and dissertations. Studies were also
      retrieved by contacting researchers in the field. RESULTS: Twelve patient
      classification systems met all the inclusion criteria. Only three systems
      reported evidence of good validity and reliability: the ED Patient Needs Matrix
      developed in the US, the Conner's Tool (a modified version of the ED Patient
      Needs Matrix) developed in Australia and the Jones Dependency Tool developed in
      the UK. CONCLUSION: There are very few patient classification systems developed
      for use in the ED setting that have demonstrated good validity and reliability.
      The Jones Dependency Tool is a simple, easy to use prospective, patient
      classification system that has demonstrated good validity and reliability in the
      UK.

PMID- 16904323
TI  - Patient dependency in the emergency department (ED): reliability and validity of
      the Jones Dependency Tool (JDT).
AB  - BACKGROUND: Rising patient demand in emergency departments is an international
      problem. Patient dependency (the degree of nursing care required) has major
      implications for nursing. Nurse skill mix and staffing levels can be addressed
      more effectively when dependency can be measured. A valid and reliable method of
      determining patient dependency in the emergency department in the United Kingdom
      is required. AIM: To test the validity, reliability and generalisability of the
      Jones Dependency Tool. METHODS: Six emergency departments across England were
      included. The sample was 140 adult patients from each site (n=840). Information
      was collected by nurses on: demographics, triage, chief complaint, vital clinical
      signs, nurse's own subjective rating of patient dependency, Jones Dependency Tool
      ratings and a comparative tool ratings. For a sub-sample of 40 patients,
      observation data were collected. RESULTS: There was a highly significant
      correlation between the Jones Dependency Tool scores and the nurses' subjective
      ratings of patient dependency (R=0.786,P<0.001). There was a significant
      correlation between triage rating and Jones Dependency Tool scores
      (R=0.58,P<0.001). The higher the dependency, the higher the proportion of
      patients with abnormal pulse rates (chi2=7.45,df=1,P=0.006), abnormal respiratory
      rates (chi2=15.683,df=1,P<0.001) and abnormal oxygen saturation
      (chi2=15.583,df=1,P<0.001). The higher the amount of time spent by nurses in
      direct care of patients the higher the patient's level of dependency
      (R=0,72,P<0.001). Length of time spent by nurses with patients was also
      significantly and positively correlated with the nurses' subjective ratings of
      patient dependency (R=0.49,P=0.001). There was a positive and significant
      correlation between Jones Dependency Tool scores and comparator scores
      (R=0.726,P<0.001). There was a good correlation between JDT scores measured over
      time (kappa=0.68) and good inter-rater reliability (kappa=0.75). CONCLUSIONS: The
      Jones Dependency Tool can be recommended as a valid and reliable tool for the
      measurement of patient dependency in the emergency department.

PMID- 16904324
TI  - Phosphorylation of L1-type cell-adhesion molecules--ankyrins away!
AB  - Neural cell-adhesion molecules (CAMs) are powerful initiators of neurite
      outgrowth during neural differentiation. In addition, their interactions with
      cytoskeletal components are often conserved and highly regulated. How these two
      aspects of neural CAM function relate to each other is not well understood.
      However, a recent publication from the Felsenfeld laboratory (
      http://www.mssm.edu/labs/felsenfeld) fills a gap in our knowledge of how the
      interaction of L1-type CAMs with the membrane skeleton adaptor protein ankyrin is
      severed by phosphorylation and suggests a feedback mechanism whereby the neurite
      stimulating activity of L1-CAM is inversely connected to its cytoskeleton
      binding.

PMID- 16904325
TI  - In vitro activity of novel dual action MDR anthranilamide modulators with
      inhibitory activity at CYP-450.
AB  - Synthesis and in vitro cytotoxicity assays of new anthranilamide MDR modulators
      have been performed to assess their inhibition potency of the P-glycoprotein (P
      gp) transporter. The aromatic spacer group between nitrogen atoms (N1 and N2) in
      the known inhibitor XR9576 was replaced with a flexible alkyl chain of 2 to 6
      carbon atoms in length. 6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinoline and their
      open-chain N-methylhomoveratrylamine counterparts were shown to be potent P-gp
      inhibitors. The maximal inhibition was obtained when using an ethyl or propyl
      spacer. Several compounds were more potent than verapamil and intrinsically less
      cytotoxic than XR9576. In addition, in vitro metabolism studies of 23a with a
      subset of human CYP-450 isoforms revealed that, unlike XR9576, 23a inhibited
      CYP3A4, an enzyme that colocalizes with P-gp in the intestine and contributes to
      tumor cell chemoresistance by enhancing the biodisposition of anticancer drugs
      such as paclitaxel toward metabolism. In this context, 22a might be a suitable
      candidate for further drug development.

PMID- 16904326
TI  - Carbocyclic pyrimidine nucleosides as inhibitors of S-adenosylhomocysteine
      hydrolase.
AB  - The design, synthesis, and unexpected inhibitory activity against S-adenosyl
      homocysteine (SAH) hydrolase (SAHase, EC 3.3.1.1) for a series of truncated
      carbocyclic pyrimidine nucleoside analogues is presented. Of the four nucleosides
      obtained, 10 was found to be active with a Ki value of 5.0 microM against SAHase.

PMID- 16904327
TI  - Tricyclic etheno analogs of PMEG and PMEDAP: synthesis and biological activity.
AB  - A series of novel 9-substituted (2-(3H-imidazo[1,2-a]purin-3
      yl)ethoxy)methylphosphonic and 4-substituted (2-(1H-imidazo[2,1-b]purin-1
      yl)ethoxy)methylphosphonic acids as tricyclic etheno analogs of potent antivirals
      and cytostatics PMEG and PMEDAP was synthesized and evaluated for their
      biological activity. Most of the compounds showed modest activity against
      varicella-zoster virus (VZV) and human cytomegalovirus (HCMV) except for (2-(9
      oxo-5,9-dihydro-3H-imidazo[1,2-a]purin-3-yl)ethoxy)methylphosphonic acid 8 which
      proved markedly active against VZV and HCMV. None of the compounds tested
      exhibited any significant cytostatic effect.

PMID- 16904329
TI  - Design and synthesis of 3,4-methylenedioxy-6-nitrophenoxyacetylhydrazone
      derivatives obtained from natural safrole: new lead-agents with analgesic and
      antipyretic properties.
AB  - In this work, we reported the synthesis and evaluation of the analgesic, anti
      inflammatory, and antipyretic properties of new 2-(6-nitro-benzo[1,3]dioxol-5
      yloxy)-acetylhydrazone derivatives (3), designed exploring molecular
      hybridization and isosteric replacement approaches between nimesulide (1) and
      carbanalogue NAH series (2) developed at LASSBio. Target compounds were
      synthesized in very good yields exploiting abundant Brazilian natural product
      safrole (4) as starting material. The evaluation of the antinociceptive
      properties of this series led us to discover a new potent prototype of analgesic
      and antipyretic agent, that is, NAH derivative 3c, named LASSBio-891, which
      showed to be more potent than dipyrone used as standard.

PMID- 16904328
TI  - Design, synthesis, and BK channel-opening activity of hexahydrodibenzazepinone
      derivatives.
AB  - In order to explore new scaffolds for large-conductance Ca2+ -activated K+
      channel (BK channel) openers, we carried out molecular design and synthesis on
      the basis of the following two concepts: (1) introduction of a heteroatom into
      the dehydroabietic acid (BK channel opener) skeleton would allow easier
      introduction of substituents. (2) Because of the fourfold symmetrical structure
      of BK channels, dimeric compounds in which two pharmacophores are linked through
      a tether are expected to have a greater binding probability to the channels,
      resulting in increased channel-opening activity. Herein, we explore the
      usefulness of the hexahydrodibenzazepinone structure as a new scaffold for BK
      channel openers. The synthesized monomer compounds of hexahydrodibenzazepinone
      derivatives, which can be derived from dehydroabietic acid, were subjected to
      electrophysiological patch-clamp studies, followed by Magnus contraction
      relaxation assay using rabbit urinary bladder smooth muscle strips to assess
      overall activities. Dimeric compounds were designed by linking the monomeric
      hexahydrodibenzazepinone derivatives through a diacetylenebenzene tether, and
      their channel-opening activities were evaluated by electrophysiological methods.
      Finally, we concluded that the critical structure for BK channel-opening activity
      is the hexahydrodibenzazepinone monomer substituted with a phenyl-bearing alkynyl
      substituent on the lactam amide.

PMID- 16904330
TI  - A new dihydroxanthenone from a plant-associated strain of the fungus Chaetomium
      globosum demonstrates anticancer activity.
AB  - Bioassay-guided fractionation of a cytotoxic EtOAc extract of the fungal strain,
      Chaetomium globosum, inhabiting the rhizosphere of the Christmas cactus, Opuntia
      leptocaulis, of the Sonoran desert afforded a new dihydroxanthenone,
      globosuxanthone A (1), a new tetrahydroxanthenone, globosuxanthone B (2), two new
      xanthones, globosuxanthone C (3) and D (4), 2-hydroxyvertixanthone (5), and two
      known anthraquinones (6 and 7). The structures of the new compounds 1-4 were
      elucidated by NMR and MS techniques, and the relative stereochemistry of 1 was
      determined by X-ray crystallographic analysis. Of the compounds encountered, 1
      was found to exhibit strong cytotoxicity against a panel of seven human solid
      tumor cell lines, disrupt the cell cycle leading to the accumulation of cells in
      either G2/M or S phase, and induce classic signs of apoptosis.

PMID- 16904331
TI  - Synthesis and biological evaluation of a novel class of rofecoxib analogues as
      dual inhibitors of cyclooxygenases (COXs) and lipoxygenases (LOXs).
AB  - A group of 4-(4-methanesulfonylphenyl)-3-phenyl-2(5H)furanones possessing an
      acetyl, 3-oxobut-1-ynyl, [hydroxyl(or alkoxy)imino]alkyl, [hydroxyl(or
      alkoxy)imino]alkynyl, and N-alkoxy(or N-phenoxy)carbonyl-N-hydroxy-N-ethylamino
      substituents at the para-position of the C-3 phenyl ring of rofecoxib were
      synthesized. This group of compounds was designed for evaluation as dual
      inhibitors of cyclooxygenases (COXs) and lipoxygenases (LOXs) that exhibit in
      vivo anti-inflammatory and analgesic activities. In vitro COX-1/COX-2, and 5
      LOX/15-LOX, isozyme inhibition structure-activity relationships identified 3-[4
      (1-hydroxyimino)ethylphenyl]-4-(4-methanesulfonylphenyl)-2(5H)furanone (17a)
      having an optimal combination of COX-2 (COX-2 IC50 = 1.4 microM; COX-2 SI > 71),
      and 5-LOX and 15 LOX (5-LOX IC50 = 0.28 microM; 15-LOX IC50 = 0.32 microM),
      inhibitory effects. It was also discovered that 3-[4-(3-hydroxyiminobut-1
      ynyl)phenyl]-4-(4-methanesulfonylphenyl)-2(5H)furanone (18a) possesses dual COX-2
      (IC50 = 2.7 microM) and 5-LOX (IC50 = 0.30 microM) inhibitor actions. Further in
      vivo studies employing a rat carrageenan-induced paw edema model showed that the
      oxime compounds (17a, 18a) were more potent anti-inflammatory agents than the 5
      LOX inhibitor caffeic acid, and 15-LOX inhibitor nordihydroguaiaretic acid
      (NDGA), but less potent than the selective COX-2 inhibitor celecoxib. The results
      of this investigation showed that incorporation of a para-oxime moiety on the C-3
      phenyl ring of rofecoxib provides a suitable template for the design of dual
      inhibitors of the COX and LOX enzymes.

PMID- 16904332
TI  - 5-Substituted-2,3-diphenyltetrahydrofurans: a new class of moderately selective
      COX-2 inhibitors.
AB  - The nature of C-5 substituent and the configuration at C-5 carbon of 2,3
      diphenyltetrahydrofurans, with chiral centres at C-2, C-3 and C-5, show a
      remarkable influence on their COX-2 inhibition and selectivity. Out of the eight
      compounds investigated here, 1b with COOH group and R* configuration at C-5, and
      2d with CH2SCH2CH3 group and S* configuration at C-5 have been identified as lead
      molecules for further studies on COX-2 inhibition.

PMID- 16904333
TI  - Substituent activity relationship studies on new azolo benzoxazepinyl
      oxazolidinones.
AB  - In an effort to discover potent antibacterials based on the entropically favored
      'bioactive conformation' approach, a series of novel tricyclic molecules
      mimicking the conformationally constrained structure of Linezolid is reported.
      Based on the initial tricyclic molecule 1, the benzazepine derivative 2 was
      designed where the tricyclic structure had more flexibility around C-N bond
      compared to 1. While, the molecule 2 was less active, the molecule 3 showed
      promising antibacterial activity presumably after having obtained rigidity due to
      pyrrole ring. The syntheses, SAR studies, and evaluation of 3 as a lead compound
      are reported.

PMID- 16904334
TI  - The photochemical reaction cycle of retinal reconstituted bacteriorhodopsin.
AB  - The function of three types of bacteriorhodopsins was compared: the wild-type,
      the bleached and retinal reconstituted and retinal deficient bacteriorhodopsin
      after retinal addition. The apparent pK(a) of the proton acceptor group for the
      bleached BR and retinal deficient BR shifted toward higher pH values compared to
      the wild-type BR. Fitting the photocycle model to the absorption kinetic signals
      for all three proteins showed the existence of the same intermediates, but the
      time-dependent concentration of the intermediates was different. Although
      measurements were made at pH 7, the absorption kinetics and photoelectric signals
      in both retinal reconstituted samples acted as wild-type bacteriorhodopsin at
      significantly higher pH. Below pH 3 the retinal deficient and reconstituted
      sample bleached. These results suggested that the added retinal was not able to
      rebind in the same position in the protein as in native bacteriorhodopsin. This
      points out that care should be taken, when bleached bacteriorhodopsin is
      reconstituted with different retinal analogs.

PMID- 16904335
TI  - C-type natriuretic peptide and heart failure.
AB  - C-type natriuretic peptide (CNP) is a peptide produced by the vascular
      endothelium with vasodilative properties. It shares structural and physiological
      properties with the atrial and brain natriuretic peptides (ANP and BNP), whose
      central role in the pathophysiology of heart failure (CHF) is firmly established.
      The role of CNP, first isolated from porcine brain, has not been yet completely
      determined. The transcription of the gene, that in man is located on chromosome
      2, is regulated by factors such as tumor necrosis factor and interleukin-1. Two
      mature forms of the peptide exist: CNP-53, that predominates in tissues and CNP
      22, found mainly in plasma. As recently found, CNP is produced directly in the
      myocardium and an increase in plasma levels of this peptide and of its precursor
      was observed in CHF. The aim of this review was to examine the current literature
      relating to cardiovascular functions of CNP and in particular to its role in CHF.
      In fact, CNP may represent an important new local autocrine and endocrine
      mediator in CHF although further evaluations are required to define its full
      pathophysiological role in this disease.

PMID- 16904336
TI  - Picolinyl ester fragmentation mechanism studies with application to the
      identification of acylcarnitine acyl groups following transesterification.
AB  - Acyl picolinyl esters provide excellent data to identify the structures of acyl
      groups. However, the mechanisms for the formation of fragment ions from picolinyl
      esters are unsettled. Proposed structures for fragment ions have focused on long
      chain groups and may not accommodate results from medium- and short-chain acyl
      groups. Using deuterium-labeled organic acids, we have investigated the
      mechanisms for the formation of fragment ions. Based on these studies, we propose
      a new mechanism that is consistent with the experimental data. We then tested the
      mechanisms by analyzing selected acylcarnitines. Transesterification of
      acylcarnitines was performed by reaction with 3-pyridylcarbinol and potassium
      tert-butoxide in dichloromethane to produce acyl picolinyl esters. The picolinyl
      esters were separated and detected by gas chromatography/electron ionization-mass
      spectrometry. Each mass spectrum contained a series of peaks with m/z differences
      of 12, 13, or 14 u depending on the acyl group's chemical structure. The position
      of an unsaturated bond or branched methyl in the acyl group of acylcarnitine can
      be readily determined.

PMID- 16904337
TI  - Use of a double resonance electron capture dissociation experiment to probe
      fragment intermediate lifetimes.
AB  - The relative abundances of fragment ions in electron capture dissociation (ECD)
      are often greatly affected by the secondary and tertiary structures of the
      precursor ion, and have been used to derive the gas-phase conformations of the
      protein ions. In this study, it is found that resonance ejection of the charge
      reduced molecular ion during ECD resulted in significant changes in many fragment
      ion populations. The ratio of the ion peak intensities in the double resonance
      (DR)-ECD to that in the normal ECD experiment can be used to calculate the
      lifetime of the radical intermediates from which these fragments are derived.
      These lifetimes are often in the ms range, a time sufficiently long to facilitate
      multiple free radical rearrangements. These ratios correlate with the
      intramolecular noncovalent interactions in the precursor ion, and can be used to
      deduce information about the gas-phase conformation of peptide ions. DR-ECD
      experiments can also provide valuable information on ECD mechanisms, such as the
      importance of secondary electron capture and the origin of c./z ions.

PMID- 16904338
TI  - ESI-FTICR-MS studies on gas phase fragmentation reactions of ArPd(PPh3)2I
      complexes.
AB  - Gas-phase fragmentation reactions of [ArPd(PPh3)2]+ were studied by electrospray
      ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI-FTICR
      MS). The results of sustained off-resonance irradiation collision-activated
      dissociation (SORI-CAD) experiments provide detailed insights into mechanisms for
      the gas-phase fragmentation reactions of these complex ions. The PC bond cleavage
      mediated by palladium is investigated in the gas phase. There are two competitive
      fragmentation pathways for the complex ions [ArPd(PPh3)2]+ (Ar = p-OCH3-C6H4, p
      CH3-C6H4, p-tBu-C6H4, p-NH2-C6H4, p-COCH3-C6H4, and p-F-C6H4) of electron
      donating and electron-withdrawing aromatic iodides. Path A proceeds through
      reductive elimination of [ArPd(PPh3)2]+ to produce the product ion [PPh3Ar]+.
      Path B mostly proceeds via phenyl migration from the triphenylphosphine ligand to
      the palladium center by cleavage of the phosphorus-phenyl bond to give a
      palladium-phenyl intermediate, and subsequent reductive elimination of the
      intermediate to yield a product ion [PPh4]+. The result of deuterium-labeling
      experiments provides evidence for the phenyl shift between the palladium center
      and the coordinated ligand through cleavage of the PC bond. The complex ions [(o
      CH3-C6H4)Pd(PPh3)2]+, [(o-2,6-Me2-C6H3)Pd(PPh3)2]+, and [(C10H7)Pd(PPh3)2]+
      display more fragmentation pathways, two of which are similar to those of the
      ions [ArPd(PPh3)2]+ (Ar = p-OCH3-C6H4, p-CH3-C6H4, p-tBu-C6H4, p-NH2-C6H4, p
      COCH3-C6H4, p-F-C6H4), and the third pathway involves loss of one molecule of
      benzene and one PPh3 ligand. The electronic effect and steric effect of the aryl
      groups also exhibit different influences on the fragmentation pathways.

PMID- 16904339
TI  - Probing RNA hairpins with cobalt(III)hexammine and electrospray ionization mass
      spectrometry.
AB  - In this work, electrospray ionization mass spectrometry (ESI MS) was employed to
      study the interactions of cobalt(III) hexammine, Co(NH3)6(3+), with five RNA
      hairpins representing the 790 loop of 16S ribosomal RNA and 1920 loop of 23S
      ribosomal RNA. The RNAs varied in mismatch identity (G.U versus A.C) and level of
      base modification (pseudouridine versus uridine). Co(NH3)6(3+) binding was
      observed with the four RNA hairpins that contained a G.U wobble pair in the stem
      region. ESI MS revealed 1:1 and 1:2 complex formation with all RNAs. Weaker
      binding was observed with the fifth RNA hairpin that contained an A.C wobble pair
      in the stem region. The effects of pH on Co(NH3)6(3+) binding were also examined.

PMID- 16904340
TI  - The role of NK cell recognition of nectin and nectin-like proteins in tumor
      immunosurveillance.
AB  - Natural killer (NK) cells have important functions in the innate immunity to
      tumors. Recognition of tumor cells by NK cells is mediated by the interaction of
      activating and inhibitory NK cell receptors with ligands expressed on the tumor
      target. In addition, NK cell-target cell interactions require the engagement of
      adhesion molecules that stabilize the cell-cell conjugate. Recently, several
      novel NK cell receptors have been reported to regulate NK cell adhesion and
      activation through interaction with ligands of the nectin and nectin-like (Necl)
      family of adhesion molecules. We here review current knowledge on these
      receptors, CD226, CD96 and CRTAM, and their role in tumor immunosurveillance.

PMID- 16904341
TI  - UCSF tomography: an integrated software suite for real-time electron microscopic
      tomographic data collection, alignment, and reconstruction.
AB  - A real-time alignment and reconstruction scheme for electron microscopic
      tomography (EMT) has been developed and integrated within our UCSF tomography
      data collection software. This newly integrated software suite provides full
      automation from data collection to real-time reconstruction by which the three
      dimensional (3D) reconstructed volume is immediately made available at the end of
      each data collection. Real-time reconstruction is achieved by calculating a
      weighted back-projection on a small Linux cluster (five dual-processor compute
      nodes) concurrently with the UCSF tomography data collection running on the
      microscope's computer, and using the fiducial-marker free alignment data
      generated during the data collection process. The real-time reconstructed 3D
      volume provides users with immediate feedback to fully asses all aspects of the
      experiment ranging from sample choice, ice thickness, experimental parameters to
      the quality of specimen preparation. This information can be used to guide
      subsequent data collections. Access to the reconstruction is especially useful in
      low-dose cryo EMT where such information is very difficult to obtain due to
      extraordinary low signal to noise ratio in each 2D image. In our environment, we
      generally collect 2048 x 2048 pixel images which are subsequently computationally
      binned four-fold for the on-line reconstruction. Based upon experiments performed
      with thick and cryo specimens at various CCD magnifications (50000x-80000x),
      alignment accuracy is sufficient to support this reduced resolution but should be
      refined before calculating a full resolution reconstruction. The reduced
      resolution has proven to be quite adequate to assess sample quality, or to screen
      for the best data set for full-resolution reconstruction, significantly improving
      both productivity and efficiency of system resources. The total time from start
      of data collection to a final reconstructed volume (512 x 512 x 256 pixels) is
      about 50 min for a +/-70 degrees 2k x 2k pixel tilt series acquired at every 1
      degrees.

PMID- 16904342
TI  - Using two-dimensional spatial information in decomposition of surface EMG
      signals.
AB  - Recently, high-density surface EMG electrode grids and multi-channel amplifiers
      became available for non-invasive recording of human motor units (MUs). We
      present a way to decompose surface EMG signals into MU firing patterns, whereby
      we concentrate on the importance of two-dimensional spatial differences between
      the MU action potentials (MUAPs). Our method is exemplified with high-density EMG
      data from the vastus lateralis muscle of a single subject. Bipolar and Laplacian
      spatial filtering was applied to the monopolar raw signals. From the single
      recording in this subject six different simultaneously active MUs could be
      distinguished using the spatial differences between MUAPs in the direction
      perpendicular to the muscle fiber direction. After spike-triggered averaging, 125
      channel two-dimensional MUAP templates were obtained. Template-matching allowed
      tracking of all MU firings. The impact of spatial information was measured by
      using subsets of the MUAP templates, either in parallel or perpendicular to the
      muscle fiber direction. The use of one-dimensional spatial information
      perpendicular to the muscle fiber direction was superior to the use of a linear
      array electrode in the longitudinal direction. However, to detect the firing
      events of the MUs with a high accuracy, as needed for instance for estimation of
      firing synchrony, two-dimensional information from the complete grid electrode
      appears essential.

PMID- 16904343
TI  - In vivo behavior of muscle fascicles and tendinous tissues of human gastrocnemius
      and soleus muscles during twitch contraction.
AB  - The present study investigated the differences between the human medial
      gastrocnemius (MG) and soleus (SOL) muscles in length changes of muscle fascicles
      and tendinous tissues during twitch contraction induced by an electrical nerve
      stimulus. Also, the time-course characteristics of twitch torque were related
      with changes in the length of muscle fascicles and tendinous tissues. No
      significant difference was observed between MG and SOL in contraction and half
      relaxation times of the changes in lengths and velocities of both muscle
      fascicles and tendinous tissues. The time-course of changes in twitch torque was
      nearly identical to that of the length of muscle fascicles and tendinous tissues.
      It was suggested that the behavior of MG and SOL during twitch contraction is
      practically similar in spite of their known physiological and architectural
      differences, and that the time-course of twitch torque is greatly influenced by
      the changes in the length of muscle fascicles and tendinous tissues.

PMID- 16904344
TI  - The right hippocampus participates in short-term memory maintenance of object
      location associations.
AB  - Doubts have been cast on the strict dissociation between short- and long-term
      memory systems. Specifically, several neuroimaging studies have shown that the
      medial temporal lobe, a region almost invariably associated with long-term
      memory, is involved in active short-term memory maintenance. Furthermore, a
      recent study in hippocampally lesioned patients has shown that the hippocampus is
      critically involved in associating objects and their locations, even when the
      delay period lasts only 8 s. However, the critical feature that causes the medial
      temporal lobe, and in particular the hippocampus, to participate in active
      maintenance is still unknown. This study was designed in order to explore
      hippocampal involvement in active maintenance of spatial and non-spatial
      associations. Eighteen participants performed a delayed-match-to-sample task in
      which they had to maintain either object-location associations, color-number
      association, single colors, or single locations. Whole-brain activity was
      measured using event-related functional magnetic resonance imaging and analyzed
      using a random effects model. Right lateralized hippocampal activity was evident
      when participants had to maintain object-location associations, but not when they
      had to maintain object-color associations or single items. The present results
      suggest a hippocampal involvement in active maintenance when feature combinations
      that include spatial information have to be maintained online.

PMID- 16904345
TI  - Movement-related desynchronization-synchronization (ERD/ERS) in patients with
      Unverricht-Lundborg disease.
AB  - We studied changes in event-related desynchronization/synchronization (ERD/ERS)
      patterns in patients with Unverricht-Lundborg disease (ULD), presenting with
      prominent action myoclonus. We analyzed the movement-related ERD/ERS in alpha and
      beta frequency bands in 15 patients using self-paced finger extension as a motor
      paradigm and we compared the results with those obtained in 12 healthy
      volunteers. In all ULD patients, alpha- and beta-ERD regularly occurred with
      onset and location similar to that found in healthy controls, but the
      desynchronization of alpha activity was significantly greater than in controls
      (C3: -64.4+/-9.8% vs. -49.7+/-14.8%; p=0.004). Moreover, in the patients, both
      alpha- and beta-ERD spread toward frontal electrodes. In controls, the post
      movement beta-ERS regularly occurred; it was absent in eight patients with severe
      action myoclonus, while, in seven patients with mild or moderate myoclonus, the
      beta-peak was significantly smaller with respect to that measured in controls
      (55.6+/-15.1% vs. 153.9+/-99.8%, p=0.006). The failure of beta-ERS well
      correlated with motor impairment resulting from action myoclonus, whereas SSEPs
      and long-loop reflexes performed to detect signs of cortical hyperexcitability
      showed inconsistent changes. In ULD patients, ERD/ERS changes indicate an
      increased activation of motor cortex during movement planning and a great
      reduction of post-excitatory inhibition of motor cortex. The changes involving
      beta-ERS had a significant relationship with the functional disability in
      individual patients and might play a pathogenic role in the motor dysfunction.

PMID- 16904346
TI  - Increased ghrelin levels in epileptic patients.

PMID- 16904347
TI  - Masked prosthetic graft to sigmoid colon fistula diagnosed by 18
      fluorodeoxyglucose positron emission tomography.
AB  - The diagnosis of low grade prosthetic graft infection or aorto-enteric fistula is
      difficult using conventional radiographic imaging modalities. We report a case of
      aorto-enteric fistula to the sigmoid colon diagnosed by the new technique of 18
      fluorodeoxyglucose positron emission tomography.

PMID- 16904348
TI  - Early allogeneic stem cell transplantation for chronic myelogenous leukemia in
      the imatinib era: a preliminary assessment.
AB  - We have examined the role of early allogeneic hematopoietic stem cell
      transplantation in patients with chronic phase chronic myelogenous leukemia (CML)
      who enter a complete cytogenetic remission with imatinib mesylate. Three kinds of
      data were used to examine the effect of the outcome of current BCR-ABL inhibitor
      treatment compared to early allogeneic stem cell transplantation: (1) the life
      expectancy of the general population of the United States as a function of age,
      (2) the life expectancy of CML patients as a function of the age of patients
      treated with imatinib mesylate (imatinib) who achieve a complete cytogenetic
      remission, and (3) the life expectancy of patients with CML treated with matched
      related or matched-unrelated stem cell transplantation as a function of age,
      derived from data provided by the Center for International Blood and Marrow
      Transplant Research (CIBMTR). We also considered separately the transplant
      results of the Fred Hutchinson Cancer Research Center (FHCRC), which are
      substantially better than the "average" outcome from the CIBMTR. We have
      calculated the projected life expectancy from the age at which patients with CML
      enter complete cytogenetic remission with imatinib and that of those who receive
      allogeneic stem cell transplantation. The outcome with imatinib therapy of newly
      diagnosed patients with CML has been documented for only 4 and 1/2 years, whereas
      transplant data were available for up to 25 years. Thus, in order to compare life
      expectancy and 10-year survival probability, it was necessary to extrapolate the
      imatinib data. A basis for extrapolation is offered and conservative estimates
      have been used for comparison. Our best estimate is that patients receiving
      imatinib who have a complete cytogenetic remission have a higher projected
      probability of 10-year survival than patients who are transplanted, based on
      results provided by the CIBMTR, and have about the same probability compared to
      the data from the Fred Hutchinson Cancer Center for patients in the 30- to 60
      year-old range. The mathematical approach used here permits reexamining the
      analysis using future data on BCR-ABL inhibitor therapy or allogeneic stem cell
      transplantation therapy or both.

PMID- 16904349
TI  - Stimulation of non-transferrin iron uptake by iron deprivation in K562 cells.
AB  - We tested the effect of iron deprivation on the uptake of iron from ferric
      citrate by human erythroleukemia K562 cells. The iron uptake after 24-h
      preincubation in defined iron-free medium was approximately 2-3x higher than
      after the preincubation in control transferrin-containing medium. The
      preincubation of K562 cells in iron-free medium together with the inhibitor of
      protein synthesis cycloheximide completely abrogated the stimulation of the iron
      uptake. The preincubation in iron-free medium resulted in a slight decrease (20%)
      of DMT1 mRNA level. The level of Dcytb, ferroportin and hephaestin mRNA did not
      exert any significant change. We also did not find any significant effect on the
      protein level of DMT1, Dcytb, ferroportin and hephaestin. We conclude that iron
      deprivation stimulates the uptake of non-transferrin iron in K562 cells and that
      this stimulation depends on protein synthesis. It seems that the expression of an
      unknown or seemingly unrelated protein(s) is involved.

PMID- 16904351
TI  - Construction of a contig of BAC clones spanning the region of the apple scab
      avirulence gene AvrVg.
AB  - The ascomycete Venturia inaequalis, causal pathogen of apple scab, underlies a
      gene-for-gene relationship with its host plant apple (Malus spp.). 'Golden
      Delicious', one of the most common cultivated apples in the world, carries the
      ephemeral resistance gene Vg. Avirulence gene AvrVg, matching resistance gene Vg
      has recently been mapped on the V. inaequalis genome. In this paper, we present
      the construction of a BAC library from a V. inaequalis AvrVg isolate. The library
      is composed of 7680 clones, with an average insert size of 80kb. By
      hybridization, it has been estimated that the library contains six haploid genome
      equivalents. Thus the V. inaequalis genome can be predicted to be approximately
      100Mb in size. A chromosome walk, starting from the marker VirQ5 co-segregating
      with AvrVg, has been performed using the BAC library. Twelve BAC clones were
      identified during four steps of the chromosome walking. The size of the resulting
      contig is approximately 330kb.

PMID- 16904352
TI  - Effects of etamsylate on equine platelets: in vitro and in vivo studies.
AB  - The aim of this study was to investigate whether etamsylate produces equine
      platelet activation. In vitro and in vivo studies were designed in which seven
      and eight adult healthy horses were included, respectively. In the in vitro
      study, citrated blood was incubated with different concentrations of etamsylate,
      and P-selectin expression and annexin V binding were determined by flow
      cytometry. In the in vivo study, blood was collected before and 1 and 2h after IV
      administration of etamsylate, and P-selectin expression was evaluated. In the in
      vitro study, a significant increase in P-selectin expression, leukocyte-platelet
      aggregate formation and annexin V binding were observed. In the in vivo study, a
      marked increase in P-selectin expression and heterotypic aggregate formation was
      seen in two and five horses, respectively, although no significant differences
      were detected when analyzing results from all the animals together. The results
      of the in vitro study indicate that etamsylate produces a pre-activation state in
      equine platelets, but this fact could be confirmed by the in vivo study.

PMID- 16904353
TI  - Foot-and-mouth disease - quantification and size distribution of airborne
      particles emitted by healthy and infected pigs.
AB  - There is strong evidence to suggest that foot-and-mouth disease (FMD) can be
      transmitted by airborne virus up to many kilometres from a virus source.
      Atmospheric dispersion models are often used to predict where this disease might
      spread. This study investigated whether FMD virus (FMDV) aerosol has specific
      characteristics which need to be taken into consideration in these models. The
      characteristics and infectiousness of particles emitted by 12 pigs have been
      studied pre- and post-infection with O UKG 2001 FMDV. Aerosol generated by
      individual pigs was found log normally distributed in the range 0.015-20.0microm
      with concentrations between 1000 and 10000cm(-3) at the smallest size and <1cm(
      3) above 10microm. No differences in either the total number of particles
      produced or their size distribution were detected between uninfected and infected
      pigs. However, a correlation between aerosol concentration and animal activity
      was found with a more active pig producing significantly greater concentrations
      than those that were less active. Viable virus was found up to a maximum of 6.3
      log TCID(50)/24h/animal. The virus was distributed almost equally across the
      three size ranges; <3, 3-6 and >6microm. No correlation could be established
      between the production of virus and animal activity. In general the production of
      airborne virus closely followed the detection of viraemia in the blood and the
      presence of clinical symptoms. However, in one instance a pig excreted as much
      airborne virus as the other animals in the study, but with less virus detected in
      its blood. The results suggest that there is little merit in including a
      sophisticated virus release pattern based on physical activity periods or FMDV
      aerosol size spectrum, together with the appropriate dry deposition calculations,
      in models used to predict airborne spread of FMD. An estimate of the total daily
      virus production based on the clinical assessment of disease and virus strain is
      sufficient as input.

PMID- 16904354
TI  - Tissue disposition of azithromycin after intravenous and intramuscular
      administration to rabbits.
AB  - Tissue disposition of azithromycin after intravenous (IV) or intramuscular (IM)
      injection at a single dose rate of 10mg/kg bodyweight were investigated in
      rabbits using a modified agar diffusion bioassay for determining tissue
      concentrations. The pharmacokinetic behaviour of azithromycin was characterized
      by low and sustained plasma concentrations but high and persistent tissue
      concentrations. Kinetic parameters indicated a high retention of the drug in
      peripheral compartments. The plasma half-lives after IV and IM administrations
      were similar being 21.8h and 23.1h, respectively, while the half-lives obtained
      in tissues after IV and IM administration were at least 1.4 and 1.9 times longer
      than in plasma, respectively. The highest tissue concentrations were found in
      bile, liver and spleen whereas the lowest ones were found in skeletal muscle
      (although they were higher than those in plasma). From the results of the single
      administration in this study an IM dosage regimen can be proposed that achieves
      minimum concentrations over 2mg/L in rabbits: three doses of 4-5mg/kg/day would
      provide suitable therapeutic concentrations in pulmonary tissues over seven days.

PMID- 16904355
TI  - Area-selective signal parameter estimation for two-dimensional MR spectroscopy
      data.
AB  - We consider the problem of parametric spectral analysis of two-dimensional (2D)
      magnetic resonance spectroscopy (MRS) data. Estimating the signal components from
      2D MRS data is becoming common practice in many clinical MR applications. The
      most frequently used signal processing tool for this estimation problem is the
      non-parametric 2D-FFT. There are several alternative parametric methods available
      to perform this analysis, yet their computational complexity is generally rather
      high and it becomes prohibitive when the number of points in the measured data
      matrix is large. In this paper, we propose a novel signal parameter estimation
      technique which operates on a pre-specified sub-area of the 2D spectrum. This
      area-selective approach can be used either to estimate only the signal components
      of main interest in the data, or to compute signal parameter estimates of all
      present signal components as the computational burden for each sub-area is low.
      In the numerical example section we consider both simulated data and in vitro 1H
      data acquired from a 1.5 T MR scanner.

PMID- 16904356
TI  - Encoding to the longitudinal magnetization for MR imaging and flow velocity
      mapping.
AB  - Phase-encoding to the longitudinal magnetization is implemented by adding
      encoding gradient pulses in the evolution period tau of the NMR pulse sequence 90
      degrees+x-tau-90 degrees-x. This work focuses on the effect of the spin-lattice
      relaxation and its removal and on the constraint that the 90 degrees-x pulse can
      only transform the phase of the transverse magnetization partially to the
      longitudinal magnetization. Theoretical analysis shows that the encoded phase
      information and the spin-lattice relaxation effect are separable and the latter
      is identical in each repetition in collecting phase-encoding data. Thus the
      relaxation effect can be eliminated by subtracting a second data set whose phase
      information is inverted or by alternating the polarity of the relaxation
      contribution. From data with partial phase information, Fourier-transform image
      reconstruction results in mirror aliasing in which the two halves of the Fourier
      spectrum of positive and negative coordinates overlap. Removal of mirror aliasing
      requires imaging data of the orthogonal component. Nevertheless mirror aliasing
      is not necessarily a problem, depending on the subject of study. Phase-encoding
      to the longitudinal magnetization for spatial MRI and flow velocity mapping are
      demonstrated using the rotating ultra-fast imaging sequence (RUFIS).

PMID- 16904357
TI  - Effect of dietary conjugated linoleic acid (CLA) on lipid composition, metabolism
      and gene expression in Atlantic salmon (Salmo salar) tissues.
AB  - Dietary conjugated linoleic acid (CLA) affects fat deposition and lipid
      metabolism in mammals, including livestock. To determine CLA effects in Atlantic
      salmon (Salmo salar), a major farmed fish species, fish were fed for 12 weeks on
      diets containing fish oil or fish oil with 2% and 4% CLA supplementation. Fatty
      acid composition of the tissues showed deposition of CLA with accumulation being
      2 to 3 fold higher in muscle than in liver. CLA had no effect on feed conversion
      efficiency or growth of the fish but there was a decreased lipid content and
      increased protein content after 4% CLA feeding. Thus, the protein:lipid ratio in
      whole fish was increased in fish fed 4% CLA and triacylglycerol in liver was
      decreased. Liver beta-oxidation was increased whilst both red muscle beta
      oxidation capacity and CPT1 activity was decreased by dietary CLA. Liver highly
      unsaturated fatty acid (HUFA) biosynthetic capacity was increased and the
      relative proportion of liver HUFA was marginally increased in salmon fed CLA. CLA
      had no effect on fatty acid Delta6 desaturase mRNA expression, but fatty acid
      elongase mRNA was increased in liver and intestine. In addition, the relative
      compositions of unsaturated and monounsaturated fatty acids changed after CLA
      feeding. CLA had no effect on PPARalpha or PPARgamma expression in liver or
      intestine, although PPARbeta2A expression was reduced in liver at 4% CLA feeding.
      CLA did not affect hepatic malic enzyme activity. Thus, overall, the effect of
      dietary CLA was to increase beta-oxidation in liver, to reduce levels of total
      body lipid and liver triacylglycerol, and to affect liver fatty acid composition,
      with increased elongase expression and HUFA biosynthetic capacity.

PMID- 16904358
TI  - Molecular characterization of lipoprotein lipase, hepatic lipase and pancreatic
      lipase genes: effects of fasting and refeeding on their gene expression in red
      sea bream Pagrus major.
AB  - To investigate the nutritional regulation of lipid metabolism in fish, molecular
      characterization of lipases was conducted in red sea bream Pagrus major, and the
      effects of fasting and refeeding on their gene expression was examined. Together
      with data from a previous study, a total of four lipase genes were identified and
      characterized as lipoprotein lipase (LPL), hepatic lipase (HL) and pancreatic
      lipase (PL). These four lipase genes, termed LPL1, LPL2, HL and PL, share a high
      degree of similarity. LPL1 and LPL2 genes were expressed in various tissues
      including adipose tissue, gill, heart and hepatopancreas. HL gene was exclusively
      expressed in hepatopancreas. PL gene expression was detected in hepatopancreas
      and adipose tissue. Red sea bream LPL1 and LPL2 gene expression levels in
      hepatopancreas were increased during 48 h of fasting and decreased after
      refeeding, whereas no significant change in the expression levels of LPL1 and
      LPL2 was observed in adipose tissue, indicating that LPL1 and LPL2 gene
      expression is regulated in a tissue-specific manner in response to the
      nutritional state of fish. HL and PL gene expression was not affected by fasting
      and refeeding. The results of this study suggested that LPL, HL and PL gene
      expression is under different regulatory mechanisms in red sea bream with respect
      to the tissue-specificities and their nutritional regulation.

PMID- 16904359
TI  - Role of energetic coenzyme pools in the production of L-carnitine by Escherichia
      coli.
AB  - The aim of this work was to understand the steps controlling the
      biotransformation of trimethylammonium compounds into L(-)-carnitine by
      Escherichia coli. The high-cell density reactor steady-state levels of carbon
      source (glycerol), biotransformation substrate (crotonobetaine), acetate
      (anaerobiosis product) and fumarate (as an electron acceptor) were pulsed by
      increasing them fivefold. Following the pulse, the evolution of the enzyme
      activities involved in the biotransformation process of crotonobetaine into L(-)
      carnitine (crotonobetaine hydration), in the synthesis of acetyl-CoA (ACS: acetyl
      CoA synthetase and PTA: ATP: acetate phosphotransferase) and in the distribution
      of metabolites for the tricarboxylic acid (ICDH: isocitrate dehydrogenase) and
      glyoxylate (ICL: isocitrate lyase) cycles was monitored. In addition, the levels
      of carnitine, the cell ATP content and the NADH/NAD(+) ratio were measured in
      order to assess the importance and participation of these energetic coenzymes in
      the catabolic system. The results provided an experimental demonstration of the
      important role of the glyoxylate shunt during biotransformation and the need for
      high levels of ATP to maintain metabolite transport and biotransformation.
      Moreover, the results obtained for the NADH/NAD(+) pool indicated that it is
      correlated with the biotransformation process at the NAD(+) regeneration and ATP
      production level in anaerobiosis. More importantly, a linear correlation between
      the NADH/NAD(+) ratio and the levels of the ICDH and ICL (carbon and electron
      flows) and the PTA and ACS (acetate and ATP production and acetyl-CoA synthesis)
      activity levels was assessed. The main metabolic pathway operating during cell
      metabolic perturbation with a pulse of glycerol and acetate in the high-cell
      density membrane reactor was that related to ICDH and ICL, both regulating the
      carbon metabolism, together with PTA and ACS enzymes (regulating ATP production).

PMID- 16904360
TI  - Estradiol stimulates the biosynthetic pathways of breast cancer cells: detection
      by metabolic flux analysis.
AB  - Selective estrogen receptor (ER) modulators are highly successful breast cancer
      therapies, but they are not effective in patients with ER negative and selective
      estrogen receptor modulator (SERM)-resistant tumors. Understanding the mechanisms
      of estrogen-stimulated proliferation may provide a route to design estrogen
      independent therapies that would be effective in these patients. In this study,
      metabolic flux analysis was used to determine the intracellular fluxes that are
      significantly affected by estradiol stimulation in MCF-7 breast cancer cells.
      Intracellular fluxes were calculated from nuclear magnetic resonance (NMR)
      generated isotope enrichment data and extracellular metabolite fluxes, using a
      specific flux analysis algorithm. The metabolic pathway model used by the
      algorithm includes glycolysis, the tricarboxylic acid cycle (TCA cycle), the
      pentose phosphate pathway, glutamine catabolism, pyruvate carboxylase, and malic
      enzyme. The pathway model also incorporates mitochondrial compartmentalization
      and reversible trans-mitochondrial membrane reactions to more accurately describe
      the role of mitochondria in cancer cell proliferation. Flux results indicate that
      estradiol significantly increases carbon flow through the pentose phosphate
      pathway and increases glutamine consumption. In addition, intra-mitochondrial
      malic enzyme was found to be inactive and the malate-aspartate shuttle (MAS) was
      only minimally active. The inactivity of these enzymes indicates that glutamine
      is not oxidized within mitochondria, but is consumed primarily to provide
      biosynthetic precursors. The excretion of glutamine carbons from the mitochondria
      has the secondary effect of limiting nicotinamide adenine dinucleotide (NADH)
      recycle, resulting in NADH buildup in the cytosol and the excretion of lactate.
      The observed dependence of breast cancer cells on pentose phosphate pathway
      activity and glutamine consumption for estradiol-stimulated biosynthesis suggests
      that these pathways may be targets for estrogen-independent breast cancer
      therapies.

PMID- 16904361
TI  - Physiochemical properties of digested sewage sludge with ultrasonic treatment.
AB  - We investigated the dewaterability and physiochemical properties of digested
      sludge after treatment with ultrasonic energy for the purpose of reducing sludge.
      The study involved laboratory experimentation under varying test conditions of
      treatment time, volume of sludge and ultrasonic energy, which combined can be
      denoted as specific supplied energy (E(v)). Results of the experiments show that
      particle size (dp(50), dp(10), U) of the ultrasonically treated sludge decreases
      due to the separation of sludge flocs. Capillary suction times (CSTs) decrease
      significantly, while turbidity, VDSs/VS and SCODs/TCOD increase with ultrasonic
      treatment. From these results, it was found that the ultrasonic treatment
      specified by the supplied energy (E(v)) can not only improve dewaterability but
      also reduce the volume and mass and change the chemical properties of sludge.

PMID- 16904362
TI  - Sonocrystallization: effect on lactose recovery and crystal habit.
AB  - Sonocrystallization is the use of power ultrasound to control the crystallization
      process, commonly used during the nucleation phase of crystallization. However,
      in the present study a different approach has been tried, in which the whole
      process of lactose crystallization from model reconstituted lactose solutions was
      completed rapidly with the aid of ultrasound, in the presence of 'ethanol' as an
      anti-solvent, at temperature of 30+/-2 degrees C (ambient temperature). The
      lactose recovery and crystal properties from sonicated samples were compared with
      non-sonicated samples. For optimization of sonocrystallization process for rapid
      lactose recovery, variations in the time of sonication, lactose concentration,
      protein concentration and pH were tried. A lactose recovery of 91.48% was
      obtained in 5 min of sonication time, from a reconstituted lactose solution
      (17.5% w/v, pH 4.2) as against 14.63% under only stirring. Lactose recovery
      decreased with lowering of pH from 4.2 to 2.8. The protein showed maximum
      influence on lactose recovery even at concentration of 0.2% w/v. A rapid process
      of crystallization gave a better uniformity in crystal size distribution of
      lactose samples.

PMID- 16904363
TI  - Sonochemical preparation of hydroxyapatite nanoparticles stabilized by
      glycosaminoglycans.
AB  - Stable hydroxyapatite (HAP) nanoparticles system was synthesized from
      Ca(H(2)PO(4))(2) aqueous solution and saturated Ca(OH)(2) aqueous solution by an
      improved precipitation method. This method was reformed through using ultrasound
      irradiation as assistant technology due to its unique chemical reaction effects
      and adding glycosaminoglycans (GAGs) as regulation additive due to its strong
      interaction with HAP. The products were characterized by Malvern Zetasizer 3000HS
      Analysis system, TEM and ED. The size distribution and zeta potential of HAP
      nanoparticles were influenced by the concentration of GAGs. With the GAGs
      concentration of 0.35g/L, the better excellent HAP nanoparticle system could be
      obtained with the number-averaged particle size of 22.2nm in 84.5% area and
      54.6nm in 15.5% area between 18.1nm and 117.4nm and the zeta potential of 
      60.9mV. In the presence of GAGs, the particle size and size distribution are
      little sensitive to the ultrasound irradiation (UI) time. With the increasing of
      UI time from 0.5h to 3h and 5h, the particle size increased a little and the
      crystallinity was improved. GAGs inhibited HAP crystal growth and stabilized HAP
      nanoparticles. Based on the TEM observation and size distribution determination
      of HAP nanoparticles, the possible formation mechanism of HAP nanoparticles
      stabilized by GAGs under UI was discussed.

PMID- 16904364
TI  - Stereo image matching for facial feature measurement to aid in fetal alcohol
      syndrome screening.
AB  - The facial phenotype associated with fetal alcohol syndrome is identified through
      the measurement of facial distances and their comparison to population norms. As
      an alternative to time-consuming direct manual measurements, stereo
      photogrammetry has been used to obtain the required facial measurements from
      stereo digital photographs. While stereo photogrammetric measurement is faster,
      it requires manual marking of relevant facial landmarks on digital images. We
      present an algorithm that automatically finds matched feature points on the
      second of a pair of stereo images, after manual marking of the first. Standard
      image processing tools are used for preprocessing. Matching is based on a simple
      exhaustive search in an image window, with the sum of squared differences of the
      pixel intensities in the two images as the objective function. Eye measurements,
      namely palpebral fissure length, interpupillary distance, inner canthal distance
      and outer canthal distance, as well as distances that can be used to approximate
      the circularity of the upper lip, were obtained using the manual method of
      marking both images, and the method of automatic marking of the second image.
      Comparison revealed mean differences less than 1mm.

PMID- 16904365
TI  - Combined topiramate and declorazepam therapy in a patient affected by essential
      tremor.

PMID- 16904366
TI  - Clinical efficacy of new antifungal agents.
AB  - Several new options are now available for treating serious fungal infections. All
      three echinocandin agents currently available have been shown in randomized,
      blinded clinical trials to be efficacious in treating candidemia and invasive
      candidiasis. By contrast, the demonstrated efficacy of the echinocandins for the
      treatment of invasive aspergillosis has been based on historically controlled
      salvage treatment trials in patients failing or intolerant of other therapies.
      The new triazole agents, voriconazole and posaconazole, have a broad spectrum of
      antifungal activity. Voriconazole has become the agent of choice for invasive
      aspergillosis. On the basis of compassionate treatment data, posaconazole appears
      to be effective for treatment of zygomycosis. These agents have also been shown
      to be effective in the treatment of non-Aspergillus mould infections, several of
      the endemic mycoses and serious Candida infections.

PMID- 16904367
TI  - Mobile information and communication in the hospital outpatient service.
AB  - OBJECTIVES: Most healthcare providers provide mobile service for their medical
      staff; however, few healthcare providers provide mobile service as part of their
      outpatient service. The mobile outpatient service system (MOSS) focuses on
      illness treatment, illness prevention and patient relation management for
      outpatient service users. Initiated in a local hospital in Taiwan, the MOSS pilot
      project was developed to improve outpatient service quality and pursue higher
      patient safety. METHOD: This study focuses on the development of the MOSS. The
      workflow, architecture and target users of the MOSS are delineated. In addition,
      there were two surveys conducted as part of this study. After a focus group of
      medical staff identified areas in which outpatient services might be improved by
      the MOSS, the first survey was administered to outpatients to confirm the focus
      group's intuitions. The second administration of the survey explored outpatient
      satisfaction after they used the MOSS service. RESULTS: With regard to outpatient
      attitudes, about 93% of participants agreed that the mobile outpatient service
      improved outpatient service quality. In the area of outpatient satisfaction,
      about 89% of participants indicated they were satisfied with the mobile
      outpatient service. DISCUSSION/CONCLUSION: Supported by our study finding, we
      propose that more diverse mobile outpatient services can be provided in the
      future.

PMID- 16904368
TI  - Inhibition of ATP binding to the carboxyl terminus of Kir6.2 by
      epoxyeicosatrienoic acids.
AB  - Epoxyeicosatrienoic acids (EETs), the cytochrome P450 metabolites of arachidonic
      acid (AA), are potent and stereospecific activators of cardiac ATP-sensitive
      K(+)(K(ATP)) channels. EETs activate K(ATP) channels by reducing channel
      sensitivity to ATP. In this study, we determined the direct effects of EETs on
      the binding of ATP to K(ATP) channel protein. A fluorescent ATP analog, 2,4,6
      trinitrophenyl (TNP)-ATP, which increases its fluorescence emission significantly
      upon binding with proteins, was used for binding studies with glutathione-S
      transferase (GST) Kir6.2 fusion proteins. TNP-ATP bound to GST fusion protein
      containing the C-terminus of Kir6.2 (GST-Kir6.2C), but not to the N-terminus of
      Kir6.2, or to GST alone. 11,12-EET (5 muM) did not change TNP-ATP binding K(D) to
      GST-Kir6.2C, but B(max) was reduced by half. The effect of 11,12-EET was dose
      dependent, and 8,9- and 14,15-EETs were as effective as 11,12-EET in inhibiting
      TNP-ATP binding to GST-Kir6.2C. AA and 11,12-dihydroxyeicosatrienoic acid (11,12
      DHET), the parent compound and metabolite of 11,12-EET, respectively, were not
      effective inhibitors of TNP-ATP binding to GST-Kir6.2C, whereas the methyl ester
      of 11,12-EET was. These findings suggest that the epoxide group in EETs is
      important for modulation of ATP binding to Kir6.2. We conclude that EETs bind to
      the C-terminus of K(ATP) channels, inhibiting binding of ATP to the channel.

PMID- 16904370
TI  - PhospholipaseA2: a key regulator of inflammatory signalling and a connector to
      fibrosis development in atherosclerosis.
AB  - Atherosclerosis is a progressive inflammatory disease that takes place in the
      intima of the arterial wall. It is characterized by activation of endothelial
      cells, proliferation of smooth muscle cells and macrophages, accumulation of
      lipoproteins, deposition of extracellular matrix components and enhanced
      lipolytic enzyme activity. Phospholipase A(2) (PLA(2)) has been postulated to
      play an important role in the inflammatory process of atherosclerosis, but its
      molecular mechanism is uncertain. The secretory PLA(2) is expressed at increased
      levels in an atherosclerotic plaque and may hydrolyze low-density lipoproteins
      (LDL). This action promotes the production of pro-inflammatory lipids such as
      lysophospholipids, unsaturated fatty acids and eicosanoids. The current review
      highlights recent findings on how LDL-derived lipid mediators, generated by
      sPLA_2 modification of LDL, regulate pro-inflammatory activation and
      intracellular signaling in macrophages. Moreover, the review discusses how PLA_2
      enzymes regulate signalling that promotes collagen accumulation and fibrotic
      plaque development. PLA_2 could therefore function as a connector between
      inflammation and fibrosis, the latter being an endpoint of chronic inflammation.

PMID- 16904369
TI  - New insights into the regulation of cardiolipin biosynthesis in yeast:
      implications for Barth syndrome.
AB  - Recent studies have revealed an array of novel regulatory mechanisms involved in
      the biosynthesis and metabolism of the phospholipid cardiolipin (CL), the
      signature lipid of mitochondria. CL plays an important role in cellular and
      mitochondrial function due in part to its association with a large number of
      mitochondrial proteins, including many which are unable to function optimally in
      the absence of CL. New insights into the complexity of regulation of CL provide
      further evidence of its importance in mitochondrial and cellular function. The
      biosynthesis of CL in yeast occurs via three enzymatic steps localized in the
      mitochondrial inner membrane. Regulation of this process by general phospholipid
      cross-pathway control and factors affecting mitochondrial development has been
      previously established. In this review, novel regulatory mechanisms that control
      CL biosynthesis are discussed. A unique form of inositol-mediated regulation has
      been identified in the CL biosynthetic pathway, independent of the INO2-INO4-OPI1
      regulatory circuit that controls general phospholipid biosynthesis. Inositol
      leads to decreased activity of phosphatidylglycerolphosphate (PGP) synthase,
      which catalyzes the committed step of CL synthesis. Reduced enzymatic activity
      does not result from alteration of expression of the structural gene, but is
      instead due to increased phosphorylation of the enzyme. This is the first
      demonstration of phosphorylation in response to inositol and may have significant
      implications in understanding the role of inositol in other cellular regulatory
      pathways. Additionally, synthesis of CL has been shown to be dependent on
      mitochondrial pH, coordinately controlled with synthesis of mitochondrial
      phosphatidylethanolamine (PE), and may be regulated by mitochondrial DNA absence
      sensitive factor (MIDAS). Further characterization of these regulatory mechanisms
      holds great potential for the identification of novel functions of CL in
      mitochondrial and cellular processes.

PMID- 16904371
TI  - The oxidized phospholipids POVPC and PGPC inhibit growth and induce apoptosis in
      vascular smooth muscle cells.
AB  - Oxidized phospholipids, including 1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3
      phosphocholine (POVPC) and 1-palmitoyl-2-glutaroyl-sn-glycero-3-phosphocholine
      (PGPC) are typically present in oxidatively modified low density lipoprotein
      (oxLDL) and have been found in atherosclerotic lesions. These compounds are
      gaining increasing importance as inducers of different cellular responses like
      inflammation, proliferation, or cell death. The aim of this study was to elicit
      the type and outcome of the cellular response of vascular smooth muscle cells
      (VSMC) upon treatment with POVPC and PGPC. Both oxidized phospholipids led to
      inhibition of cell proliferation and showed cytotoxic effects in VSMC. Several
      morphological criteria, the presence of typical DNA fragments, and a
      phosphatidylserine shift towards the outer leaflet of the cell membrane revealed
      that apoptosis was the predominant mode of cell death. In all experiments, POVPC
      was found to be a more potent inducer of apoptosis than PGPC. Interestingly, in
      the presence of high levels of serum in the growth media the proapoptotic but not
      the antiproliferative effects of both oxidized phospholipids were abolished.
      Thus, we conclude that under low serum conditions both intact POVPC and PGPC are
      proapoptotic mediators. Under high serum conditions, these lipids are hydrolyzed
      and the resultant lipid mixture containing the degradation products is no longer
      apoptotic but antiproliferative. Thus, the direct and indirect effects of POVPC
      and PGPC on cell viability may account for the detrimental actions of oxLDL on
      VSMC.

PMID- 16904372
TI  - Development of polymer-based sensors for integration into a wireless data
      acquisition system suitable for monitoring environmental and physiological
      processes.
AB  - In this work, the pressure sensing properties of polyethylene (PE) and
      polyvinylidene fluoride (PVDF) polymer films were evaluated by integrating them
      with a wireless data acquisition system. Each device was connected to an
      integrated interface circuit, which includes a capacitance to frequency converter
      (C/F) and an internal voltage regulator to suppress supply voltage fluctuations
      on the transponder side. The system was tested under hydrostatic pressures
      ranging from 0 to 17 kPa. Results show PE to be the more sensitive to pressure
      changes, indicating that it is useful for the accurate measurement of pressure
      over a small range. On the other hand PVDF devices could be used for measurement
      over a wider range and should be considered due to the low hysteresis and good
      repeatability displayed during testing. It is thought that this arrangement could
      form the basis of a cost-effective wireless monitoring system for the evaluation
      of environmental or physiological processes.

PMID- 16904373
TI  - Supplementation with sterols improves food quality of a ciliate for Daphnia
      magna.
AB  - Experimental results provide evidence that trophic interactions between ciliates
      and Daphnia are constrained by the comparatively low food quality of ciliates.
      The dietary sterol content is a crucial factor in determining food quality for
      Daphnia. Ciliates, however, presumably do not synthesize sterols de novo. We
      hypothesized that ciliates are nutritionally inadequate because of their lack of
      sterols and tested this hypothesis in growth experiments with Daphnia magna and
      the ciliate Colpidium campylum. The lipid content of the ciliate was altered by
      allowing them to feed on fluorescently labeled albumin beads supplemented with
      different sterols. Ciliates that preyed upon a sterol-free diet (bacteria) did
      not contain any sterols, and growth of D. magna on these ciliates was poor.
      Supplementation of the ciliates' food source with different sterols led to the
      incorporation of the supplemented sterols into the ciliates' cells and to
      enhanced somatic growth of D. magna. Sterol limitation was thereby identified as
      the major constraint of ciliate food quality for Daphnia. Furthermore, by
      supplementation of sterols unsuitable for supporting Daphnia growth, we provide
      evidence that ciliates as intermediary grazers biochemically upgrade unsuitable
      dietary sterols to sterols appropriate to meet the physiological demands of
      Daphnia.

PMID- 16904374
TI  - EFL GTPase in cryptomonads and the distribution of EFL and EF-1alpha in
      chromalveolates.
AB  - EFL (EF-like protein) is a member of the GTPase superfamily that includes several
      translation factors. Because it has only been found in a few eukaryotic lineages
      and its presence correlates with the absence of the related core translation
      factor EF-1alpha, its distribution is hypothesized to be the result of lateral
      gene transfer and replacement of EF-1alpha. In one supergroup of eukaryotes, the
      chromalveolates, two major lineages were found to contain EFL (dinoflagellates
      and haptophytes), while the others encode EF-1alpha (apicomplexans, ciliates,
      heterokonts and cryptomonads). For each of these groups, this distribution was
      deduced from whole genome sequence or expressed sequence tag (EST) data from
      several species, with the exception of cryptomonads from which only a single EF
      1alpha PCR product from one species was known. By sequencing ESTs from two
      cryptomonads, Guillardia theta and Rhodomonas salina, and searching for all
      GTPase translation factors, we revealed that EFL is present in both species, but,
      contrary to expectations, we found EF-1alpha in neither. On balance, we suggest
      the previously reported EF-1alpha from Rhodomonas salina is likely an artefact of
      contamination. We also identified EFL in EST data from two members of the
      dinoflagellate lineage, Karlodinium micrum and Oxyrrhis marina, and from an
      ongoing genomic sequence project from a third, Perkinsus marinus. Karlodinium
      micrum is a symbiotic pairing of two lineages that would have both had EFL (a
      dinoflagellate and a haptophyte), but only the dinoflagellate gene remains.
      Oxyrrhis marina and Perkinsus marinus are early diverging sister-groups to
      dinoflagellates, and together show that EFL originated early in this lineage.
      Phylogenetic analysis confirmed that these genes are all EFL homologues, and
      showed that cryptomonad genes are not detectably related to EFL from other
      chromalveolates, which collectively form several distinct groups. The known
      distribution of EFL now includes a third group of chromalveolates, cryptomonads.
      Of the six major subgroups of chromalveolates, EFL is found in half and EF-1alpha
      in the other half, and none as yet unambiguously possess both genes. Phylogenetic
      analysis indicates EFL likely arose early within each subgroup where it is found,
      but suggests it may have originated multiple times within chromalveolates as a
      whole.

PMID- 16904375
TI  - Peptide deformylase as an antibacterial target: a critical assessment.
AB  - Peptide deformylase (PDF) is among the few antibacterial targets against which
      novel synthetic inhibitors derived from rationally designed, mechanism-based
      libraries have progressed into clinical trials. Nearly two decades of
      investigation led to this milestone; however, increased understanding of
      resistance to these compounds and recent evidence of catalytically active human
      mitochondrial PDF impact the perception of PDF as an antibacterial target. There
      are also many unanswered questions concerning the mechanism of action of PDF
      inhibitors and the necessity of the formylation/deformylation cycle in bacteria.
      Nevertheless, the experience gained from research on PDF serves as perhaps the
      best current illustration of the risks and possibilities associated with novel
      target-based antibiotic discovery.

PMID- 16904376
TI  - Novel targets for tuberculosis drug discovery.
AB  - Since the determination of the Mycobacterium tuberculosis genome sequence,
      various groups have used the genomic information to identify and validate targets
      as the basis for the development of new anti-tuberculosis agents. Validation
      might include many components: demonstration of the biochemical activity of the
      enzyme, determination of its crystal structure in complex with an inhibitor or a
      substrate, confirmation of essentiality, and the identification of potent growth
      inhibitors either in vitro or in an infection model. If novel target validation
      and subsequent inhibition are matched by an improved understanding of disease
      biology, then new antibiotics could have the potential to shorten the duration of
      therapy, prevent resistance development and eliminate latent disease.

PMID- 16904377
TI  - Clinical experience with recently approved antibiotics.
AB  - The advent of vancomycin-resistant enterococci in the 1990s and the threat posed
      by vancomycin resistance in Staphylococcus aureus led to the development of
      several new antimicrobial agents active against these pathogens.
      Quinupristin/dalfopristin was the first such drug to be commercially available
      but adverse effects have meant that the drug is now rarely used. Linezolid, the
      first antimicrobial of the oxazolidinone class, has met with more widespread use
      and has both an intravenous and an oral formulation. Daptomycin is a lipopeptide
      antimicrobial that is rapidly bactericidal against S. aureus. It is effective in
      the therapy of S. aureus bloodstream infections but is inactivated by pulmonary
      surfactant, making it of no use in the therapy of pneumonia. Tigecycline, by
      contrast, is bacteriostatic against most pathogens but has a broad spectrum of
      antimicrobial activity and has enhanced penetration into many tissues. Other new
      antibiotics (dalbavancin, telavancin, ceftobiprole and doripenem) are currently
      under clinical development and hold promise for widespread clinical use in the
      next decade.

PMID- 16904378
TI  - Toxoplasma gondii and subversion of the immune system.
AB  - Toxoplasma gondii is an intracellular obligate parasite that enters the host via
      the gastrointestinal tract. The parasite is able to evade or subvert the immune
      response of its host via various mechanisms. Here, we discuss a recent in vitro
      study by Eric Denkers and colleagues that focused on the modulation of gene
      transcription of host macrophages stimulated by lipopolysaccharide (LPS)
      following infection with T. gondii. The parasite was able to block the response
      of macrophages to LPS, a major immunostimulatory component of Gram negative
      bacteria, thus possibly avoiding the hyperinflammatory response of the host to
      gut microflora, among which Gram negative bacteria are abundant.

PMID- 16904380
TI  - The transferrin receptor part I: Biology and targeting with cytotoxic antibodies
      for the treatment of cancer.
AB  - The transferrin receptor (TfR) is a cell membrane-associated glycoprotein
      involved in the cellular uptake of iron and in the regulation of cell growth.
      Iron uptake occurs via the internalization of iron-loaded transferrin (Tf)
      mediated by the interaction with the TfR. In addition, the TfR may also contain
      other growth regulatory properties in certain normal and malignant cells. The
      elevated levels of TfR in malignancies, its relevance in cancer, and the
      extracellular accessibility of this molecule make it an excellent antigen for the
      treatment of cancer using antibodies. The TfR can be targeted by monoclonal
      antibodies specific for the extracellular domain of the receptor. In this review,
      we summarize advancements in the basic physiology of the TfR including structure,
      function, and expression. We also discuss the efficacy of targeting the TfR using
      cytotoxic antibodies that inhibit cell growth and/or induce apoptosis in targeted
      malignant cells.

PMID- 16904381
TI  - IL-10 gene modified dendritic cells induced antigen-specific tolerance in
      experimental autoimmune myocarditis.
AB  - Experimental autoimmune myocarditis (EAM) in rats is a T-cell-mediated disorder,
      and the involvement of Th1/Th2 unbalance has been demonstrated. The induction of
      antigen-specific tolerance is critical for the treatment of EAM and maintenance
      of immune tolerance. IL-10 is a pleiotrophic immunomodulatory cytokine that
      functions at different levels of the immune response, so it has emerged as a
      promising therapeutic factor for the treatment of autoimmune/inflammatory
      diseases. This study was designed to explore the effects of IL-10 gene modified
      bone-marrow-derived immature dendritic cells (iDCs) on the in vitro and in vivo
      immune response to cardiac myosin in EAM. EAM was induced using the classic
      methods of cardiac myosin immunization on day 0 and day 7. 2 x 10(6)/per rat
      mature DC (mDC), immature DC (iDC), pcDNA3 transfected iDC, pcDNA3-IL-10
      transfected iDC or PBS were injected intravenously for treatment 5 days after the
      first immunization. On day 21, transthoracic echocardiogram and HE staining were
      performed to detect the cardiac function and myocardial inflammation. Th1/Th2
      cytokines were detected by ELISA and MHC-II molecules, costimulatory molecules
      were identified by flow cytometry. In vitro T lymphocyte proliferation assay and
      adoptive transfer of DCs were performed to determine the antigen-specific
      tolerance induced by IL-10 gene modified iDCs. IL-10 gene modified iDC-treated
      EAM rats showed improved cardiac function and reduced infiltration of
      inflammatory cell into myocardium. Serum cytokines data indicated lower Th1 while
      higher Th2-type responses were induced in the pcDNA3-IL-10-iDC-treated group,
      suggesting a Th2 polarization. Moreover, IL-10 gene modified iDCs down-regulated
      MHC-II and costimulatory molecules on the surface of splenocytes and inhibited
      the antigen-specific immunological responses towards cardiac myosin. Adoptive
      transfer of IL-10 producing DCs prevented EAM induction. IL-10 gene modified iDCs
      ameliorates EAM histopathologically and functionally. The underlying mechanisms
      may be related to the IL-10 induced Th2 polarization and down-regulation of MHC
      II molecules and costimulatory molecules expression.

PMID- 16904382
TI  - The influence of Zn on signaling pathways and attachment of Mytilus
      galloprovincialis haemocytes to extracellular matrix proteins.
AB  - The present study investigates the cytotoxic mechanisms induced by zinc (Zn) in
      haemocytes of mussel Mytilus galloprovincialis. Haemocytes play a key role in the
      immune defence of mussels. Micromolar concentration of Zn (50 microM) play an
      important role in the elevation of pHi and increase in Na+ influx in haemocytes.
      The observed effects were inhibited by the Na+/H+ exchanger (NHE) inhibitor,
      ethyl-N-isopropyl-amiloride (EIPA). Furthermore, our results showed that Zn
      caused an increase in O(-)(2) production that was reversed after NHE inhibition.
      Phorbol ester (PMA) caused a significant rise both in pHi and Na+ influx as well
      as in O(-)(2) production. These effects were reversed by calphostin C. Our
      results indicated that Zn also enhanced haemocyte attachment to both BSA and
      laminin which was reversed by EIPA and calphostin C. The enhancement of
      haemocytes attachment to both BSA and laminin after Zn suggests that it is likely
      to play a signal role in cytoskeleton-dependent process of cell growth and
      migration in mussel M. galloprovincialis haemocytes. We conclude that Zn induces
      a signaling pathway with the involvement of NHE, PKC, O(-)(2) and alpha1- and
      beta-adrenergic receptors.

PMID- 16904383
TI  - Comparative study of DNA damage, cell cycle and apoptosis in human K562 and CCRF
      CEM leukemia cells: role of BCR/ABL in therapeutic resistance.
AB  - The Philadelphia translocation t(9;22) resulting in the bcr/abl fusion gene is
      the pathogenic principle of almost 95% of human chronic myelogenous leukemia
      (CML). Imatinib mesylate (STI571) is a specific inhibitor of the BCR/ABL fusion
      tyrosine kinase that exhibits potent antileukemic effects in CML. BCR/ABL
      positive K562 and -negative CCRF-CEM human leukemia cells were investigated. MTT
      survival assay and clonogenic test of the cell proliferation ability were used to
      estimate resistance against idarubicin. DNA damage after cell treatment with the
      drug at the concentrations from 0.001 to 3 microM with or without STI571 pre
      treatment were examined by the alkaline comet assay. We found that the level of
      DNA damages was lower in K562 cells after STI571 pre-treatment. It is suggested
      that BCR/ABL activity may promote genomic instability, moreover K562 cells were
      found to be resistant to the drug treatment. Further, we provided evidence of
      apoptosis inhibition in BCR/ABL-positive cells using caspase-3 activity
      colorimetric assay and DAPI nuclear staining for chromatin condensation. We
      suggest that these processes associated with cell cycle arrest in G2/M checkpoint
      detected in K562 BCR/ABL-positive compared to CCRF-CEM cells without BCR/ABL
      expression might promote clone selection resistance to drug treatment.

PMID- 16904384
TI  - Cognitive factors influencing perceptions of clinical documentation tools.
AB  - Identifying healthcare providers' perceptions of clinical documentation methods
      can inform the design of computer-based documentation tools. The authors
      investigated the cognitive factors underlying such perceptions by performing a
      qualitative analysis that included open-ended in-depth interviews of a
      convenience sample of healthcare providers who use a variety of documentation
      methods. A total of 16 providers participated in the study; subjects included
      physicians and nurse practitioners from medical and surgical specialties who used
      paper- and computer-based documentation tools. Based on interview data, authors
      identified five factors that influenced satisfaction with clinical documentation
      tools: document system time efficiency, availability, expressivity, structure,
      and quality. These factors, if validated by subsequent investigations, can be
      used to develop a formal conceptual model of providers' perceptions of their
      satisfaction with various documentation systems.

PMID- 16904385
TI  - The expression of Usp42 during embryogenesis and spermatogenesis in mouse.
AB  - Mouse Usp42, a novel ubiquitin specific protease gene, was isolated from mouse
      embryonic stem cells. It consists of 1,324 amino acids with a predicted molecular
      weight of 146kDa and contains the conserved Cys, Asp (I), His and Asn/Asp (II)
      domains defined as one of characteristics for deubiquitinating enzymes. RT-PCR
      analysis showed that the Usp42 transcript is expressed in NIH3T3 cells, B- and T
      lymphocytes, and L1210 cells. Northern blot analysis revealed that Usp42 is
      expressed mainly in brain, lung, thymus and testis, and at mouse E10.5 the most
      during embryonic development. Usp42 expression rises from 2 weeks after birth to
      round-spermatid stage and decreases from condensing-spermatid stage during
      spermatogenesis. Deubiquitinating enzyme assays demonstrated that Usp42 can
      cleave ubiquitin from ubiquitinated substrates in vitro and in vivo. Taken all
      together, it is suggested that Usp42 is one of typical deubiquitinating enzymes,
      which may play an important role in mouse embryogenesis and spermatogenesis.

PMID- 16904386
TI  - Electrooxidation of dissolved dsDNA backed by in situ UV-Vis spectroscopy.
AB  - The electrooxidation of double-stranded DNA (dsDNA) from calf thymus was carried
      by using cyclic voltammetry. A glassy carbon disk-, a platinum disk-, a platinum
      mesh- and a carbon vapor-deposited platinum mesh electrodes were used. It is
      shown that the appropriate chemical and biological (steam treatment) purification
      of the complete cell allows, for the graphite electrode, formation of a wide
      anodic dsDNA signal with two visible anodic peaks. There was no necessity of
      preaccumulation of dsDNA on the electrode surface and of use of mediators to get
      well defined voltammetric signals. These peaks apparently reflect
      electrooxidation of the DNA's guanine and adenine. The spectrophotometric data
      obtained during the electrooxidation indicate that the absorbance increases with
      an increase in potential and electrooxidation current of dsDNA. However, the
      absorption band maximum either does or does not change its position depending on
      the mesh material. This different spectroscopic behavior may mean that the
      changes in the dsDNA structure upon electrooxidation are different in the case of
      Pt and C electrodes.

PMID- 16904387
TI  - Replication arrest-stimulated recombination: Dependence on the RecA paralog,
      RadA/Sms and translesion polymerase, DinB.
AB  - Difficulties in replication can lead to breakage of the fork. Recombinational
      reactions restore the integrity of the fork through strand-invasion of the broken
      chromosome with its sister. If this occurs in the context of repeated DNA
      sequences, genetic rearrangements can result. We have proposed that this process
      accounts for stimulation of chromosomal rearrangements by mutations in
      Escherichia coli's replicative DNA helicase, DnaB. At its permissive temperature
      for growth, a dnaB107 mutant is a 1000-fold more likely to experience a deletion
      of a 787bp tandem repeated segment inserted in the E. coli chromosome than is a
      wild-type strain. We have previously shown that enhanced deletion in a dnaB107
      strain is reduced in recA, recB and recG102 (formerly known as radC102)
      derivatives. Here I show that this enhanced recombination is dependent on other
      factors: the RuvA Holliday junction helicase, the RecJ single-strand DNA
      exonuclease, the RadA/Sms RecA-paralog protein of unknown function and,
      surprisingly, the DinB translesion polymerase. The requirement for these factors
      in DnaB-stimulated rearrangements is much greater than that observed for
      recombinational events such as P1 transduction. This may be because strand
      invasion into the repeats limits the extent of heteroduplex DNA that can be
      formed in the initial stage of recombination. I propose that RadA, RecG and RuvAB
      are critically required to stabilize the strand-invasion intermediate and that
      DinB polymerase extends the invading 3' strand to aid in re-initiation. The role
      of DinB in bacteria may be analogous to translesion DNA polymerase eta in
      eukaryotes, recently shown to aid recombination.

PMID- 16904388
TI  - Adherence of adult cystic fibrosis patients with airway clearance and exercise
      regimens.
AB  - BACKGROUND: Regular airway clearance and exercise form an important part of the
      physiotherapy management of patients with cystic fibrosis (CF). Previous research
      has found that adherence of these patients with physiotherapy regimens is
      variable and influenced by factors such as sex and disease severity. To date, the
      adherence of Australian patients with CF has not been investigated. The aim of
      this study was to measure the adherence of a sample of Australian adult patients
      with CF and to ascertain factors that improved or decreased their adherence with
      physiotherapy. METHODS: Patients attending an Australian CF Unit were surveyed by
      an independent physiotherapist using a questionnaire based on the Manchester
      Cystic Fibrosis Compliance Questionnaire. RESULTS: Fifty seven of the 84 patients
      registered with the Unit (67.9% response rate) completed the survey. Over the
      previous six months, 96.5% of patients reported doing some form of airway
      clearance, with 70.2% doing this daily or only occasionally missing one or two
      days. Regular exercise was performed by 91.2% of patients when well, with 77.8%
      also exercising regularly when unwell. The most common reasons for non-adherence
      with airway clearance regimens were being too busy and not being bothered. Being
      too busy and too tired were the most frequent reasons for decreased adherence
      with exercise. Frequency of performing airway clearance regimens significantly
      improved when patients felt unwell. Adherence with exercise regimens was
      significantly higher in those who worked or studied full time. CONCLUSION:
      Overall, the levels of adherence with physiotherapy regimens found in this study
      were considered to be satisfactory and higher than those previously reported in
      the literature, with time related factors being the most commonly reported
      reasons for decreasing adherence.

PMID- 16904390
TI  - Multidrug ABC transporters from bacteria to man: an emerging hypothesis for the
      universality of molecular mechanism and function.

PMID- 16904389
TI  - Intermittent treatment with parathyroid hormone (PTH) as well as a non-peptide
      small molecule agonist of the PTH1 receptor inhibits adipocyte differentiation in
      human bone marrow stromal cells.
AB  - Whereas continuous PTH infusion increases bone resorption and bone loss,
      intermittent PTH treatment stimulates bone formation, in part, via reactivation
      of quiescent bone surfaces and reducing osteoblast apoptosis. We investigated the
      possibility that intermittent and continuous PTH treatment also differentially
      regulates osteogenic and adipocytic lineage commitment of bone marrow stromal
      progenitor/mesenchymal stem cells (MSC). The MSC were cultured under mildly
      adipogenic conditions in medium supplemented with dexamethasone, insulin,
      isobutyl-methylxanthine and troglitazone (DIIT), and treated with 50 nM human
      PTH(1-34) for either 1 h/day or continuously (PTH replenished every 48 h). After
      6 days, cells treated with PTH for 1 h/day retained their normal fibroblastic
      appearance whereas those treated continuously adopted a polygonal, irregular
      morphology. After 12-18 days numerous lipid vacuole and oil red O-positive
      adipocytes had developed in cultures treated with DIIT alone, or with DIIT and
      continuous PTH. In contrast, adipocyte number was reduced and alkaline
      phosphatase staining increased in the cultures treated with DIIT and 1 h/day PTH,
      indicating suppression of adipogenesis and possible promotion of early
      osteoblastic differentiation. Furthermore, intermittent but not continuous PTH
      treatment suppressed markers of differentiated adipocytes such as mRNA expression
      of lipoprotein lipase and PPARgamma as well as glycerol 3-phosphate dehydrogenase
      activity. All of these effects of intermittent PTH were also produced by a 1
      h/day treatment with AH3960 (30 microM), a small molecule, non-peptide agonist of
      the PTH1 receptor. AH3960, like PTH, activates both the cAMP and calcium
      signaling pathways. Treatment with the adenylyl cyclase activator forskolin for 1
      h/day, mimicked the anti-adipogenic effect of intermittent PTH, whereas
      pretreatment with the protein kinase-A inhibitor H89 prior to intermittent PTH
      resulted in almost complete conversion to adipocytes. In contrast, the MAP kinase
      inhibitor PD 98059 failed to prevent the anti-adipocytic effect of intermittent
      PTH, suggesting that the inhibitory effect of PTH on adipocyte differentiation is
      predominantly cAMP-dependent. These results demonstrate a differential effect of
      PTH1 receptor agonists on the adipocytic commitment and differentiation of adult
      human bone marrow mesenchymal stem cells. This response may represent an
      additional mechanism that contributes to the overall bone anabolic action of
      intermittent PTH.

PMID- 16904391
TI  - Different cell thresholds for commitment to death: a link between carcinogenesis
      and drug resistance.
AB  - All classes of anticancer drugs induce apoptosis both in vitro and in vivo.
      Because apoptosis is a genetically controlled process, this implies that death
      induced by these drugs is genetically controlled at loci different from those
      involved in their direct mechanisms of action. This is stimulus-response
      coupling; the drugs provide the stimulus through imposition of cell damage.
      Failure to couple damage to the response of death characterizes a pleiotropic
      form of drug resistance. Different cell phenotypes have different thresholds for
      the engagement of death, which need not only be by apoptosis. The balance of
      expression of genes which promote or suppress active cell death defines these
      thresholds.

PMID- 16904392
TI  - Neovascularization: the Achilles' heel of tumors?

PMID- 16904393
TI  - Antifungal combination therapy: where we stand.
AB  - Amphotericin B has been used in combination, simultaneously or sequentially, with
      fluconazole and itraconazole. However, there are no data from clinical trials to
      suggest the most appropriate use of these drug combinations. In vitro work has
      consistently described antagonism of polyenes and azoles, but new work suggests
      that hydrophilic azoles (e.g. fluconazole) with amphotericin B may not result in
      antagonistic effects, whereas lipophilic azoles (e.g. ketoconazole, itraconazole)
      antagonize the antifungal effects of amphotericin B. Experimental studies in
      animals with invasive candidiasis show that fluconazole and amphotericin B are
      not antagonistic and may be additive in their effects. In contrast, itraconazole
      and amphotericin B are antagonistic in this same murine candidiasis model. In
      animals infected with Aspergillus, itraconazole plus amphotericin B seem to be
      antagonistic when used simultaneously and possibly when used sequentially.
      Nevertheless, initial therapy with amphotericin B followed by itraconazole in
      patients with aspergillosis is a common clinical strategy. Recent data and
      concepts concerning the combined use of available antifungal drugs are discussed
      in this paper.

PMID- 16904394
TI  - The role of outer membrane and efflux pumps in the resistance of gram-negative
      bacteria. Can we improve drug access?
AB  - Many antibiotics inhibit gram-negative bacteria less effectively than gram
      positive bacteria, because the outer membrane permeability barrier allows only a
      slow influx of drugs, and the small number of drug molecules that traversed the
      outer membrane are efficiently inactivated or pumped out back into the medium,
      the last-mentioned process often catalyzed by widely distributed multidrug efflux
      pumps. Paradoxically, drugs of advanced design that are not inactivated
      enzymatically, such as beta-lactamase-stable lactams and fluoroquinolones, tend
      to select for more resistant mutants which overexpress these pumps. The drug
      hypersensitive phenotype of efflux-deficient mutants suggests that inhibition of
      the pumps may be a good way not only to combat resistance of this type, but also
      to make 'intrinsically' resistant gram-negative bacteria susceptible to a wide
      range of drugs. Alternatively, the outer membrane can be permeabilized by
      cationic peptides, thereby sensitizing bacteria especially to lipophilic
      antibiotics.

PMID- 16904395
TI  - Apoptin-induced apoptosis: potential for antitumor therapy.
AB  - Cytotoxic anticancer agents often exert their effect by inducing apoptosis. Many
      tumors, however, are resistant to chemotherapy. This is due to lack of expression
      of certain genes essential in mediating the apoptotic signal, such as p53, or to
      over-expression of apoptosis inhibitors, such as bcl-2 or bcr-abl. Apoptin, a
      small protein derived from an avian virus, induces a p53-independent, bcr-abl
      insensitive, and bcl-2-stimulated apoptosis in various human tumor cells.
      Interestingly, apoptin does not induce apoptosis in normal diploid cells. These
      features make apoptin a promising antitumor agent. Strategies for anti-cancer
      therapy based on viral vectors expressing apoptin are under development.

PMID- 16904396
TI  - HIV resistance to antiviral drugs: public health implications.
AB  - The widespread occurrence of HIV strains resistant to antiviral drugs has given
      rise to a number of important concerns distinct from the obvious question of the
      relationship between drug resistance and treatment failure. A major issue is the
      extent to which drug-resistant viruses may be transmitted in primary infection
      via sexual or intravenous routes and how this relates to the relative fitness of
      such strains. It is also important to understand the potential role of effective
      antiviral therapy in the decrease of viral burden in both blood and sexual
      secretions, and the extent to which this may be compromised in individuals
      harboring resistant viruses. A related subject is the important role of patient
      adherence to antiviral therapy in achieving sustained reduction in viral load and
      preventing the emergence of drug resistance. These linked topics are tied to the
      central role of antiviral agents in the selection of mutant forms that can attain
      a replication advantage in the presence of drug.

PMID- 16904397
TI  - Antibiotic resistance in gram-negative bacteria: the role of gene cassettes and
      integrons.
AB  - Resistance of gram-negative organisms to antibiotics such as beta-lactams,
      aminoglycosides, trimethoprim and chloramphenicol is caused by many different
      acquired genes, and a substantial proportion of these are part of small mobile
      elements known as gene cassettes. A gene cassette consists of the gene and a
      downstream sequence, known as a 59-base element (59-be), that acts as a specific
      recombination site. Gene cassettes can move into or out of a specific receptor
      site (attl site) in a companion element called an integron, and integration or
      excision of the cassettes is catalysed by a site-specific recombinase (Intl) that
      is encoded by the integron. At present count there are 40 different cassette
      associated resistance genes and three distinct classes of integron, each encoding
      a distinct Intl integrase. The same cassettes are found in all three classes of
      integron, indicating that cassettes can move freely between different integrons.
      Integrons belonging to class I often contain a further antibiotic resistance
      gene, sull, conferring resistance to sulphonamides. The sull gene is found in a
      conserved region (3'-CS) that is not present in all members of this class. Class
      I integrons of the sull type are most prevalent in clinical isolates and have
      been found in many different organisms. Even though most of them are defective
      transposon derivatives, having lost at least one of the transposition genes, they
      are none the less translocatable and consequently found in many different
      locations. The transposon Tn7 is the best known representative of class 2
      integrons, and Tn7 and relatives are also found in many different species.

PMID- 16904398
TI  - The influence of glutathione metabolism on multidrug resistance in MRP
      overexpressing cells.
AB  - The multidrug resistance (+associated) protein (MRP) is one of two ATP-dependent
      transport molecules which have been shown to be a cause of multidrug resistance
      in mammalian cells. The protein is ubiquitously expressed in human tissues and in
      a range of tumor types. In addition to a range of neutral or cationic cytotoxic
      drugs, MRP also transports heavy metals and organic anions including glutathione
      (GSH)-conjugates and glucuronate conjugates. In cells depleted of GSH, the
      activity of MRP towards cationic drugs is abrogated whereas activity towards
      organic anions is preserved. Possible mechanisms involved in this differential
      action and strategies for its exploitation in clinical chemotherapy are
      discussed.

PMID- 16904399
TI  - Mechanisms of isoniazid resistance in Mycobacterium tuberculosis.
AB  - Isoniazid (INH) is a widely used front-line antituberculous agent with
      bacteriocidal activity at concentrations as low as 150 nM against Mycobacterium
      tuberculosis. INH is a prodrug and requires activation by an endogenous
      mycobacterial enzyme, the catalase-peroxidase KatG, before exerting toxic effects
      on cellular targets. Resistance to INH develops primarily through failure to
      activate the prodrug due to point mutations in the katG gene. In addition to
      mutations in katG, mutations in several other loci, such as the
      alkylhydroperoxidase AhpC and the enoylreductase InhA, may contribute to INH
      resistance. Although these markers can be used to accurately predict clinical INH
      resistance in a large number of cases, the molecular mechanisms involved remain
      largely speculative and incomplete.

PMID- 16904400
TI  - Vancomycin resistance in staphylococci.
AB  - Recent emergence of vancomycin resistance in methicillin-resistant Staphylococcus
      aureus (VRSA) has posed a new threat to hospital infection control and antibiotic
      chemotherapy. Relatively low-level resistance of VRSA compared to that of
      vancomycin-resistant enterococci (VRE), and prevalence of S. aureus clinical
      strains heterogeneously resistant to vancomycin (hetero-VRSA), challenge the
      value of routine antibiotic susceptibility tests as a tool for the prediction of
      clinical efficacy of vancomycin therapy. This review summarizes the history of
      emergence of glycopeptide resistance in staphylococci and considers the mechanism
      of resistance in these organisms.

PMID- 16904403
TI  - Overuse of antibiotics for acute respiratory illnesses and the epidemic of
      penicillin-resistant Streptococcus pneumoniae.

PMID- 16904404
TI  - beta-Lactamase induction and cell wall recycling in gram-negative bacteria.
AB  - beta-Lactams with the ability to induce beta-lactamase in gram-negative bacteria
      bind to essential penicillin-binding proteins (PBPs) after entering the
      periplasmic space. This leads to inactivation of transpeptidase activities and
      thereby a decrease in the number of peptide cross-links, allowing further
      degradation of murein by soluble lytic transglycosylases. If all DD
      carboxypeptidases (PBP 4, 5, 6a and 6b) are inhibited as well, the degradation
      product aD-pentapeptide (N-acetylglucosaminyl-1,6-anhydro-N-acetylmuramyl-L
      alanyl-D-glutamyl-meso-diaminopimelic-acid-D-alanyl-D- alanine) accumulates,
      which is the case with inducing beta-lactams such as imipenem. These molecules in
      addition to tri- and tetrapeptides (N-acetylglucosaminyl-1,6-anhydro-N
      acetylmuramyl-L-alanyl-D-glutamyl-meso-diaminopimelic-acid-[D-alanine]) which are
      the usual degradation products of peptidoglycan, are released into the cytoplasm
      and displace the UDP-pentapeptide (UDP-N-acetylmuramyl-L-alanyl-D-glutamyl-meso
      diaminopimelic-acid-D-alanyl-D-alanine) from the DNA-binding protein AmpR,
      converting it into an activator of AmpC beta-lactamase expression.

PMID- 16904405
TI  - Bacterial energetics and antimicrobial resistance.
AB  - Defining resistance to antimicrobics with specific terms is very useful as the
      precise mechanisms often lead to better susceptibility testing and improved
      treatment of bacterial infections. When one can characterize a class of
      phenotypic resistant organisms as electron transport variants, this has value in
      that it provides information about the basis for resistance and removes them from
      the non-specific categorization as phenotypically resistant. Studies of bacterial
      small colony variants (SCVs) has provided new insights into antimicrobial
      resistance as well as the connection between expression of virulence factors and
      energy metabolism. It also provides a framework for further studies which link
      antibiotic resistance to phase of growth, availability of nutrients, other
      environmental conditions, and adaptations to stress into a single model wherein
      the bacterial cell uses the products of energy metabolism to detect its sense of
      well being and to alter its response to antibiotics (Fig. I). Levels of NADH and
      ATP are able to act as signaling molecules in both gram positive an gram negative
      bacteria to activate stress sigma factors and two component systems. In the
      future, a full understanding of the signaling pathways in bacterial pathogens may
      provide new targets for the development of drugs to reduce bacterial virulence
      and to enhance the activity of existing antibiotics.

PMID- 16904406
TI  - Schistosome resistance to praziquantel.
AB  - Praziquantel (PZQ) is the drug of choice for the treatment of human
      schistosomiasis. In 1994, it was first demonstrated that by sustained drug
      pressure on a Schistosoma mansoni strain in laboratory conditions resistance to
      PZQ can develop. Studies in Senegal and Egypt, both schistosomiasis endemic
      areas, have found that there are schistosome strain(s) that are tolerant to PZQ.
      In this article evidence from laboratory and field studies regarding the
      existence of PZQ resistance or tolerant schistosome strain(s) will be examined.

PMID- 16904407
TI  - Recent insights into platinum drug resistance in cancer.
AB  - Cisplatin and its analogs have become important components of chemotherapeutic
      regimens for the treatment of solid tumors, however, their overall effectiveness
      is limited by the emergence of drug-resistant tumor cells. Resistance to the
      platinum drugs is multifactorial consisting of mechanisms that prevent the
      formation of lethal platinum-DNA adducts and mechanisms that operate downstream
      of the drug/target interaction to promote cell survival. Continued progress in
      the study of the drug resistance phenotype as well as the development of new
      platinum analogs may eventually lead to improved therapies and increased survival
      rates.

PMID- 16904408
TI  - Multiple resistance mechanisms to azole antifungals in yeast clinical isolates.
AB  - The use of antifungal agents, especially the azole class, has increased in
      parallel with a higher incidence of fungal infections, particularly in
      immunocompromised patients. This situation has favored the appearance of Candida
      species, prominent among them C. albicans and C. globrata, with acquired
      resistance to these agents. This review focuses on the latest developments in
      investigations of molecular mechanisms contributing to azole resistance. Multiple
      resistance mechanisms have been described that can coexist in resistant clinical
      isolates. Understanding resistance mechanisms is of value not only for the design
      of new antifungal agents but also the development of strategies of overcome or
      delay the emergence of resistance.

PMID- 16904409
TI  - Drug resistance in Leishmania: similarities and differences to other organisms.
AB  - The main line of defense available against parasitic protozoa is chemotherapy.
      Drug resistance has emerged however, as a primary obstacle to the successful
      treatment and control of parasitic diseases. Leishmania spp., the causative
      agents of leishmaniasis, have served as a useful model for studying mechanisms of
      drug resistance in vitro. Antimonials and amphotericin B are the first line drugs
      to treat Leishmania followed by pentamidine and a number of other drugs.
      Parasites resistant against all these classes of drugs have been selected under
      laboratory conditions. A multiplicity of resistance mechanisms has been detected,
      the most prevalent being gene amplification and transport mutations. With the
      tools now available, it should be possible to elucidate the mechanisms that
      govern drug resistance in field isolates and develop more effective
      chemotherapeutic agents.

PMID- 16904411
TI  - Adding value to reproductive health research: communicating about the moral
      dimensions of science.

PMID- 16904412
TI  - Contraceptive usage, knowledge and correlates of usage among female emergency
      department patients.
AB  - OBJECTIVES: For female emergency department (ED) patients, we sought to assess
      the prevalence of contraceptive usage as well as the extent of contraceptive
      knowledge and to determine if demographic and sexual health history factors,
      comprehension of contraceptive methods and moral/religious opinions on
      contraception were associated with current usage of birth control pills (BCPs),
      prior usage of emergency contraception (EC) and frequency of condom usage.
      METHODS: English-speaking female ED patients aged between 18 and 55 years at a
      northeastern United States urban ED were surveyed on their usage, comprehension
      and opinions regarding BCPs, EC and condoms. RESULTS: Of the 539 respondents
      (64.6% were aged </=35 years), most were White (63.1%), single (42.5%), Catholic
      (48.4%) and privately insured (55.3%). Among the 223 women at pregnancy risk [not
      currently pregnant, not using any form of nonsurgical birth control (except
      condoms) and with no prior tubal ligation or hysterectomy], about 25% were using
      BCPs, fewer than 10% had used EC and almost 40% never used condoms. Most women
      displayed good knowledge about BCPs and condoms but poor understanding about EC.
      In multivariate logistic regression analyses, current BCP usage among women at
      risk of pregnancy was associated with younger age [odds ratio (OR)=0.54; 95%
      confidence interval (CI)=0.37-0.79], private insurance (OR=2.52; 95% CI=1.30
      4.86) and recent intercourse (OR=1.61; 95% CI=1.19-2.18). Among women at risk of
      pregnancy, those who had an abortion (OR=2.56; 95% CI=1.17-5.61) and those who
      displayed greater EC knowledge (OR=3.23; 95% CI=1.50-6.95) had greater odds of
      having used EC. Among all women, more frequent condom usage was associated with
      being younger (OR=0.57; 95% CI=0.46-0.70), having never been married (OR=0.44;
      95% CI=0.28-0.68) and not having intercourse recently (OR=0.79; 95% CI=0.64
      0.98). CONCLUSIONS: A high percentage of female ED patients (41.4%) were at risk
      of pregnancy. Demographic and sexual history factors can help identify women who
      might benefit from receiving referrals or education on contraceptive measures.

PMID- 16904413
TI  - Contraceptive failures and determinants of emergency contraception use.
AB  - OBJECTIVES: Two years after emergency contraceptive pills (ECPs) were made
      available without prescription in France, we investigated the determinants of ECP
      use in a representative sample of women at risk for unintended pregnancy. STUDY
      DESIGN: This study is based on data collected from a population-based cohort
      exploring contraceptive practices and abortion (N=2863). RESULTS: Among the 706
      women at risk for unintended pregnancy during the first year of follow-up (2001),
      only 11.1% used ECPs. Women in stable relationships or using the same
      contraceptive method during the year were less likely to use ECPs than other
      women. The study also demonstrates that detailed knowledge of ECPs increases the
      probability of its subsequent use. CONCLUSIONS: Given the low frequency of ECP
      use in cases of unintended pregnancy risk, these results suggest that information
      campaigns should be targeted not only at women with irregular contraceptive
      practices but also at women who experience errors in the use of their regular
      contraceptive method.

PMID- 16904414
TI  - Menstrual irregularity from hormonal contraception: a cause of reproductive
      health concerns in minority adolescent young women.
AB  - CONTEXT: Adolescents are frequent users of hormonal contraception (HC), yet their
      adherence to these methods is often poor. Concerns about side effects, especially
      those affecting the menstrual system, are often given as reasons for
      contraceptive nonadherence or discontinuation. We sought to identify teens'
      concerns and misperceptions about the menstrual-related side effects of HC.
      METHODS: Open focus groups were conducted with both sexually active and virgin
      adolescent women aged 12-18 years who were recruited from the Philadelphia area.
      The adolescents did not have to be contraceptive users in order to participate.
      The question put to each group was, "What are the things you have heard about the
      birth control pill, Depo-Provera and Norplant?" Groups were audio-recorded,
      transcribed and analyzed using qualitative software. RESULTS: We conducted 13
      female-only groups. Participants raised frequent concerns about menstrual-related
      side effects, believing that these side effects were evidence of possible
      negative effects of HC on their reproductive health. Four themes related to
      hormonal contraceptive-induced menstrual irregularity emerged from the groups.
      Theme 1: Menstruation is natural and should not be altered in any way. Theme 2:
      The menstrual period is necessary for cleansing of the body. Theme 3: "Spotting,"
      intermenstrual bleeding and amenorrhea cause doubts about the method's
      effectiveness and worries about pregnancy. Theme 4: All menstrual irregularity,
      from intermenstrual bleeding to amenorrhea, causes worry about the effects on
      fertility and on physical health. CONCLUSIONS: Teens have concerns about the
      menstrual irregularity caused by HC. Providers understand that these side effects
      are minor and of little medical consequence. Yet, adolescent patients may be
      ascribing great significance to these effects and may be declining these methods
      because of fear and misperceptions.

PMID- 16904415
TI  - Comparison profiles of cycle control, side effects and sexual satisfaction of
      three hormonal contraceptives.
AB  - OBJECTIVE: The objective of this study was to compare cycle control, tolerability
      and sexual well-being with the use of three hormonal contraceptives. METHODS: In
      this prospective randomized study, the effects of two combined oral
      contraceptives [20 microg of ethinylestradiol (EE)/100 microg of levonorgestrel
      and 15 microg of EE/60 microg of gestodene] were compared with those of the
      vaginal ring (15 microg of EE/120 microg of etonogestrel). One-year data from 280
      women were obtained. We investigated the pattern of menstrual cycle and the
      incidence of weight gain, nausea, headache, breast tenderness, irritability,
      depression and vaginal dryness. Moreover, desire and sexual satisfaction were
      evaluated. Finally, the cumulative rate of discontinuation in the three groups
      was estimated. CONCLUSION: The analysis of adverse events revealed two crucial
      points for acceptability, compliance and continuation: poor cycle control and
      disturbance of sexual intercourse due to vaginal dryness and loss of desire.

PMID- 16904416
TI  - Ethnic variations in sexual activity and contraceptive use: national cross
      sectional survey.
AB  - OBJECTIVES: Our objective was to compare data on contraceptive use in relation to
      reported sexual activity in women from different minority ethnic groups. DESIGN:
      We analyzed the National Survey of Sexual Attitudes and Lifestyles 2000.
      SUBJECTS: Women aged 16-44 years, numbering 6932 and residing in Britain,
      participated in this study. MAIN OUTCOME MEASURES: Our main outcome measures are
      as follows: percentage of women reporting sexual activity, use of contraception
      and type of contraception (hormonal, barrier or permanent methods). RESULTS:
      Overall, fewer women from the UK's four main ethnic minority groups reported
      recent sexual activity, compared with white women. Among sexually active women,
      contraceptive use was significantly lower in all ethnic minority groups than in
      white women, but this pattern differed according to marital status. In ever
      married or cohabiting women, lower contraceptive use was reported by Indian (78%)
      and Pakistani women (74%) than by other groups. Among single women, black
      Caribbean (88%) and black African (82%) women reported using less contraception
      compared with white (95%) and Indian (100%) women. Women from all ethnic minority
      groups were less likely than white women to report using hormonal contraception
      and permanent methods and were more likely to use barrier methods. The
      differences between ethnic groups remained significant after adjusting for
      educational achievement and parity. Deprivation and acculturation did not account
      for the use of contraception or the type of contraceptive method used.
      CONCLUSION: Sexually active married Pakistani and Indian women reported the
      lowest overall use of contraception. Among sexually active single women, black
      African and black Caribbean women reported levels of contraceptive use that were
      lower than those reported by white women. Sexually active women from all four
      minority ethnic groups were less likely than white women to use reliable methods
      of contraception.

PMID- 16904417
TI  - Changes in bleeding patterns with depot medroxyprogesterone acetate subcutaneous
      injection 104 mg.
AB  - OBJECTIVE: This study aims to assess changes in bleeding patterns with the use of
      depot medroxyprogesterone acetate (DMPA) 104 mg/0.65 ml subcutaneous injection
      (DMPA-SC 104). STUDY DESIGN: An analysis was conducted using data from two 1
      year, noncomparative clinical trials (N=1787) and a 2-year randomized study
      comparing DMPA-SC 104 (N=266) with DMPA intramuscular injection (DMPA-IM).
      Bleeding was analyzed per 30-day interval by category and number of days.
      Analyses also were performed for age and body mass index (BMI) subgroups and for
      the percentages of women shifting from bleeding/spotting to amenorrhea after each
      injection. RESULTS: Each study showed decreased incidence of irregular bleeding
      and increased amenorrhea with continued use of DMPA-SC 104. Rates of amenorrhea
      at Month 12 (52-64% across studies) and Month 24 (71% in the 2-year trial) were
      comparable with those originally reported for DMPA-IM. Changes in bleeding
      patterns showed no consistent differences according to age or BMI. The
      percentages of subjects shifting from bleeding and/or spotting to amenorrhea
      increased with each subsequent injection. CONCLUSION: Clinical data show that the
      incidence of amenorrhea increases over time with the use of DMPA-SC 104.

PMID- 16904418
TI  - Pharmacokinetics of chlormadinone acetate following single and multiple oral
      dosing of chlormadinone acetate (2 mg) and ethinylestradiol (0.03 mg) and
      elimination and clearance of a single dose of radiolabeled chlormadinone acetate.
AB  - BACKGROUND: Published data on pharmacokinetic parameters for chlormadinone
      acetate (CMA) are in part contradictory, especially with regard to terminal half
      life (t(1/2,z)). MATERIALS AND METHODS: Single and multiple doses of CMA (2 mg)
      and ethinylestradiol (EE; 0.03 mg) were administered to healthy female volunteers
      for six menstrual cycles. Plasma concentrations of CMA and EE were determined by
      gas chromatography-mass spectrometry. Single-dose and steady-state
      pharmacokinetic parameters were calculated. In a separate study, healthy female
      volunteers were given a single 2-mg dose of radiolabeled CMA. Concentrations of
      radioactivity in fecal and urine samples were determined via liquid
      scintillation. Excretion of total radioactivity was calculated as percentage of
      administered dose. RESULTS: Eighteen women completed the repeated-dose study.
      Peak plasma concentrations for CMA and EE were reached within 1 and 2 h after
      taking the study drug. Peak plasma concentrations of CMA were approximately 1600
      pg/mL after single-dose administration and 2000 pg/mL after multiple dosing. CMA
      and EE showed linear pharmacokinetics throughout six cycles, with constant trough
      values of approximately 400-500 pg/mL for CMA and 20-40 pg/mL for EE. Mass
      balance factors were 1.2-1.4 for CMA and 1.6-1.7 for EE, and accumulation factors
      were 1.7-2 for CMA and 1.7-1.8 for EE. Mean t(1/2,z) of CMA was approximately 25
      h after single dosing and 36-39 h at steady state. In the excretion balance
      study, mean dose of CMA recovered was 87.3+/-6.4%, with urinary and fecal
      excretion accounting for 45% and 42%, respectively. CONCLUSIONS: The
      pharmacokinetics of CMA and EE is linear after multiple dosing and remains stable
      during long-term administration, once steady state is reached. The t(1/2,z) of
      CMA was 36-39 h after multiple dosing, which is considerably shorter than the 80
      h often quoted in the literature.

PMID- 16904419
TI  - Does St. John's wort interfere with the antiandrogenic effect of oral
      contraceptive pills?
AB  - BACKGROUND: St. John's wort (SJW), a commonly used herbal remedy, has been shown
      to compromise the efficacy of drugs, including oral contraceptive pills (OCPs),
      by inducing cytochrome P-450. We investigated whether the simultaneous use of SJW
      with OCPs resulted in elevated serum androgen levels with implications of
      impaired OCP treatment of hirsutism and acne. MATERIALS AND METHODS: Fifteen
      healthy women were treated with the low-dose OC Loestrin 1/20trade mark for 2
      months and then additionally with SJW for 2 months. Androgen and sex hormone
      binding globulin (SHBG) levels were measured in serum by immunoassay methods;
      free testosterone (fT) was calculated. Results were analyzed using the Wilcoxon
      signed-rank test. RESULTS: There were no statistically significant differences in
      androgen levels after the addition of SJW in women using Loestrin 1/20trade mark.
      However, there were decreases in total testosterone and fT levels (10.7% and
      15.8%, respectively) along with a small increase in SHBG levels (7.0%).
      CONCLUSIONS: In women using OCPs and SJW simultaneously, it appears that SJW does
      not interfere with the antiandrogenic properties of OCPs.

PMID- 16904420
TI  - Cost-effectiveness of treatments for dysfunctional uterine bleeding in women who
      need contraception.
AB  - OBJECTIVE: This study aims to compare the cost-effectiveness of oral
      contraceptives (OCs), the levonorgestrel-releasing intrauterine system (LNG-IUS)
      and surgical management in treating dysfunctional uterine bleeding (DUB) in women
      not desiring additional children. METHOD: A Markov model was constructed from the
      perspective of the health services payers for a 5-year period. Treatment costs,
      DUB treatment success rates and contraception success rates were obtained through
      a literature review. RESULTS: In women not responding to an initial trial of OCs,
      surgical management was more effective than the LNG-IUS (95.5% vs. 92%) but at
      higher cost (US$4853 vs. US$2796 per woman). Among responders to OCs, continuing
      treatment with the LNG-IUS instead of OCs was more effective (92% vs. 90.4%) and
      less expensive (US$2796 vs. US$4711). For women naive to medical therapy, the LNG
      IUS and OCs had similar effectiveness, but cost for the LNG-IUS was lower
      (US$2796 vs. US$4895). In all scenarios, surgery followed if medical therapy
      failed; rates of primary method failure were 62.5% with OCs and 34% with the LNG
      IUS at 12 months. CONCLUSIONS: Treatment strategies employing the LNG-IUS are the
      most cost-effective in managing DUB, regardless of whether a woman has previously
      tried OC therapy.

PMID- 16904421
TI  - Bone mineral density in users of two kinds of once-a-month combined injectable
      contraceptives.
AB  - OBJECTIVE: The objective of this descriptive study was to compare bone mineral
      density (BMD) between users of two kinds of once-a-month combined injectable
      contraceptives (CICs) and control subjects. SUBJECTS AND METHODS: This cross
      sectional descriptive study included 97 women aged between 20 and 45 years using
      CICs containing either 25 mg of medroxyprogesterone acetate and 5 mg of estradiol
      cypionate for 12-82 months or 50 mg of norethindrone enanthate and 5 mg of
      estradiol valerate for 12-60 months, matched by age (+/-1 year) and body mass
      index (BMI; kg/m(2)) (+/-1) with users of the TCu 380A intrauterine device as
      control subjects. BMD was evaluated at the midshaft of the ulna and at the distal
      section of the radius of the nondominant forearm using double X-ray
      absorptiometry. RESULTS: There was no difference in BMD between users of either
      CIC and nonusers at either section of the forearm studied. There was also no
      difference in BMD between users of the two CICs at either section of the forearm.
      CONCLUSIONS: Women aged between 20 and 45 years, currently using one of these two
      kinds of CICs, presented BMDs similar to those of control subjects paired by age
      and BMI.

PMID- 16904422
TI  - Providing medication abortion information to diverse communities: use patterns of
      a multilingual web site.
AB  - OBJECTIVE: This study analyzes the use patterns of , an English-, Spanish-,
      Arabic- and French-language web site dedicated to three methods of early
      pregnancy termination: mifepristone/misoprostol, methotrexate/misoprostol and
      misoprostol alone. METHODS: This study examines both the overall and language
      specific use patterns of the web site from October 1, 2004, through September 30,
      2005. Data were recorded using Wusage 8.0, a web site statistics program.
      RESULTS: Over the 12-month study period, received more than 78,000 visits and
      nearly 240,000 page requests. The English version is the most popular version of
      the web site (accessed in 46.1% of all visits), followed by the Spanish (35.0%),
      Arabic (10.4%) and French (8.8%) versions. Spanish-language visits are nearly
      three times as likely to access the misoprostol-only section of the web site when
      compared with the other language versions (p<.001). CONCLUSION: This study
      confirms that multilingual, medically accurate online resources have the
      potential to expand information about medication abortion to both providers and
      women considering the option of abortion in diverse communities. Analysis of the
      language-specific use patterns highlights the different priorities of various
      types of web site visitors and suggests future priorities for educational
      outreach, collaboration and research.

PMID- 16904423
TI  - Introduction of the dilation and evacuation procedure for second-trimester
      abortion in Vietnam using manual vacuum aspiration and buccal misoprostol.
AB  - BACKGROUND: The dilation and evacuation (D&E) procedure was modified for use in a
      low-resource setting where access to electric vacuum aspiration is limited.
      METHOD: In this demonstration project, buccal misoprostol is used for cervical
      preparation, followed by evacuation using manual vacuum aspiration (MVA) and
      forceps. Senior physicians at the Hanoi Obstetrics and Gynecology Hospital were
      trained in D&E and subsequently conducted 439 D&E procedures. RESULTS: The
      primary outcomes were efficacy and safety. Secondary outcome measures include
      efficacy of buccal misoprostol for cervical preparation prior to D&E and the
      feasibility of MVA for use in the D&E procedure. CONCLUSION: Successful abortion
      took place in 100% of the cases. Three major complications occurred. This
      procedure may be appropriate in other low-resource settings lacking safe,
      effective abortion services in the second trimester.

PMID- 16904424
TI  - Obsessive-compulsive disorder: a 3-year prospective follow-up study of patients
      treated with serotonin reuptake inhibitors OCD follow-up study.
AB  - This study aimed to evaluate the long-term course of obsessive-compulsive
      disorder (OCD) in patients treated with serotonin reuptake inhibitors (SRIs) and
      to identify predictors of clinical outcome. Seventy-nine patients fulfilling DSM
      IV criteria for OCD were followed prospectively for 3 years. Baseline information
      was collected on demographic and clinical characteristics, using standardized
      instruments. During the follow-up period, the clinical status of each patient was
      evaluated monthly in the first year and bimonthly thereafter by means of the Yale
      Brown Obsessive Compulsive Scale (Y-BOCS) and the Hamilton Rating Scale for
      Depression (HDRS). The cumulative probability of achieving at least partial
      remission from obsessive-compulsive (OC) symptoms during the 3-year period was
      65%. The probability of full remission was 38%. For subjects who achieved at
      least partial remission, the probability of subsequent relapse was 60%.
      Significant predictors of poor outcome included a longer duration of illness, a
      greater severity of OC symptoms at intake, and the presence of comorbid
      schizotypal personality disorder. The findings confirm that the course of illness
      in OCD is usually continuous with fluctuations in the intensity of OC symptoms.
      Despite adequate SRI therapy, relatively few patients achieve a completely
      asymptomatic state, and of those who achieve at least a partial remission, a
      substantial proportion subsequently relapse. One third of OCD patients is
      treatment-resistant. Further studies with large samples are required to
      adequately identify predictors of long-term outcome of OCD in order to optimize
      the choice among the existing treatment modalities. The development of
      alternative strategies is needed to improve the treatment approaches for
      treatment-resistant OCD patients.

PMID- 16904425
TI  - Deflux for vesicoureteral reflux: pro--the case for endoscopic correction.

PMID- 16904426
TI  - Endoscopic treatment for vesicoureteral reflux: let's not get carried away!

PMID- 16904427
TI  - Role of vascular endothelial growth factor in prostate cancer.

PMID- 16904428
TI  - Impact of positive surgical margins after radical prostatectomy.

PMID- 16904429
TI  - Development of glomerulations in younger women with interstitial cystitis.
AB  - OBJECTIVES: To evaluate the consistency of cystoscopic findings with
      hydrodistension in younger women with a clinical diagnosis of interstitial
      cystitis. METHODS: A retrospective chart review was conducted of patients aged
      younger than 26 years old at the time of initial cystoscopy and hydrodistension
      at a single institution. Data included approximate duration of symptoms,
      development of visible terminal hematuria, presence of ulcers, and semiquantitive
      evaluation of degree of glomerulations (negligible, moderate, diffuse), and
      bladder capacity under anesthesia. RESULTS: Eighteen women aged 15 to 25 years
      old (mean, 17.5 years) were identified. The mean duration of symptoms was 38
      months, with an estimated mean age of onset of 16 years. No patient had Hunner's
      ulcers, and 13 had visible terminal hematuria with moderate-to-diffuse
      glomerulations. Ten women had repeat cystoscopies, and the mean time to repeat
      cystoscopy was 17 months. Three women underwent repeat cystoscopy and initially
      had a relatively normal bladder mucosa, with none or only rare glomerulations,
      but moderate-to-diffuse glomerulations were seen on the subsequent cystoscopy in
      addition to the development of terminal hematuria. One patient, conversely on
      subsequent cystoscopy, showed resolution of glomerulations. CONCLUSIONS:
      Interstitial cystitis symptoms can develop before an age where adult urologists
      or primary care physicians familiar with the diagnosis and treatment are usually
      involved with care. The cystoscopic appearance of the bladder wall after
      hydrodistension may not be constant over time, and the absence of initial
      findings of glomerulations or terminal hematuria does not preclude further
      development of these hallmarks of the disease on subsequent evaluation.

PMID- 16904430
TI  - Primitive neuroectodermal tumor: rare, highly aggressive differential diagnosis
      in urologic malignancies.
AB  - OBJECTIVES: Peripheral primitive neuroectodermal tumor (PNET) is a highly
      aggressive neoplasm belonging to the Ewing family of tumors. It is characterized
      by the expression of MIC2 and neural markers (eg, neuron-specific enolase,
      synaptophysin, S-100, vimentin, Leu-7), and the presence of the EWS-FLI1
      translocation. METHODS: We performed a MEDLINE search for PNET in urologic
      malignancies. Additionally, we report on 2 cases of renal and 1 case of bladder
      PNET. The data obtained by reviewing patients with renal PNET were analyzed using
      Kaplan-Meier analysis. RESULTS: Renal PNET is diagnosed in young adults (median
      age 24 years). In contrast, the incidence of bladder PNET seems to be dependent
      on a defective immune mechanism. Patients often present with pain (84%), palpable
      tumor (60%), and hematuria (38%). The radiologic findings are uncharacteristic;
      therefore, the diagnosis should be based on the histologic and
      immunohistochemistry findings. Renal and bladder PNET are both often diagnosed at
      an advanced stage and, therefore, the prognosis is poor, despite aggressive
      multimodal treatment (surgery, polychemotherapy, radiotherapy). We identified
      palpable tumor masses (log-rank test, P = 0.0027) and synaptophysin expression
      (log-rank test, P = 0.0422) as prognostic unfavorable markers for renal PNET.
      CONCLUSIONS: Renal PNET should be considered in young patients who present with
      the classic triad of renal cancer, hematuria, and pain and palpable tumor. Once
      PNET is diagnosed, multimodal treatment (radical surgery, multidrug chemotherapy,
      radiotherapy) must be initiated. Despite this, the prognosis is poor if distant
      metastases are present. Furthermore, palpable tumor masses and synaptophysin
      expression are associated with a shorter cancer-specific survival.

PMID- 16904431
TI  - Small intestine submucosa in urethral stricture repair in a consecutive series.
AB  - OBJECTIVES: To define the feasibility of acellular porcine small intestine
      submucosa (SIS) as a xenograft implant. SIS is commercially available and
      approved for use in humans. METHODS: Five patients underwent open surgery for
      urethral stricture repair using SIS and a four-layer SIS graft. Two patients had
      a bulbar stricture and three had a combined penile-bulbar stricture. The median
      stricture length was 9 cm (range 3.5 to 10). All patients underwent at least one
      internal urethrotomy. The urethral stricture repair was performed as an onlay
      urethroplasty. SIS was used to augment the urethral caliber at the stricture
      site. A catheter and percutaneous cystostomy for drainage were placed. The
      catheter was removed 10 days after surgery. Three weeks postoperatively, voiding
      cystourethrography and retrograde urethrography were performed. RESULTS:
      Preoperatively, flow studies were available for 3 patients, in 1 patient voiding
      was not possible because of urinary retention, and in 1 patient the preoperative
      flow study was not available (surgery was performed on the basis of the
      preoperative urethrographic findings). The mean maximal flow rate was 4.2 mL/s (n
      = 3); the mean value of the mean flow rate was 2.6 mL/s (n = 3). Postoperatively,
      1 patient had extravasation, which was treated by prolonged suprapubic drainage.
      One patient had severe urethritis and one urinary tract infection. Four patients
      had a recurrent stricture after a mean of 12.4 months (range 3.7 to 17.5). Two
      patients underwent open repair using buccal mucosa and two refused repeated
      surgery. CONCLUSIONS: In 4 patients, the operation was not successful. Because of
      the poor results, we discontinued the use of SIS for open urethral stricture
      repair.

PMID- 16904432
TI  - Preoperative computed tomography finding predicts for postoperative inguinal
      hernia: new perspective for radical prostatectomy-related inguinal hernia.
AB  - OBJECTIVES: To investigate the incidence of radical prostatectomy-related
      inguinal hernia (RPRIH) and the predictive factors for RPRIH. METHODS: We
      reviewed the medical charts of patients who had undergone retropubic radical
      prostatectomy (RRP) at our institution from January 2002 to December 2004 and had
      a median follow-up of 17 months (range 3 to 42). All patients were examined for
      RPRIH every 3 months. We also reviewed the computed tomography results in a
      blinded manner and investigated the predictive factors for RPRIH with
      multivariate analysis using the Cox proportional hazards model. RESULTS: Of 98
      patients analyzed, 17 were diagnosed with RPRIH after RRP (17.3%) at the median
      of 7 months (range 3 to 12). Preoperative computed tomography results were
      available for all patients, and subclinical inguinal hernia was identified in 20
      (20.4%) of the 98 patients. Multivariate analysis showed that a subclinical
      inguinal hernia was the single predictive factor for RPRIH. The estimated rate of
      RPRIH was 60.6% in the subclinical inguinal hernia group and 9.5% in the normal
      group at 12 months (log-rank test, P <0.001). CONCLUSIONS: The results of the
      present study have indicated that a preoperative computed tomography finding of a
      subclinical inguinal hernia predicts for postoperative inguinal hernia formation
      after RRP. RRP might only advance the time at which the inguinal hernia would
      develop with or without surgery. Thus, all patients with a subclinical inguinal
      hernia finding should be informed about the possibility of the development of
      RPRIH within 12 months after RRP and recommended to undergo surgical repair at
      RRP.

PMID- 16904433
TI  - Long-term durability of laparoscopic decortication of symptomatic renal cysts.
AB  - OBJECTIVES: To assess the long-term results of patient symptoms and radiologic
      outcomes of laparoscopic renal cyst decortication in the treatment of symptomatic
      simple renal cysts. Renal cysts are common in the adult population. Symptomatic
      renal cysts have traditionally been treated by percutaneous aspiration with or
      without injection of sclerosant agents; however, this has a high rate of
      recurrence. METHODS: From April 1994 through July 2005, 45 patients underwent
      laparoscopic decortication of symptomatic simple renal cysts with renal cyst wall
      excision and fulguration of the epithelial lining. Complex renal cysts were
      excluded. Of the 45 patients, 24 (53.3%) had undergone previous cyst aspiration
      with injection of sclerosant material for intended ablation. The Wong-Baker pain
      scale was used to assess the preoperative and postoperative pain scores.
      Radiologic success was indicated as no recurrence on the most recent computed
      tomography scan. RESULTS: Of the 45 procedures, 44 were completed
      laparoscopically. One patient (1.8%) underwent open conversion because of
      excessive bleeding. The mean operative time was 89 minutes (range 48 to 170).
      Symptomatic success was achieved in 91.1% of patients, with a median follow-up of
      52 months (range 3 to 132), and radiographic success was achieved in 95.5% of
      patients, with a median follow-up of 39 months (range 3 to 96). CONCLUSIONS: Long
      term follow-up has confirmed that laparoscopic cyst decortication is an effective
      and durable treatment option for symptomatic simple renal cysts during long-term
      follow-up. The greater and durable success rates of this minimally invasive
      technique may favor this treatment option over other treatment modalities.

PMID- 16904434
TI  - New-generation flexible ureterorenoscopes are more durable than previous ones.
AB  - OBJECTIVES: To determine the deterioration in the maximal active deflection and
      flow capabilities of a new-generation flexible ureteroscope (URS). METHODS: We
      performed 50 ureterorenoscopies using the same URS: a Karl Storz 11278 AU1 Flex
      X, which is capable of a 270 degree active deflection in the ventral and dorsal
      directions. Postoperatively, we evaluated the maximal active ventral and dorsal
      deflection, irrigation flow at 100 cm H2O, and the number of broken optical
      fibers. RESULTS: The URS was used for a total of 76 hours, 15 minutes (average 95
      minutes per procedure). The maximal ventral deflection had deteriorated from 270
      degrees to 208 degrees at the last procedure. The maximal dorsal deflection had
      decreased from 270 degrees to 133 degrees. The irrigation flow at 100 cm H2O had
      decreased from 50 mL/min initially to 40 mL/min at the last procedure. The number
      of broken image fibers had reached six at the 50th procedure. One repair was
      necessary at the 50th procedure because of a laser perforation of the working
      channel. CONCLUSIONS: The need for repair occurs less frequently with the new
      generation of URSs, especially when they are used by an experienced
      endourologist. In the future, improvements in the durability of the flexible URS
      will still be key for widespread use of the technique and especially to limit
      damage by the laser to the working channel.

PMID- 16904437
TI  - Development and validation of pheochromocytoma of the adrenal gland scaled score
      for predicting malignant pheochromocytomas.
AB  - OBJECTIVES: To evaluate the diagnostic performances of the pheochromocytoma of
      the adrenal gland scaled score (PASS) proposed in a previous report and that of a
      logistic model developed in this investigation. METHODS: In all 130 patients with
      malignant or assumed benign pheochromocytomas, 15 predictive variables were
      observed. Receiver operating characteristic (ROC) curve analysis was performed to
      evaluate the diagnostic performance of PASS. The logistic model was developed
      using the 15 predictive variables. Its performance was evaluated by calculating
      the area under the ROC curve and comparing it with that of the PASS. RESULTS: The
      PASS had the area under the ROC curve of 0.899 (95% confidence interval 0.844 to
      0.954). Of the 15 variables entered in the logistic regression analysis, 9 were
      retained in the model. The area under the ROC curve for the logistic model was
      0.983 (95% confidence interval 0.967 to 0.998). CONCLUSIONS: ROC analysis
      indicated that the PASS could be used for the diagnosis of malignant
      pheochromocytomas. The logistic model was able to improve the diagnostic
      performance of the PASS using a different variable weighting method. We
      emphasize, however, that a clinical prospective evaluation is needed to confirm
      their actual value.

PMID- 16904438
TI  - Reevaluation of TNM staging of renal cortical tumors: recurrence and survival for
      T1N0M0 and T3aN0M0 tumors are equivalent.
AB  - OBJECTIVES: The current TNM staging system for renal cortical tumors (RCTs)
      differentiates between tumors confined to the kidney (T1, T2) and tumors that
      extend through the renal capsule and invade into the perinephric fat (T3a). We
      examined the relative survival rates of patients with T1 and T3a tumors to
      determine the accuracy of the current TNM staging classification. METHODS: We
      analyzed the Columbia University Surgical Urological Oncology Database for all
      patients with clinically localized Stage T1, T2, and T3a RCTs treated surgically
      from 1988 to 2004. The primary outcomes included local and distant recurrence.
      Because the T3a classification is not limited by size, we compared T3a tumors
      with T1 tumors alone and tumors confined within the renal capsule (Stage T1 and
      T2 tumors combined). RESULTS: A total of 819 patients underwent partial or
      radical nephrectomy for RCTs at Columbia University during the study period.
      After the exclusion criteria were applied, 131 patients with T1N0M0, 19 patients
      with T2N0M0, and 82 patients with T3aN0M0 conventional renal cell carcinoma were
      eligible for analysis. The median follow-up was 37 months. The median tumor
      diameter was 3.2, 3.8, and 5.0 cm for Stage T1, T1 and T2 combined, and T3a
      lesions, respectively. The estimated 5-year disease-free survival was 95.2% and
      90.6% for T1 and T3a RCTs, respectively (P = 0.922). CONCLUSIONS: Patients with
      Stage T3a tumors experienced similar outcomes as patients with tumors confined to
      the renal capsule. These data suggest that the T3a classification should be
      examined more closely to attempt to improve the prognostic validity of the TNM
      classification.

PMID- 16904439
TI  - How does the radiographic size of a renal mass compare with the pathologic size?
AB  - OBJECTIVES: To investigate the relationship between the radiographic size on
      computed tomography and the pathologic size of renal tumors. METHODS: The records
      of 126 patients with a renal lesion suspicious for malignancy and with
      preoperative computed tomography performed 60 days or less before surgery at our
      institution were reviewed. The clinical size was defined as the largest diameter
      of the tumor seen on computed tomography and the pathologic size was defined as
      the largest diameter seen at pathology. The clinical and pathologic sizes were
      compared by size range and primary tumor stage. RESULTS: A total of 133 tumors
      from 126 patients were identified. Of the 133 tumors, 120 (90.2%) were renal
      carcinoma. The clinical and pathologic size for all 133 tumors was not
      significantly different (4.5 versus 4.1 cm, P = 0.35). The average clinical tumor
      size was larger than the pathologic tumor size for all sizes, except for 7 cm and
      greater. The difference reached statistical significance in all ranges from 1 to
      5 cm. The largest size difference was seen for tumors 4 to 5 cm, for which the
      average clinical size was 0.87 cm larger than the average pathologic size (P =
      0.025). CONCLUSIONS: Preoperative computed tomography imaging may slightly
      overestimate the pathologic size of renal tumors in certain size ranges. In
      pathologic Stage T1a tumors, the clinical tumor size was significantly larger
      than the pathologic stage (P = 0.009). The difference between the clinical and
      pathologic tumor size was greatest for tumors 4 to 5 cm. These results may affect
      decisions to perform nephron-sparing surgery in certain patients.

PMID- 16904440
TI  - Racial disparity in outcomes of a clinical trial population with metastatic renal
      cell carcinoma.
AB  - OBJECTIVES: Population studies have revealed that black Americans with renal cell
      carcinoma (RCC) have a shorter survival than do white Americans. Differences in
      socioeconomic status and treatment are frequently cited as the reasons for this
      disparity. The effect of these social obstacles may be reduced by studying a
      patient population with advanced RCC enrolled in clinical trials, because
      patients in these trials are likely to be similar in terms of their access to
      care, compliance, and performance status. METHODS: A retrospective review of all
      patients with metastatic RCC enrolled in clinical trials at Wayne State
      University from 1992 to 2002 was conducted. Log-rank survival analysis by age,
      sex, race, smoking history, nephrectomy history, prior therapy, type of protocol
      therapy (immunotherapy versus other), performance status (0 versus 1 to 2), and
      number of metastatic sites was conducted. Univariate and multivariate comparisons
      by race were performed for overall survival and time to progression. RESULTS: A
      total of 122 patients (median age 57 years) were enrolled; 21 (17%) were black
      and 101 (83%) were white. Overall survival was significantly shorter for the
      black Americans (P = 0.0027). The median survival for black Americans and white
      Americans was 6.9 and 11.5 months, respectively. On multivariate analysis, black
      race and performance status of 0 versus 1 and 2 were significant predictors of
      shorter survival. The presence of liver metastases and/or the absence of prior
      nephrectomy also influenced the length of overall survival through an interaction
      effect. CONCLUSIONS: Within a clinical trial patient population with RCC, race
      was a significant predictor of overall survival.

PMID- 16904441
TI  - Holmium laser enucleation versus open prostatectomy for benign prostatic
      hyperplasia: an inpatient cost analysis.
AB  - OBJECTIVES: To compare the cost of open transvesical prostatectomy (OP) with that
      of holmium laser enucleation (HoLEP) in the treatment of bladder outlet
      obstruction (BOO) attributed to benign prostatic hyperplasia. METHODS: From
      February to May 2004, 63 consecutive patients with symptomatic benign prostatic
      hyperplasia in a large prostate (70 to 220 g) and documented BOO were randomized
      to surgical treatment with OP (29 in group 1) or HoLEP (34 in group 2). All costs
      associated with the procedures during the hospital stay were recorded
      prospectively, and a cost-effectiveness analysis of the critical perioperative
      (ie, intraoperative and postoperative to hospital discharge) data was performed.
      RESULTS: The cost analysis showed a mean perioperative cost of 2868.9 euros
      (3556.3 dollars) for group 1 and 2356.5 euros (2919.4 dollars) for group 2. A
      direct comparison analysis showed that the most significant cost factors were the
      operative time (average 16.1% and 25.1% to the cost of OP and HoLEP,
      respectively), operating room surgical setup/disposables, including laser fiber
      and resectoscope loop in group 2 (average 13.3% and 29.3% to the cost of OP and
      HoLEP, respectively), and length of postoperative hospital stay (average 53.3%
      and 32.0% to the cost of OP and HoLEP, respectively). Overall, the
      hospitalization cost of HoLEP was 9.6% less than that for OP. CONCLUSIONS: Our
      data have demonstrated that HoLEP is associated with a significant hospital net
      cost savings compared with OP in patients undergoing surgery for symptomatic
      benign prostatic hyperplasia in large glands.

PMID- 16904442
TI  - Transurethral ethanol injection for prostatic obstruction: an excellent treatment
      strategy for persistent urinary retention.
AB  - OBJECTIVES: To evaluate the efficacy of transurethral ethanol injection into the
      prostate (TUEIP) for patients with persistent urinary retention resulting from
      benign prostatic hyperplasia or advanced prostate cancer. METHODS: Twenty-one
      Japanese men (elderly or at high risk anesthesiologically) who had developed
      persistent urinary retention because of benign prostatic hyperplasia or advanced
      prostate cancer were treated with TUEIP from January 2001 to January 2005.
      Patient age and preoperative prostate volume was 64 to 92 years (median 84) and
      24.1 to 125 cm3 (mean 57.6), respectively. Under sacral or lumbar anesthesia, 6
      to 14 mL (mean 10.6) of dehydrated ethanol (mean ratio for prostate volume 22.7%)
      was injected into the prostate under endoscopic guidance, followed by placement
      of an indwelling catheter. RESULTS: Of the 16 patients with benign prostatic
      hyperplasia and 5 with advanced prostate cancer, 14 (87.5%) and 3 (60%),
      respectively, were able to void spontaneously after catheter removal. The
      catheter had been left in place for 7 to 37 days (mean 12.4) after surgery. No
      additional treatment was required during the 2 to 24 months (mean 16) of follow
      up. The postoperative residual urine volume of these 17 patients was 20 to 150 mL
      (mean 60) and their mean prostate volume had decreased from 52.7 to 37.9 cm3
      (28.1% reduction) at 6 months postoperatively (P <0.001). No major complication
      was experienced. CONCLUSIONS: In patients with persistent urinary retention due
      to prostatic obstruction without severe complications, TUEIP removes the need for
      catheterization and allows spontaneous voiding. TUEIP may be an alternative to
      transurethral resection of the prostate for high-risk or elderly patients who
      cannot tolerate surgery.

PMID- 16904443
TI  - Urodynamic predictors of outcomes with photoselective laser vaporization
      prostatectomy in patients with benign prostatic hyperplasia and preoperative
      retention.
AB  - OBJECTIVES: To determine whether preoperative urodynamic parameters can predict
      the outcome in men in urinary retention and aid in counseling these men. METHODS:
      Forty men in urinary retention due to benign prostatic hyperplasia underwent
      photoselective laser vaporization prostatectomy (PVP). Preoperative urodynamic
      studies were used to identify the men with detrusor overactivity (DO) and
      impaired detrusor contractility (IDC). The International Prostate Symptom Score
      (IPSS), maximal flow rate, and postvoid residual urine volume were collected at
      1, 3, 6, and 12 months after PVP. RESULTS: Of the 40 men, 8 (20%) had IDC and 30
      had DO (75%) preoperatively. The men without preoperative DO had a significantly
      lower IPSS than those with preoperative DO at 1 month of follow-up. Men without
      preoperative IDC had a significantly lower IPSS and postvoid residual urine
      volume at the same point compared with men with preoperative IDC. The flow rate
      in men with preoperative IDC 1 and 6 months postoperatively was significantly
      lower than in men without preoperative IDC. CONCLUSIONS: Preoperative urodynamic
      parameters predict for outcome in men in urinary retention undergoing PVP. Men in
      urinary retention benefit from PVP with an improvement in both subjective and
      objective voiding function, regardless of the presence of DO or IDC.
      Postoperatively, patients with DO have more voiding symptoms than those without
      DO, and are almost twice as likely to require anticholinergics. Men without IDC
      have better IPSS, flow rates, and postvoid residual urine volumes compared with
      men with IDC. Of the 8 men with IDC, 3 required reoperation within the first
      year.

PMID- 16904444
TI  - Symptom assessment tool for overactive bladder syndrome--overactive bladder
      symptom score.
AB  - OBJECTIVES: Overactive bladder (OAB) is a common symptom syndrome with urgency,
      urinary frequency, and urgency incontinence. To collectively express OAB
      symptoms, we developed the overactive bladder symptom score (OABSS). METHODS:
      Four symptoms--daytime frequency, nighttime frequency, urgency, and urgency
      incontinence--were scored. The weighing score was based on a secondary analysis
      of an epidemiologic database. Psychometric properties were examined in five
      patient groups: OAB (n = 83), asymptomatic controls (n = 34), stress incontinence
      (n = 29), benign prostatic hyperplasia (n = 28), and other diseases with urinary
      symptoms (n = 26). RESULTS: The maximal score was defined as 2, 3, 5, and 5 for
      daytime frequency, nighttime frequency, urgency, and urgency incontinence,
      respectively. The sum score (OABSS 0 to 15) was significantly greater in the
      patients with OAB (8.36) than in the other patient groups (1.82 to 5.14). The
      distribution of the OABSS showed a clear separation between those with OAB and
      asymptomatic controls. The OABSS correlated positively with the individual scores
      (Spearman's r = 0.10 to 0.78) and quality-of-life scores assessed by the King's
      Health Questionnaire (Spearman's r = 0.20 to 0.49). The weighted kappa
      coefficients were 0.804 to 1.0 for each symptom score and 0.861 for OABSS. The
      posttreatment reduction in the OABSS was consistent with the global impression of
      patients of the therapeutic efficacy. CONCLUSIONS: The OABSS, the sum score of
      four symptoms (daytime frequency, nighttime frequency, urgency, and urgency
      incontinence), has been developed and validated. OABSS may be a useful tool for
      research and clinical practice.

PMID- 16904445
TI  - Long-term effects of ileal conduit urinary diversion on upper urinary tract in
      bladder cancer.
AB  - OBJECTIVES: To evaluate the functional and morphologic changes of the upper
      urinary tract after radical cystectomy and ileal conduit urinary diversion for
      bladder cancer. METHODS: Radical cystectomy and ileal conduit urinary diversion
      were performed in a total of 249 patients with bladder cancer at our hospital
      from 1980 to 1999. Of the 249 patients, 67 were excluded because of the presence
      of preoperative lesions in the upper urinary tract or elevated serum creatinine
      (greater than 1.4 mg/dL). Of the remaining 182 patients, 82 were also excluded
      because of incomplete follow-up or death less than 5 years after surgery.
      RESULTS: Of the 249 patients, a total of 100 (40.2%) who had no preoperative
      lesions in upper urinary tract and normal renal function and survived 5 years or
      longer were included in this analysis. The median follow-up period was 91 months
      (range 60 to 193). The serum creatinine was greater than the normal range in 10
      patients (10.0%), and radiologic changes in the upper urinary tract were observed
      in 14 patients (14.0%). They had diabetes mellitus nephropathy (4.0%) or specific
      comorbidities that could contribute to the deterioration of the upper urinary
      tract, such as ureteroileal anastomotic stricture (4.0%), chronic pyelonephritis
      (4.0%), urinary stones (1.0%), and upper urinary tract tumor (1.0%). CONCLUSIONS:
      The results of our study have shown that the functional and morphologic changes
      in the upper urinary tract after radical cystectomy and ileal conduit urinary
      diversion occur in patients with specific comorbidities that could contribute to
      those changes. Different from previous reports, none of the upper urinary tract
      changes developed without an obvious cause.

PMID- 16904446
TI  - Tolterodine extended release improves overactive bladder symptoms in men with
      overactive bladder and nocturia.
AB  - OBJECTIVES: To evaluate the efficacy and safety of nighttime dosing with
      tolterodine extended release (TER) in men with overactive bladder (OAB) and
      nocturia. METHODS: This was a post hoc analysis of data from two 12-week, double
      blind, placebo-controlled trials of nighttime (<4 hours before bedtime) TER (4 mg
      daily) dosing. Men with a mean micturition frequency of eight or more times in 24
      hours, including a mean of 2.5 or more nocturia episodes/night, were included.
      For each micturition, patients used 7-day diaries to record urinary urgency on a
      5-point urgency rating scale (1, none; 2, mild; 3, moderate; 4, severe; 5,
      urgency urinary incontinence). Micturitions were analyzed post hoc by urgency
      rating categories: total (1 to 5), non-OAB (1 to 2), OAB (3 to 5), and severe OAB
      (4 to 5). Adverse events were recorded throughout the study. RESULTS: A total of
      745 men (mean age 64 years) were randomized to placebo (n = 374) or TER (n =
      371). Of the 745 men, 73% reported no incontinence episodes in a 7-day diary at
      baseline. At week 12, the weekly values for nighttime severe OAB micturitions and
      24-hour and daytime total, OAB, and severe OAB micturitions were significantly
      reduced in the TER group versus the placebo group. The TER-treated men also
      reported a significant reduction in the mean urgency rating versus placebo.
      Adverse events associated with TER were low and comparable to those in the
      placebo group, with the exception of dry mouth (11% versus 4%). Withdrawals
      because of adverse events were infrequent (3% TER, 4% placebo). Five men were
      withdrawn for symptoms suggestive of urinary retention (3 TER, 2 placebo).
      CONCLUSIONS: Nighttime TER dosing reduced urgency-related micturitions and was
      well tolerated in men with OAB and nocturia.

PMID- 16904447
TI  - Inverted papilloma of urinary bladder: is long-term cystoscopic surveillance
      needed? A single center's experience.
AB  - OBJECTIVES: To review all cases of urinary bladder inverted papilloma (IP) in our
      institution and determine the need for cystoscopic surveillance. IP is an
      uncommon benign tumor of the urinary tract. Its multiplicity, recurrence, and
      association with transitional cell carcinoma (TCC) suggest possible malignant
      potential, leading to conflicting clinical conclusions regarding the need for
      surveillance. METHODS: All consecutive patients from January 1991 to December
      2004 with IP were included in this study. A single pathologist performed the
      histologic review. The patients had undergone cystoscopy and ultrasound
      evaluation of the kidneys every 6 months. RESULTS: Of the 52 patients, 45 were
      men and 7 were women. The average age at presentation was 58.9 +/- 11.8 years
      (range 30 to 79). No patient had a synchronous or previous bladder tumor. The
      most common complaint was macroscopic hematuria. Ten cases were incidental
      findings during bladder ultrasonography or cystoscopy. All were solitary tumors,
      most commonly found at the bladder neck. The average follow-up period was 62 +/-
      23 months, with no recurrence. One case of subsequent noninvasive papillary TCC
      developed 15 months later. The initial histologic findings had revealed cytologic
      atypia, with suspicious urine cytology findings. On review, it was more
      compatible with TCC with an inverted pattern. CONCLUSIONS: Although our cases
      exhibited benign biologic behavior, the presence of cytologic atypia and
      suspicious urine cytology require exclusion of TCC with an inverted pattern.
      Thus, in histologically proven solitary bladder IP with no associated TCC,
      cystoscopic surveillance may not be necessary.

PMID- 16904448
TI  - Prostatic tissue testosterone and dihydrotestosterone in African-American and
      white men.
AB  - OBJECTIVES: To compare tissue androgen levels in the prostate gland of African
      American and white men, looking for a possible explanation of the increased
      incidence of cancer in the former. METHODS: The subjects were 25 African-American
      and 36 white men, undergoing prostate biopsy consecutively, in whom cancer was
      absent. Biopsy cores (18 gauge) from the peripheral zone were homogenized,
      subjected to ether extraction, and separation by chromatography. Tissue
      testosterone and dihydrotestosterone (DHT) levels were determined by
      radioimmunoassay. RESULTS: The groups were matched for mean age (67.6 +/- 9.6
      years), prostate volume (37.9 +/- 21.0 cm3), body mass index (28.2 +/- 4.2
      kg/m2), and serum prostate-specific antigen (2.8 to 3.4 ng/mL) and testosterone
      (330 +/- 114 ng/dL) levels (P = NS for all measures). No significant difference
      in tissue testosterone (median 0.8 ng/g) or DHT (median 4.6 ng/g) was found
      between groups (P = NS). Furthermore, the tissue DHT/testosterone ratio
      (approximately 5) was not significantly different between the two groups (P =
      NS). CONCLUSIONS: Prostatic tissue levels of testosterone and DHT were similar in
      African-American and white men; thus, the present data do not support a
      hypothesis of increased androgenic activity in African-American men. Because the
      ratio of DHT/testosterone in prostatic tissue was similar in the two groups, the
      possibility of increased 5-alpha-reductase activity in African-American men did
      not seem likely. Using needle biopsy specimens, both absolute values and the
      ratio of the androgens in prostatic tissue were similar to those found in
      previous studies using surgically excised glands. Thus, quick-frozen biopsy cores
      appear to be a valuable tissue source for evaluating the androgen status within
      the prostate.

PMID- 16904449
TI  - Prostate-specific antigen-based serial screening may decrease prostate cancer
      specific mortality.
AB  - OBJECTIVES: To compare the preoperative characteristics, postoperative prostate
      specific antigen (PSA) doubling time (DT), and prostate cancer-specific mortality
      (PCSM) estimates after PSA failure in men diagnosed during a screening study
      versus a community referral population. A PSA-DT of less than 3 months is a
      surrogate endpoint for PCSM. METHODS: From 1988 to 2002, 1492 of 9637 patients
      with clinically localized prostate cancer underwent radical prostatectomy and
      experienced PSA failure. They were either participating in a screening study (n =
      841) or attended 1 of 44 community-based practices (n = 611). The distributions
      of PSA, Gleason score, tumor stage, and PSA-DT were compared using chi-square
      metric. The estimates of PCSM after PSA failure were compared using Gray's P
      value. RESULTS: Compared with the community population, the annually screened men
      experiencing PSA failure had a lower PSA level at diagnosis (5.1 versus 9.5
      ng/mL, P <0.0001), were less likely to have Gleason score 7 to 10 cancer (25.1%
      versus 42.1%, P <0.0001), and were more likely to have low-risk disease (64.5%
      versus 23.8%, P <0.0001). Furthermore, the screened cohort had a reduction (P
      <0.0001) in the proportion with a PSA-DT of less than 3, 3 to 5.99, and 6 to
      11.99 months and a significant increase in the proportion with a PSA-DT of 12
      months or longer. After a median follow-up of 4.5 and 4.1 years after PSA failure
      in the screened and community cohorts, respectively, the PCSM estimates were
      lower (P = 0.0002) in the screened cohort (10-year estimate 3.6% [95% confidence
      interval 1.3 to 5.8] versus 11.3% [95% confidence interval 5.9 to 17.4]).
      CONCLUSIONS: Patients diagnosed by annual prostate cancer screening appeared more
      likely to experience an indolent PSA recurrence and less likely to die of
      prostate cancer after PSA recurrence compared with patients referred from the
      community.

PMID- 16904450
TI  - Efficacy compared between caudal block and periprostatic local anesthesia for
      transrectal ultrasound-guided prostate needle biopsy.
AB  - OBJECTIVES: To investigate the clinical efficacy of a caudal block compared with
      periprostatic local anesthesia for transrectal ultrasound-guided multicore
      prostate needle biopsy. METHODS: A total of 100 patients who had undergone
      initial prostate biopsy using a systematic five-region biopsy by a single
      operator were investigated. The patients were randomly divided into two groups,
      with each group receiving a different anesthetic modality before biopsy. Group 1
      received periprostatic local anesthesia and group 2 received a caudal block. Both
      groups received 10 mL 1% lidocaine before biopsy. A 10-point visual analog scale
      was used to assess patient pain and anxiety. The duration between anesthesia
      induction and the beginning of the biopsy was measured. RESULTS: Patients who
      received local anesthesia (group 1) reported significantly less pain immediately
      after biopsy, with an average score of 1.1 compared with 2.1 in group 2 (caudal
      block, P = 0.01). Both groups were comparable regarding age, prostate-specific
      antigen level, digital rectal examination findings, prostate size, number of
      biopsy cores, level of prebiopsy anxiety, body mass index, and histologic
      findings. Group 1 required a significantly shorter period of anesthesia (198.5
      seconds) than did group 2 (594.5 seconds, P <0.0001). No anesthetic-related side
      effects occurred in either group. CONCLUSIONS: The results of our study have
      shown that the caudal block provides less effective anesthesia than periprostatic
      local anesthesia with the same dose of lidocaine for prostate biopsy. We have
      concluded that local anesthesia is a safe, simple, and rapid method of pain
      relief during prostate biopsy.

PMID- 16904451
TI  - Prostate volume and prostate-specific antigen levels in men enrolled in a large
      screening trial.
AB  - OBJECTIVES: Prostate volume correlates both with prostate-specific antigen (PSA)
      values and with the presence of benign prostatic hyperplasia (BPH). Here we
      examine the relationship between prostate volume and PSA level in a large,
      geographically diverse sample of men undergoing prostate cancer screening.
      METHODS: We followed 35,323 men enrolled in the Prostate, Lung, Colorectal and
      Ovarian (PLCO) Cancer Screening Trial. Each man was screened with digital rectal
      examination (DRE) and PSA levels for up to 4 years. Prostate volume was estimated
      by DRE performed by trained examiners at the PLCO sites. Linear and logistic
      regression was used to assess the effect of prostate volume and age on PSA
      levels. Regression coefficients were adjusted for the effect of prostate volume
      measurement error. RESULTS: Prostate volume estimated by DRE showed considerable
      measurement error. Averaging volume over screening visits and accounting for
      examiner bias greatly reduced this error. Linear regression analysis showed a
      slope of 0.030/cm3 of log PSA on prostate volume when correcting for measurement
      error (95% confidence interval [CI], 0.029 to 0.031). Age was independently
      associated with (log) PSA, with a slope of 0.022 per year. Logistic regression
      analysis of the risk of having an elevated PSA value (exceeding 4 ng/mL) showed
      an odds ratio of 1.9 (95% CI, 1.8 to 2.0) associated with a 10 cm3 increase in
      prostate volume. The correlation of log PSA and prostate volume was 0.37.
      Prostate volume was not correlated with body mass index and showed weak
      correlation (r = 0.14) with age. CONCLUSIONS: Prostate volume and age are
      independently associated with increased PSA levels in a population of men
      undergoing screening.

PMID- 16904452
TI  - Neuro-fuzzy system for prostate cancer diagnosis.
AB  - OBJECTIVES: To develop a neuro-fuzzy system to predict the presence of prostate
      cancer. Neuro-fuzzy systems harness the power of two paradigms: fuzzy logic and
      artificial neural networks. We compared the predictive accuracy of our neuro
      fuzzy system with that obtained by total prostate-specific antigen (tPSA) and
      percent free PSA (%fPSA). METHODS: The data from 1030 men (both outpatients and
      hospitalized patients) were used. All men had a tPSA level of less than 20 ng/mL.
      Of the 1030 men, 195 (18.9%) had prostate cancer. A neuro-fuzzy system was
      developed using the coactive neuro-fuzzy inference system model. RESULTS: The
      mean area under the receiver operating characteristic curve for the neuro-fuzzy
      system output was 0.799 +/- 0.029 (95% confidence interval 0.760 to 0.835), for
      tPSA, it was 0.724 +/- 0.032 (95% confidence interval 0.681 to 0.765), and for
      %fPSA, 0.766 +/- 0.024 (95% confidence interval 0.725 to 0.804). Furthermore,
      pairwise comparison of the area under the curves evidenced differences among
      %fPSA, tPSA, and neuro-fuzzy system's output (tPSA versus neuro-fuzzy system's
      output, P = 0.008; %fPSA versus neuro-fuzzy system's output, P = 0.032). The
      comparison at 95% sensitivity showed that the neuro-fuzzy system had the best
      specificity (31.9%). CONCLUSIONS: This study presented a neuro-fuzzy system based
      on both serum data (tPSA and %fPSA) and clinical data (age) to enhance the
      performance of tPSA to discriminate prostate cancer. The predictive accuracy of
      the neuro-fuzzy system was superior to that of tPSA and %fPSA.

PMID- 16904453
TI  - Bone metastases are infrequent in patients with newly diagnosed prostate cancer:
      analysis of their clinical and pathologic features.
AB  - OBJECTIVES: To investigate the clinical and pathologic characteristics of
      patients with bone metastases identified at the time of newly diagnosed prostate
      carcinoma at biopsy. METHODS: From November 2002 to May 2004, 1587 consecutive
      patients had a pathologic diagnosis of prostate cancer and underwent conventional
      technetium-99m methylene diphosphonate scintigraphy of the entire body. The
      clinical and pathologic features of those patients with positive bone scan
      findings (group 1) were compared with those of a subcohort of 372 patients with
      negative bone scan findings performed at the same nuclear medicine department
      (group 2). RESULTS: A retrospective complete data collection was available for
      1242 of 1587 patients. Bone metastases were found in 31 patients (2.5%). As
      expected, patients with skeletal metastases had a significantly greater mean
      serum total prostate-specific antigen level, and a Gleason sum of 8 or 9 was
      significantly more frequent in the pathologic findings of these subjects. Group 1
      patients had a significantly greater prevalence of previous nonprostate primary
      neoplasms (chi-square 12.74, df = 1, P = 0.0004) and reported a greater
      prevalence of current use of H2 blockers for the treatment and prevention of
      gastroesophageal reflux disorders (chi-square 37.52, df = 1, P < 0.0001) than did
      group 2 patients. CONCLUSIONS: Our data have confirmed that bone metastases are
      more frequent in patients with high prostate-specific antigen levels and poorly
      differentiated tumors at biopsy regardless of the patient's age. A history of
      previous nonprostate primary neoplasms and the use of H2 blockers seemed to be
      more prevalent in those patients with bone metastases at diagnosis.

PMID- 16904454
TI  - Radical prostatectomy for high-grade prostate cancer.
AB  - OBJECTIVES: Patients with high-grade clinically localized disease often have
      disease beyond the prostate and, if so, are unlikely to benefit from radical
      prostatectomy in the long-term. The objective of this study was to assess whether
      use of other known prognostic factors could be helpful in defining which men with
      Gleason 8 to 10 prostate cancer are most likely to benefit from surgical
      management. METHODS: A retrospective analysis was performed on men with biopsy
      Gleason 8 to 10 prostate cancer who underwent radical prostatectomy at two major
      university centers. No patients received hormonal therapy as part of initial
      treatment or adjuvant radiation therapy. Surgery was performed using a retropubic
      approach, and lymph node dissection was performed in all patients. Risk groups
      were defined based on prostate-specific antigen (PSA) value and percent positive
      biopsy cores (%PBC). A Cox proportional hazards analysis was performed to assess
      for differences in pretreatment prognostic factors. Kaplan-Meier curves were
      generated for each group, and then comparisons between groups were performed
      using log-rank analysis to assess for differences in 5-year actuarial freedom
      from biochemical failure. RESULTS: Radical prostatectomy was performed on 196
      patients between 1987 and 2002, of whom 168 had sufficient data for analysis.
      Median follow-up was 18 months (range, 1 to 130 months), with 31 patients at risk
      for more than 5 years. Patients with a PSA value of less than 10 ng/mL and %PBC
      of less than 50% had a 5-year actuarial biochemical control rate of 67% versus
      23% for all other patients (P = 0.0001). CONCLUSIONS: PSA value and %PBC are
      useful in selecting patients with high-grade prostate cancer most likely to
      benefit by radical prostatectomy.

PMID- 16904455
TI  - Usefulness of alpha1-antichymotrypsin-PSA complex for predicting bone metastases
      of prostate cancer.
AB  - OBJECTIVES: To determine the usefulness of alpha1-antichymotrypsin-prostate
      specific antigen (PSA) complex (PSA-ACT)-based parameters in predicting bone
      metastasis in patients with prostate cancer. METHODS: PSA-ACT, total PSA, free
      PSA, their volume-adjusted values, and alkaline phosphatase were evaluated in 220
      consecutive patients with newly diagnosed prostate cancer. RESULTS: Bone
      metastases were detected by bone scan in 27 (12.3%) of the 220 patients. The
      serum levels of PSA-ACT, total PSA, free PSA, PSA density, PSA adjusted for
      transition zone volume, PSA-ACT density, PSA-ACT adjusted for transition zone
      volume, alkaline phosphatase, PSA-ACT/PSA ratio, and Gleason score in patients
      with bone metastases were each significantly greater than in those without bone
      metastases. On receiver operating characteristic analyses, PSA-ACT had the
      greatest area under the curve (0.88), but the receiver operating characteristic
      curve demonstrated that the sensitivity and specificity of PSA-ACT were
      marginally better than those of total PSA at only a few selected cutoff points.
      At a sensitivity of 93% (2 patients with bone metastasis missed), unnecessary
      bone scans would have been avoided in 107 and 102 patients using a PSA-ACT cutoff
      value of 10 ng/mL and total PSA cutoff value of 11.5 ng/mL, respectively.
      Multivariate logistic regression analysis demonstrated that PSA-ACT and Gleason
      score were significant independent predictors of bone metastasis. CONCLUSIONS:
      PSA-ACT is as useful as total PSA for identifying patients with a low probability
      of having bone metastasis. PSA-ACT could replace PSA for predicting negative bone
      scans in a clinical setting in which PSA-ACT is used for monitoring and screening
      patients for prostate cancer.

PMID- 16904456
TI  - Transperitoneal versus extraperitoneal laparoscopic radical prostatectomy:
      experience of a single center.
AB  - OBJECTIVES: To analyze, in a consecutive study, the perioperative, postoperative,
      and functional results of the transperitoneal and extraperitoneal approaches for
      laparoscopic radical prostatectomy. METHODS: A total of 160 patients underwent
      radical prostatectomy and were subdivided into two groups. Group 1 underwent the
      transperitoneal approach and group 2, the extraperitoneal approach. The
      preoperative parameters, age, prostate-specific antigen level, biopsy Gleason
      score, American Society of Anesthesiologists class, body mass index, and clinical
      stage, were considered. The perioperative parameters evaluated were the operative
      time, blood loss, blood transfusion, hospital stay, catheterization time,
      complications, histopathologic findings, TNM stage, Gleason score, prostate and
      tumor volumes, and functional results. RESULTS: The patients in both groups had
      comparable preoperative data. No differences were observed between the two groups
      in the intraoperative data, except for the mean operative time (179 +/- 54.6 for
      group 1 versus 133.7 +/- 27 minutes for group 2). Also, no differences were
      observed between the two groups in terms of the postoperative data. The
      proportion of complications was 21.25% in group 1 and 22.5% in group 2. We
      recorded symptomatic lymphocele requiring treatment with a drain or reoperation
      in 8 patients (10%) in group 2 and 0% in group 1 (P <0.001) of all the patients
      who underwent lymphadenectomy. The rate of positive surgical margins was 25% for
      group 1 and 21.25% for group 2 (P = NS). For those with Stage pT2, the positive
      margin rate was 7.3% and 10% for groups 1 and 2, respectively. The recovery of
      continence at 3 months was faster in group 2 (75% of patients versus 50.9% in
      group 1; P <0.01). CONCLUSIONS: The extraperitoneal approach required less
      operative time and enabled faster recovery of continence and the transperitoneal
      approach prevented the formation of lymphocele.

PMID- 16904457
TI  - Microsurgical "testis-sparing" surgery for nonpalpable hypoechoic testicular
      lesions.
AB  - OBJECTIVES: With the increased use of trans-scrotal ultrasonography, the
      unexpected detection of nonpalpable hypoechoic testicular lesions has become more
      frequent. The different approaches vary from radical orchiectomy to simple
      ultrasound follow-up, but definitive guidelines do not yet exist about the
      management of these lesions. We report our series of patients with hypoechoic
      testicular lesions who underwent surgical exploration with the aid of an
      operating microscope. METHODS: A total of 7 patients were considered for
      microsurgical exploration of a nonpalpable hypoechoic testicular lesion from
      April 2003 to June 2005. The hospital records and ultrasound and operative
      reports were reviewed retrospectively. RESULTS: The side of the lesion was the
      left testis in 4 patients and the right testis in 3. The mean size of the
      hypoechoic area was 5.7 +/- 4.6 mm (range 2.5 to 16). The microsurgical technique
      allowed us to identify and successfully excise the lesion in all patients.
      Intraoperative frozen section examination revealed a benign lesion in 6 cases and
      testicular intraepithelial neoplasia in 1. The patient with testicular
      intraepithelial neoplasia underwent radical orchiectomy. The definitive
      histologic analysis always confirmed the frozen section examination report. The
      patients were evaluated clinically and by ultrasonography for a mean follow-up of
      15 months. No complications occurred. CONCLUSIONS: Microsurgical exploration of
      the testis combined with frozen section examination represents a safe, effective,
      and reliable technique for evaluation of nonpalpable hypoechoic testicular
      lesions. This approach has significant advantages and should be considered in
      particular for patients with a solitary testis or presenting with bilateral
      lesions and wishing to father a child.

PMID- 16904458
TI  - An integrated analysis of alprostadil topical cream for the treatment of erectile
      dysfunction in 1732 patients.
AB  - OBJECTIVE: To assess the safety and efficacy of topical alprostadil cream for
      erectile dysfunction (ED). METHODS: Patients with an ED score of 25 or less on
      the erectile function domain of the International Index of Erectile Function
      (IIEF) were randomly assigned to placebo or topical alprostadil cream (100, 200,
      or 300 microg) for at-home use for 12 weeks in two multicenter, double-blind,
      parallel-group studies. Patients receiving organic nitrates and patients with
      diabetes were included. Primary end points included the change in score for the
      erectile function domain of the IIEF and the change from baseline for the Sexual
      Encounter Profile (SEP) questions 2 (vaginal penetration success) and 3
      (maintenance of erection to ejaculation). Safety was based on observed and
      reported adverse events and clinical laboratory results. Data from each study
      were pooled into a single integrated analysis. RESULTS: A total of 1732 patients
      received placebo (n = 434) or topical alprostadil cream at 100 microg (n = 434),
      200 microg (n = 430), or 300 microg (n = 434). The mean changes from baseline to
      end point in IIEF erectile function (EF) domain scores were -0.7, 1.6, 2.5, and
      2.4 points for each group, respectively (P <0.001). Scores on SEP questions 2 and
      3 improved slightly but significantly for all drug treatment groups compared with
      placebo (P <0.001). Most adverse events were localized to the application site
      and resolved within 2 hours. CONCLUSIONS: Topical alprostadil cream significantly
      improves ED in a broad range of patients. Most adverse events were limited to the
      application site and were generally well tolerated.

PMID- 16904459
TI  - Insight on pathogenesis of varicoceles: relationship of varicocele and body mass
      index.
AB  - OBJECTIVES: Varicoceles, present in 15% to 20% of men, are the most common
      abnormal finding among men presenting with infertility, yet controversy exists
      regarding their etiology. Anecdotal experience suggests that varicoceles are more
      prevalent in lean men, supporting the "nutcracker" effect of the superior
      mesenteric artery compressing the left renal vein over the aorta. We examined
      this hypothesis in a large adult population. METHODS: A total of 2106 men were
      evaluated for infertility or erectile dysfunction from 1990 to 1996. The men were
      examined for the presence and severity of a varicocele. The association between
      age, height, body mass index, year of evaluation, and reason for consultation and
      the presence and severity of a varicocele was examined using logistic regression
      analysis. RESULTS: The mean age was 47 years (range 18 to 85), and the median
      body mass index was 26.4 kg/m2 (range 15.4 to 53.3). A varicocele was present in
      398 men (18.9%). Stratified by grade, 59 (14.8%) were grade III, 155 (38.9%) were
      grade II, and 184 (46.2%) were grade I. The prevalence of varicoceles in the
      erectile dysfunction group (12.7%) was significantly less (P <0.001) than in the
      infertile group (32.2%). Multivariate logistic regression analysis revealed a
      statistically significant inverse relationship between body mass index and the
      presence of a varicocele. CONCLUSIONS: Varicoceles were less likely to be
      diagnosed among obese men. Although this suggests that the "nutcracker"
      phenomenon or other biophysical effects of increased adiposity may play a role in
      the pathogenesis, other factors could not be excluded as contributing to our
      findings.

PMID- 16904460
TI  - Vardenafil rescue rates of sildenafil nonresponders: objective assessment of 327
      patients with erectile dysfunction.
AB  - OBJECTIVES: To prospectively investigate whether vardenafil can effectively treat
      patients for whom sildenafil (100 mg) has failed. The introduction of two new
      oral phosphodiesterase type 5 inhibitors (tadalafil and vardenafil) raises the
      question of whether the new agents will permit us to treat sildenafil
      nonresponders with another oral agent. METHODS: Patients were seen at one
      institution during a 5-year period. A total of 327 patients complaining of
      sildenafil-refractory erectile dysfunction underwent intracavernous pharmacologic
      injection and color duplex Doppler ultrasonography. Subsequently 59 of these men
      tried vardenafil home dosing. RESULTS: Of the 327 men in whom sildenafil failed,
      16% were younger than 50, 21% were 51 to 60, 34% were 61 to 70, and 28% were
      older than 70 years. The Doppler diagnoses were arterial insufficiency in 154
      (47%), mixed vascular insufficiency in 73 (22%), and cavernous venous occlusive
      disease in 57 (17%). Forty-three men (13%) had normal erectile responses to
      prostaglandin E1 (10 to 20 microg). Of the 59 men who tried vardenafil, 19% were
      younger than 50, 17% were 51 to 60, 40% were 61 to 70, and 23% were older than 70
      years. The Doppler diagnoses were arterial insufficiency in 28 (42%), mixed
      vascular insufficiency in 10 (19%), and cavernous venous occlusive disease in 15
      (29%). Six men (8%) had normal erectile responses to prostaglandin E1. Only 7
      (12%) of the 59 men reported that home vardenafil dosing resulted in successful
      intercourse. CONCLUSIONS: An appropriate diagnostic evaluation and subsequent
      treatment algorithm have yet to be established for those for whom
      phosphodiesterase type 5 inhibitors fail. We found that most sildenafil
      nonresponders had severe arterial insufficiency and were older, with 62% older
      than 60 years. Our preliminary experience suggests that only a small percentage
      (12%) of sildenafil nonresponders can be salvaged with vardenafil.

PMID- 16904461
TI  - Incidence of testicular germ cell cancers in U.S. children: SEER program
      experience 1973 to 2000.
AB  - OBJECTIVES: The incidence of testicular cancer in white adults in the United
      States increased during most of the last half of the 20th century, but
      information on trends in the occurrence of prepubertal testicular cancer is
      lacking. We analyzed a population-based cohort to determine whether the incidence
      trends of prepubertal testicular germ cell tumors have risen similarly to those
      seen in adult testicular tumors. METHODS: We identified cases of histologically
      confirmed germ cell testicular cancer in boys aged 0 to 14 years, of all races,
      from 1973 to 2000, through the Surveillance, Epidemiology, and End Results
      program of the National Cancer Institute. The variables analyzed included age,
      race, tumor histologic type, and year of diagnosis. RESULTS: A total of 131 cases
      of testicular germ cell cancer were diagnosed among boys of all races, with an
      overall incidence of 1.6 cases per 1 million person-years. Yolk sac tumor was the
      most common, followed by teratoma. Choriocarcinoma and seminoma were equally
      rare. Tumors were most common among whites during early infancy. No secular
      trends in incidence rates were identified. CONCLUSIONS: Prepubertal testicular
      cancer is rare. All tumors were more common in whites. In contrast to adult
      testicular cancer, no clear trend over time was found for prepubertal tumors.
      Whatever the reasons for the increased incidence of testicular cancer over time
      in men, they do not seem to bear on the risk of testicular cancer in boys.

PMID- 16904463
TI  - Association between primary nocturnal enuresis and habitual snoring in children.
AB  - OBJECTIVES: Nocturnal enuresis has been associated with obstructive sleep
      disordered breathing mostly in hospital-referred adults and children. To
      investigate whether primary nocturnal enuresis is significantly associated with
      habitual snoring in the general pediatric population irrespective of subjects'
      age and sex, we studied children attending six randomly selected schools in a
      city in central Greece. METHODS: A questionnaire regarding the symptoms of sleep
      disordered breathing and the presence of nocturnal enuresis (bedwetting for at
      least one night per week) was answered by the children's parents. RESULTS: A
      total of 1821 children (age 5 to 14 years; 896 girls) were included in the study.
      Of these, 135 (7.4%) were snoring more frequently than three nights per week
      (habitual snorers). The habitual snorers had a history of primary nocturnal
      enuresis more often than did nonhabitual snorers (7.4% versus 2%; odds ratio
      4.00, 95% confidence interval 1.93 to 8.32). The association of primary nocturnal
      enuresis with habitual snoring remained significant after adjustment for age and
      sex (odds ratio 3.54, 95% confidence interval 1.68 to 7.44). CONCLUSIONS: In a
      community sample of children, those with habitual snoring more often had primary
      nocturnal enuresis than did those without snoring.

PMID- 16904464
TI  - Results of microsurgical subinguinal varicocelectomy in children and adolescents.
AB  - OBJECTIVES: To report our experience with microsurgical subinguinal
      varicocelectomy in boys younger than 18 years old. METHODS: A total of 92 boys
      with a mean age of 15.8 years (range 11 to 18) underwent microsurgical
      subinguinal varicocelectomy because of ipsilateral testicular hypotrophy (n =
      63), pain, or parental preference. The varicoceles were grade III in 82 (89.1%)
      and grade II in 10 (10.9%) boys. Microsurgery was assisted by an operating
      microscope (10x to 25x) and Doppler probe. All boys were discharged home on the
      same day of surgery. RESULTS: Of the 92 patients, 78 attended the initial
      postoperative visit at 1 month and 61 attended the 1-year follow-up visit. At 1
      year, 40 (65.6%) of 61 testes demonstrated catch-up growth, with no evidence of
      testicular loss or persistent hypotrophy in the other 21. The only complication
      was persistent scrotal pain in 1 patient. At 1 year of follow-up, 1 patient
      (1.6%) had a recurrence and no patients had hydrocele formation or evidence of
      testicular loss or persistent hypotrophy. CONCLUSIONS: Microsurgical subinguinal
      varicocelectomy is a safe, effective, and minimally invasive treatment modality
      in children and adolescents.

PMID- 16904465
TI  - Laparoscopic calicovesicostomy: a novel surgical procedure.
AB  - Laparoscopic calicovesicostomy in the horseshoe kidney with ureteropelvic
      junction obstruction associated with ipsilateral ureteral duplication and a large
      capacity bladder is described. The intraoperative and postoperative clinical
      parameters were satisfactory in this preliminary report. Additional studies are
      necessary to evaluate this novel surgical procedure.

PMID- 16904466
TI  - Use of BioGlue in laparoscopic partial nephrectomy.
AB  - Hemostasis during laparoscopic partial nephrectomy continues to be a challenging
      problem for the laparoscopic surgeon. We have found BioGlue to be highly
      effective as a hemostatic agent during laparoscopic partial nephrectomy.

PMID- 16904467
TI  - Reconstruction of wide scrotal defect using superthin groin flap.
AB  - INTRODUCTION: Grafts and flaps have been widely used to reconstruct scrotal
      defects due to Fournier's gangrene. Controversy still exists concerning the use
      of grafts and flaps because of the low protection provided by the grafts and the
      high volume of the flaps. We describe the use of an expanded groin flap for
      scrotum reconstruction. TECHNICAL CONSIDERATIONS: Three patients were treated for
      total scrotal tissue loss using this method. An expander was installed through an
      incision from the inferolateral aspect of the groin, and superthin flaps obtained
      after 3 weeks were dissected starting from the medial side. Care was taken during
      dissection, because the skin was thin on the lateral side, and dissection was
      performed in a subfascial fashion. Finally, the defect was covered with the
      lateral part of the expanded flap and the donor site was primarily closed.
      CONCLUSIONS: To cover the testes, both the aesthetic and functional state should
      be taken into consideration. Therefore, a thin and durable cover is required for
      scrotal reconstruction. The expanded superthin groin flap possesses these
      features and is a good option.

PMID- 16904468
TI  - Transfascial vaginal tape for surgical treatment of stress urinary incontinence.
AB  - INTRODUCTION: In the past decade, two minimally invasive, mid-urethral sling
      procedures have been developed to correct stress urinary incontinence: the
      tension-free vaginal tape and the transobturator tape. Using similar surgical
      principles, we describe the placement of a sling located at the mid-urethral
      level and placed laterally in the previously perforated endopelvic fascia. This
      technique was termed transfascial vaginal tape. TECHNICAL CONSIDERATIONS: A 2 to
      3-cm-long vertical incision was made at the mid-urethral level. A suburethral
      tunnel was created bilaterally in the anterior vaginal wall until the endopelvic
      fascia and retropubic space were reached. A 1.5 x 8-cm monofilament polypropylene
      mesh was placed under the mid-urethra and laterally in the previously perforated
      endopelvic fascia. Bilaterally, the sling was sutured to the urethropelvic
      ligaments. CONCLUSIONS: We describe a new, simple, safe, minimally invasive,
      tension-free, and cost-effective technique for the treatment of female stress
      urinary incontinence.

PMID- 16904469
TI  - Management of a malignant urinary fistula by ureteral embolization with coils.
AB  - We report the case of a 42-year-old man with a synovial sarcoma of the prostate,
      metastatic at presentation, who after aggressive chemotherapy followed by
      extensive surgery developed a complex pelvic fistula involving the lower ureter,
      bladder, and enteral structures. The patient was a poor candidate for surgery
      because of his short life expectancy and poor health status. Conservative
      management with bilateral nephrostomy tubes did not allow sufficient fistulous
      output for symptomatic relief. Using the percutaneous access already in place, we
      performed bilateral ureteral embolization with coils. Complete ureteral occlusion
      was obtained with a minimally invasive procedure and allowed total symptomatic
      relief.

PMID- 16904470
TI  - Renal primitive neuroectodermal tumor in childhood with intracardiac extension.
AB  - Primary primitive neuroectodermal tumors of the kidney are exceptionally rare and
      usually affect children and young adults. We report the first pediatric case of
      renal primitive neuroectodermal tumor presenting with tumor extension along the
      inferior vena cava to the right ventricle. This case highlights that when
      considering a renal tumor with significant intravascular extension in the
      pediatric age group, although the most likely diagnosis remains Wilms tumor,
      other rare entities may also demonstrate similar clinical and imaging features.

PMID- 16904471
TI  - Benign fibrous pseudotumor of tunica vaginalis testis.
AB  - We discuss the rare benign paratesticular mass identified as fibrous pseudotumor.
      We performed a published data search to review the etiology, incidence, gross and
      microscopic examinations, and pathologic diagnostic considerations. Fibrous
      pseudotumor is a rare, benign lesion. Histologic examinations, as well as
      concerted efforts between the pathologist and surgeon, are necessary for
      appropriate diagnosis and treatment.

PMID- 16904472
TI  - Giant cell fibroblastoma of the penis.
AB  - Giant cell fibroblastoma (GCF) is an uncommon fibroblastic tumor of childhood.
      Appearing as superficial, poorly circumscribed masses, they are characterized
      histologically by a mixture of cellular and angiectoid areas with empty cleft
      like spaces, lined by spindle-shaped and multinucleated giant cells. We present a
      case of an 11-month-old boy with penile GCF treated with local excision. The
      patient presented with a recurrent penile mass 1 year later and underwent repeat
      excision. Pathologic examination confirmed recurrent GCF. GCF is a benign, but
      locally recurrent tumor, as demonstrated by our case. To our knowledge, no cases
      of penile involvement have been previously reported.

PMID- 16904473
TI  - Treatment of primary hyperoxaluria type 1 with sequential liver and kidney
      transplants from the same living donor.
AB  - Alanine-glyoxalate aminotransferase deficiency occurs in patients with primary
      hyperoxaluria type 1. Increased hepatic oxalate production leads to high urine
      concentrations of glycolate and oxalate. Calcium oxalate nephrolithiasis and
      nephrocalcinosis occur, and renal function progressively declines until patients
      develop end-stage renal disease. Renal transplantation alone is inadequate
      therapy because the primary enzyme deficiency remains. We report what we believe
      to be the second-youngest recipient to undergo successful sequential liver and
      kidney transplantation from a single living-related donor for treatment of
      primary hyperoxaluria type 1. We also discuss the changes in this patient's serum
      oxalate levels after transplantation.

PMID- 16904474
TI  - Mixed germ cell tumor in intra-abdominal testis associated with ipsilateral
      ectopic dysplastic kidney.
AB  - Testicular tumor of the cryptorchid testis associated with renal dysplasia is
      relatively infrequent and indicates maldevelopment during embryogenesis. We
      report a case of a 31-year-old man with a mixed germ cell tumor found in an intra
      abdominal testis associated with an ipsilateral ectopic dysplastic kidney. He
      underwent orchiectomy with partial cystectomy. Simple nephrectomy was also
      performed. No evidence of disease recurrence was found at 16 months of follow-up.

PMID- 16904475
TI  - Appendiceal carcinoma masquerading as recurrent urinary tract infections: case
      report and review of literature.
AB  - We report on a female patient who presented with recurrent urinary tract
      infections. The investigations revealed an adenocarcinoma of the appendix
      fistulating into the bladder and causing irritative symptoms. After right
      hemicolectomy and partial cystectomy, she was well at 3 months without any need
      for adjuvant therapy. This unusual situation reminds us that the finding of
      bladder adenocarcinoma is rare, and it would be prudent to examine the lower
      gastrointestinal tract thoroughly to look for a bowel source, before recommending
      any ablative surgery.

PMID- 16904476
TI  - Isolated recurrence of ductal prostate cancer to anterior urethra.
AB  - We report the case of a 74-year-old man with ductal prostate cancer who had
      originally undergone radiotherapy but developed metastases to the anterior
      urethral mucosa. This is the fourth such case ever reported in English
      publications. We suspect the metastases developed from implantation after
      instrumentation, a common finding in the previously reported cases. Although no
      specific treatment regimen exists, we believe that local resection followed by
      androgen deprivation is the treatment of choice in these patients.

PMID- 16904477
TI  - Solitary ureteral metastases of renal cell carcinoma.
AB  - Metachronous presentation of metastatic renal cell carcinoma (RCC) to the ureter
      is extremely rare. We report a solitary metachronous metastatic RCC in the
      contralateral ureter 14 months after right radical nephrectomy for Fuhrman grade
      2 pT3a clear cell disease after the patient re-presented with gross hematuria.
      The proximal left ureteral lesion was excised followed by ileal-ureteral
      interposition. Pathologic examination confirmed metastatic RCC. To date, only 51
      cases of metastatic RCC to the ureter have been reported, with only 6 occurring
      metachronously in the contralateral ureter. Also, we report the presence of focal
      extramedullary hematopoiesis occurring within this metastatic lesion.

PMID- 16904478
TI  - Nonoperative management of abdominoscrotal hydroceles in an infant.
AB  - Early surgery is recommended for infant abdominoscrotal hydrocele because
      spontaneous resolution has not been reported. We present a 6-month-old boy with
      bilateral abdominoscrotal hydrocele, who did not undergo surgery because of a
      hematologic condition. After 1 year, the abdominal portion of both hydroceles
      resolved, leaving simple bilateral scrotal hydroceles.

PMID- 16904479
TI  - Vardenafil prevents fibrosis and loss of corporal smooth muscle that occurs after
      bilateral cavernosal nerve resection in the rat.
AB  - OBJECTIVES: Impotence, specifically corporal veno-occlusive dysfunction (CVOD),
      occurs after radical prostatectomy. It results from the effects of cavernosal
      nerve damage, which causes smooth muscle (SM) loss and an increase in collagen
      within the corpora. Recent reports have suggested that long-term treatment with
      phosphodiesterase-5 inhibitors after radical prostatectomy may prevent such
      changes. We aimed to determine whether bilateral cavernosal nerve resection
      (BCNX) in the rat leads to CVOD and whether long-term phosphodiesterase-5
      inhibition ameliorates these histologic and functional impairments. METHODS: Rats
      (n = 7 to 11/group) underwent either the sham operation, BCNX, or BCNX plus 30
      mg/L vardenafil in the drinking water. Before the rats were killed 45 days later,
      CVOD was assessed by dynamic infusion cavernosometry. The corpora underwent
      histochemistry/immunohistochemistry with quantitative image analysis for
      SM/collagen ratio, collagen III/I ratio, alpha-SM actin, inducible nitric oxide
      synthase (iNOS), proliferating cell nuclear antigen, and terminal
      deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling
      as a marker of apoptosis. RESULTS: Compared with the sham group, the BCNX rats
      demonstrated CVOD as measured by the drop rate, a 60% reduction in the
      SM/collagen ratio, a twofold increase in iNOS expression, and a threefold
      increase in intracorporeal apoptosis. Compared with the BCNX group, vardenafil
      increased both iNOS and proliferating cell nuclear antigen expression (SM cell
      replication), with normalization of the dynamic infusion cavernosometry drop rate
      and SM/collagen ratio. CONCLUSIONS: Long-term treatment with vardenafil may
      prevent CVOD after radical prostatectomy by preserving SM content and inhibiting
      corporal fibrosis possibly by its effect on iNOS.

PMID- 16904480
TI  - Finasteride effects on hypoxia and angiogenetic markers in benign prostatic
      hyperplasia.
AB  - OBJECTIVES: To assess the effects of finasteride on angiogenetic and hypoxia
      markers in benign prostatic hyperplasia. METHODS: A total of 178 patients aged 51
      to 85 years (mean 68.7) with benign prostatic hyperplasia and awaiting
      transurethral prostate resection were prospectively randomized into a group of
      patients receiving finasteride (group 1; 88 patients) and a group of patients who
      received no medication until transurethral prostate resection (group 2; 90
      patients). Tissue specimens were immunohistochemically stained with monoclonal
      antibodies against CD34 for microvessel density (MVD), vascular endothelial
      growth factor (VEGF), and hypoxia inducible factor-1alpha (HIF-1alpha). RESULTS:
      Blood loss during transurethral prostate resection was significantly higher in
      group 2 compared with group 1 (P <0.001). The distribution of CD34 immunostaining
      was mainly at the suburethral prostate. MVD, VEGF, and HIF-1alpha values were
      significantly lower statistically (P <0.001) in group 1 compared with group 2. In
      the finasteride group (group 1), the positive correlation of the immunoreactivity
      of CD34 and HIF-1alpha, VEGF and HIF-1alpha, and VEGF and CD34 was statistically
      significant (P <0.001). In the same group, MVD and VEGF and HIF-1alpha expression
      correlated statistically with the treatment duration. CONCLUSIONS: Finasteride
      administration in benign prostatic hyperplasia results in statistically
      significant suppression of MVD, VEGF, and HIF-1alpha in a time-dependent manner.

PMID- 16904481
TI  - Effects of potassium channel modulators on human detrusor smooth muscle myogenic
      phasic contractile activity: potential therapeutic targets for overactive
      bladder.
AB  - OBJECTIVES: Increased urinary bladder detrusor smooth muscle phasic contractility
      has been suggested to be associated with idiopathic bladder overactivity (OAB).
      We examined the role of voltage-dependent L-type calcium channels, adenosine
      triphosphate-sensitive potassium (K(ATP)) channels, and calcium-activated
      potassium (BK(Ca) and SK(Ca)) channels in the regulation of human detrusor phasic
      contractile activity. METHODS: Isolated human bladder strip phasic contractions
      were measured and quantified as the mean area under the force-time curve,
      amplitude, and frequency of phasic contractions in 22 bladder samples. RESULTS:
      Human detrusor strips displayed myogenic phasic contractions in the presence of
      atropine (10(-6) M), phentolamine (10(-6) M), propranolol (10(-6) M), suramin
      (10(-5) M), and tetrodotoxin (10(-6) M). The L-type calcium channel inhibitor
      nifedipine (300 nM) abolished the contractile activity. Blockade of K(ATP)
      channels by glibenclamide (1 and 10 microM) did not alter myogenic contractions.
      In contrast, the K(ATP) channel opener pinacidil (10 microM) markedly inhibited
      phasic contractility. Iberiotoxin (100 nM) and apamin (100 nM), potent and
      selective inhibitors of BK(Ca) and SK(Ca) channels, respectively, significantly
      increased the area under the force-time curve and the amplitude of contractions.
      CONCLUSIONS: Phasic contractions of human detrusor are dependent on calcium entry
      through L-type calcium channels. BK(Ca) and SK(Ca) channels play a key role in
      the modulation of human detrusor smooth muscle phasic contractility. Furthermore,
      these observations support the concept that increasing conductance through
      K(ATP), BK(Ca), and SK(Ca) channels may represent attractive pharmacologic
      targets for decreasing phasic contractions of detrusor smooth muscle in OAB.

PMID- 16904482
TI  - Periurethral cellular injection: comparison of muscle-derived progenitor cells
      and fibroblasts with regard to efficacy and tissue contractility in an animal
      model of stress urinary incontinence.
AB  - OBJECTIVES: To compare muscle-derived cells (MDCs) and fibroblasts with regard to
      their potential for restoration of urethral function on injection in a previously
      established animal model of stress urinary incontinence. METHODS: The animals
      were divided into four (dosage) or five (cell concentration) experimental groups:
      normal, nontreated controls (normal group) or bilateral sciatic nerve transection
      with either periurethral injection of saline (saline group), MDCs (MDC group),
      fibroblasts (fibroblast group), or MDC/fibroblast mixture (mixed group). At 4
      weeks after injection, the leak point pressure (LPP) was measured and
      contractility testing and histologic analysis were performed. RESULTS: The
      histologic examination demonstrated muscular atrophy in the saline group and new
      striated muscle fibers at the sites of MDC injection in the MDC group, but not in
      the fibroblast group. Denervation of the urethra resulted in a significant
      decrease of maximal fast-twitch muscle contraction amplitude to only 9% of
      normal. MDC injection into the denervated urethra significantly improved the fast
      twitch muscle contraction amplitude to 73% of normal. The LPP of the normal,
      saline, MDC, fibroblast, and mixed groups at 4 weeks after treatment was 43.3 +/-
      2.5, 25.8 +/- 1.4, 38.2 +/- 4.2, 38.3 +/- 1.2, and 34.5 +/- 3.3 cm H2O,
      respectively. In the cell dosage experiment, the LPP increased with increases in
      the injected cell number. Evidence of obstruction was observed in the high-dose
      (1 x 10(7) cells) fibroblast group. CONCLUSIONS: Although both MDCs and
      fibroblast injection increased the LPP in a stress urinary incontinence rat
      model, only MDCs significantly improved urethral muscle strip contractility.
      Moreover, urinary retention developed with high-dose fibroblast injection, but
      not with MDC injection.

PMID- 16904483
TI  - Effects of CPU 86017 (chlorobenzyltetrahydroberberine chloride) and its
      enantiomers on thyrotoxicosis-induced overactive endothelin-1 system and
      oxidative stress in rat testes.
AB  - OBJECTIVES: To study the effects of CPU 86017, a berberine derivative, and its
      four enantiomers on thyrotoxicosis-induced oxidative stress and the excessive
      endothelin-1 system in rat testes. METHODS: Adult male SD rats were given high
      dose L-thyroxin (0.2 mg/kg subcutaneously) once daily for 10 days to develop
      thyrotoxicosis. Subsets of the rats were treated with CPU 86017 or its four
      enantiomers (SR, SS, RS, and RR) once daily from day 6 to day 10. The alterations
      of redox, nitric oxide synthase, and endothelin-1 system in testes were examined
      by spectrophotometry and reverse transcriptase-polymerase chain reaction assay.
      RESULTS: After 10 days of high-dose L-thyroxin administration, increased mRNA
      expression of prepro-endothelin-1 and endothelin-converting enzyme was observed
      in the rat testes, accompanied by an elevated inducible nitric oxide synthase
      activity and oxidative stress. CPU 86017 and its enantiomer SR significantly
      improved these abnormalities. CONCLUSIONS: High-dose L-thyroxin results in an
      overactive endothelin-1 system and oxidative stress in adult rat testis. CPU
      86017 and its enantiomer SR suppressed the excessive ET-1 system by improving
      oxidative stress, and SR exhibited more potent efficacy than CPU 86017 and other
      enantiomers.

PMID- 16904484
TI  - Talkin' 'bout synthetic generation.

PMID- 16904487
TI  - Chiropractic patients in Denmark 2002: an expanded description and comparison
      with 1999 survey.
AB  - OBJECTIVE: The purpose of this study is to provide an expanded description of
      Danish chiropractic patients and to compare characteristics seen in a survey from
      1999 with those seen in 2002. METHODS: All chiropractic clinics in Denmark were
      asked to collect information on new patients during 1 randomly assigned week in
      2002 using a survey questionnaire. All 52 weeks of the year 2002 were represented
      with an even dispersion of weeks (182 clinics participated). Outcome measures
      included age, sex, education, occupation, location and duration of chief
      complaint, pain intensity, limitation of activities of daily living, mode of
      referral, duration of sick leave, previous treatments, comorbidity, SF-12,
      smoking habits, and use of x-ray. RESULTS: Eighty-five percent of all
      chiropractic clinics in Denmark participated in the study, and 1595 patients
      (81%) filled out a self-administered questionnaire. As in 1999, the most frequent
      area of complaint was pain related to the lower back and pelvis (49%). Contrary
      to the 1999 survey, most of the patients (64%) had complaints of less than 4
      weeks of duration. Twenty-nine percent of the patients had been off work because
      of their symptoms; most of these for less than 1 week. Fifty-one percent of all
      patients were referred to chiropractors in 2002 (doubling since 1999). Referrals
      from general medical practitioners rose from 11% in 1999 to 17% in 2002. Sixty
      percent of all patients had similar symptoms in the past, and approximately half
      had previously received treatment of the same or a similar problem. Thirty
      percent of first-time chiropractic patients were x-rayed. Compared with general
      population measures, Danish chiropractic patients had significantly worse
      physical health status measured by the SF-12. CONCLUSIONS: Most Danish
      chiropractic patients complain of pain related to the spine, especially the lower
      back, with duration of symptoms of less than 4 weeks, and many with recurrent
      back pain. Referrals from general medical practitioners have increased since
      1999.

PMID- 16904488
TI  - Three-dimensional vertebral motions produced by mechanical force spinal
      manipulation.
AB  - OBJECTIVE: The aim of this study was to quantify and compare the 3-dimensional
      intersegmental motion responses produced by 3 commonly used chiropractic
      adjusting instruments. METHODS: Six adolescent Merino sheep were examined at the
      Institute for Medical and Veterinary Science, Adelaide, Australia. In all
      animals, triaxial accelerometers were attached to intraosseous pins rigidly fixed
      to the L1 and L2 spinous processes under fluoroscopic guidance. Three handheld
      mechanical force chiropractic adjusting instruments (Chiropractic Adjusting Tool
      [CAT], Activator Adjusting Instrument IV [Activator IV], and the Impulse
      Adjusting Instrument [Impulse]) were used to randomly apply posteroanterior (PA)
      spinal manipulative thrusts to the spinous process of T12. Three force settings
      (low, medium, and high) and a fourth setting (Activator IV only) were applied in
      a randomized repeated measures design. Acceleration responses in adjacent
      segments (L1 and L2) were recorded at 5 kHz. The multiaxial intersegmental (L1
      L2) acceleration and displacement response at each force setting was computed and
      compared among the 3 devices using a repeated measures analysis of variance
      (alpha = .05). RESULTS: For all devices, intersegmental motion responses were
      greatest for axial, followed by PA and medial-lateral (ML) measurement axes for
      the data examined. Displacements ranged from 0.11 mm (ML axis, Activator IV low
      setting) to 1.76 mm (PA axis, Impulse high setting). Compared with the mechanical
      (spring) adjusting instruments (CAT, Activator IV), the electromechanical Impulse
      produced the most linear increase in both force and intersegmental motion
      response and resulted in the greatest acceleration and displacement responses
      (high setting). Significantly larger magnitude intersegmental motion responses
      were observed for Activator IV vs CAT at the medium and high settings (P < .05).
      Significantly larger-magnitude PA intersegmental acceleration and displacement
      responses were consistently observed for Impulse compared with Activator IV and
      CAT for the high force setting (P < .05). CONCLUSIONS: Larger-magnitude, 3D
      intersegmental displacement and acceleration responses were observed for spinal
      manipulative thrusts delivered with Impulse at most force settings and always at
      the high force setting. Our results indicate that the force-time characteristics
      of impulsive-type adjusting instruments significantly affects spinal motion and
      suggests that instruments can and should be tuned to provide optimal force
      delivery.

PMID- 16904489
TI  - The electromyographic activity of thoracic paraspinal muscles identified as
      abnormal with palpation.
AB  - OBJECTIVE: The aim of this study was to compare the electromyographic (EMG)
      activity of deep muscles in the thoracic paravertebral gutter (PVG) detected as
      abnormal to palpation (AbPT) and reported as tender by the subject with muscles
      underlying nontender (NT), normal to palpation sites under various experimental
      conditions. METHODS: Twelve subjects (mean age, 25.42 years; range, 22-43 years)
      participated in this study. Fine-wire, bipolar intramuscular electrodes were
      inserted, under real-time ultrasonic guidance, into the deep paravertebral muscle
      mass underlying 1 AbPT and 2 NT sites (1 segment above and below the AbPT site)
      in the thoracic PVG regions. Electromyographic activity was recorded under the
      following conditions: resting prone, prone active trunk extension, application of
      pressure (300 kPa) to adjacent spinous processes, resting seated, passive and
      active seated trunk rotation, and supporting 2-kg weights in outstretched arms.
      RESULTS: Mean EMG activity was highest at the AbPT site, relative to NT sites,
      under all conditions, with a significant between-group effect of site (F2,31 =
      4.13, P = .03) and large between-group effect size (eta2 = 0.21). There was also
      a trend for lower percentage change from baseline resting at the AbPT sites,
      relative to the NT sites, in response to the demand of other conditions. There
      were large variations in EMG activity within and between individuals, and large
      SDs accompanied the mean values of EMG activity in all cases. CONCLUSION:
      Increased motor activity may be a contributing factor to tissue changes in the
      PVG detected with palpation. However, caution must be used when interpreting
      these results because of the large variations, small sample size, and issues
      associated with EMG normalization.

PMID- 16904491
TI  - Factors associated with patient satisfaction with chiropractic care: survey and
      review of the literature.
AB  - OBJECTIVE: The purpose of this study is to review the recent literature on
      satisfaction with chiropractic care and offer a multivariate analysis of a
      national household survey data to understand which aspects of care and behavior
      contribute most to patient satisfaction with chiropractors. METHODS: A national
      phone survey of households was done to measure attitudes, utilization, and health
      practices of chiropractic users and nonusers. A 73% response rate was achieved.
      Satisfaction with chiropractic services is analyzed using both descriptive and
      multivariate methods. RESULTS: Satisfaction levels with chiropractic care are
      quite high (83% of persons are satisfied or very satisfied). High satisfaction is
      related to several factors, including whether the chiropractor orders and
      interprets laboratory tests, whether the chiropractor displays concern about
      patient's overall health, and the extent to which the chiropractor explains the
      condition and the treatment. CONCLUSIONS: The evidence about the factors that
      underlie high levels of chiropractic satisfaction is not consistent.
      Communication quality seems to be a consistent predictor of patient satisfaction
      with chiropractors. More research is needed to understand the role of perceived
      effectiveness of treatment, intensity of use, accessibility, and financing issues
      in determining patient satisfaction levels.

PMID- 16904490
TI  - Chiropractic consultation requests in the Veterans Affairs Health Care System:
      demographic characteristics of the initial 100 patients at the Western New York
      medical center.
AB  - OBJECTIVES: The objectives of this study were to review the demographic
      characteristics of Veterans Affairs (VA) chiropractic patients and to determine
      the level of appropriateness of chiropractic consultation requests within a VA
      chiropractic clinic. Information regarding the volume of requests and wait times
      for appointments were obtained to provide insight on the demand for and access to
      VA chiropractic services. METHODS: A purposive sample of the first 100
      chiropractic consultation requests received through the Computerized Patient
      Record System at the VA of Western New York Health Care System was selected for
      data collection and analysis. RESULTS: The VA chiropractic patients in this study
      were primarily older men with chronic low-back pain that had not responded to
      medical management and other treatment modalities. More than half of the patients
      had service-connected disabilities. Consultation requests came largely from
      primary care, and most requests were for patients for whom chiropractic was
      clinically indicated and requested preconsultation diagnostic studies had been
      performed. CONCLUSIONS: The VA chiropractic patients in this study differed from
      traditional non-VA chiropractic patients with regard to age and sex. A review of
      the chiropractic consultation requests that were considered inappropriate
      resulted in a revision of the instructions for requesting providers within the
      Computerized Patient Record System. Additional health systems research is
      indicated to evaluate chiropractic implementation on a larger scale within the VA
      Health Care System.

PMID- 16904492
TI  - Applying generalizability theory to high-stakes objective structured clinical
      examinations in a naturalistic environment.
AB  - PURPOSE: The purpose of this project was to determine if generalizability theory
      could be successfully applied to a high-stakes licensure objective structured
      clinical examination as part of its normal administrative procedures and whether
      the analysis could yield useful information with regard to sources of variance.
      METHODS: The anonymized data received from the Canadian Chiropractic Examining
      Board for its June 2005 Clinical Skills Examination were analyzed with
      generalizability theory. Variance components were estimated with SPSS 11.5 (SPSS
      Inc, Chicago, Ill) as partially nested data. The data included 182 candidates, 43
      raters, 40 standardized patient actors, and 18 individual cases. RESULTS:
      Internal consistency estimates (Cronbach alpha) were .86 for day 1 and .91 for
      day 2. The alpha estimates for stations averaged .68 for day 1 and .74 for day 2.
      The generalizability-coefficient for the day 1 exam was .65 and for the day 2 was
      .42. G-coefficients for stations averaged .63 for day 1 and .74 for day 2. On day
      1, the raters contributed 7% of the variance, and on day 2, the raters
      contributed 8%. CONCLUSIONS: Generalizability theory can contribute to the
      understanding of sources of variance and provide direction for the improvement of
      individual stations. The size of the rater variance in a station may also
      indicate the need for increased training in that station or the need to make the
      scoring checklist more clear and definitive. Generalizability theory, however,
      must be cautiously applied, and it requires careful selection of the floating
      raters and vigorous training of the raters in each station.

PMID- 16904493
TI  - Digitized infrared segmental thermometry: time requirements for stable
      recordings.
AB  - OBJECTIVES: Digitized infrared segmental thermometry (DIST) is a method for
      measuring and recording skin surface body temperatures. The project evaluated the
      required length of time for patients to acclimatize their core body temperature
      to ambient conditions to obtain stable DIST readings. METHODS: Seventeen subjects
      were allowed a 20-minute acclimatizing period in a temperature-controlled room.
      The bilateral DIST temperature was measured with thermistors in combination with
      infrared cameras (IRCs) at the C4 and L4 levels. All IRC temperatures were
      recorded after a 20-minute stabilization period. The room temperature and
      relative humidity were recorded throughout all trials. The acclimatization trend
      was computed from the 20- to 24-minute period for the IRCs, and the
      acclimatization trend was computed continuously for a total of 30 minutes (at 2
      minute intervals) for 5 days. RESULTS: We discovered a stabilization trend in the
      early trial stages, with the thermistor recordings between 8 and 16 minutes. The
      IRC trend was also conclusive for the core temperature requirements. CONCLUSIONS:
      This study determined a core body temperature acclimatization trend tested among
      patients using thermistor recordings in a controlled environment. Based on these
      findings, we recommend acclimatization in a temperature- and humidity-controlled
      environment for a minimum 8-minute period, followed by an 8-minute maximum
      recording period with the patient in a prone position to obtain accurate DIST
      recordings.

PMID- 16904494
TI  - Chiropractic management of cow's milk protein intolerance in infants with sleep
      dysfunction syndrome: a therapeutic trial.
AB  - OBJECTIVE: In addition to the more usual cutaneous, gastrointestinal, and
      respiratory problems, infants with cow's milk intolerance (CMI) may present with
      a disturbed sleep pattern. Frustrated mothers may turn to their doctor of
      chiropractic for assistance. This pilot study shows how a therapeutic trial may
      offer a realistic, noninvasive approach to the chiropractic management of infants
      with this clinical problem. METHODS: A pilot study to describe the presentation
      and treatment of infants presenting with disturbed sleep patterns to a
      chiropractic clinic was undertaken. Infants fulfilling a clinical screening
      protocol for CMI were selected for a therapeutic trial. The sleep behavior of
      subjects was monitored over a 4-week period during which they were managed by
      dietary change and a high-impulse, low-amplitude whole-of-body chiropractic
      management protocol. RESULTS: Fifty-nine infants presented with disturbed sleep.
      Of these, 19 met the clinical criteria used to establish the diagnosis CMI. The
      mothers of breast-fed infants were counseled on how to implement a dairy-free
      diet, and those infants who were artificially fed were changed from cow's milk
      based formulae to either a partially or wholly hydrolyzed formula. Fourteen
      achieved a stable sleep pattern within the study period. In 5 instances, the
      sleep pattern remained problematic, but other clinical evidence of
      hypersensitivity reactions attributable to CMI disappeared. By the end of the
      study, no subject had demonstrable evidence of either biomechanical derangement
      or functional neurologic imbalance. CONCLUSION: CMI should be considered as a
      possibility in infants with disturbed sleep patterns who present for chiropractic
      care. This study describes how a therapeutic trial involving dietary
      modification, parental counseling, and comprehensive chiropractic care may offer
      a noninvasive approach to excluding and/or managing this condition. Further
      research is required before definitive recommendations can be made.

PMID- 16904495
TI  - Manual examination of the spine: a systematic critical literature review of
      reproducibility.
AB  - OBJECTIVE: Poor reproducibility of spinal palpation has been reported in
      previously published literature, and authors of recent reviews have posted
      criticism on study quality. This article critically analyzes the literature
      pertaining to the inter- and intraobserver reproducibility of spinal palpation to
      investigate the consistency of study results and assess the level of evidence for
      reproducibility. METHODS: Systematic review and meta-analysis were performed on
      relevant literature published from 1965 to 2005, identified using the electronic
      databases MEDLINE, MANTIS, and CINAHL and checking of reference lists.
      Descriptive data from included articles were extracted independently by 2
      reviewers. A 6-point scale was constructed to assess the methodological quality
      of original studies. A meta-analysis was conducted among the high-quality studies
      to investigate the consistency of data, separately on motion palpation, static
      palpation, osseous pain, soft tissue pain, soft tissue changes, and global
      assessment. A standardized method was used to determine the level of evidence.
      RESULTS: The quality score of 48 included studies ranged from 0% to 100%. There
      was strong evidence that the interobserver reproducibility of osseous and soft
      tissue pain is clinically acceptable (kappa > or = 0.4) and that intraobserver
      reproducibility of soft tissue pain and global assessment are clinically
      acceptable. Other spinal procedures are either not reproducible or the evidence
      is conflicting or preliminary.

PMID- 16904496
TI  - Diagnosis and management of posttraumatic piriformis syndrome: a case study.
AB  - OBJECTIVE: The aim of this study is to describe the clinical management of a
      young male patient with sciatica symptoms that developed after an avulsion of the
      ischial tuberosity. This is a rare injury, but complications may occur. CLINICAL
      FEATURE: A 19-year-old patient developed sciatica 6 months after a football
      injury. The patient described his symptoms as a shooting pain from the buttock to
      the lateral part of the foot, along the back of his thigh and calf, sometimes
      accompanied by paresthesia. Physical examination showed restricted hip range of
      motion and a positive Bonnet's test. X-ray analysis revealed a bony overgrowth of
      the right ischial tuberosity. INTERVENTION AND OUTCOME: A treatment plan was
      designed to decrease the pain level, increase sacroiliac and lumbar joint
      mobility, and augment muscular extensibility. The patient received 20 treatments
      over a period of approximately 3 months. Complete recovery was observed 5 months
      later. CONCLUSION: Although many differential diagnoses were contemplated, it is
      most likely that changes in muscular tension and gait pattern, resulting from the
      ischial tuberosity avulsion, contributed to overuse of the piriformis muscle
      leading to a piriformis syndrome.

PMID- 16904497
TI  - Cauda equina syndrome after epidural steroid injection: a case report.
AB  - OBJECTIVE: Conventional treatment methods of lumbusacral radiculopathy are
      physical therapy, epidural steroid injections, oral medications, and spinal
      manipulative therapy. Cauda equina syndrome is a rare complication of epidural
      anesthesia. The following case is a report of cauda equina syndrome possibly
      caused by epidural injection of triamcinolone and bupivacaine. CLINICAL FEATURES:
      A 50-year-old woman with low back and right leg pain was scheduled for epidural
      steroid injection. INTERVENTION AND OUTCOME: An 18-gauge Touhy needle was
      inserted until loss of resistance occurred at the L4-5 level. Spread of the
      contrast medium within the epidural space was determined by radiographic imaging.
      After verifying the epidural space, bupivacaine and triamcinolone diacetate were
      injected. After the injection, there was a reduction in radicular symptoms. Three
      hours later, she complained of perineal numbness and lower extremity weakness.
      The neurologic evaluation revealed loss of sensation in the saddle area and
      medial aspect of her right leg. There was a decrease in the perception of
      pinprick test. Deep-tendon reflexes were decreased especially in the right leg.
      She was unable to urinate. The patient's symptoms improved slightly over the next
      few hours. She had a gradual return of motor function and ability of feeling
      Foley catheter. All of the symptoms were completely resolved over the next 8
      hours. CONCLUSION: Complications associated with epidural steroid injections are
      rare. Clinical examination and continued vigilance for neurologic deterioration
      after epidural steroid injections is important.

PMID- 16904498
TI  - Commentary: differential diagnosis of fibromyalgia syndrome: proposal of a model
      and algorithm for patients presenting with the primary symptom of chronic
      widespread pain.

PMID- 16904500
TI  - The efficiency of multiple impulse therapy for musculoskeletal complaints.

PMID- 16904502
TI  - Psychiatry malpractice and administrative inquiries of alleged physician
      misconduct.
AB  - Practicing psychiatrists face a range of professional liability from malpractice
      litigation and from inquiries and hearings conducted by health care agencies. The
      causes of an action and the standards by which physician conduct is measured vary
      widely between these two processes. Many psychiatrists do not appreciate
      sufficiently the gravity of the risks they may face from an administrative
      sanction. Understanding the legal and administrative expectations of practicing
      psychiatrists serves practitioners' professional risk management. Those
      psychiatrists who choose to participate as expert witnesses for courts or
      administrative agencies need to familiarize themselves with the applicable legal
      standards and the respective roles of experts in these two different settings.
      The courts and administrative agencies have different social missions and
      correspondingly differing expectations of the expert opinions admitted.An
      expert's function as educator about the application of psychiatric knowledge and
      treatments to legal contexts is optimized when that expert clearly understands
      the function of the opinion that is sought. As educators about special knowledge
      to the adjudicating body, experts are advocates for their objectively generated
      and scientifically grounded opinion. Psychiatry is increasingly under the purview
      of regulations from multiple sources private and public. This article has
      reviewed medicolegal concepts and terms of psychiatrists' exposure to liability
      from a comparative point of view. Familiarity assists psychiatrists in navigating
      the complex legal arena in which they practice and provides a foundation for
      psychiatrists to work to change the multitude of laws and regulations when doing
      so is in the best interests of their patients and of their discipline of
      medicine.

PMID- 16904503
TI  - The detection of malingered post-traumatic stress disorder.
AB  - The detection of malingered PTSD is made particularly challenging by the
      subjective nature of PTSD criteria and requires a thorough, systematic approach.
      The psychiatrist must gather and analyze evidence from the evaluation, clinical
      records, psychologic testing, third parties, and other sources. Although some
      individuals may malinger PTSD to avoid criminal sanctions, the most common
      motivation for malingering PTSD is financial gain. Clinical nuances may help
      distinguish genuine from malingered PTSD. The psychiatrist should be aware of the
      differences observed between civilian and combat-related PTSD. Although special
      effort is required, the psychiatrist bears considerable responsibility to assist
      society in differentiating true PTSD from malingering.Undetected malingering is
      not limited simply to fraudulent monetary awards, but can involve misuse of
      limited mental health resources, leading to negative consequences for the mental
      health system. As Burkett aptly notes, malingered combat PTSD cases "take time,
      energy, and financial resources away from treating true combat veterans with
      PTSD. And real combat vets who truly need help end up in group therapy with
      phonies, get disgusted, and quit treatment".

PMID- 16904504
TI  - Substance misuse and substance-related disorders in forensic psychiatry.
AB  - There is a broad range of substance-related problems that arise for the forensic
      psychiatrist. For many, what is most challenging about addressing these issues
      are the complex behavioral, biological, clinical, and social phenomena involved.
      Substance- related illnesses are on the cutting edge of brain research. Substance
      related behavior that brings individuals to the attention of forensic
      psychiatrists involves a wide spectrum of substance use patterns, but even
      substance misuse may have profound and relevant effects, forensically. The social
      forces that mold our laws and attitudes toward addictive drug use are at work in
      almost every forensic context. Substance-related issues provide a rich medium for
      the application of forensic psychiatric principles and practice. As in all of
      forensic psychiatric work, the psychiatrist should be familiar with each forensic
      context in which addiction issues arise. They should become familiar with the
      relevant definitions, criteria, and legal requirements that apply in each
      specific area of their practice, rather than assume that clinical definitions and
      clinical reasoning will carry them. Comfort and effectiveness with addiction
      issues requires willingness to continually educate oneself about this rapidly
      changing field, and familiarity with one's own attitudes and beliefs regarding
      addictive illness.

PMID- 16904505
TI  - Psychiatric fitness-for-duty evaluations.
AB  - Fitness-for-duty examinations are a common type of psychiatric disability
      evaluation. These evaluations are typically best performed by the independent
      (nontreating) psychiatrist with forensic training or expertise in these
      examinations. A comprehensive evaluation requires careful definition of the
      referral questions and consideration of the terms of the referral; review of
      relevant job-specific documentation and medical records; the collection of
      collateral information from relevant third-party informants; a thorough clinical
      psychiatric examination; and possibly additional testing. The examination report
      needs to be comprehensive, address the specific questions in clear language
      understandable to the non-mental health clinician, and use all available data to
      substantiate the logical conclusions in a fair, accurate, and objective manner.

PMID- 16904506
TI  - Psychiatry and the military: an update.
AB  - The United States has historically been concerned about the successful adjustment
      of its military members returning from war. These concerns are based on the
      recognition that war-zone exposures may have considerable negative emotional or
      behavior consequences. As the global war on terror continues, the United States
      military medical system will be required to address issues at the interface of
      psychiatry and the law. Despite clinical advances within the theater of war and
      at tertiary facilities in the United States, some military members will develop
      chronic and disabling mental illness as a result of traumatic exposure and
      exacerbated by the demands of the austere and dangerous operational environment.
      The extent to which violent and aggressive behavior in the aftermath of
      deployment can be attributed to combat experience remains an area of debate and
      ongoing investigation. However, experience suggests that a very small subgroup of
      the hundreds of thousands of war veterans deployed in conjunction with the
      current conflict in Iraq has already been involved in violent crimes. For this
      group, military forensic psychiatrists will be called on to make determinations
      of competency and criminal responsibility and to inform the courts about the
      potential contributions of war-related distress or disorder to criminal behavior.
      Though the overwhelming majority of war veterans will not be involved in criminal
      proceedings, a minority will develop career-ending (and in rare instances, life
      ending) disabilities as a result of mental illness. For those who are no longer
      fit for duty, the military Physical Disability Evaluation System must make
      determinations of the extent to which future military performance and future
      civilian social and occupational function have been compromised. For a small yet
      highly visible minority of returning veterans, questions about the cause,
      precipitants, and manner of death will necessitate psychological autopsies. This
      article highlighted recent updates in military forensic psychiatry and the
      mechanisms through which answers to questions of disability and criminal
      culpability, and motivation underpinning self-injurious behavior, are determined
      within the United States military. As the global war on terror progresses,
      further experience and study of our country's judicial processes, disability
      system, and the policies and procedures governing psychological autopsies must
      evolve to meet these increasing demands.

PMID- 16904507
TI  - Psychopathy: a clinical and forensic overview.
AB  - There is a substantial amount of empirical evidence that psychopathy, as measured
      by the PCL-R and its derivatives, is a predictor of recidivism and violence in
      prison, forensic psychiatric, and civil psychiatric populations. The PCL-R is one
      of the most generalizable of the risk factors identified thus far, and for this
      reason it is included in various actuarial and structured clinical risk
      assessment procedures. Although psychopathy is not the only risk factor for
      recidivism and violence, it is too important to ignore, particularly with respect
      to violence. Treatment and management are difficult, time-consuming, and
      expensive, but new initiatives based on current theory and research on
      psychopathy and the most effective correctional philosophies may help to reduce
      the harm done by psychopaths.

PMID- 16904508
TI  - An overview of juveniles and school violence.
AB  - Despite the relative rarity of school shootings, targeted violence, and school
      associated violent deaths, any youth who presents with words, gestures, or
      actions of a threatening or violent nature in a school setting should be assessed
      and referred for further evaluation by a mental health professional and, if
      clinically indicated, a forensic evaluator.The request for a juvenile risk
      assessment for future dangerousness requires careful delineation of role and
      agency; confidentiality issues; a comprehensive diagnostic evaluation of the
      youth; and a detailed assessment of the youth's perceived threat or problematic
      behavior. Various protective and risk factors and consideration of other
      individual, family, school/peer, and situational factors should also be
      explored.There is still much information that is unknown when considering school
      violence or targeted school violence. There is clearly a need for additional
      research on the identification of at-risk youths, the contributions and
      significance of various protective and risk factors, the impact of peer
      relationships, and perceived rejection, socioeconomic status, subtypes of
      aggression, and developmental stages. Examples of future research direction might
      include difference by gender, presence of affective or psychotic disorders,
      substance abuse, emerging characterologic disturbances, and physiologic markers,
      such as cortisol or serotonin. Additional research regarding best practices and
      the development of clinical guidelines or practice parameters is also needed.

PMID- 16904509
TI  - Forensic psychiatric aspects of inpatient violence.
AB  - Inpatient aggression jeopardizes the safety of psychiatric clinicians and
      patients. A minority of psychiatric inpatients is responsible for most of
      inpatient assaults; this subset of repetitively assaultive patients warrants
      greater attention in the form of systematic study. In developing treatment
      approaches for assaultive inpatients, it is important to characterize the primary
      motivation driving aggressive behavior. There are many pharmacologic agents and
      psychotherapeutic approaches available to address inpatients who engage in
      impulsive and psychotic violence, but the treatment of inpatients with antisocial
      or psychopathy personality remain limited, and further study is needed. To
      protect the safety of patients and staff, criminal prosecution of inpatient
      assaults is clinically justified if an assailant continues to be aggressive
      despite appropriate clinical interventions or commits an act of planned
      aggression so egregious that prosecution is the only reasonable alternative.

PMID- 16904510
TI  - An overview of correctional psychiatry.
AB  - Supermax facilities may be an unfortunate and unpleasant necessity in modern
      corrections. Because of the serious dangers posed by prison gangs, they are
      unlikely to disappear completely from the correctional landscape any time soon.
      But such units should be carefully reserved for those inmates who pose the most
      serious danger to the prison environment. Further, the constitutional duty to
      provide medical and mental health care does not end at the supermax door. There
      is a great deal of common ground between the opponents of such environments and
      those who view them as a necessity. No one should want these expensive beds to be
      used for people who could be more therapeutically and safely managed in mental
      health treatment environments. No one should want people with serious mental
      illnesses to be punished for their symptoms. Finally, no one wants these units to
      make people more, instead of less, dangerous. It is in everyone's interests to
      learn as much as possible about the potential of these units for good and for
      harm. Corrections is a profession, and professions base their practices on data.
      If we are to avoid the most egregious and harmful effects of supermax
      confinement, we need to understand them far better than we currently do. Though
      there is a role for advocacy from those supporting or opposed to such
      environments, there is also a need for objective, scientifically rigorous study
      of these units and the people who live there.

PMID- 16904511
TI  - Treating incarcerated women: gender matters.
AB  - Research on incarcerated women has shown they have a high degree of comorbid
      psychopathology, including substance dependence, posttraumatic stress disorder
      (PTSD), antisocial personality disorder (ASPD), and major depression.
      Incarcerated women differ from their community peers by having more symptoms
      related to addiction, ASPD, and PTSD. At the same time, incarcerated women are
      every bit as likely as incarcerated men to be dependent on drugs and almost as
      likely to be dependent on alcohol. What emerges is a picture of the incarcerated
      woman far more likely to have had traumatic experiences, including early sexual
      and physical abuse, than her male peers but every bit as likely to have substance
      dependence and, in some correctional populations (eg, sentenced felons),
      antisocial personality disorder. Central to the discussion of how best to treat
      female offenders is the need to address how programs would best be structured for
      women with severe substance dependence, substantial trauma histories, and
      personality pathology, including ASPD. Incarcerated women are a population with
      complex medical and mental health needs and are likely to be high users of
      services within the correctional system. This poses challenges to a system
      already stretched thin in caring for these complex inmates. This article
      emphasizes that gender differences need to be appreciated, and that service
      delivery to male and female inmates needs to be structured with gender in mind.
      The article recommends case management, treatment in highly structured
      therapeutic communities, and emphasizing abstinence from substances and
      development of skill sets to engage in healthy relationships.A major future
      challenge lies in researching treatment interventions for women in the
      correctional system. There are few existing trials of treatment efficacy and, as
      previously noted, the incarcerated female population differs from populations of
      incarcerated men and women in the community. Opiate-dependent women undergoing
      treatment in the community may prove to be a reasonable comparison group in
      beginning to develop evidence-based treatment for female offenders in prisons and
      jails. Ultimately, the development of services for incarcerated women will
      consider gender, race, and psychopathology in determining treatment setting and
      modalities. We are on new ground. It is a promising and exciting time to be
      involved with treatment of female offenders.

PMID- 16904512
TI  - Psychiatry and the death penalty.
AB  - Psychiatrists conducting forensic evaluations of defendants facing a potential
      death penalty must understand the legal and ethical parameters governing these
      assessments in addition to the important clinical issues. Important areas to
      review with each defendant include the role of the evaluator, the party
      requesting the evaluation, circumstances in which the evaluation is not
      confidential, the nature, scope, and purpose of the evaluation, and the parties
      to whom the results of the evaluation are to be forwarded. In those circumstances
      in which the defense attorney has not retained the psychiatrist, the defendant's
      attorney must be aware that an evaluation has been ordered by the court or
      requested by the prosecution. The psychiatrist also must be prepared for
      passionate challenges to their findings from the defense or prosecution and in
      some instances for vigorous attacks on their own personal ethics. To weather such
      storms, the mental health evaluator must base their opinion on objective evidence
      rather than letting any personal bias guide their assessment.

PMID- 16904513
TI  - The psychological autopsy: solving the mysteries of death.
AB  - The psychological autopsy is an important assessment tool used to identify
      aspects of a person's life that explain any lingering mystery that shrouds their
      death. In addition to answering questions of the past, the psychological autopsy
      has significant implications for the future. Statistics obtained from mortality
      data affect the course of health care research, the flow of resources, and
      ultimately public health policy. From a public health perspective, the
      misclassification of suicides as accidents or deaths from natural causes can
      negatively affect research funding and policy development related to suicide
      prevention efforts, making a standardized and accurate procedure imperative.
      Although the psychological autopsy was developed initially as a tool to assist
      the coroner in clarifying the cause of death, this procedure has transcended the
      confines of forensic science and has applications in the many arenas of
      litigation and public health policy.

PMID- 16904514
TI  - Psychiatric expert witnesses in the new millennium.
AB  - We may anticipate changes in who is the expert in terms of gender, ethnicity, and
      professional discipline. We anticipate elaboration of training approaches. We
      foresee emergence of the "forensic tutor" role. We expect expansion of expert
      roles outside the courtroom. We expect demands for more constraint of expert
      roles, increased rigor, and empiric support. We expect vast expansion of
      technologic approaches to assessment and presentation. We expect evolution of
      ethical issues with preservation of core forensic values but changes in
      confidentiality, due process, and the nature of assessments. We expect extreme
      expansion of hard sciences in relation to understanding psychopathology.

PMID- 16904515
TI  - Interpretation of molecular marker data in the modern era.

PMID- 16904516
TI  - Six year experience of external beam radiotherapy, brachytherapy boost with a 1Ci
      (192)Ir source, and neoadjuvant hormonal manipulation for prostate cancer.
AB  - PURPOSE: To present preliminary outcomes of pulsed dose rate brachytherapy (PDR
      BT), external beam radiotherapy (EBRT), and hormonal manipulation, for prostate
      cancer. PATIENTS AND METHODS: Between December 1999 and January 2005, 165
      consecutive patients with Stage T1-T3, N0, M0 prostate cancer were treated.
      Hormones were used in every patient. Median follow-up was 36 months. Risk groups
      were low (either Stage < or =T2a, +/- Gleason score < or =6, +/- Prostate
      Specific Antigen [PSA] level < or =10 ng/mL); intermediate (either Stage T2b,c,
      +/- Gleason score 7, +/- PSA 10-20 ng/mL); and high (either Stage T3, +/- Gleason
      score 8-10, +/- PSA >20 ng/mL). RESULTS: At 3 years, Radiotherapy Oncology Group
      (RTOG) Grade 3 and 4 genito-urinary toxicity was 4% and 1.4%; RTOG Grade 3 and 4
      gastro-intestinal toxicity was 2.6% and 0%, respectively. Erectile preservation
      was 61%. Overall survival was 93% (154 of 165) and cause-specific survival was
      98% (162 of 165). At 3 years, disease free survival (DFS) was 93% (153 of 165).
      DFS for low-, intermediate-, and high-risk groups was 100%, 97%, and 81%,
      respectively (chi(2) (2) = 16.02, p = 0.0003). The nadir plus 2 ng/mL definition
      (chi(2) (2) = 14.49, p = 0.0007) best predicted clinical failure, having the
      lowest false-positive rate (3 of 165). The nadir plus 2 ng/mL PSA-progression
      free survival (PSA-PFS) rate was 100%, 95%, and 87% for the low-, intermediate,
      and high-risk groups, respectively. Overall ASTRO PSA-PFS rate was 88%.
      CONCLUSIONS: Pulsed dose rate brachytherapy plus EBRT is effective in treating
      localized prostate cancer, with acceptable toxicity. However, a median 5-year PSA
      PFS follow-up is required before providing a solid recommendation. This
      preliminary information supports continued use.

PMID- 16904517
TI  - Comparison of outcomes for patients with medically inoperable Stage I non-small
      cell lung cancer treated with two-dimensional vs. three-dimensional radiotherapy.
AB  - PURPOSE: This retrospective analysis was performed to assess the outcomes of
      three-dimensional (3D) conformal radiotherapy and two-dimensional (2D) planning.
      METHODS AND MATERIALS: Between 1978 and 2003, 200 patients with Stage I non-small
      cell lung cancer (NSCLC) were treated with radiotherapy alone at M.D. Anderson
      Cancer Center. Eighty-five patients were treated with 3D conformal radiotherapy.
      For the 3D group, median age, radiation dose, and follow-up was 73 (range, 50
      92), 66 Gy (range, 45-90.3 Gy), and 19 months (range, 3-77 months), respectively;
      and for the 2D group, 69 (range, 44-88), 64 Gy (range, 20-74 Gy), 20 months
      (range, 1-173 months), respectively. Overall survival (OS), disease-specific
      survival (DSS), disease-free survival (DFS), locoregional control (LRC), and
      distant metastasis-free survival (DMFS) rates were analyzed. RESULTS: There was
      no statistically significant difference in patient and tumor characteristics
      between 2D and 3D groups, except the 3D patients were older (p = 0.006). The OS,
      DSS, and LRC rates were significantly higher in patients who were treated by 3D
      conformal radiotherapy. Two- and 5-year OS for the 3D group were 68% and 36%,
      respectively, and 47% and 10% in the 2D group (p = 0.001). DSS at 2 and 5 years
      for the 3D group were 83% and 68%, respectively, vs. 62% and 29% in the 2D group
      (p < 0.001). LRC rates at 2 and 5 years for patients in the 3D group were 77% and
      70% and 53% and 34% in the 2D group (p < 0.001). On univariate analysis elective,
      nodal irradiation was associated with decreased OS, DSS, and LRC. On multivariate
      analysis, 3D conformal radiotherapy was associated with increased OS and DSS.
      Male sex, age > or =70, weight loss > or =5%, and tumor size > or =4 cm were
      associated with decreased OS and DSS. CONCLUSIONS: This study demonstrates that
      3D conformal radiotherapy improves outcomes in patients with medically inoperable
      Stage I NSCLC compared with 2D treatment and is an acceptable treatment for this
      group of patients.

PMID- 16904518
TI  - Final results of a Phase I/II dose escalation trial in non-small-cell lung cancer
      using three-dimensional conformal radiotherapy.
AB  - PURPOSE: The aim of this study was to determine the maximum tolerated dose (MTD)
      delivered within 6 weeks in patients with non-small-cell lung cancer (NSCLC). The
      impact of tumor volume and delivered dose on failure-free interval (FFI) and
      overall survival (OS) were also studied. METHODS AND MATERIALS: A Phase I/II
      trial was performed including inoperable NSCLC patients. According to the
      relative mean lung dose (rMLD), five risk groups with different starting doses
      were defined: Group 1, rMLD 0.0 to 0.12; Group 2, rMLD 0.12 to 0.18; Group 3,
      rMLD 0.18 to 0.24; Group 4, rMLD 0.24 to 0.31; and Group 5, rMLD 0.31 to 0.40.
      Patients underwent irradiation with 2.25 Gy per fraction and a fixed overall
      treatment time of 6 weeks. The dose was escalated with 6.75 Gy after 6 months
      follow-up without dose-limiting toxicity. If more than 30 fractions were
      prescribed, twice-daily irradiation was performed with at least a 6-h interval.
      RESULTS: A total of 88 patients were included. Tumor Stage I or II was found in
      53%, IIIA in 31%, and IIIB in 17%. The MTD was not achieved in risk Group 1
      (reached dose, 94.5 Gy). For risk Groups 2 and 3 the MTD was 81 Gy. The 74.3-Gy
      dose was determined to be safe for Group 4 and the 60.8-Gy dose for Group 5. In 2
      patients (5%) an isolated nodal relapse occurred. Based on multivariable
      analysis, higher doses significantly increased the FFI (p = 0.02) for the total
      group. The OS was increased in the lower risk groups (p = 0.05) but not in the
      higher risk groups (p = 0.4). CONCLUSION: Dose escalation is safe up to 94.5 Gy
      in 42 fractions in 6 weeks in patients with an MLD 13.6 Gy or less. Higher doses
      are associated with a better FFI and OS for smaller tumor volumes. Involved-field
      irradiation results in a low percentage of isolated nodal relapses.

PMID- 16904519
TI  - Preliminary results of a randomized study (NPC-9902 Trial) on therapeutic gain by
      concurrent chemotherapy and/or accelerated fractionation for locally advanced
      nasopharyngeal carcinoma.
AB  - PURPOSE: To compare the benefit achieved by concurrent chemoradiotherapy (CRT)
      and/or accelerated fractionation (AF) vs. radiotherapy (RT) alone with
      conventional fractionation (CF) for patients with T3-4N0-1M0 nasopharyngeal
      carcinoma (NPC). METHODS AND MATERIALS: All patients were irradiated with the
      same RT technique to > or =66 Gy at 2 Gy per fraction, conventional five
      fractions/week in the CF and CF+C (chemotherapy) arms, and accelerated six
      fractions/week in the AF and AF+C arms. The CF+C and AF+C patients were given the
      Intergroup 0099 regimen (concurrent cisplatin plus adjuvant cisplatin and 5
      fluorouracil). RESULTS: Between 1999 and April 2004, 189 patients were randomly
      assigned; the trial was terminated early because of slow accrual. The median
      follow-up was 2.9 years. When compared with the CF arm, significant improvement
      in failure-free survival (FFS) was achieved by the AF+C arm (94% vs. 70% at 3
      years, p = 0.008), but both the AF arm and the CF+C arm were insignificant (p >
      or = 0.38). Multivariate analyses showed that CRT was a significant factor:
      hazard ratio (HR) = 0.52 (0.28-0.97), AF per se was insignificant: HR = 0.68
      (0.37-1.25); the interaction of CRT by AF was strongly significant (p = 0.006).
      Both CRT arms had significant increase in acute toxicities (p < 0.005), and the
      AF+C arm also incurred borderline increase in late toxicities (34% vs. 14% at 3
      years, p = 0.05). CONCLUSIONS: Preliminary results suggest that concurrent
      chemoradiotherapy with accelerated fractionation could significantly improve
      tumor control when compared with conventional RT alone; further confirmation of
      therapeutic ratio is warranted.

PMID- 16904520
TI  - Adenoid cystic carcinoma of the head and neck treated by surgery with or without
      postoperative radiation therapy: prognostic features of recurrence.
AB  - PURPOSE: This study sought to review a single-institution experience with the
      management of adenoid cystic carcinoma of the head and neck. METHODS AND
      MATERIALS: Between 1960 and 2004, 140 patients with adenoid cystic carcinoma of
      the head and neck were treated with definitive surgery. Ninety patients (64%)
      received postoperative radiation to a median dose of 64 Gy (range, 54-71 Gy).
      Distribution of T stage was: 26% T1, 28% T2, 20% T3, and 26% T4. Seventy-eight
      patients (56%) had microscopically positive margins. Median follow-up was 66
      months (range, 7-267 months). RESULTS: The 5- and 10-year rate estimates of local
      control were 88% and 77%, respectively. A Cox proportional hazards model
      identified T4 disease (p = 0.0001), perineural invasion (p = 0.008), omission of
      postoperative radiation (p = 0.007), and major nerve involvement (p = 0.02) as
      independent predictors of local recurrence. Radiation dose lower than 60 Gy (p =
      0.0004), T4 disease (p = 0.005), and major nerve involvement (p = 0.02) were
      predictors of local recurrence among those treated with surgery and postoperative
      radiation. The 10-year overall survival and distant metastasis-free survival were
      64% and 66%, respectively. CONCLUSION: Combined-modality therapy with surgery
      followed by radiation to doses in excess of 60 Gy should be considered the
      standard of care for adenoid cystic carcinoma of the head and neck.

PMID- 16904521
TI  - Twenty years' experience in the treatment of acoustic neuromas with fractionated
      radiotherapy: a review of 45 cases.
AB  - PURPOSE: To evaluate very long-term results of fractionated radiotherapy (FRT) of
      acoustic neuromas (AN). METHODS AND MATERIALS: From January 1986 to January 2004,
      FRT was performed in 45 consecutive patients (46 AN). Indications were as
      follows: poor general condition contraindicating surgery, hearing preservation in
      bilateral neuromas, partial resection, nonsurgical recurrence. A 3-field to 5
      field technique with static beams was used. A mean total dose of 51 Gy was given
      (1.80 Gy/fraction). The median tumor diameter was 31 mm (range, 11-55 mm). The
      median follow-up from FRT was 80 months (range, 4-227 months). RESULTS: The
      particularity of our series consists of a very long-term follow-up of FRT given
      to selected patients. Nineteen patients died, two with progressive disease, and
      17 from non-AN causes. A serviceable level of hearing was preserved in 7/9
      hearing patients. No patient had facial or trigeminal neuropathy. Tumor shrinkage
      was observed in 27 (59%) and stable disease in 16 (35%). Tumor progression
      occurred in three patients, 12 to 15 months after FRT. Two additional tumors
      recurred after shrinkage 20 and 216 months after treatment and were operated on.
      Actuarial local tumor control rates at 5 and 15 years were 86%. For the patient
      who had a tumor recurrence at 216 months, histologic examination documented
      transformation to a low-grade malignant peripheral nerve sheath tumor.
      CONCLUSION: Very long-term efficacy of FRT is well documented in this series.
      However, our results suggest that malignant transformation can occur many years
      after FRT so we advocate caution when using this treatment for young patients.

PMID- 16904522
TI  - Combined modality therapy for HIV-infected patients with squamous cell carcinoma
      of the anus: outcomes and toxicities.
AB  - PURPOSE: We report toxicity and survival data of human immunodeficiency virus
      (HIV)-infected men with anal carcinoma treated with combined modality therapy
      (CMT) of radiotherapy and concurrent chemotherapy. METHODS AND MATERIALS: A
      retrospective review was performed on the records of 17 HIV-positive patients
      with anal squamous cell carcinoma treated with CMT at our institution between
      1991 and 2004. Radiotherapy consisted of 30.6 to 45 Gy to the pelvis, total dose
      of 50.4 to 59.4 Gy to initial gross disease, at 1.8 Gy/fraction. Chemotherapy
      consisted of 5-fluorouracil and either mitomycin C or cisplatin. The mean follow
      up was 25.6 months (median, 15.6 months; range, 4.6-106 months). RESULTS:
      Significant acute skin and hematologic toxicity developed in 8 of 17 and 9 of 17
      patients, respectively. One patient died 12 days after treatment of progressive
      disease and sepsis. Significant late toxic sequelae developed in 3 patients: 1
      anorectal ulcer, 2 dermatologic (perianal ulceration, hemorrhagic perineal sores
      and suspected fissure). Fourteen of 15 patients with Stage I-III disease had a
      complete response; 2 complete responders subsequently had a relapse in the
      anorectum. For all patients, actuarial 18-month survival was 67%. For patients
      with Stage I-III disease, survival at last follow-up by low CD4 count (<200) vs.
      high count (>200) was 4 of 7 vs. 7 of 8, respectively; significant acute
      toxicities developed in 4 of 8 vs. 6 of 9, respectively. CONCLUSION: For HIV
      patients with anal carcinoma, CMT yields reasonable local control with
      significant acute complications. Survival is lower than in the general
      population, attributable more to the underlying infection than to the malignancy.

PMID- 16904523
TI  - Clinical dose-volume histogram analysis in predicting radiation pneumonitis in
      Hodgkin's lymphoma.
AB  - PURPOSE: To quantify the incidence of radiation pneumonitis (RP) in a modern
      Hodgkin's lymphoma (HL) cohort, and to identify any clinically relevant
      parameters that may influence the risk of RP. METHODS AND MATERIALS: Between
      January 2003 and February 2005, 64 consecutive HL patients aged 18 years or older
      receiving radical mediastinal radiation therapy (RT) were retrospectively
      reviewed. Symptomatic cases of radiation pneumonitis were identified. Dose-volume
      histogram parameters, including V(13), V(20), V(30), and mean lung dose (MLD),
      were quantified. RESULTS: At a median follow-up of 2.1 years, the actuarial
      survival for all patients was 91% at 3 years. There were 2 (2/64) cases of
      Radiation Therapy Oncology Group (RTOG) Grade 2 RP (incidence 3.1%). Both index
      cases with corresponding V(20) values of 47.0% and 40.7% were located in the
      upper quartile (2/16 cases), defined by a V(20) value of > or =36%, an incidence
      of 12.5% (p = 0.03). Similarly for total MLD, both index cases with values of
      17.6 Gy and 16.4 Gy, respectively, were located in the upper quartile defined by
      MLD > or =14.2 Gy, an incidence of 11.8% (2/17 cases, p = 0.02). CONCLUSIONS:
      Despite relatively high V(20) values in this study of HL patients, the incidence
      of RP was only 3%, lower compared with the lung cancer literature. We suggest the
      following clinically relevant parameters be considered in treatment plan
      assessment: a V(20) greater than 36% and an MLD greater than 14 Gy, over and
      above which the risk of RTOG Grade 2 or greater RP would be considered clinically
      significant.

PMID- 16904524
TI  - Effectiveness of a clinical intervention in improving pain control in outpatients
      with cancer treated by radiation therapy.
AB  - PURPOSE: To determine the effectiveness of a multicomponent clinical intervention
      to reduce pain in outpatients with cancer. METHODS AND MATERIALS: Sixty-four
      patients were randomly assigned to receive either a clinical intervention
      including an information session, the use of a pain diary, and the possibility to
      contact a physician to adjust the pain medication, or the usual treatment of pain
      by the staff radiation oncologist. All patients reported their average and worst
      pain levels at baseline and 2 and 3 weeks after the start of the intervention.
      RESULTS: The study groups were similar with respect to their baseline
      characteristics and pain levels at randomization. After 3 weeks, the average and
      worst pain experienced by patients randomized to the clinical intervention group
      was significantly inferior to the average pain experienced by patients in the
      control group (2.9/10 vs. 4.4/10 and 4.2/10 vs. 5.5/10, respectively). Results
      showed that the experimental group patients decreased their pain levels more than
      the control group patients did over time. CONCLUSION: An intervention including
      patient education, a pain diary, and defining a procedure for therapeutic
      adjustments can be effective to improve pain relief in outpatients with cancer.

PMID- 16904525
TI  - A protective role for keratinocyte growth factor in a murine model of
      chemotherapy and radiotherapy-induced mucositis.
AB  - PURPOSE: To evaluate the activity of palifermin (rHuKGF) in a murine model of
      mucosal damage induced by a radiotherapy/chemotherapy (RT/CT) regimen mimicking
      treatment protocols used in head-and-neck cancer patients. METHODS AND MATERIALS:
      A model of mucosal damage induced by RT/CT was established by injecting female
      BDF1 mice with cisplatin (10 mg/kg) on Day 1; 5-fluorouracil (40 mg/kg/day) on
      Days 1-4, and irradiation (5 Gy/day) to the head and neck on Days 1-5. Palifermin
      was administered subcutaneously on Days -2 to 0 (5 mg/kg/day) and on Day 5 (5
      mg/kg). Evaluations included body weight, organ weight, keratinocyte growth
      factor receptor expression, epithelial thickness, and cellular proliferation.
      RESULTS: Initiation of the radiochemotherapeutic regimen resulted in a reduction
      in body weight in control animals. Palifermin administration suppressed weight
      loss and resulted in increased organ weight (salivary glands and small
      intestine), epithelial thickness (esophagus and tongue), and cellular
      proliferation (tongue and salivary glands). CONCLUSIONS: Administration of
      palifermin before RT/CT promotes cell proliferation and increases in epithelial
      thickness in the oral mucosa, salivary glands, and digestive tract. Palifermin
      administration before and after RT/CT mitigates weight loss and a trophic effect
      on the intestinal mucosa and salivary glands, suggesting that palifermin use
      should be investigated further in the RT/CT settings, in which intestinal
      mucositis and salivary gland dysfunction are predominant side effects of
      cytotoxic therapy.

PMID- 16904526
TI  - Response of intracerebral human glioblastoma xenografts to multifraction
      radiation exposures.
AB  - PURPOSE: We investigated the effects of fractionated radiation treatments on the
      life spans of athymic rats bearing intracerebral brain tumors. METHODS AND
      MATERIALS: U-251 MG or U-87 MG human glioblastoma cells were implanted into the
      brains of athymic rats, and the resulting tumors were irradiated once daily with
      various doses of ionizing radiation for 5 consecutive days or for 10 days with a
      2-day break after Day 5. RESULTS: Five daily doses of 1 and 1.5 Gy, and 10 doses
      of 0.75 and 1 Gy, cured some U-251 MG tumors. However, five daily doses of 0.5 Gy
      increased the survival time of animals bearing U-251 MG tumors 5 days without
      curing any animals of their tumors. Ten doses of 0.3 Gy given over 2 weeks
      extended the lifespan of the host animals 9 days without curing any animals. For
      U-87 MG tumors, 5 daily doses of 3 Gy produced an increased lifespan of 8 days
      without curing any animals, and 10 doses of 1 Gy prolonged lifespan 5.5 days
      without curing any animals. The differences in extension of life span between the
      5- and 10-fraction protocols were minor for either tumor type. CONCLUSION: The
      finding that the U-251 MG tumors are more sensitive than U-87 MG tumors, despite
      the fact that U-251 MG tumors contain many more hypoxic cells than U-87 MG
      tumors, suggests the intrinsic cellular radiosensitivities of these cell lines
      are more important than hypoxia in determining their in vivo radiosensitivities.

PMID- 16904527
TI  - Limitations of the planning organ at risk volume (PRV) concept.
AB  - PURPOSE: Previously, we determined a planning target volume (PTV) margin recipe
      for geometrical errors in radiotherapy equal to M(T) = 2 Sigma + 0.7 sigma, with
      Sigma and sigma standard deviations describing systematic and random errors,
      respectively. In this paper, we investigated margins for organs at risk (OAR),
      yielding the so-called planning organ at risk volume (PRV). METHODS AND
      MATERIALS: For critical organs with a maximum dose (D(max)) constraint, we
      calculated margins such that D(max) in the PRV is equal to the motion averaged
      D(max) in the (moving) clinical target volume (CTV). We studied margins for the
      spinal cord in 10 head-and-neck cases and 10 lung cases, each with two different
      clinical plans. For critical organs with a dose-volume constraint, we also
      investigated whether a margin recipe was feasible. RESULTS: For the 20 spinal
      cords considered, the average margin recipe found was: M(R) = 1.6 Sigma + 0.2
      sigma with variations for systematic and random errors of 1.2 Sigma to 1.8 Sigma
      and -0.2 sigma to 0.6 sigma, respectively. The variations were due to differences
      in shape and position of the dose distributions with respect to the cords. The
      recipe also depended significantly on the volume definition of D(max). For
      critical organs with a dose-volume constraint, the PRV concept appears even less
      useful because a margin around, e.g., the rectum changes the volume in such a
      manner that dose-volume constraints stop making sense. CONCLUSION: The concept of
      PRV for planning of radiotherapy is of limited use. Therefore, alternative ways
      should be developed to include geometric uncertainties of OARs in radiotherapy
      planning.

PMID- 16904528
TI  - Design of 4D treatment planning target volumes.
AB  - PURPOSE: When using non-patient-specific treatment planning margins, respiratory
      motion may lead to geometric miss of the target while unnecessarily irradiating
      normal tissue. Imaging different respiratory states of a patient allows patient
      specific target design. We used four-dimensional computed tomography (4DCT) to
      characterize tumor motion and create treatment volumes in 10 patients with lung
      cancer. These were compared with standard treatment volumes. METHODS AND
      MATERIALS: Four-dimensional CT and free breathing helical CT data of 10 patients
      were acquired. Gross target volumes (GTV) were delineated on the helical scan as
      well as on each phase of the 4D data. Composite GTVs were defined on 4DCT.
      Planning target volumes (PTV) including clinical target volume, internal margin
      (IM), and setup margin were generated. 4DPTVs with different IMs and standard
      PTVs were compared by computing centroid positions, volumes, volumetric overlap,
      and bounding boxes. RESULTS: Four-dimensional PTVs and conventional PTVs differed
      in volume and centroid positions. Overlap between 4DPTVs generated from two
      extreme tumor positions only compared with 10 respiratory phases was 93.7%.
      Comparing PTVs with margins of 15 mm (IM 5 mm) on composite 4D target volumes to
      PTVs with 20 mm (IM 10 mm) on helical CT data resulted in a decrease in target
      volume sizes by 23% on average. CONCLUSION: With patient-specific
      characterization of tumor motion, it should be possible to decrease internal
      margins. Patient-specific treatment volumes can be generated using extreme tumor
      positions on 4DCT. To date, more than 150 patients have been treated using 4D
      target design.

PMID- 16904529
TI  - Geometric factors influencing dosimetric sparing of the parotid glands using
      IMRT.
AB  - PURPOSE/OBJECTIVE: To determine the relationship between the parotid volume,
      parotid-planning target volume (PTV) overlap, and dosimetric sparing of the
      parotid with intensity-modulated radiation therapy (IMRT). METHODS AND MATERIALS:
      Parotid data were collected retrospectively for 51 patients treated with
      simultaneous boost IMRT. Unresectable patients received 54 or 59.4 Gy to
      subclinical disease, 70 Gy to gross disease. Patients treated postoperatively
      received 54, 60, and 66 Gy to low-risk, high-risk, and tumor bed regions. Volume
      and mean dose of each gland and gland segments outside of and overlapping the PTV
      were collected. Proximity of each gland to each PTV was recorded. RESULTS:
      Dosimetric sparing (mean dose <or =26.5 Gy) was achieved in 66 of 71 glands with
      < or =21% parotid-PTV overlap and 8 of 23 glands with >21% overlap (p = <0.0001).
      Among spared glands, the median mean dose in the overlap region was 55.0 Gy in
      glands with < or =21% overlap, but only 45.4 Gy when overlap >21%. Median mean
      dose was 25.9 Gy to glands overlapping PTV(54) or PTV(59) alone and 30.0 Gy to
      those abutting PTV(70) (p < 0.001). Although proximity to PTV(70) was associated
      with higher parotid dose, satisfactory sparing was achieved in 24 of 43
      ipsilateral glands. CONCLUSIONS: Dosimetric sparing of the parotid is feasible
      when the parotid-PTV overlap is less than approximately 20%. With more overlap,
      sparing may result in low doses within the overlap region, possibly leading to
      inadequate PTV coverage. Gland proximity to the high-dose PTV is associated with
      higher mean dose but does not always preclude dosimetric sparing.

PMID- 16904530
TI  - Do metallic ports in tissue expanders affect postmastectomy radiation delivery?
AB  - PURPOSE: Postmastectomy radiation therapy (PMRT) is often delivered to patients
      with permanent breast implants. On occasion, patients are irradiated with a
      tissue expander (TE) in place before their permanent implant exchange. Because of
      concern of potential under-dosing in these patients, we examined the dosimetric
      effects of the Magna-Site (Santa Barbara, CA) metallic port that is present in
      certain TEs. METHODS AND MATERIALS: We performed ex vivo film dosimetry with
      single 6-MV and 15-MV photon beams on a water phantom containing a Magna-Site
      disc in two orientations. Additionally, using in vivo films, we measured the exit
      dose from 1 patient's TE-reconstructed breast during chest wall treatment with 15
      MV tangent beams. Finally, we placed thermoluminescent dosimeters (TLDs) on 6
      patients with TEs who received PMRT delivered with 15-MV tangent beams. RESULTS:
      Phantom film dosimetry revealed decreased transmission in the region of the Magna
      Site, particularly with the magnet in the parallel orientation (at 22 mm: 78%
      transmission with 6 MV, 84% transmission with 15 MV). The transmission measured
      by in vivo films during single beam treatment concurred with ex vivo results. TLD
      data showed acceptable variation in median dose to the skin (86-101% prescription
      dose). CONCLUSION: Because of potential dosimetric effects of the Magna-Site, it
      is preferable to treat PMRT patients with permanent implants. However, it is not
      unreasonable to treat with a TE because the volume of tissue affected by
      attenuation from the Magna-Site is small. In this scenario, we recommend using 15
      MV photons with compensating bolus.

PMID- 16904531
TI  - Concurrent administration of adjuvant chemotherapy and radiotherapy after breast
      conserving surgery: in regards to Toledano et al. (Int J Radiat Oncol Biol Phys
      2006;65:324-332).

PMID- 16904534
TI  - The effects of diet on inflammation: emphasis on the metabolic syndrome.
AB  - Reducing the incidence of coronary heart disease with diet is possible. The main
      dietary strategies include adequate omega-3 fatty acids intake, reduction of
      saturated and trans-fats, and consumption of a diet high in fruits, vegetables,
      nuts, and whole grains and low in refined grains. Each of these strategies may be
      associated with lower generation of inflammation. This review examines the
      epidemiologic and clinical evidence concerning diet and inflammation. Dietary
      patterns high in refined starches, sugar, and saturated and trans-fatty acids,
      poor in natural antioxidants and fiber from fruits, vegetables, and whole grains,
      and poor in omega-3 fatty acids may cause an activation of the innate immune
      system, most likely by an excessive production of proinflammatory cytokines
      associated with a reduced production of anti-inflammatory cytokines. The whole
      diet approach seems particularly promising to reduce the inflammation associated
      with the metabolic syndrome. The choice of healthy sources of carbohydrate, fat,
      and protein, associated with regular physical activity and avoidance of smoking,
      is critical to fighting the war against chronic disease. Western dietary patterns
      warm up inflammation, while prudent dietary patterns cool it down.

PMID- 16904535
TI  - Young Adult Myocardial Infarction and Ischemic Stroke: the role of paradoxical
      embolism and thrombophilia (The YAMIS Study).
AB  - OBJECTIVES: We aimed to investigate the frequency of venous-to-arterial
      circulation shunts (v-aCS), usually caused by patent foramen ovale (PFO), and
      thrombophilia in young adults suffering myocardial infarction (MI) and ischemic
      stroke (IS) and matched healthy control subjects. BACKGROUND: The cause of MI and
      IS in young adults is often uncertain, and paradoxical embolism might be more
      frequent than previously thought. METHODS: Young adults (ages 16 to 39 years)
      surviving MI (n = 101) and IS (n = 101) between 1993 and 1998 were matched by age
      and gender to 202 control subjects from the same general practitioner practices.
      The v-aCS were detected by transcranial Doppler after intravenous microbubble
      ultrasound contrast; "significant" v-aCS (> or =15 microbubble emboli) correlated
      with PFO on transesophageal echocardiography. A "major" v-aCS was >50
      microbubbles spontaneously or >10 microbubbles spontaneously with >80 after
      provocation. Venous blood was taken for a thrombophilia screen. RESULTS:
      Myocardial infarction, more frequent in men, was associated with the usual
      cardiovascular risk factors. More women suffered IS, which was associated only
      with migraine and hypertension. Neither "significant" nor "major" v-aCS were
      associated with MI. "Major" v-aCS was found in 24 (25%) IS cases compared with 12
      (12%) control subjects (odds ratio 2.80, 95% confidence interval 1.21 to 6.84; p
      = 0.016). Thrombophilia was not significantly associated with either MI or IS.
      CONCLUSIONS: Only "major" v-aCS were associated with stroke in young adults.
      Closure of smaller v-aCS might not be justified.

PMID- 16904536
TI  - A meta-analysis of the renal safety of isosmolar iodixanol compared with low
      osmolar contrast media.
AB  - OBJECTIVES: We sought to compare the nephrotoxicity of isosmolar contrast medium
      (IOCM) iodixanol with low-osmolar contrast media (LOCM) and to identify
      predictors of contrast-induced nephropathy (CIN). BACKGROUND: Contrast-induced
      nephropathy is a serious complication of diagnostic and interventional
      procedures. METHODS: Pooled individual patient data (n = 2,727) from 16 double
      blind, randomized, controlled trials in which patients received either intra
      arterial IOCM iodixanol (n = 1,382) or LOCM (n = 1,345) were included. Patients
      were stratified according to chronic kidney disease (CKD), diabetes mellitus
      (DM), or both. Outcome measures were the maximum increase in serum creatinine
      (Cr) over baseline and the incidence of postprocedural CIN. RESULTS: The maximum
      Cr increase within 3 days after contrast medium (CM) administration was
      significantly smaller in the iodixanol group compared with the LOCM group (0.06
      mg/dl vs. 0.10 mg/dl, p < 0.001), particularly in patients with CKD (0.07 mg/dl
      vs. 0.16 mg/dl, p = 0.004) and CKD + DM (0.10 mg/dl vs. 0.33 mg/dl, p = 0.003).
      Contrast-induced nephropathy, defined as an increase in Cr > or =0.50 mg/dl
      within 3 days after CM administration, occurred less frequently in the iodixanol
      group than in the LOCM group in all patients (1.4% vs. 3.5%, p < 0.001), in CKD
      patients (2.8% vs. 8.4%, p = 0.001), and in CKD + DM patients (3.5% vs. 15.5%, p
      = 0.003). Independent predictors of CIN included CKD, CKD + DM, and use of LOCM.
      CONCLUSIONS: This meta-analysis of pooled data from 2,727 patients indicates that
      use of the IOCM iodixanol is associated with smaller rises in Cr and lower rates
      of CIN than LOCM, especially in patients with CKD or CKD + DM.

PMID- 16904537
TI  - Caffeine prevents protection in two human models of ischemic preconditioning.
AB  - OBJECTIVES: We studied whether caffeine impairs protection by ischemic
      preconditioning (IP) in humans. BACKGROUND: Ischemic preconditioning is
      critically dependent on adenosine receptor stimulation. We hypothesize that the
      adenosine receptor antagonist caffeine blocks the protective effect of IP.
      METHODS: In vivo ischemia-reperfusion injury was assessed in the thenar muscle by
      99mTc-annexin A5 scintigraphy. Forty-two healthy volunteers performed forearm
      ischemic exercise. In 24 subjects, this was preceded by a stimulus for IP. In a
      randomized double-blinded design, the subjects received caffeine (4 mg/kg) or
      saline intravenously before the experiment. At reperfusion, 99mTc-annexin A5 was
      administered intravenously. Targeting of annexin was quantified by region-of
      interest analysis, and expressed as percentage difference between experimental
      and contralateral hand. In vitro, we assessed recovery of contractile function of
      human atrial trabeculae, harvested during heart surgery, as functional end point
      of ischemia-reperfusion injury. Field-stimulated contraction was quantified at
      baseline and after simulated ischemia-reperfusion, in a paired approach with and
      without 5 min of IP, in the presence (n=13) or absence (n = 17) of caffeine (10
      mg/l). RESULTS: Ischemic preconditioning reduced annexin targeting in the absence
      of caffeine (from 13 +/- 3% to 7 +/- 1% at 1 h, and from 19 +/- 2% to 9 +/- 3% at
      4 h after reperfusion, p = 0.006), but not after caffeine administration
      (targeting 11 +/- 2% and 16 +/- 3% at 1 and 4 h). In vitro, IP improved post
      ischemic functional recovery in the control group, but not in the caffeine group
      (8 +/- 3% vs. -8 +/- 5%, p=0.003). CONCLUSIONS: Caffeine abolishes IP in 2 human
      models at a dose equivalent to the drinking of 2 to 4 cups of coffee. (The Effect
      of Caffeine on Ischemic Preconditioning;
      http://clinicaltrials.gov/ct/show/NCT00184912?order=1; NCT00184912).

PMID- 16904538
TI  - Cholesterol and glucose metabolism and recurrent cardiovascular events among the
      elderly: a prospective study.
AB  - OBJECTIVES: The aim of this research was to evaluate the prognostic value of
      cholesterol absorption assessed with the serum cholestanol-to-cholesterol
      concentration ratio (lower level reflects decreased cholesterol absorption) among
      elderly cardiovascular patients (DEBATE [Drugs and Evidence-Based Medicine in the
      Elderly] study). BACKGROUND: The components of the metabolic syndrome have been
      unexpectedly associated with better prognosis among elderly cardiovascular
      patients. On the other hand, a metabolic syndrome-type state is characterized by
      high synthesis and decreased absorption of cholesterol. METHODS: This was a
      prospective cohort study of home-dwelling individuals age 75 years and older with
      cardiovascular diseases (247 women, 129 men) recruited from the community. Main
      outcome measure was multivariate-adjusted time to 3.4-year mortality and
      recurrent major cardiovascular events. RESULTS: Serum total and low-density
      lipoprotein cholesterol levels did not predict outcome. Instead, the mortality
      risk (64 deaths) increased with increasing levels of cholestanol-to-cholesterol
      ratio. Patients in the 2nd, 3rd, and 4th quartiles had a relative hazard ratio
      (HR) for death of 2.54 (95% confidence interval [CI] 1.05 to 6.12), 2.48 (95% CI
      1.03 to 6.00), and 3.53 (95% CI 1.52 to 8.19) compared with the lowest quartile,
      even though 50% of individuals in the lowest cholestanol quartile had metabolic
      syndrome or diabetes. In multivariate models, the lowest cholestanol ratio
      quartile was independently associated with lower mortality (relative HR, 0.37,
      95% CI 0.17 to 0.81), and with fewer major cardiovascular events (115 events,
      relative HR, 0.59, 95% CI 0.35 to 0.98). CONCLUSIONS: Low cholesterol absorption
      was associated with fewer recurrent cardiovascular events, and with better
      survival in elderly patients despite frequent abnormalities of glucose
      metabolism.

PMID- 16904539
TI  - Consumption of saturated fat impairs the anti-inflammatory properties of high
      density lipoproteins and endothelial function.
AB  - OBJECTIVES: The purpose of this study was to investigate the influence of dietary
      fatty acids on the anti-inflammatory properties of high-density lipoproteins
      (HDL) and vascular function. BACKGROUND: The effect of dietary fatty acids on
      atherogenesis remains uncertain. METHODS: Fourteen adults consumed an isocaloric
      meal containing either a polyunsaturated or a saturated fat on 2 occasions. The
      effects of post-prandial HDL on endothelial cell expression of intercellular
      adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were
      determined. Flow-mediated dilation (FMD) and microvascular reactivity were
      assessed before and 3 and 6 h after the meal. RESULTS: Plasma triglycerides,
      insulin, and nonesterified fatty acids rose after the meals. The HDL collected 6
      h after the saturated meal were less effective than HDL isolated from fasting
      plasma in terms of their ability to inhibit expression of ICAM-1 and VCAM-1,
      whereas HDL collected 6 h after the polyunsaturated meal had an inhibitory
      activity that was greater than that of HDL collected from fasting plasma (p <
      0.004 and p = 0.01 for comparison of effect of meals on ICAM-1 and VCAM-1,
      respectively). Post-hyperemic microvascular flow significantly increased at 3 h
      after the polyunsaturated meal by 45 +/- 14% and by 21 +/- 11% after the
      saturated meal. The FMD decreased 3 h after the saturated meal by 2.2 +/- 0.9%
      (p< 0.05 compared with baseline) and by 0.9 +/- 1% after the polyunsaturated
      meal. CONCLUSIONS: Consumption of a saturated fat reduces the anti-inflammatory
      potential of HDL and impairs arterial endothelial function. In contrast, the anti
      inflammatory activity of HDL improves after consumption of polyunsaturated fat.
      These findings highlight novel mechanisms by which different dietary fatty acids
      may influence key atherogenic processes.

PMID- 16904540
TI  - Quality of life and exercise performance in patients in sinus rhythm versus
      persistent atrial fibrillation: a Veterans Affairs Cooperative Studies Program
      Substudy.
AB  - OBJECTIVES: The purpose of this study was to determine quality of life (QOL) and
      exercise performance (EP) in patients with persistent atrial fibrillation (AF)
      converted to sinus rhythm (SR) compared with those remaining in or reverting to
      AF. BACKGROUND: Restoration of SR in patients with AF improving QOL and EP
      remains controversial. METHODS: Patients with persistent AF were randomized
      double-blind to amiodarone, sotalol, or placebo. Those not achieving SR at day 28
      were cardioverted and classified into SR or AF groups at 8 weeks (n = 624) and 1
      year (n = 556). The QOL (SF-36), symptom checklist (SCL), specific activity scale
      (SAS), AF severity scale (AFSS), and EP were assessed. RESULTS: Favorable changes
      were seen in SR patients at 8 weeks in physical functioning (p < 0.001), physical
      role limitations (p = 0.03), general health (p = 0.002), and vitality (p <
      0.001), and at 1 year in general health (p = 0.007) and social functioning (p =
      0.02). Changes in the scores for SCL severity (p = 0.01), functional capacity (p
      = 0.003), and AFSS symptom burden (p < 0.001) at 8 weeks and in SCL severity (p <
      0.01) and AF symptom burden (p < 0.001) at 1 year showed significant improvements
      in SR versus AF. Symptomatic patients were more likely to have improvement. The
      EP in SR versus AF was greater from baseline to 8 weeks (p = 0.01) and to 1 year
      (p = 0.02). The EP correlated with physical functioning and functional capacity
      except in the AF group at 1 year. CONCLUSIONS: In patients with persistent AF,
      restoration and maintenance of SR was associated with improvements in QOL
      measures and EP. There was a strong correlation between QOL measures and EP.

PMID- 16904541
TI  - Atrial fibrillation or sinus rhythm? Controversy and contradiction in quality of
      life outcomes.

PMID- 16904542
TI  - Four-year efficacy of cardiac resynchronization therapy on exercise tolerance and
      disease progression: the importance of performing atrioventricular junction
      ablation in patients with atrial fibrillation.
AB  - OBJECTIVES: The goal of this study was to investigate the effects of cardiac
      resynchronization therapy (CRT) in heart failure patients with permanent atrial
      fibrillation (AF) and the role of atrioventricular junction (AVJ) ablation.
      BACKGROUND: Cardiac resynchronization therapy has been proven effective in heart
      failure patients with sinus rhythm (SR). However, little is known about the
      effects of CRT in heart failure patients with permanent AF. METHODS: Efficacy of
      CRT on ventricular function, exercise performance, and reversal of maladaptive
      remodeling process was prospectively compared in 48 patients with permanent AF in
      whom ventricular rate was controlled by drugs, thus resulting in apparently
      adequate delivery of biventricular pacing (>85% of pacing time), and in 114
      permanent AF patients, who had undergone AVJ ablation (100% of resynchronization
      therapy delivery). The clinical and echocardiographic long-term outcomes of both
      groups were compared with those of 511 SR patients treated with CRT. RESULTS:
      Both SR and AF groups showed significant and sustained improvements of all
      assessed parameters (model p < 0.001 for all parameters). However, within the AF
      group, only patients who underwent ablation showed a significant increase of
      ejection fraction (p < 0.001), reverse remodeling effect (p < 0.001), and
      improved exercise tolerance (p < 0.001); no improvements were observed in AF
      patients who did not undergo ablation. CONCLUSIONS: Heart failure patients with
      ventricular conduction disturbance and permanent AF treated with CRT showed large
      and sustained long-term (up to 4 year) improvements of left ventricular function
      and functional capacity, similar to patients in SR, only if AVJ ablation was
      performed.

PMID- 16904543
TI  - Desperately seeking a randomized clinical trial of resynchronization therapy for
      patients with heart failure and atrial fibrillation.

PMID- 16904544
TI  - Effects of beta-blocker therapy on ventricular repolarization documented by 24-h
      electrocardiography in patients with type 1 long-QT syndrome.
AB  - OBJECTIVES: We tested the hypothesis that in long-QT syndrome (LQT) type 1
      (LQT1), beta-blocker therapy may decrease both the diurnal maximal T-wave peak to
      T-wave end interval (TPE) and the maximal ratio between late and early T-wave
      peak amplitude (T2/T1 ratio), which are electrocardiographic counterparts of
      transmural dispersion of repolarization (TDR) and early afterdepolarizations
      (EA), respectively. BACKGROUND: Ventricular repolarization duration and increased
      TDR and EAs are the three electrophysiological components generating the high
      risk of ventricular arrhythmias and sudden death in the inherited LQT. In the
      most prevalent LQT1 form of LQT, treatment with beta-blockers reduces serious
      arrhythmia events dramatically without a known influence on QT interval duration.
      In experimental LQT1 models, beta-blockers decrease TDR and prevent EAs. METHODS:
      We reviewed 24-h electrocardiographic recordings obtained before and during the
      treatment with beta-blockers from 24 genotyped LQT1 patients to record maximal
      TPE intervals and T2/T1 ratios as well as maximal and rate-adapted QT intervals
      using a computer-assisted program. RESULTS: Treatment with beta-blockers
      decreased the maximal diurnal T2/T1 amplitude ratio from 3.0+/- 1.0 to 2.2 +/-
      0.6 (p = 0.002). Beta-blockers also decreased both maximal TPE intervals and
      abrupt maximal QT intervals at heart rates higher than 85 beats/min, whereas QT
      intervals measured at steady-state conditions remained unchanged. CONCLUSIONS:
      Prevention of abrupt increases of electrocardiographic TDR, EA, and ventricular
      repolarization duration at elevated heart rates may explain the favorable
      clinical effects of beta-blockers in LQT1.

PMID- 16904545
TI  - The potential of myocardial perfusion scintigraphy for risk stratification of
      asymptomatic patients with type 2 diabetes.
AB  - Patients with diabetes, in particular patients with type 2 diabetes, are at a 2-
      to 4-fold higher risk of cardiovascular mortality compared with their nondiabetic
      peers. Patients with diabetes are also more likely to have silent ischemia and
      less likely to survive a myocardial infarction than nondiabetic patients. Recent
      studies with electron beam computed tomography (EBCT) have shown that subclinical
      atherosclerosis is common in patients with diabetes, and studies with myocardial
      perfusion scintigraphy (with single-photon emission computed tomography) or
      stress echocardiography have demonstrated that between 25% and 50% of
      asymptomatic diabetic patients have ischemia during exercise or pharmacological
      stress and that a substantial proportion of these patients go on to develop major
      cardiovascular events within several years. Clearly, asymptomatic diabetic
      patients include a subset of individuals at high risk of cardiovascular disease
      who would benefit from improved risk stratification beyond that possible with
      risk factor scoring systems alone. Single-photon emission computed tomography,
      stress echocardiography, and possibly EBCT or multi-slice computed tomography,
      are emerging as valuable diagnostic tools for identifying asymptomatic diabetic
      patients who might require early and aggressive intervention to manage their
      cardiovascular risk.

PMID- 16904546
TI  - Screening asymptomatic diabetic patients for coronary artery disease: why not?
AB  - Given the elevated risk of cardiovascular events and the higher prevalence of
      silent coronary artery disease (CAD) in diabetic versus non-diabetic patients,
      screening asymptomatic diabetic patients for CAD is an appealing concept.
      However, many factors argue against implementing a broad-based screening program
      at the present time. Foremost is the lack of any published data demonstrating
      that a prospectively applied screening program improves outcome in asymptomatic
      diabetic patients. The true prevalence of CAD, and in particular prognostically
      important CAD, in this population is uncertain. Consensus documents recommend
      more aggressive treatment of hypertension and hyperlipidemia solely on the basis
      of diabetes status, without differentiation based on the presence or absence of
      identifiable CAD. There is no evidence that use of anti-ischemic medication can
      alter the natural history of CAD in these patients. Retrospectively performed
      studies using stress single-photon emission computed tomography (SPECT) imaging
      have reported that approximately 50% and 20% of patients have abnormal and high
      risk images, respectively. However, the only prospectively designed study, the
      DIAD (Detection of Ischemia in Asymptomatic Diabetics) study, reported a much
      lower percentage of abnormal SPECT images (16%) and images with a very large
      (>/=10% of the left ventricle) defect (1%). The financial implications of
      screening all asymptomatic diabetic patients determined to be at intermediate and
      high risk by clinical scoring systems is enormous. Clearly more data are needed
      to address this issue. Future studies should consider possible methods to enrich
      the patient subset that might benefit from screening and should include carefully
      performed cost-effective analyses.

PMID- 16904547
TI  - Myocardial scars more frequent than expected: magnetic resonance imaging detects
      potential risk group.
AB  - OBJECTIVES: The aim of this study was to investigate the prevalence of clinically
      recognized myocardial infarctions (RMIs) and unrecognized myocardial infarctions
      (UMIs) in 70-year-old subjects, assessed with magnetic resonance imaging (MRI),
      and to relate the findings to cardiac function and morbidity. BACKGROUND: Late
      enhancement MRI identifies myocardial scars and thereby has the potential to
      detect UMI. METHODS: Cardiac MRI was performed on 259 randomly chosen 70-year-old
      subjects. Late enhancement and cine sequences were acquired, and the ejection
      fraction and left ventricular (LV) mass were calculated. Late enhancement
      involving the subendocardial layer was considered to represent myocardial
      infarction (MI) scars, and their volumes were calculated. Information on cardiac
      morbidity and risk factors was collected from medical records and from a health
      examination. Subjects with MI scars, with or without a hospital diagnosis of MI
      were classified as RMI or UMI, respectively. RESULTS: The images from 248
      subjects (123 women, 125 men) were assessable. Myocardial infarction scars were
      found in 60 subjects (24.2%), in 49 of whom (19.8%) they were UMIs. The volumes
      of the UMIs were significantly smaller than those of the RMIs. There was an
      increased frequency of chest pain symptoms among the subjects with UMI or RMI
      compared with those without MI scars. Ejection fraction was significantly lower
      and LV mass significantly larger in the subjects with UMI or RMI than in those
      without MI scars. CONCLUSIONS: Unrecognized MI detected with MRI was more
      frequent than expected in 70-year-old subjects. The subjects displaying these
      UMIs may represent a previously unknown potential risk group for future
      cardiovascular events.

PMID- 16904548
TI  - Detection of transplant coronary artery disease using multidetector computed
      tomography with adaptative multisegment reconstruction.
AB  - OBJECTIVES: This study sought to determine whether multidetector computed
      tomography (MDCT) may be able to detect occlusive coronary disease in
      transplanted hearts. BACKGROUND: In heart transplant recipients, asymptomatic
      coronary disease requiring frequent surveillance commonly develops. Recent
      advancements in MDCT allow for noninvasive assessment of the coronary vessels.
      METHODS: Electrocardiogram-gated contrast-enhanced MDCT scans (16 x 0.75-mm
      detectors, 420 ms rotation, 100 ml contrast) with multisegment reconstruction
      were performed on 54 transplant recipients within 6 +/- 11 days of quantitative
      coronary angiography (QCA). Heart rate at the time of the scan was 90 +/- 11
      beats/min. Coronary arterial segments >1.5 mm in diameter were analyzed by
      independent investigators. RESULTS: There was a good correlation between MDCT and
      QCA percent stenosis (r = 0.75, p < 0.01, SEE = 15%). Of the 791 segments
      identified by QCA, 754 (95%) were analyzable by MDCT. The sensitivity,
      specificity, and positive and negative predictive values of MDCT compared with
      QCA for the detection of segments with significant (>50%) stenosis were 86%, 99%,
      81%, and 99%, respectively. The MDCT correctly identified 15 of the 16 (94%)
      transplant patients classified by QCA as having occlusive coronary artery disease
      and 29 of the 37 patients without significant stenosis (78%). In 1 patient who
      received intravenous beta-blockers, transient bradycardia requiring temporary
      pacing developed, but there were no other complications. CONCLUSIONS: Detection
      of occlusive coronary disease in heart transplant recipients with elevated
      resting heart rate by MDCT is feasible using multicycle reconstruction. The need
      for surveillance invasive coronary angiography in transplant recipients might be
      mitigated by use of MDCT.

PMID- 16904549
TI  - Left atrial volume predicts the risk of atrial fibrillation after cardiac
      surgery: a prospective study.
AB  - OBJECTIVES: This study sought to identify preoperative predictors of
      postoperative atrial fibrillation (POAF) among patients undergoing cardiac
      surgery. BACKGROUND: Postoperative atrial fibrillation is frequent after cardiac
      surgery and is associated with increased morbidity, mortality, prolonged hospital
      stay, and increased costs. Left atrial volume (LAV), a marker of chronically
      elevated left ventricular filling pressure, is a predictor of atrial fibrillation
      (AF) in the nonsurgical setting. METHODS: A total of 205 patients (mean age 62 +/
      16 years; 35% women) undergoing cardiac surgery were prospectively enrolled.
      Clinical risk factors were obtained by detailed medical record review and patient
      interview. Preoperative transthoracic echocardiograms were performed for
      assessment of LAV, left ventricular ejection fraction, and diastolic function.
      Follow-up was complete. Detection of POAF was based on documentation of AF
      episodes by continuous telemetry throughout hospitalization. RESULTS:
      Postoperative atrial fibrillation occurred in 84 patients (41.4%) at a median of
      1.8 days after cardiac surgery. The LAV was significantly larger in patients in
      whom AF developed (49 +/- 14 ml/m2 vs. 39 +/- 16 ml/m2, p = 0.0001). Patients
      with LAV >32 ml/m2 had an almost five-fold increased risk of POAF, independently
      of age and clinical risk factors (adjusted hazard ratio 4.84, 95% confidence
      interval 1.93 to 12.17, p = 0.001). Age and LAV were the only independent
      predictors of POAF. The area under the receiver-operator characteristics curve to
      predict POAF was 0.729 for LAV and 0.768 for the combination of LAV and age (both
      p < 0.0001). CONCLUSIONS: The LAV is a strong and independent predictor of POAF.
      Risk stratification using LAV and age enables clinicians to identify high-risk
      patients before cardiac surgery.

PMID- 16904550
TI  - Left atrial size and postoperative atrial fibrillation: the volume of evidence
      suggests it is time to break an old habit.

PMID- 16904551
TI  - Functional and structural vascular remodeling in elite rowers assessed by
      cardiovascular magnetic resonance.
AB  - OBJECTIVES: We aimed to noninvasively quantify the effects of chronic exercise
      training on both peripheral and central conduit artery function and structure
      with high-resolution magnetic resonance imaging (MRI). BACKGROUND: Physical
      activity has well-known beneficial effects on vascular function in subjects with
      endothelial dysfunction. Exercise also leads to beneficial effects on endothelial
      function in elderly athletes, possibly contributing toward the reduced risk from
      coronary artery disease in this age group. However, conflicting data exist on the
      training effects in the younger population. METHODS: A total of 49 young (age 20
      to 35 years) nonsmoking subjects, comprising elite rowers and age- and gender
      matched sedentary control subjects, underwent MRI (1.5-T). The ascending, the
      proximal descending, and the distal descending aorta, and the common carotid
      artery and the brachial artery were assessed for diastolic and systolic area and
      distensibility. Endothelial-dependent and -independent brachial artery dilatation
      were also assessed by cine MRI. RESULTS: Rowers showed vascular remodeling with
      enlarged brachial (by 51%, p < 0.001) and reduced central conduit artery cross
      sectional areas (by up to 28% [e.g., distal descending aorta], p < 0.001). Vessel
      distensibilities (mm Hg(-1)) were similar for elite rowers when compared with
      sedentary control subjects at all levels of the aorta and the carotid and
      brachial artery (p > 0.05 for all). Endothelial-dependent dilation (percentage
      and mm2) was similar for rowers and control subjects (p > 0.05). However, rowers
      showed reduced absolute (by 33%) endothelial-independent dilation (p < 0.001).
      CONCLUSIONS: Young elite rowers demonstrate normal endothelial-dependent but
      reduced endothelial-independent dilation. Chronic, whole body, combined endurance
      and strength-training does not lead to changes in arterial stiffness but to
      vascular remodeling.

PMID- 16904552
TI  - Cardiac electrophysiological consequences of neuromuscular incapacitating device
      discharges.
AB  - OBJECTIVES: The purpose of this study was to evaluate the cardiac consequences of
      neuromuscular incapacitating device (NID)/stun gun discharge in an experimental
      model. BACKGROUND: The large-voltage electrical discharges from NIDs have been
      suggested to pose a risk for triggering cardiac arrhythmias. METHODS:
      Intracardiac catheters and blood pressure transducers were inserted before the
      application of NID discharges in six anesthetized pigs. Two different
      commercially available models (NID-1 and NID-2), two different vectors of
      discharges (thoracic: parallel to the long axis of the heart on the chest wall,
      and nonthoracic: away from the chest, across the abdomen), and two different
      durations of discharge (5 and 15 s) were tested. The effect of simulated
      adrenergic stress using epinephrine was also evaluated. RESULTS: We studied a
      total of 150 discharges to 6 pigs; 74 of these discharges resulted in stimulation
      of the myocardium, as documented by electrical capture (mean ventricular rate
      during stimulation and capture, 324 +/- 66 beats/min). Of the 94 thoracic
      discharges, 74 stimulated the myocardium, compared with none from 56 nonthoracic
      discharges (p < 0.0001). During 16 discharges with epinephrine, there were 13
      episodes of stimulation of the myocardium, of which 1 induced ventricular
      fibrillation and 1 caused ventricular tachycardia. Thoracic discharges from NID-1
      were more likely to stimulate the myocardium than those from NID-2 (98% vs. 54%,
      p = 0.0007). CONCLUSIONS: In an experimental model, NID discharges across the
      chest can produce cardiac stimulation at high rates. This study suggests that
      NIDs may have cardiac risks that require further investigation in humans.

PMID- 16904553
TI  - Effects of cocaine intoxication on the threshold for stun gun induction of
      ventricular fibrillation.
AB  - OBJECTIVES: This study sought to assess cocaine's effects on Taser-induced
      ventricular fibrillation (VF) threshold in a pig model. BACKGROUND: Stun guns are
      increasingly used by law enforcement officials to restrain violent subjects, who
      are frequently intoxicated with cocaine and other drugs of abuse. The interaction
      of cocaine and the stun gun on VF induction is unknown. METHODS: We tested five
      adult pigs using a custom device built to deliver multiples of standard
      neuromuscular incapacitating (NMI) discharge that matched the waveform of a
      commercially available electrical stun gun (Taser X-26, Taser International,
      Scottsdale, Arizona). The NMI discharges were applied in a step-up and step-down
      fashion at 5 body locations. End points included determination of maximum safe
      multiple, minimum VF-inducing multiple, and ventricular fibrillation threshold
      (VFT) before and after cocaine infusion. RESULTS: Standard NMI discharges (x1)
      did not cause VF at any of the 5 locations before or after cocaine infusion. The
      maximum safe multiple, minimum VF-inducing multiple, and VFT of NMI application
      increased with increasing electrode distance from the heart. There was a 1.5- to
      2-fold increase in these values at each position after cocaine infusion,
      suggesting decreased cardiac vulnerability for VF. Cocaine increased the required
      strength of NMI discharge that caused 2:1 or 3:1 ventricular capture ratios at
      all of the positions. No significant changes in creatine kinase-MB and troponin-I
      were seen. CONCLUSIONS: Cocaine increased the VFT of NMI discharges at all dart
      locations tested and reduced cardiac vulnerability to VF. The application of
      cocaine increased the safety margin by 50% to 100% above the baseline safety
      margin.

PMID- 16904554
TI  - Temporary pulmonary stent placement as emergency treatment of pulmonary embolism:
      first experimental evaluation.
AB  - OBJECTIVES: We aimed to evaluate the performance of a newly designed temporary
      stent device as a percutaneous emergency treatment of pulmonary embolism.
      BACKGROUND: If thrombolysis is contraindicated or recanalization by thrombolysis
      delayed in patients with severe pulmonary embolism who are threatened by acute
      circulatory failure, percutaneous temporary pulmonary stent placement may
      represent an additional option before surgical embolectomy is considered.
      METHODS: The newly designed temporary pulmonary stent is made from woven Nitinol
      and has a distal blunt end and a proximal crimped end, which is firmly fixed to a
      0.035-inch guidewire. It is delivered through a 9.5-F polytetrafluoroethylene
      sheath using a pusher tube. Stent placement and removal were examined in 9
      anesthetized sheep with experimentally induced pulmonary embolism. Hemodynamic
      parameters were recorded in 7 animals. RESULTS: Delivery and removal of the stent
      was uneventful and rapidly accomplished. Stent placement was associated with a
      significant decrease in Miller angiographic index (from 11.2 +/- 3.1 to 3.8 +/-
      1.9; p = 0.0001), heart rate (from 139 +/- 35 beats/min to 92 +/- 11 beats/min; p
      = 0.0129), and mean pulmonary artery pressure (from 32 +/- 14 mm Hg to 21 +/- 14
      mm Hg; p = 0.0029) and a significant increase in mean aortic pressure (from 48 +/
      14 mm Hg to 61 +/- 8 mm Hg; p = 0.0080). Autopsy revealed neither wall damage
      nor parenchymal hemorrhage. CONCLUSIONS: Our preliminary study proves the
      technical feasibility of temporary placement and removal of a newly designed
      dedicated pulmonary stent to recanalize centrally located embolic occlusions in
      severe pulmonary embolism. Animal experimental evaluation revealed rapid and
      significant circulatory improvement after stent placement.

PMID- 16904555
TI  - Cyclooxygenase-2 inhibitors enhance shear stress-induced platelet aggregation.
AB  - OBJECTIVES: We aimed to investigate the effect of parecoxib, a selective
      cyclooxygenase-2 (COX-2) inhibitor, on in vivo shear stress-induced platelet
      aggregation in a rat model of arterial bypass with focal narrowing. BACKGROUND:
      Long-term use of COX-2 inhibitors is associated with increased incidence of
      adverse cardiovascular events, especially in patients with a history of
      cardiovascular disease. These patients are at risk for thrombotic occlusion of
      arterial stenoses initiated by shear stress-induced platelet aggregation.
      METHODS: To mimic the combination of a tight arterial stenosis and high shear
      stress in rats, an extracorporeal shunt from carotid to femoral artery was
      compressed by the rollers of a pump. Platelet aggregation was continuously
      measured by a photometric detector in the shunt. RESULTS: Pretreatment with
      parecoxib (20 mg/kg) almost doubled shear stress-induced platelet aggregation
      (188% vs. 100% in control subjects, p = 0.0003). This was accompanied by a fall
      in plasma 6-keto-prostaglandin F(1alpha) from 100 +/- 25 pg/ml to 36 +/- 11 pg/ml
      (p < 0.0001). Enhanced platelet aggregation was also observed with high-dose
      aspirin (150 mg/kg) (146%; p = 0.02) but not with low-dose aspirin (25 mg/kg),
      which reduced aggregation (68%; p = 0.01). The effect of parecoxib was
      neutralized by low-dose (1 mg/kg) clopidogrel (from 188% to 92%; p = 0.0001), but
      not by low-dose aspirin (from 188% to 177%; p = NS). CONCLUSIONS: In the presence
      of an arterial stenosis, COX-2 inhibitors enhance shear stress-induced platelet
      aggregation. This enhancement was prevented by low-dose clopidogrel but not by
      low-dose aspirin. Clopidogrel might therefore allow COX-2 inhibitors to be used
      without raising risk of thrombotic occlusion.

PMID- 16904556
TI  - EUK-8, a superoxide dismutase and catalase mimetic, reduces cardiac oxidative
      stress and ameliorates pressure overload-induced heart failure in the harlequin
      mouse mutant.
AB  - OBJECTIVES: The purpose of this study was to identify apoptosis-inducing factor
      (AIF) as a cardiac mitochondrial antioxidant and assess the efficacy of EUK-8, a
      salen-manganese catalytic free radical scavenger, to protect the AIF-deficient
      myocardium against pressure overload. BACKGROUND: Oxidative stress has been
      postulated to provoke cell death and pathologic remodeling in heart failure. We
      recently characterized the apoptosis-inducing factor-deficient harlequin (Hq)
      mouse mutant to display excessive pressure overload-induced oxidative stress,
      cell death, accelerated progression to heart failure, and a reduced capacity of
      subsarcolemmal mitochondria to scavenge free radicals, suggesting a role for AIF
      as a novel mitochondrial antioxidant. METHODS: Oxidative stress-sensitized Hq
      mutant mice and their wild-type (WT) counterparts were given low-dose EUK-8 (25
      mg/kg/day), an antioxidant with superoxide dismutase, catalase, and oxyradical
      scavenging properties, or vehicle for 4 weeks, and subjected to pressure overload
      (transverse aortic constriction) for 4 weeks. Myocardial geometry and function
      was serially assessed by echocardiography. RESULTS: EUK-8 ameliorated survival in
      Hq and WT mice subjected to pressure overload. EUK-8 also improved left
      ventricular end-systolic dimensions and fractional shortening, prevented
      myocardial oxidant stress, attenuated necrotic and apoptotic cell death, and
      attenuated cardiac hypertrophy and fibrosis in both mutant and WT mice.
      CONCLUSIONS: The protection against pressure overload-induced heart failure in Hq
      mice by EUK-8 substantiates the notion that AIF functions as an important
      mitochondrial antioxidant in the heart. Furthermore, because antioxidant
      treatment protected both the oxidative stress-prone Hq mouse model and WT mice
      against pressure overload-induced maladaptive left ventricular remodeling and
      cardiac decompensation, it may be useful as a novel therapeutic tool in the
      treatment of human heart failure.

PMID- 16904557
TI  - Effects of normal, pre-hypertensive, and hypertensive blood pressure levels on
      progression of coronary atherosclerosis.
AB  - OBJECTIVES: The purpose of this study was to evaluate the effects of normal blood
      pressure (BP), pre-hypertension, and hypertension on progression of coronary
      atherosclerosis. BACKGROUND: The Seventh Report of the Joint National Committee
      on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure
      (JNC-7) classifies BP as normal, pre-hypertension, and hypertension. The effects
      of these categories on progression of coronary atherosclerosis are unknown.
      METHODS: The 274 patients who completed the intravascular ultrasound (IVUS)
      substudy of the CAMELOT (Comparison of Amlodipine Versus Enalapril to Limit
      Occurrences of Thrombosis) trial were included. The entry criteria were > or =1
      angiographic coronary stenosis >20% and diastolic BP <100 mm Hg. Patients
      underwent a baseline coronary IVUS, which was repeated after 2 years of
      amlodipine, enalapril, or placebo therapy. The BP was evaluated periodically, and
      the averages of the measurements were used in the analyses. RESULTS: Mean BP
      throughout the study was 127.0 +/- 12.0/75.5 +/- 6.8 mm Hg. In multivariable
      analysis, significant determinants of progression included systolic BP (r = 0.16;
      p = 0.006) and pulse pressure (r = 0.14; p = 0.02). Patients with "hypertensive"
      average BP had a 12.0 +/- 3.6 mm3 (least-square mean +/- SE) increase in atheroma
      volume, those with "pre-hypertensive" BP had no major change (0.9 +/- 1.8 mm3),
      and those with "normal" BP had a decrease of 4.6 +/- 2.6 mm(3) (p < 0.001 by
      analysis of covariance; p < 0.05 for comparison of all pairs). CONCLUSIONS: The
      most favorable rate of progression of coronary atherosclerosis is observed in
      patients whose BP falls within the "normal" JNC-7 category (i.e., systolic BP
      <120 mm Hg and diastolic BP <80 mm Hg). This study suggests that in patients with
      coronary artery disease, the optimal BP goal may be substantially lower than the
      <140/90 mm Hg level.

PMID- 16904558
TI  - Optimal blood pressure levels in patients with coronary artery disease.

PMID- 16904559
TI  - Separation and renewal.

PMID- 16904560
TI  - Time-dependent cardiac chimerism in gender-mismatched heart transplantation
      patients.

PMID- 16904561
TI  - Measuring effects of antiatherosclerotic therapies.

PMID- 16904562
TI  - Aspirin resistance and atherothrombotic disease.

PMID- 16904564
TI  - The Emperor's new clothes are loose: lower body mass index, not calorie
      restriction, accounts for improved diastolic function.

PMID- 16904567
TI  - Implications and controversies of recent hypertension trials.

PMID- 16904569
TI  - Noninvasive home telemonitoring: the Trans-European Network-Home-Care Management
      System.

PMID- 16904570
TI  - Keeping apples and oranges separate: reassessing clinical trials that use
      composite end points as their primary outcome.

PMID- 16904573
TI  - Pleiotropic effects of statins and early benefit in the PROVE IT-TIMI-22 study.

PMID- 16904575
TI  - Microsurgical dissection of the carpal tunnel with respect to neurovascular
      structures at risk during endoscopic carpal tunnel release.
AB  - PURPOSE: The goal of this descriptive study was to investigate the anatomy of the
      carpal tunnel with respect to the related neurovascular structures, because a
      detailed knowledge of the complex anatomy of this region is essential to perform
      endoscopic carpal tunnel release. METHODS: Sixteen fresh-frozen cadaveric hands
      were used for the study. Dissection of the palmar aspect of the hand was
      performed by use of magnifying loupes, an operative microscope, and microsurgical
      instruments. All anatomic components were photographed, and dimensions were
      recorded by use of a micrometer. The distance from the radial aspect of the os
      pisiformis and the proximal and distal portals to the main structures that may be
      injured was measured. Topography of the transverse ligament and possible
      adhesions to the tendons and median nerve were also recorded. RESULTS: The mean
      distance from the radial aspect of the os pisiformis to the radial border of
      Guyon's canal and the ulnar edge of the palmaris longus tendon was 10.3 mm
      (range, 9 to 12 mm) and 16.1 mm (range, 12 to 22 mm), respectively. The mean
      distance from the distal portal to the superficial palmar arch and the ulnar
      artery was 10.4 mm (range, 5 to 15 mm) and 7.6 mm (range, 4.5 to 9 mm),
      respectively. The mean distance from the distal edge of the transverse ligament
      to the thenar branch of the median nerve was 2.7 mm (range, 0 to 4.1 mm). The
      mean length of the transverse ligament was 31 mm (range, 25 to 34.5 mm). In 14
      hands we also identified the palmaris longus tendon. In 11 hands we found
      adhesions between the transverse ligament and the sheath of the flexor tendons.
      CONCLUSIONS: The palmaris longus can be used as a guide for the placement of the
      proximal portal. Staying at the ulnar side of the palmaris longus keeps the
      superficial palmar branch of the median nerve at a safe distance from the
      instruments. The "fat drop sign" is also a useful guide for the placement of the
      distal margin of the transverse carpal ligament, keeping the distal portal away
      from the superficial palmar arch. Synovial adhesions can usually cover the
      inferior surface of the transverse ligament, and they need to be removed for
      clear endoscopic identification of the transverse fibers before the ligament is
      cut. CLINICAL RELEVANCE: Detailed knowledge of the complex anatomy of the carpal
      tunnel is essential to perform endoscopic carpal tunnel release.

PMID- 16904574
TI  - ACC/AHA/ESC 2006 guidelines for the management of patients with atrial
      fibrillation--executive summary: a report of the American College of
      Cardiology/American Heart Association Task Force on Practice Guidelines and the
      European Society of Cardiology Committee for Practice Guidelines (Writing
      Committee to Revise the 2001 Guidelines for the Management of Patients With
      Atrial Fibrillation).

PMID- 16904576
TI  - Chondrolysis after continuous intra-articular bupivacaine infusion: an
      experimental model investigating chondrotoxicity in the rabbit shoulder.
AB  - PURPOSE: Postoperative pain pumps are increasingly used to deliver a continuous
      infusion of local anesthetic into the surgical wound or the joint. Recently,
      there have been concerns that the use of such devices may be associated with
      chondrotoxicity and even cases of chondrolysis in the shoulder. An experimental
      model is presented that investigates potential chondrotoxic effects of a
      continuous intra-articular infusion of bupivacaine in the rabbit shoulder.
      METHODS: We divided 30 rabbits into 3 groups that received continuous infusions
      of either saline solution, bupivacaine, or bupivacaine with epinephrine into the
      glenohumeral joint over a period of 48 hours. Animals were killed after 1 week,
      and osteochondral and synovial samples from the glenohumeral joint underwent
      analyses with confocal microscopy for live/dead cell assay, metabolic sulfate
      uptake assessment, and conventional histologic analysis. RESULTS: Infusion of
      bupivacaine with epinephrine and without epinephrine decreased sulfate uptake by
      56% (P = .009) and 50% (P = .02), respectively, when compared with saline
      solution; cell viability decreased by 20% (P = .08) and 32% (P = .02),
      respectively. Histologic analysis yielded significantly worse scores for
      bupivacaine infusion with epinephrine (P = .004) and without epinephrine (P =
      .02). The results for bupivacaine with or without epinephrine were not
      significantly different. CONCLUSIONS: Continuous intra-articular infusion of
      bupivacaine with and without epinephrine led to significant histopathologic and
      metabolic changes in articular cartilage. CLINICAL RELEVANCE: Bupivacaine showed
      profound chondrotoxic effects in an experimental model that closely followed the
      current clinical application of postoperative pain pumps. The results caution
      against the use of such devices in applications for smaller joints with minimal
      clearance or dilution as a result of hematoma, where continuous exposure of
      cartilage to bupivacaine is expected.

PMID- 16904577
TI  - Long-term absorption of poly-L-lactic Acid interference screws.
AB  - PURPOSE: To evaluate the long term in vivo degradation of poly-L-lactic acid
      (PLLA) interference screws with computed tomography (CT) and radiography as used
      in patellar tendon autograft anterior cruciate ligament (ACL) reconstruction.
      METHODS: A total of 20 patients who had undergone patellar tendon autograft ACL
      reconstruction fixed with PLLA screws at least 7 years earlier were evaluated by
      physical examination, radiography, and CT to determine whether PLLA screw
      reabsorption and bone ingrowth had occurred. This study was granted Institutional
      Review Board approval. Lysholm, Tegner, Cincinnati, and International Knee
      Documentation Committee (IKDC) scores were obtained. CT data were measured in
      Hounsfield units. RESULTS: In all, 15 men and 5 women were evaluated 104 months
      after surgery (range, 89 to 124 months). CT and radiography demonstrated that the
      bone plug had fused to the tunnel wall, and that no intact interference screw was
      left. A parallel, threaded, and corticated screw tract was visible adjacent to
      the bone plug. No bone ingrowth had occurred at the screw site, although,
      occasionally, minimal calcification was seen. This was never as dense as
      cancellous bone, and no trabeculae were ever present. No positive pivot-shift
      test results were obtained. Lysholm, Tegner, and Cincinnati scores were 83, 5.6,
      and 75, respectively, at follow-up. Average KT difference was 0.7 mm. DISCUSSION:
      PLLA interference screws completely degraded, and the resulting area demonstrated
      a low Hounsfield count, consistent with soft tissue 7 years after insertion. No
      significant bone ingrowth occurred at the screw site. Femoral and tibial ACL
      tunnels were absent of anything but fibrous tissue and usually had a sclerotic
      cortical lining. CONCLUSION: PLLA biodegradable ACL screws eventually disappear
      completely. PLLA material is not replaced by bone. ACL graft tunnels are filled
      with nonossified material. This study provides a baseline for comparison with
      other biodegradable interference screws that may encourage bone ingrowth as they
      degrade. LEVEL OF EVIDENCE: Level IV (no or historical control).

PMID- 16904578
TI  - Biomechanical characteristics of 10 arthroscopic knots.
AB  - PURPOSE: To determine the optimal arthroscopic slip knot through comparison of
      ease of placement, loop security, knot security, and amount of suture material
      needed. METHODS: Ten commonly used arthroscopic knots (Dines knot, Duncan loop,
      Field knot, Giant knot, Lieurance Modified Roeder knot, Nicky's knot, SMC knot,
      Snyder knot, Tennessee slider, Weston knot) were tested. Ten knots were tied with
      No. 2 Ethibond (Ethicon, Somerville, NJ) for each testing mode trial. Each knot
      was tested with the Instron materials testing machine (Instron, Norwood, MA) for
      (1) forward and backward sliding characteristics; (2) loop security prior to
      securing with half-hitches (by assessing load); (3) resistance to sliding; (4)
      knot security after securing with 3 alternating half-hitches on alternating posts
      (by assessing ultimate load); (5) resistance to sliding; (6) distance to failure;
      and (7) knot weight, to evaluate for amount of suture material needed. Analysis
      of variance (P < .05) was used to compare different knots, and the knot with
      superior characteristics in most categories was selected as the best knot.
      RESULTS: The Dines knot performed best, exhibiting superior biomechanical
      characteristics in 6 of 7 measured categories. The only category in which the
      Dines knot did not perform superiorly was forward sliding, indicating that the
      Dines knot can be rated as intermediate in ease of placement. CONCLUSIONS: Once
      in place, the Dines knot provides superior loop security and knot security, with
      use of less suture material. CLINICAL SIGNIFICANCE: This study comprehensively
      analyzed 10 commonly used arthroscopic knots and identified the one that
      exhibited the best characteristics.

PMID- 16904579
TI  - Comparison of suture welding and hand-tied knots in mini-open rotator cuff
      repair.
AB  - PURPOSE: This study was undertaken to compare the results of mini-open rotator
      cuff repair with outcomes attained with hand-tied knots and suture welds.
      METHODS: A total of 50 consecutive patients treated by a single surgeon with mini
      open cuff repair and suture welding were retrospectively evaluated and compared
      with 55 consecutive patients treated with mini-open cuff repair and hand-tied
      knots. The groups were similar in terms of age, sex, hand dominance, and
      preoperative duration of symptoms. All procedures were performed in a hospital
      outpatient surgery center with patients in a lateral decubitus position under
      general anesthetic. Glenohumeral arthroscopy and arthroscopic acromioplasty were
      performed in all cases. Rotator cuff tears were repaired through enlargement of
      the lateral portal. All patients were evaluated before and after surgery with the
      University of California Los Angeles (UCLA) Shoulder Scale. RESULTS: In all, 47
      of 50 patients treated with suture weld were available for evaluation, with an
      average follow-up of 26 months. Preoperative UCLA scores averaged 12.5, and
      postoperative scores averaged 29.6. Of 55 patients treated with hand-tied knots,
      40 were available, with an average follow-up of 28 months. Preoperative UCLA
      scores averaged 13.2, and postoperative scores averaged 31.5. CONCLUSIONS: No
      statistical difference in postoperative UCLA scores was noted between the 2
      groups (P = .297). LEVEL OF EVIDENCE: Level III, retrospective comparative study.

PMID- 16904580
TI  - The strength of suture configurations in arthroscopic rotator cuff repair.
AB  - PURPOSE: This study evaluated the strength of different suture configurations
      with the use of a recently introduced arthroscopic suture passer (ExpressSew;
      Surgical Solutions, Valencia, CA). METHODS: The ultimate tensile strength and
      mode of failure of each suture configuration were repeatedly tested on a
      validated porcine rotator cuff tendon model, with the use of standard suture
      material (No. 2 FiberWire [Arthrex, Naples, FL]) passed with ExpressSew and
      tested on a Hounsfield digital tensiometer type H20K-W (Tinius Olsen, Hersham,
      PA). RESULTS: The strongest construct was 2 mattress sutures (mean, 169 N;
      standard deviation, 56.1 N); this was followed in strength by a single modified
      Kessler suture (mean, 161 N; standard deviation, 16.9 N), 4 simple sutures (mean,
      155 N; standard deviation, 27.3 N), and finally, a single Mason-Allen suture
      (mean, 140 N; standard deviation, 28.6 N). CONCLUSIONS: Study results show little
      difference in strength for varying complexities of suture configurations. In
      simple terms, no demonstrable difference was seen in the strength of construct,
      whether the surgeon used 4 simple sutures, 2 mattress sutures, or 1 grasping
      suture. CLINICAL RELEVANCE: This study allows the surgeon to justify use of the
      simplest configuration of suture passage that works in his hands, for the purpose
      of attaining a reliable and repeatable repair of the rotator cuff through
      arthroscopic methods.

PMID- 16904581
TI  - Functional outcomes of arthroscopic capsular release of the elbow.
AB  - PURPOSE: Elbow contracture is a common and difficult problem to manage. The
      purpose of this study was to determine the functional outcomes of arthroscopic
      capsular release in the management of elbow contractures. METHODS: A total of 22
      patients (14 males, 8 females; mean age, 42 years) undergoing arthroscopic
      contracture release were retrospectively reviewed at a minimum follow-up of 1
      year (mean, 25 months). In all, 20 patients had a capsulectomy, and 2 underwent
      capsulotomy. Patient-rated questionnaires (Disability of the Arm, Shoulder, and
      Hand questionnaire [DASH], American Shoulder and Elbow Surgeons Elbow Form [ASES
      e], and Short Form-36 [SF-36]) and clinical, radiographic, and objective
      evaluations were used to assess outcomes. Motion and strength were measured by
      independent evaluators through standard goniometry and the LIDO Isokinetic System
      (Loredan Biomedical, West Sacramento, CA). RESULTS: Mean flexion significantly
      improved from 122 degrees +/- 15 degrees to 141 degrees +/- 12 degrees (P <
      .001). Mean extension significantly improved from 38 degrees +/- 18 degrees to 19
      degrees +/- 13 degrees (P < .001). Mean arc improvement was 38 degrees +/- 23
      degrees (P < .001). None of the patients had instability, and no major
      neurovascular complications were reported. All patients had improved elbow
      function with a mean ASES-e score of 31 out of 36. Most patients were satisfied
      with their surgery, experienced minimal pain, and exhibited minimal impairment on
      the DASH. CONCLUSIONS: Arthroscopic debridement and capsulectomy of the
      contracted elbow is effective. Results are comparable with those of other reports
      in the literature in which both arthroscopic and open methods were used. LEVEL OF
      EVIDENCE: Level IV.

PMID- 16904582
TI  - Arthroscopic mobilization for contracture of the wrist.
AB  - PURPOSE: We evaluated the clinical efficacy of arthroscopic mobilization of the
      wrist for release of persistent traumatic contracture. METHODS: We
      retrospectively reviewed 11 consecutive patients who had undergone arthroscopic
      mobilization after trauma. Patients included 9 men and 2 women who ranged in age
      from 16 to 65 years (mean, 40 years). Injuries causing contracture included 8
      fractures of the distal radius, 1 Galeazzi fracture, 1 perilunate dislocation,
      and 1 carpal bone contusion. A single radiocarpal septum extended from the
      proximal fibrocartilage of the scapholunate ligament to the midradial ridge in
      all but 1 patient, in whom multiple fibrous bands bridged the radiocarpal joint.
      RESULTS: Arthroscopy disclosed 3 types of radiocarpal septum-a single
      fibromembranous structure that completely divided the joint (type A) in 9 cases,
      a membranous structure with a fenestration that partially divided the joint (type
      B) in 1 case, and multiple bands that completely divided the joint (type C); the
      latter situation occurred in the last patient described earlier. Preoperatively,
      the arc of motion averaged 76 degrees compared with an average of 98 degrees .
      Postoperatively, a 22 degrees increase was noted. CONCLUSIONS: Arthroscopic
      release of a radiocarpal septum was effective in improving range of wrist motion
      in patients with this finding. LEVEL OF EVIDENCE: Level IV, therapeutic case
      series.

PMID- 16904583
TI  - Time-related changes in the cross-sectional area of the tibial tunnel after
      compaction of an autograft bone dowel alongside a hamstring graft.
AB  - PURPOSE: Extensive tunnel expansion in hamstring anterior cruciate ligament (ACL)
      reconstruction can complicate revision surgery. The purpose of this study was to
      examine our hypothesis that compaction of a bone dowel into the tibial tunnel
      reduces the cross-sectional area of the tunnel on the day of surgery and limits
      tunnel expansion to that of the cross-sectional area of the reamer at 4 months
      and 1 to 2 years. METHODS: A bone dowel averaging 23 mm in length and 7 mm in
      diameter was harvested from the tibial tunnel in 10 patients undergoing hamstring
      ACL reconstruction. The tibial tunnel was dilated, and the bone dowel was
      compacted anterior to the tendon graft. The cross-sectional area of the tibial
      tunnel was calculated on the day of surgery and at 4 months and 1 to 2 years
      postoperatively from computed tomography scans. RESULTS: On the day of surgery,
      the cross-sectional area of the tibial tunnel was 34% smaller than the 50-mm2
      cross-sectional area of the 8-mm reamer used to drill the tunnel (P < .001). At 1
      to 2 years, the cross-sectional area of the tibial tunnel was smaller than that
      of the reamer in 6 subjects, was slightly larger (53 to 56 mm2) in 3 subjects,
      and was substantially larger (80 mm2) in 1 subject. CONCLUSIONS: A surgeon who
      compacts an autogenous bone dowel into the tibial tunnel alongside a hamstring
      graft can expect little to no tunnel expansion in 90% of patients at 1 to 2
      years. To our knowledge, the limitation of tunnel expansion to that of the cross
      sectional area of the reamer has not been shown with other tibial fixation
      techniques. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

PMID- 16904584
TI  - Generalized joint laxity and contralateral patellar hypermobility in unilateral
      recurrent patellar dislocators.
AB  - PURPOSE: The purpose of this study was to assess the relation between generalized
      joint laxity and patellar hypermobility in unilateral recurrent patellar
      dislocators. TYPE OF STUDY: Case series. METHODS: A total of 82 patients (23 male
      and 59 female patients) with unilateral recurrent patellar dislocation were
      studied compared with an age- and sex-matched control group. The modified Carter
      and Wilkinson criteria for generalized joint laxity and lateral patellar
      hypermobility test were examined. RESULTS: Generalized joint laxity (score of 4
      or 5) was present in 20 patients (24%) with recurrent patellar dislocation in 8
      subjects (10%) of the control group. The mean total score was 2.5 (SD, 1.4) in
      the recurrent patellar dislocators and 1.7 (SD, 1.3) in the control group. The
      incidence of generalized joint laxity (P = .013) and the mean total score (P =
      .00004) were statistically significant between the two groups. A hypermobile
      patella was present in 42 patients (51%) and in 5 subjects (6%) of the control
      group. There was a large statistically significant difference between the two
      groups (P < .00001). CONCLUSIONS: Although a hypermobile patella and generalized
      joint laxity were significant between the recurrent patellar dislocators and the
      control group, a hypermobile patella was more significant than generalized joint
      laxity as the predisposing factors of patellar dislocation. LEVEL OF EVIDENCE:
      Level IV, prognostic case series.

PMID- 16904585
TI  - Transient bone marrow edema syndrome of the knee: clinical and magnetic resonance
      imaging results at 5 years after core decompression.
AB  - PURPOSE: We report on 24 cases of transient bone marrow edema syndrome in 18
      patients who underwent core decompression of the knee. METHODS: Diagnosis was
      made with the use of radiographs, magnetic resonance imaging (MRI), and core
      biopsy testing. Arthroscopic surgery and core decompression were carried out in
      all patients, and MRI was performed again, 5 years after surgery was performed.
      RESULTS: Medial and lateral femoral condyles were affected in 15 and 7 knees,
      respectively. In all, 6 patients presented with bilateral involvement of the
      knees (migrating transient bone marrow edema syndrome). Two of these patients had
      affections of the medial and lateral compartments within the same knee at
      different times, consistent with intra-articular regional bone marrow edema
      syndrome. Core biopsy specimens showed areas of bone marrow edema and vital
      trabeculae covered by osteoblasts and osteoid seams. Resolution of symptoms and
      normalization of MRI findings occurred in all patients within 12 weeks after
      surgery. CONCLUSIONS: Migrating bone marrow edema was found in a high percentage
      (33%) of patients at 5-year follow-up; however, all patients were clinically
      asymptomatic, and signal alterations on MRI had resolved completely. The high
      incidence of migrating bone marrow edema, the lack of osteonecrotic regions in
      our specimens, and the fact that none of these cases progressed to spontaneous
      osteonecrosis seem to further support the contention that bone marrow edema
      syndrome of the knee is a distinct entity. LEVEL OF EVIDENCE: Level II,
      diagnostic study; development of diagnostic criteria on the basis of consecutive
      patients and with universally applied reference gold standard.

PMID- 16904586
TI  - Meniscus-stabilizing function of the meniscofemoral ligament: experimental study
      of pig knee joints.
AB  - PURPOSE: To demonstrate experimentally, with the use of pig knee joints, that the
      posterior meniscofemoral ligament (PML) stabilizes the lateral meniscus (LM).
      METHODS: Amputated stumps of the knee joints of Yorkshire pigs, which are
      anatomically similar to human knee joints, were used. The PML was intact or was
      cut according to 1 of 6 different conditions: (1) intact PML with intact LM, (2)
      intact PML with a radial tear of the posterior horn of the LM, (3) intact PML
      with total lateral meniscectomy, (4) cut PML with intact LM, (5) cut PML with a
      radial tear of the posterior horn of the LM, and (6) cut PML with total lateral
      meniscectomy. Pressure-sensitive film was inserted beneath the lateral femoral
      condyle, an axial load of 150 kg was placed on the knee joint with a universal
      testing machine, and the pressed area and maximum and average pressures were
      measured with the Prescale Imaging Analysis System (Fujifilm Medical Systems,
      Stamford, CT). RESULTS: With an intact PML, no difference was seen between the
      intact meniscus and the radial tear of the posterior horn of the LM in pressed
      area and maximum and average pressures. With a cut PML, pressure concentration,
      detected as significantly reduced pressed area and increased maximum and average
      pressures, was observed, regardless of the condition of the LM. CONCLUSIONS: PML
      of the pig stabilized the LM under an axial load, and an intact PML yielded
      results similar to those observed in total lateral meniscectomy. Our findings
      suggest that posterior horn tears of the LM, which are rarely symptomatic, may be
      caused by stabilizing of the lateral meniscus by the PML against the load placed
      on the knee joint. CLINICAL RELEVANCE: Findings suggest that the PML, lateral
      side, stabilizes the LM when the ligament is intact. Even when a tear of the
      meniscus occurs, no increased localized pressure areas appear on the meniscus;
      this may explain why these tears are rarely symptomatic.

PMID- 16904587
TI  - Arthroscopic lateral meniscectomy in knees with lateral compartment
      osteoarthritis: a case series study.
AB  - PURPOSE: The purpose of this study was to investigate the intermediate-term
      postoperative results of arthroscopic surgery for lateral compartment
      osteoarthritis (OA) of the knee in a case series study. METHODS: In a series of
      30 knees in 29 patients who underwent arthroscopic surgery for lateral
      compartment OA, we were able to observe 25 joints in 24 patients prospectively
      for the entire postoperative period. The follow-up period ranged from 1 to 13
      years, with a mean of 5.5 +/- 3.7 years. The procedure in all cases comprised
      lateral partial meniscectomy with either abrasion arthroplasty, or debridement of
      the articular cartilage surface or microfracture. Of 25 cases, 13 underwent
      abrasion arthroplasty, 10 underwent debridement of the articular cartilage
      surface, and 2 underwent microfracture. Results were assessed by use of the
      postoperative knee score, findings of arthritic changes on plain knee
      radiographs, and other measurements of postoperative progress. RESULTS: Further
      surgery was required in 2 cases (8%) because of poor postoperative progress. In
      the remaining 22 patients, knee scores improved from a mean of 52.4 points
      preoperatively to 84.6 points postoperatively and mean function scores improved
      from 45.4 points to 82.6 points, with these favorable results being maintained at
      the last follow-up. The femoral-tibial angle decreased slightly as each year
      passed postoperatively. Radiologic progression of OA was seen at 3 years
      postoperatively in 7 patients (28%), but no progression was seen in 12 (48%). A
      positive correlation was seen between the preoperative femoral-tibial angle and
      postoperative results (R = 0.81, P < .01). CONCLUSIONS: When lateral compartment
      OA and lateral meniscal tears are both present, the clinical outcome of lateral
      meniscal resection was favorable. In patients with lateral compartment OA,
      therefore, an arthroscopic procedure, including meniscectomy, should be
      considered early. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

PMID- 16904588
TI  - A comparison of the effects of radiofrequency treatment and mechanical shaving
      for meniscectomy.
AB  - PURPOSE: The goal of this ex vivo pilot study was to compare radiofrequency
      treatment with cutting and shaving treatment of meniscal tears by use of a
      mechanical testing procedure and electron microscopy to establish the mechanical
      characteristics and qualitative appearance of meniscal tissue after the use of
      each of these procedures. METHODS: In this study 136 menisci were explanted and
      divided into 4 groups: a damaged, untreated control group; a group damaged in the
      same way as the control group and treated by mechanical shaving of the meniscal
      tear; a group damaged in a similar way and then treated by radiofrequency by use
      of a radiofrequency wand; and a fourth group in which plunge-cutting by use of
      the radiofrequency wand was used to resect the tissue, beginning at the superior
      surface of the meniscus in a place that corresponded to the location of the
      meniscal tears. The menisci were then tested for strength by applying radial
      tension to the tear. Electron microscopy at low and high magnification was used
      to evaluate the appearance of the surface of the menisci after shaving or
      radiofrequency treatment. RESULTS: Static mechanical testing to failure showed no
      significant difference between the control group and the 3 test groups. However,
      there was a statistically significant difference between the radiofrequency
      treated groups and the mechanically shaved group at the .033 level. On fatigue
      testing, there was no statistically significant difference in the failure cycles,
      but the coefficient of variation was 8 times greater for the mechanically shaved
      menisci versus the radiofrequency-treated menisci. Scanning electron microscopy
      showed that the mechanically treated menisci had flat surfaces with clefts or
      fissures. The radiofrequency-treated menisci had a homogeneous appearance without
      clefts. CONCLUSIONS: This study showed that radiofrequency-treated damaged tissue
      leaves a qualitatively different surface from the mechanically treated menisci,
      which failed at a significantly higher load on static testing. On fatigue
      testing, there was greater variation in the number of cycles to failure of
      mechanically treated specimens versus the radiofrequency-treated menisci.
      CLINICAL RELEVANCE: Although recurrent meniscal tears are uncommon, they may be
      of value in evaluating different methods of meniscectomy. This study points out
      mechanical and qualitative differences between shaved and radiofrequency-treated
      meniscectomy.

PMID- 16904589
TI  - Intra-articular drain versus no drain after arthroscopic anterior cruciate
      ligament reconstruction: a randomized, prospective clinical trial.
AB  - PURPOSE: A significant proportion of surgeons use intra-articular drains after
      arthroscopic anterior cruciate ligament (ACL) reconstruction. The usual reason
      given to justify the use of a drain is to minimize patient pain and stiffness of
      the knee joint. The purpose of this study was to assess the validity of this
      approach. METHODS: In this study 118 consecutive ACL reconstruction patients were
      randomized to no drain or a postoperative intra-articular suction drain.
      Inclusion criteria included a successful ACL reconstruction via either 4-strand
      hamstrings or bone-patellar tendon-bone autograft as a graft source. The primary
      outcomes were defined as pain (assessed by pain scores and analgesic counts) and
      range of motion (ROM) (assessed by loss of flexion and extension compared with
      the nonoperative leg). An independent statistical analysis was performed.
      RESULTS: The 2 groups were comparable with respect to patient demographics,
      surgical findings, and procedures performed. There were no differences between
      the treatment groups for the primary outcomes of pain and ROM during the 8-week
      follow-up period. The study had adequate power to detect a clinically significant
      difference. Regarding the secondary outcomes, there was a difference in the grade
      of hemarthrosis between the groups at week 1 but not at week 4 or 8. However, the
      difference in subjective grade of hemarthrosis at 1 week did not have any effect
      on the primary outcomes of pain and ROM. During the study period, there were no
      complications in either group. CONCLUSIONS: The routine use of intra-articular
      drains after arthroscopic ACL surgery was not supported by this study. LEVEL OF
      EVIDENCE: Level II, randomized controlled trial without narrow confidence
      intervals.

PMID- 16904590
TI  - The association between posterior-inferior tibial slope and anterior cruciate
      ligament insufficiency.
AB  - PURPOSE: The purpose of this study was to determine whether an increased
      posterior-inferior tibial slope (PITS) is associated with anterior cruciate
      ligament (ACL) rupture and whether an increased PITS results in worse pivot-shift
      grades in ACL-insufficient patients. This study also examined the difference in
      PITS between men and women. METHODS: We radiographically measured the PITS angle
      of 100 ACL-insufficient patients and 100 patients with patellofemoral pain
      (control patients). The mean PITS of male and female cases and control patients
      was compared to determine whether sex had an influence on the mean PITS angle.
      The measured PITS was compared with the pivot-shift grade with patients under
      anesthesia in a subgroup of 87 isolated ACL-insufficient patients with no other
      knee injury. RESULTS: Female ACL-insufficient patients had a significantly
      greater PITS (12.0 degrees +/- 3.5 degrees ) than their negative controls (8.6
      degrees +/- 2.7 degrees ) (P < .001). Male ACL-insufficient patients had a
      significantly greater PITS (10.8 degrees +/- 3.9 degrees ) than their negative
      controls (8.4 degrees +/- 3.4 degrees ) (P < .001). In the isolated ACL
      insufficient patients, the high-grade pivot-shift patient group had a
      statistically significantly greater PITS (11.10 degrees +/- 3.85 degrees ) than
      the low-grade pivot-shift patient group (9.19 degrees +/- 3.58 degrees ) (P =
      .03). CONCLUSIONS: An increased PITS is associated with ACL rupture. A higher
      pivot-shift grade is associated with an increased degree of PITS. Female patients
      did not have a significantly greater mean PITS angle than male patients. LEVEL OF
      EVIDENCE: Level III, prognostic case-control study.

PMID- 16904591
TI  - No-tunnel anterior cruciate ligament reconstruction: the transtibial all-inside
      technique.
AB  - The purpose of this technical note is to describe the transtibial all-inside
      anterior cruciate ligament (ACL) reconstruction technique. This technique
      combines the advantages of previously described but technically demanding all
      inside ACL reconstruction techniques with the ease and familiarity of transtibial
      guide pin placement. The all-inside technique uses bone sockets as opposed to
      bone tunnels in both the femur and the tibia and represents a "no-tunnel"
      technique. When performed with allograft tissue, the method requires only
      arthroscopic portals and percutaneous guide pin passage. In such cases, this
      represents a "no-incision" ACL reconstruction. The technique requires the use of
      a Dual Retrocutter (Arthrex, Naples, FL). This cannulated drill is placed via the
      anteromedial arthroscopic portal and threads onto a transtibial, percutaneous,
      reverse-threaded guide pin. Because the drill is assembled arthroscopically
      (within the joint), a skin incision is not required. The Dual Retrocutter is
      capable of retrograde and antegrade drilling. Thus, a single Dual Retrocutter
      achieves transtibial drilling of both tibial and femoral bone sockets. The
      transtibial all-inside technique may be performed with the use of any ACL graft
      option. Graft diameter should equal socket diameter. To prevent the graft from
      "bottoming-out" during tensioning and fixation, graft length must be less than
      the sum of combined femoral plus tibial socket lengths plus ACL intra-articular
      distance. During the learning curve, surgeons may choose to wait until the
      sockets have been prepared, so that graft length need not be estimated. If the
      graft is prepared before arthroscopic surgery is performed, a 79-mm graft length
      could be recommended as ideal. To prepare for graft passage, both femoral and
      tibial graft passing suture loops must be brought out the anteromedial
      arthroscopic portal without soft tissue interposition between or within the
      loops. To prepare for graft fixation, a nitinol wire must be brought into the
      joint via the transtibial, percutaneous guide pin tract for the purpose of
      guiding the introduction of a cannulated Retroscrewdriver. All of these goals may
      be accomplished in a single pass. The graft is fixed with femoral and tibial
      Retroscrews. Backup fixation is optional and may be achieved by tying sutures
      over small, percutaneously placed cortical buttons. Advantages of this technique
      may result from "anatomic" graft fixation at the levels of the femoral and tibial
      joint lines and from retrograde screw fixation, which may eliminate interference
      screw divergence and increase graft tension when the retrograde screw is
      advanced. Additionally, because this technique minimizes skin incisions and
      eliminates open bone tunnels, patients may experience decreased pain, more rapid
      return to function, and improved cosmesis.

PMID- 16904592
TI  - Arthroscopic treatment of septic arthritis of the hip.
AB  - Arthrotomy is considered standard treatment for septic arthritis of the hip; the
      procedure may be complicated by avascular necrosis or postoperative hip
      instability. Arthroscopic treatment of patients with this condition is still not
      an established technique, despite its minimally invasive nature and the fact that
      it is associated with low morbidity. A 3-portal arthroscopic technique by Byrd
      with the patient in the supine position was used for drainage, debridement, and
      irrigation in 6 patients with septic coxarthrosis. Continuous postoperative intra
      articular irrigation was not provided, nor were postoperative decompression
      drains used. All patients were treated with intravenous antibiotics for 3 weeks,
      followed by oral antibiotics for an additional minimum of 3 weeks. Patients were
      followed for 6 to 42 months. Staphylococcus aureus was identified in 4 of the 6
      patients. All patients had a rapid postoperative recovery. Mean Harris Hip Score
      at the last review was 97.5 points. All patients showed full range of motion of
      the affected hip. No complications occurred with this group of patients. Thus, 3
      directional arthroscopic surgery combined with large-volume irrigation is an
      effective treatment modality in cases of septic arthritis of the hip. It is less
      invasive than arthrotomy and offers low rates of postsurgical morbidity.

PMID- 16904593
TI  - Arthroscopic resection of the calcaneonavicular coalition or the "too long"
      anterior process of the calcaneus.
AB  - Calcaneonavicular coalition and the "too long" anterior process (TLAP) of the
      calcaneus can manifest as lateral foot pain, peroneal spastic flatfoot, and
      repeated ankle sprain. Surgical resection of the bone bar is frequently required.
      We present here an arthroscopic approach that can be used to accurately assess
      pathoanatomy and resect the bone bar. A portal is established slightly dorsal to
      the angle of Gissane. This is the primary visualization portal. The working
      portal, which is identified under an image intensifier, is located at the space
      between the talonavicular and calcaneocuboid joints, directly over the TLAP or
      the calcaneonavicular coalition. With the 2.7-mm 30 degrees arthroscope placed at
      the primary visualization portal, soft tissue around the TLAP or the
      calcaneonavicular coalition is cleared up with the use of an arthroscopic shaver
      at the working portal. After the TLAP or the calcaneonavicular coalition is
      clearly visualized, it can be resected with an arthroscopic burr through the
      working portal. The bone bar is resected proximally until the medial side of the
      calcaneocuboid joint, the lateral side of the taloavicular joint, and the plantar
      lateral aspect of the talar head are clearly seen. Inversion stress should then
      be applied to the foot to prevent further impingement of the anteromedial process
      of the calcaneus to the plantar-lateral part of the talar head.

PMID- 16904594
TI  - Reconstruction of the medial patellofemoral ligament with autologous quadriceps
      tendon.
AB  - In knees with insufficient or previously disrupted medial retinacular and
      patellofemoral ligaments caused by subluxation or dislocation, anatomic
      reconstruction of the medial patellofemoral ligament may be performed. This
      procedure involves harvesting of an 8 x 70-mm medial quadriceps tendon graft,
      which leaves the quadriceps tendon retinacular attachment intact and avoids
      patellar and femoral drill holes. This graft is passed beneath the retinaculum
      adjacent to the femoral epicondyle and is sutured to the medial intermuscular
      septum-a procedure that reproduces the medial patellofemoral ligament and is
      supported by imbrication of the remaining medial retinaculum. The tension of the
      graft and of the medial retinaculum is set at closure with the knee in 30 degrees
      to 45 degrees of flexion; this allows the patella to be moved a distance equal to
      25% of its width. Avoidance of drill holes allows the procedure to be used
      regardless of skeletal maturity and reduces fracture complications, inadequate
      graft placement, and failure of fixation. Postoperative rehabilitation includes
      immediate knee motion from 0 degrees to 90 degrees and partial weight bearing.

PMID- 16904595
TI  - A new noninvasive controlled intra-articular ankle distraction technique on a
      cadaver model.
AB  - Effective joint distraction is crucial in arthroscopic ankle surgery. We describe
      an effective and controlled intra-articular ankle distraction technique that we
      have studied by means of a fresh-frozen cadaver model. Using a kyphoplasty
      balloon, which is currently used in spine surgery, we tried to achieve a
      controlled distraction. After the fixation of the cadaver model, standard
      anteromedial and anterolateral portals were used for ankle arthroscopy. From the
      same portals, the kyphoplasty balloon was inserted and placed in an appropriate
      position intra-articularly. The necessary amount of distraction was achieved by
      inflating the kyphoplasty balloon with a pressure regulation pump. All anatomic
      sites of the ankle joint were easily visualized with the arthroscope during
      surgery by changing the pressure and the intra-articular position of the
      kyphoplasty balloon. Ankle distraction was clearly seen on the arthroscopic and
      image intensifier view. The kyphoplasty balloon is simple to place through the
      standard portals and the advantage is that it allows easy manipulation of the
      arthroscopic instruments from the same portal.

PMID- 16904596
TI  - Arthroscopic release of first metatarsophalangeal arthrofibrosis.
AB  - Various degrees of first metatarsophalangeal joint arthrofibrosis frequently
      occur in patients with bunion surgery or big toe trauma. In those patients with
      functional limitation who fail to respond to conservative treatment, surgery is
      indicated. We describe here an arthroscopic approach to first metatarsophalangeal
      release that is designed to improve functional results. Dorsomedial and
      dorsolateral portals are established at the medial and lateral sides of the
      extensor hallucis longus tendon. Through these 2 portals, the dorsal capsule is
      released and the medial and lateral joint gutters can be cleared up. The
      metatarsosesamoid compartment is approached through the straight medial portal
      and the working portal, the latter of which is located 4 cm proximal to the joint
      line between the abductor hallucis tendon and the medial head of the flexor
      hallucis brevis. Under visualization through the medial portal, adhesions around
      the sesamoid apparatus can be debrided with a shaver through the working portal.
      This completes the release of joint circumference and improves the motion range
      of the joint.

PMID- 16904597
TI  - Arthroscopic psoas tenotomy.
AB  - Tenotomy may be indicated for psoas tendinitis or painful snapping if
      conservative treatment remains unsuccessful. Because of significant complications
      with open techniques, endoscopic operations have been developed. We present a new
      arthroscopic technique to access and release the psoas tendon from the hip joint.
      This procedure can be performed in addition to other arthroscopic procedures of
      the hip joint or alone. To exclude additional hip disease, a diagnostic round of
      the joint should be completed. After hip arthroscopy of the central compartment
      has been performed, traction is released and the 30 degrees arthroscope is placed
      via the proximal anterolateral portal lying on the anterior femoral neck. The
      medial synovial fold can be identified. This fold lies slightly medially
      underneath the anteromedial capsule at the level of the psoas tendon. The
      arthroscope is turned toward the anterior capsule. Sometimes, the tendon shines
      through a thin articular capsule, or it may even be accessed directly via a hole
      connecting the hip joint and the iliopectineal bursa at the level of the anterior
      head-neck junction. If this cannot be done, an electrothermic probe is introduced
      via the anterior portal to make a 2-cm transverse capsular incision. The tendon
      is released with the back side of the electrothermic device turned to the iliacus
      muscle that lies anterior to the psoas tendon. A complete release is achieved
      when the tendon stumps can be seen gapping at a distance and the fibers of the
      iliacus muscle are visible. The first 9 patients who underwent surgery performed
      according to this technique developed no complications, and their hip flexion
      strength was restored to normal within 3 months.

PMID- 16904598
TI  - New meniscus repair technique for peripheral tears near the posterior tibial
      attachment of the posterior horn of the medial meniscus.
AB  - We introduce a suture technique to repair a peripheral tear near the posterior
      tibial attachment of the posterior horn. A suture hook was inserted through the
      posteromedial portal, and the peripheral capsular rim was penetrated from
      superior to inferior by the sharp hook. Both relay limbs were brought out through
      the posteromedial portal. The outer limb of the superior peripheral capsular rim
      was identified with a hemostat. An 18-gauge spinal needle loaded with a No. 0
      polydioxanone suture (PDS) was introduced into the joint from the anteromedial
      portal; it was passed through the joint space until it penetrated the inner torn
      meniscus. The PDS suture loaded within the needle was pushed into the joint and
      picked up through the posteromedial portal. The needle was pulled out of the torn
      meniscus and readvanced over it while the suture was kept loaded. The other limb
      of the suture from the tip of the spinal needle was retrieved through the
      posteromedial portal. The initial PDS suture limb was hooked to the shuttle-relay
      system; it then was passed through the inner torn meniscus and the peripheral
      capsular rim. The suture limb exiting from the peripheral capsular rim was used
      as a post and was joined to the other suture limb to form a sliding knot.

PMID- 16904599
TI  - Be aware of bone marrow edema syndrome in ankle arthroscopy: a case successfully
      treated with iloprost.
AB  - Bone marrow edema syndrome (BMES) is a nontraumatic syndrome characterized by
      disabling joint pain. The disease occurs especially in the hip joint, and the
      ankle joint has been reported in the English-language literature to be affected
      only rarely. We describe here the case of an adult with BMES in both ankle
      joints. She has been treated with nonsteroidal anti-inflammatory drugs and
      physical therapy, as well as ankle arthroscopy, all of which have been
      unsuccessful. BMES was diagnosed on the basis of clinical and magnetic resonance
      imaging (MRI) findings. The patient was treated with iloprost (Ilomedin; Schering
      AG, Berlin, Germany); the course of therapy consisted of 5 infusions of 40 microg
      of iloprost in 500 mL of sodium chloride solution, given over 6 hours on 5
      consecutive days. MRI at the third monthly visit showed nearly complete
      resolution of bone marrow edema. The patient was followed for 2 years and 6
      months and was completely asymptomatic. This case report suggests the need for
      orthopaedic surgeons to know about BMES. Before all-arthroscopic interventions
      are performed, MRI views should be evaluated carefully. Iloprost infusion therapy
      seems to be effective and safe in the management of BMES.

PMID- 16904600
TI  - Arthroscopic treatment for gouty tophi mimicking an intra-articular synovial
      tumor of the knee.
AB  - Tophi deposition is a well-recognized complication of chronic gout, but usually
      lacks obvious symptoms. Magnetic resonance imaging (MRI) findings may allow a
      relatively specific diagnosis to be rendered. In this study, we report an unusual
      case of gouty tophi presenting as an intra-articular synovial tumor of the knee,
      blocking the range of motion. We also describe its MRI appearance, which was
      compatible with the clinical suspicion. After arthroscopic excision of the
      "tumor," the patient was symptom free.

PMID- 16904601
TI  - False magnetic resonance imaging persistence of a biodegradable anterior cruciate
      ligament interference screw with chronic inflammation after 4 years in vivo.
AB  - Surgeons should be aware that the degradation kinetics of biodegradable implants
      likely influence the rate of osseous integration, and depend on numerous factors
      such as polymer weight, crystallinity, and stereocopolymer ratio. We present a
      case of inflammatory reaction at a polylactide tibial interference screw site
      more than 4 years after primary anterior cruciate ligament (ACL) reconstruction.
      This inflammation was presumptively treated as an infection with surgical
      irrigation and debridement. Preoperatively, the screw was clearly delineated by
      magnetic resonance imaging (MRI), yet was grossly absent at surgery.
      Postoperative MRI confirmed thorough debridement and complete absence of the
      screw. This report shows that not only can a late inflammatory reaction occur,
      after up to 4 years in vivo, but that the MRI may show a persistent screw despite
      significant biodegradation. False MRI-persistent screws should be considered when
      critically reviewing studies that use MRI in the methods for evaluating
      biodegradable implants. More importantly, false MRI-persistent screws may have
      significant ramifications when planning revision surgery after primary ACL
      reconstruction having used interference screws that can degrade over several
      years.

PMID- 16904602
TI  - Endoscopic evacuation of a hematoma resulting from strain injury of the medial
      head of the gastrocnemius muscle.
AB  - Strain of the medial head of the gastrocnemius muscle (GM) is a common injury
      that can be confirmed by ultrasound (US) or magnetic resonance imaging. We report
      a case of strain injury of the medial head of the GM, with a hematoma between the
      soleus muscle and the GM. US revealed an enlarged hypoechoic area between the
      soleus and the GM. By US-guided puncture, only a small amount of old blood was
      evacuated. Hence we undertook a surgical approach. It was performed under general
      endotracheal anesthesia, in the prone position. The most superficial area of
      hematoma was shown by US. A sharp 4-mm trocar was inserted in the posteromedial
      side of the calf and the hematoma was partially evacuated by suction. The cavity
      was washed out with saline solution. The arthroscope was then inserted. A second
      portal was made laterally and a shaver was inserted under optic control. The
      inflow pressure was not allowed to exceed 45 mm Hg. The shaver was used to remove
      blood coagula and fibrin septa that divided the cavity. The fibrous cavity
      membrane was debrided. By the end of the procedure, the circumference of the leg
      was reduced by 3 cm and the skin was softer on palpation. The patient was
      discharged the next day. One week after surgery, US examination revealed only a
      thin hypoechoic area in place of the previous collection. Two weeks after
      surgery, he was able to walk painlessly, and at 6 weeks he had regained normal
      walking activity.

PMID- 16904603
TI  - Our 25th anniversary-a milestone.

PMID- 16904604
TI  - Level V evidence: is it really the way forward?

PMID- 16904605
TI  - Intracellular signaling in tumor and endothelial cells: The expected and, yet
      again, the unexpected.
AB  - In this issue of Cancer Cell, Phung and coworkers demonstrate that sustained
      endothelial activation of Akt by expression of constitutively activated Akt1
      (myrAkt1) leads to blood vessels that essentially recapitulate the complex
      structural and functional abnormalities of tumor vessels. The authors provide
      evidence that rapamycin inhibition of PI3K/Akt/mTOR signaling in endothelial
      cells (ECs), by either reducing Akt activity or blocking mTOR, reverses the
      pathologic effects associated with excess VEGF signaling in the tumor
      vasculature. However, unexpected findings following mTOR inhibition in vivo
      highlight the seemingly paradoxical and complex effects of rapamycin on various
      cell types within the tumor microenvironment.

PMID- 16904606
TI  - Microcephalin guards against small brains, genetic instability, and cancer.
AB  - Through its roles in cell cycle control and DNA damage response, microcephalin
      (also known as BRIT1 or MCPH1) has been implicated in fundamental biological
      processes, including regulation of brain size and maintenance of genomic
      integrity. Two new reports in Nature Cell Biology and this issue of Cancer Cell
      provide further insights into the functions of microcephalin in DNA damage
      checkpoints and timing of mitosis. Depletion or disease-associated mutations of
      microcephalin resulted in centrosomal abnormalities and chromosomal instability.
      These findings and aberrantly reduced expression in human carcinomas identify
      microcephalin as a candidate novel tumor suppressor.

PMID- 16904607
TI  - Co-opted integrin signaling in ErbB2-induced mammary tumor progression.
AB  - Although almost two decades of study point to a central role for aberrant ErbB2
      activation in breast cancer, many cellular and biochemical mechanisms underlying
      ErbB2-induced tumor initiation and progression remain to be resolved. A study by
      Guo et al. published recently in Cell indicates that the signaling function of
      beta4 integrin actively contributes to the initiation, growth, and invasion of
      ErbB2-induced mammary tumors in transgenic mice by promoting the activation of c
      Jun and STAT3. These observations offer novel mechanistic insight into ErbB2
      action and highlight the notion that ErbB2 co-opts the functions of other
      signaling proteins to elicit tumor progression.

PMID- 16904608
TI  - pVHL's kryptonite: E2-EPF UCP.
AB  - E2-EPF ubiquitin carrier protein (UCP) is a member of an E2 family of enzymes
      that catalyzes the ligation of ubiquitin to proteins targeted for destruction by
      the proteasome. UCP is overexpressed in common human cancers, suggesting its
      involvement in oncogenesis, but a physiologic target of UCP has not been
      identified. In a recent report published in Nature Medicine, Jung et al.
      identified von Hippel-Lindau (VHL) tumor suppressor protein, which targets the
      alpha subunit of hypoxia-inducible factor (HIF) for ubiquitin-mediated
      destruction, as a bona fide substrate of UCP and demonstrated a potential pVHL
      HIF pathway-dependent role for UCP in cancer development.

PMID- 16904609
TI  - Prediction of venous metastases, recurrence, and prognosis in hepatocellular
      carcinoma based on a unique immune response signature of the liver
      microenvironment.
AB  - Hepatocellular carcinoma (HCC) is an aggressive malignancy mainly due to
      metastases or postsurgical recurrence. We postulate that metastases are
      influenced by the liver microenvironment. Here, we show that a unique
      inflammation/immune response-related signature is associated with noncancerous
      hepatic tissues from metastatic HCC patients. This signature is principally
      different from that of the tumor. A global Th1/Th2-like cytokine shift in the
      venous metastasis-associated liver microenvironment coincides with elevated
      expression of macrophage colony-stimulating factor (CSF1). Moreover, a refined 17
      gene signature was validated as a superior predictor of HCC venous metastases in
      an independent cohort, when compared to other clinical prognostic parameters. We
      suggest that a predominant humoral cytokine profile occurs in the metastatic
      liver milieu and that a shift toward anti-inflammatory/immune-suppressive
      responses may promote HCC metastases.

PMID- 16904610
TI  - Bcl-xL gain of function and p19 ARF loss of function cooperate oncogenically with
      Myc in vivo by distinct mechanisms.
AB  - Overexpression of Bcl-xL, loss of p19 ARF, and loss of p53 all accelerate Myc
      oncogenesis. All three lesions are implicated in suppressing Myc-induced
      apoptosis, suggesting that this is a common mechanism by which they synergize
      with Myc. However, using an acutely switchable model of Myc-induced
      tumorigenesis, we demonstrate that each lesion cooperates with Myc in vivo by a
      distinct mechanism. While Bcl-xL blocks Myc-induced apoptosis, inactivation of
      p19 ARF enhances it. However, this increase in apoptosis is matched by increased
      Myc-induced proliferation. p53 inactivation shares features of both lesions,
      partially suppressing apoptosis while augmenting proliferation. Bcl-xL and p19
      ARF loss together synergize to further accelerate Myc oncogenesis. Thus,
      differing lesions cooperate oncogenically with Myc by discrete mechanisms that
      can themselves synergize with each other.

PMID- 16904611
TI  - An Xpd mouse model for the combined xeroderma pigmentosum/Cockayne syndrome
      exhibiting both cancer predisposition and segmental progeria.
AB  - Inborn defects in nucleotide excision DNA repair (NER) can paradoxically result
      in elevated cancer incidence (xeroderma pigmentosum [XP]) or segmental progeria
      without cancer predisposition (Cockayne syndrome [CS] and trichothiodystrophy
      [TTD]). We report generation of a knockin mouse model for the combined disorder
      XPCS with a G602D-encoding mutation in the Xpd helicase gene. XPCS mice are the
      most skin cancer-prone NER model to date, and we postulate an unusual NER
      dysfunction that is likely responsible for this susceptibility. XPCS mice also
      displayed symptoms of segmental progeria, including cachexia and progressive loss
      of germinal epithelium. Like CS fibroblasts, XPCS and TTD fibroblasts from human
      and mouse showed evidence of defective repair of oxidative DNA lesions that may
      underlie these segmental progeroid symptoms.

PMID- 16904612
TI  - The TSC2/mTOR pathway drives endothelial cell transformation induced by the
      Kaposi's sarcoma-associated herpesvirus G protein-coupled receptor.
AB  - The Kaposi's sarcoma-associated herpesvirus (KSHV), the infectious causative
      agent of Kaposi's sarcoma (KS), encodes a G protein-coupled receptor (vGPCR)
      implicated in the initiation of KS. Here we demonstrate that Kaposi's
      sarcomagenesis involves stimulation of tuberin (TSC2) phosphorylation by vGPCR,
      promoting the activation of mTOR through both direct and paracrine mechanisms.
      Pharmacologic inhibition of mTOR with rapamycin prevented vGPCR sarcomagenesis,
      while overactivation of this pathway was sufficient to render endothelial cells
      oncogenic. Moreover, mice haploinsufficient for TSC2 are predisposed to vascular
      sarcomas remarkably similar to KS. Collectively, these results implicate mTOR in
      KS initiation and suggest that the sarcomagenic potential of KSHV may be a direct
      consequence of the profound sensitivity of endothelial cells to vGPCR
      dysregulation of the TSC2/mTOR pathway.

PMID- 16904614
TI  - A call for action.

PMID- 16904615
TI  - Access to hospitals in the wake of terrorism: challenges and needs for
      maintaining public confidence.
AB  - The problem of surge capacity in the wake of a terror-related emergency has lead
      to a number of interesting proposals designed to mitigate the effects of crowds
      as well as deficiencies in patient care capacities. The most controversial of
      these is a proposal to close hospital doors in the wake of a mass casualty terror
      event. However, several specific challenges posed by mass casualty events make
      closing hospitals doors undesirable. These include the need for efficient
      movement of resources, maintenance of social order, and providing the moral
      reassurance needed by the general public in times of crisis. Importantly, these
      challenges are related to features of terrorist events that distinguish such
      events from circumstances of "normal" surge that might result in, for example,
      closure of emergency rooms.

PMID- 16904613
TI  - Pathological angiogenesis is induced by sustained Akt signaling and inhibited by
      rapamycin.
AB  - Endothelial cells in growing tumors express activated Akt, which when modeled by
      transgenic endothelial expression of myrAkt1 was sufficient to recapitulate the
      abnormal structural and functional features of tumor blood vessels in nontumor
      tissues. Sustained endothelial Akt activation caused increased blood vessel size
      and generalized edema from chronic vascular permeability, while acute
      permeability in response to VEGF-A was unaffected. These changes were reversible,
      demonstrating an ongoing requirement for Akt signaling for the maintenance of
      these phenotypes. Furthermore, rapamycin inhibited endothelial Akt signaling,
      vascular changes from myrAkt1, tumor growth, and tumor vascular permeability. Akt
      signaling in the tumor vascular stroma was sensitive to rapamycin, suggesting
      that rapamycin may affect tumor growth in part by acting as a vascular Akt
      inhibitor.

PMID- 16904616
TI  - Integrating disaster preparedness into a community health nursing course: one
      school's experience.
AB  - It is not practical to wait for a disaster, whether natural or human-made, to
      learn how to respond and provide specialized care. The Long Island University
      School of Nursing in Brooklyn, New York, has developed a specific educational
      experience for undergraduate nursing students enrolled in community health. The
      course is offered in the senior semester and includes didactic material based on
      the International Nursing Coalition for Mass Casualty Education-recommended
      competencies. Students are given the opportunity to apply the learning and
      develop additional skills by participating in a mock drill. Although anecdotal
      comments from the students indicate that the coursework has been helpful,
      additional research is planned to evaluate the program.

PMID- 16904617
TI  - Disaster preparedness at the University of Pittsburgh School of Nursing: four
      years of progress.

PMID- 16904618
TI  - Realities of disaster preparedness in rural hospitals.
AB  - Disaster preparedness has always been an area of major concern for the medical
      community, but recent world events have prompted an increased interest. The
      health care system must respond to disasters of all types, whether the incidents
      occur in urban or rural settings. Although the barriers and challenges are
      different in the rural setting, common areas of preparedness must be explored.
      This study examines the experiences of rural hospital emergency departments with
      threat preparedness. Data were gathered through a nationwide survey to describe
      emergency department experience with specific incidents, as well as the frequency
      of occurrence of these events. Expanding surge capacity of hospitals and
      developing a community-wide response to natural or human-made incidents is
      crucial in mitigating long-term effects on the health care system. Analysis of
      preparedness activities will help identify common themes to better prioritize
      preparedness activities and maximize a hospital's response capabilities.

PMID- 16904619
TI  - Social and mental health needs assessment of Katrina evacuees.
AB  - Hurricane Katrina made landfall along the Gulf Coast as a Category 3 storm on
      August 29, 2005. Many residents were evacuated to neighboring cities owing to
      massive destruction. Working with the City of Houston Health Department,
      researchers conducted a medical and psychological needs assessment of 124
      Hurricane Katrina evacuees in Houston shelters from September 4-12, 2005. Among
      those willing to talk about their experiences, 41% were afraid they would die,
      16% saw someone close to them injured or die, 17% saw violence, and 6% directly
      experienced physical violence. When using a version of the Impact of Stress
      Experiences scale, the majority of evacuees scored as experiencing moderate
      (38.6%) to severe (23.9%) post-traumatic stress disorder (PTSD) symptoms. These
      data suggest that in addition to challenges in finding loved ones, housing, and
      jobs, many Katrina survivors have experienced significant psychological trauma
      that may lead to future PTSD.

PMID- 16904620
TI  - Con-fusing contours & pieces of glass.
AB  - We present a new illusory display in which illusory contours are misaligned with
      physical contours. In these displays, illusory Kanizsa squares, induced by the so
      called pacmen, are positioned on top of a background grid of bars. The
      misalignment of the illusory contours with respect to physical contours of the
      grid of bars induces an overall 'restless' appearance and evokes the impression
      that parts of the grid within the illusory square are shifted. To test this
      impression, we created stimuli in which illusory squares were superimposed on a
      grid at different positions, where the grid could consist of either straight bars
      or indented bars. After briefly flashing these stimuli, observers reported
      indentations of the background grid for those cases in which physical and
      illusory contours were misaligned. In a control condition, the pacmen were
      replaced by crosses (not inducing an illusory square) at the same positions; as
      expected much less illusory shifts were reported in this condition. In a second
      experiment, we further tested the direction of the perceived shifts, revealing
      similar trends as in the first experiment and a consistent result with respect to
      the reported direction of the shifts. We explore and discuss possible underlying
      mechanisms with regard to our illusory display.

PMID- 16904621
TI  - Temporal reproduction: further evidence for two processes.
AB  - Some authors have suggested separate mechanisms for the processing of temporal
      intervals above versus below 2-3s. Given that the evidence is mixed, the present
      experiment was carried out as a critical test of the separate-mechanism
      hypothesis. Subjects reproduced five standard durations of 1-5s presented in the
      auditory and visual modalities. The Corsi-block test was used to assess effects
      of working-memory span on different interval lengths. Greater working-memory span
      was associated with longer reproductions of intervals of 3-5s. A factor analysis
      run on mean reproduced intervals revealed one modality-unspecific factor for
      durations of 1-2s and two modality-specific factors for longer intervals. These
      results are interpreted as further indications that two different processes
      underlie temporal reproductions of shorter and longer intervals.

PMID- 16904622
TI  - Thermodynamic and kinetic aspects of fat crystallization.
AB  - Naturally occurring fats are multi-component mixtures of triacylglycerols (TAGs),
      which are triesters of fatty acids with glycerol, and of which there are many
      chemically distinct compounds. Due to the importance of fats to the food and
      consumer products industries, fat crystallization has been studied for many years
      and many intricate features of TAG interactions, complicated by polymorphism,
      have been identified. The melting and crystallization properties of
      triacylglycerols are very sensitive to even small differences in fatty acid
      composition and position within the TAG molecule which cause steric hindrance.
      Differences of fatty acid chain length within a TAG lead to packing
      imperfections, and differences in chain lengths between different TAG molecules
      lead to a loss of intersolubility in the solid phase. The degree of saturation is
      hugely important as the presence of a double bond in a fatty acid chain causes
      rigid kinks in the fatty acid chains that produce huge disruption to packing
      structures with the result that TAGs containing double bonds have much lower
      melting points than completely saturated TAGs. All of these effects are more
      pronounced in the most stable polymorphic forms, which require the most efficient
      molecular packing. The crystallization of fats is complicated not just by
      polymorphism, but also because it usually occurs from a multi-component melt
      rather than from a solvent which is more common in other industrial
      crystallizations. This renders the conventional treatment of crystallization as a
      result of supersaturation somewhat meaningless. Most studies in the literature
      consequently quantify crystallization driving forces using the concept of
      supercooling below a distinct melting point. However whilst this is theoretically
      valid for a single component system, it can only at best represent a rough
      approximation for natural fat systems, which display a range of melting points.
      This paper reviews the latest attempts to describe the sometimes complex phase
      equilibria of fats using fundamental relationships for chemical potential that
      have so far been applied to individual species in melts of unary, binary and
      ternary systems. These can then be used to provide a framework for quantifying
      the true crystallization driving forces of individual components within a multi
      component melt. These are directly related to nucleation and growth rates, and
      are also important in the prediction of polymorphic occurrence, crystal
      morphology and surface roughness. The methods currently used to evaluate
      induction time, nucleation rate and overall crystallization rate data are also
      briefly described. However, mechanistic explanations for much of the observed
      crystallization behaviour of TAG mixtures remain unresolved.

PMID- 16904623
TI  - Resveratrol increases glutamate uptake and glutamine synthetase activity in C6
      glioma cells.
AB  - Resveratrol, a phytoalexin found mainly in grapes, is a promising natural product
      with anti-cancer and cardio-protective activities. Here, we investigated, in C6
      glioma cells, the effect of resveratrol on some specific parameters of astrocyte
      activity (glutamate uptake, glutamine synthetase and secretion of S100B, a
      neurotrophic cytokine) commonly associated with the protective role of these
      cells. Cell proliferation was significantly decreased by 8% and 26%, following
      24h of treatment with 100 and 250 microM resveratrol. Extracellular S100B
      increased after 48 h of resveratrol exposure. Short-term resveratrol exposure
      (from 1 to 100 microM) induced a linear increase in glutamate uptake (up to 50%
      at 100 microM resveratrol) and in glutamine synthetase activity. Changes in these
      glial activities can contribute to the protective role of astrocytes in brain
      injury conditions, reinforcing the putative use of this compound in the
      therapeutic arsenal against neurodegenerative diseases and ischemic disorders.

PMID- 16904624
TI  - Kinetic study of the plastoquinone pool availability correlated with H2O2 release
      in seawater and antioxidant responses in the red alga Kappaphycus alvarezii
      exposed to single or combined high light, chilling and chemical stresses.
AB  - Under biotic/abiotic stresses, the red alga Kappaphycus alvarezii reportedly
      releases massive amounts of H(2)O(2) into the surrounding seawater. As an
      essential redox signal, the role of chloroplast-originated H(2)O(2) in the
      orchestration of overall antioxidant responses in algal species has thus been
      questioned. This work purported to study the kinetic decay profiles of the redox
      sensitive plastoquinone pool correlated to H(2)O(2) release in seawater,
      parameters of oxidative lesions and antioxidant enzyme activities in the red alga
      Kappaphycus alvarezii under the single or combined effects of high light, low
      temperature, and sub-lethal doses of 3-(3,4-dichlorophenyl)-1,1-dimethylurea
      (DCMU) and 2,5-dibromo-3-methyl-6-isopropyl-p-benzoquinone (DBMIB), which are
      inhibitors of the thylakoid electron transport system. Within 24 h, high light
      and chilling stresses distinctly affected the availability of the PQ pool for
      photosynthesis, following Gaussian and exponential kinetic profiles,
      respectively, whereas combined stimuli were mostly reflected in exponential
      decays. No significant correlation was found in a comparison of the PQ pool
      levels after 24 h with either catalase (CAT) or ascorbate peroxidase (APX)
      activities, although the H(2)O(2) concentration in seawater (R=0.673), total
      superoxide dismutase activity (R=0.689), and particularly indexes of protein
      (R=0.869) and lipid oxidation (R=0.864), were moderately correlated. These data
      suggest that the release of H(2)O(2) from plastids into seawater possibly
      impaired efficient and immediate responses of pivotal H(2)O(2)-scavenging
      activities of CAT and APX in the red alga K. alvarezii, culminating in short-term
      exacerbated levels of protein and lipid oxidation. These facts provided a
      molecular basis for the recognized limited resistance of the red alga K.
      alvarezii under unfavorable conditions, especially under chilling stress.

PMID- 16904626
TI  - Proton pumping mechanism of bovine heart cytochrome c oxidase.
AB  - X-ray structures of bovine heart cytochrome c oxidase at 1.8/1.9 A resolution in
      the oxidized/reduced states exhibit a redox coupled conformational change of an
      aspartate located near the intermembrane surface of the enzyme. The alteration of
      the microenvironment of the carboxyl group of this aspartate residue indicates
      the occurrence of deprotonation upon reduction of the enzyme. The residue is
      connected with the matrix surface of the enzyme by a hydrogen-bond network that
      includes heme a via its propionate and formyl groups. These X-ray structures
      provide evidence that proton pumping occurs through the hydrogen bond network and
      is driven by the low spin heme. The function of the aspartate is confirmed by
      mutation of the aspartate to asparagine. Although the amino acid residues of the
      hydrogen bond network and the structures of the low spin heme peripheral groups
      are not completely conserved amongst members of the heme-copper terminal oxidase
      superfamily, the existence of low spin heme and the hydrogen bond network
      suggests that the low spin heme provides the driving element of the proton
      pumping process.

PMID- 16904627
TI  - Comparison of excitation and emission ratiometric fluorescence methods for
      quantifying the membrane dipole potential.
AB  - We are interested in developing fluorescence methods for quantifying lateral
      variations in the dipole potential across cell surfaces. Previous work in this
      laboratory showed that the ratio of fluorescence intensities of the voltage
      sensitive dye di-8-ANEPPS using excitation wavelengths at 420 and 520 nm
      correlates well with measurements of the dipole potential. In the present work we
      evaluate the use of di-8-ANEPPS and an emission ratiometric method for measuring
      dipole potentials, as Bullen and Saggau (Biophys. J. 65 (1999) 2272-2287) have
      done to follow changes in the membrane potential in the presence of an externally
      applied field. Emission ratiometric methods have distinct advantages over
      excitation methods when applied to fluorescence microscopy because only a single
      wavelength is needed for excitation. We found that unlike the excitation ratio,
      the emission ratio does not correlate with the dipole potential of vesicles made
      from different lipids. A difference in the behaviour of the emission ratio in
      saturated compared to unsaturated lipid vesicles was noted. Furthermore, the
      emission ratio did not respond in the same way as the excitation ratio when
      cholesterol, 6-ketocholestanol, 7-ketocholesterol, and phloretin were added to
      dimyristoylphosphatidylcholine (DMPC) vesicles. We attribute the lack of
      correlation between the emission ratio and the dipole potential to simultaneous
      changes in membrane fluidity caused by changes in membrane composition, which do
      not occur when the electric field is externally applied as in the work of Bullen
      and Saggau. Di-8-ANEPPS can, thus, only be used via an excitation ratiometric
      method to quantify the dipole potential.

PMID- 16904628
TI  - Sphingolipid players in the leukemia arena.
AB  - Sphingolipids function as bioactive mediators of different cellular processes,
      mostly proliferation, survival, differentiation and apoptosis, besides being
      structural components of cellular membranes. Involvement of sphingolipid
      metabolism in cancerogenesis was demonstrated in solid tumors as well as in
      hematological malignancies. Herein, we describe the main biological and clinical
      aspects of leukemias and summarize data regarding sphingolipids as mediators of
      apoptosis triggered in response to anti-leukemic agents and synthetic analogs as
      inducers of cell death as well. We also report the contribution of molecules that
      modulate sphingolipid metabolism to development of encouraging strategies for
      leukemia treatment. Finally we address how deregulation of sphingolipid
      metabolism is associated to occurrence of therapy resistance both in vitro and in
      vivo. Sphingolipids can be considered promising therapeutic tools alone or in
      combination with other compounds, as well as valid targets in the attempt to
      eradicate leukemia and overcome drug resistance.

PMID- 16904629
TI  - In-vitro analysis of normal and aneurismal human ascending aortic tissues using
      FT-IR microspectroscopy.
AB  - FTIR microspectroscopy has shown to be a proven tool in the investigation of many
      tissue types. We have used this spectroscopic approach to analyse structural
      differences between normal and aneurismal aortic tissues and also aortas from
      patients with congenital anomalies like aortic bicuspid valves. Spectral analysis
      showed important variations in amide I and II regions, related to changes in
      alpha-helix and beta-sheet secondary structure of proteins that seem to be
      correlated to structural modifications of collagen and elastin. These proteins
      are the major constituents of the aortic wall associated to smooth muscular
      cells. The amide regions have thus been identified as a marker of structural
      modifications related to these proteins whose modifications can be associated to
      a given aortic pathological situation. Both univariate (total absorbance image
      and band ratio) and multivariate (principal components analysis) analyses of the
      spectral information contained in the infrared images have been performed.
      Differences between tissues have been identified by these two approaches and
      allowed to separate each group of aortic tissues. However, with univariate band
      ratio analysis, the pathological group was found to be composed of samples from
      aneurismal aortas associated or not with an aortic bicuspid valve. In contrast,
      PCA was able to separate these two types of aortic pathologies. For other groups,
      PCA and band ratio analysis can differentiate between normal, aneurismal, and
      none dilated aortas from patients with a bicuspid aortic valve.

PMID- 16904630
TI  - Classifier ensembles for protein structural class prediction with varying
      homology.
AB  - Structural class characterizes the overall folding type of a protein or its
      domain. A number of computational methods have been proposed to predict
      structural class based on primary sequences; however, the accuracy of these
      methods is strongly affected by sequence homology. This paper proposes, an
      ensemble classification method and a compact feature-based sequence
      representation. This method improves prediction accuracy for the four main
      structural classes compared to competing methods, and provides highly accurate
      predictions for sequences of widely varying homologies. The experimental
      evaluation of the proposed method shows superior results across sequences that
      are characterized by entire homology spectrum, ranging from 25% to 90% homology.
      The error rates were reduced by over 20% when compared with using individual
      prediction methods and most commonly used composition vector representation of
      protein sequences. Comparisons with competing methods on three large benchmark
      datasets consistently show the superiority of the proposed method.

PMID- 16904631
TI  - Subcellular localization of phosphatidylinositol synthesis.
AB  - It is well-established that the endoplasmic reticulum is the major site of
      phosphatidylinositol (PtdIns) synthesis. The PtdIns synthetic ability of other
      organelles, such as plasma membrane and nucleus, remains controversial. In the
      present study, we re-examine this question by comparing PtdIns synthesis in
      isolated cytoplasts (enucleated cells) with that in corresponding karyoplasts
      (nuclei surrounded by plasma membrane but lacking most cytoplasmic components).
      We report that cytoplasts are competent to carry out both basal and stimulated
      PtdIns synthesis as well as polyphosphoinositide hydrolysis, while karyoplasts
      can neither synthesize PtdIns nor hydrolyze phosphoinositides in response to
      agonists. The karyoplasts are, however, capable of synthesizing
      phosphatidylcholine (PtdCho), as previously reported. From these data, we
      conclude that PtdIns synthesis is limited to cytoplasmic components, and cannot
      be sustained by either plasma membrane or nucleus under conditions that permit
      robust PtdCho synthesis.

PMID- 16904632
TI  - Excess magnesium inhibits excess calcium-induced matrix-mineralization and
      production of matrix gla protein (MGP) by ATDC5 cells.
AB  - We found that excessive extracellular Ca2+ and/or Mg2+ affected the process of
      matrix mineralization and glycosaminoglycan (GAG) production by cells of the
      prechondrogenic cell line, ATDC5. Excess Ca2+ induced both matrix mineralization
      and GAG production in the cells. On the other hand, excess Mg2+ reduced this Ca2+
      mediated rise in both mineralization and GAG production in them. Next we measured
      the mRNA levels of cartilage-associated genes such as calcium-sensing receptor
      (CaSR), matrix gla protein (MGP), bone gla protein (BGP), and Runt-related
      transcription factor 2 (Runx2) in ATDC5 cells. Excess Ca2+ increased the MGP,
      BGP, and CaSR mRNA levels, and excess Mg2+ reduced the Ca2+-induced increase in
      the MGP mRNA level in the cells. The changes in the MGP mRNA level paralleled
      those in the MGP protein level. These data show that Ca2+ and Mg2+ regulated the
      matrix mineralization positively and negatively, respectively, in ATDC5 cells and
      suggest that excess Mg2+ might inhibit the excess Ca2+-promoted mineralization
      mediated by MGP induction in chondrocytes.

PMID- 16904633
TI  - Density and sub-cellular distribution of cardiac and neuronal sodium channel
      isoforms in rat ventricular myocytes.
AB  - In cardiac ventricular myocytes, Na current is generated mainly by the cardiac
      NaV1.5 isoform, but the presence of "neuronal" Na channel isoforms in the heart
      has been demonstrated recently. In this study, we quantified the density and sub
      cellular distribution of cardiac and neuronal channel isoforms in rat ventricular
      myocytes. INa was recorded using the patch clamp technique in control and
      detubulated myocytes. Detubulation reduced cell capacitance (by approximately
      29%) but maximum conductance was not altered (1.94+/-0.15, 14 control vs 1.98+/
      0.19 nS/pF, 17 detubulated myocytes). The kinetic properties of INa were similar
      in both cell types suggesting good voltage control of surface and t-tubule
      membranes. We calculated Na channel densities assuming the sub-cellular current
      localization we recently provided (neuronal isoform: approximately 11% of total
      sarcolemmal current, approximately 3% of cell surface, and approximately 31% of t
      tubule current). Single channel conductances were assumed to be 2.2 and 2.5 pS
      for the cardiac and neuronal isoforms, respectively, after accounting for the use
      of low Na concentration. We calculated that the density of the cardiac Na channel
      isoform is relatively constant (in channels/microm2: approximately 11 in total
      sarcolemma, approximately 13 at the cell surface, approximately 10 at the t
      tubules). In contrast, neuronal Na channel isoforms are concentrated at the t
      tubules (in channels/microm2: approximately 1 in total sarcolemma, approximately
      0.3 at the cell surface, approximately 2.5 at the t-tubules). We conclude that,
      in contrast to skeletal muscle in which Na channel density is higher at the cell
      surface than the t-tubules, in ventricular cardiac myocytes the sub-cellular
      distribution of Na channel density is relatively homogeneous (approximately 13
      channels/microm2).

PMID- 16904634
TI  - Histone deacetylase inhibitor trichostatin A and proteasome inhibitor PS-341
      synergistically induce apoptosis in pancreatic cancer cells.
AB  - Pancreatic cancer is a common and lethal malignancy. Pancreatic cancer cells
      overexpress multiple anti-apoptotic factors and death receptor decoys, and are
      strongly resistant to radiation and to 5-fluorouracil (5-FU)- or gemcitabine
      (Gem)-based chemotherapy regimens. We have found that low-dose proteasome
      inhibitor PS-341 and histone deacetylase inhibitor trichostatin A (TSA)
      synergistically induce cytotoxicity in a panel of eight diverse pancreatic cancer
      cell lines. Combining TSA with PS-341 effectively inactivated NFkappaB signaling,
      downregulated the predominant endogenous anti-apoptotic factor Bcl-XL
      overexpression, and disrupted MAP kinase pathway. The combined drug regimen
      effectively inflicted an average of 71.5% apoptotic cell death (55.2-80%) in
      diverse pancreatic cancer cell lines by activating the intrinsic apoptotic
      pathway. CONCLUSION: The TSA/PS-341 regimen may represent a potential novel
      therapeutic strategy for pancreatic cancer.

PMID- 16904635
TI  - Cell based screening of inhibitors of transthyretin aggregation.
AB  - The amyloidoses are the extracellular subset of a group of diseases in which in
      vivo protein misfolding leads to a pathologic gain of function, i.e., aggregation
      leading to protein deposition, with subsequent tissue damage. Wild-type and
      mutant transthyretins (TTR) are the etiologic agents in prototypic systemic
      amyloidoses. We describe a cell-based assay that measures the cytotoxicity of
      physiologic concentrations of the amyloidogenic Val30Met TTR variant (V30M TTR)
      using cells of the same lineage as the in vivo tissue target of amyloid
      deposition. We have utilized the assay to screen small molecules for their
      capacity to inhibit the TTR-induced cell damage. We compared the inhibitory
      activity of each compound with its ability to prevent TTR fibril formation in
      vitro. Our results emphasize the importance of screening compounds under
      physiologic conditions. Moreover, if a common conformational intermediate is
      responsible for cell death in all the amyloid diseases, the cell-based assay has
      the potential to aid in the discovery of compounds useful in the treatment of
      amyloidoses caused by other misfolded proteins as well as those caused by TTR.

PMID- 16904636
TI  - A novel Kruppel related factor consisting of only a KRAB domain is expressed in
      the murine trigeminal ganglion.
AB  - The largest family of zinc-finger (ZnF) transcription factors is that containing
      the Kruppel-associated box, or KRAB domain. The amino-terminal KRAB domain of
      these proteins functions as a transcriptional repressor with the downstream ZnF
      motifs providing DNA-binding specificity. Here we report the identification and
      characterization of a novel murine Kruppel-related factor (KLF), MIF1, which
      contains a KRAB domain but lacks a ZnF motif. Western blot analysis identified
      MIF1-like proteins in the murine trigeminal ganglion (TG) and immunostaining
      localized these proteins primarily to the cytoplasm of TG neuronal cell bodies.
      In situ hybridization for Mif1 transcripts confirms the selective expression of
      Mif1 in TG neurons. Consistent with the non-nuclear localization of MIF1 we could
      detect no transcriptional repressor activity of the MIF1 protein. However MIF1
      appears to be capable of interacting with the co-repressor TIF1beta and exhibits
      transcription repressor activity when fused to yeast GAL4 binding domain protein.
      Genomic analysis of Mif1 sequence suggests that the Mif1 transcript may result
      from splicing of a longer KRAB-ZnF containing transcript.

PMID- 16904638
TI  - Characteristics of bone marrow-derived endothelial progenitor cells in aged mice.
AB  - Evidence for dysfunction of endothelial repair in aged mice was sought by
      studying the pattern of induced differentiation, quantity, and function of bone
      marrow-derived endothelial progenitor cells (EPCs) in aged mice. The CD117
      positive stem cell population was separated from bone marrow by magnetic
      activated cell-sorting system (MACS), and EPCs were defined by demonstrating the
      expression of CD117+CD34+Flk-1+ by flow cytometry. After 7 days of culture, the
      number of clones formed was counted, and proliferation and migration of EPCs were
      analyzed by MTT[3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide]
      assay and modified Boyden chamber assay. The results demonstrated that compared
      to the control group, the quantity of bone marrow-derived CD117+ stem cells and
      EPCs, as well as the proliferation, migration, the number of clones formed, and
      phagocytotic function of EPCs were significantly reduced in aged mice. There were
      no significant differences in the morphology and induced differentiation pattern
      of EPCs between the aged mouse group and the control group. Authors suggest that
      the dysfunction of EPCs may serve as a surrogate parameter of vascular function
      in old mice.

PMID- 16904637
TI  - Location of intrinsic and inducible phenoloxidase activity in molluscan
      hemocyanin.
AB  - The phenoloxidase (PO) activity of the hemocyanins (Hcs) from two molluscan
      species, the gastropod Helix pomatia (Hp) and the cephalopod Sepia officinalis
      (So), was studied. With catechol as substrate the Hcs showed a weak o-diPO
      activity, which was moderately enhanced on limited proteolysis with subtilisin.
      The sites in the Hc molecules mainly responsible for this activity were
      identified. The highest intrinsic o-diPO activity and also by far the highest
      level of induction were found in the functional units (FUs) Hp f and So g,
      isolated from Hp beta-Hc and So Hc (subunit 2), respectively. The results thus
      support the earlier conclusion, made on the basis of sequence homology between
      molluscan Hcs, that Hp f and So g are functional and structural analogues. The
      subtilisin treatment of Hp f also induced monoPO activity, considered to be at
      the origin of browning of the sample.

PMID- 16904639
TI  - Increased ATP-sensitive K+ channel expression during acute glucose deprivation.
AB  - ATP-sensitive potassium (KATP) channels play a central role in glucose-stimulated
      insulin secretion (GSIS) by pancreatic beta-cells. Activity of these channels is
      determined by their open probability (Po) and the number of channels present in a
      cell. Glucose is known to reduce Po, but whether it also affects the channel
      density is unknown. Using INS-1 model beta-cell line, we show that the expression
      of K(ATP) channel subunits, Kir6.2 and SUR1, is high at low glucose, but declines
      sharply when the ambient glucose concentration exceeds 5mM. In response to
      glucose deprivation, channel synthesis increases rapidly by up-regulating
      translation of existing mRNAs. The effects of glucose deprivation could be
      mimicked by pharmacological activation of 5'-AMP-activated protein kinase with 5
      aminoimidazole-4-carboxamide ribonucleotide and metformin. Pancreatic beta-cells
      which have lost their ability for GSIS do not show such changes implicating a
      possible (patho-)physiological link between glucose-regulated KATP channel
      expression and the capacity for normal GSIS.

PMID- 16904640
TI  - Targeted optical imaging of cancer cells using lectin-binding BODIPY conjugated
      avidin.
AB  - Lectins (asialo-receptor family) are expressed on a number of tumors that develop
      peritoneal metastases. To demonstrate that fluorescence imaging based on lectin
      binding is applicable for a variety of tumors, we conjugated BODIPY to avidin
      (avidin-BODIPY), and studied the efficacy of tumor targeting in 9 cancer cell
      lines in vitro and an ovarian cancer cell line in vivo using a murine peritoneal
      cancer model. All 9 cell lines showed specific intracellular accumulation with
      avidin-BODIPY on fluorescence microscopy and flow cytometry. In vivo spectral
      molecular imaging clearly visualized the peritoneal tumor foci with avidin
      BODIPY, whereas, deglycosylated avidin-BODIPY (neutravidin-BODIPY) showed only
      minimal fluorescence from the tumor foci and was accompanied by higher background
      signals. These results suggest the lectin-targeted molecular imaging technique
      using a targeted green fluorescence probe is potentially useful in a wide variety
      of cancers with a proclivity for dissemination in the peritoneal space.

PMID- 16904641
TI  - Heparin localization and fine structure regulate Burkitt's lymphoma growth.
AB  - Burkitt's lymphoma (BL) is a B-cell malignancy associated with the Epstein-Barr
      virus (EBV). Mounting evidence has implicated heparan sulfate proteoglycans and
      heparan sulfate-like glycosaminoglycans (HSGAGs) in the initiation, severity, and
      progression of the malignancy. The importance of HSGAGs in regulating BL cell
      growth was therefore examined. Extracellular exogenous heparin inhibited cell
      growth >30%, while heparin internalized with poly(beta-amino ester)s promoted
      proliferation up to 58%. The growth-modulating effects of heparin and
      internalized heparin were dependent on cell surface HSGAGs, PI3K, and Erk/Mek.
      Treatment of cells with protamine sulfate or with heparinases potently inhibited
      proliferation, with the greatest effects induced by heparinase I. Cell surface
      HSGAGs therefore play an important role in regulating BL proliferation and may
      offer a potential target for therapeutic intervention.

PMID- 16904642
TI  - Cell-based chemical genetic screen identifies damnacanthal as an inhibitor of HIV
      1 Vpr induced cell death.
AB  - Viral protein R (Vpr), one of the human immunodeficiency virus type 1 (HIV-1)
      accessory proteins, contributes to multiple cytopathic effects, G2 cell cycle
      arrest and apoptosis. The mechanisms of Vpr have been intensely studied because
      it is believed that they underlie HIV-1 pathogenesis. We here report a cell-based
      small molecule screen on Vpr induced cell death in the context of HIV-1
      infection. From the screen of 504 bioactive compounds, we identified damnacanthal
      (Dam), a component of noni [corrected] as an inhibitor of Vpr induced cell death.
      Our studies illustrate a novel efficient platform for drug discovery and
      development in anti-HIV therapy which should also be applicable to other viruses.

PMID- 16904643
TI  - The N-terminal domain of CCL21 reconstitutes high affinity binding, G protein
      activation, and chemotactic activity, to the C-terminal domain of CCL19.
AB  - CC chemokine receptor 7 (CCR7), which regulates the trafficking of leucocytes to
      the secondary lymphoid organs, has two endogenous chemokine ligands: CCL19 and
      CCL21. Although both ligands possess similar affinities for the receptor and
      similar abilities to promote G protein activation and chemotaxis, they share only
      25% sequence identity. Here, we show that substituting N-terminal six amino acids
      of CCL21 (SDGGAQ) for the corresponding N-terminal domain of CCL19 (GTNDAE)
      results in a chimeric chemokine that exhibits high affinity binding and G protein
      activation of CCR7. These data demonstrate that despite dissimilar sequences, the
      amino terminal hexapeptide of these two chemokines is capable of performing
      similar roles resulting in receptor activation.

PMID- 16904644
TI  - SUMO down-regulates the activity of Elf4/myeloid Elf-1-like factor.
AB  - Myeloid elf-1-like factor (MEF) or Elf4 is an ETS protein known to regulate the
      basal expression of the anti-microbial peptides, lysozyme and human beta-defensin
      2, in epithelial cells and activate the transcription of perforin in natural
      killer cells. The numerous target genes of MEF and its biological functions
      signify the importance of this Ets transcription factor. Here we show that MEF is
      modified by conjugation with SUMO-1/-2 (small ubiquitin-related modifier) both in
      mammalian cells and in Escherichia coli overexpressing human SUMO-1/-2. We
      identified by point mutation that lysine 657 of MEF is the site for sumoylation.
      This modification down-regulated MEF activity on lysozyme and perforin promoters,
      and decreased the lysozyme mRNA expression. Chromatin immuno-precipitation
      analysis revealed that SUMO-conjugation diminished the recruitment of MEF to the
      lysozyme promoter, which partly explains the down-regulation of MEF activity by
      SUMO. These findings contribute to our understanding of the regulation of the ETS
      factor MEF.

PMID- 16904645
TI  - Increased efficacy of HIV-1 neutralization by antibodies at low CCR5 surface
      concentration.
AB  - It has been observed that some antibodies, including the CD4-induced (CD4i)
      antibody IgG X5 and the gp41-specific antibody IgG 2F5, exhibit higher
      neutralizing activity in PBMC-based assays than in cell line based assays [J.M.
      Binley, T. Wrin, B. Korber, M.B. Zwick, M. Wang, C. Chappey, G. Stiegler, R.
      Kunert, S. Zolla-Pazner, H. Katinger, C.J. Petropoulos, D.R. Burton,
      Comprehensive cross-clade neutralization analysis of a panel of anti-human
      immunodeficiency virus type 1 monoclonal antibodies, J. Virol. 78 (2004) 13232
      13252]. It has been hypothesized that the lower CCR5 concentration on the surface
      of the CD4 T lymphocytes compared to that on cell lines used for the
      neutralization assays could be a contributing factor to the observed differences
      in neutralizing activity. To test this hypothesis and to further elucidate the
      contribution of CCR5 concentration differences on antibody neutralizing activity,
      we used a panel of HeLa cell lines with well-defined and differential surface
      concentrations of CCR5 and CD4 in a pseudovirus-based assay. We observed that the
      CCR5 cell surface concentration but not the CD4 concentration had a significant
      effect on the inhibitory activity of X5 and several other CD4i antibodies
      including 17b and m9, as well as that of the gp41-specifc antibodies 2F5 and 4E10
      but not on that of the CD4 binding site antibody (CD4bs), b12. The 50% inhibitory
      concentration (IC50) decreased up to two orders of magnitude in cell lines with
      low CCR5 concentration corresponding to that in CD4 T cells used in PBMC-based
      assays (about 10(3) per cell) compared to cell lines with high CCR5 concentration
      (about 10(4) or more). Our results suggest that the CCR5 cell surface
      concentration could be a contributing factor to the high neutralizing activities
      of some antibodies in PBMC-based-assays but other factors could also play an
      important role. These findings could have implications for development of vaccine
      immunogens based on the epitopes of X5 and other CD4i antibodies, for elucidation
      of the mechanisms of HIV-1 neutralization by antibodies, and for design of novel
      therapeutic approaches.

PMID- 16904646
TI  - The Na+/H+ antiporter of the thermohalophilic bacterium Rhodothermus marinus.
AB  - In the thermohalophilic bacterium Rhodothermus marinus, the NADH:quinone
      oxidoreductase (complex I) is encoded by two single genes and two operons, one of
      which contains the genes for five complex I subunits, nqo10-nqo14, a pterin
      carbinolamine dehydratase, and a putative single subunit Na+/H+ antiporter. Here
      we report that the latter encodes indeed a functional Na+/H+ antiporter, which is
      able to confer resistance to Na+, but not to Li+ to an Escherichia coli strain
      defective in Na+/H+ antiporters. In addition, an extensive amino acid sequence
      comparison with several single subunit Na+/H+ antiporters from different groups,
      namely NhaA, NhaB, NhaC, and NhaD, suggests that this might be the first member
      of a new type of Na+/H+ antiporters, which we propose to call NhaE.

PMID- 16904647
TI  - Water-soluble quantum dots for biomedical applications.
AB  - Semiconductor nanocrystals are 1-10nm inorganic particles with unique size
      dependent optical and electrical properties due to quantum confinement (so they
      are also called quantum dots). Quantum dots are new types of fluorescent
      materials for biological labeling with high quantum efficiency, long-term
      photostability, narrow emission, and continuous absorption spectra. Here, we
      discuss the recent development in making water-soluble quantum dots and related
      cytotoxicity for biomedical applications.

PMID- 16904648
TI  - Arsenic trioxide induces gallbladder carcinoma cell apoptosis via downregulation
      of Bcl-2.
AB  - Gallbladder carcinoma (GBC), an aggressive and mostly lethal malignancy, is known
      to be resistant to a number of apoptotic stimuli. Here, we report for the first
      time the pro-apoptosis role of arsenic trioxide (As2O3) in gallbladder carcinoma
      and identify the contribution of Bcl-2 in the As2O3-induced apoptosis. The
      treatment of As2O3 in gallbladder carcinoma cells could induce apoptosis in a
      dose-dependent manner and downregulate the expression of anti-apoptotic protein
      Bcl-2 at mRNA level. Moreover, Bcl-2 overexpression could protect gallbladder
      carcinoma cells from As2O3-induced apoptosis, indicating the contribution of Bcl
      2 in As2O3-induced apoptosis. Taken together, these results suggest that arsenic
      trioxide induces gallbladder carcinoma cell apoptosis via downregulation of Bcl
      2, which may have important therapeutic implications in gallbladder carcinoma
      patients.

PMID- 16904649
TI  - Structural characterization of mumps virus fusion protein core.
AB  - The fusion proteins of enveloped viruses mediating the fusion between the viral
      and cellular membranes comprise two discontinuous heptad repeat (HR) domains
      located at the ectodomain of the enveloped glycoproteins. The crystal structure
      of the fusion protein core of Mumps virus (MuV) was determined at 2.2 A
      resolution. The complex is a six-helix bundle in which three HR1 peptides form a
      central highly hydrophobic coiled-coil and three HR2 peptides pack against the
      hydrophobic grooves on the surface of central coiled-coil in an oblique
      antiparallel manner. Fusion core of MuV, like those of simian virus 5 and human
      respiratory syncytium virus, forms typical 3-4-4-4-3 spacing. The similar
      characterization in HR1 regions, as well as the existence of O-X-O motif in
      extended regions of HR2 helix, suggests a basic rule for the formation of the
      fusion core of viral fusion proteins.

PMID- 16904650
TI  - Regulation of the hypertonic stress response and other cellular functions by the
      Rel-like transcription factor NFAT5.
AB  - Stress, be it from environmental factors or intrinsic to the cell as result of
      growth and metabolism, can be harmful to cells. Mammalian cells have developed
      numerous mechanisms to respond to diverse forms of stress. These mechanisms
      combine signaling cascades and activation of gene expression programs to
      orchestrate an adaptive response that will allow the cell to survive and resume
      its normal functioning. In this review we will focus on the transcription factor
      NFAT5, a fundamental regulator of the response to osmotic stress in mammalian
      cells. Identified in 1999, NFAT5 is the latest addition to the Rel family, which
      comprises the NF-kappaB and NFATc proteins. Though in some of its structural and
      functional features NFAT5 is a hybrid between these two major groups of Rel
      proteins, it has unique characteristics that make it stand on its own as a third
      type of Rel transcription factor. Since its discovery, NFAT5 has been studied
      mostly in the context of the hypertonicity stress response. The advent of mouse
      models deficient in NFAT5 and other recent advances have confirmed a fundamental
      osmoprotective role for this factor in mammals, but also revealed features that
      suggest it may have a wider range of functions.

PMID- 16904651
TI  - PAX genes: roles in development, pathophysiology, and cancer.
AB  - PAX proteins function as transcription factors and play an essential role in
      organogenesis during embryonic development in regulating cell proliferation and
      self-renewal, resistance to apoptosis, migration of embryonic precursor cells,
      and the coordination of specific differentiation programs. Recent studies have
      also discovered a role for PAX proteins in specific stem cell or progenitor cell
      populations, including melanocytes, muscle, and B-cells. The normal functions of
      the PAX proteins, including apoptosis resistance and repression of terminal
      differentiation, may be subverted during the progression of a number of specific
      malignancies. This is supported by the fact that expression of PAX proteins is
      dysregulated in several different types of tumors, although the precise roles for
      PAX proteins in cancer are not clearly understood. An emerging hypothesis is that
      PAX proteins play an essential role in maintaining tissue specific stem cells by
      inhibiting terminal differentiation and apoptosis and that these functional
      characteristics may facilitate the development and progression of specific
      cancers. In this review, we provide a general background to the PAX protein
      family and focus on specific cells and tissues and the role PAX proteins play
      within these tissues in terms of development, mature tissue maintenance, and
      expression in tumors. Understanding the normal developmental pathways regulated
      by PAX proteins may shed light on potentially parallel pathways shared in tumors,
      and ultimately result in defining new molecular targets and signaling pathways
      for the development of novel anti-cancer therapies.

PMID- 16904652
TI  - Oxytocin increases retention of social cognition in autism.
AB  - BACKGROUND: Oxytocin dysfunction might contribute to the development of social
      deficits in autism, a core symptom domain and potential target for intervention.
      This study explored the effect of intravenous oxytocin administration on the
      retention of social information in autism. METHODS: Oxytocin and placebo
      challenges were administered to 15 adult subjects diagnosed with autism or
      Asperger's disorder, and comprehension of affective speech (happy, indifferent,
      angry, and sad) in neutral content sentences was tested. RESULTS: All subjects
      showed improvements in affective speech comprehension from pre- to post-infusion;
      however, whereas those who received placebo first tended to revert to baseline
      after a delay, those who received oxytocin first retained the ability to
      accurately assign emotional significance to speech intonation on the speech
      comprehension task. CONCLUSIONS: These results are consistent with studies
      linking oxytocin to social recognition in rodents as well as studies linking
      oxytocin to prosocial behavior in humans and suggest that oxytocin might
      facilitate social information processing in those with autism. These findings
      also provide preliminary support for the use of oxytocin in the treatment of
      autism.

PMID- 16904653
TI  - Acetylcholinesterase modulates stress-induced motor responses through catalytic
      and noncatalytic properties.
AB  - BACKGROUND: Cholinergic neurotransmission notably participates in stress-induced
      motor responses. Here we report the contribution of alternative splicing of
      acetylcholinesterase (AChE) pre-mRNA to modulate these responses. More
      specifically, we induced stress-associated hypofunction of dopaminergic, mainly
      D2 dopamine receptor-mediated neurotransmission by haloperidol and explored
      stress induced hyperlocomotion and catalepsy, an extreme form of immobility,
      induced in mice with AChE deficiencies. METHODS: Conditional transgenic (Tet/AS)
      mice were created with tetracycline-induced antisense suppression of AChE gene
      expression. Locomotion and catalepsy times were measured in Tet/AS and strain
      matched control mice, under open-field exposure threat and under home-cage
      safety. RESULTS: In vitro, NGF-treated PC12 cells failed to extend neurites upon
      Tet/AS suppression. In vivo, Tet/AS but not control mice showed stress-associated
      hippocampal deposits of heat-shock protein 70 and GRP78 (BiP), predicting
      posttranscriptional changes in neuronal reactions. Supporting this notion, their
      striatal cholinergic neurons demonstrated facilitated capacity for neurite
      extension, attributing these in vivo changes in neurite extension to network
      interactions. Tet/AS mice presented stress-induced hyperlocomotion. Moreover, the
      dopamine antagonist haloperidol induced longer catalepsy in threatened Tet/AS
      than in control mice. When returned to home-cage safety, Tet/AS mice showed
      retarded release from catalepsy. CONCLUSIONS: Acetylcholinesterase modulates
      stress-induced motor responses and facilitates resumption of normal motor
      behavior following stress through both catalytic and noncatalytic features.

PMID- 16904654
TI  - Acute ethanol administration decreases GAP-43 and phosphorylated-GAP-43 in the
      rat hippocampus.
AB  - Acute alcohol ingestion is well known to have deleterious effects on memory and
      also known to inhibit long-term potentiation, a putative cellular substrate of
      memory. In this study, we for the first time revealed that growth-associated
      protein 43 (GAP-43), which is well known as a presynaptic substrate of protein
      kinase C and one of the major synaptic plasticity-related genes, was down
      regulated by single ethanol administration (2.5 g/kg, 15% in saline, i.p.) in the
      rat hippocampus. Using real-time PCR, we confirmed that GAP-43 mRNA level is
      significantly decreased 2 h after ethanol administration. GAP-43 and p-GAP-43
      (Ser41) immunoreactivities in the hippocampus were also reduced 4 h after ethanol
      administration. Immunohistochemical study showed that the reduction of GAP-43 and
      p-GAP-43 expression was associated with the perforant and mossy fibers pathways.
      These results suggest that the reduction of GAP-43 in the hippocampus might be,
      at least in part, a cause of memory impairment after acute ethanol ingestion.

PMID- 16904655
TI  - Prospective evaluation of malignant middle cerebral artery infarction with blood
      brain barrier imaging using Tc-99m DTPA SPECT.
AB  - BACKGROUND: Malignant middle cerebral artery (MMCA) infarction is associated with
      severe brain edema which may lead to a rapid deterioration of consciousness,
      increase of intracranial pressure, brain midline shift and finally, herniation.
      We examined the correlation between the degree of the blood-brain barrier (BBB)
      permeability and MMCA. METHODS: Twenty-five consecutive patients (17 men and 8
      women, mean age 62.1+/-10.1) were included in the study. Each patient had a daily
      clinical examination, and the neurological deficits were scored using NIHSS
      score. A CT without contrast material was performed in all patients. (99m)Tc-DTPA
      SPECT was performed at 36 h after the stroke. A quantitative index of BBB
      breakdown (disruption index) was calculated. RESULTS: The mean volume of stroke
      was 138+/-87 cm(3). The mean DTPA disruption index was 6.6+/-4.6 (range 1.0
      21.0). The mean NIHSS score was 14+/-4 (p=0.2). Five of 25 patients had brain
      herniation as evidenced on brain CT. The volume of stroke was only marginally
      elevated in patients with herniation (p=0.062). All patients showed significant,
      inverse correlation between NIHSS score and DTPA uptake (r=-0.43, p=0.033). There
      was a significant correlation between the extent of DTPA distribution (more than
      one vascular territory) and the occurrence of herniation (p<0.001). CONCLUSIONS:
      DTPA-SPECT imaging is a reliable complementary predictive tool in patients with
      an MCA stroke. The specific pattern found on DTPA SPECT, compatible with diffuse
      BBB disruption, may be of value in predicting "malignant MCA."

PMID- 16904656
TI  - Effects of electrical stimulation of the glossopharyngeal nerve on cells in the
      nucleus of the solitary tract of the rat.
AB  - Electrophysiological responses to electrical stimulation of the lingual branch of
      the glossopharyngeal (GP) nerve (which innervates taste buds on the caudal 1/3 of
      the tongue) were recorded from single cells in the rostral nucleus of the
      solitary tract (NTS) of anesthetized rats. Electrical stimulation was delivered
      as single pulses (n=55), paired-pulses (n=15) and tetanic trains (n=11). NTS
      cells with GP-evoked responses were also tested for responsivity to taste stimuli
      (0.1 M NaCl, 0.5 M sucrose, 0.01 M HCl and 0.01 M quinine HCl). Fifty-five
      neurons were studied: 49 cells showed GP-evoked (mean latency+/-SEM=18.0+/-1.32
      ms); seven of these were taste-responsive. Spontaneous rate of these cells was
      low (mean+/-SEM=1.4+/-0.3 spikes per second; median=0.21 spikes per second) and
      many cells showed no spontaneous activity. Paired-pulse stimulation of the GP
      nerve in 13 rats produced both paired-pulse suppression (n=11) and paired-pulse
      enhancement (n=4); tetanic stimulation (25 Hz, 1.0 s) produced sustained (>20 s)
      increases or decreases in firing rate in 7 of 11 cells tested. Histological data
      suggested that GP-evoked responses recorded in the most rostral NTS were likely
      the result of polysynaptic connections. Cells with GP-evoked responses formed a
      heterogeneous group in terms of their response properties and differed from cells
      with evoked responses to chorda tympani (CT; which innervates taste buds on the
      rostral 1/3 of the tongue) nerve stimulation. These differences may reflect the
      respective functional specializations of the GP and CT nerves.

PMID- 16904657
TI  - Spatiotemporal profile of dendritic outgrowth from newly born granule cells in
      the adult rat dentate gyrus.
AB  - Neurogenesis in the adult dentate gyrus occurs in the subgranular zone where
      newborn neurons (NNs) migrate a short distance into the granule cell layer and
      extend their rudimentary apical dendritic processes upon a radial glial scaffold.
      Using doublecortin (DCX) immunocytochemistry, these growing dendrites can be
      visualized because dendritic growth cones, including filipodia and lamellipodia,
      are labeled in both light and electron microscopic preparations. To study the
      rate of dendritic outgrowth of newborn dentate granule cells, single injections
      of 5-bromo-2-deoxyuridine (BrdU) with different survival times were combined with
      double immunolabeling for BrdU and DCX. At the earliest time points (4 and 12 h
      after BrdU injections), a rudimentary process can be observed to emanate from
      BrdU/DCX double-labeled cells. By 48 h the dendrites first appeared in the
      molecular layer. By 96 h after BrdU injection, these apical dendrites extended
      into the middle of the molecular layer where they ramified. The calculated rate
      of dendritic growth for NNs was about 15 microm per day for the first 3 days, and
      then a doubling in length occurred at 4 and 5 days that coincided with a
      retraction of the basal dendrite. In addition, electron microscopy of DCX-labeled
      apical dendrites showed that they were much thinner (1/4 to 1/3 the size) in
      diameter than unlabeled, mature apical dendrites and that they had developing
      synapses on them in the molecular layer.

PMID- 16904658
TI  - Neurophysiological evidence for selective auditory attention deficits in children
      with specific language impairment.
AB  - Recent behavioral studies suggest that children with poor language abilities have
      difficulty with attentional filtering, or noise exclusion. However, as behavioral
      performance represents the summed activity of multiple stages of processing, the
      temporal locus of the filtering deficit remains unclear. Here, we used an event
      related potential (ERP) paradigm to compare the earliest mechanisms of selective
      auditory attention in 12 children with specific language impairment (SLI) and 12
      matched control children. Participants were cued to attend selectively to one of
      two simultaneously presented narrative stories. The stories differed in location
      (left/right speaker), narration voice (male/female), and content. ERPs were
      recorded to linguistic and nonlinguistic probe stimuli embedded in the attended
      and unattended story. By 100 ms, typically developing children showed an
      amplification of the sensorineural response to attended as compared to unattended
      stimuli. In contrast, children with SLI showed no evidence of sensorineural
      modulation with attention, despite behavioral performance indicating that they
      were performing the task as directed. These data are the first to show that SLI
      children have marked and specific deficits in the neural mechanisms of attention
      and, further, localize the timing of the attentional deficit to the earliest
      stages of sensory processing. Deficits in the effects of selective attention on
      early sensorineural processing may give rise to the diverse set of sensory and
      linguistic impairments in SLI children.

PMID- 16904659
TI  - Brain monoaminergic neurotransmission parameters in weanling rats after perinatal
      exposure to methylmercury and 2,2',4,4',5,5'-hexachlorobiphenyl (PCB153).
AB  - The individual and joint effects of methylmercury (MeHg; 1 mg/kg body weight/day,
      GD7-PND7) and PCB153 (20 mg/kg body weight/day, GD10-GD16), administered orally
      to rat dams, were explored in 21-day-old rat offspring brain in terms of
      monoamine oxidase B (MAO-B) activity and regional content of dopamine (DA),
      serotonin (5-HT), 5-hydroxy-indole-3-acetic acid (5-HIAA) and homovanillic acid
      (HVA). Neither treatment altered MAO-B in striatum, hippocampus, cerebellum and
      cerebral cortex of female pups. In males the cerebellum displayed a significantly
      reduced enzyme activity (25-45%) following all treatments. Concerning biogenic
      amines, 5-HT levels were decreased by 30-50% in the cerebral cortex of males and
      females by PCB153 alone and combined with MeHg, without changes in 5-HIAA and
      dopaminergic endpoints. In cerebellum of all pups, MeHg enhanced 5-HIAA levels,
      whereas PCB153, either alone or combined with MeHg, did not affect this endpoint.
      In striatum, PCB153 reduced the content of DA, HVA and 5-HIAA (respective control
      values: 2-3; 60-80; 8-10 ng/mg protein) to a similar extent when administered
      alone or together with MeHg (20-40%). Perinatal exposure to MeHg and/or PCB153
      results in regionally and/or gender-specific alterations in the central
      dopaminergic and serotonergic systems at weaning. The combined treatment with
      MeHg and PCB153 does not exacerbate the neurochemical effects of the individual
      compounds.

PMID- 16904660
TI  - Alterations in spatial learning and memory after forced exercise.
AB  - Exercise has been shown to influence learning and memory. Most studies were
      performed with a voluntary running paradigm (e.g. running wheel) in mice.
      However, such effects of exercise on learning and memory are less well
      demonstrated using a forced running paradigm (e.g. treadmill). The present study
      was designed to examine the effects of 12 weeks of forced treadmill running on
      learning and memory performance in rats. We have previously shown that forced
      running resulted in qualitative and quantitative changes in the cholinergic
      neurons of the horizontal diagonal band of Broca (HDB) in the septum. This study
      was conducted in order to determine whether or not these changes occur
      simultaneously with enhanced learning and memory. The one-day version of the
      Morris water maze (MWM) test [Frick, K.M., Stillner, E.T., Berger-Sweeney, J.,
      2000. Mice are not little rats: species differences in a one-day water maze task.
      NeuroReport 11, 3461-3465] was used to test spatial learning and memory after the
      exercise period. Our data showed that runners displayed better spatial learning
      and memory when compared to nonrunners. This was evidently shown by a reduction
      in the time required for spatial acquisition (p<0.05) and superior probe trial
      performance (p<0.05). A shorter distance swam by the runners also suggested
      improved learning over the nonrunners (p<0.05). In an attempt to revalidate our
      earlier quantitative results, we used design-based stereology (DBS) to estimate
      the number of cholinergic neuronal profile population in the medial septum and
      diagonal band (MSDB). We confirmed that forced running increased the cholinergic
      neuronal profile subpopulation in the HDB (Coefficient of Error<0.2). Taken
      together, these results indicate that forced exercise could influence learning
      and memory with a concomitant increase in the number of cholinergic neurons in
      the HDB.

PMID- 16904661
TI  - Expression of the short stature homeobox gene Shox is restricted by proximal and
      distal signals in chick limb buds and affects the length of skeletal elements.
AB  - SHOX is a homeobox-containing gene, highly conserved among species as diverse as
      fish, chicken and humans. SHOX gene mutations have been shown to cause idiopathic
      short stature and skeletal malformations frequently observed in human patients
      with Turner, Leri-Weill and Langer syndromes. We cloned the chicken orthologue of
      SHOX, studied its expression pattern and compared this with expression of the
      highly related Shox2. Shox is expressed in central regions of early chick limb
      buds and proximal two thirds of later limbs, whereas Shox2 is expressed more
      posteriorly in the proximal third of the limb bud. Shox expression is inhibited
      distally by signals from the apical ectodermal ridge, both Fgfs and Bmps, and
      proximally by retinoic acid signaling. We tested Shox functions by overexpression
      in embryos and micromass cultures. Shox-infected chick limbs had normal proximo
      distal patterning but the length of skeletal elements was consistently increased.
      Primary chick limb bud cell cultures infected with Shox showed an initial
      increase in cartilage nodules but these did not enlarge. These results fit well
      with the proposed role of Shox in cartilage and bone differentiation and suggest
      chick embryos as a useful model to study further the role of Shox in limb
      development.

PMID- 16904662
TI  - Differential gene expression and functional analysis implicate novel mechanisms
      in enteric nervous system precursor migration and neuritogenesis.
AB  - Enteric nervous system (ENS) development requires complex interactions between
      migrating neural-crest-derived cells and the intestinal microenvironment.
      Although some molecules influencing ENS development are known, many aspects
      remain poorly understood. To identify additional molecules critical for ENS
      development, we used DNA microarray, quantitative real-time PCR and in situ
      hybridization to compare gene expression in E14 and P0 aganglionic or wild type
      mouse intestine. Eighty-three genes were identified with at least two-fold higher
      expression in wild type than aganglionic bowel. ENS expression was verified for
      39 of 42 selected genes by in situ hybridization. Additionally, nine identified
      genes had higher levels in aganglionic bowel than in WT animals suggesting that
      intestinal innervation may influence gene expression in adjacent cells.
      Strikingly, many synaptic function genes were expressed at E14, a time when the
      ENS is not needed for survival. To test for developmental roles for these genes,
      we used pharmacologic inhibitors of Snap25 or vesicle-associated membrane protein
      (VAMP)/synaptobrevin and found reduced neural-crest-derived cell migration and
      decreased neurite extension from ENS precursors. These results provide an
      extensive set of ENS biomarkers, demonstrate a role for SNARE proteins in ENS
      development and highlight additional candidate genes that could modify
      Hirschsprung's disease penetrance.

PMID- 16904664
TI  - Pathogenic mechanisms in Alzheimer's disease.
AB  - Alzheimer's disease is a progressive neurodegenerative disorder associated with
      aging and characterized by neurofibrillary tangles and amyloid plaques that
      deposit in the brain, triggering the neurodegenerative phenomena and leading to
      neuronal death. Amyloid plaques are primarily composed of beta-amyloid peptides,
      which derive from the Amyloid Precursor Protein (APP) upon the consequential
      action of beta- and gamma-secretase. This review discusses recent literature on
      beta- and gamma-secretase, and on those cellular factors, like cholesterol and
      phosphorylation of APP, that are involved in aging and may affect the function of
      both beta- and gamma-secretase.

PMID- 16904663
TI  - Differential expression of alpha1-adrenergic receptor subtypes in coronary
      microvascular endothelial cells in culture.
AB  - It has been postulated that in blood vessels under alpha(1)-related stimulation,
      the endothelial intracellular calcium concentration ([Ca(2+)](i)) increases,
      which is necessary to induce nitric oxide synthesis, is the result of an increase
      in vascular smooth muscle, which subsequently, flows into the endothelial cells
      through gap junctions and it is not the result of a direct adrenergic stimulation
      of endothelial receptors. Others, however, postulate that endothelial alpha(1D)
      adrenoceptors, have a direct effect on nitric oxide synthesis. In order to
      clarify this phenomena, in this work we analyzed the presence of alpha(1)receptor
      subtypes and their functional association with nitric oxide synthesis in rat
      coronary microvascular endothelial cells in culture, with pharmacological,
      immunological and reverse transcriptase polymerase chain reaction approaches. Our
      results show the presence and functional coupling with nitric oxide synthesis of
      alpha(1A) and alpha(1D)-adrenoceptor subtypes. alpha(1B)-adrenoceptor subtype is
      not coupled with nitric oxide production.

PMID- 16904665
TI  - Expression of liver-enriched nuclear factors and their isoforms in alpha
      fetoprotein-producing gastric carcinoma cells.
AB  - Alpha-fetoprotein (AFP)-producing gastric cancer (AFP-GC) is a highly malignant
      variant of adenocarcinoma with aberrant hepatocellular phenotype. A detailed
      understanding of the regulation of its liver phenotype is lacking. Liver-enriched
      nuclear factors (LENFs) are implicated in the transcriptional regulation of AFP
      in the fetal liver. To investigate the regulatory role of LENFs in AFP-GCs, the
      expression of LENFs including CCAAT/enhancer binding protein (C/EBP)-beta, C/EBP
      alpha, hepatocyte nuclear factor (HNF)-1alpha, HNF-1beta and HNF-4alpha was
      investigated in 3 cell lines of AFP-GC and 7 cell lines of control GC. The liver
      activating protein (LAP), an activating isoform of C/EBP-beta, was predominantly
      expressed in AFP-GCs, whereas the liver inhibitory protein (LIP), an inhibitory
      isoform of C/EBP-beta, predominated in the control GCs. HNF-1alpha was relatively
      suppressed in AFP-GCs. HNF-4alpha was expressed in one of three AFP-GC cell
      lines. C/EBP-alpha and HNF-1beta were expressed at the same levels in both cell
      types of GC. AFP-GCs expressed a set of hepatocyte-related proteins (e.g.,
      transferrin and albumin) while they still retained the several glandular cell
      related proteins (e.g., MUC2). The induction of LIP reduced transferrin
      expression and induced CEA expression in an AFP-GC line. Collecting these
      results, it was suggested that the contribution of LENFs, especially isoforms of
      C/EBP-beta, is possibly important in phenotypic regulation of AFP-GCs.

PMID- 16904666
TI  - Rho kinase regulates phagocytosis, surface expression of GlcNAc, and Golgi
      fragmentation of apoptotic PC12 cells.
AB  - Apoptotic cells undergo a number of changes to prepare for phagocytosis; most
      occur during the execution phase of apoptosis, when dying cells undergo shrinkage
      and/or fragmentation into apoptotic bodies and express phagocytic markers on
      their surface. Although events during the execution phase are important to
      prepare corpses for phagocytosis, the mechanisms that control most execution
      phase events are unknown. To understand regulation of execution events we focused
      on Rho kinase (ROCK), because one isoform of ROCK, ROCK-I, is constitutively
      activated by caspases during execution. Using apoptotic PC12 cells as a model, we
      find that inhibition of ROCK activity during apoptosis decreases surface
      expression of GlcNAc, a carbohydrate known to function as a phagocytic marker. In
      addition, inhibition of ROCK blocks Golgi fragmentation in apoptotic cells, and
      constitutively active ROCK induces Golgi fragmentation in the absence of
      apoptosis. Importantly, PC12 cells dying in the presence of a ROCK inhibitor are
      less efficiently phagocytized than those dying without the inhibitor. These data
      highlight the role of ROCK in multiple processes in the execution phase of
      apoptosis, and suggest that ROCK plays an important role in controlling the
      outcome of apoptosis, that is, preparation of corpses for phagocytosis.

PMID- 16904668
TI  - Ixodes ricinus: the potential of two-dimensional gel electrophoresis as a tool
      for studying host-vector-pathogen interactions.
AB  - Ixodes ricinus is a three-host tick, with three active instars. For moulting to
      occur the tick has to find a host where it can take a blood meal. Throughout
      feeding I. ricinus can be infected or infect the host with different pathogens,
      e.g., Tick-Borne Encephalitis virus or Borrelia burgdorferi. The host-vector
      pathogen interaction is very complex, making a detailed study difficult. Here we
      analyse the potential of two-dimensional gel electrophoresis (2DE) to study the
      host-vector-pathogen interaction. We examined 20 nymphs, which as larvae
      parasitised either mouse or hen. After moulting, they were kept alive for up to
      30 weeks, to analyse whether tick ageing influenced host determination, and for
      comparison of the 2D-gels. Even though the number of proteins in the gel
      decreased during ageing, some proteins of the host determination persisted for
      all 30 weeks. We also discovered persisting proteins in relation to nymphs. These
      findings showed that 2DE is suitable as a tool for studying host-vector-pathogen
      interactions.

PMID- 16904667
TI  - Ghrelin as a novel locally produced relaxing peptide of the iris sphincter and
      dilator muscles.
AB  - Ghrelin is a recently described acylated peptide, which works as a
      somatosecretagogue and has described effects on the smooth, skeletal and cardiac
      muscle. We examined the production and effects of ghrelin on relaxation of the
      iris muscles. Contractile effects of 1-5 human ghrelin (frGhr, 10(-9)-6 x 10(
      5)M) and 1-5 human des-octanoyl-ghrelin (d-frGhr; 10(-9)-6 x 10(-5)M) were tested
      on iris rabbit sphincter (n=11 frGhr; n=7 d-frGhr), dilator (n=6 frGhr; n=6 d
      frGhr) and rat sphincter (n=6 frGhr; n=8 d-frGhr) precontracted muscles. On
      rabbit sphincter the effect of frGhr was also tested in presence of: i) L-NA (10(
      5)M; n=7); ii) indomethacin (10(-5)M; n=7); iii) DLys(3)GHRP6 (10(-4)M; n=6); and
      iv) apamin+carybdotoxin (10(-6)M; n=6). Furthermore, on rabbit dilator the effect
      of frGhr was tested in presence of DLys(3)GHRP6 (10(-4)M; n=7). Finally, ghrelin
      mRNA production was assessed by "in situ" hybridization in Wistar rat eyes (n=8).
      In all muscles, frGhr promoted a concentration-dependent relaxation, maximal at 6
      x 10(-5)M, 1.5-3 min after its addition, decreasing tension by 34.1+/-12.1%,
      25.8+/-4.8% and 52.1+/-10.3% in the rabbit sphincter, dilator and rat sphincter,
      respectively. In the rabbit sphincter the relaxing effects of frGhr were: (i)
      enhanced in presence of DLys(3)GHRP6 (118.1+/-21.1%); (ii) blunted by
      indomethacin; and (iii) not altered by apamin+carybdotoxin (36.4+/-14.4%) or L-NA
      (52.4+/-11.4%). Relaxing effects of d-frGhr in rabbit (43.3+/-5.2%) and rat
      (77.1+/-15.3%) sphincter muscles were similar to those of frGhr. In rabbit
      dilator muscle, d-frGhr did not significantly alter active tension and the
      relaxing effect of frGhr was blunted by GHSR-1a blockage. Ghrelin mRNA was
      identified in iris posterior epithelium. In conclusion, ghrelin is a novel,
      locally produced, relaxing agent of iris dilator and sphincter muscles, an effect
      that is mediated by GHSR-1a in the former, but not in the latter. Furthermore, in
      the sphincter it seems to be mediated by prostaglandins, but not by NO or K(Ca)
      channels.

PMID- 16904669
TI  - TRIM11 binds to and destabilizes a key component of the activator-mediated
      cofactor complex (ARC105) through the ubiquitin-proteasome system.
AB  - TRIM11 is a member of the tripartite-motif-containing protein family and is known
      to destabilize humanin, an inhibitor of Alzheimer-like neuronal insults. In this
      study, we demonstrate that TRIM11 interacts with activator-recruited cofactor 105
      kDa component (ARC105) that mediates chromatin-directed transcription activation
      and is a key regulatory factor for transforming growth factor beta (TGFbeta)
      signaling. Co-expression of TRIM11 increased ARC105 degradation but a proteasome
      inhibitor suppressed this. Co-expression of TRIM11 and ARC105 also increased
      ubiquitination of ARC105. In addition, TRIM11 suppressed ARC105-mediated
      transcriptional activation induced with TGFbeta in a reporter assay. These
      results suggest that TRIM11, with the ubiquitin-proteasome pathway, regulates
      ARC105 function in TGFbeta signaling.

PMID- 16904670
TI  - Nuclear bile acid receptor FXR as pharmacological target: are we there yet?
AB  - The farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily
      that is primarily expressed in the enterohepatic system where it functions as
      intracellular sensor for bile acids. Ligand dependent FXR activation induces
      transcriptional responses to coordinately regulate bile acid, cholesterol,
      triglyceride and glucose metabolism, and to protect the intestinal mucosa from
      bacterial overgrowth and inflammatory insults. Here we discuss the latest
      discoveries in FXR-driven metabolic pathways with relevance to pathophysiology
      and novel therapeutic approaches of several conditions such as
      hypertriglyceridemia, type 2 diabetes, cholesterol gallstone disease, steato
      hepatitis and metabolic syndrome.

PMID- 16904671
TI  - NMR studies of the fifth transmembrane segment of Na+,K+-ATPase reveals a non
      helical ion-binding region.
AB  - The structure of a synthetic peptide corresponding to the fifth membrane-spanning
      segment (M5) in Na(+),K(+)-ATPase in sodium dodecyl sulfate (SDS) micelles was
      determined using liquid-state nuclear magnetic resonance (NMR) spectroscopy. The
      spectra reveal that this peptide is substantially less alpha-helical than the
      corresponding M5 peptide of Ca(2+)-ATPase. A well-defined alpha-helix is shown in
      the C-terminal half of the peptide. Apart from a short helical stretch at the N
      terminus, the N-terminal half contains a non-helical region with two proline
      residues and sequence similarity to a non-structured transmembrane element of the
      Ca(2+)-ATPase. Furthermore, this region spans the residues implicated in Na(+)
      and K(+) transport, where they are likely to offer the flexibility needed to
      coordinate Na(+) as well as K(+) during active transport.

PMID- 16904673
TI  - Spotlight on... Varda Rotter. Interview by Tine Walma.

PMID- 16904672
TI  - Possible role of avian uncoupling protein in down-regulating mitochondrial
      superoxide production in skeletal muscle of fasted chickens.
AB  - Little is known about the precise physiological roles of uncoupling protein 1
      (UCP1) homologs (UCP2, UCP3, avian UCP) whose levels are up-regulated during
      fasting. UCPs in skeletal muscle are thought to play a role in the regulation of
      lipids as fuel substrates, and/or in controlling the production of reactive
      oxygen species (ROS). The aim of this investigation, using skeletal muscle from
      fasted chickens, was to examine alterations in the expression of genes encoding
      for avian UCP and key enzymes relevant to lipid flux across the mitochondrial
      beta-oxidation pathway. We also clarified whether an increase in avUCP content
      could be associated with altered ROS production by mitochondria. Transcription
      levels of avUCP and CPT-I genes were increased 7.7- and 9.5-fold after a 24h fast
      and slightly diminished but remained about 5.0- and 7.7-fold higher than baseline
      levels, respectively, after 48h of fasting. In contrast, members of the beta
      oxidation pathway, LCAD and 3HADH, were gradually up-regulated from 12 to 48h of
      fasting. This suggests that processes involved in the transfer and oxidation of
      fatty acids are up-regulated differently during the initial stage of fasting.
      Analysis of ROS production by lucigenin-derived chemiluminescence showed that the
      FFA-sensitive portion of carboxyatractyloside-upregulated ROS production was
      greater in skeletal muscle mitochondria from 24h-fasted chickens compared with
      control, which leads us to postulate that ROS production is potentially down
      regulated by UCP. The possible involvement of a backlog of fatty acid for
      oxidation, observed in chickens after a 24h fast, in a transmembrane gradient of
      free non-oxidized fatty acids is also discussed.

PMID- 16904674
TI  - The effect of gonadal hormones and gender on anxiety and emotional learning.
AB  - Disorders of anxiety and fear dysregulation are highly prevalent. These disorders
      affect women approximately 2 times more than they affect men, occur predominately
      during a woman's reproductive years, and are especially prevalent at times of
      hormonal flux. This implies that gender differences and sex steroids play a key
      role in the regulation of anxiety and fear. However, the underlying mechanism by
      which these factors regulate emotional states in either sex is still largely
      unknown. This review discusses animal studies describing sex-differences in and
      gonadal steroid effects on affect and emotional learning. The effects of gonadal
      hormones on the modulation of anxiety, with particular emphasis on progesterone's
      ability to reduce the responsiveness of female rats to corticotropin releasing
      factor and the sex-specific effect of testosterone in the reduction of anxiety in
      male rats, is discussed. In addition, gonadal hormone and gender modulation of
      emotional learning is considered and preliminary data are presented showing that
      estrogen (E2) disrupts fear learning in female rats, probably through the
      antagonistic effect of ERalpha and ERbeta activation.

PMID- 16904675
TI  - Human resources and access to maternal health care.
AB  - The lack of human resources is one of the main bottlenecks to achieving the
      Millennium Development Goals on maternal and child health. A coherent national
      policy, recognized across government, needs to be in place to overcome this
      especially in countries severely affected by HIV/AIDS. Such a policy should cover
      selection of pre-service students, the qualifications of trainers and training
      sites, supportive supervision, career path development, a package of carefully
      thought-out incentives for the retention of staff, strategies for interaction
      with communities, and an agreed-upon health staff HIV/AIDS policy. Without such
      coherent human resource planning, a large number of countries will fail to reduce
      maternal and newborn mortality.

PMID- 16904676
TI  - Women's right to health and the Millennium Development Goals: promoting
      partnerships to improve access.
AB  - The Millennium Development Goals (MGD) represent a commitment of 189 member
      states that adopted them during the Millennium Summit in September 2000. This UN
      General Assembly recognized that gender equality and women's empowerment are both
      central to achieving sustainable development by means of combating poverty,
      hunger and disease. Neither reproductive nor sexual health was explicitly
      articulated in the original MDGs and indicators-a critical omission, as globally
      women are more disadvantaged than men. However, a clear link exists between all
      of the MDGs and the reproductive and sexual health of women, who cannot
      contribute to sustainable development, unless their right to health is met
      through improved access. The FIGO 2006 World Report on Women's Health addresses
      many issues critical to the success of the MDGs, with a focus on how partnerships
      have become a crucial vehicle to improve access to health for women.

PMID- 16904677
TI  - The phylogeny of Myxosporea (Myxozoa) based on small subunit ribosomal RNA gene
      analysis.
AB  - The phylogeny of the Myxosporea was studied using the small-subunit ribosomal RNA
      gene sequences. Maximum parsimony and Bayesian inference were used to determine
      myxosporean phylogenetic relationships. The analysis included 120 myxosporean
      sequences retrieved from GenBank and 21 newly obtained sequences of myxosporeans
      representing nine genera. Members of the genera Palliatus and Auerbachia were
      sequenced for the first time. The phylogenetic analysis supported a split of
      myxosporeans into two main lineages separating most of freshwater species from
      marine ones as described by previous authors. In addition to the two main
      lineages, a third lineage consisting of three species was found (Sphaerospora
      truttae, Sphaerospora elegans and Leptotheca ranae) and additional exceptions to
      the marine/freshwater myxosporean split were recognised (Sphaeromyxa hellandi,
      Sphaeromyxa longa and Myxidium coryphaenoideum). All three myxosporean lineages
      were characterised by specific lengths of SSU rDNA sequences. The lineage of
      marine myxosporeans split into five well-defined clades. They consisted of
      species with a similar site of infection and spore morphology and were referred
      as the Parvicapsula clade, the Enteromyxum clade, the Ceratomyxa clade, the
      marine Myxidium clade and the Kudoa clade, respectively. The inner topology of
      the freshwater clade was more complex but the trend to branch according to site
      of infection was observed in this clade as well. Due to the number of sequences
      available, a histozoic (Myxobolus clade) predominated. Interestingly, five
      morphologically different species infecting urinary bladder clustered within the
      histozoic (Myxobolus) clade. The phylogenetic trees derived from this study
      differ in a number of respects from the current taxonomy of the myxosporeans,
      which suggests that several currently utilised characters may be homoplasious or
      that reliance on a single gene tree may not adequately reflect the phylogeny of
      the group.

PMID- 16904678
TI  - Importance of flow division on transition to turbulence within an arteriovenous
      graft.
AB  - Transitional blood flow in an arteriovenous graft under various conditions of
      flow division was examined through direct numerical simulation. This junction
      consists of an inlet vessel (prosthetic graft) connected to a host vessel (vein)
      at an acute angle (21.6 degrees ). Inlet Reynolds numbers, based on mean velocity
      and graft inlet diameter, ranged from 800 to 1400. Various flow divisions between
      the two ends of the host vessel (i.e., the proximal venous segment, PVS, and
      distal venous segment, DVS) were considered (PVS:DVS ratios of 100:0, 85:15,
      70:30 and 115:(15)). The numerical technique employed the spectral element method
      which is a high-order discretization ideally suited to the simulation of
      transitional flows in complex domains. High velocity and pressure fluctuations
      were observed for the PVS:DVS=70:30 and 85:15 cases and absent from the 100:0 and
      115:(15) cases; the results indicate the importance of flow division on the
      development of turbulence in this junction. Transition to turbulence was observed
      at Reynolds numbers as low as 1000 and 800 under flow divisions of 85:15 and
      70:30, respectively, significantly lower than the critical value of 2100. The
      frequency spectra of velocity fluctuations indicated a significant intensity
      within the frequency range of approximately 300Hz downstream of the junction. An
      adverse pressure gradient developed in the PVS when graft inflow divided into
      opposite directions in the junction. This pressure gradient had a destabilizing
      effect on the flow and enhanced transition to turbulence in the PVS. These
      findings suggest that measurements of in vivo flow rates at the inlet and outlets
      are critical for the accurate prediction of arteriovenous hemodynamics. A
      potential clinical application of these results might be to close off the DVS
      during graft construction to ensure a 100:0 flow division.

PMID- 16904679
TI  - Application of high-performance liquid chromatography-nuclear magnetic resonance
      coupling to the identification of limonoids from mahogany tree (Switenia
      macrophylla, Meliaceae) by stopped-flow 1D and 2D NMR spectroscopy.
AB  - Separation and characterization of limonoids from Switenia macrophylla
      (Meliaceae) by HPLC-NMR technique has been described. Analyses were carried out
      using reversed-phase gradient HPLC elution coupled to NMR (600 MHz) spectrometer
      in stopped-flow mode. Separated peaks were collected into an interface unit prior
      to NMR measurements, which were performed with suppression of solvent signals by
      shaped pulses sequences. Structure elucidation of the limonoids was attained by
      data obtained from 1H NMR, TOCSY, gHSQC and gHMBC spectra without conventional
      isolation that is usually applied in natural products studies.

PMID- 16904680
TI  - Arrangement of tris(phthalocyaninato) gadolinium triple-decker complexes with
      multi-octyloxy groups on water surface.
AB  - A series of five carefully designed tris(phthalocyaninato) gadolinium triple
      decker complexes [Pc(R)8]Gd[Pc(R')8]Gd[Pc(R'')8] (R=R'=R''=H; R=R'=H, R''=OC8H17;
      R=R''=H, R'=OC8H17; R=H, R'=R''=OC8H17; R=R'=R''=OC8H17) (1-5) were prepared and
      the film forming properties on water surface were systematically investigated.
      The limited mean molecular area obtained by pi-A isotherms revealed an "edge-on"
      conformation for all these compounds. UV-vis absorption spectra showed red
      shifted Q bands, indicating the formation of J aggregates and effective
      intermolecular interaction in solid film. Phthalocyanine rings were found to take
      tilted orientation with respect to the normal of substrate according to the
      polarized absorption spectroscopic measurements. Low angle X-ray diffraction
      results provide direct evidence and therefore clearly clarify the point, for the
      first time, that unsymmetrical triple-decker molecules pack on the water surface
      with the unsubstituted phthalocyanine ring set close to the water surface and the
      substituted phthalocyanine ligand with octyloxy groups lies on the top.

PMID- 16904681
TI  - Circular dichroism of crude oil and its derivatives. Role of permolecular
      structures.
AB  - Petrols with different octane numbers, diesel fuel and solutions of crude oil in
      toluene have been studied by the methods of absorption spectroscopy, circular
      dichroism spectroscopy and correlation spectroscopy of scattered light. Circular
      dichroism signal was registered for crude oil solutions in the spectral ranges
      corresponding to the measured earlier resonance absorption of asphaltene
      solutions in toluene. We show that the optical activity of crude oil solutions is
      due to the aggregation of asphaltene molecules in one spectral range and is
      intensified with the aggregation of asphaltene molecules in another spectral
      range. Petrols have no optical activity. The optical activity registered for
      diesel fuel is possibly due to the aggregation of asphaltene molecules.

PMID- 16904682
TI  - Simple expressions for diffusion coefficient determination of adsorption within
      spherical and cylindrical absorbents using direct simulation method.
AB  - Various analytical expressions for solute adsorption kinetics within porous
      absorbents of defined geometry (planar sheet, cylinder, and sphere) are available
      in the literature. However, these expressions are limited for practical numerical
      evaluation because they are based on infinite series. An investigation of these
      expressions has been carried out and then accurate but simple expressions derived
      that enable rapid determination of effective diffusion coefficients for
      adsorption within geometrically categorical absorbents. These involve directly
      fitting calculated kinetic adsorption curves to experimental ones. A simple one
      point method is also proposed to estimate the effective diffusion coefficient for
      an adsorption process within these simple geometrical absorbents as an initial
      value for a best fit.

PMID- 16904684
TI  - Determination of the parameters for the 1-pK triple-layer model of ion adsorption
      onto oxides from known parameter values for the 2-pK TLM.
AB  - Prior knowledge of the model parameters describing the metal oxide/simple
      electrolyte interface is frequently crucial to successful application of surface
      complexation modeling. On the basis of the parameter values for the 2-pK triple
      layer model recently published by Sverjensky, the parameters for the 1-pK TLM
      were determined. This was done by fitting (using the 1-pK model) the proton
      surface charge and ion adsorption isotherms generated by the 2-pK TLM. It was
      assumed that inner-layer capacitance was the same for both models. A strong
      correlation was found between ion adsorption constants of different electrolytes
      on the same oxide predicted by both models. Additionally, the 1-pK and 2-pK
      models predict different electrokinetic potentials in spite of very similar
      values of calculated surface charge and ion adsorption isotherms when the same
      value of outer-layer capacitance is assumed. Because the value of outer-layer
      capacitance practically does not influence surface charge and electrolyte
      adsorption isotherms, it can be treated as a freely adjusted parameter, the value
      of which can be estimated if we have measured the electrokinetic potential.

PMID- 16904683
TI  - Hydroxyapatite organofunctionalized with silylating agents to heavy cation
      removal.
AB  - Hydroxyapatite surface silylation with organosilane derivatives (H3CO)3SiR, R
      being the corresponding organic moieties CH2CH2CH2NH2, CH2CH2CH2NHCH2CH2NH2, and
      CH2CH2CH2NHCH2CH2NHCH2CH2NH2, was carried out to yield organofunctionalized
      nanomaterials, named HApR1, HApR2, and HApR3, respectively. The products were
      characterized by elemental analysis, infrared spectroscopy, X-ray diffraction,
      thermogravimetry, and (1P and 13C NMR in the solid state. The amounts of groups
      grafted onto surfaces were 0.75+/-0.05, 2.35+/-0.14, and 2.48+/-0.18 mmolg(-1)
      for HApRx (x=1,2,3) surfaces, respectively. Linear correlations between elemental
      analysis, mass loss, (31)P chemical shift data, and the characteristics of the
      chain of each alkoxysilane were observed. The organic basic centers distributed
      onto the external surface have the ability to adsorb divalent copper and cobalt
      cations from aqueous solution. The degree of adsorption obtained from batchwise
      processes showed the best performance of these synthesized nanomaterials when
      compared with the pristine hydroxyapatite.

PMID- 16904685
TI  - Acquisition, persistence, and species susceptibility of the Hz-2V virus.
AB  - Hz-2V, formerly called gonad-specific virus, is known to infect the reproductive
      organs of both males and females of the corn earworm Helicoverpa zea, rendering
      them agonadal or sterile. The primary mode of transmission is through mating by
      asymptomatic carrier moths. In this report we show that Hz-2V can be acquired by
      first instar larvae, through feeding on virus laced diet, although the incidence
      of agonadal condition was significantly lower. In a laboratory study, the virus
      appeared to persist for no more than three generations, with the incidence of
      agonadal progeny decreasing with each generation. Although, Hz-2V has been
      reported only from H. zea, in our tests when nine species of insects were
      artificially infected, four of the Noctuid species showed some signs of agonadal
      condition. Out of the remaining five species, the diamondback moth Plutella
      xylostella and the German cockroach Blatella germanica, showed no evidence of the
      virus in progeny of adults that were injected with Hz-2V, even after using the
      very sensitive PCR based assay.

PMID- 16904686
TI  - Insight into catalysis of nitrous oxide reductase from high-resolution structures
      of resting and inhibitor-bound enzyme from Achromobacter cycloclastes.
AB  - The difficult chemistry of nitrous oxide (N2O) reduction to gaseous nitrogen (N2)
      in biology is catalysed by the novel micro4-sulphide-bridged tetranuclear Cuz
      cluster of the N2O reductases (N2OR). Two spectroscopically distinct forms of
      this cluster have been identified as CuZ and CuZ*. We have obtained a 1.86 A
      resolution crystal structure of the pink-purple species of N2OR from
      Achromobacter cycloclastes (AcN2OR) isolated under aerobic conditions. This
      structure reveals a previously unobserved ligation with two oxygen atoms from
      H2O/OH- coordinated to Cu1 and Cu4 of the catalytic centre. We ascribe this
      structure to be that of the CuZ form of the cluster, since the previously
      reported structures of two blue species of N2ORs, also isolated aerobically, have
      characterised the redox inactive CuZ* form, revealing a single water molecule at
      Cu4. Exposure of the as-isolated AcN2OR to sodium iodide led to reduction of the
      electron-donating CuA site and the formation of a blue species. Structure
      determination of this adduct at 1.7 A resolution showed that iodide was bound at
      the CuZ site bridging the Cu1 and Cu4 ions. This structure represents the first
      observation of an inhibitor bound to the Cu1-Cu4 edge of the catalytic cluster,
      providing clear evidence for this being the catalytic edge in N2ORs. These
      structures, together with the published structural and spectroscopic data, give
      fresh insight into the mode of substrate binding, reduction and catalysis.

PMID- 16904687
TI  - The crystal structure of a thermophilic glucose binding protein reveals
      adaptations that interconvert mono and di-saccharide binding sites.
AB  - Periplasmic binding proteins (PBPs) comprise a protein superfamily that is
      involved in prokaryotic solute transport and chemotaxis. These proteins have been
      used to engineer reagentless biosensors to detect natural or non-natural ligands.
      There is considerable interest in obtaining very stable members of this
      superfamily from thermophilic bacteria to use as robust engineerable parts in
      biosensor development. Analysis of the recently determined genome sequence of
      Thermus thermophilus revealed the presence of more than 30 putative PBPs in this
      thermophile. One of these is annotated as a glucose binding protein (GBP) based
      on its genetic linkage to genes that are homologous to an ATP-binding cassette
      glucose transport system, although the PBP sequence is homologous to periplasmic
      maltose binding proteins (MBPs). Here we present the cloning, over-expression,
      characterization of cognate ligands, and determination of the X-ray crystal
      structure of this gene product. We find that it is a very stable (apo-protein Tm
      value is 100(+/- 2) degrees C; complexes 106(+/- 3) degrees C and 111(+/- 1)
      degrees C for glucose and galactose, respectively) glucose (Kd value is 0.08(+/-
      0.03) microM) and galactose (Kd value is 0.94(+/- 0.04) microM) binding protein.
      Determination of the X-ray crystal structure revealed that this T. thermophilus
      glucose binding protein (ttGBP) is structurally homologous to MBPs rather than
      other GBPs. The di or tri-saccharide ligands in MBPs are accommodated in long
      relatively shallow grooves. In the ttGBP binding site, this groove is partially
      filled by two loops and an alpha-helix, which create a buried binding site that
      allows binding of only monosaccharides. Comparison of ttGBP and MBP provides a
      clear example of structural adaptations by which the size of ligand binding sites
      can be controlled in the PBP super family.

PMID- 16904688
TI  - Psychiatric comorbidity in first episode schizophrenia: a 2 year, longitudinal
      outcome study.
AB  - OBJECTIVE: We have previously documented a high prevalence of Axis I psychiatric
      comorbidity in our patients with first episode psychosis. This study sought to
      determine the longitudinal impact of Axis I psychiatric comorbidity on patients
      with first episode schizophrenia (FES) and we hypothesised that patients with
      psychiatric comorbidity were associated with poorer clinical and functional
      outcomes. METHOD: One hundred and forty two consecutively hospitalized FES
      patients were included. Socio-demographic information was obtained and the PANSS,
      SUMD, GAF, WHOQOL-Bref were used to assess psychopathology, insight,
      social/occupational functioning and quality of life respectively at baseline and
      at 6, 12, 18 and 24 months after discharge. RESULTS: Over time and compared with
      baseline scores, patients with Axis I psychiatric comorbidity (n=46, 32.4%) had
      significantly less reduction of their PANSS total and subscale scores, less
      improvement in their awareness of their psychiatric illnesses and symptoms at 12,
      18 and 24 months and poorer insight into the consequences of their illness at 18
      and 24 months. Poor insight at baseline was correlated positively with PANSS
      negative symptom subdomain, and negatively with GAF at 24 months. CONCLUSION:
      Axis I Psychiatric comorbidity was associated with worse prospective outcomes in
      hospitalized patients with first episode schizophrenia, and this highlights a
      greater need towards the early recognition and management of these conditions.

PMID- 16904689
TI  - Association of a Met88Val diazepam binding inhibitor (DBI) gene polymorphism and
      anxiety disorders with panic attacks.
AB  - Several lines of evidence suggest that anxiety disorders have a strong genetic
      component, but so far only few susceptibility genes have been identified. There
      is preclinical and clinical evidence for a dysregulation of the central gamma
      aminobutyric acid (GABA)-ergic tone in the pathophysiology of anxiety disorders.
      Diazepam binding inhibitor (DBI) has been suggested to play a pivotal role in
      anxiety disorders through direct and indirect, i.e. via synthesis of neuroactive
      steroids, modulation of GABA(A) receptor function. These findings suggest that
      the DBI gene can be postulated as a candidate for a genetic association study in
      this disorder. Thus, single nucleotide polymorphisms (SNPs) of the DBI gene were
      investigated for putative disease associations in a German sample of anxiety
      disorder patients suffering from panic attacks and matched controls. We were able
      to detect a significant association between a non-synonymous coding variant of
      DBI with anxiety disorders with panic attacks. The rare allele of this
      polymorphism was more frequent in controls than in patients (OR=0.43; 95% CI:
      0.19-0.95). In conclusion, these results suggest a central role of DBI genetic
      variants in the susceptibility for the development of anxiety disorders that are
      characterized by the occurrence of panic attacks.

PMID- 16904690
TI  - Effects of moving training on histology and biomarkers levels of articular
      cartilage.
AB  - OBJECTIVE: To study the adaptation process and extent of articular cartilage in
      the canine knee joint to different modes of movements and to investigate if
      levels of cartilage oligomeric matrix protein (COMP), matrix metalloproteinases-1
      (MMP-1), matrix metalloproteinases-3 (MMP-3), and tissue inhibitor of matrix
      metalloproteinases-1 (TIMP-1) in serum and synovial fluid can be used to predict
      effectively early sports injury and remolding degree of articular cartilage in
      the canine knee. MATERIALS AND METHODS: Twenty adult dogs divided randomly into
      three groups (eight in the common training group, Training Group; eight in the
      intensified training group, Intensified Group; and four in the Control Group)
      were trained daily at different intensities. Magnetic resonance imaging (MRI)
      examinations were performed regularly (0, 2, 4, 6, 8, 10 weeks) to investigate
      changes of articular cartilage in the canine knee, while concentrations of COMP,
      MMP-1, MMP-3, and TIMP-1 in serum and synovial fluid were measured by ELISA
      assays. All of the dogs were euthanized after training for 10 weeks, and all of
      the knee joints were taken out to be examined histologically. RESULTS: We could
      find imaging changes of early sport injury of articular cartilage in the Training
      Group and Intensified Group by MRI examination after 2 weeks of training; the
      damage images were most severe in 4-6 weeks, and then lightened gradually. We
      could not find the difference of cartilage injury and repair degree in MRI images
      between these two groups at different time points. Elevations of levels of COMP,
      MMP-1, MMP-3, TIMP-1, and MMP-3/TIMP-1 in serum and synovial fluid were seen
      during the training period, and their levels changed remarkably at different
      times. Levels of MMP-1, MMP-3, and MMP-3/TIMP-1 in the Intensified Group were
      lower than that in the Training Group in general, and levels of COMP were higher,
      which hinted that the injury trend of articular cartilage in the Intensified
      Group was lower than that in the Training group, and the repair trend was higher.
      Furthermore, there were statistically significant associations between biomarker
      levels in serum and in synovial fluid. Histological examinations in 10 weeks
      demonstrated that the signs of cartilage damage and repair in canine knee joint
      in the Training Group and the Intensified Group were obvious, and the Intensified
      Group could do better than the Training Group in promoting remodeling
      reconstruction of articular cartilage. CONCLUSIONS: High-intensity and repetitive
      movement may easily induce sports injury, and it is followed with a repair
      process; intensified training can do better than common training in promoting
      remodeling reconstruction of articular cartilage. The sensitivity of these
      biomarkers reflecting articular cartilage pathological changes is better than
      MRI, and the associated application of several biomarkers to predict the extent
      of damage and repair, as well as changes of metabolism in articular cartilage,
      and to monitor change of disease course has very good value for clinical
      application.

PMID- 16904691
TI  - Clamping the supra-celiac aorta can effectively increase the success rate of
      orthotopic rat liver transplantation by increasing the tolerable time of the
      anhepatic phase.
AB  - BACKGROUND: Although using a Kamada model with a cuff approach for vascular
      anastomosis shortens the anhepatic time in orthotopic rat liver transplantation
      (ORLT), cardiac arrest is still often encountered during the anhepatic phase. We
      hypothesize that low cardiac output is the reason for this. In this study, we
      used the supra-celiac aorta clamp (SCAC) method during the anhepatic phase in
      ORLT to evaluate the success rate. MATERIALS AND METHODS: Spraque-Dawley rats
      were used in this the study. First, we tested the time between the clamping of
      the supra-hepatic inferior vena cava (IVC) clamped and cardiac arrest in between
      two groups according to whether SCAC was performed (n = 40) or not (n = 20).
      Clamping of the supra-hepatic IVC was performed 30 s or 1 min after SCAC (n = 20
      for each) in the SCAC group. Second, we performed the Kamada method for ORLT in
      two groups according to whether SCAC was performed (n = 20, 1-min SCAC) or not (n
      = 20). Successful ORLT was defined as a recipient rat surviving more then 5 days.
      RESULTS: The mean time between IVC clamping and cardiac arrest was longer in the
      group of 1-min SCAC group than in the 30-s SCAC group or without SCAC (19.8
      versus 11.45 versus 3.87 min, respectively, P < 0.001). The success rate of ORLT
      was higher in the SCAC group than in the group without SCAC (85% versus 15%,
      respectively, P < 0.001). CONCLUSIONS: SCAC can effectively increase the success
      rate of ORLT by increasing the tolerable time during the anhepatic phase. The
      reason for this is the avoidance of hypovolumic cardiac arrest during the
      anhepatic phase.

PMID- 16904692
TI  - Exogenous pro-angiogenic stimuli cannot prevent physiologic vessel regression.
AB  - BACKGROUND: In healing wounds, rising levels of vascular endothelial growth
      factor (VEGF) induce a period of robust angiogenesis. The levels of pro
      angiogenic factors in the wound begin to decline just before a period of vascular
      regression, suggesting that these mediators are necessary to sustain vessel
      density. The purpose of this study was to determine if the maintenance of pro
      angiogenic stimuli in the wound would prevent physiological vessel regression.
      MATERIALS AND METHODS: A standard subcutaneous sponge wound model was modified by
      the addition of a mini-osmotic pump, allowing manipulation of the wound milieu by
      the addition of exogenous growth factors. After initial characterization of this
      model, exogenous VEGF (10 microg/mL), FGF (10 microg/mL), PDGF (10 microg/mL), or
      VEGF (10 microg/mL) plus FGF (10 microg/mL) were delivered to wounds and blood
      vessel density analyzed by immunohistochemistry. RESULTS: VEGF administration
      resulted in a transient increase in wound vessel density (P < 0.05). None of the
      pro-angiogenic growth factors (VEGF, FGF, PDGF, VEGF/FGF) were able to prevent
      vascular regression (P = NS). CONCLUSIONS: These findings suggest that the anti
      angiogenic signals that mediate physiological vascular regression in wounds are
      strongly dominant over pro-angiogenic stimuli during the later phases of wound
      healing. Clinical manipulation of anti-angiogenic signals in addition to the
      currently used pro-angiogenic targets may be needed to achieve therapeutic
      modulation of blood vessel density.

PMID- 16904693
TI  - Application of bFGF and BDNF to improve angiogenesis and cardiac function.
AB  - BACKGROUND: Brain-derived neurotrophic factor (BDNF) is a survival factor for
      endothelial cells and expresses in the ischemic myocytes. The purpose of this
      study was to assess whether the simultaneous application of basic fibroblast
      growth factor (bFGF) and BDNF incorporating gelatin hydrogels improves
      angiogenesis and cardiac function in ischemic myocardium compared with bFGF
      applied alone. MATERIALS AND METHODS: Direct intramyocardial injection of 100
      microg of bFGF plus 25 microg of BDNF, 100 microg of bFGF, or saline were
      performed in canine infarct model. Colored microspheres were injected to assess
      the regional myocardial blood flow. Cardiac function was evaluated by cine
      magnetic resonance imaging (MRI). Immunohistochemical staining and enzyme linked
      immunosorbent assay (ELISA) were used to observe the localization and expression
      of bFGF and BDNF protein, and myocardial microvessel density was assessed by von
      Willebrand factor staining. RESULTS: Left ventricular ejection fraction (LVEF)
      was higher in bFGF plus BDNF group than in saline or bFGF group. Blood flow of
      the peri-infarct region was increased by bFGF plus BDNF treatment. The
      distribution of bFGF and BDNF-positive cardiomyocytes was similar in three
      groups. The expression of bFGF and BDNF protein and microvessel density in bFGF
      plus BDNF group was higher than in the other two groups. CONCLUSIONS: This study
      indicates that the sustained dual release of bFGF and BDNF incorporating gelatin
      hydrogels can improve angiogenesis and left ventricular function in the ischemic
      myocardium compared with bFGF applied alone. bFGF plus BDNF administration may be
      a promising therapeutic strategy for the treatment of ischemic myocardium.

PMID- 16904694
TI  - Is remote preconditioning as effective as direct ischemic preconditioning in
      preventing spinal cord ischemic injury?
AB  - BACKGROUND: Spinal cord injury remains a devastating complication of thoracic and
      thoracoabdominal aortic operations. The aim of this study was to assess the
      affectivity of direct ischemic preconditioning (PC) and remote PC in preventing
      spinal cord ischemic injury in an experimental model. MATERIALS AND METHODS:
      Thirty-eight New Zealand white rabbits were divided into five groups: One group
      served as Sham group (n = 7). Rabbits in other groups had their abdominal aorta
      cross-clamped for 40 min. Before aortic occlusion, aorta was clamped twice at the
      same site of aortic occlusion for 5 min followed by 15 min of reperfusion after
      each ischemic episode in one group (Direct PC, n = 8), left renal artery was
      clamped twice for 5 min followed by 15 min of reperfusion after each renal
      ischemic episode in one group (Remote PC, n = 8), left renal artery was first
      clamped for 5 min followed by 15 min of reperfusion and then aorta was clamped
      for 5 min followed by 15 min of reperfusion in one group (Remote + Direct PC, n =
      8), and no PC method was used in Control group (n = 7). RESULTS: In all PC
      groups, neurological status of rabbits (Tarlov score) at post-ischemia 24th and
      48th hours was better than the control group (P < 0.05), but worse than Sham
      group (P < 0.05). Mean viability index values in PC groups were higher than
      control group (P < 0.01). Post-ischemia serum NSE and MDA levels obtained in all
      three PC groups were significantly lower than control group (P < 0.05 and P <
      0.01). CONCLUSIONS: The use of direct ischemic PC and/or remote PC is an
      effective way of reducing spinal cord ischemic injury because of aortic
      occlusion, while direct PC is more effective. The combined use of direct PC and
      remote PC did not provide better protection.

PMID- 16904695
TI  - Portal triad occlusion induces endotoxin tolerance: role of portal congestion.
AB  - BACKGROUND: Portal triad occlusion (PTO) causes portal congestion and damages the
      intestinal mucosa, which is associated with portal endotoxemia. However,
      administration of a sublethal dose of endotoxin results in resistance to its
      toxic activities. We tested the hypothesis that portal congestion due to PTO
      induces endotoxin tolerance. MATERIALS AND METHODS: Rats were subjected to PTO
      for 15 min. In Group 1, male rats underwent laparotomy and, 48 h after the
      surgery, a lethal dose of Escherichia coli lipopolysaccharide was administered.
      In Group 2, rats were subjected to PTO for 15 min. Then a lethal dose of LPS was
      administered 48 h after surgery. Group 3 was treated the same as Group 2, except
      that PTO was performed with portosystemic shunt. Group 4 was also treated same as
      Group 2, except that rats received polymixin B and neomycin by gavage to
      eliminate intestinal luminal bacteria before PTO. Survival was examined after the
      administration of a lethal dose of LPS. Changes in plasma levels of cytokine are
      also measured after the administration of LPS. The portal endotoxin level in each
      group after PTO was measured. RESULTS: On survival test, only rats in Group 2 and
      Group 4 showed significantly higher survival rates. The portal endotoxin level
      was significantly elevated only in Group 2. The elevation of plasma cytokine
      levels (IL-6, TNF-alpha) and NO production (NO(2)(-)/NO(3)(-)) in Groups 2 and 4
      were inhibited compare to those in Groups 1 and 3. CONCLUSIONS: PTO induced LPS
      tolerance possibly due to portal congestion and subsequent visceral congestion.

PMID- 16904696
TI  - Cyclosporine inhibits endotoxin-induced vasodilation of isolated rat resistance
      arterioles.
AB  - BACKGROUND: An isolated arteriole fails to dilate in response to endotoxin unless
      a segment of aorta is included in the perfusion system. The unknown substance
      released by the aorta after exposure to endotoxin is dependent upon the NF-kappaB
      pathway and induces inducible nitric oxide synthase (iNOS) in the arteriole. The
      purpose of this study was to determine if cyclosporine A (CSA) that inhibits both
      NF-kappaB and iNOS would prevent the vasodilatory response to endotoxin.
      MATERIALS AND METHODS: Rats were injected with either 10 mg/kg of CSA or oil
      vehicle followed by the removal of a cremaster muscle. The feeding arteriole was
      isolated from the cremaster and mounted on micropipettes and pressurized to 70
      mmHg in a superfused tissue bath. After an hour equilibration to develop
      spontaneous tone, a 1 cm segment of aorta was placed in the superfusion system
      upstream from the arteriole and Salmonella enteriditis endotoxin was added to the
      buffer at a concentration of 2.5 microg/mL (ET) or continued infusion of buffer
      alone. Internal diameters of cannulated arterioles were measured with
      videomicroscopy and videocalipers for an additional hour. RESULTS: Arterioles
      downstream from an aorta exposed to vehicle but not endotoxin developed 22.8 +/-
      3.7% tone that remained unchanged over the following hour. Arterioles exposed to
      endotoxin started with 22.5 +/- 2.8% spontaneous tone and this fell over the
      following hour to 11.8 +/- 3.6%, P < 0.05. Pre-treatment of the rats with CSA
      tended to increase resting tone and completely prevented the loss of tone after
      endotoxin. CONCLUSIONS: Pre-treatment of the aortic segment with CSA resulted in
      the development of increased tone in the downstream arteriole and completely
      blocked the vasodilatory response to endotoxin. These results suggest that CSA or
      a similar compound may be useful in the treatment of septic shock.

PMID- 16904697
TI  - The importance of subjectivity in perceptual errors on the emergence of indirect
      reciprocity.
AB  - Indirect reciprocity is one mechanism that allows for unilateral resource giving
      among n-persons. Using analytical methods and computer simulations, previous
      studies have examined a number of strategies that make indirect reciprocity
      possible. In particular, previous investigations have concentrated on whether
      differentiating between justified and unjustified not-giving is important.
      However, whether or not a given strategy is ESS depends on the type of perceptual
      errors that are assumed. When errors are objective, regarding those who do not
      give to "bad" as "good" is critical. When perceptual errors are subjective,
      however, regarding those who give to "bad" as "bad" is critical. Since we believe
      that there is no guarantee that perceptual errors are shared among all
      individuals in a society, we argue that the latter moral principle may play a
      more important role in human interactions.

PMID- 16904698
TI  - Looking inside an invasion wave of cells using continuum models: proliferation is
      the key.
AB  - Recently, a suite of cell migration assays were conducted to investigate the
      migration of neural crest (NC) cells along the gut during the development of the
      enteric nervous system (ENS). The NC cells colonise the gastro-intestinal tract
      as a rostro-caudal wave. Local behaviour was shown to be controlled by position
      relative to the leading edge of the wavefront. The assays involved chick-quail
      grafting techniques allowing the total invading population to be considered as a
      two-species system. A two-species continuum model with logistic proliferation and
      a migration mechanism is developed here to simulate the chick-quail graft
      experiments and provide a means of looking at the processes occurring within the
      invasion wave. Five migration mechanisms are considered--linear diffusion, two
      cases of nonlinear diffusion, chemokinesis and chemotaxis. The model results
      agree with the experimental observations, regardless of the specific type of
      migration mechanism. The results show that NC cell invasion is driven by
      proliferation and cell motility at the leading edge of the wave. Furthermore,
      logistic proliferation exerts the dominant control on the system. This
      observation is confirmed by analysing some simplified invasion models. Once the
      basic experiments were mathematically replicated, the mathematical models were
      used in turn to make some predictions that were yet to be experimentally tested.
      This involved conducting a sensitivity analysis of the system by interrupting the
      proliferation and/or migration ability of the leading edge. Numerical results
      show that the system is stable against these changes. Of the three experiments
      suggested, one was carried out and the experimental results were concordant with
      the theoretical predictions. The outcome of two other suggested experiments are
      predicted and left for future experimental validation.

PMID- 16904699
TI  - Effects of beta-carboline alkaloids on the object recognition task in mice.
AB  - beta-carboline alkaloids are found in several medicinal plants and display a
      variety of actions on the central nervous, muscular and cardiovascular systems.
      The aim of the present study was to evaluate the effects of systemic
      administration of beta-carboline alkaloids on object recognition in mice. Adult
      Swiss mice received an intra-peritoneal injection (i.p.) of alkaloids (1.0, 2.5
      or 5.0 mg/kg) 30 min before training in an object recognition task. The fully
      aromatic beta-carbolines, harmine and harmol, induced an enhancement of short
      term memory (STM) at all doses tested when compared to controls. Harmaline, a
      dihydro beta-carboline and inverse agonist of the MK-801 binding site on the N
      methyl-d-aspartate (NMDA) receptor, also induced an enhancement of both short
      term memory (STM) and long-term memory (LTM). These results demonstrate that
      systemic administration of beta-carboline alkaloids can improve object
      recognition memory in mice.

PMID- 16904700
TI  - Chronic administration of pioglitazone attenuates intracerebroventricular
      streptozotocin induced-memory impairment in rats.
AB  - Memory impairment induced by intracerebroventricular (ICV) injection of
      streptozotocin (STZ) in rats is associated with impaired brain glucose and energy
      metabolism, oxidative stress and impaired cholinergic neurotransmission.
      Treatment with antioxidants and cholinergic agonists has been reported to produce
      beneficial effect in this model. However, no reports are available on drugs that
      improve glucose utilization and metabolism. In the present study, we evaluated
      the effects of pioglitazone on cognitive performance, oxidative stress and
      glucose utilization in ICV STZ injected rats (3 mg/kg, on day 1 and 3).
      Pioglitazone (10 and 30 mg/kg) was administered per oral (p.o.) for 14 days,
      starting 5 days prior to STZ injection. Cognitive performance was assessed using
      step-through passive avoidance and Morris water maze task. Malondialdehyde (MDA)
      and glutathione levels in brain were estimated as parameters of oxidative stress.
      Glucose utilization by brain was assessed as the amount of glucose consumed from
      the media by the brain. ICV STZ injected rats showed a severe deficit in learning
      and memory associated with increased MDA levels (+67.5%), decreased glutathione
      levels (-29.2%) and impaired cerebral glucose utilization (-44.4%). In contrast
      pioglitazone treatment improved cognitive performance, lowered oxidative stress
      and improved cerebral glucose utilization in ICV STZ rats. The present study
      demonstrates the beneficial effects of pioglitazone in the ICV STZ induced
      cognitive deficits, which can be exploited for the dementia associated with
      diabetes and age-related neurodegenerative disorder, where oxidative stress and
      impaired glucose and energy metabolism are involved.

PMID- 16904701
TI  - Ageing is associated with increased expression but decreased activity of CYP2E1
      in male Wistar rats.
AB  - The effect of ageing on CYP2E1 activity and its protein and mRNA contents was
      investigated in both adult (9 months) and senescent (24 months) male Wistar rats.
      The CYP2E1 activity (as measured by chlorzoxazone hydroxylation) was
      significantly decreased by 36% in senescent rats as compared to adult rats.
      However, this decrease of activity was not associated with a loss of protein
      content because the amount of both CYP2E1 protein and CYP2E1 mRNA did not
      decrease in senescent rats but rather increased, by 79% and 64% respectively, as
      compared to adult rats. Lipid peroxidation was increased significantly by 140%
      with ageing. The decrease in CYP2E1 activity could be explained by post
      translational modification of CYP2E1 proteins, due to an increase in oxidative
      stress in senescent animals, leading to a loss of their functionality. However,
      no changes in the extent of protein carbonyls were observed in the adult versus
      senescent rats (16.2 +/- 9.6 vs. 12.7 +/- 7.3 nmol/mg prot) and the major
      proteasome activity remained unchanged. With regards to the increase of CYP2E1
      expression, our results showed that the amount of hepatocyte nuclear factor
      1alpha mRNA, a transcription factor that positively regulates CYP2E1, was
      strongly increased (154%) in senescent rats.

PMID- 16904702
TI  - Molecular cloning and characterization of a novel V-ATPase associated protein,
      DVA9.2, from human dendritic cells.
AB  - The vacuolar proton-ATPase (V-ATPase) is a ubiquitous ATP-driven H(+) transporter
      that functions in numerous cell processes. Accumulating evidence shows important
      roles of V-ATPase in tumor metastasis and antigen presentation of dendritic cells
      (DC). A novel V-ATPase associated protein, designated as DVA9.2 (dendritic cell
      derived V-ATPase associated protein of 9.2 kDa), has been identified from a human
      DC cDNA library by large-scale random sequencing. Full length cDNA of DVA9.2
      encodes an 81-residue protein that shares 70-80% homology with human V-ATPase
      subunit M9.2. Distant relationship is also found with Vma21p, a yeast protein
      required for V-ATPase assembly. DVA9.2 contains a conserved domain, ATP synthase
      subunit H (pafm05493), and two membrane-spanning helices. DVA9.2 mRNA is
      detectable in several human tumor cell lines as well as some human normal cells
      and tissues. Moreover, the inducible expression of DVA9.2 mRNA in DC during
      maturation is observed. DVA9.2 displays integration with membrane and main
      localization in lysosome, endoplasmic reticulum and Golgi-associated organelles,
      only less at the plasma membrane. In addition, DVA9.2 is co-localized with V(0)
      sector subunit a. Silencing of DVA9.2 by small interfering RNA (siRNA) does not
      affect the V-ATPase activity in cell membrane fractions or attenuate the
      migration and invasion in breast cancer MDA-MB-231 cells. These results indicate
      that DVA9.2, as a novel V-ATPase-associated protein, is not essential for the
      activity of V-ATPase complex and may be involved in functions of DC.

PMID- 16904703
TI  - Quantifying the environmental impacts of artisanal fishing gear on Kenya's coral
      reef ecosystems.
AB  - The environmental impacts of artisanal fishing gear on coral reef ecosystems were
      studied in the multi-gear fishery of southern Kenya to evaluate which types of
      gear have the greatest impact on coral reef biodiversity. The gear types studied
      were large and small traps, gill nets, beach seines, hand lines and spear guns.
      Levels of coral damage, proportion of juvenile fish and discards, size and
      maturity stage at first capture were quantified and compared amongst the gear
      types. Results indicate that fishers using beach seines, spears and gill nets
      cause the most direct physical damage to corals. Spear fishers showed the highest
      number of contacts to live corals per unit catch followed by fishers using gill
      nets (12.6+/-1.8 and 5.9+/-2.0 coral contacts per kg fish caught per trip
      respectively). Apart from discarding 6.5% of their daily catch in the sea, as it
      was too small, beach seine fishers also landed the highest percentage of juvenile
      fish (68.4+/-15.7%), a proportion significantly higher (p<0.001) than in any
      other gear. The size and maturity stage at first capture for 150 of 195 species
      caught by all gear types was well below the lengths at which they mature. For
      example, 100% of Lethrinus xanthochilus, 99% of Lethrinus nebulosus and 94% of
      Lethrinus harak caught were juveniles. Across all gear types, 50.1+/-22.7% of the
      catch consisted of juvenile fish, indicating serious growth overfishing. Field
      assessment of levels of coral density showed that fishing grounds where beach
      seines were still in use had a significantly lower density than where beach
      seining was not used. This correlation is likely to arise in part because seines
      cannot be used in the most coral rich areas, and in part because coral loss is a
      consequence of seine use. On a per gear basis therefore, beach seines had the
      most impact on coral reef biodiversity. This study emphasizes the need to enforce
      restrictions on destructive gear and mesh sizes.

PMID- 16904704
TI  - Analysis of recent vessel arrivals and ballast water discharge in Alaska: toward
      assessing ship-mediated invasion risk.
AB  - Ships are a dominant vector for biological invasions through ballast water
      discharge (BWD) and hull fouling. Here, we provide a first comprehensive analysis
      of shipping in Alaska, summarizing (a) the number, type and origin of vessel
      arrivals to Alaska for 2003 and 2004, (b) the spatial and temporal variation in
      vessel traffic, and (c) the available data on ballast water discharge in order to
      prioritize locations for tracking biological invasions. Most arrivals were
      passenger vessels, followed by ferries and fishing vessels, all of which carried
      little ballast water. Regional and seasonal patterns in arrivals and BWD were
      unevenly distributed among vessel types. The majority of vessels reporting BWD
      were from foreign ports, and most of this ballast was untreated. The largest
      volumes of ballast were from tankers at Valdez and Kenai Peninsula ports.
      Although Alaska has few documented invasions, opportunities for ship-mediated
      transfer now appear high and warrant further scrutiny.

PMID- 16904705
TI  - Basic physiological biomarkers in adult female perch (Perca fluviatilis) in a
      chronically polluted gradient in the Stockholm recipient (Sweden).
AB  - By measuring a battery of basic physiological biomarkers and the concentration of
      SigmaDDT in adult female perch (Perca fluviatilis), an assumed aquatic pollution
      gradient was confirmed, with the city of Stockholm (Sweden) as a point source of
      anthropogenic substances. The investigation included an upstream gradient,
      westwards through Lake Malaren (46 km), and a downstream gradient, eastwards
      through the Stockholm archipelago (84 km). The results indicated a severe
      pollution situation in central Stockholm, with poor health status of the perch:
      retarded growth, increased frequency of sexually immature females, low
      gonadosomatic index, and disturbed visceral fat metabolism. SigmaDDT, measured as
      a pollution indicator, was 10-28 times higher than the background in perch from
      the Baltic Proper. Besides the main gradient other sources of pollution also
      influenced the response pattern of the measured biomarkers. In particular, there
      were strong indications of pollution coming from the Baltic Sea.

PMID- 16904706
TI  - Mistranslation and genetic variability: the effect of streptomycin.
AB  - Streptomycin is an aminoglycoside antibiotic that acts at the level of protein
      synthesis. Exposure to sublethal concentrations of this antibiotic increased
      significantly the number of Arg+ mutants derived from an Escherichia coli argE3
      (ochre) rpsL31 (streptomycin-resistant) strain. The vast majority of these
      mutants appeared on selective minimal medium plates with streptomycin (200 micro
      g/ml) during stationary phase, after 6-10 days incubation at 37 degrees C.
      Derivative mutD5 or mutL or mutS mutants, carrying a faulty epsilon subunit of
      DNA polymerase or a defective mismatch DNA-repair protein, respectively, also
      showed higher numbers of Arg+ mutants on selective medium with streptomycin than
      on medium without streptomycin. Interestingly, with these DNA-repair mutants
      about 50% of the Arg+ mutants generated in the presence of streptomycin appeared
      during the first 5 days of incubation. These observations suggest that the
      activities of these fidelity-repair proteins prevent in the parental strain the
      early appearance of the supernumerary Arg+ mutants on the selective medium with
      streptomycin. The appearance of Arg+ mutants on the plates with streptomycin was
      not significantly altered by recA, rpoS or dps mutations. A high percentage of
      the Arg+ mutants arising in the presence of streptomycin were streptomycin
      dependent for growth without arginine (Arg+ St-D). These types of mutants
      displayed a Ram (for ribosomal ambiguity) phenotype, manifested by increased
      misreading, assayed by in vitro and in vivo experiments and by leakiness on
      several selective minimal media. Genetic data indicated that these mutants carry
      a mutation located at about 74 min of the E.coli map that relieves the high
      translational fidelity conferred by the rpsL mutation. These studies suggest that
      the growth-limiting conditions of the assay system used, as well as the presence
      of streptomycin, which causes an increased production of altered proteins,
      favours the appearance and growth of compensatory Arg+ mutants.

PMID- 16904708
TI  - The acrylamide (S)-1 differentially affects Kv7 (KCNQ) potassium channels.
AB  - The family of Kv7 (KCNQ) potassium channels consists of five members. Kv7.2 and 3
      are the primary molecular correlates of the M-current, but also Kv7.4 and Kv7.5
      display M-current characteristics. M-channel modulators include blockers (e.g.,
      linopirdine) for cognition enhancement and openers (e.g., retigabine) for
      treatment of epilepsy and neuropathic pain. We investigated the effect of a
      Bristol-Myers Squibb compound (S)-N-[1-(3-morpholin-4-yl-phenyl)-ethyl]-3-phenyl
      acrylamide [(S)-1] on cloned human Kv7.1-5 potassium channels expressed in
      Xenopus laevis oocytes. Using two-electrode voltage-clamp recordings we found
      that (S)-1 blocks Kv7.1 and Kv7.1/KCNE1 currents. In contrast, (S)-1 produced a
      hyperpolarizing shift of the activation curve for Kv7.2, Kv7.2/Kv7.3, Kv7.4 and
      Kv7.5. Further, the compound enhanced the maximal current amplitude at all
      potentials for Kv7.4 and Kv7.5 whereas the combined activation/block of Kv7.2 and
      Kv7.2/3 was strongly voltage-dependent. The tryptophan residue 242 in S5, known
      to be crucial for the effect of retigabine, was also shown to be critical for the
      enhancing effect of (S)-1 and BMS204352. Furthermore, no additive effect on Kv7.4
      current amplitude was observed when both retigabine and (S)-1 or BMS204352 were
      applied simultaneously. In conclusion, (S)-1 differentially affects the Kv7
      channel subtypes and is dependent on a single tryptophan for the current
      enhancing effect in Kv7.4.

PMID- 16904707
TI  - Differential roles of NR2A and NR2B-containing NMDA receptors in LTP and LTD in
      the CA1 region of two-week old rat hippocampus.
AB  - The role of NMDA receptors in the induction of long-term potentiation (LTP) and
      long-term depression (LTD) is well established but which particular NR2 subunits
      are involved in these plasticity processes is still a matter of controversy. We
      have studied the effects of subtype selective NMDA receptor antagonists on LTP
      induced by high frequency stimulation (100 Hz for 1s) and LTD induced by low
      frequency stimulation (1 Hz for 15 min) in the CA1 region of hippocampal slices
      from 14 day old Wistar rats. Against recombinant receptors in HEK293 cells NVP
      AAM077 (NVP) was approximately 14-fold selective for NR2A vs NR2B receptors,
      whilst Ro 25-6981 (Ro) was highly selective for NR2B receptors. On NMDA receptor
      mediated EPSCs from Schaffer collaterals in CA1 neurones, NVP and Ro both reduced
      the amplitude but differentially affected the time constant of decay. The data
      are compatible with the selective effect of NVP (0.1 microM) and Ro (4 microM) on
      native NR2A and NBR2B receptors, respectively. NVP reduced both LTP and LTD
      whereas Ro reduced only LTP. Thus, LTP was reduced by 63% at 0.1 microM NVP and
      almost completely at 0.4 microM whereas 5 microM Ro reduced LTP by 45%. These
      data are consistent with a role for both NR2A and NR2B in the induction of LTP,
      under our experimental conditions. In comparison, LTD was unaffected by Ro (5
      microM) even in the presence of a glutamate uptake inhibitor threo-beta
      benzylaspartic acid (TBOA) to increase the concentration of glutamate at NR2B
      containing receptors. NVP (0.2-0.4 microM), however, produced a concentration
      dependent inhibition of LTD which was complete at 0.4 microM. The lack of effect
      of 0.1 microM NVP on LTD contrasts with its marked effect on LTP and raises the
      possibility that different NVP-sensitive NR2 subunit-containing NMDA receptors
      are required for LTP and LTD in this preparation.

PMID- 16904709
TI  - Endogenous activation of nicotinic receptors underlies sympathetic tone
      generation in neonatal rat spinal cord in vitro.
AB  - Without the brainstem, thoracic spinal cords of neonatal rats in vitro
      spontaneously generate tonic sympathetic nerve discharge (SND) in the splanchnic
      nerves. Activation of nicotinic receptors in cords is known to alter a repertoire
      of neurotransmitter releases to sympathetic preganglionic neurons (SPNs). Using
      in vitro nerve-cord preparations, we investigated whether endogenous nicotinic
      receptor activity is essential for SND genesis. Application of mecamylamine, an
      open-channel nicotinic receptor blocker, reduced SND in a progressive manner.
      Exogenous activation of nicotinic receptors by application of various nicotinic
      agonists generally excited SND at low agonistic concentrations. At higher
      concentrations, however, agonists induced biphasic responses characterized by an
      initial excitation followed by prolonged SND suppression. Whether ionotropic
      glutamate, GABA(A), or glycine receptors are downstream signals of nicotinic
      receptor activation was explored by pretreatment of cords with selective
      antagonists. The initial excitation of SND persisted in the presence of
      ionotropic glutamate receptor antagonists. In contrast, the SND suppression was
      partially reversed by glycine or GABA(A) receptor antagonists. Incubation of the
      cord in a low Ca(2+)/high Mg(2+) bath solution to block Ca(2+)-dependent synaptic
      transmission did not affect SND excitation induced by nicotinic agonists,
      confirming direct activation of postsynaptic nicotinic receptors on SPNs. In
      conclusion, the endogenous activity of nicotinic receptors is essential for SND
      genesis in the thoracic spinal cord. Nicotinic activation of glycinergic and
      GABAergic interneurons may provide a recurrent inhibition of SPNs for homeostatic
      regulation of sympathetic outflow.

PMID- 16904710
TI  - Body inversion effect without body sense: insights from deafferentation.
AB  - Like faces, human bodies are recognized via the configuration of their parts;
      their recognition is impaired by inversion. Processing of configural relations
      has been shown to depend on perceptual expertise with certain classes of objects.
      Because people see their own body and others' bodies frequently, humans are
      experts in the visual processing of human body postures. In addition, the
      observer's own on-line, multimodal body representation which heavily relies on
      current proprioception may play a crucial role in recognizing human body
      postures. We investigated whether static body posture recognition relied on
      current proprioceptive inputs or whether visual familiarity and stored body
      representations were sufficient. IW, who is deafferented (lost cutaneous touch
      and proprioception from his body), was tested on the recognition of upright and
      inverted human body postures, faces, and houses. As controls, IW showed an
      inversion effect for abstract, common, and rare human body postures as well as
      faces, but not houses. Results rule out a strong contribution of current afferent
      inputs to the recognition of human postures. The findings are discussed in terms
      of the role of the body schema in body posture recognition and how other
      contributions from one's own body may be involved in the visual processing of
      human bodies.

PMID- 16904711
TI  - Interaction between nociceptin/orphanin FQ (N/OFQ) and GABA in response to
      feeding.
AB  - Nociceptin/orphanin FQ (N/OFQ) and gamma aminobutyric acid (GABA) agonists have
      been shown to increase feed intake in mammals and birds. In this study, the
      effect of intracerebroventricular (icv) injection of the potent NOP receptor
      agonists Nociceptin (1-13) NH(2), the GABA(A) receptor antagonist bicuculline,
      and the GABA(A) receptor agonist muscimol on feed intake in cockerels was
      investigated. The icv injection of N/OFQ and muscimol increases feed intake. The
      effect of N/OFQ on feed intake was strongly blocked by the injection of
      bicuculline whereas the effect of muscimol was stimulated by N/OFQ. These results
      suggest that N/OFQ may act at GABA(A) receptors or increases overflow of GABA in
      the brain of chickens to stimulate feeding.

PMID- 16904712
TI  - Dissociation of conditioned and unconditioned factors in the running-induced
      feeding suppression.
AB  - In adult rats, running wheel introduction induces a 7 to 10 day feeding
      suppression, either due to a learned conditioned taste avoidance or to the direct
      unconditioned effects of wheel running. The three experiments investigated the
      effects of wheel introduction on familiar (rat chow) and novel (24% sucrose
      solution) food consumption (Experiment 1), and then explored how alternate-day
      wheel access affected sucrose consumption when it was novel (Experiment 2) or
      familiar (Experiment 3). When paired with wheel introduction the consumption of a
      novel sucrose solution was completely suppressed for an extended period, whether
      the rats had continuous or alternate-day wheel access. In contrast, familiar food
      consumption was suppressed, for a limited period, only on wheel days. When rats
      were pre-exposed to the sucrose, consumption was suppressed only on wheel days.
      The results suggest that in addition to the direct unconditioned effects of wheel
      running on feeding, learning factors may influence the feeding suppression
      observed and thus wheel introduction supports a learned conditioned taste
      avoidance.

PMID- 16904713
TI  - Olfactory enrichment improves the recognition of individual components in
      mixtures.
AB  - Odor mixtures can exhibit synthetic (the mixture is qualitatively different from
      its components) or elemental properties (the components are recognizable). We
      tested how prior olfactory enrichment affects the recognition of individual
      components in binary mixtures. Experimental rats were exposed to pairs of similar
      odors for one-hour periods twice daily over 20 days. Spontaneous discrimination
      between the binary mixture and the individual components of similar pairs of
      odors was tested before and after the odor enrichment. We found that, after the
      enrichment period, rats could discriminate components in binary mixtures that had
      not been discriminated prior to the enrichment period, and that this increase in
      discrimination capability was not always specific to the odorants used during the
      enrichment period.

PMID- 16904714
TI  - Rodney B. Croteau.

PMID- 16904716
TI  - One and a half centuries--a few moments in the evolution of public health.

PMID- 16904717
TI  - Miltefosine--discovery of the antileishmanial activity of phospholipid
      derivatives.
AB  - Miltefosine (hexadecylphosphocholine, Impavidotrade mark), a novel antiprotozoal
      drug used for the treatment of visceral and cutaneous leishmaniasis, was
      identified and evaluated independently in the early 1980s as a potential
      anticancer drug in Germany and as an antileishmanial drug in the UK. Although
      miltefosine is not the most active compound of its class against Leishmania
      parasites in vitro, the early demonstration of activity after oral administration
      in experimental models of visceral leishmaniasis helped to bring this compound to
      the attention of WHO TDR for further development in a unique collaboration model
      with the pharmaceutical industry (Zentaris GmbH). Miltefosine is active against
      most Leishmania species, including those that cause cutaneous disease.

PMID- 16904718
TI  - Different doses of amodiaquine and chloroquine for treatment of uncomplicated
      malaria in children in Guinea-Bissau: implications for future treatment
      recommendations.
AB  - The aim of the present study was to compare different doses of chloroquine (CQ)
      and amodiaquine (AQ) for the treatment of falciparum malaria in children.
      Children with Plasmodium falciparum monoinfection were allocated by block
      randomisation to treatment with CQ 50/kg mg or 25 mg/kg or AQ 15 mg/kg or 30
      mg/kg. The main outcomes were the cumulative adequate clinical and
      parasitological response (ACPR) rates and the number of true recrudescences as
      determined by PCR. A total of 729 children were included. In an evaluability
      analysis, the PCR-uncorrected cumulative ACPR rates on Day 28 for the treatment
      groups CQ 50/kg mg or 25 mg/kg and AQ 15 mg/kg or 30 mg/kg were 90%, 76%, 92% and
      94%, respectively; the PCR-adjusted ACPR rates on Day 28 were 92%, 80%, 94% and
      94%, respectively. No differences in adverse effects were observed. AQ has a high
      cure rate given as 30 mg/kg and 15 mg/kg, although it is not superior to
      treatment with CQ 50 mg/kg. However, 25 mg/kg of CQ is less efficient. As an
      interim option, Guinea-Bissau could change the recommended first-line treatment
      of uncomplicated malaria to CQ 50 mg/kg, reserving AQ as a partner drug for a
      future combination therapy.

PMID- 16904719
TI  - Identify mechanisms of amblyopia in Gabor orientation identification with
      external noise.
AB  - In this study, we applied the external noise method and the PTM model to identify
      mechanisms underlying performance deficits in amblyopia. Amblyopic and normal
      observers performed a Gabor orientation identification task in fovea. White
      external noise was added to the Gabor stimuli. Threshold versus external noise
      contrast (TvC) functions were measured at two performance criterion levels. For a
      subset of observers, we also manipulated the center spatial frequency of the
      Gabor. We found that two independent factors contributed to amblyopic deficits:
      (1) increased additive internal noise, and (2) deficient perceptual templates.
      Whereas increased additive noise underlay performance deficits in all spatial
      frequencies, the degree of perceptual template deterioration increased with the
      center spatial frequency of the Gabor.

PMID- 16904720
TI  - Treatment of high-strength dairy wastewater in an anaerobic deep reservoir:
      analysis of the methanogenic fermentation pathway and the rate-limiting step.
AB  - The wastewater of the largest dairy factory in Israel (Tnuva, Tel-Yosef),
      discharging approximately 6000 tons BOD per year, is treated in two serial, deep
      reservoirs (anaerobic/facultative). In this study, which focused on the anaerobic
      reservoir, we combined in situ measurements (over 18 months) and supporting lab
      experiments, in order to evaluate its efficiency and to identify the rate
      limiting step of the methanogenic fermentation pathway. The anaerobic reservoir
      could remove above 75% of the BOD and COD all year round, but this was not enough
      to prevent malodors during the winter. Acetate and propionate, products of
      lactose fermentation, were the predominant intermediate metabolites in the
      reservoir and their concentrations were strongly dependent on the temperature and
      the organic load. The combined effects of colder winter temperatures and seasonal
      increase of organic load, resulted in a decreased rate of propionate oxidation
      and a consequent accumulation of soluble BOD and COD. Laboratory batch
      experiments, conducted during this season, found propionate oxidation to be the
      rate-limiting step in the process, characterized by a lag period preceding its
      degradation.

PMID- 16904721
TI  - Accumulation and fate of green fluorescent labeled Escherichia coli in laboratory
      scale drinking water biofilters.
AB  - Biological filters combining microbial activity and rapid sand filtration are
      used in drinking water treatment plants for enhanced biodegradable organic
      matters (BOM) removal. Biofilms formed on filter media comprised of bacteria
      enclosed in a polymeric matrix are responsible for the adsorption of BOM and
      attachment of planktonic microorganisms. This study investigated the removal of
      Escherichia coli cells injected into laboratory-scale biofilters and the role of
      biofilm in retaining the injected E. coli. Green fluorescent protein was used as
      a specific marker to detect and quantify E. coli in the biofilms. About 35% of
      the total injected E. coli cells were observed in the filter effluents, when
      initial cell concentrations were measured at 7.4 x 10(6) CFU/mL and 1.6 x 10(7)
      CFU/mL in two separate experiments. The results from real-time PCR and plate
      count analysis indicated that 95% of the E. coli retained inside the filters were
      either non-viable or could not be recovered by colony counting techniques.
      Injected cells were unevenly distributed inside the filter with more than 70%
      located at the top 1/5 of the filter. Images obtained from an epifluorescent
      microscope showed that E. coli cells were embedded inside the biofilm matrix and
      presented mainly as microcolonies intertwined with other microorganisms, which
      was consistent with findings from standard plate count methods and qPCR.

PMID- 16904722
TI  - Degradation of p-nitrophenol in aqueous solution by microwave assisted oxidation
      process through a granular activated carbon fixed bed.
AB  - A microwave (MW) assisted oxidation process was investigated for degradation of p
      nitrophenol (PNP) from aqueous solution. The process consisted of a granular
      activated carbon (GAC) fixed bed reactor, a MW source, solution and air supply
      system, and a heat exchanger. The process was operated in continuous flow mode.
      Air was applied for oxygen supply. GAC acted as a MW energy absorption material
      as well as the catalyst for PNP degradation. MW power, air flow, GAC dose, and
      influent flow proved to be major factors which influenced PNP degradation. The
      results showed that PNP was degraded effectively by this new process. Under a
      given condition (PNP concentration 1330mg/L, MW power 500 W, influent flow 6.4
      mL/min, air flow 100 mL/min), PNP removed 90%, corresponding to 80% of TOC
      removal. The pathway of PNP degradation was deduced based on GC-MS identification
      of course products. PNP experienced sequential oxidation steps and mineralized
      ultimately. Nitro-group of PNP converted to nitrite and nitrate. Biodegradability
      of the solution was improved apparently after treatment by MW assisted oxidation
      process, which benefit to further treatment of the solution using biochemical
      method.

PMID- 16904723
TI  - Enhanced coagulation in a typical North-China water treatment plant.
AB  - The characteristics of typical source waters in northern China and their enhanced
      coagulation features were studied in this paper. Through bench scale tests, a
      composite coagulant (HPAC) was selected for this kind of high alkalinity and pH
      water. It can be 30% more efficient in organic matter (OM) removal than the
      traditional coagulants (AlCl(3), FeCl(3)), and polyaluminum chloride (PACl),
      especially more efficient in removing high SUVA, hydrophobic and high molecular
      weight dissolved organic matter (DOM). It is found that some DOM with low SUVA
      has precedence over that with high SUVA to be removed at conventional dosages in
      some seasons, and that the priority of DOM removal is in the same sequence for
      all the coagulants. DOM with high SUVA is not always more easily removed. When
      applying HPAC as coagulant, flotation process can remove hydrophobic OM more
      efficiently than sedimentation process in pilot scale tests.

PMID- 16904724
TI  - Screening high-fluoride and high-arsenic drinking waters and surveying endemic
      fluorosis and arsenism in Shaanxi province in western China.
AB  - The objectives of this study were to screen high-fluoride and high-arsenic
      drinking waters, to evaluate the effectiveness of fluoride-reducing projects and
      to assess the present condition of endemic fluorosis and arsenism in Shaanxi
      province in western China. For screening high-fluoride drinking waters, five
      water samples were collected from each selected village where dental fluorosis
      patients were detected in 8-12 year-old children. For evaluating the
      effectiveness of fluoride-reducing projects, four water samples were collected
      from each project at end-user level. Fluoride concentrations in water samples
      were measured by fluoride-selective electrode method or spectrophotometry. Dental
      fluorosis in children aging 8-12 years was examined according to Horowitz's Tooth
      Surface Index of Fluorosis. Skeletal fluorosis in adults was detected clinically
      and radiologically according to Chinese Criteria of Clinical Diagnosis of
      Skeletal Fluorosis. For screening high-arsenic waters, 20 water samples were
      collected from each village which was selected from areas characterized by the
      geographic features to induce high-arsenic underground water, i.e., alluvial
      plains, ore mining or smelting areas, geothermal artesians, and thermal springs.
      Arsenic concentrations in water samples were determined by spectrophotometry or
      arsine generation atomic fluorospectrophotometry. Arsenism in adults aging 40-89
      years was examined in villages with arsenic concentrations in drinking water
      above 0.05 mg/l according to Chinese Criteria for Classification of Endemic
      Arsenism Areas and Clinical Diagnoses of Endemic Arsenism. The results showed
      that the fluoride level of 7144 water samples was 1.17 +/- 0.93 mg/l. There were
      3396 (47.6%) high-fluoride waters (fluoride level was above 1.0 mg/l)
      distributing in 786 (45.1%) villages, where about 0.8 million (50.0%) people
      inhabited. Additionally, the 1315 fluoride-reducing projects were studied. The
      fluoride level of the projects was 2.79 +/- 1.09 and 0.98 +/- 0.47 mg/l before
      and after building the projects, which remained at relatively lower level (1.03
      +/- 0.47 mg/l). But there were still 58.0% of the projects providing drinking
      waters with fluoride concentrations beyond 1.0mg/l. The rates of dental fluorosis
      and skeletal fluorosis were 38.2% and 11.8%, respectively. The arsenic level of
      1732 water samples was 0.010 +/- 0.082 mg/l. There were 174 (14.9%) high-arsenic
      waters (arsenic level was above 0.010 mg/l) being detected, distributing in 41
      (38.7%) villages. The arsenic level in 53 (4.5%) water samples was beyond 0.025
      mg/l. There were 3 villages with arsenic level in drinking water beyond Chinese
      National Permissible Limits (0.050 mg/l), and the prevalence rate of arsenism
      reached 37.0% in these three villages, 3.7%, 22.2%, and 11.1% of subjects
      suffering from mild, moderate, and severe arsenism, respectively. Conclusively,
      the wide distribution of high-fluoride drinking waters contributes to the
      prevalence of dental and skeletal fluorosis in Shaanxi province and the quality
      of fluoride-reducing projects should be further improved. Ore mining and smelting
      induces high-arsenic drinking waters, resulting in arsenism prevalence in Shang
      luo city. Proper measures should be taken to deal with water pollution in the ore
      mining and smelting areas in order to solve the high-arsenic water problem in
      Shaanxi province.

PMID- 16904725
TI  - Inhibition of cancer cell growth by cyclin dependent kinase 4 inhibitors
      synthesized based on the structure of fascaplysin.
AB  - Tryptamine derivatives, a new structural class of cyclin dependent kinase 4
      inhibitors, have been identified during extensive biological screening of
      synthetic molecules. The molecules were synthesized based on the structure of
      fascaplysin, which is not only a specific inhibitor of the Cdk4-cyclin D1 enzyme
      but also a relatively toxic molecule, probably because it binds and intercalates
      DNA. Interestingly, the new structural analogues of fascaplysin do not interact
      or intercalate with double-stranded DNA, although they inhibit Cdk4-cyclin D1
      specifically. We found that compound CA199 was the most potent molecule, showing
      at least 25-fold specificity towards Cdk4-cyclin D1 (IC50 for Cdk4-cyclin D1 = 20
      microM, Cdk2 > 500 microM). CA199 inhibits the growth of different cancer cell
      lines at concentrations ranging from 10-40 microM. It blocks growth of
      asynchronous cells at G0/G1 in a retinoblastoma protein (pRb) dependent manner.
      Moreover, CA199 blocks growth only at early G1 in synchronised cells released
      from a mimosine-induced G1/S block. These observations are reminiscent of a true
      Cdk4 inhibitor.

PMID- 16904726
TI  - Mercury conversion processes in Amazon soils evaluated by thermodesorption
      analysis.
AB  - This paper reports on the speciation study and the Hg redox behavior in Amazon
      soils not influenced by gold mining and collected near Manaus, AM, Brazil. The
      samples were incubated by adding Hg(0) and HgCl(2) to dry soil. Solid phase Hg
      speciation analysis was carried out using a Hg thermodesorption technique with
      the aim of distinguishing elemental Hg(0) from Hg(II) binding forms. In the first
      case, we observed the conversion of Hg(0) to Hg(II) binding forms in the range of
      28-68% and a correlation between the percent of oxidation and OM content. Samples
      incubated with Hg(II) showed the formation of Hg(I) and/or Hg(0) in the range of
      19-69%. The lowest values corresponded to the samples with the lowest clay
      contents. The kinetics of conversion of Hg(0) as well as HgCl(2) were roughly
      fitted to the two first order reactions, a fast one and a slow one. It was not
      possible to evaluate differences between sampling sites and types of soils, but
      the mean half-life of the first order reaction obtained by the addition of Hg(II)
      was slower (t(1/2)=365d) than the one obtained by the addition of Hg(0)
      (t(1/2)=148d). Previous studies have shown the predominance of organically bound
      Hg in these samples. Thus, the kinetic difference between Hg oxidation and
      reduction in combination with the efficient retention processes by OM may explain
      the high background values found in Amazon soils.

PMID- 16904727
TI  - Investigation on the adsorption capability of egg shell membrane towards model
      textile dyes.
AB  - Adsorption isotherms of Direct Red 80 (DR80) and Acid Blue 25 (AB25) on the egg
      shell membrane (ESM) were performed at 20+/-1 degrees C. Physical characteristics
      of ESM such as surface area and presence of functional groups were verified. The
      Fourier transform infra-red (FTIR) spectra proved the presence of functional
      groups such as hydroxyl, amine and carbonyl groups in ESM. The surface area of
      ESM was found to be 2.2098 m(2)/g. The effects of operational parameters such as
      initial dye concentration, pH(0), contact time, particle size and ESM doses were
      studied. The Langmuir, Freundlich, BET, Redlich-Peterson and Temkin adsorption
      models were applied to describe the equilibrium isotherms. The pseudo-first-order
      and pseudo-second-order kinetics models were examined to evaluate the kinetics
      data at different pH(0) values (2-12) and the rate constants were calculated.
      Maximum desorption of 81.8% was achieved for both dyes in aqueous solution at
      pH(0) 12. Also scanning electron micrographs (SEM) of the treated and untreated
      adsorbent were performed. Results indicate that ESM could be employed as a
      natural and Eco-Friendly adsorbent material for the removal of trace organics in
      solutions.

PMID- 16904728
TI  - Measurement of bisphenol A concentrations in human colostrum.
AB  - Bisphenol A (BPA), an estrogenic endocrine disrupting chemical, has been reported
      to affect embryos and alter their postnatal development. In the present study, we
      measured the concentrations of BPA in human colostrum by a competitive enzyme
      linked immunosorbent assay (ELISA) with the aim of understanding the present
      status of BPA burden in human breast milk in Shizuoka, Japan. Human colostral
      samples were collected from 101 healthy mothers within three days after delivery.
      The BPA concentrations of colostral samples were estimated by ELISA after the
      acetonitrile extraction and solid phase extraction column purification. BPA in
      101 samples was detected in the concentration range of 1-7 ng ml(-1). The mean
      concentration of BPA was 3.41+/-0.13 (mean+/-SD) ng ml(-1). This is the first
      demonstration as to what BPA concentrations are in human colostrum. The BPA
      concentrations in colostrum were higher than those in blood sera samples obtained
      from healthy women in a previous study. In our study, there was no significant
      correlation between the concentrations of BPA in colostrum and the age and parity
      of mothers.

PMID- 16904729
TI  - Operation of a two-phase partitioning bioreactor for the oxidation of anthracene
      by the enzyme manganese peroxidase.
AB  - A study was conducted to determine the potential of a two-phase partitioning
      bioreactor (TPPB) for the treatment of a poorly soluble compound, anthracene, by
      the enzyme manganese peroxidase (MnP) from the fungus Bjerkandera sp. BOS55.
      Silicone oil was used as the immiscible solvent, which contained anthracene at
      high concentrations. The optimization of the oxidation process was conducted
      taking into account the factors which may directly affect the MnP catalytic cycle
      (the concentration of H(2)O(2) and malonic acid) and those that affect the mass
      transfer of anthracene between the organic and the aqueous phase (solvent and
      agitation speed). The main objective was carried out in terms of improved
      efficiency, i.e., maximizing the anthracene oxidized per unit of enzyme used. The
      TPPB reached nearly complete oxidation of anthracene at a conversion rate of
      1.8mgl(-1)h(-1) in 56h, which suggests the application of enzymatic TPPBs for the
      removal of poorly soluble compounds.

PMID- 16904730
TI  - Dichloroacetic acid degradation employing hydrogen peroxide and UV radiation.
AB  - The degradation reaction of dichloroacetic acid employing H(2)O(2) and UVC
      radiation (253.7nm) has been studied in a well mixed reactor operating inside a
      recycling system. It has been shown that in an aqueous solution no stable
      reaction intermediates are formed and, at every time during the reaction, two
      mols of hydrochloric acid are formed for every mol of dichloroacetic acid that is
      decomposed and, in the same way, there is a paired agreement between the
      calculated TOC concentration corresponding to the unaltered dichloroacetic acid
      and the experimental values measured in the solution. On this basis and classical
      references from the scientific literature for the H(2)O(2) photolysis, a complete
      reaction scheme, apt for reaction kinetics mathematical modeling and ulterior
      scale-up is proposed.

PMID- 16904731
TI  - Species resilience in Pleistocene hominids that traveled far and ate widely: an
      analogy to the wolf-like canids.
AB  - Morphological and genetic analyses have yet to resolve the question of whether
      more than one species of Homo existed contemporaneously in the Pleistocene. In an
      effort to contribute a process-related perspective to hominid phylogenetic
      reconstruction, this paper uses an analogy to the northern wolf-like canids (the
      wolves and coyotes) to ask the question, How many Homo species should there be,
      given their likely behavioral profile(s)? In contrast to earlier comparisons to
      social carnivores which sought to illuminate specific aspects of hominid
      behavioral ecology, this paper explores behavioral constraints on the process of
      speciation itself. The analogy suggests that because Pleistocene Homo probably
      exhibited high habitat tolerance, they would not have had the opportunity to
      speciate, especially in Africa. In contrast to an earlier single-species
      hypothesis based on competitive exclusion between sympatric hominid species, this
      paper explores constraints on the process of speciation under conditions of
      temporary allopatry.

PMID- 16904732
TI  - Organochlorine pesticides in serum and adipose tissue of pregnant women in
      Southern Spain giving birth by cesarean section.
AB  - Since the appearance of DDT, increasingly potent insecticides have been developed
      to overcome the resistance developed by insects to successive products.
      Pesticides are also used in public health programs to control disease vectors.
      Despite legislation to control the use of certain products, they repeatedly
      appear in the adipose tissue, milk and serum of human populations. The present
      study determined the presence of organochlorine molecules in the adipose tissue,
      serum, and umblical cord of women giving birth by cesarean section in order to
      establish a possible correlation in organochlorine molecule content between these
      biological compartments and to examine fetal exposure to molecules with hormonal
      effects. Presence of nine organochlorines was detected by GC/ECD and confirmed by
      GC/MS. Highly significant differences (p<0.000) were observed between adipose
      tissue and maternal serum in concentrations of lindane, HCB, DDE, DDD, and
      endosulfan but not (p>0.5) in concentrations of endosulfan II or endosulfan
      sulfate. Only DDE concentrations differed (p<0.001) between maternal serum and
      umbilical cord serum. An association between pp'DDE and op'DDT was observed in
      maternal serum (p<0.094). An association in pp'DDE and pp'DDD content was found
      between adipose tissue and umbilical cord serum, and in pp'DDT content between
      adipose tissue and maternal serum. Results obtained indicate that exposure can be
      measured solely in serum when relatively high concentrations of pesticides are
      present.

PMID- 16904733
TI  - Analysis of short-term influences of ambient aeroallergens on pediatric asthma
      hospital visits.
AB  - The objective of our study was to investigate the association between daily
      pediatric asthma hospital visits and daily concentrations of aeroallergens and
      their specific species. Records of daily asthma visits in Cincinnati area were
      retrieved from Cincinnati Children's Hospital Medical Center and aeroallergen
      sampling was performed by the Button Inhalable Sampler. The Poisson generalized
      linear model was carried out in which the log of the number of asthma hospital
      visits was related to aeroallergen level, treated as a continuous variable with
      adjustment for seasonal time trend, day of the week, ozone and PM(2.5)
      concentrations, temperature and humidity. The aeroallergens having a significant
      impact on asthma hospital visits were ragweed, oak/maple and Pinaceae pollen.
      Their relative risks on asthma hospital visits with respect to a 100 counts/m(3)
      increase in concentration were in the range of 1.23 to 1.54. The effects in
      causing the asthma exacerbation were delayed by 3 or 5 days.

PMID- 16904734
TI  - Dietary composition and contaminants in north Greenland, in the 1970s and 2004.
AB  - OBJECTIVES: The fatty acid composition and other nutrients in traditional Inuit
      food appear to provide some protection against diseases of affluent
      industrialized societies, such as cardiovascular diseases and type 2 diabetes. A
      transition towards increased amounts of imported food might increase the
      occurrence of these diseases among Inuit. However, since the 1970s it has become
      evident that the marine-based Inuit diet also contains high levels of potentially
      toxic lipophilic organic pollutants and heavy metals. Since these two opposing
      effects on health appear to be inseparable, the phenomenon has become known as
      "The Arctic Dilemma". However, both the fatty acid composition and the
      contaminant levels vary in Greenlandic food items. Thus, in theory, it is
      possible to compose a diet where the benefits outweigh the risks. Our objective
      was to compare traditional and modern meals in Greenland regarding dietary
      composition, content of n-3 fatty acids and contaminants. STUDY DESIGN: The
      present study was part of the Arctic Monitoring and Assessment Programme, AMAP,
      comparing the results of dietary composition and nutrients in 177 traditional
      meals collected in Uummannaq municipality, north Greenland in 1976 with 90 meals
      sampled in Uummannaq town in 2004 under similar conditions. Eleven pesticides, 14
      PCB congeners, heavy metals, selenium, and fatty acids were analysed in meals and
      blood samples from the participants. Contaminant levels were compared between
      1976 and 2004 after adjustment for n-3 fatty acids, indicating local food
      content. RESULTS: Between the traditional meals collected 30 years ago and the
      meals from 2004, dramatic and significant changes have occurred in the dietary
      composition. The percentage of local food has decreased, and with it the intake
      of n-3 fatty acids. Calculated as daily intake, all but three contaminants had
      decreased significantly. However, this could be explained by the lower intake of
      local food. After adjustment for n-3 fatty acid content in the food, significant
      declines of concentration in the local food were evident only for PCBs and lead,
      whereas for mercury, DDTs, and chlordanes the levels were unchanged, and for
      hexachlorobenzene, mirex, and toxaphenes, the levels had increased significantly.
      CONCLUSION: The consumption of locally produced food has decreased in Greenland
      during the last 30 years and this has led to a reduction in the daily intake of
      contaminants. However, the concentrations of contaminants in local food items
      have not decreased, except for PCB and Lead. Therefore, we recommend that the
      consumption of local products is not increased beyond the present level, until
      the level of contaminants is reduced to a safer level.

PMID- 16904736
TI  - Effects of aqueous aluminium on four fish ectoparasites.
AB  - Effects of aqueous aluminium on four species of fish ectoparasites were studied.
      Fish infected by Gyrodactylus derjavini, G. macronychus and Anodonta anatina
      glochidia, and free living Argulus foliaceus were exposed to acidic Al-rich water
      (pH 5.8), acidic Al-poor water (pH 5.8) and control water (pH 6.3). The results
      showed that aqueous aluminium had a negative effect on the ectoparasites tested,
      without any apparent negative effect on the fish hosts. The effect of aluminium
      was dependent on the kind of organism tested. The gyrodactylids were eliminated,
      while the duck mussel glochidia showed a decrease in abundance when exposed to
      200-260 mug Al/l at pH 5.8. The little fish louse showed increased mortality rate
      when exposed to aluminium. The effects of aluminium on the parasites in the
      present study confirm the importance of water quality in general, and
      acidification in particular, for the distribution and population dynamics of
      ectoparasites in freshwater environments.

PMID- 16904735
TI  - DDE-induced apoptosis in children exposed to the DDT metabolite.
AB  - In a preliminary study in children we found a weak positive association between
      the frequency of apoptosis and the exposure to DDT and DDE (a DDT metabolite). In
      order to verify this information, more studies were needed with an increased
      number of children. Thus, the aim of the present work was to see if DDT and its
      metabolites were able to induce apoptosis of PBMC in exposed children. We
      performed a study in children living in three communities located in southern
      Mexico. During the year 2003, we studied a total of 61 healthy children; and
      during the year 2004, 57 children from the same communities were assessed.
      Apoptosis frequencies in PBMC in these children ranged from 0.10% to 8.30% during
      2003 and from 0.12% to 16.20% during 2004, and although we detected exposure to
      DDT, DDD and DDE, significant association with apoptosis frequencies was found
      only with DDE blood levels (p=0.010 and 0.040 for 2003 and 2004 respectively).
      DNA damage and oxidative DNA damage were also studied in 2004 using the comet
      assay. The association between exposure to DDT or DDE and DNA damage was
      significant (p=0.004 and p=0.005 respectively), but the association between DDT
      or DDE and oxidative DNA damage and that of oxidative damage and apoptosis were
      not significant. Taking into account that DDE is the most persistent metabolite,
      it would be important to assess the effects of this DDE-induced apoptosis of PBCM
      in children living in areas where DDT was sprayed.

PMID- 16904737
TI  - Effect of amphetamine on response inhibition in rats showing high or low response
      to novelty.
AB  - Previous work has shown that rats categorized as either high responder (HR) or
      low responder (LR) based on the amount of activity assessed in a novel
      environment show a differential response to stimulant reward, with HR rats self
      administering more amphetamine and cocaine than LR rats. The current study
      assessed behavioral inhibitory processes in HR and LR rats using either fixed
      consecutive number (FCN) or differential reinforcement of low rate of responding
      (DRL) tasks. Individual differences in free-choice preference for a novel
      environment or novel object were also assessed to determine if these measures
      were predictive of performance on these inhibitory tasks. Results showed that,
      regardless of the test used to characterize individual differences in response to
      novelty, groups showed a similar ability to learn the FCN and DRL tasks. When
      subsequently pretreated with amphetamine, there was no significant difference
      between groups in performance efficiency (accuracy) on either the FCN or DRL
      task; however, based on activity in inescapable novelty, HR rats were less
      sensitive than LR rats to amphetamine-disrupted responding on the reinforcement
      lever in the FCN task. Although a deficit in inhibition is generally thought to
      play a role in drug abuse behavior, the differential rate of stimulant self
      administration described previously between HR and LR rats more likely reflects
      an incentive motivational effect that is independent of response inhibition.

PMID- 16904738
TI  - Surface treatments of titanium dental implants for rapid osseointegration.
AB  - The osseointegration rate of titanium dental implants is related to their
      composition and surface roughness. Rough-surfaced implants favor both bone
      anchoring and biomechanical stability. Osteoconductive calcium phosphate coatings
      promote bone healing and apposition, leading to the rapid biological fixation of
      implants. The different methods used for increasing surface roughness or applying
      osteoconductive coatings to titanium dental implants are reviewed. Surface
      treatments, such as titanium plasma-spraying, grit-blasting, acid-etching,
      anodization or calcium phosphate coatings, and their corresponding surface
      morphologies and properties are described. Most of these surfaces are
      commercially available and have proven clinical efficacy (>95% over 5 years). The
      precise role of surface chemistry and topography on the early events in dental
      implant osseointegration remain poorly understood. In addition, comparative
      clinical studies with different implant surfaces are rarely performed. The future
      of dental implantology should aim to develop surfaces with controlled and
      standardized topography or chemistry. This approach will be the only way to
      understand the interactions between proteins, cells and tissues, and implant
      surfaces. The local release of bone stimulating or resorptive drugs in the peri
      implant region may also respond to difficult clinical situations with poor bone
      quality and quantity. These therapeutic strategies should ultimately enhance the
      osseointegration process of dental implants for their immediate loading and long
      term success.

PMID- 16904739
TI  - Application of laser ablation ICPMS to trace the environmental history of chum
      salmon Oncorhynchus keta.
AB  - Trace element levels in otoliths of chum salmon Oncorhynchus keta were examined
      by means of laser ablation inductively coupled plasma mass spectrometry (LA
      ICPMS). A close linear relationship in the Sr:Ca ratios between EPMA (X-ray
      analysis with an electron microprobe) and LA-ICPMS analyses was found (p<0.0001),
      suggesting that the latter technique could be used to separate the marine and
      freshwater life phases. Mg:Ca, Cr:Ca, Zn:Ca and Ba:Ca ratios in either the core
      region or the oceanic growth zone of the otoliths varied among sites. These
      differences suggest that elemental compositions may reflect environmental
      variability among spawning (breeding) or habitat sites. Thus, those element
      ratios demonstrate the potential to be used to distinguish between fish spawning
      (breeding) sites and habitats for this species of salmon.

PMID- 16904740
TI  - Proliferation and osteoblastic differentiation of human bone marrow-derived
      stromal cells on akermanite-bioactive ceramics.
AB  - In the present study, the effects of a calcium magnesium silicate bioactive
      ceramic (akermanite) on proliferation and osteoblastic differentiation of human
      bone marrow stromal cells (hBMSC) have been investigated and compared with the
      classical ceramic (beta-tricalcium phosphate, beta-TCP). Akermanite and beta-TCP
      disks were seeded with hBMSC and kept in growth medium or osteogenic medium for
      10 days. Proliferation and osteoblastic differentiation were evaluated on day 1,
      4, 7 and 10. The data from the Alamar Blue assay and lactic acid production assay
      showed that hBMSC proliferated more significantly on akermanite than on beta-TCP.
      The analysis of osteoblast-related genes, including alkaline phosphatase (ALP),
      osteopontin (OPN), bone sialoprotein (BSP) and osteocalcin (OC), indicated that
      akermanite ceramics enhanced the expression of osteoblast-related genes, but type
      I collagen (COL I) showed no noticeable difference among akermanite and beta-TCP
      ceramics. Furthermore, this stimulatory effect was observed not only in
      osteogenic medium, but also in normal growth medium without osteogenic reagents
      such as l-ascorbic acid, glycerophosphate and dexamethasone. This result suggests
      that akermanite can promote osteoblastic differentiation of hBMSC in vitro even
      without osteogenic reagents, and may be used as a bioactive material for bone
      regeneration and tissue engineering applications.

PMID- 16904741
TI  - Soluble factors from LPS- and PHA-activated PBMC induce MAPK, Stat1 and Stat3
      phosphorylation in primary cultures of human term placental trophoblasts:
      implications for infection and prematurity.
AB  - Infection of the maternal vaginal tract is one of the single most important
      antecedents of premature labor. We have hypothesized that the abundant local
      synthesis of pro-inflammatory cytokines that occurs during infection may disrupt
      the delicate "immunological cross-talk" that must occur between maternal and
      fetal tissues in order to carry pregnancy to term. These experiments were
      undertaken as part of a larger study directed at testing that hypothesis. We
      prepared primary cultures of human trophoblasts from term placentas. Cell
      cultures were stimulated with conditioned medium from resting, PHA or LPS
      activated peripheral blood mononuclear cells (PBMC). Medium with LPS or PHA at
      the same concentration as that used to stimulate the PBMC was used as an
      additional control. Lysates were subjected to western blotting for activated
      forms of the mitogen-activated protein kinases (MAPK), Stat1, and Stat3. Western
      blotting showed phosphorylation of the Jun kinase (JNK), p38, and Erk1/Erk2 MAPK
      in trophoblasts incubated with conditioned medium from LPS or PHA-activated PBMC
      but not from medium from resting PBMC, or with PHA or LPS alone. Phosphorylation
      could be detected as early as 5 min and was still observable by 10 min, the
      latest time point tested. Similarly, Stat1 and Stat3 phosphorylation was observed
      within 10 min of exposure to conditioned medium and was still observable 10 min
      after exposure. Immunohistochemistry also demonstrated nuclear translocation of
      both Stat1 and Stat3 after stimulation of trophoblasts with medium from activated
      PBMC. These findings are compatible with the hypothesis that immunologic balance
      at the maternal-fetal interface is maintained by ongoing "cross-talk" between the
      fetus (and fetally-derived tissues) and the maternal immune system. Infection of
      the maternal vaginal tract may disrupt this delicate immunologic balance,
      initiating inflammatory events that ultimately result in preterm labor.

PMID- 16904742
TI  - L-serine uptake by human placental microvillous membrane vesicles.
AB  - The human fetus requires more glycine than any other amino acid but placental
      glycine transfer to the fetus is insufficient to meet fetal demand. L-Serine
      could represent a major metabolic source of glycine for the human fetus but
      little is known about the kinetics and physiology of L-serine uptake by the human
      placenta. We have characterised the amino acid transport systems involved in the
      uptake of L-serine by the microvillous membrane of the human placental
      syncytiotrophoblast and compared the uptake rates to those of glycine. L-Serine
      uptake into microvillous membrane (MVM) vesicles was primarily mediated by system
      A (MeAIB inhibitable) and system L (BCH inhibitable). Further characterisation
      using specific substrates of LAT1 and LAT2 found the pattern of L-serine uptake
      was consistent with that expected for uptake mediated by LAT2. Uptakes were
      performed with tracer levels of (14)C-L-serine, physiological levels of L-serine,
      or with physiological levels of amino acids. As amino acid concentrations rose,
      the proportion of uptake by System L decreased while uptake by uncharacterised
      Na(+)-independent systems increased. Uptake of Lserine into MVM vesicles had a
      V(max) of 2.1+/-0.4 nmol/mg protein/min, which was significantly higher than for
      glycine (V(max) 1.0+/-0.2 nmol/mg protein/min). This indicates that MVM vesicles
      have a higher uptake capacity for L-serine than glycine, despite a greater demand
      for glycine over serine for fetal protein synthesis. Further studies are now
      required to define the fate of L-serine taken up by the placenta and its
      importance for the fetus.

PMID- 16904743
TI  - Bipotential cytotrophoblasts in the first trimester of pregnancy?: comment on
      Baczyk et Al., published in issue 27.

PMID- 16904744
TI  - Ameliorative effects of vitamin supplementation on ethyl methane sulphonate
      induced genotoxicity in a fish, Anabas testudineus.
AB  - The efficacy of 0.02% vitamin C (VC; l-ascorbic acid) and 0.05% beta-carotene
      (BC) at the rate of 1 ml/100g of body weight in amelioration of ethyl methane
      sulphonate (EMS)-induced genotoxicity has been studied in an Indian endemic fish,
      Anabas testudineus by using several cytogenetical endpoints like chromosome
      aberrations, micronuclei (MN) and abnormal nuclei (AN), and sperm head anomaly at
      6, 24, 48, 72 and 96 h after treatment, as compared to suitable controls
      (distilled water (DW)-treated control for EMS and VC-treated fish, and 1% alcohol
      treated control for BC-treated fish). Both VC and BC reduced EMS-induced
      genotoxicity at all the fixation intervals as compared to their respective
      controls. Additionally, effects of two more doses of VC (0.01% and 0.05%) and BC
      (0.02% and 0.1%) were analyzed at 72 h after treatment (at the peak period of EMS
      genotoxicity) for testing their relative efficacy in amelioration of EMS-induced
      cytogenetical damage in this fish. All the three doses of both VC and BC appeared
      to reduce the EMS-induced genotoxicity in this fish to a variable extent, of
      which the higher dose of VC appeared to give marginally better protection while
      the dose-response relationship was inconclusive for BC. The results of this study
      can lead to future research for exploring if low doses of these vitamins may be
      useful in protecting fish from genotoxic damage on exposure to mutagenic agents
      in small confined/stagnant waters.

PMID- 16904745
TI  - Imaging human EEG dynamics using independent component analysis.
AB  - This review discusses the theory and practical application of independent
      component analysis (ICA) to multi-channel EEG data. We use examples from an
      audiovisual attention-shifting task performed by young and old subjects to
      illustrate the power of ICA to resolve subtle differences between evoked
      responses in the two age groups. Preliminary analysis of these data using ICA
      suggests a loss of task specificity in independent component (IC) processes in
      frontal and somatomotor cortex during post-response periods in older as compared
      to younger subjects, trends not detected during examination of scalp-channel
      event-related potential (ERP) averages. We discuss possible approaches to
      component clustering across subjects and new ways to visualize mean and trial-by
      trial variations in the data, including ERP-image plots of dynamics within and
      across trials as well as plots of event-related spectral perturbations in
      component power, phase locking, and coherence. We believe that widespread
      application of these and related analysis methods should bring EEG once again to
      the forefront of brain imaging, merging its high time and frequency resolution
      with enhanced cm-scale spatial resolution of its cortical sources.

PMID- 16904746
TI  - Cognitive and neural plasticity in aging: general and task-specific limitations.
AB  - There is evidence for cognitive as well as neural plasticity across the adult
      life span, although aging is associated with certain constraints on plasticity.
      In the current paper, we argue that the age-related reduction in cognitive
      plasticity may be due to (a) deficits in general processing resources, and (b)
      failure to engage in task-relevant cognitive operations. Memory-training research
      suggests that age-related processing deficits (e.g., executive functions, speed)
      hinder older adults from utilizing mnemonic techniques as efficiently as the
      young, and that this age difference is reflected by diminished frontal activity
      during mnemonic use. Additional constraints on memory plasticity in old age are
      related to difficulties that are specific to the task, such as creating visual
      images, as well as in binding together the information to be remembered. These
      deficiencies are paralleled by reduced activity in occipito-parietal and medial
      temporal regions, respectively. Future attempts to optimize intervention-related
      gains in old age should consider targeting both general processing and task
      specific origins of age-associated reductions in cognitive plasticity.

PMID- 16904747
TI  - Disputed discovery: vivisection and experiment in the 19th century.
AB  - In the early 19th century, physiologists Sir Charles Bell and Francois Magendie
      both claimed to have been the first to identify separate motor and sensory nerve
      roots, a discovery acknowledged by their contemporaries as one of the most
      important of the age. This priority dispute came to embody distinct visions of
      physiology, and of the role of experimentation and vivisection within that
      discipline. The dispute remained unresolved, in part, because of competing
      definitions of what was being discovered.

PMID- 16904748
TI  - Brighty, donkeys and conservation in the Grand Canyon.
AB  - The Grand Canyon is a vast place. It is almost incomprehensible in size. And yet
      it can also seem strangely crowded. Millions of tourists flock to the Grand
      Canyon in northern Arizona every year. In 1999, almost 5 million people visited,
      the highest figure in Canyon history. And each one of them expected to see a
      wild, free and untrammelled landscape. Despite the obvious natural resources,
      this expectation has proved anything but easy to satisfy. The US National Park
      Service (NPS), responsible for the management of most large North American parks
      (along with several historic sites and museums), has struggled to make or keep
      the canyon "grand". Park rangers have grappled with a multitude of issues during
      the past century, including automobile congestion, drying of the Colorado River
      and uranium mining inside the park. Conservation has posed a unique set of
      challenges. On a fundamental level, "restoring" the Grand Canyon to its
      "original" wilderness setting has proved intensely problematic. In the field of
      wildlife management, restoring the Canyon to its pre-Columbian splendour has
      entailed some tough decisions--none more so than a 1976 plan to eliminate a
      sizeable population of feral burros (wild donkeys) roaming the preserve, animals
      classified as exotics by the NPS.

PMID- 16904749
TI  - The prevalence of cognitive malingering in persons reporting exposure to
      occupational and environmental substances.
AB  - OBJECTIVE: Directly estimate the prevalence of cognitive malingering in persons
      claiming exposure to occupational and environmental substances. METHODS:
      Retrospective review of 128 neuropsychological cases with financial incentive.
      Estimates were based on two methods: (1) clinical identification using the Slick,
      Sherman and Iverson criteria for malingered neurocognitive dysfunction (MND), and
      (2) statistical modeling based on patient performance on several individual
      psychometric indicators of malingering. RESULTS: The prevalence based on the
      clinical method was 40%. The statistically based estimates ranged from 30% to
      more than 45% depending on model parameters. Different incentive parameters may
      influence prevalence. CONCLUSIONS: Cognitive malingering in toxic exposure is
      common and must be adequately addressed in the clinical neuropsychological
      assessment of toxic exposure and in research on its neurocognitive effects or
      findings will likely over-estimate the degree of cognitive impairment and related
      disability.

PMID- 16904751
TI  - Determination of uranine tracer dye from underground water of Mecsek Hill,
      Hungary.
AB  - The underground water system of Mecsek Hill, Hungary was studied using
      spectrofluorometry. A quantitative dye-tracing technique was used to map the
      connections between ground water recharge points and the springs and wells.
      Excitation-emission matrices were used to establish optimal spectroscopic
      parameters for spectral measurements. Only an EEM gives full spectrofluorimetric
      information about the sample and makes possible the determination of the optimal
      wavelength parameters. The uranine concentration was determined by measuring the
      synchronous excitation spectra of water samples. It was found that under the 4
      microg/L uranine concentration, no special chemical treatment was necessary if
      the pH values remained between 7 and 8. However, above this concentration, the
      solution should be diluted to avoid spectral distortion from the increasing
      absorbance of the sample. Long-term concentration measurements were conducted
      based on spectrofluorometry.

PMID- 16904752
TI  - Evaluating the clinical significance of responses by psychiatric inpatients to
      the mental health subscales of the SF-36.
AB  - BACKGROUND: The Mental Health subscales of the Medical Outcomes Short Form
      Questionnaire (SF-36; [Ware, J.E., Snow, K.K., Kosinski, M., Gandek, B., 1993. SF
      36 Health Survey: Manual and Interpretation Guide. Boston: The Health Institute,
      New England Medical Center]) are increasingly being used to evaluate treatment
      outcomes, but data to assess the clinical significance of changes are absent. The
      present study applied Jacobson and Truax's [Jacobson, N.S., Truax, P. 1991.
      CLINICAL SIGNIFICANCE: a statistical approach to defining meaningful change in
      psychotherapy research. Journal of Consulting and Clinical Psychology 59, 12-19]
      criteria for clinical significance to the mental health items of the SF-36.
      METHOD: Admission and discharge data were collated from 1830 consecutive
      inpatients at a psychiatric hospital, using the SF-36, the Depression Anxiety
      Stress Scale, the Quality of Life Enjoyment and Satisfaction Questionnaire and
      the clinician-rated Health of the Nation Outcome Scale. RESULTS: Appropriate
      improvement cut-off scores for the mental health subscales of the SF-36 are
      reported, and significant differences were found between outcome groups according
      to clinically significant improvement. LIMITATIONS: CLINICAL SIGNIFICANCE as a
      means of assessing outcome should be used with caution in inpatient settings, as
      further improvement is often expected upon discharge from the hospital.
      CONCLUSIONS: Assessing clinically significant improvement is an effective means
      of measuring treatment outcome in terms of quality of life and symptom
      improvement in psychiatric care.

PMID- 16904753
TI  - Cloning of a gene fragment encoding bovine complement component C3d with
      expression and characterization of derived fusion proteins.
AB  - The gene fragment coding for bovine C3d gene (boC3d) was cloned and expressed as
      a component of fusion proteins destined for use in vaccine studies in cattle, and
      for in vitro experiments. This fragment of complement protein C3 (C3d) has been
      shown to enhance B cell responses when complexed with antigen. Three potential
      vaccine constructs were engineered to contain one, two or three boC3d units
      linked to a fragment of the leukotoxin of Mannheimia haemolytica A1, an
      economically important pathogen of cattle that causes a fibrinous pneumonia in
      calves. A recombinant biotinylated boC3d protein (for use in in vitro studies)
      was generated by endogenous biotinylation in Escherichia coli by means of the
      BirA holoenzyme synthetase. All recombinant proteins incorporated polyhistidine
      tags and were purified by nickel-agarose chromatography, then analyzed by SDS
      PAGE and Western immunoblot. The identity of boC3d was confirmed by mass
      spectrometry, since monoclonal antibodies to boC3d were not available. To date,
      published research into the adjuvant activities of C3d has been limited to
      experiments in mice and rabbits, using antigens unrelated to diseases occurring
      naturally in these species. The boC3d fusion proteins expressed in this study
      will provide the basis for immunization trials in cattle and studies of receptor
      binding and cell activation of bovine lymphocytes.

PMID- 16904754
TI  - The effect of tuberculin testing on the development of cell-mediated immune
      responses during Mycobacterium bovis infection.
AB  - Protection against tuberculosis (TB) is associated with Th1-type cell-mediated
      immunity (CMI). Whilst the intradermal injection of partially purified
      derivatives of tuberculin (PPD) represents the classic test assessing the delayed
      type hypersensitivity (DTH) response used in both humans and cattle for
      diagnosing TB, it has been suggested that the test may modulate host CMI
      responses. To investigate the kinetics of the development of the DTH response and
      its subsequent effect on CMI responses, groups of 6-month old calves were
      inoculated intranasally with 8 x 10(4) cfu of Mycobacterium bovis, subjected to
      the comparative intradermal tuberculin test (TT) using bovine and avian PPD (PPD
      B, PPD-A) at various time intervals post-infection, and immune responses
      compared. These included DTH, lymphocyte proliferation, IgG production, and
      synthesis of the cytokines: IFNgamma, IL-10, IL-4, IL-6, and IL-13. All animals
      were subjected to post-mortem examination. The kinetics of the development of the
      DTH response assessed in the TT was such that infected cattle could be identified
      as early as 3 weeks post-infection, which correlated with the detection of an
      antigen-specific IFNgamma response. Transient increases in plasma-derived
      IFNgamma as a result of TT during an established TB infection were more
      pronounced when blood was stimulated with PPD-A compared with PPD-B stimulation.
      This has the potential to mask diagnosis of infection as a result of the stronger
      avian-bias if the IFNgamma test is used the week following TT. Disease pathology
      was not affected by TT. A transient failure to a second TT was observed in 1 of
      30 animals and the time (post-infection) at which the TT is administered may be
      of significance. In serum, IgG responses to PPD-B, which were undetectable prior
      to TT, were elevated after TT and were most pronounced in cattle that were TT at
      6 weeks post-infection. Other cytokines were also affected by the TT; IL-4 mRNA
      levels increased and IL-6 mRNA levels decreased, whilst PPD-B specific IL-10
      protein synthesis was enhanced. These observations may offer the potential for
      further diagnostic assays that could complement the TT and IFNgamma test.

PMID- 16904750
TI  - Synaptic plasticity and phosphorylation.
AB  - A number of neuronal functions, including synaptic plasticity, depend on proper
      regulation of synaptic proteins, many of which can be rapidly regulated by
      phosphorylation. Neuronal activity controls the function of these synaptic
      proteins by exquisitely regulating the balance of various protein kinase and
      protein phosphatase activity. Recent understanding of synaptic plasticity
      mechanisms underscores important roles that these synaptic phosphoproteins play
      in regulating both pre- and post-synaptic functions. This review will focus on
      key postsynaptic phosphoproteins that have been implicated to play a role in
      synaptic plasticity.

PMID- 16904755
TI  - Generation of canine dendritic cells from peripheral blood monocytes without
      using purified cytokines.
AB  - Dendritic cells (DCs), which differentiate in vitro from peripheral blood
      monocytes (PBMOs) or bone marrow precursors, are a promising candidate for
      immunotherapy against cancer. The dog, which suffers common types of cancers
      along with humans, make an ideal large animal model for cancer studies. Monocyte
      derived DCs in the dog have not been well characterized, however, since the
      appropriate condition for in vitro differentiation has not been established. To
      tackle this problem, we have developed a conditioned media by culturing T cells
      with immobilized anti-canine CD3 antibody, and sought to induce differentiation
      of DCs from PBMOs. When purified CD14+ PBMOs were cultured in the presence of 25%
      T cell conditioned medium (TCCM), the PBMOs increased size and had extended
      dendritic processes by day 12 of the culture. The cultured PBMOs were found to
      increase the expression of MHC class II and CD1a molecules, and significantly
      increased stimulatory activity for allogeneic T cells in the mixed leukocyte
      reaction. Moreover, the cells significantly increased their expression of IL-18
      and IFN-gamma when stimulated with polyinosinic-polycytidylic acid (Poly (I:C)).
      The cells have a reduced phagocytic activity, which is a common defect in mature
      DCs. It follows from these results that TCCM does induce the differentiation of
      DCs from PBMOs.

PMID- 16904757
TI  - Persistence of CD16+/CD56-/2B4+ natural killer cells: a highly dysfunctional NK
      subset expanded in ocular myasthenia gravis.
AB  - We report a case of myasthenia gravis associated with marked expansion of an
      unusual CD16(+)CD56(-)2B4(+) NK subset. These atypical cells were characterized
      by poor cytotoxicity against CD48(+) target cells and high proliferation due to
      2B4/CD48 interaction. IL18, IFN-gamma and TGF-beta levels were profoundly
      different in this patient than in healthy donors. Immunosuppressive treatment
      induced disease remission and decreased the CD16(+)CD56(-)2B4(+)NK cells count.
      Our data suggest that expansion of this NK subset in myasthenia gravis patients
      may account for the deleterious NK cell functioning that occurs in this
      autoimmune disease.

PMID- 16904756
TI  - Rituximab reduces B cells and T cells in cerebrospinal fluid of multiple
      sclerosis patients.
AB  - Effects of B cell depletion by rituximab, a monoclonal antibody to CD20, were
      studied in patients with relapsing MS that had not responded optimally to
      standard immunomodulatory therapies. Flow cytometry demonstrated reduced
      cerebrospinal fluid (CSF) B cells and T cells in most patients at 6 months post
      treatment. ELISAs demonstrated modest reductions in serum antibodies to myelin
      oligodendrocyte glycoprotein and myelin basic protein in some subjects. Beta
      interferon neutralizing antibodies were reduced in three subjects, but developed
      anew after treatment in three others, suggesting caution in considering rituximab
      as a means to eliminate NABs. In summary, rituximab depleted B cells from CSF at
      24 weeks after initial treatment, and this B cell depletion was associated with a
      reduction in CSF T cells as well.

PMID- 16904758
TI  - Severe acute middle ear infections: microbiology and treatment.
AB  - OBJECTIVE: The database at the ENT-Department, Aarhus University Hospital
      describing the specific local flora of acute otitis media (AOM) and acute
      mastoiditis (AM) in Aarhus County has become the key element in securing a
      rational and specific antibiotic treatment. We present our data concerning AOM,
      mastoidismus and AM. Our purpose is to determine (I) clinical presentation, (II)
      causative pathogens, (III) resistance patterns, (IV) type of antibiotic
      treatment, and (V) accuracy of the antibiotic treatment. METHODS: Patients under
      the age of 18 years, treated for AOM with extensive affected well-being and AM,
      at the ENT-Department, Aarhus University Hospital during 3 years from January
      2001 to December 2003. RESULTS: A total of 106 patients were identified. Sixty
      seven patients with AOM and 39 patients with AM. The overall bacterial flora
      found is dominated by S. pneumococci all 100% susceptible to penicillin. However,
      Staphylococcus aureus is the primary bacterial pathogens cultured from patients
      treated with preadmission antibiotics. CONCLUSION: If a specimen from an AOM
      patient is obtained after the initiation of antibiotic treatment one should
      consider the possibility of the culture found being a result of the initial led
      treatment and not the causative AOM pathogen. Our data suggest that a restricted
      use of antibiotics in children with AOM may be associated with a higher incidence
      of acute mastoiditis. Significant higher leucocytes count and CRP are found in
      the acute mastoiditis group compared to the AOM group.

PMID- 16904759
TI  - Surgical resection of type III juvenile angiofibroma without preoperative
      embolization.
AB  - OBJECTIVES/HYPOTHESIS: To evaluate the outcome of surgical resection of type III
      juvenile angiofibroma without preoperative embolizationo in 20 young male
      patients. PATIENTS AND METHODS: Twenty young male patients with type III JAF
      (based on Fisch classification by CT/MRI or both), were operated on by endoscopic
      assisted midfacial degloving approach without preoperative embolization. The
      surgical technique is described in details. RESULTS: Apart from a case developed
      cerebrospinal fluid rhinorrhea (CSF) intraoperatively there were neither major
      operative nor postoperative complications. CSF leak was repaired through the same
      approach successfully in the same set. Eighteen patients had complete tumor
      clearance with no residual or recurrence during the follow up period which ranged
      from 6 months to 10 years. Recurrence was detected early by endoscopic
      examination in two cases (3 and 8 months postoperatively) and confirmed by CT and
      MRI. Endoscopic transnasal removal of the recurrent JAF was done successfully
      under local anesthesia in the first patient and under general anesthesia in the
      second with no recurrence during the follow up period. CONCLUSIONS: Surgical
      resection of stage III JAF without embolization through endoscopic assisted
      midfacial degloving approach can be used as an adequate surgical technique with
      acceptable intraoperative blood loss and low rate of recurrence.

PMID- 16904760
TI  - Arousal and reward: a dichotomy in orexin function.
AB  - The orexins (or hypocretins) are neuropeptide transmitters made exclusively in
      hypothalamic neurons that have extensive CNS projections. Previous studies
      reported that this system is most strongly associated with feeding, arousal and
      the maintenance of waking. We review here recent studies that reveal a novel and
      important role for the orexin/hypocretin neuronal system in reward processing and
      addiction. We propose that the current evidence indicates a dichotomy in orexin
      function, such that orexin neurons in the lateral hypothalamus regulate reward
      processing for both food and abused drugs, whereas those in the perifornical and
      dorsomedial hypothalamus regulate arousal and response to stress. Evidence also
      indicates roles for lateral hypothalamus orexin neurons and ventral tegmental
      orexin receptors in reward-based learning and memory.

PMID- 16904761
TI  - Odortypes and MHC peptides: Complementary chemosignals of MHC haplotype?
AB  - The olfactory and immune systems must perform optimally in the task of
      recognizing thousands of molecules to ensure survival. A particularly intriguing
      link between these systems is that animals can smell differences in the major
      histocompatibility complex (MHC), a cluster of highly polymorphic genes found on
      human chromosome 6 and mouse chromosome 17. Two different sets of compounds found
      in urine have been postulated to convey information on MHC haplotype: volatile
      compounds (odortypes) and MHC peptides. Here we argue for complementary roles for
      these chemosignals.

PMID- 16904762
TI  - A cell-based luminescence assay is effective for high-throughput screening of
      potential influenza antivirals.
AB  - The spread of highly pathogenic avian influenza across geographical and species
      barriers underscores the increasing need for novel antivirals to compliment
      vaccination and existing antiviral therapies. Identification of new antiviral
      lead compounds depends on robust primary assays for high-throughput screening
      (HTS) of large compound libraries. We have developed a cell-based screen for
      potential influenza antivirals that measures the cytopathic effect (CPE) induced
      by influenza virus (A/Udorn/72, H3N2) infection in Madin Darby canine kidney
      (MDCK) cells using the luminescent-based CellTiter Glo system. This 72 h assay is
      validated for HTS in 384-well plates and performs more consistently and reliably
      than methods using neutral red, with Z values>0.8, signal-to-background>30 and
      signal-to-noise>10. In a blinded pilot screen (n=10,781) at 10 microM
      concentration, four compounds (with previously demonstrated efficacy against
      influenza) inhibited viral-induced CPE by >50%, with EC50/CC50 values comparable
      to those determined by other cell-based assays, thereby validating this assay
      accuracy and ability to simultaneously evaluate compound cellular availability
      and/or toxicity. This assay is translatable for screening against other influenza
      strains, such as avian flu, and may facilitate identification of antivirals for
      other viruses that induce CPE, such as West Nile or Dengue.

PMID- 16904763
TI  - Chronobiological disturbances with hyperthermia and hypercortisolism induced by
      chronic mild stress in rats.
AB  - The chronic mild stress (CMS) model has been established as a realistic model of
      depressive disorder as it simulates anhedonia. In the present study, the
      consumption of sucrose solution was decreased in the rats exposed to CMS, which
      coincided with many published studies. Since depression is a multifaceted
      disorder, and a number of symptoms may be present, including circadian rhythm
      disturbances, we attempted to find the chronobiological abnormalities in CMS
      rats. After 4-week of the stress procedure, the rhythmic pattern of rectal
      temperature in the CMS group was extinguished. In particular, the temperature in
      the CMS group in the light phase was significantly higher than that in the
      control group. The plasma corticosterone levels in the CMS group were remarkably
      increased in the light phase compared to the control group, but not in the dark
      phase. It was concluded that the CMS procedure caused the disturbance of
      circadian rhythms with hyperthermia and hypercortisolism.

PMID- 16904764
TI  - Long-term monitoring of the health status of female perch (Perca fluviatilis) in
      the Baltic Sea shows decreased gonad weight and increased hepatic EROD activity.
AB  - Annual investigations of the health status of female perch (Perca fluviatilis)
      were performed during 8-13 years in order to detect long-term, large-scale
      changes in the Baltic Sea. These background data are also meant to be used as
      baselines in recipient investigations at various point sources in the Baltic Sea.
      Fish were sampled at three coastal sites in Sweden: two in the Baltic Proper
      (since 1988) and one in the Bothnian Bay (since 1993). In all, 19 biochemical,
      physiological and histopathological variables were measured. By reflecting
      central functions of life, such as red blood cell functions, immune defence,
      liver function, biotransformation processes, intermediary metabolism, ion
      balance, and reproduction, the selected variables give a good picture of the
      health status of the fish. The most important observations were strong trends
      towards decreased gonadosomatic index (relative gonad size) and increased hepatic
      EROD activity in female perch in the Baltic Proper. Most of the other variables
      varied little between the years. The reduced gonad size and the EROD induction
      indicate that factors in the environment, e.g. the occurrence of pollutants,
      affect important physiological functions, such as reproduction and
      biotransformation processes, in fish even in a reference area in the Baltic
      Proper. It is urgent to make further studies in order to identify which
      pollutant(s) or other possible cause(s) are responsible for the observed
      biological effects.

PMID- 16904765
TI  - ERM proteins in epithelial cell organization and functions.
AB  - ERM (Ezrin, Radixin, Moesin) proteins are membrane-cytoskeleton linkers that
      regulate the structure and the function of specific domains of the plasma
      membrane. ERM proteins are expressed in all metazoan analyzed so far. Genetic
      analysis of ERM protein functions has recently been performed simultaneously in
      three different organisms, mouse, Drosophila melanogaster and C. elegans. These
      studies have revealed a remarkable conservation of the protein functions through
      evolution. Moreover they have shed light on the crucial role these proteins play
      in various physiological processes that occur in epithelial cells.

PMID- 16904766
TI  - Aging in Italy: urban-rural differences.
AB  - Urban and rural living environments play a key role in social gerontology. The
      aim of this paper is to examine urban-rural differences in Italy against some
      influencing key factors as well as to analyse whether these differences can be
      explained by the environmental setting or the age and, in some cases, the
      education of its elderly population. The study is based on data collected from
      the European funded MOBILATE 2000 project, which was carried out in Finland, The
      Netherlands, Hungary, Germany, and Italy. The Italian sample (600 subjects) was
      divided into rural and urban areas, and stratified according to gender and age.
      Older people living in rural areas were always significantly less well educated
      than those in urban areas. The average rural household size was larger than its
      urban counterpart. In general, Italian elderly people living in rural areas were
      less likely to live alone than their European peers. The social network was
      usually located close to the respondents' houses. Investigation of leisure
      activities and the use of new technologies revealed that elderly urban dwellers
      were not only more active than their rural peers, but also more technologically
      minded. A regression analysis (R(2)=0.551) of the number of new technologies used
      by subjects, yielded living area, age, years of education (the strongest
      explanatory variable), and number of leisure activities performed as predictors.

PMID- 16904767
TI  - Cardio-cerebrovascular complications in elderly with diabetes.
AB  - Authors have considered the prevalence of hypertension (HT), myocardial
      infarction (MI) and stroke (S), in elderly subjects with diabetes, impaired
      fasting glucose (IFG) and normal fasting glucose (NFG), respectively. A high
      occurrence of diabetes in elderly subjects has been found. MI and S were more
      frequent in diabetic group than in IFG and NFG ones. HT proved to be elevated in
      the total pool, especially in older olds, and with a higher prevalence among
      those with diabetes. A 5-year follow-up has been carried out. The index of
      survival for MI and S was lower in subjects with diabetes. The subjects affected
      by both MI and S displayed the worst index of survival in all the three
      categories considered, therefore, it can be stated that such an association is a
      determinant factor of mortality.

PMID- 16904768
TI  - 64-multislice computed tomography in consecutive patients with suspected or
      proven coronary artery disease: initial single center experience.
AB  - BACKGROUND: The improved accuracy of 64-multislice CT (MSCT) suggests that this
      technique may replace other non-invasive methods to detect clinically significant
      coronary atherosclerosis. The aim of the present study was to assess the clinical
      usefulness of in consecutive patients with suspected or proven coronary artery
      disease (CAD). METHODS: 64-MSCT was performed in 56 patients (age 56+/-16 years,
      50 male) with suspected or proven CAD (35 patients with chest pain/positive
      provocative tests/risk factors), 18 with documented significant CAD, CABG surgery
      or stent implantation, 3 non-assessable with selective angiography because of
      peripheral vascular disease or large aneurysms of the ascending aorta. RESULTS:
      One patient was excluded because of contrast extravasation. In 30/55 patients
      (54%) 64-MSCT excluded significant coronary stenoses; in 13/55 patients (24%)
      angiography and/or angioplasty were recommended to treat (3) 50% diameter
      stenoses shown by MSCT, a diagnosis confirmed in 9 (81.8%) of the 11 patients who
      underwent further investigations; 12/55 patients (22%) needed angiography or
      other preliminary non-invasive tests because 64-MSCT was of insufficient
      diagnostic quality. Predictors of a poor diagnostic quality of 64-MSCT were older
      age (64+/-8 vs. 55+/-11 years, p<0.007), diabetes mellitus (42% vs. 9%, p=0.017),
      previous angiography, angioplasty or CABG surgery (83% vs. 26%, p<0.0001),
      Agatston score>400 (75% vs. 21%, p<0.002). CONCLUSION: 64-MSCT provided complete
      diagnostic coronary images sufficient for clinical decision making in the vast
      majority (78%) of a consecutive group of patients studied for suspected or proven
      CAD. Predictors of diagnostic failure were massive calcification, long-standing
      known coronary atherosclerosis or previous CABG/stent implantation, old age and
      diabetes mellitus.

PMID- 16904769
TI  - Refractory Electrical Storm suppression by bretylium.

PMID- 16904770
TI  - Metamorphosis: the natural history of coronary heart disease. Sudden death is
      common. Unexpected death is not.
AB  - It is a common practice to perform percutaneous or open coronary artery
      revascularisation in CHD to prevent sudden or unexpected death. Such a practice
      assumes that sudden and unexpected death is common in stable patients with
      uncomplicated CHD. This is a retrospective analysis of 248 patients (199, 80%
      men, 49, 20% women) who had median age 65.1 when assessed after stabilisation of
      their CHD and were followed up to 25 years until their death. Myocardial
      revascularisation was only performed after the patients had stabilised if they
      developed either progressive clinical disability or acute coronary syndromes. At
      stabilisation, 181 (73%) were uncomplicated, 59 (24%) had heart failure (HF) and
      8 (3%) had other comorbidities. At their last visit before death, 67 (27%) were
      uncomplicated, 121 (49%) had HF, 41 (17%) had cancer and 19 (8%) had other
      comorbidities. Their median age at death was 72.4 years. 77 (31%) died suddenly,
      47 (19%) of HF, 39 (16%) of cancer, 35 (14%) of acute myocardial infarction (AMI)
      and 50 (20%) had miscellaneous modes of dying. Unexpected death occurred in 26
      (10%) of cases: sudden 12, AMI 7, stroke 3, suicide 2, abdominal aneurysm 1,
      motor vehicle accident 1. We conclude that the clinical condition of most
      patients with CHD deteriorates between their initial stabilisation and their
      final visit before their death-metamorphosis. Only a small proportion of deaths
      occur in patients with stable CHD and no HF. Intervention in stable patients
      without CHF is unlikely to reduce sudden or unexpected death in patients with
      CHD.

PMID- 16904771
TI  - Severe aortic regurgitation: an exceptional cardiac manifestation of congenital
      rubella syndrome.

PMID- 16904772
TI  - An electrocardiografic mystery.

PMID- 16904773
TI  - Effect of local anesthesia and intravenous sedation on pain perception and
      vasovagal reactions during femoral arterial sheath removal after percutaneous
      coronary intervention.
AB  - BACKGROUND: There is no consensus with respect to the use of analgesia during
      femoral arterial sheath removal after percutaneous coronary intervention (PCI).
      We performed a randomized controlled trial to assess the impact of intravenous
      sedation and local anesthesia during femoral sheath removal after PCI on patient
      comfort and the incidence of vasovagal reactions. METHODS: All patients
      undergoing PCI whose femoral sheaths were to be removed with assisted manual
      compression were eligible. Patients were randomized to receive either intravenous
      sedation (Fentanyl and Midazolam) or local anesthesia (1% lignocaine) infiltrated
      around the sheath site or both or neither. The primary endpoint of the study was
      the patients reported worst pain according to a Visual Analogue scale (VAS) after
      sheath removal. The incidence and predictors of vasovagal reactions during sheath
      removal and occurrence of vascular complications was also determined. RESULTS: A
      total of 611 patients were randomized into this study. The mean pain score was
      highest in the local anesthesia only arm as compared to the sedation only arm,
      the combined local and sedation arm and the neither sedation or local arm
      (p=0.001). vasovagal reactions were experienced by 35 patients (5.1%) with the
      highest percentage in the local anesthesia only group (9.8%). Multivariate
      logistic regression analysis identified a higher pain score (OR 1.18, 95% CI 1.12
      1.24, p=0.001), use of glyceryl trinitrate during sheath removal (OR 9.05, 95% CI
      5.06-16.1, p<0.001), a lower body mass index (OR 1.12, 95% CI 1.08-1.18, p=0.009)
      and the left anterior descending artery as the treated vessel (OR 5.2, 95% CI
      3.41-7.87, p<0.001) as independent predictors of the occurrence of a vasovagal
      reaction. There was no significant difference in vascular complications between
      the 4 study groups. CONCLUSIONS: The routine use of fentanyl and midazolam prior
      to sheath removal leads to a reduction in pain perception and vasovagal
      incidence, whilst the routine use of local infiltration during sheath removal
      should be discouraged as it leads to more pain and a trend to more vasovagal
      reactions.

PMID- 16904774
TI  - Diastolic heart failure and left ventricular diastolic dysfunction: what we know,
      and what we don't know!
AB  - Diastolic heart failure is a common form of congestive heart failure that is
      responsible for significant morbidity and mortality. In contrast to heart failure
      caused by systolic left ventricular dysfunction, diastolic heart failure is
      harder to diagnose and less likely to be accepted as a diagnosis. In addition,
      treatment strategies are much less defined than those for heart failure caused by
      systolic dysfunction.

PMID- 16904775
TI  - Early diagnosis of focal myocarditis by cardiac magnetic resonance.
AB  - Early diagnosis of focal myocarditis can be difficult. We report two cases of
      myocarditis in young patients diagnosed by cardiac magnetic resonance imaging.
      The method was able to recognise the focal edema in the early phase of
      inflammation.

PMID- 16904777
TI  - Clinical and immunologic characteristics in peripartum cardiomyopathy.
AB  - Peripartum cardiomyopathy (PPCM) is a rare disorder of dilated cardiomyopathy and
      left ventricular dysfunction occurring in the last month of pregnancy or within 5
      months postpartum. Outcome of PPCM is highly variable, comprising clinical
      improvement and rapid deterioration unresponsive to medical treatment requiring
      heart transplantation or even death. In this study, we report the
      clinicopathologic findings of 10 patients with PPCM who were retrospectively
      identified in our cardiomyopathy registry. During a follow-up of 69+/-27 months,
      no patient died or required orthotopic heart transplantation. Left ventricular
      ejection fraction was 38+/-7% at the time of diagnosis and 53+/-7% during follow
      up. While all patients had sinus rhythm at the time of diagnosis, three patients
      presented with left bundle branch block. We found no evidence of viral infection
      in endomyocardial biopsy samples of seven patients by PCR. Histopathologic
      findings revealed the presence borderline myocarditis in two of seven patients
      (29%). Circulating autoantibodies to cardiac tissue of any kind were observed in
      all patients. In conclusion, in our retrospective observational study, no patient
      diagnosed with PPCM died or received orthotopic heart transplantation.
      Improvement of left ventricular ejection fraction was present in eight patients
      (80%), while LV dysfunction persisted in four patients. Our findings support the
      hypothesis of an underlying autoimmune pathomechanism in this rare disease.

PMID- 16904776
TI  - Hypertensive patients with false-positive thallium-201 scintigraphic results in
      the infero-posterior wall are in high risk for coronary artery disease
      development.
AB  - BACKGROUND: It has been previously postulated that Thallium-201 (Tl201)
      scintigraphy is characterized by relatively low specificity in hypertensive
      patients. This study was undertaken to assess any possible influence of false
      positive scintigraphic results on the prognosis of hypertensive patients.
      METHODS: The study group comprised 179 consecutive hypertensive patients (128 men
      and 51 women), aged 50+/-7 years, who underwent exercise Tl(201) scintigraphy and
      coronary angiography (patients with normal scintigraphic results underwent
      coronary angiography due to persistent angina-like symptoms). All patients with
      normal coronary arteries underwent a second Tl201 scintigraphy within 36+/-6
      months. Patients with reversible ischemia in the second scintigraphy underwent
      also a second coronary angiography. RESULTS: Coronary artery disease (CAD) was
      detected in 78 (44%) patients, while the rest 101 (56%) patients had normal
      coronary arteries. Abnormal scintigraphic results were revealed in 66 (85%)
      patients with CAD and in 38 (38%) patients without CAD. Twenty-two (58%) of the
      38 hypertensive patients with false-positive scintigraphic results presented
      reversible ischemia of the infero-posterior wall of the left ventricle. Coronary
      artery disease was detected in 7 (32%) of these patients during the follow-up
      period. CONCLUSIONS: Hypertensive patients with normal coronary arteries and
      false-positive scintigraphic results usually present with reversible ischemia of
      the infero-posterior wall of the left ventricle. This group of patients seems to
      be at increased risk of developing CAD in a long-term follow-up period.

PMID- 16904779
TI  - Molecular monitoring of the intestinal flora by denaturing high performance
      liquid chromatography.
AB  - Gut flora analysis is hampered by the complexity of the intestinal microbiota and
      by inherent limitations of culture-based approaches. Therefore, culture
      independent molecular methods based upon 16S rRNA gene analysis were applied
      successfully for the analysis of complex microbial communities. However,
      generally accepted and validated profiling methods such as denaturing and
      temperature gradient gel electrophoresis (DGGE/TGGE) are still laborious and time
      consuming. Thus, we adapted the separation of amplified bacterial 16S rRNA gene
      fragments by denaturing high performance liquid chromatography (DHPLC) using the
      WAVE Microbial Analysis System as a rapid and convenient means to display complex
      intestinal bacterial communities and to monitor changes in the gut flora. The
      separation of 16S rRNA gene fragments amplified from reference strains
      representing main gut bacterial populations and from human stool samples revealed
      that DHPLC analysis effectively detects bacterial groups predominant in the human
      gut flora. The investigation of faecal samples from hospitalized patients before,
      during and after antibiotic therapy showed that PCR-based DHPLC can be used to
      monitor gut flora changes. Results from DHPLC analysis were comparable with DGGE
      profiles generated from the same samples, demonstrating that the adapted DHPLC
      protocol is well suited for the analysis of complex microbial communities.

PMID- 16904780
TI  - Addition of glucose enables determination of luciferase activity in carbon
      starved, stationary phase Lactococcus lactis cells.
AB  - We describe a simple method for measuring luciferase activity in the stationary
      phase of Lactococcus lactis. Due to large fluctuations in the energy and redox
      pools of stationary phase bacterial cells, measurement of luciferase activities
      does not yield reliable results. Upon addition of relatively small amounts of
      glucose, the pools are restored and measurement of luciferase becomes possible.
      Since luciferase activities are easily measured, our method allows to apply this
      simple analytical tool in stationary phase cells.

PMID- 16904781
TI  - Development of a DNA microarray to identify the Streptococcus pneumoniae
      serotypes contained in the 23-valent pneumococcal polysaccharide vaccine and
      closely related serotypes.
AB  - Streptococcus pneumoniae is a major worldwide human pathogen. This investigation
      has developed a reliable and accurate DNA microarray method for inter-species
      differentiation of S. pneumoniae and intra-species differentiation of the 23
      groups of S. pneumoniae including serotypes represented in the 23-valent
      pneumococcal vaccine and the other 20 closely related serotypes. In addition to
      16S rDNA probes, serotype- or serogroup-specific probes targeting the capsular
      polysaccharide synthesis (cps) genes, wzy or capA were generated. We adopted a
      two-step multiplex PCR to improve the sensitivity of detection to a level of
      10(5) cfu/ml in pure culture or 50 ng DNA. A total of 169 isolates (from China,
      Australia, Canada and New Zealand) including 147 belonging to 23-valent vaccine
      and closely related serotypes of S. pneumoniae, 11 belonging to other serotypes
      and 11 of different species commonly isolated from respiratory tract were tested
      to verify the method. The DNA microarray method developed provides a sensitive
      means to rapidly identify the members of the most common S. pneumoniae serotypes
      in patients and to monitor their distribution in different patient groups and
      geographic locations. Such information is needed for disease surveillance and to
      monitor vaccine efficacy.

PMID- 16904782
TI  - Development of a broad-range 16S rDNA real-time PCR for the diagnosis of septic
      arthritis in children.
AB  - The broad-range PCR has been successfully developed to search for fastidious,
      slow-growing or uncultured bacteria, and is mostly used when an empirical
      antibiotic treatment has already been initiated. The technique generally involves
      standard PCR targeting the gene coding for 16S ribosomal RNA, and includes a post
      PCR visualisation step on agarose gel which is a potential source of cross-over
      contamination. In addition, interpretation of the presence of amplified products
      on gels can be difficult. We then developed a new SYBR Green-based, universal
      real-time PCR assay targeting the gene coding for 16S ribosomal RNA, coupled with
      sequencing of amplified products. The real-time PCR assay was evaluated on 94
      articular fluid samples collected from children hospitalised for suspicion of
      septic arthritis, as compared to the results obtained with bacterial cultures and
      conventional broad-range PCR. DNA extraction was performed with the automated
      MagNa Pure system. We could detect DNA from various bacterial pathogens including
      fastidious bacteria (Kingella kingae, Streptococcus pneumoniae, Streptococcus
      pyogenes, Salmonella spp, Staphylococcus aureus) from 23% of cases of septic
      arthritis giving negative culture results. The real-time technique was easier to
      interpret and allowed to detect four more cases than conventional PCR. PCR based
      molecular techniques appear to be essential to perform in case of suspicion of
      septic arthritis, provided the increase of the diagnosed bacterial etiologies.
      Real-time PCR technique is a sensitive and reliable technique, which can replace
      conventional PCR for clinical specimens with negative bacterial culture.

PMID- 16904783
TI  - A simple viability-maintaining method produces homogenic cell suspensions of
      autoaggregating wild-type Actinobacillus actinomycetemcomitans.
AB  - Tenacious adherence and autoaggregation of wild-type Actinobacillus
      actinomycetemcomitans strains jeopardize reliability of determined cell
      concentrations, e.g. for studies on bacteria-host interactions. We first compared
      the efficacy of two methods, an indirect and a direct method, for homogenizing
      cell suspensions of a wild-type, autoaggregating (SA269) strain and of a non
      autoaggregating laboratory variant (ATCC 43718) used as a reference. Since the
      direct method left visible clumps in SA269 suspension, only the indirect method
      was further tested. In serial dilutions of the homogenized cell suspensions of
      strains SA269 and ATCC 43718, the OD600 values (R2=0.99, R2=0.99, respectively)
      and protein concentrations (R2=0.93, R2=0.95, respectively) correlated
      significantly (all P<0.002) with the dilution factor. There were no differences
      (P>0.05) in the bacterial viable counts between the two strains or between
      suspending solutions, i.e., PBS and water, the cell concentrations demonstrating
      1x10(9) cells/ml at OD600=1. Repeated microscopic cell counts did not differ
      (P>0.05) from each other. Large aggregates occurred as 1% of cell units counted.
      Dispersing bacterial mass indirectly to solution leads to homogeneous cell
      suspensions with repeatable cell concentrations. Viability of A.
      actinomycetemcomitans was also maintained when cells were suspended in water.

PMID- 16904784
TI  - The forgotten variables of DNA array hybridization.
AB  - The reproducibility and reliability of DNA array measurements have been
      repeatedly questioned during the years. A reassessment of fundamental variables
      of nucleic acid hybridization might help to solve some of these problems. The
      hybridization equilibrium, t(1/2), is 41 days for a target human genome. Similar
      hybridization t(1/2) are expected for whole-transcriptome chips hybridized with
      tissue cDNA. This implies that most studies on mammalian cells have not been
      performed under equilibrium conditions. Non-equilibrium binding introduces a
      stochastic factor into hybridization dynamics; in other words, hybridization will
      prevail at different spots in different experiments, everything else being equal.
      A careful re-evaluation of results obtained under non-equilibrium conditions
      might prove fruitful and help to explain instances where findings conflict.

PMID- 16904785
TI  - Risk, society and system failure.
AB  - Modern societies are risk societies. Together with the formidable development of
      complex technologies (chemical industry, energy production, mass transportation,
      etc), new hazards have emerged. Sharing danger is the hallmark of modernity, as
      large industrial accidents can now have countrywide, or even, worldwide
      consequences. The Chernobyl explosion for example, has smeared large European
      surfaces with radioactive materials, across borders and nations, without any
      regard for who was responsible and who was the victim. Complex technologies
      should therefore be managed with great foresightness, particularly focusing on
      preventive management. A sound understanding of the (minor) role of human errors
      of operators and the (major) role of process design is a pre-requisite for
      appropriate management. This also applies to the complex business of
      radiotherapy, as the same organisational principles apply than in the heavy
      industry: restrict the role of operators, expect their mistakes, design in a
      mistake-proof way, accept the burden of preventive maintenances, supervise
      maintenance carefully and, above all, invest in safety.

PMID- 16904786
TI  - Post-movement beta synchronization after kinesthetic illusion, active and passive
      movements.
AB  - After the completion of a voluntary movement or in response to somatosensory
      stimulation, a short-lasting burst of beta oscillations (post movement beta ERS,
      beta rebound) can be observed. In the present study, we investigated if this is
      also true for the illusion of movements, induced by a vibration at 80 Hz on the
      biceps tendon. We compared the post-movement synchronization of EEG beta rhythms
      induced by active and passive movements and illusion in eight right-handed
      healthy subjects. As a result, a short-lasting post-movement beta ERS was present
      over motor areas after both active and passive and also after illusion of
      movement in all subjects. These results suggested a possible role of MI and the
      somatosensory cortex in the somatic perception of limb movement in humans.

PMID- 16904787
TI  - Layer-by-layer coating of degradable microgels for pulsed drug delivery.
AB  - Recently, we reported on "self-rupturing" microcapsules which consist of a
      biodegradable dextran-based microgel surrounded by a polyelectrolyte membrane.
      Degradation of the microgel increases the swelling pressure in the microcapsules
      which, when sufficiently high, ruptures the surrounding polyelectrolyte membrane.
      The membrane surrounding the microgels is deposited using the layer-by-layer
      (LbL) technique, which is based on the alternate adsorption of oppositely charged
      polyelectrolytes onto a charged substrate. In this paper, we characterize with
      confocal microscopy, electrophoretic mobility, scanning electron microscopy and
      atomic force microscopy in detail the deposition and the properties of the LbL
      coatings on the dextran microgels. We show that by fine-tuning the properties of
      both the microgel core and the LbL membrane the swelling pressure which is evoked
      by the degradation of the microgel is indeed able to rupture the surrounding LbL
      membrane. Further, we show that the application of an LbL coating on the surface
      of the microgels dramatically lowers the burst release from the microcapsules and
      results in massive release at the time the microcapsules rupture.

PMID- 16904789
TI  - Engineering of therapeutic antibodies to minimize immunogenicity and optimize
      function.
AB  - One of the first difficulties in developing monoclonal antibody therapeutics was
      the recognition that human anti-mouse antibody (HAMA) response limited the
      administration of murine antibodies. Creative science has lead to a number of
      ways to counter the immunogenicity of non-human antibodies, primarily through
      chimeric, humanized, de-immunized, and most recently, human-sequence therapeutic
      antibodies. Once therapeutic antibodies of low or no immunogenicity were
      available, the creativity then turned to engineering both the antigen-binding
      domains (e.g., affinity maturation, stability) and altering the effector
      functions (e.g. antibody-dependent cellular cytotoxicity, complement-dependent
      cellular cytotoxicity, and clearance rate).

PMID- 16904788
TI  - Retrospective incremental cost analysis of a hospital-based COPD Disease
      Management Programme in Sweden.
AB  - This paper reports on a retrospective analysis of hospital-based healthcare costs
      associated with the management of chronic obstructive pulmonary disease (COPD).
      During the second half of 2001, Simrishamn Hospital, Sweden, implemented a
      structured Disease Management Programme (DMP) for COPD and a total of 784
      patients with COPD, enrolled in the DMP, were included in the analysis. The goal
      was to reduce the number of clinical events, such as severe exacerbations by
      early intervention, aggressive drug treatment, specialists easy available for
      advice, improved support for smoking cessation, increased number of scheduled
      follow-ups and closer tracking of high-risk COPD patients. The hospital
      administrative system provided data on resource consumption, such as outpatient
      care, inpatient care and drugs and unit cost, used in the economic analysis. The
      total cost of COPD drugs doubled (from euro 14,133 to euro 30,855 per year) as
      did the total number of outpatient visits (from 580 to 996 visits per year). The
      number of hospitalizations for acute COPD exacerbations and COPD with acute lower
      respiratory infection decreased from 67 to 25 per year. Total COPD-related
      healthcare costs decreased. The results presented here support the hypothesis
      that a COPD DMP can offer substantial overall direct cost savings.

PMID- 16904790
TI  - Effects of initial saturation on properties modification and displacement of
      tetrachloroethene with aqueous isobutanol.
AB  - Packed column experiments were conducted to study effects of initial saturation
      of tetrachloroethene (PCE) in the range of 1.0-14% pore volume (PV) on
      mobilization and downward migration of the non-aqueous phase liquid (NAPL)
      product upon contact with aqueous isobutanol ( approximately 10 vol.%). This
      study focused on the consequences of swelling beyond residual saturation. Columns
      were packed with mixtures of neat PCE, water and glass beads and waterflooded to
      establish a desired homogeneous residual saturation, and then flooded with
      aqueous isobutanol under controlled hydraulic conditions. Results showed a
      critical saturation of approximately 8% PV for these packed column experimental
      conditions. At low initial PCE saturations (<8% PV), experimental results showed
      reduced risk of NAPL-product migration upon contact with aqueous isobutanol. At
      higher initial PCE saturations (>8% PV), results showed NAPL-product mobilization
      and downward migration which was attributed to interfacial tension (IFT)
      reduction, swelling of the NAPL-product, and reduced density modification. Packed
      column results were compared with good agreement to theoretical predictions of
      NAPL-product mobilization using the total trapping number, N(T). In addition to
      the packed column study, preliminary batch experiments were conducted to study
      the effects of PCE volumetric fraction in the range of 0.5-20% on density,
      viscosity, and IFT modification as a function of time following contact with
      aqueous isobutanol ( approximately 10 vol.%). Modified NAPL-product fluid
      properties approached equilibrium within approximately 2 h of contact for density
      and viscosity. IFT reduction occurred immediately as expected. Measured fluid
      properties were compared with good agreement to theoretical equilibrium
      predictions based on UNIQUAC. Overall, this study demonstrates the importance of
      initial DNAPL saturation, and the associated risk of downward NAPL-product
      migration, in applying alcohol flooding for remediation of DNAPL contaminated
      ground water sites.

PMID- 16904791
TI  - Probabilistic study of well capture zones distribution at the Lauswiesen field
      site.
AB  - The delineation of well capture zones is of utmost environmental and engineering
      relevance as pumping wells are commonly used both for drinking water supply
      needs, where protection zones have to be defined, and for investigation and
      remediation of contaminated aquifers. We analyze the probabilistic nature of well
      capture zones within the well field located at the "Lauswiesen" experimental
      site. The test site is part of an alluvial heterogeneous aquifer located in the
      Neckar river valley, close to the city of Tubingen in South-West Germany. We
      explore the effect of different conceptual models of the structure of aquifer
      heterogeneities on the delineation of three-dimensional probabilistic well
      catchment and time-related capture zones, in the presence of migration of
      conservative solutes. The aquifer is modeled as a three-dimensional, doubly
      stochastic composite medium, where distributions of geo-materials and hydraulic
      properties are uncertain. We study the relative importance of uncertain facies
      geometry and uncertain hydraulic conductivity and porosity on predictions of
      catchment and solute time of travel to the pumping well by focusing on cases in
      which (1) the facies distribution is random, but the hydraulic properties of each
      material are fixed, and (2) both facies geometry and material properties vary
      stochastically. The problem is tackled within a conditional numerical Monte Carlo
      framework. Results are provided in terms of probabilistic demarcations of the
      three-dimensional well catchment and time-related capture zones. Our findings
      suggest that the uncertainty associated with the prediction of the location of
      the outer boundary of well catchment at the "Lauswiesen" site is significantly
      affected by the conceptual model adopted to incorporate the heterogeneous nature
      of the aquifer domain in a predictive framework. Taking into account randomness
      of both lithofacies distribution and materials hydraulic conductivity allows
      recognizing the existence of preferential flow paths that influence the extent of
      the well catchment and the solute travel time distribution at the site.

PMID- 16904792
TI  - Morphological and physiological traits of three major Arabidopsis thaliana
      accessions.
AB  - Arabidopsis is currently the most studied organism in plant biology. Its short
      life cycle and small genome size have rendered it one of the principal model
      systems. Additionally, numerous large T-DNA insertion mutant collections are
      available. The advent of molecular biology and the completion of the Arabidopsis
      genome sequence have contributed to helping researchers discover a large variety
      of mutants identified for their phenotypes. Yet, it is important to consider that
      natural phenotypic variations exist and appear in natural ecotypes, differing
      greatly in several traits. Although there are a vast number of ecotypes
      available, only a few have been extensively studied, and some have been created
      in laboratories. In order to identify new phenotypic differences, we chose to
      study the differences observed between three ecotypes: Columbia (Col-0),
      Landsberg erecta (Laer-0) and Wassilewskija (Ws-0). Our research focuses on
      observable morphological traits throughout plant growth and development along the
      entire plant life cycle. We then attempted to shed some light on phenotypic
      discrepancies through the study of the class III peroxidase protein family, which
      is involved in many aspects of plant growth and tissue differentiation. Both
      morphological and molecular aspects reveal that there are major variations
      between ecotypes, hence indicating a possibly interesting heterotic effect in the
      F1 from crosses between different Arabidopsis ecotypes.

PMID- 16904793
TI  - A comparative study of water distribution, free radical production and activation
      of antioxidative metabolism in germinating pea seeds.
AB  - The aim of this study was to investigate whether there is a relationship between
      hydration of the embryo axes and cotyledons and the resumption of the oxidative
      metabolism in both organs of germinating seeds of pea (Pisum sativum L. cv.
      Piast). Nuclear magnetic resonance ((1)H-NMR) spectroscopy and imaging were used
      to study temporal and spatial water uptake and distribution in pea seeds. The
      observations revealed that water penetrates into the seed through the hilum,
      micropyle and embryo axes, and cotyledons hydrate to different extents. Thus,
      inhomogeneous water distribution may influence the resumption of oxidative
      metabolism. Electron paramagnetic resonance (EPR) measurements showed that seed
      germination was accompanied by the generation of free radicals with g(1) and g(2)
      values of 2.0032 and 2.0052, respectively. The values of spectroscopic splitting
      coefficients suggest that they are quinone radicals. The highest content of free
      radicals was observed in embryo axes immediately after emergence of the radicle.
      Glutathione content decreased during the entire germination period in both embryo
      axes and cotyledons. A different profile was observed for ascorbate, with
      significant increases in embryo axes, coinciding with radicle protrusion.
      Electrophoretic analysis showed that superoxide dismutase (SOD, EC 1.15.1.1),
      catalase (CAT, EC 1.11.1.6), ascorbate peroxidase (APX, EC 1.11.1.11),
      dehydroascorbate reductase (DHAR, EC 1.8.5.1) and glutathione reductase (GR, EC
      1.6.4.2) were present in dry seeds and were activated later during germination,
      especially in embryo axes. The presence of all antioxidative enzymes as well as
      low molecular antioxidants in dry seeds allowed the antioxidative machinery to be
      active as soon as the enzymes were reactivated by seed imbibition. The observed
      changes in free radical levels, antioxidant contents and enzymatic activities in
      embryo axes and cotyledons appear to be more closely related to metabolic and
      developmental processes associated with preparation for germination, and do not
      correspond directly to the hydration of the tissues.

PMID- 16904794
TI  - Neural correlates of age-related verbal episodic memory decline: a PET study with
      combined subtraction/correlation analysis.
AB  - Using PET, we have determined the neural substrates of age-related verbal
      episodic memory decline. Twelve young and twelve older healthy volunteers (mean
      age; 22 and 59 years, respectively) were scanned while performing encoding and
      retrieval tasks. Retrieval performance was lower in old than in young subjects.
      The PET data were analyzed using a combined subtraction/correlation approach.
      Classic subtraction disclosed prefrontal rCBF increases common to both groups,
      distributed bilaterally during encoding and exclusively right-sided during
      retrieval, without between-group differences. The correlation analysis between
      PET activity during encoding and subsequent retrieval performance revealed
      significant correlations for the left hippocampal region in both groups, but for
      the right inferior frontal gyrus in the older subjects only. Thus, lower
      performance in older subjects during an episodic retrieval task may reflect a
      combination of (i) subtle encoding dysfunction, evidenced by more widespread
      activity-performance correlations and (ii) less efficient retrieval, as evidenced
      by unaltered activation pattern (as revealed by the classic subtraction method)
      despite reduced performance. These exploratory findings suggest the aged brain
      may be unable to compensate for reduced efficiency of right prefrontal cortex by
      additional left frontal activation.

PMID- 16904795
TI  - In vivo antitumor, in vitro antibacterial activity and alkylating properties of
      phosphorohydrazine derivatives of coumarin and chromone.
AB  - The aim of this research was to examine chemical and biological properties of the
      products (4a-c/5a-c, 8b-c, 9a-b) of the reaction of methyl chromone-3-carboxylate
      (2), 3-formyl-4-hydroxycoumarin (3), 3-formylchromone (6) and chromone 3-carbonyl
      chloride (7) with phosphorus hydrazides (1a-c). For structure and keto-enol
      tautomerism analyses (1)H, (13)C, (31)P NMR spectroscopy was used. The ring
      transformation species (4a-c/5a-c) containing the coumarin ring (5a-c) were
      predominant in the solution. The chromone series 8b-c and 9a-b was obtained in
      reaction of phosphorus hydrazides (1a-c) with 3-formylchromone (6) and chromone-3
      carbonyl chloride (7). Alkylating activity of phosphorohydrazides of coumarin and
      chromone was determined with in vitro Preussmann test (NBP test). Some of the
      compounds were examined towards antitumor and antibacterial activity. Compounds
      4b-c/5b-c and 9a demonstrated in vitro antitumor activity against P388 leukemia.
      Antineoplastic activity of the compounds 4b/5b and 9a combined with methotrexate
      was showed using L1210 murine leukemia.

PMID- 16904796
TI  - Writing for publication: pressures, barriers and support strategies.
AB  - This paper details the increasing pressure that exists on academic and clinical
      staff to publish in the context of personal and professional development.
      Numerous barriers to writing for publication are considered along with suggested
      strategies for encouraging staff to work towards publication. Although the paper
      identifies a wealth of literature describing how to go about writing for
      publication, it is argued that this is of limited use in the support of
      individual authors, and that most authors learn academic writing skills through a
      process of trial and error. The paper is intended to encourage those wanting to
      write for publication, whilst trying to persuade those with influence on
      developing academic writing to think more broadly in regards to the support
      provided and need for research.

PMID- 16904797
TI  - Cervical cancer vaccine: the Indian sub-continental context.

PMID- 16904798
TI  - Pre-clinical evaluation of new adjuvant formulations to improve the
      immunogenicity of the malaria vaccine RTS,S/AS02A.
AB  - BACKGROUND: RTS,S/AS02A, a pre-erythrocytic Plasmodium falciparum vaccine based
      upon the circumsporozoite protein, is the only vaccine demonstrated in field
      trials to confer partial protection against a range of malaria disease
      manifestations. Pre-clinical studies are on-going to identify new RTS,S
      formulations with improved magnitude and duration of specific immunity. METHODS:
      Rhesus macaques were immunized with saline or one of four "RTS,S/adjuvant"
      formulations at 0, 4, and 12 weeks: RTS,S/AS01B, RTS,S/AS02A-standard (current
      formulation), RTS,S/AS05 or RTS,S/AS06. An RTS,S/AS02A-accelerated group was
      immunized at 0, 1, and 4 weeks. Outcomes were safety, RTS,S-specific antibody,
      and IFN-gamma and IL-5 ELISpots (weeks 14 and 34). FINDINGS: All regimens were
      safe and, except for RTS,S/AS06, generated equivalent high titer antibody levels.
      For IFN-gamma ELISpots, RTS,S/AS01B had the highest geometric mean (GM) values at
      weeks 14 and 34, and was the only group with an overall GM mean (weeks 14+34)
      higher than RTS,S/AS02A-standard (p<0.015). For IFN-gamma to IL-5 ELISpot
      response ratios, RTS,S/AS01B had the highest values at weeks 14 and 34, and was
      the only group higher than RTS,S/AS02A-standard at each individual time point and
      overall (weeks 14+34) (p<0.015). INTERPRETATION: RTS,S/AS01B is a safe and
      immunogenically superior formulation for cellular responses, in comparison with
      the RTS,S/AS02A-standard. Phase 1, 2a, and 2b clinical trials are underway to
      determine if RTS,S/AS01B demonstrates improved immunogenicity and protective
      efficacy against experimental challenge and natural mosquito-borne malaria.

PMID- 16904799
TI  - Safety evaluation of alpha-lipoic acid (ALA).
AB  - The safety of the antioxidant alpha-lipoic acid (racemic form) (ALA), also called
      thioctic acid (CAS RN 1077-28-7) was assessed in acute and subchronic toxicity
      studies as well as in in vitro and in vivo mutagenicity/genotoxicity studies. ALA
      was not acutely toxic to rats (LD(50)>2000mg/kg bw, OECD method 425).
      Administration of 31.6 or 61.9mg ALA/kg bw/day for 4 weeks to male/female Wistar
      rats did not show any adverse effects. Specifically, there was no significant
      difference between control and treated animals at 31.6 or 61.9mg ALA/kg bw with
      regard to body weight gain, feed consumption, animal behaviour, or haematological
      and clinical chemistry parameters. Only the high-dose of 121mg ALA/kg bw was
      associated with slight alterations in liver enzymes as well as histopathological
      effects on the liver and mammary gland. ALA did not possess any mutagenic
      activity in the Ames assays conducted with various bacterial strains of
      Salmonella typhimurium. Moreover, there was no evidence of genotoxic activity in
      a mouse micronucleus assay. The results of these studies support the safety of
      ALA. The no-observed-adverse-effect level (NOAEL) is considered to be 61.9mg/kg
      bw/day.

PMID- 16904800
TI  - Neighborhood disorder and smoking: findings of a European urban survey.
AB  - Using the Large Analysis and Review of European housing and health Status (LARES)
      survey, this paper investigates the influence of neighborhood physical disorder
      on smoking behaviors, and the extent to which it is mediated by perceptions of
      safety. Indicators of physical disorder: litter, graffiti, and the absence of
      vegetation on facades, balconies or windows, were directly observed by surveyors.
      The paper also considers whether the place effects on smoking are similar across
      the 7 European cities in the study. Results indicate that the odds of smoking are
      64% higher for those living in an area rated high on neighborhood disorder
      compared to low. The effect is substantially greater for men than for women with
      men in areas rated high on disorder showing odds of smoking that are twice as
      high as those living in areas rated low. The association does not vary by city of
      residence. Only a small part of the effect of neighborhood disorder is mediated
      by perceptions of safety. The finding of a substantial neighborhood physical
      disorder effect on smoking across a range of cities in Europe adds to the
      evidence suggesting that environmental interventions are worth pursuing in
      conjunction with other approaches to smoking prevention.

PMID- 16904801
TI  - Food preservatives sodium sulfite and sorbic acid suppress mitogen-stimulated
      peripheral blood mononuclear cells.
AB  - Antioxidant preservatives prolong the quality of food and ensure the nutritional
      adequacy, palatability and safety of many processed foods and beverages. Effects
      of sodium sulfite (E221) and sorbic acid (E200) were investigated in human
      peripheral blood mononuclear cells (PBMC) which were purified from blood of
      healthy donors. Cells were stimulated with the mitogen phytohaemagglutinin in
      vitro, which induces proliferation of T-cells and the production of Th1-type
      cytokines like interferon-gamma. The latter triggers enzyme indoleamine (2,3)
      dioxygenase, which degrades tryptophan, and GTP cyclohydrolase I, which leads to
      increased neopterin production, in monocyte-derived macrophages. Sodium sulfite
      and sorbic acid suppressed both these biochemical changes in a dose-dependent way
      (P<0.01 at 1 mM sodium sulfite and 50 mM sorbic acid). Data demonstrate a
      suppressive influence of sodium sulfite and sorbic acid on the activated Th1-type
      immune response.

PMID- 16904802
TI  - Cephalopod tropomyosins: identification as major allergens and molecular cloning.
AB  - Heated extracts prepared from the mantle muscles (for decapods) or leg muscles
      (for octapods) of nine species of cephalopods were shown to be all reactive with
      serum IgE in crustacean-allergic patients. No marked difference in the reactivity
      with IgE was recognized among the cephalopods, suggesting that they are almost
      equally allergenic. Immunoblotting and inhibition immunoblotting data revealed
      that the major allergen is tropomyosin in common with the nine species of
      cephalopods and that the cephalopod tropomyosins are cross-reactive with one
      another and also with crustacean tropomyosins. Molecular cloning experiments
      first elucidated the primary structures of tropomyosins from five species of
      cephalopods. The cephalopod tropomyosins show high sequence identity (more than
      92% identity) with one another, being the molecular basis for their cross
      reactivity. Although the sequence identity between cephalopod and crustacean
      topomyosins is only about 63-64%, some of the IgE-binding epitopes proposed for
      brown shrimp Penaeus aztecus tropomyosin (Pen a 1) are well conserved in the
      cephalopod tropomyosins, supporting the cross-reactivity between cephalopod and
      crustacean tropomyosins.

PMID- 16904803
TI  - Inhibition of P-glycoprotein-mediated transport by terpenoids contained in herbal
      medicines and natural products.
AB  - Terpenoids form a large and structurally diverse family of natural products and
      are ingredients of various herbal medicines. We have investigated possible
      interactions between herbal medicines and conventional medicines, and recently
      reported that monoterpenoids contained in Zanthoxyli Fructus can be potent
      inhibitors of P-glycoprotein (P-gp). In the present study, the influence of 70
      kinds of terpenoids present in natural products on P-gp-mediated efflux transport
      was investigated. LLC-GA5-COL150 cells transfected with human MDR1 cDNA encoding
      P-gp were used to screen the terpenoids. Large increases in the intracellular
      accumulation of [(3)H]digoxin were observed in the presence of (R)-(+)
      citronellal, (S)-(-)-beta-citronellol, alpha-terpinene, terpinolene, (-)-beta
      pinene, abietic acid, ophiobolin A, cucurbitacin I, and glycyrrhetic acid. A
      study of the concentration-dependency revealed that the IC(50) of ophiobolin A,
      glycyrrhetic acid, (R)-(+)-citronellal, abietic acid, and cucurbitacin I was
      smaller than that of verapamil. The transcellular transport of [(3)H]digoxin
      across Caco-2 cell monolayers was then examined in the presence of (R)-(+)
      citronellal, abietic acid, and glycyrrhetic acid. Significant increases in the
      apical-to-basolateral transport and decreases in the basolateral-to-apical
      transport and efflux ratio were demonstrated. These findings suggest that some
      natural products containing these terpenoids may inhibit P-gp-mediated transport
      and interact with P-gp substrates in the intestinal absorption process.

PMID- 16904804
TI  - Sugars as tobacco ingredient: Effects on mainstream smoke composition.
AB  - Sugars are natural tobacco components, and are also frequently added to tobacco
      during the manufacturing process. This review describes the fate of sugars during
      tobacco smoking, in particular the effect of tobacco sugars on mainstream smoke
      composition. In natural tobacco, sugars can be present in levels up to 20 wt%. In
      addition, various sugars are added in tobacco manufacturing in amounts up to 4
      wt% per sugar. The added sugars are usually reported to serve as flavour/casing
      and humectant. However, sugars also promote tobacco smoking, because they
      generate acids that neutralize the harsh taste and throat impact of tobacco
      smoke. Moreover, the sweet taste and the agreeable smell of caramelized sugar
      flavors are appreciated in particular by starting adolescent smokers. Finally,
      sugars generate acetaldehyde, which has addictive properties and acts
      synergistically with nicotine in rodents. Apart from these consumption-enhancing
      pyrolysis products, many toxic (including carcinogenic) smoke compounds are
      generated from sugars. In particular, sugars increase the level of formaldehyde,
      acetaldehyde, acetone, acrolein, and 2-furfural in tobacco smoke. It is concluded
      that sugars in tobacco significantly contribute to the adverse health effects of
      tobacco smoking.

PMID- 16904805
TI  - Mutagenicity of arbutin in mammalian cells after activation by human intestinal
      bacteria.
AB  - Arbutin (hydroquinone-beta-D-glucopyranoside) is present in various food plants.
      Its aglycone, hydroquinone, is mutagenic and carcinogenic. We investigated
      whether hydroquinone may be released under conditions encountered in the human
      gastrointestinal tract. Arbutin was stable in artificial gastric juice. Fecal
      slurries from nine human subjects completely converted arbutin (2 mM) into
      hydroquinone. Four of nine representative human intestinal species investigated,
      namely Eubacterium ramulus, Enterococcus casseliflavus, Bacteroides distasonis,
      and Bifidobacterium adolescentis, deglycosylated arbutin at rates of 21.08,
      16.62, 8.43 and 3.59 nmol x min(-1) x (mg protein)(-1), respectively. In
      contrast, homogenates from small intestinal mucosa and cytosolic fractions from
      colon mucosa deglycosylated arbutin at substantially lower rates: 0.50 and 0.09
      nmol x min(-1) x (mg protein)(-1), respectively. Arbutin, unlike hydroquinone,
      did not induce gene mutations in Chinese hamster V79 cells in the absence of an
      activating system. However, in the presence of cytosolic fractions from E.
      ramulus or B. distasonis, arbutin was strongly mutagenic. Cytosolic fraction from
      Escherichia coli, showing no arbutin glycosidase activity, was not able to
      activate arbutin in this model system. The release of the proximate mutagen
      hydroquinone from arbutin by intestinal bacteria in the immediate vicinity of the
      colon mucosa may pose a potential risk.

PMID- 16904806
TI  - Supplementation of whole persimmon leaf improves lipid profiles and suppresses
      body weight gain in rats fed high-fat diet.
AB  - The objective of this study was to investigate the hypolipidemic effects of
      powdered whole persimmon leaf supplement in rats fed high-fat diet. Three groups
      of male Sprague-Dawley rats during 6 weeks were fed different diet: normal
      control (NC), high-fat (HF), and high-fat supplemented with powdered whole
      persimmon leaf (PL; 5%, wt/wt) groups. Body weight and relative weight of
      interscapular brown adipose tissue were significantly lower in the PL group than
      in the HF group, while plasma leptin concentration was higher. The
      supplementation of persimmon leaf significantly lowered the plasma total
      cholesterol and triglyceride concentrations, whereas elevated the ratio of HDL
      C/total-C and improved the atherogenic index. Persimmon leaf supplementation led
      the hepatic cholesterol and triglyceride values to similar levels to the NC
      group. Accumulation of hepatic lipid droplets and the epididymal white adipocyte
      size of PL group were diminished comparing to the HF group. Hepatic HMG-CoA and
      ACAT activities were significantly higher in the PL group than in other groups.
      Contents of fecal triglyceride, cholesterol and acidic sterol were significantly
      higher in the PL group than in the HF group. Accordingly, we suggest that
      supplementation of the powdered whole persimmon leaf improves plasma and hepatic
      lipid levels profile partly via the increased fecal lipids in high-fat fed rats.
      These beneficial effects may be due to the properties of its phenolic compounds
      (1.15 g/100g) and high fiber (63.48 g/100g) content in the powdered persimmon
      leaf.

PMID- 16904807
TI  - Simulation of cholinesterase status at different scenarios of nerve agent
      exposure.
AB  - The ongoing threat of homicidal use of organophosphorus-type chemical warfare
      agents ("nerve agents") during military conflicts and by terrorists underlines
      the necessity for effective medical countermeasures. Standard treatment with
      atropine and the established acetylcholinesterase (AChE) reactivators, obidoxime
      and pralidoxime, is considered to be ineffective with certain nerve agents due to
      low oxime effectiveness. From obvious ethical reasons only animal experiments can
      be used to evaluate new oximes as nerve agent antidotes. However, the
      extrapolation of data from animal to humans is hampered by marked species
      differences. Since reactivation of OP-inhibited AChE is considered to be the main
      mechanism of action of oximes, human erythrocyte AChE can be exploited to test
      the efficacy of new oximes. Recently, a dynamic computer model was developed
      which allows the calculation of AChE activities at different scenarios by
      combining enzyme kinetics (inhibition, reactivation, aging) with OP
      toxicokinetics and oxime pharmacokinetics. Now, this computer model was further
      extended by including the pharmaco- and enzyme kinetics of carbamate
      pretreatment. Simulations were performed for intravenous and percutaneous nerve
      agent exposure and intramuscular oxime treatment in the presence and absence of
      pyridostigmine pretreatment using published data. The model presented may serve
      as a tool for evaluating the impact of carbamate pretreatment on oxime-induced
      reactivation of inhibited AChE, for defining effective oxime concentrations and
      for optimizing oxime treatment. In addition, this model may be useful for the
      development of meaningful therapeutic strategies in animal experiments.

PMID- 16904808
TI  - Evaluation of HI 6 treatment after percutaneous VR exposure by use of a kinetic
      based dynamic computer model.
AB  - The availability of highly toxic OP-type chemical warfare agents (nerve agents)
      and the exertion of organophosphorus compounds during military conflicts and
      terrorist attacks against civilians in the past underlines the necessity of an
      effective treatment regimen of OP-poisoning. Presently, standard treatment
      includes administration of an antimuscarinic agent (e.g. atropine) and a
      reactivator of inhibited AChE (oxime), but is considered to be rather ineffective
      with certain nerve agents due to low oxime effectiveness of the currently
      available oximes, obidoxime and pralidoxime. The evaluation of new oximes as
      antidotes relies on the implementation of animal experiments for ethical reasons
      and is complicated by a limited extrapolation of animal data to humans. The
      development of a reliable animal model might accelerate the evaluation of new
      substances and their approval as antidotes, whereas, the pig as higher mammalian
      species seems to be promising as model animal. A dynamic in vitro model, which
      allows the calculation of AChE activities at different scenarios was developed to
      facilitate the definition of effective oxime concentrations and the optimization
      of oxime treatment of OP poisoning of humans and may furthermore be helpful by
      designing animal experiments. The model is based on a combination of enzyme
      kinetics (inhibition, reactivation, aging) of AChE with OP, toxicokinetics and
      oxime pharmacokinetics. By considering species-specific kinetic data this dynamic
      model was used for the calculation of AChE activities in humans and pigs after
      percutaneous exposure with 5x LD(50) VR (Russian VX) and treatment with HI 6, a
      promising new reactivator of OP-inhibited AChE. Due to a low affinity of HI 6
      with VR-inhibited pig AChE the oxime dose that causes maximal reactivation of VR
      inhibited pig AChE is conspicuously higher compared to humans. Therefore, the
      design of animal experiments in consideration of calculated data based on species
      specific kinetic values may lead to a more reliable extrapolation of animal data
      to humans and may reduce the number of necessary animal experiments.

PMID- 16904809
TI  - Enzyme-kinetic investigation of different sarin analogues reacting with human
      acetylcholinesterase and butyrylcholinesterase.
AB  - The pertinent threat of using organophosphorus compound (OP)-type chemical
      warfare agents (nerve agents) during military conflicts and by non-state actors
      requires the continuous search for more effective medical countermeasures. OP
      inhibit acetylcholinesterase (AChE) and therefore standard treatment of
      respective poisoning includes AChE reactivators (oximes) in combination with
      antimuscarinic agents. Hereby, standard oximes, 2-PAM and obidoxime, are
      considered to be rather insufficient against various nerve agents. Numerous
      experimental oximes have been investigated in the last decades by in vitro and in
      vivo models. Recently, we studied the reactivating potency of several oximes with
      human AChE inhibited by structurally different OP and observed remarkable
      differences depending on the OP and oxime. In order to investigate structure
      activity relationships we determined the various kinetic constants (inhibition,
      reactivation, aging) for a series of sarin analogues bearing a methyl, ethyl, n
      propyl, n-butyl, i-propyl, i-butyl, cyclohexyl or pinacolyl group with human AChE
      and BChE. The rate constants for the inhibition of human erythrocyte AChE and
      plasma BChE by these OP (k(i)), for the spontaneous dealkylation (k(a)) and
      reactivation (k(s)) of OP-inhibited AChE and BChE as well as for the oxime
      induced reactivation of OP-inhibited AChE and BChE by the oximes obidoxime, 2
      PAM, HI 6, HLo 7 and MMB-4 were determined. With compounds bearing a n-alkyl
      group the inhibition rate constant increased with chain length. A relation
      between chain length and spontaneous reactivation velocity was also observed. In
      contrast, no structure-activity dependence could be observed for the oxime
      induced reactivation of AChE and BChE inhibited by the compounds tested. In
      general, OP-inhibited AChE and BChE were susceptible towards reactivation by
      oximes. HLo 7 was the most potent reactivator followed by HI 6 and obidoxime
      while 2-PAM and MMB-4 were rather weak reactivators. These data indicate a
      potential structure-activity relationship concerning inhibition and spontaneous
      reactivation but not for oxime-induced reactivation.

PMID- 16904810
TI  - Transcriptional and translational regulation of BACE1 expression--implications
      for Alzheimer's disease.
AB  - The proteolytical processing of the amyloid precursor protein (APP) gives rise to
      beta-amyloid peptides, which accumulate in brains of Alzheimer's disease (AD)
      patients. Different soluble or insoluble higher molecular weight forms of beta
      amyloid peptides have been postulated to trigger a complex pathological cascade
      that may cause synaptic dysfunction, inflammatory processes, neuronal loss,
      cognitive impairment, and finally the onset of the disease. The generation of
      beta-amyloid peptides requires the proteolytical cleavage of APP by an aspartyl
      protease named beta-site APP-cleaving enzyme 1 (BACE1). The expression and
      enzymatic activity of BACE1 are increased in brains of AD patients. Here we
      discuss the importance of a number of recently identified transcription factors
      as well as post-transcriptional modifications and activation of intracellular
      signaling molecules for the regulation of BACE1 expression in brain. Importantly,
      some of these factors are known to be involved in the inflammatory and chronic
      stress responses of the brain, which are compromised during aging. Moreover,
      recent evidence indicates that beneficial effects of non-steriodal anti
      inflammatory drugs on the progression of AD are mediated--at least in part--by
      effects on the peroxisome proliferator-activated receptor-gamma response element
      present in the BACE1 promoter. The identification of the cell type-specific
      expression and activation of NF-kappaB, Sp1 and YY1 transcription factors may
      provide a basis to specifically interfere with BACE1 expression and, thereby, to
      lower the concentrations of beta-amyloid peptides, which may prevent neuronal
      cell loss and cognitive decline in AD patients.

PMID- 16904811
TI  - Relationship between salivary cortisol and progesterone levels in humans.
AB  - In four studies, each with multiple hormone assessments before and after positive
      emotion-arousing laboratory manipulations, salivary progesterone positively
      correlated with salivary cortisol in men and women taking hormonal contraceptives
      but not in freely cycling women. This is consistent with the idea that
      progesterone in men is largely adrenal in origin, whereas in women its sources
      are both ovarian and adrenal. In addition, bi-partial correlations revealed that
      change in cortisol was positively related to change in progesterone levels; this
      effect was stronger in men than in women. These findings suggest that
      progesterone is released from the adrenal along with cortisol in humans, due to
      general adrenal activation and/or possibly as an additional negative feedback
      mechanism to down-regulate the stress response.

PMID- 16904812
TI  - Evidence for a dopaminergic link between working memory and agentic extraversion:
      an analysis of load-related changes in EEG alpha 1 activity.
AB  - Several lines of research point to the possibility of a partially overlapping
      dopaminergic foundation of the trait of agentic extraversion and individual
      differences in working memory functioning. This study investigates interactive
      effects of agentic extraversion and dopamine on spectral EEG measures of working
      memory. Using EEG activity in the alpha 1 band (8-10.25 Hz) as a dependent
      variable, we tested in a randomized double-blind design the effects of the D2
      dopamine antagonist sulpiride during the performance of four load-graded n-back
      working memory tasks in participants high versus low in agentic extraversion. We
      expected extraversion-related differences in the load-responsivity pattern to be
      reversed by sulpiride, and the alpha 1 anterior-posterior difference actually
      depicted this reversal effect. However, in contrast to our expectations this
      effect was largely due to parietal instead of frontal sites.

PMID- 16904813
TI  - Obstetric management and outcome of pregnancy in women with a history of
      caesarean section in the Netherlands.
AB  - OBJECTIVE: To determine mode of delivery and occurrence of uterine rupture in
      women with a previous caesarean section (CS) in the Netherlands. MATERIALS AND
      METHODS: During a 1-year period 38 hospitals in the Netherlands registered
      prospectively mode of delivery, use of prostaglandins or oxytocin and occurrence
      of uterine rupture in all women with a previous CS. RESULTS: There were 4569
      women with a previous CS. Trial of labour (TOL) was attempted in 71.7%, of whom
      76.0% delivered vaginally. The vaginal birth after caesarean (VBAC)-rate was
      54.4%. Forty-nine uterine ruptures occurred (1.1%), of which 48 occurred during a
      TOL (1.5%). There were four perinatal deaths (1.2/1000 TOL) and 3 hysterectomies
      (0.9/1000 TOL) related to the rupture. Use of prostaglandin E2 alone or combined
      with oxytocin was significantly associated with an increased risk of uterine
      rupture (OR 6.8, 95% CI 3.2-14.3, OR 4.8, 95% CI 1.6-14.6, respectively). The
      same held for augmentation with oxytocin (OR 2.2, 95% CI 1.04-5.0). CONCLUSION:
      The success rate of TOL was 76%, resulting in a VBAC rate of 54%. Uterine rupture
      occurred in 1.5% during a TOL, with a risk of perinatal death of 1.2 per 1000.
      The risk of uterine rupture increased significantly when labour was induced with
      prostaglandins alone or combined with oxytocin or when labour was augmented with
      oxytocin.

PMID- 16904814
TI  - Perceptions and attitudes of land managers in multi-tenure reserve networks and
      the implications for conservation.
AB  - Multi-tenure reserve networks aim to connect areas managed for biodiversity
      conservation across public and private land and address the impacts of
      fragmentation on both biotic and social systems. The operation and function of
      Australian multi-tenure reserve networks as perceived by their land managers was
      investigated. Overall, the conservation of natural assets was the most frequently
      reported primary reason for involvement in a network. The perceived aims of the
      respective networks largely reflected the response identified for involvement and
      management. Over 88% of managers considered their involvement in multi-tenure
      reserve networks to be a positive or very positive experience. A lack of
      resources and time for management were considered major limitations of these
      networks. The majority (80%) of private land managers within networks were
      willing to be included in a national reserve system of conservation lands. As the
      Australian National Reserve System currently incorporates mostly public land,
      these findings have important and potentially positive implications for a greater
      role for protected private land.

PMID- 16904815
TI  - Hydronephrosis as a prognostic marker in bladder cancer in a cystectomy-only
      series.
AB  - OBJECTIVES: Hydronephrosis in patients with bladder cancer is caused by tumour at
      the ureteral orifice, secondary ureteral tumours, intramural or extravesical
      tumour infiltration, or compression of the ureter. This study investigated the
      prognostic impact of hydronephrosis in bladder cancer. METHODS: A series of 788
      patients were treated with radical cystectomy with curative intent for
      transitional cell carcinoma of the bladder without neoadjuvant/adjuvant
      radiotherapy/chemotherapy between January 1986 and September 2003. All patients
      had a complete follow-up until death or until the study's end date. Survival
      rates were calculated using the Kaplan-Meier method. A multivariate analysis with
      a Cox regression model was performed with respect to potential influencing
      factors. RESULTS: A total of 108 patients (13.7%) had unilateral and 25 patients
      (3.2%) had bilateral hydronephrosis. The rate of organ-confined tumours was
      significantly higher in patients without hydronephrosis (67.9% vs. 37.6%;
      p<0.001). Forty-three (32.3%) of the 133 hydronephrotic patients had a tumour
      involving the ureteral orifice. In this group the rate of organ-confined tumours
      was significantly higher than in the other patients with hydronephrosis (53.5%
      vs. 30.0%; p=0.009). In the multivariate analysis, preoperative hydronephrosis
      was determined as an independent prognostic marker for recurrence-free survival
      besides the pT classification and lymph node status (p=0.0015). The etiology of
      hydronephrosis did not affect the tumour-specific survival. CONCLUSIONS:
      Hydronephrosis at the time of diagnosis of bladder cancer is associated with a
      high probability of advanced tumours. It is an independent prognostic factor for
      recurrence-free survival.

PMID- 16904816
TI  - Staged pendulous-prostatic anastomotic urethroplasty followed by reconstruction
      of the anterior urethra: an effective treatment for long-segment bulbar and
      membranous urethral stricture.
AB  - OBJECTIVES: To describe a novel surgical technique for male long-segment urethral
      stricture after pelvic trauma using the intact and pedicled pendulous urethra to
      replace the bulbar and membranous urethra, followed by reconstruction of the
      anterior urethra. METHODS: Two patients with long-segment post-traumatic bulbar
      and membranous urethral strictures with short left pendulous urethras who had
      undergone several failed previous surgeries were treated with staged pendulous
      prostatic anastomotic urethroplasty followed by reconstruction of the anterior
      urethra. This procedure was divided into three stages. First-stage surgery was
      mobilization of the anterior urethra down to the coronary sulcus and then
      rerouted to the prostatic urethra followed by pendulous-prostatic anastomotic
      urethroplasty with transposition of the penis to the perineum. Second-stage
      surgery was transecting the anterior urethra at the revascularised coronary
      sulcus 6 mo later, followed by straightening of the penis and
      urethroperineostomy. Third-stage surgery was reconstruction of the anterior
      urethra 6 mo later. RESULTS: Postoperatively, the two patients reported
      satisfactory voiding. For patient 1, retrograde urethrography showed that the
      urethra was patent, and that the mean maximal flow rate (MFR) was 18.4 ml/s with
      no postvoiding residual urine after the third-stage surgery and at 3-yr follow
      up. For patient 2, a 22F urethral catheter could pass smoothly through the
      urethra, and the MFR was 19.5 ml/s with no postvoiding residual urine at 2-yr
      follow-up. CONCLUSIONS: This procedure was an effective surgical option for men
      with complex long-segment post-traumatic bulbar and membranous urethral
      strictures, especially for those who had undergone failed previous surgical
      treatments.

PMID- 16904817
TI  - Preservation of the puboprostatic collar and puboperineoplasty for early recovery
      of urinary continence after robotic prostatectomy: anatomic basis and preliminary
      outcomes.
AB  - OBJECTIVES: The aims of the present study are to prove the hypothesis that the
      preservation of the puboprostatic collar and puboperineoplasty contribute to the
      early recovery of urinary continence after robotic radical prostatectomy. We
      reconfirm the anatomy of the periurethral supporting tissue and show the
      preliminary result on the early continence of patients undergoing this
      modification. METHODS: Using 10, male, fresh cadavers, we traced the endopelvic
      fascia, the fascia of levator ani, puboprostatic ligaments, rhabdosphincter, and
      puboperinealis muscle to devise strategies in preserving this complex. The
      modifications were then attempted by a single surgeon (A.K.T.) in 19 patients
      undergoing robotic prostatectomy during September 2005. RESULTS: After incision
      of the endopelvic fascia within the fascial tendinous arch of the pelvis, the
      puboprostatic collar and the levator ani could be separated laterally. The
      puboperinealis muscle attached to part of the pubic symphysis behind the
      puboprostatic ligament and terminated at the perineal body. We were able to
      preserve the puboprostatic collar in all attempted cases. Furthermore,
      puboperineoplasty took 5min to complete. The total continence rate was 63.2% at
      median follow-up of 38.1 d. Immediate continence rate just after catheter removal
      was 42.1%. The rate at 1 and 4 wk was 52.6% and 71.4%, respectively. The margins
      of the examined specimens were all negative for malignancy. CONCLUSIONS: This
      modification should preserve or allow for early recovery of urinary continence
      from an anatomic perspective. Further studies are necessary to elucidate the
      clinical impact on a patient's early continence.

PMID- 16904818
TI  - Zonal origin of localized prostate cancer does not affect the rate of biochemical
      recurrence after radical prostatectomy.
AB  - OBJECTIVE: To investigate whether transition zone (TZ) prostate cancers
      demonstrate different rates of biochemical recurrence after radical prostatectomy
      compared to peripheral zone (PZ) cancers. METHODS: In 1262 consecutive patients
      treated with radical prostatectomy, computerized planimetry defined tumour origin
      as either TZ tumours (>70% TZ location) or PZ. Kaplan-Meier and multivariate Cox
      regression models tested the association between zonal origin and the rate of
      biochemical recurrence (prostate-specific antigen >0.1ng/ml and rising). We used
      the Harrell's concordance index to quantify the accuracy of various Cox
      regression models. RESULTS: TZ prostate cancers were diagnosed in 115 patients
      (9.1%). Biochemical recurrence was recorded in 16 TZ and in 201 PZ prostate
      cancers patients. In multivariate Cox models, the rate of biochemical recurrence
      was not significantly different between TZ and PZ prostate cancers (p=0.4).
      Combined multivariate predictive accuracy of biochemical recurrence predictions
      was 81.2% accurate when zonal origin was included versus 81.0% when zonal origin
      was omitted. CONCLUSIONS: The zonal origin of prostate cancers does not affect
      the rate of biochemical recurrence after radical prostatectomy.

PMID- 16904819
TI  - Proposal for reclassification of the TNM staging system in patients with locally
      advanced (pT3-4) renal cell carcinoma according to the cancer-related outcome.
AB  - OBJECTIVES: The optimal stratification of locally advanced renal cell carcinoma
      (RCC) is controversial, with the prognostic relevance of ipsilateral adrenal
      gland invasion and cranial extension of vena cava thrombosis being the most
      debatable issues. We evaluated the prognosis of patients with locally advanced
      RCC and identified a new model to stratify their outcome. MATERIALS AND METHODS:
      We analyzed the data of 227 patients who had undergone partial or radical
      nephrectomy for pT3-4 RCC at two academic centers between 1986 and 2002. The log
      rank test and Cox proportional hazards model were used for univariate and
      multivariate analysis, respectively. RESULTS: At a median follow-up of 29 mo, we
      censored 108 (47.6%) cancer-related deaths. On univariate analysis, the 2002 T
      stage was not statistically significant. According to cancer-related outcome, we
      identified three subgroups of patients with different prognoses: pT3a(n): tumors
      with perirenal fat invasion or renal vein thrombosis or thrombosis within the
      vena cava below the diaphragm; pT3b(n): tumors with renal vein thrombosis or
      thrombosis within the vena cava below the diaphragm and concomitant perirenal fat
      invasion; pT4(n): adrenal gland or Gerota fascia invasion or thrombosis within
      the vena cava above the diaphragm. The three subgroups had significantly
      different prognoses. The new reclassification was an independent predictive
      variable on multivariate analysis, as well as the pathologic lymph node stage.
      CONCLUSIONS: The 2002 version of TNM of locally advanced RCC did not stratify
      patient outcome. The present study suggests the possibility of reclassifying pT3
      4 RCC into three categories capable of predicting cancer-specific survival,
      regardless of all other prognostic factors.

PMID- 16904820
TI  - Binary mixtures exhibiting maximum flash-point behavior.
AB  - This study has demonstrated the existence of maximum flash-point solutions, where
      the maximum flash-point value is larger than those of the individual components.
      The behavior of such a solution has potential application in hazard reduction.
      The sufficient condition for a binary mixture to form such a maximum flash-point
      solution, and the equations to determine its composition and maximum flash point
      are proposed here, as these may be important in terms of hazard reduction. The
      sufficient condition and associated equations were verified by comparison with
      the experimental data. Our results reveal that this derived condition is
      satisfactory to establish that a liquid mixture is a maximum flash-point
      solution. The proposed equations may be successfully applied to estimate the
      composition and maximum flash-point value of such a mixture.

PMID- 16904821
TI  - A novel acid-sensitive K+ channel in rat dorsal root ganglia neurons.
AB  - Recent studies have suggested that acid-sensitive background K+ channels such as
      TASK-1 and TASK-3, members of two-pore domain K+ (K2P) channel family, express
      and contribute to extracellular acidification-induced responses in dorsal root
      ganglia (DRG) neurons. However, it has remained to address whether other acid
      sensitive background K+ channels are functionally expressed in DRG neurons. Here
      we characterized biophysical and pharmacological properties of a novel acid
      sensitive background K+ channel in DRG neurons isolated from neonatal rats. We
      recorded an 80-pS K+ channel with a weak inward rectification current-voltage
      relationship in cell-attached patches in 150mM KCl bath solution. The 80-pS K+
      channel was inhibited by extracellular low pH (pHo 6.3). Interestingly, the
      channel was similar to TASK-2 cloned from mouse and rat in biophysical and
      pharmacological properties. However, extracellular alkaline condition which
      activates TASK-2 channel, failed to activate the 80-pS K+ channel. Lidocaine and
      quinine more inhibited the channel activity of 80-pS K+ channel than that of TASK
      2 channel. Our results suggest that the acid-sensitive 80-pS K+ channels may
      regulate resting membrane potential and may play a critical role in various
      processes such as cell metabolism, pH, and pain sensation in DRG neurons.

PMID- 16904822
TI  - RGS4 polymorphisms and risk of schizophrenia: an association study in Han Chinese
      plus meta-analysis.
AB  - Recently, several researches based on expression analysis, genetic linkage and
      association studies have suggested that the regulator of G-protein signaling 4
      (RGS4) might be a schizophrenia susceptibility gene. However, these linkage and
      association studies have been conducted using different ethnic samples, and have
      therefore tended to produce inconsistent results. To help to clarify this
      inconsistency, we used non-family based samples to carry out a case-control
      analysis on six single nucleotide polymorphisms (SNPs) (including four widely
      investigated SNPs, SNP1, 4, 7, 18 and another two SNPs, rs2842030 and rs2344671)
      in a Chinese Han sample set comprising 288 schizophrenia patients and 288 normal
      controls. All genotypings were conducted by direct sequencing and all SNPs were
      in Hardy-Weinberg equilibrium. We found no individual SNPs or haplotypes to be
      associated with schizophrenia. We also performed a meta-analysis based on all
      published population-based association studies on the topic including our own.
      The results of both our case-control study in the Chinese Han population and the
      meta-analysis yield no significant evidence for association, which suggests that
      the genetic polymorphisms within RGS4 are unlikely to confer an increased
      susceptibility to the etiology of schizophrenia.

PMID- 16904823
TI  - Volumetric correlates of memory and executive function in normal elderly, mild
      cognitive impairment and Alzheimer's disease.
AB  - In Alzheimer's disease (AD), atrophy negatively impacts cognition while in
      healthy adults, inverse relationships between brain volume and cognition may
      occur. We investigated correlations between gray matter volume and cognition in
      elderly controls, AD and mild cognitive impairment (MCI) patients with memory and
      executive deficits. AD demonstrated substantial loss in temporal, parietal and
      frontal regions while MCI exhibited moderate volume loss in temporal and frontal
      regions. In controls, memory and executive function were negatively correlated
      with frontal regions, while in AD, memory was positively correlated with temporal
      and frontal gyri, and executive function with frontal regions. The combination of
      the two patterns may explain the lack of correlations in MCI. Developmental
      versus pathological contributions to these relationships are discussed.

PMID- 16904824
TI  - Spikelet currents in frog tectal neurons with different firing patterns in vitro.
AB  - Neuronal potential-dependent membrane currents are important in shaping the
      integration of synaptic inputs. Our recordings in voltage-clamp mode indicate
      that the small fast inward currents (spikelet currents), which were several times
      smaller than action potential (AP) currents, are a distinguished feature of 33%
      of neurons from 8 to 6 layers of the frog tectum. Out of all neuronal types
      described previously, only phasic cells and neurons with 'sag' in response to
      hyperpolarizing step current injection did not show spikelet currents. These
      small fast inward currents were sensitive to the intracellular administration of
      the sodium channel blocker QX-314, but not to the extracellular application of a
      glutamate receptor antagonist kynurenic acid. This suggests that spikelet
      currents are mediated by fast voltage-dependent Na(+) channels. Since spikelet
      currents could also be elicited with synaptic stimulation it is possible that
      spikelets are generated in dendrites and, thus, are important for fast
      integration of visual signals in tectal neurons.

PMID- 16904825
TI  - Excitability of subcortical motor circuits in Go/noGo and forced choice reaction
      time tasks.
AB  - The size of the response to a startling auditory stimulus (SAS) may reflect the
      excitability of the reticulospinal tract. In this study, we examined whether
      there was any excitability change in the reticulospinal tract during preparation
      for execution of two types of choice reaction time task: a forced choice reaction
      time task (fCRT) and a Go/no-Go task (GnG). In 13 healthy volunteers we used
      three types of trials: control trials in which subjects were requested to perform
      ballistic wrist movements during fCRT or GnG tasks; test trials in which a SAS
      was presented with the visual cue, and baseline trials in which SAS was presented
      alone. Latency and area of the responses to SAS were measured in the orbicularis
      oculi and in the sternocleidomastoid (SCM) muscles. The results obtained in
      baseline trials were used to calculate the mean resting baseline excitability
      level of the reticulospinal tract for each individual, and the values obtained in
      test trials were expressed as percentages of mean baseline for normalization of
      data from all individuals. The area of the responses to SAS in SCM was
      significantly larger in fCRT than in GnG (p=0.002). There was a significant
      shortening of reaction time in test trials that was inversely correlated with
      area of SCM (p<0.05). We conclude that the subcortical motor tracts activated by
      SAS are more excitable during fCRT tasks than GnG tasks. Changing the
      excitability of subcortical motor structures may be a strategy used by the
      central nervous system in motor control that is selected according to the motor
      program.

PMID- 16904826
TI  - Testing the role of calmodulin in the excitation of Limulus photoreceptors.
AB  - The phototransduction cascade in Limulus ventral photoreceptors involves multiple
      second messengers, including Ca(2+) and cGMP. Light-induced Ca(2+) release from
      intracellular stores is an intermediate step, but the subsequent Ca(2+)-activated
      reaction remains to be determined. The possibility that Ca(2+)/calmodulin
      (Ca(2+)/CaM) might be involved is suggested by the high calmodulin content of the
      transducing lobe. To test whether CaM can excite the transduction cascade we
      injected a 25 microM Ca(2+)/CaM solution. This produced a rapid, brief
      depolarization similar to that produced by light, suggesting a role for CaM in
      the cascade. However, an important caveat is that Ca(2+) dissociating from the
      Ca(2+)/CaM complex might excite this process. Several control experiments argue
      against, but do not entirely eliminate this possibility. To test whether
      endogenous CaM has a function in excitation, trifluoperazine was pressure
      injected into the rhabdomeric region. The response to brief flashes was not
      affected, but the response to steady illumination was transiently attenuated by
      each injection. We conclude that calmodulin should be considered a candidate to
      couple intermediate and late stages of the transduction cascade.

PMID- 16904827
TI  - Histogranin reduced brain injury after transient focal ischemia in rats.
AB  - Excitatory amino acids (EAAs) play an important role during ischemic brain
      injury. In this study we examined the protective effect of histogranin (HN), an
      endogenous peptide that antagonizes excitatory amino acids-mediated activity
      noncompetitively, in an animal model of cerebral ischemia. Adult rats were
      anesthetized with chloral hydrate. Histogranin was given
      intracerebroventricularly before a 60-min middle cerebral artery occlusion
      (MCAo). Animals were examined for their locomotor activity 2 days after MCAo.
      Histogranin significantly increased locomotor activity in the stroke rats.
      Histogranin pretreatment reduced the volume of cerebral infarction and the
      caspase-3 immunoreactivity in the stroke animals. Taken together, our data
      suggest that histogranin is protective against ischemic brain injury. The
      protective effect may involve anti-apoptotic mechanisms.

PMID- 16904828
TI  - Apolipoprotein E epsilon4 allele in familial and sporadic Parkinson's disease.
AB  - Parkinson's disease (PD) is the second most common age-related neurodegenerative
      disease after Alzheimer's disease (AD). Common risk factors for both diseases
      have been explored to study potential etiologic interactions between these two
      neurodegenerative disorders. The APOE epsilon4 allele, previously associated with
      AD, has also been associated with risk of PD and with the presence of some
      clinical features in PD patients. However, the role of APOE epsilon4 allele in
      risk of PD remains unclear. We studied the distribution of APOE alleles in 276
      unrelated familial and sporadic PD patients and in 212 controls. Patients and
      controls were classified by ethnicity. No genetic heterogeneity between Basques
      and people from other regions of Spain was found. No significant differences in
      APOE allele distribution between PD patients and controls were found; however,
      lower epsilon4 allele frequency was observed when the sporadic PD group was
      analyzed separately. By contrast, an increase in epsilon4 allele frequency was
      found in familial PD patients with cognitive decline. We conclude that the APOE
      epsilon4 allele may be associated with the risk of developing PD in isolated
      cases and that it is linked to the presence of cognitive decline in familial PD
      in our sample.

PMID- 16904829
TI  - Coping with rheumatoid arthritis pain in daily life: within-person analyses
      reveal hidden vulnerability for the formerly depressed.
AB  - This study examined the association between history of depression and day-to-day
      coping with rheumatoid arthritis (RA) pain. The sample was 188 RA-diagnosed
      participants, 73 of whom were identified by a structured clinical interview as
      having a history of major depression. None had current major depression. All
      participated in a 30-day prospective study in which they made end-of-day ratings
      of their arthritis pain, the strategies for how they coped with their pain, their
      appraisals of daily pain, and daily mood. Hierarchical linear models evaluated
      whether individuals with and without depression history differed in their average
      pain and the other daily measures; and separately, whether they differed in their
      within-person associations between pain and the daily measures (e.g., the day-to
      day contingency between pain and mood). All analyses controlled for current mild
      depressive symptoms, neuroticism, and age. Previously depressed individuals were
      indistinguishable from their never depressed peers in their average pain and the
      other daily measures; however, the previously depressed exhibited significantly
      stronger associations between pain and several aspects of their daily emotional
      experience, suggesting more pain-contingent well-being. For individuals with a
      history of depression, increases in daily pain corresponded with more frequent
      efforts to cope with their pain by venting their emotions, significantly stronger
      impairments in mood, and, if they were also presently distressed, reduced
      perceptions of control over their pain, compared to the never depressed. Patterns
      suggest that formerly depressed individuals exhibit a hidden vulnerability in how
      they manage chronic pain. This vulnerability is best revealed by a daily process
      approach.

PMID- 16904830
TI  - Transport of liposomal and albumin loaded curcumin to living cells: an absorption
      and fluorescence spectroscopic study.
AB  - Curcumin, a lipid soluble antioxidant, exhibits solvent and medium sensitive
      absorption and fluorescence properties. Using such changes, the average binding
      constants of curcumin to phosphatidylcholine (PC) liposomes and human serum
      albumin (HSA) were estimated to be 2.5 x 10(4) M(-1) and 6.1 x 10(4) M(-1)
      respectively. From the studies on temperature dependent fluorescence anisotropy
      of liposomal curcumin and its fluorescence quenching by acrylamide and iodide, it
      was concluded that curcumin is located in the gel phase of the liposomes.
      Similarly from the studies on quenching of tryptophan fluorescence in HSA by
      curcumin, it was found to be in the same domain as that of tryptophan. Both
      liposomal and HSA vehicles were examined for the transfer of curcumin to spleen
      lymphocyte cells, EL4 lymphoma cell line and compared with aqueous DMSO vehicles.
      From these studies it was found that liposomal vehicle is capable of loading more
      curcumin in to cells than HSA or aqueous-DMSO, and lymphoma cells show
      preferential uptake of curcumin to lymphocytes. The fluorescence of curcumin in
      EL4 lymphoma cells was found to be significantly higher as compared to the
      lymphocytes. The present study demonstrates a simple and quantitative method of
      estimation of curcumin delivered to cells by different vehicles using absorption
      and fluorescence spectroscopy.

PMID- 16904831
TI  - Actions of TGF-beta as tumor suppressor and pro-metastatic factor in human
      cancer.
AB  - Transforming growth factor-beta (TGF-beta) is a secreted polypeptide that signals
      via receptor serine/threonine kinases and intracellular Smad effectors. TGF-beta
      inhibits proliferation and induces apoptosis in various cell types, and
      accumulation of loss-of-function mutations in the TGF-beta receptor or Smad genes
      classify the pathway as a tumor suppressor in humans. In addition, various
      oncogenic pathways directly inactivate the TGF-beta receptor-Smad pathway, thus
      favoring tumor growth. On the other hand, all human tumors overproduce TGF-beta
      whose autocrine and paracrine actions promote tumor cell invasiveness and
      metastasis. Accordingly, TGF-beta induces epithelial-mesenchymal transition, a
      differentiation switch that is required for transitory invasiveness of carcinoma
      cells. Tumor-derived TGF-beta acting on stromal fibroblasts remodels the tumor
      matrix and induces expression of mitogenic signals towards the carcinoma cells,
      and upon acting on endothelial cells and pericytes, TGF-beta regulates
      angiogenesis. Finally, TGF-beta suppresses proliferation and differentiation of
      lymphocytes including cytolytic T cells, natural killer cells and macrophages,
      thus preventing immune surveillance of the developing tumor. Current clinical
      approaches aim at establishing novel cancer drugs whose mechanisms target the TGF
      beta pathway. In conclusion, TGF-beta signaling is intimately implicated in tumor
      development and contributes to all cardinal features of tumor cell biology.

PMID- 16904832
TI  - More than two different bacterial species isolated from blood of toxic epidermal
      necrolysis patients significantly increase mortality.

PMID- 16904833
TI  - Acute hypoxia and programmed cell death in developing CNS: Differential
      vulnerability of chick optic tectum layers.
AB  - The chick optic tectum displays an alternating pattern of cellular and plexiform
      layers and at embryonic day (ED) 12 there are mainly four cellular layers:
      transient cell compartment 3 (TCC3), compartment "h-i-j"(C"h-i-j"), stratum
      griseum centrale (SGC) and subventricular zone (SvZ). In the present work we
      characterized the programmed cell death (PCD) of these layers and their
      vulnerability to acute hypoxia at ED12, and also identified the main cellular
      type involved in hypoxic cell death. The colocalization of three independent
      markers of cell degeneration: pyknotic nuclei by Hoechst staining, fragmented DNA
      by TdT-mediated dUTP nick-end labeling (TUNEL), and presence of active caspase-3
      by immunofluorescence, was analyzed in embryos that developed in normoxic
      conditions (control embryos) and embryos that were subjected to hypoxia (8%
      O(2)/92% N(2)) for 60 min (hypoxic embryos), followed by 0-12 h of normoxic
      recovery. In control embryos cell death rate within each layer was constant
      through time, but there were significant differences (P<0.01) in cell death rates
      among the different layers. In contrast, in hypoxic embryos, a significant
      increase (P<0.01) in cell death rate was observed in layers TCC3, C"h-i-j" and
      SGC. This change was evident only at 6 h post-hypoxia, and at later time points
      cell death rate was similar to control values. Each of these layers had a
      different vulnerability to the hypoxic event while the SvZ layer was not
      affected. In addition, the significant colocalization between the neuron specific
      nuclear protein (NeuN) and TUNEL signal showed that hypoxia affected primarily
      neurons. In conclusion, our findings demonstrate that in the chick optic tectum
      at ED12, PCD is layer dependent and that acute hypoxia causes a transient
      increase in neuronal death in a delayed fashion, which is also layer dependent.
      The morphological features of the neuronal death process at the light microscope
      level resembled apoptosis.

PMID- 16904834
TI  - Amyloid beta-protein1-42 increases cAMP and apolipoprotein E levels which are
      inhibited by beta1 and beta2-adrenergic receptor antagonists in mouse primary
      astrocytes.
AB  - Amyloid beta-protein (Abeta) increases apolipoprotein E (apoE) levels in
      astrocytes which could alter lipid trafficking. The mechanism for the Abeta
      induced increase in apoE levels is not well understood. It is well established
      that stimulation of beta-adrenergic receptors (betaARs) increases cAMP levels.
      Elevation of cAMP levels increases apoE abundance. The current study determined
      if Abeta(1-42) stimulation of cAMP and apoE levels could be inhibited by betaAR
      antagonists in astrocytes. We demonstrate that Abeta(1-42) but not the reverse
      protein Abeta(42-1) or Abeta(1-40) stimulated cAMP formation and this stimulation
      was inhibited by selective betaAR antagonists in mouse primary cortical
      astrocytes. Abeta(1-42) significantly increased apoE levels which were
      significantly inhibited by the betaAR selective antagonists with the greatest
      inhibition observed with the beta(2) antagonist. Separate lines of evidence have
      suggested that agonist-induced stimulation of betaARs and increases in apoE
      abundance may serve a neuroprotective role in astrocytes. Our results indicate a
      potential interaction between betaARs and apoE which may contribute to reducing
      Abeta(1-42) neurotoxicity.

PMID- 16904835
TI  - Plasma agouti-related protein levels in women with anorexia nervosa.
AB  - Agouti-related protein (AGRP) is the competitive antagonist of alpha-melanocyte
      stimulating hormone (alpha-MSH) located at melanocortin receptors 3 and 4 (MC3R
      and MC4R), and also acts as an MC4R inverse agonist. Hypothalamic AGRP controls
      food intake and body weight in rodents. It has also been found in human plasma.
      To study the possibility of disturbances in melanocortin receptor-related
      peptides in eating disorders, plasma AGRP, alpha-MSH, and leptin levels were
      measured in 18 female patients with anorexia nervosa (AN) (age, 23.5+/-7.1 yr;
      body mass index (BMI) 14.5+/-1.8 kg/m(2)) and 17 age-matched female controls
      (age, 25.8+/-3.9 yr; BMI 20.2+/-1.6 kg/m(2)). Blood samples were collected after
      overnight fasting, and plasma peptides levels were measured using ELISA. Plasma
      AGRP levels increased significantly in AN patients when compared with controls
      (P<0.01) while plasma alpha-MSH levels were not significantly different. Plasma
      leptin levels decreased significantly in AN patients when compared with controls
      (P<0.001). In addition, plasma AGRP levels were negatively correlated with leptin
      (r=-0.41, P<0.01) and BMI (r=-0.40, P<0.05) in all subjects. In conclusion,
      plasma AGRP elevation may be related to energy homeostasis disturbance in AN, and
      in addition to leptin, peripheral AGRP levels could be used as a nutritional
      marker in AN patients.

PMID- 16904836
TI  - Acute subendocardial ischaemia leads to homogenous prolongation in ventricular
      repolarization.
AB  - Acute transmural ischaemia often shortens ventricular repolarization and
      increases repolarization dispersion, leading to life threatening ventricular
      arrhythmias in animal models and human subjects. Experimental studies and
      clinical observations have shown that acute subendocardial ischaemia rarely
      causes serious ventricular arrhythmia. We hypothesized that the different
      arrhythmia outcomes between transmural and subendocardial ischaemia are largely
      due to the homogenous prolongation in ventricular repolarization after acute
      subendocardial ischaemia. Further experimental studies on a subendocardial model
      are required to assess the changes in ventricular repolarization and its spatial
      dispersion, and to investigate the role of these changes in the pathogenesis of
      ventricular arrhythmias. These studies will facilitate our understanding on the
      mechanisms of life-threatening ventricular arrhythmias during acute myocardial
      ischaemia.

PMID- 16904837
TI  - High-dose simultaneously integrated breast boost using intensity-modulated
      radiotherapy and inverse optimization.
AB  - PURPOSE: Recently a Phase III randomized trial has started comparing a boost of
      16 Gy as part of whole-breast irradiation to a high boost of 26 Gy in young
      women. Our main aim was to develop an efficient simultaneously integrated boost
      (SIB) technique for the high-dose arm of the trial. METHODS AND MATERIALS:
      Treatment planning was performed for 5 left-sided and 5 right-sided tumors. A
      tangential field intensity-modulated radiotherapy technique added to a
      sequentially planned 3-field boost (SEQ) was compared with a simultaneously
      planned technique (SIB) using inverse optimization. Normalized total dose (NTD)
      corrected dose volume histogram parameters were calculated and compared. RESULTS:
      The intended NTD was produced by 31 fractions of 1.66 Gy to the whole breast and
      2.38 Gy to the boost volume. The average volume of the PTV-breast and PTV-boost
      receiving more than 95% of the prescribed dose was 97% or more for both
      techniques. Also, the mean lung dose and mean heart dose did not differ much
      between the techniques, with on average 3.5 Gy and 2.6 Gy for the SEQ and 3.8 Gy
      and 2.6 Gy for the SIB, respectively. However, the SIB resulted in a
      significantly more conformal irradiation of the PTV-boost. The volume of the PTV
      breast, excluding the PTV-boost, receiving a dose higher than 95% of the boost
      dose could be reduced considerably using the SIB as compared with the SEQ from
      129 cc (range, 48-262 cc) to 58 cc (range, 30-102 cc). CONCLUSIONS: A high-dose
      simultaneously integrated breast boost technique has been developed. The unwanted
      excessive dose to the breast was significantly reduced.

PMID- 16904838
TI  - CT appearance of radiation injury of the lung and clinical symptoms after
      stereotactic body radiation therapy (SBRT) for lung cancers: are patients with
      pulmonary emphysema also candidates for SBRT for lung cancers?
AB  - PURPOSE: The purpose of this study was to analyze the computed tomographic (CT)
      appearance of radiation injury to the lung and clinical symptoms after
      stereotactic body radiation therapy (SBRT) and evaluate the difference by the
      presence of pulmonary emphysema (PE) for small lung cancers. METHODS AND
      MATERIALS: In this analysis, 45 patients with 52 primary or metastatic lung
      cancers were enrolled. We evaluated the CT appearance of acute radiation
      pneumonitis (within 6 months) and radiation fibrosis (after 6 months) after SBRT.
      Clinical symptoms were evaluated by Common Terminology Criteria for Adverse
      Events, version 3.0. We also evaluated the relationship between CT appearance,
      clinical symptoms, and PE. RESULTS: CT appearance of acute radiation pneumonitis
      was classified as follows: (1) diffuse consolidation, 38.5%; (2) patchy
      consolidation and ground-glass opacities (GGO), 15.4%; (3) diffuse GGO, 11.5%;
      (4) patchy GGO, 2.0%; (5) no evidence of increasing density, 32.6%. CT appearance
      of radiation fibrosis was classified as follows: (1) modified conventional
      pattern, 61.5%; (2) mass-like pattern, 17.3%; (3) scar-like pattern, 21.2%.
      Patients who were diagnosed with more than Grade 2 pneumonitis showed
      significantly less no evidence of increased density pattern and scar-like pattern
      than any other pattern (p=0.0314, 0.0297, respectively). Significantly, most of
      these patients with no evidence of increased density pattern and scar-like
      pattern had PE (p=0.00038, 0.00044, respectively). CONCLUSION: Computed
      tomographic appearance after SBRT was classified into five patterns of acute
      radiation pneumonitis and three patterns of radiation fibrosis. Our results
      suggest that SBRT can be also safely performed even in patients with PE.

PMID- 16904839
TI  - Gynecologic examination and cervical biopsies after (chemo) radiation for
      cervical cancer to identify patients eligible for salvage surgery.
AB  - PURPOSE: The aim of this study was to evaluate efficacy of gynecologic
      examination under general anesthesia with cervical biopsies after (chemo)
      radiation for cervical cancer to identify patients with residual disease who may
      benefit from salvage surgery. METHODS AND MATERIALS: In a retrospective cohort
      study data of all cervical cancer patients with the International Federation of
      Gynecology and Obstetrics (FIGO) Stage IB1 to IVA treated with (chemo) radiation
      between 1994 and 2001 were analyzed. Patients underwent gynecologic examination
      under anesthesia 8 to 10 weeks after completion of treatment. Cervical biopsy
      samples were taken from patients judged to be operable. In case of residual
      cancer, salvage surgery was performed. RESULTS: Between 1994 and 2001, 169
      consecutive cervical cancer patients received primary (chemo) radiation, of whom
      4 were lost to follow-up. Median age was 56 years (interquartile range [IQR], 44
      71) and median follow-up was 3.5 years (IQR, 1.5-5.9). In each of 111 patients a
      biopsy sample was taken, of which 90 (81%) showed no residual tumor. Vital tumor
      cells were found in 21 of 111 patients (19%). Salvage surgery was performed in 13
      of 21 (62%) patients; of these patients, 5 (38%) achieved long-term, complete
      remission after salvage surgery (median follow-up, 5.2 years; range, 3.9-8.8
      years). All patients with residual disease who did not undergo operation (8/21)
      died of progressive disease. Locoregional control was more often obtained in
      patients who underwent operation (7 of 13) than in patients who were not selected
      for salvage surgery (0 of 8 patients) (p < 0.05). CONCLUSIONS: Gynecologic
      examination under anesthesia 8 to 10 weeks after (chemo) radiation with cervical
      biopsies allows identification of those cervical cancer patients who have
      residual local disease, of whom a small but significant proportion may be
      salvaged by surgery.

PMID- 16904840
TI  - Radioembolization using 90Y-resin microspheres for patients with advanced
      hepatocellular carcinoma.
AB  - PURPOSE: To investigate the antitumor effect of resin microspheres loaded with 90
      yttrium against hepatocellular carcinoma and their safety in the setting of liver
      cirrhosis. PATIENTS AND METHODS: Data from 24 consecutive patients with
      hepatocellular carcinoma (HCC) treated by radioembolization in the period from
      September 2003 to February 2005 were reviewed. Patients received no further
      antineoplastic therapy. A comprehensive evaluation was performed to prevent the
      risk of damage due to microsphere misplacing. Patients were discharged the day
      after microspheres injection. RESULTS: Serious liver toxicity observed among
      cirrhotic patients in a first period was subsequently prevented by modifying the
      selection criteria and the method for calculating the activity to be
      administered. Among 21 patients evaluable for response using Response Evaluation
      Criteria in Solid Tumors (RECIST) criteria, a reduction in size of target lesions
      was observed in all but 1 patient. When considering only target lesions, disease
      control rate and response rate were 100% and 23.8%, respectively. However, 43% of
      patients progressed in the liver in the form of new lesions appearing a median
      time of 3 months after radioembolization. CONCLUSION: Our experience in these
      series of patients indicates that radioembolization using resin microspheres has
      a significant antitumor effect against HCC and that using stringent selection
      criteria and conservative models for calculating the radiation activity to be
      administered, radioembolization can be performed safely even in cirrhotic
      patients.

PMID- 16904841
TI  - Assessing the ability of the antiangiogenic and anticytokine agent thalidomide to
      modulate radiation-induced lung injury.
AB  - PURPOSE: Thalidomide has broad anticytokine properties, which might protect
      normal tissues in patients undergoing chemoradiotherapy. The purpose of this
      study was to determine the maximal tolerated dose of thalidomide when used in
      combination with vinorelbine plus thoracic radiotherapy. METHODS AND MATERIALS:
      Eligible patients had inoperable Stage III non-small-cell lung cancer, a
      Karnofsky Performance Status>or=70, and life expectancy>or=6 months. Patients
      underwent pretreatment evaluation of lung function. Radiotherapy consisted of 66
      Gy in 6.5 weeks. Vinorelbine was administered i.v. (5 mg/m2) 3 times per week
      just before radiotherapy. Thalidomide was begun at 50 mg, p.o., on day 1 of
      chemoradiotherapy and continued once daily for 6 months. Side effects were scored
      using National Cancer Institute Common Toxicity Criteria. RESULTS: Ten patients
      were enrolled. Of the first 6 patients, 2 developed major thrombotic events that
      were believed to be possibly related to thalidomide. The study was suspended and
      modified to require prophylactic anticoagulation. Of the last 4 patients, 2
      developed dose-limiting toxicity attributable to thalidomide; both patients
      required a dose reduction of thalidomide to <50 mg/day. Because the drug is not
      available in an oral product providing <50 mg/day, the study was closed.
      CONCLUSIONS: The combination of thalidomide concurrently with thoracic
      radiotherapy and vinorelbine resulted in excessive toxicity.

PMID- 16904842
TI  - Optimal number of beams for stereotactic body radiotherapy of lung and liver
      lesions.
AB  - PURPOSE: The aim of this study was to determine the optimal number of coplanar
      and noncoplanar external beams in the setting of stereotactic body radiotherapy
      (SBRT). METHODS AND MATERIALS: Spherical targets were delineated within 2
      separate extracranial sites, the lung and liver, with diameters varying from 2 cm
      to 7 cm to cover the range of volumes used in SBRT. Treatment plans were created
      for all target volumes using 5 to 15 geometrically optimized coplanar and
      noncoplanar conformal beams. Dose gradient and normal tissue complication
      probability (NTCP) were evaluated for each set of beam configurations and for
      each target size. RESULTS: For all lung and liver target volumes, the dose
      gradient improved with an increase in beam number from 5 to 15 for both coplanar
      and noncoplanar beam configurations. NTCP decreased as the beam number increased
      from 5 to 9 beams for all target sizes for both coplanar and noncoplanar beams.
      There is no significant improvement in NTCP when more than 9 beams were used for
      treatment planning regardless of target size. CONCLUSION: Based on dosimetric
      criteria, the optimal number of external beams is 13 to 15 for SBRT using either
      coplanar or noncoplanar beam bouquets. Simple biologic models indicate that the
      optimal number of beams is 9 for SBRT of lung and liver lesions >2 cm, whereas
      smaller lesions may benefit from plans using up to 13 beams.

PMID- 16904843
TI  - Survival benefit associated with adjuvant androgen deprivation therapy combined
      with radiotherapy for high- and low-risk patients with nonmetastatic prostate
      cancer.
AB  - BACKGROUND: The use of adjuvant androgen deprivation therapy (ADT) combined with
      radiotherapy has become common in low-risk patients, although clinical trials
      have focused primarily on high-risk patients. This study examines the
      effectiveness of adjuvant ADT combined with radiotherapy for a wide range of
      patients treated in the 1990s. METHODS AND MATERIALS: Prostate cancer survival
      was examined in a population based cohort of 31,643 patients aged 65 to 85 years
      who were diagnosed with nonmetastatic prostate cancer and treated with external
      beam radiotherapy and/or brachytherapy. Instrumental variable analysis methods
      were used to control for selection bias. RESULTS: Patients with stage T3/T4
      disease who received adjuvant ADT experienced improved 5-year and 8-year
      survival. No survival advantage was observed for men with T1/T2 disease during
      this interval. CONCLUSION: High-risk patients who receive primary radiotherapy
      have benefited from adjuvant ADT, whereas low-risk patients with disease confined
      to the prostate have not yet benefited from adjuvant therapy within the first 8
      years after treatment. These findings are consistent with practice guidelines,
      which recommend adjuvant ADT for patients with high-risk disease.

PMID- 16904844
TI  - Antisense inhibition of cyclin D1 expression is equivalent to flavopiridol for
      radiosensitization of zebrafish embryos.
AB  - PURPOSE: Flavopiridol, a small molecule pan-cyclin inhibitor, has been shown to
      enhance the radiation response of tumor cells both in vitro and in vivo. The
      clinical utility of flavopiridol, however, is limited by toxicity, previously
      attributed to pleiotropic inhibitory effects on several targets affecting
      multiple signal transduction pathways. Here we used zebrafish embryos to
      investigate radiosensitizing effects of flavopiridol in normal tissues. METHODS
      AND MATERIALS: Zebrafish embryos at the 1- to 4-cell stage were treated with 500
      nM flavopiridol or injected with 0.5 pmol antisense hydroxylprolyl-phosphono
      nucleic acid oligomers to reduce cyclin D1 expression, then subjected to ionizing
      radiation (IR) or no radiation. RESULTS: Flavopiridol-treated embryos
      demonstrated a twofold increase in mortality after exposure to 40 Gy by 96 hpf
      and developed distinct radiation-induced defects in midline development
      (designated as the "curly up" phenotype) at higher rates when compared with
      embryos receiving IR only. Cyclin D1-deficient embryos had virtually identical IR
      sensitivity profiles when compared with embryos treated with flavopiridol. This
      was particularly evident for the IR-induced curly up phenotype, which was greatly
      exacerbated by both flavopriridol and cyclin D1 downregulation. CONCLUSIONS:
      Treatment of zebrafish embryos with flavopiridol enhanced radiation sensitivity
      of zebrafish embryos to a degree that was very similar to that associated with
      downregulation of cyclin D1 expression. These results are consistent with the
      hypothesis that inhibition of cyclin D1 is sufficient to account for the
      radiosensitizing action of flavopiridol in the zebrafish embryo vertebrate model.

PMID- 16904845
TI  - Dose as a function of liver volume and planning target volume in helical
      tomotherapy, intensity-modulated radiation therapy-based stereotactic body
      radiation therapy for hepatic metastasis.
AB  - PURPOSE: Stereotactic body radiation therapy (SBRT) has been shown to be an
      effective, well-tolerated treatment for local control of tumors metastatic to the
      liver. Multi-institutional Phase II trials are examining 60 Gy in 3 fractions
      delivered by linac-based, 3D-conformal IMRT. HiArt Helical TomoTherapy is a
      treatment unit that delivers co-planar helical IMRT that is capable of image
      guided SBRT. We hypothesized that the maximum tolerable dose (MTD) delivered to a
      lesion by Helical TomoTherapy-based SBRT could be predicted based on the planning
      target volume (PTV) and liver volume. METHODS AND MATERIALS: To test this, we
      performed inverse treatment planning and analyzed the dosimetry for multiple
      hypothetical liver gross tumor volumes (GTV) with conventional PTV expansions.
      Inverse planning was carried out to find the maximum tolerated SBRT dose up to 60
      Gy to be delivered in 3 fractions based on the dose constraint that 700 cc of
      normal liver would receive less than 15 Gy. RESULTS: Regression analysis
      indicated a linear relationship between the MTD, the PTV and the liver volume,
      supporting our hypothesis. A predictive equation was generated, which was found
      to have an accuracy of +/-3 Gy. In addition, dose constraints based on proximity
      to other normal tissues were tested. Inverse planning for PTVs located at varying
      distances from the heart, small bowel, and spinal cord revealed a predictable
      decrease in the MTD as the PTV increased in size or approached normal organs.
      CONCLUSIONS: These data provide a framework for predicting the likely MTD for
      patients considered for Helical TomoTherapy liver SBRT.

PMID- 16904847
TI  - Five-year survivors of brain metastases: a single-institution report of 32
      patients.
AB  - PURPOSE: To report on 32 patients who survived > or = 5 years from brain
      metastases treated at a single institution. METHODS AND MATERIALS: The records of
      1288 patients diagnosed with brain metastases between 1973 and 1999 were
      reviewed. Patients were treated with whole-brain radiation therapy (WBRT),
      surgery, and/or stereotactic radiosurgery (SRS). Thirty-two (2.5%) > or = 5-year
      survivors were identified. Factors contributing to long-term survival were
      identified. RESULTS: Median survival was 9.3 years for > or = 5-year survivors.
      Seven of these patients lived > or = 10 years. Female gender was the only patient
      characteristic that correlated with better survival (p = 0.0369). When these
      patients were compared with < 5-year survivors, age < 65 years (p = 0.0044),
      control of the primary at diagnosis (p = 0.0052), no systemic disease (p =
      0.0012), recursive partitioning analysis (RPA) Class 1 (p = 0.0002 with Class 2;
      p = 0.0022 with Class 3), and single brain metastasis (p = 0.0018) were
      associated with long-term survival in the univariate logistic regression model.
      In the multivariate model, RPA Class 1 compared with Class 2 (OR = 0.39, p =
      0.0196), surgery (OR = 0.16, p < 0.0001), and SRS (OR = 0.41, p = 0.0188) were
      associated with long-term survival. CONCLUSIONS: For patients with good
      prognostic factors such as young age, good RPA characteristics and single
      metastasis, treatment with surgery or SRS offers the best chance for long-term
      survival.

PMID- 16904846
TI  - Five-year prospective patient evaluation of bladder and bowel symptoms after dose
      escalated radiotherapy for prostate cancer with the BeamCath technique.
AB  - PURPOSE: Late side effects were prospectively evaluated up to 5 years after dose
      escalated external beam radiotherapy (EBRT) and were compared with a previously
      treated series with conventional conformal technique. METHODS AND MATERIALS:
      Bladder and bowel symptoms were prospectively evaluated with the Prostate Cancer
      Symptom Scale (PCSS) questionnaire up to 5 years posttreatment. In all, 257
      patients completed the questionnaire 5 years posttreatment. A total of 168
      patients were treated with the conformal technique at doses<71 Gy, and 195 were
      treated with the dose-escalated stereotactic BeamCath technique comprising three
      dose levels: 74 Gy (n=68), 76 Gy (n=74), and 78 Gy (n=53). RESULTS: For all dose
      groups analyzed together, 5 years after treatment, urinary starting problems
      decreased and urinary incontinence increased in comparison to baseline values. No
      increase in other bladder symptoms or frequency was detected. When comparing dose
      groups after 5 years, both the 74-Gy and 78-Gy groups reported increased urinary
      starting problems compared with patients given the conventional dose (<71 Gy). No
      increased incontinence was seen in the 76-Gy or the 78-Gy groups. Bowel symptoms
      were slightly increased during the follow-up period in comparison to baseline.
      Dose escalation with stereotactic EBRT (74-78 Gy) did not increase
      gastrointestinal late side effects after 5 years in comparison to doses<71 Gy.
      CONCLUSION: Dose-escalated EBRT with the BeamCath technique with doses up to 78
      Gy is tolerable, and the toxicity profile is similar to that observed with
      conventional doses<71 Gy.

PMID- 16904849
TI  - The metabolic syndrome.
AB  - The metabolic syndrome (MS) is a cluster of metabolic abnormalities leading to
      increased risk for cardiovascular diseases and diabetes type 2. Its prevalence is
      increasing with aging. There exists actually an epidemic of MS. Visceral obesity
      and the resulting insulin resistance (IR) are the major determinant in the
      development of the MS. Abdominal obesity results in a low grade inflammation via
      the adipose tissue and macrophages secreted adipokines. This inflammation, via
      the generated pro-inflammatory molecules, interferes with the normal insulin
      signalling and thus contributes to the etiopathogenesis of the MS. Large clinical
      studies showed that CRP is increased in obese subjects and concomitantly to the
      number of existing component of the MS. Treatment of the MS is aimed to improve
      the IR by lifestyle changes including exercise and diet alone or in combination
      with medication targeting the individual components but having also anti
      inflammatory actions. More research is needed to bring new therapies to be able
      to decrease the incidence and prevalence of the MS among the population and thus
      increasing their quality of life.

PMID- 16904848
TI  - JAK2, the JAK2 V617F mutant and cytokine receptors.
AB  - Recently, a unique recurrent somatic mutation was identified as a major molecular
      event in polycythemia vera, essential thrombocythemia and idiopathic
      myelofibrosis. Expression of this mutant in cytokine-dependent hematopoietic cell
      lines induces autonomous growth. This effect is enhanced by overexpression of
      cytokine receptors, and can be inhibited by co-expression at higher levels of the
      wild type JAK2, which may compete for a limited pool of receptors. In JAK2
      deficient cells, we showed that JAK2 V617F can transmit signals from ligand
      activated TpoR or EpoR. Furthermore, the mutant JAK2 can be demonstrated to
      stimulate traffic of the EpoR. Thus, JAK2 V617F mutant must be able to interact
      via its intact FERM-SH2 domains with the cytosolic domains of cytokine receptors.
      A synergy between JAK2 V617F and insulin-like growth factor 1 receptor (IGF1R)
      can be detected in cytokine-dependent cell proliferation. Once cells are rendered
      autonomous by expression of JAK2 V617F, IGF1 acquires the ability to activate the
      JAK-STAT pathway. Thus, expression of JAK2 V617F may explain the described
      hypersensitivity of PV erythroid progenitors to IGF1. The V617 is conserved in
      two other mammalian JAKs, JAK1 and Tyk2. The homologous mutants JAK1 V658F and
      Tyk2 V678F are also active in proliferation and transcriptional assays. Such
      mutants may be found in human cancers or autoimmune diseases. In contrast, the
      JAK3 M592F does not lead to activation of JAK3. Current hypotheses on how JAK2
      V617F contributes to three myeloproliferative diseases, and which other events
      may favor one disease versus another, are discussed.

PMID- 16904850
TI  - Simulation of habituation to simple and multiple stimuli.
AB  - Within the psychological literature there are a number of models that reproduce
      the defining properties of habituation to a single stimulus. However, most of
      them do not reproduce the phenomenon of dishabituation shown in empirical
      studies, consisting in the recovery of a stimulus previously habituated upon the
      appearance of a novel stimulus. The present work offers a model of habituation
      which, in addition to reproducing the basic properties of habituation to a
      stimulus, also does so when more than one stimulus is presented, and thus
      includes the dishabituation phenomenon. This model consists of two functions, one
      called "activation" and the other "availability", and is tested by means of
      simulation of the responses in the context of different stimulus patterns. The
      results of the simulation show a good qualitative fit to the empirical results on
      the phenomena of habituation, including dishabituation. In addition, the model is
      suitable for inclusion in associative models that reproduce classical
      conditioning, which will make it possible in the future to incorporate into these
      in a simple way the influence that the habituation of each stimulus may have on
      its association with other stimuli.

PMID- 16904851
TI  - Epidemiological survey of viral diseases of pigs in the Mekong delta of Vietnam
      between 1999 and 2003.
AB  - In the Mekong delta, backyard pig rearing plays an integral role in recycling
      nutrients in farming systems and generating valuable cash income. However,
      development has been hampered by fatal epizootics of piglets and reproductive
      failure of sows. Diseases are named by symptoms and blindly treated with
      antibiotics. As antibiotics are often ineffectual, involvement of viral diseases
      are suspected. To identify the causative agent, we first sero-surveyed porcine
      reproductive and respiratory syndrome (PRRS) and pseudorabies with 478 sera from
      non-vaccinated pigs collected from backyard farms, state farms and
      slaughterhouses in Can Tho province between 1999 and 2002. Antibodies for PRRS
      were first detected in 2002 in backyard farms and at high prevalence in state
      farms with increased piglet mortality. A few backyard breeder pigs had antibodies
      for pseudorabies in 2000 and 2002. With compulsory classical swine fever (CSF)
      vaccination, we examined the relationship between vaccination and antibodies in
      70 serum samples. Seventy-nine percent of vaccinated breeders had CSF antibodies
      higher than expected with irregular vaccination. Since circulation of CSF virus
      was suspected, isolation was attempted at 10 farms with fatal epizootics between
      2002 and 2003. The viruses were detected at all farms and clustered within
      genogroup 2, despite vaccines corresponding to genogroup 1. This study
      demonstrated virologically/serologically the existence of PRRS, pseudorabies and
      CSF viruses in the Mekong delta of Vietnam. We also identified CSF as a cause of
      piglet mortality that disastrously affected backyard farming. Vaccine
      standardization and proper instructions are needed to simplify diagnosis and
      complement established simultaneous vaccination of sows with piglets.

PMID- 16904852
TI  - Assessment of mucoadhesion by a resonant mirror biosensor.
AB  - The aim of this study was to add knowledge to the existing theories of
      mucoadhesion and to review mucoadhesive polymers based on their ability to form
      non-covalent bonds with mucus glycoprotein. Resonant mirror biosensor was used to
      study the candidate mucoadhesive polymers hydroxypropyl methylcellulose,
      carboxymethylcellulose, Carbopol, hyaluronate, alginate and chitosan. Bovine
      submaxillary mucin was chosen as substrate, representing the major glycosylated
      protein in mucus. For comparison, non-glycosylated bovine serum albumin was used
      as an alternative substrate. The results of this study reveal that there is a
      clear correlation between the ionization state of the polymer, which is dependent
      on the pH of the surrounding environment, and its binding behavior. Ionizable
      polymers need to be in their unionized state to be able to form non-covalent
      bonds with mucus glycoprotein. Acidic polymers display binding behavior only at
      pH around or lower than their corresponding pK(a) values and basic polymers vice
      versa. Chitosan was found to be the most mucoadhesive polymer. Unionizable
      polymers like hydroxypropyl methylcellulose did not display any affinity for
      mucus glycoprotein. Unionized amino- and carboxyl groups on polymers were found
      to be important structural feature of polymer for the formation of weak chemical
      bonds to mucus glycoproteins.

PMID- 16904853
TI  - Salicylate induced tinnitus: behavioral measures and neural activity in auditory
      cortex of awake rats.
AB  - Neurophysiological studies of salicylate-induced tinnitus have generally been
      carried out under anesthesia, a condition that abolishes the perception of
      tinnitus and depresses neural activity. To overcome these limitations,
      measurement of salicylate induced tinnitus were obtained from rats using schedule
      induced polydipsia avoidance conditioning (SIPAC) and gap pre-pulse inhibition of
      acoustic startle (GPIAS). Both behavioral measures indicated that tinnitus was
      present after treatment with 150 and 250 mg/kg of salicylate; measurements with
      GPIAS indicated that the pitch of the tinnitus was near 16 kHz. Chronically
      implanted microwire electrode arrays were used to monitor the local field
      potentials and spontaneous discharge rate from multiunit clusters in the auditory
      cortex of awake rats before and after treatment with 150 mg/kg of salicylate. The
      amplitude of the local field potential elicited with 60 dB SPL tone bursts
      increased significantly 2h after salicylate treatment particularly at 16-20 kHz;
      frequencies associated with the tinnitus pitch. Field potential amplitudes had
      largely recovered 1-2 days post-salicylate when behavioral results showed that
      tinnitus was absent. The mean spontaneous spike recorded from the same multiunit
      cluster pre- and post-salicylate decreased from 22 spikes/s before treatment to
      14 spikes/s 2h post-salicylate and recovered 1 day post-treatment. These
      preliminary physiology data suggest that salicylate induced tinnitus is
      associated with sound evoked hyperactivity in auditory cortex and spontaneous
      hypoactivity.

PMID- 16904854
TI  - Non-destructive testing techniques for the forensic engineering investigation of
      reinforced concrete buildings.
AB  - This study describes in detail the results of a laboratory investigation where
      the compressive strength of 150mm side-length cubes was evaluated. Non
      destructive testing (NDT) was carried out using ultrasonic pulse velocity (UPV)
      and impact rebound hammer (IRH) techniques to establish a correlation with the
      compressive strengths of compression tests. To adapt the Schmidt hammer apparatus
      and the ultrasonic pulse velocity tester to the type of concrete used in Algeria,
      concrete mix proportions that are recommended by the Algerian code were chosen.
      The resulting correlation curve for each test is obtained by changing the level
      of compaction, water/cement ratio and concrete age of specimens. Unlike other
      works, the research highlights the significant effect of formwork material on
      surface hardness of concrete where two different mould materials for specimens
      were used (plastic and wood). A combined method for the above two tests, reveals
      an improvement in the strength estimation of concrete. The latter shows more
      improvement by including the concrete density. The resulting calibration curves
      for strength estimation were compared with others from previous published
      literature.

PMID- 16904855
TI  - Endoscopic evaluation of dynamic narrowing of the pharynx by the Bernouilli
      effect producing maneuver in patients with obstructive sleep apnea syndrome.
AB  - OBJECTIVE: To evaluate the dynamic narrowing of the retropalatal pharynx by the
      Bernouilli effect producing maneuver (BEPM) in patients with obstructive sleep
      apnea syndrome (OSAS) with computer-assisted analysis of nasopharyngoscopic
      images. METHODS: Endoscopic images of the retropalatal pharynx were obtained and
      their area was measured by NIH imaging. Because changes in distance between the
      CCD camera of the nasopharyngoscope and the site of pharyngeal narrowing
      decreased the measurement reliability, the area of the retropalatal pharynx was
      divided by the square of the uvula's lateral side length for normalization. We
      calculated both normalized areas: the pharyngeal narrowing during quiet nasal
      breathing and that during BEPM, which is a forced inspiration through the nose
      with the mouth closed. The narrowing rate was then calculated as an index of the
      pharyngeal dynamics. RESULTS: Nasopharyngoscopy combined with BEPM showed a
      medial motion of the lateral walls of the pharynx due to the Bernoulli effect,
      which is an increase in speed and a reduction in pressure of a moving gas passing
      through a tube constriction. There was a significant correlation between the
      narrowing rate of the retropalatal pharynx and the apnea index. The decrease in
      intraluminal pressure at the narrowing combined with the higher atmospheric
      pressure exercised on the lateral pharyngeal walls would induce the pharyngeal
      collapse. There was also a significant correlation between the normalized
      retropalatal are and the apnea index. CONCLUSION: Nasopharyngoscopy with BEPM
      suggest that in addition to the static narrowing, the dynamic narrowing of the
      retropalatal pharynx contributes to the pathophysiology of OSAS. The correlation
      between the apnea index and both the normalized retropalatal area and the
      narrowing rate of the retropalatal pharynx due to the Bernoulli effect constitute
      a quantitative and predictive alternative to the evaluation and understanding of
      the upper airways changes in OSAS.

PMID- 16904856
TI  - Reply to T.U. Hoogenraad's paper published last April. Zinc therapy in Wilson's
      disease.

PMID- 16904857
TI  - Phylogenetic analysis of enteric species of the family Enterobacteriaceae using
      the oriC-locus.
AB  - Phylogenetic analysis of 38 enteric species belonging to the Enterobacteraceae
      family was carried out using the non-coding locus oriC, the chromosomal
      replication origin. The oriC loci were amplified with conserved oligonucleotides
      and the PCR fragments were sequenced directly. The results establish a
      phylogenetic tree for the classification of different species of the genera
      Escherichia, Shigella, Salmonella, Enterobacter, Citrobacter, Klebsiella,
      Raoultella, Kluyvera, Cedecea and Buttiauxella. Functional important protein
      binding sites located in oriC are well conserved throughout the enteric group.
      More over, due to a high overall divergence value phylogenetic trees were robust
      and well supported by bootstrap analysis. In comparison with 16S rDNA analysis,
      the oriC sequences indicated a greater evolutionary divergence for bacteria. We
      propose that the oriC locus might be a suitable phylogenetic marker for the
      identification and classification of bacteria, in particular for closely related
      species.

PMID- 16904858
TI  - Texturising by phase separation.
AB  - The most common food processing operations, thermal and mechanical treatments,
      both affect phase state and texture of foods. The phase separation threshold for
      food biopolymer mixtures is usually below their concentrations characteristically
      found in food. Phase-separation underpins texturisation processes during food
      processing and digestion. The distribution of water between the phases, the
      adsorption of lipids between the phases, the deformation of dispersed particles
      in flowing water-in-water emulsions and the gelation of the phases result in the
      specific morphology and texture of food. A historical experience in texturisation
      includes the development of cooked food and texturized vegetable analogues of
      animal foods.

PMID- 16904859
TI  - Evaluation of a visit preparation intervention implemented in two rural,
      underserved counties of Northern California.
AB  - OBJECTIVE: Evaluate satisfaction with visit preparation at three rural resource
      center sites. METHODS: The resource centers sent eight employees and two
      volunteers for training at UCSF in Consultation Planning (CP). CP is a service to
      help patients make a list of questions before seeing their doctors. Researchers
      used multivariate ordered logistic regression analysis to investigate the
      variation in satisfaction among 99 CP Clients served by the resource centers in
      2003. RESULTS: Sixty-seven CP Clients who completed surveys were highly satisfied
      (mean=8.67, standard deviation (S.D.)=1.85, range=5-10). Variation in
      satisfaction was associated only with whether or not the CP Provider was a breast
      cancer survivor serving a breast patient (p=0.005). Satisfaction was not
      associated with CP Client demographics; type of upcoming medical visit; or CP
      Provider age, remuneration status, nursing background, and volume of CP Clients.
      CONCLUSION: Community-based resource centers have implemented CP to the
      satisfaction of their clients. Further research should expand the delivery of CP
      to more underserved members of the community and evaluate its acceptability and
      impact. There may be a therapeutic alliance formed when survivors provide CP to
      newly diagnosed patients. PRACTICE IMPLICATIONS: CP should be considered by
      patient support programs wishing to expand their client services to include visit
      preparation.

PMID- 16904860
TI  - Progress in the preoperative diagnosis of thyroid nodules: managing uncertainties
      and the ultimate role for molecular investigation.
AB  - The preoperative evaluation of thyroid nodules currently relies on a clinical
      assessment of risk factors and an algorithm based on imprecise tests. With serum
      TSH, thyroid ultrasound and fine-needle aspiration (FNA) with or without
      ultrasound guide, accounting for the routine initial evaluation, indeterminate
      aspirates remain the major obstacle for confidently advising patients whether to
      have surgery or not. Recent clinical guidelines have attempted to settle various
      controversies but many inherent errors of clinical testing result in delayed
      diagnosis and unnecessary surgery. A better solution may ultimately involve the
      use of molecular markers of thyroid carcinogenesis but further research is still
      needed regarding the basic biology of thyroid cancer.

PMID- 16904861
TI  - Ambulatory blood pressure monitoring and endothelium-dependent vasodilation in
      the elderly athletes.
AB  - AIM: Regular exercise is a key component of cardiovascular risk prevention
      strategies, because it is associated with a variety of beneficial metabolic and
      vascular effects that reduce mortality and the incidence of cardiovascular
      adverse events. Endothelium plays an important role in the local regulation of
      vascular tone and structure, mainly by nitric oxide (NO) synthesis and action.
      Aim of the present study was to evaluate in elderly athletes the effect of
      regular aerobic exercise on arterial blood pressure (BP) and on endothelium
      dependent flow-mediated dilation (FMD) of the brachial artery. METHODS: The study
      population included 30 male subjects (mean age 65.6+/-5.6 years), who had
      practiced endurance running at a competitive level for at least 40 years, and 28
      age- and sex-matched subjects (mean age 64.5+/-4.5 years) with sedentary
      lifestyle and free of cardiovascular disease. Athletes and control subjects
      underwent standard 12-lead ECG, clinic BP, 24-h ambulatory BP monitoring and
      endothelium-dependent FMD and endothelium-independent response to glyceryl
      trinitrate (GTN), 400 microg, in the brachial artery by high-resolution
      ultrasonography. RESULTS: Systolic clinic and ambulatory 24-h BP were
      significantly lower in the athletes, than in the controls (P<0.001,
      respectively). Systolic and diastolic 24-h BP variability, when assessed either
      by the standard deviation (S.D.), or by the coefficient of variation (CV), were
      also significantly lower in the athletes (P<0.01). The athletes also had a lower
      24-h, day-time and night-time heart rate (HR) (P<0.01), as well as a lower HR
      variability (P<0.01). As regards circadian BP change, the %Delta was
      statistically significant greater in athletes (P<0.05). Elderly athletes showed
      higher FMD than elderly sedentary subjects (P<0.001), whereas no differences were
      shown in the response to GTN. CONCLUSIONS: Our results, suggest that long-term
      physical activity can counteract the age-related endothelial dysfunction that
      characterizes sedentary aging, preserving the capacity of the endothelium
      dependent vasodilation and reduces BP values improving arterial pressure control.

PMID- 16904862
TI  - Standardized assessment of cognitive functioning during development and aging
      using an automated touchscreen battery.
AB  - This study examined the effects of age, gender and education on subjects spanning
      nine decades on a new cognitive battery of 12 tests. One thousand and seven
      participants between 6 and 82 completed the battery under standardized conditions
      using an automated, computerized touchscreen. Sensitive indicators of change were
      obtained on measures of attention and working memory, learning and memory
      retrieval, and language, visuospatial function, sensori-motor and executive
      function. Improvement tended to occur through to the third and fourth decade of
      life, followed by gradual decrement and/or stabilized performance thereafter.
      Gender differences were obtained on measures of sustained attention, verbal
      learning and memory, visuospatial processing and dexterity. Years of education in
      adults was reflected in performance on measures of verbal function. Overall, the
      test battery provided sensitive indicators on a range of cognitive functions
      suitable for the assessment of abnormal cognition, the evaluation of treatment
      effects and for longitudinal case management.

PMID- 16904863
TI  - Genomic profiling of cortical neurons following exposure to beta-amyloid.
AB  - In vitro and in vivo studies have shown that beta-amyloid peptide induces
      neuronal cell death. To explore the molecular basis underlying beta-amyloid
      induced toxicity, we analyzed gene expression profiles of cultured rat cortical
      neurons treated for 24 and 48 h with synthetic beta-amyloid peptide. From the
      8740 genes interrogated by oligonucleotide microarray analysis, 241 genes were
      found to be differentially expressed and segregated into distinct clusters.
      Functional clustering based on gene ontologies showed coordinated expression of
      genes with common biological functions and metabolic pathways. The comparison
      with genes differentially expressed in cerebellar granule neurons following serum
      and potassium deprivation indicates the existence of common regulatory mechanisms
      underlying neuronal cell death. Our results offer a genomic view of the changes
      that accompany beta-amyloid-induced neurodegeneration.

PMID- 16904864
TI  - Computer-based spelling instruction for students with developmental disabilities.
AB  - Learning to spell on the computer may lead to functionally useful writing skills.
      Alan and Suzy, teenagers with developmental disabilities, were already proficient
      on a variety of naming and matching tasks but had difficulties spelling; Suzy
      also made errors reading orally. In Experiment 1, computer teaching led to new
      anagram and written spelling performances. Suzy's reading also improved. On
      tabletop tasks, Alan and Suzy sorted and retrieved objects to a list they wrote
      and read aloud. When the tabletop tasks were repeated weeks later, Alan's
      spelling accuracy declined but Suzy's was nearly perfect. In Experiment 2, using
      a different and refined teaching format, Alan relearned his old words and Suzy
      learned to spell new words. Immediately afterwards, and weeks later, both Alan
      and Suzy performed nearly perfectly on the tabletop matching, sorting, and
      reading tasks. The results replicate previous research and extend it with a
      refined package of computer methods that establishes durable and potentially
      functional writing skills. The possibility that learning to spell also improves
      oral reading is worthy of further research.

PMID- 16904865
TI  - Methylmercury and neurodevelopment: longitudinal analysis of the Seychelles child
      development cohort.
AB  - BACKGROUND: The Seychelles Child Development Study (SCDS) has been longitudinally
      following a cohort of over 700 children enrolled in 1989. Their mothers consumed
      a diet high in fish during pregnancy. Repeated examination of the SCDS cohort at
      six different ages through age 11 years has shown no pattern of adverse effects.
      Some early appearing beneficial associations between both prenatal and postnatal
      hair MeHg and several child development endpoints were noted. We hypothesized
      these might be related to micronutrients in the fish, but they were not found
      when the children reached middle school age. These findings suggest that the
      associations observed between MeHg and developmental outcomes may vary with
      developmental stage. METHOD: We examined the main cohort of the SCDS to determine
      if this might be true using a longitudinal multiple regression analysis design
      that focused on those endpoints that were repeatedly measured at different ages.
      The primary endpoint analyzed was global cognition, involving a measure of
      developmental quotient or IQ. Secondary analyses included other domains such as
      Reading and Mathematics scholastic achievement, social behavior, and memory.
      Analyses involved two different approaches, one including incorporation of a
      passage of time variable, the other including a difference of scores across time
      points. RESULTS: No significant associations were found between prenatal MeHg
      exposure and any of the repeatedly measured endpoints. CONCLUSIONS: These results
      suggest that even when individual subject variance is controlled there was no
      consistent pattern of associations between child development outcomes and
      prenatal exposures to MeHg from maternal consumption of a diet high in fish. The
      Seychellois diet contains about 10 times more ocean fish than is typically
      consumed by US citizens. Our primary focus on IQ should further inform growing
      scientific interest in the analysis of the risks and benefits of fish consumption
      on overall cognitive ability.

PMID- 16904867
TI  - Sensitivity of elastic properties to measurement uncertainties in laryngeal
      muscles with implications for voice fundamental frequency prediction.
AB  - This paper discusses the effects of measurement uncertainties when calculating
      elastic moduli of laryngeal tissue. Small dimensions coupled with highly
      nonlinear elastic properties exacerbate the uncertainties. The sensitivity of
      both tangent and secant Young's Modulus was quantified in terms of the
      coefficient of variation, which depended on measurement of reference length and
      cross-sectional area. Uncertainties in the measurement of mass, used to calculate
      cross-sectional area of a small tissue sample, affected Young's Modulus
      calculations when tissue absorption of the hydrating solution was not accounted
      for. Uncertainty in reference length had twice the effect on elasticity than
      other measures. The implication of these measurement errors on predicted
      fundamental frequency of vocalization is discussed. Refinements on isolated
      muscle experimental protocols are proposed that pay greatest attention to
      measures of highest sensitivity.

PMID- 16904866
TI  - Ethanol-dependent toxicity in zebrafish is partially attenuated by antioxidants.
AB  - Ethanol is a well-established developmental toxicant; however, the molecular and
      cellular mechanism(s) of toxicity remains unclear. It has been suggested that
      ethanol metabolism leads to oxidative stress resulting in an increase in cell
      death. Alcohol developmental toxicity has not been well studied in zebrafish;
      however, zebrafish represent an excellent vertebrate model for investigating and
      understanding normal and aberrant development. To evaluate ethanol metabolism
      dependent toxicity, chemical inhibitors of the ethanol metabolizing enzymes were
      utilized. Embryos co-exposed to ethanol and a combination of ethanol metabolism
      inhibitors led to a significant increase in the occurrence of pericardial edema.
      Further, in the presence of the inhibitor mixture there was an increase in
      developmental malformations at lower ethanol concentrations. Cell death has been
      implicated as a potential explanation for ethanol-dependent toxicity. Using cell
      death assays, ethanol significantly increased embryonic cell death. To determine
      if oxidative stress underlies cardiovascular dysfunction, embryos were co-exposed
      to ethanol and several antioxidants. The antioxidants, glutathione and lipoic
      acid, partially attenuated the incidence of pericardial edema. The effectiveness
      of the antioxidants to protect the embryos from ethanol-induced cell death was
      also evaluated. The antioxidants provided no protection against cell death. Thus,
      ethanol-mediated pericardial edema and cell death appear to be mechanistically
      distinct.

PMID- 16904868
TI  - Motion compensation in digital subtraction angiography using graphics hardware.
AB  - An inherent disadvantage of digital subtraction angiography (DSA) is its
      sensitivity to patient motion which causes artifacts in the subtraction images.
      These artifacts could often reduce the diagnostic value of this technique.
      Automated, fast and accurate motion compensation is therefore required. To cope
      with this requirement, we first examine a method explicitly designed to detect
      local motions in DSA. Then, we implement a motion compensation algorithm by means
      of block matching on modern graphics hardware. Both methods search for maximal
      local similarity by evaluating a histogram-based measure. In this context, we are
      the first who have mapped an optimizing search strategy on graphics hardware
      while paralleling block matching. Moreover, we provide an innovative method for
      creating histograms on graphics hardware with vertex texturing and frame buffer
      blending. It turns out that both methods can effectively correct the artifacts in
      most case, as the hardware implementation of block matching performs much faster:
      the displacements of two 1024 x 1024 images can be calculated at 3 frames/s with
      integer precision or 2 frames/s with sub-pixel precision. Preliminary clinical
      evaluation indicates that the computation with integer precision could already be
      sufficient.

PMID- 16904869
TI  - Anti-MBL autoantibodies in patients with rheumatoid arthritis: prevalence and
      clinical significance.
AB  - Occurrence of autoantibodies in patients' sera is the characteristic feature of
      autoimmune disorders. We assessed the presence of anti-mannose binding lectin
      (MBL) autoantibodies in the sera of 107 rheumatoid arthritis (RA) patients and
      121 control subjects by enzyme immunoassay. Elevated levels of anti-MBL
      autoantibodies in the sera of RA patients (P<0.0001) was detected for the first
      time. The ratios of anti-MBL positive in RA patients and controls were
      respectively 60.7% and 1.65%. Experiments were then designed to understand the
      functional relevance of these autoantibodies. An inverse correlation of anti-MBL
      autoantibodies with serum MBL levels (P=0.001) and MBL complex activity (P=0.02)
      was observed without genetic association between MBL polymorphisms and anti-MBL
      autoantibody secretion. A significant increase (P=0.038) in the level of anti-MBL
      autoantibodies was observed in 23 synovial fluid samples in comparison to the
      serum samples. Moreover, the anti-MBL autoantibodies were found to be more often
      present in the sera of RA patients (60.75% sensitivity, 98.35% specificity and
      0.913 area under the ROC curve) in comparison to the IgM and IgG isotypes of
      rheumatoid factors (RF). Anti-MBL autoantibodies were still positive in 25.23% RA
      patients when both the RF isotypes were negative. Also, in RA patients, at all
      stages of disease activity and joint deformity, anti-MBL autoantibodies were more
      often present than both the RF isotypes. Therefore, the significant presence of
      anti-MBL autoantibodies enunciates that anti-MBL autoantibodies might have a
      diagnostic value; however, more studies are needed to confirm the role of anti
      MBL autoantibodies in the diagnosis of rheumatoid arthritis.

PMID- 16904870
TI  - IL-2 receptor alpha deficiency and features of primary biliary cirrhosis.
AB  - Congenital immune deficiency states have often been valuable experimental models
      of nature that have significantly enhanced our understanding of the immune
      response. The relationship between CD4+, CD25+ and Treg cells in the induction of
      autoimmunity has attracted significant attention. We report herein a male child
      of consanguineous parents who developed at six months recurrent infections, and
      at age 5 years, liver dysfunction with serological expression of primary biliary
      cirrhosis (PBC), an autoimmune liver disease that usually affects middle-aged
      women. Histologically, there was intense mononuclear cell lymphoid infiltration
      of the intrahepatic portal tracts, CD3+CD4+T cell lymphopenia in blood and serum
      antibody to PDC-E2. Peripheral blood lymphocytes were completely deficient of the
      alpha subunit of the IL-2 receptor (IL-2Ralpha, CD 25), a marker for regulatory T
      cells (Tregs). Allogenic stem cell transplantation led to full recovery. This
      case illustrates the role of deficiency of CD4+CD25+ Treg cells in causing
      autoimmunity, and speaks to the potential use of allogenic stem cell
      transplantation for immunoreconstitution in adult PBC.

PMID- 16904871
TI  - Physical comorbidity, insight, quality of life and global functioning in first
      episode schizophrenia: a 24-month, longitudinal outcome study.
AB  - This prospective study sought to determine the clinical impact of physical
      comorbidity on patients with first episode schizophrenia (FES) and we tested the
      hypothesis that patients with physical comorbidity were associated with poorer
      clinical and functional outcomes. The severity of psychopathology, insight,
      social/occupational functioning and quality of life were evaluated using Positive
      And Negative Syndrome Scale (PANSS), Scale to assess Unawareness of Mental
      Disorder, Global Assessment of Functioning Scale (GAF), and World Health
      Organisation Quality of Life-Bref Scale (WHOQOL-Bref) respectively at baseline
      and at 6, 12, 18 and 24 months. Out of 142 patients, physical comorbidity was
      present in 21.8% (n=31) of the patients, and they were mainly related to the
      cardiovascular, respiratory and endocrine systems. Compared to baseline
      measurements, patients with physical comorbidity had greater awareness into the
      consequences of their psychiatric illness at 12 months, the need for treatment at
      12 and 18 months, and better improvement of PANSS total and general
      psychopathology subscale scores at 24 months. FES patients with physical
      comorbidity also had less reduction in their WHOQOL-Bref scores in the physical
      health domain at 12 and 18 months and greater increase in the GAF scores at 18
      and 24 months, indicating better subjective rating of quality of life and
      objective measure of their global functioning prospectively. Clinicians need to
      be aware of the substantial rates of physical comorbidity in FES patients which
      may not be necessarily associated with worse longitudinal outcomes and the
      findings should encourage even greater efforts at early identification and
      management of these physical conditions.

PMID- 16904872
TI  - Evaluation of antimalarial and fluoroquinolone combinations against Plasmodium
      falciparum in vitro.

PMID- 16904873
TI  - Respiratory tract infections: at-risk patients, who are they? Implications for
      their management with levofloxacin.
AB  - Two of the most serious respiratory tract infections are community-acquired
      pneumonia (CAP) and acute exacerbations of chronic bronchitis (AECB). The most
      common pathogens found in patients with these infections are Haemophilus
      influenzae and Streptococcus pneumoniae. Pseudomonas aeruginosa is also
      relatively common, particularly in elderly patients with AECB. S. pneumoniae and
      P. aeruginosa are also of concern in relation to the development of resistance to
      antimicrobial drugs. The administration of antibiotics at doses that result in
      concentrations exceeding the mutant prevention concentration at the site of
      infection is one strategy to prevent the development of drug-resistant pathogens.
      AECB is associated with a high risk of in-hospital mortality, particularly in
      patients treated in the intensive care unit. CAP is also associated with
      significant risks and often requires treatment under hospital supervision.
      Several patient-related factors help identify those patients who are most at risk
      of mortality and morbidity. Treatment should be tailored towards the severity of
      the disease. The fluoroquinolones, such as levofloxacin, are an effective
      treatment option for AECB and CAP. Compared with many other antibiotics,
      resistance to levofloxacin remains low for most infecting pathogens. The oral
      bioavailability of levofloxacin is over 99%, enabling simple switching from
      intravenous to oral therapy during treatment. It is also preferentially
      distributed to compartments in the lung, thus achieving high concentrations at
      the site of respiratory tract infections. Combined with cover of the major
      infecting pathogens found in patients with AECB and CAP, and a cost-effective
      treatment compared with many alternative therapies, levofloxacin is an attractive
      option for the treatment of at-risk patients with these respiratory tract
      infections.

PMID- 16904874
TI  - Decreasing prevalence of antimicrobial resistance in non-typhoidal Salmonella
      isolated from children with bacteraemia in a rural district hospital, Kenya.
AB  - We analysed 336 non-typhoidal Salmonella (NTS) isolated from children <13 years
      of age with bacteraemia admitted to a rural district hospital in Kenya from 1994
      to 2005. Pulsed-field gel electrophoresis was used to determine genetic
      relatedness of strains, and antimicrobial susceptibility testing was also
      performed. Most NTS were either Salmonella enterica serovar Typhimurium (n=114;
      33.9%) or S. enterica serovar Enteritidis (n=128; 38.1%), with minimal genotypic
      diversity over the study period. The NTS showed a remarkable decrease in levels
      of resistance especially to two commonly available antimicrobials (amoxicillin
      and co-trimoxazole), from high of 69.2% and 68.4% during 1994-1997 to 11% and
      13%, respectively, in 2002-2005 (P<0.01). All NTS remained fully susceptible to
      cefotaxime and ciprofloxacin. Our findings show that commonly available drugs may
      still be useful for treatment of invasive NTS infections in this rural
      population.

PMID- 16904875
TI  - Liver tissue concentrations of levofloxacin after single intravenous
      administration of 500 mg for antibiotic prophylaxis in liver surgery.
AB  - High concentrations of levofloxacin in soft tissues and body fluids, including
      gallbladder and bile, have been repeatedly reported, but no study on its
      penetration into human liver tissue after single-shot application has yet been
      published. Levofloxacin 500 mg was administered intravenously to 28 patients
      scheduled for liver resection. Blood samples were taken after the end of infusion
      and at the time of liver resection; concomitantly, a tissue specimen was also
      obtained. Serum concentrations (mean+/-standard deviation) 10 min after the end
      of infusion were 6.59+/-1.72 microg/mL and decreased only slightly throughout the
      operation. At the time of liver resection, levofloxacin concentrations in liver
      tissue were 18.14+/-5.44 microg/g with corresponding serum concentrations of
      4.84+/-1.37 microg/mL. The tissue/serum ratio (3.72+/-0.73 at the time of
      resection) was nearly constant over the sampling period ranging from 0.4 h to 3.8
      h after the end of infusion, indicating a fast distribution of levofloxacin into
      the liver tissue. The tissue concentrations showed a significant correlation with
      serum concentrations and an inverse correlation with the grade of steatosis but
      not cirrhosis. Infectious post-operative complications were not observed.
      Levofloxacin penetrates into liver tissue exceptionally well and fast and is
      therefore a good candidate for antibiotic prophylaxis before invasive
      hepatobiliary procedures such as liver surgery as well as for treatment of
      biliary tract infections caused by levofloxacin-susceptible microorganisms.

PMID- 16904876
TI  - Nuclear envelope defects in muscular dystrophy.
AB  - Muscular dystrophies are a heterogeneous group of disorders linked to defects in
      20-30 different genes. Mutations in the genes encoding a pair of nuclear envelope
      proteins, emerin and lamin A/C, have been shown to cause the X-linked and
      autosomal forms respectively of Emery-Dreifuss muscular dystrophy. A third form
      of muscular dystrophy, limb girdle muscular dystrophy 1b, has also been linked to
      mutations in the lamin A/C gene. Given that these two genes are ubiquitously
      expressed, a major goal is to determine how they can be associated with tissue
      specific diseases. Recent results suggest that lamin A/C and emerin contribute to
      the maintenance of nuclear envelope structure and at the same time may modulate
      the expression patterns of certain mechanosensitive and stress induced genes.
      Both emerin and lamin A/C may play an important role in the response of cells to
      mechanical stress and in this way may help to maintain muscle cell integrity.

PMID- 16904877
TI  - Comparison of permeation enhancing strategies for an oral factor Xa inhibitor
      using the Caco-2 cell monolayer model.
AB  - FXai, a direct inhibitor of the clotting factor Xa, provides high water
      solubility but poor membrane permeability due to multiple sites of ionization and
      a molecular weight exceeding 500 Da, making it a Class III drug according to the
      Biopharmaceutics Classification System. To overcome the ionization problem and
      increase the transcellular permeability, various ester and hydroxyamidine
      prodrugs exhibiting a reduced number of ionization sites were studied in the Caco
      2 monolayer model for intestinal permeation. Alternatively, the potential
      transcellular permeation enhancement of Imwitor 742 and the potential
      paracellular enhancement of three chitosan formulations were investigated in the
      same model. FXai has an apparent permeability (P(app)) of about 1 nm/s, which is
      generally regarded as very low. The butylester-hydroxyamidine double-prodrug was
      found to provide a markedly increased permeability (40.4 nm/s) as did the co
      application of chitosan (43.3 nm/s). Other prodrugs slightly increased
      permeability (1.3-9.2 nm/s) but were inferior to the previous attempts to enhance
      permeability while the Imwitor admixture showed no effect (1.1 nm/s). Moreover, a
      bioactivating metabolism towards the hydroxyamidine mono-prodrug was detected in
      the Caco-2 cell permeation model. Although esterases were overexpressed and
      mainly located apically, an acceptable permeation was reached. In addition, the
      prodrugs triggered an efflux system that is not inhibited by verapamil but by
      quinidine, suggesting the involvement of an organic cation transporter.

PMID- 16904878
TI  - Safety of ethanolic kava extract: Results of a study of chronic toxicity in rats.
AB  - BACKGROUND: Recently, potential liver toxicity was discussed with the intake of
      kava extract preparations (Piper methysticum) as anxiolytic drugs. The aim of
      this study was to test chronic toxicity in rats by oral application of an
      ethanolic kava full extract. METHODS: Wistar rats of both sexes were fed 7.3 or
      73 mg/kg body weight of ethanolic kava extract for 3 and 6 months. The animals
      were examined for changes in body weight, hematological and liver parameters, and
      macroscopical and microscopical histological changes in the major organs.
      RESULTS: No signs of toxicity could be found. CONCLUSIONS: The results are in
      accordance with the medical experience regarding the use of kava preparations and
      the long tradition of kava drinking in the South Pacific island states.
      Specifically, the results do not back the suspicion of potential liver toxicity.

PMID- 16904879
TI  - Phylogenetic analysis of nuclear small subunit rDNA sequences suggests that the
      endangered African Pencil Cedar, Juniperus procera, is associated with distinct
      members of Glomeraceae.
AB  - The endangered indigenous tree species Juniperus procera, commonly known as
      African Pencil Cedar, is an important component of the dry Afromontane vegetation
      of Ethiopia and was shown to be AM in earlier studies. Here we describe the
      composition of AM fungi in colonized roots of J. procera from two dry Afromontane
      forests of Ethiopia. The nuSSU rDNA gene was amplified from colonized roots,
      cloned and sequenced using AM fungal specific primers that were partly developed
      for this study. Molecular phylogenetic analysis revealed that all the glomeralean
      sequences obtained belonged exclusively to the genus Glomus (Glomeraceae). Seven
      distinct Glomus sequence types were identified that all are new to science. The
      composition of the AM fungal communities between the sampled trees, and between
      the two study sites in general, differed significantly. Isolation and utilization
      of the indigenous AM fungal taxa from the respective sites might be required for
      successful enrichment plantation of this threatened Juniperus species.

PMID- 16904880
TI  - Characterization of fungi from hypersaline environments of solar salterns using
      morphological and molecular techniques.
AB  - The Cabo Rojo Solar Salterns located on the southwest coast of Puerto Rico are
      composed of two main ecosystems (i.e., salt ponds and microbial mats). Even
      though these locations are characterized by high solar radiation (mean light
      intensity of 39 mol photons m-2d-1) they harbour a diverse microscopic life. We
      used morphological and molecular techniques to identify a series of halotolerant
      fungi. A total of 183 isolates and 36 species were cultured in this study. From
      the water from the salt ponds, 86 isolates of 26 species were cultured. The
      halotolerant fungi isolated from water were: Cladosporium cladosporioides, nine
      Aspergillus sp., five Penicillium sp. and the black yeast Hortaea werneckii. A
      distinctive isolate with a blue mycelium was cultured from the salt ponds,
      representing a new species of Periconia based on morphology and rDNA analysis.
      Forty-four isolates from eight species were cultured from the sediments around
      the salt ponds. Most of the sediment isolates formed only sterile mycelium, while
      several were Chaetomium globosum. A total of 53 isolates from 16 species were
      isolated from the three layers of the microbial mats, of which Aspergillus niger
      was the most frequent isolate. Phospholipid fatty acid profiles generated from
      the different layers of the microbial mats indicated that the uppermost layers of
      the mats contained fungal biomarker, 18:2w6. This fatty acid decreased with
      depth, the highest concentration was observed in the green upper layer and it
      disappeared in the black bottom anoxic layer. This correlates with the isolation
      of fungi using the serial dilution technique. This is the first study that
      documents the presence of fungi in microbial mats.

PMID- 16904881
TI  - Genetic linkage between growth rate and the intersterility genes S and P in the
      basidiomycete Heterobasidion annosum s.lat.
AB  - Quantitative trait loci (QTL) for mycelial growth rate were identified and
      positioned on a genetic linkage map of Heterobasidion annosum sensu lato (s.l.),
      an important root rot pathogen on conifers. The mycelial growth rate among 84
      progeny isolates were analysed in two different temperature regimes, 12 and 24
      degrees C on malt extract agar and found to segregate as a continuous character.
      The assay identified three QTL for growth rate at low temperature positioned on
      the linkage groups 1, 17 and 19 with peak LOD values of 3.2, 2.9 and 4.8,
      respectively. At the QTL for high temperature growth, peak LOD values of 1.3, 2.8
      and 2.2, were identified. The three QTL for the low temperature regime explained
      20.9, 18.1 and 24.0 % of the variation in the mycelial growth rate, respectively.
      The broad-sense heritability was estimated to be 0.97 and 0.95 for growth rate at
      low and high temperatures, respectively. Two of the QTL for the mycelial growth
      rate were shown to be tightly linked to the intersterility genes S and P, which
      control mating within and between closely related species and intersterility
      groups of H. annosum s.lat. Isolates with a plus allele at the intersterility
      loci had a higher growth rate than isolates that harboured minus alleles.

PMID- 16904882
TI  - Cryptococcus stepposus, a new filobasidiaceous yeast species found in the
      Prioksko-terrasny biosphere reserve in Russia.
AB  - Mycocinotyping of cryptococci from the Prioksko-terrasny reserve (Russia) has
      revealed three strains that have a unique mycocin-sensitivity profile. Sequencing
      results of the D1/D2 domain of the 26S rDNA and of the complete ITS region placed
      them in the Floriforme clade of the Filobasidiales lineage (Hymenomycetes). The
      three strains had identical sequences, which differed from those of known
      Filobasidium and Cryptococcus species. A novel species named Cryptococcus
      stepposus (type strain VKM Y-2918) is proposed to accommodate these isolates.
      Physiological characteristics distinguishing the novel species from other
      Cryptococcus species in the Floriforme clade are presented.

PMID- 16904883
TI  - Integrin structures and conformational signaling.
AB  - Integrins are cell adhesion molecules that play critical roles in development,
      wound healing, hemostasis, immunity and cancer. Advances in the past two years
      have shed light on the structural basis for integrin regulation and signaling,
      especially on how global conformational changes between bent and extended
      conformations relate to the inter-domain and intra-domain shape shifting that
      regulates affinity for ligand. The downward movements of the C-terminal helices
      of the alpha I and beta I domains and the swing-out of the hybrid domain play
      pivotal roles in integrin conformational signaling. Experiments have also shown
      that integrins transmit bidirectional signals across the plasma membrane by
      coupling extracellular conformational change with an unclasping and separation of
      the alpha and beta transmembrane and cytoplasmic domains.

PMID- 16904885
TI  - An inductive power link for a wireless endoscope.
AB  - An inductive link is presented that can handle freedom of motion. The envisaged
      application is to power a wireless camera capsule used for non-invasive visual
      inspection of the small bowel. Up to 150 mW of usable dc power can be delivered
      to the capsule for the entire duration of its travel along the gastric track. The
      outer dimensions of the power receiver compartment inside the capsule are O 10
      mmx13 mm. The power efficiency of the link is measured to be 1% under worst-case
      geometrical conditions. The issue of patient's health and safety regarding
      exposure to the electromagnetic field is addressed. To this purpose, an
      experimental method is applied to predict specific absorption rates. Conversely,
      the effect of biological tissue on link performance and practical workability is
      evaluated as well. Electric shielding of the transmitter coil is applied to
      reduce biological tissue interaction. In this way, appliance on a living subject
      is made both safe and practically feasible.

PMID- 16904884
TI  - Methane and carbon dioxide emission in a two-phase olive oil mill sludge windrow
      pile during composting.
AB  - The aim of this work was to make some preliminary evaluations on CO(2) and CH(4)
      emissions during composting of two-phase olive oil mill sludge (OOMS). OOMS,
      olive tree leaves (OTL) and shredded olive tree branches (OTB) were used as
      feedstock for Pile I and Pile II with a 1:1:1 and 1:1:2v/v ratio, respectively.
      Each pile was originally 1.2m high, 2.0m wide and approximately 15.0m long. Four
      500 ml volume glass funnels were inverted and introduced in each pile, two in the
      core (buried 50-60 cm from the surface) and two near the surface under a thin 10
      15 cm layer of the mixture. Thin (0.5 cm diameter) plastic, 80 cm long tubes were
      connected to the funnels. A mobile gas analyser (GA2000) was used to measure the
      composition (by volume) of O2, CO2 and CH4 on a daily basis. The funnels were
      removed prior to each turning and reinserted afterwards. From each pair of
      funnels (core and surface) of both piles, one was kept closed between samplings.
      Two way ANOVA was used to test differences between piles and among the tubes.
      Post hoc Tukey tests were also used to further investigate these differences.
      There was a significant difference (at p<0.001) in the two piles for all three
      gases. The average concentrations of O2, CO2 and CH4 in Pile I, from all four
      funnels was 16.86%, 3.89% and 0.25%, respectively, where for Pile II the average
      values were 18.07%, 2.38% and 0.04%, respectively. The presence of OOMS in larger
      amounts in Pile I (resulting in more intense decomposing phenomena), and the
      larger particle size of OTB in Pile II (resulting in increasing porosity) are the
      probable causes of these significant differences. Samples from open funnels
      presented lower, but not significantly lower, O2 composition (higher for CO2 and
      CH4) in comparison with closed funnels in both depths and both piles. Not
      significant were also the different mean gas compositions between core and
      surface funnels in the same pile.

PMID- 16904886
TI  - Amphotericin B channels in phospholipid membrane-coated nanoporous silicon
      surfaces: implications for photovoltaic driving of ions across membranes.
AB  - The antimycotic agent amphotericin B (AmB) functions by forming complexes with
      sterols to form ion channels that cause membrane leakage. When AmB and
      cholesterol mixed at 2:1 ratio were incorporated into phospholipid bilayer
      membranes formed on the tip of patch pipettes, ion channel current fluctuations
      with characteristic open and closed states were observed. These channels were
      also functional in phospholipid membranes formed on nanoporous silicon surfaces.
      Electrophysiological studies of AmB-cholesterol mixtures that were incorporated
      into phospholipid membranes formed on the surface of nanoporous (6.5 nm pore
      diameter) silicon plates revealed large conductance ion channels ( approximately
      300 pS) with distinct open and closed states. Currents through the AmB
      cholesterol channels on nanoporous silicon surfaces can be driven by voltage
      applied via conventional electrical circuits or by photovoltaic electrical
      potential entirely generated when the nanoporous silicon surface is illuminated
      with a narrow laser beam. Electrical recordings made during laser illumination of
      AmB-cholesterol containing membrane-coated nanoporous silicon surfaces revealed
      very large conductance ion channels with distinct open and closed states. Our
      findings indicate that nanoporous silicon surfaces can serve as mediums for ion
      channel-based biosensors. The photovoltaic properties of nanoporous silicon
      surfaces show great promise for making such biosensors addressable via optical
      technologies.

PMID- 16904887
TI  - Immunocytochemical localisation of plasma membrane GHRH receptors in human
      tumours using a novel anti-peptide antibody.
AB  - Antagonists of growth hormone releasing hormone (GHRH) directly inhibit the
      growth of a variety of human neoplasms. However, the plasma membrane receptor
      mediating these effects has not been immunocytochemically visualised in primary
      tumour cells. Given that previous attempts using an antibody to the amino
      terminal region did not result in the visualisation of plasma membrane receptors,
      we have developed and characterised an anti-peptide antibody to the carboxy
      terminal region 403-422 of the human pituitary GHRH receptor. This sequence is
      identical to residues 339-358 of splice variant 1 (SV1) of tumoural GHRH
      receptors. Specificity of the antibody was demonstrated by (1) immunocytochemical
      staining of GHRH receptor-transfected cells, (2) detection of a broad
      glycosylated protein band migrating at Mr 50,000-60,000 in Western blots of
      membranes from human pituitary, and (3) abolition of tissue immunostaining by
      preadsorbtion of the antibody with its immunising peptide. The distribution of
      GHRH receptors was investigated in 69 formalin-fixed, paraffin-embedded human
      tumours showing that GHRH receptors were frequently expressed in breast, ovarian
      and prostate carcinomas. Immunoreactive GHRH receptors were clearly confined to
      the plasma membrane and uniformly present on nearly all tumour cells. In Western
      blots of membranes prepared from human tumours, the anti-GHRH receptor antibody
      detected a non-glycosylated protein band migrating at Mr 40,000, which
      corresponds to the expected molecular weight of splice variant 1 of tumoural GHRH
      receptors. Together, our findings provide direct evidence for the presence of
      GHRH receptor protein on the plasma membrane of primary human tumour cells. The
      GHRH receptor visualisation could be of value for a rapid immunohistochemical
      identification of those tumours which could be a target for diagnostic or
      therapeutic intervention using GHRH analogues.

PMID- 16904888
TI  - Electrical performance analysis and economic evaluation of combined biomass cook
      stove thermoelectric (BITE) generator.
AB  - The use of biomass cook stoves is widespread in the domestic sector of developing
      countries, but the stoves are not efficient. To advance the versatility of the
      cook stove, we investigated the feasibility of adding a commercial thermoelectric
      (TE) module made of bismuth-telluride based materials to the stove's side wall,
      thereby creating a thermoelectric generator system that utilizes a proportion of
      the stove's waste heat. The system, a biomass cook stove thermoelectric generator
      (BITE), consists of a commercial TE module (Taihuaxing model TEP1-1264-3.4), a
      metal sheet wall which acts as one side of the stove's structure and serves as
      the hot side of the TE module, and a rectangular fin heat sink at the cold side
      of the TE module. An experimental set-up was built to evaluate the conversion
      efficiency at various temperature ranges. The experimental set-up revealed that
      the electrical power output and the conversion efficiency depended on the
      temperature difference between the cold and hot sides of the TE module. At a
      temperature difference of approximately 150 degrees C, the unit achieved a power
      output of 2.4W. The conversion efficiency of 3.2% was enough to drive a low power
      incandescent light bulb or a small portable radio. A theoretical model
      approximated the power output at low temperature ranges. An economic analysis
      indicated that the payback period tends to be very short when compared with the
      cost of the same power supplied by batteries. Therefore, the generator design
      formulated here could be used in the domestic sector. The system is not intended
      to compete with primary power sources but serves adequately as an emergency or
      backup source of power.

PMID- 16904889
TI  - Activated carbon briquettes from biomass materials.
AB  - Disposal of biomass wastes, produced in different agricultural activities, is
      frequently an environmental problem. A solution for such situation is the
      recycling of these residues for the production of activated carbon, an adsorbent
      which has several applications, for instance in the elimination of contaminants.
      For some uses, high mechanical strength and good adsorption characteristics are
      required. To achieve this, carbonaceous materials are conformed as pellets or
      briquettes, in a process that involves mixing and pressing of char with adhesive
      materials prior to activation. In this work, the influence of the operation
      conditions on the mechanical and surface properties of briquettes was studied.
      Eucalyptus wood and rice husk from Uruguay were used as lignocellulosic raw
      materials, and concentrated grape must from Cuyo Region-Argentina, as a binder.
      Different wood:rice and solid:binder ratios were used to prepare briquettes in
      order to study their influence on mechanical and surface properties of the final
      products.

PMID- 16904890
TI  - Synthesis of rigid trichostatin A analogs as HDAC inhibitors.
AB  - New inhibitors of histone deacetylase (HDAC) have been synthesized and evaluated
      for their activity toward non small lung cancer cell line H661. Their design is
      based on indanone (or tetralone) systems leading to trichostatin A (TSA) analogs
      with limited conformational mobility. Molecular modelization at the AM1 level
      revealed that the conformations of indane-based analogs and TSA bound to HDAC
      like protein are similar. The synthesis of these new analogs was achieved by
      alkylation of an appropriate indanone (or tetralone) to introduce the side chain
      bearing a terminal ester group, the latter being a precursor of hydroxamic acid
      and aminobenzamide derivatives. Hydroxamic acids with the TSA side chain were
      found to be the most active compounds and the presence of the dimethylamino group
      on the phenyl ring turned out to be essential to achieve low micromolar
      activities against H661 cancer cells.

PMID- 16904891
TI  - Should a standard be defined for the Positive Predictive Value (PPV) of recall in
      the UK NHS Breast Screening Programme?
AB  - The UK NHSBSP defines standards for both cancer detection rate and recall rate
      for assessment but has not explicitly set a defined standard for positive
      predictive value (PPV) of recall. However, as PPV is defined as the percentage of
      women who are recalled and have a final diagnosis of cancer, a standard for PPV
      is an implicit consequence of the standards for cancer detection rate and recall
      rate. The standards are defined in terms of a lower level of acceptability known
      as the 'minimum standard' and a higher level of acceptability referred to as the
      'target'. The target can be shown to be a PPV of more than 5.1% for prevalent
      screens and more than 8.4% for incident screens. This paper will explore the role
      of PPV as a performance measure and show how making moderate increases in PPV for
      programmes with the lowest PPVs could lead to major improvements in the overall
      efficiency of the programme.

PMID- 16904892
TI  - The Footprint method to assess transmalleolar axis.
AB  - Torsional deformities of the lower extremities are a common reason for an
      orthopaedic consultation and are also part of the evaluation of a patient in gait
      analysis. This study assessed the level of agreement between, and the
      repeatability of, the Footprint method and two other methods (Prone and Jig) of
      measuring the transmalleolar axis (TMA) clinically. The Footprint method measures
      the TMA as the patient sits by projecting the position of the malleoli downwards
      onto lined paper while the lines of the paper are aligned with the knee axis. The
      Prone method projects the position of the malleoli upwards onto the sole of the
      foot and this is related to the visually estimated knee axis. The Jig method uses
      a tropometer to relate the angle between the tibial tubercle and the two
      malleoli. Two assessors measured twelve subjects using the three methods and six
      subjects were re-measured approximately 1 week later for repeatability. There was
      poor agreement between the three methods but the Footprint method was the most
      repeatable (coefficient of repeatability: 5.4). One observer then assessed the
      repeatability of the effect of simulated equinus on the Footprint method in 10
      normal subjects on 2 separate occasions 1 week apart. Equinus was obtained by
      having the subjects sit and firstly extend their knee and place the foot on the
      floor and secondly by placing the foot under consideration on a wedge. Both
      conditions introduced an offset into the measurement of the TMA when compared to
      the measurements with the ankle at neutral in the same subjects. The reliability
      of the Footprint method was then assessed using 10 inexperienced observers who
      measured nine normal subjects each on 2 separate occasions and their results
      compared with those from an experienced observer. The inexperienced observers
      were less repeatable than an experienced observer (coefficients of repeatability
      9.2 and 6.9, respectively). We recommend that different methods of measuring TMA
      should not be used interchangeably in clinical practice. The Footprint method was
      the most repeatable of the three methods tested and can be used for patients who
      have fixed equinus but the measurement was less repeatable when used by
      inexperienced observers.

PMID- 16904893
TI  - Lidocaine infiltration of the scalp does not completely abolish increased
      intraocular pressure due to skull pin insertion.
AB  - Insertion of skull pins results in haemodynamic perturbations, which can be
      blunted by local anaesthetic infiltration of the pin sites. No study has assessed
      the effects on intraocular pressure. General anaesthesia was induced in 71
      patients undergoing cervical spine surgery with attachment of Gardner Wells tongs
      to the skull. Skull pins were attached five minutes after induction following
      either saline (group I, 35 patients) or lidocaine (group II, 36 patients)
      infiltration of scalp. Intraocular pressure, mean arterial pressure and heart
      rate were recorded before (baseline), immediately after, and 60 s following pin
      insertion and analysed statistically. Insertion of pins increased intraocular
      pressure in both groups (from 8.4+/-2.7 to 14.2+/-3.0 mmHg in group I, and from
      8.8+/-2.3 to 12.7+/-2.7 mmHg in group II, P < 0.001), which persisted even at 60
      s but the increase was significantly greater in group I. Insertion of pins
      significantly increased blood pressure in group I only. We conclude that
      lidocaine infiltration at the skull pin sites for Gardner Wells tong attachment
      fails to completely abolish increased intraocular pressure.

PMID- 16904894
TI  - Therapeutic hypothermia for severely head-injured patients with acute subdural
      haematoma.
AB  - The benefit of hypothermia therapy for severely head-injured patients has been a
      matter of controversy, and the appropriate indications have yet to be clarified.
      The authors have employed mild hypothermia to treat severe acute subdural
      haematoma (ASDH) patients postoperatively as a means of controlling intracranial
      pressure. The potential roles of hypothermia in the treatment of severe ASDH
      patients are discussed. Between 1997 and 2000, 18 ASDH patients with a GCS on
      admission of 6 or less were treated by haematoma evacuation with postoperative
      mild hypothermia. The efficacy of hypothermia was evaluated retrospectively by
      comparing the outcome of these 18 patients with that of 15 ASDH patients who
      underwent surgery without postoperative hypothermia between 1993 and 1996.
      Hypothermia significantly increased both the survival and favorable outcome rates
      of the 18 ASDH patients, compared with the historic controls. However, the
      benefit of hypothermia was seen only in ASDH patients without associated cerebral
      contusion, and no significant protective effect of hypothermia was seen in ASDH
      patients with contusion. Hypothermia may be a useful postoperative therapeutic
      modality for severe ASDH without concomitant cerebral contusion. A future
      prospective study is warranted to support the conclusions of this retrospective
      study.

PMID- 16904895
TI  - Subdural haematomas complicating insertion of the low-pressure Novus
      hydrocephalus valve: a simple method for intra-operative testing of the anti
      siphon device.
AB  - We previously reported 52 patients with hydrocephalus who were followed up after
      insertion of low-pressure Novus valves. These valves have a normally open anti
      siphon device (ASD) incorporated. There were no cases of subdural haematomas
      (SDH). Subsequently, three new patients suffered SDH after insertion of these
      valves. We investigated a simple method for intra-operative testing of the ASD.
      These new patients had their valves replaced. In the laboratory, flow rates
      through five valves were recorded as a function of proximal positive pressure and
      distal negative pressures (siphoning). The flow rates were influenced by both
      proximal positive and distal negative pressures. The ASD stopped flow at distal
      negative pressures between -40 and -60 cm H(2)O. Proximal positive pressures
      increased this threshold. The flow can be measured by counting drops per minute.
      Three valves removed from patients were functioning as expected, one had
      unexpectedly slow flow at very high siphoning pressure and one had unexpectedly
      slow flow rates. In three patients with SDH complicating low-pressure Novus
      valves, the valves and anti-siphon devices were functioning adequately. Using a
      simple device, measuring flow rates in drops per minute was reliable and
      reproducible.

PMID- 16904896
TI  - Postoperative adjuvant treatment for pineal parenchymal tumour of intermediate
      differentiation.
AB  - Pineal parenchymal tumour of intermediate differentiation (PPTID) in adults is
      rare and a treatment strategy for this condition has not yet been established. We
      present a case of an elderly patient treated with postoperative adjuvant therapy
      using radio- and chemotherapy. This 60-year-old man presented with a 3-month
      history of memory disturbance, gait instability and double vision. Computed
      tomography and magnetic resonance imaging demonstrated a mass in the pineal
      region that suggested a malignant tumour. Partial removal of the tumour was
      undertaken via the right occipital transtentorial approach. The histological
      diagnosis was PPTID. Postoperative radio- and chemotherapy were administered,
      with a good response. Little is known about the clinical behaviour of PPTID in
      adults. Our treatment plan indicates one effective option for the management of
      such tumours.

PMID- 16904897
TI  - Comparison of craniotomy and craniectomy in patients with acute subdural
      haematoma.
AB  - Despite the increasing acceptance of craniectomy in patients with traumatic brain
      injury, the value of early decompressive craniectomy in patients with acute
      subdural haematoma is still under debate. In this retrospective study, we
      reviewed 180 patients with traumatic acute subdural haematoma, 111 of whom were
      treated with haematoma evacuation via craniotomy and 69 of whom were treated with
      early decompressive craniectomy. Due to the higher incidence of signs of
      herniation for patients in the craniectomy group, the mortality rate in this
      group was higher than that in the craniotomy group (53% vs. 32.3%). However,
      overall there was no significant difference in outcome between the two groups.
      Age and clinical signs of herniation were significantly associated with an
      unfavourable outcome, regardless of the type of surgery. Decompressive
      craniectomy did not seem to have a therapeutic advantage over craniotomy in
      traumatic acute subdural haematoma.

PMID- 16904899
TI  - REMOVED: Novel aminoquinonoid analogues of diospyrin: Synthesis, antitumour
      activity and preliminary QSAR studies.
AB  - This article has been retracted, consistent with Elsevier Policy on Article
      Withdrawal. Please see http://www.elsevier.com/locate/withdrawalpolicy. The
      Publisher apologizes for any inconvenience this may cause.

PMID- 16904898
TI  - Design, synthesis and evaluation of peptidomimetics based on substituted bicyclic
      2-pyridones-targeting virulence of uropathogenic E. coli.
AB  - Substituted bicyclic 2-pyridones, termed pilicides, are dipeptide mimetics that
      prevent pilus assembly in uropathogenic Escherichia coli. Here, we apply rational
      design to produce four classes of extended peptidomimetics based on two bioactive
      2-pyridones. The key intermediate in the synthesis was an amino-functionalised 2
      pyridone scaffold, which could be obtained via a mild and selective nitration and
      subsequent reduction. Procedures were then developed to further derivatize this
      amino-substituted core and a total of 24 extended peptidomimetics were
      synthesised and evaluated for chaperone affinity and in vivo antivirulence
      activity in P pili producing E. coli. Enhanced affinities for the target protein
      were observed within the generated set of compounds, while the ability to prevent
      pilus assembly in vivo was significantly decreased compared to the parent lead
      compounds. The results suggest that the limited in vivo potencies of the
      analogues are either uptake/distribution related or due to loss in binding
      specificity.

PMID- 16904900
TI  - Absorption microspectroscopy, theory and applications in the case of the
      photosynthetic compartment.
AB  - We performed microspectroscopic evaluation of the pigment composition of the
      photosynthetic compartments of both algae and higher plants. The feasibility of
      microspectroscopy for discriminating among species and/or phylogenetic groups was
      tested on laboratory cultures. Gaussian bands decompositions, and a fitting
      algorithm, together with fourth-derivative transformation of absorbance spectra,
      provided a reliable discrimination among chlorophylls, phycobiliproteins and
      carotenoids. Comparative analysis of absorption spectra highlighted the
      evolutionary grouping of the algae into three main lineages in accordance with
      the most recent endosymbiotic theories.

PMID- 16904901
TI  - Decontamination of gum arabic with gamma-rays or electron beams and effects of
      these treatments on the material.
AB  - Samples of gum arabic were irradiated to 2.5, 5.0 and 10.0 kGy with gamma-rays
      and electrons for a comparison of the relative effectiveness of these two
      treatments and for investigation of the effects of these doses of radiation on
      the material. The initial raw samples were contaminated with various strains of
      bacteria, including fungi and spore-forming bacteria (such as Enteroccus
      faecalis, Bacillus cereus and Closstridum perfringens). The samples were
      completely decontaminated by irradiation to 10.0 kGy with either gamma-rays or
      electrons. Slight changes in the physical properties of the material, such as
      darkening and viscosity decrease, were noticeable after irradiation to the
      highest dose, but not to the lower doses. A linear relationship between the
      absorbed dose and the material degradation was observed. gamma-rays were found to
      be more destructive than electrons. An optimal decontamination regimen for the
      material to be used in food industry and medicine would be irradiation to 5 kGy
      with electrons. It would be a safe alternative to the methods using hazardous
      chemicals, such as pesticides and fungicides. It would provide sufficient
      decontamination without adverse effects on the physical properties of the final
      products.

PMID- 16904902
TI  - The abbreviated comprehensive geriatric assessment (aCGA) for use in the older
      cancer patient as a prescreen: scoring and interpretation.
AB  - The abbreviated CGA (aCGA) can be used as a prescreening assessment to identify
      patients who would most benefit from the complete CGA. OBJECTIVE: To develop
      cutpoints for scoring the aCGA that are consistent with existing limitations as
      revealed by the full CGA. DESIGN/SETTING: A retrospective chart review of
      patients at the H. Lee Moffitt Cancer Center. PARTICIPANTS: Over 500 charts
      between 1995 and 2001 were reviewed on cancer patients 70 and over. MEASUREMENTS:
      Each of the four domains: functional status (activities of daily living (ADL),
      instrumental activities of daily living (IADL), depression, using the geriatric
      depression scale (GDS), and cognition using the mini-mental state examination
      (MMSE)) are scored separately. RESULTS: For the depression domain, a score of 2
      or more toward depression indicates that the entire GDS be administered. For the
      MMSE, a score of 6 or lower indicates necessity of the entire MMSE. For the
      ADL/IADL, any deficit on either scale (needs assistance or complete assistance)
      requires further clinical evaluation using the entire instruments. CONCLUSIONS:
      These guidelines provide the clinician with parameters to target patients most
      likely to benefit from more intensive geriatric evaluation.

PMID- 16904903
TI  - The c-Myc target gene network.
AB  - For more than a decade, numerous studies have suggested that the c-Myc oncogenic
      protein is likely to broadly influence the composition of the transcriptome.
      However, the evidence required to support this notion was made available only
      recently, much to the anticipation of an eagerly awaiting field. In the past 5
      years, many high-throughput screens based on microarray gene expression
      profiling, serial analysis of gene expression (SAGE), chromatin
      immunoprecipitation (ChIP) followed by genomic array analysis, and Myc-methylase
      chimeric proteins have generated a wealth of information regarding Myc responsive
      and target genes. From these studies, the c-Myc target gene network is estimated
      to comprise about 15% of all genes from flies to humans. Both genomic and
      functional analyses of c-Myc targets suggest that while c-Myc behaves as a global
      regulator of transcription, groups of genes involved in cell cycle regulation,
      metabolism, ribosome biogenesis, protein synthesis, and mitochondrial function
      are over-represented in the c-Myc target gene network. c-Myc also consistently
      represses genes involved in cell growth arrest and cell adhesion. The
      overexpression of c-Myc predisposes cells to apoptosis under nutrient or growth
      factor deprivation conditions, although the critical sets of genes involved
      remain elusive. Despite tremendous advances, the downstream target genes that
      distinguish between physiologic and tumorigenic functions of c-Myc remain to be
      delineated.

PMID- 16904904
TI  - A semi-automated large-scale process for the production of recombinant tagged
      proteins in the Baculovirus expression system.
AB  - The efficient preparation of recombinant proteins at the lab-scale level is
      essential for drug discovery, in particular for structural biology, protein
      interaction studies and drug screening. The Baculovirus insect-cell expression
      system is one of the most widely applied and highly successful systems for
      production of recombinant functional proteins. However, the use of eukaryotic
      cells as host organisms and the multi-step protocol required for the generation
      of sufficient virus and protein has limited its adaptation to industrialized high
      throughput operation. We have developed an integrated large-scale process for
      continuous and partially automated protein production in the Baculovirus system.
      The instrumental platform includes parallel insect-cell fermentation in 10L
      BioWave reactors, cell harvesting and lysis by tangential flow filtration (TFF)
      using two custom-made filtration units and automated purification by multi
      dimensional chromatography. The use of disposable materials (bags, filters and
      tubing), automated cleaning cycles and column regeneration, prevent any cross
      contamination between runs. The preparation of the clear cell lysate by
      sequential TFF takes less than 2 h and represents considerable time saving
      compared to standard cell harvesting and lysis by sonication and ultra
      centrifugation. The process has been validated with 41 His-tagged proteins with
      molecular weights ranging from 20 to 160 kDa. These proteins represented several
      families, and included 23 members of the deubiquitinating enzyme (DUB) family.
      Each down-stream unit can process four proteins in less than 24 h with final
      yields between 1 and 100 mg, and purities between 50 and 95%.

PMID- 16904905
TI  - Expression, purification, and characterization of Pseudomonas aeruginosa SecA.
AB  - A secA gene from Pseudomonas aeruginosa PAO1 was amplified and expressed in
      Escherichia coli BL21.19 (secA13) under conditions where E. coli SecA was
      depleted. The binding of P. aeruginosa SecA (PaSecA) to the SP-Sepharose column
      was facilitated by ammonium sulfate fractionation but was not necessary for E.
      coli SecA (EcSecA) as the later bound more efficiently. PaSecA and EcSecA were
      purified by the single chromatographic step to greater than 98% purity and had a
      recovery of more than 20 and 40%, respectively, from the soluble fraction. This
      simple step purification obtained a higher homogeneity than previously reported.
      Cross-reactivity by immunoblotting showed that the purified PaSecA contained
      little EcSecA if any. The purified PaSecA is a dimer in solution, as judged by
      size exclusion chromatography, and is slightly larger than its counterpart EcSecA
      with an estimated molecular weight of 240 kDa. Further studies by the
      sedimentation velocity method indicate that PaSecA tends to remain as a monomer
      in solution. The purified PaSecA possessed ATPase activity; the intrinsic and
      liposome-stimulated ATPase specific activities of PaSecA were approximately 50%
      of EcSecA.

PMID- 16904906
TI  - Strategies to maximize heterologous protein expression in Escherichia coli with
      minimal cost.
AB  - Automation and miniaturization are key issues of high-throughput research
      projects in the post-genomic era. The implementation of robotics and
      parallelization has enabled researchers to process large numbers of protein
      targets for structural studies in a short time with reasonable cost efficiency.
      However, the cost of implementing the robotics and parallelization often prohibit
      their use in the traditional academic laboratory. Fortunately, multiple groups
      have made significant efforts to minimize the cost of heterologous protein
      expression for the production of protein samples in quantities suitable for high
      resolution structural studies. In this review, we describe recent efforts to
      continue to minimize the cost for the parallel processing of multiple protein
      targets and focus on those materials and strategies that are highly suitable for
      the traditional academic laboratory.

PMID- 16904907
TI  - Crystal structure of the temperature-sensitive and allosteric-defective
      chaperonin GroELE461K.
AB  - The chaperonin GroEL adopts a double-ring structure with various modes of
      allosteric communication. The simultaneous positive intra-ring and negative inter
      ring co-operativities alternate the functionality of the folding cavities in both
      protein rings. Negative inter-ring co-operativity is maintained through different
      inter-ring interactions, including a salt bridge involving Glu 461. Replacement
      of this residue by Lys modifies the temperature sensitivity of the substrate
      folding activity of this protein, most likely as a result of the loss of inter
      ring co-operativity. The crystal structure of the mutant chaperonin GroELE461K
      has been determined at 3.3A and compared with other structures: the wild-type
      GroEL, an allosteric defective GroEL double mutant and the GroEL-GroES-(ADP)7
      complex. The inter-ring region of the mutant exhibits the following
      characteristics: (i) no salt-bridge stabilizes the inter-ring interface; (ii) the
      mutated residue plays a central role in defining the relative ring rotation (of
      about 22 degrees) around the 7-fold axis; (iii) an increase in the inter-ring
      distance and solvent accessibility of the inter-ring interface; and (iv) a 2-fold
      reduction in the stabilization energy of the inter-ring interface, due to the
      modification of inter-ring interactions. These characteristics explain how the
      thermal sensitivity of the protein's fundamental properties permits GroEL to
      distinguish physiological (37 degrees C) from stress (42 degrees C) temperatures.

PMID- 16904908
TI  - Cdc48 is required for the stability of Cut1/separase in mitotic anaphase.
AB  - Separase, a large protease essential for sister chromatid separation, cleaves the
      cohesin subunit Scc1/Rad21 during anaphase and leads to dissociation of the link
      between sister chromatids. Securin, a chaperone and inhibitor of separase, is
      ubiquitinated by APC/cyclosome, and degraded by 26S proteasome in anaphase.
      Cdc48/VCP/p97, an AAA ATPase, is involved in a variety of cellular activities,
      many of which are implicated in the proteasome-mediated degradation. We
      previously reported that temperature-sensitive (ts) fission yeast
      Schizosaccharomyces pombe cdc48 mutants were suppressed by multicopy plasmid
      carrying the cut1(+)/separase gene and that the defective mitotic phenotypes of
      cut1 and cdc48 were similar. We here describe characterizations of Cdc48 mutant
      protein and the role of Cdc48 in sister chromatid separation. Mutant residue
      resides in the conserved D1 domain within the central hole of hexamer, while
      Cdc48 mutant protein possesses the ATPase activity. Consistent with the
      phenotypic similarity and the rescue of cdc48 mutant by overproduced
      Cut1/separase, the levels of Cut1 and also Cut2 are diminished in cdc48 mutant.
      We show that the stability of Cut1 during anaphase requires Cdc48. Cells lose
      viability during the traverse of anaphase in cdc48 mutant cells. Cdc48 may
      protect Cut1/separase and Cut2/securin against the instability during
      polyubiquitination and degradation in the metaphase-anaphase transition.

PMID- 16904909
TI  - Age-related differences in muscle activity, stride frequency and heart rate
      response during walking in water.
AB  - This study aimed to examine whether walking in water produces age-related
      differences in muscle activity, stride frequency (SF), and heart rate (HR)
      response. Surface electromyography (EMG) was used to evaluate muscle activities
      in six older and six young subjects while they walked in water immersed to the
      level of the xiphoid process. The trials in water utilized the Flowmill which
      consists of a treadmill at the base of a water flume. The measurement of maximal
      voluntary contraction (MVC) of each muscle was made prior to the gait analysis.
      The %MVCs, which refer to the surface EMG measures, from the gastrocnemius of the
      older subjects were significantly lower than those of the young subjects, in
      every experimental condition (P<0.05). In contrast, the %MVCs from the rectus
      femoris (P<0.05) and the biceps femoris (P<0.001) of older subjects were
      significantly greater than those of young subjects in every experimental
      condition. Moreover, the SFs of older subjects were also significantly greater
      than those of young subjects (P<0.05), while the HR responses of older and young
      subjects were similar. In conclusion, the older subjects had increased hip
      musculature activity and decreased ankle plantar flexor activity while walking in
      water, compared with the young subjects.

PMID- 16904910
TI  - Interfering effects of multitasking on muscle activity in the upper extremity.
AB  - Multitasking, where workers are required to perform multiple physical tasks with
      various levels of cognitive load is common in today's workplace. Simultaneous
      physical and mental demands are thought to cause task interference and likely
      increase muscle activity. To test the interfering effects of multitasking, 16
      healthy participants performed hand and shoulder exertions with combinations of
      four grip conditions (no grip, 30% grip with low precision, 30% grip with high
      precision, and maximal grip) and three shoulder conditions at 90 degrees
      abduction (maintaining posture, 40% force-controlled moment, 40% posture
      controlled moment), with and without the Stroop test while surface EMG was
      recorded from eight upper extremity muscles. Both 40% MVC shoulder moments
      increased extrinsic forearm muscle activity by 2-4% MVE (p<0.01). Grip exertion
      at 30% MVC reduced anterior and middle deltoid activity by 2% MVE (p<0.01).
      Exerting a constant force against the transducer (force-controlled) required 3-4%
      MVE greater middle and posterior deltoid activity (p<0.001) compared to
      supporting an equivalent inertial load at the same shoulder angle (posture
      controlled). Performing the mental task (Stroop test) concurrently with either
      40% MVC shoulder moments significantly increased trapezius activity by nearly 2%
      MVE (p<0.05). Interestingly, the Stroop test also reduced all deltoid activity by
      1% MVE (p<0.05). The addition of both the Stroop test and force-control shoulder
      exertion independently reduced maximal grip force by 7% and 10% MVC,
      respectively. These results suggest that more complex workplace tasks may act to
      increase muscle load or interfere with task performance. These small but
      significant findings may play a role in the development of long-term
      musculoskeletal disorders in the workplace.

PMID- 16904911
TI  - A spatially unbiased atlas template of the human cerebellum.
AB  - This article presents a new high-resolution atlas template of the human,
      cerebellum and brainstem, based on the anatomy of 20 young healthy individuals.
      The atlas is spatially unbiased, i.e., the location of each structure is equal to
      the expected location of that structure across individuals in MNI space, a result
      that is cross-validated with an independent sample of 16 individuals. At the same
      time, the new template preserves the anatomical detail of cerebellar structures
      through a nonlinear atlas generation algorithm. In comparison to current whole
      brain templates, it allows for an improved voxel-by-voxel normalization for
      functional MRI and lesion analysis. Alignment to the template requires that the
      cerebellum and brainstem are isolated from the surrounding tissue, a process for
      which an automated algorithm has been developed. Compared to normalization to the
      MNI whole-brain template, the new method strongly improves the alignment of
      individual fissures, reducing their spatial spread by 60%, and improves the
      overlap of the deep cerebellar nuclei. Applied to functional MRI data, the new
      normalization technique leads to a 5-15% increase in peak t values and in the
      activated volume in the cerebellar cortex for movement vs. rest contrasts. This
      indicates that the new template significantly improves the overlap of
      functionally equivalent cerebellar regions across individuals. The template and
      software are freely available as an SPM-toolbox, which also allows users to
      relate the new template to the annotated volumetric (Schmahmann, J.D., Doyon, J.,
      Toga, A., Petrides, M., Evans, A. (2000). MRI atlas of the human cerebellum. San
      Diego: Academic Press) and surface-based (Van Essen, D.C. (2002a) Surface-based
      atlases of cerebellar cortex in the human, macaque, and mouse. Ann. N. Y. Acad.
      Sci. 978:468-479.) atlas of one individual, the "colin27"-brain.

PMID- 16904912
TI  - Four subgroups of Alzheimer's disease based on patterns of atrophy using VBM and
      a unique pattern for early onset disease.
AB  - To clarify the involvement of the posterior cingulate cortex (PCC) in Alzheimer's
      disease (AD), we analyzed brain volume loss by voxel-based morphometry. Forty
      patients with non-familial AD and 20 patients with mild cognitive impairment
      (MCI) were recruited and compared to 88 elderly volunteers and 40 young
      volunteers. Local atrophy with aging was observed bilaterally in the perisylvian
      opercula, anterior cingulate cortex, caudate head, dorsomedial thalamus and
      parahippocampal cortex. In addition to those, atrophy in AD patients was observed
      in the amygdala, hippocampus, subcallosal region, posterior-associated cortices
      and PCC. We classified AD into four subgroups according to the atrophy pattern;
      atrophy in the amygdala/hippocampal formations (Hipp), in the Hipp and posterior
      cortices, in the Hipp and PCC and in the PCC and posterior cortices (PCC/-TOPa).
      As a result, the probability of PCC/-TOPa was 90% for ages <65 years, whereas
      that of the Hipp was 100% for disease duration >36 months. PCC atrophy was found
      in 16 of 40 AD patients and eight of 20 MCI patients. There seemed to be two
      subgroups with atrophy of the PCC, the one with disease progression and the other
      without. The latter had characteristic features of early onset and no significant
      atrophy in the amygdala/anterior hippocampus. There are at least four atrophy
      patterns that raise doubts about a single disease entity or progression in AD.
      This may reflect a different hierarchical pattern of progression in patients who
      have atrophy in PCC and posterior cortices when compared to the Braak staging
      scheme.

PMID- 16904914
TI  - Phylogenetic utility of rapidly evolving DNA at high taxonomical levels:
      contrasting matK, trnT-F, and rbcL in basal angiosperms.
AB  - The prevailing view in molecular systematics is that relationships among
      distantly related taxa should be inferred using DNA segments with low rates of
      evolution. However, recent analyses of sequences from the rapidly evolving matK
      and trnT-trnF regions yielded well resolved and highly supported trees for early
      diverging angiosperms. We compare here the phylogenetic structure in matK, trnT
      F, and rbcL datasets for the same 42, primarily basal angiosperm taxa.
      Phylogenetic trees based on matK or trnT-F are far more robust than those based
      on rbcL. Combined analysis of the rapidly evolving regions provides support for
      higher-level relationships stronger than that derived from analyses of multi-gene
      datasets of up to several fold the number of characters analyzed here. In
      addition to displaying a higher percentage of parsimony-informative characters,
      the average phylogenetic signal per informative character is significantly higher
      in the datasets from rapidly evolving DNA than in the more slowly evolving rbcL,
      as detected using resampling of identical numbers of parsimony-informative
      characters from the data matrices and subjecting different statistics for overall
      tree robustness and phylogenetic signal to significance tests. Automated via a
      set of scripts, the method used here should be easily extendable to comparisons
      of a broader range of genomic regions for varying taxon samplings. The relative
      performance of markers correlates not only with a lower mean homoplasy in matK
      and trnT-trnF compared to rbcL, but in particular correlates negatively with the
      percentage of sites exhibiting maximum or close to maximum homoplasy. A
      likelihood ratio test confirms that the rapidly evolving gene matK evolves
      significantly closer to neutrality, which may be one of the underlying factors
      for lower levels of overall homoplasy. Our results are in line with evidence from
      simulation studies suggesting that the deleterious effect of multiple hits in
      using rapidly evolving DNA at rather deep phylogenetic levels may have been
      overestimated, and thus promote extending the use of rapidly evolving DNA to
      deeper phylogenetic levels.

PMID- 16904913
TI  - The assessment of hemispheric lateralization in functional MRI--robustness and
      reproducibility.
AB  - Various methods have been proposed to calculate a lateralization index (LI) on
      the basis of functional magnetic resonance imaging (fMRI) data. Most of them are
      either based on the extent of the activated brain region (i.e., the number of
      "active" voxels) or the magnitude of the fMRI signal change. The purpose of the
      present study was to investigate the characteristics of various variants of these
      approaches and to identify the one that yields the most robust and reproducible
      results. Robustness was assessed by evaluating the dependence on arbitrary
      external parameters, reproducibility was assessed by Pearson's correlation
      coefficient. LIs based on active voxels counts at one single fixed statistical
      threshold as well as LIs based on unthresholded signal intensity changes (i.e.,
      based on all voxels in a region of interest) yielded neither robust nor
      reproducible laterality results. Instead, the lateralization of a cognitive
      function was best described by "thresholded" signal intensity changes where the
      activity measure was based on signal intensity changes in those voxels in a
      region of interest that exceeded a predefined activation level. However, not all
      other approaches should be discarded completely since they have their own
      specific application fields. First, LIs based on active voxel counts in the form
      of p-value-dependent lateralization plots (LI=LI(p)) can be used as a
      straightforward measure to describe hemispheric dominance. Second, LIs based on
      active voxel counts at variable thresholds (standardized by the total number of
      active voxels) are a good alternative for big regions of interest since LIs based
      on signal intensity changes are restricted to small ROIs.

PMID- 16904915
TI  - Molecular phylogenetic analysis of Commiphora (Burseraceae) yields insight on the
      evolution and historical biogeography of an "impossible" genus.
AB  - Expansion of the arid zone of sub-Saharan tropical Africa during the Miocene is
      posited as a significant contributing factor in the evolution of contemporary
      African flora. Nevertheless, few molecular phylogenetic studies have tested this
      hypothesis using reconstructed historical biogeographies of plants within this
      zone. Here, we present a molecular phylogeny of Commiphora, a predominantly
      tropical African, arid-adapted tree genus, in order to test the monophyly of its
      taxonomic sections and identify clades that will help direct future study of this
      species-rich and geographically widespread taxon. We then use multiple fossil
      calibrations of Commiphora phylogeny to determine the timing of well-supported
      diversification events within the genus and interpret these age estimates to
      determine the relative contribution of vicariance and dispersal in the expansion
      of Commiphora's geographic range. We find that Commiphora is sister to Vietnamese
      Bursera tonkinensis and that its crown group radiation corresponds with the onset
      of the Miocene.

PMID- 16904916
TI  - Molecular phylogeny of the Branchiopoda (Crustacea)--multiple approaches suggest
      a 'diplostracan' ancestry of the Notostraca.
AB  - The evolutionary history of Branchiopoda (Crustacea) traditionally has attracted
      considerable interest due to the diversity of the group. Recently molecular
      methods have been applied to the study of branchiopod systematics with some
      success, but central questions, such as the phylogenetic position of Laevicaudata
      and Notostraca, and the intrinsic cladoceran phylogeny, remain unanswered. We
      examined the phylogeny of Branchiopoda by using two genes, mitochondrial 16S rRNA
      and nuclear 28S rRNA, which previously have seen little use for inferring
      branchiopod phylogeny. The number of ingroup taxa included was 42, representing
      all eight extant branchiopod orders. The data were analyzed using parsimony,
      maximum likelihood, and Bayesian Inference of phylogeny. Some higher-level taxa
      were supported in all analyses of the combined data: Phyllopoda, Cladoceromorpha,
      Cladocera, and Gymnomera. Other higher-level taxa were not supported in any
      trees: Diplostraca and Conchostraca. A case is made for a possible diplostracan
      ingroup position of Notostraca based on our data and on previously published
      molecular and morphological evidence. The recent discovery of a Devonian
      branchiopod, which is morphologically an intermediate between a notostracan and a
      'conchostracan', is congruent with a diplostracan ancestry of Notostraca.

PMID- 16904917
TI  - Speciation dynamics in the Australo-Papuan Meliphaga honeyeaters.
AB  - The Australo-Papuan Meliphaga honeyeaters have diversified over a wide range of
      habitats and elevational zones and are one of the few regionally known cryptic
      avian radiations. Using a combined 1580 bp of mitochondrial and nuclear DNA we
      investigate the species limits, systematic affinities and biogeographic history
      of Meliphaga. We also investigate the role of spatial sorting mechanisms,
      including altitudinal replacement and niche partitioning, as mechanisms
      underlying the adaptive radiation of this group. Phylogenetic analysis indicates
      that the genus Meliphaga comprises at least 16 species, three more than
      recognized in current classifications. The genus divides into two clades; the
      species-poor lewinii group, and the larger analoga group that has diversified
      into a wider range of vertical, vegetational and elevational niches. The basal
      division of each clade into an Australian and New Guinean assemblage was likely
      induced by the formation of the Arafura Sea during the early Pliocene (
      approximately 4 MYA) with a single reinvasion of Australia by the open forest
      species M. gracilis during the early Pleistocene (1.2-1.5 MYA) via intermittent
      land bridges or island hopping. Most recent sister species were found to replace
      each other geographically within the same ecological and elevational zone
      conforming to the classical allopatric mode of speciation. In contrast, M.
      orientalis (650-1950 m) and M. analoga (0-1100 m) were found to replace each
      other altitudinally across ecological zones providing empirical support for
      altitudinal speciation as a mechanism of diversification in a montane avifauna.
      We find no evidence of sympatric speciation (co-existing sister lineages) and
      suggest that spatial segregation within the habitat (niche partitioning) is
      primarily a mechanism enabling more divergent species to coexist.

PMID- 16904918
TI  - Apoptotic cell death increases with senescence in normal human dermal fibroblast
      cultures.
AB  - Normal human dermal fibroblasts have a limited life-span in vitro and stop
      proliferation after a fixed number of cell divisions. This process by which cells
      stop proliferation is called senescence. Senescence is also characterized by a
      decrease in the total cell number. In this study, we characterized an increase in
      cell death in normal human dermal fibroblasts in vitro as a function of
      increasing cell passage. With increasing passage, human fibroblasts showed an
      increase in the number of dead cells and increased DNA fragmentation as
      determined by flow cytometry. Serial passage of human fibroblasts also resulted
      in mitochondrial dysfunction, represented by a loss of mitochondrial membrane
      potential. The apoptotic markers caspase-3 and cytochrome c were both found to
      increase in senescent cells. These results suggest the activation of an apoptotic
      pathway within a population of human fibroblasts as a function of cell passage.

PMID- 16904919
TI  - Pharmacological dissociation of trace and long-delay fear conditioning in young
      rats.
AB  - In most studies comparing trace and delay conditioning, CS duration is kept
      constant across training conditions but the interstimulus interval (ISI), the
      time from CS onset to US onset, is confounded. In the infrequently used long
      delay condition, however, ISI is kept constant across the trace and delay
      conditions but CS duration varies. A recent study reported that trace and long
      delay fear conditioning have the same developmental trajectory, with both
      emerging later in development than standard-delay conditioning (). Past studies
      have shown that trace conditioning is mediated by the cholinergic system; given
      the parallel developmental emergence of trace and long-delay conditioning, the
      present study examined whether the cholinergic system also mediates long-delay
      conditioning. Two experiments, both involving Sprague-Dawley-derived rats and
      using freezing as a measure of learned fear, showed that the cholinergic system
      is critically involved in trace conditioning but is not involved in long-delay
      conditioning. Specifically, pre-training injections of the muscarinic receptor
      antagonist scopolamine impaired acquisition of a CS-US association in 32-day-old
      rats trained with a trace procedure but had no effect on rats this age trained
      with a long-delay procedure (Experiment 1). Similarly, pre-training injections of
      physostigmine, a cholinesterase inhibitor, enhanced acquisition of trace
      conditioning in 25-day-old rats but had no effect on long-delay conditioning in
      rats this age (Experiment 2). Taken together, the results indicate that despite
      the similarities between trace and long-delay conditioning in terms of
      developmental emergence and level of conditioned responding, they are mediated by
      different physiological systems.

PMID- 16904920
TI  - Androgens' effects to enhance learning may be mediated in part through actions at
      estrogen receptor-beta in the hippocampus.
AB  - Testosterone (T) may enhance cognitive performance. However, its mechanisms are
      not well understood. First, we hypothesized that if T's effects are mediated in
      part through actions of its 5alpha-reduced metabolites, dihydrotestosterone (DHT)
      and/or 3alpha-androstanediol (3alpha-diol) in the hippocampus, then T, DHT, and
      3alpha-diol-administration directly to the hippocampus should enhance learning
      and memory in the inhibitory avoidance task. In order to test this hypothesis,
      gonadectomized (GDX) male rats were administered T, DHT, or 3alpha-diol via
      intrahippocampal inserts immediately following training in the inhibitory
      avoidance task. We found that T tended to increase, and DHT and 3alpha-diol
      significantly increased, performance in the inhibitory avoidance task compared to
      vehicle-administered GDX rats. Second, we hypothesized that, if androgens'
      effects are due in part to actions of 3alpha-diol in the hippocampus, then
      systemic or intrahippocampal administration of 3alpha-diol should significantly
      enhance cognitive performance of GDX male rats. Third, we hypothesized that, if
      androgen metabolites can have actions at estrogen receptors (ERs) in the
      hippocampus, then administration of ER antisense oligonucleotides (AS-ODNs)
      directly to the hippocampus of GDX, 3alpha-diol replaced, rats would decrease
      learning in the inhibitory avoidance task. We found that intrahippocampal
      administration of AS-ODNs for ERbeta, but not ERalpha, significantly decreased
      learning and memory of 3alpha-diol replaced rats. Together, these findings
      suggest that T's effects to enhance learning and memory may take place, in part,
      through actions of its metabolite, 3alpha-diol, at ERbeta in the dorsal
      hippocampus.

PMID- 16904921
TI  - The links between membrane composition, metabolic rate and lifespan.
AB  - The acyl composition of tissue phospholipids varies in a systematic manner among
      species. Phospholipids, and thus membrane bilayers, from the tissues of small
      mammal and bird species have a high content of docosahexaenoic acid (DHA)
      compared to large species. A similar difference exists between the tissues of
      endothermic mammals and ectothermic reptiles. High DHA content in phospholipids
      is associated with high metabolic activity and this observation has led to the
      development of the "membrane pacemaker" theory of metabolism. This proposes that
      highly polyunsaturated acyl chains impart physical properties to membrane
      bilayers that enhance and speed up the molecular activity of membrane proteins
      and consequently the metabolic activity of cells, tissues and the whole animal.
      The brain has highly polyunsaturated membranes irrespective of body size and
      possible reasons for this are discussed. Highly polyunsaturated acyl chains are
      very susceptible to peroxidative damage. It is suggested that these chemical
      properties of highly polyunsaturated membrane acyl chains have important
      implications for understanding aging and the determination of longevity.

PMID- 16904922
TI  - Glucose metabolism during embryogenesis of the hard tick Boophilus microplus.
AB  - Glucose metabolism plays an essential role in the physiology and development of
      almost all living organisms. In the present study we investigated glucose
      metabolism during the embryogenesis of the hard tick Boophilus microplus. An
      increase in glucose and glycogen content during the embryonic development of B.
      microplus was detected and shown to be due to the high enzyme activity of both
      gluconeogenesis and glycolytic pathways. Glucose 6-phosphate (G-6P), formed by
      hexokinase, is driven mainly to pentose-phosphate pathway, producing fundamental
      substrates for cellular biosynthesis. We detected an increase in glucose 6
      phosphate dehydrogenase and pyruvate kinase activities after embryo
      cellularization. Accumulation of key metabolites such as glycogen and glucose was
      monitored and revealed that glycogen content decreases from day 1 up to day 6, as
      the early events of embryogenesis take place, and increases after the formation
      of embryo cellular blastoderm on day 6. Glucose and guanine (a sub-product of
      amino acids degradation in arachnids) accumulate almost concomitantly. The
      activity of phosphoenolpyruvate carboxykinase was increased after embryo
      cellularization. Taken together these data indicate that glycogen and glucose,
      formed during B. microplus embryogenesis after blastoderm formation, are produced
      by intense gluconeogenesis.

PMID- 16904923
TI  - Local changes in the insulin-like growth factor system in human skeletal muscle
      assessed by microdialysis and arterio-venous differences technique.
AB  - IGF-I plays a direct role in whole body glucose homeostasis primarily by
      stimulating skeletal muscle glucose uptake. IGF-I is also involved in exercise
      induced muscle hypertrophy. Knowledge regarding local changes in muscle IGF-I
      bioavailability and its regulation by IGFBPs at rest and during exercise is
      limited. We have therefore explored changes in total IGF-I levels as well as
      circulating IGFBP levels and their post-translational modifications over an
      exercising leg. For the first time we have determined IGF-I levels in exercising
      skeletal muscle microdialysate in an attempt to assess local IGF-I
      bioavailability. Eighteen healthy young men performed one legged knee-extension
      exercise during 45min. Blood samples were taken from the femoral artery and vein
      of the exercising leg. No significant differences between arterial and venous
      concentrations of total IGF-I or IGFBP-1 were detected over the leg at any time.
      IGF-I concentrations increased significantly during exercise in the artery but
      not in the vein. Total IGFBP-1 increased after exercise in both artery and vein.
      The increase in non-plus less phosphorylated forms of IGFBP-1 was less pronounced
      and did not reach statistical significance. The proportion of fragmented IGFBP-3
      (IGFBP-3 proteolysis) assessed by Western immunoblotting did not change
      significantly during or after exercise. Although optimization and validation of
      IGF-I determinations in muscle microdialysate (md) will be required, our first
      results using this technique demonstrate a significant 2-fold increase in mdIGF-I
      collected during and after exercise. We conclude that determination of A-V
      differences appears to be of limited value in the assessments of local muscle
      change in the IGF-system. A substantial release of IGF-I during short time is
      required to detect significant change in the large circulating store of IGF-I. We
      suggest that an optimized and validated microdialysis technique for determination
      of local IGF-I may be advantageous in future studies.

PMID- 16904924
TI  - Molecular analysis in two beta-mannosidosis patients: description of a new adult
      case.
AB  - beta-Mannosidosis is a lysosomal storage disorder caused by deficiency of beta
      mannosidase. Thirteen families with cases of beta-mannosidosis have been
      described including one case previously reported by our group. We present
      clinical and biochemical data in a new adult case, and the molecular analyses in
      both this new case and the one previously reported. We detected four novel
      mutations: p.R182W, p.G392E, p.W466X and c.1848delA. Discrepancies between
      genomic DNA and cDNA results when detecting this last deletion suggested a
      nonsense-mediated decay cell process (NMD).

PMID- 16904925
TI  - Lactobacillus casei administration reduces lung injuries in a Streptococcus
      pneumoniae infection in mice.
AB  - The effect of the oral administration of Lactobacillus casei on the prevention of
      a Streptococcus pneumoniae lung infection in a mouse experimental model was
      studied, analyzing the innate and specific immune response. Adult Swiss albino
      mice were treated with L. casei (10(9)CFU/day) for 2, 5 and 7 d. Mice were
      infected intranasally with S. pneumoniae (10(6)CFU/mouse) after each treatment
      and the microbiological, histopathological and host responses were determined for
      15 d after infection. Feeding L. casei for 2 d induced a faster clearance of S.
      pneumoniae, with a lower number of pneumococci in lung and a shorter period of
      septicemia than in the control group. L. casei administration induced activation
      of phagocytes as evidenced by the strong myeloperoxidase activity and the nitro
      blue tetrazolium assay in lung. Mice given L. casei for 2 d showed higher levels
      of anti-pneumococcal serum IgG and bronchoalveolar lavage IgA than the control
      mice. The group fed L. casei for 2 d could beneficially regulate the balance
      between tumor necrosis factor alpha and interleukin 10, allowing a more effective
      immune response against infection and modulating the inflammatory response, with
      less damage to the lung.

PMID- 16904926
TI  - The INTERMED questionnaire for predicting return to work after a
      multidisciplinary rehabilitation program for chronic low back pain.
AB  - OBJECTIVES: To evaluate the performance of the INTERMED questionnaire score,
      alone or combined with other criteria, in predicting return to work after a
      multidisciplinary rehabilitation program in patients with non-specific chronic
      low back pain. METHODS: The INTERMED questionnaire is a biopsychosocial
      assessment and clinical classification tool that separates heterogeneous
      populations into subgroups according to case complexity. We studied 88 patients
      with chronic low back pain who followed an intensive multidisciplinary
      rehabilitation program on an outpatient basis. Before the program, we recorded
      the INTERMED score, radiological abnormalities, subjective pain severity, and
      sick leave duration. Associations between these variables and return to full-time
      work within 3 months after the end of the program were evaluated using one-sided
      Fisher tests and univariate logistic regression followed by multivariate logistic
      regression. RESULTS: The univariate analysis showed a significant association
      between the INTERMED score and return to work (P<0.001; odds ratio, 0.90; 95%
      confidence interval, 0.86-0.96). In the multivariate analysis, prediction was
      best when the INTERMED score and sick leave duration were used in combination
      (P=0.03; odds ratio, 0.48; 95% confidence interval, 0.25-0.93). CONCLUSION: The
      INTERMED questionnaire is useful for evaluating patients with chronic low back
      pain. It could be used to improve the selection of patients for intensive
      multidisciplinary programs, thereby improving the quality of care, while reducing
      healthcare costs.

PMID- 16904927
TI  - Bilateral tibial stress fracture presenting as painful edemas in lower limbs.
AB  - Bilateral stress fracture of the tibia is infrequent. This paper presents an
      unusual case of a 73-year-old man who sustained a bilateral stress fracture of
      the tibia presenting as painful edemas in lower limbs. The radiographic and
      scintigraphic examination confirmed the diagnosis of the fractures. In addition,
      the patient was receiving androgen deprivation therapy with GnRH analogs for the
      treatment of prostate cancer and the bone density measurements confirmed the
      presence of osteoporosis. Treatment with restricted weight bearing was associated
      with improvement of clinical symptoms. Early recognition and diagnosis of this
      injury is essential for treating the underlying osteoporosis as well as the
      fracture.

PMID- 16904928
TI  - Late onset Behcet's disease.
AB  - Behcet's disease is characterized by recurrent mouth ulcerations associated with
      two of the following clinical manifestations: recurrent genital ulcerations,
      ophthalmic and cutaneous lesions and a positive Pathergy test. The young adult is
      the most affected, usually in the third and fourth decades, with an exceptional
      onset after the age of 60 years. We report two cass of late onset Behcet's
      disease, occurring after the age of 70 years. The first case is a 70-year-old
      Lebanese male complaining of asymmetrical oligoarthritis, uveitis, oral
      ulcerations, ear chondritis, pseudofolliculitis and pustular rash, all
      corticosensitive. The second is the case of a 72-year-old Lebanese female who
      presented with posterior uveitis and retinal vasculitis, bipolar cutaneous
      ulcerations and a positive family history of Behcet's disease; all the symptoms
      were stabilized by immunosuppressive therapy. We discuss the differential
      diagnoses and the particularities of this late onset and emphasize the necessity
      of establishing an early diagnosis of Behcet's disease, even at an older age, and
      the need to start an adequate treatment in order to prevent serious ophtalmic and
      systemic complications.

PMID- 16904929
TI  - Osteoid osteoma of the carpal bones. Two case reports.
AB  - Osteoid osteoma rarely develops in the wrist. The symptoms resemble atypical
      tenosynovitis, with variations according to the location of the tumor. As a
      result, diagnostic wanderings are common. In addition, the pain may seem related
      to an injury, as illustrated by two cases reported herein. Conventional
      investigations often fail to contribute to the diagnosis. The most specific
      investigation is thin-slice computed tomography (CT), which can be coupled to
      magnetic resonance imaging. CT typically visualizes a round lucency surrounded by
      a rim of sclerosis; in addition, CT shows the exact location of the tumor,
      particularly relative to neighboring joints. Complete excision of the nidus must
      be achieved to ensure a permanent cure. Same-stage carpal bone fusion may be
      required in patients with extensive joint involvement.

PMID- 16904930
TI  - Enhanced hydrogen generation by particles during sonochemical decomposition of
      water.
AB  - A novel effect of any oxide particle/intermetallics enhancing hydrogen generation
      from water as compared to water alone when subjected to ultrasonic irradiation is
      reported here. Addition of methanol to water or decrease in particle size also
      improved the hydrogen yield. Hydrogen generation from water was further enhanced
      by the presence of both methanol and particles in water.

PMID- 16904931
TI  - Neighborhood characteristics and mental health among African Americans and whites
      living in a racially integrated urban community.
AB  - Aspects of the environment in which one lives are increasingly being recognized
      as major contributors to health, yet few empirical studies have focused on mental
      health. Therefore, we sought to determine if neighborhood characteristics were
      associated with mental health outcomes among 1408 African-American (59.3%) and
      white (40.7%) adults living in a socio-economically homogeneous, racially
      integrated, urban community in Baltimore, MD. Among African Americans and whites,
      the perception of severe problems in the community was associated with higher
      levels of stress (approximately 1.8 units higher), anxiety (approximately 1.8
      units higher), and depression (OR= approximately 2.0) compared to those who
      perceived no or few problems (all p<0.05). Community cohesion, the perception
      that people generally work together, was associated with better mental health
      among whites only. These findings give further insight into the complex
      environment of inner-city communities.

PMID- 16904932
TI  - High levels of antioxidant enzymatic defence assure good protection against
      hypoxic stress in spontaneously diabetic rats.
AB  - Recent data from literature report that reactive oxygen species (ROS) seem to
      play a crucial role in the etiology of both types I and II diabetes. This may
      render diabetic individuals more prone to oxidative injury when challenged with
      hypoxic stress. It is in fact well known that many diabetic complications cause
      ischaemic episodes, with a consequent reduction in oxygen supply to various
      tissues and organs. To check this hypothesis, in this work we tested type I
      diabetic individuals' antioxidant capability towards a hypoxic-mediated oxidative
      challenge. In particular, spontaneously diabetic and age-matched non-diabetic
      biobreeding (BB) Wistar rats were submitted to chronic normobaric hypoxia, and
      the response of antioxidant enzymes, as well as redox-sensitive transcription
      factor NF-kappaB and p53, were monitored. Results show that diabetic subjects
      present a dramatic enhancement in the major antioxidant enzymes activities, thus
      supporting the notion of diabetes-related changes in cellular redox status. This
      allows diabetic individuals to counteract hypoxia-mediated oxidative challenge
      better than the non-diabetic counterpart. Also the behaviour of both the redox
      sensitive nuclear transcription factor NF-kappaB and p53 protein in response to
      hypoxic stimulation seems to support the hypothesis of a better ROS scavenging
      efficiency in diabetics under hypoxic conditions. In conclusion, high levels of
      antioxidant enzymatic defences in diabetic BB rats reflect a positive adaptive
      response able to assure an efficient protection not only against chronic,
      diabetes-mediated reactive oxygen species (ROS) overproduction, but also versus
      further oxidative damage.

PMID- 16904933
TI  - Intra-subject elastic registration of 3D ultrasound images.
AB  - 3D registration of ultrasound images is an important and fast-growing research
      area with various medical applications, such as image-guided radiotherapy and
      surgery. However, this registration process remains extremely challenging due to
      the deformation of soft tissue and the existence of speckles in these images.
      This paper presents a technique for intra-subject, intra-modality elastic
      registration of 3D ultrasound images. Using the general concept of attribute
      vectors, we define the corresponding voxels in the fixed and moving images. Our
      method does not require presegmentation and does not employ any numerical
      optimization procedure. As the computational requirements are minimal, the method
      has potential use in real-time applications. The technique is implemented and
      tested on 3D ultrasound images of human liver, captured by a 3D ultrasound
      transducer. The results show that the method is sufficiently accurate and robust
      even in cases where artifacts such as shadows exist in the ultrasound data.

PMID- 16904934
TI  - Pentachlorophenol treatment in vivo elevates point mutation rate in zebrafish p53
      gene.
AB  - Pentachlorophenol (PCP), a probable human carcinogen, has been heavily used as an
      aseptic and a biocide throughout the world, and is widely present in the
      environment. Recent survey in Germany revealed that the average PCP amount in the
      urine of general German populations was 1.04 microg/L while the peak
      concentration could reach up to 19.1 microg/L. PCP was reported to cause DNA
      damage, but whether it can be involved in inducing point mutations in genome is
      unknown. To determine the genotoxicity of PCP on vertebrate, we first performed
      acute toxicity test on zebrafish for the effect of PCP exposure. The LC50 values
      of zebrafish exposed to PCP at 24, 48, 72 and 96 h were determined to be 0.196,
      0.130, 0.130 and 0.130 mg/L, respectively. We then treated zebrafish with PCP for
      10 days at 0 (control), 0.5, 5 and 50 microg/L, respectively, to determine
      whether PCP could be involved in inducing point mutations. Employing denaturing
      high-performance liquid chromatography analysis and DNA sequencing, we
      demonstrated that exposure of PCP to zebrafish at a concentration as low as 5
      microg/L for 10 days elevates point mutation rate in p53 gene in liver cells.
      This is the first direct evidence revealing that PCP can elevate point mutation
      rate in the vertebrate genomes. The result implies PCP might be involved in
      carcinogenesis by elevating point mutation rate in the somatic genomes.

PMID- 16904935
TI  - XRCC1 protects cells from chromate-induced chromosome damage, but does not affect
      cytotoxicity.
AB  - Hexavalent chromium Cr(VI) is a well known human carcinogen. This genotoxic metal
      induces DNA strand breaks and chromosome damage. However, the relationship
      between these lesions is uncertain. Our study focused on examining the role of
      XRCC1 in sodium chromate-induced cytotoxicity and chromosomal aberrations in
      Chinese Hamster Ovary (CHO) cells. Three different cell lines were used: AA8
      (parental), EM9 (XRCC1 mutant) and H9T3 (EM9 complemented with human XRCC1 gene).
      Results show that concentration-dependent decreases in relative survival are
      similar in all three cell lines, indicating that XRCC1 is not crucial for
      protecting cells from sodium chromate-induced cytotoxicity. Similarly the
      frequency of damaged metaphase cells was not affected by XRCC1 deficiency.
      However, the total number of Cr(VI)-induced chromosome aberrations was
      exacerbated by XRCC1 deficiency and the spectrum of chromosome damage changed
      dramatically. Specifically, chromatid and isochromatid lesions were the most
      prominent aberrations induced in the cell lines and XRCC1 was essential to reduce
      the formation of chromatid lesions. In addition, XRCC1 deficiency caused a
      dramatic increase in the number of chromatid exchanges indicating that it is
      involved in protection from Cr(VI)-induced chromosome instability.

PMID- 16904936
TI  - Long-term administering low anticoagulant activity heparin can lessen rat hepatic
      fibrosis induced by either CCl(4) or porcine serum injection.
AB  - BACKGROUND/AIM: Heparin or heparin-derived molecules have been demonstrated to
      have a renoprotective activity in a number of experimental nephropathies and anti
      fibrotic effect on pulmonary fibrosis induced by Bleomycin. However, the
      effectiveness of low anticoagulant activity heparin (LAAH) in the treatment of
      liver fibrosis has not been well defined. We are here demonstrating by both
      biochemical and morphological methods that long term LAAH administering can
      considerably decrease the hepatic fibrosis in rats elicited by carbon
      tetrachloride (CCl(4)) or injection of porcine serum. And its inhibition of
      fibrosis may be associated with the intervention of ERK signal transduction
      pathway and down-regulation of AP-1 activity in hepatic stellate cells. METHODS:
      LAAH were given to rats that subjected to CCl(4) or porcine serum injection
      induced liver fibrosis regimens up to 10 weeks. Immunohistochemical stainings for
      collagen types I and III plus image analysis as well as measurement of
      hydroxyproline content in the livers were carried out to evaluate the fibrosis of
      livers in rats. The activated HSCs (strong positive immunohistochemical staining
      for alpha-smooth actin) in the livers were counted under microscopy. The
      activities of extracellular signal-regulated kinase (ERK) in HSCs in vitro were
      estimated by the Western blot. Activator protein-1 (AP-1) activity in nuclear
      proteins of HSCs was measured by the electrophoresis motility shift assay (EMSA).
      RESULTS: The immunohistochemical staining plus image analysis showed that LAAH
      administration could reduce the contents of collagen types I and III to 16.48%
      and 27.94% of those in saline administration control in livers of rats treated
      with CCl(4) or 30.98% and 35.43% of those in saline administration control in
      livers of rats subjected to injection of porcine serum. Meanwhile, LAAH could
      decrease the content of hydroxyproline in the livers of rats treated with CCl(4)
      or injection of porcine serum by 32.83% or 32.41%, respectively. Long-term
      administration of LAAH can remarkably reduce the alpha-SMA positive cells only in
      the fibrotic livers induced by CCl(4). In vitro studies of HSCs showed that LAAH
      could inhibit the PDGF-BB augmented both expression and phosphorylation of ERK
      proteins and AP-1 activity in a dose-dependent manner. CONCLUSIONS: Long-term
      administering LAAH can suppress the hepatic fibrosis either induced by CCl(4) or
      injection of porcine serum. The mechanism of its anti-fibrotic effect may partly
      be related to the inference of ERK signal transduction pathway and AP-1 activity
      in activated hepatic stellate cells.

PMID- 16904937
TI  - Microneurography as a tool in clinical neurophysiology to investigate peripheral
      neural traffic in humans.
AB  - Microneurography is a method using metal microelectrodes to investigate directly
      identified neural traffic in myelinated as well as unmyelinated efferent and
      afferent nerves leading to and coming from muscle and skin in human peripheral
      nerves in situ. The present paper reviews how this technique has been used in
      clinical neurophysiology to elucidate the neural mechanisms of autonomic
      regulation, motor control and sensory functions in humans under physiological and
      pathological conditions. Microneurography is particularly important to
      investigate efferent and afferent neural traffic in unmyelinated C fibers. The
      recording of efferent discharges in postganglionic sympathetic C efferent fibers
      innervating muscle and skin (muscle sympathetic nerve activity; MSNA and skin
      sympathetic nerve activity; SSNA) provides direct information about neural
      control of autonomic effector organs including blood vessels and sweat glands.
      Sympathetic microneurography has become a potent tool to reveal neural functions
      and dysfunctions concerning blood pressure control and thermoregulation. This
      recording has been used not only in wake conditions but also in sleep to
      investigate changes in sympathetic neural traffic during sleep and sleep-related
      events such as sleep apnea. The same recording was also successfully carried out
      by astronauts during spaceflight. Recordings of afferent discharges from muscle
      mechanoreceptors have been used to understand the mechanisms of motor control.
      Muscle spindle afferent information is particularly important for the control of
      fine precise movements. It may also play important roles to predict behavior
      outcomes during learning of a motor task. Recordings of discharges in myelinated
      afferent fibers from skin mechanoreceptors have provided not only objective
      information about mechanoreceptive cutaneous sensation but also the roles of
      these signals in fine motor control. Unmyelinated mechanoreceptive afferent
      discharges from hairy skin seem to be important to convey cutaneous sensation to
      the central structures related to emotion. Recordings of afferent discharges in
      thin myelinated and unmyelinated fibers from nociceptors in muscle and skin have
      been used to provide information concerning pain. Recordings of afferent
      discharges of different types of cutaneous C-nociceptors identified by marking
      method have become an important tool to reveal the neural mechanisms of cutaneous
      sensations such as an itch. No direct microneurographic evidence has been so far
      proved regarding the effects of sympathoexcitation on sensitization of muscle and
      skin sensory receptors at least in healthy humans.

PMID- 16904938
TI  - Nucleolar apparatus in the macronucleus of Didinium nasutum (Ciliata): EM and 3D
      reconstruction.
AB  - The three-dimensional (3D) organization of nucleoli in the somatic nuclei
      (macronuclei) of recently fed and starved Didinium nasutum was reconstructed on
      the basis of serial ultra-thin sections. It was shown that nucleoli, looking on
      the single sections like individual separate structures, appeared to be parts of
      the large complicated branchy nucleolar networks. A 30 h starvation did not lead
      to disintegration of this network, but stimulated formation of numerous vacuoles
      in the granular component of nucleoli, which becomes more condensed. Unlike
      starved D. nasutum, in fed ciliates numerous holes appeared in the fibrillar
      component located at the periphery of nucleoli. These holes may presumably serve
      as channels for transporting newly synthesized rRNA. To our knowledge, this is
      the first report of a 3D reconstruction of the nucleolar apparatus in ciliates.

PMID- 16904939
TI  - Association of fucoxanthin chlorophyll a/c-binding polypeptides with photosystems
      and phosphorylation in the centric diatom Cyclotella cryptica.
AB  - Solubilization of thylakoid membranes of Cyclotella cryptica with dodecyl-beta
      maltoside followed by sucrose density gradient centrifugation or deriphate
      polyacrylamide gel electrophoresis resulted in the isolation of pigment protein
      complexes. These complexes were characterized by absorption and fluorescence
      spectroscopy, sodium dodecyl sulfate polyacrylamide gel electrophoresis and
      Western immunoblotting using antisera against fucoxanthin chlorophyll a/c-binding
      proteins and the reaction center protein D2 of photosystem II. Sucrose density
      gradient centrifugation yielded four bands. Band 1 consisted of free pigments
      with minor amounts of fucoxanthin chlorophyll a/c-binding proteins. Bands 2, 3,
      and 4 represented a major fucoxanthin chlorophyll a/c-binding protein fraction,
      photosystem II, and photosystem I, respectively. Deriphate polyacrylamide gel
      electrophoresis gave rise to five bands, representing photosystem I, photosystem
      II, two fucoxanthin chlorophyll a/c-binding protein complexes, and a band mostly
      consisting of free pigments. In the Western immunoblotting experiments, the
      specific association of two fucoxanthin chlorophyll a/c-binding proteins, Fcp2
      and Fcp4, to the photosystems could be demonstrated. In vivo experiments using
      antibodies against phosphothreonine residues and in vitro studies using [gamma
      32P]ATP showed that fucoxanthin chlorophyll a/c binding-proteins of 22 kDa became
      phosphorylated.

PMID- 16904940
TI  - Regulation of Salmonella pathogenicity island 2 genes by independent
      environmental signals.
AB  - The function of a type III secretion system (T3SS) encoded by Salmonella
      pathogenicity island 2 (SPI2) is essential for the intracellular lifestyle of
      Salmonella enterica serovar Typhimurium. Expression of SPI2 genes is induced
      within the Salmonella-containing vacuole (SCV) inside host cells and is
      controlled by the SsrAB two-component system. However, the nature of the signals
      leading to expression of SPI2 genes is controversial. Here we report that
      expression of SPI2 genes can be induced independently by two different
      environmental stimuli. Exposure of bacteria to slightly acidic pH was sufficient
      to induce a rapid up-regulation of SPI2 genes. In contrast, limitation of
      inorganic phosphate (P(i)) in the growth media led to activation of SPI2 genes in
      the late exponential growth phase and was independent of the media pH. Limitation
      of P(i) induced an over-expression of sensor protein SsrB. Response to both
      environmental stimuli required a functional SsrAB system. In vivo analyses
      indicated that limitation of P(i) is also encountered by intracellular
      Salmonella. Our observations allow the integration of previous disparate reports
      on the induction of SPI2 genes.

PMID- 16904941
TI  - What is Cryptosporidium? Reappraising its biology and phylogenetic affinities.
AB  - In raising the question "What is Cryptosporidium?", we aim to emphasize a growing
      need to re-evaluate the affinities of Cryptosporidium species within the phylum
      Apicomplexa so as to better understand the biology and ecology of these
      parasites. Here, we have compiled evidence from a variety of molecular and
      biological studies to build a convincing case for distancing Cryptosporidium
      species from the coccidia conceptually, biologically and taxonomically. We
      suggest that Cryptosporidium species must no longer be considered unusual or
      unique coccidia but rather seen for what they are--a distantly related lineage of
      apicomplexan parasites that are not in fact coccidia but that do occupy many of
      the same ecological niches. Looking at Cryptosporidium species without
      traditional coccidian blinders is likely to reveal new avenues of investigation
      into pathogenesis, epidemiology, treatment and control of these ubiquitous
      pathogens.

PMID- 16904942
TI  - Imaging in gynecology.
AB  - This chapter summarizes the diagnostic performance (sensitivity, specificity,
      positive and negative likelihood ratios) of ultrasound, computer tomography, and
      magnetic resonance imaging in the diagnosis of various gynecological diseases and
      tumors. Positron emission tomography is not discussed. Imaging in infertility, in
      the diagnosis of Mullerian duct anomalies and in gynecological oncology (staging
      of gynecological cancers, diagnosis of recurrence of gynecological cancer,
      diagnosis of trophoblastic tumors) is not dealt with. Ultrasound is the first
      line imaging method for discrimination between viable intrauterine pregnancy,
      miscarriage and tubal pregnancy in women with bleeding and/or pain in early
      pregnancy, for discrimination between benign and malignant adnexal masses and for
      making a specific diagnosis in adnexal tumors (e.g. dermoid cyst, endometrioma,
      hemorrhagic corpus luteum, etc.), for diagnosing intracavitary uterine pathology
      in women with bleeding problems, and for confirming or refuting pelvic pathology
      in women with pelvic pain. Magnetic resonance imaging can have a role as a
      secondary test in the diagnosis of adenomyosis, 'deep endometriosis' (e.g.
      endometriosis in the rectovaginal septum or in the uterosacral ligaments), and in
      the diagnosis of extremely rare types of ectopic pregnancy (e.g. in the spleen,
      liver or retroperitoneum).

PMID- 16904943
TI  - GAL4-NF-kappaB fusion protein augments transgene expression from neuronal
      promoters in the rat brain.
AB  - Targeted gene expression mediated by a mammalian cellular promoter is desirable
      for gene therapy in the brain, where there are a variety of different neuronal
      phenotypes, several types of supportive cells, and blood vessels. However, this
      approach can be hampered by weak activity of some cellular promoters. In view of
      the potency of the transcription factor NF-kappaB in regulating neuronal gene
      expression, we have assessed whether it can be used to enhance the strength of
      neuron-specific promoters. Our approach was to use a neuronal promoter to drive
      expression of a chimeric transactivator, which consisted of a part of the
      transcriptional activation domain of the NF-kappaB p65 protein fused to the DNA
      binding domain of GAL4 protein from yeast. The second copy of the neuronal
      promoter was modified by introducing the unique GAL4 binding sequences at its 5'
      end and used to drive the expression of a transgene. Binding of the chimeric
      transcriptional activator upstream of the second promoter was expected to
      potentiate its transcriptional activity. In this study, the approach was applied
      to the platelet-derived growth factor beta chain and synapsin-1 neuron-specific
      promoters and tested in vitro and in vivo using plasmid, lentiviral, and
      baculoviral vectors. We observed up to a 100-fold improvement in reporter gene
      expression in cultured neurons and 20-fold improvement in the rat brain in vivo.
      Moreover, the cell-type specificity of the two tested promoters was well
      preserved and restricted to neurons. Finally, the expression driven by the new
      lentiviral vectors with the p65-potentiated synapsin-1 promoter showed no signs
      of decline or cell damage 4 weeks after injection. This approach should be
      suitable for constructing powerful and stable gene expression systems based on
      weak cell-specific promoters in neuronal phenotypes.

PMID- 16904944
TI  - Targeted chromosomal gene modification in human cells by single-stranded
      oligodeoxynucleotides in the presence of a DNA double-strand break.
AB  - A DNA double-strand break (DSB) cannot be tolerated by a cell and is dealt with
      by several pathways. Here, it was hypothesized that DSB induction close to a
      targeted mutation in the genome of a mammalian cell might attract
      oligodeoxynucleotide (ODN)-directed gene repair. A HEK-293-derived cell line had
      been engineered harboring a single target locus with open reading frames encoding
      the living-cell reporter proteins LacZ and EGFP, the latter translationally
      decoupled by a DNA spacer with a unique I-SceI recognition site for defined DSB
      induction. To enable expression of a fluorescent LacZ-EGFP fusion protein, single
      stranded (ss) ODNs (80 or 96 nucleotides long) spanning the DSB were designed to
      fuse both reading frames by altering a few base-pair positions, deleting 59 bp or
      introducing a 10-bp fragment. The ssODNs alone generated few EGFP-positive cells.
      With I-SceI transiently expressed, more than 0.3% of cells revealed EGFP
      expression 7 days after transfection, with up to 96% of the loci faithfully
      corrected, depending on the ssODN used. During these correction events, the ssODN
      did not become physically incorporated into the chromosome, but served only as
      information template. Unwanted insertional mutagenesis also occurred. Both
      observations have important implications for gene therapy.

PMID- 16904945
TI  - Pathogenesis of Mycobacterium spp. in zebrafish (Danio rerio) from research
      facilities.
AB  - One of the most common diseases that we have diagnosed in zebrafish is
      mycobacteriosis, caused by several Mycobacterium spp. The severity of the disease
      ranged from severe outbreaks to incidental infections. We conducted an in vivo
      study to evaluate the pathogenesis of six isolates of Mycobacterium from
      zebrafish with mycobacteriosis from four research facilities and one wholesale
      supplier of zebrafish in the United States: Mycobacterium abscessus,
      Mycobacterium peregrinum, Mycobacterium chelonae (2 isolates), and Mycobacterium
      marinum. We also included two isolates of M. marinum from other fishes. Fish were
      exposed by intraperitoneal injection at a target does of 5 x 10(4) bacteria/fish,
      and were held in static aquaria at 28 degrees C for 8 weeks. Fish were examined
      by histology and culture, and mortalities were recorded. The M. marinum isolates
      caused 100% infection and mortality between 30% and 100%. None of the other
      Mycobacterium species caused significant mortalities, but several of these fish
      had granulomatous lesions in visceral organs. Mycobacteria were consistently
      recovered in culture from fish exposed to M. marinum, and from only 9% of fish
      exposed to the other species. This study suggests that, of the isolates tested,
      only M. marinum is highly pathogenic and virulent to healthy zebrafish.

PMID- 16904946
TI  - Metabolic and adipokine profile of Chinese patients with nonalcoholic fatty liver
      disease.
AB  - BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) and metabolic
      syndrome are reaching epidemic levels worldwide, but data in Asia remain scarce.
      This cross-sectional study examined the metabolic and adipokine profiles of
      Chinese patients with biopsy-proven NAFLD and factors associated with severe
      disease. METHODS: Eighty ethnic Chinese with NAFLD and 41 healthy controls were
      recruited. Metabolic parameters and fasting adiponectin, tumor necrosis factor
      alpha (TNF-alpha), leptin, and resistin levels were measured on the day of liver
      biopsy. Histology was scored according to Brunt's criteria. Metabolic syndrome
      was assessed by using both the International Diabetes Federation and Adult
      Treatment Panel III criteria. RESULTS: Twenty-eight patients had simple
      steatosis, and 52 patients had nonalcoholic steatohepatitis (NASH), defined as
      necroinflammatory grade >/=2 and/or fibrosis by Brunt's criteria. The ethnic
      specific International Diabetes Federation criteria identified more cases of
      metabolic syndrome among NAFLD patients than the Adult Treatment Panel III
      criteria (70% vs 56%, P < .0001). On multivariate analysis, low adiponectin
      level, increased leptin level, and diabetes mellitus were associated with NAFLD.
      High TNF-alpha level and high body mass index were independent factors associated
      with NASH. TNF-alpha level had positive correlation with necroinflammatory grade
      (R = .35, P = .002) and fibrosis stage (R = .31, P = .005). CONCLUSIONS:
      Hypoadiponectinemia and elevated TNF-alpha levels are associated with the
      development of NAFLD and NASH, respectively, independent of other metabolic
      factors. Ethnic-specific definition of metabolic syndrome is more useful in the
      assessment of NAFLD patients.

PMID- 16904947
TI  - Endometriosis with colonic wall invasion.

PMID- 16904948
TI  - Growth and nutritional status in infants with short-bowel syndrome after the
      serial transverse enteroplasty procedure.
AB  - BACKGROUND & AIMS: The aim of this study was to describe the long-term
      nutritional outcomes of 4 patients with short bowel syndrome (SBS) who underwent
      a newly described bowel-lengthening procedure, the serial transverse enteroplasty
      (STEP) procedure. METHODS: We performed a retrospective review of the medical
      records of 4 children who underwent STEP at 1 center. The primary outcome measure
      was the percentage of total dietary energy received by the enteral route before
      and after STEP. Other outcome measures were weight and height Z scores and body
      composition, as measured by arm anthropometric values. RESULTS: Four children
      with SBS were identified, all of whom had been dependent on parenteral nutrition
      since birth. The mean preoperative follow-up period was 234 days (range, 63-502
      days), and the mean postoperative follow-up period was 362 days (range, 252-493
      days). By using model-based mean estimates, the mean enteral nutrition intake was
      48% preoperatively vs 62% postoperatively (P = .02). The model mean weight for
      age Z score increased by .7 SDs postoperatively (P = .01), and the model mean
      weight for height increased by .6 SDs (P < .0001). The percent standard mid-upper
      arm circumference increased by 13.1% postoperatively (P = .03), and the percent
      standard triceps skinfold increased by 24.5% postoperatively (P < .0001).
      CONCLUSIONS: The STEP procedure was associated with improved growth and body
      composition among 4 children with SBS in the face of a decreasing need for
      parenteral nutrition. Among patients with refractory SBS and dilated small
      intestine, the STEP procedure is associated with improved clinical and
      nutritional outcomes in the first year after surgery.

PMID- 16904949
TI  - Esophageal ectopic sebaceous glands.

PMID- 16904950
TI  - Cholecystitis after metallic stent placement in patients with malignant distal
      biliary obstruction.
AB  - BACKGROUND & AIMS: Cholecystitis after metallic stent (MS) placement is an issue
      requiring attention. From our experience, cholecystitis seemed to occur mainly in
      patients with tumor involvement to the cystic duct orifice. The aim of the
      present study was to identify risk factors for cholecystitis in patients treated
      with covered or uncovered MS. METHODS: We analyzed 246 patients who received MS
      placement (covered MS in 171 and uncovered in 75) between August 1997 and May
      2005 for the treatment of unresectable distal malignant biliary obstruction.
      Causative diseases were as follows: pancreatic cancer in 162, papillary cancer in
      10, bile duct cancer in 41, and metastatic nodes in 33 patients. Tumor
      involvement to orifice of the cystic duct (OCD) was diagnosed based on
      cholangiography and intraductal ultrasonography. RESULTS: Cholecystitis after MS
      placement was found in 13 patients (5.3%). There was no significant difference in
      the incidence of cholecystitis between covered (5.8%) and uncovered (4.0%) MS. By
      univariate analysis, tumor involvement of the OCD, MS placed above the papilla,
      and stricture located at midportion were associated significantly with
      cholecystitis. By multivariate analysis, only tumor involvement of the OCD was a
      risk factor, with an odds ratio of 47.206 (95% confidence interval, 5.84-381.60).
      CONCLUSIONS: Cholecystitis after MS placement is associated with tumor
      involvement to the orifice of the cystic duct, regardless of the type of stent.

PMID- 16904951
TI  - A randomised trial of the effects of an additional communication strategy on
      recruitment into a large-scale, multi-centre trial.
AB  - Timely participant recruitment remains a significant challenge for most clinical
      trials. We evaluated the effects on participant recruitment of communication
      between the central trial coordinators and the clinical sites in the setting of a
      large international multi-centre clinical trial. The effects of communication
      were determined in a single-blind randomised controlled trial involving 167
      clinical sites in 19 countries. Clinical sites were randomised to either
      additional or usual communication strategies - the additional communication group
      received a communication package based on additional, individually-tailored
      feedback about recruitment, in addition to the usual correspondence from the
      central trial coordinators that was provided to the control group. The two study
      outcomes were the median time to half randomisation target and the median total
      number of participants randomised per clinical site. Eighty-five clinical centres
      were randomised to receive additional communication and 82 to receive usual
      communication. At the conclusion of recruitment, there was no significant
      difference in the median number of participants randomised per centre between the
      additional and usual groups (37.5 vs. 37.0, p=0.68). The median time to half
      randomisation target was lower in the additional communication group compared to
      the usual group, however this difference did not achieve conventional levels of
      statistical significance (4.4 months vs. 5.8 months, p=0.08). The findings
      suggest that the additional communication strategy may be of some incremental
      benefit in helping sites achieve recruitment targets sooner.

PMID- 16904952
TI  - Enhanced neuronal activation in central autonomic network nuclei in aged mice
      following acute peripheral immune challenge.
AB  - Infection is associated with activation in central autonomic nuclei involved in
      mediating coordinated host defense responses. Aged mice showed exaggerated
      sickness behavior following peripheral injection of pro-inflammatory bacterial
      lipopolysaccharide (LPS), but is unknown whether central autonomic network
      responses are concomitantly increased. To assess whether aged mice exhibit
      enhanced neural response to LPS, we compared neural responses using c-Fos
      immunohistochemistry in aged BALB/c mice (22-24 months) with those of young adult
      peers (3-6 months). Intraperitoneal LPS challenge induced robust expression of c
      Fos protein in central autonomic regions, including catecholaminergic neurons in
      the pons and brainstem, as well as in barrier-associated areas including the
      circumventricular organs. The numbers of c-Fos positive neurons were
      significantly greater in the aged compared to the young adult mice. These
      findings show age-associated enhancement of response to inflammation in the blood
      brain chemosensory interfaces as well the central autonomic pathways involved in
      the elaboration of sickness symptoms, which may contribute to exaggerated
      sickness and poorer outcomes of infectious disease in the elderly.

PMID- 16904953
TI  - Plasticity of neuroendocrine-thymus interactions during ontogeny and ageing: role
      of zinc and arginine.
AB  - Thymic re-growth and reactivation of thymic functions may be achieved in old
      animals by different endocrinological or nutritional manipulations such as, (a)
      treatment with melatonin, (b) implantation of a growth hormone (GH) secreting
      tumour cell line (GH3 cells) or treatment with exogenous GH, (c) castration or
      treatment with exogenous luteinizing hormone-releasing hormone (LHRH), (d)
      treatment with exogenous thyroxin or triiodothyronine, and (e) nutritional
      interventions such as arginine or zinc supplementation. These data strongly
      suggest that thymic involution is a phenomenon secondary to age-related
      alterations in neuroendocrine-thymus interactions and that it is the disruption
      of these interactions in old age that is responsible for age-associated immune
      neuroendocrine dysfunctions. The targets involved in hormones-induced thymic
      reconstitution may directly or indirectly involve hormone receptors, cytokines,
      arginine, and a trace element such as zinc, which is pivotal for the efficiency
      of neuroendocrine-immune network during the whole life of an organism. The effect
      of GH, thyroid hormones, and LHRH may be due to specific hormone receptors on
      thymocytes and on thymic epithelial cells (TECs), which synthesize thymic
      peptides. Melatonin may also act through specific receptors on T-cells. In this
      context, the role of zinc, which turnover is reduced in old age, is pivotal
      because of its involvement through zinc fingers in the gene expression of hormone
      receptors. In addition, the effects of zinc are multifaceted: from the
      reactivation of zinc-dependent enzymes, to cell proliferation and apoptosis, to
      cytokines expression and to the reactivation of thymulin, which is a zinc
      dependent thymic hormone required for intrathymic T-cell differentiation and
      maturation as well as for the homing of stem cells into the thymus. Zinc is also
      required for arginine action, via NO pathway. The role of zinc is therefore
      crucial in neuroendocrine-thymus interactions. According to data in animals and
      humans, the above reported endocrinological manipulations (GH, thyroid hormones,
      and melatonin) or arginine treatment may also act via zinc pool in restoring
      thymic activity in ageing allowing improvements on peripheral immune efficiency.

PMID- 16904954
TI  - Systems approaches to the networks of aging.
AB  - The aging of an organism is the result of complex changes in structure and
      function of molecules, cells, tissues, and whole body systems. To increase our
      understanding of how aging works, we have to analyze and integrate quantitative
      evidence from multiple levels of biological organization. Here, we define a
      broader conceptual framework for a quantitative, computational systems biology
      approach to aging. Initially, we consider fractal supply networks that give rise
      to scaling laws relating body mass, metabolism and lifespan. This approach
      provides a top-down view of constrained cellular processes. Concomitantly, multi
      omics data generation build such a framework from the bottom-up, using modeling
      strategies to identify key pathways and their physiological capacity. Multiscale
      spatio-temporal representations finally connect molecular processes with
      structural organization. As aging manifests on a systems level, it emerges as a
      highly networked process regulated through feedback loops between levels of
      biological organization.

PMID- 16904955
TI  - Analysis of nitrite and nitrate in biological samples using high-performance
      liquid chromatography.
AB  - Various analytical techniques have been developed to determine nitrite and
      nitrate, oxidation metabolites of nitric oxide (NO), in biological samples. HPLC
      is a widely used method to quantify these two anions in plasma, serum, urine,
      saliva, cerebrospinal fluid, tissue extracts, and fetal fluids, as well as meats
      and cell culture medium. The detection principles include UV and VIS absorbance,
      electrochemistry, chemiluminescence, and fluorescence. UV or VIS absorbance and
      electrochemistry allow simultaneous detection of nitrite and nitrate but are
      vulnerable to the severe interference from chloride present in biological
      samples. Chemiluminescence and fluorescence detection improve the assay
      sensitivity and are unaffected by chloride but cannot be applied to a
      simultaneous analysis of nitrite and nitrate. The choice of a detection method
      largely depends on sample type and facility availability. The recently developed
      fluorometric HPLC method, which involves pre-column derivatization of nitrite
      with 2,3-diaminonaphthalene (DAN) and the enzymatic conversion of nitrate into
      nitrite, offers the advantages of easy sample preparation, simple derivatization,
      stable fluorescent derivatives, rapid analysis, high sensitivity and specificity,
      lack of interferences, and easy automation for determining nitrite and nitrate in
      all biological samples including cell culture medium. To ensure accurate
      analysis, care should be taken in sample collection, processing, and
      derivatization as well as preparation of reagent solutions and mobile phases, to
      prevent environmental contamination. HPLC methods provide a useful research tool
      for studying NO biochemistry, physiology and pharmacology.

PMID- 16904956
TI  - The effect of the hexahistidine-tag in the oligomerization of HSC70 constructs.
AB  - The hexahistidine is a fusion tag used for the isolation of proteins via an
      immobilized metal-ion affinity chromatography (IMAC). In the present study, we
      have purified and analyzed two constructs of the heat shock protein HSC70 in the
      presence or the absence of the His-tag (C30WT-His(+)/C30WT and C30DeltaL
      His(+)/C30DeltaL). The oligomerization properties of the constructs were analyzed
      by size exclusion chromatography (SEC) and analytical ultracentrifugation (AU).
      Results from SEC analysis indicated that the His-tag promotes the dimerization of
      C30DeltaL-His(+) but has no effect on the elution profile of C30WT-His(+),
      compared to their respective untagged forms C30DeltaL and C30WT. These
      observations were also confirmed by AU analysis which indicates that C30DeltaL is
      stabilized in the dimeric form in the presence of the His-tag. These results
      emphasize the need to remove the His-tag before structural characterization of
      some recombinant proteins.

PMID- 16904957
TI  - Determination of total tiopronin in human plasma by LC-ESI-MS using tris (2
      carboxy-ethyl) phosphine as reducing reagent and methyl acrylate as
      derivatization reagent for the thiol group.
AB  - A quantitative method for the determination of total tiopronin (TP) in human
      plasma was developed by liquid chromatography with electrospray ionisation (ESI)
      mass spectrometric detection. After reduction with tris (2-carboxy-ethyl)
      phosphine (TCEP) and derivatization with methyl acrylate (MA) for the thiol group
      of TP, plasma samples were processed successively by deproteinization and solid
      phase extraction. N-acetyl-l-cysteine (NAC) was selected as internal standard
      undergoing the same treatment as TP. The method was validated that it could meet
      the need of biological analysis. The lower limit of quantitation (LLOQ) of TP in
      plasma was 0.02microg/mL. Finally, the method was successfully applied to a
      pharmacokinetic study in 20 healthy Chinese male volunteers after an oral dose of
      200mg TP tablets.

PMID- 16904958
TI  - A guest molecule-host cavity fitting algorithm to mine PDB for small molecule
      targets.
AB  - Inhaled anesthetic molecule occupancy of a protein internal cavity depends in
      part on the volumes of the guest molecule and the host site. Current algorithms
      to determine volume and surface area of cavities in proteins whose structures
      have been determined and cataloged make no allowance for shape or small degrees
      of shape adjustment to accommodate a guest. We developed an algorithm to
      determine spheroid dimensions matching cavity volume and surface area and applied
      it to screen the cavities of 6,658 nonredundant structures stored in the Protein
      Data Bank (PDB) for potential targets of halothane (2-bromo-2-chloro-1,1,1
      trifluoroethane). Our algorithm determined sizes of prolate and oblate spheroids
      matching dimensions of each cavity found. If those spheroids could accommodate
      halothane (radius 2.91 A) as a guest, we determined the packing coefficient.
      394,766 total cavities were identified. Of 58,681 cavities satisfying the fit
      criteria for halothane, 11,902 cavities had packing coefficients in the range of
      0.46-0.64. This represents 20.3% of cavities large enough to hold halothane, 3.0%
      of all cavities processed, and found in 2,432 protein structures. Our algorithm
      incorporates shape dependence to screen guest-host relationships for potential
      small molecule occupancy of protein cavities. Proteins with large numbers of such
      cavities are more likely to be functionally altered by halothane.

PMID- 16904959
TI  - Influence of bone volume fraction and architecture on computed large-deformation
      failure mechanisms in human trabecular bone.
AB  - Large-deformation bending and buckling have long been proposed as failure
      mechanisms by which the strength of trabecular bone can be affected
      disproportionately to changes in bone density, and thus may represent an
      important aspect of bone quality. We sought here to quantify the contribution of
      large-deformation failure mechanisms on strength, to determine the dependence of
      these effects on bone volume fraction and architecture, and to confirm that the
      inclusion of large-deformation effects in high-resolution finite element models
      improves predictions of strength versus experiment. Micro-CT-based finite element
      models having uniform hard tissue material properties were created from 54 cores
      of human trabecular bone taken from four anatomic sites (age = 70+/-11; 24 male,
      27 female donors), which were subsequently biomechanically tested to failure.
      Strength predictions were made from the models first including, then excluding,
      large-deformation failure mechanisms, both for compressive and tensile load
      cases. As expected, strength predictions versus experimental data for the large
      deformation finite element models were significantly improved (p < 0.001)
      relative to the small deformation models in both tension and compression. Below a
      volume fraction of about 0.20, large-deformation failure mechanisms decreased
      trabecular strength from 5-80% for compressive loading, while effects were
      negligible above this volume fraction. Step-wise nonlinear multiple regression
      revealed that structure model index (SMI) and volume fraction (BV/TV) were
      significant predictors of these reductions in strength (R2 = 0.83, p < 0.03).
      Even so, some low-density specimens having nearly identical volume fraction and
      SMI exhibited up to fivefold differences in strength reduction. We conclude that
      within very low-density bone, the potentially important biomechanical effect of
      large-deformation failure mechanisms on trabecular bone strength is highly
      heterogeneous and is not well explained by standard architectural metrics.

PMID- 16904961
TI  - The surgeon-scientist in a new biomedical research era.

PMID- 16904960
TI  - Changes in bone turnover and in bone mass in women with breast cancer switched
      from tamoxifen to exemestane.
AB  - Recently the third generation aromatase inhibitors have proved their efficacy and
      tolerability compared with tamoxifen in the adjuvant treatment of women with
      hormone responsive early breast cancer. However, there is some concern about the
      possible negative impact of these drugs on bone. The aim of the study was to
      evaluate the effects of the steroidal aromatase inactivator exemestane on bone
      turnover markers and on bone mineral density (BMD). Seventy postmenopausal women
      (62.0+/-8.9 years) with completely resected breast cancer and who were disease
      free following 2-3 years on tamoxifen were randomly assigned to continue
      tamoxifen (n=36) or switch to exemestane (n=34). Sixty-one patients completed the
      2-year study period. Bone alkaline phosphatase (B-ALP) and the carboxy-terminal
      telopeptide of type I collagen (CTX) were measured at baseline and after 3, 6, 9,
      12, 18 and 24 months. BMD at lumbar spine (BMD-LS), at femoral neck (BMD-FN), at
      total hip (BMD-T) and at whole body (BMD-WB) were measured at 6-monthly
      intervals. Exemestane-treated women showed significant (p<0.01) increases with
      respect to baseline in both B-ALP and CTX. The difference between the 2 groups
      reached the statistical significance at month 6 for CTX (p<0.05) and at month 9
      for B-ALP (p<0.01). Moreover, the exemestane-treated women showed an early
      decrease in PTH serum levels (-20.4%, p<0.01 at month 6). In the E group, the
      percentage changes were -2.37 (p<0.05) BMD-LS, -1.24 (p<0.05) BMD-FN, -1.1 (n.s.)
      BMD-T, -1.03 (n.s.) BMD-WB at month 12 and -2.99 (p<0.01) BMD-LS, -1.92 (p<0.01)
      BMD-FN, -2.01 (p<0.05) BMD-T, -1.3 (n.s.) BMD-WB at month 24. The tamoxifen group
      did not show significant changes in BMD. The differences between the two groups
      were significant at all skeletal sites except BMD-WB. Our data suggest that
      switching postmenopausal women from tamoxifen to exemestane causes a marked
      increase in bone turnover markers with a consequent reduction in BMD. These
      findings could be due to both the direct effect of exemestane and to the loss of
      the protective effect of tamoxifen. Therefore, the postmenopausal women switched
      from tamoxifen to exemestane should be monitored for bone loss especially if
      other risk factors for osteoporosis are present.

PMID- 16904962
TI  - Osteopontin inhibits macrophage nitric oxide synthesis to enhance tumor
      proliferation.
AB  - BACKGROUND: Interactions between tumor cells and their host environment can play
      a major role in regulating survival programs required for tumor progression.
      Osteopontin (OPN) is a glycophosphoprotein overexpressed by tumors, and is a key
      molecule for tumor progression and metastasis. OPN also inhibits expression of
      autocrine and paracrine inducible nitric oxide synthase (iNOS). Given the
      cytotoxic effects of macrophage NO expression, we hypothesized that tumor-derived
      OPN inhibits expression of local macrophage iNOS to potentiate tumor survival.
      METHODS: We used a coculture system of murine CT26 colorectal cancer cells with
      RAW264.7 murine macrophage cells. CT26 expresses OPN at high levels. RNA
      interference was utilized to produce long-term specific silencing of OPN in CT26.
      RESULTS: Inhibition of constitutive OPN synthesis in CT26 upregulates local NO
      production with inhibition of CT26 proliferation and promotion of CT26 apoptosis.
      Macrophage iNOS expression is accompanied by increased binding activity of
      nuclear factor-kappaB DNA. When the CT26 culture media were examined for a panel
      of proinflammatory cytokines, elevated concentrations of granulocyte colony
      stimulating factor (G-CSF) were found. Subsequently, in CT26 cells treated with
      antisense-G-CSF, NO levels in CT26-RAW cocultures were significantly decreased.
      CONCLUSION: In our system of CT26-RAW264.7 coculture, we conclude that inhibition
      of OPN synthesis in CT26 results in G-CSF-mediated induction of macrophage iNOS
      expression with resultant inhibition of CT26 proliferation via increased
      apoptosis. Our results suggest that tumor-derived OPN may enhance tumor survival
      by down regulating expression of NO in the local microenvironment. This is one
      mechanism by which OPN may potentiate cancer survival and progression.

PMID- 16904963
TI  - 17 beta-estradiol administration following trauma-hemorrhage prevents the
      increase in Kupffer cell cytokine production and MAPK activation predominately
      via estrogen receptor-alpha.
AB  - BACKGROUND: 17 beta-estradiol (E2) administration following trauma-hemorrhage (T
      H) attenuates the elevation in plasma cytokines and Kupffer cell (KC) cytokine
      production; however, it remains unknown whether the salutary effects are mediated
      via estrogen receptor (ER)-alpha or ER-beta. We hypothesized that E2 mediates its
      salutary effects via ER-alpha and normalization of MAPK under those conditions.
      METHODS: Male rats underwent T-H (mean blood pressure [BP] 40 mmHg for 90 min)
      and fluid resuscitation. ER-alpha agonist propyl pyrazole triol (PPT; 5
      microg/kg), ER-beta agonist diarylpropionitrile (DPN; 5 microg/kg), E2 (50
      microg/kg), or vehicle (10% DMSO) was injected subcutaneously during
      resuscitation. Twenty-four hours thereafter, KCs were isolated and their cytokine
      production (IL-6, TNF-alpha, IL-10) and MAPK activation were measured. RESULTS:
      Cytokine production increased after T-H, however, PPT or E2 administration after
      T-H normalized KC cytokine production. Although DPN attenuated increased
      production of these cytokines, KC capacity to produce the cytokines remained
      significantly higher than sham. PPT or E2 also prevented T-H-mediated activation
      of MAPK in KC. However, DPN did not prevent MAPK activation. CONCLUSIONS: Since
      PPT administration after T-H was more effective in decreasing KC cytokine
      production and MAPK activation than DPN, the salutary effects of E2 on KC
      functions are mediated predominantly via ER-alpha and normalization of MAPK
      following T-H.

PMID- 16904964
TI  - Bcl-XL antisense oligonucleotides coupled with antennapedia enhances radiation
      induced apoptosis in pancreatic cancer.
AB  - BACKGROUND: Pancreatic cancer is highly resistant to radiation and chemotherapy,
      and its resistance reflects the enhancement of apoptosis inhibitory genes,
      including Bcl-2 family. Antennapedia (pAnt) is capable of almost 100%
      internalization into cells through the lipid bilayer without any cytotoxic
      effect. The aim of this study was to examine the effects of the Bcl-XL antisense
      oligonucleotide for radiosensitivity of in vitro and in vivo pancreatic cancer
      using oligonucleotide conjugated with antennapedia. METHODS: In in vitro
      experiments, expression of Bcl-XL protein was examined in 5 pancreatic cancer
      cell lines. In AsPC-1 cells, internalization of the oligonucleotide was
      confirmed, and the effects of antennapedia-antisense (pAnt-AS) or antennapedia
      scramble (pAnt-Scr) on Bcl-XL protein expression were examined. Cells were
      treated with pAnt-AS, pAnt-Scr or phosphorothioate antisense (S-AS) for 3 days,
      then the effects of irradiation on the cell survival, caspase-3 activity, and
      apoptotic index were evaluated. In AsPC-1 xenograft mice, pAnt-AS, pAnt-Scr, or S
      AS was injected, and 5 or 10 Gy irradiation was added. Bcl-Xl protein expression
      was measured before irradiation. Apoptosis was evaluated at 48 hours after
      irradiation. On the 14th day after 10-Gy irradiation, tumor wet weight was
      measured, and tumor growth was estimated over 5 weeks. RESULTS: In in vitro
      experiments, all pancreatic cancer cell lines expressed Bcl-XL protein. pAnt-AS
      was internalized into AsPC-1 cells within 2 hours. pAnt-AS at 10 mumol/L reduced
      more than 90% of the Bcl-XL protein in AsPC-1 cells, whereas pAnt-Scr or S-AS
      treatment at the same concentration reduced as much as 10% of the Bcl-XL protein.
      Treatment with pAnt-AS followed by irradiation significantly reduced cell
      viability when compared with that of pAnt-Scr or S-AS. Caspase-3 activity was
      significantly upregulated in the pAnt-AS-treated group (P = .033). The rate of
      nuclear fragmentation was significantly higher in the pAnt-AS group (P = .013).
      In in vivo experiments, Bcl-XL protein was reduced about 40% in the pAnt-AS
      treated mice. Tumor doubling time of the pAnt-AS-treated mice was elongated by 10
      Gy irradiation. The tumor wet weight of mice treated with pAnt-AS and 10-Gy
      irradiation was significantly reduced when compared with mice treated with pAnt
      Scr and 10-Gy irradiation (P = .046). The apoptosis index at 48 hours after
      irradiation was significantly increased in pAnt-AS-treated mice (P < .01).
      CONCLUSIONS: The results suggest that, when coupled with antennapedia, the
      antisense oligonucleotide against Bcl-XL could be a good therapeutic tool for
      radiosensitization of pancreatic cancer.

PMID- 16904965
TI  - Up-regulation of TLK1B by eIF4E overexpression predicts cancer recurrence in
      irradiated patients with breast cancer.
AB  - BACKGROUND: The overexpression of eukaryotic initiation factor 4E (eIF4E), which
      is a critical component of the RNA helicase complex important in the translation
      of messenger RNAs with long and/or complex 5' untranslated regions, appears to
      impact malignant transformation and predict cancer recurrence in patients with
      breast cancer, independent of nodal status. Tousled-like kinase (TLK1B) is a
      mammalian threonine kinase with a long 5' untranslated regions in the messenger
      RNA. In vitro, malignant cells with eIF4E overexpression appear to have
      corresponding TLK1B elevation. Additionally TLK1B phosphorylates histone 3, which
      is a protein that is involved in chromatin assembly, plays an integral role in
      radioresistance in cell lines. Our hypothesis is that patients with breast cancer
      with high eIF4E overexpression have increased TLK1B and a higher risk for
      recurrence after adjuvant radiation therapy. METHODS: One hundred fifty-eight
      patients with stage I to III breast cancer were accrued in a prospective study
      that was designed to detect cancer recurrence in patients who had been treated
      with adjuvant radiation therapy. A standardized surveillance and treatment
      protocol was used to maximize treatment homogeneity and to detect the study
      primary end point, cancer recurrence. All patients received adjuvant radiation
      therapy either for high-risk node-positive disease or as a part of breast
      conservation therapy. TLK1B and eIF4E levels were quantified by Western blot.
      Statistical analysis was performed and included Spearman correlation, survival
      analysis by the Kaplan-Meier method, log-rank test, and Cox proportional hazard
      model. RESULTS: Both eIF4E (15.4 +/- 0.6, mean +/- SD) and TLK1B (18.8 +/- 1.5)
      were increased in all breast cancer specimens. Increasing eIF4E overexpression
      was correlated highly with increasing TLK1B (r = 0.35; P < .0001, Spearman
      coefficient). Tertile distribution of patients, based on the degree of eIF4E and
      TLK1B increase, demonstrated that the patients in the highest eIF4E group and the
      highest TLK1B group had a higher rate of cancer recurrences (P = .015 and .049,
      log rank test, respectively). After adjustment for stage of disease, age, and
      estrogen/progesterone receptor status, data showed that patients in the highest
      TLK1B group had a 3.0-fold increase in relative risk for cancer recurrence after
      adjuvant radiation therapy (P = .036; 95% CI, 1.0-5.0), compared with patients in
      the low TLK1B group. CONCLUSION: The overexpression of eIF4E is correlated with
      TLK1B increase in cancer specimens from patients with stage I to III breast
      cancer. High TLK1B increase in tumor specimens was associated with a higher risk
      for cancer recurrence after adjuvant radiation therapy. Resistance to
      radiotherapy may be 1 mechanism whereby eIF4E overexpression in breast cancer
      portends a worse prognosis.

PMID- 16904966
TI  - High-avidity antitumor T-cell generation by toll receptor 8-primed, myeloid-
      derived dendritic cells is mediated by IL-12 production.
AB  - BACKGROUND: High-level production of heterodimeric p70 interleukin (IL)-12 by
      myeloid-derived dendritic cells (DCs) requires 2 signals: interferon gamma (IFN
      gamma) and a maturation signal provided by CD40 ligation (CD40L) or
      lipopolysaccharide (LPS). METHODS: In the current study we demonstrate that
      signaling through toll-like receptor (TLR) 8, but not TLR3, TLR2, or TLR4,
      provides a priming signal to myeloid-derived DC for high IL-12 p70 heterodimer
      production. RESULTS: All the TLR agonists induced maturation of DC as evidenced
      by increased expression of CD83, CD80, and CD86. Both IFN-gamma and TLR7/8
      agonist R848 increased expression of TLR8 in immature monocyte-derived DCs. The
      combination of TLR7/8 agonist R848 and maturation signals LPS or CD40L induced
      high-level expression of IL-12p35 and p40 similar to that induced by IFN-gamma
      plus LPS. In contrast, receptor agonists specific for TLR7 did not prime for IL
      12 production. The p70 IL-12 produced by the TLR8-primed DC polarized CD4+ T for
      Th1 cytokine production and induced CD8+ T cells, displaying high functional
      avidity with enhanced tumor cell recognition. CONCLUSIONS: The data suggest that
      toll 8 receptor agonists are useful for inducing type-1 polarized DCs for vaccine
      design in treating cancer and infectious disease.

PMID- 16904967
TI  - Low-dose carbon monoxide inhalation prevents ischemia/reperfusion injury of
      transplanted rat lung grafts.
AB  - BACKGROUND: Carbon monoxide (CO), a byproduct of heme catalysis by heme
      oxygenases, has been shown to provide protection against ischemia/reperfusion
      (I/R) injury. We examined the cytoprotective effect of CO at a low concentration
      on cold I/R injury of transplanted lung grafts. METHODS: Orthotopic left lung
      transplantation was performed in syngenic Lewis to Lewis rat combination. Grafts
      were preserved in University of Wisconsin solution at 4 degrees C for 6 hours.
      Donors and/or recipients were exposed to CO (250 ppm) in air for 1 hour before
      surgery and then continuously post-transplantation. RESULTS: Blood oxygen partial
      pressure of graft pulmonary veins in the CO-treated group versus the air-treated
      group was significantly higher. The increase of messenger RNA of inflammatory
      mediators such as interleukin-6, tumor necrosis factor-alpha, inducible nitric
      oxide synthase, and cycloooxygenase-2 was markedly inhibited in the CO-treated
      group. The expression of phosphorylated-extracellular signal-regulated protein
      kinase 1/2 was significantly reduced in the CO-treated group. CO treatment
      reduced the number of infiltrating macrophages into the lung grafts. Vascular
      endothelial cells detected by CD31 stain were well preserved in CO-treated
      grafts, while those in air-treated grafts were faint and interrupted.
      CONCLUSIONS: These results demonstrate that exogenous low-dose CO treatment of
      donors and recipients can prevent lung I/R injury and significantly improve
      function of lung grafts after extended cold preservation and transplantation.

PMID- 16904968
TI  - Pentoxifylline attenuates stored blood-induced inflammation: A new perspective on
      an old problem.
AB  - BACKGROUND: Blood transfusion is a risk factor for many inflammatory processes.
      Its supernatant fraction has been proven to activate neutrophils. We hypothesized
      that pentoxifylline (PTX) would attenuate stored blood-induced neutrophil
      activation and pro-inflammatory mediator production. METHODS: Whole blood was
      incubated with HBSS, LPS (100 microg/mL), leukoreduced PRBC supernatant + LPS, or
      supernatant + LPS + PTX (2 mmol/L). TNF-alpha levels were measured by ELISA. MMP
      9 was evaluated with zymography. Neutrophil CD66b expression was determined by
      flow cytometry in blood treated with HBSS, fMLP (1 micromol/L), supernatant +
      fMLP, or supernatant + fMLP + PTX. RESULTS: TNF-alpha levels were elevated in
      both the LPS and supernatant + LPS groups (100%; P < 0.01 and 120%; P < 0.01,
      respectively). PTX administration resulted in a 106% decrease in TNF-alpha (P <
      0.0001). MMP-9 levels were increased in all groups. Administration of PTX to the
      supernatant + LPS group generated a 33% decrease in MMP-9 levels, which was not
      statistically significant (P < 0.4). Upregulation of CD66b expression was seen in
      LPS and supernatant + LPS groups. Significant attenuation was seen with PTX (47%;
      P < 0.01). CONCLUSIONS: PTX downregulates CD66b and TNF-alpha expression in
      supernatant-induced whole blood. Because blood transfusion can contribute to
      inflammatory injury, the adjunctive use of PTX may have therapeutic potential.

PMID- 16904969
TI  - Bradykinin induces microvascular preconditioning through the opening of calcium
      activated potassium channels.
AB  - BACKGROUND: This study was designed to investigate whether the activation of
      calcium-activated potassium (K(Ca)) or adenosine triphosphate sensitive potassium
      (K(ATP)) channels are required for bradykinin-induced microvascular
      preconditioning. METHODS: Isolated rabbit hearts underwent retrograde perfusion
      with Krebs-Henseleit buffer (KHB) followed by 60 minutes of ischemic arrest with
      cold crystalloid cardioplegia (CCCP). Eight CCCP hearts received no pretreatment.
      Six bradykinin-preconditioned hearts received a 10-minute coronary infusion of
      10(-8) mol/L bradykinin-enriched KHB followed by a 5-minute recovery period
      before CCCP. Six hearts received both 10(-8) mol/L charybdotoxin (a K(Ca) channel
      blocker) and bradykinin preconditioning. Finally, 6 other hearts received 10(-5
      degrees ) mol/L glibenclamide (a K(ATP) channel blocker) to bradykinin-enriched
      KHB. All hearts were reperfused for 30 minutes with KHB. RESULTS: Bradykinin
      preconditioning significantly improved the recovery of left ventricular and
      microvascular function, as compared with control. On the other hand, bradykinin
      preconditioning significantly reduced the contractile responses to U46619, a
      thromboxane A2 analogue. Charybdotoxin significantly inhibited the improved
      recovery of bradykinin-induced left ventricular and microvascular function.
      Glibenclamide tended to diminish the bradykinin preconditioning-enhanced recovery
      of left ventricular function, but failed to affect bradykinin preconditioning
      improved recovery of microvascular function. CONCLUSION: Both K(Ca) and K(ATP)
      channels were involved partially in bradykinin-induced myocardial
      preconditioning. However, bradykinin induces microvascular preconditioning
      through the opening of K(Ca) channels rather than K(ATP) channels.

PMID- 16904970
TI  - Patient-reported outcomes after inguinal herniorrhaphy.
AB  - BACKGROUND: Patient-reported outcomes (PRO) reflect the functional outcomes of
      inguinal herniorrhaphy. We studied the effect of hernia recurrence and
      complications on PRO for participants in the Veterans Affairs trial of Open or
      Laparoscopic Repair of Inguinal Hernia. METHODS: Analyzed PRO included (1) the
      Medical Outcomes Study Short Form 36, version 2, (2) the Surgical Pain Scale, (3)
      the Activities Assessment Scale, and (4) patient satisfaction. Recurrences and
      complications were recorded at follow-up visits. Complications were categorized
      by (1) hematoma/seroma, (2) orchitis, (3) neuralgia, and (4) other. Univariate
      and multivariable regression analyses identified variables significantly
      associated with postoperative PRO. RESULTS: Of the 1603 patients with PRO data,
      105 had a recurrence and 342 had a complication at 2 years. Multivariable
      analyses showed neuralgia (P < .0005) adversely affected all PRO, and recurrence
      (P < .05) affected patient-reported pain, activity, and satisfaction, but not the
      score for the Medical Outcomes Study Short Form 3. Patients with a recurrence
      after open repair had more pain than those with a recurrence after laparoscopic
      repair (P = .0001). Patients with other complications after laparoscopic repair
      reported more pain and less activity than those with other complications after
      open repair (P = .003 and P = .009, respectively). CONCLUSIONS: The effectiveness
      of inguinal herniorrhaphy should be measured by the rate of recurrence and
      neuralgia. Postoperative neuralgias have a deleterious effect on all patient
      reported outcomes.

PMID- 16904971
TI  - Implementation of a novel web-based objective structured clinical evaluation.
AB  - BACKGROUND: This study was performed to identify factors that impact student
      performance on a web-based objective structured clinical evaluation (OSCE) that
      was developed to improve the evaluation process of students who complete a fourth
      year surgical clerkship in trauma-critical care. METHODS: We created a multiple
      choice OSCE with commercially available software. Clinical cases were developed
      for incorporation into 7 quizzes that were assembled to appear as 1 examination.
      Students used intensive care unit flow sheets to review data, to develop a
      systems-based problem list and differential diagnoses, and to produce treatment
      recommendations. RESULTS: No difference was noted in a comparison of the mean
      scores that were achieved by students on a previous paper (essay format) OSCE and
      the new web OSCE. There was a correlation of student performance on the web OSCE
      to the National Board of Medical Examiners (NBME) subject examination that had
      been completed the previous year (r = 0.60; P < .0001). Performance on the NBME
      subject examination was the only independent factor that affected reporter,
      interpreter, and manager skills that were assessed by the OSCE (P < .01).
      CONCLUSION: Implementation of a web OSCE resulted in similar performance of the
      class as compared with performance on the previous paper OSCE. Correlation of
      student achievement on the web OSCE to the NBME subject examination supported the
      construct validity of this institutional examination beyond the areas of face and
      content validity in which OSCEs may excel.

PMID- 16904972
TI  - Enterogenesis in a clinically feasible model of mechanical small-bowel
      lengthening.
AB  - BACKGROUND: Recent work indicates that mechanical force induces small-bowel
      growth, although methods reported do not have direct clinical application. We
      report a clinically feasible technique of enterogenesis and describe intestinal
      function in this model. METHODS: Using a pig model (n = 11), we stretched
      isolated small intestinal segments mechanically for 7 days in vivo with an
      intraluminal device. Control segments were not stretched. Morphology, histology,
      and epithelial proliferation were assessed. Absorption and epithelial barrier
      function were examined in an Ussing chamber. RESULTS: Stretch segments were
      significantly longer than Control segments and had nearly 2-fold greater surface
      area (P < .001). Mucosal thickness was much greater in Stretch than Control
      segments (772 +/- 134 vs. 647 +/- 75 microm, P = .02). Although villus height was
      reduced in Stretch and Control segments (353 +/- 76 vs. 324 +/- 76 microm, P =
      .6) versus native jejunum (522 +/- 87, P < .0005), crypt depth was increased
      dramatically in Stretch (450 +/- 95 microm) versus Control segments (341 +/- 64,
      P = .005). This observation was accompanied by a 2-fold increase in cellular
      proliferation (26.3 +/- 3.8 vs 12.1 +/- 6.6 % bromodeoxyuridine+, P < .05).
      Barrier function was intact ([3H]-mannitol permeation, 0.16 +/- 0.08%, vs native
      jejunum, 0.17 +/- 0.08%, P = .81). Glucose-mediated sodium transport was similar
      in Stretch versus native jejunum segments (60.0 +/- 23.5 vs 82.3 +/- 47.3
      microA/cm2, P = .31), as was carbachol-induced chloride transport (82.4 +/- 72.2
      vs 57.2 +/- 33.4 microA/cm2, P = .54) and alanine absorption (16.46 +/- 12.94 vs
      23.53 +/- 21.31 microA/cm2, P = .53). CONCLUSIONS: Mechanical stretching induces
      small intestinal growth, while maintaining function. Epithelial architecture does
      change, such that a decrease in villus height is offset by a marked increase in
      crypt depth and a 2-fold increase in epithelial proliferation. Epithelial barrier
      and absorptive functions remain intact. The device described may have direct
      clinical applicability.

PMID- 16904973
TI  - C-Reactive protein and inflammatory response associated to neurocognitive decline
      following cardiac surgery.
AB  - BACKGROUND: It has been recognized that neurocognitive decline (NCD) often occurs
      as a complication in cardiac surgery. The early inflammatory response and C
      reactive protein (CRP) was examined in relation to NCD and to a marker of axonal
      central nervous system (CNS) injury after cardiopulmonary bypass. METHODS: A
      cohort of patients undergoing coronary artery bypass grafting and/or valve
      procedures using cardiopulmonary bypass were administered a neurocognitive
      battery preoperatively and postoperatively at 6 hours and day 4. CRP, interleukin
      1 beta, and interleukin 10 were quantified from serum. Increase of serum tau
      protein after surgery was used as a marker of axonal CNS damage. RESULTS: The
      rate of NCD was found to be 40.5% in this group. Surprisingly, known predictors
      of NCD did not differ significantly between patients with/without NCD. Patients
      with NCD had an early increase of CRP of a significantly higher magnitude than
      those without NCD (38.01 +/- 11.4 vs 16.49 +/- 3.5 mg/L, P = .042), interleukin
      1ss (2.35 +/- 0.3 vs 1.20 +/- 0.2 pg/mL, P = .002), and interleukin 10 (29.77 +/-
      4.7 vs 12.94 +/- 2.2 pg/mL, P < .001). Increase in serum Tau protein was
      significantly correlated to NCD (r = 0.50, P = .02). CONCLUSION: Perioperative
      increases in CRP and inflammatory cytokines are associated with NCD in patients
      after cardiopulmonary bypass. Thus, it appears that inflammation plays a key role
      in NCD pathophysiology, likely via axonal CNS injury, and could become a target
      for prevention.

PMID- 16904974
TI  - Efficacy of zoledronate against neuroblastoma.
AB  - BACKGROUND: We investigated the antitumor and antiosteoclastic effects of
      zoledronate against human neuroblastoma in vitro and in a murine model of bone
      metastasis. METHODS: Antitumor activity of zoledronate against neuroblastoma cell
      lines was assessed by evaluating proliferation, apoptosis, and cell-cycle
      progression. A murine model of bone invasion was used to assess antiosteoclastic
      and antitumor activity in vivo. Mice were followed by radiographic and
      bioluminescence imaging. RESULTS: Treatment of human neuroblastoma cells resulted
      in a decrease in cell count, increase in apoptosis, and arrest of cell-cycle
      progression. In the model of bone invasion, mice were treated weekly with
      zoledronate or vehicle control 10 days after tumor cell inoculation. Five weeks
      later, radiographs revealed a large degree of osteolytic disease in control mice.
      Impressively, mice treated with zoledronate demonstrated minimal radiographic
      changes at this time. Bioluminescence imaging of these mice revealed a
      significant restriction of tumor growth during the course of therapy.
      CONCLUSIONS: Zoledronate exhibits significant antitumor activity against human
      neuroblastoma cells in vitro, prevents development of osteolytic lesions, and
      restricts tumor growth in a murine model of bone metastasis. These results
      suggest that clinical investigation of zoledronate or similar bisphosphonates as
      adjuvant therapy in neuroblastoma patients is warranted.

PMID- 16904975
TI  - CD40 ligand increases expression of its receptor CD40 in human coronary artery
      endothelial cells.
AB  - BACKGROUND: Recently, CD40 ligand (CD40L) and its receptor CD40 have been
      implicated in atherosclerosis. Clinical data showed that elevated CD40L levels
      are associated with a high risk of cardiovascular events. The aim of this study
      was to investigate whether CD40L could affect the expression of its membrane
      receptor CD40 as a feedback mechanism by which CD40L could enhance its functions
      in human coronary artery endothelial cells (HCAECs). METHODS: The HCAECs were
      treated with human soluble CD40L, and the messenger RNA (mRNA) and protein levels
      of CD40 were determined by real-time polymerase chain reaction and Western blot
      analysis, respectively. The specific effect of CD40L was confirmed by a blocking
      experiment with antibody against CD40L. Involvements of oxidative stress and
      mitogen-activated protein kinases (MAPKs) were also studied with antioxidant
      seleno-L-methionine (SeMet) and MAPK inhibitors such as extracellular signal
      regulated kinase 1/2 (ERK1/2) inhibitor. RESULTS: When HCAECs were cultured with
      CD40L (5 microg/mL) for 24 hours, CD40 mRNA levels were increased by 79% compared
      with controls (P < .05). Similarly, Western blot analysis showed an 80% increase
      in CD40 protein levels (P < .05). The CD40L-induced increase in CD40 mRNA levels
      were blocked specifically by anti-CD40L antibody. Antioxidant SeMet and specific
      ERK1/2 inhibitor (PD98059) also effectively blocked CD40L-induced CD40 mRNA
      increase. CONCLUSIONS: These data demonstrate that clinically relevant
      concentration of CD40L increased the expression of its receptor CD40 in HCAECs.
      The CD40L-induced upregulation of CD40 may be mediated by oxidative stress and
      ERK1/2 activation. This study suggests a new mechanism by which CD40L could
      enhance its biologic functions in the vascular system and contribute to
      endothelial dysfunction and vascular disease.

PMID- 16904976
TI  - Secretoneurin increases monolayer permeability in human coronary artery
      endothelial cells.
AB  - BACKGROUND: Secretoneurin (SN), a novel neuropeptide, may play a role in
      inflammation in the vascular system. However, the interaction between SN and
      endothelial cells is largely unknown. This study's objective is to investigate
      the effects of SN on endothelial permeability and its associated molecular
      mechanisms in human coronary artery endothelial cells (HCAECs). METHODS: HCAECs
      were treated with SN. Monolayer permeability was assayed with a transwell system
      and a Texas Red-labeled dextran tracer. The mRNA and protein levels of
      endothelial junctional molecules were determined by real-time reverse
      transcriptase polymerase chain reaction (RT-PCR) and Western blot analysis,
      respectively. Superoxide anion was determined by fluorescent dye dihydroethidium
      based flow cytometry detection. Mitogen-activated protein kinase (MAPK)
      activation was determined by Bio-Plex immunoassay. RESULTS: HCAECs were treated
      with SN (15, 30, and 60 ng/ml) for 24 hours and showed a significant increase of
      monolayer permeability by 12%, 33%, and 47%, respectively, compared with controls
      (P < 0.05). SN-treated cells showed a significant reduction of zonula occludens-1
      (ZO-1) and occludin at both mRNA and protein levels (P < 0.05). In addition, SN
      significantly increased superoxide anion in HCAECs (P < 0.05). Furthermore, SN
      activated MAPKs (JNK and ERK1/2) but not p38. Both antioxidant seleno-L
      methionine (SeMet) and specific inhibitors of JNK and ERK1/2 effectively blocked
      SN-induced monolayer permeability increase in HCAECs. CONCLUSIONS: SN
      significantly increases monolayer permeability and reduces the expression of ZO-1
      and occludin through oxidative stress and the activation of JNK and ERK1/2 in
      HCAECs. This study provides direct evidence that SN impairs endothelial barrier
      function.

PMID- 16904977
TI  - Psychomotor testing predicts rate of skill acquisition for proficiency-based
      laparoscopic skills training.
AB  - BACKGROUND: Laparoscopic simulator training translates into improved operative
      performance. Proficiency-based curricula maximize efficiency by tailoring
      training to meet the needs of each individual; however, because rates of skill
      acquisition vary widely, such curricula may be difficult to implement. We
      hypothesized that psychomotor testing would predict baseline performance and
      training duration in a proficiency-based laparoscopic simulator curriculum.
      METHODS: Residents (R1, n = 20) were enrolled in an IRB-approved prospective
      study at the beginning of the academic year. All completed the following: a
      background information survey, a battery of 12 innate ability measures (5 motor,
      and 7 visual-spatial), and baseline testing on 3 validated simulators (5
      videotrainer [VT] tasks, 12 virtual reality [minimally invasive surgical trainer
      virtual reality, MIST-VR] tasks, and 2 laparoscopic camera navigation [LCN]
      tasks). Participants trained to proficiency, and training duration and number of
      repetitions were recorded. Baseline test scores were correlated to skill
      acquisition rate. Cutoff scores for each predictive test were calculated based on
      a receiver operator curve, and their sensitivity and specificity were determined
      in identifying slow learners. RESULTS: Only the Cards Rotation test correlated
      with baseline simulator ability on VT and LCN. Curriculum implementation required
      347 man-hours (6-person team) and 795,000 dollars of capital equipment. With an
      attendance rate of 75%, 19 of 20 residents (95%) completed the curriculum by the
      end of the academic year. To complete training, a median of 12 hours (range, 5.5
      21), and 325 repetitions (range, 171-782) were required. Simulator score
      improvement was 50%. Training duration and repetitions correlated with prior
      video game and billiard exposure, grooved pegboard, finger tap, map planning, Rey
      Figure Immediate Recall score, and baseline performance on VT and LCN. The map
      planning cutoff score proved most specific in identifying slow learners.
      CONCLUSIONS: Proficiency-based laparoscopic simulator training provides
      improvement in performance and can be effectively implemented as a routine part
      of resident education, but may require significant resources. Although
      psychomotor testing may be of limited value in the prediction of baseline
      laparoscopic performance, its importance may lie in the prediction of the
      rapidity of skill acquisition. These tests may be useful in optimizing curricular
      design by allowing the tailoring of training to individual needs.

PMID- 16904978
TI  - Robotic minimally invasive mitral valve reconstruction yields less blood product
      transfusion and shorter length of stay.
AB  - BACKGROUND: Robotic-assisted minimally invasive mitral valve reconstruction has
      gained popularity recently. Initial reports suggest that this approach can be
      used with relative safety and efficacy. Direct comparisons with a traditional
      sternotomy approach have not yet been explored extensively. METHODS: All mitral
      valve procedures that were performed by a single surgeon during a 3-year period
      of time were analyzed (n = 142 procedures). Patients whose condition required
      concomitant coronary artery bypass grafting or aortic valve surgery were excluded
      subsequently from analysis, because all of these patients were approached
      obligatorily by sternotomy (n = 71 patients). Six patients underwent right
      thoracotomy mitral valve procedures without robotic assistance, and 1 patient in
      cardiogenic shock underwent emergent mitral valve reconstruction by sternotomy.
      Of the remaining 64 patients who were eligible theoretically for sternotomy or
      robotic-assisted minimally invasive surgery, 39 patients underwent sternotomy,
      and 25 patients underwent right chest minimally invasive robotic-assisted
      surgery. Randomization between these 2 approaches would be almost impossible in
      the United States. The primary determinant for the choice of approach was request
      of the referring physician or patient. Multiple perioperative outcomes were then
      compared. RESULTS: Patients who underwent sternotomy and robotic-assisted surgery
      exhibited equivalent preoperative characteristics and experienced an equivalent
      degree of correction of mitral regurgitation in repairs and in need for
      replacement. Complex mitral valve repairs that entailed leaflet resection and
      reapproximation, annular plication, sliding annuloplasty, chordal transfer, and
      GoreTex neochordal construction were accomplished successfully with the robotic
      system. Cross-clamp and bypass times were longer for patients in the minimally
      invasive group (110 vs 151 minutes; P = .0015; 162 vs 239 minutes; P < .001,
      respectively). Mean packed red blood cell transfusion was lower among patients
      who underwent robotic-assisted surgery (5.0 vs 2.8 units; P = .04). Patients who
      underwent robotic-assisted surgeries experienced shorter mean duration of
      postoperative hospitalization (10.6 vs 7.1 days; P = .04). There was 1 death
      among the patients who underwent sternotomy, and no deaths among the patients who
      underwent robotic-assisted surgery. CONCLUSION: Patients can undergo mitral valve
      reconstruction with minimally invasive robotic assistance, avoid a sternotomy,
      require less blood product transfusion, and experience shorter hospitalization.

PMID- 16904979
TI  - Clathrin heavy chain is required for TNF-induced inflammatory signaling.
AB  - BACKGROUND: Tumor necrosis factor receptor I recruits tumor necrosis factor
      receptor-associated death domain (TRADD) and multiple kinases that ultimately
      phosphorylate inhibitor kappa B (IKB alpha). Degradation of phospho-IKB alpha (p
      IKB alpha) frees nuclear factor kappa B (NFKB) to be active and phosphorylated.
      Many receptors require clathrin-mediated endocytosis to provide the scaffolds
      necessary for signaling. Therefore, we investigated the role of clathrin heavy
      chain (CHC) in tumor necrosis factor alpha (TNF-alpha)-induced IKB alpha
      phosphorylation and NFKB activation. We hypothesized that CHC was required for
      TNF-alpha-induced inflammatory signaling. METHODS: We treated human pulmonary
      epithelial cells with small interfering RNA to knock down intracellular CHC
      (CHCsil). TRADD and scrambled (noncoding) small interfering RNA sequences were
      used as positive and negative controls, respectively. Treatment groups were
      exposed to 10 ng/mL of TNF-alpha. Total I kappaB alpha, p-I kappaB alpha, and
      phosphorylated P65 (a subunit of NFKB) were determined by immunoblot staining.
      Densitometry was normalized to controls for the analysis of the stains. TNF-alpha
      induced release of monocyte chemoattractant protein 1 (MCP-1) was determined by
      enzyme-linked immunosorbent assay. Statistical analyses were determined by
      analysis of variance or paired t test as appropriate. RESULTS: TNF-alpha-induced
      I kappaB alpha phosphorylation and degradation at 5 and 30 minutes, respectively,
      and induced P65 phosphorylation. CHCsil diminished p-I kappaB alpha by 91% (P <
      .03); however, I kappaB alpha degradation was not affected. CHC knockdown caused
      a 66% decrease in P65 phosphorylation after 3 minutes of TNF-alpha. CHCsil
      decreased TNF-alpha-induced MCP-1 by 46% (P < .05), compared with control.
      CONCLUSIONS: CHCsil significantly impairs phosphorylation of both I kappaB alpha
      and P65. CHCsil also significantly decreased MCP-1 production. These data suggest
      that CHC is required for certain TNF-alpha-induced, inflammatory signaling
      pathways.

PMID- 16904980
TI  - Forced expression of PDX-1 induces insulin production in intestinal epithelia.
AB  - BACKGROUND: In the developmental stage, pancreas derives from the endodermal
      cells where the transcription factor, pancreatic duodenal homeobox gene-1 (pdx-1)
      is expressed. In adulthood, pdx-1 expression is localized to pancreatic beta
      cells, which is necessary for maintenance of beta cell function. Recently,
      ectopic expression of pdx-1 in the liver successfully induced insulin production
      and ameliorated hyperglycemia. Our study was designed to investigate the effects
      of forced expression of pdx-1 in ileal epithelia by adenovirus-mediated gene
      transfer. METHODS: The recombinant, replication-deficient adenovirus carrying the
      pdx-1 gene was constructed using the COS-TPC method. ICR mice were treated with
      intraperitoneal injection of 220 mg/kg streptozotocin (STZ). After determining
      the hyperglycemia, a loop of ileum was constructed and the adenovirus solutions
      (Ad-pdx-1 and Ad-lacZ 1 x 10(8) PFU/body) were injected into the lumen of the
      ileal loop. In this model, immunohistochemical or fluorescent analyses of PDX-1
      and insulin in the adenovirus-infected ileal epithelia were carried out. Reverse
      transcription polymerase chain reaction of pdx-1 and other pancreatic markers
      were investigated. Blood glucose concentrations were measured by drawing blood
      from ocular veins. Immunoreactive insulin extracted from the adenovirus-infected
      ileum was measured. RESULTS: Ad-pdx-1 induced ectopic PDX-1 expression in the
      ileum. The PDX-1 positive cells in the ileal epithelia were positive for insulin;
      mRNA of insulin-1, insulin-2 and pdx-1 were expressed in mice infected with Ad
      pdx-1. Hyperglycemia was improved in STZ-treated mice infected with Ad-pdx-1.
      Immunoreactive insulin in the ileum extract was increased significantly in mice
      with Ad-pdx-1. CONCLUSIONS: Gene transfer of PDX-1 in intestinal epithelia could
      be a promising strategy for diabetes mellitus by inducing ectopic insulin
      producing cells.

PMID- 16904981
TI  - Abrogation of recurrent autoimmunity in the NOD mouse: A critical role for host
      interleukin 4.
AB  - BACKGROUND: We previously established a clinically relevant strategy to abrogate
      recurrent autoimmunity and enable long-term islet graft survival, involving
      antilymphocyte serum (ALS)-depletion of recipient T cells and intraportal
      administration of donor pancreatic lymph node cells (PLNCs) along with islet
      grafts. In this study, we investigated whether Th2 cytokines were required for
      the tolerizing ability of ALS/PLNC treatment in islet transplantation. METHODS:
      ALS-treated diabetic NOD recipient mice, and NOD recipient mice deficient in
      interleukin 4 (IL-4-/-) or 10 (IL-4/10-/-) were transplanted with NOR or NOD.scid
      islets intraportally along with donor PLNC. Blood glucose levels were monitored
      to access graft function, sections of graft-bearing livers were histologically
      examined, and ELISPOT assays were used to assess cytokine profile and frequency
      of islet-reactive CD4 T cells. RESULTS: We found that ALS/PLNC was not effective
      in prolonging islet graft survival in diabetic NOD hosts deficient in either IL-4
      (NOD.IL-4-/-) or in IL-4 and IL-10 (NOD.IL4-/-/10-/-) (mean survival time, 36
      days), contrasting the long-term survival of islet grafts in wild-type NOD mice
      (mean survival time, > 80 days). In contrast, PLNC deficient in IL-4 promoted
      long-term graft survival in wild-type NOD hosts similar to that in wild-type
      PLNC. In wild-type NOD recipients of either wild-type PLNC or IL-4-/- PLNC, the
      host autoantigen-specific CD4 T cells produced predominately IL-4 coincident with
      long-term graft survival, whereas, in NOD.IL-4-/- recipients with rejected
      grafts, the autoreactive T cells produced interferon gamma and low amounts of IL
      4. CONCLUSIONS: These data demonstrate that abrogation of recurrent autoimmunity
      requires host IL-4 and that manipulation of the autoreactive cytokine profile in
      long-term diabetes may be an effective strategy for islet transplant therapies.

PMID- 16904982
TI  - Angiotensin II and tumor necrosis factor-alpha upregulate survivin and Kruppel
      like factor 5 in smooth muscle cells: Potential relevance to vein graft
      hyperplasia.
AB  - BACKGROUND: Survivin (SVV) is a unique inhibitor of apoptosis protein (IAP) that
      regulates both apoptosis and mitosis. Recent work suggests that SVV plays a
      critical role in the vascular injury response, but the molecular pathways remain
      unclear. METHODS: We examined the expression of SVV and the transcription factor,
      KLF5, in human venous smooth muscle cells (VSMC) by semi-quantitative reverse
      transcriptase polymerase chain reaction (RT-PCR) and Western blot analysis after
      treatment with angiotensin II (Ang II) or tumor necrosis factor-alpha (TNF
      alpha). An adenoviral construct expressing SVV or GFP was also employed to assess
      effects on KLF5 expression. A rabbit carotid interposition vein graft model was
      used to assess the relevance of KLF5 to bypass graft healing. RESULTS:
      Stimulation of VSMC with Ang II and TNF-alpha led to a rapid upregulation of KLF5
      expression, and a later increase in SVV, which was cell-cycle independent.
      Overexpression of SVV in VSMC led to an early and persistent induction of KLF5.
      KLF5 was upregulated in rabbit vein grafts early (1 day) after grafting.
      CONCLUSIONS: We speculate that SVV is a central point of convergence of multiple
      signaling pathways in vascular injury, and that it regulates the local
      amplification of these pathways in the vessel wall.

PMID- 16904984
TI  - Profound hypothermia is superior to ultraprofound hypothermia in improving
      survival in a swine model of lethal injuries.
AB  - BACKGROUND: Rapid induction of profound hypothermia can improve survival from
      uncontrolled lethal hemorrhage. However, the optimal depth of hypothermia in this
      setting remains unknown. This experiment was designed to compare the impact of
      deep (15 degrees C), profound (10 degrees C), and ultraprofound (5 degrees C)
      hypothermia on survival and organ functions. METHODS: Uncontrolled lethal
      hemorrhage was induced in 32 swine (80-120 lb) by creating an iliac artery and
      vein injury, followed 30 minutes later by laceration of the descending thoracic
      aorta. Hypothermia was induced rapidly (2 degrees C/min) by infusing cold organ
      preservation solution into the aorta through a thoracotomy. The experimental
      groups were (n = 8 per group): a normothermic control, and 3 hypothermic groups
      in which the core temperature was reduced to 15 degrees C, 10 degrees C, and 5
      degrees C. Vascular injuries were repaired during 60 minutes of hypothermia.
      Animals were then rewarmed (0.5 degrees C/min) and resuscitated on
      cardiopulmonary bypass, and monitored for 6 weeks for neurologic deficits,
      cognitive function, and organ dysfunction. RESULTS: All normothermic animals
      died, whereas 6-week survival rates for the 15 degrees C, 10 degrees C, and 5
      degrees C groups were 62.5%, 87.5%, and 25%, respectively (P < .05: normothermic
      vs 15 degrees C and 10 degrees C; 10 degrees C vs 5 degrees C). The surviving
      animals from the 15 degrees C and 10 degrees C groups were neurologically intact,
      displayed normal learning capacity, and had no long-term organ dysfunction. The
      survivors from the 5 degrees C group displayed slower recovery and impaired
      cognitive functions. CONCLUSIONS: In a model of lethal injuries, rapid induction
      of profound hypothermia can prevent death. The depth of hypothermia influences
      survival, with a better outcome associated with a core temperature of 10 degrees
      C compared with 5 degrees C.

PMID- 16904983
TI  - Interferon alpha and CPG oligodeoxynucleotides elicit additive immunostimulatory
      and antitumor effects.
AB  - BACKGROUND: We hypothesized that interferon alpha (IFN-alpha) and unmethylated
      cytosine-phosphothioate-guanine (CpG)-rich oligodexoynucleotides (CpG ODNs) would
      elicit potent antitumor activity due to the ability of this treatment combination
      to activate complimentary signal transduction intermediates. METHODS: Peripheral
      blood mononuclear cells treated with CpG ODNs, IFN-alpha, or both agents combined
      were evaluated for cytotoxicity against human melanoma cells, Jak-STAT signal
      transduction by flow cytometry, and ISG-15 gene expression by real-time
      polymerase chain reaction. The effects of CpG ODNs and IFN-alpha were evaluated
      in murine models of melanoma in wild-type, IFN-gamma-deficient, and STAT1
      deficient mice. Negative controls in all experiments included treatment with
      control ODN or phosphate-buffered saline. RESULTS: Treatment of peripheral blood
      mononuclear cells with a combination of CpG ODNs and IFN-alpha resulted in
      enhanced cytotoxicity, activation of natural killer cells, IFN-alpha-induced
      STAT1 phosphorylation, and transcription levels of ISG-15. These
      immunostimulatory effects of CpG ODNs were associated with increased expression
      of STAT1 and STAT2 proteins. Administration of CpG ODNs plus IFN-alpha elicited
      superior antitumor activity in a murine model of B16 melanoma compared with
      either agent alone. The antitumor properties of CpG ODNs were dependent on STAT1
      mediated signal transduction within the host but independent of endogenously
      produced IFN-gamma. CONCLUSIONS: CpG ODNs represent potent immune stimulants that
      elicit antitumor effects through STAT1-mediated signal transduction.

PMID- 16904985
TI  - Mesenchymal stem cells enhance xenochimerism in NK-depleted hosts.
AB  - BACKGROUND: Xenogeneic hematopoietic engraftment holds promise as a strategy to
      achieve whole organ xenograft tolerance. We tested whether xenogeneic bone marrow
      grafts, engineered with mesenchymal stem cells (MSCs), might provide a new
      nontoxic approach to enhance xenogeneic engraftment. METHODS: ACI rat MSCs,
      cultured from whole bone marrow, were identified as CD29+ CD44+OX-18+, CD45-HIS36
      and could differentiate into adipogenic and osteogenic tissue. Lethally
      irradiated B6 mice received ACI whole bone marrow either alone or in combination
      with ACI MSC. Xenogeneic engraftment was measured in murine peripheral blood on
      days 7, 50, and 100. Natural killer (NK)-cell-depleted murine recipients treated
      with or without MSC underwent rat skin graft transplants on the day of the bone
      marrow infusion. RESULTS: In NK-depleted hosts, control animals failed to survive
      60 days; 40% MSC-treated hosts survived >100 days, P < 0 .05. Rat hematopoietic
      engraftment exceeded 89% on days 7 and 54 and decreased to <25% by day 100. No
      graft-versus-host disease was observed in MSC-treated animals, P < 0.05. Skin
      graft survival was prolonged in the MSC-treated group, (21 +/- 1.7 days, P =
      0.2). CONCLUSIONS: Our findings present a new approach in engineering xenografts
      and provide an encouraging platform for additional studies.

PMID- 16904986
TI  - TGF-beta inhibits Akt-induced transformation in intestinal epithelial cells.
AB  - BACKGROUND: During the early stages of colorectal carcinogenesis, the
      phosphatidylinositol 3-kinase (PI3K)/Akt pathway is activated, enabling the
      transformed cells to survive and grow in the absence of anchorage to
      extracellular matrix. Transforming growth factor beta (TGF-beta) is an important
      tumor suppressor in the colon, and it is inactivated during later stages of
      colorectal carcinogenesis. The purpose of this study was to determine whether TGF
      beta inhibits Akt-induced anchorage-independent growth and resistance to anoikis
      in gut epithelial cells. METHODS: Rat intestinal epithelial cells (RIE-1) were
      infected with a retrovirus containing pLXSN-mAkt, and three independent clones
      were selected. Anchorage-independent growth was examined by colony formation in
      soft agar and cell counting in ultralow attachment plates. Anoikis was analyzed
      with the use of Annexin V staining. RESULTS: All three clones of RIE-1/mAkt
      formed colonies in soft agar, which were decreased by TGF-beta. TGF-beta induced
      anoikis and treatment with a general caspase inhibitor, zVAD-fluoromethyl ketone,
      blocked TGF-beta-mediated decrease in colony formation. CONCLUSIONS: TGF-beta
      attenuated Akt-induced anchorage-independent growth in RIE-1 cells in part by
      enhancing anoikis. Our data demonstrate a novel tumor-suppressor activity of TGF
      beta and provide the molecular justification for the required activation of the
      PI3K/Akt pathway and the subsequent inactivation of TGF-beta signaling during
      colorectal carcinogenesis.

PMID- 16904990
TI  - Thoracic spine extradural arteriovenous fistula: case report and review of the
      literature.
AB  - BACKGROUND: Spinal extradural arteriovenous fistula is a rare, disabling, but
      potentially treatable disease. Only 27 cases have been reported so far in the
      past 40 years. CASE DESCRIPTION: An 18-year-old adolescent girl developed
      repeated back pain and mild paraplegia after a training course. Magnetic
      resonance imaging revealed a vessel-like lesion at the spinal extradural space,
      compressing the spinal medulla at the T5 level. Angiography disclosed a focal
      fistula fed by branches of the intercostal artery. The vascular mass was
      surgically removed and confirmed pathologically. CONCLUSION: Spinal extradural
      arteriovenous fistulas have an arterial supply that originates outside the spinal
      dura, with venous draining into the spinal extradural venous plexus. They may
      lead to myelopathy, radiculopathy, or spontaneous extradural hematoma, due to
      dilated vein compression, blood stealing, or spinal venous hypertension.
      Extradural hematoma needs emergency laminectomy and clot evacuation. And
      extradural arteriovenous fistulas should be treated actively by embolization,
      surgical resection, or both. Appropriate treatment will stabilize the patient or
      result in neurological improvement.

PMID- 16904988
TI  - Treatment of lesions involving both the infratemporal fossa and middle skull
      base.
AB  - BACKGROUND: Communicating occupying lesions of the intratemporal fossa and mid
      cranial fossa represent challenges for neurosurgeons and maxillofacial surgeons.
      Lesions of the skull base, with complex anatomy, are extremely varied in their
      histopathology. They often spread via normal anatomic pathways or bony
      destruction to involve adjacent structures, especially in the case of malignant
      neoplasms. However, with the development of operative skills and reconstruction
      techniques, total or near total resection of many such lesions can be
      accomplished with a low morbidity rate. METHODS: The combined frontotemporal
      preauricular infratemporal approach, frontotemporal-orbitozygomatic approach,
      combined frontotemporal and transmandibular approach, transmandibular approach,
      and transmaxillary approach were used to resect the lesions using microsurgical
      skills. The plastic reconstruction included reconstruction of the dura defects,
      osteosynthesis, and obliteration of the operative cavity. RESULTS: Thirty-three
      patients with communicating lesions invading both the infratemporal fossa and the
      middle skull base underwent microsurgery. Among them, lesions were totally
      resected in 23, subtotally resected in 6, and partially resected in 4. In 29
      patients, clinical status improved significantly. Complications were encountered
      in 7 cases, and morbidity was not remarkable. CONCLUSION: The surgical approach
      should be selected depending on the size, location, histopathology, and invading
      extension of the lesion, which can provide excellent visualization and allow for
      an aggressive and safe resection of lesions involving this region. Familiarity
      with skull base anatomy, careful microsurgical manipulation, protection of vital
      structures, reliable plastic reconstruction, intraoperative nerve monitoring, as
      well as consideration of functional and esthetic outcomes, will all contribute to
      successful surgery and satisfactory results.

PMID- 16904991
TI  - Microsurgical experience with keyhole operations on intracranial aneurysms.
AB  - BACKGROUND: We report our experience with keyhole approaches as favorable
      treatments for various intracranial aneurysms including multiple aneurysms and
      giant aneurysms. METHODS: According to the different locations of 105 aneurysms
      harbored in 100 patients, different keyhole approaches were designed elaborately,
      among which a supraorbital keyhole approach was used in 91 cases, a pterional
      keyhole approach in 5 cases, a subtemporal keyhole approach in 3 cases, a
      retromastoid keyhole approach in 2 cases, and a unifrontal interhemispheric
      keyhole approach in 1 case. RESULTS: Among those 105 aneurysms, 99 were clipped
      successfully, including 4 that were resected after clipping. One mini-aneurysm
      was wrapped. The other aneurysms were trapped, including 1 VA aneurysm, 1 giant
      ICA aneurysm, 1 giant PCoA aneurysm, and 2 giant aneurysms in the PCAs (P2-P3
      segment). Multiple aneurysms in 5 cases were treated in 1 surgical session,
      including 3 cases via unilateral approaches and 2 cases via bilateral approaches.
      There were no severe keyhole approach-related complications in this present
      series. CONCLUSION: The keyhole approaches, based on improvements in diagnostic
      imaging, advanced surgical instruments, and microsurgical skills, are effective
      and ideal craniotomy techniques in the hands of experienced neurosurgeons for the
      treatment of intracranial aneurysms, including multiple and giant aneurysms, in
      patients without diffuse SAH, severe cerebral vasospasm, and severe brain edema
      or brain swelling.

PMID- 16904993
TI  - A study on the relationship between HLA-DR, DQ antigen, and intracranial aneurysm
      in the Han nationality.
AB  - BACKGROUND: To investigate the relationship between HLA-DR, DQ antigen, and
      intracranial aneurysm in the Han nationality. METHODS: We compared the occurrence
      of HLA-DR and HLA-DQ antigens in patients with intracranial saccular aneurysm and
      in the control group by PCR and agarose gel electrophoresis. RESULTS: No
      statistically significant correlation between HLA-DR, HLA-DQ antigen frequency,
      and the pathogenesis and clinical characteristics of intracranial aneurysm has
      been found. CONCLUSIONS: We have not found any relationship between HLA-DR and
      HLA-DQ antigen frequency, haplotype frequency, and pathogenesis and clinical
      characteristics of intracranial aneurysm, but the patients who presented with HLA
      DR53, DR52, DQ7(3), and DQ5(1) seem to be more likely to bear multiple
      intracranial aneurysms.

PMID- 16904996
TI  - Microvascular density and vascular endothelial growth factor have little
      correlation with prognosis of craniopharyngioma.
AB  - BACKGROUND: Craniopharyngioma is histologically a benign epithelial tumor located
      in the supersellar cistern that often presents aggressive growth and repeated
      recurrence. The authors hypothesized that craniopharyngioma recurrence and
      invasive growth are angiogenesis dependent and evaluated the significance of
      vascularization in the prognosis of craniopharyngioma by a prospective cohort
      study. METHODS: The cohorts consisted of 32 patients with AE and 31 patients with
      SP tumor. The primary and recurrence removal specimens of the cohort patients
      were gathered. Microvascular density and VEGF protein in the recurrence group and
      recurrence-free group were detected by the immunohistochemistry avidin-biotin
      peroxidase method and analyzed quantitatively through computer-assisted
      microscopy to evaluate the correlation of MVD and VEGF with prognosis of
      craniopharyngiomas. RESULTS: The average follow-up phase was 63.34 months; 14 of
      32 patients with AE and 6 of 31 patients with SP had recurrence and underwent
      operation again. Although MVD and VEGF have significant difference between AE and
      SP (P=.000, P=.018, respectively), MVD and VEGF have no statistical difference
      between the recurrence group and recurrence-free group (P>.05). CONCLUSIONS:
      Microvascular density and VEGF in craniopharyngioma tissue have no correlation
      with prognosis of the tumor, which may be explained by the minimal blood
      circulation in the craniopharyngioma. Adamantine epithelioma showed more tendency
      to recur than SP.

PMID- 16904997
TI  - It is time for urgent action on the Lebanese health crisis.

PMID- 16904998
TI  - Planning for Cuba's transition.

PMID- 16904999
TI  - Taming trachoma.

PMID- 16905002
TI  - Persistent organic pollutants and the burden of diabetes.

PMID- 16905000
TI  - Overview of randomised trials of ACE inhibitors.

PMID- 16905001
TI  - QTc prolongation: methadone's efficacy-safety paradox.

PMID- 16905003
TI  - UK classification of drugs of abuse: an un-evidence-based mess.

PMID- 16905005
TI  - Food industry and health: mostly promises, little action.

PMID- 16905004
TI  - Managing the risks of facial transplantation.

PMID- 16905008
TI  - Tadataka Yamada: new leader in global health.

PMID- 16905010
TI  - Researching minority groups.

PMID- 16905009
TI  - Health of the world's Roma population.

PMID- 16905011
TI  - Health of the world's Roma population.

PMID- 16905013
TI  - Injury-related mortality and indigenous people.

PMID- 16905012
TI  - Anticonvulsants for protracted seizures in children.

PMID- 16905014
TI  - Defective acute inflammation in Crohn's disease.

PMID- 16905016
TI  - Who controls the controllers?

PMID- 16905017
TI  - Defective acute inflammation in Crohn's disease.

PMID- 16905018
TI  - Female genital mutilation.

PMID- 16905020
TI  - European Union health systems and the case of Yvonne Watts.

PMID- 16905021
TI  - EU alcohol policies and free trade: consequences beyond its borders.

PMID- 16905022
TI  - Angiotensin-converting-enzyme inhibitors in stable vascular disease without left
      ventricular systolic dysfunction or heart failure: a combined analysis of three
      trials.
AB  - BACKGROUND: Angiotensin-converting-enzyme (ACE) inhibitors reduce cardiovascular
      mortality and morbidity in patients with heart failure or left ventricular
      systolic dysfunction (LVSD). Three large trials have assessed the effect of ACE
      inhibitors in stable patients without these conditions but with atherosclerosis.
      We undertook a systematic review of the Heart Outcomes Prevention Evaluation
      (HOPE), the European trial on Reduction Of cardiac events with Perindopril among
      patients with stable coronary Artery disease (EUROPA), and the Prevention of
      Events with ACE inhibition (PEACE) studies to determine the consistency with
      which ACE inhibitors reduce total mortality and fatal and non-fatal
      cardiovascular events. METHODS: We computed cardiovascular outcomes and total
      mortality in the 29,805 patients of these three trials, randomly assigned an ACE
      inhibitor or placebo and followed up for a mean of about 4.5 years. The results
      were also analysed within the context of five large trials of ACE inhibitors in
      patients with heart failure or LVSD. FINDINGS: When the findings of the HOPE,
      EUROPA, and PEACE trials were combined, ACE inhibitors significantly reduced all
      cause mortality (7.8 vs 8.9%, p=0.0004), cardiovascular mortality (4.3 vs 5.2%,
      p=0.0002), non-fatal myocardial infarction (5.3 vs 6.4%, p=0.0001), all stroke
      (2.2 vs 2.8%, p=0.0004), heart failure (2.1 vs 2.7%, p=0.0007), coronary-artery
      bypass surgery (6.0 vs 6.9%, p=0.0036) but not percutaneous coronary intervention
      (7.4 vs 7.6%, p=0.481). The composite outcomes of cardiovascular mortality, non
      fatal myocardial infarction, or stroke occurred in 1599 (10.7%) of the patients
      allocated ACE inhibitor and in 1910 (12.8%) of those allocated placebo (odds
      ratio, 0.82; 95% CIs 0.76-0.88; p<0.0001). Except for stroke and
      revascularisation, these results were similar to those of the five trials in
      patients with heart failure or LVSD. INTERPRETATION: ACE inhibitors reduce
      serious vascular events in patients with atherosclerosis without known evidence
      of LVSD or heart failure. Results showing these benefits in intermediate-risk
      patients complement existing evidence of similar benefit in higher-risk patients
      with LVSD or heart failure. Therefore, use of ACE inhibitors should be considered
      in all patients with atherosclerosis.

PMID- 16905023
TI  - Effect of 3 years of SAFE (surgery, antibiotics, facial cleanliness, and
      environmental change) strategy for trachoma control in southern Sudan: a cross
      sectional study.
AB  - BACKGROUND: A trachoma control programme was started in southern Sudan in 2001.
      We did a 3-year evaluation to quantify uptake of SAFE (surgery, antibiotics,
      facial cleanliness, and environmental change) interventions, and to assess the
      prevalence of active trachoma and unclean faces. METHODS: Cross-sectional
      surveys, including clinical assessment of trachoma (WHO simplified system) and
      structured questionnaires, were done in four intervention areas at baseline and
      follow-up. Process indicators were uptake of SAFE components; primary outcome
      indicators included trachomatous inflammation-follicular (TF) and unclean face in
      children aged 1-9 years. FINDINGS: There was heterogeneous uptake of SAFE between
      intervention areas. Surgical coverage was low in all areas (range 0.5% of 428
      individuals in Katigiri to 6% of 5002 in Kiech Kuon), antibiotic uptake ranged
      from 14% of 1257 individuals in Kiech Kuon to 75% of 954 in Katigiri, health
      education ranged from 49% of 190 households in Kiech Kuon to 90% of 182 in Padak,
      and latrine coverage from 3% of households in Tali to 16% in Katigiri.
      Substantial decreases in prevalence of TF and unclean faces were recorded in
      Katigiri and Tali, two of three sites where uptake of antibiotics and health
      education was high: TF decreased by 92% (95% CI 87-96) and 91% (86-95),
      respectively, and unclean face decreased by 87% (78-94) and 38% (22-52),
      respectively. Moderate effects were recorded in Padak, an area with high
      coverage, with a 28% (14-41) decrease in TF and a 16% (7-25) decrease in unclean
      face. No evidence of decline was seen in Kiech Kuon, where uptake of antibiotics
      and health education was low, with a 2% (-10 to 12) decrease in TF and a 10% (-3
      to 23) decrease in unclean face. INTERPRETATION: Our results show that
      substantial falls in active trachoma can occur where SAFE is implemented, and
      that good results could be achieved with the SAFE strategy in other trachoma
      endemic areas.

PMID- 16905025
TI  - Recurrent miscarriage.
AB  - Many human conceptions are genetically abnormal and end in miscarriage, which is
      the commonest complication of pregnancy. Recurrent miscarriage, the loss of three
      or more consecutive pregnancies, affects 1% of couples trying to conceive. It is
      associated with psychological morbidity, and has often proven to be frustrating
      for both patient and clinician. A third of women attending specialist clinics are
      clinically depressed, and one in five have levels of anxiety that are similar to
      those in psychiatric outpatient populations. Many conventional beliefs about the
      cause and treatment of women with recurrent miscarriage have not withstood
      scrutiny, but progress has been made. Research has emphasised the importance of
      recurrent miscarriage in the range of reproductive failure linking subfertility
      and late pregnancy complications and has allowed us to reject practice based on
      anecdotal evidence in favour of evidence-based management.

PMID- 16905024
TI  - Intensive insecticide spraying for fly control after mass antibiotic treatment
      for trachoma in a hyperendemic setting: a randomised trial.
AB  - BACKGROUND: There are no data on the cumulative effect of fly control and
      antibiotic distribution on trachoma in hyperendemic communities. We sought to
      determine whether insecticide spray intervention after mass antibiotic treatment
      could reduce trachoma and ocular infection with Chlamydia trachomatis in
      hyperendemic neighbourhoods in Tanzania. METHODS: We did a single-blind,
      randomised clinical trial in 16 neighbourhoods (balozi) in Kongwa, Tanzania. All
      children aged 1-7 years were enrolled, with 119 children in the eight balozi of
      the intervention group and 183 in the eight control balozi. Children were
      examined at baseline, 6 months, and 1 year for clinical trachoma and ocular C
      trachomatis infection. One dose of azithromycin was offered to all residents of
      both intervention and control balozi after the baseline survey. Households (and
      surrounding areas) in the intervention group were then sprayed with insecticide
      throughout the ensuing year and monitored for reductions in fly counts. This
      study is registered at ClinicalTrials.gov, number NCT00347763. FINDINGS: The
      intervention balozi had significantly lower fly counts than controls at all
      monitored weeks (p<0.05), apart from weeks 7-9. The trachoma rate did not differ
      significantly in the intervention and control balozi at 6 months post-treatment
      (20%vs 33%, p=0.07), nor did it at 1 year (43%vs 44%, p=0.90). Infection with C
      trachomatis did not differ between groups at 6 months post-treatment (9%vs 7%,
      p=0.45). INTERPRETATION: Intensive insecticide spraying reduced flies in the
      environment, but our results suggest that fly reduction after mass antibiotic
      treatment has no added benefit on reduction of trachoma.

PMID- 16905027
TI  - First things first.

PMID- 16905026
TI  - Is there a role for recombinant insulin-like growth factor-I in the treatment of
      idiopathic short stature?

PMID- 16905028
TI  - Bilateral cataracts and glaucoma induced by long-term use of oral prednisolone
      bought over the internet.

PMID- 16905029
TI  - Colorectal cancer testing among patients cared for by Iowa family physicians.
AB  - BACKGROUND: Colorectal cancer (CRC) can be largely prevented or effectively
      treated, yet about half of eligible Americans have not been screened. The purpose
      of this study was to examine patient and physician factors associated with
      documented CRC testing according to national guidelines. METHODS: Cross-sectional
      study where 511 randomly selected rural patients aged 55 to 80 years of 16 board
      certified Iowa family physicians were enrolled in 2004. Patient survey and
      medical record information were linked with physician surveys. Predictors of CRC
      testing were examined using a regression procedure that accommodated random
      physician effects (2005-2006). RESULTS: Forty-six percent of patients were up-to
      date with CRC testing in accordance with national guidelines. This percentage
      varied from 5% to 75% by physician (p < 0.0001). Of the patients who were up-to
      date, 89% had colonoscopy, and 62% had symptoms prior to testing that could
      indicate CRC. The strongest univariate predictors other than symptoms were
      patient recollection of physician recommendation (odds ratio [OR] = 6.4, 95%
      confidence interval [CI] = 4.2-9.6) and physician documentation of recommendation
      (OR = 14.1, CI = 8.5-23.3). A multivariable regression model showed testing in
      accordance with guidelines significantly increased with government insurance (OR
      = 1.6, CI = 1.2-2.3), having a health maintenance visit in the preceding 26
      months (OR = 2.4, CI = 1.4-4.1), family history of CRC (OR = 3.1, CI = 1.6-5.8),
      number of medical conditions (OR = 1.2 for each additional condition, CI = 1.1
      1.3), high importance of screening to patient (OR = 2.6, CI = 1.5-4.5), patient
      satisfaction with doctor's discussions (OR = 3.3, CI = 2.2-4.8), physician
      trained in flexible sigmoidoscopy (OR = 2.3, CI = 1.6-3.4), and physician report
      of trying to follow American Cancer Society (ACS) guidelines (OR = 1.7, CI = 1.2
      2.5). After excluding patients who had symptoms prior to screening, most of the
      ORs in the logistic regression analysis increased except that the number of
      medical conditions and physician trying to follow ACS guidelines became
      nonsignificant. CONCLUSIONS: Fewer than half of rural patients received CRC
      testing, and most of those tested had symptoms. Physician recommendations and the
      manner of presenting the recommendations greatly influenced whether patients were
      tested.

PMID- 16905030
TI  - Patient-physician colorectal cancer screening discussions and screening use.
AB  - BACKGROUND: Little is known about patient-physician colorectal cancer (CRC)
      screening discussions or how discussion content affects screening use. Analyses
      conducted in 2004-2005 of patient-physician CRC screening discussion content and
      its association with screening use are described. METHODS: A mailed survey and
      retrospective claims data were used to compile information on insured, primary
      care patients aged 50 to 70 years (n = 4966). The survey collected information on
      patient-physician CRC screening discussion content (including the 5A's: assess,
      advise, agree, assist, and arrange). Survey responses were linked with 5-year
      retrospective claims data (ending December 31, 2003) on CRC screening use. Among
      patients reporting screening discussions, generalized estimating equation
      approaches were used to estimate the association of discussion content with
      screening use. RESULTS: Among those reporting discussion information (n = 2463),
      80% reported discussing CRC screening with their physician. The content of these
      discussions varied, and only 54% used CRC screening. Multivariable model results
      indicated that the likelihood of screening was greater among patients reporting
      help scheduling an appointment (assist) (odds ratio [OR] = 2.69, 95% confidence
      interval [CI] = 1.95-3.72) and those reporting a discussion of results or follow
      up (arrange) (OR = 1.63, 95% CI = 1.18-2.24), and lower among patients offered a
      choice among screening modalities (agree) (OR = 0.57, 95% CI = 0.37-0.86) as well
      as among those who wanted more screening information (OR = 0.65, 95% CI = 0.43
      0.97). CONCLUSIONS: Not all patient-physician CRC screening discussions result in
      CRC screening use. It is important to understand which aspects of shared decision
      making and discussion content are likely to increase informed and value
      concordant decisions to participate in recommended evidence-based CRC screening.

PMID- 16905031
TI  - Active transportation increases adherence to activity recommendations.
AB  - BACKGROUND: Levels of physical activity (PA) contribute to health status and
      outcomes directly and indirectly via the effects of PA on obesity and other risk
      factors. Much past surveillance has focused on leisure-time physical activity
      (LTPA), but this may bias estimates of prevalence. This study explores inclusion
      of non-leisure-time walking and bicycling (NLTWB) used for transportation on the
      prevalence of adherence to PA recommendations and the magnitude of apparent
      disparities in adherence for California adults. METHODS: Results of the 2001
      California Health Interview Survey, a large (n = 55,151) telephone survey were
      analyzed in 2005 using tabulation and logistic regression. RESULTS: Higher levels
      of LTPA were associated with youth, males, education, income, Pacific Islanders,
      and non-Hispanic (NH) whites. Inclusion of NLTWB reduced these differences for
      all five variables. The largest decreases in disparities in adherence occurred
      for race/ethnicity, education, and income, with decreases in adherence
      differences from approximately 18% to 7% for NH white vs Latino, approximately
      27% to 16% for more than high school versus less than high school, and
      approximately 25% to 11% for more than 300% versus less than 100% of poverty
      level. Logistic regression comparing adherence gives similar results. For
      example, in respondents with more than high school education versus less than
      high school education (referent), the odds ratio changed from 2.23 (95%
      confidence interval [CI] = 2.0-2.4) to 1.7 (1.6-1.9) after the inclusion of
      NLTWB. CONCLUSIONS: Assessment of PA in multiple domains is required to
      understand differences in total levels of PA for people with different incomes,
      education levels, and racial/ethnic backgrounds. Inclusion of NLTWB reduces but
      does not eliminate disparities in adherence to recommended levels of PA.

PMID- 16905035
TI  - Ice cream illusions bowls, spoons, and self-served portion sizes.
AB  - BACKGROUND: Because people eat most of what they serve themselves, any contextual
      cues that lead them to over-serve should lead them to over-eat. In building on
      the size-contrast illusion, this research examines whether the size of a bowl or
      serving spoon unknowingly biases how much a person serves and eats. METHODS: The
      2 x 2 between-subjects design involved 85 nutrition experts who were attending an
      ice cream social to celebrate the success of a colleague in 2002. They were
      randomly given either a smaller (17 oz) or a larger (34 oz) bowl and either a
      smaller (2 oz) or larger (3 oz) ice cream scoop. After serving themselves, they
      completed a brief survey as their ice cream was weighed. The analysis was
      conducted in 2003. RESULTS: Even when nutrition experts were given a larger bowl,
      they served themselves 31.0% more (6.25 vs 4.77 oz, F(1, 80) = 8.05, p < 0.01)
      without being aware of it. Their servings increased by 14.5% when they were given
      a larger serving spoon (5.77 vs 5.04 oz, F(1, 80)=2.70, p = 0.10). CONCLUSIONS:
      People could try using the size of their bowls and possibly serving spoons to
      help them better control how much they consume. Those interested in losing weight
      should use smaller bowls and spoons, while those needing to gain weight--such as
      the undernourished or aged--could be encouraged to use larger ones. Epidemiologic
      implications are discussed.

PMID- 16905034
TI  - Smoking cessation treatment by primary care physicians: An update and call for
      training.
AB  - BACKGROUND: Public health and government organizations have invested considerably
      to increase physician adherence to smoking-cessation practice guidelines.
      METHODS: A random sample of 2000 U.S. primary care physicians was ascertained
      from the American Medical Association (AMA) in 2002. Respondents (n = 1120,
      62.3%) provided self-reported data about individual and practice characteristics
      and smoking-cessation practices. Data were analyzed in 2005. RESULTS: Most
      primary care physicians (75%) advised cessation, 64% recommended nicotine
      patches, 67% recommended bupropion, 32% recommended nicotine gum, 10% referred to
      cessation experts, and 26% referred to cessation programs "often or always."
      Advising cessation was related to being older, having a faculty appointment,
      having trained staff for smoking counseling, and having confidence to counsel
      patients about smoking. Physicians who were internists, younger, and those with
      greater confidence to counsel patients about smoking recommended nicotine
      replacement more often. Prescribing bupropion was less common among older
      physicians, in the Northeast, with trained staff available for counseling, and
      with a greater proportion of minority or Medicaid patients. Prescribing bupropion
      was more common among AMA-member physicians and physicians with greater
      confidence to counsel patients about smoking. Providing a referral to an outside
      expert or program was more common among female physicians, and physicians in the
      Northeast or West, with larger clinical practices, and with trained staff for
      cessation counseling. CONCLUSIONS: Current physician self-reported practices for
      smoking cessation suggest opportunity for improvement. Targeted efforts to
      educate and support subsets of primary care physicians may improve physician
      adherence and smoking outcomes.

PMID- 16905033
TI  - Tobacco denormalization and industry beliefs among smokers from four countries.
AB  - BACKGROUND: Tobacco denormalization is an important concept for understanding
      smoking behavior. The present study sought to assess beliefs about the tobacco
      industry and the social acceptability of smoking among nationally representative
      samples of adult smokers from four countries, and to assess the relationship of
      these measures to cessation behavior and tobacco-control policy. DESIGN: A
      longitudinal survey of 9058 adult smokers from Canada (n = 2214), the United
      States (n = 2138), the United Kingdom (n = 2401), and Australia (n = 2305), was
      conducted in October-December 2002 and again in June and August 2003 (75% follow
      up rate). The analyses were conducted in 2005. RESULTS: The findings indicate
      that few smokers perceive approval for their smoking, and most hold relatively
      antagonistic beliefs toward the tobacco industry. For example, 80% of smokers
      reported that society disapproves of smoking, and more than three quarters
      reported that tobacco companies cannot be trusted to tell the truth. Social and
      industry denormalization were independently associated with intentions to quit
      smoking. Baseline levels of social denormalization were associated with
      abstinence at the 8-month follow-up, as were changes in industry denormalization
      beliefs between baseline and follow-up. Anti-industry beliefs at baseline did not
      predict abstinence at follow-up. A similar pattern of findings was observed
      across all four countries. In addition, social denormalization and anti-industry
      beliefs were significantly associated with tobacco-control policies, such as
      noticing health warnings on packages and greater workplace smoking restrictions.
      CONCLUSIONS: Tobacco denormalization constructs were independently linked to
      cessation-related outcomes among adults from four countries. Tobacco-industry
      denormalization themes in mass media campaigns may help to reduce tobacco use
      above and beyond more traditional communications that target social norms.

PMID- 16905032
TI  - Midlife physical activity and mobility in older age: The InCHIANTI study.
AB  - BACKGROUND: Among older adults, loss of mobility represents a critical stage in
      the disablement process, whereby the risk for disability is significantly
      increased. Physical activity is a modifiable risk factor that is associated with
      reduced risk of losing mobility in older adulthood; however, few studies have
      examined physical activity performed earlier in life in relation to mobility
      later in life. METHODS: Data from a population-based study of 1155 adults aged 65
      years and older living in the Chianti region of Italy in 1998-2000 were analyzed
      in 2005 and 2006. Participants retrospectively recalled their physical activity
      levels in midlife and underwent mobility testing and medical examination. Two
      objective mobility outcomes were examined as a function of past physical
      activity: the Short Physical Performance Battery (SPPB) and the ability to walk
      400 meters. RESULTS: Older Italian adults (mean age 74.8, standard deviation 7.3)
      who engaged in higher levels of physical activity in midlife were significantly
      more likely to perform better on the SPPB than individuals who were less
      physically active in midlife. In addition, failure to complete the 400-meter walk
      test was significantly less likely among physically active men (Level II) (odds
      ratio [OR] = 0.37, 95% confidence interval [CI] = 0.15-0.93) and very active men
      (Level III) (OR = 0.23, 95% CI = 0.09-0.63) when compared to men who were less
      active (Level I) in the past (p for trend, 0.008). These associations remained
      after adjustment for demographic factors, medical conditions, and physiologic
      impairments. CONCLUSIONS: Older adults who reported higher levels of physical
      activity in midlife had better mobility in old age than less physically active
      ones.

PMID- 16905037
TI  - Cases and deaths during influenza pandemics in the United States.
AB  - OBJECTIVE: To assess how numbers and age distributions of cases and deaths during
      an influenza pandemic in the United States would potentially vary from those
      during the 1918-1919 pandemic, given the same virulence of the pandemic strain.
      METHODS: Influenza cases and deaths in two referent populations (U.S. residents
      in 1917 and 2006) were calculated using clinical case rates from three pandemics
      (1918-like, 1957-like, and 1968-like) and case fatality rates from the 1918-1919
      pandemic. RESULTS: Across pandemic scenarios, overall case ("attack") rates
      ranged from 24.7% to 34.2%, and overall death rates ranged from 4.4 to 6.7 per
      1000. In both referent populations, total cases and deaths were significantly
      higher when using 1957-like and 1968-like, compared to 1918-like, case rates.
      Under all pandemic scenarios, the most deaths occurred among those aged 25 to 29
      years. However, in the 2006 referent population, there were large numbers and
      high proportions of deaths in middle-aged and elderly adults (unlike during the
      1918-1919 pandemic). CONCLUSIONS: Numbers and distributions of cases and deaths
      during influenza pandemics depend on numbers of individuals, clinical case rates,
      and case fatality rates in relation to age. During a future pandemic in the
      United States, influenza deaths will likely not be as sharply focused in young
      adults as in 1918-1919 (even if case fatality rates are similar) because of
      larger proportions of middle-aged and elderly adults and potentially higher case
      rates among adults older than 30.

PMID- 16905038
TI  - Trends in smoking among Hispanic women in California: Relationship to English
      language use.
AB  - BACKGROUND: Research has shown that Hispanic women who speak mostly English have
      higher smoking rates than those who speak mostly another language. It is unknown
      how differences in smoking by English language use among adult Hispanic women in
      California have changed in recent years. METHODS: We compared current daily (100
      or more cigarettes in lifetime, now smokes daily) and current nondaily (100 or
      more cigarettes in lifetime, now smokes some days) smoking prevalence for adult
      Hispanic women by English language use at home from population-based, random
      digit-dialed California Tobacco Surveys in 1996 (n = 1406, 74% response rate
      [RR]); 1999 (n = 1379, 69% RR), and 2002 (n = 2912, 64% RR). RESULTS: Current
      smoking prevalence was at least twice as high among those who speak mostly
      English compared to those who speak mostly another language in every survey year
      (1996: 14.7% vs 6.1%; 1999: 14.6% vs 6.1%; 2002: 11.7% vs 4.9%) with the ratio
      staying constant (2.4:1). There was a decline in current nondaily smoking among
      those who speak mostly English by 2002 (1996 and 1999 prevalence: approximately
      6%, 2002: approximately 4%), but no declines in current daily smoking for either
      language-use group. CONCLUSIONS: There has been no reduction in the English
      language-use gap in smoking among Hispanic women in California. There has been a
      significant decline in current nondaily smoking prevalence among women who speak
      mostly English, but no significant reduction in current daily smoking for either
      language-use group. It appears that not much progress has been made in California
      in reducing daily smoking prevalence among Hispanic women at the population
      level. Smoking prevention and cessation efforts among Hispanic women remain a
      priority.

PMID- 16905040
TI  - Paternal relatives and family history of breast cancer.
AB  - BACKGROUND: Reported family medical history may be the most widely accessible
      genomics screen currently available. The worth of any population-screening tool
      may be measured by parameters such as sensitivity and specificity. There is some
      evidence and theory suggesting that family history of breast cancer may be more
      frequently communicated about maternal (versus paternal) lines. If true, a
      discrepancy in reporting family history of breast cancer could mean suboptimal
      accuracy for this genomics-screening tool. METHODS: A cross-sectional analysis of
      reported family history of breast cancer was conducted beginning in early fall
      2005 of data collected from April 2003 to March 2005. Study participants were
      Women's Health Clinic patients without breast cancer aged at least 40 years. The
      number of women reporting extended paternal relatives (e.g., aunts, grandmothers)
      with breast cancer was compared to the number of women reporting maternal
      relatives. RESULTS: More women reported a maternal relative with breast cancer
      (16%) compared to those reporting paternal relatives (10%) (McNemar odds ratio =
      1.71, 95% confidence interval = 1.26 to 2.34). A discrepancy remained in analyses
      adjusting for potential covariates (race/ethnicity, awareness of breast cancer,
      family communication about breast cancer, and perceived risk). CONCLUSIONS: Self
      reported family history of breast cancer may not optimally capture inherited risk
      from the father's side of the family. Further research is needed to look for
      modifiable contributors to this discrepancy to optimize screening for familial
      breast cancer.

PMID- 16905039
TI  - Response to overdose among injection drug users.
AB  - BACKGROUND: Drug overdose is a leading cause of mortality among illicit drug
      users. This study characterizes responses to overdose among injection drug users
      (IDUs) in Baltimore, Maryland, and identifies factors associated with medically
      inappropriate response. METHODS: A cross-sectional survey was administered to 924
      IDUs in an ongoing cohort study between August 2003 and September 2004. Self
      reported experiences of witnessing overdose were obtained by structured
      interview. Multiple logistic regression identified associations between overdose
      information sources and medically inappropriate responses. RESULTS: Most IDUs
      (69.7%) reported ever witnessing an overdose. The most common responses were
      walking the victim around (70.8%), shaking them (64.9%), and inflicting pain
      (62.6%). One in four (25.8%) injected the victim with salt water. Two thirds
      (63.4%) called 911, but more than half delayed the call by 5 or more minutes. The
      most common reason cited for delaying or foregoing the 911 call was the belief
      that they could revive the victim themselves, followed by fear of police
      involvement. Most IDUs had received information on how to prevent or respond to
      an overdose, but most (73.2%) received this information from friends or other
      drug users. IDUs who got overdose information solely from lay sources were less
      likely to call 911 (adjusted odds ratio [AOR] = 0.66, 95% confidence interval
      [CI] = 0.46-0.94) and more likely to inject the victim with salt water (AOR =
      2.06, 95% CI = 1.36-3.13) than IDUs who received no information at all. Injection
      drug users who received information from medical and social services providers
      only were less likely to delay the 911 call (AOR = 0.35, 95% CI = 0.22-0.72).
      CONCLUSIONS: Inappropriate overdose responses are widespread among IDUs in
      Baltimore. Interventions that provide overdose education and reduce police
      response to overdose events may improve witness response and reduce mortality
      associated with drug overdose.

PMID- 16905036
TI  - Parents concerned about vaccine safety: Differences in race/ethnicity and
      attitudes.
AB  - BACKGROUND: Parental concerns about immunization safety have been covered widely
      in the media and on the Internet and have been correlated in some studies with
      under-immunization and the late receipt of immunizations. OBJECTIVES: Phase 1: To
      (1) measure the prevalence of parents with immunization safety concern,
      specifically those with high-level concern, (2) determine demographic
      characteristics and attitudes typical for this subgroup of parents, and (3)
      determine factors that influence such parents, nevertheless, to have their
      children immunized. Phase 2: To further explore the racial/ethnic difference
      found in the first-phase results, specifically to compare the immunization
      attitudes of Hispanic (both black and white) and non-Hispanic black parents with
      those of non-Hispanic white parents. METHODS: ConsumerStyles (2004) survey data
      of a nationwide panel of U.S. adults were analyzed in January 2006. In Phase 1,
      bivariate and logistic regression analyses were used to identify factors
      associated with parental concerns about immunization safety. In Phase 2, logistic
      regression was used to compare immunization attitudes among non-Hispanic black;
      Hispanic (both black and white); and non-Hispanic white parents. RESULTS: The
      response rate was 62% (6207/10,000); analysis was restricted to the 2937 (47%)
      respondents who were parents with a child aged 18 years or younger; 634 (21%)
      responded with the highest level of concern, 5 on a 1-to-5-point scale.
      Demographics (Hispanic ethnicity/nonwhite race, low income, and less education)
      and negative attitudes toward immunization and the child's healthcare provider
      were significantly associated with high-level concern. Seventy-two percent of
      parents with high-level concern responded that the risk of a child getting a
      disease was their primary reason for having their child immunized, while 17%
      listed state laws requiring immunizations for school/daycare entry. Importantly,
      black parents were more likely than white parents to have negative attitudes
      toward immunizations and their child's healthcare provider. CONCLUSIONS: One
      fifth of parents reported high-level concern with the safety of childhood
      immunizations. To prevent the erosion of childhood immunization rates, healthcare
      providers need to learn how to recognize and address these concerns.

PMID- 16905041
TI  - Promoting smoking cessation in the healthcare environment: 10 years later.

PMID- 16905046
TI  - Allergic reactions to acrylics.

PMID- 16905047
TI  - History of orthodontics.

PMID- 16905042
TI  - Low risks at high latitudes: Does the arctic hold clues to prostate cancer?

PMID- 16905049
TI  - Staff training.

PMID- 16905052
TI  - Accessing evidence via the Internet.

PMID- 16905051
TI  - History of functional appliances.

PMID- 16905053
TI  - A practical method for determining pubertal growth spurt.
AB  - INTRODUCTION: It is important to evaluate skeletal maturation in orthodontic
      treatment. Hand-wrist and cervical maturation stages have been shown to be
      correlated with skeletal growth changes during puberty. The cervical vertebrae
      have 6 maturation phases, whereas the medial phalange of the third finger has 5
      stages; a modified version has 6 stages. The purpose of this study was to
      determine the correlation of the cervical vertebrae maturation index with the
      modified medial phalange index. METHODS: Lateral cephalometric and left-hand
      medial phalange radiographs of 150 males between the ages of 9 and 19 who were
      referred for orthodontic treatment were examined. RESULTS: The 6 modified medial
      phalange stages were found to correlate with the 6 cervical vertebral maturation
      stages. CONCLUSIONS: Because cervical vertebrae stage is a reliable maturation
      indicator, the medial phalange of the third finger can be used instead to assess
      a subject's skeletal maturation.

PMID- 16905054
TI  - The relationship between craniofacial structures and the nose in Anatolian
      Turkish adults: a cephalometric evaluation.
AB  - INTRODUCTION: The aim of this study was to evaluate the relationship between the
      facial skeletal and the nasal profile in Anatolian Turkish adults. This
      prospective study was conducted at Gazi University, Faculties of Dentistry and
      Medicine, in Ankara, Turkey. METHODS: The sample included 262 Turkish adults (167
      women, 95 men), aged 18 to 30 years. Fifteen facial skeletal parameters and 12
      nasal parameters (10 soft tissue and 2 nasal skeletal) were measured on lateral
      cephalograms. Analysis of variance, Duncan test, and Pearson correlation analysis
      were used for statistical analysis. RESULTS: The anteroposterior and vertical
      classifications were found to be significant with analysis of variance in certain
      parameters such as nasolabial angle (P < .05), nasomental angle (P < .001), and
      soft-tissue facial convexity (P < .001). Sex was also found to be significant for
      nasal length (P < .001), nasal depths (P < .05, P < .001), and hump (P < .01), in
      addition to soft-tissue facial convexity (P < .01). The results also showed
      correlations between the skeletal and nasal parameters. Facial heights, lengths,
      and the anteroposterior/vertical position of the maxilla and mandible were found
      to be correlated to nasal length and form. CONCLUSIONS: Nasal length, prominence,
      and form are associated with height and length of the maxilla and the mandible.
      Posterior-inferior development of the face results in a convex nasal profile,
      whereas anterior development produces a straight or concave nasal profile.

PMID- 16905050
TI  - An open letter to the ABO: righting past wrongs.

PMID- 16905055
TI  - Qualitative and quantitative evaluation of enamel after various stripping
      methods.
AB  - INTRODUCTION: In this study, we investigated ultramorphology, surface roughness,
      and microhardness of permanent and deciduous tooth enamel after various stripping
      methods. METHODS: One hundred twenty deciduous and permanent teeth (n = 60 each)
      were used. Qualitative (scanning electron microscopy) and quantitative (surface
      roughness and microhardness tests) experiments were carried out in the following
      experimental groups: group 1, stripping disk; group 2, diamond-coated metal
      strip; group 3, stripping disk and Sof-Lex discs (3M-ESPE, Seefeld, Germany);
      group 4, diamond-coated metal strip and Sof-Lex discs; group 5 (chemical
      stripping), 37% orthophosphoric acid in conjunction with diamond-coated metal
      strip; group 6 (control), no stripping. Surface roughness values (Ra) for
      permanent and deciduous enamel were evaluated with Welch analysis of variance
      (ANOVA) and Tamhane tests, and Kruskal-Wallis and Mann-Whitney tests,
      respectively. Microhardness values were evaluated statistically with Kruskal
      Wallis, 1-way ANOVA, and Duncan tests. RESULTS: Deciduous and permanent teeth
      showed similar results in terms of surface roughness and surface morphology.
      Groups 3 and 4 had the smoothest deciduous and permanent enamel surfaces, whereas
      chemical stripping (group 5) produced the roughest surfaces in both enamel types.
      Stripping did not lead to a significant change in the microhardness of permanent
      enamel. CONCLUSIONS: All stripping methods significantly roughened the enamel
      surfaces. Polishing the stripped surface with Sof-Lex discs decreased the
      roughness.

PMID- 16905056
TI  - ABO certification in the age of evidence and enhancement.
AB  - The American Board of Orthodontics (ABO) phase III certification examination was
      originally constructed and recently modified to "help the Board determine the
      candidate's knowledge of clinical orthodontics and provide a basis to assess the
      quality of the candidate's clinical treatment results." For the most part, the
      ABO phase III examination measures the orthodontic treatment-induced changes in
      occlusion in a limited and biased patient sample. The process and outcome
      measures used in the current model-the discrepancy index and the objective
      grading system-are so narrowly focused that an orthodontist might lack up-to-date
      clinical knowledge, psychomotor and critical thinking skills, diagnostic acumen,
      patient management ability, and patient-centered ethics, and still pass the
      examination largely because of mechanically morphing the patient's teeth into the
      board's construct of ideal occlusion. The goal of this article is to provide
      provocative insight into the core concepts that drive the ABO phase III
      certification process and to recommend an alternative paradigm predicated on a
      patient-centered, evidence-based clinical practice model.

PMID- 16905057
TI  - Perceptions of dental professionals and laypersons to altered dental esthetics:
      asymmetric and symmetric situations.
AB  - INTRODUCTION: Previous studies evaluated the perception of laypersons to
      symmetric alteration of anterior dental esthetics. However, no studies have
      evaluated the perception of asymmetric esthetic alterations. This investigation
      will determine whether asymmetric and symmetric anterior dental discrepancies are
      detectable by dental professionals and laypersons. METHODS: Seven images of
      women's smiles were intentionally altered with a software-imaging program. The
      alterations involved crown length, crown width, midline diastema, papilla height,
      and gingiva-to-lip relationship of the maxillary anterior teeth. These altered
      images were rated by groups of general dentists, orthodontists, and laypersons
      using a visual analog scale. Statistical analysis of the responses resulted in
      the establishment of threshold levels of attractiveness for each group. RESULTS:
      Orthodontists were more critical than dentists and laypeople when evaluating
      asymmetric crown length discrepancies. All 3 groups could identify a unilateral
      crown width discrepancy of 2.0 mm. A small midline diastema was not rated as
      unattractive by any group. Unilateral reduction of papillary height was generally
      rated less attractive than bilateral alteration. Orthodontists and laypeople
      rated a 3-mm distance from gingiva to lip as unattractive. CONCLUSIONS:
      Asymmetric alterations make teeth more unattractive to not only dental
      professionals but also the lay public.

PMID- 16905058
TI  - Influence of lips on the perception of malocclusion.
AB  - INTRODUCTION: The purpose of the study was to determine the influence of
      variations in the size of the vermilion borders of the upper and lower lips on
      the perception of the attractiveness of various occlusal traits. METHODS: Ten
      occlusal traits and 3 upper and 3 lower vermilion variations, placed in
      combinations on a facial image, were used in a questionnaire. Statistical
      analyses for attractiveness and social and sex attributes were performed for
      various occupational groups. RESULTS: The occlusion, vermilion border of the
      upper and lower lips separately, and the raters' occupations were all highly
      significant in influencing attractiveness, social perceptions, and perceived sex
      of the images (P < .01). All occlusal traits were perceived as more attractive
      with a thicker vermilion border. Thin vermilion borders and more severe
      irregularity were associated with unattractiveness, aggressiveness, and masculine
      traits. CONCLUSIONS: This study demonstrates that the thickness of the vermilion
      border has a profound effect on how people rate the attractiveness of the
      dentition. Therefore, treatment plans that could affect lip vermilion might
      result in improved dental alignment but also deterioration in overall
      attractiveness. Orthodontists placed more emphasis on the teeth than other
      occupation groups; this demonstrated an occupational bias.

PMID- 16905059
TI  - Peer assessment of dental attractiveness.
AB  - INTRODUCTION: The objectives of the study were to determine the relative
      importance of various dental features that contribute to overall dental
      attractiveness and to test the validity of the concepts of golden proportion and
      golden percentage as applied to the human dentition. METHODS: Sixty 30-year-old
      subjects (29 men, 31 women) were selected from the 20-year longitudinal Cardiff
      Survey. Color photographs of the subjects' dentitions were taken with the lips
      retracted so that their teeth and gums were clearly exposed. Twelve nondentists,
      aged 32 to 33 years, equally divided according to sex, rated the subjects' dental
      appearances on a 5-point Likert attractiveness scale. The maxillary anterior
      teeth were measured, and relevant ratios were calculated and compared with the
      golden proportion. Factor analyses and linear regression were used to investigate
      the hierarchy of dental features, and variance components analysis was used to
      estimate interrater agreement. RESULTS AND CONCLUSIONS: Overall dental
      attractiveness did not depend on any particular feature of the dentition. A
      hierarchy of various features was established, with crown shape ranked highest,
      and tooth and gum color ranked lowest. The golden proportion and the golden
      percentage were not decisive factors in determining dental attractiveness.

PMID- 16905060
TI  - Perceptions of dental esthetics of Asian orthodontists and laypersons.
AB  - INTRODUCTION: The aim of the study was to determine the impact of anterior dental
      crowding, overjet, overbite, dental spacing, and type of malocclusion on dental
      esthetic perceptions of Asian orthodontists. METHODS: Twenty-one Asian
      orthodontists (10 men, 11 women) and 158 adult laypersons (38 men, 120 women)
      rated the attractiveness of 50 pairs of black-and-white intraoral photographic
      prints of various types of malocclusions. Each pair included a frontal and a
      right buccal view of the dentition at maximum intercuspation. Raters used a
      visual analogue scale (VAS), with "least attractive" (0 mm) and "most attractive"
      (100 mm) as the 2 extremes, to score the dental esthetics of the photographs. A
      principal investigator objectively measured the dental traits from study models.
      Linear regression analysis was performed with VAS scores as the dependent
      variable and anterior dental crowding, overjet, and overbite measurements as the
      independent variables. Independent sample t tests were used to determine the
      effect of dental spacing on the VAS scores. The Kruskal-Wallis test was used to
      determine the effect of type of malocclusion (Class I, Class II Division 1, Class
      II Division 2, Class III) on VAS scores. RESULTS: Increased overjet (>6 mm) and
      severe maxillary dental crowding (>8 mm) were found to be significantly
      correlated with laypersons' VAS scores (P <.05). Reverse overjet was found to be
      significantly correlated with orthodontists' VAS scores (P <.05). No significant
      correlation was found between overbite, dental spacing, and VAS scores. Class III
      malocclusions were significantly perceived to be the most unesthetic by
      orthodontists. CONCLUSIONS: Overjet was the major occlusal trait that influenced
      the perceptions of dental esthetics of both laypersons and orthodontists.

PMID- 16905061
TI  - Soft-tissue and cortical-bone thickness at orthodontic implant sites.
AB  - INTRODUCTION: To obtain sufficient stability of implants, the thickness of the
      soft tissue and the cortical bone in the placement site must be considered.
      However, the literature contains few anatomical studies of orthodontic implants.
      METHODS: To measure soft-tissue and cortical-bone thicknesses, maxillae from 23
      Korean cadavers were decalcified, and buccopalatal cross-sectional specimens were
      obtained. These specimens were made at 3 maxillary midpalatal suture areas: the
      interdental area between the first and second premolars (group 1), the
      interdental area between the second premolar and the first molar (group 2), and
      the interdental area between the first and second molars (group 3). RESULTS: In
      all groups, buccal soft tissues were thickest closest to and farthest from the
      cementoenamel junction (CEJ) and thinnest in the middle. Palatal soft-tissue
      thickness increased gradually from the CEJ toward the apical region in all
      groups. Buccal cortical-bone was thickest closest to and farthest from the CEJ
      and thinnest in the middle in groups 1 and 2. Palatal cortical-bone thickness was
      greatest 6 mm apical to the CEJ in groups 1 and 3, and 2 mm apical to the CEJ in
      group 2. Along the midpalatal suture, palatal mucosa remained uniformly 1 mm
      thick posterior to the incisive papilla. CONCLUSIONS: Surgical placement of
      miniscrew implants for orthodontic anchorage in the maxillary molar region
      requires consideration of the placement site and angle based on anatomical
      characteristics.

PMID- 16905062
TI  - Cephalometric changes in overbite and vertical facial height after removal of 4
      first molars or first premolars.
AB  - INTRODUCTION: The objective of this study was to evaluate the outcome of standard
      edgewise orthodontic treatment with extraction of 4 first molars (6xT group) or
      Tweed edgewise treatment with extraction of 4 first premolars (4xT group).
      MATERIALS AND METHODS: A cephalometric analysis that isolated tipping and bodily
      tooth movements of the maxillary and mandibular incisors and measured vertical
      skeletal changes in the anterior region of the maxilla and mandible was used.
      Thirty subjects treated by 10 practitioners comprised the 6xT group, whereas 31
      subjects treated in the Case Western Reserve University orthodontic clinic were
      used in the 4xT group. Control groups (6xC and 4xC) were selected from untreated
      subjects enrolled in the Bolton-Brush Growth Study and were matched on age and
      gender. Data were collected before (T1) and after (T2) treatment. RESULTS:
      Analysis of the data showed no statistically significant changes between 6xT and
      6xC for any of the variables studied. An increase in overbite of 2.1 mm in the
      6xT group was the result of small but clinically significant changes in both
      tipping and extrusion of maxillary and mandibular incisors. In the 4xT group,
      statistically and clinically significant changes were observed for intrusion of
      the maxillary and mandibular incisors, resulting in a 4.1-mm decrease in
      overbite. Importantly, both the 6xT and the 4xT groups showed no increase in
      mandibular vertical height during treatment. CONCLUSION: Both treatment
      strategies showed good control of vertical mandibular growth. Bodily intrusion of
      anterior teeth was the main contributor to correction of deep overbite in the
      Tweed edgewise sample.

PMID- 16905064
TI  - Assessment of anterior face height in a native African sample.
AB  - INTRODUCTION: The purpose of this research was to evaluate the anterior face
      height (AFH) of a native African ethnic group. METHODS: Cephalograms of 101 adult
      ethnic Shona subjects (51 men, 50 women; age range, 18 to 38 years) were
      evaluated and compared with norms of African Americans and North American whites.
      A number of measurements, some conventionally used and others specifically
      derived for this study, were assessed, including ANS to Me, Me to PP, and Me to
      FH, TAFH, NOrb, NANS, NPP, OrbANS, and OrbPP. Three age groups were considered:
      less than 22 years, 22 to 25, and more than 25 years. RESULTS: ANOVA detected
      significant differences among the 3 age groups and between the sexes. AFH was
      higher in men than in women. The post hoc Bonferroni test showed that NPP, NANS,
      and OrbPP were significantly different at ages less than 22 and more than 25. The
      older age group had shorter heights than the younger group. The AFH of the Shona
      was significantly lower than that of the African Americans. All AFHs for the men
      and only TAFH for the women were significantly shorter for the Shona than for the
      whites. CONCLUSIONS: The anterior vertical dimension of the Shona subjects was
      anatomically shorter than that of whites and African Americans, and conventional
      measurements did not provide the true status of the Shona, who had shorter lower
      AFHs.

PMID- 16905063
TI  - Alignment stability in Class II malocclusion treated with 2- and 4-premolar
      extraction protocols.
AB  - INTRODUCTION: The purpose of this study was to compare the postretention
      stability of the correction of mandibular anterior-tooth irregularity in patients
      with Class II malocclusions whose orthodontic treatments included extraction of 2
      or 4 premolars. METHODS: A total of 66 patients were selected who initially had
      at least one-half-cusp Class II malocclusions. Nineteen patients (9 male, 10
      female) with an initial mean age of 14.04 years were treated with extraction of 2
      premolars (group 1); 47 patients (20 male, 27 female) with an initial mean age of
      13.03 years were treated with extraction of 4 premolars (group 2). A subgroup of
      group 2, with a similar amount of initial anterior-tooth irregularity as group 1,
      was also compared with group 1. Little's irregularity index was used to evaluate
      anterior tooth irregularity in dental casts obtained from each patient before
      treatment, after treatment, and 5 years after active treatment. Initial
      cephalometric variables, initial treatment priority index, pretreatment age,
      treatment time, and posttreatment time of the groups were compared with t tests.
      Similarly, Little's irregularity index values at prettreament, posttreatment, and
      postretention were also compared with the t test. Cephalometric treatment changes
      within groups were evaluated with dependent t tests. RESULTS: There were no
      statistically significant differences in posttretention anterior-tooth
      irregularity between groups 1 and 2 or the subgroup. CONCLUSIONS: Treatment of
      Class II malocclusion with extraction of either 2 maxillary premolars or 4
      premolars provides the same mandibular anterior-tooth alignment stability.

PMID- 16905065
TI  - A long-term evaluation of the mandibular Schwarz appliance and the acrylic splint
      expander in early mixed dentition patients.
AB  - INTRODUCTION: The aim of this prospective longitudinal clinical study was to
      evaluate the short-term and long-term changes in dental-arch dimensions in
      patients treated with either an acrylic splint rapid maxillary expander alone
      (RME-only) or a rapid maxillary expander combined with a mandibular removable
      Schwarz plate (RME-Sz) in the early mixed dentition, followed later by fixed
      appliances in the permanent dentition. METHODS: The dental casts of 27 RME-only
      patients were compared with those of 23 RME-Sz patients and 16 untreated controls
      (CTRL) with constricted maxillary arches at 4 times: pretreatment (T1), after
      expansion but before fixed appliance therapy (T2), after fixed appliance therapy
      (T3), and at long-term observation (T4). The mean ages for the treated groups
      were approximately 9 years at T1, 12 years at T2, 14 years at T3, and 20 years at
      T4. Arch width, arch depth, arch perimeter, and molar angulation were assessed in
      all subjects at all observation times. T1-T2, T2-T3, T3-T4, and T1-T4 changes
      were compared statistically in the treated groups with respect to the CTRL.
      RESULTS: Treatment with an RME-only or an RME-Sz followed by fixed appliances
      produced significant short-term and long-term increases in maxillary arch widths
      compared with the CTRL. The RME-Sz led to significantly more favorable results
      than the RME-only protocol: (1) significantly greater increases in the transverse
      width of the mandibular arch and mandibular arch perimeter in the long term, and
      (2) uprighting of the mandibular posterior teeth buccally, thus allowing for an
      amount of maxillary expansion that was clinically effective for the correction of
      moderate tooth size-arch size discrepancies. In the overall observation interval,
      the significant increases in maxillary and mandibular arch perimeters in the RME
      Sz group were 3.8 and 3.7 mm, respectively, when compared with the CTRL. The RME
      only protocol produced modest long-term increases in maxillary arch perimeter
      (2.6 mm); the average long-term increase in mandibular arch perimeter (2.0 mm) in
      the RME-only group was not statistically significant. CONCLUSIONS: The RME-Sz led
      to significantly more favorable results than the RME-only protocol.

PMID- 16905066
TI  - Search and selection methodology of systematic reviews in orthodontics (2000
      2004).
AB  - INTRODUCTION: More systematic reviews related to orthodontic topics are published
      each year, although little has been done to evaluate their search and selection
      methodologies. METHODS: Systematic reviews related to orthodontics published
      between January 1, 2000, and December 31, 2004, were searched for their use of
      multiple electronic databases and secondary searches. The search and selection
      methods of identified systematic reviews were evaluated against the Cochrane
      Handbook's guidelines. RESULTS: Sixteen orthodontic systematic reviews were
      identified in this period. The percentage of reviews documenting and using each
      criterion of article searching has changed over the last 5 years, with no
      recognizable directional trend. On average, most systematic reviews documented
      their electronic search terms (88%) and inclusion-exclusion criteria (100%), and
      used secondary searching (75%). Many still failed to search more than MEDLINE
      (56%), failed to document the database names and search dates (37%), failed to
      document the search strategy (62%), did not use several reviewers for selecting
      studies (75%), and did not include all languages (81%). CONCLUSIONS: The
      methodology of systematic reviews in orthodontics is still limited, with key
      methodological components frequently absent or not appropriately described.

PMID- 16905067
TI  - Restricting facial bone growth with skeletal fixation: a preliminary study.
AB  - INTRODUCTION: Conventional orthodontic treatment of vertical or anterior
      maxillary excess by growth modification can be problematic in children because of
      the high levels of patient compliance required. The purpose of this preliminary
      study was to investigate the use of rigid skeletal fixation to modify facial bone
      growth without compliance. METHODS: Three 30-day old female pigs from the same
      litter were included in phase I. Pediatric miniplates were rigidly fixated with
      monocortical screws in the experimental pig to bridge the zygomaticomaxillary
      suture and both the frontonasal and nasomaxillary sutures, bilaterally. In the
      sham experimental pig, the same surgical protocol was followed, but miniplates
      were omitted (ie, screw placement only). In the control pig, surgery was not
      performed. All 3 pigs were housed and fed a normal diet under identical
      conditions postoperatively for 63 days; then they were killed, their right hemi
      skulls were prepared for and underwent 3-dimensional coordinate landmark
      analysis, and en-bloc specimens from the zygomaticomaxillary, frontonasal, and
      nasomaxillary sutures of the left hemi-skulls underwent histologic analysis. Two
      50-day-old female pigs from the same litter were used in phase II. The same
      experimental protocol was followed as before for the experimental pig and the
      sham experimental pig. Both pigs were fed a normal diet for 105 days; then they
      were killed, and their skulls were prepared for and underwent 3-dimensional
      coordinate landmark analysis. RESULTS: Rigid plating restricted
      zygomaticolacrimal suture length, maxillary bone length, nasal bone length,
      midfacial breadth, and frontal bone length by an average of -14% to -15% (range, 
      4% to -36%). No growth differences were noted between the animals in maxillary
      height, mid-premaxillary length, bregma-lambda length, palatal lengths, or
      mandibular length. Also, plating the sutures produced a clear depressed concavity
      in the infraorbital region, altered the alignment of the infraorbital plane
      lateral to the concavity, inhibited the anterior migration of the maxillary
      tuberosity, and resulted in raised folding on the bony surface adjacent to the
      zygomaticomaxillary suture. CONCLUSIONS: Rigidly fixating frontonasomaxillary and
      zygomaticomaxillary sutures inhibits growth of facial bones and might provide a
      means of restricting excess growth without having to rely on patient compliance.
      In addition, these altered growth patterns in the plated pig model produced
      similar and potentially homologous infraorbital features shared by living humans
      in comparison with ancestral fossil forms.

PMID- 16905068
TI  - Effect of various adhesive systems on the shear bond strength of fiber-reinforced
      composite.
AB  - INTRODUCTION: The purpose of this study was to evaluate the effect of 3 adhesive
      systems on the shear bond strength of a fiber-reinforced composite (FRC).
      METHODS: Sixty bovine permanent mandibular incisors were randomly divided into 3
      groups of 20. The FRCs (Ortho, Stick Teck Ltd, Turku, Finland) were bonded to the
      teeth with 3 adhesive systems (Tetric Flow [Ivoclar-Vivadent, Schaan,
      Liechtenstein], Transbond XT [Unitek/3M, Monrovia, Calif], and Fuji Ortho LC [GC
      Europe, Leuven, Belgium]). After bonding, all samples were stored in distilled
      water at room temperature for 24 hours and subsequently tested for shear bond
      strength. Analysis of variance and the Sheffe post-hoc tests were used at a
      significance level of P < .05. RESULTS: ANOVA indicated significant differences
      among the various groups. Fibers bonded with Transbond XT showed significantly
      higher shear bond strengths than the other 2 groups. No significant differences
      in shear bond strength values were reported between Tetric Flow and Fuji Ortho
      LC. No significant differences in debond locations (ARI scores) were found among
      the various groups. CONCLUSIONS: For maximum bond strength, use Transbond XT for
      direct bonding of FRC.

PMID- 16905069
TI  - Mini-implant anchorage for maxillary canine retraction: a pilot study.
AB  - INTRODUCTION: This clinical pilot study evaluated the stability, surrounding soft
      tissue health, and patient comfort and acceptance of a mini-implant used as
      anchorage for maxillary permanent canine retraction. METHODS: The study was
      conducted in the Graduate Orthodontic Clinic of the University of Oklahoma
      College of Dentistry. The sample comprised 16 subjects who had maxillary first
      premolars extracted. In each patient, Ortho Implants (IMTEC, Ardmore, Okla) were
      placed laterally in the maxillary alveolar ridge between the roots of the
      permanent first molars and the second premolars by an oral surgeon. All
      retraction was accomplished on 0.017 x 0.025-in stainless steel archwires in
      0.022-in slots by using nickel-titanium springs stretched from the implant head
      to the brackets on the canines. RESULTS: Placement protocol strongly affected the
      stability of the implants; 1 protocol resulted in the loss of 51% of the implants
      (19 of 39), and the second protocol resulted in 100% stability (10 of 10). The
      surrounding soft tissue remained healthy around stable implants and less healthy
      around implants that were unstable or lost. Patient comfort was excellent in all
      but 1 patient. Rates of canine retraction were calculated monthly and varied
      widely from +6.1 to -1.5 mm per month. Excessive crown tipping into the
      extraction spaces was observed in 4 of the 28 retracted canines and was related
      to the method of ligation of the canine to the archwire. CONCLUSIONS: Ortho
      Implants are adequate anchorage for maxillary canine retraction when properly
      placed.

PMID- 16905073
TI  - Development of imaging selection criteria and procedures should precede
      cephalometric assessment with cone-beam computed tomography.
AB  - Cone-beam computed tomography (CBCT) systems for craniofacial imaging are now
      available from several manufacturers. CBCT potentially provides opportunities for
      3-dimensional cephalometrics in orthodontic assessment of bony landmarks and air
      bounded surfaces such as the facial skin. Two-dimensional cephalogram simulation
      could facilitate the transfer of growth projections from existing data sets as a
      starting point for use of a new 3-dimensional paradigm. Three methods are
      described to simulate conventional 2-dimensional cephalograms from CBCT images
      and volumetric data sets. However, certain precautions are required to assure
      that selection criteria and imaging parameters guarantee a radiation dose that is
      as low as reasonably achievable.

PMID- 16905074
TI  - Litigation, legislation, and ethic. Time marches on.

PMID- 16905072
TI  - Orthodontics in 3 millennia. Chapter 10: midcentury retrospect.
AB  - Late in orthodontics' second millennium, we paused to retrace the path that
      brought us to be practitioners of "the latest and the best" as Angle might have
      put it. What we thought was state of the art proved to be only a stepping stone
      along that path. The best was yet to come.

PMID- 16905071
TI  - Correction of a canted occlusal plane with miniscrews in a patient with facial
      asymmetry.
AB  - The inability of orthodontists to change the cant of the maxillary occlusal plane
      without surgical intervention is a limitation of orthodontic treatment. LeFort I
      osteotomy with asymmetric maxillary impaction is often used to correct this
      problem. However, canting caused by extruded teeth can be corrected easily with
      normal orthodontic appliances and skeletal anchorage. The correction occurs
      through intrusion of the extruded teeth on 1 side of the maxilla, thereby
      avoiding a more aggressive surgical approach. A 22-year-old Korean man with
      facial asymmetry and mandibular prognathism treated in this manner showed the
      possibility of correcting occlusal plane canting with miniscrews.

PMID- 16905075
TI  - How long to postpone an operation after a myocardial infarction? When
      perioperative consultants contradict the literature, leaving the anesthesiologist
      in the middle.

PMID- 16905078
TI  - Dantrolene reconstitution: can warmed diluent make a difference?
AB  - STUDY OBJECTIVE: To evaluate the drug constitution of dantrolene by comparing
      reconstitution with diluent at ambient and warmed temperatures, so as to
      determine whether differences in reconstitution time might provide clinical or
      therapeutic advantages. DESIGN: Randomized study. SETTING: University-affiliated
      medical center. MEASUREMENTS AND MAIN RESULTS: We reconstituted 10 vials of
      dantrolene, 5 with room-temperature diluent (sterile water) and 5 with diluent
      warmed to approximately 41 degrees C. Injection of diluent (10 seconds) was
      followed by 5 seconds of observation and recurring 15-second cycles (10 seconds
      of moderate manual agitation followed by 5 seconds of observation) until full
      reconstitution. In a second series of reconstitutions, warmed diluent injection
      was immediately followed by predetermined lengths of moderate manual agitation,
      and reconstitution status was noted at the end of each trial. Time to full
      reconstitution was based on a series of predetermined objective criteria. In
      experiment 1, with ambient-temperature diluent (22.0 degrees C -23.1 degrees C),
      reconstitution occurred in 90 to 130 seconds; whereas warmed diluent (40.7
      degrees C-41.3 degrees C) reconstitution occurred in less than 30 seconds
      (P<0.004). In experiment 2, with warmed diluent (40.9 degrees C), full
      reconstitution occurred after 10 seconds of injection and 18 seconds of moderate
      manual agitation. CONCLUSION: The use of prewarmed diluent to 41 degrees C
      significantly reduces dantrolene reconstitution time. Further studies should
      evaluate the efficacy of dantrolene reconstituted with warmed diluent.

PMID- 16905076
TI  - Do race, gender, and source of payment impact on anesthetic technique for
      inguinal hernia repair?
AB  - STUDY OBJECTIVE: To evaluate the potential differences in the type of anesthesia
      provided to patients of different race, gender, and source of payment undergoing
      inguinal hernia repair (IHR). DESIGN: Retrospective cohort study. SETTING:
      Ambulatory surgical centers/National Survey of Ambulatory Surgery. PATIENTS: 5810
      patients older than 14 years who underwent IHR in an ambulatory surgical center.
      INTERVENTIONS: Inguinal hernia repair under different types of anesthesia.
      MEASUREMENTS: The association of race, gender, and source of payment with
      different types of anesthesia for IHR as determined by multivariate regression
      analysis. RESULTS: Significant discrepancies in the use of various anesthetics
      between patients of different race, gender, and source of payment were found.
      Patients identified as black and those of other minority groups were
      significantly more likely to receive general anesthesia compared with those
      identified as white (odds ratio [OR] 2.76, confidence interval [CI] 1.96-3.88 and
      OR 1.66, CI 1.14-2.42, respectively). Those identified as black were less likely
      to receive epidural anesthesia compared with their white counterparts (OR 0.36,
      CI 0.14-0.95). Women were less likely than men to undergo IHR with epidural
      anesthesia (OR 0.5, 95% CI 0.3-0.85). CONCLUSION: Significant discrepancies in
      the use of various anesthetics for IHR between patients of different race,
      gender, and insurance status were found. Despite limitations inherent to
      secondary data analysis, the findings raise the possibility that nonmedical
      factors may influence anesthetic management.

PMID- 16905077
TI  - Prevention of withdrawal associated with the injection of rocuronium in adults
      and children.
AB  - STUDY OBJECTIVE: To determine which technique prevents the withdrawal associated
      with rocuronium administration in adults and children. DESIGN: Blinded,
      randomized, prospective trial. SETTING: This study was set at an inpatient
      anesthesia in a university teaching hospital. PATIENTS: 200 adult patients (aged
      19-63 years) and 150 children (aged 2-9 years) undergoing elective surgery
      requiring endotracheal intubation. INTERVENTIONS: Four groups in adult and 3
      groups in children of 50 patients each were investigated. In adult study, control
      groups with free intravenous (IV) flow (C-F) or the occlusion of IV flow (C-O)
      received saline as the pretreatment of rocuronium; lidocaine groups with free IV
      flow (L-F) or the occlusion of IV flow (L-O) received lidocaine as the
      pretreatment of rocuronium, preceded by thiopental 5 seconds before. In children
      study, groups P and L received saline and lidocaine as the pretreatment of
      rocuronium, respectively, and group S received rocuronium mixed with sodium
      bicarbonate after the pretreatment of placebo preceded by thiopental.
      MEASUREMENTS AND MAIN RESULTS: The patient's response to rocuronium injection was
      graded using a 4-point scale. The pH and osmolality of treatment solution were
      measured. The incidence of no movement after rocuronium was 96% in L-O, 46% in L
      F, 26% in C-O, and 18% in C-F in adult and 96% in S, 58% in L, and 8% in P in
      children. CONCLUSIONS: Withdrawal after rocuronium can be eliminated by the
      pretreatment of lidocaine during the occlusion of the IV flow in adults and
      addition of sodium bicarbonate in children.

PMID- 16905079
TI  - Effect of xenon on catecholamine and hemodynamic responses to surgical noxious
      stimulation in humans.
AB  - STUDY OBJECTIVE: To determine the effect of xenon in combination anesthesia with
      sevoflurane on the catecholamine and hemodynamic responses to surgical noxious
      stimulation in humans. DESIGN: Randomized study. SETTING: A university hospital.
      PATIENTS: This study involved 32 female ASA physical status I and II patients,
      age 20-58 years, scheduled for abdominal hysterectomy. INTERVENTIONS: Patients
      were randomly divided into 4 groups: group X50-S1.5, 50% xenon and 1.5%
      sevoflurane; group X70-S1.5, 70% xenon and 1.5% sevoflurane; group G70-S1.5, 70%
      nitrous oxide and 1.5% sevoflurane; and group S2.8, 2.8% sevoflurane. No
      premedication was administered to the patients, and anesthesia was induced by
      administration of sevoflurane in oxygen and 0.10 to 0.15 mg/kg of vecuronium.
      After tracheal intubation, the combination of anesthetics was started, and skin
      incision was performed after equilibration for more than 15 minutes.
      MEASUREMENTS: Systolic blood pressure and heart rate (HR) were recorded, and the
      plasma concentrations of norepinephrine, epinephrine (E), and dopamine were
      measured 0, 2.5, 5, 7.5, 10, 12.5, and 15 minutes after skin incision. MAIN
      RESULTS: The maximal increase in the E concentration and the values of the area
      under the curve for E were significantly smaller in the X50-S1.5 and X70-S1.5
      groups compared with that in the S2.8 group (P<0.05). At 1 minute after incision,
      the HR in X50-S1.5 was significantly lower than those in G70-S1.5 and S2.8 groups
      and the HR in X70-S1.5 was lower than that in S2.8 group (P<0.01). The systolic
      blood pressure in S2.8 group at 1 minute was significantly higher than those of
      other groups (P<0.01). CONCLUSION: Combination anesthesia using xenon and
      sevoflurane suppresses the plasma E concentration and hemodynamic response after
      skin incision more effectively than sevoflurane anesthesia alone.

PMID- 16905080
TI  - High-frequency jet ventilation in interventional bronchoscopy: factors with
      predictive value on high-frequency jet ventilation complications.
AB  - STUDY OBJECTIVE: To evaluate the incidence and impact on clinical outcome of
      complications observed during high-frequency jet ventilation (HFJV) at
      interventional bronchoscopy and to identify the perioperative factors that may be
      associated to an increased incidence of such complications. DESIGN: Observational
      retrospective, study with an observational prospective validation of the
      statistically significant associations. SETTING: University hospital. PATIENTS:
      The retrospective study involved 276 patients who underwent an interventional
      rigid bronchoscopy during general anesthesia and HFJV. Forty consecutive patients
      were accrued for the prospective validation group. INTERVENTIONS/MEASUREMENTS:
      Information recorded included patient medical history and perioperative
      complications observed at HFJV-managed bronchoscopic procedures and their impact
      on clinical outcome until hospital discharge. MAIN RESULTS: At least one
      complication was detected in 38% of retrospective patients and 55% of prospective
      patients. Most frequent complications were hypercapnia, hypoxemia, and
      hemodynamic instability, but just one case of barotrauma in the retrospective
      group. Despite the high incidence, these complications were transient and did not
      increase hospital stay, whereas technical failure to widen airway lumen was
      associated with an adverse prognosis. Several clinical parameters showed a
      significant association with complications in the univariate analysis. However,
      the multivariate analysis only evidenced two independent predictive factors: the
      ASA physical status scale and baseline oxygen saturation. CONCLUSIONS:
      Classification in ASA physical status IV group and a baseline oxygen saturation
      of 95% or less independently predicted the development of complications during
      interventional rigid bronchoscopy with HFJV.

PMID- 16905070
TI  - Category 5: Class II Division 1 malocclusion with a high mandibular plane angle.
AB  - This case report was submitted to the American Board of Orthodontics as part of
      the board-certification process. The summary of treatment and records are
      reprinted here much as they were submitted to the board.

PMID- 16905081
TI  - Comparison of direct and video-assisted views of the larynx during routine
      intubation.
AB  - OBJECTIVE: To compare the direct and indirect (video monitor) views of the
      glottic opening using a new Macintosh blade that is modified to provide a video
      image of airway structures during laryngoscopy. DESIGN: Prospective multicenter
      trial. SETTING: 11 university-affiliated hospitals. PATIENTS: 867 adults
      undergoing elective surgery requiring general anesthesia and tracheal intubation.
      INTERVENTIONS: Patients received general anesthesia and were paralyzed. Direct
      laryngoscopy was supervised by one of the investigators at each institution. The
      best possible view was obtained with a Macintosh video laryngoscope during direct
      vision using standard techniques such as external laryngeal manipulation and
      backward, upward, and rightward pressure, if necessary. The laryngoscopist then
      looked at the video monitor and performed any necessary maneuvers to obtain the
      best view on the video monitor. Thus, 2 assessments were made during the same
      laryngoscopy (direct naked-eye view vs video monitor view). Tracheal intubation
      was then performed using the monitor view. Glottic views were rated according to
      the Cormack-Lehane scoring system, as modified by Yentis and Lee. A questionnaire
      was completed for each patient. MEASUREMENTS AND MAIN RESULTS: Data from 865
      patients were suitable for analysis. Visualization was considered easy (Cormack
      Lehane score<3) in 737 patients and difficult (Cormack-Lehane score=3 or 4) in 21
      for both direct and video-assisted views. In 7 patients, the view was considered
      easy during direct visualization yet difficult on the video monitor view. On the
      other hand, the view was considered difficult in 100 patients during direct
      visualization yet easy on the video monitor view (P<0.001). CONCLUSIONS: Video
      assisted laryngoscopy provides an improved view of the larynx, as compared with
      direct visualization. This technique may be useful for cases of difficult
      intubation and reintubation as well as for teaching laryngoscopy and intubation.

PMID- 16905082
TI  - Elective surgery days after myocardial infarction: clinical and ethical
      considerations.
AB  - We present an unusual case of verified myocardial infarction without surgery.
      Successful elective lumbar spine surgery was performed 4 days post-myocardial
      infarction during perioperative beta-blockade, after cardiology evaluation
      recommended surgery without further evaluation. Clinical and ethical
      considerations are discussed.

PMID- 16905083
TI  - Cardiovascular collapse due to massive pulmonary thromboembolism during
      orthotopic liver transplantation.
AB  - Severe pulmonary thromboembolism has been occasionally reported during orthotopic
      liver transplantation, with fatal outcomes occurring in about 50% of cases
      because of low cardiac output and multiple organ failure. Perioperative
      alterations in coagulation, insertion of pulmonary artery and other invasive
      catheters, administration of antifibrinolytic agents, and repeated ischemic
      insults may all promote the formation of intravascular/cardiac blood clots. We
      present a case of intraoperative right ventricular failure associated with the
      presence of a large thrombus wrapped around the pulmonary artery catheter.
      Identification of risk factors for intraoperative pulmonary thromboembolism
      warrants a prophylactic medical approach including selective blood component
      therapy and administration of antifibrinolytics guided by bedside coagulation
      tests as well as noninvasive hemodynamic monitoring.

PMID- 16905086
TI  - Liposuction: contemporary issues for the anesthesiologist.
AB  - Liposuction is a procedure that has emerged over the last 30 years as a method to
      remove subcutaneous fat for cosmetic purposes. Numerous liposuction techniques
      have been developed and the purpose of this article is to examine one such
      technique: "tumescent liposuction." Tumescent liposuction involves using large
      volumes of dilute local anesthetic and epinephrine to facilitate anesthesia and
      decrease blood loss. Questions remain about the appropriate dose of local
      anesthetic, the use of general anesthesia in liposuction, and the setting in
      which the chosen liposuction method is used. This article also attempts to shed
      light on this burgeoning field.

PMID- 16905084
TI  - Anesthetic management of an AAI pacemaker patient with paroxysmal atrial
      fibrillation during colorectal surgery.
AB  - Perioperative management of patients with cardiac pacemakers may be challenging
      because of the increasing sophistication of these devices. We report a case of a
      patient with paroxysmal atrial fibrillation (PAF) and with a permanent AAIR
      (bipolar atrial-inhibited adaptive rate) pacemaker who suffered life-threatening
      episodes of arrhythmias during operation. The first episode was vagally induced
      PAF during bowel manipulation; the second, induced by the increased pacing
      threshold from the external electric cardioversion and hyperkalemia.
      Transcutaneous pacing provided cardiac pacing and stabilized the patient during
      the second episode. Thorough preoperative evaluation and prophylactic placement
      of temporary pacing or at least transcutaneous pacing are important for the
      avoidance and minimization of intraoperative complications in patients with sick
      sinus syndrome and with an AAI (atrial inhibited) pacemaker.

PMID- 16905085
TI  - Post-dural headache associated with thoracic paravertebral blocks.
AB  - The thoracic paravertebral block is effective in providing anesthesia and
      postoperative analgesia for thoracic and abdominal surgeries. This case report
      describes a suspected post-dural puncture headache following bilateral thoracic
      paravertebral blocks for postoperative analgesia after an umbilical hernia
      repair.

PMID- 16905087
TI  - The history of subcutaneous oxygen therapy.
AB  - Soon after the discovery of oxygen, experiments began on the use of oxygen for
      therapeutic purposes, including subcutaneous administration of oxygen, on humans
      and animals. The history of subcutaneous oxygen therapy (SQOT) is examined in the
      context of the growing understanding of the use and methods of oxygen
      administration. Little was written about this therapy until the 19th century,
      despite an advocacy for its use in some circles. There was resurgence in the use
      of SQOT in the early 20th century. Investigators in the field of anesthesia,
      including such notable figures as Paul M. Wood, Ralph M. Waters, and John Henry
      Evans, contributed to the growth in popularity of the therapy and to the
      literature on the subject. Although SQOT has been supplanted by other means of
      administration, it may have a role in management of some inflammatory or pain
      conditions.

PMID- 16905089
TI  - Depth of the thoracic epidural space in 1776 patients using the paramedian
      approach.

PMID- 16905090
TI  - Hill block, a modification of the Bier block.

PMID- 16905091
TI  - Exchange of a double-lumen endobronchial tube using fiber-optic laryngoscopy
      (WuScope) in a difficult intubation patient.

PMID- 16905092
TI  - Central anticholinergic syndrome strikes again.

PMID- 16905094
TI  - Sirtuins caught in the act.

PMID- 16905093
TI  - Use and limitations of the Cohen endobronchial blocker.

PMID- 16905095
TI  - Gaining access to ERp57 function.

PMID- 16905096
TI  - A steric antagonism of actin polymerization by a salmonella virulence protein.
AB  - Salmonella spp. require the ADP-ribosyltransferase activity of the SpvB protein
      for intracellular growth and systemic virulence. SpvB covalently modifies actin,
      causing cytoskeletal disruption and apoptosis. We report here the crystal
      structure of the catalytic domain of SpvB, and we show by mass spectrometric
      analysis that SpvB modifies actin at Arg177, inhibiting its ATPase activity. We
      also describe two crystal structures of SpvB-modified, polymerization-deficient
      actin. These structures reveal that ADP-ribosylation does not lead to dramatic
      conformational changes in actin, suggesting a model in which this large family of
      toxins inhibits actin polymerization primarily through steric disruption of
      intrafilament contacts.

PMID- 16905097
TI  - Insights into the sirtuin mechanism from ternary complexes containing NAD+ and
      acetylated peptide.
AB  - Sirtuin proteins comprise a unique class of NAD+-dependent protein deacetylases.
      Although several structures of sirtuins have been determined, the mechanism by
      which NAD+ cleavage occurs has remained unclear. We report the structures of
      ternary complexes containing NAD+ and acetylated peptide bound to the bacterial
      sirtuin Sir2Tm and to a catalytic mutant (Sir2Tm(H116Y)). NAD+ in these
      structures binds in a conformation different from that seen in previous
      structures, exposing the alpha face of the nicotinamide ribose to the carbonyl
      oxygen of the acetyl lysine substrate. The NAD+ conformation is identical in both
      structures, suggesting that proper coenzyme orientation is not dependent on
      contacts with the catalytic histidine. We also present the structure of
      Sir2Tm(H116A) bound to deacteylated peptide and 3'-O-acetyl ADP ribose. Taken
      together, these structures suggest a mechanism for nicotinamide cleavage in which
      an invariant phenylalanine plays a central role in promoting formation of the O
      alkylamidate reaction intermediate and preventing nicotinamide exchange.

PMID- 16905098
TI  - The open state gating mechanism of gramicidin a requires relative opposed monomer
      rotation and simultaneous lateral displacement.
AB  - The gating mechanism of the open state of the gramicidin A (gA) channel is
      studied by using a new Monte Carlo Normal Mode Following (MC-NMF) technique, one
      applicable even without a target structure. The results demonstrate that the
      lowest-frequency normal mode (NM) at approximately 6.5 cm(-1) is the crucial mode
      that initiates dissociation. Perturbing the gA dimer in either direction along
      this NM leads to opposed, nearly rigid-body rotations of the gA monomers around
      the central pore axis. Tracking this NM by using the eigenvector-following
      technique reveals the channel's gating mechanism: dissociation via relative
      opposed monomer rotation and simultaneous lateral displacement. System evolution
      along the lowest-frequency eigenvector shows that the large-amplitude motions
      required for gating (dissociation) are not simple relative rigid-body motions of
      the monomers. Gating involves coupling intermonomer hydrogen bond breaking,
      backbone realignment, and relative monomer tilt with complex side chain
      reorganization at the intermonomer junction.

PMID- 16905100
TI  - Origin of exopolyphosphatase processivity: Fusion of an ASKHA phosphotransferase
      and a cyclic nucleotide phosphodiesterase homolog.
AB  - The Escherichia coli Ppx protein is an exopolyphosphatase that degrades long
      chain polyphosphates in a highly processive reaction. It also hydrolyzes the
      terminal 5' phosphate of the modified nucleotide guanosine 5' triphosphate 3'
      diphosphate (pppGpp). The structure of Ppx has been determined to 1.9 A
      resolution by X-ray crystallography. The exopolyphosphatase is an ASKHA (acetate
      and sugar kinases, Hsp70, actin) phosphotransferase with an active site found in
      a cleft between the two amino-terminal domains. Analysis of the active site
      indicates that among the ASKHA phosphotranferases of known structure, Ppx is the
      closest to the ectonucleoside triphosphate diphosphohydrolases. A third domain
      forms a six-helix claw that is similar to the catalytic core of the eukaryotic
      cyclic nucleotide phosphodiesterases. Most of the 29 sulfate ions bound to the
      Ppx dimer occupy sites where the polyP chain likely binds. An aqueduct that
      passes through the enzyme provides a physical basis for the enzyme's high
      processivity.

PMID- 16905099
TI  - Prokaryotic type II and type III pantothenate kinases: The same monomer fold
      creates dimers with distinct catalytic properties.
AB  - Three distinct isoforms of pantothenate kinase (CoaA) in bacteria catalyze the
      first step in coenzyme A biosynthesis. The structures of the type II
      (Staphylococcus aureus, SaCoaA) and type III (Pseudomonas aeruginosa, PaCoaA)
      enzymes reveal that they assemble nearly identical subunits with actin-like folds
      into dimers that exhibit distinct biochemical properties. PaCoaA has a fully
      enclosed pantothenate binding pocket and requires a monovalent cation to weakly
      bind ATP in an open cavity that does not interact with the adenine nucleotide.
      Pantothenate binds to an open pocket in SaCoaA that strongly binds ATP by using a
      classical P loop architecture coupled with specific interactions with the adenine
      moiety. The PaCoaA*Pan binary complex explains the resistance of bacteria
      possessing this isoform to the pantothenamide antibiotics, and the similarity
      between SaCoaA and human pantothenate kinase 2 explains the molecular basis for
      the development of the neurodegenerative phenotype in three mutations in the
      human protein.

PMID- 16905104
TI  - The notch ankyrin domain folds via a discrete, centralized pathway.
AB  - The Notch ankyrin repeat domain contains seven ankyrin sequence repeats, six of
      which adopt very similar structures. To determine if folding proceeds along
      parallel pathways and the order in which repeats become structured during
      folding, we examined the effect of analogous destabilizing Ala-->Gly
      substitutions in each repeat on folding kinetics. We find that folding proceeds
      to an on-pathway kinetic intermediate through a transition state ensemble
      containing structure in repeats three through five. Repeats two, six, and seven
      remain largely unstructured in this intermediate, becoming structured in a second
      kinetic step that leads to the native state. These data suggest that the Notch
      ankyrin domain folds according to a discrete kinetic pathway despite structural
      redundancy in the native state and highlight the importance of sequence-specific
      interactions in controlling pathway selection. This centralized pathway roughly
      corresponds to a low energy channel through the experimentally determined energy
      landscape.

PMID- 16905102
TI  - Structural basis for phosphotyrosine recognition by suppressor of cytokine
      signaling-3.
AB  - Suppressor of cytokine signaling (SOCS) proteins are indispensable negative
      regulators of cytokine-stimulated Janus kinase (JAK)-signal transducer and
      activator of transcription (STAT) signaling pathways. SOCS proteins (SOCS1-7 and
      CIS) consist of a variable N-terminal region, a central Src homology-2 (SH2)
      domain, and a C-terminal SOCS box. The N-terminal region in SOCS1 and SOCS3
      includes the so-called kinase inhibitory region that has been shown to inhibit
      the catalytic activity of JAK2. Here, we present a crystal structure at 2.0 A
      resolution of the N-terminally extended SH2 domain of SOCS3 in complex with its
      phosphopeptide target on the cytokine receptor gp130. The structure reveals that
      major insertions in the EF and BG loops of the SOCS3 SH2 domain are responsible
      for binding to gp130 with high affinity and specificity. In addition, the
      structure provides insights into the possible mechanisms by which SOCS3 and SOCS1
      inhibit JAK2 kinase activity.

PMID- 16905103
TI  - Structural basis of ubiquitin recognition by the deubiquitinating protease USP2.
AB  - Deubiquitinating proteases reverse protein ubiquitination and rescue their target
      proteins from destruction by the proteasome. USP2, a cysteine protease and a
      member of the ubiquitin specific protease family, is overexpressed in prostate
      cancer and stabilizes fatty acid synthase, which has been associated with the
      malignancy of some aggressive prostate cancers. Here, we report the structure of
      the human USP2 catalytic domain in complex with ubiquitin. Ubiquitin uses two
      major sites for the interaction with the protease. Both sites are required
      simultaneously, as shown by USP2 inhibition assays with peptides and ubiquitin
      mutants. In addition, a layer of ordered water molecules mediates key
      interactions between ubiquitin and USP2. As several of those molecules are found
      at identical positions in the previously solved USP7/ubiquitin-aldehyde complex
      structure, we suggest a general mechanism of water-mediated ubiquitin recognition
      by USPs.

PMID- 16905105
TI  - Knowledge-based real-space explorations for low-resolution structure
      determination.
AB  - The accurate and effective interpretation of low-resolution data in X-ray
      crystallography is becoming increasingly important as structural initiatives turn
      toward large multiprotein complexes. Substantial challenges remain due to the
      poor information content and ambiguity in the interpretation of electron density
      maps at low resolution. Here, we describe a semiautomated procedure that employs
      a restraint-based conformational search algorithm, RAPPER, to produce a starting
      model for the structure determination of ligase interacting factor 1 in complex
      with a fragment of DNA ligase IV at low resolution. The combined use of
      experimental data and a priori knowledge of protein structure enabled us not only
      to generate an all-atom model but also to reaffirm the inferred sequence
      registry. This approach provides a means to extract quickly from experimental
      data useful information that would otherwise be discarded and to take into
      account the uncertainty in the interpretation--an overriding issue for low
      resolution data.

PMID- 16905101
TI  - Crystal structure of rab11 in complex with rab11 family interacting protein 2.
AB  - The small GTPase Rab11 regulates the recycling of endosomes to the plasma
      membrane via interactions with the Rab11 family of interacting proteins (FIPs).
      FIPs contain a highly conserved Rab binding domain (RBD) at their C termini whose
      structure is unknown. Here, we have determined the crystal structure of the RBD
      of FIP2 in complex with Rab11(GTP) by single wavelength anomalous diffraction
      methods. The overall structure is a heterotetramer with dyad symmetry, arranged
      as a Rab11-(FIP2)2-Rab11 complex. FIP2 forms a central alpha-helical coiled coil,
      with both helices contributing to the Rab11 binding patch on equivalent and
      opposite sides of the homodimer. Switch 1 of Rab11 is embedded between the two
      helices, while switch 2 remains flexible and is peripherally associated with the
      effector. The complex reveals the structural basis for Rab11 recognition by FIPs
      and suggests the molecular mechanisms underlying endocytic recycling pathways.

PMID- 16905106
TI  - The crystal structure of the costimulatory OX40-OX40L complex.
AB  - OX40 is a T cell costimulator activated by OX40L. Blockade of the OX40L-OX40
      interaction has ameliorative effects in animal models of T cell pathologies. In
      order to better understand the interaction between OX40 and OX40L, we have
      determined the crystal structure of murine OX40L and of the human OX40-OX40L
      complex at 1.45 and 2.4 A, respectively. These structures show that OX40L is an
      unusually small member of the tumor necrosis factor superfamily (TNFSF). The
      arrangement of the OX40L protomers forming the functional trimer is atypical and
      differs from that of other members by a 15 degrees rotation of each protomer with
      respect to the trimer axis, resulting in an open assembly. Site-directed changes
      of the interfacial residues of OX40L suggest this interface lacks a single "hot
      spot" and that instead, binding energy is dispersed over at least two distinct
      areas. These structures demonstrate the structural plasticity of TNFSF members
      and their interactions with receptors.

PMID- 16905107
TI  - Crystal structure of the bb' domains of the protein disulfide isomerase ERp57.
AB  - The synthesis of proteins in the endoplasmic reticulum (ER) is limited by the
      rate of correct disulfide bond formation. This process is carried out by protein
      disulfide isomerases, a family of ER proteins which includes general enzymes such
      as PDI that recognize unfolded proteins and others that are selective for
      specific proteins or classes. Using small-angle X-ray scattering and X-ray
      crystallography, we report the structure of a selective isomerase, ERp57, and its
      interactions with the lectin chaperone calnexin. Using isothermal titration
      calorimetry and NMR spectroscopy, we show that the b' domain of ERp57 binds
      calnexin with micromolar affinity through a conserved patch of basic residues.
      Disruption of this binding site by mutagenesis abrogates folding of RNase B in an
      in vitro assay. The relative positions of the ERp57 catalytic sites and calnexin
      binding site suggest that activation by calnexin is due to substrate recruitment
      rather than a direct stimulation of ERp57 oxidoreductase activity.

PMID- 16905108
TI  - Amodal completion and visual holes (static and moving).
AB  - Occlusion is a frequent occurrence in a cluttered world of opaque objects. Often
      information about the shape of partly occluded objects can be gathered from the
      visible portion of the object and in particular its contours. Here we address the
      case where a region of a surface is visible exclusively through an aperture
      (visual hole). We make several observations about the grouping of surface regions
      visible through holes, and the appearance of moving objects and holes. These
      observations support the view that holes are shape properties of the object-with
      hole.

PMID- 16905112
TI  - The Hofmeister series effect in adsorption of cationic surfactants--theoretical
      description and experimental results.
AB  - Interfacial properties of cationic surfactants show strong dependence on the type
      of surfactant counterion or on the type of anion of a salt added to the
      surfactant solution. In the paper, the models of ionic surfactant adsorption that
      can take into account ionic specific effects are reviewed. Model of ionic
      surfactant adsorption based on the assumption that the surfactant ions and
      counterions undergo nonequivalent adsorption within the Stern layer was selected
      to describe experimental surface tension isotherms of aqueous solutions of a
      number of cationic surfactants. The experimental isotherms for: n-alkyl
      trimethylammonium cationic surfactants, namely: C(16)TABr (CTABr or CTAB),
      C(16)TACl, C(16)TAHSO(4), C(10)TABr and C(12)TABr as well as decyl- and
      dodecylpyridinium salts with and without various electrolyte anions as Cl(-), Br(
      ), F(-), I(-), NO(3)(-), ClO(4)(-) and CH(3)COO(-) were described in terms of the
      model and a good agreement between the theory and experiment was obtained for a
      wide range of surfactants and added electrolyte concentrations. A very pronounced
      Hofmeister effect in dependence of surface tension of cationic surfactants on the
      type of anion was found. Analysing this dependence in terms of the proposed model
      of ionic surfactant adsorption, strong correlation between "anion surface
      activity" (the model parameter accounting for ion penetration into the Stern
      layer), and the ion polarizability was obtained. That suggests that the mechanism
      related to the dispersive interaction of polarized ion with electric field at
      interface is responsible for Hofmeister series effects in surface activity of
      cationic surfactants. The same mechanism was proposed recently to explain the
      dependence of surface tension increase with electrolyte concentration on anion
      and cation type.

PMID- 16905110
TI  - The perception of causality in infancy.
AB  - Michotte proposed a rationalist theory of the origin of the human capacity to
      represent causal relations among events. He suggested that the input analyzer
      that underlies the causal perception in launching, entraining, and expulsion
      events is innate and is the ultimate source of all causal representations. We
      review the literature on infant causal representations, providing evidence that
      launching, entraining and expulsion events are interpreted causally by young
      infants. However, there is as of yet no good evidence that these representations
      are innate. Furthermore, there is considerable evidence that these
      representations are not the sole source of the human capacity for causal
      representation.

PMID- 16905109
TI  - Measuring causal perception: connections to representational momentum?
AB  - In a collision between two objects, we can perceive not only low-level
      properties, such as color and motion, but also the seemingly high-level property
      of causality. It has proven difficult, however, to measure causal perception in a
      quantitatively rigorous way which goes beyond perceptual reports. Here we focus
      on the possibility of measuring perceived causality using the phenomenon of
      representational momentum (RM). Recent studies suggest a relationship between
      causal perception and RM, based on the fact that RM appears to be attenuated for
      causally 'launched' objects. This is explained by appeal to the visual
      expectation that a 'launched' object is inert and thus should eventually cease
      its movement after a collision, without a source of self-propulsion. We first
      replicated these demonstrations, and then evaluated this alleged connection by
      exploring RM for different types of displays, including the contrast between
      causal launching and non-causal 'passing'. These experiments suggest that the RM
      attenuation effect is not a pure measure of causal perception, but rather may
      reflect lower-level spatiotemporal correlates of only some causal displays. We
      conclude by discussing the strengths and pitfalls of various methods of measuring
      causal perception.

PMID- 16905111
TI  - Defining the origin of Plasmodium falciparum resistant dhfr isolates in Senegal.
AB  - We previously reported a high baseline prevalence of mutations in the dhfr and
      dhps genes of Plasmodium falciparum throughout Senegal. The highest prevalence of
      the triple dhfr pyrimethamine associated mutations were found in isolates
      obtained in the western part of the country near the capital city of Dakar. In
      this study, we sought out to determine the relatedness of dhfr wild type and
      mutated strains by analyzing three microsatellite regions upstream of the dhfr
      locus. Twenty-six of the 31 wild type strains had a unique microsatellite
      pattern. In contrast, of the 17 isolates containing the triple mutation in dhfr,
      11 had an identical microsatellite pattern. Diverse geographical isolates in
      Senegal containing the triple dhfr mutation have arisen from a limited number of
      ancestral strains. In addition, we demonstrate that these isolates have shared
      ancestry with the previously reported triple mutation haplotype found in
      Tanzania, South Africa, and southeast Asia. This common ancestry may have
      implications for the malaria control strategy for reducing the spread of
      sulfadoxine-pyrimethamine resistance in Senegal and elsewhere in Africa.

PMID- 16905114
TI  - Physicochemical characterization of a peptide deriving from the glycoprotein gp36
      of the feline immunodeficiency virus and its lipoylated analogue in micellar
      systems.
AB  - P59 is the Trp-rich 20-mer peptide ((767)L-G(786)), partial sequence of the
      membrane-proximal external region (MPER) of the FIV gp36. It has potent antiviral
      activity, possibly due to a mechanism that inhibits the fusion of the virus with
      the cell membranes. In the hypothesis that a lipophilic tail could enhance the
      adhesion of P59 to the membrane so improving its antiviral activity, we
      synthesized its lipoylated analogue lipo-P59. Fluorescence, CD and NMR
      investigations in membrane mimicking environments (such as SDS and DPC micelles)
      were aimed to assess the potential of the lipo-P59 lipophilic tail to affect the
      biophysical and conformational behaviour of the peptide. In vitro inhibitory
      assays using lymphoid cell cultures to check the antiviral activity of peptides
      were also performed. The data show that the biophysical properties and the
      conformational preferences of the peptides are not dramatically affected by the
      hydrophobic tail, suggesting that the lipopeptide is capable of preserving all
      the biophysical peculiarities. Similarly, antiviral experimental data show that
      the membrane-anchored lipo-P59 peptide is also effective in inhibiting virus
      replication. Moreover, the lipophilic tail allows P59 to preserve its antiviral
      activity even in conditions in which the non lipoylated peptide is devoid of
      activity. In accordance with the unusual high Trp presence, the peptides confirm
      the preference to be positioned on the membrane interface. Furthermore, the data
      point out a peculiarity of interaction of the peptides with SDS as compared with
      DPC.

PMID- 16905116
TI  - Non-treatment-related sudden gains in depression: the role of self-evaluation.
AB  - A number of studies have demonstrated that recovery from depression is often
      marked by precipitous improvements during the course of treatment. The present
      research examined sudden gains occurring outside of the context of treatment in a
      sample of college students with current major depressive disorder (n=60), and
      tested whether variables pertaining to cognitive style, hope, self-evaluation,
      and life events would be associated with these gains. Results indicated that 60%
      of the sample experienced sudden gains, with over half of those sudden gains
      reversing before the end of the 9-week observation period. Sudden gainers were
      significantly less depressed at the end of the observation period but were no
      more likely to have achieved remission compared to non-sudden gainers. Although
      changes in cognitive style did not precede sudden gains, individuals with sudden
      gains had significantly higher self-esteem at baseline compared to non-sudden
      gainers. Furthermore, decreases in the frequency of social comparison occurred in
      the week prior to sudden gains. These results suggest that sudden gains do occur
      outside of the context of treatment and that self-evaluation processes may play
      an important role in recovery from depression.

PMID- 16905117
TI  - Parkin affects mitochondrial function and apoptosis in neuronal and myogenic
      cells.
AB  - We investigated the effect of parkin on mitochondrial function and apoptosis in
      SH-SY5Y, L6, RD, and COS-1 cells. Wild-type parkin attenuated reactive oxygen
      species (ROS) production in SH-SY5Y cells and mutant parkin enhanced ROS
      production in SH-SY5Y and L6 cells. Reactive oxygen intermediates, that were
      detected in mitochondria, were decreased in cells with overexpression of parkin.
      Parkin prevented apoptosis and enhanced mitochondrial membrane potentials in SH
      SY5Y and L6 cells not in COS-1 cells. Expressions and enzymatic activities of
      mitochondrial respiratory chain complexes were not uniformly enhanced but those
      of complex 1 were selectively enhanced. The present results suggest the cell
      selective function of parkin, i.e., parkin possesses anti-apoptotic and anti
      oxidant function in neuronal or myogenic cells but not in kidney cells.

PMID- 16905119
TI  - Human Nogo-C overexpression induces HEK293 cell apoptosis via a mechanism that
      involves JNK-c-Jun pathway.
AB  - The neurite outgrowth inhibitor protein Nogo-A has been identified as an
      inhibitor of axonal regeneration, and Nogo-B as a regulator of vasculature
      remodeling, but the additional roles of Nogo isoforms, especially Nogo-C, have
      obtained little attention. Nogo-C is weakly expressed in liver and kidney
      compared to the high expression in skeletal muscle. Here we detected the weak
      expression of Nogo-C in human embryonic kidney cell line HEK293, and found that
      Nogo-C expressed in HEK293 could induce cell apoptosis. Further experiments
      demonstrated the activation of JNK/SAPK and c-Jun, but not p38 in Nogo-C
      expressed cells. And JNK-specific inhibitor SP600125 could reduce cell apoptosis
      induced by Nogo-C. Furthermore, the activation of caspase-3 and PARP, the
      expression and phosphorylation of p53 were also detected. The data first revealed
      Nogo-C expressed in HEK293 confers apoptosis by inducing caspase-3 and p53
      activation through the JNK-c-Jun-dependent pathway.

PMID- 16905115
TI  - Extra domains in secondary transport carriers and channel proteins.
AB  - "Extra" domains in members of the families of secondary transport carrier and
      channel proteins provide secondary functions that expand, amplify or restrict the
      functional nature of these proteins. Domains in secondary carriers include TrkA
      and SPX domains in DASS family members, DedA domains in TRAP-T family members
      (both of the IT superfamily), Kazal-2 and PDZ domains in OAT family members (of
      the MF superfamily), USP, IIA(Fru) and TrkA domains in ABT family members (of the
      APC superfamily), ricin domains in OST family members, and TrkA domains in AAE
      family members. Some transporters contain highly hydrophilic domains consisting
      of multiple repeat units that can also be found in proteins of dissimilar
      function. Similarly, transmembrane alpha-helical channel-forming proteins contain
      unique, conserved, hydrophilic domains, most of which are not found in carriers.
      In some cases the functions of these domains are known. They may be ligand
      binding domains, phosphorylation domains, signal transduction domains,
      protein/protein interaction domains or complex carbohydrate-binding domains.
      These domains mediate regulation, subunit interactions, or subcellular targeting.
      Phylogenetic analyses show that while some of these domains are restricted to
      closely related proteins derived from specific organismal types, others are
      nearly ubiquitous within a particular family of transporters and occur in a
      tremendous diversity of organisms. The former probably became associated with the
      transporters late in the evolutionary process; the latter probably became
      associated with the carriers much earlier. These domains can be located at either
      end of the transporter or in a central region, depending on the domain and
      transporter family. These studies provide useful information about the evolution
      of extra domains in channels and secondary carriers and provide novel clues
      concerning function.

PMID- 16905120
TI  - Down-regulation of integrin alpha M beta 2 ligand-binding function by the
      urokinase-type plasminogen activator receptor.
AB  - The cell adhesion molecule integrin alphaMbeta2 associates with the urokinase
      type plasminogen activator receptor (uPAR) on monocytes and neutrophils. uPAR
      also associates with members of the beta1 and beta3 integrins, and it modulates
      the ligand-binding function of these integrins. In this study, we showed that co
      expressing uPAR with alphaMbeta2 in 293 transfectants down-regulated the ligand
      binding capacity of alphaMbeta2 to denatured protein, fibrinogen, and
      intercellular adhesion molecule 1 (ICAM-1). Migration of transfectants on
      fibrinogen mediated by alphaMbeta2 was reduced in the presence of uPAR. In
      addition, the constitutive ligand-binding property of an alphaMbeta2 mutant was
      attenuated by its association with uPAR. Co-immunoprecipitation analyses using a
      panel of alphaMbeta2-specific mAbs suggest shielding of the ligand-recognition
      site of alphaMbeta2 by uPAR.

PMID- 16905118
TI  - Splice variants of mIAP1 have an enhanced ability to inhibit apoptosis.
AB  - c-IAP1 is a member of the Inhibitor of Apoptosis protein family. Functions
      ascribed to c-IAP1 include inhibition of apoptosis and activation of NF-kappaB.
      Herein, we show that murine c-IAP1 (mIAP1) undergoes alterative splicing,
      generating two truncated proteins; one that lacks the CARD and RING domains
      (mIAP1-DeltaCARDDeltaRING) and the other that lacks only the CARD domain (mIAP1
      DeltaCARD). mIAP1-DeltaCARDDeltaRING mRNA is expressed at 2-3% of the levels of
      full-length mIAP1 (FL-mIAP1) in mouse tissues, yet it encodes a protein that
      accumulates at 50-fold higher levels than the FL-mIAP1 in cultured cells. This
      protein has an enhanced ability to inhibit Bax-induced apoptosis, but does not
      activate an NF-kappaB reporter. In contrast to mIAP1-DeltaCARDDeltaRING, the
      mIAP1-DeltaCARD mRNA displays distinct tissue variation, ranging from 5% to 15%
      of the FL-mIAP1 mRNA levels and its levels increase in the mammary gland during
      involution. This isoform also has enhanced anti-apoptotic activity, but
      diminished NF-kappaB activation. In summary, mIAP1 is alternatively spliced,
      generating protein isoforms with distinct functional characteristics.

PMID- 16905123
TI  - Effects of apoE on neuronal signaling and APP processing in rodent brain.
AB  - We previously reported that primary neuronal cells treated with apolipoprotein E
      (apoE) or an apoE-derived peptide (EP) increased ERK activation and decreased JNK
      activation via apoE receptors. Here, we examined if the effects observed in vitro
      were observed in vivo. Similar to our observations in primary neurons, in vivo we
      found that injections of 2muM EP into the rat hippocampus increased the levels of
      ERK activation and decreased JNK activation. However, the time course of these
      effects was slower in vivo. Immunohistochemical analysis of the tissue showed
      prominently increased ERK phosphorylation and decreased JNK phosphorylation in
      neuronal cells throughout the hippocampus, particularly in the CA3 regions. To
      determine if apoE was endocytosed by neurons, we conjugated fluorescent
      microspheres with the EP and injected them into the rat hippocampus. After 7
      days, the microspheres were present in neurons. We also examined the in vivo
      effects of apoE on ApoEr2 and APP processing. EP and full-length apoE3 and apoE4
      increased C-terminal fragments of ApoEr2 and APP after a single injection,
      multiple injections, and chronic infusion paradigms. ApoE3 produced higher levels
      of ApoEr2 and APP C-terminal fragments than apoE4. These results demonstrate that
      apoE alters ApoEr2 and APP processing in vivo. The increase in ERK activation is
      consistent with a role for apoE in a neuronal response to stress, and the
      decrease in JNK activation suggests that apoE may have anti-apoptotic effects,
      over several days.

PMID- 16905122
TI  - Ibotenic acid lesions reduce noradrenergic activation in ventromedial
      hypothalamus during hypoglycemia.
AB  - Noradrenergic and GABAergic systems in the ventromedial hypothalamus (VMH) are
      activated during hypoglycemia and initiate part of the compensatory
      counterregulatory response. Norepinephrine (NE) terminals innervating the VMH
      originate in glucosensing hindbrain areas, but whether NE activity in the VMH is
      under local control or in the hindbrain is unclear. To elucidate the role of
      neurons intrinsic to the VMH on NE release in the VMH during hypoglycemia,
      ibotenic acid (IBO), an NMDA receptor agonist that selectively destroys cell
      bodies, was used. In a 2 x 2 factorial study, IBO (3-5 microg/0.5 microL) or
      vehicle was stereotaxically administered into the VMH of male Sprague-Dawley
      rats. One week later, NE concentration in the VMH was measured by microdialysis
      during insulin-induced hypoglycemia (2.0 U/kg) or euglycemia (saline control).
      Baseline levels of NE were not statistically different (p=0.10) in IBO-treated
      compared with vehicle-treated rats (13.3+/-2.8 nM vs. 7.9+/-1.1 nM). The initial
      increase in interstitial NE concentration during hypoglycemia in control rats was
      absent in IBO-treated rats (p<0.01). In IBO-treated hypoglycemic rats, NE
      concentrations increased after 45 min to a similar level observed in control rats
      during the first 20 min of hypoglycemia. These results are consistent with the
      suggestion that local neurons in the VMH respond to hypoglycemia and modify NE
      activation in the VMH during hypoglycemia.

PMID- 16905121
TI  - Injury to axons and oligodendrocytes following endothelin-1-induced middle
      cerebral artery occlusion in conscious rats.
AB  - Injury to axons and oligodendrocytes has been poorly characterized in most animal
      models of stroke, and hence has been difficult to target therapeutically. It is
      therefore necessary to characterize axonal and oligodendroglial injury in these
      models, in order to rationally design putative protective compounds that minimize
      this injury. This study aims to characterize injury to axons and oligodendrocytes
      in the endothelin-1 (ET-1) model of middle cerebral artery occlusion (MCAO) in
      conscious rats. Transient forebrain ischemia was induced in conscious adult male
      Long Evans rats by the perivascular microinjection of ET-1. Quantitative
      histopathology was performed on forebrain sections at 6, 24, 48 and 72 h after ET
      1 administration, using ballistic light analyses and immunohistochemistry for
      amyloid precursor protein (APP), SMI32, and Tau-1. Ballistic light analyses of
      cortical and striatal lesions revealed that the infarct volume was maximal in
      these regions by 6 h. APP and SMI32 immunohistochemistry demonstrated that axonal
      injury was maximal by 6 h in this model; however, some injured axons appeared to
      maintain good structural integrity up to 72 h after insult. Density measurements
      for Tau-1-immunopositive oligodendrocytes were significantly elevated within the
      corpus callosum from 48 h, but reductions in total oligodendrocyte numbers were
      not apparent up 72 h after ET-1 injection. These results indicate that axonal and
      oligodendroglial injury should be investigated as potential targets for delayed
      therapeutic intervention after MCAO.

PMID- 16905125
TI  - Do intrinsic arterial wall features determine atherosclerosis susceptibility?

PMID- 16905124
TI  - From gene networks underlying sex determination and gonadal differentiation to
      the development of neural networks regulating sociosexual behavior.
AB  - Genes are not expressed in isolation any more than social behavior has meaning
      outside of society. Both are in dynamic flux with the immediate environment that
      the gene/individual finds itself, which in turn establishes the timing, pattern,
      and conditions of expression. This means that complex behaviors and their genetic
      underpinnings should be viewed as a cumulative process, or as the result of
      experiences up to that point in time and, at the same time, as setting the stage
      for what will follow. The evidence indicates that as experiences accumulate
      throughout life, early experiences shape how genes/individuals will respond to
      later experiences, whereas later experiences modify the effects of these earlier
      experiences. A method of graphically representing and analyzing change in gene
      and neural networks is presented. Results from several animal model systems will
      be described to illustrate these methods. First, we will consider the phenomenon
      of temperature-dependent sex determination in reptiles. We will illustrate how
      the experience of a particular temperature during a sensitive period of
      embryogenesis sculpts not only the patterns of expression of genes involved in
      sex determination and gonadal differentiation but also the morphological,
      physiological, neuroendocrine, and behavioral traits of the adult phenotype. The
      second model system concerns the effects of the sex ratio in the litter in rats,
      and the genotype ratio in the litter of transgenic mice, on the nature and
      frequency of maternal care and how this in turn influences the patterns of
      activation of identified neural circuits subserving the offspring's sociosexual
      behavior when it is an adult.

PMID- 16905127
TI  - Lateralized cognition: asymmetrical and complementary strategies of pigeons
      during discrimination of the "human concept".
AB  - This study was aimed at revealing which cognitive processes are lateralized in
      visual categorizations of "humans" by pigeons. To this end, pigeons were trained
      to categorize pictures of humans and then tested binocularly or monocularly (left
      or right eye) on the learned categorization and for transfer to novel exemplars
      (Experiment 1). Subsequent tests examined whether they relied on memorized
      features or on a conceptual strategy, using stimuli composed of new combinations
      of familiar and novel humans and backgrounds (Experiment 2), whether the
      hemispheres processed global or local information, using pictures with different
      levels of scrambling (Experiment 3), and whether they attended to configuration,
      using distorted human figures (Experiment 4). The results suggest that the left
      hemisphere employs a category strategy and concentrates on local features, while
      the right hemisphere uses an exemplar strategy and relies on configuration. These
      cognitive dichotomies of the cerebral hemispheres are largely shared by humans,
      suggesting that lateralized cognitive systems already defined the neural
      architecture of the common ancestor of birds and mammals.

PMID- 16905129
TI  - Independent regulation of skeletal growth by Ihh and IGF signaling.
AB  - The insulin-like growth factors (IGFs) play a major role in regulating the
      systemic growth of mammals. However, it is unclear to what extent their systemic
      and/or local functions act in concert with other local growth factors controlling
      the sizes of individual organs. We have specifically addressed whether growth
      control of the skeleton by IGFs interacts genetically with that by Indian
      hedgehog (Ihh), a locally produced growth signal for the endochondral skeleton.
      Here, we report that disruption of both IGF and Ihh signaling resulted in
      additive reduction in the size of the embryonic skeleton. Thus, IGF and Ihh
      signaling appear to control the growth of the skeleton in parallel pathways.

PMID- 16905126
TI  - Integrated and automatic mixing of whole blood: an evaluation of a novel blood
      gas analyzer.
AB  - BACKGROUND: A homogeneous whole blood specimen is essential to produce quality
      results from blood gas analysis, however achieving an adequately mixed specimen
      can be difficult due to the absence of any dead space in a blood gas syringe.
      This study evaluated the efficacy of an automatic mixing feature incorporated
      into the ABL800 FLEX blood gas analyzer and estimated the systematic error in
      tests performed by the instrument. METHODS: Quantitative measurements of pH,
      PCO(2), PO(2), Na(+), K(+), Ca(+), glucose, lactate, and total hemoglobin were
      performed on 388 whole blood specimens collected into standard blood gas syringes
      or specific syringes designed to work in conjunction with the ABL800 FLEX. One
      hundred eighty specimens were manually or automatically mixed following
      horizontal storage for 10, 20, or 30 min and total hemoglobin was used as in
      indicator of specimen homogeneity. Two hundred eight specimens were used to
      estimate the systematic error of tests performed by the ABL800 FLEX. RESULTS:
      Manual mixing produced significantly more variation in paired hemoglobin
      measurements compared to automatic mixing at all three time points (p<0.0001).
      All estimates of systematic error were very low and clinically insignificant.
      Quantitative results showed excellent agreement with a reference analyzer.
      CONCLUSIONS: In contrast to manual mixing, automatic mixing by the ABL800 FLEX
      consistently produces a homogeneous specimen.

PMID- 16905128
TI  - Miranda couples oskar mRNA/Staufen complexes to the bicoid mRNA localization
      pathway.
AB  - The double-stranded RNA binding protein Staufen is required for the microtubule
      dependent localization of bicoid and oskar mRNAs to opposite poles of the
      Drosophila oocyte and also mediates the actin-dependent localization of prospero
      mRNA during the asymmetric neuroblast divisions. The posterior localization of
      oskar mRNA requires Staufen RNA binding domain 2, whereas prospero mRNA
      localization mediated the binding of Miranda to RNA binding domain 5, suggesting
      that different Staufen domains couple mRNAs to distinct localization pathways.
      Here, we show that the expression of Miranda during mid-oogenesis targets
      Staufen/oskar mRNA complexes to the anterior of the oocyte, resulting in bicaudal
      embryos that develop an abdomen and pole cells instead of the head and thorax.
      Anterior Miranda localization requires microtubules, rather than actin, and
      depends on the function of Exuperantia and Swallow, indicating that Miranda links
      Staufen/oskar mRNA complexes to the bicoid mRNA localization pathway. Since
      Miranda is expressed in late oocytes and bicoid mRNA localization requires the
      Miranda-binding domain of Staufen, Miranda may play a redundant role in the final
      step of bicoid mRNA localization. Our results demonstrate that different Staufen
      interacting proteins couple Staufen/mRNA complexes to distinct localization
      pathways and reveal that Miranda mediates both actin- and microtubule-dependent
      mRNA localization.

PMID- 16905130
TI  - Unique and redundant functions of C. elegans HP1 proteins in post-embryonic
      development.
AB  - HP1 proteins are essential components of heterochromatin and contribute to the
      transcriptional repression of euchromatic genes. Although most species contain
      more than one HP1 family member which differ in their chromosomal distribution,
      it is not known to what extent the activity of these different family members is
      redundant or specific in a developmental context. C. elegans has two HP1
      homologues, HPL-1 and HPL-2. While HPL-2 functions in vulval and germline
      development, no function has so far been attributed to HPL-1. Here we report the
      characterization of an hpl-1 null allele. We show that while the absence of hpl-1
      alone results in no obvious phenotype, hpl-1;hpl-2 double mutants show synthetic,
      temperature sensitive phenotypes including larval lethality and severe defects in
      the development of the somatic gonad. Furthermore, we find that hpl-1 has an
      unexpected role in vulval development by acting redundantly with hpl-2, but not
      other genes previously implicated in vulval development. Localization studies
      show that like HPL-2, HPL-1 is a ubiquitously expressed nuclear protein. However,
      HPL-1 and HPL-2 localization does not completely overlap. Our results show that
      HPL-1 and HPL-2 play both unique and redundant functions in post-embryonic
      development.

PMID- 16905131
TI  - Biphasic effect of apomorphine on rat nociception and effect of dopamine D2
      receptor antagonists.
AB  - Studies on the effect of dopaminergic agonists in behavioral measures of
      nociception have gathered numerous but rather conflicting data. We studied the
      effects of the D(1)/D(2) receptor agonist apomorphine, as well as the modulatory
      effects of (S)-(-)-sulpiride (selective D(2) receptor antagonist) and domperidone
      (peripheral D(2) receptor antagonist), on thermal, mechanical and chemical
      nociception on rats. Apomorphine induced a biphasic dose-response relationship,
      low doses producing hyperalgesia and high doses inducing antinociception. Tonic
      (chemical) pain was more sensitive to apomorphine than phasic (thermal and
      mechanical thresholds) pain. (S)-(-)-sulpiride, but not domperidone, fully
      antagonized the antinociceptive effect of apomorphine in all three measures of
      nociception, pointing to a participation of D(2) dopaminergic receptors for the
      antinociceptive action of apomorphine. Although spinal sites for dopaminergic
      ligands mechanistically may account for the effects observed, involvement of
      dopaminergic receptors of the forebrain could probably explain better the
      antinociceptive effects of apomorphine, especially in chemical tonic pain.

PMID- 16905132
TI  - The antinociceptive effect of salvinorin A in mice.
AB  - Salvia divinorum is a hallucinogenic plant used by the Mazatec Indians of Mexico
      for traditional spiritual ceremonies. The active constituent, salvinorin A,
      induces profound hallucinations, however the biological mechanism for this action
      is not known. Affinity-binding studies suggest that the biologic activity of
      salvinorin A involves the kappa-opioid receptor. The purpose of this study was to
      evaluate the antinociceptive effect of salvinorin A in mice. Salvinorin A and
      opioid receptor antagonists were administered intrathecally and the tail-flick
      latencies were used as a measure of antinociception. Salvinorin A increased tail
      flick latencies in a dose-dependent manner (13.9-23.1 nmol) compared to control
      trials. Pretreatment with the kappa-opioid receptor antagonist nor
      binaltorphimine attenuated the salvinorin A induced increase in tail-flick
      latency. In contrast, neither the mu-opioid receptor antagonist beta
      funaltrexamine nor delta-opioid receptor antagonist naltrindole significantly
      affected the antinociceptive response of salvinorin A administration. These data
      support previous reports that salvinorin A represents a unique non-alkaloidal
      agonist for the kappa-opioid receptor.

PMID- 16905133
TI  - Effects of nicotine on regional blood flow in the olfactory bulb in rats.
AB  - Effects of nicotine on blood flow in the olfactory bulb were examined in
      anesthetized rats. Nicotine administered intravenously at 100 microg/kg increased
      regional blood flow in the olfactory bulb, irrespective of changes in systemic
      arterial pressure. Nicotine administered locally into the internal carotid artery
      at 10 microg increased blood flow, without changing arterial pressure; this
      response was abolished by hexamethonium. These results indicate that nicotine
      produces vasodilatation in the olfactory bulb via activation of nicotinic
      receptors located close to the olfactory bulb. Nicotine may be of therapeutic
      value in improving blood flow in the olfactory bulb.

PMID- 16905134
TI  - Elevations in local gamma activity are accompanied by changes in the firing rate
      and information coding capacity of neurons in the region of the subthalamic
      nucleus in Parkinson's disease.
AB  - Local field potential (LFP) gamma (55-95 Hz) activity has been recorded in the
      vicinity of the subthalamic nucleus with both microelectrodes and macroelectrodes
      in patients with Parkinson's disease undergoing functional neurosurgery. Although
      this activity increases with movement its functional significance remains
      unknown. We hypothesised that elevations in local gamma activity might be
      associated with an increase in the capacity of individual spike trains to code
      information. Changes in the median firing frequency, entropy and baud were
      determined during spontaneous variations in the level of simultaneously recorded
      LFP gamma activity in a sample of 31 neurons. The latter were recorded from the
      zona incerta (n = 5) and subthalamic nucleus (n = 26) in 10 parkinsonian
      patients. Although 19% of neurons showed a decrease in firing rate, overall there
      was a net increase in spike frequency and baud of 18.0+/-5.5% and 16.9+/-5.3%,
      when periods of high gamma were compared to periods of low gamma LFP activity. In
      contrast, entropy dropped by only 0.8+/-0.2% across the sampled neuronal
      population during periods of high gamma. All net changes were significant. We
      conclude that overall there was a net elevation in firing rate and potential
      information coding capacity, assessed in terms of baud, amongst neurons during
      periods of elevated gamma LFP activity in the subthalamic region.

PMID- 16905137
TI  - Malaria in pregnancy: access to effective interventions in Africa.
AB  - Malaria infection during pregnancy (MIP) poses substantial risks to the mother,
      her fetus and the newborn. Consequences of MIP include severe anemia, placental
      parasitemia and intrauterine growth retardation, which contribute to low birth
      weight, a principal cause of infant mortality in the African region. Effective
      interventions for the prevention and control of MIP include Intermittent
      preventive treatment (IPT), Insecticide treated nets (ITNs), and case management,
      and are being deployed by countries. The global political and fiscal environment
      is favorable with increasing resources to support the scale-up of interventions.
      What is needed at country level is strong collaboration among malaria and
      reproductive health programs and partners, to maximize the use of available
      resources for scaling-up to achieve the Millennium Development Goals. Equally
      important is the need for continuous advocacy at all levels to keep malaria high
      on the global agenda and maintain the current global commitment and momentum.

PMID- 16905113
TI  - Factors influencing the energetics of electron and proton transfers in proteins.
      What can be learned from calculations.
AB  - A protein structure should provide the information needed to understand its
      observed properties. Significant progress has been made in developing accurate
      calculations of acid/base and oxidation/reduction reactions in proteins. Current
      methods and their strengths and weaknesses are discussed. The distribution and
      calculated ionization states in a survey of proteins is described, showing that a
      significant minority of acidic and basic residues are buried in the protein and
      that most of these remain ionized. The electrochemistry of heme and quinones are
      considered. Proton transfers in bacteriorhodopsin and coupled electron and proton
      transfers in photosynthetic reaction centers, 5-coordinate heme binding proteins
      and cytochrome c oxidase are highlighted as systems where calculations have
      provided insight into the reaction mechanism.

PMID- 16905135
TI  - Bradykinin activates ADP-ribosyl cyclase in neuroblastoma cells: intracellular
      concentration decrease in NAD and increase in cyclic ADP-ribose.
AB  - ADP-ribosyl cyclase activity in the crude membrane fraction of
      neuroblastomaxglioma NGPM1-27 hybrid cells was measured by monitoring [(3)H]
      cyclic ADP-ribose (cADPR) formation from [(3)H] NAD(+). Bradykinin (BK) at 100nM
      increased ADP-ribosyl cyclase activity by about 2.5-fold. Application of 300nM BK
      to living NGPM1-27 cells decreased NAD(+) to 78% of the prestimulation level at
      30s. In contrast, intracellular cADPR concentrations were increased by 2-3-fold
      during the period from 30 to 120s after the same treatment. Our results suggest
      that cADPR is one of the second messengers downstream of B(2) BK receptors.

PMID- 16905136
TI  - The AtNFXL1 gene encodes a NF-X1 type zinc finger protein required for growth
      under salt stress.
AB  - The human NF-X1 protein and homologous proteins in eukaryotes represent a class
      of transcription factors which are characterised by NF-X1 type zinc finger
      motifs. The Arabidopsis genome encodes two NF-X1 homologs, which we termed
      AtNFXL1 and AtNFXL2. Growth and survival was impaired in atnfxl1 knock-out
      mutants and AtNFXL1-antisense plants under salt stress in comparison to wild-type
      plants. In contrast, 35S: :AtNFXL1 plants showed higher survival rates. The
      AtNFXL2 protein potentially plays an antagonistic role. The Arabidopsis NF-X1
      type zinc finger proteins likely are part of regulatory mechanisms, which protect
      major processes such as photosynthesis.

PMID- 16905138
TI  - Partial suppression of CETP activity beneficially modifies the lipid transfer
      profile of plasma.
AB  - Cholesteryl ester transfer protein (CETP) regulates human lipoprotein metabolism.
      Because reducing CETP increases plasma HDL, CETP inhibitors are currently being
      investigated for their pharmacologic value. However, complete CETP deficiency may
      have undesirable consequences. In contrast, based on previous studies with
      purified components, we hypothesized that partial CETP inhibition, which will
      still elevate HDL, may induce beneficial changes in plasma lipid metabolism. To
      address this, CETP activity in human plasma was variably inhibited with
      monoclonal antibody. In control plasma, VLDL to LDL lipid transfer was >2-fold
      higher than to HDL(3) with lipid transfer to HDL(2) intermediate. However,
      individual lipid transfer events were uniquely sensitive to CETP suppression such
      that when CETP activity was inhibited by 60%, lipid transfer from VLDL to LDL,
      HDL(2) and HDL(3) were equal. The ratio of lipid transfers to LDL versus HDL
      declined linearly with CETP inhibition. In mass lipid transfer experiments, 25
      50% inhibition of CETP significantly reduced lipid flux between VLDL and LDL but
      minimally affected cholesteryl ester (CE) loss from HDL. Complete CETP inhibition
      did not reduce cholesterol esterification rates but completely blocked the
      delivery of new CE to VLDL, whereas, 50% inhibition of CETP reduced this CE flux
      to VLDL by <20%. Thus, inhibition of CETP by <or=50% preferentially blocks lipid
      transfers involving LDL while largely maintaining lipid flux through HDL. These
      results suggest that a more beneficial therapeutic outcome may be achieved with
      partial, rather than extensive, CETP suppression.

PMID- 16905140
TI  - High chemical reactivity of silver nanoparticles toward hydrochloric acid.
AB  - High chemical reactivity of Ag nanoparticles was observed in the reaction with
      hydrochloric acid: Ag (nanoparticles)+ HCl-->AgCl + H2; the reaction product
      silver chloride was characterized by X-ray powder diffraction to give a direct
      evidence for the reaction which has been proved impossible for the bulk Ag.

PMID- 16905141
TI  - Formation and stability of paraffin oil-in-water nano-emulsions prepared by the
      emulsion inversion point method.
AB  - Paraffin oil-in-water nano-emulsions stabilized by Tween 80/Span 80 were prepared
      using the emulsion inversion point method at different emulsification
      temperatures. Nano-emulsions with droplet size below 200 nm were formed above a
      critical surfactant-to-oil ratio of 0.20 at 50 degrees C. The main
      destabilization mechanism of the systems was found to be Ostwald ripening. An
      interesting phenomenon was that the Ostwald ripening rate declined as the
      surfactant concentration rose. Furthermore, flocculation was also found to
      contribute to the instability of the nano-emulsions, especially for those with
      low surfactant concentrations. Study on the electrophoretic properties of
      emulsion droplets revealed a negative value of the zeta potential, which was
      strongly dependent on the pH of the systems.

PMID- 16905139
TI  - Renal dysfunction increases the risk of saphenous vein graft occlusion: results
      from the Post-CABG trial.
AB  - OBJECTIVES: Saphenous vein grafts are common among patients with a history of
      coronary artery bypass graft (CABG) surgery. Chronic kidney disease (CKD) is an
      established cardiovascular risk factor, but its role in graft disease has not
      been evaluated. METHODS AND RESULTS: The Post-CABG Trial randomized 1351 patients
      who had undergone CABG surgery 1-11 years earlier to high- or low-dose lovastatin
      and to low-dose warfarin or placebo. Coronary angiography was conducted at
      baseline and after a median follow-up time of 4.2 years. Subjects were grouped
      according to their baseline estimated glomerular filtration rate (eGFR). The
      primary trial endpoint was significant graft disease progression assessed
      angiographically. Additional pre-defined endpoints included occlusion of grafts
      patent at baseline, change in minimum lumen diameter, and a composite endpoint of
      recurrent clinical events. Decreasing eGFR was associated with an increased risk
      of graft occlusion (P(trend)=0.040), but not substantial atherosclerotic
      progression (P(trend)=0.30), per-graft change in minimum lumen diameter
      (P(trend)=0.067), or recurrent clinical events (P(trend)=0.86). We did not
      observe significant effect modification of treatment effects by the presence of
      CKD. CONCLUSIONS: CKD may be associated with increased risk of atherosclerotic
      plaque disruption rather than atherosclerotic progression in saphenous vein
      grafts.

PMID- 16905142
TI  - Novel cross-linked enzyme-antibody conjugates for Western blot and ELISA.
AB  - Covalent cross-linking of enzymes to antibodies to produce immunoconjugates for
      Western blot analysis and ELISAs was achieved using in vacuo cross-linking
      methodology [Simons, B.L., King, M.C., Cyr, T., Hefford, M.A., Kaplan, H., 2002.
      Covalent cross-linking of proteins without chemical reagents. Protein Sci. 11,
      1558.]. The advantageous feature of this methodology for producing enzyme
      antibody conjugates is that the cross-linking is accomplished without the use of
      chemical modifying or activating reagents. This reduces the potential activity
      loss due to chemical modification and allows easy recovery of any free antibody
      or native enzyme. In vacuo cross-linking of horseradish peroxidase (HRP) to anti
      rabbit immunoglobulin G (IgG) produced an enzyme-linked antibody with an improved
      sensitivity for antigen detection compared to a commercial conjugate prepared by
      conventional chemical cross-linking methods. A soluble multi-enzyme-based
      immunoconjugate was prepared by the in vacuo cross-linking of HRP to a high
      molecular weight polyglutamic acid polymer followed by the in vacuo cross-linking
      of a limiting amount of antibody to yield an antibody-(HRP)n-polyglutamate
      complex. This complex had a detection signal 100-fold greater than that of the
      1:1 enzyme-antibody conjugates prepared by chemical cross-linking.

PMID- 16905143
TI  - Germinoma in razor clam Ensis arcuatus (Jeffreys, 1865) in Galicia (NW Spain).
AB  - Germinoma is a gonadal neoplasm originating from progenitor cells in germinal
      epithelium. Over the last four decades it has been diagnosed in several species
      of marine bivalve molluscs but most consistently in some populations of
      Mercenaria mercenaria and Mya arenaria in North America. Tissue sections of
      gonads from Ensis arcuatus (family Pharidae--superfamily Solenacea), collected in
      Ria de Vigo (Galicia-NW Spain), revealed germinoma in both males and females.
      Proliferating, undifferentiated, germ cells, with no evidence of maturation, had
      formed discrete masses in the walls and lumens of gonadal follicles. This is the
      first report of germinoma in superfamily Solenacea.

PMID- 16905144
TI  - Experimental transmission and tissue tropism of white spot syndrome virus (WSSV)
      in two species of lobsters, Panulirus homarus and Panulirus ornatus.
AB  - The susceptibility of two species of lobsters, Panulirus homarus and Panulirus
      ornatus to white spot syndrome virus (WSSV) was tested by oral route and
      intramuscular injection. The results revealed that these lobsters were as highly
      susceptible as marine shrimp when the WSSV was administered intramuscularly. The
      WSSV caused 100% mortality in both Panulirus homarus and Panulirus ornatus, at
      168 and 120 h, respectively, after intramuscular injection and failed to cause
      mortality when given orally. The presence of WSSV in moribund lobsters was
      confirmed by single-step and nested PCR, Western blot, histology, and bioassay
      test. It was found in eyestalk, gill, head muscle, tail muscle, hemolymph,
      appendages, and stomach. In lobsters with oral route infection, all tested organs
      except stomach and head muscle was negative for WSSV by nested PCR at 120 h post
      inoculation. The stomach and head muscle was positive by nested PCR at 120 h
      p.i., but negative at 168 h p.i. Western blot analysis was negative in all the
      tested organs of both species of lobster at 120 h post-inoculation by oral route.

PMID- 16905145
TI  - The effect of peritrich ciliates on some freshwater leeches from Assiut, Egypt.
AB  - During October 2004 to April 2005, when water temperature ranged between 18 and
      22 degrees C, over than 500 specimens of leeches namely Alboglossiphonia
      polypompholyx, Batracobdelloides tricarinata, Helobdella conifera
      (Rhynchobdellida), Barbronia assiuti, and Salifa delicata (Arhynchobdellida) were
      collected from Al-Sont canal near Assiut city. About 80% of these specimens were
      infected with the peritrich ciliate Epistylis sp. The infection occurred in the
      field, both rhynchobdellid and arhynchobdellid leeches were infected, but
      Epistylis can infect rhynchobdellids more than arhynchobdellids. Both light and
      scanning electron microscopy showed the morphology of this parasite which
      attached to the surface of the leech body by a stalk. Histopathological studies
      revealed the damage of cuticle, epidermis, and dermis of the leech body wall at
      the area of attachment and the leech body seemed to be sloughy. Presence of this
      parasite in high numbers covering large areas of the body can impede gas exchange
      leading to leech suffocation and finally its death. Like the other sessile single
      celled ciliates Epistylis spp. feed on bacteria and suspended organic debris,
      which are prevalent in nutrient-rich water, hence, Epistylis is a good indicator
      of poor water quality (pollution). The present study represents the first report
      of the effect of Epistylis on leeches collected from Egypt.

PMID- 16905146
TI  - The compatibility of a nucleopolyhedrosis virus control with resistance
      management for Bacillus thuringiensis: co-infection and cross-resistance studies
      with the diamondback moth, Plutella xylostella.
AB  - The use of genetically modified crops expressing Bacillus thuringiensis (Bt)
      toxins can lead to the reduction in application of broad-spectrum pesticides and
      an increased opportunity for supplementary biological control. Bt microbial
      sprays are also used by organic growers or as part of integrated pest management
      programs that rely on the use of natural enemies. In both applications the
      evolution of resistance to Bt toxins is a potential problem. Natural enemies
      (pathogens or insects) acting in combination with toxins can accelerate or
      decelerate the evolution of resistance to Bt. In the present study we
      investigated whether the use of a nucleopolyhedrovirus (AcMNPV) could potentially
      affect the evolution of resistance to the Bt toxin Cry1Ac in Plutella xylostella.
      At low toxin doses there was evidence for antagonistic interactions between
      AcMNPV and Cry1Ac resistant and susceptible insects. However, this antagonism was
      much stronger and more widespread for susceptible larvae; interactions were
      generally not distinguishable from additive for resistant larvae. Selection for
      resistance to Cry1Ac in two populations of P. xylostella with differing
      resistance mechanisms did not produce any correlated changes in resistance to
      AcMNPV. Stronger antagonistic interactions between Bt and AcMNPV on susceptible
      rather than resistant larvae can decrease the relative fitness between Bt
      resistant and susceptible larvae. These interactions and the lack of cross
      resistance between virus and toxin suggest that the use of NPV is compatible with
      resistance management to Bt products.

PMID- 16905147
TI  - Uncoupling of a CLC Cl-/H+ exchange transporter by polyatomic anions.
AB  - CLC-ec1 is a bacterial archetype of CLC transporters, a ubiquitous class of
      proteins that catalyze transmembrane exchange of Cl- and H+ necessary for pH
      regulation of numerous physiological processes. Despite a profusion of high
      resolution structures, the molecular mechanism of exchange remains unknown. Here,
      we rigorously demonstrate strict exchange stoichiometry of 2 Cl-/1 H+. In
      addition to Cl- and Br-, two non-halide ions, NO3- and SCN-, are shown to be
      transported by CLC-ec1, but with reduced H+ counter-transport. The loss of proton
      coupling to these anions is accompanied by an absence of bound anions in the
      central and external Cl- binding sites in the protein's anion selectivity region,
      as revealed by crystallographic comparison of Br- and SeCN- bound to this region.

PMID- 16905148
TI  - A novel haem-binding interface in the 22 kDa haem-binding protein p22HBP.
AB  - The 22 kDa haem-binding protein, p22HBP, is highly expressed in erythropoietic
      tissues and binds to a range of metallo- and non-metalloporphyrin molecules with
      similar affinities, suggesting a role in haem regulation or synthesis. We have
      determined the three-dimensional solution structure of p22HBP and mapped the
      porphyrin-binding site, which comprises a number of loops and a alpha-helix all
      located on a single face of the molecule. The structure of p22HBP is related to
      the bacterial multi-drug resistance protein BmrR, and is the first protein with
      this fold to be identified in eukaryotes. Strikingly, the porphyrin-binding site
      in p22HBP is located in a similar position to the drug-binding site of BmrR.
      These similarities suggest that the broad ligand specificity observed for both
      BmrR and p22HBP may result from a conserved ligand interaction mechanism. Taken
      together, these data suggest that the both the fold and its associated function,
      that of binding to a broad range of small hydrophobic molecules, are ancient, and
      have been adapted throughout evolution for a variety of purposes.

PMID- 16905149
TI  - Structure of the class IV adenylyl cyclase reveals a novel fold.
AB  - The crystal structure of the class IV adenylyl cyclase (AC) from Yersinia pestis
      (Yp) is reported at 1.9 A resolution. The class IV AC fold is distinct from the
      previously described folds for class II and class III ACs. The dimeric AC-IV
      folds into an antiparallel eight-stranded barrel whose connectivity has been seen
      in only three previous structures: yeast RNA triphosphatase and two proteins of
      unknown function from Pyrococcus furiosus and Vibrio parahaemolyticus. Eight
      highly conserved ionic residues E10, E12, K14, R63, K76, K111, D126, and E136 lie
      in the barrel core and form the likely binding sites for substrate and divalent
      cations. A phosphate ion is observed bound to R63, K76, K111, and R113 near the
      center of the conserved cluster. Unlike the AC-II and AC-III active sites that
      utilize two-Asp motifs for cation binding, the AC-IV active site is relatively
      enriched in glutamate and features an ExE motif as its most conserved element.
      Homologs of Y. pestis AC-IV, including human thiamine triphosphatase, span the
      three kingdoms of life and delineate an ancient family of phosphonucleotide
      processing enzymes.

PMID- 16905150
TI  - The human IgE-encoding transcriptome to assess antibody repertoires and
      repertoire evolution.
AB  - Upon encounter with antigen, the B lymphocyte population responds by producing a
      diverse set of antigen-specific antibodies of various isotypes. The vast size of
      the responding populations makes it very difficult to study clonal evolution and
      repertoire composition occurring during these processes in humans. Here, we have
      explored an approach utilizing the H-EPSILON-encoding transcriptome to
      investigate aspects of repertoire diversity during the season of antigen
      exposure. We show through sequencing of randomly picked transcripts that the
      sizes of patients' repertoires are relatively small. This specific aspect of the
      transcriptome allows us to construct evolutionary trees pinpointing features of
      somatic hypermutation as it occurs in humans. Despite the small size of the
      repertoires, they are highly diverse with respect to VDJ gene usage, suggesting
      that the H-EPSILON-encoding transcriptome is a faithful mimic of other class
      switched isotypes. Importantly, it is possible to use antibody library and
      selection technologies to define the specificity of clonotypes identified by
      random sequencing. The small size of the H-EPSILON-encoding transcriptome of
      peripheral blood B cells, the simple identification of clonally related sets of
      genes in this population, and the power of library and selection technologies
      ensure that this approach will allow us to investigate antibody evolution in
      human B lymphocytes of known specificity. As H-EPSILON repertoires show many of
      the hallmarks of repertoires encoding other isotypes, we suggest that studies of
      this type will have an impact on our understanding of human antibody evolution
      even beyond that occurring in the IgE-producing B cell population.

PMID- 16905151
TI  - Arsenate reduction: thiol cascade chemistry with convergent evolution.
AB  - The frequent abundance of arsenic in the environment has guided the evolution of
      enzymes for the reduction of arsenate. The arsenate reductases (ArsC) from
      different sources have unrelated sequences and structural folds, and can be
      divided into different classes on the basis of their structures, reduction
      mechanisms and the locations of catalytic cysteine residues. The thioredoxin
      coupled arsenate reductase class is represented by Staphylococcus aureus pI258
      ArsC and Bacillus subtilis ArsC. The ArsC from Escherichia coli plasmid R773 and
      the eukaryotic ACR2p reductase from Saccharomyces cerevisiae represent two
      distinct glutaredoxin-linked ArsC classes. All are small cytoplasmic redox
      enzymes that reduce arsenate to arsenite by the sequential involvement of three
      different thiolate nucleophiles that function as a redox cascade. In contrast,
      the ArrAB complex is a bacterial heterodimeric periplasmic or a surface-anchored
      arsenate reductase that functions as a terminal electron acceptor and transfers
      electrons from the membrane respiratory chain to arsenate. Finally, the less well
      documented arsenate reductase activity of the monomeric arsenic(III) methylase,
      which is an S-adenosylmethionine (AdoMet)-dependent methyltransferase. After each
      oxidative methylation cycle and before the next methylation step, As(V) is
      reduced to As(III). Methylation by this enzyme is also considered an arsenic
      resistance mechanism for bacteria, fungi and mammals.

PMID- 16905152
TI  - Normal anatomy of the developing fetal brain. Ex vivo anatomical-magnetic
      resonance imaging correlation.
AB  - Fetal brain Magnetic Resonance Imaging (MRI) is a new technique of growing
      interest, with a high potential to detect prenatal central nervous system
      abnormalities. This requires an accurate knowledge of the normal morphological
      sequence of brain development. In this paper we studied the cortical development
      of post-mortem normal fetal brains, correlating MRI estimations of fetal age with
      in vitro anatomical and anthropometric measurements. Ten post-mortem fetal heads
      were submitted to MRI. Maturational state of sulci and gyri and gray-white matter
      differentiation were analysed in the MRIs and by dissection of the brains. The
      findings were correlated with the previously estimated ages of the fetuses, which
      varied between 17 and 38 weeks. Consistency between methods was assessed
      employing intraclass correlation coefficient and Bland-Altman plots, with a 95%
      confidence interval. Estimations of fetal age obtained by MRI were very similar
      to those achieved by anthropometric measurements or by considering anatomical
      parameters. Gyral development proved to be more precise than gray-white matter
      differentiation for this purpose. Fetal MRI proved to be as reliable as the
      macroscopic anatomical examination for depicting normal cortical developmental
      sequence and age, suggesting that this technique may be a suitable option for
      achieving precise information about the morphology of human brains along the
      gestational period.

PMID- 16905153
TI  - The epidemiology of stroke in sickle cell patients in Yaounde, Cameroon.
AB  - BACKGROUND AND PURPOSE: Stroke, a severe and recurrent but preventable
      complication of sickle cell disease (SCD), has not been well studied in Cameroon.
      To obtain baseline data towards the development of a national stroke prevention
      programme in SCD, we studied a sample of sickle cell patients with the aim of
      determining stroke prevalence, clinical presentation and management practices.
      PATIENTS AND METHODS: Homozygous sickle cell patients in two centres in Yaounde
      were screened for stroke, in a cross-sectional study. Stroke was diagnosed
      clinically and confirmed where possible with brain computerized tomography. The
      National Institutes of Health Stroke Score (NIHSS) and modified Rankin scale
      (mRS) were used to assess stroke severity. Management practices were noted from
      patient charts. RESULTS: One hundred and twenty patients aged 7 months to 35
      years (mean age 13.49+/-8.79 years) were included. Eight cases of stroke (mean
      age 16.6+/-11.2 years) were identified, giving a stroke prevalence of 6.67%.
      Cerebral infarction was thrice as common as cerebral hemorrhage and clinical
      presentation was classical. Cerebral infarction was more frequent in patients
      aged below 20 years and hemorrhage in those above 20 (p=0.11). The annual
      recurrence rate was 25%. Missed diagnosis rate by attending physician was 25%.
      The NIHSS and mRS showed high stroke severity. Stroke management practices were
      insufficient and no patient received any form of stroke prophylaxis. CONCLUSION:
      Stroke prevalence and presentation in sickle cell patients in Yaounde is similar
      to that observed in developed countries, but the wide management gap calls for
      rapid action. Our situation is ideal for the study of the natural history of
      stroke in sickle cell disease.

PMID- 16905154
TI  - Mitochondrial tRNA sequences as unusual replication origins: pathogenic
      implications for Homo sapiens.
AB  - The heavy strand of vertebrate mitochondrial genomes accumulates deaminations
      proportionally to the time it spends single-stranded during replication. A
      previous study showed that the strength of genome-wide deamination gradients
      originating from tRNA gene's locations increases with their capacities to form
      secondary structures resembling mitochondrial origins of light strand replication
      (OL), suggesting an alternative function for tRNA sequences. We hypothesize that
      this function is frequently pathogenic for those tRNA genes that normally do not
      form OL-like structures, because this could cause excess mutations in genome
      regions unadapted to tolerate them. In human mitochondrial genomes, pathogenic
      tRNA variants usually form less OL-like structures than non-pathogenic ones in
      cases where the normal non-pathogenic tRNA variant can function as OL, as
      evolutionary analyses reveal. For tRNAs lacking the putative OL-like functioning
      capacity, pathogenic variants form more OL-like secondary structures,
      particularly structures that might invoke bi-directional replication (true for 14
      among 21 tRNA species, p<0.05, sign test; significantly at p<0.05 (1 tailed test)
      for 7 tRNA species), but not more unidirectional replication invoking structures.
      Accounting for the functional cloverleaf-like structure-forming capacities of
      tRNAs yields similar results. Rare, non-pathogenic tRNA mutants tend to form more
      OL-like structures than the common, non-pathogenic ones, suggesting weak
      directional selection also among non-pathogenic variants. The duration spent
      single stranded by a region of the heavy strand (D(ssH)) during replication,
      estimated by integrating over all regions that can function as OL in Homo sapiens
      mitochondrial genomes, increases with distance of that region from the Dloop.
      This suggests convergence of single-strandedness during replication and
      transcription, and explains conserved locations of tRNA species in mitochondrial
      genomes and bacterial operons. These locations minimize deamination costs only in
      anticodons and not in other tRNA regions, during replication and transcription.
      Therefore, putative functioning as OLs by tRNA sequences is normal at some
      locations and pathogenic at others.

PMID- 16905155
TI  - Effects of bisphenol A on thyroid hormone-dependent up-regulation of thyroid
      hormone receptor alpha and beta and down-regulation of retinoid X receptor gamma
      in Xenopus tail culture.
AB  - We investigated effects of different concentrations (10(-7) - 10(-5) M) of
      bisphenol A (BPA), which is known as an estrogenic and anti-thyroid hormonal
      endocrine disrupter, on the expression of thyroid hormone receptor (TR) alpha and
      beta and retinoid X receptor (RXR) gamma mRNA in tails of stage 52-54 Xenopus
      tadpoles in organ culture in the presence or absence of different concentrations
      of triiodo-thyronine (T(3)). In the absence of T(3), BPA at any concentration
      examined did not show remarkable effects on tail length but blocked 10(-7) M T(3)
      induced tail resorption in a concentration-dependent manner. Semi-quantitative
      analyses of TRalpha and TRbeta mRNAs by RT-PCR in the tail specimens indicated
      that BPA shows an apparent antagonistic effect towards the receptors and reduced
      their mRNA levels relative to controls. When administered together with 10(-7) M
      T(3), the antagonistic effects of BPA were detected more clearly and dose
      dependently. While BPA prevented the autoinduction of both TRalpha and TRbeta
      genes by T(3), the effect was less marked on TRalpha than on TRbeta. BPA also
      moderately suppressed RXRgamma gene expression. Gene expression of RXRgamma, a
      partner for heterodimer formation of TRs, was supressed by T(3) alone and also by
      BPA alone, but no additive effects were observed so far as studied. The present
      study indicates that a relatively low concentration of BPA, 10(-7) M, as compared
      with those examined previously (10(-5) to 10(-4) M) by us and other
      investigators, acts as an antagonist of T(3) through suppression of TRalpha and
      TRbeta gene expression in Xenopus tail in culture.

PMID- 16905156
TI  - Heterozygous individuals bearing a founder mutation in the XPA DNA repair gene
      comprise nearly 1% of the Japanese population.
AB  - Individuals who are homozygotes for mutations in DNA repair genes are at high
      risk for cancer. It is not well documented, however, if the heterozygous carriers
      of the mutation are also predisposed to cancer. To address the issue, xeroderma
      pigmentosum (XP) in Japan is an interesting candidate because of three major
      reasons: XP is an autosomal recessive disorder with an enormously elevated risk
      of skin cancer, the frequency of XP patients is higher in Japan than in other
      parts of the world, and more than half of Japanese XP patients are homozygous for
      the same founder mutation in the XPA gene. We screened archival blood samples
      from Japanese individuals who resided in Hiroshima or Nagasaki. A simple PCR-RFLP
      method was developed that is highly specific for detection of XPA heterozygotes
      carrying the founder mutation. We identified nine XPA heterozygotes among 1,020
      individuals screened for a prevalence of 0.88%. This rate, if representative,
      implies that there are about 1 million carriers of the XPA founder mutation in
      the Japanese population. Thus, investigation of their cancer risk may be
      warranted.

PMID- 16905157
TI  - Can individual repair kinetics of UVC-induced DNA damage in human lymphocytes be
      assessed through the comet assay?
AB  - The suitability of the comet assay for quantifying DNA repair capacity at
      individual level was studied following the kinetics of nucleotide excision repair
      (NER) in human lymphocytes from four healthy donors, at various time steps after
      a single dose of UVC. A significant increase of DNA migration was seen as soon as
      20 min after UV exposure, reaching the peak within 60-90 min. Afterwards, a rapid
      decline was observed, approaching the basal level at 180-240 min. The increase
      could be ascribed to excision activity, while the reduction to gap filling and
      rejoining, as demonstrated by the effects of phase-specific inhibitors,
      novobiocin and aphidicolin. Therefore, the comet assay should allow following the
      biphasic kinetics of NER. Wide inter-individual differences were observed,
      although repeated tests on the same donor cells revealed a large experimental
      variation. To quantitatively compare the individual patterns, a mathematical
      model was developed that adequately fitted the experimental results and estimated
      appropriate descriptors for each phase and for each donor. A second approach was
      also used to directly compare the distributions of damaged cells and to assess
      the differences between donors and between experiments visualizing them as
      reciprocal distances on a two-dimensional space computed with a principal
      component analysis (PCA). The results confirmed the inter-individual differences,
      but also the strong influence of experimental factors of the comet assay. The two
      approaches provided the means of accurately comparing DNA repair kinetics at
      individual level, taking also into account the experimental variability which
      poses serious doubts on the suitability of the comet assay. Nevertheless, since
      this methodology allows a detailed analysis of repair kinetics and it is
      potentially very useful for identifying individual with reduced repair capacity,
      further efforts have to be addressed to improve the reproducibility of the comet
      assay.

PMID- 16905158
TI  - The mutagenicity of urban particulate matter in an enzyme free system is
      associated with the generation of reactive oxygen species.
AB  - Urban particulate matter (UPM) contributes to lung cancer incidence. UPM has been
      shown to be genotoxic to mammalian cells and to induce mutations in the Ames
      assay. Here, we have studied the induction of mutations generated by direct
      acting mutagenic components of UPM, using the supF forward mutation assay.
      Plasmid pSP189 was exposed to UPM in aqueous solution in the presence of sucrose
      buffer, to reduce strand breaks. The mutation frequency induced by 1
      microg/microl UPM was 4.99 mutants per 10(4) colonies. This was reduced to 0.84
      and 1.48 mutants per 10(4) colonies by addition of mannitol (1 mM) or EDTA (1
      mM), respectively. A large percentage of mutant plasmids contained frameshift
      mutations (57%), and 31% of mutant plasmids contained multiple mutations. Of the
      base substitution mutations, 88% were at GC pairs, with twice as many
      transversions as transitions. The types of mutations induced, the reduction of
      mutagenicity by the inclusion of the free radical scavenger, mannitol, or the
      metal chelator, EDTA, and the sequence context of the induced mutations all
      support the conclusion that the majority of mutations were induced by reactive
      oxygen species generated by metal ions present in the UPM. Most mutation studies
      with UPM have focused on organic carcinogens present on UPM. Our results
      highlight the potential contribution of metal ions to the mutagenicity of UPM.

PMID- 16905159
TI  - Parallel regulation by olanzapine of the patterns of expression of 5-HT2A and D3
      receptors in rat central nervous system and blood cells.
AB  - Patterns of protein expression can be used to identify biomarkers of disease,
      prognosis or treatment response. Peripheral 5-HT2A and D3 receptors have been
      proposed as protein markers in schizophrenia. We investigated the possible
      parallel regulation of these candidate biomarkers in central nervous system (CNS)
      and peripheral blood cells by a comparative study of the effects of antipsychotic
      treatment on the expression of the receptors in both systems in rats. Acute (24
      and 48 h) and subchronic (16 days) treatment of rats with olanzapine induced a
      significant decrease in 5-HT2A receptor density both in frontal cortex
      (Bmax=76.2%, 83.0% and 46.0% of control after 24 h, 48 h and 16 days of
      treatment, respectively; P<0.01) and blood platelets (Bmax approximately 55% of
      control at all times measured; P<0.01), without any changes in receptor affinity.
      Furthermore, olanzapine induced redistribution in 5-HT2A-like immunoreactivity
      and time-dependent remodelling of synaptic circuits involved in the activity of
      pyramidal and GABAergic neurons in frontoparietal motor cortex of treated rats,
      as assessed by immunohistochemical studies. D3 receptor mRNA levels increased
      significantly by 52.5% (P<0.01) and 21.1% (P<0.05) in nucleus accumbens, and by
      53.4% (P<0.05) and 91.7% (P<0.01) in lymphocytes, after acute (24 h and 48 h)
      treatment with olanzapine, returning to levels similar to control after
      subchronic treatment (16 days). In conclusion, we observed in rats after
      olanzapine treatment: (1) parallelism in the regulation of 5-HT2A receptors in
      frontal cortex and in blood platelets; (2) parallelism in the regulation of D3
      mRNA levels in nucleus accumbens and lymphocytes. These results endorse the
      interest in future studies aimed at validating these receptors as candidate
      biomarkers in schizophrenia.

PMID- 16905160
TI  - The role of group I metabotropic glutamate receptors in acquisition and
      expression of contextual and auditory fear conditioning in rats - a comparison.
AB  - Glutamatergic neurotransmission in the CNS plays a predominant role in learning
      and memory. While NMDA receptors have been extensively studied, less is known
      about the involvement of group I metabotropic glutamate receptors in this area.
      The purpose of the present study was to evaluate the contribution of mGluR1 and
      mGluR5 to both acquisition and expression of behaviours in contextual and
      auditory fear conditioning models. The effects of both receptor types were tested
      using selective antagonists: (3-ethyl-2-methyl-quinolin-6-yl)-(4-methoxy
      cyclohexyl)-methanone methanesulfonate (EMQMCM) for mGluR1, and [(2-methyl-1,3
      thiazol-4-yl)ethynyl]pyridine (MTEP) for mGluR5. Their effects on acquisition
      were compared to those of the NMDA receptor antagonist (+)MK-801, and the
      unselective muscarinic antagonist scopolamine, while diazepam and citalopram
      served as reference compounds in the expression experiments. EMQMCM (1.25 to
      5mg/kg) impaired acquisition of contextual fear conditioning (CFC), but not
      auditory fear conditioning (AFC). Similarly, administration of MTEP during the
      acquisition phase impaired learning in CFC at doses of 2.5 to 10mg/kg, but was
      ineffective in AFC. When given before the retention test, both EMQMCM (1 and
      3mg/kg) and MTEP (3mg/kg) impaired expression of CFC. In contrast, MTEP (2.5 and
      5mg/kg) blocked the expression of AFC, while EMQMCM was ineffective. In
      conclusion, group I mGlu receptors are shown to be involved in the acquisition of
      hippocampus-dependent CFC, but not hippocampus-independent AFC. Unlike mGluR5,
      mGluR1 does not seem be involved in expression of AFC.

PMID- 16905161
TI  - Priming of long-term potentiation mediated by ryanodine receptor activation in
      rat hippocampal slices.
AB  - Administration of the Group 1 metabotropic glutamate receptor (mGluR) agonist
      (R,S)-3,5-dihydroxyphenylglycine (DHPG) facilitates ("primes") subsequent long
      term potentiation (LTP) through a phospholipase C signaling cascade that may
      involve release of Ca2+ from the endoplasmic reticulum (ER). We investigated the
      intracellular calcium pathways involved in this priming effect, recording field
      potentials from area CA1 of rat hippocampal slices before and after high
      frequency stimulation. The priming of LTP by DHPG was prevented by co
      administration of cyclopiazonic acid, which depletes ER Ca2+ stores. The priming
      effect was also blocked by the ryanodine receptor (RYR) antagonist ryanodine
      (RYA, 100 microM). In contrast, a low dose of RYA (10 microM) which opens the RYR
      channel, by itself primed LTP. In addition to RYR activation, entry of
      extracellular calcium through store-operated channels appears necessary for
      priming, since diverse treatments known to impede store-operated channel activity
      completely blocked both RYA and DHPG priming effects. Thus, RYR activation plays
      a critical role in the priming of LTP by Group 1 mGluRs, and this effect is
      coupled to the entry of extracellular calcium, probably through store-operated
      calcium channels.

PMID- 16905163
TI  - Behavioural and physiological responses of dogs entering re-homing kennels.
AB  - Behaviour and urinary cortisol/creatinine ratios (C/C) were monitored in twenty
      six dogs, on days 1, 2, 3, 5, 7 and 10 following their admission to a rehoming
      kennel. Half had been relinquished from homes, and half were either strays or
      returns to the shelter. Drinking and grooming increased with time, while panting
      and paw-lifting decreased, but only drinking was linked with C/C; dogs observed
      drinking on the first day had significantly lower C/C than dogs not observed
      drinking. Mean molar C/C (40 x 10(-6)+/-16 x 10(-6)) tended to decrease with time
      in the strays and returns, and to increase in dogs relinquished from homes,
      although C/C on the first day was highly variable and not distinguishable between
      these two groups. This implies that these populations differed in their long
      term, but possibly not their short-term, responses to kennelling. Dogs with
      rising C/C were more active on average than those with falling C/C, but the
      opposite trend was detected when making comparisons within-dog. The relationship
      between C/C and exercise is therefore complex and warrants further investigation
      before C/C can be considered as a reliable indicator of welfare in this species.

PMID- 16905162
TI  - False recognition of incidentally learned pictures and words in primary
      progressive aphasia.
AB  - Recognition memory was tested in patients with primary progressive aphasia (PPA),
      a language based dementia with relative preservation of memory for at least the
      first 2 years. The goal of the study was two-fold: (1) to compare true and false
      recognition rates for words versus pictures in patients with PPA and cognitively
      intact controls and (2) to determine if the semantic relatedness of distracters
      to-targets influences recognition memory performance. Overall, performance of PPA
      patients was worse for words than pictures. PPA patients and healthy elderly
      controls showed similar recognition rates for studied items. However, the
      patients had significantly more false alarms than controls, particularly to
      semantically related items. This suggests that the aphasia in PPA patients
      contributes to their difficulty in selecting among items within a semantic class.

PMID- 16905164
TI  - Pinus taeda phenylpropenal double-bond reductase: purification, cDNA cloning,
      heterologous expression in Escherichia coli, and subcellular localization in P.
      taeda.
AB  - A phenylpropenal double-bond reductase (PPDBR) was obtained from cell suspension
      cultures of loblolly pine (Pinus taeda L.). Following trypsin digestion and amino
      acid sequencing, the cDNA encoding this protein was subsequently cloned, with the
      functional recombinant protein expressed in Escherichia coli and characterized.
      PPDBR readily converted both dehydrodiconiferyl and coniferyl aldehydes into
      dihydrodehydrodiconiferyl and dihydroconiferyl aldehydes, when NADPH was added as
      cofactor. However, it was unable to reduce directly either the double bond of
      dehydrodiconiferyl or coniferyl alcohols in the presence of NADPH. During this
      reductive step, the corresponding 4-proR hydrogen was abstracted from [4R-3H]
      NADPH during hydride transfer. This is thus the first report of a double-bond
      reductase involved in phenylpropanoid metabolism, and which is presumed to be
      involved in plant defense. In situ mRNA hybridization indicated that the PPDBR
      transcripts in P. taeda stem sections were localized to the vascular cambium, as
      well as to radial and axial parenchyma cell types. Additionally, using P. taeda
      cell suspension culture crude protein extracts, dehydrodiconiferyl and coniferyl
      alcohols could be dehydrogenated to afford dehydrodiconiferyl and coniferyl
      aldehydes. Furthermore, these same extracts were able to convert
      dihydrodehydrodiconiferyl and dihydroconiferyl aldehydes into the corresponding
      alcohols. Taken together, these results indicate that in the crude extracts
      dehydrodiconiferyl and coniferyl alcohols can be converted to
      dihydrodehydrodiconiferyl and dihydroconiferyl alcohols through a three-step
      process, i.e. by initial phenylpropenol oxidation, then sequential PPDBR and
      phenylpropanal reductions, respectively.

PMID- 16905165
TI  - Ganoderma - a therapeutic fungal biofactory.
AB  - Ganoderma is a basidiomycete white rot fungus which has been used for medicinal
      purposes for centuries particularly in China, Japan and Korea. A great deal of
      work has been carried out on Ganoderma lucidum. The common names for preparations
      include Lingzhi, Munnertake, Sachitake, Reishi and Youngzhi. This review collates
      the publications detailing activities and compounds by representative species
      whilst considering the most valid claims of effectiveness. The biological
      activities reported of preparations from Ganoderma are remarkable and given most
      emphasis herein as distinct from structure/activity information. The metabolites
      consist of mainly polysaccharides and terpenoids. Many are activities against the
      major diseases of our time and so the present review is of great importance. The
      list of effects is huge ranging from anti-cancer to relieving blockages of the
      bladder. However, the reports have not all been tested scientifically with the
      convincing evidence is reserved for assays of pure compounds. It is a prime
      example of an ancient remedy being of great relevance to the modern era. There
      does appear to be an assumption that the therapeutic effects attributed to the
      fungus have been proven. The next step is to produce some effective medicines
      which may be hampered by problems of mass production.

PMID- 16905166
TI  - Mortality from epilepsy in an onchocerciasis-endemic area in West Uganda.
AB  - Mortality from epilepsy was investigated in a rural area of West Uganda where
      epilepsy is found to be closely linked to onchocerciasis. Thirty-three female and
      28 male patients (age range 4-58 years, median 15 years) were identified in a
      population-wide prevalence survey and were followed from June 1994 to March 2001
      (observation period 3,929 person-months). Patients had continuing access to
      antiepileptic drug (AED) treatment with phenobarbital. Eighteen patients died
      during the period of observation, corresponding to a standardised mortality ratio
      (SMR) of 7.2 (95% CI 4.4-11.6; P<0.0001). Adherence to treatment was considered
      good in 36 of 56 patients receiving regular AEDs, with a SMR of 7.4 in this group
      compared with a SMR of 8.0 for those 20 patients considered poorly adherent.
      These findings show high mortality in patients with onchocerciasis-associated
      epilepsy despite regular AED treatment. Epilepsy appears to have a dramatic
      impact on this community with high Onchocerca volvulus infestation. If the
      suspected causal relationship between epilepsy and infection with O. volvulus
      could be confirmed, this would further underline the importance of sustained
      control efforts against onchocerciasis.

PMID- 16905167
TI  - The role of transmissible diseases in the Holling-Tanner predator-prey model.
AB  - Transmissible diseases are known to induce remarkable major behavioral changes in
      predator-prey systems. However, little attention has been paid to model such
      situations. The latter would allow to predict useful applications in both
      dynamics and control. Here the Holling-Tanner model is revisited to account for
      the influence of a transmissible disease, under the assumption that it spreads
      among the prey species only. We have found the equilibria and analyzed the
      behavior of the system around each one of them. A threshold result determining
      when the disease dies out has been identified. We also investigated the
      parametric space under which the system enters into Hopf and transcritical
      bifurcations, around the disease free equilibrium. The system is shown to
      experience neither saddle-node nor pitch-fork bifurcation. Global stability
      results are obtained by constructing suitable Lyapunov functions.

PMID- 16905168
TI  - Isolation and cDNA cloning of a potassium channel peptide toxin from the sea
      anemone Anemonia erythraea.
AB  - A potassium channel peptide toxin (AETX K) was isolated from the sea anemone
      Anemonia erythraea by gel filtration on Sephadex G-50, reverse-phase HPLC on
      TSKgel ODS-120T and anion-exchange HPLC on Mono Q. AETX K inhibited the binding
      of (125)I-alpha-dendrotoxin to rat synaptosomal membranes, although much less
      potently than alpha-dendrotoxin. Based on the determined N-terminal amino acid
      sequence, the nucleotide sequence of the full-length cDNA (609bp) encoding AETX K
      was elucidated by a combination of degenerate RT-PCR, 3'RACE and 5'RACE. The
      precursor protein of AETX K is composed of a signal peptide (22 residues), a
      propart (27 residues) ended with a pair of basic residues (Lys-Arg) and a mature
      peptide (34 residues). AETX K is the sixth member of the type 1 potassium channel
      toxins from sea anemones, showing especially high sequence identities with HmK
      from Heteractis magnifica and ShK from Stichodactyla helianthus. It has six Cys
      residues at the same position as the known type 1 toxins. In addition, the dyad
      comprising Lys and Tyr, which is considered to be essential for the binding of
      the known type 1 toxins to potassium channels, is also conserved in AETX K.

PMID- 16905169
TI  - Bothrops jararaca venom gland transcriptome: analysis of the gene expression
      pattern.
AB  - Bothrops jararaca is a pit viper responsible for the majority of snake envenoming
      accidents in Brazil. As an attempt to describe the transcriptional activity of
      the venom gland, ESTs of a cDNA library constructed from B. jararaca venom gland
      were generated and submitted to bioinformatics analysis. The results showed a
      clear predominance of transcripts coding for toxins instead of transcripts coding
      for proteins involved in cellular functions. Among toxins, the most frequent
      transcripts were from metalloproteinases (52.6%), followed by serine-proteinases
      (28.5%), C-type lectins (8.3%) and bradykinin-potentiating peptides (BPPs)
      (6.2%). Results were similar to that obtained from the transcriptome analysis of
      B. insularis, a phylogenetically close sister of B. jararaca, though some
      differences were observed and are pointed out, such as a higher amount of the
      hypotensive BPPs in B. insularis transcriptome (19.7%). Another striking
      difference observed is that PIII and PII-classes of metalloproteinases are
      similarly represented in B. jararaca in contrast to B. insularis, in which a
      predominance of PIII-class metalloproteinase, which present a more intense
      hemorrhagic action, is observed. These features may, in part, explain the higher
      potency of B. insularis venom. The results obtained can help in proteome studies,
      and the clones can be used to directly probe the genetic material from other
      snake species or to investigate differences in gene expression pattern in
      response to factors such as diet, aging and geographic localization.

PMID- 16905170
TI  - CpG methylation of HPV 16 LCR at E2 binding site proximal to P97 is associated
      with cervical cancer in presence of intact E2.
AB  - Human papillomavirus type 16 (HPV-16) E2 protein negatively regulates
      transcription of the E6 and E7 genes. This study was done to test the hypothesis
      that methylation of the HPV 16 long control region (LCR) is overrepresented among
      cervical cancer (CaCx) cases compared to cytologically normal controls harboring
      intact E2 gene. Methylation of the E2 binding site (E2BS-I), proximal to the P97
      promoter, was assessed by HpaII/ MspI restriction digestion while McrBC digestion
      was used to assess LCR-E6 (7289-540) for 57 CaCx samples and 15 normal controls.
      E2BS-I methylation was found to be significantly higher (56.14%) in cases
      compared to (20%) controls [OR(age-adjusted) (95% CI): 4.53 (1.05-19.43)
      p=0.042]. The difference between cases (54.39%) and controls (40%) with respect
      to LCR-E6 methylation status [OR(age-adjusted) (95% CI): 1.77(0.5-6.3); p=0.38]
      was not significant. Sequencing of a randomly selected set of 13 methylated
      malignant samples revealed absence or rare presence, of methylation at CpGs 7579,
      7535, 7683 and 7862 respectively. Methylation was found to be more at CpGs within
      E2 binding sites proximal to the P97 promoter. These results indicate the
      involvement of E2 binding site methylation in presence of intact E2, leading to
      loss of E2 repressor activity in CaCx.

PMID- 16905171
TI  - The effect of the membrane-proximal tyrosine-based sorting signal of HIV-1 gp41
      on viral infectivity depends on sequences within gp120.
AB  - The cytoplasmic domain of the HIV-1 Env glycoprotein (gp41) contains sequences
      that affect the trafficking of Env within the host cell. We previously showed
      that the membrane-proximal tyrosine-based adaptor protein (AP)-binding signal of
      gp41 (Y712XXL) is required for optimal viral infectivity and entry into target
      cells. Because these effects were not attributable to an effect on the
      incorporation of Env into virions, we hypothesized that they involved targeting
      of viral assembly to specific endosomal membranes that conferred greater
      fusogenicity. To further elaborate this hypothesis, we mutated the C-terminal
      leucine-based AP-binding signal of gp41 (LL855/856). In contrast to Env Y712, the
      leucine signal was dispensable for viral infectivity in both single cycle assays
      and during spreading infections within cultures of peripheral blood mononuclear
      cells (PBMCs). To test the hypothesis that these AP-binding motifs target Env to
      endosomes during viral morphogenesis, we compared the subcellular localization of
      wild-type Env to mutants of the Y712 and LL855/856 signals. The results failed to
      support the hypothesis that these signals target viral assembly to specific
      endosomal membranes. Strikingly, in the context of a C2-V3 region that confers
      macrophage-tropism, mutation of Y712 no longer markedly affected viral
      infectivity in either single cycle assays or during spreading infection within
      PBMCs, and it did not impair viral entry. These data indicate that the importance
      of the tyrosine-based sorting signal in gp41 for optimal viral infectivity
      depends on sequences in gp120. This observation is consistent with the hypothesis
      that the Y712 residue is part of the ectodomain of gp41 in virion-associated Env.
      We speculate that as part of the ectodomain, Y712 could affect specifically the
      conformation of the more positively charged CXCR4-tropic V3 loop in a manner that
      augments viral fusogenicity and infectivity.

PMID- 16905172
TI  - Transient low pH treatment enhances infection of lentiviral vector pseudotypes
      with a targeting Sindbis envelope.
AB  - Efficient transduction of primary hematopoietic cell types by oncoretroviral
      vectors and lentiviral vectors with a variety of different envelope pseudotypes
      has proven to be difficult. We recently developed a lentiviral vector based upon
      a modified Sindbis virus envelope that allows targeted transduction via antibody
      recognition to specific cells in unfractionated cell populations. However,
      similar to other envelope pseudotypes, the utility of this vector for some
      primary hematopoietic cells was limited by low transduction efficiencies. Here,
      we report that transient treatment of cells with low pH culture medium
      immediately following infection results in marked enhancements in transduction
      efficiency for primary hematopoietic cells. In combination with antibody directed
      targeting, this simple technique expands the utility of targeting transduction to
      specific cells in mixed populations of primary cells.

PMID- 16905173
TI  - Evaluation of the production, composition and aluminum and iron complexation of
      algogenic organic matter.
AB  - This paper aims at the characterization of algogenic organic matter (AOM)
      produced by the cyanobacteria Anabaena flos-aqua and Microcystis aeruginosa and
      the green algae Scenedesmus quadricauda. Further, it is focused on the
      description of differences in the composition of extracellular organic matter
      (EOM) and intracellular organic matter (IOM), and on the demonstration of AOM
      affinity to aluminum and iron coagulants. The results from the conducted analyses
      imply a significant difference in the amount and properties of the proteins
      contained in EOM in comparison to IOM. The differences in the production of
      proteins also depend on the species of microorganism observed and its growth
      phase; ageing of the culture is accompanied by a gradual increase of the portion
      of proteins forming AOM. Using affinity chromatography (AC), the proteins with
      relative molecular weight around 60 kDa were isolated as a component of AOM of
      cyanobacteria A. flos-aqua and M. aeruginosa. These proteins are able to form
      complex compounds with iron and aluminum.

PMID- 16905174
TI  - Investigation of the mechanism of chlorination of glyphosate and glycine in
      water.
AB  - The chlorination reactions of glyphosate and glycine in water were thoroughly
      studied. Utilizing isotopically enriched (13C and 15N) samples of glycine and
      glyphosate and 1H, 13C, 31P, and 15N NMR spectroscopy we were able to identify
      all significant terminal chlorination products of glycine and glyphosate, and
      show that glyphosate degradation closely parallels that of glycine. We have
      determined that the C1 carboxylic acid carbon of glycine/glyphosate is
      quantitatively converted to CO2 upon chlorination. The C2 methylene carbon of
      glycine/glyphosate is converted to CO2 and methanediol. The relative abundance of
      these two products is a function of the pH of the chlorination reactions. Under
      near neutral to basic reaction conditions (pH 6-9), CO2 is the predominant
      product, whereas, under acidic reaction conditions (pH < 6) the formation of
      methanediol is favored. The C3 phosphonomethylene carbon of glyphosate is
      quantitatively converted to methanediol under all conditions tested. The nitrogen
      atom of glycine/glyphosate is transformed into nitrogen gas and nitrate, and the
      phosphorus moiety of glyphosate produces phosphoric acid upon chlorination. In
      addition to these terminal chlorination products, a number of labile
      intermediates were also identified including N-chloromethanimine, N
      chloroaminomethanol, and cyanogen chloride. The chlorination products identified
      in this study are not unique to glyphosate and are similar to those expected from
      chlorination of amino acids, proteins, peptides, and many other natural organic
      matters present in drinking water.

PMID- 16905175
TI  - Adsorption of p-nitrophenol on activated carbon fixed-bed.
AB  - Carbon fixed-beds are usually used to remove organic contaminants. Adsorption in
      a carbon filter is a dynamic, non-steady process which is not yet completely
      understood. The objective of this paper is to establish a methodology to simplify
      the study of this process based on the wave theory, rapid small-scale column test
      and experimental design/surface response analysis. The constant pattern wave
      hypothesis was confirmed by the experimental data. The influence of the inlet
      concentration of p-nitrophenol and the flow rate on dynamic adsorption was
      studied at 20 degrees C following a central composite design using a second-order
      model. Both parameters have an important influence on the response variables
      studied. The methodology used is a useful tool for studying the dynamic process
      and shows interactions that are difficult to verify by the classical step-by-step
      method.

PMID- 16905176
TI  - Potential contribution of arbuscular mycorrhiza to cadmium immobilisation in
      soil.
AB  - The contribution of arbuscular mycorrhiza (AM) to immobilisation of Cd in
      substrate was studied in two experiments. In the first experiment, substrates
      prepared by cultivating tobacco, either non-mycorrhizal or inoculated with the AM
      fungus Glomus intraradices were enriched with a range of Cd concentrations, and
      Cd toxicity in the substrates was assessed using root growth tests with lettuce
      as a test plant. The tests revealed lower Cd toxicity in the mycorrhizal than in
      the non-mycorrhizal substrate, and the difference increased with increasing total
      Cd concentration in the substrates. In the second experiment, extraradical
      mycelium (ERM) of G. intraradices exposed in vivo to Cd was collected and
      analysed on Cd concentration. The ERM accumulated 10-20 times more Cd per unit of
      biomass than tobacco roots. While Cd concentrations were lower in the biomass of
      mycorrhizal plants than of non-mycorrhizal plants, Cd immobilisation by ERM did
      not affect the total Cd content in mycorrhizal tobacco. It is concluded that
      mycorrhiza may decrease Cd toxicity to plants by enhancing Cd immobilisation in
      soil. The results therefore suggest a potential role of AM symbiosis in the
      phytostabilisation of contaminated soils, where high Cd availability inhibits
      plant growth.

PMID- 16905177
TI  - Solid phase microextraction applied to the analysis of organophosphorus
      insecticides in fruits.
AB  - Trace amounts of organophosphorus pesticides (OPs) were determined in various
      fruits by headspace solid phase microextraction (HS-SPME) and gas chromatography
      nitrogen phosphorous detection (GC-NPD). Sampling from the headspace enhanced
      method selectivity, whereas at the same time improved fiber life time and method
      sensitivity. Diazinon, parathion, methyl parathion, malathion and fenithrothion
      were determined in various fruits: more than 150 samples of 21 types of fruits
      were studied. SPME-GC-NPD provided a useful and very efficient analytical tool:
      method linearity ranged from 1.2 to 700 ng/ml. Limits of detection (LODs) and
      quantitation (LOQs) ranged from 0.03 to 3 ng/ml and 0.12 to 10 ng/ml
      respectively, values well below the residue limits set by the EU. Less than 2% of
      the samples were found positive containing amounts higher than the EU limits. The
      effect of fruit peeling and washing was also investigated.

PMID- 16905178
TI  - A comparison of cortical elastic properties in the craniofacial skeletons of
      three primate species and its relevance to the study of human evolution.
AB  - When a force is applied to an object, the resulting pattern of strain is a
      function of both the object's geometry and its elastic properties. Thus,
      knowledge of elastic properties in craniofacial cortical bone is indispensable
      for exploring the biomechanics and adaptation of primate skulls. However, elastic
      properties, such as density and stiffness, cannot be measured in all species,
      particularly extinct species known only from fossils. In order for advanced
      engineering techniques such as finite element analysis (FEA) to be applied to
      questions of primate and hominid craniofacial functional morphology, it is
      important to understand interspecific patterns of variation in elastic
      properties. We hypothesized that closely related species would have similar
      patterns of bone elastic properties, and that similarities with extant species
      should allow reasonable predictions of elastic properties in the skeletons of
      extinct primate species. In this study, we tested this hypothesis by measuring
      elastic properties in five areas of the external cortex of the baboon
      craniofacial skeleton using an ultrasonic technique, and by comparing the results
      to existing data from macaque and human crania. Results showed that cortical
      density, thickness, elastic and shear moduli, and anisotropy varied among areas
      in the baboon cranium. Similar variation had previously been found in rhesus and
      human crania, suggesting area-specific elastic patterns in the skulls of each
      species. Comparison among species showed differences, suggesting species-specific
      patterns. These patterns were more similar between macaques and baboons for
      density, maximum elastic and shear stiffness, and anisotropy than between either
      of these and humans. This finding demonstrates that patterns of cortical elastic
      properties are generally similar in closely related primate species with similar
      craniofacial morphology. Thus, reasonable estimates of cortical bone elastic
      properties should be possible for extinct species through the study of
      phylogenetically related and functionally similar modern forms. For example,
      reasonable elastic property estimates of cortical bone from fossil hominid skulls
      should be possible once adequate information about such properties in extant
      great apes is added to our current data from humans, macaques, and baboons. Such
      data should eventually allow FEA of craniofacial function in fossil hominids.

PMID- 16905179
TI  - Ultraviolet influence on catalase activity and mineral content in eyeballs of
      gibel carp (Carassius auratus gibelio).
AB  - UV radiation present in the environment may induce several eye disorders
      including inflammation and cataract. The aim of this work was to study catalase
      activity and Mg, Cu, Ca and Zn contents in the eyeballs of gibel carp exposed to
      ecologically relevant doses of UV radiation (0.09 kJ/m2 for UV-A and 0.98 kJ/m2
      for UV-B) simulated in laboratory conditions. Ultraviolet exposure resulted in
      significant reduction of catalase activity in the eyeballs of tested fish.
      Reductions in Mg, Cu and Ca contents after UV exposure were also observed. The
      differences in Mg and Cu levels between control and UV exposed animals were
      statistically significant, whereas the reduction of Ca level was insignificant.
      Zinc level in the eyeballs of UV-exposed fish was significantly higher than in
      non-irradiated specimens. The results suggest that ultraviolet radiation affects
      prooxidant/antioxidant balance and Mg, Cu, Zn contents in the eyes of fish living
      in shallow habitats. These may lead to cataract formation.

PMID- 16905180
TI  - Low PAI-1 activity in relation to the risk for perioperative bleeding
      complications in transurethral resection of the prostate.
AB  - INTRODUCTION: Low levels of plasminogen activator inhibitor type 1 (PAI-1) have
      been associated with increased risk for perioperative bleeding in some case
      reports. The aim of this study was to investigate prospectively whether low PAI-1
      activity increases the risk for perioperative bleeding in patients undergoing
      transurethral resection of prostate, an organ with high fibrinolytic activity.
      PATIENTS AND METHODS: 62 patients with benign prostatic hyperplasia planned for
      transurethral resection were included. Blood samples for PAI-1 were taken
      together with other routine preoperative blood samples 1week before surgery but
      analyzed after the hospitalization. The intraoperative blood loss was determined
      by measuring the amount of hemoglobin in the irrigating fluid. The postoperative
      blood loss was estimated from calculations of hemoglobin mass (Hb mass), which is
      a product of hemoglobin concentration and blood volume. Hb mass was calculated
      before surgery and on the day of discharge, and was adjusted for intraoperative
      blood loss and transfused Hb mass. Bleeding complications were defined as re
      operation due to bleeding, more than 40ml intraoperative bleeding/g resected
      prostatic tissue or postoperative blood loss corresponding to more than 100g of
      hemoglobin. RESULTS: Bleeding complications were observed in 3 of 4 (75%)
      patients with low PAI-1 levels, defined as <1U/ml, and in 16 of 58 (28%) patients
      with PAI-1 levels >1U/ml (P=0.082). After adjustment for resection time, resected
      prostatic mass and systolic blood pressure this became borderline significant
      (odds ratio 11.8; 95% confidence interval 1.00-139; P=0.05). CONCLUSION: Low PAI
      1 activity may contribute to the risk of bleeding after transurethral resection
      of the prostate.

PMID- 16905181
TI  - Cardiovascular prevention in the Hartslag Limburg project: effects of a high-risk
      approach on behavioral risk factors in a general practice population.
AB  - BACKGROUND: This study describes a general-practice-based high-risk
      cardiovascular prevention approach in Maastricht, The Netherlands (1999-2003).
      The intervention consisted of a complete registration of risk factors,
      optimization of medical treatment and health counseling on high fat consumption,
      smoking and physical inactivity. METHODS: Behavioral effects were assessed in a
      trial, randomization by practice and usual care as control. Validated
      questionnaires were completed by 1300 patients at baseline, 1174 after 4 months
      (90.3%) and 1046 (80.5%) after 18 months. RESULTS: After 4 months, intention-to
      treat analyses revealed a decrease in saturated fat intake of 1.3 points (scale
      ranging from 7 to 30 points, p=0.000). This was partly sustained after 18 months
      (-0.5 points, p=0.014). After 18 months, obese intervention patients were more
      likely to be sufficiently physically active than their control counterparts
      (OR=1.90, p=0.023). No intervention effects were found for smoking. CONCLUSION:
      Given the multiple factor and multiple component high-risk approach, the
      intervention had modest effects on only some of the behavioral risk factors
      addressed. Process data showed that the registration of risk factors and the
      optimization of medical treatment were only partly implemented, that the health
      counseling component could be further improved and that the intervention could
      benefit from additional health promoting strategies.

PMID- 16905183
TI  - The generation of germline transgenic silkworms for the production of
      biologically active recombinant fusion proteins of fibroin and human basic
      fibroblast growth factor.
AB  - We generated germline transgenic silkworms bearing a fibroin light chain (FL)
      promoter-driven FL gene whose 3'-end was flanked with human basic fibroblast
      growth factor (bFGF) gene, FL/bFGF gene. The cocoons from transgenic worms were
      trypsinized to remove sericin layers, and treated with solution containing
      CaCl(2), ethanol, and water at a molar ratio of 1:2:8 (CaCl(2)/ethanol/water) to
      solubilize fibroin layers. Western blot analysis showed that the recombinant
      protein, r(FL/bFGF), was solubilized with CaCl(2)/ethanol/water, but not with
      trypsin, indicating that r(FL/bFGF) was in fibroin layers. Thus, it was concluded
      that the worms spun cocoons whose fibroin layers were composed of the inherent
      gene-derived natural fibroin (nF) and r(FL/bFGF). The mixture of nF and
      r(FL/bFGF) was dubbed r(FL/bFGF)nF. The solubilized r(FL/bFGF)nF was refolded
      using the glutathione redox system. Human umbilical vein endothelial cells
      (HUVECs) grew in the refolded r(FL/bFGF)nF-containing culture media, showing that
      bFGF in r(FL/bFGF) was biologically active. r(FL/bFGF)nF immobilized on a culture
      dish also supported the growth of HUVECs in bFGF-free media, suggesting the
      usefulness of r(FL/bFGF)nF as a new biomaterial for tissue engineering. The
      currently developed transgenic silkworms will be suitable for mass production of
      fibroins bearing a variety of biological activities.

PMID- 16905182
TI  - Utilization of frozen-thawed epididymal ram semen to preserve genetic diversity
      in Scrapie susceptible sheep breeds.
AB  - The European Union has introduced transmissible spongiform encephalopathy (TSE)
      resistance breeding programmes for several sheep breeds to cope with the genetic
      susceptibility to Scrapie infections. Due to the different allele frequencies
      among breeds, strong selection for ARR alleles is associated with a loss of
      genetic diversity in small populations and in larger populations with
      unfavourable ARR allele frequencies. To ensure maintenance of genetic diversity,
      an adhoc cryopreservation programme was initiated employing epididymal sperm from
      109 rams representing 16 different breeds within one breeding season. Epididymal
      semen was chosen for this adhoc programme because time consuming training of rams
      for ejaculated semen collection via an artificial vagina was not possible. Prior
      to freezing, average sperm motility was 79.7% and acrosome integrity was 93.7%.
      After freezing, these levels were decreased to 60.5 and 72.8%, respectively. An
      insemination trial using frozen-thawed epididymal semen resulted in a lambing
      rate of 87.5%. Results show that this semen preservation method is robust and
      efficient and associated with high fertility. It may also be useful for other
      animal species.

PMID- 16905184
TI  - Fabrication of hydroxyapatite ultra-thin layer on gold surface and its
      application for quartz crystal microbalance technique.
AB  - We present a method for coating gold quartz crystal microbalance with dissipation
      (QCM-D) sensor with ultra-thin layer of hydroxyapatite nanocrystals evenly
      covering and tightly bound to the surface. The hydroxyapatite layer shows a plate
      like morphology and less than 20 nm in thickness. The hydroxyapatite sensor
      operated in liquid with high stability and sensitivity. The in-situ adsorption
      mechanism and conformational change of fibrinogen on gold, titanium and
      hydroxyapatite surfaces were investigated by QCM-D technique and Fourier
      transform infrared spectroscopy. The change of secondary structures of fibrinogen
      adsorbed on the surfaces depended on the adsorbed amounts of protein. The
      secondary structure of fibrinogen adsorbed on the surfaces changes with
      increasing coverage. This is explained by repulsion among fibrinogens, affecting
      water structure and thus the strength of fibrinogen interactions on the surface.
      The study indicates that the hydroxyapatite sensor is applicable for qualitative
      and conformational analysis of protein adsorption.

PMID- 16905185
TI  - Procoagulant activity of surface-immobilized Hageman factor.
AB  - Procoagulant activity of surface-immobilized coagulation factor XIIa (activated
      Hageman factor) is reported. Activity of FXIIa immobilized onto the surfaces of
      three silanized-glass procoagulants spanning a wide range of wettability was
      assayed in normal and FXII-deficient plasmas. Previously published mathematical
      models were used to characterize the procoagulant activity of protein-immobilized
      materials and soluble enzymes. Results show that FXIIa activity is unrelated to
      underlying procoagulant surface chemistry and is similar to soluble FXIIa
      activity. The uninfluential role of the surface on FXIIa suggests that the solid
      surface activates FXII in biomaterial-induced blood coagulation but is not
      otherwise involved in FXIIa activity as described by the classical mechanism.

PMID- 16905186
TI  - Combined topographical and chemical micropatterns for templating neuronal
      networks.
AB  - In vitro neuronal networks with geometrically defined features are desirable for
      studying long-term electrical activity within the neuron assembly and for
      interfacing with external microelectronic circuits. In standard cultures, the
      random spatial distribution and overlap of neurites makes this aim difficult;
      hence, many recent efforts have been made on creating patterned cellular
      circuits. Here, we present a novel method for creating a planar neural network
      that is compatible with optical devices. This method combines both topographical
      and chemical micropatterns onto which neurons can be cultured. Compared to other
      reported patterning techniques, our approach and choice of template appears to
      show both geometrical control over the formation of specific neurite connections
      at low plating density and compatibility with microelectronic circuits that
      stimulate and record neural activity.

PMID- 16905188
TI  - Signaling proteins in raft-like microdomains are essential for Ca2+ wave
      propagation in glial cells.
AB  - The hypothesis that calcium signaling proteins segregate into lipid raft-like
      microdomains was tested in isolated membranes of rat oligodendrocyte progenitor
      (OP) cells and astrocytes using Triton X-100 solubilization and density gradient
      centrifugation. Western blot analysis of gradient fractions showed co
      localization of caveolin-1 with proteins involved in the Ca2+ signaling cascade.
      These included agonist receptors, P2Y1, and M1, TRPC1, IP3R2, ryanodine receptor,
      as well as the G protein Galphaq and Homer. Membranes isolated from agonist
      stimulated astrocytes showed an enhanced recruitment of phospholipase C
      (PLCbeta1), IP3R2 and protein kinase C (PKC-alpha) into lipid raft fractions.
      IP3R2, TRPC1 and Homer co-immunoprecipitated, suggesting protein-protein
      interactions. Disruption of rafts by cholesterol depletion using methyl-beta
      cyclodextrin (beta-MCD) altered the distribution of caveolin-1 and GM1 to non
      raft fractions with higher densities. beta-MCD-induced disruption of rafts
      inhibited agonist-evoked Ca2+ wave propagation in astrocytes and attenuated wave
      speeds. These results indicate that in glial cells, Ca2+ signaling proteins might
      exist in organized membrane microdomains, and these complexes may include
      proteins from different cellular membrane systems. Such an organization is
      essential for Ca2+ wave propagation.

PMID- 16905187
TI  - Effect of low oxygen concentrations on trophoblast-like cell line invasion.
AB  - The applicability of trophoblast-like cell lines to the study of trophoblast
      function has been widely debated. The present study investigated the effect of
      oxygen on the invasiveness, apoptosis, proliferation and secreted proteases of
      four different trophoblast cell lines; HTR-8/SVneo, SGHPL-4, JEG3 and JAR. All
      experiments were performed at 20% and 3% oxygen for 24, 48 and 72h.
      Immunostaining for integrins alpha1, alpha6 and beta3, cytokeratin 7 and HLA-G
      was used to determine the phenotype of the different cell lines. Invasion was
      assessed using the Matrigel invasion assay. Immunostaining for M30 and Ki67
      determined levels of apoptosis and proliferation, respectively. Gelatin and
      casein/plasminogen zymography were performed on conditioned media to determine
      levels of secreted matrix metalloproteinase (MMP) 2 and MMP9 and urokinase
      plasminogen activator (uPA), respectively. None of the cell lines immunostained
      for all markers normally expressed by extravillous trophoblast cells.
      Invasiveness of HTR-8/SVneo and JEG3 cells cultured in 3% oxygen was increased
      after 24h but was inhibited by 72h in culture. Invasion of SGHPL-4 cells was
      inhibited after culture in 3% oxygen for 24h. Invasion by JAR cells was not
      affected by changes in oxygen concentration. The different cell lines also
      displayed different responses to culture period in 3% oxygen with respect to
      apoptosis, proliferation and secreted proteases. Care should be taken before
      results obtained using cell lines as a model for EVT are extrapolated to
      extravillous trophoblast cell behaviour in vivo.

PMID- 16905189
TI  - Levels of brominated flame retardants in blood in relation to levels in household
      air and dust.
AB  - Levels of tri- to decabrominated diphenyl ethers (BDEs), 1,2-bis(2,4,6
      tribromophenoxy)ethane (BTBPE) and 1,2-bis(pentabromophenyl)ethane (DeBDethane)
      were determined in air, sedimentary dust and human plasma from five households in
      Sweden. The levels of the individual BDEs in the plasma samples were in the same
      order of magnitude as in other studies of the general population in Scandinavia,
      and varied between non-detectable (<0.41 ng g(-1) l.w.) to 17 ng g(-1) (l.w.).
      BDE#28 and #47 were present in all air samples, with mean values of 0.015 and
      0.12 ng m(-3), respectively, except for one sample where the BDE#47 concentration
      was below the limit of detection (<0.17 ng m(-3)). BDE#209 was found in one of
      the five air samples at a concentration of 0.26 ng m(-3). DeBDethane was also
      detected in one sample, in which the BDE#209 level was below LOD (<0.021 ng m(
      3)), at a level of 0.023 ng m(-3). All the target compounds were found in the
      sedimentary dust samples at levels from 0.51 to 1600 ng g(-1), the highest
      concentration representing BDE#209. The most abundant components in plasma, air
      and dust were BDE#47, #99 and #209. In the plasma samples BDE#207 and #206 were
      also present at similar concentrations as BDE#47. In the sedimentary dust
      samples, DeBDethane was also among the most abundant BFRs. A positive
      relationship was found for the sumBDE concentrations in dust and plasma, although
      the relationship was strongly dependent on one of the five observations. BFR
      levels in dust and air were not dependent on the house characteristics such as
      living area, floor material or number of electronic devices.

PMID- 16905190
TI  - From comparative risk assessment to multi-criteria decision analysis and adaptive
      management: recent developments and applications.
AB  - Environmental risk assessment and decision-making strategies over the last
      several decades have become increasingly more sophisticated, information
      intensive, and complex, including such approaches as expert judgment, cost
      benefit analysis, and toxicological risk assessment. One tool that has been used
      to support environmental decision-making is comparative risk assessment (CRA),
      but CRA lacks a structured method for arriving at an optimal project alternative.
      Multi-criteria decision analysis (MCDA) provides better-supported techniques for
      the comparison of project alternatives based on decision matrices, and it also
      provides structured methods for the incorporation of project stakeholders'
      opinions in the ranking of alternatives. We argue that the inherent uncertainty
      in our ability to predict ecosystem evolution and response to different
      management policies requires shifting from optimization-based management to an
      adaptive management paradigm. This paper brings together a multidisciplinary
      review of existing decision-making approaches at regulatory agencies in the
      United States and Europe and synthesizes state-of-the-art research in CRA, MCDA,
      and adaptive management methods applicable to environmental remediation and
      restoration projects. We propose a basic decision analytic framework that couples
      MCDA with adaptive management and its public participation and stakeholder value
      elicitation methods, and we demonstrate application of the framework to a
      realistic case study based on contaminated sediment management issues in the New
      York/New Jersey Harbor.

PMID- 16905191
TI  - Kaposi's sarcoma-associated herpes virus complement control protein: KCP-
      complement inhibition and more.
AB  - The complement system is an important part of innate immunity providing immediate
      protection against pathogens without a need for previous exposure, as well as
      priming the adaptive immune response through opsonisation, leukocyte recruitment
      and enhancing humoral immune responses. Its importance is not only shown through
      recurring fulminant infections in individuals with complement component
      deficiencies, but also through the many complement evasion strategies discovered
      for a wide range of infectious microbes (including acquisition of endogenous host
      complement inhibitors and expression of own homologues). Knowledge of these
      mechanisms at a molecular level may aid development of vaccines and novel
      therapeutic strategies. Here, we review the structure-function studies of the
      membrane-bound complement inhibitor KCP that is expressed on the surface of
      Kaposi's sarcoma-associated herpesvirus (KSHV) virions and infected cells. KCP
      accelerates the decay of classical C3 convertase and induces the degradation of
      activated complement factors C4b and C3b by a serine proteinase, factor I.
      Molecular modeling and site-directed mutagenesis have identified sites on the
      surface of KCP required for complement inhibition and support the hypothesis that
      KCP has evolved to mimic the structure and function of endogenous human
      inhibitors. KCP additionally enhances virion binding to permissive cells through
      a heparin/heparan sulfate-binding site located at the N-terminus of the protein.

PMID- 16905192
TI  - The role of complement in biomaterial-induced inflammation.
AB  - Biomaterials are regularly used in various types of artificial tissues and
      organs, such as oxygenators, plasmapheresis equipment, hemodialysers, catheters,
      prostheses, stents, vascular grafts, miniature pumps, sensors and heart aids.
      Although progress has been made regarding bioincompatibility, many materials and
      procedures are associated with side effects, in particular bioincompatibility
      induced inflammation, infections and subsequent loss of function. After
      cardiopulmonary bypass, coagulopathies can occur and lead to cognitive
      disturbances, stroke and extended hospitalization. Hemodialysis is associated
      with anaphylatoid reactions that cause whole-body inflammation and may contribute
      to accelerated arteriosclerosis. Stents cause restenosis and, in severe cases,
      thrombotic reactions. This situation indicates that there is still a need to try
      to understand the mechanisms involved in these incompatibility reactions in order
      to be able to improve the biomaterials and to develop treatments that attenuate
      the reactions and thereby reduce patients' discomfort, treatment time and cost.
      This overview deals with the role of complement in the incompatibility reactions
      that occur when biomaterials come in contact with blood and other body fluids.

PMID- 16905194
TI  - Interferon-gamma release assays in children--no better than tuberculin skin
      testing?

PMID- 16905193
TI  - Transplantation of autologous serum-derived cultivated corneal epithelial
      equivalents for the treatment of severe ocular surface disease.
AB  - PURPOSE: To evaluate the use of autologous serum (AS)-derived cultivated corneal
      epithelial transplantation for the treatment of severe ocular surface disease.
      DESIGN: Retrospective noncomparative case series. PARTICIPANTS: Nine eyes from 9
      patients with total limbal stem cell deficiency were studied. These consisted of
      2 eyes with Stevens-Johnson syndrome, 1 with chemical injury, 1 with ocular
      cicatricial pemphigoid, 1 with Salzmann corneal dystrophy, 1 with aniridia, 1
      with graft-versus-host disease, and 2 with idiopathic ocular surface disease.
      METHODS: Autologous serum obtained from patients was used for cultivating corneal
      epithelial cells on an amniotic membrane substrate. These AS-derived corneal
      epithelial equivalents were compared with those derived from fetal bovine serum
      (FBS)-supplemented medium. At the time of surgery, complete removal of the
      corneal pannus and conjunctiva up to 3 mm from the limbus was performed.
      Allogeneic (7 cases) and autologous (2 cases) AS-derived cultivated corneal
      epithelial equivalents were transplanted onto the ocular surface. Postoperative
      follow-up included serial slit-lamp examinations with fluorescein staining, as
      well as photographic documentation. MAIN OUTCOME MEASURES: Ocular surface
      reconstruction with corneal epithelialization, graft integrity, visual acuity,
      and postoperative complications. RESULTS: The corneal epithelial sheets
      cultivated in AS- and FBS-supplemented media were morphologically similar, and
      demonstrated the normal expression of tissue-specific keratins and junctional
      specialization assembly proteins. After transplantation, complete corneal
      epithelialization was achieved within 2 to 5 days. All eyes demonstrated an
      improvement in visual acuity by > or =2 lines. During the follow-up period of
      14.6+/-4.36 months, the corneal surface of all patients remained stable and
      transparent, without significant complications. CONCLUSIONS: Transplantation of
      AS-derived cultivated corneal epithelial equivalents was shown to be a feasible
      method of treating patients with severe ocular surface disease. The use of AS is
      of clinical importance in the development of autologous xenobiotic-free
      bioengineered ocular surface equivalents for clinical transplantation.

PMID- 16905195
TI  - The structural evolution of dopamine D3 receptor ligands: structure-activity
      relationships and selected neuropharmacological aspects.
AB  - "Evolution consists largely of molecular tinkering."-Following the famous concept
      of the molecular geneticist and medicine Nobel laureate Francois Jacob, in this
      review we describe the structural evolution of dopamine D3 receptor ligands from
      the natural agonist dopamine (DA) to highly potent and subtype selective new
      agents by bioisosteric tinkering with well-established and privileged or novel
      and fancy chemical functionalities and scaffolds. Some of the more than 200
      ligands presented herein have already achieved therapeutic or scientific value up
      to now, some will most likely achieve it in the future. Hence, great importance
      is not only attached to the relationship between structure and activity of the
      ligands, but also to their utility as pharmacological tools in animal models or
      as therapeutics in patients with neurological diseases or other disorders.

PMID- 16905196
TI  - Interplay between computational models and cognitive electrophysiology in visual
      word recognition.
AB  - In this article, we discuss the relevance of electrophysiological data to the
      enterprise of analyzing and understanding the reading process. Specifically, we
      detail how the event-related brain potential (ERP) technique (and its magnetic
      counterpart) can aid in development of models of visual word recognition. Any
      viable and accurate account of reading must take into account the temporal and
      anatomical constraints imposed by the fact that reading is a human brain
      function. We believe that neurophysiological (especially, although not limited to
      electrophysiological) data can serve an essential reference in the development of
      biologically realistic models of reading. We assess just how well extant
      electrophysiological data comport with specific predictions of existing
      computational models and offer some suggestions for the kinds of research that
      can address some of the remaining open questions.

PMID- 16905197
TI  - Contingency management: schedule effects.
AB  - Contingency management interventions provide reinforcement for abstaining from
      drugs and withhold reinforcement when drug use is detected. Previous work
      demonstrates that the reinforcement schedule with which reinforcement is
      delivered modulates the efficacy of the intervention. This pilot study explores
      the effects of reinforcement in methamphetamine-dependent individuals. Results
      suggest that schedules incorporating an increasing magnitude of reinforcement for
      consecutive abstinences with a reset in reinforcer magnitude for a positive drug
      test produce superior results.

PMID- 16905199
TI  - Complement activation in autoimmune demyelination: dual role in neuroinflammation
      and neuroprotection.
AB  - Multiple sclerosis and its animal model experimental allergic encephalomyelitis
      are inflammatory demyelinating diseases of the central nervous system mediated by
      activated lymphocytes, macrophages/microglia and the complement system.
      Complement activation and the C5b-9 terminal complex contribute to the
      pathogenesis of these diseases through its role to promote demyelination. C5b-9
      was also shown to protect oligodendrocytes from apoptosis both in vitro and in
      vivo. Our findings indicate that activation of complement and C5b-9 assembly
      plays a pro-inflammatory role in the acute phase, but may also be
      neuroprotective.

PMID- 16905200
TI  - Medical and surgical management of subperiosteal orbital abscess secondary to
      acute sinusitis in children.
AB  - OBJECTIVE: To evaluate the presentations and outcomes of pediatric subperiosteal
      orbital abscesses (SPOA) secondary to acute sinusitis. STUDY DESIGN: Case series
      SETTING: Tertiary children's hospital. PATIENTS: Forty-three admissions diagnosed
      with SPOA by clinical presentation and contrast enhanced computed tomography
      (CECT) were retrospectively reviewed. MAIN OUTCOME MEASURES: Clinical
      presentations, CECT dimensions, treatment, outcomes, and microbiology. RESULTS:
      Eighteen/43 (42%) patients resolved their infection with medical management only,
      including five children older than nine. Twenty-five/43 (58%) children underwent
      surgical drainage. Purulence was identified in 22 of 25 surgical patients, and
      the most common organism was Streptococcus milleri (7 patients). Compared to 22
      patients with drained purulence, the 18 patients with abscesses managed medically
      had significant differences for: chemosis in 2/18 (11.1%) versus 14/22 (63.6%,
      p=0.001), proptosis in 10/18 (55.6%) versus 20/22 (90.9%, p=0.025), elevated
      intraocular pressure (IOP) in 0/18 (0%) versus 11/22 (50%, p<0.001), severe
      restriction of extraocular movements in 1/18 (5.6%) versus 12/22 (54.5%,
      p=0.002), and length of stay (4.3 versus 5.8 days, p=0.038). The dimensions of
      medial SPOA managed medically were significantly smaller on CECT compared to
      surgically drained purulent SPOA: width (0.25 versus 1.46cm, p<0.001), height
      (0.73 versus 1.35cm, p=0.002), and length (1.1 versus 1.86cm, p=0.004).
      Persistent morbidities occurred in no patients managed medically and in 2/25 (8%)
      managed surgically. CONCLUSIONS: Children with small medial SPOA without
      significant ocular signs may be managed medically with favorable outcomes.
      Proposed criteria for medical management of medial SPOA include: (1) normal
      vision, pupil, and retina; (2) no ophthalmoplegia; (3) IOP<20mmHg; (4) proptosis
      of 5mm or less; and (5) abscess width of 4mm or less. In contrast to prior
      series, older children with SPOA were managed successfully with medical therapy.

PMID- 16905201
TI  - Interplay between PI3K/Akt and MAPK signaling pathways in DNA-damaging drug
      induced apoptosis.
AB  - In order to elucidate the role of the mitogen-activated protein kinases,
      including JNK, p38 MAPK and ERK, as well as the survival-associated PI3K/Akt
      signaling pathway, in the response to chemotherapy, we have conducted a
      comparative study regarding the effects of doxorubicin on these pathways.
      Doxorubicin was determined to elicit the apoptosis of NIH3T3 cells in a dose
      dependent manner. Prior to cell death, both Akt and p38 MAPK were transiently
      activated, and subsequently inactivated almost wholly, whereas ERK and JNK
      evidenced sustained activations in response to the drug treatment. The inhibition
      of PI3K/Akt and p38 MAPK both accelerated and enhanced doxorubicin-induced
      apoptosis and ERK inhibition apparently exerted negative effect on apoptosis. The
      modulation of PI3K/Akt activation by treatment of LY294002 or expression of Akt
      mutants such as Akt-DN or Myr-Akt exerted a significant effect on the activation
      of ERK1/2. We also observed that PI3K/Akt and sustained ERK activation were
      associated intimately with the etoposide-induced apoptosis. Taken together, our
      results clearly suggest that the differential regulation of the PI3K/Akt, ERK1/2,
      and p38 MAPK signaling pathways are crucial in the context of DNA-damaging drug
      induced apoptosis, and this has compelled us to propose that the sustained
      activation of ERK1/2 pathway may be generally involved in the apoptosis induced
      by anticancer DNA-damaging drugs, including doxorubicin and etoposide.

PMID- 16905202
TI  - Longevity index (LI%) and centenarity index (CI%): new indicators to evaluate the
      characteristics of aging process in the Italian population.
AB  - Centenarians represent a group of population displaying the most rapid expansion.
      This progressive increase of the presence of centenarians is a multi-factorial
      phenomenon, which is due to the improvements of the environmental conditions and
      the life style and also to the progress of the medical science. In order to
      obtain a more reliable estimate of the longevity per gender and territorial
      entities, we propose two new indicators. (i) The ratio between the
      ultranonagenarians and the total population above 65 years old (called longevity
      index: LI%); (ii) the ratio between the centenarians and the total population
      above 90 years old (called centenarity index: CI%). An analysis of the data of
      the Italian National Office of Statistics (ISTAT, ) using these two indicators
      demonstrates that the subjects above the age of 90 are more frequent in the
      regions of Central and Northern Italy, which are more developed regarding the
      economic conditions and technological progress. Nevertheless, the Southern and
      Insular regions of Italy have a higher occurrence of centenarians among the
      ultranonagenarian population, and also a higher prevalence of male centenarians,
      as compared to the northern regions. This demonstrates that achievement of the
      threshold of 100 years old does not require only particular socio-economic
      conditions, but also an adequate climate and environment, as well as a favorable
      genetic composition.

PMID- 16905203
TI  - Pneumopericardium masquerading as an acute myocardial infarction.

PMID- 16905204
TI  - An effective vascular-healing agent after coronary stent implantation: estrogen.

PMID- 16905205
TI  - The economic consequences of health shocks: evidence from Vietnam.
AB  - This paper finds that the incomes of urban households are more vulnerable to
      health shocks than rural households, that health shocks may precipitate increases
      in unearned income that partially offset reductions in earned income and large
      increases in medical spending even among insured households. It also finds that
      households spend less on food following a health shock, but more on budget items
      such as housing and electricity. Measures of household health shocks used include
      a recent death of a working-age household member, a long inpatient spell, and a
      recent sizeable drop in the body mass index of the household head.

PMID- 16905206
TI  - Effect of selective growth media on the differentiation of Salmonella enterica
      serovars by Fourier-Transform Mid-Infrared Spectroscopy.
AB  - Salmonella enterica serovars are prevalent foodborne pathogens responsible for
      high numbers of salmonellosis each year. Complex Fourier-transform infrared
      (FTIR) spectra offer unique biochemical fingerprints of bacteria with bands due
      to major cellular components. Growth media effects on discrimination of
      Salmonella serovars by FTIR spectroscopy were investigated and a novel sample
      preparation technique was developed. S. enterica strains from six serovars were
      grown on xylose lysine desoxycholate (XLD), Miller-Mallinson (MM), and plate
      count (PCA) agar as a control (37 degrees C, 24 h). Isolated colonies were
      suspended in 50% acetonitrile and centrifuged; the remaining pellet was placed on
      an AMTIR (attenuated total reflectance) crystal and dried under vacuum.
      Classification models (Soft Independent Modeling of Class Analogy, SIMCA),
      generated from derivatized infrared spectra (1300-900 cm-1 or 1200-900 cm-1),
      successfully discriminated among Salmonella strains with major discrimination
      from 1000-970 cm-1 associated to stretching modes of O-specific polysaccharide
      chains of lipopolysaccharides. Sample treatment with acetonitrile enhanced safe
      handling of the bacteria, removed interfering signals and improved the
      discriminating ability of SIMCA. All media were able to discriminate the S.
      enterica strains studied, varying in discriminating peaks and class distances in
      SIMCA classification. This methodology, with the production of large libraries of
      pathogenic bacteria, could be applied for the rapid monitoring of bacterial
      contamination in food with minimal sample manipulation.

PMID- 16905207
TI  - Phosphorylated histone H2AX in relation to cell survival in tumor cells and
      xenografts exposed to single and fractionated doses of X-rays.
AB  - BACKGROUND AND PURPOSE: Human tumor cell lines grown as monolayers or xenograft
      tumors were exposed to single or multiple fractions of X-rays and the ability to
      use residual gammaH2AX to identify radiosensitive cells was assessed. MATERIALS
      AND METHODS: Twenty-four hour after exposure to single or daily fractions of X
      rays, human tumor cells from monolayers or xenografts were analyzed for
      clonogenic surviving fraction. Cells were also fixed and labeled with anti
      gammaH2AX antibodies for analysis by flow and image cytometry. The relative
      amount of residual gammaH2AX and the percentage of cells with <3 foci were
      compared with the clonogenic surviving fraction measured for the same population.
      RESULTS: The fraction of gammaH2AX remaining 24h after X-irradiation relative to
      peak levels 1h after exposure was correlated with radiosensitivity (SF2) for 18
      human tumor cell lines. The fraction of SiHa, C33A and WiDr cells with <3
      gammaH2AX foci was predictive of clonogenic surviving fraction for both monolayer
      cells exposed to either single doses or up to 5 fractions. Similar results were
      obtained using cells from xenograft tumors of irradiated mice. CONCLUSION: The
      percentage of tumor cells that retain gammaH2AX foci 24h after single or
      fractionated doses appears to be a useful measure of cellular radiosensitivity
      that is potentially applicable in the clinic.

PMID- 16905208
TI  - Molecular responses of rectal cancer to preoperative chemoradiation.
AB  - BACKGROUND AND PURPOSE: Some rectal cancers respond well to preoperative
      neoadjuvant therapy while others are inherently resistant or develop resistance
      during the treatment. To understand the mechanism underlying these differences,
      several markers that might be prognostic or predictive of downstaging in response
      to chemoradiotherapy in patients with rectal cancer were evaluated. MATERIAL AND
      METHODS: Thirty patients were enrolled in this study. All were treated with
      preoperative chemoradiation (45Gy in 25 fractions+5-FU). Paraffin-embedded
      sections obtained before and after therapy were stained by H&E, for COX-2, and
      Ki67. In addition, osteopontin and IL-6 concentrations were determined in blood
      samples obtained before, during, and after therapy. RESULTS: COX-2 expression
      increased in 67% (n=8/12) of the patients from a median of 0% before to 74% after
      therapy (p=0.009). Ki67 median positivity diminished from 90% to 45% in 83%
      (n=10/12) of cases (p=0.007). Osteopontin expression showed no significant
      changes during therapy, whereas IL-6 expression levels increased in 70% (n=19/27)
      of all patients (p<0.001). For osteopontin and IL-6, patients with a complete
      response tended to have lower pre-therapy levels. Moreover, osteopontin was much
      higher before (p=0.02) and after therapy (p=0.01) in patients who later developed
      metastases. CONCLUSIONS: Chemoradiotherapy seems to affect expression of COX-2
      and Ki67 which indicates that these proteins might be of importance in predicting
      long-term outcome. Moreover, osteopontin might be a marker of metastases.

PMID- 16905209
TI  - Feasibility study of using MOSFET detectors for in vivo dosimetry during
      permanent low-dose-rate prostate implants.
AB  - PURPOSE: To investigate the feasibility of using new micro-MOSFET detectors for
      QA and in vivo dosimetry of the urethra during transperineal interstitial
      permanent prostate implants (TIPPB). METHODS AND MATERIALS: This study involves
      measurements for several patients who have undergone the implant procedure with
      iodine-125 seeds. A new micro-MOSFET detector is used as a tool for in vivo
      measurement of the initial dose rate within the urethra. MOSFETs are calibrated
      using a single special order calibration seed. The angular response is
      investigated in a 100 kVp X-ray beam. RESULTS: micro-MOSFETs are found to have a
      calibration factor of 0.03 cGy/mV for low energy X-rays and a high isotropic
      response (within 2.5%). Prostate volume and shape changes during TIPPB due to
      edema caused by the trauma of needle insertion, making it difficult to achieve
      the planned implant geometry and hence the desired dose distribution. MOSFET
      measurements help us to evaluate the overall quality of the implant, by analyzing
      the maximum dose received by urethra, the prostate base coverage, the length of
      the prostatic urethra that is irradiated, and the apex coverage. CONCLUSIONS: We
      demonstrate that ease of use, quick calibration and the instantaneous reading of
      accumulated dose make micro-MOSFETs feasible for in vivo dosimetry during TIPPB.

PMID- 16905210
TI  - Cardiac and pulmonary complication probabilities for breast cancer patients after
      routine end-inspiration gated radiotherapy.
AB  - PURPOSE: Substantial reductions of radiation doses to heart and lung can be
      achieved using breathing adaptation of adjuvant radiotherapy following
      conservative surgery for breast cancer. The purpose of this study was to estimate
      the radiobiological implications after routine use of an end-inspiration gated
      treatment, and to compare the results with predictions based on pre-clinical CT
      studies. PATIENTS AND METHODS: Nineteen consecutive patients with axillary lymph
      node-positive left-sided breast cancer were referred for adjuvant radiotherapy
      after breast conserving surgery. Treatment was performed with gating in the end
      inspiration phase of audio-coached enhanced free breathing. The target intended
      to encompass the remaining breast, ipsilateral internal mammary and
      periclavicular nodes, and the prescription dose was 48Gy in 24 fractions. A three
      field mono-isocentric conformal technique using deep tangentials and a
      supraclavicular field was employed. NTCPs were calculated using the relative
      seriality model for the heart, and the model proposed by Burman et al. for the
      lung. The observed values were compared to those predicted from two previous CT
      studies for a deep inspiration breath-hold technique and an uncoached end
      inspiration gating technique. RESULTS: The ipsilateral lung V(50) (relative
      volume receiving more than 50% of the prescription dose) had a median value of
      23.7% (range 10.8-35.1%) over the patient population. The corresponding median
      lung pneumonitis probability was 1.1% (range 0-14%). The median heart V(50) was
      0.8% (range 0-19.1%) with a corresponding median cardiac mortality NTCP of 0.1%
      (range 0-5.7%). These results compare well with the predictions of our previous
      CT-studies. There is a significant reduction in dose to the left anterior
      descending coronary artery for the enhanced end-inspiration gating technique
      compared to the uncoached end-inspiration technique employed in the CT-studies.
      CONCLUSIONS: In a routine clinical practice involving adjuvant breast
      radiotherapy gated in an enhanced end-inspiration phase, remarkably low doses to
      organs at risk are observed. The corresponding cardiac and pulmonary complication
      risks are of the order of 1% and smaller.

PMID- 16905211
TI  - Improvement of esophageal adenocarcinoma cell and xenograft responses to
      radiation by targeting cyclin-dependent kinases.
AB  - BACKGROUND AND PURPOSE: Concurrent chemo-radiotherapy before surgery is standard
      treatment protocol for esophageal cancer with a less than 30% complete response
      due to resistance to therapy. The aim of this study was to determine whether
      molecular targeting approach using an inhibitor of cyclin-dependent kinases,
      flavopiridol, can help overcome the resistance to radiotherapy. MATERIALS AND
      METHODS: SEG-1 cells (human esophageal adenocarcinoma) were exposed to gamma-rays
      with and without flavopiridol treatment and assayed for clonogenic survival,
      apoptosis, cell cycle distribution, and Western blot analysis. Efficacy of
      flavopiridol in enhancing tumor response to radiation was determined by tumor
      growth delay assay using SEG-1 tumor xenografts generated in nude mice. RESULTS:
      The clonogenic cell survival assay data showed that flavopiridol (300 nM, 24h),
      when given either before or after radiation, significantly enhanced the
      radiosensitivity of SEG-1 cells. The cells were accumulated at G1 phase of the
      cell cycle by flavopiridol that was associated with downregulation of p-cdk-1, p
      cdk-2, cyclin D1 and p-Rb expression. Flavopiridol by itself induced apoptosis in
      SEG-1 cells and also enhanced the radiation-induced apoptosis, associated with an
      increase in cleaved poly ADP-ribose polymerase. Reduction in phosphorylation of
      RNA polymerase II by flavopiridol suggested that flavopiridol inhibited the
      transcriptional activity. In vivo studies with SEG-1 tumor xenografts showed that
      flavopiridol, either given before or after radiation, greatly enhanced the effect
      of tumor irradiation. CONCLUSIONS: Flavopiridol treatment significantly enhanced
      SEG-1 cell radiosensitivity as well as the radioresponse of SEG-1 tumor
      xenografts. The underlying mechanisms are multiple, including cell cycle
      redistribution, apoptosis, and transcriptional inhibition. These preclinical data
      suggest that flavopiridol has the potential to increase the radioresponse of
      esophageal adenocarcinomas.

PMID- 16905213
TI  - Imaging hypoxia after oxygenation-modification: comparing [18F]FMISO
      autoradiography with pimonidazole immunohistochemistry in human xenograft tumors.
AB  - PURPOSE: Hypoxia is one of the reasons for radiation therapy resistance. Positron
      emission tomography using (18)F-labeled misonidazole ([(18)F]FMISO) is a non
      invasive method of imaging tumor hypoxia. Aim of this study was to validate
      [(18)F]FMISO against the clinically most widely used hypoxic cell marker
      pimonidazole under different oxygenation conditions. MATERIALS AND METHODS: One
      human head and neck squamous cell carcinoma (SCCNij3) and two human glioblastoma
      (E102 and E106) xenograft tumor lines were studied after injection of
      [(18)F]FMISO and pimonidazole. Control mice were compared with a second group
      breathing carbogen to reduce tumor hypoxia and with a third group with clamped
      tumors to increase hypoxia. Tumor sections were analyzed on a phosphor imaging
      system and consecutively stained immunohistochemically (IHC) for visualization of
      pimonidazole. Pixel-by-pixel analysis was performed and the hypoxic fraction,
      obtained after segmentation of the pimonidazole signal, was related to the mean
      optical density of [(18)F]FMISO and pimonidazole. RESULTS: A moderate pixel-by
      pixel correlation between [(18)F]FMISO autoradiography and pimonidazole IHC was
      found for the control tumors, after carbogen breathing and after clamping for
      SCCNij3. For E102 and E106, mean signal intensities for pimonidazole
      significantly decreased after carbogen breathing and increased after clamping,
      mean [(18)F]FMISO signal intensities increased significantly after clamping and a
      significant correlation between the hypoxic fractions and the mean [(18)F]FMISO
      signal intensities was found. CONCLUSIONS: [(18)F]FMISO autoradiography and
      pimonidazole immunohistochemistry can both be used to visualize treatment induced
      changes in tumor hypoxia. However, the response to these modifications differs
      widely between xenograft tumor lines.

PMID- 16905212
TI  - CpG oligodeoxynucleotides are potent enhancers of radio- and chemoresponses of
      murine tumors.
AB  - BACKGROUND AND PURPOSE: Synthetic oligodeoxynucleotides (ODNs) containing
      unmethylated cytosine-guanine (CpG) motifs bind to Toll-like receptor 9 (TLR9)
      and stimulate both innate and adaptive immune reactions and possess anti-tumor
      activity. We recently reported that CpG ODN 1826 strongly enhances radioresponse
      of both immunogenic [Milas L, Mason K, Ariga H, et al. CpG oligodeoxynucleotide
      enhances tumor response to radiation. Cancer Res 2004;64:5074-7] and non
      immunogenic [Mason KA, Ariga H, Neal R, et al. Targeting toll-like receptor-9
      with CpG oligodeoxynucleotides enhances tumor response to fractionated
      radiotherapy. Clin Cancer Res 2005;11:361-9] murine tumors. Using two immunogenic
      murine tumors, a fibrosarcoma (FSa) and a mammary carcinoma (MCa-K), the present
      study explored whether CpG ODN 1826 also improves the response of murine tumors
      to the chemotherapeutic agent docetaxel (DOC). MATERIALS AND METHODS: CpG ODN
      1826 (100 microg) was given sc three times: when leg tumors were 6mm, when they
      grew to 8mm and again 1 week later. DOC (33 mg/kg iv) and local tumor radiation
      (10Gy) were given when tumors were 8mm. Effects of the treatments were assayed by
      tumor growth delay, defined as days for tumors to grow from 8 to 12 mm in
      diameter. RESULTS: Treatment with CpG ODN 1826 resulted in strongly enhanced
      response of FSa tumors to radiation and MCa-K tumors to the chemotherapeutic
      agent DOC. Enhancement of tumor treatment response was demonstrated by a strong
      prolongation in the primary tumor treatment endpoint, tumor growth delay.
      Coincidentally, this treatment also resulted in a higher rate of tumor cure than
      that observed after tumor radiotherapy or chemotherapy alone. When all three
      agents were combined the effect was comparable to that of the combination of CpG
      ODN 1826 with radiation in the case of FSa or of the combination of CpG ODN 1826
      with DOC in the case of MCa-K. CONCLUSION: Overall results show that CpG ODN 1826
      can markedly improve tumor response to radiation and chemotherapy (DOC),
      suggesting that CpG ODNs have potential to be beneficial when used singly or in
      combination with other standard treatment modalities such as taxane chemotherapy,
      radiotherapy or both.

PMID- 16905214
TI  - Lymphoblastoid cell lines differing in p53 status show clear differences in basal
      gene expression with minor changes after irradiation.
AB  - BACKGROUND AND PURPOSE: The genetic profile as determined by microarray is
      considered to be an ideal marker of the individual radiosensitivity. However, it
      is still an open question, whether this profile has to be determined prior to or
      only after irradiation, since the expression of some genes is affected by
      irradiation. These changes are induced mainly due to a p53-dependent
      transactivation. MATERIALS AND METHODS: In this study gene expression profiles
      were measured for 3 lymphoblastoid cell lines differing in p53 status (p53 wt:
      TK6; p53null: TK6E6, p53mut: WTK1) measured either prior to or 3h after exposure
      to 2Gy. The gene expression profile was determined using the Affymetrix Human HG
      U133A GeneChip and for selective genes, variation in gene expression was
      validated by qRT-PCR. In addition, different assays were used to characterize the
      radioresponse of these three strains. RESULTS: The three strains were found to be
      different in all aspects of radiosensitivity studied. Cells with p53wt showed
      more apoptosis, slightly stronger arrest in G1, but less lethal aberrations and a
      lower viability when compared to cells with mutated p53, whereas cells absent in
      p53 are characterized by an intermediate response. The gene expression profile
      measured prior to irradiation already revealed huge differences. Significance
      analysis of microarrays (SAM) identified 141 genes that changed expression
      twofold or more with a false discovery rate (FDR) of 5.4%. When compared to
      p53null cell line with p53wt showed a twofold difference in up- or down
      regulation in 28 genes. A much higher variation was even found when p53mut cells
      were compared with p53null cells with a twofold difference in even 123 genes. The
      respective genes were found to be involved mainly in apoptosis, cell cycle
      regulation, metabolisms and signalling but with only one gene relevant for DNA
      repair. Radiation was found to affect this profile solely for cells with p53wt
      with a twofold significant up-regulation in only five genes. For selective genes
      (BCL2, CASP1, CCND2, DDB2, XPC, RAD51C, SESN1, FUCA1, CDKN1A, MDM2, XPC) array
      data were confirmed by qRT-PCR. CONCLUSION: The result, that the gene expression
      profile of lymphoblastoid cells differing in p53 status already displayed clear
      differences when measured prior to irradiation with only few changes after
      irradiation, which are solely seen for p53wt cells, suggests, that the
      differences in radiosensitivity observed for these cells are primarily determined
      by the variation in expression profile present already prior to irradiation.

PMID- 16905215
TI  - Social support and ambulatory blood pressure: an examination of both receiving
      and giving.
AB  - The relationship between the social network and physical health has been studied
      extensively and it has consistently been shown that individuals live longer, have
      fewer physical symptoms of illness, and have lower blood pressure when they are a
      member of a social network than when they are isolated. Much of the research has
      focused on the benefits of receiving social support from the network and the
      effects of giving to others within the network have been neglected. The goal of
      the present research was to systematically investigate the relationship between
      giving and ambulatory blood pressure. Systolic blood pressure, diastolic blood
      pressure, mean arterial pressure, and heart rate were recorded every 30 min
      during the day and every 60 min at night during a 24-h period. Linear mixed
      models analyses revealed that lower systolic and diastolic blood pressure and
      mean arterial pressure were related to giving social support. Furthermore,
      correlational analyses revealed that participants with a higher tendency to give
      social support reported greater received social support, greater self-efficacy,
      greater self-esteem, less depression, and less stress than participants with a
      lower tendency to give social support to others. Structural equation modeling was
      also used to test a proposed model that giving and receiving social support
      represent separate pathways predicting blood pressure and health. From this
      study, it appears that giving social support may represent a unique construct
      from receiving social support and may exert a unique effect on health.

PMID- 16905217
TI  - Biodesulfurization of DBT in tetradecane and crude oil by a facultative
      thermophilic bacterium Mycobacterium goodii X7B.
AB  - Mycobacterium goodii X7B, a facultative thermophilic bacterium, cleaving the C-S
      bond of dibenzothiophene via a sulfur-specific pathway, was investigated for DBT
      in tetradecane and crude oil desulfurization. The extent of growth was improved
      by fed-batch culture controlled at a constant pH. The total sulfur level of
      dibenzothiophene in tetradecane, was reduced by 99%, from 200 to 2 ppm within 24h
      at 40 degrees C. After 72 h treatment, 59% of the total sulfur content in
      Liaoning crude oil was removed, from 3600 to 1478 ppm.

PMID- 16905216
TI  - Dietary supplementation of arachidonic and docosahexaenoic acids improves
      cognitive dysfunction.
AB  - Age-dependent increase of peroxidation of membrane fatty acids such as
      arachidonic acid (ARA) and docosahexaenoic acid (DHA) in neurons was reported to
      cause a decline of the hippocampal long-term potentiation (LTP) and cognitive
      dysfunction in rodents. Although supplementation of ARA and DHA can improve LTP
      and cognitive function in rodents, their effects in humans are unknown. The
      present work was undertaken to study whether ARA and DHA have beneficial effects
      in human amnesic patients. The subjects were 21 mild cognitive dysfunction (12
      MCI-A with supplementation and 9 MIC-P with placebo), 10 organic brain lesions
      (organic), and 8 Alzheimer's disease (AD). The cognitive functions were evaluated
      using Japanese version of repeatable battery for assessment of neuropsychological
      status (RBANS) at two time points: before and 90 days after the supplementation
      of 240 mg/day ARA and DHA, or 240 mg/day of olive oil, respectively. MCI-A group
      showed a significant improvement of the immediate memory and attention score. In
      addition, organic group showed a significant improvement of immediate and delayed
      memories. However, there were no significant improvements of each score in AD and
      MCI-P groups. It is suggested from these data that ARA and DHA supplementation
      can improve the cognitive dysfunction due to organic brain damages or aging.

PMID- 16905218
TI  - Systematic lactose-functionalization of amphiphilic octaamine macrocycle as a
      gene carrier. Optimization of the charge, size, toxicity, and receptor factors
      for hepatocyte targeting.
AB  - We investigated the transfection properties of singly and triply lactose
      functionalized derivatives, Lac(1) and Lac(3), and non-glycosylated one, Lac(0),
      of calix[4]resorcarene-based amphiphilic octaamine 1 in light of those previously
      reported for more extensively glycosylated compounds Lac(5) and Lac(8). They all
      strongly bind to the luciferase-encoding plasmid DNA pCMVluc (7040 base-pairs)
      with a saturation stoichiometry of Lac(n)/P approximately =0.5 (n=0, 1, or 3) or
      0.7 (n=5 or 8), where P stands for a phosphate moiety of the plasmid DNA. The
      resulting carrier-DNA conjugates are positively charged and monomeric
      (monomolecular with respect to DNA) as such when n=0 or 1, neutral and monomeric
      when n=3, or neutral and aggregated when n=5 or 8. Transfection of HeLa (uterine)
      and HepG2 (hepatic) cell lines shows a general trend of decreasing luciferase
      expression efficiencies (E) in lively cells as well as cytotoxicities with
      increasing n's. The cell selectivities for HepG2 over HeLa sharply increase with
      increasing n's; E(HepG2)/E(HeLa)=0.3, 0.6, 7, 14, and 120 for Lac(0), Lac(1),
      Lac(3), Lac(5), and Lac(8), respectively, as a result of specific receptor
      pathway involving the asialoglycoprotein receptors on the hepatic (HepG2) cell
      surfaces and clustering lactose moieties of the carrier-DNA conjugates. The
      toxicity-corrected, overall efficiency of gene delivery to hepatocytes is
      optimized at Lac(3), which forms compactly packed (approximately 40 nm), charge
      masked (xi approximately = 0 mV), and less toxic virus-like particles capable of
      receptor-mediated hepatocyte targeting.

PMID- 16905219
TI  - Uptake studies in rat Peyer's patches, cytotoxicity and release studies of
      alginate coated chitosan nanoparticles for mucosal vaccination.
AB  - The design of particulate vaccine delivery systems, particularly for mucosal
      surfaces, has been a focus of interest in recent years. In this context, we have
      previously described the development and the characterization of a new nanosized
      delivery system, consisting of a model antigen adsorbed to chitosan particles and
      coated with sodium alginate. In the present work the ovalbumin release profiles
      from these coated nanoparticles in different pH buffers were investigated and
      compared to those of the uncoated particles. Cytotoxicity of the polymers and
      nanoparticles was assessed using the MTT assay. Finally, particle uptake studies
      in rat Peyer's patches were performed. It was demonstrated that the coating of
      the nanoparticles with sodium alginate not only avoided a burst release observed
      with uncoated particles but also increased the stability of the particles at pH
      6.8 and 7.4 at 37 degrees C. At neutral pH, the release was lower than 5% after
      3.5 h incubation in a low ionic strength buffer. For both, chitosan and alginate
      polymers, and for the nanoparticles, comparable cell viability data close to
      100%, were obtained. Additionally, based on confocal laser scanning microscopy
      observations, it was shown that alginate coated nanoparticles were able to be
      taken up by rat Peyer's patches, rendering them suitable carriers for intestinal
      mucosal vaccination.

PMID- 16905220
TI  - Biochemical and histological effects of 26 weeks of glycyrrhizin treatment in
      chronic hepatitis C: a randomized phase II trial.
AB  - BACKGROUND/AIMS: Phase I/II studies of 4 weeks duration have confirmed the ALT
      lowering effect of glycyrrhizin in Western chronic hepatitis C patients. Our aim
      was to determine the dose frequency of glycyrrhizin required to maintain the ALT
      response beyond 4 weeks and evaluate its effect on liver histology and quality of
      life. METHODS: HCV-RNA-positive patients with elevated ALT and marked fibrosis or
      necro-inflammation who were not eligible for interferon therapy were treated for
      4 weeks with six infusions weekly of glycyrrhizin. Patients with an ALT response
      at week 4 were randomized to continue treatment for 22 weeks in three dose
      frequency groups: 6x, 3x or once weekly. RESULTS: 72/121 (60%) patients were
      randomized. At the end of treatment the ALT response was maintained in 60%, 24%
      and 9% of patients in the 6x, 3x, and once weekly groups, respectively (p<0.001).
      In ALT responders the necro-inflammation score improved non-significantly
      compared to ALT non-responders. Quality of life assessed by SF-36 increased in
      patients treated with the study drug, albeit unrelated to the occurrence of ALT
      response. CONCLUSIONS: ALT responses induced by 4 weeks glycyrrhizin therapy can
      be maintained in a subset of chronic hepatitis C patients receiving at least
      three injections weekly. The observed ALT response did not translate in a
      significant histological improvement after 6 months treatment.

PMID- 16905221
TI  - How can we define expanded criteria for liver donors?

PMID- 16905222
TI  - Spatial and temporal variability of water repellency in a sandy soil contaminated
      with tar oil and heavy metals.
AB  - Water repellency can induce preferential flow and thus affect water flow and
      contaminant transport at hazardous waste sites. Since the spatial patterns of
      water repellency are mostly unknown, it is problematic to use numerical transport
      models to predict leachate composition. In this study, the spatial variability of
      soil water repellency was studied at an industrial site contaminated with tar
      oil, chromium, copper and arsenic. The persistence of water repellency was
      assessed by the water drop penetration time (WDPT), and the degree of water
      repellency was quantified by the ethanol percentage (EP) test. Measurements were
      made at the soil surface along 3.5-12.1 m long transects at different times
      between March and October 2002. The spatial variability of WDPT, EP, water
      content, and organic matter content was quantified by variogram analyses. Both
      the persistence and the degree of water repellency varied seasonally, with the
      highest water repellency during the summer months. The correlation lengths of
      WDPT values ranged between 16 and 406 cm, whereas EP values showed no spatial
      correlation. For field-moist samples, a critical soil water threshold, below
      which water repellency prevails, was estimated to be 2.5-4%. For oven dry
      samples, the WDPT values were dependent on the water content prior to drying. The
      wide range of correlation lengths and the temporal dynamics of spatial repellency
      patterns suggest that simulations of solute leaching must consider the spatial
      and temporal variability of soil hydrophobic properties.

PMID- 16905223
TI  - VIP provides cellular protection through a specific splice variant of the PACAP
      receptor: a new neuroprotection target.
AB  - Vasoactive intestinal peptide (VIP) was known to provide neuroprotection. Three
      VIP receptors have been cloned: VPAC1, VPAC2 and PAC1. A specific splice variant
      of PAC1 in the third cytoplasmatic loop, hop2, was implicated in VIP-related
      neuroprotection. We aimed to clone the hop2 splice variant, examine its affinity
      to VIP and investigate whether it mediates the VIP-related neuroprotective
      activity. The PAC1 cDNA was cloned from rat cerebral astrocytes. Using genetic
      manipulation the hop2 splice variant was obtained, then inserted into an
      expression vector and transfected into COS-7 cells that were used for binding
      assays. Results showed that VIP bound the cloned hop2 splice variant. Stearyl
      neurotensin(6-11) VIP(7-28) (SNH), an antagonist for VIP, was also found to bind
      hop2. In addition, VIP protected COS-7 cells expressing hop2 from oxidative
      stress. Parallel assays demonstrated that VIP increased cAMP accumulation in COS
      7 cells expressing hop2. These results support the hypothesis that hop2 mediates
      the cytoprotective effects attributed to VIP.

PMID- 16905224
TI  - Novel methods of quantitative real-time PCR data analysis in a murine
      Helicobacter pylori vaccine model.
AB  - Monitoring of Helicobacter pylori in the stomach is important to assess the
      efficacy of new vaccines against the pathogen. To realise the full potential of
      quantitative real-time PCR (q-PCR), this technology has to offer accurate and
      easy models of post-PCR data analysis. In this work, we used a variety of
      absolute and relative approaches of q-PCR data analysis to monitor the H. pylori
      infection in the stomach of immunized mice. Relative quantification was performed
      with Ct-based methods, with the DART program, and with two methods based on the
      mathematical analysis of raw fluorescence kinetics, the LinReg program and the
      Sigmoidal Curve Fitting Method. The different calculation methods were validated
      in mice immunized with cell lysates of Lactococcus lactis expressing the H.
      pylori urease subunit B in combination with cholera toxin. The H. pylori load was
      found to be reduced in immunized mice by a factor of 50-144, depending on the
      calculation method employed. We found that relative quantification using DART,
      LinReg and Sigmoidal Curve Fitting methods generated similar results (infection
      ratios of 54-58) with absolute quantification results (54-65). Results were very
      different to those using relative quantification Ct-based methods without a
      correction for PCR efficiency (ratio of 92-144) and with results based on
      conventional culture method (ratio of 34). Overall, this study demonstrates that
      q-PCR associated with a relative quantification analysis is a powerful tool for
      the monitoring of microorganisms in tissue. It could be used as an alternative to
      standard curve approach especially for the investigation of microbial load in
      vaccine models.

PMID- 16905225
TI  - A practical demonstration in modelling diclofenac and propranolol river water
      concentrations using a GIS hydrology model in a rural UK catchment.
AB  - An existing GIS hydrology water quality model, LF2000-WQX, was applied to predict
      the concentrations of the pharmaceuticals diclofenac and propranalol in
      catchments. As a practical exercise the predominantly rural Tamar (UK) catchment
      was chosen. Consumption, excretion, and fate data were used to estimate the
      pharmaceutical input load for the model. The predicted concentrations throughout
      most of the catchment were 1 ng/L or less under low flow (90th percentile)
      conditions. However, at a few locations, downstream of small sewage treatment
      plants, concentrations above 25 ng/L were predicted. This exercise shows that it
      is relatively straightforward to predict the concentrations of new and emerging
      organic microcontaminants in real catchments using existing GIS hydrology water
      quality models. Further testing will be required to establish their accuracy.

PMID- 16905226
TI  - Plant senescence: a mechanism for nutrient release in temperate agricultural
      wetlands.
AB  - The beneficial uptake of nutrients by wetland plants is countered to some extent
      by nutrient release back into the aquatic environment due to vegetative die-back.
      This current study examined whether Leersia oryzoides, a common wetland plant,
      exhibits luxury uptake of nutrients from simulated farm runoff. The study also
      tested whether with subsequent decomposition, these nutrients are released back
      into the water column. When exposed to elevated (>2mg/L N and P) runoff, L.
      oryzoides assimilated significantly higher concentrations of nitrogen (p<0.001)
      and phosphorus (p<0.001) in above-ground biomass as compared to non-enriched
      treatments (<0.05 mg/L N and P). Subsequently, senescence of enriched above
      ground biomass yielded significantly higher concentrations of phosphorus (2.19+/
      0.84 mg P/L). Using L. oryzoides as our model, this study demonstrates nitrogen
      and phosphorus sequestration during the growing season and release of phosphorus
      in the winter.

PMID- 16905227
TI  - Nematode communities in contaminated river sediments.
AB  - Nematode communities of eight sites from three river catchments were investigated
      in terms of the genera composition, feeding types, and life-history strategists.
      The sampling sites showed a gradient of anthropogenic contamination with heavy
      metals and organic pollutants being important factors in differentiating the
      sites. Nematode community structure was related to sediment pollution and the
      hydro-morphological structure of the sampling sites. Heavily contaminated sites
      were characterized by communities with high relative abundances of omnivorous and
      predacious nematodes (Tobrilus, c-p 3; Mononchus, c-p 4), while sites with low to
      medium contamination were dominated by bacterivorous nematodes (Monhystera,
      Daptonema; c-p 2) or suction feeders (Dorylaimus, c-p 4). The relatively high
      Maturity Index values in the heavily polluted sites were surprising. Nematodes
      turned out to be a suitable organism group for monitoring sediment quality, with
      generic composition being the most accurate indicator for assessing differences
      in nematode community structure.

PMID- 16905228
TI  - The Pb pollution fingerprint at Lochnagar: the historical record and current
      status of Pb isotopes.
AB  - Ratios of 206Pb/207Pb in a Lochnagar sediment core slowly decline from c. 1.32 at
      140 cm to c. 1.23 at 9 cm, and then rapidly decline to c. 1.15 at the surface.
      Ninety percent of the Pb in the surface sediments can be attributed to
      anthropogenic sources. The 206Pb/207Pb ratio data imply that catchment peat
      surface contains a higher fraction of anthropogenic Pb than the sediment surface.
      The 206Pb/207Pb ratios in the surface of the sediment core are consistent with
      ratios in trapped sediments collected annually between 1998 and 2003. However,
      there is no significant decline in these recent samples suggesting that the
      reduction in atmospheric Pb emissions has not yet been recorded by the sediments
      due to Pb inputs from the catchment. As catchment peats store about 840 kg
      previously deposited anthropogenic Pb since 1860, it is likely that catchment
      inputs will continue to affect future 206Pb/207Pb ratios.

PMID- 16905229
TI  - Solanum nigrum grown in contaminated soil: effect of arbuscular mycorrhizal fungi
      on zinc accumulation and histolocalisation.
AB  - Zn tissue accumulation in Solanum nigrum grown in a non-contaminated and a
      naturally contaminated Zn matrix and the effect of inoculation with different
      arbuscular mycorrhizal fungi (AMF) on metal uptake were assessed. S. nigrum grown
      in the contaminated soil always presented higher Zn accumulation in the tissues,
      accumulating up to 1622 mg Zn kg(-1). The presence of both Glomus claroideum and
      Glomus intraradices enhanced the uptake and accumulation of Zn by S. nigrum (up
      to 83 and 49% higher Zn accumulation, respectively). The main deposits of the
      metal were found in the intercellular spaces and in the cell walls of the root
      tissues, as revealed by autometallography, with the inoculation with different
      AMF species causing no differences in the location of Zn accumulation. These
      findings indicate that S. nigrum inoculated with selected heavy metal tolerant
      AMF presents extracting and accumulating capacities, constituting a potentially
      suitable remediation method for Zn polluted soils.

PMID- 16905230
TI  - Objective and perceived neighborhood environment, individual SES and psychosocial
      factors, and self-rated health: an analysis of older adults in Cook County,
      Illinois.
AB  - This article investigates the relationship among objectively assessed
      neighborhood socio-economic status (SES), subjective perceptions of neighborhood
      environment, individual SES and psychosocial factors, and self-rated health among
      middle-aged and older adults. Analysis of data from a representative sample of
      adults, aged 50-67 years in Cook County, Illinois, shows a significant
      association between objective neighborhood SES and self-rated health after
      controlling for age, gender, and race/ethnicity, but the effect is substantially
      explained by individual SES and neighborhood perceptions. By contrast, perceived
      neighborhood quality (i.e., subjective ratings of neighborhood physical, social,
      and service environments) exhibits a significant effect after controlling for
      individual socio-demographic factors as well as neighborhood SES. In turn, the
      effects of perceived neighborhood environment on health are partially explained
      by the psychosocial factors of loneliness, depression, hostility, and stress, but
      not by perceived social support or social networks. In sum, the research supports
      a model in which the effects of neighborhood SES on self-rated health act through
      sequential pathways of individual SES, perceptions of neighborhood quality, and
      psychosocial status.

PMID- 16905231
TI  - Purity and the dangers of regenerative medicine: regulatory innovation of human
      tissue-engineered technology.
AB  - This paper examines the development of innovation in human tissue technologies as
      a form of regenerative medicine, firstly by applying 'pollution ideas' to
      contemporary trends in its risk regulation and to the processes of regulatory
      policy formation, and secondly by analysing the classificatory processes deployed
      in regulatory policy. The analysis draws upon data from fieldwork and documentary
      materials with a focus on the UK and EU (2002-05) and explores four arenas:
      governance and regulatory policy; commercialisation and the market;
      'evidentiality' manifest in evidence-based policy; and publics' and technology
      users' values and ethics. The analysis suggests that there is a trend toward
      'purification' across these arenas, both material and socio-political. A common
      process of partitioning is found in stakeholders' attempts to define a clear
      terrain, which the field of tissue-engineered technology might occupy. We
      conclude that pollution ideas and partitioning processes are useful in
      understanding regulatory ordering and innovation in the emerging technological
      zone of human tissue engineering.

PMID- 16905233
TI  - An evaluation of the maximized survey-derived daily intake (MSDI) as a practical
      method to estimate intake of flavouring substances.
AB  - Realistic estimates of intake are essential for risk assessments of flavouring
      agents, since substantial over or underestimations introduce inaccuracies into
      such evaluations. The objectives of this study were to examine the relationship
      between intakes estimated using methods based on the reported volume of
      production [e.g., maximized survey-derived daily intake (MSDI)] versus use-level
      data [e.g., possible average daily intake (PADI) and modified theoretical added
      maximum daily intake (mTAMDI)]. The impact of volatility, self-limiting
      organoleptic properties and whether 10% of the population are eaters, an
      assumption in the MSDI calculation, on intake estimates were investigated.
      Analyses on 221 flavouring substances showed that intake estimates derived from
      MSDI correlated with values determined from detailed 14-day menu-census data,
      PADI, and mTAMDI. Comparisons of menu-census intake data adjusted to account for
      factors such as volatile losses showed that MSDI estimates are realistic and
      sufficiently conservative, whereas mTAMDI results in substantial overestimates of
      intake. Very few flavours have less than 10% eaters, and in the worst case, this
      assumption underestimates percent eaters by a factor of about 4. This
      investigation supports the use of MSDI as a conservative yet practical method to
      estimate intake of flavouring substances.

PMID- 16905234
TI  - Evaluation of the reproductive toxicity of patulin in growing male rats.
AB  - Patulin is a mycotoxin produced by several Penicillium, Aspergillus and
      Byssachlamys species. Patulin can be produced on different food products
      including fruits, grains, cheese, cured meats, but in natural situations patulin
      is exclusively found in apple and apple products. Patulin, at dose of 0.1mg/kg
      bw/day, was administered by gavage to the growing male rats aged 5-6 week for 60
      or 90 days. At the end of the experiment, sperm counts and morphology were
      investigated. Also, effects of patulin on the epididymis, seminal vesicle and
      prostate tissues were examined histopathologically and morphologically. While
      sperm counts increased in patulin-treated rats for 60 days, sperm counts in
      patulin-treated rats for 90 days decreased compared to the corresponding control
      group. Patulin affected sperm morphology of growing male rats. Tail abnormalities
      like bent and/or coiled tails, and sticking of sperm tails were observed. A
      significant change was not determined in absolute and relative weights of the
      seminal vesicle and prostate of patulin-treated rats. While absolute cauda
      epididymal weights increased in rats treated with patulin for 60 days, absolute
      and relative cauda epididymal weights reduced in rats treated with patulin for 90
      days. In histologic examination, some histopathological changes were observed in
      the epididymis and prostate tissues of rats in patulin treatment groups.

PMID- 16905232
TI  - Ganoderma tsugae in vivo modulates Th1/Th2 and macrophage responses in an
      allergic murine model.
AB  - We have reported that Ganoderma tsugae supplementation alleviates bronchoalveolar
      inflammation in an airway sensitization and challenge model with female BALB/c
      mice. However, the effects of G. tsugae supplementation in vivo on serum antibody
      levels, splenocyte and peritoneal microphage immune responses have not yet been
      determined. In this study, serum antibody levels, cytokines and splenocyte
      chemical mediators and peritoneal macrophage cultures from ovalbumin (OVA)
      sensitized and -challenged mice were examined after continuously consuming G.
      tsugae supplementation diets for 5 weeks. The results showed that OVA
      sensitization and challenge significantly (P<0.05) decreased the spontaneous
      production of IL-2 (Th1) cytokine, but significantly (P<0.05) increased
      spontaneous and OVA-stimulated IL-4 (Th2) production in splenocyte cultures from
      experimental mice. OVA administration significantly decreased both spontaneous
      and LPS/IFN-gamma-stimulated IL-1beta and IL-6 levels in peritoneal macrophage
      cultures from experimental mice. However, dietary supplementation with G. tsugae
      significantly increased spontaneous IL-2 level, but slightly decreased
      spontaneous IL-4 level in cultured splenocyte supernatants in the experimental
      groups. G. tsugae supplementation enhanced pro-inflammatory cytokines IL-1beta
      and IL-6 production in cultured peritoneal macrophages. However, the nitric oxide
      level from cultured peritoneal macrophages and serum OVA-specific IgE and IgG(2a)
      antibody levels was not significantly affected. These results suggest that OVA
      sensitization and challenge induced a Th2-skewed splenocyte response and
      decreased peritoneal macrophage cytokine secretion. G. tsugae supplementation in
      vivo modulated the Th1/Th2 balance and enhanced macrophage immune responses.
      However, the supplementation diet could not fully reverse the Th2-skewed
      responses to level of Th1-skewed responses.

PMID- 16905235
TI  - The effects of repeated exposure to sub-toxic doses of plecomacrolide antibiotics
      on the endocrine pancreas.
AB  - The plecomacrolide vacuolar ATPase inhibitors bafilomycin and concanamycin
      contaminate tuberous vegetables and damage pancreatic islets in mice. The
      consequences of repeated exposure of adult mice to sub-toxic doses of bafilomycin
      A1 or concanamycin A was examined by injection of the plecomacrolides on each of
      five consecutive days. There was a significant reduction in islet size in female
      C57BL/6j mice (p<0.004 and p<0.0001 respectively). There were no significant
      differences in fasted insulin levels and beta cell mass between treated and
      control groups but oral glucose tolerance worsened with increasing age in BALB/c
      female mice injected with concanamycin A. Streptozotocin reduced glucose
      tolerance and islet number but not islet size in all strains and sexes. Chronic
      exposure of C57BL/6j mice to concanamycin A for 16 weeks caused a significant
      reduction in islet size in both sexes and a significant increase in the spleen
      weight of female mice (p<0.001). We conclude that repeated exposure to small
      quantities of vacuolar proton-translocating ATPase inhibitory plecomacrolides
      reduces islet size and can lead to glucose intolerance, possibly due to impaired
      maintenance of pancreatic islets. This may lead to earlier progression to beta
      cell failure and insulin deficiency in those at risk of diabetes.

PMID- 16905236
TI  - Phthalate exposure and male infertility.
AB  - Phthalates have been used as additives in industrial products since the 1930s,
      and are universally considered to be ubiquitous environmental contaminants. The
      general population is exposed to phthalates through consumer products, as well as
      diet and medical treatments. Animal studies showing the existence of an
      association between some phthalates and testicular toxicity have generated public
      and scientific concern about the potential adverse effects of environmental
      changes on male reproductive health. In particular, prenatal exposure to
      phthalates seems to play a relevant role in determining these adverse effects
      given that human exposure has been demonstrated to begin during the intrauterine
      life. Unprecedented declines in fertility rates and semen quality of antenatal
      origin have been reported during the last half of the 20th century in developed
      countries and increasing interest exists on the potential relationship between
      exposure to environmental contaminants, including phthalates, and human male
      reproductive health. Here we review the data that support or discounts the
      evidence existing to date linking phthalate exposure and the decline of human
      male fertility, especially in developed countries.

PMID- 16905237
TI  - Energy landscape of the ribosomal decoding center.
AB  - The ribosome decodes the genetic information that resides in nucleic acids. A key
      component of the decoding mechanism is a conformational switch in the decoding
      center of the small ribosomal subunit discovered in high-resolution X-ray
      crystallography studies. It is known that small subunit nucleotides A1492 and
      A1493 flip out of helix 44 upon transfer RNA (tRNA) binding; however, the
      operation principles of this switch remain unknown. Replica molecular dynamics
      simulations reveal a low free energy barrier between flipped-out and flipped-in
      states, consistent with a switch that can be controlled by shifting the
      equilibrium between states. The barrier determined by the simulations is
      sufficiently small for the binding of ligands, such as tRNAs or aminoglycoside
      antibiotics, to shift the equilibrium.

PMID- 16905238
TI  - From the molecular characterization of iodide transporters to the prevention of
      radioactive iodide exposure.
AB  - In the event of a nuclear reactor accident, the major public health risk will
      likely result from the release and dispersion of volatile radio-iodines. Upon
      body exposure and food ingestion, these radio-iodines are concentrated in the
      thyroid, resulting in substantial thyroidal irradiation and accordingly causing
      thyroid cancers. Stable potassium iodide (KI) effectively blocks thyroid iodine
      uptake and is thus used in iodide prophylaxis for reactor accidents. The
      efficiency of KI is directly related to the physiological inhibition of the
      thyroid function in the presence of high plasma iodide concentrations. This
      regulation is called the Wolff-Chaikoff effect. However, to be fully effective,
      KI should be administered shortly before or immediately after radioiodine
      exposure. If KI is provided only several hours after exposure, it will elicit the
      opposite effect e.g. lead to an increase in the thyroid irradiation dose. To
      date, clear evaluation of the benefit and the potential toxicity of KI
      administration remain difficult, and additional data are needed. We outline in
      this review the molecular characterization of KI-induced regulation of the
      thyroid function. Significant advances in the knowledge of the iodide transport
      mechanisms and thyroid physiology have been made. Recently developed molecular
      tools should help clarify iodide metabolism and the Wolff-Chaikoff effect. The
      major goals are clarifying the factors which increase thyroid cancer risk after a
      reactor accident and improving the KI administration protocol. These will
      ultimately lead to the development of novel strategies to decrease thyroid
      irradiation after radio-iodine exposure.

PMID- 16905239
TI  - Degradation of procyanidins by Aspergillus fumigatus: identification of a novel
      aromatic ring cleavage product.
AB  - Aspergillus fumigatus was able to grow on apple-purified procyanidins (PCs). PCs
      concentration decreased 30% over the first 60 h of liquid fermentation. The mean
      degree of polymerization (DPn) of apple-purified PCs increased from 8 to 15
      during the fermentation. A fungal enzyme extract from the liquid fermentation was
      used to study procyanidin B2 [(-)-epicatechin-(4beta-8)-(-)-epicatechin]
      degradation. The major degradation product (PB2-X) had a retention time of 10.5
      min and a molecular mass at m/z 609. High-performance liquid
      chromatography/multiple fragment mass spectrometry (HPLC/MS(n)) was used for the
      structural characterization of PB2-X as well as that of thiolysis-treated PB2-X.
      Twelve fragment ions at m/z 565, 547, 457, 439 (two fragment ions), 421, 413,
      377, 395, 351, 287 and 277 were completely identified. It was therefore deduced
      that the terminal unit of procyanidin B2 dimer was modified by an oxygenase from
      A. fumigatus leaving the extension unit intact. In addition, FT-IR analysis
      confirmed a lactone formation in (-)-epicatechin moiety involved in oxidative
      degradation. Two reaction schemes were postulated for the interpretation of the
      results.

PMID- 16905240
TI  - Health and environmental assessment of mercury exposure in a gold mining
      community in Western Mindanao, Philippines.
AB  - The small-scale gold mining activities using mercury began in the late 1980s in
      Sibutad, Western Mindanao. It is located very near the Murcielagos Bay with
      tailing ponds directly discharging into bodies of water. This cross-sectional
      study aimed to determine the health and environmental effects of gold mining
      activities on the community. Residents were randomly selected and classified into
      two groups, namely, the directly exposed and indirectly exposed populations using
      a set inclusion criteria. Complete medical and laboratory examinations were
      performed. Environmental and biologic samples were collected for total mercury
      and methylmercury determinations. The results showed that the directly exposed
      group had significantly higher mean blood total mercury and methylmercury levels
      in comparison with the indirectly exposed population. Although there were no
      significant differences between hair total mercury and methylmercury levels,
      there was a trend for higher levels of these biomarkers among the directly
      exposed residents as compared with the unexposed group. The absence of
      statistically significant differences may be attributable to the small sample
      size. Ambient air quality monitoring for mercury exceeded the allowable levels.
      However, levels of mercury in drinking water and sediments were within allowable
      limits. Frequency of gastrointestinal complaints was significantly associated
      with elevated hair methylmercury levels (p=0.02). Also, there appears to be a
      trend towards higher blood total mercury levels and frequency of gastrointestinal
      complaints (p=0.09). An interesting finding in this study was the increasing
      incidence of elevated diastolic blood pressure with elevated hair total mercury
      levels (p=0.07). Mercury storage at home is a risk factor.

PMID- 16905241
TI  - Seminal plasma cytokines and chemokines in prostate inflammation: interleukin 8
      as a predictive biomarker in chronic prostatitis/chronic pelvic pain syndrome and
      benign prostatic hyperplasia.
AB  - OBJECTIVE: This prospective study quantified cytokine and chemokine levels in
      seminal plasma of patients with chronic prostatitis/chronic pelvic pain syndrome
      (CP/CPPS) and benign prostatic hyperplasia (BPH), to evaluate inflammatory
      mediators as possible surrogate markers for diagnosis and treatment efficacy.
      METHODS: Seminal plasma levels of eight cytokines and nine chemokines were
      evaluated by multiplex arrays in 83 men: 20 healthy controls and 9 men with
      CP/CPPS IIIA, 31 with CP/CPPS IIIB, and 23 with BPH. Prostate samples obtained by
      transurethral resection of the prostate from 13 patients with BPH were analysed
      by immunohistochemistry to detect interleukin 8 (IL-8)-producing cells and
      characterise inflammatory infiltrates. RESULTS: Significantly increased levels of
      cytokines (IL-1alpha, IL-1beta, IL-6, IL-10, IL12p70) and chemokines (CCL1, CCL3,
      CCL4, CCL17, CCL22, CXCL8/IL-8) were observed in seminal plasmas from patients
      with CP/CPPS or BPH. However, only IL-8 was significantly elevated compared to
      controls (median [quartiles] 1984 [1164-2444] pg/ml), in patients with CP/CPPS
      IIIA (15,240 [10,630-19,501] pg/ml; p<0.0001), CP/CPPS IIIB (2983 [2033-5287]
      pg/ml; p=0.008), and BPH (5044 [3063-11,795] pg/ml, p<0.0001), discriminating
      CP/CPPS IIIA versus IIIB (accuracy=0.882+/-0.078; p=0.001). Inflammatory
      infiltrates were detected in prostate samples from 13 of 13 BPH patients, and IL
      8-producing prostate cells in 11 of 13 samples. IL-8 concentration in seminal
      plasma was positively correlated with symptom score and prostate-specific antigen
      levels both in CP/CPPS and BPH patients. CONCLUSIONS: IL-8 is expressed in situ
      by epithelial and stromal prostate cells and is functional, as shown by
      recruitment of cells expressing cognate receptors in BPH prostate tissue,
      indicating its involvement in disease pathogenesis. Among all the cytokines and
      chemokines analysed, IL-8 appears to be the most reliable and predictive
      surrogate marker to diagnose prostate inflammatory conditions, such as CP/CPPS
      and BPH.

PMID- 16905242
TI  - Perioperative complications of radical cystectomy in a contemporary series.
AB  - OBJECTIVES: Radical cystectomy is the preferred standard treatment for patients
      with muscle-invasive bladder cancer. With improvements in intra- and
      perioperative care lower complication rates have been reported. We
      retrospectively evaluated our series of patients who underwent radical cystectomy
      for advanced bladder cancer for perioperative complications as well as operative
      time, postoperative hospital stay and transfusion rates. PATIENTS AND METHODS:
      Between April 1993 and August 2005, 516 radical cystectomies were performed for
      muscle infiltrating transitional cell carcinoma and other types of neoplastic
      diseases of the bladder at our institution. The average age was 66.3 yr (31-89).
      RESULTS: The perioperative mortality rate was 0.8%. A total of 141 patients
      (27.3%) developed at least one perioperative complication. The most frequent
      medical complications were subileus in 20 (3.9%) patients, deep venous thrombosis
      in 24 (4.7%), and enterocolitis in 10 (1.9%). Surgical complications included
      pelvic lymphoceles in 42 (8.1%) patients, wound dehiscence in 46 (8.9%), pelvic
      hematoma in 4 (0.8%), peritonitis in 4 (0.8%) and small bowel obstruction in 4
      (0.8%). The total early reoperation rate was 6.2%. Operative time, postoperative
      hospital stay and average number of blood units transfused decreased over the
      period 1993-2005. CONCLUSIONS: Radical cystectomy today is a procedure with an
      acceptable rate of perioperative morbidity and mortality. Improvements in
      surgical technique and anaesthesia as well as increased quality of perioperative
      care in recent years have resulted in reduced morbidity and shorter hospital
      stay.

PMID- 16905243
TI  - The effect of a catecholate chelator as a redox agent in Fenton-based reactions
      on degradation of lignin-model substrates and on COD removal from effluent of an
      ECF kraft pulp mill.
AB  - We evaluated the effect of a catecholate chelator as a redox agent in Fenton
      based reactions (known as chelator-mediated Fenton reaction-CMFR), in the
      presence of three different transition metals ions (Fe(2+), Fe(3+) and Cu(2+)) by
      determining the oxidative capability of CMFR towards lignin-model substrates. The
      potential application of mediated Fenton-based reactions as a novel process to
      treat pulp mill effluent was evaluated and monitored by chemical oxygen demand
      (COD) and total phenol removals from a combination of the effluents generated
      during an ECF bleaching stage. The catecholate chelator 3,4-dihydroxiphenilacetic
      acid (DOPAC) reduced both Fe(3+) and Cu(2+), in addition, the maximum Cu(2+)
      reduction activity was reached in a shorter time than for Fe(3+) reduction,
      however, the highest metal reduction activity was observed with Fe(3+). When
      DOPAC was added to Fenton-based reactions (Fe(3+)/H(2)O(2), Fe(2+)/H(2)O(2),
      Cu(2+)/H(2)O(2)) an increase in oxidative activities of these reactions were
      found as they resulted in great degradation improvement of the lignin-model
      substrates azure B, phenol red and syringaldazine. The same increase in oxidative
      capability of Fenton-based reactions in the presence of DOPAC was observed after
      effluent treatment, expressed by the increase in COD removal, namely, an increase
      in the range of about 70% in COD removal when Fe(2+) or Fe(3+) was the catalytic
      metal and about 25% for Cu(2+). However CMFR lead to an increase in total phenol
      content. As COD removal by CMFR system using Fe(3+) and Fe(2+) was not
      significantly different and that Fe(3+) ions promoted lesser increase in total
      phenol content, Fe(3+) was chosen for experimental optimization. At optimum
      conditions, 75% of COD and 30% of total phenol removal were achieved.

PMID- 16905244
TI  - Disinfection by-product precursors reduction by various coagulation techniques in
      Istanbul water supplies.
AB  - Coagulation process can be used to control natural organic matter (NOM) during
      drinking water production. The effectiveness of the coagulation process appeared
      to depend on the pH of coagulation rather than coagulant dosages. Jar tests
      conducted with depressed pH levels at different coagulation conditions removed
      more dissolved organic carbon (DOC) than those at moderate pH levels. For low DOC
      waters, like Omerli Lake Water (OLW), additional treatment would be necessary to
      achieve enhanced removal of NOM. In this study, three different coagulation
      techniques were used to remove disinfection by-products (DBP) precursors from
      three Istanbul surface water supplies. Jar test results indicate that optimize
      coagulation (OC) can enhance the removal of DBP precursors, and the removal of
      DOC could be improved from the current average of 15% to an average of 56% at the
      three sites tested. At lower pH, ferric coagulants generally performed better for
      removal of DBP precursors than did alum.

PMID- 16905245
TI  - Adsorption of heavy metal ions from aqueous solution by crosslinked carboxymethyl
      konjac glucomannan.
AB  - Crosslinked carboxymethyl konjac glucomannan (CMKGM) with degrees of substitution
      (DS) 0.265 and 0.550 were prepared through reaction of monochloroacetic acid
      (MCA), konjac glucomannan (KGM) and epichlorohydrin and used to adsorb Cu(2+),
      Pb(2+) and Cd(2+) ions from the aqueous solutions. Regardless of the metal ion
      species, the adsorption capacity rapidly reached equilibrium within 20min and
      adsorption followed second-order kinetic equation. The effect of pH on adsorption
      was apparent, the appropriate range was 5-6. The adsorptions of three metal ions
      are well followed as the Langmuir adsorption isotherm. The maximum adsorption
      capacity (Q(m)) and Langmuir constant (b) of CMKGM (DS=0.550) for Pb(2+) were
      41.7mg/g and 0.305mg/L. These values were higher than those for Cu(2+) and
      Cd(2+). Among the tested ions, the order of adsorption capacity was
      Pb(2+)>Cu(2+)>Cd(2+) in mass basis. The regeneration study indicates that CMKGM
      could be used repeatedly without significantly changing their adsorption
      capacities and desorption percentage.

PMID- 16905246
TI  - Comment on "Factors influencing the removal of fluoride from aqueous solution by
      calcined Mg-Al-CO3 layered double hydroxides".
AB  - Lv et al. [L. Lv, J. He, M. Wei, D.G. Evans, X. Duan, Factors influencing the
      removal of fluoride from aqueous solution by calcined Mg-Al-CO3 layered double
      hydroxides, J. Hazard. Mater. B 133 (2006) 119-128] previously investigated the
      fluoride removal using calcined Mg-Al-CO3 layered double hydroxides (CLDH) as the
      sorbents. The present comment further discusses the mechanism of fluoride
      adsorption onto CLDH.

PMID- 16905247
TI  - Study of thermal decomposition of methyl ethyl ketone peroxide using DSC and
      simulation.
AB  - Methyl ethyl ketone peroxide (MEKPO) is a typical organic peroxide with thermally
      unstable nature that has been broadly employed in the manufacturing process of
      acrylic resins, as a hardening agent for fiberglass-reinforced plastics, and as a
      curing agent for unsaturated polyester resins. The aim of this study was to
      identify the characteristics of MEKPO 31 wt.% while mixing with contaminants,
      such as H(2)SO(4), HCl, and NaCl under runaway conditions. To acquire the thermal
      runaway data, DSC and a simulation were used for thermal analysis. The results
      showed that the thermal decomposition of MEKPO and MEKPO+H(2)SO(4) follows two
      stages. The first one can be modeled by using an empirical nth order rate
      equation. The second stage can be modeled as autocatalytic. MEKPO+HCl and
      MEKPO+NaCl included two independent autocatalytic reactions. The decomposition of
      MEKPO in the presence of Cl- ions (added in MEKPO either in the form of HCl or
      NaCl) follows a significantly different path, an earlier decomposition "onset"
      temperature, higher amount of generated thermal power and smaller temperature of
      no return (T(NR)) and time to maximum rate (TMR) values. Simulations based on
      experimental data indicated that the effect of H(2)SO(4) was the most dangerous
      contaminant on MEKPO 31 wt.%. However, the impact of Cl ions was also important.
      It is therefore recommended that the means of fire fighting employed for this
      substance to be free of Cl-.

PMID- 16905248
TI  - Synthesis and photocatalytic property of SnO2/TiO2 nanotubes composites.
AB  - SnO2/TiO2 nanotubes composite photocatalysts with different SnO2 contents were
      successfully synthesized by means of a simple solvothermal process. The
      synthesized products were characterized physically by X-ray diffraction (XRD) and
      high-resolution transmission electron microscope (HRTEM). The composite
      photocatalysts can not only make the target pollutant, methylene blue (MB),
      adsorbed at a high concentration level around the surface of the composites but
      also decrease the recombination rate of electron-hole pairs so as to achieve good
      photocatalytic performance. The effect of SnO2 contents on the photocatalytic
      activities of the composites was also investigated. The results showed that the
      SnO2/TiO2 nanotubes composite photocatalyst with 5 wt.% SnO2 loading had the
      highest photocatalytic efficiency.

PMID- 16905249
TI  - Ozonation of acid yellow 17 dye in a semi-batch bubble column.
AB  - A semi-batch bubble column was used to evaluate the effect of ozonation on the
      removal of acid yellow 17 dye from water. Results indicate that ozonation is very
      effective at removing acid yellow 17 dye from synthetic textile wastewater. The
      ozone consumed to apparent dye removal ratio ranged from 2 to 15,000 mg ozone per
      mg of dye decolorized and was dependent on both ozonation time and apparent dye
      concentration. The biodegradability of the dye wastewater was evaluated by
      monitoring changes in 5-day biochemical oxygen demand (BOD5) with respect to
      chemical oxygen demand (COD). Results indicate that the wastewater
      biodegradability increased with an increase in ozonation time. Film theory was
      used to kinetically model the gas-liquid reactions occurring in the reactor.
      Modeling results indicated that during the first 10-15 min of ozonation, the
      system could be characterized by a fast, pseudo-first-order regime. With
      continued ozonation, system kinetics transitioned through a moderate then to a
      slow regime. Successful modeling of this period required use of a kinetic
      equation corresponding to a more inclusive condition. Model results are
      presented.

PMID- 16905250
TI  - Chloride homeostasis differentially affects GABA(A) receptor- and glycine
      receptor-mediated effects on spontaneous circuit activity in hippocampal cell
      culture.
AB  - The potassium-chloride cotransporter 2 (KCC2)-dependent intracellular chloride
      level determines whether neurons respond to GABA and/or glycine by depolarization
      or hyperpolarization. However, still unknown is the role of KCC2-dependent
      chloride homeostasis in regulating the spontaneous activity of neuronal circuits
      via GABA(A) receptor (GABA(A)R) and the glycine receptor (GlyR). In this study,
      patch-clamp recordings were performed to measure the change of spontaneous
      neuronal activity in cultured hippocampal neurons. Our results showed that
      inhibition of KCC2 with furosemide, as well as blockade of GABA(A)R with
      bicuculline, significantly enhanced circuit activity. Perfusion with bicuculline
      further enhanced the effects of furosemide on spontaneous circuit activity, while
      furosemide did not alter the effects of bicuculline. Surprisingly, blockade of
      GlyR not only induced obvious tonic currents, but also significantly decreased
      spontaneous synaptic activity. Moreover, inhibition of KCC2 did not change the
      depressive effect of strychnine on neuronal circuits. Our findings suggest that
      KCC2-dependent chloride homeostasis is mainly involved in GABA(A)R-mediated
      synaptic inhibition whereas GlyR-mediated tonic action plays a totally different
      role in regulating hippocampal circuit activity.

PMID- 16905251
TI  - Increased stress-induced analgesia in mice lacking the proneuropeptide convertase
      PC2.
AB  - Many neuropeptides involved in pain perception are generated by endoproteolytic
      cleavages of their precursor proteins by the proprotein convertases PC1 and PC2.
      To investigate the role of PC2 in nociception and analgesia, we tested wild-type
      and PC2-null mice for their responses to mechanical and thermal nociceptive
      stimuli, before and after a short swim in cold or warm water. Basal responses and
      responses after a cold swim were similar between the two groups. However, after a
      short forced swim in warm water, PC2-null mice were significantly less responsive
      to the stimuli than wild-type mice, an indication of increased opioid-mediated
      stress-induced analgesia. The enhanced analgesia in PC2-null mice may be caused
      by an accumulation of opioid precursor processing intermediates with potent
      analgesic effects, or by loss of anti-opioid peptides.

PMID- 16905252
TI  - Motor and cognitive improvement by deep brain stimulation in a transgenic rat
      model of Huntington's disease.
AB  - Altered activity of the globus pallidus externus (GPe) is responsible for at
      least part of the cognitive and motor symptoms of Huntington's disease (HD). In
      this study, we tested the hypothesis that bilateral globus pallidus (GP;
      equivalent of GPe in primates) deep brain stimulation (DBS) improves cognitive
      and motor symptoms in the first transgenic rat model of HD (tgHD rats). GP DBS
      with clinically relevant stimulation parameters resulted in a significant
      improvement of cognitive dysfunction and reduced the number of choreiform
      movements. This data indicate that GPe DBS can be used to treat cognitive and
      motor dysfunction in HD.

PMID- 16905253
TI  - Oligodendrocyte myelin glycoprotein (OMgp) in rat hippocampus is depleted by
      chronic ethanol consumption.
AB  - The hippocampal formation has been shown to be particularly vulnerable to the
      neurotoxic effects of chronic ethanol consumption. It was hypothesized that this
      damage was due to the disruption of the expression of neurotrophic factors and
      certain other proteins within the hippocampus. By using real-time reverse
      transcription-polymerase chain reaction (RT-PCR) techniques, this study aimed to
      determine whether chronic ethanol consumption could alter the mRNA expression
      level of brain-derived neurotrophic factor (BDNF), glial-derived neurotrophic
      factor (GDNF), and oligodendrocyte myelin glycoprotein (OMgp) in the hippocampus.
      Wistar male rats received an unrestricted access to a liquid diet containing 5%
      (v/v) ethanol as the sole source of fluid from 10 to 29 weeks of age. Control
      rats had unlimited access to a liquid diet containing an isocaloric amount of
      sucrose. We found that chronic ethanol consumption did not cause significant
      changes in the levels of mRNA for BDNF and GDNF. However, OMgp mRNA showed a
      significant deficit in ethanol-treated animals. It is suggested that this deficit
      may be related to the demyelination that is commonly observed in human alcoholics
      and that this may contribute to the functional and cognitive deficits.

PMID- 16905254
TI  - Acute exhaustive exercise does not alter lipid peroxidation levels and
      antioxidant enzyme activities in rat hippocampus, prefrontal cortex and striatum.
AB  - Although regular physical exercise is beneficial to the body, it is well known
      that exhaustive exercise causes oxidative stress in muscle. Recent studies
      suggest that regular moderate physical exercise has the beneficial effects on
      brain. However, there is little information regarding whether or not exhaustive
      exercise could generate oxidative stress in brain and the findings are
      conflicting. The aim of this study was to investigate the effects of exhaustive
      exercise on thiobarbituric acid reactive substances, as an indicator of lipid
      peroxidation, in the hippocampus, prefrontal cortex and striatum. Additionally we
      examined antioxidant enzymes activities, superoxide dismutase and glutathione
      peroxidase, to assess the effects of reactive oxygen species. Exhaustive exercise
      did not change superoxide dismutase and glutathione peroxidase enzyme activities
      and thiobarbituric acid reactive substances levels neither immediately (0 min)
      nor at 3, 6, 12, 24 and 48 h after the cessation of exercise in the brain. These
      results indicate that acute exhaustive exercise may not cause significant lipid
      peroxidation in the hippocampus, prefrontal cortex and striatum during the post
      exercise period.

PMID- 16905255
TI  - Long-term gliosis around chronically implanted platinum electrodes in the Rhesus
      macaque motor cortex.
AB  - Chronically implanted microelectrodes have been an important tool used by
      neuroscientists for many years and are critical for the development of neural
      prostheses designed to restore function after traumatic central nervous system
      (CNS) injury. It is well established that a variety of mammals, including non
      human primates (NHP), tolerate noble metal electrodes in the cortex for extended
      periods of time, but little is known about the long-term effects of electrode
      implantation at the cellular level. While data from rodents have clearly shown
      gliosis around such implants, there have been difficulties in demonstrating these
      reactions in NHP. Glial reactions are to be expected in NHP, since any trauma to
      the mammalian CNS is believed to result in the formation of a glial scar
      consisting of reactive astrocytes and microglia around the injury site. Because a
      glial scar can potentially affect the quality of recordings or stimulations from
      implanted electrodes, it is important to determine the extent of gliosis around
      implants in NHP. We studied the response of cortical glial cells to chronic
      electrode implantation in the motor cortices of Rhesus macaques (Macaca mulatta)
      after 3 months and 3 years duration. Antibodies specific for astrocytes and
      microglia were used to detect the presence of glial reactions around electrode
      implant sites. Reactive glia were found within the cortical neuropil surrounding
      the chronically implanted noble metal electrodes. Reactive gliosis persisted over
      the time periods studied and demonstrates the importance of developing strategies
      to minimize this event, even around noble metal implants.

PMID- 16905256
TI  - New variants in the CACNA1H gene identified in childhood absence epilepsy.
AB  - Childhood absence epilepsy (CAE) is a common form of idiopathic generalized
      epilepsy with polygenic inheritance. In our previous studies, relatively high
      frequent variants in the T-type calcium channel gene, CACNA1H, were identified in
      the Chinese Han population, most of which are located in exons 6-12. The goal of
      this study was to identify additional variants in this region of the CACNA1H
      gene. To this end, exons 6-12 were sequenced in 100 newly recruited CAE trios and
      191 normal controls. Thirty-nine variants were identified in CAE trios or
      controls, 14 of which were found only in CAE patients, including two
      nonsynonymous variants that were newly found. Thirteen of the 39 variants were
      found in both CAE patients and controls, 11 were found only in parents of CAE
      trios, and one was found only in controls. Twenty-eight of these variants had not
      been previously reported. Both permutation test and transmission/disequilibrium
      test (TDT) indicated that a SNP-52037C>T in intron11 was significant in
      association with CAE. In conclusion, these data further support the hypothesis
      that CACNA1H is an important susceptibility gene for CAE in the Chinese Han
      population.

PMID- 16905257
TI  - Extinction of conditioned eyeblink responses in patients with cerebellar
      disorders.
AB  - Extinction of conditioned eyeblink responses (CRs) was analyzed in sixteen
      patients with pure cortical cerebellar degeneration, 14 patients with lesions
      within the territory of the superior cerebellar artery (SCA), 13 patients with
      infarctions within the territory of the posterior inferior cerebellar artery
      (PICA) and 45 age-matched controls. Three-dimensional (3D) magnetic resonance
      (MRI) data sets were acquired in patients with focal lesions to identify affected
      cerebellar lobules and possible involvement of nuclei. Eyeblink conditioning was
      performed using a standard delay protocol. At the end of the experiment 10 CS
      alone trials were presented as extinction trials. Controls showed significant
      effects of extinction that is a significant decline comparing CR-incidences in
      the extinction trials and the last block of 10 trials of the paired trials. In
      the group of all cerebellar patients, however, no significant effects of
      extinction were observed. In patients with unilateral lesions effects of
      extinction were present on the unaffected, but not on the affected side. Deficits
      of extinction were observed in PICA and SCA patients both with and without
      involvement of cerebellar nuclei. Extending previous reports in cerebellar
      patients the present findings show that the ipsilateral cerebellar hemisphere
      contributes to extinction of conditioned eyeblink responses in humans. It cannot
      be ruled out, however, that impaired acquisition affected the extinction results.

PMID- 16905258
TI  - Stroboscopic image capture: reducing the dose per frame by a factor of 30 does
      not prevent beam-induced specimen movement in paraffin.
AB  - Beam-induced specimen movement may be the major factor that limits the quality of
      high-resolution images of organic specimens. One of the possible measures to
      improve the situation that was proposed by Henderson and Glaeser [Ultramicroscopy
      16 (1985) 139-150], which we refer to here as "stroboscopic image capture", is to
      divide the normal exposure into many successive frames, thus reducing the amount
      of electron exposure--and possibly the amount of beam-induced movement--per
      frame. The frames would then be aligned and summed. We have performed preliminary
      experiments on stroboscopic imaging using a 200-kV electron microscope that was
      equipped with a high dynamic range Charge-coupled device (CCD) camera for image
      recording and a liquid N2-cooled cryoholder. Single-layer paraffin crystals on
      carbon film were used as a test specimen. The ratio F(g)/F(0) of paraffin
      reflections, calculated from the images, serves as our criterion for the image
      quality. In the series that were evaluated, no significant improvement of the
      F(image)(g)/F(image)(0) ratio was found, even though the electron exposure per
      frame was reduced by a factor of 30. A frame-to-frame analysis of image
      distortions showed that considerable beam-induced movement had still occurred
      during each frame. In addition, the paraffin crystal lattice was observed to move
      relative to the supporting carbon film, a fact that cannot be explained as being
      an electron-optical effect caused by specimen charging. We conclude that a
      significant further reduction of the dose per frame (than was possible with this
      CCD detector) will be needed in order to test whether the frame-to-frame changes
      ultimately become small enough for stroboscopic image capture to show its
      potential.

PMID- 16905259
TI  - Giardia duodenalis and Cryptosporidium spp. in a veterinary college bovine
      teaching herd.
AB  - In a preliminary study, we commonly identified Giardia duodenalis in adult dairy
      cattle from a veterinary college teaching herd. Therefore, the present study was
      carried out in order to better understand the potential of adult cattle to act as
      a source for G. duodenalis infections for students and staff at the veterinary
      college. Fecal samples were collected bi-weekly from this herd of adult cattle
      (n=30) over an 8-month period to determine the prevalence of G. duodenalis and
      Cryptosporidium spp. within the herd. Nested PCR followed by DNA sequencing was
      then performed on a subset of positive samples in order to better understand the
      zoonotic potential of these infections. Every cow was sampled between 11 and 18
      times, depending on the date the animal joined the teaching herd. In total, 507
      fecal samples were collected from 30 different cows and examined for cysts and
      oocysts using epifluorescence microscopy. G. duodenalis prevalence during the
      course of the study ranged from 37% (11/30) to 64% (18/28), with a mean of 49%.
      Cumulative G. duodenalis prevalence was 73% (22/30). Zoonotic G. duodenalis
      assemblage A genotype was identified in 43% (6/14) of the G. duodenalis-positive
      samples on which PCR and genetic sequencing were successfully performed. G.
      duodenalis assemblage E was identified in 57% (8/14) of these samples.
      Cryptosporidium spp. oocysts were not detected in the feces of any cows during
      the study period. The presence of the zoonotic G. duodenalis assemblage A in 43%
      of the sequenced samples indicates that there is a potential risk of infection
      for students and staff at this research and teaching facility, although the roles
      of cows as sources of giardiasis in humans remain uncertain. Furthermore, due to
      the large amount of feces they produce, adult cattle may serve as important
      sources for G. duodenalis infections in young cattle, or other animals in the
      facility, despite relatively low numbers of cysts excreted per gram of feces. In
      contrast, the results of this study indicate that this herd posed a negligible
      risk of transmitting Cryptosporidium parvum infections to humans.

PMID- 16905261
TI  - An algorithm for the release of burn contractures of the extremities.
AB  - Burn contractures of the extremities present a clinical challenge. Flexion
      contractures are more common than extension contractures. The first component of
      treatment is adequate contracture release. A number of different methods are
      available for resurfacing the wound and these are reviewed. An algorithm is
      presented which permits a simple approach to managing burn scar contracture of
      the extremities.

PMID- 16905262
TI  - Progressive tissue injury in burns is reduced by rNAPc2.
AB  - INTRODUCTION: Burn wounds are characterised by central necrosis surrounded by an
      area of stasis with compromised perfusion. Secondary aggravation of the burn
      wound due to ischaemia in the zone of stasis can also result in necrosis. This
      study aims to improve circulation in the zone of stasis by reducing microthrombus
      formation and thereby to reduce secondary aggravation. MATERIAL AND METHODS:
      Recombinant nematode anticoagulant protein (rNAPc2) was administered to Wistar
      rats at 3 or 30 microg/kg as a single or daily dose. A comb pattern burn was
      induced on the dorsum of these rats and its evolution monitored by serial
      photography, planimetry, laser doppler flowmetry and immunohistochemistry.
      RESULTS: In the 30 microg/kg daily group, extension of the burn wound was curbed,
      limiting the burn area to 1.99+/-0.67 cm(2) on day 28, compared to 3.51+/-0.37
      cm(2) in the control group (p=0.015). Laser doppler evaluation showed a
      significant (p<0.001) increase in circulation in the first day post-burn.
      Significantly less (p<0.001) microvascular fibrin formation was observed by
      immunohistochemistry. CONCLUSION: Anticoagulation with rNAPc2 improved perfusion
      of the burn wound. The resultant reduction in the area of the burn led to earlier
      healing and less scar contracture.

PMID- 16905260
TI  - Antiproliferative and apoptosis inducing effect of lactoferrin and black tea
      polyphenol combination on hamster buccal pouch carcinogenesis.
AB  - Combination chemoprevention using tea polyphenols as one of the components has
      received growing consideration in recent years. The present study was designed to
      evaluate the antiproliferative and apoptosis inducing effects of bovine
      lactoferrin (bLF) and black tea polyphenol (Polyphenon-B: P-B) combination on
      7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP)
      carcinogenesis. Topical application of DMBA for 14 weeks induced buccal pouch
      tumours that showed aberrant expression of cytokeratins, a marker for epithelial
      carcinomas. This was associated with increased cell proliferation and evasion of
      apoptosis as revealed by upregulation of proliferating cell nuclear antigen, NF
      kappaB, mutant p53, Bcl-2 and downregulation of Bax, Fas and caspase 3 protein
      expression. Although dietary administration of bLF and Polyphenon-B alone
      significantly reduced tumour incidence, combined administration of bLF and
      Polyphenon-B was more effective in inhibiting HBP carcinogenesis by restoring
      normal cytokeratin expression, inhibiting cell proliferation and inducing
      apoptosis. These findings suggest that a "designer item" approach will be useful
      for human oral cancer prevention strategies.

PMID- 16905263
TI  - Explosive information on the internet.

PMID- 16905265
TI  - Use of power Doppler ultrasound to monitor renal perfusion during burn shock.
AB  - BACKGROUND: Renal cortical blood flow can be quantified by means of power Doppler
      ultrasound (PDUS) image analysis. We hypothesized that renal cortical perfusion,
      estimated by PDUS image intensity (PDUSII), would decrease during burn shock and
      improve during resuscitation in a porcine model. METHODS: Eight anesthetized
      swine sustained a 75% scald injury. Resuscitation began 6h postburn. Renal
      cortical blood flow was measured directly using fluorescent microspheres
      (CORFLO), and was estimated noninvasively by PDUSII. PDUSII, CORFLO, and
      cardiopulmonary data were recorded every 2h. RESULTS: PDUSII decreased
      significantly from preburn to postburn hour 6, and increased with resuscitation
      by hour 8. CORFLO correlated well with PDUS image intensity (n=48, r(2)=0.696)
      but poorly with urine output (n=48, r(2)=0.252). CONCLUSION: PDUS in this study
      was superior to the urine output in assessing renal cortical microvascular blood
      flow during shock and resuscitation, and may be useful in the care of injured
      patients.

PMID- 16905266
TI  - Effects of neonatal handling on the basal forebrain cholinergic system of adult
      male and female rats.
AB  - Neonatal handling is an early experience which results in improved function of
      the hypothalamic-pituitary-adrenal axis, increased adaptability and coping as a
      response to stress, as well as better cognitive abilities. In the present study,
      we investigated the effect of neonatal handling on the basal forebrain
      cholinergic system, since this system is known to play an important role in
      cognitive processes. We report that neonatal handling results in increased number
      of choline-acetyl transferase immunopositive cells in the septum/diagonal band,
      in both sexes, while no such effect was observed in the other cholinergic nuclei,
      such as the magnocellular preoptic nucleus and the nucleus basalis of Meynert. In
      addition, neonatal handling resulted in increased M1 and M2 muscarinic receptor
      binding sites in the cingulate and piriform cortex of both male and female rats.
      A handling-induced increase in M1 muscarinic receptor binding sites was also
      observed in the CA3 and CA4 (fields 3 and 4 of Ammon's horn) areas of the
      hippocampus. Furthermore, a handling-induced increase in acetylcholinesterase
      staining was found only in the hippocampus of females. Our results thus show that
      neonatal handling acts in a sexually dimorphic manner on one of the cholinergic
      parameters, and has a beneficial effect on BFCS function, which could be related
      to the more efficient and adaptive stress response and the superior cognitive
      abilities of handled animals.

PMID- 16905264
TI  - Histology of the thick scar on the female, red Duroc pig: final similarities to
      human hypertrophic scar.
AB  - The etiology and treatment of hypertrophic scar remain puzzles even after decades
      of research. A significant reason is the lack of an accepted animal model of the
      process. The female, red Duroc pig model was described long ago. Since the skin
      of the pig is similar to that of humans, we are attempting to validate this model
      and found it to be encouraging. In this project we quantified myofibroblasts,
      mast cells and collagen nodules in the thick scar of the Duroc pig and compared
      these to the values for human hypertrophic scar. We found the results to be quite
      similar and so further validated the model. In addition, we observed that soon
      after wounding an inflammatory cell layer forms. The thickness of the
      inflammatory layer approaches the thickness of the skin removed as if the
      remaining dermis "knows" how much dermis is gone. In deep wounds this
      inflammatory layer thickens and this thickness is predictive of the thickness of
      the ultimate scar.

PMID- 16905267
TI  - Acetylcholinesterase inhibitor acting on the brain improves detrusor overactivity
      caused by cerebral infarction in rats.
AB  - PURPOSE: The functional contribution of the cholinergic pathway in the frontal
      cortex to micturition was evaluated following cerebral ischemia. Furthermore, it
      was examined whether reactivation of this regulatory system using
      acetylcholinesterase inhibitor could improve detrusor overactivity. METHODS: Left
      middle cerebral artery occlusion (MCAO) was performed in female Sprague-Dawley
      rats. Choline acetyltransferase (ChAT) activities after MCAO were assayed to
      assess the damage to cholinergic neurons. ChAT activities in the bilateral
      cortex, hippocampus, and pons were calculated by measuring the conversion of 1
      [14C] acetyl-coenzyme A to [14C] acetylcholine. Effects on cystometrography of
      i.v. or i.c.v. donepezil hydrochloride (DON), a centrally acting
      acetylcholinesterase inhibitor, were investigated in conscious sham-operated (SO)
      and cerebral infarcted (CI) rats. To investigate whether DON in the forebrain was
      affected, we decerebrated rats after CI or SO, and investigated the effects on
      cystometrography of i.v. DON. RESULTS: Bladder capacity was markedly decreased
      after MCAO, and remained below half of the pre-occlusion capacity. The greatest
      increase in bladder capacity was attained at 1.2 x 10(-2) nM/kg of DON given
      i.v., with a change of 52.8% (P < 0.05). In cases of i.c.v. DON, the greatest
      increase in bladder capacity was at the dose of 6 x 10(-2) pmol with the change
      of 95.8% (P < 0.01). The activity of ChAT was decreased in the left cortex and
      hippocampus 24 h after MCAO (P < 0.05). In decerebrated rats, low dose of DON did
      not change micturition parameters. CONCLUSIONS: These results suggest that by
      upregulation of the forebrain muscarinic inhibitory mechanism,
      acetylcholinesterase inhibitor improves detrusor overactivity by cerebral
      infarction.

PMID- 16905268
TI  - Postnatal nicotine and/or intermittent hypercapnic hypoxia effects on apoptotic
      markers in the developing piglet brainstem medulla.
AB  - The most important risk factors currently identified for the sudden infant death
      syndrome (SIDS) are prone sleeping and cigarette smoke exposure. In this study,
      we investigated the neuropathological sequelae of these risk factors by exposing
      piglets to intermittent hypercapnic-hypoxia (IHH) and/or nicotine (nic) in the
      early postnatal period. Our hypothesis was that either nic or IHH exposure could
      increase neuronal cell death, and that combined exposure (nic+IHH) would be
      additive. Four exposure patterns were studied: controls (n=14), IHH (n=10), nic
      (n=14), and nic+IHH (n=14). All groups had equal gender ratios. Nic exposure via
      an implanted osmotic minipump commenced within 48 h of birth and continued until
      age 13-14 days when animals were killed and brains collected. A total of 48 min
      of hypercapnic-hypoxia was delivered on the day immediately prior to killing in a
      pattern comprising 6 min of HH (8% O(2), 7% CO(2), balance N(2)) alternating with
      6 min of air. Immunohistochemistry was performed to identify neurons positive for
      active caspase-3 and DNA fragmentation (terminal deoxynucleotidyl transferase
      mediated dUTP nick-end labeling, TUNEL) in seven nuclei of the caudal medulla.
      Staining quantification showed that: 1. IHH induced neuronal death (increased
      both TUNEL and casapse-3) in more brainstem nuclei than nicotine. 2. Females were
      more severely affected by IHH than males. 3. Where IHH and nicotine were
      combined, TUNEL expression was approximately 5% less than IHH alone, but changes
      in caspase-3 were variable. We conclude that acute exposure to IHH in the
      postnatal period is more neurotoxic than exposure to nicotine alone. Combined
      exposure to IHH and nicotine produced variable responses with some results
      suggesting that nicotine can be neuroprotective. These results indicate that
      environmental insults attributable to prone sleeping can produce neurotoxic
      sequelae in SIDS, with some regional specificity in the response. However, no
      consistent relationship is evident when combining the two insults.

PMID- 16905270
TI  - Differentially expressed genes in the rat cochlear nucleus.
AB  - The cochlear nucleus is the first central pathway involved in the processing of
      peripheral auditory activity. The anterior ventral cochlear nucleus (AVCN),
      posterior ventral cochlear nucleus (PVCN) and dorsal cochlear nucleus (DCN) each
      contain predominant populations of neurons that have been well characterized
      regarding their morphological and electrophysiological properties. Little is
      known, however, of the underlying genetic factors that contribute to these
      properties and the initial steps in auditory processing. Serial analysis of gene
      expression (SAGE), supported by microarray experiments, was performed on each
      subdivision of the rat cochlear nucleus to identify genes that may sub-serve
      specialized roles in the central auditory system. Pair-wise comparisons between
      SAGE libraries from the AVCN, PVCN and DCN were correlated with microarray
      experiments to identify individual transcripts with significant differential
      expression. Twelve highly correlated genes were identified representing
      cytoskeletal, vesicular, metabolic and g-protein regulating proteins. Among these
      were Rgs4 which showed higher expression in the DCN, Sst and Cyp11b1 with very
      high expression in the AVCN and Calb2 with preferential expression in the PVCN.
      The differential expression of these genes was validated with real-time reverse
      transcriptase-polymerase chain reaction. These experiments provide a basis for
      understanding normal auditory processing on a molecular level and a template for
      investigating changes that may occur in the cochlear nucleus with hearing loss,
      the generation and percept of tinnitus, and central auditory processing
      disorders.

PMID- 16905269
TI  - P2 purinergic receptors signal to STAT3 in astrocytes: Difference in STAT3
      responses to P2Y and P2X receptor activation.
AB  - Extracellular ATP, released upon tissue damage to the CNS, can evoke reactive
      astrogliosis. The released ATP activates P2 purinergic receptors associated with
      the proliferation of normally quiescent astrocytes, although the underlying
      mechanisms remain to be fully elucidated. Signal transducer and activator of
      transcription 3 (STAT3) has been implicated in reactive astrogliosis and plays an
      important role in cell cycle regulation. Therefore, we investigated whether
      extracellular ATP and purinergic receptors regulate STAT3 signaling. Using
      immunoblot analysis, we found that addition of ATP to primary cultures of rat
      cortical astrocytes increased Ser-727 phosphorylation of STAT3 in a time
      sensitive and concentration-dependent manner. ATP-stimulated Ser-727 STAT3
      phosphorylation was mediated through P2 receptor activation since suramin, an
      antagonist of P2 receptors, diminished this response, whereas 8-(para-sulfo
      phenyl)-theophylline (8PSTP), an antagonist of P1 receptors, did not. We found
      that UTP, an agonist of P2Y(2/4/6) receptors, stimulated rapid and robust
      phosphorylation of Ser727-STAT3, whereas BzATP, an agonist for P2X receptors,
      exhibited a delayed and weaker response. In contrast, both P2Y and P2X agonists
      stimulated phosphorylation of Tyr705-STAT3 to a similar extent. P2 receptors can
      couple to extracellular signal-regulated protein kinases (ERK) and we found that
      inhibition of ERK signaling blocked phosphorylation of Ser727-STAT3. Further
      characterization of the Ser727-STAT3 phosphorylation response to P2Y receptor
      activation supported a role for P2Y2 and P2Y4, but not P2Y6, receptors as well as
      a partial role for P2Y1 receptors. Because phosphorylation of Ser727-STAT3 can
      promote DNA transcriptional activity of cell cycle regulatory genes, the
      differences in phosphorylation of Ser727-STAT3 may contribute to the mechanism by
      which P2Y receptors promote, whereas P2X receptors inhibit, astrocyte
      proliferation. In support of this hypothesis, inhibition of STAT3 activation by
      cucurbitacin I prevented ATP-stimulated mitogenesis. We conclude that P2
      receptors stimulate STAT3 activation and suggest that P2 receptor/STAT3 signaling
      may play an important role in astrocyte proliferation and reactive astrogliosis.

PMID- 16905271
TI  - Dopamine D1 receptors co-distribute with N-methyl-D-aspartic acid type-1 subunits
      and modulate synaptically-evoked N-methyl-D-aspartic acid currents in rat
      basolateral amygdala.
AB  - Activation of dopamine D1 or glutamate, N-methyl-d-aspartic acid (NMDA) receptors
      in the basolateral amygdala (BLA) can potently influence affective behaviors and
      associative learning. Physical protein-protein interactions also can occur
      between C-terminal peptides of D1 receptors and the NMDA-receptor subunit-1
      (NR1), suggesting intracellular associations of direct relevance to dopaminergic
      modulation of NMDA currents. We examined this possibility by combining electron
      microscopic immunolabeling of the D1 and NR1 C-terminal peptides with in vitro
      patch-clamp recording in the rat BLA. In the in vivo preparations, D1 and NR1
      were localized to the surface or endomembranes of many of the same somata and
      dendrites as well as a few axon terminals, including those forming asymmetric,
      excitatory-type synapses. In vitro analysis of physiologically characterized
      projection neurons revealed an excitatory response to bath application of either
      dopamine or the preferential D1 receptor agonist, dihydrexidine. In these
      neurons, dopamine also selectively reduced stimulation-evoked isolated NMDA
      receptor-mediated currents, but not isolated non-NMDA receptor-mediated currents
      or the response to exogenous NMDA application. The selective reduction of the
      NMDA receptor-mediated currents suggests that this effect occurs at a
      postsynaptic locus. Moreover, both D1 and NR1 were localized to postsynaptic
      surfaces of biocytin-filled and physiologically characterized projection neurons.
      Our results provide ultrastructural evidence for D1/NR1 endomembrane associations
      that may dynamically contribute to the attenuation of NMDA receptor-mediated
      currents following prior activation of D1 receptors in BLA projection neurons.
      The potential for postsynaptic cross-talk between D1 and NMDA receptors in BLA
      projection neurons as well as a similar interaction in presynaptic terminals
      could have important implications for the formation and extinction of affective
      memories.

PMID- 16905272
TI  - Intraductal trastuzumab treatment may be effective in the management of ductal
      carcinoma in situ of the breast with HER-2 overexpression.

PMID- 16905273
TI  - Perifosine may be of therapeutic usefulness in morbid obese females via
      inhibition of the PI3K/Akt signaling pathway.

PMID- 16905274
TI  - TrkB partial agonists: potential treatment strategy for major depression.
AB  - Brain-derived neurotrophic factor (BDNF) regulates a wide variety of processes in
      the nervous system, including neural development, function and survival, through
      activation of the tyrosine kinase B receptor (TrkB). Evidence suggests that low
      central BDNF activity, especially in the hippocampus, may play a pivotal role in
      the pathophysiology of major depression, and that agents that can increase BDNF
      TrkB pathway signaling may be therapeutic for this disease. However, recent
      studies showed that increased BDNF activity in the mesolimbic region may cause a
      depressed state. A partial agonist is an agent that elicits a maximum response
      that is less than that of an agonist and acts as an antagonist in the presence of
      excess full agonist. Recently some small peptides have been synthesized that act
      as TrkB partial agonists. Since BDNF might be pro-depressive in the mesolimbic
      system and anti-depressive in the hippocampus region, it is proposed that these
      peptides or other partial TrkB agonists may provide a novel strategy for the
      treatment of major depression, which may be associated with BDNF-TrkB
      hypofunction in hippocampus and/or hyperfunction in the mesolimbic system.
      Furthermore, given the potential imbalance of BDNF in specific brain regions in
      major depression, selection of agents with maximal hippocampus/mesolimbic BDNF
      activation ratio could be of importance in the development of novel
      antidepressants.

PMID- 16905275
TI  - Cancer and sleep apnea--the hypoxia connection.

PMID- 16905276
TI  - Antihyperglycemic effect of Cucurbita ficifolia fruit extract in streptozotocin
      induced diabetic rats.
AB  - In the present study, the antihyperglycemic effects of Cucurbita ficifolia fruit
      extract were investigated on streptozotocin-induced experimental diabetes in
      rats. Oral administration of the extract (300 and 600 mg/kg body weight, day) for
      30 days resulted in a significant reduction in blood glucose, glycosylated
      haemoglobin, and an increase in plasma insulin and total haemoglobin. The effect
      was compared with 150 mg/kg b.w. tolbutamide.

PMID- 16905277
TI  - Hypoglycemic and hypocholesterolemic activities of the aqueous leaf and seed
      extract of Phyllanthus amarus in mice.
AB  - The effect of the aqueous leaf and seed extracts of Phyllanthus amarus at oral
      dose of 150, 300 and 600 mg/kg was investigated for their antidiabetic and anti
      lipidemic potentials. The extract produced a dose-dependent decrease in the
      fasting plasma glucose and cholesterol, and reduction in weights in treated mice.
      The results suggest that the extract could be enhancing peripheral utilization of
      glucose but the mechanisms on how this works remain unclear.

PMID- 16905278
TI  - A new phenolic glycoside from Paeonia lactiflora.
AB  - A new phenolic glycoside , 2-methoxy-5-(E)-propenyl-phenol-beta-vicianoside, was
      isolated from the root of Paeonia lactiflora. The structure of the new glycoside
      was elucidated by chemical and spectroscopic methods.

PMID- 16905279
TI  - Antidiabetic activity of Caesalpinia bonducella seed extracts in rats.
AB  - The seed extracts of Caesalpinia bonducella were subjected to screening of
      antidiabetic activity in alloxan induced hyperglycemia. The oral administration
      of the extracts (300 mg/kg) produced significant antihyperglycemic action as well
      as it lowered the BUN levels significantly. In the same study the action of the
      extracts on diabetes induced hyperlipidemia was analyzed where the extracts
      significantly lowered the elevated cholesterol as well as LDL level. The
      antihyperglycemic action of the extracts may be due to the blocking of glucose
      absorption. The drug has the potential to act as antidiabetic as well as
      antihyperlipidemic.

PMID- 16905280
TI  - Common genomic structure for the Lepidoptera cadherin-like genes.
AB  - A cadherin-like protein present in the midgut epithelial cells of Lepidoptera is
      associated with insect resistance to Bacillus thuringiensis Cry toxins. We
      describe for the first time the genes that encode the cadherin-like proteins in
      Ostrinia nubilalis, Helicoverpa armigera, and Bombyx mori, and analyze their
      organization. These genes encompass 19.6 kb, 20.0 kb, and 41.8 kb of genomic DNA,
      respectively, and despite the size heterogeneity, they are all composed of 35
      exons that are linked by 34 introns. In contrast to the high variability noted
      for the sizes of the introns, the sizes of the coding exons were almost
      completely preserved among the three species, because the intronic sequences
      (except the first and last one) were inserted in homologous positions in the
      respective cDNA sequences. In all cases, the first intron (the longest one) was
      located in the 5'-untranslated region. These results point out a highly conserved
      structure that indicates that these genes are orthologous. Analysis of the gene
      sequences showed a common GC-rich region located in exon 31 and several tandem
      repeats that were specific for each gene. Partial sequences from transposable
      elements were found only in B. mori and accounted, in part, for the large size of
      the insect gene. The in silico analysis of the protein products of these genes
      showed a common structure and grouped these proteins into the protocadherin
      family.

PMID- 16905281
TI  - Do we neglect women with sleep apnea?
AB  - Obstructive sleep apnea (OSA) affects approximately 5% of women and 15% of men in
      the middle-aged adults, and associated with adverse health outcomes. The
      prevalence and severity of OSA in women increase across the menopause, as the
      cardiovascular death and events do. Unfortunately, women with OSA might be under
      diagnosed due to circumstances related to the family lifestyle and socio-cultural
      factors in addition to the different OSA clinical expression. Evaluation of
      cardiovascular global risk assessment in women with OSA is very important to
      prevent the high potential cardiovascular morbidity and mortality, since they are
      poorly informed about cardiovascular disease (CVD). So, we should be aware of the
      clues suspecting OSA and cardiovascular risk in women admitting to sleep clinics.

PMID- 16905282
TI  - Bioavailability of salvianolic acid B in conscious and freely moving rats.
AB  - Salvianolic acid B is an herbal ingredient isolated from Salvia miltiorrhiza. The
      aim of this study was to apply an automated blood sampling system coupled to a
      simple liquid chromatographic system to determine the bioavailability of
      salvianolic acid B in stress-free rats. The plasma sample (25 microl) was vortex
      mixed with 50 microl of internal standard solution (chloramphenicol 10 microg/ml
      in acetonitrile) to achieve protein precipitation. Salvianolic acid B in the rat
      plasma was separated using a reversed-phase C18 column (250 mm x 4.6 mm, 5
      microm) with a mobile phase of acetonitrile-methanol-20mM NaH(2)PO(4) (adjusted
      to pH 3.5 with H(3)PO(4)) (20:10:70 v/v/v) containing 0.1mM 1-octanesulfonic
      acid, and the flow-rate of 1 ml/min. The UV detection wavelength was 286 nm. The
      concentration-response relationship from the present method indicated linearity
      over a concentration range of 0.5-200 microg/ml. Intra- and inter-assay precision
      and accuracy of salvianolic acid B fell well within the predefined limits of
      acceptability (<15%). The plasma sample of salvianolic acid B was further
      identified by LC-MS/MS in the negative ion mode using mass transition m/z 358.2
      to the product ion m/z 196.9. After salvianolic acid B (100mg/kg, i.v.; 500
      mg/kg, p.o.) was given in conscious and freely moving rats, the AUC were 5030+/
      565 and 582+/-222 min microg/ml for intravenous (100 mg/kg) and oral (500 mg/kg)
      doses, respectively. The oral bioavailability of salvianolic acid B in freely
      moving rats was calculated to be 2.3%.

PMID- 16905283
TI  - The appropriate use of subpopulation corrections for differences in endogamous
      communities.
AB  - Zhivotovsky et al. [L.A. Zhivotovsky, S. Ahmed, W. Wang, A. Bittles, The forensic
      DNA implications of genetic differentiation between endogamous communities,
      Forensic Sci. Int. 119 (2001) 269-272] gave an estimate of 0.13 for the
      coancestry coefficient, theta in three co-resident Pakistani communities. Wang et
      al. [W. Wang, S.G. Sullivan, S. Ahmed, D. Chandler, L.A. Zhivotovsky, A.H.
      Bittles, A genome-based study of consanguinity in three co-resident endogamous
      Pakistan communities, Ann. Hum. Genet. 94 (2000) 41-49] explain that the sampling
      is from extended families but conclude that "the present findings show that
      differentiation resulting from genetic stratification by genetic relatedness can
      be very pronounced in specific populations and thus be important in the
      evaluation of forensic DNA evidence." In this paper we present simulation results
      that show that sampling from families will be expected to produce high values of
      theta regardless of the population value for theta. A theta value estimated in
      this way cannot be used in formulae suggested by NRC II [NRC II, National
      Research Council Committee on DNA Forensic Science, The Evaluation of Forensic
      DNA Evidence, National Academy Press, Washington, DC, 1996] (Eqs. (1) and (2)) to
      estimate the match probability for a DNA profile in a subpopulation. Whilst it
      may have some application to estimating the match probability from the pedigree
      itself there are superior methods for assigning match probabilities for
      relatives.

PMID- 16905284
TI  - Laryngeal carcinoma presenting as a large anterior neck abscess.
AB  - Laryngeal carcinoma presenting as a cervical abscess is rare, so that its
      diagnosis is not easy. We described a case of laryngeal squamous cell carcinoma
      presenting as a prelaryngeal large abscess. Markedly swollen false vocal fold
      inhibited fiberscopic examination of the vocal folds. CT scan indicated
      destruction of the thyroid cartilage. Although biopsies from the abscess did not
      reveal malignancy, laryngeal squamous cell carcinoma was confirmed by
      laryngomicrosurgery with laryngeal vestibulectomy. The patient was treated by
      total laryngectomy with neck dissection followed by radiotherapy. The abscess was
      thought to be formed not by direct extension and necrosis of the tumor, but by
      the leakage of air and mucus through the fistula on the destroyed thyroid
      cartilage. Precise observation and biopsy under directscopic vestibulectomy
      played an important role in diagnosis of malignancy inherent in severe
      inflammatory tissues.

PMID- 16905285
TI  - Storage of the incus in the mastoid bowl for use as a columella in staged
      tympanoplasty.
AB  - OBJECTIVE: To evaluate whether the incus of the cholesteatomatous ear preserved
      in the mastoid bowl during the first stage of planned two-stage tympanoplasty can
      tolerate long-term implantation and be used in ossicular reconstruction during
      the second stage. METHODS: The study group included 24 ears of 23 patients who
      underwent staged tympanoplasty for the treatment of middle ear cholesteatoma. At
      the first stage, after removing the incus to eradicate the middle ear disease, it
      was returned to the mastoid bowl and stored there until use at the second stage.
      The average interval between the two stages was 8.3 months (range 6-12 months).
      RESULTS: The incus was identified in all cases at the second stage: 10 incudes
      were found to be covered with a thin mucosa layer, 12 were buried in fibrous or
      granulation tissue, and 2 were joined to the surrounding bone. Residual
      cholesteatoma was found in six ears, either in the attic (three ears) or tympanic
      sinus (three ears). It never occurred in the mastoid bowl where the incus had
      been preserved. In 19 cases, the incus was available as a short columella for
      ossicular reconstruction. The remaining five cases were reconstructed using a
      hydroxyapatite ossicle as a long columella, since the stapes superstructure was
      missing at the second stage. In one case, the stored incus underwent remarkable
      absorption between stages. CONCLUSION: Preservation of the incus in the mastoid
      bowl is an effective option in planned two-stage tympanoplasty, when the incus is
      considered useful for ossicular reconstruction at the second stage.

PMID- 16905286
TI  - [Role of the expert when communicating during an epidemiological alert: ethical
      issues].

PMID- 16905287
TI  - Decrease in the lgl tumor suppressor dose in Drosophila increases survival and
      longevity in stress conditions.
AB  - Recent studies suggest that downregulation of tumor suppressor genes might not
      only favor cancer development but also postpone organisms' aging and increase
      longevity. However, there is lack of population-based studies directly supporting
      this idea. We studied the lgl lethal alleles which are widespread in natural
      Drosophila populations. We demonstrate, for the first time, that animals
      heterozygous on the loss-of-function lgl tumor suppressor gene display a clear
      pre-adult viability advantage under stressful conditions (high 29 degrees C and
      low 16 degrees C temperatures). We found also the survival and longevity
      advantage effect of the lgl loss-of-function in the temperature stress
      conditions. The main features of this longevity influence are following. First,
      the lgl-dependent life span increase is sex-dependent; in all experimental
      combinations males are more sensitive than females of relevant genotypes. Second,
      the effect is stronger under the life-shortening temperature stress, 29 degrees
      C, where the hormesis was demonstrated. Third, the favoring effect of reduced
      dosage of tumor suppressor displays clearly in old but not young animals,
      delaying aging. Forth, the maternal or epigenetic inheritance of thermotolerance
      from mother to offspring appears to strengthen the observed longevity effects.
      One possible explanation of this stress-adaptive effect of reduced tumor
      suppressor dose might be a better resistance of Drosophila post-mitotic cells to
      a stress-associated apoptosis at old ages.

PMID- 16905288
TI  - Exotic flora dependence of an unusual Brazilian propolis: the pinocembrin
      biomarker by capillary techniques.
AB  - Significant amounts of pinocembrin (>10%), a dihydroxy-flavanone, was found in
      the composition of an unusual brand of a subtropical Brazilian propolis.
      Incidentally, this sealing material was obtained from hives surrounding a large
      forestry site based on a single exotic flora, namely poplar (Populus sp.).
      Examination of the different botanical parts of poplar revealed the buds as the
      main source of the flavanone. Techniques used for the establishment of the
      chemical correlation between the propolis brand and the poplar buds were
      TLC/densitometry, capillary GC-MS in the e.i. mode, and CZE with DAD monitoring.
      Since color enhancement after Al3+ complexation applies just for more
      hydroxylated flavonoids, the alternative techniques herein applied were of value
      for pinocembrin detection and estimation. Analytical data indicated the dominance
      of the main phenolic pinocembrin biomarker as well as the presence of other
      related flavonoids in the botanical source and in the propolis derived thereof.

PMID- 16905289
TI  - Cloning and functional characterization of allelic variation in the porcine
      prolactin receptor.
AB  - Prolactin (PRL) regulates various functions in pigs including reproduction,
      mammary development and lactation. We used 5'-rapid amplification of cDNA ends
      (5'-RACE) to clone three full-length alleles of the porcine PRL receptor (pPRLR)
      from Landrace (alleles LR2 and LR4) and Yucatan miniature (MP) pigs,
      corresponding to the A and B alleles previously reported to be associated with
      reproductive traits. When expressed in Chinese hamster ovary (CHO-K1) cells, all
      three pPRLRs transduced differentiation signals to a beta-casein promoter with
      the same effectiveness, where human growth hormone (hGH) and porcine PRL (pPRL)
      were more effective ligands than ovine PRL (oPRL). The pPRLR had a lower binding
      affinity for oPRL than pPRL while binding affinity for hGH was not different
      between the three pPRLR variants. The pPRLRs primarily localized to the cytoplasm
      with perinuclear concentration. In conclusion, we have cloned three allelic
      variants of the pPRLR and have functionally characterized these as different from
      the hPRLR. However, our data do not support the proposal that allelic variation
      of the pPRLR confers functional differences in vivo.

PMID- 16905290
TI  - Thyroid nodule evaluation: what have we really learned from recent clinical
      guidelines?
AB  - Recent guidelines for the evaluation of thyroid nodules clarify the diagnostic
      algorithm while also reporting important differences. The performance of fine
      needle aspiration (FNA) for cytological examination follows serum TSH
      determination and thyroid ultrasonography. Thyroid scintigraphy is recommended
      following a low TSH value and/or FNA yielding an indeterminate follicular
      cytology. The use of thyroid ultrasonography is the source of some controversy:
      though it is recommended as a principal first test, its real-time use to guide
      FNA ranges from routine to only following an FNA yielding an inadequate or
      nondiagnostic cytological result. In clinical practice, the proportion of
      physicians utilizing ultrasonography, scintigraphy and FNA varies and frequently
      deviates from recommended guidelines. The development of guidelines is necessary
      to bring about consistency and optimization to the diagnostic work-up of thyroid
      nodules. It is likely that novel diagnostic procedures, such as molecular
      markers, large needle aspiration biopsy and thyroid imaging with tracers beyond
      conventional radioactive iodine or (99m)Tc pertechnetate, will lead to improved
      performance and implementation of guidelines.

PMID- 16905291
TI  - MDMA administration to pregnant Sprague-Dawley rats results in its passage to the
      fetal compartment.
AB  - Recent investigations have demonstrated that prenatal 3,4
      methylenedeoxymethamphetamine (MDMA; ecstasy) exposure in rats results in
      significant and persistent changes in the developing brain. However, no published
      pharmacokinetic studies exist demonstrating that MDMA administered during
      pregnancy passes to the fetal compartment. This leaves open the question whether
      MDMA is directly acting on the fetal brain to produce the observed changes in
      previous studies, or whether such effects are an indirect result of MDMA
      administration to the pregnant dam. Therefore, pregnant rats were administered a
      single dose of MDMA (15 mg/kg, subcutaneous) at embryonic day 14 (E14) and the
      levels of MDMA and its metabolite 3,4-methylenedioxyamphetamine (MDA) were
      quantified in maternal plasma, amniotic fluid, and fetal brain over 8 h by HPLC.
      The time course of MDMA and MDA metabolism was reliable and reproducible in all
      tissues. There was a strong correlation between fetal amniotic fluid and fetal
      brain suggesting that amniotic fluid could be used to reliably estimate fetal
      brain levels without directly utilizing fetal brain tissue. These data also
      provide a framework for subsequent in vitro cell culture studies using
      biologically relevant MDMA doses.

PMID- 16905292
TI  - Short-term effects of endotracheal intubation on voice.
AB  - The objective of this study was to examine the vocal symptoms and acoustic
      changes perceived in the short period after endotracheal intubation, and to find
      the association between these changes and the endotracheal tube parameters. A
      total of 35 subjects were included. They were examined preoperatively, and 2 and
      24 hours postoperatively. The vocal symptoms of hoarseness, vocal fatigue, loss
      of voice, throat clearing, globus pharyngeus, throat pain, and the acoustic
      variables mainly average fundamental frequency, relative average perturbation,
      shimmer, noise to harmony ratio, voice turbulence index, habitual pitch, and
      maximum phonation time (MPT) were assessed as such and in relation to the
      following endotracheal tube parameters: duration of anesthesia, number of
      intubation attempts, size of the tube, cuff volume, cuff mean pressure, and the
      emergence. The association between anesthesia parameters with incidence of vocal
      complaints and changes in acoustic parameters were examined using logistic and
      linear regression. Vocal fatigue was associated significantly with the increase
      in cuff volume and the number of intubation attempts. Throat clearing was
      associated significantly with the increase in cuff mean pressure. Only the
      increase in habitual pitch was associated significantly with the increase in cuff
      volume. The acute short-term effect of endotracheal intubation on voice is
      significant. The most important endotracheal tube parameters that affect the
      vocal changes are the cuff mean pressure and volume. The laryngeal contribution
      to these vocal changes seems to be minimal. All vocal symptoms increased
      significantly except for globus pharyngeus at 2 hours postoperatively. The
      acoustic parameters did not change significantly except for a decrease in MPT. At
      24 hours postoperatively, all vocal symptoms subsided with no significant
      difference to baseline value. The habitual pitch increased significantly, and the
      rest of the parameters remained comparable to baseline value.

PMID- 16905294
TI  - The incidence of schizophrenia in European immigrants to Canada.
AB  - OBJECTIVE: The risk for schizophrenia in immigrants to Europe is approximately
      three times that of native-born populations. Discrimination and marginalization
      may influence the risk for schizophrenia within migrant populations. The primary
      objective of the present study was to determine whether the risk associated with
      migration was also evident 100 years ago. A second objective was to determine
      whether changing social stresses are associated with changes to the incidence of
      schizophrenia. METHOD: During the first two decades of the twentieth century, the
      Provincial Mental Hospital was the sole provider of psychiatric services in
      British Columbia, Canada. Detailed clinical records have been preserved for 99.5%
      of 2477 patients who had a psychiatric admission between 1902 and 1913. Diagnoses
      were made after a detailed file review and 807 patients met DSM-IV criteria for
      first-episode schizophrenia, schizophreniform disorder, schizoaffective disorder,
      or psychosis not otherwise specified. Diagnoses had high inter-rater reliability.
      The incidence of schizophrenia in migrants from Britain or Continental Europe was
      compared with that in the Canadian-born population using indirect standardization
      and Poisson models. RESULTS: Migration from Britain or Continental Europe to
      Canada in the early twentieth century was associated with an increased rate of
      schizophrenia; IRR=1.54, (95% CI=1.33-1.78). Incidence increased over time in
      immigrants but not in the native-born population and this increase occurred
      during a period of economic recession. CONCLUSIONS: Migration was a risk factor
      for schizophrenia a century ago as it is today. This risk occurred in white
      migrants from Europe and increased during a period of increased social stress.

PMID- 16905293
TI  - Dynamic biomechanical strain inhibits IL-1beta-induced inflammation in vocal fold
      fibroblasts.
AB  - Despite the fact that vocal folds are subjected to extensive mechanical forces,
      the role of mechanical strain in vocal fold wound healing has been overlooked.
      Recent studies on other tissues have demonstrated that low physiological levels
      of mechanical forces are beneficial to injured tissues, reduce inflammation, and
      induce synthesis of matrix-associated proteins essential for enhanced wound
      healing. In this study, we speculated that mechanical strain of low magnitudes
      also attenuates the production of inflammatory mediators and alters the
      extracellular matrix synthesis to augment wound healing in cultured vocal fold
      fibroblasts. To test this hypothesis, fibroblasts from rabbit vocal folds were
      isolated and exposed to various magnitudes of cyclic tensile strain (CTS) in the
      presence or absence of interleukin-1beta (IL-1beta). Results suggest that IL
      1beta activates proinflammatory gene transcription in vocal fold fibroblasts.
      Furthermore, CTS abrogates the IL-1beta-induced proinflammatory gene induction in
      a magnitude-dependent manner. In addition, CTS blocks IL-1beta-mediated
      inhibition of collagen type I synthesis, and thereby upregulates collagen
      synthesis in the presence of IL-1beta. These findings are the first to reveal the
      potential utility of low levels of mechanical signals in vocal fold wound
      healing, and support the emerging on vivo data suggesting beneficial effects of
      vocal exercise on acute phonotrauma.

PMID- 16905295
TI  - Association study of IL10, IL1beta, and IL1RN and schizophrenia using tag SNPs
      from a comprehensive database: suggestive association with rs16944 at IL1beta.
AB  - Genetic association studies of several candidate cytokine genes have been
      motivated by evidence of immune dysfunction among patients with schizophrenia.
      Intriguing but inconsistent associations have been reported with polymorphisms of
      three positional candidate genes, namely IL1beta, IL1RN, and IL10. We used
      comprehensive sequencing data from the Seattle SNPs database to select tag SNPs
      that represent all common polymorphisms in the Caucasian population at these
      loci. Associations with 28 tag SNPs were evaluated in 478 cases and 501
      unscreened control individuals, while accounting for population sub-structure
      using the genomic control method. The samples were also stratified by gender,
      diagnostic category, and exposure to infectious agents. Significant association
      was not detected after correcting for multiple comparisons. However, meta
      analysis of our data combined with previously published association studies of
      rs16944 (IL1beta -511) suggests that the C allele confers modest risk for
      schizophrenia among individuals reporting Caucasian ancestry, but not Asians
      (Caucasians, n=819 cases, 1292 controls; p=0.0013, OR=1.24, 95% CI 1.09, 1.41).

PMID- 16905296
TI  - Effect of pulverization and dehydration on the pharmaceutical properties of
      calcium lactate pentahydrate tablets.
AB  - The effects of heat conduction and pulverization on dehydration kinetics and
      tablet hardness were studied by a variety of kinetic equations and physical
      models. The dehydration behavior of unpulverized calcium lactate pentahydrate
      (UCLP) and pulverized calcium lactate pentahydrate (PCLP) tablets was
      investigated by using differential scanning calorimetry (DSC) and powder X-ray
      diffraction (PXRD). The hardness of both UCLP and PCLP tablets was significantly
      decreased after dehydration. The relationship between the extent of dehydration
      and the tablet hardness of both UCLP and PCLP tablets was linear. The results
      suggest that the reduction in tablet hardness is dependent on the dehydration of
      crystal water, and the values of the slopes indicate that the bonding energy of
      the UCLP was stronger than that of the PCLP. The dehydration of both UCLP and
      PCLP tablets at 55 degrees C followed a one-dimensional diffusion mechanism,
      whereas dehydration at storage temperatures of 60-80 degrees C followed a three
      dimensional diffusion mechanism. UCLP and PCLP tablets contracted in thickness
      and diameter during dehydration, but final contraction ratios showed that PCLP
      tablets were more affected than UCLP tablets. In contrast, the micropore radius
      of both UCLP and PCLP tablets increased after dehydration. Thus, the
      pharmaceutical properties of calcium lactate pentahydrate (CLP) tablets are
      affected both by pulverization and by the extent of dehydration of the bulk
      powder in the tablet formulation.

PMID- 16905297
TI  - [IgE-mediated cow's milk allergy].

PMID- 16905299
TI  - Gene expression in fibroadenomas of the rat mammary gland in contrast to
      spontaneous adenocarcinomas and normal mammary gland.
AB  - Fibroadenomas are considered a benign lesion in rodent carcinogenicity studies.
      However, the entity adenocarcinoma arising in fibroadenoma does exist and in
      humans there is evidence of certain forms of fibroadenomas to confer greater risk
      of subsequent breast cancer. In this study, we aim to elucidate the molecular
      features of both spontaneous fibroadenomas and adenocarcinomas. The gene
      expression of the two tumour types is examined and compared to mammary gland in
      the same developmental state and examined for similarities which might indicate
      common molecular pathways. In the present study no similarities were discovered.
      We conclude that in the tumours examined here, no progression to adenocarcinoma
      is likely. Further studies are needed, examining a greater number of tumours and
      including cases of adenocarcinoma arising in fibroadenoma.

PMID- 16905298
TI  - Drug adsorption to plastic containers and retention of drugs in cultured cells
      under in vitro conditions.
AB  - Loss of drug content during cell culture transport experiment can lead to
      misinterpretations in permeability analysis. This study analyses drug adsorption
      to various plastic containers and drug retention in cultured cells under in vitro
      conditions. The loss of various drugs to polystyrene tubes and well plates was
      compared to polypropylene and glass tubes both in deionised water and buffer
      solution. In cellular uptake experiments, administered drugs were obtained from
      cultured cells by liquid extraction. Samples were collected at various time
      points and drug concentrations were measured by a new HPLC-MS/MS method. Acidic
      drugs (hydrochlorothiazide, naproxen, probenicid, and indomethacin) showed little
      if any sorption to all tested materials in either water or buffer. In the case of
      basic drugs, substantial loss to polystyrene tubes and well plates was observed.
      After 4.5 h, the relative amount remaining in aqueous test solution stored in
      polystyrene tubes was 64.7 +/- 6.8%, 38.4 +/- 9.1%, 31.9 +/- 6.7%, and 23.5 +/-
      6.1% for metoprolol, medetomidine, propranolol, and midazolam, respectively.
      Interestingly, there was no significant loss of drugs dissolved in buffer to any
      of the tested materials indicating that buffer reduced surficial interaction. The
      effect of drug concentration to sorption was also tested. Results indicated that
      the higher the concentration in the test solution the lower the proportional drug
      loss, suggesting that the polystyrene contained a limited amount of binding
      sites. Cellular uptake studies showed considerable retention of drugs in cultured
      cells. The amounts of absorbed drugs in cellular structures were 0.45%, 4.88%,
      13.15%, 43.80%, 23.57% and 11.22% for atenolol, metoprolol, medetomidine,
      propranolol, midazolam, and diazepam, respectively. Overall, these findings will
      benefit development and validation of further in vitro drug permeation
      experiments.

PMID- 16905300
TI  - Differentiation of spontaneous and induced mammary adenocarcinomas of the rat by
      gene expression profiling.
AB  - The differentiation of spontaneous and induced adenocarcinomas is of interest in
      the setting of carcinogenicity studies. In the experiment reported here, a
      differentiation of morphologically similar spontaneous and induced mammary
      adenocarcinomas of the rat is achieved by gene expression profiling. By choosing
      one marker gene based on the gene expression profile for each tumour type, we
      were able to distinguish the tumours by real-time quantitative polymerase chain
      reaction (RT-QPCR) as well.

PMID- 16905301
TI  - Effect of monensin on the enzymes of oxidative stress, thiamine pyrophosphatase
      and DNA integrity in rat testicular cells in vitro.
AB  - Monensin, a sodium specific ionophore was evaluated for its in vitro effects on
      rat testis by studying changes at biochemical parameters as well as at the DNA
      level. It was observed that monensin produced marked alterations in the
      activities of various enzymes associated with the testicular functions. The
      significant inhibition of different enzymes of oxidative defense system points
      toward the generation of reactive oxygen species (ROS) by monensin treatment. The
      significant depletion of reduced glutathione and elevation in the level of lipid
      peroxidation further support the above findings. The significant inhibition of
      the activities of lactate dehydrogenase and adenosine triphosphatase shows the
      interference of monensin with the normal energy supply in spermatogenesis.
      Moreover, the significant increase in the activities of acid phosphatase and
      thiamine pyrophosphatase demonstrates the interference of monensin with the Golgi
      lysosomal complex of the rat testis. Induced DNA fragmentation indicates towards
      the impact of monensin on the DNA integrity and apoptosis. Further studies are
      needed to understand the important molecular mechanisms responsible for these
      effects.

PMID- 16905302
TI  - Value of host range, morphological, and genetic characteristics within the
      Entomophthora muscae species complex.
AB  - Entomopthora muscae sensu lato is a complex of morphologically similar fungal
      species pathogenic to evolutionarily advanced flies (Cyclorrhapha). To reach an
      operational species definition and recognition of species within this complex,
      the values of host range, morphological and genetic characteristics are
      reconsidered. Within the E. muscae species complex morphological and nuclear
      characteristics of the primary conidia are taxonomically important. In this study
      we compared the dimensions and nuclear numbers of the primary conidia of isolates
      from their original (natural) hosts and after being transferred to alternative
      hosts (cross-transmission) in order to check the stability of these
      characteristics. The conidial characteristics change substantially when produced
      in alternative host species, but their overall range in variability still fit
      within the traditional morphological species circumscriptions. The phylogenetic
      analyses of the ITS II and LSU rRNA gene sequences, revealed three distinct
      lineages within the complex: E. schizophorae, E. muscae and E. syrphi. Within
      each of these lineages sequence divergence was seen between isolates originating
      from different host species. Our studies on the physiological host range showed
      that several isolates were able to infect alternative dipteran species. Musca
      domestica was a particularly good receptor. The ecological host range of any
      individual isolate seems, however, to be limited to one host species evidenced by
      the occurrence of distinct genotypes within each natural infected host species
      shown by RAPD. The high host specificity of these fungi emphasizes the importance
      of identifying the host taxon at species level in the recognition of
      Entomophthora species. We recommend that morphological characteristics of fungal
      structures and host taxon, together with molecular data, serve as criteria for
      species determination in future studies on members of the E. muscae complex.

PMID- 16905303
TI  - Regulation of cell-cell junctions by the cytoskeleton.
AB  - A major form of animal cell-cell adhesion results from the dynamic association of
      cadherin molecules, cytosolic catenins and actin microfilaments. Cadherins
      dynamically regulate the cytoskeleton. In turn, the actin cytoskeleton
      contributes to cadherin molecule oligomerization at cell contacts and to cell
      reshaping in response to environmental changes. Over the past two years, this
      evolutionarily conserved adhesion system has been intensively revisited in both
      its structural and functional aspects; this is illustrated by the remarkable
      progress in the determination of physical parameters of cadherin bonds (including
      force measurement) and the new insights into the role of alpha-catenin and the
      regulation of actin dynamics at cadherin contacts. Other recent studies uncover
      the important contribution of acto-myosin, microtubules and cell tension to
      adherens junction formation, cell differentiation and tissue
      reshaping/remodeling. An open challenge is now to integrate these new data with
      the diversity of cadherin adhesive complexes.

PMID- 16905304
TI  - Electrochemical study of the effect of nano-zinc oxide on microperoxidase and its
      application to more sensitive hydrogen peroxide biosensor preparation.
AB  - Direct electron transfer reactions of microperoxidase were achieved with the help
      of semiconductive zinc oxide nanoparticles on a pyrolytic graphite electrode. The
      enzyme could also exhibit fine electrocatalytic activity towards the reduction of
      hydrogen peroxide. Thereby, a hydrogen peroxide biosensor was constructed based
      on the electrocatalysis of microperoxidase. Further studies revealed that after
      irradiating the microperoxidase/zinc oxide nanoparticles co-modified electrode
      with UV light for 4h, the catalytic ability of microperoxidase could be greatly
      promoted, which could be beneficial to developing more sensitive hydrogen
      peroxide biosensors. As comparison, it was found that the catalytic activity of
      the enzyme would be depressed if microperoxidase/agarose co-modified electrode
      was irradiated. We supposed it was the photovoltaic effect of the zinc oxide
      nanoparticles that improved the catalytic ability of microperoxidase.

PMID- 16905305
TI  - High-sensitivity detection for model organophosphorus and carbamate pesticide
      with quartz crystal microbalance-precipitation sensor.
AB  - The effect of acetylcholinesterase (AChE) immobilization over the surface of a
      quartz crystal microbalance (QCM), by chemisorption of the AChE thiolated with a
      heterobifunctional cross-linker, sulfo-succinimidyl-6-[3-(2
      pyridyldithio)propionamido]hexanoate, and carboxyl-amine coupling of AChE to 3
      mercaptopropionic acid self-assembled monolayer, on the responses of a batch-type
      QCM-precipitation sensor was compared, resulting in a better sensitivity and
      binding efficiency in the former method. When an inhibition study with the
      developed sensor was undertaken at the optimized AChE immobilization with varying
      concentrations of a model organophosphorus pesticide EPN and carbamate one
      carbofuran, a sensitive detection for them was possible with the limit of
      detection corresponding to 1.55 x 10(-8) and 1.30 x 10(-9)M, respectively.

PMID- 16905306
TI  - Remodeling plans for cellular specialization: unique styles for every room.
AB  - Chromatin-remodeling complexes are biochemically diverse, functionally selective
      machines that regulate crucial aspects of DNA metabolism, including transcription
      and chromatin assembly. These complexes modulate histone-DNA interactions to
      affect nucleosome repositioning and disassembly, and histone variant exchange,
      thereby generating compositionally specialized chromatin. Recent studies have
      revealed precise mechanisms by which specific remodelers control the transition
      from proliferating progenitors to committed cells through a highly synchronized
      switch in transcriptional programs. This involves temporal and, often, signal
      dependent gene-targeted interactions between individual remodelers and tissue
      specific master proteins that regulate myogenesis, neurogenesis and
      lymphogenesis. Distinct remodelers have also been shown to direct self-renewal of
      different types of stem cells in response to particular microenvironments.

PMID- 16905307
TI  - Background to Eusoma guidelines and statements.
AB  - The European Society of Mastology (Eusoma) is committed in writing and diffusing
      guidelines on Breast Cancer, aiming at harmonising the quality of Breast Cancer
      care throughout Europe. To achieve this Eusoma organises scientific meetings,
      "workshops" or "Consensus meeting", inviting European experts from the different
      disciplines involved in the multidisciplinary management of Breast Cancer
      patients, to give their contribution in drafting "guidelines" or "consensus
      statements". In this regard Eusoma Executive Committee members found it
      appropriate to define the rules to organise its scientific meetings and to write
      the documents resulting from these meetings, i.e guidelines or statements. This
      will guarantee an homogeneity in the meeting organisations and in drawing up the
      scientific documents.

PMID- 16905308
TI  - Binding of progesterone to cell surfaces of human granulosa-lutein cells.
AB  - Progesterone is produced by granulosa cells under the influence of luteinizing
      hormone. Nuclear progesterone receptors have been found in rat granulosa cells.
      Human granulosa-lutein cells rapidly respond to progesterone with an increase in
      intracellular calcium suggesting the existence of a nongenomic mechanism. This
      study was conducted to determine whether binding of progesterone to granulosa
      cells could occur at the membrane. Granulosa cells were obtained from an in vitro
      fertilization program and examined immunohistochemically with an antiserum to
      membrane progesterone receptors. Approximately 14-70% of freshly harvested or
      cultured granulosa cells of six patients showed a positive reaction to the
      antiserum, limited to the cell membrane. Western blot analysis of homogenates of
      granulosa cells and a granulosa cell tumour confirmed the presence of
      progesterone receptors A, B and C and low amounts of a putative membrane
      receptor. These results demonstrate that the plasma membranes of human granulosa
      cells possess binding components for progesterone which may be involved in its
      nongenomic mechanism of action.

PMID- 16905309
TI  - Expression of apoptotic genes in testicular germ cells and their modulation by
      luteinizing hormone.
AB  - Gonadotropins regulate spermatogenesis by promoting survival and differentiation
      of germ cells. The molecular markers that are modulated by these hormones to
      ensure survival however have not been described in great detail.
      Immunoneutralization of LH in particular leads to apoptotic cell death of the
      spermatocytes and the round spermatids. In the present study, the expression
      pattern and regulation of apoptotic markers after specific immunoneutralization
      of LH in germ cells purified from rats has been investigated at the RNA and
      protein level. Of the several markers tested, Bax, caspases 1 and 2 and Fadd
      exhibit differential expression, with the round spermatids expressing higher
      levels of caspases 1 and 2, and the spermatocytes expressing higher levels of Bax
      and Fadd. The two cell types therefore exhibit differential expression of
      apoptotic markers. The cell types also differ with respect to their response to
      LH antiserum treatment. Fas and Bax both are up-regulated in the round spermatids
      after 24h of antiserum treatment. In the spermatocytes, Fas was up-regulated as
      early as 12h after antiserum treatment while Bax was up-regulated after 2 days.
      These results demonstrate that LH regulates survival of germ cells by modulating
      the levels of pro and anti-apoptotic proteins.

PMID- 16905310
TI  - Small bowel obstruction caused by secondary tumors.
AB  - Small bowel obstruction in an oncology patient is a common and serious medical
      problem which is associated with diagnostic as well as therapeutic dilemmas.
      While the condition is most commonly caused by postoperative adhesions and
      peritoneal carcinomatosis, other causes have been reported [Cormier WJ, Gaffey
      TA, Welch JM, et al. Linitis plastica caused by metastatic lobular carcinoma of
      the breast. Mayo Clinical Proceedings 1980;55:747-53; Clavien P-A, Laffer U,
      Torhos J, et al. Gastrointestinal metastases as first clinical manifestation of
      the dissemination of a breast cancer. European Journal of Surgical Oncology
      1990;16:121-6; Bender GN, Maglinte DD, McLarney JH, et al. Malignant melanoma:
      patterns of metastasis to the small bowel, reliability of imaging studies, and
      clinical relevance. American Journal of Gastroenterology 2001;96:2392-400;
      Gatsoulis N, Roukounakis N, Kafetzis I, et al. Small bowel intussusception due to
      metastatic malignant melanoma. A case report. Technical Coloproctology 2004;8:141
      3; Hung GY, Chiou T, Hsieh YL, et al. Intestinal metastasis causing
      intussusception in a patient treated for osteosarcoma with history of multiple
      metastases: a case report. Japanese Journal of Clinical Oncology 2001;31(4):165
      7; Chen TF, Eardley I, Doyle PT, Bullock KN. Rectal obstruction secondary to
      carcinoma of the prostate treated by transanal resection of the prostate. British
      Journal of Urology 1992;70(6):643-7; Kamal HS, Farah RE, Hamzi HA, et al. Unusual
      presentation of rectal adenocarcinoma. Roman Journal of Gastroenterology
      2003;12(1):47-50; Hofflander R, Beckes D, Kapre S, et al. A case of jejunal
      intussusception with gastrointestinal bleeding caused by metastatic testicular
      germ cell cancer. Digestive Surgery 1999;16(5):439-40]. One of these, reported
      thus far in only very few patients, is obstruction caused by secondary tumors,
      i.e. metastases from other organs to the small bowel wall. As cancer patients
      live longer with improved therapy, physicians are more likely to cope with rare
      phenomena of neoplasms, such as small bowel obstruction caused by secondary
      tumors. We hereby present a review of the relevant medical literature. The goal
      of this article is to define current knowledge on this phenomenon, with emphasis
      on its epidemiology and clinical characteristics, and to increase the awareness
      of the clinician treating cancer patients of such possibility.

PMID- 16905311
TI  - Potential mineralization of nitrogen from organic wastes to ryegrass and wheat
      crops.
AB  - Two-pot experiments with ryegrass and wheat plants were conducted in a Cambic
      Arenosol to test the reliability of N fate predicted by incubation experiments
      previously performed, with the same soil, to assess potentially mineralizable
      nitrogen from six organic wastes (municipal solid waste compost, secondary pulp
      mill sludge, horn meal, poultry manure, solid phase from pig slurry and composted
      pig manure). Two treatments, corresponding to 80 and 160 kgN/ha were tested, with
      or without mineral N fertilization. Experimental data obtained in the pot trials
      was consistent with nitrogen net mineralization trend observed in the aerobic
      incubations with all the wastes tested. Values of potentially mineralizable
      nitrogen (N(0)) from the equations obtained by model fitting, to the incubation
      data, were well correlated to ryegrass and wheat N uptake. Poultry manure was the
      most efficient N supplier to crops.

PMID- 16905312
TI  - Microbial biomass and activity of an agricultural soil amended with the solid
      phase of pig slurries.
AB  - Information about the mineralisation rates and effects on soil microorganisms
      must be obtained prior to the rational use of organic wastes in agriculture or
      forestry. The objective of this work was to study the mineralisation of two
      manures derived from the solid phase of pig slurries and the effects on the soil
      microbial biomass of an agricultural soil. Samples of this soil were mixed at two
      different rates with two manures derived from the solid phase of pig slurry
      (composted, CSP, and non-composted, NSP), and then were incubated during 163
      days. Carbon mineralised from manures was fitted to first-order kinetic model,
      and small differences were found between manures despite the composting of one of
      them. Approximately 45% of the C added was mineralised in the experimental
      period. The soil microbial biomass C (C(mic)) was increased by the amendments
      according to the application rate. The sudden increases of the qCO(2) in the
      treated samples were ephemeral. The most appreciable differences between these
      manures were those related with net N mineralisation, being greater in the NSP
      treated samples. The application of the solid phase of pig slurries, composted or
      not, could be a feasible practice to enhance in a short-term the microbial
      biomass of agricultural soils. In order to avoid an excessive release of
      inorganic N, the use of composted materials is preferred.

PMID- 16905313
TI  - Zeolite (clinoptilolite) as feed additive to reduce manure mineral content.
AB  - Clinoptilolite (a species of zeolite) as grower hog feed additive can potentially
      improve nutrient ingestion and lower manure nutrient levels. A first objective
      was to establish the optimal particle size of the zeolite powder, as a fine size
      increases the adsorption surface while a coarse size can facilitate handling. The
      second objective tested the effect of feeding zeolite on manure nutrient levels.
      For the first objective, three zeolite powders (250-500 microm; 50-250 microm,
      and 50-500 microm) were exposed to an NH(4)(+) solution under a pH of either 7.0
      or 2.0. The resulting solutions were tested for cation exchange. A commercial
      zeolite was also tested for the pH of 2.0 to evaluate zeolite stability. At 0%,
      5% and 10% humidity, the same three particle size powders were subjected to shear
      tests to determine the zeolite's angle of friction. For the second objective
      using metabolic cages, female hogs were subjected to one of four rations (a
      control and three with zeolite) while collecting and analyzing their manures. For
      the first objective, the coarse particle zeolite performed best, adsorbing 158
      and 123 Cmol(+)/kg of NH(4)(+) under neutral and acid pH, respectively, and
      releasing an equivalent amount of minerals only under neutral pH. The commercial
      zeolite with less clinoptilolite released more Al, Fe, Cu and Pb, showing less
      stability. The high internal angle of friction of zeolite did not vary with
      particle size and moisture, indicating funnel flow under gravity. For the second
      objective, hogs fed a zeolite diet produced manure with 15% and 22% less N and P,
      respectively, and demonstrated a better feed conversion, although not
      statistically significant (P>0.05). These results show that there is some
      potential in using high quality clinoptilolite in the ration of grower hogs.

PMID- 16905314
TI  - Study of biochemical and microbiological parameters during composting of pine and
      eucalyptus bark.
AB  - To study the possibility of some residues from pulp and paper industry being used
      as substrates to produce seedlings in containers, three composting experiments
      were carried out using eucalyptus bark, pine bark and a mixture (60:40, v:v) of
      pine bark+eucalyptus bark. Biochemical parameters studied were: acid and alkaline
      phosphatases, lipase (C10), protease, urease, beta-glucosidase and total
      cellulases. The microbiological populations of total aerobic bacteria, total
      fungi, actinomycetes, nitrifying bacteria, cellulolytic bacteria and fungi were
      also evaluated. At the end of the process physicochemical characterization of
      composts was also performed. Results showed in general that the highest
      microbiological populations as well as for enzymatic activities occurred during
      the thermophilic phase (>40 degrees C) of the process. On the other hand and
      according to the physicochemical characteristics of composts pine bark is the
      most appropriate material to be used in the formulation of substrates to produce
      plants in containers.

PMID- 16905315
TI  - Cytostatic and antiviral 6-arylpurine ribonucleosides. Part 7: synthesis and
      evaluation of 6-substituted purine l-ribonucleosides.
AB  - A series of purine l-ribonucleosides 2a-2i bearing diverse C-substituents (alkyl,
      aryl, hetaryl or hydroxymethyl) in the position 6 were prepared by Pd-catalyzed
      cross-coupling reactions of 6-chloro-9-(2,3,5-tri-O-acetyl-beta-l
      ribofuranosyl)purine with the corresponding organometallics followed by
      deprotection. Unlike their d-ribonucleoside enantiomers that possess strong
      cytostatic and anti-HCV activity, the l-ribonucleosides were inactive except for
      6-benzylpurine nucleoside 2h showing moderate anti-HCV effect in replicon assay.
      A triphosphate of 2h did not inhibit HCV RNA polymerase.

PMID- 16905316
TI  - Des-keto lobeline analogs with increased potency and selectivity at dopamine and
      serotonin transporters.
AB  - A series of des-keto lobeline analogs has been synthesized and evaluated for
      their ability to inhibit the dopamine transporter (DAT) and serotonin transporter
      (SERT) function and for their affinity for the synaptic vesicle monoamine
      transporter (VMAT2), as well as for alpha4beta2( *) and alpha7( *) neuronal
      nicotinic acetylcholine receptors (nAChRs). The enantiomers 8R-hydroxylobel-9-ene
      (3a) and 10S-hydroxylobel-7-ene (3c) exhibited high potency and selectivity at
      SERT and DAT, respectively.

PMID- 16905317
TI  - Synthesis and cytotoxicities of dioscin derivatives with decorated chacotriosyl
      residues.
AB  - Two series of dioscin derivatives (4a-o and 5a-o) with selected modifications at
      the 6' and 4''' positions of the chacotriosyl residue, respectively, were
      synthesized. All the 6'-N-acyl-dioscin derivatives did not show considerable
      inhibitory activities at 10 microM, while most of the 4'''-O-(2-N-acyl)ethyl
      dioscin derivatives behaved as potent as dioscin, against the growth of tumor
      cells.

PMID- 16905318
TI  - Design, synthesis, and antifungal activities in vitro of novel
      tetrahydroisoquinoline compounds based on the structure of lanosterol 14alpha
      demethylase (CYP51) of fungi.
AB  - Novel tetrahydroisoquinoline compounds were designed by coupling structure-based
      de novo design based on the structure of lanosterol 14alpha-demethylase (CYP51).
      The chemical synthesis and the antifungal activities in vitro of them were
      reported. The results exhibited that all of the lead compounds showed potent
      antifungal activities, in which compounds 6 and 7 had equal or stronger
      antifungal activities against five test fungi than that of fluconazole. The
      studies presented here provided the antifungal lead compounds. The affinity of
      the lead molecules for CYP51 was mainly attributed to their non-bonding
      interaction with the apoprotein, which was different from the azole antifungal
      agents.

PMID- 16905319
TI  - Farnesoid X-activated receptor antagonists from a marine sponge Spongia sp.
AB  - Three novel (1-3) and two known (4-5) scalarane sesterterpenes were isolated from
      a marine sponge of the genus Spongia. The isolated compounds showed potent
      inhibition of transactivation for the nuclear hormone receptor, FXR (farnesoid X
      activated receptor), which is a promising drug target to treat
      hypercholesterolemia in humans.

PMID- 16905320
TI  - Effect of augmented plantarflexion power on preferred walking speed and economy
      in young and older adults.
AB  - With age, loss of skeletal muscle mass (sarcopenia) results in decreased muscle
      strength and power. Decreased strength and power, in turn, are closely linked
      with declines in physical function. Preferred walking speed, a marker of physical
      function, is slower in older adults compared to young adults. Research suggests
      that older adults may walk slower as a consequence of decreased plantarflexor
      power at push-off. In this study, we hypothesized that providing additional
      plantarflexion (PF) power during push-off would (1) increase preferred walking
      speed, and (2) reduce metabolic cost of transport (MCOT), in young and older
      adults. PF power was augmented using powered ankle-foot orthoses (PAFOs). The
      PAFOs, which use pneumatic actuators to provide an additional PF moment, were
      based on a design by Ferris et al. [Ferris DP, Czerniecki JM, Hannaford B. An
      ankle-foot orthosis powered by artificial pneumatic muscles. J Appl Biomech
      2005;21:189-97.]. Nine young (23.3+/-1.6 years) and seven older (74.6+/-6.6
      years) adults participated. For the young adults, eight out of nine increased
      their preferred walking speed when push-off power was augmented (1.18+/-0.16 to
      1.25+/-0.16m/s, p=0.03). A similar, but non-significant, trend in preferred
      walking speed was observed for the older adults. With augmented push-off power,
      MCOT for young adults decreased from 0.395+/-0.057 to 0.343+/-0.047 (p=0.008);
      indicating that the neuromuscular system was able to adapt to use external energy
      to reduce metabolic cost. Only three older adults were tested but MCOT values
      showed a similar trend. Augmenting PF power increases gait speed and reduces MCOT
      in young adults. Older adults may need a longer period to take advantage of
      additional push-off power.

PMID- 16905321
TI  - A new model for the determination of limb segment mass in children.
AB  - BACKGROUND: The knowledge of limb segment masses is critical for the calculation
      of joint torques. Several methods for segment mass estimation have been described
      in the literature. They are either inaccurate or not applicable to the limb
      segments of children. Therefore, we developed a new cylinder brick model (CBM) to
      estimate segment mass in children. METHODS: The aim of this study was to compare
      CBM and a model based on a polynomial regression equation (PRE) to volume
      measurement obtained by the water displacement method (WDM). We examined
      forearms, hands, lower legs, and feet of 121 children using CBM, PRE, and WDM.
      The differences between CBM and WDM or PRE and WDM were calculated and compared
      using a Bland-Altman plot of differences. FINDINGS: Absolute limb segment mass
      measured by WDM ranged from 0.16+/-0.04 kg for hands in girls 5-6 years old, up
      to 2.72+/-1.03 kg for legs in girls 11-12 years old. The differences of
      normalised segment masses ranged from 0.0002+/-0.0021 to 0.0011+/-0.0036 for CBM
      WDM and from 0.0023+/-0.0041 to 0.0127+/-0.036 for PRE-WDM (values are mean+/-2
      S.D.). The CBM showed better agreement with WDM than PRE for all limb segments in
      girls and boys. INTERPRETATION: CBM is accurate and superior to PRE for the
      estimation of individual limb segment mass of children. Therefore, CBM is a
      practical and useful tool for the analysis of kinetic parameters and the
      calculation of resulting forces to assess joint functionality in children.

PMID- 16905322
TI  - A kinematic and kinetic comparison of overground and treadmill walking in healthy
      subjects.
AB  - INTRODUCTION: Gait evaluation protocols using instrumented treadmills will be
      increasingly used in the near future. For this reason, it must be shown that
      using instrumented treadmills will produce measures of the ground reaction force
      adequate for inverse dynamic analysis, and differences between treadmill and
      overground gait must be well characterized. METHODS: Overground walking kinetics
      were estimated with the subjects walking at their self-selected comfortable
      walking speed. For the treadmill gait trials, the subjects walked on two
      treadmills, such that heel-strike occurred on the forward treadmill and toe-off
      occurred on the trailing treadmill. The treadmill was set to the average
      overground walking speed. Overground and treadmill data were evaluated using
      Vicon Plug-in Gait. The differences between the maxima and minima of kinematic
      and kinetic parameters for overground and treadmill gait were evaluated. RESULTS:
      The kinematics of treadmill and overground gait were very similar. Twelve of 22
      kinematic parameter maxima were statistically significantly different (p<0.05),
      but the magnitude of the difference was generally less than 2 degrees . All GRF
      maxima were found to be statistically significantly smaller for treadmill versus
      overground gait (p<0.05) as were 15 of 18 moment, and 3 of 6 power maxima.
      However, the magnitude of the differences was comparable to the variability in
      normal gait parameters. The sagittal plane ankle moments were not statistically
      different for treadmill and overground gait. DISCUSSION: We have shown that
      treadmill gait is qualitatively and quantitatively similar to overground gait.
      Differences in kinematic and kinetic parameters can be detected in matched
      comparisons, particularly in the case of kinetic parameters. However, the
      magnitudes of these differences are all within the range of repeatability of
      measured kinematic parameters. Thus, the mechanics of treadmill and overground
      gait are very similar. CLINICAL SIGNIFICANCE: Having demonstrated the essential
      equivalence of treadmill and overground gait, it is now possible for clinical
      movement analysis to take advantage of treadmill-based protocols.

PMID- 16905323
TI  - Synthesis of dopamine transporter selective 3-diarylmethoxymethyl-8-arylalkyl-8
      azabicyclo[3.2.1]octane derivatives.
AB  - A series of diarylmethoxymethyltropane-GBR hybrid analogues with all three
      possible stereochemical orientations at C3 were synthesized and evaluated at
      dopamine and serotonin transporters. The 3alpha derivatives were found to be the
      most potent compounds with the 3alpha-di(4-fluorophenyl)methoxymethyl-8-(3
      phenylpropyl)-8-azabicyclo[3.2.1]octane 15b (Ki = 5 nM) being the most potent
      compound of the series. The corresponding 3-di(4-fluorophenyl)-methoxymethyl-8-(3
      phenylpropyl)-8-azabicyclo[3.2.1]oct-2-ene 12b (Ki = 12 nM) was slightly less
      potent than the 3alpha-analogue, while the 3beta-di(4-fluorophenyl)methoxymethyl
      8-(3-phenylpropyl)-8-azabicyclo[3.2.1]octane 23b (Ki = 78 nM) exhibited only
      modest affinity for the dopamine transporter. Only the 3alpha-analogue 15b
      (SERT/DAT = 48) exhibited higher SERT/DAT selectivity than GBR 12909. These
      results indicate that the dopamine transporter can tolerate some variability in
      proximity of the benzhydryl ether to the basic nitrogen atom of the tropane
      without loss in potency. In addition, the structure-activity data for these
      tropane-GBR 12909 hybrid analogues support previous findings that the
      stereochemical and conformational effects imparted by unsaturation at C3 are
      important for dopamine transporter selectivity over the serotonin transporter.

PMID- 16905324
TI  - Natural radiation doses for cosmic and terrestrial components in Costa Rica.
AB  - A study of external natural radiation, cosmic and terrestrial components, was
      carried out with in situ measurements using NaI scintillation counters while
      driving along the roads in Costa Rica for the period July 2003-July 2005. The
      geographical distribution of the terrestrial air-absorbed dose rates and the
      total effective dose rates (including cosmic) are represented on contour maps.
      Information on the population density of the country permitted the calculation of
      the per capita doses. The average effective dose for the total cosmic component
      was 46.88+/-18.06 nSvh(-1) and the average air-absorbed dose for the terrestrial
      component was 29.52+/-14.46 nGyh(-1). The average total effective dose rate
      (cosmic plus terrestrial components) was 0.60+/-0.18 mSv per year. The effective
      dose rate per capita was found to be 83.97 nSvh(-1) which gives an annual dose of
      0.74 mSv. Assuming the world average for the internal radiation component, the
      natural radiation dose for Costa Rica will be 2.29 mSv annually.

PMID- 16905325
TI  - No evidence of association between BDNF gene variants and age-at-onset of
      Huntington's disease.
AB  - Huntington's disease (HD) is a late-onset, autosomal dominant neurodegenerative
      disease caused by a CAG trinucleotide expansion. The number of repeats on the HD
      chromosome explains most of the variability in age of onset, but genetic factors
      other than the HD gene are responsible for part of the residual variance. Based
      on the role played by the brain derived neurotrophic factor (BDNF) in
      neurodysfunction and neurodegeneration in HD, we searched for novel polymorphisms
      in the neuron restrictive silencer element located in the BDNF promoter. Then,
      the effect of the Val66Met variant in determining age of onset was tested in a
      large sample of HD carriers by using a multivariate regression approach. The CAG
      repeat number accounted for 62% of the variance. After correction for the
      predominant effect of the CAG expansion, no multiple regression model provided
      evidence of association between the Val66Met genotype and variation in age-at
      onset. Additional studies are warranted to further investigate BDNF as genetic
      modifier of the HD phenotype.

PMID- 16905327
TI  - Phototoxicity of a core-modified porphyrin and induction of apoptosis.
AB  - A core-modified porphyrin, 5-phenyl-10,15-bis(carboxylatomethoxyphenyl)-20-(2
      thienyl)-21,23-dithiaporphyrin (IY69) was studied in vitro for photodynamic
      activity under a variety of experimental protocols. Variables included the cell
      line (the rodent mammary tumor cell line R3230AC or the human breast cancer cell
      line MCF-7), light fluence, time of exposure of the cell cultures to IY69, and
      the time post-irradiation for cell counting. The length of time cell cultures
      were exposed to IY69 impacted cellular accumulation and cellular localization,
      phototoxicity, and the apparent mode of cell death - apoptosis vs. necrosis.

PMID- 16905326
TI  - Photochemical and phototoxic activity of berberine on murine fibroblast NIH-3T3
      and Ehrlich ascites carcinoma cells.
AB  - The present study demonstrates photoinduced generation of superoxide anion
      radical and singlet oxygen upon UVA irradiation of berberine chloride, and its
      cytotoxic/phototoxic effects on murine fibroblast non-cancer NIH-3T3 and Ehrlich
      ascites carcinoma (EAC) cells. The EPR spectra monitored upon photoexcitation of
      aerated solutions of berberine evidenced the efficient activation of molecular
      oxygen via Type I and II mechanisms, as the generation of superoxide anion
      radical and singlet oxygen was observed. The EAC cell line was more sensitive to
      the effect of non-photoactivated and photoactivated berberine than the NIH-3T3
      cell line. UVA irradiation increased the sensitivity of EAC cells to berberine,
      while the sensitivity of NIH-3T3 cells to photoactivated berberine was not
      changed. Berberine significantly induced direct DNA strand breaks in tested
      cells, oxidative lesions were not detected, and the effect of irradiation of
      cells after berberine treatment did not affect the increase of DNA damage in EAC
      and NIH-3T3 cells. The DNA damage generated by a combination of berberine with
      UVA irradiation induced a significant blockage of EAC cells in the S and G(2)/M
      phases and the stopping/decrease of cell proliferation after 24h of influence. On
      the other hand, after 36h or 48h of berberine treatment, the DNA damage induced
      necrotic or apoptotic death of EAC cells. Whether these divergences are caused by
      differences in the properties of two non-isogenic cell lines or by different
      berberine uptake and cell localization will be analyzed in our further
      investigations.

PMID- 16905328
TI  - Reversed-phase liquid chromatography in-line with negative ionization
      electrospray mass spectrometry for the characterization of the disulfide-linkages
      of an immunoglobulin gamma antibody.
AB  - In this report, we present a new approach for the determination of the disulfide
      bond connectivity in proteins using negative ionization mass spectrometry of
      nonreduced enzymatic digests. The mass spectrometric analysis in negative ion
      mode was optimized to allow in-line analysis coupled directly to the HPLC system
      used for the separation of the peptides resulting from enzymatic digestion. We
      determined the disulfide structure of a human immunoglobulin gamma 2 (IgG2)
      antibody containing 18 unique cysteine residues linked via 11 unique disulfide
      bonds. The efficiency of the gas-phase dissociation of disulfide-linked peptides
      using negative electrospray ionization was evaluated for an ion trap mass
      spectrometer and an orthogonal acceleration time-of-flight mass spectrometer.
      Both mass spectrometry techniques provided efficient in-source fragmentation for
      the identification of the disulfide-linked peptides of the antibody. Both
      instruments were limited in the number of disulfide bonds that could be
      dissociated. Seven of the 11 unique disulfide linkages have been determined,
      including the linkage of the light chain to the heavy chain. Only the disulfide
      connectivity of the hinge peptide H6H7H8H9 (C6C7VEC8PPC9PAPPVAGPSVFLFPPKPK) could
      not be determined (numbering the cysteine residues sequentially from the N
      terminus and labeling the heavy chain cysteines "H" and the light chain cysteines
      "L"). However, we identified the dimer of peptide C6C7VEC8PPC9PAPPVAGPSVFLFPPKPK
      linked via four disulfide bonds based on the unique molecular weight of this
      dipeptide. The established linkages were H1 to H2, H10 to H11, H12 to H13, L1 to
      L2, L3 to L4, and L5 to H3H4. The intrachain linkages of the light chain (L1 to
      L2, L3 to L4), and heavy chain (H10 to H11, H12 to H13) domains were identical to
      the linkages found in IgG1 antibodies.

PMID- 16905329
TI  - Localization of noncovalent complexes in MALDI-preparations by CLSM.
AB  - The unambiguous detection of noncovalent complexes (NCCs) by matrix-assisted
      laser desorption/ionization mass spectrometry (MALDI-MS) is still a far cry from
      being routine. For protein NCCs such as their quaternary structure it has been
      reported that signals of the intact complex are only obtained for the first or at
      most the first few laser exposures of a given sample area. This observation was
      called the first-shot phenomenon. In the present study, this first-shot
      phenomenon has been investigated for the hexameric protein complex
      allophycocyanine (APC) by two independent methods, MALDI-MS with a (nearly) pH
      neutral matrix 6-aza-2-thiothymine (6-ATT) and by imaging the fluorescence of the
      complex in APC-6-ATT preparations by confocal laser scan microscopy (CLSM). The
      intact APC heterohexamer loses its visible fluorescence upon dissociation into
      its subunits. Both methods consistently show that intact APC complexes are
      precipitated at the matrix crystal surface, but dissociate upon incorporation
      into the matrix crystals.

PMID- 16905330
TI  - Monitoring enzyme reaction and screening enzyme inhibitor based on MALDI-TOF-MS
      platform with a matrix of oxidized carbon nanotubes.
AB  - A matrix assisted laser desorption/ionization time-of-flight mass spectrometry
      platform for quantitatively monitoring enzyme activity and screening enzyme
      inhibitors has been demonstrated. The described method employs a new matrix of
      oxidized carbon nanotubes. Compared with the traditional fluorescence approach,
      this label-free method has the advantage of directly identifying the substrates
      and products in enzymatic reactions. Moreover, the method could be conveniently
      carried out with any commercial mass spectrometer without modification. We
      quantitatively monitored the acetylcholinesterase activity and screened
      acetylcholinesterase inhibitors with a detection rate of about 3.3 s per sample.

PMID- 16905331
TI  - Travelling with the BAFF/BLyS family: are we there yet?

PMID- 16905333
TI  - Residual DNA in thermostable DNA polymerases - a cause of irritation in
      diagnostic PCR and microarray assays.
AB  - In a validation trial of a DNA microarray test for chlamydiae we repeatedly
      observed false-positive PCR amplicons from truly negative samples and non
      template controls. Various PCR tests, microarray hybridization and DNA
      sequencing, revealed that residual Escherichia coli DNA from thermostable DNA
      polymerases was the cause of this cross-reaction. A subsequent survey showed that
      only five out of 23 commercial polymerases were free of E. coli DNA. When
      designing generic oligonucleotide sequences for PCR and PCR microarray-based
      assays one should be aware of such possible internal contamination, particularly
      when the target organism is E. coli.

PMID- 16905334
TI  - Evaluation of voxel-based methods for the statistical analysis of PIB PET amyloid
      imaging studies in Alzheimer's disease.
AB  - Deposition of amyloid plaques is believed to be a central event in the
      development of Alzheimer's disease (AD). The present study was undertaken to
      evaluate statistical methods for the assessment of group differences in retention
      of an amyloid imaging agent, PIB, throughout the brain and to compare these
      results to FDG studies of glucose metabolism performed in the same subjects on
      the same day. PET studies were performed in 10 mild to moderate AD and 11 control
      subjects. Parametric images of PIB retention (over 90 min post-injection) were
      generated using the Logan graphical analysis with cerebellar (CER, reference
      region) data as input. FDG parametric images were created by summing the uptake
      over 40-60 min post-injection and normalizing that to the CER to give a
      standardized uptake value ratio. Data were compared using parametric (SPM) and
      non-parametric (SnPM) statistical methods with familywise error (FWE) and false
      discovery rate (FDR) corrections. PIB results were consistent with previous
      regional results as AD subjects showed highly significant retention in frontal,
      parietal, temporal, and posterior cingulate cortices (FDR-corrected p<1.4e-10).
      FDG results showed regions of marginally significant decreases in uptake in AD
      subjects (frontal, parietal, temporal, posterior cingulate cortices: FDR
      corrected p<0.1) consistent with previous studies. Relative to FDG, the PIB
      analyses were of greater statistical significance and larger spatial extent.
      Additionally, the PIB analyses retained significance after both FWE and FDR
      corrections. These results indicate that voxel-based methods will be useful for
      future larger longitudinal studies of amyloid deposition that could improve AD
      diagnosis and anti-amyloid therapy assessment.

PMID- 16905335
TI  - White and gray matter development in human fetal, newborn and pediatric brains.
AB  - Brain anatomy is characterized by dramatic growth from the end of the second
      trimester through the neonatal stage. The characterization of normal axonal
      growth of the white matter tracts has not been well-documented to date and could
      provide important clues to understanding the extensive inhomogeneity of white
      matter injuries in cerebral palsy (CP) patients. However, anatomical studies of
      human brain development during this period are surprisingly scarce and histology
      based atlases have become available only recently. Diffusion tensor magnetic
      resonance imaging (DTMRI) can reveal detailed anatomy of white matter. We
      acquired diffusion tensor images (DTI) of postmortem fetal brain samples and in
      vivo neonates and children. Neural structures were annotated in two-dimensional
      (2D) slices, segmented, measured, and reconstructed three-dimensionally (3D). The
      growth status of various white matter tracts was evaluated on cross-sections at
      19-20 gestational weeks, and compared with 0-month-old neonates and 5- to 6-year
      old children. Limbic, commissural, association, and projection white matter
      tracts and gray matter structures were illustrated in 3D and quantitatively
      characterized to assess their dynamic changes. The overall pattern of the time
      courses for the development of different white matter is that limbic fibers
      develop first and association fibers last and commissural and projection fibers
      are forming from anterior to posterior part of the brain. The resultant DTMRI
      based 3D human brain data will be a valuable resource for human brain
      developmental study and will provide reference standards for diagnostic radiology
      of premature newborns.

PMID- 16905336
TI  - Evolution in temperate and tropical seas: disparate patterns in southern
      hemisphere abalone (Mollusca: Vetigastropoda: Haliotidae).

PMID- 16905337
TI  - Circumpolar phylogeography of Juncus biglumis (Juncaceae) inferred from AFLP
      fingerprints, cpDNA sequences, nuclear DNA content and chromosome numbers.
AB  - We explored the circumpolar phylogeographic history of the arctic-alpine Juncus
      biglumis using amplified fragment length polymorphisms (AFLPs), sequences of
      cpDNA, relative nuclear DNA content and chromosome numbers. The analyses of the
      AFLP and cpDNA data gave congruent results and revealed three distinct clades.
      One of them, represented by a single population from the Taymyr peninsula in
      northern Siberia, had approximately fourfold larger genome size than the other
      samples and produced an AFLP pattern that was too aberrant to be analysed
      together with the rest of the data set. The two other clades represented
      different ploidy levels (2n = 60 and 120) as judged from chromosome counts of
      selected populations but differed only in c. 6% relative DNA content. Based on
      the AFLP and partly also on the cpDNA data, each of the two main clades was
      further subdivided into two well-supported subgroups. Three of the subgroups were
      widespread and exhibited largely overlapping distribution patterns. The fourth
      subgroup seems to be absent from the North Atlantic region and from western
      Siberia. We suggest that the four subgroups diverged during isolation in
      different glacial refugia during the Quaternary. Interestingly, individuals of
      both main clades were encountered in geographically close populations in eastern
      Greenland and even within a single population from Svalbard, indicating that both
      areas were colonised at least twice. The different genome sizes and ploidy levels
      strongly suggest that the three main clades represent distinct gene pools and act
      as cryptic species.

PMID- 16905338
TI  - Incongruous nuclear and mitochondrial phylogeographic patterns in two sympatric
      lineages of the wolf spider Pardosa astrigera (Araneae: Lycosidae) from China.
AB  - We investigated the genetic structure of mitochondrial DNA (COI and 16S rRNA
      tRNA(Leu(CUN))-ND1) and nuclear DNA (ITS2) variations among and within
      populations of Pardosa astrigera in China. Two phenotypes of males were
      recognized. They differed genetically also in the presence (type A) or absence
      (type B) of common insertions and deletions in ITS2. The concordance between
      mtDNA based phylogeny and the phenotypic variations of P. astrigera was weak.
      Haplotypes of type A did not form a monophyletic group. Instead they were found
      in three clades, in one of them mixed with type B haplotypes, most likely as a
      result of long-term and ongoing gene flow of mtDNA between the two phenotypic
      groups (M = 0.69). Pairwise sequence divergences of all data sets indicated that
      the genetic divergences between the two phenotypes fall within intraspecific
      range. Our results indicated that the P. astrigera populations in China consist
      of two sympatric lineages with male phenotypic variations. Patterns of mismatch
      distribution within lineages suggested long-term demographic stability in the
      lineage A, and growth in lineage B that expanded rapidly and recolonized from a
      southern refuge to the northern parts of China during the late-Pleistocene. On
      the basis of the estimated divergence time between the two lineages (0.18-0.41
      Ma), we suggest that the dry-cold climate and the uplift of the Tibetan plateau
      during the mid-Pleistocene appear to have a determinating impact on the
      evolutionary history of P. astrigera in China.

PMID- 16905339
TI  - A bladder-cooling reflex in the anaesthetised guinea-pig: a model of the positive
      clinical ice-water test.
AB  - INTRODUCTION: In patients with detrusor hyperreflexia, intravesical instillation
      of ice-cold water results in the development of involuntary bladder contractions
      at volumes less than normal cystometric capacity. This is referred to as a
      positive ice-water test (+IWT) and can be reversed by vanilloid receptor agonists
      and potentiated by menthol. The present study was designed to investigate the
      existence of an analogous cooling reflex in the guinea-pig bladder that could be
      used as a small animal model in order to test the effects of drugs on the reflex.
      METHODS: Bladder pressure and external urethral sphincter electromyogram (EUS
      EMG) were recorded in alpha-chloralose/urethane anaesthetised guinea-pigs during
      rapid infusion of cold or warm saline into the bladder with or without prior
      intravesical exposure to menthol or resiniferatoxin (RTX). RESULTS: The mean
      control micturition threshold volume (TV) of 2.58 ml at 38 degrees C was reduced
      to 1.52 ml in response to saline infusion at 3 degrees C (P=0.001). The cold
      induced reduction in TV was reproducible during several subsequent repeat
      infusions at 38 degrees C and 3 degrees C and was accompanied by decreases in
      bladder voiding pressure. The duration of the micturition reflex was markedly
      increased following cold compared with warm saline infusion (mean 24.5 s at 3
      degrees C, 10.2 s at 38 degrees C, P=0.001) and was associated with oscillations
      in bladder pressure and concomitant bursting activity in the EUS EMG. During step
      wise decreases in infusate temperature from 38 degrees C to 23 degrees C, 15
      degrees C, 7 degrees C and 3 degrees C, the threshold infusate temperature to
      elicit a significant reduction in TV was 15 degrees C. The reduction in TV at 3
      degrees C was potentiated by intravesical infusion of 0.6 mM menthol whilst
      intravesical infusion of 500 nM RTX reversed the reduction in TV at 3 degrees C.
      DISCUSSION: These data suggest that a bladder-cooling reflex is present in the
      anaesthetised guinea-pig and represents a useful small animal model of the
      clinical +IWT.

PMID- 16905340
TI  - Comparison of mechanical debridement and radiofrequency energy for chondroplasty
      in an in vivo equine model of partial thickness cartilage injury.
AB  - OBJECTIVE: The purpose of this study was to develop a long-term model of
      cartilage injury that could be used to compare the effects of radiofrequency
      energy (RFE) and mechanical debridement as a treatment. METHODS: Partial
      thickness fibrillation of patellar cartilage was created in 16 mature ponies.
      Three months after the initial surgery all injured patellae were randomly
      selected to receive one of the four treatments (n = 8/treatment): (1) control,
      (2) mechanical debridement with a motorized shaver, (3) TAC-CII RFE probe, and
      (4) CoVac 50 RFE probe. The ponies were euthanized 22 months after treatment.
      Macroscopic appearance of the cartilage surface was scored, vital cell staining
      was used to determine chondrocyte viability and light microscopy was used to
      grade the morphometric changes within the cartilage. Mechanical properties
      (aggregate modulus, Poisson's ratio and permeability) also were determined and
      compared to normal uninjured cartilage. RESULTS: There were no differences in the
      cartilage surface scores among the treatment groups and control samples (P >
      0.05). The maximum depth of cell death and the percentage of dead area in control
      and mechanical debridement groups were significantly less than those in both RFE
      groups. There were no significant differences in maximum depth and the percentage
      of dead area between the two RFE treatment groups. Histologic scores demonstrated
      better cartilage morphology for the control and mechanical debridement groups
      than those of RFE groups. However, even with full thickness chondrocyte death,
      the matrix in the RFE treated sections was still retained and the mechanical
      properties of the treated cartilage did not differ from the mechanical
      debridement group. CONCLUSION: RFE caused greater chondrocyte death and more
      severe morphological changes compared to untreated degenerative cartilage and
      mechanical debridement in this model.

PMID- 16905341
TI  - Proteoglycan synthesis in bovine articular cartilage explants exposed to
      different low-frequency low-energy pulsed electromagnetic fields.
AB  - OBJECTIVE: To investigate the role of pulsed electromagnetic field (PEMF)
      exposure parameters (exposure length, magnetic field peak amplitude, pulse
      frequency) in the regulation of proteoglycan (PG) synthesis of bovine articular
      cartilage explants. METHODS: Bovine articular cartilage explants were exposed to
      a PEMF (75 Hz; 2 mT) for different time periods: 1, 4, 9, 24 h. Then, cartilage
      explants were exposed for 24 h to PEMFs of different magnetic field peak
      amplitudes (0.5, 1, 1.5, 2 mT) and different frequencies (2, 37, 75, 110 Hz). PG
      synthesis of control and exposed explants was determined by Na2-35SO4
      incorporation. RESULTS: PEMF exposure significantly increased PG synthesis
      ranging from 12% at 4 h to 17% at 24 h of exposure. At all the magnetic field
      peak amplitude values, a significant PG synthesis increase was measured in PEMF
      exposed explants compared to controls, with maximal effect at 1.5 mT. No effect
      of pulse frequency was observed on PG synthesis stimulation. CONCLUSIONS: The
      results of this study show the range of exposure length, PEMF amplitude, pulse
      frequency which can stimulate cartilage PG synthesis, and suggest optimal
      exposure parameters which may be useful for cartilage repair in in vivo
      experiments and clinical application.

PMID- 16905342
TI  - Osteophytes, juxta-articular radiolucencies and cancellous bone changes in the
      proximal tibia of patients with knee osteoarthritis.
AB  - OBJECTIVE: To determine differences in tibial cancellous bone organisation in
      knee osteoarthritis (OA) between the central weight-bearing region and juxta
      articular radiolucencies adjacent to small, medium or large marginal osteophytes.
      METHODS: Patients with medial compartment OA (n = 60; F = 39), mean (SD) age 60.0
      (9.7) years, and non-OA reference subjects (n = 21; F = 5), mean (SD) age 36.8
      (11.5) years, had x4 macroradiographs digitised by laser scanner. Using a
      modified Osteoarthritis Research Society (OARS) Atlas, right and/or left knees
      were graded according to marginal osteophyte size into those with small (n = 30),
      medium (n = 30) or large (n = 27) marginal osteophytes, identified as OPH1, OPH2
      and OPH3, respectively. Non-OA knees (n = 30) were anatomically normal.
      Computerised method of Fractal Signature Analysis (FSA) quantified differences in
      cancellous bone structure between non-OA and osteophyte subgroups at two regions
      of interest (ROIs); central weight-bearing and tibial margin. RESULTS: Compared
      to non-OA, vertical trabecular number increased significantly (P < 0.05) in all
      osteophyte subgroups (width range 0.12-1.14 mm) within both ROIs. In OPH3, this
      increase was significantly (P < 0.05) greater compared to OPH2 in the central
      ROI, and to OPH2 and OPH1 in the marginal ROI at most trabecular widths (0.12
      1.14 mm). In the marginal ROI, compared to non-OA, horizontal trabeculae number
      decreased in all osteophyte subgroups. This decrease was significantly greater in
      OPH3 compared to OPH2 and OPH1 at small to medium trabecular widths (0.12-0.54
      mm). CONCLUSION: Compared to disease associated bone loss at the central ROI of
      the tibia, the extent of juxta-articular bone loss appears to be associated with
      the size of the marginal osteophytes.

PMID- 16905343
TI  - Direct association between caspase 3 and alpha5beta1 integrin and its role during
      anoikis of rat fibroblasts.
AB  - We have demonstrated a direct association between alpha5beta1 integrin and
      caspase 3, both pro- and mature enzyme, in various sub-cellular compartments of
      rat fibroblasts undergoing anoikis. Integrin associated caspase 3 showed high
      activity in the plasma membranes, whereas in the cytosol and microsomal fraction
      it showed little or no activity. Our results suggest a possible role for recycled
      un-ligated alpha5beta1 integrin molecules between cytosol and plasma membrane, in
      regulation of caspase-3 activity and induction of cell death in adhesion-deprived
      cells.

PMID- 16905344
TI  - Cocaine-but not methamphetamine-associated memory requires de novo protein
      synthesis.
AB  - Context-induced drug craving and continuous drug use manifest the critical roles
      of specific memory episodes associated with the drug use experiences. Drug
      induced conditioned place preference (CPP) in C57BL/6J mouse model, in this
      regard, is an appropriate behavioral paradigm to study such drug use-associated
      memories. Requirement of protein synthesis in various forms of long-term memory
      formation and storage has been phylogenetically demonstrated. This study was
      undertaken to study the requirement of protein synthesis in the learning and
      memory aspect of the conditioned place preference induced by cocaine and
      methamphetamine, two abused drugs of choice in local area. Since pCREB has been
      documented as a candidate substrate for mediating the drug-induced
      neuroadaptation, the pCREB level in hippocampus, nucleus accumbens, and
      prefrontal cortex was examined for its potential participation in the formation
      of CPP caused by these psychostimulants. We found that cocaine (2.5 and 5.0
      mg/kg/dose)-induced CPP was abolished by the pretreatment of anisomycin (50
      mg/kg/dose), a protein synthesis inhibitor, whereas methamphetamine (0.5 or 1.0
      mg/kg/dose)-induced CPP was not affected by the anisomycin pretreatment.
      Likewise, cocaine-induced CPP was mitigated by another protein synthesis
      inhibitor, cycloheximide (15 mg/kg/injection) pretreatment, whereas
      methamphetamine-induced CPP remained intact by such pretreatment. Moreover,
      anisomycin treatment 2h after each drug-place pairing disrupted the cocaine
      induced CPP, whereas the same treatment did not affect methamphetamine-induced
      CPP. An increase of accumbal pCREB level was found to associate with the learning
      phase of cocaine, but not with the learning phase of methamphetamine. We further
      found that intraaccumbal CREB antisense oligodeoxynucleotide infusion diminished
      cocaine-induced CPP, whereas did not affect the methamphetamine-induced CPP.
      Taken together, these data suggest that protein synthesis and accumbal CREB
      phosphorylation are essential for the learning and consolidation of the cocaine
      induced CPP, whereas methamphetamine-induced CPP may be unrelated to the
      synthesis of new proteins.

PMID- 16905345
TI  - Perioperative kinetics of the nitric oxide derivatives nitrite/nitrate during
      orthotopic liver transplantation.
AB  - Nitric oxide (NO) is an important mediator in ischemia-reperfusion injury during
      human orthotopic liver transplantation (OLT). The perioperative kinetics of
      nitrite/nitrate plasma levels in 25 patients undergoing uncomplicated OLT were
      studied. A uniform pattern with significant increases of nitrite/nitrate levels
      immediately after reperfusion was seen in all patients, followed by a decrease to
      pretransplant levels within 24h. Peak levels 30 min after reperfusion were
      correlated to the indocyanine green plasma disappearance rate (PDR(ICG)),
      suggesting an association of early released NO with graft perfusion in OLT.

PMID- 16905346
TI  - Visualisation of enantiomers via insertion of a BIRD module in X-H correlation
      experiments in chiral liquid crystal solvent.
AB  - Several 13C-1H NMR techniques are derived simplifying the visualisation of
      enantiomers in chiral ordering solvents. They proceed through various
      heteronuclear 2D experiments where a bilinear rotation decoupling sequence (BIRD)
      is inserted in the middle of the t1 evolution period. In this way, the small
      couplings are refocused while the large couplings are preserved. The methods
      allow extracting precise values of one-bond carbon-proton residual dipolar
      couplings for each enantiomer out of unresolved proton-coupled 13C or carbon
      coupled 1H spectra. Illustrative examples are analysed and discussed using
      various pulse sequences.

PMID- 16905347
TI  - Structural and functional behavior of biologically active monomeric melittin.
AB  - Melittin is a well-known water-soluble toxic peptide present in bee venom of Apis
      mellifera, capable of interacting with and disrupting cell membranes thus
      producing many effects on living cells. Additionally, melittin induces activation
      of phospholipases and calmodulin upon interaction with cellular membranes. The
      conformation and aggregation state adopted by melittin in solution depends on
      several factors including the peptide concentration, ionic strength, pH and the
      nature of the ions in the aqueous medium. Such conformational dependence on the
      peptide environment gives new insights over the currently available 3D structures
      of melittin and, ultimately, over its biologically functional unit. Based on
      crystallographic data, the melittin tetramer has been proposed as its bioactive
      form. Contrarily to such data, we show in this work the results obtained from
      molecular dynamics simulations, which clearly indicate that the tetrameric
      organization of melittin is not stable under biological conditions dissociating
      after 2.5 ns through a 10 ns trajectory. We found that the tetrameric form of
      melittin is stable only in conditions of high pH and high peptide concentration
      in the molecular dynamics simulations. Moreover, when in plasma melittin appears
      to be a random coil monomer, folding only upon interaction with biological
      membranes. In summary, these findings elucidate several properties of melittin
      structure and dynamics, projecting significant implications in the study of its
      biological function.

PMID- 16905348
TI  - Differential effects of anesthetics on electrical properties of the rainbow trout
      (Oncorhynchus mykiss) heart.
AB  - We compared electrocardiographic signals in hatchery-reared, non-spinally
      transected, immature rainbow trout (Oncorhynchus mykiss Walbaum) under clove oil
      (25 ppm), tricaine methanesulfonate (tricaine, 60 ppm), and benzocaine (108 ppm)
      general anesthesia (35 min, 14 degrees C). For all 3 anesthetics, the mean heart
      rate (HR) and QRS amplitude did not differ, and QRS duration and QT interval were
      independent of HR. Heart rate variability (HRV) was significantly (4-fold,
      P=0.032) higher under benzocaine than under clove oil and tricaine, but did not
      differ between clove oil and tricaine. QRS duration differed between groups
      (P<0.001, F=121); benzocaine anesthesia resulted in longer QRS complexes compared
      to clove oil (P<0.001) and tricaine (P<0.001) anesthesia, and QRS complexes under
      clove oil were longer than those under tricaine (P<0.001). High HRV and QRS
      amplitude variation with benzocaine were associated with HR oscillations as
      anesthetic exposure time increased, and suggest benzocaine toxicity which may
      influence cardiac function studies. Similar clove oil and tricaine ECG patterns
      suggest comparable autonomic effects, and maintenance of myocardial excitability.
      Given its low cost, ease of use, and similar ECG profiles to tricaine, clove oil
      is a viable alternative for studies of cardiac function in anesthetized rainbow
      trout.

PMID- 16905350
TI  - Acute respiratory tract infections among Hajj medical mission personnel, Saudi
      Arabia.
AB  - OBJECTIVES: To estimate the prevalence of acute respiratory tract infections
      (ARI) among 250 personnel serving in a Hajj medical mission, Al-Hada and Taif
      Armed Forces Hospitals, during the 2005 season and to determine the effectiveness
      of protective measures, including influenza vaccination, for these infections.
      METHODS: This was a nested case-control study. A questionnaire was distributed to
      the study cohort two weeks after the Hajj period and was self-administered by all
      recruited subjects. In addition, the medical records of study subjects were
      reviewed at Al-Hada Hospital for the same period in order to document ARI.
      RESULTS: The attack rate for ARI among study subjects during Hajj season or
      within two weeks of returning was 25.6% (64/250). Logistic regression analysis of
      factors related to acquiring ARI revealed that contact with pilgrims imposed an
      extremely high risk of infection (adjusted OR 13.2, 95% CI 1.5-117.6). Moreover,
      non-use of alcohol-based hand disinfection carried a more than 8-fold risk of
      acquiring ARI compared to those who always used alcohol for hand disinfection
      (adjusted OR 8.4, 95% CI 2.2-32.2). Smoking was also a predictor of ARI in our
      cohort and influenza vaccination was associated with a 30% reduction in ARI
      compared to unvaccinated subjects, although this finding was not statistically
      significant. Unexpectedly, the logistic regression model showed that Saudi
      nationals were three times more likely to acquire ARI than non-Saudis (adjusted
      OR 3.1, 95% CI 1.2-8.4). CONCLUSIONS: The common practice among pilgrims and
      medical personnel of using surgical facemasks to protect themselves against ARI
      should be discontinued and regular use of alcohol-based hand scrubs should be
      more vigorously encouraged. Further research is needed to evaluate the protective
      value of N95 facemasks against ARI during the Hajj period.

PMID- 16905349
TI  - FABP3 and FABP10 in Atlantic salmon (Salmo salar L.)--general effects of dietary
      fatty acid composition and life cycle variations.
AB  - The increased use of dietary plant oil supplementation combined with high dietary
      lipid loads challenges the lipid transport systems of cultivated fish species.
      Fatty acid binding proteins (FABPs) have been thoroughly studied as intracellular
      fatty acid transporters in vertebrates, but no data have been reported in
      Atlantic salmon. In the present study, comparative characterizations were
      performed, and dietary influence of plant oil supplementation on FABP3 and FABP10
      expression was studied for several tissues in two separate dietary trials. In
      trial I, groups (6 fish each) were fed diets for 42 weeks (body mass 142+/-1 to
      1463+/-83 g) (mean+/-S.D.), containing graded levels of rapeseed oil substituting
      for fish oil using a linear regression design. In trial II, groups (3 fish each)
      were fed 100% fish oil or 100% plant oil for 22 months (0.160+/-0.052 to 2523+/
      590 g) (mean+/-S.D.) and sampled at regular intervals. Liver and muscle tissues
      appeared to express several FABPs possibly linked to different metabolic
      functions. FABPs mRNA expression did not change with dietary inclusion of 75%
      rapeseed oil, whereas FABP3 protein expression seemed to be affected by dietary
      rapeseed oil inclusion. Significant changes in red muscle FABP3 mRNA expression
      correlate to significant changes in total beta-oxidation capacity during the
      energy consuming process of smoltification.

PMID- 16905351
TI  - Matching a transducer to water at cavitation: acoustic horn design principles.
AB  - High-power ultrasound for several decades has been an integral part of many
      industrial processes conducted in aqueous solutions. Maximizing the transfer
      efficiency of the acoustic energy between electromechanical transducers and water
      at cavitation is crucial when designing industrial ultrasonic reactors with large
      active volumes. This can be achieved by matching the acoustic impedances of
      transducers to water at cavitation using appropriately designed ultrasonic horns.
      In the present work, a set of criteria characterizing the matching capabilities
      of ultrasonic horns is developed. It is shown that none of the commonly used
      tapered-shape horns can achieve the necessary conditions. An analytical method
      for designing five-element acoustic horns with the desirable matching properties
      is introduced, and five novel types of such horns, most suitable for practical
      applications, are proposed. An evaluation of the horns' performance is presented
      in a set of experiments, demonstrating the validity of the developed theoretical
      methodology. Power transfer efficiency increase by almost an order of magnitude
      is shown to be possible with the presented horn designs, as compared to those
      traditionally utilized.

PMID- 16905352
TI  - Sonophotocatalytic oxidation of elemental sulphur on titanium dioxide.
AB  - The effect of ultrasound on the photocatalytic oxidation kinetics of elemental
      sulphur particles catalyzed by titanium dioxide was studied using a conductivity
      method to follow the reaction. The simultaneous use of photocatalyst and
      ultrasound have a positive effect on the reaction. The zero-order oxidation rate
      constant of sulphur, reached after an activation period of approximately 150 min,
      was about 20 times higher when the reactor was sonicated, using an ultrasonic
      processor of 30 kHz, compared to the rate found in its absence. Finally, when the
      amount of sulphur is changed in the reactor, saturation kinetics seems to be the
      most appropriate model to describe the oxidation process in the presence of
      ultrasound and, in the other hand, when titanium dioxide was increased, a maximum
      rate was achieved when 0.56 g/L TiO2 were used.

PMID- 16905353
TI  - Wnt4 action in gonadal development and sex determination.
AB  - Wnt4 is a growth factor involved in multiple developmental processes such as the
      formation of the kidney, adrenal, mammary gland, pituitary and the female
      reproductive system. During mammalian embryogenesis, Wnt4 is expressed in the
      gonads of both sexes before sex determination events take place and is
      subsequently down-regulated in the male gonad. Inactivation of the Wnt4 gene in
      mice has revealed that it is involved at several steps of female reproductive
      development. Wnt4 is implicated in Mullerian duct regression, the formation of
      sex-specific vasculature, the inhibition of steroidogenesis and in sex-specific
      cell migration events. A mouse model of sex-reversal has partially unravelled the
      molecular pathways in which Wnt4 operates during the development of the female
      reproductive system. However, the specific molecular mechanism of action of Wnt4
      during gonadal development remains unknown. This and downstream signaling
      pathways involved in Wnt4 action during female gonad development are reviewed and
      models of Wnt4 action are proposed for Mullerian duct formation, sex-specific
      vasculature development, and sex determination events. Further identification of
      critical downstream effectors of the Wnt4 signaling pathway in mouse models and
      in patients with sex-reversal conditions could help in understanding sex-reversal
      pathologies in humans.

PMID- 16905354
TI  - Engineering of glycosidases and glycosyltransferases.
AB  - In recent years, substantial advances have been made in the engineering of
      glycosidases and glycosyltransferases for the synthesis and degradation of glycan
      structures. Key developments include improvement of the thermostability of
      xylanase through comprehensive saturation mutagenesis, creation of the first
      glycosynthase derived from an inverting glycosidase and the emergence of a new
      class of modified glycosidases capable of efficiently synthesizing thioglycosidic
      linkages. Of particular note is the increased use of random mutagenesis and
      directed evolution tactics for tailoring glycosidase activity. Although the
      engineering of glycosyltransferases is still in its early stages, recent work on
      the structure-based alteration of substrate specificity and the manipulation of
      glycosyltransferase profiles in whole cells to effect complex changes in in vivo
      glycobiology probably foreshadows a wave of considerable innovation in this area.

PMID- 16905355
TI  - A novel varicella-zoster virus gE mutation discovered in two Swedish isolates.
AB  - BACKGROUND: Two VZV glycoprotein E (gE D150N) mutant strains were collected in
      North America in 1995 and in 1999. We now report a novel VZV gE mutant virus
      discovered in Europe in two VZV strains collected in Stockholm, Sweden, in 1990
      and 1999. OBJECTIVES: To characterize the two isolates identified among a total
      of 634 VZV isolates collected over a 15-year period at the Karolinska University
      Hospital. STUDY DESIGN: VZV genes were amplified by polymerase chain reaction and
      their sequences were compared to the genomic sequence of VZV-Dumas prototype
      strain. RESULTS: A mutation within the gE gene in an epitope recognized by the
      3B3 monoclonal antibody was identified in both isolates. A different residue was
      changed (R152S) compared to the North American strains (D150N). CONCLUSIONS: The
      occurrence of a VZV gE mutant virus is unusual, but probably a recurring event in
      Europe and North America. It is unknown whether widespread varicella vaccination
      programs will alter the rate at which these mutant viruses are isolated.

PMID- 16905356
TI  - Genotyping of different varicella vaccine strains.
AB  - BACKGROUND: Little is known about single nucleotide polymorphism (SNP) in
      different lots of varicella vaccines distributed by the manufacturers. Recently,
      the genetic analysis of several genomic regions revealed a polymorphism in
      different vaccine lots of Varilrix manufactured by GlaxoSmithKline. These
      findings need attention since mutations in the vaccine strain could result in
      changes of virulence and efficacy of the vaccine. OBJECTIVES: To identify SNPs in
      three varicella vaccine lots of Varilrix and to compare the results with that of
      Varivax as well as the published sequences of the Oka vaccine strain (V-Oka) and
      its parental virus (P-Oka). STUDY DESIGN: The open reading frames (ORF) 1, 6, 10,
      21, 50, 54, and 62 were analyzed by sequencing of amplified DNA fragments.
      RESULTS: Wild-type nucleotides identical to that of P-Oka and/or the European
      wild-type reference strain Dumas and in contrast to V-Oka could be identified in
      ORF 1 of a Varilrix vaccine lot distributed in 1991. In the ORF 62 probably
      responsible for attenuation of V-Oka, this vaccine strain contained 16 SNPs which
      were nearly all wild-type-like. By contrast, different lots of the Varivax
      vaccine revealed uniform sequencing results. The vaccine Varilrix 1999 showed a
      high similarity to the Varivax vaccine currently available. CONCLUSIONS: The
      obvious genetic diversity of different lots of the varicella vaccine Varilrix
      cannot be explained with the coexistence of several strain variants in the
      vaccine, but most likely with different seed lot preparations used for vaccine
      production.

PMID- 16905357
TI  - Merging microfluidics with microarray-based bioassays.
AB  - Microarray technologies provide powerful tools for biomedical researchers and
      medicine, since arrays can be configured to monitor the presence of molecular
      signatures in a highly parallel fashion and can be configured to search either
      for nucleic acids (DNA microarrays) or proteins (antibody-based microarrays) as
      well as different types of cells. Microfluidics on the other hand, provides the
      ability to analyze small volumes (micro-, nano- or even pico-liters) of sample
      and minimize costly reagent consumption as well as automate sample preparation
      and reduce sample processing time. The marriage of microarray technologies with
      the emerging field of microfluidics provides a number of advantages such as,
      reduction in reagent cost, reductions in hybridization assay times, high
      throughput sample processing, and integration and automation capabilities of the
      front-end sample processing steps. However, this potential marriage is also
      fraught with some challenges as well, such as developing low-cost manufacturing
      methods of the fluidic chips, providing good interfaces to the macro-world,
      minimizing non-specific analyte/wall interactions due to the high surface-to
      volume ratio associated with microfluidics, the development of materials that
      accommodate the optical readout phases of the assay and complete integration of
      peripheral components (optical and electrical) to the microfluidic to produce
      autonomous systems appropriate for point-of-care testing. In this review, we
      provide an overview and recent advances on the coupling of DNA, protein and cell
      microarrays to microfluidics and discuss potential improvements required for the
      implementation of these technologies into biomedical and clinical applications.

PMID- 16905358
TI  - Differential regulation of the Chlamydomonas Nar1 gene family by carbon and
      nitrogen.
AB  - Six genes of the Nar1 multigene family from Chlamydomonas reinhardtii were
      identified and are located on chromosomes I, VI, VII, IX, and XII/XIII. The first
      known member Nar1.1 encodes a chloroplast nitrite transporter that regulates
      nitrate assimilation according to carbon availability, and data supporting the
      idea that NAR1 proteins may participate in adjusting both nitrite and carbon
      utilization by Chlamydomonas cells are presented herein. The protein sequences
      deduced from their corresponding cDNAs show the typical signature of the FNT
      family, but also have particular differences: (1) NAR1.1, NAR1.2, and NAR1.5
      contain putative chloroplast transit peptides; and (2) NAR1.3 and NAR1.6 have
      long C-termini. The expression patterns for Nar1 transcripts showed differential
      responses to changes in nitrogen or carbon status, as well as a particular
      regulation by the nitrate assimilation regulatory gene Nit2. One gene, Nar1.2,
      was strongly carbon-regulated independently of Nit2; two genes, Nar1.1 and
      Nar1.6, were regulated by nitrogen and Nit2; and the other genes, Nar1.3, Nar1.4,
      and Nar1.5 were independent of Nit2 and responded to nitrogen or carbon
      treatments in a transient and not easily understandable way. We have used Xenopus
      oocytes as a heterologous system for functional expression of NAR1.2. The
      electrophysiological response to HCO3- and NO2- provides evidence that NAR1.2 is
      involved in both HCO3- and NO2- transport.

PMID- 16905359
TI  - Housekeeping by Leishmania.
AB  - The observation that differentiation of parasite life cycle stages involves
      structural and functional reorganisation is very familiar. A recent paper by
      Besteiro and colleagues provides an intriguing insight into cellular remodelling
      during differentiation. They show that it is essential for Leishmania to tidy up
      and put the house in order before it can differentiate to mammal-infective
      stages.

PMID- 16905361
TI  - Xenotransplantation and ABO incompatible transplantation: the similarities they
      share.
AB  - Transplantation of kidney allografts across the ABO barrier has been feasible
      with the development of technologies for removal of anti-blood group antibodies
      from the circulation of the recipent. The recipients of ABO incompatible grafts
      display tolerance, accommodation or rejection of the graft. Understanding the
      factors that determine the outcome of the immune response against incompatible
      blood group antigens has required the study of an appropriate experimental animal
      model. The model used is that of knockout (KO) mice for the
      alpha1,3galactosyltransferase gene, lacking the alpha-gal epitopes and
      transplanted with wild type mouse heart expressing the alpha-gal epitope. The
      alpha-gal epitope (Galalpha1-3Galbeta1-(3)4GlcNAc-R) is one of the most abundant
      carbohydrate epitopes on cells of non-primate mammals and New World monkeys,
      where it is synthesized by the glycosylation enzyme
      alpha1,3galactosyltransferase. In humans, apes and Old World monkeys, this
      epitope is absent due to an evolutionary event that led to the inactivation of
      the alpha1,3galactosyltransferase gene in ancestral Old World primates. Instead,
      humans, apes and Old World monkeys produce a natural antibody, the anti-Gal
      antibody, that is the most abundant natural antibody in humans (approximately 1%
      of circulating immunoglobulins) and which specifically interacts with alpha-gal
      epitopes. The interaction between anti-Gal and alpha-gal epitopes is a major
      immunologic barrier in xenotransplantation, preventing transplantation of pig
      organs or tissues (i.e. xenografts) into humans. Anti-Gal antibodies also
      comprise a large proportion of anti-blood group B activity in A and O
      individuals. Moreover, in recipients of ABO incompatible grafts, much of the
      elicited anti-A and anti-B antibodies are in fact anti-Gal antibodies capable of
      binding also to the incompatible blood group antigens. Since the alpha-gal
      epitope is very similar in its structure to blood groups A and B, understanding
      anti-Gal response to alpha-gal epitopes is likely to provide information on the
      immune response to ABO incompatible antigens. Studies on the immune response to
      alpha-gal epitopes in KO mice have indicated that this epitope can not activate T
      cells. Anti-Gal B cells engaging alpha-gal epitopes on transplated wild type
      mouse heart can be activated to produce their antibodies only if they receive
      help from T cells that are activated by allogeneic or xenogeneic peptides. If T
      cell help is not available for several days the B cells are induced to
      differentiate into cells capable of producing accommodating antibodies.
      Accommodating anti-Gal antibodies bind to the incompatible carbohydrate antigen
      but do not induce rejection. Prolonged exposure of anti-Gal B cells to the
      incompatible alpha-gal epitope on the wild type mouse heart graft induces
      tolerance due to the deletion of these B cells. These studies imply that similar
      variation in the availability of T cell help in recipients of ABO incompatible
      grafts result in rejection, accommodation or tolerance, to the blood group
      antigen. The studies on immune response to incompatible alpha-gal epitopes have
      further indicated that tolerance to incompatible blood group antigens can be
      achieved by gene therapy with autologous bone marrow cells or autologous
      lymphocytes engineered to express the incompatible blood group antigen. Studies
      in the mouse model suggest that administration into the patient such autologous
      cells engineered to express the incompatible transplantation carbohydrate antigen
      induces deletion of anti-blood group B cells and induction of tolerance, provided
      that the anti-blood group antibodies are removed. Such tolerance is perpetuated
      indefinitely by the subsequent transplantation of the organ expressing the
      incompatible blood group antigen.

PMID- 16905362
TI  - Comparative sensitivity of solid phase versus PEG enhancement assays for
      detection and identification of RBC antibodies.
AB  - Blood banks require a sensitive, specific, and efficient method to detect
      clinically significant RBC antibodies. Solid phase antibody screening methods are
      popular due to high sensitivity and automation. However, the high degree of
      reactivity detects "false positive" antibodies of questionable clinical
      significance leading to additional testing. We studied positive rates of Capture
      R vs. PEG methods and categorized RBC antibodies identified by initial test
      results of 33,564 consecutive samples by Capture-R method. Capture-R was positive
      in 1,084/33,564 (3.2%) of samples. Using PEG as our "gold standard", PEG
      confirmed true positivity (i.e., > or = 1 cell reacting) in 710 Capture-R
      positive samples (65.5%); 374 Capture-R positive samples (34.5%) did not react in
      PEG (i.e., false positives). Of the 710 samples with true positivity, only 510
      showed clinically significant alloantibodies. Using PEG as our "gold standard",
      only 2/3 of reactions by Capture-R were considered true positives. Because of
      ease and automation, Capture-R is popular as a screening test, but a more
      specific method may be helpful in order to identify truly significant
      alloantibodies.

PMID- 16905363
TI  - Transcriptional profile of the immune response in the lungs of patients with
      active tuberculosis.
AB  - Despite advances in diagnosis and treatment, Mycobacterium tuberculosis causes
      active disease in about 8 million people worldwide annually. The study of the
      interplay between the host and the pathogen at the site of infection in human TB
      may contribute to elucidate the pathogenesis of the disease. In this work, using
      macroarray technology and real-time PCR, we analyzed the modulation of 847 genes
      encoding immune-inflammatory mediators in BALF samples of patients affected by
      active pulmonary TB (PTB) and control patients affected by non-TB diseases. The
      data show that the PTB milieu contains a complex network of gene activation.
      Different genes with adhesive properties and involved in tissue repair and
      fibrosis were modulated. In TB patients, we observed the up-regulation of
      cytokines, including IFN-gamma and IFN-gamma pathway genes, of several apoptotic
      genes, and of potent transcriptional activators. These findings can contribute to
      elucidate the mechanisms of MTB pathogenicity in humans.

PMID- 16905364
TI  - Use of a stringent dimerizer-regulated gene expression system for controlled BMP2
      delivery.
AB  - Gene therapy using constitutively active viral promoters to drive expression of
      bone morphogenetic proteins (BMPs) has been extensively evaluated as a strategy
      for inducing bone regeneration. However, this approach offers little control over
      the concentration, timing, or duration of BMP synthesis. To gain greater control
      over BMP kinetics, we developed a new inducible system for the controlled
      expression of BMP2 using a two-component transcription factor that is dimerized
      with rapamycin (Rap). This approach provided stringent control over BMP2
      synthesis with no BMP expression detected in the uninduced state. Rapamycin or
      the less immunosuppressive analogue, AP21967, rapidly and reversibly induced BMP2
      in a dose-dependent manner (range 0.1-10 nM). Subcutaneous implants of
      fibroblasts containing the Rap-inducible system in syngeneic C57BL/6 mice were
      highly responsive to ip Rap injection (0.1-1 mg/kg). Peak BMP2 levels were
      detected within 24 h of a single Rap injection and declined to undetectable
      levels after 8-10 days. Alternate-day Rap injections (1 mg/kg) for 6 weeks
      induced subcutaneous ectopic bone formation. Rap-dependent healing of a critical
      sized cranial defect was also achieved using this system. This regulated BMP2
      expression system will be extremely useful for examining the role of timing and
      sequence of BMP delivery on bone regeneration.

PMID- 16905365
TI  - Successful reconstitution of immunity in ADA-SCID by stem cell gene therapy
      following cessation of PEG-ADA and use of mild preconditioning.
AB  - Gene therapy is a promising treatment option for monogenic diseases, but success
      has been seen in only a handful of studies thus far. We now document successful
      reconstitution of immune function in a child with the adenosine deaminase (ADA)
      deficient form of severe combined immunodeficiency (SCID) following hematopoietic
      stem cell (HSC) gene therapy. An ADA-SCID child who showed a poor response to PEG
      ADA enzyme replacement was enrolled into the clinical study. Following cessation
      of enzyme replacement therapy, autologous CD34(+) HSCs were transduced with an
      ADA-expressing gammaretroviral vector. Gene-modified cells were reinfused
      following one dose of preconditioning chemotherapy. Two years after the
      procedure, immunological and biochemical correction has been maintained with
      progressive increase in lymphocyte numbers, reinitiation of thymopoiesis, and
      systemic detoxification of ADA metabolites. Sustained vector marking with
      detection of polyclonal vector integration sites in multiple cell lineages and
      detection of ADA activity in red blood cells suggests transduction of early
      hematopoietic progenitors. No serious side effects were seen either as a result
      of the conditioning procedure or due to retroviral insertion. Gene therapy is an
      effective treatment option for the treatment of ADA-SCID.

PMID- 16905366
TI  - Identification and isolation of embryonic stem cell-derived target cells by
      adenoviral conditional targeting.
AB  - The technical limitations of isolating target cells have restricted the utility
      of pluripotent embryonic stem (ES) cells. For example, early cardiac (i.e.,
      precontractile) cells have not been isolated from ES cells. Here, we find that
      direct expression of reporter genes under cell-specific promoters-the currently
      available strategy for isolating cells lacking cell-specific surface markers-is
      ineffective for isolating progenitor cells. This was due to the weak activity of
      cell-specific promoters, particularly in ES cells at early stages. We show that
      adenoviral conditional targeting efficiently isolates viable ES cell-derived
      target cells without harmful effects. In this strategy, we employ the alpha
      myosin heavy chain and Nkx2.5 promoter to visualize and purify efficiently
      differentiated and primitive cells of the cardiac lineage, respectively. While
      the former cells predominantly expressed sarcomeric proteins and maintained
      contractile function, the latter demonstrated neither of these features, but
      rather exhibited expression patterns characteristic of a mixture of primitive
      cells and cardiomyocytes. Interestingly, smooth muscle actin was predominantly
      expressed in the latter cells, and both functionally known and unknown genes were
      systematically identified, demonstrating the benefits of this system. Thus, our
      method facilitates molecular and cellular studies of development and ES cell
      derived cell therapy.

PMID- 16905367
TI  - Postictal autoscopy in a patient with partial epilepsy.
AB  - Autoscopy is an experience of seeing oneself in external space, viewed from
      within one's own physical body. It is a complex psycho-sensorial hallucinatory
      perception of one's own body image projected into external visual space, with
      epilepsy one of the common disorders reported to be associated with the
      experience. A survey of the literature revealed that there are few case reports
      of postictal autoscopic phenomena. Herein, we report a case of a patient with
      partial epilepsy who has experienced postictal autoscopy for nearly 30 years.
      Although the neurological mechanisms that cause autoscopic phenomena are not
      fully understood, wish-fulfilling fantasies released as a result of a shaken
      integrity regarding personal bodily image may contribute to the shaping of the
      symptoms, at least in the case of postictal autoscopy.

PMID- 16905368
TI  - Detection of hypoxia-related proteins in medaka (Oryzias latipes) brain tissue by
      difference gel electrophoresis and de novo sequencing of 4-sulfophenyl
      isothiocyanate-derivatized peptides by matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry.
AB  - Two-dimensional fluorescence-based difference gel electrophoresis (DIGE) was used
      in combination with matrix-assisted laser desorption/ionization tandem time-of
      flight mass spectrometry (MALDI-TOF/TOF-MS) to identify a set of hypoxia-related
      biomarker proteins in medaka (Oryzias latipes) brain tissue. Each of the proteins
      were identified via de novo sequencing of tryptic peptides derivatized with 4
      sulfophenyl isothiocyanate (SPITC), which N-terminally sulfonates peptides and
      promotes facile post-source decay peptide fragmentation, resulting in greatly
      simplified spectra consisting mainly of y-series fragment ions. We also report
      that addition of the non-ionic surfactant n-octyl-beta-d-glucopyranoside
      significantly improves SPITC-derivatized peptide recoveries. In addition, we
      found that a MALDI matrix consisting of the sodium-tolerant matrix 2,4,6
      trihydroxyacetophenone, diammonium citrate, and alpha-cyano-4-hydroxycinnamic
      acid also improves ionization of SPITC-peptides, presumably by reducing
      ionization suppression effects from matrix contaminants, especially sodium
      cations. The DIGE experiments and analyses resulted in detection of six abundant
      proteins and related isozymes up-regulated (>1.49, p<0.005) in hypoxic medaka
      brain tissues, including two hemoglobin beta subunit forms, four carbonic
      anhydrase 2 forms, calbindin, aldolase, succinate dehydrogenase, and glutathione
      S-transferase.

PMID- 16905369
TI  - Are perineal and luminal fistulas associated in Crohn's disease? A population
      based study.
AB  - BACKGROUND & AIMS: We aimed to determine the frequency of fistulizing Crohn's
      disease (CD) and the relationship between perineal and luminal fistulas. METHODS:
      A population-based retrospective study was conducted by using the University of
      Manitoba Inflammatory Bowel Disease Research Registry. In 2003 there were 3192
      IBD patients, 1595 had (CD), and 398 patients reported stricturing or fistulizing
      disease. Patients were interviewed and medical records were reviewed for
      phenotype assessment. Perineal fistulas were defined as those exiting in the
      perineum or fistulizing to sexual organs. Luminal fistulas were defined as
      arising from the bowel to organs other than the perineum. RESULTS: The prevalence
      of fistulizing CD was at most 22.1%. Of the 398 patients, 280 CD patients were
      eligible for full phenotype verification. Of these, 50 patients had both perineal
      and luminal fistulas, 151 had only perineal fistulas, and 79 had only luminal
      fistulas. Odds ratio (OR) for likelihood of having luminal fistula disease if
      perineal disease was present was 5.02 (95% confidence interval [CI], 3.40-7.42; P
      < .0001). Fistula patients were more likely to be diagnosed younger; 20-29 years
      (OR, 1.37; 95% CI, 1.02-1.85; P = .048). Compared with luminal fistulas, perineal
      fistulas had a higher likelihood to have colonic (OR, 3.32; 95% CI, 1.59-6.90; P
      = .002) rather than isolated ileal involvement (OR, 0.39; 95% CI, 0.21-0.72; P =
      .004). The comparison of fistulizing CD to non-fistulizing disease revealed a
      predisposition to colonic (OR, 1.41; 95% CI, 1.04-1.90; P = .032), ileocolonic
      (OR, 2.49; 95% CI, 1.91-3.26; P < .001), and upper gastrointestinal (OR, 3.87;
      95% CI, 1.93-7.74; P < .0001) disease versus isolated ileal involvement (OR,
      0.25; 95% CI, 0.19-0.34; P < .0001). CONCLUSIONS: There is a lower prevalence of
      fistulizing CD in this population than previously published. Perineal and luminal
      fistula diseases are highly related to one another but typically have distinct
      clinical associations.

PMID- 16905370
TI  - Differential influence of iNOS and nNOS inhibitors on rostral ventrolateral
      medullary mediated cardiovascular control in conscious rats.
AB  - We evaluated the cardiovascular effects of nitric oxide (NO) inhibitors
      microinjected into the rostral ventrolateral medulla (RVLM) of conscious rats.
      Application of L-NAME or aminoguanidine (AG) induced an increase in arterial
      blood pressure (MAP) and an increase in heart rate, whereas 7-nitroindazole (7
      NI) decreased MAP and HR. Microinjection of glutamate produced an increase in MAP
      which was followed by either a tachycardia or a bradycardia. Such responses were
      blocked totally by prior administration of L-NAME and attenuated (approximately
      50%) by 7-NI. In contrast, glutamate responses were enhanced by following AG. We
      conclude that in conscious rats, NO has tonic effects in the RVLM and may
      participate in the modulation of the actions of glutamate through iNOS and nNOS
      pathways.

PMID- 16905371
TI  - The continuing problem of post chemotherapy nausea and vomiting: contributions of
      classical conditioning.
AB  - Despite continuing improvements in antiemetic therapies, nausea and vomiting
      following chemotherapy treatments for cancer remain significant clinical problems
      for many patients. The role of classical conditioning in patients' anticipatory
      nausea is well known, but little attention has been paid to possible conditioning
      effects on post treatment nausea. The present study statistically examined the
      contribution of anticipatory (conditioned) nausea to patients' subsequent post
      treatment nausea. Forty early stage breast cancer patients who developed
      anticipatory nausea were analyzed. Results revealed a significant correlation
      between the intensity of anticipatory nausea in the clinic prior to their
      treatment infusion and subsequent post treatment nausea during the 24 h after the
      infusion. These results provide support for the hypothesis that, once
      established, conditioned nausea may contribute to the severity of subsequent post
      treatment nausea in patients receiving repeated cycles of chemotherapy for
      cancer. The results suggest the importance of considering the contribution of
      conditioning process to nausea and other post treatment side effects.

PMID- 16905372
TI  - Compensatory mechanisms in the aging motor system.
AB  - Motor functions decline with age due to a number of factors. There is interest in
      whether these changes are reflected in the organisation of the cerebral motor
      system in older subjects and whether such changes might be in some way
      compensatory. Most studies in humans have used functional brain imaging
      techniques to compare motor system activation in younger and older subjects.
      Interpretation of these results is made more difficult by potential neurovascular
      changes in older subjects. However, in general, there appears to be greater motor
      task-related brain activity in a wider network of brain regions in older compared
      to younger subjects. The evidence that these changes are compensatory in nature
      is less clear. Incorporation of behavioural and anatomical data will be required
      in order to fully interpret the functional imaging results.

PMID- 16905373
TI  - Equal and local-load-sharing micromechanical models for collagens: quantitative
      comparisons in response of non-diabetic and diabetic rat tissue.
AB  - Chemical crosslinks in collagens resulting from binding of advanced glycation end
      products, have long been presumed to alter the stiffness and permeability of
      glycated tissues. Recently, we developed a stochastic mechanical model for the
      response and failure of uniaxially deformed sciatic nerve tissue from diabetic
      and control rats. Here, we use our model to determine the likely correlation of
      fibril glycation with failure response, by quantifying statistical differences in
      their response. Our four-parameter model describes both the non-linear toe region
      and non-linear failure region of these tissues; the four parameters consist of
      (1) collagen fibril alignment, (2) fiber bundle waviness, (3) Weibull shape
      parameter for fibrillar strength, and (4) modulus-normalized Weibull scale
      parameter for fibrillar strength. Using an equal load sharing model we find that
      diabetic and control tissues had shape parameters of 9.88+/-5.50 and 4.33+/-3.67
      (p=0.043), respectively, and scale parameters of 0.28+/-0.07 and 0.58+/-0.25
      (p=0.033), respectively, implying that the diabetic tissue behaves in a more
      brittle manner, consistent with more highly crosslinked fibrils. We conclude that
      biochemical crosslinking directly affects measured mechanical properties.
      Further, this mechanical characterization may prove useful in mapping alterations
      in stiffness and permeability observed in glycated tissues.

PMID- 16905374
TI  - Submicroscopic unbalanced translocation resulting in del10p/dup13q detected by
      subtelomere FISH.
AB  - Chromosomal rearrangements involving the (sub)telomeres are an important cause of
      human genetic diseases: with the development of advanced molecular cytogenetic
      methods they have been identified as a major cause of mental retardation and/or
      congenital malformation syndromes. We identified a cryptic unbalanced de novo
      translocation 10p/13q by subtelomere FISH in a boy with mental and growth
      retardation (karyotype: 46,XY,der(10)t(10;13)(p15.1;q34)(D10S2488-,D13S296+)).
      Craniofacial dysmorphisms included frontal bossing, epicanthal folds, long
      philtrum, thin upper lip, short nose, mild retrognathy and a flat midface. In
      addition the patient had ASDII, a pyloric stenosis, bilateral inguinal hernias
      and cryptorchidism. His psychomotor development was significantly delayed.
      Microsatellite typing revealed the paternal origin of the two chromosomes
      involved in the rearrangement. By comparing our case with previously published
      patients with similar aberrations we conclude that the congenital malformations
      in our case are associated with the partial 10p deletion. The craniofacial
      features might be attributed to the 13q duplication. The identification of a
      10p/13q translocation in our case highlights the importance of searching for
      cryptic subtelomeric imbalances in mentally retarded patients and helps to
      further delineate genotype-phenotype correlations in rare chromosomal
      disturbances.

PMID- 16905375
TI  - Changes in the serum sex steroids, IL-7 and RANKL-OPG system after bone marrow
      transplantation: influences on bone and mineral metabolism.
AB  - This study prospectively investigated the changes of the serum levels of the sex
      steroids, IL-7, soluble receptor activator of nuclear factor kappaB ligand
      (sRANKL) and osteoprotegerin (OPG) in bone marrow transplantation (BMT)
      recipients. This study also examined whether the changes of these cytokine levels
      and sex steroids actually influence bone turnover and post-BMT bone loss by
      correlation analysis. Data were analyzed from 39 patients (33.6+/-6.4 years, 19
      men and 20 women) who had DXA performed before BMT and at 1 year after BMT. The
      bone turnover markers, sex steroids and the cytokine levels were measured before
      BMT and serially after BMT. The mean bone loss in the lumbar spine and the total
      proximal femur was 5.9% (P < 0.01) and 11.3% (P < 0.01), respectively. During the
      immediate post-BMT period, bone formation decreased, whereas the bone resorption
      increased. For the female recipients, the estradiol levels declined at 1 week
      after BMT, and they did not recover to the basal levels. For the male recipients,
      the testosterone levels decreased at 1 week and then it increased to its baseline
      level. The IL-7 levels reached their maximum at 1 week and then declined to
      baseline level by 3 months. The serum sRANKL, OPG levels and the sRANKL/OPG ratio
      showed their peak at post-BMT 3 weeks. The mean daily dose of steroid was
      associated with suppressed bone formation, enhanced bone resorption and increased
      sRANKL levels. The IL-7 levels were also noted to be either positively correlated
      with the levels of ICTP or they were negatively correlated with the levels of
      osteocalcin at 1 and 3 weeks after BMT. Bone loss at the lumbar spine and the
      proximal femur was influenced by the decreased sex steroids and increased IL-7
      levels. During the observation period, the IL-7 levels showed positive
      correlations with the sRANKL levels and the sRANKL/OPG ratio. For the female
      patients, the serum IL-7 levels were negatively associated with the estradiol
      levels at 1 and 3 weeks after BMT. All these findings suggest that IL-7 plays an
      important role for post-BMT bone loss, and this possibly happens via the RANKL
      pathway. These data also suggest that the up-regulation of IL-7 during the early
      post-BMT period may result from a deficiency of estrogen.

PMID- 16905376
TI  - Evaluation of fetal bone structure and mineralization in IGF-I deficient mice
      using synchrotron radiation microtomography and Fourier transform infrared
      spectroscopy.
AB  - The role of insulin like growth factor-I (IGF-I) during pre-natal development has
      not been evaluated in detail. However, the high degree of growth retardation and
      peri-natal mortality in IGF-I deficient mouse models indicates that it plays a
      critical role during this time. Techniques to assess the structure and quality of
      bone in small animal fetuses could be beneficial in better understanding its role
      in bone metabolism and skeletal development. Synchrotron microtomography (SR
      microCT) and Fourier transform infrared spectroscopy (FTIR) may provide methods
      to visualize and quantify differences in the structure and mineral density of
      bone in small animal fetuses. Tibia and spine from IGF-I deficient and wildtype
      fetal mice (18th day gestation) were imaged using SR-microCT. Three-dimensional
      structural indices and the degree of mineralization were determined for each
      sample. Mineralization was also assessed using FTIR and von Kossa staining. Bone
      volume was systematically lower in IGF-I -/- animals (tibia: -15%, p<0.05) while
      both sites were found to have a more rod-like architecture (24%, p<0.05; 113%,
      p<0.01) and lower trabecular separation (-16%, p<0.05; -21%, p<0.05). These
      structural results were mostly consistent with those seen in adult models of IGF
      I deficiency. The degree of mineralization as measured by SR-microCT was higher
      in the IGF-I tibial metaphysis (11.7%, p<0.0001), while FTIR of the whole bone
      showed mineralization to be lower in the knockout group (-11%, p<0.05).
      Interestingly, von Kossa staining revealed no mineral content in the IGF-I -/-
      spinal ossification center while SR-microCT clearly indicated the presence of
      highly attenuating components, if somewhat lower in IGF-I -/- animals (-2.2%,
      p<0.05). This indicates that IGF-I deficiency is linked to subtle differences in
      the mineral environment and mineralization progression. The advantages unique to
      SR-microCT allow for 3D visualization and quantification of pre-natal bone
      microstructure and mineral density in mice which was not previously possible.

PMID- 16905378
TI  - New directions in the treatment of infected pleural effusion.
AB  - The optimum management of patients with parapneumonic effusion and empyema
      remains uncertain. This article will review the evidence and current opinion on
      the pathophysiology of this disease, the role of fibrinolytic therapy, and the
      use of modern surgical techniques.

PMID- 16905379
TI  - Which radiological investigations should be performed to identify fractures in
      suspected child abuse?
AB  - AIMS: To determine which radiological investigations should be performed and
      which children should be investigated. MATERIALS AND METHODS: An all language
      literature search of original articles; from 1950-October 2005. Two reviewers
      independently reviewed each article. A third was carried out on disagreement.
      Each study was assessed using standardised data extraction, critical appraisal
      and evidence forms. RESULTS: Thirty-four studies were included. Fifteen addressed
      the question: which investigation has a higher yield, skeletal surveys (SS) or
      bone scintigraphy (BS)? Studies gave conflicting results. Overall neither
      investigation is as good as the two combined. BS predominately missed skull,
      metaphyseal and epiphyseal fractures, whereas SS commonly missed rib fractures.
      Two studies showed that a repeat SS 2 weeks after the initial study provided
      significant additional information about tentative findings, the number and age
      of fractures. A comparative study evaluated additional oblique views of ribs in
      73 children and showed improved diagnostic sensitivity, specificity and accuracy.
      Four studies addressed the diagnostic yield for occult fractures with respect to
      age. This was significant for children under 2-years old. CONCLUSIONS: In
      children under 2-years old, where physical abuse is suspected, diagnostic imaging
      of the skeleton should be mandatory. SS or BS alone is inadequate to identify all
      fractures. It is recommended that all SS should include oblique views of the
      ribs. This review suggests that the following options would optimize the
      diagnostic yield. However, each needs to be evaluated prospectively: SS that
      includes oblique views, SS and BS, a SS with repeat SS or selected images 2 weeks
      later or a BS plus skull radiography and coned views of metaphyses and epiphyses.

PMID- 16905380
TI  - Imaging of hepatic infections.
AB  - Imaging plays a significant role in the detection, characterization and treatment
      of hepatic infections. Infectious diseases of the liver include pyogenic and
      amoebic abscesses and parasitic, fungal, viral and granulomatous infections. With
      increases in worldwide travel, immunosuppression and changing population
      demographics, identification of cases of hepatic infection is becoming more
      common in daily practice. Knowledge of the imaging features seen with hepatic
      infections can assist in early diagnosis and timely initiation of appropriate
      therapy. This review presents the imaging appearances of hepatic infections,
      emphasizing specific features that may contribute to the diagnosis. Examples of
      the imaging findings seen with pyogenic and amoebic abscesses, infection with
      Echinococcus granulosus (Hydatid), schistosomiasis, candidiasis and tuberculosis
      (TB) are presented.

PMID- 16905382
TI  - Computer-assisted detection for CT colonography: external validation.
AB  - AIM: To externally validate a computer-assisted detection (CAD) system for
      computed tomography (CT) colonography, using data from a single centre uninvolved
      with the software development. MATERIALS AND METHODS: Twenty-five multi-detector
      CT colonography examinations of patients with validated polyps accumulated at a
      single centre were examined by two readers who used endoscopic and
      histopathological data to identify polyp coordinates. A CAD system that had been
      developed using data from elsewhere, and had not previously encountered the
      present data, was then applied to the data at sphericity filter settings of 0.75
      and 0.50 and identified potential polyps. True-positive, false-negative, and
      false-positive counts were determined by comparison with the known polyp
      coordinates. RESULTS: Twenty-five patients had 57 polyps, median size 6mm (range
      1-15mm). Per-patient sensitivity for the CAD system was 96% (24 of 25). The CAD
      system detected 44 (77%) polyps at sphericity setting 0.75 and 49 (86%) polyps at
      sphericity 0.50: the additional five polyps detected all measured 5mm or less.
      Sphericity of 0.75 resulted in a median of 10 (one to 34) easily dismissed false
      positive prompts per patient and a median of 4 (zero to 15) that needed three
      dimensional rendering before dismissal. This rose to 32 (16 to 99) and 11 (three
      to 35), respectively, at sphericity 0.5. CONCLUSIONS: A per-patient sensitivity
      of 96% was found for the CAD system (in patients with a median polyp diameter of
      6mm) using external validation, a more stringent test than either internal cross
      validation or temporal validation. Decreasing sphericity increases sensitivity
      for small polyps at the expense of decreased specificity.

PMID- 16905384
TI  - High-resolution magnetic resonance cholangiography (MRC) with adaptive averaging:
      diagnostic performance evaluation.
AB  - AIM: To evaluate the diagnostic performance of an interactive, adaptively
      averaged (AA) two-dimensional (2D) magnetic resonance cholangiography (MRC)
      technique in patients with suspected biliary disease by comparison to the
      standard MRC technique. MATERIALS AND METHODS: The AA 2D MRC method registers the
      images after acquisition, allowing summation of multiple images to improve the
      signal:noise ratio (SNR) and thereby potentially improve the visualization of
      bile ducts. One hundred and twenty-eight patients underwent both 2D conventional
      and AA magnetic resonance cholangiopancreatography (MRCP). Twenty-seven patients
      were excluded from the analysis as AA images could not be properly obtained due
      to technical failures. All examinations were performed using a 1.5 T whole-body
      MR system and a four-channel torso phased array coil. Images of 101 patients were
      adaptively averaged using an in-house developed program written in IDL. Two
      readers qualitatively evaluated the studies in consensus, blinded to acquisition
      details and without knowledge of clinical information. RESULTS: The AA technique
      was significantly better than the conventional 2D MRC for the visualization of
      the second-order branch intrahepatic ducts (p<00001). Overall, there was no
      significant difference in the diagnostic confidence between two techniques
      (p=0.12). However, the AA technique showed a trend towards more confident
      diagnosis of biliary strictures (p=0.055), likely due to better diagnostic
      confidence in identifying second order branch intrahepatic duct strictures
      (p=0.054). CONCLUSION: Excluding those patients those patients in whom either
      satisfactory respiratory gating or a suitable kernel placement was not achieved,
      AA 2D MRC demonstrated a significant improvement in visualization of intrahepatic
      duct branches compared to standard MRC.

PMID- 16905381
TI  - 16-detector row computed tomographic coronary angiography in patients undergoing
      evaluation for aortic valve replacement: comparison with catheter angiography.
AB  - AIM: To evaluate the diagnostic accuracy of 16-detector row computed tomography
      (CT) in assessing haemodynamically significant coronary artery stenoses in
      patients under evaluation for aortic stenosis pre-aortic valve replacement.
      SUBJECTS AND METHODS: Forty consecutive patients under evaluation for severe
      aortic stenosis and listed for cardiac catheterization before potential aortic
      valve replacement underwent coronary artery calcium (CAC) scoring and
      retrospective electrocardiogram (ECG)-gated multi-detector row computed
      tomographic coronary angiography (MDCTA) using a GE Lightspeed 16-detector row CT
      within 1 month of invasive coronary angiography (ICA) for comparative purposes.
      All 13 major coronary artery segments of the American Heart Association model
      were evaluated for the presence of > or =50% stenosis and compared to the
      reference standard. Data were analysed on a segment-by-segment basis and also in
      "whole patient" terms. RESULTS: A total of 412/450 segments from 35 patients were
      suitable for analysis. The overall accuracy of MDCTA for detection of segments
      with > or =50% stenosis was high, with a sensitivity of 81.3%, specificity 95.0%,
      positive predictive value (PPV) 57.8%, and negative predictive value (NPV) 98.4%.
      On a "whole-patient" basis, 100% (19/19) of patients with significant coronary
      disease were correctly identified and there were no false-negatives. Excluding
      patients with CAC >1000 from the analysis improved the accuracy of MDCTA to:
      sensitivity 90%, specificity 98.1%, PPV 60%, NPV 99.7%. CONCLUSION: Non-invasive
      16-detector row MDCTA accurately excludes significant coronary disease in
      patients with severe aortic stenosis undergoing evaluation before aortic valve
      replacement and in whom ICA can therefore be avoided. Its segment-by-segment
      accuracy is improved further if CAC>1000 is used as a gatekeeper to MDCTA.

PMID- 16905386
TI  - Intraductal papillary mucinous tumour of the pancreas: differentiation of
      malignancy and benignancy by CT.
AB  - AIM: To retrospectively identify signs predictive of malignant intraductal
      papillary mucinous tumour (IPMT) of the pancreas on computed tomography (CT)
      images. MATERIALS AND METHODS: Thirty-four benign and 21 malignant pancreatic
      IPMTs were evaluated. Preoperative helical CT images in these 55 cases of
      pathologically proven pancreatic IPMT were reviewed by two radiologists unaware
      of the histological grading. Tumour morphological types, locations, numbers and
      sizes of cystic lesions, maximum main pancreatic duct diameters, the presence of
      septa, mural nodule, wall thickening, and calcification in cysts, communication
      with the main pancreatic duct, peripancreatic haziness, protrusion of duodenal
      papilla, pancreatic atrophy, lymphadenopathy and distant metastasis were analysed
      using univariate and multivariate analysis. RESULTS: Main duct IPMTs were more
      likely to be malignant (71%) than branch duct (23%) or combined type IPMTs (28%;
      p=0.002). Among the branch duct type and combined types, large cystic lesion
      (p=0.018), the presence of a mural nodule (p=0.018), a thickened wall (p=0.009),
      and peripancreatic haziness (p=0.039) were found to predict malignancy.
      CONCLUSION: CT is helpful in the preoperative differentiation of malignant and
      benign pancreatic IPMT. The presence of a dilated main pancreatic duct, mural
      nodules, thickened wall and peripancreatic haziness may be used as independent
      predictive signs of malignancy.

PMID- 16905385
TI  - Diagnostic accuracy of CT-guided percutaneous cutting needle biopsy for thymic
      tumours.
AB  - AIM: To determine the diagnostic accuracy of computed tomography (CT)-guided
      percutaneous cutting needle biopsy (PCNB) for thymic tumours in accordance with
      the World Health Organization (WHO) classification. MATERIAL AND METHODS: We
      retrospectively analysed a consecutive series of 138 cases in which CT-guided
      PCNB had been performed for an anterior mediastinal tumour. Its sensitivity and
      specificity for thymic epithelial tumours were evaluated, and the concordance
      between the histopathological diagnosis according to the WHO classification of
      thymic tumours based on PCNB and the diagnosis is based on the surgical specimens
      was assessed by Kappa statistic. RESULTS: The diagnostic sensitivity and
      specificity of CT-guided PCNB for thymic tumours were 93.3 and 100%,
      respectively. The overall concordance between the diagnosis according to the WHO
      classification established by PCNB specimen and by the surgical specimen was
      79.4% (weighted kappa=0.79). CONCLUSION: CT-guided PCNB is a reliable method of
      diagnosing thymic tumours, and there was good concordance for the WHO
      classification between the diagnosis based on CT-guided PCNB specimen and that
      based on the surgical specimen.

PMID- 16905387
TI  - Radiological findings of screen-detected cancers in a multi-centre randomized,
      controlled trial of mammographic screening in women from age 40 to 48 years.
AB  - AIM: To elucidate the mammographic findings of screen-detected cancers in women
      screened between 40-48 years, and to establish the frequency and nature of
      abnormal findings on previous mammograms in women with screen-detected cancers.
      METHODS: A radiology review panel consisting of three experienced breast
      radiologists viewed the screening mammograms in chronological order, confirming
      that any abnormalities detected corresponded to the cancers detected at later
      screens. An analysis correlating mammographic features with median invasive size
      and the proportion measuring less than 10 and 15mm was performed. RESULTS: Two
      hundred and thirty-two women had screen-detected invasive cancers with mammograms
      available for review. The most frequent features seen at diagnosis were spiculate
      mass, ill-defined mass, granular calcification, deformity and comedo
      calcification. Thirty-four percent of mammograms showed calcification. The
      mammographic sign associated with smallest median size was calcification.
      Calcification was also the mammographic abnormality most frequently associated
      with cancers <10mm in size. In total there were 147 abnormal previous screens of
      87 women. The most commonly missed features were granular microcalcification,
      deformity and ill-defined mass. Of the missed abnormalities 20% were classified
      as malignant, 43% as subtle change and 32% as non-specific. CONCLUSION: Compared
      with older women, screen-detected cancer in younger women more commonly manifests
      as calcification and less frequently a spiculate mass. Calcification is the sign
      most frequently associated with invasive cancers <10mm in size. Calcification and
      deformity are the signs most frequently seen on the previous mammograms of women
      with screen-detected cancer.

PMID- 16905388
TI  - Specimen radiography as predictor of resection margin status in non-palpable
      breast lesions.
AB  - AIM: This study aimed to evaluate the role of specimen radiography in predicting
      margin status for non-palpable breast malignancies. METHODS: We retrospectively
      reviewed the clinical and pathological data together with specimen radiographs of
      164 women with ductal carcinoma in situ, who were referred to our centre between
      January 1997 and December 2000. In all cases microcalcifications were discovered
      on mammography. Lesions were localized preoperatively using a guide-wire.
      Specimen radiography findings and clinicopathological data were correlated with
      pathological findings. RESULTS: Findings comprised 122 pure ductal carcinomas in
      situ (74%) and 42 mixed carcinomas, both infiltrating and in situ (26%). On the
      specimen radiographs, the lesions were close (<1mm) to one edge of the lumpectomy
      in 34 (21%) cases. Histologically, there were 103 positive resection margins
      (<1mm, 63%) and only 61 negative margins (> or =1mm, 37%). On univariate
      analysis, factors associated with positive resection margins were found to be
      distance from microcalcifications to edge of lesion on specimen radiographs, and
      radiological multifocality. On multivariate analysis (logistic regression), a
      radiological margin <5mm and multifocality were the only risk factors for close
      histological margins. Radiological margins were not associated with surgical
      findings. CONCLUSION: Our results demonstrate that there is a correlation between
      specimen radiographs and histological results. The clinical relevance of this
      should be evaluated in a prospective study.

PMID- 16905389
TI  - The effect of temperature reduction on cement working time in percutaneous
      vertebroplasty.

PMID- 16905390
TI  - Comparison between radiofrequency ablation and percutaneous microwave coagulation
      therapy for small hepatocellular carcinomas.

PMID- 16905392
TI  - Sexual obsessions and clinical correlates in adults with obsessive-compulsive
      disorder.
AB  - Because little is known about sexual obsessions in individuals with obsessive
      compulsive disorder (OCD), we examined rates and clinical correlates of sexual
      obsessions in 293 consecutive subjects with primary lifetime Diagnostic and
      Statistical Manual of Mental Disorders, Fourth Edition, OCD (54.6% females; mean
      age, 40.5 +/- 12.9 years). Symptom severity was examined using the Yale-Brown
      Obsessive Compulsive Scale. Comorbidity, treatment response, insight, depression
      symptoms, quality of life, and social functioning were also assessed. All
      variables were compared in subjects who have OCD with and without sexual
      obsessions. Of the 293 subjects with primary OCD, 73 (24.9%) reported a history
      of sexual obsessions, and 39 (13.3%) of the subjects with OCD reported current
      sexual obsessions. Women were as likely as men to report sexual obsessions. As
      compared to those without these symptoms, subjects with current sexual obsessions
      were significantly more likely to report current aggressive (P < .001) and
      religious (P = .001) obsessions. Subjects with sexual obsessions also reported an
      earlier age of onset of OCD than subjects without these symptoms. Severity of
      OCD, comorbidity, treatment response, insight, depressive symptoms, quality of
      life, and social functioning did not differ between those with and without sexual
      obsessions. These preliminary results suggest that sexual obsessions are fairly
      common among individuals with OCD and may be associated with important clinical
      characteristics.

PMID- 16905393
TI  - Is current alcohol consumption associated with increased lifetime prevalence of
      major depression and suicidality? Results from a pilot community survey.
AB  - OBJECTIVE: Alcohol use disorders are associated with increased illness severity
      and suicidality in major depressive disorder (MDD). However, little is known
      about how alcohol use across the continuum relates to MDD. METHOD: Subjects were
      496 adults (201 men, 295 women) who completed a community-based telephone survey
      that incorporated a validated structured diagnostic interview for depression and
      a validated alcohol questionnaire. Subjects were divided into 3 alcohol
      consumption groups based on Canadian low-risk drinking guidelines: minimal (MIN),
      moderate (MOD), and heavy (HVY) alcohol consumption. RESULTS: Among subjects with
      MDD, drinking group was not associated with measures of disability, health
      service use, or life satisfaction. Among all women, the prevalence of depression
      increased significantly across drinking groups (MIN, 24.6%; MOD, 30.3%; HVY,
      44.0% [linear-by-linear association chi(2) = 4.1, df = 1, P < .05]), as did the
      prevalence of suicidality among women with MDD (MIN, 16.3%; MOD, 29.6%; HVY,
      45.5% [chi(2) = 4.5, df = 1, P < .05]). CONCLUSION: A range of alcohol
      consumption, not just heavy drinking, may be associated with major depression and
      suicidality.

PMID- 16905395
TI  - Associations between age of onset and lifetime history of panic attacks and
      alcohol use, abuse, and dependence in a representative sample.
AB  - OBJECTIVE: The present investigation evaluated associations between lifetime
      panic attacks and lifetime alcohol use, abuse, and dependence. Specifically, the
      relations between lifetime panic attacks and alcohol use, abuse, and dependence
      were examined after controlling for theoretically relevant variables of comorbid
      psychopathology and polysubstance use. DESIGN AND SETTING: Data for this study
      were obtained from a large statewide survey, the Colorado Social Health Survey.
      Participants were contacted using randomly sampled household addresses (response
      rate was 72%) and interviews took place in participants' homes. PARTICIPANTS: The
      study consisted of a representative sample of the Colorado general adult
      population (n = 4,745; 52% women). MAIN OUTCOME MEASURES: The Diagnostic
      Interview Schedule (American Psychiatric Association. Diagnostic and Statistical
      Manual of Mental Disorders [3rd ed]. Washington [DC]: Author. 1980) was
      administered to obtain Axis I diagnoses. RESULTS: After controlling for
      theoretically relevant variables of comorbid psychopathology and polysubstance
      use, a lifetime history of panic attacks was significantly associated with
      alcohol dependence but not alcohol use or abuse. In addition, among participants
      reporting a lifetime history of both panic attacks and alcohol abuse or
      dependence, the number of participants for whom panic attacks developmentally
      preceded the onset of alcohol use problems was significantly greater (85.5%) than
      the number of participants for whom alcohol use problems preceded the onset of
      panic attacks (13.4%) or the number of participants for whom these problems
      developed at the same age (2.2%). CONCLUSIONS: These data suggest panic attacks,
      particularly of early onset, may serve as a risk marker for alcohol dependence.

PMID- 16905394
TI  - Lifetime rhythmicity and mania as correlates of suicidal ideation and attempts in
      mood disorders.
AB  - BACKGROUND: The aim of this study is to establish to what degree variation in
      lifetime experience of rhythmicity and manic-hypomanic features correlates with
      suicidality in individuals with mood disorders and other major psychiatric
      diagnoses and in a comparison group of controls. METHOD: Suicidal ideation and
      attempts were investigated in a clinical sample, including 77 patients with
      schizophrenia, 60 with borderline personality disorder, 61 with bipolar disorder,
      88 with unipolar depression, and 57 with panic disorder, and in a comparison
      group of 102 controls. Using information derived from the diagnostic interview
      and a self-report assessment of mood spectrum symptoms, subjects were assigned to
      3 categories according to the maximum level of suicidality achieved in the
      lifetime (none, ideation/plans, and suicide attempts). The association of
      categorical and continuous variables with suicidality levels was investigated
      using multinomial logistic regression models. RESULTS: Suicidal ideation and
      plans were more common in unipolar depression (50%) and bipolar disorder (42.4%)
      than in borderline personality disorder (30%), whereas the reverse was true for
      suicidal attempts. In each of the study groups, the number and the type of mood
      spectrum items endorsed, including depressive and manic-hypomanic items and
      rhythmicity and vegetative symptoms, were associated with increased levels of
      suicidality. CONCLUSIONS: Our results suggest that the assessment of lifetime
      rhythmicity and manic-hypomanic features may be clinically useful to identify
      potential suicide attempters in high-risk groups.

PMID- 16905396
TI  - The dimensional assessment of personality in pathologic and social gamblers: the
      role of novelty seeking and self-transcendence.
AB  - OBJECTIVE: A few personality traits are characteristic of pathologic gamblers
      (PGs), but it is not clear if and how their personality profile differs from that
      of non-pathologic gamblers (non-PGs). METHODS: Sixty-five non-clinical subjects,
      differentiated into non-PGs and PGs with the means of the South Oak Gambling
      Screen (SOGS) and Diagnostic and Statistical Manual of Mental Disorders-Fourth
      Edition-Text Revision (DSM-IV-TR) criteria, were administered with the
      Temperament and Character Inventory; their values were compared with those of
      control subjects (CS). RESULTS: Novelty seeking (NS) and self-transcendence (ST)
      values were higher whereas self-directedness and cooperativeness values were
      lower in PGs with respect to both non-PGs and CS. A positive correlation was
      noted between SOGS score and NS (r = 0.40) and ST (r = 0.50) values, as well as a
      significant positive dependence between SOGS score and a family history of
      gambling (t = 2.816; P = .007). The subsamples of PGs reporting a parental
      involvement in gambling showed higher NS than the remaining PGs. CONCLUSIONS:
      Specific temperamental and character dimensions, especially NS and ST,
      differentiated PGs from both non-PGs and CS; the identification of a personality
      profile at risk for problem gambling may represent an important predictor of
      outcome and constitute a possible target for specific treatment approaches.

PMID- 16905397
TI  - Symptom correlates of posttraumatic stress disorder in clients with borderline
      personality disorder.
AB  - Limited research has examined the clinical and functional impact of concurrent
      posttraumatic stress disorder (PTSD) in people with borderline personality
      disorder (BPD). Such information is particularly lacking for BPD clients with the
      most disabling symptoms: those who meet criteria for severe and persistent mental
      illness. We evaluated individuals with severe mental illness to assess whether
      PTSD in individuals with BPD was associated with more severe symptoms and
      impaired functioning than BPD alone and replicated these findings in an
      independent sample. In both the studies, the clients with PTSD and BPD reported
      significantly higher levels of general distress, physical illness, anxiety, and
      depression than those with BPD alone. Because individuals with both of these
      disorders are likely to require more intensive clinical services to reduce
      distress and improve functioning, work is needed to develop and evaluate
      interventions designed to address these comorbid conditions.

PMID- 16905399
TI  - The interrater reliability of the Structured Interview for DSM-IV Personality.
AB  - We examined the joint interview interrater reliability of the Structured
      Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth
      Edition, Personality Disorders (SIDP-IV) in 433 non-treatment-seeking military
      recruits. Reliability was computed for the diagnosis of a specific personality
      disorder (PD) and for the number of PD criteria present, and computed using a
      dimensional score. Reliability increased when PDs were computed using dimensional
      scores rather than categorical scores. Avoidant and dependent PDs demonstrated
      the highest interrater reliability, whereas schizoid and schizotypal showed the
      lowest. This large sample allowed us to perform item-level analyses of the SIDP
      IV. Interrater reliability for each of the PD criteria was generally more than
      0.70, with the notable exception of criteria scored through observation only.
      Overall, the SIDP-IV demonstrated good reliability in a non-treatment-seeking
      population.

PMID- 16905398
TI  - The long-term outcome of 2 family intervention strategies in schizophrenia.
AB  - The different family-based interventions that have proven to be effective in
      treating people with schizophrenia present some therapeutic elements in common
      and differ in certain other respects, although to date, none of the proposed
      approaches have demonstrated to be clearly superior to each other in reduced
      relapse and readmission rates. Although the approaches based on relatives group
      therapies save considerable amounts of time, some data reveal better short-term
      results when the intervention focuses on the family unit and the participant
      patient. OBJECTIVE: The aim of this study was to determine whether the clinical
      and social benefits observed in the short term would be maintained 5 years later.
      METHOD: Follow-up study over a 5-year period on 87 patients diagnosed with
      schizophrenia and their families taking part in a cognitive behavioral therapy,
      assigned at random either to (a) a family unit including the patient or (b) a
      group of relatives. RESULTS: The statistical contrast between the 2 survival
      curves reveals that they are not significant with regard to relapse (log-rank
      test, 1.30; P < .2538) nor readmissions (long rank test, 0.03; P = .8547).
      Results after analyzing other variables were also similar in both groups, with
      slight differences for the strategy where the patient was not present.
      CONCLUSIONS: Both types of interventions have similar long-term impact with a
      clear tendency to loose benefits acquired during the intervention. This finding
      suggests that it might be possible for some subgroups of patients to conduct a 12
      month therapy followed by a support group, hoping that long-term benefits would
      be maintained.

PMID- 16905400
TI  - An investigation of the validity of the Diagnostic and Statistical Manual of
      Mental Disorders, Fourth Edition avoidant personality disorder construct as a
      prototype category and the psychometric properties of the diagnostic criteria.
AB  - This study investigated several aspects of the validity of the Diagnostic and
      Statistical Manual of Mental Disorders, Fourth Edition avoidant personality
      disorder (APD) construct, with emphasis on the psychometric properties of the
      diagnostic criteria and the prototype nature of the construct. A sample of 1,058
      patients from the Norwegian Network of Psychotherapeutic Day Hospitals was
      examined by means of exploratory factor analysis, correlation, and diagnostic
      efficiency statistics, chi(2) analysis, and frequency distribution. The results
      indicated that APD is a 1-dimensional construct with good internal consistency.
      The criteria had acceptable diagnostic efficiency; criterion 3 performed poorest.
      Number of APD criteria showed no distinct threshold between No-APD and patients
      with APD. Sixty-two different combinations of any 4 APD criteria occurred. It can
      be concluded that the prototype model fitted the data well and that the APD
      diagnostic criteria perform well in the current classification system. The
      Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition hierarchy
      of criteria was not supported.

PMID- 16905402
TI  - Deja vu experiences in patients with schizophrenia.
AB  - To investigate whether deja vu experiences are psychopathologic phenomena, we
      studied the frequency and characteristics of deja vu experiences in patients with
      schizophrenia. One hundred thirteen patients with schizophrenia and 386
      nonclinical control subjects were evaluated with the Inventory of Deja vu
      Experiences Assessment. The frequency and features of deja vu experiences were
      compared between the 2 groups. The patients with schizophrenia had deja vu
      experiences less frequently (53.1%) than did the nonclinical subjects (76.2%).
      The frequency of deja vu experiences did not correlate significantly with age at
      evaluation or education level among the patients with schizophrenia. Most
      characteristics of deja vu experiences of the patients were comparable with those
      of the control subjects. However, the experiences of the patients tended to be
      longer and more monotonous. The patients often felt alert, oppressed, and
      disturbed by the experiences. They appeared to have the experiences under
      unpleasant mental or physical states. Their deja vu experiences are not primarily
      different in nature from those of the nonclinical subjects. The decreased
      frequency of the experiences in the patients may suggest deja vu experiences as
      nonpathologic phenomena.

PMID- 16905401
TI  - Four symptom dimensions in outpatients with schizophrenia.
AB  - OBJECTIVE: The aim of this study was to assess the dimensional structure of the
      Positive and Negative Symptoms Scale (PANSS) to identify the psychopathological
      profiles of outpatients with schizophrenia. METHOD: Two hundred and thirty-one
      persons with schizophrenia (DSM-IV criteria) were randomly selected from a
      register that included all patients under treatment in 5 mental health care
      centers in Spain. Patients were evaluated with a sociodemographic and clinical
      questionnaire, the PANSS, the Disability Assessment Scale short version, and the
      Global Assessment Functioning Scale. A principal component analysis with oblimin
      rotation was used to examine the factor structure of the PANSS. Different
      statistical analyses were done to compare the resulting factors with clinical,
      disability, and social functioning variables. RESULTS: Mean age of patients
      included was 39.6 years and approximately 65% were male. Four principal
      components, each of them with eigenvalues greater than 1.5, accounted for 56.22%
      of the variance. After oblimin rotation, these factors were identified as the
      Negative (32.48%), Excitement (11.29%), Affective (7.45%), and Positive (5.01%)
      components. Significant positive correlation between age and the negative
      dimension was found. Also, we observed significant negative correlations between
      global assessment functioning and negative and positive dimensions. Total
      disability was significantly positively related to all dimensions. CONCLUSION:
      Positive and negative dimensions are common in all principal component analysis
      results, but we also found affective and excitement dimensions. The present
      finding suggests that further investigation of symptom dimensions may help to
      improve symptom-specific treatments; future research should focus on the design
      of new treatment programs considering these results.

PMID- 16905403
TI  - A prospective long-term follow-up study of alexithymia in obsessive-compulsive
      disorder.
AB  - BACKGROUND: Studies evaluating the stability of alexithymia over long follow-up
      periods are rare. We examined the temporal stability of alexithymia in patients
      with obsessive-compulsive disorder (OCD) over 6 years and the association of
      alexithymia with the long-term outcome of OCD. SAMPLING AND METHODS: Of 42
      patients with OCD, 34 (81%) could be reassessed 6 years after inpatient
      treatment. The 20-item Toronto Alexithymia Scale, Yale-Brown Obsessive-Compulsive
      Scale, and Hamilton Depression Rating Scale were used at pretreatment,
      posttreatment, and follow-up. RESULTS: The 20-item Toronto Alexithymia Scale
      total scores and its factors 1 and 2 decreased significantly during follow-up,
      whereas factor 3 remained stable. High correlations of the 20-item Toronto
      Alexithymia Scale total scores (r = 0.84, P < .001) and its 3 factors emerged
      between posttreatment and follow-up, suggesting relative stability over several
      years. Regression analyses (with and without controlling for depressive symptoms)
      showed that higher alexithymia scores did not predict a worse long-term outcome
      of OCD. CONCLUSIONS: Relative stability over such a very long follow-up period
      strongly supports the view that alexithymia is a stable psychologic
      characteristic in patients with OCD. The result that higher alexithymia scores
      were not associated with poorer long-term outcome of OCD might be explained with
      the decrease of alexithymia during treatment and follow-up. However, our sample
      size was small, and further research is clearly required to evaluate the impact
      of changes in alexithymia and its association with the course of OCD.

PMID- 16905404
TI  - Social phobia symptoms: prevalence, sociodemographic correlates, and overlap with
      specific phobia symptoms.
AB  - BACKGROUND: Social phobia (SP) is a highly prevalent disorder in Western
      countries, but is rather rare in Eastern societies. Prevalence rates range from
      0.5% in Eastern samples up to 16% in Western studies. Its prevalence in Israel,
      an Asian state characterized by Western culture, has not yet been studied. The
      present study aimed to assess the prevalence of SP symptoms in a nonclinical
      sample of Israeli adolescents, to characterize sociodemographic correlates of SP
      symptoms and to evaluate comorbidity with specific phobia symptoms. METHODS:
      Participants included 850 young soldiers from the Israel Defense Forces. Measures
      included the Liebowitz Social Anxiety Scale (LSAS; self-report version), a
      questionnaire on specific fears and phobias, and a sociodemographic
      questionnaire. Clinical and demographic correlates of SP were also examined.
      RESULTS: Probable SP (LSAS >or=80) was present in 4.5% of the sample. Overall, SP
      symptoms were reported by a great percentage of the subjects, as displayed by the
      rather high mean LSAS scores (29; SD = 23.79) in this nonclinical sample. The
      following variables were accompanied by higher LSAS scores according to our
      regression model: inability to perform command activities, receiving psychotropic
      medication before army service, having less than two friends, shy family members,
      and treatment during military service. Subjects with probable SP had a rate of
      comorbidity with specific phobia symptoms of 44%. CONCLUSIONS: Our findings
      corroborate those from other studies in Western countries, both regarding the
      high prevalence of SP symptoms and its demographic and clinical correlates, as
      well as regarding the high overlap rate with specific phobia symptoms.

PMID- 16905405
TI  - Borderline personality disorder treated with the conversational model: a
      replication study.
AB  - Recent work has lead to a greater degree of optimism in the treatment of
      borderline personality disorder (BPD). This study looks at a group of patients
      with BPD treated with outpatient psychotherapy using the conversational model of
      Hobson and Meares. The study group is compared, first, with the original cohort
      previously reported by Stevenson and Meares [Stevenson J, Meares R. An outcome
      study of psychotherapy for patients with borderline personality disorder. Am J
      Psychiatry 1992;149(3):358-62] and, second, with a wait-list "treatment-as-usual"
      control group. Patients were recruited well after initiation of the program and,
      hence, can be seen as a group treated under more usual clinical conditions rather
      than as a cohort subject to the initial wave of research enthusiasm. Subjects
      were rated at baseline and 12 months on a range of symptomatic, functional, and
      objective measures. The rate and degree of improvement in the later cohort are
      very similar to the original 1992 cohort and significantly greater than what is
      found in the treatment-as-usual controls. We believe that this is the first
      replication study demonstrating success in treating patients with BPD using an
      established form of individual psychodynamic therapy delivered in an outpatient
      setting.

PMID- 16905407
TI  - Combination antipsychotic therapy in psychiatric outpatient clinics in Taiwan.
AB  - OBJECTIVE: The purpose of this study is to survey the use of combination
      antipsychotic therapy (CAT) in the psychiatric outpatient clinic of a general
      hospital. METHODS: Patients who received at least 2 antipsychotics in the
      psychiatric outpatient clinic of a general hospital in 1 month (August 1-31,
      2003) were identified, and their retrospective chart review was performed. Using
      a questionnaire, we surveyed the clinicians on why 2 antipsychotics were
      prescribed, why long-term CAT was used, and whether the problems were solved by
      CAT. RESULTS: We studied 957 patients diagnosed with schizophrenia and related
      disorders in 1 month. A total of 119 patients (12%) were prescribed at least 2
      antipsychotics. Among these 119 patients, 91 (76%) were prescribed 2 types of
      first-generation antipsychotics (FGAs), and 15 patients (16%) were prescribed a
      second-generation antipsychotic medication and a low-dose FGA medication. The
      clinicians' main reasons for CAT were to treat insomnia (84%) and psychotic
      symptoms (83%). CONCLUSIONS: The results of this study revealed that 12% of the
      patients received CAT in the clinical practice. Most patients were prescribed 2
      FGAs. The clinicians' reasons for prescribing CAT in Taiwan were to treat
      insomnia and psychotic symptoms.

PMID- 16905406
TI  - Interactions between child and parent temperament and child behavior problems.
AB  - OBJECTIVE: Few studies of temperament have tested goodness-of-fit theories of
      child behavior problems. In this study, we test the hypothesis that interactions
      between child and parent temperament dimensions predict levels of child
      psychopathology after controlling for the effects of these dimensions
      individually. METHODS: Temperament and psychopathology were assessed in a total
      of 175 children (97 boys, 78 girls; mean age, 10.99 years; SD, 3.66 years) using
      composite scores from multiple informants of the Junior Temperament and Character
      Inventory and the Achenbach System of Empirically Based Assessment. Parent
      temperament was assessed using the adult version of the Temperament and Character
      Inventory. Statistical analyses included multiple regression procedures to assess
      the contribution of child-parent temperament interactions after controlling for
      demographic variables, other types of child psychopathology, and the individual
      Temperament and Character Inventory and Junior Temperament and Character
      Inventory dimensions. RESULTS: Interactions between child and parent temperament
      dimensions predicted higher levels of externalizing, internalizing, and attention
      problems over and above the effects of these dimensions alone. Among others, the
      combination of high child novelty seeking with high maternal novelty was
      associated with child attention problems, whereas the combination of high child
      harm avoidance and high father harm avoidance was associated with increased child
      internalizing problems. Many child temperament dimensions also exerted
      significant effects independently. CONCLUSIONS: The association between a child
      temperament trait and psychopathology can be dependent upon the temperament of
      parents. These data lend support to previous theories of the importance of
      goodness-of-fit.

PMID- 16905408
TI  - Long-term follow-up study of borderline patients in Japan: a preliminary study.
AB  - To date, only few reports are available regarding the long-term outcome of
      borderline personality disorder (BPD) in Japan. We conducted a retrospective
      follow-up study on the long-term outcome and predictive factors of BPD in Japan.
      Of 72 patients who received treatment at Fukuoka University Hospital between 1973
      and 1989 and met the Diagnostic and Statistical Manual of Mental Disorders,
      Fourth Edition, criteria for BPD retrospectively, 19 patients (26.4%) were
      followed up. We evaluated global outcome at follow-up using the Global Assessment
      of Functioning Scale scored from a completed self-reported questionnaire. The
      mean Global Assessment of Functioning score was 60.7, which meant fair to good
      functioning. The suicide rate was 6.9% (5/72). Using a logistic regression model,
      overinvolvement in family relationships and the number of medical facilities
      where patient was previously treated predicted poor outcome. These results are
      similar to those reported in the United States and Canada, except for the result
      that Japanese patients with BPD are more likely to live with their original
      family at follow-up than American patients.

PMID- 16905411
TI  - Clinical implications of our advancing knowledge of colorectal cancer genetics:
      inherited syndromes, prognosis, prevention, screening and therapeutics.
AB  - Recent genetic advances in our knowledge of colorectal cancer genetics are
      beginning to pay translational dividends in the management of this common
      clinical problem. We are now able to accurately screen and counsel individuals at
      risk of rare inherited cancer syndromes. We have recently introduced two of what
      are sure to be numerous biologic-based therapies, and have shown that colorectal
      neoplasia risk can be modestly reduced by various chemopreventative agents.
      Finally, our advancing knowledge has led to significant inroads into
      understanding what genetic alterations define prognosis and predict response to
      specific chemotherapeutic agents, and we are beginning to explore the utility of
      this knowledge in mass genetic-based clinical screening efforts. Enthusiasm must
      be tempered, however, by the extraordinary cost that often accompanies relatively
      modest gains. Finally, although genetic-based therapy often receives the greatest
      attention, molecular genetics, will likely have the greatest cost-effective
      impact in primary prevention and early diagnosis.

PMID- 16905412
TI  - An update on imaging of colorectal cancer.
AB  - Screening of asymptomatic average-risk patients for presence of colon cancer and
      early detection in precursor stages is of great interest to general population.
      Comprehensive evaluation of symptomatic or high-risk patients represents another
      important clinical focus. Available techniques for total colon imaging, rectal
      cancer staging and the role of positron emission tomography are discussed.

PMID- 16905413
TI  - Advances in gastrointestinal endoscopic techniques.
AB  - An increasing number of techniques for endoscopic diagnosis and treatment is
      being described. Endoscopic surgeons should be familiar with these techniques.
      Although many of the diagnostic techniques, other than marking, do not have
      widespread clinical application, the therapeutic techniques that were described
      in this article are being used successfully in increasing numbers of
      appropriately selected patients. Additional experience and technologic advances
      will refine the endoscopic therapy that is available to patients with colorectal
      diseases.

PMID- 16905414
TI  - Laparoscopic colon surgery: past, present and future.
AB  - Since its first described case in 1991, laparoscopic colon surgery has lagged
      behind minimally invasive surgical methods for solid intra-abdominal organs in
      terms of acceptability, dissemination, and ease of learning. In colon cancer,
      initial concerns over port site metastases and adequacy of oncologic resection
      have considerably dampened early enthusiasm for this procedure. Only recently,
      with the publication of several large, randomized controlled trials, has the
      incidence of port site metastases been shown to be equivalent to that of open
      resection. Laparoscopic surgery for colon cancer has also been demonstrated to be
      at least equivalent to traditional laparotomy in terms of adequacy of oncologic
      resection, disease recurrence, and long-term survival. In addition, numerous
      reports have validated short-term benefits following laparoscopic resection for
      cancer, including shorter hospital stay, shorter time to recovery of bowel
      function, and decreased analgesic requirements, as well as other postoperative
      variables. In benign colonic disease, much less high-quality literature exists
      supporting the use of laparoscopic methods. Two recent randomized controlled
      trials have demonstrated some short-term benefits to laparoscopic ileocolic
      resection for CD, in addition to evident cosmetic advantages. On the other hand,
      the current evidence on laparoscopic surgery for UC does not support its routine
      use among nonexpert surgeons outside of specialized centers. Laparoscopic colonic
      resection for diverticular disease appears to provide several short-term
      benefits, although these advantages may not translate to cases of complicated
      diverticulitis. Despite the increasing acceptability of minimally invasive
      methods for the management of benign and malignant colonic pathologies,
      laparoscopic colon resection remains a prohibitively difficult technique to
      master. Numerous technological innovations have been introduced onto the market
      in an effort to decrease the steep learning curve associated with laparoscopic
      colon surgery. Good evidence exists supporting the use of second-generation,
      sleeveless, hand-assist devices in this context. Similarly, new hemostatic
      devices such as the ultrasonic scalpel and the electrothermal bipolar vessel
      sealer may be particularly helpful for extensive colonic mobilizations, in which
      several vascular pedicles must be taken. The precise role of these hemostatic
      technologies has yet to be established, particularly in comparison with stapling
      devices and significantly cheaper laparoscopic clips. Finally, recent advances in
      camera systems are promising to improve the ease with which difficult colonic
      dissections can be performed.

PMID- 16905415
TI  - Laparoscopic rectal surgery: rectal cancer, pelvic pouch surgery, and rectal
      prolapse.
AB  - With the increasing popularity of minimally invasive approaches to surgery,
      laparoscopic techniques are being applied increasingly to more complex
      procedures. Surgeons who are interested in gaining skill and confidence with the
      techniques of rectal mobilization and resection initially should consider
      attempting procedures for benign disease. Patients who have rectal prolapse, who
      often have wide, accommodating pelvic anatomy, are the logical choice with whom
      to begin the laparoscopic rectal experience. Laparoscopic restorative
      proctocolectomy is more technically challenging. Laparoscopic proctectomy for
      rectal cancer probably should remain in the hands of well-trained, high-volume,
      experienced surgeons who have built a dedicated team for treatment of these
      patients, and who track their outcomes prospectively.

PMID- 16905416
TI  - Transanal endoscopic microsurgery.
AB  - TEM has been used effectively to treat large rectal polyps and early rectal
      malignancy for more than 20 years in Europe. Until recently, only a few
      specialized centers offered TEM in the United States, where it is now gaining
      popularity. Many hospitals have purchased equipment and are offering TEM;
      however, the equipment is expensive and the learning curve is steep. Therefore,
      it is essential that anyone performing TEM have an adequate number of cases to
      develop and maintain expertise in this technique. That being said, TEM remains
      unique when compared with laparoscopy and other minimally invasive techniques
      that incorporate less invasive methods of performing old operations. TEM allows
      surgeons to perform operations that were impossible before the development and
      acceptance of this technique.

PMID- 16905417
TI  - Robotics in colorectal surgery: telemonitoring and telerobotics.
AB  - Surgery has just passed through the laparoscopic surgery revolution, with
      validation of the advantages for the patient evaluated painstakingly; however,
      laparoscopy is a transition phase to fully information-based surgery, which only
      can be accomplished when hand motions are converted to information through
      robotic surgery systems. The main advantage is using such systems to integrate
      the entire surgical process. The components that will allow such a transition
      exist in other industries that use robotics, so it is more a matter of applying
      these engineering principles to surgery, rather than inventing new technologies.
      Robotics cannot only improve the performance of surgery, but is providing access
      to surgical expertise in remote and underserved areas through telementoring,
      teleconsultation, and telesurgery. Colorectal surgeons should seize the
      opportunity to begin to use surgical robotic systems in those niche areas and
      procedures that have proven to be of significant benefit to the patient and are
      cost-effective. Over time, with the development of even more advanced systems it
      will become more advantageous to use robotics on a routine basis.

PMID- 16905418
TI  - New techniques in the treatment of common perianal diseases: stapled
      hemorrhoidopexy, botulinum toxin, and fibrin sealant.
AB  - There have been several recent advances in the treatment of common perianal
      diseases. Stapled hemorrhoidopexy is a procedure of hemorrhoidal fixation,
      combining the benefits of rubber band ligation into an operative technique. The
      treatment of anal fissure has typically relied upon internal sphincterotomy;
      however, it carries a risk of incontinence. The injection of botulinum toxin
      represents a new form of sphincter relaxation, without division of any sphincter
      muscle; morbidity is minimal and results are promising. For the treatment of
      fistula in a fistulotomy remains the gold standard, however, it carries
      significant risk of incontinence. Use of fibrin sealant to treat fistulae has
      been met with variable success. It offers sealing of the tract, and then provides
      scaffolding for native tissue ingrowth.

PMID- 16905420
TI  - Advanced laparoscopic skills acquisition: the case of laparoscopic colorectal
      surgery.
AB  - Acquisition of advanced technical skills requires commitment, time, patience, and
      discipline (eg, the 10-year rule). Dabbling is not a recipe for success. Despite
      the value of all other teaching methods, guided practice with feedback is
      essential to develop the high level of visuospatial perceptual ability
      (observation and performance with feedback) that is necessary for advanced MIS.
      The necessary ingredients to skill acquisition for advanced MIS procedures
      (laparoscopic colorectal surgery) for a practicing surgeon include introduction
      through short courses, access to skill stations, and access to preceptorship or
      mini-sabbatical. For residents in training, there is no better alternative than
      an MIS fellowship. In an ideal world where there are enough trainers, the
      residency environment should provide this training. Comprehensive strategies of
      knowledge transfer for practicing surgeons should be designed with the input of
      experts in knowledge transfer.

PMID- 16905419
TI  - Novel approaches in the treatment of fecal incontinence.
AB  - The availability of novel techniques to treat end-stage FI gives hope for a
      better quality of life in patients who were traditionally treated by a permanent
      stoma. The diversity of causes of FI and the different modes of action of the
      various treatment modalities mandate a tailored, individualized approach in each
      case. A meticulous preoperative evaluation process is imperative in the course of
      the decision-making of which procedure to perform, with full awareness that a
      stoma still may be the best option for some patients who have end-stage FI.

PMID- 16905421
TI  - Evolving techniques in the treatment of liver colorectal metastases: role of
      laparoscopy, radiofrequency ablation, microwave coagulation, hepatic arterial
      chemotherapy, indications and contraindications for resection, role of
      transplantation, and timing of chemotherapy.
AB  - The management of patients who have hepatic metastases from CRC has become
      increasingly complex as the number of modalities that is available to treat these
      tumors has increased. Surgical resection remains the mainstay of treatment, when
      possible, and may become an option in an increasing proportion of patients that
      has advanced disease and previously were considered unresectable when treated
      with a combination of neoadjuvant systemic or hepatic arterial chemotherapy. The
      role of microwave coagulation and RFA can be considered only complementary to
      surgical resection at this point, but they may represent the best option in
      highly selected patients, such as those who are at high risk for extrahepatic
      recurrence or who are poor surgical candidates.

PMID- 16905422
TI  - New agents, combinations, and opportunities in the treatment of advanced and
      early-stage colon cancer.
AB  - There has been a dramatic improvement in outcomes for patients who have colon
      cancer over recent years. These improvements have come about largely because of
      the availability of new chemotherapy agents (irinotecan, oxaliplatin and
      capecitabine) and new biologic agents (bevacizumab and cetuximab). Large, well
      designed clinical trials have resulted in the routine use of all of these agents
      in the treatment of patients who have metastatic disease, and this has led to
      improved survival for these patients. In earlier stage disease, oxaliplatin/5-FU
      based chemotherapy has become a new standard of adjuvant therapy for many
      patients. Clinical research efforts are investigating the use of biologic agents
      along with chemotherapy for adjuvant treatment; it is hoped that this will
      translate into a greater cure rate for these patients.

PMID- 16905423
TI  - New therapies for the treatment of inflammatory bowel disease.
AB  - Medical therapy of IBD has made remarkable progress in recent years, driven
      forward by new knowledge about mechanisms of disease and advances in
      biotechnology. As we continue to learn about how best to use the agents currently
      in our hands, the addition of new drugs will further improve outcomes, and will
      bring new insights into the fundamental causes of these diseases.

PMID- 16905424
TI  - Palliating patients who have unresectable colorectal cancer: creating the right
      framework and salient symptom management.
AB  - The last phases of colorectal malignant illness may be the most challenging and
      saddening for all involved, but they offer opportunities to become the most
      rewarding. This transformation of hopelessness to fulfillment requires a
      willingness by surgeon, patient, and patient's family to trust one another to
      realistically set goals of care, stick together, and not let the treatment of the
      disease become a surrogate for treating the suffering that characterizes grave
      illness.

PMID- 16905425
TI  - The fishery for Iceland scallop (Chlamys islandica) in the Northeast Atlantic.
AB  - This review focuses on the history and management of the Iceland scallop fishery
      in Iceland, Greenland and Norway (including the Svalbard archipelago and the
      islands of Bjornoya and Jan Mayen), with information on research into each stock.
      The start of the fishery in all these regions followed the discovery of virgin
      scallop beds made up of old, large specimens in very high densities. Despite the
      apparent similarity of original conditions, the fishery has followed very
      different trends in each region, with drastic declines in Iceland, Svalbard and
      Jan Mayen. The general biology of the Iceland scallop is summarised and compared
      with the biology of other North Atlantic species of pectinids. The Icelandic
      fishery dates from 1969. There was a steady decrease in catch from 1985, when
      >16,000 tonnes were caught. By 2004 the stock had declined to 35% of its average
      size during the period 1993-2000 and a zero quota was advised. This decline is
      thought to have resulted from overexploitation, combined with a protozoan
      infestation and increasing sea bottom temperature. Scallop dredging commenced in
      west Greenland in 1983. The stock is not very large, but fishing was driven by
      social factors. Catches ranged from 400 to 1,900 tonnes during the period 1988
      1992 and from 1,200 to 2,600 tonnes since 1995. There are indications that each
      scallop bed is extensively dredged before the fleet moves on to new areas, but
      nevertheless catches have been rather stable over the past decade. The scallop
      stocks in Svalbard, Bjornoya and Jan Mayen were depleted in three fishing seasons
      between 1985-1987, when up to 45,000 tonnes of scallops were dredged in a single
      season. Following a survey carried out in 1991, Bjornoya was open to the fishery
      with a maximum quota of 2,000 tonnes, but the stock off Svalbard was found to be
      not large enough to sustain a fishery.

PMID- 16905426
TI  - Are larvae of demersal fishes plankton or nekton?
AB  - A pelagic larval stage is found in nearly all demersal marine teleost fishes, and
      it is during this pelagic stage that the geographic scale of dispersal is
      determined. Marine biologists have long made a simplifying assumption that
      behaviour of larvae--with the possible exception of vertical distribution--has
      negligible influence on larval dispersal. Because advection by currents can take
      place over huge scales during a pelagic larval stage that typically lasts for
      several days to several weeks, this simplifying assumption leads to the
      conclusion that populations of marine demersal fishes operate over, and are
      connected over, similar huge scales. This conclusion has major implications for
      our perception of how marine fish populations operate and for our management of
      them. Recent (and some older) behavioural research-reviewed here-reveals that for
      a substantial portion of the pelagic larval stage of perciform fishes, the
      simplifying assumption is invalid. Near settlement, and for a considerable
      portion of the pelagic stage prior to that, larvae of many fish species are
      capable of swimming at speeds faster than mean ambient currents over long
      periods, travelling tens of kilometres. Only the smallest larvae of perciform
      fishes swim in an energetically costly viscous hydrodynamic environment (i.e.,
      low Reynolds number). Vertical distribution is under strong behavioural control
      from the time of hatching, if not before, and can have a decisive, if indirect,
      influence on dispersal trajectories. Larvae of some species avoid currents by
      occupying the epibenthic boundary layer. Larvae are able to swim directionally in
      the pelagic environment, with some species apparently orientating relative to the
      sun and others to settlement sites. These abilities develop relatively early, and
      ontogenetic changes in orientation are seemingly common. Larvae of some species
      can use sound to navigate, and others can use odour to find settlement habitat,
      at least over small scales. Other senses may also be important to orientation.
      Larvae are highly aware of their environment and of potential predators, and some
      school during the pelagic larval stage. Larvae are selective about where they
      settle at both meso and micro scales, and settlement is strongly influenced by
      interactions with resident fishes. Most of these behaviours are flexible; for
      example, swimming speeds and depth may vary among locations, and speed may vary
      with swimming direction. In direct tests, these behaviours result in dispersal
      different from that predicted by currents alone. Work with both tropical and
      temperate species shows that these behaviours begin to be significant relatively
      early in larval development, but much more needs to be learned about the ontogeny
      of behaviour and sensory abilities in larvae of marine fishes. As a preliminary
      rule of thumb, behaviour must be taken into account in considerations of
      dispersal after the preflexion stage, and vertical distribution behaviour can
      influence dispersal from hatching. Larvae of perciform fishes are close to being
      planktonic at the start of the pelagic period and are clearly nektonic at its
      end, and for a substantial period prior to that. All these things differ among
      species. Larvae of clupeiform, gadiform and pleuronectiform fishes may be less
      capable behaviourally than perciform fishes, but this remains to be confirmed.
      Clearly, these behaviours, along with hydrography, must be included in modelling
      dispersal and retention and may provide explanations for recent demonstrations of
      self-recruitment in marine fish populations. Current work is directed at
      understanding the ontogeny of the gradual transition from planktonic to nektonic
      behaviour. Although it is clear that larvae of perciform fishes have the ability
      to strongly influence their dispersal trajectories, it is less clear whether or
      how these abilities are applied.

PMID- 16905427
TI  - Sound as an orientation cue for the pelagic larvae of reef fishes and decapod
      crustaceans.
AB  - The pelagic life history phase of reef fishes and decapod crustaceans is complex,
      and the evolutionary drivers and ecological consequences of this life history
      strategy remain largely speculative. There is no doubt, however, that this life
      history phase is very significant in the demographics of reef populations. Here,
      we initially discuss the ecology and evolution of the pelagic life histories as a
      context to our review of the role of acoustics in the latter part of the pelagic
      phase as the larvae transit back onto a reef. Evidence is reviewed showing that
      larvae are actively involved in this transition. They are capable swimmers and
      can locate reefs from hundreds of metres if not kilometres away. Evidence also
      shows that sound is available as an orientation cue, and that fishes and
      crustaceans hear sound and orient to sound in a manner that is consistent with
      their use of sound to guide settlement onto reefs. Comparing particle motion
      sound strengths in the field (8 x 10(-11) m at 5 km from a reef) with the
      measured behavioural and electrophysiological threshold of fishes of (3 x 10(-11)
      m and 10 x 10(-11), respectively) provides evidence that sound may be a useful
      orientation cue at a range of kilometres rather than hundreds of metres. These
      threshold levels are for adult fishes and we conclude that better data are needed
      for larval fishes and crustaceans at the time of settlement. Measurements of
      field strengths in the region of reefs and threshold levels are suitable for
      showing that sound could be used; however, field experiments are the only
      effective tool to demonstrate the actual use of underwater sound for orientation
      purposes. A diverse series of field experiments including light-trap catches
      enhanced by replayed reef sound, in situ observations of behaviour and sound
      enhanced settlement rate on patch reefs collectively provide a compelling case
      that sound is used as an orientation and settlement cue for these late larval
      stages.

PMID- 16905428
TI  - Crustacea in Arctic and Antarctic sea ice: distribution, diet and life history
      strategies.
AB  - This review concerns crustaceans that associate with sea ice. Particular emphasis
      is placed on comparing and contrasting the Arctic and Antarctic sea ice habitats,
      and the subsequent influence of these environments on the life history strategies
      of the crustacean fauna. Sea ice is the dominant feature of both polar marine
      ecosystems, playing a central role in physical processes and providing an
      essential habitat for organisms ranging in size from viruses to whales.
      Similarities between the Arctic and Antarctic marine ecosystems include variable
      cover of sea ice over an annual cycle, a light regimen that can extend from
      months of total darkness to months of continuous light and a pronounced
      seasonality in primary production. Although there are many similarities, there
      are also major differences between the two regions: The Antarctic experiences
      greater seasonal change in its sea ice extent, much of the ice is over very deep
      water and more than 80% breaks out each year. In contrast, Arctic sea ice often
      covers comparatively shallow water, doubles in its extent on an annual cycle and
      the ice may persist for several decades. Crustaceans, particularly copepods and
      amphipods, are abundant in the sea ice zone at both poles, either living within
      the brine channel system of the ice-crystal matrix or inhabiting the ice-water
      interface. Many species associate with ice for only a part of their life cycle,
      while others appear entirely dependent upon it for reproduction and development.
      Although similarities exist between the two faunas, many differences are
      emerging. Most notable are the much higher abundance and biomass of Antarctic
      copepods, the dominance of the Antarctic sea ice copepod fauna by calanoids, the
      high euphausiid biomass in Southern Ocean waters and the lack of any species that
      appear fully dependent on the ice. In the Arctic, the ice-associated fauna is
      dominated by amphipods. Calanoid copepods are not tightly associated with the
      ice, while harpacticoids and cyclopoids are abundant. Euphausiids are nearly
      absent from the high Arctic. Life history strategies are variable, although
      reproductive cycles and life spans are generally longer than those for temperate
      congeners. Species at both poles tend to be opportunistic feeders and periods of
      diapause or other reductions in metabolic expenditure are not uncommon.

PMID- 16905430
TI  - Methaemoglobinaemia secondary to the ingestion of sodium nitrite in mistake for
      common salt.

PMID- 16905433
TI  - Dissemination patterns of pilocytic astrocytoma.
AB  - Two patients with multifocal pilocytic astrocytoma diagnosed by magnetic
      resonance imaging (MRI) and confirmed by histopathological examination are
      reported. They presented distinct sites and mechanisms of metastasis: to distant
      ventricles through the cerebral spinal fluid (CSF) in patient 1 and to
      contralateral parenchyma, possibly through white matter tracts, in patient 2, a
      pathway not so far reported in pilocytic astrocytoma. Early detection of
      multifocal pilocytic astrocytoma by MRI may change treatment strategies and
      improve prognosis.

PMID- 16905434
TI  - Spontaneous migration of a bullet into the brain.
AB  - We report the case of a 20-year-old man with a gunshot injury as an example of
      spontaneous migration of a metallic foreign body within the brain. Computed
      tomography (CT) showed the bullet in the left temporoparietal region. At 10 days
      follow-up, CT revealed that the bullet had migrated posteriorly, due to the
      effect of gravity, lodging in the occipital lobe. Although there are a few
      literature reports of spontaneous migration of a bullet within the brain, this
      case was unique as the patient was fully conscious without any neurological
      deficit.

PMID- 16905435
TI  - Red blood cell indices in children with idiopathic epilepsy: A case-control
      study.

PMID- 16905436
TI  - Levofloxacin-induced delirium: Diagnostic considerations.

PMID- 16905437
TI  - Perspectives from the International Conference on Communication in Healthcare:
      Chicago 2005.

PMID- 16905438
TI  - Alcohol consumption patterns among pregnant women in the Moscow region of the
      Russian Federation.
AB  - Data regarding the prevalence and patterns of alcohol consumption among pregnant
      women in the Russian Federation is lacking. As part of a longitudinal pregnancy
      outcome study being conducted in the Moscow Region of Russia, in the 5-month
      period from January through May 2005, pregnant women in four prenatal care
      facilities were screened for self-reported alcohol consumption in the month
      around the time of conception and in the most recent month of pregnancy. Among
      the 413 respondents, 347 (85.0%) reported some alcohol consumption during one of
      the two time periods, and 193 (51.9%) of these drinking women reported some
      alcohol use in the most recent month. Of particular concern was the pattern of
      drinking, with 75 (20.2%) of drinking women reporting at least one episode of
      five or more drinks around the time of conception, and 153 (41.1%) of drinking
      women reporting at least one episode of three or four drinks during that same
      time period. Furthermore, this same pattern of heavier episodic drinking was
      reported by 18 (4.8%) and 39 (10.5%) of drinking women, respectively, in the most
      recent month in pregnancy before the screening interview. These data indicate
      that pregnant women in these areas of the Moscow Region present an important
      opportunity for education and intervention for alcohol-related birth outcomes.

PMID- 16905439
TI  - The influence of ethanol on blood flow velocity in major cerebral vessels. A
      prospective and controlled study.
AB  - Cerebral vasospasm secondary to subarachnoid hemorrhage leads to increased
      cerebrovascular resistance and may cause ischemia in the affected vascular
      territories. The currently available therapeutic options for treating vasospasm
      are limited. The effect of ethanol at a concentration of 0.75 g/kg body weight on
      blood flow velocity in the major cerebral arteries was studied. In 31 healthy
      persons, the major extra- and intracranial cerebral vessels were examined by
      Doppler ultrasonography before and following oral ingestion of 0.75 g/kg body
      weight of ethanol. An additional 20 healthy subjects served as a control group.
      Ethanol in the applied concentration significantly increased the systolic,
      diastolic, and mean blood flow velocities and significantly decreased the
      pulsatility indices in the middle cerebral artery (MCA). It may reduce vascular
      resistance and may increase cerebral blood flow in the area supplied by the MCA
      in healthy persons.

PMID- 16905440
TI  - Alcohol and the risk of colon and rectal cancer with mutations in the K-ras gene.
AB  - The first metabolite of alcohol, acetaldehyde, may trigger replication errors and
      mutations in DNA, which may predispose to developing colorectal cancer (CRC). In
      a prospective study on colon and rectal cancer, we investigated the following
      hypotheses: alcohol consumption is associated with an increased risk of mutations
      in the K-ras oncogene, and beer consumption is associated with an increased risk
      of G-->A mutations in this gene. Therefore, we studied the associations between
      consumption of alcohol and alcoholic beverages and the risk of CRC without and
      with specific K-ras gene mutations. In 1986, 120,852 men and women, aged 55-69
      years, completed a questionnaire on risk factors for cancer. The case-cohort
      approach was used for data processing and analyses. After 7.3 years of follow-up,
      excluding the first 2.3 years, complete data from 4,076 subcohort members, 428
      colon and 150 rectal cancer patients, were available for data analyses. Incidence
      rate ratios (RRs) and corresponding 95% confidence intervals (95% CIs) were
      estimated using Cox proportional hazards models. Compared to abstaining, a total
      alcohol consumption of 30.0 g/day and more was associated with the risk of colon
      and rectal cancer with and without a K-ras mutation in both men and women.
      Independent from alcohol intake, liquor consumption when compared to nonliquor
      consumption was associated with an increased risk of rectal cancer with a wild
      type K-ras in men (RR: 2.25, 95% CI: 1.0-5.0). Beer consumption was not clearly
      associated with the risk of colon and rectal tumors harboring G-->A mutations in
      the K-ras gene in men. This association could not be assessed in women because of
      sparse beer consumption. In conclusion, alcohol does not seem to be involved in
      predisposing to CRC through mutations in the K-ras gene, and specifically beer
      consumption is not associated with colon and rectal tumors harboring a G-->A
      mutation.

PMID- 16905441
TI  - Effects of multiple alcohol deprivations on operant ethanol self-administration
      by high-alcohol-drinking replicate rat lines.
AB  - Previously, we reported that the expression of an alcohol deprivation effect
      (ADE) under 24-h free-choice alcohol-drinking access in high-alcohol-drinking
      (HAD) replicate lines of rats is dependent upon repeated cycles of alcohol access
      and forced abstinence. In the present study, operant techniques (including
      progressive ratio measures) were used to examine the effects of initial
      deprivation length and number of deprivation cycles on the magnitude and duration
      of the ADE in HAD rats to test the hypothesis that repeated deprivations increase
      the reinforcing effects of ethanol. Adult male HAD-1 and HAD-2 rats were trained
      in two-lever operant chambers to concurrently self-administer 15% ethanol (v/v)
      on a fixed-ratio (FR)-5 schedule and water on an FR-1 schedule of reinforcement
      in daily 1-h sessions. Following 10 weeks of daily 1-h sessions, the HAD-1 and
      HAD-2 rats were randomly assigned to one of four groups (n=6-8/group/line):
      nondeprived, or deprived of alcohol for 2, 5, or 8 weeks. Following this initial
      period, the deprived groups were given 15% ethanol again in the operant chambers
      for a 2-week period, following which they were deprived again for 2 weeks (all
      three deprived groups). Following the fifth deprivation, the rats underwent a
      progressive ratio test to determine the breakpoints for the nondeprived and
      deprived groups. The expression of an ADE under operant conditions in HAD rats
      was dependent upon exposure to repeated cycles of ethanol access and abstinence.
      Additionally, repeated deprivations increased both the magnitude and the duration
      of the ADE as indicated by increased responding on the ethanol lever for more
      sessions. Breakpoint values for the deprived groups were 1.5-fold and twofold
      higher than the value for the nondeprived group for the HAD-1 and HAD-2 rats,
      respectively. The results suggest that repeated alcohol deprivations increased
      the expression of an ADE and the reinforcing effects of ethanol in both HAD
      replicate lines of rats, and these effects were more pronounced in the HAD-2 line
      than the HAD-1 line.

PMID- 16905442
TI  - Decreased reward during acute alcohol withdrawal in rats selectively bred for low
      alcohol drinking.
AB  - We have previously hypothesized that increased sensitivity to the dysphoric-like
      or aversive effects of alcohol withdrawal following an initial exposure to
      alcohol might be associated with a genetic propensity to avoid alcohol. A
      decrease in brain reward function, as measured by an elevation in intracranial
      self-stimulation (ICSS) reward threshold, is one of the few methods available to
      model dysphoric-like or aversive effects of drug withdrawal in rats. We compared
      brain reward function during withdrawal following an initial exposure to alcohol
      in alcohol-naive rats selectively bred for high (HAD1 line) versus low (LAD1
      line) voluntary alcohol consumption. Male HAD1 (n=5) and LAD1 (n=6) rats were
      implanted with unilateral electrodes in the medial forebrain bundle and trained
      to bar press for delivery of a 100 microA current that varied in frequency from
      45 to 200 Hz. Responding for ICSS was generally stable within subjects across
      multiple experimental sessions on a given day and across several consecutive days
      prior to alcohol or water administration. ICSS responding was assessed in both
      rat lines prior to and at 12, 14, 16, 18, 20, and 24 h following a single
      intragastric infusion of alcohol (4.0 g/kg body weight) or water. Rats of the
      LAD1 line, but not those of the HAD1 line, exhibited a decrease in brain reward
      function as evidenced by a decrease in bar-press responding for ICSS and an
      increase in ICSS stimulation threshold during alcohol withdrawal. The results
      suggest that rats selectively bred for low alcohol drinking may experience
      dysphoric-like effects during withdrawal from an initial exposure to alcohol,
      while rats selectively bred for high alcohol drinking may not.

PMID- 16905443
TI  - Chronic daily ethanol and withdrawal: 6. Effects on rat sympathoadrenal activity
      during "abstinence".
AB  - We have reported that repetitive daily ethanol consumption increased anxiety-like
      behavior in rats 4 weeks after ethanol consumption had ceased, consistent with
      the persistently increased anxiety exhibited by abstinent alcoholics. Increased
      anxiety is associated with sympathoadrenal activation, so we have now also
      investigated ethanol-induced persistent changes in basal and stress-induced
      plasma epinephrine (E) and norepinephrine (NE) levels. Male Sprague-Dawley rats
      received liquid diet containing ethanol versus pair-fed isocaloric control liquid
      diet for 9 weeks. After 5 weeks' subsequent "abstinence" (i.e., no ethanol in the
      diet), the control rats exhibited low basal plasma E and NE, which were both
      increased by 150-300% within 5 min after transfer to a novel cage in a novel
      room, returning toward basal levels within 15 min. "Abstinent" ethanol-treated
      rats exhibited elevated basal E levels (195% of controls, P<.05), which were not
      significantly altered by transfer to novel environment; basal NE levels tended
      (P<.07) to be elevated and likewise were not altered by novel environment. These
      results suggest that daily ethanol consumption can induce persistent increases in
      sympathoadrenal activation during subsequent "abstinence," which are relatively
      refractory to further stimulation.

PMID- 16905444
TI  - Reduced ability of ethanol drinkers for social communication in honeybees (Apis
      mellifera carnica Poll.).
AB  - Foraging behavior was evaluated in honeybees trained to fly to a feeder
      containing sucrose only, 1% ethanol, 5% ethanol, or 10% ethanol. The results
      indicated that exposure to ethanol disrupted several types of honeybee social
      behavior within the hive. Consumption of ethanol at the feeding site reduced
      waggle dance activity in foraging bees and increased occurrence of tremble dance,
      food exchange, and self-cleaning behavior. These ethanol-induced changes in
      behavior may reflect effects on the central nervous system similar to the
      previously observed effects of food poisoning with sublethal doses of
      insecticides.

PMID- 16905445
TI  - Binge alcohol exposure during all three trimesters alters bone strength and
      growth in fetal sheep.
AB  - Women who drink while pregnant are at a high risk of giving birth to children
      with neurodevelopmental disorders. Heavy consumption of alcohol during pregnancy
      is also known to be deleterious to fetal bone growth in both humans and
      laboratory animals. However, nothing is known regarding the effect of maternal
      moderate and heavy alcohol binging on fetal and maternal bone strength. The
      purpose of this study was to determine the effects of moderate and heavy alcohol
      binging throughout gestation on fetal and maternal bone growth and strength. The
      study was conducted using an ovine model system. The large body mass of the ovine
      fetus, the longer gestation that is more similar to that of humans, and the fact
      that all three trimester equivalents occur in utero, make the sheep an excellent
      model for studying Fetal Alcohol Spectrum Disorder. Suffolk ewes were mated and,
      beginning on gestational day 4, received intravenous infusions over 1 h on 3
      consecutive days per week followed by 4 days without treatment concluding on day
      132 of pregnancy. Pregnant ewes were divided into four groups: two alcohol
      treatment groups (0.75 and 1.75 g/kg of body weight), one pair-fed saline control
      group, and an untreated normal control group. The fetuses were harvested on
      gestational day 133. Maternal and fetal femoral and tibial dimensions were
      measured and the maximum strength (MPa) carried by the bone tissue was determined
      using a three-point bending procedure. Maternal bones were not different among
      groups. The higher alcohol dose resulted in reduced fetal femoral bone strength,
      whereas the tibial bone strength was lower when compared with the normal control
      subjects. In contrast, the lower alcohol dose increased fetal femoral strength
      compared to the normal control subjects. The alcohol-exposed fetal bones also
      tended to exhibit reduced lengths. We conclude that binge alcohol exposure
      throughout gestation resulted in dose-dependent differences in the maximum stress
      absorbed by the fetal bones.

PMID- 16905447
TI  - Mantle fields in the era of dynamic multileaf collimation: field shaping and
      electronic tissue compensation.
AB  - Mantle field radiotherapy for Hodgkin's disease is complicated by significant
      dose gradient (up to 10-20%) across the large fields required. Many different
      strategies of tissue compensation have been investigated, including custom
      physical compensators to provide better dose distributions. We present a method
      using dynamic multileaf collimator (dMLC) fluence modulation to simultaneously
      shape the treatment field and give homogeneous dose at depth throughout the
      classic mantle field. Five patients were treated for early-stage Hodgkin's
      disease with a conventional anterior-posterior-posterior-anterior (AP-PA) mantle
      field. The patients were planned using the Varian Eclipse treatment planning
      system, version 6.1.3, and treated on a Varian 2300CD. An AP-PA dynamic MLC beam
      shaped and dose-compensated plan was created for each, and compared with the
      conventional blocked plan. Nine dose points were calculated at midplane in each
      plan. Chamber measurements were taken to confirm accurate dMLC delivery of the
      planned doses. The mean dose per fraction, relative to a central axis dose of 1.8
      Gy, was increased in the conventional plans compared with the dMLC plans in the
      right (R) neck, left (L) neck, R supraclavicular, L supraclavicular, and L
      axillary points. The mediastinum tended to be underdosed relative to central
      axis, with the mid-mediastinal and lower mediastinal points showing improved
      coverage with the dMLC plans. Measurements showed excellent agreement between
      planned doses and delivered doses, with less than 2% in-field variation. Dynamic
      MLC fluence modulation was used to effectively deliver a mantle field that is
      both shape- and electronically-dose-compensated with sliding window MLC.
      Homogeneity was significantly improved throughout the treatment field, and
      measurements confirmed accurate dose delivery using this technique.

PMID- 16905448
TI  - Optimum parameters of TLD100 powder used for radiotherapy beams calibration
      check.
AB  - External audit of the absorbed dose determination from radiotherapy machines is
      performed using Lithium fluoride (LiF) TLD-100. Optimal parameters needed to
      obtain highly accurate dosage from LiF powder was investigated, including the
      setup of the Harshaw 4000 reader. A linear correspondence between the
      thermoluminescent signal and the mass of the powder was observed, demonstrating
      that the dose can be evaluated with small samples of powder. The reproducibility
      of the thermoluminescence dosimeter (TLD) readings obtained with up to 10 samples
      from 1 capsule containing 160 mg of powder was around 1.5% (1 standard deviation
      [SD]). The time required for the manual evaluation of TLDs can be improved by 3
      readings without loss of accuracy. Better reproducibility is achieved if the
      capsules are evaluated 7 days after irradiation using a nitrogen flow of 300
      cc/min.

PMID- 16905449
TI  - Simultaneous-integrated boost intensity-modulated radiation therapy (SIB-IMRT) in
      the treatment of early-stage left-sided breast carcinoma.
AB  - We assessed the feasibility and impact of simultaneous-integrated boost intensity
      modulated radiation therapy (SIB-IMRT) in the treatment of left breast carcinoma
      and compared target coverage and normal tissue doses with SIB-IMRT and 3
      dimensional (3D) conformal RT using opposed tangential fields. For each of 10
      patients with early-stage left-sided invasive breast carcinoma, 5 plans were
      generated; the first 4 were 3D conformal opposed tangential fields-2 with wedges,
      2 with compensators and either photon or electron boost. A dose of 50.4 Gy in 28
      fractions was prescribed to the left breast and an additional 16 Gy in 8
      fractions to the lumpectomy bed. When compared to the tangential plans, SIB-IMRT
      maintained coverage (V(95%)) to the left breast and lumpectomy bed without
      significantly increasing the left breast maximum dose. SIB-IMRT was able to
      reduce the lung mean dose, maximum dose, and the V(20) by 55-104 cGy, 983-1298
      cGy (p < 0.001), and 3.7-4.4%, respectively. In addition, SIB-IMRT reduced the
      maximum heart dose by 1032-1173 cGy and contralateral breast dose was increased
      (although p = NS). The mean and maximum dose to the unspecified tissues was also
      significantly reduced by 81-88 cGy and 516-942 cGy, respectively. SIB-IMRT
      resulted in a significant improvement in target dose conformality by up to 67%.
      Our findings that SIB-IMRT could improve dose conformality, reduce total
      treatment times, and reduce some of the normal structure doses presents it as an
      alternative technique for adjuvant breast radiotherapy; however this needs to be
      studied further in the clinic setting.

PMID- 16905450
TI  - Evaluation of bladder dose in intensity-modulated radiation therapy of the
      prostate.
AB  - Day-to-day variation in bladder and rectal filling affects prostate location and
      positioning accuracy. Systems using ultrasonic localization or gold seed
      placement are most often used to help correct for these changes. At some
      institutions, patients are instructed to empty their rectum and fill their
      bladders prior to treatment in an attempt to standardize the prostate location,
      displace small bowel out of the radiation field, and move some of the bladder
      wall away from the high-dose area. Although instructed to come to treatment with
      a full bladder, it is presumed that there is variability in bladder filling each
      day of treatment, depending on the amount of fluids consumed and time to
      treatment. We have reviewed daily bladder volumes on a subset of 5 prostate
      patients, all of them prescribed to receive 7560 cGy in 42 fractions, and have
      evaluated the dosimetric consequences of bladder volume changes from full to two
      third or one-third filling. All of these patients' positions were verified daily
      with ultrasonic localization. Those measurements have been used to help analyze
      the actual treated bladder volumes for comparison with the treatment plan. We
      find that, in general, maximum filling only occurred on the initial
      simulation/image acquisition day and was typically smaller on all the following
      treatment days. Based on our dose-volume model, we estimate that average bladder
      daily doses were 8-50% higher than predicted by the initial intensity-modulation
      radiation therapy (IMRT) plan.

PMID- 16905451
TI  - Relative electron dosimetry using the Scanditronix-Wellhofer Beam Imaging System
      2G.
AB  - The Beam Imaging System 2G (BIS-2G) from Scanditronix-Wellhofer is a two
      dimensional (2D) charge-coupled device (CCD)-camera that measures the
      scintillation light produced by incident radiation. We examined the performance
      of the BIS-2G as a tool in quality control of patient boluses. In an attempt to
      simplify the production of the patient boluses, bolus edges were built as
      staircases and the dose distributions were measured and compared to the dose
      profiles below corresponding sloped bolus edges. Perspex plates covering half the
      irradiated field were used as generalized bolus edges. All BIS-2G measurements
      were performed using buildup of solid water while a diode measured corresponding
      dose profiles in a water phantom. Below the patient boluses, regions with doses <
      95% and > 107% of the prescribed dose were defined. Below the edge, the relative
      doses measured by the BIS-2G were generally within 3% in dose and 3 mm in
      position compared to the diode measurements. Close to the field edge below the
      bolus, the BIS-2G measurements were in some cases as much as 7% lower in dose
      than the diode measurements. The BIS-2G measurements revealed hotspots below the
      patient boluses covering 1-16% of the total irradiated area. The highest point
      dose measured below the patient boluses ranged from 105% to 125% of the
      prescribed dose. For all bolus thicknesses, each edge in the staircase bolus
      caused a fluctuation in dose and increased the maximum dose compared to the
      sloped edge. For several cases, the maximum dose increased with 13% in relative
      dose, e.g., from 103% to 116%. The BIS-2G was found to be a useful tool in
      quality control of patient boluses, revealing large hot spots in the treatment
      volume for several patients. Bolus edges built as staircases cause considerable
      dose fluctuations and increase the maximum dose, and can therefore not be
      recommended.

PMID- 16905452
TI  - Surface dose measurement using TLD powder extrapolation.
AB  - Surface/near-surface dose measurements in therapeutic x-ray beams are important
      in determining the dose to the dermal and epidermal skin layers during radiation
      treatment. Accurate determination of the surface dose is a difficult but
      important task for proper treatment of patients. A new method of measuring
      surface dose in phantom through extrapolation of readings from various
      thicknesses of thermoluminescent dosimeter (TLD) powder has been developed and
      investigated. A device was designed, built, and tested that provides TLD powder
      thickness variation to a minimum thickness of 0.125 mm. Variations of the
      technique have been evaluated to optimize precision with consideration of
      procedural ease. Results of this study indicate that dose measurements (relative
      to D(max)) in regions of steep dose gradient in the beam axis direction are
      possible with a precision (2 standard deviations [SDs]) as good as +/- 1.2% using
      the technique. The dosimeter was developed and evaluated using variation to the
      experimental method. A clinically practical procedure was determined, resulting
      in measured surface dose of 20.4 +/- 2% of the D(max) dose for a 10 x 10 cm(2),
      80-cm source-to-surface distance (SSD), Theratron 780 Cobalt-60 ((60)C) beam.
      Results obtained with TLD powder extrapolation compare favorably to other methods
      presented in the literature. The TLD powder extrapolation tool has been used
      clinically at the Northwestern Ontario Regional Cancer Centre (NWORCC) to measure
      surface dose effects under a number of conditions. Results from these
      measurements are reported. The method appears to be a simple and economical tool
      for surface dose measurement, particularly for facilities with TLD powder
      measurement capabilities.

PMID- 16905453
TI  - Choice of beam energy and dosimetric implications for radiation treatment in a
      subpopulation of women with large breasts in the United States and Japan.
AB  - Radiation complications are often related to the dose inhomogeneity (hot spot) in
      breast tissue treated with conservative therapy, especially for large patients.
      The effect of photon energy on radiation dose distribution is analyzed to provide
      guidelines for the selection of beam energy when tangential fields and limited
      slices are used to treat women with large breasts. Forty-eight patients with
      chest wall separation > 22 cm were selected for dosimetric analysis. We compared
      the maximum dose in the central axis (CAX) plane (2D) using 6-, 10-, and 18-MV
      photon beams in all patients and 3D data set for 16 patients. Correlation between
      hot spot dose (HSD), separation, breast cup size, breast volume, and body weight
      was derived with beam energy. Among the 48 patients in this study, HSD > 10% in
      the CAX plane was noted in 98%, 46%, and 4% of the population when 2D dosimetry
      was performed; however, with 3D study, it was in 50%, 19%, and 6% of the patients
      with 6-MV, 10-MV and 18-MV beams, respectively. The chest wall separation, body
      weight, and breast volume were correlated with the HSD in both the 2D and 3D
      plans. Patient's bra size was not correlated with the hot spot. The chest wall
      separation was found to be the most important parameter to correlate with hot
      spot in tangential breast treatment. Simple guidelines are provided for dose
      uniformity in breast with respect to chest wall separation, body weight, bra
      size, and breast volume with tangential field irradiations.

PMID- 16905454
TI  - Intensity-modulated radiotherapy (IMRT) for carcinoma of the maxillary sinus: a
      comparison of IMRT planning systems.
AB  - The treatment of maxillary sinus carcinoma with forward planning can be
      technically difficult when the neck also requires radiotherapy. This difficulty
      arises because of the need to spare the contralateral face while treating the
      bilateral neck. There is considerable potential for error in clinical setup and
      treatment delivery. We evaluated intensity-modulated radiotherapy (IMRT) as an
      improvement on forward planning, and compared several inverse planning IMRT
      platforms. A composite dose-volume histogram (DVH) was generated from a complex
      forward planned case. We compared the results with those generated by sliding
      window fixed field dynamic multileaf collimator (MLC) IMRT, using sets of
      coplanar beams. All setups included an anterior posterior (AP) beam, and 3-, 5-,
      7-, and 9-field configurations were evaluated. The dose prescription and
      objective function priorities were invariant. We also evaluated 2 commercial
      tomotherapy IMRT delivery platforms. DVH results from all of the IMRT approaches
      compared favorably with the forward plan. Results for the various inverse
      planning approaches varied considerably across platforms, despite an attempt to
      prescribe the therapy similarly. The improvement seen with the addition of beams
      in the fixed beam sliding window case was modest. IMRT is an effective means of
      delivering radiotherapy reliably in the complex setting of maxillary sinus
      carcinoma with neck irradiation. Differences in objective function definition and
      optimization algorithms can lead to unexpected differences in the final dose
      distribution, and our evaluation suggests that these factors are more significant
      than the beam arrangement or number of beams.

PMID- 16905455
TI  - Medical screening and the health of illegal immigrants in Australia.

PMID- 16905456
TI  - Risk of malaria among French adult travellers.
AB  - BACKGROUND: Imported malaria remains an important, but often unrecognised, health
      problem in Europe. Little information exists on the incidence of imported malaria
      with respect to exposure. This study aimed to estimate the incidence of malaria
      in a cohort of travellers with respect to protection measures. METHOD: In all
      13,017 participants enrolled in a French general population cohort (SU.VI.MAX
      cohort) and followed-up over 8 years were investigated. All participants received
      a retrospective questionnaire about travel to malaria-endemic countries relating
      to countries visited, duration of stay, use of protection measures and
      chemoprophylaxis. Malaria cases was confirmed from medical records. RESULTS: Data
      were obtained for 752 individuals who made 1,393 trips to malaria-endemic areas.
      This sample was predominantly middle-class and high-risk groups such as migrants
      were not represented. Mechanical protection was used in 589 trips (42.3%) and
      chemoprophylaxis in 1,017 trips (73.0%). This was appropriate for the zone in 615
      trips (44.0%) and adequate compliance was reported in the case of 497 trips
      (35.6%). Appropriate chemoprophylaxis and physical protection measures were used
      in 21.7% of the trips. Six laboratory-confirmed cases of imported malaria yielded
      an estimated incidence density of 148 cases/month of exposure/10,000 travellers.
      In five cases, appropriate protection measures had not been taken. CONCLUSION:
      Appropriate chemoprophylaxis and physical protection measures against malaria
      infection are used by less than one-quarter of a sample of predominantly middle
      class travellers from France to endemic areas. More intense education measures
      need to be implemented to reduce the risk of imported malaria.

PMID- 16905457
TI  - Retrospective: animal attacks and rabies exposures in Thai children.
AB  - Over 50% of animal bites and potential rabies exposures in Thailand are in
      children and they also have the more severe injuries due to inexperience, smaller
      size and less ability to fend off attacks. Potential rabies exposures and animal
      bites are common in Thailand. Majority of these are in children where the extent
      of the injuries is also much more severe. The bitten areas correlate to the age
      of the children and level of the bitten animal head. These are areas noted for a
      higher risk of infection with rabies virus and shorter incubation periods. The
      vast majority of bites are due to dogs (86%) of which 74.6% are stray or
      community-owned animals. The prevalence of dog bites shows no seasonal variation
      in adults but there are two peaks during school vacation period for children.
      Extensive educational efforts directed at the Thai public are responsible for the
      rapid presentation of victims for post-exposure treatment. The dramatic reduction
      of human rabies deaths in Thailand during the last decades was achieved largely
      by the provision of expensive WHO standard post-exposure treatment, utilizing
      modern tissue culture vaccines and immunoglobulins. Canine and feline rabies is
      nevertheless still endemic and not likely to be controlled or eliminated till
      sustainable humane methods of dog population control and comprehensive
      countrywide canine rabies vaccination become possible through government policy.

PMID- 16905458
TI  - Mansonella perstans causing symptomatic hypereosinophilia in a missionary family.
AB  - Mansonella perstans is rarely pathogenic. The rare reports of symptomatic cases,
      however, include severe complications. Three cases of symptomatic
      hypereosinophilia with multi-organ involvement are described in a missionary
      family returning from tropical Africa. Pathogenicity may be related to the
      induction of hypereosinophilia rather than direct host-parasite interactions.

PMID- 16905459
TI  - Stonefish envenomation--a lucky outcome.
AB  - Stonefish are one of the most intriguing examples of a perilous marine
      inhabitant. Equipped with a sophisticated defence mechanism, 13 dorsal spines
      armed with one of the most toxic fish venoms, against its natural foes, it lays
      perfectly camouflaged under the sand in shallow waters. Unsuspicious bypassers
      can be in for a deadly surprise as several fatalities, even after minor injuries,
      have been reported. We present an unlucky patient who sustained a single puncture
      wound causing her tremendous pain immediately. Surprisingly she did not develop
      complications after a considerable delay in receiving medical care. A review of
      the literature gives a brief account of pathophysiolology, complications and
      treatment.

PMID- 16905460
TI  - Acute pulmonary histoplasmosis from Ghana.
AB  - A male patient developed acute pulmonary histoplasmosis 2 weeks after bathing in
      the water falls of Wli, Ghana. Exposure to Histoplasma capsulatum was probably
      mediated through inhalation of an aerosol of water and guano from the large
      colony of fruit bats of the falls. More cases of acute pulmonary histoplasmosis
      can be expected.

PMID- 16905461
TI  - A case of exposure to Bancroftian filariasis in a traveller to Thailand.
AB  - A New Zealander travelling recreationally to Asia became exposed to Bancroftian
      filariasis. The traveller had presented incidentally with gastrointestinal
      illness. In addition to diarrhoea, the traveller's symptoms were non-specific and
      there was no eosinophilia, lymphoedema, lymphangitis, lymphadenitis, or pain. The
      immunochromatographic test for Wuchereria bancrofti was positive indicating that
      there was or had been an adult filarial worm. The illness resolved completely
      following treatment with ivermectin.

PMID- 16905462
TI  - Systemic armed oncolytic and immunologic therapy for cancer with JX-594, a
      targeted poxvirus expressing GM-CSF.
AB  - Targeted oncolytic viruses and immunostimulatory therapeutics are being developed
      as novel cancer treatment platforms. These approaches can be combined through the
      expression of immunostimulatory cytokines from targeted viruses, including
      adenoviruses and herpesviruses. Although intratumoral injection of such viruses
      has been associated with tumor growth inhibition, eradication of distant
      metastases was not reported. The major limitations for this approach to date have
      been (1) inefficient intravenous virus delivery to tumors and (2) the lack of
      predictive, immunocompetent preclinical models. To overcome these hurdles, we
      developed JX-594, a targeted, thymidine kinase(-) vaccinia virus expressing human
      GM-CSF (hGM-CSF), for intravenous (i.v.) delivery. We evaluated two
      immunocompetent liver tumor models: a rabbit model with reproducible, time
      dependent metastases to the lungs and a carcinogen-induced rat liver cancer
      model. Intravenous JX-594 was well tolerated and had highly significant efficacy,
      including complete responses, against intrahepatic primary tumors in both models.
      In addition, whereas lung metastases developed in all control rabbits, none of
      the i.v. JX-594-treated rabbits developed detectable metastases. Tumor-specific
      virus replication and gene expression, systemically detectable levels of hGM-CSF,
      and tumor-infiltrating CTLs were also demonstrated. JX-594 holds promise as an
      i.v.-delivered, targeted virotherapeutic. These two tumor models hold promise for
      the optimization of this approach.

PMID- 16905463
TI  - Are happy chickens safer chickens? Poultry welfare and disease susceptibility.
AB  - 1. Contaminated chicken meat remains an internationally important vehicle for
      human infection with Salmonella and Campylobacter spp. In addition, the last 20
      years has seen an international pandemic of human salmonellosis caused by the
      contamination of eggs with Salmonella Enteritidis. 2. It has been a long held
      scientific view that Campylobacter spp. and most, if not all of the common
      zoonotic salmonella, are essentially commensal in chickens. They usually form
      part of the gut flora and contaminate chicken carcases, for example, by faecal
      spillage at slaughter. Even when certain salmonella serovars like S. Enteritidis
      are invasive in laying hens overt evidence of clinical disease is rare and the
      birds appear to behave normally. 3. Are these bacteria just 'passing through' the
      avian host and only transient members of the bacterial flora or is there a more
      dynamic perspective to this infection/colonisation process? Chickens mount
      antibody responses to both pathogens, which indicate something other than
      commensalism. Such immune responses, however, do not always result in the
      clearance of the pathogen. 4. Not all animals in a group will carry salmonella or
      campylobacter, even under experimental conditions, and will vary, especially
      those that are outbred, in their responses to pathogen challenge. Identifying the
      reasons behind this could have important implications for disease control. 5.
      Both salmonella and campylobacter are more likely to be found in animals, which
      are compromised and this may explain at least part of the variations seen.
      Animals are more susceptible to infection when they are in a poor environment,
      fed a poor diet and/or under physical or psychological stress. 6. Work in this
      area has naturally focused on pathogens of medical significance and has shown
      that neurotransmitters such as noradrenaline can markedly alter pathogen
      behaviour. Other host responses like Interferon gamma can also affect host
      tissues in a way, which facilitates invasion by pathogens and may also interact
      directly with certain bacteria. 7. From a food safety perspective, there is
      evidence that egg contents contamination in ovo may be linked to transient stress
      in the hen. Current work at the University of Bristol on the epidemiology of
      campylobacter in broiler production is also showing a potential link between gut
      health and campylobacter colonisation and challenging the concept that these
      bacteria are common commensals. 8. The poor economic returns received by the egg
      and poultry industries mean that intensive production methods are common. Is it
      possible to rear chickens under these conditions in such a way as to exclude
      zoonotic pathogens like salmonella and campylobacter? Data from the UK strongly
      suggest that this is possible with the former pathogen. Can similar advances be
      achieved with campylobacter?

PMID- 16905465
TI  - A review of lighting for broiler breeders.

PMID- 16905466
TI  - On-farm quantification of sustainability indicators: an application to egg
      production systems.
AB  - 1. On-farm quantification of sustainability indicators (SI) is an effective way
      to make sustainable development measurable. The egg production sector was used as
      a case study to illustrate this approach. 2. The objective was to select SI for
      economic, ecological and societal issues, and to analyse the performance on
      selected SI of different production systems. 3. For the case study, we compared 4
      egg production systems, characterised by differences in the housing systems which
      are most common in the Netherlands: the battery-cage system, the deep-litter
      system with and without outdoor run, and the aviary system with outdoor run. 4.
      Based on a clear set of criteria, we selected SI for animal welfare, economics,
      environmental impact, ergonomics and product quality. 5. We showed that on-farm
      quantification of SI was an appropriate method to identify the strengths and
      weaknesses of different systems. 6. From this analysis it appears that the aviary
      system with outdoor run is a good alternative for the battery-cage system, with
      better scores for the aviary system on animal welfare and economics, but with
      worse scores on environmental impact.

PMID- 16905467
TI  - On-farm assessment of environmental enrichment for broiler breeders.
AB  - 1. A field experiment was conducted with commercial broiler breeder females to
      assess the hypothesis that the provision of bunches of string and bales of wood
      shavings would provide attractive environmental enrichment and improve welfare by
      decreasing aggression and feather damage. 2. The experiment was a randomised
      block factorial design conducted in a commercial flock of 21,600 female broiler
      breeders in 12 pens of 1800 chicks. Treatments were environmental enrichment (4
      plastic coated bales of wood shavings and 50 bunches of string) from hatch (EE1)
      or 8 weeks of age (EE2) and a control treatment with no environmental enrichment.
      There were 4 replicates (rooms). 3. Bird activity was videotaped at 5, 10 and 16
      weeks of age and subsequently scored for the number of birds using the perch or
      pecking at a bale, drinker, litter and section of the wall at 10-min intervals
      for 4 h throughout the photoperiod (24 times/d). Aggression was assessed by
      determining the number of aggressive acts in 2-min intervals during 8 periods of
      the day. The skin and feather condition of 25 birds in each pen were scored at 6,
      12 and 18 weeks and the condition of the string bunches was scored at the end of
      the experiment. 4. The proportion of birds pecking the bales, wall and litter
      declined and the proportion pecking at the drinker and using the perch increased
      with age. The number of birds pecking at the bale was similar in EE1 and EE2 at
      10 and 16 weeks of age. 5. The string bunches were not extensively used. The
      condition of the bunches of string in EE2 was worse than in EE1 at the end of the
      experiment. 6. The number of aggressive acts increased with age and there was no
      consistent difference between treatments. 7. There was an increase with age in
      the damage score for feathers over the back and wings and around the tail and
      vent but no differences between treatments.8. Provision of litter in the form of
      unopened bales of wood shavings was a commercially acceptable form of
      environmental enrichment, but there was no evidence that behavioural changes
      associated with feed restriction, including the prevalence of aggression, were
      improved.

PMID- 16905468
TI  - Age-related changes in the intramuscular distribution of melanocytes in the Silky
      fowl.
AB  - 1. The characteristics of melanocyte distribution in skeletal muscles in the
      Silky fowl were investigated in association with growth. 2. Pectoralis (PT) and
      iliotibialis lateralis (ITL) muscles from 1-, 3-, 5-, 10-, 20- and 30-week-old
      Silky males were weighed and collagen type I was detected in frozen sections
      immunohistochemically. 3. Melanocytes were observed in the collagen type I
      immunopositive endomysium and perimysium in both muscles. 4. Image analysis
      indicated that the total area occupied by melanocytes in histological sections
      sharply decreased from 0.61% to 0.16% in PT muscle and from 1.67% to 0.33% in ITL
      muscle at 1 to 3 weeks, and then gradually decreased. The melanocyte area was
      larger in ITL muscle than in PT muscle until 10 weeks of age. 5. We concluded
      that the proportion of intramuscular melanocytes in the Silky fowl differs
      between types of muscles in the early stages of development, and it decreases
      with growth.

PMID- 16905469
TI  - Effects of nutritional level on muscle development, histochemical properties of
      myofibre and collagen architecture in the pectoralis muscle of male broilers.
AB  - 1. The effects of nutritional level on muscle development, histochemical
      properties of myofibre and collagen architecture in the pectoralis muscle were
      evaluated using male broilers of Red Cornish x New Hampshire stock, reared on
      diets of high nutritional value for up to 80 d (H80d) and low nutritional value
      for up to 80 d (L80d, same age as H80d) or 95 d (L95d, same body weight as H80d).
      2. The total live weight and the weight of pectoralis muscle were lower in L80d
      than in both H80d and L95d. The muscle weight as a percentage of live weight was
      8.7% in L80d, 10.7% in H80d and 11.5% in L95d. 3. Pectoralis muscle was composed
      only of type IIB myofibres and showed no differences in myofibre type composition
      among the chicken groups. The largest diameter of type IIB myofibres was observed
      in L95d, followed by H80d and the smallest in L80d. 4. The total amount of
      intramuscular collagen did not differ among the chicken groups (1.92 to 1.99
      mg/g). Types I and III collagens were immunohistochemically detected in both the
      perimysia and endomysia. The thin perimysia around the primary myofibre fascicles
      showed larger width in H80d than L80d and L95d, and also the thick perimysia
      around the secondary fascicles in H80d than L80d. 5. The collagen structure of
      the perimysium was most developed in H80d, followed by L95d and on the least in
      L80d. The development of perimysial collagen fibres could be enhanced by a rapid
      growth rate of the muscle induced by high nutritional level and depressed by a
      slow growth rate with low nutritional foods. 6. The endomysial collagen
      architecture was observed as a felt-like tissue of the fibril bundles with many
      slits. The thinnest endomysial wall was observed in L80d, followed by H80d and
      the thickest in L95d. 7. From these results, it was indicated that foods of high
      nutritional value could enhance growth of the pectoralis muscle of broilers, and
      this is accompanied by hypertrophy of the type IIB myofibres and development of
      the perimysial collagen architecture.

PMID- 16905470
TI  - Association between heterophil/lymphocyte ratio, a marker of 'resistance' to
      stress, and some production and fitness traits in chickens.
AB  - 1. A stock of cross-bred CD hens was divided into 'resistant' (R) and 'sensitive'
      (S) to stress on the basis of the heterophil/lymphocyte (H/L) ratio using the
      lower 99% confidence limit method for selection. A first generation was produced
      from these R and S females mated with similarly selected R and S local Barred
      males. The association between 'resistance' and some production traits was
      investigated. 2. The proportions of R:S among CD females and Barred males was
      51.2:48.8 and 52:48, respectively. Mean H/L ratios for Barred males and females,
      respectively, were 0.87 +/- 0.03 and 0.83 +/- 0.03 (P > 0.05). 3. Compared with
      the S group in CD females, the R group had greater egg production (59% vs 51%),
      egg weight (65.5 g vs 62.6 g) and body weight at 39 weeks (115 g heavier). 4. The
      superiority of R in terms of proportion of fertile eggs, hatchability and the
      proportion hatched from those set amounted to 4.8, 6.1 and 5.4%, respectively. 5.
      The proportion of dead embryos in the R group (5.4%) was lower than in the S
      group (9.3%). 6. With the F1 generation the R chicks were heavier at hatching. 7.
      Percentage mortality of male F1 chicks, from hatching to 4 weeks and from 4 to 8
      weeks, was lower in the R group. A similar, but non-significant, trend was noted
      for R females. 8. The progeny of the R group was heavier than the S progeny at 4
      and 8 weeks and also the percentage dressed weight of males was greater at 8
      weeks. The R group was heavier than the S group at 4, 8 and 12 weeks. 9. These
      results suggest that selection for general 'resistance', on the basis of the H/L
      ratio using the 99% lower confidence limit method of selection, is positively
      correlated with several important production and reproduction traits.
      Establishing resistant lines with high production rates seems feasible.

PMID- 16905472
TI  - PFGE and PCR/RFLP typing of Campylobacter jejuni strains from poultry.
AB  - 1. Pulsed-field gel electrophoresis (PFGE) and PCR-restriction fragment length
      polymorphisms of the flagellin gene (fla-RFLP) were used to analyse 92 poultry
      and 110 human strains of Campylobacter jejuni. 2. Among poultry strains, 11 fla
      RFLP and 11 PFGE subtypes were found, while human strains could be divided into
      23 fla-RFLP and 32 PFGE subtypes. Altogether, 31 fla-RFLP and 32 PFGE subtypes
      were found. 3. The results show that individual flocks in farms are mostly
      infected with a single C. jejuni clone, while during subsequent colonisation
      their genotypes altered. fla-RFLP and PFGE profiles in poultry and humans were
      identical in less than 6% of cases. The results found so far confirm previous
      findings that chicken meat does not represent as important a source of
      campylobacteriosis as was previously believed. 4. The typing of Campylobacter sp.
      forms the basis for an evaluation of the current state and risk assessment of
      various Campylobacter sp. sources in relation to humans. Examination of samples
      with only one method is insufficient for epidemiology studies, because apparently
      different clones identified with one method could originate from a single clone,
      which could be proved with the other method.

PMID- 16905471
TI  - Tissue and allelic-specific expression of hsp70 gene in chickens: basal and heat
      stress-induced mRNA level quantified with real-time reverse transcriptase
      polymerase chain reaction.
AB  - 1. The 70 kDa heat shock proteins (hsp70) are a family of molecular chaperones,
      which promote protein folding and participate in many cellular functions. The
      objective of the current research was to investigate the relationship between
      tissue or allele and the expression of chicken hsp70 under normal growth
      conditions and during acute heat stress (44 degrees C for 4 h). 2. A total of 279
      individuals were genotyped for two single nucleotide polymorphisms (A258G and
      C276G) in chicken hsp70 gene by single-strand conformation polymorphism (SSCP)
      analysis. 3. The mRNA abundance of chicken hsp70 genes was evaluated by real-time
      reverse transcriptase polymerase chain reaction (RT-PCR). The expression of hsp70
      gene in the liver (9.83 +/- 0.84, 10(7)) was significantly higher than that in
      the muscle (4.42 +/- 0.36, 10(7)) under normal growth conditions. However, during
      acute heat stress, the expression of hsp70 gene in the brain (1.82 +/- 0.25,
      10(9)) was the highest and was significantly different from those in the liver
      (1.08 +/- 0.16, 10(9)) and muscle (1.08 +/- 0.13, 10(9)). 4. The expression of
      hsp70 among different genotypes or haplotype combinations is quite different
      under normal and heat-stress conditions. The haplotype H3 (GC) is probably
      advantageous to improving heat resistance of chickens. 5. The results from the
      present study indicate that the expression of hsp70 in chickens is affected by
      heat stress, and is tissue- and allele-dependent.

PMID- 16905473
TI  - Probability of an egg cracking during packing can be predicted using a simple non
      destructive acoustic test.
AB  - 1. The aim of this investigation was to test the predictive power of the dynamic
      stiffness measurement to identify eggs which are most likely to crack under field
      conditions. 2. A representative sample of eggs (n = 1660) was collected from the
      front of the cages in a commercial battery unit. Egg weight, % damping and
      dynamic stiffness (Kdyn) were recorded using an acoustic crack detection device.
      Intact eggs were marked and replaced in the front of the cages. These eggs were
      subsequently passed through online collection, grading and packing machinery,
      along with a volume of unmarked eggs. At the end of packing the acoustic test was
      repeated on the marked eggs, and these were subsequently categorised as being
      either intact (0) or cracked (1). 3. A logistic regression of the probability of
      cracking vs Kdyn revealed that as the Kdyn measurement decreases below 15,000 N/m
      there is a rapid increase in the probability that an egg will crack during
      routine handling. 4. Additional variables (visit, egg weight,% damping and
      position in the house (battery [1 to 7], side [1, 2] and tier [1 to 8]) were also
      fitted to the model but only egg weight, visit and tier effects significantly
      improved the model fit. 5. This study confirms that the dynamic stiffness
      measurement can predict the probability of an egg cracking in the field and with
      high precision. As this measurement also has a high heritability, it could be
      incorporated into breeding programmes, where it would offer an excellent method
      to improve eggshell quality and reduce the incidence of cracked eggs.

PMID- 16905474
TI  - Effect of dietary conjugated linoleic acid (CLA) on broiler performance, serum
      lipoprotein content, muscle fatty acid composition and meat quality during
      refrigerated storage.
AB  - 1. A trial was conducted to investigate the effects of dietary conjugated
      linoleic acid (CLA) concentration on performance parameters, carcase composition,
      thiobarbituric acid reactive substances (TBARS) and fatty acid composition in leg
      and breast muscle and serum lipoprotein concentrations. 2. A total of 128 male
      chickens were allocated to 4 dietary treatments (0, 1, 2 and 3% CLA) and given a
      standard starter diet from d 1 to d 21 and a finisher diet from d 22 to d 42.
      Breast and leg muscles were stored at 4 degrees C for 1, 3 or 7 d. Fatty acid
      composition, TBARS and pH were determined in muscles. 3. Weight gain and feed
      conversion ratio were positively influenced by dietary CLA level. CLA isomer
      concentration in muscles increased linearly (P < 0.01) as dietary CLA increased.
      Addition of CLA to feeds significantly increased saturated fatty acid (SFA) and
      polyunsaturated fatty acid (PUFA) and decreased (P < 0.01) monounsaturated fatty
      acid (MUFA) in leg and breast tissues. 4. Muscle pH decreased with duration of
      refrigerated storage. TBARS values were significantly (P < 0.01) influenced by
      dietary CLA and storage time. CLA increased total cholesterol, LDL-cholesterol
      and HDL-cholesterol, but reduced triglycerides in the plasma of broilers.

PMID- 16905475
TI  - Prediction of ingredient quality and the effect of a combination of xylanase,
      amylase, protease and phytase in the diets of broiler chicks. 1. Growth
      performance and digestible nutrient intake.
AB  - 1. A total of 2208 broiler chicks were used in two growth experiments (8
      treatments and 12 replicate pens in each experiment) to assess the effects of
      xylanase, amylase, protease and phytase in maize-based diets. 2. A positive
      control diet was formulated containing adequate nutrient concentrations. A
      negative control diet was formulated to contain approximately 628 kJ/kg, 0.13%,
      0.12% and 1 to 2% less metabolisable energy (ME), phosphorus (P), calcium (Ca)
      and amino acids, respectively, than the positive control. In addition, two
      further negative control diets that contained 167 or 334 kJ/kg more ME,
      respectively, than negative control 1 were formulated. 3. A further 4 dietary
      treatments were made by supplementing each of the 4 negative control diets with a
      combination of xylanase, amylase, protease and phytase, resulting in 8 dietary
      treatments in a 4 by 2 factorial arrangement. 4. The scale of the removal of
      energy, P, Ca and amino acids from the positive control diet was determined using
      least square models based on in vivo data for both the xylanase/amylase/protease
      cocktail and for phytase and it was predicted that performance of birds fed on
      negative control 1 would be returned by supplemental enzymes to that of those fed
      on the positive control. 5. In both experiments there was a significantly poorer
      performance in birds fed on the negative control 1 than in those fed on the
      positive control. The poorer weight gain and feed conversion ratio could be
      attributed in part to a reduced intake of digestible energy, P, nitrogen (N) and
      amino acids associated with birds fed on the negative control diet. 6.
      Supplementation of the negative control diets with the enzyme combination
      returned performance to that of the positive control in both experiments. 7.
      These data indicate that exogenous xylanase, amylase, protease and phytase can be
      used successfully in a strategically formulated low nutrient density diet to
      maintain performance to that of birds fed on a nutritionally adequate diet.

PMID- 16905476
TI  - Prediction of ingredient quality and the effect of a combination of xylanase,
      amylase, protease and phytase in the diets of broiler chicks. 2. Energy and
      nutrient utilisation.
AB  - 1. In order to investigate the effects of xylanase, amylase, protease and phytase
      in the diets of broiler chickens containing graded concentrations of
      metabolisable energy (ME), two 42-d experiments were conducted using a total of
      2208 broiler chicks (8 treatments with 12 replicate pens in each experiment). 2.
      Four diets including one positive and three negative control diets were used.
      Three maize/soybean meal-based negative control (NC) diets were formulated to be
      identical in available phosphorus (P), calcium (Ca) and amino acids but NC1
      contained approximately 0.17 MJ/kg less ME than NC2 and approximately 0.34 MJ/kg
      less ME than NC3. A positive control (PC) was fed for comparison and was
      formulated to be adequate in all nutrients, providing approximately 0.63 MJ/kg
      ME, 0.13% available P, 0.12% Ca and 1 to 2% amino acids more than NC1. 3. The
      reduction in nutrient density between NC1 and PC was determined using ingredient
      quality models Avichecktrade mark Corn and Phychecktrade mark that can predict
      the response to exogenous enzymes in maize/soybean meal-based broiler diets.
      Supplementation of each diet with or without a cocktail of xylanase, amylase,
      protease and phytase gave a total of 8 dietary treatments in a 4 x 2 factorial
      arrangement. The same treatments and diet designs were used in both experiments
      but conducted in different locations using different batches of maize, soybean
      meal and minor ingredients. 4. In both experiments, digestibility was improved by
      the addition of exogenous enzymes, particularly those for P, Ca and certain amino
      acids. In addition, the supplementation of the PC with enzymes elicited a
      positive response indicating that over-the-top addition of xylanase, amylase,
      protease and phytase may offer a nutritionally and economically viable
      alternative to feed cost reduction. 5. It can be concluded that the digestibility
      of nutrients by broilers fed on maize/soybean meal-based diets can be improved by
      the use of a combination of xylanase, amylase, protease and phytase.

PMID- 16905477
TI  - Effects of commercial enzyme preparations on egg and eggshell quality in laying
      hens.
AB  - 1. Four different commercial enzyme products were added to standard commercial
      layer diets, based on barley, wheat or triticale. 2. Diets were fed to 4
      different strains of commercial laying hen: ISA Brown, Hy-Line CB, Tegel SB2 and
      Tegel HiSex. 3. Diets were given for 5 weeks prior to measurements of egg and
      eggshell quality. 4. The inclusion of commercial enzyme products in the diets had
      no effect on egg weight. 5. Positive effects of the enzymes were: improved
      eggshell breaking strength, shell weight, percentage shell and shell thickness
      for the barley-based diet and increased eggshell breaking strength for two of the
      enzymes with the wheat-based diets. 6. Negative effects of the enzyme products
      were slightly lighter coloured eggshells and reduced albumen quality for the
      barley-based diet and for two enzymes with the wheat-based diet. 7. The addition
      of commercial enzyme preparations had no main effect on egg and eggshell quality
      for the triticale-based diet, except for effects on yolk colour. 8. Yolk colour
      was lower than control for enzyme 3 in all diets and for enzyme 4 with the barley
      and wheat-based diets. 9. Further investigation is required to elucidate the
      specific enzyme components that influence egg quality.

PMID- 16905479
TI  - Effect of stachyose supplementation on growth performance, nutrient digestibility
      and caecal fermentation characteristics in broilers.
AB  - 1. The objective of this study was to evaluate whether the oligosaccharide
      stachyose enhances gastrointestinal tract health by fermentation and
      proliferation of desirable bacteria species and thus affects growth performance
      and nutrient digestibility in broilers. 2. A total of 432 1-d-old male Arbor
      Acres (AA) broilers were randomly allocated to one of 6 treatments, with 12
      replicate pens per treatment and 6 birds per pen. Chicks were fed a maize-hamlet
      protein 300 (HP300) basal diet with 0, 4.0, 8.0, 12.0 or 16.0 g/kg stachyose. A
      sixth diet contained no HP300 but soybean meal (SBM) and provided 8.7 g/kg
      stachyose and 3.1 g/kg raffinose. The duration of the study was 42 d. 3.
      Stachyose contents above 12.0 g/kg depressed group body weights, average daily
      gain and feed/gain but not feed intake during the whole experimental period.
      Broiler growth decreased linearly and quadratically with increasing stachyose
      content. No differences were detected between diets supplemented with 12.0 g/kg
      stachyose and SBM. 4. Nutrient digestibility tended to decrease but not
      significantly with increasing stachyose. 5. Stachyose content had no significant
      positive effects on caecal pH, microflora population and the resulting short
      chain fatty acid (SCFA) metabolites during the 42 d experiment, with only
      butyrate differing significantly in the initial period.

PMID- 16905482
TI  - Older people and the interprofessional agenda.

PMID- 16905478
TI  - Effect of higher levels of dietary selenium on production performance and immune
      responses in growing Japanese quail.
AB  - 1. The effect of increasing dietary selenium (Se) on production performance and
      immune responses in growing (0 to 6 weeks) Japanese quail was investigated. 2.
      One-day-old chicks (240) were randomly selected and divided into 12 groups with
      20 chicks in each group (3 dietary treatments x 4 replicates). The basal diet
      contained 0.2 mg Se/kg and the two experimental diets were supplemented with 0.5
      and 1.0 mg Se/kg. 3. Body weight gain, food intake and food conversion ratio and
      mortality were not affected by Se supplementation. 4. On d 28, antibody responses
      to inoculated sheep red blood cells were determined. Antibody titres were
      significantly higher after feeding the two Se-supplemented diets. 5. During week
      4, the response to intradermally injected phytohaemagglutinin, an index of the in
      vivo cell-mediated immune response, was shown to be increased in the groups fed
      on the Se-supplemented diets. 6. After 6 weeks, the relative weights of the bursa
      of Fabricius and thymus were greater in the chicks given the Se-supplemented
      diets but there was no effect on the relative weight of spleen and liver. 7. It
      is concluded that supplementing the diet with Se has a beneficial effect on
      immune responses but does not affect production performance in growing Japanese
      quail.

PMID- 16905480
TI  - Effect of vaginal douching and different semen extenders on bacterial load and
      fertility in turkeys.
AB  - 1. A study on artificial insemination of Beltsville Small White turkeys
      investigated the effect on bacterial load and fertility of vaginal douching with
      diluents containing Gentamicin 400 microg/ml and different semen extenders. 2.
      Irrespective of the extenders used, vaginal douching with Gentamicin reduced the
      microbial load of the vagina with resultant improvement in fertility and
      hatchability and corresponding reduction in embryonic mortality. 3. Eggs from
      hens inseminated with semen extended with Beltsville Poultry Semen Extender
      (BPSE) diluent along with vaginal douching showed a trend towards higher per cent
      fertility and per cent hatchability of total and fertile eggs set compared to
      other extenders, though this was non-significant.

PMID- 16905483
TI  - Care management for older people: does integration make a difference?
AB  - England and Northern Ireland provide examples of different degrees of integration
      of health and social care within broadly similar administrative and funding
      frameworks. This paper examines whether integrated structures appear to impact
      upon the operation of care management, a key approach to providing coordinated
      care for vulnerable older people. There appeared to be more evidence of
      integrated practice between health and social care in Northern Ireland than
      England, although some key features, such as intensive care management, were no
      more evident. It is concluded that further investigation is required as to the
      extent to which integrated structures have impacted upon patterns of professional
      working and underlying beliefs about roles.

PMID- 16905484
TI  - Communication in interdisciplinary team meetings: what are we talking about?
AB  - Interdisciplinary teams are central to the care of the older patient in long-term
      care settings. Critical to the success of caring for these patients is the
      communication between providers about patient care. This study examines
      professional communication practices in interdisciplinary team meetings, a common
      forum for discussing patient care. Two teams at a long-term care facility
      specializing in patients with Alzheimer's participated in this qualitative
      exploratory study. All team members participated in semi-structured interviews.
      In addition, seven team meetings in which 31 patients were discussed were audio
      and video taped. Team members discussed the importance of team meetings to help
      coordinate care provided to patients, while also expressing concern about the
      effectiveness of the meetings to reach this goal. Through detailed discourse
      analyses of transcripts of the meetings, we identified three different
      communication practices in team meetings: giving report, writing report, and
      collaborative discussion. Only the latter practice met the goals indicated by the
      team members to coordinate and make joint decisions about patient care and
      allowed for team members to collaboratively solve problems. We discuss one case
      study to exemplify how the use of these communication practices results in the
      omission of information central to making decisions regarding patient care.

PMID- 16905485
TI  - Implementing the Single Assessment Process: opportunities and challenges.
AB  - The Single Assessment Process (SAP) has been introduced as part of the National
      Service Framework for Older People and has major implications for health and
      social care. The aim of this study was to evaluate a pilot introduction of the
      Single Assessment Process in the South-East of England. A qualitative case study
      design incorporating observation and semi-structured interviews were used to
      collect data. Assessment visits were observed and recorded, and interviews were
      carried out with older people and their carers (n = 9), health and social care
      practitioners, operational managers, and other key individuals involved in the
      pilot (n = 26). Overall the evaluation found three major themes that had an
      impact on the implementation of the Single Assessment Process. These were: the
      process of implementing policy and change, the health and social care boundary,
      and communication and sharing of assessments. Front-line practitioners (street
      level bureaucrats) had a major impact on the SAP implementation, particularly
      through their reluctance to engage with the process, work together and share
      assessments. Success of the national SAP implementation will depend on the extent
      to which those working directly with older people can be engaged in the policy
      process.

PMID- 16905486
TI  - Physicians' expectations regarding registered nurses caring for older people
      living in sheltered housing, retirement homes and group dwellings.
AB  - The aim of this study was to illuminate the meaning of the physicians'
      expectations regarding registered nurses who are responsible for the care of
      older people living in sheltered housing, retirement homes and group dwellings. A
      phenomenological-hermeneutic method was used for the analysis. Twelve physicians
      from two municipalities in Sweden were interviewed. The naive reading of the
      interviews characterizes the physicians' expressed views of nurses by using
      metaphors such as "the extended arm", "gatekeeper" and "belonging to a no-man's
      land". In the structural analysis, explanations of the metaphors are given. The
      new understanding was that the physicians also expect registered nurses to be
      able to switch between keeping a distance and being close to older people. When
      registered nurses have this skill, the physicians have a "we" feeling towards the
      nurse. The paper provides insights into the physician-nurse relationship, in the
      context of residential care in Sweden.

PMID- 16905487
TI  - Interprofessional support of mental well-being in schools: a Bourdieuan
      perspective.
AB  - There is increasing international concern about the mental health and well-being
      of school-aged children, and the school is often seen as the optimum setting to
      deliver interagency interventions. This paper draws on a Scottish study examining
      the responses of local authorities, schools and other agencies to challenging
      behaviour related to poor mental health. It explores the ways in which the
      presence of workers from other agencies had an impact on the capacity of schools
      to respond to such issues. In Bourdieuan terms, the study showed that non
      teaching workers imported into school developed new forms of 'habitus' leading to
      effective team work to support vulnerable pupils, but that they often operated in
      isolation from the wider teaching staff. Different professional cultures created
      significant barriers, which could be exacerbated by active resistance to
      meaningful engagement. Consequently, parallel working evolved, where staff from
      agencies other than education supported pupils experiencing difficulties, but
      there was little evidence of corresponding changes to ethos or pedagogy to meet
      the needs of pupils in school. Expertise pertaining to the mental well-being of
      pupils thus tended to be compartmentalized and was not readily transferred
      elsewhere, and this led to a disjointed experience for pupils. Our evidence
      strongly suggested that teachers preferred to learn from other teachers. This
      served to reinforce existing habitus and to isolate them from new ways of
      thinking. Potential ways of effecting culture change are suggested, through
      innovative training and development, linked to accountability, to challenge the
      new mode of parallel working before it becomes the status quo.

PMID- 16905488
TI  - Leadership in interprofessional collaboration - the case of childcare in Norway.
AB  - This study addresses leadership in interprofessional collaboration in childcare
      services (residential care). The aim was to explore the managers' (n = 6)
      experiences and present their views on how they exercised leadership in the
      residential institutions as well as how they organized and facilitated
      collaboration with relevant professionals and service users. Data was collected
      through open interviews. Qualitative content analysis was used to analyse the
      interviews, and three categories emerged; "external responsibility", "sustaining
      communication" and "internal responsibility". The overarching concept was
      identified as "facilitating interaction processes and ensuring cohesion". The
      main findings were related to the managers' experiences of linked processes of
      leadership and collaboration, perceptions of the structures of communication,
      their responsibility as well as the interaction processes. The managers exercised
      leadership in terms of self-governance and co-governance, and used strategies,
      such as governing images and influencing the voluntary aspect of collaboration.

PMID- 16905489
TI  - Occasioning learning in the workplace: the case of interprofessional peer
      collaboration.
AB  - In this study, we explore the potential of peer collaboration as a means of
      promoting continuous learning at work. Six peer collaboration groups comprised of
      18 employees in a large urban health region in Canada participated in small
      collaborative inquiry groups over a period of 6 - 8 months. Using a collective
      case study design, each group provided one instrumental case that when combined
      with the other five served a supportive role in studying peer collaboration in
      continuous professional education. In this article, drawing on analysis of
      transcribed group conversations, we provide portraits of two interprofessional
      peer groups for in-depth discussion and further illustration. While one group
      used peer collaboration to: (1) retrace and reconsider their practical judgments;
      and (2) identify and explore breakdowns in practice, the other group demonstrated
      that peer collaboration can provide a space in which to identify and explore
      issues related to (1) workplace conflict, (2) professional boundaries and (3)
      emotional pain. The power of peer collaboration as an informal vehicle for
      continuous learning seems to lie in interprofessional conversation. This study
      suggests that unstructured but focused conversations about daily practice, among
      close colleagues from other professions, can yield surprising possibilities for
      learning.

PMID- 16905491
TI  - Interprofessional collaboration: sure start, uncertain futures.

PMID- 16905490
TI  - The professional subcultures of students entering medicine, nursing and pharmacy
      programmes.
AB  - This study sought to determine the attitudes, beliefs and values towards clinical
      work organization of students entering undergraduate medicine, nursing and
      pharmacy programmes in order to frame questions for a wider study. In the Faculty
      of Medical and Health Sciences, The University of Auckland students entering
      medicine, nursing and pharmacy programmes completed a questionnaire based on that
      used by Degeling et al. in studies of the professional subcultures working in the
      health system in Australia, New Zealand, England and elsewhere. Findings indicate
      that before students commence their education and training medical, nursing and
      pharmacy students as groups or sub-cultures differ in how they believe clinical
      work should be organized. Medical students believe that clinical work should be
      the responsibility of individuals in contrast to nursing students who have a
      collective view and believe that work should be systemized. Pharmacy students are
      at a mid-point in this continuum. There are many challenges for undergraduate
      programmes preparing graduates for modern healthcare practice where the emphasis
      is on systemized work and team based approaches. These include issues of
      professional socialization which begins before students enter programmes,
      selection of students, attitudinal shifts and interprofessional education.

PMID- 16905492
TI  - Family health teams: a new Canadian interprofessional initiative.

PMID- 16905501
TI  - Toxicity and drug interactions of herbs and dietary supplements.

PMID- 16905502
TI  - Clinical approach to adverse events and interactions related to herbal and
      dietary supplements.

PMID- 16905503
TI  - Safety of ethnic & imported herbal and dietary supplements.

PMID- 16905504
TI  - Safety evaluation and adverse events monitoring by poison control centers: a
      framework for herbs & dietary supplements.

PMID- 16905506
TI  - Jimsonweed (Datura stramonium) exposures in Texas, 1998-2004.
AB  - For centuries, jimsonweed, Datura stramonium, was known to produce hallucinogenic
      effects. Jimsonweed is easily obtained and may be abused by adolescents. This
      investigation examined the patterns of jimsonweed exposures reported to Texas
      poison control centers during 1998-2004. A total of 188 reported human exposures
      were identified. Seventy-six percent of the exposures occurred in June-October.
      For those cases where the information was known, the majority were male (82%) and
      age 13-19 yr (72%). Intentional abuse or misuse accounted for 78% of reported
      exposures. Eighty-two percent of the reported exposures were at, en route to, or
      referred to health care facilities, and 89% of those cases with a known medical
      outcome had moderate or major effects. The most frequently reported clinical
      effects were hallucination, tachycardia, agitation, mydriasis, and confusion; the
      most frequently reported treatments were intravenous fluids replacement,
      activated charcoal, cathartic, and benzodiazepines. The pattern of reported
      jimsonweed exposures in Texas was consistent with previously published
      literature.

PMID- 16905507
TI  - Responses of shortfin eel (Anguilla australis) exposed in situ to pulp and paper
      effluent.
AB  - The responses of shortfin eel (Anguilla australis) to discharges from two pulp
      and paper mills, municipal wastewater, and a geothermal power plant wastewater
      were examined. Eels were caged at 3 sites along the Tarawera River, North Island,
      New Zealand, to explore effects of a 3-wk exposure down a contamination gradient
      (Ref --> D1 --> D2). Most of the observed effects were seen in eels caged at the
      furthest downstream site (D2), below all the discharge areas. General hematology
      in eels was unaffected, as measures did not differ markedly at the two downstream
      sites compared with the reference site. At D2, eels were significantly lighter
      per unit length (reduced condition factor), although liver and spleen size (LSI
      and SSI) were unaffected. Significantly elevated circulating sex steroid
      concentrations (testosterone and estradiol) were measured in D2 eels and
      increasing sex steroid levels at both sites downstream of the reference site were
      observed. Significant ethoxyresorufin O-deethylase (EROD) activity induction was
      seen in D2 eels and bile chemistry showed significant accumulation of pyrene and
      retene equivalents. However, significantly greater concentrations of total resin
      acids were found in the bile of eels from the intermediate site (D1), between the
      two pulp and paper mills. The higher polycyclic aromatic hydrocarbon (PAH)
      equivalents found in the bile of D2 eels suggest that resin acid neutrals,
      particularly retene, are responsible for some of the effects observed in eels at
      the furthest downstream exposure site. Levels of pulp and paper mill extractives
      in sediment, including the PAH retene, support this conclusion.

PMID- 16905508
TI  - Biological markers of fetal lead exposure at each stage of pregnancy.
AB  - It has been suggested that plasma lead (Pb) represents the fraction of
      circulating Pb that crosses the placenta. Whole-blood Pb levels, the conventional
      method for measuring circulating Pb, may not adequately reflect plasma Pb levels.
      The objective of this study was to assess the relationship between whole-blood
      and plasma Pb in a cohort of pregnant women. A group of 237 pregnant women,
      recruited in Mexico City from 1997 to 1999, was studied. whole-blood and plasma
      lead concentrations were evaluated at 12, 24, and 34 wk of gestation by
      inductively coupled plasma-mass spectrometry. Data were analyzed using a mixed
      effects regression model. An exponential relationship was found between plasma
      and whole-blood Pb levels and significant modification of the association by
      stage of pregnancy. The association was stronger in the second trimester relative
      to the first, and it further increased in the third trimester. The model predicts
      increased plasma Pb levels for a given whole-blood Pb value as pregnancy advances
      for whole-blood Pb levels greater than approximately 110 microg/L, but not for
      blood Pb levels less than 100 microg/L. These findings could be due to
      physiologic changes during pregnancy, such as decreasing hematocrit, saturation
      of red cell Pb binding capacity, and increased bone resorption or intestinal
      absorption. Collectively, these data suggest that at elevated maternal blood Pb
      levels the developing fetus may be at greater risk of Pb exposure from increased
      maternal plasma Pb than otherwise predicted from whole-blood Pb levels.

PMID- 16905509
TI  - Does arsenic exposure increase the risk of development of peripheral vascular
      diseases in humans?
AB  - Arsenic has been well documented as a major risk factor in the development of
      blackfoot disease (BFD), a unique peripheral vascular disease (PVD) endemic to
      the southwestern coast of Taiwan, where residents imbibed artesian well water
      containing excessive amounts of arsenic for more than 50 yr. Long-term arsenic
      exposure was also reported to be associated with mortality attributed to PVD. A
      tap-water supply system was implemented in the early 1960s in the BFD endemic
      areas. Artesian well water was no longer used for drinking and cooking after the
      mid-1970s. The objective of this study was to examine whether mortality
      attributed to PVD decreased after the consumption of artesian well water
      containing high concentrations of arsenic ceased and, if so, when the reduction
      occurred. Standardized mortality ratios (SMRs) for PVD were calculated for the
      BFD endemic area for the years 1971-2003. Cumulative-sum techniques were used to
      detect the occurrence of changes in the SMRs. Data showed that mortality due to
      PVD declined gradually for approximately 25 to 27 yr following cessation of
      consumption of this arsenic artesian well water. Based on the reversibility
      criterion, the association between arsenic exposure and PVD-attributed mortality
      is likely to be causal.

PMID- 16905510
TI  - Measuring cholinesterase activity in human saliva.
AB  - To assess the potential for using saliva in pesticide biomonitoring, the
      consistency of cholinesterase activity in human saliva collected over time was
      examined. In this pilot study, saliva was collected from 20 healthy adults once
      per week for 5 consecutive weeks using 2 different collection methods: a
      disposable plastic pipette, and a cotton-wool roll. A brief questionnaire was
      conducted each week to document changes in exposure to cholinesterase inhibitors
      for the duration of the sampling. To measure cholinesterase activity, an existing
      radiometric method was modified to make it suitable for human saliva. Using this
      method, cholinesterase activity was measurable in saliva, and duplicate samples
      showed reliable repeatability. Activity in both collection methods ranged from 3
      to 265 nmol/h/ml saliva (mean = 52 +/- 37 [SD] nmol/h/ml saliva). For some
      individuals, enzyme activity was consistent over the five sampling weeks; for
      others, activity was highly variable. Coefficients of variation (CVs) were
      calculated to assess variability, and mean CVs were the same for both collection
      methods (about 35%). Adjusting for protein concentration in the pipette-collected
      samples did not change results. Both collection methods worked well for
      collecting between 1 and 3 ml saliva, but at the majority of visits (86%),
      participants preferred the cotton-wool roll. Results from this study suggest that
      saliva may be a useful indicator of potential neurotoxic effects from exposure to
      organophosphorus and carbamate pesticides, but that factors affecting variability
      should be explored further.

PMID- 16905511
TI  - Stakeholder needs for air pollution and health information.
AB  - Within the European Commission-supported thematic network project AIRNET, a
      stakeholder survey was performed to identify key questions and issues of concern
      for end users regarding air pollution and health information. On the whole,
      survey respondents typically asked general questions concerning air pollution and
      health (i.e., regarding the type of pollutant, emission sources, monitoring, and
      health impact). Furthermore, an overwhelming response across all stakeholder
      categories was not the unavailability of information sources to inform policy,
      but the lack of time available to read and absorb all the information. Overall,
      the respondents expressed their preference for information that is (1) presented
      as short and clear overviews, (2) ready for policy use by including a practical
      linkage between the research findings and implementation of public protection,
      and (3) in a format easily passed on to others.

PMID- 16905512
TI  - Intensive insulin therapy in the intensive care unit: update on clinical impact
      and mechanisms of action.
AB  - OBJECTIVE: Hyperglycemia is a common feature of the critically ill and has been
      associated with increased mortality. In this review, we give an overview of
      studies associating critical illness-induced hyperglycemia with adverse outcome
      and describe how mortality and morbidity are affected when blood glucose levels
      are strictly controlled to normoglycemia with intensive insulin therapy. RESULTS:
      Maintaining normoglycemia with intensive insulin therapy improves survival rates
      and reduces morbidity in prolonged critically ill patients in both surgical and
      medical intensive care units (ICUs), as shown by 2 large randomized controlled
      studies. Prevention of cellular glucose toxicity by strict glycemic control
      appears to play a predominant role, but other metabolic and nonmetabolic effects
      of insulin also seem to contribute to the clinical benefits of this therapy.
      CONCLUSION: These data support the generalized implementation of a strict blood
      glucose control management with intensive insulin therapy in adult surgical as
      well as medical ICU patients.

PMID- 16905513
TI  - Clinical effects of hyperglycemia in the cardiac surgery population: the Portland
      Diabetic Project.
AB  - OBJECTIVE: To determine the outcome effects of hyperglycemia, and its
      pharmacologic reduction with continuous intravenous insulin infusions (CII) in
      the cardiac surgery patient population. METHODS: The Portland Diabetic Project is
      a prospective, non-randomized, observational study of 5,510 consecutive diabetic
      cardiac surgery patients treated between January 1987 and November 2005. RESULTS:
      This study was the first to reveal that hyperglycemia in the first 3
      postoperative days is independently predictive of mortality (P<0.0001), deep
      sternal wound infection (P= 0.0001), and increased length of stay (P<0.002) in
      diabetic cardiac surgery patients. Conversely, CII, designed to achieve
      predetermined target glucose levels, was shown to independently reduce the risks
      of death and deep sternal wound infection by 60% and 77%, respectively (P<0.001
      for both). Target glucose levels <150 mg/dL and a 3-day postoperative duration of
      CII therapy are both important variables that determine the impact of the CII
      therapy on improved outcomes. CONCLUSIONS: Perioperative hyperglycemia in cardiac
      surgery patients adversely alters mortality, length of stay, and infection rates.
      Three days of CII eliminates the incrementally increased risks of these
      complications previously seen in diabetic patients.

PMID- 16905515
TI  - The benefits of inpatient diabetes care: improving quality of care and the bottom
      line.
AB  - OBJECTIVE: To analyze the impact of a hospital-wide inpatient diabetes management
      program on quality of care, length of stay, and cost. METHODS: A retrospective
      review was conducted for diabetes identification and treatment in a large
      tertiary care hospital in Oklahoma City, Oklahoma. Cultural change was
      accomplished by educating the healthcare professionals and medical staff. Systems
      were implemented to better identify patients with diabetes and to focus on
      quality improvement. Protocols were developed and implemented as tools for
      improving care. Results were monitored, and quality of care was assessed by
      examining lengths of stay and financial outcomes. RESULTS: Hospital-wide
      training, earlier identification of patients with diabetes, and the
      implementation of inpatient protocols had positive results on both quality of
      care and the hospital's bottom line. More patients with diabetes were identified
      earlier in their stays, care was managed effectively to reduce blood glucose
      levels, lengths of stay were reduced, and coding was improved to more accurately
      reflect the complexity of care provided. CONCLUSION: By increasing diabetes
      awareness hospital-wide and implementing effective identification and management
      systems, hospitals are well positioned to provide higher-quality diabetes care,
      which also translates into a positive impact on the bottom line.

PMID- 16905516
TI  - Financial implications of glycemic control: results of an inpatient diabetes
      management program.
AB  - OBJECTIVE: (1) To determine the financial implications associated with changes in
      clinical outcomes resulting from implementation of an inpatient diabetes
      management program and (2) to describe the strategies involved in the formation
      of this program. METHODS: The various factors that influence financial outcomes
      are examined, and previous and current outcomes are compared. RESULTS:
      Associations exist between hyperglycemia, length of stay, and hospital costs.
      Implementation of an inpatient diabetes management program, based on published
      guidelines, has been shown to increase the use of scheduled medications to treat
      hyperglycemia and increase the frequency of physician intervention for glucose
      readings outside desired ranges. Results from implementing this program have
      included a reduction in the average glucose level in the medical intensive care
      unit through use of protocols driven to initiate intravenous insulin once the
      glucose level exceeds 140 mg/dL. Additionally, glucose levels have been reduced
      throughout the hospital, primarily because of interactions between diabetes nurse
      care managers and the primary care team. Associated with these lower glucose
      levels are a decreased prevalence of central line infections and shorter lengths
      of stay. The reduction in the length of stay for patients with diabetes has
      resulted in a savings of more than 2 million dollars for the year and has yielded
      a 467% return on investment for the hospital. CONCLUSION: Improved blood glucose
      control during the hospitalization of patients with known hyperglycemia is
      associated with reduced morbidity, reduced hospital length of stay, and cost
      savings. The implementation of an inpatient diabetes management program can
      provide better glycemic control, thereby improving outcomes for hyperglycemic
      patients while saving the hospital money.

PMID- 16905514
TI  - Inpatient diabetes: review of data from the cardiac care unit.
AB  - OBJECTIVE: To review prospective and retrospective studies in an effort to assess
      the effect of glucose control on outcomes in critically ill populations. METHODS:
      Results from recent prospective and retrospective studies are presented and
      analyzed in detail, with an emphasis on patients with myocardial infarction.
      RESULTS: Retrospective observations show that, with the routine use of
      percutaneous coronary interventions, hyperglycemia continues to be a risk factor
      for mortality. In 2 prospective studies using glucose-insulin-potassium infusion,
      glucose levels did not reach target, and the results of both trials were negative
      with regard to the primary endpoint, mortality. However, progressive
      hyperglycemia was a risk factor for death in both prospective studies. It is an
      interesting paradox that diabetes actually may be protective for myocardial
      infarction. Although the reasons for this are not clear, one study showed that
      patients with diabetes were more likely to receive insulin for any given blood
      glucose level. CONCLUSION: A study using variable-rate intravenous insulin
      infusion should be commissioned. In the meantime, clinicians should strive to
      achieve the best-possible glucose control in all patients with acute myocardial
      infarction and hyperglycemia. While we improve our understanding of the basic
      roles of glucose and insulin in modulating inflammation, we must aggressively
      treat hyperglycemia to the national goals for this population, which would
      substantially improve outcomes.

PMID- 16905518
TI  - Improving inpatient diabetes care: nursing issues.
AB  - As the epidemic of diabetes continues to escalate, the number of patients with
      diabetes who are hospitalized also will grow. Current evidence shows the value of
      good glycemic control in reducing morbidity and mortality in patients with
      diabetes. Nurses will increasingly be called on to provide the majority of the
      hospitalized care for these patients, and to implement care strategies that are
      safe, efficient, and effective. This article lists barriers faced by nurses in
      the inpatient setting when providing care to patients with diabetes and
      hyperglycemia, describes certain strategies that have successfully overcome these
      barriers, and suggests other strategies for testing.

PMID- 16905517
TI  - Patient safety and inpatient glycemic control: translating concepts into action.
AB  - OBJECTIVE: (1) To summarize current knowledge regarding patient safety issues and
      their impact on inpatient glycemic control and (2) to provide a systematic and
      practical approach to improving patient safety in this area. METHODS: Insulin
      delivery in inpatient settings is examined, as are the barriers to safe insulin
      therapy. A distinction is made between safety strategies of proven value and
      those that are less useful. Characteristics of safer insulin algorithms are
      discussed. RESULTS: Errors in insulin administration remain a common cause of
      injuries. Despite strong evidence of the dangers of sliding-scale insulin
      regimens in inpatient settings, sliding-scale insulin regimens remain a widely
      used but ineffective (and occasionally dangerous) method. To correctly analyze
      inpatient processes of care, a systems approach is needed, and the relationship
      between quality of care, latent medical errors, injurious patient errors, and
      patient safety must be understood. In complex systems such as hospitals,
      catastrophic error has complex roots involving many individuals, and the design
      of the system often has latent flaws that make human error likely, even
      predictable. The concept of the scope of awareness is useful in understanding why
      it is ineffective to focus only on those at the point of care, and how
      improvement is more apt to occur with a team approach and the evaluation of
      systemic factors, at the "blunt end" of care. Error-prone organizations are often
      very unsafe, and certain practices tend to be common among them. Data are now
      available showing the negative impact of poorly supervised trainees and the
      extent of the problem worldwide on patient safety. CONCLUSION: Redesign of
      patient care provided in hospitals regarding glucose control is long overdue.
      Practical strategies are given that focus on improving patient safety for the
      patient needing inpatient glycemic control. Such techniques now have a sufficient
      evidentiary base. Therefore, hospitals should move rapidly to make euglycemia a
      goal for all inpatients, and to make patient safety in glycemic control a
      reality, not just for a few, but for all patients in our care.

PMID- 16905519
TI  - Nutrition therapy for the hospitalized patient with diabetes.
AB  - OBJECTIVE: To summarize recommendations for medical nutrition therapy (MNT),
      including how to implement it to achieve glycemic control targets for
      hospitalized patients with diabetes. METHODS: The MNT goals for hospitalized
      patients with diabetics are reviewed, and suggestions are made for attaining
      these goals. Emphasis is placed on the importance of proper screening and
      referral of inpatients to MNT service and on the process of providing MNT in the
      hospital setting. RESULTS: Implementing MNT in the hospital can be challenging
      because of the differences in nutrient and medication requirements compared with
      the home setting. Individualization of MNT during hospitalization, along with
      intensive medical management, generally is required if patients with diabetes are
      to achieve blood glucose targets. Barriers that may impact an individual's
      nutrition status and subsequently affect glycemic control include poor appetite,
      inability to eat, increased nutrient and calorie needs due to catabolic stress,
      variation in diabetes medications, and the possible need for enteral or
      parenteral nutrition support. There is limited evidence on what constitutes the
      optimal diet for hospitalized patients with diabetes. The consistent carbohydrate
      meal-planning system has been recommended because carbohydrate intake is the
      primary nutritional influence on blood glucose; this system focuses on the total
      grams of carbohydrate as the key strategy to achieve blood glucose control.
      Introduction of the consistent carbohydrate system requires that all healthcare
      disciplines understand the rationale of the system; and for the system to be
      effective, coordination must exist between nursing and nutrition services.
      Established guidelines for integration of diabetes medications with meals,
      snacks, or nutrition support, developed by a multidisciplinary healthcare team,
      will help ensure that the nutrition care plan works together with the medical
      treatment plan. The key areas of focus to improve inpatient glycemic control are:
      establishing screening criteria for appropriate referral to a registered
      dietitian; identifying nutrition-related issues in clinical pathways and patient
      care plans; implementing and maintaining standardized diet orders such as
      consistent carbohydrate menus; integrating blood glucose monitoring results with
      nutrition care plans; using standing orders for diabetes education and diabetes
      MNT as appropriate; and standardizing discharge follow-up orders for MNT and
      diabetes education post-discharge when necessary.

PMID- 16905520
TI  - Promoting continuing education in diabetes management.
AB  - Diabetes knowledge among hospital nurses is suboptimal. Studies that measured
      basic diabetes knowledge among nurses in a variety of clinical settings have
      consistently reported poor understanding of hemoglobin A1C, medication usage and
      side effects, and self-care diabetes management. Although diabetes is a common
      diagnosis among hospitalized patients, many nurses report they have never
      attended an update on diabetes management. To promote advances in glycemic
      control within the hospital setting, the nursing staff must be better educated in
      the theoretical framework and clinical practice guidelines for diabetes
      management. The methods used to promote continuing education in diabetes among
      staff nurses need to be cost-effective as well as flexible to accommodate work
      shifts and learning needs. Because many hospitals are facing staff shortages and
      increased patient acuity, staff development needs may not be a high priority. To
      be successful, updating diabetes knowledge must be a collaborative effort
      involving clinical care, research, and education. Mentoring and peer support also
      are useful methods for improving glycemia in the hospital setting.

PMID- 16905521
TI  - No patient left behind: evaluation and design of intravenous insulin infusion
      algorithms.
AB  - OBJECTIVE: To define the characteristics of performance evaluation, algorithm
      design, and regulation of insulin delivery by which professionals and the
      healthcare system might differentiate between methodologies for intravenous
      insulin infusion. METHODS: Published performance criteria used in the assessment
      of intravenous insulin infusion algorithms are classified. The structure of
      intravenous insulin infusion formulae is reviewed, as are technologies that might
      lead to future improvement. RESULTS: Among published reports, no standardization
      was discernable for description of algorithm characteristics or performance.
      Except for time-to-target and hypoglycemic episodes, measures using the patient
      as unit of observation are not employed consistently. CONCLUSION: The healthcare
      system needs criteria for evaluation and minimal acceptable standards for
      assessing performance of any algorithm, decision support system, or closed-loop
      system for intravenous insulin infusion. Inclusion of patient-based measures is
      necessary to assess the ability of an algorithm to control variability between
      patients and within a given run. Standardization of performance reporting will
      help users to select appropriate methodologies.

PMID- 16905522
TI  - Memoirs of a root canal salesman: the successful implementation of a hospital
      wide intravenous insulin infusion protocol.
AB  - OBJECTIVE: To summarize key metabolic results from use of the Yale Insulin
      Infusion Protocols (IIPs), as well as the primary barriers to their
      implementation. To offer practical suggestions for overcoming these barriers,
      drawing from our experiences "selling root canals" during the successful
      implementation of our hospital-wide IIPs. METHODS: Since 2002, Yale IIPs have
      been employed to achieve strict glycemic control in our ICU patients. Barriers to
      protocol implementation were noted, and strategies were designed to overcome
      these barriers. RESULTS: In 2002, we implemented Version 1 of the Yale IIP, which
      purposefully targeted conservative blood glucose (BG) levels of 100 to 139 mg/dL.
      Following extensive hospital-wide experience with Version 1, Version 2 of the IIP
      (which debuted in 2004) successfully lowered BG targets to 90 to 119 mg/dL, with
      minimal impact on observed rates of hypoglycemia. These nurse-driven protocols
      safely and effectively controlled glucose levels in our ICU patients, without the
      need for ongoing physician supervision. CONCLUSION: This work describes the
      successful implementation of an evolving hospital-wide IIP. To be successful, an
      IIP must account for the following essential elements: (1) the current BG level,
      (2) the velocity of glycemic change, and (3) the current insulin infusion rate.
      We have reviewed five "points of emphasis" to consider when implementing an IIP.

PMID- 16905523
TI  - Insulin management of diabetic patients on general medical and surgical floors.
AB  - OBJECTIVE: To review the standardized subcutaneous insulin protocols for diabetic
      patients on general medical and surgical floors at the University of Vermont.
      METHOD: Insulin protocols were developed for inpatients eating regular meals, and
      those receiving continuous tube feedings or total parental nutrition. RESULTS:
      The recommended starting subcutaneous insulin protocol for patients receiving
      meals is a basal-bolus approach using 0.5 U/kg basal insulin (glargine once
      daily, or neutral protamine Hagedorn [NPH] twice daily) and 0.1 U/kg rapid analog
      at each meal (lispro, aspart, or glulisine) for the average patient. The dose of
      basal is lowered by 0.2 U/kg for medical conditions with a high sensitivity to
      insulin or that have an added risk for hypoglycemia (renal or hepatic impairment,
      thin or normal weight, elderly, frail, hypothyroidism, adrenal insuffi ciency,
      etc.). Alternatively, an extra 0.2 U/kg basal is given for states of presumed
      high insulin resistance such as marked obesity with metabolic syndrome, open
      wounds, infections, etc. In turn, patients receiving continuous tube feedings
      receive the same 24-hour insulin doses (0.6-1.0 U/kg) in divided doses of
      premixed 70/30 (NPH/regular) insulin every 8 hours. This program allows lowering
      or eliminating 1 of the doses for the increasingly common tube-feeding programs
      in rehabilitation centers or patients' homes that entail discontinuation of tube
      feeding for 6 to 8 hours. A variation on this approach is used with total
      parenteral nutrition (TPN), with a portion of the insulin placed in the TPN bag
      and the remainder given as "q 8 hour 70/30" insulin. Starting insulin doses for
      all of the programs are adjusted daily to attain inpatient blood glucose goals of
      <110 mg/dL fasting and 110 to 180 mg/dL throughout the day. CONCLUSION:
      Standardized protocols have been developed and implemented at the University of
      Vermont for patients receiving regular meals and continuous tube feedings or TPN.

PMID- 16905524
TI  - Evolution of a diabetes inpatient safety committee.
AB  - OBJECTIVE: To develop a multidisciplinary team, the Diabetes Inpatient Safety
      Committee (DPSC), to effectively address the many barriers to achieving glycemic
      control in the inpatient setting. METHODS: The development, implementation, and
      successes of the DPSC are described. RESULTS: By focusing on prevention of severe
      hypoglycemia, the DPSC identified and addressed areas related to inpatient
      management that contributed to uncontrolled glucose levels. The introduction of a
      hypoglycemia treatment protocol was followed by the development of a standardized
      order set for use of sliding scale insulin, with the eventual introduction of an
      Insulin Order Set guiding the use of scheduled and correctional insulin.
      Protocols and guidelines addressing more specific areas of inpatient glycemic
      management (insulin pump therapy, perioperative management, diabetic
      ketoacidosis, intravenous insulin) also have been developed. CONCLUSION: The
      successes of the DPSC to date have been directly related to strong institutional
      support, the dedication of a multidisciplinary team to address specific areas of
      glycemic management, the programmed introduction of order sets in conjunction
      with structured educational programs that accompany each protocol, and the use of
      quality improvement measures to evaluate the safety and efficacy of these
      protocols. Effective committees such as this will be instrumental in preventing
      errors and maximizing euglycemia.

PMID- 16905525
TI  - Tools, technologies, and informatics: supporting glycemic control.
AB  - OBJECTIVE: To overcome the challenges involved in the adoption and implementation
      of standards of glycemic control in the inpatient setting. METHODS: Three major
      barriers to effective glycemic control are examined, and solutions are discussed.
      RESULTS: The diabetes care process occurs at several levels of the hospital
      system, including the community level. Each level must be considered when
      solutions for glycemic control are determined and implementation planned.
      Workflow coordination is another challenge; it addresses the end users who
      provide patient care and use information support. Informatics, or the application
      of information technology to healthcare, can facilitate system-level and workflow
      integration efforts to improve glycemic control. CONCLUSION: Glycemic control can
      be achieved through coordinated and facilitated efforts at each level of the
      hospital system--individual, unit, and hospital-wide. Multidisciplinary team
      coordination, workflow integration, effective information sharing, and
      communication are required.

PMID- 16905526
TI  - Newly diagnosed diabetes/hyperglycemia in hospitals: what should we do?
AB  - OBJECTIVE: To examine the clinical problem of newly diagnosed
      diabetes/hyperglycemia in hospitals, and to develop a management strategy.
      METHODS: A review of the literature on outcomes and management of such patients.
      RESULTS: There are very few published papers on this subject, the majority being
      in patients with cardiovascular disease. However, there is recognition that the
      problem is common. No randomized clinic trials have been carried out on
      therapeutic strategies in such patients. The limited data available suggest that
      patients with newly diagnosed diabetes and hyperglycemia tend to have a poor
      prognosis. CONCLUSION: Newly diagnosed diabetes/hyperglycemia in hospital is a
      common problem and is associated with a poor prognosis. Therefore, it seems
      appropriate that such patients be managed the same way as patients with
      established diabetes. Following discharge, appropriate diagnostic testing is
      needed to establish the presence or absence of diabetes so that long-term
      treatment plans can be initiated.

PMID- 16905527
TI  - Phylogenetic background and carriage of pathogenicity island-like domains in
      relation to antibiotic resistance profiles among Escherichia coli urosepsis
      isolates.
AB  - We studied 100 well-characterized E. coli blood isolates from patients with
      urosepsis for their susceptibility to nalidixic acid, ampicillin and trimethoprim
      sulfamethoxazole, according to prevalence of virulence factors, phylogenetic
      groups and subgroups, PAI II(J96)-like domains (determined by physical linkage of
      cnf1, hly and hra) and PAI I(CFT073)-like domains (determined by physical linkage
      of papGII to the hly locus). Nalidixic acid resistance was associated with a
      lower prevalence of sfa/foc, K1 antigen, pathogenicity island II(J96)-like
      domains, subgroup B2/I and a shift towards group A.

PMID- 16905528
TI  - Comparison of three standardized disc susceptibility testing methods for
      colistin.
AB  - OBJECTIVES: With increasing antibiotic resistance in Gram-negative bacteria, the
      use of the polymyxins has increased in recent years. Antibiotic disc
      susceptibility testing remains the most widely used method in clinical
      laboratories, but there is very little data on the accuracy of disc testing
      methods for colistin. In this study, the accuracy of three standardized methods
      of disc susceptibility testing for colistin was compared with agar dilution.
      METHODS: A total of 228 clinical isolates of Acinetobacter spp., Pseudomonas
      aeruginosa and Enterobacteriaceae were included in the study. Isolates were
      tested by agar dilution for susceptibility to colistin, and results were compared
      with those obtained by three disc susceptibility testing methods (product insert
      based on CLSI methodology, British BSAC and French SFM). RESULTS: Colistin
      displayed good activity against Acinetobacter spp., Klebsiella spp. and
      Escherichia coli (MIC(90) 2 mg/L) but was less active against P. aeruginosa
      (MIC(90) 4 mg/L) and Enterobacter spp. (MIC(90) >or= 128 mg/L). Totally, 81%, 79%
      and 89% of colistin-resistant isolates were falsely reported as susceptible when
      tested by the product insert, BSAC and SFM testing methods, respectively. There
      were no false-resistant results. CONCLUSIONS: Disc susceptibility testing methods
      are unreliable at detecting colistin resistance. Dilution methods should be the
      method of choice for susceptibility testing of colistin.

PMID- 16905529
TI  - In vitro activity of linezolid against clinical isolates of Fusobacterium spp.
AB  - OBJECTIVES: Although most susceptibility studies for linezolid have investigated
      aerobic bacteria, only a few have investigated anaerobe isolates. The aim of the
      present study was to determine the antibacterial activity of linezolid against a
      larger sample of clinical isolates of Fusobacterium spp. and to report on the
      detailed susceptibility, stratified by species. METHODS: The in vitro
      susceptibility of 80 clinical isolates of Fusobacterium (Fusobacterium
      necrophorum, n = 34; Fusobacterium nucleatum, n = 20; Fusobacterium varium, n =
      18; Fusobacterium mortiferum; n = 8) was tested and compared with the activity of
      the older compounds amoxicillin and amoxicillin/clavulanic acid. RESULTS: The MIC
      of linezolid ranged from 0.016 to 1.0 mg/L, with the MIC(90) being 0.5 mg/L. The
      highest MIC obtained for linezolid (1.0 mg/L) was measured for an F. varium
      isolate. The MIC(90) for both, amoxicillin (range: 0.016-0.75 mg/L) and
      amoxicillin/clavulanic acid (range: 0.047-0.75 mg/L), was 0.5 mg/L. Overall, no
      resistant strains were found in the study. CONCLUSIONS: Compared with amoxicillin
      and amoxicillin/clavulanic acid, linezolid was less active against F. necrophorum
      (MIC(90) 0.25 mg/L) and F. nucleatum (MIC(90) 0.25 mg/L), equally active against
      F. varium (MIC(90) 0.75 mg/L) and slightly more active against F. mortiferum
      (MIC(90) 0.19 mg/L).

PMID- 16905530
TI  - Mechanisms in eukaryotic mismatch repair.

PMID- 16905531
TI  - Conus peptides: biodiversity-based discovery and exogenomics.

PMID- 16905532
TI  - Proteins in the Neurospora circadian clockworks.

PMID- 16905533
TI  - Phosphorylation and up-regulation of diacylglycerol kinase gamma via its
      interaction with protein kinase C gamma.
AB  - Diacylglycerol (DAG) acts as an allosteric activator of protein kinase C (PKC)
      and is converted to phosphatidic acid by DAG kinase (DGK). Therefore, DGK is
      thought to be a negative regulator of PKC activation. Here we show molecular
      mechanisms of functional coupling of the two kinases. gammaPKC directly
      associated with DGKgamma through its accessory domain (AD), depending on Ca2+ as
      well as phosphatidylserine/diolein in vitro. Mass spectrometric analysis and
      mutation studies revealed that gammaPKC phosphorylated Ser-776 and Ser-779 in the
      AD of DGKgamma. The phosphorylation by gammaPKC resulted in activation of
      DGKgamma because a DGKgamma mutant in which Ser-776 and Ser-779 were substituted
      with glutamic acid to mimic phosphorylation exhibited significantly higher
      activity compared with wild type DGKgamma and an unphosphorylatable DGKgamma
      mutant. Importantly, the interaction of the two kinases and the phosphorylation
      of DGKgamma by gammaPKC could be confirmed in vivo, and overexpression of the AD
      of DGKgamma inhibited re-translocation of gammaPKC. These results demonstrate
      that localization and activation of the functionally correlated kinases, gammaPKC
      and DGKgamma, are spatio-temporally orchestrated by their direct association and
      phosphorylation, contributing to subtype-specific regulation of DGKgamma and DAG
      signaling.

PMID- 16905534
TI  - Phosphorylation of SHP-2 regulates interactions between the endoplasmic reticulum
      and focal adhesions to restrict interleukin-1-induced Ca2+ signaling.
AB  - Interleukin-1 (IL-1)-induced Ca2+ signaling in fibroblasts is constrained by
      focal adhesions. This process involves the proteintyrosine phosphatase SHP-2,
      which is critical for IL-1-induced phosphorylation of phospholipase Cgamma1,
      thereby enhancing IL-1-induced Ca2+ release and ERK activation. Currently, the
      mechanisms by which SHP-2 modulates Ca2+ release from the endoplasmic reticulum
      are not defined. We used immunoprecipitation and fluorescence protein-tagged SHP
      2 or endoplasmic reticulum (ER)-protein expression vectors, and an ER-specific
      calcium indicator, to examine the functional relationships between SHP-2, focal
      adhesions, and IL-1-induced Ca2+ release from the ER. By total internal
      reflection fluorescence microscopy to image subplasma membrane compartments, SHP
      2 co-localized with the ER-associated proteins calnexin and calreticulin at sites
      of focal adhesion formation in fibroblasts. IL-1beta promoted time-dependent
      recruitment of SHP-2 and ER proteins to focal adhesions; this process was blocked
      in cells treated with small interfering RNA for SHP-2 and in cells expressing a
      Y542F SHP-2 mutant. IL-1 stimulated inositol 1,4,5-trisphosphate receptor
      mediated Ca2+ release from the ER subjacent to the plasma membrane that was
      tightly localized around fibronectin-coated beads and was reduced 4-fold in cells
      expressing Tyr-542 SHP-2 mutant. In subcellular fractions enriched for ER
      proteins, immunoprecipitation demonstrated that IL-1-enhanced association of SHP
      2 with the type 1 inositol 1,4,5-trisphosphate receptor was dependent on Tyr-542
      of SHP-2. We conclude that Tyr-542 of SHP-2 modulates IL-1-induced Ca2+ signals
      and association of the ER with focal adhesions.

PMID- 16905535
TI  - Control of Listeria superoxide dismutase by phosphorylation.
AB  - Superoxide dismutases (SODs) are enzymes that protect organisms against
      superoxides and reactive oxygen species (ROS) produced during their active
      metabolism. ROS are major mediators of phagocytes microbicidal activity. Here we
      show that the cytoplasmic Listeria monocytogenes MnSOD is phosphorylated on
      serine and threonine residues and less active when bacteria reach the stationary
      phase. We also provide evidence that the most active nonphosphorylated form of
      MnSOD can be secreted via the SecA2 pathway in culture supernatants and in
      infected cells, where it becomes phosphorylated. A Deltasod deletion mutant is
      impaired in survival within macrophages and is dramatically attenuated in mice.
      Together, our results demonstrate that the capacity to counteract ROS is an
      essential component of L. monocytogenes virulence. This is the first example of a
      bacterial SOD post-translationally controlled by phosphorylation, suggesting a
      possible new host innate mechanism to counteract a virulence factor.

PMID- 16905536
TI  - Spectral and kinetic equivalence of oxidized cytochrome C oxidase as isolated and
      "activated" by reoxidation.
AB  - The spectral and kinetic characteristics of two oxidized states of bovine heart
      cytochrome c oxidase (CcO) have been compared. The first is the oxidized state of
      enzyme isolated in the fast form (O) and the second is the form that is obtained
      immediately after oxidation of fully reduced CcO with O2 (OH). No observable
      differences were found between O and OH states in: (i) the rate of anaerobic
      reduction of heme a3 for both the detergent-solubilized enzyme and for enzyme
      embedded in its natural membraneous environment, (ii) the one-electron
      distribution between heme a3 and CuB in the course of the full anaerobic
      reduction, (iii) the optical and (iv) EPR spectra. Within experimental error of
      these characteristics both forms are identical. Based on these observations it is
      concluded that the reduction potentials and the ligation states of heme a3 and
      CuB are the same for CcO in the O and OH states.

PMID- 16905537
TI  - The bacterial signal molecule, ppGpp, mediates the environmental regulation of
      both the invasion and intracellular virulence gene programs of Salmonella.
AB  - During infection of mammalian hosts, facultative intracellular pathogens have to
      adjust rapidly to different environmental conditions encountered during passage
      through the gastrointestinal tract and following uptake into epithelial cells and
      macrophages. Successful establishment within the host therefore requires the
      coordinated expression of a large number of virulence genes necessary for the
      adaptation between the extracellular and intracellular phases of infection. In
      this study we show that the bacterial signal molecule, ppGpp, plays a major role
      in mediating the environmental signals involved in the regulation of both the
      extracellular and intracellular virulence gene programs. Under oxygen limiting
      conditions, we observed a strong ppGpp dependence for invasion gene expression,
      the result of severe reductions in expression of the Salmonella pathogenicity
      island (SPI) 1 transcriptional regulator genes hilA, C, and D and invF.
      Overexpression of the non-SPI1-encoded regulator RtsA restored hilA expression in
      the absence of ppGpp. SPI2-encoded genes, required for intracellular
      proliferation in macrophages, were activated in the wild type strain under
      aerobic, late log phase growth conditions. The expression of SPI2 genes was also
      shown to be ppGpp-dependent under these conditions. The results from this study
      suggest a mechanism for the alternate regulation of the opposing extracellular
      and intracellular virulence gene programs and indicate a remarkable specificity
      for ppGpp in the regulation of genes involved in virulence compared with the rest
      of the genome. This is the first demonstration that this highly conserved
      regulatory system is involved in bacterial virulence gene expression on a global
      scale.

PMID- 16905538
TI  - Cilia-like structures and polycystin-1 in osteoblasts/osteocytes and associated
      abnormalities in skeletogenesis and Runx2 expression.
AB  - We examined the osteoblast/osteocyte expression and function of polycystin-1
      (PC1), a transmembrane protein that is a component of the polycystin-2 (PC2)
      ciliary mechano-sensor complex in renal epithelial cells. We found that MC3T3-E1
      osteoblasts and MLO-Y4 osteocytes express transcripts for PC1, PC2, and the
      ciliary proteins Tg737 and Kif3a. Immunohistochemical analysis detected cilia
      like structures in MC3T3-E1 osteoblastic and MLO-Y4 osteocyte-like cell lines as
      well as primary osteocytes and osteoblasts from calvaria. Pkd1m1Bei mice have
      inactivating missense mutations of Pkd1 gene that encode PC1. Pkd1m1Bei
      homozygous mutant mice demonstrated delayed endochondral and intramembranous bone
      formation, whereas heterozygous Pkd1m1Bei mutant mice had osteopenia caused by
      reduced osteoblastic function. Heterozygous and homozygous Pkd1m1Bei mutant mice
      displayed a gene dose-dependent decrease in the expression of Runx2 and
      osteoblast-related genes. In addition, overexpression of constitutively active
      PC1 C-terminal constructs in MC3T3-E1 osteoblasts resulted in an increase in
      Runx2 P1 promoter activity and endogenous Runx2 expression as well as an increase
      in osteoblast differentiation markers. Conversely, osteoblasts derived from
      Pkd1m1Bei homozygous mutant mice had significant reductions in endogenous Runx2
      expression, osteoblastic markers, and differentiation capacity ex vivo. Co
      expression of constitutively active PC1 C-terminal construct into Pkd1m1Bei
      homozygous osteoblasts was sufficient to normalize Runx2 P1 promoter activity.
      These findings are consistent with a possible functional role of cilia and PC1 in
      anabolic signaling in osteoblasts/osteocytes.

PMID- 16905539
TI  - Structural and functional analysis of a conjugated bile salt hydrolase from
      Bifidobacterium longum reveals an evolutionary relationship with penicillin V
      acylase.
AB  - Bile salt hydrolase (BSH) is an enzyme produced by the intestinal microflora that
      catalyzes the deconjugation of glycine- or taurine-linked bile salts. The crystal
      structure of BSH reported here from Bifidobacterium longum reveals that it is a
      member of N-terminal nucleophil hydrolase structural superfamily possessing the
      characteristic alphabetabetaalpha tetra-lamellar tertiary structure arrangement.
      Site-directed mutagenesis of the catalytic nucleophil residue, however, shows
      that it has no role in zymogen processing into its corresponding active form.
      Substrate specificity was studied using Michaelis-Menten and inhibition kinetics
      and fluorescence spectroscopy. These data were compared with the specificity
      profile of BSH from Clostridium perfrigens and pencillin V acylase from Bacillus
      sphaericus, for both of which the three-dimensional structures are available.
      Comparative analysis shows a gradation in activity toward common substrates,
      throwing light on a possible common route toward the evolution of pencillin V
      acylase and BSH.

PMID- 16905540
TI  - Oxygen tension regulates chondrocyte differentiation and function during
      endochondral ossification.
AB  - Cartilage functions at a lower oxygen tension than most other tissues. To
      determine the role of oxygen tension in chondrocyte differentiation and function,
      we investigated the influence of oxygen tension in the pluripotent mesenchymal
      cell line C3H10T1/2 and 14.5E mice embryo forelimb organ culture. 10T1/2 cells
      and embryo forelimbs were cultured under normoxia (20% O2) or hypoxia (5% O2) in
      the presence of recombinant human bone morphogenetic protein 2. To elucidate the
      mechanism by which oxygen tension influences chondrocyte differentiation, the
      Smad pathway was examined using Smad6 overexpression adenovirus and Smad6
      transgenic mice embryo forelimbs. The p38 MAPK pathway was examined using
      dominant-negative MKK3 and FR167653, a specific p38 MAPK inhibitor. The
      transcriptional activities of Sox9 and Runx2 were also investigated. Hypoxia
      promoted bone morphogenetic protein 2-induced glycosaminoglycan production and
      suppressed alkaline phosphatase activity and mineralization of C3H10T1/2. Thus,
      hypoxia promoted chondrocytic commitment rather than osteoblastic
      differentiation. In the mice embryo forelimb organ culture, hypoxia increased
      cartilaginous matrix synthesis. These effects were primarily mediated by p38 MAPK
      activation, independent of Sox9. Hypoxia inhibited Col10a1 (type X collagen
      alpha1) expression via down-regulation of Runx2 activity by Smad suppression and
      histone deacetylase 4 activation. In conclusion, hypoxia promotes chondrocytic
      differentiation and cartilage matrix synthesis and suppresses terminal
      chondrocyte differentiation. These hypoxia-induced phenomena may act on
      chondrocytes to enhance and preserve their phenotype and function during
      chondrocyte differentiation and endochondral ossification.

PMID- 16905541
TI  - MDMX overexpression prevents p53 activation by the MDM2 inhibitor Nutlin.
AB  - The p53 tumor suppressor plays a key role in maintaining genomic stability and
      protection against malignant transformation. MDM2 and MDMX are both p53-binding
      proteins that regulate p53 stability and activity. Recent development of the MDM2
      inhibitor Nutlin 3 has greatly facilitated functional analysis of MDM2-p53
      binding. We found that although MDMX is homologous to MDM2 and binds to the same
      region on p53 N terminus, Nutlin does not disrupt p53-MDMX interaction. The
      ability of Nutlin to activate p53 is compromised in tumor cells overexpressing
      MDMX. Combination of Nutlin with MDMX siRNA resulted in synergistic activation of
      p53 and growth arrest. These results suggest that MDMX is also a valid target for
      p53 activation in tumor cells. Development of novel compounds that are MDMX
      specific or optimized for dual-inhibition of MDM2 and MDMX are necessary to
      achieve full activation of p53 in tumor cells.

PMID- 16905542
TI  - The multigenic sphingomyelin synthase family.

PMID- 16905543
TI  - Dichotomic phylogenetic tree of the pyruvate kinase family: K+ -dependent and 
      independent enzymes.
AB  - K+ dependence was assumed to be a feature of all pyruvate kinases until it was
      discovered that some enzymes express K+ -independent activity. Almost all the K+ 
      independent pyruvate kinases have Lys at position 117, instead of the Glu present
      in the K+ -dependent muscle enzyme. Mutagenesis studies show that the internal
      positive charge substitutes for the K+ requirement (Laughlin, L. T. & Reed, G. H.
      (1997) Arch. Biochem. Biophys. 348, 262-267). In this work a phylogenetic
      analysis of pyruvate kinase was performed to ascertain the abundance of K+ 
      independent activities and to explore whether the K+ activating effect is related
      to the evolutionary history of the enzyme. Of the 230 studied sequences, 46% have
      Lys at position 117, and the rest have Glu. Pyruvate kinases with Lys117 and
      Glu117 are separated in two clusters. All of the enzymes of the Glu117 cluster
      that have been characterized are K+ -dependent, whereas those of the Lys117
      cluster are K+ -independent. Thus, there is a strict correlation between the
      dichotomy of the tree and the dependence of activity on K+. 77% of the pyruvate
      kinases that possess Lys117 have Lys113/Gln114; they also have Ile, Val, or Leu
      at position 120. These residues are replaced by Glu117 and Thr113/Lys114/Thr120
      in 80% of K+ -dependent pyruvate kinases. Structural analysis indicates that
      these residues are in a hinge region involved in the acquisition of the catalytic
      conformation of the enzyme. The route of conversion from K+ -independent to K+ 
      dependent pyruvate kinases is described. A plausible explanation of how enzymes
      developed K+ dependence is put forth.

PMID- 16905545
TI  - The first structure from the SOUL/HBP family of heme-binding proteins, murine
      P22HBP.
AB  - Murine p22HBP, a 22-kDa monomer originally identified as a cytosolic heme-binding
      protein ubiquitously expressed in various tissues, has 27% sequence identity to
      murine SOUL, a heme-binding hexamer specifically expressed in the retina. In
      contrast to murine SOUL, which binds one heme per subunit via coordination of the
      Fe(III)-heme to a histidine, murine p22HBP binds one heme molecule per subunit
      with no specific axial ligand coordination of the Fe(III)-heme. Using intrinsic
      protein fluorescence quenching, the values for the dissociation constants of
      p22HBP for hemin and protoporphyrin-IX were determined to be in the low nanomolar
      range. The three-dimensional structure of murine p22HBP, the first for a protein
      from the SOUL/HBP family, was determined by NMR methods to consist of a 9
      stranded distorted beta-barrel flanked by two long alpha-helices. Although
      homologous domains have been found in three bacterial proteins, two of which are
      transcription factors, the fold determined for p22HBP corresponds to a novel
      alpha plus beta fold in a eukaryotic protein. Chemical shift mapping localized
      the tetrapyrrole binding site to a hydrophobic cleft formed by residues from
      helix alphaA and an extended loop. In an attempt to assess the structural basis
      for tetrapyrrole binding in the SOUL/HBP family, models for the p22HBP
      protoporphyrin-IX complex and the SOUL protein were generated by manual docking
      and automated methods.

PMID- 16905544
TI  - TcR and TcR-CD28 engagement of protein kinase B (PKB/AKT) and glycogen synthase
      kinase-3 (GSK-3) operates independently of guanine nucleotide exchange factor VAV
      1.
AB  - TcRzeta/CD3 and TcRzeta/CD3-CD28 signaling requires the guanine nucleotide
      exchange factor (GEF) Vav-1 as well as the activation of phosphatidylinositol 3
      kinase, protein kinase B (PKB/AKT), and its inactivation of glycogen synthase
      kinase-3 (GSK-3). Whether these two pathways are connected or operate
      independently of each other in T-cells has been unclear. Here, we report that
      anti-CD3 and anti-CD3/CD28 can induce PKB and GSK-3alpha phosphorylation in the
      Vav-1(-/-) Jurkat cell line J. Vav.1 and in primary CD4-positive Vav-1(-/-) T
      cells. Reduced GSK-3alpha phosphorylation was observed in Vav-1,2,3(-/-) T-cells
      together with a complete loss of FOXO1 phosphorylation. Furthermore, PKB and GSK
      3 phosphorylation was unperturbed in the presence of GEF-inactive Vav-1 that
      inhibited interleukin-2 gene activation and a form of Src homology 2 domain
      containing lymphocytic protein of 76-kDa (SLP-76) that is defective in binding to
      Vav-1. The pathway also was intact under conditions of c-Jun N-terminal kinase
      (JNK) inhibition and disruption of the actin cytoskeleton by cytochalasin D. Both
      events are down-stream targets of Vav-1. Overall, our findings indicate that the
      TcR and TcR-CD28 driven PKB-GSK-3 pathway can operate independently of Vav-1 in T
      cells.

PMID- 16905546
TI  - NQO1 and NQO2 regulation of humoral immunity and autoimmunity.
AB  - NAD(P)H:quinone oxidoreductase 1 (NQO1) and NRH:quinone oxidoreductase 2 (NQO2)
      are cytosolic enzymes that catalyze metabolic reduction of quinones and
      derivatives. NQO1-null and NQO2-null mice were generated that showed decreased
      lymphocytes in peripheral blood, myeloid hyperplasia, and increased sensitivity
      to skin carcinogenesis. In this report, we investigated the in vivo role of NQO1
      and NQO2 in immune response and autoimmunity. Both NQO1-null and NQO2-null mice
      showed decreased B-cells in blood, lower germinal center response, altered B cell
      homing, and impaired primary and secondary immune responses. NQO1-null and NQO2
      null mice also showed susceptibility to autoimmune disease as revealed by
      decreased apoptosis in thymocytes and pre-disposition to collagen-induced
      arthritis. Further experiments showed accumulation of NADH and NRH, cofactors for
      NQO1 and NQO2, indicating altered intracellular redox status. The studies also
      demonstrated decreased expression and lack of activation of immune-related factor
      NF-kappaB. Microarray analysis showed altered chemokines and chemokine receptors.
      These results suggest that the loss of NQO1 and NQO2 leads to altered
      intracellular redox status, decreased expression and activation of NF-kappaB, and
      altered chemokines. The results led to the conclusion that NQO1 and NQO2 are
      endogenous factors in the regulation of immune response and autoimmunity.

PMID- 16905547
TI  - Structure and dynamics of ASC2, a pyrin domain-only protein that regulates
      inflammatory signaling.
AB  - Pyrin domain (PYD)-containing proteins are key components of pathways that
      regulate inflammation, apoptosis, and cytokine processing. Their importance is
      further evidenced by the consequences of mutations in these proteins that give
      rise to autoimmune and hyperinflammatory syndromes. PYDs, like other members of
      the death domain (DD) superfamily, are postulated to mediate homotypic
      interactions that assemble and regulate the activity of signaling complexes.
      However, PYDs are presently the least well characterized of all four DD
      subfamilies. Here we report the three-dimensional structure and dynamic
      properties of ASC2, a PYD-only protein that functions as a modulator of
      multidomain PYD-containing proteins involved in NF-kappaB and caspase-1
      activation. ASC2 adopts a six-helix bundle structure with a prominent loop,
      comprising 13 amino acid residues, between helices two and three. This loop
      represents a divergent feature of PYDs from other domains with the DD fold.
      Detailed analysis of backbone 15N NMR relaxation data using both the Lipari-Szabo
      model-free and reduced spectral density function formalisms revealed no evidence
      of contiguous stretches of polypeptide chain with dramatically increased internal
      motion, except at the extreme N and C termini. Some mobility in the fast,
      picosecond to nanosecond timescale, was seen in helix 3 and the preceding alpha2
      alpha3 loop, in stark contrast to the complete disorder seen in the corresponding
      region of the NALP1 PYD. Our results suggest that extensive conformational
      flexibility in helix 3 and the alpha2-alpha3 loop is not a general feature of
      pyrin domains. Further, a transition from complete disorder to order of the
      alpha2-alpha3 loop upon binding, as suggested for NALP1, is unlikely to be a
      common attribute of pyrin domain interactions.

PMID- 16905549
TI  - Defective Mre11-dependent activation of Chk2 by ataxia telangiectasia mutated in
      colorectal carcinoma cells in response to replication-dependent DNA double strand
      breaks.
AB  - The Mre11.Rad50.Nbs1 (MRN) complex binds DNA double strand breaks to repair DNA
      and activate checkpoints. We report MRN deficiency in three of seven colon
      carcinoma cell lines of the NCI Anticancer Drug Screen. To study the involvement
      of MRN in replication-mediated DNA double strand breaks, we examined checkpoint
      responses to camptothecin, which induces replication-mediated DNA double strand
      breaks after replication forks collide with topoisomerase I cleavage complexes.
      MRN-deficient cells were deficient for Chk2 activation, whereas Chk1 activation
      was independent of MRN. Chk2 activation was ataxia telangiectasia mutated (ATM)
      dependent and associated with phosphorylation of Mre11 and Nbs1. Mre11
      complementation in MRN-deficient HCT116 cells restored Chk2 activation as well as
      Rad50 and Nbs1 levels. Conversely, Mre11 down-regulation by small interference
      RNA (siRNA) in HT29 cells inhibited Chk2 activation and down-regulated Nbs1 and
      Rad50. Proteasome inhibition also restored Rad50 and Nbs1 levels in HCT116 cells
      suggesting that Mre11 stabilizes Rad50 and Nbs1. Chk2 activation was also
      defective in three of four MRN-proficient colorectal cell lines because of low
      Chk2 levels. Thus, six of seven colon carcinoma cell lines from the NCI
      Anticancer Drug Screen are functionally Chk2-deficient in response to replication
      mediated DNA double strand breaks. We propose that Mre11 stabilizes Nbs1 and
      Rad50 and that MRN activates Chk2 downstream from ATM in response to replication
      mediated DNA double strand breaks. Chk2 deficiency in HCT116 is associated with
      defective S-phase checkpoint, prolonged G2 arrest, and hypersensitivity to
      camptothecin. The high frequency of MRN and Chk2 deficiencies may contribute to
      genomic instability and therapeutic response to camptothecins in colorectal
      cancers.

PMID- 16905550
TI  - Twisted gastrulation modulates bone morphogenetic protein-induced collagen II and
      X expression in chondrocytes in vitro and in vivo.
AB  - Twisted gastrulation (TSG) is an extracellular modulator of bone morphogenetic
      protein (BMP) activity and regulates dorsoventral axis formation in early
      Drosophila and Xenopus development. Studies on tsg-deficient mice also indicated
      a role of this protein in skeletal growth, but the mechanism of TSG activity in
      this process has not yet been investigated. Here we show for the first time by in
      situ hybridization and immunohistochemistry that TSG is strongly expressed in
      bovine and mouse growth plate cartilage as well as in fetal ribs, vertebral
      cartilage, and cartilage anlagen of the skull. Furthermore we provide evidence
      that TSG is directly involved in BMP-regulated chondrocyte differentiation and
      maturation. In vitro, TSG impaired the dose-dependent BMP-2 stimulation of
      collagen II and X expression in cultures of MC615 chondrocytes and primary mouse
      chondrocytes. In the presence of chordin, a BMP antagonist, the inhibitory effect
      of TSG was further enhanced. TSG also inhibited BMP-2-stimulated phosphorylation
      of Smad factors in chondrocytes, confirming the role of TSG as a modulator of BMP
      signaling. For analysis of TSG functions in cartilage development in vivo, the
      gene was overexpressed in transgenic mice under the control of the cartilage
      specific Col2a1 promoter. As a result, Col10a1 expression was significantly
      reduced in the growth plates of transgenic embryos and newborns in comparison
      with wild type littermates as shown by in situ hybridization and by real time PCR
      analysis. The data suggest that TSG is an important modulator of BMP-regulated
      cartilage development and chondrocyte differentiation.

PMID- 16905548
TI  - Plasma protein beta-2-glycoprotein 1 mediates interaction between the anti-tumor
      monoclonal antibody 3G4 and anionic phospholipids on endothelial cells.
AB  - A promising target on tumor vasculature is phosphatidylserine (PS), an anionic
      phospholipid that resides exclusively on the inner leaflet of the plasma membrane
      of resting mammalian cells. We have shown previously that PS becomes exposed on
      the surface of endothelial cells (EC) in solid tumors. To target PS on tumor
      vasculature, the murine monoclonal antibody 3G4 was developed. 3G4 localizes to
      tumor vasculature, inhibits tumor growth, and enhances anti-tumor chemotherapies
      without toxicity in mice. A chimeric version of 3G4 is in clinical trials. In
      this study, we investigated the basis for the interaction between 3G4 and EC with
      surface-exposed PS. We demonstrate that antibody binding to PS is dependent on
      plasma protein beta-2-glycoprotein 1 (beta2GP1). beta2GP1 is a 50-kDa
      glycoprotein that binds weakly to anionic phospholipids under physiological
      conditions. We show that 3G4 enhances binding of beta2GP1 to EC induced to expose
      PS. We also show that divalent 3G4-beta2GP1 complexes are required for enhanced
      binding, since 3G4 Fab' fragments do not bind EC with exposed PS. Finally, we
      demonstrate that an artificial dimeric beta2GP1 construct binds to EC with
      exposed PS in the absence of 3G4, confirming that antibody binding is mediated by
      dimerization of beta2GP1. Together, these data indicate that 3G4 targets tumor EC
      by increasing the avidity of beta2GP1 for anionic phospholipids through formation
      of multivalent 3G4-beta2GP1 complexes.

PMID- 16905551
TI  - Marfan syndrome-causing mutations in fibrillin-1 result in gross morphological
      alterations and highlight the structural importance of the second hybrid domain.
AB  - Mutations in fibrillin-1 result in Marfan syndrome, which affects the
      cardiovascular, skeletal and ocular systems. The multiorgan involvement and wide
      spectrum of associated phenotypes highlights the complex pathogenesis underlying
      Marfan syndrome. To elucidate the genotype to phenotype correlations, we
      engineered four Marfan syndrome causing mutations into a fibrillin-1 fragment
      encoded by exons 18-25, a region known to interact with tropoelastin. Biophysical
      and biochemical approaches, including small angle x-ray scattering, analytical
      ultracentrifugation, and circular dichroism, were used to study the impact of
      these mutations upon the structure and function of the protein. Mutations G880S,
      C862R, and C908R, situated within the second hybrid domain, disrupted the ratio
      of alpha-helix to beta-sheet leading to a more compact conformation. These data
      clearly demonstrate the importance of the previously uncharacterized hybrid
      domain in fibrillin-1 structure. In contrast, mutation K1023N situated within the
      linker region between the third eight cysteine motif and cbEGF 11 markedly
      extended the length of the fragment. However, none of the mutations affected
      tropoelastin binding. The profound effects of all four mutations on fragment
      conformation suggest that they contribute to the pathogenesis of Marfan syndrome
      by disrupting protein folding and its assembly into fibrillin-rich microfibrils.

PMID- 16905552
TI  - The effectiveness of a tailored intervention for excessive alcohol consumption
      prior to elective surgery.
AB  - AIM: To assess the effectiveness of a tailored pre-operative intervention for
      excessive alcohol consumption in reducing post-operative complications and
      alcohol consumption thereafter. METHODS: Patients scheduled for elective surgery
      requiring at least overnight hospitalisation were screened for alcohol misuse.
      Consenting, eligible participants with > or =7 days to surgery at the time of
      screening were offered an intervention and those with <7 days to surgery were
      provided usual care. RESULTS: Over a period of 2 years and 10 months, 3139
      patients were screened to recruit 136 participants. Baseline analysis revealed a
      mean age of 53 (+/-15.8) years and a mean consumption of 71 g/day (+/-48.1). The
      intervention group (n = 45) did not differ significantly from controls (n = 91)
      in age, consumption, and number of current smokers, but there were significantly
      more women in the control group. There was no difference between the groups in
      major or minor complications experienced, or length of stay after controlling for
      age, gender, and baseline consumption. At 6-month follow-up there was a
      significant reduction in drinking for the entire study population. CONCLUSION:
      The study did not demonstrate any beneficial effect of the pre-operative
      intervention on post-operative complications. The relatively short time to
      surgery, intervention by a non-member of the surgical team, challenges to
      recruitment and reduced consumption in the control group may have limited the
      ability of the study to detect a significant effect of the intervention.

PMID- 16905553
TI  - Comparison of the fastest regenerating motor and sensory myelinated axons in the
      same peripheral nerve.
AB  - Functional outcome after peripheral nerve regeneration is often poor,
      particularly involving nerve injuries far from their targets. Comparison of
      sensory and motor axon regeneration before target reinnervation is not possible
      in the clinical setting, and previous experimental studies addressing the
      question of differences in growth rates of different nerve fibre populations led
      to conflicting results. We developed an animal model to compare growth and
      maturation of the fastest growing sensory and motor fibres within the same mixed
      nerve after Wallerian degeneration. Regeneration of cat tibial nerve after crush
      (n = 13) and section (n = 7) was monitored for up to 140 days, using implanted
      cuff electrodes placed around the sciatic and tibial nerves and wire electrodes
      at plantar muscles. To distinguish between sensory and motor fibres, recordings
      were carried out from L6-S2 spinal roots using cuff electrodes. The timing of
      laminectomy was based on the presence of regenerating fibres along the nerve
      within the tibial cuff. Stimulation of unlesioned tibial nerves (n = 6) evoked
      the largest motor response in S1 ventral root and the largest sensory response in
      L7 dorsal root. Growth rates were compared by mapping the regenerating nerve
      fibres within the tibial nerve cuff to all ventral or dorsal roots and,
      regardless of the lesion type, the fastest growth was similar in sensory and
      motor fibres. Maturation was assessed as recovery of the maximum motor and
      sensory conduction velocities (CVs) within the tibial nerve cuff. Throughout the
      observation period the CV was approximately 14% faster in regenerated sensory
      fibres than in motor fibres in accordance with the difference observed in control
      nerves. Recovery of amplitude was only partial after section, whereas the root
      distribution pattern was restored. Our data suggest that the fastest growth and
      maturation rates that can be achieved during regeneration are similar for motor
      and sensory myelinated fibres.

PMID- 16905554
TI  - Abnormal myocardial deformation properties in obese, non-hypertensive children:
      an ambulatory blood pressure monitoring, standard echocardiographic, and strain
      rate imaging study.
AB  - AIMS: The prevalence of obesity is increasing among children in the developed
      world. The association of obesity and abnormal cardiac function is still debated.
      The reported changes may reflect the role of comorbidities that contribute to
      ventricular dysfunction. Obese children, without arterial hypertension, may be a
      unique clinical opportunity to evaluate the effect of obesity, per se, on
      myocardial function, excluding the influence of possible comorbidities. We sought
      to define the preclinical effects of obesity on the cardiovascular system, of
      healthy children with excess weight who have no other clinically appreciable
      cause of heart disease, using the more sensitive ultrasonic-derived strain and
      strain rate (SR) imaging. METHODS AND RESULTS: We studied 300 subjects divided
      into two groups: (i) obese children (Group O: n=150; age, 12+/-3 years); (ii)
      healthy lean children comparable for age, sex, and pubertal stage (Referents:
      n=150; mean age, 12+/-3 years). Systolic (SBP) and diastolic blood pressure
      (DBP), as well as 24 h-SBP and 24 h-DBP were comparable between groups. Left
      ventricular (LV) mass/height(2.7) was increased (P<0.0001) in Group O (46+/-12
      g/m(2.7)) when compared with Referents (31+/-14 gm(2.7)). Standard
      echocardiographic indices of global systolic function were similar in the two
      groups. Intima-media thickness measured at the common carotid artery was not
      significantly different (P=0.4) in obese children (0.46+/-0.09 mm) when compared
      with Referents (0.45+/-0.07 mm). Obese children showed regional longitudinal peak
      systolic myocardial deformation properties (SR=-1.4+/-0.7 s(-1)) lower (P<0.0001)
      than those of Referents (SR=-2.2+/-0.5) in both left and right ventricle. In
      multivariable analysis, average peak systolic SR was significantly correlated
      with homeostasis model assessment of insulin resistance (P<0.01; coefficient,
      0.02; SE, 0.011), and insulin serum concentration (P<0.01; coefficient, 0.05; SE,
      0.023). Average LV peak systolic strain was significantly correlated with body
      mass index (P=0.0001; coefficient, 0.06; SE, 0.016), LVM/H(2.7) (P=0.006;
      coefficient, 0.016; SE, 0.018). CONCLUSIONS: Our study demonstrated that obesity,
      in absence of hypertension, is associated with significant reduction in systolic
      myocardial deformation properties already in childhood involving both right and
      left ventricle. Obesity not only is a risk factor for later cardiovascular
      disease, but also is associated with contemporaneous and significant impairment
      of longitudinal myocardial deformation properties.

PMID- 16905555
TI  - Should angiotensin-converting enzyme-inhibitors be used to improve outcome in
      patients with coronary artery disease and 'preserved' left ventricular function?
AB  - Early clinical studies investigating the role of angiotensin-converting enzyme
      (ACE) inhibitors in the treatment of heart failure unexpectedly demonstrated a
      possible reduction in coronary heart disease endpoints. Two large scale clinical
      trials, HOPE and EUROPA, both studies in patients with coronary artery disease
      (CAD) but without clinical evidence of heart failure, showed a highly significant
      improvement in coronary heart disease outcomes on treatment with ramipril and
      perindopril, respectively, in contrast, in a similar population, PEACE was unable
      to demonstrate such benefit with trandolapril. Meta-analyses of all trials
      involving ACE-inhibitors showed a highly significant improvement in coronary
      heart disease endpoints. Current ESC guidelines recommend ACE-inhibitor therapy
      in CAD patients with co-existing indications for ACE-inhibitors, such as
      hypertension, heart failure, left ventricular dysfunction, prior MI was left
      ventricular dysfunction, or diabetes (class I, level of evidence A). These
      guidelines also recommend ACE-inhibitor therapy in all patients with angina and
      proven coronary disease (class IIa, level of evidence B). However, in angina
      patients without independent indication for ACE-inhibitor treatment, the
      anticipated benefit should be weighted against the costs and risks of side
      effects; in these patients, only agents and doses of proven efficacy for
      secondary prevention should be employed.

PMID- 16905556
TI  - Aberrant cortical synaptic plasticity and dopaminergic dysfunction in a mouse
      model of Huntington's disease.
AB  - Predictive genetic testing for Huntington's disease (HD) has revealed early
      cognitive deficits in asymptomatic gene carriers, such as altered working memory,
      executive function and impaired recognition memory. The perirhinal cortex
      processes aspects of recognition memory and the underlying mechanism is believed
      to be long-term depression (LTD) of excitatory neurotransmission, the converse of
      long-term potentiation (LTP). We have used the R6/1 mouse model of HD to assess
      synaptic plasticity in the perirhinal cortex. We report here a progressive
      derailment of both LTD and short-term plasticity at perirhinal synapses. Layer
      II/III neurones gradually lose their ability to support LTD, show early nuclear
      localization of mutant huntingtin and display a progressive loss of membrane
      integrity (depolarization and loss of cell capacitance) accompanied by a
      reduction in the expression of D1 and D2 dopamine receptors visualized in layer I
      of the perirhinal cortex. Importantly, abnormalities in both short-term and long
      term plasticity can be reversed by the introduction of a D2 dopamine receptor
      agonist (Quinpirole), suggesting that alterations in dopaminergic signalling may
      underlie early cognitive dysfunction in HD.

PMID- 16905557
TI  - Evidence for involvement of the vitamin D receptor gene in idiopathic short
      stature via a genome-wide linkage study and subsequent association studies.
AB  - Stature is a highly heritable trait under both polygenic and major gene control.
      We aimed to identify genetic regions linked to idiopathic short stature (ISS) in
      childhood, through a whole genome scan in 92 families each with two affected
      children with ISS, including constitutional delay of growth and puberty and
      familial short stature. Linkage analysis was performed for ISS, height and bone
      age retardation. Chromosome 12q11 showed significant evidence of linkage to ISS
      and height (maximum non-parametric multipoint LOD scores 3.18 and 2.31 at 55-58
      cM, between D12S1301 and D12S1048), especially in sister-sister pairs (LOD score
      of 1.9 for ISS in 22 pairs). These traits were also linked to chromosomes 1q12
      and 2q36. The region on chromosome 12q11 had previously shown significant linkage
      to adult stature in several genome scans and harbors the vitamin D receptor gene,
      which has been associated with variation in height. A single nucleotide
      polymorphism (SNP) (rs10735810, FokI), which leads to a functionally relevant
      alteration at the protein level, showed preferential transmission of the
      transcriptionally more active G-allele to affected children (P=0.04) and seems to
      be responsible for the observed linkage (P=0.05, GIST test). Bone age retardation
      showed moderate linkage to chromosomes 19p11-q11 and 7p14 (LOD scores 1.69 at 57
      cM and 1.42 at 50 cM), but there was no clear overlap with linkage regions for
      stature. In conclusion, we identified significant linkage, which might be due to
      a functional SNP in the vitamin D receptor (VDR) gene and could be responsible
      for up to 34% of ISS cases in the population.

PMID- 16905558
TI  - Systematic review and meta-analysis of the association between complement factor
      H Y402H polymorphisms and age-related macular degeneration.
AB  - Age-related macular degeneration (AMD) is the leading cause of blindness in the
      developed world and complement factor H (CFH) polymorphism has been found to
      associated with the AMD. We performed a meta-analysis to estimate the magnitude
      of the gene effect and the possible mode of action. A meta-analysis of eight
      studies assessing association between the CFH Y402H polymorphism and AMD was
      performed. Data extraction and study quality assessment were performed in
      duplicate, and heterogeneity and publication bias were explored. There was strong
      evidence for association between CFH and AMD, with those having CC and TC
      genotypes being roughly six and 2.5 times more likely to have AMD than patients
      with TT genotype, suggesting a co-dominant, multiplicative genetic model. The
      population attributable risk for the CC/TC genotype is 58.9%, i.e. the CFH
      polymorphism is involved in over half of all AMD. This meta-analysis summarizes
      the strong evidence for an association between CFH and AMD and indicates a
      multiplicative model with each C allele increasing the odds of AMD by
      approximately 2.5-fold. This result is at least as important at the population
      level as ApoE4 and Alzheimer's disease, playing a role in almost 60% of AMD at
      the population level.

PMID- 16905559
TI  - Expression of the Rho-GEF Pbl/ECT2 is regulated by the UBE3A E3 ubiquitin ligase.
AB  - We applied genetic tools available in Drosophila to identify candidate substrates
      of the UBE3A ubiquitin ligase, the gene responsible for Angelman syndrome (AS).
      Human UBE3A was expressed in Drosophila heads to identify proteins differentially
      regulated in UBE3A-expressing versus wild-type extracts. Using two-dimensional
      gel and MALDI-TOF analysis, we detected 20 proteins that were differentially
      regulated by over-expression of human UBE3A in Drosophila heads. One protein
      responsive to UBE3A was the Rho-GEF pebble (pbl). Here, we present three lines of
      evidence suggesting that UBE3A regulates Pbl. First, we show genetic evidence
      that UBE3A and the Drosophila de-ubiquitinase fat facets (faf) exert opposing
      effects on Pbl function. Secondly, we find that both Pbl and ECT2, the mammalian
      orthologue of Pbl called epithelial cell transforming sequence 2 oncogene,
      physically interact with their respective ubiquitin E3 ligases. Finally, we show
      that Ect2 expression is regulated by Ube3a in mouse neurons as the pattern of
      Ect2 expression is dramatically altered in the hippocampus and cerebellum of
      Ube3a null mice. These results suggest that an orthologous UBE3A post
      translational regulatory pathway regulates neuronal outgrowth in the mammalian
      brain and that dysregulation of this pathway may result in neurological
      phenotypes including AS and possibly other autism spectrum disorders.

PMID- 16905560
TI  - RGS4 mRNA expression in postmortem human cortex is associated with COMT Val158Met
      genotype and COMT enzyme activity.
AB  - Linkage, association and postmortem studies have implicated regulator of G
      protein signaling 4 (RGS4), which negatively modulates signal transduction at G
      protein-coupled receptors, as a candidate schizophrenia susceptibility gene. We
      compared RGS4 mRNA expression in the dorsolateral prefrontal cortex (DLPFC),
      between normal controls and patients with schizophrenia in two independent
      cohorts (>100 subjects each) (the CBDB/NIMH Collection and the Stanley Array
      Collection), and in the hippocampus in the CBDB/NIMH Collection. We also examined
      the effects of the four previously identified putative RGS4 risk SNPs
      (rs10917670, rs951436, rs951439, rs2661319) on RGS4 expression levels in these
      cohorts. As dopamine signaling is linked to RGS4 expression and there is evidence
      for statistical epistasis between COMT Val158Met polymorphism and RGS4 alleles,
      we also examined relationships between the COMT Val158Met genotype and RGS4
      expression in the DLPFC. We did not detect a difference in RGS4 expression levels
      between schizophrenic patients (or bipolar disorder patients in the Stanley
      Collection) and controls and found no significant association between any of the
      RGS4 risk SNPs and RGS4 expression. However, COMT Val158Met genotype was
      associated with prefrontal and hippocampal RGS4 mRNA expression in an allele dose
      dependent manner, with carriers of the COMT Val allele showing significantly
      lower expression than heterozygous individuals or subjects homozygous for the Met
      allele. Consistent with these genotype effects, RGS4 mRNA was inversely
      correlated with the COMT enzyme activity in the DLPFC. These data suggest that
      RGS4 mRNA expression is associated with cortical dopamine signaling and
      illustrate the importance of genetic and/or environmental background in gene
      expression studies in schizophrenia.

PMID- 16905561
TI  - Heterogeneity at the HLA-DRB1 locus and risk for multiple sclerosis.
AB  - Variation in major histocompatibility complex genes on chromosome 6p21.3,
      specifically the human leukocyte antigen HLA-DR2 or DRB1*1501-DQB1*0602 extended
      haplotype, confers risk for multiple sclerosis (MS). Previous studies of DRB1
      variation and both MS susceptibility and phenotypic expression have lacked
      statistical power to detect modest genotypic influences, and have demonstrated
      conflicting results. Results derived from analyses of 1339 MS families indicate
      DRB1 variation influences MS susceptibility in a complex manner. DRB1*15 was
      strongly associated in families (P=7.8x10(-31)), and a dominant DRB1*15 dose
      effect was confirmed (OR=7.5, 95% CI=4.4-13.0, P<0.0001). A modest dose effect
      was also detected for DRB1*03; however, in contrast to DRB1*15, this risk was
      recessive (OR=1.8, 95% CI=1.1-2.9, P=0.03). Strong evidence for under
      transmission of DRB1*14 (P=5.7x10(-6)) even after accounting for DRB1*15 (P=0.03)
      was present, confirming a protective effect. In addition, a high risk DRB1*15
      genotype bearing DRB1*08 was identified (OR=7.7, 95% CI=4.1-14.4, P<0.0001),
      providing additional evidence for trans DRB1 allelic interactions in MS. Further,
      a significant DRB1*15 association observed in primary progressive MS families
      (P=0.0004), similar to relapsing-remitting MS families, suggests that DRB1
      related mechanisms are contributing to both phenotypes. In contrast, results
      obtained from 2201 MS cases argue convincingly that DRB1*15 genotypes do not
      modulate age of onset, or significantly influence disease severity measured using
      expanded disease disability score and disease duration. These results contribute
      substantially to our understanding of the DRB1 locus and MS, and underscore the
      importance of using large sample sizes to detect modest genetic effects,
      particularly in studies of genotype-phenotype relationships.

PMID- 16905562
TI  - Effect of a clinical pathway on the hospitalisation rates of children with
      asthma: a prospective study.
AB  - AIM: To determine the effect of implementing a clinical pathway, using evidence
      based clinical practice guidelines, for the emergency care of children and
      adolescents with asthma. METHODS: A prospective, before-after, controlled trial
      was conducted, which included patients aged 1-18 years who had acute
      exacerbations of asthma treated in a tertiary care paediatric emergency
      department. Data were collected for identical 2-month seasonal periods before and
      after implementation of the clinical pathway to determine hospitalisation rate
      and other outcomes. For 2 weeks after emergency visits, the rate at which
      patients returned to emergency care for worsening asthma was evaluated. A
      multidisciplinary panel, using national guidelines and a systematic review,
      developed the pathway. RESULTS: 267 patients were studied. The rate of
      hospitalisation was significantly lower in the post-implementation group (10/74;
      13.5%) than in the pre-implementation control group (53/193; 27.5%; p = 0.02;
      number needed to treat 7.1). All reduction in hospitalisation occurred in
      children with moderate to severe asthma exacerbation. After implementation of the
      clinical pathway, the rate of administration of oral corticosteroids to patients
      with moderate or severe exacerbations increased from 71% to 92% (p = 0.01), and
      significantly more patients received beta2-agonists in the first hour (p = 0.02).
      No significant change in relapse to acute care occurred within 2 weeks (p =
      0.19). CONCLUSIONS: An evidence-based clinical pathway for children and
      adolescents with moderate to severe exacerbations of acute asthma markedly
      decreases their rate of hospitalisation without increased return to emergency
      care.

PMID- 16905563
TI  - Postnatal factors associated with failure to thrive in term infants in the Avon
      Longitudinal Study of Parents and Children.
AB  - OBJECTIVE: To assess the contribution of postnatal factors to failure to thrive
      in infancy. METHODS: 11 900 infants from the Avon Longitudinal Study of Parents
      and Children (ALSPAC), born at 37-41 weeks' gestation, without major
      malformations and with a complete set of weight measurements in infancy (83% of
      the original ALSPAC birth cohort) were studied. Conditional weight gain was
      calculated for the periods from birth to 8 weeks and 8 weeks to 9 months. Cases
      of growth faltering were defined as those infants with a conditional weight gain
      below the 5th centile. RESULTS: Analysis yielded 528 cases of growth faltering
      from birth to 8 weeks and 495 cases from 8 weeks to 9 months. In multivariable
      analysis, maternal factors predicting poor infant growth were height <160 cm and
      age >32 years. Growth faltering between birth and 8 weeks was associated with
      infant sucking problems regardless of the type of milk, and with infant illness.
      After 8 weeks of age, the most important postnatal influences on growth were the
      efficiency of feeding, the ability to successfully take solids and the duration
      of breast feeding. CONCLUSIONS: The most important postnatal factors associated
      with growth faltering are the type and efficiency of feeding: no associations
      were found with social class or parental education. In the first 8 weeks of life,
      weak sucking is the most important symptom for both breastfed and bottle-fed
      babies. After 8 weeks, the duration of breast feeding, the quantity of milk taken
      and difficulties in weaning are the most important influences.

PMID- 16905564
TI  - Randomised controlled trial of the efficacy of a metered dose inhaler with bottle
      spacer for bronchodilator treatment in acute lower airway obstruction.
AB  - BACKGROUND: Inhaled bronchodilator treatment given via a metered dose inhaler
      (MDI) and spacer is optimal for relief of bronchoconstriction. Conventional
      spacers are expensive or unavailable in developing countries, but there is little
      information on the efficacy of low-cost spacers in young children. OBJECTIVE: To
      compare the response to bronchodilator treatment given via a conventional or a
      low-cost bottle spacer METHODS: A randomised controlled trial of the efficacy of
      a conventional spacer compared with a bottle spacer for bronchodilator treatment
      in young children with acute lower airway obstruction. Bronchodilator treatment
      was given from an MDI via an Aerochamber or a bottle spacer. Clinical score and
      oximetry recording were carried out before and after 15 min of treatment. MDI
      spacer treatment was repeated up to three times, depending on clinical response,
      after which nebulisation was used. The primary outcome was hospitalisation.
      RESULTS: 400 children, aged (median (25th-75th centile)) 12 (6-25) months, were
      enrolled. The number of children hospitalised (n = 60, 15%) was identical in the
      conventional and bottle spacer groups (n = 30, 15% in each). Secondary outcomes
      including change in clinical score (-2 (-3 to -1)), oxygen saturation (0 (-1 to
      1)) and number of bronchodilator treatments (2 (1 to 3)) were similar in both
      groups. Oral corticosteroids, prescribed for 78 (19.5%) children, were given to a
      similar number in the conventional (37 (18.5%)) and bottle spacer groups (41
      (20.5%)). CONCLUSION: A low-cost bottle spacer is as effective as a conventional
      spacer for bronchodilator treatment in young children with acute obstruction of
      the lower airways.

PMID- 16905565
TI  - A systematic review of lay views about infant size and growth.
AB  - OBJECTIVES: To understand lay views on infant size and growth and their
      implications for a British population. METHODS: A systematic review of parental
      and other lay views about the meanings and importance of infant size and growth
      using Medline, PsycInfo, CINAHL, Sociological Abstracts, IBSS, ASSIA, British
      Nursing Index ChildData, Caredata, SIGLE, Dissertation Abstracts (US), Index to
      Theses. 19 studies, most of which reported the views of mothers, from the US,
      Canada, the UK and Finland were reviewed. RESULTS: Notions of healthy size and
      growth were dominated by the concept of normality. Participants created norms by
      assessing and comparing size and growth against several reference points. When
      size or growth differed from these norms, explanations were sought for factors
      that would account for this difference. When no plausible explanation could be
      found, growth or size became a worry for parents. CONCLUSIONS: Parents consider
      the importance of contextual factors when judging what is appropriate or healthy
      growth. For public health advice to be effective, lay, as well as scientific,
      findings and values need to be considered.

PMID- 16905566
TI  - Blood pressure centiles for Great Britain.
AB  - OBJECTIVE: To produce representative cross-sectional blood pressure reference
      centiles for children and young people living in Great Britain. DESIGN: Analysis
      of blood pressure data from seven nationally representative surveys: Health
      Surveys for England 1995-8, Scottish Health Surveys 1995 and 1998, and National
      Diet & Nutrition Survey 1997. METHODS: Blood pressure was measured using the
      Dinamap 8100 with the same protocol throughout. Weight and height were also
      measured. Data for 11 364 males and 11,537 females aged 4-23 years were included
      in the analysis, after excluding 0.3% missing or outlying data. Centiles were
      derived for systolic, diastolic, mean arterial and pulse pressure using the
      lambda-mu-sigma [corrected] (LMS) equations method. RESULTS: Blood pressure in
      the two sexes was similar in childhood, rising progressively with age and more
      rapidly during puberty. Systolic pressure rose faster and was appreciably higher
      in adult men than in adult women. After adjustment for age, blood pressure was
      related more to weight than height, the effect being stronger for systolic blood
      pressure. Pulse pressure peaked at 18 years in males and 16 years in females.
      CONCLUSIONS: These centiles increase our knowledge of blood pressure norms in
      contemporary British children and young people. High blood pressure for age
      should be defined as blood pressure above the 98th centile, and high-normal blood
      pressure for age as blood pressure between the 91st and 98th centiles. The
      centiles identify children and young people with increased blood pressure, and
      will be of benefit to both clinical practice and research.

PMID- 16905568
TI  - Effect of light on seed germination of eight wetland Carex species.
AB  - BACKGROUND AND AIMS: In wetland plant communities, species-specific responses to
      pulses of white light and to red : far-red light ratios can vary widely and
      influence plant emergence from the seed bank. Carex species are the
      characteristic plants of sedge meadows of natural prairie wetlands in mid
      continental USA but are not returning to restored wetlands. Little is known about
      how light affects seed germination in these species-information which is
      necessary to predict seed bank emergence and to develop optimal revegetation
      practices. The effects of light on germination in eight Carex species from
      prairie wetlands were investigated. METHODS: Non-dormant seeds of eight Carex
      species were used to determine the influence of light on germination by
      examining: (a) the ability of Carex seeds to germinate in the dark; (b) the
      effect of different lengths of exposures to white light on germination; (c)
      whether the effect of white light can be replaced by red light; and (d) whether
      the germination response of Carex seeds to white or red light is photoreversible
      by far-red light. KEY RESULTS: Seeds of C. brevior and C. stipata germinated >25
      % in continuous darkness. Germination responses after exposure to different
      lengths of white light varied widely across the eight species. Carex brevior
      required <15 min of white light for > or =50 % germination, while C. hystericina,
      C. comosa, C. granularis and C. vulpinoidea required > or =8 h. The effect of
      white light was replaced by red light in all species. The induction of
      germination after exposure to white or red light was reversed by far-red light in
      all species, except C. stipata. CONCLUSIONS: The species-specific responses to
      simulated field light conditions suggest that (a) the light requirements for
      germination contribute to the formation of persistent seed banks in these species
      and (b) in revegetation efforts, timing seed sowing to plant community
      development and avoiding cover crops will improve Carex seed germination.

PMID- 16905567
TI  - Prevalence of acquired undescended testis in 6-year, 9-year and 13-year-old Dutch
      schoolboys.
AB  - OBJECTIVE: To investigate the prevalence of acquired undescended testis (UDT) in
      Dutch schoolboys. DESIGN AND PARTICIPANTS: As a part of routine school medical
      examinations, during a 2-year period (2001-3), testis position was determined in
      6-year, 9-year and 13-year-old schoolboys. Before the examination, a parent
      questionnaire was sent inquiring both about the position of the testes and
      whether the child had been admitted earlier to hospital for orchidopexy. In 6
      year and 13-year olds, a physical examination was performed by the school medical
      officer; in 9-year olds, a school nurse interview was held. Each boy for whom
      there was any doubt of the scrotal position was referred to the hospital for
      examination of both testes. SETTING: Institution for Youth Health Care
      "Noordkennemerland" and Medical Centre Alkmaar, Alkmaar, the Netherlands.
      RESULTS: Testis position was determined in 2042 boys aged 6, 1038 aged 9 and 353
      aged 13. Of these, 47, 53 and 8 boys, respectively, were referred to the hospital
      and seen for further evaluation. The diagnosis of acquired UDT was made in 25
      boys aged 6, 23 aged 9 and four aged 13. In 33 boys, a congenital UDT was
      diagnosed; 32 (97%) had already been diagnosed and treated at an early age.
      CONCLUSIONS: The prevalence of acquired UDT for 6-year, 9-year and 13-year olds
      was, respectively, 1.2% (25/2042), 2.2% (23/1038) and 1.1% (4/353). In addition,
      congenital UDT is treated during the early years of life and, in contrast with
      popular belief, screening programmes for detecting UDT in the early years are
      successful.

PMID- 16905569
TI  - When, how and how much: Gender-specific resource-use strategies in the dioecious
      tree Juniperus thurifera.
AB  - BACKGROUND AND AIMS: In dioecious species male and female plants experience
      different selective pressures and often incur different reproductive costs. An
      increase in reproductive investment habitually results in a reduction of the
      resources available to other demands, such as vegetative growth. Tree-ring growth
      is an integrative measure that tracks vegetative investment through the plant's
      entire life span. This allows the study of gender-specific vegetative allocation
      strategies in dioecious tree species thoughout their life stages. METHODS:
      Standard dendrochronological procedures were used to measure tree-ring width.
      Analyses of time-series were made by means of General Mixed Models with
      correction of autocorrelated values by the use of an autoregressive covariance
      structure of order one. Bootstrapped correlation functions were used to study the
      relationship between climate and tree-ring width. KEY RESULTS: Male and female
      trees invest a similar amount of resources to ring growth during the early life
      stages of Juniperus thurifera. However, after reaching sexual maturity, tree-ring
      growth is reduced for both sexes. Furthermore, females experience a significantly
      stronger reduction in growth than males, which indicates a lower vegetative
      allocation in females. In addition, growth was positively correlated with
      precipitation from the current winter and spring in male trees but only to
      current spring precipitation in females. CONCLUSIONS: Once sexual maturity is
      achieved, tree rings grow proportionally more in males than in females.
      Differences in tree-ring growth between the genders could be a strategy to
      respond to different reproductive demands. Therefore, and responding to the
      questions of when, how and how much asked in the title, it is shown that male
      trees invest more resources to growth than female trees only after reaching
      sexual maturity, and they use these resources in a different temporal way.

PMID- 16905570
TI  - Cognitive outcome and cyclo-oxygenase-2 gene (-765 G/C) variation in the preterm
      infant.
AB  - BACKGROUND: Cyclo-oxygenase (COX) inhibition by indomethacin does not result in
      an improvement in long-term neurocognitive outcome, despite reducing the
      incidence of both severe intraventricular haemorrhage and white matter injury
      visible on ultrasound. Diffuse brain injury after preterm birth may have
      inflammatory origins. These two points suggest that, in the preterm brain, COX
      inhibition may have a dominant proinflammatory or neuropathological role. The
      inducible form of the COX2 gene is polymorphic: the -765 C (rather than G)
      variant of the gene is associated with reduced COX2 activity. OBJECTIVE: To test
      the hypothesis that the C allele of COX2 is associated with worse
      neurodevelopmental outcomes after premature birth. OUTCOMES: Cerebral palsy,
      disability, Griffith's developmental quotient at 2 years and British Ability
      Scales-11 general cognitive ability and motor performance (movement assessment
      battery for children) at 5(1/2) years were compared with COX2 genotype. RESULTS:
      The C allele (GC 65 (31%), CC 3 (1%)) was independently associated with worse
      cognitive performance at 2 and 5(1/2) years: C allele mean (SEM) developmental
      quotient 92.7 (1.7), v GG 97.6 (1.5), p = 0.039; C allele mean (SEM) general
      cognitive ability, 94.3 (2.2) v GG 100.9 (1.7), p = 0.028. CONCLUSION: An
      antineuropathological role for COX2 in the preterm brain may help account for the
      lack of effect of indomethacin treatment in improving neurocognitive outcomes in
      children born preterm, despite reported reduction in apparent brain injury.

PMID- 16905571
TI  - Frontal cerebral blood flow change associated with infant-directed speech.
AB  - OBJECTIVE: To examine the auditory perception of maternal utterances by neonates
      using near-infrared spectroscopy (NIRS). METHODS: Twenty full-term, healthy
      neonates were included in this study. The neonates were tested in their cribs
      while they slept in a silent room. First, two probe holders were placed on the
      left and right sides of the forehead over the eyebrows using double-sided
      adhesive tape. The neonates were then exposed to auditory stimuli in the form of
      infant-directed speech (IDS) or adult-directed speech (ADS), sampled from each of
      the mothers, through an external auditory speaker. RESULTS: A 2 (stimulus: IDS
      and ADS) x 2 (recording site: channel 1 (right side) and channel 2 (left side))
      analysis of variance for these relative oxygenated haemoglobin values showed that
      IDS (Mean = 0.25) increased brain function significantly (F = 3.51) more than ADS
      (Mean = -0.26). CONCLUSIONS: IDS significantly increased brain function compared
      with ADS. These results suggest that the emotional tone of maternal utterances
      could have a role in activating the brains of neonates to attend to the
      utterances, even while sleeping.

PMID- 16905572
TI  - Effect of oestradiol and progesterone replacement on bronchopulmonary dysplasia
      in extremely preterm infants.
AB  - OBJECTIVE: To study whether postnatal replacement of oestradiol and progesterone
      may help to prevent bronchopulmonary dysplasia (BPD). METHODS: This randomised
      placebo-controlled double-blind study enrolled 83 infants of <29 weeks
      gestational age and 1000 g birth weight requiring mechanical ventilation within
      12 h after birth. Oestradiol (2.5 mg/kg/day) and progesterone (22.5 mg/kg/day)
      were given by continuous intravenous infusion of a standard lipid emulsion (15
      ml/kg/day) in the replacement group (ESTRA-PRO). The placebo group received the
      same lipid emulsion without oestradiol or progesterone. A replacement period of
      at least 2 weeks but not >4 weeks was strived for and defined as "according to
      protocol". The primary outcome variable was the incidence of BPD or death.
      RESULTS: The median birth weight was 670 g (min-max 400-990 g) and the
      gestational age 25 weeks (23.1-28.1 weeks). The incidence of BPD or death was 48%
      in the placebo group and 44% in the ESTRA-PRO group (p = 0.38, one-sided testing,
      intention to treat analysis). In infants treated according to protocol, 32% (9 of
      28) in the placebo group and 14% (3 of 21) in the ESTRA-PRO group developed BPD
      (p = 0.08). CONCLUSION: Replacement of oestradiol and progesterone was not
      effective for prevention of BPD or death in extremely preterm born infants.
      Better-powered trials are needed to evaluate this new approach.

PMID- 16905573
TI  - Respiratory outcome in late childhood after neonatal continuous negative pressure
      ventilation.
AB  - BACKGROUND: The outcome in late childhood for children entered into a randomised
      trial of continuous negative extrathoracic pressure (CNEP) versus standard
      respiratory management for the treatment of neonatal respiratory distress was
      studied. In the original trial, there were advantages in the duration of oxygen
      and the prevalence of chronic lung disease for those assigned to receive CNEP.
      AIM: To determine whether the above differences had persisted into childhood.
      METHODS: Outpatient evaluation of children by a paediatrician using Spirometry
      (Vitalograph Spirometer 2120, Ennis, Ireland) and MicroRint (Micro Medical,
      Rochester, Kent, UK) techniques independently of the original trial. Parents
      completed questionnaires about their child's respiratory history and social
      demographic information. RESULTS: 133 (65%) survivors were evaluated at 9.6-14.9
      years of age. The group examined were representative of the original cohort and
      no significant baseline differences were observed between children evaluated who
      had been allocated to CNEP or standard treatments. We compared Rint (before and
      after bronchodilator) and forced expiratory flow, volume and vital capacity
      between the two study groups; none were significant. Children in the standard
      group had received paediatric intensive care more often (p = 0.19) and were more
      likely to be receiving inhaled drugs for asthma (p = 0.19; all not significant).
      CONCLUSIONS: No important differences were found at follow-up in late childhood
      in respiratory outcomes for children treated with neonatal CNEP or standard
      treatment. Caution should be exercised, as the original trial was not powered to
      show these differences, but there seems to be no long-term detriment in
      respiratory outcomes for children treated with CNEP in the neonatal period.

PMID- 16905574
TI  - Transporting newborn infants with suspected duct dependent congenital heart
      disease on low-dose prostaglandin E1 without routine mechanical ventilation.
AB  - AIM: To evaluate the safety of transporting newborn infants with suspected duct
      dependent congenital heart disease (CHD) treated with prostaglandin E1 (PGE1)
      without routine mechanical ventilation. METHODS: A retrospective population-based
      audit of newborn infants with suspected CHD transported on PGE1 by the New South
      Wales newborn and paediatric Transport Service from 1995 through 2005. RESULTS:
      Mechanical ventilation was not used prior to treatment with PGE1 in 94 (31%) of
      the 300 infants. The indications for mechanical ventilation in the remaining 206
      infants (69%) included elective mechanical ventilation because of the intention
      to use PGE1 (n = 125) and severe hypoxaemia, acidosis or cardiorespiratory
      failure prior to commencing PGE1 (n = 81). 16 (17%) of the 94 infants who were
      not ventilated initially required mechanical ventilation before transport because
      of apnoea, which developed within one hour of commencing PGE1. 2 (2.6%) of the 78
      infants transported without mechanical ventilation developed apnoea in transit
      and both were receiving >or=15 ng/kg/min of PGE1. Apnoea was more likely to occur
      in non-ventilated infants when the PGE1 infusion rate was >or=15 ng/kg/min
      compared with <15 ng/kg/min (14/33 vs 4/61, chi(2) = 15.55, p<.001). CONCLUSIONS:
      Newborn infants with suspected duct dependent CHD treated with low dose PGE1 (<15
      ng/kg/min) may not require mechanical ventilation for safe transport.

PMID- 16905576
TI  - Cell-ELISA detection of antineuronal antibodies in central nervous system
      involvement in systemic lupus erythematosus.
AB  - OBJECTIVE: To develop a cell-ELISA method to detect antineuronal antibodies (anti
      Ns) and evaluate the diagnostic value of anti-Ns in central nervous system
      involvement in systemic lupus erythematosus (CNS-SLE). METHOD: Anti-N was
      assessed in both serum and cerebrospinal fluid (CSF) samples from 38 patients
      with CNS-SLE, 29 with SLE without CNS involvement (non-CNS-SLE), 36 with other
      rheumatic diseases and 59 with non-rheumatic diseases with the CNS manifestations
      using a cell-ELISA method with 1% paraformaldehyde-fixed SK-N-MC neuroblastoma
      cells as substrate. Serum samples from 37 healthy donors were also included in
      this study. Patients with CNS-SLE who were anti-N positive in CSF were studied
      serially for CSF anti-N levels at times of treatment-associated improvement in
      CNS symptoms. RESULTS: Serum anti-N levels were significantly increased in
      patients with SLE compared with other groups, with a sensitivity of 61.2% (41/67)
      and a specificity of 91.8% (p<0.001). CSF anti-N levels were significantly
      increased in patients with CNS-SLE, with a sensitivity of 47.4% (18/38) and a
      specificity of 89.7%, whereas only 10.3% (3/29) of patients with non-CNS-SLE had
      increased anti-N in CSF (p<0.001). CSF anti-N levels decreased significantly
      after effective treatment of CNS-SLE (p<0.05). CONCLUSION: Serum anti-N is
      relatively specific to SLE. CSF anti-N is a sensitive and relatively specific
      antibody in diagnosing CNS-SLE and correlates with CNS-SLE activity.

PMID- 16905575
TI  - Biochemical and functional characterization of three activated macrophage
      populations.
AB  - We generated three populations of macrophages (Mphi) in vitro and characterized
      each. Classically activated Mphi (Ca-Mphi) were primed with IFN-gamma and
      stimulated with LPS. Type II-activated Mphi (Mphi-II) were similarly primed but
      stimulated with LPS plus immune complexes. Alternatively activated Mphi (AA-Mphi)
      were primed overnight with IL-4. Here, we present a side-by-side comparison of
      the three cell types. We focus primarily on differences between Mphi-II and AA
      Mphi, as both have been classified as M2 Mphi, distinct from Ca-Mphi. We show
      that Mphi-II more closely resemble Ca-Mphi than they are to AA-Mphi. Mphi-II and
      Ca-Mphi, but not AA-Mphi, produce high levels of NO and have low arginase
      activity. AA-Mphi express FIZZ1, whereas neither Mphi-II nor Ca-Mphi do. Mphi-II
      and Ca-Mphi express relatively high levels of CD86, whereas AA-Mphi are virtually
      devoid of this costimulatory molecule. Ca-Mphi and Mphi-II are efficient APC,
      whereas AA-Mphi fail to stimulate efficient T cell proliferation. The differences
      between Ca-Mphi and Mphi-II are more subtle. Ca-Mphi produce IL-12 and give rise
      to Th1 cells, whereas Mphi-II produce high levels of IL-10 and thus, give rise to
      Th2 cells secreting IL-4 and IL-10. Mphi-II express two markers that may be used
      to identify them in tissue. These are sphingosine kinase-1 and LIGHT (TNF
      superfamily 14). Thus, Ca-Mphi, Mphi-II, and AA-Mphi represent three populations
      of cells with different biological functions.

PMID- 16905577
TI  - Differential effect of methotrexate on the increased CCR2 density on circulating
      CD4 T lymphocytes and monocytes in active chronic rheumatoid arthritis, with a
      down regulation only on monocytes in responders.
AB  - OBJECTIVES: To evaluate the effect of orally administered methotrexate (MTX) on
      the density of CC chemokine receptor 2 (CCR2) and CXC chemokine receptor 3
      (CXCR3) on circulating monocytes, and the coexpression of CXCR3 and CCR2 on CD4 T
      lymphocytes in patients with active chronic rheumatoid arthritis. METHODS: All 34
      patients with rheumatoid arthritis fulfilled the 1987 American Rheumatism
      Association criteria and were followed for 16 weeks after starting MTX.
      Peripheral blood mononuclear cells were analysed for CCR2 and CXCR3 density by
      three-colour flow cytometry before initiation of MTX and at week 12. RESULTS: 22
      (65%) patients were non-responders, 12 (35%) patients responded to MTX by
      American College of Rheumatology (ACR)20% criteria, and 8 (24%) of these patients
      responded by ACR50%. In patients with active rheumatoid arthritis before starting
      MTX, CCR2 density on circulating monocytes, CD4(+) CXCR3(+) and CD4(+) CXCR3(-) T
      lymphocytes was increased compared with controls. During 12 weeks of MTX
      treatment, the CCR2 density on monocytes decreased significantly in the ACR50%
      group but not in the ACR20% and non-responder groups. The increased CCR2 density
      on CD4(+) CXCR3(+) and CD4(+) CXCR3(-) T lymphocytes was unaffected by the
      reduction in disease activity measured in relation to MTX treatment. The
      percentage of both monocytes and CD4(+) CXCR3(+) and CD4+ CXCR3(-) T lymphocytes
      among the peripheral circulating mononuclear cells did not change during MTX
      treatment. CONCLUSIONS: Active chronic rheumatoid arthritis is characterised by
      enhanced CCR2 density on circulating monocytes and CD4(+) CXCR3(+) and CD4(+)
      CXCR3(-) T lymphocytes. During MTX treatment, a decrease in CCR2 density on
      monocytes in the ACR50% responder group was associated with decreased disease
      activity. The increased CCR2 density on CD4(+) CXCR3(+) and CD4(+) CXCR3(-) T
      lymphocytes was uninfluenced by MTX and disease activity.

PMID- 16905578
TI  - Methotrexate pharmacogenomics.

PMID- 16905580
TI  - Sulphate and osteoarthritis: decrease of serum sulphate levels by an additional 3
      h fast and a 3-h glucose tolerance test after an overnight fast.
AB  - BACKGROUND: Low sulphate levels in blood may contribute to osteoarthritis by
      decreasing cartilage chondroitin sulphation. OBJECTIVE: To measure serum levels
      of sulphate during 3 h of fasting or glucose ingestion after overnight fasts to
      determine how much sulphate lowering may occur during this period. METHODS: Sera
      from 14 patients with osteoarthritis who fasted overnight were obtained every 15
      30 min during 3 h of continued fasting and during 3 h after ingestion of 75 g of
      glucose. Sulphate was assayed by high-performance liquid chromatography with a
      Metrohm-Peak 761 Compact IC and simultaneously assayed for glucose by high
      performance liquid chromatography with a Metrohm-Peak 817 Bioscan. RESULTS:
      Continuation of overnight fasting for 3 h resulted in a near-linear 3-h decrease
      in levels for all 14 patients ranging from 3% to 20% with a mean drop of 9.3%,
      whereas the 3-h decrease after glucose ingestion ranged from 10% to 33% with a
      mean drop of 18.9%. CONCLUSION: A 3-h continuation of fasting caused a marked
      reduction in serum sulphate levels, whereas ingestion of 75 g of glucose in the
      absence of protein resulted in doubling the reduction. This suggests that fasting
      and ingestion of protein-free calories may produce periods of chondroitin
      undersulphation that could affect osteoarthritis.

PMID- 16905581
TI  - Hyperparathyroid bone disease--an unusual and memorable condition.

PMID- 16905579
TI  - Systemic lupus erythematosus in a multiethnic cohort: LUMINA XXXV. Predictive
      factors of high disease activity over time.
AB  - AIM: To ascertain the predictive factors of high levels of disease activity in
      systemic lupus erythematosus (SLE). PATIENTS AND METHODS: Patients with SLE
      (American College of Radiology criteria), aged >or=16 years, with disease
      duration <or=5 years and of Hispanic (Texas and Puerto Rico), African American
      and Caucasian ethnicities, were included. The outcome was high disease activity
      at any time (Systemic Lupus Activity Measure-Revised >10). A basic multivariable
      model (including age, sex, ethnicity, health insurance, social support, abnormal
      illness-related behaviours, helplessness and prior disease activity) was first
      examined. Additional models were built by including other variables. RESULTS: 554
      patients (100 Hispanics from Texas, 94 Hispanics from Puerto Rico, 199 African
      Americans, 161 Caucasians) and 2366 visits were analysed; 47% of the patients and
      29% of the visits met the definition of high disease activity (more common among
      African Americans (72.0%) and Hispanics from Texas (71.3%) than among Caucasians
      (43.9%) and Hispanics from Puerto Rico (31.9%)). Variables found to predict high
      levels of disease activity were Hispanic (from Texas) and African American
      ethnicities, lack of health insurance, helplessness, abnormal illness-related
      behaviours and poor social support; age was negatively associated with high
      levels of disease activity. African admixture and anti-double-stranded DNA
      antibodies also predicted high levels of disease activity, as did prior disease
      activity. None of the human leucocyte antigen variables were retained in the
      models. CONCLUSIONS: Socioeconomic-demographic (age, ethnicity, health
      insurance), behavioural and psychological variables are important mediators of
      high levels of disease activity in SLE during its course. Interventions aimed at
      modifiable factors may improve the outcomes of SLE.

PMID- 16905582
TI  - Targeting activated T cells: successful use of anti-CD25 monoclonal antibody
      basiliximab in a patient with systemic sclerosis.

PMID- 16905583
TI  - Resolution of sclerodermatous myocarditis after autologous stem cell
      transplantation.

PMID- 16905584
TI  - Dyslipidaemia in Behcet's disease as a thrombotic risk factor.

PMID- 16905585
TI  - High levels of human anti-human antibodies to adalimumab in a patient not
      responding to adalimumab treatment.

PMID- 16905586
TI  - Easy assessment of axial spondyloarthritis (early ankylosing spondylitis) at the
      bedside.

PMID- 16905587
TI  - Examining the exhaled levels of hydrogen peroxide in rheumatoid arthritis: a
      pilot study.

PMID- 16905588
TI  - The presence of forefoot problems and the role of surgery in patients with
      rheumatoid arthritis.

PMID- 16905589
TI  - Soluble fractalkine in the cerebrospinal fluid of patients with neuropsychiatric
      lupus.

PMID- 16905590
TI  - Psoriasis after treatment of juvenile idiopathic arthritis with etanercept.

PMID- 16905591
TI  - Incorporating monotonicity into the evaluation of a biomarker.
AB  - In the assessment of clinical utility of biomarkers, case-control studies are
      often undertaken based on existing serum samples. A common assumption made in
      these studies is that higher levels of the biomarker are associated with
      increased disease risk. In this article, we consider methods of analysis in which
      monotonicity is incorporated in associating the biomarker and the clinical
      outcome. We consider the roles of discrimination versus association and assess
      methods for both goals. In addition, we propose a semiparametric isotonic
      regression model for binary data and describe a simple estimation procedure as
      well as attendant inferential procedures. We apply the various methodologies to
      data from a prostate cancer study involving a serum biomarker.

PMID- 16905592
TI  - Altered neocortical cell density and layer thickness in serotonin transporter
      knockout mice: a quantitation study.
AB  - The neurotransmitter serotonin (5-HT) plays morphogenetic roles during
      development, and their alteration could contribute to autism pathogenesis in
      humans. To further characterize 5-HT's contributions to neocortical development,
      we assessed the thickness and neuronal cell density of various cerebral cortical
      areas in serotonin transporter (5-HTT) knockout (ko) mice, characterized by
      elevated extracellular 5-HT levels. The thickness of layer IV is decreased in 5
      HTT ko mice compared with wild-type (wt) mice. The overall effect on cortical
      thickness, however, depends on the genetic background of the mice. Overall
      cortical thickness is decreased in many cortical areas of 5-HTT ko mice with a
      mixed c129-CD1-C57BL/6J background. Instead, 5-HTT ko mice backcrossed into the
      C57BL/6J background display increases in supragranular and infragranular layers,
      which compensate entirely for decreased layer IV thickness, resulting in
      unchanged or even enhanced cortical thickness. Moreover, significant increases in
      neuronal cell density are found in 5-HTT ko mice with a C57BL/6J background
      (wt:hz:ko ratio = 1.00:1.04:1.17) but not in the mixed c129-CD1-C57BL/6J 5-HTT ko
      animals. These results provide evidence of 5-HTT gene effects on neocortical
      morphology in epistatic interaction with genetic variants at other loci and may
      model the effect of functional 5-HTT gene variants on neocortical development in
      autism.

PMID- 16905593
TI  - Duration-dependent FMRI adaptation and distributed viewer-centered face
      representation in human visual cortex.
AB  - Two functional magnetic resonance imaging (fMRI) face viewpoint adaptation
      experiments were conducted to investigate whether fMRI adaptation in high-level
      visual cortex depends on the duration of adaptation and how different views of a
      face are represented in the human visual system. We found adaptation effects in
      multiple face-selective areas, which suggest a distributed, viewer-centered
      representation of faces in the human visual system. However, the nature of the
      adaptation effects was dependent on the length of adaptation. With long
      adaptation durations, face-selective areas along the hierarchy of the visual
      system gradually exhibited viewpoint-tuned adaptation. As the angular difference
      between the adapter and test stimulus increased, the blood oxygen level-dependent
      (BOLD) signal evoked by the test stimulus gradually increased as a function of
      the amount of 3-dimensional (3D) rotation. With short adaptation durations,
      however, face-selective areas in the ventral pathway, including the lateral
      occipital cortex and right fusiform area, exhibited viewpoint-sensitive
      adaptation. These areas showed an increase in the BOLD signal with a 3D rotation,
      but this signal increase was independent of the amount of rotation. Further, the
      right superior temporal sulcus showed little or very weak viewpoint adaptation
      with short adaptation durations. Our findings suggest that long- and short-term
      fMRI adaptations may reflect selective properties of different neuronal
      mechanisms.

PMID- 16905594
TI  - A 1-D model to explore the effects of tissue loading and tissue concentration
      gradients in the revised Starling principle.
AB  - The recent experiments in Hu et al. (Am J Physiol Heart Circ Physiol 279: H1724
      H1736, 2000) and Adamson et al. (J Physiol 557: 889-907, 2004) in frog and rat
      mesentery microvessels have provided strong evidence supporting the Michel
      Weinbaum hypothesis for a revised asymmetric Starling principle in which the
      Starling force balance is applied locally across the endothelial glycocalyx layer
      rather than between lumen and tissue. These experiments were interpreted by a
      three-dimensional (3-D) mathematical model (Hu et al.; Microvasc Res 58: 281-304,
      1999) to describe the coupled water and albumin fluxes in the glycocalyx layer,
      the cleft with its tight junction strand, and the surrounding tissue. This
      numerical 3-D model converges if the tissue is at uniform concentration or has
      significant tissue gradients due to tissue loading. However, for most
      physiological conditions, tissue gradients are two to three orders of magnitude
      smaller than the albumin gradients in the cleft, and the numerical model does not
      converge. A simpler multilayer one-dimensional (1-D) analytical model has been
      developed to describe these conditions. This model is used to extend Michel and
      Phillips's original 1-D analysis of the matrix layer (J Physiol 388: 421-435,
      1987) to include a cleft with a tight junction strand, to explain the observation
      of Levick (Exp Physiol 76: 825-857, 1991) that most tissues have an equilibrium
      tissue concentration that is close to 0.4 lumen concentration, and to explore the
      role of vesicular transport in achieving this equilibrium. The model predicts the
      surprising finding that one can have steady-state reabsorption at low pressures,
      in contrast to the experiments in Michel and Phillips, if a backward-standing
      gradient is established in the cleft that prevents the concentration from rising
      behind the glycocalyx.

PMID- 16905595
TI  - Severity of myocardial injury following ischemia-reperfusion is increased in a
      mouse model of allergic asthma.
AB  - Cardiovascular disease is common in asthmatic patients but often is attributed to
      respiratory drug therapy. With mounting evidence for an inflammatory role in the
      development of cardiovascular disease, we hypothesized that the inflammation
      associated with asthma adversely affects the cardiovascular system independent of
      therapeutic interventions. The hypothesis was tested in a murine model of
      myocardial ischemia-reperfusion injury. BALB/C mice were sensitized by
      intraperitoneal injection of ragweed (RW) or normal saline (NS) and challenged by
      intratracheal instillation of RW or NS. Effective allergic sensitization and
      challenge were confirmed by hyperresponsiveness to aerosolized methacholine and
      bronchoalveolar lavage. In vivo myocardial ischemia-reperfusion injury was
      induced by ligation of the left anterior descending artery for 20 min, followed
      by reperfusion for 2 h. The infarct size (% risk area) and neutrophil density in
      the myocardial area at risk were significantly higher in the RW/RW group than in
      the control groups. The tissue neutrophil count correlated with the infarct size
      but did not correlate with blood neutrophil counts. Furthermore, in the RW/RW
      group, circulating granulocytes showed an enhanced expression of CD11b and P
      selectin glycoprotein ligand-1, enhanced stimulated release of myeloperoxidase,
      and enhanced expression of P-selectin in the coronary vasculature. These results
      indicate that allergic responses in the airways enhance expression of attachment
      molecules in coronary vasculature and activate circulating neutrophils, resulting
      in recruitment of highly activated neutrophils to the infarct zone during an
      acute ischemia-reperfusion event, thereby enhancing tissue destruction.

PMID- 16905596
TI  - Resistin impairs endothelium-dependent dilation to bradykinin, but not
      acetylcholine, in the coronary circulation.
AB  - Elevated plasma levels of fat-derived signaling molecules are associated with
      obesity, vascular endothelial dysfunction, and coronary heart disease; however,
      little is known about their direct coronary vascular effects. Accordingly, we
      examined mechanisms by which one adipokine, resistin, affects coronary vascular
      tone and endothelial function. Studies were conducted in anesthetized dogs and
      isolated coronary artery rings. Resistin did not change coronary blood flow, mean
      arterial pressure, or heart rate. Resistin had no effect on acetylcholine-induced
      relaxation of artery rings; however, resistin did impair bradykinin-induced
      relaxation. Selective impairment was also observed in vivo, as resistin
      attenuated vasodilation to bradykinin but not to acetylcholine. Resistin had no
      effect on dihydroethidium fluorescence, an indicator of superoxide (O(2)(-))
      production, and the inhibitory effect of resistin on bradykinin-induced
      relaxation persisted in the presence of Tempol, a superoxide dismutase mimetic.
      To determine whether resistin impaired production of and/or responses to nitric
      oxide (NO) or prostaglandins (e.g., prostacyclin; PGI(2)), we performed
      experiments with N(omega)-nitro-L-arginine methyl ester (L-NAME) and
      indomethacin. The effect of resistin to attenuate bradykinin-induced vasodilation
      persisted in the presence of L-NAME or indomethacin, suggesting resistin may act
      at a cell signaling point upstream of NO or PGI(2) production. Resistin-induced
      endothelial dysfunction is not generalized, and it is not consistent with effects
      mediated by O(2)(-) or interference with NO or PGI(2) signaling. The site of the
      resistin-induced impairment is unknown but may be at the bradykinin receptor or a
      closely associated signal transduction machinery proximal to NO synthase or
      cyclooxygenase.

PMID- 16905597
TI  - Left ventricular pressure-volume relationship in conscious mice.
AB  - With the availability of transgenic models, the mouse has become an increasingly
      important subject for genetic-hemodynamic studies. Recently, we developed a
      technique to measure left ventricular (LV) pressure in conscious mice with an
      implanted LV polyethylene tube. We extended our new method by evaluating the LV
      pressure-volume relationship and examined the feasibility of this method in this
      study. We studied 17 male mice (age, 11-20 wk) with a conductance catheter
      inserted into the LV through the polyethylene tube. Load-independent parameters
      of contractility derived from pressure-volume relationship [slope of the end
      systolic pressure-volume relationship (E(es)), slope of the maximum first
      derivative of LV pressure (dP/dt(max))-end-diastolic volume (EDV) relation, and
      preload-recruitable stroke work (PRSW)] were evaluated by inferior vena caval
      occlusion with an implanted snare. LV function assessed by this technique on two
      different days showed that the parameters were very similar, indicating
      reproducibility. Both linear and nonlinear regression analyses were performed for
      E(es). Contractility was enhanced by isoproterenol (E(es), 13.1 +/- 6.6 to 20.8
      +/- 8.7 mmHg/microl; dP/dt(max)-EDV, 496 +/- 139 to 825 +/- 178 mmHg.s(
      1).microl(-1); and PRSW, 110 +/- 23 to 127 +/- 21 mmHg), depressed by atenolol
      (E(es), 14.5 +/- 6.1 to 4.6 +/- 2.0 mmHg/microl; dP/dt(max)-EDV, 543 +/- 188 to
      185 +/- 94 mmHg.s(-1).microl(-1); and PRSW, 117 +/- 20 to 70 +/- 15 mmHg) and
      isoflurane (E(es), 12.3 +/- 6.0 to 5.7 +/- 2.1 mmHg/microl; dP/dt(max)-EDV, 528
      +/- 172 to 164 +/- 68 mmHg/s.microl; and PRSW, 124 +/- 19 to 48 +/- 10 mmHg),
      significantly. In conclusion, this is the first description of the LV pressure
      volume relationship in conscious mice. These findings suggest that this method is
      feasible to detect changes of contractility in the conscious state, allowing
      serial assessment of pressure-volume-derived cardiac function indexes over time
      without anesthesia or repeated surgery.

PMID- 16905598
TI  - Long-term mineralocorticoid receptor blockade reduces fibrosis and improves
      cardiac performance and coronary hemodynamics in elderly SHR.
AB  - Aldosterone has been implicated as one of the mediators of cardiovascular injury
      in various diseases. This study examines whether mineralocorticoid antagonism
      ameliorates or prevents the adverse cardiac effects of hypertension and aging.
      Male 22-wk-old spontaneously hypertensive rats (SHR) were divided into two
      groups, 15 rats in each. One group received no treatment; the other was given
      eplerenone ( approximately 100 mg.kg(-1).day(-1)). At the age of 54 wk, indexes
      of cardiovascular mass, systemic and regional hemodynamics, including coronary,
      left ventricular function, and myocardial collagen content, were determined in
      all rats. Hemodynamic studies were done in conscious rats. Arterial pressure was
      lowered only slightly in eplerenone-treated rats, and cardiac output and total
      peripheral resistance did not differ from control rats. Left and right
      ventricular and aortic mass indexes were unaffected by eplerenone; however,
      concentration of hydroxyproline in the right and left ventricle was decreased
      significantly (P < 0.05) by eplerenone. This was accompanied by an improvement in
      left ventricular diastolic function and coronary hemodynamics. In conclusion,
      long-term therapy with the mineralocorticoid receptor antagonist eplerenone
      ameliorated adverse cardiac effects of both hypertension and aging in SHR. Thus
      reduction in myocardial fibrosis, paralleled by improvements in left ventricular
      function and coronary hemodynamics, was observed in eplerenone-treated SHR.

PMID- 16905599
TI  - Acute ascorbate supplementation alone or combined with arginase inhibition
      augments reflex cutaneous vasodilation in aged human skin.
AB  - Full expression of reflex cutaneous vasodilation (VD) is dependent on nitric
      oxide (NO) and is attenuated in older humans. NO may be decreased by an age
      related increase in reactive oxygen species or a decrease in L-arginine
      availability via upregulated arginase. The purpose of this study was to determine
      the effect of acute antioxidant supplementation alone and combined with arginase
      inhibition on reflex VD in aged skin. Eleven young (Y; 22 +/- 1 yr) and 10 older
      (O; 68 +/- 1 yr) human subjects were instrumented with four intradermal
      microdialysis (MD) fibers. MD sites were control (Co), NO synthase inhibited (NOS
      I), L-ascorbate supplemented (Asc), and Asc + arginase-inhibited (Asc + A-I).
      After baseline measurements, subjects underwent whole body heating to increase
      oral temperature (T(or)) by 0.8 degrees C. Red blood cell flux was measured by
      using laser-Doppler flowmetry, and cutaneous vascular conductance (CVC) was
      calculated (CVC = flux/mean arterial pressure) and normalized to maximal
      (CVC(max)). VD during heating was attenuated in O (Y: 37 +/- 3 vs. O: 28 +/- 3%
      CVC(max); P < 0.05). NOS-I decreased VD in both groups compared with Co (Y: 20 +/
      4; O: 15 +/- 2% CVC(max); P < 0.05 vs. Co within group). Asc and Asc + A-I
      increased VD beyond Co in O (Asc: 35 +/- 4% CVC(max); Asc + A-I: 41 +/- 3%
      CVC(max); P < 0.001) but not in Y (Asc: 36 +/- 3% CVC(max); Asc + A-I: 40 +/- 5%
      CVC(max); P > 0.05). Combined Asc + A-I resulted in a greater increase in VD than
      Asc alone in O (P = 0.001). Acute Asc supplementation increased reflex VD in aged
      skin. Asc combined with arginase inhibition resulted in a further increase in VD
      above Asc alone, effectively restoring CVC to the level of young subjects.

PMID- 16905600
TI  - Chronic hyperglycemia impairs functional vasodilation via increasing thromboxane
      receptor-mediated vasoconstriction.
AB  - Individuals with hyperglycemia exhibit impaired exercise performance and
      functional vasodilatory response. Based on the importance of arachidonic acid
      (AA) metabolites in functional vasodilation and the increased thromboxane-to
      prostacyclin ratio in diabetes, we hypothesized that chronic hyperglycemia in
      diabetes increases thromboxane-receptor (TP)-mediated vasoconstriction, resulting
      in an attenuated functional vasodilation. Three groups of lean Zucker rats (8 wk)
      were used to test the effects of chronic hyperglycemia on endothelial function:
      normal, streptozotocin (STZ; 70 mg/kg ip), and STZ + insulin (2 U/day). After 4
      wk of treatment, spinotrapezius arcade arterioles were chosen for
      microcirculatory observation. Arteriolar diameter was measured following muscle
      stimulation and 10 microM AA application in the absence and presence of 1 microM
      SQ-29548 (TP antagonist). STZ rats exhibited significantly higher fasting glucose
      levels and attenuated functional and AA-induced dilation compared with normal
      animals. SQ-29548 improved the vasodilatory responses in STZ rats but had no
      effect in controls. Insulin treatment normalized both the glucose levels and the
      vasodilatory responses, and SQ-29548 treatment had no effect on functional or AA
      mediated vasodilation in STZ + insulin animals. These results suggest that the
      impaired functional vasodilation in diabetic rats is due to hyperglycemia
      mediated increases in TP-mediated vasoconstriction.

PMID- 16905601
TI  - Effects of intravascular infusions of plasma on placental and systemic blood flow
      in fetal sheep.
AB  - Six singleton fetal sheep of 118-122 days gestational age were instrumented with
      flow sensors on the brachiocephalic artery, the postductal aorta, and the common
      umbilical artery and with arterial and venous intravascular catheters. At 125-131
      days of gestation, we started week-long continuous recordings of flows and
      pressures. After control measures had been obtained, the fetuses were given
      continuous intravenous infusions of adult sheep plasma at an initial rate of 229
      ml/day. After 1 wk of infusion, fetal plasma protein concentrations had increased
      from 34 to 78 g/l, arterial and venous pressures had increased from 42 to 64 and
      from 2.7 to 3.7 mmHg, and systemic resistance (exclusive of the coronary bed) had
      increased from 0.047 to 0.075 mmHg.min(-1).ml(-1), whereas placental resistance
      had increased from 0.065 to 0.111 mmHg.min(-1).ml(-1). Fetal plasma renin
      activities fell as early as 1 day after the start of infusion and remained below
      control (all changes P < 0.05). All flows decreased slightly although these
      decreases were not statistically significant. Thus the increase in arterial
      pressure was entirely due to an increase in systemic and placental resistances.

PMID- 16905602
TI  - Progressive epicardial coronary blood flow reduction fails to produce ST-segment
      depression at normal heart rates.
AB  - ST-segment depression is commonly seen in patients with acute coronary syndromes.
      Most authors have attributed it to transient reductions in coronary blood flow
      due to nonocclusive thrombus formation on a disrupted atherosclerotic plaque and
      dynamic focal vasospasm at the site of coronary artery stenosis. However, ST
      segment depression was never reproduced in classic animal models of coronary
      stenosis without the presence of tachycardia. We hypothesized that ST-segment
      depression occurring during acute coronary syndromes is not entirely explained by
      changes in epicardial coronary artery resistance and thus evaluated the effect of
      a slow, progressive epicardial coronary artery occlusion on the ECG and regional
      myocardial blood flow in anesthetized pigs. Slow, progressive occlusion over 72
      min (SD 27) of the left anterior descending coronary artery in 20 anesthetized
      pigs led to a 90% decrease in coronary blood flow and the development of ST
      segment elevation associated with homogeneous and transmural myocardial blood
      flow reductions, confirmed by microspheres and myocardial contrast
      echocardiography. ST-segment depression was not observed in any ECG lead before
      the development of ST-segment elevation. At normal heart rates, progressive
      epicardial stenosis of a coronary artery results in myocardial ischemia
      associated with homogeneous, transmural reduction in regional myocardial blood
      flow and ST-segment elevation, without preceding ST-segment depression. Thus, in
      coronary syndromes with ST-segment depression and predominant subendocardial
      ischemia, factors other than mere increases in epicardial coronary resistance
      must be invoked to explain the heterogeneous parietal distribution of flow and
      associated ECG changes.

PMID- 16905603
TI  - Comparative calorimetric and spectroscopic studies of the effects of lanosterol
      and cholesterol on the thermotropic phase behavior and organization of
      dipalmitoylphosphatidylcholine bilayer membranes.
AB  - We carried out comparative DSC and Fourier transform infrared spectroscopic
      studies of the effects of cholesterol and lanosterol on the thermotropic phase
      behavior and organization of DPPC bilayers. Lanosterol is the biosynthetic
      precursor of cholesterol and differs in having three rather than two axial methyl
      groups projecting from the beta-face of the planar steroid ring system and one
      axial methyl group projecting from the alpha-face, whereas cholesterol has none.
      Our DSC studies indicate that the incorporation of lanosterol is more effective
      than cholesterol is in reducing the enthalpy of the pretransition. Lanosterol is
      also initially more effective than cholesterol in reducing the enthalpies of both
      the sharp and broad components of the main phase transition. However, at sterol
      concentrations of 50 mol %, lanosterol does not abolish the cooperative
      hydrocarbon chain-melting phase transition as does cholesterol. Moreover, at
      higher lanosterol concentrations ( approximately 30-50 mol %), both sharp and
      broad low-temperature endotherms appear in the DSC heating scans, suggestive of
      the formation of lanosterol crystallites, and of the lateral phase separation of
      lanosterol-enriched phospholipid domains, respectively, at low temperatures,
      whereas such behavior is not observed with cholesterol at comparable
      concentrations. Our Fourier transform infrared spectroscopic studies demonstrate
      that lanosterol incorporation produces a less tightly packed bilayer than does
      cholesterol, which is characterized by increased hydration in the glycerol
      backbone region of the DPPC bilayer. These and other results indicate that
      lanosterol is less miscible in DPPC bilayers than is cholesterol, but perturbs
      their organization to a greater extent, probably due primarily to the rougher
      faces and larger cross-sectional area of the lanosterol molecule and perhaps
      secondarily to its decreased ability to form hydrogen bonds with adjacent DPPC
      molecules. Nevertheless, lanosterol does appear to produce a lamellar liquid
      ordered phase in DPPC bilayers, although this phase is not as tightly packed as
      comparable cholesterol/DPPC mixtures.

PMID- 16905604
TI  - Matrix protein microarrays for spatially and compositionally controlled microspot
      thrombosis under laminar flow.
AB  - Microarraying allows the spatial and compositional control of surfaces, typically
      for the purpose of binding reactions. Collagen and/or von Willebrand Factor (vWF)
      in 5% glycerol was contact printed onto glass slides to create defined microspots
      (176-microm diameter) of adsorbed protein without sample dehydration. The arrays
      were mounted on flow chambers allowing video microscopy during perfusion (wall
      shear rate of 100-500 s(-1)) of recalcified corn trypsin inhibitor-treated whole
      blood or platelet rich plasma and subsequent array scanning via anti-GPIbalpha
      and anti-fibrin(ogen) immunofluorescence. To mimic the subendothelial matrix, vWF
      was microarrayed over sonicated type I collagen microspots. For whole blood
      perfusion (500 s(-1), 10 min) over collagen, vWF, and collagen/vWF microspots,
      the amount of platelet deposition on the collagen/vWF spots was approximately 2
      times greater in comparison to the collagen spots and approximately 18 times
      greater in comparison to the vWF spots. The amount of fibrin(ogen) deposition on
      the collagen/vWF spots was approximately 2 times greater in comparison to the
      collagen spots and approximately 4 times greater in comparison to the vWF spots.
      This protocol allowed for highly uniform (CV = 18%) and precisely located
      thrombus formation at a density of >or=400 spots/cm(2). Microarrays are ideal for
      the combinatorial assembly of adhesive and procoagulant proteins to study
      thrombosis as well as to study axial and lateral transport effects between
      discrete microspots of distinct composition.

PMID- 16905605
TI  - Purinergic junctional transmission and propagation of calcium waves in spinal
      cord astrocyte networks.
AB  - Micro-photolithographic methods have been employed to form discrete patterns of
      spinal cord astrocytes that allow quantitative measurements of Ca(2+) wave
      propagation. Astrocytes were confined to lanes 20-100 microm wide and Ca(2+)
      waves propagated from a point of mechanical stimulation or of application of
      adenosine triphosphate; all Ca(2+) wave propagation was blocked by simultaneous
      application of purinergic P2Y(1) and P2Y(2) antagonists. Stimulation of an
      astrocyte at one end of a lane, followed by further stimulation of this
      astrocyte, gave rise to Ca(2+) transients in the same astrocytes; however, if the
      second stimulation was applied to an astrocyte at the other end of the lane, then
      this gave rise to a different but overlapping set of astrocytes generating a
      Ca(2+) signal. Both the amplitude and velocity of the Ca(2+) wave decreased over
      270 microm from the point of initiation, and thereafter remained, on average,
      constant with random variations for at least a further 350 microm. Also, the
      percentage of astrocytes that gave a Ca(2+) transient decreased with distance
      along lanes. All the above observations were quantitatively predicted by our
      recent theoretical model of purinergic junctional transmission, as was the Ca(2+)
      wave propagation along and between parallel lanes of astrocytes different
      distances apart. These observations show that a model in which the main
      determinants are the diffusion of adenosine triphosphates regeneratively released
      from a stimulated astrocyte, together with differences in the properties and
      density of the purinergic P2Y receptors on astrocytes, is adequate to predict a
      wide range of Ca(2+) wave transmission and propagation phenomena.

PMID- 16905606
TI  - Kinetics of the formation and dissociation of actin filament branches mediated by
      Arp2/3 complex.
AB  - The actin filament network at the leading edge of motile cells relies on
      localized branching by Arp2/3 complex from "mother" filaments growing near the
      plasma membrane. The nucleotide bound to the mother filaments (ATP, ADP and
      phosphate, or ADP) may influence the branch dynamics. To determine the effect of
      the nucleotide bound to the subunits of the mother filament on the formation and
      stability of branches, we compared the time courses of actin polymerization in
      bulk samples measured using the fluorescence of pyrene actin with observations of
      single filaments by total internal reflection fluorescence microscopy. Although
      the branch nucleation rate in bulk samples was nearly the same regardless of the
      nucleotide on the mother filaments, we observed fewer branches by microscopy on
      ADP-bound filaments than on ADP-P(i)-bound filaments. Observation of branches in
      the microscope depends on their binding to the slide. Since the probability that
      a branch binds to the slide is directly related to its lifetime, we used counts
      of branches to infer their rates of dissociation from mother filaments. We
      conclude that the nucleotide on the mother filament does not affect the initial
      branching event but that branches are an order of magnitude more stable on the
      sides of new ATP- or ADP-P(i) filaments than on ADP-actin filaments.

PMID- 16905607
TI  - Extracting dwell time sequences from processive molecular motor data.
AB  - Processive molecular motors, such as kinesin, myosin, or dynein, convert chemical
      energy into mechanical energy by hydrolyzing ATP. The mechanical energy is used
      for moving in discrete steps along the cytoskeleton and carrying a molecular
      load. Single-molecule recordings of motor position along a substrate polymer
      appear as a stochastic staircase. Recordings of other single molecules, such as
      F1-ATPase, RNA polymerase, or topoisomerase, have the same appearance. We present
      a maximum likelihood algorithm that extracts the dwell time sequence from noisy
      data, and estimates state transition probabilities and the distribution of the
      motor step size. The algorithm can handle models with uniform or alternating step
      sizes, and reversible or irreversible kinetics. A periodic Markov model describes
      the repetitive chemistry of the motor, and a Kalman filter allows one to include
      models with variable step size and to correct for baseline drift. The data are
      optimized recursively and globally over single or multiple data sets, making the
      results objective over the full scale of the data. Local binary algorithms, such
      as the t-test, do not represent the behavior of the whole data set. Our method is
      model-based, and allows rapid testing of different models by comparing the
      likelihood scores. From data obtained with current technology, steps as small as
      8 nm can be resolved and analyzed with our method. The kinetic consequences of
      the extracted dwell sequence can be further analyzed in detail. We show results
      from analyzing simulated and experimental kinesin and myosin motor data. The
      algorithm is implemented in the free QuB software.

PMID- 16905608
TI  - Stretching the immunoglobulin 27 domain of the titin protein: the dynamic energy
      landscape.
AB  - Molecular simulations are carried out on the Immunoglobulin 27 domain of the
      titin protein. The energy landscape is mapped out using an implicit solvent
      model, and molecular dynamics simulations are run with the solvent explicitly
      modeled. Stretching a protein is shown to produce a dynamic energy landscape in
      which the energy minima move in configuration space, change in depth, and are
      created and destroyed. The connections of these landscape changes to the
      mechanical unfolding of the Immunoglobulin 27 domain are addressed. Hydrogen
      bonds break upon stretching by either intrabasin processes associated with the
      movement of energy minima, or interbasin processes associated with transitions
      between energy minima. Intrabasin changes are reversible and dominate for
      flexible interactions, whereas interbasin changes are irreversible and dominate
      for stiff interactions. The most flexible interactions are Glu-Lys salt bridges,
      which can act like tethers to bind strands even after all backbone interactions
      between the strands have been broken. As the protein is stretched, different
      types of structures become the lowest energy structures, including structures
      that incorporate nonnative hydrogen bonds. Structures that have flat energy
      versus elongation profiles become the lowest energy structures at elongations of
      several Angstroms, and are associated with the unfolding intermediate state
      observed experimentally.

PMID- 16905609
TI  - Heterogeneity of early intermediates in cell-liposome fusion mediated by
      influenza hemagglutinin.
AB  - To explore early intermediates in membrane fusion mediated by influenza virus
      hemagglutinin (HA) and their dependence on the composition of the target
      membrane, we studied lipid mixing between HA-expressing cells and liposomes
      containing phosphatidylcholine (PC) with different hydrocarbon chains. For all
      tested compositions, our results indicate the existence of at least two types of
      intermediates, which differ in their lifetimes. The composition of the target
      membrane affects the stability of fusion intermediates at a stage before lipid
      mixing. For less fusogenic distearoyl PC-containing liposomes at 4 degrees C,
      some of the intermediates inactivate, and no intermediates advance to lipid
      mixing. Fusion intermediates that formed for the more fusogenic dioleoyl PC
      containing liposomes did not inactivate and even yielded partial lipid mixing at
      4 degrees C. Thus, a more fusogenic target membrane effectively blocks
      nonproductive release of the conformational energy of HA. Even for the same
      liposome composition, HA forms two types of fusion intermediates, dissimilar in
      their stability and propensity to fuse. This diversity of fusion intermediates
      emphasizes the importance of local membrane composition and local protein
      concentration in fusion of heterogeneous biological membranes.

PMID- 16905610
TI  - Structural analysis of nanoscale self-assembled discoidal lipid bilayers by solid
      state NMR spectroscopy.
AB  - Nanodiscs are an example of discoidal nanoscale self-assembled lipid/protein
      particles similar to nascent high-density lipoproteins, which reduce the risk of
      coronary artery disease. The major protein component of high-density lipoproteins
      is human apolipoprotein A-I, and the corresponding protein component of Nanodiscs
      is membrane scaffold protein 1 (MSP1), a 200-residue lipid-binding domain of
      human apolipoprotein A-I. Here we present magic-angle spinning (MAS) solid-state
      NMR studies of uniformly (13)C,(15)N-labeled MSP1 in polyethylene glycol
      precipitated Nanodiscs. Two-dimensional MAS (13)C-(13)C correlation spectra show
      excellent microscopic order of MSP1 in precipitated Nanodiscs. Secondary
      isotropic chemical shifts throughout the protein are consistent with a
      predominantly helical structure. Moreover, the backbone conformations of prolines
      derived from their (13)C chemical shifts are consistent with the molecular belt
      model but not the picket fence model of lipid-bound MSP1. Overall comparison of
      experimental spectra and (13)C chemical shifts predicted from several structural
      models also favors the belt model. Our study thus supports the belt model of
      Nanodisc structure and demonstrates the utility of MAS NMR to study the structure
      of high molecular weight lipid-protein complexes.

PMID- 16905611
TI  - Structural characterization of the binding of Myosin*ADP*Pi to actin in
      permeabilized rabbit psoas muscle.
AB  - When myosin is attached to actin in a muscle cell, various structures in the
      filaments are formed. The two strongly bound states (A*M*ADP and A*M) and the
      weakly bound A*M*ATP states are reasonably well understood. The orientation of
      the strongly bound myosin heads is uniform ("stereospecific" attachment), and the
      attached heads exhibit little spatial fluctuation. In the prehydrolysis weakly
      bound A*M*ATP state, the orientations of the attached myosin heads assume a wide
      range of azimuthal and axial angles, indicating considerable flexibility in the
      myosin head. The structure of the other weakly bound state, A*M*ADP*P(i),
      however, is poorly understood. This state is thought to be the critical pre-power
      stroke state, poised to make the transition to the strongly binding, force
      generating states, and hence it is of particular interest for understanding the
      mechanism of contraction. However, because of the low affinity between myosin and
      actin in the A*M*ADP*P(i) state, the structure of this state has eluded
      determination both in isolated form and in muscle cells. With the knowledge
      recently gained in the structures of the weakly binding M*ATP, M*ADP*P(i) states
      and the weakly attached A*M*ATP state in muscle fibers, it is now feasible to
      delineate the in vivo structure of the attached state of A*M*ADP*P(i). The series
      of experiments presented in this article were carried out under relaxing
      conditions at 25 degrees C, where approximately 95% of the myosin heads in the
      skinned rabbit psoas muscle contain the hydrolysis products. The affinity for
      actin is enhanced by adding polyethylene glycol (PEG) or by lowering the ionic
      strength in the bathing solution. Solution kinetics and binding constants were
      determined in the presence and in the absence of PEG. When the binding between
      actin and myosin was increased, both the myosin layer lines and the actin layer
      lines increased in intensity, but the intensity profiles did not change. The
      configuration (mode) of attachment in the A*M*ADP*P(i) state is thus unique among
      the intermediate attached states of the cross-bridge ATP hydrolysis cycle. One of
      the simplest explanations is that both myosin filaments and actin filaments are
      stabilized (e.g., undergo reduced spatial fluctuations) by the attachment. The
      alignment of the myosin heads in the thick filaments and the alignment of the
      actin monomers in the thin filaments are improved as a result. The compact atomic
      structure of M*ADP*P(i) with strongly coupled domains may contribute to the
      unique attachment configuration: the "primed" myosin heads may function as
      "transient struts" when attached to the thin filaments.

PMID- 16905612
TI  - Protein translocation by bacterial toxin channels: a comparison of diphtheria
      toxin and colicin Ia.
AB  - Regions of both colicin Ia and diphtheria toxin N-terminal to the channel-forming
      domains can be translocated across planar phospholipid bilayer membranes. In this
      article we show that the translocation pathway of diphtheria toxin allows much
      larger molecules to be translocated than does the translocation pathway of
      colicin Ia. In particular, the folded A chain of diphtheria toxin is readily
      translocated by that toxin but is not translocated by colicin Ia. This difference
      cannot be attributed to specific recognition of the A chain by diphtheria toxin's
      translocation pathway because the translocation pathway also accommodates folded
      myoglobin.

PMID- 16905613
TI  - Thermodynamic stability of beta-peptide helices and the role of cyclic residues.
AB  - Beta-peptides are emerging as an attractive class of peptidomimetic molecules. In
      contrast to naturally occurring alpha-peptides, short oligomers of beta-amino
      acids (comprising just 4-6 monomers) exhibit stable secondary structures that
      make them amenable for quantitative, concerted experimental and theoretical
      studies of the effects of particular chemical interactions on structure. In this
      work, molecular simulations are used to study the thermodynamic stability of
      helical conformations formed by beta-peptides containing varying proportions of
      acyclic (beta(3)) and cyclic (ACH) residues. More specifically, several beta
      peptides differing only in their content of cyclic residues are considered in
      this work. Previous computational studies of beta-peptides have relied mostly on
      energy minimization of molecular dynamics simulations. In contrast, our study
      relies on density-of-states based Monte Carlo simulations to calculate the free
      energy and examine the stability of various folded structures of these molecules
      along a well-defined order parameter. By resorting to an expanded-ensemble
      formalism, we are able to determine the free energy required to unfold specific
      molecules, a quantity that could be measured directly through single-molecule
      force spectroscopy. Simulations in both implicit and explicit solvents have
      permitted a systematic study of the role of cyclic residues and electrostatics on
      the stability of secondary structures. The molecules considered in this work are
      shown to exhibit stable H-14 helical conformations and, in some cases, relatively
      stable H-12 conformations, thereby suggesting that solvent quality may be used to
      manipulate the hydrogen-bonding patterns and structure of these peptides.

PMID- 16905614
TI  - Transbilayer effects of raft-like lipid domains in asymmetric planar bilayers
      measured by single molecule tracking.
AB  - Cell membranes have complex lipid compositions, including an asymmetric
      distribution of phospholipids between the opposing leaflets of the bilayer.
      Although it has been demonstrated that the lipid composition of the outer leaflet
      of the plasma membrane is sufficient for the formation of raft-like liquid
      ordered (l(o)) phase domains, the influence that such domains may have on the
      lipids and proteins of the inner leaflet remains unknown. We used tethered
      polymer supports and a combined Langmuir-Blodgett/vesicle fusion (LB/VF)
      technique to build asymmetric planar bilayers that mimic plasma membrane
      asymmetry in many ways. We show that directly supported LB monolayers containing
      cholesterol-rich l(o) phases are inherently unstable when exposed to water or
      vesicle suspensions. However, tethering the LB monolayer to the solid support
      with the lipid-anchored polymer 1,2-dimyristoyl phophatidylethanolamine-N
      [poly(ethylene glycol)-triethoxysilane] significantly improves stability and
      allows for the formation of complex planar-supported bilayers that retain >90%
      asymmetry for 1-2 h. We developed a single molecule tracking (SPT) system for the
      study of lipid diffusion in asymmetric bilayers with coexisting liquid phases.
      SPT allowed us to study in detail the diffusion of individual lipids inside,
      outside, or directly opposed to l(o) phase domains. We show here that l(o) phase
      domains in one monolayer of an asymmetric bilayer do not induce the formation of
      domains in the opposite leaflet when this leaflet is composed of palmitoyl-oleoyl
      phosphatidylcholine and cholesterol but do induce domains when this leaflet is
      composed of porcine brain phosphatidylcholine, phosphatidylethanolamine,
      phosphatidylserine, and cholesterol. The diffusion of lipids is similar in l(o)
      and liquid-disordered phase domains and is not affected by transbilayer coupling,
      indicating that lateral and transverse lipid interactions that give rise to the
      domain structure are weak in the biological lipid mixtures that were employed in
      this work.

PMID- 16905615
TI  - Motional restrictions of membrane proteins: a site-directed spin labeling study.
AB  - Site-directed mutagenesis was used to produce 27 single cysteine mutants of
      bacteriophage M13 major coat protein spanning the whole primary sequence of the
      protein. Single-cysteine mutants were labeled with nitroxide spin labels and
      incorporated into phospholipid bilayers with increasing acyl chain length. The
      SDSL is combined with ESR and CD spectroscopy. CD spectroscopy provided
      information about the overall protein conformation in different mismatching
      lipids. The spin label ESR spectra were analyzed in terms of a new spectral
      simulation approach based on hybrid evolutionary optimization and solution
      condensation. This method gives the residue-level free rotational space (i.e.,
      the effective space within which the spin label can wobble) and the diffusion
      constant of the spin label attached to the protein. The results suggest that the
      coat protein has a large structural flexibility, which facilitates a stable
      protein-to-membrane association in lipid bilayers with various degrees of
      hydrophobic mismatch.

PMID- 16905616
TI  - Pore characteristics of nontypeable Haemophilus influenzae outer membrane protein
      P5 in planar lipid bilayers.
AB  - The structure of outer membrane protein P5 of NTHi, a homolog of Escherichia coli
      OmpA, was investigated by observing its pore characteristics in planar lipid
      bilayers. Recombinant NTHi P5 was overexpressed in E. coli and purified using
      ionic detergent, LDS-P5, or nonionic detergent, OG-P5. LDS-P5 and OG-P5 could not
      be distinguished by their migration on SDS-PAGE gels; however, when incorporated
      into planar bilayers of DPhPC between symmetric aqueous solutions of 1 M KCl at
      22 degrees C, LDS-P5 formed narrow pores (58 +/- 6 pS) with low open probability,
      whereas OG-P5 formed large pores (1.1 +/- 0.1 nS) with high open probability
      (0.99). LDS-P5 narrow pores were gradually and irreversibly transformed into
      large pores, indistinguishable from those formed by OG-P5, at temperatures >or=40
      degrees C; the process took 4-6 h at 40 degrees C or 35-45 min at 42 degrees C.
      Large pores were stable to changes in temperatures; however, large pores were
      rapidly converted to narrow pores when exposed to LDS at room temperatures,
      indicating acute sensitivity of this conformer to ionic detergent. These studies
      suggest that narrow pores are partially denatured forms and support the premise
      that the native conformation of NTHi P5 is that of a large monomeric pore.

PMID- 16905617
TI  - A mechanical force contributes to the "osmotic swelling" of brush-border membrane
      vesicles.
AB  - Brush-border membrane vesicles and an osmotic swelling assay have been used
      extensively to monitor the pore-forming activity of Bacillus thuringiensis
      toxins. After a hypertonic shock, Manduca sexta midgut brush-border membrane
      vesicles shrink rapidly and reswell partially to a volume that depends on
      membrane permeability and toxin concentration rather than regaining their
      original volume as expected from theoretical models. Because efflux of buffer
      from the vesicles, as they shrink, could contribute to this phenomenon, vesicles
      were mixed with a hypertonic solution of the buffer with which they were loaded.
      Under these conditions, they are not expected to reswell, since the same solute
      is present on both sides of the membrane. Nevertheless, with several buffers,
      vesicles reswelled readily, an observation that demonstrates the involvement of
      an additional restoration force. Reswelling also occurred when, in the absence of
      toxin, the buffers were replaced by glucose, a solute that diffuses readily
      across the membrane, but did not occur with rat liver microsomes, despite their
      permeability to glucose. Unexpected swelling was also observed with rabbit
      jejunum brush-border membrane vesicles, suggesting that the cytoskeleton, present
      in brush-border membrane vesicles but absent from microsomes, could be
      responsible for the restoration force.

PMID- 16905618
TI  - Enantioselective substrate binding in a monooxygenase protein model by molecular
      dynamics and docking.
AB  - The two-component flavoenzyme styrene monooxygenase (SMO) is an efficient
      alternative to several chemical epoxidation catalysts on a preparative scale. A
      first homology model of the catalytic domain (StyA) of SMO was constructed
      (Protein Data Bank ID 2HD8) based on the structure of para-hydroxybenzoate
      hydroxylase. The StyA protein structure was optimized by restrained molecular
      dynamics to reproduce specific pre-S binding orientations of styrene. Effects of
      all 10 point mutations examined were explained by the distance of the site to the
      styrene and FAD binding sites. Thirteen of 20 ligands could be accommodated in a
      catalytically active binding orientation, and predicted affinities correlated
      well with experimental turnover and inhibition. The binding cavity is almost
      completely hydrophobic except for a hydrogen-bonded network formed by three water
      molecules, the backbone of residues 300-302, and the flavin ribityl, similar to
      P293, and three crystal waters in para-hydroxybenzoate hydroxylase suggest that
      P302, T47, and the waters in StyA are a vital component of the catalytic
      mechanism. The current optimized and validated StyA model provides a good
      starting point for elucidation of the structural basis of StyA ligand binding and
      catalysis. Novel insights in the binding of ligands to SMO/StyA, provided by the
      current protein model, will aid the rational design of mutants with specific,
      altered enantioselective properties.

PMID- 16905619
TI  - Out and in: simplifying membrane protein studies by AFM.

PMID- 16905620
TI  - High-resolution AFM of membrane proteins directly incorporated at high density in
      planar lipid bilayer.
AB  - The heterologous expression and purification of membrane proteins represent major
      limitations for their functional and structural analysis. Here we describe a new
      method of incorporation of transmembrane proteins in planar lipid bilayer
      starting from 1 pmol of solubilized proteins. The principle relies on the direct
      incorporation of solubilized proteins into a preformed planar lipid bilayer
      destabilized by dodecyl-beta-maltoside or dodecyl-beta-thiomaltoside, two
      detergents widely used in membrane biochemistry. Successful incorporations are
      reported at 20 degrees C and at 4 degrees C with three bacterial photosynthetic
      multi-subunit membrane proteins. Height measurements by atomic force microscopy
      (AFM) of the extramembraneous domains protruding from the bilayer demonstrate
      that proteins are unidirectionally incorporated within the lipid bilayer through
      their more hydrophobic domains. Proteins are incorporated at high density into
      the bilayer and on incubation diffuse and segregate into protein close-packing
      areas. The high protein density allows high-resolution AFM topographs to be
      recorded and protein subunits organization delineated. This approach provides an
      alternative experimental platform to the classical methods of two-dimensional
      crystallization of membrane proteins for the structural analysis by AFM.
      Furthermore, the versatility and simplicity of the method are important intrinsic
      properties for the conception of biosensors and nanobiomaterials involving
      membrane proteins.

PMID- 16905621
TI  - Conservative treatment of work-related upper limb disorders: a review.
AB  - AIM: The literature review was carried out to identify and summarize the evidence
      base for conservative clinical management of upper limb disorders (ULDs)
      including specific disorders and non-specific ULDs. METHOD: Keywords were
      identified through a scoping study and guidance from the project sponsor. A
      number of databases were searched including Web of Knowledge, Pub Med, Medline,
      Ergonomics Online, the Cochrane Library and BMJ Clinical Evidence for the years
      1993-2004. Abstracts were obtained for papers identified in the search and full
      papers were obtained for literature, which included diagnostic methods,
      conservative treatments, new data or results or systematic reviews. RESULTS: The
      review identified that there is evidence for the efficacy of conservative
      treatments for the management of carpal tunnel syndrome, epicondylitis, rotator
      cuff tendonitis and bicipital tendonitis and tension neck syndrome. There was no
      evidence found to support or refute conservative treatment of tenosynovitis,
      tendonitis, de Quervain's disease or diffuse non-specific ULDs. CONCLUSION: The
      evidence reviewed was not always of good quality and data gaps including
      methodological design issues need to be addressed by future research.

PMID- 16905622
TI  - A meta-analysis of occupational trichloroethylene exposure and multiple myeloma
      or leukaemia.
AB  - BACKGROUND: Trichloroethylene (TCE) has been widely used as an industrial solvent
      and degreasing agent. AIMS: We conducted a meta-analysis of epidemiologic studies
      of occupational TCE exposure and multiple myeloma (MM) or leukaemia. METHODS: We
      identified a total of eight cohort or case-control studies that enumerated a TCE
      exposed study population and presented relative risk (RR) estimates for MM (n =
      7) and/or leukaemia (n = 7). The individual studies included aerospace or
      aircraft workers (n = 3 studies), workers from a transformer manufacturing plant
      (n = 1 study) and workers from numerous occupations who, based on biomonitoring
      or extensive industrial hygiene exposure measurements, were likely exposed to TCE
      (n = 4). We used random effects models to calculate summary relative risk
      estimates (SRRE). In addition, we examined heterogeneity across studies and the
      relative influence of each individual study on the overall meta-analysis.
      RESULTS: No association was observed for MM (SRRE = 1.05, 95% CI: 0.80-1.38; P
      value for heterogeneity = 0.94) or leukaemia (SRRE = 1.11, 95% CI: 0.93-1.32; P
      value for heterogeneity = 0.50), based on TCE-exposed subgroup meta-analyses.
      Study-specific RR estimates for MM ranged between 0.57 and 1.62. RRs for
      leukaemia ranged between 1.05 and 1.15 in five studies, while one study reported
      a 2-fold increased RR and another study reported an inverse association of 0.60.
      All confidence intervals (CIs) for study-specific estimates included 1.0.
      CONCLUSIONS: The results of this meta-analysis do not support an etiologic
      association between occupational TCE exposure and risk of MM or leukaemia.

PMID- 16905623
TI  - Thenar hammer syndrome: a case report.
AB  - BACKGROUND: Raynaud's phenomenon occurs among automobile mechanics secondary to
      long-term use of vibrating hand-held tools. It can also occur from traumatic
      injury to the upper extremity. AIM: This report describes a case of single digit
      Raynaud's phenomenon in an automobile mechanic due to focal arterial impact
      trauma. CASE REPORT: A 38-year-old right-handed transmission mechanic complained
      of paraesthesia and blanching of the right index finger on exposure to cold and
      eventually developed a transient necrotic ulcer at the tip of the digit. He had a
      long history of occupational exposure to vibrating hand-held power tools.
      Evaluation for common causes of Raymond's phenomenon was negative. The diagnosis
      of hand-arm vibration syndrome (HAVS) was rejected because of the rapidity of
      progression and severity of the symptoms restricted only to the index finger
      without corresponding symptoms of the other digits of the right hand as would be
      expected. Angiography revealed an obstructive lesion of the distal right radial
      artery at the wrist and he was diagnosed with thenar hammer syndrome. This
      uncommon condition was due to focal injury of the distal radial artery caused by
      repeated slamming of transmission parts on a work table. CONCLUSIONS: Not all
      cases of Raynaud's phenomenon in workers using vibrating hand-held tools are due
      to HAVS. Alternative aetiologies should be considered especially if symptoms are
      asymmetrical and unilateral.

PMID- 16905624
TI  - Evaluation of a functional restoration programme in chronic low back pain.
AB  - BACKGROUND: Persistent low back pain is a major health and socio-economic problem
      in the UK. Evidence-based guidelines have been produced to inform management
      strategies for this significant health issue. This study reports the outcome of a
      tertiary intervention functional restoration programme (FRP) in manual workers of
      a water utility company, consistent with UK guidelines. OBJECTIVES: To evaluate
      whether a FRP could achieve a sustainable improvement in back health, a
      sustainable return to full duties and a cost reduction. METHOD: Participants were
      assessed at start, end, 12 and 24 months post-programme. RESULTS: Eighty-nine
      employees completed the FRP; 78 returned to normal duties, nine to restricted
      duties and two left the employer shortly after. Overall, there were significant
      improvements in psychological status, perceived pain, disability and work
      capability. Improvements were sustained for 24 months. Sickness absence and the
      need for post-treatment work restrictions decreased. Reductions in ill-health
      retirements and compensation claims for low back pain were reduced. CONCLUSION:
      The findings support the effectiveness of a tertiary intervention FRP for workers
      with persistent low back pain.

PMID- 16905625
TI  - Identifying workers at risk of sickness absence by questionnaire.
AB  - BACKGROUND: Sickness absence is an important economic problem, because of high
      costs and lost productivity. Determining factors associated with increased risk
      of sickness absence may lead to the development of preventive measures. AIMS: To
      determine whether self-report questionnaires can identify those employees at risk
      of sickness absence METHODS: Prospective study of 238 healthy administrative
      workers. Participants completed a questionnaire proven to be valid and
      consistent. The questionnaire consisted of 116 items about health, work and
      working conditions. Sickness absence was followed-up for a period of 1 year.
      RESULTS: The questionnaires of 191 workers (80%) were suitable for analysis. The
      number of reported health complaints was significantly (P < 0.01) associated with
      sickness absence (OR 2.18; 95% CI 1.32-3.61). Concentration problems were
      correlated with more frequent absences, and both nervous complaints and coping
      problems with longer duration. Age (OR 0.96; 95% CI 0.93-0.99; P = 0.02) and job
      insecurity (OR 0.68; 95% CI 0.47-0.98; P = 0.04) were negatively associated with
      sickness absence. Psychosocial and physical work factors were not associated with
      sickness absence. CONCLUSIONS: Questionnaires on health and work can identify
      employees at future risk of sickness absence. Workers who report multiple health
      complaints, especially concentration problems, nervous complaints or coping
      problems, may be at increased risk of sickness absence.

PMID- 16905626
TI  - Mechanoelectrical feedback regulates the arrhythmogenic activity of pulmonary
      veins.
AB  - BACKGROUND: Atrial fibrillation is commonly associated with dilated pulmonary
      veins. Stretch has been shown to have mechano-electrical effects. OBJECTIVE: To
      investigate whether stretch can increase the arrhythmogenic activity of the
      pulmonary veins. METHODS: The transmembrane action potentials were recorded from
      rabbit pulmonary veins before and after stretch (100 and 300 mg). Gadolinium and
      streptomycin (stretch-activated ion channel blockers) were each perfused into the
      pulmonary veins under a 300-mg stretch. RESULTS: Stretch (0, 100 and 300 mg)
      force dependently increased the incidence of spontaneous activity (22%, 48% and
      83%; p<0.05), mean (standard deviation (SD)) firing rates of spontaneous activity
      (1.7 (0.2), 2.1 (0.3) and 3 (0.2) Hz; p<0.05) and incidence of early post
      depolarisations (9%, 26% and 61%; p<0.05) and delayed post-depolarisations (0%,
      4% and 30%; p<0.05) in 23 pulmonary veins. In the seven preparations with
      spontaneous activity after the 300-mg stretch, gadolinium (1, 3 and 10 mumol/l)
      decreased the incidence of spontaneous activity by 43%, 29% and 14%, respectively
      (p<0.05), and decreased the firing rate from 2.9 (0.1) Hz to 0.8 (0.4), 0.3 (0.1)
      and 0.1 (0.1) Hz, respectively (p<0.05). Streptomycin (10 and 40 mumol/l)
      decreased the incidence of spontaneous activity by 71% and 29%, respectively
      (p<0.05), and decreased the firing rate from 2.9 (0.1) Hz to 1.6 (0.4) and 0.5
      (0.3) Hz, respectively (p<0.05). CONCLUSION: Stretch is an important factor in
      the electrical activity of the pulmonary vein. Stretch-induced arrhythmogenic
      activity of the pulmonary vein may contribute to the genesis of atrial
      fibrillation.

PMID- 16905627
TI  - Outcome after redo coronary artery bypass grafting in patients with ischaemic
      cardiomyopathy and viable myocardium.
AB  - BACKGROUND: Repeat coronary artery bypass grafting (redo-CABG) in patients with
      ischaemic cardiomyopathy is associated with high perioperative risk and worse
      long-term outcome compared with patients undergoing their first CABG. OBJECTIVE:
      To assess whether patients with viable myocardium undergoing redo-CABG have a
      better outcome. METHODS: 18 patients with ischaemic cardiomyopathy underwent redo
      CABG and 34 underwent their first CABG; all had substantial viability (> or =25%
      of the left ventricle) on dobutamine stress echocardiography (DSE). Left
      ventricular ejection fraction (LVEF) and heart failure symptoms were assessed
      before and 9-12 months after revascularisation. Cardiac event rate was assessed
      during the follow-up period (median 4 years, 25-75th centile 2.8-4.9 years).
      RESULTS: The extent of viable myocardium on DSE was comparable in the two groups
      (11.3 (3.9) segments in patients who underwent redo-CABG v 12.8 (3.0) in patients
      who underwent their first CABG; p = NS). LVEF improved from 32% (9%) to 39%
      (12%); p = 0.01, in patients who underwent redo-CABG and from 30% (7%) to 36%
      (7%); p<0.01, in those who underwent their first CABG; New York Heart Association
      class improved from 2.5 (1.1) to 1.9 (0.8); p = 0.03, and from 2.7 (1.0) to 1.8
      (0.70); p<0.01, respectively. In patients who underwent redo-CABG, the
      perioperative mortality was 0, post-surgery inotropic support was needed in 11%
      of the patients and mid-term (4-year) survival was 100%, with a total event rate
      of 28%. All these variables were not statistically different from patients who
      underwent their first CABG (p = 0.50, 0.90, 0.08 and 0.81, respectively).
      CONCLUSION: Patients with ischaemic cardiomyopathy and substantial viability
      undergoing redo-CABG benefit from revascularisation in terms of improvement in
      LVEF, heart failure symptoms, angina and mid-term prognosis.

PMID- 16905628
TI  - Oral glucose tolerance test is needed for appropriate classification of glucose
      regulation in patients with coronary artery disease: a report from the Euro Heart
      Survey on Diabetes and the Heart.
AB  - BACKGROUND: Patients with coronary artery disease (CAD) and abnormal glucose
      regulation (AGR) are at high risk for subsequent cardiovascular events,
      underlining the importance of accurate glucometabolic assessment in clinical
      practice. OBJECTIVE: To investigate different methods to identify glucose
      disturbances among patients with acute and stable coronary heart disease.
      METHODS: Consecutive patients referred to cardiologists were prospectively
      enrolled at 110 centres in 25 countries (n = 4961). Fasting plasma glucose (FPG)
      and glycaemia 2 h after a 75-g glucose load were requested in patients without
      known glucose abnormalities (n = 3362). Glucose metabolism was classified
      according to the World Health Organization and American Diabetes Association
      (ADA; 1997, 2004) criteria as normal, impaired fasting glucose (IFG), impaired
      glucose tolerance (IGT) or diabetes. RESULTS: Data on FPG and 2-h post-load
      glycaemia were available for 1867 patients, of whom 870 (47%) had normal glucose
      regulation, 87 (5%) had IFG, 591 (32%) had IGT and 319 (17%) had diabetes. If
      classification had been based on the ADA criterion from 1997, the proportion of
      misclassified (underdiagnosed) patients would have been 39%. The ADA 2004
      criterion would have overdiagnosed 8% and underdiagnosed 33% of the patients,
      resulting in a total misclassification rate of 41%. For ethical concerns and
      practical reasons, oral glucose tolerance test (OGTT) was not conducted in 1495
      of eligible patients. These patients were more often women, had higher age and
      waist circumference, and were therefore more likely to have AGR than those who
      were included. A model based on easily available clinical and laboratory
      variables, including FPG, high-density lipoprotein cholesterol, age and the
      logarithm of glycated haemoglobin A1c, misclassified 44% of the patients, of whom
      18% were overdiagnosed and 26% were underdiagnosed. CONCLUSION: An OGTT is still
      the most appropriate method for the clinical assessment of glucometabolic status
      in patients with coronary heart disease.

PMID- 16905629
TI  - Magnetic resonance myocardial perfusion imaging: a new era in the detection of
      reversible myocardial ischaemia.
AB  - In due course, magnetic resonance myocardial perfusion imaging will probably
      replace SPECT as the most widely used non-invasive method for detecting
      reversible myocardial ischaemia.

PMID- 16905630
TI  - Assessing patients' beliefs about cardiac rehabilitation as a basis for
      predicting attendance after acute myocardial infarction.
AB  - BACKGROUND: Some sociodemographic and psychological variables such as patients'
      belief about illness are associated with attendance at cardiac rehabilitation.
      Exploration of patients' beliefs about treatment regarding cardiac rehabilitation
      has been limited to qualitative studies; their role in relation to attendance at
      cardiac rehabilitation after acute myocardial infarction (AMI) remains
      speculative. OBJECTIVES: To develop a valid and reliable measure of patients'
      beliefs regarding cardiac rehabilitation and to ascertain the relationship
      between such beliefs and attendance. DESIGN: A prospective questionnaire-based
      study. SETTING: Coronary care unit of a London teaching hospital. PATIENTS: 130
      patients with AMI; 104 (83%) men; mean age 58.4 (standard deviation (SD) 10.7)
      years. INTERVENTIONS: Patients completed a 26-item questionnaire consisting of
      statements pertaining to beliefs about cardiac rehabilitation. MAIN OUTCOME
      MEASURES: Cardiac rehabilitation attendance; beliefs of patients about cardiac
      rehabilitation. RESULTS: Four subscales pertaining to patients' beliefs about
      cardiac rehabilitation were produced, accounting for 65.3% of the attendance
      variance: perceived necessity of cardiac rehabilitation (alpha = 0.71), concerns
      about exercise (alpha = 0.79), practical barriers (alpha = 0.70) and perceived
      personal suitability (alpha = 0.74). Patients who attended were more likely to
      believe that cardiac rehabilitation was necessary and to understand its role
      compared with non-attenders (17.7 (SD 2.7) v 16.9 (SD 3.0), p = 0.029). Patients
      who thought cardiac rehabilitation was suitable for a younger, more active person
      were less likely to attend (5.6 (SD 1.9) v 4.6 (SD 1.7), p = 0.007). Patients who
      expressed concerns about exercise or who reported practical barriers to
      attendance were less likely to attend, although these did not reach statistical
      significance. CONCLUSION: Beliefs about cardiac rehabilitation can be quantified
      and differ between attenders and non-attenders of cardiac rehabilitation.

PMID- 16905631
TI  - Pregnancy in women with valvular heart disease.
AB  - Patients with valvular disease who desire pregnancy or are already pregnant
      require specialised care. Ideally, women undergo preconceptual counselling that
      addresses any procedures needed to decrease the risks of pregnancy, including
      valve replacement, if the patient has symptoms at baseline. Management during
      pregnancy includes replacing any contraindicated medications with safer
      alternatives, optimising loading conditions, careful monitoring and aggressive
      treatment of any exacerbating factors. Rarely, percutaneous or surgical
      intervention is required during pregnancy. Labour and delivery often require
      invasive haemodynamic monitoring and a multi-disciplinary team for optimal
      maternal and fetal outcomes.

PMID- 16905632
TI  - Is the superior efficacy of new generation antipsychotics an artifact of LOCF?
AB  - It has been argued that the efficacy superiority found in meta-analyses for some
      of the atypical antipsychotics is an artifact of higher dropout rates due to side
      effects in the haloperidol group combined with last-observation-carried-forward
      (LOCF) analyses. We therefore reanalyzed a number of pivotal studies comparing
      new generation antipsychotics (NGAs) and conventional antipsychotics (CAs). A
      total of 5 studies (n = 1271) comparing amisulpride and 3 studies (n = 2454)
      comparing olanzapine with CAs were reanalyzed using original patient data. We
      applied 4 different models: LOCF, completer analysis, LOCF but excluding dropouts
      due to adverse events, and LOCF but excluding all dropouts with the exception of
      dropouts related to efficacy. Effect sizes expressed as standardized mean
      differences between NGAs and CAs based on the 4 different analysis models were
      compared. The overall results were not different irrespective of the model used.
      Single studies, however, showed higher effect sizes when LOCF instead of other
      models was used. Overall, it does not seem that higher dropout rates due to side
      effects in the haloperidol groups together with LOCF analyses consistently biased
      the results in favor of amisulpride and olanzapine. Because the results of the
      single studies, however, showed that this may occasionally be the case, future
      studies should look at the data from different angles applying sensitivity
      analyses, and they may use alternative statistics such as mixed models, which
      need to be developed further. Ultimately, strategies to reduce dropout rates are
      needed.

PMID- 16905633
TI  - Psychotherapy for schizophrenia in the year 2030: prognosis and prognostication.
AB  - A number of psychotherapy techniques have been developed that, to varying
      degrees, have empirical support demonstrating favorable effects in the treatment
      of schizophrenia (or serious mental illness [SMI]). These techniques, and the
      research, vary with respect to theoretical origins, format, treatment targets,
      and expected outcome. A historical perspective informs understanding of this
      proliferation. One landmark in psychotherapy research was the recognition of
      common factors: different therapies embody common therapeutic factors not central
      to any one school. Importantly, insights about common factors reflected a better
      theoretical understanding of the psychotherapy process and led to the translation
      of learning and conditioning theories into the psychotherapy vocabulary. This
      resulted in the distinction between specific and nonspecific treatment effects,
      which pose present-day research questions such as how common and specific factors
      interact, and the differentiation of techniques for specific recipients. Because
      psychotherapy research progresses over the next 25 years, it will be important to
      develop a model that can answer such questions while incorporating the
      proliferation of specific modalities and the search for the "right recipe." This
      "search" will coincide with more attention to individual differences, it will
      incorporate quantitative modeling, and it will spawn an array of "tools" for
      treating problems associated with SMI. Because self-knowledge and personhood
      again become recognized dimensions of recovery, traditional psychodynamic
      principles and techniques will be revisited. This article explicates a 4-factor
      model that may be a view to the future.

PMID- 16905634
TI  - Efficacy of psychological therapy in schizophrenia: conclusions from meta
      analyses.
AB  - Over the past years, evidence for the efficacy of psychological therapies in
      schizophrenia has been summarized in a series of meta-analyses. The present
      contribution aims to provide a descriptive survey of the evidence for the
      efficacy of psychological therapies as derived from these meta-analyses and to
      supplement them by selected findings from an own recent meta-analysis. Relevant
      meta-analyses and randomized controlled trials were identified by searching
      several electronic databases and by hand searching of reference lists. In order
      to compare the findings of the existing meta-analyses, the reported effect sizes
      were extracted and transformed into a uniform effect size measure where possible.
      For the own meta-analysis, weighted mean effect size differences between
      comparison groups regarding various types of outcomes were estimated. Their
      significance was tested by confidence intervals, and heterogeneity tests were
      applied to examine the consistency of the effects. From the available meta
      analyses, social skills training, cognitive remediation, psychoeducational coping
      oriented interventions with families and relatives, as well as cognitive
      behavioral therapy of persistent positive symptoms emerge as effective adjuncts
      to pharmacotherapy. Social skills training consistently effectuates the
      acquisition of social skills, cognitive remediation leads to short-term
      improvements in cognitive functioning, family interventions decrease relapse and
      hospitalization rates, and cognitive behavioral therapy results in a reduction of
      positive symptoms. These benefits seem to be accompanied by slight improvements
      in social functioning. However, open questions remain as to the specific
      therapeutic ingredients, to the synergistic effects, to the indication, as well
      as to the generalizability of the findings to routine care.

PMID- 16905636
TI  - Cigarette smoke upregulates pulmonary vascular matrix metalloproteinases via TNF
      alpha signaling.
AB  - Cigarette smoke exposure causes vascular remodeling and pulmonary hypertension by
      poorly understood mechanisms. To ascertain whether cigarette smoke exposure
      affects production of matrix metalloproteinases (MMPs) in the pulmonary vessels,
      we exposed C57Bl/6 (C57) mice or mice lacking TNF-alpha receptors (TNFRKO) to
      smoke daily for 2 wk or 6 mo. Using laser capture microdissection and RT-PCR
      analysis, we examined gene expression of MMP-2, MMP-9, MMP-12, MMP-13, and tissue
      inhibitor of metalloproteinase (TIMP-1) and examined protein production by
      immunohistochemistry for MMP-2, MMP-9, and MMP-12 in small intrapulmonary
      arteries. At 2 wk, mRNA levels of TIMP-1 and all MMPs were increased in the C57,
      but not TNFRKO, mice, and immunoreactive protein for MMP-2, MMP-9, and MMP-12 was
      also increased in the C57 mice. Increased gelatinase activity was identified by
      in situ and bulk tissue zymography. At 6 mo, only MMP-12 mRNA levels remained
      increased in the C57 mice, but at a much lower level; however, MMP-2 mRNA levels
      increased in the TNFRKO mice. We conclude that smoke exposure increases MMP
      production in the small intrapulmonary arteries but that, with the exception of
      MMP-12, increased MMP production is transient. MMPs probably play a role in smoke
      induced vascular remodeling, as they do in other forms of pulmonary hypertension,
      implying that MMP inhibitors might be beneficial. MMP production is largely TNF
      alpha dependent, further supporting the importance of TNF-alpha in the
      pathogenesis of cigarette smoke-induced lung disease.

PMID- 16905635
TI  - A neuropsychiatric model of biological and psychological processes in the
      remission of delusions and auditory hallucinations.
AB  - This selective review combines cognitive models and biological models of
      psychosis into a tentative integrated neuropsychiatric model. The aim of the
      model is to understand better, how pharmacotherapy and cognitive-behavior therapy
      come forward as partners in the treatment of psychosis and play complementary and
      mutually reinforcing roles. The article reviews the dominant models in
      literature. The focus in this review is on one hand on neural circuits that are
      involved in cognitive models and on the other hand on cognitive processes and
      experiences involved in biological models. In this way, a 4-component
      neuropsychiatric model is tentatively constructed: (1) a biological component
      that leads to aberrant perceptions and salience of stimuli, (2) a cognitive
      component that attempts to explain the psychic abnormal events, (3) a mediating
      component with psychological biases which influences the reasoning process in the
      direction of the formation of (secondary) delusions, and (4) a component of
      psychological processes that maintains delusions and prevents the falsification
      of delusional ideas. Remission consists actually of 2 processes. Biological
      remission consists of the dampening of mesolimbic dopamine releases with
      antipsychotic medication and decreases the continuous salient experiences.
      Psychological remission consists of the reappraisal of primary psychotic
      experiences. Both forms of remission are partially independent. We expect that a
      full remission including biological and psychological remission could prevent
      relapse.

PMID- 16905637
TI  - Lung injury after ozone exposure is iron dependent.
AB  - We tested the hypothesis that oxidative stress and biological effect after ozone
      (O3) exposure are dependent on changes in iron homeostasis. After O3 exposure,
      healthy volunteers demonstrated increased lavage concentrations of iron,
      transferrin, lactoferrin, and ferritin. In normal rats, alterations of iron
      metabolism after O3 exposure were immediate and preceded the inflammatory influx.
      To test for participation of this disruption in iron homeostasis in lung injury
      following O3 inhalation, we exposed Belgrade rats, which are functionally
      deficient in divalent metal transporter 1 (DMT1) as a means of iron uptake, and
      controls to O3. Iron homeostasis was disrupted to a greater extent and the extent
      of injury was greater in Belgrade rats than in control rats. Nonheme iron and
      ferritin concentrations were higher in human bronchial epithelial (HBE) cells
      exposed to O3 than in HBE cells exposed to filtered air. Aldehyde generation and
      IL-8 release by the HBE cells was also elevated following O3 exposure. Human
      embryonic kidney (HEK 293) cells with elevated expression of a DMT1 construct
      were exposed to filtered air and O3. With exposure to O3, elevated DMT1
      expression diminished oxidative stress (i.e., aldehyde generation) and IL-8
      release. We conclude that iron participates critically in the oxidative stress
      and biological effects after O3 exposure.

PMID- 16905638
TI  - Subcellular distribution of the TSC2 gene product tuberin in human airway smooth
      muscle cells is driven by multiple localization sequences and is cell-cycle
      dependent.
AB  - The products of the tuberous sclerosis complex (TSC) genes, hamartin and tuberin
      (TSC1 and 2), form a heteromer, which represses the kinase mammalian target of
      rapamycin. Loss of TSC1 or 2 results in diseases characterized by loss of cell
      cycle control, including TSC and lymphangioleiomyomatosis. As tuberin has
      multiple signaling inputs, including phosphatidylinositide-3-OH kinase, mitogen
      activated protein kinase, and adenosine monophosphate kinase, we postulated
      tuberin would have multiple protein interactions governed by subcellular
      localization and cellular status and examined this in primary human airway smooth
      muscle cells. Using immunofluorescence and confocal microscopy, tuberin was
      detected in cytoplasm, nucleus, nucleoli, and mitochondria. Fractionation of
      synchronized airway smooth cells showed that tuberin enters the nucleus in late
      G(1), and passage through the cell cycle is necessary for nuclear entry. Deletion
      constructs showed localization sequences for the nucleus between amino acids 1351
      and 1807, for mitochondria between 901 and 1350, and for cytoplasmic speckles
      between 1 and 450. Using fluorophore-tagged proteins, we observed fluorescence
      resonance energy transfer between tuberin and hamartin within these speckles,
      indicating a direct interaction between the proteins at this site. The
      observations that tuberin is localized to mitochondria and translocated to the
      nucleus in G(1) are novel and consistent with interactions with proteins within
      multiple signaling pathways. Dynamic relocalization of tuberin may control these
      interactions to integrate these pathways. As tuberin has potential roles in
      proliferation, migration, and cell phenotype, it therefore warrants further
      investigation in diseases categorized by abnormalities in airway smooth muscle.

PMID- 16905639
TI  - Altered allergen-induced eosinophil trafficking and physiological dysfunction in
      airways with preexisting virus-induced injury.
AB  - Although both asthmatics and allergic rhinitics develop an acute inflammatory
      response to lower airway allergen challenge, only asthmatics experience airway
      obstruction resulting from chronic environmental allergen exposure. Hypothesizing
      that asthmatic airways have an altered response to chronic allergic inflammation,
      we compared the effects of repeated low-level exposures to inhaled Alternaria
      extract in sensitized rats with preexisting chronic postbronchiolitis airway
      dysfunction versus sensitized controls with normal airways. Measurements of air
      space (bronchoalveolar lavage) inflammatory cells, airway goblet cells, airway
      wall collagen, airway wall eosinophils, airway alveolar attachments, and
      pulmonary physiology were conducted after six weekly exposures to aerosolized
      saline or Alternaria extract. Postbronchiolitis rats, but not those starting with
      normal airways, had persistent increases in airway wall eosinophils, goblet cell
      hyperplasia in small airways, and loss of lung elastic recoil after repeated
      exposure to aerosolized Alternaria extract. Despite having elevated airway wall
      eosinophils, the postbronchiolitis rats had no eosinophils in bronchoalveolar
      lavage at 5 days after the last allergen exposure, suggesting altered egression
      of tissue eosinophils into the air space. In conclusion, rats with preexisting
      airway pathology had altered eosinophil trafficking and allergen-induced changes
      in airway epithelium and lung mechanics that were absent in sensitized control
      rats that had normal airways before the allergen exposures.

PMID- 16905640
TI  - Sulforaphane-stimulated phase II enzyme induction inhibits cytokine production by
      airway epithelial cells stimulated with diesel extract.
AB  - Airborne particulate pollutants, such as diesel exhaust particles, are thought to
      exacerbate lung and cardiovascular diseases through induction of oxidative
      stress. Sulforaphane, derived from cruciferous vegetables, is the most potent
      known inducer of phase II enzymes involved in the detoxification of xenobiotics.
      We postulated that sulforaphane may be able to ameliorate the adverse effects of
      pollutants by upregulating expression of endogenous antioxidant enzymes.
      Stimulation of bronchial epithelial cells with the chemical constituents of
      diesel particles result in the production of proinflammatory cytokines. We first
      demonstrated a role for phase II enzymes in regulating diesel effects by
      transfecting the airway epithelial cell line (BEAS-2B) with the sentinel phase II
      enzyme NAD(P)H: quinine oxidoreductase 1 (NQO1). IL-8 production in response to
      diesel extract was significantly reduced in these compared with untransfected
      cells. We then examined whether sulforaphane would stimulate phase II induction
      and whether this would thereby ablate the effect of diesel extracts on cytokine
      production. We verified that sulforaphane significantly augmented expression of
      the phase II enzyme genes GSTM1 and NQO1 and confirmed that sulforaphane
      treatment increased glutathione S-transferase activity in epithelial cells
      without inducing cell death or apoptosis. Sulforaphane pretreatment inhibited IL
      8 production by BEAS-2B cells upon stimulation with diesel extract. Similarly,
      whereas diesel extract stimulated production of IL-8, granulocyte-macrophage
      colony-stimulating factor, and IL-1beta from primary human bronchial epithelial
      cells, sulforaphane pretreatment inhibited diesel-induced production of all of
      these cytokines. Our studies show that sulforaphane can mitigate the effect of
      diesel in respiratory epithelial cells and demonstrate the chemopreventative
      potential of phase II enzyme enhancement.

PMID- 16905641
TI  - Proteasome dysfunction inhibits surfactant protein gene expression in lung
      epithelial cells: mechanism of inhibition of SP-B gene expression.
AB  - Surfactant proteins maintain lung function through their actions to reduce
      alveolar surface tension and control of innate immune responses in the lung. The
      ubiquitin proteasome pathway is responsible for the degradation of majority of
      intracellular proteins in eukaryotic cells, and proteasome dysfunction has been
      linked to the development of neurodegenerative, cardiac, and other diseases.
      Proteasome function is impaired in interstitial lung diseases associated with
      surfactant protein C (SP-C) mutation mapping to the BRICHOS domain located in the
      proSP-C protein. In this study we determined the effects of proteasome inhibition
      on surfactant protein expression in H441 and MLE-12 lung epithelial cells to
      understand the relationship between proteasome dysfunction and surfactant protein
      gene expression. Proteasome inhibitors lactacystin and MG132 reduced the levels
      of SP-A, SP-B, and SP-C mRNAs in a concentration-dependent manner in H441 and MLE
      12 cells. In H441 cells, lactacystin and MG132 inhibition of SP-B mRNA was
      associated with similar decreases in SP-B protein, and the inhibition was due to
      inhibition of gene transcription. Proteasome inhibitors decreased thyroid
      transcription factor-1 (TTF-1)/Nkx2.1 DNA binding activity, and the reduced TTF-1
      DNA binding activity was due to reduced expression levels of TTF-1 protein. These
      data indicated that the ubiquitin proteasome pathway is essential for the
      maintenance of surfactant protein gene expression and that disruption of this
      pathway inhibits surfactant protein gene expression via reduced expression of TTF
      1 protein.

PMID- 16905642
TI  - Serum cholesterol levels and the risk of Parkinson's disease.
AB  - Several recent findings suggest a role of lipid and cholesterol metabolism in the
      pathogenesis of Parkinson's disease. Therefore, the authors examined the
      association between serum levels of cholesterol and the risk of Parkinson's
      disease in the prospective, population-based Rotterdam Study among 6,465 subjects
      aged 55 or more years with repeated in-person examination and on average 9.4
      years of follow-up (1990-2004). Higher serum levels of total cholesterol were
      associated with a significantly decreased risk of Parkinson's disease (age- and
      sex-adjusted hazard ratio per mmol/liter increase in cholesterol = 0.77, 95%
      confidence interval: 0.64, 0.94), with evidence for a dose-effect relation. The
      association was restricted to women and remained unchanged after adjustment for
      multiple potential confounders. These findings may indicate a role of lipids in
      the pathogenesis of Parkinson's disease. Alternatively, they could reflect the
      strong correlation-especially in women-between levels of serum cholesterol and
      the antioxidant coenzyme Q10. If confirmed, this would provide further support
      for an important role of oxidative stress in the pathogenesis of Parkinson's
      disease.

PMID- 16905643
TI  - Protective association between nonsteroidal antiinflammatory drug use and
      measures of benign prostatic hyperplasia.
AB  - In 1990-2002, the authors conducted a population-based cohort study of 2,447
      Caucasian men in Olmsted County, Minnesota, to determine whether daily users of
      nonsteroidal antiinflammatory drugs (NSAIDs) were at lower risk than nondaily
      NSAID users of developing benign prostatic hyperplasia. Participants completed
      validated questionnaires during a home visit, including information about daily
      NSAID use. A random subset of 634 men also participated in a clinical evaluation
      including transrectal ultrasonography and assessment of serum prostate-specific
      antigen levels. Examinations and questionnaires were repeated biennially through
      2002. Benign prostatic hyperplasia measures included development of
      moderate/severe urinary symptoms (American Urological Association Symptom Index
      score >7), low maximum urinary flow rate (<12 ml/second), prostate volume >30 ml,
      or prostate-specific antigen level >1.4 ng/ml. After adjustment for age, daily
      NSAID use was inversely associated with onset of moderate/severe urinary symptoms
      (hazard ratio (HR) = 0.73, 95% confidence interval (CI): 0.64, 0.82), low maximum
      flow rate (HR = 0.51, 95% CI: 0.43, 0.61), increased prostate volume (HR = 0.53,
      95% CI: 0.41, 0.68), and elevated prostate-specific antigen level (HR = 0.52, 95%
      CI: 0.40, 0.68). In age-specific analyses, inverse associations between NSAID use
      and urinary measures tended to be stronger in the oldest age groups, although
      this interaction was statistically significant for only obstructive symptoms and
      treatment. Results suggest that NSAID use may prevent or delay development of
      benign prostatic hyperplasia.

PMID- 16905645
TI  - Meta-analysis of vitamin D receptor polymorphisms and type 1 diabetes: a HuGE
      review of genetic association studies.
AB  - Several polymorphisms in the vitamin D receptor (VDR) gene have been reported to
      be associated with the risk of developing type 1 diabetes, yet published findings
      have been conflicting. In this study, the authors attempted to evaluate the
      evidence regarding the association. They searched all relevant reports from
      original papers published from 1997 to December 2005. Predefined criteria were
      used to identify 1) case-control association studies examining the FokI (11
      studies), BsmI (13 studies), ApaI (9 studies), and TaqI (7 studies) polymorphisms
      and 2) a few family-transmission studies with analysis of these four
      polymorphisms. In random-effects modeling, the 95% confidence intervals of the
      summary odds ratios for all four polymorphisms included 1, indicating no effect.
      Except for FokI, no heterogeneity was found. The 95% confidence intervals of the
      transmission proportions all included 0.5, indicating no effect. Thus, the
      authors found no evidence for an association between VDR gene polymorphisms and
      type 1 diabetes risk in either case-control studies or family-transmission
      studies. In fact, a reanalysis of previously published data (McDermott et al.,
      Diabetologia 1997;40:971-5) indicated no evidence of an association as reported.

PMID- 16905644
TI  - Falls, sarcopenia, and growth in early life: findings from the Hertfordshire
      cohort study.
AB  - Recent studies have shown that people whose early growth is poor have an
      increased risk of sarcopenia. Sarcopenia is an important risk factor for falls,
      but it is not known whether poor early growth is related to falls. The authors
      investigated this association in the Hertfordshire Cohort Study (1998-2004),
      where 2,148 participants from the United Kingdom provided their history of falls.
      Grip strength was used as a marker of sarcopenia. Birth weight, weight at 1 year,
      and conditional infant growth were analyzed in relation to history of falls. The
      prevalence of any fall in the last year was 14.3% for men and 22.5% for women.
      Falls in the last year were inversely related to adult grip strength, height, and
      walking speed in men and women as well as to lower conditional infant growth in
      men (odds ratio = 1.27, 95% confidence interval: 1.04, 1.56 per standard
      deviation decrease in conditional infant growth; p = 0.02). This association was
      attenuated after adjustment for grip strength. These findings support an
      association between poor early growth and falls in older men that appears to be
      mediated partly through sarcopenia. The lack of a relation with birth weight
      suggests that postnatal rather than prenatal influences on muscle growth and
      development may be important regarding the risk of falls in later life.

PMID- 16905646
TI  - Peripheral insensate neuropathy--a tall problem for US adults?
AB  - The relation between height and lower extremity peripheral insensate neuropathy
      among persons with and without diabetes was examined by use of the 1999-2002 US
      National Health and Nutrition Examination Survey with 5,229 subjects aged 40 or
      more years. A monofilament was used to determine whether any of three areas on
      each foot were insensate. Peripheral insensate neuropathy was defined as the
      presence of one or more insensate areas. Its prevalence was nearly twice as high
      among persons with diabetes (21.2%) as among those without diabetes (11.5%; p <
      0.001). Men (16.2%) had 1.7 times the prevalence of peripheral insensate
      neuropathy as did women (9.4%), but the difference was not significant after
      adjustment for height. Greater height was associated with increased peripheral
      insensate neuropathy prevalence among persons with and without diabetes (p <
      0.001). This association was characterized by a sharp increase in prevalence
      among persons who were taller than 175.5 cm. Peripheral insensate neuropathy risk
      was significantly higher among those taller than 175.5 cm (adjusted odds ratio =
      2.3, 95% confidence interval: 1.5, 3.5). The authors conclude that body height is
      an important correlate of peripheral insensate neuropathy. This association
      largely accounts for the difference in peripheral insensate neuropathy prevalence
      between men and women. Height may help health-care providers to identify persons
      at high risk of peripheral insensate neuropathy.

PMID- 16905647
TI  - The housekeeping dipeptide permease is the Escherichia coli heme transporter and
      functions with two optional peptide binding proteins.
AB  - Heme, a major iron source, is transported through the outer membrane of Gram
      negative bacteria by specific heme/hemoprotein receptors and through the inner
      membrane by heme-specific, periplasmic, binding protein-dependent, ATP-binding
      cassette permeases. Escherichia coli K12 does not use exogenous heme, and no heme
      uptake genes have been identified. Nevertheless, a recombinant E. coli strain
      expressing just one foreign heme outer membrane receptor can use exogenous heme
      as an iron source. This result suggests either that heme might be able to cross
      the cytoplasmic membrane in the absence of specific carrier or that there is a
      functional inner membrane heme transporter. Here, we show that to use heme iron
      E. coli requires the dipeptide inner membrane ATP-binding cassette transporter
      (DppBCDF) and either of two periplasmic binding proteins: MppA, the L-alanyl
      gamma-D-glutamyl-meso-diaminopimelate binding protein, or DppA, the dipeptide
      binding protein. Thus, wild-type E. coli has a peptide/heme permease despite
      being unable to use exogenous heme. DppA, which shares sequence similarity with
      the Haemophilus influenzae heme-binding protein HbpA, and MppA are functional
      heme-binding proteins. Peptides compete with heme for binding both "in vitro" and
      "in vivo."

PMID- 16905648
TI  - Orientation selectivity in visual cortex by fluctuation-controlled criticality.
AB  - Within a large-scale neuronal network model of macaque primary visual cortex, we
      examined how intrinsic dynamic fluctuations in synaptic currents modify the
      effect of strong recurrent excitation on orientation selectivity. Previously, we
      showed that, using a strong network inhibition countered by feedforward and
      recurrent excitation, the cortical model reproduced many observed properties of
      simple and complex cells. However, that network's complex cells were poorly
      selective for orientation, and increasing cortical self-excitation led to network
      instabilities and unrealistically high firing rates. Here, we show that a
      sparsity of connections in the network produces large, intrinsic fluctuations in
      the cortico-cortical conductances that can stabilize the network and that there
      is a critical level of fluctuations (controllable by sparsity) that allows strong
      cortical gain and the emergence of orientation-selective complex cells. The
      resultant sparse network also shows near contrast invariance in its selectivity
      and, in agreement with recent experiments, has extracellular tuning properties
      that are similar in pinwheel center and iso-orientation regions, whereas
      intracellular conductances show positional dependencies. Varying the strength of
      synaptic fluctuations by adjusting the sparsity of network connectivity, we
      identified a transition between the dynamics of bistability and without
      bistability. In a network with strong recurrent excitation, this transition is
      characterized by a near hysteretic behavior and a rapid rise of network firing
      rates as the synaptic drive or stimulus input is increased. We discuss the
      connection between this transition and orientation selectivity in our model of
      primary visual cortex.

PMID- 16905649
TI  - Bistable expression of WOR1, a master regulator of white-opaque switching in
      Candida albicans.
AB  - Candida albicans, a commensal organism and a pathogen of humans, can switch
      stochastically between a white phase and an opaque phase without an intermediate
      phase. The white and opaque phases have distinct cell shapes and gene expression
      programs. Once switched, each phase is stable for many cell divisions. White
      opaque switching is under a1-alpha2 repression and therefore only happens in a or
      alpha cells. Mechanisms that control the switching are unknown. Here, we identify
      Wor1 (white-opaque regulator 1) as a master regulator of white-opaque switching.
      The deletion of WOR1 blocks opaque cell formation. The ectopic expression of WOR1
      converts all cells to stable opaque cells in a or alpha cells. In addition, the
      ectopic expression of WOR1 in a/alpha cells is sufficient to induce opaque cell
      formation. Importantly, WOR1 expression displays an all-or-none pattern. It is
      undetectable in white cells, and it is highly expressed in opaque cells. The
      ectopic expression of Wor1 induces the transcription of WOR1 from the WOR1 locus,
      which correlates with the switch to opaque phase. We present genetic evidence for
      feedback regulation of WOR1 transcription. The feedback regulation explains the
      bistable and stochastic nature of white-opaque switching.

PMID- 16905650
TI  - The peptide-catalyzed stereospecific synthesis of tetroses: a possible model for
      prebiotic molecular evolution.
AB  - Using a water-based prebiotic model of sugar synthesis involving glycolaldehyde
      self-condensation, we demonstrate that homochiral L-dipeptide catalysts lead to
      the stereospecific syntheses of tetroses. The asymmetric effect is largest for
      erythrose, which may reach a D-enantiomeric excess of >80% with L-Val-L-Val
      catalyst. Based on results obtained with various peptides, we propose a possible
      catalytic-reaction intermediate, consisting of an imidazolidinone ring formed
      between the two nitrogen atoms of the peptide catalyst and the C1 of one
      glycolaldehyde molecule. The study was motivated by the premise that exogenous
      material, such as the nonracemic amino acids found in meteorites, could have
      participated in the terrestrial evolution of molecular asymmetry by
      stereospecific catalysis. Because peptides might have formed readily on the early
      Earth, it is possible that their catalytic contribution was relevant in the
      prebiotic processes that preceded the onset of life.

PMID- 16905651
TI  - Systems analysis of PKA-mediated phosphorylation gradients in live cardiac
      myocytes.
AB  - Compartmentation and dynamics of cAMP and PKA signaling are important
      determinants of specificity among cAMP's myriad cellular roles. Both cardiac
      inotropy and the progression of heart disease are affected by spatiotemporal
      variations in cAMP/PKA signaling, yet the dynamic patterns of PKA-mediated
      phosphorylation that influence differential responses to agonists have not been
      characterized. We performed live-cell imaging and systems modeling of PKA
      mediated phosphorylation in neonatal cardiac myocytes in response to G-protein
      coupled receptor stimuli and UV photolysis of "caged" cAMP. cAMP accumulation was
      rate-limiting in PKA-mediated phosphorylation downstream of the beta-adrenergic
      receptor. Prostaglandin E1 stimulated higher PKA activity in the cytosol than at
      the sarcolemma, whereas isoproterenol triggered faster sarcolemmal responses than
      cytosolic, likely due to restricted cAMP diffusion from submembrane compartments.
      Localized UV photolysis of caged cAMP triggered gradients of PKA-mediated
      phosphorylation, enhanced by phosphodiesterase activity and PKA-mediated
      buffering of cAMP. These findings indicate that combining live-cell FRET imaging
      and mechanistic computational models can provide quantitative understanding of
      spatiotemporal signaling.

PMID- 16905652
TI  - The synechocystis sp PCC 6803 oxa1 homolog is essential for membrane integration
      of reaction center precursor protein pD1.
AB  - Synechocystis sp PCC 6803 Slr1471p, an Oxa1p/Alb3/YidC homolog, is an essential
      protein for cell viability for which functions in thylakoid membrane biogenesis
      and cell division have been proposed. Using a fusion of green fluorescent protein
      to the C terminus of Slr1471p, we found that the mutant slr1471-gfp is
      photochemically inhibited when light intensities increase to 80 micromol x m(-2)
      x s(-1). We show that photoinhibition correlates with an increased redox
      potential of the reaction center quinone Q(A)(-) and a decreased redox potential
      of Q(B)(-). Analysis reveals that membrane integration of the D1 precursor
      protein is affected, leading to the accumulation of pD1 in the membrane phase. We
      show that Slr1471p interacts directly with the D1 protein and discuss why the
      accumulation of pD1 in two reaction center assembly intermediates is dependent on
      Slr1471p.

PMID- 16905653
TI  - Multiple avirulence paralogues in cereal powdery mildew fungi may contribute to
      parasite fitness and defeat of plant resistance.
AB  - Powdery mildews, obligate biotrophic fungal parasites on a wide range of
      important crops, can be controlled by plant resistance (R) genes, but these are
      rapidly overcome by parasite mutants evading recognition. It is unknown how this
      rapid evolution occurs without apparent loss of parasite fitness. R proteins
      recognize avirulence (AVR) molecules from parasites in a gene-for-gene manner and
      trigger defense responses. We identify AVR(a10) and AVR(k1) of barley powdery
      mildew fungus, Blumeria graminis f sp hordei (Bgh), and show that they induce
      both cell death and inaccessibility when transiently expressed in Mla10 and Mlk1
      barley (Hordeum vulgare) varieties, respectively. In contrast with other reported
      fungal AVR genes, AVR(a10) and AVR(k1) encode proteins that lack secretion signal
      peptides and enhance infection success on susceptible host plant cells. AVR(a10)
      and AVR(k1) belong to a large family with >30 paralogues in the genome of Bgh,
      and homologous sequences are present in other formae speciales of the fungus
      infecting other grasses. Our findings imply that the mildew fungus has a
      repertoire of AVR genes, which may function as effectors and contribute to
      parasite virulence. Multiple copies of related but distinct AVR effector
      paralogues might enable populations of Bgh to rapidly overcome host R genes while
      maintaining virulence.

PMID- 16905654
TI  - Visualizing plant development and gene expression in three dimensions using
      optical projection tomography.
AB  - A deeper understanding of the mechanisms that underlie plant growth and
      development requires quantitative data on three-dimensional (3D) morphology and
      gene activity at a variety of stages and scales. To address this, we have
      explored the use of optical projection tomography (OPT) as a method for capturing
      3D data from plant specimens. We show that OPT can be conveniently applied to a
      wide variety of plant material at a range of scales, including seedlings, leaves,
      flowers, roots, seeds, embryos, and meristems. At the highest resolution, large
      individual cells can be seen in the context of the surrounding plant structure.
      For naturally semitransparent structures, such as roots, live 3D imaging using
      OPT is also possible. 3D domains of gene expression can be visualized using
      either marker genes, such as beta-glucuronidase, or more directly by whole-mount
      in situ hybridization. We also describe tools and software that allow the 3D data
      to be readily quantified and visualized interactively in different ways.

PMID- 16905655
TI  - Biz1, a zinc finger protein required for plant invasion by Ustilago maydis,
      regulates the levels of a mitotic cyclin.
AB  - Plant invasion by pathogenic fungi involves regulated growth and highly organized
      fungal morphological changes. For instance, when the smut fungus Ustilago maydis
      infects maize (Zea mays), its dikaryotic infective filament is cell cycle
      arrested, and appressoria are differentiated prior to plant penetration. Once the
      filament enters the plant, the cell cycle block is released and fungal cells
      begin proliferation, suggesting a tight interaction between plant invasion and
      the cell cycle and morphogenesis control systems. We describe a novel factor,
      Biz1 (b-dependent zinc finger protein), which has two Cys(2)His(2) zinc finger
      domains and nuclear localization, suggesting a transcriptional regulatory
      function. The deletion of biz1 shows no detectable phenotypic alterations during
      axenic growth. However, mutant cells show a severe reduction in appressoria
      formation and plant penetration, and those hyphae that invade the plant arrest
      their pathogenic development directly after plant penetration. biz1 is induced
      via the b-mating-type locus, the key control instance for pathogenic development.
      The gene is expressed at high levels throughout pathogenic development, which
      induces a G2 cell cycle arrest that is a direct consequence of the downregulation
      of the mitotic cyclin Clb1. Our data support a model in which Biz1 is involved in
      cell cycle arrest preceding plant penetration as well as in the induction of
      appressoria.

PMID- 16905656
TI  - Tobacco WLIM1 is a novel F-actin binding protein involved in actin cytoskeleton
      remodeling.
AB  - We used confocal microscopy and in vitro analyses to show that Nicotiana tabacum
      WLIM1, a LIM domain protein related to animal Cys-rich proteins, is a novel actin
      binding protein in plants. Green fluorescent protein (GFP)-tagged WLIM1 protein
      accumulated in the nucleus and cytoplasm of tobacco BY2 cells. It associated
      predominantly with actin cytoskeleton, as demonstrated by colabeling and
      treatment with actin-depolymerizing latrunculin B. High-speed cosedimentation
      assays revealed the ability of WLIM1 to bind directly to actin filaments with
      high affinity. Fluorescence recovery after photobleaching and fluorescence loss
      in photobleaching showed a highly dynamic in vivo interaction of WLIM1-GFP with
      actin filaments. Expression of WLIM1-GFP in BY2 cells significantly delayed
      depolymerization of the actin cytoskeleton induced by latrunculin B treatment.
      WLIM1 also stabilized actin filaments in vitro. Importantly, expression of WLIM1
      GFP in Nicotiana benthamiana leaves induces significant changes in actin
      cytoskeleton organization, specifically, fewer and thicker actin bundles than in
      control cells, suggesting that WLIM1 functions as an actin bundling protein. This
      hypothesis was confirmed by low-speed cosedimentation assays and direct
      observation of F-actin bundles that formed in vitro in the presence of WLIM1.
      Taken together, these data identify WLIM1 as a novel actin binding protein that
      increases actin cytoskeleton stability by promoting bundling of actin filaments.

PMID- 16905657
TI  - Arabidopsis EPSIN1 plays an important role in vacuolar trafficking of soluble
      cargo proteins in plant cells via interactions with clathrin, AP-1, VTI11, and
      VSR1.
AB  - Epsin and related proteins play important roles in various steps of protein
      trafficking in animal and yeast cells. Many epsin homologs have been identified
      in plant cells from analysis of genome sequences. However, their roles have not
      been elucidated. Here, we investigate the expression, localization, and
      biological role in protein trafficking of an epsin homolog, Arabidopsis thaliana
      EPSIN1, which is expressed in most tissues we examined. In the cell, one pool of
      EPSIN1 is associated with actin filaments, producing a network pattern, and a
      second pool localizes primarily to the Golgi complex with a minor portion to the
      prevacuolar compartment, producing a punctate staining pattern. Protein pull-down
      and coimmunoprecipitation experiments reveal that Arabidopsis EPSIN1 interacts
      with clathrin, VTI11, gamma-adaptin-related protein (gamma-ADR), and vacuolar
      sorting receptor1 (VSR1). In addition, EPSIN1 colocalizes with clathrin and
      VTI11. The epsin1 mutant, which has a T-DNA insertion in EPSIN1, displays a
      defect in the vacuolar trafficking of sporamin:green fluorescent protein (GFP),
      but not in the secretion of invertase:GFP into the medium. Stably expressed
      HA:EPSIN1 complements this trafficking defect. Based on these data, we propose
      that EPSIN1 plays an important role in the vacuolar trafficking of soluble
      proteins at the trans-Golgi network via its interaction with gamma-ADR, VTI11,
      VSR1, and clathrin.

PMID- 16905658
TI  - Interaction between rice MYBGA and the gibberellin response element controls
      tissue-specific sugar sensitivity of alpha-amylase genes.
AB  - Expression of alpha-amylase genes during cereal grain germination and seedling
      growth is regulated negatively by sugar in embryos and positively by gibberellin
      (GA) in endosperm through the sugar response complex (SRC) and the GA response
      complex (GARC), respectively. We analyzed two alpha-amylase promoters, alphaAmy3
      containing only SRC and alphaAmy8 containing overlapped SRC and GARC. alphaAmy3
      was sugar-sensitive but GA-nonresponsive in both rice (Oryza sativa) embryos and
      endosperms, whereas alphaAmy8 was sugar-sensitive in embryos and GA-responsive in
      endosperms. Mutation of the GA response element (GARE) in the alphaAmy8 promoter
      impaired its GA response but enhanced sugar sensitivity, and insertion of GARE in
      the alphaAmy3 promoter rendered it GA-responsive but sugar-insensitive in
      endosperms. Expression of the GARE-interacting transcription factor MYBGA was
      induced by GA in endosperms, correlating with the endosperm-specific alphaAmy8 GA
      response. alphaAmy8 became sugar-sensitive in MYBGA knockout mutant endosperms,
      suggesting that the MYBGA-GARE interaction overrides the sugar sensitivity of
      alphaAmy8. In embryos overexpressing MYBGA, alphaAmy8 became sugar-insensitive,
      indicating that MYBGA affects sugar repression. alpha-Amylase promoters active in
      endosperms contain GARE, whereas those active in embryos may or may not contain
      GARE, confirming that the GARE and GA-induced MYBGA interaction prevents sugar
      feedback repression of endosperm alpha-amylase genes. We demonstrate that the
      MYBGA-GARE interaction affects sugar feedback control in balanced energy
      production during seedling growth and provide insight into the control mechanisms
      of tissue-specific regulation of alpha-amylase expression by sugar and GA
      signaling interference.

PMID- 16905659
TI  - The cytoskeleton maintains organelle partitioning required for single-cell C4
      photosynthesis in Chenopodiaceae species.
AB  - Recently, three Chenopodiaceae species, Bienertia cycloptera, Bienertia
      sinuspersici, and Suaeda aralocaspica, were shown to possess novel C(4)
      photosynthesis mechanisms through the compartmentalization of organelles and
      photosynthetic enzymes into two distinct regions within a single chlorenchyma
      cell. Bienertia has peripheral and central compartments, whereas S. aralocaspica
      has distal and proximal compartments. This compartmentalization achieves the
      equivalent of spatial separation of Kranz anatomy, including dimorphic
      chloroplasts, but within a single cell. To characterize the mechanisms of
      organelle compartmentalization, the distribution of the major organelles relative
      to the cytoskeleton was examined. Examination of the distribution of the
      cytoskeleton using immunofluorescence studies and transient expression of green
      fluorescent protein-tagged cytoskeleton markers revealed a highly organized
      network of actin filaments and microtubules associating with the chloroplasts and
      showed that the two compartments in each cell had different cytoskeletal
      arrangements. Experiments using cytoskeleton-disrupting drugs showed in Bienertia
      and S. aralocaspica that microtubules are critical for the polarized positioning
      of chloroplasts and other organelles. Compartmentalization of the organelles in
      these species represents a unique system in higher plants and illustrates the
      degree of control the plant cell has over the organization and integration of
      multiorganellar processes within its cytoplasm.

PMID- 16905662
TI  - Florigen coming of age after 70 years.

PMID- 16905663
TI  - Dual temporal role of plastid sigma factor 6 in Arabidopsis development.
AB  - Plants contain nuclear-coded sigma factors for initiation of chloroplast
      transcription. The in vivo function of individual members of the sigma gene
      family has become increasingly accessible by knockout and complementation
      strategies. Here we have investigated plastid gene expression in an Arabidopsis
      (Arabidopsis thaliana) mutant with a defective gene for sigma factor 6. RNA gel
      blot hybridization and real-time reverse transcription polymerase chain reaction
      together indicate that this factor has a dual developmental role, with both early
      and persistent (long-term) activities. The early role is evident from the sharp
      decrease of certain plastid transcripts only in young mutant seedlings. The
      second (persistent) role is reflected by the up- and down-regulation of other
      transcripts at the time of primary leaf formation and subsequent vegetative
      development. We conclude that sigma 6 does not represent a general factor, but
      seems to have specialized roles in developmental stage- and gene-specific plastid
      transcription. The possibility that plastid DNA copy number might be responsible
      for the altered transcript patterns in mutant versus wild type was excluded by
      the results of DNA gel-blot hybridization. Retransformation of the knockout line
      with the full-length sigma 6 cDNA further established a causal relationship
      between the functional sigma gene and the resulting phenotype.

PMID- 16905664
TI  - Quantification of plasmodesmatal endoplasmic reticulum coupling between sieve
      elements and companion cells using fluorescence redistribution after
      photobleaching.
AB  - Transgenic tobacco (Nicotiana tabacum) was studied to localize the activity of
      phloem loading during development and to establish whether the endoplasmic
      reticulum (ER) of the companion cell (CC) and the sieve element (SE) reticulum is
      continuous by using a SUC2 promoter-green fluorescent protein (GFP) construct
      targeted to the CC-ER. Expression of GFP marked the collection phloem in source
      leaves and cotyledons as expected, but also the transport phloem in stems,
      petioles, midveins of sink leaves, nonphotosynthetic flower parts, roots, and
      newly germinated seedlings, suggesting that sucrose retrieval along the pathway
      is an integral component of phloem function. GFP fluorescence was limited to CCs
      where it was visualized as a well-developed ER network in close proximity to the
      plasma membrane. ER coupling between CC and SEs was tested in wild-type tobacco
      using an ER-specific fluorochrome and fluorescence redistribution after
      photobleaching (FRAP), and showed that the ER is continuous via pore-plasmodesma
      units. ER coupling between CC and SE was quantified by determining the mobile
      fraction and half-life of fluorescence redistribution and compared with that of
      other cell types. In all tissues, fluorescence recovered slowly when it was rate
      limited by plasmodesmata, contrasting with fast intracellular FRAP. FRAP was
      unaffected by treatment with cytochalasin D. The highest degree of ER coupling
      was measured between CC and SE. Intimate ER coupling is consistent with a
      possible role for ER in membrane protein and signal exchange between CC and SE.
      However, a complete lack of GFP transfer between CC and SE indicated that the
      intraluminal pore-plasmodesma contact has a size exclusion limit below 27 kD.

PMID- 16905665
TI  - Whole-plant growth stage ontology for angiosperms and its application in plant
      biology.
AB  - Plant growth stages are identified as distinct morphological landmarks in a
      continuous developmental process. The terms describing these developmental stages
      record the morphological appearance of the plant at a specific point in its life
      cycle. The widely differing morphology of plant species consequently gave rise to
      heterogeneous vocabularies describing growth and development. Each species or
      family specific community developed distinct terminologies for describing whole
      plant growth stages. This semantic heterogeneity made it impossible to use growth
      stage description contained within plant biology databases to make meaningful
      computational comparisons. The Plant Ontology Consortium
      (http://www.plantontology.org) was founded to develop standard ontologies
      describing plant anatomical as well as growth and developmental stages that can
      be used for annotation of gene expression patterns and phenotypes of all
      flowering plants. In this article, we describe the development of a generic whole
      plant growth stage ontology that describes the spatiotemporal stages of plant
      growth as a set of landmark events that progress from germination to senescence.
      This ontology represents a synthesis and integration of terms and concepts from a
      variety of species-specific vocabularies previously used for describing
      phenotypes and genomic information. It provides a common platform for annotating
      gene function and gene expression in relation to the developmental trajectory of
      a plant described at the organismal level. As proof of concept the Plant Ontology
      Consortium used the plant ontology growth stage ontology to annotate genes and
      phenotypes in plants with initial emphasis on those represented in The
      Arabidopsis Information Resource, Gramene database, and MaizeGDB.

PMID- 16905666
TI  - Effects of zinc deficiency on rice growth and genetic factors contributing to
      tolerance.
AB  - Zinc (Zn) deficiency is the most widespread micronutrient disorder in rice (Oryza
      sativa), but efforts to develop cultivars with improved tolerance have been
      hampered by insufficient understanding of genetic factors contributing to
      tolerance. The objective of this paper was to examine alternative evaluation
      methods and to identify the most informative traits that would provide realistic
      information for rice breeders and to map quantitative trait loci (QTLs)
      associated with tolerance. Screening experiments in low-Zn nutrient solution and
      in a Zn-deficient field did not produce similar tolerance rankings in a set of
      segregating lines, which suggested that rhizosphere effects were of greater
      importance for lowland rice than internal Zn efficiency. The most severe symptom
      in the field was high plant mortality. The occurrence of leaf bronzing, usually
      regarded as indicative of susceptibility, did not necessarily concur with high
      plant mortality, which implied that both were under independent genetic control.
      The QTL mapping experiment conducted in the field with a population derived from
      a cross of IR74 (intolerant) with Jalmagna (tolerant) largely confirmed this.
      Four QTLs associated with plant mortality were detected, and only one of those
      colocalized with one of the four QTLs detected for leaf bronzing. The two most
      influential QTLs for plant mortality were detected on chromosomes 2 and 12. They
      explained 16.6% and 24.2% of the variation, and alleles of the tolerant donor
      parent Jalmagna reduced mortality by 16.6% and 14.8%, respectively. QTLs for
      plant mortality acted in a purely additive manner, whereas digenic epistatic
      interactions were important for leaf bronzing.

PMID- 16905667
TI  - A transgenic approach to understanding the influence of carbonic anhydrase on
      C18OO discrimination during C4 photosynthesis.
AB  - The oxygen isotope composition of atmospheric CO(2) is an important signal that
      helps distinguish between ecosystem photosynthetic and respiratory processes. In
      C(4) plants the carbonic anhydrase (CA)-catalyzed interconversion of CO(2) and
      bicarbonate (HCO(3)(-)) is an essential first reaction for C(4) photosynthesis
      but also plays an important role in the CO(2)-H(2)O exchange of oxygen as it
      enhances the rate of isotopic equilibrium between CO(2) and water. The C(4) dicot
      Flaveria bidentis containing genetically reduced levels of leaf CA (CA(leaf)) has
      been used to test whether changing leaf CA activity influences online
      measurements of C(18)OO discrimination (Delta(18)O) and the proportion of CO(2)
      in isotopic equilibrium with leaf water at the site of oxygen exchange (theta).
      The Delta(18)O in wild-type F. bidentis, which contains high levels of CA
      relative to the rates of net CO(2) assimilation, was less than predicted by
      models of Delta(18)O. Additionally, Delta(18)O was sensitive to small decreases
      in CA(leaf). However, reduced CA activity in F. bidentis had little effect on net
      CO(2) assimilation, transpiration rates (E), and stomatal conductance (g(s))
      until CA levels were less than 20% of wild type. The values of theta determined
      from measurements of Delta(18)O and the (18)O isotopic composition of leaf water
      at the site of evaporation (delta(e)) were low in the wild-type F. bidentis and
      decreased in transgenic plants with reduced levels of CA activity. Measured
      values of theta were always significantly lower than the values of theta
      predicted from in vitro CA activity and gas exchange. The data presented here
      indicates that CA content in a C(4) leaf may not represent the CA activity
      associated with the CO(2)-H(2)O oxygen exchange and therefore may not be a good
      predictor of theta during C(4) photosynthesis. Furthermore, uncertainties in the
      isotopic composition of water at the site of exchange may also limit the ability
      to accurately predict theta in C(4) plants.

PMID- 16905668
TI  - Arabidopsis carboxyl-terminal domain phosphatase-like isoforms share common
      catalytic and interaction domains but have distinct in planta functions.
AB  - An Arabidopsis (Arabidopsis thaliana) multigene family (predicted to be more than
      20 members) encodes plant C-terminal domain (CTD) phosphatases that
      dephosphorylate Ser residues in tandem heptad repeat sequences of the RNA
      polymerase II C terminus. CTD phosphatase-like (CPL) isoforms 1 and 3 are
      regulators of osmotic stress and abscisic acid (ABA) signaling. Evidence
      presented herein indicates that CPL3 and CPL4 are homologs of a prototype CTD
      phosphatase, FCP1 (TFIIF-interacting CTD-phosphatase). CPL3 and CPL4 contain
      catalytic FCP1 homology and breast cancer 1 C terminus (BRCT) domains.
      Recombinant CPL3 and CPL4 interact with AtRAP74, an Arabidopsis ortholog of a
      FCP1-interacting TFIIF subunit. A CPL3 or CPL4 C-terminal fragment that contains
      the BRCT domain mediates molecular interaction with AtRAP74. Consistent with
      their predicted roles in transcriptional regulation, green fluorescent protein
      fusion proteins of CPL3, CPL4, and RAP74 all localize to the nucleus. cpl3
      mutations that eliminate the BRCT or FCP1 homology domain cause ABA
      hyperactivation of the stress-inducible RD29a promoter, whereas RNAi suppression
      of CPL4 results in dwarfism and reduced seedling growth. These results indicate
      CPL3 and CPL4 are a paralogous pair of general transcription regulators with
      similar biochemical properties, but are required for the distinct developmental
      and environmental responses. CPL4 is necessary for normal plant growth and thus
      most orthologous to fungal and metazoan FCP1, whereas CPL3 is an isoform that
      specifically facilitates ABA signaling.

PMID- 16905669
TI  - Transcriptional regulation of gibberellin metabolism genes by auxin signaling in
      Arabidopsis.
AB  - Auxin and gibberellins (GAs) overlap in the regulation of multiple aspects of
      plant development, such as root growth and organ expansion. This coincidence
      raises questions about whether these two hormones interact to regulate common
      targets and what type of interaction occurs in each case. Auxins induce GA
      biosynthesis in a range of plant species. We have undertaken a detailed analysis
      of the auxin regulation of expression of Arabidopsis (Arabidopsis thaliana) genes
      encoding GA 20-oxidases and GA 3-oxidases involved in GA biosynthesis, and GA 2
      oxidases involved in GA inactivation. Our results show that auxin differentially
      up-regulates the expression of various genes involved in GA metabolism, in
      particular several AtGA20ox and AtGA2ox genes. Up-regulation occurred very
      quickly after auxin application; the response was mimicked by incubations with
      the protein synthesis inhibitor cycloheximide and was blocked by treatments with
      the proteasome inhibitor MG132. The effects of auxin treatment reflect endogenous
      regulation because equivalent changes in gene expression were observed in the
      auxin overproducer mutant yucca. The results suggest direct regulation of the
      expression of GA metabolism genes by Aux/IAA and ARF proteins. The physiological
      relevance of this regulation is supported by the observation that the phenotype
      of certain gain-of-function Aux/IAA alleles could be alleviated by GA
      application, which suggests that changes in GA metabolism mediate part of auxin
      action during development.

PMID- 16905670
TI  - Down-regulation of the 26S proteasome subunit RPN9 inhibits viral systemic
      transport and alters plant vascular development.
AB  - Plant viruses utilize the vascular system for systemic movement. The plant
      vascular network also transports water, photosynthates, and signaling molecules
      and is essential for plant growth. However, the molecular mechanisms governing
      vascular development and patterning are still largely unknown. From viral
      transport suppressor screening using virus-induced gene silencing, we identified
      a 26S proteasome subunit, RPN9, which is required for broad-spectrum viral
      systemic transport. Silencing of RPN9 in Nicotiana benthamiana inhibits systemic
      spread of two taxonomically distinct viruses, Tobacco mosaic virus and Turnip
      mosaic virus. The 26S proteasome is a highly conserved eukaryotic protease
      complex controlling many fundamental biochemical processes, but the functions of
      many 26S proteasome regulatory subunits, especially in plants, are still poorly
      understood. We demonstrate that the inhibition of viral systemic transport after
      RPN9 silencing is largely due to alterations in the vascular tissue. RPN9
      silenced plants display extra leaf vein formation with increased xylem and
      decreased phloem. We further illustrate that RPN9 functions at least in part
      through regulation of auxin transport and brassinosteroid signaling, two
      processes that are crucial for vascular formation. We propose that RPN9 regulates
      vascular formation by targeting a subset of regulatory proteins for degradation.
      The brassinosteroid-signaling protein BZR1 is one of the targets.

PMID- 16905671
TI  - Clarification of pathway-specific inhibition by Fourier transform ion cyclotron
      resonance/mass spectrometry-based metabolic phenotyping studies.
AB  - We have developed a metabolic profiling scheme based on direct-infusion Fourier
      transform ion cyclotron resonance mass spectrometry (FT-ICR/MS). The scheme
      consists of: (1) reproducible data collection under optimized FT-ICR/MS
      analytical conditions; (2) automatic mass-error correction and multivariate
      analyses for metabolome characterization using a newly developed metabolomics
      tool (DMASS software); (3) identification of marker metabolite candidates by
      searching a species-metabolite relationship database, KNApSAcK; and (4)
      structural analyses by an MS/MS method. The scheme was applied to metabolic
      phenotyping of Arabidopsis (Arabidopsis thaliana) seedlings treated with
      different herbicidal chemical classes for pathway-specific inhibitions.
      Arabidopsis extracts were directly infused into an electrospray ionization source
      on an FT-ICR/MS system. Acquired metabolomics data were comprised of mass-to
      charge ratio values with ion intensity information subjected to principal
      component analysis, and metabolic phenotypes from the herbicide treatments were
      clearly differentiated from those of the herbicide-free treatment. From each
      herbicide treatment, candidate metabolites representing such metabolic phenotypes
      were found through the KNApSAcK database search. The database search and MS/MS
      analyses suggested dose-dependent accumulation patterns of specific metabolites
      including several flavonoid glycosides. The metabolic phenotyping scheme on the
      basis of FT-ICR/MS coupled with the DMASS program is discussed as a general tool
      for high throughput metabolic phenotyping studies.

PMID- 16905672
TI  - Association of genetic markers within the KIT and KITLG genes with human male
      infertility.
AB  - BACKGROUND: There is much evidence involving the KIT tyrosine kinase receptor and
      its ligand KITLG in the survival and proliferation of germ cells. Animal models
      and functional studies in humans suggest that this signalling pathway plays a
      role in male infertility. METHODS: We studied three and two single-nucleotide
      polymorphisms (SNPs) (rs3819392, rs3134885, rs2237012, rs10506957 and rs995030)
      located within the genomic region of the KIT and KITLG genes, respectively. A
      total of 167 idiopathic infertile men (sperm counts <5 million spz/ml) and 465
      unrelated healthy controls from the same geographical region were genotyped for
      these SNPs. RESULTS: We found a statistically significant association of the
      rs3819392 polymorphism, which is located within the KIT gene, with idiopathic
      male infertility. In addition, a deviation from the Hardy-Weinberg equilibrium
      (HWE) law was observed for rs10506957 polymorphism within the KITLG gene only in
      the infertile group. CONCLUSIONS: Our data indicate that the KIT/KITLG system may
      be involved in a low sperm count trait in humans.

PMID- 16905673
TI  - Understanding and preventing noncontact anterior cruciate ligament injuries: a
      review of the Hunt Valley II meeting, January 2005.
AB  - The incidence of noncontact anterior cruciate ligament injuries in young to
      middle-aged athletes remains high. Despite early diagnosis and appropriate
      operative and nonoperative treatments, posttraumatic degenerative arthritis may
      develop. In a meeting in Atlanta, Georgia (January 2005), sponsored by the
      American Orthopaedic Society for Sports Medicine, a group of physicians, physical
      therapists, athletic trainers, biomechanists, epidemiologists, and other
      scientists interested in this area of research met to review current knowledge on
      risk factors associated with noncontact anterior cruciate ligament injuries,
      anterior cruciate ligament injury biomechanics, and existing anterior cruciate
      ligament prevention programs. This article reports on the presentations,
      discussions, and recommendations of this group.

PMID- 16905674
TI  - Partner violence against women with disabilities: prevalence, risk, and
      explanations.
AB  - Using a representative sample of 7,027 Canadian women living in a marital or
      common-law union, this investigation examined the risk for partner violence
      against women with disabilities relative to women without disabilities. Women
      with disabilities had 40% greater odds of violence in the 5 years preceding the
      interview, and these women appeared to be at particular risk for severe violence.
      An explanatory framework was tested that organized variables based on
      relationship factors, victim-related characteristics, and perpetrator-related
      characteristics. Results showed that perpetrator-related characteristics alone
      accounted for the elevated risk of partner violence against women with
      disabilities. Stakeholders must recognize the problem of partner violence against
      women with disabilities, and efforts to address patriarchal domination and male
      sexual proprietariness appear crucial to reducing their risk of partner violence.

PMID- 16905675
TI  - Physical and sexual assault of women with disabilities.
AB  - North Carolina women were surveyed to examine whether women's disability status
      was associated with their risk of being assaulted within the past year. Women's
      violence experiences were classified into three groups: no violence, physical
      assault only (without sexual assault), and sexual assault (with or without
      physical assault). Multivariable analysis revealed that women with disabilities
      were not significantly more likely than women without disabilities to have
      experienced physical assault alone within the past year (odds ratio [OR] = 1.18,
      95% Confidence Interval [CI] = 0.62 to 2.27); however, women with disabilities
      had more than 4 times the odds of experiencing sexual assault in the past year
      compared to women without disabilities (OR = 4.89, 95% CI = 2.21 to 10.83).

PMID- 16905676
TI  - Disability, psychosocial, and demographic characteristics of abused women with
      physical disabilities.
AB  - In a sample of 415 predominantly minority women with physical disabilities
      recruited from private and public specialty outpatient clinics, we examined
      experiences of physical, sexual, and disability-related abuse within the past
      year and its associations with demographic, disability, and psychosocial
      characteristics. Logistic regression analyses identified 27% of the variance and
      indicated that women with disabilities who were younger, more educated, less
      mobile, more socially isolated, and who had higher levels of depression may have
      a higher likelihood of having experienced abuse in the past year. This model
      correctly identified 84% of the abused women with disabilities. Questions of
      directionality, the role of disability, and validity testing are discussed.

PMID- 16905677
TI  - Older women's descriptions and understandings of their abusers.
AB  - Thirty-eight women who were in abusive relationships since age 55 years were
      interviewed to understand their abuse stories, ways of coping, and health care
      experiences. In responding to these questions, women described the nature of the
      abuse perpetrated by their elderly partners and tried to "make sense" of what
      they had experienced and to define "who" these men were. This took various forms,
      from personal theories about aging, to labels (ethnic stereotyping, demonizing,
      pathologizing) to characterizations of the abuser's private versus public
      behaviors. The authors explore the implications these findings have for assisting
      the elderly victim and perpetrator.

PMID- 16905678
TI  - The impact of differential patterns of physical violence and stalking on mental
      health and help-seeking among women with protective orders.
AB  - This study examined the severity of partner violence on women's mental health and
      help-seeking as well as perceptions of safety and protective-order effectiveness.
      Three groups based on partner violence victimization in the past year were
      compared: (a) women who reported experiencing moderate physical violence but no
      history of severe violence or stalking (n = 102), (b) women who experienced
      severe violence but no history of stalking (n = 142), and (c) women who
      experienced severe violence and stalking (n = 145). Results suggest that stalking
      has a unique impact on victims' mental health and perceived safety, and that
      protections afforded by protective orders may not be adequate for women
      experiencing stalking.

PMID- 16905679
TI  - Correlation between clinical severity in patients with Rett syndrome with a
      p.R168X or p.T158M MECP2 mutation, and the direction and degree of skewing of X
      chromosome inactivation.
AB  - INTRODUCTION: Rett syndrome (RTT) is an X-linked dominant neurodevelopmental
      disorder that is usually associated with mutations in the MECP2 gene. The most
      common mutations in the gene are p.R168X and p.T158M. The influence of X
      chromosome inactivation (XCI) on clinical severity in patients with RTT with
      these mutations was investigated, taking into account the extent and direction of
      skewing. METHODS: Female patients and their parents were recruited from the UK
      and Australia. Clinical severity was measured by the Pineda Severity and Kerr
      profile scores. The degree of XCI and its direction relative to the X chromosome
      parent of origin were measured in DNA prepared from peripheral blood leucocytes,
      and allele-specific polymerase chain reaction was used to determine the parental
      origin of mutation. Combining these, the percentage of cells expected to express
      the mutant allele was calculated. RESULTS: Linear regression analysis was
      undertaken for fully informative cases with p.R168X (n = 23) and p.T158M (n = 20)
      mutations. A statistically significant increase in clinical severity with
      increase in the proportion of active mutated allele was shown for both the
      p.R168X and p.T158M mutations. CONCLUSIONS: XCI may vary in neurological and
      haematological tissues. However, these data are the first to show a relationship
      between the degree and direction of XCI in leucocytes and clinical severity in
      RTT, although the clinical utility of this in giving a prognosis for individual
      patients is unclear.

PMID- 16905681
TI  - Transcript levels of the intermediate size or grey zone fragile X mental
      retardation 1 alleles are raised, and correlate with the number of CGG repeats.
AB  - BACKGROUND: Grey zone or intermediate alleles are one of the three recognised
      classes of the X-linked fragile X mental retardation 1 (FMR1) gene showing
      intergenerational instability. These classes are defined according to the number
      of CGG repeats in the FMR1 5'-untranslated region. Although large CGG expansions
      (>200 repeats) cause a neurodevelopmental anomaly through silencing of the gene,
      resulting in a deficit of FMR1 specific protein, smaller expansions
      (approximately 55-200 repeats) are associated with an increased transcription and
      late-onset specific phenotypes. Those alleles with a CGG repeat number ranging
      between approximately 41 and 55 are relatively poorly defined with regard to both
      transcriptional and translational activity, and also potential phenotypic
      effects. METHODS AND RESULTS: Based on a sample of 33 males carrying FMR1 alleles
      within the grey zone range, defined here as 41-60 CGGs, we show an increased
      transcriptional activity relative to that seen in common alleles (5-40 CGGS).
      This is the first study to report a significant relationship between FMR1 mRNA
      levels and CGG repeat number within the grey zone range (p<0.001). From a
      piecewise linear regression model, the threshold for onset of the increase in
      mRNA levels as a function of CGG repeat size has been determined at approximately
      39 repeats (standard error (SE) 3.24), and that for the reduction in the rate of
      this increase at approximately 54 repeats (SE 4.27). CONCLUSIONS: The ambiguities
      associated with the definition and transcription dynamics of the FMR1 gene within
      the grey zone range are dealt with. There may be specific phenotypes associated
      with the toxic "gain-of-function" effect of raised mRNA.

PMID- 16905680
TI  - Evaluation of BRCA1 and BRCA2 mutation prevalence, risk prediction models and a
      multistep testing approach in French-Canadian families with high risk of breast
      and ovarian cancer.
AB  - BACKGROUND AND OBJECTIVE: In clinical settings with fixed resources allocated to
      predictive genetic testing for high-risk cancer predisposition genes, optimal
      strategies for mutation screening programmes are critically important. These
      depend on the mutation spectrum found in the population under consideration and
      the frequency of mutations detected as a function of the personal and family
      history of cancer, which are both affected by the presence of founder mutations
      and demographic characteristics of the underlying population. The results of
      multistep genetic testing for mutations in BRCA1 or BRCA2 in a large series of
      families with breast cancer in the French-Canadian population of Quebec, Canada
      are reported. METHODS: A total of 256 high-risk families were ascertained from
      regional familial cancer clinics throughout the province of Quebec. Initially,
      families were tested for a panel of specific mutations known to occur in this
      population. Families in which no mutation was identified were then
      comprehensively tested. Three algorithms to predict the presence of mutations
      were evaluated, including the prevalence tables provided by Myriad Genetics
      Laboratories, the Manchester Scoring System and a logistic regression approach
      based on the data from this study. RESULTS: 8 of the 15 distinct mutations found
      in 62 BRCA1/BRCA2-positive families had never been previously reported in this
      population, whereas 82% carried 1 of the 4 mutations currently observed in > or
      =2 families. In the subset of 191 families in which at least 1 affected
      individual was tested, 29% carried a mutation. Of these 27 BRCA1-positive and 29
      BRCA2-positive families, 48 (86%) were found to harbour a mutation detected by
      the initial test. Among the remaining 143 inconclusive families, all 8 families
      found to have a mutation after complete sequencing had Manchester Scores > or
      =18. The logistic regression and Manchester Scores provided equal predictive
      power, and both were significantly better than the Myriad Genetics Laboratories
      prevalence tables (p<0.001). A threshold of Manchester Score > or =18 provided an
      overall sensitivity of 86% and a specificity of 82%, with a positive predictive
      value of 66% in this population. CONCLUSION: In this population, a testing
      strategy with an initial test using a panel of reported recurrent mutations,
      followed by full sequencing in families with Manchester Scores > or =18,
      represents an efficient test in terms of overall cost and sensitivity.

PMID- 16905683
TI  - The role of genetic variants of matrix metalloproteinases in coronary and carotid
      atherosclerosis.
AB  - Current evidence suggests that matrix metalloproteinases (MMPs) have a role in
      early atherosclerosis, plaque rupture and myocardial infarction. Polymorphisms in
      MMP genes have been examined for associations with atherosclerosis, but
      interpretation is complicated by methodological issues. This article presents a
      systematic review of these association studies and a meta-analysis of available
      data for polymorphisms where a sufficient number of studies was available. The 5A
      allele of the MMP3 5A/6A polymorphism was associated with acute myocardial
      infarction (odds ratio (OR) 1.26, 95% confidence interval (CI) 1.1 to 1.4,
      p<0.001), suggesting its role in plaque rupture. There was no association with
      the functional MMP9 -1562C/T polymorphism (OR 1.11, 95% CI 1.0 to 1.3, p = 0.18).
      Current data provide evidence for the role of MMP3 polymorphism in plaque
      destabilisation, but elucidation of the role of other MMP gene variants in
      atherosclerosis will depend on better study design, including a larger sample
      size, extensive screening of individual genes with haplotype analysis and
      replication of studies to avoid publication bias.

PMID- 16905682
TI  - Features associated with germline CDKN2A mutations: a GenoMEL study of melanoma
      prone families from three continents.
AB  - BACKGROUND: The major factors individually reported to be associated with an
      increased frequency of CDKN2A mutations are increased number of patients with
      melanoma in a family, early age at melanoma diagnosis, and family members with
      multiple primary melanomas (MPM) or pancreatic cancer. METHODS: These four
      features were examined in 385 families with > or =3 patients with melanoma pooled
      by 17 GenoMEL groups, and these attributes were compared across continents.
      RESULTS: Overall, 39% of families had CDKN2A mutations ranging from 20% (32/162)
      in Australia to 45% (29/65) in North America to 57% (89/157) in Europe. All four
      features in each group, except pancreatic cancer in Australia (p = 0.38),
      individually showed significant associations with CDKN2A mutations, but the
      effects varied widely across continents. Multivariate examination also showed
      different predictors of mutation risk across continents. In Australian families,
      > or =2 patients with MPM, median age at melanoma diagnosis < or =40 years and >
      or =6 patients with melanoma in a family jointly predicted the mutation risk. In
      European families, all four factors concurrently predicted the risk, but with
      less stringent criteria than in Australia. In North American families, only > or
      =1 patient with MPM and age at diagnosis < or =40 years simultaneously predicted
      the mutation risk. CONCLUSIONS: The variation in CDKN2A mutations for the four
      features across continents is consistent with the lower melanoma incidence rates
      in Europe and higher rates of sporadic melanoma in Australia. The lack of a
      pancreatic cancer-CDKN2A mutation relationship in Australia probably reflects the
      divergent spectrum of mutations in families from Australia versus those from
      North America and Europe. GenoMEL is exploring candidate host, genetic and/or
      environmental risk factors to better understand the variation observed.

PMID- 16905684
TI  - Quetiapine treatment of psychosis associated with dementia: a double-blind,
      randomized, placebo-controlled clinical trial.
AB  - OBJECTIVES: The objectives of this study were to evaluate the efficacy, safety,
      and tolerability of quetiapine for treating psychosis in patients with
      probable/possible Alzheimer disease and assess its impact on other
      psychopathology and social and daily functioning. METHOD: The authors conducted a
      multicenter, double-blind, placebo-controlled, randomized trial of flexibly dosed
      quetiapine and haloperidol. Primary outcomes were change in total Brief
      Psychiatric Rating Scale (BPRS) and Clinical Global Impressions-Severity of
      Illness (CGI-S) scores at week 10. Secondary outcomes included BPRS factors,
      Neuropsychiatric Inventory (NPI), Multidimensional Observation Scale for Elderly
      Subjects (MOSES), and Physical Self-Maintenance Scale (PSMS). RESULTS: Two
      hundred eighty-four participants (mean age: 83.2 years) were randomized; 63.4%
      completed; and mean Mini-Mental State Examination score was 12.8. Median of the
      mean daily dose was 96.9 mg for quetiapine and 1.9 mg for haloperidol. No
      differential benefit was seen on any psychosis measure. BPRS agitation factor
      scores improved with quetiapine versus placebo and not quetiapine versus
      haloperidol. BPRS anergia scores worsened with haloperidol versus quetiapine but
      not quetiapine versus placebo. No NPI factors showed change, including the
      agitation factor. MOSES Withdrawal Subscale and PSMS total scores worsened with
      haloperidol versus quetiapine. Somnolence occurred in 25.3%, 36.2%, and 4.1% of
      the quetiapine, haloperidol, and placebo groups, respectively; parkinsonism was
      most prevalent in the haloperidol group; other safety and tolerability measures
      differed little among groups. CONCLUSION: All treatment groups showed improvement
      in measures of psychosis without significant differences between them when
      planned comparisons were performed. Participants treated with quetiapine or
      haloperidol showed inconsistent evidence of improvement in agitation.
      Tolerability was better with quetiapine compared with haloperidol.

PMID- 16905686
TI  - Melatonin treatment reverts age-related changes in Guinea pig gallbladder
      neuromuscular transmission and contractility.
AB  - The incidence of gallbladder illness increases with age, but the altered
      mechanisms leading to gallbladder dysfunction are poorly understood. Here we
      determine the age-related alterations in gallbladder contractility and the impact
      of melatonin treatment. Isometric tension changes in response to electrical field
      stimulation and to agonists were recorded from guinea pig gallbladder muscle
      strips. [Ca(2+)](i) was determined by epifluorescence microscopy in fura-2 loaded
      isolated gallbladder smooth muscle cells, and F-actin content was quantified by
      confocal microscopy. Aging reduced neurogenic contractions, which was associated
      with the impairment of nitrergic innervation and with increased responsiveness of
      capsaicin-sensitive relaxant nerves, possibly involving calcitonin gene-related
      peptide. Melatonin treatment for 4 weeks restored neurogenic responses to normal
      values, with an associated recovery of nitrergic function and the disappearance
      of the capsaicin-sensitive component. Aging also reduced the contractile
      responses to cholecystokinin and Ca(2+) influx. The impaired contractility only
      correlated with diminished Ca(2+) mobilization in response to activation of
      Ca(2+) influx. Melatonin improved contractility and increased smooth muscle F
      actin content without changing Ca(2+) homeostasis. In conclusion, aging impairs
      gallbladder function as the result of changes in the inhibitory neuromodulation
      of smooth muscle contractility and the reduction in the myogenic response to
      contractile agonists. Impaired contractility seems to be related to decreased
      Ca(2+) influx and damage of contractile proteins. Melatonin significantly
      ameliorated these age-related changes.

PMID- 16905685
TI  - Genome survey for loci that influence successful aging: results at 10-cM
      resolution.
AB  - OBJECTIVE: A systematic genome survey was initiated to identify loci that affect
      the likelihood of reaching age 90 with preserved cognition (successful aging).
      METHODS: The genome survey was conducted at 10-cM resolution for simple sequence
      tandem repeat polymorphisms (SSTRPs) that identify genes for Successful AGing
      (SAG loci) by virtue of linkage disequilibrium. Efficiency was enhanced by
      genotyping pools of DNA from 100 cognitively intact elders and 100 young (18-25
      years) adults. The comparison groups included equal numbers of white men and
      women of similar ethnicity that were recruited from the southwestern Pennsylvania
      region. RESULTS: Our genome survey identified nine SAG candidate loci that may
      influence the likelihood of reaching age 90 or more with preserved cognition. Two
      of the autosomal SAG loci revealed stronger allelic associations with successful
      aging in men than women (D1S1728, D8S264) and two were located on sex chromosomes
      (DXS9902, DYS390). DXS9902 resides within a predicted gene, whereas six of the
      SAG loci are located within regions previously reported to show linkage to other
      phenotypes. CONCLUSIONS: The results of our study suggest that loci with
      differential effects on the successful aging of men and women may be common. The
      majority of the SAG candidate loci detected in this study overlap with regions
      previously reported to show linkage to susceptibility genes for cardiovascular
      disorders, psychiatric disorders, and the accumulation of tissue damage resulting
      from oxidative stress.

PMID- 16905687
TI  - Effects of prenatal ethanol exposure on the excitability of ventral tegmental
      area dopamine neurons in vitro.
AB  - Prenatal ethanol exposure leads to a persistent reduction in the number of
      spontaneously active dopaminergic (DA) neurons (DA neuron population activity) in
      the ventral tegmental area (VTA) in developing and adult animals. This effect
      might contribute to the dysfunction of the mesolimbic/cortical DA system and
      attention problems in children with fetal alcohol spectrum disorders. To
      characterize the underlying cellular mechanism for prenatal ethanol exposure
      induced reduction in VTA DA neuron population activity, we used the whole-cell
      patch-clamp technique to study the membrane properties of putative VTA DA neurons
      in brain slices in 2- to 3-week-old control and prenatal ethanol-exposed animals.
      The results show that prenatal ethanol exposure did not impair the spontaneous
      pacemaker activity in putative VTA DA neurons but reduced the frequency of evoked
      action potentials. In addition, prenatal ethanol exposure led to a reduction in
      hyperpolarization-induced cation current (I(h)) and an up-regulation of
      somatodendritic DA autoreceptors. The above prenatal ethanol exposure-induced
      changes could decrease the excitability of VTA DA neurons. However, they do not
      seem to play a role in reduced VTA DA neuron population activity in vivo, an
      effect thought to be mediated by excessive excitation leading to depolarization
      inactivation. Taken together, the above results indicate that prenatal ethanol
      exposure-induced reduction in VTA DA neuron population activity in vivo is not
      caused by changes in the intrinsic pacemaker activity or other membrane
      properties and could instead be caused by altered inputs to VTA DA neurons.

PMID- 16905688
TI  - Elucidating the effect of final-day dosing of rifampin in induction studies on
      hepatic drug disposition and metabolism.
AB  - Because rifampin (RIF) induces hepatic enzymes and inhibits uptake transporters,
      dosing a drug that is a dual substrate of enzymes and uptake transporters on the
      final day of an inducing regimen should exhibit less inductive effect than dosing
      on the following day in the absence of RIF, since RIF decreases drug uptake into
      liver. In vitro and in vivo rat studies were conducted using digoxin as a model
      substrate. Digoxin was administered to an uninduced control group to obtain
      baseline values. The second group (induced with dexamethasone) received digoxin
      alone, mimicking administration of a test drug 1 day following completion of an
      induction regimen, whereas the third group (induced) received digoxin with RIF
      mimicking the concomitant dosing on the final day of an induction regimen.
      Results from hepatocyte concentration-time course studies showed that compared
      with uninduced control (26.9 +/- 1.3 microM . min/mg), digoxin area under the
      time-concentration curve (AUC) in induced cells when no RIF is present decreased
      significantly (13.7 +/- 0.9 microM . min/mg; p < 0.01), suggesting induction of
      Cyp3a. However, digoxin AUC for induced cells in the presence of RIF (27.3 +/-
      0.9 microM . min/mg) matched the control. Rat pharmacokinetic studies showed that
      compared with digoxin clearance in uninduced controls (7.08 +/- 1.57 ml/min/kg),
      digoxin clearance in induced rats increased 2-fold (15.6 +/- 3.7 ml/min/kg; p <
      0.001), but when RIF was coadministered in the induced rats, digoxin clearance
      (7.14 +/- 1.24 ml/min/kg) overlapped with control. That is, concomitant dosing of
      RIF and digoxin masked the inductive effect. To observe full inductive effects,
      test drugs should be administered 1 day after final dosing of RIF to minimize
      potential organic anion transporting polypeptide inhibition effects.

PMID- 16905689
TI  - Proton pump inhibitors and gastric neoplasia.
AB  - Proton pump inhibitors (PPIs) are very effective in maintaining symptomatic and
      endoscopic remission of acid peptic disorders, such as gastro-oesophageal reflux
      disease. Side effects with respect to function and morphology of the gastric
      mucosa are common. Helicobacter pylori eradication can partially prevent and
      reverse these effects without impairing PPI therapy for gastro-oesophageal reflux
      disease. This makes long term PPI treatment a safe therapy for patients with acid
      peptic disorders. The potential side effects of such therapy are discussed here.

PMID- 16905690
TI  - Ablating Barrett's metaplastic epithelium: are the techniques ready for clinical
      use?

PMID- 16905691
TI  - Tacrolimus--finally!

PMID- 16905692
TI  - Role of interleukin 6 in a murine model of Crohn's ileitis: are
      cytokine/anticytokine strategies the future for IBD therapies?
AB  - Although the precise causes of inflammatory bowel disease (IBD) have yet to be
      discovered, important therapeutic advances have resulted from the manipulation of
      cytokine function(s) using anticytokine/cytokine therapies, such as targeting of
      tumor necrosis factor. We discuss the future of this area of investigation in the
      context of preclinical experimentation using animal models of IBD. In particular,
      we pinpoint the roles played by interleukin 6 and its intracellular signalling
      pathways in the SAMP1/Yit murine model of Crohn's-like ileitis.

PMID- 16905693
TI  - Human pancreatitis and the role of cathepsin B.

PMID- 16905694
TI  - Role of endothelin in systemic and portal resistance in cirrhosis.

PMID- 16905696
TI  - Catastrophic lower gastrointestinal complications following spinal surgery.

PMID- 16905698
TI  - Tracheal-oesophageal fistula in a patient with lung cancer.

PMID- 16905695
TI  - A randomised controlled trial of ablation of Barrett's oesophagus with multipolar
      electrocoagulation versus argon plasma coagulation in combination with acid
      suppression: long term results.
AB  - BACKGROUND: Many modalities have been used to ablate Barrett's oesophagus (BO).
      However, long term results and comparative effectiveness are unknown. AIMS: Our
      aim was to compare the long term efficacy of achieving complete reversal
      (endoscopic and histological) between multipolar electrocoagulation (MPEC) and
      argon plasma coagulation (APC) in BO patients and assess factors influencing
      successful ablation. METHODS: Patients with BO, 2-6 cm long, underwent 24 hour pH
      testing on proton pump inhibitor (PPI) therapy. Patients were then randomised by
      BO length to undergo ablation with MPEC or APC every 4-8 weeks until endoscopic
      reversal or maximal of six treatment sessions. RESULTS: Thirty five BO patients
      have been followed for at least two years following endoscopic ablation, 16
      treated with MPEC and 19 with APC. There was complete reversal of BO in 24
      patients (69%); 75% with MPEC and 63% with APC (p = 0.49). There was no
      difference in the number of sessions required in the two groups. There was no
      difference in age, pH results, BO length, PPI dose, or hiatal hernia size between
      patients with and without complete reversal. One patient developed an oesophageal
      stricture but there were no major complications such as bleeding or perforation.
      CONCLUSIONS: In BO patients treated with MPEC or APC in combination with acid
      suppression, at long term follow up, complete reversal of BO can be maintained in
      approximately 70% of patients, irrespective of the technique. There are no
      predictors associated with achieving complete reversal of BO. Continued
      surveillance is still indicated in the post ablative setting. As yet, these
      techniques are not ready for clinical application (other than for high grade
      dysplasia or early oesophageal adenocarcinoma) and cannot be offered outside the
      research arena.

PMID- 16905697
TI  - Recurrent gastrointestinal haemorrhage from the distal duodenum.

PMID- 16905699
TI  - An infrequent cause of gastrointestinal bleeding.

PMID- 16905700
TI  - PPARgamma as a new therapeutic target in inflammatory bowel diseases.
AB  - The peroxisome proliferator activated receptor gamma(PPARgamma) is a nuclear
      receptor highly expressed in the colon and playing a key role in bacterial
      induced inflammation. Regulation of colon inflammation by this receptor has been
      well demonstrated in many experimental models of colitis but also in patients
      with ulcerative colitis, characterised by impaired expression of PPARgamma
      confined to their colon epithelial cells. Recent data showing that PPARgamma was
      the major functional receptor mediating the common aminosalicylate activities in
      inflammatory bowel diseases (IBD) have also reinforced the roles of this receptor
      in the control of intestinal inflammation. The aims of this review are to discuss
      the potential roles of PPARgamma in the physiopathology of IBD, as well as the
      emerging therapeutic strategies targeting this receptor.

PMID- 16905702
TI  - Helicobacter pylori outer membrane proteins and gastric inflammation.

PMID- 16905703
TI  - Severe self limiting sclerosing cholangitis after pancreaticoduodenectomy due to
      autoimmune pancreatitis.

PMID- 16905701
TI  - Treating viral hepatitis C: efficacy, side effects, and complications.
AB  - The treatment of hepatitis C has dramatically improved over the past decade.
      Unlike any other chronic viral infection, a significant proportion of patients
      with chronic hepatitis C can be cured. However, the current standard therapy-
      pegylated interferon alpha and ribavirin--has its limitations. Limited efficacy
      in patients with hepatitis C virus (HCV) genotype 1 and the side effect profile
      will necessitate the development of new therapeutic approaches. This review
      describes the efficacy and optimisation of the current standard therapy of
      hepatitis C and its problems in special patient populations. New treatment
      directions beyond interferon alpha based therapies are on the horizon.

PMID- 16905704
TI  - Disappointing results of combination therapy for HCV?

PMID- 16905705
TI  - Leukotriene receptor antagonists as potential steroid sparing agents in a patient
      with serosal eosinophilic gastroenteritis.

PMID- 16905706
TI  - Prevention of abortion by ciclosporin treatment of fulminant ulcerative colitis
      during pregnancy.

PMID- 16905707
TI  - Effect of MRCP introduction on ERCP practice: are there implications for service
      and training?

PMID- 16905708
TI  - A novel method to determine small intestinal barrier function in human neonates
      in vivo.

PMID- 16905709
TI  - Genetic association of Fc receptor-like 3 polymorphisms with autoimmune
      pancreatitis in Japanese patients.

PMID- 16905710
TI  - Extensive intestinal ischaemic necrosis in Wegener's granulomatosis.

PMID- 16905711
TI  - Elevated CD4+/CD25+ T cell frequency and function during acute hepatitis C
      presage chronic evolution.

PMID- 16905712
TI  - Thalidomide in refractory haemorrhagic radiation induced proctitis.

PMID- 16905713
TI  - A case of rheumatoid arthritis with protein losing enteropathy induced by
      multiple diaphragmatic strictures of the small intestine: successful treatment by
      bougieing under double-balloon enteroscopy.

PMID- 16905714
TI  - Comparing the part with the whole: should overlap be ignored in public health
      measures?
AB  - BACKGROUND: In public health, health outcomes such as cancer incidence or
      mortality of subgroups are often compared with health outcomes of the whole
      population. Our objective was to explore the effect of overlap that occurs in
      such comparisons and to develop a correction factor to adjust the test statistics
      and confidence intervals to allow for the effect in situations where the full
      data are not available. METHOD: The standard error of a difference between a
      statistic calculated for a subgroup and for the whole population was derived
      theoretically both ignoring and allowing for overlap. The ratio of these standard
      errors was defined as the correction factor. Cancer incidence and death data
      (1997-2001) for the Australian state of New South Wales (NSW) were examined to
      demonstrate the utility of the correction factor. RESULTS: If the overlap is
      ignored, significance tests are conservative and confidence intervals too wide.
      In an example with an overlap of 12%, the correction factor was 1.13 and the
      significance level of 0.08 was corrected to 0.05 by taking the overlap into
      account. CONCLUSIONS: The overlap may not be of concern if the result is
      significant or if the subgroup is <10% of the whole population, but if the
      overlap is greater than 10% it should not be ignored. The easiest way of allowing
      for overlap is to use a correction factor, calculated from the amount of overlap,
      to adjust analyses that ignore overlap.

PMID- 16905715
TI  - Glossary on the World Trade Organisation and public health: part 2.
AB  - Part 1 of this glossary introduced different health and trade arguments,
      overviewed the history of the World Trade Organisation (WTO), defined key "trade
      talk" terms, and reviewed three WTO treaties concerned with trade in goods (GATT
      1994, the Agreement on Agriculture, and the Agreement on Sanitary and
      Phytosanitary Measures). Part 2 reviews five more agreements and the growing
      number of bilateral and regional trade agreements, and concludes with a
      commentary on different strategies proposed to ensure that health is not
      compromised by trade liberalization treaties.

PMID- 16905716
TI  - Perceived causes of sporadic cryptosporidiosis and their relation to sources of
      information.
AB  - BACKGROUND: The importance of a person's perceptions about the causes of their
      disease has been emphasised by research on various diseases. Several studies have
      found perception may be linked to protective behaviours. OBJECTIVE: This study
      intends to identify the main perceived causes of sporadic cryptosporidiosis, and
      to analyse some of the factors that may influence respondent's perception. The
      role of respondents' attributions, the scientific plausibility of perceptions,
      and the importance of specific information sources are also explored. DESIGN:
      Quantitative and qualitative analyses of data from a case-control study. SETTING:
      General population in Wales and north west England. PARTICIPANTS: The study is
      based on a sample of 411 respondents from Wales and north west of England, whose
      cryptosporidiosis diagnosis was confirmed by a laboratory. RESULTS: The results
      show that the most frequent perceived causes are water (by drinking it or
      swimming), contagion (mostly from children), and contaminated food. Perceived
      causes are qualitatively similar to the ones described in scientific literature,
      but some quantitative differences are evident. Respondents' certainty in relation
      to the cause of illness is directly related with plausibility. The most frequent
      information sources used by respondents were test stool results, environmental
      health officers, and doctors or nurses. Results suggest that information sources
      may influence the perception of the causes of cryptosporidiosis. Qualitative data
      provided a few clues about situations where sporadic and outbreak cases may be
      confused. CONCLUSION: In contrast with outbreaks, various information sources in
      addition to the media are used by people with sporadic cryptosporidiosis that in
      turn affects the perception of aetiology. This has implications for the
      dissemination of information about control measures for cryptosporidiosis and
      surveillance activities.

PMID- 16905717
TI  - Health treaty dilution: a case study of Japan's influence on the language of the
      WHO Framework Convention on Tobacco Control.
AB  - BACKGROUND: The Japanese government is an important shareholder in the Japanese
      tobacco industry. Negotiations to develop the WHO's historic Framework Convention
      on Tobacco Control (FCTC) were based on consensus, resulting in countries needing
      to agree to the lowest acceptable common denominator in clause development.
      OBJECTIVE: To illustrate Japan's role in negotiating key optional language in the
      FCTC text. METHODS: Summary reports, text proposals, conference papers, and
      speeches related to the six FCTC negotiation sessions were reviewed for repeated
      words, concepts and emerging themes. Key stakeholders were interviewed. Key words
      such as "sovereignty", "appropriate", "latitude", "individual", "flexibility",
      and "may" representing optional language were examined. RESULTS: The Japanese
      government's proposals for "appropriate" and optional measures are reflected in
      the final FCTC text that accommodates flexibility on interpretation and
      implementation on key tobacco controls. While Japan was not alone in proposing
      optional language, consensus accommodated their proposals. CONCLUSION: Japan's
      success in arguing for extensive optional language seriously weakened the FCTC.
      Accordingly, international tobacco control can be expected to be less successful
      in reducing the burden of disease caused by tobacco use.

PMID- 16905718
TI  - Some doubts about one of the largest smoking prevention programmes in Europe, the
      smokefree class competition.
AB  - With over 600,000 participants in 16 countries, the smokefree class competition
      is one of the largest smoking prevention programmes in Europe. Participating
      classes that maintain a smoking prevalence usually below 10% are eligible for a
      contest and the winner is rewarded with money. There is however no convincing
      evidence that this competition has any effect on smoking prevalence beyond the
      short term, and this approach raises serious ethical issues. In particular, the
      central principle of this competition is to apply negative peer pressure upon
      teenage smokers. However, promoters of this competition have neglected to report
      the possible adverse consequences of using negative peer pressure upon smokers.
      This is a concern, because teenage smokers are more vulnerable than non-smokers,
      and they are at higher risk of suffering from psychological problems and school
      failure.

PMID- 16905719
TI  - Marital status and longevity in the United States population.
AB  - PURPOSE: To investigate the relation between marital status and survival. DATA
      SOURCES: The US 1989 national health interview survey (NHIS) merged with the 1997
      US national death index. RESULTS: Among 1989 NHIS respondents, 5876 (8.77%) died
      before 1997 and 61 123 (91.23%) were known to be alive. Controlling for
      demographic and socioeconomic characteristics, the death rate for people who were
      unmarried was significantly higher than it was for those who were married and
      living with their spouses. Although the effect was significant for all categories
      of unmarried, it was strongest for those who had never married. The never married
      effect was seen for both sexes, and was significantly stronger for men than for
      women. For the youngest age group (19-44), the predominant causes of early death
      among adults who had never married were infectious disease (presumably HIV) and
      external causes. In the middle aged and older men and women, the predominant
      causes were cardiovascular and other chronic diseases. CONCLUSION: Current
      marriage is associated with longer survival. Among the not married categories,
      having never been married was the strongest predictor of premature mortality. It
      is difficult to assess the causal effect of marital status from these
      observational data.

PMID- 16905720
TI  - Social context and depression after a disaster: the role of income inequality.
AB  - STUDY OBJECTIVE: To examine the association between neighbourhood income
      inequality and depression, both overall and among those with different levels of
      income, in the post-disaster context. DESIGN: A representative cross sectional
      random digit dial telephone survey was conducted. SETTING: New York City (NYC)
      six months after September 11, 2001. PARTICIPANTS: 1570 respondents were
      interviewed, of whom 1355 provided residence information permitting their
      inclusion in this analysis. Past six month depression was assessed using a lay
      administered instrument consistent with DSM-IV criteria. Income inequality was
      measured with the Gini coefficient. MAIN RESULTS: The sample was demographically
      representative of NYC (56.2% female, 35.7% white, 6.3% Asian 24.2% African
      American, 29.7% Hispanic, and 4.2% other race or ethnicity) and the prevalence of
      past six month depression was 12.4%. In a final adjusted model, neighbourhood
      level income inequality was positively associated with depression but this
      association was not significant (beta = 7.58, p = 0.1). However, among those with
      low individual income (< 20,000 US dollars) there was a strong significant
      association between income inequality and depression (beta = 35.02, p<0.01),
      while there was no association among those with higher income. CONCLUSIONS: In
      the post-disaster context, neighbourhood level income inequality was associated
      with depression among persons with lower income; this group may be more socially
      or economically marginalized and dependent on local resources. Future research
      should examine potential mechanisms through which income inequality and other
      features of the social context may affect mental health in the post-disaster
      context.

PMID- 16905721
TI  - Work related violence and threats and the risk of depression and stress
      disorders.
AB  - OBJECTIVE: To examine the risk of depression and stress related disorders as a
      function of occupational exposure to violence and threats. DESIGN: Population
      based nested case-control study. SETTING: All gainfully employed Danes. Cases and
      controls: 14 166 hospital inpatients and outpatients, aged 18-65, treated for
      affective or stress related disorders during 1995-1998 selected from The Danish
      Psychiatric Central Research Register and 58 060 controls matched for age, sex,
      and time, drawn from Statistics Denmark's Integrated Database for Labour Market
      Research. MAIN OUTCOME MEASURE: Clinical psychiatric diagnosis (WHO ICD-10) of
      affective (F30-39) or stress related (F40-48) disorders compared with controls by
      the occupation held the year before treatment. The occupation held the year
      before treatment was used as exposure proxy. RESULTS: Potential exposure to
      occupational violence is associated with significantly increased relative risks
      of both disorders in either sex (women: depression RR 1.45 CI 1.27 to 1.65,
      stress RR 1.32 CI 1.19 to 1.46; men: depression RR 1.48 CI 1.18 to 1.86, stress
      RR 1.55 CI 1.29 to 1.84). Work related threats are associated with increase in
      the risk of depression in women (RR 1.48 CI 1.23 to 1.79) and the risk of stress
      related disorders in men (RR 1.59 CI 1.32 to 1.91). Risks rose with increasing
      prevalence of violence and threats. The results remain significant and only
      slightly attenuated after controlling for extent of professional contact with
      people other than colleagues. CONCLUSIONS: Employment in occupations involving
      exposure to work related threats and violence is a risk factor for depression and
      stress related disorders in both sexes. These findings have implications for
      health and safety at work policies.

PMID- 16905722
TI  - Psychiatric illness, socioeconomic status, and marital status in people
      committing suicide: a matched case-sibling-control study.
AB  - STUDY OBJECTIVE: Suicides cluster in both families and persons with psychiatric
      disorders and socioeconomic disadvantages. This study compares these factors
      between suicide cases, their siblings, and population based controls in an
      attempt to evaluate both the familial and the individual element of these
      factors. DESIGN: Nested case-control study. Information on causes of death,
      psychiatric admission, marital status, children, and socioeconomic factors was
      obtained from routine registers. SETTING: Denmark. PARTICIPANTS: 985 suicide
      cases, 1104 sex-age (+/-3 years) matched siblings, and 16 619 controls. MAIN
      RESULTS: The suicide rate ratios obtained from the case-sibling and the case
      control analysis, respectively, were of similar magnitude. For example, in the
      case-sibling analysis the adjusted suicide rate ratios associated with discharge
      from a psychiatric hospital within the previous 365 days, being unemployed the
      previous year, having a postgraduate degree and being single were 42.13 (95% CI
      17.75 to 100.02), 1.78 (1.35 to 2.36), 0.51 (0.21 to 1.26), and 2.69 (1.91 to
      3.79), respectively. The corresponding rate ratios obtained from the case-control
      analysis were 47.91 (35.41 to 64.83), 1.76 (1.49 to 2.08), 0.45 (0.26 to 0.76),
      and 2.39 (1.87 to 3.07). Moreover, the analogous ratios when comparing siblings
      and controls were 1.98 (1.08 to 3.63), 1.22 (1.06 to 1.41), 0.65 (0.44 to 0.95),
      and 0.89 (0.75 to 1.06). CONCLUSIONS: People who commit suicide deviate similarly
      from siblings and controls in exposure to hospitalised psychiatric disorders and
      socioeconomic disadvantages, although these factors contribute to the familial
      aggregation of suicides.

PMID- 16905723
TI  - Psychosocial determinants of premature cardiovascular mortality differences
      within Hungary.
AB  - OBJECTIVES: The life expectancy gap between Central-Eastern European (CEE)
      countries, including Hungary, and Western Europe (WE) is mainly attributable to
      excess cardiovascular (CV) mortality in midlife. This study explores the
      contribution of socioeconomic, work related, psychosocial, and behavioural
      variables to explaining variations of middle aged male and female CV mortality
      across 150 sub-regions in Hungary. DESIGN: Cross sectional, ecological analyses.
      SETTING: 150 sub-regions of Hungary. PARTICIPANTS AND METHODS: 12 643 people were
      interviewed in Hungarostudy 2002 survey, representing the Hungarian population
      according to sex, age, and sub-regions. Independent variables were income,
      education, control in work, job insecurity, weekend working hours, social
      support, depression, hostility, anomie, smoking, body mass index, and alcohol
      misuse. MAIN OUTCOME MEASURES: Gender specific standardised premature (45-64
      years) total CV, ischaemic heart disease, and cerebrovascular mortality rates in
      150 sub-regions of Hungary. RESULTS: Low education and income were the most
      important determinants of mid-aged CV mortality differences across sub-regions.
      High weekend workload, low social support at work, and low control at work
      account for a large part of variation in male premature CV mortality rates,
      whereas job insecurity, high weekend workload, and low control at work contribute
      most noticeably to variations in premature CV mortality rates among women. Low
      social support from friends, depression, anomie, hostility, alcohol misuse and
      cigarette smoking can also explain a considerable part of variations of premature
      CV mortality differences. CONCLUSION: Variations in middle aged CV mortality
      rates in a rapidly changing society in CEE are largely accounted for by distinct
      unfavourable working and other psychosocial stress conditions.

PMID- 16905724
TI  - Psychological distress and chronic obstructive pulmonary disease in the Renfrew
      and Paisley (MIDSPAN) study.
AB  - BACKGROUND: This study examined whether psychological distress might be a
      predictor of chronic obstructive pulmonary disease (COPD). METHOD: The relation
      between psychological distress at baseline, measured by the general health
      questionnaire (GHQ), and chronic bronchitis three years later, as measured by the
      Medical Research Council (MRC) bronchitis questionnaire and forced expiratory
      flow in one second (FEV(1)), was examined in 1682 men and 2203 women from the
      Renfrew and Paisley (MIDSPAN) study. The analyses were run on men and women
      separately and adjustments were made for age, socioeconomic position, and lung
      function at baseline (FEV(1)). People with chronic diseases at baseline were then
      excluded to give a "healthy" baseline cohort. The effect of psychological
      distress on individual components of the MRC bronchitis questionnaire and FEV(1)
      was also assessed. RESULTS: In multivariate analyses of the whole cohort baseline
      psychological distress in women was associated with reduced FEV(1) at follow up
      (OR 1.31 95% CI 1.0 to 1.73) after adjustment. In women, in the healthy cohort,
      psychological distress was associated with chronic bronchitis (OR 2.00, 95% CI
      1.16 to 3.46), symptoms of bronchial infection (OR 2.14, 95% CI 1.44 to 3.19),
      symptoms of breathlessness (OR 3.02, 95% CI 1.99 to 4.59), and reduced FEV(1) (OR
      1.62, 95% CI 1.13 to 2.32). In men psychological distress predicted symptoms of
      bronchial infection (OR 2.09, 95% CI 1.28 to 3.42). CONCLUSION: This study
      supports research suggesting that psychological distress is associated with COPD
      and shows that psychological distress predicts COPD in women. The robustness of
      the association and the exact mechanism requires further investigation.

PMID- 16905726
TI  - Smoking trends in Italy from 1950 to 2000.
AB  - STUDY OBJECTIVE: To assess how the prevalence of smokers in Italy from 1950 to
      2000 has changed, in parallel with law development and the growing attention
      towards smoking prevention. DESIGN, SETTING, AND PARTICIPANTS: Historical data on
      smoking trends have been obtained using data collected in 2000 by the National
      Institute of Statistics. A correction coefficient is proposed to overcome the
      bias of differential mortality reported in other papers. The sample is made up of
      102 261 people aged 15-69 years. MAIN RESULTS: A general downward trend is seen;
      there is a more pronounced decrease starting from 1975 to 1980. In both sexes the
      peak prevalence tends to decrease according to the birth cohort because of the
      earlier age in which they gave up. A partial exception to the decline of tobacco
      use in recent years may be made for the 15-19 year-old age group, which has
      remained stable since 1990. CONCLUSIONS: Although a comprehensive community
      programme against tobacco was not developed, the different prevention actions
      implemented in Italy have contributed to a change in attitude and behaviour. The
      effect of tobacco control strategies implemented in Italy until now is more
      evident in relation to the breaking of the smoking habit, which happens at an
      increasingly younger age, although it is not clear how much it is able to prevent
      people from starting smoking.

PMID- 16905725
TI  - Pain and health related functioning among employees.
AB  - STUDY OBJECTIVE: Although employees report high rates of pain, little is known
      about the effects of pain on health related functioning among them. This study
      examined the effects of pain on employees' health related functioning by bodily
      locations of pain, number of painful locations, and whether pain was acute or
      chronic. DESIGN: Cross sectional questionnaire survey. Data on pain and health
      related functioning as measured with the eight subscales of the short form 36
      health survey (SF-36) were obtained in the years 2001 and 2002. SETTING:
      Municipal employees of the City of Helsinki, Finland. PARTICIPANTS: All employees
      who reached the age of 40, 45, 50, 55, and 60 years during each study year.
      Response rate was 66% (n = 5829). MAIN RESULTS: Compared with those reporting no
      pain, those with pain had considerably poorer functioning on all SF-36 subscales.
      The lowest scores for health related functioning were seen in the physical domain
      of health, whereas the mental domain was less affected. The association of pain
      with functioning was practically independent of the bodily location of pain.
      Whether pain was acute or chronic had only a modest effect on functioning. Widest
      variation in functioning was found by the number of painful locations.
      CONCLUSIONS: Among employees pain complaints, irrespective of the location, are
      associated with a decreased level of functioning. The number of painful locations
      is likely to be the most useful measure to identify employees with a high risk of
      poor functioning.

PMID- 16905727
TI  - Education, income, and occupational class cannot be used interchangeably in
      social epidemiology. Empirical evidence against a common practice.
AB  - STUDY OBJECTIVE: Education, income, and occupational class are often used
      interchangeably in studies showing social inequalities in health. This procedure
      implies that all three characteristics measure the same underlying phenomena.
      This paper questions this practice. The study looked for any independent effects
      of education, income, and occupational class on four health outcomes: diabetes
      prevalence, myocardial infarction incidence and mortality, and finally all cause
      mortality in populations from Sweden and Germany. DESIGN: Sweden: follow up of
      myocardial infarction mortality and all cause mortality in the entire population,
      based on census linkage to the Cause of Death Registry. Germany: follow up of
      myocardial infarction morbidity and all cause mortality in statutory health
      insurance data, plus analysis of prevalence data on diabetes. Multiple regression
      analyses were performed to calculate the effects of education, income, and
      occupational class before and after mutual adjustments. SETTING AND PARTICIPANTS:
      Sweden (all residents aged 25-64) and Germany (Mettman district, Nordrhein
      Westfalen, all insured persons aged 25-64). MAIN RESULTS: Correlations between
      education, income, and occupational class were low to moderate. Which of these
      yielded the strongest effects on health depended on type of health outcome in
      question. For diabetes, education was the strongest predictor and for all cause
      mortality it was income. Myocardial infarction morbidity and mortality showed a
      more mixed picture. In mutually adjusted analyses each social dimension had an
      independent effect on each health outcome in both countries. CONCLUSIONS:
      Education, income, and occupational class cannot be used interchangeably as
      indicators of a hypothetical latent social dimension. Although correlated, they
      measure different phenomena and tap into different causal mechanisms.

PMID- 16905730
TI  - Emerging issues in public health information.

PMID- 16905729
TI  - Is an internal comparison better than using national data when estimating
      mortality in longitudinal studies?
AB  - BACKGROUND: Discrepancies between the results of different studies looking at
      mortality in similar disease cohorts led us to consider the impact of methodology
      upon outcome. METHODS: Cohort studies were carried out using age, sex, practice,
      and calendar time matched control groups in the general practice research
      database. Data were used on all subjects with inflammatory bowel disease, coeliac
      disease, or Barrett's oesophagus. Mortality data for the population of England
      and Wales were obtained from the UK Office for National Statistics. The study
      compared hazard ratios (HR) for mortality using the matched controls to those
      found when an indirect standardisation to the mortality experience of England and
      Wales was carried out. RESULTS: For all three conditions the mortality risk was
      slightly lower when the national population data were used compared with the
      internal comparison group (coeliac disease HR 1.33 v standardised mortality
      ratios (SMR) 1.25, Barrett's oesophagus HR 1.32 v SMR 1.32, inflammatory bowel
      disease HR 1.50 v SMR 1.34). CONCLUSIONS: A bias was found towards
      underestimating mortality risk when cohort studies use national population death
      rates as a comparator. Estimates obtained when an internal comparison group has
      been used are probably more appropriate.

PMID- 16905728
TI  - Bimodal virological response to antiretroviral therapy for HIV infection: an
      application using a mixture model with left censoring.
AB  - STUDY OBJECTIVE: To assess whether HIV RNA levels (log(10) scale) in highly
      active antiretroviral therapy (HAART) treated population have a bimodal
      distribution, suggesting optimal or suboptimal response to HAART. METHODS: The
      study population from two ongoing cohort studies comprised 564 men (4785 person
      visits) and 1173 women (8675 person visits) with known dates of HAART initiation
      and with HIV RNA measurements before and after initiation. Values below detection
      limit of assays were treated in the analysis as left censored. Maximum likelihood
      methods were used to estimate parameters and to determine possible bimodality of
      HIV RNA distributions. RESULTS: A two component mixture model fitted HIV RNA
      levels significantly better than did a single component distribution at different
      years from HAART initiation in both therapy experienced and therapy naive
      patients. In the fifth year after HAART initiation, 32% of men and 44% of women
      had HIV RNA in the higher component with medians of 5247 and 9253 copies/ml,
      respectively, suggesting suboptimal virological response to HAART, which was
      associated with poor adherence and lower frequency of CCR5 heterozygous genotype.
      CONCLUSION: The bimodal distribution of HIV RNA persisted during the years after
      HAART initiation. The high occurrence of suboptimal virological response at the
      fifth year after HAART initiation underscore the needs for careful monitoring and
      patient education about the importance of treatment adherence. This data analysis
      overcomes limitations of measurement techniques of observations having values
      below detection limits and serves to characterise the dynamics of the virological
      response to therapies.

PMID- 16905732
TI  - Fate of cystic ovarian follicles and the subsequent fertility of early postpartum
      dairy cows.
AB  - The fate of cystic ovarian follicles that developed spontaneously during the
      early postpartum period of 50 lactating dairy cows was traced by ultrasonography
      to characterise the follicular dynamics in relation to the fertility of the cows.
      The absence of postpartum ovulations caused by repeated waves of anovulatory
      large follicles was also characterised and evaluated. Fifteen of the 50 cows
      developed cystic follicles, and these follicles became follicular cysts in five
      of the 15 cows. Most of the cystic follicles emerged before the first postpartum
      ovulation of the cows. The transition from cystic follicles to follicular cysts
      delayed the cows' first ovulation, oestrus and insemination, but had less
      influence on their fertility after they had recovered spontaneously. In addition
      to the 15 cows that developed cystic follicles or follicular cysts, six of the
      cows had five to 13 waves of follicles before their first ovulation. These
      repeated waves of follicles caused a more severe delay in the early postpartum
      reproductive events but did not affect the cows' fertility.

PMID- 16905731
TI  - Factors associated with preweaning mortality on commercial pig farms in England
      and Wales.
AB  - Data from 67 pig farms with a variety of farrowing systems were used to identify
      factors associated with preweaning mortality in British pig herds. The median
      mortality reported by the farmers was 10.7 per cent (interquartile range 8.5 to
      14 per cent). There was a significantly higher mortality when the pigs were
      weaned when they were older. A multivariable Poisson model was developed into
      which the types of farrowing system on each farm and the age at weaning were
      forced. Factors associated with a lower preweaning mortality rate were insulating
      the farrowing building, providing extra heat at farrowing, giving the piglets
      iron injections, dipping their navels, using fan ventilation and using artificial
      lighting systems. Factors associated with a higher mortality rate were a later
      weaning age, the use of infra-red lamps rather than other forms of supplementary
      heat, and the use of a creep without any bedding.

PMID- 16905733
TI  - Hepatozoon species infection in wild red squirrels (Sciurus vulgaris) on the Isle
      of Wight.
AB  - Postmortem examinations of 49 red squirrels (Sciurus vulgaris) found dead on the
      Isle of Wight revealed the presence of a Hepatozoon species in 18 of them (37 per
      cent). The prevalence of infection was highest in subadult animals and no
      juveniles were infected. The prevalence was higher in the squirrels dying from
      natural causes (nine of 12) than in squirrels killed in road accidents (seven of
      27). The weight of infection varied, and there were heavy infections in squirrels
      dying from toxoplasmosis and bacterial pneumonia. A PCR-based assay was used to
      identify the presence of Hepatozoon species DNA in the lungs, and
      immunoperoxidase staining was used to confirm the identity of schizonts observed
      in histological sections. The nucleotide base sequence of the PCR products
      indicated that the organism was a novel species closely related to, but distinct
      from, Hepatozoon erhardovae of bank voles (Clethrionomys glareolus).

PMID- 16905734
TI  - Evaluation of a spray of permethrin and pyriproxyfen for the protection of dogs
      against Phlebotomus perniciosus.
AB  - Dogs are the main domestic reservoir of Leishmania infantum in the Old World
      (Leishmania chagasi in the New World) a parasite responsible for many cases of
      human visceral leishmaniasis in both endemic and non-endemic regions. One
      strategy for the control of leishmaniasis would be to prevent dogs from being
      bitten by sandflies, the vector of leishmaniasis. This study was designed to
      assess the efficacy of spraying a combination of permethrin and pyriproxyfen on
      to dogs artificially exposed to sandflies. Two groups of four male dogs, one of
      them treated and the other left untreated as controls, were exposed for one hour
      to 100 female sandflies seven days before the treatment, on the day of treatment
      and seven, 14, 21, and 28 days later. After each exposure, sandflies were
      collected, counted and scored. The prevention of sandfly bite was calculated by
      measuring the number of fed sandflies (dead and alive) after treatment. In this
      experimental assay, the repellent effect of the treatment against sandfly bites
      after 21 days was 71.4 per cent, but the insecticidal effect was only 7.2 per
      cent.

PMID- 16905735
TI  - Poult enteritis and mortality syndrome in turkeys in Great Britain.

PMID- 16905736
TI  - Cutaneous teratoma in a wild roe deer (Capreolus capreolus) in the UK.

PMID- 16905737
TI  - Identification of circovirus infection in three species of gull.

PMID- 16905738
TI  - Asymptomatic cystic calculus in a two-toed sloth (Choloepus didactylus).

PMID- 16905739
TI  - Clinical efficacy of rifamycin SV combined with oxytetracycline in the treatment
      of caseous lymphadenitis in sheep.

PMID- 16905740
TI  - Trade in wild birds.

PMID- 16905741
TI  - Use of authorised veterinary medicinal products.

PMID- 16905742
TI  - Badger culling consultation.

PMID- 16905743
TI  - TB policy and the badger culling trials.

PMID- 16905744
TI  - CXCL12 induces tyrosine phosphorylation of cortactin, which plays a role in CXC
      chemokine receptor 4-mediated extracellular signal-regulated kinase activation
      and chemotaxis.
AB  - CXC chemokine receptor 4 (CXCR4) plays a role in the development of immune and
      central nervous systems as well as in cancer growth and metastasis. CXCR4
      initiated signaling cascades leading to cell proliferation and chemotaxis are
      critical for these functions. The present study demonstrated that stimulation of
      CXCR4 by its ligand, CXCL12, induced transient translocation of cortactin from
      endosomal compartments to the cell periphery where it colocalized with CXCR4
      followed by internalization of CXCR4 together with cortactin into endosomes.
      Cortactin was co-immunoprecipitated with CXCR4 in response to CXCL12 treatment in
      a time-dependent manner. Ligand stimulation induced phosphorylation of cortactin
      at tyrosine 421, and the phosphorylation was both c-Src- and dynamin-dependent.
      Cortactin overexpression promoted CXCR4 internalization and recycling. However,
      overexpression of a cortactin mutant in which tyrosine 421 was replaced with
      alanine (cortactin-Y421A) or knockdown of cortactin with RNA interference (RNAi)
      reduced CXCR4 internalization in response to CXCL12. CXCR4-mediated activation of
      extracellular signal-regulated kinases 1 and 2 was significantly prolonged by
      overexpression of wild-type cortactin but not by the cortactin-Y421A mutant and
      was inhibited by cortactin knockdown with RNAi. Moreover, CXCL12-induced
      chemotaxis was enhanced by cortactin overexpression, reduced by overexpression of
      the cortactin-Y421A mutant, and blocked by cortactin knockdown with RNAi. These
      data provide strong evidence for an important role of cortactin in CXCR4
      signaling and trafficking as well in the receptor-mediated cell migration.

PMID- 16905745
TI  - An intermediate pH unfolding transition abrogates the ability of IgE to interact
      with its high affinity receptor FcepsilonRIalpha.
AB  - The interaction between IgE-Fc (Fcepsilon) and its high affinity receptor
      FcepsilonRI on the surface of mast cells and basophils is a key event in allergen
      induced allergic inflammation. Recently, several therapeutic strategies have been
      developed based on this interaction, and some include Fcepsilon-containing
      moieties. Unlike well characterized IgG therapeutics, the stability and folding
      properties of IgE are not well understood. Here, we present comparative
      biophysical analyses of the pH stability and thermostability of Fcepsilon and
      IgG1-Fc (Fcgamma). Fcepsilon was found to be significantly less stable than
      Fcgamma under all pH and NaCl conditions tested. Additionally, the
      Cepsilon3Cepsilon4 domains of Fcepsilon were shown to become intrinsically
      unfolded at pH values below 5.0. The interaction between Fcepsilon and an Fcgamma
      FcepsilonRIalpha fusion protein was studied between pH 4.5 and 7.4 using circular
      dichroism and a combination of differential scanning calorimetry and isothermal
      titration calorimetry. Under neutral pH conditions, the apparent affinity of
      Fcepsilon for the dimeric fusion protein was extremely high compared with
      published values for the monomeric receptor (KD < 10(-12) m). Titration to pH 6.0
      did not significantly change the binding affinity, and titration to pH 5.5 only
      modestly attenuated affinity. At pH values below 5.0, the receptor binding
      domains of Fcepsilon unfolded, and interaction of Fcepsilon with the Fcgamma
      FcepsilonRIalpha fusion protein was abrogated. The unusual pH sensitivity of
      Fcepsilon may play a role in antigen-dependent regulation of receptor-bound, non
      circulating IgE.

PMID- 16905746
TI  - Saposin A mobilizes lipids from low cholesterol and high
      bis(monoacylglycerol)phosphate-containing membranes: patient variant Saposin A
      lacks lipid extraction capacity.
AB  - Saposin A (Sap-A) is one of five known sphingolipid activator proteins required
      for the lysosomal degradation of sphingolipids and for the loading of lipid
      antigens onto antigen-presenting molecules of the CD1 type. Sap-A assists in the
      degradation of galactosylceramide by galactosylceramide-beta-galactosidase in
      vivo, which takes place at the surface of intraendosomal/intralysosomal vesicles.
      Sap-A is believed to mediate the interaction between the enzyme and its membrane
      bound substrate. Its dysfunction causes a variant form of Krabbe disease. In the
      present study we prepared glycosylated Sap-A free of other Saps, taking advantage
      of the Pichia pastoris expression system. Using liposomes and surface plasmon
      resonance spectroscopy, we tested the binding and lipid mobilization capacity of
      Sap-A under different conditions. Along the endocytic pathway, the pH value
      decreases, and the lipid composition of intraendosomal and intralysosomal
      membranes changes drastically. In the inner membranes the cholesterol
      concentration decreases, and that of the anionic phospholipid
      bis(monoacylglycero)phosphate increases. Here, we show that Sap-A is able to bind
      to liposomes and to mobilize lipids out of them at acidic pH values below pH 4.7.
      Low cholesterol levels and increasing concentrations of
      bis(monoacylglycero)phosphate favor lipid extraction significantly.
      Galactosylceramide as a bilayer component is not essential for lipid mobilization
      by Sap-A, which requires intact disulfide bridges for activity. We also show for
      the first time that glycosylation of Sap-A is essential for its lipid extraction
      activity. Variant Sap-A proteins, which cause storage of galactosylceramide in
      humans (Krabbe disease, Spiegel, R., Bach, G., Sury, V., Mengistu, G., Meidan,
      B., Shalev, S., Shneor, Y., Mandel, H., and Zeigler, M. (2005) Mol. Genet. Metab.
      84, 160-166) and in mutant mice (Matsuda, J., Vanier, M. T., Saito, Y., Tohyama,
      J., and Suzuki, K. (2001) Hum. Mol. Genet. 10, 1191-1199) are deficient in lipid
      extraction capacity.

PMID- 16905747
TI  - Identification of a tyrosine-based motif (YGSI) in the amino terminus of Nramp1
      (Slc11a1) that is important for lysosomal targeting.
AB  - In macrophages, Nramp1 (Slc11a1) is expressed in lysosomes and restricts
      replication of intracellular pathogens by removing divalent metals (Mn2+ and
      Fe2+) from the phagolysosome. Nramp2 (DMT1, Slc11a2) is expressed both at the
      duodenal brush border where it mediates uptake of dietary iron and ubiquitously
      at the plasma membrane/recycling endosomes of many cell types where it transports
      transferrin-associated iron across the endosomal membrane. In Nramp2, a carboxyl
      terminal cytoplasmic motif ((555)YLLNT(559)) is critical for internalization and
      recycling of the transporter from the plasma membrane. Here we studied the
      subcellular trafficking properties of Nramp1 and investigated the cis-acting
      sequences responsible for targeting to lysosomes. For this, we constructed and
      studied Nramp1/Nramp2 chimeric proteins where homologous domains of each protein
      were exchanged. Chimeras exchanging the amino-(upstream TM1) and carboxyl
      terminal (downstream TM12) cytoplasmic segments of both transporters were stably
      expressed in porcine LLC-PK1 kidney cells and were studied with respect to
      expression, maturation, stability, cell surface targeting, transport activity,
      and subcellular localization. An Nramp2 isoform II chimera bearing the amino
      terminus of Nramp1 was not expressed at the cell surface but was targeted to
      lysosomes. This lysosomal targeting was abolished by single alanine substitutions
      at Tyr15 and Ile18 of a (15)YGSI(18) motif present in the amino terminus of
      Nramp1. These results identify YGSI as a tyrosine-based sorting signal
      responsible for lysosomal targeting of Nramp1.

PMID- 16905748
TI  - Deoxycholic acid at neutral and acid pH, is genotoxic to oesophageal cells
      through the induction of ROS: The potential role of anti-oxidants in Barrett's
      oesophagus.
AB  - Bile acids are often refluxed into the lower oesophagus and are candidate
      carcinogens in the development of oesophageal adenocarcinoma. We show here that
      the secondary bile acid, deoxycholic acid (DCA), is the only one of the commonly
      refluxed bile acids tested here, to show genotoxicity, in terms of chromosome
      damage and mutation induction in the human p53 gene. This genotoxicity was
      apparent at both neutral and acidic pH, whilst there was a considerable increase
      in bile-induced toxicity at acidic pH. The higher levels of cell death and low
      cell survival rates at acidic pH may imply that acid bile exposure is toxic
      rather than carcinogenic, as dead cells do not seed cancer development. We also
      show that DCA (at neutral and acid pH) induced the release of reactive oxygen
      species (ROS) within the cytoplasm of exposed cells. We further demonstrate that
      the genotoxicity of DCA is ROS mediated, as micronucleus induction was
      significantly reduced when cells were treated with DCA + the anti-oxidant vitamin
      C. In conclusion, we show that DCA, is an effective genotoxin at both neutral and
      acidic pH. As bile acids like DCA can induce DNA damage at neutral pH,
      suppressing the acidity of the refluxate will not completely remove its
      carcinogenic potential. The genotoxicity of DCA is however, ROS dependent, hence
      anti-oxidant supplementation, in addition to acid suppression may block DCA
      driven carcinogenesis in Barrett's patients.

PMID- 16905749
TI  - The aetiology of deep venous thrombosis.
AB  - Most ideas about the pathogenesis of deep venous thrombosis (DVT) are dominated
      by a 'consensus model' first articulated around 1962. This model invokes
      'Virchow's triad' and attributes thrombogenesis in veins to some combination of
      'hypercoagulability', 'stasis' and 'intimal injury'. This arose as a by-product
      of studies on the mechanisms of haemostasis and bleeding diatheses that were at
      best only indirectly relevant to thrombosis, and there are reasons for doubting
      the causal significance of 'hypercoagulability' and 'stasis' in the aetiology of
      DVT. Proponents of the consensus model make little reference to a substantial
      literature, mostly historical, that: (a) emphasizes the significance of the
      venous valve pockets (VVP) and blood rheology in DVT pathogenesis; and (b)
      describes morphological features specific to venous thrombi that a valid
      aetiological model must explain. This literature provides the basis for an
      alternative hypothesis of DVT aetiology, published some 30 years ago, which has
      been experimentally corroborated and is compatible with recent cell and molecular
      biological studies of the venous endothelium. We review this alternative
      hypothesis, considering its potential value for future research on DVT and
      embolism, and its significance for clinical practice.

PMID- 16905750
TI  - Age-related differences in renal function at onset of renal replacement therapy
      in chronic kidney disease stage 5 patients.
AB  - BACKGROUND: Guidelines for initiating renal replacement therapy (RRT) are based
      on renal function and not age, so renal function at onset of RRT is expected to
      be similar across age groups. AIM: To evaluate renal function at initiation of
      RRT across age groups. DESIGN: Observational cross-sectional study. METHODS: We
      extracted data for all incident chronic kidney disease (CKD) stage 5 patients (n
      = 322 064) commenced on chronic dialysis (haemodialysis and peritoneal) and renal
      transplant in the US from 1995 to 1999 from the US Renal Data Systems (USRDS).
      Subjects (n = 662) with incomplete data were excluded. The reminder (n = 321 402)
      were classified into five age groups: 0-19 years; 20-44 years; 45-64 years; 65-74
      years; >/=75 years. Mean values of serum creatinine (Cr, mg/dl), creatinine
      clearance (CrCl, ml/min), body weight (kg) and body mass index (BMI, kg/m(2)) at
      onset of RRT were computed. Mean daily urinary creatinine excretion per kg body
      weight (CrCl x Cr/0.07/weight) was also calculated. RESULTS: Progressively lower
      serum creatinine levels were found in adult patients with increasing age (10.70,
      8.56, 7.38 and 6.88 mg/dl in those aged 20-44 years, 45-64 years, 65-74 years,
      >/=75 years, respectively). CrCl was also lower in the same groups (14.76, 13.38,
      11.63 and 11.60 ml/min, respectively). DISCUSSION: Older patients have a greater
      reduction in renal function than younger patients at onset of RRT, suggesting a
      delay in initiation of therapy.

PMID- 16905751
TI  - Early neurological deterioration in acute stroke: clinical characteristics and
      impact on outcome.
AB  - BACKGROUND: A significant proportion of acute stroke patients suffer neurological
      deterioration during the first few days of recovery. AIM: To explore the
      frequency, clinical characteristics, and consequences of early neurological
      deterioration during the acute recovery period. METHODS: We assessed all
      consecutive patients admitted to a University hospital with suspected stroke. We
      recorded the following on admission: baseline characteristics, physiological
      parameters and laboratory results. On day 5 we recorded occurrence of
      complications, and functional outcome. Early neurological deterioration was
      defined as an increase in National Institute of Health Stroke Score (NIHSS) by
      two or more points (or stroke-related death) between admission and day 5.
      RESULTS: We recruited 188 stroke patients, of whom 36 (19%) suffered early
      neurological deterioration. Patients with early neurological deterioration were
      significantly more likely to: (i) arrive at the hospital earlier (median 2.25 vs.
      7.2 h, p = 0.015); (ii) have a history of atrial fibrillation (33% vs. 16%, p =
      0.039); (iii) be current non-smokers (24% vs. 11%, p = 0.041); (iv) have a severe
      stroke-more total anterior circulation strokes (67% vs. 26%, p < 0.001) and worse
      NIHSS and GCS scores; (v) have intracerebral haemorrhage (22% vs. 7%, p = 0.011);
      (vi) have higher serum urea (mean 7.8 vs. 6.5 mmol/l, p = 0.035) and leukocyte
      count (mean 12.6 vs. 9.7 x 10(9)/l, p = 0.044); and (vi) die in hospital (44% vs.
      10%, OR 12.8, 95%CI 3.8-43.1, p < 0.001). DISCUSSION: Early neurological
      deterioration is a frequent and important complication in acute stroke, with a
      poor short-term prognosis. Effective treatment strategies are urgently needed to
      reduce its occurrence and impact on recovery.

PMID- 16905752
TI  - Primary Whipple's disease of the brain: characterization of the clinical syndrome
      and molecular diagnosis.
AB  - BACKGROUND: Whipple's disease (WD) of the brain without evidence of systemic
      involvement is a rare illness that is difficult to recognize and potentially life
      threatening. AIM: To elucidate the clinical features and diagnosis of primary WD
      of the brain. DESIGN: A single case study, with review of published data.
      METHODS: We linked the information about our patient with 956 citations to
      published WD material. We were able to identify 19 other patients with primary WD
      of the brain. RESULTS: Our patient was a 48-year-old woman who presented 2 years
      ago with generalized tonic/clonic seizures. WD of the brain was diagnosed after a
      life-threatening subacute deterioration leading to reduced consciousness and eye
      movement abnormalities. She had atrophy and gliosis of the right hippocampal
      formation, and nodular enhanc-ing lesions. She developed the syndrome of
      inappropriate ADH secretion, blepharospasm with a complete paralysis of vertical
      gaze, a severe amnesic syndrome, obstructive sleep apnoea, altered sleep
      physiology and CSF oligoclonal bands. Primary WD of the brain was diagnosed after
      PCR confirmed Tropheryma whipplei DNA in CSF and blood. She recovered after
      intravenous methylprednisolone, meropenem and cotrimoxazole. She has now survived
      for 24 months, lives independently and drives. Comparing our patient with the 19
      others, two clinical syndromes were apparent, in both adults and children: (i)
      multifarious neurological symptoms and signs with a CT or MRI showing multiple
      nodular enhancing lesions; (ii) focal neurology secondary to solitary mass
      lesions. DISCUSSION: Primary WD of the brain may be diagnosed by recognition of
      these two clinical syndromes, and confirmed by the application of molecular
      biological techniques such as PCR.

PMID- 16905753
TI  - Short-lasting unilateral neuralgiform headache attacks with conjunctival
      injection and tearing (SUNCT) or cranial autonomic features (SUNA)--a prospective
      clinical study of SUNCT and SUNA.
AB  - Short-lasting unilateral neuralgiform headache attacks with conjunctival
      injection and tearing (SUNCT) and short-lasting unilateral neuralgiform headache
      attacks with cranial autonomic features (SUNA) are described, although SUNA is
      rarely reported. The phenotype of SUNCT and SUNA was characterized from a large
      series of patients (43 SUNCT, 9 SUNA). Three attack types were identified: stabs,
      groups of stabs and saw-tooth attacks. The mean duration of stabs was 58 s (1-600
      s); stab groups, 396 s (10-1200 s); and saw-tooth, 1160 s (5-12 000s). The attack
      frequency was a mean of 59 attacks/day (2-600), and this depended largely on the
      type of attack. The pain was orbital, supraorbital or temporal in 38 (88%) SUNCT
      and 7 (78%) SUNA, and also occurred in the retro-orbital region, side, top, back
      of head, second and third trigeminal divisions, teeth, neck and ear. All SUNCT
      patients had conjunctival injection and tearing. Two SUNA patients had
      conjunctival injection, four had tearing, but none had both. Other cranial
      autonomic symptoms included nasal blockage, rhinorrhoea, eyelid oedema, facial
      sweating/flushing and ear flushing. Cutaneous stimuli triggered attacks in 74% of
      SUNCT but only in 22% of SUNA patients. The majority (95% SUNCT and 89% SUNA) had
      no refractory period between attacks. For SUNCT 58% and for SUNA 56% of patients
      were agitated with the attacks. We propose a new set of diagnostic criteria for
      these syndromes to better encompass the clinical presentations and which include
      a wider range of attack length, wider trigeminal pain distribution, cutaneous
      triggering and lack of refractory period.

PMID- 16905754
TI  - Postoperative radiotherapy for patients with prostate cancer in Japan; Changing
      trends in national practice between 1996-98 and 1999-2001: Patterns of care study
      for prostate cancer.
AB  - OBJECTIVE: To evaluate the changing trends of standards and practices for
      postoperative radiotherapy (RT) for patients with prostate cancer in Japan.
      METHODS: The Japanese Patterns of Care Study (PCS) conducted a national survey in
      84 institutions from 1996 to 1998 (PCS96-98) and 76 institutions from 1999 to
      2001 (PCS99-01). Detailed information relevant to RT was collected on a total of
      169 patients (64 from 1996 to 1998 and 105 from 1999 to 2001) with prostate
      cancer who had undergone radical prostatectomy. RESULTS: The fraction of clinical
      T3-4 tumours before prostatectomy decreased from 63% in the period 1996-98 to 26%
      in the period 1999-2001 (P = 0.0004). The pre-RT prostate-specific antigen level
      was significantly lower in 1999-2001 than in 1996-98 (P = 0.0002). We did not
      find a significant difference in the percentage of patients who received pelvic
      irradiation in the time periods between PCS96-98 and PCS99-01 (P = 0.18).
      Although the median radiation doses of 60 Gy were not changed between the
      surveys, various doses (from 20 to 74.6 Gy) were delivered to the prostatic bed.
      In the 1999-2001 survey, 73 of 105 patients received a median dose of 56 Gy in an
      adjuvant setting, while the other 32 received a median dose of 60 Gy in a salvage
      setting (P = 0.0015). CONCLUSION: These data suggest that consensus has not been
      reached on the practice and management of postoperative RT for patients with
      prostate cancer in Japan.

PMID- 16905756
TI  - Efficacy and feasibility of cisplatin-based concurrent chemoradiotherapy for
      nasopharyngeal carcinoma.
AB  - OBJECTIVE: To investigate the efficacy and feasibility of a cisplatin-based
      concurrent chemoradiotherapy (CRT) protocol based on Intergroup Study 0099 for
      nasopharyngeal carcinoma (NPC). METHODS: Sixteen patients with stage II-IVB NPC
      were treated with a protocol of cisplatin-based concurrent CRT and adjuvant
      chemotherapy from 1998 to 2002. Three courses of cisplatin (80 mg/m2) were
      scheduled during 70 Gy of radiotherapy (RT), and two agents of adjuvant
      chemotherapy (FP regimen: cisplatin 80 mg/m2 and 5-fluorouracil 800 mg/m2/day by
      4-day continuous infusion) were challenged. Overall survival (OS) and relapse
      free survival (RFS) rates were calculated by the Kaplan-Meier method. RESULTS:
      Median follow-up duration was 45 months. Both 3-year OS and RFS rates were 81%.
      Proportions of patients who tolerated each scheduled treatment were 94% for RT,
      63% for concurrent chemotherapy and 38% for adjuvant chemotherapy. CONCLUSIONS:
      Our protocol of the cisplatin-based concurrent CRT followed by adjuvant
      chemotherapy consisting of FP regimen was effective for Japanese patients with
      NPC. However, the doses and numbers of cycle of chemotherapy need to be modified
      because of the low compliance rate. Larger numbers of data accumulation and/or
      multi-institutional trials may be warranted to confirm the efficacy of this
      protocol.

PMID- 16905755
TI  - Analysis of prognostic variables among patients with locally advanced head and
      neck cancer treated with late chemo-intensification protocol: impact of nodal
      density and total tumor volume.
AB  - OBJECTIVE: The aim of the present study was to define the prognostic impact of
      nodal density (ND) and total tumor volume along with many other tumor, treatment
      and patient related variables using the late chemo-intensification treatment
      regimen with conventionally fractionated radiotherapy (70 Gy/7 weeks). METHODS: A
      total of 74 patients with Stage III and IV biopsy proven squamous cell carcinoma
      of oropharynx, hypopharynx and larynx were treated with this regimen. ND and
      total tumor volume was measured on high resolution CT scans for all the patients.
      Chemotherapy consisted of continuous infusion of 5 FU at 350 mg/m(2)/day and
      cisplatin as 1 h infusion at 10 mg/m(2)/day on days 1-5 of week 6 and 7 of
      radiotherapy. RESULTS: Grade III mucositis was present in 48 (64.9%) patients.
      Overall complete response rate was 77%. At 28 months, locoregional relapse-free
      survival (LRFS), overall survival (OS) and distant metastases-free survival
      (DMFS) was 70.8%, 66.9% and 81.9%, respectively. In the final multivariate Cox
      regression model tumor stage, ND, primary site and nodal stage were independent
      variables predicting for LRFS. Similarly AJCC group staging, ND and total
      treatment volume were found to have significant impact, independently over LRFS.
      CONCLUSIONS: There is tremendous variation in terms of ND and total tumor volume
      within AJCC nodal staging and tumor staging, respectively. ND had significant
      impact over LRFS and OS. Future phase III trial may need stratification on the
      basis of these variables.

PMID- 16905757
TI  - Isolated pancreatic metastasis of extremity myxoid liposarcoma: Report of a case.
AB  - Myxoid liposarcoma (ML) has a high predilection for extrapulmonary sites of
      metastases, including intra-abdominal metastases, but pancreatic involvement is
      extremely rare. Here, we report the case of a 66-year-old male patient, who
      underwent pancreaticoduodenectomy for isolated pancreatic metastasis of ML of the
      left lower extremity that had been excised 6 years before. Completion
      pancreatectomy was necessitated afterwards for a delayed haemorrage associated
      with pancreatic fistula. Currently the patient is alive with no evidence of
      disease. Highly selected patients with isolated pancreatic metastasis of soft
      tissue sarcoma may benefit from a curative surgical resection.

PMID- 16905759
TI  - Dose-area product measurements in panoramic dental radiology.
AB  - In this study, dose-area product (DAP) measurements in panoramic dental radiology
      have been performed in Germany. The results obtained in this study were proposed
      as diagnostic reference levels (DRLs). A representative number of dental
      panoramic units, both with digital and conventional image receptors, have been
      chosen. Common statistical parameters such as mean, standard deviation and 3rd
      quartile have been calculated. For four different standard programmes, 'large
      adult', 'adult male', 'adult female' and 'child', the proposed DRLs are 101, 87,
      84 and 75 mGy cm(2), respectively. No clear tendency to a generalised dose
      reduction from the transition to digital techniques has been observed. Effective
      doses have been calculated from E/DAP conversion factors published in literature.
      Even though these values differ by a factor of approximately 3, upper limits of
      15.8-21.2 microSv for the four different exposure settings were derived from the
      data.

PMID- 16905758
TI  - Room model with three modal distributions of attached 220Rn progeny and dose
      conversion factor.
AB  - Jacobi parametric room model was extended to the three modal distribution of
      aerosols, and applied to (220)Rn progeny. The computer program was developed to
      calculate ratios of progeny activity concentrations in different modes to (220)Rn
      concentration. The ratios are relatively small and they are given as functions on
      ventilation rate. Dose conversion factor (DCF) for (220)Rn progeny was calculated
      as 4.5 mSv WLM(-1), which is smaller by over three times than that for (222)Rn
      progeny.

PMID- 16905760
TI  - Japanese adult male voxel phantom constructed on the basis of CT images.
AB  - A Japanese adult male voxel (volume pixel) phantom (hereinafter referred to as
      the JM phantom) was constructed on the basis of CT images of a healthy Japanese
      adult male volunteer. Body characteristics of the JM phantom were compared with
      those of a voxelised MIRD5 type phantom and a Japanese adult male voxel phantom
      which was previously developed. The voxel size of the JM phantom is 0.98 x 0.98 x
      1 mm(3). The shapes of the organs of the JM phantom, even for small or
      complicated organs, such as thyroid and stomach, are more realistically
      reproduced as compared with the previous Japanese voxel phantom (voxel size: 0.98
      x 0.98 x 10 mm(3)). Photon self-absorbed fractions (self-AFs) for brain, kidneys,
      spleen, pancreas, thyroid and urinary bladder wall of JM were evaluated and were
      compared with those of the other phantoms. In consequence, it was suggested that
      the mass, shape and thickness of organs are important factors for the
      determination of self-AFs.

PMID- 16905761
TI  - Consideration on calibration and correction factors of an Hp10 chamber for
      different radiation qualities and angles of incidence.
AB  - This paper presents the characterisation performed at IRSN (France) of an
      H(p)(10) chamber in terms of calibration coefficient and correction factors for
      the radiation qualities of ISO narrow spectrum series. The chamber response,
      expressed in H(p)(10) using conversion coefficients h(p)(K)(10; N, alpha) listed
      in ISO 4037-3 in the energy range from 30 to 1250 keV and for angles of incidence
      between 0 and 70 degrees, was found to be within approximately 10%. However, for
      photon energies <30 keV, an overresponse of the chamber that could reach 100% was
      observed. Nevertheless, this overresponse was reduced to 25% using the conversion
      coefficients estimated at Physikalisch-Technische Bundesanstalt (PTB). This
      implies that the X-ray spectra produced by the IRSN X-ray units are very similar
      to those produced by PTB, both containing a little bit more high-energy photons
      than the spectra used in ISO 4037-3. The dose rate dependence of the chamber
      tested by gamma radiation from (60)Co sources was found to be within 2% in the
      range of 0.3 mSv h(-1) to 1 Sv h(-1). The H(p)(10) chamber can measure directly
      the conventional true value of H(p)(10) after calibration by a reference
      laboratory, and can be used for transferring H(p)(10) reference quantities from a
      reference laboratory.

PMID- 16905762
TI  - Preparation and investigation of thermoluminescence properties of CaSO4:Tm,Cu.
AB  - A new sort of thermoluminescent phosphor has been developed with the purpose of
      enlarging the range of linear dose-response. The thermoluminescence properties of
      CaSO(4):Tm,Cu, prepared according to our method, were studied in the dose range
      of 0.5 Gy-125.0 kGy. The results of the present work show that the CaSO(4):Tm,Cu
      is an excellent new dosimetric material due to its relatively simple glow curve,
      as a consequence of its simple trap system. Several applications are possible in
      dosimetry due to its wide range of linearity (2 x 10(-6) to 2 x 10(3) Gy), from
      environmental and space dosimetry to accidental and high-dose irradiation, e.g.
      gamma irradiation facilities, electron accelerators, nuclear power plants,
      radiotherapy, medical physics, and so on.

PMID- 16905764
TI  - Clinical medication review by a pharmacist of elderly people living in care homes
      -randomised controlled trial.
AB  - OBJECTIVE: to measure the impact of pharmacist-conducted clinical medication
      review with elderly care home residents. DESIGN: randomised controlled trial of
      clinical medication review by a pharmacist against usual care. SETTING: sixty
      five care homes for the elderly in Leeds, UK. PARTICIPANTS: a total of 661
      residents aged 65+ years on one or more medicines. INTERVENTION: clinical
      medication review by a pharmacist with patient and clinical records.
      Recommendations to general practitioner for approval and implementation. Control
      patients received usual general practitioner care. MAIN OUTCOME MEASURES:
      primary: number of changes in medication per participant. Secondary: number and
      cost of repeat medicines per participant; medication review rate; mortality,
      falls, hospital admissions, general practitioner consultations, Barthel index,
      Standardised Mini-Mental State Examination (SMMSE). RESULTS: the pharmacist
      reviewed 315/331 (95.2%) patients in 6 months. A total of 62/330 (18.8%) control
      patients were reviewed by their general practitioner. The mean number of drug
      changes per patient were 3.1 for intervention and 2.4 for control group (P <
      0.0001). There were respectively 0.8 and 1.3 falls per patient (P < 0.0001).
      There was no significant difference for GP consultations per patient (means 2.9
      and 2.8 in 6 months, P = 0.5), hospitalisations (means 0.2 and 0.3, P = 0.11),
      deaths (51/331 and 48/330, P = 0.81), Barthel score (9.8 and 9.3, P = 0.06),
      SMMSE score (13.9 and 13.8, P = 0.62), number and cost of drugs per patient (6.7
      and 6.9, P = 0.5) (pounds sterling 42.24 and pounds sterling 42.94 per 28 days).
      A total of 75.6% (565/747) of pharmacist recommendations were accepted by the
      general practitioner; and 76.6% (433/565) of accepted recommendations were
      implemented. CONCLUSIONS: general practitioners do not review most care home
      patients' medication. A clinical pharmacist can review them and make
      recommendations that are usually accepted. This leads to substantial change in
      patients' medication regimens without change in drug costs. There is a reduction
      in the number of falls. There is no significant change in consultations,
      hospitalisation, mortality, SMMSE or Barthel scores.

PMID- 16905766
TI  - Investigation and treatment of repeated implantation failure following IVF-ET.
AB  - Pregnancy rate following one cycle of IVF and ET can be as high as 60%. But even
      in the very successful units, some couples fail repeatedly. The causes for
      repeated implantation failure (RIF) may be because of reduced endometrial
      receptivity, embryonic defects or multifactorial causes. Various uterine
      pathologies, such as thin endometrium, altered expression of adhesive molecules
      and immunological factors, may decrease endometrial receptivity, whereas genetic
      abnormalities of the male or female, sperm defects, embryonic aneuploidy or zona
      hardening are among the embryonic reasons for failure of implantation.
      Endometriosis and hydrosalpinges may adversely influence both. In this mini
      review, we discuss the suggested methods for evaluation and treatment of RIF:
      repeated hysteroscopy, myomectomy, endometrial stimulation, immunotherapy,
      preimplantation genetic screening (PGS), assisted hatching, zygote intra
      Fallopian transfer (ZIFT), co-culture, blastocyst transfer, cytoplasmic transfer,
      tailoring stimulation protocols and salpingectomy for hydrosalpinges.

PMID- 16905767
TI  - 1,2-propanediol and the type of cryopreservation procedure adversely affect mouse
      oocyte physiology.
AB  - BACKGROUND: The aim of this work was to examine the effect of 1,2-propanediol
      (PrOH) and type of cryopreservation procedure (slow freezing and vitrification)
      on oocyte physiology. METHODS: Intracellular calcium of mouse metaphase II (MII)
      oocytes was quantified by fluorescence microscopy. The effect of PrOH on cell
      physiology was further assessed through analysis of zona pellucida hardening and
      cellular integrity. Protein profiles of cryopreserved oocytes were generated by
      time-of-flight mass spectrometry (TOF-MS). RESULTS: PrOH caused a protracted
      increase in calcium, which was sufficient to induce zona pellucida hardening and
      cellular degeneration. Using 'nominally calcium free' media during PrOH exposure
      significantly reduced the detrimental effects. Proteomic analysis identified
      numerous up- and down-regulated proteins after slow freezing when compared with
      control and vitrified oocytes. CONCLUSIONS: Using such approaches to assess
      effects on cellular physiology is fundamental to improving assisted reproduction
      techniques (ART). This study demonstrates that PrOH causes a significant rise in
      intracellular calcium. Using calcium-free media significantly reduced the
      increase in calcium and the associated detrimental physiological effects,
      suggesting that calcium-free media should be used with PrOH. In addition,
      analysis of the oocyte proteome following cryopreservation revealed that slow
      freezing has a significant effect on protein expression. In contrast,
      vitrification had a minimal impact, indicating that it has a fundamental
      advantage for the cryopreservation of oocytes.

PMID- 16905765
TI  - Seminal plasma and prostaglandin E2 up-regulate fibroblast growth factor 2
      expression in endometrial adenocarcinoma cells via E-series prostanoid-2 receptor
      mediated transactivation of the epidermal growth factor receptor and
      extracellular signal-regulated kinase pathway.
AB  - BACKGROUND: Prostaglandin E(2) (PGE(2)) has been shown to modulate angiogenesis
      and tumour progression via the E-series prostanoid-2 (EP2) receptor. Endometrial
      adenocarcinomas may be exposed to endogenous PGE(2) and exogenous PGE(2), present
      at high concentration in seminal plasma. METHODS: This study investigated
      fibroblast growth factor 2 (FGF2) mRNA expression and cell signalling in response
      to seminal plasma or PGE(2), using an endometrial adenocarcinoma (Ishikawa) cell
      line stably expressing the EP2 receptor (EP2 sense cells) and endometrial
      adenocarcinoma explants. RESULTS: Seminal plasma and PGE(2) induced a significant
      up-regulation of FGF2 expression in EP2 sense but not parental untransfected
      Ishikawa (wild-type) cells (P < 0.05). These effects were inhibited by co
      treatment with EP2 receptor antagonist or inhibitors of protein kinase A, c-Src,
      epidermal growth factor receptor (EGFR) kinase or extracellular signal-regulated
      kinase (ERK) signalling. The treatment of EP2 sense cells with seminal plasma
      induced cAMP accumulation and phosphorylation of c-Src, EGFR kinase and ERK via
      the EP2 receptor. Finally, seminal plasma and PGE(2) significantly increased FGF2
      mRNA expression in endometrial adenocarcinoma tissue explants via the EP2
      receptor (P < 0.05). CONCLUSIONS: Seminal plasma and PGE(2) can similarly
      activate FGF2 expression and EP2 receptor signalling in endometrial
      adenocarcinoma cells. These data highlight the potential for seminal plasma
      exposure to facilitate tumorigenesis-angiogenesis in endometrial adenocarcinomas
      in vivo.

PMID- 16905768
TI  - Decrease in intramuscular lipid droplets and translocation of HSL in response to
      muscle contraction and epinephrine.
AB  - A better understanding of skeletal muscle lipid metabolism is needed to identify
      the molecular mechanisms relating intramuscular triglyceride (IMTG) to muscle
      metabolism and insulin sensitivity. An increasing number of proteins have been
      reported to be associated with intracellular triglyceride (TG), among them the
      PAT family members: perilipin, ADRP (for adipocyte differentiation-related
      protein), and TIP47 (for tail-interacting protein of 47 kDa). Hormone-sensitive
      lipase (HSL) is thought to be the major enzyme responsible for IMTG hydrolysis in
      skeletal muscle. In adipocytes, regulation of HSL by intracellular redistribution
      has been demonstrated. The existence of such regulatory mechanisms in skeletal
      muscle has long been hypothesized but has never been demonstrated. The aim of
      this study was to characterize the PAT family proteins associated with IMTG and
      to investigate the effect of epinephrine stimulation or muscle contraction on
      skeletal muscle TG content and HSL intracellular distribution. Rat soleus muscles
      were either incubated with epinephrine or electrically stimulated for 15 min.
      Single muscle fibers were used for morphological analysis by confocal and
      transmission electron microscopy. We show a decrease in IMTG in response to both
      lipolytic stimuli. Furthermore, we identify two PAT family proteins, ADRP and
      TIP47, associated with IMTG. Finally, we demonstrate HSL translocation to IMTG
      and ADRP after stimulation with epinephrine or contraction.

PMID- 16905769
TI  - Hdmx modulates the outcome of p53 activation in human tumor cells.
AB  - Tumors that express wild-type P53 provide a target for therapies designed to
      reactivate P53 function. This is supported by the potent activation of P53 in
      tumor cells by Nutlin, a cis-imidazoline that inhibits the Hdm2-P53 interaction.
      The efficacy of Hdm2.P53 antagonists could be compromised if they do not
      antagonize Hdmx, an Hdm2 homolog that inhibits P53 transactivation. We evaluated
      the role of Hdmx expression in sensitivity to Nutlin in a range of cancer cell
      lines. Nutlin reduced Hdmx levels in normal cells and some cancer cell lines,
      whereas other cancer cells were refractory to such down-regulation. Strikingly,
      Nutlin did not disrupt Hdmx.P53 complexes, and in cell lines where no Hdmx
      degradation occurred, Nutlin failed to induce apoptosis. shRNA-mediated reduction
      of Hdmx sensitized cells to apoptosis, but caspase-3 was neither required nor
      sufficient for Hdmx degradation or apoptosis. Our data imply that Hdmx is an
      important determinant of the outcome of P53 activation. Thus, targeting Hdmx may
      be a therapeutic strategy that complements drugs such as Nutlin.

PMID- 16905770
TI  - Structures of R- and T-state Escherichia coli aspartokinase III. Mechanisms of
      the allosteric transition and inhibition by lysine.
AB  - Aspartokinase III (AKIII) from Escherichia coli catalyzes an initial commitment
      step of the aspartate pathway, giving biosynthesis of certain amino acids
      including lysine. We report crystal structures of AKIII in the inactive T-state
      with bound feedback allosteric inhibitor lysine and in the R-state with aspartate
      and ADP. The structures reveal an unusual configuration for the regulatory ACT
      domains, in which ACT2 is inserted into ACT1 rather than the expected tandem
      repeat. Comparison of R- and T-state AKIII indicates that binding of lysine to
      the regulatory ACT1 domain in R-state AKIII instigates a series of changes that
      release a "latch", the beta15-alphaK loop, from the catalytic domain, which in
      turn undergoes large rotational rearrangements, promoting tetramer formation and
      completion of the transition to the T-state. Lysine-induced allosteric transition
      in AKIII involves both destabilizing the R-state and stabilizing the T-state
      tetramer. Rearrangement of the catalytic domain blocks the ATP-binding site,
      which is therefore the structural basis for allosteric inhibition of AKIII by
      lysine.

PMID- 16905771
TI  - Crn7 interacts with AP-1 and is required for the maintenance of Golgi morphology
      and protein export from the Golgi.
AB  - Crn7 is a novel cytosolic mammalian WD-repeat protein of unknown function that
      associates with Golgi membranes. Here, we demonstrate that Crn7 knockdown by
      small interfering RNA results in dramatic changes in the Golgi morphology and
      function. First, the Golgi ribbon is disorganized in Crn7 KD cells. Second, the
      Golgi export of several marker proteins including VSV envelope G glycoprotein is
      greatly reduced but not the retrograde protein import into the Golgi complex. We
      further establish that Crn7 co-precipitates with clathrin adaptor AP-1 but is not
      required for AP-1 targeting to Golgi membranes. We identify tyrosine 288-based
      motif as part of a canonical YXXPhi sorting signal and a major mu1-adaptin
      binding site in vitro. This study provides the first insight into the function of
      mammalian Crn7 protein in the Golgi complex.

PMID- 16905772
TI  - Apo- and holo-structures of 3alpha-hydroxysteroid dehydrogenase from Pseudomonas
      sp. B-0831. Loop-helix transition induced by coenzyme binding.
AB  - Bacterial 3alpha-hydroxysteroid dehydrogenase, which belongs to a short-chain
      dehydrogenase/reductase family and forms a dimer composed of two 26-kDa subunits,
      catalyzes the oxidoreduction of hydroxysteroids in a coenzyme-dependent manner.
      This enzyme also catalyzes the oxidoreduction of nonsteroid compounds that play
      an important role in xenobiotic metabolism of bacteria. We performed an x-ray
      analysis on the crystal of Ps3alphaHSD, the enzyme from Pseudomonas sp. B-0831
      complexed with NADH. The resulting crystal structure at 1.8A resolution showed
      that Ps3alphaHSD exists as a structural heterodimer composed of apo- and holo
      subunits. A distinct structural difference between them was found in the 185-207
      amino acid region, where the structure in the apo-subunit is disordered whereas
      that in the holo-subunit consists of two alpha-helices. This fact proved that the
      NADH binding allows the helical structures to form the substrate binding pocket
      even in the absence of the substrate, although the region corresponds to the so
      called "substrate-binding loop." The induction of alpha-helices in solution by
      the coenzyme binding was also confirmed by the CD experiment. In addition, the CD
      experiment revealed that the helix-inducing ability of NADH is stronger than that
      of NAD. We discuss the negative cooperativity for the coenzyme binding, which is
      caused by the effect of the structural change transferred between the subunits of
      the heterodimer.

PMID- 16905774
TI  - A piece of my mind. Knowing Ron.

PMID- 16905775
TI  - Anti-HIV microbicide efforts press on.

PMID- 16905776
TI  - Routine male circumcision could prevent millions of HIV infections in Africa.

PMID- 16905777
TI  - HIV vaccine research gets 287 million dollars boost.

PMID- 16905778
TI  - Mentoring program supports new generation of HIV researchers.

PMID- 16905779
TI  - Mediators of the association between mortality risk and socioeconomic status.

PMID- 16905780
TI  - Mediators of the association between mortality risk and socioeconomic status.

PMID- 16905781
TI  - Coffee, myocardial infarction, and CYP nomenclature.

PMID- 16905782
TI  - A novel pattern of lipoaccumulation in HIV-infected men.

PMID- 16905784
TI  - Rapid scale-up of antiretroviral therapy at primary care sites in Zambia:
      feasibility and early outcomes.
AB  - CONTEXT: The Zambian Ministry of Health has scaled-up human immunodeficiency
      virus/acquired immunodeficiency syndrome (HIV/AIDS) care and treatment services
      at primary care clinics in Lusaka, using predominately nonphysician clinicians.
      OBJECTIVE: To report on the feasibility and early outcomes of the program.
      DESIGN, SETTING, AND PATIENTS: Open cohort evaluation of antiretroviral-naive
      adults treated at 18 primary care facilities between April 26, 2004, and November
      5, 2005. Data were entered in real time into an electronic patient tracking
      system. INTERVENTION: Those meeting criteria for antiretroviral therapy (ART)
      received drugs according to Zambian national guidelines. MAIN OUTCOME MEASURES:
      Survival, regimen failure rates, and CD4 cell response. RESULTS: We enrolled
      21,755 adults into HIV care, and 16,198 (75%) started ART. Among those starting
      ART, 9864 (61%) were women. Of 15,866 patients with documented World Health
      Organization (WHO) staging, 11,573 (73%) were stage III or IV, and the mean (SD)
      entry CD4 cell count among the 15,336 patients with a baseline result was
      143/microL (123/microL). Of 1142 patients receiving ART who died, 1120 had a
      reliable date of death. Of these patients, 792 (71%) died within 90 days of
      starting therapy (early mortality rate: 26 per 100 patient-years), and 328 (29%)
      died after 90 days (post-90-day mortality rate: 5.0 per 100 patient-years). In
      multivariable analysis, mortality was strongly associated with CD4 cell count
      between 50/microL and 199/microL (adjusted hazard ratio [AHR], 1.4; 95%
      confidence interval [CI], 1.0-2.0), CD4 cell count less than 50/microL (AHR, 2.2;
      95% CI, 1.5-3.1), WHO stage III disease (AHR, 1.8; 95% CI, 1.3-2.4), WHO stage IV
      disease (AHR, 2.9; 95% CI, 2.0-4.3), low body mass index (<16; AHR,2.4; 95% CI,
      1.8-3.2), severe anemia (<8.0 g/dL; AHR, 3.1; 95% CI, 2.3-4.0), and poor
      adherence to therapy (AHR, 2.9; 95% CI, 2.2-3.9). Of 11,714 patients at risk, 861
      failed therapy by clinical criteria (rate, 13 per 100 patient-years). The mean
      (SD) CD4 cell count increase was 175/microL (174/microL) in 1361 of 1519 patients
      (90%) receiving treatment long enough to have a 12-month repeat. CONCLUSION:
      Massive scale-up of HIV and AIDS treatment services with good clinical outcomes
      is feasible in primary care settings in sub-Saharan Africa. Most mortality occurs
      early, suggesting that earlier diagnosis and treatment may improve outcomes.

PMID- 16905783
TI  - Three- vs four-drug antiretroviral regimens for the initial treatment of HIV-1
      infection: a randomized controlled trial.
AB  - CONTEXT: Three-drug antiretroviral regimens are standard of care for initial
      treatment of human immunodeficiency virus 1 (HIV-1) infection, but a 4-drug
      regimen could improve antiretroviral activity and be more effective than a 3-drug
      regimen. OBJECTIVE: To compare the safety/efficacy of 3-drug vs 4-drug regimens
      for initial treatment of HIV-1 infection. DESIGN: The AIDS Clinical Trials Group
      (ACTG) A5095 study, a randomized, double-blind, placebo-controlled study with
      enrollment and follow-up conducted from March 22, 2001, to March 1, 2005, and
      enrolling treatment-naive, HIV-1-infected patients with HIV-1 RNA levels of 400
      copies/mL or greater from US clinical trials units of the ACTG. INTERVENTIONS:
      Zidovudine/lamivudine plus efavirenz (3-drug regimen) vs
      zidovudine/lamivudine/abacavir plus efavirenz (4-drug regimen). MAIN OUTCOME
      MEASURES: Time to virologic failure (defined as time to first of 2 successive HIV
      1 RNA levels > or =200 copies/mL at or after week 16), CD4 cell count changes,
      and grade 3 or 4 adverse events. HIV-1 RNA data were intent-to-treat, regardless
      of treatment changes. RESULTS: Seven hundred sixty-five patients with a baseline
      mean HIV-1 RNA level of 4.86 log10 (72,444) copies/mL and CD4 cell count of 240
      cells/mm3 were randomized. After a median 3-year follow-up, 99 (26%) of 382 and
      94 (25%) of 383 patients receiving the 3-drug and 4-drug regimens, respectively,
      reached protocol-defined virologic failure; time to virologic failure was not
      significantly different (hazard ratio, 0.95; 97.5% confidence interval, 0.69
      1.33; P = .73). In planned subgroup analyses, increased risk for virologic
      failure was seen in non-Hispanic black patients (adjusted hazard ratio, 1.66; 95%
      confidence interval, 1.18-2.34; P = .003). At 3 years, the HIV-1 RNA level was
      less than 200 copies/mL in 152 (90%) of 169 and 143 (92%) of 156 patients
      receiving the 3-drug and 4-drug regimens, respectively (P = .59), and less than
      50 copies/mL in 144 (85%) of 169 and 137 (88%) of 156 patients (P = .39). CD4
      cell count increases and grade 3 or 4 adverse events were not significantly
      different. CONCLUSIONS: In treatment-naive patients, there were no significant
      differences between the 3-drug and 4-drug antiretroviral regimens; overall, at
      least approximately 80% of patients had HIV-1 RNA levels less than 50 copies/mL
      through 3 years. These results support current guidelines recommending 2
      nucleosides plus efavirenz for initial treatment of HIV-1 infection; adding
      abacavir as a fourth drug provided no additional benefit. CLINICAL TRIALS
      REGISTRATION: clinicaltrials.gov Identifier: NCT00013520.

PMID- 16905785
TI  - Breastfeeding plus infant zidovudine prophylaxis for 6 months vs formula feeding
      plus infant zidovudine for 1 month to reduce mother-to-child HIV transmission in
      Botswana: a randomized trial: the Mashi Study.
AB  - CONTEXT: Postnatal transmission of human immunodeficiency virus-1 (HIV) via
      breastfeeding reverses gains achieved by perinatal antiretroviral interventions.
      OBJECTIVE: To compare the efficacy and safety of 2 infant feeding strategies for
      the prevention of postnatal mother-to-child HIV transmission. DESIGN, SETTING,
      AND PATIENTS: A 2 x 2 factorial randomized clinical trial with peripartum (single
      dose nevirapine vs placebo) and postpartum infant feeding (formula vs
      breastfeeding with infant zidovudine prophylaxis) interventions. In Botswana
      between March 27, 2001, and October 29, 2003, 1200 HIV-positive pregnant women
      were randomized from 4 district hospitals. Infants were evaluated at birth,
      monthly until age 7 months, at age 9 months, then every third month through age
      18 months. INTERVENTION: All of the mothers received zidovudine 300 mg orally
      twice daily from 34 weeks' gestation and during labor. Mothers and infants were
      randomized to receive single-dose nevirapine or placebo. Infants were randomized
      to 6 months of breastfeeding plus prophylactic infant zidovudine (breastfed plus
      zidovudine), or formula feeding plus 1 month of infant zidovudine (formula fed).
      MAIN OUTCOME MEASURES: Primary efficacy (HIV infection by age 7 months and HIV
      free survival by age 18 months) and safety (occurrence of infant adverse events
      by 7 months of age) end points were evaluated in 1179 infants. RESULTS: The 7
      month HIV infection rates were 5.6% (32 infants in the formula-fed group) vs 9.0%
      (51 infants in the breastfed plus zidovudine group) (P = .04; 95% confidence
      interval for difference, -6.4% to -0.4%). Cumulative mortality or HIV infection
      rates at 18 months were 80 infants (13.9%, formula fed) vs 86 infants (15.1%
      breastfed plus zidovudine) (P = .60; 95% confidence interval for difference, 
      5.3% to 2.9%). Cumulative infant mortality at 7 months was significantly higher
      for the formula-fed group than for the breastfed plus zidovudine group (9.3% vs
      4.9%; P = .003), but this difference diminished beyond month 7 such that the time
      to-mortality distributions through age 18 months were not significantly different
      (P = .21). CONCLUSIONS: Breastfeeding with zidovudine prophylaxis was not as
      effective as formula feeding in preventing postnatal HIV transmission, but was
      associated with a lower mortality rate at 7 months. Both strategies had
      comparable HIV-free survival at 18 months. These results demonstrate the risk of
      formula feeding to infants in sub-Saharan Africa, and the need for studies of
      alternative strategies. TRIAL REGISTRATION: clinicaltrials.gov Identifier:
      NCT00197587.

PMID- 16905786
TI  - Regimen simplification to atazanavir-ritonavir alone as maintenance
      antiretroviral therapy after sustained virologic suppression.
AB  - CONTEXT: The long-term adverse effects, expense, and difficulty of adherence to
      antiretroviral regimens have led to studies of simpler maintenance therapies.
      Maintenance therapy with ritonavir-boosted atazanavir alone is a possible option
      because of low pill burden, once-daily dosing, safety, and unique resistance
      profile. OBJECTIVE: To assess whether simplified maintenance therapy with
      atazanavir-ritonavir alone after virologic suppression increases the risk of
      virologic failure (2 consecutive human immunodeficiency virus type 1 [HIV-1] RNA
      measurements of > or =200 copies/mL). DESIGN, SETTING, AND PARTICIPANTS: Single
      group, open-label, multicenter, 24-week pilot study of 36 HIV-infected adults
      with virologic suppression for 48 weeks or longer receiving their first protease
      inhibitor (PI)-based regimen. The study was conducted between September 1, 2004,
      and April 18, 2006, at 12 participating AIDS clinical trial units in the United
      States. INTERVENTION: Participants switched PIs to atazanavir-ritonavir at entry
      and discontinued nucleoside analog reverse transcriptase inhibitors (NRTIs) after
      6 weeks. MAIN OUTCOME MEASURES: Virologic failure within 24 weeks of
      discontinuing NRTIs. Other measures included HIV-1 drug resistance, plasma
      atazanavir concentrations, adverse events, CD4 cell counts, plasma lipid levels,
      and HIV-1 RNA levels in seminal plasma. RESULTS: Thirty-six participants enrolled
      and 2 discontinued before simplification to atazanavir-ritonavir alone. Thirty
      four patients were included in the analysis of the primary end point after 24
      weeks: 1 withdrew voluntarily, and 33 continued the regimen. Virologic success
      (absence of failure) through 24 weeks of simplified therapy occurred in 91% (31
      of 34 patients; lower 90% confidence interval limit = 85%). Three participants
      experienced virologic failure 12, 14, and 20 weeks after simplification, with
      plasma HIV-1 RNA levels of 4730, 1285, and 28 397 copies/mL, respectively.
      Resistance testing at failure did not identify PI resistance mutations. Plasma
      atazanavir concentrations at failure were low or below detection in 2 of 3
      participants experiencing failure. There were no treatment discontinuations for
      adverse events after simplification; no significant changes in CD4 cell counts or
      plasma lipid levels; and no detectable HIV-1 RNA in seminal plasma from all 8
      participants tested. CONCLUSIONS: These preliminary data suggest that simplified
      maintenance therapy with atazanavir-ritonavir alone may be efficacious for
      maintaining virologic suppression in carefully selected patients with HIV
      infection. These findings require confirmation in larger, randomized trials of
      this strategy. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00084019.

PMID- 16905787
TI  - Biology of CCR5 and its role in HIV infection and treatment.
AB  - Chemokine receptors are found on cell surfaces and promote cellular migration by
      chemotaxis. The CC chemokine receptor 5 (CCR5) is used by the human
      immunodeficiency virus (HIV) to infect cells. Strategies that target human CCR5
      are therefore being developed to prevent and treat HIV infection. Antiviral
      strategies that target a host element necessary for viral replication may be
      predicted to interfere with the function of that element and may therefore
      adversely affect the host. We conducted a review of the literature between
      November 2005 and April 2006 with a focus on articles addressing the genetics and
      function of CCR5, the effects of CCR5 deletion in human and murine systems, and
      treatment strategies for HIV infection that target this coreceptor. English
      language articles in the human and murine literature published between March 1996
      and April 2006 were identified through a search of MEDLINE using CCR5 as the
      search term. Relevant articles as judged by their titles and abstracts were
      reviewed in detail. In addition, based on our knowledge of the field and with
      permission, unpublished work was also reviewed. In this article, we explore the
      effects that targeting CCR5 may have on host defenses in individuals with
      immunity already compromised by HIV infection.

PMID- 16905789
TI  - Metabolic and skeletal complications of HIV infection: the price of success.
AB  - Over the past 10 years, in conjunction with the broad availability of potent
      antiretroviral regimens, the care of human immunodeficiency virus (HIV)-infected
      patients has shifted from prevention and treatment of opportunistic infections
      and malignancies to management of the metabolic and related complications
      associated with HIV infection and its treatment. Metabolic disorders, including
      lipodystrophy, dyslipidemia, and insulin resistance, occur at a high rate in HIV
      infected individuals receiving highly active antiretroviral therapy (HAART).
      These disorders are associated with increased risk of cardiovascular disease and
      have become an important cause of morbidity and mortality in HIV-infected
      patients. Herein, we present the case of a patient with HIV infection who
      responded well to HAART but developed multiple complications potentially related
      to this therapy. This article reviews the clinical characteristics of the
      metabolic and skeletal disturbances observed in HIV infection and discusses
      strategies for their management.

PMID- 16905788
TI  - Treatment for adult HIV infection: 2006 recommendations of the International AIDS
      Society-USA panel.
AB  - CONTEXT: Guidelines for antiretroviral therapy are important for clinicians
      worldwide given the complexity of the field and the varied clinical situations in
      which these agents are used. The International AIDS Society-USA panel has updated
      its recommendations as warranted by new developments in the field. OBJECTIVE: To
      provide physicians and other human immunodeficiency virus (HIV) clinicians with
      current recommendations for the use of antiretroviral therapy in HIV-infected
      adults in circumstances for which there is relatively unrestricted access to
      drugs and monitoring tools. The recommendations are centered on 4 key issues:
      when to start antiretroviral therapy; what to start; when to change; and what to
      change. Antiretroviral therapy in special circumstances is also described. DATA
      SOURCES AND STUDY SELECTION: A 16-member noncompensated panel was appointed,
      based on expertise in HIV research and patient care internationally. Data
      published or presented at selected scientific conferences from mid 2004 through
      May 2006 were identified and reviewed by all members of the panel. DATA
      EXTRACTION AND SYNTHESIS: Data that might change previous guidelines were
      identified and reviewed. New guidelines were drafted by a writing committee and
      reviewed by the entire panel. CONCLUSIONS: Antiretroviral therapy in adults
      continues to evolve rapidly, making delivery of state-of-the-art care
      challenging. Initiation of therapy continues to be recommended in all symptomatic
      persons and in asymptomatic persons after the CD4 cell count falls below
      350/microL and before it declines to 200/microL. A nonnucleoside reverse
      transcriptase inhibitor or a protease inhibitor boosted with low-dose ritonavir
      each combined with 2 nucleoside (or nucleotide) reverse transcriptase inhibitors
      is recommended with choice being based on the individual patient profile. Therapy
      should be changed when toxicity or intolerance mandate it or when treatment
      failure is documented. The virologic target for patients with treatment failure
      is now a plasma HIV-1 RNA level below 50 copies/mL. Adherence to antiretroviral
      therapy in the short-term and the long-term is crucial for treatment success and
      must be continually reinforced.

PMID- 16905790
TI  - HIV prevention for a threatened continent: implementing positive prevention in
      Africa.

PMID- 16905791
TI  - Scale-up of voluntary HIV counseling and testing in Kenya.

PMID- 16905792
TI  - Preexposure prophylaxis for HIV: unproven promise and potential pitfalls.

PMID- 16905793
TI  - JAMA patient page. HIV infection: the basics.

PMID- 16905794
TI  - Aspirin prophylaxis and the prevalence of anaemia.
AB  - BACKGROUND: Anaemia and vascular disease are both common amongst the elderly and
      frequently co-exist. Whilst a consensus exists concerning the benefits of low
      dose aspirin in reducing risk from atheromatous disease, nonetheless concerns
      arise in view of its harmful effect on gastric mucosa and its influence upon
      haemostasis, with the possibility of subsequent gastrointestinal bleeding. This
      study examined the relationship between chronic low-dose aspirin therapy and the
      presence of anaemia. SETTING: A cross-sectional study of a representative cohort
      of 464 community-dwelling subjects aged 77 years. METHODS: Subjects underwent
      comprehensive assessment of psychosocial, functional, medical and laboratory
      variables. In accordance with the World Health Organization criteria, anaemia was
      defined as less than 13 g/dl for men and 12 g/dl for women. RESULTS: Chronic low
      dose aspirin use was found amongst 29% of the 227 women and 38% of the 237 males
      (P = 0.026). Aspirin use was significantly associated with hypertension,
      ischaemic heart disease and diabetes mellitus. Anaemia was 42% less common among
      aspirin users, a statistically robust finding (OR 2.44, 95%CI 1.28-4.66)
      according to logistic regression analysis which included the confounding
      variables of gender, education, diabetes, hypertension, heart disease, peptic
      diseases, antipeptic therapy and smoking. Similarly, no association was observed
      between aspirin use and reduced serum iron or iron saturation, reduced mean
      corpuscular haemoglobin or mean corpuscular volume. CONCLUSIONS: Chronic low-dose
      aspirin use amongst an elderly cohort was associated with increased likelihood of
      normal haemoglobin.

PMID- 16905795
TI  - The purple urine bag syndrome.

PMID- 16905796
TI  - Non-invasive ventilation for respiratory failure in elderly patients.

PMID- 16905797
TI  - [Modified chemotherapy regimens in selected testicular cancer patients with good
      prognosis].
AB  - The goal of our study was to assess the feasibility of usage of chemotherapy
      regimens with reduced intensity in subgroups of selected patients with good
      prognosis metastatic nonseminomatous germ cell tumor (NSGCT) of the testis. 18
      patients with low-volume stage II NSGCT who achieved normal tumor marker level
      after the first cycle of cisplatin, etoposide and bleomycin (BEP) chemotherapy
      (group 1) received etoposide and cisplatin (EP) as second and third cycles of
      treatment and 15 testicular cancer patients with serological disease only (group
      2) underwent three cycles of EP chemotherapy. The chemotherapy-related side
      effects observed in these patients were compared with those in control group
      consisting of 93 good-prognosis metastatic patients treated with three standard
      cycles of BEP. All patients from both groups achieved complete response with
      chemotherapy alone (14 group 1 and 15 group 2 patients) or by subsequent
      resection of teratoma or necrosis (4 cases from group 1). No relapse with viable
      malignancy was observed after the treatment. All the patients remained free of
      disease during the median follow-up period of 97 and 48 months for groups 1 and 2
      respectively. Compared to the control group, less number of treatment cycles was
      associated with grade III-IV leucopenia in groups 1 (p=0.07) and 2 (p=0.03).
      Reduced intensity chemotherapy regimens showed efficacy equal to the standard
      treatment and can be considered as less toxic therapeutic options in these
      selected patients.

PMID- 16905798
TI  - [Long-term results of nephron-sparing surgery for small renal tumors with
      elective indications].
AB  - The widespread use of modern radiological techniques substantially changed
      clinical presentation of renal cell carcinoma (RCC) in the recent decades.
      Currently, more than one half of all patients with surgically resectable renal
      tumors are detected incidentally. In this due interest in nephron sparing surgery
      (NSS) for the treatment of small localized tumors has increased. The amount of
      healthy parenchyma that should be removed together with the tumor to minimize the
      risk of local recurrence is an important and controversial issue. In the present
      study we retrospectively studied 44 cases of NSS performed for elective
      indications. A total of 44 patients underwent elective NSS from 1994 to 2001.
      According to the operative techniques the patients were distributed in two
      groups. Group I consisted of 17 patients who underwent "enucleoresection" with a
      small part of normal parenchyma around the excised tumors. The rest 27 patients
      (Group II) underwent NSS by means of enucleation. Mean follow-up was 88.36+/
      24.75 months (range: 49-146 months). The mean tumor size was 37,04+/-4,65 cc
      (range: 25 to 45). There was no perioperative mortality. Hemorrhage was observed
      in 1 patient (5,9%) from Group I. Urinary leakage was observed in 3 (6,8%) cases
      in both groups: two (11,7%) in group I and one (3,7%) in group II. No local
      recurrence was observed during the follow-up period. One patient (2, 8%)
      developed distant metastases and died at 81 month postoperatively. 5-year cancer
      specific survival was 97,6 %. Simple tumor enucleation is a safe and acceptable
      approach for elective NSS. It provides excellent long-term progression-free and
      cancer specific survival rates, and is not associated with an increased risk of
      local recurrence compared with partial nephrectomy.

PMID- 16905799
TI  - [Case of simultaneous operations of aortocoronary shunt and panhysterectomy].
AB  - Simultaneous operations on different organs and cavities, including urgent and
      scheduled operations, always are associated with high risk of operative and
      postoperative periods. The case of simultaneous operation of aortocoronary shunt
      and panhysterectomy is presented in the paper. In the case of our patient despite
      the severe condition: occlusion of left anterior descending coronary artery (rest
      and effort angina) and endometrium malignant tumor worsened by concomitant
      pathologies including bronchial asthma, hypothyreosis, pyelonephritis and
      obesity, the surgical intervention was completed successfully without
      complications at operational and postoperational periods.

PMID- 16905800
TI  - [Treatment of patients with breast cancer during lactation and pregnancy].
AB  - Breast cancer is the most frequent form of malignant tumor detected during
      lactation period and pregnancy. The aim of the research was the examination of
      the efficiency of breast cancer patients' treatment. 17 women diseased with
      breast cancer of the T1-2N0-2M0 stage during lactation and pregnancy period were
      involved in the study. The results of the research have exposed the high
      efficiency of the complex medical care of breast cancer patients at the early
      stages of the disease. At the T1-2N0M0 stage, the showings of 5-year common and
      recurrence-free probability of survival have made 52,9 and 47,0%, at T1-2N1M0
      23,5 and 11,8%, at T1-2N2M0 - 5, 9 and 5, 9%. Common probability of survival in
      the examined group of patients has made 82,4% and recurrence-free probability of
      survival - 64,7% (p<0,1). Lethality index was 17,7% (3 patients).

PMID- 16905801
TI  - [Clinical aspect, diagnostics and treatment of follicular ovarian cysts].
AB  - 48 young women aged 16 to 40 were observed for the menstrual cycle disorders and
      pain of various intensity in the lower abdominal region have been diagnosed for
      having at ovarian follicular cyst. The peculiarities of hormonal secretion in 30
      patients have been studied. Existence of transitory hyperprolactinemia, excessive
      production of the lutheinizing hormone and deficit of progesterone production was
      determined. These factors hamper the folliculorexis and the follicular cyst does
      develop. Thus, in the occurrence of follicular cysts the major role belongs to
      the hypothalamic-pituitary disregulation. Therefore, the suppressive hormonal
      therapy is justified as highly effective. Dynamic ultrasound makes it possible to
      identify the conservative treatment terms and where necessary, timely transfer of
      the patient to the laparoscopic treatment.

PMID- 16905802
TI  - [Antiprogesterone for medical abortion].
AB  - The purpose of the research was to evaluate clinical course and efficiency of the
      method of termination of pregnancy in the first end second trimesters by means of
      antiprogesterone. 384 women aged 15 to 45 in the first end second trimesters of
      pregnancy were investigated. 300 women had an early pregnancy (range=2-7 weeks)
      requesting abortion. All these women first took 600 mg antiprogesterone
      pencroftone ("Pencroft-Fharma", Russia) and 48 hours later - 400 mkg
      prostaglandin misoprostol. 84 patients with gestation period ranged from 14 to 22
      weeks. Their contractility utterly was caused with 400 mg pencroftone and 48
      hours later with 400 mkg prostaglandin misopristol. In the first trimester
      completed abortion was observed in 96,7%, incomplete abortion in 1,7%; missed
      abortion in 2,3% cases, continuing pregnancy in 1 case. In the second trimester
      in the case of therapy with pencroftone and prostaglandin E1 misoprostol the
      clinical effect was observed in 96,4% cases. Antiprogesterone pencroftone is an
      effective for medical abortion during I-II trimesters of pregnancy. It is
      characterized by minimal risk of complications in the course and the post
      abortion period.

PMID- 16905803
TI  - [Pregnancy and iron, ferritin and IL-3 in the blood].
AB  - In Georgia, we were first who tried to study adolescent pregnant women with
      anemia (age group 14-18ys). We studied the reasons which have caused anemia in
      the pregnant women of this age. This gave us the opportunity to chose correct
      methods of treatment and establish that adolescents are at increased risk of
      anemia, especially at younger ages (14-16 years). We have studied 200 pregnant
      women, 100 teenagers (study group) and 100 adult women (control group). In both
      groups we have investigated the level of iron, ferritin, and IL-3 in the blood
      serum. Iron-deficiency anemia was observed in the first trimester of pregnancy in
      35% of pregnant adolescents. Usually the quantity of iron in the body during the
      first trimester is close to norm, but in our case, age and inadequate food intake
      in connection with the desire to be slim, play their role. Other clinical
      manifestations of anemia were not revealed. Iron deficiency anemia found in 22%
      of the adult group. Number of pregnant women with iron-deficiency anemia was
      considerably higher in both groups (adolescents and adults) in the third
      trimester, and quantity of ferritin was at the lower border of the norm. The need
      of iron usually increases up to 3mg/day in the second trimester and 3.5-4mg/day
      in the third trimester. In some women Level of IL-3 in the blood was normal (that
      indicate to the adequate hematopoiesis), serum iron quantity was at the lower
      border of the norm, Ferritin level was increased and clinical- laboratory indices
      revealed presence of infection. In our case the number of such patients was 28%
      among adolescents and 21% among adults. In other cases hematopoiesis was normal
      (IL-3 level was normal) and there were no signs of infectious disease, but
      clinical manifestations of anemia were still present which indicated to the
      presence of physiological anemia due to increased circulatory volume.

PMID- 16905804
TI  - [Influence of prenatal and perinatal risk factors on the outcome of pregnancy].
AB  - During the recent years a great number of negative social-economical problems
      (e.g. emotional stresses during the pregnancy, malnutrition, physical labor,
      etc.) characteristic of the so-called transitional period have been observed. All
      these factors have a negative influence on the course of pregnancy and the fetal
      body mass. The main target of our work was to reveal the impact of social
      economical risk-factors on the gestational age and hindrances for the antenatal
      development. Methodology of our research was prospect-retrospective randomized
      case-control study. In 2001-2004 we followed up 267 (study group) and 260
      (control group) newborns. According to the results received the most significant
      factors influencing the gestational age and weight of newborns are as follows:
      poor financial status, emotional stress, malnutrition, physical hyperactivity,
      bad habits (smoking), incidental home nursing, low education level, other bad
      habits (alcohol, drugs).

PMID- 16905805
TI  - [Prevalence of severe maternal morbidity in Tbilisi].
AB  - Cross-sectional study was performed in all maternity units of Tbilisi, Georgia,
      with delivering 18,554 women between 1 January 2004 and 1 January 2005. There
      were 267 cases of severe obstetric morbidity giving a prevalence of 14,2 per 1000
      deliveries (95% CI 12,6-16,0). During the study there were 3 maternal deaths.
      Disease specific morbidities per 1000 deliveries were: severe pre - eclampsia -
      5,0 (95% CI 4,1-6,2); hysterectomy during 24 hours after delivery - 4,5 (95% CI
      3,6-5,6); hemorrhage - 2,3 (95% CI 1,7-3,1), sepsis 1,3 (95% CI 0,9-2,0);
      eclampsia - 0,74 (95% CI 0,44-1,25); uterine rupture - 0,16 (95% CI 0,05-0,47);
      HELLP-syndrome - 0,11 (95% CI 0,03-0,39). Severe obstetric morbidity and its
      relation to mortality may be more sensitive measures of pregnancy outcome than
      mortality alone and allows for an effective audit system of maternal care.

PMID- 16905806
TI  - [Effect of aerosol therapy with cyclopheron in patients with chronic rhinitis].
AB  - Recently the number of patients with nasal cavity diseases has significantly
      increased mainly due to the chronic rhinitis. Due to the topical nature of the
      problem it is necessary to develop new methods of the treatment of chronic
      rhinitis and to use physiotherapeutic factors which have no side effects of
      chemotherapy. Total of 62 patients were investigated. 34 of these patients had
      chronic catarrhal rhinitis and 24 had chronic allergic rhinitis. It has been
      established that aerosol-therapy with cyclopheron has a considerable effect in
      patients with these forms of chronic rhinitis, right up to full normalization of
      their condition as well as on rhinoscopic data, particularly on the olfactory
      function and mucociliar clearance. Decrease of neutrophiles and eosinophiles
      present in the mucous discharged from the nasal cavity has a bacteriostatic
      action expressing in the decrease of size of colonies of microbial cultures.

PMID- 16905807
TI  - [Comparative analyses of colonization degree of oral cavity by microbial flora
      during application of teeth prosthetic devices].
AB  - The degree of adhesion and colonization was studied among 27 patients with
      generalized paradontitis of moderate severity and in remission stage. All these
      patients had different material teeth prostheses. 12 patients had acrylic plastic
      "Ftorax" material prostheses and 15 of them polypropylenes prostheses. Prostheses
      prepared from acryl plastic were intensively colonized by stable microflora of
      oral cavity, as well as by paradontopathogens, whereas usage of polypropylenes
      prostheses is rather effective for patients with paradontitis, because it is
      followed by partial recovery of stable microflora and lack of secretion of
      parodontopathogenic types, such as actynomycetes, prevotellae, fusobacteria.

PMID- 16905809
TI  - [Correlation of bleached teeth's tissue micro-durability and time of placing the
      dental filling].
AB  - Bleaching of discolored teeth has become one of the pressing issues of modern
      aesthetic dentistry in Georgia. Correct selection of endo-bleaching substances is
      crucial in resolving this issue, as it is well known that endo-bleaching agents
      penetrate into the dental tissues, causing "microcracks". Aim of our study became
      selection of right materials for dental bleaching, as well as finding additional
      methods of prevention these materials from penetrating into the dental tissue.
      Serving this aim, we have studied several types of endo-bleaching substances, as
      well as micro-durability of dental tissue, based on the numerous methods of its
      determination. Subsequently we observed the effect of endo-bleaching materials
      "endoopalescence" and "endoperox" on dental tissue. Data analysis has shown that
      there were significantly less "microcracks" found after use of "endoopalescence",
      than "endoperox". The most beneficial results were obtained during concomitant
      use of endo-bleaching material "endoopalescence" and antioxidant, since the
      latter improves micro-durability of dental tissue. Based on all of the above we
      recommend use of "endoopalescence" as an endo-bleaching substance, in complex
      with antioxidants.

PMID- 16905808
TI  - [Role of various etiologic factors in the development of burning mouth syndrome].
AB  - Burning mouth syndrome (BMS) has been comparatively recently isolated as the
      separate nosologic diagnosis. This disease is characterized by the feeling of
      burning, dryness, numbness, pricking and seldom by pain in the tongue or mouth
      cavity area (palate, lips, alveoli) without any changes in mucous membrane.
      Absence of visible causes of the disease complicates its treatment and makes the
      patients to address the physicians of various profiles, often without any result.
      All the above stated made the authors to define the etiologic factors of various
      clinical versions of BMS and to carry out their differential diagnostics along
      with the development of pathogenetic therapy of BMS. 30 women of 40 to 70 year of
      age were examined. According to the anamnesis, BMS was developing gradually and
      in most cases it was associated with the aggravation of the existing disease
      (hypertension, diabetes mellitus, aggravation of climacteric state) or with
      deterioration of psycho-emotional sphere due to conflicting situation. The
      carried out studies enabled the authors to select and divide patients with BMS
      into groups according to clinical values and the etiologic factors. In most cases
      diverse clinical versions of the burning mouth syndrome are cause-and-effect
      expressions of various somatic diseases, the timely determination and adequate
      therapy of which give the best results in the struggle against BMS.

PMID- 16905810
TI  - [Cytological issues of Curiosin's influence on the inflammatory processes in
      parodontal tissues].
AB  - A new medicine--Curiosin--was applied for treatment of inflammatory processes in
      parodontal tissues. Curiosin has no analogies by the composition and effects. It
      is the organotrophic medication, which includes Zinc and Hyaluronic acid. It is
      the glue-like, limpid solution, its pH=5-6. The Hyaluronic acid of Curiosin gets
      into contact with the fibrinous net and makes transitional matrix. It stipulates
      activity and migration of granulocytes, macrophages and fibroblasts, also - the
      proliferation of epithelial cells. The effectiveness and success of complex
      treatment was shown in 130 persons. The patients were divided into two groups:
      control group, n=59 persons and the study group, n=71 patients. The traditional
      treatment course was applied in patients of the control group. This course
      includes removing of gingival plaque, curette of periodontal recesses, medication
      of periodontal tissues with antiseptic solutions. After these preparations,
      periodontal tissues treated by heparin ointment and trichopol, also by
      periodontal bounds. In this case antibiotic-therapy was introduced. In the
      patients from the second-group Curiosin and plasma-therapy was applied. Before
      and after treatment the cytological examination was carried out in patients of
      both groups. For examination we got contents of periodontal recesses. Before the
      treatment the inflammatory processes in parodontal tissues was shown. In presence
      of ulcero-necrotic gingivitis, on 18-month post-operative cytogramms we saw the
      following results: after the treatment there was no any more processes of
      inflammatory-destructive character; the number of leucocytes and lymphocytes
      sharply decreased, while the number of undamaged cells increased. This fact can
      prove discontinuance of inflammation and induction of regenerative processes in
      periodontal tissues. We have seen the same results in groups of patients with
      periodontitis. Beside, there were the large number of undamaged epitheliocytes
      and increased number of plasmocytes.

PMID- 16905811
TI  - Comprehensive treatment of generalized parodontitis.
AB  - The complexity of pathogenesis of periodontitis makes the use of comprehensive
      treatment necessary. We observed 60 patients, 20 women and 40 men among them aged
      from 20 to 50. In the course of parodontitis, we determined the intensity of
      inflammatory-destructive changes (Pi) in the course of periodontitis, the degree
      of fang denudation, the depth of gum and parodontal recesses, degree of the teeth
      becoming loose; we conducted the microbiological study of the oral cavity
      microflora and drew up an antibiotic graph. We included laser therapy in the
      comprehensive treatment course of generalized parodontitis. We divided the
      patients into two groups. The patients of the first group were treated in two
      stages. We used peridex, composed of chlorhexidine for antiseptic treatment of
      oral cavity. We used a combined solution of sage, eucalyptus, camomile and
      calendula to irrigate the oral cavity. At the second stage we used ointment
      applications with the composition of 3% indometacin, heparin, vitamins, sea
      buckthorn oil and antibiotics. In the course of comprehensive treatment of the
      patients of the II group we included laser therapy. Our interest in the laser
      beam, as in the means of parodontitis treatment was stimulated by a number of
      properties of the laser beam and namely, its anti-inflammatory, desensitizing and
      antibacterial action promotes intensifying the reparation processes and does not
      entail any complications. The mentioned method has produced the best therapeutic
      results and has resulted in the reduced treatment period.

PMID- 16905812
TI  - [Recovery after low-flow anesthesia in elderly patients].
AB  - The study was carried out in 76 patients aged 65-84 years with the physical
      status ASA II-III, who underwent different surgical operations on abdomen under
      high and low-flow anesthesia. Awakening after anesthesia was evaluated by the
      following parameters: time between the end of intervention and extubation of the
      trachea, opening the eyes when asked, transportation from the operation room into
      the ward, and first dialogue with the doctor. A system of evaluating the level of
      recovery of respiration, motor activity, and consciousness by Aldret and
      Kroulik's score was used for objective assessment of the data. The findings show,
      that in contrast to the high-flow anesthesia, which results in a late awakening ,
      the use of low-flow technique of anesthesia allows to create good condition for
      an early activation after abdominal surgery and for reduction of postoperative
      complication in elderly and senile patients with severe comorbidity.

PMID- 16905813
TI  - [Fever of Unknown Origin in children and adolescents in Georgia: a review of 52
      patients].
AB  - The distribution of the disorders causing Fever of Unknown Origin (FUO) may
      differ according to the geographic area and the socioeconomic status of the
      country. FUO has not been appropriately investigated in children and adolescents
      in Georgia and therefore a study was undertaken to determine its causes and
      clinical characteristics. A total of 52 children fitting the classical FUO
      criteria seen in our clinic between 2003 and 2005 were investigated
      retrospectively. 27 (51,9 %) were boys and 25 (48,0%) were girls. 3 children (5,7
      %) were less than 3 years old, 4 (7,6%) were 3-9 years old, 14 (26,9 %) were 10
      14 years old and 32 (61,5%) were 15-18 years old. The mean age was 15,9 +/-4,8
      years (range 1 year-18 years). 25 children (48,0 %) had a prolonged fever that
      had lasted for 15-30 days, 15 (28.8 %) for 31-60 days, and 12 (23.0 %) had fever
      lasting for more than 60 days. The most common causes of FUO were sepsis (10/52),
      tuberculosis (9/52), pneumonia (8/52), pyelonephritis (5/52), collagen tissue
      disorder (2/52), neoplasm (2/52), and miscellaneous (9/52). In 7 (13,4 %) of the
      cases the etiology could not be found. Some derivative hematological parameters-
      leukocytic index of intoxication, organism's allergisation index, ratios
      lymphocytes/neutrophils and eosinophils/lymphocytes and adaptation reactions can
      be helpful to distinguish severe infections. Precise evaluation of hematological
      changes can be useful for differential diagnosis of FUO. The most common cause of
      FUO in children and adolescents in Georgia remains infection.

PMID- 16905814
TI  - [Indexes of a functional condition of a liver with hemolytic disease of the
      newborn stipulated incompatibility between the mother and fetus].
AB  - The hemolytic disease of the newborn, originating as a result of sensitization of
      the mother to the Rh-antigen of erythrocytes of the fetus (Rh-HDN) is one of the
      most important causes of the loss of a fetus and newborn. One of the pathogenetic
      mechanisms of Rh-HDN is the hyperbilirubinemia at the expense of the toxiferous
      fraction of a bilirubin negatively influencing many organs of the child,
      including the liver. The purpose of the work was the complex study of indexes of
      a functional condition of a liver newborn with a various degree of gravity Rh-HDN
      and definition of effectiveness of the conducted therapy. The direct association
      between severity of illness and indexes of pigmental, excretion and detoxication
      of the function of the liver in newborns with Rh-HDN has been found. There were
      found significant relations of ALT/AP, AST/AP, GT/AP, albumin and globulin
      factors with the degree of cholestasis and toxic damage of the liver. The lack of
      normalization of indexes of the peptide uptake and the excretion function of the
      liver on the background of treatment indicate to the necessity of further
      monitoring of functional condition of the liver and realization of the correction
      of therapy after discharge of children from the hospital, especially with the
      serious form of Rh- HDN.

PMID- 16905815
TI  - [Clinical value of changes in red blood cell ultrastructure and energy metabolism
      in children with cystic fibrosis of the pancreas].
AB  - In 42 patients of various age (from 1 month to 14 years) with cystic fibrosis
      were analyzed ultra structure, level of adenylnukleotides and activity of ATP-ase
      of erythrocytes, in order to characterize their membrane and energy metabolism .
      Our recent studies revealed increase of ATP-ase and decrease of ATP of
      erythrocytes, in children both with bronchopulmonary and mixed form of cystic
      fibrosis. In patients with lethal outcome were detected more significant decrease
      of the ATP combined with increase of ATP-ase in erythrocytes then in other cases,
      which is resulted not only by suppressed glycolic processes but also by exhausted
      compensative-adaptive abilities of the human organism in whole. In patients with
      cystic fibrosis were detected changes both in quantity and quality of
      erythrocytes' stereoultrastructure: the level of the discocytes was significantly
      decreased, while the level of all other 12 types of erythrocytes were increased,
      also there were detected appearance of erythrocytes with pathogenic forms. The
      changes mentioned above were more apparent in patients with mixed form of cystic
      fibrosis and lethal outcome. The results of our study have a great value for
      medical practice providing more precise diagnosis, in time correction of
      disorders and a comprehensive assessment of multiple-modality treatment of cystic
      fibrosis.

PMID- 16905817
TI  - [Estimation of effectiveness of the prevention of sudden cardiac death in
      patients with myocardial infarction].
AB  - On the basis of open, randomized, inspected trial during 1 year period, the
      effectiveness of inclusion in the standard treatment of beta blockers, metoprolol
      and Carvedilol for prophylaxis of sudden cardiac death has been investigated. 112
      patients with a myocardial infarction in the age of from 45 till 70 years from
      the contingent of the IV hospital of Tbilisi were included in the trial. Absolute
      and relative risk reductions were defined. Statistical analysis was performed by
      chi2 (Pearson) criterion using SPSS 11.5. The relative risk of SCM in the group
      of patients who got the treatment by Carvedilol was 0,28 (95% CI: 0,12-0,62),
      relative risk reduction of SCM was 0,97 (95%CI: 0,59-0,99), absolute risk
      reduction - 0,30 (95%CI: 0,15-0,45).

PMID- 16905816
TI  - Assessment of early age healthy Georgian children's physical, motor and
      psychosocial development by BINS (Bayley Infant Neurodevelopmental Screener).
AB  - Physical, motor and psychosocial development has been studied in healthy Georgian
      infants and early age children who were born without biological risks.
      Neurological, receptive, expressive and cognitive functions were assessed by BINS
      (Bayley's Infant's Neurodevelopmental screener). Comparing to the norm given by
      BINS, analyses of variances shows a significant difference of median sum
      indicators in all age groups. Depression of expressive and cognitive functions
      are mainly the reason of this difference, which can be defined by the incorrect
      management of social adaptive steps. The process of management is incorrect
      because of the deficiency of mother, as a standard person's role in the issues of
      children growth and development. The analyses of our material showed, that BINS
      is one of those remedies which timely and exactly identifies child's psychosocial
      development. On the other hand, child's incomplete socialization makes issue of
      parents' educational system to become more perfect. Study results shows that
      above mentioned problem are caused by incorrect management of social adaptive
      steps, which is based on the deficiency of mother as a standard person in the
      process of child's growth and development.

PMID- 16905818
TI  - [Epidemiological study of coronary heart disease, cerebrovascular diseases and
      their risk-factors].
AB  - To study the incidence of coronary heart disease (CHD), cerebrovascular diseases
      (CVD), combined pathology (CHD and CVD) and their risk factors such as arterial
      hypertension (AH), overweight (OW), hypercholesterolemia (HC) and tobacco smoking
      in the same population, a random representative sample of male and female
      populations were examined in Vake districts of Tbilisi. AH and tobacco smoking
      were found predominant among men, whereas OW and HC among women. It turned out
      that almost every fourth person out of the men and almost every second women
      suffered from cardiovascular diseases. In men, the CHD?CVD ratio was 1:1, that in
      the women, was 1:7. In the men and women, suffering from combined pathology, AH
      occurred more frequently as compared to those with CHD or CVD alone. OW promoted
      the development of CVD and combined pathology in women to a greater degree,
      whereas HC favoured the development of CHD and CV D in men.

PMID- 16905819
TI  - [Peculiarities of bone metabolism in healthy men of Georgian nationality].
AB  - The purpose of the present research was studying parameters of the bone
      metabolism and bone mineral density in the context of the risk - factor of
      osteoporosis among young healthy men. 56 practically healthy men in the age of 22
      37 years were investigated. With the help of ultrasonic densitometry cases of
      osteopenia and osteoporosis were revealed. The received data confirm opinion
      about non-uniform bone mineral density among men of young age. This indicate to
      the importance of early detection of cases of osteoporosis among the healthy
      population with the purpose of conducting timely preventive measures.

PMID- 16905820
TI  - Attentional disorder in vascular dementia.
AB  - Clinical trials in vascular cognitive impairment are in their infancy. The
      current narrow definitions of vascular dementia (VaD) should be broadened. VaD is
      characterised by a specific cognitive profile involving preserved memory with
      impairments in attentional and executive functioning. The present study aimed at
      a) Investigating whether VaD/pts showed the marked decrease in selective
      attentional functioning different from the healthy ageing population; b)
      Determining norms for the Digit Symbol Coding (DSC) task performance for the
      Georgian elderly population. Case-control study of selective attentional
      performance was conducted by forming groups of 15 VaD/pts (mean age M=65,6;
      SD=8,64), 64 young (aged 17-25 years with M=20,69; SD=2.97) and 64 healthy old
      subjects (aged 50-75 years with M=59,77; SD=7,13). Severity levels of dementia
      determined by MMSE. VaD/pts were administered the qualitative assessment
      procedure of aphasia for excluding the cases with aphasia. The selective
      attentional functioning was studies by the DSC task. A statistically significant
      difference was detected on the DSC task for the three study groups
      F(2,62)=87,030, p<.0001 using one-way ANOVA. Norms for the selective attention
      functioning were prepared for the Georgian elderly population. The study results
      showed that attentional disorder is a prominent characteristic of VaD. The DSC
      task reveals ageing effect and differentiates performance of VaD/pts from the
      performance of normal elderly participants.

PMID- 16905821
TI  - [Efficacy of chophytol in complex treatment of patients with the chronic forms of
      hepatitis and cirrhosis of viral etiology].
AB  - The preparation chophitol in complex treatment significantly improves the life
      quality of patients with chronic hepatitis and liver cirrhosis of viral etiology.
      It normalizes the index of cytolysis (ALT, AST) in patients with chronic
      hepatitis of viral etiology with moderate activity, and also the level of
      bilirubin in significantly short periods of time. In patients with liver
      cirrhosis of viral etiology classified as Child-Pugh A and B after the treatment
      with chophitol has been normalized index of overall protein and albumin, and in
      patients with liver cirrhosis classified as Child-Pugh class C appeared a
      tendency to the normalization of overall protein and albumin and prothrombin
      index, also creatinine in blood, which was accompanied with increased diuresis.
      The preparation is not expensive, is well tolerated. There has been observed no
      side effects on the treatment.

PMID- 16905822
TI  - [Intensity of metabolic syndrome in patients with different degrees of obesity].
AB  - Metabolic syndrome is a complex disorder and an emerging clinical challenge. It
      is considered a "multiplex" cardiovascular risk factor, in that each component of
      the cluster of abnormalities is a risk factor in its own right. Introduced as
      Syndrome X by Reaven in 1988 and also termed insulin resistance syndrome,
      metabolic syndrome is recognized clinically by the findings of abdominal obesity,
      elevated triglycerides, atherogenic dyslipidemia - i.e. low levels of high
      density lipoprotein cholesterol (HDL-C), elevated blood pressure, high blood
      glucose and/or insulin resistance. The goal of our research was to investigate
      intensity of "complete metabolic syndrome"- (abdominal obesity, dyslipidemia,
      elevated blood pressure, high blood glucose and/or insulin resistance) in
      patients with different degrees of obesity. In our study 570 patients have been
      involved. The patients were divided into 3 groups: I group--123 patients with
      first degree of obesity (body mass index - BMI - 30-34,9 kg/m2), II group--189
      patients with II degree of obesity (BMI - 35-39,9 kg/m2), III group--258 patients
      with III degree of obesity (BMI >40 kg/m2). Results of carried out investigations
      have shown that the complete picture of metabolic syndrome was present in 132
      (23,16%) patients and should note, that according to the increasing of obesity
      degrees also increases the intensity of metabolic syndrome.

PMID- 16905823
TI  - [The effectivenes of traction influence in a complex treatment of the spine's
      thoracocervical osteochondrosis].
AB  - The efficacy of implementation of isolated autogravitational extension as well as
      in complex with rehabilitation-recovery measures on neurological manifestations
      thoracocervical osteochondrosis of spine were investigated in this work.
      Investigation of traction influence conducted on the 57 patients with
      thoracocervical osteochondrosis of spine in the acute stage has shown distinct
      therapeutic effectiveness of autogravitational extension in the presence of
      reflex manifestations of thoracocervical osteochondrosis, it's normalizing effect
      on the muscular-tonic changes, vertebral disorders including pain syndrome.
      Efficacy is achieved by applying autogravitational extension with gymnastic
      exercises and massage. Therapeutic effect when lying on the traction couch
      achieved due to equal traction effort in all section of spine. At the compression
      manifestations of thoracocervical osteochondrosis in the acute stage with pain
      syndrome efficacy of autogravitational extension is lower then at the reflex that
      basically is connected with impossibility of initial full relax.

PMID- 16905824
TI  - Higher and lower extremity vein color duplex sonography in highly qualified
      football players and wrestlers.
AB  - It is recognized that due to muscle exercises cardio-vascular system undergoes
      various morphologic and functional changes among highly qualified sportsmen.
      Healthy vascular system is needed to meet successfully great physical load. Aim
      of the search was to study higher and lower extremity venous system functional
      condition during physical exercise and rest among highly qualified football
      players and wrestlers. Highly qualified 30 wrestlers and 25 football players of
      age 18-25 years were studied. Olympic, World and Europe champions were included
      among wrestlers. Apparatus Acuson 128 X P/10 performed color duplex sonography
      examinations, transducers 7.5 MHz lineal. Higher and lower extremity venous
      screening in B regime was simultaneously performed by blood stream color
      cartogram and blood stream spectral analysis. Study revealed no pathology and
      documented about even rates among football players and wrestlers for higher and
      lower extremities by color duplex sonography. B-regime revealed same
      echonegativity of lower extremity veins among wrestlers and football players.
      Target veins were distinguished by echopositive vessel wall lineal structure. In
      color duplex regime venous lumen were evenly filled with color. Sportsmen post-
      physical exercise color duplex sonography examination revealed higher extremity
      venous lumen diameter and blood stream parameters twice exceeded among wrestlers
      than football players. However, time needed for the venous lumen diameter and
      blood stream changes was equal for both groups of sportsmen. The study revealed
      that football player lower extremity medial and wide calibre venous diameter 2.5
      3 fold increased during post-exercise examination; lower extremity venous
      diameter and blood stream restores to primary parameters 30 min earlier in soccer
      players than in wrestlers. Thus, higher and lower extremity veins react in
      different ways among sportsmen of different kinds. For example lower extremity
      vein diameter and blood stream increases in football players more than in
      wrestlers, while, higher extremity veins reach higher rates in wrestlers to
      compare to soccer players. These evidences conclude different adaptation
      resources among sportsmen of different physical trainings. That is why during
      physical load blood circulation in down to up direction is facilitated because of
      lower extremity muscle contraction support in football players.

PMID- 16905825
TI  - [Influence of treatment with variable magnetic field of low frequency in low
      mountain environment on cardiohemodynamic index of patients with arterial
      hypertension].
AB  - Pathological changes in function and action of cardiovascular system is the
      significant link in formation and progression of arterial hypertension. 68
      patients were investigated. From these patients in 32 first stage of mentioned
      pathology, while in 36 - the II degree was found. It is established that
      treatment of arterial hypertension by variable magnetic field of low frequency in
      low mountain environment causes decrease of systolic, diastolic and heart dynamic
      blood pressure, normalizes heart index and pulse rate; decreases peripheral
      vascular specific resistance, increases amount of upset index accelerated of
      blood flow on the region "lung-ear", improves electrocardiological data.
      Mentioned pathological displacements were more expressed at the first stage of
      arterial hypertension.

PMID- 16905826
TI  - [Study of epidemiological situation of HIV associated TB in Georgia].
AB  - The goal of the work is to study epidemiological situation of TB/HIV coinfection
      in Georgia. The research was based on the study of TB prevalence among 766
      HIV/AIDS patients registered at the National Centre of Infections Diseases, AIDS
      and Clinical Immunology in 1989-2004; determining of HIV status among 3084
      patients with active TB, treated in the hospital of the National Centre of TB and
      Lung Diseases, Abastumani TB-hospital and Ksani prison Analysis of the obtained
      data showed that dynamic of TB/HIV coinfection in the period of 2000-2004 varied
      from 2,1% to 3,8%. Results show low indicators of HIV associated TB prevalence in
      Georgia. Taking into account slow but stable increase of HIV/AIDS new cases and
      complicated, but manageable epidemiological situation in regard to TB, increasing
      of the cases of HIV associated TB can be expected.

PMID- 16905827
TI  - [Evaluation of the preserved skin graft viability by O2 consumption test].
AB  - This study provides a description of the functional changes occurring in rat skin
      grafts preserved at 4 C in natural honey during 3, 7, 14, 30 days. To determine
      of the preserved skin viability we used the physiological test by measurement of
      O2 consumption rate in the culture media. O2 consumption measurement provided by
      Zieger MA, et al. For control was used normal and dead skin samples. Normal skin
      O2 consumption rate was considered as 100% viability, and dead skin - 0%.
      Preserved skin O2 consumption rate per 3, 7, 14, 30 days was - 72%, 38%, 15%, 8%
      respectively. Natural honey is antiseptic and cryoprotective material. Based on
      our investigation we can conclude that preservation method--meliteration is
      effective storage procedure for transplantation means (satisfactory viability
      preserved about 2-3 weeks). At the same time O2 consumption test gives us
      objective information about tissue viability potential. This method is very
      simple and useful for scientific investigation and practical medicine.

PMID- 16905828
TI  - [Influences of some homeopathic preparations on ionic homeostasis at different
      dilutions].
AB  - Considerable number of the investigations are dedicated to the study of the
      influences of the various agents on ionic homeostasis of the cell. However, there
      are actually no works related to the impact on these indices of homeopathic
      preparations (HP). In the present work influence of HP - stimulated phosphoric
      acid (PA), at low dilutions (10(-14) and 10(-42)) and non-stimulated PA, at high
      dilutions (10(-200) and 10(-400)), on transmembrane transport of Na+, K+, Ca2+,
      and enzymes - Na,K-ATPase and Ca-ATPase - was investigated. Experiments were
      carried out by means of ion-selective electrodes, in order to measure
      concentration of ions in the Ringer solution. Results have shown that HP at low
      dilution always stimulated observed indices, while HP at high dilution -
      suppressed these indices. Therefore, driving force of HP increases with dilution,
      because number of hydrate complexes increases and so does velocity of information
      transmission, which is responsible for different effects.

PMID- 16905829
TI  - [The role of oxidative stress in pathogenesis of obesity].
AB  - Recent findings on fat metabolism open new prospective for developing effective
      drugs that would focus on white adipose tissue as therapeutic target. The aim of
      our study was establishment of features of oxidative metabolism in adipose tissue
      in diet-inducible obesity (DIO) model in rats and under influence of citrus. By
      the result of our investigations it may be concluded, that adipose tissue plays
      important role in development of oxidative stress during obesity. In DIO model in
      adipose tissue it was revealed disorders of mitochondria electron transport
      chain, excess generation of reactive oxygen species and lipoperoxides,
      inactivation of superoqsiddismutasa, intensification of lipid peroxidation and
      development of oxidative stress. Citruses by the normalization of body lipid
      metabolism promotes normalization of mitochondrial electron transport, decrease
      of oxidative stress, restoration of adipocytes' metabolism.

PMID- 16905830
TI  - Pyramidal cell loss in hippocampus of young rats exposed to toluene.
AB  - In the present study the influences of toluene intoxication on quantity of the
      pyramidal and granular cells in hippocampus was analysed in young and adult rats.
      An inhalation route of intoxication was used in our experiments - animal inhaled
      toluene until attaining a sidewise laying position. This procedure was performed
      in the closed glass container, in which air was beforehand saturated with the
      toluene vapors. Experiments was carried out on two age groups (n=20): one and two
      months age rats. Inhalation period was 40 days, Each age group consisted of ten
      animals and was divided into the two subgroups: I - control animals (n=5), II -
      experimental animals (n=5). Assessment of the neurons' quantity in different
      structures was made according to the fractional approach method proposed by M.
      West. The results obtained showed that number of the pyramidal neurons decreases
      by 26% (I - 1067+/-83,8; II - 786+/-7; p<0,05) against the control in CA-3 field
      of the Subgroup II of the younger animals only. In the dentate fascia number of
      the granular cells does not change in either age group. Loss of pyramidal cells
      in the CA-3 field will induce deterioration of the hippocampal neural circuits
      and destroy of memory and learning processes in the rats.

PMID- 16905831
TI  - [Investigation of physical activity among adults].
AB  - Lack of physical activity as well as smoking, overweight, high blood cholesterol
      level and hypertension are independent risk factors for development of various
      chronic diseases. Lack of physical activity is a main cause of non-communicable
      diseases morbidity and mortality in about 23% of cases (WHO, 2002). Goal of the
      survey was the identification and characteristics of physical activity among
      adults. We conducted epidemiologic survey among the school-children and students
      in Tbilisi. Survey was carried out in 40 schools from all regions of Tbilisi and
      9 state and private institutes. Schools were selected by randomized trail in each
      region of Tbilisi and in each school were questioned all teen-agers from 14-17
      year old. For selecting group of survey was used method of "proportional
      probability of value". There were questioned 2 500 school children and 1000
      students, 38% boys and 62% girls. The results of survey ascertained that 23,5%
      39,5% of respondents are training or engaged in sport everyday, or several times
      per week; 17,2% - once in a month; 9,3% once in a year; or 10,5% - never. Adults
      are less informed about useful effect of physical activity. Respondents had
      different point of on the role of physical activity: some of them thought it
      controls weight; others - prevents development of different diseases; the rest
      thinks that it copes with psycho-emotional stress, and none of them precise about
      effectiveness of physical activity in all cases mentioned above. Propaganda of
      healthy life stile must be associated with the effectiveness of physical activity
      on health.

PMID- 16905832
TI  - [Change of concentration endothelin-1 in rats on a background of alcohol and /or
      mildronate treatment].
AB  - Alcoholic cardiomyopathy is specific cardial pathology characteristic for chronic
      consumption of alcohol. Endothelin-1 is an endothelium-derived potent
      vasoconstrictor peptide, which level directly influence the severity of this
      condition. Mildronate is an antiischemic drug. It inhibits carnitine biosynthesis
      (suppress beta-oxidation of the fatty acids) and increases the production of
      nitric oxide in the vascular endothelium. The aim of the study was to establish
      how Mildronate influences concentration of ET-1 in blood of rats on a background
      of chronic consumption of alcohol and at abstinence. White rats (n=28) instead of
      drinking water were taking 15% ethanol with the following regimens: A) three-week
      alcohol consumption, B) after 3 weeks of alcohol consumption on a background of
      alcohol they took mildronate, C) four-week alcohol consumption; D) after 4 weeks
      alcohol consumption they took only mildronate. Concentration of ET-1 in the group
      A was 6,00 +/- 0,35 fmol/ml, in the group B - 4,82 +/- 0,31 fmol/ml, in the group
      C - 13,25 +/- 0,49 fmol/ml and in the group D - 9,17 +/- 0,17 fmol/ml.
      Consumption of alcohol concentration ET-1 in blood high, for this purpose it is
      enough also 3-week alcohol consumption; the concentration of ET-1 progressively
      elevates with increase of duration of alcohol consumption; mildronate lowers
      concentration of ET-1 both on the background of alcohol consumption and on the
      background of acceptance of alcohol; under influence of mildronate the condition
      is improved in parallel the with complete alcohol consumption and acceptance of
      alcohol.

PMID- 16905833
TI  - [Changes in emotional state and learning process disorders in rats with
      experimental hepatic encephalopathy].
AB  - Animal models of liver failure are widely used for research of morphological and
      functional changes and pathogenetic mechanisms of hepatic encephalopathy. Changes
      in learning process and emotional state of rats, which were administered
      intraperitoneally (Phenobarbiton 40 mg/kg/day) for five days and then
      subcutaneously (Acetaminophen 1000 mg/kg) are described. Behaviour of rats was
      studied in the "open field". Experimental animals in comparison with the control
      group had decreased position-finding-exploring activity although the motor
      activity and the fear feeling level weren't changed. The testing in the multi
      branch maze showed that the experimental animal's learning ability was greatly
      decreased--from the start platform of the maze to the nest they made more
      mistakes and spent more time than the control group animals, and even at the end
      of the maze session successful completion of task (to reach the nest) wasn't
      exceeding 60%.

PMID- 16905834
TI  - [HLA antigens and the process of operative wound healing].
AB  - Association of HLA antigens with wound healing process was investigated in
      Georgian patients. Based on the peculiarities of the wound healing process
      dynamics, two groups of patients have been distinguished. The first group
      included 22 patients with primary intention of the operative wounds, while the
      second group included 30 patients with complicated course of the wound healing
      process. Control group was comprised by 492 healthy persons. Our study showed
      that the distribution of HLA antigens is different in these groups. The
      genetically determined risk of development of wound complications was
      significantly higher in individuals with HLA-DR1 having the relative risk 3,56.

PMID- 16905835
TI  - [Rare case of huge echinococcus of the liver].
AB  - A huge echinococcus, 26-16 cm in size, of the right lobe of the liver was
      diagnosed by means of echoscopy and radiology in the man 53 years of age. During
      operation 3000 ml of transparent liquid with daughter bubbles were taken out from
      the echinococcus cavity. Partial resection of the right lobe of the liver and
      drainage of the echinococcus cavity were made transhepatically with two
      drainages. During the postoperative period everyday sanitation of the cavity with
      antiseptic solutions was done. Periodically echoscopic monitoring of the
      echinococcus cavity was also done. The cavity gradually decreased in volume and
      after three months it was closed.

PMID- 16905836
TI  - [Surgical treatment of lung echinococcosis form the view of close and later
      results].
AB  - Close and later results in 67 patients after echinococcectomy have been studied.
      45 of these patients had the organ saving resection and 22 had different kinds of
      resection of lung (lobectomy, segmentectomy, atipical resection). Among organ
      saving operations 21 patients were treated with video-assisted thoracoscopic
      surgery (VATS). There were no cases of disease recurrence and mortality. The best
      results have been achieved after minimal invasive surgery. In all cases good
      results have been retained. There were no complications during postoperative
      period, hospital stay was 5-6 days, early rehabilitation of all patients was
      achieved. Complications were observed in 9 cases from 45 patients after
      traditional surgery. After traditional echinococcectomy cases of disability have
      not been reported. Among all patients decrease of working ability has been
      developed in 7.8% cases, which could be considered satisfactory.

PMID- 16905837
TI  - Investigation of the microflora and the principles of treatment of infected open
      tissue defects.
AB  - Treatment of chronic defects of the body remains a difficult problem. Despite the
      achievements in reconstructive surgery, the failure incidence is high. Infection
      in the chronic defect region plays the leading role in the pathogenesis.
      Therefore the outcome of the disease highly depends on the study of the
      microflora of chronic defects and the choice of optimal methods of infection
      control. There are data testifying to the fact that the schemes of empirical
      antibiotherapy which have proved their effectiveness in one country, may turn out
      to be ineffective in another country. 176 cases of chronic tissue defects of
      various duration (up to 4 and more years) were analyzed. Changes of the
      microflora and microbe resistance were traced. High incidence of strains
      resistant to most antibiotics is observed in chronic defects. The microflora
      formation is in many respects associated with an inadequate administration of
      antibiotics. On the basis of the obtained results, practical recommendations are
      given on the use of antibacterial preparations. One-stage operations and the
      transplantation of well-vascularized tissues are the principal methods of
      treatment against the infection in a tissue defect, which are no less important
      than the methods of choice in treating large infected chronic defects of the
      body.

PMID- 16905838
TI  - Surgical management of renal cell carcinoma invading the inferior vena cava.
AB  - The aim of the study was the evaluation of long-term outcome and prognosis of the
      patients with renal cell carcinoma (RCC) extending into the inferior vena cava
      (IVC). Influence of the patient, tumor characteristics and therapeutic
      interventions on the disease prognosis was also assessed. 24 patients (19 male
      and 5 female) with RCC extending into the IVC underwent surgical treatment at our
      institution between 1990 and 2002. The mean patient age was 58.2 years (range: 38
      78 years). The level of tumor extension was infrahepatic (level I) in 16 (67%),
      intrahepatic (level II) in 6 (25%) and suprahepatic without atrial invasion
      (level III) in 2 (8%) patients. All the tumors were resected via inferior vena
      cava; median sternotomy with a control of supradiaphragmatic IVC without
      cardiopulmonary bypass and hypothermia was performed in two cases. Mortality rate
      was 7.5 %. Complications occurred in 6 patients (25 %). The 5-year Kaplan-Meier
      survival estimate was 65%, with a mean follow-up of 49.6 months (range: 10-152
      months). The tumor grade, radicality of tumor excision and symptoms at the
      disease presentation (systemic vs. local) were the factors associated with the
      disease-free survival (p=0.02, 0.002 and 0.03, respectively). There was no
      significant difference in survival with regard to the level of thrombus extension
      into the vena cava (p=0.3) Surgical treatment is preferred option in the patients
      with RCC and IVC tumor thrombus as it provides markedly better results as
      compared with other therapeutic modalities. The complete surgical excision of the
      primary RCC and the tumor thrombus with appropriate preoperative staging and
      surgical technique provides an acceptable long-term patient survival with a good
      quality of life.

PMID- 16905839
TI  - [Effect of patients' preoperative condition on the outcome of the surgical repair
      of the infrarenal abdominal aortic aneurism].
AB  - During the past decades there is an evidence of the increase in the number of
      patients with the aneurism of the infrarenal abdominal aorta (IRAAA). As a rule,
      there is an increased operative risk among these patients due to presence of
      concomitant diseases. The aim of this study was to investigate effect of
      patients' preoperative condition on the outcome after the surgical repair of the
      IRAAA. We studied 78 patients with IRAAA, who underwent elective surgery during
      1982-2006. Age ranged from 30 to 84 with the main age of 64. Concomitant diseases
      were detected in 99% of patients. Postoperative complications occurred in 55% and
      in 14% there was a lethal outcome. The effect of patients' preoperative condition
      on the postoperative course was investigated. The role of the thorough
      preoperational evaluation in an effort to reduce complications in the
      postoperative course was emphasized.

PMID- 16905840
TI  - [Evaluation of effectiveness of radiation therapy for regional control in
      supraglottic larynx cancer].
AB  - The supraglottic cancer is characterised by high incidence of regional metastasis
      significantly worsening the prognosis. Working out of an adequate regional
      control represents the one of the important problems. The aim of the study was
      the evaluation of pre-operative radiation therapy in 331 patients with N-negative
      supraglottic cancer. Three groups of patients were analyzed: I-radiation
      therapy/laryngectomy, II-laryngectomy/radiation therapy, III-only laryngectomy.
      It was found that the main prognostic factors of regional metastasis are:
      extension, differentiation, ulceration and growth pattern of tumor. The pre
      operative radiation therapy is reasonable for effective regional control. The
      fact that the regional recurrence is developing faster in patients not conducted
      the radiation therapy at all is also indicating on the above-mentioned. Despite
      the fact, that the regional control is improving with pre-operative radiation,
      the overall survival of supraglottic cancer could not be regarded adequate, which
      requires the further study in terms of evaluation of preventive neck dissections
      with laryngectomy is this group of patients.

PMID- 16905841
TI  - [Study of serum levels of magnesium in the patients with malignant tumors].
AB  - The main goal of the study was the evaluation of serum levels of magnesium in the
      practically healthy persons (control group), the patients with different
      malignant tumors (abdominal, pulmonary, uterus, breast, esophagus, rectum), as
      well as benign tumors of the breast/the uterus and the inflammatory pulmonary
      diseases. Content of Mg in blood serum was determined using the method of atomic
      absorption spectrophotometry. It has been found that, in comparison with norm
      (23.9 mkg/ml), there is statistically significant increase in serum mean levels
      of Mg in the patients with malignant tumors of almost all sites investigated.
      Abdominal/breast and lung malignant tumors are exclusive from this point of view:
      we have found that Mg content is near the normal mean levels in the former cases
      (24.7 mkg/ml and 25.3 mkg/ml, respectively) and below the average normal value in
      lung malignant tumors (20.5 mkg/ml). It has been ascertained that there is no
      significant difference between the serum average levels of Mg in the control
      group and in the patients with pulmonary inflammatory diseases, as well as
      between the Mg-content in practically health persons and in those with breast
      benign tumors. Thus, assessment of serum Mg levels seems to be useful in
      differential diagnosis in oncopulmonary and oncomammology clinics.

PMID- 16905842
TI  - Usage of the product of the Italian company "President" for the treatment of
      inflammatory diseases of periodontium.
AB  - Unsatisfactory hygienic condition of mouth cavity is one of the main reasons of
      periodontitis and gingivitis. The purpose of the investigation was the evaluation
      of effectiveness of the product of Italian company "President" for curing
      inflammatory diseases of the periodontal tissues. 42 patients aged from 18 to 65
      were under observation. With the general and local anti-inflammatory treatment
      they were prescribed the following tooth-pastes: President Active, President
      Exclusive, and President Sensitive; rinses: President Profi, President sensitive
      plus, gel for gums--President Sensitive Plus. We used unique toothbrushes:
      President Gold, President z3, President Silver Care. The patients of the second
      group used desired toothpastes, eliminators and toothbrushes. The patients
      studied before and after the treatment was defined by the hygienic indices: HI,
      OHI, GI, PI. Microbiological investigations have shown high sensitivity of
      "President" product to Candida type fungi. Treatment results have shown that the
      data of clinical indices in both groups came nearly up to the norm, but in the
      first group its significance turned to be lower then in the second group.
      According to the results of the investigation we can sum up that the product of
      Italian company "President" secures essential improvement of hygienic state of
      mouth cavity, has antimicrobial and anti-inflammatory effect and its using is
      effective for curing and prophylaxis of periodontal tissues inflammatory disease.

PMID- 16905843
TI  - [Effectiveness of treatment with selenium electrophoresis in patients with
      ischaemic cardiac disease with a stable stenocardia of tension].
AB  - The increasing trend to the growth of cases of ischaemic cardiac disease and,
      first of all, cases of a stable stenocardia of tension and lethal outcome make
      topical the search of new effective etiopathogenic means for prophylaxis and
      treatment of this pathology. The goal of this investigation was to study
      effectiveness of treatment with selenium electrophoresis of patients with ICD:SST
      of the I-II functional classes (FC). Total of 76 patients with ischaemic cardiac
      disease have been investigated. Among them a stable stenocardia of tension of the
      I functional class was observed in 31 patients and SST of the second II FC - in
      45 patients. It has been established that in patients with a stable stenocardia
      of tension the treatment with selenium electrophoresis evokes a slackening right
      up to absence of complaints; has a normalizing action on cardio-hemodynamics;
      improves oxygen provision of the organism increasing saturation of arterial and
      venous blood with oxygen; increases tolerance to physical loading and volume of
      fulfilled work; decreases changes in frequency of systole and arterial pressure
      under the influence of physical loading and restitution. Mentioned shifts
      decreased according to intensification of the pathology. The treatment had a
      positive action on all patients with SST of the I FC and 41 patients with a
      stable stenocardia of tension of the II FC. The treatment was inefficient in 4
      patients with SST of the II FC.

PMID- 16905844
TI  - [The influence of psychosocial factors in developments of ischemic heart disease
      and arterial hypertension in persons with genetic predisposition].
AB  - The purpose of the work was to investigate the influence of psychosocial factors
      on the development of ischemic heart disease and arterial hypertension in persons
      with genetic predisposition to cardiovascular disease. Three groups of patients
      were investigated: 72 patients with AH, 175 patients with IHD (74 with angina
      pectoris and 101 with angina pectoris and myocardial infarction) and 164 patients
      with IHD and AH. In nearest relation of 283 (69/03%) patients from 410 were found
      the presence of high arterial hypertension, myocardial infarction, diabetes and
      obesity. In this persons reliable relationship were found between psychosocial
      and genetic factors (in persons with genetic predisposition to cardiovascular
      disease were found high rate of anxiety, frequent stressful situations at work
      and in family, psychoemotional overloads). On the basis of our investigations it
      may be concluded that the genetic and psychosocial factors together play
      important role in the development of IHD and AH, that perhaps caused from
      influence of genetic factors on capable of to overcome the stress.

PMID- 16905845
TI  - [Effect of perindopril on indices of cardiac function and quality of life in
      patients with arterial hypertension in regard to age].
AB  - At present in the treatment of arterial hypertension the role of angiotensine
      converting enzyme inhibitors is significant. From this group the most special
      attention was attracted to peridopril-esbumin. High efficiency of this
      preparation has been corroborated by numerous controlled, multicentral
      investigations. Study of the effect of dosage and peculiarities of peridopril
      appears to be the most important taking into account age factor that has been
      insufficiently studied. The goal of our investigation was to study effect of 4 mg
      and 8 mg of peridopril on functional indices of the heart of patients with
      hypertonic disease and their psychoemotional sphere in the aspect of age. Total
      of 78 patients with hypertension and without clinical manifestations of cardiac
      insufficiency, diabetes mellitus and having had myocardial infarction were
      examined. According to the age patients were divided into two groups: <65 and
      >65. The investigations lasted for 12 months. Besides ECG investigations,
      patients were subjected to echoscopic and doplerographic investigations. For the
      estimation of life quality a questionnaire of evaluation of general health state
      (SF-36 Health Status Surveu) containing 11 questions was used. It was shown that
      peridopril has the different action among patients of different age groups. In
      older patients (>65 years) it increases indices of physical activity, while in
      younger patients it has a beneficial effect on the emotional parameters.

PMID- 16905846
TI  - Hemorheological, microvascular and hemodynamic disorders during coronary heart
      disease.
AB  - Significance of the hemorheological disorders in development of acute vascular
      syndromes is presently well known, but their role in pathogenesis of chronic
      coronary heart disease has not been yet sufficiently analyzed. Aim of the present
      study was the investigation of the relationship between the hemorheological,
      vascular and hemo-dynamic factors responsible for development of the coronary
      heart disease. We investigated 64 patients with coronary heart disease of the
      functional classes I-IV with and without the heart failure. For evaluation of the
      hemorheological disorders we investigated its most significant symptom, the
      erythrocyte aggregability, with the "Georgian technique" that provided us with
      direct and quantitative data. We investigated also the tone of the hand's
      resistance arteries with an original non-invasive technique based on measurement
      of the flow velocity changes in the patients and in the healthy controls radial
      arteries by using the Doppler technique during standardized postischemic
      hyperemia. Echocardiographically we studied the standard characteristics of left
      ventricular function (systolic and diastolic volume, its mass and ejection
      fraction). ECG by standard leads and the blood pressure were investigated in all
      patients. We found that the rheological disorders are manifested in the early
      stages of the disease before its functional manifestation. The most pronounced
      hemorheological disorders were in evidence in the patients with unstable angina
      and heart failure. As to the arteriolar resistance index, it was increased only
      in 45 per cent of all the investigated patients and no significant difference
      between the patients with the heart failure and without it was found. There was a
      negative relationship between erythrocyte aggregability and the ejection fraction
      of the left ventricle and the positive correlation between erythrocyte
      aggregability and left ventricle hypertrophy (p<0.01). We concluded that the
      blood rheological disorders represent themselves a factor that plays a
      significant role in pathogenesis of the coronary heart disease. They are
      predictors of the disease and not only risk factors as it is generally believed.
      Measurement and correction of these disturbances in its early stages have a high
      clinical significance.

PMID- 16905847
TI  - [Peculiarities of metabolic characteristics in females of reproductive age with
      hyperplastic processes of cervix and mammary glands].
AB  - The aim of our investigation was the evaluation of character of metabolic
      disorders in patients with hyperplastic processes of uterine corpus, cervix and
      mammary glands. 88 patients of reproductive age with several gynaecological
      complaints have been investigated. 72 patients with hyperplastic processes of
      endometrium and endocervix (hyperplasia, polyposis), myoma of uterus,
      fibroadenoms and adenomatosis of mammary glands were selected in main group.
      Control group consisted of 16 patients without any hyperplastic processes of
      genital organs. Metabolic syndrome in main group was revealed in 28% of cases, in
      control--18.8% (chi(2)=3.95, p=0.047); insulin resistance--30.5% and 18.7%
      (chi(2)=4.01, p=0.046), respectively. In main group in comparison with control
      group took place the tendency of the increase triglyceride plasma level and the
      decrease of levels of HDL-cholesterol. b-cell function was significantly
      increased in patients with hyperplastic processes of uterine corpus and cervix,
      in subgroup of uterine myoma revealed the tendency. Insulin resistance revealed
      in patients with hyperplasia of endocervix and pathologies of mammary glands. Our
      results suggest that metabolic syndrome and its components significantly
      influences on the formation of hyperplastic processes of uterine corpus, cervix
      and mammary glands.

PMID- 16905848
TI  - Efforts of identifying the place of tb infection and bcg vaccination in the
      hygiene hypothesis of allergy.
AB  - Hygiene hypothesis of allergy proposed by D. Strachan in the 1980s is still
      urgent. The goal of the study was the identification of association between BCG
      vaccinations and TB infection and bronchial asthma and other allergic
      manifestations and defining the nature of such association. The study engaged
      students of the Tbilisi secondary school #4, born in 1990-1998. The study was
      carried out using International Study of Asthma and Allergies in Childhood
      questionnaire and tuberculin test. The obtained data was statistically processed
      using computer software Epi-info (Version 3.3.2. Atlanta, USA). The conclusions
      of the study are as it follows: 1. There is no statistically reliable association
      between BCG vaccination and prevalence of Bronchial asthma, as well as other
      allergic manifestations. This makes doubtfull involvement of anti-TB immunization
      in hygiene hypothesis. 2. Incidence of bronchial asthma and other allergic
      manifestations among TB infected individuals is twice lower in comparison with
      non-infected persons. Despite this fact due to non-representativity of the
      material such inverse association is not statistically reliable.

PMID- 16905849
TI  - [The age dynamics of the factors of the CRS functioning training of teenagers'
      organisms under identical physical load].
AB  - The age dynamics of the factors of the Cardio-Respiratory System (CRS)
      functioning training and its influence on the identical direction as well was
      carried out on 33 sportsmen of different specializations. The testing sportsmen
      were divided into two groups: Group I--conditionally--stayers with higher indices
      of the maximum oxygen consumption (VO(2max)) from the beginning; Group II-
      conditionally--sprinters with relatively low initial indices of VO(2max). It is
      concluded that the development of the factors of the CRS functioning training has
      a heterochronic character. The factor increase of the aerobic power, economicity
      and stability is mostly revealed in teen-agers, with higher primary values of
      VO(2max). before the training beginning. The negative correlation in dynamics of
      aerobic and anaerobic productivity power has not been revealed. It is shown, that
      the aerobic power of CRS reaches the limits of the reaction norm on the early
      stages of the age development as compared to the anaerobic power.

PMID- 16905850
TI  - [Damage of iron metabolism and oxidoreduction process in children with beta
      thalassemia].
AB  - beta-thalassemia is the most common monogenic hereditary blood disease in
      children. It is also considered to be the regional pathology for Georgia. The
      influence of iron metabolism disorder on metabolic processes taking place in
      erythrocyte membrane and their role in pathogenesis of beta-thalassemia, is very
      important until now. The aim of our research was to study the condition of
      oxidoreduction processes in RBC membranes on the background of iron metabolism
      disorder in children with beta-thalassemia. We observed 44 patients with beta
      thalassemia aged 0.4-14 years. Iron, ferritin, malon-dialdehyde and catalase were
      evaluated. The carried out investigation revealed, that oxidoreduction processes
      in patients with beta-thalassemia, together with iron overload, is one of the
      factors in promoting further disorder of proliferation and differentiation
      processes in erythrone system and also in formation of ineffective
      erythropoiesis. The revealed changes in data of iron metabolism. malon-dialdehyde
      and catalase showed us the need for correction of this disorder. Pathogenetically
      there are good reasons to include in the combined treatment beta-thalassemia the
      membrano-protective preparations (vitamin E, acetylcysteine) together with the
      hemotransfusion and chelator therapy.

PMID- 16905851
TI  - [Monitoring of neopterin and INF-gamma in children with recurrent respiratory
      tract infection].
AB  - The upper and lover respiratory tract infections are usually mild and self
      limited. Owing to their frequency recurrent upper and lower respiratory tract
      infection in children and adults constitute a major global health problem. The
      goal of our study was to observe 30 children with recurrent respiratory tract
      infection, 17 boy and 13 girl, they were treated with Ribomunyl. The control
      group consisted of 15 children who received only basic therapy (10 boys and 5
      girls). The age of the children ranged between 8 months and 6 years. The study
      was conducted by the simply randomization method. Clinical and laboratory
      examinations were evaluated before and after treatment. The concentration of INF
      gamma was rather low in study group in comparison with control group before the
      beginning of the treatment, that indicates insufficient stimulation of T
      lymphocytes in children with recurrent infection. INF-gamma lever significantly
      increased after treatment (Statistically significantly P<0.05) in study group in
      comparison with control group. Neopterin level unlike INF-gamma in study group
      was higher than in the control group, before and after treatment. This fact can
      be explained that neopterin as a slowly acting biologically active substance
      remains high during the presence of recurrent infections. Ribomunyl treatment
      significantly increased the level of neopterin. The efficacy of the product is
      primarily confirmed by significant reductions in the number of recurrent
      infections episodes and the use of antibacterials. Combined immunostimulating
      effect of Ribomunyl makes it possible to use Ribomunyl to create a longterm
      postvaccinal protection of the child.

PMID- 16905852
TI  - [Interferon system in children with cystic fibrosis].
AB  - Parameters of interferon-producing leukocyte function were studied in vitro, in
      32 patients of different age (from 1 month to 14 years) with cystic fibrosis and
      30 normal children. Mixed form of cystic fibrosis were detected in 20 patients,
      while bronchopulmonary form were found in 12 patients. According to Shvaxman
      scale 16 patients had 40 point (severe), 13 patient had 41-45 point (moderate)
      and 3 patient had 56-70 point (mild). The interferon was studied using the
      Soloviov-Bektemirov technique in the A. Natishvili Institute of Experimental
      Morphology of Georgian Academy of Sciences. Interferon level varied between 0 and
      2 U/ml both during the acute phase and remission, while the normal level would be
      at 4-24 U/ml. Therefore, interferon therapy can be recommended as part of
      combined treatment, particularly at an early stage of acute respiratory viral
      infection, during epidemic outbreaks and in hospital where patient should only be
      admitted (and kept in individual cubicles) after outpatient treatment for
      aggravations of the disease proved ineffective.

PMID- 16905853
TI  - [The role of oxidative metabolism in pathogenesis of hyperbilirubinemia in
      infants].
AB  - The aim of the study was the investigation of free radical oxidation intensity in
      blood of newborn infants with hyperbilirubinemia. In infants blood the bilirubin,
      free nitric oxide, lipoperoxide radicals Fe(2+)-ions, methemoglobin, oxy- and
      desoxy hemoglobin content, erythrocytes deformability and resistance were
      studied. Results of the study testify the intensive generation of free nitric
      oxide, release of ferritin-free ferrous (Fe(2+)), intensification of
      lipoperoxidation, decrease of red blood cells resistance, and accumulation of
      methemoglobin in blood of newborn infants with hyperbilirubinemia. The low
      content of nitric oxide in blood is due to its oxidative transformation to
      peroxynitrite. NOO(-)-inducible hemolysis of erythrocytes is one of promoters of
      hyperbilirubinemia in infants. It was concluded, that the reason of infants
      hyperbilirubinemia is intensification of oxidative stress, formation of excessive
      nitric oxide, enhancing of red blood cells haemolysis and it promotes disturbance
      of erythrocytes membrane, decrease of their resistance and deformability,
      intensification of haemolysis and extrication of redox-active iron.

PMID- 16905854
TI  - [Neuroendocrine, neorophysiological and neuropsychological changes in children
      form the iodine deficient population with endemic goiter].
AB  - The study was performed in Chokhatauri region, on students of age 13-14 in
      village Meria in 36 schools. There is discovered mild iodine deficiency with
      median variation from 78 to 96 %. After clinical and ultrasound studies, it was
      identified endemic goiter (83.33%). There was performed multi-profile clinical
      studies on young people by neurologists, neurophysicians, endocrinologists,
      pediatricians. Electroencephalographic study was performed by digital equipment
      by visual and computer analysis of the results. There were identified brain
      functional changes of diffuse character in EG writings. It was identified
      multineurological complains, especially in children with endemic goiter. With
      neurophysiologist's tests was estimated neurocognistic functional studies, as in
      people with endemic goiter also with healthy ones. According to test scores, was
      estimated perception of visual-space construction, speed of intellectual task
      performing, quality of functional recognition. According to the results, was
      estimated visual space memory. The scores in children with endemic goiter was
      lower then in healthy children. The results are giving possibility to estimate in
      children with endemic goiter mild neuro-endocrinology, neuro-physiology and neuro
      physiology changes coursed by iodine deficiency, before infringement in their
      clinical appearance. In time prevention of this infringement will give us
      possibility to avoid future pretended infringement in intellect development.

PMID- 16905855
TI  - [Treatment of obstruction of extrahepatic biliary pathways by antireflux, bilio
      cholecystic (cystico) enteroanastomosis methods].
AB  - The main target of our investigations was the development of antireflux, bilio
      cholecysto (cystico) enteral anastomosis method for the surgical treatment of
      extrahepatic biliary duct obstruction. We were using the cholecystic duct spiral
      valve (Lutkens valve, Haister valve) as the antireflux structure. In this case
      the bile drains into the biliary cyst not through the cholecystic duct but
      through the extrahepatic biliary duct - the bilio-cholecystic anastomosis. Such
      an interposition of cholecystic and spiral valves promotes inhibition of chemical
      reflux between extrahepatic ducts and gastrointestinal tract, from digestive
      tract into the cholecystic and intrahepatic biliary tracts. Method developed and
      tested by us involves creation of blio-cholecystic (cystico) entero anastomosis,
      namely creation of biliary duct-cholecystic (cystico)-duodenoanastomosis. 3
      successful experimental operations have been performed using the above presented
      approach. Sutures were taken of on the seventh day, animals were housed under
      investigations for 10-14 days, faecal masses had normal appearance.

PMID- 16905856
TI  - [Effect of hypoxic-ischemic preconditioning of neonatal rats--morphometric
      evaluation of cerebral hemispheres].
AB  - Though the mechanisms of hypoxic-ischemic preconditioning are under
      investigation, it is considered that nitric oxide can play a critical role in the
      formation of this phenomenon. Experiments on white rats for study of cerebral
      hemisphere masses were carried out on 22-nd day after 3-hours hypoxic-ischemic
      exposure: (a) on 7-day-old rats, (b) on 7-day-old rats but 30 minutes before this
      exposure animals 3-times underwent short lasting (5 minutes) hypoxic-ischemic
      impacts (preconditioning), (c) same as previous experimental condition, but 15
      minutes before beginning of preconditioning, animals were intraperitoneally
      injected either by non selective nitric oxide synthase (NOS) inhibitor (L-NAME)
      or (d) inducible NO synthase (iNOS) selective inhibitor--aminoguanidine. Received
      results showed that 3-times preconditioning efficiently protect brain from three
      hours hypoxic-ischemic exposure. It is evident that nitric oxide play a critical
      role in this protection--it completely eliminated morphological manifestation of
      hypoxic-ischemic preconditioning while aminoguanidine--just partially decreased
      the volume of brain hypoxic-ischemic ischemic damage.

PMID- 16905857
TI  - [Treatment of thrombophlebitis by the method of the transplantation of the
      endothelial cells].
AB  - The end XX of century was marked by introduction into the clinical practice of
      the methods of cellular therapy. Intensive studies on its application for
      treating the whole series of diseases are conducted. Thrombophlebitis is not an
      exception in spite of the already existing effective surgical and conservative
      methods of its treatment. On the rabbits we produced experiments on the treatment
      of thrombophlebitis of "aseptic" and infectious etiology. The results of complex
      treatment with the use of autologous vascular endothelial cells were studied. The
      damaged wall of vein under the conditions of the "aseptic" model of
      thrombophlebitis, with conducting active complex therapy with the start of
      antibiotics and trombolitic means is completely covered with endothelium, and
      only to the place where the dust devils were attached to the walls of vein,
      defects remain. In these places the wall of vein gradually is extended and
      undergoes scarring, and the intact sections of vein around the defect are
      hypertrophied and then they undergo dilatation, being adapted thus to the new
      conditions of functioning. The transplanted endothelial vascular cells not only
      modify the process of remodulation of the damaged vein and thus they contribute
      to averting the dilation of its wall and expansion of scar, but also contribute
      to the retention of the thickness of the wall of vein. Calculations showed that
      in the case of "aseptic" etiology the processes of thrombogenesis and treating
      thrombophlebitis continue more rapidly than in the case of the infectious
      etiology. The comparison of traditional method of the treatment of
      thrombophlebitis with the complex (with the application of auto of endothelial
      cells) showed that the latter is more effective.

PMID- 16905858
TI  - [Optimisation of the conditions of particle sizing of gentamicin sulfate].
AB  - One of the problems for the development of dry powder inhalation preparations is
      evaluation of particle size distribution of obtained micronized powders for the
      determination of theoretical aerodynamic diameter of the particles. The final aim
      of our study is the development of inhalation dry powder formulation of
      gentamicin sulfate, therefore it is necessary to determine theoretical
      aerodynamic diameter of micronized gentamicin sulfate particles. Micronized
      gentamicin sulfate powders are very cohesive and do not have satisfactory flow
      properties, the shape of the particles is close to spherical. The most suitable
      technique for this kind of powders is laser diffraction. On the basis of realized
      experiments the optimal conditions for the determination of particle size
      distribution of gentamicin powders were found. Results are in accordance with the
      data obtained by method-reference (Electron Microscopy).

PMID- 16905859
TI  - [Influence of some homeopathic preparations on tumor cells].
AB  - The goal of the study was the assessment of action of homeopathic preparations on
      ionic homeostasis in the cells of Ehrlich carcinoma (CEC). Continuous recording
      of Na(+), K(+), and Ca(2+) with selective electrodes in the Ringer solution was
      used as a main method. Activity of the enzymes controlling transmembrane
      transport of ions was monitored as well. It was shown that homeopathic
      preparation - stimulated phosphoric acid (PA), at low dilutions (10(-14) and 10(
      42)), stimulates ionic transport and Na,K-ATPase in CEC. Non-stimulated PA, at
      dilutions of 10(-200) and 10(-400), contrariwise, hampers these indices. It is
      concluded that structuring of preparation increases with increased number of
      dilutions and, respectively "concentration of information field" increases as
      well. Transfer of information from initial substance occurs probably in a course
      of dilution. Such is the concept of some of the homeopathics.

PMID- 16905860
TI  - Isolated hepatocytes stimulation activity on toxic liver failure in experimental
      study.
AB  - Finding of affective treatment methods of acute liver failure (alf), consists one
      of difficult solving problem in modern hepatology. To day improving liver
      transplantation methods for the stimulation of regeneration process.
      Transplantation of liver allogenic isolated hepatocytes in A.L.F.treatment,
      promotes regeneration morphological capabilities of toxically damaged liver. We
      used combined enzymatic-mechanical method modified by Korukhov (1983), which let
      to take up 50-60% of cells from liver mass, 80% from them maintained their
      morphological structure and functional activity. Experiments were performed on 45
      white laboratory rats. Animals were divided into 3 groups. I group of animals
      (n=20) was the control group, with acute liver failure without treatment, in this
      group, lethal outcome was 100% in the I group, after CCL4 administration on 5 and
      7 days. II group (n=20) included animals who had ALF model and which provides
      treatment with isolated hepatocytes transplantation. III group of animals were
      served as donors for isolated hepatocytes uptake. 90% of animals from II group
      were alive after treatment during 20 days and then their condition was
      satisfactory. Biochemical and morphological investigation proved that our
      treatment method induces toxically damaged liver function restoration.

PMID- 16905861
TI  - [Morphological peculiarities of consolidation of experimental mandible fractures
      by osteosynthesis using Kollapan and retabolil].
AB  - The Purpose of the research was to study in the experiment morphological
      particularities of mandible fracture consolidation by osteosynthesis using
      Kollapan and Retabolil. The experiments were carried out on sexually matured
      rabbits. In the first series of the experiments (the control group), mandibula
      bones fracture was prototyped lower, whereas bone fragments were fixed by
      miniplate. In the second series of the experiments (the study group) bone
      fragments were bolted by the above mentioned way but diastase between bone
      fragments was filled by Kollapan granules, containing klaforan, and animals were
      intramuscularly anabolic material (the retabolil 0.4 mg/kg). On the 3-d and 15-th
      days, as well as, after 1 and 2 months after operation observing all
      corresponding rules, animals were killed and patologico-anatomic study of jaw
      bone was carried out. The analysis of the results showed that in experimental
      animals both in the control and the study groups reparative regeneration of bone
      tissues runs with the formation of periosteum and intermedium regenerator, at the
      same time consolidation of the bone defect in the main group occurs earlier than
      in the control group. The Results of the studies point out that Retabolil under
      osteosynthesis is an osteoinductive material and Kollapan, having osteoinductive,
      osteoconductive, and osteoprotective characteristics, promotes speeding of the
      process of jaw bones fracture consolidation.

PMID- 16905862
TI  - The characteristics of human papillomavirus expression and cell proliferation in
      actinic keratosis and Bowen's disease of the skin.
AB  - The aim of our study was to elucidate the characteristics of HPV expression and
      cell proliferation in actinic keratosis and Bowen's disease of the skin. We
      examined immunocompetent patients with premalignant lesions of the skin such as
      actinic keratosis and Bowen's disease. 10 patients were involved in each group.
      Clinical study included gross features of lesion, growth rate, colour, size.
      Paraffin sections from biopsy specimens were were stained by hematoxylin-eosin
      and von Gieson. Immunohistochemistry was performed using monoclonal antibodies
      against HPV, oncoprotein p53, anti-apoptotic protein Bcl-2, proliferation marker
      PCNA. Strongly, moderately and weakly positive cells were counted. Actinic
      keratosis and Bowen's disease failed to show the specific clinical features,
      therefore, they can not be diagnosed based on clinical signs only and
      morphological examination seems to be mandatory. The immunohistochemical study
      has showed that in both actinic keratosis and Bowen's disease HPV was positive in
      60%, and 40% were HPV-negative suggesting the similar incidence of HPV infection
      in these premalignant lesions. Our results suggest that HPV(+)/p53(+) types of
      actinic keratosis and Bowen's disease are characterized by higher proliferation
      activity in comparison to HPV(-)/p53(+) types, and expression of Bcl-2 is
      associated with HPV-negativity, therefore, these premalignant lesions of the skin
      require immunohistochemical examination with evaluation of expressions of human
      papillomavirus, proliferation marker PCNA and anti-apoptotic protein Bcl-2. The
      differential diagnosis of actinic keratosis and Bowen's disease should be based
      on the following immunohistochemical criteria: incidences of positivity for p53,
      Bcl-2 and PCNA are similar, but expression intensity and anatomical localization
      are different: their expressions are higher in Bowen's disease, positive cells
      are found primarily in upper epidermis in actinic keratosis, while whole
      epithelium is involved in Bowen's disease.

PMID- 16905863
TI  - [Extra-islet cells of pancreas during the diabetes of alloxan and after the
      action of plaferon].
AB  - Using the methods of light and electron microscopy, pancreas was studied in the
      experimental model of alloxan diabetes (AD) at various times of the experiment (1
      and 6 month) at different degrees of AD and after the action of plaferon. The
      special emphasis was made on display of compensatory changes that is opportunity
      of occurrence in extra-islet cells special granules, characteristic for insulin
      producing B-cells. During the development of pathological processes, there were
      detected intermediate cells including exocrine and endocrine granules. Some of
      these cells were located near the acini and some of them were in close contact
      with duct cells. It is suggested that these intermediate extra-islet cells are
      especial cells with high functional activity, they are transitional form during
      the processes of transformation into endocrine ones, possibly these cells are
      precursors of islet cells. It is possible, that plaferon acts on processes of
      transformation and differentiation of extra-islet cells and takes part in
      neogenesis of B-cells.

PMID- 16905864
TI  - [For periodization of history of fight against TB in Georgia].
AB  - Evolution of TB programs indicates the importance of analysis of existing
      experience and reasons of failure in planning of TB strategy for future. In spite
      of existing scientific researches in the field of history of fight against TB in
      Georgia, it turned out that the question is not mastered perfectly, various
      periods are not sorted out and the comparative analysis is not made. On account
      of this, a request was raised to elaborate a new periodization. The aim of our
      research is to work out a new variant of periodization of history of fight
      against TB in Georgia. Epidemic, literary and the official statistical data were
      worked out by the methods of historical analysis and standardization. According
      to the research, it turned out that the correlation exists between social 
      political state and the spreading of TB, which was reflected in our "step"
      pattern. It means to serve as criteria of spreading of tuberculosis and TB
      strategy. Concerning these criteria a new variant of periodization was elaborated
      and the separate stages were compared. It gives us opportunity to determine
      effective methods and measures and they should be envisaged in the condition of
      realisation DOTS strategy in Georgia.

PMID- 16905865
TI  - [Health peculiarities among georgian national ballet dancers].
AB  - Dancers performing classical, characteristic and national dances represent one of
      those activities that cause stress of nervous-muscular and psycho-emotional
      systems, locomotion apparatus induced by physical efforts. Intensive physical and
      psycho - emotional stress during the dancing process causes misbalance between
      physiological possibilities of the body and its capability of prompt adaptation,
      thus creating conditions for developing pathologies. Among male dancers of
      Georgian national ballet most frequently occur professional diseases such as:
      arthrosis and traumatic meniscites of knee joints, arthrosis of talocrural joint,
      epicondylitis of shoulder bone, chronic lumboiliac sacriplex radiculitis, and
      osteochondrosis of cervical part of the spine; among female dancers
      osteochodrosis of neck and chronic lumboiliac radiculitis were mainly observed.
      Increased level of neurasthenic syndrome among dancers of Georgian national
      ballet occurred in the form of hypertonic type vegetative-vascular dystonia. That
      stemmed from peculiarities of dancers work and permits to ascribe this pathology
      to the group of work-related diseases. To this group should be ascribed as well
      podagra arthritis of a foot stemmed from: a) systematic micro-traumas resulting
      in dystrophic changes and b) special regimen of nutrition.

PMID- 16905866
TI  - [Peculiarities of cell wall ultrastructure of Nocardia dassonvilei].
AB  - Peculiarities of cell wall building and chemical content of Nocardia dassonvilei
      have been studied in conditions of culture growth and development. It has been
      established that according to the phases of actinomyces a mass of cell wall
      changes. In particular, it is maximal in logarithmic phase and minimal - in
      stationary phase. In the phase of dying an insignificant increase of cell wall is
      noted. It appears to be a result of the increase of amino acid content in peptic
      fraction of peptide-glycane in this phase. At the same time it has been
      established that according to the growth phases, in cell wall of the studied
      actynomyces the amount of teihoic acid appears to be a changeable value. In
      particular, it decreases from logarithmic to the phase of dying. The content of
      cell wall free polysaccharides also changes; their synthesis begins in
      logarithmic phase, reaches to maximum in stationary phase and is minimal in the
      phase of dying. According to the results of our investigations it has been
      established that chemical content of Nocardia dassonvilei cell wall is
      qualitatively stable in the dynamics of culture growth.

PMID- 16905867
TI  - [Peculiarities of development of rat's audiogenic convulsive responses in the
      period of gestation].
AB  - In rats, with genetically determined audiogenic epileptic seizure some
      peculiarities of convulsive responses before and during gestation as well as
      after the delivery were studied. Depending on responses to audio stimuli the rats
      of Krushinsky-Molodkina line might be divided on two groups. The responses of
      first group are: fear and facial muscles clonus; the responses of other group-
      fear, wild running and then development of clonic and tonic seizures. The rats of
      this (second) group were used in our experiments. In the period of gestation: (a)
      extended latency of development of convulsive activity; (b) significant
      prolongation of the intervals between wild running and (c) marked reduction of
      behavioral manifestation of clonic and tonic seizures have been observed. These
      indicate the strengthening of inhibitory processes in the brain. It is supposed
      that in the period of gestation in rats with genetically determined to
      development of audiogenic seizures excess of sexual hormones causes the gaining
      of anticonvulsive processes in the brain. Evidently, this should be connected
      with GABA-ergic inhibitory mechanisms of the brain.

PMID- 16905868
TI  - [Social-psychological factors of fertility].
AB  - Study of social-psychological factors of fertility and the reasons of its
      reduction in the regions of Georgia from the standpoint of reproduction behavior
      is the subject of our research. The sociologic inquiry carried out among women of
      fertile age dwelling in the Imereti Region gave us the corresponding information
      for analysis. Altogether 1462 forms were analyzed. Research revealed that the
      result of reproduction behavior is directly affected not only by the rate of
      evidence of separate multiplier of reproduction purpose, but by its integrity as
      well. Social-psychological factors influence the birth rate through the mediation
      of values, motives, purposes. Comparison of the groups of women by their
      orientation towards different values showed that the respondents with high
      reproduction purpose have all the values concerned with family getting higher,
      though the orientation towards material well-being remains rather high. The
      results of the research revealed (during elaboration of measures of demographic
      policy) the necessity of consideration of distinguishing features of the region.

PMID- 16905869
TI  - Strategies to maintain the stability of the ribosomal RNA gene repeats-
      collaboration of recombination, cohesion, and condensation.
AB  - Ribosomal RNA gene repeats (rDNA) are one of the most characteristic regions in
      eukaryotic chromosomes. The repeats consist of more than 100 tandem units
      occupying large part of the chromosome in most of organisms. Cells are known to
      deal with this "unusual domain" in a unique manner. In this review, I will
      summarize work on rDNA repeat maintenance, focusing mainly on work done by our
      group, and show that the maintenance mechanism operates by a collaboration of
      recombination, sister-chromatid cohesion, and chromatin condensation.

PMID- 16905870
TI  - Subcellular localization of a germiantion-specific cortex-lytic enzyme, SleB, of
      Bacilli during sporulation.
AB  - The subcellular localization of a germination-specific cortex-lytic enzyme, SleB,
      of Bacillus subtilis during sporulation was observed by using fusions of N
      terminal region of SleB to the green fluorescent protein (GFP). A fusion with a
      putative peptidoglycan-binding motif (SleB1-108-GFP) formed a fluorescent ring
      around the forespore of the wild type strain, as expected from the known location
      of the intact SleB in the dormant spore. SleB1-108-GFP formed a similar
      fluorescent ring around the forespore of the gerE mutant which has a severe
      defect in the coat structure, and of the cwlD mutant which lacks a muramic delta
      lactam unique to the spore peptidoglycan (cortex), whereas the fusion could not
      attach to the spore of the cwlDgerE mutant. By contrast, a fusion without the
      motif (SleB1-45-GFP) could not be recruited around the forespore of the gerE
      mutant though it appeared to be accumulated on the outside of the spore of the
      wild type strain. Since SleB was shown to degrade only the cortex with muramic
      delta-lactam, these results suggested that a proper localization of SleB requires
      a strict interaction between the motif of the enzyme and the delta-lactam
      structure of the cortex, not the formation of normal coat layer.

PMID- 16905871
TI  - Two OsGASR genes, rice GAST homologue genes that are abundant in proliferating
      tissues, show different expression patterns in developing panicles.
AB  - Two different types of genes for rice GA-stimulated transcript (GAST) homologue
      genes, Oryza sativa GA-stimulated transcript-related gene 1 (OsGASR1) and gene 2
      (OsGASR2), were found. Both OsGASR proteins contain a cysteine-rich domain highly
      conserved among GAST family proteins in their C-terminal regions. Gibberellin A3
      (GA3) stimulated expression of both OsGASRs in the wild-type Nipponbare and GA3
      synthesis-deficient mutant. Expression of both OsGASRs apparently increased when
      cell proliferation entered the logarithmic phase, and rapidly reduced when cell
      proliferation was temporarily halted. RT-PCR analysis indicated different
      expression patterns of these genes in developing panicles. OsGASR1 was limitedly
      but strongly expressed in florets while OsGASR2 was expressed in both florets and
      branches. In situ hybridization showed that they were strongly expressed in the
      root apical meristem (RAM) and shoot apical meristem (SAM), but little signals
      were detected in mature leaves. Transient expression of OsGASR-GFP fusion
      proteins in onion epidermal cells revealed that both OsGASR proteins localized to
      the apoplasm or cell wall. These results suggest that OsGASR1 and OsGASR2 were
      involved in cell division and might play diverse roles in differentation of
      panicles.

PMID- 16905873
TI  - Genetic interactions underlying hybrid male sterility in the Drosophila
      bipectinata species complex.
AB  - Understanding genetic mechanisms underlying hybrid male sterility is one of the
      most challenging problems in evolutionary biology especially speciation. By using
      the interspecific hybridization method roles of Y chromosome, Major Hybrid
      Sterility (MHS) genes and cytoplasm in sterility of hybrid males have been
      investigated in a promising group, the Drosophila bipectinata species complex
      that consists of four closely related species: D. pseudoananassae, D.
      bipectinata, D. parabipectinata and D. malerkotliana. The interspecific
      introgression analyses show that neither cytoplasm nor MHS genes are involved but
      X-Y interactions may be playing major role in hybrid male sterility between D.
      pseudoananassae and the other three species. The results of interspecific
      introgression analyses also show considerable decrease in the number of males in
      the backcross offspring and all males have atrophied testes. There is a
      significant positive correlation between sex - ratio distortion and severity of
      sterility in backcross males. These findings provide evidence that D.
      pseudoananassae is remotely related with other three species of the D.
      bipectinata species complex.

PMID- 16905872
TI  - Phylogenetic analysis of diprotodontian marsupials based on complete
      mitochondrial genomes.
AB  - Australidelphia is the cohort, originally named by Szalay, of all Australian
      marsupials and the South American Dromiciops. A lot of mitochondria and nuclear
      genome studies support the hypothesis of a monophyly of Australidelphia, but some
      familial relationships in Australidelphia are still unclear. In particular, the
      familial relationships among the order Diprotodontia (koala, wombat, kangaroos
      and possums) are ambiguous. These Diprotodontian families are largely grouped
      into two suborders, Vombatiformes, which contains Phascolarctidae (koala) and
      Vombatidae (wombat), and Phalangerida, which contains Macropodidae, Potoroidae,
      Phalangeridae, Petauridae, Pseudocheiridae, Acrobatidae, Tarsipedidae and
      Burramyidae. Morphological evidence and some molecular analyses strongly support
      monophyly of the two families in Vombatiformes. The monophyly of Phalangerida as
      well as the phylogenetic relationships of families in Phalangerida remains
      uncertain, however, despite searches for morphological synapomorphy and
      mitochondrial DNA sequence analyses. Moreover, phylogenetic relationships among
      possum families (Phalangeridae, Petauridae, Pseudocheiridae, Acrobatidae,
      Tarsipedidae and Burramyidae) as well as a sister group of Macropodoidea
      (Macropodidae and Potoroidae) remain unclear. To evaluate familial relationships
      among Dromiciops and Australian marsupials as well as the familial relationships
      in Diprotodontia, we determined the complete mitochondrial sequence of six
      Diprotodontian species. We used Maximum Likelihood analyses with concatenated
      amino acid and codon sequences of 12 mitochondrial protein genomes. Our analysis
      of mitochondria amino acid sequence supports monophyly of Australian
      marsupials+Dromiciops and monophyly of Phalangerida. The close relatedness
      between Macropodidae and Phalangeridae is also weakly supported by our analysis.

PMID- 16905874
TI  - Further evidence for recombination between mouse hemoglobin beta b1 and b2 genes
      based on the nucleotide sequences of intron, UTR, and intergenic spacer regions.
AB  - Nucleotide sequences of the intron regions and UTRs (Untranslated regions) of the
      hemoglobin beta adult genes, b1 and b2, and of the intergenic spacer region were
      determined for mouse strains representing the d, p, and w1 hemoglobin haplotypes
      defined by protein electrophoretic analyses. The hypothesis of recombination of
      the b1 and b2 genes between the d and w1 haplotypes previously reported in the
      cDNA nucleotide sequences was confirmed by neighbor-joining analyses of the
      intron regions and UTRs within the b1 and b2 genes, suggesting that all of the
      structures of hemoglobin beta adult genes support the hypothesis that the p
      haplotype was established by hybridization between d and w1 haplotype mice. The
      resultant recombinant of the p haplotype was found to have a d-like b1 gene and a
      w1-like b2 gene. In addition to the possible recombination, a break point was
      suggested around 2-3 kb downstream of the b1 gene within the intergenic spacer
      region, despite the absence of clear properties that could stimulate the
      recombination machinery. Some large insertions or deletions (indels) specific to
      the p or d haplotypes were located within the intergenic spacer region, in which
      the 1010-bp indel specific to the p haplotype was shared by all examined strains
      representing the p haplotype.

PMID- 16905875
TI  - Mitochondrial microsatellite variability in common wheat and its ancestral
      species.
AB  - On the basis of the entire mitochondrial DNA sequence of common wheat, Triticum
      aestivum, 21 mitochondrial microsatellite loci having more than ten
      mononucleotide repeats were identified. The mitochondrial microsatellite
      variability at all loci was examined with 43 accessions from 11 Triticum and
      Aegilops species involved in wheat polyploidy evolution. Polymorphic banding
      patterns were obtained at 15 out of 21 mitochondrial microsatellite loci. The
      number of alleles per polymorphic microsatellite ranged from 2 to 5 with an
      average of 3.07, and the diversity values (H) ranged from 0.09 to 0.50 with an
      average of 0.29. These values are almost two third of wheat chloroplast
      microsatellite values, indicating that variability of mitochondrial
      microsatellite is much less than that of chloroplast microsatellite. Based on the
      allele variation at all loci, a total of seven mitochondrial haplotypes were
      identified among common wheat and its ancestral species. Three diploid species
      showed their own specific haplotypes and timopheevi group (11 accessions) had
      three types, whereas 29 accessions of emmer and common wheat groups shared the
      same haplotype. These results indicate that a single mitochondrial haplotype
      determined by microsatellite analysis has conservatively been maintained in the
      evolutionary lineage from wild tetraploid to cultivated hexaploid species.

PMID- 16905876
TI  - Different amounts of DNA in each mitochondrion in rice root.
AB  - The DNA content of individual mitochondria in rice root cells was analyzed by
      fluorescence microscopy. Differences in DNA content were detected between
      individual mitochondria. Some mitochondria contained no detectable nucleoid (DNA
      protein complexes). The percent of mitochondria with DAPI(4',6-Diamidino-2
      phenylindole) -stained nucleoids varied over the length of the root (root base,
      33%; middle portion of root, 41%; root tip, 91%). The mean amounts of DNA per
      mitochondrial nucleoid were equivalent to 46.4 kbp in the root base, 52.0 kbp in
      the middle portion of root and 124.2 kbp in the root tip. The amount of DNA in
      individual mitochondria and the ratio of mitochondria with visible nucleoids were
      higher in the root tip than in other parts of the root. The estimated amount of
      DNA in almost all of the observed mitochondria was smaller than the amount of DNA
      equivalent to the rice mitochondrial genome size (490 kbp), even in root tip.

PMID- 16905877
TI  - Effects of bovine serum albumin and trehalose in semen diluents for improvement
      of frozen-thawed ram spermatozoa.
AB  - In this study, two following experiments were performed to improve post-thaw
      motility and viability of frozen-thawed ram spermatozoa. We examined i) the
      effects of different concentrations of bovine serum albumin (0, 0.3, 1, 5, 10 and
      15% BSA) in semen diluents lacking egg yolk and ii) the effects of four semen
      diluents, fructose (F: control) and trehalose (T) in semen diluents containing
      egg yolk, 15% BSA in semen diluents without egg yolk (BSA), and modified
      phosphate buffered saline (m-PBS). Frozen-thawed spermatozoa were examined for
      progressive sperm motility, viability, morphological abnormality, sperm tail
      swelling test, and sperm acrosome integrity. In Experiment 1, the rates of sperm
      motility immediately after thawing (0 h) were significantly (P<0.05) higher in
      the 10 and 15% BSA groups (55.0 +/- 2.9 and 58.3 +/- 6.7%, respectively) than in
      the positive control (F) group (41.7 +/- 4.4%). The rate of sperm viability in
      the negative control (0% BSA) group (80.2 +/- 3.3%) was significantly (P<0.05)
      lower than in the positive control (F) group (89.8 +/- 1.5%), but when compared
      with the F group, no significant differences were found among the 0.3, 1, 5, 10
      and 15% BSA groups at 0 h. The rates of sperm morphological abnormality of the 10
      and 15% BSA groups (6.5 +/- 1.3 and 6.3 +/- 1.1%, respectively) were
      significantly (P<0.05) lower at 0 h than that in the 1% BSA group (16.3 +/-
      5.2%). In Experiment 2, T addition improved (P<0.05) the post-thaw motility
      compared with the F and BSA groups. Furthermore, at 3 and 6 h, the post-thaw
      motility of the T group (36.3 +/- 2.4 and 25.0 +/- 2.0%, respectively) was
      significantly (P<0.05) higher than in the BSA (26.3 +/- 2.4 and 18.8 +/- 1.3%,
      respectively) and F (28.8 +/- 3.8 and 18.8 +/- 2.4%, respectively) groups. The
      post-thaw sperm motility and viability in the m-PBS group were significantly
      (P<0.05) lower than those of the control (F), T, and BSA groups throughout all
      observation points. These results indicate that 10 and 15% BSA can be substituted
      for egg-yolk for ram semen diluent and that the addition of trehalose enhances
      motility and viability of ram spermatozoa after freezing and thawing.

PMID- 16905878
TI  - In vitro culture conditions using chemically defined media for in vitro matured
      and intracytoplasmically inseminated porcine oocytes.
AB  - The present study investigated in vitro culture methods [droplet and Well of the
      Well (WOW)] using semi-defined and defined media [modified porcine zygote medium
      (mPZM)] and the additional effects of insulin on in vitro matured and
      intracytoplasmically inseminated porcine oocytes. In Experiment 1, in vitro
      matured and intracytoplasmically inseminated porcine oocytes were cultured for 6
      days in the following four groups: 1) mPZM-3 (containing bovine serum albumin) +
      droplet (30 mul), 2) mPZM-3 + WOW, 3) mPZM-4 (containing polyvinyl alcohol) +
      droplet, and 4) mPZM-4+ WOW. The culture media (mPZM-3 and mPZM-4) and methods
      (droplet and WOW) did not significantly affect the cleavage rate, but the
      blastocyst rate of the oocytes cultured in mPZM-3 was significantly (P<0.01)
      higher than that of mPZM-4 (20.1 and 9.4%, respectively). The blastocyst rates as
      percentages of the cleaved oocytes (51.8 and 16.9%) and the hatched blastocyst
      rate as percentages of the number of blastocysts (12.3 and 2.2%) were also
      significantly (P<0.01) higher in mPZM-3 compared with those in mPZM-4. There was
      significant interaction (P<0.05) between the two main factors; the effects of the
      culture media and methods on the rate of hatched blasyocysts as percentages of
      the blastocysts produced and, the hatched blastocyst rate (20.3%) as percentages
      of the number of blastocysts produced in mPZM-3 were significantly (P<0.05)
      higher than in the other groups. In Experiment 2, the additional effects of
      insulin (100 ng/ml) in mPZM-3 and mPZM-4 media was investigated in the WOW
      culture system. Insulin addition did not improve cleavage, blastocyst formation,
      or the number of cells in blastocysts. However, as in Experiment 1, mPZM-3
      resulted in a significantly higher blastocyst rate as percentages of the cleaved
      oocytes than mPZM-4 (33.9 and 18.4%). These results indicate that a chemically
      defined medium (mPZM-4) needs to be improved to provide more suitable culture
      conditions for in vitro development of in vitro matured and intracytoplasmically
      inseminated porcine oocytes. However, the WOW system may be a useful IVC method
      for blastocyst development of in vitro matured porcine oocytes following ICSI
      when a semi-defined medium (mPZM-3) is used.

PMID- 16905879
TI  - From selective thalamotomy with microrecording to gamma thalamotomy for movement
      disorders.
AB  - A theoretical and practical process from microrecording-guided thalamotomy to
      gamma knife thalamotomy was briefly reviewed. Based on our own experiences of
      selective thalamotomy with microrecording, we are trying to apply gamma knife to
      the treatment of movement disorders. An important technical problem is how to
      determine the exact thalamic target. At first we refer to the posterior
      commissure and coordinate of the standard atlas for approximately determining the
      lateral part of the ventral intermediate nucleus. Then the point is further
      corrected by anatomical landmark (45% of the thalamic length) to compensate the
      individual difference. A final lesion is made by gamma knife using a 4-mm
      collimator, 130 Gy in 1 shot. The average delay of clinical improvement is about
      6 months after irradiation. Thus far the results are satisfactory, being 80-85%
      successful without any noticeable complications. Only 3 days of hospitalization
      with minimal invasion could be a big advantage for the patient. Further technical
      progress may improve the clinical results in the future.

PMID- 16905880
TI  - Direct effect of subthalamic nucleus stimulation on levodopa-induced peak-dose
      dyskinesia in patients with Parkinson's disease.
AB  - We examined the direct effect of deep brain stimulation of the subthalamic
      nucleus (STN-DBS) on levodopa-induced peak-dose dyskinesia in 45 patients with
      Parkinson's disease (PD) without reducing the levodopa dosage during the early
      period after surgery. In 8 patients (18%), the dyskinesia was quickly attenuated
      by bipolar stimulation in an experimental trial (5 min) with the contacts placed
      within the area above the STN. In contrast, bipolar stimulation using contacts
      placed within the STN itself tended to provoke or exacerbate the dyskinesia,
      indicating that dyskinesia could be inhibited by stimulation of the areas above
      the STN rather than the STN itself. In an attempt to control the cardinal
      symptoms of PD and dyskinesia at the same time, we employed bipolar stimulation
      with a longer interpolar distance as a therapeutic procedure (2 weeks), using
      contacts within the STN as a cathode and contacts within the area above the STN
      as an anode. Bilateral STN-DBS significantly attenuated the dyskinesia as
      evaluated by the dyskinesia severity rating scale (p < 0.05). In 24 patients
      (53%), almost complete control of the dyskinesia was observed. The contacts used
      as an anode in these patients were located more dorsally compared to those of the
      remaining patients, suggesting again that the dyskinesia was inhibited by
      stimulation of the areas above the STN rather than the STN itself. In the area
      above the STN, pallidothalamic, pallidosubthalamic and subthalamopallidal fibers
      are densely distributed. It appears that stimulation of these fibers may cause
      effects similar to thalamic or pallidal DBS and therefore inhibit peak-dose
      dyskinesia. Bipolar STN-DBS with contacts placed within the area above the STN as
      an anode appears to represent a useful option for controlling both the cardinal
      symptoms of PD and peak-dose dyskinesia at the same time.

PMID- 16905881
TI  - Thalamic sensory relay nucleus stimulation for the treatment of peripheral
      deafferentation pain.
AB  - We applied chronic deep brain stimulation (DBS) of the thalamic nucleus ventralis
      caudalis (Vc) for the treatment of peripheral deafferentation pain. The subjects
      included 11 cases of phantom limb pain and 7 of root or nerve injury pain without
      phantom sensation. In the phantom limb pain patients, the spike density markedly
      increased in the same area of the Vc where microstimulation induced paresthesia
      in the part with phantom sensation. Reorganization of the receptive field
      representation within the Vc was also demonstrated by microrecording and
      microstimulation. In the root or nerve injury pain patients with severe allodynia
      and without phantom sensation, oscillating neural hyperactivity appeared when the
      allodynia was induced during single-cell recording in the Vc. In both groups
      stimulation of these areas with the DBS electrode was useful for achieving pain
      reduction. Inhibition of spinothalamic tract neurons, restoration of the original
      receptive field representation and modulation of thalamocortical rhythmic
      oscillations are proposed to play important roles in a possible mechanism of Vc
      DBS for the treatment of deafferentation pain.

PMID- 16905882
TI  - The impact of arteriovenous malformation radiosurgery on the brain: From
      morphology and perfusion to neurocognition.
AB  - The therapeutic aims of brain arteriovenous malformation (AVM) radiosurgery are
      multiple. Protecting patients from rebleeding is the prime goal. Among the
      others, hemodynamics, perfusion and neurocognition recovery are interesting and
      important. Anatomically AVM contains an abnormal cluster of vascular networks
      (nidus) between arteries and veins. Hemodynamically the nidus contains a low
      resistance and causes high-flow transnidal shunts between both sides of the
      nidus. The shunts cause hypotension in the neighboring arteries and diversion of
      blood from the adjacent brain tissues. The diversion disturbs brain hemodynamics.
      Radiosurgery, by eliminating the nidus, reconstitutes normal brain hemodynamics.
      From the early stage after radiosurgery, the abnormal transnidal flows gradually
      decrease, and the adjacent hemodynamics recovers toward normal. For
      nonhemorrhagic AVM, improvement of seizure control and stable or improved
      neurological status are observed clinically. The radiosurgical effects are also
      reflected in the recovery of metabolism in the adjacent brain and neurocognitive
      function paralleling the hemodynamic normalization. Morphological cure of AVM and
      the associated recovery of brain hemodynamics, metabolism and neurocognitive
      function form the therapeutic rationale of AVM radiosurgery.

PMID- 16905883
TI  - Relationship of stimulation site location within the subthalamic nucleus region
      to clinical effects on parkinsonian symptoms.
AB  - OBJECTIVE: To determine the relationship of the stimulation site in the
      subthalamic region to the clinical effects on parkinsonian symptoms, the
      monopolar stimulation of 4 electrode contacts and the resulting effects on
      parkinsonian symptoms were evaluated. METHODS: Seventeen consecutive patients (3
      males and 14 females) were enrolled in the study. The patients were evaluated
      while in a nonmedicated state, and 10-20 min after switching on the pulse
      generator the effects of stimulation were assessed using separate-subset Unified
      Parkinson's Disease Rating Scale scores. RESULTS: The relationship between the
      site stimulated and the percent improvement was analyzed using polynomial
      regression. Rigidity (p = 0.0004, R2 = 0.15), akinesia (p = 0.02, R2 = 0.07) and
      total score (p = 0.009, R2 = 0.089) well fit to second-order polynomial
      regression and showed the greatest improvement after stimulation at 0-1 mm below
      the horizontal anterior-posterior commissure (AC-PC) plane. Tremor (p = 0.24, R2
      = 0.18) and gait (p = 0.36, R2 = 0.001) had a weak relation to the site
      stimulated, but stimulation at the sites 0-1 mm below the AC-PC plane also
      produced greater improvement than stimulation at more ventral or dorsal sites.
      The percent improvement of the posture (p = 0.92, R2 = 0.002) had no relation to
      the site stimulated. The dorsal border of the subthalamic nucleus was located 0.6
      +/- 1.2 mm (n = 27) below the AC-PC plane and the most effective electrode
      contact 1.2 +/- 1.3 mm (n = 27) below it. CONCLUSIONS: Stimulation around the
      dorsal border of the subthalamic nucleus, close to the AC-PC plane, produces
      greater improvement of parkinsonian symptoms than stimulation at more ventral or
      dorsal sites.

PMID- 16905884
TI  - Muscle strength and vitamin D in older people.

PMID- 16905886
TI  - Posturography and risk of recurrent falls in healthy non-institutionalized
      persons aged over 65.
AB  - BACKGROUND: A poor postural stability in older people is associated with an
      increased risk of falling. The posturographic tool has widely been used to assess
      balance control; however, its value in predicting falls remains unclear.
      OBJECTIVE: The purpose of this prospective study was to determine the predictive
      value of posturography in the estimation of the risk of recurrent falls,
      including a comparison with standard clinical balance tests, in healthy non
      institutionalized persons aged over 65. METHODS: Two hundred and six healthy non
      institutionalized volunteers aged over 65 were tested. Postural control was
      evaluated by posturographic tests, performed on static, dynamic and dynamized
      platforms (static test, slow dynamic test and Sensory Organization Test [SOT])
      and clinical balance tests (Timed 'Up & Go' test, One-Leg Balance, Sit-to-Stand
      test). Subsequent falls were monitored prospectively with self-questionnaire sent
      every 4 months for a period of 16 months after the balance testing. Subjects were
      classified prospectively in three groups of Non-Fallers (0 fall), Single-Fallers
      (1 fall) and Multi-Fallers (more than 2 falls). RESULTS: Loss of balance during
      the last trial of the SOT sensory conflicting condition, when visual and
      somatosensory inputs were distorted, was the best factor to predict the risk of
      recurrent falls (OR = 3.6, 95% CI = 1.3-10.11). Multi-Fallers showed no postural
      adaptation during the repetitive trials of this sensory condition, contrary to
      Non-Fallers and Single-Fallers. The Multi-Fallers showed significantly more sway
      when visual inputs were occluded. The clinical balance tests, the static test and
      the slow dynamic test revealed no significant differences between the groups.
      CONCLUSION: In a sample of non-institutionalized older persons aged over 65,
      posturographic evaluation by the SOT, especially with repetition of the same task
      in sensory conflicting condition, compared to the clinical tests and the static
      and dynamic posturographic test, appears to be a more sensitive tool to identify
      those at high-risk of recurrent falls.

PMID- 16905885
TI  - Acute abdominal pain among elderly patients.
AB  - BACKGROUND: Diagnosis of acute abdominal pain in older persons is a challenge,
      with the age-related increase in concurrent diseases. In most western countries
      the number of elderly people is constantly rising, which means that an increasing
      proportion of patients admitted for abdominal pain at the emergency department
      are elderly. OBJECTIVE: To characterize differences in clinical presentation and
      diagnostic accuracy between younger and more elderly patients with acute
      abdominal pain. METHODS: Patients admitted to Mora Hospital with abdominal pain
      of up to seven days' duration were registered according to a detailed schedule.
      From 1st February 1997 to 1st June 2000, 557 patients aged 65-79 years and 274
      patients aged > or = 80 years were registered. Patients aged 20-64 years (n =
      1,458) served as a control group. RESULTS: A specific diagnosis, i.e. other than
      'nonspecific abdominal pain', was established in 76 and 78% of the patients aged
      65-79 and > or = 80 years respectively, and in 64% of those aged 20-64 (p <
      0.001). Pain duration before admission increased with age (p < 0.003), as did
      frequency and duration of hospitalization (p < 0.0001). Hospital stay increased
      from 170 days per 100 emergency admissions in the control group to 320 and 458
      days in the younger and older study groups, respectively. At the emergency
      department, older patients were more often misdiagnosed than control patients (52
      vs. 45%; p = 0.002). At discharge the diagnosis was more accurate in the control
      group (86 vs. 77%; p < 0.0001). Hospital mortality was higher among older
      patients (23/831 vs. 2/1,458; p < 0.001). The admission-to-surgery interval was
      increased (1.8 vs. 0.9 days, p < 0.0001) in patients > or = 65 years. Rebound
      tenderness (p < 0.0001), local rigidity (p = 0.003) and rectal tenderness (p =
      0.004) were less common in the older than in the control patients with
      peritonitis. In patients > or = 65 years, C-reactive protein did not differ
      between patients operated on and those not, contrary to the finding in patients <
      65 years (p < 0.0001). CONCLUSION: Both the preliminary diagnosis at the
      emergency department and the discharge diagnosis were less reliable in elderly
      than in younger patients. Elderly patients more often had specific organic
      disease and arrived at the emergency department after a longer history of
      abdominal pain compared to younger patients.

PMID- 16905887
TI  - Mobility limitations and cognitive deficits as predictors of institutionalization
      among community-dwelling older people.
AB  - PURPOSE: Mobility limitations and cognitive disorders have often been observed as
      risks for institutionalization. However, their combined effects on risk of
      institutionalization among initially community-dwelling older people have been
      less well reported. DESIGN: A prospective cohort study with 10-year surveillance
      on institutionalization. SUBJECTS: Study population (n = 476) consisted of 75-
      and 80-year-old people who were community-dwelling, had not been diagnosed with
      dementia, and participated in tests on walking speed and cognitive capacity at a
      research centre. MEASURES: Cognitive capacity was measured with three validated
      psychometric tests that were from the Wechsler Adult Intelligence Scale, Wechsler
      Memory Scale and Schaie-Thurstone Adult Mental Abilities Test. Mobility was
      measured with walking speed over a 10-m distance. Exclusive distribution based
      study groups were formed with cut-offs at the lowest third as follows: no
      limitation, solely mobility limitation, solely cognitive deficits, and combined
      mobility limitation and cognitive deficits. Cox proportional hazards model was
      used to determine the relative risks of institutionalization for the study
      groups. RESULTS: Eleven percent of the participants were institutionalized during
      the 10-year surveillance. The risk for institutionalization was 4.9 times greater
      (95% confidence interval: 2.1-11.2) for those who had co-existing mobility
      limitations and cognitive deficits than for those with no limitations.
      CONCLUSIONS: The findings show that the accumulation of limitations in physical
      and cognitive performance substantially decreases the possibility for a person
      remaining at home. This might be due to a decreased reserve capacity and
      ineffective compensatory strategies. Therefore, interventions targeted to improve
      even one limitation, or prevent accumulation of these risk factors, could
      significantly reduce the risk of institutionalization.

PMID- 16905888
TI  - Psychological and physical activity training for older persons: who does not
      attend?
AB  - BACKGROUND: Interventions to promote successful aging include psychological and
      physical activity programs. Identification of determinants of attendance of older
      persons may be useful to develop strategies to improve attendance. For physical
      activity programs determinants of attendance have been investigated extensively.
      For psychological programs hardly any knowledge is available. Determinants of
      attendance at psychological and physical activity programs have never been
      investigated simultaneously. OBJECTIVE: To identify demographic, physical and
      psychological determinants of attendance of older subjects following multifaceted
      psychological training - aimed at promoting active social participation - and
      physical activity training and to compare the variation of these determinants
      between the two training programs. METHOD: 118 subjects aged 65-92 years were
      randomized over psychological and physical activity training. Determinants of
      attendance were obtained at pretest with questionnaires and performance-based
      tests. RESULTS: Mean attendance was 62%. Attendance was not related to type of
      program. Having chronic diseases facilitated attendance in the psychological
      training group and limited attendance in the physical activity training group.
      Low and high levels of Activities of Daily Living performance (ADLs) and walking
      endurance were related to a high attendance in the psychological training group.
      A low level of activities of daily living (ADL) and a low walking endurance were
      related to a low attendance in the physical activity training group. For both
      training groups, persons living with a partner had higher attendance rates than
      persons living alone, and persons with a low level of anxiety had higher
      attendance rates than persons with a moderate or a high level of anxiety.
      CONCLUSION: Psychological training may be more suitable for frail older persons
      with chronic diseases, low ADL levels and low walking endurance than physical
      activity training, and may help to prepare such persons for physical activity.

PMID- 16905889
TI  - Quality of life: scaling with Maslow's need hierarchy.

PMID- 16905890
TI  - [Early results of medial opening wedge osteotomy in varus gonarthrosis].
AB  - OBJECTIVES: We evaluated the efficacy and short-term results of medial opening
      wedge high tibial osteotomy with the use of a Puddu plate in patients with medial
      compartment gonarthrosis. METHODS: The study included 15 knees of 12 female
      patients (mean age 50.6 years; range 45 to 63 years) who were treated with medial
      opening wedge high tibial osteotomy for varus knees with medial compartment
      gonarthrosis. The osteotomy sites were fixed with a Puddu plate followed by
      allograft application. The mean follow-up period was 30.7 months (range 19 to 40
      months). RESULTS: The mean consolidation time was 7.1 weeks (range 6 to 9 weeks).
      The mean preoperative and postoperative Lysholm scores were 54.1 (range 30 to 60)
      and 82 (range 67 to 95), respectively. The mean preoperative femorotibial angle
      was 3.5 degrees in varus malalignment (range 3 degrees valgus to 9 degrees
      varus). It was 7.3 degrees valgus postoperatively. The mean correction of the
      mechanical axis was 10.7 degrees , with no loss of correction during the follow
      up period. No adverse effects were observed associated with allograft use. The
      lateral cortex was broken in one patient (6.7%) who was then treated with an
      Ilizarov external fixator due to pseudoarthrosis. All but this patient were
      satisfied with the treatment. CONCLUSION: Compared with other osteotomy models,
      medial opening wedge osteotomy with the use of a Puddu plate offers advantages in
      terms of ease of application and maintenance of correction in the early follow-up
      period. With allograft application, consolidation is obtained without interfering
      with the rehabilitation period.

PMID- 16905891
TI  - [Psychological evaluation of patients with benign musculoskeletal system tumors].
AB  - OBJECTIVES: This study was designed to determine to what extent psychological
      status was affected by sociodemographic characteristics and by being informed
      about the diagnosis in patients with benign musculoskeletal tumors. METHODS: The
      study included 112 male patients (mean age 23.8 years; range 20 to 35 years) who
      were hospitalized for benign tumors of the musculoskeletal system. A
      questionnaire was administered to all the patients concerning their
      sociodemographic characteristics and the status of their knowledge about the
      diagnosis. Psychological status was assessed by the Hamilton Depression
      Evaluation Scale. RESULTS: The depression level was not correlated with the
      localization (upper or lower extremity) of the musculoskeletal system tumor, the
      marital status of the patient, and the presence or absence of knowledge of the
      patient about the diagnosis (p>0.05). Educational status was the only factor that
      was found to be in correlation with the depression level (p<0.05). CONCLUSION:
      Lack of correlation between sociodemographic characteristics and the
      psychological status suggests that informing the patients with special attention
      to their physical and psychological integrity may contribute positively to the
      patients' psychiatric status.

PMID- 16905892
TI  - [Heterotopic ossification after total knee arthroplasty].
AB  - OBJECTIVES: The purpose of this study was to determine the incidence, time to
      development and clinical presentation of heterotopic ossification (HO) after
      total knee arthroplasty (TKA). METHODS: We retrospectively reviewed consecutive
      radiographs of 226 knees that were obtained at the end of sixth week, third,
      sixth, and twelfth months following TKA. The radiographic diagnosis of HO was
      based on the comparison of pre- and postoperative serial radiographs. Grading of
      HO was made according to the classification of Figgie et al. The clinical and
      radiographic course of HO and possible predisposing factors were investigated. No
      pharmacological prophylaxis was used other than mechanical measures to prevent
      deep vein thrombosis. RESULTS: Heterotopic ossification was detected only in two
      knees (0.9%) at the sixth month evaluation of lateral radiographs. It was grade 1
      in both knees and localized at the supracondylar area of the distal femur. Both
      patients had primary osteoarthritis. There were no complaints except for mild
      nonspecific pain around the knee while standing. In both cases, HO underwent
      spontaneous improvement and disappeared on the twelfth month radiographs.
      CONCLUSION: Compared with previous studies, the incidence of HO after TKA was
      quite low and this could be attributed to the lack of pharmacological
      thromboprophylaxis. Delayed appearance of HO in two patients suggests that TKA
      cases be monitored for a longer period for HO development.

PMID- 16905893
TI  - [Image-guided minimal invasive surgical resection of osteoid osteomas of the long
      bones].
AB  - OBJECTIVES: In this prospective study, we evaluated the efficiency of image
      guided minimal invasive surgical resection of osteoid osteomas of the long bones.
      METHODS: Fourteen patients (11 males, 3 females; mean age 13 years; range 4 to 22
      years) with osteoid osteoma of the long bones underwent image-guided minimal
      invasive intralesional extended curettage. Preoperatively, all the patients were
      evaluated by plain radiographs, computed tomography (CT), bone scintigraphy, and
      magnetic resonance imaging (MRI). Localization of the nidus was determined by
      measurements on thin-section (1-1.5 mm) CT scans and MR images and complete
      excision of the nidus was performed by image-guided minimal invasive technique.
      All the patients were evaluated by visual analog scale or faces pain scale to
      determine pain levels before and after surgery. The mean follow-up period was 17
      months (range 13 to 31 months). RESULTS: The mean visual analog scale scores were
      7.9+/-1.2 (severe pain) and 0.3+/-0.6 (no pain) before and after surgery,
      respectively (p<0.05). Bone grafting or internal fixation were not required
      during operations. No perioperative or postoperative complications or recurrences
      were encountered. Early mobilization was possible in all the patients. At the
      final follow-ups, all the patients were asymptomatic and had full functional use
      of their operated extremities. CONCLUSION: Image-guided minimal invasive surgery
      is effective in the local control of osteoid osteomas affecting the long bones
      and causes less morbidity. This technique also provides a good identification of
      the nidus intraoperatively.

PMID- 16905894
TI  - [Surgical treatment of isolated post-traumatic subscapularis tendon ruptures].
AB  - OBJECTIVES: We retrospectively evaluated the functional results of patients who
      were treated surgically for post-traumatic isolated subscapularis tendon
      ruptures. METHODS: The study included six patients (5 males, 1 female; mean age
      63.3 years; range 53 to 70 years) who were operated on for isolated post
      traumatic subscapularis ruptures. The mean interval between the development of
      symptoms due to trauma and operation was 4.3 months (range 1 to 9 months).
      Mechanism of injury, complaints, clinical findings, imaging methods, arthroscopic
      and surgical findings, repair techniques, and postoperative follow-up data were
      assessed. Evaluations were based on physical assessment, radiographic
      examination, and the UCLA (University of California at Los Angeles) score. The
      mean follow-up was 29.6 months (range 13 to 53 months). RESULTS: The mean UCLA
      score was 11.3 (range 9 to 14) preoperatively. It increased to 25.8 (range 12 to
      31) postoperatively (p<0.05). The results were good in four patients, fair in one
      patient, and poor in one patient. Magnetic resonance images obtained in five
      patients at the final follow-up showed total rupture in the patient with poor
      outcome, partial rupture in the patient with fair outcome, and maintenance of
      tendon integrity in the remaining patients. CONCLUSION: A careful clinical
      examination may enable the diagnosis of subscapularis tendon ruptures. Magnetic
      resonance imaging may provide additional information. In most patients, the
      repair of the tendon is possible by proper protection of the axillary nerve and
      appropriate mobilization.

PMID- 16905895
TI  - [Triple arthrodesis in rigid foot deformities and the effect of internal fixation
      on clinical and radiographic results].
AB  - OBJECTIVES: We evaluated the results of triple arthrodesis in rigid foot
      deformities and assessed the effect of internal fixation on clinical and
      radiographic results. METHODS: Thirty feet of 26 patients (12 females, 14 males;
      mean age 27 years; range 13 to 55 years) were treated with classic triple
      arthrodesis. Ten patients (12 feet) underwent temporary internal fixation with
      one or more Kirschner wires. Clinical evaluations were made with the use of both
      AOFAS (American Orthopaedic Foot and Ankle Society) and Angus-Cowell ankle
      hindfoot scoring systems. Anteroposterior and lateral talocalcaneal and talus
      first metatarsal angles were used as radiographic parameters. The mean follow-up
      period was 80.3 months (range 30 to 140 months). RESULTS: The mean AOFAS score
      increased from a preoperative 39.3 (range 16 to 59) to postoperative 90.8 (range
      71 to 94). According to the Angus-Cowell criteria, the results were good in 19
      feet (63.3%), fair in eight feet (26.7%), and poor in three feet (10%). Clinical
      improvement was statistically significant according to both scoring systems
      (p<0.05). Radiographically, all the angular values were within normal limits both
      in the early postoperative period and at the last follow-up (p<0.05).
      Pseudoarthrosis was detected in four feet (13.3%) and degeneration of the ankle
      and naviculocuneiform joints was detected in 12 feet (40%) and 17 feet (56.7%),
      respectively. Internal fixation had no significant effect on pseudoarthrosis,
      residual or recurrent deformity, and the degree of degeneration (p>0.05).
      CONCLUSION: Triple arthrodesis is a good alternative for functional and cosmetic
      improvement in foot deformities. Although internal fixation seems to have no
      significant effect, the use of a temporary fixation material may contribute to
      maintenance of reduction and surface contact.

PMID- 16905896
TI  - [Primary surgical repair with the Krackow technique combined with plantaris
      tendon augmentation in the treatment of acute Achilles tendon ruptures].
AB  - OBJECTIVES: We evaluated the long-term results of acute Achilles tendon ruptures
      treated with primary end-to-end repair with the Krackow technique combined with
      augmentation using the plantaris tendon. METHODS: Thirty-six patients (31 males,
      5 females; mean age 34 years; range 21 to 42 years) underwent primary surgical
      repair for acute Achilles tendon ruptures. Most of the patients (31/36) were
      involved in regular sportive activities. Surgery included end-to-end repair with
      the Krackow technique (locking-loop) combined with plantaris tendon augmentation.
      All the patients received a standardized progressive postoperative rehabilitation
      program. The results were evaluated with respect to time to return to work and
      preinjury activity levels and by a scoring system covering objective and
      subjective parameters. The mean follow-up was 54 months (range 28 to 78 months).
      RESULTS: At surgery, 34 patients (94.4%) and two patients (5.6%) were found to
      have complete and partial ruptures, respectively. The mean operation time was 50
      minutes (range 40 to 70 minutes). The patients returned to work after a mean of
      eight weeks (range 6 to 9 weeks) and to preinjury sportive activities after a
      mean of 17 weeks (range 14 to 20 weeks). The overall mean scoring was good (88
      out of 100) at the end of a year follow-up. Early or late complications included
      superficial wound infections in five patients and partial rupture recurrence in
      one patient. CONCLUSION: Our results showed that the Krackow technique combined
      with plantaris tendon augmentation and a rehabilitation protocol aiming early
      motion enabled physiological tendon healing.

PMID- 16905897
TI  - [Klippel-Feil syndrome and associated congenital abnormalities: evaluation of 23
      cases].
AB  - OBJECTIVES: The purpose of this study was to review adult patients with Klippel
      Feil syndrome. METHODS: The study included 23 male patients (mean age 20.5 years,
      range 19 to 27 years) with Klippel-Feil syndrome. Besides orthopedic clinical
      evaluation, all the patients were assessed by anteroposterior and lateral
      cervical flexion/extension and thoracolumbar radiographies, abdominal
      ultrasonography, and were subjected to systemic examinations to detect any
      urological, cardiological, otorhinolaryngological, neurological, and psychiatric
      findings. Temporal computed tomography was performed in seven patients, and
      cervical magnetic resonance imaging in three patients. RESULTS: Scoliosis, fusion
      of the cervical vertebrae (between 2-5 vertebrae), low hairline and short neck
      were found in all the cases. Lumbar fusion was detected in one patient. Other
      findings included renal agenesis (n=1), different types of hearing loss (n=9),
      cardiac pathologies (n=5), epilepsy (n=1), and marked (n=1) or mild (n=1) mirror
      movements. CONCLUSION: Patients with Klippel-Feil syndrome should be assessed for
      associated systemic abnormalities besides cervical fusion.

PMID- 16905898
TI  - [Blumensaat line and patellar height].
AB  - OBJECTIVES: We investigated the agreement between the Blumensaat method and
      patellar height ratios and evaluated the reliability of the method in patellar
      height measurements. METHODS: We retrospectively evaluated 105 digital knee x
      rays of 77 patients (23 males, 54 females; mean age 32 years; range 21 to 62
      years), whose radiographs were obtained at 30 degrees of knee flexion. Patellar
      heights were measured with the use of the Blumensaat, Insall-Salvati, modified
      Insall-Salvati, and Blackburne-Peel methods. Patellar height was also evaluated
      after standardization of the angle between the femoral shaft and the Blumensaat's
      line (corrected Blumensaat method). Agreement and correlations were sought
      between the qualitative and quantitative results of the methods, respectively.
      RESULTS: When the qualitative results were considered, agreement of the
      Blumensaat method was very weak with the Insall-Salvati, modified Insall-Salvati,
      and Blackburne-Peel methods (kappa coefficients: 0.21, -0.14, and 0.12,
      respectively). The corrected Blumensaat method also had a very weak agreement
      with the other indices (kappa coefficients: 0.27, -0.11, and 0.13, respectively).
      Correlation analyses of the quantitative results showed very weak to moderate
      correlations between the methods used. The Blumensaat method was relatively well
      correlated with the modified Insall-Salvati method (r=0.514, p<0.05).
      Correlations were weak to moderate between the patellar height indices, the
      highest correlation being between the modified Insall-Salvati and Blackburne-Peel
      methods (r=0.557, p<0.05). CONCLUSION: The results of the patellar height
      measurements obtained by the Blumensaat method do not agree with widely used
      patellar height indices.

PMID- 16905900
TI  - [Posterior interosseous nerve palsy due to lipoma].
AB  - A 45-year-old male patient presented with paralysis of slow onset in the right
      forearm and hand muscles. Electromyographic assessment revealed severe
      denervation in the muscles innerved by the posterior interosseous nerve. Magnetic
      resonance imaging demonstrated a tumoral mass compressing the nerve. The patient
      underwent surgical excision with an initial diagnosis of lipoma. Surgical
      exploration and a biopsy confirmed the diagnosis. Active wrist movements and
      digital extension were possible after three weeks and the patient resumed full
      strength six weeks after the operation.

PMID- 16905899
TI  - [Comparison of three fixation methods in transverse fractures of the patella in a
      calf model].
AB  - OBJECTIVES: We evaluated the strength of three different fixation methods against
      distraction forces in a transverse fracture model of calf patellae. METHODS:
      Thirty calf patellae were randomly divided into three groups equal in number.
      Transverse fractures were induced at the same localization in all the samples.
      The fractures were fixed with a modified anterior tension band technique, Acutrak
      4/5 screws, and a combination of Acutrak 4/5 screws and tension band technique in
      three groups, respectively. Following fixation, each patella was mounted in a
      compression-distraction testing machine from the quadriceps and patellar tendons
      on each side of the patella, and equal distraction forces were applied to each
      patella. The average load to failure at the fracture site was calculated and the
      results were compared with the Friedman test. RESULTS: The mean failure loads
      were significantly different in three groups, being 288.8+/-40.1 newton (N),
      878.5+/-68.6 N, and 938.6+/-38.8 N, respectively (p<0.001). The most efficient
      stabilization was obtained in the third group in which Acutrak 4/5 screws and the
      tension band application were used in combination, while the modified anterior
      tension band technique alone was found to be the weakest fixation technique.
      CONCLUSION: Our results showed that Acutrak 4/5 screws enabled a rigid fixation
      in the surgical treatment of patellar fractures.

PMID- 16905901
TI  - [Treatment algorithm in synovial tuberculosis of the hand and wrist: a report of
      three cases].
AB  - Three patients with synovial tuberculosis are presented. Involvement was in the
      hand in one patient, and in the wrist in two patients. None of the patients had
      pulmonary tuberculosis or a family history of tuberculosis. Tuberculosis
      treatment was initiated only after histologic verification. The cultures remained
      negative. The patients received a 12-month course of multidrug chemotherapy for
      tuberculosis, resulting in symptomatic improvement and healing. There were no
      recurrences during a follow-up period of 16 to 26 months. Our clinical
      observations showed that tuberculosis tenosynovitis benefited well from
      antituberculosis chemotherapy.

PMID- 16905903
TI  - [Notice of retraction: Ekin A et al. Multidirectional shoulder instability and
      open surgical procedures. Acta Orthop Traumatol Turc 2005;39 Suppl. 1:83-89].

PMID- 16905902
TI  - [Traumatic obturator hip dislocation in a five-year-old boy: open reduction after
      a six-week delay in diagnosis].
AB  - Hip dislocations are relatively uncommon in children, they may occur before five
      years of age as a result of seemingly trivial trauma. A 5-year-old boy was
      admitted with knee pain six weeks after a fall from bed. Physical examination
      showed obturator dislocation of the left hip. Owing to the late presentation and
      without attempting closed reduction, the patient was treated with open reduction
      and capsulorrhaphy. At the end of a year follow-up, the patient had no complaints
      and no functional restriction.

PMID- 16905904
TI  - [Intraoperative planning and inset principles of fibula osteoseptocutaneous flap
      in compound or composite oromandibular defect reconstruction].
AB  - OBJECTIVES: The use of free fibular osteocutaneous flap was evaluated in the
      reconstruction of compound and composite mandibular defects. PATIENTS AND
      METHODS: The study included 30 patients (27 males, 3 females, mean age 52.6
      years; range 42 to 66 years) who received free osteoseptocutaneous fibular flap
      for the reconstruction of compound or composite oromandibular defects following
      surgical tumor ablation. Five patients with extensive skin defects accompanying
      lateral mandible and oral defects also received free anterolateral thigh
      perforator flap. Other patients were treated with conventional fibular
      osteocutaneous flap or its chimeric form. The mean follow-up period was 19.4
      months (range 8 to 38 months). RESULTS: With the applied technique, a successful
      functional and aesthetic restoration was achieved without total flap failure and
      with minimal donor site morbidity. Infection and fascial abscess encountered in
      one patient were treated with debridement and antibiotic therapy. In one patient
      who developed osteonecrosis in the neomandibula, the plate was removed and
      debridement was performed in the 13th month. CONCLUSION: By appropriate flap
      planning and placement, reconstruction of large oromandibular tumors with
      osteocutaneous fibular flaps provides successful functional and aesthetic
      restoration.

PMID- 16905905
TI  - [The use of serum and nasal eosinophilic cationic protein in the evaluation of
      the effectiveness of immunotherapy in patients with allergic rhinitis].
AB  - OBJECTIVES: We investigated the use of eosinophilic cationic protein (ECP) as an
      indicator of clinical efficiency of specific immunotherapy (SIT) in patients with
      allergic rhinitis sensitive to house dust mites. PATIENTS AND METHODS: Specific
      immunotherapy was administered to 49 patients (20 males, 29 females; mean age
      34.2 years; range 16 to 66 years) with perennial allergic rhinitis. Nasal
      secretion and serum ECP levels were measured before, at the 6th month of, and two
      years after completion of, treatment. Comparisons were made within the patient
      group and with a control group of 16 healthy subjects (10 males, 6 females; mean
      age 23 years; range 17 to 26 years). RESULTS: Pretreatment nasal ECP levels were
      significantly higher than those found after the treatment (p<0.001). Nasal ECP
      levels measured before SIT were significantly different from those of the control
      group (p<0.05). However, serum ECP levels did not differ significantly between
      the two groups (p>0.05). Serum ECP levels in the patient group tended to decrease
      with treatment (p>0.05). CONCLUSION: We conclude that, in addition to the
      symptoms and clinical findings, nasal ECP measurement may be a reliable and
      suitable laboratory method to monitor and evaluate the effectiveness of
      treatment.

PMID- 16905906
TI  - [Transcanal butterfly cartilage tympanoplasty].
AB  - OBJECTIVES: This study evaluated the long-term results of transcanal butterfly
      cartilage tympanoplasty technique in adult patients. PATIENTS AND METHODS:
      Transcanal butterfly cartilage tympanoplasty was performed in 11 adult patients
      (7 males, 4 females; mean age 30 years; range 21 to 45 years) with chronic otitis
      media. The operations were performed under general or local anesthesia.
      Perforation diameters ranged from 2 to 6 mm. The mean follow-up period was 9.5
      months. RESULTS: At the end of the follow-up period, perforations closed in 10
      patients (90.9%). In one patient, reperforation occurred in the second month. The
      mean preoperative and postoperative air-bone gaps obtained in 10 patients were 18
      dB and 6.5 dB, respectively. CONCLUSION: Butterfly cartilage tympanoplasty
      technique was very effective to close central, small tympanic membrane
      perforations associated with minimal hearing loss.

PMID- 16905907
TI  - [Microorganisms isolated from middle ear cultures and their antibacterial
      susceptibility in patients with chronic suppurative otitis media].
AB  - OBJECTIVES: This study sought to determine causative microorganisms of chronic
      suppurative otitis media and their antibacterial susceptibility. PATIENTS AND
      METHODS: Bacteriologic results of middle ear swabs, agent microorganisms, and
      their susceptibility to antibiotics were evaluated in 70 patients (65 males, 5
      females; mean age 21.1+/-1.3 years; range 19 to 25 years) with chronic
      suppurative otitis media. RESULTS: No bacteria were isolated in 14% of the
      patients. Of 60 patients in whom bacteria were isolated, the most common bacteria
      was Pseudomonas aeruginosa (23%), followed by Staphylococcus aureus (18%), and
      Proteus spp. (17%). P. aeruginosa strains were susceptible to ceftazidime and
      imipenem (100%), ciprofloxacin (92%), and amikacin and gentamycin (85%); S.
      aureus strains were susceptible to methicillin and vancomycin (100%),
      ciprofloxacin (91%), sulbactam-ampicillin (73%), and gentamycin and trimethoprim
      sulfamethoxazole (63%). Proteus strains were susceptible to ciprofloxacin (100%),
      ceftazidime (90%), and imipenem and gentamycin (70%). CONCLUSION: Appropriate
      knowledge of antibacterial susceptibility of microorganisms will contribute to
      rational antibiotic usage and the success of treatment for chronic suppurative
      otitis media.

PMID- 16905908
TI  - [Assessment of patients with sudden hearing loss by transcranial Doppler
      ultrasonography].
AB  - OBJECTIVES: We evaluated the utility of transcranial Doppler ultrasonography in
      determining the vascular pathology in patients with sudden hearing loss. PATIENTS
      AND METHODS: The study included 13 patients (11 males, 2 females; mean age 46.6+/
      17.7 years; range 18 to 66 years) with a diagnosis of sudden hearing loss.
      Patients having chronic otitis media or other middle ear diseases or a history of
      surgery in the affected ear were excluded. All the patients were evaluated by
      pure-tone audiometry, impedance audiometry, transient evoked otoacoustic
      emissions, auditory brainstem responses, and transcranial Doppler
      ultrasonography. The results were compared with those of a control group of 19
      age- and sex-matched healthy subjects (12 males, 7 females; mean age 46.8+/-6.9
      years; range 33 to 58 years) who did not have any ear disease or a history of
      ototoxic drug intake or working in a noisy environment, and no pathology on
      otoscopic and audiometric examinations. RESULTS: Compared to the normal ear, the
      mean blood flow and systolic flow velocities of the vertebral artery were
      significantly decreased, and the mean pulsatile index was significantly increased
      on the affected side. The mean flow velocity of the basilar artery in the patient
      group was lower than that found in the control group. CONCLUSION: Transcranial
      Doppler ultrasonography can be used for the evaluation of vascular involvement of
      the vertebral and basilar arteries in patients with sudden sensorineural hearing
      loss.

PMID- 16905909
TI  - [An etiological study in a school for the deaf and radiological findings].
AB  - OBJECTIVES: The causes of sensorineural hearing loss were assessed in a
      population of students in a school for the deaf. PATIENTS AND METHODS: Ninety-one
      students (34 girls, 57 boys; mean age 10.6 years; range 7 to 20 years) from a
      school for the deaf were evaluated together with their family tree.
      Otolaryngologic, ophthalmologic, and systemic physical examinations and
      audiologic and radiologic investigations were performed. RESULTS: Sensorineural
      hearing loss was of genetic origin in 32.9% of the students. No etiologic factor
      could be determined in 31.9% of the cases. Infectious diseases (38.3%) and
      consanguinity (26.3%) were found as the most common etiologic factors in
      nongenetic and genetic sensorineural hearing losses, respectively. CONCLUSION:
      Sensorineural hearing losses due to infectious diseases and consanguineous
      marriages are preventable conditions. The incidence of sensorineural hearing loss
      will decline if these two conditions are controlled.

PMID- 16905910
TI  - [Psychiatric disorder profile in patients with chronic pharyngitis].
AB  - OBJECTIVES: We investigated the psychopathological condition of patients with
      chronic pharyngitis. PATIENTS AND METHODS: The study included 27 patients (23
      females, 4 males; mean age 41.7+/-10.4 years; range 21 to 63 years) who had
      persistent symptoms of chronic pharyngitis for more than six months, without any
      evidence for an acute infection on ENT examination and routine tests. Twenty
      seven healthy subjects (23 females, 4 males; mean age 41.8+/-11.9 years) without
      any symptoms of chronic pharyngitis and a previous diagnosis of a psychiatric
      disorder formed the control group. All the patients and controls were assessed by
      a psychiatrist with the use of the Structural Clinical Interview for DSM-IV
      Disorders (SCID). RESULTS: All the patients were diagnosed to have Axis I
      psychopathology. The most frequent pathologies were somatisation disorder (n=8,
      29.6%) and dysthymic disorder (n=8). Five individuals (15.6%) in the control
      group received psychiatric diagnoses. Psychiatric disorders were 6.4 times more
      frequent in the patient group (p=0.00, CI=2.86-14.31). No significant differences
      were observed between the patient and control groups with respect to educational
      and occupational levels (p=0.263 and p=0.362, respectively). Comparisons with
      respect to risk factors associated with chronic pharyngitis showed no significant
      differences between the two groups. CONCLUSION: We suggest that patients
      frequently presenting to ENT departments with repeated symptoms of chronic
      pharyngitis should also receive psychiatric assessment and support.

PMID- 16905911
TI  - [Non-Hodgkin's lymphoma of the parotid gland].
AB  - Most of the primary malignant lymphomas of the salivary glands originate from the
      parotid gland. We presented two patients who were admitted with a painless mass
      in the parotid region and diagnosed to have a lymphoma. Physical examination of a
      66-year-old male patient showed a relatively mobile, painless, and firm mass at
      the inferior aspect of the right parotid gland. Ultrasonography, computed
      tomography, and magnetic resonance imaging (MRI) were performed and a needle
      biopsy was obtained from the solid lesion extending from the right parotid
      superficial lobe to the medial deep lobe. Pathological examination revealed large
      B-cell lymphoma. The patient was treated according to the CHOP chemotherapy
      protocol. The second patient had undergone surgery for orbital lymphoma and
      received CHOP chemotherapy. On physical examination, there was a painless mass in
      the parotid cauda on the left and a subcutaneous lymph node, 0.5 x 1 cm in size,
      inferior to the parotid cauda. Computed tomography and MRI showed an irregularly
      contoured solid lesion, 2 x 1 cm in size, in the posteroinferior aspect of the
      superficial lobe. Lymph node biopsy yielded a diagnosis of small cell malignant
      lymphoma. The patient was referred to the medical oncology department for
      staging, further investigation, and planning of the treatment.

PMID- 16905912
TI  - [An alternative method for the correction of enophthalmos: deep lateral orbital
      approach].
AB  - Both increased orbital volume due to inadequate orbital floor reconstruction and
      loss of orbital volume may result in enophthalmos. Enophthalmos, vertical
      dystopia, and "lateral scleral show" deformity were detected in a 33-year-old
      female patient who presented with periorbital deformities after three operations
      for the correction of traumatic zygomatic fracture. First, vertical dystopia was
      repaired by reinforcing the orbital base with cranial bone grafting. Since
      enophthalmos was not successfully corrected, orbital volume augmentation was
      performed using the deep lateral wall through an upper eyelid crease incision.
      The only postoperative complaint was edema which was controlled by application of
      ice.

PMID- 16905913
TI  - Power failure: physicians are resorting to scare tactics.

PMID- 16905914
TI  - Wanted: nurses who support caregivers: why do family caregivers feel so abandoned
      by nurses?

PMID- 16905916
TI  - Supporting birth.

PMID- 16905926
TI  - Protecting patients or turf? The AMA aims to limit nonphysician health care
      professionals.

PMID- 16905927
TI  - Diabetes groups gather in DC in June: and the news is still bad.

PMID- 16905929
TI  - A case of airway obstruction: a rubber ball in a baby's throat didn't get there
      on its own. Is it abuse?

PMID- 16905930
TI  - Flooding: calming the storm within.

PMID- 16905931
TI  - FAMILY CAREGIVERS: caring for older adults, working with their families.
AB  - As the U.S. population ages and health care costs soar, family and friends are
      called upon increasingly to provide care. While the typical caregiver is a 46
      year-old woman with at least some college education, anyone in the infirm
      person's circle may be called upon to provide care. The kind of care provided
      varies greatly--from managing treatment and medication regimens to driving in
      from out of town to help with shopping--as does each caregiver's reaction to
      providing such care. While some find caregiving terribly stressful, others find
      it rewarding. Nurses need to know how to identify the primary caregiver, discern
      the level of strain caused by caregiving, and create a partnership with the
      caregiver to help ease the burden. Accompanying text explores one caregiver's
      experience.

PMID- 16905933
TI  - HIPAA and talking with family caregivers: what does the law really say?
AB  - The Health Insurance Portability and Accountability Act of 1996 (PL 104-191),
      known as HIPAA, has confused and unnecessarily alarmed many conscientious health
      care providers. Nurses in particular are likely to be on the front line of family
      caregivers' inquiries, because physicians are often difficult to reach and
      because family caregivers look to nurses as sources of reliable information. A
      major retraining of health care providers at all levels is needed to dampen the
      "HIPAA scare" and clarify what HIPAA does and does not say about communication
      with family caregivers.

PMID- 16905934
TI  - Nurses in a burn unit: photographs.

PMID- 16905935
TI  - Helping children with nocturnal enuresis: the wait-and-see approach may not be in
      anyone's best interest.
AB  - Nocturnal enuresis-defined as the involuntary passage of urine at night-is a
      common childhood condition. Although most will outgrow it, a wait-and-see
      approach is not appropriate if bedwetting is affecting the child's self-esteem or
      causing stress within the family. This article offers an overview of the causes
      and effects of the condition; discusses treatment options, including alarm
      therapy and medication; and describes ways that nurses can provide education and
      support.

PMID- 16905937
TI  - To nurse or not to nurse.

PMID- 16905938
TI  - C-reactive protein and cardiovascular disease in people with diabetes: high
      sensitivity CRP testing can help assess risk for future cardiovascular disease
      events in this population.
AB  - Having both diabetes and an elevated C-reactive protein (CRP) level compounds
      one's risk of developing cardiovascular disease, for which people with diabetes
      are at particularly high risk. CRP is both a biomarker for infectious and
      noninfectious disorders associated with inflammation and a risk factor for such
      conditions. Many researchers now believe that the protein also plays a role in
      the disease processes. The American Heart Association and the Centers for Disease
      Control and Prevention recently defined three cardiovascular risk categories
      relative to CRP levels. This article reviews the relevant literature and explores
      how CRP levels can be used in cardiovascular disease risk assessment, prevention,
      and treatment.

PMID- 16905941
TI  - Hazardous conditions: the ANA, nurses work to inform colleagues about safer drug
      handling.

PMID- 16905942
TI  - Where is the funding? Several proposed bills merit your voice and attention.

PMID- 16905943
TI  - The nurses of AARP: for the first time, three nurses lead AARP--as president
      elect, board chairperson, and board member.

PMID- 16905944
TI  - Night shifts and fatigue: coping skills for the working nurse.

PMID- 16905945
TI  - Degradation of extracellular matrix proteins (fibronectin, vitronectin and
      laminin) by serine-proteinases isolated from Lonomia achelous caterpillar
      hemolymph.
AB  - Lonomia achelous is a caterpillar distributed in southern Venezuela and in
      northern Brazil that causes an acute hemorrhagic syndrome in people who have
      contact with its bristles. The effect of the crude hemolymph and its
      chromatographic fractions (FDII, Lonomin V and Lonomin V-2) on extracellular
      matrix proteins was studied. The chromatographic fractions show activities
      similar to plasmin and urokinase. In sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis, both lonomins appear as a protein band of 25 kDa under reduced
      conditions. By exclusion chromatography, the molecular weights of Lonomin V and
      Lonomin V-2 were 26.5 and 24.5 kDa, respectively. Fibronectin, laminin and
      vitronectin were degraded by all venom components. Sodium dodecyl sulfate
      polyacrylamide gel electrophoresis, under reduced conditions, shows that lonomins
      degrade fibronectin in four main fragments of 116, 60, 50 and 30 kDa. Molecular
      exclusion chromatography in native conditions shows that the molecular masses of
      these fragments are > or = 300, 62 and 27 kDa. The proteolytic effect of lonomins
      was abolished by benzamidine/HCl, iodoacetic acid and aprotinin. The
      extracellular matrix protein degradation together with the fibrino(geno)lytic
      activity of hemolymph and its fractions could explain, in part, the hemorrhagic
      syndrome, and the wound dehiscence in persons who have had contact with the L.
      achelous caterpillar.

PMID- 16905946
TI  - Oral L-arginine administration does not inhibit thrombosis on an experimental
      model of arterial thrombosis: the effect on the apyrasic activity of the arterial
      wall.
AB  - Despite the extensive research on the pharmacology of L-arginine, there are only
      few data on its antithrombotic properties. We studied the effect of oral L
      arginine administration in a model of arterial thrombosis in rabbits divided into
      three groups: group 1, group without intervention; group 2, control group,
      treated with normal diet and submitted to the thrombosis-triggering protocol;
      group 3, treated for 2 weeks with L-arginine (2.25%) prior the protocol. L
      Arginine did not alter platelet aggregation nor coagulation parameters but
      reduced vascular activities of both ADPase (49.1 +/- 8.5 versus 28.9 +/- 8.3
      versus 18.8 +/- 10.3 nmoles inorganic phosphate/min per mg protein; mean +/- SD;
      group 1 versus group 2 versus group 3, respectively; ANOVA F = 19.21; P < 0.0001)
      and ATPase (97.8 +/- 15.8 versus 52.1 +/- 11.6 versus 31.9 +/- 16.3 nmoles
      inorganic phosphate/min per mg protein; mean +/- SD; group 1 versus group 2
      versus group 3, respectively; ANOVA, F = 34.65; P < 0.0001). L-Arginine did not
      reduce the thrombi area (17.1 mm, 9.02 and 48.07, versus 27.04 mm, 25.4 and
      70.39, median, percentile 25 and 75 respectively, P = 0.079; group 2 versus group
      3, respectively). In conclusion, oral L-arginine administration did not inhibit
      thrombosis, and, conversely, it significantly reduced the arterial wall ADPase
      and ATPase activities. This effect may limit its antithrombotic properties.

PMID- 16905947
TI  - International Society on Thrombosis and Haemostasis score for overt disseminated
      intravascular coagulation predicts organ dysfunction and fatality in sepsis
      patients.
AB  - We evaluated the score for disseminated intravascular coagulation (DIC) recently
      published by the International Society for Thrombosis and Haemostasis (ISTH) in a
      well-defined series of sepsis patients. Thirty-two patients suffering from severe
      sepsis and eight patients with septic shock were evaluated following the ISTH DIC
      score. Fibrin monomer and D-dimer were chosen as fibrin-related markers (FRM),
      respectively. DIC scores for nonsurvivors (n = 13) as well as for septic shock
      patients were higher (P < 0.04) compared with survivors and patients with severe
      sepsis, respectively. Using fibrin monomer and D-dimer, 30 and 25% of patients
      suffered from overt DIC. Overt DIC was associated with significantly elevated
      thrombin-antithrombin complexes and plasminogen activator inhibitor type-1 levels
      as well as with significantly lower factor VII clotting activity. Patients with
      overt DIC had a significantly higher risk of death and of developing septic
      shock. Since more than 95% of the sepsis patients had elevated FRM, the DIC score
      was strongly dependent on prolongation of the prothrombin time and platelet
      counts. The ISTH DIC score is useful to identify patients with coagulation
      activation, predicting fatality and disease severity. It mainly depends on the
      prolongation of the prothrombin time and platelet counts.

PMID- 16905948
TI  - Effect of phosphatidylcholine, phosphatidylethanolamine and
      lysophosphatidylcholine on the protein C/protein S anticoagulation system.
AB  - Phosphatidylserine is known to significantly accelerate the blood coagulation
      reaction. In a previous communication submitted for publication, we demonstrated
      that phosphatidylcholine, phosphatidylethanolamine and lysophosphatidylcholine
      showed effects on the blood coagulation reaction using the factor Xa-prothrombin
      reaction system, and discuss a new function of membrane phospholipids. The
      present study examined the role of phospholipids in the blood coagulation
      regulatory reaction (anticoagulation system), by studying the effects of
      phospholipids on the protein C/protein S reaction. We have established
      quantitative methods for measuring activated protein C activity and protein S
      activity, and used them to measure their activity after the addition of liposomes
      with different phospholipid compositions. We found that phosphatidylcholine
      inhibited activated protein C and protein S activities in a dose-dependent
      manner, as in the factor Xa-prothrombin reaction system. On the other hand,
      phosphatidylethanolamine and lysophosphatidylcholine showed no effect on
      activated protein C activity. Phosphatidylethanolamine inhibited and
      lysophosphatidylcholine accelerated coagulation activity in the factor Xa
      prothrombin system, but such effects were not observed in the protein C/protein S
      reaction system. The coagulation and anticoagulation reactions are exquisitely
      balanced by thrombin, with a role both as a procoagulant and anticoagulant.
      Therefore, it is understandable that phosphatidylethanolamine and
      lysophosphatidylcholine show different effects in the factor Xa-prothrombin and
      protein C/protein S reaction systems. It appears that coagulation and
      anticoagulation reactions are co-ordinated and controlled by changes in
      phospholipid composition of the cellular membrane where the coagulation reaction
      takes place.

PMID- 16905949
TI  - Successful management of pregnancy in women with a history of thrombotic
      thrombocytopaenic purpura.
AB  - Pregnancy is an initiating event for acute thrombotic thrombocytopaenic purpura
      (TTP). There is a high risk of relapse during pregnancy and of foetal morbidity.
      We describe five cases with successful maternal and foetal outcomes in patients
      with a history of TTP. Cases 1 and 2 presented with TTP in their first pregnancy
      and had second-trimester foetal losses. Case 3 had four TTP relapses and soon
      after achievement of clinical remission became pregnant. Case 4 presented with
      TTP and left-sided stroke in pregnancy. ADAMTS-13 activity was less than 5% at
      presentation in four patients and prior to therapy during pregnancy in cases 1-4.
      Case 5, who had a single acute episode of TTP and became pregnant 6 years later,
      had normal ADAMTS-13 activity throughout pregnancy. Only case 3 had evidence of
      an inhibitor on mixing studies. All five patients underwent close haematological
      and obstetric monitoring and continued low-dose aspirin throughout pregnancy.
      Patients 1-4 had regular plasma exchange and received low molecular weight
      heparin during pregnancy. Patient 4 also received rituximab during the third
      trimester with no observed maternal or neonatal toxicity. Live healthy infants
      were delivered in all five cases in the third trimester. These findings suggest
      that successful pregnancy outcome is achievable in patients with a history of TTP
      and that patients with severely reduced ADAMTS-13 activity at the onset of
      pregnancy, necessitates regular plasma exchange during pregnancy.

PMID- 16905950
TI  - Effect of phosphatidylcholine, phosphatidylethanolamine and
      lysophosphatidylcholine on the activated factor X-prothrombin system.
AB  - Membrane phospholipids are essential in blood coagulation reactions. The
      importance of negatively changed phosphatidylserine has been shown. The roles of
      other phospholipids in the blood coagulation system, however, are not clear. This
      study examined the effects of phosphatidylcholine on the blood coagulation system
      using liposomes containing varying concentrations of phosphatidylcholine in the
      presence of phosphatidylserine at a constant concentration. In addition, with
      phosphatidylserine and phosphatidylcholine at constant concentrations, the
      effects of phosphatidylethanolamine and lysophosphatidylcholine on the blood
      coagulation system were examined. Using an in vitro reconstructed system of the
      activated factor X-prothrombin system, blood coagulation was measured by the rate
      of thrombin formation after the addition of liposome preparations. The results
      showed suppression of the system by phosphatidylcholine and
      phosphatidylethanolamine and acceleration by lysophosphatidylcholine. The results
      of the present study suggest that the cell membrane, the 'location' of blood
      coagulation, is one of the regulatory factors, and that changes in
      phosphatidylcholine content and phospholipid composition of the cell membrane
      regulate the coagulation reaction.

PMID- 16905951
TI  - A daily glass of red wine induces a prolonged reduction in plasma viscosity: a
      randomized controlled trial.
AB  - Moderate red wine consumption has been associated with decreased risk of coronary
      heart disease. Reduced plasma viscosity and fibrinogen levels have been launched
      as possible contributors to this risk reduction. The effect of moderate red wine
      consumption on plasma viscosity, however, has not been investigated in a
      prospective, randomized trial. We wanted to evaluate the effect of moderate red
      wine consumption on plasma viscosity, fibrinogen concentration and fibrinogen
      subfractions. Healthy, nonsmoking volunteers were assigned to consume one glass
      of red wine daily for 3 weeks in a prospective, randomized cross-over study. In
      the second 3-week period the volunteers abstained from alcohol use. The plasma
      viscosity, fibrinogen concentration and the distribution of the main fibrinogen
      subfractions were determined at inclusion, after wine drinking and after
      abstention. Plasma viscosity was reduced by 0.026 and 0.024 mPa.s in the two
      groups following wine intake (95% confidence interval, 0.009-0.043, P = 0.004;
      95% confidence interval, 0.0083-0.039, P = 0.003). The decrease in plasma
      viscosity was maintained following 3 weeks of abstention. The fibrinogen
      concentration was reduced by 0.17 g/l following wine drinking in the group
      starting with abstention (95% confidence interval, 0.04-0.29, P = 0.01). The
      distribution of the fibrinogen subfractions remained unaltered. We conclude that
      a daily glass of red wine for 3 weeks significantly reduces plasma viscosity.
      Fibrinogen concentrations are also significantly reduced, when preceded by an
      abstention period. The decreased viscosity levels are maintained after 3 weeks of
      abstention, suggesting a sustained viscosity lowering effect of red wine.

PMID- 16905952
TI  - Detection of acquired resistance to activated protein C associated with
      antiphospholipid antibodies using a novel clotting assay.
AB  - Antiphospholipid antibodies (aPA) frequently interfere with the protein C
      pathway. This manifests as acquired activated protein C (APC) resistance in the
      absence of factor V Leiden and has been proposed as a putative mechanism for the
      pathogenesis of the antiphospholipid syndrome (APS). We have developed a
      Russell's viper venom test, performed with and without activation of endogenous
      protein C, which is sensitive to aPA-associated APC resistance. Results were
      reported as the endogenous APC ratio (EAPCr); the ratio of the two clotting times
      normalized against pooled normal plasma. Forty-four patients with aPA,
      anticardiolipin and/or lupus anticoagulant, including 34 with a history of
      thrombosis or pregnancy morbidity; a control group of aPA-negative patients; and
      26 healthy normals were studied. EAPCr (mean, SD) was significantly higher in APS
      patients (1.94, 0.58) than normals (0.98, 0.12) or controls (1.14, 0.19; P <
      0.00001). Elevated EAPCr (> 1.22) occurred in 91% of aPA-positive patients,
      predominantly due to resistance to APC (87%) rather than prolonged basal clotting
      times alone (15%). Significant correlation was observed between the EAPCr value
      and dilute Russell's viper venom time (rs = 0.44, P = 0.003), IgG anticardiolipin
      (rs = 0.54, P = 0.002), protein S (r = -0.46, P = 0.01) and activated partial
      thromboplastin time-based APC resistance (r = -0.61, P = 0.001). There was no
      significant relationship between EAPCr and protein C concentration, anti-beta2
      glycoprotein-I (anti-beta2GPI) or IgM anticardiolipin. Purified aPA IgG caused a
      dose-dependent increase in APC resistance when added to normal plasma. We
      conclude that aPA-associated acquired APC resistance is a common feature of APS
      and may be independent of anti-beta2GPI.

PMID- 16905953
TI  - Role of five platelet membrane glycoprotein polymorphisms in branch retinal vein
      occlusion.
AB  - To determine whether polymorphisms of platelet surface glycoprotein associated
      with arterial thrombosis are risk factors for branch retinal vein occlusion. A
      case-control study in which 69 patients with branch retinal vein occlusion and
      147 controls who attended the eye clinic for nonvascular complications
      participated. DNA was extracted from whole blood and analyzed for genotyping of
      platelet glycoprotein polymorphisms by polymerase chain reactions and specific
      restricted enzymes. No relationship was found between the four platelet
      glycoprotein polymorphisms i.e. GPIa C807T, VNTR and Kozak of glycoprotein
      Ibalpha, the HPA-1 of glycoprotein IIIa and the occurrence of branch retinal vein
      occlusion. The HPA-2 polymorphism was found in 18 out 60 (30%) patients with
      branch retinal vein occlusion in comparison with 27 out 142 (19%) of controls,
      with an estimated odds ratio of 1.8 (95% confidence interval, 0.91-3.65). The
      four platelet glycoprotein polymorphisms are not risk factors for branch retinal
      vein occlusion and therefore it seems unnecessary to screen those patients for
      it. A larger study is required, however, to determine whether HPA-2 is a novel
      risk factor for branch retinal vein occlusion.

PMID- 16905954
TI  - Chronic stage left ventricular aneurysm and thrombus after myocardial infarction.
AB  - A 60-year-old man had acute myocardial infarction 13 years ago. After
      percutaneous coronary intervention, the follow-up left ventriculography (8 years
      ago) showed dyskinesia in the anterolateral and apical segments of the wall.
      Following this, there was no change in the clinical symptom. After 6 years the
      patient discontinued aspirin without seeking medical advice. In this year, a
      thrombus was found in the left ventricle, and thrombectomy was performed. Left
      ventricular aneurysm has always been a risk for thrombogenesis in any stage, and
      a periodic follow-up including an echocardiogram and anticoagulation therapy is
      necessary.

PMID- 16905955
TI  - Life-threatening hematoma associated with paracentesis: a case report.
AB  - Deep venous thrombosis prophylaxis is recommended in all high-risk hospitalized
      medical patients. We describe a unique complication of paracentesis in a patient
      receiving unfractionated heparin for deep venous thrombosis prophylaxis. Our
      patient developed a very large rectus sheath hematoma and hypotension gradually
      after paracentesis. Heparin should be used with caution for deep venous
      thrombosis prophylaxis in patients undergoing paracentesis.

PMID- 16905956
TI  - Heterozygous methylenetetrahydrofolate reductase 677C-T gene mutation with mild
      hyperhomocysteinemia associated with intrauterine iliofemoral artery thrombosis.
AB  - Neonatal thrombosis is a serious event that can cause mortality or severe
      morbidity. Newborn-related factors, including genetic prothrombotic risk factors,
      may affect the occurrence of neonatal thrombosis. In this report, a case of
      intrauterine iliofemoral arterial thrombosis associated with mild
      hyperhomocysteinemia caused by methylenetetrahydrofolate reductase 677C-T gene
      mutation is presented. We suggest that methylenetetrahydrofolate reductase gene
      mutation might be investigated in neonates and their families presenting with
      thromboembolic disease.

PMID- 16905957
TI  - A novel factor XI gene mutation associated with mild factor XI deficiency in a
      symptomatic patient.
AB  - Congenital factor XI deficiency is a rare condition, in which plasma factor XI
      levels correlate poorly with the severity of haemorrhage. The condition is
      typically characterized by post-traumatic bleeding. The factor XI gene is located
      on chromosome 4 and contains 15 exons. More than 80 mutations have so far been
      described. We describe a novel mutation in the factor XI gene associated with
      mild factor XI deficiency. The patient, who is of Irish descent, has a history of
      post-traumatic bleeding and was found to have a borderline factor XI deficiency.
      DNA sequence analysis of the factor XI gene revealed a novel T to A mutation at
      nucleotide 168 resulting in the substitution of the cysteine residue at codon 38
      with a stop codon (Cys38STOP). The mutation predicts the premature termination of
      translation of factor XI mRNA resulting in a truncated, and probably unstable,
      factor XI protein. The presence of the mutation is consistent with the patient's
      borderline factor XI deficiency.

PMID- 16905958
TI  - Founder mutation Arg485Pro led to recurrent compound heterozygous GGCX genotypes
      in two German patients with VKCFD type 1.
AB  - Congenital combined deficiency of the vitamin-K-dependent coagulation factors
      (VKCFD) represents a rare autosomal recessive inherited bleeding disorder caused
      by mutations in either the gamma-glutamyl carboxylase gene (VKCFD type 1) or the
      vitamin K epoxide reductase gene (VKCFD type 2). Four different mutations of the
      gamma-glutamyl carboxylase gene (GGCX) have so far been reported in three
      unrelated patients with VKCFD type 1. Here we report on a fourth patient who
      presented with two compound heterozygous missense mutations of the GGCX gene,
      His404Pro and Arg485Pro. The His404Pro mutation has not been described
      previously, while the Arg485Pro mutation has been reported in another compound
      heterozygous VKCFD type 1 patient from Germany. Most interestingly, haplotype
      analysis revealed that Arg485Pro is due to a founder mutation, suggesting that
      this mutation is present in the German population at some low frequency. The
      founder mutation explains that the only two compound heterozygous VKCFD type 1
      patients known today originated from Germany.

PMID- 16905959
TI  - Patients who take uneven doses of acenocoumarol exhibit significant fluctuating
      levels of anticoagulation.
AB  - Acenocoumarol is the most widely used oral anticoagulant in Spain. In clinical
      practice it is usual to cut 4 mg tablets into halves and quarters, so that the
      total weekly dose may be uniformly distributed. Nevertheless, many patients are
      told to take uneven doses (e.g. 1/2 tablet one day and 1/4 tablet the next day).
      The impact of these variations in dosage over the stability of anticoagulation is
      unknown. We carried out a prospective study comparing a group of 40 patients
      taking uneven doses of acenocoumarol and another group of 10 patients with
      uniform doses. All patients were within the therapeutic range at inclusion in the
      study. The International Normalized Ratio (INR) was determined over two
      consecutive days in every patient to assess possible fluctuations of
      anticoagulation. Patients receiving an uneven dosage showed a greater variability
      of the INR value over two consecutive days, as opposed to patients receiving
      uniform doses. Variation of the INR resulted in a dose change in 27.5% of cases
      with uneven dosage and in none of the uniform dose cases. Consistent association
      was found between every INR value and the dose administered to the patient 2 days
      before (P < 0.01). Patients who take uneven doses of acenocoumarol exhibit
      significant fluctuating levels of anticoagulation. This fact has to be considered
      before making any change in the acenocoumarol dose. The INR value obtained
      depends greatly on the dose administered 2 days before determination of the INR.

PMID- 16905960
TI  - Effects of tadalafil on myocardial blood flow in patients with coronary artery
      disease.
AB  - OBJECTIVE: Erectile dysfunction and coronary artery disease share similar risk
      factors. Although phosphodiesterase-5 inhibitors used to treat erectile
      dysfunction do not adversely affect hemodynamic parameters in patients with
      coronary artery disease, their effects on myocardial blood flow are unknown.
      METHODS: In a randomized, double-blind, crossover study we examined the effects
      of tadalafil, 20 mg, compared with placebo on myocardial blood flow in patients
      with stable coronary artery disease (n=7, 52-73 years old). After tadalafil or
      placebo, myocardial blood flow was measured with positron emission tomography
      (nine-segment model) at rest, during maximal coronary hyperemia with adenosine,
      and during increased myocardial work with dobutamine. Abnormal flow was defined
      as myocardial blood flow <75% of maximum perfusion during adenosine plus placebo
      (46 normal/17 abnormal segments dentified). RESULTS: Compared with placebo,
      tadalafil had no significant effect on global myocardial blood flow at rest,
      during adenosine infusion, or during dobutamine infusion. Similarly, in normal
      and abnormal segments, tadalafil versus placebo had no significant effect on
      resting myocardial blood flow or on adenosine-induced increases in myocardial
      blood flow. In normal segments, myocardial blood flow with dobutamine plus
      tadalafil was greater than that with dobutamine plus placebo (1.79+/-0.56 versus
      1.56+/-0.37 ml/g per min, P<0.01), and in abnormal segments, there was a trend
      for tadalafil compared with placebo to increase myocardial blood flow during
      dobutamine infusion (1.46+/-0.44 versus 1.36+/-0.36 ml/g per min, P=0.7).
      CONCLUSIONS: Tadalafil had no significant effect on global myocardial blood flow
      at rest, during adenosine infusion, or during dobutamine infusion. Compared with
      placebo, tadalafil significantly augmented myocardial blood flow during increased
      workload in normal regions, with a trend toward improving myocardial blood flow
      in poorly perfused regions.

PMID- 16905962
TI  - Alterations in serum neopterin correlate with thrombolysis in myocardial
      infarction risk scores in acute coronary syndromes.
AB  - OBJECTIVES: Using serum neopterin as a marker of macrophage activation, we sought
      to examine the relationship between serum neopterin levels, thrombolysis in
      myocardial infarction (TIMI) risk scores, and how different treatments of acute
      coronary syndromes affect change in neopterin. METHODS: We examined serum
      neopterin concentrations at presentation and 72 h after treatment in 70 patients
      with acute coronary syndromes (35 with medical therapy, 25 with uncoated coronary
      stents, and 10 received rapamycin-eluting stents) using a commercially available
      immunoassay. Serum neopterin levels were determined for 36 patients with stable
      coronary artery disease. TIMI risk scores were calculated when appropriate
      (n=58). RESULTS: Serum neopterin had a strong correlation with the TIMI risk
      score on admission (P<0.0001). The mean baseline neopterin levels in patients
      with acute coronary syndromes stratified with TIMI scores between 1 and 7 were
      the following: patients with TIMI 1 scores had a level of 3.3+/-0.4 nmol/l, TIMI
      2 patients 4.6+/-0.6 nmol/l, TIMI 3 patients 5.5+/-1.4 nmol/l, TIMI 4 patients
      7.5+/-2.4 nmol/l, TIMI 5 patients 10.8+/-3.3 nmol/l, TIMI 6 patients 17.5+/-4.0
      nmol/l, and TIMI 7 patients 23.0+/-7.1 nmol/l. Mean changes in serum neopterin
      were significantly higher for the uncoated stent group than for each of the other
      three groups (P<0.05). CONCLUSIONS: Serum neopterin concentrations have a high
      correlation with TIMI risk scores and may represent a marker useful in
      stratifying patients with acute coronary syndromes. Our results also suggest that
      the use of uncoated coronary stents results in macrophage activation not found
      with other treatment modalities.

PMID- 16905961
TI  - Low risk is associated with poorer quality of life than high risk following acute
      coronary syndrome.
AB  - BACKGROUND: Morbidity after acute coronary syndromes includes both physical and
      mental disorders affecting quality of life. The aim of this investigation was to
      study quality of life at a 3-month follow-up in patients with acute coronary
      syndrome, with the main objective of exploring whether unstable angina pectoris
      and myocardial infarction (MI) patients differ in this respect. METHODS: This
      investigation was part of a prospective risk stratification study of consecutive
      patients with acute coronary syndrome of whom 814 below the age of 75 years (278
      diagnosed with unstable angina pectoris and 536 with myocardial infarction)
      accepted an invitation to a follow-up visit 3 months after discharge. At follow
      up, the patients completed the Cardiac Health Profile, a disease-specific quality
      of life questionnaire, designed to evaluate perceived cognitive, emotional,
      social and physical function. RESULTS: Quality of life was mainly influenced by
      patient characteristics and previous history. The Cardiac Health Profile scores
      in unstable angina pectoris patients were significantly higher (i.e. poorer
      quality of life) than myocardial infarction patients at the 3-month visit (34,
      22, 50; median, 25th, 75th percentile and 30, 19, 44; median, 25th, 75th
      percentile, respectively, P=0.006). The adjusted odds ratio for a poorer quality
      of life in unstable angina pectoris patients in relation to myocardial infarction
      patients was 1.39 (95% confidence interval 1.03, 1.87; P=0.03). The highest
      Cardiac Health Profile scores were seen in the unstable angina pectoris patients
      without electrocardiogram signs of ongoing ischemia and/or elevated markers of
      myocardial necrosis. CONCLUSION: Patients with unstable angina pectoris,
      especially of the low-risk type, and therefore treated accordingly, are more
      likely to experience poorer quality of life following an acute hospitalization
      than patients with other types of acute coronary syndrome. Once myocardial
      infarction or high-risk unstable angina pectoris has been ruled out, these
      patients still require a careful and systematic follow-up.

PMID- 16905963
TI  - Impact of mechanical reperfusion on clinical outcome in elderly patients with
      right ventricular infarction.
AB  - BACKGROUND: Previous reports suggest that elderly patients with acute right
      ventricular infarction suffer in-hospital mortality of 50% and that hemodynamic
      compromise is irreversible. We hypothesized that mechanical reperfusion would
      improve such outcomes. METHODS: We retrospectively analyzed in-hospital morbidity
      and mortality in 54 patients >70 years of age with acute inferior myocardial
      infarction undergoing primary angioplasty. The presence of right ventricular
      infarction was determined by a two dimensional echocardiogram. RESULTS: Overall,
      18 (33%) patients had inferior myocardial infarction and right ventricular
      infarction, whereas 36 (67%) patients had inferior myocardial infarction alone.
      All patients with inferior myocardial infarction alone were successfully
      reperfused, whereas one patient with right ventricular infarction suffered
      reperfusion failure. Right ventricular infarction patients more commonly suffered
      hemodynamic and arrhythmic complications (hypotension in 33 vs. 2.8%, P<0.01;
      ventricular arrhythmias in 61 vs. 25%, P<0.01; and bradyarrhythmias in 78 vs.
      25%, P<0.01). Overall, 72% of right ventricular infarction patients survived,
      including many with hemodynamic compromise. In-hospital mortality, however, was
      greater in those with right ventricular infarction than in those without (28 vs.
      8.3%, P=0.19). CONCLUSION: Elderly patients with inferior myocardial infarction
      complicated by right ventricular infarction suffer greater morbidity and
      mortality than those without. With successful mechanical reperfusion, however,
      the majority survives, including those with hemodynamic compromise.

PMID- 16905964
TI  - Lower prevalence of circulating natural killer T cells in patients with angina: a
      potential novel marker for coronary artery disease.
AB  - OBJECTIVE: Atherosclerosis is an inflammatory disease. Natural killer T cells are
      a unique lymphocyte subset that can recognize lipid antigens presented by CD1d
      and secrete copious amounts of pro-atherogenic cytokines such as interferon
      gamma. We have previously shown that natural killer T cells accelerate
      atherosclerosis in mice and macrophages incubated with oxidized low-density
      lipoproteins induce natural killer T cells to produce interferon-gamma. Thus,
      whether the prevalence of natural killer T cells in peripheral blood is altered
      in patients with angina pectoris and its correlation with coronary risk factors
      was determined. METHOD: Cell profiling was performed using flow cytometry in
      patients with stable angina, unstable angina (Braunwald IIIB), and healthy
      controls. Natural killer T cells in peripheral blood were identified by the
      expression of natural killer T specific invariant T cell receptor alpha-chain
      (Valpha24) and T cell receptor beta-chain (Vbeta11). RESULTS: Prevalence of
      natural killer T (Valpha24-Vbeta11 double positive) cells was significantly
      decreased in patients with unstable angina and stable angina compared with that
      in controls. No significant differences were observed in the prevalence between
      unstable and stable angina. Reduction of natural killer T cells was independently
      associated with the presence of angina. CONCLUSIONS: Lower prevalence of
      circulating natural killer T cells is related to the presence of coronary artery
      disease. As T cell receptor down-regulation or apoptosis after natural killer T
      cell activation and subsequent interferon-gamma release may contribute to
      atherogenesis, natural killer T cells can become a novel therapeutic target for
      the prevention and treatment of atherosclerotic vascular diseases.

PMID- 16905965
TI  - Metabolic syndrome increases the risk of significant coronary artery involvement
      in patients with peripheral artery disease.
AB  - BACKGROUND: Peripheral artery disease is a common condition, mainly associated
      with clinical cardiovascular risk factors. Patients with peripheral artery
      disease suffer from coronary artery disease-related complications. On the other
      hand, metabolic syndrome, as a constellation of specific risk factors, represents
      a risk factor for cardiovascular mortality. Metabolic syndrome might increase the
      risk of significant coronary artery disease in patients with peripheral artery
      disease. We aimed to examine the association of metabolic syndrome with the
      angiographically shown coronary artery involvement in patients with peripheral
      artery disease. METHODS: Two hundred and forty-seven patients with peripheral
      artery disease (mean age 60+/-9.5 years, 223 men/24 women), who were referred to
      coronary angiography, were evaluated. The resting ankle-brachial pressure index
      was measured with the patient in supine position. Patients with >70% diameter
      stenosis were considered to have significant coronary artery disease. RESULTS: In
      all, there were 223 male/24 female patients with mean ankle-brachial pressure
      index of 0.7+/-0.2, and mean age of 60+/-9.5 years. Metabolic syndrome was
      present in 53% (n=131) of all patients. Significant coronary artery disease was
      more frequently encountered in patients with peripheral artery disease and
      metabolic syndrome than in those without metabolic syndrome (73.3 vs. 40.5%,
      P<0.001). The presence of metabolic syndrome increased the risk of having
      significant coronary artery disease in patients with peripheral artery disease by
      4.027 fold. Lower ankle-brachial pressure index (P=0.038, B=2.567), older age
      (P<0.001, B=1.075), presence of metabolic syndrome (P=0.015, B=2.247), and
      presence of diabetes mellitus (P<0.001, B=1.293) were found to be independent
      predictors of significant coronary artery disease in patients with peripheral
      artery disease in multivariable regression. CONCLUSION: Metabolic syndrome seems
      to increase the risk of significant coronary artery disease in patients with
      peripheral artery disease.

PMID- 16905967
TI  - In-vivo accuracy of geometrically correct three-dimensional reconstruction of
      human coronary arteries: is it influenced by certain parameters?
AB  - OBJECTIVE: The geometrically correct three-dimensional reconstruction of human
      coronary arteries by integrating intravascular ultrasound (IVUS) and biplane
      angiography constitutes a promising imaging method for coronaries with broad
      clinical potential. The determinants of the accuracy of the method, however, have
      not been investigated before. METHODS: In total, 17 arterial segments (right
      coronary artery, n=7; left anterior descending, n=4; left circumflex, n=6)
      derived from nine patients were three-dimensionally reconstructed by applying
      three-dimensional intravascular ultrasound. The degree of matching between the
      reconstructed lumen back-projected onto each angiographic plane and the actual
      lumen in each plane was used as a measure of method's accuracy. The investigated
      factors that could potentially affect the reliability of the method included the
      type of the artery (left anterior descending, left circumflex, right coronary
      artery) and several geometrical and morphological characteristics of the
      reconstructed arteries. RESULTS: The correlation between the back-projected
      reconstructed lumens and the actual angiographic ones was found to be high
      (r=0.78, P<0.001). Neither the category of the reconstructed arteries nor their
      particular geometrical and morphological characteristics influenced the accuracy
      of the reconstruction method significantly. Nonetheless, the method exhibited
      slightly less accuracy in the reconstruction of right coronary arteries, an
      observation that could be attributed to the more intense pulsatile motion that
      this artery experiences during the cardiac cycle compared to the left anterior
      descending and left circumflex artery. CONCLUSIONS: The in-vivo accuracy of three
      dimensional intravascular ultrasound (3D IVUS) is significantly high regardless
      of the type of the coronary arteries or their particular geometrical and
      morphological characteristics. This finding further supports the applicability of
      the method for either diagnostic or investigational purposes.

PMID- 16905966
TI  - In-vivo validation of spatially correct three-dimensional reconstruction of human
      coronary arteries by integrating intravascular ultrasound and biplane
      angiography.
AB  - OBJECTIVES: The in-vivo validation of geometrically correct three-dimensional
      reconstruction of human coronary arteries by integrating intravascular ultrasound
      and biplane coronary angiography has not been adequately investigated. The
      purpose of this study was to describe the reconstruction method and investigate
      its in-vivo feasibility and accuracy. METHODS: In 17 coronary arteries (mean
      length, 85.7+/-17.1 mm) from nine patients, an intravascular ultrasound procedure
      along with a biplane coronary angiography was performed. From each angiographic
      projection, a single end-diastolic frame was selected in order to reconstruct the
      intravascular ultrasound catheter trajectory in space. In each end-diastolic
      intravascular ultrasound image, the lumen and media-adventitia contours were
      detected semi-automatically by an active contour algorithm. Each pair of contours
      was located on the catheter trajectory appropriately and interpolated with the
      adjacent pairs creating a three-dimensional volume of the arterial lumen and
      wall. The reconstructed lumen was back-projected onto both angiographic planes
      and the agreement between the back-projected and the angiographic luminal
      outlines was calculated. RESULTS: The angiogram-derived catheter length showed
      very high correlation (y=0.97 x + 1.8, P<0.001) and agreement with the
      corresponding pullback-derived values. Accordingly, the semi-automated
      segmentation of intravascular ultrasound images was also in significant
      correlation (r> or =0.96, P<0.001) and agreement with the reference manual
      tracing. The back-projected luminal borders showed good overall association with
      the corresponding angiographic ones (r=0.78, P<0.001) as well as remarkable
      agreement. CONCLUSIONS: Spatially correct three-dimensional reconstruction of
      human coronary arteries constitutes an imaging method with considerably high in
      vivo feasibility and accuracy.

PMID- 16905968
TI  - Contrast enhancement of coronary atherosclerotic plaque: a high-resolution,
      multidetector-row computed tomography study of pressure-perfused, human ex-vivo
      coronary arteries.
AB  - OBJECTIVES: The objective of this study was to investigate the effect of contrast
      injection on atherosclerotic coronary plaque attenuation measured using
      multidetector-row computed tomography. BACKGROUND: Recent multidetector-row
      computed tomography studies have described the characterization of coronary
      atherosclerotic plaque on the basis of Hounsfield unit values. The influence of
      contrast injection on the attenuation of individual plaque components, however,
      is unknown. METHODS: Using a pressurized perfusion system, 10 human coronary
      arteries were examined postmortem with multidetector-row computed tomography and
      histology. Pre-enhanced, peak-enhanced, and delayed enhanced multidetector-row
      computed tomography images were acquired during continuous perfusion of the
      vessel. A total of 37 focal atherosclerotic plaques were identified. Vessel wall
      attenuation was measured from multidetector-row computed tomography images during
      all three enhancement phases. On the basis of the histology, plaques were
      categorized as noncalcified (predominantly fibrous or predominantly fibrofatty),
      mixed calcified (calcified fibrous or calcified necrotic core), or densely
      calcified. The mean Hounsfield unit was compared among contrast phases for all
      plaques and in plaque subgroups. RESULTS: We observed contrast enhancement of
      atherosclerotic plaques within the vessel wall. For noncalcified plaques
      including both fibrous and fibrofatty plaques, the mean Hounsfield unit of the
      vessel wall during and after contrast injection exceeded the mean value before
      injection (t-test, P<0.002). CONCLUSION: The present study demonstrates that
      intra-arterial injection of iodinated contrast agent results not only in luminal
      enhancement but also in atherosclerotic plaque enhancement in pressure-perfused
      coronary arteries imaged ex vivo. Plaque enhancement should be considered when
      characterizing plaque components on the basis of Hounsfield unit with
      multidetector-row computed tomography.

PMID- 16905969
TI  - Association between the dosage and duration of statin treatment with coronary
      collateral development.
AB  - BACKGROUND: The coronary collateral circulation is an alternative source of blood
      supply to myocardium in the presence of advanced coronary artery disease and the
      therapeutic promotion of collateral growth appears to be a valuable treatment
      strategy in these patients. Although it has been shown in in-vivo studies that 3
      hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) promote
      vasculogenesis and accelerate coronary collateral development in ischemic
      tissues, there are discordant results in clinical studies. Our aim was to
      investigate the effect of statin therapy, including dosage and duration of
      treatment, on coronary collateral growth in patients with advanced coronary
      artery disease. METHODS: Study population consisted of 400 (306 men, with the
      mean age of 62+/-10 years) consecutive patients who have undergone clinically
      indicated coronary angiography and had at least one major coronary artery
      stenosis of > or =95%. Coronary collaterals were graded from 0 to 3 according to
      the Cohen-Rentrop method and patients with grade 0-1 collateral development were
      regarded as having poor collateral and patients with grade 2-3 collateral
      development were regarded as having good collateral. RESULTS: Among 400 patients,
      196 (48%) were on statin therapy. Patients with good collateral score were more
      likely to have stable angina pectoris as clinical presentation (P<0.001), and
      were on statin therapy (P=0.001), and have multivessel disease (P=0.003). Statin
      therapy for less than 3 months had no effect on collateral development (P=0.19);
      however, patients who were on statin therapy for more than 3 months had
      significantly better collateral development (P=0.002). Statin therapy had no
      effect on coronary collateral development in patients having <10 mg atorvastatin
      equivalent dose (P=0.13); however, patients having > or =10 mg atorvastatin
      equivalent dose had better collateral development (P<0.001). Diabetes mellitus
      was the only negative predictor for coronary collateral formation (P=0.03). On
      multivariate analysis, stable angina pectoris [odds ratio 2.88, 95% confidence
      interval (1.8-4.7), P<0.001], statin therapy with > or =10 mg atorvastatin
      equivalent dose [odds ratio 2.06, 95% confidence interval (1.3-2.6), P<0.001] and
      having multivessel disease [odds ratio 1.86, 95% confidence interval (1.16-3),
      P=0.01] were found to be associated with rich collateralization. CONCLUSION:
      Statin therapy (> or =10 mg atorvastatin-equivalent dose), stable angina pectoris
      and having multivessel disease are associated with enhanced coronary collateral
      development in patients with advanced coronary artery disease.

PMID- 16905970
TI  - Modalities to assess myocardial viability in the modern cardiology era.
AB  - Detection of viable myocardium in patients with left ventricular dysfunction has
      become an increasingly important guide to prognosis and treatment. This article
      reviews the current status and future potential for the application of modalities
      to assess myocardial viability. Imaging and other techniques that are reviewed
      are myocardial perfusion imaging by single-photon-emission computed tomography,
      positron-emission tomography, echocardiography, cardiac magnetic resonance
      technology, computed tomography and catheter-based endocardial mapping.

PMID- 16905971
TI  - Bibliography. Current world literature.

PMID- 16905973
TI  - Dilemmas in management of the small renal mass.

PMID- 16905974
TI  - Staging refinements in renal cell carcinoma.
AB  - PURPOSE OF REVIEW: Accurate pathologic staging systems provide valuable
      prognostic information. As our understanding of the biology of renal cell
      carcinoma improves, so does the staging system has undergo periodic modification.
      The modification of the tumor-node-metastasis staging system in 2002 has been
      applied to various populations, and several changes have been proposed. RECENT
      FINDINGS: The tumor diameter chosen as a break point in the staging system for
      noninvasive tumors is debated. Although 4 cm, the break point between T1a and T1b
      tumors, was chosen, in part, to select tumors amenable to partial nephrectomy,
      newer data show that this may no longer be appropriate. Size appears to have
      continual prognostic significance, especially in the range of 4-6 cm. T3a tumors
      with adrenal involvement appear to have a poor prognosis similar to T4 tumors. In
      addition, while renal sinus invasion may have a worse prognosis, perinephric fat
      invasion appears to have less impact on survival than overall tumor size.
      SUMMARY: Refinements of the current staging system on the basis of current
      understanding of tumor characteristics will improve prognostic accuracy. The
      addition of molecular markers and other features should be considered while not
      allowing increased complexity to disrupt clinical utility.

PMID- 16905975
TI  - Energy ablative techniques for treatment of small renal tumors.
AB  - PURPOSE OF REVIEW: The success of partial nephrectomy for the treatment of small
      renal cancers has led to the development of energy ablative technologies, which
      are less invasive alternatives for performing nephron-sparing surgery. Currently,
      cryoablation and radiofrequency ablation are the two most reported technologies.
      Both technologies use very different means to cause cellular injury.
      Additionally, three newer technologies, high-frequency ultrasound ablation, laser
      interstitial therapy, and microwave therapy are emerging in the literature.
      RECENT FINDINGS: Three- and 4-year data for cryoablation and radiofrequency
      ablation are now becoming available. On the basis of these studies, it is clear
      that ablative technologies can be effective treatments for select small renal
      tumors. It is also evident that both percutaneous and laparoscopic approaches
      offer minimal morbidity. SUMMARY: As long-term (5 years and greater) outcome data
      for ablative technologies accumulate, we are likely to see an increase in
      clinical reports, including more patients who may be candidates for extirpative
      surgery. Technology will advance, leading to smaller probes with larger treatment
      zones, making it possible to treat larger tumors and potentially even tumors in
      the advanced disease state.

PMID- 16905976
TI  - Hemostatic techniques during laparoscopic partial nephrectomy.
AB  - PURPOSE OF REVIEW: To review the current techniques and technologies being used
      for hemostatic control during laparoscopic partial nephrectomy. RECENT FINDINGS:
      Laparoscopic nephron-sparing surgery has become more common for the treatment of
      renal masses. With increasing experience, the indications for nephron sparing are
      increasing. Despite the increased use of these techniques in high-volume centers,
      however, more widespread application has been limited because of the need for
      advanced laparoscopic skills including the laparoscopic control of intraoperative
      renal bleeding. As a result, many techniques have been developed to achieve
      hemostasis, including conventional suture repair, tissue sealants, radiofrequency
      ablation, lasers, water dissection, and microwave tissue coagulation. SUMMARY:
      Laparoscopic partial nephrectomy is a technically challenging procedure. Many
      promising techniques are being developed currently, most geared toward improved
      hemostasis and collecting system repair. These techniques and products have made,
      and will continue to make, the procedure less demanding and more universally
      accepted.

PMID- 16905977
TI  - Current status and future directions of molecular markers in renal cell
      carcinoma.
AB  - PURPOSE OF REVIEW: To describe the existing data regarding the prognostic and/or
      predictive value of molecular markers in metastatic renal cell carcinoma. RECENT
      FINDINGS: Several molecular markers have been investigated in metastatic renal
      cell carcinoma for prognostic and/or predictive potential, many of which relate
      to pathogenic molecular alterations that are now therapeutic targets. Carbonic
      anhydrase IX is a von Hippel-Lindau (VHL)-mediated enzyme expressed in the
      majority of renal cell carcinoma tumors. High (>85%) expression of carbonic
      anhydrase IX in renal cell carcinoma tumors is a favorable prognostic marker and
      may predict response to interleukin-2 therapy. B7-H1 is a glycoprotein with
      inhibitory effects on T cells. B7-H1 expression in renal cell carcinoma tumor
      cells and/or lymphocytes may confer a worse survival in renal cell carcinoma
      patients, perhaps through impairment of inherent host of antitumor immunity. VHL
      pathway elements, including VHL gene status and expression of vascular
      endothelial growth factor protein and receptor, represent a promising area of
      investigation to predict responses to vascular endothelial growth factor-targeted
      agents. Prognostication schemas are beginning to incorporate molecular markers
      with clinical variables to refine the prediction of patient outcome. SUMMARY:
      Several molecular markers appear promising to refine prognosis and prediction in
      metastatic renal cell carcinoma. Further prospective evaluation is needed.

PMID- 16905979
TI  - Urinary bladder cancer: hard times for evidenced-based data.

PMID- 16905978
TI  - New treatment approaches in metastatic renal cell carcinoma.
AB  - PURPOSE OF REVIEW: Recent developments in the understanding of the molecular
      biology of renal cell carcinoma have led to the development of several biologic
      agents with different mechanisms of action. In 2005, promising results have been
      observed especially in second-line therapy following cytokine failures and in
      2006 more mature data with regard to time to progression and overall survival
      should be available. This review, analyzing basic translational research
      principles, will summarize the available evidence with a glimpse of the future
      therapeutic approaches in renal cell carcinoma. RECENT FINDINGS: Vascular
      endothelial growth factor- and platelet-derived growth factor receptor-inhibiting
      drugs (SU11248, Bay 43-9006, Bevacizumab, AG-013736, etc.) report time to
      progression ranging between 4 and 9 months and variable benefits in overall
      survival. Confirmatory studies are ongoing regarding other novel treatments (CCI
      779, Infliximab, PTK-787). SUMMARY: In renal cell carcinoma, there is a strong
      rationale for targeting multiple pathways and particularly angiogenesis. Vascular
      endothelial growth factor- and platelet-derived growth factor receptor-inhibiting
      drugs have been rapidly approved in the second-line setting and will soon be used
      as first-line therapy. In the next years, translational/clinical research will
      provide evidence for combination strategies to improve upon the results of the
      biologic agents and hopefully offer more hope to patients with renal cell
      carcinoma.

PMID- 16905981
TI  - Urinary markers in the detection of bladder cancer: what's new?
AB  - PURPOSE OF REVIEW: Bladder cancer is one of the most common genitourinary
      malignancies and is a potentially life-threatening diagnosis. For many patients,
      however, the diagnosis of bladder cancer entails a lifetime of vigilant, costly,
      and invasive surveillance for recurrent and/or progressive disease. In the
      context of relative limitations of the current standard of cystoscopy and
      cytology, there has been burgeoning activity in the development of novel
      molecular urine-based markers for bladder cancer detection. RECENT FINDINGS: A
      large number of candidate bladder cancer biomarkers have emerged as our
      understanding of the molecular pathogenesis of the disease has evolved. Many of
      these are in the relatively earlier phases of development but several have
      received the approval of the United States Food and Drug Administration for
      clinical use and are already being applied to patients in clinical practice.
      SUMMARY: Urine-based markers for bladder cancer detection represent an area of
      substantial innovation and discovery with potentially profound scientific,
      clinical, and economic implications. As more of these tests become standardized
      and undergo evaluation in large multicenter trials, it is conceivable that a
      novel marker or panel of markers will emerge as a major enhancement to the
      current standard of care.

PMID- 16905980
TI  - Should cystectomy only be performed at high-volume hospitals by high-volume
      surgeons?
AB  - PURPOSE OF REVIEW: Monitoring and improving the quality of healthcare is an
      evolving process that involves patients, physicians, and healthcare purchasers.
      Growing interest is seen in addressing quality concerns with policy changes.
      Surgeon and hospital volumes for specific high-risk procedures have been shown to
      be predictive of posttreatment outcome, but debate continues as to if the
      evidence justifies changes in practices. We reviewed the literature for robust
      evidence that surgeon and hospital volumes are markers of improved outcome of
      radical cystectomy. RECENT FINDINGS: Outcome can be measured by postoperative
      mortality, as well as complication rate, recurrence rate, and several other
      factors. Evidence suggests that outcome is improved after cystectomy performed at
      high-volume centers and by high-volume surgeons. The limitations of volume-based
      referral policies are discussed, and the use of alternative strategies is
      reviewed. SUMMARY: A significant regionalization of cystectomy has already been
      established. Owing to their limitations, however, volume-based referral systems
      have not been embraced by all parties. New strategies will continue to evolve,
      and validation of these strategies will be required before clinical
      implementation.

PMID- 16905982
TI  - Quality of life after therapy for muscle-invasive bladder cancer.
AB  - PURPOSE OF REVIEW: Therapy for invasive bladder cancer should aim at cure, and
      besides radical organ-removing surgery, bladder-sparing alternatives are
      available. Here I report the current status on quality-of-life issues after
      therapy for invasive bladder cancer. RECENT FINDINGS: Consensus has not been
      reached on the definition of the concept 'quality of life', resulting in numerous
      ways of measuring it. It is reasonable to believe that the individually self
      assessed level of quality of life is affected by the total post-therapeutic
      symptom burden, that is, the long-term side effects of a therapy are predictors
      for quality of life. The affection on quality of life by a symptom on an
      individual can never be predicted because of differences in symptom tolerance. On
      the group level, however, some symptoms are generally highly distressful, whereas
      others are generally low distressors. A new area of quality-of-life research is
      evolving, measuring symptoms, symptom distress and effects on quality of life.
      SUMMARY: Cystectomy followed by orthotopic bladder replacement seems to keep a
      high level of quality of life in select cases; however, ileal conduit is still an
      excellent option in other patients. Bladder-sparing alternatives are available.
      An individual pre-therapeutic consultation will aid in determining the radical
      therapeutic method in each individual patient.

PMID- 16905983
TI  - Intravesical gemcitabine: an update of clinical results.
AB  - PURPOSE OF REVIEW: Nonmuscle-invasive bladder cancer is a common malignancy,
      standardly treated by transurethral resection and adjuvant intravesical
      instillations of chemotherapy or immunotherapy. Adjuvant instillations are needed
      to reduce recurrence and/or progression. With currently existing adjuvant
      treatments, however, recurrences still occur, progression is hardly influenced
      and these treatments induce local or systemic side effects. In search for
      efficacy improvement and side effect reduction, we reviewed the promising
      properties of the relatively new intravesical drug, gemcitabine. RECENT FINDINGS:
      The safety of gemcitabine is tested in different instillation schemes, drug
      concentrations and administered volumes. Its safety profile is excellent, with
      good tolerability and minimal toxicity up to 2000 mg/50 ml for 2-h instillations.
      In comparison with other drugs, the ablative efficacy of gemcitabine is good. The
      first studies on prophylactic efficacy in intermediate-risk, high-risk and
      bacillus Calmette-Guerin-refractory patients are promising but limited by the
      small number of patients studied. SUMMARY: The available literature underlines
      the promising properties of gemcitabine for the intravesical use against
      nonmuscle-invasive bladder cancer. Exploring phase-II and comparative randomized
      phase-III studies should provide additional information on gemcitabine and its
      benefit to clinical practice.

PMID- 16905984
TI  - Lymphovascular invasion as a prognostic tool for advanced bladder cancer.
AB  - PURPOSE OF REVIEW: Lymphovascular invasion has been correlated with the
      metastatic ability of the cancer. It has been studied in urological tumours at
      every location, but it has only been included as a prognostic factor in the TNM
      (tumour, lymph nodes and metastasis) classification of germ cell testicular
      tumours. The purpose of this evaluation is to look into the predictive value of
      lymphovascular invasion in locally advanced bladder cancer. RECENT FINDINGS:
      Studies carried out in patients who underwent cystectomy report a lymphovascular
      invasion incidence of 30-50% of the cases. All of them agree that there is a
      correlation between the presence of lymphovascular invasion and disease
      evolution, but some authors consider that only blood vessel invasion is a
      statistically significant independent prognostic factor, and others find that
      this happens only in lymph node-negative cases. SUMMARY: All papers stress the
      prognostic value of lymphovascular invasion, most of them as an independent
      factor, but there are still some doubts as to its use in clinical decision
      making, owing to the poor diagnosis reproducibility. This is why it would be
      necessary to reach a consensus on strict diagnostic criteria as soon as possible
      to be able to incorporate this prognostic factor in clinical practice.

PMID- 16905985
TI  - Fluorescence cystoscopy: is it ready for use in routine clinical practice?
AB  - PURPOSE OF REVIEW: To review the recent literature on the use of fluorescence
      cystoscopy in the diagnosis and management of bladder cancer. RECENT FINDINGS:
      Recent advances have been made in fluorescence cystoscopy with the use of newer
      fluorescence agents (hexylester aminolevulinate and hypericin) and their
      application to flexible cystoscopy. Within several hours of intravesical
      administration of these agents, bladder tumors can be detected using fluorescence
      cystoscopy resulting in improved cancer detection and lower short-term recurrence
      rates than white light cystoscopy. Preliminary results with flexible fluorescence
      cystoscopy suggest that this technique can be used for office-based cystoscopy.
      SUMMARY: Significant advances have been made in the field of fluorescence
      cystoscopy. The currently available fluorescence agents in recent phase II and
      III trials outperform white light cystoscopy in terms of cancer detection and
      recurrence-free survival. Fluorescence cystoscopy should be considered as an
      adjunctive tool for the diagnosis and management of superficial bladder cancer.

PMID- 16905986
TI  - Recent developments in molecular profiling of bladder cancer.
AB  - PURPOSE OF REVIEW: Profiling bladder tumors using high-density microarrays has
      recently become possible. We review recent reports on the use of profiling for
      the prediction of various clinical courses in bladder cancer. We also stress the
      methods and materials needed to translate such molecular profiles into clinically
      useful tests. RECENT FINDINGS: Using gene expression microarrays, it has been
      possible to identify signatures that predict various properties of bladder cancer
      such as stage, grade, progression, and likelihood of metastases. Using arrays for
      genomic instability, similar properties have been examined, but the effectiveness
      seems to be less than that of gene expression. Some of genes identified also work
      as predictors using immunohistochemistry. SUMMARY: The signatures or molecular
      profiles for some of these arrays are now being tested in multicenter studies
      with the purpose of introducing these into the clinic, for planning of follow-up
      and treatment selection.

PMID- 16905987
TI  - Bibliography. Current world literature. Bladder cancer.

PMID- 16905988
TI  - The developing manager.

PMID- 16905989
TI  - Impact of Medicare's prospective payment system on hospitals, skilled nursing
      facilities, and home health agencies: how the Balanced Budget Act of 1997 may
      have altered service patterns for Medicare providers.
AB  - The prospective payment system is one of many changes in reimbursement that has
      affected the delivery of health care. Originally developed for the payment of
      inpatient hospital services, it has become a major factor in how all health
      insurance is reimbursed. The policy implications extend beyond the Medicare
      program and affect the entire health care delivery system. Initially implemented
      in 1982 for payments to hospitals, prospective payment system was extended to
      payments for skilled nursing facility and home health agency services by the
      Balanced Budget Act of 1997. The intent of the Balanced Budget Act was to bring
      into balance the federal budget through reductions in spending. The decisions
      that providers have made to mitigate the impact are a function of ownership type,
      organizational mission, and current level of Medicare participation. This article
      summarizes the findings of several initial studies on the Balanced Budget Act's
      impact and discusses how changes in Medicare reimbursement policy have influenced
      the delivery of health care for the general public and for Medicare
      beneficiaries.

PMID- 16905990
TI  - The role of clinical information systems in health care quality improvement.
AB  - This article addresses the increasing use of electronic medical records and
      supporting clinical information systems in US hospitals. It also addresses the
      current barriers to implementation of digital technology, which include cost,
      cultural factors, and the reluctance to embrace new technology. However, despite
      the barriers, there is evidence from the Veteran's Administration, Partners'
      HealthCare, Kaiser Permanente, and other organizations that electronic medical
      records and clinical information systems are a worthwhile investment. The
      benefits of the electronic medical records include the reduction of errors,
      improvement in clinical decision making during patient encounters, and universal
      access to information in real time. From a managerial perspective, health care
      organizations should adopt such systems to improve quality of care and to stay
      competitive in the marketplace. From a policy perspective, the electronic medical
      record provides an opportunity for integration of patient information and
      improves efficiency and quality of care across a wide range of patient
      populations.

PMID- 16905991
TI  - Valuable human capital: the aging health care worker.
AB  - With the workforce growing older and the supply of younger workers diminishing,
      it is critical for health care managers to understand the factors necessary to
      capitalize on their vintage employees. Retaining this segment of the workforce
      has a multitude of benefits including the preservation of valuable intellectual
      capital, which is necessary to ensure that health care organizations maintain
      their competitive advantage in the consumer-driven market. Retaining the aging
      employee is possible if health care managers learn the motivators and training
      differences associated with this category of the workforce. These employees
      should be considered a valuable resource of human capital because without their
      extensive expertise, intense loyalty and work ethic, and superior customer
      service skills, health care organizations could suffer severe economic
      repercussions in the near future.

PMID- 16905992
TI  - Reorganizing care and work: process and productivity gains.
AB  - A Montreal-area hospital implemented organizational changes to improve the
      psychosocial environment for patients and health care workers and enhance
      organizational efficiency. This article describes a participatory approach to
      improving the organization of care and work, an approach focused on productivity
      gains in an organization. Productivity gains were analyzed in 13 units of the
      Department of Nursing, which had introduced a series of organizational changes.
      Changes introduced in care and work organization led to productivity gains in all
      units overseen by the Nursing Directorate. A reorganization of care and work
      based on the psychosocial work environment and staff participation can have
      positive outcomes, both for employees and for the wider organization.

PMID- 16905993
TI  - Managed care and the bottom line of your practice.
AB  - Managed care has greatly influenced the health care industry, particularly with
      regard to reimbursement for medical services. Managed care has had and continues
      to have a significant impact on reimbursement for physician services. When
      contractual relations with managed care companies are initiated and managed by
      medical practice administrators, the result can be beneficial to a physician
      practice's financial bottom line. This article discusses the necessity to develop
      effective working relationships with managed care companies and suggests
      strategies for establishing fee schedules and negotiating reimbursement
      contracts.

PMID- 16905995
TI  - The Nursing Extern Program: innovative strategies for students in transition.
AB  - Within the present context of a shortage of nursing personnel, it seems crucial
      for organizations to find strategies that facilitate the transition from the
      student to the nurse role in order to recruit and retain caring and competent
      professionals. Early exposure to clinical nursing practice can (1) promote an
      appreciation of the organization and functioning of the clinical unit, (2)
      facilitate the application of knowledge and acquisition of nursing interventions,
      and (3) engage motivated nursing students in the learning process. L'Ordre des
      Infirmieres et Infirmiers du Quebec initiated the Nursing Extern Program (the
      Program) to ease the severe nursing shortage, which was expected to worsen over
      the summer. The Program was seen as a way for students to consolidate the
      learning acquired during clinical rotations. Nursing students were employed as
      externs over the summer period. Within the confines of the Program, nursing
      students had the opportunity to practice 21 nursing care activities while under
      the direct supervision of an expert nurse. This article describes the L'Ordre des
      Infirmieres et Infirmiers du Quebec Program and identifies the key elements of a
      hospital-based program. In the first 2 years of implementation, the Program
      retained 62% of the externs as graduates.

PMID- 16905996
TI  - The magnet designation process: a qualitative approach using Donabedian's
      conceptual framework.
AB  - Twelve nurse leaders and 12 registered nurses from 2 hospitals were interviewed
      to gain an understanding on the process for preparing for magnet designation.
      These leaders and nurses provided insight into whether a cultural shift within
      the organization was occurring while striving for magnet designation and the
      level of staff nurses' engagement during the process. Donabedian's framework
      provided the conceptual context for this study. According to Donabedian, stable
      organizational structures will influence professional nursing processes and
      result in better outcomes as measured by magnet status. The authors discuss how a
      magnet culture is achieved when structural factors such as adequate staffing and
      pay are present before building the processes, as well as the ways certain
      ingredients such as professional governance councils need to be primed to achieve
      the desired magnet outcome. However, transforming the culture into a "valued
      practice" magnet organization entails a paradigm shift marked by the willingness
      to share information and the depth and breadth of commitment toward staff
      engagement in fulfilling the mission of a culture that truly values nursing
      expertise.

PMID- 16905997
TI  - National health system steps in Turkey: concerns of family physician residents in
      Turkey regarding the proposed national family physician system.
AB  - Many countries are currently struggling with the public desire for improved
      health care and provision of basic services on the one hand, and the rising costs
      of health care on the other. Turkey is acutely experiencing this problem because
      of its relatively advanced level of economic development and its relatively low
      level of health status compared to Organization for Economic Cooperation and
      Development and European Union countries. Since 1990, there has been vigorous
      debate in the Turkish society regarding the best way to improve public health
      through improved primary health care. The current government is pursuing a
      proposal that has been mentioned before, but in a more serious effort than has
      been previously made. This is an approach to primary care based on systems such
      as those in the United Kingdom and in Germany, and the basic components are
      family physicians who have a particular list of patients whom they provide care
      for. Financing of the system is to be provided with a new general health
      insurance scheme. In this study, 38 family practice residents at the 3 major
      training hospitals for this specialty completed an investigator-designed
      questionnaire for the purpose of characterizing their concerns regarding this
      proposed system of primary health care delivery. The participants' responses
      indicated that the new system, which is known as the Family Physician System,
      will contribute importantly toward raising the overall level of health in Turkey.
      Specific expected benefits include closer patient-physician relationships,
      increased job satisfaction on the part of family physicians, and an overall
      increase in income for the physicians working in the system.

PMID- 16905998
TI  - The Bachelor of Science in Nursing degree as entry level for practice:
      recapturing the vision in the United States.
AB  - The requirement for the baccalaureate degree for entry into nursing practice is
      spreading throughout many countries of the world. In the United States, a similar
      movement has lain dormant for 4 decades. Here, the nursing education settings of
      the United States and Australia are compared and contrasted, describing how the
      systems, which were once similar, went in different directions as the United
      States began to rely heavily on 2-year associate's degree programs. This article
      advances the importance of developing a vision for the future of nursing in the
      United States, in which the Bachelor of Science in Nursing degree is the entry
      level standard.

PMID- 16905999
TI  - Sustainability of cross-functional teams for marketing strategy development and
      implementation.
AB  - This article presents a case study on a cross-functional team used for marketing
      strategy development and execution at a health insurance company. The study found
      a set of success factors that contributed to the initial success of the team, but
      the factors were not enough to maintain the team's high level of productivity
      over time. The study later identified a set of 8 factors that helped sustain the
      team's high-productivity level. The 2 sets (ie, success and its subsequent
      sustainability factors) are analyzed against a normative model of team
      effectiveness. All the factors are explained by the normative model except for 1
      sustainability factor, "challenge motivator." In fact, the study found the
      "challenge motivator" to be the most critical factor to keep up the team's
      productivity over time. Apart from a performance crisis, the authors developed 3
      "challenge motivators"--first, more granular market information that could
      unearth hidden performance issues; second, constant value creation to
      shareholders as the firm being publicly traded; and third, the firm's strategic
      mandate to meet and exceed customer expectations that puts ultimate performance
      pressure on the marketing strategy team.

PMID- 16906000
TI  - Wasteful use of financial resources in public hospitals in Turkey: a trend
      analysis.
AB  - The Turkish health system is mainly financed by public sources such as taxes and
      premiums collected from workers. According to 2003 data, total health
      expenditures were 4.5% of the country's Gross Domestic Product. Currently, 56% of
      the system is financed by the Ministry of Health, and services are also provided
      by the Ministry. The main sources of finance among the Ministry of Health
      hospitals are general budget contributions made by the Ministry and revolving
      funds. The purpose of this study is to evaluate the financial conditions of those
      Ministry of Health hospitals that have revolving funds. The financial trends of
      2514 hospitals were followed from 1996 to 2000, and financial statement analyses
      were conducted. The results of the study show that the Ministry of Health
      hospitals are not professionally administered for their financial situation and
      also that their financial resources are not used effectively. The hospitals had
      difficulty in collecting debts and had problems in cash returns. At the end of
      the study, policy suggestions are made for health care managers toward improving
      financial conditions in these public hospitals.

PMID- 16906001
TI  - The Monte Carlo method improves physician practice valuation.
AB  - This article demonstrates the use of the Monte Carlo simulation method in
      physician practice valuation. The Monte Carlo method allows the valuator to
      incorporate probability ranges into the discounted cash flow model and obtain an
      output indicating the probability for specified ranges of practice valuation.
      Given the high level of uncertainty in projected cash flows associated with
      physician practices, the value of this kind of information in a practice
      valuation decision would quite obviously be superior to any single point estimate
      generated by a traditional discounted cash flow model. It is postulated that
      virtually all hospitals support an information system that can easily accommodate
      a Monte Carlo simulation.

PMID- 16906002
TI  - The relationship of otitis media in early childhood to attention dimensions
      during the early elementary school years.
AB  - This study examined the impact of otitis media with effusion (OME) and associated
      hearing loss between 6 and 48 months of age on attention dimensions (i.e.,
      selective/focus, sustained) during the elementary school years. A prospective
      cohort design in which 74 African American infants were recruited between ages 6
      and 12 months. Ear examinations were done repeatedly using both otoscopy and
      tympanometry, and hearing was assessed using standard audiometric procedures
      between 6 and 48 months. Multiple measures of attention (i.e., direct assessment,
      behavioral observations, parent/teacher ratings) were administered from
      kindergarten through second grade to assess two theoretical dimensions of
      attention: selective/focused and sustained. The home environment was assessed
      annually. Results indicated that neither early childhood OME nor hearing loss
      showed significant correlations with any of the longitudinal or cross-sectional
      measures of selective/focused attention and sustained attention. In contrast,
      children with mothers who had fewer years of education and who lived in less
      responsive and supportive home environments scored higher on both parent and
      teacher ratings of sustained attention (i.e., hyperactivity) through the second
      grade of elementary school. For NEPSY Auditory Attention in second grade, a
      significant interaction between the Home Observation for Measurement of the
      Environment and hearing loss was uncovered. This interaction showed that children
      with hearing loss from poor home environments experienced greater difficulties on
      the NEPSY Auditory Attention task than those with hearing loss from good home
      environments. These findings do not support a direct linkage of a history of OME
      and associated hearing loss to difficulties in selective/focused attention or
      sustained attention in early elementary school children. Relationships between
      sociodemographic variables and attention-related functions appear stronger and
      should be considered as mediators in any examination of the linkages between
      early OME and subsequent attention functions.

PMID- 16906003
TI  - Long-term outcomes of adaptive functions for children with mucopolysaccharidosis
      I (Hurler syndrome) treated with hematopoietic stem cell transplantation.
AB  - Advances in medical treatment have prolonged the lives of children with Hurler
      syndrome or mucopolysaccharidosis I requiring increased attention to the
      assessment of their long-term outcomes and functional abilities. Adaptive
      functions are critical for understanding functional outcomes after treatment and
      developing focused interventions. We investigated the development of various
      adaptive functions in children who have had hematopoietic stem cell transplant
      (HSCT) for Hurler syndrome and risk factors that are associated with the
      development of these functions. We examined the development of 41 children who
      had 3 or more Vineland Adaptive Behavior Scales records assessed before and after
      transplant. Communication, daily living skills, socialization, and motor
      functions were measured. While standard scores decline over time, development of
      skills continue with a slower than average rate compared with peers. A cross
      sectional nontransplanted comparison group showed more deficits after age 2 years
      than the transplanted group. In contrast to cognitive ability, age at transplant
      was not significantly associated with ultimate adaptive level. Baseline cognitive
      level before HSCT and growth of cognition after HSCT were associated with
      adaptive functions especially for communication and daily living skills.
      Socialization was predicted by cumulative medical risk factors, likely due to
      restricted social exposure in children with complicated transplant courses.
      Overall, measurement of adaptive behaviors demonstrated that HSCT allows long
      term slow improvement of functional outcomes for children with Hurler syndrome.
      Children with Hurler syndrome with good cognitive levels before HSCT and
      continued growth of cognition after HSCT show good adaptive functions. Although
      cognitive and orthopedic problems as well as medical complications limit adaptive
      ability, identifying these problems early allow beneficial targeted
      interventions.

PMID- 16906005
TI  - From risky behavior to health risk: continuity across two generations.
AB  - The purpose of this study was to determine the impact of childhood aggression and
      social withdrawal on adolescent health risk behaviors and adult health outcomes,
      and to examine the transfer of health risk to preschool offspring. This was a
      prospective, longitudinal, and intergenerational study of 114 mothers from
      disadvantaged neighborhoods, who were identified in childhood as being highly
      aggressive and/or withdrawn or with low scores on these 2 behavioral risk
      dimensions, and their preschool offspring aged 1 to 6 years old. The health
      histories of mothers (adolescent health risk behavior, health during pregnancy,
      current symptoms) and target children were taken during structured interviews
      conducted at home. Regression analyses tested the relationship between maternal
      childhood risk status and subsequent health outcomes, and these were followed by
      structural equation modeling of a proposed intergenerational pathway. Maternal
      childhood aggression predicted current health risk behaviors (e.g., daily
      cigarette smoking), whereas maternal childhood social withdrawal was not
      associated with maternal health risk at the time of testing. Mothers who had high
      scores on both aggression and withdrawal were more likely to engage in adolescent
      health risk behavior, which was directly related to health problems in
      preschoolers (even after controlling for covariates, such as neonatal health
      status and sex). In summary, there are distinct health trajectories for women who
      are highly aggressive and socially withdrawn in childhood, with implications for
      women's long-term health. Specifically, aggression in girls is likely to lead to
      health risk behaviors that may also place the next generation at risk for
      pediatric illness. Results are interpreted in terms of the health-hostility link,
      best known in adult men and intergenerational models.

PMID- 16906006
TI  - Accuracy of caregiver identification of developmental delays among young children
      involved with child welfare.
AB  - Underidentification of developmental delays among young children involved with
      child welfare/child protective services (CW) is problematic. Caregivers of young
      children involved with CW may help increase identification of young children with
      developmental delays, but the accuracy of caregiver identification in this
      population and whether this varies by caregiver type is not known. This study
      uses data from the National Survey of Child and Adolescent Well-Being to
      determine if (1) caregivers of young children involved with CW accurately
      identify children with developmental delays and (2) foster caregivers are better
      able to identify developmental delays compared with other caregivers. Close to
      half the children had a delay in language, cognitive, and/or adaptive behavior
      (45%). Overall sensitivity for caregiver identification was 35% (95% confidence
      interval [CI]: 29%, 41%); specificity was 84% (95% CI: 80%, 87%). After
      controlling for certain child and caregiver characteristics, in-home caregivers
      had 0.15 times the odds of identifying a child with a developmental delay
      compared with foster caregivers (95% CI 0.1, 0.4). Results suggest that caregiver
      identification of developmental delays is specific but not sensitive, and that
      foster caregivers were more likely to identify a child with a developmental delay
      compared with in-home caregivers. Policy implications include improving
      educational programs regarding child development and developmental services for
      foster, kinship, as well as in-home caregivers in the hopes of increasing
      sensitivity of caregiver identification of developmental delays for the
      population of young children involved with CW.

PMID- 16906008
TI  - Language use in females with fragile X or Turner syndrome during brief initial
      social interactions.
AB  - Fragile X and Turner syndromes are associated with risk of atypical social
      function. We examined language use, including normal and atypical speech, during
      initial social interactions among participants engaged in a brief social role
      play with an unfamiliar adult. There were 27 participants with Turner syndrome,
      20 with fragile X syndrome and 28 in an age-matched comparison group. Females
      with fragile X did not exhibit more abnormal language, but exhibited less of what
      is typical during initial interactions. Overall rates of dysfluencies did not
      differ, although females with fragile X made more phrase repetitions. Females
      with Turner syndrome had no language use abnormalities. Our findings suggest that
      language use may influence social function in females with fragile X syndrome and
      that such language characteristics may be observed in the context of brief
      encounters with an unfamiliar adult.

PMID- 16906009
TI  - The influence of temperament on weight gain in early infancy.
AB  - Difficult temperament has been associated with fast weight gain and slow weight
      gain, although the latter mostly in referred subjects studies in late infancy.
      The current study set out to investigate early weight gain in relation to all
      domains of temperament in a community-screened sample. Weight gain from birth to
      8 weeks was assessed in 75 infants recruited from local health care clinics who
      had demonstrated slow, average, or fast weight gain. Mothers completed a
      temperament questionnaire and a 2-day diary recording infant behaviors (sleeping,
      feeding, fussing, and crying). Weight gain from birth to 8 weeks was
      significantly related to infant temperament. The temperament dimension fear
      (acceptance or rejection of new objects or persons) was related to slow weight
      gain and the temperament dimension distress to limitations (negative emotionality
      and the infant's reaction to frustrating situations) was related to fast weight
      gain. The regression model explained 59% of the variance, with the temperament
      dimensions explaining 11%. Diary data showed that infants who scored high on fear
      tended to cry a lot, while infants with high scores on distress to limitations
      tended to sleep less and cry and fuss more. The results emphasize that different
      temperament domains influence slow and fast weight gain. In addition, the data
      suggest that infant temperament plays a part in physical development in early
      infancy.

PMID- 16906010
TI  - Commentary on Hooper et al.

PMID- 16906011
TI  - Chronic constipation, atypical eating pattern, weight loss, and anxiety in a 19
      year old youth.

PMID- 16906012
TI  - Suffering in silence: why a developmental psychopathology perspective on
      selective mutism is needed.
AB  - A developmental psychopathology perspective is offered in an effort to organize
      the existing literature regarding the etiology of selective mutism (SM), a
      relatively rare disorder in which a child consistently fails to speak in 1 or
      more social settings (e.g., school) despite speaking normally in other settings
      (e.g., home). Following a brief description of the history, prevalence, and
      course of the disorder, multiple pathways to the development of SM are discussed,
      with a focus on the various genetic, temperamental, psychological, and
      social/environmental systems that may be important in conceptualizing this
      unusual childhood disorder. The authors propose that SM develops due to a series
      of complex interactions among the various systems reviewed (e.g., a strong
      genetic loading for anxiety interacts with an existing communication disorder,
      resulting in heightened sensitivity to verbal interactions and mutism in some
      settings). Suggestions are provided for future longitudinal, twin/adoption,
      molecular genetic, and neuroimaging studies that would be particularly helpful in
      testing the pathways perspective on SM.

PMID- 16906015
TI  - Catatonia under treatment with risperidone.

PMID- 16906017
TI  - The mu-opioid receptor gene polymorphism 118A>G depletes alfentanil-induced
      analgesia and protects against respiratory depression in homozygous carriers.
AB  - AIM: To investigate whether OPRM1 118A>G polymorphism affects analgesic and
      respiratory depressive effects of alfentanil and assess its role for the
      therapeutic range of alfentanil. METHODS: In an open-label, single-occasion
      design, 10 non-carriers, four heterozygous and six homozygous carriers of the
      variant OPRM1 118G allele received a computerized infusion of alfentanil to
      achieve target effect-site concentrations of 0, 33.33, 66.67 and 100 ng/ml. At
      each concentration level, analgesia was assessed by means of electrically and
      chemically induced pain, and respiratory depression was quantified by hypercapnic
      challenge and breathing frequency. RESULTS: The relationship between the percent
      change of tolerance to electrical stimuli and measured alfentanil concentrations,
      described by power models, was flatter in carriers of the 118G variant allele
      than in non-carriers, indicating decreased opioid analgesia (P<0.05). For
      chemically induced pain, a flatter analgesia versus concentration relationship
      was found only for homozygous carriers of the 118G allele (P<0.05). The
      relationship between the percent changes in respiratory parameters was
      significantly flatter (P<0.01) only in homozygous carriers as compared to
      heterozygous carriers and non-carriers of the 118G allele. Higher alfentanil
      concentrations were needed in homozygous carriers as compared to wild-type
      subjects (2-4 times) to produce the same degree of analgesia, whereas 10-12 times
      higher alfentanil concentrations were needed to produce the same degree of
      respiratory depression. CONCLUSION: OPRM1 118A>G polymorphism affects both
      analgesic and respiratory depressive effects of alfentanil. However, while the
      analgesic effects are already partly decreased in heterozygous carriers,
      depending on the pain model, the respiratory depressive effects are decreased in
      homozygous carriers of the variant 118G allele. The therapeutic range of
      alfentanil was only broadened in homozygous carriers.

PMID- 16906016
TI  - HLA-G 14-bp polymorphism regulates the methotrexate response in rheumatoid
      arthritis.
AB  - OBJECTIVE: Methotrexate (MTX) represents the antirheumatic drug mainly used in
      rheumatoid arthritis (RA). HLA-G antigens are inducible nonclassical major
      histocompatibility complex class Ib molecules important for maintaining anti
      inflammatory conditions. The HLA-G gene is characterized by a deletion/insertion
      polymorphism of 14 bp that controls specific mRNA stability and protein levels.
      It has been reported that MTX therapy mediates an increase of interleukin-10
      producing cells. This cytokine up-regulates HLA-G expression. For this, we tested
      the hypothesis of an MTX-mediated HLA-G production and the possible relationship
      with the HLA-G 14-bp polymorphism. METHODS: Peripheral blood mononuclear cells
      from healthy individuals and non-MTX-treated RA patients were activated with
      different MTX concentrations, and soluble HLA-G (sHLA-G) and interleukin-10
      production was investigated by specific immunoenzymatic assay. HLA-G 14-bp
      polymorphism genotyping was performed in healthy individuals and RA patients,
      defined as 'responders' and 'nonresponders' to the MTX therapy. RESULTS: MTX
      activation induces the production of sHLA-G molecules. A significant association
      was observed between the highest sHLA-G1 concentrations and the -14/-14 bp
      genotype. The analysis of the HLA-G 14-bp polymorphism in MTX-treated RA patients
      has confirmed an increase of the -14/-14 bp genotype in the responder group
      (chi=6.12, P=0.02; chi test) (odds ratio=2.46 (95% confidence interval, 1.26
      4.84) P=0.009; logistic regression model). CONCLUSION: Our results propose that
      the MTX induces the production of the anti-inflammatory sHLA-G molecules that
      concur with the therapy response. Furthermore, the association between -14/-14 bp
      genotype and MTX clinical outcome proposes this polymorphism as a therapy marker
      in the early phases of the disease.

PMID- 16906018
TI  - CYP3A5 genotype has significant effect on quinine 3-hydroxylation in Tanzanians,
      who have lower total CYP3A activity than a Swedish population.
AB  - OBJECTIVES: To study the correlation between CYP3A5 genotype and quinine 3
      hydroxylation in black Tanzanian and Swedish Caucasians as well as to investigate
      the interethnic differences in CYP3A activity between the two populations.
      METHODS: Tanzanian (n=144) and Swedish (n=136) healthy study participants were
      given a single oral 250 mg dose of quinine hydrochloride and a 16-h post-dose
      blood sample was collected. The metabolic ratio of quinine/3-hydroxyquinine was
      determined in plasma by high-performance liquid chromatography. All the
      participants were genotyped for the known mutations of CYP3A5, which are relevant
      for the respective population. Correlation between quinine metabolic ratio and
      CYP3A5 genotype as well as the interethnic difference in CYP3A activity between
      the two populations was studied. RESULTS: Tanzanians had significantly higher
      (P<0.0001) mean quinine metabolic ratio (9.5+/-3.5) than Swedes (7.6+/-3.1). As
      expected, the frequency of high CYP3A5 expression alleles was higher in
      Tanzanians (51%) than in Swedes (7%). The mean+/-SD quinine metabolic ratio
      (10.7+/-3.9) in Tanzanians homozygous for low CYP3A5 expression gene was
      significantly higher than the corresponding mean metabolic ratio in participants
      heterozygous (9.5+/-3.3; P=0.02) or homozygous (8.1+/-3.1; P=0.002) for high
      expression CYP3A5 alleles, respectively. A tendency to higher quinine metabolic
      ratio in Swedes with low expression alleles compared with those with one or two
      high expression alleles was observed. Tanzanians homozygous for low CYP3A5
      expression gene (i.e. only CYP3A4 is expressed) had significantly (P<0.0001)
      higher quinine metabolic ratio (10.7+/-3.9) than corresponding Swedes (7.7+/
      3.1). CONCLUSIONS: Clear interethnic differences were observed in the activity of
      CYP3A between Tanzanians and Swedes. A significant association is noted between
      CYP3A5 genotype and quinine 3-hydroxylation in Tanzanians, indicating a
      significant contribution of CYP3A5 to total 3A activity. The CYP3A4 catalyzed
      hydroxylation of quinine (two low CYP3A5 expression alleles) was lower in
      Tanzanians than in Swedes.

PMID- 16906019
TI  - Transcriptomic and phylogenetic analysis of Kpna genes: a family of nuclear
      import factors modulated in xenobiotic-mediated liver growth.
AB  - OBJECTIVES: We have identified a member of the karyopherin (importin) alpha
      family of nuclear import factors as being modulated in rat liver following
      exposure to the hypolipidaemic and liver growth agent Wy-14,643. To examine the
      hypothetical role of this protein family as a checkpoint in receptor-mediated
      signalling, we characterized the rat karyopherin alpha (Kpna) gene family and
      present cDNA sequences and gene structures for all six rat Kpna genes. Further,
      we have assembled a comprehensive panel of Kpna coding regions from a range of
      metazoa, which we have subjected to phylogenetic analysis: This represents by far
      the most complete phylogenetic study of metazoan karyopherins, including several
      evolutionary intermediates not previously examined. The phylogeny reveals three
      Kpna subfamilies with distinct, conserved gene structures, shedding light on the
      evolutionary origins of this multigene family in metazoa. METHODS AND RESULTS:
      Using quantitative PCR, we have analysed Kpna transcript levels in 44 rat
      tissues; Kpna transcripts show a wide variation in their distribution both in
      absolute and relative terms, suggestive of specialized roles for each member. We
      also demonstrate that Kpna genes are regulated in rat liver and isolated
      hepatocytes in a xenobiotic-specific manner for a number of chemically distinct
      liver growth agents. CONCLUSIONS: In light of the crucial role of nuclear import
      in mediating the genomic changes elicited through nuclear receptor activation, we
      postulate that changes in the levels of specific karyopherins alpha during
      xenobiotic-mediated liver growth represent an important component of the cellular
      response to the external stimuli that trigger these events.

PMID- 16906020
TI  - Cyp3A4, Cyp3A5, and MDR-1 genetic influences on tacrolimus pharmacokinetics in
      renal transplant recipients.
AB  - OBJECTIVE: The immunosuppressive drug tacrolimus requires strict therapeutic
      monitoring due to its narrow therapeutic index and great inter-individual
      variability. Cytochrome P450 3A4 (Cyp3A4) and Cyp3A5 are the most important
      contributors to tacrolimus metabolism while the P-glycoprotein pump (MDR-1)
      modulates its bioavailability. The objective was to investigate the association
      between Cyp3A4, Cyp3A5, and MDR-1 polymorphisms and tacrolimus pharmacokinetics
      in the early period after renal transplantation. METHODS: Forty-four renal
      transplant recipients were genotyped for 8 Cyp3A4, 7 Cyp3A5, and 5 MDR-1 genetic
      variants affecting the proteins' expression and/or function. Dose-adjusted
      tacrolimus though levels were determined during the first week after
      transplantation and correlated with corresponding genotype. RESULTS: We found no
      correlation between Cyp3A4 polymorphism and tacrolimus pharmacokinetics. Patients
      who do not carry both Cyp3A5*3 alleles achieved lower mean dose-adjusted
      tacrolimus blood concentrations (p<0.001) and needed a longer time to reach the
      target concentration (10-12 ng/ml; p<0.001) compared to Cyp3A5*3 homozygotes.
      Patients with less than three copies of MDR-1 (T-129C, C3435T and G2677T)
      polymorphisms, associated with reduced expression of P-glycoprotein, had also
      lower dose-adjusted tacrolimus blood concentrations compared to patients having
      equal to or greater than three copies of MDR-1 genetic variants (P=0.003). There
      was no difference in the rate of biopsy-confirmed acute rejection among groups
      during the first 3 months after transplantation. CONCLUSION: The complete absence
      of Cyp3A5*3 allele and the accumulation of less than three copies of MDR-1 (T
      129C, C3435T and G2677T) polymorphisms are associated with lower tacrolimus blood
      levels identifying these genotypes as markers for patients requiring higher
      tacrolimus doses.

PMID- 16906021
TI  - Identification and functional significance of SNPs underlying conserved haplotype
      frameworks across ethnic populations.
AB  - BACKGROUND: The study of genetic variation will promote our understanding of the
      differential predisposition to common diseases and variation in drug responses of
      individuals and ethnic populations. Such genetic variation is intrinsically
      structured into blocks of haplotypes in populations. Therefore, a comprehensive
      haplotype map based on the most abundant form of genetic variation, single
      nucleotide polymorphisms, will be useful. At the present time, however, our
      knowledge of the similarities and differences of haplotype structure among
      different ancestral populations is still inadequate. METHODS: To determine
      whether common underlying haplotype patterns existed across ethnic populations,
      we analyzed data derived from African and European Americans for twenty-two genes
      spanning a total of 516 kb and the HapMap ENCODE data across 500 kb on chromosome
      2p16.3 from three major world populations. RESULTS AND CONCLUSIONS: We observed
      that strong pairwise linkage disequilibrium (LD) between SNPs selected from
      populations having African ancestry was highly conserved across other non-African
      populations. Common haplotypes described by these LD-selected SNPs demonstrated a
      simple evolutionary structure with up to three major frameworks, which were
      likely ancestral backgrounds upon which more recent mutations have been
      superimposed. Also, haplotype block boundaries defined in populations having
      African ancestry revealed completely concordant recombinant haplotypes across all
      populations, providing a consistent definition of block structure. Finally, a
      large fraction of regulatory polymorphisms described in the literature appeared
      to tag these conserved haplotype frameworks, strongly suggesting their
      significance for disease association and pharmacogenetic studies.

PMID- 16906022
TI  - Pharmacogenetics of SLCO1B1 gene and the impact of *1b and *15 haplotypes on
      irinotecan disposition in Asian cancer patients.
AB  - OBJECTIVE: To investigate the pharmacogenetic effect of SLCO1B1 *1a, *1b, *5 and
      *15 polymorphisms on irinotecan disposition in Asian cancer patients.
      EXPERIMENTAL DESIGN: Irinotecan was administered over 90 min either at 100 mg/m
      on days 1, 8 and 15 with the regimen being repeated every 28 days (N=28) or at
      375 mg/m once every three weeks (N=43). Plasma concentrations of irinotecan, 7
      ethyl-10-hydroxycamptothecin and 7-ethyl-10-hydroxycamptothecinG were analysed
      after the first dose of the first cycle and the influence of SLCO1B1 *1a, *1b, *5
      and *15 polymorphisms on the disposition of irinotecan and its metabolites were
      evaluated. RESULTS: Pharmacokinetic parameters were obtained from 71 cancer
      patients. Genotypic-phenotypic correlates showed the clearance of irinotecan to
      be 3-fold lower in patients carrying the *15 haplotype than cancer patients with
      the reference genotype *1a/*1a (9.57+/-3.15 vs. 28.86+/-10.97 l/h/m; P=0.001).
      The area under the plasma concentration-time curve from zero to infinity and
      normalized by dose and body surface area (AUC0-nf/dose/BSA) were significantly
      higher in patients harbouring the *15 haplotype than patients with the reference
      genotype for irinotecan (39.27+/-15.17 vs. 17.32+/-6.30 h/m; P=0.003) and 7-ethyl
      10-hydroxycamptothecin (1.28+/-0.53 vs. 0.69+/-0.32 h/m; P=0.021). The exposure
      levels to 7-ethyl-10-hydroxycamptothecinG also showed a statistically significant
      trend among the SLCO1B1 haplotype pairs, being approximately 10-fold lower in
      patients with *15 haplotype than with patients harbouring the reference genotype
      (3.57+/-1.95 vs. 12.0+/-6.09 h/m; P=0.016). CONCLUSION: These findings suggest
      that (1) SLCO1B1 haplotypes may have a significant influence on the disposition
      of irinotecan and its metabolites in Asian cancer patients, and (2) patients with
      SLCO1B1*15 haplotype may be susceptible to increased sensitivity to irinotecan,
      which may manifest itself either by increased efficacy or toxicity or both owing
      to the increased exposure levels to 7-ethyl-10-hydroxycamptothecin.

PMID- 16906023
TI  - Janus tyrosine kinases and signal transducers and activators of transcription
      regulate critical functions of T cells in allograft rejection and transplantation
      tolerance.
AB  - Full activation of T cells requires three sequential signals. Engagement by
      antigen presenting cells (APC) delivers signals 1/2, whereas signal 3 is
      delivered by multiple cytokines to regulate the immune homeostasis by influencing
      proliferation, differentiation, and survival/death. Signaling by cytokines acting
      through their receptors is delivered by two major molecular families, namely
      Janus tyrosine kinases (Jaks) and signal transducers and activators of
      transcription (Stats). Findings obtained from mice genetically deficient in Jaks
      and Stats suggest that these molecules may serve as therapeutic targets to
      prevent allograft rejection, induce transplantation tolerance, and inhibit
      autoimmune disease and lymphoid-derived tumors. This review describes the role of
      Jak tyrosine kinases and Stat transcription factors and their putative function
      in regulating T and B cell activity.

PMID- 16906024
TI  - Liver transplantation with "rescue organ offers" within the eurotransplant area:
      a 2-year report from the University Hospital Essen.
AB  - Liver transplantation (LTx) is the only treatment for patients with end-stage
      liver failure. This report focuses on 45 deceased donor liver allografts
      allocated through Eurotransplant as "rescue offers," which were accepted and
      subsequently transplanted at our center over a two-year period. These organs had
      been officially offered to and rejected by other transplant centers a total of
      162 times prior to our acceptance. Primary nonfunction was observed in six
      patients. Two of them died and four were retransplanted. Overall patient survival
      was 84.4%. LTx with such "rescue organs" constitutes an additional transplant
      option and a safe mechanism to "rescue" organs within Eurotransplant.

PMID- 16906025
TI  - Commentary for macroencapsulation protects against sensitization after allogeneic
      islet transplantation in rats.

PMID- 16906026
TI  - Therapeutic approaches to counteract immediate blood-mediated inflammatory
      reaction in islet transplantation.

PMID- 16906027
TI  - Allosensitization does not increase the risk of xenoreactivity to alpha1,3
      galactosyltransferase gene-knockout miniature swine in patients on
      transplantation waiting lists.
AB  - BACKGROUND: The recent availability of alpha1,3-galactosyltransferase knockout
      (GalT-KO) miniature swine has eliminated anti-Gal antibodies as the major barrier
      to xenotransplantation, potentially bringing this modality closer to clinical
      application. Highly-allosensitized patients, who have poor prospects of receiving
      a suitable cross-match negative human organ, might be the first patients to
      benefit from xenotransplantation of porcine organs. However, concerns exist
      regarding cross-reactivity of alloreactive anti-human leukocyte antigen (HLA)
      antibodies against xenogeneic swine leukocyte antigen (SLA) antigens. We have
      investigated this question using sera from such patients on GalT-KO target cells.
      METHODS: Using flow cytometry and complement-dependent cytotoxicity (CDC) assays,
      we have tested a panel of 88 human serum samples from patients awaiting cadaveric
      renal allotransplantation for reactivity against: 1) human; 2) standard miniature
      swine; and 3) GalT-KO peripheral blood lymphocytes (PBL) and cultured endothelial
      cells. RESULTS: Anti-swine IgM and IgG antibody binding, as well as CDC, were
      significantly attenuated on GalT-KO versus standard swine. No correlation was
      found between the degree of anti-human panel reactive antibodies (PRA) and
      xenoreactivity against either standard or GalT-KO miniature swine. Treatment of
      sera with dithiothreitol (DTT) showed that the majority of remaining
      lymphocytotoxicity against GalT-KO swine was mediated by preformed IgM
      antibodies. Patients with high alloreactivity but low anti-GalT-KO xenoreactivity
      were readily identified. CONCLUSIONS: Highly allosensitized patients awaiting
      renal transplants appear to be at no increased risk of xenosensitization over
      their non-sensitized cohorts, and could therefore be candidates for
      xenotransplantation using GalT-KO swine donors.

PMID- 16906028
TI  - Novel application of ProteinChip technology exploring acute rejection markers of
      rat small bowel transplantation.
AB  - BACKGROUND: Because no biomarker that reflects small bowel allograft rejection is
      available, we applied surface-enhanced laser desorption/ionization time-of-flight
      mass spectrometry (SELDI-TOF MS) to develop noninvasive markers required for
      routine diagnosis. METHODS: Heterotopic small bowel transplantation (SBT) was
      performed in rats, and they were divided into four experimental groups: sham
      operated rats (sham), syngeneic transplants (syngeneic), allogeneic transplants
      (allogeneic), allogeneic transplants received FK506 (allo+FK). Plasma samples
      were analyzed with SELDI ProteinChip arrays to detect peaks that predominated in
      the allogeneic model. Possible biomarkers were identified in combination with
      SELDI retentate chromatography mass spectrometry (RCMS) and matrix-assisted laser
      desorption/ionization mass spectrometry (MALDI-MS). The identified protein was
      further analyzed by immunohistochemistry. RESULTS: An increase in the level of a
      14.8-kDa protein, identified as lysozyme, was observed specifically in the plasma
      of the allogeneic group; the levels of this protein remained unchanged in the
      plasma of the other groups. On the other hand, the levels of a 10.1-kDa and a
      13.0-kDa protein, identified as migration inhibitory factor-related proteins
      (MRP), MRP-8 and MRP-14, respectively, began to increase from an early stage of
      acute rejection. We also observed that lysozyme-positive macrophages had strongly
      infiltrated the lamina propria during acute rejection. CONCLUSIONS: We identified
      three plasma proteins-MRP-8, MRP-14, and lysozyme-that increased during small
      bowel allograft rejection. The identified proteins appeared to be markers for
      inflammation associated with allograft rejection. This proteomic approach will be
      useful for the identification of candidate biomarkers.

PMID- 16906029
TI  - Procurement of the human pancreas for pancreatic islet transplantation from
      marginal cadaver donors.
AB  - BACKGROUND: Recent advances in pancreatic islet transplantation (PIT) have
      contributed significantly to the treatment of patients with type 1 diabetes. The
      specific aim of this study was to develop an effective technique for the
      procurement of pancreas for PIT from nonheart-beating-donor (NHBDs). METHODS:
      Between January 2004 and August 2004, eight human pancreata were procured and
      processed for isolation of islets at a cell processing center. After confirmation
      of brain death status, a double balloon catheter was inserted to prevent warm
      ischemic damage to the donor pancreas by using an in situ regional organ cooling
      system that was originally developed for procurement of kidneys. The catheter
      position of the cooling system was modified specifically for the pancreas and
      kidney. Furthermore, we worked in cooperation with a kidney procurement team to
      protect the pancreas during kidney procurement. RESULTS: Warm ischemic time could
      be controlled with the modified in situ regional cooling system at 3.0 +/- 0.8
      min (mean +/- SE). The operations for procurement of the kidneys and pancreata
      lasted 45.6 +/- 3.6 min and 10.6 +/- 1.8 min, respectively. Islet yield per
      isolation was 444,426 +/- 35,172 IE (islet equivalent). All eight cases met the
      criteria for PIT based on the Edmonton protocol. CONCLUSION: We developed a novel
      procurement technique in cooperation with our kidney procurement team. This
      protocol for the procurement of pancreas and kidney from a NHBD enabled us to
      transplant islets into a type 1 diabetic patient and kidney into a renal failure
      patient.

PMID- 16906030
TI  - Dog leukocyte antigen-haploidentical stem cell allografts after anti-CD44 therapy
      and nonmyeloablative conditioning in a preclinical canine model.
AB  - BACKGROUND: We previously described a reduced-intensity hematopoietic cell
      transplantation (HCT) regimen in dog leukocyte antigen (DLA)-haploidentical
      littermate recipients consisting of 450 cGy total body irradiation (TBI) and anti
      CD44 monoclonal antibody (mAb) S5 before and mycophenolate mofetil
      (MMF)/cyclosporine (CSP) after HCT. METHODS: We tested a nonmyeloablative regimen
      of mAb S5 and 200 cGy TBI with postgrafting MMF/CSP in 44 DLA-haploidentical
      recipients using eight different regimens. Ten dogs also received escalating
      doses of donor lymphocyte infusion (DLI) alone or with pentostatin to convert to
      complete donor chimerism. RESULTS: All dogs achieved initial engraftment between
      one to two weeks after HCT with peripheral blood mononuclear cell (PBMC) donor
      chimerism ranging from 2% to 98% (median 37%) on day +35. Twenty-five (57%) dogs
      rejected their donor grafts at a median of seven (range; 1-19) weeks after HCT.
      Low levels of PBMC donor chimerism at three weeks predicted graft rejection. DLI
      neither facilitated conversion to full donor chimerism after HCT nor prevented
      rejection. Higher total nucleated cells, CD4+, CD8+, and CD14+ cell subset
      numbers in the PBMC graft were associated with stable full donor engraftment.
      Dogs given higher cell subset doses of infused PBMC achieved longer duration of
      mixed chimerism. CONCLUSIONS: Nonmyeloablative conditioning with 200 cGy TBI and
      anti-CD44 mAb was sufficient for initial uniform engraftment across DLA haplotype
      mismatched barriers. However, sustained donor engraftment was seen in only 43% of
      recipients. Graft composition and donor-dominant chimerism early after HCT may be
      the most important factors for sustained donor engraftment.

PMID- 16906031
TI  - Revascularization of transplanted pancreatic islets following culture with
      stimulators of angiogenesis.
AB  - BACKGROUND: Insufficient revascularization of transplanted islets may result in
      chronic hypoxia and loss of islet function. This study investigated whether
      simple culture of islets with angiogenic substances before transplantation could
      improve graft revascularization. METHODS: Mouse islets were cultured with
      vascular endothelial growth factor (VEGF; 20 ng/ml), fibroblast growth factor 2
      (FGF-2; 20 ng/ml) or matrix metalloproteinase 9 (MMP-9; 1 mug/ml). Thereafter,
      250 islets were implanted beneath the renal capsule of syngeneic C57Bl/6 mice.
      One month posttransplantation, blood flow (laser-Doppler flowmetry), oxygen
      tension (Clark microelectrodes), and vascular density were measured and
      correlated to graft function. RESULTS: Treatment of islets with VEGF during
      culture caused islet blood vessels to dilate, whereas FGF-2 treatment induced
      endothelial cell proliferation. However, the number of capillaries in both cases
      decreased during culture. When investigated one month posttransplantation, both
      VEGF and FGF-2 pretreated islets had similar or worse vascular engraftment when
      compared to transplanted control islets. MMP-9 pretreatment of islets increased
      vascular density, blood flow and oxygen tension within the grafts. Animals
      receiving MMP-9 pretreated islets returned, however, more slowly to normoglycemia
      than control animals, and performed worse than controls in a glucose tolerance
      test one month posttransplantation. CONCLUSIONS: Treatment of islets during
      culture with VEGF or FGF-2 changed the islet vascular phenotype, but capillaries
      were still lost. Notably, the number of capillaries in the grafted islets one
      month posttransplantation was in all cases strikingly similar to that observed
      prior to transplantation. MMP-9 pretreatment of islets elicited an angiogenic
      response, which improved revascularization of the transplanted islets.

PMID- 16906032
TI  - Superiority of pediatric en bloc renal allografts over living donor kidneys: a
      long-term functional study.
AB  - BACKGROUND: Growing waiting list for kidney transplantation in the United States
      makes it imperative to expand donor pool to use of pediatric kidneys. Because en
      bloc pediatric kidneys double nephron numbers, it would be interesting to learn
      how they fare compared to living donor kidneys long term. METHODS: Retrospective
      chart review was performed on all 72 pediatric en bloc and 75 live adult donor
      kidney recipients transplanted between January 1990 and December 2001. Long term
      graft function was assessed with glomerular filtration rate (GFR) using the
      abbreviated modification of diet in renal disease (MDRD) formula. RESULTS:
      Pediatric donor was 16.9 +/- 11.2 months old and weighed 10.7 +/- 3.8 kg. Nine en
      bloc kidneys thrombosed at a mean of 4.2 days posttransplantation. Proteinuria
      was detected later posttransplantation in en bloc group (45.6 +/- 33.6 months vs.
      23.4 +/- 16.3 months, P = 0.002). Pediatric en bloc recipients had significantly
      higher GFR up to 8 years posttransplantation. One-year graft survival was
      significantly better in live donor group (93.3% vs. 81.9%, P = 0.041) but five
      year graft survival rates were similar (86.7% vs. 76.3%, P = 0.125). One-year and
      five-year patient survival rates were similar between en bloc and live donor
      groups (97.3% vs. 98.6%, P = 0.585 and 94.6% vs. 93.0%, P = 0.688, respectively).
      CONCLUSION: Early postoperative graft thrombosis remain a challenge with
      pediatric en bloc renal transplants, but once the allografts survive early
      postoperative course, they provide better long-term function than living donor
      kidney transplants. In order to alleviate burden on waiting list, pediatric en
      bloc kidneys should be transplanted more often when available.

PMID- 16906033
TI  - The predictive value of soluble major histocompatibility complex class I chain
      related molecule A (MICA) levels on heart allograft rejection.
AB  - BACKGROUND: Recently the presence of a soluble form of major histocompatibility
      complex class I chain-related molecule A (sMICA) has been detected in the sera of
      patients with tumors. Shedding of sMICA by tumor cells downregulates NKG2D
      mediated antitumor immunity. The aim of this investigation was to study the
      possible involvement of sMICA in the allograft acceptance after heart
      transplantation (HTX). METHODS: We monitored the levels of sMICA by specific
      enzyme-linked immunosorbent assay (ELISA) in a total of 146 serum samples
      obtained from 34 heart transplantation patients followed up during the first year
      post-HTX. RESULTS: The persistence of sMICA expression was correlated with the
      clinical evolution of these patients. sMICA was detected in the serum of 21 of 34
      patients (61.70%) between 15 and 20 days after implantation and was practically
      absent in pretransplant serum samples. Twenty of these 21 patients (95.24%) with
      sMICA did not experience episodes of severe rejection during this period (P =
      0.0001), whereas sMICA was practically absent in patients with manifestations of
      severe acute rejection. The longitudinal study of these patients revealed that
      the presence of sMICA was consistently maintained in 75% of the patients with
      good graft status during the period of observation. CONCLUSION: This has led us
      to believe that the presence of levels of sMICA during the first year post-HTX
      may contribute to allograft acceptance. Additionally, functional studies indicate
      that sMICA downregulates NKG2D surface expression, which may lead to a functional
      impairment of cell-mediated cytolysis. These data suggest a significant
      correlation between the presence of sMICA and a lower incidence of rejection.

PMID- 16906034
TI  - High pretransplant parathyroid hormone levels increase the risk for graft failure
      after renal transplantation.
AB  - BACKGROUND: Calcium (Ca), phosphate (P), and parathyroid hormone (PTH) are
      important variables influencing the risk for cardiovascular disease in dialysis
      patients. We studied the influence of long-standing Ca-P disregulation on renal
      transplant survival. METHODS: Pretransplant PTH, Ca, P, total protein (TP),
      albumin, and alkaline phosphatase (AP) values were gathered in all 407 patients
      that received a renal transplant in our center between January 1, 2000 and July
      1, 2004. Other variables expected to influence the risks were included. RESULTS.
      In the Cox proportional hazards analysis the risk for graft failure censored for
      death was significantly influenced by pretransplant PTH concentration (P = 0.008)
      and donor type (P < 0.001). The influence of PTH on the risk for patient death
      was not significant. The risk for acute rejection was studied but PTH level did
      not have a significant influence on this risk (P = 0.055). The risk for delayed
      graft function was not influenced by PTH level. CONCLUSION: Serum PTH levels have
      an independent influence on the risk for graft failure censored for death.
      Efforts to improve calcium-phosphate-PTH homeostasis in patients on the waiting
      list for renal transplantation should be encouraged also to improve graft
      survival.

PMID- 16906035
TI  - Differences in proteinuria and graft function in de novo sirolimus-based vs.
      calcineurin inhibitor-based immunosuppression in live donor kidney
      transplantation.
AB  - BACKGROUND: Calcineurin inhibitor(CNI)-free protocols using sirolimus (SRL) in
      kidney transplantation have proven effective, although reports have linked SRL to
      proteinuria. We sought to investigate this link and its impact on graft function.
      METHODS: We retrospectively analyzed 184 live donor kidney transplant recipients
      who exclusively received de novo CNI-based (n = 106) or SRL-based (n = 78)
      regimens. Estimated glomerular filtration rate (GFR) and semi-quantitative
      dipstick proteinuria measurements were obtained at one, six, 12, and 24 months
      and six and 12 months, respectively. RESULTS: SRL-treated patients had higher
      frequencies of proteinuria (> or =1+) at 6 months (40.8% vs. 21.4%, P = 0.006)
      and 12 months (37.8% vs. 18.4%, P = 0.004) than those treated with CNI.
      Independent predictors of proteinuria at 12 months were GFR at one month (OR 0.62
      per 10 ml/min/1.73 m, P<0.001), delayed graft function (OR 11.5, P = 0.02), and a
      SRL-based regimen (OR 4.18, P=0.002). By univariable analysis, SRL vs. CNI
      patients had higher GFR at each point. SRL-treated patients without proteinuria
      had higher GFR at 12 months compared to CNI-treated patients with and without
      proteinuria (66 vs. 50 or 56 ml/min/1.73 m, P < 0.05). No difference in GFR was
      seen between SRL-treated patients with proteinuria vs. CNI-treated patients
      without proteinuria (57 vs. 56 ml/min/1.73 m, P > 0.05). Absence of proteinuria
      and a SRL-based regimen remained independently associated FS with higher GFR at
      12 months by multivariable analyses. CONCLUSIONS: De novo SRL-based
      immunosuppression is associated with a higher frequency of semi-quantitative
      proteinuria, however, estimated graft function at 1 year posttransplant remains
      superior to that of CNI-treated patients. Nevertheless, the long-term
      implications of these findings need to be determined.

PMID- 16906036
TI  - Anthracycline-based chemotherapy as first-line treatment in adults with malignant
      posttransplant lymphoproliferative disorder after solid organ transplantation.
AB  - BACKGROUND: Recommended first-line treatment for posttransplant
      lymphoproliferative disorder (PTLD) is reduction in immunosuppressive therapy,
      irrespective of histopathological type. Second-line treatment with chemotherapy
      is generally reserved for tumors that fail to respond to reduced
      immunosuppression. In view of the similarities between monomorphic PTLD and non
      Hodgkin's lymphoma in the general population, our policy is to treat monomorphic
      PTLD with anthracycline-based chemotherapy as first-line treatment. METHODS: A
      retrospective single-center analysis of 18 adults who developed PTLD following
      liver or kidney transplantation was undertaken, with particular emphasis on tumor
      histology, treatment received, and clinical outcome. RESULTS: Of the 18 patients
      with PTLD, 13 had high-grade malignant lymphoma on diagnostic biopsy and received
      anthracycline-based chemotherapy and reduction in immunosuppression as first-line
      therapy. Nine (69%) of the 13 patients achieved complete remission and eight
      (62%) remained in complete remission five years after diagnosis. There was no
      graft loss from rejection or drug toxicity. Four (22%) patients had polymorphic
      PTLD on diagnostic biopsy (of which two were re-classified as monomorphic) and
      one had a low-grade malignant lymphoma. All five patients were treated by
      reduction in immunosuppression without chemotherapy and were in complete
      remission at a median of two years after diagnosis. Overall, complete remission
      was seen in 14 out of 18 patients (78%) at one year following diagnosis.
      CONCLUSION: The use of anthracycline-based chemotherapy and reduction of
      immunosuppression as first-line treatment in adults with monomorphic PTLD is well
      tolerated and achieves sustained complete remission in around 70% of patients
      with a low risk of graft loss.

PMID- 16906037
TI  - Low incidence of BK virus nephropathy after simultaneous kidney pancreas
      transplantation.
AB  - BACKGROUND: BK virus renal allograft nephropathy (BKVAN) in the setting of
      simultaneous kidney-pancreas transplantation (SKPT) has been inadequately studied
      and reported. We analyzed our data on the incidence of BKVAN and its outcome in
      SKPT recipients at University of Pittsburgh Medical Center (UPMC) and affiliated
      centers and report significant differences compared to previous studies. METHODS:
      This study used retrospective review and case studies. RESULTS: A review of 243
      consecutive SKPT recipients from January 1, 1996 to December 31, 2004 identified
      seven cases (three females; ages = 23-54 yrs) of BKVAN following SKPT (incidence
      = 2.9%). The immunosuppressive protocols during this period were divided into:
      Period I (pre-August 2001) with no antibody induction and Period II (post-August
      2001) with alemtuzumab or antithymocyte globulin induction with steroid
      avoidance. One BKVAN case was diagnosed in Period II (incidence = 1.4%). Six of
      seven patients were treated with intravenous cidofovir (0.20-0.50 mg/kg) every
      two to four weeks over one to six months. Three patients lost the renal allograft
      8-22 months following diagnosis of BKVAN, whereas four patients had prolonged
      allograft survival. Pancreatic function was well preserved in five; one patient
      lost the pancreatic function due to surgical complications and one has had
      partial preservation. CONCLUSIONS: There was a relatively lower incidence of
      BKVAN among SKPT patients at our center. Although overall graft loss rate was
      comparable to other series, BKVAN patients had a slightly prolonged graft life.
      The BKVAN incidence was further reduced in patients receiving modified
      immunosuppression with antibody preconditioning. The underlying reasons may
      include less toxic immunosuppressive protocols, earlier diagnosis and the use of
      antiviral therapy.

PMID- 16906038
TI  - Steroid withdrawal for pancreas after kidney transplantation in recipients on
      maintenance prednisone immunosuppression.
AB  - Steroid withdrawal from patients taking prednisone for their renal allograft at
      the time of reinduction of immunosuppression for subsequent pancreas after kidney
      (PAK) transplantation has not been explored. Our expectation was that lymphocyte
      depletion, in conjunction with an augmentation of immunosuppression at the time
      of pancreas transplantation would protect the recipient from rejection of the
      renal allograft when chronic maintenance steroids are withdrawn. METHODS:
      Pancreas transplantation was performed using systemic venous drainage and enteric
      exocrine drainage. Regardless of preoperative immunosuppression, all patients
      received induction with antithymocyte globulin, a brief taper of intravenous
      solumedrol over four to five days, maintenance therapy with tacrolimus and
      sirolimus and either resumption of chronic maintenance steroids or complete
      withdrawal of steroids. RESULTS: A total of 30 PAK transplants were performed in
      29 recipients and divided into two groups: continuation of chronic steroids (n =
      10) or steroid-free (n = 19). One pancreas allograft was lost and there was a
      single mortality in the steroid free group. There was no significant difference
      in renal function or incidence of infections. CONCLUSION: Steroids can be safely
      withdrawn following pancreas after kidney transplantation for recipients already
      on maintenance prednisone in the setting of rabbit antithymocyte globulin
      induction and tacrolimus and sirolimus maintenance immunosuppression.

PMID- 16906039
TI  - Macroencapsulation protects against sensitization after allogeneic islet
      transplantation in rats.
AB  - BACKGROUND: The aim of this study was to evaluate the risks of sensitization by
      islet grafts encapsulated in a bilaminar immunoprotective membrane. METHODS: We
      studied five groups of Lewis rats: one control group (no islets), two groups that
      received free islets (200 or 1000 s.c.), and two groups that received
      encapsulated ones (200 or 1000 s.c.) from Dark Agouti (DA) rats. Four weeks
      later, abdominal heterotopic DA-heart transplantation was performed on the same
      recipients. The time-to-heart graft rejection was assessed by the cessation of
      heart contractions. Rejection was confirmed by histological examinations.
      Antidonor antibodies were determined by fluorescence activated cell sorter (FACS)
      analysis. RESULTS: The control animals had a mean heart graft survival of 6.4
      days. The free islet groups had significantly shorter heart graft survivals-i.e.,
      4.8 days (200 islets) and 1.0 day (1000 islets) (P < 0.001)-while those of the
      encapsulated islet groups were about the same as that of the control group-i.e.,
      6.4 days (200 islets) and 6.0 days (1000 islets). In the free islet groups, anti
      DA antibodies developed in 7/10 (200 islets) and 8/8 (1000 islets) animals after
      the islet transplantation. In the encapsulated groups, 1/10 (200 islets) and 3/8
      (1000 islets) animals developed anti-DA antibodies after these transplantations.
      All animals had anti-DA antibodies at the time of heart graft rejection. On
      histological examination all grafts showed various features of rejection.
      CONCLUSIONS: The bilaminar membrane protects against sensitization and prevents
      accelerated rejection of a subsequent vascularized graft, at least during the
      first month after the islet transplantation.

PMID- 16906040
TI  - Acute rejection and cardiac allograft vascular disease is reduced by suppression
      of subclinical cytomegalovirus infection.
AB  - BACKGROUND: Anticytomegalovirus (CMV) prophylaxis prevents the acute disease but
      its impact on subclinical infection and allograft outcome is unknown. We sought
      to determine whether CMV prophylaxis administered for three months after heart
      transplant would improve patient outcomes. METHODS: This prospective cohort study
      of 66 heart transplant recipients compared aggressive CMV prophylaxis (n = 21,
      CMV hyperimmune globulin [CMVIG] plus four weeks of intravenous ganciclovir
      followed by two months of valganciclovir); with standard prophylaxis (n = 45,
      intravenous ganciclovir for four weeks). Prophylaxis was based on pretransplant
      donor (D) and recipient (R) CMV serology: R-/D+ received aggressive prophylaxis;
      R+ received standard prophylaxis. Outcome measures were: CMV infection assessed
      by DNA-polymerase chain reaction on peripheral blood polymorphonuclear
      leukocytes, acute rejection, and cardiac allograft vascular disease (CAV)
      assessed by intravascular ultrasound. All patients completed one year of follow
      up. RESULTS.: CMV infection was subclinical in all but four patients (two in each
      group). Aggressively treated patients had a lower incidence of CMV infection (73
      +/- 10% vs. 94 +/- 4%; P = 0.038), and an independent reduced relative risk for
      acute rejection graded > or =3A (relative risk [95% CI] = 0.55 [0.26-0.96]; P =
      0.03), as compared with the standard prophylaxis group. Aggressively prophylaxed
      patients also showed a slower progression of CAV, in terms of coronary artery
      lumen loss (lumen volume change=-21 +/- 13% vs. -10+/-14%; P = 0.05); and vessel
      shrinkage (vessel volume change = -15 +/- 11% vs. -3 +/- 18%; P = 0.03).
      CONCLUSIONS: Prolonged (val)ganciclovir plus CMVIG reduces viral levels, acute
      rejection, and allograft vascular disease, suggesting a role for chronic
      subclinical infection in the pathophysiology of the most common diseases
      affecting heart transplant recipients.

PMID- 16906042
TI  - Suppressed splenocyte proliferation following a xenogeneic skin graft due to
      implanted biomaterials.
AB  - BACKGROUND: Immune system responses to antigens in the context of biomaterials
      are poorly understood. Biomaterial implantation results in an inflammatory
      reaction, which is anticipated to alter the adaptive immune response, in the case
      presented here, to a skin xenograft. Our earlier work showed unexpectedly low
      splenocyte proliferation following a xenogeneic cell implant in tandem with a
      biomaterial in the form of a microcapsule. Here we explore whether that effect
      was due to the cells or the biomaterial, and attempt to dissect the mechanism of
      immune deviation. METHODS: We assessed the immune response of Balb/c mice to
      hamster skin grafts accompanied by one of three implants: encapsulated xenogeneic
      cells; free cells accompanied by the same encapsulation biomaterials; and the
      encapsulation biomaterials without cells. Cells were encapsulated in a
      hydroxyethyl methacrylate-methyl methacrylate copolymer then embedded in an
      agarose gel. Splenocyte proliferation upon re-challenge in vitro, antibody titer
      in serum, and Th1/2 polarization (by cytokines in splenocyte challenge
      supernatants and antibody isotypes in serum) were measured. RESULTS: All skin
      grafts with encapsulation materials (even without cells) suppressed subsequent
      splenocyte proliferation at 10 days postimplant, although this effect disappeared
      by two months. In contrast, the antibody response was equal to or greater than
      that for a skin graft alone. Th1/2 polarization could not explain these
      observations because it did not correlate with the suppression of splenocyte
      proliferation. CONCLUSIONS: Implanted biomaterials caused nonspecific, transient
      suppression of splenocyte responses to hamster cells following hamster skin
      grafts, which is potentially important in the context of tissue engineering.

PMID- 16906041
TI  - Endothelin-mediated oncofetal fibronectin expression in chronic allograft
      nephropathy.
AB  - BACKGROUND: Chronic allograft nephropathy is a sclerotic process characterized by
      an increased extracellular matrix (ECM) protein deposition. Fibronectin (FN) is a
      major component of ECM. FN has been reported to undergo alternative splicing and
      produce several isoforms including the extra domain-B (ED-B) containing embryonic
      isoform. In the present study, we investigated ED-B FN expression in chronic
      allograft nephropathy and its relationship with endothelins (ET). METHODS: To
      establish chronic allograft nephropathy, allografts were performed between Fisher
      344 --> Lewis rats. Allograft recipients were then randomly divided into two
      groups, allografts and allografts treated with ET receptor antagonist bosentan.
      Lewis --> Lewis recipients were used as isograft controls. Grafts were harvested
      at 30, 90 and 140 days for histological and gene expression analyses with respect
      to ED-B FN, ET-1 and transforming growth factor-beta1 (TGF-beta1) mRNA. ED-B FN
      protein levels were assessed by immunohistochemical analysis. Additionally, we
      analyzed human renal allograft biopsies. RESULTS: Our data demonstrates that rat
      chronic allograft nephropathy is associated with progressive upregulation of ED-B
      FN mRNA and protein. ET-1 and TGF-beta1 mRNA were also upregulated. Treatment of
      allograft recipient rats with bosentan prevented upregulation of ED-B FN and TGF
      beta1. We further show that total FN, ED-B FN, ET-1 and TGF-beta1 mRNA expression
      were upregulated in human chronic allograft nephropathy specimens. CONCLUSION:
      Results obtained from both human and rat renal allograft tissues suggest that
      expression of ED-B FN is upregulated in chronic allograft nephropathy and such
      upregulation is mediated via ET-1 and its interaction with TGF-beta1.

PMID- 16906043
TI  - The influence of immunosuppressive drugs on T- and B-cell apoptosis via p53
      mediated pathway in vitro and in vivo.
AB  - BACKGROUND: This study was designed to assess the effects of calcineurin and
      inosine-5-monophosphate-dehydrogenase inhibitors on p53-mediated-apoptosis in T-
      and B-cells in vitro and in human heart-transplanted recipients (HTx-R). METHODS:
      For in vitro experiments, peripheral blood from healthy volunteers was collected
      and treated either with 1 microM cyclosporin A (CsA; n = 6), 10 microM
      mycophenolic acid (MPA; n = 6) or 100 nM tacrolimus (TRL; n = 6). For the second
      part, peripheral blood was collected from HTx-R undergoing CsA-MPA (n = 11) or
      TRL-MPA (n = 11) therapy before (0 hr) and after (2 hr) acute drug application
      and from healthy volunteers (n = 11) without drug therapy. Whole blood (part 1+2)
      was stimulated (24 hr) with eight different concentrations of actinomycin-D (0
      800 nM), an apoptosis inductor acting via p53-pathway. Apoptotic lymphocytes were
      measured by TUNEL and expression of Annexin-V using FACS. Drug effects were
      calculated by taking the effects of actinomycin-D as baseline values. RESULTS: In
      vitro drug treatment with CsA, MPA, and TRL significantly (P < 0.05) decreased
      the apoptotic effect of actinomycin-D in T-cells in a noncompetitive manner. In
      HTx-R undergoing drug therapy, there was a similar antiapoptotic effect observed
      in both T- and B-cells (P < 0.05). Differences between 0 hr and 2 hr after acute
      drug application did not exist. Apoptosis induced by actinomycin-D can be
      completely blocked by caspase-inhibitor zVAD-FMK. CONCLUSION: Our results suggest
      that, in vitro and in HTx-R, an inhibition of calcineurin and inosine-5
      monophosphate-dehydrogenase by CsA, TRL, or MPA lead to an inhibition of T-and B
      cell apoptosis via p53-pathway. This assay may be helpful to provide insights
      into mechanisms of immunosuppressive drugs in regulation of apoptosis in
      lymphocytes.

PMID- 16906044
TI  - The transgenic expression of human CD39 on murine islets inhibits clotting of
      human blood.
AB  - Platelet activation is believed to play an important role in the triggering of
      thrombosis of human blood by pig islets. We used a transgenic mouse model to
      investigate whether overexpression of CD39 (ecto nucleoside triphosphate
      diphosphohydrolase 1 [ENTPD1], EC 3.6.1.5), an ectonucleotidase that degrades the
      platelet agonists ATP, could interfere with this process. Islets isolated from
      CD39 transgenic mice showed 2.4-fold higher NTPDase activity than wild-type
      controls. When incubated with human blood, these islets significantly delayed
      clotting time compared to wild type islets (7.9 +/- 0.89 min versus 4.3 +/- 0.77
      min, P = 0.007). Importantly, expression of human CD39 in the islets of
      transgenic mice had no deleterious effect on glucose metabolism. These results
      suggest that transgenic expression of human CD39 does not interfere with islet
      function and may be a useful strategy to inhibit thrombosis induced by
      intraportal administration of islet xenografts.

PMID- 16906046
TI  - Delayed gastric ulcer healing associated with sirolimus.

PMID- 16906048
TI  - Tolerance to organ grafts in pigs.

PMID- 16906045
TI  - Poor prediction of the glomerular filtration rate using current formulas in de
      novo liver transplant patients.
AB  - The utility of formulas estimating glomerular filtration rate (GFR) in liver
      transplant patients has not been well described. The purpose is to determine the
      correlation between the radionuclide GFR (rGFR) with formulas commonly used to
      estimate GFR. This study represented a secondary outcome measure of a multicenter
      randomized trial comparing the effectiveness of two immunosuppressive regimens in
      adult liver transplant patients (n=148). A total of 68 rGFR were measured, 33 at
      baseline and at 35 at three months after transplantation. GFR was estimated using
      1/Scr and Cockcroft-Gault, MDRD, and Nankivell equations. At both time points
      assessed, all correlations with rGFR were poor: 1/Scr (r: 0.17 and 0.25),
      Cockcroft-Gault (r: 0.31 and 0.35), MDRD (r: 0.27 and 0.35), and Nankivell (r:
      0.11 and 0.20). Accepted formulas to estimate GFR correlate poorly with rGFR
      during the first three months after liver transplantation. Recalibration of these
      formulas is required to improve the estimation of GFR in liver transplant
      patients.

PMID- 16906050
TI  - Genomics and proteomics in epidemiology: treasure trove or "high-tech stamp
      collecting"?

PMID- 16906051
TI  - High-volume "-omics" technologies and the future of molecular epidemiology.

PMID- 16906052
TI  - Cotinine and spontaneous abortion: might variations in metabolism play a role?

PMID- 16906054
TI  - Estimating the burden of disease and the benefits of prevention.

PMID- 16906053
TI  - Triggers of clinical coronary heart disease.

PMID- 16906055
TI  - Changes in systolic blood pressure associated with lead in blood and bone.
AB  - BACKGROUND: Several studies have examined longitudinal associations of blood
      pressure change or hypertension incidence with lead concentration in blood or
      bone. It is not clear whether the observed associations reflect an immediate
      response to lead as a consequence of recent dose or rather are a persistent
      effect of cumulative dose over a lifetime. METHODS: We followed 575 subjects in a
      lead-exposed occupational cohort in South Korea between October 1997 and June
      2001. We used generalized estimating equation models to evaluate blood pressure
      change between study visits in relation to tibia lead concentrations at each
      prior visit and concurrent changes in blood lead. The modeling strategy
      summarized the longitudinal association of blood pressure with cumulative lead
      dose or changes in recent lead dose. RESULTS: On average, participants were 41
      years old at baseline and had worked 8.5 years in lead-exposed jobs. At baseline,
      the average +/- standard deviation for blood lead was 31.4 +/- 14.2 microg/dL,
      and for tibia lead, it was 38.4 +/- 42.9 microg/g bone mineral. Change in
      systolic blood pressure during the study was associated with concurrent blood
      lead change, with an average annual increase of 0.9 (95% confidence interval =
      0.1 to 1.6) mm Hg for every 10-microg/dL increase in blood lead per year.
      CONCLUSION: The findings in this relatively young population of current and
      former lead workers suggest that systolic blood pressure responds to lead dose
      through acute pathways in addition to the effects of cumulative injury.

PMID- 16906056
TI  - Alice Hamilton: pioneer occupational epidemiologist.

PMID- 16906057
TI  - Maternal smoking as a confounder in studies of air pollution and infant
      mortality.

PMID- 16906059
TI  - Paternal age and preterm birth.

PMID- 16906060
TI  - Effect of erroneous surgical procedures on recurrence and survival rates for
      patients with osteosarcoma.
AB  - To determine whether inappropriate surgical procedures based on an initial
      misdiagnosis affected recurrence and survival rates, we retrospectively reviewed
      the surgical treatment and results of 117 patients with high-grade osteosarcomas
      treated from January 1, 1990 to December 31, 2000. Nine patients had
      intralesional curettage performed at other institutions based on an erroneous
      diagnosis of a benign lesion. Two of the nine patients had amputations and seven
      patients had limb-salvage procedures. Of the 108 patients who were not
      misdiagnosed, six patients had amputations and 102 patients had limb-salvage
      procedures. All patients received neoadjuvant therapy. Fifteen of the 117
      patients had local recurrences. Patients who had erroneous surgical procedures
      based on the initial misdiagnosis of osteosarcoma had an increased risk of local
      recurrence and decreased 10-year survival rate. Response to adjuvant therapy and
      the amount of previous violation of natural tumor barriers should be evaluated
      carefully before deciding surgical treatment.

PMID- 16906061
TI  - The natural history of new orthopaedic devices.
AB  - Each year, hundreds of new devices and implants are introduced for orthopaedic
      surgeons. However, the proportion of new devices which ultimately will be
      successful is unknown. We investigated the natural history of new devices
      introduced to the orthopaedic market. From a list of all devices approved for use
      by the Food & Drug Administration 5 and 10 years before, a cohort of 100 devices
      was randomly selected using a random number list. Companies were contacted
      regarding the safety record and current availability of these devices. The
      company response rate was 93%. Forty-seven percent of devices approved 10 years
      ago and 25% of devices approved 5 years ago no longer were on the market. Of the
      55 companies studied, 18 (33%) were out of business and their devices no longer
      were available. Devices approved 10 years ago were more likely to be unavailable
      than devices approved 5 years ago. Devices introduced by smaller companies were
      more likely to be unavailable. The majority of unavailable devices were
      discontinued not for clinical problems, but for poor market performance. Only 2%
      of devices studied had safety problems. Approximately 50% of devices approved for
      introduction to the orthopaedic marketplace no longer are available 10 years
      later. However, major device-related problems seem uncommon.

PMID- 16906062
TI  - Payer type has little effect on operative rate and surgeons' work intensity.
AB  - Does health-care payer type affect the rate of operative treatment and surgeons'
      work intensity for patients with orthopaedic conditions? We analyzed the clinical
      and financial data collected during 6 consecutive years (1999-2004) for a group
      practice of 40 orthopaedic surgeons. We examined the rate of operative treatment
      and surgeons' work intensity (total physician's work Resource-based Relative
      Value System units) by diagnosis, patient age, and payer type. The eight payer
      types were: capitation health maintenance organization, health maintenance
      organization, preferred provider organization, indemnity, self-pay, Workers'
      Compensation, Medicaid, and Medicare. There were 230,306 patients with 526 unique
      primary diagnoses. Diagnosis accounted for most of the variability in operative
      rates and surgeons' work intensity. After adjusting for differences attributable
      to diagnosis, payer type had little effect on the rate of operative treatment and
      surgeons' work intensity.

PMID- 16906063
TI  - Peroneal nerve branching suggests compression palsy in the deformities of Charcot
      Marie Tooth disease.
AB  - Altered expression of the PMP-22 protein may be implicated in Charcot-Marie-Tooth
      disease and the much rarer disease, hereditary liability to pressure palsy. An
      element of chronic pressure palsy may explain the unique distribution of motor
      imbalance in patients with Charcot-Marie-Tooth disease. If this is the case,
      innervation of the lateral leg motor units should show sufficient anatomic
      segregation to explain the variable disease patterns. Twelve fresh cadaver
      specimens were dissected to examine the innervation of the anterior and lateral
      compartment muscles from the peroneal nerve. Nine specimens had a branch to the
      peroneus longus at or proximal to nerve passage of the posterior fibular neck.
      The first branch to the peroneus longus was 2.1 +/- 6.7 mm proximal, and the
      first branch to the peroneus brevis was 110.9 +/- 19 mm distal. The nerve to the
      tibialis anterior originated within 5 mm of the reference point and wrapped
      transversely along the fibular neck for 17.2 +/- 1.4 mm. These discrete pathways
      to the individual motor units in the anterolateral leg were consistent with the
      possible implication of chronic pressure palsy in the patterns of atrophy in
      Charcot-Marie-Tooth disease.

PMID- 16906064
TI  - Aseptic loosening is uncommon with uncemented proximal tibia tumor prostheses.
AB  - Aseptic loosening is a frequent cause of failure of cemented proximal tibia tumor
      endoprostheses. Uncemented prostheses may lessen this risk. We identified
      complications including aseptic loosening that affected prosthetic survival, limb
      survival and functional outcome for 44 consecutive patients after sarcoma
      resection from the proximal tibia and uncemented endoprosthetic reconstruction.
      At a mean final followup of 60 months (range, 9-152 months), there were no cases
      of aseptic loosening. Twelve (27%) patients suffered 14 complications leading to
      prosthetic failure due to infection (n = 7), stem fracture (n = 2), rotational
      instability (n = 1), vascular compromise (n = 2) and local tumor relapse (n = 2).
      However, limb salvage was successful in 37 of 44 (84%) patients. Functional
      assessment for 35 patients revealed a mean Toronto Extremity Salvage Score of
      77/100 (range, 33-98) and Musculoskeletal Tumor Society 1987 and 1993 scores of
      25/35 (range, 13-31) and 75/100 (range, 33-97), respectively. Mean knee joint
      flexion was 91 degrees (range, 0-110 degrees ) and knee extension lag was 6
      degrees (range, 0-30 degrees ). Three patients with knee extensor complications
      had inferior functional outcomes. Aseptic loosening is uncommon with uncemented
      proximal tibia reconstruction, but decreasing other complications at this
      location remains challenging. LEVEL OF EVIDENCE: Therapeutic study, level IV-1
      (case series).

PMID- 16906065
TI  - Pedographic, clinical, and functional outcome after scarf osteotomy.
AB  - The aim of this study was to investigate whether a Scarf osteotomy for hallux
      valgus correction achieves a good functional restoration with pain reduction,
      improved mobility, and hallux loading. Therefore, we prospectively studied 32
      patients who had a Scarf osteotomy for unilateral hallux valgus. We performed
      clinical, radiographic, and pedographic evaluations after a mean followup of 33
      months to assess clinical and functional outcomes. The mean postoperative
      American Orthopaedic Foot and Ankle Society score was 89 points. The hallux
      valgus angle improved from 32.5 degrees to 6.2 degrees , and the intermetatarsal
      angle improved from 15.5 degrees to 6.6 degrees . The postoperative pedographic
      patterns showed that the maximum force and impulse decreased under the lateral
      forefoot and increased under the medial forefoot and hallux. The first ray became
      more important in the roll-over process. There was a moderate relationship
      between satisfaction and postoperative hallux valgus angle. The Scarf osteotomy
      improved the pain situation, the walking capacity, and led to an improved
      contribution of the hallux in the roll-over process. Therefore, this surgical
      procedure restores forefoot function and normalizes plantar pressure patterns.

PMID- 16906066
TI  - Abdominal pain in a 71-year-old woman.

PMID- 16906068
TI  - Cemented rotating hinge endoprosthesis for limb salvage of distal femur tumors.
AB  - We retrospectively ascertained the outcomes and complications with a cemented
      rotating hinge implant. Implant failure was defined as amputation of the affected
      limb and revision of part or all of the components. We included 77 consecutive
      distal femoral replacements performed between 1989 and 2004. The mean age was 42
      years (range, 12-87 years) and the mean length of followup was 52 months (range,
      1.5-157 months). Five-year implant survival was 84% and 10-year survival was 79%.
      There were 67 bone sarcomas, two soft tissue sarcomas and eight metastatic
      carcinomas. At followup, 54 patients had no evidence of disease, 16 were alive
      with disease, and seven were dead from disease. Six patients had deep infection,
      two of which required amputations. There were five local recurrences; three
      needed amputation and two soft-tissue excisions only. Three patients sustained a
      tibial bearing fracture and one required replacement of loose bumper. No revision
      was performed for stem loosening, stem fracture, or bushing wear. Musculoskeletal
      Tumor Society 1987 scores averaged 30 and Toronto Extremity Salvage Scores
      averaged 77.6 at latest followup. Cemented endoprosthesis is a reliable procedure
      after resection of the distal femur for tumors. LEVEL OF EVIDENCE: Therapeutic
      study, level IV (case series).

PMID- 16906067
TI  - Hip pain in a 21-year-old man.

PMID- 16906069
TI  - Adherence of Staphylococcus epidermidis to biomaterials is augmented by PIA.
AB  - Staphylococcus epidermidis is the most common cause of orthopaedic prosthetic
      device infections. Polysaccharide intercellular adhesin (PIA) is important in the
      pathogenesis of intravascular catheter-associated infection, and has an essential
      role in cellular aggregation and biofilm formation. However, the role of PIA in
      orthopaedic infections is less well understood. We used genetically defined
      strains of S. epidermidis in an in vitro adherence assay to assess the importance
      of PIA in the adherence to various orthopaedic biomaterials. On all biomaterials
      tested (zirconia, ultra-high molecular weight polyethylene,
      polymethylmethacrylate, cobalt chromium, titanium, stainless steel, and
      silastic), PIA-positive S. epidermidis 1457 exhibited greater levels of adherence
      thanS. epidermidis 1457 M10, an isogenic icaA Tn917 mutant. PIA appears to play a
      critical role in the adherence of S. epidermidis to orthopaedic biomaterials, and
      may serve as an important virulence determinant in orthopaedic prosthetic device
      infections.

PMID- 16906070
TI  - Local antibiotic delivery with OsteoSet, DBX, and Collagraft.
AB  - Biodegradable local antibiotic delivery systems have gained interest for
      prophylaxis and treatment of musculoskeletal infections. We studied the
      biodegradable materials Osteo- Set, DBX and Collagraft for local delivery of
      vancomycin and gentamicin in vitro. We determined the antimicrobial activity of
      vancomycin and gentamicin after mixing with each biodegradable material and
      determined the release of each antimicrobial from each material in an
      intermittent flow chamber. Antimicrobial activity was expressed as percent of
      antimicrobial loaded into each sample that was detected; antimicrobial release
      was expressed as concentration (microg/mL) after timed intervals of chamber flow,
      peak concentration, area under the curve and percent antimicrobial recovered.
      Activity of vancomycin after mixing with Osteo- Set, DBX and Collagraft was >
      73%. Activity of gentamicin after mixing with DBX was 100%; after mixing with
      OsteoSet and Collagraft it was reduced to < 61%. AUC0-48hrs of vancomycin was
      469, 426 and 432 microg x hr/mL, and the AUC0-48hrs of gentamicin was 368, 306
      and 301 microg x hr/mL after release from OsteoSet, DBX, and Collagraft,
      respectively. Recovered percentages of vancomycin were 39%, 11% and 25%, and
      recovered percentages of gentamicin were 39%, 9% and 23% after release from
      OsteoSet, DBX, and Collagraft, respectively. OsteoSet, DBX and Collagraft may be
      suitable for local delivery of vancomycin and gentamicin.

PMID- 16906071
TI  - Septic arthritis of the shoulder, elbow, and wrist.
AB  - Septic arthritis of the shoulder, elbow, or wrist is not commonly described in
      the literature. We evaluated the micro- biology of these infections and the
      diagnostic role of joint aspirate findings. This retrospective study includes 52
      patients, diagnosed from 1994 to 2004, with septic arthritis of the shoulder (n =
      17), elbow (n = 23), or wrist (n = 12). The mean age was 44.3 years, and 54% of
      patients (28/52) had comorbidities. The prevalence of Staphylococcus aureus was
      76%. Ninety-six percent of aspirates with positive cultures had a
      polymorphonuclear differential count greater than 85% of the total aspirate white
      blood cell count. Staphylococcus aureus is the most prevalent organism. A high
      index of suspicion for septic arthritis is necessary for all patients with upper
      extremity joint complaints, irrespective of age and medical status. The joint
      aspirate differential white blood cell count may be helpful in the diagnosis.

PMID- 16906072
TI  - Unusual aerobic and anaerobic bacteria associated with prosthetic joint
      infections.
AB  - The association of certain microorganisms, such as Staphylococcus epidermidis,
      Staphylococcus aureus, and beta-hemolytic streptococci, with prosthetic joint
      infection (PJI) has been recognized for many years. To our knowledge, a
      systematic review of the presentation and management of less commonly encountered
      species of coagulase-negative staphylococci, nutritional-variant streptococci,
      aerobic non-spore and spore forming Gram-positive or anaerobic bacteria is not
      available. We therefore sought to provide a comprehensive literature review of
      PJI due to these microorganisms that will provide a valuable and quick reference
      for clinicians caring for these patients. We conducted a Medline search of all
      case reports and case series of PJI due to unusual aerobic and anaerobic
      bacteria. The presentation, surgical, and medical management strategies were
      reviewed. Appropriate medical and surgical management of such infections is
      complex and evolving as newer diagnostic tests, surgical techniques and
      antimicrobials become available. Management of patients with these infections
      requires close collaboration between the orthopaedic surgeon, infectious disease
      specialist and microbiology laboratory.

PMID- 16906073
TI  - Septic arthritis in patients with human immunodeficiency virus.
AB  - The literature contains few descriptions of the infective organisms and
      diagnostic issues associated with musculoskeletal infections in patients with
      HIV. We retrospectively reviewed 19 patients with HIV treated at our
      musculoskeletal infection ward for septic arthritis. The mean CD4 count was
      154/mm (range, 7-482/mm), and 11 patients had a CD4 count < 200/mm and were
      diagnosed with AIDS. The most common pathogen (six patients) was oxacillin
      resistant Staphylococcus aureus. Mycobacterial infections occurred in three
      patients but no fungal pathogens were identified. Septic arthritis was
      monoarticular in 14 patients and involved the knee in eight patients, the hip in
      three patients, and the wrist in three patients. Five patients presented with
      polyarticular septic arthritis. All mycobacterial infections and four of the five
      polyarticular infections occurred in patients with a CD4 count < 200/mm. Patients
      with CD4 count < 200/mm had a lower joint fluid WBC count compared to patients
      with a CD4 count > 200/mm (40,500 vs 69,000/mm). Oxacillin-resistant
      Staphylococcus aureus was the most common pathogen. A high index of suspicion for
      Mycobacterium. tuberculosis arthritis and polyarticular septic arthritis is
      necessary in patients with HIV and a CD4 count < 200/mm.

PMID- 16906074
TI  - Function correlates with deltoid preservation in patients having scapular
      replacement.
AB  - Advocates of scapular replacement suggest sparing the deltoid should be a
      prerequisite for use of a scapular prosthesis. We evaluated the importance of a
      functioning deltoid in scapular replacement for malignant tumors. We
      retrospectively reviewed 19 patients who received scapular prostheses after
      resection of a malignant tumor. The median followup was 18 months (range, 12-124
      months). The axillary nerve was resected in eight patients and spared in 11
      patients. The average International Society of Limb Salvage score was 25 of 30
      points (range, 21-27 points). The average scores for patients with and without
      axillary nerve resection were 24 points (range, 21-25 points) and 26 points
      (range, 23-27 points), respectively. There was a difference between the two
      groups in hand positioning, overall function, and pain. However, there were no
      differences in emotional acceptance, lifting ability, or hand dexterity. We favor
      using a scapular prosthesis if there is a functioning deltoid; however resection
      of the deltoid should not be considered an absolute contraindication for scapular
      replacement.

PMID- 16906075
TI  - Clinical utility of percutaneous biopsies of musculoskeletal tumors.
AB  - Percutaneous biopsies are frequently used for musculoskeletal lesions. We suspect
      published accuracy rates (80-97%) overestimate clinical utility. We
      retrospectively reviewed 120 consecutive percutaneous biopsies performed by
      interventional radiologists at our institution. Patients underwent core biopsy,
      fine-needle aspiration (FNA), or both. The biopsy interpretations were considered
      clinically useful if they allowed proper treatment to proceed and not useful if
      they were nondiagnostic or if surgical specimens disagreed with percutaneous
      specimen. Patients were categorized by biopsy type, tissue type, and tumor type.
      Ninety of 120 percutaneous biopsies were clinically useful, 27 were
      nondiagnostic, and three were incorrect; in these latter 30 patients we proceeded
      to open biopsy. Patients with both biopsies had clinically useful results (80.6%)
      more often than FNA or core alone(68.0% and 66.7%, respectively). Biopsies of
      bone lesions were clinically useful more often than those of soft tissue. Myxoid
      histology was associated with decreased clinical accuracy. Clinical utility was
      independent of tumor type. No single characteristic predicted increased
      probability of open biopsy. The clinical utility rate was acceptable, but below
      published accuracy rates. The combination of both biopsies was better than FNA
      alone. Myxoid findings rarely helped to guide definitive treatment. Treatment
      decision making requires balancing biopsy results with clinical data. LEVEL OF
      EVIDENCE: Diagnostic study, level IV.

PMID- 16906076
TI  - Multifocality and multifocal postradiation sarcomas.
AB  - Hypothetically, any site in a radiation portal has potential for late malignant
      transformation. Secondary malignant neoplasms may occur after almost any index
      cancer has been treated with radiation and/or chemotherapy. The incidence of
      secondary malignant neoplasms, histopathology, time delay, radiation dose,
      cytotoxic agents, age and type of initial malignancy, and outcome all negatively
      impact cancer survivors. We highlight the new concept of multifocality, defined
      as greater than two noncontiguous second malignant neoplasms that develop in a
      prior radiation port. We identified 48 patients with postradiation sarcomas from
      three prospectively collected databases. Fifteen of these patients (31%) had
      evidence of multifocal postradiation sarcomas. Five of 10 women had multifocal
      postradiation sarcomas after breast-conserving surgery for carcinoma. The longer
      the time interval between the index cancer and post-radiation sarcoma, the
      greater the likelihood of multifocal malignant transformation occurring. LEVEL OF
      EVIDENCE: Therapeutic study, level III.

PMID- 16906077
TI  - Recalcitrant septic knee arthritis due to adjacent osteomyelitis in adults.
AB  - We asked whether adjacent osteomyelitis with acute septic knee arthritis
      explained a lack of response to initial management, and whether patient
      comorbidities predisposed to the nonresponsiveness. From 147 adult patients (151
      knees) with septic arthritis, we identified 29 patients (33 knees) who had
      persistence or recurrence of symptoms after surgical drainage. Adjacent
      osteomyelitis was present in 31 (94%) of the 33 knees (27 of 29 patients) with
      poor response to treatment. Patients with adjacent osteomyelitis had more
      comorbid conditions (23 of 27 patients, 85%) than patients without osteomyelitis
      (64 of 120, 53%). The most common comorbid conditions in patients with adjacent
      osteomyelitis were diabetes mellitus (10 patients, 37%) and intravenous drug use
      (eight patients, 30%). We identified Staphylococcus aureus in 19 of 31 knees
      (61%) with osteomyelitis, eight (26% of total cases) of which were methicillin
      resistant. Persistence of clinical signs of infection after surgical management
      of septic knee arthritis in adults should raise the suspicion of adjacent
      osteomyelitis, especially in patients with comorbid conditions. Additional
      imaging studies may be necessary to evaluate the distal femur and proximal tibia.

PMID- 16906078
TI  - Fungi, mycobacteria, zoonotic and other organisms in prosthetic joint infection.
AB  - A systematic review of the presentation and management of prosthetic joint
      infection (PJI) due to zoonotic microorganisms, fungi, mycobacteria and other
      unusual microorganisms is not available. We therefore sought to provide a
      resource for the practicing orthopaedic surgeon which will serve as a guide for
      making appropriate decisions in managing such rare, but potentially problematic
      conditions. We conducted a Medline search of all case reports of PJI due to these
      unusual microorganisms. Our review of the current literature showed the diagnosis
      of PJI due to zoonotic microorganisms, fungi, mycobacteria and other unusual
      microorganisms typically necessitates specialized diagnostic tests. Maintaining a
      high index of suspicion in diagnosis of such unusual microorganisms and
      requesting the appropriate laboratory tests at the time of surgical debridement
      is crucial for determining the microbiologic etiology of these infections. The
      appropriate medical and surgical management of such infections is complex and
      often requires the use of special antimicrobials with which the orthopaedist may
      not be familiar. Collaboration with an infectious disease specialist is advisable
      when treating these infections.

PMID- 16906079
TI  - Xylitol and glycine fillers increase permeability of PMMA to enhance elution of
      daptomycin.
AB  - The elution of antibiotics from hand mixed antibiotic-laden
      polymethylmethacrylate (PMMA) must be increased to achieve clinical performance
      equivalent to commercially manufactured antibiotic beads (not available in the
      USA) in the management of musculoskeletal infections. Adding fillers such as
      glycine and dextran to polymethylmethacrylate increases the elution of
      antibiotics from antibiotic-laden PMMA. We propose xylitol, a naturally occurring
      sweetener with direct antibiofilm properties, as a filler material. To compare
      the efficacy of xylitol and glycine as fillers on the elution of antibiotics from
      PMMA, elution studies were performed on mixtures of Palacos
      polymethylmethacrylate and daptomycin (1 gm) with xylitol or glycine as the
      filler (28 g). Xylitol and glycine enhanced the daptomycin activity eluted from
      the polymethylmethacrylate. Xylitol was more effective than glycine, having a
      greater increase in daptomycin release at all data points; on day one xylitol
      increased the elution of daptomycin 2.67 times whereas glycine increased it 1.78
      times also on day one. The eluant concentration of daptomycin remained higher
      longer for xylitol; 3.90 microg/mL for xylitol versus 2.25 microg/mL for glycine
      on day 9. Xylitol is inexpensive and readily available. It can be hand mixed with
      PMMA, and is more effective than glycine as a filler to enhance daptomycin
      release. Considering possible antibiofilm activity, xylitol may be a more
      advantageous choice.

PMID- 16906080
TI  - VEGF and BMP expression in mouse osteosarcoma cells.
AB  - Osteosarcoma is the most common primary bone malignancy. Despite improvements in
      therapy, approximately 30% of patients experience pulmonary metastasis.
      Expression of several growth factors, including VEGF and BMPs, has been
      implicated in tumor progression and metastatic potential. We hypothesized
      increased metastatic potential of mouse osteosarcoma cells positively correlates
      with the expression of VEGF and BMPs. We studied the expression patterns of these
      growth factors in two murine osteosarcoma cell lines with varying degrees of
      metastatic potential: K7M2 (highly metastatic) and K12 (minimally metastatic).
      Expression of VEGF and BMP2 were higher in the metastatic K7M2 cell line. We also
      investigated the effects of the BMP antagonist noggin on osteosarcoma growth
      characteristics in vitro. We noted decreased motility, altered morphology, and
      increased cell death in the highly metastatic K7M2 cell line. Less metastatic K12
      cells showed substantial cell death without clear alteration of motility or
      morphology. These data suggest BMP2 expression may be an important factor in
      osteosarcoma metastasis and noggin administration theoretically could block its
      actions. Inhibition of BMPs and VEGF should be investigated further as a possible
      strategy for decreasing the incidence of pulmonary metastases in osteosarcoma.

PMID- 16906081
TI  - Results of multiple drilling compared with those of conventional methods of core
      decompression.
AB  - We performed multiple drilling as a femoral head-preserving procedure for
      osteonecrosis of the femoral head thinking the therapeutic effects of core
      decompression could be achieved by this simpler procedure than core
      decompression. We retrospectively reviewed 136 patients (163 hips) who had
      multiple drilling using 9/64-inch Steinmann pins for treatment of nontraumatic
      osteonecrosis of the femoral head. The mean followup for patients who did not
      require additional surgery (113 hips) was 87 months (range, 60-134 months). We
      defined failure as the need for additional surgery or a Harris hip score less
      than 75. After a minimum 5-year followup, 79% (31/39) of patients with Stage I
      disease and 77% (62/81) of patients with Stage II disease had no additional
      surgery. All (15/15) small lesions (<25% involvement) and 84% (37/44) of medium
      sized lesions (25-50% involvement) were considered successful. Survival rates of
      patients with Ficat Stages I or II lesions were greater than survival rates for
      patients with Stage III lesions. Hips with a large necrotic area had poor
      results. We had one instance of subtrochanteric fracture through drill entry
      holes. Multiple drilling is straightforward with few complications and produces
      results comparable to results of other core decompression techniques.

PMID- 16906082
TI  - High doses of OP-1 inhibit fibrous tissue ingrowth in impaction grafting.
AB  - A major concern in using growth factors in impaction grafting is the potential
      stimulation of the osteoclastic lineage. A solution would be using an
      osteoconductive material resistant to resorption and providing initial stability
      after reconstruction. Growth factors may promote bone formation in combination
      with such graft materials. We determined whether OP-1 would promote the
      incorporation of impacted morselized allografts and tricalcium
      phosphate/hydroxyapatite (TCP/HA) into host bone, whether bone formation would be
      preceded by an initial process of accelerated resorption, and whether the
      response to OP-1 remodeling/incorporation would be dose-related. We performed two
      bone chamber studies in goats to ascertain the early effects of OP-1 dose on
      resorption and incorporation of impacted morselized allografts and TCP/HA. After
      4 weeks, the incorporation process of impacted morselized allografts and TCP/HA
      was not promoted by OP-1. We observed no signs of accelerated resorption
      preceding bone formation. An increase in OP-1 dose resulted in an inhibition of
      fibrous tissue formation but OP-1 did not promote bone formation. Early failures
      in impaction grafting, using mixes with OP-1, might be explained by the lack of
      fibrous tissue ingrowth and not by increased resorption and remodeling.

PMID- 16906083
TI  - Intraoperative contamination influences wound discharge and periprosthetic
      infection.
AB  - Intraoperative bacterial contamination increases risk for postoperative wound
      healing problems and periprosthetic infection, but to what extent remains
      unclear. We asked whether bacterial contamination of the instruments and bone
      during primary prosthesis insertion was associated with prolonged wound discharge
      and subsequent periprosthetic infection. During 100 total hip arthroplasties,
      four intraoperative cultures were taken from the instruments and two portions of
      removed bone. Postoperatively, the duration of wound discharge was monitored,
      with Day 5 as the cut-off point. All patients were followed for 2 years to
      determine whether periprosthetic infection occurred. Bacterial contamination
      occurred in 36 operative procedures (36%). We found an association between
      intraoperative contamination and prolonged wound discharge, with a relative risk
      of 2.5. The culturing of removed bone had a positive predictive value of 81% to
      90%. Other factors associated with prolonged wound discharge were rheumatoid
      arthritis (relative risk, 6.4), use of cement (relative risk, 1.6), and increased
      blood loss (relative risk, 1.5).

PMID- 16906084
TI  - Brachial plexus lesions after backpack carriage in young adults.
AB  - Carrying a heavy backpack exerts compression on shoulders, with the potential to
      cause brachial plexopathy. We evaluated the incidence and predisposing factors of
      compression plexopathy of the shoulder region in 152,095 military conscripts,
      hypothesizing that a low body mass index and poor physical fitness predispose to
      the plexus lesion. Reports of conscripts with neural lesions of the upper arm
      associated with load carriage were reviewed retrospectively for details
      associated with the condition onset, symptoms, signs, nerve conduction studies,
      and electromyographic examinations. Height, weight, and physical fitness scores
      were obtained from their military training data. The incidence of neural
      compression after shoulder load carriage in Finnish soldiers was 53.7 (95%
      confidence interval, 39.5-67.8) per 100,000 conscripts per year. The long
      thoracic nerve was affected in 19, the axillary nerve in 13, the suprascapular
      nerve in seven, and the musculocutaneous nerve in six patients. Four patients
      (7%) had hereditary neuropathy with susceptibility to pressure palsies (HNPP).
      Symptoms were induced by lighter loads in patients with HNPP. Vulnerability to
      brachial plexopathy was not predictable from body structure or physical fitness
      level. To prevent these lesions, awareness of the condition and its symptoms
      should be increased and backpack designs should be improved.

PMID- 16906085
TI  - Incidence of lateral release in total knee arthroplasty in standard and mini
      incision approaches.
AB  - Minimally invasive total knee arthroplasty is a relatively new technique. There
      are limited clinical data on outcomes in patients having this procedure. We
      report the incidence of lateral release of the patella during total knee
      arthroplasty performed by one surgeon in 106 consecutive knees. The rate of
      release is compared between knees that received a mini incision with a limited
      medial parapatellar arthrotomy and those that received a standard approach. Our
      data suggest there is no correlation between size of incision and incidence of
      lateral release of the patella.

PMID- 16906086
TI  - Abductor length alterations in hips with SCFE deformity.
AB  - Proximal femoral osteotomy may improve clinical outcomes in patients with
      residual deformity after slipped capital femoral epiphysis. Whether this
      procedure improves abductor mechanics is not well established. We hypothesized
      that abductor lengths would be shorter in patients with slipped capital femoral
      epiphysis compared with normal controls, and a femoral neck base osteotomy would
      create more normal abductor lengths than an osteotomy performed below the greater
      trochanter. Abductor muscle lengths were measured in normal, mild, and severe
      slipped capital femoral epiphyses sawbone models and after two methods of
      surgical correction. We observed decreases in abductor lengths in patients with
      slipped capital femoral epiphysis compared with normal controls when positioned
      in greater than 45 degrees flexion. There were fewer differences in abductor
      lengths after femoral neck base osteotomies than after subtrochanteric
      osteotomies. The femoral neck base osteotomy approximated normal abductor lengths
      more closely than the subtrochanteric osteotomy. The femoral neck base osteotomy
      restored the hip abductor relationship better than an osteotomy performed below
      the greater trochanter. We did not address the question of whether this improved
      relationship directly influenced function.

PMID- 16906087
TI  - Mechanical effects of partial sacrectomy: when is reconstruction necessary?
AB  - We examined the mechanical consequences of high partial transverse sacrectomy.
      Ten human cadaveric pelves were randomly assigned to three groups. In the Control
      Group, the sacrum was left entirely intact. In Group I, transverse partial
      sacrectomy was performed just caudal to the S1 neural foramina. In Group II,
      transverse partial sacrectomy was performed just cephalad to the S1 neural
      foramina. Each pelvis was mounted on a testing apparatus and loaded vertically at
      the L4/L5 disk space until failure occurred. The average resection of the
      sacroiliac joints was 16% in Group I, and 25% in Group II. The average load to
      failure was 3014 N in the Control Group, 2166 N in Group I, and 1045 N in Group
      II. The average stiffness was 353 N/mm in the Control Group, 222 N/mm in Group I,
      and 100 N/mm in Group II. All specimens failed because of fractures through the
      sacrum (mostly Denis Zone II) in the sagittal plane. Using the literature to
      predict normal forces at the lumbosacral junction, we suggest Group I pelves
      could withstand postoperative mobilization without fracture, whereas Group II
      would probably not. Reconstruction should therefore be considered when performing
      transverse partial sacrectomy above the S1 nerve root.

PMID- 16906088
TI  - Proteomic profiling in musculoskeletal oncology by MALDI mass spectrometry.
AB  - Proteomics is the emerging technology that evaluates normal and abnormal protein
      expression in tissues. Tissue profiling by matrix assisted laser desorption
      ionization mass spectrometry (MALDI MS) is a proteomic tool that permits the
      rapid detection of proteins expressed in tissues and serum. To date, tissue
      profiling has been successfully utilized to detect proteins specific to various
      cancers, including those of non-small cell lung carcinoma and glioblastoma
      multiforme. The usefulness of histological analyses to predict soft tissue
      sarcoma (STS) behavior has plateaued, and a critical need exists to identify
      other means to objectively predict tumor grade and behavior. We describe tissue
      profiling as a tool for orthopaedic research, and review recent work utilizing
      the technology for detecting proteins that differentiate low grade from high
      grade STS. We used MALDI MS tissue profiling technology to detect differentially
      expressed proteins in high grade and low grade STS. LEVEL OF EVIDENCE: Level I,
      prognostic study.

PMID- 16906089
TI  - Toxic effects of gentamicin on marrow-derived human mesenchymal stem cells.
AB  - We hypothesized that the high concentrations of gentamicin achieved after local
      administration would have toxic effects on human mesenchymal stem cells. These
      cells were isolated from bone marrow from three healthy adult donors and cultured
      with different concentrations of gentamicin (0 microg/mL, 50 microg/mL, 100
      microg/mL, and 200 microg/mL) for 7 days. After 7 days of gentamicin exposure, we
      examined cell viability, proliferation, and in vitro and in vivo
      osteochondrogenic capacity. Gentamicin did not have an adverse effect on the
      viability of human mesenchymal stem cells in all test groups, but did inhibit
      cell proliferation at concentrations of 100 microg/mL and 200 microg/mL. In in
      vitro osteogenesis, gentamicin decreased the DNA content and alkaline phosphatase
      activity of human mesenchymal stem cells at an early stage (Days 4 and 8) in a
      dose-dependent manner. For chondrogenesis, glycosaminoglycan content and Type II
      and Type X collagen deposition were lower in the pellets made with cells expanded
      in gentamicin at 100 or 200 microg/mL relative to cells expanded in medium
      without gentamicin. A comparable effect on osteochondrogenesis was observed in an
      in vivo model. At a high concentration, gentamicin inhibits proliferation and
      differentiation of human bone marrow mesenchymal stem cells and could compromise
      the bone-healing process.

PMID- 16906090
TI  - How do serum cobalt and chromium levels change after metal-on-metal hip
      resurfacing?

PMID- 16906091
TI  - Diffuse pigmented villonodular synovitis: preliminary results with intralesional
      resection and p32 synoviorthesis.
AB  - Because of the high local recurrence rate associated with surgical resection
      alone, patients with diffuse intraarticular pigmented villonodular synovitis were
      treated with surgical resection followed by colloidal chromic P32 synoviorthesis.
      The medical records of nine consecutive patients treated in this manner were
      reviewed retrospectively to determine the recurrence rate of pigmented
      villonodular synovitis. All patients had either one or two surgical resections
      (arthroscopy in one patient, open resection in seven, arthroscopy and open
      resection in one). The involved joints included six knees and one each, ankle,
      elbow, and hip. Eight of the nine patients remained recurrence free at a mean
      followup of 38 months (range, 19-60 months) after surgery. One patient had a
      suspected asymptomatic recurrence documented by magnetic resonance imaging 29
      months after surgery. Seven patients reported their normal activities as
      unrestricted. Five reported improved activity levels, one reported the activity
      level remained the same, and one reported activity as the same or better. None
      reported reduced activity levels. In these patients synoviorthesis with colloidal
      chromic P32 following gross resection of all obvious pigmented villonodular
      synovitis provided local disease control in all but one.

PMID- 16906092
TI  - Periosteal osteosarcoma: long-term outcome and risk of late recurrence.
AB  - The long-term outcome of periosteal osteosarcoma is not well defined. We sought
      to examine the disease-specific survival and risk of late recurrence or
      dedifferentiation in a cohort of 29 patients with average of 15.8 years followup.
      Disease-free survival was 83%, with five patients dying of disease at an average
      of 26 months after presentation. Survival was similar with respect to anatomic
      location, pathologic grade, and limb-salvage resection. All instances of local
      recurrence, metastatic disease, and death occurred within 3 years after
      presentation. There were no instances of dedifferentiation. Long-term disease
      free survival is possible after resection of the local recurrence. Limb-salvage
      therapy seems to offer survival equivalent to amputation, and there does not seem
      to be a substantial risk of late recurrence, dedifferentiation, or disease
      progression.

PMID- 16906094
TI  - Survival of tumor megaprostheses replacements about the knee.
AB  - Limb salvage surgery is an effective procedure with a low risk of tumor
      recurrence. In an attempt to define the incidence of implant failure at 2, 5, and
      10 years postoperatively, we retrospectively reviewed implant survival in a group
      (n = 105) of pediatric (< 18 years of age) and adult patients who were treated
      with distal femoral and/or proximal tibial implants for extremity tumors. Issues
      regarding the timing of failure, reason for failure, and whether pediatric
      patients had higher rates of failure were posed as secondary questions. The
      median followup was 57 months (1-235 months). Thirty-two (32/105, 31%) patients
      had 42 implant failures. The mean prosthesis Kaplan-Meier survivorship of the
      index group was 84% at 2 years, 73% at 5 years, and 59% at 10 years. Forty-seven
      percent of all failures occurred within 2 years postoperatively, and 69% occurred
      within 5 years postoperatively. Pediatric patients had a higher failure rate than
      adults (42% versus 24%). Aseptic loosening was the most common reason for failure
      (n = 18/32; 56%). The incidence of failure in tumor megaprostheses is similar to
      early published literature and the incidence of these failures is highest within
      the first 3 years. LEVEL OF EVIDENCE: Therapeutic study, level IV.

PMID- 16906095
TI  - The high variability of tibial rotational alignment in total knee arthroplasty.
AB  - Although various techniques are advocated to establish tibial rotational
      alignment during total knee arthroplasty, it is unknown which is most repeatable.
      We evaluated the precision and accuracy of five tibial rotational alignment
      techniques to determine whether computer-assisted navigation systems can reduce
      variability of tibial component rotational alignment when compared to traditional
      instrumentation. Eleven orthopaedic surgeons used four computer-assisted
      techniques that required identification of anatomical landmarks and one that used
      traditional extramedullary instrumentation to establish tibial rotational
      alignment axes on 10 cadaver legs. Two computer-assisted techniques (axes between
      the most medial and lateral border of the tibial plateau, and between the
      posterior cruciate ligament [PCL] and the anterior tibial crest) and the
      traditional technique were least variable, with standard deviations of 9.9
      degrees, 10.8 degrees, and 12.1 degrees, respectively. Computer-assisted
      techniques referencing the tibial tubercle (axes between the PCL and the medial
      border or medial 1/3 of the tubercle) were most variable, with standard
      deviations of 27.4 degrees and 28.1 degrees. The axis between the medial border
      of the tibial tubercle and the PCL was internally rotated compared to the other
      techniques. None of the techniques consistently established tibial rotational
      alignment, and navigation systems that establish rotational alignment by
      identifying anatomic landmarks were not more reliable than traditional
      instrumentation.

PMID- 16906093
TI  - Endoprosthetic reconstruction for neoplasms of the proximal femur.
AB  - Limb salvage has become an important alternative to amputation in the treatment
      of bone neoplasms. We sought to determine whether the survivorship of modular
      proximal femur endoprostheses compares to that of custom implants and if
      specified factors predict failure. We additionally assessed the intermediate
      clinical and functional results with regard to complications and outcome. We
      retrospectively reviewed 96 consecutive patients who underwent endoprosthetic
      reconstruction for neoplastic disease and assessed patient, implant, and limb
      survivorship. The mean patient age was 59 years (range, 14-86 years). The average
      duration of followup was 18.1 months (range, 1-129 months). Nine (9.3%)
      prostheses failed and the rate of revision was 7.3% (7/96). Overall implant
      survival was 82% at 5 years and 10 years. Survivorship of the limb was 99% at 5
      years. Patients in whom the articulating head segment was a total hip had a
      higher rate of revision compared with those who had undergone bipolar
      replacement. The mean MSTS score was 22 points (range, 15-25 points). Modular
      endoprosthetic replacement of the proximal femur is a durable reconstructive
      option and implants will generally outlive the patient with neoplastic disease.
      Bipolar head segments should be used whenever possible because of increased
      survival and decreased rates of dislocation. LEVEL OF EVIDENCE: Therapeutic
      study, level IV (case series).

PMID- 16906096
TI  - Comparison of total knee arthroplasty in stiff and ankylosed knees.
AB  - We compared the results of total knee arthroplasties in patients with stiff or
      ankylosed knees. We retrospectively reviewed 90 total knee arthroplasties in 52
      patients with minimum 2 years followup who had less than a 50 degrees arc of
      flexion preoperatively. Preoperative and intraoperative data were retrieved from
      a computerized database. Patients were followed for an average of 6.5 years at an
      outpatient department. Knee Society knee scores improved from 34.6 points
      preoperatively to 89.5 points postoperatively in the stiff knees and from 47
      points preoperatively to 75 points postoperatively in the ankylosed knees. The
      arc of flexion improved from 35 degrees -69 degrees preoperatively to 1 degrees 
      94 degrees postoperatively in the stiff knees and from 0 degrees to 3 degrees -77
      degrees in the ankylosed knees. There were major complications in four of the 26
      ankylosed knees and in two of the 64 stiff knees. The data suggest results of
      total knee arthroplasty are better in patients with stiff knees than in patients
      with ankylosed knees.

PMID- 16906097
TI  - Prognosis of radiation-induced bone sarcoma is similar to primary osteosarcoma.
AB  - Radiation-induced sarcoma of bone (RISB) is thought to be associated with a poor
      prognosis. The purpose of this study was to determine disease-free and overall
      survival of patients treated for RISB, and whether there is a role for limb
      sparing surgery. Twenty-four patients had a mean latency of 16 years between
      radiation for their index cancer and RISB diagnosis. The most common tumor was
      osteosarcoma (n = 17). Ten patients with localized disease treated aggressively
      with chemotherapy and surgical resection had estimated 5-year disease-free and
      overall survival rates of 58% and 69% respectively. Patients treated by surgery
      alone or those with metastases at diagnosis had inferior outcomes. Patients who
      received a complete course of chemotherapy demonstrated better histologic tumor
      response and improved survival. There was no difference in survival between the
      limb sparing surgery (n = 12) or amputation (n = 8) groups. However, limb salvage
      patients had slightly higher rates of local tumor relapse and post-operative
      complications. Functional outcome following limb sparing surgery for 10 patients
      with RISB was similar to a matched cohort treated for primary osteosarcoma. An
      aggressive treatment approach for patients with RISB may provide similar rates of
      local recurrence and metastasis and functional outcomes compared to patients with
      primary osteosarcoma. LEVEL OF EVIDENCE: Therapeutic study, level IV-1.

PMID- 16906099
TI  - Continuity and function of patellar tendon host-donor suture in tibial allograft.
AB  - Reconstruction of extensor mechanism after proximal tibia tumor resection is a
      major concern, especially in young and physically active patients. We evaluated
      patellar tendon host-donor reattachments in 42 consecutive proximal tibia allo-
      graft reconstructions after bone tumor resection to determine if patellar tendon
      length and integrity was maintained, and if active knee extension and adequate
      function was achieved. Patellar tendon length was radiographically measured in
      all patients by the Insall-Salvati index while magnetic resonance was available
      in 19 patients to evaluate imaging integrity. Eight patients were not available
      for functional assessment, leaving 34 patients for clinical evaluation with the
      Musculoskeletal Tumor Society scoring system. According to the Insall-Salvati
      index evaluation, the reconstructed patellar tendon remained stable with no
      elongation between preoperative and postoperative measurements (1.15 versus
      1.13). Postoperative magnetic resonance images showed a continuous patellar host
      donor tendon in all. Active knee extension was restored in all functionally
      evaluated patients with an average functional score of 26.6 points. Twenty-four
      patients had no extensor lag, while ten had an average residual extensor lag of
      6.5 degrees . Our findings suggest patellar tendon reconstruction with allogeneic
      tissue from the proximal tibia allograft sutured to the recipient's remnant
      patellar tendon can restore and stabilize active knee extension. LEVEL OF
      EVIDENCE: Therapeutic study, level IV (case series).

PMID- 16906098
TI  - Recent intraarticular steroid injection may increase infection rates in primary
      THA.
AB  - We retrospectively determined the rate of therapeutic intraarticular steroid
      injection within 1 year before total hip arthroplasty (THA) for osteoarthritis
      and whether the injection of the steroid increased the risk of infection. In a
      retrospective matched cohort study, 224 primary THAs (217 patients) implanted
      within 1 year of intraarticular steroid injection (Group 1) were compared with
      224 primary THAs (220 patients) in patients who had not received an injection
      (Group 2). The mean time between injection and THA was 112 days (SD, 81 days). In
      Group 1, there were three deep and 11 superficial infections compared with one
      deep and eight superficial infections in Group 2. The hazard ratios of deep and
      superficial infections were 3 (95% CI, 0.3, 29.8) and 1.5 (95% CI, 0.6, 3.6),
      respectively. Intraarticular steroid injection within 1 year of THA did not
      affect postoperative rates of infection. However, the mean time from steroid
      injection to THA was 44 days (SD, 23 days) in the few patients who had deep
      infection develop. While not statistically significant, this raises a concern of
      increased risk of deep infection when receiving a steroid injection within 6
      weeks of THA. Caution should be used before giving an intraarticular steroid
      injection within 2 months before THA.

PMID- 16906100
TI  - Forearm mass in an adolescent.

PMID- 16906101
TI  - An unusual complication of radiofrequency ablation treatment of osteoid osteoma.

PMID- 16906102
TI  - Dendritic cell immunotherapy is effective for lung metastasis from murine
      osteosarcoma.

PMID- 16906103
TI  - Is PET useful in detecting occult nonpulmonary metastases in pediatric bone
      sarcomas?
AB  - Orthopaedic oncologists are increasingly utilizing positron emission tomography
      (PET) technology in the initial workup and staging of sarcomas and for monitoring
      treatment response. We evaluated the use of PET with fluorine-18-fluoro-2-deoxy D
      glucose (FDG) to detect occult nonpulmonary metastases in patients < age 30 newly
      diagnosed with either Ewing's or osteosarcoma, and the impact of this information
      upon therapeutic decision making. We retrospectively reviewed prospectively
      collected data (1994-2004) on 55 patients age < 30 years old over a 10 year span.
      PET detected metastases in 12/55 (22%) of these patients, eight of whom (67%)
      harbored disease outside the lung; however, only 4/55 (7%) were upstaged to Stage
      IV specifically due to findings determined by PET alone. Three of 17 (18%)
      Ewing's sarcoma patients, but only one of 38 (3%) osteosarcoma patients, were
      upstaged by PET alone. The most important alteration in treatment decisions was
      the substitution of irradiation in lieu of surgery for local control in Ewing's
      sarcoma patients. LEVEL OF EVIDENCE: Diagnostic study, level II.

PMID- 16906104
TI  - Outcome of postradiation osteosarcoma does not correlate with chemotherapy
      response.
AB  - Postradiation osteosarcoma is a rare tumor with a historically poor prognosis.
      Recent reports concerning the prognosis of the disease have been conflicting. We
      ascertained the long-term outcome of patients with this disease treated in the
      era of contemporary chemotherapy. Twenty-seven patients diagnosed with
      postradiation osteosarcoma and treated with chemotherapy and surgical resection
      from 1980-2003 were identified. Demographics, anatomic location, stage, chemo-
      therapy, necrosis rate, recurrence and metastatic rates were recorded; Kaplan
      Meier survival rates were estimated. The median age was 54 years (range, 12-86
      years). Nineteen patients were female and eight patients were male. Median
      followup was 39.2 months (range, 0-218 months). Twenty-two patients received
      induction chemotherapy for a mean of four cycles (range, 2-6 cycles). Mean tumor
      necrosis was 63.5%. Seven patients had 90% necrosis; four of these patients died
      of their disease. The mean survival was 23 months, and the 5-year disease free
      survival estimate was 27.2%. Histologic response to chemotherapy did not
      correlate with survival. Patients who had a latency of greater than 10 years
      after radiation had a better prognosis. Unlike conventional osteosarcoma,
      response to chemotherapy (necrosis) did not have prognostic significance. Current
      chemotherapy regimens fail to impact survival in postradiation osteosarcoma.
      LEVEL OF EVIDENCE: Therapeutic study, level IV (retrospective comparative study).

PMID- 16906105
TI  - Plasma cytokines as markers of aseptic prosthesis loosening.
AB  - The proinflammatory cytokines IL-1beta, IL-8, and TNF-alpha play a major role in
      the process of bone resorption during aseptic loosening of large joint
      prostheses. These cytokines secreted locally during bone resorption in aseptic
      loosening may enter peripheral circulation. Increased concentration of IL-1gamma,
      IL-8, and TNF-alpha in peripheral circulation may indicate aseptic loosening. We
      determined whether bone resorption could be verified by cytokine presence in
      plasma. We recruited 50 patients with aseptic prosthesis loosening, 50 with
      stable prostheses, 50 with osteoarthritis, and 50 healthy individuals. Cytokine
      levels were determined in plasma by ELISA tests. Patients with prosthesis
      loosening had higher plasma levels (IL-10, 3.7 +/- 5.5 pg/mL; IL-8, 14.7 +/- 9
      pg/mL; TNF-alpha, 32.7 +/-+/- 32.4 pg/mL) than patients with stable prostheses
      (IL-1beta, 1.5 +/- 2 pg/mL; IL-8, 8.1 +/- 4.7 pg/mL; TNF-alpha, 22.9 +/- 18.7
      pg/mL), patients with osteoarthritis (IL-1beta, 0.7 +/- 1.1 pg/mL; IL-8, 5.8 +/-
      3.8 pg/mL; TNF-alpha, 9.8 +/- 7.7 pg/mL) and healthy individuals (IL-1beta, 0.7
      +/- 1.1 pg/mL; IL-8, 4.2 +/- 1.3 pg/mL; TNF-alpha, 3.9 +/- 3.9 pg/mL). Our data
      suggest elevated plasma levels of proinflammatory cytokines may be useful as
      markers of bone resorption in the laboratory diagnosis of prosthesis loosening.

PMID- 16906106
TI  - Nasu-Hakola disease (PLOSL): report of five cases and review of the literature.
AB  - The combination of bilateral lytic lesions in the bones of the lower and upper
      extremities and presenile dementia is characteristic of polycystic lipomembranous
      osteodysplasia with sclerosing leukoencephalopathy, also known as Nasu-Hakola
      disease. The clinical course of this rare and fatal disorder is characterized by
      pathologic fractures of these often painful lesions, rapid progression of
      dementia, and death in the fifth decade of life. The radiographic changes may be
      confused with cystic angiomatosis, focal metastasizing hemangioendothelioma, or
      Langerhans' cell histiocytosis. We report five patients to illustrate the
      clinical presentation, radiographic images, psychiatric abnormalities, and new
      genetic findings. Three of the patients were siblings. A biopsy is not needed to
      confirm the diagnosis of polycystic lipomembranous osteodysplasia with sclerosing
      leukoencephalopathy because of the unique combination of radiographic and
      neurologic features.

PMID- 16906107
TI  - The Mark Coventry Award: Prevention of readmission for venous thromboembolism
      after total knee arthroplasty.
AB  - Venous thromboembolism is the most common reason for readmission after total knee
      arthroplasty. Prospective contrast venography was conducted from 1984 to 2003 in
      1321 patients undergoing total knee arthroplasty. Patients with deep venous
      thrombosis or pulmonary embolism were treated with warfarin; those with negative
      venograms received no further anticoagulation. From 1984 to 1992, patients not
      completing venography were discharged without warfarin; since 1993 patients
      without venography received warfarin for 6 weeks. Readmission for deep venous
      thrombosis, pulmonary embolism, or bleeding was tracked for 6 months. Venography
      was completed in 810 patients; 343 (42.3%) had deep venous thrombosis.
      Readmission for venous thromboembolism occurred in 0.6% of patients after total
      knee compared with 1.62% after total hip arthroplasty. Following total knee
      arthroplasty, patients discharged on warfarin (target INR 2.0) had a 0.21%
      readmission rate compared with 1.05% for patients with negative venograms
      discharged without further anticoagulation. One patient suffered a fatal
      pulmonary embolism after negative venography and no outpatient prophylaxis.
      Secondary prophylaxis with extended warfarin therapy reduced venous
      thromboembolism-related readmission. Surveillance venograms were a poor predictor
      of ultimate thromboembolism risk and need for extended anticoagulation therapy.
      We therefore recommend extended warfarin prophylaxis for all patients after
      hospital discharge following total knee arthroplasty.

PMID- 16906108
TI  - The unicompartmental knee: design and technical considerations in minimizing
      wear.
AB  - Unicompartmental knee arthroplasty is an alternative to total knee arthroplasty
      for patients with unicompartmental tibiofemoral noninflammatory disease. Careful
      patient selection and newer instrumentation has reduced the progression of
      arthrosis in the other compartment and tibial loosening, leaving polyethylene
      wear as the predominant failure mechanism in more contemporary designs. Increased
      wear increases the debris volume at the bone-implant interface, and wear
      particles will generate osteolysis leading to component loosening and unreplaced
      compartment degeneration. The design-related factors that minimize wear include a
      polyethylene thickness of greater than 6 mm, a limited shelf age, and a design
      allowing large areas of contact mediolaterally and anteroposteriorly. Congruous
      mobile-bearing implants could play a substantial role in reducing wear if they
      are not associated with dislocation and nonreproducible surgical techniques.
      Important technical factors include accurate instrumentation avoiding component
      to-component malposition and edge loading, allowing slight under-correction of
      the pre- operative deformity. The patient-related factors include a weight limit,
      a functional anterior cruciate ligament, and a correctable frontal deformity.
      Continued research including that related to cross-linking and sterilization
      methods is mandatory to improve polyethylene strength. A better understanding of
      kinematics and contact forces may provide long-term survival and patient
      satisfaction after unicompartmental arthroplasty.

PMID- 16906109
TI  - Management of bone loss in revision total knee arthroplasty.
AB  - Bone deficiencies around the knee can present a substantial challenge during
      revision total knee arthroplasty. Bone loss occurs from stress shielding,
      osteolysis, chronic infection, and bone removed during implant extraction.
      Smaller defects have traditionally been treated with cement filling or allograft
      bone chips. Larger defects can be reconstructed with bulk allografts or custom
      prostheses. A hinged prosthesis may be necessary to account for ligamentous
      insufficiency. In addition to traditional methods of managing bone loss, recent
      developments include the use of metaphyseal-filling implants made of highly
      porous metal. These implants can be press-fit into host bone to accommodate large
      metaphyseal defects. Each revision knee surgery provides unique challenges,
      requiring proficiency in multiple techniques of bone loss management.

PMID- 16906110
TI  - Validity of preoperative demand matching as an indicator of activity after TKA.
AB  - We questioned whether our current preoperative demand matching accurately
      predicted patient activity after TKA. From a prospective database we reviewed 511
      patients who had unilateral, primary TKA from 1994 to 1999 and who were
      preoperatively assessed for five patient characteristics: age, weight, expected
      postoperative activity, health status, and bone stock. We assigned each knee to
      one of four demand categories. Knee implant selection was based on the patient's
      demand category. Other preoperative patient characteristics that could be
      associated with postoperative activity were recorded. The reported postoperative
      patient activity after TKA was determined, and was correlated with each patient
      variable and the demand category. Five hundred eleven TKAs were distributed among
      four demand categories: 39 (7.6%) demand I (high); 156 (30.5%) demand II; 294
      (57.5%) demand III; and 22 (4.3%) demand IV (low). Age, gender, expected
      postoperative activity, bone stock, health status, preoperative activity, Knee
      Society Function Score, and the Hospital for Special Surgery Knee Score
      correlated with postoperative patient activity. The demand category was more
      predictive than any individual variable. The data suggest preoperative demand
      matching a valid approach to predict patient reported activity after TKA. Because
      patient activity is correlated with wear, implant selection and resource
      allocation can be targeted to those patients who may benefit from presumed
      improvements in implant technology.

PMID- 16906111
TI  - A 12-28-year followup study of closing wedge high tibial osteotomy.
AB  - Current indications for high tibial osteotomy (HTO) are controversial although
      several risk factors have been associated with HTO survival. We ascertained the
      influence of preoperative variables in a consecutive series of patients who had
      closing wedge HTO at a minimum of 12 year followup (mean 18-year, range 12 to 28
      years). Three hundred one of an initial 372 high tibial osteotomies (313
      patients) were included (81% followup); 71 knees were eliminated because patients
      died (30 knees) or were lost to followup (41 knees). The mean age was 42 years
      (range, 15-76 years), 194 were men and 119 were women. The osteotomy was fixed by
      a Blount staple and an AO half-tube plate with three screws. Forty-three knees
      (14%) in 39 patients were revised for progression of osteoarthritis at an average
      of 102 months. Survival was 85% at 20 years with revision as the endpoint. Knee
      function was considered satisfactory by 77% of patients. At final followup, 1/2
      of the knees showed radiographic signs of medial osteoarthritis. The most
      important risk factors predicting revision were age greater than 50 years and a
      preoperative arthritis Ahlback grade of 3 or more.

PMID- 16906112
TI  - When computer-assisted knee replacement is the best alternative.
AB  - We studied whether computer-assisted surgery could properly align total knee
      arthroplasty when traditional instrumentation was not possible or appropriate. We
      identified 16 patients (18 knees) who we believed could not be treated using
      traditional instrumentation because of posttraumatic femoral deformity, retained
      femoral hardware, a history of osteomyelitis, or severe cardiopulmonary disease.
      Computer-assisted surgery was successfully used in 17 knees; we were unable to
      accurately register the hip in one morbidly obese patient. We judged the overall
      mechanical axis of the limb using computer-assisted surgery acceptable in 16 of
      17 knees. One patient with a major posttraumatic biplane deformity had an overall
      mechanical axis in 4 degrees of varus. Computer-assisted navigation seemed
      helpful in difficult situations where accurate alignment remains crucial, yet
      traditional instrumentation is not applicable.

PMID- 16906113
TI  - Polyethylene sterilization and production affects wear in total hip
      arthroplasties.
AB  - Production and package sterilization techniques for the polyethylene used in
      acetabular components for total hip arthroplasties are known to affect wear. We
      considered three combinations of techniques: sterilization by radiation in inert
      gas with isostatically molded polyethylene, in inert gas and ram-extruded
      polyethylene, and in air with extruded polyethylene. The intent of this study was
      to confirm that molded polyethylene and polyethylene radiated in inert
      environments reduce wear rates in vivo, to determine the combination of methods
      with the least wear, and to determine how much variance in wear is attributable
      to these methods. We reviewed 150 consecutive total hip arthroplasties done in
      133 patients using 28-mm cobalt-chrome femoral heads and polyethylene-lined,
      titanium, ring-locked acetabular components. The least wear occurred in gamma
      inert-molded polyethylene components. The mean volumetric wear rates were 52.12
      mm3/year for gamma inert-molded, 62.32 mm3/year for gamma inert-extruded, and
      66.09 mm3/year for gamma air-extruded polyethylene components. Relative risk
      assessment found gamma air-extruded and gamma inert-extruded polyethylene
      components to wear 16% and 11% more than gamma inert-molded polyethylene
      components, respectively. Gender, body mass index, and age accounted for the
      greatest amount of the explained variance in volumetric wear (57.5%, 21.6%, and
      14.4, respectively), followed by angle of wear (3.4%), and sterilization and
      production technique (3.2%).

PMID- 16906114
TI  - Tumoral mass on a phalangeal bone in a 19-year-old.

PMID- 16906115
TI  - The John Charnley Award: a study of implant failure in metal-on-metal surface
      arthroplasties.

PMID- 16906116
TI  - Classical osteogenesis imperfecta and allegations of nonaccidental injury.
AB  - We report 12 patients with osteogenesis imperfecta initially diagnosed with
      nonaccidental injuries. As a result, formal hearings, care proceedings, and
      criminal proceedings ensued and seven of the children were removed from their
      parents. The features suggestive of osteogenesis imperfecta at the time of the
      initial investigation included a positive family history in six patients, scleral
      discoloration in nine, abnormally large anterior fontanels in four, excessive
      numbers of wormian bones in four, abnormal bone texture in two, and abnormal
      biochemical findings in three. There were discrepancies between the fractures and
      other clinical evidence of inflicted trauma. The seven patients removed from
      their homes eventually were returned. Five patients remained at home. Information
      was available on the subsequent history of the patients for an average of 4.8
      years. Although seven patients have had additional fractures, there have been no
      additional allegations of nonaccidental injury. When investigating children with
      unexplained fractures, it is important to review carefully their clinical
      history, family history, physical examination findings, and radiographic
      findings. Misdiagnosing patients with nonaccidental injuries causes substantial
      harm to the family and particularly to the child.

PMID- 16906117
TI  - Acetabular cysts heal after successful periacetabular osteotomy.
AB  - The presence of subchondral bone cysts reflects degeneration or defects of the
      articular cartilage and elevated local stresses in the subchondral bone. We asked
      whether the presence of acetabular cysts deleteriously influenced the clinical
      and radiographic results of periacetabular osteotomy for treatment of dysplastic
      hips. We retrospectively reviewed 46 hips in 43 patients with cartilage narrowing
      who had periacetabular osteotomies. Of the 46 hips, 21 had acetabular cysts (cyst
      group) and 25 did not (control group). The average followups were 5.8 and 5.4
      years in the cyst and control groups, respectively. We compared the Harris hip
      score and coverage of the femoral head between the two groups. The clinical
      results were similar between the two groups. There were no differences in
      radiographic evaluations between the two groups at the latest followup. In the
      cyst group, complete or partial healing of the cysts was observed in 17 of the 21
      hips. A postoperative increase in the center-edge angle of 20 degrees or greater
      was found in 14 of the 17 hips. The preoperative presence of acetabular cysts did
      not influence the results of periacetabular osteotomy. Adequate rotation of the
      acetabular fragment induced cyst remodeling.

PMID- 16906118
TI  - Porous tantalum patellar augmentation: the importance of residual bone stock.
AB  - Trabecular metal augmentation of bone defects has been associated with favorable
      bone ingrowth. Animal studies also suggest fibrous tissue attachment to
      trabecular metal can be achieved. We treated 16 patients with total knee
      arthroplasty (18 knees) with severe patellar bone loss using trabecular metal
      patellar reconstruction. The patients were divided into two groups based on the
      amount of residual patellar bone stock present at the time of surgery: Group 1
      (six patients, seven knees) with no patellar bone stock and Group 2 (10 patients,
      11 knees) in whom at least 50% of the patellar component surface was covered by
      host bone. All seven patellar components in Group 1 loosened within 1 year. Two
      of these developed necrosis of the extensor mechanism leading to extensor
      mechanism discontinuity. One component in Group 2 became infected and loosened,
      whereas the remaining 10 components remained stable at minimum 12-month followup.
      Our results suggest stable fixation of a trabecular metal patellar component can
      be achieved when residual bone is present for implant fixation, but early
      loosening is likely to occur when soft tissue is used for fixation to the
      implant.

PMID- 16906119
TI  - 21-year results of the uncemented fully textured lord hip prosthesis.
AB  - We report the updated results for a previously evaluated patient cohort who had
      uncemented total hip arthroplasties using the Lord femoral component. The
      original cohort consisted of 114 total hip arthroplasties (110 patients)
      performed from 1979 to 1984. The patients were followed up for an average of 21
      years postoperatively. We describe the radiographic findings of 57 hips. At the
      last followup 11 (9.6%) of the 114 femoral components were revised or removed.
      Excluding infection there was an 83% 21-year survival according to Kaplan-Meier
      analysis. No significant radiographic changes occurred since the last
      publication. The prostheses are very well-fixed with no signs of loosening. Our
      current findings show the durability of the uncemented Lord femoral component
      indicating this prosthesis provides good long-term results.

PMID- 16906120
TI  - Temporary antibiotic cement-covered gamma nail spacer for an infected nonunion of
      the proximal femur.
AB  - We report the case of an infected nonunion of the proximal femoral in an elderly
      patient. There was extensive involvement of the entire proximal femur precluding
      salvage. An impromptu use of a cephalomedullary nail coated with antibiotic-laden
      bone cement is described, followed by reimplantation with a revision-type
      proximal femoral prosthesis. The patient had resection of the proximal femur,
      placement of a temporary functional spacer, and reimplantation after a course of
      antibiotics, with good success. The method we describe is a reasonable
      alternative when standard off-the-shelf systems or other methods of temporary
      spacer creation are not available.

PMID- 16906121
TI  - Case report: the split flexor carpi ulnaris as a local muscle flap.
AB  - The flexor carpi ulnaris is a useful local muscle flap in the forearm and elbow.
      It is, however, an important palmar flexor and ulnar deviator of the wrist, and
      functional loss may arise from the use of this muscle in its entirety. The flexor
      carpi ulnaris is made up of two distinct neuromuscular compartments. This
      arrangement allows for splitting of the muscle and the potential use of the
      larger ulnar compartment as a local muscle flap while maintaining the humeral
      compartment as an ulnar deviator and palmar flexor of the wrist. We report two
      cases illustrating the clinical use of the split flexor carpi ulnaris as a local
      muscle flap.

PMID- 16906123
TI  - Interest in a methamphetamine intervention among men who have sex with men.

PMID- 16906124
TI  - Early syphilis among men in Connecticut: epidemiologic and spatial patterns.
AB  - OBJECTIVE: The objective of this study was to describe the epidemiology of early
      syphilis among men in Connecticut, a moderate-prevalence region, in 2004. STUDY
      DESIGN: The authors conducted a cross-sectional analysis of health department
      data. RESULTS: Fifty-five cases were reported from 25 different towns. A majority
      of cases (82%) were reported among men who have sex with men, and 22% reported
      coinfection with HIV. Spatial analysis indicated moderate clustering of cases.
      Approximately half of 197 reported sex partners were not from Connecticut,
      including 28% from New York City and 20% from other states/countries. The median
      distance between partners was 48 km (30 miles). Twenty-three percent of syphilis
      cases had both local and nonlocal partners. CONCLUSIONS: The current epidemiology
      of early syphilis in Connecticut is consistent with national trends. However, the
      dispersal of cases throughout the state and the high proportion of reported sex
      partners residing outside of Connecticut suggest that this state is not a core
      area of endemic transmission.

PMID- 16906125
TI  - Cerebrospinal fluid tau protein is increased in neurosyphilis: a discrimination
      from syphilis without nervous system involvement?
AB  - OBJECTIVE: The objective of this study was to investigate the levels of tau
      protein in neurosyphilis. STUDY DESIGN: Total tau protein in the cerebrospinal
      fluid of 12 patients with neurosyphilis, 17 with syphilis without nervous system
      involvement, 14 controls, and 14 patients with Alzheimer disease of comparable
      age were analyzed. Double-sandwich enzyme-linked immunosorbent assay was used for
      measurements. RESULTS: Increased levels of cerebrospinal fluid total tau were
      observed in neurosyphilis (median [25th-75th percentile]: 349 pg/mL [312-429])
      and in Alzheimer disease (543 [441-1017]) as compared with the controls (189 [106
      220]) and syphilis without nervous system involvement (190 [160-223]). Using a
      cutoff level of 300 pg/mL, increased tau discriminated cases of neurosyphilis
      from syphilis without nervous system involvement with a sensitivity and
      specificity of 83% and 94%, respectively. CONCLUSIONS: These results indicate
      that increased total tau may be useful in the discrimination of neurosyphilis
      from syphilis without nervous system involvement.

PMID- 16906126
TI  - Rectal microbicide acceptability: results of a volume escalation trial.
AB  - OBJECTIVES: The objectives of this study were to determine what volume of a
      microbicide placebo gel is acceptable when applied intrarectally before receptive
      anal intercourse (RAI); and to evaluate responses to properties of the gel, its
      application, and its use. STUDY DESIGN: HIV-uninfected men who reported
      unprotected RAI with serodiscordant or unknown-status partners were enrolled in a
      volume escalation trial. RESULTS: Up to 35 mL of gel with the physical properties
      of Femglide (transparent and odorless) was acceptable to the majority of
      participants. Choice of different levels of viscosity may be needed. For some
      men, volumes judged acceptable when tried without intercourse were not acceptable
      when used during sex. Overall, participants reported high intentions to use
      microbicides when available. Condom use was inconsistent despite advice to use
      condoms. CONCLUSIONS: Microbicides that would require up to 35 mL of volume to be
      effective would be acceptable to men who engage in high-risk RAI.

PMID- 16906127
TI  - G-protein-coupled receptors: evolving views on physiological signalling:
      symposium on G-protein-coupled receptors: evolving concepts and new techniques.

PMID- 16906129
TI  - Formation of GW bodies is a consequence of microRNA genesis.
AB  - GW bodies (GWBs), or mammalian P bodies, proposed to be involved in messenger RNA
      storage and/or degradation, have recently been linked to RNA interference and
      microRNA (miRNA) processing. We report that endogenous let-7 miRNA co
      precipitates with the GW182 protein complex. In addition, knockdown of two
      proteins, Drosha and its protein partner DGCR8, which are vital to the generation
      of mature miRNA, results in the loss of GWBs. Subsequent introduction of short
      interference RNA specific to lamin A/C is accompanied by reassembly of GWBs and
      concurrent knockdown of lamin A/C protein. Taken together, these studies show
      that miRNAs are crucial components in GWB formation.

PMID- 16906128
TI  - Abeta42-driven cerebral amyloidosis in transgenic mice reveals early and robust
      pathology.
AB  - We have generated a novel transgenic mouse model on a C57BL/6J genetic background
      that coexpresses KM670/671NL mutated amyloid precursor protein and L166P mutated
      presenilin 1 under the control of a neuron-specific Thy1 promoter element (APPPS1
      mice). Cerebral amyloidosis starts at 6-8 weeks and the ratio of human amyloid
      (A)beta42 to Abeta40 is 1.5 and 5 in pre-depositing and amyloid-depositing mice,
      respectively. Consistent with this ratio, extensive congophilic parenchymal
      amyloid but minimal amyloid angiopathy is observed. Amyloid-associated
      pathologies include dystrophic synaptic boutons, hyperphosphorylated tau-positive
      neuritic structures and robust gliosis, with neocortical microglia number
      increasing threefold from 1 to 8 months of age. Global neocortical neuron loss is
      not apparent up to 8 months of age, but local neuron loss in the dentate gyrus is
      observed. Because of the early onset of amyloid lesions, the defined genetic
      background of the model and the facile breeding characteristics, APPPS1 mice are
      well suited for studying therapeutic strategies and the pathomechanism of
      amyloidosis by cross-breeding to other genetically engineered mouse models.

PMID- 16906131
TI  - A novel human artificial chromosome gene expression system using herpes simplex
      virus type 1 vectors.
AB  - Human artificial chromosome (HAC) vectors are an important gene transfer system
      for expression and complementation studies. We describe a significant advance in
      HAC technology using infectious herpes simplex virus type 1 (HSV-1) amplicon
      vectors for delivery. This highly efficient method has allowed gene-expressing
      HACs to be established in glioma-, kidney- and lung-derived cells. We also
      developed an HSV-1 hypoxanthine phosphoribosyltransferase (HPRT) HAC vector,
      which generated functional HPRT-expressing HACs that complemented the genetic
      deficiency in human cells. The transduction efficiency of the HSV-1 HAC amplicons
      is several orders of magnitude higher than lipofection-mediated delivery. Studies
      on HAC stability between cell types showed important differences that have
      implications for HAC development and gene expression in human cells. This is the
      first report of establishing gene-expressing HACs in human cells by using an
      efficient, high-capacity viral vector and by identifying factors that are
      involved in cell-type-specific HAC instability. The work is a significant advance
      for HAC technology and the development of HAC gene expression systems in human
      cells.

PMID- 16906132
TI  - Loss of heterozygosity at 15q21.3 correlates with occurrence of metastases in
      head and neck cancer.
AB  - Deletions on the long arm of chromosome 15 suggesting the presence of potential
      tumor suppressor genes have been found in several tumors including carcinomas of
      the colorectum, urinary bladder, breast, lung, and head and neck. Here, we
      analyzed allelic imbalance on chromosome 15q in head and neck carcinomas and
      corresponding lymph node metastases to define common regions of aberrations with
      potential involvement in development and progression of these tumors. We studied
      a panel of 40 polymorphic microsatellite markers, spanning 15q13-15q26, in 63
      head and neck carcinomas and 38 lymph node metastases. Loss of heterozygosity
      (LOH) could be demonstrated in 34 primary tumors (54%) and 35 metastases (92%).
      Aberration mapping defined three minimum regions of aberrations: a region between
      the markers D15S106 and D15S1029 in 15q21.3 (estimated as 3.9 Mb; region 1) was
      affected in the majority of tumors, whereas two other regions between D15S144 and
      D15S1040 in 15q13.3-14 (estimated as 2.4 Mb; region 2) and between D15S130 and
      D15S985 in 15q26.2-26.3 (estimated as 4.7 Mb; region 3) were less often involved.
      Allelic loss in region 1 correlated with T stages (P=0.0029) and metastatic
      potential (P=0.0018). LOH in regions 2 and 3 occurred predominantly in metastases
      (P=0.0129 and P=0.0013, respectively). No correlation with grading, localization,
      or clinical outcome could be established for any of the affected regions. Our
      data hint at aberrations in 15q21.3 as a possible important characteristic for
      head and neck squamous cell carcinomas with risk of progression.

PMID- 16906130
TI  - Cytochrome c-d regulates developmental apoptosis in the Drosophila retina.
AB  - The role of cytochrome c (Cyt c) in caspase activation has largely been
      established from mammalian cell-culture studies, but much remains to be learned
      about its physiological relevance in situ. The role of Cyt c in invertebrates has
      been subject to considerable controversy. The Drosophila genome contains distinct
      cyt c genes: cyt c-p and cyt c-d. Loss of cyt c-p function causes embryonic
      lethality owing to a requirement of the gene for mitochondrial respiration. By
      contrast, cyt c-d mutants are viable but male sterile. Here, we show that cyt c-d
      regulates developmental apoptosis in the pupal eye. cyt c-d mutant retinas show a
      profound delay in the apoptosis of superfluous interommatidial cells and
      perimeter ommatidial cells. Furthermore, there is no apoptosis in mutant retinal
      tissues for the Drosophila homologues of apoptotic protease-activating factor 1
      (Ark) and caspase 9 (Dronc). In addition, we found that cyt c-d--as with ark and
      dronc-regulates scutellar bristle number, which is known to depend on caspase
      activity. Collectively, our results indicate a role of Cyt c in caspase
      regulation of Drosophila somatic cells.

PMID- 16906133
TI  - Autophosphorylation at serine 1987 is dispensable for murine Atm activation in
      vivo.
AB  - The ATM (ataxia telangiectasia mutated) protein kinase is activated under
      physiological and pathological conditions that induce DNA double-strand breaks
      (DSBs). Loss of ATM or failure of its activation in humans and mice lead to
      defective cellular responses to DSBs, such as cell cycle checkpoints, radiation
      sensitivity, immune dysfunction, infertility and cancer predisposition. A widely
      used biological marker to identify the active form of ATM is the
      autophosphorylation of ATM at a single, conserved serine residue (Ser 1981 in
      humans; Ser 1987 in mouse). Here we show that Atm-dependent responses are
      functional at the organismal and cellular level in mice that express a mutant
      form of Atm (mutation of Ser to Ala at position 1987) as their sole Atm species.
      Moreover, the mutant protein does not exhibit dominant-negative interfering
      activity when expressed physiologically or overexpressed in the context of Atm
      heterozygous mice. These results suggest an alternative mode for stimulation of
      Atm by DSBs in which Atm autophosphorylation at Ser 1987, like trans
      phosphorylation of downstream substrates, is a consequence rather than a cause of
      Atm activation.

PMID- 16906134
TI  - Editing-defective tRNA synthetase causes protein misfolding and
      neurodegeneration.
AB  - Misfolded proteins are associated with several pathological conditions including
      neurodegeneration. Although some of these abnormally folded proteins result from
      mutations in genes encoding disease-associated proteins (for example, repeat
      expansion diseases), more general mechanisms that lead to misfolded proteins in
      neurons remain largely unknown. Here we demonstrate that low levels of mischarged
      transfer RNAs (tRNAs) can lead to an intracellular accumulation of misfolded
      proteins in neurons. These accumulations are accompanied by upregulation of
      cytoplasmic protein chaperones and by induction of the unfolded protein response.
      We report that the mouse sticky mutation, which causes cerebellar Purkinje cell
      loss and ataxia, is a missense mutation in the editing domain of the alanyl-tRNA
      synthetase gene that compromises the proofreading activity of this enzyme during
      aminoacylation of tRNAs. These findings demonstrate that disruption of
      translational fidelity in terminally differentiated neurons leads to the
      accumulation of misfolded proteins and cell death, and provide a novel mechanism
      underlying neurodegeneration.

PMID- 16906136
TI  - NMDA-receptor-mediated, cell-specific integration of new neurons in adult dentate
      gyrus.
AB  - New neurons are continuously integrated into existing neural circuits in adult
      dentate gyrus of the mammalian brain. Accumulating evidence indicates that these
      new neurons are involved in learning and memory. A substantial fraction of newly
      born neurons die before they mature and the survival of new neurons is regulated
      in an experience-dependent manner, raising the possibility that the selective
      survival or death of new neurons has a direct role in a process of learning and
      memory--such as information storage--through the information-specific
      construction of new circuits. However, a critical assumption of this hypothesis
      is that the survival or death decision of new neurons is information-specific.
      Because neurons receive their information primarily through their input synaptic
      activity, we investigated whether the survival of new neurons is regulated by
      input activity in a cell-specific manner. Here we developed a retrovirus
      mediated, single-cell gene knockout technique in mice and showed that the
      survival of new neurons is competitively regulated by their own NMDA-type
      glutamate receptor during a short, critical period soon after neuronal birth.
      This finding indicates that the survival of new neurons and the resulting
      formation of new circuits are regulated in an input-dependent, cell-specific
      manner. Therefore, the circuits formed by new neurons may represent information
      associated with input activity within a short time window in the critical period.
      This information-specific addition of new circuits through selective survival or
      death of new neurons may be a unique attribute of new neurons that enables them
      to play a critical role in learning and memory.

PMID- 16906135
TI  - The tumour suppressor Hippo acts with the NDR kinases in dendritic tiling and
      maintenance.
AB  - Precise patterning of dendritic fields is essential for neuronal circuit
      formation and function, but how neurons establish and maintain their dendritic
      fields during development is poorly understood. In Drosophila class IV dendritic
      arborization neurons, dendritic tiling, which allows for the complete but non
      overlapping coverage of the dendritic fields, is established through a 'like
      repels-like' behaviour of dendrites mediated by Tricornered (Trc), one of two NDR
      (nuclear Dbf2-related) family kinases in Drosophila. Here we report that the
      other NDR family kinase, the tumour suppressor Warts/Lats (Wts), regulates the
      maintenance of dendrites; in wts mutants, dendrites initially tile the body wall
      normally, but progressively lose branches at later larval stages, whereas the
      axon shows no obvious defects. We further provide biochemical and genetic
      evidence for the tumour suppressor kinase Hippo (Hpo) as an upstream regulator of
      Wts and Trc for dendrite maintenance and tiling, respectively, thereby revealing
      important functions of tumour suppressor genes of the Hpo signalling pathway in
      dendrite morphogenesis.

PMID- 16906137
TI  - Highly ordered arrangement of single neurons in orientation pinwheels.
AB  - In the visual cortex of higher mammals, neurons are arranged across the cortical
      surface in an orderly map of preferred stimulus orientations. This map contains
      'orientation pinwheels', structures that are arranged like the spokes of a wheel
      such that orientation changes continuously around a centre. Conventional optical
      imaging first demonstrated these pinwheels, but the technique lacked the spatial
      resolution to determine the response properties and arrangement of cells near
      pinwheel centres. Electrophysiological recordings later demonstrated sharply
      selective neurons near pinwheel centres, but it remained unclear whether they
      were arranged randomly or in an orderly fashion. Here we use two-photon calcium
      imaging in vivo to determine the microstructure of pinwheel centres in cat visual
      cortex with single-cell resolution. We find that pinwheel centres are highly
      ordered: neurons selective to different orientations are clearly segregated even
      in the very centre. Thus, pinwheel centres truly represent singularities in the
      cortical map. This highly ordered arrangement at the level of single cells
      suggests great precision in the development of cortical circuits underlying
      orientation selectivity.

PMID- 16906138
TI  - Molecular biology: sticky end in protein synthesis.

PMID- 16906139
TI  - A new view of the onset of plasticity during the nanoindentation of aluminium.
AB  - In nanoscale contact experiments, it is generally believed that the shear stress
      at the onset of plasticity can approach the theoretical shear strength of an
      ideal, defect-free lattice, a trend also observed in idealized molecular dynamics
      simulations. Here we report direct evidence that plasticity in a dislocation-free
      volume of polycrystalline aluminium can begin at very small forces, remarkably,
      even before the first sustained rise in repulsive force. However, the shear
      stresses associated with these very small forces do approach the theoretical
      shear strength of aluminium (approximately 2.2 GPa). Our observations entail
      correlating quantitative load-displacement measurements with individual video
      frames acquired during in situ nanoindentation experiments in a transmission
      electron microscope. We also report direct evidence that a submicrometre grain of
      aluminium plastically deformed by nanoindentation to a dislocation density of
      approximately 10(14) m(-2) is also capable of supporting shear stresses close to
      the theoretical shear strength. This result is contrary to earlier assumptions
      that a dislocation-free volume is necessary to achieve shear stresses near the
      theoretical shear strength of the material. Moreover, our results in entirety are
      at odds with the prevalent notion that the first obvious displacement excursion
      in a nanoindentation test is indicative of the onset of plastic deformation.

PMID- 16906140
TI  - Enhanced magnetic field sensitivity of spin-dependent transport in cluster
      assembled metallic nanostructures.
AB  - The emerging field of spintronics explores the many possibilities offered by the
      prospect of using the spin of the electrons for fast, nanosized electronic
      devices. The effect of magnetization acting on a current is the essence of giant
      or tunnel magnetoresistance. Although such spintronics effects already find
      technological applications, much of the underlying physics remains to be
      explored. The aim of this article is to demonstrate the importance of spin mixing
      in metallic nanostructures. Here we show that magnetic clusters embedded in a
      metallic matrix exhibit a giant magnetic response of more than 500% at low
      temperature, using a recently developed thermoelectric measurement. This method
      eliminates the dominating resistivity component of the magnetic response and thus
      reveals an intrinsic spin-dependent process: the conduction-electron spin
      precession about the exchange field as the electron crosses the clusters, giving
      rise to a spin-mixing mechanism with strong field dependence. This effect appears
      sensibly only in the smallest clusters, that is, at the level of less than 100
      atoms per cluster.

PMID- 16906141
TI  - Time-resolved electrostatic force microscopy of polymer solar cells.
AB  - Blends of conjugated polymers with fullerenes, polymers, or nanocrystals make
      promising materials for low-cost photovoltaic applications. Different processing
      conditions affect the efficiencies of these solar cells by creating a variety of
      nanostructured morphologies, however, the relationship between film structure and
      device efficiency is not fully understood. We introduce time-resolved
      electrostatic force microscopy (EFM) as a means to measure photoexcited charge in
      polymer films with a resolution of 100 nm and 100 micros. These EFM measurements
      correlate well with the external quantum efficiencies measured for a series of
      polymer photodiodes, providing a direct link between local morphology, local
      optoelectronic properties and device performance. The data show that the domain
      centres account for the majority of the photoinduced charge collected in
      polyfluorene blend devices. These results underscore the importance of
      controlling not only the length scale of phase separation, but also the
      composition of the domains when optimizing nanostructured solar cells.

PMID- 16906142
TI  - Electrochemical lithiation synthesis of nanoporous materials with superior
      catalytic and capacitive activity.
AB  - Nanoporous materials have attracted great technological interest during the past
      two decades, essentially due to their wide range of applications: they are used
      as catalysts, molecular sieves, separators and gas sensors as well as for
      electronic and electrochemical devices. Most syntheses of nanoporous materials
      reported so far have focused on template-assisted bottom-up processes, including
      soft templating (chelating agents, surfactants, block copolymers and so on) and
      hard templating (porous alumina, carbon nanotubes and nanoporous materials)
      methods. Here, we exploit a mechanism implicitly occurring in lithium batteries
      at deep discharge to develop it into a room-temperature template-free method of
      wide applicability in the synthesis of not only transition metals but also metal
      oxides with large surface area and pronounced nanoporosity associated with
      unprecedented properties. The power of this top-down method is demonstrated by
      the synthesis of nanoporous Pt and RuO2, both exhibiting superior performance:
      the Pt prepared shows outstanding properties when used as an electrocatalyst for
      methanol oxidation, and the RuO2, when used as a supercapacitor electrode
      material, exhibits a distinctly better performance than that previously reported
      for non-hydrated RuO2 (refs 19,20).

PMID- 16906143
TI  - Essential CDK1-inhibitory role for separase during meiosis I in vertebrate
      oocytes.
AB  - Separase not only triggers anaphase of meiosis I by proteolytic cleavage of
      cohesin on chromosome arms, but in vitro vertebrate separase also acts as a
      direct inhibitor of cyclin-dependent kinase 1 (Cdk1) on liberation from the
      inhibitory protein, securin. Blocking separase-Cdk1 complex formation by
      microinjection of anti-separase antibodies prevents polar-body extrusion in
      vertebrate oocytes. Importantly, proper meiotic maturation is rescued by chemical
      inhibition of Cdk1 or expression of Cdk1-binding separase fragments lacking
      cohesin-cleaving activity.

PMID- 16906144
TI  - The Legionella pneumophila effector protein DrrA is a Rab1 guanine nucleotide
      exchange factor.
AB  - The intracellular pathogen Legionella pneumophila avoids fusion with lysosomes
      and subverts membrane transport from the endoplasmic reticulum to create an
      organelle that supports bacterial replication. Transport of endoplasmic reticulum
      derived vesicles to the Legionella-containing vacuole (LCV) requires bacterial
      proteins that are translocated into host cells by a type IV secretion apparatus
      called Dot/Icm. Recent observations have revealed recruitment of the host GTPase
      Rab1 to the LCV by a process requiring the Dot/Icm system. Here, a visual screen
      was used to identify L. pneumophila mutants with defects in Rab1 recruitment. One
      of the factors identified in this screen was DrrA, a new Dot/Icm substrate
      protein translocated into host cells. We show that DrrA is a potent and highly
      specific Rab1 guanine nucleotide-exchange factor (GEF). DrrA can disrupt Rab1
      mediated secretory transport to the Golgi apparatus by competing with endogenous
      exchange factors to recruit and activate Rab1 on plasma membrane-derived
      organelles. These data establish that intracellular pathogens have the capacity
      to directly modulate the activation state of a specific member of the Rab family
      of GTPases and thus further our understanding of the mechanisms used by bacterial
      pathogens to manipulate host vesicular transport.

PMID- 16906145
TI  - Yeast kinesin-8 depolymerizes microtubules in a length-dependent manner.
AB  - The microtubule cytoskeleton and the mitotic spindle are highly dynamic
      structures, yet their sizes are remarkably constant, thus indicating that the
      growth and shrinkage of their constituent microtubules are finely balanced. This
      balance is achieved, in part, through kinesin-8 proteins (such as Kip3p in
      budding yeast and KLP67A in Drosophila) that destabilize microtubules. Here, we
      directly demonstrate that Kip3p destabilizes microtubules by depolymerizing them-
      accounting for the effects of kinesin-8 perturbations on microtubule and spindle
      length observed in fungi and metazoan cells. Furthermore, using single-molecule
      microscopy assays, we show that Kip3p has several properties that distinguish it
      from other depolymerizing kinesins, such as the kinesin-13 MCAK. First, Kip3p
      disassembles microtubules exclusively at the plus end and second, remarkably,
      Kip3p depolymerizes longer microtubules faster than shorter ones. These
      properties are consequences of Kip3p being a highly processive, plus-end-directed
      motor, both in vitro and in vivo. Length-dependent depolymerization provides a
      new mechanism for controlling the lengths of subcellular structures.

PMID- 16906146
TI  - Proteasome recruitment and activation of the Uch37 deubiquitinating enzyme by
      Adrm1.
AB  - Uch37 is one of the three principal deubiquitinating enzymes (DUBs), and the only
      ubiquitin carboxy-terminal hydrolase (UCH)-family protease, that is associated
      with mammalian proteasomes. We show that Uch37 is responsible for the ubiquitin
      isopeptidase activity in the PA700 (19S) proteasome regulatory complex. PA700
      isopeptidase disassembles Lys 48-linked polyubiquitin specifically from the
      distal end of the chain, a property that may be used to clear poorly
      ubiquitinated or unproductively bound substrates from the proteasome. To better
      understand Uch37 function and the mechanism responsible for its specificity, we
      investigated how Uch37 is recruited to proteasomes. Uch37 binds through Adrm1, a
      previously unrecognized orthologue of Saccharomyces cerevisiae Rpn13p, which in
      turn is bound to the S1 (also known as Rpn2) subunit of the 19S complex. Adrm1
      (human Rpn13, hRpn13) binds the carboxy-terminal tail of Uch37, a region that is
      distinct from the UCH catalytic domain, which we show inhibits Uch37 activity.
      Following binding, Adrm1 relieves Uch37 autoinhibition, accelerating the
      hydrolysis of ubiquitin-7-amido-4-methylcoumarin (ubiquitin-AMC). However,
      neither Uch37 alone nor the Uch37-Adrm1 or Uch37-Adrm1-S1 complexes can hydrolyse
      di-ubiquitin efficiently; rather, incorporation into the 19S complex is required
      to enable processing of polyubiquitin chains.

PMID- 16906147
TI  - PIASy mediates NEMO sumoylation and NF-kappaB activation in response to genotoxic
      stress.
AB  - Protein modification by SUMO (small ubiquitin-like modifier) is an important
      regulatory mechanism for multiple cellular processes. SUMO-1 modification of NEMO
      (NF-kappaB essential modulator), the IkappaB kinase (IKK) regulatory subunit, is
      critical for activation of NF-kappaB by genotoxic agents. However, the SUMO
      ligase, and the mechanisms involved in NEMO sumoylation, remain unknown. Here, we
      demonstrate that although small interfering RNAs (siRNAs) against PIASy (protein
      inhibitor of activated STATy) inhibit NEMO sumoylation and NF-kappaB activation
      in response to genotoxic agents, overexpression of PIASy enhances these events.
      PIASy preferentially stimulates site-selective modification of NEMO by SUMO-1,
      but not SUMO-2 and SUMO-3, in vitro. PIASy-NEMO interaction is increased by
      genotoxic stress and occurs in the nucleus in a manner mutually exclusive with
      IKK interaction. In addition, hydrogen peroxide (H2O2) also increases PIASy-NEMO
      interaction and NEMO sumoylation, whereas antioxidants prevent these events
      induced by DNA-damaging agents. Our findings demonstrate that PIASy is the first
      SUMO ligase for NEMO whose substrate specificity seems to be controlled by IKK
      interaction, subcellular targeting and oxidative stress conditions.

PMID- 16906148
TI  - Plus end-specific depolymerase activity of Kip3, a kinesin-8 protein, explains
      its role in positioning the yeast mitotic spindle.
AB  - The budding yeast protein Kip3p is a member of the conserved kinesin-8 family of
      microtubule motors, which are required for microtubule-cortical interactions,
      normal spindle assembly and kinetochore dynamics. Here, we demonstrate that Kip3p
      is both a plus end-directed motor and a plus end-specific depolymerase--a unique
      combination of activities not found in other kinesins. The ATPase activity of
      Kip3p was activated by both microtubules and unpolymerized tubulin. Furthermore,
      Kip3p in the ATP-bound state formed a complex with unpolymerized tubulin. Thus,
      motile kinesin-8s may depolymerize microtubules by a mechanism that is similar to
      that used by non-motile kinesin-13 proteins. Fluorescent speckle analysis
      established that, in vivo, Kip3p moved toward and accumulated on the plus ends of
      growing microtubules, suggesting that motor activity brings Kip3p to its site of
      action. Globally, and more dramatically on cortical contact, Kip3p promoted
      catastrophes and pausing, and inhibited microtubule growth. These findings
      explain the role of Kip3p in positioning the mitotic spindle in budding yeast and
      potentially other processes controlled by kinesin-8 family members.

PMID- 16906149
TI  - STIM1 carboxyl-terminus activates native SOC, I(crac) and TRPC1 channels.
AB  - Receptor-evoked Ca2+ signalling involves Ca2+ release from the endoplasmic
      reticulum, followed by Ca2+ influx across the plasma membrane. Ca2+ influx is
      essential for many cellular functions, from secretion to transcription, and is
      mediated by Ca2+-release activated Ca2+ (I(crac)) channels and store-operated
      calcium entry (SOC) channels. Although the molecular identity and regulation of
      I(crac) and SOC channels have not been precisely determined, notable recent
      findings are the identification of STIM1, which has been indicated to regulate
      SOC and I(crac) channels by functioning as an endoplasmic reticulum Ca2+ sensor,
      and ORAI1 (ref. 7) or CRACM1 (ref. 8)--both of which may function as I(crac)
      channels or as an I(crac) subunit. How STIM1 activates the Ca2+ influx channels
      and whether STIM1 contributes to the channel pore remains unknown. Here, we
      identify the structural features that are essential for STIM1-dependent
      activation of SOC and I(crac) channels, and demonstrate that they are identical
      to those involved in the binding and activation of TRPC1. Notably, the cytosolic
      carboxyl terminus of STIM1 is sufficient to activate SOC, I(crac) and TRPC1
      channels even when native STIM1 is depleted by small interfering RNA. Activity of
      STIM1 requires an ERM domain, which mediates the selective binding of STIM1 to
      TRPC1, 2 and 4, but not to TRPC3, 6 or 7, and a cationic lysine-rich region,
      which is essential for gating of TRPC1. Deletion of either region in the
      constitutively active STIM1(D76A) yields dominant-negative mutants that block
      native SOC channels, expressed TRPC1 in HEK293 cells and I(crac) in Jurkat cells.
      These observations implicate STIM1 as a key regulator of activity rather than a
      channel component, and reveal similar regulation of SOC, I(crac) and TRPC channel
      activation by STIM1.

PMID- 16906150
TI  - Ceruloplasmin is a NO oxidase and nitrite synthase that determines endocrine NO
      homeostasis.
AB  - Nitrite represents a bioactive reservoir of nitric oxide (NO) that may modulate
      vasodilation, respiration and cytoprotection after ischemia-reperfusion injury.
      Although nitrite formation is thought to occur via reaction of NO with oxygen,
      this third-order reaction cannot compete kinetically with the reaction of NO with
      hemoglobin to form nitrate. Indeed, the formation of nitrite from NO in the blood
      is limited when plasma is substituted with physiological buffers, which suggests
      that plasma contains metal-based enzymatic pathways for nitrite synthesis. We
      therefore hypothesized that the multicopper oxidase, ceruloplasmin, could oxidize
      NO to NO+, with subsequent hydration to nitrite. Accordingly, plasma NO oxidase
      activity was decreased after ceruloplasmin immunodepletion, in ceruloplasmin
      knockout mice and in people with congenital aceruloplasminemia. Compared to
      controls, plasma nitrite concentrations were substantially reduced in
      ceruloplasmin knockout mice, which were more susceptible to liver infarction
      after ischemia and reperfusion. The extent of hepatocellular infarction
      normalized after nitrite repletion. These data suggest new functions for the
      multicopper oxidases in endocrine NO homeostasis and nitrite synthesis, and they
      support the hypothesis that physiological concentrations of nitrite contribute to
      hypoxic signaling and cytoprotection.

PMID- 16906151
TI  - Biosynthesis of Dictyostelium discoideum differentiation-inducing factor by a
      hybrid type I fatty acid-type III polyketide synthase.
AB  - Differentiation-inducing factors (DIFs) are well known to modulate formation of
      distinct communal cell types from identical Dictyostelium discoideum amoebas, but
      DIF biosynthesis remains obscure. We report complimentary in vivo and in vitro
      experiments identifying one of two approximately 3,000-residue D. discoideum
      proteins, termed 'steely', as responsible for biosynthesis of the DIF
      acylphloroglucinol scaffold. Steely proteins possess six catalytic domains
      homologous to metazoan type I fatty acid synthases (FASs) but feature an
      iterative type III polyketide synthase (PKS) in place of the expected FAS C
      terminal thioesterase used to off load fatty acid products. This new domain
      arrangement likely facilitates covalent transfer of steely N-terminal acyl
      products directly to the C-terminal type III PKS active sites, which catalyze
      both iterative polyketide extension and cyclization. The crystal structure of a
      steely C-terminal domain confirms conservation of the homodimeric type III PKS
      fold. These findings suggest new bioengineering strategies for expanding the
      scope of fatty acid and polyketide biosynthesis.

PMID- 16906152
TI  - Deletion of the background potassium channel TREK-1 results in a depression
      resistant phenotype.
AB  - Depression is a devastating illness with a lifetime prevalence of up to 20%. The
      neurotransmitter serotonin or 5-hydroxytryptamine (5-HT) is involved in the
      pathophysiology of depression and in the effects of antidepressant treatments.
      However, molecular alterations that underlie the pathology or treatment of
      depression are still poorly understood. The TREK-1 protein is a background K+
      channel regulated by various neurotransmitters including 5-HT. In mice, the
      deletion of its gene (Kcnk2, also called TREK-1) led to animals with an increased
      efficacy of 5-HT neurotransmission and a resistance to depression in five
      different models and a substantially reduced elevation of corticosterone levels
      under stress. TREK-1-deficient (Kcnk2-/-) mice showed behavior similar to that of
      naive animals treated with classical antidepressants such as fluoxetine. Our
      results indicate that alterations in the functioning, regulation or both of the
      TREK-1 channel may alter mood, and that this particular K+ channel may be a
      potential target for new antidepressants.

PMID- 16906153
TI  - Dynamic shifts of visual receptive fields in cortical area MT by spatial
      attention.
AB  - Voluntary attention is the top-down selection process that focuses cortical
      processing resources on the most relevant sensory information. Spatial attention-
      that is, selection based on stimulus position--alters neuronal responsiveness
      throughout primate visual cortex. It has been hypothesized that it also changes
      receptive field profiles by shifting their centers toward attended locations and
      by shrinking them around attended stimuli. Here we examined, at high resolution,
      receptive fields in cortical area MT of rhesus macaque monkeys when their
      attention was directed to different locations within and outside these receptive
      fields. We found a shift of receptive fields, even far from the current location
      of attention, accompanied by a small amount of shrinkage. Thus, already in early
      extrastriate cortex, receptive fields are not static entities but are highly
      modifiable, enabling the dynamic allocation of processing resources to attended
      locations and supporting enhanced perception within the focus of attention by
      effectively increasing the local cortical magnification.

PMID- 16906154
TI  - NR4A orphan nuclear receptors are transcriptional regulators of hepatic glucose
      metabolism.
AB  - Hepatic glucose production is crucial for glucose homeostasis, and its
      dysregulation contributes to the pathogenesis of diabetes. Here, we show that
      members of the NR4A family of ligand-independent orphan nuclear receptors are
      downstream mediators of cAMP action in the hormonal control of gluconeogenesis.
      Hepatic expression of Nur77, Nurr1 and NOR1 is induced by the cAMP axis in
      response to glucagon and fasting in vivo and is increased in diabetic mice that
      exhibit elevated gluconeogenesis. Adenoviral expression of Nur77 induces genes
      involved in gluconeogenesis, stimulates glucose production both in vitro and in
      vivo, and raises blood glucose levels. Conversely, expression of an inhibitory
      mutant Nur77 receptor antagonizes gluconeogenic gene expression and lowers blood
      glucose levels in db/db mice. These results outline a previously unrecognized
      role for orphan nuclear receptors in the transcriptional control of glucose
      homeostasis.

PMID- 16906155
TI  - Transfer of a point mutation in Mycobacterium tuberculosis inhA resolves the
      target of isoniazid.
AB  - Isoniazid is one of the most effective antituberculosis drugs, yet its precise
      mechanism of action is still controversial. Using specialized linkage
      transduction, a single point mutation allele (S94A) within the putative target
      gene inhA was transferred in Mycobacterium tuberculosis. The inhA(S94A) allele
      was sufficient to confer clinically relevant levels of resistance to isoniazid
      killing and inhibition of mycolic acid biosynthesis. This resistance correlated
      with the decreased binding of the INH-NAD inhibitor to InhA, as shown by
      enzymatic and X-ray crystallographic analyses, and establishes InhA as the
      primary target of isoniazid action in M. tuberculosis.

PMID- 16906156
TI  - Role of deficient type III interferon-lambda production in asthma exacerbations.
AB  - Rhinoviruses are the major cause of asthma exacerbations, and asthmatics have
      increased susceptibility to rhinovirus and risk of invasive bacterial infections.
      Here we show deficient induction of interferon-lambdas by rhinovirus in asthmatic
      primary bronchial epithelial cells and alveolar macrophages, which was highly
      correlated with severity of rhinovirus-induced asthma exacerbation and virus load
      in experimentally infected human volunteers. Induction by lipopolysaccharide in
      asthmatic macrophages was also deficient and correlated with exacerbation
      severity. These results identify previously unknown mechanisms of susceptibility
      to infection in asthma and suggest new approaches to prevention and/or treatment
      of asthma exacerbations.

PMID- 16906157
TI  - Loss of the tumor suppressor Vhlh leads to upregulation of Cxcr4 and rapidly
      progressive glomerulonephritis in mice.
AB  - Rapidly progressive glomerulonephritis (RPGN) is a clinical syndrome
      characterized by loss of renal function within days to weeks and by glomerular
      crescents on biopsy. The pathogenesis of this disease is unclear, but circulating
      factors are believed to have a major role. Here, we show that deletion of the Von
      Hippel-Lindau gene (Vhlh) from intrinsic glomerular cells of mice is sufficient
      to initiate a necrotizing crescentic glomerulonephritis and the clinical features
      that accompany RPGN. Loss of Vhlh leads to stabilization of hypoxia-inducible
      factor alpha subunits (HIFs). Using gene expression profiling, we identified de
      novo expression of the HIF target gene Cxcr4 (ref. 3) in glomeruli from both mice
      and humans with RPGN. The course of RPGN is markedly improved in mice treated
      with a blocking antibody to Cxcr4, whereas overexpression of Cxcr4 alone in
      podocytes of transgenic mice is sufficient to cause glomerular disease.
      Collectively, these results indicate an alternative mechanism for the
      pathogenesis of RPGN and glomerular disease in an animal model and suggest novel
      molecular pathways for intervention in this disease.

PMID- 16906158
TI  - Probing the activation-promoted structural rearrangements in preassembled
      receptor-G protein complexes.
AB  - Activation of heterotrimeric G proteins by their cognate seven transmembrane
      domain receptors is believed to involve conformational changes propagated from
      the receptor to the G proteins. However, the nature of these changes remains
      unknown. We monitored the conformational rearrangements at the interfaces between
      receptors and G proteins and between G protein subunits by measuring
      bioluminescence resonance energy transfer between probes inserted at multiple
      sites in receptor-G protein complexes. Using the data obtained for the
      alpha(2A)AR-G alpha(i1) beta1gamma2 complex and the available crystal structures
      of G alpha(i1) beta1gamma2, we propose a model wherein agonist binding induces
      conformational reorganization of a preexisting receptor-G protein complex,
      leading the G alpha-G betagamma interface to open but not dissociate. This
      conformational change may represent the movement required to allow nucleotide
      exit from the G alpha subunit, thus reflecting the initial activation event.

PMID- 16906159
TI  - Oligomerization of signaling complexes by the multipoint binding of GRB2 to both
      LAT and SOS1.
AB  - Receptor oligomerization is vital for activating intracellular signaling, in part
      by initiating events that recruit effector and adaptor proteins to sites of
      active signaling. Whether these distal molecules themselves oligomerize is not
      well appreciated. In this study, we examined the molecular interactions of the
      adaptor protein GRB2. In T cells, the SH2 domain of GRB2 binds phosphorylated
      tyrosines on the adaptor protein LAT and the GRB2 SH3 domains associate with the
      proline-rich regions of SOS1 and CBL. Using biochemical and biophysical
      techniques in conjunction with confocal microscopy, we observed that the
      simultaneous association of GRB2, via its SH2 and SH3 domains, with multivalent
      ligands led to the oligomerization of these ligands, which affected signaling.
      These data suggest that multipoint binding of distal adaptor proteins mediates
      the formation of oligomeric signaling clusters vital for intracellular signaling.

PMID- 16906160
TI  - Dynamically driven protein allostery.
AB  - Allosteric interactions are typically considered to proceed through a series of
      discrete changes in bonding interactions that alter the protein conformation.
      Here we show that allostery can be mediated exclusively by transmitted changes in
      protein motions. We have characterized the negatively cooperative binding of cAMP
      to the dimeric catabolite activator protein (CAP) at discrete conformational
      states. Binding of the first cAMP to one subunit of a CAP dimer has no effect on
      the conformation of the other subunit. The dynamics of the system, however, are
      modulated in a distinct way by the sequential ligand binding process, with the
      first cAMP partially enhancing and the second cAMP completely quenching protein
      motions. As a result, the second cAMP binding incurs a pronounced conformational
      entropic penalty that is entirely responsible for the observed cooperativity. The
      results provide strong support for the existence of purely dynamics-driven
      allostery.

PMID- 16906161
TI  - Molecular analysis of flies selected for aggressive behavior.
AB  - Aggressive behavior is pervasive throughout the animal kingdom, and yet very
      little is known about its molecular underpinnings. To address this problem, we
      have developed a population-based selection procedure to increase aggression in
      Drosophila melanogaster. We measured changes in aggressive behavior in the
      selected subpopulations with a new two-male arena assay. In only ten generations
      of selection, the aggressive lines became markedly more aggressive than the
      neutral lines. After 21 generations, the fighting index increased more than 30
      fold. Using microarray analysis, we identified genes with differing expression
      levels in the aggressive and neutral lines as candidates for this strong
      behavioral selection response. We tested a small set of these genes through
      mutant analysis and found that one significantly increased fighting frequency.
      These results suggest that selection for increases in aggression can be used to
      molecularly dissect this behavior.

PMID- 16906162
TI  - Discovery of previously unidentified genomic disorders from the duplication
      architecture of the human genome.
AB  - Genomic disorders are characterized by the presence of flanking segmental
      duplications that predispose these regions to recurrent rearrangement. Based on
      the duplication architecture of the genome, we investigated 130 regions that we
      hypothesized as candidates for previously undescribed genomic disorders. We
      tested 290 individuals with mental retardation by BAC array comparative genomic
      hybridization and identified 16 pathogenic rearrangements, including de novo
      microdeletions of 17q21.31 found in four individuals. Using oligonucleotide
      arrays, we refined the breakpoints of this microdeletion, defining a 478-kb
      critical region containing six genes that were deleted in all four individuals.
      We mapped the breakpoints of this deletion and of four other pathogenic
      rearrangements in 1q21.1, 15q13, 15q24 and 17q12 to flanking segmental
      duplications, suggesting that these are also sites of recurrent rearrangement. In
      common with the 17q21.31 deletion, these breakpoint regions are sites of copy
      number polymorphism in controls, indicating that these may be inherently unstable
      genomic regions.

PMID- 16906163
TI  - Microdeletion encompassing MAPT at chromosome 17q21.3 is associated with
      developmental delay and learning disability.
AB  - Recently, the application of array-based comparative genomic hybridization (array
      CGH) has improved rates of detection of chromosomal imbalances in individuals
      with mental retardation and dysmorphic features. Here, we describe three
      individuals with learning disability and a heterozygous deletion at chromosome
      17q21.3, detected in each case by array CGH. FISH analysis demonstrated that the
      deletions occurred as de novo events in each individual and were between 500 kb
      and 650 kb in size. A recently described 900-kb inversion that suppresses
      recombination between ancestral H1 and H2 haplotypes encompasses the deletion. We
      show that, in each trio, the parent of origin of the deleted chromosome 17
      carries at least one H2 chromosome. This region of 17q21.3 shows complex genomic
      architecture with well-described low-copy repeats (LCRs). The orientation of LCRs
      flanking the deleted segment in inversion heterozygotes is likely to facilitate
      the generation of this microdeletion by means of non-allelic homologous
      recombination.

PMID- 16906164
TI  - A new chromosome 17q21.31 microdeletion syndrome associated with a common
      inversion polymorphism.
AB  - Submicroscopic genomic copy number changes have been identified only recently as
      an important cause of mental retardation. We describe the detection of three
      interstitial, overlapping 17q21.31 microdeletions in a cohort of 1,200 mentally
      retarded individuals associated with a clearly recognizable clinical phenotype of
      mental retardation, hypotonia and a characteristic face. The deletions encompass
      the MAPT and CRHR1 genes and are associated with a common inversion polymorphism.

PMID- 16906165
TI  - Interleukin 18-independent engagement of interleukin 18 receptor-alpha is
      required for autoimmune inflammation.
AB  - T helper type 1 (T(H)1) lymphocytes are considered to be the main pathogenic cell
      type responsible for organ-specific autoimmune inflammation. As interleukin 18
      (IL-18) is a cofactor with IL-12 in promoting T(H)1 cell development, we examined
      the function of IL-18 and its receptor, IL-18R, in autoimmune central nervous
      system inflammation. Similar to IL-12-deficient mice, IL-18-deficient mice were
      susceptible to experimental autoimmune encephalomyelitis. In contrast, IL-18R
      alpha-deficient mice were resistant to experimental autoimmune encephalomyelitis,
      indicating involvement of an IL-18R alpha ligand other than IL-18 with
      encephalitogenic properties. Moreover, engagement of IL-18R alpha on antigen
      presenting cells was required for the generation of pathogenic IL-17-producing T
      helper cells. Thus, IL-18 and T(H)1 cells are dispensable, whereas IL-18R alpha
      and IL-17-producing T helper cells are required, for autoimmune central nervous
      system inflammation.

PMID- 16906166
TI  - Interleukin 27 negatively regulates the development of interleukin 17-producing T
      helper cells during chronic inflammation of the central nervous system.
AB  - Studies have focused on the events that influence the development of interleukin
      17 (IL-17)-producing T helper cells (T(H)-17 cells) associated with autoimmunity,
      such as experimental autoimmune encephalitis, but relatively little is known
      about the cytokines that antagonize T(H)-17 cell effector responses. Here we show
      that IL-27 receptor-deficient mice chronically infected with Toxoplasma gondii
      developed severe neuroinflammation that was CD4+ T cell dependent and was
      associated with a prominent IL-17 response. In vitro, treatment of naive primary
      T cells with IL-27 suppressed the development T(H)-17 cells induced by IL-6 and
      transforming growth factor-beta, which was dependent on the intracellular
      signaling molecule STAT1 but was independent of inhibition of IL-6 signaling
      mediated by the suppressor protein SOCS3. Thus IL-27, a potent inhibitor of T(H)
      17 cell development, may be a useful target for treating inflammatory diseases
      mediated by these cells.

PMID- 16906169
TI  - Interventional pain management in the new millennium.

PMID- 16906167
TI  - Interleukin 27 limits autoimmune encephalomyelitis by suppressing the development
      of interleukin 17-producing T cells.
AB  - Interleukin 27 (IL-27) was first characterized as a proinflammatory cytokine with
      T helper type 1-inducing activity. However, subsequent work has demonstrated that
      mice deficient in IL-27 receptor (IL-27R alpha) show exacerbated inflammatory
      responses to a variety of challenges, suggesting that IL-27 has important
      immunoregulatory functions in vivo. Here we demonstrate that IL-27R alpha
      deficient mice were hypersusceptible to experimental autoimmune encephalomyelitis
      and generated more IL-17-producing T helper cells. IL-27 acted directly on
      effector T cells to suppress the development of IL-17-producing T helper cells
      mediated by IL-6 and transforming growth factor-beta. This suppressive activity
      was dependent on the transcription factor STAT1 and was independent of interferon
      gamma. Finally, IL-27 suppressed IL-6-mediated T cell proliferation. These data
      provide a mechanistic explanation for the IL-27-mediated immune suppression noted
      in several in vivo models of inflammation.

PMID- 16906170
TI  - The role of guidelines in interventional pain medicine: let us separate apples
      and oranges.
AB  - Practice guidelines are not only an ancient tradition, but they are a fact of
      life. The first guidelines were developed in the 1840s, shortly after the use of
      anesthesia was first demonstrated. Even though practice guideline development has
      spawned an impressive and over-aggressive literature of its own, many unanswered
      questions exist with regard not only to practice parameters and guidelines in
      general, but in particular with the application of interventional techniques in
      managing persistent pain. In spite of the great potential of clinical practice
      guidelines, and the involvement of numerous medical societies and physician
      groups, there is still a great debate within the profession not only about the
      pros and cons of the development and usage of the guidelines, but also
      conflicting and controversial opinions on both sides of the issue, i.e.,
      providers and patients vs payors. This article discusses the development, usage,
      advantages, disadvantages and the implications of practice guidelines to
      interventional pain medicine specialists.

PMID- 16906172
TI  - Thoracic spine spasms secondary to hemorrhagic intestinal ulcer.
AB  - A case of thoracic spine spasms secondary to a bleeding duodenal ulcer is
      presented. A 41-year-old male with 14-week history of thoracic spine spasm was
      treated with bed rest, spinal manipulation, physical therapy, medication, and a
      thoracolumbar brace. Subsequently, a provocative thoracic discogram performed at
      T9-T10 created periscapular pain and also reproduced the presenting thoracic
      spasms. Intradiscal electrothermal annuloplasty (IDET) was performed at the T9
      T10 level, but without sustained relief. The patient presented to a spine center
      for evaluation. The diagnosis of thoracic discogenic disease was suspected. A
      second provocative thoracic discogram was performed and failed to reproduce his
      thoracic spasms. Three weeks after being referred to a chronic pain management
      physician, the patient presented to a local emergency room with hema-temesis. An
      endoscopic evaluation revealed a bleeding duodenal ulcer. Following medical
      treatment of the duodenal ulcer with a proton pump inhibitor the patient had
      complete resolution of his thoracic spasms. This represents the first reported
      case of thoracic spine spasms as an initial presenting symptom of a bleeding
      peptic ulcer.

PMID- 16906171
TI  - Interventional techniques in the management of chronic pain: Part 2.0.
AB  - The practice guidelines for interventional techniques in the management of
      chronic pain are systematically developed statements to assist physician and
      patient decisions about appropriate health care related to chronic pain. These
      guidelines are professionally derived recommendations for practices in the
      diagnosis and treatment of chronic or persistent pain. They were developed
      utilizing a combination of evidence and consensus based techniques, to increase
      patient access to treatment, improve outcomes and appropriateness of care, and
      optimize cost-effectiveness. The guidelines include a discussion of their
      purpose, rationale, and importance, including the patient population served, the
      methodology and the pathophysiologic basis for intervention. Various
      interventional techniques will be discussed addressing the rationale for their
      use in chronic pain with analysis of the outcomes data and cost effectiveness.
      These guidelines do not constitute inflexible treatment recommendations. It is
      expected that a provider will establish a plan of care on a case-by-case basis,
      taking into account an individual patient's medical condition, personal needs,
      and preferences, and the physician's experience. Based on an individual patient's
      needs, treatment different from that outlined here could be warranted.

PMID- 16906174
TI  - Implications of model compliance program for interventional pain physicians.
AB  - The model compliance program for small physician practices, recently released by
      the Office of the Inspector General (OIG) shows a remarkable degree of
      flexibility reflective of the OIG's acknowledgment that small physician practices
      have such limited resources that they might not be in a position to implement a
      full compliance program. The OIG suggests a step by step approach to the
      implementation of a compliance program which includes auditing and monitoring,
      establishing practice standards and procedures, designating na compliance officer
      or contact, conducting training and education, responding to offenses and
      corrective actions, opening uses of communication, and enforcing discipline
      through well published guidelines. The OIG's final plan also lists a wide variety
      of risk areas that a small practice should address in its program, many of the
      identified risk areas relate to situations in which physicians interact with
      other types of providers-including durable medical equipment suppliers, home
      health agencies, clinical laboratories, hospitals, and others. Although
      physicians have tended to equate the term "compliance" with "billing and coding"
      compliance, the OIG's list of risk areas reveals a much broader range of
      compliance issues and concerns, with particular emphasis on financial
      relationships between physicians and other providers. In conclusion, Physician
      practices are clearly at greater risk today if they fail to do so in light of the
      publication of the OIG's final plan.

PMID- 16906173
TI  - Effectiveness of lumbar facet joint nerve blocks in chronic low back pain: a
      randomized clinical trial.
AB  - This randomized clinical trial was designed to determine the effectiveness of
      therapeutic lumbar facet joint nerve blocks. Two hundred patients were evaluated
      with controlled diagnostic blocks for the presence of facet joint mediated pain.
      Eighty four patients, or 42% were determined to have lumbar facet joint mediated
      pain. These patients were randomly allocated into two groups: Group I receiving
      therapeutic injections with local anesthetic and Sarapin, and Group II receiving
      therapeutic injections with a mixture of local anesthetic, Sarapin, and methyl
      prednisolone. A total of 73 patients were treated with medial branch blocks under
      fluoroscopy. Results showed that patients underwent multiple procedures over a
      period of 2(1/2) years. The mean number of procedures or interventions was 2.5 +/
      0.09 from 1 to 3 months, whereas it was 4 +/- 0.13 for 4 to 6 months, 6.1 +/-
      0.21 for 7 to 12 months, and 8.4 +/- 0.31 for 13 to 32 months. Cumulative
      significant relief with one to three injections was 100% up to 1 to 3 months, 82%
      for 4 to 6 months, 21% for 7 to 12 months, and 10% after 12 months, with a mean
      relief of 6.5 +/- 0.76 months. There was significant improvement noted in overall
      health status with improvement not only in pain relief, but also with physical,
      functional, and psychological status, as well as return-to-work status. In
      conclusion, the results of this study demonstrate that medial branch blocks with
      local anesthetic and Sarapin, with or without steroids, are a cost effective
      modality of treatment, resulting in improvement in pain status, physical status,
      psychological status, functional status and return to work.

PMID- 16906175
TI  - Imagine.

PMID- 16906176
TI  - An unusual case of shoulder pain.
AB  - Shoulder pain is a common musculoskeletal ailment. The process of determining the
      etiology of shoulder pain can be difficult. The differential diagnoses include:
      both intracapsular and extracapsular lesions; and neurologic, vascular, postural,
      and visceral causes. We present an unusual case of shoulder pain accompanied by
      loss of shoulder range of motion (ROM), initially thought to be caused by an
      intrinsic shoulder disorder. However, it ultimately was determined that a
      cervical radicular disorder caused both the impaired ROM and the patient's
      shoulder pain.

PMID- 16906177
TI  - The effect of neuraxial steroids on weight and bone mass density: a prospective
      evaluation.
AB  - The deleterious effects of corticosteroids utilized in neural blockade are a
      commonly discussed and contentious issue. Corticosteroids are considered to have
      widespread effects on almost all body systems, with suppression of the release of
      corticotropin (ACTH) from the pituitary suppressing the secretion of endogenous
      corticosteroids, thus producing a secondary adrenocortical insufficiency. Even
      though a multitude of complications of neuraxial steroids have been popularized,
      the more practical complications of corticosteroid administration are twofold -
      those resulting from withdrawal and those resulting from continued use of large
      doses. These mainly include suppression of the pituitary-adrenal axis, weight
      gain, osteopenia, osteoporosis, and a variety of other minor complications. This
      prospective evaluation was undertaken to evaluate the effect of corticosteroids
      and the dose relationship on weight gain, bone-mass density (BMD), and other
      deleterious effects of steroids. The study population consisted of 204 patients;
      however, complete data were available on only 123 patients. These patients were
      divided into two groups, with group I receiving neural blockade without any
      steroids, and, Group II consisting of patients receiving neuraxial steroids. The
      results of serial determination of weight and BMD showed no significant change at
      any interval or at the end of 1 year in all 123 patients with or without steroid
      administration. In addition, this study also showed some improvement in BMD, as
      well as weight reduction indicating improvement in functional status. It is
      concluded that low-dose administration of neuraxial steroids is safe in patients
      suffering with chronic pain who have failed to respond to conservative modalities
      of treatment with a favorable risk-benefit ratio. This study also showed no
      deleterious effect on weight or BMD.

PMID- 16906178
TI  - Intradiscal electrothermal therapy: a preliminary report.
AB  - Internal disc disruption is a common cause of disabling low back pain in a
      substantial number of young, healthy adults. A clinical diagnosis of internal
      disruption, in absence of objective clinical findings, is convincingly
      established only by means of provocation discography. Intradiscal electrothermal
      therapy has been shown to be effective in managing chronic disabling discogenic
      pain. This prospective pilot outcome study was designed to investigate the
      effectiveness of intradiscal electrothermal annuloplasty in a series of patients
      with chronic functionally disabling discogenic low back pain. The results showed
      greater than 50% pain relief in 67% of the patients. In addition, a significant
      decrease in visual analog pain scores was also seen. Further, the assessment of
      functional status showed significant improvement with standing and walking,
      whereas sitting also demonstrated significant improvement in 62% of the patients,
      though it was not statistically significant. No complications were noted in the
      perioperative period or during the follow-up period. In conclusion, intradiscal
      electrothermal therapy is a safe and effective procedure in patients suffering
      with chronic functionally limiting discogenic pain who fail to respond to
      aggressive conservative modalities of treatments as well as interventional
      therapy with injections.

PMID- 16906179
TI  - Transforaminal lumbar epidural steroid injections.
AB  - Low back pain is an important medical, social, and economic problem involving
      approximately 15% to 39% of the population. Of the numerous therapeutic
      interventions available for treatment of chronic low back pain, including
      surgery, epidural administration of corticosteroids is one such intervention
      commonly used. Several approaches available to access the lumbar epidural space
      are the caudal, interlaminar, and transforaminal, also known as nerve root or
      selective epidural injection. The objective of an epidural steroid injection is
      to deliver corticosteroid close to the site of pathology, presumably onto an
      inflamed nerve root. This objective can be achieved by the transforaminal route
      rather than the caudal or interlaminar routes. Reports of the effectiveness of
      epidural corticosteroids have varied from 18% to 90%. However, reports of the
      effectiveness of transforaminal epidural steroids have shown it to be superior,
      with outcome data indicating cost effectiveness as well as safety. This review
      describes various aspects of transforaminal epidural steroid injections in
      managing chronic low back pain.

PMID- 16906180
TI  - HIPAA update: standards for health care electronic transactions finalized.
AB  - The Department for Health and Human Services (HHS) has issued the final rule that
      will govern electronic exchanges of financial and administrative information in
      the health care industry. About 400 different formats currently exist for
      electronic health care claims. Once compliance with this rule is required
      (October 2002 for most health care entities to which the rule applies), a
      physician will be able to submit an electronic claim in the standard transaction
      format to virtually any health plan in the United States and the health plan will
      have to accept it. Under the rule, an electronic transaction involves information
      exchanges between two parties to carry out financial or administrative activities
      related to health care. Thus, health plans will be able to pay physicians,
      authorize services, certify referrals, and coordinate benefits using a standard
      electronic format for each transaction. Conflicting state laws will be superseded
      by the standards, although HHS is developing an exception process pursuant to
      HIPAA. HIPAA required HHS to adopt data and format standards, if possible, that
      were developed by private sector standards development organizations accredited
      by the American National Standards Institute (ANSI). When conducting a
      transaction covered by the rule, physicians are required to use applicable
      medical data code sets as specified in the implementation specification that is
      valid at the time the health care is furnished. Local and proprietary codes
      currently used by health plans can no longer be used in electronic transactions
      governed by the rule after the compliance date (October 16, 2002, except for
      small health plans, which have until October 16, 2003). This summary of the
      Standards for Electronic Transactions should not be construed as legal advice or
      an opinion on specific situations. Please consult an attorney concerning your
      compliance with HIPAA and the regulations promulgated thereunder.

PMID- 16906181
TI  - Recent developments in evaluation and management services.
AB  - Evaluation and management services are important aspects of interventional pain
      management; however, significant confusion continues as to proper coding and
      documentation in this field. In addition, recent developments in the area of
      evaluation and management services over the last few months are of significance
      to interventional pain physicians. Two major developments in the year 2000
      include a warning from the Health Care Financing Administration (HCFA) with
      regards to misused codes, and issue of new draft evaluation and management
      guidelines to improve physician acceptance by simplification. The HCFA has sent
      letters to all physicians in the United States on June 1, 2000, with information
      that it will be focusing this year on two current procedural terminology (CPT)
      codes used to report evaluation and management services - 99214 and 99233. The
      HCFA contends that these codes accounted for a significant portion of coding
      errors in the last two audits and that documentation for many of these services
      was found to be sufficient only to support services more appropriately described
      by CPT codes 99212 and 99231 resulting in downcoding by two levels by HCFA and
      implying that physicians are upcoding by two levels. The second issue relates to
      the release of yet another version of the new draft evaluation and management
      guidelines by HCFA in June 2000. These were preceded by an article by the
      administrator of HCFA, Nancy-Ann Min DeParle, which was published in JAMA. The
      new guidelines are purported to eliminate "bullets" and "shading"; reduce the
      need for counting the "elements"; introduce the first specialty-specific
      vignettes; and include a nationwide study of the new proposed guidelines.

PMID- 16906182
TI  - Current issues in billing and coding in interventional pain medicine.
AB  - Interventional pain management is a dynamic field with changes occurring on a
      daily basis, not only with technology but also with regulations that have a
      substantial financial impact on practices. Regulations are imposed not only by
      the federal government and other regulatory agencies, and also by a multitude of
      other payors, state governments and medical boards. Documentation of medical
      necessity with coding that correlates with multiple components of the patient's
      medical record, operative report, and billing statement is extremely important.
      Numerous changes which have occurred in the practice of interventional pain
      management in the new millennium continue to impact the financial viability of
      interventional pain practices along with patient access to these services. Thus,
      while complying with regulations of billing, coding and proper, effective, and
      ethical practice of pain management, it is also essential for physicians to
      understand financial aspects and the impact of various practice patterns. This
      article provides guidelines which are meant to provide practical considerations
      for billing and coding of interventional techniques in the management of chronic
      pain based on the current state of the art and science of interventional pain
      management. Hence, these guidelines do not constitute inflexible treatment,
      coding, billing or documentation recommendations. It is expected that a provider
      will establish a plan of care on a case-by-case basis taking into account an
      individual patient's medical condition, personal needs, and preferences, along
      with physician's experience and in a similar manner, billing and coding practices
      will be developed. Based on an individual patient's needs, treatment, billing and
      coding, different from what is outlined here is not only warranted but essential.

PMID- 16906183
TI  - State of interventional pain medicine.

PMID- 16906184
TI  - Evolution of epidural lysis of adhesions.
AB  - Epidural neuroplasty (lysis of epidural adhesions) is an interventional technique
      that has emerged over the last 10 years as part of a multidisciplinary approach
      to treating radiculopathy with low back pain when conservative management has
      failed. Neuroplasty was at one time performed as a single-catheter technique
      using the caudal approach. It now has many variations, including placement of the
      catheter tip in the anterior epidural space. This article will discuss the
      evolution and refinement of epidural neuroplasty at our institution.

PMID- 16906185
TI  - Precision diagnostic disc injections.
AB  - Spinal pain is an important public health problem affecting the population
      indiscriminately. The structures responsible for pain in the spine include the
      vertebrae, intervertebral discs, spinal cord, nerve roots, facet joints,
      ligaments, muscles, atlanto-occipital joints, atlanto-axial joints, and
      sacroiliac joints. Even though disc herniation, facet joints, strained muscles,
      and torn ligaments have been attributed to be the cause of most spinal pain,
      either in the neck and upper extremities, upper and mid back, or low back and
      lower extremities, disorders of the disc other than disc herniation have been
      implicated more frequently than any other disorders. Once stifled by
      misinformation, discography now has applications in a number of clinical
      settings. While cervical and lumbar discography is well studied and well known,
      thoracic discography is in its nascent stages of clinical application. The value
      of discography lies in its ability to produce pain and thereby identify a "pain
      generator." This allows treatment to be based on the specific cause of pain. The
      three primary components of diagnostic disc injection are: provocation/analgesia,
      discometry, and nucleography. Despite the recent exponential growth of
      noninvasive spinal technology, diagnostic disc injection remains the sole direct
      method for definitively determining whether a disc is a physiological pain
      generator. It is clear that discography is a safe and powerful complement to the
      overall clinical context.

PMID- 16906186
TI  - The management of the atlanto-occipital and atlanto-axial joint pain.
AB  - Headaches secondary to atlanto-occipital and atlanto-axial joints are often
      associated with suboccipital pain and aggravated by lateral rotation of the
      cervical spine and/or flexion or extension of the cervical spine. They are
      frequently under-diagnosed using traditional radiological evaluation including
      plain X-rays, computerized tomographic scan, and magnetic resonance imaging.
      While the natural history of most acute atlanto-occipital and atlanto-axial joint
      inflammation is resolution over a 2-to-4-week period with conservative
      management, however, when chronicity sets in, resolution is difficult to achieve
      using conservative measures, and interventional pain management procedures may be
      indicated. This review will describe the anatomy of the upper cervical spine,
      clinical presentation of atlanto-occipital and atlanto-axial joint involvement,
      and various modalities of treatment, including conservative and interventional
      modalities.

PMID- 16906187
TI  - Cervical sympathetic and stellate ganglion blocks.
AB  - Sympathetic blocks in the cervical and upper thoracic region are commonly used
      techniques for a variety of diagnostic, therapeutic and prognostic purposes.
      Stellate ganglion block is the common nomenclature utilized, however, stellate
      ganglion is present in only 80% of the population, thus, either lower cervical
      sympathetic block or upper thoracic sympathetic block is an appropriate term. The
      cervical sympathetic ganglia are identified as the superior, middle, intermediate
      and the inferior cervical sympathetic ganglion. The superior cervical ganglia are
      approximately 3 to 5 cm in length and situated on the longus capitus muscle
      anterior to the transverse process of the second, third, and rarely the fourth
      cervical vertebrae; the middle cervical ganglia are the smallest of the cervical
      ganglia situated on the longus colli muscle, anterior to the base of the
      transverse process of the sixth vertebrae; and the intermediate cervical ganglia
      which are more consistent in position and are located on the medial side of the
      vertebral artery. The inferior cervical ganglia, when present, are located on the
      transverse process of the C7 vertebrae, whereas the first thoracic ganglia are
      situated in front of the neck of the first rib. In 70% to 80% of the population
      they are fused together forming the stellate ganglion. Stellate ganglion block or
      lower cervical sympathetic block has been advocated for both diagnostic,
      therapeutic, and prognostic purposes for a variety of conditions. Even though
      multiple techniques are advocated in performing this block, fluoroscopically
      guided sympathetic blocks are more appropriate. Complications of stellate
      ganglion block include complications related to the technique, infection, and
      pharmacological complications related to the drugs utilized. Cervical sympathetic
      or stellate ganglion block is a very commonly performed procedure. If performed
      correctly, this can provide good therapeutic, prognostic, and diagnostic values.

PMID- 16906188
TI  - Caudal epidural steroid injections.
AB  - The caudal approach to the epidural space was first reported in 1901. Injection
      of steroids to treat low back pain was introduced in 1952. Caudal epidural
      steroid injection is a safe, effective technique when performed with appropriate
      care under fluoroscopic visualization. Caudal epidural injections are associated
      with inaccurate needle placement when performed blindly in a substantial number
      of patients, resulting in intravascular injections as well as other
      complications. This review will discuss anatomic and technical considerations of
      caudal epidural injections, along with advantages, disadvantages, complications,
      and indications.

PMID- 16906189
TI  - Correct coding in interventional pain management.
AB  - The National Correct Coding Council (NCCC) was created by the Health Care
      Financing Administration (HCFA) in 1996 to help ensure that providers across
      various jurisdictions receive like payment for the same services, use the same
      codes and provide similar documentation for services performed. The Correct
      Coding Initiative (CCI) was a direct outgrowth of the NCCC's, the purpose of
      which was to identify and isolate inappropriate coding, unbundling, and other
      irregularities in coding. To avoid inappropriate or incorrect coding and billing
      in interventional pain management, it is imperative that interventional pain
      physicians and their staff be familiar with correct coding policies, as well as
      understand the meaning of Current Procedural Terminology, along with
      comprehensive codes, component codes, and mutually exclusive codes. This review
      describes CCI and various correct coding policies specifically relevant to
      interventional pain medicine. In addition, certain commonly used codes of
      interventional techniques are also described with implications of comprehensive,
      component, and mutually exclusive coding terminology.

PMID- 16906190
TI  - Evaluation and management service in interventional pain practice: doing it
      right!
AB  - Proper coding and documentation for evaluation and management services
      continuously and progressively are becoming not only complicated, but also
      confusing. Although medical evaluation of patients has been a fact of life since
      the beginnings of medical history, medicine has been substantially influenced by
      federal regulations since the enactment of Medicare. Physicians' fear of being
      prosecuted is increasing. This is reinforced by actions of the federal government
      in multiple cases with sky-high penalties and by the Office of the Inspector
      General's target of 600,000 physicians in practice in its work plan for the new
      millennium. Evaluation and management services utilization, medical necessity,
      and appropriate documentation for level and complexity of service are extremely
      important components of evaluation and management services. Similarly,
      differentiating between a consult versus a visit is also crucial to avoid
      upcoding, or in a worst-case scenario, downcoding. While the history is the same
      for all types of visits except for the complexity for each level, four types of
      physical examination are available, either in a general multisystem examination
      or a single-system examination. However, the complexity of medical decision
      making is the essential factor in deciding to which level the evaluation and
      management belong. This review will discuss various aspects of evaluation and
      management guidelines in interventional practice and also guide the physician in
      performing these evaluations in an appropriate manner with proper documentation,
      thus avoiding the pitfalls of fraud and abuse.

PMID- 16906192
TI  - Compassion and progress.

PMID- 16906191
TI  - Managed care under fire.
AB  - A recent flurry of activity in terms of litigation and legislation involving the
      managed care industry has produced mixed results. Common trends among actions
      include delayed or diminished payment and network termination, breach of
      fiduciary duty, negligence in plan administration, breach of contract and fraud,
      and prompt pay among physician cases, among plan member cases, and among
      regulatory enforcement cases. The results indicate that physicians face an uphill
      battle in their efforts to sue managed care organizations for financial causes,
      although they generally fare better if state regulators adopt their cause; plan
      members are somewhat more successful than providers, particularly in situations
      where an alleged denial of care results in injury; by far, the most successful
      litigant against managed care has been state enforcement agencies, as the states
      have been particularly successful in actions enforcing their prompt payment
      regulations. However, the managed care industry has done well in warding off
      suits against plan members under the Employee Retirement Income Security Act's
      pre-emption provisions. Despite the somewhat varying degree of success, it
      appears that there is a perception among managed care enrollees, providers of
      care, and state and federal regulators and legislators that the managed care
      industry is wrongfully enhancing its bottom line at the expense of members'
      health.

PMID- 16906193
TI  - Interventional Pain Physician: What's in a name?

PMID- 16906194
TI  - Internal disc disruption and low back pain.
AB  - Internal disc disruption is a common cause of disabling low back pain in a
      substantial number of young, healthy adults. Crock described this painful entity
      and reported annular fissures that distort the internal architecture of the disc;
      Externally the disc appears relatively intact and undeformed. A clinical
      diagnosis of internal disc disruption, in absence of objective clinical findings,
      is extremely difficult. The only convincing means to establish the diagnosis is
      provocation discography. Unfortunately, this procedure is controversial, making
      the existence of internal disc disruption suspect. Recent studies indicate the
      existence of a biochemical/ biomechanical model of discogenic pain, which
      explains the disabling low back pain in some subjects with no objective evidence
      of nerve-root compromise. However, a reluctance to acknowledge internal disc
      disruption as a valid clinical entity delays diagnosis and treatment. Failure to
      identify and treat this entity early and aggressively results in longterm
      disability, thereby perpetuating the enigma of chronic low back pain.

PMID- 16906195
TI  - The inability of the clinical picture to characterize pain from facet joints.
AB  - Facet joints, as a source of low back pain, have attracted considerable attention
      and been a source of controversy in recent years. Significant progress has been
      made in precision diagnosis of chronic low back pain with neural blockade. In the
      face of less than optimal diagnostic information offered by imaging and
      neurophysiologic studies, and in the face of mounting evidence showing lack of
      correlation between clinical features, physical findings, and diagnosis of facet
      joint mediated pain, controversial features have been described to validate the
      assumption of facet joint mediated pain by set criteria. The prevalence of lumbar
      facet joint mediated pain in patients with chronic low back pain has been
      established in this study as 42% using controlled comparative local anesthetic
      diagnostic blocks, with a false positive rate of 37%. The evaluation of role of
      various clinical features described in the literature, six features showed
      negative correlation with facet joint mediated pain. However, these six feature
      involved only a small number of patients. In conclusion, facet joint mediated
      pain is a common entity in patients suffering with chronic low back pain
      nonresponsive to conservative care, who present to a nonuniversity pain
      management practice. However, the history, clinical features, and radiological
      features are of no significance or assistance in making the diagnosis of facet
      joint mediated pain with certainty.

PMID- 16906196
TI  - Epidemiology of low back pain.
AB  - Low back pain is a symptom that cannot be validated by an external standard. It
      is a disorder with many possible etiologies, occurring in many groups of the
      population, and with many definitions. Low back pain is a common problem, with a
      prevalence in the United States ranging from 8% to 56%. It is estimated that 28%
      experience disabling low back pain sometime during their lives, 14% experience
      episodes lasting at least 2 weeks, 8% of the entire working population will be
      disabled in any given year, and the lifetime prevalence of low back pain is 65%
      to 80%. It is believed that most episodes of low back pain will be short-lived
      and that 80% to 90% of attacks of low back pain resolve in about 6 weeks,
      irrespective of the administration or type of treatment. However, multiple
      studies in the late 90s showed recurrent or chronic low back pain, evaluated at 3
      months, 6 months, or 12 months, ranging from 35% to 79%. Risk factors of low back
      pain are multifactorial, with many possible etiologies. Multiple risk factors of
      low back pain and lower-extremity pain include physical factors, social
      demographic characteristics, habits, and psychosocial factors. This review will
      discuss the epidemiology of low back pain, with emphasis on frequency, causes,
      and consequences of low back pain; the influence of age, gender, morphologic
      characteristics, and genetics; and the influence of occupational, mechanical,
      social, habitual, and psychological factors.

PMID- 16906197
TI  - A retrospective analysis of spinal canal endoscopy and laminectomy outcomes data.
AB  - Disability from back pain has continued to increase at a steady pace since the
      1950's. While no study has associated chronic disability with physical factors,
      numerous studies have correlated chronic disability with psychological factors
      and surgical intervention. Even though most common surgical interventions for
      spinal pain pertain to the herniated disc, numerous studies have indicated that
      only 1% of severe episodes of low back pain is attributable to herniated discs.
      With the advent of spinal canal endoscopy, an additional option is available for
      medical management of disc disease, which facilitates irrigation, dilution, and
      removal of inflammatory mediators, thus decreasing the chance of reactivity to
      chemical and biological mediators, and facilitating administration of
      corticosteroid medication with specificity to site of action. This pilot study
      included two groups of patients, Group 1 with 22 patients treated via spinal
      endoscopy and Group 2 with 13 patients treated via laminectomy. After spinal
      canal endoscopy, only 31.8% of Group 1 patients were continued on opioid
      medication, whereas, 92.3% of Group 2 patients were continued on opioid
      medication after laminectomy. In addition, 72% from spinal canal endoscopy group
      and only 28% from laminectomy group returned to work. In conclusion, this study
      suggested remarkable differences in outcomes when comparing patients who
      underwent spinal canal endoscopy to a similar population who underwent lumbar
      laminectomy.

PMID- 16906198
TI  - Headache management in an interventional pain practice.
AB  - More than 20 million people in the United States suffer from severe headaches.
      Most have been diagnosed as "migraines," which have been assumed to be an
      intracranial process. Recognition of the extracranial sources of headaches (such
      as supraorbital neuralgia, infraorbital neuralgia, auriculotemporal neuralgia,
      facial neuralgia, posterior auricular neuralgia, occipital neuralgia, cervical
      facet pathology, masseter spasm, sternocleidomastoid muscle spasm, trapezius
      spasm, and interspinous ligament pathology) has led to an expansion of the
      treatment options available for practitioners skilled in interventional pain
      procedures. However, unless the clinical presentation is recognized, treatment
      cannot be offered. Clinical presentation, diagnostic injections, differential
      diagnosis, and advanced neurolytic techniques are discussed in this article.

PMID- 16906199
TI  - Impairment evaluation in pain management: physician, or attorney in white coat?
AB  - Impairment and disability evaluations have become a growth industry in the United
      States. Impairment evaluation is sometimes termed independent medical evaluation,
      or IME. So-called independent medical experts are hired guns to provide opposite
      opinions, similar to attorneys in this case. IME is the practice of medicine on
      one hand. On the other hand, it is the practice of law in white coats. Impairment
      is defined as the loss of a physiologic function or of an anatomic structure.
      Disability, however, is defined as an inability or altered ability to
      successfully accomplish a given task. For successful implementation of various
      disability systems, the essential medical/legal interface can be successfully
      achieved only if the physician has at least a minimum level of understanding of
      the legal system, and the attorney has an adequate understanding of the medical
      facts and the limits of medical science. Many physicians approach impairment
      ratings and disability evaluations by extrapolating from the knowledge and
      experience gained in their specialties. However, there are numerous fundamental
      differences between the standard medical evaluation and impairment/disability
      evaluation. Important aspects of impairment evaluation include medical
      evaluation, analysis of findings, and comparison of the results. In impairment
      evaluation, it is crucial to establish causal relationship and decide on maximum
      medical improvement, apart from providing the impairment rating. This review will
      discuss various aspects of impairment evaluation.

PMID- 16906200
TI  - Appropriate documentation, billing and coding in interventional pain practice.
AB  - Appropriate documentation, billing and coding in interventional pain practice is
      a crucial issue with a wide arena of regulatory reforms. There have been reports
      of billions of dollars in losses in health care fraud. Office of Inspector
      General reports a massive war on health fraud. Substantial savings from
      prepayment audits for Part B in 1999, and continued criminal filings by the
      Department of Justice indicate persistence of Health Care Financing
      Administration to combat fraud. In addition President Clinton's initiatives to
      fight Medicare waste, fraud, and abuse have created increased fear of
      investigation or prosecution among physicians, leading to changes in their
      practice patterns. Documentation of medical necessity with coding that correlates
      with multiple components of the patient's medical record, operative report, and
      billing statement is important. This review describes the regulatory issues,
      steps in documentation of medical necessity, appropriate billing and coding, and
      examples of codes describing CPT 1999 and 2000 for a multitude of procedures.
      These illustrations and the information provide practical considerations for the
      use of interventional techniques in the management of chronic pain based on the
      current state of the art and science of interventional pain management, rules and
      regulations. However, this article and its descriptions do not constitute legal
      advice.

PMID- 16906201
TI  - OIG to issue compliance guidelines for physicians.
AB  - Interventional physicians, like many other small physician practices, are bracing
      for a soon-to-be released document from the Office of the Inspector General (OIG)
      for the Department of Health and Human Services that will provide guidance to
      physician practices interested in developing compliance programs for their
      practices. The purpose of these compliance programs is to demonstrate to
      government authorities that a provider has made an institutional commitment to
      adhere to all relevant laws as a matter of everyday practice, and may establish a
      strong basis for minimizing any penalties if a violation actually occurs. Even
      though these guidances issued by OIG are non-binding, they are particularly
      useful as they reflect the OIG's position on a wide range of compliance issues
      directly impacting physician practices. Physician compliance documents should
      include the elements that OIG believes are crucial for an effective plan
      including: written compliance policies and procedures, compliance
      officer/compliance committee, effective training and education, effective lines
      of communication, disciplinary protocols to enforce the plan, monitoring and
      auditing of the plan/program, and responsiveness to detected offenses and the
      development of corrective action plans.

PMID- 16906202
TI  - Comparison of Thoracic versus Lumbar Gray Ramus Communicans Nerve Block in the
      treatment of painful osteoporotic vertebral compression fracture.

PMID- 16906203
TI  - Interventional pain medicine in the new millennium.

PMID- 16906204
TI  - Dr. No - managed care: clinical guidelines.

PMID- 16906205
TI  - Interventional techniques in the management of chronic pain: Part 1.0.
AB  - The practice guidelines for interventional techniques in the management of
      chronic pain are systematically developed statements to assist practitioner and
      patient decisions about appropriate health care related to chronic pain. These
      guidelines are professionally derived recommendations for practices in the
      diagnosis and treatment of chronic or persistent pain. They were developed
      utilizing a combination of evidence and consensus to improve quality of care,
      increase patient access,improve patient outcomes, improve appropriateness of
      care, improve efficiency and effectiveness, and achieve cost containment.
      Included in the guidelines is a discussion of their purpose,rationale,
      importance, and methodology, and patient population, pathophysiologic basis, and
      various interventional techniques utilized in the management of chronic pain
      including rationale, outcomes, and cost effectiveness. They also describe the
      role of diagnostic blocks and therapeutic blocks with suggested algorithms for
      interventional techniques in the management of conservative care of chronic pain.

PMID- 16906206
TI  - Laser-assisted percutaneous endoscopic neurolysis.
AB  - Endoscopic lysis of adhesive scar utilizing a steerable fiberoptic scope is
      currently being performed by a growing number of physicians. Various techniques
      and medications are presently being used to lyse epidural adhesions as a way of
      improving refractory lumbar radiculopathies. We present a case report discussing
      laser-assisted endoscopic lysis with radiographic images before and after laser
      assisted neurolysis. We were able to demonstrate improvement in the filling of
      the nerve root with epidural contrast after the laser lysis of scar. This
      correlated with improvement in pain without neurologic deficit. The laser may
      represent a useful adjunct in the treatment of pain due to epidural fibrosis.

PMID- 16906207
TI  - Percutaneous lysis of epidural adhesions.
AB  - Percutaneous epidural adhesiolysis, lysis of epidural adhesions, percutaneous
      neuroplasty, or epidural neurolysis is an interventional pain management
      technique which emerged during the latter part of the 1980s. It is becoming
      established as a common treatment modality in managing chronic low back pain that
      is nonresponsive to other modalities of treatment. While epidural adhesions most
      commonly result following surgical intervention of the spine, leakage of disc
      material into the epidural space following an annular tear, or an inflammatory
      response can also result in the formation of epidural adhesions. Even though
      advanced technology, including computerized tomography and magnetic resonance
      imaging, have made significant advances in the diagnosis of epidural fibrosis, it
      is believed that epidural adhesions are best diagnosed by performing an
      epidurogram. Percutaneous lysis of epidural scar tissue, followed by the
      injection of hypertonic saline neurolysis, has been shown to be cost effective in
      multiple studies. This review discusses various aspects of percutaneous
      nonendoscopic adhesiolysis and hypertonic saline neurolysis including clinical
      effectiveness, complications, rationale, and indications.

PMID- 16906208
TI  - Why not relief?
AB  - The field of pain management is currently a battleground on several fronts with
      controversies virtually at every aspect of the subject with lack of education and
      misconception at the center of the fight. It has been shown that number of
      patients suffering with psychosomatic chronic pain are 2% or less. Similarly, it
      was also shown that the risk of true addiction in chronic pain patients was
      approximately 0.3%. Accurate anatomical diagnosis can be provided in only 15% of
      the patients utilizing traditional medical technology. The question of, "Why not
      relief?" should be raised in our society on a daily basis. It is imperative to
      understand the true nature of pain by separating the myth of psychological pain
      from the reality of organic pain and manage it appropriately utilizing all
      available means, not only narcotics and interventional technology, but also
      behavioral therapy.

PMID- 16906209
TI  - CPT 2000: interventional pain management coding in the new millennium.
AB  - Current Procedural Terminology is a systematic listing and coding of procedures
      and services performed by physicians and other providers. The CPT is the most
      widely accepted nomenclature for the reporting of procedures by physicians and
      other providers for health-care services provided by the government, and private
      health-insurance programs. It is most widely accepted for claim processing, and
      for the development of guidelines for medical care review, and it provides the
      uniform language applicable to medical education, research, and utilization. The
      CPT 2000 includes a multitude of changes. Those of most important interest to
      interventional pain management specialists include neural blockade where the
      codes used in pain management have been totally revamped. The entire section of
      neural blockade codes has been substantially altered, either by deletion,
      modification, or addition of a new code. Various deleted codes include 62274 to
      62279, 62288, 62289, 62298, and 64440 to 64445. The definitions for CPT codes
      62273, 62280, 62281, 62282, 62287, 62291, 62350, 64622, 64623, and 72285 have
      been modified and changed. Multiple new codes not only include replacement codes
      for epidurals, but also creation of codes for sacroiliac-joint injection,
      sacroiliac-joint arthrography, percutaneous lysis of epidural adhesions, facet
      joint injections at the cervical and thoracic levels, neurolytic facet-joint
      neural blockade for cervical and thoracic levels, transforaminal injection codes
      for cervical/thoracic and lumbar/sacral, epidurography and radiological
      examination. The several advantages and disadvantages of new codes and future
      directions in CPT coding are described. KEYWORDS: Interventional pain management,
      CPT 1999, CPT 2000, epidural injections, facet-joint.

PMID- 16906210
TI  - Strategic planning for pain practice growth.
AB  - Strategy formation involves understanding the environment and strengths and
      weaknesses of a practice to develop a game plan to achieve goals. It starts with
      the creation of a mission statement that defines a long-term vision of what the
      practice seeks to be and the markets it seeks to serve. Once the mission of the
      practice is understood, the target markets and competition must be analyzed prior
      to defining the goals. Once a strategic plan is developed, communication with all
      employees is crucial. Everything that the practice does should be in support of
      the strategic plan and in pursuit of obtaining the goals contained within. Once
      created, the strategic plan is the foundation of the practice and should only be
      changed for compelling reasons such as a competitive threat, environmental
      changes, or trends in purchasing behavior. Reviewing the strategic plan once a
      year, making periodic reappraisals and fine-tuning adjustments as the environment
      changes is crucial. This helps ensure that the practice avoids complacency and
      affirms that it is in the right business and achieving the desired results.

PMID- 16906212
TI  - Letter from the editor.

PMID- 16906211
TI  - Letter from the executive director.

PMID- 16906213
TI  - The role of evaluation and management services in pain management.
AB  - Evaluation and management services are an integral part of interventional pain
      management. Health Care Financing Administration "HCFA" and American Medical
      Association "AMA" promulgate rules and regulations in the evaluation and
      management arena. Proper understanding and appropriate coding is a crucial part
      of interventional pain management, as consequences of inappropriate coding and
      insufficient documentation to support charges billed to Medicare include not only
      civil monetary penalties, but exclusion from Medicare program and prison terms.
      Medical record documentation is required to record pertinent facts, findings, and
      observations about an individual's health history including the past and present
      illnesses, examinations, tests, treatments, and outcomes. In essence, proper
      medical record documentation must provide the information and answer the
      questions including why?, what?, where?, and when?. Descriptors for the levels of
      evaluation and management services recognize seven components which include
      history, physical examination, medical decision making, counseling, coordination
      or care, nature of the presenting problem, and time spent. Based on the type of
      history, physical examination, complexity of medical decision making, patient
      evaluation services are of several types, which include problem focused, expanded
      problem focused, detailed, comprehensive with moderate complexity, and
      comprehensive with high complexity. History includes chief complaint; history of
      present illness; review of systems; and past, family, and/or social history.
      Similar to the history, physical examination also encompasses four types, which
      include a problem focused examination, an expanded-problem focused examination, a
      detailed examination, and a comprehensive examination. This review describes
      evaluation and management services of new patients, as well as established
      patients with sample office evaluations.

PMID- 16906215
TI  - Corporate compliance program.

PMID- 16906214
TI  - The impact of national correct coding policy on interventional pain management.
AB  - Health Care Financing Administration ("HCFA") created the National Correct Coding
      Council ("NCCC") to help ensure that providers across various jurisdictions
      received like payment for the same services and use the same codes and provide
      similar documentation for services performed. As a direct out growth of NCCC's
      work, HCFA established the National Correct Coding Policy in 1996 and eventually
      implemented the Medicare "Correct Coding Initiative" to identify and isolate
      inappropriate coding, unbundling, and other irregularities in coding. To
      appropriately implement National Correct Coding Policy in interventional pain
      management an interventional pain management specialist and their staff must be
      familiar with correct coding policies as well as understand the physicians
      current procedural terminology (CPT, medical surgical practice and packages,
      modifiers, separate procedures, comprehensive and component services, incorrect
      coding/unbundling and various specific issues relevant to practice of
      interventional pain management) Comprehensive codes include certain defined
      services that are separately identifiable by other codes known as component
      codes. Because component codes are captured by comprehensive codes they man not
      be listed separately when the complete procedure is done. For example, in
      interventional pain management, 62279, which is continuous lumbar epidural, is
      considered a comprehensive code. Various component codes include 62270, 62272 -
      62274, 62276 - 62278, 62288 and 62289, among others. This review describes
      National Correct Coding Policy, correct procedural terminology, medical and
      surgical practice and packages, evaluation and management services along with
      description of most codes used in interventional pain management with correcting
      coding edits for comprehensive codes and for mutually exclusive codes.

PMID- 16906216
TI  - Non-endoscopic and endoscopic adhesiolysis in post-lumbar laminectomy syndrome: a
      one-year outcome study and cost effectiveness analysis.
AB  - Post lumbar laminectomy syndrome with its resultant chronic low back pain is
      estimated to occur in 20% to 50% of the patients. Among various procedures
      available, lysis of epidural adhesions is considered as one of the effective
      therapeutic modalities of management in these patients, and may be performed
      either non-endoscopically or endoscopically. This retrospective evaluation
      included 120 post lumbar laminectomy patients who underwent either non-endoscopic
      adhesiolysis (Group I) or endoscopic adhesiolysis (Group II) with 60 consecutive
      patients in each group. The quality of pain relief when greater than 50% was
      considered significant. Results showed all patients experienced significant
      relief following both procedures even though the number of patients experiencing
      significant relief decreased with both techniques over a time period. Overall
      relief with the first procedure (mean + SEM) was 12 + 3.2 weeks for Group I, and
      it was 20 + 2.9 weeks for Group II with significantly longer improvement in Group
      II than Group I. At one year follow up, the results showed that with repeat
      procedures, 72% in Group I and 40% in Group II experienced significant relief at
      6 months, whereas at 12 months, it decreased to 52% in Group I and 22% in Group
      II, with a significantly greater number of patients experiencing relief at 6
      months and 12 months in Group I, than Group II, even though Group I patients
      underwent a greater number of procedures. Cost effectiveness analysis showed
      Group I patients experiencing significant relief at a cost of $40 per week, with
      one year quality of life improvement for $2,080, whereas it was $135 per week
      improvement in Group II with a one year quality of life improvement at a cost of
      $7,020 with significant difference noted in cost effectiveness. In conclusion,
      non-endoscopic epidural adhesiolysis and administration of corticosteroids and
      hypertonic saline is a safe and cost effective procedure for relieving chronic
      intractable pain in post lumbar laminectomy patients who failed to respond to
      other modalities of treatment. Similarly, endoscopic adhesiolysis with the
      administration of corticosteroids is also a safe and possibly cost-effective
      technique for relief of chronic intractable pain failing to respond to other
      modalities of treatments.

PMID- 16906217
TI  - Prevalence of lumbar facet joint pain in chronic low back pain.
AB  - This prospective study was designed to determine the prevalence of lumbar facet
      joint pain in a consecutive series of patients with chronic low back pain treated
      at an interventional, multidisciplinary private pain management practice
      utilizing double diagnostic blocks, to determine the prevalence of false positive
      rate of uncontrolled facet joint blocks, and to determine the relationship of
      clinical features of responders and non-responders to double diagnostic blocks.
      One hundred and twenty patients with low back pain with or without lower
      extremity pain were selected. The procedure consisted of diagnostic blocks using
      lidocaine and bupivacaine on separate occasions, usually two weeks apart. Each
      facet joint nerve was infiltrated with either 0.4 to 0.6 ml of 1% lidocaine
      (Xylocaine(R)) or 1% lidocaine (Xylocaine(R)) and 0.25% bupivacaine
      (Marcaine(R)). A definite response was defined as substantial with at least 75%
      relief of pain in the symptomatic area following local anesthetic block.
      Confirmatory blocks using bupivacaine 0.25% were performed at the same levels as
      the first injection if definite relief was obtained. The response to bupivacaine
      blocks which lasted longer than the lidocaine blocks was accepted as a positive
      response. All blocks were performed under fluoroscopic guidance. Eighty-one
      patients (67.5%) reported a definite response to lidocaine blocks. Confirmatory
      blocks with bupivacaine were performed in all 81 patients with 54 patients, i.e.
      45% of total sample or 66.6% of lidocaine positive group reporting definite
      response with a false positive rate of 41%. Prevalence and relationship of pain
      referral pattern in patients with and without facet joint pain confirmed by
      double blocks showed no significant correlation. We found no relationship between
      the history, physical findings, age, gender, trauma, duration of pain, and
      diagnostic blocks. However, history of previous surgery showed a negative
      correlation as only 29% of the patients after previous surgery were positive in
      contrast to 51% of the nonsurgical population. The results of this study echo
      previous concerns of reliability of uncontrolled single blocks, history, and
      clinical features. This study demonstrated that the facet joint is a source of
      pain in 45% of the patients suffering with chronic low back pain in an
      interventional pain management setting in a private practice.

PMID- 16906218
TI  - Neural blockade in cervical pain syndromes.
AB  - Chronic neck pain, headache, and arm pain are some of the most common patient
      complaints confronting today's health care provider. Chronic neck pain is
      reported to be a frequency symptom in 34% of the general population with 14% of
      the general population reporting neck pain that lasted for more than 6 months.
      The magnitude of the problem is demonstrated by increase of cervical spine
      surgery by 45% and cervical fusion by 70% over a ten year period from 1979
      through 1988. Therapeutic effectiveness of a large variety of interventions in
      managing chronic neck pain is inconclusive. Pain and dysfunction have been
      attributed to a number of structure in the neck which have a potential for
      producing a pain pattern in the neck, head, and upper extremity which include
      intervertebral disc, nerve roots, facet joints, and ligamentous and muscular
      structures. Neural blockade in the cervical spine, though introduced in 1912,
      lagged behind that of the lumbar spine. At the present time, neural blockade is
      an extremely popular tool for diagnostic purposes in evaluation of neck pain,
      even though it has not developed a definitive role in the management of chronic
      neck pain and associated syndromes. The object of this review is to focus on
      various aspects of neural blockade in the management of chronic neck pain and
      associated syndromes including its rationale, clinical effectiveness,
      indications, and complications.

PMID- 16906219
TI  - Association of the T+294C polymorphism in PPAR delta with low HDL cholesterol and
      coronary heart disease risk in women.
AB  - BACKGROUND: The +T294C polymorphism in PPARdelta represents a functional SNP
      affecting transcriptional activity of the PPARdelta gene. To address whether this
      polymorphism is associated with the risk for coronary heart disease and/or plasma
      lipid levels in women, we studied a group of 967 female patients with
      hyperlipidaemia in the presence (n=453) or absence (n=514) of coronary heart
      disease. METHODS: 967 female patients with or without coronary heart disease were
      genotyped using mutagenically separated polymerase chain reaction (MS-PCR).
      Statistical analysis was performed according to genotype with parameters of lipid
      metabolism as dependant variables. RESULTS: A highly significant association
      between the rare C allele and lower plasma HDL concentrations was found in female
      subjects. The effect remained significant after correcting for multiparametric
      testing according to Bonferoni and was seen only in subjects with a BMI below the
      median. Moreover, a significant association of the C-allele with coronary heart
      disease and BMI was obtained. Regarding the entire group, trends towards higher
      VLDL and LDL levels were observed. CONCLUSIONS: Our data show for the first time
      that the PPARdelta +T294C polymorphism is associated with lipid levels and
      coronary heart disease in women. However, the molecular mechanism of action
      remains to be elucidated.

PMID- 16906220
TI  - In vitro bactericidal activities of Japanese rice-fluid against Helicobacter
      pylori strains.
AB  - BACKGROUND: Helicobacter pylori has now been widely recognized as a causative
      agent of gastroduodenal diseases. The development of safer anti- H. pylori
      compounds is desirable due to the antibiotic-resistant strains emerged to date.
      METHODS: We successfully developed the compounds of Rice-fluid derived from
      unpolished, polished, and usually cooked Japanese rice, and investigated their in
      vitro antibacterial activities by means of the Time-Kill-Curve methods against
      various species of bacteria including H. pylori strains. RESULTS: All of the
      compounds revealed keen bactericidal activities against H. pylori, followed by
      Streptococcus pneumoniae and Campylobacter jejuni strains, but failed to affect
      the viability of other bacterial species investigated including staphylococci,
      enterococci, Pseudomonas aeruginosa, and other gram-negative rods belonging to
      the family Enterobacteraceae. The bactericidal activities were demonstrated to be
      time- and concentration-dependent. CONCLUSIONS: The compounds of Rice-fluid are
      considered to be potentially new and safe therapeutic regimens against H. pylori
      infections. The mechanism of their bactericidal activities against H. pylori
      strains remains to be elucidated.

PMID- 16906221
TI  - Low temperature tolerance of human embryonic stem cells.
AB  - This study investigated the effects of exposing human embryonic stem cells (hESC)
      to 4 degrees C and 25 degrees C for extended durations of 24h and 48h
      respectively. Cell survivability after low temperature exposure was assessed
      through the MTT assay. The results showed that hESC survivability after exposure
      to 25 degrees C and 4 degrees C for 24h was 77.3 +/- 4.8 % and 64.4 +/- 4.4 %
      respectively (significantly different, P < 0.05). The corresponding survival
      rates after 48h exposure to 25 degrees C and 4 degrees C was 71.0 +/- 0.5 % and
      69.0 +/- 2.3 % respectively (not significantly different, P > 0.05). Spontaneous
      differentiation of hESC after low temperature exposure was assessed by
      morphological observations under bright-field and phase-contrast microscopy, and
      by immunocytochemical staining for the pluripotency markers SSEA-3 and TRA-1-81.
      hESC colonies were assigned into 3 grades according to their degree of
      spontaneous differentiation: (1) Grade A which was completely or mostly
      undifferentiated, (2) Grade B which was partially differentiated, and (3) Grade C
      which was mostly differentiated. In all low temperature exposed groups, about 95%
      of colonies remain undifferentiated (Grade A), which was not significantly
      different (P > 0.05) from the unexposed control group maintained at 37 degrees C.
      Additionally, normal karyotype was maintained in all low temperature-exposed
      groups, as assessed by fluorescence in situ hybridization (FISH) of metaphase
      spreads with telomere and centromere-specific PNA probes. Further analysis with m
      FISH showed that chromosomal translocations were absent in all experimental
      groups. Hence, hESC possess relatively high-tolerance to extended durations of
      low temperature exposure, which could have useful implications for the salvage of
      hESC culture during infrequent occurrences of incubator break-down and power
      failure.

PMID- 16906222
TI  - PARP-1 inhibitors: are they the long-sought genetically specific drugs for
      BRCA1/2-associated breast cancers?
AB  - Recent studies demonstrated that PARP-1 [poly(ADP-ribose) polymerase-1]
      inhibitors kill breast cancer associated gene-1 and -2 (BRCA1/2) deficient cells
      with extremely high efficiency while BRCA+/- and BRCA+/+ cells are relatively non
      responsive to the treatment. It was therefore proposed that PARP-1 inhibitors
      might be the long-sought genetically specific drugs that are both safe and
      effective for treating BRCA1/2-associated breast cancers. However, a report
      published in a recent issue of the International Journal of Biological Sciences
      revealed that PARP-1 inhibitors, although able to kill naive BRCA1 mutant cells
      with high specificity both in vitro and in vivo, exhibit minimal specificity in
      inhibiting the growth of mouse mammary tumor cells irrespective of their BRCA1
      status in allograft nude mice. Non-specific inhibition in human BRCA1+/+, BRCA1+/
      , and BRCA1-/- breast cancer cells by PARP-1 inhibitors was also observed.
      Additional mutations occurring during cancer progression may be a culprit,
      although the exact cause for the resistance of BRCA1-/- breast cancer cells to
      PARP-1 inhibitors remains elusive. These findings suggest that PARP inhibition
      may serve as an approach for the prevention of BRCA related breast cancer and may
      be useful in combination with other chemotherapeutic agents in the treatment of
      breast cancer.

PMID- 16906223
TI  - Role of IFN-gamma in induction of Foxp3 and conversion of CD4+ CD25- T cells to
      CD4+ Tregs.
AB  - IFN-gamma is an important Th1 proinflammatory cytokine and has a paradoxical
      effect on EAE in which disease susceptibility is unexpectedly heightened in IFN
      gamma-deficient mice. In this study, we provide what we believe is new evidence
      indicating that IFN-gamma is critically required for the conversion of CD4+ CD25-
      T cells to CD4+ Tregs during EAE. In our study, the added severity of EAE in IFN
      gamma knockout mice was directly associated with altered encephalitogenic T cell
      responses, which correlated with reduced frequency and function of CD4+ CD25+
      Foxp3+ Tregs when compared with those of WT mice. It was demonstrated in both
      human and mouse systems that in vitro IFN-gamma treatment of CD4+ CD25- T cells
      led to conversion of CD4+ Tregs as characterized by increased expression of Foxp3
      and enhanced regulatory function. Mouse CD4+ CD25- T cells, when treated in vitro
      with IFN-gamma, acquired marked regulatory properties as evidenced by suppression
      of EAE by adoptive transfer. These findings have important implications for the
      understanding of the complex role of IFN-gamma in both induction and self
      regulation of inflammatory processes.

PMID- 16906224
TI  - Dual role of transcription factor FoxO1 in controlling hepatic insulin
      sensitivity and lipid metabolism.
AB  - Hepatic insulin resistance affects both carbohydrate and lipid metabolism. It has
      been proposed that insulin controls these 2 metabolic branches through distinct
      signaling pathways. FoxO transcription factors are considered effectors of the
      pathway regulating hepatic glucose production. Here we show that adenoviral
      delivery of constitutively nuclear forkhead box O1 (FoxO1) to mouse liver results
      in steatosis arising from increased triglyceride accumulation and decreased fatty
      acid oxidation. FoxO1 gain of function paradoxically increased insulin
      sensitivity by promoting Akt phosphorylation, while FoxO1 inhibition via siRNA
      decreased it. We show that FoxO1 regulation of Akt phosphorylation does not
      require DNA binding and is associated with repression of the pseudokinase tribble
      3 (Trb3), a modulator of Akt activity. This unexpected dual role of FoxO1 in
      promoting insulin sensitivity and lipid synthesis in addition to glucose
      production has the potential to explain the peculiar admixture of insulin
      resistance and sensitivity that is commonly observed in the metabolic syndrome.

PMID- 16906226
TI  - The neurofibromin GAP-related domain rescues endothelial but not neural crest
      development in Nf1 mice.
AB  - Neurofibromatosis type I (NF1; also known as von Recklinghausen's disease) is a
      common autosomal-dominant condition primarily affecting neural crest-derived
      tissues. The disease gene, NF1, encodes neurofibromin, a protein of over 2,800
      amino acids that contains a 216-amino acid domain with Ras-GTPase-activating
      protein (Ras-GAP) activity. Potential therapies for NF1 currently in development
      and being tested in clinical trials are designed to modify NF1 Ras-GAP activity
      or target downstream effectors of Ras signaling. Mice lacking the murine homolog
      (Nf1) have mid-gestation lethal cardiovascular defects due to a requirement for
      neurofibromin in embryonic endothelium. We sought to determine whether the GAP
      activity of neurofibromin is sufficient to rescue complete loss of function or
      whether other as yet unidentified functions of neurofibromin might also exist.
      Using cre-inducible ubiquitous and tissue-specific expression, we demonstrate
      that the isolated GAP-related domain (GRD) rescued cardiovascular development in
      Nf1(-/-) embryos, but overgrowth of neural crest-derived tissues persisted,
      leading to perinatal lethality. These results suggest that neurofibromin may
      possess activities outside of the GRD that modulate neural crest homeostasis and
      that therapeutic approaches solely aimed at targeting Ras activity may not be
      sufficient to treat tumors of neural crest origin in NF1.

PMID- 16906225
TI  - Impaired clearance of apoptotic cardiocytes is linked to anti-SSA/Ro and -SSB/La
      antibodies in the pathogenesis of congenital heart block.
AB  - The role of cardiocytes in physiologic removal of apoptotic cells and the
      subsequent effect of surface binding by anti-SSA/Ro and -SSB/La antibodies was
      addressed. Initial experiments evaluated induction of apoptosis by extrinsic and
      intrinsic pathways. Nuclear injury and the translocation of SSA/Ro and SSB/La
      antigens to the fetal cardiocyte plasma membrane were common downstream events of
      Fas and TNF receptor ligation, requiring caspase activation. As assessed by phase
      contrast and confirmed by confocal microscopy, coculturing of healthy cardiocytes
      with cardiocytes rendered apoptotic via extrinsic pathways revealed a clearance
      mechanism that to our knowledge has not previously been described. Cultured fetal
      cardiocytes expressed phosphatidylserine receptors (PSRs), as did cardiac tissue
      from a fetus with congenital heart block (CHB) and an age-matched control.
      Phagocytic uptake was blocked by anti-PSR antibodies and was significantly
      inhibited following preincubation of apoptotic cardiocytes with chicken and
      murine anti-SSA/Ro and -SSB/La antibodies, with IgG from an anti-SSA/Ro- and 
      SSB/La-positive mother of a CHB child, but not with anti-HLA class I antibody. In
      a murine model, anti-Ro60 bound and inhibited uptake of apoptotic cardiocytes
      from wild-type but not Ro60-knockout mice. Our results suggest that resident
      cardiocytes participate in physiologic clearance of apoptotic cardiocytes but
      that clearance is inhibited by opsonization via maternal autoantibodies,
      resulting in accumulation of apoptotic cells, promoting inflammation and
      subsequent scarring.

PMID- 16906229
TI  - Time-resolved optical measurements with spread spectrum excitation.
AB  - We propose a novel method for measuring time-dependent optical quantities. A
      train of excitation pulses modulated by a pseudorandom bit sequence is used as
      the light source, and a cross-correlation scheme is used to retrieve the impulse
      response. Simulation results of the temporal point-spread function of a diffusive
      wave are provided, as well as experimental results of a fluorescence decay
      profile. It is demonstrated that our new time-resolved technique can lead to high
      signal-to-noise ratios and short data acquisition times. A fluorescence-time
      dependent suppression process was also been discovered.

PMID- 16906227
TI  - Allelic dilution obscures detection of a biologically significant resistance
      mutation in EGFR-amplified lung cancer.
AB  - EGFR is frequently mutated and amplified in lung adenocarcinomas sensitive to
      EGFR inhibitors gefitinib and erlotinib. A secondary mutation, T790M, has been
      associated with acquired resistance but has not been shown to be sufficient to
      render EGFR mutant/amplified lung cancers resistant to EGFR inhibitors. We
      created a model for studying acquired resistance to gefitinib by prolonged
      exposure of a gefitinib-sensitive lung carcinoma cell line (H3255; EGFR mutated
      and amplified) to gefitinib in vitro. The resulting resistant cell line acquired
      a T790M mutation in a small fraction of the amplified alleles that was undetected
      by direct sequencing and identified only by a highly sensitive HPLC-based
      technique. In gefitinib-sensitive lung cancer cells with EGFR mutations and
      amplifications, exogenous introduction of EGFR T790M effectively conferred
      resistance to gefitinib and continued ErbB-3/PI3K/Akt signaling when in cis to an
      activating mutation. Moreover, continued activation of PI3K signaling by the
      PIK3CA oncogenic mutant, p110alpha E545K, was sufficient to abrogate gefitinib
      induced apoptosis. These findings suggest that allelic dilution of biologically
      significant resistance mutations may go undetected by direct sequencing in
      cancers with amplified oncogenes and that restoration of PI3K activation via
      either a T790M mutation or other mechanisms can provide resistance to gefitinib.

PMID- 16906231
TI  - Quantifying the role of water in protein-carbohydrate interactions.
AB  - Water-mediated interactions play a key role in carbohydrate-lectin binding, where
      the interactions involve a conserved water that is separated from the bulk
      solvent and present a bridge between the side chains of the protein and the
      carbohydrate ligand. To apply quantum mechanical methods to examine the role of
      conserved waters, we present an analysis in which the relevant carbohydrate atoms
      are modeled by methanol, and in which the protein is replaced by a limited number
      of amino acid side chains. Clusters containing a conserved water and a
      representative amino acid fragment were also examined to determine the influence
      of amino acid side chains on interaction energies. To quantify the differential
      binding energies of methanol versus water, quantum mechanical calculations were
      performed at the B3LYP/6-311++G(3df,3pd)//B3LYP/6-31+G(d) level in which either a
      methanol molecule was bound to the conserved water (liganded state) or in which a
      water molecule replaces the methanol (unliganded state). Not surprisingly, the
      binding of a water to clusters containing charged amino acid side chains was more
      favorable by 1.55 to 7.23 kcal/mol than that for the binding of a water to the
      corresponding pure water clusters. In contrast, the binding energy of water to
      clusters containing polar-uncharged amino acid side chains ranged from 4.35
      kcal/mol less favorable to 4.72 kcal/mol more favorable than for binding to the
      analogous pure water clusters. The overall trend for the binding of methanol
      versus water, in any of the clusters, favored methanol by an average value of
      1.05 kcal/mol. To extend these studies to a complex between a protein
      (Concanavalin A) and its carbohydrate ligand, a cluster was examined that
      contained the side chains of three key amino acids, namely asparagine, aspartate,
      and arginine, as well as a key water molecule, arranged as in the X-ray
      diffraction structure of Con A. Again, using methanol as a model for the
      endogenous carbohydrate ligand, energies of -5.94 kcal/mol and -5.70 kcal/mol
      were obtained for the binding of methanol and water, respectively, to the Con A
      water cluster. The extent to which cooperativity enhanced the binding energies
      has been quantified in terms of nonadditive three-body contributions. In general,
      the binding of water or methanol to neutral dimers formed cooperative clusters;
      in contrast, the cooperativity in charged clusters depended on the overall
      geometry as well as the charge.

PMID- 16906230
TI  - EVALUATION OF DRUG ABUSE TREATMENT MEDICATIONS: CONCORDANCE BETWEEN CLINICAL AND
      PRECLINICAL STUDIES.

PMID- 16906232
TI  - Does the Organization of Emotional Expression Change Over Time? Facial
      Expressivity From 4 to 12 Months.
AB  - Differentiation models contend that the organization of facial expressivity
      increases during infancy. Accordingly, infants are believed to exhibit
      increasingly specific facial expressions in response to stimuli as a function of
      development. This study tested this hypothesis in a sample of 151 infants (83
      boys and 68 girls) observed in 4 situations (tickle, sour taste, arm restraint,
      and masked stranger) at 4 and 12 months of age. Three of the 4 situations showed
      evidence of increasing specificity over time. In response to tickle, the number
      of infants exhibiting joy expressions increased and the number exhibiting
      interest, surprise, and surprise blends decreased from 4 to 12 months. In tasting
      a sour substance, more infants exhibited disgust and fewer exhibited joy and
      interest expressions, and fear and surprise blends over time. For arm restraint,
      more infants exhibited anger expressions and anger blends and fewer exhibited
      interest and surprise expressions and surprise blends over time. In response to a
      masked stranger, however, no evidence of increased specificity was found.
      Overall, these findings suggest that infants increasingly exhibit particular
      expressions in response to specific stimuli during the 1st year of life. These
      data provide partial support for the hypothesis that facial expressivity becomes
      increasingly organized over time.

PMID- 16906234
TI  - [Epidemiology of peripheral arterial disease in Germany. What is evident, what
      remains unclear?].
AB  - The prevalence of the peripheral arterial disease (PAD) varies with the analysed
      population and the screening method. The prevalence of the symptomatic PAD,
      derived from questionnaires, ranges from around 1% within the 50 years-old up to
      5% within the 80 years-old. Due to the low specificity of such questionnaires
      this method has lost its relevance. In epidemiologic studies determination of the
      ankle/brachial index (ABI) is recommended for screening. ABI >0.9 indicates PAD.
      Based on the ABI the prevalence of the PAD in Germany in women aged 45-49 years
      is 2.3% and in men 2.6%. It increases to 10.4% and 15.2% in 70-75 years old women
      and men respectively. Real prevalence of PAD is assumed to be even higher,
      because ABI determination is biased to select people with more severe PAD and
      misses those with excellent collateral perfusion. Patients suffering from PAD
      with a chronic critical limb ischaemia (CLI) are characterised by the worst
      prognosis regarding limb salvage and mortality. Although the exact prevalence of
      CLI is unknown, it is assumed that CLI affects more than 2% of all PAD patients.

PMID- 16906235
TI  - [Mutation in factor II and factor V gene in patients with peripheral arterial
      occlusive disease].
AB  - Mutations in factor-V- and factor-II-genes are correlated with an increased risk
      for venous thrombosis according to the literature. The significance of the
      mutations in factor- II- and factor-V-genes for the development of the peripheral
      arterial occlusive disease is not known. Therefore, we investigated the presence
      of these mutations in 152 patients with documented peripheral arterial occlusive
      disease and 318 controls without peripheral arterial occlusive disease with
      polymerase chain reaction (PCR). There was no association between factor-II
      mutation and peripheral arterial occlusive disease. The factor-V-mutation,
      however, was increased in patients with peripheral arterial occlusive disease
      double fold (12 positive cases in 318 controls, 12 positive cases in 152 patients
      with peripheral arterial occlusive disease). The significance level was reached
      (p = 0.05) in statistical analysis but the result did not fall below the
      significance level as necessary to reach statistical significance (odds ratio
      2.19). Nevertheless, from these data we have to discuss a biological relevance of
      factor-V-mutation in the pathogenesis of peripheral arterial occlusive disease.

PMID- 16906236
TI  - [Markers predicting progression of disease in PAD: Which of them are both
      relevant to clinical practice and economically justifiable?].
AB  - The high cardiovascular morbidity and mortality on peripheral arterial disease
      (PAD) are attributable to the pronounced tendency to generalization of the
      atherosclerotic process, the systemic progression of atherosclerosis. The crucial
      objective in management of a PAD consists in preventing systemic progression. The
      prognosis can be improved by early diagnosis and early prediction of individual
      risk with subsequent risk-adapted prevention and causal therapy. Early diagnosis
      and risk prediction are measures that are already part of the repertory of the
      general practitioner. Practicable and economically justifiable parameters that
      nevertheless have a high predictive value are therefore required to stratify
      individual risk. The vascular indicators ankle-arm index and the localization of
      the PAD as well as the classical cardiovascular risk factors including
      homocysteine are suitable. Weighting of these parameters in a multivariable risk
      score enable the population with the highest risk of early generalization of
      atherosclerosis to be identified in PAD.

PMID- 16906237
TI  - [Are the TASC recommendations for diagnosis and treatment of PAOD still
      relevant?].
AB  - With regards to the rapid progress of interventional therapy in the treatment of
      PAOD the revision of the published guidelines (TASC Recommendations 2000) is more
      than necessary. The current options in therapy are modified constantly.
      Therefore, published recommendations might be not up-to-date. In consideration of
      the number of interventions and operations which are performed throughout Europe
      a trend towards less invasive treatment becomes apparent. Guidelines and
      recommendations from the Charing Cross and the ACC/AHA (ACC/AHA Guidelines for
      the Management of Patients With Peripheral Arterial Disease 2005) are reflecting
      this development. Regardless of the complexity of the planned procedure
      interventional treatment is almost always first choice therapy. A yearly revision
      of the actual guidelines would be useful, leading to an up-to-date modality.
      Although in the diagnostic pathway MRI and CTA gain more importance, the gold
      standard in diagnosis of PAOD remains the standardised measurement of the walking
      capacity, ankle-brachial index (ABI) and duplex ultrasound.

PMID- 16906238
TI  - [Systemic and regional fibrinolytic treatment of peripheral arterial occlusions:
      proven indications?].
AB  - Catheter-based treatment of intraarterial thrombus can be used successfully as a
      treatment to recanalize acutely occluded native arteries or bypasses associated
      with acute limb ischaemia. It should be used if the ischaemia not already caused
      sensory and/or paralytic disorders that require urgent open surgical treatment.
      Advantages of pursuing immediate angiography in patients with acute limb
      ischaemia include delineation of the limb arterial anatomy with visualization of
      both inflow and runoff vessels and clearing intraarterial thrombus from the
      distal runoff vessels. Thus, final treatment can be planned electively as an
      intervention of open surgery. A metaanalysis comparing lysis and surgery that
      included three randomized trials and case series concluded that lysis improved 6
      to 12 months limb salvage and reduced mortality compared with surgery. The
      transformation of an acute arterial occlusion into a chronic one is not clearly
      defined. Thus, fibrinolytic therapy can be successfully used for occlusions
      supposed to be older than six months.

PMID- 16906239
TI  - [Vasoactive agents and prostanoids in the therapy of PAD: facts, questions,
      disproven assumptions].
AB  - In the view of the AkdA (Drug Committee of the German Medical Profession), the
      efficacy in intermittent claudication is currently proven only for Naftidrofuryl,
      whereas in the opinion of the DGA (German Society of Angiology) also that of
      prostaglandin E(1) is proven. Both drugs are indicated if neither walking
      exercise nor vascular or endovascular reconstruction are feasible. In critical
      limb ischaemia (Fontaine stage III/IV), the efficacy of prostaglandin E(1) and
      iloprost is proven according to both the treatment recommendations of the DGA and
      the ACC/AHA Guidelines. The AkdA also agrees with the administration of
      prostanoids, even though it considers their efficacy not sufficiently proven in
      accordance with CPMP criteria. Here, prostaglandin E(1) is approved for the
      treatment of Fontaine's stage III/IV regardless of its etiology, whereas iloprost
      is approved only for the treatment of thrombo-angiitis obliterans.

PMID- 16906240
TI  - [Is the generally accepted therapeutic benefit of exercise training in patients
      with peripheral arterial occlusive disease evidence based? Analysis of the
      Cochrane review].
AB  - When assessing the quality of clinical trials in intermittent claudication, on
      principle the same strict biometric and medical standards need to be applied for
      studies on the effect of walking exercise as for conservative drug treatment
      studies. However, as demonstrated by a recent review of the Cochrane
      Collaboration, this is apparently not always the case. The review included ten
      randomized controlled studies published between 1966 and 1997 with a total of 258
      patients. The exercise regimes varied considerably between studies with regard to
      mode, intensity, frequency, duration and supervision, just as the treadmill tests
      employed to measure walking distance and walking time, respectively (primary
      endpoint). None of these studies used a confirmatory approach, and they all have
      a number of further methodological flaws when taking current biometric and
      medical guidelines into account. Also unmentioned in the abstract remains the
      important fact that, owing to missing data, finally only 53 patients from three
      studies could be pooled for the actual meta-analysis. All in all, the Cochrane
      review under discussion here is hardly suitable to scientifically prove the
      generally accepted efficacy of walking exercise in intermittent claudication. At
      the same time, it becomes clear that even publications of well-reputed
      institutions such as the Cochrane Collaboration should always be critically
      scrutinized. On the other hand, applying modern guidance for investigation under
      the aspect of evidence based medicine must not lead to a retrospective
      discrimination of accepted historical scientific data and thereby call into
      question proven therapeutic strategies.

PMID- 16906241
TI  - [Resistance to acetylsalicylic acid and clopidogrel: current status].
AB  - Resistance to acetylsalicylic acid (ASA) or clopidogrel is understood from the
      clinical point of view as failure of the drugs to prevent recurrent vascular
      occlusions. Non-response to ASA and clopidogrel is defined from the laboratory
      aspect as an inability to cause in vitro detectable platelet function inhibition.
      It would be beneficial to monitor non-response to ASA or clopidogrel with
      platelet function methods, which detect the specific effect of these drugs, and
      thus prevent clinical events caused by failure of therapy. Non-response to ASA
      and clopidogrel are detected with different platelet function methods, which are
      not always clinically standardized and are assessing only the global platelet
      function and not the specific drug effect. Although various studies reporting 5
      to 59% non-response for both drugs, support a clinical relevance of ASA and
      clopidogrel non-response, well-designed clinical prospective trials are required
      to identify patients with antiplatelet drug resistance. Furthermore, mechanisms
      explaining this phenomenon of drug resistance are still unknown.

PMID- 16906242
TI  - [Longterm treatment of POAD with anticoagulants and platelet inhibitors after
      endovascular procedures and vascular surgery: what is evidence based?].
AB  - Platelet inhibitors and anticoagulants are used in the longterm treatment after
      successful infrainguinal bypass grafts as well as endovascular revascularisation
      procedures. However, evidence of the usefulness of these therapies is limited
      with respect to efficiency (patency rate, mortality) and safety (bleeding
      tendency) concerning these indications. Sufficient data are only available for
      acetylsalicylic acid treatment after implantation of prosthetic bypass grafts,
      the data basis for the use of antithrombotic medication in venous bypass grafts
      or following successful balloon angioplasty with or without stent implantation
      is, however, inconclusive. The recommendation for lifelong therapy with
      acetylsalicylic acid after infrainguinal bypass surgery and endovascular
      treatment is based mainly on the concept of prophylactic treatment of manifest
      atherosclerotic disease.

PMID- 16906243
TI  - [Gene therapy and stem cell transplantation in PAD].
AB  - Therapeutic angiogenesis is a novel promising strategy that uses angiogenic
      factors and stem cell transplantation to increase blood perfusion in ischaemic
      lower limbs. In preliminary studies short term safety and feasibility of gene
      therapy by recombinant protein administration or gene transfer were proven. Early
      reports mostly fail to show an convincing efficacy. In the largest placebo
      controlled study of therapeutic angiogenesis in severe PAD reported to date, the
      plasmid-based fibroblast growth factor was safe and significantly reduced
      amputation rates. The data suggest the efficacy of the angiogenic therapy and
      provide the basis for further larger trials to confirm these first results.

PMID- 16906244
TI  - Clinical and laboratory findings related to a favorable evolution of hantavirus
      pulmonary syndrome.
AB  - The medical records of 27 patients with hantavirus pulmonary syndrome were
      analyzed according to the need for invasive mechanical ventilation in relation to
      the following data up on hospital admission: age, gender, fever, cough, dyspnea,
      systolic arterial blood pressure, heart rate, levels of hemoglobin, hematocrit,
      leukocytes, lymphocytes, platelets, creatinine and arterial blood gases. The
      volume infused during the first 24 hours after admission, the use of inotropic
      agents, the use of corticosteroids and the patient outcomes were also evaluated.
      A favorable outcome was related to systolic blood pressure(3) 100 mmHg, heart
      rate lower than 100 beats per minute, creatinine below 1.6 mg/dl, arterial blood
      pH(3) 7.35, bicarbonate higher than 15 mEq/dl, oxygen saturation higher than
      84.1%, lower rehydration volume in the first 24 hours of hospitalization and no
      use of inotropic agents. Absence of clinical and laboratory signs of circulatory
      shock up on admission was associated with a favorable outcome of the patients.

PMID- 16906245
TI  - Viability and molecular authentication of Coccidioides immitis strains from
      culture collection of the Instituto Oswaldo Cruz, Rio de Janeiro, Brazil.
AB  - Twenty Coccidioides immitis strains were evaluated. Only 5 of the 20 strains kept
      under mineral oil maintained their viability while all 5 subcultures preserved in
      water remained viable and none of the 13 subcultures kept in soil were viable. A
      519 bp PCR product from the csa gene confirmed the identity of the strains.

PMID- 16906246
TI  - [Clinical profile of Chagas and non-Chagas' disease patients with cardiac
      pacemaker].
AB  - The aim of this study was to compare Chagas and non-Chagas' disease patients
      using single or dual-chamber pacemaker in relation to the ejection fraction of
      the left ventricle, the ventricular stimulation threshold and the occurrence of
      ventricular arrhythmia. From January, 2001 to November, 2002, 45 Chagas' disease
      patients and 35 non-Chagas' disease patients, all pacemaker users, were evaluated
      considering clinical history, echocardiographic study, Holter monitoring and
      analysis of the pacemaker telemetry data. Chagas' disease patients were
      significantly younger, but both groups were similar when chest X-Ray variables
      and right ventricular stimulation threshold were analyzed. Chagas' disease
      patients had a lower left ventricular ejection fraction and more frequent
      ventricular arrhythmia during Holter monitoring. A positive correlation between
      the low ejection fraction of the left ventricle and the intensity of ventricular
      arrhythmia was observed. In conclusion, among pacemaker user patients, Chagas'
      disease is related to cardiac markers of worse prognosis.

PMID- 16906247
TI  - [Aspects of the focal transmission of malaria in the Island of Sao Luis,
      Maranhao].
AB  - The aim of the study was to typify a malaria focus in Guarapiranga, in the
      district of Sao Jose de Ribamar, MA. A questionnaire regarding identification,
      economic situation, habits of the residents and characteristic of the residences
      was applied to each family. Fifty four families were visited and 207 inhabitants
      were interviewed (113 men and 95 women); 95 individuals were aged between 5 and
      24 years old. Agriculture and fishing are the basis of the local economy; 64.8%
      of the families earn less than one living wage. The majority of the residences
      are constructed of mud walls, straw roofs, a beaten earth floor, with no basic
      sanitation. 62.2% of the residences are partially protected against the entry of
      mosquitoes. Water for domestic use comes from natural waterholes in 78.8% of the
      residences. Rubbish is left in the open air in 53.7% of the residences. 106 cases
      of malaria by Plasmodium vivax were notified. Anopheles (N) aquasalis was the
      probable vector and treatment with chloroquine associated with primaquine showed
      good results.

PMID- 16906248
TI  - [Cryptococosis: clinical epidemiological laboratorial study and fungi varieties
      in 96 patients].
AB  - Ninety-six patients with cryptococcosis confirmed by clinical and laboratorial
      diagnosis were assessed in a prospective study in a University Hospital from
      March 1998 to November 2003; of these, 81.3% were HIV seropositive patients.
      Cryptococcus neoformans was isolated from different samples, of which the
      cerebrospinal fluid 74 (77%) was the most frequent. C. neoformans var neoformans
      was isolated in 89 cases, where as C. neoformans var gattii was isolated in 7.
      Cryptococcal meningoencephalitis was detected in 56.3% cases. It was the most
      frequent unique clinical manifestation and the fungus was detected in the
      bloodstream in 13.5% of the patients. Among the risk factors, AIDS (81.3%) was
      the most frequently associated with mycosis. Direct examination carried out on
      121 samples revealed the microorganism in 98.3% of them, while the culture was
      positive for all samples. Most of the patients (59.4%) were treated with
      amphotericin B or with triazoles, however 72.9% of them ended in death, in
      particular those patients with positive tests for the HIV (62.5%). Nowadays,
      cryptococcosis has been frequently diagnosed in our region and represents one of
      the opportunistic diseases with the highest morbidity and mortality rates in
      patients with AIDS.

PMID- 16906249
TI  - [Aedes aegypti resistance to temefos in counties of Ceara State].
AB  - The susceptibility of Aedes aegypti to temefos was evaluated by means of samples
      of eggs and larvae from four large counties in the state of Ceara (Fortaleza,
      Barbalha, Juazeiro do Norte and Crato). The technique standardized by the World
      Health Organization for tests with larvicides was used. The CL50 of eight samples
      from populations of Aedes was determined, as were their respective resistance
      ratios, compared to the CL50 of the susceptible Rockefeller strain. All
      populations submitted to the experiment showed resistance to temefos, with
      resistance ratios varying between 8 and 16. Analysis of these results reinforces
      prior evidence regarding the dissemination of temefos resistance in different
      locations in the state, subjected to considerable pressure for control in recent
      decades. The larvicide may lose its effectiveness if an urgent attempt is not
      made to reestablish the susceptibility of Aedes aegypti in these areas,
      profoundly affecting control campaigns currently under way.

PMID- 16906250
TI  - Meningoencephalitis by Naegleria fowleri: epidemiological study in Anzoategui
      state, Venezuela.
AB  - A case of primary amoebic meningoencephalitis produced by Naegleria fowleri was
      diagnosed in the Independencia county of Anzoategui State, Venezuela. This case
      motivated the realization of the present epidemiological study with the aim of
      identifying free-living amoebae in this area. Representative water samples were
      taken and physicochemical and microbiologic analyses were carried out.
      Trophozoites and cysts of Naegleria spp, were detected in 44.4% (n=4). An
      excellent concordance was found among the observations of free-living amoebae in
      smears and those of monoxenic cultures in non-nourishing agar with Klebsiella
      pneumoniae (Kappa=1; p= 0.003). A variable load of aerobic mesophils was
      obtained. Moulds and yeast averages presented 3.0 CFU/ml (SD +/- 2.0) and 102.9
      CFU/ml (SD +/- 32.2), respectively. One hundred per cent of the samples presented
      a most probable number of total and fecal coliforms of 240,000 NMP/100mL.
      Naegleria spp was present in waters of the Independence county of Anzoategui
      state, which constitutes a risk for people that use these sources.

PMID- 16906251
TI  - [Occurrence of dermatophyte, in nails, feet and hands of university students].
AB  - The objective of this paper was to evaluate the occurrence of dermatophytes,
      specifically in the nails, feet and hands of university students with and without
      lesions. Two hundred and eighty samples were collected; 31 (11.1%) were positive
      by direct examination, while only 20 (7.1%) showed dermatophyte growth in
      culture, as well as direct positive examination. Trichophyton rubrum was the most
      frequently isolated (80%) dermatophyte followed by T. mentagrophytes (20%).
      Considering the sites analyzed, dermatophyte occurrence was: 10.4% in toenails,
      5% in foot skin, 2.5% in fingernails and 0.4% in hand skin.

PMID- 16906252
TI  - Clinical and laboratorial evaluation of urinary schistosomiasis in Brazilians
      after staying in Mozambique.
AB  - We examined 87 Brazilian individuals of a group of 132 that, on July and November
      1994, participated in a peace mission in Mozambique. They served in an endemic
      area for haematobic schistosomiasis, where they swam in Licungo river during
      leisure time. Their arithmetic mean age was 31 year and all of them were male.
      Their urine test showed that 30 (34.5%) eliminated S. haematobium eggs and 55
      (63.2%) presented positive serology by the enzyme-linked immunoelectrotransfer
      blot test with purified microsomal antigen of S. haematobium adult worms.
      Eosinophilia was found in 30 (34.5%), haematuria in 26 (29.9%), dysuria in 32
      (36.8%) and lumbar pain in 36 (41.4%). All of those that eliminated eggs through
      urine had positive serology. Among the 25 patients with positive serology and
      without S. haematobium eggs in the urine test, 13 were symptomatic and 12
      asymptomatic. The treatment with praziquantel for the 30 patients, with urine
      positive to S. haematobium eggs, presented 70% of parasitological cure.

PMID- 16906253
TI  - [Perspectives of vector borne diseases control in Brazil].
AB  - The analysis of vector borne disease control in Brazil should consider three
      aspects: the urbanization of the population, change from a rural pattern to
      concomitant urban or peri-urban transmission and decentralization of control to
      municipalities. The great majority of the population now lives in urban areas.
      Some diseases are being transmitted in urban areas, due to the emergence or
      reemergence of their vectors, such as dengue, malaria and visceral leishmaniasis.
      Difficulties in control occur, as it is easier to apply control measures in rural
      areas, because there is more population adherence than in urban areas and so the
      coverage is higher and disease control is better. The decentralization of control
      activities to states and municipalities is being implemented and difficulties
      occur as these levels of government have insufficient accumulated experience in
      control. For more effective control, political commitment, multi-sector
      articulation and rational use of insecticide are required.

PMID- 16906254
TI  - [Spinal tuberculosis (Pott's disease) associated to psoas abscess: report of two
      cases and a literature review].
AB  - Tuberculosis is one of the most important infectious disease worldwide, with 3,9
      million reported cases in the world in 2002. The skeletal form is responsible for
      3% of the total number of cases, with 50% of these due to spinal tuberculosis.
      The psoas abscess is a rare clinical entity with approximately 12 cases per year
      described in the medical literature and has in the Mycobacterium tuberculosis ,
      one of its etiologic agents. The objective of this work is to report two cases of
      spinal tuberculosis associated with psoas abscess attended at our service, as
      well as a review of the literature.

PMID- 16906256
TI  - [Schistosomiasis mansoni simulating bladder neoplasia].
AB  - A 36-year-old patient, proceeding from an endemic area was admitted with episodes
      of total microscopic hematuria and terminal dysuria. Cytoscopy showed a
      protuberant tumor in the bladder anterior wall, suggestive of cancer. Biopsy
      revealed schistosomiasis mansoni. Transurethral resection confirmed the
      diagnosis. The patient was clinically treated and cured with oxamniquine. The
      case presented in this work emphasizes that not all the tumors of bladder with
      microscopic hematuria are bladder cancers.

PMID- 16906255
TI  - [The tumoral form of cerebellar schistosomiasis: case report and measure of
      granulomas].
AB  - An unusual case of the tumoral form of cerebellar Schistosomiasis mansoni, in a
      15 year-old male diagnosed by biopsy, with neurological signs and symptoms 60
      days prior to surgery. Computerized tomography show a hyperdense expanding lesion
      located in cerebellum, suggesting glioma. Histopathological examination showed
      numerous S. mansoni ova involved by granulomatous inflammation in necrotic
      exudative phase, located mainly in the internal, granular layer of the
      cerebellum, creating a pseudotumor in the cerebellar vermis and a recent
      hemorrhage in the trunk. The areas of granulomas were measured.

PMID- 16906257
TI  - [Comments on two cases of botulism in the State of Bahia, Brazil].
AB  - A report on two cases of botulism, one fatal, in which disease diagnosis was
      difficult and collaboration between public health and epidemiological
      surveillance services was poor. The objective of this report is to warn
      professionals of the seriousness of this disease and to reflect on existing
      public health surveillance practices.

PMID- 16906258
TI  - [Presence of IgM antibodies for Leptospira interrogans in wild animals from
      Tocantins State, 2002].
AB  - Four hundred and twenty-seven serum samples of wild animals were tested against
      18 serovars of Leptospira interrogans. Of 286 samples of Cebus apella, 46 (16.1%)
      were positive for the serovars pomona, brasiliensis, mini, swajizak,
      grippotyphosa, sarmin, fluminense, autumnalis, hebdomadis, guaratuba, javanica
      and icterohaemorrhagiae. Of 82 samples of Alouatta caraya, 2 (2.4%) were positive
      for the serovars mangus and fluminense. Of 31 samples of Nasua nasua, 4 (12.9%)
      were positive for the serovars fluminense and javanica, and of 10 samples of
      Cerdocyon thous, 2 (20 %) were positive for the serovars fluminense and
      brasiliensis. Seven samples of Dasyprocta sp, 6 of Tamandua tetradactyla and 5 of
      Euphractus sexcintus did not present reactivity.

PMID- 16906259
TI  - Pulmonary hypertension in schistosomiasis mansoni.

PMID- 16906261
TI  - [2nd meeting intergovernmental initiative of Chagas' disease surveillance and
      prevention in Amazonia].

PMID- 16906260
TI  - [Guidelines in paracoccidioidomycosis].

PMID- 16906262
TI  - [Vanize de Oliveira Macedo: 1934-2006].

PMID- 16906263
TI  - [Weight loss (although apparently modest) and physical exercise: two powerful
      weapons for the reduction of risk factors for coronary artery disease].

PMID- 16906264
TI  - [Effects of acute exercise on postprandial lipemia in sedentary men].
AB  - OBJECTIVE: To examine the effects of a single session of isometric physical
      exercise on postprandial triglyceridemia in sedentary male individuals with
      fasting triglycerides values < 150 mg/dl (NTG) or > " 150 mg/dl (TG ALT).
      METHODS: Twenty-seven individuals (10 NTG and 17 TG ALT), aged between 30-55
      years were assessed in the study. Triglycerides were determined in the beginning,
      and at two, four and six hours after the oral ingestion of a solution with 50
      g/m2 of fat in two occasions: at rest and after treadmill isometric exercise.
      RESULTS: Acute exercise did not affect the levels of postprandial triglycerides
      or the area under the curve (AUC) of triglycerides. However, the abnormal pattern
      of postprandial lipemia curve was associated with higher basal triglyceridemia
      with exercise (basal TG: 147 +/- 90 vs. 238 +/- 89 mg/dl, p = 0.02) and without
      exercise (basal TG: 168 +/- 93 vs. 265 +/- 140 mg/dl, p = 0.04). Analysis of the
      receiver operating characteristics (ROC) curves showed cut-off values for basal
      triglycerides with exercise of 166.5 mg/dl (sensitivity: 0.78; specificity: 0.72)
      and AUC of 0.772 [CI 95%: 0.588-0.955], and without exercise of 172 mg/dl
      (sensitivity: 0.78; specificity: 0.61) and AUC: 0.722 [CI 95%: 0.530-0.914].
      CONCLUSION: Acute exercise did not affect postprandial triglyceridemia in
      sedentary male individuals, and basal triglyceride levels are predictors of an
      abnormal response of postprandial triglycerides.

PMID- 16906265
TI  - [Effects of greater-than-5% weight reduction on hemodynamic, metabolic and
      neuroendocrine profiles of grade I obese subjects].
AB  - OBJECTIVE: To evaluate the effects of a greater-than-5% weight reduction in
      hemodynamic, metabolic, and neuroendocrine profiles of grade I obese subjects.
      METHODS: Observational study with 47 grade I obese subjects, with mean age of 33
      years who received monthly orientation regarding diet, physical exercises, and
      eating behavior for four months. Blood pressure using the auscultatory method and
      pulse rate were assessed monthly, whereas the following variables (and respective
      methods) were measured at the beginning and at the end of the study: total
      cholesterol, triglycerides, HDL-cholesterol (enzymatic method), LDL-cholesterol
      (Friedewald formula), blood glucose (hexokinase method), leptin, adiponectin,
      renin, aldosterone, insulin (radioimmunoassay) and insulin-resistance index
      (HOMA). RESULTS: After adjustment for other variables, significant reductions of
      6 mmHg in diastolic blood pressure, 7 pg/ml in renin, 13 mg/dl in total
      cholesterol and 12 mg/dl in LDL-cholesterol were observed in the greater-than-5%
      weight reduction group. Also, a tendency to a higher increase in adiponectin
      levels by the end of the study, as well as a three-fold higher reduction in blood
      glucose, insulin, and HOMA levels, and a six-fold higher reduction in leptin
      levels were observed in this group. CONCLUSION: Non-pharmacological measures that
      promote a greater-than-5% weight reduction produce hemodynamic, metabolic, and
      neuroendocrine effects that improve the cardiovascular risk of obese subjects.

PMID- 16906266
TI  - [Surgical treatment of aortic valve disease with stentless bovine pericardium
      prosthesis: immediate results].
AB  - OBJECTIVE: To present the immediate results and assess the clinical and
      hemodynamic performance of stentless bovine pericardial bioprostheses in aortic
      position. METHODS: Twenty patients were operated who were indicated for surgery
      for valve replacement with biological prosthesis. Eleven patients were male;
      sixteen had aortic stenosis; four, insufficiency; the mean age was 66.3 +/- 8.8
      years. The surgical technique used was subcoronary implant. Associated procedures
      were performed in five patients. Postoperative morbidity, mortality and
      hemodynamic performance were assessed on transthoracic echocardiogram. RESULTS:
      Mean time of cardiopulmonary bypass was 136.5 +/- 24.41 minutes and mean anoxic
      time was 105.2 +/- 21.62 minutes. Hospital mortality was 5% (one patient). Mean
      time of intensive care unit stay was 3.65 +/- 3.23 days. Mean postoperatively
      transvalvular gradient was was 25.39 +/- 7.82 mmHg. Left ventricle ejection
      fraction was 67 +/- 13.49% preoperatively and 63.24 +/- 16.06% postoperatively (p
      = 0.45). Eleven patients did not present any degree of valve regurgitation, eight
      presented mild regurgitation and one ,mild to moderate regurgitation. CONCLUSION:
      Stentless prostheses can be used for the surgical treatment of aortic valve
      diseases, with in hospital mortality and morbidity similar to the mortality and
      morbidity described in the literature for similar procedures, with satisfactory
      hemodynamic performance.

PMID- 16906267
TI  - [Inflammatory markers of atherosclerotic plaque stabilization after acute
      coronary event--temporal trends].
AB  - OBJECTIVE: To evaluate the length of time required for atherosclerotic plaque
      stabilization in acute coronary syndromes (ACS), using inflammatory markers.
      METHODS: In this prospective study, C-reactive protein (CRP), fibrinogen, factor
      VIIIc, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) levels
      were measured on admission, at discharge, and three and six months post-discharge
      in 40 patients with non-ST-segment elevation ACS (NSTE-ACS) and 40 healthy
      subjects. RESULTS: C-reactive protein levels were significantly higher on
      admission and at discharge, but not at three and six months post-discharge,
      compared with the control group. Fibrinogen levels remained unchanged, except at
      six months, when they were significantly lower than in the control group. Factor
      VIII-c did not differ from that of the control group on admission, but it was
      significantly higher at discharge, with no differences at three and six months.
      Interleukin-6 levels were significantly higher than in the control group in all
      time points. However, they declined significantly between discharge and three
      months. In no time point was TNF-alpha significantly different from that of the
      control group. Only IL-6 correlated significantly and independently with future
      cardiovascular events. CONCLUSION: With respect to CRP and factor VIIIc, plaque
      stabilization is suggested in up to three months; IL-6 analysis suggests
      stabilization as from the third month, although it remained higher than that of
      the control group for up to six months. Only IL-6 showed prognostic value for
      further events within a year.

PMID- 16906268
TI  - [Determinants of risk of cardiovascular diseases in schoolchildren].
AB  - OBJECTIVE: To investigate the occurrence and association of arterial hypertension
      with several lifestyle variables. METHODS: Transversal population-based study
      with a random sample of students (7 to 14 years of age) of public and private
      schools. Variables investigated were nutritional status, blood pressure, and
      lifestyle (tobacco use, alcohol intake, physical activity and eating habits).
      RESULTS: Out of the 3,169 schoolchildren assessed, 5.0% had arterial hypertension
      and 6.2% had normal-high blood pressure. Classification by gender shows boys 6.4%
      and girls 6.0% with normal-high blood pressure, and boys 4.3% and girls 5.7% with
      arterial hypertension. Body mass index (BMI) measurements identified 16.0% excess
      weight students, 4.9% of whom were obese. A significant association (p = 0.01)
      between arterial hypertension and excess weight was observed. Among the students
      participating in the study, 11.6% did not attend physical education classes and
      37.8% had sedentary leisure habits. Twenty students (0.6%) were smokers and 32.7%
      had already experimented with alcohol. None of these variables showed statistical
      significance as to blood pressure values and nutritional status. CONCLUSION: In
      light of the findings in this study which show schoolchildren with a higher than
      expected frequency of mean blood pressure and BMI values, associated with a
      lifestyle that tends to favour the development of cardiovascular diseases, we
      felt led to propose interventional measures focused on the school as an agent of
      change and capable of conveying information to family units. This possibility
      encourages us to propose that schools be partners in promoting health.

PMID- 16906269
TI  - [Arterial prehypertension and elevated pulse pressure in adolescents: prevalence
      and associated factors].
AB  - OBJECTIVE: To estimate the prevalence of prehypertension and elevated pulse
      pressure in adolescents and assess the association between those two conditions
      and sex, age, sexual development, obesity and physical activity. METHODS:
      Anthropometrical data and blood pressure were measured in and a questionnaire was
      applied to 456 adolescents (aged 12 to 17 years) recruited from public and
      private schools, in the Fonseca district, in the city of Niteroi, state of Rio de
      Janeiro, Brazil, from 2003 to 2004. RESULTS: Thirty nine (8.6%) presented
      prehypertension (PH) and 13.4%, elevated pulse pressure (PP). At bivariate
      analysis, PH was significantly associated with sex, age and obesity, with more
      prevalent in boys aged between 15 and 17 years, and in the obese. Elevated PP was
      associated with gender only, as it was more prevalent in boys. Sexual maturation
      did not show an association with PH or elevated PP. Similar correlations were
      found at logistic regression. PH prevalence odds ratio was 7.7 for sex, 4.3 for
      age and 4.6 for obesity. Elevated PP prevalence odds ratio was 10.8 for sex. The
      correlation between PP and physical activity was positive and significant. The
      elevation of PP was attributable to systolic blood pressure. CONCLUSION: PH and
      the elevated PP were shown to be present in adolescents from a population with a
      low prevalence of hypertension, mostly in boys. Further prospective studies are
      necessary to assess the persistence and the impact of those conditions.

PMID- 16906270
TI  - [Swim training attenuates myocardial remodeling and the pulmonary congestion in
      wistar rats with secondary heart failure to myocardial infarction].
AB  - OBJECTIVE: To evaluate the effects of swimming on pulmonary water content in
      animals with heart failure (HF) after myocardial infarction (MI). METHODS: After
      coronary occlusion, MI size 20%<MI<40% of the left ventricle (LV) were considered
      moderate and those > 40% of the LV large. The animals swam for 60 min/day, 5
      days/week for 8 weeks. The wet weight of lung, liver, atriums, LV and right
      ventricle (RV) as well as the dry weight of the liver and lung were determined.
      ANOVA and Tukey test were used for statistical analysis. RESULTS: An increase in
      the atrium/body weight ratio was noted in the sedentary animals with moderate
      (MImod-SED: n=8) and large (MIlg-SED: n=10) infarctions in comparison to the
      sedentary control (C-SED: n=14) and trained (C-TR: n=16) rats. An increase in the
      RV/body weight and LV/body weight ratios was noted in the MIlg-SED. The
      heart/body weight ratio was higher in MIlg-SED when compared to the other groups.
      The infarcted trained animals presented diminished hypertrophy. The pulmonary
      water content was higher in MIlg-SED animals (81+/-0.4%) than in C-SED animals
      (79+/-0.4%). No differences were found for the other comparisons (C-TR: 79+/
      0.4%; MImod-SED: 80+/-0.3%; MImod-TR: 80+/-0.6%; MIlg-TR: 79+/-0.7%). CONCLUSION:
      The increase of cardiac mass and pulmonary water content presented by MIlg-SED
      was diminished in the trained animals. The results suggest that the practice of
      physical exercise can diminish HF and contribute to favorable cardiac remodeling.

PMID- 16906271
TI  - [Giant left atrium].

PMID- 16906272
TI  - [Case 3/2006--progressive respiratory failure in a 33 year-old man with heart
      disease and remarkable somatic dysmorphism].

PMID- 16906273
TI  - Brazilian medical publications: citation patterns for Brazilian-edited and non
      Brazilian literature.
AB  - Today, the quality of a scientific article depends on the periodical in which it
      is published and on the number of times the article is cited in the literature.
      In Brazil, the criteria for the evaluation of this scientific production are
      improving. However, there is still some resistance, with authors arguing that
      Brazilian publications must be preferentially addressed to the national readers
      and, therefore, they should ideally be written in Portuguese. In order to
      determine the kind of scientific journals cited in the reference lists of
      articles published in medical periodicals edited in Brazil, in the present study
      we determine the rate of Portuguese/English citations. Three issues of 43
      periodicals (19 indexed in SciELO, 10 in PubMed, 10 in LILACS, and 4 in the ISI
      Thompson base) of different medical specialties were analyzed, and the number of
      both Portuguese and English citations in the reference list of each article was
      recorded. The results showed that in Brazilian-edited journals the mean number of
      citations/article was 20.9 +/- 6.9 and the percentage of citations of
      international non-Brazilian periodicals was 86.0 +/- 11.2%. Of the latter, 94.4
      +/- 7.0 are indexed by ISI-Thompson. Therefore, we conclude that Brazilian
      medical scientists cite the international non-Brazilian periodicals more than the
      national journals, and most of the cited papers are indexed by ISI-Thompson.

PMID- 16906274
TI  - Novel mechanisms of growth hormone regulation: growth hormone-releasing peptides
      and ghrelin.
AB  - Growth hormone secretion is classically modulated by two hypothalamic hormones,
      growth hormone-releasing hormone and somatostatin. A third pathway was proposed
      in the last decade, which involves the growth hormone secretagogues. Ghrelin is a
      novel acylated peptide which is produced mainly by the stomach. It is also
      synthesized in the hypothalamus and is present in several other tissues. This
      endogenous growth hormone secretagogue was discovered by reverse pharmacology
      when a group of synthetic growth hormone-releasing compounds was initially
      produced, leading to the isolation of an orphan receptor and, finally, to its
      endogenous ligand. Ghrelin binds to an active receptor to increase growth hormone
      release and food intake. It is still not known how hypothalamic and circulating
      ghrelin is involved in the control of growth hormone release. Endogenous ghrelin
      might act to amplify the basic pattern of growth hormone secretion, optimizing
      somatotroph responsiveness to growth hormone-releasing hormone. It may activate
      multiple interdependent intracellular pathways at the somatotroph, involving
      protein kinase C, protein kinase A and extracellular calcium systems. However,
      since ghrelin has a greater ability to release growth hormone in vivo, its main
      site of action is the hypothalamus. In the current review we summarize the
      available data on the: a) discovery of this peptide, b) mechanisms of action of
      growth hormone secretagogues and ghrelin and possible physiological role on
      growth hormone modulation, and c) regulation of growth hormone release in man
      after intravenous administration of these peptides.

PMID- 16906275
TI  - Depressive symptoms and C-reactive protein in a Brazilian urban community.
AB  - Psychological depression is an independent risk factor for coronary artery
      disease. C-reactive protein has been implicated as a mediator of the effect of
      psychological depression. Several studies have found that individuals, especially
      men, who report higher levels of psychological depression also have higher levels
      of C-reactive protein. The current study was undertaken to replicate these
      results in a Brazilian population, in which there is a much wider range of
      variation in both background characteristics (such as socioeconomic status) and
      coronary artery disease risk factors. A sample of 271 individuals was interviewed
      using the Center for Epidemiological Studies Depression Scale. Fasting blood
      samples were obtained and evaluated for C-reactive protein (assessed by a
      turbidimetric immunoassay using a Dade Behring kit) analysis in a subsample (N =
      258) of individuals. The mean +/- SD C-reactive protein for the entire sample was
      0.43 +/- 0.44, with 0.42 +/- 0.48 for men and 0.43 +/- 0.42 mg/L for women. Data
      were analyzed using multiple regression analysis, controlling for age, sex, body
      mass index, socioeconomic status, tobacco use, and both total cholesterol and low
      density lipoprotein cholesterol. Higher reported depressive symptoms were
      correlated with higher C-reactive protein for men (partial r = 0.298, P = 0.004)
      and with lower C-reactive protein for women (partial r = -0.154, P = 0.059). The
      differences in the associations for men and women could be a result of
      differential effects of sex hormones on stress reactivity and immune response. On
      the other hand, this difference in the associations may be related to gender
      differences in the disclosure of emotion and the effect that self-disclosure has
      on physical health and immune response.

PMID- 16906276
TI  - Elevated amniotic fluid amino acid levels in fetuses with gastroschisis.
AB  - Our objective was to measure maternal plasma and amniotic fluid amino acid
      concentrations in pregnant women diagnosed as having fetuses with gastroschisis
      in the second trimester of pregnancy. Twenty-one pregnant women who had fetuses
      with gastroschisis detected by ultrasonography (gastroschisis group) in the
      second trimester and 32 women who had abnormal triple screenings indicating an
      increased risk for Down syndrome but had healthy fetuses (control group) were
      enrolled in the study. Amniotic fluid was obtained by amniocentesis, and maternal
      plasma samples were taken simultaneously. The chromosomal analysis of the study
      and control groups was normal. Levels of free amino acids and non-essential amino
      acids were measured in plasma and amniotic fluid samples using EZ:fast kits
      (EZ:fast GC/FID free (physiological) amino acid kit) by gas chromatography (Focus
      GC AI 3000 Thermo Finnigan analyzer). The mean levels of essential amino acids
      (histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine,
      tryptophan, and valine) and non-essential amino acids (alanine, glycine, proline,
      and tyrosine) in amniotic fluid were found to be significantly higher in fetuses
      with gastroschisis than in the control group (P < 0.05). A significant positive
      correlation between maternal plasma and amniotic fluid concentrations of
      essential and nonessential amino acids was found only in the gastroschisis group
      (P < 0.05). The detection of significantly higher amino acid concentrations in
      the amniotic fluid of fetuses with a gastroschisis defect than in healthy fetuses
      suggests the occurrence of amino acid malabsorption or of amino acid leakage from
      the fetus into amniotic fluid.

PMID- 16906277
TI  - Primary and secondary esophageal contractions in patients with gastroesophageal
      reflux disease.
AB  - We studied the primary and secondary esophageal peristalsis in 36 patients with
      heartburn and acid regurgitation and in 14 asymptomatic volunteers. Primary
      peristalsis was elicited by ten swallows of a 5-mL bolus of water and secondary
      peristalsis was elicited by intra-esophageal infusion of 5, 10, and 15 mL water,
      0.1 N hydrochloric acid and air. Esophageal contractions were measured by an 8
      lumen manometric catheter assembly incorporating a 6-cm sleeve device.
      Contractions were registered at 3, 9, and 15 cm from the upper margin of the
      sleeve and the infusion was done through a side hole located at 12 cm. Twenty
      patients had normal endoscopic esophageal examination, 10 with normal (group I)
      and 10 with abnormal pH-metric examination (group II), and 16 had esophagitis
      (group III). The amplitude of contractions after swallows was lower (97.8 +/-
      10.0 mmHg) in the distal esophagus of group III patients than in controls (142.3
      +/- 14.0 mmHg). Patients of group III had fewer secondary contractions (water:
      25% of infusion) than patients of the other groups and controls (67% of
      infusion). Patients of group III also had a lower amplitude of secondary
      peristalsis in the distal esophagus (water: 70.1 +/- 9.6 mmHg) than controls
      (129.2 +/- 18.2 mmHg). We conclude that patients with esophagitis have an
      impairment of primary and secondary peristalsis in the distal esophagus.

PMID- 16906278
TI  - Proliferative diabetic retinopathy is associated with microalbuminuria in
      patients with type 2 diabetes.
AB  - Diabetic retinopathy is one of the leading causes of blindness in working-age
      individuals. Diabetic patients with proteinuria or those on dialysis usually
      present severe forms of diabetic retinopathy, but the association of diabetic
      retinopathy with early stages of diabetic nephropathy has not been entirely
      established. A cross-sectional study was conducted on 1214 type 2 diabetic
      patients to determine whether microalbuminuria is associated with proliferative
      diabetic retinopathy in these patients. Patients were evaluated by direct and
      indirect ophthalmoscopy and grouped according to the presence or absence of
      proliferative diabetic retinopathy. The agreement of diabetic retinopathy
      classification performed by ophthalmoscopy and by stereoscopic color fundus
      photographs was 95.1% (kappa = 0.735; P < 0.001). Demographic information,
      smoking history, anthropometric and blood pressure measurements, glycemic and
      lipid profile, and urinary albumin were evaluated. On multiple regression
      analysis, diabetic nephropathy (OR = 5.18, 95% CI = 2.91-9.22, P < 0.001),
      insulin use (OR = 2.52, 95% CI = 1.47-4.31, P = 0.001) and diabetes duration (OR
      = 1.04, 95% CI = 1.01-1.07, P = 0.011) were positively associated with
      proliferative diabetic retinopathy, and body mass index (OR = 0.90, 95% CI = 0.86
      0.96, P < 0.001) was negatively associated with it. When patients with
      macroalbuminuria and on dialysis were excluded, microalbuminuria (OR = 3.3, 95%
      CI = 1.56-6.98, P = 0.002) remained associated with proliferative diabetic
      retinopathy. Therefore, type 2 diabetic patients with proliferative diabetic
      retinopathy more often presented renal involvement, including urinary albumin
      excretion within the microalbuminuria range. Therefore, all patients with
      proliferative diabetic retinopathy should undergo an evaluation of renal function
      including urinary albumin measurements.

PMID- 16906279
TI  - Health in early adulthood: the contribution of the 1978/79 Ribeirao Preto birth
      cohort.
AB  - The increase in non-communicable chronic diseases of adults is due to demographic
      changes and changes in the risk factors related to physical activity, smoking
      habits and nutrition. We describe the methodology for the evaluation of persons
      at 23/25 years of age of a cohort of individuals born in Ribeirao Preto in
      1978/79. We present their socioeconomic characteristics and the profile of some
      risk factors for chronic diseases. A total of 2063 participants were evaluated by
      means of blood collection, standardized questionnaires, anthropometric and blood
      pressure measurements, and methacholine bronchoprovocation tests. The sexes were
      compared by the chi-square test, with alpha = 0.05. Obesity was similar among men
      and women (12.8 and 11.1%); overweight was almost double in men (30.3 vs 17.7%).
      Weight deficit was higher among women than among men (8.6 and 2.6%). Women were
      more sedentary and consumed less alcohol and tobacco. Dietary fat consumption was
      similar between sexes, with 63% consuming large amounts (30 to 39.9 g/day).
      Metabolic syndrome was twice more frequent among men than women (10.7 vs 4.8%),
      hypertension was six times more frequent (40.9 vs 6.4%); altered triglyceride
      (16.1 vs 9.8%) and LDL proportions (5.4 vs 2.7%) were also higher in men, while
      women had a higher percentage of low HDL (44.7 vs 39.5%). Asthma and bronchial
      hyper-responsiveness were 1.7 and 1.5 times more frequent, respectively, among
      women. The high prevalence of some risk factors for chronic diseases among young
      adults supports the need for investments in their prevention.

PMID- 16906280
TI  - Repercussions of a sleep medicine outreach program.
AB  - Despite the high prevalence of sleep disorders, many healthcare professionals and
      lay people have little knowledge of Sleep Medicine. Mindful of such a reality, in
      2001 the Sleep Institute of the Associacao Fundo de Incentivo a Psicofarmacologia
      launched a campaign to increase Sleep Medicine awareness. Media features,
      exhibitions, inserts, and classes were used to reach 2,000,000 people and 55,000
      healthcare professionals during the period from 2001 to 2004. To evaluate this
      program, we compared data for polysomnography referrals to the Institute in 2000
      and in 2004. A total of 8805 referrals were evaluated (2000: 2164; 2004: 6641).
      Over the 4 years of the program, the number of beds increased by 43%; more women
      were referred (31 vs 37%; P < 0.001), mainly with a diagnostic hypothesis of
      sleep-disorder breathing (SDB). SDB was the most frequent diagnostic hypothesis
      in 2000 and 2004. In 2004 there were fewer referrals without a diagnostic
      hypothesis (27 vs 21%; P < 0.001) and for controlling surgically treated SDB (2.3
      vs 1.6%; P < 0.05), and an increase in the following diagnostic hypotheses: non
      invasive treatment of SDB (8.3 vs 12.3%; P < 0.001) and insomnia (3.5 vs 6.5%; P
      < 0.001). Insomnia diagnostic hypothesis was better correlated with SDB on
      referral documents in 2004 and less with a diagnostic hypothesis of limb movement
      disturbance. The program helped increase polysomnography referrals, particularly
      among women. Healthcare professionals appear to have a more developed
      understanding of sleep disorders.

PMID- 16906281
TI  - Urinary NO3 excretion and renal failure in indinavir-treated patients.
AB  - Treatment with indinavir (IDV), a protease inhibitor, is frequently associated
      with renal abnormalities. We determined the incidence of renal failure
      (creatinine clearance <80 mL min-1 1.73 (m(2))-1) in HIV patients treated with
      highly active antiretroviral therapy, including IDV, and investigated the
      possible mechanisms and risk factors of IDV nephrotoxicity. Thirty-six patients
      receiving IDV were followed for 3 years. All were assessed for age, body weight,
      duration of infection, duration of IDV treatment, sulfur-derivative use, total
      cholesterol, triglycerides, magnesium, sodium, potassium, creatinine, and
      urinalysis. We also determined renal function in terms of creatinine clearance,
      urine osmolality and fractional excretion of sodium, potassium, and water.
      Urinary nitrate (NO3) excretion was measured in 18 IDV-treated patients and
      compared with that of 8 patients treated with efavirenz, a drug without renal
      side effects. Sterile leukocyturia occurred in 80.5% of the IDV-treated patients.
      Creatinine clearance <80 mL min-1 1.73 (m(2))-1 was observed in 22 patients (61%)
      and was associated with low body weight and the use of sulfur-derivatives. These
      patients also had lower osmolality, lower urine volume and a higher fractional
      excretion of water compared to the normal renal function group. Urinary NO3
      excretion was significantly lower in IDV-treated patients (809 +/- 181 microM NO3
      /mg creatinine) than in efavirenz-treated patients (2247 +/- 648 microM NO3-/mg
      creatinine, P < 0.01). The lower NO3 excretion suggests that IDV decreases nitric
      oxide production.

PMID- 16906282
TI  - An immunohistochemical, clinical and electroneuromyographic correlative study of
      the neural markers in the neuritic form of leprosy.
AB  - The nerve biopsies of 11 patients with pure neuritic leprosy were submitted to
      routine diagnostic procedures and immunoperoxidase staining with antibodies
      against axonal (neurofilament, nerve growth factor receptor (NGFr), and protein
      gene product (PGP) 9.5) and Schwann cell (myelin basic protein, S-100 protein,
      and NGFr) markers. Two pairs of non-adjacent histological cross-sections of the
      peripheral nerve were removed for quantification. All the fascicles of the nerve
      were examined with a 10X-ocular and 40X-objective lens. The immunohistochemistry
      results were compared to the results of semithin section analysis and clinical
      and electroneuromyographic data. Neurofilament staining was reduced in 100% of
      the neuritic biopsies. NGFr positivity was also reduced in 81.8%, PGP staining in
      100% of the affected nerves, S100 positivity in 90.9%, and myelin basic protein
      immunoreactivity in 90.9%. Hypoesthesia was associated with decreased NGFr
      (81.8%) and PGP staining (90.9%). Reduced potential amplitudes
      (electroneuromyographic data) were found to be associated with reduced PGP 9.5
      (63.6%) and nerve fiber neurofilament staining (45.4%) by immunohistochemistry
      and with loss of myelinated fibers (100%) by semithin section analysis. On the
      other hand, the small fibers (immunoreactive dots) seen amid inflammatory cells
      continued to be present even after 40% of the larger myelinated fibers had
      disappeared. The present study shows an in-depth view of the destructive effects
      of leprosy upon the expression of neural markers and the integrity of nerve
      fiber. The association of these structural changes with the clinical and
      electroneuromyographic manifestations of leprosy peripheral neuropathy was also
      discussed.

PMID- 16906283
TI  - Prevalence of serological markers of hepatitis B virus in pregnant women from
      Parana State, Brazil.
AB  - The prevalence of hepatitis B virus (HBV) in Brazil increases from South to North
      but moderate to elevated prevalence has been detected in the Southwest of Parana
      State. The prevalence of serological markers of HBV was evaluated in 3188
      pregnant women from different counties in Parana State and relevant
      epidemiological features were described. The prevalence of HBV markers in
      pregnant women for the state as a whole was 18.5% (95% CI = 17.2-19.9), ranging
      from 7.2% in Curitiba to 38.5% in Francisco Beltrao. The endemicity of HBV marker
      prevalence in pregnant women was intermediate in Cascavel, Foz do Iguacu, and
      Francisco Beltrao, and low in Curitiba, Londrina, Maringa, and Paranagua.
      Multiple logistic regression showed that HBV marker prevalence increased with
      age, was higher among black women, among women of Italian and German descent, and
      among women who had family members in neighboring Rio Grande do Sul State.
      Univariate analysis showed that HBV marker prevalence was also higher among women
      with no education or only primary education, with a lower family income and whose
      families originated from the South Region of Brazil. Pregnant women not having
      positive HBV markers (anti-HBc, HBsAg or anti-HBs detected by ELISA) corresponded
      to 73.7% of the population studied, implying that HBV vaccination needs to be
      reinforced in Parana State. The highest prevalence was found in three counties
      that received the largest number of families from Santa Catarina and Rio Grande
      do Sul, where most immigrants were of German or Italian ascendance. This finding
      probably indicates that immigrants that came to this area brought HBV infection
      to Southwestern Parana State.

PMID- 16906284
TI  - The effect of performing corrections on reported uterine cancer mortality data in
      the city of Sao Paulo.
AB  - Reports of uterine cancer deaths that do not specify the subsite of the tumor
      threaten the quality of the epidemiologic appraisal of corpus and cervix uteri
      cancer mortality. The present study assessed the impact of correcting the
      estimated corpus and cervix uteri cancer mortality in the city of Sao Paulo,
      Brazil. The epidemiologic assessment of death rates comprised the estimation of
      magnitudes, trends (1980-2003), and area-level distribution based on three
      strategies: i) using uncorrected death certificate information; ii) correcting
      estimates of corpus and cervix uteri mortality by fully reallocating unspecified
      deaths to either one of these categories, and iii) partially correcting specified
      estimates by maintaining as unspecified a fraction of deaths certified as due to
      cancer of "uterus not otherwise specified". The proportion of uterine cancer
      deaths without subsite specification decreased from 42.9% in 1984 to 20.8% in
      2003. Partial and full corrections resulted in considerable increases of cervix
      (31.3 and 48.8%, respectively) and corpus uteri (34.4 and 55.2%) cancer
      mortality. Partial correction did not change trends for subsite-specific uterine
      cancer mortality, whereas full correction did, thus representing an early
      indication of decrease for cervical neoplasms and stability for tumors of the
      corpus uteri in this population. Ecologic correlations between mortality and
      socioeconomic indices were unchanged for both strategies of correcting estimates.
      Reallocating unspecified uterine cancer mortality in contexts with a high
      proportion of these deaths has a considerable impact on the epidemiologic profile
      of mortality and provides more reliable estimates of cervix and corpus uteri
      cancer death rates and trends.

PMID- 16906285
TI  - Gene expression profiling of clinical stages II and III breast cancer.
AB  - Clinical stage (CS) is an established indicator of breast cancer outcome. In the
      present study, a cDNA microarray platform containing 692 genes was used to
      identify molecular differences between CSII and CSIII disease. Tumor samples were
      collected from patients with CSII or CSIII breast cancer, and normal breast
      tissue was collected from women without invasive cancer. Seventy-eight genes were
      deregulated in CSIII tumors and 22 in CSII tumors when compared to normal tissue,
      and 20 of them were differentially expressed in both CSII and CSIII tumors. In
      addition, 58 genes were specifically altered in CSIII and expression of 6 of them
      was tested by real time RT-PCR in another cohort of patients with CSII or CSIII
      breast cancer and in women without cancer. Among these genes, MAX, KRT15 and
      S100A14, but not APOBEC3G or KRT19, were differentially expressed on both CSIII
      and CSII tumors as compared to normal tissue. Increased HMOX1 levels were
      detected only in CSIII tumors and may represent a molecular marker of this stage.
      A clear difference in gene expression pattern occurs at the normal-to-cancer
      transition; however, most of the differentially expressed genes are deregulated
      in tumors of both CS (II and III) compared to normal breast tissue.

PMID- 16906286
TI  - Effect of the consumption of tomato paste on plasma prostate-specific antigen
      levels in patients with benign prostate hyperplasia.
AB  - The consumption of tomatoes and tomato products has been associated with a
      reduced risk of prostate cancer. We observed a decrease of 10.77% in prostate
      specific antigen (PSA) levels in patients with benign prostate hyperplasia who
      were submitted to daily ingestion of tomato paste. This was an experimental
      rather than a controlled study with a sample of 43 men ranging in age from 45 to
      75 years, all with histological diagnoses of benign prostate hyperplasia and
      plasma PSA levels of 4-10 ng/mL. All patients received 50 g of tomato paste once
      a day for 10 consecutive weeks and PSA levels were analyzed before, during and
      after the consumption of tomato paste. ANOVA for repeated measures was used to
      compare PSA levels before, during and after the consumption of tomato paste. The
      mean +/- SD PSA level was 6.51 +/- 1.48 ng/mL at baseline and 5.81 +/- 1.58 ng/mL
      (P = 0.005) after 10 weeks. Acceptance was good in 88.3, regular in 9.3, and poor
      in 2.3% of the patients. Dietary ingestion of 50 g of tomato paste per day for 10
      weeks significantly reduced mean plasma PSA levels in patients with benign
      prostate hyperplasia, probably as a result of the high amount of lycopene in
      tomato paste. This was not a prostate cancer prevention study, but showed some
      action of tomato paste in prostate biology. The development of prostate cancer is
      typically accompanied by an increase in plasma PSA levels, thus any intervention
      that affects plasma PSA levels can suggest an impact in the progression of
      disease.

PMID- 16906287
TI  - Prolactin and cortisol levels in women with endometriosis.
AB  - Endometriosis is a progressive estrogen-dependent disease affecting women during
      their reproductive years. The objective of the present study was to investigate
      whether endometriosis is associated with stress parameters. We determined
      cortisol and prolactin levels in serum, peritoneal and follicular fluid from
      infertile women with endometriosis and fertile women without the disease. The
      extent of the disease was staged according to the revised American Fertility
      Society classification (1997). Serum and peritoneal fluid were collected from 49
      women aged 19 to 39 years undergoing laparoscopy. Eighteen women had stage I-II
      endometriosis and 10 had stage III-IV. Controls were 21 women undergoing
      laparoscopy for tubal sterilization. Follicular fluid was obtained from 39 women
      aged 25-39 years undergoing in vitro fertilization (21 infertile women with
      endometriosis and 18 infertile women without endometriosis). Serum prolactin
      levels were significantly higher in infertile women with stage III-IV
      endometriosis (28.9 +/- 2.1 ng/mL) than in healthy controls (13.2 +/- 2.1 ng/mL).
      Serum cortisol levels were significantly higher in infertile women with stage III
      IV endometriosis (20.1 +/- 1.3 ng/mL) than in controls (10.5 +/- 1.4 ng/mL).
      Cortisol and prolactin levels in follicular fluid and peritoneal fluid did not
      differ significantly between groups. The high levels of cortisol and prolactin in
      the serum from women with endometriosis might contribute to the subfertility
      frequently associated with the disease. Moreover, since higher levels of cortisol
      and prolactin are often associated with stress, it is probable that stress might
      contribute to the development of endometriosis and its progression to advanced
      stages of the disease.

PMID- 16906288
TI  - Striatal and extrastriatal atrophy in Huntington's disease and its relationship
      with length of the CAG repeat.
AB  - Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder
      that affects the striatum most severely. However, except for juvenile forms,
      relative preservation of the cerebellum has been reported. The objective of the
      present study was to perform MRI measurements of caudate, putamen, cerebral, and
      cerebellar volumes and correlate these findings with the length of the CAG repeat
      and clinical parameters. We evaluated 50 consecutive patients with HD using MRI
      volumetric measurements and compared them to normal controls. Age at onset of the
      disease ranged from 4 to 73 years (mean: 43.1 years). The length of the CAG
      repeat ranged from 40 to 69 (mean: 47.2 CAG). HD patients presented marked
      atrophy of the caudate and putamen, as well as reduced cerebellar and cerebral
      volumes. There was a significant correlation between age at onset of HD and
      length of the CAG repeat, as well as clinical disability and age at onset. The
      degree of basal ganglia atrophy correlated with the length of the CAG repeat.
      There was no correlation between cerebellar or cerebral volume and length of the
      CAG repeat. However, there was a tendency to a positive correlation between
      duration of disease and cerebellar atrophy. While there was a negative
      correlation of length of the CAG repeat with age at disease onset and with
      striatal degeneration, its influence on extrastriatal atrophy, including the
      cerebellum, was not clear. Extrastriatal atrophy occurs later in HD and may be
      related to disease duration.

PMID- 16906289
TI  - Obese obstructive sleep apnea patients with tonsil hypertrophy submitted to
      tonsillectomy.
AB  - The physiopathology of obstructive sleep apnea-hypopnea syndrome (OSAHS) is
      multifactorial and obesity has been shown to be one of the main factors
      correlated with its occurrence. In obese patients with anatomical alterations of
      the upper airways it is often difficult to predict success for surgical
      correction since obesity is a limiting factor. Therefore, the aim of the present
      study was to evaluate the results of tonsillectomy in a specific group of
      patients, i.e., obese OSAHS patients with tonsil hypertrophy. Seven OSAHS
      patients with moderate obesity with obstructive palatine tonsil hypertrophy were
      submitted to tonsillectomy. All patients were submitted to pre- and postoperative
      appraisal of body mass index, otorhinolaryngology examination and
      polysomnography. Patients' average age was 36.4 +/- 10.3 years and average
      preoperative body mass index was 36.6 +/- 6.3 kg/m(2). Postoperative weight did
      not differ significantly from preoperative weight (P = 0.27). Average
      preoperative apnea and hypopnea index (AHI) was 81 +/- 26/h and postoperative AHI
      was 23 +/- 18/h (P = 0.0005). Average preoperative minimum oxyhemoglobin
      saturation (SaO2 min) was 69 +/- 14% and the postoperative value was 83 +/- 3% (P
      = 0.038). In relation to AHI, 6 (86%) of the 7 patients studied showed a
      reduction of 50% in relation to preoperative level and of these, 4 (57%)
      presented AHI of less than 20%. Only one patient presented a reduction of less
      than 50% in AHI, but even so showed improved SaO2 min. Tonsillectomy treatment
      for OSAHS in obese patients with obstructive palatine tonsil hypertrophy caused a
      significant reduction in AHI, with improvement in SaO2 min. This procedure could
      be eventually considered as an option of treatment for obese OSAHS patients with
      significant tonsil hypertrophy when continuous positive air pressure therapy is
      not possible as the first choice of treatment.

PMID- 16906290
TI  - Hydrologic cycle and dynamics of aquatic macrophytes in two intermittent rivers
      of the semi-arid region of Brazil.
AB  - The dynamics of aquatic macrophytes in intermittent rivers is generally related
      to the characteristics of the resistance and resilience of plants to hydrologic
      disturbances of flood and drought. In the semi-arid region of Brazil,
      intermittent rivers and streams are affected by disturbances with variable
      intensity, frequency, and duration throughout their hydrologic cycles. The aim of
      the present study is to determine the occurrence and variation of biomass of
      aquatic macrophyte species in two intermittent rivers of distinct hydrologic
      regimes. Their dynamics were determined with respect to resistance and resilience
      responses of macrophytes to flood and drought events by estimating the variation
      of biomass and productivity throughout two hydrologic cycles. Twenty-one visits
      were undertaken in the rewetting, drying, and drought phases in a permanent
      puddle in the Avelos stream and two temporary puddles in the Taperoa river, state
      of Paraiba, Northeast Brazil. The sampling was carried out by using the square
      method. Floods of different magnitudes occurred during the present study in the
      river and in the stream. The results showed that floods and droughts are
      determining factors in the occurrence of macrophytes and in the structure of
      their aquatic communities. The species richness of the aquatic macrophyte
      communities was lower in the puddles of the river and stream subject to flood
      events, when compared to areas where the run-off water is retained. At the
      beginning of the recolonization process, the intensity of the floods was decisive
      in the productivity and biomass of the aquatic macrophytes in the Taperoa river
      and the Avelos stream. In intermediate levels of disturbance, the largest values
      of productivity and biomass and the shortest time for starting the recolonization
      process occurred.

PMID- 16906291
TI  - Twenty years of post-fire plant succession in a "cerrado", Sao Carlos, SP,
      Brazil.
AB  - Secondary succession in degraded areas is little studied, especially where long
      term observation of evolutionary processes is concerned. The aim of this work was
      to follow the qualitative and quantitative changes in vegetation throughout the
      regeneration process after fire in a cerrado with forest physionomy. The area
      under study is a reserve on CPPSE-EMBRAPA's farm, Sao Carlos region of Sao Paulo
      State, Brazil. In 1981, an especially destructive fire eliminated the aerial part
      of the vegetation and litter. From that time, the vegetation in three permanent
      quadrats of 2 x 20 m was recorded for twenty years. The results demonstrated the
      rapid growth of herbs, shrubs, climbers and trees successively, with a great
      species richness and, after a certain time, a decline in density at a rate
      similar to the initial recovery. Both the soil seed bank and sprouting
      subterranean organs played important parts in the recovery of the vegetation.
      Three phases were observed in the plant succession: plant growth, followed by
      intraspecific competition with a reduction in the number of individuals and
      finally interspecific competition with the disappearance of some species from the
      quadrats. The different populations behaved similarly and the rise and fall in
      density of each species over time reflected their ecological role.

PMID- 16906292
TI  - Effect of local mate competition on fig wasp sex ratios.
AB  - In fig wasps, mating takes place among the offspring of one or a few foundress
      mothers inside the fig from which mated females disperse to found new broods.
      Under these conditions, related males will compete with each other for mating and
      several studies have shown female bias in brood sex ratios as a response to Local
      Mate Competition (LMC). Studying Pegoscapus tonduzi which pollinates Ficus
      citrifolia in Brazil, we analysed the effect of LMC (number of foundresses) on
      the sex ratio of the offspring of pollinating wasps. The relationship between the
      foundress number and brood sex ratio qualitatively followed the theory, however
      the empirical sex ratio was more female biased than expected from theoretical
      values. The model for an optimal sex ratio considers that each foundress wasp
      contributes the same number of eggs to be bred and that the violation of this
      assumption may explain the lack of adjustment in relation to the theory.

PMID- 16906293
TI  - Ephemeroptera, Plecoptera and Trichoptera assemblages from riffles in mountain
      streams of Central Brazil: environmental factors influencing the distribution and
      abundance of immatures.
AB  - The influence of environmental factors on the distribution of Ephemeroptera,
      Plecoptera and Trichoptera (EPT) immatures was investigated in streams of the
      Brazilian Center-West (Serra do Pireneus, Pirenopolis, State of Goias). The
      insects were sampled by lifting the stones in front of a sieve (0.5 mm mesh) and
      then removing the insects from both the stone and the sieve. Sampling was carried
      out for 1 h at 5 collection sites over a period of 14 months. Air and water
      temperature (degrees C), water velocity (m/s), discharge (m(3)/s), electric
      conductivity (microS/cm), pH, and rainfall (mm) were also recorded. In general,
      we may state that altitude, hydrologic classification (order) and vegetation
      cover were the most important factors explaining the distribution of
      Ephemeroptera, Plecoptera and Trichoptera immatures. The influence of the
      rainfall on the temporal variation of the abundance of insects was stronger in
      stream segments of medium order (3rd, 4th order) compared to smaller streams
      (first order).

PMID- 16906294
TI  - Spatial and temporal distribution of benthic macroinvertebrates in a Southeastern
      Brazilian river.
AB  - Benthic macroinvertebrate assemblages are structured according to physical and
      chemical parameters that define microhabitats, including food supply, shelter to
      escape predators, and other biological parameters that influence reproductive
      success. The aim of this study is to investigate spatial and temporal
      distribution of macroinvertebrate assemblages at the Macae river basin, in Rio de
      Janeiro state, Southeastern Brazil. According to the "Habitat Assessment Field
      Data Sheet--High Gradient Streams" (Barbour et al., 1999), the five sampling
      sites are considered as a reference condition. Despite the differences in
      hydrological parameters (mean width, depth and discharge) among sites, the
      physicochemical parameters and functional feeding groups' general structure were
      similar, except for the less impacted area, which showed more shredders.
      According to the Detrended Correspondence Analysis based on substrates, there is
      a clear distinction between pool and riffle assemblages. In fact, the riffle
      litter substrate had higher taxa in terms of richness and abundance, but the pool
      litter substrate had the greatest number of exclusive taxa. A Cluster Analysis
      based on sampling sites data showed that temporal variation was the main factor
      in structuring macroinvertebrate assemblages in the studied habitats.

PMID- 16906295
TI  - Dimethoate 40% organosphosphorous pesticide toxicity in Prochilodus lineatus
      (Prochilodontidae, Characiformes) eggs and larvae.
AB  - Toxicity tests using early life stages of fish are of great importance in
      assessing risks to growth, reproduction and survival in polluted environments and
      are important tools for good environmental monitoring. However, a small number of
      standard bioassays of this type have been developed in Brazil. Curimbata
      (Prochilodus lineatus) is an abundant South American characid fish of great
      commercial interest. It was chosen for testing different concentrations of 40%
      dimethoate, an organophosphate insecticide and acetylcholinesterase enzyme (AChE)
      inhibitor used widely in Brazil. The 48-h LC50 for eggs is higher than 16.0
      microg.L-1, whereas for recently hatched larvae it was found to be significantly
      lower (11.81 microg.L-1, ranging between 10.23 microg.L-1 - 13.65 microg.L-1) and
      also significantly lower than that for eggs by a Student t-test for independent
      samples (p = 0.03). The 96-h LC50 for 3-day old larvae was 10.44 microg.L-1 (8.03
      microg.L-1 - 13.57 microg.L-1), similar to that of recently-hatched larvae (p =
      0.76). Larval mobility was also found to be reduced by this insecticide.

PMID- 16906296
TI  - The effect of the size of particles on mineralization of Oxycaryum cubense
      (Poepp. & Kunth) Lye.
AB  - Assays were carried out to evaluate effects of detritus size on the
      mineralization of an aquatic macrophyte, the Oxycaryum cubense. Samples of plant
      and water were collected from an oxbow lake, the Infernao lagoon (21 degrees 35'
      S and 47 degrees 51' W) located at Mogi Guacu river floodplain. The plants were
      taken to the laboratory, washed under tap water, dried (50 degrees C) and
      fractioned into six groups according to their size, viz. 100, 10, 1.13, 0.78,
      0.61 and 0.25 mm. Decomposition chambers were prepared by adding 1.0 g of plant
      fragments to 4.1 L of water lagoon. In sequence, the incubations were aerated and
      the concentrations of dissolved oxygen, the pH, the electric conductivity and the
      temperature were monitored for 120 days. The occurrence of anaerobic processes
      was avoided by reoxygenating the solutions. The experimental results were fitted
      to a first order kinetic model and the consumption of dissolved oxygen from
      mineralization processes was obtained. The physical process of fragmentation of
      O. cubense detritus is unlikely to promote the consumption of higher quantities
      of dissolved oxygen in mineralization processes meaning that fragmentation should
      not interfere in the balance of DO in this aquatic system, however fragmentation
      processes favored the acidification and increased the liberation of dissolved
      ions from the Infernao lagoon.

PMID- 16906297
TI  - Migration of the curimbata Prochilodus lineatus (Valenciennes, 1836) (Pisces,
      Prochilodontidae) at the waterfall "Cachoeira de Emas" of the Mogi-Guacu river-
      Sao Paulo, Brazil.
AB  - In this paper, we counted the ascending curimbatas at the fish ladder at the
      Cachoeira de Emas from October, 1992 to September, 1993 in one whole day (24 h
      period) per month at different observation points in the dam for 5 min every
      hour. Most of the fish (80%) were counted not in the fish ladder itself, but in
      two adjacent spillways at its left, perhaps due to the comparatively increased
      flow as they are narrower than the ladder. The bulk of the migration occurred in
      September/October. We inspected the degree of injury of the fish in order to
      examine the hypothesis that larger fish are less injured, however no conclusion
      was reached. The degree of injury varied between different points and in
      different months of the year.

PMID- 16906298
TI  - Soil characteristics of a hyperseasonal cerrado compared to a seasonal cerrado
      and a floodplain grassland: implications for plant community structure.
AB  - Savannas may be divided according to their seasonality into semi-seasonal,
      seasonal, hyperseasonal, or marshy savannas. Hyperseasonal savannas are
      characterized by the alternation of two contrasting stresses during each annual
      cycle, one induced by drought and fire and the other, by waterlogging. In South
      America, the largest savanna region is the Brazilian cerrado, in which there are
      few hyperseasonal areas that become waterlogged in the rainy season. The cerrado
      soils are generally well drained, but in central Brazil there is a small cerrado
      area in which the soil is poorly drained and which becomes waterlogged in the
      middle of the rainy season, allowing the appearance of a hyperseasonal cerrado.
      As long as soil is important in the ecology of the cerrado vegetation, we asked
      whether the waterlogging in this hyperseasonal cerrado implied that there were
      differences in soil characteristics in relation to a seasonal cerrado, which is
      not waterlogged in the rainy season, and to a floodplain grassland, which remains
      waterlogged throughout the year. In each environment, we randomly selected ten
      points, in which we collected soil samples in the mid-rainy season for chemical
      and granulometric analyses. For all variables, we found significant differences
      among the three environments, at least at one of the depths. Nevertheless, when
      we took into account all the variables together, we observed that the soils under
      the hyperseasonal and seasonal cerrados were similar and both were different to
      the soil under the floodplain grassland. The soil under the floodplain grassland
      was related to larger amounts of clay, silt, organic matter, phosphorus,
      aluminium, aluminium saturation, cation exchange capacity, and sum of bases,
      whereas soils under hyperseasonal and seasonal cerrados were related to higher pH
      values, base saturation, calcium, magnesium, and sand. As long as the soil under
      both cerrados was chemically and physically similar, the duration of waterlogging
      in the hyperseasonal cerrado is not long enough to alter its soil
      characteristics. Limitations to the plants growing on the hyperseasonal cerrado
      soil must be a consequence of the direct effects of flooding. Since cerrado plant
      species are dryland ones, the hypoxia caused by waterlogging may limit the number
      of cerrado species able to withstand these conditions.

PMID- 16906299
TI  - Insect folivory in Didymopanax vinosum (Apiaceae) in a vegetation mosaic of
      Brazilian cerrado.
AB  - Susceptibility of Didymopanax vinosum (Apiaceae) to insect herbivores was
      investigated in three sites of a cerrado mosaic--composed of campo cerrado (a
      grassland with scattered trees and shrubs), cerradao (a tall woodland) and
      cerrado sensu stricto (intermediate between the two)--situated in Cerrado Pe-de
      Gigante, Santa Rita do Passa Quatro, SP, Brazil. We also examined the
      relationship of folivory with the composition and abundance of the insect
      herbivore fauna, and with several nutritional and defensive plant characteristics
      (water, nitrogen, cellulose, lignin, tannin leaf contents, and leaf toughness).
      We collected insects associated with D. vinosum every month, and we measured leaf
      damage every three months. In general, the annual folivory differed among sites.
      It reached the highest rates in site 1 and site 3: 7.33 and 8.5 percent,
      respectively. Only 1.32 percent of annual folivory was observed in site 2. These
      levels resulted from the higher abundance, in sites 1 and 3, of the thrips
      Liothrips didymopanacis (Phlaeothripidae), the most abundant herbivore sampled,
      responsible for more than 90 percent of the observed damage. However, no
      significant relationship was found between insect activity and the chemical and
      physical composition of the leaves. Our findings suggest that, at least in this
      species, other chemical compounds or variables related to plant apparency and
      resource availability to herbivores (e.g. plant architecture) might play a more
      decisive role in the spatial variation of folivory than the nutritional and
      defensive traits that were analyzed.

PMID- 16906300
TI  - Stream fish, water and habitat quality in a pasture dominated basin, southeastern
      Brazil.
AB  - A fish survey in 35 stream reaches (from 1st to 3rd order) with physicochemical
      and habitat assessment in the Sao Jose dos Dourados system, southeastern Brazil,
      was conducted. Most of the basin land cover (77.4%) is used for pasture. From the
      sampled stream reaches, 24 were of good physicochemical quality, 10 of fair
      quality, and only one of poor quality. A habitat assessment showed that 10 stream
      reaches were considered fair, 22 were poor, and 3 were very poor. Fifty species
      were collected and their abundances showed strong correlation with habitat
      descriptors. In addition to the correlation between fish abundance and habitat,
      some species also showed optimal distribution related to the degree of physical
      habitat conservation. Streams located in this region experience organic
      pollution, but the most important aspect is the decline of the instream physical
      habitat condition, especially in first order streams, which negatively affects
      coarse substrates and water column dependent fish species. Effluent control,
      riparian vegetation restoration programs, siltation control and adequate
      sustainable soil use are practices which could mitigate such impacts.

PMID- 16906301
TI  - Spawning and parental care in Hoplias malabaricus (Teleostei, Characiformes,
      Erythrinidae) in the Southern Pantanal, Brazil.
AB  - Herein we describe spawning and egg guarding in the erythrinid fish Hoplias
      malabaricus observed in the southern Pantanal (19 degrees 34' S and 57 degrees
      00' W), state of Mato Grosso do Sul, Brazil. Nests were depressions built on
      sandy soil in flooded areas, and contained a mean of 8,197 +/- 2,204 eggs (N =
      4); the mean diameter of eggs was 1.44 +/- 0.09 mm (N = 400). Among 11 nests
      observed, eight were guarded by males and three by the pair. One male remained in
      the nest for six days, and two pairs remained guarding the eggs for at least
      three days before being captured. Females (N = 2) captured in the nest contained
      oocytes in their ovaries. Our observations suggest that male parental care is the
      normal form of parental care in H. malabaricus, but biparental care also seems to
      occur.

PMID- 16906302
TI  - Phylogenetic approach to the study of Triatomines (Triatominae, Heteroptera).
AB  - Triatomines are insects belonging to the Hemiptera order, Heteroptera suborder,
      Reduviidae family and Triatominae subfamily. All members of this subfamily are
      hematophagous. Triatomines evolved from Reduviidae predators and they are
      probably polyphyletic in origin. The combination of anatomical, physiological and
      ethological factors observed in this group, as well as the plesiomorphic and
      apomorphic characters that differentiate the five tribes and fourteen triatomine
      genera reinforce the polyphiletic hypotesis. However if we consider the five
      groups of triatomines, the Rhodniini, Cavernicolini, Bolboderini, Linshcosteini
      and Alberproseniini tribes constitute monophyletic groups, while the Triatomini
      tribe is considered polyphyletic. The New World is the center of triatomine
      diversity and seems to be the point of group origin. Of approximately 137
      triatomine species, 105 are only found in the Americas. It is now considered that
      triatomines represent a polyphyletic group defined according to their convergent
      apomorphic hematophagous characters, which have appeared several times in
      Reduviidae. This study revises the phylogeny of these vectors of Chagas' disease,
      covering such topics as the origin of hematophagy in triatomines and ancestral
      proposal for the group.

PMID- 16906303
TI  - Storage in cerrado soil and germination of Psychotria vellosiana (Rubiaceae)
      seeds.
AB  - The regeneration of plant communities from seed depends, to a large extent, on
      the capacity of the seed remaining viable in the soil. The viability and
      germination of artificially buried Psychotria vellosiana seeds in cerrado soil
      were studied, with the purpose of discovering some physio-ecological aspects of
      dispersed seeds and evaluating their potential to constitute a soil seed bank.
      Seed samples were placed in nylon envelopes and buried in the soil of a Cerrado
      reserve at two different depths and sites. Buried seeds were retrieved
      periodically and tested for germination along with dry-stored seeds. In general,
      there was a reduction in seed germination with storage time, both in soil and dry
      stored conditions, and in some assays exhumed seeds germinated faster than dry
      stored ones. In general the soil storage favoured seed viability of ungerminated
      seeds as compared to dry stored ones, with the seeds remaining partially viable
      after 10 months of storage. The lack of germination of viable seeds suggests that
      seeds showed true dormancy and/or required an extended time to germinate. It was
      observed that some seeds had germinated while buried and such in situ germination
      tended to increase with rainfall. The water availability in the soil might be a
      limiting factor for successful germination of P. vellosiana in the field, and the
      seeds may constitute a persistent soil seed bank in the cerrado as dispersed
      seeds remain viable in the soil until the following period of seed dispersal.

PMID- 16906304
TI  - The Drosophila community in xerophytic vegetations of the upper Parana-Paraguay
      river basin.
AB  - The genus Drosophila is the most abundant in the Drosophilidae family. Some
      species are endemic to certain regions and others are cosmopolitans. In Brazil,
      there are several ecosystems to explore regarding the composition and ecological
      aspects of Drosophila. Xerophytic areas are an example. They can be found in the
      South and Southeast of Brazil as islands, a result of paleoclimatic cycle
      changes. The aim of the present work is to provide information about the
      composition of the Drosophila community in eight xerophytic areas (where the
      cactus Cereus hildmaniannus occurs) in the South and Southeast of Brazil. This
      work is an important step in the study of quantitative ecological aspects of the
      Drosophila community in xerophytic areas that form continental islands in the
      Neotropical region. The composition of the Drosophila community which was found
      is compatible with previous work in several aspects. The ecological indexes
      showed a possible positive association between diversity and the degree of
      preservation of the studied areas. Sao Paulo state communities presented the
      highest similarity among the sites tested, although no statistical significant
      correlation between the Jaccard index and geographical distance was found using
      the Mantel test.

PMID- 16906305
TI  - Flight activity of Melipona asilvai Moure (Hymenoptera: Apidae).
AB  - Many stingless bee species are specific to their areas of occurrence. Even when
      adapted to their local climate and flora conditions, they are subject to
      modifications in the environment, directly influencing flight activity. The aim
      of this work is to obtain information about the flight activity of the stingless
      bee Melipona asilvai Moure, thus contributing to the knowledge of this species.
      The flow of bees entering and leaving the colony was evaluated, and the type of
      transported material was identified. This information was correlated with
      climatic data collected at the time of observations, performed between June 2002
      and March 2003. It can be proved that temperature was the factor with the
      greatest influence on the external activity of this species, showing a
      significant positive correlation with the entry of bees into the colony and
      pollen collection. Mud collecting showed a significant positive correlation with
      a humidity increase. Flight activity began at a temperature of 21.0 degrees C and
      humidity of 84.5%, peaking at 27.4 degrees C and 60.6% RH, respectively.

PMID- 16906307
TI  - Effect of nectar secretion rate on pollination success of Passiflora coccinea
      (Passifloraceae) in the Central Amazon.
AB  - The pollination of Passiflora coccinea by the hummingbird Phaethornis
      superciliosus was studied in Central Amazon, Brazil. We hypothesized that a
      greater nectar secretion rate (NSR) increases the pollination success of single
      flowers through Ph. superciliosus visiting behavior. For control flowers, NSR was
      an increasing function of flower base diameter (FBD). The total number of Ph.
      superciliosus probes per flower was an increasing function of FBD. Additionally,
      deposition of pollen on stigmas increased with the cumulative number of Ph.
      superciliosus probes. Our results show that larger P. coccinea flowers secrete
      nectar at higher rates, are probed more times during each hummingbird visit and
      are more successful at pollination. This seems to be the first non-manipulative
      study describing such an effect of NSR on the pollination of single flowers in
      nature.

PMID- 16906306
TI  - Changes in soluble carbohydrates during storage of Caesalpinia echinata LAM.
      (Brazilwood) seeds, an endangered leguminous tree from the Brazilian Atlantic
      Forest.
AB  - Caesalpinia echinata seeds stored in laboratory environmental conditions lose
      their viability in one month whilst under low temperatures germination is
      maintained for 18 months of storage. These seeds are tolerant to desiccation,
      keeping their viability up to 0.08 gH2O.gDW-1. Since soluble carbohydrates are
      believed to be involved with desiccation tolerance and seed storability, the aim
      of this work is to analyze the content and composition of soluble carbohydrates
      in C. echinata seeds during storage in paper bags (PB) and glass flasks (GF) at
      laboratory room (RT) and cool (CT) temperatures. In freshly harvested seeds,
      total soluble carbohydrates comprised approximately 10% of the dry weight,
      decreasing to ca. 8% over 18 months of storage at RT. In seeds stored at CT,
      sugars varied differently decreasing initially and being restored at the end of
      the analysis period. The main neutral sugars in seeds from all treatments were
      sucrose, fructose and glucose. Raffinose and stachyose were present as traces.
      Free myo-inositol and other cyclitols were also detected. The main tendency
      observed was the variation in levels of both glucose and fructose in relation to
      sucrose, the highest levels of monosaccharides which were found in seeds stored
      at CT. The values of glucose and fructose were practically constant in seeds
      stored in paper bags for 18 months at CT, decreasing consistently in the other
      treatments, mainly at RT. Sucrose contents remained relatively stable. Changes in
      soluble sugars during storage suggest that the loss of germinability of seeds of
      C. echinata could be associated with low levels of glucose and fructose in
      relation to sucrose.

PMID- 16906308
TI  - Aiura, a new genus of Campopleginae (Hymenoptera; Ichneumonidae) from Brazil.
AB  - Aiura, a new genus of Campopleginae (Hymenoptera; Ichneumonidae) and the species
      A. miri and A. turu are described from Campos do Jordao, SP, Brazil.

PMID- 16906309
TI  - Morphology and anatomy of a leaf mine in Vismia guianensis (Aubl.) Choisy
      (Clusiaceae) in a fragment of Brazilian Atlantic forest.
AB  - Mines or hyponomes are channels caused by larva miners consuming internal plant
      tissues. These miners live on the leaf and feed from these tissues. Leaf mines
      are usually visible on the exterior of the leaf as serpentine paths, blotches, or
      other characteristic shapes of discolored tissues. Morphological and structural
      modifications undergone by mined leaves of Vismia guianensis (Aubl.) Choisy are
      presented here with the purpose of elucidating their structure and to contribute
      to studies about insect-plant interactions. Healthy and mined leaves were
      harvested from thirty plants and taken to the laboratory. For each branch, the
      total number of young and mature leaves, the number of leaves with mines and the
      number of mine per leaf were counted. Transverse sections of healthy and mined
      leaves were obtained to observe the morpho-anatomic aspects. From the 1,438
      mature leaves and 379 young leaves analyzed, 214 (14.9%) and 70 (18.5%) were
      mined, where most of the leaves (67%) presented one mine per leaf. Transverse
      sections of the mine revealed that the larva consumed only mesophyll parenchyma
      tissue and the epidermis remains intact. There is not a pattern of leaf mining,
      but the larvae did not consume the druses observed on mesophyll and the vascular
      tissues of the mid-vein and lateral vein.

PMID- 16906310
TI  - [Prevalence of violence against women users of health services].
AB  - OBJECTIVE: Intimate partner abuse is a complex phenomenon and a public health
      problem and health care services are one of the places sought by women in this
      situation. The objective of this study was to assess the prevalence of violence
      against women attending a health care center. METHODS: This study was carried out
      in a municipality of Southeastern Brazil, in 2003. A sample of 265 women, aged 18
      to 49 years old, was interviewed using a questionnaire administered face-to-face.
      Violence was classified as psychological, physical, sexual and general.
      Statistical analyses utilized were exact logistic regression and Fisher's exact
      test. RESULTS: Psychological violence, at least once in life, was reported by
      41.5%, physical violence by 26.4%, and 9.8% reported sexual violence. "General
      violence", which refers to anyone of the above mentioned types of violence, was
      reported by 45.3% of the women, and, in 20.3% of the cases, they stated it had
      occurred during the last 12 months before the interview. However, when asked
      whether they had suffered any kind of violence in life, only 22.3% answered
      affirmatively. The multivariate analysis indicated that the risk factors for each
      type of violence were: drug use by the partner, socioeconomic status and family
      history of violence for both psychological and general violence; drug use by the
      partner, schooling and family history of violence for physical violence; and,
      socioeconomic status and family history of violence for sexual violence.
      CONCLUSIONS: This study indicates that the prevalence of violence among women
      attending the health center is high and consistent with the results of other
      investigations. It also suggests that most of the violence is invisible to the
      health center.

PMID- 16906311
TI  - [Use of condoms during sexual intercourse: a population-based study].
AB  - OBJECTIVE: To describe characteristics associated with failure to use condoms
      during sexual intercourse by women. METHODS: We conducted a cross-sectional
      population-based study including 1,026 women aged 20-60 years living in the urban
      area of a city in Southern Brazil, in 2003. Cluster sampling was carried out by
      randomly selecting 40 of the city's 270 census sectors. We performed logistic
      regression analysis of failure to use condoms in relation to socioeconomic,
      demographic, obstetric, and health care usage variables. RESULTS: Among studied
      women, 867 (84.5%) reported being sexually active; of these, 252 (29.1%) wore
      condoms during sexual intercourse. Logistic regression showed that the most
      vulnerable groups were women who were married or in stable partnerships, and
      women aged more than 40 years. We found no associations with the other variables
      explored. CONCLUSIONS: Prevalence of condom use was low; we were able to identify
      a group of women that needs to be targeted by health policies and services in
      order to improve perception of the risk of acquiring sexually transmitted
      diseases.

PMID- 16906312
TI  - [Mini-Mental State Examination: psychometric characteristics in elderly
      outpatients].
AB  - OBJECTIVE: To assess the psychometric characteristics of the Mini-Mental State
      Examination in elderly outpatients who seek primary health care. METHODS: A total
      of 303 subjects (>65 years) underwent comprehensive geriatric assessment with
      functional tools, including Mini-Mental State Examination. Sensitivity,
      specificity, positive predictive value, negative predictive value, and ROC curve
      were calculated. RESULTS: Sensitivity, specificity, positive and negative
      predictive values, and area under ROC curve were 80.8%, 65.3%, 44.7%, 90.7% and
      0.807 respectively (cutoff point =23/24). The best cutoff point for illiterate
      was 18/19 (sensitivity =73.5%; specificity =73.9%); and for literate was 24/25
      (sensitivity =75%; specificity =69.7%). CONCLUSIONS: While screening elderly
      outpatients for dementia, schooling must be considered in the choice of the best
      cutoff point in the Mini-Mental State Examination.

PMID- 16906313
TI  - [Prevalence and factors associated to overweight and obesity in adolescents].
AB  - OBJECTIVE: To assess the prevalence and factors associated to overweight and
      obesity in urban area adolescents. METHODS: A cross-sectional population-based
      study was carried out in the municipality of Pelotas, Southern Brazil, between
      2001 and 2002. Adolescents between 15 and 18 years old were weighed, measured and
      asked to complete a self-administered questionnaire. Of 90 areas drawn, 86
      dwellings were visited in each area, comprising a total of 960 adolescents
      interviewed. Overweight and obesity prevalences were defined based on the body
      mass index, according to cutoff values and adjusted to age and sex. Multivariate
      analysis with Poisson regression was performed using a hierarchical model of
      variables associated to overweight and obesity. RESULTS: Overweight and obesity
      prevalences were 20.94% and 5% respectively. There was found an inverse
      relationship between obesity and age and schooling. An association of overweight
      and obesity with reporting parents' obesity (p=0.03) and adolescents' sexual
      maturation (p=0.01) was seen. Dieting and skipping meals were associated to
      obesity with a risk of 3.98 (95% CI: 1.83-8.67) and 2.54 (95% CI: 1.22-5.29)
      respectively. CONCLUSIONS: Overweight and obesity prevalences in the area studied
      are of concern despite adolescents' behaviors to prevent to obesity. There is a
      need to implement more effective campaigns to provide better guidance to
      adolescents.

PMID- 16906314
TI  - Relative frequency, clinical, neuroimaging, and postsurgical features of
      pediatric temporal lobe epilepsy.
AB  - We describe the relative frequency, clinical features, neuroimaging and
      pathological results, and outcome after pharmacological or surgical intervention
      for a series of pediatric patients with temporal lobe epilepsy (TLE) from an
      epilepsy center in Brazil. The medical records of children younger than 12 years
      with features strongly suggestive of TLE were reviewed from January 1999 to June
      1999. Selected children were evaluated regarding clinical, EEG, and magnetic
      resonance imaging (MRI) investigation and divided into three groups according to
      MRI: group 1 (G1, N = 9), patients with hippocampal atrophy; group 2 (G2, N =
      10), patients with normal MRI, and group 3 (G3, N = 12), patients with other
      specific temporal lesions. A review of 1732 records of children with epilepsy
      revealed 31 cases with TLE (relative frequency of 1.79%). However, when the
      investigation was narrowed to cases with intractable seizures that needed video
      EEG monitoring (N = 68) or epilepsy surgery (N = 32), the relative frequency of
      TLE increased to 19.11 (13/68) and 31.25% (10/32), respectively. At the beginning
      of the study, 25 of 31 patients had a high seizure frequency (80.6%), which
      declined to 11 of 31 (35.5%) at the conclusion of the study, as a consequence of
      pharmacological and/or surgical therapy. This improvement in seizure control was
      significant in G1 (P < 0.05) and G3 (P < 0.01) mainly due to good postsurgical
      outcome, and was not significant in G2 (P > 0.1, McNemar's test). These results
      indicate that the relative frequency of TLE in children was low, but increased
      considerably among cases with pharmacoresistant seizures. Patients with specific
      lesions were likely to undergo surgery, with good postoperative outcomes.

PMID- 16906320
TI  - The clinical impact of MTHFR polymorphism on the vascular complications of sickle
      cell disease.
AB  - Sickle cell disease (SCD) is one of the most common inherited diseases in the
      world and the patients present notorious clinical heterogeneity. It is known that
      patients with SCD present activation of the blood coagulation and fibrinolytic
      systems, especially during vaso-occlusive crises, but also during the steady
      state of the disease. We determined if the presence of the factor V gene G1691A
      mutation (factor V Leiden), the prothrombin gene G20210A variant, and
      methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism may be risk
      factors for vascular complications in individuals with SCD. We studied 53
      patients with SCD (60% being women), 29 with SS (sickle cell anemia; 28 years,
      range: 13-52 years) and 24 with SC (sickle-hemoglobin C disease; 38.5 years,
      range: 17-72 years) hemoglobinopathy. Factor V Leiden, MTHFR C677T polymorphism,
      and prothrombin G20210A variant were identified by PCR followed by further
      digestion of the PCR product with specific endonucleases. The following vascular
      complications were recorded: stroke, retinopathy, acute thoracic syndrome, and X
      ray-documented avascular necrosis. Only one patient was heterozygous for factor V
      Leiden (1.8%) and there was no prothrombin G20210A variant. MTHFR 677TT
      polymorphism was detected in 1 patient (1.8%) and the heterozygous form 677TC was
      observed in 18 patients (34%, 9 with SS and 9 with SC disease), a prevalence
      similar to that reported by others. No association was detected between the
      presence of the MTHFR 677T allele and other genetic modulation factors, such as
      alpha-thalassemia, beta-globin gene haplotype and fetal hemoglobin. The presence
      of the MTHFR 677T allele was associated with the occurrence of vascular
      complications in SCD, although this association was not significant when each
      complication was considered separately. In conclusion, MTHFR C677T polymorphism
      might be a risk factor for vascular complications in SCD.

PMID- 16906322
TI  - Incidence, risk factors and prognostic factors of acute renal failure in patients
      admitted to an intensive care unit.
AB  - The objective of the present study was to assess the incidence, risk factors and
      outcome of patients who develop acute renal failure (ARF) in intensive care
      units. In this prospective observational study, 221 patients with a 48-h minimum
      stay, 18-year-old minimum age and absence of overt acute or chronic renal failure
      were included. Exclusion criteria were organ donors and renal transplantation
      patients. ARF was defined as a creatinine level above 1.5 mg/dL. Statistics were
      performed using Pearsons' chi2 test, Student t-test, and Wilcoxon test.
      Multivariate analysis was run using all variables with P < 0.1 in the univariate
      analysis. ARF developed in 19.0% of the patients, with 76.19% resulting in death.
      Main risk factors (univariate analysis) were: higher intra-operative hydration
      and bleeding, higher death risk by APACHE II score, logist organ dysfunction
      system on the first day, mechanical ventilation, shock due to systemic
      inflammatory response syndrome (SIRS)/sepsis, noradrenaline use, and plasma
      creatinine and urea levels on admission. Heart rate on admission (OR = 1.023
      (1.002-1.044)), male gender (OR = 4.275 (1.340-13642)), shock due to SIRS/sepsis
      (OR = 8.590 (2.710-27.229)), higher intra-operative hydration (OR = 1.002 (1.000
      1004)), and plasma urea on admission (OR = 1.012 (0.980-1044)) remained
      significant (multivariate analysis). The mortality risk factors (univariate
      analysis) were shock due to SIRS/sepsis, mechanical ventilation, blood stream
      infection, potassium and bicarbonate levels. Only potassium levels remained
      significant (P = 0.037). In conclusion, ARF has a high incidence, morbidity and
      mortality when it occurs in intensive care unit. There is a very close
      association with hemodynamic status and multiple organ dysfunction.

PMID- 16906323
TI  - Results of CHOP chemotherapy for diffuse large B-cell lymphoma.
AB  - Patients with diffuse large B-cell lymphoma treated in a University Hospital were
      studied from 1990 to 2001. Two treatment regimens were used: ProMACE-CytaBOM and
      then, from November 1996 on, the CHOP regimen. Complete remission (CR), disease
      free survival (DFS), and overall survival (OS) rates were determined. Primary
      refractory patients and relapsed patients were also assessed. A total of 111
      patients under 60 years of age were assessed and ranked according to the
      international prognostic index adjusted to age. Twenty (18%) of them were
      classified as low risk, 40 (36%) as intermediate risk, 33 (29.7%) as high
      intermediate risk, and 18 (16.3%) as high risk. Over a five-year period, OS and
      DFS rates were 71 and 59%, respectively, for all patients. For the same time
      period, OS and DFS rates were 72.8 and 61.3%, respectively, for 77 patients
      treated with CHOP chemotherapy and 71.3 and 60% for patients treated with the
      ProMACE-CytaBOM protocol. There was no significant difference in OS or DFS
      between the two groups. Eleven of 50 refractory and relapsed patients were
      consolidated with high doses of chemotherapy. Three received allogenic and 8
      autologous bone marrow transplantation. For the latter, CR was 62.5% and mean OS
      was 41.1 months. The clinical behavior, CR, DFS, and OS of the present patients
      were similar to those reported in the literature. We conclude that both the CHOP
      and ProMACE-CytaBOM protocols can be used to treat diffuse large B-cell lymphoma
      patients, although the CHOP protocol is preferable because of its lower cost and
      lower toxicity.

PMID- 16906324
TI  - Diabetes, inflammation, proinflammatory cytokines, and diabetic nephropathy.
AB  - Diabetes and its complications have become a public health problem. Diabetic
      nephropathy is the main cause of renal failure. In spite of our higher knowledge
      on this complication, the intimate mechanisms leading to the development and
      progression of renal injury are not yet fully known. Activated innate immunity
      and inflammation are relevant factors in the pathogenesis of diabetes. Moreover,
      inflammation, and more specifically proinflammatory cytokines and other molecules
      with a relevant role within the inflammatory process, may be critical factors in
      the development of microvascular diabetic complications, including nephropathy.
      This new pathogenic perspective may lead to important new therapeutic
      considerations and new therapeutic goals for the treatment of diabetic
      nephropathy.

PMID- 16906325
TI  - Treating imatinib-resistant leukemia: the next generation targeted therapies.
AB  - Imatinib (Gleevec/STI-571/CGP57148B, Novartis) is a small-molecule, tyrosine
      kinase inhibitor developed to target BCR-ABL, c-Kit, and PDGF-R. Through
      inhibition of these oncogenic kinases, imatinib is effective in the treatment of
      BCR-ABL-positive leukemia, gastrointestinal stromal tumor, and hypereosinophilic
      syndrome, respectively. However, clinical success of imatinib is hampered by
      acquired resistance that may occur through several mechanisms including kinase
      domain mutation, target amplification, and activation of alternate signaling
      pathways. Strategies to overcome resistance have included targeting BCR-ABL
      stability and downstream signaling pathways important for tumor growth.
      Additional work has shown that new BCR-ABL kinase inhibitors with increased
      potency or alternate conformation-binding properties can target imatinib
      resistance. This review focuses on the mechanisms of imatinib resistance and the
      strategies currently being developed to overcome clinical resistance.

PMID- 16906326
TI  - The bacterial microflora of fish, revised.
AB  - The results of numerous studies indicate that fish possess bacterial populations
      on or in their skin, gills, digestive tract, and light-emitting organs. In
      addition, the internal organs (kidney, liver, and spleen) of healthy fish may
      contain bacteria, but there is debate about whether or not muscle is actually
      sterile. Using traditional culture-dependent techniques, the numbers and
      taxonomic composition of the bacterial populations generally reflect those of the
      surrounding water. More modern culture-independent approaches have permitted the
      recognition of previously uncultured bacteria. The role of the organisms includes
      the ability to degrade complex molecules (therefore exercising a potential
      benefit in nutrition), to produce vitamins and polymers, and to be responsible
      for the emission of light by the light-emitting organs of deep-sea fish. Taxa,
      including Pseudomonas, may contribute to spoilage by the production of histamines
      in fish tissue.

PMID- 16906327
TI  - Signal transduction of sphingosine-1-phosphate G protein-coupled receptors.
AB  - Sphingosine-1-phosphate (S1P) is a bioactive lipid capable of eliciting dramatic
      effects in a variety of cell types. Signaling by this molecule is by a family of
      five G protein-coupled receptors named S1P1-5 that signal through a variety of
      pathways to regulate cell proliferation, migration, cytoskeletal organization,
      and differentiation. These receptors are expressed in a wide variety of tissues
      and cell types, and their cellular effects contribute to important biological and
      pathological functions of S1P in many processes, including angiogenesis, vascular
      development, lymphocyte trafficking, and cancer. This review will focus on the
      current progress in the field of S1P receptor signaling and biology.

PMID- 16906328
TI  - Central histaminergic modulation of vestibular function - a review.
AB  - Histaminergic drugs have long been used to treat balance disorders in man, but
      their mechanisms of action in the vestibular system are poorly understood. In
      this article we review the current literature on histaminergic neurotransmission
      in the brain focussing particularly in the brainstem vestibular nuclei, and the
      role of histamine in brain plasticity during "vestibular compensation", the
      behavioural recovery that takes place after unilateral peripheral vestibular
      damage. Evidence that histaminergic compounds may facilitate vestibular
      compensation is reviewed, and we discuss the potential of histaminergic drugs for
      clinical use.

PMID- 16906329
TI  - Oligomeric interaction between ryanodine receptors: potential role in Ca(2+)
      release.
AB  - Receptor proteins in both eukaryotic and prokaryotic cells often form regular
      lattice or array in the membrane. Recent theoretical analyses indicate that such
      arrays may provide a novel mechanism for receptor signaling regulation in cells.
      The functional coupling between neighboring receptors could improve the signaling
      performance. The ryanodine receptors (RyR)/calcium release channels usually form
      2-D regular lattice in the endoplasmic/sarcoplasmic reticulum membranes. Thus,
      RyR is a potentially good model to study the function of receptor 2-D array. In
      this article, we briefly review recent progresses in this research field,
      including RyR-RyR interaction, RyR array's function and working mechanisms. The
      investigations performed by new methods in our laboratory are summarized. We
      demonstrate that the RyR-RyR interaction is modulated by the functional states of
      RyRs. Accordingly, the mechanism of "dynamic coupling" of RyR array is proposed.
      Its possible role in RyR-mediated Ca(2+) release is discussed.

PMID- 16906330
TI  - Immunoregulatory role of endogenous catecholamines synthesized by immune cells.
AB  - It has been well known that catecholamines (CAs) in the body, including
      norepinephrine (NE), epinephrine (E) and dopamine (DA), are synthesized and
      secreted by neurons and endocrine cells and mainly modulate visceral activities
      such as cardiovascular, respiratory and digestive functions. The studies over the
      past nearly 30 years have shown that CAs can also regulate immune function. The
      immunomodulation of CAs is generally considered as a role mediating the
      regulation of nervous and endocrine systems. However, recent studies reveal that
      immune cells can also synthesize CAs, which is an update of traditional concept.
      A classical metabolic pathway of CAs shared by the nervous and endocrine systems
      is present in the immune cells, i.e., the immunocytes have the enzymes for
      synthesis of CAs [e.g. tyrosine hydroxylase (TH)] and the enzymes for degradation
      of CAs [e.g. monoamine oxidase (MAO) and catechol-O-methyl transferase (COMT)].
      The endogenous CAs synthesized by immune cells can regulate many immune
      functions, including cellular proliferation, differentiation, apoptosis and
      cytokine production. These roles of the endogenous CAs may be mediated by an
      autocrine/paracrine pathway via relevant receptors on the immunocytes and
      intracellular cAMP. Intracellular oxidative mechanism may also be involved in
      immunoregulation of endogenous CAs in immune cells. In addition, some metabolic
      abnormalities of CAs in the immune cells probably induce some autoimmune
      diseases, such as multiple sclerosis (MS) and rheumatoid arthritis. These
      findings not only provide evidence for the new concept that the immune system is
      possible to become the third CA system other than the nervous and endocrine
      systems, but also extend our comprehension on functional significance of the
      endogenous CAs synthesized by immune cells.

PMID- 16906331
TI  - Inflammation of different tissues in spontaneously hypertensive rats.
AB  - The hypertension is one of chronic vascular diseases, which often implicates
      multiple tissues causing stroke, cardiac hypertrophy, and renal failure. A
      growing body of evidence suggests that inflammatory mechanisms are important
      participants in the pathophysiology of hypertension. In this study, the
      inflammatory status of these tissues (kidney, liver, heart, and brain) in
      spontaneously hypertensive rats (SHR) was analyzed and its molecular mechanism
      was explored. The tissues were dissected from SHR and age-matched control Wistar
      Kyoto (WKY) rats to investigate the abundance of inflammation-related mediators
      (IL-1beta, TNFalpha, ICAM-1, iNOS, C/EBPdelta and PPARgamma). mRNA levels were
      determined by reverse transcription-polymerase chain reaction and protein
      expression was evaluated by Western blot. To evaluate the oxidative stress of
      tissues, carbonyl protein content and total antioxidant capacity of tissues were
      detected by spectrophotometry and ferric reduction ability power (FRAP) method.
      The results suggest that: (1) Expressions of inflammation-related mediators (IL
      1beta, TNFalpha, ICAM-1, iNOS, C/EBPdelta and PPARgamma) in SHR were higher
      compared with those in WKY rats except no evident increase of IL-1beta mRNA in
      liver and brain in SHR. (2) Tissues in SHR contained obviously increased carbonyl
      protein (nmol/mg protein) compared to that in WKY rats (8.93+/-1.08 vs 2.27+/
      0.43 for kidney, 2.23+/-0.23 vs 0.17+/-0.02 for heart, 13.42+/-1.10 vs 5.72+/
      1.01 for brain, respectively, P<0.05). However, no evident difference in the
      amount of carbonyl protein in liver was detected between SHR and WKY rats. (3)
      Total antioxidant capacities of kidney, liver, heart and brain were markedly
      lower in SHR than that in WKY rats (P<0.05). Thus, the present data reveal a
      higher inflammatory status in the important tissues in SHR and indicate that
      inflammation might play a potential role in pathogenesis of hypertension and
      secondary organ complications.

PMID- 16906332
TI  - [Over-expression of the cellular repressor of E1A-stimulated genes inhibits the
      apoptosis of human vascular smooth muscle cells in vitro.].
AB  - To investigate the effects and molecular mechanisms of the cellular repressor of
      E1A-stimulated genes (CREG) on the apoptosis of vascular smooth muscle cells
      (VSMCs), the human internal thoracic artery-Shenyang (HITASY) cells were infected
      with sense-CREG [pLNCX(2)(+)/CREG] and antisense-CREG [pLXSN(-)/CREG] retrovirus
      respectively. The stably infected cells were obtained by screening the G418
      resistant clones. DAPI nuclei staining and Annexin V/PI FASC assay indicated that
      over-expression of CREG in HITASY cells infected with pLNCX(2) (+)/CREG inhibited
      VSMC apoptosis induced by serum deprivation, accompanied with decreased
      expression of caspase-9 mRNA detected by RT-PCR. Furthermore, Western blot
      analysis showed that p38 mitogen activated protein kinase (p38 MAPK) expression
      and activation were significantly enhanced in HITASY cells infected with pLNCX(2)
      (+)/CREG. The inhibition of CREG protein expression in cells infected with pLXSN(
      )/CREG promoted the VSMC spontaneous apoptosis, as well as down-regulated p38
      MAPK expression and activation, when cells were cultured with 10% fetal bovine
      serum (FBS) mediums. These results implicate that the CREG protein has the
      ability to regulate VSMC apoptosis in which the activation of p38 MAPK is
      possibly involved. To further identify the role of p38 MAPK in VSMC apoptosis,
      SB203580, a specific inhibitor of p38 MAPK, was used to inhibit p38 MAPK
      activity. When p38 MAPK signaling pathway was blocked, the effects that over
      expression of CREG protein inhibited VSMC apoptosis disappeared. Taken together,
      the present work indicates that over-expression of CREG protein inhibits VSMC
      apoptosis, and this inhibitory effect is partly mediated by p38 MAPK signaling
      pathway.

PMID- 16906333
TI  - [Distribution characteristic of NDRG2 expression in human fetal tissues.].
AB  - NDRG2, one of the new N-Myc downstream-regulated gene (NDRG) gene families, is
      believed to be involved in cell growth event. However, the exact function is
      still unknown. Identification of the tissue or cell types expressing this gene in
      vivo will provide clues in clarifying its physiological roles. Using RT-PCR and
      Western blot, we analyzed the expression level of NDRG2 mRNA and protein in human
      fetal tissues from different gestational ages. The anti-NDRG2 monoclonal
      antibody, which has been proved to react specifically with NDRG2 protein, was
      further used to analyze the cellular location of NDRG2 protein in various human
      fetal tissues by immunohistochemistry. We found that NDRG2 expression was
      developmentally dynamic, being generally lower in the early stages of development
      and markedly increasing during the later stages. NDRG2 mRNA and protein
      distribution were generally consistent in heart and lung. One of the differences
      was that NDRG2 protein appeared later than mRNA in kidney. Another unmatched
      expression was found in liver. NDRG2 mRNA appeared later than protein in liver.
      In human fetal tissues at sixteen and twenty-eight weeks of gestation, NDRG2
      protein immunoreactions could be seen in epithelium of small intestine,
      epithelium of large intestine, superficial layer of epidermis, whisker follicles,
      epithelium of small bronchus, hepatocytes, cardiac myocytes, thymus corpuscles
      and epithelium of renal tubule, and the immunoreactions in those tissues from
      twenty-eight weeks of gestation was stronger than that from sixteen weeks of
      gestation. In the present study, we demonstrate the expression pattern and
      cellular location of NDRG2 protein in a large set of human fetal tissues. This is
      the first demonstration of NDRG2 protein expression in human fetal tissues. Taken
      together, the results suggest that NDRG2 protein found in a variety of tissues is
      not a tissue-specific protein, and may play important roles in histogenesis and
      organogenesis.

PMID- 16906334
TI  - Gene profile for differentiation of vascular adventitial myofibroblasts.
AB  - Our previous study demonstrated that TGF-beta1 could induce the differentiation
      of vascular adventitial fibroblasts (AFs) to myofibroblasts (MFs). The aim of
      this study was to identify the genes which might be responsible for the cell
      phenotypic change using genechips. Cultured rat AFs were treated with TGF-beta1
      (10 ng/ml) for 0 min, 5 min, 15 min, 2 h, 12 h and 24 h, respectively. Then the
      cells were gathered to prepare total RNA. We examined TGF-beta1-induced gene
      expression profiling using Affymetrix oligonucleotide microarrays and analyzed
      data by GCOS1.2 software. Moreover, expressional similarity was measured by
      hierarchical clustering. Some of genechip results were confirmed by real-time
      quantitative RT-PCR. Microarray analysis identified 2121 genes with a 2-fold
      change or above after TGF-beta1 stimulation. 1318 genes showed a greater than 2
      fold increase and 761 genes were reduced 2 folds or more at mRNA levels, whereas
      a small portion of the total regulated genes (42 genes) displayed dynamically up-
      and down-regulated pattern. Genes were further segregated for early (peak at 5
      min, 15 min and/or 2 h), late (peak at 12 h and/or 24 h), and sustained (2-fold
      change or above at five time points) temporal response groups according to the
      time of their peak expression level. Among 1318 up-regulated genes, 333 genes
      (25.3%) responded rapidly to TGF-beta1 and 159 genes (12.1%) responded in a
      sustained manner. Most genes (826, 62.6%) were regulated at 12 h or later. For
      the 761 down-regulated genes, numbers of early and late responsive genes were 335
      (44%) and 267 (36.1%), respectively. There were also 159 genes, 19.9% of total
      down-regulated genes, decreased at five time points treated by TGF-beta1. The
      results suggested that the gene expressions of secreted phosphoprotein 1 (APP1)
      and Rho-associated coiled-coil forming kinase 2 (ROCK2) had the same trends as
      alpha-smooth muscle-actin, a marker of MF differentiation. In addition, the gene
      expression of potassium voltage-gated channel, Shal-related family and member 2
      (KCND2) was up-regulated. Furthermore, it was found that endothelin 1 (EDN1),
      some complement components, NADPH oxidase 4 (NOX4) and NAD(P)H dehydrogenase,
      quinone 1 (NQO1) might be involved in MF differentiation. Using microarrary
      technique, we confirmed some genes that have been identified by other techniques
      were implicated in MF differentiation and observed new genes involved in this
      process. Our results suggest that gene expression profiling study is helpful in
      identifying genes and pathways potentially involved in cell differentiation.

PMID- 16906335
TI  - Diazoxide preconditioning alleviates apoptosis of hippocampal neurons induced by
      anoxia-reoxygenation in vitro through up-regulation of Bcl-2/Bax protein ratio.
AB  - Activating mitochondrial ATP-sensitive potassium (mitoK(ATP)) channels is a
      critical event of pharmacological preconditioning, which can enhance neuronal
      ability against various insults. mitoK(ATP) channels are abundant in neurons and
      can be selectively opened by diazoxide (DZ). The aim of this study was to
      determine whether DZ could restrain neuronal apoptosis induced by anoxia
      reoxygenation and to reveal the effect of DZ preconditioning on the expressions
      of Bcl-2 and Bax proteins in cultured hippocampal neurons. Cultured for 9~10 d in
      vitro, the hippocampal neurons of Sprague-Dawley rats were assigned to the
      following 5 groups randomly: Control, DZ 0 mumol/L, DZ 30 mumol/L, DZ 100
      mumol/L, DZ 100 mumol/L+5-hydroxydecanoate (5-HD, a selective mitoK(ATP) channel
      blocker) 100 mumol/L. Prior to oxygen deprivation, the hippocampal neurons except
      those in the control group were treated with DZ or DZ+5-HD for 1 h per day and
      this treatment persisted for 3 d. Thereafter, neurons were subjected to anoxia
      for 4 h and followed by reoxygenation. At 24 h of reoxygenation the neuronal
      survival rates were measured by MTT method, while the apoptotic rates were
      assayed by annexin V-FITC staining. The expressions of Bcl-2 and Bax proteins
      were detected with immunocytochemistry and evaluated by Western blot. Anoxia
      reoxygenation injury reduced the survival rates and increased apoptotic rates
      significantly. In comparison with those in other groups, the survival rate in DZ
      100 mumol/L group was increased by about 15%, whereas the apoptotic rate was
      decreased by almost 12% simultaneously. 5-HD could abolish the neuroprotection
      afforded by 100 mumol/L DZ. Bcl-2 and Bax proteins in the control normoxic
      neurons were both expressed slightly, while anoxia-reoxygenation led to high
      expression of Bax protein. The administration of 100 mumol/L DZ enhanced the
      expression of Bcl-2 protein by nearly 60%, whereas Bax protein was reduced by
      approximately 30%. Lower concentrations of DZ had no detectable effects on the
      expressions of Bcl-2 and Bax proteins. However, beneficial effects of DZ on the
      expressions of Bcl-2 and Bax proteins were reversed after the co-treatment with 5
      HD. In conclusion, 100 mumol/L DZ prevented cultured hippocampal neurons from
      apoptosis induced by anoxia-reoxygenation possibly through up-regulating the
      expression of Bcl-2 protein and down-regulating the expression of Bax protein.

PMID- 16906336
TI  - [Effects of Nurr1 down-regulation on the expression of tyrosine hydroxylase and
      neurite extension in dopaminergic cells.].
AB  - In the experiment, we designed and synthesized two siRNAs based on the sequence
      of nuclear receptor-related factor 1 (Nurr1) mRNA. They were separately subcloned
      into the plasmid of pSilenCircle (pSC) containing U6 promoter. The pSC-Nurr1
      vectors (pSC-N1 and pSC-N2) specific to Nurr1 gene and the negative control
      vector of short-hairpin RNA (shRNA) eukaryotic expression vector were
      constructed. We cultured the dopaminergic cell line MN9D and the verified vectors
      were transfected with LipofectamineTM 2000 in vitro. The positive cell clones
      transfected with pSC were obtained after being screened with 500 mug/ml G418.
      After that, the silencing effects of Nurr1 and TH mRNA or protein were detected
      by real time RT-PCR and Western blot. The neurite extension of MN9D cells was
      observed and photographed by inverted microscope. The results showed that Nurr1
      mRNA expression in MN9D cells was specifically down-regulated by the vectors of
      pSC-N1 and pSC-N2, and the silencing effects were 62.3% and 45.6%, respectively.
      The dopaminergic phenotype of TH mRNA was also suppressed significantly and the
      silencing effects were 76.3% and 62.6%, respectively. Meanwhile, the expressions
      of Nurr1 and TH proteins were also significantly suppressed, and the silencing
      effects of Nurr1 and TH protein were 57.4%, 72.0% and 79.1%, 70.1% respectively.
      The negative control and liposome groups had no effect on the two genes. In
      conclusion, Nurr1 shRNA expressing vectors can inhibit the expressions of Nurr1
      and TH mRNA or protein in MN9D cells, and Nurr1 might play a role in neurite
      extension of MN9D cells. Nurr1 shRNA expressing vector may provide a novel
      applicable strategy for the study on the function of the genes associated with
      Parkinson disease and the development of dopaminergic neuron.

PMID- 16906337
TI  - Circadian rhythms and different photoresponses of Clock gene transcription in the
      rat suprachiasmatic nucleus and pineal gland.
AB  - The aim of this study was to observe and compare the endogenous circadian rhythm
      and photoresponse of Clock gene transcription in the suprachiasmatic nucleus
      (SCN) and pineal gland (PG) of rats. With free access to food and water in
      special darkrooms, Sprague-Dawley rats were housed under the light regime of
      constant darkness (DD) for 8 weeks (n=36) or 12 hour-light: 12 hour-dark cycle
      (LD) for 4 weeks (n=36), respectively. Then, their SCN and PG were dissected out
      every 4 h in a circadian day, 6 rats at each time (n=6). All animal treatments
      and sampling during the dark phases were conducted under red dim light (<0.1
      lux). The total RNA was extracted from each sample and the semi-quantitative RT
      PCR was used to determine the temporal mRNA changes of Clock gene in the SCN and
      PG at different circadian times (CT) or zeitgeber times (ZT). The grayness ratio
      of Clock/H3.3 bands was served as the relative estimation of Clock gene
      expression. The experimental data were analyzed by the Cosine method and the
      Clock Lab software to fit original results measured at 6 time points and to
      simulate a circadian rhythmic curve which was then examined for statistical
      difference by the amplitude F test. The main results are as follows: (1) The mRNA
      levels of Clock gene in the SCN under DD regime displayed the circadian
      oscillation (P<0.05). The endogenous rhythmic profiles of Clock gene
      transcription in the PG were similar to those in the SCN (P>0.05) throughout the
      day with the peak at the subjective night (CT15 in the SCN or CT18 in the PG) and
      the trough during the subjective day (CT3 in the SCN or CT6 in the PG). (2) Clock
      gene transcription in the SCN under LD cycle also showed the circadian
      oscillation (P<0.05), and the rhythmic profile was anti-phasic to that under DD
      condition (P<0.05). The amplitude and the mRNA level at the peak of Clock gene
      transcription in the SCN under LD were significantly increased compared with that
      under DD (P<0.05), while the value of corresponding rhythmic parameters in the PG
      under LD were remarkably decreased (P<0.05). (3) Under LD cycle, the circadian
      profiles of Clock gene transcription induced by light in the PG were quite
      different from those in the SCN (P<0.05). Their Clock transcription rhythms were
      anti-phasic, i.e., showing peaks at the light phase ZT10 in the SCN or at the
      dark time ZT17 in the PG and troughs during the dark time ZT22 in the SCN or
      during the light phase ZT5 in the PG. The findings of the present study indicate
      a synchronous endogenous nature of the Clock gene circadian transcriptions in the
      SCN and PG, and different roles of light regime in modulating the circadian
      transcriptions of Clock gene in these two central nuclei.

PMID- 16906338
TI  - [Treadmill running enhances the ability of learning in young rats.].
AB  - To investigate the effect of treadmill running on the ability of learning in
      young rats, male Sprague-Dawley rats (5 weeks of age) were used for the
      experiment. Animals were randomly divided into the control and running groups
      (n=15 in each group). The rats in running group were made run on a motor-driven
      treadmill for 1 week at a speed of 2 m/min for the first 5 min, at a speed of 5
      m/min for the next 5 min, then at a speed of 8 m/min for the last 20 min. Then
      the Morris water maze was used to observe learning and memory ability of rats in
      both groups. The tests consisted of place navigation and spatial probe test. We
      found that, in place navigation training, the latency of rats in running group
      was less than that in control group (P<0.05); and from the third training session
      on, there was significant difference between the rats in control and running
      groups in swimming velocity (P<0.01); furthermore, it was observed that the rats
      in running group had stronger motivation and more exact orientation in searching
      for platform, which could be indicated by the index of turn angle and angular
      velocity. In spatial probe test, there was no significant difference between the
      two groups in swimming velocity, percentage of swimming distance and frequency of
      crossing platform in D quadrant, where the platform situated (P>0.05). These
      findings suggest that low speed treadmill running can enhance the ability of
      learning in young rats.

PMID- 16906339
TI  - [Screening differentially expressed genes in human bone marrow stromal cells at
      defined stage of differentiation.].
AB  - To screen differentially expressed genes involved in osteogenic differentiation
      of human bone marrow stromal cells (BMSCs) at defined stages, subtractive cDNA
      library was established by means of suppression subtractive hybridization. The
      BMSCs cultured for 12 and 21 d were used as driver and tester, respectively. A
      subtract library was successfully constructed and five positive clones were
      selected from the library. Sequencing analysis and homology comparison showed
      that the five clones differentially expressed in BMSCs cultured for 21 d were at
      least 90% homologous with the known genes in human GenBank. It was interestingly
      found that the osteogenic BMSCs cultured for 21 d differentially expressed
      decorin and Bax inhibitor 1. RT-PCR was performed to confirm the differentially
      expressed genes. The results showed that the expression of Bax inhibitor 1 was
      significantly higher in the cells of 21-day than that of 12-day, while the
      expression of decorin was only detected in the cells of 21-day.

PMID- 16906340
TI  - HB-1, an acute myeloid leukemic cell line with the capability of infiltrating
      into the brain in CBA/N mice.
AB  - An acute myeloid leukemic HB-1 cell line was cloned and established from the
      spleen cells of irradiated CBA/N mice. Acute myeloma leukemia-like syndrome would
      be induced in normal CBA/N mice after intravenous injection of HB-1 cells, and
      the death of mouse happened within about two weeks. In general, leukemic cells
      transplanted into the mice would infiltrate into the hematopoietic organs, lungs,
      kidneys and liver. An interesting observation in our study was that HB-1 cells
      were present not only in the lung, kidney, and liver but also in the cerebrum and
      cerebellum. It was beyond our expectation that the leukemic cells could go
      through the blood-brain barrier in most circumstances. On the basis of the
      observation, we expect that HB-1 cells could be used as a very useful model to
      elucidate the mechanism of infiltrating the blood-brain barrier for certain type
      of cells.

PMID- 16906341
TI  - [Isolation of neural stem cells from the spinal cords of human fetus.].
AB  - Neural stem cells are a potential therapeutic source for cellular transplantation
      therapy in neurological diseases. The present paper was aimed to investigate
      whether neural stem cells could be obtained from the spinal cords of low
      temperature preserved abortuses. Fourteen weeks old abortuses were stored in a
      refrigerator at 4 degrees C without any additional treatments for 2, 6 and 12 h
      before use. The spinal cords were anatomized out and divided into cervical cords,
      thoracic cords and lumbar/sacral cords. Then the spinal cord segments were used
      for cell culture separately. Neural stem cells were isolated from the segments
      and cultured in bFGF, EGF and N2 supplement containing free-serum DMEM/F12 (1:1)
      medium. In order to examine the differentiation potential, the stem cells were
      induced to differentiate with 5% fetal bovine serum on poly-l-lysine substrate.
      Clonal culture was carried out to demonstrate that the isolated cells met the
      standard of stem cells. Indirect fluorescent immunocytochemistry was used to
      examine the expressions of neural stem cell marker (nestin), neuron marker
      (MAP2), astrocyte marker (GFAP) and cholinergic marker (ChAT). The stem cells in
      different cultures were compared. One-way analysis of variance and Kruskal-Wallis
      test were used for the statistical comparison. As a result, neural stem cells
      were obtained from all the spinal cord segments with different postmortem
      intervals. Both the cells on the surface and inside the neurospheres showed
      nestin immunoreactivity. Therefore, nearly all the cells that composed the
      neurospheres were nestin-positive undifferentiated cells. When the spheres were
      induced to differentiate, they could yield GFAP-positive astrocytes and MAP2
      positive neurons including ChAT-positive cholinergic neurons. Primary
      neurospheres could be dissociated mechanically, expand in subcultures and
      maintain the differentiation potential. In clonal cultures, single cells from a
      single primary sphere could give rise to new neurospheres, which had the same
      differentiation potential as the primary spheres. The lumbar/sacral cord cultures
      gave rise to the most abundant primary neurospheres. When the preservation time
      of the fetus was prolonged to 12 h, the number of primary neurospheres decreased
      sharply. The clonal formation and phenotype capacity were similar in all
      cultures. In conclusion, spinal neural stem cells can be isolated from low
      temperature preserved abortuses and represent an alternative source for
      experimental and potential therapeutic purposes.

PMID- 16906342
TI  - [Preparation and identification of monoclonal antibody against human
      thrombomodulin.].
AB  - To produce specific monoclonal antibody (McAb) against human thrombomodulin
      (hTM), the full-length hTM cDNA-expressing plasmid pThr402 was transfected into
      CHO cells by Lipofectamine 2000 reagent. The hTM-expressing CHO cells, which was
      confirmed by flow cytometry and Western blot, were obtained by G418 selection.
      Then the McAb against hTM was prepared with classic hybridoma technique. A cell
      line of CHO-TM5 with high level of hTM was used to immunize female Balb/c mice 3
      times at an interval of 4 weeks. On the third day after the third immunization,
      mice were sacrificed and spleen cells were harvested to prepare hybridoma cells
      with SP2/0 cells at the ratio of 10 to 1. Hybridoma cells were then cultured at
      96-well plates for screening. Cellular enzyme-linked immunoabsorbent assay
      (CELISA) was applied twice. The first CELISA was done with polythene ELISA plate
      with a monolayer of CHO-TM5 cells. The positive clones from the first screen were
      then selected by reacting with similar screening ELISA plate but with CHO cell
      monolayer instead. Only clones that were positive for the first screening and
      negative for the second screening were kept, and called as CHO-TM5(+)CHO(-)
      hybridoma cells. Balb/c mice were intraperitoneally injected with the selected
      hybridoma cells. Ascites were collected and monoclonal antibodies were purified
      using FPLC, and its Ig class, subclass, and titer were then determined
      respectively. The specificity of the yielded McAb was identified with CELISA,
      flow cytometry, ABC immunohistochemistry and immunoblotting. One line of
      hybridoma cells with high expression of specific McAb against hTM, NH-1, was
      obtained. The Ig subclass of the McAb was IgG1 and the titer of ascitic McAb was
      1x10(-6). Flow cytometry, CELISA and Western blot assays demonstrated that McAb
      NH-1 could specifically recognize hTM expressed in CHO-TM5 cells and human
      umbilical vascular endothelial cells. Meanwhile, the tissue specificity of
      antigen recognized by McAb NH-1 was identified by immunohistochemical ABC
      staining. NH-1 can specifically recognize the natural hTM expressed mainly in
      vascular endothelial cells, which will potentially be useful for investigation of
      the functions and clinic values of hTM.

PMID- 16906345
TI  - Short Commentary on "Acute urinary retention due to benign inflammatory nervous
      diseases" by Sakakibara et al. in J Neurol (2006) 253:1103-1110.

PMID- 16906346
TI  - Periventricular heterotopia with complete agenesis of the corpus callosum : a
      case report.

PMID- 16906348
TI  - Ethics and the science of animal minds.
AB  - Ethicists have commonly appealed to science to bolster their arguments for
      elevating the moral status of nonhuman animals. I describe a framework within
      which I take many ethicists to be making such appeals. I focus on an apparent gap
      in this framework between those properties of animals that are part of the
      scientific consensus, and those to which ethicists typically appeal in their
      arguments. I will describe two different ways of diminishing the appearance of
      the gap, and argue that both of them present challenges to ethicists seeking a
      firm scientific basis for their claims about the moral status of animals. I argue
      that more clarity about the role of appeals to science by applied ethicists leads
      to questions about the effectiveness of such appeals, and that these questions
      might best be pursued empirically.

PMID- 16906349
TI  - Moral agency in other animals.
AB  - Some philosophers have argued that moral agency is characteristic of humans alone
      and that its absence from other animals justifies granting higher moral status to
      humans. However, human beings do not have a monopoly on moral agency, which
      admits of varying degrees and does not require mastery of moral principles. The
      view that all and only humans possess moral agency indicates our underestimation
      of the mental lives of other animals. Since many other animals are moral agents
      (to varying degrees), they are also subject to (limited) moral obligations,
      examples of which are provided in this paper. But, while moral agency is
      sufficient for significant moral status, it is by no means necessary.

PMID- 16906350
TI  - Regarding animals: mental life, moral status, and use in biomedical research: an
      introduction to the special issue.

PMID- 16906351
TI  - Water quality during development and apportionment of pollution from rivers in
      Tapeng Lagoon, Taiwan.
AB  - This work investigated water samples collected from Tapeng Lagoon, Taiwan. Factor
      analysis was conducted to explain the characteristics and the variation in the
      quality of water during the disassembly of oyster frames and fishery boxes. The
      result shows that the most important latent factors in Tapeng Lagoon are the
      ocean factor, primary productivity factor, and the fishery pollution factor.
      Canonical discriminant analysis is applied to identify the source of pollution in
      neighboring rivers outside Tapeng Lagoon. The two constructed discriminant
      functions (CDFs) showed markedly contribution to all discriminant variables, and
      that total nitrogen, algae, dissolved oxygen and total phosphate, combined in the
      nutrient effect factor. The recognition capacities in these two CDFs were 95.6%,
      4.4%, respectively. The water quality in the Kaoping river most strongly
      determined that in the Tapeng Lagoon the best is. And disassembling the oyster
      frames and fishery boxes improves the water quality markedly. However,
      environmental topographic conditions indicate that strengthening stream pollution
      prevention and to constructing another entrance to the ocean are the best
      approaches for improving the quality of water in Tapeng Lagoon, especially by
      reducing eutrophication. These approaches and results yield useful information
      concerning habitat recovery and water resource management.

PMID- 16906352
TI  - Toxic metals in the Austrian pine (pinus nigra) bark in the Thrace region,
      Turkey.
AB  - Austrian pine (Pinus nigra) bark was collected in thirty-seven localities in the
      Thrace region, Turkey, for the determination of airborne toxic metal
      distribution. Five toxic metals, As, Cd, Cu, Pb, and Zn, were monitored using
      atomic absorption spectrometry. Distribution maps of toxic elements in the region
      were plotted according to Geographic Information System technology. In general,
      the concentrations of all investigated elements were not high in the region apart
      from the vicinity of big cities, Tekirdag, Istanbul and, close to Bulgarian
      border. However, the highest concentrations were not at pollution level. They
      have a similar distribution pattern throughout the region.

PMID- 16906353
TI  - The brain as a system of nested but partially overlapping networks. Heuristic
      relevance of the model for brain physiology and pathology.
AB  - A new model of the brain organization is proposed. The model is based on the
      assumption that a global molecular network enmeshes the entire central nervous
      system. Thus, brain extra-cellular and intra-cellular molecular networks are
      proposed to communicate at the level of special plasma membrane regions (e.g.,
      the lipid rafts) where horizontal molecular networks can represent input/output
      regions allowing the cell to have informational exchanges with the extracellular
      environment. Furthermore, some "pervasive signals" such as field potentials,
      pressure waves and thermal gradients that affect large parts of the brain
      cellular and molecular networks are discussed. Finally, at least two learning
      paradigms are analyzed taking into account the possible role of Volume
      Transmission: the so-called model of "temporal difference learning" and the
      "Turing B-unorganised machine". The relevance of this new view of brain
      organization for a deeper understanding of some neurophysiological and
      neuropathological aspects of its function is briefly discussed.

PMID- 16906355
TI  - Evaluation of acute antiapoptotic effects of Li+ in neuronal cell cultures.
AB  - Li(+) exerts protective effect against several neurotoxins in neuronal cell
      preparations. Here we examined the antiapoptotic effects of GSK3beta in
      cerebellar granule neurons (CGNs) in the presence of several neurotoxins. Acute
      treatment with Li(+) protected neurons against nocodazole and serum/potassium
      (S/K) deprivation, but were ineffective against kainic acid and MPP(+). Li(+) 5
      mM also decreased caspase-3 activation induced by nocodazole and S/K deprivation
      as measured by Ac-DEVD-p-nitroaniline and the breakdown of alpha-spectrin. All
      the neurotoxins used in the present study activated GSK3beta, evaluated with a
      specific antibody phospho-GSK-3beta (Ser9) by Western-blot and
      immunocytochemistry and were always inhibited by Li(+) 5 mM. Our results
      implicate Li(+) in the regulation of apoptosis mediated by caspase activation
      (Type I). Furthermore inhibition of GSK3beta by acute treatment with Li(+) 5 mM
      is not an indicator of neuroprotection. The acute antiapoptotic function of Li(+)
      is discussed in terms of its inhibition of Type I pathway, the intrinsic
      (mitochondrial) apoptotic pathway in cerebellar granule cells.

PMID- 16906357
TI  - Transport of peptides, amino acids, and derivatives.

PMID- 16906354
TI  - Nicotinic receptor agonists as neuroprotective/neurotrophic drugs. Progress in
      molecular mechanisms.
AB  - In the present work we reviewed recent advances concerning
      neuroprotective/neurotrophic effects of acute or chronic nicotine exposure, and
      the signalling pathways mediating these effects, including mechanisms implicated
      in nicotine addiction and nAChR desensitization. Experimental and clinical data
      largely indicate long-lasting effects of nicotine and nicotinic agonists that
      imply a neuroprotective/neurotrophic role of nAChR activation, involving mainly
      alpha7 and alpha4beta2 nAChR subtypes, as evidenced using selective nAChR
      agonists. Compounds interacting with neuronal nAChRs have the potential to be
      neuroprotective and treatment with nAChR agonists elicits long-lasting
      neurotrophic effects, e.g. improvement of cognitive performance in a variety of
      behavioural tests in rats, monkeys and humans. Nicotine addiction, which is
      mediated by interaction with nACh receptors, is believed to involve the
      modification of signalling cascades that modulate synaptic plasticity and gene
      expression. Desensitization, in addition to protecting cells from uncontrolled
      excitation, is recently considered as a form of signal plasticity. nAChR can
      generate these longe-lasting effects by elaboration of complex intracellular
      signals that mediate medium to long-term events crucial for neuronal maintenance,
      survival and regeneration. Although a comprehensive survey of the gene-based
      molecular mechanisms that underlie nicotine effects has yet not been performed a
      growing amount of data is beginning to improve our understanding of signalling
      mechanisms that lead to neurotrophic/neuroprotective responses. Evidence for an
      involvement of the fibroblast growth factor-2 gene in nAChR mechanisms mediating
      neuronal survival, trophism and plasticity has been obtained. However, more work
      is needed to establish the mechanisms involved in the effects of nicotinic
      receptor subtype activation from cognition-enhancing and neurotrophic effects to
      smoking behaviour and to determine more precisely the therapeutic objectives in
      potential nicotinic drug treatments of neurodegenerative diseases.

PMID- 16906356
TI  - CSF diagnosis of Alzheimer's disease and dementia with Lewy bodies.
AB  - Differential diagnosis of Alzheimer's disease (AD) and dementia with Lewy bodies
      (DLB) is often crucial. CSF Tau protein and Amyloid-beta (A beta) peptides have
      shown diagnostic value for the diagnosis of AD, but discrimination from DLB was
      poor.Herein, we investigate CSF of 18 patients with probable AD, 25 with probable
      DLB and 14 non-demented disease controls (NDC) by A beta-SDS-PAGE/immunoblot and
      commercially available ELISAs for A beta1-42 and tau. CSF A beta peptide patterns
      and tau exhibited disease specific alterations among AD and DLB. The ratio of A
      beta1-42 to A beta1-38 and A beta1-42 to A beta1-37, respectively, in combination
      with absolute tau, yielded a sensitivity and specificity of 100 and 92%,
      respectively. We conclude that CSF A beta peptide patterns and tau levels reflect
      disease-specific pathophysiological pathways of these dementias as distinct
      neurochemical phenotypes. Combined evaluation of these biomarkers provides a
      reasonable accuracy for differential diagnosis of AD and DLB.

PMID- 16906358
TI  - Pseudoaneurysm of the membranous septum, case report and review of the
      literature.
AB  - Pseudoaneurysm (dissecting aneurysm) of the membranous septum is a rare occasion.
      Clinically, aneurysms and pseudoaneurysms not only have the potential to reduce
      ventricular size, but also can be further complicated by rupture of the aneurysm
      and by promoting tricuspid insufficiency, aortic valve prolapse, ventricular
      outflow tract obstruction, and bacterial endocarditis. We describe a case in
      which a pseudoaneurysm of the membranous septum was identified protruding into
      the left outflow tract.

PMID- 16906359
TI  - The development of stomach during the fetal period.
AB  - The objective of this study was to explore the fetal development of the stomach,
      its morphology and relationship with neighboring structures. The study is carried
      out in 2003 using 160 human embryos and fetuses (81 males and 79 females) aged
      between 9 and 40 weeks of gestation. None of the cases had any external pathology
      or anomaly. Its topographical localization and relationship with surrounding
      structures were revealed with anatomical dissections. Width and height of the
      stomach, lengths of the greater and lesser curvatures, the angle between
      horizontal and vertical axes of the stomach and types of stomach were
      established. During the fetal life stomach was most commonly located above the
      transverse axis passing through the umbilicus, in left and right hypochondrium
      (81%). There were significant differences among trimester groups with respect to
      the localization of the stomach in the quadrants (P < 0.001). There were no
      significant sex differences in parameters. After the second trimester, the height
      of the stomach increased more than the width of the stomach and anterior
      abdominal height. The angle of stomach decreased from 100 degrees to 50 degrees
      throughout the fetal period. During the fetal period, wide angles stomach was
      more common in the first(f) and second trimesters while acute-angled stomach was
      more common in the third trimester and term fetuses. Diagnosis and treatment of
      fetal anomalies and pathologies of the stomach requires knowledge of fetal
      anatomy of the stomach. Data acquired in this study are believed to contribute to
      the studies of obstetrics, perinatology, forensic medicine and fetal pathology on
      fetal development of the stomach, and diagnosis and treatment of its anomalies,
      pathologies, and variations.

PMID- 16906360
TI  - Phenol contents, oxidase activities, and the resistance of coffee to the leaf
      miner Leucoptera coffeella.
AB  - We examined the role of phenolic compounds, and the enzymes peroxidase and
      polyphenol oxidase, in the expression of resistance of coffee plants to
      Leucoptera coffeella (Lepidoptera: Lyonetiidae). The concentrations of total
      soluble phenols and chlorogenic acid (5-caffeoylquinic acid), and the activities
      of the oxidative enzymes peroxidase (POD) and polyphenol oxidase (PPO), were
      estimated in leaves of Coffea arabica, C. racemosa, and progenies of crosses
      between these species, which have different levels of resistance, before and
      after attack by this insect. The results indicate that phenols do not play a
      central role in resistance to the coffee leaf miner. Differences were detected
      between the parental species in terms of total soluble phenol concentrations and
      activities of the oxidative enzymes. However, resistant and susceptible hybrid
      plants did not differ in any of these characteristics. Significant induction of
      chlorogenic acid and PPO was only found in C. racemosa, the parental donator of
      the resistance genes against L. coffeella. High-performance liquid chromatography
      (HPLC) analysis also showed qualitative similarity between hybrids and the
      susceptible C. arabica. These results suggest that the phenolic content and
      activities of POD and PPO in response to the attack by the leaf miner may not be
      a strong evidence of their participation in direct defensive mechanisms.

PMID- 16906361
TI  - Phloem alkaloid tolerance allows feeding on resistant Lupinus angustifolius by
      the aphid Myzus persicae.
AB  - We examined the hypothesis that the polyphagous green peach aphid (Myzus
      persicae) shows clone-specific adaptation to the narrow-leafed lupin (Lupinus
      angustifolius) containing toxic quinolizidine alkaloids. We compared the
      performance of a lupin-feeding clone of M. persicae from Western Australia to
      that of nine clones of the same species collected from eastern Australian
      locations, where narrow-leafed lupins rarely occur. Mean relative growth rate
      (MRGR) and colonization ability varied among the M. persicae clones on one aphid
      susceptible and two aphid-resistant lupin varieties. The performance of the lupin
      feeding clone was better than that of all other clones on the resistant narrow
      leafed lupin varieties "Tanjil" and "Kalya", indicating that successful lupin
      feeding is not a characteristic of the species. Gas chromatography-mass
      spectrometry analyses (GC-MS) of phloem from the different lupin varieties
      detected differences in the quantities of two alkaloid compounds identified as 13
      OH-lupanine and lupanine. The lupin-feeding M. persicae clone also showed better
      performance on artificial diet amended with lupanine. The results suggest that
      the M. persicae clone collected from Western Australia is adapted to feed
      successfully on narrow-leafed lupin, and that this adaptation may involve
      improved tolerance of lupanine in its diet.

PMID- 16906362
TI  - Palatability of macroalgae that use different types of chemical defenses.
AB  - This study compared algal palatability and chemical defenses from subtropical
      green algae that may use different types of defense systems that deter feeding by
      the rock-boring sea urchin Echinometra lucunter. The potential defense systems
      present include (1) the terpenoid caulerpenyne and its activated products from
      Caulerpa spp., and (2) dimethylsulfoniopropionate (DMSP)-related defenses in Ulva
      spp. Secondary metabolites from these chemical groups have been shown to deter
      feeding by various marine herbivores, including tropical and temperate sea
      urchins. Live algal multiple-choice feeding assays and assays incorporating algal
      extracts or isolated metabolites into an artificial diet were conducted. Several
      green algae, including Ulva lactuca, Caulerpa prolifera, and Cladophora sp., were
      unpalatable. Nonpolar extracts from U. lactuca deterred feeding, whereas nonpolar
      extracts from C. prolifera had no effect on feeding. Polar extracts from both
      species stimulated feeding. Caulerpenyne deterred feeding at approximately 4% dry
      mass; however, dimethyl sulfide and acrylic acid had no effect at natural and
      elevated concentrations. E. lucunter is more tolerant than other sea urchins to
      DMSP-related defenses and less tolerant to caulerpenyne than many reef fish.
      Understanding the chemical defenses of the algae tested in this study is
      important because they, and related species, frequently are invasive or form
      blooms, and can significantly modify marine ecosystems.

PMID- 16906363
TI  - On the subject of vascular surgery training: the educational rubric.

PMID- 16906364
TI  - 31st Annual IUGA Meeting, Athens, Greece, 6-9 September 2006. Abstracts.

PMID- 16906369
TI  - The clinical application of etanercept in Chinese patients with rheumatic
      diseases.
AB  - Over a 2-year period, to evaluate the efficacy and safety of biologic agents,
      etanercept (25 mg twice per week, s.c.) was used to treat 57 rheumatoid arthritis
      (RA) patients, 9 ankylosing spondylitis (AS) patients, 6 psoriatic arthritis
      (PSA) patients, and 4 juvenile rheumatoid arthritis (JRA) patients. In addition
      to inflammatory arthritis, I have used this tumor necrosis factor (TNF) blocker
      in other rheumatic diseases including idiopathic thrombocytopenic purpura (ITP),
      Behcet's disease with intractable oral ulcer, fibromyalgia syndrome, and systemic
      lupus erythematosis with intractable pleural effusion and acute lumbar disc
      herniation. For RA, after 6 months of etanercept treatment, all the parameters
      including number of swollen joints, number of tender joints, disease activity
      score, erythrocyte sedimentation rate, C-reactive protein, and global health
      status were rapidly improved (P < 0.001 or P < 0.0001). The anticyclic
      citrullinated peptide (anti-CCP) antibody and rheumatoid factor also
      significantly declined. For spondyloarthropathy, it also gave a similar effect as
      to RA. Both Bath Ankylosing Spondylitis Disease Activity Index and Bath
      Ankylosing Spondylitis Functional Index also improved. One of the two cases with
      Behcet's disease with intractable oral ulcer had a long-term remission after
      etanercept. The other Behcet's disease patient with oral ulcer and another with
      ITP obtained a good response temporarily. The short-term use of etanercept (<3
      months) did not bring a significant effect for cases of fibromyalgia syndrome,
      pleural effusion, and lumbar disc herniation. In conclusion, a dramatic and rapid
      clinical response in different kinds of arthritis patients can be achieved by
      etanercept. Moreover, the TNF-alpha inhibitor also can treat other severe
      rheumatic-related symptoms. In general, except for a few cases with infection and
      two cases with malignancy, etanercept was safe in our arthritis patients. We need
      to study a larger number of patients in order to better understand the efficacy
      and safety of etanercept.

PMID- 16906368
TI  - Cartilage destruction by matrix degradation products.
AB  - The progressive destruction of articular cartilage is one of the hallmarks of
      osteoarthritis and rheumatoid arthritis. Cartilage degradation is attributed to
      different classes of catabolic factors, including proinflammatory cytokines,
      aggrecanases, matrix metalloproteinases, and nitric oxide. Recently, matrix
      degradation products generated by excessive proteolysis in arthritis have been
      found to mediate cartilage destruction. These proteolytic fragments activate
      chondrocytes and synovial fibroblasts via specific cell surface receptors that
      can stimulate catabolic intracellular signaling pathways, leading to the
      induction of such catalysts. This review describes the catabolic activities of
      matrix degradation products, especially fibronectin fragments, and discusses the
      pathologic implication in cartilage destruction in osteoarthritis and rheumatoid
      arthritis. Increased levels of these degradation products, found in diseased
      joints, may stimulate cartilage breakdown by mechanisms of the kind demonstrated
      in the review.

PMID- 16906370
TI  - Acceptability and usefulness of mizoribine in the management of rheumatoid
      arthritis in methotrexate-refractory patients and elderly patients, based on
      analysis of data from a large-scale observational cohort study.
AB  - This report documents the results of a study performed to examine clinical use of
      mizoribine (MZR), using data from a large-scale prospective cohort study, IORRA
      (Institute of Rheumatology Rheumatoid Arthritis). The number of patients with RA
      entered in this study from October 2000 through October 2003 was 6238. Three
      hundred and six patients (4.9%) received MZR therapy. Mizoribine users who were
      taking methotrexate (MTX) (MTX-MZR group, n = 94) and over 70 years of age
      (elderly group, n = 45) were collected. Cumulative retention rates of MZR were
      calculated by Kaplan-Meier analysis. Median drug survival of MZR was 28 months
      for the poor responders to MTX and 43 months for the poor responders to MZR, with
      no significant difference between these groups. Cumulative retention rate of MZR
      in the elderly group did not show a significant difference compared to that in
      patients aged under 70 years. Ten patients (10.6%) in the MTX-MZR group and 10
      patients (22.2%) in the elderly group experienced adverse effects of MZR. None of
      these adverse effects was serious. This study indicated that, although MZR has
      not been frequently prescribed for RA patients, it may be useful and relatively
      safe for patients who are poor responders to MTX as an additional regimen to MTX
      therapy as well as for elderly patients.

PMID- 16906371
TI  - Doppler sonographic comparative study on usefulness of synovial vascularity
      between knee and metacarpophalangeal joints for evaluation of articular
      inflammation in patients with rheumatoid arthritis treated by infliximab.
AB  - We used Doppler sonography to evaluate the therapeutic effects of infliximab on
      the knee and metacarpophalangeal (MCP) joints of 10 patients with rheumatoid
      arthritis (RA), based on the color flow signals (CFS) and resistance index (RI)
      of synovial vascularity. After three injections of infliximab, we observed
      significant improvement in numbers of tender joints (P < 0.01), values of C
      reactive protein (CRP) (P < 0.01), erythrocyte sedimentation rate (ESR) (P <
      0.001), disease activity scores including tender joints, swollen joints, and ESR
      (DAS28-E3) (P < 0.0001), and CFS of knee (P < 0.001) and MCP (P < 0.05) joints.
      There was no significant improvement in RI values of knee or MCP joints after the
      therapy. We observed significant correlation between CFS of knee joints (knee
      CFS) and values of CRP (P < 0.01), ESR (P < 0.01), and DAS28-E3 (P < 0.05), but
      not between CFS of MCP joints (MCP-CFS) and values of CRP, ESR, and DAS28-E3.
      However, no significant correlation was observed between 10 difference values
      (before values-after values) of CFS grades of knee or MCP joints and 10
      difference values each of CRP, ESR, or DAS28-E3. The knee joints are more
      suitable than MCP joints for obtaining CFS in Doppler sonography, and are more
      useful than MCP joints for evaluation.

PMID- 16906372
TI  - Altered peptide ligands control type II collagen-reactive T cells from rheumatoid
      arthritis patients.
AB  - We previously reported that peripheral blood mononuclear cells from HLA-DRB1*0101
      Japanese patients with rheumatoid arthritis (RA) were highly reactive to 256-271
      peptide of type II collagen (CII). In this report, we tried to regulate the CII
      reactivity of T cells from RA patients with HLA-DRB1*0101 by altered peptide
      ligand (APL), which is a single amino acid substitution of the T-cell epitope on
      CII 256-271 peptide. Antagonistic activity of 21 APLs was assessed using three
      different T-cell lines. Results showed that 262 (G-->A) APL of CII 256-271
      exhibited antagonistic activity in all T-cell lines and it was suggested that the
      application of CII APL might be a new therapeutic strategy in the regulation of
      RA.

PMID- 16906373
TI  - Significant elevation of IgG anti-WRN (RecQ3 RNA/DNA helicase) antibody in
      systemic sclerosis.
AB  - Werner syndrome, caused by the homologous mutation of RecQ3 RNA/DNA helicase
      (WRN), is often misdiagnosed as systemic sclerosis (SSc) because of apparent
      similar skin changes and its relatively high frequency in Japan. The present
      study was undertaken to determine whether anti-WRN antibodies assayed by specific
      enzyme-linked immunosorbent assay occur in 41 SSc patients (30 diffuse and 11
      limited types) and, if so, to determine any clinical association, such as skin
      sclerosis. Serum level of IgG anti-WRN antibody in SSc was significantly higher
      than that from 30 age- and sex-matched normal volunteers (P < 0.001). The serum
      level of IgG anti-WRN antibody in diffuse type SSc was significantly higher than
      the limited type (P < 0.05). A significant correlation was observed between serum
      levels of IgG anti-topoisomerase I antibody and IgG anti-WRN antibody in the same
      samples from SSc (P < 0.05). Moreover, in 119 normal healthy individuals aged
      from 0 to 99 years, a statistically significant correlation (P < 0.001) existed
      between serum level of IgG anti-WRN antibody and advancing age. A significantly
      higher level of IgG autoantibody specific for WRN detected in diffuse than in
      limited type SSc and normal may contribute to the pathogenesis of skin sclerosis
      in SSc.

PMID- 16906374
TI  - CD19/22 balance relates to improvement of disease activity in systemic lupus
      erythematosus.
AB  - B cells in patients with systemic lupus erythematosus (SLE) are hyperactivated
      and B-cell receptor signal transduction may be affected by various response
      regulators. CD19 and CD22 play a major role as regulators of B-cell response.
      Therefore, we examined CD19 and CD22 expressions on B cells of patients with SLE,
      and how they were related to disease activity. Thirty-one patients with active
      SLE were selected and enrolled in this study. Evaluation of CD19 and CD22
      expressions on B cells was performed prior to and after treatments with flow
      cytometry analysis. Disease activity was determined according to the SLE disease
      activity index score. CD19 and CD22 expressions on B cells in SLE patients
      revealed no significant differences when compared with the controls. However,
      improvement of SLE was recognized among patients with an increased ratio of CD22
      positive cells. Our results suggest that this balance is a useful marker for
      determining improvement of SLE disease activity, although the CD19/22 balance
      does not contribute to the pathogenesis of SLE.

PMID- 16906375
TI  - A case of systemic lupus erythematosus expressing intractable thrombocytopenia
      remedied effectively by intermittent and continuous administrations of a small
      amount of immune globulin.
AB  - We describe a case where intermittent and continuous administrations of a small
      amount of immune globulin were effective in the treatment of refractory chronic
      immune thrombocytopenic purpura by systemic lupus erythematosus (SLE). Steroid
      pulse therapy and cyclophosphamide pulse therapy were considered for
      thrombopenia. However, the patient had compressed fracture of the lumbar
      vertebrae due to osteoporosis and right external malleolus ulcer with
      complications of infection. Therefore, high-dose intravenous immune globulin
      (IVIG) therapy (400 mg/kg daily for 5 consecutive days) was administered. Then,
      as a maintenance therapy, a small amount of 400 mg/kg for 1 day (400 mg/kg
      monthly) was given in an intermittent and continuous manner, which resulted in
      improvement of thrombocytopenia and reduction of the amount of steroid
      administered.

PMID- 16906376
TI  - [18F]fluorodeoxyglucose positron emission tomography is a useful tool to diagnose
      the early stage of Takayasu's arteritis and to evaluate the activity of the
      disease.
AB  - Takayasu's arteritis (TA) is a rare disease that can be difficult to diagnose in
      its early stage. A young woman with a fever and neck pain was thought to have TA,
      although computed tomographic angiography did not show any specific changes of
      the arteries. [(18)F]fluorodeoxyglucose positron emission tomography ([(18)F]FDG
      PET) was performed to detect the source of the inflammation. Specific
      accumulation of [(18)F]FDG-6-phosphate in the thoracic aorta and its direct
      branches was observed, leading to a diagnosis of TA. [(18)F]FDG-PET is therefore
      considered to be useful for the diagnosis of early-stage TA.

PMID- 16906377
TI  - A case of spontaneous hemoarthrosis after a total knee arthroplasty.
AB  - A 63-year-old woman with osteoarthritis had undergone right total knee
      arthroplasty. Nineteen months later, the patient presented with a recurrent
      hemoarthrosis. Open arthrotomy revealed hypertrophic synovium with small clots in
      the suprapatellar pouch, but entrapment of synovial tissues could not be
      observed. Histological examination of the extirpated specimen showed fibrous
      hypertrophy of synovium. The patient has no symptoms 51 months after surgery.

PMID- 16906378
TI  - Development of interstitial pneumonia in a rheumatoid arthritis patient treated
      with infliximab, an anti-tumor necrosis factor alpha-neutralizing antibody.
AB  - Infliximab, an anti-tumor necrosis factor (TNF)-alpha antibody, was introduced to
      a 66-year-old woman with methotrexate (MTX)-resistant rheumatoid arthritis (RA).
      Although the TNF-blocking therapy was successful, she developed noninfectious
      interstitial pneumonia (IP) after a second infusion of infliximab. In most cases
      reported previously, infliximab-associated noninfectious IP occurred after a
      second or third infusion of infliximab, and this type of IP was more fatal in
      comparison with cases associated with MTX treatment alone. Keeping a sharp
      lookout on IP development during this period is crucial to the success of
      infliximab treatment. After MTX discontinuation and steroid pulse therapy, our
      patient made a dramatic recovery from IP.

PMID- 16906379
TI  - Minocycline-induced vasculitis fulfilling the criteria of polyarteritis nodosa.
AB  - A 47-year-old man who had been taking minocycline for palmoplantar pustulosis
      developed fever, myalgias, polyneuropathy, and testicular pain, with elevated C
      reactive protein (CRP). Neither myeloperoxidase- nor proteinase-3-antineutrophil
      cytoplasmic antibody was positive. These manifestations met the American College
      of Rheumatology 1990 criteria for the classification of polyarteritis nodosa.
      Stopping minocycline led to amelioration of symptoms and normalization of CRP
      level. To our knowledge, this is the second case of minocycline-induced
      vasculitis satisfying the criteria. Differential diagnosis for drug-induced
      disease is invaluable even for patients with classical polyarteritis nodosa.

PMID- 16906380
TI  - Infectious myositis involving the piriformis in a patient with rheumatoid
      arthritis.
AB  - A 49-year-old Japanese woman treated with oral corticosteroids, methotrexate, and
      infliximab for malignant rheumatoid arthritis was admitted because of fever and
      low back pain. The white blood cell count and C-reactive protein concentration
      were elevated. Lumbar and pelvic computed tomography showed enlargement of the
      piriformis muscle including a hypodense area consistent with gas formation. The
      patient was treated successfully for infectious myositis with intravenous
      antibiotics.

PMID- 16906382
TI  - Early morning neutropenia in a patient with systemic lupus erythematosus.

PMID- 16906381
TI  - Tacrolimus treatment for refractory lupus cystitis.
AB  - A 23-year-old woman presented with recurrence of lupus cystitis, which had been
      in remission under daily administration of a single corticosteroid over a period
      of 8 years. She was treated with increased doses of corticosteroid and
      immunosuppressants, i.e., cyclosporin, cyclophosphamide, azathioprine, and
      salazosulfapyridine, but the cystitis remained active. Since her condition became
      critical by the complication of intestinal pseudo-obstruction, tacrolimus was
      administered. This agent induced a remission promptly without significant adverse
      events in this patient, suggesting an efficacy to lupus cystitis refractory to
      corticosteroid and other immunosuppressants.

PMID- 16906383
TI  - The quorum-sensing molecule N-3-oxododecanoyl homoserine lactone (3OC12-HSL)
      enhances the host defence by activating human polymorphonuclear neutrophils
      (PMN).
AB  - The P. aeruginosa quorum-sensing molecule N-3-oxododecanoyl homoserine lactone
      (3OC12-HSL) interacts not only with bacteria, but also with mammalian cells,
      among others with those of the immune defence system. We focussed on the possible
      interaction of 3OC12-HSL with human polymorphonuclear neutrophils (PMN), because
      these cells are the first to enter an infected site. We found that 3OC12-HSL
      attracts PMN, and up-regulates expression of receptors known to be involved in
      host defence, including the adhesion proteins CD11b/CD18 and the immunoglobulin
      receptors CD16 and CD64. Furthermore, the uptake of bacteria (phagocytosis),
      which is crucial for an efficient defence against infection, was enhanced. Thus,
      recognising and responding to 3OC12-HSL not only attracts the PMN to the site of
      a developing biofilm, but also reinforces their defence mechanisms, and hence
      could be a means to control the infection in an early stage and to prevent
      biofilm formation.

PMID- 16906384
TI  - Analysis of hormonal steroids in fish plasma and bile by coupling solid-phase
      extraction to GC/MS.
AB  - An analytical procedure for the simultaneous determination of twelve endogenous
      steroids (testosterone, androstenedione, 17beta-estradiol, estrone, pregnenolone,
      progesterone, dihydroandrostenedione, dihydrotestosterone, 11alpha
      ketotestosterone, 17alpha-hydroxyprogesterone, 17alpha-hydroxypregnenolone,
      17alpha,20beta-dihydroxy-4-pregnen-3-one) in plasma and bile samples by solid
      phase extraction (SPE) and gas chromatography/mass spectrometry (GC-MS) has been
      developed. After enzymatic hydrolysis for bile samples only, samples were
      concentrated and purified using two successive SPE (C(18) and NH(2)) cartridges.
      Analytes were derivatized with a mixture of N-methyl-N
      (trimethylsilyl)trifluoroacetamide (MSTFA) / mercaptoethanol / ammonium iodide
      (NH(4)I) and determined by GC-MS in selective ion monitoring mode. For most of
      the steroids monitored, recoveries were in the range 90-120% in plasma and in the
      range 60-70% in bile, and the reproducibility was below 10% for the complete
      procedure. Limits of detection obtained ranged from 0.1 to 0.4 ng/g in fish
      plasma and from 1.6 to 14 ng/g in fish bile. The developed method was
      successfully applied to the determination of plasma steroids in flounders
      (Platichthys flesus) collected from two French estuaries.

PMID- 16906385
TI  - Non-metal element detection by radio-frequency glow-discharge optical-emission
      spectrometry (rf-GD-OES) for determination of sol-gel-immobilized nucleotides.
AB  - A new method is presented for qualitative and quantitative determination of non
      metal elements present in organic analyte species immobilized in a sol-gel
      matrix. Nucleic acids were chosen as well-defined relevant biomolecules for which
      element ratios could be used for detection and identification. Solid, lyophilized
      powders of ribose-form nucleotides (AMP, ADP, and ATP) were immobilized/entrapped
      in a methlytrimethoxysilane (mTMOS) sol-gel matrix and monitored for P (I) 214.9
      nm, C (I) 193.0 nm, O (I) 130.2, and N (I) 149.3 nm emission by radio-frequency
      glow-discharge optical-emission spectroscopy (rf-GD-OES). Using the sol-gel
      method, analytical blanks were obtained by use of un-doped sol-gels. Empirical
      formula calculations by use of P (I) and C (I), P (I) and N (I), and P (I) and O
      (I) emission response ratios demonstrate the versatility of the technique as an
      element and species-specific detector. Results show there is high correlation
      between phosphorus and oxygen emission responses and the extent of
      phosphorylation, demonstrating the capacity of the method to produce vital
      qualitative and quantitative information for the specific nucleotide. Absolute
      sub-nanogram detection limits were achieved for all the elements studied.

PMID- 16906386
TI  - Synthetic musk fragrances in environmental Standard Reference Materials.
AB  - Synthetic musk fragrances have been measured in water, air, sediments, sewage
      sludge, and biota worldwide. As the study of the environmental fate and impacts
      of these compounds progresses, the need for Standard Reference Materials (SRMs)
      for these compounds to facilitate analytical method improvement and
      interlaboratory comparisons becomes increasingly important. The National
      Institute of Standards and Technology (NIST) issues environmental matrix SRMs
      with certified concentrations for a variety of persistent organic pollutants
      including polycyclic aromatic hydrocarbons (PAHs), chlorinated pesticides, and
      polychlorinated biphenyl congeners (PCBs). Until now synthetic musk fragrance
      concentrations have not been reported in NIST SRMs. The objective of this study
      was to provide reference values for several commonly detected synthetic musk
      fragrances in several NIST natural matrix SRMs. In this study five polycyclic
      musk fragrances [HHCB (1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta
      gamma-2-benzopyran), AHTN (7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4
      tetrahydronaphthalene), ADBI (4-acetyl-1,1-dimethyl-6-tert-butylindane), AHMI (6
      acetyl-1,1,2,3,3,5-hexamethylindane), and ATII (5-acetyl-1,1,2,6-tetramethyl-3
      isopropylindane] and two nitro musk fragrances [musk xylene (1-tert-butyl-3,5
      dimethyl-2,4,6-trinitrobenzene) and musk ketone (4-tert-butyl-3,5-dinitro-2,6
      dimethylacetophenone)] were measured in selected environmental SRMs. Gas
      chromatography-electron impact mass spectrometry (GC/EI-MS) was used for all
      analyses. HHCB was the most frequently detected synthetic musk fragrance and was
      detected in SRM 2585 Organic Contaminants in House Dust, SRM 2781 Domestic
      Sludge, SRM 1974b Organics in Mussel Tissue (Mytilus edulis), and SRM 1947 Lake
      Michigan Fish Tissue. It was not detected in SRM 1946 Lake Superior Fish Tissue
      or SRM 1945 Organics in Whale Blubber. Concentrations of HHCB in these SRMs
      ranged from 1.12 ng/g in SRM 1947 to 92,901 ng/g in SRM 2781. All of the
      polycyclic musk fragrances were detected in SRM 2781 and all of the target
      compounds were detected in SRM 2585.

PMID- 16906387
TI  - Laser ablation inductively coupled plasma mass spectrometry for direct analysis
      of the spatial distribution of trace elements in metallurgical-grade silicon.
AB  - The spatial distribution and concentration of impurities in metallurgical-grade
      silicon (MG-Si) samples (97-99% w/w Si) were investigated by use of laser
      ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). The spatial
      resolution (120 mum) and low limits of detection (mg kg(-1)) for quality
      assurance of such materials were studied in detail. The volume-dependent
      precision and accuracy of non-matrix-matched calibration for quantification of
      minor elements, using NIST SRM 610 (silicate standard), indicates that LA-ICP-MS
      is well suited to rapid process control of such materials. Quantitative results
      from LA-ICP-MS were compared with previously reported literature data obtained by
      use of ICP-OES and rf-GD-OES. In particular, the distribution of element
      impurities and their relationship to their different segregation coefficients in
      silicon is demonstrated.

PMID- 16906388
TI  - Optimization of the xylan degradation activity of monolithic enzymatic membranes
      as a function of their composition using design of experiments.
AB  - The aim of this work was the development and optimization of enzymatic monolithic
      membranes with high catalytic activity for the degradation of xylan into
      xylooligosaccharides. The chemometric tool design of experiments has been
      utilized here for the first time for the optimization of the enzymatic activity
      of the monolithic membranes based on their constituents. The effect of three
      process variables, including the amount of various monomer contents and the
      porogenic solvents ratio, has been studied on the enzymatic activity of the
      resulted membranes. The experimental design chosen was a central face centred
      with six central points in order to obtain an orthogonal model, with the
      precision of the results being independent of the range of values considered for
      each parameter. The software Modde(c) 6.0 from Umetrics(c) was used to build and
      analyze the results of the experimental design using partial least squares
      regression. The optimization of the suggested model provided the best membrane
      composition to achieve maximum enzymatic activity, which can be related to the
      amount of enzyme immobilized on the monolithic membrane. The predictive capacity
      of the model was evaluated performing additional experiments.

PMID- 16906389
TI  - COX-2 expression of ampullary carcinoma: correlation with different histotypes
      and clinicopathological parameters.
AB  - Epidemiological studies suggest that regular intake of nonsteroidal anti
      inflammatory drugs (NSAIDs) are associated with reduced incidence of
      gastrointestinal cancer. Several lines of evidence indicate that the
      antineoplastic effect of NSAIDs is attributable to COX-2 inhibition. The aim of
      our study was to assess COX-2 expression in a series of primary untreated
      ampullary carcinomas and its possible correlation with clinicopathological
      parameters. In the present study, 45 surgical specimens of invasive ampullary
      carcinomas were histologically classified into pancreaticobiliary, intestinal,
      and unusual types. COX-2 expression by immunohistochemical method was analyzed.
      High COX-2 expression was detected in 35 (77.8%) ampullary carcinomas. Among
      these, 20/21 (95.2%) were classified as intestinal, 9/18 (50%)
      pancreaticobiliary, and 6/6 (100%) unusual type. A significant statistical
      difference in terms of COX-2 expression was found between pancreaticobiliary vs
      intestinal type (P=0.002). Furthermore, a negative significant statistical
      correlation was found between T factor and COX-2 expression (P=0.047). The
      different COX-2 expression among histopathological types supports the concept of
      histogenetical difference of ampullary carcinomas. Furthermore, the high rate of
      COX-2 expression in the intestinal subtype of ampullary carcinoma may represent
      the rational for a histotype-tailored therapy targeting COX-2.

PMID- 16906390
TI  - Pilomatricoma in a pediatric patient.

PMID- 16906391
TI  - Meningoencephalitis due to anthrax: CT and MR findings.
AB  - Anthrax is primarily a disease of herbivores, but it also causes cutaneous,
      respiratory and gastrointestinal infections in humans. Bacillus anthracis is an
      uncommon cause of meningitis and generally produces a haemorrhagic
      meningoencephalitis. We present the CT and MR findings of anthrax
      meningoencephalitis due to the cutaneous form of anthrax in a 12-year-old boy.
      They showed focal intracerebral haemorrhage with leptomeningeal enhancement.

PMID- 16906392
TI  - Adamantinoma in childhood: report of six cases and review of the literature.
AB  - BACKGROUND: Adamantinoma is a rare slow-growing malignant bone tumour. OBJECTIVE:
      To describe the imaging appearances of six childhood cases and review the
      published literature. MATERIALS AND METHODS: The database of the Working Group on
      Paediatric Oncology, Academic Medical Centre/Emma Children's Hospital Amsterdam,
      was searched for cases of adamantinoma. Additionally a literature study was
      performed to identify cases of adamantinoma in childhood. RESULTS: We identified
      six local cases of adamantinoma of the long bones, two boys (age 3 and 8 years)
      and four girls (mean age 8.8 years, range 3.0-14.0 years). The location of the
      tumour was the tibia in five and the tibia and fibula in one patient. In two
      patients initially a different diagnosis was made, which led to a delay in
      appropriate treatment. None of the children showed pulmonary metastases and all
      underwent total gross resection. On follow-up (mean 6.1 years, range 1.6-12.0
      years) all children remained disease-free. Besides a discussion of our six
      patients, imaging features, histopathology, surgical approach and a literature
      review of childhood adamantinomas is presented. CONCLUSION: Although the
      incidence of adamantinoma is low, it is important to recognize this rare bone
      tumour, since in the early stages of the disease adequate treatment will result
      in an excellent prognosis.

PMID- 16906393
TI  - The sonographic characteristics of nontuberculous mycobacterial cervicofacial
      lymphadenitis in children.
AB  - BACKGROUND: Nontuberculous mycobacteria (NTM) are a common cause of chronic
      cervicofacial lymphadenitis in young children. The differential diagnosis
      includes other infections, lymphoepithelial cysts and malignancies. OBJECTIVE: To
      assess the sonographic findings of NTM cervicofacial lymphadenitis in children.
      MATERIALS AND METHODS: We analysed the sonograms of cervicofacial lymph nodes of
      145 children with microbiologically proven NTM lymphadenitis. RESULTS: The size
      of the involved lymph nodes ranged from 1.9 cm to 4.4 cm. Most of the NTM
      patients (85%) presented in a stage of lymph node fluctuation with violaceous
      skin discoloration. On sonography, marked decreased echogenicity was seen in all
      cases. In 133 of the patients (92%) liquefaction with intranodal cystic necrosis,
      nodal matting and adjacent soft-tissue oedema were present. 66 children received
      antibiotic treatment, and the other children underwent surgical excision of the
      involved lymph nodes. In 69% of the patients successfully treated with
      antibiotics, multiple intranodal calcifications were present on sonography after
      1 year. CONCLUSIONS: Sonographic findings can provide additional diagnostic clues
      for NTM lymphadenitis in childhood. A marked decrease of echogenicity in the
      early stages, with intranodal liquefaction in the advanced stages, are universal
      features, albeit not entirely specific. Multiple intranodal calcifications are
      rather characteristic of end-stage mycobacterial infection.

PMID- 16906394
TI  - An altered peptide ligand for naive cytotoxic T lymphocyte epitope of TRP-2(180
      188) enhanced immunogenicity.
AB  - Tyrosinase-related protein-2 (TRP-2) is a non-mutated melanocyte differentiation
      antigen. The TRP-2-recognizing CD8(+) T cells can evoke immune responses to
      melanoma in both humans and mice. Developing epitopes with amino acid
      replacements in their sequences might improve the low immunogenicity against this
      'self' tumor antigen. We designed altered peptide ligands (APLs) of TRP-2((180
      188)) (SVYDFFVWL) with preferred primary and auxiliary HLA-A*0201 molecule anchor
      residue replacement. These APLs were screened for MHC-affinity by affinity
      prediction plots and molecular dynamics simulation, and analyzed in vitro for
      stability and binding-affinity to molecular HLA-A*0201. We also investigated the
      CTLs activities induced by TRP-2 wild-type epitope and the APLs both in vitro in
      human PBMCs and HLA-A2.1/K(b) transgenic mice. The results indicate that TRP-2 2M
      analog simultaneously had stronger binding-affinity and a lower dissociation rate
      to HLA-A*0201, than wild-type peptide. In addition, the analog 2M was superior to
      other APLs and wild-type epitope in terms of immunological efficacy ex vivo as
      measured by the ELISPOT assays of IFN-gamma and granzyme B. These results
      demonstrate that TRP-2 2M is an agonist epitope that can induce anti-tumor
      immunity superior to its wild-type epitope, and has potential application in
      peptide-mediated immunotherapy.

PMID- 16906395
TI  - The effects of Ginkgo biloba extract added to haloperidol on peripheral T cell
      subsets in drug-free schizophrenia: a double-blind, placebo-controlled trial.
AB  - OBJECTIVE: To investigate the effects of Ginkgo biloba extract (EGb)
      administration on T lymphocyte subsets and superoxide dismutase (SOD) levels in
      schizophrenia. METHODS: One hundred and nine schizophrenic inpatients were
      randomly assigned to 12 weeks of treatment with 360 mg/day of EGb plus a stable
      dose of 0.25 mg kg(-1) day(-1) of haloperidol and placebo plus the same dose of
      haloperidol using a double-blind design. Clinical efficacy was determined using
      the Brief Psychiatric Rating Scale (BPRS), Scale for Assessment of Positive
      Symptoms, and Scale for Assessment of Negative Symptoms. T lymphocytes (CD3+), T
      helper cells (CD4+), T suppressor cells (CD8+), and IL-2-secreting cells were
      measured using the alkaline phosphatase/antialkaline phosphatase technique; and
      SOD levels were measured by radioimmunometric assay at baseline and at
      posttreatment, as compared to 30 sex- and age-matched normal subjects. RESULTS:
      Patients demonstrated significantly lower CD3+, CD4+, and IL-2-secreting cells,
      together with CD4/CD8 ratio, and significantly higher blood SOD levels than did
      healthy controls at baseline. There was a significantly negative relationship
      between SOD and CD4+ cells in the schizophrenic group at baseline. After a 12
      week treatment, CD3+, CD4+, and IL-2-secreting cells, together with CD4/CD8
      ratio, showed a significant increase, but a significant decrease in SOD levels in
      the EGb group. There was only a significant increase in CD4+ cells but no change
      in SOD levels in the placebo group. There was a significant correlation between
      the change in CD4+ cells at posttreatment vs pretreatment and a reduction of BPRS
      total score in the whole patient group. CONCLUSIONS: EGb may improve the
      decreased peripheral immune functions in schizophrenia. The beneficial effects of
      EGb on the immune systems and the improvement of schizophrenic symptoms may be
      medicated through its antioxidant activity.

PMID- 16906396
TI  - Localisation of bullous pemphigoid antigen 180 (BP180) in cultured human
      keratinocytes: functionally relevant modification by calcium.
AB  - The expression of BP180 has previously been demonstrated to be influenced by both
      calcium (Ca(2+)) concentration and binding of anti-BP180-antibodies in cultured
      keratinocytes of the skin squamous cell carcinoma line DJM-1. Here, BP180
      expression was studied in cultured normal human epidermal keratinocytes by
      confocal laser scanning microscopy. We exploited an experimental system, in which
      BP180 was previously shown to mediate, upon incubation with anti-BP180
      antibodies, a specific signal-transducing event that leads to the release of
      inflammatory mediators, such as IL-8 from cultured normal human epidermal
      keratinocytes (NHEK). We found that without addition of BP180-specific IgG, BP180
      is predominantly expressed on the cell surface irrespective of the Ca(2+)
      concentration. In contrast, cell surface BP180 was greatly reduced in NHEK kept
      in high Ca(2+) medium after incubation with BP180-specific IgG for 12 h compared
      to low Ca(2+) medium. This effect was seen with antibodies to both N- and C
      terminal fragments of the BP180 ectodomain, respectively. In addition, a slightly
      higher BP180 expression was found in NHEK cultured in low compared to high Ca(2+)
      medium by Western blotting. Interestingly, in contrast to NHEK kept under low
      Ca(2+ )conditions, in NHEK grown in high Ca(2+) medium, no elevated levels of IL
      8 were released after treatment of cells with anti-BP180 IgG compared to normal
      IgG. Our data indicate that the Ca(2+)-modulated expression of BP180 is
      functionally relevant. This finding sheds further light on the complex
      pathomechanism in blister formation of BP180-related autoimmune blistering skin
      diseases.

PMID- 16906397
TI  - Pyomyositis: a limping diagnosis.

PMID- 16906398
TI  - Duration of isolation of children with influenza A treated with oseltamivir.
AB  - The duration of fervescence (24 hours in children or 30 hours in adults) was
      shorter in the oseltamivir group than in the placebo group. According to a
      Japanese law enacted before oseltamivir therapy became available, schoolchildren
      with influenza must be isolated 48 hours after defervescence. Our data suggest
      isolation should be at least 84 hours for children with influenza A treated with
      oseltamivir and 108 hours for preschool children.

PMID- 16906399
TI  - Hypokalemic rhabdomyolysis in a child due to amphotericin B therapy.
AB  - Hypokalemia can result in life-threatening complications if not treated
      appropriately. Although hypokalemia is a frequent adverse effect of amphotericin
      B therapy, there are no reports in the pediatric literature on hypokalemia
      associated rhabdomyolysis induced by this drug. A ten-year-old boy with a history
      of one week amphotericin B treatment was admitted with weakness of the lower
      extremities, inability to walk and calf pain. Laboratory tests showed a serum
      potassium of 1.7 mEq/L and a serum creatinine phosphokinase of 3937 U/L plus
      myoglobulinuria. Following fluid expansion and intravenous potassium replacement,
      the patient progressed to achieve full regression of muscular weakness after one
      week. This report highlights hypokalemia as a rare cause of rhabdomyolysis.
      Patients on amphotericin B should be checked for this rare yet potentially life
      threatening complication.

PMID- 16906400
TI  - Menstrual cycle pattern during the first gynaecological years in girls with
      precocious puberty following gonadotropin-releasing hormone analogue treatment.

PMID- 16906401
TI  - [Transoral osteosynthesis of condylar neck fractures using a three-dimensional
      plate].
AB  - AIM: The transoral approach minimizes the risk of damaging the facial nerve.
      However, stable osteosynthesis with two miniplates at the proximal fragment is
      often not possible. To achieve a stable fixation also of condylar neck fractures
      a new delta-shaped plate was developed, which meets the biomechanical demands of
      this region. This plate was tested in a clinical study. PATIENTS AND METHODS: In
      total 11 patients suffering from 13 condyle fractures (Spiessl I: n=2, Spiessl
      II: n=10, Spiessl III: n=1, 3 bilateral fractures) were treated via a transoral
      approach and assessed clinically as well as radiologically in the follow-up
      period. Functional parameters and fracture alignment were assessed. RESULTS:
      After 6 months postoperative function had returned to normal with a mouth opening
      of 42 mm and pro- and laterotrusion of more than 5 mm. Postoperative radiographic
      controls showed a good fracture alignment in 7 of 8 patients respectively in 6 of
      8 cases after 6 months. In 12 of 13 fractures directly postoperative and in 10 of
      13 fractures 6 months postoperative, respectively, Towne's view radiographs
      showed an anatomical correct position. No plate fracture and no bending of plates
      were observed. Loosening of screws was found in 2 patients during plate removal.
      CONCLUSION: The newly developed three-dimensional plate was easy to handle, and a
      sufficiently stable osteosynthesis of condyle fractures was possible. This plate
      can be recommended for surgical fracture treatment via a transoral approach
      omitting extraoral scars and damage to the facial nerve.

PMID- 16906402
TI  - Prediction of cervical involvement in endometrial cancer by hysteroscopy.
AB  - OBJECTIVE: This study evaluated the ability of hysteroscopy to preoperatively
      predict cervical involvement in endometrial cancer. METHODS: The records of 110
      surgically staged consecutive endometrial cancer patients treated at our
      institution from 1997 to 2003 were retrospectively analyzed. Data on
      demographics, preoperative staging procedures, surgical pathology reports, and
      adjuvant treatments were retrieved. RESULTS: Fourteen (12.7%) patients had
      cervical involvement (stage II) according to the surgical pathology report, of
      whom nine (8.1%) had stage IIA and five (4.6%) had stage IIB. Clinical evaluation
      by speculoscopy and palpation had failed to reveal any indication of cervical
      involvement. Preoperative diagnostic hysteroscopy procedures were included. None
      of the hysteroscopy procedures revealed any suspicious lesion in the cervical
      canal. CONCLUSION: Hysteroscopy and clinical examination fail to adequately
      predict cervical involvement in endometrial carcinoma. Fractional D&C appears to
      be the best method until a more effective alternative becomes available.

PMID- 16906403
TI  - Primary amenorrhoea caused by congenital absence of the uterus.
AB  - The authors discuss the case of a 21-year-old female of Afro-Caribbean origin,
      who presented with primary amenorrhoea, and was found to have congenital absence
      of the uterus and fallopian tubes in the presence of a normal vaginal cavity.

PMID- 16906404
TI  - Continuous gluconic acid production by the yeast-like Aureobasidium pullulans in
      a cascading operation of two bioreactors.
AB  - The application of a new developed process for the continuous production of
      gluconic acid using a cascade of two bioreactors in a continuous process is shown
      reaching the highest concentration of gluconic acid described in the literature
      for continuous culture fermentation. Very high gluconic acid concentrations of
      272-308 g/l have been achieved under continuous cultivation of free-growing cells
      of Aureobasidium pullulans in the first bioreactor at residence times (RT)
      between 19.5 and 24 h with formation rates for the generic product between 12.7
      and 13.9 g/(l h). Gluconic acid, 350-370 g/l, was continuously reached in the
      second bioreactor at a total RT of 30.8-37 h with R (j) of 9.2-12 g/(l h). The
      highest specific gluconic acid production (m (p)) of 3.6 g/(g h) was found in the
      first bioreactor at the lowest RT of 19.5 h. The highest selectivity of 93.6% was
      determined in the first bioreactor as well. Complete glucose consumption was
      obtained at 37 h total residence time in the second bioreactor. Gluconic acid,
      433 g/l, was continuously produced in the second bioreactor at a total RT of 37
      h.

PMID- 16906405
TI  - Characterization of expressed Pgip genes in rice and wheat reveals similar extent
      of sequence variation to dicot PGIPs and identifies an active PGIP lacking an
      entire LRR repeat.
AB  - Polygalacturonase-inhibiting proteins (PGIPs) are leucine-rich repeat (LRR)
      proteins involved in plant defence. A number of PGIPs have been characterized
      from dicot species, whereas only a few data are available from monocots. Database
      searches and genome-specific cloning strategies allowed the identification of
      four rice (Oryza sativa L.) and two wheat (Triticum aestivum L.) Pgip genes. The
      rice Pgip genes (Ospgip1, Ospgip2, Ospgip3 and Ospgip4) are distributed over a 30
      kbp region of the short arm of chromosome 5, whereas the wheat Pgip genes,
      Tapgip1 and Tapgip2, are localized on the short arm of chromosome 7B and 7D,
      respectively. Deduced amino acid sequences show the typical LRR modular
      organization and a conserved distribution of the eight cysteines at the N- and C
      terminal regions. Sequence comparison suggests that monocot and dicot PGIPs form
      two separate clusters sharing about 40% identity and shows that this value is
      close to the extent of variability observed within each cluster. Gene-specific RT
      PCR and biochemical analyses demonstrate that both Ospgips and Tapgips are
      expressed in the whole plant or in a tissue-specific manner, and that OsPGIP1,
      lacking an entire LRR repeat, is an active inhibitor of fungal
      polygalacturonases. This last finding can contribute to define the molecular
      features of PG-PGIP interactions and highlights that the genetic events that can
      generate variability at the Pgip locus are not only limited to substitutions or
      small insertions/deletions, as so far reported, but can also involve variation in
      the number of LRRs.

PMID- 16906407
TI  - The acid tolerance response of Bacillus cereus ATCC14579 is dependent on culture
      pH, growth rate and intracellular pH.
AB  - The food pathogen Bacillus cereus is likely to encounter acidic environments (i)
      in food when organic acids are added for preservation purposes, and (ii) during
      the stomachal transit of aliments. In order to characterise the acid stress
      response of B. cereus ATCC14579, cells were grown in chemostat at different pH
      values (pH(o) from 9.0 to 5.5) and different growth rates (micro from 0.1 to 0.8
      h(-1)), and were submitted to acid shock at pH 4.0. Cells grown at low pH(o) were
      adapted to acid media and induced a significant acid tolerance response (ATR).
      The ATR induced was modulated by both pH(o) and micro, and the micro effect was
      more marked at pH(o) 5.5. Intracellular pH (pH(i)) was affected by both pH(o) and
      micro. At a pH(o) above 6, the pH(i) decreased with the decrease of pH(o) and the
      increase of micro. At pH(o) 5.5, pH(i) was higher compared to pH(o) 6.0,
      suggesting that mechanisms of pH(i) homeostasis were induced. The acid survival
      of B. cereus required protein neo-synthesis and the capacity of cells to maintain
      their pH(i) and DeltapH (pH(i) - pH(o)). Haemolysin BL and non-haemolytic
      enterotoxin production were both influenced by pH(o) and micro.

PMID- 16906406
TI  - Grouping of phenol hydroxylase and catechol 2,3-dioxygenase genes among phenol-
      and p-cresol-degrading Pseudomonas species and biotypes.
AB  - Phenol- and p-cresol-degrading pseudomonads isolated from phenol-polluted water
      were analysed by the sequences of a large subunit of multicomponent phenol
      hydroxylase (LmPH) and catechol 2,3-dioxygenase (C23O), as well as according to
      the structure of the plasmid-borne pheBA operon encoding catechol 1,2-dioxygenase
      and single component phenol hydoxylase. Comparison of the carA gene sequences
      (encodes the small subunit of carbamoylphosphate synthase) between the strains
      showed species- and biotype-specific phylogenetic grouping. LmPHs and C23Os
      clustered similarly in P. fluorescens biotype B, whereas in P. mendocina strains
      strong genetic heterogeneity became evident. P. fluorescens strains from biotypes
      C and F were shown to possess the pheBA operon, which was also detected in the
      majority of P. putida biotype B strains which use the ortho pathway for phenol
      degradation. Six strains forming a separate LmPH cluster were described as the
      first pseudomonads possessing the Mop type LmPHs. Two strains of this cluster
      possessed the genes for both single and multicomponent PHs, and two had genetic
      rearrangements in the pheBA operon leading to the deletion of the pheA gene. Our
      data suggest that few central routes for the degradation of phenolic compounds
      may emerge in bacteria as a result of the combination of genetically diverse
      catabolic genes.

PMID- 16906408
TI  - [Therapy for spontaneous intracerebral haemorrhage].
AB  - Spontaneous intracerebral haemorrhage (ICH) is a common and serious disease. It
      is responsible for 10-17% of all strokes, and mortality exceeds 50%. A variety of
      underlying causes exist for ICH, advancing age and hypertension being the most
      important risk factors. Other causes of ICH include vascular malformations,
      coagulation disorders, and use of anticoagulants and thrombolytic agents.
      Treatment options comprise conservative as well as surgical management. In
      addition, a recently published clinical trial evaluating the use of activated
      recombinant Factor VII allows specific haemostatic therapies to be used in ICH
      treatment. That and other studies have significantly added to the understanding
      of the disease. The European Stroke Initiative, which represents the European
      Stroke Council, European Neurological Society, and European Federation of
      Neurological Societies, will soon publish recommendations for the management of
      spontaneous intracerebral haemorrhages. Those recommendations form the basis of
      this article.

PMID- 16906409
TI  - ON- and OFF-response of the photopic electroretinogram in relation to stimulus
      characteristics.
AB  - The aim of this study was to explore the effect of stimulus duration, stimulus
      intensity, stimulus wavelength and background luminance on the amplitude and
      waveform of the ON- (b-wave) and OFF- (d-wave) response of the photopic ERG. The
      following parameters were used in this study: stimulus duration from 5 to 200 ms,
      the flash intensities from 0.4 to 2.1 log cd s/m2, the background luminance from
      20 to 50 cd/m2 and stimulus wavelengths 460, 508 and 667 nm. Prolonging the
      stimulus duration from 75 to 200 ms did not influence the amplitudes of a-, b-
      and d-waves significantly. Higher stimulus intensities (1.9 log cd s/m2)
      broadened the b-wave and increased variability of its implicit time. With a
      brighter background (50 cd/m2) the b-wave did not broaden and its optimal
      amplitude was preserved. Stimuli of longer wavelengths (667 nm) significantly
      reduced the d-wave amplitude. Our results suggest that high intensities and
      longer wavelengths (red) may not be suitable stimulus parameters in the routine
      clinical ON- and OFF-response recording.

PMID- 16906410
TI  - Osteoporosis associated with gyrate atrophy: a case report.
AB  - Gyrate atrophy (GA) is a rare degenerative, hereditary disease characterized by
      markedly high serum ornithine levels resulting from the deficiency of ornithine
      delta-amino transferase (OAT), a mitochondrial matrix enzyme. Hyperornithinaemia
      is accompanied by lysinuria and reduced lysine plasma levels in GA. Type I
      collagen is known to play a role in osteoporosis pathogenesis. Lysine has a role
      in cross ligament formation of type I collagen, a bone matrix element, and thus,
      in bone strength. Although the most common complaint in GA is visual problems,
      the disease may include muscle involvement, as well. Reduced physical activity
      resulting from muscle involvement and hypolysinemia in GA may lead to
      osteoporosis. However, there is no data in the literature concerning the relation
      between GA and osteoporosis. In this report a GA case with early osteoporosis,
      besides visual deterioration and muscular signs, is reported, and the relation
      between GA and osteoporosis is emphasized for the first time.

PMID- 16906411
TI  - Frequency doubling illusion VEPs and automated perimetry in multiple sclerosis.
AB  - We examined frequency doubling (FD) illusion based automated perimetry (FDT) and
      dichoptic FD multifocal visual evoked potentials (FDmfVEPs) in Normal and
      multiple sclerosis (MS) subjects. Contrast thresholds were determined at 17
      visual field locations using an FDT perimeter. The stimuli presented to each
      location were 0.25 cpd gratings presented with rapid (25 Hz) counterphase flicker
      and thus displayed the spatial FD illusion. Dichoptic mfVEPs were recorded by
      concurrently stimulating eight regions/eye with FD stimuli presented at 95%
      contrast. Recordings were obtained from 27 Normal subjects, 26 MS patients who
      had experienced Optic Neuritis (MSON) and 24 MS patients without a history of ON
      (MSNON). The FDT thresholds showed enhanced contrast sensitivity for MSON
      patients (P < 0.0001) but not for MSNON patients. Response amplitudes for the
      central four regions of the mfVEP stimulus were reduced in both patient groups (P
      < 0.005). A classification model based upon the FDT thresholds performed at a
      specificity of 96% for a sensitivity of 97% in MSON patients, but the accuracy
      (simultaneously largest sensitivities and specificities) was poor (approximately
      60%) in MSNON patients. Discriminant models based on the FDT thresholds and
      FDmfVEPs were able to diagnose more that 90% MSON patients but performed poorly
      for MSNON patients.

PMID- 16906412
TI  - Congenital absence of optic chiasm: demonstration of an uncrossed visual pathway
      using monocular flash visual evoked potentials.
AB  - A 35 month old child was referred for electrophysiology testing with pendular
      nystagmus, corresponding head oscillations and reduced vision. Flash visual
      evoked potential (VEP) revealed large responses at the right occiput (but not the
      left occiput) from the right eye and similar large responses at only the left
      occiput from the left eye, indicating absent/deficient crossover at the chiasm. A
      magnetic resonance imaging (MRI) scan subsequently confirmed absence of the optic
      chiasm. There was no other evidence of midline brain defects. Her subsequent
      development to age 11 has been followed. The nystagmus has remained mainly
      horizontal but a torsional component was noted from age 5 years and described as
      see-saw at age 6 years. A small right esotropia was noted at 6 years and
      spectacles prescribed for low hypermetropic refractive error. Bilateral superior
      rectus recessions at age 7 years produced an improved head posture. Her visual
      acuity has remained stable at around 6/24 from age 4 years. No binocularity nor
      stereopsis has been demonstrated over subsequent visits.

PMID- 16906413
TI  - Comparative polytene chromosome maps of D. montana and D. virilis.
AB  - Chromosomal inversion polymorphism was characterized in Finnish Drosophila
      montana populations. A total of 14 polymorphic inversions were observed in
      Finnish D. montana of which nine had not been described before. The number of
      polymorphic inversions in each chromosome was not significantly different from
      that expected, assuming equal chance of occurrence in the euchromatic genome.
      There was, however, no correlation between the number of polymorphic inversions
      and that of fixed inversions in each chromosome. Therefore, a simple neutral
      model does not explain the evolutionary dynamics of inversions. Furthermore, in
      contrast to results obtained by others, no significant correlation was found
      between the two transposable elements (TEs) Penelope and Ulysses and inversion
      breakpoints in D. montana. This result suggests that these TEs were not involved
      in the creation of the polymorphic inversions seen in D. montana. A comparative
      analysis of D. montana and Drosophila virilis polytene chromosomes 4 and 5 was
      performed with D. virilis bacteriophage P1 clones, thus completing the
      comparative studies of the two species.

PMID- 16906414
TI  - Effects of endurance training on intracellular calcium concentration in T
      lymphocytes.
AB  - The purpose of the present study was to determine whether 12 months of endurance
      training reduced [Ca2+]i in T helper (CD4+) lymphocytes in trained (TR) men
      compared to untrained (UT). Fourteen trained (Ironman triathletes) and nine
      untrained (sedentary) men volunteered for the study. The TR group averaged 12 km
      of swimming, 300 km of cycling and 60 km of running per week during the year.
      Resting blood samples were taken from TR (VO(2peak) 64 +/- 2 ml kg(-1) min(-1))
      and UT (VO(2peak) 42 +/- 2 ml kg(-1) min(-1)) subjects every 4 weeks for 52 weeks
      (October 1, 1999-October 1, 2000). Leukocyte concentration was measured using a
      full blood count. Unstimulated CD4+ lymphocytes were separated and analysed for
      changes in free ([Ca2+]i) and total ([Ca2+]t) calcium using flow cytometry. There
      were no significant differences in leukocyte concentration between UT and TR
      groups. There were significant differences between TR and UT in [Ca2+]i (October
      B and November), and [Ca2+]t (January and March). There were also significant
      sequential monthly changes in both [Ca2+]i and [Ca2+]t for TR and UT groups
      during the study. Significant increases in [Ca2+]i and [Ca2+]t during summer
      (January and March) for both TR and UT groups suggest an increase in
      intracellular signalling during hot weather. [Ca2+]i and [Ca2+]t were
      significantly lower in TR lymphocytes during November and March, suggesting that
      endurance training during warmer months may decrease [Ca2+]i through altered
      intracellular signalling, possibly to maintain lymphocyte function during heat
      stress.

PMID- 16906415
TI  - Performance following prolonged sub-maximal cycling at optimal versus freely
      chosen pedal rate.
AB  - It was tested whether cyclists perform better during all-out cycling following
      prolonged cycling at the pedal rate resulting in minimum oxygen uptake (VO(2)),
      i.e. the energetically optimal pedal rate (OPR) rather than at the freely chosen
      pedal rate (FCPR). Nine trained cyclists cycled at 180 W to determine individual
      OPR and FCPR. Baseline performance was determined by measuring mean power output
      (W(5min)) and peak VO(2) during 5-min all-out cycling at FCPR. Subsequently, on
      two separate days, the cyclists cycled 2.5 h at 180 W at OPR and FCPR, with each
      bout followed by a 5-min all-out trial. FCPR was higher (P < 0.05) than OPR at
      180 W (95 +/- 7 and 73 +/- 11 rpm, respectively). During the prolonged cycling,
      VO(2), heart rate (HR), and rate of perceived exertion (RPE) were 7-9% higher (P
      < 0.05) at FCPR than at OPR and increased (P < 0.05) 2-21% over time. During all
      out cycling following prolonged cycling at OPR and FCPR, W(5min) was 8 and 10%
      lower (P < 0.05) than at baseline, respectively. Peak VO(2) was lower (P < 0.05)
      than at baseline only after FCPR. The all-out trial power output was reduced
      following 2.5 h of cycling at 180 W at both OPR and FCPR. However, this aspect of
      performance was similar between the two pedal rates, despite a higher
      physiological load (i.e. VO(2), HR, and RPE) at FCPR during prolonged cycling.
      Still, a reduced peak VO(2) only occurred after cycling at FCPR. Therefore,
      during prolonged sub-maximal cycling, OPR is at least as advantageous as FCPR for
      performance optimization in subsequent all-out cycling.

PMID- 16906416
TI  - [The influence of the T stage on the risk of metastasis of penis cancer: T1 vs.
      T2].
AB  - BACKGROUND: Controversies persist over the therapeutic approach to T1 penile
      carcinoma, particularly in patients with negative inguinal lymph nodes. Available
      data on lymph nodes metastases (LNM) in T1 carcinoma are contradictory. The aim
      of this study was to evaluate the metastatic risk of T1 carcinoma and to compare
      it with that of T2 carcinoma. MATERIAL AND METHODS: A total of 37 patients (pts)
      with T1 or T2 tumors were reviewed. Assessment of the inguinal lymph node
      condition was based on node dissection in 29 pts and surveillance in eight pts
      (mean 62 months, range 22-162). RESULTS: Grading was classified as good (G1),
      moderate (G2) and poor (G3) in seven, 26 and four pts, respectively. Tumor stage
      was T1 in 21 and T2 in 16 pts. LNM were observed in eight of 21 T1 (38%) and six
      of 16 T2 tumors (38%). No G1 and all G3 tumors developed LNM independently of
      tumor stage. Ten of the 26 G2 carcinomas (38%) harboured LNM and seven of these
      pts (70%) had a T1 tumor. CONCLUSIONS: According to our data, the metastatic
      potential of T1 penile carcinoma has been underestimated in the recent
      literature. Tumor grading has a substantially stronger impact on the metastatic
      risk in T1 and T2 penile carcinoma than tumor stage, indicating a surgical lymph
      node staging starting at the pT1G2 stage.

PMID- 16906417
TI  - [Penetrating injuries to the pelvis].
AB  - As criminality and weapon use increase, general and military surgeons are
      increasingly confronted with penetrating pelvic injuries both at home and on
      peacekeeping missions. Penetrating injuries to the iliac vascular axis are
      associated with considerable mortality, and thus the majority of these emergency
      patients arrive in a state of deep hypovolemic shock. Concomitant bowel injuries
      are present in one of five cases, resulting in contamination of the damaged area.
      Surgical options are simple lateral repair, ligation of the veins, temporary
      shunt insertion, and prosthetic graft interposition in the injured artery. In
      extremis ligation of the common or external iliac artery may be the only option
      to save the patient's life. Surgeons must be aware that damage control surgery
      and related methods may be needed early on to enable patient survival.

PMID- 16906419
TI  - Adult bone-marrow-derived mesenchymal stem cells contribute to wound healing of
      skin appendages.
AB  - Adult bone-marrow-derived mesenchymal stem cells (MSCs) are well-established as
      having the capacity to differentiate into cells with mesodermal, ectodermal, and
      endodermal characteristics and can leave their niche to home toward and engraft
      within foreign tissues. To investigate whether adult MSCs contribute to the
      repair of skin appendages after injury, BrdU-labeled MSCs were co-cultured with
      heat-shocked confluent sweat gland cells (SGCs) in vitro and later intravenously
      injected into full-thickness skin wounds in rats. When adult MSCs were co
      cultured with heat-shocked SGCs, a subset of adult MSCs differentiated into SGCs,
      the percentage of differentiation being enhanced by epidermal growth factor and
      the injured microenviroment, but weakened by PD98059. The ERK (extracellular
      signal-regulated kinase) pathway, especially pERK, was involved in the phenotype
      conversion of human MSCs into human SGC. Labeled MSCs were noted in hair
      follicles, sebaceous glands, blood vessels, and dermis in full-thickness wounds,
      and the incorporated cells in hair follicles and sebaceous glands were also
      positive for pan-cytokeratin. After wound healing, some labeled MSCs returned to
      the bone marrow, whereas other were retained in the dermis. We conclude that
      adult MSCs have the capacity to dock at specific sites, to contribute to wound
      healing of skin appendages, and to home toward marrow, and that engraftment of
      bone-marrow-derived cells is a functional event.

PMID- 16906418
TI  - Overexpression of human 27 kDa heat shock protein in laryngeal cancer cells
      confers chemoresistance associated with cell growth delay.
AB  - PURPOSE: Among the family of heat shock proteins (HSPs), HSP70 and HSP27 have
      been implicated in tumorigenesis and chemoresistance, probably via the prevention
      of apoptosis. HSP27 levels are frequently increased in large populations of
      tumors of the head and neck, but the mechanism of its chemoresistance is not yet
      fully understood. In the present study, the role of HSP27 in the resistance to
      cytotoxic stress was studied in Hep-2 human laryngeal cancer cells. METHOD: We
      established a Hep-2 cell line overexpressing HSP27 and examined whether the
      expression of HSP27 provides resistance to heat shock and several cytotoxic
      agents using a MTT colorimetic assay. Cell cycle progression was assessed by flow
      cytometry and fluorescence staining was performed for F-actin filaments. RESULTS:
      HSP27 overexpression induced cellular resistance to heat shock at 45 degrees C
      for 1 h as well as against several cytotoxic agents, including cisplatin,
      staurosporin and H(2)O(2). However, no difference in sensitivity to irradiation
      or serum starvation was found. Moreover, HSP27 overexpressing Hep-2 cells showed
      a delayed cell growth, compared to control cells. To determine if the decreased
      cell proliferation in HSP27 overexpressing cells contributed to chemoresistance,
      control Hep-2 cells were synchronized at the late G1 phase by treatment with
      mimosine. The synchronized Hep-2 cells were resistant to cisplatin and H(2)O(2),
      but not to irradiation or serum starvation, correlating the protection effect
      shown in HSP27 overexpressing cells. These results suggest that the
      overexpression of HSP27 in Hep-2 cells confers chemoresistance which is
      associated with the delay in cell growth. We also propose that the stabilization
      of F-actin observed in Hep-2/hsp27 cells is partly related to the delay in cell
      cycle progression, by showing that the induction of actin polymerization in Hep
      2/neo cells results in the retardation of cell growth as well as a cytoprotective
      effect as observed in Hep-2/hsp27.

PMID- 16906420
TI  - Centrosome inheritance in the parthenogenetic egg of the collembolan Folsomia
      candida.
AB  - Unfertilized eggs commonly lack centrioles, which are usually provided by the
      male gamete at fertilization, and are unable to assemble functional reproducing
      centrosomes. However, some insect species lay eggs that develop to adulthood
      without a contribution from sperm. We report that the oocyte of the
      parthenogenetic collembolan Folsomia candida is able to self-assemble microtubule
      based asters in the absence of pre-existing maternal centrosomes. The asters,
      which develop near the innermost pole of the meiotic apparatus, interact with the
      female chromatin to form the first mitotic spindle. The appearance of microtubule
      based asters in the cytoplasm of the activated Folsomia oocyte might represent a
      conserved mechanism for centrosome formation during insect parthenogenesis. We
      also report that the architecture of the female meiotic apparatus and the
      structure of the mitotic spindles during the early embryonic divisions are
      unusual in comparison with that of insects.

PMID- 16906421
TI  - Expression of glutamic acid decarboxylase and identification of GABAergic cells
      in the ischemic rat dentate gyrus.
AB  - We have investigated the glutamic acid dexcarboxylase (GAD) mRNA and protein
      isoforms as markers for ischemic loss of GABAergic neurons in the dentate hilus.
      Stereological counts of these neurons were performed in rats surviving 8 days
      after 10 min of transient forebrain ischemia, and in control rats (sham-operated
      and naive). GAD65 and GAD67 were detected by both in situ hybridization and
      immunocytochemistry. No differences (three-way ANOVA, P > 0.05) were found
      between treatments (ischemia, sham-operated or naive) when cell counts of
      identical GAD isoforms were compared at the same level (mRNA or protein).
      However, irrespective of treatments, the number of neurons expressing GAD65 mRNA
      was significantly higher than the number of neurons expressing GAD65 protein, and
      the number of neurons expressing GAD67 mRNA was significantly lower than the
      number of neurons expressing GAD67 protein. In parallel, we investigated the
      colocalization of the cell death marker Fluorojade B (FJB) with somatostatin- or
      GAD67-immunoreactivity in hilus of control and ischemic rats. Although the
      majority of FJB positive cells also contained somatostatin, a small number of
      GAD67 immunoreactive neurons contained FJB, suggesting that a small number of
      GABAergic neurons die after ischemia. In conclusion, this study provides direct
      evidence that a small proportion of GABAergic hilar neurons succumbs to ischemia.
      Stereological counts of neurons identified from their expression of either GAD
      isoform of mRNA or protein revealed a high inter-animal variation at any
      detection level in both naive, sham-operated and ischemic rats. Therefore, counts
      of GABAergic neurons should be carefully interpreted in accordance with the
      marker used for identification.

PMID- 16906422
TI  - Successful joint arthroplasty after treatment of destructive MRSA arthritis of
      the knee using antibiotic-loaded hydroxyapatite blocks: a case report.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) septic arthritis is frequently
      associated with a poor clinical outcome. Joint reconstruction may be worth
      attempting in patients with a history of persistent MRSA infection. Here we
      report an unusual case of MRSA septic arthritis of the knee joint that was
      treated successfully by joint replacement after initial placement of antibiotic
      loaded hydroxyapatite (HA) blocks.

PMID- 16906423
TI  - Osteochondroma of C7 vertebra presenting as compressive myelopathy in a patient
      with nonhereditary (nonfamilial/sporadic) multiple exostoses.
AB  - INTRODUCTION: Osteochondromas are most commonly found in the appendicular
      skeleton. They occur less frequently in the spine and compression of the spinal
      cord is very rare. To the best of our knowledge, this is the first report of an
      osteochondroma arising from C7 vertebra presenting with compressive myelopathy in
      a patient with nonhereditary multiple exostoses. Our purpose is to report this
      rare presentation and its successful management, and to highlight the clinico
      radiological features of this treatable condition. MATERIALS AND METHODS: A 20
      year-old male with nonhereditary exostoses presented with gradual onset weakness
      in bilateral lower limbs, which had rapidly progressed to complete paraplegia
      over 1 month. The tumor was effectively treated by surgical excision along with
      spinal decompression. The diagnosis was confirmed by histopathological evidence
      complemented by clinico-radiological studies. RESULTS: There has been a complete
      functional recovery without any evidence of recurrence at last follow-up at 2
      years. CONCLUSION: Compressive myelopathy due to an osteochondroma arising from
      C7 vertebra in a case with nonhereditary multiple exostoses is being reported for
      the first time. Both CT and MRI demonstrated the origin, size, extent and
      relationship of the tumor to the vertebral and neural elements. Complete recovery
      of functions after surgical decompression was achieved in this case. An
      osteochondroma of spine must always be considered in all patients with multiple
      exostoses who have spine pain or develop neural deficit.

PMID- 16906424
TI  - Rapid rehabilitation programme following sacral stress fracture in a long
      distance running female athlete.
AB  - Stress fractures occur in normal bone due to mechanical overload by cyclic stress
      increasing the osteoclastic activity, thus facilitating weakening leading to
      fracture of bones. Long-distance running may lead to stress fractures of the mid-
      and distal tibia and of the metatarsal bones. Stress fractures to the sacrum are
      rare. Certain factors for stress fractures in runners have been identified, such
      as leg-length inequality, a high longitudinal arch of the foot, forefoot varus,
      and menstrual irregularities in case of female athlete triad. We report on a 22
      year-old female runner (usually training 140 km/week) suffering a sacral fatigue
      type fracture. The female athlete triad with eating disorders, dysmenorrhea, and
      osteopenia was ruled out. Sexual hormone blood samples proofed normal values. The
      diagnosis was performed using magnetic resonance imaging 2 weeks after the onset
      of buttock pain. A conservative treatment regimen was initiated with strict
      physical rest for the first 2 weeks, and then gradual increase of physical
      activity with 60-90 min of daily cycling and moderate 2 x 60 min cross-training.
      After another 2 weeks time, daily 60-90 min of walking, Nordic pole walking, and
      moderate strength training two times a week was performed. At 7 weeks running was
      started, gradually increased to 90 km/week without any pain. A rapid
      rehabilitation programme after sacral stress fractures involving low impact
      physical activity, such as Walking and Nordic pole walking, is applicable to
      female athletes after ruling out the female athlete triad.

PMID- 16906425
TI  - Glucose uptake inhibitor sensitizes cancer cells to daunorubicin and overcomes
      drug resistance in hypoxia.
AB  - PURPOSE: A high-rate glycolysis is a fundamental property of solid tumors and is
      associated with an over-expression of glucose transporters and glycolytic
      enzymes. We hypothesize that over-expression of glucose transporters in tumors
      prevents apoptosis, promotes cancer cell survival, and confers drug resistance.
      Inhibition of glucose transporter will preferentially sensitize the anticancer
      effects of chemotherapeutic drugs to overcome drug resistance in hypoxia.
      METHODS: Glucose transporter expressions were detected in cancer tissues and NCI
      60 cancer cells with immunostaining and DNA microarray. Glucose uptake was
      measured with 3H-2-deoxy-glucose. Cytotoxicity of daunorubicin (DNR) in
      combination of glucose inhibitor was detected by MTS assay under hypoxic
      condition. Early stage apoptosis was monitored with Annexin V-FITC staining.
      RESULTS: Immunostaining showed that GLUT1 was significantly increased in hypoxic
      regions of the human colon and breast tumors. The expression profiles of all
      glucose transporters in NCI 60 cancer cells exhibited distinct expression
      patterns. Phloretin exhibited more than 60% glucose uptake inhibition. Hypoxia
      conferred two to fivefold higher drug resistance in SW620 and K562 to DNR.
      Inhibition of glucose uptake by phloretin sensitized cancer cells to DNR for its
      anticancer activity and apoptosis to overcome drug resistance only under hypoxia.
      CONCLUSION: Cancer cells heavily rely on glucose transporters for glucose uptake
      to facilitate a high-rate glycolysis under hypoxia for their survival and drug
      resistance. Combination of glucose transporter inhibitors and chemotherapeutic
      drugs may provide a preferential novel therapeutic strategy to overcome drug
      resistance in hypoxia.

PMID- 16906427
TI  - [Equipment of a land-based emergency medical service in Bavaria: a
      questionnaire].
AB  - BACKGROUND: Currently valid DIN regulations concerning the emergency equipment in
      physician-staffed rescue vehicles are not well defined for every single item.
      This leads to variations in the equipment in different ambulances. The aim of
      this study was to demonstrate the differences with some exemplary equipment
      purchases. METHODS: All 218 physician-staffed rescue vehicles in Bavaria received
      a questionnaire asking for current emergency medical equipment and planned items.
      RESULTS: A reply was received from 177 of the 218 bases (81%). The main results
      were that 88% of all bases had a 12-lead ECG, a portable emergency ventilator was
      available at 93% of all bases, 77% had alternative airway management devices (set
      for emergency coniotomy 71%, laryngeal mask 26%), expiratory CO(2 )measuring was
      available at 32% and 31 bases (18%) had fibrinolytic drugs in the emergency
      vehicles. CONCLUSIONS: There are vast differences among the emergency physician
      staffed ambulances concerning the equipment which means that medical treatment
      according to current recommendations is not always possible at all bases.

PMID- 16906428
TI  - Condition-dependent dispersal of a patchily distributed riparian ground beetle in
      response to disturbance.
AB  - In common with many habitat elements of riverine landscapes, exposed riverine
      sediments (ERS) are highly disturbed, naturally patchy and regularly distributed,
      whose specialists are strongly adapted to flood disturbance and loss of habitat
      due to succession. Investigations of dispersal in ERS habitats therefore provide
      an important contrast to the unnaturally fragmented, stable systems usually
      studied. The present investigation analysed the three interdependent stages of
      dispersal: (1) emigration, (2) inter-patch movement and (3) immigration of a
      common ERS specialised beetle, Bembidion atrocaeruleum (Stephens 1828)
      (Coleoptera, Carabidae), in a relatively unmodified section of river, using mark
      resight methods. Dispersal was correlated with estimates of local population size
      and density, water level and patch quality in order to test for condition
      dependent dispersal cues. Flood inundation of habitat was found to increase
      strongly the overall rate of dispersal, and the rate of emigration was
      significantly higher from patches that were heavily trampled by cattle. Strongly
      declining numbers of dispersers with distance suggested low dispersal rates
      during periods of low water level. Dispersal in response to habitat degradation
      by cattle trampling would likely lead to a higher overall population fitness than
      a random dispersal strategy. Dispersal distances were probably adapted to the
      underlying habitat landscape distribution, high-flow dispersal cues and ready
      means of long-distance dispersal through hydrochory. Species whose dispersal is
      adapted to the natural habitat distribution of riverine landscapes are likely to
      be strongly negatively affected by reduced flood frequency and intensity and
      habitat fragmentation through flow regulation or channelisation.

PMID- 16906429
TI  - Thorax ultrasound in the management of pediatric pneumonias complicated with
      empyema.
AB  - The aim of this work is to prospectively study the value of thoracic ultrasound
      (US) before pleural drainage in children with parapneumonic effusion (PPE). All
      children hospitalized for PPE, identified by thoracic radiography, underwent US
      to assess pleural loculation, echogenicity, and pleural fluid quantity. From
      August 2001 to July 2003, 52 children were examined. US was performed on 48 of
      these children, of whom 35 received chest tube drainage and 13 only received
      clinical treatment. US identified 38 patients with free flowing and 10 with
      loculated pleural fluid. About 25 of the free flowing (65.8%) and 10 (100%) of
      the loculated patients received chest tube drainage. Echogenicity was anechoic in
      13, echoic without septations in 17 and echoic with septations in 18. Chest tube
      drainage was required in 6 anechoic (46.15%), 14 echoic without septations
      (82.35%), and 15 echoic with septations (83.33%). Quantity of fluid estimated by
      US varied from 20 to 860 ml. Effusion volume was higher in patients that were
      echoic with septations and loculated effusions. Pleural glucose and pH were
      lower, and LDH was higher in loculated PPE patients. In conclusion, US is an
      auxiliary exam for determining whether thoracic drainage is needed in
      parapneumonic effusion; loculated or echoic effusion should be drained, and free
      anechoic fluid needs further investigation.

PMID- 16906426
TI  - Staging of Alzheimer disease-associated neurofibrillary pathology using paraffin
      sections and immunocytochemistry.
AB  - Assessment of Alzheimer's disease (AD)-related neurofibrillary pathology requires
      a procedure that permits a sufficient differentiation between initial,
      intermediate, and late stages. The gradual deposition of a hyperphosphorylated
      tau protein within select neuronal types in specific nuclei or areas is central
      to the disease process. The staging of AD-related neurofibrillary pathology
      originally described in 1991 was performed on unconventionally thick sections
      (100 mum) using a modern silver technique and reflected the progress of the
      disease process based chiefly on the topographic expansion of the lesions. To
      better meet the demands of routine laboratories this procedure is revised here by
      adapting tissue selection and processing to the needs of paraffin-embedded
      sections (5-15 mum) and by introducing a robust immunoreaction (AT8) for
      hyperphosphorylated tau protein that can be processed on an automated basis. It
      is anticipated that this revised methodological protocol will enable a more
      uniform application of the staging procedure.

PMID- 16906430
TI  - Is hernial sac removal necessary? Retrospective evaluation of eight patients with
      Morgagni hernia in 5 years.
AB  - Eight children with Morgagni hernia were operated between January 2000 and May
      2005. Medical records of the patients were evaluated retrospectively. Ages of the
      patients were between 3.5 months and 9 years. The diaphragmatic defect was on the
      right in all patients except one. One patient had bilateral diapragmatic hernia.
      All of the patients were operated by abdominal approach. All patients had hernial
      sacs. During operation sac of hernia was everted to peritoneal space without
      removal and the defect was closed by using nonabsorbable material. There was no
      intraoperative complication. The patients were discharged on the sixth day in
      uneventful condition. There was no complication or recurrence during follow up.
      Excision of sac of hernia is recommended in majority. Most of the published
      studies favour the removal of hernial sac. In our practise, in the treatment of
      Morgagni hernia we did not remove the hernia sac during the last 5 years.

PMID- 16906432
TI  - Rotating wave solutions of the FitzHugh-Nagumo equations.
AB  - This paper will treat the bifurcation and numerical simulation of rotating wave
      (RW) solutions of the FitzHugh-Nagumo (FHN) equations. These equations are often
      used as a simple mathematical model of excitable media. The dependence of the
      solutions on a uniformly applied current, and also on the diffusion coefficients
      or domain size will be studied. Ranges of applied current and/or diffusion
      coefficients in which RW solutions are observed will be described using
      bifurcation theory and continuation methods. The bifurcation of time-periodic
      solutions of these FHN equations without diffusion is described first. Similar
      methods are then used to find RW solutions on a circular ring and numerical
      simulations are described. These results are then extended to investigate RW
      solutions on annular rings of finite cross-section. Scaling arguments are used to
      show how the existence of solutions depends on either the diffusion coefficient
      or on the size of the region.

PMID- 16906431
TI  - Analysis of contrast-enhanced MR images to assess renal function.
AB  - The image analysis and kinetic modeling methods used in dynamic contrast-enhanced
      magnetic resonance imaging of the kidney are reviewed. Image analysis includes
      various techniques of coregistration and segmentation. Few methods have been
      completely implemented. Nevertheless, the use of coregistration may become a
      standard to decrease the effect of motion on abdominal images and improve the
      quality of the renal signals. Kinetic models are classified into three
      categories: enhancement-based, external and internal representations. Enhancement
      based representations are limited to a basic analysis of the tracer concentration
      curves in the kidneys. Their relationship to the underlying physiology is complex
      and undefined. However, they can be used to evaluate the split renal function.
      External representations assess the kidney input and output. An external
      representation based on the up-slope of the renal enhancement to calculate the
      renal perfusion is commonly used because of its simplicity. In contrast, external
      representation based on deconvolution or identification methods remain
      underexploited. For glomerular filtration, an internal representation based on a
      two-compartmental model is mostly used. Internal representations based on multi
      compartmental models describe the renal function in a more realistic way. Because
      of their numerical complexity, these models remain rarely used.

PMID- 16906433
TI  - Glyphosate, paraquat and ACCase multiple herbicide resistance evolved in a Lolium
      rigidum biotype.
AB  - Glyphosate is the world's most widely used herbicide. A potential substitute for
      glyphosate in some use patterns is the herbicide paraquat. Following many years
      of successful use, neither glyphosate nor paraquat could control a biotype of the
      widespread annual ryegrass (Lolium rigidum), and here the world's first case of
      multiple resistance to glyphosate and paraquat is confirmed. Dose-response
      experiments established that the glyphosate rate causing 50% mortality (LD(50))
      for the resistant (R) biotype is 14 times greater than for the susceptible (S)
      biotype. Similarly, the paraquat LD(50 )for the R biotype is 32 times greater
      than for the S biotype. Thus, based on the LD(50 )R/S ratio, this R biotype of L.
      rigidum is 14-fold resistant to glyphosate and 32-fold resistant to paraquat.
      This R biotype also has evolved resistance to the acetyl-coenzyme A carboxylase
      (ACCase) inhibiting herbicides. The mechanism of paraquat resistance in this
      biotype was determined as restricted paraquat translocation. Resistance to ACCase
      inhibiting herbicides was determined as due to an insensitive ACCase. Two
      mechanisms endowing glyphosate resistance were established: firstly, a point
      mutation in the 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) gene,
      resulting in an amino acid substitution of proline to alanine at position 106;
      secondly, reduced glyphosate translocation was found in this R biotype,
      indicating a co-occurrence of two distinct glyphosate resistance mechanisms
      within the R population. In total, this R biotype displays at least four co
      existing resistance mechanisms, endowing multiple resistance to glyphosate,
      paraquat and ACCase herbicides. This alarming case in the history of herbicide
      resistance evolution represents a serious challenge for the sustainable use of
      the precious agrochemical resources such as glyphosate and paraquat.

PMID- 16906435
TI  - Polycyclic aromatic hydrocarbon (PAH) metabolizing enzyme activities in human
      lung, and their inducibility by exposure to naphthalene, phenanthrene, pyrene,
      chrysene, and benzo(a)pyrene as shown in the rat lung and liver.
AB  - In order to survey changes and activities in the polycyclic aromatic hydrocarbon
      (PAH)-metabolizing enzymes implicated in lung cancer susceptibility studies, we
      investigated enzyme induction by 2-5-ring-sized 'biomarker' PAHs in rat liver and
      lung, and the activities in five human lung specimens. Naphthalene, phenanthrene,
      pyrene, chrysene, and benzo[a]pyrene (BaP) were administered to rats for 3 days
      (25-128 mg/kg/day) and the responses compared with those of model inducers. PAH
      treatment increased the CYP1A-catalyzed activity of pyrene 1-hydroxylation and 7
      ethoxyresorufin O-deethylation in rat liver by up to 28- and 279-fold, and in rat
      lung by up to 22- and 51-fold, respectively. 1-Naphthol (hUGT1A6), 1
      hydroxypyrene (hUGT1A6/1A9), and entacapone (hUGT1A9) are markers of PAH
      glucuronidating human uridine diphosphate-glucuronosyltransferases (UGT). These
      activities increased up to 6.4-fold in rat liver and up to 1.9-fold in rat lung.
      NADPH:quinone oxidoreductase 1 (NQO1) and glutathione S-transferase activities
      increased up to 5.3- and 1.6-fold (liver), and up to 4.4- and 1.4-fold (lung),
      respectively. CYP1A showed the best liver-to-lung relationship (R (2 )=( )0.90).
      The inducing efficiency by PAHs differed extensively: control <or= naphthalene <
      phenanthrene, pyrene << chrysene < BaP. In human lung (non-smokers), the marker
      activities of CYP1A1, UGT1A6/1A9, and NQO1 were lower than those in rat lung.
      Epoxide hydrolase activity was 1,000-fold higher than the pulmonary CYP1A1
      activities. Human UGT and NQO1 displayed large variations (>60-fold), many times
      greater than the experimental (inducible/constitutive) variation in the rat.
      Kinetics of 1-hydroxypyrene glucuronidation showed two low-K (m) forms both in
      rat and human lung. Since the 2-4-ring PAHs (major constituents) were poor enzyme
      inducers, it appears that the PAH-metabolizing pathways are mainly induced by BaP
      type minor constituents. Gene-environmental interactions which magnify
      polymorphic variability in pulmonary bioactivation/detoxification capacity
      probably play a key role in individual susceptibility to (or protection against)
      chemically induced lung cancer. Hence, human exposure to PAH mixtures with high
      content of BaP-type hydrocarbons confers a potentially higher health risk than
      PAH mixtures with low content of procarcinogens.

PMID- 16906434
TI  - Brassinosteroid confers tolerance in Arabidopsis thaliana and Brassica napus to a
      range of abiotic stresses.
AB  - In addition to an essential role in plant development, brassinosteroids (BRs)
      appear to have the ability to protect plants against various environmental
      stresses. However, studies confirming the ability of BRs to modulate plant
      responses to different environmental stresses are lacking. Earlier we had
      demonstrated that treatment with 24-epibrassinolide (EBR), a BR, increases the
      basic thermotolerance of Brassica napus and tomato seedlings [Plant Mol Biol
      40:333-342, 1999]. Here we demonstrate that EBR treatment enhances seedling
      tolerance to drought and cold stresses in both Arabidopsis thaliana and B. napus,
      and helps to overcome a salt-stress-induced inhibition of seed germination. The
      ability of EBR to confer tolerance in plants to a variety of stresses was
      confirmed through analysis of expression of a subset of drought and cold stress
      marker genes. Transcriptional changes in these genes were more apparent in EBR
      treated A. thaliana, in particular during earlier time points of stress. To see
      if BR is essential for the heat stress (HS) response, we made use of BR-deficient
      mutants. Both det2-1 and dwf4 mutants still expressed heat shock proteins (hsps)
      to high levels during HS, indicating that although BR augments thermotolerance in
      plants, it is not necessary for hsp expression during HS.

PMID- 16906436
TI  - Effects of uniaxial cyclic strain on adipose-derived stem cell morphology,
      proliferation, and differentiation.
AB  - Cells and tissues in vivo are subjected to various forms of mechanical forces
      that are essential to their normal development and functions. The arterial blood
      vessel wall is continuously exposed to mechanical stresses such as pressure,
      strain, and shear due to the pulsatile nature of blood flow. Vascular smooth
      muscle cells (SMCs) populate the media of blood vessels and play important roles
      in the control of vasoactivity and the remodeling of the vessel wall. It is well
      documented that the phenotype and functions of vascular SMCs are not only
      regulated by chemical factors such as transforming growth factor-beta(1) (TGF
      beta(1)), but also by mechanical factors such as uniaxial strain. The purpose of
      our study was to explore the effects of TGF-beta(1) alone or in combination with
      uniaxial cyclic strain on adipose-derived stem cell (ASC) morphology,
      proliferation, and differentiation. Low passage ASCs were stimulated with 10%
      strain at 1 Hz for 7 days, with or without TGF-beta(1). Cyclic strain inhibited
      proliferation, and caused alignment of the cells and of the F-actin cytoskeleton
      perpendicular to the direction of strain. Strain alone resulted in a decrease in
      the expression of early SMC markers alpha-SMA and h (1)-calponin. While the
      response of SMCs and other progenitor cells such as bone marrow stromal cells to
      mechanical forces has been extensively studied, the roles of these forces on ASCs
      remain unexplored. This work advances our understanding of the mechanical
      regulation of ASCs.

PMID- 16906438
TI  - A quick-solidifying, coloured silicone mixture for injecting into brains for
      autopsy: technical report.
AB  - The injection of cadaver brains is invaluable for anatomic study, but cadavers
      that have been properly handled are not easy to obtain. A large number of
      cadavers pass through forensic departments around the world, and these cadavers
      could provide hundreds of research specimens, though they remain in the forensic
      unit for only a short time. The injection of a silicone mixture that quickly
      solidifies during autopsy would provide greater numbers of fresh specimens for
      study. The authors describe a technique for injecting a self-curing silicone
      mixture that can be used on autopsy specimens in a forensic unit. This technique
      does not interfere with routine autopsy findings. We describe the preparation of
      the mixture and autopsy specimens, the injection process, and the method for
      removing injected brains from cadavers. The solidifying process took a 1-h
      duration in this injection method and was in accord with autopsy procedure. The
      arterial bed was satisfactorily filled, and even small perforating branches and
      pial anastomoses were well demonstrated. Injecting autopsy specimens with the
      quick-solidifying silicone mixture allows anatomical studies of specimens even
      from cadavers admitted to forensic departments for only a short time. This method
      can provide neurosurgery laboratories with sufficient numbers of specimens
      appropriate for various studies.

PMID- 16906437
TI  - Genotype-by-sex interaction in the aetiology of type 2 diabetes mellitus: support
      for sex-specific quantitative trait loci in Hypertension Genetic Epidemiology
      Network participants.
AB  - AIMS/HYPOTHESIS: While there are sex-related differences in both the prevalence
      of type 2 diabetes mellitus and disease risk factors, there is only limited
      research on sex-specific influences on type 2 diabetes aetiology within the same
      study population. Thus, we assessed genotype-by-sex interaction using a liability
      threshold model in an attempt to localise sex-specific type 2 diabetes
      quantitative trait loci (QTLs). SUBJECTS, MATERIALS AND METHODS: Hypertensive
      siblings and their offspring and/or parents in the Hypertension Genetic
      Epidemiology Network of the Family Blood Pressure Program were recruited from
      five field centres. The diabetic phenotype was adjusted for race, study centre,
      age and non-linear age effects. In total, 567 diabetic individuals were
      identified in 385 families. Variance component linkage analyses in the combined
      sample and stratified by sex and race were performed (SOLAR program) using race
      specific marker allele frequencies derived from a random sample of participants
      at each centre. RESULTS: We observed a QTL-specific genotype-by-sex interaction
      (p=0.009) on chromosome 17 at 31 cM, with females displaying a robust adjusted
      logarithm of odds (LOD) of 3.0 compared with 0.2 in males and 1.3 in the combined
      sample. Three additional regions demonstrating suggestive evidence for linkage
      were detected: chromosomes 2 and 5 in the female sample and chromosome 22
      (adjusted LOD=1.9) in the combined sample. CONCLUSIONS/INTERPRETATION: These
      findings suggest that multiple genes may regulate susceptibility to type 2
      diabetes, demonstrating the importance of considering the interaction of genes
      and environment in the aetiology of common complex traits.

PMID- 16906439
TI  - Prevalence of psychiatric disorders three years after the 1999 earthquake in
      Turkey: Marmara Earthquake Survey (MES).
AB  - BACKGROUND: The objective of the study is to describe the community prevalence of
      psychiatric disorder, mainly posttraumatic stress disorder (PTSD) and Major
      Depressive Disorder (MDD) 3 years after a devastating earthquake. METHODS: Three
      years after the Marmara Earthquake, 683 individuals from the epicentre were
      randomly selected to form a representative sample and were assessed with
      Composite International Diagnostic Interview (CIDI), General Health Questionnaire
      (GHQ), Traumatic Stress Symptom Checklist (TSSC) and Beck Depression Inventory
      (BDI). RESULTS: The 36 months prevalence of PTSD and MDD after the Marmara
      Earthquake were 19.2% and 18.7% respectively. The current prevalence of PTSD and
      MDD in the affected community was found to be 11.7% and 10.5%, respectively. PTSD
      and MDD were the most prevalent disorders after the disaster and showed a
      decrease over time. However, only 38.9% of the PTSD cases identified at any time
      over the 3 years were in remission at the 3rd-year. The co-occurrence of MDD with
      PTSD resulted in a decrease in the rate of recovery from PTSD. MDD was also the
      most prevalent disorder accompanying PTSD. Of all the subjects 37.5% with PTSD
      still met the MDD criteria at the 3rd year postearthquake. CONCLUSIONS: In
      comparison with the data from pre-earthquake national mental health profile, the
      present study showed that the prevalence of MDD, panic disorder, OCD, GAD, social
      phobia and special phobias were still higher in the affected region 3 years after
      the earthquake.

PMID- 16906440
TI  - Phytohormones and rice crop yield: strategies and opportunities for genetic
      improvement.
AB  - To feed an estimated world population of 8.9 billion by 2050, strategies for
      increasing grain production must be developed. Several agronomically important
      traits for increasing yield, such as plant height, grain number, and leaf
      erectness, have recently been characterized in rice (Oryza sativa L.). These
      traits are regulated primarily by three phytohormones: gibberellins, cytokinins,
      and brassinosteroids. The control of biosynthesis and degradation of these key
      phytohormones is discussed in terms of its importance for normal plant growth.
      Genes involved in the biosynthesis and regulation of these phytohormones can be
      used to develop effective strategies to increase grain yield. Genetic
      manipulation of phytohormone-related gene expression is thus a practical strategy
      to generate high-yielding transgenic plants through the modification of levels
      and profile of endogenous phytohormones.

PMID- 16906441
TI  - Cloned transgenic heart-healthy pork?
AB  - Here I comment on the production and uses of swine that express a humanized fat-1
      gene. The gene product is a fatty acid desaturase that converts omega-6 fatty
      acids to omega-3 fatty acids. Omega-3 fatty acids have been implicated as being
      important for reproductive success, maintaining a healthy cardiovascular system,
      sustaining a functional immune system, and even preventing depression and cancer.
      The descendants of these hfat-1 transgenic swine will be very useful as models of
      the human condition, and if they are permitted to enter the food chain, they may
      improve human health.

PMID- 16906443
TI  - Chromosomal localization of a proinsulin transgene in Japanese quail by laser
      pressure catapulting.
AB  - Transgenic avian bioreactors produce therapeutic recombinant proteins in egg
      white. To date, however, methods for transgenic modification of the avian genome
      or determining transgenic status of individual birds are scarce. The dual, but
      interrelated, goals of this research were to: (1) develop a method of detecting
      stable DNA insertion into Japanese quail; and (2) provide a method for gene
      location on avian chromosomes. We created Teflon-coated coverslip slides to
      facilitate laser pressure catapulting of avian chromosomes for DNA amplification
      and nucleotide sequencing. Transgenic G2 Japanese quail, containing germline
      incorporation of proinsulin, were identified by isolation of chromosomes using
      laser microdissection and laser pressure catapulting. Subsequent amplification of
      each chromosome identified 2-5 chromosomes with the proinsulin transgene
      inserted. Nucleotide sequencing of each chromosomal insertion was identical to
      the proinsulin portion of the original vector. By applying laser pressure
      catapulting and PCR of individual chromosomes, we were able to determine that the
      transgene correctly inserted into avian chromosomes and that the majority of the
      insertions occurred within microchromosomes. Because many potential therapeutic
      transgenes have similar or nearly identical nucleotide sequence to the host's
      native gene, laser microdissection and subsequent analysis may be required for
      detailed documentation of transgene expression before proceeding with transgenic
      protein production.

PMID- 16906442
TI  - Assessing the potential for unintended effects in genetically modified potatoes
      perturbed in metabolic and developmental processes. Targeted analysis of key
      nutrients and anti-nutrients.
AB  - Targeted compositional analysis was carried out on transgenic potato tubers of
      either cultivar (cv.) Record or cv. Desiree to assess the potential for
      unintended effects caused by the genetic modification process. The range of
      transgenic lines analysed included those modified in primary carbohydrate
      metabolism, polyamine biosynthesis and glycoprotein processing. Controls included
      wildtype tubers, tubers produced from plants regenerated through tissue culture
      (including a callus phase) and tubers derived from transformation with the 'empty
      vector' i.e. no specific target gene included (with the exception of the
      kanamycin resistance gene as a selectable marker). Metabolite analysis included
      soluble carbohydrates, glycoalkaloids, vitamin C, total nitrogen and fatty acids.
      Trypsin inhibitor activity was also assayed. These cover the major compounds
      recommended by the OECD in their Consensus Document on Compositional
      Considerations for New Varieties of Potatoes: Key Food and Feed Nutrients, Anti
      Nutrients and Toxicants (2002). Data was statistically analysed using analysis of
      variance (ANOVA) for individual compounds and, where applicable, principal
      component analysis (PCA). In general, targeted compositional analysis revealed no
      consistent differences between GM lines and respective controls. No construct
      specifically induced unintended effects. Statistically significant differences
      between wildtype controls and specific GM lines did occur but appeared to be
      random and not associated with any specific construct. Indeed such significant
      differences were also found between wildtypes and both tissue culture derived
      tubers and tubers derived from transformation with the empty vector. This raises
      the possibility that somaclonal variation (known to occur significantly in
      potato, depending on genotype) may be responsible for an unknown proportion of
      any differences observed between specific GM lines and the wildtype. The most
      obvious differences seen in GC-MS profiles were between the two potato varieties
      used in the study.

PMID- 16906444
TI  - Expression of the lipid transfer protein Ace-AMP1 in transgenic wheat enhances
      antifungal activity and defense responses.
AB  - To enhance fungal disease resistance, wheat plants (cv. Bobwhite) were engineered
      to constitutively express the potent antimicrobial protein Ace-AMP1 from Allium
      cepa, driven by a maize ubiquitin promoter along with its first intron. The bar
      gene was used for selection of putative transformants on medium containing
      phosphinothricin (PPT). Transgene inheritance, integration and stability of
      expression were confirmed over two generations by PCR, Southern, northern and
      western blot analyses, respectively. The levels of Ace-AMP1 in different
      transgenic lines correlated with the transcript levels of the transgene. Up to
      50% increase in resistance to Blumeria graminis f. sp. tritici was detected in
      detached leaf assays. In ears of transgenic wheat inoculated with Neovossia
      indica, Ace-AMP1 intensified expression of defense-related genes. Elevated levels
      of salicylic acid and of transcripts of phenylalanine ammonia lyase (PAL),
      glucanase (PR2) and chitinase (PR3) in the transgenic plants indicated
      manifestation of systemic acquired resistance (SAR).

PMID- 16906445
TI  - Evaluation of laser-assisted lentiviral transgenesis in bovine.
AB  - Lentiviral transduction of oocytes or early embryos is an efficient strategy to
      generate transgenic rodents and livestock. We evaluated laser-based microdrilling
      (MD) of the zona pellucida, which is a physical barrier for viral infection, and
      subsequent incubation in virus suspension as a new route for lentiviral
      transgenesis in bovine. Lentiviral vectors carrying an eGFP expression cassette
      were used to transduce oocytes or zygotes after MD as compared to the established
      subzonal virus injection technique (MI). The type of manipulation (MD vs. MI) did
      not affect cleavage rates, but had a significant effect on blastocyst rates (P <
      0.001). MI of virus or sham-MI (buffer) resulted in higher blastocyst rates as
      compared to MD, both in the oocyte and zygote treatment groups. The latter
      exhibited higher rates of early cleavage (P < 0.05) and blastocyst rates (P <
      0.01). The proportion of eGFP expressing blastocysts was higher after infection
      of oocytes (MD: 44 +/- 9%; MI: 67 +/- 8%) than after infection of zygotes (MD: 26
      +/- 8%; MI: 26 +/- 9%). Overall efficacy (eGFP-positive blastocysts per treated
      oocytes or zygotes) was highest after MI of oocytes (18 +/- 2%). Our study
      demonstrates the feasibility of laser-assisted lentiviral gene transfer into
      bovine oocytes and zygotes. However, further optimization of the procedure is
      required, mainly to reduce the incidence of polyspermy after MD of oocytes and to
      eliminate negative effects of MD on early embryonic development.

PMID- 16906446
TI  - Expression of the Newcastle disease virus fusion protein in transgenic maize and
      immunological studies.
AB  - Transgenic plants have been employed successfully as a low-cost system for the
      production of therapeutically valuable proteins, including antibodies, antigens
      and hormones. Here, we report the expression of the fusion (F) gene of the
      Newcastle disease virus (NDV) in transgenic maize plants. The expression of the
      transgene, driven by the maize ubiquitin promoter, caused accumulation of the F
      protein in maize kernels. The presence of the transgene was verified by Southern
      and western blots. Feeding chickens with kernels containing the F protein induced
      the production of antibodies, which conferred protection against a viral
      challenge. This protection was comparable to that conferred by a commercial
      vaccine. Possible uses of this plant-based F protein as a potential mucosal
      vaccine are discussed.

PMID- 16906447
TI  - Characterization and multi-generational stability of the growth hormone transgene
      (EO-1alpha) responsible for enhanced growth rates in Atlantic Salmon.
AB  - Transgenic technologies provide a promising means by which desirable traits can
      be introduced into cultured fish species within a single generation thus
      accelerating the production of genetically superior broodstock for aquaculture.
      However, before such fish are allowed to be marketed as food they must receive
      government regulatory approval. Two pivotal regulatory requirements are: (1)
      complete characterization of the genomically integrated transgene and, (2)
      demonstration that the transgene remains stable over multiple generations. We
      have generated a stable line of growth hormone (GH) transgenic Atlantic salmon
      (Salmo salar) using an "all fish" gene construct (opAFP-GHc2) containing a growth
      hormone cDNA from chinook salmon whose expression is regulated by the 5' promoter
      and 3' termination regions derived from an ocean pout antifreeze protein (AFP)
      gene. In this study we show that a reorganized form of the opAFP-GHc2 construct
      (termed EO-1alpha) integrated as a single functional copy into a 35 bp repeat
      region of the genomic DNA. PCR based mapping revealed that the linear sequence of
      the EO-1alpha integrant was organized as follows: base pairs 1580-2193 of the
      ocean pout promoter region followed by the intact chinook salmon GH cDNA, the
      complete ocean pout antifreeze 3' region, and the first 1678 bp of the ocean pout
      antifreeze 5' region. Sequence analysis of the EO-1alpha integrant and genomic
      flanking regions in F2 and F4 generation salmon revealed that they were
      identical. In addition, apart from the disruption at the integration sites, the
      consensus sequences of the integrant in these two generations of salmon were
      identical to the sequence of the opAFP-GHc2 construct. These results indicate
      that the EO-1alpha transgene codes for the chinook salmon GH, and that the
      transgene and the integration site have remained stable over multiple
      generations.

PMID- 16906449
TI  - An inverted repeat transgene with a structure that cannot generate double
      stranded RNA, suffers silencing independent of DNA methylation.
AB  - Transgene silencing in plants is most often dependent on homologous sequences,
      e.g. tandemly repeated T-DNAs. We have identified an Arabidopsis line (ex2-4 line
      4) displaying silencing of the T-DNA-born nptII gene. This line contains a
      truncated copy of the T-DNA encompassing the nptII gene with its nos promoter
      adjacent to an intact T-DNA copy. The orientation of the intact and the truncated
      copies preclude the generation of a double-stranded nptII transcript. Therefore,
      we have investigated the genomic landscape surrounding T-DNA insertion in the
      silenced ex2-4 line 4 and five single-copy ex2-4 lines without silencing in
      search of features that might explain the silencing phenomenon. GC content,
      putative matrix-attachment regions and transcriptional interference from
      neighbouring genes could all be ruled out as major causes of silencing.
      Bisulphite sequencing revealed de novo methylation of the nos promoter both in
      non-silenced and silenced plants of this line, thus silencing was not correlated
      to DNA methylation level. Also, the methylation pattern deviated from that
      characteristic for RNA-mediated DNA methylation and silencing. Our data therefore
      suggest that ex2-4 line 4 represents a case where silencing is due to DNA-DNA
      pairing, i.e. pairing between the intact T-DNA and the adjacent truncated,
      inverted T-DNA copy.

PMID- 16906448
TI  - Expression of the cry9Aa2 B.t. gene in tobacco chloroplasts confers resistance to
      potato tuber moth.
AB  - We report here the control of potato tuber moth (Phthorimaea operculella) by
      incorporating a truncated Bacillus thuringiensis cry9Aa2 gene in the plastid
      genome. Plasmids pSKC84 and pSKC85 are derivatives of a new polycistronic plastid
      transformation vector, pPRV312L, that carries spectinomycin resistance (aadA) as
      a selective marker and targets insertions in the trnI-trnA intergenic region. The
      Cry9Aa2 N-terminal region (82.1 kDa; 734 amino acids) was expressed in a
      cassette, which consists of 49 nucleotides of the cry9Aa2 leader and the 3'
      untranslated region of the plastid rbcL gene (TrbcL), and relies on readthrough
      transcription from the plastid rRNA operon. In a tobacco leaf bioassay,
      expression of Cry9Aa2 conferred resistance to potato tuber moth. In accordance,
      the Cry9Aa2 insecticidal protein accumulated to high levels, approximately 10% of
      the total soluble cellular protein and approximately 20% in the membrane
      fraction. However, high-level Cry9Aa2 expression significantly delayed plant
      development. Thus, a practical system to control potato tuber moth by Cry9Aa2
      expression calls for down-regulation of its expression.

PMID- 16906450
TI  - Prey-mediated effects of transgenic canola on a beneficial, non-target, carabid
      beetle.
AB  - Transgenic plants producing insecticidal proteins from Bacillus thuringiensis
      (Bt) can control some major insect pests and reduce reliance on sprayed
      insecticides. However, large scale adoption of this technology has raised
      concerns about potential negative effects, including evolution of pest resistance
      to Bt toxins, transgene flow from Bt crops to other plants, and harm to non
      target beneficial organisms. Furthermore, concern has also been expressed over
      the effects this technology may have on biodiversity in general. Ecologically
      relevant risk assessment is therefore required (Risk = Hazard x Exposure).
      Transgenic plants that produce Bt toxins to kill insect pests could harm
      beneficial predators. This might occur directly by transmission of toxin via
      prey, or indirectly by toxin-induced reduction in prey quality (Hazard). To test
      these hypotheses, we determined the effects of Bt-producing canola on a predatory
      ground beetle (Pterostichus madidus) fed larvae of diamondback moth (Plutella
      xylostella) that were either susceptible or resistant to the Bt toxin. Survival,
      weight gain, and adult reproductive fitness did not differ between beetles fed
      prey reared on Bt-producing plants and those fed prey from control plants.
      Furthermore, while Bt-resistant prey was shown to deliver high levels of toxin to
      the beetle when they were consumed, no significant impact upon the beetle was
      observed. Subsequent investigation showed that in choice tests (Exposure),
      starved and partially satiated female beetles avoided Bt-fed susceptible prey,
      but not Bt-fed resistant prey. However, in the rare cases when starved females
      initially selected Bt-fed susceptible prey, they rapidly rejected them after
      beginning to feed. This prey type was shown to provide sufficient nutrition to
      support reproduction in the bioassay suggesting that Bt-fed susceptible prey is
      acceptable in the absence of alternative prey, however adults possess a
      discrimination ability based on prey quality. These results suggest that the
      direct effects of Bt-producing canola on predator life history was minimal, and
      that predators' behavioural preferences may mitigate negative indirect effects of
      reduced quality of prey caused by consumption of Bt-producing plants. The results
      presented here therefore suggest that cultivation of Bt canola may lead to
      conservation of non-target predatory and scavenging organisms beneficial in pest
      control, such as carabids, and may therefore provide more sustainable
      agricultural systems than current practices. In addition, minimal impacts on
      beneficial carabids in agro-ecosystems suggest that Bt canola crops are likely to
      be compatible with integrated pest management (IPM) systems.

PMID- 16906451
TI  - Consumption of milk from transgenic goats expressing human lysozyme in the
      mammary gland results in the modulation of intestinal microflora.
AB  - Lysozyme is a key antimicrobial component of human milk that has several health
      promoting functions including the development of a healthy intestinal tract.
      However, levels of lysozyme in the milk of dairy animals are negligible. We have
      generated transgenic dairy goats that express human lysozyme (HLZ) in their milk
      in an attempt to deliver the benefits of human milk in a continual fashion. To
      test the feasibility of this transgenic approach to achieve a biological impact
      at the level of the intestine, feeding trials were conducted in two animal
      models. Pasteurized milk from HLZ transgenic animals was fed to both kid goats
      (ruminant model) and young pigs (human model), and the numbers of total coliforms
      and Escherichia coli present in the small intestine were determined. Data from
      this proof-of-principle study demonstrate that milk from transgenic animals was
      capable of modulating the bacterial population of the gut in both animal models.
      Pigs that consumed pasteurized milk from HLZ transgenic goats had fewer numbers
      of coliforms and E. coli in their intestine than did those receiving milk from
      non-transgenic control animals. The opposite effect was seen in goats. Milk from
      these transgenic animals not only represent one of the first transgenic food
      products with the potential of benefiting human health, but are also a unique
      model to study the development and role of intestinal microflora on health, well
      being and resistance to disease.

PMID- 16906452
TI  - Heterogeneity of breast cancer among patients and implications for patient
      selection for adjuvant chemotherapy.
AB  - Although the benefits of adjuvant chemotherapy are not controversial, the
      absolute effect of such therapy is small. Therefore, there is a need to identify
      biomarkers that can help select patients with localized breast cancer for
      treatment. Despite intense research in this field, no biomarker has been shown to
      be useful to predict benefit of adjuvant chemotherapy in daily practice. This can
      partially be explained by the fact that breast cancer is composed of several
      distinct subclasses, as shown by large-scale genomic analyses. In this review, we
      discuss why the current research approach based on a single biomarker is limited
      by the heterogeneity of cancer among patients. We then propose three solutions to
      improve the research strategies in this field: investigate one biomarker in a
      single homogeneous subclass to improve its predictive value; study the predictive
      value of multibiomarker assays in larger populations; and use functional pathways
      to predict the efficacy of a given drug.

PMID- 16906453
TI  - Calculation of the penetration depth of X-rays in intact pharmaceutical film
      coated tablets by microdiffractometry.
AB  - PURPOSE: (i) Develop a method to calculate the penetration depth of X-rays in
      intact film-coated tablets, and validate it using model bilayer tablets. (ii)
      Characterize the physical form of drug in intact pharmaceutical film-coated
      tablets by XRD. MATERIALS AND METHODS: An equation for the calculation of the
      penetration depth of X-rays, as a function of the incident angle, was derived.
      Model bilayer tablets were prepared to validate the calculation method. The upper
      layer of the tablets consisted only of microcrystalline cellulose, while the
      lower layer was a mixture of cerium oxide (10% w/w), blue dye (5% w/w) and
      microcrystalline cellulose. The total tablet thickness was 3,500 microm, with the
      upper layer thickness ranging from 200 to 700 microm. The diffracted intensity of
      a cerium oxide peak in the lower layer was determined using a microdiffractometer
      system (CuKalpha radiation) with a two-dimensional area detector. The calculated
      penetration depth of X-rays was compared with that determined by XRD. After
      validation of the XRD method, commercial ibuprofen tablets were characterized.
      RESULTS: The penetration depth calculated by the method developed in this study
      was, in general, in good agreement with that determined experimentally by XRD. In
      commercial ibuprofen tablets, the coating material exhibited peaks due to TiO2
      (25.4 degrees 2 theta) and Fe2O3 (33.3 degrees). However, these did not interfere
      with the characteristic peak of ibuprofen (22.2 degrees). CONCLUSION: We
      developed a method for calculation of penetration depth of X-rays in film-coated
      tablets and validated it using the model bilayer tablets. This method enables the
      characterization of the active pharmaceutical ingredient in different regions (at
      different depths) of the film-coated tablet. Since the technique is
      nondestructive, the same tablet can be repeatedly analyzed during stability
      studies.

PMID- 16906454
TI  - Metrics for external model evaluation with an application to the population
      pharmacokinetics of gliclazide.
AB  - PURPOSE: The aim of this study is to define and illustrate metrics for the
      external evaluation of a population model. MATERIALS AND METHODS: In this paper,
      several types of metrics are defined: based on observations (standardized
      prediction error with or without simulation and normalized prediction
      distribution error); based on hyperparameters (with or without simulation); based
      on the likelihood of the model. All the metrics described above are applied to
      evaluate a model built from two phase II studies of gliclazide. A real phase I
      dataset and two datasets simulated with the real dataset design are used as
      external validation datasets to show and compare how metrics are able to detect
      and explain potential adequacies or inadequacies of the model. RESULTS:
      Normalized prediction errors calculated without any approximation, and metrics
      based on hyperparameters or on objective function have good theoretical
      properties to be used for external model evaluation and showed satisfactory
      behaviour in the simulation study. CONCLUSIONS: For external model evaluation,
      prediction distribution errors are recommended when the aim is to use the model
      to simulate data. Metrics through hyperparameters should be preferred when the
      aim is to compare two populations and metrics based on the objective function are
      useful during the model building process.

PMID- 16906455
TI  - Co-expression of vascular endothelial growth factor and interleukin-1 receptor
      antagonist improves human islet survival and function.
AB  - PURPOSE: Ex vivo gene therapy approaches can improve the outcome of islet
      transplantation for treating type I diabetes. We have previously shown the
      improvement in islet function and vascularization following ex vivo transfection
      for human vascular endothelial growth factor (hVEGF) gene expression. In this
      study, we tested the hypothesis that co-expression of two genes, which target
      different challenges faced by islets post-transplantation, supplement each other
      to improve the survival and function of islets. We determined whether there is an
      additive effect of hVEGF and human interleukin-1 receptor antagonist (hIL-1Ra)
      gene expression in human islets. MATERIALS AND METHODS: Human islets were co
      infected with adenoviral vectors encoding hVEGF and hIL-1Ra. Islets were then
      incubated with a cocktail of inflammatory cytokines (IL-1beta+TNFalpha+IFNgamma),
      and islet viability and function were determined. In vivo function was evaluated
      by transplanting islets under the kidney capsules of streptozotocin-induced non
      obese diabetic severe combined immunodeficient (NOD-SCID) mice. RESULTS:
      Infection of human islets with Adv-hVEGF and/or Adv-hIL-1Ra inhibited expression
      of inducible nitric oxide synthase (iNOS), decreased the production of nitric
      oxide (NO), and prevented the loss of in vitro glucose-stimulated insulin
      response and viability. Moreover, co-expression of hVEGF and hIL-1Ra reduced the
      blood glucose level of mice, and increased the level of blood insulin and c
      peptide upon glucose challenge. CONCLUSIONS: Our results indicated that co
      expression of genes that target different insults to transplanted islets can
      improve the outcome of islet transplantation better than either gene alone.

PMID- 16906456
TI  - Application of clinical trial simulation to compare proof-of-concept study
      designs for drugs with a slow onset of effect; an example in Alzheimer's disease.
AB  - OBJECTIVE: Clinical trial simulation (CTS) was used to select a robust design to
      test the hypothesis that a new treatment was effective for Alzheimer's disease
      (AD). Typically, a parallel group, placebo controlled, 12-week trial in 200-400
      AD patients would be used to establish drug effect relative to placebo (i.e., Ho:
      Drug Effect = 0). We evaluated if a crossover design would allow smaller and
      shorter duration trials. MATERIALS AND METHODS: A family of plausible drug and
      disease models describing the time course of the AD assessment scale (ADAS-Cog)
      was developed based on Phase I data and literature reports of other treatments
      for AD. The models included pharmacokinetic, pharmacodynamic, disease
      progression, and placebo components. Eight alternative trial designs were
      explored via simulation. One hundred replicates of each combination of drug and
      disease model and trial design were simulated. A 'positive trial' reflecting drug
      activity was declared considering both a dose trend test (p < 0.05) and pair-wise
      comparisons to placebo (p < 0.025). RESULTS: A 4 x 4 Latin Square design was
      predicted to have at least 80% power to detect activity across a range of drug
      and disease models. The trial design was subsequently implemented and the trial
      was completed. Based on the results of the actual trial, a conclusive decision
      about further development was taken. The crossover design provided enhanced power
      over a parallel group design due to the lower residual variability. CONCLUSION:
      CTS aided the decision to use a more efficient proof of concept trial design,
      leading to savings of up to US 4 M dollars in direct costs and a firm decision 8
      12 months earlier than a 12-week parallel group trial.

PMID- 16906457
TI  - Near-infrared imaging for studying homogeneity of protein-sugar mixtures.
AB  - PURPOSE: To investigate the applicability of near-infrared (NIR) imaging for
      assessing the homogeneity of dried protein-sugar formulations. METHODS: Physical
      mixtures of lysozyme and trehalose in different ratios were prepared and analyzed
      by near-infrared (NIR) imaging with a spatial resolution of 10 or 40 microm. To
      define and select the best imaging strategy, besides visual inspection of the
      images, several approaches for data processing were tested: single wavelength
      intensity, peak/height ratio of two specific wavelengths, correlation coefficient
      with a reference spectrum and principal component analysis (PCA). In order to
      relate the contrast directly to concentration differences of lysozyme and
      trehalose, quantitative models were created based on correlation coefficient and
      partial least squares (PLS) regression. The selected imaging method was applied
      to compare the homogeneity of a supercritical fluid (SCF) dried and a freeze
      dried lysozyme-trehalose mixture. RESULTS: All tested methods confirmed each
      other and showed spatial heterogeneity in the lysozyme and trehalose contents of
      the physical mixtures. However, multivariate data processing methods (correlation
      coefficient and PCA/PLS) resulted in more distinct contrasts than univariate
      approaches (single wavelength analysis) and allowed a quantitative estimation of
      the homogeneity. As shown by NIR imaging in combination with the correlation
      coefficient or the PLS method, the SCF dried lysozyme-trehalose formulation was
      at least as homogeneous as its lyophilized counterpart, at 10 microm pixel size
      resolution. CONCLUSIONS: NIR imaging is a useful tool for studying the
      homogeneity of dried protein-sugar formulations.

PMID- 16906458
TI  - Micronization of insulin by high pressure homogenization.
AB  - PURPOSE: The aim of this study was to establish the high pressure homogenization
      of proteins in non-aqueous suspension as an alternative method for classical
      micronization strategies and to investigate the effect of high pressure on
      protein stability and bioactivity. METHODS: The influence of drug loading,
      homogenization pressure and cycles on particle size reduction was investigated by
      experimental design using a Box Behnken matrix with insulin as a model compound.
      Particle size measurements were performed by laser light scattering. Protein
      stability was investigated by HPLC and HPLC-MS analysis and the bioactivity of
      insulin was tested in a chondrocyte proliferation assay. For investigations into
      the effect of temperature on protein stability, insulin was micronized in molten
      lipid at 75 degrees C in one cycle at 1,000 bar. RESULTS: Within one
      homogenization cycle at 1,500 bar, the particle size of insulin could be reduced
      from 15.8 to 7.3 microm, six cycles resulted in a particle size of 3.7 microm
      d(0.5) (50% of the particles are smaller than the indicated value). Evaluation of
      the response surface diagram revealed that the homogenization pressure had the
      highest impact on micronization efficiency, followed by the number of
      homogenization cycles. Protein stability was maintained during the micronization
      process as well as bioactivity. Micronization at elevated temperature (75 degrees
      C) had no effect on protein stability. CONCLUSION: High pressure homogenization
      of protein suspensions can be used as an alternative method for the micronization
      of proteins without affecting protein stability or bioactivity.

PMID- 16906459
TI  - C677T methylentetrahydrofulate reductase and angiotensin converting enzyme gene
      polymorphisms in patients with Alzheimer's disease in Iranian population.
AB  - In recent years numerous data suggest that vascular risk factors may be play a
      role in Alzheimer's disease (AD). To determine the association of AD with
      methylentetrahydrofulate reductase (MTHFR) and angiotensin converting enzyme
      (ACE) as two main vascular risk factors, we examined MTHFR C677T and ACE
      insertion/deletion (I/D) gene polymorphism in 117 late-onset AD cases and 125
      controls. We found no difference in ACE I/D genotype distribution between AD
      cases and control (P > 0.05) but there was a significant association between AD
      and the common MTHFR polymorphism C677T. The T allele conferred an increased risk
      of AD compared to carrying a C allele (P = 0.001, OR = 1.97, 95% CI: 1.3-2.09).
      Our result suggests a significant increase in risk of AD in cases with the MTHFR
      T allele, atleast in the Iranian population.

PMID- 16906460
TI  - Orientation and affective expression effects on face recognition in Williams
      syndrome and autism.
AB  - We sought to clarify the nature of the face processing strength commonly observed
      in individuals with Williams syndrome (WS) by comparing the face recognition
      ability of persons with WS to that of persons with autism and to healthy controls
      under three conditions: Upright faces with neutral expressions, upright faces
      with varying affective expressions, and inverted faces with neutral expressions.
      No differences were observed under the upright/neutral expression condition.
      However, the WS group was more accurate than the autism group when discriminating
      upright faces with varying affective expressions, whereas the opposite pattern
      emerged when discriminating inverted faces. We interpret these differences as a
      reflection of the contrasting social features of the two syndromes.

PMID- 16906461
TI  - Brief report: application of the TEACCH program on Chinese pre-school children
      with autism--Does culture make a difference?
AB  - A longitudinal study was conducted on 34 children with autism to evaluate the
      usefulness of the Treatment and Education of Autistic and related Communication
      Handicapped Children (TEACCH) program for Chinese pre-school children in Hong
      Kong. Eighteen children received full-time center-based TEACCH program training.
      The control group included 16 children who received different types of
      individualized or group training but not TEACCH program training. Instruments
      validated in Hong Kong were used to assess the children's cognitive, social
      adaptive functioning and developmental abilities before and during the training
      at 6-month intervals for 12 months. Children in the experimental group showed
      better outcomes at posttest. They also showed progress in different developmental
      domains over time. The study provided initial support for the effectiveness of
      using the TEACCH program with Chinese children.

PMID- 16906462
TI  - Who cares? Revisiting empathy in Asperger syndrome.
AB  - A deficit in empathy has consistently been cited as a central characteristic of
      Asperger syndrome (AS), but previous research on adults has predominantly focused
      on cognitive empathy, effectively ignoring the role of affective empathy. We
      administered the Interpersonal Reactivity Index (IRI), a multi-dimensional
      measure of empathy, and the Strange Stories test to 21 adults with AS and 21
      matched controls. Our data show that while the AS group scored lower on the
      measures of cognitive empathy and theory of mind, they were no different from
      controls on one affective empathy scale of the IRI (empathic concern), and scored
      higher than controls on the other (personal distress). Therefore, we propose that
      the issue of empathy in AS should be revisited.

PMID- 16906464
TI  - The challenge of treating forensic dual diagnosis clients: comment on "integrated
      treatment for jail recidivists with co-occurring psychiatric and substance use
      disorders".

PMID- 16906463
TI  - What facilitates social engagement in preschool children with autism?
AB  - We studied the association between an adult's behavior and episodes of social
      engagement (ESEs) in young children with autism during play-based assessment.
      ESEs were defined as events in which a child looked toward the adult's face and
      simultaneously showed an additional form of communicative behavior. The adult's
      behavior before each ESE, and before time-sampled control periods, was rated
      using Coding Active Sociability in Preschoolers with Autism (CASPA). As
      predicted, adult musical/motoric activity, communications that followed the
      child's focus of attention, scaffolding through social routines, imitations of
      the child, and adult repetitions were significantly more prevalent before ESEs,
      but cognitive assessment activities, adult inactivity, and "ignoring" were
      significantly less prevalent. We consider the implications for understanding the
      developmental psychopathology of autism.

PMID- 16906465
TI  - Examining the effects of a national alcohol-free fraternity housing policy.
AB  - This investigation examined the effectiveness of an alcohol-free fraternity
      housing policy on the risky alcohol use of members of a national fraternity
      (N=718). Comparisons of members in chapters with fraternity housing (FH) and
      those in chapters without housing (NFH) over time revealed no policy-related
      effects on measures of alcohol use. Among FH members, comparisons of those who
      lived in fraternity housing and those who lived in other housing also found no
      effects. FH members reported that the policy was implemented moderately well;
      however, it may have shifted alcohol use from fraternity housing to other
      settings.

PMID- 16906466
TI  - Genetic and environmental factors affecting self-rated health from age 16-25: a
      longitudinal study of Finnish twins.
AB  - We analyzed genetic and environmental determinants of self-rated health and its
      change from adolescence to early adulthood. Questionnaires were mailed to Finnish
      twins born 1975-1979 at ages 16, 17, 18 1/2 and, on average, 25 years of age
      (N=2465 complete twin pairs). The data were analyzed using quantitative genetic
      methods for twin data by the Mx statistical package. Heritability of self-rated
      health was greatest at age 16 (63%, 95% confidence intervals (CI) 56-67%, men and
      women together) and declined steadily to age 25 (33%, 95% CI 25-41%). The
      residual variation was due to unshared environments. Health ratings at different
      ages were modestly correlated (r=0.33-0.61). These correlations were mainly due
      to genetic factors, but unshared environment also contributed to them. An
      important challenge for further research is to identify environmental influences
      contributing to self-rated health independently of, or in interaction with,
      genetic factors.

PMID- 16906467
TI  - The influence of stress and energy level on learning muscle relaxation during
      gross-motor task performance using electromyographic feedback.
AB  - The aim was to investigate the influence of mood on learning muscle relaxation.
      Self-reported mood (assessed by the Stress-Energy Checklist) at baseline was
      related to learning muscle relaxation induced by electromyographic feedback
      training during performance of a gross-motor task. Feedback training was provided
      either intermittently (Intermittent Feedback Task, IF, n=12) or continuously
      (Continuous Feedback Task, CF, n=9). Results reveal a negative correlation
      between the learning effect at short-term and energy dimension for the IF Task.
      It can be concluded that mood experienced prior to a learning task is relevant
      for the learning effect and this effect may be dependent on the schedule of
      feedback used.

PMID- 16906468
TI  - Transfer of heart rate feedback training to reduce heart rate response to
      laboratory tasks.
AB  - To examine whether transfer of heart rate (HR) feedback training to tasks not
      used during training could be improved by using multiple tasks during training, a
      modified multiple baseline across tasks, single subject design study was
      conducted using six high HR-reactive young adults. Participants received HR
      feedback training during the presentation of a videogame, and transfer of
      training was assessed to a mental arithmetic challenge and handgrip task.
      Transfer of training was next assessed following training with the mental
      arithmetic challenge and handgrip task. HR responses to each training task with
      no HR feedback were assessed during a pre-treatment session, an immediate post
      training period following training on each task, a short delay (1-2 days) post
      training session, and a long delay (1-2 weeks) post-training session. HR response
      to a novel speech task was assessed at pre-treatment and during short delay and
      long delay post-training sessions. Results revealed that participants reduced HR
      during training and generally maintained this reduction in HR during the
      immediate post-training assessment when HR feedback was not present. Participants
      were not able to reduce HR responses to tasks during short delay and long delay
      post-training sessions, and they were unable to transfer HR reduction skills to
      the speech task. Transfer of HR feedback training to new tasks was limited in
      nature and efforts to train across multiple stressors did not appear to improve
      transfer of training.

PMID- 16906469
TI  - The impact on juror verdicts of judicial instruction to disregard inadmissible
      evidence: a meta-analysis.
AB  - The effect on juror verdicts of judicial instructions to disregard inadmissible
      evidence was evaluated using meta-analysis. One hundred seventy-five hypothesis
      tests from 48 studies with a combined 8,474 participants were examined. Results
      revealed that inadmissible evidence (IE) has a reliable effect on verdicts
      consistent with the content of the IE. Judicial instruction to ignore the
      inadmissible evidence does not effectively eliminate IE impact. However, if
      judges provide a rationale for a ruling of inadmissibility, juror compliance may
      be increased. Contested evidence ruled admissible accentuates that information,
      resulting in a significant impact on verdicts. Suggestions for how the courts may
      mitigate the impact of inadmissible evidence more effectively are discussed.

PMID- 16906470
TI  - Barth syndrome presenting with acute metabolic decompensation in the neonatal
      period.
AB  - We describe two patients affected by Barth syndrome. Their symptoms became
      manifest on respectively the third and first day of their lives. Clinical
      presentation included poor sucking, lethargy, hypotonia, hypothermia and
      cardiomyopathy. Laboratory findings such as hypoglycaemia, metabolic acidosis,
      elevated transaminases, hyperlactacidaemia and mild hyperammonaemia pointed to an
      inborn error of energy metabolism with possible mitochondrial involvement.
      Molecular analysis of the TAZ (G4.5) gene showed the c.877G > A mutation leading
      to the G197R amino acid substitution in patient 1, and the new splice donor c.829
      + 1G > A genetic lesion in patient 2.

PMID- 16906471
TI  - Bilateral nuclear cataracts as the first neonatal sign of Fanconi-Bickel
      syndrome.
AB  - A patient with early bilateral nuclear cataracts and subsequent diagnosis of
      Fanconi-Bickel syndrome is described. Despite impaired galactose and glucose
      metabolism, cataracts have been reported in only few cases with this disorder. We
      conclude that Fanconi-Bickel syndrome should be considered in the differential
      diagnosis of neonatal cataracts. The pathogenesis of this complication has not
      been fully elucidated.

PMID- 16906472
TI  - Haematological findings in children with inborn errors of metabolism.
AB  - Early detection and therapy of haematological abnormalities and/or diseases may
      improve the prognosis of metabolic disorders. Accordingly, we aimed to evaluate
      the frequency and types of haematological abnormalities in children[-31pc] with
      various inherited metabolic disorders. The study group comprised 46 children with
      metabolic disorders who were followed at the Pediatric Metabolism Unit and were
      referred to the Pediatric Hematology Unit for evaluation of anaemia between June
      2000 and 2005. The mean age of the children was 55.2 +/- 64.8 months at
      haematological evaluation (range 1 month-18 years, median 22.0 months); 16 were
      female and 30 were male. Of these 46 patients with anaemia, 25 of (54.3%) had
      anaemia of chronic disease (ACD), 9 (19.6%) had iron-deficiency anaemia (IDA), 7
      (15.2%) had megaloblastic anaemia due to vitamin B(12) deficiency, 3 (6.5%) had
      chronic haemolytic anaemia, 2 (4.3%) had autoimmune haemolytic anaemia, 1 had
      beta-thalassaemia major, and 1 had hereditary spherocytosis. In addition to the
      anaemia, bicytopenia or pancytopenia was found in 8 of 46 children (17.4%). The
      study indicated that in organic acidaemias including methylmalonic acidaemia,
      propionic acidaemia, isovaleric acidaemia, and argininosuccinic acidaemia, the
      majority of patients had ACD (75%), which was followed by vitamin B(12)
      deficiency anaemia and IDA (p < 0.001). In PKU, both nutritional anaemias and ACD
      were present at about same frequency: 46.7% and 40%, respectively (p > 0.05).
      This study suggested that congenital anaemias such as hereditary spherocytosis or
      thalassaemias should be kept in mind as a coexisting haematological diseases in
      young patients with inborn errors of metabolism. In conclusion, ACD and
      nutritional anaemias are the most prevalent anaemias seen in patients with inborn
      errors of metabolism. Early detection of the disease, early administration of
      specific diet, and close monitoring of the patients are very important factors to
      prevent the development of haematological diseases in patients with inborn errors
      of metabolism.

PMID- 16906473
TI  - Persistent increase of plasma butyryl/isobutyrylcarnitine concentrations as
      marker of SCAD defect and ethylmalonic encephalopathy.
AB  - High concentrations of butyryl/isobutyrylcarnitine (C(4)-carnitine) in plasma
      with increase of ethylmalonic acid (EMA) in urine point to different genetic
      entities, and further investigations are required to differentiate the possible
      underlying defect. Here we report three unrelated cases, two neurologically
      affected and one asymptomatic, with this abnormal metabolite pattern due either
      to mutations in the ETHE1 gene or to a short-chain acyl-CoA dehydrogenase (SCAD)
      defect.

PMID- 16906474
TI  - Structural and functional changes in peripheral vasculature of Fabry patients.
AB  - OBJECTIVE: Fabry disease is a lysosomal storage disorder due to deficient alpha
      galactosidase A activity, which leads to glycosphingolipid accumulation
      especially in vascular smooth-muscle and endothelial cells. Little is known about
      the effects of Fabry disease on peripheral artery function and structure.
      Therefore, we aimed to further characterize the peripheral vascular structural
      and functional changes in Fabry disease. METHODS AND RESULTS: We measured
      structural and functional vascular parameters, including intima-media thickness
      (IMT) of brachial and carotid arteries and abdominal aorta, carotid and aortic
      compliance, and brachial artery flow-mediated dilatation (FMD) in 17 Fabry
      patients and 34 healthy controls matched for age, sex and smoking. Carotid IMT
      (0.64 +/- 0.15 vs 0.57 +/- 0.12 mm), brachial IMT (1.02 +/- 0.25 vs 0.74 +/- 0.18
      mm), and aortic IMT (0.31 +/- 0.09 vs 0.26 +/- 0.04 mm) were significantly
      increased, and brachial FMD was significantly impaired (6.3 +/- 5.0 vs 9.7 +/-
      3.9%) in Fabry patients compared to healthy controls (p < 0.05 in all comparisons
      after adjustments for age, LDL-cholesterol, and systolic blood pressure). No
      differences were observed in arterial compliance between the groups. CONCLUSIONS:
      These data suggest that Fabry disease affects arterial function and structure by
      disturbing peripheral endothelial function and promoting intima-media thickening.

PMID- 16906475
TI  - Dramatic reduction in self-injury in Lesch-Nyhan disease following S
      adenosylmethionine administration.
AB  - A man with Lesch-Nyhan disease (LND; OMIM 300322) experienced significantly
      reduced self-injury and improved comfort while receiving S-adenosylmethionine.

PMID- 16906476
TI  - A novel indoloquinoline derivative, IQDMA, induces S-phase arrest and apoptosis
      in promyelocytic leukemia HL-60 cells.
AB  - N'-(11H-indolo[3,2-c]quinolin-6-yl)-N,N-dimethylethane-1,2-diamine (IQDMA), an
      indoloquinoline compound, was identified in our laboratory as a novel
      antineoplastic agent with a broad spectrum of antitumor activity against many
      human cancer cells. Cell cycle analysis showed S-phase arrest and induction of
      apoptosis in HL-60 cells following 24 h exposure to IQDMA. Analysis of the cell
      cycle regulatory proteins demonstrated that IQDMA did not change the steady-state
      levels of cyclin B1, cyclin D3, and p21, but decreased the protein levels of
      Cdk1, Cdk2, and cyclin A. IQDMA also caused a marked increase in apoptosis, which
      was accompanied by increased levels of Bax, activated caspase-3, -8, and -9, and
      cleaved PARP. These molecular alterations provide an insight into IQDMA-caused
      growth inhibition, S-phase arrest, and apoptotic death of HL-60 cells.

PMID- 16906477
TI  - Characterisation of two enteroviruses isolated from Australian brushtail possums
      (Trichosurus vulpecula) in New Zealand.
AB  - Two enteroviruses, designated W1 and W6, were isolated from intestinal contents
      of Australian brushtail possums (Trichosurus vulpecula) in New Zealand. The
      genomic sequences of W1 and W6 were 7390 and 7391 nucleotides (nt), respectively.
      Genetically, possum isolates W1 and W6 were related to bovine enterovirus
      serotype 2 (BEV-2) strains, especially to the strain PS87/Belfast, based on the
      capsid protein sequence. However, W1 and W6 formed a clade that was distinct from
      PS87Belfast based on nucleotide sequences of the 3' and 5'-non-translated region
      and in the amino acid sequences of 2A, 3C and 3D. Possum isolates W1 and W6 grew
      more readily in possum kidney cells than in Madin-Darby bovine kidney (MDBK)
      cells, suggesting that co-evolution of W1 and W6 with possums has made them more
      adapted to possum cells.

PMID- 16906478
TI  - Major rearrangements in the E element and minor variations in the U3 sequences of
      the avian leukosis subgroup J provirus isolated from field myelocytomatosis.
AB  - We collected paraffin-embedded myelocytomatoses induced by subgroup J avian
      leukosis virus (ALV-J) in French poultry from 1992 to 2000. We used nested PCR to
      obtain the U3 LTR and the E element sequences that encompass putative binding
      sites for transcription factors. We observed minor mutations in the U3 sequences
      that rarely affected transcription factor binding sites, thus preserving the
      transcriptional potential of the U3 LTR. However, we observed a large variability
      in the E element sequences from both field and experimental tumor samples. This
      variability involved genomic rearrangements and various deletions that most often
      occurred between two direct repeat sequences. Moreover, in seven DNA samples of
      the 22 field tumors analyzed, we observed two different sequences for the E
      element region, suggesting that proviral genomes of two different sizes may be
      simultaneously present in a tumor. Even though most of the E element sequences
      were mutated or rearranged, all myelocytomatosis samples always exhibited one E
      element sequence containing at least one putative C/EBP binding site that was
      unaffected and still potentially functional.

PMID- 16906479
TI  - PPARgamma agonism increases rat adipose tissue lipolysis, expression of glyceride
      lipases, and the response of lipolysis to hormonal control.
AB  - AIMS/HYPOTHESIS: The aim of this study was to investigate the effect and
      mechanisms of action of in vivo peroxisome proliferator-activated receptor gamma
      (PPARgamma) activation on white adipose tissue (WAT) lipolysis and NEFA
      metabolism. MATERIALS AND METHODS: Study rats were treated for 7 days with 15
      mg/kg of rosiglitazone per day; control rats were not treated. After a 6-h fast,
      lipolysis and levels of mRNA for lipases were assessed in explants from various
      adipose depots. RESULTS: Rosiglitazone markedly increased basal and noradrenaline
      (norepinephrine)-stimulated glycerol and NEFA release from WAT explants, and
      amplified their inhibition by insulin. Primary adipocytes isolated from PPARgamma
      agonist-treated rats were also more responsive to noradrenaline stimulation
      expressed per cell, ruling out a contribution of an altered number of mature
      adipocytes in explants. Rosiglitazone concomitantly increased levels of mRNA
      transcripts for adipose triglyceride lipase (ATGL) and monoglyceride lipase (MGL)
      in subcutaneous and visceral WAT, and mRNA for hormone-sensitive lipase (HSL) in
      subcutaneous WAT. Lipase expression increased within 12 h of in vitro exposure of
      naive explants to rosiglitazone, suggesting direct transcriptional activation. In
      parallel, chronic in vivo treatment with rosiglitazone lowered plasma NEFAs and
      in WAT its expected stimulatory action on glycerol and NEFA recycling, and on the
      expression of genes involved in NEFA uptake and retention by WAT, such processes
      counteracting net NEFA export. CONCLUSIONS/INTERPRETATION: These findings
      demonstrate that, in the face of its plasma NEFA-lowering action, PPARgamma
      agonism stimulates WAT lipolysis, an effect that is compensated by lipid
      retaining pathways. The results further suggest that PPARgamma agonism stimulates
      lipolysis by increasing the lipolytic potential, including the expression levels
      of the genes encoding adipose triglyceride lipase and monoglyceride lipase.

PMID- 16906480
TI  - Intratumor genomic heterogeneity in breast cancer with clonal divergence between
      primary carcinomas and lymph node metastases.
AB  - Conflicting theories of epithelial carcinogenesis disagree on the clonal
      composition of primary tumors and on the time at which metastases occur. In order
      to study the spatial distribution of disparate clonal populations within breast
      carcinomas and the extent of the genetic relationship between primary tumors and
      regional metastases, we have analyzed by comparative genomic hybridization 122
      tissue samples from altogether 60 breast cancer patients, including 34 tumor
      samples obtained from different quadrants of 9 breast carcinomas, as well as
      paired primary-metastatic samples from 12 patients. The median intratumor genetic
      heterogeneity score (HS) was 17.4% and unsupervised hierarchical clustering
      analysis comparing the genetic features to those of an independent series of 41
      breast carcinomas confirmed intratumor clonal divergence in a high proportion of
      cases. The median HS between paired primary breast tumors and lymph node
      metastases was 33.3%, but the number of genomic imbalances did not differ
      significantly. Clustering analysis confirmed extensive clonal divergence between
      primary carcinomas and lymph node metastases in several cases. In the independent
      series of 41 breast carcinomas, the number of genomic imbalances in primary
      tumors was significantly higher in patients presenting lymph node metastases
      (median = 15.5) than in the group with no evidence of disease spreading at
      diagnosis (median = 5.0). We conclude that primary breast carcinomas may be
      composed of several genetically heterogeneous and spatially separated cell
      populations and that paired primary breast tumors and lymph node metastases often
      present divergent clonal evolution, indicating that metastases may occur
      relatively early during breast carcinogenesis.

PMID- 16906481
TI  - Concepts and approaches towards understanding the cellular redox proteome.
AB  - The physiological activity of a significant subset of cell proteins is modified
      by the redox state of regulatory thiols. The cellular redox homeostasis depends
      on the balance between oxidation of thiols through oxygen and reactive oxygen
      species and reduction by thiol-disulfide transfer reactions. Novel and improved
      methodology has been designed during recent years to address the level of
      thiol/disulfide regulation on a genome-wide scale. The approaches are either
      based on gel electrophoresis or on chromatographic techniques coupled to high end
      mass spectrometry. The review addresses diagonal 2D-SDS-PAGE, targeted
      identification of specific redox-interactions, affinity chromatography with
      thioredoxins and glutaredoxins, gel-based and non-gel based labelling techniques
      with fluorophores (such as Cy3, Cy5, ICy), radioisotopes, or with isotope-coded
      affinity tags (ICAT), differential gel electrophoresis (DIGE) and combined
      fractional diagonal chromatography (COFRADIC). The extended methodological
      repertoire promises fast and new insight into the intricate regulation network of
      the redox proteome of animals, bacteria, and plants.

PMID- 16906482
TI  - Diverse functions and molecular properties emerging for CAX cation/H+ exchangers
      in plants.
AB  - Steep concentration gradients of many ions are actively maintained, with lower
      concentrations typically located in the cytosol, and higher concentrations in
      organelles and outside the cell. The vacuole is an important storage organelle
      for many ions. The concentration gradient of cations is established across the
      plant tonoplast, in part, by high-capacity cation/H+ (CAX) exchange activity.
      While plants may not be green yeast, analysis of CAX regulation and substrate
      specificity has been greatly aided by utilizing yeast as an experimental tool.
      The basic CAX biology in ARABIDOPSIS has immediate relevance toward understanding
      the functional interplay between diverse transport processes. The long-range
      applied goals are to identify novel transporters and express them in crop plants
      in order to "mine" nutrients out of the soil and into plants. In doing so, this
      could boost the levels of essential nutrients in plants.

PMID- 16906483
TI  - Development of NaCl-tolerant strain in Chrysanthemum morifolium Ramat. through in
      vitro mutagenesis.
AB  - One NaCl-tolerant chrysanthemum (Chrysanthemum morifolium Ramat.) variant (E2)
      has been developed in a stable form through IN VITRO mutagenesis using
      ethylmethane sulfonate (EMS) as the chemical mutagen. Salt tolerance was
      evaluated by the capacity of the plant to maintain both flower quality and yield
      under stress conditions. Enhanced tolerance of the E2 variant has been attributed
      to the increased activity of superoxide dismutase (SOD), ascorbate peroxidase
      (APX), and dehydroascorbate reductase (DHAR), and, to a lesser extent of membrane
      damage than NaCl-treated control plants. Isoform analysis revealed that an
      increase in total SOD activity in the E2 variant was solely due to significant
      activation of the Cu/Zn isoform. Elevated levels of carotenoids and ascorbate in
      E2 leaves have been reflected in their higher free radical scavenging capacity
      (RSC) expressed in terms of DPPH (2,2-diphenyl-1-picrylhydrazyl) scavenging
      ability. Data reflect that a proper balance between enzymatic and non-enzymatic
      defence systems is required for combating salinity stress in chrysanthemum.
      Better performance of the E2 progeny under same salinity stress condition, even
      in the second year, confirms the genetic stability of the salt-tolerance
      character. On the whole, the E2 variant, developed through 0.025 % EMS treatment,
      might be considered as a NaCl-tolerant strain showing positive characters towards
      NaCl stress.

PMID- 16906484
TI  - Seasonal profiles of sulphur, phosphorus, and potassium in Norway spruce wood.
AB  - Seasonal profiles of sulphur, phosphorus, and potassium content in the wood of
      trees have been established for the first time. This became possible by using a
      novel laser ablation system coupled to HR-ICP-MS for measuring these elements in
      Norway spruce drill cores. This technique combines excellent spatial resolution
      with superior detection power, and makes it possible to measure low element
      concentrations even in relatively narrow annual rings. Despite its low quantity
      in wood, sulphur is an important macronutrient for plants and seems to display
      seasonal variations of its concentration, which correspond to actual theories of
      sulphur metabolism in plants. A similar seasonal pattern was also found for
      phosphorus, another crucial element in tree nutrition. This was unexpected,
      because it was previously assumed that the distribution of phosphorus remains
      constant throughout the year. Potassium, the third element measured, seems to be
      especially accumulated in the latewood. The profiles presented in this article
      suggest a seasonal variation, revealing some new aspects of Norway spruce (PICEA
      ABIES) metabolism.

PMID- 16906485
TI  - Karyotype studies in South American species of Solanum subgen. Leptostemonum
      (Solanaceae).
AB  - Mitotic chromosome numbers and karyotypes of 13 South American species (12 native
      and one naturalized) from four sections of SOLANUM subgen. LEPTOSTEMONUM were
      studied. Chromosome numbers of S. ACERIFOLIUM, S. AENICTUM, S. CONDITUM, S.
      CONSIMILE, S. INCARCERATUM, and S. PLATENSE are reported for the first time. The
      number 2n = 24 was found in most species, while 2n = 22 was found in S. MAMMOSUM
      and S. PLATENSE. The latter is the second SOLANUM with this unusual number.
      Satellites are always present and were visible in more than 50 % of the cells
      studied. Karyotypes are symmetrical: M and SM chromosomes are common, whereas ST
      chromosomes are rare. The karyotypes of S. AENICTUM, S. MAMMOSUM, and S.
      PANICULATUM are comparatively asymmetrical. Species can be distinguished by a
      combination of chromosome number, karyotype formulae, karyotype length, the
      position of satellites in a particular chromosome pair, and asymmetry indices.
      The phenogram obtained does not reflect the sectional arrangements or the
      systematic affinities of the species studied. In sect. ACANTHOPHORA, increased
      asymmetry is associated with derived characters (strong andromonoecy, winged
      seeds, mammiform fruits). Diversification in the subgenus is suggested to be
      related to visible chromosome rearrangements and cumulative, cryptic structural
      changes may have also played a relevant evolutionary role.

PMID- 16906486
TI  - At daybreak--reproductive biology and isolating mechanisms of Cirrhaea dependens
      (Orchidaceae).
AB  - Floral biology, reproduction, pollinator specificity, and fruit set of Cirrhaea
      dependens were recorded in forest areas of Southeastern Brazil. Cirrhaea
      dependens is a lithophytic or epiphytic herb occurring very sparsely below dense
      canopies. Nearly all the flowers of a single plant open simultaneously before
      dawn. They are short-lasting and offer floral fragrances as rewards, which are
      collected by male euglossine bees. Observations carried out in mesophytic forests
      at Serra do Japi revealed that Euglossa VIRIDIS is their principal pollinator,
      with Eufriesea violacea a sporadic co-pollinator. Visitation started soon after
      flower opening, and attractiveness remained high for about 2 h, decreasing
      abruptly at sunrise. Flower anthesis with subsequent fragrance release seems to
      be correlated with bee attraction. Observations using chemical baits were carried
      out at Serra do Japi, and in the Atlantic Rain Forest of Picinguaba. Three
      euglossine species were captured with pollinaria of C. dependens in Picinguaba,
      whereas only E. violacea was attracted in Serra do Japi. In Picinguaba, C.
      dependens occurs sympatrically with C. saccata and C. loddigesii. Each species
      attracted different pollinators. The specificity and resulting reproductive
      isolation are due to the production of different odours by each orchid species.
      Cirrhaea dependens is self-compatible but pollinator-dependent. The reproductive
      success was low and appears to result from a combination of factors discussed
      here, such as the production of short-lived flowers, presence of floral
      mechanisms avoiding self-pollination, non-synchronization of flower phases among
      plants, and populations with few and sparsely distributed individuals.

PMID- 16906487
TI  - Analysis of competition effects in mono- and mixed cultures of juvenile beech and
      spruce by means of the plant growth simulation model PLATHO.
AB  - Inter- and intra-specific competition between plants for external resources is a
      critical process for plant growth in natural and managed ecosystems. We present a
      new approach to simulate competition for the resources light, water, and nitrogen
      between individual plants within a canopy. This approach was incorporated in a
      process-oriented plant growth simulation model. The concept of modelling
      competition is based on competition coefficients calculated from the overlap of
      occupied crown and soil volumes of each plant individual with the occupied
      volumes of its four nearest neighbours. The model was parameterised with data
      from a two-year phytotron experiment with juvenile beech and spruce trees growing
      in mono- and mixed cultures. For testing the model, an independent data set from
      this experiment and data from a second phytotron experiment with mixed cultures
      were used. The model was applied to analyse the consequences of start conditions
      and plant density on plant-plant competition. In both experiments, spruce
      dominated beech in mixed cultures. Based on model simulations, we postulate a
      large influence of start conditions and stand density on the outcome of the
      competition between the species. When both species have similar heights at the
      time of canopy closure, the model suggests a greater morphological plasticity of
      beech compared with spruce to be the crucial mechanism for competitiveness in
      mixed canopies. Similar to the experiment, in the model greater plasticity was a
      disadvantage for beech leading to it being outcompeted by the more persistent
      spruce.

PMID- 16906488
TI  - Stomatal conductance is a key parameter to assess limitations to photosynthesis
      and growth potential in barley genotypes.
AB  - Fourteen genotypes of barley were compared for response to salinity by monitoring
      the parameters gas exchange and chlorophyll fluorescence. We present
      relationships between stomatal conductance (gs) gas exchange chlorophyll
      fluorescence parameters and aboveground dry matter (AGDM). We found that genetic
      variability provided a continuum of data for gs across control and saline
      conditions. We used this continuum of gs values to test the overall relationships
      between gs and net photosynthesis (A), leaf internal CO2 concentration (Ci),
      actual quantum yield of PSII electron transport (PhiPSII), relative electron
      yield over net CO2 assimilation rate (ETR/A), and AGDM. The relationship between
      gs and A was highly significant (P < 0.0001) for both control and saline
      treatments, while correlations between gs and Ci, and Ci and A were significant
      only under control conditions. Unexpectedly, we found positive correlations
      between gs and PhiPSII (P < 0.0001) for both conditions. A comparison between
      relationships of gs and A, and gs and PhiPSII seemed to indicate a possible
      acclimation to salinity at the chloroplastic level. Finally, the relationships
      between gs and ETR/A were exceptionally strong for both growing conditions (P <
      0.0001) indicating that, as gs values were negatively affected in barley by
      genetics and salinity as main or interactive effects, there was a progressive
      increase in photorespiration in barley. Overall, we found that stomatal
      conductance was a key parameter in the study of barley responses to limiting
      situations for photosynthesis. We also found a strong relationship between AGDM
      and gs regardless of growing conditions and genotypes. For breeding evaluations
      to select barley genotypes for salinity tolerance, it may be possible to replace
      all measurements of gas exchange and chlorophyll fluorescence by the simple use
      of a porometer.

PMID- 16906489
TI  - Caladium bicolor (Araceae) and Cyclocephala celata (Coleoptera, Dynastinae): a
      well-established pollination system in the Northern Atlantic rainforest of
      Pernambuco, Brazil.
AB  - Flowering, pollination ecology, and floral thermogenesis of Caladium bicolor were
      studied in the Atlantic Rainforest of Pernambuco, NE Brazil. Inflorescences of
      this species are adapted to the characteristic pollination syndrome performed by
      Cyclocephalini beetles. They bear nutritious rewards inside well-developed floral
      chambers and exhibit a thermogenic cycle which is synchronized to the activity
      period of visiting beetles. Heating intervals of the spadix were observed during
      consecutive evenings corresponding to the beginning of the female and male phases
      of anthesis. Highest temperatures were recorded during the longer-lasting female
      phase. An intense sweet odour was volatized on both evenings. Beetles of a single
      species, Cyclocephala celata, were attracted to odoriferous inflorescences of C.
      bicolor and are reported for the first time as Araceae visitors. All the
      inflorescences visited by C. celata developed into infructescences, whereas
      unvisited inflorescences showed no fruit development. Findings of previous
      studies in the Amazon basin of Surinam indicated that Cyclocephala rustica is a
      likely pollinator of C. bicolor. This leads to the assumption that locally
      abundant Cyclocephalini species are involved in the pollination of this species.

PMID- 16906490
TI  - Phase II trial designs in the presence of stratification.

PMID- 16906491
TI  - Circular dichroism as a reliable tool for anomeric assignment of glycosyl-2
      phenyl-2H-1,2,3-triazole C-nucleoside analogs. A rule for prediction of their
      anomeric configuration.
AB  - The circular dichroism (CD) of a series of acyclic C-nucleoside analogs; 4
      (pentahydroxypentyl-1-yl)-2-phenyl-2H-1,2,3-triazoles [1-5] and 4-(D-glycero-D
      gulo)-2-phenyl-2H-1,2,3-triazole 6, are reported. A correlation between the sign
      of the Cotton effect at the maximal UV absorption and the absolute configuration
      of the carbon atom alpha- to the triazole base moiety is reported. The CD of
      anomeric 4-(alpha,beta-D-arabinofuranosyl)- and 4-(alpha,beta-D-arabinopyranosyl)
      2-phenyl-2H-1,2,3-triazole C-nucleosides are reported. The assignment of the
      anomeric configuration of C-glycosyl-2-phenyl-2H-1,2,3-triazoles from their CD
      spectra was found to be a simple method that relies on comparison of the sign of
      the Cotton effect at the maximal UV absorption and the absolute configuration of
      the anomeric carbon atom. A correlation between the anomeric configuration and
      the sign of the Cotton effect at the maximal UV absorption is deduced and
      generalized as a rule for prediction of the anomeric configuration of C-glycosyl
      2-phenyl-2H-1,2,3-triazoles. Nuclear Overhauser effect and 13C NMR spectra
      supported the CD assignment rule.

PMID- 16906492
TI  - Chirality of camphor derivatives by density functional theory.
AB  - Infrared (IR) and vibrational circular dichroism (VCD) spectra of chiral camphor,
      camphorquinone and camphor-10-sulfonic acid (CSA), known as standard compounds
      for electronic circular dichroism (ECD) spectroscopy, are measured and their
      vibrational frequencies, infrared intensities, and rotational strengths are
      calculated using density functional theory (DFT). The observed IR and VCD spectra
      of chiral camphor and camphorquinone in carbon tetrachloride solution are
      reproduced by the DFT calculations, but those of CSA are not. DFT calculations of
      hydration models, where an anionic CSA specifically binds a few water molecules,
      are carried out. The average of the simulated VCD spectra in the hydration models
      is more consistent with the observed spectra. In addition, the wavelengths and
      dipole and rotational strengths for chiral camphor, camphorquinone, anionic CSA,
      and the hydration models were calculated by time-dependent DFT. In the region of
      280-300 nm, the calculated wavelengths of the ECD bands for chiral camphor and
      camphorquinone coincide with the observed wavelengths that have been reported,
      and the calculated wavelengths for the hydration models are closer to the
      observed wavelengths reported than are those calculated for chiral anionic CSA.
      Consequently, the analysis combined with VCD and ECD spectroscopy using DFT
      calculations can elucidate the chirality of optically active molecules, even in
      an aqueous solution.

PMID- 16906493
TI  - Stereoselective pharmacokinetics of ornidazole after intravenous administration
      of individual enantiomers and the racemate.
AB  - The pharmacokinetics of ornidazole (ONZ) were investigated following i.v.
      administration of racemic mixture and individual enantiomers in beagle dogs.
      Plasma concentrations of ONZ enantiomers were analyzed by chiral high-performance
      liquid chromatography (HPLC) on a Chiralcel OB-H column with quantification by UV
      at 310 nm. Notably, the mean plasma levels of (-)-ONZ were higher in the
      elimination phase than those of (+)-ONZ. (-)-ONZ also exhibited greater t1/2,
      MRT, AUC(0-t) and smaller CL, than those of its antipode. The area under the
      plasma concentration-time curve (AUC(0-t)) of (-)-ONZ was about 1.2 times as high
      as that of (+)-ONZ. (+)-ONZ total body clearance (CL) was 1.4 times than its
      optical antipode. When given separately, there were significant differences in
      the values of AUC(0-infinity) and CL between ONZ enantiomers (P < 0.05),
      indicating that elimination of (+)-ONZ was more rapid than that of (-)-ONZ. No
      significant differences were found between the estimates of the pharmacokinetic
      parameters of (+)-ONZ or (-)-ONZ, obtained following administration as the
      individual and as a racemic mixture. This study demonstrates that the elimination
      of ONZ enantiomers is stereoselective and chiral inversion and
      enantiomer/enantiomer interaction do not occur when the enantiomers are given
      separately and as racemic mixture.

PMID- 16906494
TI  - Fourier transform near-infrared vibrational circular dichroism used for on-line
      monitoring the epimerization of 2,2-dimethyl-1,3-dioxolane-4-methanol: A pseudo
      racemization reaction.
AB  - Near-infrared (near-IR) Fourier transform vibrational circular dichroism (FT-VCD)
      spectroscopy has been used to monitor the epimerization of (S)-(+)-2,2-dimethyl
      1,3-dioxolane-4-methanol (S-DDM). The near-IR-VCD spectra display clear isolated
      VCD bands at the range of 4700-5050 cm(-1) resulting from the OH stretch-bend
      combination bands of S-DDM, which were found to decrease in intensity with
      increasing reaction time. The near-IR-VCD spectra of 10 reference samples
      obtained were subjected to partial least-squares (PLS) regression analysis, and
      the results were used to build predictive models for enantiomeric excess (EE)
      determination. Multivariate regression was carried out on three different sets of
      spectra, corresponding to the epimerization of S-DDM in three different solvents:
      methylcyclohexane, carbon tetrachloride and tetrahydrofuran. The effects of
      solvent in DDM epimerization are discussed in terms of the relative stabilization
      of the reaction intermediate of the DDM epimerization reaction. The results of
      these near-IR-VCD studies for the determination of EE highlights the potential of
      VCD for in situ real-time process monitoring of the reaction kinetics of chiral
      molecules in solution.

PMID- 16906495
TI  - Antibiotic resistance: mono- and dinuclear zinc complexes as metallo-beta
      lactamase mimics.
AB  - Biomimetic systems containing one or two zinc(II) ions supported by phenolate
      ligands were developed as functional mimics of metallo-beta-lactamase. These
      complexes were shown to catalytically hydrolyze beta-lactam substrates, such as
      oxacillin and penicillin G. The dinuclear zinc complex 1, which has a coordinated
      water molecule, exhibits high beta-lactamase activity, whereas the dinuclear zinc
      complex 2, which has no water molecules, but labile chloride ligands, shows a
      much lower activity. The high beta-lactamase activity of complex 1 can be
      ascribed to the presence of a zinc-bound water molecule that is activated by
      being hydrogen bonded to acetate substituents. The kinetics of the hydrolysis of
      oxacillin by complex 1 and the effect of pH on the reaction rates are reported in
      detail. In addition, the kinetic parameters obtained for the synthetic analogues
      are compared with those of the natural metallo-beta-lactamase from Bacillus
      cereus (BcII). To understand the role of the second metal ion in hydrolysis, the
      syntheses and catalytic activities of two mononuclear complexes (3 and 4) that
      include coordinated water molecules are described. Interestingly, the mononuclear
      zinc complexes 3 and 4 also exhibit high activity, supporting the assumption that
      the second zinc ion is not crucial for the beta-lactamase activity.

PMID- 16906497
TI  - Cationic eta(1)/eta(2)-gold(I) complexes of simple arenes.

PMID- 16906498
TI  - A priori theoretical prediction of selectivity in asymmetric catalysis: design of
      chiral catalysts by using quantum molecular interaction fields.

PMID- 16906500
TI  - Toward the total synthesis of spirastrellolide A. Part 2: Conquest of the
      northern hemisphere.

PMID- 16906502
TI  - Use of triplet excited States for the study of drug binding to human and bovine
      serum albumins.
AB  - The triplet excited states of (S)- and (R)-flurbiprofen (FBP) have been used as
      reporters for the microenvironments experienced within the binding sites of human
      and bovine serum albumins. Regression analysis of triplet decay provides valuable
      information on the degree of protection that these excited states are afforded
      from attack by a second FBP molecule, oxygen, or other reagents. The
      multiexponential fitting of these decays can be satisfactorily correlated with
      the distribution of the drug among the two binding sites and its presence as the
      noncomplexed form in the bulk solution. This assignment has been confirmed by
      using (S)-ibuprofen or capric acid as selective site II replacement probes.
      Triplet lifetimes and site occupancy are sensitive to the type of serum albumin
      employed (human versus bovine). Finally, the binding behaviour of (S)- and (R)
      FBP exhibits little stereoselectivity.

PMID- 16906503
TI  - Multiparallel chiral method development screening using an 8-channel microfluidic
      HPLC system.
AB  - The Eksigent Express 800 8-channel microfluidic HPLC system was investigated for
      carrying out multiparallel screening and development of fast normal phase chiral
      separations. In contrast to the familiar automated sequential chiral method
      development approaches that often afford a next day result, the multiparallel
      approach offers the exciting possibility of near "real time" method development,
      often affording an optimized method in less than 1 h. In this study, four column
      types (300 microm i.d.) with two different mobile phases are screened using a
      universal standard gradient approach. Interestingly, parallel method optimization
      following initial screening was shown to sometimes lead to surprising and
      unanticipated outcomes, emphasizing the value of the multiparallel screening
      approach. A variety of standard test racemates were analyzed, with optimized
      separation methods for most in the 1- to 2-min range. These results compare
      favorably with results obtained on a single channel conventional HPLC system
      using 4.6-mm i.d. columns. In addition, isocratic methods developed on the
      microbore columns are readily translated to the larger column format.

PMID- 16906504
TI  - Comparing the impact of conventional pesticide and use of a transgenic pest
      resistant crop on the beneficial carabid beetle Pterostichus melanarius.
AB  - The potential impact of a chemical pesticide control method has been compared
      with that of transgenic plants expressing a protease inhibitor conferring insect
      resistance by utilising a tritrophic system comprising the crop plant Brassica
      napus (L.) (Oilseed rape), the pest mollusc Deroceras reticulatum (Muller) and
      the predatory carabid beetle Pterostichus melanarius (Illiger). Cypermethrin, as
      the most widely used pesticide in UK oilseed rape (OSR) cultivation, was selected
      as the conventional treatment. OSR expressing a cysteine protease inhibitor,
      oryzacystatin-1 (OC-1), was the transgenic comparator. In feeding trials, D.
      reticulatum showed no significant long-term effects on measured life history
      parameters (survival, weight gain, food consumption) as a result of exposure to
      either the cypermethrin or OC-1 treatment. However, D. reticulatum was able to
      respond to the presence of the dietary inhibitor by producing two novel proteases
      following exposure to OC-1-expressing OSR. Similarly, P. melanarius showed no
      detectable alterations in mortality, weight gain or food consumption when feeding
      on D. reticulatum previously fed either pesticide-contaminated or GM plant
      material. Furthermore, as with the slug, a novel form of protease, approximately
      M(r) 27 kDa, was induced in the carabid in response to feeding on slugs fed OC-1
      expressing OSR.

PMID- 16906507
TI  - Adolescents and young adults with cancer: the scope of the problem and
      criticality of clinical trials.
AB  - In the U.S., older adolescents and young adults with cancer have benefited less
      from therapeutic advances than did either younger or older patients. One factor
      that may explain this deficit is the relative lack of participation of patients
      in this age group on clinical trials of therapies that could improve their
      outcome. Comparisons were made of the participation of cancer patients on
      clinical trials in the U.S., as a function of patient age, with the change in
      national cancer mortality rate; and Surveillance, Epidemiology, End Results
      (SEER) cancer survival rate as a function of age. The participation rate in
      cancer treatment trials has been strikingly lower in 15-34-year-olds than in
      younger or older patients. The nadir has been apparent for both males and females
      in all of the major ethnic and racial groups. The national cancer mortality
      reduction and SEER survival improvement shows a similar age dependence. In the
      U.S., the age-dependence of cancer treatment trial participation, and of
      improvement in survival prolongation and cancer death rates, are correlated.
      Regardless of whether there is a causal relationship, the impact on the older
      adolescent and young adult U.S. population is substantial, adversely affecting
      the national cost of healthcare, the person-years of life lost, the loss of young
      people entering the job market, and the scientific knowledge and social
      implications of cancer during adolescence and early adulthood. National
      initiatives are underway to address these issues, with special emphasis on
      increasing the availability and access to clinical trials designed for older
      adolescents and young adults.

PMID- 16906506
TI  - Poly (ADP-ribose) polymerase (PARP) is essential for sulfur mustard-induced DNA
      damage repair, but has no role in DNA ligase activation.
AB  - Concurrent activation of poly (ADP-ribose) polymerase (PARP) and DNA ligase was
      observed in cultured human epidermal keratinocytes (HEK) exposed to the DNA
      alkylating compound sulfur mustard (SM), suggesting that DNA ligase activation
      could be due to its modification by PARP. Using HEK, intracellular 3H-labeled
      NAD+ (3H-adenine) was metabolically generated and then these cells were exposed
      to SM (1 mM). DNA ligase I isolated from these cells was not 3H-labeled,
      indicating that DNA ligase I is not a substrate for (ADP-ribosyl)ation by PARP.
      In HEK, when PARP was inhibited by 3-amino benzamide (3-AB, 2 mM), SM-activated
      DNA ligase had a half-life that was four-fold higher than that observed in the
      absence of 3-AB. These results suggest that DNA repair requires PARP, and that
      DNA ligase remains activated until DNA damage repair is complete. The results
      show that in SM-exposed HEK, DNA ligase I is activated by phosphorylation
      catalysed by DNA-dependent protein kinase (DNA-PK). Therefore, the role of PARP
      in DNA repair is other than that of DNA ligase I activation. By using the DNA
      ligase I phosphorylation assay and decreasing PARP chemically as well as by PARP
      anti-sense mRNA expression in the cells, it was confirmed that PARP does not
      modify DNA ligase I. In conclusion, it is proposed that PARP is essential for
      efficient DNA repair; however, PARP participates in DNA repair by altering the
      chromosomal structure to make the DNA damage site(s) accessible to the repair
      enzymes.

PMID- 16906508
TI  - Sexual health and self-esteem in adolescents and young adults with cancer.
AB  - A diagnosis of cancer compounds the complexities of adolescent development. Self
      esteem and sexual health have a significant impact on adolescent identity
      formation, especially those young patients coping with a diagnosis of cancer.
      Knowledge of sexual health, interpersonal relationships, and body image concerns
      are factors that have an impact on the development of self-esteem during these
      transition periods into adulthood. A clinical perspective on these issues was
      utilized to highlight the nature of self-esteem and sexuality in adolescents and
      young adults with cancer. Case examples and clinical recommendations from a
      workshop on self-esteem and sexuality in adolescents and young adults with cancer
      are presented. Understanding the adolescent's and young adult's stage of identity
      formation, their social and developmental histories, and methods for increasing
      self-esteem can give insight to healthcare professionals in fostering positive
      self-esteem and sexual health in these young patients. Through the awareness of
      the specific factors affecting adolescents and young adults with cancer, oncology
      teams can assist in creating an atmosphere for the growth of positive self-esteem
      and sexual health in their adolescent patients.

PMID- 16906509
TI  - Proceedings of a workshop: bridging the gap in care and addressing participation
      in clinical trials.
AB  - The purpose of this workshop was to examine possible strategies for increasing
      participation by adolescent and young adult cancer patients in clinical trials.
      Three key established issues set the framework for this discussion: 1) In the
      United States, individuals in the 15-40 age group are less likely than either
      children or older adults to be referred to a comprehensive cancer center. 2)
      Enrollment in therapeutic clinical trials is unacceptably low among adolescent
      and young adult patients everywhere this has been studied, including United
      States, Canada, and United Kingdom. 3) Cancers that occur in patients in this age
      group with particular frequency (notably malignant lymphomas and bone tumors)
      have relatively long intervals from symptom onset to diagnosis (POG 9082). This
      may reflect both distinct biologic features of these diseases and a real gap in
      health care.

PMID- 16906510
TI  - Visualization of MAPT inversion on stretched chromosomes of tau-negative
      frontotemporal dementia patients.

PMID- 16906511
TI  - Radiation-induced xerostomia.
AB  - BACKGROUND: Radiation-induced xerostomia is a frequent and usually permanent side
      effect of radiation therapy for head and neck cancer. We summarize recent
      developments in the prevention and treatment of radiation-induced xerostomia.
      METHODS: The Medline database was searched for articles published within the past
      10 years on the prevention and treatment of postirradiation xerostomia.
      Proceedings of recent important national meetings and government Web registries
      of clinical trials and therapeutic agents were also consulted. Priority was given
      to randomized controlled trials but, because of the scarcity of such trials,
      small open trials were included in this review. No other predetermined selection
      criteria were used, although articles exploring the effects of xerostomia and its
      treatment on quality of life were considered of special interest. RESULTS: A
      variety of preventive approaches for postirradiation xerostomia exist, involving
      more conformal radiation delivery technology, radioprotective agents, and even
      preirradiation surgical techniques. Therapeutic interventions include supportive
      care, saliva supplementation, and the use of pro-cholinergic salivary
      secretagogues. CONCLUSIONS: Radiation-induced xerostomia constitutes a
      significant morbidity after orofacial irradiation. Careful preventive techniques,
      meticulous supportive care, and new preventive and therapeutic agents may prove
      useful in combination.

PMID- 16906512
TI  - Efficacy and safety of ultrasonically activated shears in thyroid surgery.
AB  - BACKGROUND: The purpose of this prospective study is to evaluate the efficacy of
      ultrasonically activated shears (UAS) in hemostasis as well as its safety in
      regard to complications in thyroid surgery. METHODS: Three hundred patients who
      had undergone surgery on the thyroid gland were divided into 2 groups of 150
      patients each. Hemostasis as well as division of blood vessels and thyroid tissue
      were performed with the use of UAS in the first group and by conventional
      ligations in the second group. RESULTS: The use of UAS resulted in as much as a
      39.7% reduction in the operative time of the total thyroidectomy and a 30.8%
      reduction of the lobectomy (p < .001). However, there was no important difference
      in the postoperative blood loss in either the temporary hypoparathyroidism or the
      paresis of recurrent laryngeal nerves. CONCLUSIONS: The use of UAS in thyroid
      surgery is a safe method for hemostasis, as well as for the division of blood
      vessels and thyroid tissue. It leads to the reduction of the total operative time
      without serious complications.

PMID- 16906513
TI  - Nutritional factors and survival of patients with oral cancer.
AB  - BACKGROUND: Our objective was to determine the survival rate of patients with
      oral cancer who were treated at a medical center in central Taiwan. Furthermore,
      we attempted to investigate whether nutritional factors influence the survival.
      METHODS: We carried out a retrospective review of 1010 chart records of patients
      with oral cancer. We used the Kaplan-Meier method for survival analysis and the
      Cox proportional hazard models to investigate the prognosticators. RESULTS:
      Kaplan-Meier survival analysis showed an overall 5-year survival rate of 63.24%.
      The Cox proportional hazard model revealed that those with a preoperative body
      mass index (BMI) of <22.8 kg/m(2) tended to have a higher probability of death
      (relative risk [RR] = 1.292, p = .022). In addition, those with a preoperative
      serum albumin level of <4.15 g/dL were generally associated with a poorer
      prognosis (RR = 1.313, p = .016). CONCLUSIONS: Apart from clinical features,
      nutritional factors also had a significant influence on the survival of patients
      with oral cancer. Therefore, good nutritional status is crucial for patients with
      oral cancer in improving their survival.

PMID- 16906514
TI  - Malignant blue nevus of the parotid gland: A case report.
AB  - BACKGROUND: Malignant blue nevus is a highly aggressive tumor arising from a
      background of benign blue nevus. Extensive review of the medical literature
      revealed a few reported cases of this transformation from cutaneous origin. We
      report the first case of blue nevus of the parotid gland and its malignant
      transformation within this gland. METHODS: A 62-year-old woman presented to our
      clinic with sudden onset parotid mass. After a superficial parotidectomy,
      histologic examination of the specimen was performed. Features compatible with
      blue nevus with focal region of atypical mitotic activity were evident. The
      diagnosis of malignant blue nevus was confirmed by immunohistochemical studies.
      RESULTS: We report the first case of malignant transformation of blue nevus
      within the parotid gland. CONCLUSIONS: We found this lesion to be highly
      aggressive and to have metastasized shortly after diagnosis.

PMID- 16906515
TI  - Experimental results of the tracheoesophageal tissue connector for improved
      fixation of shunt valves in laryngectomized patients.
AB  - BACKGROUND: After total laryngectomy and voice rehabilitation using a
      tracheoesophageal shunt valve, patients often have valve-related complications
      such as leakage. To solve these problems, a tracheoesophageal tissue connector
      (TE-TC) was devised to serve as an interface between the patient's tissue
      (trachea and esophagus) and the shunt valve. METHODS: The TE-TC is a permucosal
      connection constructed from a titanium ring (filled with a silicon rubber plug)
      combined with polypropylene or titanium mesh. After implantation in adult goats
      for 12 weeks the implants were submitted to histologic investigation. RESULTS:
      Firm implant fixation was achieved. In nearly all (18/19), no signs of infection
      of the implant were seen; 11 of 19 animals died before the end of the experiment
      owing to complications not related to the implant. CONCLUSIONS: The TE-TC is a
      new device with potential in the solution for fixation-related problems in
      tracheoesophageal voice rehabilitation.

PMID- 16906516
TI  - Phenotype-genotype correlation: challenge of intestinal-type adenocarcinoma of
      the nasal cavity and paranasal sinuses.
AB  - BACKGROUND: Intestinal-type adenocarcinoma (ITAC) of the nasal cavity and
      paranasal sinuses shows microscopic features indistinguishable from colorectal
      cancer. Our aim was to verify whether the morphologic resemblances mirror genetic
      profile similarities. METHODS: Twenty consecutive surgically treated ITAC cases,
      previously investigated for p16(INK4a) and TP53, were investigated for hMLH1,
      hMSH2, and beta-catenin immunoreactivity, and for adenomatous polyposis coli
      (APC), K-ras, and BRAF gene mutations. RESULTS: One case was immunonegative for
      both hMLH1 and hMSH2, and 12 tumors (40%) revealed a strong beta-catenin
      overexpression. No BRAF and APC truncating mutations were identified, whereas K
      ras mutations were detected in 9 ITACs (50%). CONCLUSIONS: Our data confirm the
      phenotypic similarities at the genetic level between colorectal cancer and ITACs
      showing deregulation of K-Ras/BRAF and loss of heterozygosity (LOH) of chromosome
      18q. By contrast, both frequency rate and type of inactivation of the APC-beta
      catenin pathway differ in the 2 tumors, suggesting different gatekeeper events in
      the early development of ITAC (p16(INK4a) and TP53) and colorectal cancer (APC).

PMID- 16906517
TI  - Swallowing outcomes after radiotherapy for head and neck cancer: a systematic
      review.
AB  - BACKGROUND: A systematic review of the current data on swallowing function after
      radiotherapy or chemoradiotherapy is presented. METHODS: Electronic databases
      were searched for 1966-2005. Papers were categorized according to level of
      evidence, methodological quality, and the specific domain of swallowing being
      measured. RESULTS: Of 109 papers retrieved, 33 were identified and reviewed.
      Evidence was primarily classified as either level III.2 (cohort studies) or level
      IV (case series). Methodological quality was found to be compromised in most
      studies. Although many researchers had investigated swallowing impairment, a wide
      variety of measurement tools were employed. CONCLUSIONS: There are limited data
      on swallowing outcomes after radiotherapy or chemoradiotherapy for head and neck
      cancer. Further work is needed to ascertain which aspects of swallowing should be
      measured, and then to use such measures in well-designed clinical trials and
      prospective cohort studies of this under-researched population.

PMID- 16906518
TI  - Cystic fibrosis transmembrane conductance regulator (CFTR) dependent cytoskeletal
      tension during lung organogenesis.
AB  - There is growing evidence for the role of CFTR (cystic fibrosis transmembrane
      conductance regulator) in lung development and differentiation. The mechanism by
      which the chloride channel could affect lung organogenesis, however, is unknown.
      In utero CFTR gene transfer in the fetal lungs of mice, rats, and non-human
      primates was shown previously to alter lung structure and function. A study of
      the genes altered in the fetal rat lung following CFTR overexpression was
      initiated in an effort to determine the molecular mechanism for CFTR-dependent
      differentiation. In utero gene transfer with recombinant adenoviruses carrying
      either a reporter gene or CFTR resulted in the increased expression of a number
      of genes upon microarray analysis. The majority of the genes overexpressed in the
      CFTR-treated lungs were primarily associated with muscle structure and function.
      Histological and biochemical characterization of these proteins including myosin
      heavy chain, heat shock protein 27, and isoforms of myosin light chain showed
      that CFTR overexpression had a profound effect on smooth muscle contraction
      related proteins. The CFTR-dependent regulation of smooth muscle contraction
      related proteins was shown to be related to chloride and extracellular ATP and
      was dependent upon the PI3 Kinase and Phospholipase C pathways. The changes in
      smooth muscle proteins were consistent with CFTR-dependent contractions of the
      embryonic airway smooth muscle. An assay was developed using fluorescent
      polystyrene beads to show that CFTR did indeed increase amniotic fluid flow into
      the fetal lung. Increased amniotic fluid pressure was shown previously to be
      associated with stretch-induced differentiation of the lung. Evaluation of
      neonatal respiratory function showed that CFTR-dependent muscle contractions and
      increased amniotic fluid pressure resulted in accelerated maturation of the
      neonatal rat lung. In addition, these CFTR-dependent changes were shown to be
      sufficient to reverse the lung phenotype of the CFTR knockout mouse. Mechanical
      forces influence lung development through pulmonary distension. CFTR
      overexpression in the fetal lung altered differentiation and development in the
      lung. These results are consistent with CFTR influencing lung development by
      regulating the muscle contractions associated with cytoskeletal tension and
      stretch induced differentiation. Deficiency of CFTR altering lung development
      would contribute significantly to the Cystic Fibrosis disease phenotype.

PMID- 16906519
TI  - Mechanistic investigation on the cause for reduced toxicity of TCDD in wa-1
      homozygous TGFalpha mutant strain of mice as compared its matching wild-type
      counterpart, C57BL/6J mice.
AB  - We investigated the cause for resistance to TCDD toxicity in TGFalpha mutant wa-1
      mice (wa/wa) as compared to its wild-type C57BL/6J(+/+) counterpart. For this
      purpose after 1 or 10 days TCDD (115 microg/kg) exposure, liver samples were
      isolated. Biochemical investigations revealed that wa/wa mice showed decreased
      effects of TCDD characterized by reduced triglyceride accumulation and lesser
      declines in glycogen levels. qRT-PCR mRNA analysis demonstrated that while the
      effect of TCDD on EGF receptor and ERK-1 in wa/wa mice were indistinguishable
      from +/+ mice, upregulation by TCDD of c-Src and ERK-2 and downregulation of
      PEPCK were less pronounced in the wa/wa mice. To confirm that these differences
      are due to intrinsic cellular characteristics, mouse embryonic fibroblast (MEF)
      cells were cultured from embryos and their responses to 10 nM TCDD were assessed.
      qRT-PCR analysis showed that MEF from the wa/wa mice was less responsive to TCDD
      in terms of its stimulatory effect on ERK-2, but not on ERK-1. These results
      indicate that a possible mechanism why wa/wa mice are less responsive to TCDD is
      that two genes encoding for the growth factor signaling components, c-Src and ERK
      2, are not readily affected by TCDD.

PMID- 16906520
TI  - Decreasing expression of alpha1C calcium L-type channel subunit mRNA in rat
      ventricular myocytes upon manganese exposure.
AB  - Manganese is an essential trace element found in many enzymes. As it is the case
      of many essential trace elements, excessive level of manganese is toxic. It has
      been proven that excessive manganese could cause heart problems. In order to
      understand the mechanism of manganese toxicity in the heart, the effects of
      manganese on isolated rat ventricular myocytes were studied. The L-type calcium
      channel current was measured by whole-cell patch clamp recording mode. In the
      electrophysiology experiments, both 50 microM Mn2+ and 100 microM Mn2+ could
      effectively decrease the channel current amplitude density by 35.7% and 68.2%,
      respectively. Moreover, Mn2+ shifted the steady-state activation curve toward
      more positive potential and the steady-state inactivation curve toward more
      negative potential. Investigation by RT-PCR showed that the mRNA expression of
      alpha1C/Cav1.2 treated with manganese was decreased depending on its
      concentration, while the mRNA expression of alpha1D/Cav1.3 was almost unchanged.
      Fluo-3/AM was utilized for real-time free calcium scanning with laser scanning
      confocal microscopy (LSCM), and the results showed that Mn2+ could elicit a slow
      and continuous increase of [Ca2+]i in a concentration-dependent manner. These
      results have suggested that manganese could interfere with the function of the L
      type calcium channel, downregulate the mRNA expression of alpha1C/Cav1.2, and
      thus causing long-lasting molecular changes of L-type calcium channel which have
      probably been triggered by overloading of calcium in myocytes.

PMID- 16906521
TI  - Antilipoperoxidative and antioxidant effects of S-allyl cysteine sulfoxide on
      isoproterenol-induced myocardial infarction in Wistar rats.
AB  - Our study evaluates the preventive effect of S-allyl cysteine sulfoxide (SACS) on
      lipid peroxidative products and enzymic and nonenzymic antioxidants in
      isoproterenol (ISO) induced myocardial infarction in rats. The male Wistar rats
      were rendered myocardial infarction by ISO (150 mg kg(-1), once a day for two
      days). The concentrations of thiobarbituric acid reactive substances and lipid
      hydroperoxides were increased in hearts from ISO-treated rats, whereas the
      content of enzymic and nonenzymic antioxidants were declined in rats administered
      ISO. Oral pretreatment with SACS (40 mg kg(-1) and 80 mg kg(-1) daily for a
      period of 35 days) significantly (p < 0.05) decreased the lipid peroxidative
      products and significantly (p < 0.05) increased antioxidants in ISO-induced rats.
      Oral administration of SACS (40 mg kg(-1) and 80 mg kg(-1)) did not show any
      significant effect in normal rats. Thus, the present study shows that SACS
      exhibits antilipoperoxidative and antioxidant effects in experimental myocardial
      infarction.

PMID- 16906522
TI  - Influence of subacute treatment of some plant growth regulators on serum marker
      enzymes and erythrocyte and tissue antioxidant defense and lipid peroxidation in
      rats.
AB  - This study aims to investigate the effects of the plant growth regulators (PGRs)
      (2,3,5-triiodobenzoic acid (TIBA), Naphthaleneacetic acid (NAA), and 2,4
      dichlorofenoxyacetic acid (2,4-D)) on serum marker enzymes (aspartate
      aminotransferase (AST), alanin aminotransferase (ALT), creatine phosphokinase
      (CPK), and lactate dehydrogenase (LDH)), antioxidant defense systems (reduced
      glutathione (GSH), glutathione reductase (GR), superoxide dismutase (SOD),
      glutathione-S-transferase (GST), and catalase (CAT)), and lipid peroxidation
      content (malondialdehyde = MDA) in various tissues of rats. 50 and 100 ppm of
      PGRs as drinking water were administered orally to rats (Sprague-Dawley albino)
      ad libitum for 25 days continuously. The PGRs treatment caused different effects
      on the serum marker enzymes, antioxidant defense systems, and the MDA content in
      experimented rats compared to controls. Results showed that TIBA caused a
      significant decrease in serum AST activity with both the dosage whereas serum CPK
      was significantly increased with 100 ppm dosage of TIBA. Meanwhile, serum AST,
      CPK, and LDH activities were significantly increased with both dosage of NAA and
      2,4-D. The lipid peroxidation end-product MDA significantly increased in the all
      tissues treated with both dosages of PGRs without any change in the brain and
      erythrocyte of rats treated with both the dosages of 2,4-D. The GSH depletion in
      the kidney and brain tissues of rats treated with both dosages of PGRs was found
      to be significant. Furthermore, the GSH depletion in the erythrocyte of rats
      treated with both dosages of PGRs except 50 ppm dosage of 2,4-D was significant
      too. Also, the GSH level in the liver was significantly depleted with 50 ppm of
      2,4-D and NAA, whereas the GSH depletion in the same tissue did not significantly
      change with the treatment. The activity of antioxidant enzymes was also seriously
      affected by PGRs; SOD significantly decreased in the liver, heart, kidney, and
      brain of rats treated with both dosages of NAA, whereas the SOD activity in the
      erythrocytes, liver, and heart was either significantly decreased or not changed
      with two doses of 2,4-D and TIBA. Although the CAT activity significantly
      increased in the erythrocyte and brain of rats treated with both doses of PGRs,
      it was not changed in the liver, heart, and kidney. Meanwhile, the ancillary
      enzyme GR activity significantly increased in the brain, heart, and liver but
      decreased in the erythrocyte and kidney of rats treated with both doses of PGRs.
      The drug-metabolizing enzyme GST activity significantly increased in the heart
      and kidney but decreased in the brain and erythrocytes of rats treated with both
      dosages of PGRs. As a conclusion, the results indicate that PGRs might affect
      antioxidant potential enzymes, the activity of hepatic damage enzymes, and lipid
      peroxidation dose independently. Also, the rats resisted to oxidative stress via
      antioxidant mechanism but the antioxidant mechanism could not prevent the
      increases in lipid peroxidation in rat's tissues. These data, along with the
      determined changes, suggest that PGRs produced substantial systemic organ
      toxicity in the erythrocyte, liver, brain, heart, and kidney during the period of
      a 25-day subacute exposure.

PMID- 16906523
TI  - Modulation by ellagic acid of DCA-induced developmental toxicity in the zebrafish
      (Danio rerio).
AB  - The ability of ellagic acid (EA) to modulate dichloroacetic acid (DCA)-induced
      developmental toxicity and oxidative damage was examined in zebrafish embryos.
      Embryos were exposed to 20 mM EA administered concomitantly with 32 mM DCA at 4
      hours postfertilization (hpf) and 20 h later. Embryos were observed through 144
      hpf for developmental malformations, and production of superoxide anion (SA) and
      nitric oxide (NO) was determined in embryonic homogenates. DCA was shown to
      produce developmental abnormalities and significant levels of SA and NO in
      zebrafish embryos. EA exposure alleviated the developmental malformations
      observed in treated embryos and decreased the levels of SA and NO in those same
      embryos. Less than 10% of DCA + EA exposed embryos showed developmental
      malformations compared to 100% of embryos treated with DCA alone. Animals in this
      group that developed malformations were shown to have fewer defects than those
      treated with DCA only. Taken together, the results confirm the involvement of
      oxidative stress in the developmental toxicity of DCA in zebrafish embryos, and
      suggest possible protection against those effects with the use of antioxidants.

PMID- 16906524
TI  - Preventive effect of naringin on lipids, lipoproteins and lipid metabolic enzymes
      in isoproterenol-induced myocardial infarction in Wistar rats.
AB  - This study was designed to evaluate the preventive effect of naringin in
      isoproterenol (ISO)-induced myocardial infarction (MI) in rats. Rats were
      pretreated with naringin (10, 20, and 40 mg/kg body weight) orally for a period
      of 56 days. After the treatment period, ISO (85 mg/kg body weight) was
      administered subcutaneously to rats at an interval of 24 h for 2 days. There was
      a significant increase in the levels of total, ester, and free cholesterol,
      triglycerides (TG), and free fatty acids (FFA) in serum and heart and decrease in
      heart phospholipids (PL) in ISO-induced rats. Altered levels of lipoproteins and
      activities of 3-hydroxy-3-methylglutaryl-Coenzyme reductase A in liver and heart,
      lecithin cholesterol acyl transferase and lipoprotein lipase in plasma were also
      observed in ISO-induced rats. Pretreatment with naringin (10, 20, and 40 mg/kg)
      for a period of 56 days significantly decreased the levels of total, ester, and
      free cholesterol, TG, FFA in serum and heart and increased PL in heart. It also
      minimized the alterations in serum lipoproteins and lipid metabolic enzymes in
      ISO-induced rats. Thus, naringin has a lipid-lowering effect in ISO-induced MI
      rats.

PMID- 16906525
TI  - Aluminum toxicity elicits a dysfunctional TCA cycle and succinate accumulation in
      hepatocytes.
AB  - Aluminum (Al), a known environmental toxicant, has been linked to a variety of
      pathological conditions such as dialysis dementia, osteomalacia, Alzheimer's
      disease, and Parkinson's disease. However, its precise role in the pathogenesis
      of these disorders is not fully understood. Using hepatocytes as a model system,
      we have probed the impact of this trivalent metal on the aerobic energy
      generating machinery. Here we show that Al-exposed hepatocytes were characterized
      by lipid and protein oxidation and a dysfunctional tricarboxylic acid (TCA)
      cycle. BN-PAGE, SDS-PAGE, and Western blot analyses revealed a marked decrease in
      activity and expression of succinate dehydrogenase (SDH), alpha-ketoglutarate
      dehydrogenase (KGDH), isocitrate dehydrogenase-NAD+ (IDH), fumarase (FUM),
      aconitase (ACN), and cytochrome c oxidase (Cyt C Ox). 13C-NMR and HPLC studies
      further confirmed the disparate metabolism operative in control and Al-stressed
      cells and provided evidence for the accumulation of succinate in the latter
      cultures. In conclusion, these results suggest that Al toxicity promotes a
      dysfunctional TCA cycle and impedes ATP production, events that may contribute to
      various Al-induced abnormalities.

PMID- 16906526
TI  - Characterization of emulsified chitosan-PLGA matrices formed using controlled
      rate freezing and lyophilization technique.
AB  - This study evaluated the formation of chitosan-50:50 poly-lactic-co-glycolic acid
      (PLGA) blend matrices using controlled-rate freezing and lyophilization technique
      (CRFLT). An emulsion system was used in the presence of 1,2-dimyristoyl-sn
      glycero-3-phosphocholine (DMPC), a cellular component, as a stabilizer. Blended
      scaffolds showed an open pore morphology and homogenous interdispersion of PLGA
      and chitosan. Forming emulsions after dissolving PLGA in chloroform, benzene, or
      methylene chloride indicated better emulsion stability with benzene and
      chloroform. Scaffolds formed by freezing at -20, -78, and -196 degrees C from
      these emulsions showed significant influence of the solvent and freezing
      temperature on the microarchitecture of the scaffold. By controlling the
      concentration of chitosan, scaffolds with greater than 90% porosity were
      attained. Since the two polymers degrade by different mechanisms, formed
      scaffolds were analyzed for degradation characteristics for 4 weeks in presence
      of 10 mg/L lysozyme. These results showed no significant difference in the weight
      loss and dimension changes, as all scaffolds showed significant (a) weight loss
      and (b) nearly 60% reduction in volume. Further, pH of the incubation media
      decreased in all the samples. When cellular activity of green fluorescence
      protein-transfected smooth muscle cells was analyzed, no apparent cytotoxicity
      was observed. However, the cell spreading area decreased. In summary, these
      results show promising potential in tissue engineering and drug delivery
      applications.

PMID- 16906529
TI  - Tol2 transposon-mediated transgenesis in Xenopus tropicalis.
AB  - The diploid frog Xenopus tropicalis is becoming a powerful developmental genetic
      model system. Sequencing of the X. tropicalis genome is nearing completion and
      several labs are embarking on mutagenesis screens. We are interested in
      developing insertional mutagenesis strategies in X. tropicalis. Transposon
      mediated insertional mutagenesis, once used exclusively in plants and
      invertebrate systems, is now more widely applicable to vertebrates. The first
      step in developing transposons as tools for mutagenesis is to demonstrate that
      these mobile elements function efficiently in the target organism. Here, we show
      that the Medaka fish transposon, Tol2, is able to stably integrate into the X.
      tropicalis genome and will serve as a powerful tool for insertional mutagenesis
      strategies in the frog.

PMID- 16906530
TI  - Episodic memory--from brain to mind.
AB  - Neuronal mechanisms of episodic memory, the conscious recollection of
      autobiographical events, are largely unknown because electrophysiological studies
      in humans are conducted only in exceptional circumstances. Unit recording studies
      in animals are thus crucial for understanding the neurophysiological substrate
      that enables people to remember their individual past. Two features of episodic
      memory--autonoetic consciousness, the self-aware ability to "travel through
      time", and one-trial learning, the acquisition of information in one occurrence
      of the event--raise important questions about the validity of animal models and
      the ability of unit recording studies to capture essential aspects of memory for
      episodes. We argue that autonoetic experience is a feature of human consciousness
      rather than an obligatory aspect of memory for episodes, and that episodic memory
      is reconstructive and thus its key features can be modeled in animal behavioral
      tasks that do not involve either autonoetic consciousness or one-trial learning.
      We propose that the most powerful strategy for investigating neurophysiological
      mechanisms of episodic memory entails recording unit activity in brain areas
      homologous to those required for episodic memory in humans (e.g., hippocampus and
      prefrontal cortex) as animals perform tasks with explicitly defined episodic-like
      aspects. Within this framework, empirical data suggest that the basic structure
      of episodic memory is a temporally extended representation that distinguishes the
      beginning from the end of an event. Future research is needed to fully understand
      how neural encodings of context, sequences of items/events, and goals are
      integrated within mnemonic representations of autobiographical events.

PMID- 16906531
TI  - The IgD CH1 region contains the binding site for the human respiratory pathogen
      Moraxella catarrhalis IgD-binding protein MID.
AB  - The Moraxella catarrhalis IgD-binding protein (MID) has a unique specificity for
      human IgD, and the sequence with maximal IgD binding is located within the amino
      acids MID962-1200. In the present paper, we examined the MID binding site on IgD
      using a series of recombinant Ig. Full-length IgD, IgD F(ab')2, and an IgD F(ab')
      C290R mutant lacking the inter-heavy-chain cysteine 290 were manufactured.
      Furthermore, a series of IgD/IgG chimeras were constructed. ELISA, dot blot and
      flow cytometry were used to study the binding of purified Ig to native MID,
      recombinant MID962-1200 or to Moraxella with or without MID. MID962-1200 bound
      both the IgD F(ab')2 and F(ab') C290R, indicating that the binding occurred
      independently of antibody structure. When amino acids 157-224 of the IgD CH1
      region were substituted with IgG sequences, binding by M. catarrhalis or
      recombinant MID962-1200 was abolished. Subsequent smaller substitutions of IgD
      CH1 157-224 with IgG sequences led us to conclude that IgD CH1 amino acids 198
      206 were crucial for the interaction between MID and IgD.

PMID- 16906533
TI  - Evidence of NK cell dysfunction in SIV-infected rhesus monkeys: impairment of
      cytokine secretion and NKG2C/C2 expression.
AB  - Defects in the adaptive immune response have been extensively characterized in
      human immunodeficiency virus type-1 (HIV-1)-infected individuals; however, much
      less is known about the function of natural killer (NK) cells during the course
      of HIV-1 infection. In the present study, we demonstrate that the NK cells from
      simian immunodeficiency virus (SIV)-infected rhesus monkeys are significantly
      impaired in their ability to secrete IFN-gamma, TNF-alpha, and IL-2, while NK
      cell function in SIV-infected long-term non-progressor monkeys is similar to that
      of normal monkeys. These findings suggest that abnormal NK cell activity may
      contribute to the global immune dysfunction observed in HIV-1-infected
      individuals. NK cell function is modulated by several families of cell surface
      receptors, including the CD94/NKG2 family. We evaluated the messenger RNA levels
      of these inhibitory and activating NKG2 molecules in SIV-infected rhesus monkeys.
      These experiments demonstrate that the activating molecules NKG2C and NKG2C2 are
      significantly down-regulated in peripheral blood mononuclear cells of SIV
      infected rhesus monkeys, suggesting that the dysregulation of these molecules may
      contribute to the abnormal NK cell function observed in the setting of infection.

PMID- 16906532
TI  - Hierarchy of eosinophil chemoattractants: role of p38 mitogen-activated protein
      kinase.
AB  - Several chemoattractants can regulate the recruitment of eosinophils to sites of
      inflammation, but the hierarchy among them is unknown. We observed here that
      eosinophil chemotaxis towards eotaxin or 5-oxo-6,8,11,14-eicosatetraenoic acid (5
      oxo-ETE) was amplified up to sixfold in the presence of prostaglandin (PG) D2.
      This effect was only seen in eosinophils, and not in neutrophils or basophils.
      Pretreatment with the chemoattractant receptor-homologous molecule expressed on
      TH2 cells (CRTH2) antagonist ramatroban prevented the PGD2 enhancement of
      eosinophil migrations. In contrast, eotaxin or 5-oxo-ETE inhibited the migration
      of eosinophils towards PGD2. 5-oxo-ETE enhanced the chemotaxis to eotaxin, while
      eotaxin had no effect on 5-oxo-ETE-induced migration. 5-oxo-ETE induced the
      phosphorylation of p38 mitogen-activated protein kinase, and inhibition of p38
      mitogen-activated protein kinase by SB-202190 converted the effect of 5-oxo-ETE
      on the chemotaxis to PGD2 from inhibition to enhancement. The presence of blood
      or plasma markedly decreased the sensitivity of eosinophils to eotaxin or 5-oxo
      ETE, while responses to PGD2 were unaltered. In conclusion, PGD2 might be an
      initial chemoattractant, since it maintains its potency in the circulation and
      augments the responsiveness of eosinophils to other chemoattractants. In
      contrast, eotaxin seems to be an end-point chemoattractant, since it has reduced
      efficacy in blood and is capable of down-modulating eosinophil responsiveness to
      other chemoattractants.

PMID- 16906534
TI  - Antibody-independent B cell-intrinsic and -extrinsic roles for CD21/35.
AB  - Mice lacking C3, C4 or complement receptor 1/2 (Cr) have defective germinal
      centers (GC). The requirement for C4 implicates complement fixation by immune
      complexes (IC) via the classical pathway. Yet, transgenic (Tg) mice that lack
      circulating antibody but still express membrane IgM (mIgM) have normal GC
      responses. We showed previously that cross-linking mIgM leads to the deposition
      of C3 on the B cell surface and that disruption of this pathway diminishes GC
      responses. Here, we investigate the role of Cr in this process by generating mIgM
      Tg mice that lack Cr and serum Ig. These mIgM/Cr-/- mice have smaller, transient
      GC, with incomplete B cell receptor down-regulation and peanut agglutinin up
      regulation, compared to mIgM/Crwt counterparts. BM chimera experiments showed
      that Cr on B cells is required for normal GC responses. These results establish
      that Cr ligands generated at the B cell surface are sufficient for normal GC
      responses and function by signaling Cr on B cells. Unexpectedly, chimera
      experiments also showed a critical role for Cr on follicular dendritic cells
      (FDC), even in the absence of IC, indicating novel functions for FDC-expressed Cr
      beyond the capture of C3-coated IC.

PMID- 16906535
TI  - Development of nephritis but not sialadenitis in autoimmune-prone BAFF transgenic
      mice lacking marginal zone B cells.
AB  - B cell-activating factor belonging to the TNF family (BAFF) is a B cell survival
      factor required for B cell maturation. BAFF transgenic (Tg) mice develop
      autoimmune disorders characterized by autoantibody production, which leads to
      nephritis and salivary gland destruction (sialadenitis), features reminiscent of
      systemic lupus erythematosus and Sjogren's syndrome (SS), respectively. Disease
      in BAFF Tg mice correlates with the expansion of the marginal zone (MZ) B cell
      compartment and the abnormal presence of MZ-like B cells in the blood, LN and
      inflamed salivary glands, suggesting a role for these cells in BAFF-induced
      autoimmunity. Lymphotoxin-beta (LTbeta)-deficient mice show disrupted splenic
      architecture, lack MZ B cells and some peripheral LN, and are unable to mount T
      cell-dependent immune responses. BAFF Tg mice lacking LTbeta (LTbetaDelta-BTg)
      retained these defects, yet still developed nephritis associated with the
      presence of B-1 B cells in the kidneys. However, in contrast to old BAFF Tg mice,
      aging LTbetaDelta-BTg mice no longer developed sialadenitis. Thus, autoimmune
      disorders in BAFF Tg mice are possibly events coordinated by MZ and B-1 B cells
      at separate anatomical sites.

PMID- 16906537
TI  - The Helena syndromes.
AB  - The author gives a personal account on how he was introduced to the field of
      clinical genetics as a student of John Opitz in Helena, MT. That process was
      facilitated by the study of several malformation syndromes. Particularly
      instructive were the approaches to the cardio-facio-cutaneous, the Perlman, and
      the FG syndrome. These three conditions are briefly revisited with a critical
      perspective, made possible by the elapse of 20 years, since the time when the
      author became acquainted with them.

PMID- 16906536
TI  - Is there a higher incidence of maternal uniparental disomy 14 [upd(14)mat]?
      Detection of 10 new patients by methylation-specific PCR.
AB  - Maternal uniparental disomy for chromosome 14 [upd(14)mat] is associated with a
      characteristic phenotype including pre- and postnatal growth retardation,
      muscular hypotonia, feeding problems, motor delay, small hands and feet,
      precocious puberty and truncal obesity. Patients with upd(14)mat show features
      overlapping with Prader-Willi syndrome (PWS) and are probably underdiagnosed.
      Maternal upd(14) is frequently described in carriers of a Robertsonian
      translocation involving chromosome 14, but is also found in patients with a
      normal karyotype. Based on the above mentioned criteria we have identified six
      patients with upd(14)mat including two patients with a normal karyotype, one
      patient with a de novo Robertsonian translocation (14;21), one patient with a
      familial Robertsonian translocation (13;14) and two patients with a marker
      chromosome. In addition, we analyzed a cohort of 33 patients with low birth
      weight, feeding difficulties and consecutive obesity in whom PWS had been
      excluded by methylation analysis of SNRPN. In four of these patients (12%) we
      detected upd(14)mat. For rapid testing of upd(14)mat we analyzed the methylation
      status of the imprinted MEG3 locus. In conclusion, we recommend considering
      upd(14)mat in patients with low birth weight, growth retardation, neonatal
      feeding problems, muscular hypotonia, motor delay, precocious puberty and truncal
      obesity as well as in patients with a PWS like phenotype presenting with low
      birth weight, feeding difficulties and obesity.

PMID- 16906538
TI  - DHCR7 mutation carrier rates and prevalence of the RSH/Smith-Lemli-Opitz
      syndrome: where are the patients?
AB  - RSH/Smith-Lemli-Opitz (SLOS) is an inborn error of metabolism with protean
      manifestations. Its exact incidence and prevalence are not known; however, the
      carrier rate for the most frequently occurring mutation, the null mutation IVS8
      1G > C, is approximately 1 in 100 for the Caucasian population in North America
      (1%) and possibly as high as 1 in 50 to 1 in 30 in Central European populations
      (2-3.3%). Based on the allele frequencies and the proportion of this mutation
      observed in various patient populations, the expected incidence of RSH/SLOS in
      those populations was calculated and reported to be between 1 in 1,590 and 1 in
      17,000. However, around the world the observed prevalence and incidence are much
      lower than those calculated from the individual mutation carrier rates observed
      in any given population. The discrepancy between the expected incidence and
      prevalence can be explained only in part by the neonatal and infancy deaths of
      the most severely affected children with RSH/SLOS and the under ascertainment of
      mild and atypical cases at the mild end of the spectrum. RSH/SLOS may be
      responsible for a high number of miscarriages. Recent observations estimate the
      prevalence of SLOS at 16 weeks of gestation as similar to that observed at birth
      (approximately 1 in 60,000) suggesting that either reduced fertility of carrier
      couples or losses of affected embryos or fetuses in the first trimester play a
      significant role in reducing the second trimester prevalence of RSH/SLOS. It is
      possible that the estimates of carrier rates based on population screening for
      the most commonly occurring mutations may not reflect the true carrier rates in
      the population. In order to reconcile the above-mentioned paradoxes, we propose a
      model based on a higher than observed carrier frequency of the most common
      mutation and on very high fetal loss of homozygotes for that mutation.

PMID- 16906540
TI  - Steroids and glial cell function.
AB  - Hormonal and locally produced steroids act in the nervous system as
      neuroendocrine regulators, as trophic factors and as neuromodulators and have a
      major impact on neural development and function. Glial cells play a prominent
      role in the local production of steroids and in the mediation of steroid effects
      on neurons and other glial cells. In this review, we examine the role of glia in
      the synthesis and metabolism of steroids and the functional implications of glial
      steroidogenesis. We analyze the mechanisms of steroid signaling on glia,
      including the role of nuclear receptors and the mechanisms of membrane and
      cytoplasmic signaling mediated by changes in intracellular calcium levels and
      activation of signaling kinases. Effects of steroids on functional parameters of
      glia, such as proliferation, myelin formation, metabolism, cytoskeletal
      reorganization, and gliosis are also reviewed, as well as the implications of
      steroid actions on glia for the regulation of synaptic function and connectivity,
      the regulation of neuroendocrine events, and the response of neural tissue to
      injury.

PMID- 16906539
TI  - Linking Antley-Bixler syndrome and congenital adrenal hyperplasia: a novel case
      of P450 oxidoreductase deficiency.
AB  - The Antley-Bixler syndrome (ABS) is a multiple congenital malformation syndrome
      with craniosynostosis, radiohumeral synostosis, femoral bowing, choanal atresia
      or stenosis, joint contractures, urogenital abnormalities and, often, early
      death. Autosomal recessive and dominant inheritance have been postulated, as has
      fluconazole teratogenesis. Mutations in POR (P450 (cytochrome) oxidoreductase, an
      essential electron donor to enzymes participating in cholesterol biosynthesis),
      have been identified in some patients with the ABS phenotype. Recent evidence
      suggests that these mutations cause attenuated steroid hydroxylation, which in
      turn, causes congenital adrenal hyperplasia (CAH) with ambiguous genitalia in
      both sexes and glucocorticoid deficiency. Here, we report on a new patient with
      findings of both ABS and CAH that further illustrates how low maternal estriol at
      prenatal screening can serve as a marker steroid facilitating early diagnosis.

PMID- 16906541
TI  - Stimulation of TLR9 with CpG ODN enhances apoptosis of glioma and prolongs the
      survival of mice with experimental brain tumors.
AB  - Toll-like receptors (TLRs) recognize a set of conserved molecular structures, so
      called pathogen-associated molecular patterns, which allow them to sense and
      initiate innate and adaptive immune responses. In this study, we examined the
      expression of TLRs in both human and murine glioma. We then analyzed the change
      in TLR expression after treatment with synthetic phosphorothioate
      oligodeoxynucleotides (ODNs) containing unmethylated CpG dinucleotides (CpG
      ODNs), strong activators of both innate and adaptive immunity. In addition, we
      investigated the in vivo effect of CpG injection into C57BL/6 mice implanted with
      syngeneic GL261 glioma. Our results indicate that TLR9 is overexpressed in human
      and murine glioma cell lines and CpG stimulation prolongs the survival of mice
      with experimental brain tumors. CpGs induce TLR9 down-regulation, followed by
      apoptosis of GL261 cells in vitro as well as in vivo. Furthermore, the effects of
      CpG stimulation appear to enhance the antigen presenting capacity of microglia,
      shift the immune response toward CD8(+) T cells, and decrease the number of
      CD4(+)CD25(+) regulatory T cells. Taken together, our data support the role of
      CpG in glioma immunotherapy and provide a rationale for further clinical
      development of CpG therapy in patients with malignant glioma.

PMID- 16906542
TI  - Glial cell line-derived neurotrophic factor promotes olfactory ensheathing cells
      migration.
AB  - Olfactory ensheathing cells (OECs) are a unique type of macroglia with axonal
      growth-promoting properties. The migrating ability of OECs in CNS is essential
      for neural regeneration. However, little is known about the extracellular and
      intracellular factors that regulate OEC migration. In the present study, we
      examined the effects of glial cell line-derived neurotrophic factor (GDNF) on
      OECs migration. Initially, the "scratch" migration assay, Boyden chamber assay,
      and explant migration assay showed that GDNF could promote OECs migration in
      vitro. Treatment of OECs with GDNF also induced cytoskeleton reorganization and
      up-regulated expression of cytoskeleton proteins. GDNF-induced OECs migration was
      demonstrated depending on GFRalpha-1 and Ret receptor, and activation of JNK and
      Src signaling cascades. Furthermore, GDNF was found to promote implanted OECs
      migration in a spinal cord hemisection injury model. Together, we report, to our
      knowledge for the first time, that GDNF stimulate OECs migration in vitro and in
      vivo.

PMID- 16906543
TI  - Examination of cellular and molecular events associated with optic nerve axotomy.
AB  - PURPOSE: Analyzing cellular behavior during scar formation and determining the
      expression of growth inhibiting molecules in the optic nerve and retina following
      acute optic nerve injury. METHODS: A rat model of complete transection of the
      optic nerve that spares the vascular supply and the neural scaffold was used. The
      response of the optic nerve and retinas to axotomy was studied by immunological
      and biochemical approaches. RESULTS: Optic nerve axotomy led to massive cell
      invasion at the site of injury that spread along both sides of the nerve. The
      cells were microglia, oligodendrocytes, and to a lesser extent astrocytes. A
      marked induction of semaphorin 3A was evident, especially in the area of the
      scar, and persisted up to the 28th day of the experiment. Expression of
      neuropilin-1, a component of the semaphorin 3A receptor, increased following
      injury. The molecular events associated with axotomy were studied by measuring
      the levels of semaphorin 3A, p38 MAPK, and ERK1/2 in the retina. Semaphorin 3A
      levels and the activated form of p38 were elevated 3 days post-axotomy and then
      declined; ERK1/2 activation levels reached their peak 14 days post axotomy. Acute
      nerve injury led to morphological alterations in oligodendrocytes, astrocytes,
      and the extracellular matrix, disrupting the delicate internal organization of
      the optic nerve. CONCLUSIONS: We suggest that cell invasion, semaphorin 3A and
      neuropilin-1 induction, and disruption of the internal organization of the optic
      nerve contribute to axotomy-induced degenerative processes.

PMID- 16906544
TI  - Interactions between mouse IgG2 antibodies are common and mediated by plasma C1q.
AB  - BACKGROUND: The simultaneous use of multiple antibodies for multicolor flow
      cytometry is increasingly common and presents the opportunity for antibody
      interactions. METHODS: Antibodies of differing isotypes were evaluated in pair
      wise combinations for the presence of antibody interactions, using a standard
      whole blood lysing method or variations thereof. RESULTS: Artifactual
      interactions were identified and preferentially involved IgG2a (58%) or IgG2b
      (33%) antibodies and a single IgG1 antibody (3%). The interactions were present
      in all 10 random peripheral blood samples evaluated and required only whole blood
      and the two antibodies. Plasma removal prior to antibody incubation eliminated
      the interaction, as did switching any single IgG2 antibody to an IgG1 clone. Heat
      inactivated plasma eliminated the interactions, and the addition of purified C1q
      to washed cells was capable of recreating the interaction in its entirety,
      confirming the mediation by complement C1q. CONCLUSIONS: Complement C1q mediates
      significant interactions between mouse IgG2 class antibodies; these interactions
      are very common and may be prevented by either complete serum removal or use of
      alternate IgG1 clones. Such interactions represent a significant potential source
      of artifact in the use of whole blood lysis methods for specimen preparation for
      multicolor flow cytometry.

PMID- 16906545
TI  - Low cost CD4 enumeration using generic monoclonal antibody reagents and a two
      color user-defined MultiSET protocol.
AB  - BACKGROUND: The standard three-tube, three-color flow cytometric method utilizing
      the TriTEST reagents in conjunction with the MultiSET software commonly used in
      most laboratories in Thailand for CD4 enumeration is expensive and thus
      unavailable to most HIV-infected patients. A more affordable method, i.e., the
      PanLeucogating protocol using only two monoclonal antibody reagents, has been
      described but requires the use of the CellQUEST software that does not have
      automatic gating and reporting facilities. We describe a simple protocol that
      utilizes a two-color user-defined protocol with the automated MultiSET software
      for the acquisition, analysis, and reporting of CD4 results. METHODS: A two-color
      user-defined protocol was set up following instructions in the Becton Dickinson
      Biosciences MultiSET manual, adhering strictly to the information regarding the
      Gate and Attractor Hierarchy for analyzing various reagent combinations. This
      simple two-color user-defined MultiSET software was evaluated using generic
      monoclonal reagents in comparison with the standard TriTEST/MultiSET protocol.
      RESULTS: The two-color user-defined MultiSET software is easy to use. It requires
      only modification of the original MultiSET program and the results obtained are
      comparable with those derived from the standard TriTEST/MultiSET protocol.
      CONCLUSION: The use of this easy and reliable two-color user-defined MultiSET
      protocol represents an affordable alternative to CD4 testing in resource-poor
      settings.

PMID- 16906546
TI  - Single platform enumeration of lymphocyte subsets in healthy Indians aged between
      18 and 49 years.

PMID- 16906547
TI  - Growing the coronary tree: the quail saga.

PMID- 16906548
TI  - Atrioventricular block and wiry hair in Teebi hypertelorism syndrome.
AB  - We report on a 4 1/2-year-old girl with clinical features of Teebi hypertelorism
      syndrome (THS), including a prominent forehead with a widow's peak, heavy and
      broad eyebrows, hypertelorism, long palpebral fissures, ptosis, a thin upper lip,
      a grooved chin, and a left preauricular cyst. She required a pacemaker for third
      degree atrioventricular (AV) block, a finding that has not been previously
      reported in 36 other patients with THS and for which we were unable to identify
      other causes. We have reviewed the previous reports of THS and note a
      characteristic facial appearance with hypertelorism, heavy, broad, and arched
      eyebrows, a thin upper lip with a long and deep philtrum, and a prominent
      forehead. Structural cardiac defects were present in five patients, implying that
      cardiac investigations are warranted in patients with a cardiac murmur and a
      clinical diagnosis of THS.

PMID- 16906549
TI  - Impact of neurofibromatosis 1 on Quality of Life: a cross-sectional study of 176
      American cases.
AB  - Neurofibromatosis 1 (NF1), a genetic condition most commonly characterized by the
      presence of dermal neurofibromas and cafe au lait macules, has a significant
      impact on Quality of Life (QoL). There is a wide range of phenotypic variability,
      so that affected individuals may have either medically devastating or relatively
      mild manifestations that do not impact their daily lives. In this study, the SF
      36 and Skindex questionnaires were used to quantitatively investigate the impact
      of severity and visibility on QoL in an American population. Participants were
      recruited primarily through advertisements distributed by The Children's Tumor
      Foundation (CTF). The majority participated by completing a mailed questionnaire
      in which they rated themselves using Ablon's visibility and Riccardi's severity
      scales, and then completed the SF-36 and Skindex questionnaires. Participants
      with NF1 reported a significant impact in all aspects of skin-disease-specific
      QoL, but the emotional aspect demonstrated the greatest effect. Participants with
      more visible signs of NF1 reported significantly greater overall effects on their
      skin-disease-specific QoL than those whose manifestations were more subtle. All
      domains of general health QoL were affected as well, especially in participants
      who reported having severe complications. Interestingly, greater visibility was
      not found to be associated with a significant decrease in general health QoL.
      These findings are consistent with those found in a French cohort, and
      demonstrate the utility of incorporating tools designed for use in both the
      general population and for patients with skin disease in examining the impact of
      NF1 on QoL.

PMID- 16906550
TI  - Array comparative genomic hybridization analysis in first-trimester spontaneous
      abortions with 'normal' karyotypes.
AB  - Array comparative genomic hybridization (array CGH) analysis was conducted in
      chorionic villous samples from 20 first-trimester spontaneous abortions with G
      banding normal chromosomes. A microarray, containing 2,173 BAC clones and
      covering the whole genome with a 1.5-Mb resolution, was constructed and used in
      the analysis. Two deletions were identified: a 1.4-Mb deletion at 3p26.2-p26.3
      and a 13.7-Mb deletion at 13q32.3-qter. Reexamination of chromosome preparations
      from the sample with the 13.7-Mb deletion documented a mixture of cells with the
      13q- chromosome and those with 46,XX chromosomes, the latter of which are likely
      to have been derived from contaminating decidual cells. This left the 1.4-Mb 3p
      deletion as the only instance with submicroscopic imbalance detected, giving a
      frequency of 1 in 19 (5%) G-banding normal abortions.

PMID- 16906551
TI  - A non-obese boy with Prader-Willi syndrome shows cardiopulmonary impairment due
      to severe kyphoscoliosis.

PMID- 16906552
TI  - Trying to be precise about vagueness.
AB  - A previous investigation by Lambert et al., which used computer simulation to
      examine the influence of choice of prior distribution on inferences from Bayesian
      random effects meta-analysis, is critically examined from a number of viewpoints.
      The practical example used is shown to be problematic. The various prior
      distributions are shown to be unreasonable in terms of what they imply about the
      joint distribution of the overall treatment effect and the random effects
      variance. An alternative form of prior distribution is tentatively proposed.
      Finally, some practical recommendations are made that stress the value both of
      fixed effect analyses and of frequentist approaches as well as various diagnostic
      investigations.

PMID- 16906553
TI  - Issues in the use of adaptive clinical trial designs.
AB  - Sequential sampling plans are often used in the monitoring of clinical trials in
      order to address the ethical and efficiency issues inherent in human testing of a
      new treatment or preventive agent for disease. Group sequential stopping rules
      are perhaps the most commonly used approaches, but in recent years, a number of
      authors have proposed adaptive methods of choosing a stopping rule. In general,
      such adaptive approaches come at a price of inefficiency (almost always) and
      clouding of the scientific question (sometimes). In this paper, I review the
      degree of adaptation possible within the largely prespecified group sequential
      stopping rules, and discuss the operating characteristics that can be
      characterized fully prior to collection of the data. I then discuss the greater
      flexibility possible when using several of the adaptive approaches receiving the
      greatest attention in the statistical literature and conclude with a discussion
      of the scientific and statistical issues raised by their use.

PMID- 16906554
TI  - Flexible random-effects models using Bayesian semi-parametric models:
      applications to institutional comparisons.
AB  - Random effects models are used in many applications in medical statistics,
      including meta-analysis, cluster randomized trials and comparisons of health care
      providers. This paper provides a tutorial on the practical implementation of a
      flexible random effects model based on methodology developed in Bayesian non
      parametrics literature, and implemented in freely available software. The
      approach is applied to the problem of hospital comparisons using routine
      performance data, and among other benefits provides a diagnostic to detect
      clusters of providers with unusual results, thus avoiding problems caused by
      masking in traditional parametric approaches. By providing code for Winbugs we
      hope that the model can be used by applied statisticians working in a wide
      variety of applications.

PMID- 16906555
TI  - Dwarfism in the ancient Mediterranean world.

PMID- 16906556
TI  - Prevalence of Angelman syndrome and Prader-Willi syndrome in Estonian children:
      sister syndromes not equally represented.
AB  - In 2000-2004, we performed a focused search for individuals with Angelman
      syndrome (AS) and Prader-Willi syndrome (PWS) aiming to establish the prevalence
      data for the individuals born between 1984 and 2004 in Estonia. All persons with
      probable AS or PWS (n = 184) were studied using the DNA methylation test.
      Individuals with abnormal methylation were all further tested by chromosomal and
      FISH analysis, and if necessary for uniparental disomy and UBE3A gene mutation.
      Nineteen cases with abnormal methylation test result were identified. Seven of
      them had AS, including six (85.7%) due to 15q11-13 deletion and one paternal
      UPD15. Twelve subjects had PWS: 4 (33%) 15q11-13 deletions, 6 (50%) maternal
      UPD15, 1 unbalanced chromosome 14;15 translocation resulting in a chromosome
      15pter-q13 deletion, and 1 Robertsonian 15q;15q translocation. The minimum
      livebirth prevalence in 1984-2004 for AS was 1:52,181 (95% CI 1:25,326
      1:1,29,785) and for PWS 1:30,439 (95% CI 1:17,425-1:58,908). The livebirth
      prevalence of AS and PWS increased within this period, but the change was
      statistically significant only for PWS (P = 0.032), from expected 1:88,495 (95%
      CI 1:24,390-1:3,22,580) to expected 1:12,547 (95% CI 1:540-1:29,154). Six
      individuals with AS and 11 with PWS were alive on the prevalence day (January 1,
      2005), indicating the point prevalence proportion of 1:56,112 (95% CI 1:25,780
      1:1,52,899) and 1:30,606 (95% CI 1:17,105-1:61,311), respectively. Our results
      showing the birth prevalence of AS 1.7 times less than PWS challenge the opinion
      that both syndromes are equally represented, and are in line with the view that
      mutations in sperm and oocytes occur at different frequencies.

PMID- 16906557
TI  - Clinical experience with array CGH: case presentations from nine months of
      practice.
AB  - A total of 124 individuals were tested in the initial 9 months that array CGH
      technology was offered to clinical genetics patients. In 11 of these patients
      array CGH identified a previously unsuspected diagnosis. A suspected diagnosis
      was confirmed in three patients. A single case in this series proved to be a
      polymorphic copy number variant. This paper describes five of the patients with
      previously unsuspected diagnoses in detail. We suggest that array CGH is an
      improved tool ready for routine use in clinical genetics.

PMID- 16906558
TI  - Clinical phenotype and molecular characterization of 6q terminal deletion
      syndrome: Five new cases.
AB  - Mental retardation, facial dysmorphisms, seizures, and brain abnormalities are
      features of 6q terminal deletions. We have ascertained five patients with 6q
      subtelomere deletions (four de novo, one as a result of an unbalanced
      translocation) and determined the size of the deletion ranging from 3 to 13 Mb.
      Our patients showed a recognizable phenotype including mental retardation,
      characteristic facial appearance, and a distinctive clinico-neuroradiological
      picture. Focal epilepsy with consistent electroencephalographic features and with
      certain brain anomalies on neuroimaging studies should suggest 6q terminal
      deletion. The awareness of the distinctive clinical picture will help in the
      diagnosis of this chromosomal abnormality.

PMID- 16906559
TI  - A previously unreported mutation in a Currarino syndrome kindred.
AB  - Currarino syndrome consists of autosomal dominant hereditary sacral dysgenesis
      that is caused by mutations of the HOX gene, HLXB9. Sacral malformation,
      presacral mass, and anorectal malformations comprise the classic triad, but other
      common symptoms and malformations include neonatal-onset bowel obstruction,
      chronic constipation, recurrent perianal sepsis, renal/urinary tract anomalies,
      female internal genital anomalies, tethered spinal cord, and anterior
      meningocele. Up to 33% of patients are asymptomatic. There is marked inter- and
      intrafamilial variability in expression, and no genotype/phenotype correlations
      have been identified. To date, 32 different mutations have been identified in
      HLXB9: all nine missense mutations were found in the homeodomain, while the
      others were nonsense, frameshift, splice site mutations, or heterozygous whole
      gene deletions. We report a four-generation family with Currarino syndrome
      varying in severity from very mild to full expression of the Currarino triad.
      They were found to carry a previously unreported nonsense mutation, E283X, absent
      in tested asymptomatic first-degree relatives. This family provides additional
      information on the degree of intrafamilial variability associated with HLXB9
      mutations.

PMID- 16906560
TI  - Comprehensive genome and transcriptome analysis of the 11q13 amplicon in human
      oral cancer and synteny to the 7F5 amplicon in murine oral carcinoma.
AB  - 11q13 amplification occurs in a wide variety of tumors, including almost half of
      oral squamous cell carcinomas (OSCC) where it has been correlated with a poor
      outcome. In this study, we compiled 3.6 Mb of DNA sequence in the 11q13 amplicon
      core and refined the physical map of the amplicon. In the process, we determined
      the genomic structure and normal tissue expression patterns of two recently
      identified genes, TAOS2/TMEM16A and MRGF, which reside in the amplicon core. We
      then quantified DNA copy number and mRNA expression of all genes in the 11q13
      amplicon in cell lines and primary tumors from OSCC. With the exception of FGF3,
      FGF4, FGF19, and MRGF, all genes were overexpressed in most tumors with genomic
      amplification. Furthermore, we found that the expression of genes in the amplicon
      appeared to be highly coordinated, making it difficult to determine which gene or
      genes are driving amplification. However, in nonamplified primary tumors, three
      genes, TAOS2/TMEM16A, OCIM, and TPCN2, are frequently overexpressed, whereas
      CCND1 and EMS1 are not. These results suggest that in addition to CCND1 and EMS1,
      other important genes also may be target genes driving 11q13 amplification. We
      hypothesize that 11q13 amplification may be driven by a cassette of genes that
      provide growth or metastatic advantage to cancer cells. This is supported by the
      finding that the human 11q13 amplicon core is syntenic to mouse chromosomal band
      7F5, which is frequently amplified in chemically induced murine OSCC. This
      article contains Supplementary Material available at
      http://www.interscience.wiley.com/jpages/1045-2257/suppmat

PMID- 16906561
TI  - High cognitive functioning and behavioral phenotype in Pallister-Killian
      syndrome.
AB  - Pallister-Killian syndrome (PKS) is a rare syndrome of multiple congenital
      anomalies attributable to the presence of a mosaic supernumerary isochromosome
      12p. The syndrome presents with a recognizable pattern of findings including:
      pigmentary skin changes, characteristic facial features (sparse anterior scalp
      hair, flattened midface, macrostomia, and coarsening of the facial features), and
      developmental delay. The developmental phenotype of PKS is quite variable, but
      most are considered to fall into the profound range of developmental retardation.
      We report on an individual with classical features of PKS with development
      significantly better than that reported in the literature. Developmental and
      behavioral testing in this individual alters the range of developmental
      expectation in PKS, and highlights the need for consideration of chromosomal
      analysis in individuals with normal or near-normal intelligence if other physical
      phenotypic features of PKS are present.

PMID- 16906562
TI  - Tetralogy of Fallot with absent pulmonary valve in a de novo derivative
      chromosome 9 with duplication of 9p13 --> 9pter and deletion of 9q34.3.

PMID- 16906563
TI  - Risk of limb deficiency defects associated with NAT1, NAT2, GSTT1, GSTM1, and
      NOS3 genetic variants, maternal smoking, and vitamin supplement intake.
AB  - Increasing epidemiologic evidence suggests that genetic susceptibilities
      contribute to birth defects risks, especially in combination with other
      environmental exposures. This analysis examines the association of risk of limb
      deficiency defects with infant genotypes for N-acetyltranferases (NAT1, NAT2),
      glutathione-S-tranferases (GSTT1, GSTM1), and endothelial nitric oxide synthase
      (NOS3). The combined effects of infant genotype with maternal smoking and
      supplement intake were also examined. The authors genotyped 92 cases and 201 non
      malformed controls from a California population-based case-control study (1987
      1988 birth cohort). Several of the infant genotypes were associated with an at
      least 1.5-fold increased risk for limb deficiency defects: homozygosity for the
      NAT1 1088 and 1095 polymorphisms, heterozygosity and homozygosity for the NOS3 A(
      922)G polymorphism, and heterozygosity (but not homozygosity) for the NOS3 G894T
      polymorphism. The authors hypothesized that the effects of selected variant
      genotypes in the presence of maternal smoking, or in the absence of supplement
      intake, may exceed effects of any of these factors alone. A few observations
      suggested that risks were greatest among infants with variant genotypes, whose
      mothers also smoked or did not take supplements, but most did not, and risk
      estimates were imprecise. Further studies exploring genetic susceptibility and
      combined gene-environment effects with respect to limb development will be
      important to continued improvement of our understanding of the etiology of limb
      anomalies.

PMID- 16906564
TI  - Autism spectrum disorder in Fragile X syndrome: differential contribution of
      adaptive socialization and social withdrawal.
AB  - The present study extends our previous work on characterizing the profile of
      social behavior abnormalities in boys with Fragile X (FraX) and autism spectrum
      disorder (ASD) using clinically oriented behavioral rating scales and
      standardized instruments. The goal was to further distinguish behavioral
      parameters contributing to the diagnostic classification of FraX + ASD. The study
      design included two cohorts of boys with FraX (3-8 years), a larger main cohort
      for cross-sectional analyses (n = 56, 24 with ASD), and a longitudinal subset (n
      = 30, 11 with ASD) of the main cohort with up to 3 yearly observations. The focus
      was on the relative contribution of delayed adaptive socialization and social
      withdrawal, including item components of their corresponding rating instruments,
      to the diagnosis of ASD in boys with FraX. Using a combination of regression
      analyses, we demonstrated that: (1) as delayed socialization, social withdrawal
      is also a correlate of FraX + ASD; (2) items of social withdrawal scales
      representing avoidance were the main predictors of ASD status, particularly in
      older boys; (3) adaptive socialization skills reflecting rules of social behavior
      and recognition and labeling of emotions, linked to verbal reasoning abilities,
      were selectively associated with FraX + ASD; (4) adaptive socialization is the
      primary determinant over time of ASD status in boys with FraX; and (5) integrated
      adaptive socialization-social withdrawal models allow the identification of
      distinctive FraX + ASD subgroups. Altogether, our findings suggest that two
      distinct but interrelated social behavior abnormalities, one linked to impaired
      cognitive processes (delayed socialization) and the second one to disturbance in
      limbic circuits (avoidance), play a role in the development of ASD in boys with
      FraX.

PMID- 16906565
TI  - Expanding the clinical spectrum of MYCN-related Feingold syndrome.

PMID- 16906566
TI  - Cornelia de Lange syndrome: parental preferences regarding the provision of
      medical information.
AB  - We surveyed 57 caregivers of children with Cornelia de Lange syndrome (CdLS)
      using a self-report questionnaire designed to elicit their experiences with
      receiving information regarding health complications associated with this
      multisystem disorder. Their most frequent sources of information at the time of
      diagnosis were a health care provider (86%) and the CdLS Foundation (72%).
      Although most caregivers (82%) indicated a desire to receive information about
      all possible CdLS related health complications, on average they recalled
      receiving information on only 64% of their child's current or future health
      complications. For two of the top three complications (as ranked by caregivers),
      information was available to fewer than half of the caregivers at diagnosis. Only
      40% of caregivers were satisfied with the amount of information received at
      diagnosis, while only 45% felt that the information they received was useful.
      Caregivers indicated a preference for receiving information in written format
      (59%) or verbally (39%). Our results indicate that caregivers of children with
      CdLS report a high need for information at diagnosis, regarding their child's
      actual or potential health complications. Dissatisfaction may result both from a
      deficiency in information provided, as well as a mismatch between issues
      mentioned and those that caregivers deem most important. Caregivers may benefit
      maximally from receiving information in person at the time of diagnosis as well
      as having an additional written source of information. These findings highlight
      the importance of complementary sources of information for caregivers and are
      likely to be relevant for other multisystem disorders.

PMID- 16906567
TI  - Prenatal diagnosis of episodic tachypnea in an infant with OFD VI.
AB  - Episodic tachypnea is a typical neonatal presentation of Joubert syndrome, but
      may also occur in infants with other anomalies of the cerebellar vermis. Even
      though fetuses at risk for Joubert syndrome are usually closely followed by
      ultrasound, this respiratory pattern has only once been described prenatally. We
      describe a patient who presented prenatally with posterior meningocele, Dandy
      Walker cyst, and four limb polydactyly on ultrasound. Amniocentesis showed a
      normal male karyotype and normal 7DHC. At 31 weeks, episodic fetal tachypnea was
      noted on ultrasound. The working diagnosis was Joubert syndrome or oro-facio
      digital syndrome type VI (OFD VI). At birth, in addition to the findings noted
      prenatally, he had multiple nodules of his tongue, a Y-shaped metacarpal and
      micropenis. His respiratory pattern was notable for alternating tachypnea and
      apnea with respiratory rates up to 200 followed by apnea and bradycardia.
      Magnetic resonance image showed Dandy-Walker with massive 4th ventricle, complete
      absence of the cerebellar vermis, hypoplastic brainstem, and small meningocele.
      Development is profoundly delayed and he remains ventilator dependent. Both the
      previously described Joubert patient with prenatally recognized tachypnea, and
      our patient are atypical for Joubert syndrome since they have polydactyly (which
      occurs in only 8% of Joubert patients) and hamartomas of the tongue (which occur
      in 2%). Despite the tongue hamartomas, these patients are not entirely typical
      for OFD VI, since their polydactyly is postaxial. The observation of prenatal
      tachypnea in these two patients, but not in typical Joubert patients, suggests
      they have either a variant of OFD VI or a new Joubert or OFD-like syndrome.

PMID- 16906568
TI  - Maternal 21-hydroxylase deficiency and uniparental isodisomy of chromosome 6 and
      X results in a child with 21-hydroxylase deficiency and Klinefelter syndrome.

PMID- 16906569
TI  - Patched mutations and hairy skin patches: a new sign in Gorlin syndrome.
AB  - We report on the occurrence of discrete patches of unusually long pigmented hair
      on the skin of three patients with Gorlin syndrome from two unrelated families
      with confirmed heterozygous mutations in the Patched (PTCH) gene. The PTCH
      protein is a negative regulator of Hedgehog signaling, and the Sonic Hedgehog
      (SHH)-PTCH pathway is known to play an important role in the formation and
      cycling of the hair follicle. We believe that the patches represent a genuine
      physical sign associated with Gorlin syndrome, and discuss molecular mechanisms
      by which they might arise.

PMID- 16906570
TI  - Epiphyseal dysplasia and other skeletal anomalies in a patient with the 6p25
      microdeletion syndrome.
AB  - The 6p25 microdeletion syndrome comprises the Axenfeld-Rieger eye anomaly in
      association with a characteristic facies, developmental delay, hearing loss, and
      organ malformations. Skeletal anomalies in the form of hemivertebrae, clubfeet,
      and other positional joint anomalies have also been described in some patients.
      We report on a patient with a 2.2-2.4 Mb terminal microdeletion of the short arm
      of chromosome 6 who in addition had abnormalities of the proximal femoral and
      humeral epiphyses. We suggest that an epiphyseal dysplasia may be an additional
      clinical component of the 6p25 microdeletion syndrome.

PMID- 16906571
TI  - CD44 regulates myoblast migration and differentiation.
AB  - CD44 is a transmembrane protein that plays a role in cell-cell interactions and
      motility in a number of cell types. Cell-cell interactions are critical for
      myoblast differentiation and fusion but whether CD44 regulates myogenesis is
      unknown. Here, we show that CD44 plays a functional role in early myogenesis.
      Analyses of myofiber cross-sectional area, after local injury in mouse tibialis
      anterior (TA) muscles, revealed that growth was transiently delayed in the
      absence of CD44. A muscle-intrinsic role for CD44 is suggested as primary
      myoblasts from CD44(-/-) mice displayed attenuated differentiation and subsequent
      myotube formation at early times in a differentiation-inducing in vitro
      environment. Chemotaxis of CD44(-/-) myoblasts toward hepatocyte growth factor
      (HGF) and basic fibroblast growth factor (bFGF) was totally abrogated, although
      expression of their respective receptors did not appear to differ from wild-type.
      Furthermore, motility of CD44(-/-) myoblasts was decreased at early stages of
      differentiation as determined by time-lapse microscopy. Wild-type myoblasts
      contained two subpopulations of slow- and fast-migrating cells, whereas CD44(-/-)
      myoblasts were composed predominantly of the slower migrating subpopulation.
      Taken together, these data suggest that myoblast migration and differentiation
      are closely linked and CD44 is a key regulator.

PMID- 16906572
TI  - ZAP-70 expression is low in normal precursor B cells or hematogones.
AB  - BACKGROUND: Zeta-associated protein (ZAP-70) expression has been associated with
      a less favorable prognosis in chronic lymphocytic leukemia (CLL). The role of ZAP
      70 in immature B-cells is not well understood. Immature or precursor B
      lymphocytes (hematogones) often occur in clinical samples and coexpress CD10,
      CD38, and CD19 lacking surface immunoglobulin expression. The present study was
      carried out in an attempt to further elucidate the role of ZAP-70 in the spectrum
      of B-cells seen in clinical specimens. METHODS: ZAP-70 expression was evaluated
      on 25 patient samples that expressed greater than 2% of
      CD10(+)/CD38(bright)/CD19(+) coexpression during routine evaluation. In our
      sample set, the hematogone expression ranged from 2 to 18% of total leukocytes
      and occurred in a variety of conditions, including CLL, NHL, AML, MDS, Hodgkins
      Disease, and Multiple Myeloma. The method of ZAP-70 detection was that routinely
      applied to our clinical testing of CLL samples supplemented with the
      determination of ZAP-70 levels in the CD38(bright)/CD19(+) coexpressing cells.
      RESULTS: In all cases ZAP-70 was not expressed on the CD5 negative, CD38/CD19
      coexpressing precusor B cells. In all cases hematogones were found to not express
      significant levels of ZAP-70. CONCLUSION: The presence of hematogones in clinical
      samples should be recognized so as to not adversely influence prognostic studies
      of ZAP-70 or CD38 in CLL.

PMID- 16906573
TI  - ZAP-70 by flow cytometry: a comparison of different antibodies, anticoagulants,
      and methods of analysis.
AB  - BACKGROUND: The clinical course of chronic lymphocytic leukaemia (CLL) is
      variable. ZAP-70 expression is believed to provide prognostic information. The
      flow cytometric detection of ZAP-70 is difficult because it is an intracellular
      antigen with weak expression in CLL. Consensus has not been reached as to the
      best method for measurement. METHODS: We analyzed 72 CLL patient samples for ZAP
      70 expression and IgVH mutational status. Sensitivity and specificity of ZAP-70
      expression against IgVH mutational status were assessed for two clones (2F3.2 and
      1E7.2) and for four methods of analysis: percentage positivity (PP), comparing
      test to isotype control, ratio of geometric means of test and isotype control,
      and percentage and ratiometric methods comparing test and T/NK cell populations.
      The effects of anticoagulant, collection times, and time to analysis were also
      evaluated. RESULTS: Sensitivity and specificity were 85 and 88%, respectively,
      for Upstate PP; 70 and 88% for Caltag PP; 89 and 91% for Upstate ratio; 89 and
      88% for Caltag ratio. Intraobserver variability was smaller when ZAP-70
      expression was assessed using a ratiometric approach rather than the percentage
      method. By 48 h, we observed an average decrease of 13% in the Caltag ratio in
      the heparin preserved samples compared to an increase of 3% in those collected in
      EDTA. Within the first 24-h period, a greater percent variability was observed in
      those samples collected into EDTA compared with heparin. CONCLUSION: Our data
      support a rapid method for ZAP-70 measurement using commercially available
      fixation/permeabilization reagents, a conjugated antibody, and a ratiometric
      method of analysis that minimizes subjective interpretation of the results. This
      is a method of ZAP-70 assessment that could be included in a routine diagnostic
      CLL panel; however, the choice of anticoagulant and time of analysis after
      collection are critical factors in accurate assessment of ZAP-70 expression.

PMID- 16906574
TI  - Discordant results of flow cytometric ZAP-70 expression status in B-CLL samples
      if different gating strategies are applied.
AB  - BACKGROUND: Recent studies have identified ZAP-70 expression status as an
      excellent prognostic parameter in chronic lymphocytic leukemia (CLL). ZAP-70
      expression can be determined by direct antibody staining followed by flow
      cytometric analysis. However, there are currently several different gating
      strategies for analysis. We compared those strategies for ZAP-70 expression
      analysis. METHODS: One hundred and one patients with B-CLL were analyzed
      employing a directly labeled alexa-fluor-488-ZAP-70-antibody. In 27 cases, we
      additionally measured and analyzed ZAP-70 expression, together with healthy
      controls as described previously. RESULTS: Applying either T-/NK-cell isotype or
      healthy control analysis strategies on patient samples that were processed in
      parallel revealed discrepant results in 48% (12/25) of all cases. Taken together
      with the 74 B-CLL patients, who were analyzed with regard to average reference
      values, disconcordant results were obtained in 58% of the samples. We demonstrate
      that high variances in ZAP-70 T-/NK-cell staining within B-CLL patients, paired
      with a close proximity of ZAP-70 B-cell values to the suggested cut-off levels,
      may lead to interpretation difficulties of ZAP-70 status. CONCLUSIONS: We
      conclude that different gating strategies for determining flow cytometric ZAP-70
      expression status produce highly discordant results. Further standardization is
      required before ZAP-70 can be used as a reliable prognostic parameter in
      immunophenotyping of B-CLL.

PMID- 16906575
TI  - ZAP-70 in CLL: towards standardization of a biomarker for patient management:
      history of clinical cytometry special issue.

PMID- 16906576
TI  - What is ZAP-70?
AB  - Zap-70, a crucial molecule for the selective activation of T cells, through its
      interaction with the zeta chain of the TCR/CD3 complex, is a tyrosine kinase.
      This well studied molecule has gained a renewed interest upon the demonstration
      of its transduction and expression in B cells from patients with chronic
      lymphocytic leukemia. Here the major characteristics of this cytosolic protein
      are reviewed, as well as its expression in various cell types and some
      indications about its detection.

PMID- 16906577
TI  - Comparison of methods for determining zeta-chain associated protein - 70 (ZAP-70)
      expression in patients with B-cell chronic lymphocytic leukemia (B-CLL).
AB  - BACKGROUND: Zeta-chain associated protein of 70kDa (ZAP-70) is the most promising
      surrogate marker for the immunoglobulin heavy chain variable region (IgV(H))
      mutation status in B-cell chronic lymphocytic leukemia (B-CLL). Crespo et al.
      proposed the detection of ZAP-70 by flow cytometry. Recently several novel
      monoclonal antibodies appeared on market. METHODS: We compared different staining
      methods utilizing monoclonal antibodies (moAb) against ZAP-70: anti-ZAP-70 PE,
      clone 1E7.2, anti-ZAP-70 PE, clone 17A/P-ZAP70 directly stained with flourochrome
      as well as anti-ZAP-70 antibody, clone 2F3.2 stained with Zenontrade mark Alexa
      Fluor(R) 488 Labeling Kit. Additionally different reagents for permeabilization
      such as IntraPrep, FIX & PERM, Perm/Wash and 70% ethanol/paraformaldehyde were
      used to find the most clinically relevant and easy assay to determine ZAP-70
      expression in B-CLL. Moreover we compared results of ZAP-70 expression assessed
      by whole blood protocol with those obtained using-peripheral mononuclear cells
      isolated from whole blood. RESULTS: Anti-ZAP-70 moAb clone 17A/P-ZAP70 gave
      elevated results for all B-CLL patients as well as healthy controls. Staining
      with anti-ZAP-70 moAb clone 1E7.2 and anti-ZAP-70 moAb clone 2F3.2 was effective
      in distinguishing negative and positive cells for ZAP-70 protein expression. Not
      statistically significant discrepancies of ZAP-70 expression were noticed between
      different fixation and permeabilization methods. CONCLUSION: Basing on results
      obtained during this study we can recommend use of anti-ZAP-70 PE, clone 1E7.2
      moAb utilizing whole blood protocol with commercial kits for permeabilization as
      an easy method that brings compatible results to the original method proposed by
      Crespo et al.

PMID- 16906578
TI  - Comparison of bone marrow and peripheral blood ZAP-70 status examined by flow
      cytometric immunophenotyping in patients with chronic lymphocytic leukemia.
AB  - BACKGROUND: : The mutational status of the immunoglobulin heavy chain variable
      gene in patients with chronic lymphocytic leukemia correlates with prognosis.
      Patients with mutated IgVH genes fare better than those with unmutated genes.
      Gene expression profiling studies identified the tyrosine kinase ZAP-70 to be
      expressed in unmutated CLL samples. Flow cytometric examination of ZAP-70
      expression in tumor cells has been proposed to be a convenient surrogate marker
      for IgVH mutational status. However, a few studies have shown a small number of
      discordant results between ZAP-70 positivity, IgVH mutational status, and
      clinical outcome. There have been no reported studies comparing bone marrow
      samples with peripheral blood for ZAP-70 expression in CLL patients. METHODS: :
      We searched our flow cytometry files from October 2004 through April 2006 and
      identified CLL in 311 bone marrow and peripheral blood specimens from 256
      patients. We defined ZAP-70 positivity as greater than 30% of the CD19(+) B-cells
      above the isotype control value that coexpress ZAP-70. Statistical analyses were
      performed using the Fisher exact test and student t-test. RESULTS: : A
      significantly greater number of bone marrow specimens were positive for ZAP-70
      when compared with the number of peripheral blood specimens. Of all the ZAP-70
      negative specimens, CLL cells from bone marrow had a greater mean percentage of
      ZAP-70 positive cells when compared with the CLL cells from peripheral blood.
      Finally, six patients were identified who were ZAP-70 positive in the bone marrow
      but ZAP-70 negative in the peripheral blood. CONCLUSIONS: : These results may be
      due to either an increase in the false positive rate in bone marrow specimens or
      to an intrinsic feature of CLL cells in the compartment that is biologically
      distinct from peripheral tumor cells. As prognosis and treatment decisions may be
      based on ZAP-70 results from either specimen type, it is prudent to further
      examine this observation. (c) 2006 International Society for Analytical Cytology.

PMID- 16906579
TI  - Flow cytometry for ZAP-70: New colors for chronic lymphocytic leukemia.
AB  - ZAP-70 has become one of the most studied prognostic markers in Chronic
      Lymphocytic Leukemia (CLL). ZAP-70 is remarkable in many ways: ZAP-70 has been
      identified as the best discriminating gene between prognostically distinct CLL
      subtypes using large scale gene expression profiling; ZAP-70 has been shown to
      enhance signal transduction in CLL B-cells and therefore could contribute to
      disease progression; and ZAP-70 is one of the rare examples of an intracellular
      target considered for clinical flow cytometry. This issue attests to the enormous
      effort and the steady progress made in overcoming technical challenges of testing
      for ZAP-70 expression and sets the foundation for a successful translation of
      this important marker into clinical practice. Despite the best effort, one will
      likely have to accept that not all cases can be clearly assigned to one or the
      other group, given that ZAP-70 expression between CLL patients falls along a
      continuum from absent to high. Nevertheless, ZAP-70 expression could become a key
      parameter to guide patients towards risk adapted treatment strategies in
      prospective clinical trials.

PMID- 16906580
TI  - Clinical implications of ZAP-70 expressionin chronic lymphocytic leukemia.
AB  - Chronic lymphocytic leukemia (CLL) is a disease with an extremely heterogeneous
      prognosis. Because of this and because of the lack of a truly effective therapy,
      treatment of CLL must be adapted to the individual risk of each patient. Over the
      last quarter of century, prognosis of patients with CLL has been based on
      clinical features. In the last few years a number of biological prognostic
      parameters have been identified. Among them, the expression of ZAP-70 in
      neoplastic B lymphocytes is increasingly being recognized as of paramount
      importance to predict outcome. Patients with a low percentage (<20%) of ZAP-70
      positive neoplastic B lymphocytes have a much better prognosis that those with a
      higher proportion (>20%) of ZAP-70 positive neoplastic B lymphocytes.

PMID- 16906581
TI  - An optimized whole blood method for flow cytometric measurement of ZAP-70 protein
      expression in chronic lymphocytic leukemia.
AB  - BACKGROUND: ZAP-70 protein expression has been proposed as a marker for
      immunoglobulin heavy chain mutational status, which some studies have correlated
      with disease course in B-cell chronic lymphocytic leukemia (CLL). Studies
      published to date measuring levels of expression of ZAP-70 intracellular protein
      using flow cytometry have demonstrated poor performance, as defined by the
      difference in signal in known positive and negative lymphocyte populations.
      METHODS: A recently published method (Chow S, Hedley DW, Grom P, Magari R,
      Jacobberger JW, Shankey TV, Cytometry A 2005;67:4-17) to measure intracellular
      phospho-epitopes was optimized using a design of experiments (DOE) approach to
      provide the best separation of ZAP-70 expression in positive T- or NK-cells as
      compared to negative B-cells in peripheral blood samples. A number of
      commercially available anti-ZAP-70 antibody-conjugates were screened using this
      methodology, and the antibody-conjugate showing the best performance was chosen
      to develop a four-color, five antibody assays to measure ZAP-70 levels in whole
      blood specimens. RESULTS: Using the optimized fixation and permeabilization
      method, improvement in assay performance (signal-to-noise, S/N) was seen in most
      of the antibodies tested. The custom SBZAP conjugate gave the best S/N when used
      in conjunction with this optimized fixation /permeabilization method. In
      conjunction with carefully standardized instrument set-up protocols, we obtained
      both intra- and interlaboratory reproducibility in the analysis of ZAP-70
      expression in whole blood samples from normal and CLL patients. CONCLUSIONS: The
      development of a sensitive, specific and highly reproducible ZAP-70 assay
      represents only the first essential step for any clinical assay. The universal
      implementation of a validated data analysis method and the establishment of
      methodology-based cutoff points for clinical outcomes must next be established
      before ZAP-70 protein analysis can be routinely implemented in the clinical
      laboratory.

PMID- 16906582
TI  - Kolmogorov-Smirnov statistical test for analysis of ZAP-70 expression in B-CLL,
      compared with quantitative PCR and IgV(H) mutation status.
AB  - BACKGROUND: ZAP-70 has been proposed as a surrogate marker for immunoglobulin
      heavy-chain variable region (IgV(H)) mutation status, which is known as a
      prognostic marker in B-cell chronic lymphocytic leukemia (CLL). The flow
      cytometric analysis of ZAP-70 suffers from difficulties in standardization and
      interpretation. We applied the Kolmogorov-Smirnov (KS) statistical test to make
      analysis more straightforward. METHODS: We examined ZAP-70 expression by flow
      cytometry in 53 patients with CLL. Analysis was performed as initially described
      by Crespo et al. (New England J Med 2003; 348:1764-1775) and alternatively by
      application of the KS statistical test comparing T cells with B cells. Receiver
      operating-characteristics (ROC)-curve analyses were performed to determine the
      optimal cut-off values for ZAP-70 measured by the two approaches. ZAP-70 protein
      expression was compared with ZAP-70 mRNA expression measured by a quantitative
      PCR (qPCR) and with the IgV(H) mutation status. RESULTS: Both flow cytometric
      analyses correlated well with the molecular technique and proved to be of equal
      value in predicting the IgV(H) mutation status. Applying the KS test is
      reproducible, simple, straightforward, and overcomes a number of difficulties
      encountered in the Crespo-method. CONCLUSIONS: The KS statistical test is an
      essential part of the software delivered with modern routine analytical flow
      cytometers and is well suited for analysis of ZAP-70 expression in CLL.

PMID- 16906583
TI  - Clinical utility of assessing ZAP-70 and CD38 in chronic lymphocytic leukemia.

PMID- 16906584
TI  - Use of a blocking antibody method for the flow cytometric measurement of ZAP-70
      in B-CLL.
AB  - BACKGROUND: In this study we developed a method to measure the amount of ZAP-70
      [zeta accessory protein] in B-CLL cells without relying on the ZAP-70 expression
      of patient B or T cells to normalize fluorescence intensity. METHODS: B-CLL cells
      were fixed with formaldehyde before surface staining with gating antibodies
      CD19PC5 and CD5FITC. The cells were permeabilized with saponin, and the ZAP-70
      antigen was blocked in one tube with unlabeled antibody to ZAP-70 [clone 1E7.2].
      Zap-70-PE was then added to this tube. ZAP-70-PE was added to a second tube
      without unlabeled antibody to ZAP-70. The mean fluorescence intensity of the ZAP
      70 in the tube without unlabeled antibody divided by the mean fluorescence
      intensity of the ZAP-70 in the tube with unlabeled antibody equals the RATIO of
      total fluorescence to non-specific ZAP-70 fluorescence in the B-CLL cells. In a
      second method of analysis, a region is created in the histogram showing ZAP-70
      fluorescence intensity in the tube with unlabeled antibody to ZAP-70. This region
      is set to 0.9% positive cells. This same region is then used to measure the %
      positive [%POS] ZAP-70 cells in the tube without unlabeled antibody to ZAP-70.
      The brighter the ZAP-70 fluorescence above the non-specific background, the
      higher the %POS. RESULTS: Due to the varying amount of non-specific staining
      between patient B-CLL cells and other cells, the blocking antibody method yielded
      a more quantitative and reproducible measure of ZAP-70 in B-CLL cells than other
      methods, which use the ratio of B-CLL fluorescence to normal B or T-cell
      fluorescence. Using this improved method, ZAP-70 was determined to be negative if
      the RATIO was less than 2:1 and positive if the RATIO was greater than 2:1. ZAP
      70 was determined to be negative if the %POS was less than 5% and positive if the
      %POS was greater than 5%, a cut-off value lower than previous values published,
      due to exclusion of non-specific staining. Both cut-offs were based upon patient
      specimen distribution profiling. CONCLUSIONS: Use of a blocking antibody resulted
      in a robust, reproducible clinical B-CLL assay that is not influenced by the need
      to measure the amount of ZAP-70 in other cells. ZAP-70 results segre gate
      patients into indolent and aggressive groups suggested by published clinical
      outcomes.

PMID- 16906585
TI  - Variations in the detection of ZAP-70 in chronic lymphocytic leukemia: Comparison
      with IgV(H) mutation analysis.
AB  - Lack of immunoglobulin heavy chain genes (IgV(H)) mutation in patients with
      chronic lymphocytic leukemia (CLL) is associated with rapid disease progression
      and shorter survival. The zeta-chain (T-cell receptor) associated protein kinase
      70 kDa (ZAP-70) has been reported to be a surrogate marker for IgV(H) mutation
      status, and its expression in leukemic cells correlates with unmutated IgV(H).
      However, ZAP-70 detection by flow cytometry varies significantly dependant on the
      antibodies used, the method of performing the assay, and the condition of the
      cells in the specimen. The clinical value of ZAP-70 testing when samples are
      shipped under poorly controlled conditions is not known. Furthermore, testing in
      a research environment may differ from testing in a routine clinical laboratory.
      We validated an assay for ZAP-70 by comparing results with clinical outcome and
      the mutation status of the IgV(H). Using stored samples, we show significant
      correlation between ZAP-70 expression and clinical outcome as well as IgV(H)
      mutation at a cut-off point of 15%. While positive samples (>15% positivity)
      remain positive when kept in the laboratory environment for 48 h after initial
      testing, results obtained from samples from CLL patients tested after shipping at
      room temperature for routine testing showed no correlation with IgV(H) mutation
      status when 15% cut-off was used. In these samples, cut-point of 10% correlated
      with the IgV(H) mutation (P = 0.0001). This data suggests that although ZAP-70
      positivity correlates with IgV(H) mutation status and survival, variations in
      sample handling and preparation may influence results. We show that IgV(H)
      mutation results, unlike ZAP-70 remain correlated with CD38 expression and beta-2
      microglobulin in shipped samples, and ZAP-70 testing should not be used as the
      sole criterion for stratifying patients for therapy.

PMID- 16906586
TI  - A standardized ZAP-70 assay--lessons learned in the trenches.
AB  - BACKGROUND: The disease of chronic lymphocytic leukemia (CLL) has been shown to
      exhibit varying clinical outcomes based on reported laboratory parameters. One of
      these parameters involves the measurement of the protein levels of zeta
      associated protein (ZAP-70) in CLL cells. A standardized assay has not yet
      reached consensus in the clinical cytometry community. METHODS: We developed a
      system using the 8-peak Rainbow beads as our fluorescence calibrator along with a
      fixed cell control. Using a panel of CD19-PE, CD5-FITC, and ZAP-70-Alexa 647, we
      stained normal whole blood, and blood and bone marrow from patients with CLL to
      determine the level of ZAP-70 expression in T-cell, B-cell, and CLL-cell
      populations. ZAP-70 expression was reported in molecules equivalent fluorescence
      (MEFL) based on the calibration of the flow cytometer with the 8-peak Rainbow
      beads. RESULTS: Daily assay performance as well as operating MEFL defined ranges
      for ZAP-70 detection in CLL were developed. A rank-order, nonparametric approach
      to reference ranges was used to assign a cutoff for "negative" as well as ranges
      for "intermediate" and "positive" staining using T and B cells from a pool of 50
      normal subjects, and CLL cells from 395 patients. The assay was validated in a
      multi-institutional study and has demonstrated correlation with published
      techniques. Since its initial development, the assay has been implemented at two
      additional laboratory sites and has been shown to produce reproducible,
      correlated data at all sites. CONCLUSIONS: Strict adherence to standardization
      can yield an assay that is predictable, reliable, and reproducible as well as
      capable of multisite implementation. The Rainbow beads provide a common platform
      for system calibration. The fixed cell culture controls provide a common target
      to test antibody. The final level of control tests the sensitivity of ZAP-70
      detection in a normal peripheral blood sample stained along with the submitted
      CLL patients. The acceptance/rejection of test results must meet all three levels
      of control before patient results are reported.

PMID- 16906587
TI  - ZAP-70 expression in B-cell chronic lymphocytic leukemia: evaluation by external
      (isotypic) or internal (T/NK cells) controls and correlation with IgV(H)
      mutations.
AB  - BACKGROUND: Expression of T cell specific zeta-associated protein 70 (ZAP-70) by
      B-cell chronic lymphocytic leukemia (B-CLL) cells, as investigated by flow
      cytometry, has both prognostic relevance and predictive power as surrogate for
      immunoglobulin heavy chain variable region (IgV(H)) mutations, although a
      standardization of the cytometric protocol is still lacking. METHODS: Flow
      cytometric analyses for ZAP-70 were performed in peripheral blood samples from
      145 B-CLL (124 with IgV(H) mutations) by a standard three-color protocol.
      Identification of ZAP-70(+) cell population was based on an external negative
      control, i.e., the isotypic control (ISO method) or an internal positive control,
      i.e., the population of residual normal T/NK cells (TNK method). A comparison
      between these two approaches was performed. RESULTS: While 86/145 cases were
      concordant as for ZAP-70 expression according to the two methods (ISO(+)TNK(+) or
      ISO(-)TNK(-)), 59/145 cases had discordant ZAP-70 expression, mainly (56/59)
      showing a ISO(+)TNK(-) profile. These latter cases express higher levels of ZAP
      70 in their normal T cell component. Moreover, discordant ISO(+)TNK(-) cases had
      a IgV(H) gene mutation profile similar to that of concordantly positive cases and
      different from ZAP-70 concordantly negative B-CLL. CONCLUSION: Analysis of ZAP-70
      expression by B-CLL cells by using the ISO method allows to overcome the
      variability in the expression of ZAP-70 by residual T cells and yields a better
      correlation with IgV(H) gene mutations. A receiver operating characteristic
      analysis suggests to employ a higher cut-off than the commonly used 20%. A
      parallel evaluation of the prognostic value of ZAP-70 expression, as determined
      according to the ISO and TNK methods, is still needed.

PMID- 16906589
TI  - Manifestations of West Nile neuroinvasive disease.
AB  - Since its introduction to North America in 1999, West Nile virus, an arthropod
      borne flavivirus, has become the most significant cause of epidemic encephalitis
      in the western hemisphere. While most human infections with the virus are
      asymptomatic and the majority of symptomatic persons experience febrile illness,
      severe neurologic manifestations, including meningitis, encephalitis, and
      poliomyelitis may be seen. This review summarizes the virology, epidemiology and
      pathogenesis of human infection with West Nile virus, and details recent advances
      in our understanding of the pathophysiology and various clinical manifestations
      of infection.

PMID- 16906588
TI  - Evaluation of ZAP-70 expression by flow cytometry in chronic lymphocytic
      leukemia: A multicentric international harmonization process.
AB  - The clinical course of patients with chronic lymphocytic leukemia (CLL) is
      heterogeneous with some patients requiring early therapy whereas others will not
      be treated for years. The evaluation of an individual CLL patient's prognosis
      remains a problematic issue. The presence or absence of somatic mutations in the
      IgVH genes is currently the gold-standard prognostic factor, but this technique
      is labor intensive and costly. Genomic studies uncovered that 70 kDa zeta
      associated protein (ZAP-70) expression was associated with unmutated IgVH genes
      and ZAP-70 protein expression was proposed as a surrogate for somatic mutational
      status. Among the available techniques for ZAP-70 detection, flow cytometry is
      most preferable as it allows the simultaneous quantification of ZAP-70 protein
      expression levels in CLL cells and residual normal lymphocyte subsets. However,
      several factors introduce variability in the results reported from different
      laboratories; these factors include the anti-ZAP-70 antibody clone and conjugate,
      the staining procedure, the gating strategy, and the method of reporting the
      results. The need for standardization of the approach led to the organization of
      an international working group focused on harmonizing all aspects of the
      technique. During this workshop, a technical consensus was reached on the methods
      for cell permeabilization and immunophenotyping procedures. An assay was then
      designed that allowed comparison of two clones of anti-ZAP-70 antibody and the
      identification of the expression of this molecule in B, T, and NK cells
      identified in a four multicolor analysis. This procedure was applied to three
      stabilized blood samples, provided by the UK NEQAS group to all participating
      members of this study, in order to minimize variability caused by sample storage
      and shipment. Analysis was performed in 20 laboratories providing interpretable
      data from 14 centers. Various gating strategies were used and the ZAP-70 levels
      were expressed as percentage positive (POS) relative to isotype control or normal
      B-cells or normal T-cells; in addition the levels were reported as a ratio of
      expression in CLL cells relative to T-cells. The reported level of ZAP-70
      expression varied greatly depending on the antibody and the method used to
      express the results. The CLL/T-cell ZAP-70 expression ratio showed a much lower
      interlaboratory variation than other reporting strategies and is recommended for
      multicenter studies. Stabilization results in decreased expression of CD19 making
      gating more difficult and therefore stabilized samples are not optimal for
      multicentric analysis of ZAP-70 expression. We assessed the variation of ZAP-70
      expression levels in fresh cells according to storage time, which demonstrated
      that ZAP-70 is labile but sufficiently stable to allow comparison using fresh
      samples distributed between labs in Europe. These studies have demonstrated
      progress toward a consensus reporting procedure, and further work is underway to
      harmonize the preparation and analysis procedures.

PMID- 16906591
TI  - Hypothermia during the infusion of cryopreserved autologous peripheral stem cell
      causes electrocardiographical changes: report of two cases.
AB  - Currently, autologous peripheral stem cell transplantation used as a therapeutic
      modality in the treatment of various hematological malignancies is gaining more
      popularity day by day. In this method, the patient's own peripheral stem cells
      are collected by a proper method and stored at -80 degrees C until they are
      reinfused into the patient after being rewarmed in water bath at 37 degrees C. A
      number of complications have been reported related to reinfusion of the
      cryopreserved cells into the patient. These may include noncardiovascular
      complications such as nausea, vomiting, flushing, abdominal pain, chest
      discomfort, and headache, as well as cardiovascular complications like
      arrhythmias, hypotension, and hypertension. Hypothermia related to rapid infusion
      has been reported as the main factor underlying the cardiovascular complications.
      Electrocardiographic findings of hypothermia include sinusal bradycardia,
      prolonged QT and PR intervals, widened QRS complexes, and J wave, which is a ECG
      abnormality characterized by supraventricular and ventricular arrhythmias. We
      here present two cases of giant J wave caused by hypothermia during infusion of
      cryopreserved autologous peripheral stem cell that is detected by ECG and
      regressed after infusion ceased.

PMID- 16906590
TI  - Depression among older people with cognitive impairment: prevalence and
      detection.
AB  - BACKGROUND: Past research has demonstrated that there is a high level of
      depression among older people, particularly for those with cognitive impairment
      and those in residential care. The current study was designed to determine the
      prevalence of depression among older people in hostels with cognitive impairment
      using a structured diagnostic interview. A further aim was to determine an
      appropriate screening instrument to detect depression within this population. It
      was also designed to evaluate the extent to which depression among these older
      people had previously been detected. METHOD: Five commonly used depression scales
      were administered and compared to the results of the diagnostic interview.
      RESULTS: The results demonstrated that 38.9% of older people were diagnosed with
      depression, but that only 50% of these people had been previously diagnosed with
      this disorder. All scales showed some level of validity to detect depression.
      CONCLUSIONS: The implications of these findings for our understanding of
      depression among older people with cognitive impairment are discussed.

PMID- 16906592
TI  - The successful treatment of refractory autoimmune hemolytic anemia with rituximab
      in a patient with chronic lymphocytic leukemia.
AB  - The most frequent autoimmune complication in chronic lymphocytic leukemia (CLL)
      is autoimmune hemolytic anemia (AIHA). There are various treatment modalities;
      however, there is not much experience with the use of the chimeric anti-CD20
      monoclonal antibody rituximab in the autoimmune complications of CLL. Here, we
      present our patient with CLL and AIHA whose AIHA was unresponsive to various
      treatment modalities. The administration of 375 mg/m(2)/day rituximab weekly for
      four cycles halted hemolysis and resulted in resolution of the patient's anemia.
      One year after therapy, the patient is well with a normal blood count. Rituximab
      might be preferred over other treatment modalities in the autoimmune
      complications of CLL because it is effective and has fewer side effects than
      other therapies.

PMID- 16906593
TI  - Pulmonary alveolar proteinosis with myeloproliferative syndrome with
      myelodysplasia: bronchoalveolar lavage reduces white blood cell count.
AB  - Pulmonary alveolar proteinosis (PAP) is a rare disorder characterized by
      surfactant component accumulation in the alveolar space. Primary PAP is likely an
      autoimmune disorder caused by antibodies to granulocyte-macrophage colony
      stimulating factor (GM-CSF). When an underlying disease causes PAP, this is
      called secondary PAP. Hematologic malignancies are an important cause of
      secondary PAP. As the pathogenesis of primary PAP has become more fully
      understood, improvements in diagnostic and therapeutic approaches have followed.
      However, when PAP is secondary to an underlying hematologic malignancy, much
      remains unclear. Here we describe for the first time a patient with hybrid
      myelodysplastic syndrome/myeloproliferative syndrome and PAP who had a marked
      decrease in her white blood cell count following a transbronchial biopsy
      accompanied by bronchoalveolar lavage (BAL). Similar significant decreases in WBC
      count accompanied clinical improvement following two unilateral BALs. Given that
      patients with pulmonary alveolar proteinosis frequently have elevated GM-CSF in
      bronchoalveolar fluid, this observation provides a unique vantage point to
      understand the pathophysiology of secondary PAP.

PMID- 16906594
TI  - Epstein-Barr virus in breast cancer: artefact or aetiological agent?
AB  - The Epstein-Barr virus (EBV) has been reported to be associated with a variety of
      different tumours; for some of these malignancies, including breast cancer, the
      association remains controversial. This might be due in part to differences in
      the methodologies used to detect EBV in tissue samples. One approach favoured by
      many groups is to use immunohistochemistry to detect an EBV protein, EBNA1, which
      is essential for the maintenance of viral latency in infected cells and therefore
      should be a good marker for the presence of the virus. However, in this issue of
      the Journal of Pathology, Hennard and colleagues report that one of the
      antibodies frequently employed to detect EBNA1 in tissue samples cross-reacts
      with the MAGE4 protein, a cancer testis antigen expressed in many cancer types.
      Their observation suggests that reports documenting an EBV association on the
      basis of reactivity with this antibody must be considered unreliable. It also re
      opens the debate about whether breast cancer is an EBV-associated disease.

PMID- 16906596
TI  - Reduction in dentin permeability using a slurry containing dicalcium phosphate
      and calcium hydroxide.
AB  - Treatments that obdurate dentin tubules have been used for reducing dentin
      hypersensitivity. The purpose of this study was to determine the effect of a
      treatment with a slurry of micron sized calcium phosphate on the hydraulic
      conductance (L(p)) of etched dentin discs in vitro. The treatment slurry was
      prepared by mixing a powder mixture of dicalcium phosphate anhydrous and calcium
      hydroxide with a solution that contained sodium fluoride and carboxymethyl
      cellulose. The mean baseline L(p) (in mL cm(-2) s(-1) H(2)O cm(-1)) was 2.07 +/-
      1.45 (mean +/- SD; n = 13)). After one treatment and 2, 4, and 7 days of
      incubation in a protein-free saliva-like solution (SLS), the mean relative L(p),
      presented as % of baseline, were 65 +/- 16, 42 +/- 27, 36 +/- 26, and 33 +/- 27
      (n = 13), respectively. The L(p) values of the baseline and treatment after
      incubation in the SLS were significantly (p < 0.05) different. Scanning electron
      microscopic examination showed partial obturation of dentin tubules in the
      treated dentin. X-ray diffraction and chemical analyses indicated the major
      product formed from the slurry was a fluoride-containing hydroxyapatite.
      Treatment appeared effective in further reducing L(p) of dentin discs after
      incubation in the SLS.

PMID- 16906597
TI  - Atorvastatin has cardiac safety at intensive cholesterol-reducing protocols for
      long term, yet its cancer-treatment doses with chemotherapy may cause
      cardiomyopathy even under coenzyme-Q10 protection.
AB  - Statins provide strong clinical benefits via reducing stroke deaths, and they are
      also considered for tumor reduction and chemo-sensitization. High dose
      atorvastatin in adults (80 mg daily, approx. 1 mg/kg) is proven to afford greater
      protection against cardiac deaths than does a standard lipid-lowering dose in
      coronary syndrome. For cancer trials, mega doses up to 30 mg/kg have been used
      for short term treatments but neither a high nor a mega-dose of atorvastatin has
      been tested for long term cardiac safety. This may be of special concern, since
      some animal studies showed deleterious effects of statins on cardiac tissue,
      which may be related with coenzymeQ (CoQ) depletion. We performed an electron
      microscopic analysis of rat hearts after low, high-or mega-dose atorvastatin
      therapy and with or without MNU (methyl-nitrosourea)-stress. MNU + daily high
      dose atorvastatin treatment for 13 months did not produce severe cardiac toxicity
      with CoQ. However, at mega doses (30 mg/kg) and with MNU, mitochondrial damage
      and myofibrillary disintegration was obvious. Strong proliferation of
      mitochondria under high dose atorvastatin therapy with CoQ may explain the lack
      of cardiotoxicity; and this finding seems to parallel recent data that statins
      induce HNF-4 and PPAR-alpha, both responsible for mitochondria-proliferation.
      Employment of statins for tumor chemo-sensitization at high-dosage and for long
      term treatments may require strategies to direct the mevalonate-entry
      differentially into cardiac and tumor cells and to develop a protocol analogous
      to folic acid salvage of methotrexate toxicity.

PMID- 16906599
TI  - Non-mosaic trisomy 22: a report of 2 cases.
AB  - Non-mosaic trisomy 22 is a common cause of first trimester miscarriage and has a
      livebirth incidence of 1 in 30,000-50,000. Consequently there is a paucity of
      information for counselling parents. Detection in the second trimester is rare.
      It is commonly associated with severe growth retardation and multiple structural
      abnormalities. Oligohydramnios is frequently seen and can make detection of other
      abnormalities difficult. The outlook is uniformly poor and survival beyond the
      first trimester may present management dilemmas. A thorough fetal assessment
      including high-resolution cytogenetics with or without FISH is required for
      counselling. Careful plans for intrapartum and neonatal management may be
      necessary. The recurrence risk is thought to be low but information is very
      limited as there have been no reported cases of recurrence. We present two case
      of non-mosaic trisomy 22 including the first to be diagnosed subsequent to
      investigation for a high serum screening Down's risk.

PMID- 16906600
TI  - Complete discrepancy between abnormal fetal karyotypes predicted by QF-PCR rapid
      testing and karyotyped cultured cells in a first-trimester CVS.
AB  - A chorion villus sample (CVS) biopsied at 11 weeks' gestation for raised nuchal
      translucency, revealed monosomy X (presumptive 45,X karyotype) by QF-PCR for
      rapid aneuploidy testing for chromosomes 13, 18, 21, X and Y. Long-term culture
      gave the karyotype: 47,XY,+ 21[66]/49,XYY,+ 21,+ 21 [22]. This discrepancy
      prompted redigestion of the combined residual villus fragments from the original
      QF-PCR assay. The repeat QF-PCR assay identified the presence of trisomy 21 and a
      Y chromosome consistent with a 47,XY,+ 21 karyotype. A double non-disjunction
      event early in embryogenesis in a 47,XY,+ 21 conceptus with subsequent cell
      lineage compartmentalisation of the three observed cell lines (45,X; 47,XY,+ 21
      and 49,XYY,+ 21,+ 21) would account for these results. This is the first reported
      case to describe complete discrepancy at diagnosis between abnormal karyotypes
      detected by QF-PCR rapid aneuploidy testing and a cultured karyotype in the same
      CVS.

PMID- 16906601
TI  - Photochemical upconversion: anthracene dimerization sensitized to visible light
      by a RuII chromophore.

PMID- 16906598
TI  - Apert syndrome: what prenatal radiographic findings should prompt its
      consideration?
AB  - Apert syndrome was diagnosed in a newborn with typical facial and digital
      features whose only detected prenatal abnormality had been agenesis of the corpus
      callosum. This prompted a review of the central nervous system findings in all
      cases of Apert syndrome treated at the Craniofacial Center Boston Children's
      Hospital between 1978 and 2004. Two of 30 patients with Apert syndrome had
      prenatal identification of mild dilatation of the lateral cerebral ventricles and
      complete agenesis of the corpus callosum (ACC) documented with both ultrasound
      and MRI. Both had the common S252W mutation of FGFR2. Though cranial and orbital
      malformations typical of Apert were eventually seen in these fetuses in the third
      trimester, even in retrospect, these were not detectable at mid second-trimester,
      ultrasound screening for congenital malformations. Hand malformations also went
      undetected in the second-trimester despite extensive imaging by experienced
      radiologists. We conclude that prenatal ultrasonographic identification of mild
      ventriculomegaly or ACC should stimulate a careful search for features of Apert
      syndrome and prompt follow-up imaging to look for bony abnormalities that have
      later onset. Prenatal molecular testing for Apert mutations should be considered
      in cases of mild ventriculomegaly and ACC.

PMID- 16906602
TI  - A new dimension in multinuclear metallocene complexes.

PMID- 16906603
TI  - Phosphole-modified poly(thiophene)s: unique postfunctionalizable conjugated
      polymers that sense elemental chalcogenides.

PMID- 16906604
TI  - Application of solvent-directed assembly of block copolymers to the synthesis of
      nanostructured materials with low dielectric constants.

PMID- 16906605
TI  - A zinc-zinc-bonded compound and its derivatives bridged by one or two hydrogen
      atoms: a new type of Zn-Zn bonding.

PMID- 16906606
TI  - Self-regenerating Rh- and Pt-based perovskite catalysts for automotive-emissions
      control.

PMID- 16906607
TI  - Through-space conjugated polymers based on cyclophanes.
AB  - Conjugated polymers display unique electronic and optical properties, which favor
      their use in applications as optoelectronic materials and molecular devices.
      Despite the recent remarkable progress in the chemistry of conjugated polymers,
      the synthesis of conjugated polymers containing cyclophane units in the main
      chain is limited to only a few examples. This Minireview presents recent
      developments in the synthesis, properties, and applications of through-space
      conjugated polymers based on cyclophanes.

PMID- 16906608
TI  - Onset of crystalline order in 1-nonanethiol monolayers deposited from solution.

PMID- 16906609
TI  - Thermoresponsive micelles from oligopeptide-grafted cyclotriphosphazenes.

PMID- 16906610
TI  - Isostructural coordination capsules for a series of 10 different d5-d10
      transition-metal ions.

PMID- 16906611
TI  - Radical alkylation of bis(silyloxy)enamine derivatives of organic nitro
      compounds.

PMID- 16906612
TI  - Synthesis and study of Janus bis(carbene)s and their transition-metal complexes.

PMID- 16906613
TI  - Highly diastereo- and enantioselective Mukaiyama aldol reactions catalyzed by
      hydrogen bonding.

PMID- 16906614
TI  - Auxetics at the molecular level: a negative poisson's ratio in molecular rods.

PMID- 16906615
TI  - Designed boronate ligands for glucose-selective holographic sensors.
AB  - In this study, 2-acrylamidophenylboronate (2-APB) was synthesised and its ability
      to bind with glucose was investigated both in solution and when integrated into a
      holographic sensor. Multiple forms of 2-APB, resulting from the neighbouring
      effect of the amido group with the boronic acid through an intramolecular B--O
      coordinated interaction, were shown to exist in solution by using multinuclear
      NMR spectrometry. It was found that 2-APB predominantly adopts a zwitterionic
      tetrahedral form at physiological pH values. The complex formation of 2-APB with
      glucose and lactate was investigated in DMSO; 2-APB favours binding with glucose
      rather than lactate and generates a five-membered-ring complex. Furthermore, a 2
      APB-based holographic sensor displayed a significant response to glucose with
      little interference from lactate, and with no dependence on pH in the
      physiological pH range. These features suggest that the new ligand 2-APB is a
      potential candidate for the development of glucose-selective sensors.

PMID- 16906616
TI  - Total synthesis of pseudolaric acid A.

PMID- 16906617
TI  - A general approach to the covalent immobilization of single polymers.

PMID- 16906618
TI  - Anion-templated syntheses of pseudopeptidic macrocycles.

PMID- 16906619
TI  - Contribution of ligand desolvation to binding thermodynamics in a ligand-protein
      interaction.

PMID- 16906620
TI  - Quantum chemical calculations predict the diphenyl diuranium compound [PhUUPh] to
      have a stable 1Ag ground state.

PMID- 16906621
TI  - Total syntheses of the antibacterial natural product abyssomicin C.

PMID- 16906622
TI  - Orthostatic hypotension in Parkinson's disease: association with cognitive
      decline?
AB  - BACKGROUND: Orthostatic hypotension is common in Lewy body disorders and may be
      related to disease progression and the spread of Lewy body pathology. We
      therefore hypothesize that PD patients with orthostatic hypotension (OH) have a
      different cognitive profile compared to PD patients without OH. METHODS: This
      cross-sectional study included 175 PD patients. Blood pressure (BP) was measured
      with a validated digital blood pressure monitor and patients with a systolic BP
      drop of > or =20 mmHg or a systolic pressure of <90 mm Hg after standing were
      considered to have OH. Cognition was assessed using MMSE extended by a selection
      of computerized cognitive tests focusing on reaction time, sustained attention,
      working memory and episodic verbal and visual memory. RESULTS: Eighty-seven
      (49.7%) of the PD patients had OH. These patients were significantly more
      impaired in sustained attention and visual episodic memory compared to PD
      patients without OH. CONCLUSION: We conclude that there are differences in the
      neuropsychological performance of patients with PD and OH, supporting the
      hypothesis that OH might be a marker for disease progression and cognitive
      decline in PD.

PMID- 16906623
TI  - Psychological processes underlying delusional thinking in late-onset psychosis: a
      preliminary investigation.
AB  - BACKGROUND AND AIMS: It has been suggested that delusions may serve as a defence
      against negative self-representations. The present study investigated general
      psychological well-being and evidence for defensive emotional processes among
      people with late-onset psychosis. METHOD: The performance and responses of older
      people with late-onset psychosis (n = 13), older people with depression (n = 15),
      and age-matched healthy controls (n = 15) were compared in a cross-sectional
      design. Participants rated their own levels of depression and self-esteem, and
      completed an emotional Stroop task to establish whether there was evidence of
      implicit depression in the absence of explicit acknowledgement. Participants
      rated themselves on a number of personal attributes in relation to two life
      stages to generate discrepancies in 'actual', 'ideal' and 'other' self-concepts,
      and completed measures of their perceptions of current and past psychological
      well-being. RESULTS: People with late-onset psychosis showed no evidence of overt
      depression or low-self esteem. All three groups showed an attentional bias to
      depression-related and age-related words, although response times overall were
      faster for controls. The psychosis group showed no discrepancies between either
      their past or their current 'actual' and 'other' self-concepts, suggesting that
      they do not have more negative views about how others see them. CONCLUSIONS:
      Evidence from this study does not support the application of the 'delusion-as
      defence' model to late-onset psychosis, but methodological constraints must be
      borne in mind when interpreting the findings.

PMID- 16906624
TI  - A family-based model to predict fear of recurrence for cancer survivors and their
      caregivers.
AB  - Although fear of cancer recurrence is a great concern among survivors and their
      families, few studies have examined predictors of fear of recurrence. The purpose
      of this study was to identify factors associated with fear of recurrence in a
      population-based sample (N = 246) and determine if survivors and family
      caregivers influenced one another's fear of recurrence. A family framework guided
      the study and analyses included multilevel modeling using the Actor-Partner
      Interdependence Model. Results indicated that survivors and family caregivers
      influenced each other's fear of recurrence and that caregivers had significantly
      more fear of recurrence than survivors. More family stressors, less positive
      meaning of the illness, and age were related to elevated fear of cancer
      recurrence for both survivors and caregivers.

PMID- 16906625
TI  - Standardized audiotape versus recorded consultation to enhance informed consent
      to a clinical trial in breast oncology.
AB  - BACKGROUND: The purpose of this study was to systematically compare two audiotape
      formats for the delivery of information relevant to informed consent to
      participate in a clinical trial in breast oncology, and to establish the
      feasibility of adding a consultation recording protocol to a clinical treatment
      trial. METHOD: Participants were 69 women with newly diagnosed breast cancer and
      21 oncologists from 5 Canadian cancer centers. Patients were block randomized to
      one of three groups: 1. standardized audiotape; 2. consultation audiotape; or 3.
      both audiotapes. Patients received their tapes immediately following the clinical
      trial consultation. Patient outcomes included perception of being informed about
      clinical trials, knowledge of information relevant to providing informed consent
      to a clinical trial, and satisfaction with communication during the consultation.
      RESULTS: The consultation audiotapes contained less trial-related information
      than the standardized audiotape but there were no differences in clinical trial
      knowledge or perception of being informed across the intervention groups.
      Patients expressed a marginally significant preference for consultation
      audiotapes over standardized audiotapes. CONCLUSIONS: Patients tended to prefer
      receiving an audiotape of their own consultation over a standardized audiotape.
      The majority of oncologists considered the audiotape intervention feasible but
      were less enthusiastic about being involved in a larger study given the accrual
      challenges that arose when trying to "piggy-back" one randomized controlled trial
      on an existing clinical trial.

PMID- 16906626
TI  - The spectrum of thyroid disorders in adult type 1 diabetes mellitus.
AB  - BACKGROUND: Thyroid disorders such as goiter, nodules, autoimmune thyroid disease
      and thyroid dysfunction have rarely been investigated in adult type 1 diabetes
      mellitus. Our aim was to study the spectrum of thyroid disorders in adult type 1
      diabetic subjects and compare them with results obtained from a sample of the
      general adult population. METHODS: The study population comprised 224 type 1
      diabetic and 3481 non-diabetic subjects aged 20-69 years. Thyroid function (TSH,
      FT3 and FT4) and serum autoantibodies to thyroperoxidase (anti-TPO-Ab) were
      evaluated from blood samples. Thyroid structure and size were measured by
      ultrasound. RESULTS: Type 1 diabetic subjects had a higher risk of known thyroid
      disease [odds ratio (OR) 1.78, 95% confidence interval (CI) 1.11-2.85], a lower
      risk of goiter (OR 0.73; 95%-CI 0.54-0.99) and nodules (OR 0.54; 95%-CI 0.35
      0.85), and a higher risk of anti-TPO-Ab >200 IU/mL (OR 1.94; 95%-CI 1.28-2.95)
      compared to the reference population. Furthermore, diabetic subjects had lower
      serum FT3 levels than the non-diabetic references (adjusted mean 5.00 pmol/L; 95%
      CI 4.88-5.12 pmol/L versus 5.27 pmol/L; 95%-CI 5.24-5.30 pmol/L). CONCLUSIONS:
      Adult type 1 diabetes mellitus is associated with a decreased risk of goiter and
      nodules and an increased risk of thyroid autoimmunity. A diabetes-related low T3
      syndrome may contribute to the differences in thyroid function between type 1
      diabetic and non-diabetic subjects.

PMID- 16906627
TI  - Acute exercise stimulates macrophage function: possible role of NF-kappaB
      pathways.
AB  - Moderate physical activity when performed on a regular basis presents a number of
      benefits to the whole organism, especially regarding immune system function, such
      as augmenting resistance to infections and to cancer growth. Although glutamine
      production by active muscle cells as well as neuroendocrine alterations mediated
      by the chronic adaptation to exercise may play a role, the entire mechanism by
      which exercise makes the immune system aware of challenges remains mostly
      uncovered. This is particularly true for the effects of an acute exercise session
      on immune function. In this work, circulating monocytes/macrophages from
      sedentary rats submitted to an acute (1 h) swimming session were tested for the
      ability of phagocytosing zymosan particles, phorbol myristate acetate (PMA)
      induced hydrogen peroxide production, nitric oxide (NO) release (assessed by
      nitrate and nitrite production) and the expression of NO synthases (NOS-1, NOS-2
      and NOS-3). The results showed that an exercise bout induced a 2.4-fold rise in
      macrophage phagocytic capacity (p = 0.0041), a 9.6-fold elevation in PMA-induced
      hydrogen peroxide release into the incubation media (1-h, p = 0.0022) and a 95.5%
      augmentation in nitrite basal production (1-h incubation; p = 0.0220), which was
      associated with a marked expression of NOS-2 (the inducible NOS isoform; p =
      0.0319), but not in other NOS gene products. Although NOS-2 expression is nuclear
      factor-kappaB (NF-kappaB)-dependent, no systemic oxidative stress was found, as
      inferred from the data of plasma TBARS and glutathione disulphide (GSSG) to
      glutathione (GSH) ratio in circulating blood erythrocytes which remained constant
      after the acute exercise. Also, no stressful situation seemed to be faced by
      monocytes/macrophages, since the expression of the 70-kDa heat shock protein
      (HSP70) remained unchanged. We conclude that NF-kappaB-dependent induction of NOS
      2 and macrophage activation must be related to local factor(s) produced in the
      surroundings of monocytes/macrophages.

PMID- 16906628
TI  - Trends in potentially inappropriate prescribing amongst older UK primary care
      patients.
AB  - PURPOSE: To examine trends in UK primary care prescribing of medications
      potentially inappropriate for older people in the context of published
      international data. METHODS: Analysis of routinely collected anonymised
      computerised patient records in 131 UK general practices (approximately 162,000
      registered patients annually aged >or=65 years) providing data to the DIN-LINK
      database between 1994 and 2003. In each year, we identified patients prescribed
      drugs classified by the 2003 Beers criteria as potentially inappropriate for
      older people. RESULTS: The level of potentially inappropriate prescribing
      remained steady over time: in 2003 32.2% of patients received any Beers drug, and
      20.5% received a drug categorised as potentially "high risk"; percentages had
      been 32.9% and 21.4% respectively in 1994. In 2003, co-proxamol (93.7/1000
      patients), benzodiazepines (52.4/1000 patients) and amitriptyline (45.4/1000,
      mainly at low doses) were the most frequently prescribed potentially
      inappropriate drugs. If co-proxamol (now being withdrawn) and low-dose
      amitriptyline (appropriate for neuropathic pain) are excluded, 24.8% of patients
      still received a potentially inappropriate prescription in 2003. CONCLUSIONS:
      Prescription of potentially inappropriate medication, particularly
      benzodiazepines, to older people remains at a high level in the UK. Levels were
      higher than those seen in published data from the Netherlands, however the low
      rate of co-proxamol prescribing in the Netherlands explains much, but not all, of
      the difference. Future international comparisons, based on more careful
      delineation of the criteria, may play a valuable role in pharmaco-vigilance and
      can identify areas where regulation of prescribing may reduce risks to older
      patients.

PMID- 16906629
TI  - Lying to people with dementia: developing ethical guidelines for care settings.

PMID- 16906631
TI  - Effectiveness of acetylcholinesterase inhibitors: diagnosis and severity as
      predictors of response in routine practice.
AB  - BACKGROUND: Evidence from open label studies has indicated that patients with
      dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) do better
      than those with other diagnoses, including Alzheimer's disease (AD). In addition,
      those with dementia of moderate severity do better than those with mild severity.
      METHOD: Data collected for the monitoring of cholinesterase inhibitor prescribing
      in Oxfordshire over four years were supplemented with retrospective case notes
      inspection. 'Clinical response' was defined as improvement sufficient to merit
      continuation of therapy. A mini-mental state examination (MMSE) improvement of 2
      or more points was defined as a 'cognitive response'. RESULTS: Medication was
      prescribed for 1322 patients and outcome data was available on 1250.
      Subsequently, 939 patients were reassessed after a mean of 120 days (SD 64.1).
      Medication was discontinued early by 311, mainly due to side effects. Of those
      who reached reassessment, 82% (771 of 939) were clinical responders and 37% (232
      of 622) were cognitive responders. Overall, MMSE scores improved by +0.6 points
      [95% Confidence Intervals (CI) 0.3-0.9] and by +1.0 points (95% CI 0.7-1.3) in
      clinical responders; and deteriorated -1.5 points (95% CI -0.9--2.1) in clinical
      non-responders. A greater probability of clinical response was seen for DLB/PDD
      compared to AD patients (Odds Ratio (OR) = 2.28, 95% CI 1.07-4.89], and in men
      (OR = 1.51, 95% CI 1.02-2.23). A positive cognitive response was predicted by
      DLB/PDD compared to AD (OR = 2.07, 95% CI 1.16-3.70), moderate dementia compared
      to mild dementia (OR = 3.90, 95% CI 2.75-5.52), and by increasing age (OR 1.03
      for each incremental year, 95% CI 1.01-1.06). Those with moderate dementia were
      not more likely to have a positive clinical response than those with mild
      dementia. CONCLUSIONS: DLB/PDD patients were more likely to be both clinical and
      cognitive responders than those with AD. The finding that cognitive, but not
      clinical, response was more likely in those with moderate dementia than in those
      with mild dementia accords with the findings from randomised studies in the
      January 2006 revision of the NICE Appraisal Consultation Document.

PMID- 16906630
TI  - Cognitive predictors of functional decline in vascular dementia.
AB  - BACKGROUND: This study examined changes in cognitive-functional relationships in
      vascular dementia (VaD) over the course of one year. METHODS: Twenty-four
      patients with probable VaD were administered the Dementia Rating Scale (DRS).
      Caregivers completed an informant-based measure of instrumental (IADL) and basic
      activities of daily living (BADL). Follow-up assessment was conducted one-year
      post-baseline. RESULTS: Logistic regression revealed that changes in the DRS
      Initiation/Perseveration and DRS Memory subscales were significantly associated
      with declines in IADLs and BADLs, respectively. CONCLUSIONS: Among patients with
      VaD, longitudinal changes in IADLs and BADLs are most strongly associated with
      changes in executive functioning and memory abilities, respectively. Findings
      suggest that different cognitive functions subserve complex instrumental and
      rote, habituated basic functional activities, and neuropsychological screening
      measures are useful in the prediction of such functional changes.

PMID- 16906632
TI  - Validation of the Chinese Challenging Behaviour Scale: clinical correlates of
      challenging behaviours in nursing home residents with dementia.
AB  - BACKGROUND: Behavioural and psychological symptoms of dementia (BPSD) are
      associated with considerable burden to patients with dementia and their
      caregivers. Formal caregivers in residential care settings face different
      challenges when delivering care. OBJECTIVE: This study aimed at assessing the
      clinical correlates of challenging BPSD using the Chinese version of the
      Challenging Behaviour Scale (CCBS) designed for residential care settings.
      METHODS: One hundred and twenty-five participants were recruited from three care
      and-attention homes in Hong Kong. The CCBS was administered together with the
      Cantonese version of Mini-Mental State Examination (MMSE), Clinical Dementia
      Rating (CDR), Disability Assessment for Dementia (DAD) and Neuropsychiatric
      Inventory (NPI) to explore the relationships between challenging behaviour and
      important clinical correlates. RESULTS: The CCBS had good internal consistency
      (alpha = 0.86), inter-rater (ICC = 0.79) and test-retest reliability (ICC =
      0.98). A four-factor structure is demonstrated by factor analysis: hyperactivity
      behaviours, hypoactivity behaviours, verbally aggressive and aberrant behaviours.
      Challenging behaviours were associated with male gender, cognitive impairment,
      functional disability, neuropsychiatric symptoms, and higher caregiver's
      workload. CONCLUSIONS: The CCBS is a valid and reliable measure to assess BPSD in
      residential care settings in local Chinese community. It is useful in evaluating
      the challenges faced by formal caregivers during daily care of the dementia
      patients.

PMID- 16906633
TI  - Illness representations in early-stage dementia: a preliminary investigation.
AB  - BACKGROUND: The self-regulation model of adjustment to illness suggests that
      individual differences in coping and responding are related to the illness
      representations people hold. The present study explored the feasibility of
      applying this concept with people with early-stage dementia. METHOD:
      Understanding of the illness was explored in semi-structured interviews with 22
      people who had a diagnosis of mild to moderate Alzheimer's disease or mixed
      dementia, and a measure of mood was administered. Interview transcripts were
      subjected to content analysis. RESULTS: Representations covering illness
      identity, cause, course, cure/control and consequences were successfully
      elicited, but diverged from professional constructs in some important respects.
      Most participants regarded their difficulties as part of normal ageing, and one
      third viewed their condition as stable or improving. Almost all participants
      described some positive coping strategies; participants who believed that nothing
      could be done to help were more likely to score above clinical cut-offs for
      depression or anxiety. CONCLUSIONS: The findings offer a preliminary insight into
      the nature of illness representations in early-stage dementia, and support the
      relevance of the self-regulation model as a basis for understanding and
      intervention.

PMID- 16906634
TI  - Stress in caregivers of demented people in Korea--a modification of Pearlin and
      colleagues' stress model.
AB  - OBJECTIVES: We investigated the influence of demented people's function and
      caregiver burden on caregivers' psychological distress. Based on a modified model
      of Pearlin and colleagues (1990), we assessed the stress of demented people's
      caregivers in Korea. METHODS: A total of 122 demented people and their caregivers
      participated in this study. We evaluated dementia severity by the Clinical
      Dementia Rating (CDR), and caregivers reported their objective and subjective
      stressors. Objective stressors are the demented people's functional deterioration
      and behavioral problems, and subjective stressors are caregivers' reaction to
      objective stressors and the subjective burden in caregiving. The overall
      psychological distress of caregivers was evaluated by the Beck Depression
      Inventory (BDI) and the Spielberger Trait Anxiety Inventory-State (STAI-S).
      RESULTS: There were significant differences in both objective and subjective
      stressors according to the severity of dementia, but there was no significant
      difference in caregivers' psychological distress. The goodness-of-fit evaluation
      model showed the coping and social support variables affected the psychological
      distress as mediator variables (df = 109, chi (2) = 209.75, NFI = 0.949, RFI =
      0.929, IFI = 0.975, TLI = 0.964, RMSEA = 0.087). CONCLUSION: The model suggests
      that psychological distress of caregivers is related to diverse variables, such
      as objective and subjective stressors, coping, and social support. This study
      provides verification of the modified model of Pearlin and coworkers in Koreans,
      and lays a foundation for practical use and further study.

PMID- 16906635
TI  - Tumor angiogenesis assessed by three-dimensional power Doppler ultrasound in
      early, advanced and metastatic ovarian cancer: A preliminary study.
AB  - OBJECTIVE: To evaluate tumor vascularity by three-dimensional power Doppler
      ultrasound (3D-PDU) in early and advanced stage primary ovarian cancers and in
      metastatic tumors to the ovary. PATIENTS AND METHODS: This was a retrospective
      analysis of clinical and sonographic data from 49 women with primary ovarian
      cancers or metastatic tumors to the ovary. All women underwent 3D-PDU prior to
      surgery. Vascularization index (VI), flow index (FI) and vascularization flow
      index (VFI) from solid portions or papillary projections in the tumors were
      calculated using the Virtual Organ Computer-aided AnaLysis (VOCAL(trade mark))
      program. Definitive histological diagnosis was obtained in each case. RESULTS:
      Among the 49 women, 10 had stage I primary cancers (five low-malignant potential
      tumors and five invasive tumors), 26 had advanced stage primary ovarian cancers
      and 13 had metastatic tumors to the ovary. Mean VI and VFI were significantly
      higher in advanced stage tumors and metastatic tumors as compared with early
      stage tumors. No differences in 3D-PDU indices were found between advanced stage
      and metastatic cancers. CONCLUSIONS: Vascular indices derived from 3D-PDU tend to
      be higher in advanced stage and metastatic ovarian cancers as compared with early
      stage ovarian tumors.

PMID- 16906636
TI  - Studies on spasmogenic and spasmolytic activities of Calendula officinalis
      flowers.
AB  - The aqueous-ethanol extract of Calendula officinalis flowers (Co.Cr) was studied
      for its possible spasmolytic and spasmogenic effects in isolated gut
      preparations. In rabbit jejunum, Co.Cr caused a dose-dependent (0.03-3.0 mg/mL)
      relaxation of spontaneous and K+-induced contractions, suggestive of calcium
      channel blockade (CCB). In a few preparations, a mild non-reproducible
      spasmogenic effect was observed at lower doses, followed by relaxation. The CCB
      effect was confirmed when pretreatment of the jejunum preparations with Co.Cr
      produced a dose-dependent rightward shift in the Ca(++) dose-response curves,
      similar to that of verapamil. Activity-directed fractionation revealed that the
      spasmolytic activity of the plant was concentrated in its organic fractions. The
      aqueous fraction exhibited a marked atropine sensitive spasmogenic effect but was
      found to be devoid of any spasmolytic effect. These data indicate that the crude
      extract of Calendula officinalis flowers contains both spasmolytic and
      spasmogenic constituents, exhibiting these effects through calcium channel
      blocking and cholinergic activities and this study provides a scientific base for
      its traditional use in abdominal cramps and constipation.

PMID- 16906637
TI  - Anticomplement activity of cycloartane glycosides from the rhizome of Cimicifuga
      foetida.
AB  - A tetranor-cycloartane glycoside and two 9,19-cycloartane glycosides were
      isolated from the EtOAc-soluble fraction of the rhizome of Cimicifuga foetida.
      The structures of the compounds were determined to be cimilactone A (1), 25-O
      acetylcimigenol 3-O-beta-d-xylopyranoside (2) and cimigenol 3-O-alpha-l
      arabinopyranoside (3), respectively, using spectroscopic analysis. The three
      compounds were examined for their anticomplement activity against the classical
      pathway of the complement system. Compound 1 showed significant anticomplement
      activity with an IC(50) value of 28.6 microm, whereas compounds 2 and 3 were
      inactive.

PMID- 16906638
TI  - Antiplasmodial activity of Homalium letestui.
AB  - The in vivo antiplasmodial activity of the ethanol root extract of Homalium
      letestui used as a malaria remedy in Southern Nigeria was evaluated in Plasmodium
      berghei berghei infected mice. Homalium letestui root extract (500-1000
      mg/kg/day) exhibited significant (p < 0.05) blood schizontocidal activities both
      in a 4-day early infection test and in an established infection with a
      considerable mean survival time comparable to that of the standard drug,
      chloroquine, 5 mg/kg/day. The root extract possesses significant (p < 0.05)
      antiplasmodial activity, which can be exploited in malaria therapy.

PMID- 16906639
TI  - Stimulatory effects of extract prepared from the bark of Cinnamomum cassia blume
      on the function of osteoblastic MC3T3-E1 cells.
AB  - The ethanol extract from the bark of Cinnamomum cassia Blume (CCE) was tested for
      estrogenic activity. CCE (4-60 microg/mL) significantly induced the growth of MCF
      7 cells, an ER-positive human breast cancer cell line, over that of untreated
      control cells (p < 0.05). In the ER competitive binding assay, CCE showed higher
      affinity with ERbeta compared with ERalpha. To investigate the bioactivities of
      CCE, which act on bone metabolism, the effects of CCE on the function of
      osteoblastic MC3T3-E1 cells and the production of local factors in osteoblasts
      were studied. CCE (4-60 microg/mL) dose-dependently increased the survival of
      MC3T3-E1 cells. In addition, CCE (10 and 50 microg/mL) increased alkaline
      phosphatase (ALP) activity, collagen synthesis and osteocalcin secretion in MC3T3
      E1 cells. Treatment with CCE (10 and 50 microg/mL) prevented apoptosis induced by
      TNF-alpha (10(-10) m) in osteoblastic cells. In the presence of TNF-alpha,
      culture with CCE (10-100 microg/mL) for 48 h inhibited the production of IL-6 and
      nitric oxide in osteoblastic MC3T3-E1 cells. These results suggest that
      Cinnamomum cassia has a direct stimulatory effect on bone formation in vitro and
      may contribute to the prevention of osteoporosis and inflammatory bone diseases.

PMID- 16906640
TI  - Correlation between the in vitro antioxidant activity and polyphenol content of
      aqueous extracts from Bulgarian herbs.
AB  - The water phase antioxidant activity of extracts from 23 Bulgarian medicinal
      plants was studied in relation to their polyphenol content in comparison with
      mate, black tea, honeybush and rooibos foreign species. Antioxidant activity was
      measured by the ABTS (2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid))
      cation radical decolorization assay, and the total polyphenol content was assayed
      according to the Folin-Ciocalteu method. Five Bulgarian plant extracts exhibited
      higher antioxidant activity than that of mate, which is 21.7% of all Bulgarian
      herbs included in this study. These were Alchemilla vulgaris L. (4.79 +/- 0.14
      mm), Sambucus ebulus L. (4.03 +/- 0.07 mm), Mentha spicata L. (3.90 +/- 0.03 mm),
      Fragaria vesca L. (3.74 +/- 0.06 mm), Crataegus monogyna Jacq. (3.63 +/- 0.05
      mm). Another eight Bulgarian medicinal plant extracts exhibited an intermediate
      antioxidant activity - lower than that of mate and higher than that of honeybush,
      which makes 34.8% of all Bulgarian herbs included in the study. More than half of
      the herbal extracts included in the present study exhibited antioxidant activity
      higher than or comparable to the reference foreign plants. A positive correlation
      (r = 0.92) between antioxidant activity and polyphenol content was found,
      suggesting that the antioxidant capacity of the aqueous plant extracts is due to
      a great extent to their polyphenols.

PMID- 16906641
TI  - Miconazole gel compared with Zataria multiflora Boiss. gel in the treatment of
      denture stomatitis.
AB  - An open, randomized, controlled study with two parallel treatment groups was done
      to evaluate the efficacy of a miconazole 2% gel compared with Zataria multiflora
      0.1% gel applied four times daily for 2 weeks, in the treatment of Candida
      associated denture stomatitis. Twenty four patients were included in the study.
      The efficacy variables were the colony count of Candida from the palatal mucosa
      and the denture surface and the erythema surface of the palatal mucosa on days 0,
      7, 14, 21 and 28 after commencement of therapy. Twelve patients received
      miconazole gel and twelve Z. multiflora gel. The erythema surface was
      significantly reduced by both gels. No significant difference was seen between
      the two groups (p < 0.05). There was a significant reduction in the colony count
      of the palatal mucosa in both groups (except on days 21 and 28 in the Zataria
      group p = 0.07 and 0.08). Miconazole treatment reduced the number of denture
      colonies more efficiently than Z. multiflora except for day 21 when the efficacy
      of both groups was similar (p = 0.17). The results indicate that Z. multiflora
      gel reduced the surface erythema of the palate more efficiently than miconazole
      gel but did not reduce the colony count of the denture surface as efficiently as
      miconazole.

PMID- 16906642
TI  - Evaluation of oriental medicinal herbs for estrogenic and antiproliferative
      activities.
AB  - Herb extracts commercially used in Asia were screened for their estrogenic
      activity with a recombinant yeast system with both a human estrogen receptor (ER)
      expression plasmid and a reporter plasmid. Pueraria lobata (flower) had the
      highest estrogenic relative potency (RP, 17-estradiol = 1.00) (7.8e-3) (RP for +
      control), followed by Amomum xanthioides (1.3e-3), Glycyrrhiza uralensis,
      Zingiber officinale, Rheum palmatum, Curcuma aromatica, Eriobotrya japonica,
      Sophora flavescens, Anemarrhena asphodeloides, Polygonum multiflorum and Pueraria
      lobata (root) (9.5e-4-1.0e-4), and Prunus persica, Lycoppus lucidus and
      Adenophora stricta (9.0e-5-8.0e-5). In the antiproliferative assay, five human
      cancer cell lines representing different tissues (breast, lung and ovary) were
      used. Eriobotrya japonica showed strong cytotoxicity in ER-negative breast cancer
      (MDA-MB-231), cervix epitheloid (HeLa) and lung (A549) carcinoma cell lines.

PMID- 16906643
TI  - The hand and the ipsilateral primary somatosensory cortex.

PMID- 16906644
TI  - Inhaled corticosteroids and children.

PMID- 16906645
TI  - A spotlight on the searchlight.

PMID- 16906646
TI  - Imatinib and altered bone and mineral metabolism.

PMID- 16906647
TI  - Arctic hydrology during global warming at the Palaeocene/Eocene thermal maximum.
AB  - The Palaeocene/Eocene thermal maximum represents a period of rapid, extreme
      global warming 55 million years ago, superimposed on an already warm world. This
      warming is associated with a severe shoaling of the ocean calcite compensation
      depth and a >2.5 per mil negative carbon isotope excursion in marine and soil
      carbonates. Together these observations indicate a massive release of 13C
      depleted carbon and greenhouse-gas-induced warming. Recently, sediments were
      recovered from the central Arctic Ocean, providing the first opportunity to
      evaluate the environmental response at the North Pole at this time. Here we
      present stable hydrogen and carbon isotope measurements of terrestrial-plant- and
      aquatic-derived n-alkanes that record changes in hydrology, including surface
      water salinity and precipitation, and the global carbon cycle. Hydrogen isotope
      records are interpreted as documenting decreased rainout during moisture
      transport from lower latitudes and increased moisture delivery to the Arctic at
      the onset of the Palaeocene/Eocene thermal maximum, consistent with predictions
      of poleward storm track migrations during global warming. The terrestrial-plant
      carbon isotope excursion (about -4.5 to -6 per mil) is substantially larger than
      those of marine carbonates. Previously, this offset was explained by the
      physiological response of plants to increases in surface humidity. But this
      mechanism is not an effective explanation in this wet Arctic setting, leading us
      to hypothesize that the true magnitude of the excursion--and associated carbon
      input--was greater than originally surmised. Greater carbon release and strong
      hydrological cycle feedbacks may help explain the maintenance of this
      unprecedented warmth.

PMID- 16906648
TI  - The ethics of influenza vaccination.

PMID- 16906649
TI  - The ethics of influenza vaccination.

PMID- 16906651
TI  - Bibliography. Current awareness in prenatal diagnosis.

PMID- 16906650
TI  - Down-regulated VEGF expression in the diabetic heart is normalized by an
      endothelin ETA receptor antagonist.
AB  - Recently, down-regulation of vascular endothelial growth factor (VEGF) in the
      heart was suggested as a potential molecular explanation for the increased risk
      of cardiovascular morbidity and mortality in patients with diabetes. Increased
      endothelin-1 production is reported in diabetes. Here, we report that down
      regulated VEGF expression in the diabetic rat heart is normalized by an
      endothelin ETA receptor antagonist, suggesting that endothelin antagonism may be
      a novel therapeutic strategy for diabetic heart.

PMID- 16906652
TI  - Treatment of oral, facial, and head pain.

PMID- 16906653
TI  - New treatment for chest pain.

PMID- 16906654
TI  - Reducing risk of entrapment in hospital beds.

PMID- 16906655
TI  - Stronger warning for antibiotic Tequin.

PMID- 16906657
TI  - Human tissue products recalled.

PMID- 16906656
TI  - New targeted therapy for rare stomach, kidney cancers.

PMID- 16906658
TI  - Another option for fungal infections.

PMID- 16906659
TI  - New drug for chronic constipation.

PMID- 16906660
TI  - Making multiple lifestyle changes can lower high blood pressure.

PMID- 16906661
TI  - Ensuring the safety of medical devices.

PMID- 16906662
TI  - Online version of 'My Family Health Portrait' available in English and Spanish.
AB  - A revised and more convenient computer tool is available without cost, in English
      and Spanish, to help families gather their health information.

PMID- 16906664
TI  - Treating restless legs syndrome.

PMID- 16906663
TI  - Prostate health: what every man needs to know.

PMID- 16906665
TI  - The FDA and product recalls.

PMID- 16906666
TI  - New health initiatives to improve cancer treatments.

PMID- 16906667
TI  - Keeping up with drug safety information.

PMID- 16906668
TI  - FDA approval: darunavir.

PMID- 16906669
TI  - New black box warning for ritonavir-boosted tipranavir.

PMID- 16906670
TI  - Uncertain future for early access?

PMID- 16906671
TI  - The down side of expanded open access programs. A site management perspective.

PMID- 16906673
TI  - Universal access to ARVs requires stronger health systems.

PMID- 16906672
TI  - The role of IRBs in U.S. HIV clinical trials.

PMID- 16906674
TI  - Reports from the 7th HIV Pharmacology Workshop.

PMID- 16906675
TI  - Cobalt in hard metals and cobalt sulfate, gallium arsenide, indium phosphide and
      vanadium pentoxide.

PMID- 16906676
TI  - [CR image-processing technology in a chest domain].

PMID- 16906678
TI  - [Development of clinical application techniques for the direct FPD digital
      radiographic system].

PMID- 16906677
TI  - [Introduction to PCM technology].

PMID- 16906679
TI  - [64-channel MDCT cardiovascular imaging].

PMID- 16906680
TI  - [Multi-slice CT of the extremities].

PMID- 16906681
TI  - [Magnetic resonance (MR) imaging of joints: method and interpretation of
      radiogram point].

PMID- 16906682
TI  - [Advantages and disadvantages of 3T-MRI body applications].

PMID- 16906683
TI  - [Development of standardization in EHR using IHE integration profiles].

PMID- 16906684
TI  - Our conflicted medical journals.

PMID- 16906685
TI  - Tough-talking journal editor faces accusations of leniency.

PMID- 16906686
TI  - A pox on stem cell research.

PMID- 16906687
TI  - Patients with rare diseases work to jump-start research; advocacy groups create
      their own tissue banks to aid in drug treatment.

PMID- 16906688
TI  - FDA to weigh test of blood substitute out of public view.

PMID- 16906690
TI  - Fight intensifies over who acts for children; judge lets teen waive usual cancer
      care; trial set for August.

PMID- 16906689
TI  - Biopure moves to sell blood substitute in Europe.

PMID- 16906691
TI  - Medicine, Peace and Public Policy.

PMID- 16906692
TI  - Vision Sciences Society Meeting, May 6-11, 2005, Sarasota, Florida, USA.
      Abstracts.

PMID- 16906693
TI  - Fall Vision Meeting, October 21-23, 2005, Tuscon, Arizona, USA. Abstracts.

PMID- 16906694
TI  - Vision Sciences Society Meeting, May 5-10, 2006, Sarasota, Florida, USA.
      Abstracts.

PMID- 16906695
TI  - Bibliography. Current world literature. Refractive surgery.

PMID- 16906696
TI  - Brijini Archipelago: story of Kupelwieser, Koch and cultivation of 14 islands.

PMID- 16906697
TI  - Prognostic factors in the occurrence of posttraumatic epilepsy after penetrating
      head injury suffered during military service.
AB  - In this retrospective study, the authors evaluated confounding risk factors,
      which are allegedly influential in causing unprovoked posttraumatic epilepsy, in
      489 patients from the frontlines of the Iran-Iraq War. Four hundred eighty-nine
      patients were followed for 6 to154 months (mean 39.4 months, median 23 months),
      and important factors precipitating posttraumatic epilepsy were evaluated using
      uni- and multivariate regression analysis. One hundred fifty-seven (32%) of 489
      patients became epileptic during the study period. The results of univariate
      analysis indicated a significant relationship between epilepsy and Glasgow
      Outcome Scale (GOS) score (X2 = 76.49, p < 0.0001, df = 2), Glasgow Coma Scale
      score at admission (X2 = 19.48, p < 0.0001, df = 3), motor deficit (X2 = 11.79, p
      < 0.001, df = 1), mode of injury (X2 = 10.731, p < 0.05), transventricular injury
      (X2 = 6.9, p < 0.008, df = 1), dysphasia (X2 = 5.3, p < 0.02), central nervous
      system infections (X2 = 5.3, p < 0.02), and early-onset seizures (X2 = 4.1, p <
      0.04, df = 1). The results of multivariate analysis, on the other hand, indicated
      that the GOS score and motor deficit were of greater statistical importance (X2 =
      35.24, p < 0.0001; and X2 = 7.1, p < 0.07, respectively). Factors that did have
      much statistically significant bearing on posttraumatic epilepsy were the
      projectile type, site of injury on the skull, patient age, number of affected
      lobes, related hemorrhagic complications, and retained metallic or bone
      fragments. Glasgow Outcome Scale score and focal motor neurological deficit are
      of particular importance in predicting posttraumatic epilepsy after missile head
      injury.

PMID- 16906698
TI  - Outcome prediction following penetrating craniocerebral injury in a civilian
      population: aggressive surgical management in patients with admission Glasgow
      Coma Scale scores of 6 to 15.
AB  - In an attempt to assess admission Glasgow Coma Scale (GCS) scores and other
      radiographic variables after penetrating craniocerebral injury in relationship to
      outcome, the author evaluated a series of 294 patients with penetrating injuries
      who presented with a GCS score of 6 to 15 over a 6-year period. Entrance criteria
      required a replicable neurological examination that was not altered by the
      presence of hypotension, drugs/toxins, or systemic injury. All patients underwent
      surgical intervention and aggressive perioperative management, including
      resuscitative protocols, in the neurosurgical intensive care unit. The author
      previously devised prospective models of outcome remained unchanged in this
      series. The variables most predictive of death include admission GCS score and
      subarachnoid hemorrhage in one model and admission GCS score and pupillary
      changes in a second when pupillary response was definitive at admission (p < or =
      0.00005). Other important variables related to morbidity include admission GCS,
      bihemispheric injury when associated with intraventricular hemorrhage, and
      diffuse fragmentation (p < or = 0.001). In this study a significant relationship
      between operative intervention and survival (p < or = 0.01) was found in patients
      with an admission GCS scores of 6 to 8. No significant relationships between
      operative intervention and survival were found in patients with admission GCS
      scores of 9 to 12 and 13 to 15. A significant relationship between operative
      intervention and morbidity (p < or = 0.01) was also demonstrated in patients with
      an admission GCS score of 12 to 15. No significant relationships between
      operative intervention and morbidity were found in patients with an admission GCS
      score of 6 to 8 and 9 to 12.

PMID- 16906699
TI  - Analysis of pediatric head injury from falls.
AB  - The authors conducted a study to describe the incidence and types of fall-related
      head injury observed at a pediatric trauma center. We performed a retrospective
      analysis of all patients under 15 years of age treated for fall-related trauma
      between 1992 and 1998. Falls were classified as low (< 15 feet) and high level (>
      or = 15 feet). Seven hundred twenty-nine cases were identified with a mortality
      rate of 1.7%. A fall of greater than 15 feet (high-level fall) was associated
      with a higher mortality rate than low-level falls (2.4% compared with 1.0%,
      respectively). Ninety-eight patients had sustained a calvarial fracture and 93
      experienced a basal skull fracture. Twenty-six patients had suffered a cerebral
      contusion, 25 a subarachnoid hemorrhage, 22 a subdural hematoma, and 12 had an
      epidural hematoma. Forty-nine patients required surgery for traumatic injuries;
      of these, 10 underwent craniotomy for evacuation of a blood clot. Height was not
      predictive of the Glasgow Coma Scale (GCS) score. In all four deaths resulting
      from a low-level fall there was an admission GCS score of 3, and abnormal
      findings were demonstrated on computerized tomography scanning. Death from high
      level falls was attributable to either intracranial injuries (50%) or severe
      extracranial injuries (50%). Intracranial injury is the major source of fall
      related death in children and, unlike extracranial insults, brain injuries are
      sustained with equal frequency from low- and high-level falls in this population.
      The only cause of mortality from low-level falls was intracranial injury. Trauma
      triage criteria must account for these differences in the pediatric population.

PMID- 16906700
TI  - Traumatic intracranial aneurysms.
AB  - Traumatic intracranial aneurysms are rare, occurring in fewer than 1% of patients
      with cerebral aneurysms. They can occur following blunt or penetrating head
      trauma and are more common in the pediatric population. Traumatic aneurysms can
      be categorized histologically as true, false, or mixed, with false aneurysms
      being the most common. These aneurysms can present in a variety of ways, but are
      typically associated with an acute episode of delayed intracranial hemorrhage
      with an average time from initial trauma to aneurysm hemorrhage of approximately
      21 days. The mortality rate for patients harboring these aneurysms may be as high
      as 50%. Prompt diagnosis based on arteriography and aggressive surgical
      management are associated with better outcome than conservative treatment. The
      authors describe a classification scheme for traumatic aneurysms based on their
      anatomical location and conclude that 1) posttraumatic aneurysm must be
      considered in patients with acute neurological deterioration following closed
      head injury; 2) they can occur following mild closed head injury; 3) they occur
      more commonly in children than in adults; and 4) surgical clipping and/or
      endovascular occlusion is the definitive treatment.

PMID- 16906701
TI  - The independent effect of gender on outcomes following traumatic brain injury: a
      preliminary investigation.
AB  - Although epidemiological studies of gender differences in outcome after brain
      injury are limited, studies in animals indicate higher fatality rates for
      females. Studies in which healthy human brain metabolism was investigated also
      suggest gender differences. In this paper the authors examine gender as an
      independent predictor of survival following brain injury. A prospective cohort of
      severely and moderately brain injured individuals was identified from two trauma
      centers over a period of 3.5 years. Patients enrolled in the cohort were followed
      for as long as 18 months postdischarge. The Glasgow Outcome Scale was used to
      measure long-term outcome. Overall, mortality was 1.28 times higher in females
      than males, with the greatest difference of 2.14 found in deaths postdischarge.
      Controlling for age, admission Glasgow Coma Score, penetrating as compared with
      blunt injury, and the presence of multiple trauma, females were 1.75 times more
      likely than males to die of their brain injury (95% confidence interval 1.09
      2.82). Furthermore, females were 1.57 times more likely to experience poor
      outcomes (that is, severe disability or persistent vegetative state) than males.
      These findings suggest the need to examine similar effects in different cohorts
      and to identify the pathophysiological basis for the differences observed in this
      epidemiological study.

PMID- 16906702
TI  - Are steroids really ineffective for severely head injured patients?
AB  - The "Guidelines for the Management of Severe Head Injury" states that the use of
      glucocorticoids is not recommended for improving morbidity outcome. Conversely,
      the "National Acute Spinal Cord Injury Study" (NASCIS) in the United States
      concluded that treatment with very high doses of methylprednisolone (30 mg/kg) is
      indicated for acute spinal cord trauma. In this paper the author will discuss the
      reasons for this great discrepancy between head injuries and spinal cord traumas.
      A 30-mg dose of methylprednisolone was used as a bolus dose in the spinal cord
      study to inhibit oxygen free radical-induced lipid peroxidation. In most of the
      papers cited containing Class I data on severe head injury studies the
      investigators used smaller doses of glucocorticoids as compared with those in the
      spinal cord study. Moreover, some of the papers included cases in which the time
      from insult to the initiation of treatment had been poorly controlled. Therefore,
      based on previous papers, it is appropriate to relinquish megadose steroid
      therapy for head injury patients. A good prospective multicenter trial of high
      dose methylprednisolone for traumatic brain injury should be considered in which
      dosage and timing parameters similar to those enacted for the NASCIS studies are
      used.

PMID- 16906703
TI  - Evaluating the outcome of severe head injury with transcranial Doppler
      ultrasonography.
AB  - The authors conducted a study to determine the value of transcranial Doppler
      (TCD) ultrasonography in evaluating the outcome of severely head injured patients
      and to correlate the TCD values with those obtained from intracranial pressure
      (ICP) and cerebral perfusion pressure (CPP) monitoring. The authors conducted a
      prospective study of 125 patients with severe head injury (Glascow Coma Scale
      scores of less than 9) who underwent TCD ultrasonography according to the
      standard technique of insonating the middle cerebral artery (MCA) and measuring
      the mean blood flow velocity and pulsatility index within the first 24 hours of
      admission. The ICP and CPP values, as well as other clinical, analytical, and
      neuroimaging data, were also recorded. After 6 months, outcome was evaluated
      using the Glasgow Outcome Scale. Moderate disability and complete recovery were
      considered "good" outcome; death, vegetative state, and severe disability were
      considered "poor." In 67 patients (54%) good outcome was demonstrated whereas in
      58 (46%) it was poor. The mean blood flow velocity of the MCA in patients with
      good outcome was 44 cm/second; in those with poor outcomes it was 36 cm/second (p
      < 0.003). The mean PI in cases of good outcome was 1 whereas in poor outcome was
      1.56 (p < 0.0001). The correlations of ICP and CPP to PI were statistically
      significant (r2 = 0.6; p < 0.0001). When performed in the first 24 hours of
      severe head injury, TCD ultrasonography is valid in predicting the patient's
      outcome at 6 months and correlates significantly with ICP and CPP values.

PMID- 16906704
TI  - Mesoporous silica beads embedded with semiconductor quantum dots and iron oxide
      nanocrystals: dual-function microcarriers for optical encoding and magnetic
      separation.
AB  - Mesoporous beads are promising materials for embedding functional nanoparticles
      because of their nanometer-sized pores and large surface areas. Here we report
      the development of silica microbeads embedded with both semiconductor quantum
      dots (QD) and iron oxide (Fe3O4) nanocrystals as a new class of dual-function
      carriers for optical encoding and magnetic separation. The embedding (doping)
      process is carried out by either simultaneous or sequential addition of quantum
      dots and iron oxide (Fe3O4) nanocrystals in solution. The doping process is fast
      and quantitative, but the incorporated iron oxide strongly attenuates the signal
      intensity of QD fluorescence. We find that this attenuation is not due to
      conventional fluorescence quenching but is caused by the broad optical absorption
      spectrum of mixed-valence Fe3O4. For improved biocompatibility and reduced
      nonspecific binding, the encoded beads are further coated with amphiphilic
      polymers such as octylamine poly(acrylic acid). The results indicate that the
      polymer-coated beads are well suited for target capturing and enrichment,
      yielding magnetic separation efficiencies higher than 99%. By combining the
      multiplexing capability of QDs with the superparamagnetic properties of iron
      oxide nanocrystals, this class of encoded beads is expected to find broad
      applications in high-throughput and multiplexed biomolecular assays.

PMID- 16906705
TI  - Chemical sensors based on micromachined transducers with integrated
      piezoresistive readout.
AB  - We demonstrate an approach for the development of chemical sensors utilizing
      silicon micromachined physical transducers with integrated piezoresistive
      readout. Originally, these transducers were developed and optimized as sensitive
      accelerometers for automotive applications. However, by applying a chemically
      responsive layer onto the transducer, we convert these transducers into chemical
      sensors. These transducers are attractive for chemical sensing applications for
      several key reasons. First, the required sensitivity of the chemical sensor can
      be achieved by choosing the right spring constant of the transducer. Second, the
      integrated piezoresistive readout of the transducer is already optimized and is
      very straightforward, providing a desired reproducibility in measurements, while
      not requiring bulky equipment. Third, chemically responsive film deposition is
      simple due to the ease of access to the transducer's surface. Fourth, such
      transducers are already available for another (automotive) application, making
      these sensors very cost-effective. The applicability of this approach is
      illustrated by the fabrication of highly sensitive CO2 sensors. To study
      hysteresis effects, we selected high CO2 concentrations (10-100% CO2) to provide
      the worst-case scenario for the sensor operation. These sensors demonstrate a
      hysteresis-free performance over the concentration range from 10 to 100% vol CO2,
      have detection limits of 160-370 ppm of CO2, and exhibit a relatively rapid
      response time, T(90) = 45 s. Importantly, we demonstrate a simple method for
      cancellation of vibration effects when these physical transducers, initially
      developed as accelerometers, are applied as chemical sensors.

PMID- 16906706
TI  - Ultrafast gas chromatography on single-wall carbon nanotube stationary phases in
      microfabricated channels.
AB  - The key to rapid temperature programmed separations with gas chromatography are a
      fast, low-volume injection and a short microbore separation column with fast
      resistive heating. One of the major problems with the reduction of column
      dimensions for micro gas chromatography is the availability of a stationary phase
      that provides good separation performance. In this report, we present the first
      integration of single-wall carbon nanotubes (SWNTs) as a stationary phase into
      100 mum x 100 mum square and 50-cm-long microfabricated channels. The small size
      of this column with integrated resistive heater and the robustness of the SWNT
      phase allow for fast temperature programming of up to 60 degrees C/s. A
      combination of the fast temperature programming and the narrow peak width of
      small-volume injections that can be obtained from a high-speed, dual-valve
      injection system allows for rapid separations of gas mixtures. We demonstrate
      highly reproducible separations of four-compound test mixtures on these columns
      in less than 1 s using fast temperature programming.

PMID- 16906707
TI  - Controlling the color space response of colorimetric luminescent oxygen sensors.
AB  - The color space response of colorimetric luminescent oxygen sensors is described
      in terms of the Commission Internationale de l'Eclairage (CIE) x,y color
      coordinates. We show how the color change response to oxygen can be obtained,
      provided the quenching kinetics for all lumophores involved can be represented
      mathematically. The theory is illustrated by analysis of examples of theoretical
      sensors in which lumophores are quenched by Stern-Volmer kinetics to give red to
      green, green to red, and red to green to blue color responses as the partial
      pressure of oxygen is increased. The effects of lumophore emission lifetime and
      the permeability of the polymer matrix to oxygen are discussed in terms of the
      control of sensor response, which variations in these parameters offer.

PMID- 16906708
TI  - High-throughput and high-resolution flow cytometry in molded microfluidic
      devices.
AB  - We describe the design, fabrication, and operation of two types of flow
      cytometers based on microfluidic devices made of a single cast of
      poly(dimethylsiloxane). The stream of particles or cells injected into the
      devices is hydrodynamically focused in both transverse and lateral directions,
      has a uniform velocity, and has adjustable diameter and shape. The cytometry
      system built around the first microfluidic device has fluorescence detection
      accuracy comparable with that of a commercial flow cytometer and can analyze as
      many as 17 000 particles/s. This high-throughput microfluidic device could be
      used in inexpensive stand-alone cytometers or as a part of integrated
      microanalysis systems. In the second device, a stream of particles is focused to
      a flow layer of a submicrometer thickness that allows imaging the particles with
      a high numerical aperture microscope objective. To take long-exposure, low-light
      fluorescence images of live cells, the device is placed on a moving stage, which
      accurately balances the translational motion of particles in the flow. The
      achieved resolution is comparable to that of still micrographs. This high
      resolution device could be used for analysis of morphology and fluorescence
      distribution in cells in continuous flow.

PMID- 16906709
TI  - Holographic lactate sensor.
AB  - Measurement of blood l-lactate is used to assess and monitor exercise performance
      in sports medicine. This report describes the initial development of a
      holographic sensor, which employs a synthetic receptor, to enable the selective
      and continuous real-time measurement of l-lactate for eventual in vivo
      application. Three boronic acid-based receptors have been synthesized, integrated
      into thin acrylamide hydrogel films, and then subsequently transformed into
      holographic sensors. Changes in the replay wavelength of the sensors were used to
      characterize the swelling behavior of the matrix as a function of l-lactate
      concentration. It was found that the incorporation of 3-acrylamidophenyl boronic
      acid into an acrylamide hydrogel produced the largest response toward l-lactate.
      The effects of hydrogel composition, fluctuating l-lactate concentrations, and
      the response of potential interfering agents to the sensor have been
      investigated.

PMID- 16906711
TI  - Analysis of peptide MS/MS spectra from large-scale proteomics experiments using
      spectrum libraries.
AB  - A widespread proteomics procedure for characterizing a complex mixture of
      proteins combines tandem mass spectrometry and database search software to yield
      mass spectra with identified peptide sequences. The same peptides are often
      detected in multiple experiments, and once they have been identified, the
      respective spectra can be used for future identifications. We present a method
      for collecting previously identified tandem mass spectra into a reference library
      that is used to identify new spectra. Query spectra are compared to references in
      the library to find the ones that are most similar. A dot product metric is used
      to measure the degree of similarity. With our largest library, the search of a
      query set finds 91% of the spectrum identifications and 93.7% of the protein
      identifications that could be made with a SEQUEST database search. A second
      experiment demonstrates that queries acquired on an LCQ ion trap mass
      spectrometer can be identified with a library of references acquired on an LTQ
      ion trap mass spectrometer. The dot product similarity score provides good
      separation of correct and incorrect identifications.

PMID- 16906710
TI  - Sequence-specific, electronic detection of oligonucleotides in blood, soil, and
      foodstuffs with the reagentless, reusable E-DNA sensor.
AB  - The ability to detect specific oligonucleotides in complex, contaminant-ridden
      samples, without the use of exogenous reagents and using a reusable, fully
      electronic platform could revolutionize the detection of pathogens in the clinic
      and in the field. Here, we characterize a label-free, electronic sensor, termed E
      DNA, for its ability to simultaneously meet these challenging demands. We find
      that because signal generation is coupled to a hybridization-linked
      conformational change, rather than to only adsorption to the sensor surface, E
      DNA is selective enough to detect oligonucleotides in complex, multicomponent
      samples, such as blood serum and soil. Moreover, E-DNA signaling is monotonically
      related to target complementarity, allowing the sensor to discriminate between
      mismatched targets: we readily detect the complementary 17-base target against a
      50 000-fold excess of genomic DNA, can distinguish a three-base mismatch from
      perfect target directly in blood serum, and under ideal conditions, observe
      statistically significant differences between single-base mismatches. Finally,
      because the sensing components are linked to the electrode surface, E-DNA is
      reusable: a 30-s room temperature wash recovers >99% of the sensor signal. This
      work further supports the utility of E-DNA as a rapid, specific, and convenient
      method for the detection of DNA and RNA sequences.

PMID- 16906712
TI  - Capillary electrophoresis absorption detection using fiber-loop ring-down
      spectroscopy.
AB  - The application of phase-shift, fiber-loop, ring-down spectroscopy (PS-FLRDS) as
      an on-line detector for capillary electrophoresis (CE) of biomolecules is
      demonstrated. CE was conducted using a custom-designed capillary/fiber interface
      coupled to an absorption detector, which is based on the ring-down of an optical
      signal in a closed fiber waveguide loop. The ring-down times were obtained by
      measuring the phase difference between intensity modulated light entering and
      exiting the fiber loop. The incorporation of a microlens to enhance transmission
      through the sample gap led to an improvement of the sensitivity by up to 80%
      compared to the square-cut fiber and a reduction in the detection limit. The
      performance of the PS-FLRDS absorption technique as an online detector was
      characterized by flow injection through a capillary. Good repeatability and
      linear response were obtained, and the detection limit using the lensed
      fiber/capillary interface system was determined to be alpha(min) = 1.6 cm(-1) for
      an absorption path of approximately 30 microm. PS-FLRDS coupled to CE was also
      applied to the analysis of human serum albumin (HSA) by using a NIR dye as a
      noncovalent label. The excess free dye and the dye/protein complex were resolved.
      The labeling coefficient was determined to be approximately 6, and good
      repeatability of peak areas (RSD = 8.7%) was obtained for the analysis of HSA.
      Furthermore, an excellent linear response (R2 > 0.99) was obtained between the
      peak areas and concentrations of HSA. The detection limit of labeled HSA was
      determined to be 1.67 microM.

PMID- 16906713
TI  - Roles of metal ion complexation and membrane permeability in the metal flux
      through lipophilic membranes. Labile complexes at permeation liquid membranes.
AB  - The various physicochemical factors that influence the flux of carrier
      transported metal ions through permeation liquid membranes (PLM) are studied
      systematically. Understanding PLM behavior is important (i) to optimize the
      application of PLM as metal speciation sensors in environmental media and (ii)
      because PLM may serve as bioanalogical devices that help to elucidate the
      environmental physicochemical processes occurring at the surface of biological
      membranes. Diffusion of free and complexed metal ions in solution, as well as
      diffusion of the metal carrier complex in the membrane, is considered. The
      respective roles of diffusion layer thickness, ligand concentration, complex
      stability, carrier concentration, and membrane thickness are studied
      experimentally in detail and compared with theory, using various labile
      complexes, namely, Pb(II)-diglycolate, Cu(II)-diglycolate, and Cu(II)-N-(2
      carboxyphenyl)glycine. Conditions where either membrane diffusion or solution
      diffusion is rate limiting are clearly discriminated. It is shown in particular,
      that, by tuning the carrier concentration or membrane thickness, either the free
      metal ion concentration or the total labile metal species are measured. PLM can
      thus be used to determine whether models based on the free ion activity in
      solution (such as BLM or FIAM models) are applicable to metal uptake by
      microorganisms in a real natural medium.

PMID- 16906714
TI  - Microchip-based macroporous silica sol-gel monolith for efficient isolation of
      DNA from clinical samples.
AB  - Effective microchip extraction of deoxyribonucleic acid (DNA) from crude
      biological matrixes has been demonstrated using silica beads or hybrid phases
      composed of beads and sol-gel. However, the use of monolithic sol-gels alone for
      extraction of human genomic DNA has been more difficult to define. Here we
      describe, for the first time, the successful use of monolithic tetramethyl
      orthosilicate-based sol-gels for effective micro-solid-phase extraction (muSPE)
      of DNA in a glass microchip format. A functional monolithic silica phase with
      micrometer-scale pores in the silica matrix resulted from addition of
      poly(ethylene glycol), a poragen, to the precursor mixture. This allowed a
      monolithic sol-gel bed to be established in a microchip channel that provided
      large surface area for DNA extraction with little flow-induced back pressure. DNA
      extraction efficiencies for simple systems (lambda-phage DNA) were approximately
      85%, while efficiencies for the reproducible extraction of human genomic DNA from
      complex biological matrixes (human blood) were approximately 70%. Blockage of the
      sol-gel pores by components in the lysed blood was observed in repeat extraction
      on a single device as a decrease in the extraction efficiency. The developed
      muSPE protocol was further evaluated to show applicability to clinical samples
      and bacterial cultures, through extraction of PCR-amplifiable DNA.

PMID- 16906715
TI  - Quantitative determination of absolute organohalogen concentrations in
      environmental samples by X-ray absorption spectroscopy.
AB  - An in situ procedure for quantifying total organic and inorganic Cl
      concentrations in environmental samples based on X-ray absorption near-edge
      structure (XANES) spectroscopy has been developed. Cl 1s XANES spectra reflect
      contributions from all Cl species present in a sample, providing a definitive
      measure of total Cl concentration in chemically heterogeneous samples. Spectral
      features near the Cl K-absorption edge provide detailed information about the
      bonding state of Cl, whereas the absolute fluorescence intensity of the spectra
      is directly proportional to total Cl concentration, allowing for simultaneous
      determination of Cl speciation and concentration in plant, soil, and natural
      water samples. Absolute Cl concentrations are obtained from Cl 1s XANES spectra
      using a series of Cl standards in a matrix of uniform bulk density. With the high
      sensitivity of synchrotron-based X-ray absorption spectroscopy, Cl concentration
      can be reliably measured down to the 5-10 ppm range in solid and liquid samples.
      Referencing the characteristic near-edge features of Cl in various model
      compounds, we can distinguish between inorganic chloride (Cl(inorg)) and
      organochlorine (Cl(org)), as well as between aliphatic Cl(org) and aromatic
      Cl(org), with uncertainties in the range of approximately 6%. In addition, total
      organic and inorganic Br concentrations in sediment samples are quantified using
      a combination of Br 1s XANES and X-ray fluorescence (XRF) spectroscopy. Br
      concentration is detected down to approximately 1 ppm by XRF, and Br 1s XANES
      spectra allow quantification of the Br(inorg) and Br(org) fractions. These
      procedures provide nondestructive, element-specific techniques for quantification
      of Cl and Br concentrations that preclude extensive sample preparation.

PMID- 16906716
TI  - Structure elucidation of retinoids in biological samples using postsource decay
      laser desorption/ionization mass spectrometry after high-performance liquid
      chromatography separation.
AB  - Retinoids [retinol (vitamin A) and its metabolites] function in the visual cycle,
      embryonic development, cellular differentiation, and tissue homeostasis.
      Notwithstanding pivotal roles of retinoids in mammals, the limited number of
      commercially available retinoid standards is a major roadblock to identifying and
      studying retinoids in biological samples. Therefore, a need exists for improved
      methods to identify retinoid metabolites. We analyzed polar and nonpolar
      retinoids, including retinoic acid, retinol, retinyl acetate, and other retinyl
      esters, using postsource decay laser desorption/ionization mass spectrometry (PSD
      LDI MS). PSD analysis was employed to examine the PSD fragmentation patterns of
      retinoids, as these patterns can be used for the characterization of retinoids
      from biological samples without the need for matching retention time with a
      commercially available or synthetic retinoid. Mechanisms for the formation of
      these PSD fragment ions are proposed. The feasibility of employing PSD after HPLC
      separation was demonstrated by characterizing the endogenous retinoids in canine
      kidney epithelial cell extracts and in mouse lung. We show that the PSD-LDI MS
      approach described here can facilitate the identification and characterization of
      retinoids from mammalian cells and tissues.

PMID- 16906717
TI  - High-performance polymer-based monolithic capillary column.
AB  - In this report, we introduce a new entry of high-performance polymer-based
      monolithic capillary column for mainly small molecules. This capillary column was
      prepared using a newly introduced epoxy monomer with diamines. Simply heat
      induced polycondensation in an appropriate porogenic solvent afforded a really
      homogeneous co-continuous monolithic structure having submicrometer-size
      skeletons with micrometer-size through-pores. We were also able to prepare chiral
      monolithic columns using a chiral epoxy monomer as well as a chiral diamine. A
      21.5-cm-long, 100-mum-i.d. column afforded up to 40 000 theoretical plate numbers
      (N) for alkylbenzenes in 60% aqueous acetonitrile as a reversed-phase-mode
      stationary phase. Due to a quite low column pressure drop, a 150-cm-long column
      was prepared. This long column afforded up to 200 000 plates for alkylbenzenes
      with only a 4-MPa column pressure drop. In contrast, in 100% acetonitrile, this
      column has "HILIC" property to show up to 60 000 plates for methanol with a 17.5
      cm-long column. In this mode, we were able to separate nucleic acids. In
      addition, we have prepared a chiral column with both of the chiral epoxy monomers
      and an amine. This column was able to chirally discriminate a racemic alcohol in
      a reversed-phase mode.

PMID- 16906718
TI  - Structural characterization of neutral glycosphingolipids by thin-layer
      chromatography coupled to matrix-assisted laser desorption/ionization quadrupole
      ion trap time-of-flight MS/MS.
AB  - Rapid and convenient structural analysis of neutral glycosphingolipids (GSLs) was
      achieved by direct coupling of thin-layer chromatography (TLC) to matrix-assisted
      laser desorption/ionization quadrupole ion trap time-of-flight (MALDI-QIT-TOF)
      MS/MS. Positions of unstained GSL spots on developed TLC plates were determined
      by comparison to orcinol-stained references. A matrix solution of 2,5
      dihydroxybenzoic acid (DHB) in acetonitrile/water (1:1 v/v) was then added
      directly to the unstained GSL spots, and the GSLs were directly analyzed by MALDI
      QIT-TOF MS. The acetonitrile/water DHB solution proved to be suitable for MS/MS
      structural analysis with high sensitivity. MS/MS and MS/MS/MS of GSLs yielded
      simple and informative spectra that revealed the ceramide and long-chain base
      structures, as well as the sugar sequences. Hydroxy fatty acids in ceramide
      provided characteristic MS/MS fragment ions. GSLs were stained with primuline, a
      nondestructive dye, after TLC development, and successfully analyzed by MALDI-QIT
      TOF MS/MS with high sensitivity. Immunostaining of GSLs after TLC development is
      a powerful method for characterizing antibody-specific sugars, but not ceramides.
      By coupling TLC-immunostaining of GSLs to MALDI-QIT-TOF MS/MS, we were able to
      identify both the sugar and the ceramide structures. The detection limits of
      asialo GM1 (Galbeta1-3GalNAcbeta1-4Galbeta1-4Glcbeta1-1'Cer) were 25 and 50 pmol
      in primuline staining and immunostaining, respectively.

PMID- 16906719
TI  - Measurement of urinary monohydroxy polycyclic aromatic hydrocarbons using
      automated liquid-liquid extraction and gas chromatography/isotope dilution high
      resolution mass spectrometry.
AB  - A method for the measurement of 24 hydroxylated polycyclic aromatic hydrocarbon
      metabolites (OH-PAHs) in urine has been developed. The method is based on
      enzymatic deconjugation, automated liquid-liquid extraction, and gas
      chromatography/isotope dilution high-resolution mass spectrometry after
      derivatization of the OH-PAHs to the trimethylsilylated derivatives. The
      metabolites included in the current method are formed from eight different parent
      compounds. The limits of detection were below 7 pg/mL when using a sample size of
      2 mL of urine, except for 1- and 2-naphthols (18 and 12 pg/mL, respectively). The
      enzymatic deconjugation efficiency, verified by deconjugation of urine samples
      spiked with alpha-naphthyl beta-d-glucuronide sodium salt (1-NAP-GLU) and pyrene
      1-sulfate potassium salt (1-PYR-SULF), was determined to be 97% for 1-NAP-GLU
      conjugate and 84% for 1-PYR-SULF. The overall coefficients of variance for six
      batches of quality control samples (n = 42), was 2.9-11%. Mean method recoveries
      of the 13C-labeled internal standards were 66-72%, except for 13C6-1-naphthol
      (46%). The throughput of this method has been determined to be 40 samples per day
      per analyst. This method is currently applied to epidemiological studies, such as
      the National Exposure and Nutrition Examination Survey (NHANES), to measure human
      exposure to PAHs.

PMID- 16906720
TI  - Automated quantification tool for high-throughput proteomics using stable isotope
      labeling and LC-MSn.
AB  - LC-MSn has become a popular option for high-throughput quantitative proteomics,
      thanks to the availability of stable-isotope labeling reagents. However, the vast
      quantity of data generated from LC-MSn continues to make the postacquisition
      quantification analyses challenging, especially in experiments involving multiple
      samples per experimental condition. To facilitate data analysis, we developed a
      computer program, QUIL, for automated protein quantification. QUIL accounts for
      the dynamic nature of spectral background and subtracts this background
      accordingly during ion chromatogram reconstruction. For elution profile
      identification, QUIL minimizes the inclusion of coeluted neighbor peaks, yet
      tolerates imperfect peak shapes. Outlier-resistant methods have been implemented
      for better protein ratio estimation. The utility of QUIL was validated by
      quantitative analyses of a standard protein as well as complex protein mixtures,
      which were labeled with cICAT or 18O and analyzed using LCQ, LTQ, or FT-ICR
      instruments. For samples that no prior knowledge of relative protein quantities
      was available, Western blotting was performed for confirmation. For the standard
      protein, the coefficient of variation (CV) of peptide ratio estimation was 6%.
      For complex mixtures, the median CV for protein ratio calculations was less than
      10%. Computed protein abundance ratios exhibited a relatively high degree of
      correlation with those obtained from Western blot analyses. Compared with a
      widely used commercial software tool, QUIL showed improvement in ion chromatogram
      construction and peak integration and significantly reduced relative errors in
      abundance ratio assessment.

PMID- 16906721
TI  - Quantification of intermediate-abundance proteins in serum by multiple reaction
      monitoring mass spectrometry in a single-quadrupole ion trap.
AB  - A method is presented to quantify intermediate-abundance proteins in human serum
      using a single-quadrupole linear ion trap mass spectrometer-in contrast, for
      example, to a triple-quadrupole mass spectrometer. Stable-isotope-labeled
      (tryptic) peptides are spiked into digested protein samples as internal
      standards, aligned with the traditional isotope dilution approach. As a proof-of
      concept experiment, four proteins of intermediate abundance were selected,
      coagulation factor V, adiponectin, C-reactive protein (CRP), and thyroxine
      binding globulin. Stable-isotope-labeled peptides were synthesized with one
      tryptic sequence from each of these proteins. The normal human serum
      concentration ranges of these proteins are from 1 to 30 microg/mL (or 20 to 650
      pmol/mL). These labeled peptides and their endogenous counterparts were analyzed
      by LC-MS/MS using multiple reaction monitoring, a multiplexed form of the
      selected reaction monitoring technique. For these experiments, only one
      chromatographic dimension (on-line reversed-phase capillary column) was used.
      Improved limits of detection will result with multidimensional chromatographic
      methods utilizing more material per sample. Standard curves of the spiked
      calibrants were generated with concentrations ranging from 3 to 700 pmol/mL using
      both neat solutions and peptides spiked into the complex matrix of digested serum
      protein solution where ion suppression effects and interferences are common.
      Endogenous protein concentrations were determined by comparing MS/MS peak areas
      of the endogenous peptides to the isotopically labeled internal calibrants. The
      derived concentrations from a normal human serum pool (neglecting loss of
      material during sample processing) were 9.2, 110, 120, and 246 pmol/mL for
      coagulation factor V, adiponectin, CRP, and thyroxine binding globulin,
      respectively. These concentrations generally agree with the reported normal
      ranges for these proteins. As a measure of analytical reproducibility of this
      single-quadrupole assay, the coefficients of variance based on 12 repeated
      measurements for each of the endogenous tryptic peptides were 17.0, 25.4, 24.2,
      and 14.0% for coagulation factor V, adiponectin, CRP, and thyroxine binding
      globulin, respectively.

PMID- 16906722
TI  - Quantitative analysis of deuterium using laser-induced plasma at low pressure of
      helium.
AB  - It was proved that the analysis of deuterium can be conducted using laser-induced
      plasma spectroscopy. By selecting the appropriate surrounding gas, its pressure,
      and gating time of the detection system, it was shown that the emission lines of
      both hydrogen (H(alpha)) and deuterium (D(alpha)), separated by only 0.179 nm,
      can be fully resolved. A linear calibration curve was also obtained, indicating
      that this technique has the potential for quantitative analysis of deuterium. The
      minimum detection limit achieved in this stage of research was estimated to be 50
      ppm. We have also shown that this technique can be used as a simple and rapid
      method for D and H analysis in solid samples.

PMID- 16906723
TI  - Theory of stepwise gradient elution in reversed-phase liquid chromatography
      coupled with flow rate variations: application to retention prediction and
      separation optimization of a set of amino acids.
AB  - The coupling of stepwise mobile phase gradient elution and flow programming is
      proposed as an integrated approach to the general elution problem in reversed
      phase liquid chromatography. A model is developed to describe the above
      separation process performed under simultaneous programming of two separation
      parameters by extending our previous work on the rigorous derivation of the
      fundamental equation governing the concentration gradient of organic modifier in
      the mobile phase, that is, a single gradient elution mode (Anal. Chem. 2005, 77,
      5670-5677). The theory was tested in the retention prediction and separation
      optimization of 18 o-phthalaldehyde derivatives of amino acids in eluting systems
      modified by acetonitrile or methanol. The retention prediction obtained for all
      solutes under all dual-mode gradient conditions was excellent. In addition, it
      has been shown that the combination of mobile phase and flow rate programming
      modes is particularly favorable, whereas the separations among the analytes were
      considerably improved by using the acetonitrile eluting system, as compared to
      those obtained by the methanol system.

PMID- 16906724
TI  - Kinetic calibration for automated hollow fiber-protected liquid-phase
      microextraction.
AB  - Recently, a kinetic calibration method was developed for the quantification of
      microextraction. In this study, we proved that the sample volume and sampling
      time do not affect the feasibility of the calibration method, theoretically. The
      new theoretical considerations of the kinetic calibration method were validated
      through the investigation of the kinetics of the absorption and desorption
      processes of hollow fiber-protected liquid-phase microextractrion (HF-LPME). The
      kinetic calibration method for HF-LPME was successfully used to correct the
      matrix effects in the carbaryl analysis of a red wine sample. This research
      extends the kinetic calibration approach to fast sampling and some in-vial
      analyses, whereby the sample volume is not much larger than the product of the
      distribution coefficient and the volume of the extraction phase. HF-LPME
      technique was successfully automated with a CTC CombiPal autosampler, and a new
      device was designed for the automation of HF-LPME in this study. All steps of the
      HF-LPME technique, including the filling of the extraction solvent, sample
      transfer and agitation, withdrawing the solvent to a syringe, and introducing the
      extraction phase into the injector, were automated by a CTC autosampler. The
      fully automated HF-LPME technique is more convenient and more accurate. The good
      reproducibility of the fully automated HF-LPME technique eliminates the need for
      an internal standard to improve the analytical precision. The automated HF-LPME
      technique can be also used to obtain the distribution coefficient between the
      sample matrix and the extraction phase. The distribution coefficients of carbaryl
      and (13)C-carbaryl between 1-octanol and red wine, at 25 degrees C, were obtained
      with this technique.

PMID- 16906725
TI  - Development of non-gel-based two-dimensional separation of intact proteins by an
      on-line hyphenation of capillary isoelectric focusing and hollow fiber flow field
      flow fractionation.
AB  - A rapid, non-gel-based, on-line, two-dimensional separation method is introduced
      for proteome analysis. Protein fractionation was carried out by first exploiting
      the differences in their respective isoelectric points (pI) in a Teflon capillary
      using isoelectric focusing (IEF), followed by a molecular weight (MW)-based
      separation in a hollow fiber by flow field-flow fractionation (FlFFF). The method
      developed here (CIEF-HFFlFFF) may be a powerful alternative to two-dimensional
      polyacrylamide gel electrophoresis, which is currently used for the separation
      and purification of proteins. In CIEF-HFFlFFF, proteins can be collected as a
      fraction of a certain pI and MW interval without being denatured. Additionally,
      the ampholyte solution is simultaneously removed during separation in the hollow
      fiber, and the overall process time is significantly reduced. This method was
      applied to a human urinary proteome sample, leading to the identification of 114
      proteins with the subsequent off-line use of nanoflow liquid chromatography
      tandem mass spectrometry after the tryptic digestion of each collected protein
      fraction.

PMID- 16906726
TI  - Fluorescence-based zinc ion sensor for zinc ion release from pancreatic cells.
AB  - In this paper, we describe the synthesis and characterization of analytical
      properties of fluorescence-based zinc ion-sensing glass slides and their
      application in monitoring zinc ion release from beta pancreatic cells in cell
      cultures. To fabricate the sensors, the zinc ion indicator ZnAF-2 {6-[N-[N',N'
      bis(2-pyridinylmethyl)-2-aminoethyl]amino-3',6'-dihydroxyspiro[isobenzofuran
      1(3H),9'-[9H]xanthene]-3-one} was modified to include a sufficiently long linking
      aliphatic chain with a terminal carboxyl functional group. The recently
      synthesized ZnAF-2 zinc ion indicator provided high zinc ion selectivity in
      physiological solutions containing millimolar levels of calcium and other
      possible interfering cations. The carboxyl-modified ZnAF-2 was conjugated to the
      activated surface of glass slides, which then served as zinc ion sensors. It was
      possible to grow pancreatic cells directly on the zinc-sensing glass slide or on
      a membrane placed on these glass slides. The sensors were used to monitor zinc
      ion release events from glucose-stimulated pancreatic cells. The study showed
      that the zinc ion sensors responded effectively to the release of zinc ions from
      pancreatic cells at the nanomolar level with high selectivity and rapid subsecond
      response time.

PMID- 16906727
TI  - Facilitated transfer of alkali-metal cations by dibenzo-18-crown-6 across the
      electrochemically polarized interface between an aqueous solution and a
      hydrophobic room-temperature ionic liquid.
AB  - The facilitated transfer of alkali metal cations (Li+, Na+, K+, Rb+, Cs+) by
      dibenzo-18-crown-6 (DB18C6) across the electrochemically polarizable interface
      between an aqueous solution (W) and a hydrophobic ionic liquid, N
      octadecylisoquinolinium tetrakis[3,5-bis(trifluoromethyl)phenyl]borate
      ([C18Iq][TFPB]), has been studied using cyclic voltammetry at the interface
      formed at the tip of a micropipet. In cyclic voltammograms (CVs), the current due
      to the facilitated transfer of the cations by DB18C6 from W to [C18Iq][TFPB] can
      be measured within the polarized potential window of the [C(18)Iq][TFPB]|W
      interface. The stoichiometry of the complexes in [C18Iq][TFPB] for Li+, Na+, K+,
      and Rb+ are found to be 1:1 while for the Cs+ transfer both 1:1 and 1:2 complexes
      are likely to be formed. The formation constants of the 1:1 complexes for Li+,
      Na+, K+, and Rb+ in [C18Iq][TFPB], , evaluated from CVs are log = 5.0, 7.0, 8.2,
      and 7.3, respectively. The value for K+ is 1 order of magnitude greater than that
      for Na+. This higher selectivity of DB18C6 to K+ over Na+ in [C18Iq][TFPB]
      compared with that in molecular solvents suggests that the RTIL provides a unique
      solvation environment for the complexations of DB18C6 with the ions.

PMID- 16906728
TI  - Structure-function relationships in high-density docosylsilane bonded stationary
      phases by Raman spectroscopy and comparison to octadecylsilane bonded stationary
      phases.
AB  - Raman spectroscopy is used to investigate the effects of temperature, surface
      coverage, polymerization method (surface or solution polymerized), and nature of
      the alkylsilane precursor on alkyl chain conformational order in a series of high
      density docosylsilane (C22) stationary phases at surface coverages ranging from
      3.61 to 6.97 mumol/m(2). The results of this study contribute to an enhanced
      understanding of the shape-selective retention characteristics of these phases at
      a molecular level. Conformational order is evaluated using the intensity ratio of
      the antisymmetric and symmetric nu(CH2) modes as well as the frequency at which
      these modes are observed. Alkyl chain order is shown to be dependent on surface
      coverage, alkyl chain length, and polymerization method. In general, alkyl chain
      order increases with surface coverage. Temperature-induced changes are observed
      between 250 and 350 K for the three phases with surface coverages between 3.61
      and 4.89 mumol/m(2). These changes occur over a broad range of temperatures
      characteristic of two-dimensional systems, but in general adhere to the behavior
      predicted for a simple first-order transition. This change is not believed to be
      an abrupt cooperative disassociation characteristic of a phase transition in a
      bulk phase, but instead is thought to involve significant changes in
      conformational order in segments of the surface-tethered molecules, mostly those
      segments at the outer edge of the alkylsilane. In contrast to the changes
      observed in coverages below 5 mumol/m(2), a first-order change is not observed
      for the stationary phase with coverage of 6.97 mumol/m(2). A molecular picture of
      the temperature-induced disorder is proposed with disorder originating at the
      distal carbon and propagating only a short distance toward the proximal carbon. A
      comparison is made between these C22 stationary phases and similar high-density
      octadecylsilane (C18) bonded phases.

PMID- 16906729
TI  - Heterogeneity of the adsorption mechanism of low molecular weight compounds in
      reversed-phase liquid chromatography.
AB  - The retention mechanism in RPLC mode was investigated based on the acquisition of
      adsorption isotherm data by frontal analysis measurements and their modeling.
      This work is a review of the results of four years of adsorption data
      measurements. The data were acquired on a wide variety of brands of C18-silica
      columns (from Akzo Nobel, Bishoff, Hypersil, Merck, Phenomenex, Supelco, Vydac,
      and Waters) with several low molecular weight compounds such as phenol (94
      g/mol), caffeine (194 g/mol), tryptophan (204 g/mol), sodium 2
      naphthalenesulfonate (235 g/mol), and propranololium chloride (295 g/mol). The
      mobile phase was a mixture of methanol and water at variable composition. The
      adsorption isotherms were all convex upward (langmuirian), and the degree of
      heterogeneity of the adsorption system was determined from the calculation of the
      adsorption energy distribution using the expectation-maximization method. The
      adsorption isotherm parameters (number of types of adsorption sites, surface
      concentration of each type of site, and difference between the adsorption
      energies E(i) - E(j) on sites i and j), obtained from the mathematical fit of the
      adsorption data to the appropriate multi-Langmuir adsorption isotherm model, were
      analyzed and compared. The results allow the drawing of general conclusions
      regarding the relationships between the size of the analyte and the adsorption
      properties (saturation capacities, adsorption energies) characterizing the
      retention mechanism in RPLC mode for neutral, anionic, and cationic compounds.

PMID- 16906730
TI  - Adjustable fragmentation in laser desorption/ionization from laser-induced
      silicon microcolumn arrays.
AB  - Laser-induced silicon microcolumn arrays (LISMA) were developed as matrix-free
      substrates for soft laser desorption/ionization mass spectrometry (SLDI-MS). When
      low-resistivity silicon wafers were irradiated in air, sulfur hexafluoride, or
      water environment with multiple pulses from a 3 x omega mode-locked Nd:YAG laser,
      columnar structures were formed on the surface. The radii of curvature of the
      column tips varied with the processing environment, ranging from approximately
      120 nm in water, to <1 mum in SF6, and to approximately 2 mum in air. In turn,
      these microcolumn arrays were used as matrix-free soft laser desorption
      substrates. In SLDI-MS experiments with a nitrogen laser, the microcolumn arrays
      obtained in water environment readily produced molecular ions for peptides and
      synthetic polymers at low laser fluence. These surfaces demonstrated the best ion
      yield among the three arrays. The threshold laser fluence and ion yield were
      comparable to those observed in matrix-assisted laser desorption/ionization. Low
      femtomole sensitivity and approximately 6000 Da mass range were achieved. At
      elevated laser fluence, efficient in-source decay was observed and extensive
      peptide sequence information was extracted from the resulting mass spectra. The
      versatility of LISMA was attributed to confinement effects due to the
      submicrometer morphology and to the surface, thermal, and optical properties of
      processed silicon.

PMID- 16906731
TI  - High-speed, whole-column fluorescence imaging detection for isoelectric focusing
      on a microchip using an organic light emitting diode as light source.
AB  - An integrated and simplified microfluidic device using a 250 microm x 1-4 cm of
      organic light emitting diode (OLED) array as a two-dimensional light source for
      single-channel and multichannel whole-column imaging detection was developed.
      This fluorescence detection system was used for isoelectric focusing (IEF) of R
      phycoerythrin in a microchip. The IEF conditions were optimized, and the total
      analysis time was extremely reduced to 30 s for 2-cm-long microchannels at 700
      V/cm of electric field strength without the presence of electroosmotic flow. The
      compression of pH gradient caused by electrolytes drawing into the microchannels
      was efficiently restrained when 1% hydroxylpropylmethyl cellulose in 2% ampholyte
      was used as the carrier for IEF. Under optimized IEF conditions, the detection
      limit of this system was approximately 0.6 microg/mL or 45 pg at 75 nL/column
      injection of R-phycoerythrin. This OLED-induced fluorescence detection system for
      WCID provides a high-speed IEF technique with quantitative ability and the
      potential for high integration and throughput microchip systems.

PMID- 16906732
TI  - Electrostatic switching of biopolymer layers. Insights from combined
      electrokinetics and reflectometric interference.
AB  - Structural integrity and functional characteristics of biomacromolecules are
      largely defined by electrostatic forces between ionized moieties, which are often
      altered at interfaces. Unraveling these changes requires access to charge state
      and structure of surface-confined biopolymers in aqueous environments. We
      therefore combined electrokinetic measurements of interfacial electrical
      potentials with the simultaneous determination of the optical layer thickness by
      reflectometric interference spectroscopy. Two examples are summarized to
      demonstrate the resulting options: The pH-switching of grafted poly(l-glutamic
      acid) layers caused by dissociation-dependent helix-coil transitions was studied;
      potential distribution and ion mobility within the grafted polyelectrolyte were
      unraveled using an new theoretical model for the charging of polyelectrolyte
      layers. The charge-driven modulation of biopolymers at interfaces was furthermore
      analyzed in the adsorption of fibronectin onto polymer substrates with varied
      charge density; the results permit us to reach a conclusion about the relevance
      of electrostatic matching for orientation and anchorage of the protein.
      Altogether, the introduced methodology was found suitable to follow the
      electrosurface characteristics of biomacromolecules in situ.

PMID- 16906733
TI  - Modeling retention and selectivity as a function of pH and column temperature in
      liquid chromatography.
AB  - In reversed-phase liquid chromatography (RPLC), the retention of weak acids and
      bases is a sigmoidal function of the mobile-phase pH. Therefore, pH is a key
      chromatographic variable to optimize retention and selectivity. Furthermore, at
      an eluent pH close to the pKa of the solute, the dependence of ionization of the
      buffer and solute on temperature can be used to improve chromatographic
      separations involving ionizable solutes by an adequate handling of column
      temperature. In this paper, we derive a general equation for the prediction of
      the retentive behavior of ionizable compounds upon simultaneous changes in mobile
      phase pH and column temperature. Four experiments, two limiting pH values and two
      temperatures, provide the input data that allow predictions in the whole range of
      these two variables, based on the thermodynamic fundamentals of the involved
      equilibria. Also, the study demonstrates the significant role that the choice of
      the buffer compound would have on selectivity factors in RPLC at temperatures
      higher than 25 degrees C.

PMID- 16906734
TI  - Preparation of an ion-exchange chromatographic support by a "grafting from"
      strategy based on atom transfer radical polymerization.
AB  - A new "grafting from" strategy based on surface-initiated atom transfer radical
      polymerization (ATRP) was first used for the preparation of a polymer-based ion
      exchange support for HPLC. The most important property of the proposed method is
      to be applicable for the synthesis of any type of ion exchanger in both the
      strong and the weak forms. Monodisperse, porous poly(glycidyl methacrylate-co
      ethylene dimethacrylate), poly(GMA-co-EDM) particles 5.8 mum in size were
      synthesized by "modified seeded polymerization". Poly(dihydroxypropyl
      methacrylate-co-ethylene dimethacrylate), poly(DHPM-co-EDM) particles were then
      obtained by the acidic hydrolysis of poly(GMA-co-EDM) particles. The ATRP
      initiator, 3-(2-bromoisobutyramido)propyl(triethoxy)silane was covalently
      attached onto poly(DHPM-co-EDM) particles via the reaction between
      triethoxysilane and diol groups. In the next stage, the selected monomer carrying
      strong cation exchanger groups, 3-sulfopropyl methacrylate (SPM), was polymerized
      on the initiator-immobilized particles via surface-initiated ATRP. The degree of
      polymerization of SPM (i.e., length of polyionic ligand) on the particles was
      precisely controlled by adjusting ATRP conditions. Poly(SPM)-grafted poly(DHPM-co
      EDM) particles obtained with different ATRP formulations were tried as
      chromatographic packing in the separation of proteins by ion-exchange
      chromatography. The proteins were successfully separated with higher column
      yields with respect to the previously proposed materials. The plate heights
      between 100 and 150 mum were achieved with the column packed with the particles
      carrying the shortest poly(SPM) chains. The plate height showed no significant
      increase with increasing flow rate in the range of 0.5-16 cm/min.

PMID- 16906735
TI  - Vacuum ultraviolet postionization of aromatic groups covalently bound to
      peptides.
AB  - Experiments demonstrate that peptides with ionization potentials (IPs) above 7.87
      eV can be single-photon-ionized in the gas phase with a molecular fluorine laser
      following prior chemical derivatization with one of several aromatic tags acting
      as chromophores. 4-(Dimethylamino)benzoic acid, 1-naphthylacetic acid, and 9
      anthracenecarboxylic acid (denoted Benz, Naph and Anth, respectively) behave as
      chromophores, allowing single-photon ionization for vacuum ultraviolet (VUV)
      laser light by lowering the IP of the tagged peptide. Anth-tagged peptides that
      are laser-desorbed from a substrate and subsequently postionized produce mass
      spectra dominated by the intact radical cation, although protonated ions and
      fragmented species are also observed. Electronic structure calculations on Anth
      tagged peptides indicate that in addition to lowering the ionization potential,
      the presence of the aromatic tag increases charge localization on and
      delocalization across the ring structure, which presumably stabilizes the radical
      cation. Measurements on several tagged peptides confirm this calculation and show
      that the stabilizing effect of the tag increases with the size of the conjugated
      system in the order Benz < Naph < Anth. The tagged hexapeptide Anth-GAPKSC
      exhibits the parent ion, whereas the Benz- and Naph-tagged peptides do not. These
      results are supported by the experimental comparison of Anth-tagged vs untagged
      tryptophan, further suggesting that VUV postionization of tagged high-IP species
      is a promising method for expanding the capabilities of mass spectrometric
      analyses of molecular species.

PMID- 16906736
TI  - Validated method for the determination of the ethanol consumption markers ethyl
      glucuronide, ethyl phosphate, and ethyl sulfate in human urine by reversed
      phase/weak anion exchange liquid chromatography-tandem mass spectrometry.
AB  - A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the
      determination of the ethanol consumption markers ethyl glucuronide (EtG), ethyl
      phosphate (EtP), and ethyl sulfate (EtS) in human urine was developed. A reversed
      phase/weak anion exchange type stationary phase demonstrated particular
      suitability for the analysis of these highly polar acids. Sample preparation was
      minimized to centrifugation and dilution of urine prior to injection. The method
      was validated in the range of 5-750 microg.L(-1) with 1:20 and 1:1000 diluted
      urine, which corresponds to actual concentration ranges of 0.1-15 and 5-750 mg.L(
      1) in undiluted samples. Method validation was carried out using six different
      lots of human urine. Over the entire calibration range intraday and interday
      precision (each n = 5, three concentration levels per dilution factor) adopted
      values between 0.6 and 4.7% and 0.8 and 12.1%, relative standard deviation,
      respectively. Corresponding accuracy values ranged between 94.2 and 113.5% and
      86.6 and 110.9%, respectively. Matrix effects (absolute/relative) were found to
      be present in minor extent (approximately -30% to +15% MS/MS signal alterations)
      and were well corrected by the employed isotopically labeled internal standards.
      The validated assay was applied to urine samples of a drinking study as well as
      postmortem specimens. It was possible to assess the principal potential of EtP as
      ethanol consumption marker. Elevated concentration levels were found in real
      samples; however, EtP seems to be less sensitive compared to the previously known
      ethanol phase II conjugates EtG and EtS.

PMID- 16906737
TI  - Analog signal acquisition from computer optical disk drives for quantitative
      chemical sensing.
AB  - Optoelectronic consumer products that are widely employed in the office and home
      attract attention for optical sensor applications due to (1) their cost advantage
      over analytical instruments produced only in small quantities, (2) robustness in
      operation due to the detailed manufacturability improvements, and (3) ease of
      operation. We demonstrate here a new approach for quantitative
      chemical/biochemical sensing when analog signals are acquired from conventional
      optical disk drives, and these signals are used for quantitative detection of
      optical changes of sensor films deposited on conventional CD and DVD optical
      disks. Because we do not alter manufacturing process of optical disks, any disk
      can be employed for deposition and readout of sensor films. The optical disk
      drives also perform their original function of reading and writing digital
      content to optical media because no optical modifications are introduced to
      obtain the analog signal. Such a sensor platform is quite universal and can be
      applied for chemical and biological quantitative detection, as well as for
      monitoring of changes of physical properties of regions deposited onto a CD or
      DVD (e.g., during combinatorial screening of materials). As a model example, we
      demonstrate the concept using chemical detection of ionic species such as Ca2+ in
      liquids (e.g., blood, urine, or water). Colorimetric calcium-sensitive sensor
      films were deposited onto a DVD, exposed to water with different concentrations
      of Ca2+, and quantified in the optical disk drive. The developed lab-on-DVD
      system demonstrated a 5 ppm detection limit of Ca2+ determinations, similar or
      slightly better than that achieved using a conventional fiber-optic portable
      spectrometer. This detection limit corresponded to a 0.023 absorbance unit
      resolution, as determined by the measurement of the same colorimetric films with
      a portable spectrometer. Determinations of Ca2+ unknowns using the lab-on-DVD
      system demonstrated +/-5 ppm accuracy and 2-5% relative standard deviation
      precision in predicting 100 ppm Ca2+.

PMID- 16906738
TI  - Lab-on-valve system integrating a chemiluminescent entity and in situ generation
      of nascent bromine as oxidant for chemiluminescent determination of tetracycline.
AB  - A novel configuration of a lab-on-valve (LOV) system was fabricated and applied
      for chemiluminescence (CL) detection by integrating a demountable Z-type flow
      cell onto the LOV unit. A bismuthate immobilized microcolumn was incorporated in
      one port of the LOV for in situ oxidation of KBr and generation of bromine as
      oxidant for the bromine-hydrogen peroxide-tetracycline (TC) chemiluminescent
      reaction. The nascent bromine reacts with hydrogen peroxide and produces a weak
      CL signal, the intensity of which was significantly enhanced in the presence of
      TC following an energy-transfer mechanism. A novel procedure for tetracycline
      quantification was therefore developed based on the present system. When compared
      with the reported flow injection-CL methods for TC, this procedure not only
      provided an improved detection limit of 2.0 microg L(-)(1) but also minimized
      sample and reagent consumption. A linear range of 6.0-10 000 microg L(-)(1) was
      derived along with RSD values of 5.9 (at the concentration level of
      quantification limit) and 2.2% (at 50 microg L(-)(1)), and a sampling frequency
      of 120 h(-)(1) was achieved. The system was validated with a National Standard
      Procedure (GB/T 18932.4-2002, HPLC with UV detection) by measuring TC contents in
      commercial milk samples.

PMID- 16906739
TI  - Atmospheric pressure photoionization fourier transform ion cyclotron resonance
      mass spectrometry for complex mixture analysis.
AB  - We have coupled atmospheric pressure photoionization (APPI) to a home-built 9.4-T
      Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometer. Analysis of
      naphtho[2,3-a]pyrene and crude oil mass spectra reveals that protonated
      molecules, deprotonated molecules, and radical molecular ions are formed
      simultaneously in the ion source, thereby complicating the spectra (>12 000 peaks
      per mass spectrum and up to 63 peaks of the same nominal mass), and eliminating
      the "nitrogen rule" for nominal mass determination of number of nitrogens.
      Nevertheless, the ultrahigh mass resolving power and mass accuracy of FT-ICR MS
      enable definitive elemental composition assignments, even for doublets as closely
      spaced as 1.1 mDa (SH3(13)C vs (12)C4). APPI efficiently ionizes nonpolar
      compounds that are unobservable by electrospray and allows nonpolar sulfur
      speciation of petrochemical mixtures.

PMID- 16906740
TI  - Approaches to quantifying and visualizing polyelectrolyte multilayer film
      formation on particles.
AB  - Colloidal particles prepared by using the layer-by-layer technique are
      increasingly finding application in diagnostics, drug delivery, and sensing.
      Herein, we outline methods for applying three established techniques, confocal
      laser scanning microscopy (CLSM), flow cytometry, and differential interference
      contrast (DIC) microscopy, to characterize ultrathin films of
      poly(styrenesulfonate) (PSS) and poly(allylamine hydrochloride) (PAH) assembled
      on silica particles. Both CLSM and flow cytometry require the use of
      fluorescently labeled polyelectrolytes (PEs). The film homogeneity can be
      assessed using CLSM, while flow cytometry allows analysis at unparalleled speed
      (thousands of particles per second) with unprecedented sensitivity (<0.5 fg of
      adsorbed polymer) of polydispersed particles of different size ( approximately
      300 nm to tens of micrometers). Using CLSM and flow cytometry measurements, in
      conjunction with quartz crystal microgravimetry measurements on planar supports,
      allows quantification of PSS/PAH layer buildup on the particles. Furthermore,
      flow cytometry and DIC microscopy were used to unequivocally distinguish between
      silica-core PSS/PAH-shell particles and hollow PSS/PAH capsules obtained
      following core removal. The techniques outlined here are not limited to measuring
      PE deposition on solid particles but, in principle, are equally applicable to
      quantifying the adsorption of other materials (such as DNA, proteins, or
      nanoparticles) on a variety of particulate systems, including hollow capsules,
      emulsions, and cells.

PMID- 16906741
TI  - Sequential determination of two proteins by temperature-triggered homogeneous
      chemiluminescent immunoassay.
AB  - A novel protocol for performing a sequential dual-protein immunoassay, based on a
      temperature-triggered separation/mixing process and HRP-catalyzed
      chemiluminescence (CL) detection, is described. In contrast to current multilabel
      based detection techniques, a single HRP label is employed in this proposed
      method. Herein we introduce poly(N-isopropylacrylamide) (PNIP) and magnetic beads
      as bimolecular immobilizing carriers to separate different targets by taking
      advantage of thermal response, as demonstrated by sequential detection of human
      IgG and IgA. PNIP is known to aggregate and precipitate out of water when the
      temperature is raised above the lower critical solution temperature (LCST) of 31
      degrees C; thus, it can be separated from supernatant by centrifugation. Besides,
      magnetic beads can be separated from PNIP by magnetic force as the temperature is
      lower than LCST. A homogeneous noncompetitive ELISA was employed, formed by
      primary antibodies immobilized onto the surface of magnetic beads and PNIP,
      antigen as IgG and IgA in the sample, and HRP-labeled second antibodies.
      Moreover, highly sensitive CL detection of HRP was applied, and the detection
      limits of IgG and IgA were as low as 2.0 and 1.5 ng/mL, respectively. Within the
      calibrated amount, the protocol had excellent precision within 11% for each
      target and was comparable in performance to commercial single-analyte ELISAs.
      Furthermore, the proposed method has been successfully applied to the
      determination of dual analyte in real samples without cross-reaction, and a good
      correlation was achieved after comparison with the conventional assay for IgG and
      IgA in 40 human serum samples.

PMID- 16906742
TI  - Silica-shelled single quantum dot micelles as imaging probes with dual or
      multimodality.
AB  - The present study describes a stabilization of single quantum dot (QD) micelles
      by a "hydrophobic" silica precursor and an extension of a silica layer to form a
      silica shell around the micelle using "amphiphilic" and "hydrophilic" silica
      precursors. The obtained product consists of approximately 92% single
      nanocrystals (CdSe, CdSe/ZnS, or CdSe/ZnSe/ZnS QDs) into the silica micelles,
      coated with a silica shell. The thickness of the silica shell varies, starting
      from 3-4 nm. Increasing the shell thickness increases the photoluminescence
      characteristics of QDs in an aqueous solution. The silica-shelled single CdSe/ZnS
      QD micelles possess a comparatively high quantum yield in an aqueous solution, a
      controlled small size, sharp photoluminescence spectra (fwhm approximately 30
      nm), an absence of aggregation, and a high transparency. The surface of the
      nanoparticles is amino-functionalized and ready for conjugation. A comparatively
      good biocompatibility is demonstrated. The nanoparticles show ability for
      intracellular delivery and are noncytotoxic during long-term incubation with
      viable cells in the absence of light exposure, which makes them appropriate for
      cell tracing and drug delivery. The presence of the hydrophobic layer between the
      QD and silica-shell ensures an incorporation of other hydrophobic molecules with
      interesting properties (e.g., hydrophobic paramagnetic substances, hydrophobic
      photosensitizers, membrane stabilizers, lipid-soluble antioxidants or
      prooxidants, other hydrophobic organic dyes, etc.) in the close proximity of the
      nanocrystal. Thus, it is possible to combine the characteristics of hybrid
      materials with the priority of small size. The silica-shelled single QD micelles
      are considered as a basis for fabrication of novel hybrid nanomaterials for
      industrial and life science applications, for example, nanobioprobes with dual
      modality for simultaneous application in different imaging techniques (e.g.,
      fluorescent imaging and functional magnetic resonance imaging).

PMID- 16906743
TI  - Wetting micro- and nanofluidic devices using supercritical water.
AB  - We describe a method for wetting micro- and nanofluidic devices with water or any
      other pure liquid. The process is performed by enclosing the fluidic device in a
      liquid-filled cell, heating the cell to a temperature above the critical point of
      the liquid, and subsequent cooling of the cell to room temperature. Because the
      process liquid is essentially a gas during wetting, arbitrary shapes can be
      wetted. We demonstrate wetting of micro- and nanostructures in a fused-silica
      device with only a single inlet. The process is low-cost, fast, safe, and very
      reliable.

PMID- 16906745
TI  - Molecular organogels. Soft matter comprised of low-molecular-mass organic
      gelators and organic liquids.
AB  - This Account presents recent advances in understanding how and why dilute
      solutions/sols of low-molecular-mass organic gelators (LMOGs) undergo microscopic
      phase separation to form self-assembled fibrillar networks in molecular
      organogels. Concepts are illustrated structurally at the subnanometer (molecular)
      to several millimeter (bulk) length scales and dynamically over time scales that
      follow the assembly of supersaturated solutions/sols into gel phases. Examples
      include both structurally complicated (ALSmolecules with aromatic, linking, and
      steroidal groups) and simple (n-alkanes or n-alkanes along whose chains a hetero
      group has been inserted) LMOGs in a wide range of organic liquids.

PMID- 16906744
TI  - Traceless capping agent for peptide sequencing by partial edman degradation and
      mass spectrometry.
AB  - An improved method for the rapid sequence determination of biologically active
      peptides selected from one-bead-one-peptide combinatorial libraries has been
      developed. In this method, beads carrying unique peptide sequences were subjected
      to multiple cycles of partial Edman degradation (PED) by the treatment with a 15
      30:1 mixture of phenyl isothiocyanate and N-(9
      fluorenylmethoxycarbonyloxy)succinimide (Fmoc-OSU), to generate a series of
      sequence-specific truncation products (a peptide ladder) for each resin-bound
      peptide. Following PED, the Fmoc group was removed from the N-terminus and any
      reacted side chains by piperidine treatment. The sequence of the full-length
      peptide on each bead was then determined by matrix-assisted laser desorption
      ionization mass spectrometry. The use of Fmoc-OSU as a traceless capping agent
      resulted in cleaner MS spectra and improved reliability for sequence assignment.
      This rapid, sensitive, and inexpensive sequencing method should further expand
      the utility of combinatorial peptide libraries in biomedical research.

PMID- 16906746
TI  - Hydrophobic and hydrophilic yoctowells.
AB  - Rigid molecular monolayers made of alpha,omega-diamido lipids form yoctoliter
      sized gaps ("yoctowells", 1 yL = 10(-24) L or 1 nm3) around porphyrin islands on
      smooth surfaces. Their hydrophobic walls adsorb cyclic edge amphiphiles, e.g.,
      trans-1,2-cyclohexanediol, cellobiose, and tyrosine, which fill-up the wells
      slowly and irreversibly by a process called "kinetic trapping". Wells with
      oligoethylene or oligoamide walls are effective as 3D-crown ethers or oligoamide
      barrels for reversible "thermodynamic trapping" of amines or amides. Three
      porphyrins A, B, and C were sorted as stacks within the yoctowells, and a
      methylammonium ring was established at their rim to fixate a fourth molecule D at
      a longer distance. Yoctowells are easy to prepare, characterize, and modify and
      provide simple models of biological modules.

PMID- 16906747
TI  - Search for solutions to the reactivity and selectivity problems in enyne
      metathesis.
AB  - Enyne metathesis is a powerful carbon-carbon bond-forming reaction to generate
      1,3-dienes from an alkyne and an alkene. Different from the diene and diyne
      metathesis, the enyne metathesis suffers from both regio- and stereoselectivity
      problems, yet there is no general solution to these problems. This Account
      briefly describes the evolution of various new strategies and substrate platforms
      from these laboratories to address the reactivity and selectivity issues in the
      enyne metathesis processes.

PMID- 16906748
TI  - Engaging zwitterions in carbon-carbon and carbon-nitrogen bond-forming reactions:
      A promising synthetic strategy.
AB  - An Account of carbon-carbon and carbon-nitrogen bond-forming reactions mediated
      by zwitterions generated by the addition of organic nucleophiles to activated
      unsaturated systems highlighting their synthetic potential is presented.

PMID- 16906749
TI  - Probing the cybotactic region in gas-expanded liquids (GXLs).
AB  - Gas-expanded liquids (GXLs) are a new and benign class of liquid solvents, which
      may offer many advantages for separations, reactions, and advanced materials.
      GXLs are intermediate in properties between normal liquids and supercritical
      fluids, both in solvating power and in transport properties. Other advantages
      include benign nature, low operating pressures, and highly tunable properties by
      simple pressure variations. The chemical community has only just begun to exploit
      the advantages of these GXLs for industrial applications. This Account focuses on
      the synergism of experimental techniques with theoretical modeling resulting in a
      powerful combination for exploring chemical structure and transport in the
      cybotactic region of GXLs (at the nanometer lengthscale).

PMID- 16906750
TI  - Applications of total synthesis to problems in neurodegeneration: Fascinating
      chemistry along the way.
AB  - The possibility for the application of organic synthesis to the discovery of new
      agents in combating neurodegenerative disorders is described. Our focus has been
      on agents derived from natural-product leads and natural products themselves
      prepared through total synthesis. Herein, we describe some of the chemistry as
      well as interesting observations made along the way.

PMID- 16906751
TI  - Domain relationships in thiamine diphosphate-dependent enzymes.
AB  - Three-dimensional structures have been determined for 13 different enzymes that
      use thiamine diphosphate (ThDP) as a cofactor. These enzymes fall into five
      families, where members within a family have similar structures. In different
      families, there are similarities between some domains that clearly point to a
      common ancestor for all of these enzymes. Where the enzyme structures differ,
      evolutionary relationships between families can be discerned. Here, I present an
      analysis of these families and propose an evolutionary pathway to explain the
      diversity of structures that are now known.

PMID- 16906752
TI  - Correlating structure with function in bacterial multicomponent monooxygenases
      and related diiron proteins.
AB  - Bacterial multicomponent monooxygenases (BMMs) catalyze the O2-dependent
      hydroxylation of hydrocarbons at a carboxylate-bridged diiron center similar to
      those that occur in a variety of dimetallic oxygen-utilizing enzymes. BMMs have
      found numerous biodegradation and biocatalytic applications. Recent
      investigations have begun to reveal how BMMs perform their C-H bond activation
      chemistry and why these enzymes may be mechanistically different from other
      related diiron proteins. The structures of the BMM component proteins and of
      complexes between them provide insights into the tuning of the dinuclear iron
      center and the enzyme mechanism. Selected findings are compared and contrasted
      with the properties of other carboxylate-bridged diiron proteins, revealing
      common structural and functional themes.

PMID- 16906753
TI  - Structure of the actuator domain from the Archaeoglobus fulgidus Cu(+)-ATPase.
AB  - Copper homeostasis is maintained in part by membrane-bound P(1B)-type ATPases
      that are found in all organisms and drive the transport of this essential, yet
      toxic, metal ion across cellular membranes. CopA from Archaeoglobus fulgidus is a
      hyperthermophilic member of this ATPase subfamily and is homologous to the human
      Wilson and Menkes disease ATPases. To gain insight into Cu(+)-ATPase function,
      the structure of the CopA actuator domain (A-domain) was determined to 1.65 A
      resolution. The CopA A-domain functions to couple ATP hydrolysis in the ATP
      binding domain (ATPBD) with structural rearrangements of critical transmembrane
      segments. Its fold is quite similar to that of the sarcoplasmic reticulum Ca(2+)
      ATPase (SERCA1) A-domain, with the exception of an external loop region. On the
      basis of sequence and structural comparisons, specific residues that probably
      interact with the CopA ATPBD have been identified. Comparisons to the Wilson and
      Menkes disease A-domains reveal the presence of an additional loop that may be
      associated with regulatory functions in eukaryotic Cu(+)-ATPases. Finally,
      several mutations in the Wilson and Menkes disease ATPases occur in the A-domain,
      and their likely effects on function can be inferred from the CopA A-domain
      structure.

PMID- 16906754
TI  - Role of native-state structure in rubredoxin native-state hydrogen exchange.
AB  - Amide exchange rates were measured for Pyrococcus furiosus (Pf) rubredoxin
      substituted with either Zn(II), Ga(III), or Ge(IV). Base-catalyzed exchange rate
      constants increase up to 3000-fold per unit charge for the highly protected
      amides surrounding the active site metal, yielding apparent residue-specific
      conformational energy decreases of more than 8 kcal/mol in a comparison of the
      Zn(II)- and Ge(IV)-substituted proteins. However, the exchange kinetics for many
      of the other amides of the protein are insensitive to these metal substitutions.
      These differential rates are inversely correlated with the distance between the
      amide nitrogen and the metal in the X-ray structure, out to a distance of at
      least 12 A, consistent with an electrostatic potential-dependent shifting of the
      amide nitrogen pK. This strongly correlated distance dependence is consistent
      with a nativelike structure for the exchange-competent conformations. The
      electric field potential within the interior of the rubredoxin structure gives
      rise to a change of as much as a million-fold in the rate for the exchange
      competent state of the individual amide hydrogens. Nevertheless, the strength of
      these electrostatic interactions in Pf rubredoxin appears to be comparable to
      those previously reported within other proteins. As a result, contrary to the
      conventional analysis of hydrogen exchange data, for exchange processes that
      occur via nonglobal transitions, the residual conformational structure will often
      modulate the observed rates. Although this necessarily complicates the estimation
      of the conformational equilibria of these exchange-competent states, this
      dependence on residual structure can provide insight into the conformation of
      these transient states.

PMID- 16906755
TI  - Truncation of motifs III and IV in human lens betaA3-crystallin destabilizes the
      structure.
AB  - The purpose of our study was to determine the effects of specific truncations on
      the structural properties of human betaA3-crystallin. The following eight
      deletion mutants of betaA3-crystallin were generated: (i) N-terminal extension
      (NTE) 21 amino acids (betaA3[21] mutant), (ii) NTE 22 amino acids (betaA3[22]
      mutant), (iii) NTE (betaA3[N] mutant), (iv) NTE plus motif I (betaA3[N+I]
      mutant), (v) NTE plus motifs I and II (betaA3[N+I+II] mutant), (vi) NTE plus
      motifs I and II and connecting peptide (betaA3[N+I+II+CP] mutant), (vii) motifs
      III and IV (betaA3[III+IV] mutant), and (viii) motif IV (betaA3 [IV] mutant). The
      DNA sequencing and MALDI-TOF mass spectrometric methods confirmed desired
      specific deletions, and the purified mutant proteins exhibited a single band
      during SDS-PAGE analysis. When ANS bound, all the mutant proteins exhibited
      fluorescence quenching and a red shift, suggesting that the truncations caused
      changes in the exposed hydrophobic patches. The CD spectra showed that deletion
      of either NTE or the N-terminal domain (motifs I and II) had a relatively weaker
      effect on the structural stability than deletion of the C-terminal domain (motifs
      III and IV). Intrinsic Trp fluorescence spectral studies suggested changes in the
      microenvironment of the mutant proteins following truncations. HPLC multiangle
      light scattering analyses showed that truncation led to higher-order aggregation
      compared to that in the wild-type protein. Equilibrium unfolding and refolding of
      WT betaA3 with urea were best fit to a three-state model with transition
      midpoints at 2.2 and 3.1 M urea. However, the two transition midpoints of
      betaA3[21] and betaA3[22] and betaA3[N] mutants were similar to those of the wild
      type, suggesting that these truncations had a minimal effect on structural
      stabilization. Further, the mutant proteins containing the N-terminal domain
      (i.e., betaA3[III+IV] and betaA3[IV] mutants) exhibited higher transition
      midpoints compared to the transition midpoints of the mutant protein with the C
      terminal domain (i.e., betaA3[N+I+II+CP] mutant). The results suggested that the
      N-terminal domain is relatively more stable than the C-terminal domain in betaA3
      crystallin.

PMID- 16906756
TI  - Existence of different but overlapping IgG- and IgM-binding sites on the globular
      domain of human C1q.
AB  - C1q is the first subcomponent of the classical complement pathway that binds
      antigen-bound IgG or IgM and initiates complement activation via association of
      serine proteases C1r and C1s. The globular domain of C1q (gC1q), which is the
      ligand-recognition domain, is a heterotrimeric structure composed of the C
      terminal regions of A (ghA), B (ghB), and C (ghC) chains. The expression and
      functional characterization of ghA, ghB, and ghC modules have revealed that each
      chain has some structural and functional autonomy. Although a number of studies
      have tried to identify IgG-binding sites on the gC1q domain, no such attempt has
      been made to localize IgM-binding site. On the basis of the information available
      via the gC1q crystal structure, molecular modeling, mutational studies, and
      bioinformatics, we have generated a series of substitution mutants of ghA, ghB,
      and ghC and examined their interactions with IgM. The comparative analysis of IgM
      and IgG-binding abilities of the mutants suggests that the IgG- and IgM-binding
      sites within the gC1q domain are different but may overlap. Whereas Arg(B108),
      Arg (B109), and Tyr(B175) mainly constitute the IgM-binding site, the residues
      Arg(B114), Arg(B129), Arg(B163), and His(B117) that have been shown to be central
      to IgG binding are not important for the C1q-IgM interaction. Given the location
      of Arg(B108), Arg (B109), and Tyr(B175) in the gC1q crystal structure, it is
      likely that C1q interacts with IgM via the top of the gC1q domain.

PMID- 16906757
TI  - Tropoelastin massively associates during coacervation to form quantized protein
      spheres.
AB  - Tropoelastin, the precursor of elastin, undergoes a rapid monomer to multimer
      association in an inverse temperature transition. This association culminates in
      the rapid formation of stable, optically distinct droplets of tropoelastin. Light
      scattering and microscope measurements reveal that these droplets are 2-6 microm
      in diameter. Scanning electron microscopy confirms that the droplets are
      spherical. Three-dimensional confocal image stacks based on the autofluorescence
      of tropoelastin reveal that droplets are loaded with hydrated tropoelastin.
      Droplets are viable intermediates in synthetic elastin macroassembly. Dense
      clusters of aggregated droplets and partially formed fibers develop when droplets
      are incubated in the presence of a lysyl oxidase. Lysine-reacting chemical and
      enzyme-assisted cross-linking conditions generate cross-linked beads due to
      interactions between multiple, surface-exposed lysine epsilon-amino groups.
      Droplets represent an efficient mechanism for the bolus delivery during
      elastogenesis of quantized packages of preaccreted tropoelastin.

PMID- 16906758
TI  - Osmoprotection of bacterial cells from toxicity caused by antimicrobial hybrid
      peptide CM15.
AB  - Antimicrobial peptides exist ubiquitously as a host defense system in a broad
      range of species, including insects, amphibians, and mammals. The binding of
      these peptides is followed by the disruption of cytoplasmic membranes, leading to
      bacterial cell death; however, the precise mechanism of membrane destruction has
      remained controversial. In this study, we have examined the mechanism of action
      for the antimicrobial peptide, CM15 (KWKLFKKIGAVLKVL), a chimeric peptide of
      cecropin and mellitin. We find that the cytotoxicity of CM15 against either E.
      coli or Pseudomonas aeruginosa can be mitigated by the addition of sugar or
      poly(ethylene glycol) osmolytes to the extracellular media. The dependence of
      osmoprotection on solute size suggests the formation of pores with an effective
      diameter of 2.2-3.8 nm. In contrast, no osmoprotection was observed for cell
      killing by the cationic detergent dodecyltrimethylammonium bromide. Osmolytes
      also protected cells against the cytotoxicity of CM15 expressed intracellularly
      as a C-terminal extension of the carrier protein ketosteroid isomerase (KSI).
      Osmoprotection against the intracellularly produced peptide was also dependent on
      osmolyte size, in a manner that was in agreement with that observed for
      extracellularly added synthetic CM15. These data indicate that the formation of
      discrete pores in the cytoplasmic membrane is a key factor in the mechanism of
      bacterial killing by CM15.

PMID- 16906759
TI  - The soluble acyl-acyl carrier protein synthetase of Vibrio harveyi B392 is a
      member of the medium chain acyl-CoA synthetase family.
AB  - The gene encoding the unique soluble acyl-acyl carrier protein synthetase (AasS)
      of the bioluminescent Vibrio harveyi strain B392 has been isolated by expression
      cloning in Escherichia coli. This enzyme catalyzes the ATP-dependent acylation of
      the thiol of acyl carrier protein (ACP) with fatty acids with chain lengths from
      C4 to C18. The gene (called aasS) encodes a protein of 60 kDa, a hexahistidine
      tagged version of which was readily expressed in E. coli and purified in large
      quantities. Surprisingly, the sequence of the encoded protein was significantly
      more similar to that of an acyl-CoA synthetase of the distantly related
      bacterium, Thermus thermophilus, than to that of the membrane-bound acyl-acyl
      carrier protein synthetase of E. coli, an enzyme that catalyzes the same reaction
      from a more closely related organism. Indeed, the AasS sequence can readily be
      modeled on the known crystal structures of the T. thermophilus acyl-CoA
      synthetase with remarkably high levels of conservation of the catalytic site
      residues. To test the possible role of AasS in the fatty aldehyde-dependent
      bioluminescence pathway of V. harveyi, the chromosomal aasS gene of the organism
      was disrupted by insertion of a kanamycin cassette by homologous recombination.
      The resulting aasS::kan strains retained low levels of acyl-acyl carrier protein
      synthetase consistent with prior indications of a second such activity in this
      bacterium. The mutant strains grew normally and had normal levels of
      bioluminescence but were deficient in the incorporation of exogenous octanoic
      acid into the cellular phospholipids of V. harveyi, particularly at low octanoate
      concentrations. These data indicate that AasS is responsible for a high-affinity
      and high-capacity uptake system that efficiently converts exogenous fatty acids
      into acyl-ACP species competent to enter the fatty acid biosynthetic cycle.

PMID- 16906760
TI  - Inhibition of protein phosphatase 2A activity by selective electrophile
      alkylation damage.
AB  - Protein serine/threonine phosphatase 2A (PP2A) is a critical regulator of
      numerous cellular signaling processes and a potential target for reactive
      electrophiles that dysregulate phosphorylation-dependent signal transduction
      cascades. The predominant cellular form of PP2A is a heterotrimeric holoenzyme
      consisting of a structural A, a variable B, and a catalytic C subunit. We studied
      the modification of two purified PP2A holoenzyme complexes (ABalpha(FLAG)C and
      ABdelta(FLAG)C) with two different thiol-reactive electrophiles, biotinyl
      iodoacetamidyl-3,6-dioxaoctanediamine (PEO-IAB) and the biotinamido-4-[4'
      (maleimidomethyl)cyclohexanecarboxamido]butane (BMCC). In vivo treatment of HEK
      293 cells with these electrophiles resulted in alkylation of all three PP2A
      subunits. Electrophile treatment of the immunopurified FLAG-tagged holoenzymes
      produced a concentration-dependent adduction of PP2A subunits, as observed by
      Western blot analysis. Although both electrophiles labeled all three PP2A
      subunits, only BMCC inhibited the catalytic activity of both holoenzymes.
      Alkylation patterns in the A and B subunits were identical for the two
      electrophiles, but BMCC alkylated four Cys residues in the C subunit that were
      not labeled by PEO-IAB. Homology between the catalytic subunits of PP1 and PP2A
      enabled generation of a comparative model structure for the C subunit of PP2A.
      The model structure provided additional insight into contributions of specific
      BMCC-Cys adducts to PP2A enzyme inhibition. The results indicate that site
      selectivity of protein adduction should be a critical determinant of the ability
      of electrophiles to affect cellular signaling processes.

PMID- 16906761
TI  - Crystal structure of NADP(H)-dependent 1,5-anhydro-D-fructose reductase from
      Sinorhizobium morelense at 2.2 A resolution: construction of a NADH-accepting
      mutant and its application in rare sugar synthesis.
AB  - Recombinant 1,5-anhydro-d-fructose reductase (AFR) from Sinorhizobium morelense S
      30.7.5 was crystallized in complex with the cofactor NADP(H) and its structure
      determined to 2.2 A resolution using selenomethionine SAD (refined R(work) and
      R(free) factors of 18.9 and 25.0%, respectively). As predicted from the sequence
      and shown by the structure, AFR can be assigned to the GFO/IDH/MocA protein
      family. AFR consists of two domains. The N-terminal domain displays a Rossmann
      fold and contains the cofactor binding site. The intact crystals contain the
      oxidized cofactor NADP(+), whose attachment to the cofactor binding site is
      similar to that of NADP(+) in glucose-fructose oxidoreductase (GFOR) from
      Zymomonas mobilis. Due to variations in length and sequence within loop regions
      L3 and L5, respectively, the adenine moiety of NADP(+) adopts a different
      orientation in AFR caused by residue Arg38 forming hydrogen bonds with the 2'
      phosphate moiety of NADP(+) and cation-pi stacking interactions with the adenine
      ring. Amino acid replacements in AFR (S10G, A13G, and S33D) showed that Ala13 is
      crucial for the discrimination between NADPH and NADH and yielded the A13G
      variant with dual cosubstrate specificity. The C-terminal domain contains the
      putative substrate binding site that was occupied by an acetate ion. As
      determined by analogy to GFOR and by site-directed mutagenesis of K94G, D176A,
      and H180A, residues Lys94, Asp176, and His180 are most likely involved in
      substrate binding and catalysis, as substitution of any of these residues
      resulted in a significant decrease in k(cat) for 1,5-AF. In this context, His180
      might serve as a general acid-base catalyst by polarizing the carbonyl function
      of 1,5-AF to enable the transfer of the hydride from NADPH to the substrate. Here
      we present the first structure of an AFR enzyme catalyzing the stereoselective
      reduction of 1,5-AF to 1,5-anhydro-d-mannitol, the final step of a modified
      anhydrofructose pathway in S. morelense S-30.7.5. We also emphasize the
      importance of the A13G variant in biocatalysis for the synthesis of 1,5-AM and
      related derivatives.

PMID- 16906762
TI  - Transesterification thio effects of phosphate diesters: free energy barriers and
      kinetic and equilibrium isotope effects from density-functional theory.
AB  - Primary and secondary kinetic and equilibrium isotope effects are calculated with
      density-functional methods for the in-line dianionic methanolysis of the native
      (unsubstituted) and thio-substituted cyclic phosphates. These reactions represent
      reverse reaction models for RNA transesterification under alkaline conditions.
      The effect of solvent is treated with explicit (single and double) water
      molecules and self-consistently with an implicit (continuum) solvation model.
      Singly substituted reactions at the nonbridging O(P1) position and bridging
      O(2)('), O(3)('), and O(5)(') positions and a doubly substituted reaction at the
      O(P1) and O(P2) positions were considered. Aqueous free energy barriers are
      calculated, and the structures and bond orders of the rate-controlling transition
      states are characterized. The results are consistent with available experimental
      data and provide useful information for the interpretation of measured isotope
      and thio effects used to probe mechanism in phosphoryl transfer reactions
      catalyzed by enzymes and ribozymes.

PMID- 16906763
TI  - Cyanide binding and heme cavity conformational transitions in Drosophila
      melanogaster hexacoordinate hemoglobin.
AB  - The reason for the presence of hemoglobin-like molecules in insects, such as
      Drosophila melanogaster, that live in fully aerobic environments has yet to be
      determined. Heme endogenous hexacoordination (where HisE7 and HisF8 axial ligands
      to the heme Fe atom are both provided by the protein) is a recently discovered
      mechanism proposed to modulate O(2) affinity in hemoglobins from different
      species. Previous results have shown that D. melanogaster hemoglobin 1 (product
      of the glob1 gene) displays heme endogenous hexacoordination in both the ferrous
      and ferric states. Here we present kinetic data characterizing the exogenous
      cyanide ligand binding process, and the three-dimensional structure (at 1.4 A
      resolution) of the ensuing cyano-met D. melanogaster hemoglobin. Comparison with
      the crystal structure of the endogenously hexacoordinated D. melanogaster
      hemoglobin shows that the transition to the cyano-met form is supported by
      conformational readjustment in the CD-D-E region of the protein, which removes
      HisE7 from the heme. The structural and functional features of D. melanogaster
      hemoglobin are examined in light of previous results achieved for human and mouse
      neuroglobins and for human cytoglobin, which display heme endogenous
      hexacoordination. The study shows that, despite the rather constant value for
      cyanide association rate constants for the ferric hemoproteins, different distal
      site conformational readjustments and/or heme sliding mechanisms are displayed by
      the known hexacoordinate hemoglobins as a result of exogenous ligand binding.

PMID- 16906764
TI  - T-state inhibitors of E. coli aspartate transcarbamoylase that prevent the
      allosteric transition.
AB  - Escherichia coli aspartate transcarbamoylase (ATCase) catalyzes the committed
      step in pyrimidine nucleotide biosynthesis, the reaction between carbamoyl
      phosphate (CP) and l-aspartate to form N-carbamoyl-l-aspartate and inorganic
      phosphate. The enzyme exhibits homotropic cooperativity and is allosterically
      regulated. Upon binding l-aspartate in the presence of a saturating concentration
      of CP, the enzyme is converted from the low-activity low-affinity T state to the
      high-activity high-affinity R state. The potent inhibitor N-phosphonacetyl-l
      aspartate (PALA), which combines the binding features of Asp and CP into one
      molecule, has been shown to induce the allosteric transition to the R state. In
      the presence of only CP, the enzyme is the T structure with the active site
      primed for the binding of aspartate. In a structure of the enzyme-CP complex
      (T(CP)), two CP molecules were observed in the active site approximately 7A
      apart, one with high occupancy and one with low occupancy. The high occupancy
      site corresponds to the position for CP observed in the structure of the enzyme
      with CP and the aspartate analogue succinate bound. The position of the second CP
      is in a unique site and does not overlap with the aspartate binding site. As a
      means to generate a new class of inhibitors for ATCase, the domain-open T state
      of the enzyme was targeted. We designed, synthesized, and characterized three
      inhibitors that were composed of two phosphonacetamide groups linked together.
      These two phosphonacetamide groups mimic the positions of the two CP molecules in
      the T(CP) structure. X-ray crystal structures of ATCase-inhibitor complexes
      revealed that each of these inhibitors bind to the T state of the enzyme and
      occupy the active site area. As opposed to the binding of Asp in the presence of
      CP or PALA, these inhibitors are unable to initiate the global T to R
      conformational change. Although the best of these T-state inhibitors only has a
      K(i) value in the micromolar range, the structural information with respect to
      their mode of binding provides important information for the design of second
      generation inhibitors that will have even higher affinity for the active site of
      the T state of the enzyme.

PMID- 16906765
TI  - Irreversible misfolding of diacylglycerol kinase is independent of aggregation
      and occurs prior to trimerization and membrane association.
AB  - Escherichia coli diacylglycerol kinase (DAGK) is a homotrimeric helical integral
      membrane protein in which a number of single-site mutations to cysteine are known
      to promote misfolding. Here, effects of other amino acid replacements have been
      explored using a folding assay based on the dilution of acidic urea/DAGK stock
      solutions into detergent/lipid mixed micelles. DAGK with an I110P or I110R
      mutation in the third transmembrane helix could not be purified because its
      expression was toxic to the E. coli host, most likely because of severe folding
      defects. Other mutations at Ile110 enhanced irreversible misfolding to varying
      degrees that generally correlated both with the polarity of the inserted amino
      acid and with the degree of protein destabilization. However, the I110W mutant
      was an exception in that it was highly misfolding prone while at the same time
      being more stable than the wild-type protein. This contrasts with I110Y, which
      also exhibited enhanced stability but folded with an efficiency similar to that
      of the wild type. For most mutants, the critical step leading to irreversible
      misfolding occurred for monomeric DAGK prior to trimerization and independent of
      association with mixed micelles. Misfolding of DAGK evidently involves the
      formation of incorrect monomer tertiary structure. Mutations appear to enhance
      misfolding by disfavoring the formation of correct structure rather than by
      directly stabilizing the misfolded state. Finally, when urea-solubilized DAGK was
      diluted into detergent/lipid-free buffer, it retained a significant degree of
      folding competency over a period of minutes. This property may be relevant to
      membrane protein folding in cells under conditions where the usual machinery
      associated with membrane integration is saturated, dysregulated, or
      dysfunctional.

PMID- 16906766
TI  - Cytosol has a small effect on protein backbone dynamics.
AB  - Cells are crowded with macromolecules, yet most biophysical information about
      proteins is obtained in dilute solution. To determine the impact of this
      dichotomy, we used nuclear magnetic resonance spectroscopy to measure the
      backbone (15)N T(1) and T(2) relaxation times and the {(1)H}-(15)N nuclear
      Overhauser enhancement (nOe) of uniformly (15)N-enriched apocytochrome b(5) in
      living Escherichia coli and in dilute solution. These data allowed us to assess
      the backbone dynamics of this partially folded protein in cells and in dilute
      solution. The two data sets were analyzed by using the model-free approach.
      Transfer from dilute solution to the cytosol has a quantitative effect on T(1),
      T(2), and nOe values. Most of the effects are attributed to an increase in the
      overall correlation time, caused by the increased viscosity of the cytosol
      compared to that of the dilute solution. Our main conclusion is that the cytosol
      does not alter the pattern of backbone dynamics of apocytochrome b(5). Increases
      in the time scale of both the picosecond and millisecond motions are observed,
      but the increases are less than approximately 30%.

PMID- 16906767
TI  - The SF3b155 N-terminal domain is a scaffold important for splicing.
AB  - Recruitment of U2 snRNP to the branch point sequence of introns is a necessary
      step in pre-mRNA splicing. In the current model, U2AF65, bound at the
      polypyrimidine tract of the intron, recruits U2 snRNP to the branch point
      sequence by interacting with the U2 snRNP protein SF3b155. We demonstrate that
      the N-terminal domain of SF3b155 contains multiple U2AF65 binding sites that are
      distinct from the binding site for the U2 snRNP protein p14, mapped to amino
      acids 396-424 of SF3b155. The N-terminal domain of SF3b155 appears to adopt a
      primarily unfolded structure but is functional to inhibit splicing in vitro. RNA
      binding studies show that the N-terminal domain of SF3b155 binds RNA
      nonspecifically and that the sites for U2AF65 binding and RNA binding are
      overlapping (or the same) within SF3b155. We propose that the N-terminal domain
      of SF3b155 adopts a primarily unfolded structure that functions as a scaffold to
      facilitate SF3b155's multiple protein-protein and protein-RNA interactions. The
      multiple U2AF65 binding sites on SF3b155 suggest a model in which multiple U2AF65
      molecules bound to the intron could enhance U2 snRNP recruitment to the branch
      point sequence.

PMID- 16906768
TI  - Structure, dynamics, and stability variation in bacterial albumin binding
      modules: implications for species specificity.
AB  - Protein G-related albumin-binding (GA) modules are frequently expressed on the
      surfaces of bacterial cells. The limited amino acid sequence variation among GA
      modules results in structural and functional differences with possible
      implications for bacterial pathogenesis and host specificity. In particular, the
      streptococcal G148-GA3 and F. magna ALB8-GA albumin-binding domains exhibit a
      degree of structural and dynamic diversity that may account for their varied
      affinities for different species of albumin. To explore the impact of GA module
      polymorphisms on albumin binding and specificity, we recently used offset
      recombinant PCR to shuffle seven artificially constructed representatives of the
      GA sequence space and scan the phage-displayed recombinant domains for mutations
      that supported binding to the phylogenetically distinct human and guinea pig
      serum albumins (HSA and GPSA) (Rozak et al. (2006) Biochemistry 45, 3263-3271).
      Surprisingly, phage selection revealed an overwhelming preference for a single
      recombinant domain (PSD-1, phage-selected domain-1) regardless of whether the
      phages were enriched for their abilities to bind one or both of these albumins.
      We describe here the NMR-derived structure, dynamics, and stability of unbound
      PSD-1. Our results demonstrate that increased flexibility is not a requirement
      for broadened specificity, as had been suggested earlier (Johansson et al. (2002)
      J. Mol. Biol. 316, 1083-1099), because PSD-1 binds the phylogenetically diverse
      HSA and GPSA even more tightly than G148-GA3 but is less flexible. The structural
      basis for albumin-binding specificity is analyzed in light of these new results.

PMID- 16906769
TI  - The unfolded state of NTL9 is compact in the absence of denaturant.
AB  - Interest in the unfolded state of proteins has grown with the realization that
      this state can have considerable structure in the absence of denaturants.
      Natively unfolded proteins, mutations that unfold proteins under native
      conditions, and changes in pH that induce unfolding are attractive models for the
      unfolded state in the absence of denaturant. The unfolded state of the N-terminal
      domain of ribosomal protein L9 (NTL9) was previously shown to contain significant
      non-native electrostatic interactions [Cho, J. H., Sato, S., and Raleigh, D. P.
      (2004) J. Mol. Biol. 338, 827-837]. NTL9 has a mixed alpha-beta structure and
      folds via a two-state mechanism. We have generated a model of the unfolded state
      of NTL9 in the absence of denaturant by substitution of an alanine for
      phenylalanine 5 located in the core of this protein. The CD spectrum of the
      variant, denoted as F5A, exhibits significantly less structure than the wild
      type; however, the mean residue ellipticity of F5A at 222 nm (-8200 deg cm(2)
      dmol(-)(1)) is considerably larger than expected for a fully unfolded protein,
      indicating that residual secondary structure is populated. F5A also has more
      residual structure than the urea-unfolded wild type. The stability of F5A is
      estimated to be at least 1 kcal/mol unfavorable, showing that the unfolded state
      is populated to 84% or more. NMR pulsed-field gradient measurements yield a
      hydrodynamic radius of 16.1 A for wild-type NTL9 and 20.8 A for the F5A variant
      in native buffer. The physiologically relevant unfolded state of wild-type NTL9
      is likely to be even more compact than F5A since the mutation should reduce the
      level of hydrophobic clustering in the unfolded state in the absence of
      denaturant. The hydrodynamic radius of F5A increases to 25.9 A in 8 M urea, and a
      value of 23.5 A is obtained for the wild type under similar conditions. The
      results show that the unfolded state of F5A in the absence of denaturant is more
      compact and contains more structure than the urea-unfolded form.

PMID- 16906770
TI  - Stoichiometry of LTbetaR binding to LIGHT.
AB  - LTbetaR is a member of the TNF receptor family of proteins. It binds to two
      different cell surface ligands, LIGHT, a homotypic trimer, and LTalpha1beta2, a
      heterotypic trimer. We have measured the affinities of the dimeric IgG fusion
      protein, LTbetaRIgG, and monomeric LTbetaR protein binding to both LIGHT and
      LTalpha1beta2 using surface plasmon resonance and found values of <0.1 and 38 nM
      for LIGHT and <0.1 and 48 nM for LTalpha1beta2, respectively. We also determined
      the stoichiometries of binding for both forms of the receptor LTbetaRIgG and
      LTbetaR binding to LIGHT. The data obtained from several biophysical methods are
      consistent with receptor polypeptide to trimeric ligand ratios of 2:1. The
      determined masses of the complexes using SEC-LS corresponded to a single
      LTbetaRIgG bound to a LIGHT trimer, or two LTbetaR bound per LIGHT. Sedimentation
      velocity of varied ratios of LTbetaR to a fixed concentration of LIGHT were
      analyzed by SEDANAL and were successfully fit with a model with two tight binding
      sites on LIGHT and one poor affinity site. Isothermal calorimetric titration of
      LIGHT with either LTbetaR or LTbetaRIgG also demonstrated stoichiometries of 1:2
      and 1:1, respectively. The binding of LTbetaR to LIGHT was endothermic and,
      hence, entropy-driven. TNFR p55 (extracellular domain) complexed with the
      trimeric ligand, TNFbeta, exhibits a 3:1 receptor/ligand stoichiometry. This
      complex has been used as the prototypical model setting the receptor-ligand
      complexation paradigm for the entire TNF family. The LTbetaR/LIGHT binding
      stoichiometry of 2:1 demonstrated here does not fit the paradigm. This has
      numerous implications for cell biology including signaling requiring only
      dimerization of LTbetaR rather than trimerization as expected from the structural
      paradigm.

PMID- 16906771
TI  - Characterization of Kir1.1 channels with the use of a radiolabeled derivative of
      tertiapin.
AB  - Inward rectifier potassium channels (Kir) play critical roles in cell physiology.
      Despite representing the simplest tetrameric potassium channel structures, the
      pharmacology of this channel family remains largely undeveloped. In this respect,
      tertiapin (TPN), a 21 amino acid peptide isolated from bee venom, has been
      reported to inhibit Kir1.1 and Kir3.1/3.4 channels with high affinity by binding
      to the M1-M2 linker region of these channels. The features of the peptide-channel
      interaction have been explored electrophysiologically, and these studies have
      identified ways by which to alter the composition of the peptide without
      affecting its biological activity. In the present study, the TPN derivative, TPN
      Y1/K12/Q13, has been synthesized and radiolabeled to high specific activity with
      (125)I. TPN-Y1/K12/Q13 and mono-iodo-TPN-Y1/K12/Q13 ([(127)I]TPN-Y1/K12/Q13)
      inhibit with high affinity rat but not human Kir1.1 channels stably expressed in
      HEK293 cells. [(125)I]TPN-Y1/K12/Q13 binds in a saturable, time-dependent, and
      reversible manner to HEK293 cells expressing rat Kir1.1, as well as to membranes
      derived from these cells, and the pharmacology of the binding reaction is
      consistent with peptide binding to Kir1.1 channels. Studies using chimeric
      channels indicate that the differences in TPN sensitivity between rat and human
      Kir1.1 channels are due to the presence of two nonconserved residues within the
      M1-M2 linker region. When these results are taken together, they demonstrate that
      [(125)I]TPN-Y1/K12/Q13 represents the first high specific activity radioligand
      for studying rat Kir1.1 channels and suggest its utility for identifying other
      Kir channel modulators.

PMID- 16906772
TI  - Polychlorinated biphenyl quinone metabolites poison human topoisomerase IIalpha:
      altering enzyme function by blocking the N-terminal protein gate.
AB  - Polychlorinated biphenyls (PCBs) are associated with a broad spectrum of human
      health problems and cause cancer in rodents. In addition, these compounds cause
      chromosomal aberrations in humans and treated human cells. Although the
      underlying basis for the chromosomal damage induced by PCBs is not understood, it
      is believed that these compounds act through a series of phenolic and quinone
      based metabolites. Recent studies indicate that several quinones that promote
      chromosomal damage also act as topoisomerase II poisons. Therefore, the effects
      of PCB quinone metabolites (including mono and dichlorinated compounds and p- and
      o-quinones) on the activity of human topoisomerase IIalpha were examined. Results
      indicate that these compounds are potent topoisomerase IIalpha poisons in vitro
      and act by adducting the enzyme. They also increase DNA cleavage by topoisomerase
      IIalpha in cultured human cells. In contrast, incubation of topoisomerase IIalpha
      with PCB metabolites in the absence of DNA leads to a rapid loss of enzyme
      activity. On the basis of (1) the differential ability of quinone-treated enzyme
      to bind circular and linear DNA molecules and (2) the generation of salt-stable
      noncovalent complexes between topoisomerase IIalpha and circular plasmids in the
      presence of PCB quinones, it appears that these compounds alter enzyme function
      (at least in part) by blocking the N-terminal gate of the protein. Finally,
      exposure to quinones generates a protein species with a molecular mass
      approximately twice that of a monomeric topoisomerase IIalpha protomer. This
      finding suggests that PCB quinones block the N-terminal gate by cross-linking the
      protomer subunits of topoisomerase IIalpha.

PMID- 16906773
TI  - Identity elements for specific aminoacylation of a tRNA by mammalian lysyl-tRNA
      synthetase bearing a nonspecific tRNA-interacting factor.
AB  - Mammalian lysyl-tRNA synthetase (LysRS) has an N-terminal polypeptide chain
      extension appended to a prokaryotic-like synthetase domain. This extension,
      termed a tRNA-interacting factor (tIF), possesses a RNA-binding motif
      [KxxxK(K/R)xxK] that binds nonspecifically the acceptor TPsiC stem-loop domain of
      tRNA and provides a potent tRNA binding capacity to this enzyme. Consequently,
      native LysRS aminoacylates a RNA minihelix mimicking the amino acid acceptor stem
      loop domain of tRNA(3)(Lys). Here, examination of minihelix recognition showed
      that mammalian LysRS aminoacylates RNA minihelices without specificity of
      sequence, revealing that none of the nucleotides from the acceptor TPsiC stem
      loop domain are essential determinants of tRNA(Lys) acceptor identity. To test
      whether the tIF domain reduces the specificity of the synthetase with regard to
      complete tRNA molecules, aminoacylation of wild-type and mutant noncognate tRNAs
      by wild-type or N-terminally truncated LysRS was examined. The presence of the
      UUU anticodon of tRNA(Lys) appeared to be necessary and sufficient to transform
      yeast tRNA(Asp) or tRNA(i)(Met) into potent lysine acceptor tRNAs. Thus,
      nonspecific RNA-protein interactions between the acceptor stem of tRNA and the
      tIF domain do not relax the tRNA specificity of mammalian LysRS. The possibility
      that interaction of the full-length cognate tRNA with the synthetase is required
      to induce the catalytic center of the enzyme into a productive conformation is
      discussed.

PMID- 16906775
TI  - Oral anticoagulants in development: focus on thromboprophylaxis in patients
      undergoing orthopaedic surgery.
AB  - Current anticoagulant provision is dominated by parenteral heparin and oral
      warfarin, which act by inhibiting several steps of the coagulation pathway
      indirectly. Recent research efforts have focused on the identification of small
      molecule inhibitors of the coagulation enzymes as novel therapies for thrombotic
      disorders. There has been particular success in developing nonpeptidic, orally
      available, small molecules to directly inhibit the key proteases, factor IIa and
      factor Xa. Of the new oral anticoagulants in development, the two agents in the
      most advanced stage are dabigatran etexilate (BIBR 1048) and rivaroxaban (BAY 59
      7939), which inhibit factor IIa and factor Xa, respectively. Other agents in the
      early stages of development include several Xa inhibitors (LY-517717, YM150, DU
      176b and apixaban [BMS-562247]), a factor IXa inhibitor (TTP889), and an orally
      active glycosaminoglycan enhancer (odiparcil [SB-424323]), which indirectly
      enhances thrombin inhibition via heparin cofactor II. Results have been reported
      from important, phase II dose-finding studies, and a number of registration-track
      phase III studies have been initiated, reflecting the drive towards potentially
      more effective, but primarily safer and more convenient therapies for the
      prevention and treatment of venous and arterial thrombosis. Indeed, two unmet
      needs for anticoagulation that can be easily identified are safety and ease of
      use. Safety relates primarily to the incidence of major bleeding and this remains
      the key concern of orthopaedic surgeons, over and above any efficacy advantage,
      and convenience of use, which centres on oral administration replacing the need
      for injections. The clinical development of these new anticoagulants is following
      the well tested strategy of dose-ranging and registration studies in major
      orthopaedic surgery, prior to development in arterial indications. There are a
      number of subtle issues, including the timing of the first perioperative dose,
      duration of prophylactic treatment and definition/assessment of study endpoints
      that can influence study outcome and require careful consideration when
      evaluating study results with new agents and in the comparison with established
      agents, and which are considered in this review. It is anticipated that over the
      next 3 years, at least one of these agents will be successfully licensed for the
      prevention of venous thromboembolism after major orthopaedic surgery, which will
      act as a springboard for the gradual replacement of current anticoagulants.

PMID- 16906776
TI  - Biological therapy in the management of recent-onset Crohn's disease: why, when
      and how?
AB  - Crohn's disease is a chronic inflammatory bowel disease that may involve any part
      of the gastrointestinal tract. Conventional therapy consists of corticosteroids,
      azathioprine or methotrexate, but the clinical management of Crohn's disease is
      significantly hampered by adverse effects. With the introduction of biological
      agents (such as infliximab), the goals of therapy have advanced, including
      induction of remission with bowel healing as well as reduction in the rate of
      complications, surgeries and mortality. Current therapy for moderate to severe
      Crohn's disease is based on 'step-up' algorithms, which initiate treatment with
      corticosteroids followed by immunomodulatory agents, and defer therapy with
      biological agents until patients become refractory to conventional therapeutics.
      Recently, it has been shown that induction therapy with infliximab and
      azathioprine in recent-onset Crohn's disease (i.e. 'top-down' approach) is
      superior to current step-up algorithms to induce clinical remission. The
      underlying molecular mechanisms responsible for these differences in clinical
      outcome remain to be defined. Experimental studies have demonstrated that
      corticosteroids are able to induce impaired apoptosis of immune cells, including
      T cells and dendritic cells, resulting in loss of tolerance and subsequent
      autoimmunity. Further research will have to determine whether corticosteroid
      therapy augments the mechanism of loss of tolerance in Crohn's disease, which
      could complicate future clinical management.

PMID- 16906779
TI  - Beclometasone dipropionate/formoterol: in an HFA-propelled pressurised metered
      dose inhaler.
AB  - A hydrofluoroalkane (HFA)-propelled pressurised metered-dose inhaler (pMDI) has
      been developed (using Modulite technology) for a new fixed combination of
      beclometasone dipropionate/formoterol fumarate (BDP/formoterol) 100 microg/6
      microg. Each actuation of the BDP/formoterol HFA pMDI 100 microg/6 microg
      delivers 86.4 microg of BDP and 5 microg of formoterol. BDP/formoterol HFA pMDI
      was associated with significantly higher morning peak expiratory flow (PEF)
      values than BDP administered alone via a chlorofluorocarbon (CFC) pMDI (including
      when BDP was administered at a higher dosage) in well designed trials in adults
      with mild to moderate or moderate to severe asthma. In terms of morning PEF
      values, BDP/formoterol HFA pMDI was noninferior to BDP plus formoterol
      administered via separate inhalers in well designed trials in adults with
      moderate to severe asthma. BDP/formoterol HFA pMDI was noninferior to fixed
      combination budesonide/formoterol (the daily dosage of BDP was half that of
      budesonide) in terms of lung function, asthma symptoms and use of rescue
      medications in adults with moderate to severe asthma. BDP/formoterol HFA pMDI was
      also noninferior to, and had a faster onset of bronchodilation than, fixed
      combination fluticasone propionate/salmeterol. BDP/formoterol 200 microg/12
      microg per day or 400 microg/24 microg per day administered by the HFA pMDI was
      generally well tolerated. Moreover, a single high dose of BDP/formoterol (1000
      microg/60 microg) was generally well tolerated in patients with asthma.

PMID- 16906777
TI  - Targeting the epidermal growth factor receptor in the treatment of colorectal
      cancer: state of the art.
AB  - The epidermal growth factor receptor (EGFR) is an important mediator of normal
      cellular processes such as growth, survival, differentiation and morphogenesis.
      Disturbances in the EGFR pathway have been associated with the development and
      progression of malignancy, including cellular proliferation, angiogenesis,
      invasion/metastasis and anti-apoptosis, as well as with resistance to
      chemotherapy and/or radiation therapy. As a result, this is an excellent
      rationale for treatment with EGFR-specific therapeutic agents. These agents may
      be EGFR-targeted antibodies or small molecules that inactivate the receptor
      tyrosine kinase. While only cetuximab has received US FDA approval for the
      treatment of colorectal cancer, numerous agents are currently in development and
      in clinical trials and constitute an area of intensive, ongoing research.

PMID- 16906778
TI  - Pharmacological approaches to the management of cognitive dysfunction in
      schizophrenia.
AB  - Cognitive dysfunction is a core feature of schizophrenia as deficits that are
      present in the majority of patients with schizophrenia frequently precede the
      onset of other symptoms and persist even after other symptoms have been
      effectively treated. The use of atypical antipsychotics has produced some small
      improvements, although the need for adjunctive treatment specifically targeting
      cognitive dysfunction is gaining widespread acceptance. Animal models and some
      small clinical trials have yielded results that are promising but not definitive.
      Psychosocial interventions have also met with some success in ameliorating some
      cognitive limitations. The mixed results of pharmacological interventions are
      most likely to be as a result of a combination of methodological flaws of many
      studies, poor outcome measures, dose administration effects and problems with the
      agents themselves.

PMID- 16906782
TI  - Adalimumab: in psoriatic arthritis.
AB  - Adalimumab, a fully human monoclonal antibody, is a tumour necrosis factor
      antagonist that has been investigated for efficacy in psoriatic arthritis, based
      on well-established use of the drug in rheumatoid arthritis. In well-controlled
      Phase III trials, adalimumab (40 mg administered subcutaneously every other week)
      has shown efficacy in adult patients with psoriatic arthritis who had an
      inadequate response to previous treatment with NSAIDs (24-week ADEPT trial; n =
      313) or disease-modifying antirheumatic drugs (12-week study; n = 100). In these
      trials, adalimumab recipients experienced a significantly greater improvement in
      arthritis response (p < 0.001 in the ADEPT trial, and p <or= 0.05 in the smaller
      study) than placebo recipients, as assessed by the ACR20, ACR50 and ACR70
      response rates. There was radiographic evidence of progressive joint damage in
      the placebo group but not the adalimumab group at 24 weeks in the ADEPT trial,
      according to the mean total Sharp score modified for psoriatic arthritis. The
      signs and symptoms of psoriasis in patients with psoriatic arthritis were
      clinically and statistically more improved with adalimumab than with placebo,
      according to the PASI responses, at 12 and 24 weeks in the ADEPT trial (e.g.
      PASI50 rate 75% vs 12% at 24 weeks; p < 0.001). Adalimumab was generally well
      tolerated in clinical trials of psoriatic arthritis; the adverse event profile
      appears to be similar to that associated with use of the drug in rheumatoid
      arthritis.

PMID- 16906786
TI  - Efavirenz/emtricitabine/tenofovir disoproxil fumarate: triple combination tablet.
AB  - A new formulation combining fixed doses of the nucleoside reverse transcriptase
      inhibitors emtricitabine (200mg) and tenofovir disoproxil fumarate (tenofovir DF;
      300 mg) with the non-nucleoside reverse transcriptase inhibitor efavirenz (600
      mg) represents the first once-daily, one-tablet antiretroviral regimen. Co
      formulated efavirenz/emtricitabine/tenofovir DF demonstrated bioequivalence to
      concomitant administration of the individual agents in a pharmacokinetic trial in
      healthy volunteers (n = 48). Co-formulated efavirenz/emtricitabine/tenofovir DF
      has not been evaluated in clinical trials. However, a once-daily regimen of
      efavirenz, emtricitabine and tenofovir DF (administered as individual agents) was
      superior to once-daily efavirenz plus twice-daily co-formulated
      lamivudine/zidovudine in terms of virological suppression, immunological recovery
      and adverse events resulting in discontinuation of the study medications in a
      randomised, multicentre, noninferiority study in treatment-naive patients with
      HIV infection (n = 517). Both regimens are currently recommended as initial
      antiretroviral therapy. Preliminary data suggest that co-formulated
      efavirenz/emtricitabine/tenofovir DF, like the individual agents in combination
      with other antiretroviral drugs, is generally well tolerated. CNS adverse events,
      primarily headache and dizziness, were the most common treatment-emergent, drug
      related adverse events in the pharmacokinetic study involving the co-formulation.

PMID- 16906790
TI  - Photodynamic activity of substituted zinc trisulfophthalocyanines: role of plasma
      membrane damage.
AB  - We recently reported that variations in cellular phototoxicity among a series of
      alkynyl-substituted zinc trisulfophthalocyanines (ZnPcS3Cn) correlates with their
      hydrophobicity, with the most amphiphilic derivatives showing the highest cell
      uptake and phototoxicity. In this study we address the role of the plasma
      membrane in the photodynamic response as it relates to the overall hydrophobicity
      of the photosensitizer. The membrane tracker dye 1-[4(trimethylamino)phenyl]-6
      phenylhexa-1,3,5-triene (TMA-DPH), which is incorporated into plasma membranes by
      endocytosis, was used to establish plasma membrane uptake by EMT-6 cells of the
      ZnPcS3C, by colocalization, and TMA-DPH membrane uptake rates after photodynamic
      therapy were used to quantify membrane damage. TMA-DPH colocalization patterns
      show plasma membrane uptake of the photosensitizers after short 1 h incubation
      periods. TMA-DPH plasma membrane uptake rates after illumination of the
      photosensitizer-treated cells show a parabolic relationship with photosensitizer
      hydrophobicity that correlates well with the phototoxicity of the ZnPcS3C,. After
      a 1 h incubation period, overall phototoxicity correlates closely with the
      postillumination rate of TMA-DPH incorporation into the cell membrane, suggesting
      a major role of plasma membrane damage in the overall PDT effect. In contrast,
      after a 24 h incubation, phototoxicity shows a stronger but imperfect correlation
      with total cellular photosensitizer uptake rather than TMA-DPH membrane uptake,
      suggesting a partial shift in the cellular damage responsible for
      photosensitization from the plasma membrane to intracellular targets. We conclude
      that plasma membrane localization of the amphiphilic ZnPcS3C6-C9 is a major
      factor in their overall photodynamic activity.

PMID- 16906791
TI  - Rhodopsin deactivation is affected by mutations of Tyrl91.
AB  - The 9-methyl group of 11-cis retinal is important in the efficient formation of
      the active conformation of rhodopsin, Meta II. Here, Tyrl91 rhodopsin mutants
      were generated because of its proximity to that methyl group in the dark
      structure. If photoactivation results in movement of the 9-methyl group toward
      Tyrl91, the steric interactions involved with activation and/or deactivation
      might not be as tightly coupled in mutant proteins with smaller amino acids at
      that position. Tyrl91 mutations have no effect on the dark pigment. However,
      after photobleaching, the lifetime of Meta II is shorter; Meta II decays quickly
      into two inactive species: (1) a Meta III or Meta III-like species and (2) opsin
      and free retinal. The Meta III-like fraction maintains the covalent Schiff base
      linkage of the chromophore much longer than the wild type. On the other hand, the
      fast chromophore release is similar to cone pigments. Taken together, the data
      suggest that the role of the 9-methyl group after photo-isomerization is not only
      to form Meta II efficiently, but also to maintain its active conformation and
      allow for the timely hydrolysis of the Schiff base. Perturbation of this
      interaction effects changes in the hydrolysis of the Schiff base and for the case
      of the Y191A mutation the folded structure of the protein after photobleaching.

PMID- 16906789
TI  - Memantine: a review of its use in Alzheimer's disease.
AB  - Memantine (Ebixa, Axura, Namenda, Akatinol) is a moderate-affinity,
      uncompetitive, voltage-dependent, NMDA-receptor antagonist with fast on/off
      kinetics that inhibits excessive calcium influx induced by chronic
      overstimulation of the NMDA receptor. Memantine is approved in the US and the EU
      for the treatment of patients with moderate to severe dementia of the Alzheimer's
      type. In well designed clinical trials, oral memantine, as monotherapy or in
      addition to a stable dose of acetylcholinesterase inhibitors, was well tolerated
      during the treatment of mild to severe Alzheimer's disease for up to 52 weeks.
      Memantine generally modified the progressive symptomatic decline in global
      status, cognition, function and behaviour exhibited by patients with moderate to
      severe Alzheimer's disease in four 12- to 28-week trials. In patients with mild
      to moderate Alzheimer's disease, data from three 24-week trials are equivocal,
      although meta-analyses indicate beneficial effects on global status and
      cognition. Memantine is an effective pharmacotherapeutic agent, and currently the
      only approved option, for the treatment of moderate to severe Alzheimer's
      disease.

PMID- 16906792
TI  - Longitudinal diffusion of a polar tracer in the outer segments of rod
      photoreceptors from different species.
AB  - Vertebrate rod photoreceptors are the ultimate light sensors, as they can detect
      a single photon. In darkness, rods maintain a high concentration of the
      intracellular messenger cyclic guanosine monophosphate (cGMP), which binds to and
      keeps open cationic channels on the plasma membrane of the outer segment.
      Absorption of a photon by the visual pigment of the rod, rhodopsin, initiates a
      biochemical amplification cascade that leads to a reduction in the concentration
      of cGMP and closure of the channels, thereby converting the incoming light to an
      electrical signal. Because the absorption of a photon and the ensuing reactions
      are localized events, the magnitude of the response of the rod to a single photon
      depends on the spread of the decrease in the cGMP concentration along the length
      of the outer segment. The longitudinal diffusion of cGMP depends on the
      structural parameters of the rod outer segment, specifically the area and the
      volume available for diffusion. To characterize the effect of rod outer segment
      cytoarchitecture on diffusion, we have used fluorescence recovery after
      photobleaching (FRAP) and examined the mobility of a fluorescent polar tracer,
      calcein, in the rod outer segments from three species with different outer
      segment structures: frog (Rana pipiens), mouse (Mus musculus domesticus) and
      gecko (Gekko gekko). We found that the diffusion coefficient is similar for all
      three species, in the order of 8-17 microm(2) s(-1), in broad agreement with the
      predictions by Holcman and Korenbrot (Biophys. J. 2004:86;2566-2582) based on the
      known cytoarchitecture of rod outer segments. Consequently, the results also
      support their prediction that the longitudinal spread of light excitation in rods
      is similar across species.

PMID- 16906793
TI  - Phototropins and blue light-dependent calcium signaling in higher plants.
AB  - Plants have several kinds of photoreceptors, which regulate growth and
      development. Recent investigations using Arabidopsis thaliana revealed that the
      newly found blue light receptor phototropins mediate phototropism, chloroplast
      relocation, stomatal opening, rapid inhibition of hypocotyl elongation and leaf
      expansion. Several physiological studies suggest that one of the intermediates in
      phototropin signaling is cytosolic Ca2+. Studies using phototropin mutants have
      demonstrated that phototropins induce an increase in cytosolic Ca2+
      concentration. However, the function of Ca2+ in the phototropin-mediated
      signaling process remains largely unknown. This review presents findings about
      phototropin-mediated calcium mobilization and the involvement of calcium in blue
      light-dependent plant responses.

PMID- 16906794
TI  - Stabilization of membrane pores by packing.
AB  - We present a model for pore stabilization in membranes without surface tension.
      Whereas an isolated pore is always unstable (since it either shrinks, tending to
      reseal, or grows without bound until membrane disintegration), it is shown that
      excluded volume interactions in a system of many pores can stabilize individual
      pores of a given size in a certain range of model parameters. For such a
      multipore membrane system, the distribution of pore size and associated pore
      lifetime are calculated within the mean-field approximation. We predict that,
      above the temperature T(m), when the effective line tension becomes negative, the
      membrane exhibits a dynamic sievelike porous structure.

PMID- 16906795
TI  - Self-consistent mode-coupling approach to one-dimensional heat transport.
AB  - In the present Rapid Communication we present an analytical and numerical
      solution of the self-consistent mode-coupling equations for the problem of heat
      conductivity in one-dimensional systems. Such a solution leads us to propose a
      different scenario to accommodate the known results obtained so far for this
      problem. More precisely, we conjecture that the universality class is determined
      by the leading order of the nonlinear interaction potential. Moreover, our
      analysis allows us to determine the memory kernel, whose expression puts on a
      more firm basis the previously conjectured connection between anomalous heat
      conductivity and anomalous diffusion.

PMID- 16906796
TI  - Orientation selection in lamellar phases by oscillatory shears.
AB  - In order to address the selection mechanism that is responsible for the unique
      lamellar orientation observed in block copolymers under oscillatory shears, we
      use a constitutive law for the dissipative part of the stress tensor that
      respects the uniaxial symmetry of a lamellar phase. An interface separating two
      domains oriented parallel and perpendicular to the shear is shown to be
      hydrodynamically unstable, a situation analogous to the thin layer instability of
      stratified fluids under shears. The resulting secondary flows break the
      degeneracy between the parallel and perpendicular lamellar orientation, leading
      to a preferred perpendicular orientation in certain ranges of parameters of the
      polymer and of the shear.

PMID- 16906797
TI  - Interfacial dynamics in transport-limited dissolution.
AB  - Various model problems of "transport-limited dissolution" in two dimensions are
      analyzed using time-dependent conformal maps. For diffusion-limited dissolution
      (reverse Laplacian growth), several exact solutions are discussed for the
      smoothing of corrugated surfaces, including the continuous analogs of "internal
      diffusion-limited aggregation" and "diffusion-limited erosion." A class of non
      Laplacian, transport-limited dissolution processes is also considered, which
      raises the general question of when and where a finite solid will disappear. In a
      case of dissolution by advection-diffusion, a tilted ellipse maintains its shape
      during collapse, as its center of mass drifts obliquely away from the background
      fluid flow, but other initial shapes have more complicated dynamics.

PMID- 16906798
TI  - Numerical simulation of the twist-grain-boundary phase of chiral liquid crystals.
AB  - We study the structure of the twist-grain-boundary phase of chiral liquid
      crystals by numerically minimizing the Landau-de Gennes free energy. We analyze
      the morphology of layers at the grain boundary, to better understand the
      mechanism of frustration between the smectic layer order and chirality. As the
      chirality increases, the layer compression energy strongly increases while the
      effective layer bending rigidity is reduced due to unlocking of the layer
      orientation and the director. This results in large deviation of the layer
      morphology from that of Scherk's first minimal surface and linear stack of screw
      dislocations.

PMID- 16906799
TI  - Effects of disorder on a smectic--nematic phase transition.
AB  - Using x-ray scattering, we have studied the nematic to smectic- phase transition
      of the liquid crystal butyloxybenzilidene-octylaniline confined in an aerosil
      network. We find that the disorder introduced by the aerosil network destroys the
      long-range nature of the phase transition, and that the transition becomes
      similar to that observed in a finite-size system, with finite low-temperature
      correlation lengths of the ordered moments and a power-law behavior of the order
      parameter with respect to the reduced temperature observable in a limited
      temperature range. We also show evidence for a systematic evolution of the
      effective order parameter critical exponent beta with increasing disorder.

PMID- 16906800
TI  - Particles held by springs in a linear shear flow exhibit oscillatory motion.
AB  - The dynamics of small spheres that are held by linear springs in a low Reynolds
      number shear flow at neighboring locations is investigated. The flow elongates
      the beads, and the interplay of the shear gradient with the nonlinear behavior of
      the hydrodynamic interaction among the spheres causes in a large range of
      parameters a bifurcation to a surprising oscillatory bead motion. The parameter
      ranges wherein this bifurcation is either super- or subcritical are determined.

PMID- 16906801
TI  - Suppression of Winfree turbulence under weak spatiotemporal perturbation.
AB  - Winfree turbulence is a chaotic wave pattern developing through negative-tension
      instability of scroll wave filaments in three-dimensional weak excitable media.
      Here, we investigate the response of Winfree turbulence to a spatiotemporal
      forcing in the form of a traveling-wave modulation of the medium excitability. It
      is shown that turbulent waves can be suppressed much more rapidly by this method,
      in comparison with the space-uniform modulation of the medium excitability. Since
      the occurrence of Winfree turbulence is currently regarded as one of the possible
      mechanisms underlying cardiac fibrillation, this method turns out to be
      suggestive of a possible low-amplitude defibrillation approach.

PMID- 16906802
TI  - Pure multiplicative stochastic resonance of a theoretical anti-tumor model with
      seasonal modulability.
AB  - Pure multiplicative noise-induced stochastic resonance, which appears in an anti
      tumor system modulated by a seasonal external field, is studied by using
      theoretical analyses of the generalized potential and numerical simulations. For
      optimally selected values of the multiplicative noise intensity stochastic
      resonance is observed, which is manifested by the quasisymmetry of two potential
      minima. Theoretical results and numerical simulations are in good quantitative
      agreement.

PMID- 16906803
TI  - Thermally activated escape rate for a Brownian particle in a tilted periodic
      potential for all values of the dissipation.
AB  - The translational Brownian motion of a particle in a tilted washboard potential
      is considered. The dynamic structure factor and longest relaxation time are
      evaluated from the solution of the governing Langevin equation by using the
      matrix continued fraction method. The longest relaxation time is compared with
      the Kramers theory of the escape rate of a Brownian particle from a potential
      well as extended to the Kramers turnover region by Mel'nikov [Physics Reports
      209, 1 (1991)]. It is shown that in the low temperature limit, the universal
      Mel'nikov expression for the escape rate provides a good estimate of the longest
      relaxation time for all values of dissipation including the very low damping
      (VLD), very high damping (VHD), and turnover regimes. For low barriers (where the
      Mel'nikov method is not applicable) and zero tilt, analytic equations for the
      relaxation times in the VLD and VHD limits are derived.

PMID- 16906804
TI  - High-frequency effects in the FitzHugh-Nagumo neuron model.
AB  - The effect of a high-frequency signal on the FitzHugh-Nagumo excitable model is
      analyzed. We show that the firing rate is diminished as the ratio of the high
      frequency amplitude to its frequency is increased. Moreover, it is demonstrated
      that the excitable character of the system, and consequently the firing activity,
      is suppressed for ratios above a given threshold value. In addition, we show that
      the vibrational resonance phenomenon turns up for sufficiently large noise
      strength values.

PMID- 16906806
TI  - Generalized Langevin equation with fractional derivative and long-time
      correlation function.
AB  - We investigate the motion of a particle governed by a generalized Langevin
      equation with fractional derivative, nonlocal dissipative force, and long-time
      correlation function. We derive general expressions for the variances with a
      linear external force. We also analyze their asymptotic behaviors for the power
      law correlation function without external force.

PMID- 16906805
TI  - Anomalous heat conductivity induced by finite size and non-Markovian dynamics.
AB  - Heat conduction in a one-dimensional non-Markovian damping channel between two
      heat baths separated by a finite distance is studied numerically. It is found
      that the Fourier heat law is not obeyed for a finite-size underdamped channel
      under a Gaussian white noise and the coefficient of heat conductivity is a
      nonmonotonic function of the channel length in the sub-Ohmic damping case. The
      key dynamic feature is that the system does not approach the stationary state
      when it arrives at the cold bath for the former, and the system exhibits
      different diffusive behaviors from ballistic diffusion to subdiffusion at initial
      and asymptotic periods of time for the latter. We evaluate a damping-dependent
      critical separation size between two heat baths above which the heat conductivity
      becomes independent of the separation.

PMID- 16906807
TI  - Effective classical partition functions with an improved time-dependent reference
      potential.
AB  - The original Feynman-Kleinert [Phys. Rev. A 34, 5080 (1986)] variational approach
      to Euclidean path integrals is improved by introducing a reference harmonic
      potential whose center is allowed to change with time. The motion of the center
      of the potential is varied such that the "effective potential" of Feynman and
      Kleinert is minimized and leads to an equation of motion for the classical path
      in the reference system that closely reproduces the "exact" average path. The
      formalism is applied to the double-well potential V(x)=-x(2)/2 + gx(4)/4+1/4g.
      This modification improves the accuracy of the approximate quantum-mechanical
      distribution function and, to a larger extent, the density matrix.

PMID- 16906808
TI  - Energy barrier scalings in driven systems.
AB  - Energy landscape mappings are performed for two different molecular systems under
      mechanical loads. Barrier heights are observed to scale as Delta U approximately
      delta(3/2), where delta is a residual load. Catastrophe theory predicts that this
      scaling should arise for vanishing delta; however, this region is irrelevant in
      physical processes at finite temperature because thermal fluctuations cause the
      system to cross over the barrier before reaching the small-delta regime.
      Surprisingly, we find that the Delta U approximately delta(3/2), scaling is valid
      far beyond the vanishing delta regime described by catastrophe theory. We discuss
      how this scaling will therefore be relevant at finite temperatures and gives
      corrections to Eyring's theory for transition rates.

PMID- 16906809
TI  - Escape through an unstable limit cycle: resonant activation.
AB  - We consider a Brownian particle acted on by a linear conservative force, a
      nonlinear frictional force, and multiplicative colored and additive white noises;
      the frictional force can be negative when the external energy supply is large
      enough. We numerically calculate the mean first passage time (MFPT) for the
      particle to escape from an unstable limit cycle and find resonant activation,
      i.e., the MFPT first decreases, followed by a rise after passing through a
      minimum with increasing noise correlation time tau for a fixed noise variance.
      For fixed noise strength of the multiplicative noise the MFPT increases linearly
      with tau. This is in sharp contrast to the case of fluctuations of nonlinear
      potentials, in which the MFPT first increases nonlinearly before reaching a
      limiting value. Our model could be useful for understanding some biological
      processes.

PMID- 16906810
TI  - Distance versus energy fluctuations and electron transfer in single protein
      molecules.
AB  - Stochastic nature due to distance and energy fluctuations of single protein
      molecules involved in electron-transfer (ET) reactions is studied. Distance
      fluctuations have been assumed previously for causing the slow fluctuations in
      the ET rates between a donor-acceptor pair constrained to a native protein.
      Although the observed t(-1/2) power law can be derived using Langevin dynamics
      with a simple chain model, some discrepancies exist. The friction coefficient and
      the Rouse segment time constant deduced from experimental data are several orders
      of magnitude too large, even though the extracted force constant is reasonable.
      Therefore, questions are raised about the distance-fluctuation mechanism and the
      activationless ET hypothesis. As an alternative mechanism, we considered
      fluctuations in activation energy and analyzed the data from two different single
      protein experiments to determine spectral distribution of energy fluctuations.

PMID- 16906811
TI  - Pathways of activated escape in periodically modulated systems.
AB  - We investigate dynamics of activated escape in periodically modulated systems.
      The trajectories followed in escape form diffusion-broadened tubes, which are
      periodically repeated in time. We show that these tubes can be directly observed
      and find their shape. Quantitatively, the tubes are characterized by the
      distribution of trajectories that, after escape, pass through a given point in
      phase space for a given modulation phase. This distribution may display several
      peaks separated by the modulation period. Analytical results agree with the
      results of simulations of a Brownian particle in a model modulated potential.

PMID- 16906812
TI  - Molecular dynamics comparative study of Lennard-Jones -6 and exponential -6
      potentials: application to real simple fluids (viscosity and pressure).
AB  - In this work, using molecular dynamics simulation, the viscosity (dynamic
      property) and the pressure (static property) of spherical fluid particles
      interacting through Lennard-Jones -6 and exponential -6 potentials are computed.
      Simulations are performed for going from 10 to 20 for the Lennard-Jones potential
      and from 12 to 22 for the exponential one. Six different thermodynamic states are
      tested that cover a large range of conditions, from sub- to supercritical
      temperature and from low to high density. To compare in a consistent manner the
      results for the various potentials tested, the simulations are carried out for
      the same set of reduced thermodynamic conditions (using the critical point). It
      is found that a perfect corresponding-states formulation is not possible between
      these potentials. Then, these potentials are applied on real simple fluids
      (argon, oxygen, nitrogen, methane, ethane, and one mixture, air) and the
      calculated viscosity and pressure values are compared with reference values. It
      appears that, using the appropriate , both potential families lead to a good
      accuracy in pressure and viscosity using the same set of molecular parameters for
      both properties, the average absolute deviations being always lower than 5% for
      the studied states. In addition, it is shown that the exponential potential
      results do not outperform the Lennard-Jones ones. Furthermore, for all compounds
      except for methane, the best results are obtained for the Lennard-Jones 12-6 and
      the exponential 14-6 potentials. This result partly explains why, despite no
      theoretical background, the Lennard-Jones 12-6 potential is so widely used.
      Finally, it is shown that a van der Waals one-fluid model performs extremely well
      for the studied mixture (air).

PMID- 16906813
TI  - Universality of one-dimensional heat conductivity.
AB  - We show analytically that the heat conductivity of oscillator chains diverges
      with system size N as N(1/3), which is the same as for one-dimensional fluids.
      For long cylinders, we use the hydrodynamic equations for a crystal in one
      dimension. This is appropriate for stiff systems such as nanotubes, where the
      eventual crossover to a fluid only sets in at unrealistically large . Despite the
      extra equation compared to a fluid, the scaling of the heat conductivity is
      unchanged. For strictly one-dimensional chains, we show that the dynamic
      equations are those of a fluid at all length scales even if the static order
      extends to very large . The discrepancy between our results and numerical
      simulations on Fermi-Pasta-Ulam chains is discussed.

PMID- 16906814
TI  - Collective acoustic modes as renormalized damped oscillators: unified description
      of neutron and x-ray scattering data from classical fluids.
AB  - In the Q range where inelastic x-ray and neutron scattering are applied to the
      study of acoustic collective excitations in fluids, various models of the dynamic
      structure factor S(Q, omega) generalize in different ways the results obtained
      from linearized-hydrodynamics theory in the Q-->0 limit. Here we show that the
      models most commonly fitted to experimental S(Q, omega) spectra can be given a
      unified formulation. In this way, direct comparisons among the results obtained
      by fitting different models become now possible to a much larger extent than
      ever. We also show that a consistent determination of the dispersion curve and of
      the propagation Q range of the excitations is possible, whichever model is used.
      We derive an exact formula which describes in all cases the dispersion curve and
      allows for the first quantitative understanding of its shape, by assigning
      specific and distinct roles to the various structural, thermal, and damping
      effects that determine the Q dependence of the mode frequencies. The emerging
      picture describes the acoustic modes as Q-dependent harmonic oscillators whose
      characteristic frequency is explicitly renormalized in an exact way by the
      relaxation processes, which also determine, through the widths of both the
      inelastic and the elastic lines, the whole shape of collective-excitation
      spectra.

PMID- 16906815
TI  - Structure of molecular liquids: cavity and bridge functions of the hard spheroid
      fluid.
AB  - We present methodologies for calculating the direct correlation function c(1,2),
      the cavity function y(1,2), and the bridge function b(1,2), for molecular
      liquids, from Monte Carlo simulations. As an example we present results for the
      isotropic hard spheroid fluid with elongation e = 3. The simulation data are
      compared with the results from integral equation theory. In particular, we solve
      the Percus-Yevick and hypernetted chain equations. In addition, we calculate the
      first two terms in the virial expansion of the bridge function and incorporate
      this into the closure. At low densities, the bridge functions calculated by
      theory and from simulation are in good agreement, lending support to the
      correctness of our numerical procedures. At higher densities, the hypernetted
      chain results are brought into closer agreement with simulation by incorporating
      the approximate bridge function, but significant discrepancies remain.

PMID- 16906816
TI  - Shear-induced crystallization of a dense rapid granular flow: hydrodynamics
      beyond the melting point.
AB  - We investigate shear-induced crystallization in a very dense flow of monodisperse
      inelastic hard spheres. We consider a steady plane Couette flow under constant
      pressure and neglect gravity. We assume that the granular density is greater than
      the melting point of the equilibrium phase diagram of elastic hard spheres. We
      employ a Navier-Stokes hydrodynamics with constitutive relations all of which
      (except the shear viscosity) diverge at the crystal-packing density, while the
      shear viscosity diverges at a smaller density. The phase diagram of the steady
      flow is described by three parameters: an effective Mach number, a scaled energy
      loss parameter, and an integer number m: the number of half-oscillations in a
      mechanical analogy that appears in this problem. In a steady shear flow the
      viscous heating is balanced by energy dissipation via inelastic collisions. This
      balance can have different forms, producing either a uniform shear flow or a
      variety of more complicated, nonlinear density, velocity, and temperature
      profiles. In particular, the model predicts a variety of multilayer two-phase
      steady shear flows with sharp interphase boundaries. Such a flow may include a
      few zero-shear (solidlike) layers, each of which moving as a whole, separated by
      fluidlike regions. As we are dealing with a hard sphere model, the granulate is
      fluidized within the "solid" layers: the granular temperature is nonzero there,
      and there is energy flow through the boundaries of the solid layers. A linear
      stability analysis of the uniform steady shear flow is performed, and a plausible
      bifurcation diagram of the system, for a fixed m, is suggested. The problem of
      selection of m remains open.

PMID- 16906817
TI  - Pattern selection by a granular wave in a rotating drum.
AB  - The results of an experimental investigation of granular segregation in a thin
      rotating drum are presented. A mechanism based on the presence of an uphill wave
      of particles has been found to govern the observed pattern of petals.
      Specifically we develop a simple model that captures the essential physics of the
      segregation and yields an algebraic expression that predicts the number of petals
      in the pattern.

PMID- 16906818
TI  - Measurements of the yield stress in frictionless granular systems.
AB  - We perform extensive molecular dynamics simulations of two-dimensional
      frictionless granular materials to determine whether these systems can be
      characterized by a single static yield shear stress. We consider boundary-driven
      planar shear at constant volume and either constant shear force or constant shear
      velocity. Under steady flow conditions, these two ensembles give similar results
      for the average shear stress versus shear velocity. However, near jamming it is
      possible that the shear stress required to initiate shear flow can differ
      substantially from the shear stress required to maintain flow. We perform several
      measurements of the shear stress near the initiation and cessation of flow. At
      fixed shear velocity, we measure the average shear stress Sigma(yv) in the limit
      of zero shear velocity. At fixed shear force, we measure the minimum shear stress
      Sigma(yf) required to maintain steady flow at long times. We find that in finite
      size systems Sigma(yf) > Sigma(yv), which implies that there is a jump
      discontinuity in the shear velocity from zero to a finite value when these
      systems begin flowing at constant shear force. However, our simulations suggest
      that the difference Sigma(yf) - Sigma(yv), and thus the discontinuity in the
      shear velocity, tend to zero in the infinite-system-size limit. Thus, our results
      imply that in the large-system limit, frictionless granular systems can be
      characterized by a single static yield shear stress. We also monitor the short
      time response of these systems to applied shear and show that the packing
      fraction of the system and shape of the velocity profile can strongly influence
      whether or not the shear stress at short times overshoots the long-time average
      value.

PMID- 16906819
TI  - Granular fountains: convection cascade in a compartmentalized granular gas.
AB  - This paper extends the two-compartment granular fountain [D. van der Meer, P.
      Reimann, K. van der Weele, and D. Lohse, Phys. Rev. Lett. 92, 184301 (2004)] to
      an arbitrary number of compartments: the tendency of a granular gas to form
      clusters is exploited to generate spontaneous convective currents, with particles
      going down in the well-filled compartments and going up in the diluted ones. We
      focus upon the bifurcation diagram of the general -compartment system, which is
      constructed using a dynamical flux model and which proves to agree quantitatively
      with results from molecular dynamics simulations.

PMID- 16906820
TI  - Thermal collapse of a granular gas under gravity.
AB  - Free cooling of a gas of inelastically colliding hard spheres represents a
      central paradigm of kinetic theory of granular gases. At zero gravity the
      temperature of a freely cooling homogeneous granular gas follows a power law in
      time. How does gravity, which brings inhomogeneity, affect the cooling? We
      combine molecular dynamics simulations, a numerical solution of hydrodynamic
      equations and an analytic theory to show that a granular gas cooling under
      gravity undergoes thermal collapse: it cools down to zero temperature and
      condenses on the bottom of the container in a finite time.

PMID- 16906822
TI  - Layering in sedimentation of suspensions of charged colloids: simulation and
      theory.
AB  - We study the equilibrium sediment of a multicomponent system of charged colloids
      using primitive model Monte Carlo simulations, which include counterions
      explicitly. We find separation of the different colloidal components into almost
      pure layers, where colloids with large charge-to-mass ratio sediment higher in
      the sample. This effect appears due to a competition between ionic entropy,
      gravitational energy, and electrostatic energy. Our simulations provide a direct
      confirmation of recent theoretical predictions on the sedimentation of
      multicomponent mixtures of charged colloids in regimes with relatively low total
      densities and low colloidal charges. To explore the limitations of the theory we
      perform simulations at higher total densities for monodisperse and multicomponent
      systems and at stronger electrostatic couplings by increasing the colloidal
      charge for monodisperse suspensions. We find good agreement between theory and
      simulation when the colloidal charge is increased in the monodisperse case.
      However, we find deviations between simulations and theory upon increasing the
      total densities in the monodisperse and multicomponent systems. The density
      profiles obtained from simulations are more homogeneous than those predicted by
      theory. The spontaneous formation of layered structures predicted by the theory
      and found by simulation can serve as a useful tool to separate different
      components from a mixture of charged colloids.

PMID- 16906821
TI  - Heterogeneities and topological defects in two-dimensional pinned liquids.
AB  - We simulate a model of repulsively interacting colloids on a commensurate two
      dimensional triangular pinning substrate where the amount of heterogeneous motion
      that appears at melting can be controlled systematically by turning off a
      fraction of the pinning sites. We correlate the amount of heterogeneous motion
      with the average topological defect number, time-dependent defect fluctuations,
      colloid diffusion, and the form of the van Hove correlation function. When the
      pinning sites are all off or all on, the melting occurs in a single step. When a
      fraction of the sites are turned off, the melting becomes considerably broadened
      and signatures of a two-step melting process appear. The noise power associated
      with fluctuations in the number of topological defects reaches a maximum when
      half of the pinning sites are removed and the noise spectrum has a pronounced 1 /
      f(alpha) structure in the heterogeneous regime. We find that regions of high
      mobility are associated with regions of high dislocation densities.

PMID- 16906823
TI  - Geometrical confinements and depletion interactions.
AB  - In the system with two large spheres confined between two parallel plates, there
      are depletion interactions between the two large spheres and between one large
      sphere and the closely placed plate. Obviously, the depletion interactions
      exerted on one large sphere will be strongly affected by the presence of the
      closely placed plate or the other large sphere. This prediction is confirmed by
      the numerical results obtained through the acceptance ratio method (ARM) or
      density integration method (DIM), i.e., they are strengthened when two large
      spheres are contacted. Furthermore, it is found that the influences on the
      depletion forces are also sensitive to the angle of the centers' connection line
      between the two large spheres and the confining walls. In addition, the numerical
      results show that the total depletion force exerted on one large sphere from both
      the other large sphere and the closely placed plate can be determined through ARM
      or DIM from the interactions between the two large spheres or between one large
      sphere and the corresponding closely placed plate.

PMID- 16906824
TI  - Flow of foam past an elliptical obstacle.
AB  - To investigate the link between discrete small-scale and continuous large scale
      mechanical properties of a foam, we observe its two-dimensional flow in a
      channel, around an elliptical obstacle. We measure the drag, lift, and torque
      acting on the ellipse versus the angle between its major axis and the flow
      direction. The drag increases with the spanwise dimension, in marked contrast
      with a square obstacle. The lift passes through a smooth extremum at an angle
      close to, but smaller than 45 degrees. The torque peaks at a significantly
      smaller angle 26 degrees. No existing model can reproduce the observed viscous,
      elastic, plastic behavior. We propose a microscopic visco-elasto-plastic model
      which agrees qualitatively with the data.

PMID- 16906825
TI  - Thermoreversible gelation is a Bose-Einstein condensation.
AB  - On the basis of the classical tree statistics, being combined with the lattice
      theory of a polymer solution, we prove that within the mean-field approximation
      thermoreversible gelation of polyfunctional molecules is a third order phase
      transition analogous to the Bose-Einstein condensation of ideal Bose gases. The
      derivative of the osmotic compressibility with respect to the concentration of
      primary functional molecules is shown to reveal a discontinuity at the sol/gel
      transition point, whose width is directly related to the amplitude of the
      divergent term in the weight-average molecular weight of clusters. An inclusion
      of cycle formation, as well as concentration fluctuations, may, however, change
      the nature of the phase transition.

PMID- 16906826
TI  - Critical behavior of entropic shear rigidity.
AB  - We report on extensive molecular dynamics (MD) simulations of a model for gels in
      both two and three dimensions. The model consists of randomly cross-linked
      monomers with a concentration p of cross-links above the percolation
      concentration so that the system is in the amorphous solid phase. As the
      concentration of cross-links approaches the percolation concentration, the
      entropic shear modulus vanishes as G approximately(p-p(c))(t) with t
      approximately 1.9 in three dimensions and t approximately 1.3 in two dimensions.
      These results hold whether or not the background fluid consisting of finite
      clusters is retained in the system. These results are also consistent with our
      previous calculations and with a conjecture of de Gennes but not with recent
      analytical results and another body of simulations.

PMID- 16906827
TI  - Critical behavior in colloid-polymer mixtures: theory and simulation.
AB  - We extensively investigated the critical behavior of mixtures of colloids and
      polymers via the two-component Asakura-Oosawa model and its reduction to a one
      component colloidal fluid using accurate theoretical and simulation techniques.
      In particular the theoretical approach, hierarchical reference theory [A. Parola
      and L. Reatto, Adv. Phys. 44, 211 (1995)], incorporates realistically the effects
      of long-range fluctuations on phase separation giving exponents which differ
      strongly from their mean-field values, and are in good agreement with those of
      the three-dimensional Ising model. Computer simulations combined with finite-size
      scaling analysis confirm the Ising universality and the accuracy of the theory,
      although some discrepancy in the location of the critical point between one
      component and full-mixture description remains. To assess the limit of the pair
      interaction description, we compare one-component and two-component results.

PMID- 16906828
TI  - Effect of simple shear on liquid drainage within foams.
AB  - This paper examines the impact of shear on the drainage of liquid through a foam.
      The effect on drainage of changes in the Plateau border network brought about by
      shear is examined. This effect of shear was modeled using both a detailed three
      dimensional simulation of foam structure, and an idealized two-dimensional
      hexagonal foam. The main phenomenon that has been discovered is that shear
      induces an anisotropy in the drainage of liquid through the foam. If the foam is
      strained and liquid flows under gravity either perpendicular or parallel to the
      shear direction, a net liquid flow in the direction perpendicular to the
      direction of gravity is induced. It was found that the degree of anisotropy
      increases nearly linearly with increasing strain until the foam yields, after
      which the degree of flow anisotropy remains roughly constant. This is not a small
      effect, with the flow in the direction perpendicular to gravity being up to about
      20% of the flow in the direction of gravity at the yield strain. This shear
      induced anisotropy provides a potential explanation for the hitherto puzzling
      phenomenon of the convective roll in foam. The other two effects examined are the
      effect of shear on the length of Plateau borders per volume of foam, which
      increases as strain increases, and the resistance of the foam to flow in the
      direction of gravity, which increases if the strain direction is perpendicular to
      gravity, but decreases if the strain is parallel to gravity.

PMID- 16906829
TI  - Brownian-drag induced particle current in a model colloidal system.
AB  - We numerically study the behavior of a collection of overdamped Brownian
      particles in a channel, in the presence of a flow field applied on similar but
      slower particles in a wide chamber in contact with the channel. For a suitable
      range of shear rates, we find that the flow field induces a unidirectional drift
      in the confined particles, and is stronger for narrower channels. The average
      drift velocity initially rises with increasing shear rate, then shows saturation
      for a while, thereafter starts decreasing, in qualitative agreement with recent
      theoretical studies [Phys. Rev. B 70, 205423 (2004)] based on Brownian drag and
      "loss of grip." Interestingly, if the sign of the interspecies interaction is
      reversed, the direction of the induced drift remains the same, but the flow rate
      at which loss of grip occurs is lower, and the level of fluctuations is higher.

PMID- 16906830
TI  - Correlated fluctuations of microparticles in viscoelastic solutions: quantitative
      measurement of material properties by microrheology in the presence of optical
      traps.
AB  - The Brownian motions of microscopic particles in viscous or viscoelastic fluids
      can be used to measure rheological properties. This is the basis of recently
      developed one- and two-particle microrheology techniques. For increased temporal
      and spatial resolution, some microrheology techniques employ optical traps, which
      introduce additional forces on the particles. We have systematically studied the
      effect that confinement of particles by optical traps has on their auto- and
      cross-correlated fluctuations. We show that trapping causes anticorrelations in
      the motion of two particles at low frequencies. We demonstrate how these
      anticorrelations depend on trap strength and the shear modulus of viscoelastic
      media. We present a method to account for the effects of optical traps, which
      permits the quantitative measurement of viscoelastic properties in one- and two
      particle microrheology over an extended frequency range in a variety of viscous
      and viscoelastic media.

PMID- 16906831
TI  - Correlations and fluctuations in phase coarsening.
AB  - Three-dimensional phase coarsening at various volume fractions is simulated by
      employing multiparticle diffusion methods. The dynamic process of phase
      coarsening is visualized through a three-dimensional movie. The present study
      also characterizes interparticle spacings in polydispersed particle systems and
      clarifies the controversial mathematical expressions for interparticle spacings
      used in the literature for 30 years. Consequently, this study reveals spatial,
      temporal, and nearest-neighbor correlations in polydispersed particle systems. A
      new three-dimensional movie of a Voronoi network demonstrating these correlations
      is provided. Our simulation and experiments show that growth rates of individual
      particles deviate from those of the mean-field theory, which is caused by their
      differing local environments. Multiplicative noise provides a good basis to
      describe the stochastic nature of fluctuations during phase coarsening.

PMID- 16906832
TI  - Dynamics of liquid silica as explained by properties of the potential energy
      landscape.
AB  - The dynamics of silica displays an Arrhenius temperature dependence, classifying
      silica as a strong glass-former. Using recently developed concepts to analyze the
      potential energy landscape, one can get a far-reaching understanding of the long
      range transport of silica. It can be expressed in terms of properties of the
      thermodynamics as well as local relaxation processes, thereby extending the
      phenomenological standard picture of a strong glass-former. The local relaxation
      processes are characterized by complex correlated sequences of bond breaking and
      reformation processes.

PMID- 16906833
TI  - Thermodynamic and dynamic anomalies for dumbbell molecules interacting with a
      repulsive ramplike potential.
AB  - Using collision driven discrete molecular dynamics, we investigate the
      thermodynamics and dynamics of systems of 500 dumbbell molecules interacting by a
      purely repulsive ramplike discretized potential, consisting of n steps of equal
      size. We compare the behavior of the two systems, with n=18 and n=144 steps. Each
      system exhibits both thermodynamic and dynamic anomalies, a density maximum and
      the translational and rotational mobilities show anomalous behavior. Starting
      with very dense systems and decreasing the density, both mobilities first
      increase, reach a maximum, then decrease, reach a minimum, and finally increase;
      this behavior is similar to the behavior of SPC/E (Simple Point Charge-Extended)
      water. The regions in the pressure-temperature plane of translational and
      rotational mobility anomalies depend strongly on n. The product of the
      translational diffusion coefficient and the orientational correlation time
      increases with temperature, in contrast with the behavior of most liquids.

PMID- 16906834
TI  - Hybrid Monte Carlo simulation of a glass-forming binary mixture.
AB  - We propose a different, hybrid Monte Carlo algorithm that combines
      configurational bias particle swaps with parallel tempering. We use this
      algorithm to simulate a standard model of a glass-forming binary mixture above
      and below the so-called mode-coupling temperature T(MCT). We find that an ansatz
      that was used previously to extrapolate thermodynamic quantities to temperatures
      below T(MCT) breaks down in the vicinity of the mode-coupling temperature. We
      also find that the Adam-Gibbs relations D(alpha)exp(-a/TS(c)) and
      tau(alpha)exp(b/TS(c)), which connect the diffusion coefficient D and the
      relaxation time tau with the configurational entropy S(c), are valid for all
      temperatures for which the configurational and vibrational contributions to the
      free energy decouple.

PMID- 16906835
TI  - Wetting-induced depletion interaction between particles in a phase-separating
      liquid mixture.
AB  - Inclusion of solid particles drastically affects the pattern evolution of phase
      separation of a binary fluid mixture, via preferential wetting of one of the
      phases to the particles. Here we study this problem by numerical simulation,
      which incorporates interparticle hydrodynamic interactions properly. When
      particles favor one of the components of a mixture, wetting layers are quickly
      formed on the particle surfaces and all particles are eventually included into
      the more wettable phase. For immobile particles, domains of the more wettable
      phase are pinned to the particles and the domain growth is thus suppressed. For
      this case, the domain size at a certain phase-separation time decreases
      monotonically with increasing the particle concentration. For mobile particles,
      on the other hand, the reentrant morphological transformation is observed as a
      function of the particle concentration: With an increase in the particle
      concentration, the domain morphology of the more wettable phase sequentially
      changes from network, droplet to network. We found that the final morphological
      transition is induced by wetting-induced depletion interaction: strong attractive
      interactions act among particles when the total volume of the more wettable phase
      is not enough to cover all the particles by wetting layers.

PMID- 16906836
TI  - Metastable liquid-liquid coexistence and density anomalies in a core-softened
      fluid.
AB  - Linearly sloped or "ramp" potentials belong to a class of core-softened models
      which possess a liquid-liquid critical point (LLCP) in addition to the usual
      liquid-gas critical point. Furthermore, they exhibit thermodynamic anomalies in
      their density and compressibility, the nature of which may be akin to those
      occurring in water. Previous simulation studies of ramp potentials have focused
      on just one functional form, for which the LLCP is thermodynamically stable. In
      this work we construct a series of ramp potentials, which interpolate between
      this previously studied form and a ramp-based approximation to the Lennard-Jones
      (LJ) potential. By means of Monte Carlo simulation, we locate the LLCP, the first
      order high density liquid (HDL)-low density liquid (LDL) coexistence line, and
      the line of density maxima for a selection of potentials in the series. We
      observe that as the LJ limit is approached, the LLCP becomes metastable with
      respect to freezing into a hexagonal close packed crystalline solid. The
      qualitative nature of the phase behavior in this regime shows a remarkable
      resemblance to that seen in simulation studies of accurate water models.
      Specifically, the density of the liquid phase exceeds that of the solid; the
      gradient of the metastable LDL-HDL line is negative in the pressure (p)
      temperature (T) plane; while the line of density maxima in the p-T plane has a
      shape similar to that seen in water and extends into the stable liquid region of
      the phase diagram. As such, our results lend weight to the "second critical
      point" hypothesis as an explanation for the anomalous behavior of water.

PMID- 16906838
TI  - Local velocity measurements in heterogeneous and time-dependent flows of a
      micellar solution.
AB  - We present and discuss the results of pointwise velocity measurements performed
      on a viscoelastic micellar solution made of cetyltrimethylammonium bromide and
      sodium salicylate in water, respectively, at the concentrations of 50 and 100
      mmol. The sample is contained in a Couette device and subjected to flow in the
      strain controlled mode. This particular solution shows shear banding and, in a
      narrow range of shear rates at the right end of the stress plateau, apparent
      shear thickening occurs. Time-dependent recordings of the shear stress in this
      range reveal that the flow has become unstable and that large sustained
      oscillations of the shear stress and of the first normal stresses difference
      emerge and grow in the flow. Local pointwise velocity measurements clearly reveal
      a velocity profile typical of shear banding when the imposed shear rate belongs
      to the plateau, but also important wall slip in the entire range of velocity
      gradients investigated. In the oscillations regime, the velocity is recorded as a
      function of time at a fixed point close to the rotor of the Couette device. The
      time-dependent velocity profile reveals random fluctuations but, from time to
      time, sharp decreases much larger than the standard deviation are observed. An
      attempt is made to correlate these strong variations with the stress oscillations
      and a correlation coefficient r is computed. However, the small value found for
      the coefficient r does not allow us to draw a final conclusion as concerns the
      correlation between stress oscillations and velocity fast decreases.

PMID- 16906837
TI  - Relaxation rate in the critical dynamics of the micellar isobutoxyethanol-water
      system with lower consolute point.
AB  - For the isobutoxyethanol-water mixture of critical composition acoustical scaling
      function measurements have been performed at frequencies between 200 kHz and 3
      MHz. Using the relaxation rates of concentration fluctuations as resulting from
      dynamic light scattering and shear viscosity measurements, the acoustical data
      can be well represented by the Bhattacharjee-Ferrell empirical scaling function.
      The theoretically predicted scaled half attenuation frequency Omega(BF)(1/2)=2.1
      follows from the experiments. However, the adiabatic coupling constant, derived
      from the amplitude of the Bhattacharjee-Ferrell critical term, displays an
      unreliably strong temperature dependence. It is shown that this dependence upon
      temperature likely reflects a hidden low-frequency and low amplitude relaxation
      term in the acoustical spectra of the mixture of critical composition.

PMID- 16906839
TI  - Structural transitions of the mono-olein bicontinuous cubic phase induced by
      inclusion of protein lysozyme solutions.
AB  - Inclusion of protein lysozyme molecules in the lipidic mono-olein cubic phase
      induces a transition from a Pn3m structure to an Im3m one. The small-angle x-ray
      scattering method with high-intensity synchrotron radiation enabled us to follow
      closely the transition depending on the conditions of lysozyme solutions. We show
      that concentrated lysozyme solutions induced the appearance of the Im3m structure
      coexisting with the Pn3m structure. From the relation between the lattice
      parameters of these two structures it is shown that they are related by the
      Bonnet transformation of the underlying triply periodic minimal surfaces. We
      found that the transition also occurred at lower lysozyme concentration when NaCl
      induced an attraction between lysozyme molecules. The origin of the transition
      was considered as a frustration in the cubic phase where lysozyme molecules were
      highly confined. A simple estimation of the frustration was given, which took
      into account the translational entropy of lysozyme molecules. At the highest
      concentration of lysozyme and NaCl the Im3m structure was found to disappear and
      left only the Pn3m structure. This was probably either due to the crystallization
      or phase separation of lysozyme solutions ongoing microscopically, which absorbed
      lysozyme molecules from channels of the cubic phase and thus removed the
      frustration.

PMID- 16906840
TI  - Theory for solvent, momentum, and energy transfer between a surfactant solution
      and a vapor atmosphere.
AB  - We develop a complete set of equations governing the evolution of a sharp
      interface separating a volatile-solvent/nonvolatile-surfactant solution from a
      vapor atmosphere. In addition to a sorption isotherm equation and the
      conventional balances for mass, linear momentum, and energy, these equations
      include an alternative to the Hertz-Knudsen-Langmuir equation familiar from
      conventional theories of evaporation and condensation. This additional equation
      arises from a consideration of configurational forces within a thermodynamical
      framework. While the notion of configurational forces is well developed and
      understood for the description of materials that, like crystalline solids,
      possess natural reference configurations, very little has been done regarding
      their role in materials, such as viscous fluids, that do not possess preferred
      reference states. We therefore provide comprehensive developments of
      configurational forces, the balance of configurational momentum, and
      configurational thermodynamics. Our treatment does not require a choice of
      reference configuration. The general evolution equations arising from our theory
      account for the thermodynamic structure of the solution and the interface and for
      sources of dissipation related to the transport of surfactant, momentum, and heat
      in the solution and within the interface along with the transport of solute,
      momentum, kinetic energy, and heat across the interface. Moreover, the equations
      account for the Soret and Dufour effects in the solution and on the interface and
      for observed discontinuities of the temperature and chemical potential across the
      interface. Due to the complexity of these equations, we provide approximate
      equations which we compare to equations preexistent in the literature.

PMID- 16906841
TI  - Growth of bimolecular films of three-tailed amphiphiles.
AB  - The three-tailed amphiphile ferric stearate molecule, which forms a bimolecular
      layer on water surface with molecules in the lower and upper layers in different
      conformations, has been studied to understand transfer and growth of bimolecular
      films on the surface of hydrophilic silicon substrates. This bimolecular film
      forms a two-dimensional lattice on water with a slightly distorted hexagonal
      lattice where both the in-plane and out-of-plane domain sizes are small. The film
      also showed larger microscopic rigidity compared to its macroscopic mechanical
      response. This asymmetric bimolecular layer was found to be preserved when the
      film is transferred on the substrates at different values of surface pressures
      ranging from 1 mN/m to near-collapse (55 mN/m). Both the upper and lower layers
      become denser and interfaces between these layers become sharper with increase in
      deposition pressure but the growths have different natures. The lower layer of
      transferred film is dense from 1 mN/m and, except for a steplike increase between
      20 and 30 mN/m, changes slowly in density. The density of the upper molecular
      layer grows continuously with surface pressure.

PMID- 16906842
TI  - Boundary dynamics of the sweeping interface.
AB  - A boundary dynamics of sweeping interface is proposed to describe the interface
      that sweeps space to collect distributed material. Based upon geometrical
      consideration on a simple physical process representing a certain experiment, the
      dynamics is formulated as the small diffusion limit of the Mullins-Sekerka
      problem of crystal growth. It is demonstrated that a steadily extending finger
      solution exists for a finite range of propagation speed, but numerical
      simulations suggest they are unstable and the interface shows a complex time
      development.

PMID- 16906843
TI  - Theoretical and experimental optical studies of cholesteric liquid crystal films
      with thermally induced pitch gradients.
AB  - The reflection properties of cholesteric films with thermally induced pitch
      gradients are theoretically and experimentally studied. It is shown that the
      optical behavior of such films corresponds to the averaged contribution of a
      number of stochastic pitch variation profiles, due to the transversal and
      longitudinal nonuniformities that develop in the helical structure of such
      samples. Depending on the annealing time, both narrow-band and broadband behavior
      can be selectively achieved. The influence of the pitch profile gradient on the
      broadband reflection performance of cholesteric samples is theoretically
      analyzed, and a multi-slab structure for achieving optimum efficiency is
      proposed.

PMID- 16906844
TI  - Dielectric relaxation in chevron surface stabilized ferroelectric liquid
      crystals.
AB  - The dielectric response of surface stabilized ferroelectric liquid crystals with
      chevron layer structure is studied within low and intermediate frequency ranges,
      characteristic for collective molecular excitations. By analytically solving the
      dynamic equation for collective molecular fluctuations under a weak alternating
      electric field, it is demonstrated that chevron cells stabilized by both nonpolar
      and polar surface interactions undergo at medium frequencies two Debye relaxation
      processes, connected with two chevron slabs, on opposite sides of the interface
      plane. This result is confirmed, experimentally, making use of the electro-optic
      technique. Based on qualitative arguments supported by microscopic observations
      of zigzag defects at different frequencies and amplitudes of the external
      electric field, it is shown that, at low frequencies, the electro-optic response
      of chevron samples is determined by three kinds of motions of zigzag walls. The
      first two dynamic categories are related to collective relaxation processes at
      weak fields, within smectic A layers forming zigzag walls, and drift or creep
      motions of thick walls occurring at stronger field amplitudes. Dynamic processes
      of the third kind correspond to sliding of zigzag walls, which appear at yet
      stronger field amplitudes, but below the switching threshold.

PMID- 16906845
TI  - Isotropic-nematic interface in suspensions of hard rods: mean-field properties
      and capillary waves.
AB  - We present a study of the isotropic-nematic interface in a system of hard
      spherocylinders. First we compare results from Monte Carlo simulations and
      Onsager density functional theory for the interfacial profiles of the
      orientational order parameter and the density. Those interfacial properties that
      are not affected by capillary waves are in good agreement, despite the fact that
      Onsager theory overestimates the coexistence densities. Then we show results of a
      Monte Carlo study of the capillary waves of the interface. In agreement with
      recent theoretical investigations [Elgeti and Schmid, Eur. Phys. J. E 18, 407
      (2005)] we find a strongly anisotropic capillary wave spectrum. For the wave
      numbers accessed in our simulations, the spectrum is quadratic, i.e., elasticity
      does not play a role. We conjecture that this effect is due to the strong bending
      rigidity of the director field in suspensions of spherocylinders.

PMID- 16906846
TI  - NMR angle-dependent spectral study of core dynamics in a discotic columnar phase.
AB  - A detailed (2)H NMR study of a discotic monomer is reported in its columnar phase
      at 61.4 MHz. A simulation of angular-dependent spectral patterns and/or signal
      intensities of the aromatic deuterons is shown to provide information on the
      small step (or jump) diffusion rates in the low temperature region of the D(ho)
      phase, where the motion is in the intermediate motion regime. In the high end of
      this phase, the motion falls into the fast motion regime and spectral patterns
      become insensitive to the diffusion rate. In such a case, angular-dependent NMR
      signal intensities were used to give the required dynamic information. The
      diffusive motion about the columnar axis is found to be thermally activated with
      an activation energy of 69 kJ/mol. Deuteron spin-lattice relaxation rates were
      measured at 61.4 MHz and interpreted by a conventional rotational diffusion model
      in order to complement and compare with the above study when possible.

PMID- 16906847
TI  - Role of initial conditions in the decay of spatially periodic patterns in a
      nematic liquid crystal.
AB  - The decay of stripe patterns in planarly aligned nematic liquid crystals has been
      studied experimentally and theoretically. The initial patterns have been
      generated by the electrohydrodynamic instability and a light diffraction
      technique has been used to monitor their decay. In our experiments different
      decay rates have been observed as a function of the pattern wave number.
      According to our theoretical analysis they belong to a spectrum of decay modes
      and are individually selected in dependence on the initial conditions. Additional
      insight has emerged from a refined physical optical description of the
      diffraction intensity. The results compare well with experiments, which include
      also controlled modifications of the initial conditions to assess different decay
      modes.

PMID- 16906848
TI  - Power law relaxation and glassy dynamics in Lebwohl-Lasher model near the
      isotropic-nematic phase transition.
AB  - Orientational dynamics in a liquid crystalline system near the isotropic-nematic
      (IN) phase transition is studied using molecular dynamics simulations of the well
      known Lebwohl-Lasher model. As the IN transition temperature is approached from
      the isotropic side, we find that the decay of the orientational time correlation
      functions (OTCF) slows down noticeably, giving rise to a power law decay at
      intermediate time scales. The angular velocity time correlation function also
      exhibits a rather pronounced power law decay near the IN boundary. In the mean
      squared angular displacement at comparable time scales, we observe the emergence
      of a subdiffusive regime which is followed by a superdiffusive regime before the
      onset of the long-time diffusive behavior. We observe signature of dynamical
      heterogeneity through pronounced non-Gaussian behavior in orientational motion
      particularly at lower temperatures. This behavior closely resembles what is
      usually observed in supercooled liquids. We obtain the free energy as a function
      of orientational order parameter by the use of the transition matrix Monte Carlo
      method. The free energy surface is flat for the system considered here and the
      barrier between isotropic and nematic phases is vanishingly small for this weakly
      first-order phase transition, hence allowing large scale, collective, and
      correlated orientational density fluctuations. This might be responsible for the
      observed power law decay of the OTCFs.

PMID- 16906849
TI  - Thermomechanical oscillations in hybrid nematic liquid crystals.
AB  - Thermomechanical oscillations observed previously in hybrid oriented nematic
      liquid crystals (NLCs) are explained theoretically. The effect is conditioned by
      the hydrodynamic flow tendency to reduce the curvature of the "flexible ribbon"
      of hybrid NLCs. There is qualitative agreement between the theoretical
      calculations and the experimental results.

PMID- 16906850
TI  - Simple model for biaxial smectic-A liquid-crystal phases.
AB  - We have generalized the McMillan theory of liquid crystalline smectic order in
      uniaxial particle fluids to biaxial particles. Upon varying the control
      parameter, a uniaxial nematic phase may: (i) order biaxially first, then
      smectically; (ii) order smectically first, then biaxially; and (iii)
      simultaneously order biaxially and smectically. We investigate, in the limit of
      complete orientational order of the molecular major axes, which of these
      scenarios are realized for a simple model of particles with the symmetry of
      rectangular parallelepipeds. We also present a generic variational derivation of
      the theory based on the identification of the dominant order parameters for the
      most ordered phase.

PMID- 16906851
TI  - Changes in molecular dynamics upon formation of a polymer dispersed liquid
      crystal.
AB  - The molecular dynamics during the formation of a polymer dispersed liquid crystal
      (PDLC) was followed by dielectric relaxation spectroscopy in the frequency range
      from 10(-1) to 2 x 10(6) Hz and over the temperature range from 158 to 273 K. The
      composite was produced by thermal polymerization induced phase separation of a
      mixture of triethyleneglycol dimethacrylate and the nematic liquid crystal, E7,
      in the proportion of 60:40 w/w. Both monomer and liquid crystal vitrify upon
      cooling having glass transition relaxation processes already characterized by
      some of us; yet E7 was previously studied in a narrower frequency range, so the
      present work updates its dielectric behavior. The starting mixture exhibits a
      rather complex dielectric spectrum due to the detection of multiple processes
      occurring simultaneously in the monomer and liquid crystal constituents. The PDLC
      formation occurs by mobility changes essentially in the liquid crystal tumbling
      motion, while the main relaxation of the monomer depletes upon polymerization. A
      low intense secondary process of E7 hardly detected in the bulk material is
      enhanced in both starting mixture and final composite allowing its
      characterization.

PMID- 16906852
TI  - Robustness of the periodic and chaotic orientational behavior of tumbling nematic
      liquid crystals.
AB  - The dynamical behavior of molecular alignment strongly affects physical
      properties of nematic liquid crystals. A theoretical description can be made by a
      nonlinear relaxation equation of the order parameter and leads to the prediction
      that rather complex even chaotic orientational behavior occur. Here the influence
      of fluctuating shear rates on the orientational dynamics especially on chaotic
      solutions is discussed. With the help of phase portraits and time evolution
      diagrams, we investigated the influence of different fluctuation strengths on the
      flow aligned, isotropic, and periodic solutions. To explore the effect of
      fluctuations on the chaotic behavior, we calculated the largest Lyapunov exponent
      for different fluctuation strengths. We found in all cases that small
      fluctuations of the shear rate do not affect the basic features of the dynamics
      of tumbling nematics. Furthermore, we present an amended potential modeling the
      isotropic to nematic transition and discuss the equivalence and difference to the
      commonly used Landau-de Gennes potential. In contrast to the Landau-de Gennes
      potential, our potential has the advantage to restrict the order parameter to
      physically admissible values. In the case of extensional flow, we show that the
      amended potential leads for increasing extensional rate to a better agreement
      with experimental results.

PMID- 16906853
TI  - Molecular dynamic study of the odd-even effect in some 4-n-alkyl-4'
      cyanobiphenyls.
AB  - Using a united atom model, we performed molecular dynamics (MD) simulations on
      the 4-n-alkyl-4'-cyanobiphenyl (nCB) liquid crystal homologous series for at a
      constant reduced temperature in the nematic phase. To evaluate the rotational
      diffusion coefficient (RDC), the second- and fourth-rank order parameters (OP's)
      and correlation time were calculated from MD trajectories. We analyzed the
      rotational viscosity coefficient (RVC) by using the Nemtsov-Zakharov and
      Fialkowski methods based on statistical-mechanical approaches. The simulated RDC,
      RVC, and OP's were found to be reasonable when compared with previous theoretical
      and experimental data. These quantities were also calculated for the rigid core
      and alkyl chain segments separately for each mesogen, to take a closer look at
      the molecule tail-chain flexibility. The properties calculated for a rigid core
      were compared with those for an alkyl chain, and satisfactory results were
      obtained. Odd-even effects for RDF, RVC, and molecular ordering parameters were
      calculated for five mesogens.

PMID- 16906854
TI  - Modified models of polymer phase separation.
AB  - In this paper we discuss continuum models of phase separation in polymer
      solutions, with emphasis on the thermodynamic foundation of these models. We
      demand that these models obey a free energy dissipation relation, which in the
      present context plays the role of the second law of thermodynamics, since the
      system is isothermal. First, we derive a modified two-fluid model for
      viscoelastic phase separation from nonequilibrium thermodynamics. Then we study
      the special case when only diffusion is present, and hydrodynamic effects are
      neglected. Numerical results demonstrate that our models show better stability
      properties and at the same time reproduce the expected physical phenomena such as
      volume shrinking and phase inversion. Our findings suggest that these important
      phenomena are caused by a diffusional asymmetry of the constituent molecules.

PMID- 16906855
TI  - Crossover from reptation to Rouse dynamics in a one-dimensional model.
AB  - A simple one-dimensional model is constructed for polymer motion. It exhibits the
      crossover from reptation to Rouse dynamics through gradually allowing hernia
      creation and annihilation. The model is treated by the density matrix technique
      which permits an accurate finite-size-scaling analysis of the behavior of long
      polymers.

PMID- 16906856
TI  - Kinetics of disorder-to-fcc phase transition via an intermediate bcc state.
AB  - Time-resolved small-angle x-ray scattering measurements reveal that a long-lived
      intermediate bcc state forms when a poly(styrene-b-isoprene) diblock copolymer
      solution in an isoprene selective solvent is rapidly cooled from the disordered
      micellar fluid at high temperature to an equilibrium fcc state. The kinetics of
      the epitaxial growth of the [111] fcc peak from the [110] bcc peak was obtained
      by fitting the scattering data to a simple model of the transformation. The
      growth of the [111] fcc peak agrees with the Avrami model of nucleation and
      growth kinetics with an exponent n=1.4, as does the initial decay of the [110]
      bcc peak, with an exponent n=1.3. The data were also found to be in good
      agreement with the Cahn model of grain boundary nucleation and growth.

PMID- 16906857
TI  - Early-stage roughening of the polymer-polymer interface approaching the glass
      transition temperature by real-time neutron reflection.
AB  - The early-stage roughening of the interface between thin deuterated poly(methyl
      methacrylate) (d-PMMA) layers on thick polystyrene (PS) films was studied as a
      function of the temperature using real-time specular neutron reflectivity. By
      measuring the growth of the interface roughness as a precursor of the dewetting,
      the characteristic time constant of the early stages of the process was studied
      as a function of the temperature approaching the glass transition temperature
      (T(g)) of the two polymers from above and compared with the prediction of the
      growth of the interface by the spinodal process. Both solid and liquid regimes
      were probed, in which the viscosity of the thin film or the substrate dominates
      respectively. The characteristic growth time of the process also depends on the
      upper film thickness to a power of 5 or 6 in the solid or liquid regimes,
      respectively, as predicted by the theory of spinodal dewetting.

PMID- 16906858
TI  - Orientational order parameter of the nematic liquid crystalline phase of F-actin.
AB  - We measured the orientational order parameter of F-actin traversing the isotropic
      nematic phase transition using a combination of techniques, including
      fluorescence imaging, local birefringence measurements, and small-angle x-ray
      scattering. The order parameter approaches a saturated value of 0.75 for actin
      concentrations above the region of the isotropic-nematic phase transition. This
      result implies a significant extent of misalignment and consequently entanglement
      among long actin filaments, even in the nematic phase. We determine the specific
      birefringence of completely aligned F-actin to be Deltan(0)=2.3 x 10(-5) ml/mg.
      At concentrations slightly below the isotropic-nematic transition, nonzero values
      of the order parameter are detected for hours following an initial alignment,
      indicating extremely slow rotational kinetics of F-actin in the entangled
      networks.

PMID- 16906859
TI  - Electrostatics of charged dielectric spheres with application to biological
      systems.
AB  - Because electrostatic forces are crucial in biological systems, molecular
      dynamics simulations of biological systems require a method of computing
      electrostatic forces that is accurate and rapid. We propose a surface charge
      method, apply it to a system of arbitrary number of charged dielectric spheres,
      and obtain an exact solution for an arbitrary configuration of the spheres. The
      precision depends only on the number of terms kept in a series expansion and can
      therefore be controlled at will. It appears that the first few terms are usually
      adequate. The exact result exhibits a phenomenon that we call asymmetric
      screening. Namely, the magnitude of attractive interactions is decreased
      (relative to point charges in an infinite solvent) while the magnitude of
      repulsive interactions is increased (again, relative to point charges in an
      infinite solvent). This effect might aid in the adoption of correct conformations
      and in intermolecular recognition. Evaluation of the energy involves only matrix
      inversion. The surface charge method can be transformed easily to a numerical
      method for use with arbitrary surfaces. With modest additions, the model also
      describes an electrorheological fluid. Such a system provides the cleanest
      opportunity to apply the model.

PMID- 16906860
TI  - Protein design based on the relative entropy.
AB  - An approach to protein design is proposed based on the relative entropy and a
      reduced amino acid alphabet. In this approach, the relative entropy is used as a
      minimization object function. The method has been tested on a real protein's off
      lattice model successfully, and the results are similar to those obtained from
      other design studies. It can be applied as a uniform frame for both folding and
      inverse folding of protein. An iterative calculation method of the ensemble
      average of the contact strength is proposed at the same time.

PMID- 16906861
TI  - Localized activity profiles and storage capacity of rate-based autoassociative
      networks.
AB  - We study analytically the effect of metrically structured connectivity on the
      behavior of autoassociative networks. The steady state equations are derived for
      a generic input-output function, and then we focus on their solutions in the case
      of networks composed of three alternative simple rate-based model neurons:
      threshold-linear, binary or smoothly saturating units. For a connectivity which
      is short range enough the threshold-linear network shows localized retrieval
      states. The saturating and binary models also exhibit spatially modulated
      retrieval states if the highest activity level that they can achieve is above the
      maximum activity of the units in the stored patterns. We show that this
      saturation level together with the linear gain of the transfer function are
      important parameters that determine the possibility of localized retrieval. If
      the ratio of the number of stored patterns to the number of connections per unit
      goes to zero, while the latter goes to infinity, it is possible to derive an
      analytical formula for the critical value of the connectivity width, below which
      one observes spatially nonuniform retrieval states. The formula is also shown to
      offer a good first approximation for higher storage loads. We show that even in
      the case of localized retrieval the storage capacity remains proportional to the
      number of connections per neurons, with the proportionality constant lower by a
      factor of 3-4 compared to uniform retrieval. The approach that we present here is
      generic in the sense that there are no specific assumptions on the single unit
      input-output function nor on the exact connectivity structure.

PMID- 16906862
TI  - Thermodynamic features characterizing good and bad folding sequences obtained
      using a simplified off-lattice protein model.
AB  - The thermodynamics of the small SH3 protein domain is studied by means of a
      simplified model where each beadlike amino acid interacts with the others through
      a contact potential controlled by a random matrix. Good folding sequences,
      characterized by a low native energy, display three main thermodynamical
      ensembles, namely, a coil-like ensemble, an unfolded globule, and a folded
      ensemble (plus two other states, frozen and random coils, populated only at
      extreme temperatures). Interestingly, the unfolded globule has some regions
      already structured. Poorly designed sequences, on the other hand, display a wide
      transition from the random coil to a frozen state. The comparison with the
      analytic theory of heteropolymers is discussed.

PMID- 16906863
TI  - Antireliability of noise-driven neurons.
AB  - We demonstrate, within the framework of the FitzHugh-Nagumo model, that a firing
      neuron can respond to a noisy driving in a nonreliable manner: the same Gaussian
      white noise acting on identical neurons evokes different patterns of spikes. The
      effect is characterized via calculations of the Lyapunov exponent and the event
      synchronization correlations. We construct a theory that explains the
      antireliability as a combined effect of a high sensitivity to noise of some
      stages of the dynamics and nonisochronicity of oscillations. Geometrically, the
      antireliability is described by a random noninvertible one-dimensional map.

PMID- 16906864
TI  - Dynamics of vascular branching morphogenesis: the effect of blood and tissue
      flow.
AB  - Vascularization of embryonic organs or tumors starts from a primitive lattice of
      capillaries. Upon perfusion, this lattice is remodeled into branched arteries and
      veins. Adaptation to mechanical forces is implied to play a major role in
      arterial patterning. However, numerical simulations of vessel adaptation to
      haemodynamics has so far failed to predict any realistic vascular pattern. We
      present in this article a theoretical modeling of vascular development in the
      yolk sac based on three features of vascular morphogenesis: the disconnection of
      side branches from main branches, the reconnection of dangling sprouts ("dead
      ends"), and the plastic extension of interstitial tissue, which we have observed
      in vascular morphogenesis. We show that the effect of Poiseuille flow in the
      vessels can be modeled by aggregation of random walkers. Solid tissue expansion
      can be modeled by a Poiseuille (parabolic) deformation, hence by deformation
      under hits of random walkers. Incorporation of these features, which are of a
      mechanical nature, leads to realistic modeling of vessels, with important
      biological consequences. The model also predicts the outcome of simple mechanical
      actions, such as clamping of vessels or deformation of tissue by the presence of
      obstacles. This study offers an explanation for flow-driven control of vascular
      branching morphogenesis.

PMID- 16906865
TI  - Adhesion of membranes via switchable molecules.
AB  - Biomimetic membranes that adhere to a solid substrate or another interface via
      switchable crosslinker molecules are studied theoretically using analytical
      methods and Monte Carlo simulations. The flexible crosslinkers exhibit two
      conformations which have a different end-to-end distance and, thus, lead to
      different local separations of the membrane from the substrate surface.
      Transitions between the molecular conformations can be induced by light, electric
      potential, or changes in pH and lead to active shape fluctuations of the membrane
      and, thus, to an increased membrane roughness. The forward and backward
      transitions are characterized by two transition rates, omega(+) and omega(-),
      respectively, which define the average fraction X=omega(+) /(omega(+) + omega(-))
      of + (or on) states and the mean switching rate omega = (omega(+) + omega(-)) /
      2. The membrane roughness is explicitly calculated as a function of X and omega.
      It is shown that the interplay of active and thermal fluctuations is subtle and
      that it is, in general, not possible to describe the active fluctuations in terms
      of an effective temperature.

PMID- 16906866
TI  - Phonon dispersion of oriented DNA by inelastic x-ray scattering.
AB  - Films of oriented deoxyribonucleic acid (DNA), prepared by the wet spinning
      method, have been studied using inelastic x-ray scattering. Spectra were recorded
      within the range of energy transfers -30< homega <30 meV at momentum transfers
      homegaQ ranging from 2.5 to 30 nm(-1) whereby the direction of Q essentially
      coincided with the helical axis. Measurements at ambient temperature cover
      samples in the A, B, C, and D conformations of DNA. Within the limits of the
      instrumental resolution, the spectra were analyzed by the response of a damped
      harmonic oscillator delivering dispersion and damping of modes having
      displacements with nonzero projections onto Q, i.e., essentially the compression
      waves traveling along the helical axis. The longitudinal speed of sound resulting
      from the sinusoidal dispersion varies only weakly with conformation. Our sound
      speed values are compared to results from Brillouin spectroscopy. The dispersion
      curves exhibit a minimum at about the inverse rise per residue, which -- together
      with strong elastic scattering -- reflect the large degree of disorder.
      Overdamping of the modes is observed for Q>5 nm(-1). The possibility that the
      observed large damping parameters are due to several contributing modes is
      discussed in terms of a simple model calculation for an idealized double helix.
      Whereas the quasicrystalline approximation for an effective disordered chain
      could well describe the sinusoidal dispersion, it fails to reproduce the observed
      damping by one order of magnitude. Our results indicate that the high-frequency
      dynamics of DNA is liquidlike and is most appropriately described by
      instantaneous normal modes of short correlation length.

PMID- 16906867
TI  - Estimation of the input parameters in the Feller neuronal model.
AB  - The stochastic Feller neuronal model is studied, and estimators of the model
      input parameters, depending on the firing regime of the process, are derived.
      Closed expressions for the first two moments of functionals of the first-passage
      time (FTP) through a constant boundary in the suprathreshold regime are derived,
      which are used to calculate moment estimators. In the subthreshold regime, the
      exponentiality of the FTP is utilized to characterize the input parameters. The
      methods are illustrated on simulated data. Finally, approximations of the first
      passage-time moments are suggested, and biological interpretations and
      comparisons of the parameters in the Feller and the Ornstein-Uhlenbeck models are
      discussed.

PMID- 16906868
TI  - Respiratory patterns in oscine birds during normal respiration and song
      production.
AB  - In this work we study the generation of respiratory patterns by oscine birds. We
      present a model capable of generating realistic respiratory patterns, during
      normal respiration and song production. The model accounts for the interaction
      between neural nuclei and air sac dynamics. We performed experiments in vivo in
      order to test the predictions of the model, measuring air sac pressure during
      song and normal respiration in canaries (Serinus canaria).

PMID- 16906869
TI  - Topology of resultant networks shaped by evolutionary pressure.
AB  - Understanding the topology of complex systems abstracted to networks is important
      for unraveling their functional capabilities. Many such networks follow the small
      world and scale-free regimes. Several models of artificially growing networks
      lead to this observed network topology. Most previously proposed models for
      growing networks, such as rich-get-richer and duplication-divergence, produce
      realistic network topologies but do not consider the effects of exogenous forces
      such as optimization for adaptation in shaping network topology. It is likely
      that such forces have shaped complex systems throughout their evolution. To
      develop further insights into possible mechanisms that shape networks, a model
      that uses several previously proposed network growth algorithms was developed to
      grow networks that adapt under exogenous stress. A decision tree problem was used
      to generate a complex Boolean function. Growing networks were required to adapt
      to correctly decode this function using an evolutionary selection process. Under
      this growth regimen all growing network models are similarly adaptable. The newly
      added nodes tend to cluster into pathways emanating from few inputs, regardless
      of the growth algorithm. Distribution of redundant pathways from inputs to the
      output follow a power-law function with a scaling exponent (approximately 1.3).
      Similar distribution of redundant pathways was observed from inputs in a cell
      signaling network and an air traffic control network. A flat distribution of
      redundant pathways from inputs was observed in growing networks that do not
      attempt to adapt. This analysis provides initial insights into distribution of
      pathways in naturally evolving complex systems that have defined input-output
      relationships.

PMID- 16906870
TI  - Mechanics of nonplanar membranes with force-dipole activity.
AB  - A study is made of how active membrane proteins can modify the long wavelength
      mechanics of fluid membranes. The activity of the proteins is modelled as
      disturbing the protein surroundings through nonlocal force distributions of which
      a force-dipole distribution is the simplest example. An analytic expression
      describing how the activity modifies the force-balance equation for the membrane
      surface is obtained in the form of a moment expansion of the force distribution.
      This expression allows for further studies of the consequences of the activity
      for nonplanar membranes. In particular the active contributions to mechanical
      properties such as tension and bending moments become apparent. It is also
      explained how the activity can induce a hydrodynamic attraction between the
      active proteins in the membrane.

PMID- 16906871
TI  - Fluctuation spectrum of quasispherical membranes with force-dipole activity.
AB  - The fluctuation spectrum of a quasispherical vesicle with active membrane
      proteins is calculated. The activity of the proteins is modeled as the proteins
      pushing on their surroundings giving rise to nonlocal force distributions. Both
      the contributions from the thermal fluctuations of the active protein densities
      and the temporal noise in the individual active force distributions of the
      proteins are taken into account. The noise in the individual force distributions
      is found to become significant at short wavelengths.

PMID- 16906872
TI  - Buckling transition in icosahedral shells subjected to volume conservation
      constraint and pressure: relations to virus maturation.
AB  - Minimal energy shapes of closed, elastic shells with 12 pentagonal disclinations
      introduced in otherwise hexagonally coordinated crystalline lattice are studied.
      The geometry and the total energy of shells are studied as a function of the
      elastic properties of the material they are made of. Particular emphasis is put
      on the buckling transition of the shells, that is, a strong preference of the
      shell shapes to "buckle out" in spatial regions close to the pentagonal
      disclinations for a certain range of the elastic parameters of the problem. The
      transition effectively increases the mean square aspherity of shapes, making them
      look more like an icosahedron rather than a sphere, which is a preferred shape
      prior to the onset of the transition. The properties of the buckling transition
      are studied in cases when (i) the total volume enclosed by the elastic shell has
      to be fixed and when (ii) there is an internal pressure acting on the shell. This
      may be related to the maturation process in nonenveloped dsDNA viruses, where the
      insertion of the genetic material in a preformed protein shell (viral coating)
      may effectively impose the fixed volume and/or pressure constraint. Several
      scenarios that may explain the experimentally observed feature of mature viruses
      being more aspherical (facetted) from their immature precursors are discussed,
      and predictions for the elastic properties of viral coatings are obtained on the
      basis of the presented studies.

PMID- 16906875
TI  - Toy model of fractional transport of cancer cells due to self-entrapping.
AB  - A simple mathematical model is proposed to study the influence of cell fission on
      transport. The model describes fractional, in time, tumor development, which is a
      one-dimensional continuous-time random walk. The model is relevant for
      consideration of both solid and diffusive cancers.

PMID- 16906873
TI  - Stochastic model of intraflagellar transport.
AB  - We present a stochastic model of filament growth driven by the motor-assisted
      transport of particles along the filament. We show how the growth can be analyzed
      in terms of a sequence of first passage times for a particle hopping between the
      two ends of the filament, and use this to calculate the mean and variance of the
      length as a function of time. We determine how the growth depends on the waiting
      time density of the underlying hopping process, and highlight differences in the
      growth generated by normal and anomalous transport, for which the mean waiting
      time is finite and infinite, respectively. In the case of normal transport, we
      determine the length at which there is a balance between particle-driven assembly
      and particle-independent disassembly of the filament. The existence of such a
      balance point is thought to provide a mechanism for flagellar length control.

PMID- 16906874
TI  - Multiple extrema in the intermolecular potential and the phase diagram of protein
      solutions.
AB  - Recent experiments have revealed several surprising features of the phase
      equilibria in protein solutions: liquid-liquid phase separation which is, in some
      cases, metastable with respect to the liquid-solid equilibrium, and in others
      unobservable; widely varying crystallization enthalpies, including completely
      athermal crystallization; the co-existence of several crystalline polymorphs; and
      others. Other studies have shown that the solvent molecules at the hydrophobic
      and polar patches on the protein molecular surfaces are structured, introducing
      repulsive forces at surface separations equal to several water molecule sizes. In
      search of a causal link between the latter and former findings, we apply Monte
      Carlo simulation techniques in the investigation of phase diagrams associated
      with globular biological molecules in solution. We account for the solvent
      structuring via short-range isotropic two-body intermolecular potentials
      exhibiting multiple extrema. We show that the introduction of a repulsive maximum
      or a secondary attractive minimum at separations longer than the primary
      attractive minimum has dramatic effects on the phase diagram: liquid-liquid
      separation curves are driven to lower or higher temperatures, the sensitivity of
      the solubility curve (liquidus) to temperature, i.e., the enthalpy of
      crystallization, is significantly reduced or enhanced, metastable liquid-liquid
      separation may become stable and vice versa, and both low- and high-density
      crystalline phases are observed. The similarity of these features of the
      simulated phase behavior to those observed experimentally suggests that at least
      some of the mysteries of the protein phase equilibria may be due to the
      structuring of the solvent around the protein molecular surfaces. Another
      conclusion is that at least some of the dense liquids seen in protein solutions
      may be stable and not metastable with respect to a solid phase.

PMID- 16906876
TI  - Analytical model of magnetic nanoparticle transport and capture in the
      microvasculature.
AB  - An analytical model is presented for predicting the transport and capture of
      therapeutic magnetic nanoparticles in the human microvasculature. The
      nanoparticles, with surface bound drug molecules, are injected into the vascular
      system upstream from malignant tissue, and are captured at the tumor site using a
      local applied magnetic field. The applied field is produced by a rare-earth
      cylindrical magnet positioned outside the body. An analytical expression is
      derived for predicting the trajectory of a particle as it flows through the
      microvasculature in proximity to the magnet. In addition, a scaling relation is
      developed that enables the prediction of the minimum particle radius required for
      particle capture. The theory takes into account the dominant magnetic and fluidic
      forces, which depend on the position and properties of the magnet, the size and
      magnetic properties of the nanoparticles, the dimensions of the microvessel, the
      hematocrit level of the blood, and the flow velocity. The model is used to study
      noninvasive drug targeting, and the analysis indicates that submicron particles
      can be directed to tumors that are several centimeters from the field source.

PMID- 16906878
TI  - Weight matrices for protein-DNA binding sites from a single co-crystal structure.
AB  - Transcription-factor proteins bind to specific DNA sequences to regulate gene
      expression in cells. DNA-binding sites are often identified using weight matrices
      calculated from multiple known binding sites. However, in many cases the number
      of examples is limited. Here, we report on an atomistic method that starts from
      an x-ray co-crystal structure of the protein bound to one particular DNA
      sequence, and infers other binding sites, which are used to construct a weight
      matrix. The emphasis of the paper is on using the Wang-Landau Monte Carlo
      algorithm to efficiently sample high-affinity binding sites, which demonstrates
      that sampling can produce accurate weight matrices in analogy to bioinformatics
      approaches. For cases of low complexity, we compare to the exhaustive (but slow)
      dead-end elimination algorithm. To recover crystal binding sites, it is important
      to include bound water in the protein-DNA interface. Our approach can, in
      principle, even be applied when no native protein-DNA co-crystal structure is
      available, only the structure of a closely related homologous protein whose amino
      acid sequence is changed to the protein of interest.

PMID- 16906877
TI  - Stochastic explanation of speckle contrast detection in ultrasound-modulated
      optical tomography.
AB  - Ultrasound-modulated optical tomography is an imaging technique that detects
      ultrasonically tagged light in optically turbid media to obtain images with
      optical contrast and ultrasonic spatial resolution. A CCD-camera-based speckle
      contrast detection scheme has been introduced previously to detect modulated
      light emerging from the ultrasonic sample volume. Differences in speckle contrast
      were experimentally observed when ultrasound was applied compared to when it was
      not. In this paper we provide an analytic explanation for this phenomenon and
      connect speckle statistics with ultrasonic field parameters. The theory predicts
      that speckle contrast changes linearly with applied acoustic intensity. This
      prediction is experimentally validated for both 1 and ultrasound. Signal
      dependence on ultrasound frequency is discussed.

PMID- 16906879
TI  - DNA electrophoresis in microfluidic post arrays under moderate electric fields.
AB  - The dynamics of long DNA moving through microfluidic arrays of micron-sized posts
      under a moderate electric field are modeled by a Scher-Lax continuous-time random
      walk. The microscale model consists of a repetitive sequence of three steps: (i)
      collision with the post and extension into two arms, (ii) electric-field-driven
      unhooking from the post, and (iii) uniform translation until the next collision.
      The model features two random variables: the initial offset between the two arms
      of the polymer during a given collision and the distance traveled between
      collisions. For experimentally realistic values of the electric field strength
      and DNA molecular weight, scaling laws indicate that the chain will generally be
      in a stem-flower conformation when unhooking from the post. Compared to a taut
      chain model at the same field strength, the stem-flower conformation reduces the
      time engaged with the post and increases the collision frequency. Analytical
      expressions for the mean velocity and dispersivity are derived as a function of
      the post density, post spacing, free-solution mobility, Kuhn length, and sequence
      length. The incomplete extension of the chain does not strongly affect the mean
      velocity, but tends to increase the dispersivity relative to a taut chain. As a
      result, the separation resolution decreases as the field decreases for a moderate
      field, in agreement with experiments. The quantitative agreement between the
      model and experimental data is satisfactory, especially considering that the
      model contains no adjustable parameters.

PMID- 16906880
TI  - Frequency of elemental events of intracellular Ca(2+) dynamics.
AB  - The dynamics of intracellular Ca(2+) is driven by random events called Ca(2+)
      puffs, in which Ca(2+) is liberated from intracellular stores. We show that the
      emergence of Ca(2+) puffs can be mapped to an escape process. The mean first
      passage times that correspond to the stochastic fraction of puff periods are
      computed from a novel master equation and two Fokker-Planck equations. Our
      results demonstrate that the mathematical modeling of Ca(2+) puffs has to account
      for the discrete character of the Ca(2+) release sites and does not permit a
      continuous description of the number of open channels.

PMID- 16906881
TI  - Vortex formation by active agents as a model for Daphnia swarming.
AB  - We propose a self-propelled particle model for the swarming of Daphnia that takes
      into account mutual repulsion and attraction to a center. Surprisingly, a vortex
      is formed only for an intermediate strength of propulsion. The phase diagram and
      the transitions between states with and without a vortex are analyzed, and the
      nature of the phase boundaries is discussed based on a linear stability analysis
      of the motion of individual swimmers. This allows us to identify various key
      parameters determining the characteristic features of the collective motion.

PMID- 16906882
TI  - Selective advantage for sexual reproduction.
AB  - This paper develops a simplified model for sexual reproduction within the
      quasispecies formalism. The model assumes a diploid genome consisting of two
      chromosomes, where the fitness is determined by the number of chromosomes that
      are identical to a given master sequence. We also assume that there is a cost to
      sexual reproduction, given by a characteristic time tau(seek) during which
      haploid cells seek out a mate with which to recombine. If the mating strategy is
      such that only viable haploids can mate, then when tau(seek) = 0, it is possible
      to show that sexual reproduction will always out compete asexual reproduction.
      However, as tau(seek) increases, sexual reproduction only becomes advantageous at
      progressively higher mutation rates. Once the time cost for sex reaches a
      critical threshold, the selective advantage for sexual reproduction disappears
      entirely. The results of this paper suggest that sexual reproduction is not
      advantageous in small populations per se, but rather in populations with low
      replication rates. In this regime, the cost for sex is sufficiently low that the
      selective advantage obtained through recombination leads to the dominance of the
      strategy. In fact, at a given replication rate and for a fixed environment
      volume, sexual reproduction is selected for in high populations because of the
      reduced time spent finding a reproductive partner.

PMID- 16906883
TI  - Minimal model for tumor angiogenesis.
AB  - In this work, we show a mathematical model for the angiogenesis by endothelial
      cells. We present the model at the level of partial differential equations,
      describing the spatiotemporal evolution of the cell population, the extracellular
      matrix macromolecules, the proteases, the tumor angiogenic factors, and the
      possible presence of inhibitors. We mainly focus, however, on a complementary,
      more physiologically realistic, hybrid approach in which the cells are treated as
      individual particles. We examine the model numerically in two-dimensional
      settings, discussing its comparison with experimental results.

PMID- 16906884
TI  - Glauber model in a quantum representation.
AB  - The Glauber model is reconsidered based on a quantum formulation of the master
      equation. Unlike the conventional approach the temperature and the Ising energy
      are included from the beginning by introducing a Heisenberg-like picture of the
      second quantized operators. This method enables us to get an exact expression for
      the transition rate of a single flip process w(i)(sigma(i)) which is in
      accordance with the principle of detailed balance. The transition rate differs
      significantly from the conventional one due to Glauber in the low-temperature
      regime. Here the behavior is controlled by the Ising energy and not by the
      microscopic time scale.

PMID- 16906885
TI  - Cell aggregation: packing soft grains.
AB  - Cellular aggregates may be considered as collections of membrane enclosed units
      with a pressure difference between the internal and external liquid phases. Cells
      are kept together by membrane adhesion and/or confined space compression. Pattern
      formation and, in particular, intercellular spacing have important roles in
      controlling solvent diffusion within such aggregates. A physical approach is used
      to study generic aspects of cellular packings in a confined space. Average
      material properties are derived from the free energy. The appearance of
      penetrating intercellular void channels is found to be critically governed by the
      cell wall adhesion mechanisms during the formation of dense aggregates. A fully
      relaxed aggregate efficiently hinders solvent diffusion at high hydrostatic
      pressures, while a small fraction (approximately 0.1) of adhesion related packing
      frustration is sufficient for breaking such a blockage even at high a pressure.

PMID- 16906886
TI  - Nonlinear dynamics induced in liquid crystals in the presence of the orbital and
      spin angular momentum of light.
AB  - We studied the dynamical effects induced in a homeotropic nematic film when a
      normally incident circularly polarized light beam with an elliptical intensity
      profile is used. A three-dimensional dynamical model shows that, besides the
      spin, the orbital angular momentum of photons also plays a role in the
      reorientation process. Our measurements fairly reproduce the main dynamical
      features predicted by the model in the near threshold region. The model, however,
      does not work, as it is, at higher incident laser power where chaotic director
      rotation was reported [A. Vella, A. Setaro, B. Piccirillo, E. Santamato, Phys.
      Rev. E 67, 051704 (2003)].

PMID- 16906887
TI  - Corresponding states in nematic elasticity.
AB  - A comparative study of the temperature dependence of the elastic constants of the
      nematic liquid crystals known as PAA (p-azoxyanisole), MBBA 4'-methoxybenzylidene
      4-n-butylaniline, and 5CB (4-n-pentyl-4'-cyanobiphenyl) will be made in this
      work. After a regularization of their values, and with use of a unique
      temperature scale, the experimental data of each of these parameters will be
      displayed along the lines of corresponding states that are not restricted to the
      neighborhoods of the nematic-isotropic phase transition point, as it would be the
      case in a usual corresponding states law, but encompass the entire nematic phase.

PMID- 16906888
TI  - Comment on "Solving the riddle of the bright mismatches: labeling and effective
      binding in oligonucleotide arrays".
AB  - In a recent paper [Phys. Rev. E 68, 011906 (2003)], Naef and Magnasco suggested
      that the "bright" mismatches observed in Affymetrix microarray experiments are
      caused by the fluorescent molecules used to label RNA target sequences, which
      would impede target-probe hybridization. Their conclusion is based on the
      observation of "unexpected" asymmetries in the affinities obtained by fitting
      microarray data from publicly available experiments. We point out here that the
      observed asymmetry is due to the inequivalence of RNA and DNA, and that the
      reported affinities are consistent with stacking free energies obtained from
      melting experiments of unlabeled nucleic acids in solution. The conclusion of
      Naef and Magnasco is therefore based on an unjustified assumption.

PMID- 16906890
TI  - Competitive cluster growth in complex networks.
AB  - In this work we propose an idealized model for competitive cluster growth in
      complex networks. Each cluster can be thought of as a fraction of a community
      that shares some common opinion. Our results show that the cluster size
      distribution depends on the particular choice for the topology of the network of
      contacts among the agents. As an application, we show that the cluster size
      distributions obtained when the growth process is performed on hierarchical
      networks, e.g., the Apollonian network, have a scaling form similar to what has
      been observed for the distribution of a number of votes in an electoral process.
      We suggest that this similarity may be due to the fact that social networks
      involved in the electoral process may also possess an underlining hierarchical
      structure.

PMID- 16906891
TI  - Loop calculus in statistical physics and information science.
AB  - Considering a discrete and finite statistical model of a general position we
      introduce an exact expression for the partition function in terms of a finite
      series. The leading term in the series is the Bethe-Peierls (belief propagation)
      (BP) contribution; the rest are expressed as loop contributions on the factor
      graph and calculated directly using the BP solution. The series unveils a small
      parameter that often makes the BP approximation so successful. Applications of
      the loop calculus in statistical physics and information science are discussed.

PMID- 16906892
TI  - Return-volatility correlation in financial dynamics.
AB  - We investigate the return-volatility correlation both local and nonlocal in time
      with daily and minutely data of the German DAX and Chinese indices, and observe a
      leverage effect for the German DAX, while an antileverage effect for the Chinese
      indices. In the negative time direction, i.e., for the volatility-return
      correlation, an antileverage effect nonlocal in time is detected for both the
      German DAX and Chinese indices, although the duplicate local in time does not
      exist. A retarded volatility model may describe the asymmetric properties of the
      financial indices in the positive time direction.

PMID- 16906893
TI  - Large-scale simulations of the two-dimensional melting of hard disks.
AB  - Large-scale computer simulations with more than four million particles have been
      performed to study the melting transition in a two-dimensional hard disk fluid.
      The van der Waals loop previously observed in the pressure-density relationship
      of smaller simulations is shown to disappear systematically with increase in
      sample size, but even with these large system sizes, the freezing transition
      still exhibits what appears to be weakly first-order behavior, though the scaling
      of the bond orientation order is consistent with the Halperin-Nelson-Young
      picture. Above this freezing transition region, scaling analysis of the
      translational order yields a lower bound for the melting density that is much
      higher than previously thought and provides compelling evidence that the solid
      phase first melts into a hexatic phase via a continuous transition, before it
      goes into the isotropic phase.

PMID- 16906894
TI  - Self-similar roughening of drying wet paper.
AB  - We studied the kinetic roughening dynamics of drying wet paper. The
      configurations of dry paper sheets are found to be self-similar, rater than self
      affine. Accordingly, the paper roughening dynamics corresponds to the new class
      of anomalous kinetic roughening [J. J. Ramasco, J. M. Lopez, and M. A. Rodriguez,
      Phys. Rev. Lett. 84, 2199 (2000)], characterized by the equal local and global
      roughness exponents zeta = alpha = 1 and the dynamic exponent z = 1.0+/-0.2,
      whereas the spectral roughness exponent alpha(s) > 1 is determined by the long
      range correlations characterized by the fractal dimension of D crumpled sheet.

PMID- 16906895
TI  - Synchronization is optimal in nondiagonalizable networks.
AB  - We consider maximization of the synchronizability of oscillator networks by
      assigning weights and directions to the links of a given interaction topology. By
      extending the master stability formalism to all possible network structures, we
      show that, unless some oscillator is linked to all the others, maximally
      synchronizable networks are necessarily nondiagonalizable and can always be
      obtained by imposing unidirectional information flow with normalized input
      strengths. The results provide insights into hierarchical structures observed in
      complex networks in which synchronization is important.

PMID- 16906896
TI  - Hidden heat transfer in equilibrium states implies directed motion in
      nonequilibrium states.
AB  - We study a class of heat engines including Feynman's ratchet, which exhibits a
      directed motion of a particle in nonequilibrium steady states maintained by two
      heat baths. We measure heat transfer from each heat bath separately, and average
      them using a careful procedure that reveals the nature of the heat transfer
      associated with directed steps of the particle. Remarkably we find that steps are
      associated with nonvanishing heat transfer even in equilibrium, and there is a
      quantitative relation between this hidden heat transfer and the directed motion
      of the particle. This relation is clearly understood in terms of the principle of
      heat transfer enhancement, which is expected to apply to a large class of highly
      nonequilibrium systems.

PMID- 16906897
TI  - Spurious detection of phase synchronization in coupled nonlinear oscillators.
AB  - Coupled nonlinear systems under certain conditions exhibit phase synchronization,
      which may change for different frequency bands or with the presence of additive
      system noise. In both cases, Fourier filtering is traditionally used to
      preprocess data. We investigate to what extent the phase synchronization of two
      coupled Rossler oscillators depends on (1) the broadness of their power spectrum,
      (2) the width of the bandpass filter, and (3) the level of added noise. We find
      that for identical coupling strengths, oscillators with broader power spectra
      exhibit weaker synchronization. Further, we find that within a broad bandwidth
      range, bandpass filtering reduces the effect of noise but can lead to a spurious
      increase in the degree of phase synchronization with narrowing bandwidth, even
      when the coupling between the two oscillators remains the same.

PMID- 16906898
TI  - Foaming dynamics in Hele-Shaw cells.
AB  - We have studied foaming dynamics in Hele-Shaw cells partially filled with a soap
      and water mixture. A series of upside-down flips produces an intermittent wetting
      of the cell and leads to foam formation. As a function of the number of flips, an
      increasing number of bubbles composes the foam, until saturation is observed.
      Statistical analysis shows that the bubble size follows a Gamma distribution.
      Contrary to common belief, this foaming dynamics by "shaking" creates homogeneous
      foam, even though the system may pass through transient heterogeneous
      configurations. A mechanistic interpretation is proposed and included into a
      theoretical model.

PMID- 16906899
TI  - Self-similar relaxation dynamics of a fluid wedge in a Hele-Shaw cell.
AB  - Let the interface between two immiscible fluids in a Hele-Shaw cell have, at t =
      0, a wedge shape. As a wedge is scale-free, the fluid relaxation dynamics are
      self-similar. We find the dynamic exponent of this self-similar flow and show
      that the interface shape is given by the solution of an unusual inverse problem
      of potential theory. We solve this problem analytically for an almost flat wedge,
      and numerically otherwise. The wedge solution is useful for analysis of pinch-off
      singularities.

PMID- 16906900
TI  - Nonshielded multipolar vortices at high Reynolds number.
AB  - Vortex multipoles--consisting of a core of vorticity closely surrounded by
      several smaller vorticity concentrations of opposite sign--are obtained from the
      evolution of vorticity in two-dimensional simulations. Using a meshless vortex
      method, we obtained triangular and square vortices, surrounded by three and four
      satellites, respectively. These structures have only been observed before to
      emerge from zero-circulation initial conditions. We also observed a pentagon
      vortex. Here, we obtain compound vortices of nonzero total circulation, and
      suggest a gamut of multipolar asymptotic solutions to the Navier-Stokes
      equations.

PMID- 16906901
TI  - Effective front propagation in steady cellular flows: A least time criterion.
AB  - We experimentally study the propagation of a reaction front in a chain of counter
      rotating vortices. The front is induced by an autocatalytic chemical reaction in
      an aqueous solution stirred by electroconvective means. The front propagates by
      getting quickly engulfed in a vortex and by slowly crossing the separatrix to the
      next vortex. Its mean velocity along the chain increases with the flow intensity
      but shows both a bending and a dependence on the vortex aspect ratio. We recover
      these features within a kinematic model of front propagation by seeking the
      quickest front path through a vortex.

PMID- 16906902
TI  - Numerical convergence of the branching time of negative streamers.
AB  - Discharge streamers in experiments branch frequently. Arrayas [Phys. Rev. Lett.
      88, 174502 (2002)] presented simulations of branching streamers and interpreted
      them as physical branching events. The numerical results were criticized by
      Kulikovsky [Phys. Rev. Lett. 89, 229401 (2002)]. Using an adaptive grid
      algorithm, we here present numerical experiments on the effect of grid resolution
      on streamer branching. The convergence of branching time with stepwise finer grid
      sizes provides a quantitative correction on the earlier, low-resolution results
      in overvolted gaps. Furthermore, streamers can branch even in undervolted, but
      sufficiently long gaps, but fewer branching modes are accessible than in higher
      fields.

PMID- 16906903
TI  - Applications of noise theory to plasma fluctuations.
AB  - Noise theory is used to study the temporal correlations of stationary random
      fluctuations that are homogeneous in space. Statistical properties of the
      fluctuations, such as the power spectrum and the correlation function, are
      computed. The results are compared with the observed plasma density fluctuations
      from tokamak experiments.

PMID- 16906904
TI  - Evidence for complete surface wave band gap in a piezoelectric phononic crystal.
AB  - A complete surface acoustic wave band gap is found experimentally in a two
      dimensional square-lattice piezoelectric phononic crystal etched in lithium
      niobate. Propagation in the phononic crystal is studied by direct generation and
      detection of surface waves using interdigital transducers. The complete band gap
      extends from 203 to 226 MHZ, in good agreement with theoretical predictions. Near
      the upper edge of the complete band gap, it is observed that radiation to the
      bulk of the substrate dominates. This observation is explained by introducing the
      concept of the sound line.

PMID- 16906906
TI  - Subdiffractive band-edge solitons in Bose-Einstein condensates in periodic
      potentials.
AB  - A type of matter wave diffraction management is presented that leads to
      subdiffractive solitonlike structures. The proposed management technique uses two
      counter-moving, identical periodic potentials (e.g., optical lattices). For
      suitable lattice parameters, a different type of atomic bandgap structure appears
      in which the effective atomic mass becomes infinite at the lowest edge of an
      energy band. This way, normal matter-wave diffraction (proportional to the square
      of the atomic momentum) is replaced by fourth-order diffraction, and hence the
      evolution of the system becomes subdiffractive.

PMID- 16906905
TI  - Reduced transport velocity of multiply scattered light due to resonant
      scattering.
AB  - The transport properties of photons traveling through random media are of great
      fundamental and applied importance. For instance the dwell time due to resonant
      Mie scattering can lead to a significant reduction in transport velocity. Here,
      we have measured directly the energy-transport velocity of photons in strongly
      scattering media using a combination of time resolved transmission, measuring the
      diffusion coefficient, and angular resolved backscattering, yielding the
      transport mean free path. We find that the transport velocity is strongly reduced
      when the effective diameter of the scattering particles is a multiple of half the
      wavelength. This is consistent with the occurrence of resonant Mie scattering in
      the samples. We compare our data to previous theoretical calculations of the
      transport velocity as a function of scatterer size.

PMID- 16906907
TI  - Solitary and compactlike shear waves in the bulk of solids.
AB  - We show that a model proposed by Rubin, Rosenau, and Gottlieb [J. Appl. Phys. 77,
      4054 (1995)] for dispersion caused by an inherent material characteristic length
      belongs to the class of simple materials. Therefore, it is possible to generalize
      the idea of Rubin, Rosenau, and Gottlieb to include a wide range of material
      models, from nonlinear elasticity to turbulence. Using this insight, we are able
      to fine-tune nonlinear and dispersive effects in the theory of nonlinear
      elasticity in order to generate pulse solitary waves and also bulk traveling
      waves with compact support.

PMID- 16906908
TI  - Failure process of a bundle of plastic fibers.
AB  - We present an extension of fiber bundle models considering that failed fibers
      still carry a fraction 0 < or = alpha < or = 1 of their failure load. The value
      of alpha interpolates between the perfectly brittle failure (alpha = 0) and
      perfectly plastic behavior (alpha = 1) of fibers. We show that the finite load
      bearing capacity of broken fibers has a substantial effect on the failure process
      of the bundle. In the case of global load sharing it is found that for alpha -->
      1 the macroscopic response of the bundle becomes perfectly plastic with a yield
      stress equal to the average fiber strength. On the microlevel, the size
      distribution of avalanches has a crossover from a power law of exponent
      approximately 2.5 to a faster exponential decay. For localized load sharing,
      computer simulations revealed a sharp transition at a well-defined value alpha(c)
      from a phase where macroscopic failure occurs due to localization as a
      consequence of local stress enhancements, to another one where the disordered
      fiber strength dominates the damage process. Analyzing the microstructure of
      damage, the transition proved to be analogous to percolation. At the critical
      point alpha(c), the spanning cluster of damage is found to be compact with a
      fractal boundary. The distribution of bursts of fiber breakings shows a power-law
      behavior with a universal exponent approximately 1.5 equal to the mean-field
      exponent of fiber bundles of critical strength distributions. The model can be
      relevant to understand the shear failure of glued interfaces where failed regions
      can still transmit load by remaining in contact.

PMID- 16906909
TI  - Statistical self-similar properties of complex networks.
AB  - It has been shown that many complex networks shared distinctive features, which
      differ in many ways from the random and the regular networks. Although these
      features capture important characteristics of complex networks, their
      applicability depends on the type of networks. To unravel ubiquitous
      characteristics that complex networks may have in common, we adopt the clustering
      coefficient as the probability measure, and present a systematic analysis of
      various types of complex networks from the perspective of statistical self
      similarity. We find that the probability distribution of the clustering
      coefficient is best characterized by the multifractal; moreover, the support of
      the measure had a fractal dimension. These two features enable us to describe
      complex networks in a unified way; at the same time, offer unforeseen
      possibilities to comprehend complex networks.

PMID- 16906910
TI  - Virial theorem and dynamical evolution of self-gravitating Brownian particles in
      an unbounded domain. I. Overdamped models.
AB  - We derive the virial theorem appropriate to the generalized Smoluchowski-Poisson
      (GSP) system describing self-gravitating Brownian particles in an overdamped
      limit. We extend previous works by considering the case of an unbounded domain
      and an arbitrary equation of state. We use the virial theorem to study the
      diffusion (evaporation) of an isothermal Brownian gas above the critical
      temperature Tc in dimension d = 2 and show how the effective diffusion
      coefficient and the Einstein relation are modified by self-gravity. We also study
      the collapse at T = Tc and show that the central density increases
      logarithmically with time instead of exponentially in a bounded domain. Finally,
      for d > 2, we show that the evaporation of the system is essentially a pure
      diffusion slightly slowed down by self-gravity. We also study the linear
      dynamical stability of stationary solutions of the GSP system representing
      isolated clusters of particles and investigate the influence of the equation of
      state and of the dimension of space on the dynamical stability of the system.

PMID- 16906911
TI  - Virial theorem and dynamical evolution of self-gravitating Brownian particles in
      an unbounded domain. II. Inertial models.
AB  - We propose a general kinetic and hydrodynamic description of self-gravitating
      Brownian particles in d dimensions. We go beyond the usual approximations by
      considering inertial effects and finite-N effects while previous works use a mean
      field approximation valid in a proper thermodynamic limit (N --> +infinity) and
      consider an overdamped regime (xi --> +infinity). We recover known models in some
      particular cases of our general description. We derive the expression of the
      virial theorem for self-gravitating Brownian particles and study the linear
      dynamical stability of isolated clusters of particles and uniform systems by
      using techniques introduced in astrophysics. We investigate the influence of the
      equation of state, of the dimension of space, and of the friction coefficient on
      the dynamical stability of the system. We obtain the exact expression of the
      critical temperature Tc for a multicomponents self-gravitating Brownian gas in d
      = 2. We also consider the limit of weak frictions, xi --> 0, and derive the orbit
      averaged Kramers equation.

PMID- 16906912
TI  - Decoherence, tunneling, and noise-induced activation in a double-potential well
      at high and zero temperature.
AB  - We study the effects of the environment on tunneling in an open system described
      by a static double-well potential. We describe the evolution of a quantum state
      localized in one of the minima of the potential at t = 0, in both the limits of
      high and zero environment temperature. We show that the evolution of the system
      can be summarized in terms of three main physical phenomena--namely, decoherence,
      quantum tunneling, and noise-induced activation--and we obtain analytical
      estimates for the corresponding time scales. These analytical predictions are
      confirmed by large-scale numerical simulations, providing a detailed picture of
      the main stages of the evolution and of the relevant dynamical processes.

PMID- 16906913
TI  - Computer simulations of two-dimensional melting with dipole-dipole interactions.
AB  - We perform molecular dynamics and Monte Carlo simulations of two-dimensional
      melting with dipole-dipole interactions. Both static and dynamic behaviors are
      examined. In the isotropic liquid phase, the bond orientational correlation
      length xi 6 and susceptibility chi 6 are measured, and the data are fitted to the
      theoretical ansatz. An algebraic decay is detected for both spatial and temporal
      bond orientational correlation functions in an intermediate temperature regime,
      and it provides an explicit evidence for the existence of the hexatic phase. From
      the finite-size scaling analysis of the global bond orientational order
      parameter, the disclination unbinding temperature Ti is estimated. In addition,
      from dynamic Monte Carlo simulations of the positional order parameter, we
      extract the critical exponents at the dislocation unbinding temperature Tm. All
      the results are in agreement with those from experiments and support the
      Kosterlitz-Thouless-Halperin-Nelson-Young (KTHNY) theory.

PMID- 16906914
TI  - Structural properties of planar graphs of urban street patterns.
AB  - Recent theoretical and empirical studies have focused on the structural
      properties of complex relational networks in social, biological, and
      technological systems. Here we study the basic properties of twenty 1-square-mile
      samples of street patterns of different world cities. Samples are turned into
      spatial valued graphs. In such graphs, the nodes are embedded in the two
      dimensional plane and represent street intersections, the edges represent
      streets, and the edge values are equal to the street lengths. We evaluate the
      local properties of the graphs by measuring the meshedness coefficient and
      counting short cycles (of three, four, and five edges), and the global properties
      by measuring global efficiency and cost. We also consider, as extreme cases,
      minimal spanning trees (MST) and greedy triangulations (GT) induced by the same
      spatial distribution of nodes. The measures found in the real and the artificial
      networks are then compared. Surprisingly, cities of the same class, e.g., grid
      iron or medieval, exhibit roughly similar properties. The correlation between a
      priori known classes and statistical properties is illustrated in a plot of
      relative efficiency vs cost.

PMID- 16906915
TI  - Synchronized flow and wide moving jams from balanced vehicular traffic.
AB  - Recently we proposed an extension to the traffic model of Aw, Rascle, and
      Greenberg. The extended traffic model can be written as a hyperbolic system of
      balance laws and numerically reproduces the reverse-lambda shape of the
      fundamental diagram of traffic flow. In the current work we analyze the steady
      state solutions of the model and their stability properties. In addition to the
      equilibrium flow curve the trivial steady-state solutions form two additional
      branches in the flow-density diagram. We show that the characteristic structure
      excludes parts of these branches, resulting in the reverse-lambda shape of the
      flow-density relation. The upper branch is metastable against the formation of
      synchronized flow for intermediate densities and unstable for high densities,
      whereas the lower branch is unstable for intermediate densities and metastable
      for high densities. Moreover, the model can reproduce the typical speed of the
      downstream front of wide moving jams. It further reproduces a constant outflow
      from wide moving jams, which is far below the maximum free flow. Applying the
      model to simulate traffic flow at a bottleneck we observe a general pattern with
      wide moving jams traveling through the bottleneck.

PMID- 16906916
TI  - Complex noise in diffusion-limited reactions of replicating and competing
      species.
AB  - We derive exact Langevin-type equations governing quasispecies dynamics. The
      inherent multiplicative noise has both real and imaginary parts. The numerical
      simulation of the underlying complex stochastic partial differential equations is
      carried out employing the Cholesky decomposition for the noise covariance matrix.
      This noise produces unavoidable spatiotemporal density fluctuations about the
      mean-field value. In two dimensions, the fluctuations are suppressed only when
      the diffusion time scale is much smaller than the amplification time scale for
      the master species.

PMID- 16906917
TI  - Universality class of the critical point in the restricted primitive model of
      ionic systems.
AB  - A coarse-grained description of the restricted primitive model is considered in
      terms of the local charge- and number-density fields. Exact reduction to a one
      field theory is derived, and exact expressions for the number-density correlation
      functions in terms of higher-order correlation functions for the charge-density
      are given. It is shown that in continuum space the singularity of the charge
      density correlation function associated with short-wavelength charge-ordering
      disappears when charge-density fluctuations are included by following the
      Brazovskii approach. The related singularity of the individual Feynman diagrams
      contributing to the number-density correlation functions is cured when all the
      diagrams are segregated into disjoint sets according to their topological
      structure. By performing a resummation of all diagrams belonging to each set a
      regular expression represented by a secondary diagram is obtained. The secondary
      diagrams are again segregated into disjoint sets, and the series of all the
      secondary diagrams belonging to a given set is represented by a hyperdiagram. A
      one-to-one correspondence between the hyperdiagrams contributing to the number
      density vertex functions, and diagrams contributing to the order-parameter vertex
      functions in a certain model system belonging to the Ising universality class is
      demonstrated. Corrections to scaling associated with irrelevant operators that
      are present in the model-system Hamiltonian, and other corrections specific to
      the RPM are also discussed.

PMID- 16906918
TI  - Evolving mortal networks.
AB  - We discuss a class of models for the evolution of tree networks in which new
      nodes are recruited into the network at random times, and nodes already in the
      network may die at random times. Stochastic mechanisms for growth and death of
      the network that are either sensitive or insensitive to the coordination number
      or degree of nodes are studied using simulations and mean-field approximations.
      Critical behavior is observed in the long-time coordination number distribution
      of the system; associated exponents are universal in one part of parameter space,
      but depend on the ratio of birth and death parameters elsewhere.

PMID- 16906919
TI  - Derivation of the percolation threshold for the network model of Barabasi and
      Albert.
AB  - The percolation threshold of the network model by Barabasi and Albert [Science
      286, 509 (1999)] (BA) has thus far only been "guessed" based on simulations and
      comparison with other models. Due to the still uncertain influence of
      correlations, the reference to other models cannot be justified. In this paper,
      we explicitly derive the well-known values for the BA model. To underline the
      importance of a null model like that of Barabasi and Albert, we close with two
      basic remarks. First, we establish a connection between the abundance of scale
      free networks in nature and the fact that power-law tails in the degree
      distribution result only from (at least asymptotically) linear preferential
      attachment: Only in the case of linear preferential attachment does a minimum of
      topological knowledge about the network suffice for the attachment process.
      Second, we propose a very simple and realistic extension of the BA model that
      accounts for clustering. We discuss the influence of clustering on the
      percolation properties.

PMID- 16906920
TI  - Geographical effects on the path length and the robustness in complex networks.
AB  - The short paths between any two nodes and the robustness of connectivity are
      advanced properties of scale-free (SF) networks; however, they may be affected by
      geographical constraints in realistic situations. We consider geographical
      networks with the SF structure based on planar triangulation for online routings,
      and suggest scaling relations between the average distance or number of hops on
      the optimal paths and the network size. We also show that the tolerance to random
      failures and attacks on hubs is weakened in geographical networks, and that even
      then it is possible for the extremely vulnerable ones to be improved by adding
      with the local exchange of links.

PMID- 16906921
TI  - Extreme values and fat tails of multifractal fluctuations.
AB  - In this paper we discuss the problem of the estimation of extreme event
      occurrence probability for data drawn from some multifractal process. We also
      study the heavy (power-law) tail behavior of probability density function
      associated with such data. We show that because of strong correlations, the
      standard extreme value approach is not valid and classical tail exponent
      estimators should be interpreted cautiously. Extreme statistics associated with
      multifractal random processes turn out to be characterized by non-self-averaging
      properties. Our considerations rely upon some analogy between random
      multiplicative cascades and the physics of disordered systems and also on recent
      mathematical results about the so-called multifractal formalism. Applied to
      financial time series, our findings allow us to propose an unified framework that
      accounts for the observed multiscaling properties of return fluctuations, the
      volatility clustering phenomenon and the observed "inverse cubic law" of the
      return pdf tails.

PMID- 16906922
TI  - Synchronization landscapes in small-world-connected computer networks.
AB  - Motivated by a synchronization problem in distributed computing we studied a
      simple growth model on regular and small-world networks, embedded in one and two
      dimensions. We find that the synchronization landscape (corresponding to the
      progress of the individual processors) exhibits Kardar-Parisi-Zhang-like kinetic
      roughening on regular networks with short-range communication links. Although the
      processors, on average, progress at a nonzero rate, their spread (the width of
      the synchronization landscape) diverges with the number of nodes (desynchronized
      state) hindering efficient data management. When random communication links are
      added on top of the one and two-dimensional regular networks (resulting in a
      small-world network), large fluctuations in the synchronization landscape are
      suppressed and the width approaches a finite value in the large system-size limit
      (synchronized state). In the resulting synchronization scheme, the processors
      make close-to-uniform progress with a nonzero rate without global intervention.
      We obtain our results by "simulating the simulations," based on the exact
      algorithmic rules, supported by coarse-grained arguments.

PMID- 16906923
TI  - Finite-size scaling of energylike quantities in percolation.
AB  - We study the bond-percolation model in two and three dimensions by Monte Carlo
      simulation, and investigate the finite-size scaling behavior of several
      quantities that account for fluctuations of the total numbers of clusters and
      occupied bonds, Nc and Nb, respectively. These quantities include C(2c) =
      (<N(2)c> - <Nc>2)/Ld and C(cb) = (<NcNb> - <Nc><Nb>)/Ld, where L is the linear
      system size and d is the spatial dimensionality. In statistical models with
      thermal fluctuations, C(2c) and C(cb) are specific heatlike quantities. Despite
      the absence of thermal fluctuations in percolation, we find that the leading
      finite-size scaling of C(2c) and C(cb) is described by the thermal critical
      exponent y(t)-d. We also measure quantity kappa b = 2<NbS2> / <S2> - <NbS4> /
      <S4> - <Nb> and an analogous quantity kappa c for Nc, where S2 and S4 are
      quantities associated with the second and the fourth moments of cluster sizes,
      respectively. At criticality, we show that kappa b and kappa c diverge as L(y)t
      for L --> infinity. The analysis of the data of kappa b and kappa c yields y(t) =
      1.145(2) for the three-dimensional percolation, in good agreement with existing
      results.

PMID- 16906924
TI  - Efficiency of quantum and classical transport on graphs.
AB  - We propose a measure to quantify the efficiency of classical and quantum
      mechanical transport processes on graphs. The measure only depends on the density
      of states (DOS), which contains all the necessary information about the graph.
      For some given (continuous) DOS, the measure shows a power law behavior, where
      the exponent for the quantum transport is twice the exponent of its classical
      counterpart. For small-world networks, however, the measure shows rather a
      stretched exponential law but still the quantum transport outperforms the
      classical one. Some finite tree graphs have a few highly degenerate eigenvalues,
      such that, on the other hand, on them the classical transport may be more
      efficient than the quantum one.

PMID- 16906925
TI  - Chaotic, staggered, and polarized dynamics in opinion forming: The contrarian
      effect.
AB  - We reconsider the no-tie-breaking two-state Galam contrarian model of opinion
      dynamics for update groups of size 3. While the initial model assumes a constant
      density of contrarians a for both opinions, the density now depends for each
      opinion on its global support. Proportionate contrarians are thus found to indeed
      preserve the main results of the former case. However, restricting the contrarian
      behavior to only the current collective majority makes the dynamics more complex
      with additional features. For a density a < a(c) = 1/9 of one-sided contrarians,
      a chaotic basin is found in the 50-50 region separated from two majority-minority
      point attractors, one on each side. For 1/9 < a less similar to 0.301 only the
      chaotic basin survives. In the range a > 0.301 the chaotic basin disappears and
      the majority starts to alternate between the two opinions with a staggered flow
      toward two point attractors. We then study the effect of both decoupling the
      local update time sequence from the contrarian behavior activation and a
      smoothing of the majority rule. A status quo-driven bias for contrarian
      activation is also considered. Introduction of unsettled agents driven in the
      debate on a contrarian basis is shown only to shrink the chaotic basin. The model
      may shed light on recent apparent contradictory elections with on the one hand
      very close results as in the United States in 2000 and in Germany in 2002 and
      2005, and on the other hand, a huge majority as in France in 2002.

PMID- 16906926
TI  - Explanation of the Gibbs paradox within the framework of quantum thermodynamics.
AB  - The issue of the Gibbs paradox is that when considering mixing of two gases
      within classical thermodynamics, the entropy of mixing appears to be a
      discontinuous function of the difference between the gases: it is finite for
      whatever small difference, but vanishes for identical gases. The resolution
      offered in the literature, with help of quantum mixing entropy, was later shown
      to be unsatisfactory precisely where it sought to resolve the paradox.
      Macroscopic thermodynamics, classical or quantum, is unsuitable for explaining
      the paradox, since it does not deal explicitly with the difference between the
      gases. The proper approach employs quantum thermodynamics, which deals with
      finite quantum systems coupled to a large bath and a macroscopic work source.
      Within quantum thermodynamics, entropy generally loses its dominant place and the
      target of the paradox is naturally shifted to a decrease of the maximally
      available work before and after mixing (mixing ergotropy). In contrast to entropy
      this is an unambiguous quantity. For almost identical gases the mixing ergotropy
      continuously goes to zero, thus resolving the paradox. In this approach the
      concept of "difference between the gases" gets a clear operational meaning
      related to the possibilities of controlling the involved quantum states.
      Difficulties which prevent resolutions of the paradox in its entropic formulation
      do not arise here. The mixing ergotropy has several counterintuitive features. It
      can increase when less precise operations are allowed. In the quantum situation
      (in contrast to the classical one) the mixing ergotropy can also increase when
      decreasing the degree of mixing between the gases or when decreasing their
      distinguishability. These points go against a direct association of physical
      irreversibility with lack of information.

PMID- 16906927
TI  - Verification of generic fidelity recovery in a dynamical system.
AB  - We study the time evolution of fidelity in a dynamical many-body system, namely,
      a kicked Ising model, modified to allow for a time-reversal invariance breaking.
      We find good agreement with the random matrix predictions in the realm of strong
      perturbations. In particular for the time-reversal symmetry breaking case the
      predicted revival at the Heisenberg time is clearly seen.

PMID- 16906928
TI  - Complex behavior in driven unidirectionally coupled overdamped Duffing elements.
AB  - It is well known that overdamped unforced dynamical systems do not oscillate.
      However, well-designed coupling schemes, together with the appropriate choice of
      initial conditions, can induce oscillations (corresponding to transitions between
      the stable steady states of each nonlinear element) when a control parameter
      exceeds a threshold value. In recent publications [A. Bulsara, Phys. Rev. E 70,
      036103 (2004); V. In, ibid. 72, 045104 (2005)], we demonstrated this behavior in
      a specific prototype system, a soft-potential mean-field description of the
      dynamics in a hysteretic "single-domain" ferromagnetic sample. These oscillations
      are now finding utility in the detection of very weak "target" magnetic signals,
      via their effect on the oscillation characteristics--e.g., the frequency and
      asymmetry of the oscillation wave forms. We explore the underlying dynamics of a
      related system, coupled bistable "standard quartic" dynamic elements; the system
      shows similarities to, but also significant differences from, our earlier work.
      dc as well as time-periodic target signals are considered; the latter are shown
      to induce complex oscillatory behavior in different regimes of the parameter
      space. In turn, this behavior can be harnessed to quantify the target signal.

PMID- 16906929
TI  - Multiphase-field approach for multicomponent alloys with extrapolation scheme for
      numerical application.
AB  - A multiphase-field model previously proposed by the authors is reformulated in a
      thermodynamically consistent form and extended to multicomponent systems. The
      phase-field and diffusion equations, derived from a free energy functional, are
      compared to those postulated in the previous model in the limit of a binary
      alloy. The constraint of local quasiequilibrium, which is equivalent to the
      postulate of equal diffusion potentials for coexisting phases, is deduced from a
      variational principle. Solute partitioning and evaluation of the thermodynamic
      driving force for phase transformation are done by numerical minimization of the
      free energy of the multiphase system using the Calphad approach. A local
      extrapolation scheme which enhances the computational efficiency for complex
      numerical simulations of technical alloys is presented. It is shown that this
      extrapolation scheme, used in a "multibinary" approximation, reproduces the
      former model without restriction to dilute solutions.

PMID- 16906930
TI  - Structure and evolution of online social relationships: Heterogeneity in
      unrestricted discussions.
AB  - With the advancement in the information age, people are using electronic media
      more frequently for communications, and social relationships are also
      increasingly resorting to online channels. While extensive studies on traditional
      social networks have been carried out, little has been done on online social
      networks. Here we analyze the structure and evolution of online social
      relationships by examining the temporal records of a bulletin board system (BBS)
      in a university. The BBS dataset comprises of 1908 boards, in which a total of
      7446 students participate. An edge is assigned to each dialogue between two
      students, and it is defined as the appearance of the name of a student in the
      from- and to-field in each message. This yields a weighted network between the
      communicating students with an unambiguous group association of individuals. In
      contrast to a typical community network, where intracommunities
      (intercommunities) are strongly (weakly) tied, the BBS network contains hub
      members who participate in many boards simultaneously but are strongly tied, that
      is, they have a large degree and betweenness centrality and provide communication
      channels between communities. On the other hand, intracommunities are rather
      homogeneously and weakly connected. Such a structure, which has never been
      empirically characterized in the past, might provide a new perspective on the
      social opinion formation in this digital era.

PMID- 16906931
TI  - Lattice Boltzmann simulations of phase separation in chemically reactive binary
      fluids.
AB  - We use a lattice Boltzmann method to study pattern formation in chemically
      reactive binary fluids in the regime where hydrodynamic effects are important.
      The coupled equations solved by the method are a Cahn-Hilliard equation, modified
      by the inclusion of a reactive source term, and the Navier-Stokes equations for
      conservation of mass and momentum. The coupling is twofold, resulting from the
      advection of the order parameter by the velocity field and the effect of fluid
      composition on pressure. We study the evolution of the system following a
      critical quench for a linear and for a quadratic reaction source term. Comparison
      is made between the high and low viscosity regimes to identify the influence of
      hydrodynamic flows. In both cases hydrodynamics is found to influence the
      pathways available for domain growth and the eventual steady states.

PMID- 16906933
TI  - Inverted Berezinskii-Kosterlitz-Thouless singularity and high-temperature
      algebraic order in an Ising model on a scale-free hierarchical-lattice small
      world network.
AB  - We have obtained exact results for the Ising model on a hierarchical lattice
      incorporating three key features characterizing many real-world networks--a scale
      free degree distribution, a high clustering coefficient, and the small-world
      effect. By varying the probability p of long-range bonds, the entire spectrum
      from an unclustered, non-small-world network to a highly clustered, small-world
      system is studied. Using the self-similar structure of the network, we obtain
      analytic expressions for the degree distribution P(k) and clustering coefficient
      C for all p, as well as the average path length l for p = 0 and 1. The
      ferromagnetic Ising model on this network is studied through an exact
      renormalization-group transformation of the quenched bond probability
      distribution, using up to 562,500 renormalized probability bins to represent the
      distribution. For p < 0.494, we find power-law critical behavior of the
      magnetization and susceptibility, with critical exponents continuously varying
      with p, and exponential decay of correlations away from Tc. For p > or = 0.494,
      in fact where the network exhibits small-world character, the critical behavior
      radically changes: We find a highly unusual phase transition, namely an inverted
      Berezinskii-Kosterlitz-Thouless singularity, between a low-temperature phase with
      nonzero magnetization and finite correlation length and a high-temperature phase
      with zero magnetization and infinite correlation length, with power-law decay of
      correlations throughout the phase. Approaching Tc from below, the magnetization
      and the susceptibility, respectively, exhibit the singularities of exp(-C/square
      root of Tc - T) and exp(D/square root of Tc - T), with C and D positive
      constants. With long-range bond strengths decaying with distance, we see a phase
      transition with power-law critical singularities for all p, and evaluate an
      unusually narrow critical region and important corrections to power-law behavior
      that depend on the exponent characterizing the decay of long-range interactions.

PMID- 16906932
TI  - Inhomogeneous sandpile model: Crossover from multifractal scaling to finite-size
      scaling.
AB  - We study an inhomogeneous sandpile model in which two different toppling rules
      are defined. For any site only one rule is applied corresponding to either the
      Bak, Tang, and Wiesenfeld model [P. Bak, C. Tang, and K. Wiesenfeld, Phys. Rev.
      Lett. 59, 381 (1987)] or the Manna two-state sandpile model [S. S. Manna, J.
      Phys. A 24, L363 (1991)]. A parameter c is introduced which describes a density
      of sites which are randomly deployed and where the stochastic Manna rules are
      applied. The results show that the avalanche area exponent tau a, avalanche size
      exponent tau s, and capacity fractal dimension Ds depend on the density c. A
      crossover from multifractal scaling of the Bak, Tang, and Wiesenfeld model (c =
      0) to finite-size scaling was found. The critical density c is found to be in the
      interval 0 < c < 0.01. These results demonstrate that local dynamical rules are
      important and can change the global properties of the model.

PMID- 16906934
TI  - Effect of degree correlations on the loop structure of scale-free networks.
AB  - In this paper we study the impact of degree correlations in the subgraph
      statistics of scale-free networks. In particular we consider loops, simple cases
      of network subgraphs which encode the redundancy of the paths passing through
      every two nodes of the network. We provide an understanding of the scaling of the
      clustering coefficient in modular networks in terms of the maximal eigenvector of
      the average adjacency matrix of the ensemble. Furthermore we show that
      correlations affect in a relevant way the average number of Hamiltonian paths in
      a three-core of real world networks. We prove our results in the two-vertex
      correlated hidden variable ensemble and we check the results with exact counting
      of small loops in real graphs.

PMID- 16906935
TI  - Understanding volatility correlation behavior with a magnitude cross-correlation
      function.
AB  - We propose an approach for analyzing the basic relation between correlation
      properties of the original signal and its magnitude fluctuations by decomposing
      the original signal into its positive and negative fluctuation components. We use
      this relation to understand the following phenomenon found in many naturally
      occurring time series: the magnitude of the signal exhibits long-range
      correlation, whereas the original signal is short-range correlated. The
      applications of our approach to heart rate variability signals and high-frequency
      foreign exchange rates reveal that the difference between the correlation
      properties of the original signal and its magnitude fluctuations is induced by
      the time organization structure of the correlation function between the magnitude
      fluctuations of positive and negative components. We show that this correlation
      function can be described well by a stretched-exponential function and is related
      to the nonlinearity and the multifractal structure of the signals.

PMID- 16906936
TI  - Surface critical behavior in Ising magnets: Exact results.
AB  - An exact derivation of the surface magnetizations of the two phases m(1)I and
      m(1)II coexisting below the bulk critical temperature for the semi-infinite two
      dimensional Ising ferromagnet subject to a surface field is given. The surface
      critical behavior of the difference m(1)I - m(1)II is that of the ordinary
      transition only in a limit of a weak surface field below the wetting temperature.

PMID- 16906937
TI  - Distance traveled by random walkers before absorption in a random medium.
AB  - We consider the penetration length l of random walkers diffusing in a medium of
      perfect or imperfect absorbers of number density rho. We solve this problem on a
      lattice and in the continuum in all dimensions D, by means of a mean-field
      renormalization group. For a homogeneous system in D > 2, we find that l is
      similar to max(xi,rho(-1/2)), where is the absorber density correlation length.
      The cases of D = 1 and D = 2 are also treated. In the presence of long-range
      correlations, we estimate the temporal decay of the density of random walkers not
      yet absorbed. These results are illustrated by exactly solvable toy models, and
      extensive numerical simulations on directed percolation, where the absorbers are
      the active sites. Finally, we discuss the implications of our results for
      diffusion limited aggregation (DLA), and we propose a more effective method to
      measure l in DLA clusters.

PMID- 16906938
TI  - Percolation and blind spots in complex networks.
AB  - Recent works on network security have focused on whether a complex network can
      maintain its integrability under attack or random node failures. In applications
      of increasing importance such as sensor networks, a somewhat different problem,
      namely, the occurrence of isolated nodes (or blind spots), is of great interest.
      We show that, for networks with a stronger ability to form global spanning
      clusters, it is relatively more difficult to eliminate blind spots, and vice
      versa. We use the framework of percolation to investigate this phenomenon. Our
      analysis also yields a formula for the average number of blind spots, which
      provide an explanation for several numerical findings.

PMID- 16906939
TI  - Dynamics of information access on the web.
AB  - While current studies on complex networks focus on systems that change relatively
      slowly in time, the structure of the most visited regions of the web is altered
      at the time scale from hours to days. Here we investigate the dynamics of
      visitation of a major news portal, representing the prototype for such a rapidly
      evolving network. The nodes of the network can be classified into stable nodes,
      which form the time-independent skeleton of the portal, and news documents. The
      visitations of the two node classes are markedly different, the skeleton
      acquiring visits at a constant rate, while a news document's visitation peaks
      after a few hours. We find that the visitation pattern of a news document decays
      as a power law, in contrast with the exponential prediction provided by simple
      models of site visitation. This is rooted in the inhomogeneous nature of the
      browsing pattern characterizing individual users: the time interval between
      consecutive visits by the same user to the site follows a power-law distribution,
      in contrast to the exponential expected for Poisson processes. We show that the
      exponent characterizing the individual user's browsing patterns determines the
      power-law decay in a document's visitation. Finally, our results document the
      fleeting quality of news and events: while fifteen minutes of fame is still an
      exaggeration in the online media, we find that access to most news items
      significantly decays after 36 hours of posting.

PMID- 16906940
TI  - Hydrodynamic Lyapunov modes and strong stochasticity threshold in Fermi-Pasta
      Ulam models.
AB  - The existence of a strong stochasticity threshold (SST) has been detected in many
      Hamiltonian lattice systems, including the Fermi-Pasta-Ulam (FPU) model, which is
      characterized by a crossover of the system dynamics from weak to strong chaos
      with increasing energy density epsilon. Correspondingly, the relaxation time to
      energy equipartition and the largest Lyapunov exponent exhibit different scaling
      behavior in the regimes below and beyond the threshold value. In this paper, we
      attempt to go one step further in this direction to explore further changes in
      the energy density dependence of other Lyapunov exponents and of hydrodynamic
      Lyapunov modes (HLMs). In particular, we find that for the FPU-beta and FPU
      alpha(beta) models the scalings of the energy density dependence of all Lyapunov
      exponents experience a similar change at the SST as that of the largest Lyapunov
      exponent. In addition, the threshold values of the crossover of all Lyapunov
      exponents are nearly identical. These facts lend support to the point of view
      that the crossover in the system dynamics at the SST manifests a global change in
      the geometric structure of phase space. They also partially answer the question
      of why the simple assumption that the ambient manifold representing the system
      dynamics is quasi-isotropic works quite well in the analytical calculation of the
      largest Lyapunov exponent. Furthermore, the FPU-beta model is used as an example
      to show that HLMs exist in Hamiltonian lattice models with continuous symmetries.
      Some measures are defined to indicate the significance of HLMs. Numerical
      simulations demonstrate that there is a smooth transition in the energy density
      dependence of these variables corresponding to the crossover in Lyapunov
      exponents at the SST. In particular, our numerical results indicate that strong
      chaos is essential for the appearance of HLMs and those modes become more
      significant with increasing degree of chaoticity.

PMID- 16906941
TI  - Theory of 2 delta-kicked quantum rotors.
AB  - We examine the quantum dynamics of cold atoms subjected to pairs of closely
      spaced delta kicks from standing waves of light and find behavior quite unlike
      the well-studied quantum kicked rotor (QKR). We show that the quantum phase space
      has a periodic, cellular structure arising from a unitary matrix with oscillating
      bandwidth. The corresponding eigenstates are exponentially localized, but scale
      with a fractional power L is less similar to h(-0.75), in contrast to the QKR for
      which L is less similar to h(-1). The effect of intercell (and intracell)
      transport is investigated by studying the spectral fluctuations with both
      periodic as well as "open" boundary conditions.

PMID- 16906942
TI  - Nonstationary Pomeau-Manneville intermittency in systems with a periodic
      parameter change.
AB  - Pomeau-Manneville intermittency in nonstationary systems is investigated. If one
      of the parameters characterizing a dynamical system is changed periodically,
      periodic orbits may appear even when the value of this parameter remains in a
      range which, in the stationary case, yields chaotic behavior. This property may
      be used for the control of systems exhibiting intermittency. If the parameter
      change is not large enough, a periodic orbit does not appear but the distribution
      of the laminar phases is modified. In the case of type I intermittency, this
      means a broadening of such a distribution or, alternatively, a splitting of its
      right peak. We present a theory of these phenomena. Numerical simulations both
      for one-dimensional maps and for flows support our predictions. Some of the
      phenomena discussed here were observed earlier in time series of heart rate
      variability.

PMID- 16906943
TI  - Adaptive-feedback control algorithm.
AB  - This paper is motivated by giving the detailed proofs and some interesting
      remarks on the results the author obtained in a series of papers [Phys. Rev.
      Lett. 93, 214101 (2004); Phys. Rev. E 71, 037203 (2005); 69, 067201 (2004)],
      where an adaptive-feedback algorithm was proposed to effectively stabilize and
      synchronize chaotic systems. This note proves in detail the strictness of this
      algorithm from the viewpoint of mathematics, and gives some interesting remarks
      for its potential applications to chaos control & synchronization. In addition, a
      significant comment on synchronization-based parameter estimation is given, which
      shows some techniques proposed in literature less strict and ineffective in some
      cases.

PMID- 16906944
TI  - Minimal model for spatial coherence resonance.
AB  - We show that a planar medium, locally modeled by a simple one-dimensional
      excitable system with a piece-wise linear potential, can serve as a minimal model
      for spatial coherence resonance. Via an analytical treatment of the spatially
      extended system, we derive the dependence of the resonant wave number on several
      crucial system parameters, ranging from the diffusion coefficient to the local
      excursion time of constitutive excitable units. Thus, we provide vital insights
      into mechanisms that enable the emergence of exclusively noise-induced spatial
      periodicity in excitable media.

PMID- 16906945
TI  - Square superlattice pattern in dielectric barrier discharge.
AB  - We report the observation of a square superlattice pattern in a dielectric
      barrier discharge system. The correlation measurements indicate that the square
      superlattice pattern is an interleaving of two different transient square
      sublattices. The interplay between the charge pattern and the discharge filament
      pattern is discussed.

PMID- 16906946
TI  - Ring-shaped luminescence pattern in biased quantum wells studied as a steady
      state reaction front.
AB  - Under certain conditions, focused laser excitation in semiconductor quantum well
      structures can lead to a charge separation and a circular reaction front, which
      is visible as a ring-shaped photoluminescence pattern. The diffusion-reaction
      equations governing the system are studied here with the aim of a detailed
      understanding of the steady state. The qualitative asymmetry in the sources for
      the two carriers is found to lead to unusual effects which dramatically affect
      the steady-state configuration. Analytic expressions are derived for carrier
      distributions and interface positions for a number of cases. These are compared
      with steady-state information obtained from simulations of the diffusion-reaction
      equations.

PMID- 16906947
TI  - Ferrofluidic torsional pendulum driven by oscillating magnetic field.
AB  - A thin disk-shaped container filled with a ferrofluid and suspended in a
      horizontal linearly polarized ac magnetic field can perform torsional vibrations
      around its vertical diameter. In contrast to a recently studied spherical
      pendulum, the cell is sensitive to the field direction: It exposes its edge to
      the stationary or slowly oscillating magnetic field, and its broad side to the
      field of a high frequency. When the amplitude of the latter field is increased,
      the state of rest gets destabilized, yielding to oscillations near the
      equilibrium. Further growth of the field strength results in the onset of the
      cell rotation. We describe sequences of local and global bifurcations which
      accompany those transitions.

PMID- 16906948
TI  - Chaotic observer-based synchronization under information constraints.
AB  - Limitations of observer-based synchronization systems under information
      constraints (limited information capacity of the coupling channel) are evaluated.
      We give theoretical analysis for multidimensional drive-response systems
      represented in the Lurie form (linear part plus nonlinearity depending only on
      measurable outputs). It is shown that the upper bound of the limit
      synchronization error (LSE) is proportional to the upper bound of the
      transmission error. As a consequence, the upper and lower bounds of LSE are
      proportional to the maximum rate of the coupling signal and inversely
      proportional to the information transmission rate (channel capacity). Optimality
      of the binary coding for coders with one-step memory is established. The results
      are applied to synchronization of two chaotic Chua systems coupled via a channel
      with limited capacity.

PMID- 16906949
TI  - Clustering in randomly driven Hamiltonian systems.
AB  - The motion of oscillatorylike nonlinear Hamiltonian systems, driven by a weak
      noise, is considered. A general method to find regions of stability in the phase
      space of a randomly driven system, based on a specific Poincare map, is proposed
      and justified. Physical manifestations of these regions of stability are coherent
      clusters. We illustrate the method and demonstrate the appearance of coherent
      clusters with two models motivated by the problems of waveguide sound propagation
      and Lagrangian mixing of passive scalars in the ocean. We find bunches of sound
      rays propagating coherently in an underwater waveguide through a randomly
      fluctuating ocean at long distances. We find clusters of passive particles to be
      advected coherently for a comparatively long time by a random two-dimensional
      flow modeling mixing around a fixed vortex.

PMID- 16906950
TI  - Harmonic versus subharmonic patterns in a spatially forced oscillating chemical
      reaction.
AB  - The effects of a spatially periodic forcing on an oscillating chemical reaction
      as described by the Lengyel-Epstein model are investigated. We find a surprising
      competition between two oscillating patterns, where one is harmonic and the other
      subharmonic with respect to the spatially periodic forcing. The occurrence of a
      subharmonic pattern is remarkable as well as its preference up to rather large
      values of the modulation amplitude. For small modulation amplitudes we derive
      from the model system a generic equation for the envelope of the oscillating
      reaction that includes an additional forcing contribution, compared to the
      amplitude equations known from previous studies in other systems. The analysis of
      this amplitude equation allows the derivation of analytical expressions even for
      the forcing corrections to the threshold and to the oscillation frequency, which
      are in a wide range of parameters in good agreement with the numerical analysis
      of the complete reaction equations. In the nonlinear regime beyond threshold, the
      subharmonic solutions exist in a finite range of the control parameter that has
      been determined by solving the reaction equations numerically for various sets of
      parameters.

PMID- 16906951
TI  - Fidelity freeze for a random matrix model with off-diagonal perturbation.
AB  - The concept of fidelity has been introduced to characterize the stability of a
      quantum-mechanical system against perturbations. The fidelity amplitude is
      defined as the overlap integral of a wave packet with itself after the
      development forth and back under the influence of two slightly different
      Hamiltonians. It was shown by Prosen and Znidaric in the linear-response
      approximation that the decay of the fidelity is frozen if the Hamiltonian of the
      perturbation contains off-diagonal elements only. In the present work the results
      of Prosen and Znidaric are extended by a supersymmetry calculation to arbitrary
      strengths of the perturbation for the case of an unperturbed Hamiltonian taken
      from the Gaussian orthogonal ensemble and a purely imaginary antisymmetric
      perturbation. It is found that for the exact calculation the freeze of fidelity
      is only slightly reduced as compared to the linear-response approximation. This
      may have important consequences for the design of quantum computers.

PMID- 16906952
TI  - Resonant pattern formation in active media driven by time-dependent flows.
AB  - The effect of a time-dependent flow in an oscillatory chemical system supporting
      front propagation is studied. Resonant target patterns depend on the strength and
      frequency of the time-dependent flow. The flow time scale needed to entrain the
      system to the resonant target period of oscillation depends on the closeness to
      the natural oscillation frequency of the medium. The flow strength needed to
      obtain these patterns is interpreted in terms of mixing optimization, and we give
      conditions for the flow that guarantee the best mixing with the Bernoulli
      property.

PMID- 16906953
TI  - Stable isochronal synchronization of mutually coupled chaotic lasers.
AB  - The dynamics of two mutually coupled chaotic diode lasers are investigated
      experimentally and numerically. By adding self-feedback to each laser, stable
      isochronal synchronization is established. This stability, which can be achieved
      for symmetric operation, is essential for constructing an optical public-channel
      cryptographic system. The experimental results on diode lasers are well described
      by rate equations of coupled single mode lasers.

PMID- 16906954
TI  - Incipience of quantum chaos in the Jahn-Teller model.
AB  - We studied complex spectra of a two-level electron system coupled to two phonon
      (vibron) modes represented by the product of E and e Jahn-Teller model. For
      particular rotation quantum numbers we found a coexistence of up to three regions
      of the spectra: (i) the dimerized region of long-range-ordered (extended) pairs
      of oscillating levels, (ii) the short-range-ordered (localized) "kink lattice" of
      avoiding levels, and (iii) the intermediate region of kink nucleation with
      variable range of ordering. This structure appears above a certain critical line
      as a function of interaction strength. The level clustering and level avoiding
      generic patterns reflect themselves in several intermittent regions between up to
      three branches of spectral entropies. Linear scaling behavior of the widths of
      level curvature probability distributions provides the conventionally adopted
      indication for the presence of quantum chaos. Level spacing probability
      distributions show peculiarities of the partial (for fixed quantum angular
      momentum) as well as of the cumulative (all angular momenta) case. The clustering
      of levels with two and three dominant spacings at fixed angular momenta causes
      notable deviations of the cumulative distributions from the Poissonian one.

PMID- 16906955
TI  - Nonlinear parametric model for Granger causality of time series.
AB  - The notion of Granger causality between two time series examines if the
      prediction of one series could be improved by incorporating information of the
      other. In particular, if the prediction error of the first time series is reduced
      by including measurements from the second time series, then the second time
      series is said to have a causal influence on the first one. We propose a radial
      basis function approach to nonlinear Granger causality. The proposed model is not
      constrained to be additive in variables from the two time series and can
      approximate any function of these variables, still being suitable to evaluate
      causality. Usefulness of this measure of causality is shown in two applications.
      In the first application, a physiological one, we consider time series of heart
      rate and blood pressure in congestive heart failure patients and patients
      affected by sepsis: we find that sepsis patients, unlike congestive heart failure
      patients, show symmetric causal relationships between the two time series. In the
      second application, we consider the feedback loop in a model of excitatory and
      inhibitory neurons: we find that in this system causality measures the combined
      influence of couplings and membrane time constants.

PMID- 16906956
TI  - Measure of orbital stickiness and chaos strength.
AB  - Patterns can be used effectively to characterize dynamical orbits as regular or
      chaotic. The proposed method focuses on local, epochal characterization of orbits
      as opposed to global characterization usually employed by most established
      measures. The "patterns method" provides essentially a measure of chaos strength
      for every extremum of a signal. For this reason, it provides information about
      sticky epochs of chaotic orbits, as well as time-dependent orbits. This way it
      can be used to give extremely detailed pictures of the phase space of a system,
      as well as to provide characterizations early in the evolution of orbits.
      Moreover, the method applies generally; all that is required is a signal, of
      which an orbit is merely an example.

PMID- 16906957
TI  - Propagation failure dynamics of wave trains in excitable systems.
AB  - We report experimental and numerical results on temporal patterns of propagation
      failures in reaction-diffusion systems. Experiments employ the 1,4
      cyclohexanedione Belousov-Zhabotinsky reaction. The propagation failures occur in
      the frontier region of the wave train and can profoundly affect its expansion
      speed. The specific rhythms observed vary from simple periodic to highly complex
      and possibly chaotic sequences. All but the period-1 sequences are found in the
      transition region between "merging" and "tracking" dynamics, which correspond to
      wave behavior caused by two qualitatively different types of anomalous dispersion
      relations.

PMID- 16906958
TI  - Line-defects-mediated complex-oscillatory spiral waves in a chemical system.
AB  - In this paper, we summarize our experimental observations on complex-oscillatory
      spiral waves that arise in a Belousov-Zhabotinsky (BZ) reaction-diffusion system.
      The observed wave structures generically bear line defects across which the phase
      of local oscillation changes by a multiple of 2 pi. The local oscillation at
      every spatial point along a line defect of period-2 (P-2) oscillatory media is
      period-1 (P-1) oscillatory. For the homogeneous BZ reaction can be excitable,
      simply periodic, complex periodic, or chaotic as the control parameters are
      tuned, a number of different complex wave states are revealed. A two-dimensional
      phase diagram, which includes domains of P-2 oscillatory spirals, intermittently
      breathing spirals, period-3 (P-3) oscillatory spirals, two different types of
      mixed-mode periodic spirals, and line-defect-mediated turbulence, is constructed.
      Several different transitions among different dynamic states are described
      systematically. In all cases, line defects are found to play an important role.

PMID- 16906959
TI  - Stimulus-locked responses of two phase oscillators coupled with delayed feedback.
AB  - For a system of two phase oscillators coupled with delayed self-feedback we study
      the impact of pulsatile stimulation administered to both oscillators. This system
      models the dynamics of two coupled phase-locked loops (PLLs) with a finite
      internal delay within each loop. The delayed self-feedback leads to a rich
      variety of dynamical regimes, ranging from phase-locked and periodically
      modulated synchronized states to chaotic phase synchronization and
      desynchronization. Remarkably, for large coupling strength the two PLLs are
      completely desynchronized. We study stimulus-locked responses emerging in the
      different dynamical regimes. Simple phase resets may be followed by a response
      clustering, which is intimately connected with long poststimulus
      resynchronization. Intriguingly, a maximal perturbation (i.e., maximal response
      clustering and maximal resynchronization time) occurs, if the system gets trapped
      at a stable manifold of an unstable saddle fixed point due to appropriately
      calibrated stimulus. Also, single stimuli with suitable parameters can shift the
      system from a stable synchronized state to a stable desynchronized state or vice
      versa. Our result show that appropriately calibrated single pulse stimuli may
      cause pronounced transient and/or long-lasting changes of the oscillators'
      dynamics. Pulse stimulation may, hence, constitute an effective approach for the
      control of coupled oscillators, which might be relevant to both physical and
      medical applications.

PMID- 16906960
TI  - Inhibitory neurons can facilitate rhythmic activity in a neural network.
AB  - Synchrony emerges in a population of oscillators interacting through in-phase
      couplings. We addressed a question of whether inhibitory neurons simply hinder
      the emergence of the synchronous activity among excitatory neurons, or facilitate
      it. An analysis of a simple phase model revealed that both cases may take place.
      Numerical simulations of the more realistic models revealed that inhibitory
      neurons rather facilitate rhythmic activity.

PMID- 16906961
TI  - Spectroscopic properties of large open quantum-chaotic cavities with and without
      separated time scales.
AB  - The spectroscopic properties of an open large Bunimovich cavity are studied
      numerically in the framework of the effective Hamiltonian formalism. The cavity
      is opened by attaching two leads to it in four different ways. In some cases, the
      transmission takes place via standing waves with an intensity that closely
      follows the profile of the resonances. In other cases, short-lived and long-lived
      resonance states coexist. The short-lived states cause traveling waves in the
      transmission while the long-lived ones generate superposed fluctuations. The
      traveling waves oscillate as a function of energy. They are not localized in the
      interior of the large chaotic cavity. In all considered cases, the phase rigidity
      fluctuates with energy. It is mostly near to its maximum value and agrees well
      with the theoretical value for the two-channel case.

PMID- 16906962
TI  - Dissipative area-preserving one-dimensional Fermi accelerator model.
AB  - The influence of dissipation on the simplified Fermi-Ulam accelerator model
      (SFUM) is investigated. The model is described in terms of a two-dimensional
      nonlinear mapping obtained from differential equations. It is shown that a
      dissipative SFUM possesses regions of phase space characterized by the property
      of area preservation.

PMID- 16906963
TI  - Boundary-induced spatiotemporal complex patterns in excitable systems.
AB  - We show that inhomogeneous boundary conditions (BCs) in a distributed reaction
      diffusion excitable system are a natural source of permanent perturbations that
      can induce wave trains, which can be characterized as mixed-mode temporal
      oscillations and, when a parameter is varied, admit a period-adding bifurcation.
      To that end we analyze: a pair of coupled excitable and oscillatory cells, a
      distributed FitzHugh-Nagumo model, and a distributed five-variable model that
      describes catalytic oxidation. The obtained results account for the recently
      reported experimental observations of mixed-mode oscillations showing a period
      adding bifurcation during oxidation on a disk-shaped catalytic cloth with imposed
      cold temperature BC.

PMID- 16906964
TI  - Wave instability induced by nonlocal spatial coupling in a model of the light
      sensitive Belousov-Zhabotinsky reaction.
AB  - We study spatiotemporal patterns resulting from instabilities induced by nonlocal
      spatial coupling in the Oregonator model of the light-sensitive Belousov
      Zhabotinsky reaction. In this system, nonlocal coupling can be externally imposed
      by means of an optical feedback loop which links the intensity of locally applied
      illumination with the activity in a certain vicinity of a particular point
      weighted by a given coupling function. This effect is included in the three
      variable Oregonator model by an additional integral term in the photochemically
      induced bromide flow. A linear stability analysis of this modified Oregonator
      model predicts that wave and Turing instabilities of the homogeneous steady state
      can be induced for experimentally realistic parameter values. In particular, we
      find that a long-range inhibition in the optical feedback leads to a Turing
      instability, while a long-range activation induces wave patterns. Using a weakly
      nonlinear analysis, we derive amplitude equations for the wave instability which
      are valid close to the instability threshold. Therein, we find that the wave
      instability occurs supercritically or subcritically and that traveling waves are
      preferred over standing waves. The results of the theoretical analysis are in
      good agreement with numerical simulations of the model near the wave instability
      threshold. For larger distances from threshold, a secondary breathing instability
      is found for traveling waves.

PMID- 16906965
TI  - Escape of trajectories from a vase-shaped cavity.
AB  - We consider the escape of ballistic trajectories from an open, vase-shaped
      cavity. Such a system serves as a model for microwaves escaping from a cavity or
      electrons escaping from a microjunction. Fixing the initial position of a
      particle and recording its escape time as a function of the initial launch
      direction, the resulting escape-time plot shows "epistrophic fractal" structure-
      repeated structure within structure at all levels of resolution with new features
      appearing in the fractal at longer time scales. By launching trajectories
      simultaneously in all directions (modeling an outgoing wave), a detector placed
      outside the cavity would measure a train of escaping pulses. We connect the
      structure of this chaotic pulse train with the fractal structure of the escape
      time plot.

PMID- 16906966
TI  - Application of the trace formula in pseudointegrable systems.
AB  - We apply periodic-orbit theory to calculate the integrated density of states N(k)
      of the quantum mechanical eigenvalues from the periodic orbits of
      pseudointegrable polygon and barrier billiards. We show that the results agree so
      well with the density of states obtained from numerical solutions of the
      Schrodinger equation that about the first 100 eigenvalues can be obtained
      directly from the periodic-orbit calculations with good accuracy.

PMID- 16906967
TI  - Accuracy and efficiency of reduced stochastic models for chaotic Hamiltonian
      systems with time-scale separation.
AB  - The study of the long time behavior of systems with time-scale separation is
      considerably facilitated if the fast degrees of freedom can be eliminated without
      affecting the slow dynamics. We investigate a technique in which the fluctuations
      due to a fast chaotic subsystem are replaced by a suitable stochastic process so
      that a Fokker-Planck equation for the slow variables results. The accuracy and
      efficiency of this technique is verified by the detailed numerical investigation
      of several coupled systems. The asymptotic behavior as well as transients turn
      out to be well modeled by the reduced dynamics. We concentrate on low-dimensional
      problems and cover different types of coupling schemes as well as different
      chaotic subsystems. As a physical application we discuss the classical dynamics
      of a hydrogen atom in a strong magnetic field.

PMID- 16906968
TI  - Fermi acceleration on the annular billiard.
AB  - We study the phenomenon of unlimited energy growth for a classical particle
      moving in the annular billiard. The model is considered under two different
      geometrical situations: static and breathing boundaries. We show that when the
      dynamics is chaotic for the static case, the introduction of a time-dependent
      perturbation allows that the particle experiences the phenomenon of Fermi
      acceleration even when the oscillations are periodic.

PMID- 16906969
TI  - Variability-induced transition in a net of neural elements: From oscillatory to
      excitable behavior.
AB  - Starting with an oscillatory net of neural elements, increasing variability
      induces a phase transition to excitability. This transition is explained by a
      systematic effect of the variability, which stabilizes the formerly unstable,
      spatially uniform, temporally constant solution of the net. Multiplicative noise
      may also influence the net in a systematic way and may thus induce a similar
      transition. Adding noise into the model, the interplay of noise and variability
      with respect to the reported transition is investigated. Finally, pattern
      formation in a diffusively coupled net is studied, because excitability implies
      the ability of pattern formation and information transmission.

PMID- 16906970
TI  - Hydromagnetic instability in differentially rotating flows.
AB  - We study the stability of compressible differentially rotating flows in the
      presence of the magnetic field, and we show that the compressibility profoundly
      alters the previous results for a magnetized incompressible flow. The necessary
      condition of newly found instability can be easily satisfied in various flows in
      laboratory and astrophysical conditions and reads BsBphiOmega' not equal to 0,
      where Bs and Bphi are the radial and azimuthal components of the magnetic field,
      Omega' = d Omega/ds with s being the cylindrical radius. Contrary to the well
      known magnetorotational instability that occurs only if omega decreases with s,
      the instability considered in this paper may occur at any sign of Omega'. The
      instability can operate even in a very strong magnetic field that entirely
      suppresses the standard magnetorotational instability. The growth time of
      instability can be as short as a few rotation periods.

PMID- 16906971
TI  - Fractal-like tree networks reducing the thermal conductivity.
AB  - The effective thermal conductivity of composites with embedded self-similar H
      shaped fractal-like tree networks is studied. It is found that the effective
      thermal conductivity of the composites with these networks is related to the
      structures of the networks and the ratio of the component thermal conductivities:
      the longer the branches, the lower the thermal conductivity; the smaller the
      ratio (beta) of successive branch diameters, the lower the thermal conductivity;
      the denser the network, the lower the thermal conductivity. It is also found that
      the thermal conductivity of the H-shaped fractal-like tree networks does not obey
      Murray's law. The present results show that a network embedded in a composite
      plays an important role, and the thermal conductivity of the network itself may
      be less than that of the original material by several orders of magnitude.
      Fractal-like tree networks can significantly reduce the thermal conductivity
      compared to an equivalent single cylinder.

PMID- 16906972
TI  - Edge pinch instability of liquid metal sheet in a transverse high-frequency ac
      magnetic field.
AB  - We analyze the linear stability of the edge of a thin liquid metal layer subject
      to a transverse high-frequency ac magnetic field. The layer is treated as a
      perfectly conducting liquid sheet that allows us to solve the problem
      analytically for both a semi-infinite geometry with a straight edge and a thin
      disk of finite radius. It is shown that the long-wave perturbations of a straight
      edge are monotonically unstable when the wave number exceeds the critical value
      k(c) = F0/(gamma l0), which is determined by the linear density of the
      electromagnetic force F0 acting on the edge, the surface tension gamma, and the
      effective arclength of edge thickness l0. Perturbations with wavelength shorter
      than critical are stabilized by the surface tension, whereas the growth rate of
      long-wave perturbations reduces as similar to k for k --> 0. Thus, there is the
      fastest growing perturbation with the wave number k max = 2/3 k(c). When the
      layer is arranged vertically, long-wave perturbations are stabilized by the
      gravity, and the critical perturbation is characterized by the capillary wave
      number k(c) = square root of (g rho/gamma), where g is the acceleration due to
      gravity and rho is the density of metal. In this case, the critical linear
      density of electromagnetic force is F(0,c) = 2k(c)l0 gamma, which corresponds to
      the critical current amplitude I(0,c) = 4 square root of (pi k(c) l0L gamma/mu 0)
      when the magnetic field is generated by a straight wire at the distance L
      directly above the edge. By applying the general approach developed for the semi
      infinite sheet, we find that a circular disk of radius R0 placed in a transverse
      uniform high-frequency ac magnetic field with the induction amplitude B0 becomes
      linearly unstable with respect to exponentially growing perturbation with the
      azimuthal wave number m = 2 when the magnetic Bond number exceeds Bm(c) = B(0)2
      R(0)2 / (2 mu 0 l0 gamma) = 3 pi. For Bm > Bm(c), the wave number of the fastest
      growing perturbation is m(max) = [2Bm/(3 pi)]. These theoretical results agree
      well with the experimental observations.

PMID- 16906973
TI  - Power law of decaying homogeneous isotropic turbulence at low Reynolds number.
AB  - We focus on an estimate of the decay exponent (m) in the initial period of decay
      of homogeneous isotropic turbulence at low Taylor microscale Reynolds number R
      lambda (approximately equal to 20-50). Lattice Boltzmann simulations in a
      periodic box of 256(3) points are performed and compared with measurements in
      grid turbulence at similar R lambda. Good agreement is found between measured and
      calculated energy spectra. The exponent m is estimated in three different ways:
      from the decay of the turbulent kinetic energy, the decay of the mean energy
      dissipation rate, and the rate of growth of the Taylor microscale. Although all
      estimates are close, as prescribed by theory, that from the Taylor microscale has
      the largest variability. It is then suggested that the virtual origin for the
      decay rate be determined from the Taylor microscale, but the actual value of m be
      estimated from the decay rate of the kinetic energy. The dependence of m on R
      lambda(0) (the value of R lambda at the beginning of the simulation) is also
      analyzed, using the present data as well as data from the literature. The results
      confirmed that m approaches 1, as R lambda(0) increases.

PMID- 16906974
TI  - Explosion triggering by an accelerating flame.
AB  - The analytical theory of explosion triggering by an accelerating flame is
      developed. The theory describes the structure of a one-dimensional isentropic
      compression wave pushed by the flame front. The condition of explosion in the gas
      mixture ahead of the flame front is derived; the instant of the explosion is
      determined provided that a mechanism of chemical kinetics is known. As an
      example, it is demonstrated how the problem is solved in the case of a single
      reaction of Arrhenius type, controlling combustion both inside the flame front
      and ahead of the flame. The model of an Arrhenius reaction with a cutoff
      temperature is also considered. The limitations of the theory due to the shock
      formation in the compression wave are found. Comparison of the theoretical
      results to the previous numerical simulations shows good agreement.

PMID- 16906975
TI  - Analysis of the electromeniscus phenomenon using a different interpretation of
      the Maxwell model applied to three-dimensional molecular orientations.
AB  - An electrohydrodynamic phenomenon called the electromeniscus is analyzed. This
      phenomenon is closely related to the oscillation of a microscale liquid and is
      analyzed using an interpretation of the Maxwell model coupled with a variational
      principle. The analysis clearly shows that the electromeniscus phenomenon is
      generated as a result of mass transformation of the oscillating liquid in order
      to transform the electric energy at the electrode to kinetic energy of the liquid
      most efficiently through their resonance. Mass transformation is a characteristic
      phenomenon of a liquid, and control of this phenomenon demonstrates great
      potential for self-aligning nanoscale materials and production of functional
      polymers characterized by specific molecular orientations.

PMID- 16906976
TI  - Stochastic dynamo model for subcritical transition.
AB  - The effects of stochastic perturbations in a nonlinear alpha Omega-dynamo model
      are investigated. By using transformation of variables we identify a "slow"
      variable that determines the global evolution of the non-normal alpha Omega
      dynamo system in the subcritical case. We apply an adiabatic elimination
      procedure to derive a closed stochastic differential equation for the slow
      variable for which the dynamics is determined along one of the eigenvectors of
      the full system. We derive the corresponding Fokker-Planck equation and show that
      the generation of a large scale magnetic field can be regarded as a first-order
      phase transition. We show that the an advantage of the reduced system is that we
      have explicit expressions for both the stochastic and deterministic potentials.
      We also obtain the stationary solution of the Fokker-Planck equation and show
      that an increase in the intensity of the multiplicative noise leads to
      qualitative changes in the stationary probability density function. The latter
      can be interpreted as a noise-induced phase transition. By a numerical simulation
      of the stochastic galactic dynamo model, we show that the qualitative behavior of
      the "empirical" stationary pdf of the slow variable is accurately predicted by
      the stationary pdf of the reduced system.

PMID- 16906977
TI  - Phase field approach to spatial perturbations in normal Saffman-Taylor fingers.
AB  - We make a numerical study of the effect that spatial perturbations have in normal
      Saffman-Taylor fingers driven at constant pressure gradients. We use a phase
      field model that allows for spatial variations in the Hele-Shaw cell. We find
      that, regardless of the specific way in which spatial perturbations are
      introduced, a lateral instability develops on the sides of the propagating
      Saffman-Taylor finger. Moreover, the instability exists regardless of the
      intensity of spatial perturbations in the cell as long as the perturbations are
      felt by the finger tip. If, as the finger propagates, the spatial perturbations
      felt by the tip change, the instability is nonperiodic. If, as the finger
      propagates, the spatial perturbations felt by the tip are persistent, the
      instability developed is periodic. In the later case, the instability is
      symmetrical or asymmetrical depending on the intensity of the perturbation.

PMID- 16906978
TI  - Effect of the centrifugal force on domain chaos in Rayleigh-Benard convection.
AB  - Experiments and simulations from a variety of sample sizes indicated that the
      centrifugal force significantly affects the domain-chaos state observed in
      rotating Rayleigh-Benard convection-patterns. In a large-aspect-ratio sample, we
      observed a hybrid state consisting of domain chaos close to the sample center,
      surrounded by an annulus of nearly stationary nearly radial rolls populated by
      occasional defects reminiscent of undulation chaos. Although the Coriolis force
      is responsible for domain chaos, by comparing experiment and simulation we show
      that the centrifugal force is responsible for the radial rolls. Furthermore,
      simulations of the Boussinesq equations for smaller aspect ratios neglecting the
      centrifugal force yielded a domain precession-frequency f approximately
      epsilon(mu) with mu approximately equal to 1 as predicted by the amplitude
      equation model for domain chaos, but contradicted by previous experiment.
      Additionally the simulations gave a domain size that was larger than in the
      experiment. When the centrifugal force was included in the simulation, mu and the
      domain size were consistent with experiment.

PMID- 16906979
TI  - Nonlinear Marangoni convection with the inclined temperature gradient in
      multilayer systems.
AB  - The influence of the horizontal component of the temperature gradient on
      nonlinear regimes of oscillatory Marangoni convection in a real symmetric three
      layer system is investigated. The transitions between different flow regimes have
      been studied. The general diagram of regimes is constructed.

PMID- 16906980
TI  - Nonradiative surface plasmon assisted microscale Marangoni forces.
AB  - When a liquid droplet experiences a temperature inhomogeneity along its bounding
      surface, a surface energy gradient is engendered, which when, in a continuous
      sense, exceeding a threshold, results in a convective flow dissipating the
      energy. If the associated temperature gradients are sustained by the interface
      between the liquid and a supporting substrate, the induced flow can result in the
      lateral motion of the droplet overcoming the viscosity and inertia. Recently,
      pico-liter adsorbed and applied droplets were shown experimentally to be
      transported, and divided by the decay of optically excited surface plasmons into
      phonons in a thin gold foil. The decaying events locally modify the temperature
      of the liquid-solid interface, establishing microscale thermal gradients of
      sufficient magnitude for the droplet to undergo thermocapillary flow. We present
      experimental evidence of such gradients resulting in local surface modification
      associated with the excitation of surface plasmons. We show theoretically that
      the observed effect is due to Marangoni forces, and computationally visualize the
      flow characteristics for the experimental parameters. As an application based on
      our results, we propose a method for an all-optical modulation of light by light
      mediated by the droplet oscillations. Furthermore, the results have important
      consequences for microfluidics, droplet actuation, and simultaneous surface
      plasmon resonance sensing and spectroscopy.

PMID- 16906981
TI  - Magnetoviscosity in suspensions of grains with finite magnetic anisotropy.
AB  - Coupling between magnetic and mechanical rotational degrees of freedom of fine
      ferromagnetic grains is provided by the energy of their magnetic anisotropy. In
      the limiting case of strong anisotropy, an applied stationary magnetic field
      induces the greatest obstacles to the "rigid dipole" spin in a vortex ferrofluid
      flow, while in the opposite ideal case, the "soft dipoles" twist freely with the
      liquid. As a result, the field-dependent part of the ferrofluids viscosity
      depends not only on the external magnetic field strength but also on the particle
      magnetic anisotropy. An explicit expression coming from simple physical arguments
      and describing both these dependencies of magnetoviscosity is derived and
      discussed.

PMID- 16906982
TI  - Recombination and population inversion in plasmas generated by tunneling
      ionization.
AB  - Above-threshold ionization (ATI) ionization by linearly polarized light has been
      proposed by several authors as a means of driving recombination lasers in the
      soft x-ray spectral region. The pump radiation generates a cold electron plasma
      with ions in a single ionization stage, which is an ideal starting condition for
      strong recombination. Population inversions form during the recombination cascade
      to the ground state of the next ionization stage. In the absence of any
      relaxation the electron distribution is strongly peaked near zero energy.
      However, a number of different processes all heat the cold electrons towards
      Maxwellian, and may thereby reduce the recombination rate in the higher levels.
      Using numerical models we investigate these relaxation processes and their effect
      on recombination. We show that the recombination can be well described by the
      standard cascade model, provided an appropriate temperature is used. We examine
      two cases in detail, hydrogen-like lithium where the inversion is with respect to
      the ground state, and lithium-like nitrogen where it is with the first excited
      state. The two cases differ markedly in the degree of relaxation achieved, and in
      the duration of the population inversion.

PMID- 16906983
TI  - Method to find the electron distribution function from cylindrical probe data.
AB  - Druyvesteyn's method finds the distribution of electron speeds from the second
      derivative of probe data using the assumption that the distribution is
      spherically symmetric. For the disk probe, the data are more directly related to
      the velocity distribution projected onto the direction normal to the probe
      surface. The projected distribution is less sensitive to noise because it is
      related to the first derivative of the data rather than the second. For the
      cylindrical probe, the data are more directly related to the distribution of
      energies projected onto the plane perpendicular to the probe axis. A method is
      developed for recovering this projected distribution from digitized probe data.
      The method is mathematically more complex than Druyvesteyn's method, but has the
      advantage of being less sensitive to noise. The methods are compared using noise
      free simulated data and using noisy data from a double-plasma device with
      multidipolar magnetic confinement.

PMID- 16906984
TI  - X-ray spectroscopy of 1 cm plasma channels produced by self-guided pulse
      propagation in elongated cluster jets.
AB  - We diagnose the self-channeled propagation of intense femtosecond pulses over an
      extended distance in a N2O cluster gas target using high resolution kilovolt x
      ray pinhole images of the channel and spatially resolved x-ray spectra. The x-ray
      images are consistent with femtosecond optical scattering, shadowgraphy, and
      interferometry images. We observe extended plasma channels (approximately 9 mm)
      limited either by the cluster jet length or by absorption, for injected laser
      intensities in the range of 10(16)-10(17) W/cm2. Spectral line shapes for the
      OVII 1s2-1s3p and OVIII 1s-2p transitions (at 1.8627 and 1.8969 nm, respectively)
      show significant broadening to the blue side and with truncated emission on the
      red side. We attribute this effect to Doppler blueshifted emission from fast ions
      from exploding clusters moving toward the spectrometer; redshifted emission from
      the opposite side of the cluster is absorbed.

PMID- 16906985
TI  - Spectroscopic characterization of an ultrashort-pulse-laser-driven Ar cluster
      target incorporating both Boltzmann and particle-in-cell models.
AB  - A model that solves simultaneously both the electron and atomic kinetics was used
      to generate a synthetic He alpha and satellite x-ray spectra to characterize a
      high intensity ultrashort laser driven Ar cluster target experiment. In
      particular, level populations were obtained from a detailed collisional-radiative
      model where collisional rates were computed from a time varying electron
      distribution function obtained from the solution of the zero-dimensional
      Boltzmann equation. In addition, a particle-in-cell simulation was used to model
      the laser interaction with the cluster target and provided the initial electron
      energy distribution function (EEDF) for the Boltzmann solver. This study suggests
      that a high density average, <Na>high, of 3.2 x 10(20) cm(-3) was held by the
      system for a time, delta tau, of 5.7 ps, and during this time the plasma was in a
      highly nonequilibrium state in both the EEDF and the ion level populations.

PMID- 16906986
TI  - Current-free double-layer formation in inductively coupled plasma in a uniform
      magnetic field.
AB  - The axial profiles of plasma parameters for low and moderate pressures, such as
      the plasma potential, electron temperature, and number density, have been
      evaluated in magnetized inductively coupled plasma. The experimental results
      revealed in both cases the existence of a genuine current-free double-layer
      structure, separating two plasma regions with different properties. Based on the
      experimental results, a physical scenario for the self-assembling of the double
      layer is proposed. Also, the axial profile of the electron number density
      downstream is analyzed, emphasizing the role of neutral metastable ionization,
      and a simple analytical model is developed to fit the experimental data. The
      model allows the estimation of neutral metastable number density downstream and
      the recombination rate coefficient.

PMID- 16906987
TI  - Collisional absorption in aluminum.
AB  - The interaction of ultrashort laser pulses with matter is a topic of growing
      interest. In particular, recent developments on free-electron lasers have opened
      an unexplored field in which many interesting physical phenomena are to be
      expected. Since hydrodynamic descriptions of the interaction process need a
      microscopic "input," a quantum statistical theory of energy absorption by matter
      is required. We present a kinetic theory of collisional absorption in dense
      plasmas and analyze the electron-ion collision frequency in warm dense aluminum
      in dependence on laser frequency and temperature.

PMID- 16906988
TI  - Statistical analysis of the chaotic optical field from a self-amplified
      spontaneous-emission free-electron laser.
AB  - We use Rice's theory of shot noise random processes to provide a statistical
      analysis of the evolution of the amplitude and phase of the chaotic optical field
      from a high-gain, self-amplified, spontaneous-emission (SASE) free-electron
      laser. The theoretical framework developed is compared with recent frequency
      resolved optical-gating measurements of the SASE output at the LEUTL facility at
      Argonne National Laboratory.

PMID- 16906989
TI  - Laser acceleration of electrons to giga-electron-volt energies using highly
      charged ions.
AB  - The recent proposal to use highly charged ions as sources of electrons for laser
      acceleration [S. X. Hu and A. F. Starace, Phys. Rev. Lett. 88, 245003 (2002)] is
      investigated here in detail by means of three-dimensional, relativistic Monte
      Carlo simulations for a variety of system parameters, such as laser pulse
      duration, ionic charge state, and laser focusing spot size. Realistic laser
      focusing effects--e.g., the existence of longitudinal laser field components-are
      taken into account. Results of spatial averaging over the laser focus are also
      presented. These numerical simulations show that the proposed scheme for laser
      acceleration of electrons from highly charged ions is feasible with current or
      near-future experimental conditions and that electrons with GeV energies can be
      obtained in such experiments.

PMID- 16906990
TI  - Experimental studies of the magnetized friction force.
AB  - High-energy electron cooling, presently considered as an essential tool for
      several applications in high-energy and nuclear physics, requires an accurate
      description of the friction force which ions experience by passing through an
      electron beam. Present low-energy electron coolers can be used for a detailed
      study of the friction force. In addition, parameters of a low-energy cooler can
      be chosen in a manner to reproduce regimes expected in future high-energy
      operation. Here, we report a set of dedicated experiments in CELSIUS aimed at a
      detailed study of the magnetized friction force. Some results of the accurate
      comparison of experimental data with the friction force formulas are presented.

PMID- 16906991
TI  - Solitary waves in discrete media with four-wave mixing.
AB  - In this paper, we examine in detail the principal branches of solutions that
      arise in vector discrete models with nonlinear intercomponent coupling and four
      wave mixing. The relevant four branches of solutions consist of two single mode
      branches (transverse electric and transverse magnetic) and two mixed mode
      branches, involving both components (linearly polarized and elliptically
      polarized). These solutions are obtained explicitly and their stability is
      analyzed completely in the anticontinuum limit (where the nodes of the lattice
      are uncoupled), illustrating the supercritical pitchfork nature of the
      bifurcations that give rise to the latter two, respectively, from the former two.
      Then the branches are continued for finite coupling constructing a full two
      parameter numerical bifurcation diagram of their existence. Relevant stability
      ranges and instability regimes are highlighted and, whenever unstable, the
      solutions are dynamically evolved through direct computations to monitor the
      development of the corresponding instabilities. Direct connections to the earlier
      experimental work of Meier [Phys. Rev. Lett., 91, 143907 (2003)] that motivated
      the present work are given.

PMID- 16906992
TI  - Joint time-frequency and finite-difference time-domain analysis of precursor
      fields in dispersive media.
AB  - Superluminal group velocities, defined as group velocities exceeding the speed of
      light in vacuum, c, have been theoretically predicted and experimentally observed
      in various types of dispersive media, such as passive and active Lorentzian
      media, one-dimensional photonic crystals, and undersized waveguides. Though
      superluminal group velocities have been found in these media, it has been
      suggested that the pulse "front" and associated transient field oscillations,
      known as the precursors or forerunners, will never travel faster than c, and
      hence relativistic causality is always preserved. Until now, few rigorous studies
      of these transient fields in structures exhibiting superluminal group velocities
      have been performed. In this paper, we present the dynamic evolution of these
      earliest field oscillations in one-dimensional photonic crystals (1DPC), using
      finite-difference time-domain (FDTD) techniques in conjunction with joint time
      frequency analysis (JTFA). Our study clearly shows that the precursor fields
      associated with superluminal pulse propagation travel at subluminal speeds, and
      thus, the arrival of these precursor fields must be associated with the arrival
      of "genuine information." Our study demonstrates the expected result that
      abnormal group velocities do not contradict Einstein causality. This work also
      shows that FDTD analysis and JTFA can be combined to study the dynamic evolution
      of the transient and steady state pulse propagation in dispersive media.

PMID- 16906993
TI  - Stability of two-dimensional spatial solitons in nonlocal nonlinear media.
AB  - We discuss the existence and stability of two-dimensional solitons in media with
      spatially nonlocal nonlinear response. We show that such systems, which include
      thermal nonlinearity and dipolar Bose-Einstein condensates, may support a variety
      of stationary localized structures, including rotating dipole solitons. We also
      demonstrate that the stability of these structures critically depends on the
      spatial profile of the nonlocal response function.

PMID- 16906994
TI  - Acoustic quasimodes in two-dimensional dispersed random media.
AB  - Using the generalized coherent-potential-approximation approach, we present the
      dispersion relation of the two-dimensional dispersed random media. In the
      intermediate-frequency regime, two acoustic modes are found in colloidal
      suspensions including cylindrical plastic rod in water background. The scattering
      cross section offers a good explanation for the two modes and the observed
      frequency gaps in the excitation spectra.

PMID- 16906995
TI  - Dynamics of two-dimensional coherent structures in nonlocal nonlinear media.
AB  - We study stability and dynamics of the single cylindrically symmetric solitary
      structures and dipolar solitonic molecules in spatially nonlocal media. The main
      properties of the solitons, vortex solitons, and dipolar solitons are
      investigated analytically and numerically. The vortices and higher-order solitons
      show the transverse symmetry-breaking azimuthal instability below some critical
      power. We find the threshold of the vortex soliton stabilization using the linear
      stability analysis and direct numerical simulations. The higher-order solitons,
      which have a central peak and one or more surrounding rings, are also
      demonstrated to be stabilized in nonlocal nonlinear media. Using direct numerical
      simulations, we find a class of radially asymmetric, dipolelike solitons and show
      that, at sufficiently high power, these structures are stable.

PMID- 16906996
TI  - Rational solitons in deep nonlinear optical Bragg grating.
AB  - We have examined the rational solitons in the Generalized Coupled Mode model for
      a deep nonlinear Bragg grating. These solitons are the degenerate forms of the
      ordinary solitons and appear at the transition lines in the parameter plane. A
      simple formulation is presented for the investigation of the bifurcations induced
      by detuning the carrier wave frequency. The analysis yields among others the
      appearance of in-gap dark and antidark rational solitons unknown in the nonlinear
      shallow grating. The exact expressions for the corresponding rational solitons
      are also derived in the process, which are characterized by rational algebraic
      functions. It is further demonstrated that certain effects in the soliton energy
      variations are to be expected when the frequency is varied across the values
      where the rational solitons appear.

PMID- 16906997
TI  - Dynamics of a spheroidal particle in a leaky dielectric medium in an ac electric
      field.
AB  - We study a system comprising a spheroidal particle with permittivity epsilon 2
      and conductivity sigma 2 immersed in a host medium with permittivity epsilon 1
      and conductivity sigma 1 in the ac external electric field with a strength
      Epsilon 0 and frequency omega. We determined conditions when orientation of a
      spheroidal particle with a finite electric conductivity at t --> infinity
      coincides with the orientation of the ideal dielectric spheroidal particle, when
      orientation of a spheroid at t --> infinity is normal to the orientation of the
      ideal dielectric spheroidal particle, and when orientation of particle is not
      affected by the external electric field. We found the direct connection between
      the final orientation of the particle and the existence of two time intervals,
      T1(omega) and T2(omega), such that during time interval T1 an equilibrium
      orientation of the particle is the same as the equilibrium orientation of an
      ideal dielectric particle while during time interval T2 the direction of the
      stable equilibrium orientation is normal to the equilibrium orientation of an
      ideal dielectric particle. The values T1 and T2 depend on the frequency of the
      external field omega and T = T1(omega) + T2(omega), where T=2 pi/omega.

PMID- 16906998
TI  - Stable stationary and quasiperiodic discrete vortex breathers with topological
      charge S = 2.
AB  - We demonstrate the stability of a stationary vortex breather with vorticity S = 2
      in the two-dimensional discrete nonlinear Schrodinger model for a square lattice
      and also discuss the effects of exciting internal sites in a vortex ring. We also
      point out the fundamental difficulties of observing these solutions with current
      experimental techniques. Instead, we argue that relevant initial conditions will
      lead to the formation of quasiperiodic vortex breathers.

PMID- 16906999
TI  - Opening up complete photonic bandgaps in three-dimensional photonic crystals
      consisting of biaxial dielectric spheres.
AB  - In this paper, the scattering matrix of sphere with dielectric biaxial anisotropy
      is obtained exactly within the framework of the extended Mie theory. By
      incorporating the scattering matrix into the multiple scattering method, we study
      theoretically the photonic band structure of three dimensional photonic crystals
      consisting of biaxial dielectric spheres. Our results demonstrate that complete
      photonic bandgaps can be found in both fcc and sc lattice structures, which are
      absent in photonic crystals composed of isotropic dielectric spheres. Moreover we
      have compared our results with those coming from the photonic crystals consisting
      of the uniaxially birefringent dielectric spheres. It is found that because of
      the enhancement of the anisotropy, the degeneracy is lifted further, resulting in
      two neighboring photonic bandgaps, the lower one is complete while the upper one
      is partial existing only in some special regions of the first Brillouin zone.

PMID- 16907000
TI  - Exact soliton-on-plane-wave solutions for two-component Bose-Einstein
      condensates.
AB  - By means of the Darboux transformation, we obtain analytical solutions for a
      soliton set on top of a plane-wave background in coupled Gross-Pitaevskii
      equations describing a binary Bose-Einstein condensate. We consider basic
      properties of the solutions with and without the cross interaction [cross phase
      modulation (XPM)] between the two components of the background. In the absence of
      the XPM, this solutions maintain properties of one-component condensates, such as
      the modulation instability (MI); in the presence of the cross interaction, the
      solutions exhibit different properties, such as restriction of the MI and soliton
      splitting.

PMID- 16907001
TI  - Interaction of solitons with segments with modified dispersion.
AB  - The interaction of nonlinear Schrodinger solitons with extended inhomogeneities
      with modified group-velocity (GV) and group-velocity dispersion (GVD)
      coefficients is investigated numerically. Increased GVD coefficients act as
      potential barriers and yield reflection or transmission of the incoming soliton.
      Decreased GVD coefficients act as potential wells, and for a given range of
      parameters the scattering results exhibit periodically repeating windows of
      trapping and transmission as a function of the length of the segment. It is shown
      that the escape of the soliton is due to a resonance between the period of the
      shape oscillations of the soliton inside the segment and the length of the
      latter. Segments with modified GV coefficients act as potential wells for both
      positive and negative values of the GV mismatch and can also lead to periodic
      capture-transmission scattering patterns.

PMID- 16907002
TI  - Emergence and control of breather and plasma oscillations by synchronizing
      perturbations.
AB  - Large amplitude standing waves of spatially periodic sine-Gordon equations are
      excited and controlled by sweeping the frequency of a small, spatially modulated
      driving oscillation through resonances in the system. The approach is based on
      capturing the system into resonances and subsequent adiabatic, persistent phase
      locking (autoresonance) yielding control via a single external parameter (the
      driving frequency). Plasma oscillations in the system are excited by using a
      small amplitude drive in the form of a chirped frequency standing wave, while
      emergence of autoresonant breather oscillations requires driving by a combination
      of small amplitude oscillation and standing waves.

PMID- 16907003
TI  - Optical breathers in nonlinear anisotropic and dispersive media.
AB  - Anisotropic crystals containing impurity atoms, when the principal optical axis
      of the uniaxial crystal and the vector of electrical dipole moment of the
      impurity atoms are perpendicular to each other and are directed along different
      crystallographic axes, are shown to have three different mechanisms of the
      formation of breathers depending on the direction of the wave propagation and on
      the symmetry of the medium. Explicit analytic expressions for the parameters of
      breathers and the effective nonlinear susceptibilities for extraordinary waves
      are obtained. All uniaxial crystals with quadratic susceptibilities can be
      divided into three different groups, according to the crystal classes. Each group
      is characterized by a universal structure of the breather zones. The structure of
      the breather zones of the trigonal, tetragonal, and hexagonal crystals with cubic
      susceptibilities depends neither on the crystallographic system nor on the
      crystal classes and coincides with the structure of the breather zones of the
      trigonal and hexagonal crystals with quadratic susceptibilities and crystal
      classes 3, 3m, 6, 6m2. It is shown that structure of breather zones of the
      different groups of crystals for the cases when the principal optical axis of the
      uniaxial crystal and the vector of electrical dipole moment of the impurity atoms
      are mutual parallel or perpendicular to each other are significantly different.

PMID- 16907004
TI  - Bound whispering gallery modes in circular arrays of dielectric spherical
      particles.
AB  - Low-dimensional ordered arrays of optical elements can possess bound modes having
      an extremely high quality factor. Typically, these arrays consist of metal
      elements which have significantly high light absorption thus restricting
      performance. In this paper we address the following question: can bound modes be
      formed in dielectric systems where the absorption of light is negligible? Our
      investigation of circular arrays of spherical particles shows that (1) high
      quality modes in an array of ten or more particles can be attained at least for a
      refractive index n(r) > 2, so optical materials like TiO2 or GaAs can be used;
      (2) the most bound modes have nearly transverse polarization perpendicular to the
      circular plane; (3) in a particularly interesting case of TiO2 particles (rutile
      phase, n(r) = 2.7), the quality factor of the most bound mode increases almost by
      an order of magnitude with the addition of ten extra particles, while for
      particles made of GaAs the quality factor increases by almost two orders of
      magnitude with the addition of ten extra particles. We hope that this preliminary
      study will stimulate experimental investigations of bound modes in low
      dimensional arrays of dielectric particles.

PMID- 16907005
TI  - Soliton-radiation beat analysis.
AB  - A technique is introduced which allows us to extract information on the solitonic
      content from a nonlinear wave. Its applicability is not as narrowly restricted as
      that of inverse scattering theory; therefore, it works in situations that could
      not be studied before. As an example we identify and demonstrate a higher order
      dispersion-managed soliton.

PMID- 16907006
TI  - Effective-medium theory for energy velocity in one-dimensional finite lossless
      photonic crystals.
AB  - The effective medium theory is a useful approach for investigating the
      electromagnetic wave propagation in periodic multilayer slabs. It allows accurate
      computation of transmission and reflection spectra as well as of phase and group
      velocities. In this paper we derive an exact analytical expression for the energy
      velocity of a one-dimensional finite photonic crystal based on the effective
      medium approach. It accounts for the multiple reflections within the structure
      which results in the characteristic oscillations of the transmission spectrum.
      Our analytical expression holds for an arbitrary refractive index contrast and
      goes beyond the limits of the standard homogenization method. In order to
      validate our approach, results obtained by using the all-frequency effective
      energy velocity have been compared to those obtained using the transfer matrix
      method.

PMID- 16907007
TI  - Diffraction-arrested soliton self-frequency shift of few-cycle laser pulses in a
      photonic-crystal fiber.
AB  - The balance between diffraction and index-step guiding in photonic-crystal fibers
      is controlled by modifying the fiber structure, leading to different wavelength
      dependences of the effective mode area and providing a mechanism to control
      nonlinear-optical phenomena. In optical fibers with a steep profile, the guided
      mode of the light field tends to become much less compact with an increase in
      radiation wavelength, slowing down the Raman-induced soliton self-frequency shift
      of an ultrashort laser pulse. A reduction of the soliton self-frequency shift is
      demonstrated for input laser pulses.

PMID- 16907008
TI  - Pulse compression and multimegawatt optical solitons in hollow photonic-crystal
      fibers.
AB  - Solitonic phenomena in hollow photonic-crystal fibers are shown to offer new
      solutions for the control, transmission, and spectral-temporal transformation of
      ultrashort high-power laser pulses. With the initial parameters of laser
      radiation accurately matched with fiber dispersion and nonlinearity,
      submicrojoule laser pulses are shown to exhibit a self-compression and soliton
      dynamics in the regime of anomalous dispersion. Regimes of solitonic pulse
      evolution giving rise to few-cycle field waveforms are demonstrated. Based on
      simple arguments of soliton theory, we derive semiempirical relations providing
      interesting insights into the minimum pulse width of the laser field in a hollow
      photonic-crystal fiber as a function of the input laser energy.

PMID- 16907009
TI  - Analytical solitary wave solutions of the nonlinear Kronig-Penney model in
      photonic structures.
AB  - A phase space method is employed for the construction of analytical solitary wave
      solutions of the nonlinear Kronig-Penney model in a photonic structure. This
      class of solutions is obtained under quite generic conditions, while the method
      is applicable to a large variety of systems. The location of the solutions on the
      spectral band gap structure as well as on the low dimensional space of system's
      conserved quantities is studied, and robust solitary wave propagation is shown.

PMID- 16907010
TI  - Equivalence of the virtual-source method and wave-field deconvolution in seismic
      interferometry.
AB  - Seismic interferometry and the virtual-source method are related approaches for
      extracting the Green's function that accounts for wave propagation between
      receivers by making suitable combinations of the waves recorded at these two
      receivers. These waves can either be excited by active, controlled, sources, or
      by natural incoherent sources. We compare this technique with the deconvolution
      of the wave field recorded at different receivers. We show that the deconvolved
      wave field is a solution of the same wave equation as that for the physical
      system, but that the deconvolved wave forms may satisfy different boundary
      conditions than those of the original system. We apply this deconvolution
      approach to the wave motion recorded at various levels in a building after an
      earthquake, and show how to extract the building response for different boundary
      conditions. Extracting the response of the system with different boundary
      conditions can be used to enhance, or suppress, the normal-mode response. In
      seismic exploration this principle can be used for the suppression of surface
      related multiples.

PMID- 16907011
TI  - Discrete soliton ratchets driven by biharmonic fields.
AB  - Directed motion of topological solitons (kinks or antikinks) in the damped and ac
      driven discrete sine-Gordon system is investigated. We show that if the driving
      field breaks certain time-space symmetries, the soliton can perform
      unidirectional motion. The phenomenon resembles the well known effects of ratchet
      transport and nonlinear harmonic mixing. Direction of the motion and its velocity
      depends on the shape of the ac drive. Necessary conditions for the occurrence of
      the effect are formulated. In comparison with the previously studied continuum
      case, the discrete case shows a number of new features: nonzero depinning
      threshold for the driving amplitude, locking to the rational fractions of the
      driving frequency, and diffusive ratchet motion in the case of weak intersite
      coupling.

PMID- 16907012
TI  - Form factor in persistent hole burning in multiple scattering optical media.
AB  - This paper presents detailed experiments on persistent hole burning in
      photoreactive and multiple scattering media. The dependence of the hole shape and
      width on the sample thickness, transport mean free path, and absorption length
      was measured. The experimental results show good agreement with a previously
      reported theoretical calculation on the basis of a diffusion approximation [Phys.
      Rev. E 70, 046606 (2004)].

PMID- 16907013
TI  - Delayed scattering of solitary waves from interfaces in a granular container.
AB  - In granular media, the characterization of the behavior of solitary waves around
      interfaces is of importance in order to look for more applications of these
      systems. We study the behavior of solitary waves at both interfaces of a
      symmetric granular container, a class of systems that has received recent
      attention because it possesses the feature of energy trapping. Hertzian contact
      is assumed. We have found that the scattering process is elastic at one
      interface, while at the other interface it is observed that the transmitted
      solitary wave has stopped its movement during a time that gets longer when the
      ratio between masses at the interfaces increases. The origin of this effect can
      be traced back to the phenomenon of gaps opening, recently observed
      experimentally.

PMID- 16907014
TI  - Topological filters and high-pass/low-pass devices for solitons in inhomogeneous
      networks.
AB  - We show that, by inserting suitable finite networks at a site of a chain, it is
      possible to realize filters and high-pass/low-pass devices for solitons
      propagating along the chain. The results are presented in the framework of
      coupled optical waveguides; possible applications to different contexts, such as
      photonic lattices and Bose-Einstein condensates in optical networks are also
      discussed. Our results provide a first step in the control of the soliton
      dynamics through the network topology.

PMID- 16907015
TI  - Optical properties of two-dimensional negative-phase-velocity-medium photonic
      crystals.
AB  - By an extended plane-wave-based transfer-matrix method, the photonic band
      structure and the corresponding transmission spectrum have been calculated for a
      two-dimensional photonic crystal composed of negative-phase-velocity-medium
      (NPVM) cylindrical rods. Dispersionless anticrossing bands in the two-dimensional
      NPVM periodic structure are generated by the couplings among surface polaritons
      localized in the NPVM rods. In part of the negative-phase-velocity frequency
      region, the photonic band structures of the NPVM photonic crystal are
      characterized by a topographical continuous dispersion relationship accompanied
      by many anticrossing bands. The effect of the filling fraction of the NPVM rods
      on the optical properties of photonic crystals has also been studied.

PMID- 16907016
TI  - Anharmonicity and its significance to non-Ohmic electric conduction.
AB  - We provide here a thorough analysis of the interplay between anharmonic lattice
      dynamics (with exponential repulsion between units) and electric conduction in a
      driven-dissipative electrically charged one-dimensional system. First, we
      delineate the ranges of parameter values where, respectively, subsonic and
      supersonic wave solitons are possible along the lattice. Then, we study the
      consequences of the soliton-mediated coupling of light negative to heavy positive
      charges (lattice units). In the presence of an external electric field we obtain
      the current-field characteristics for a wide range of values of all parameters
      defining the system. Finally, we discuss the conditions for an Ohmic-non-Ohmic
      transition of the electric current as the electric field strength is varied.

PMID- 16907017
TI  - Adaptive resolution scheme for efficient hybrid atomistic-mesoscale molecular
      dynamics simulations of dense liquids.
AB  - The adaptive resolution scheme (AdResS) for efficient hybrid particle-based
      atomistic/mesoscale molecular dynamics (MD) simulations recently introduced by
      us, [J. Chem. Phys. 123, 224106 (2005)] is extended to high density molecular
      liquids with spherical boundaries between the atomistic and mesoscale regions.
      The key feature of this approach is that it allows for a dynamical change of the
      number of molecular degrees of freedom during the course of a MD simulation by an
      on-the-fly switching between the atomistic and mesoscopic levels of detail.
      Pressure and density variations occurring at the atomistic/mesoscale boundary in
      the original version are considerably reduced employing the improved methodology
      presented here.

PMID- 16907018
TI  - Numerical method for coherent electron dynamics with position-dependent effective
      mass distributions in semiconductor heterostructures.
AB  - We develop a numerical scheme for solving the time-dependent Kohn-Sham equation
      in semiconductor heterostructures. Based on the efficient and accurate method
      recently proposed by Watanabe and Tsukada [Phys. Rev. E 65, 036705 (2002)], an
      extension is made for treating effective-mass mismatch between different
      semiconductor materials. A demonstrative calculation shows that the energy of the
      quantum-well state is accurately conserved during the time-evolution calculation
      with the present method. Examples under the existence of Hartree and exchange
      correlation interactions are also shown as demonstrations of nonlinear electron
      dynamics in quantum wells. The present method is particularly useful for
      analyzing nonlinear coherent charge oscillations in semiconductor quantum wells,
      taking into account many-body effects.

PMID- 16907019
TI  - Mesoscopic interparticle potentials in the lattice Boltzmann equation for
      multiphase fluids.
AB  - I introduce a method to derive mesoscopic particle interactions by macroscopic
      thermodynamics, which is suitable for simulation of multiphase fluids by means of
      the lattice Boltzmann equation. For van der Waals fluids, the interaction
      possesses a high-density strong repulsive core and a low-density weak attractive
      tail, which looks like the Lennard-Jones potential with replacement of the
      distance between particles with mass density. Numerical results on phase
      separation show a droplet growth scheme rather than spinodal decomposition, and
      exhibit accurately the equilibrium phase diagram, a convincing interfacial energy
      property, and irreversible thermodynamics.

PMID- 16907021
TI  - Cascaded digital lattice Boltzmann automata for high Reynolds number flow.
AB  - Lattice Boltzmann methods are of limited applicability for direct numerical
      simulation of turbulent flow due to instabilities in the zero viscosity limit. We
      observe that this is caused by an insufficient degree of Galilean invariance of
      the relaxation-type Lattice Boltzmann collision operator. The cascaded digital
      lattice Boltzmann automata described here, provides a method with which to
      achieve stable collision operators down to the limit of zero viscosity.

PMID- 16907020
TI  - Consistent thermodynamic derivative estimates for tabular equations of state.
AB  - A valid fluid equation of state (EOS) must satisfy the thermodynamic conditions
      of consistency (derivation from a free energy) and stability (positive sound
      speed squared). Numerical simulations of compressible fluid flow for realistic
      materials require a tabular EOS, but typical software interfaces to such tables
      based on polynomial or rational interpolants may enforce the stability
      conditions, but do not enforce the consistency condition and its derivatives. The
      consistency condition is important for the computation of various dimensionless
      parameters of an EOS that may involve derivatives of up to second order which are
      important for the development of more sensitive artificial viscosities and
      Riemann solvers that accurately model shock structure in regions near phase
      transitions. We describe a table interface based on the tuned regression method,
      which is derived from a constrained local least-squares regression technique. It
      is applied to several SESAME EOS showing how the consistency and stability
      conditions can be satisfied to round-off while computing first and second
      derivatives with demonstrated second-order convergence. An improvement of 14
      orders of magnitude over conventional derivatives is demonstrated, although the
      method is apparently two orders of magnitude slower, due to the fact that every
      evaluation requires solving an 11-dimensional nonlinear system. Application is
      made to the computation of the fundamental derivative.

PMID- 16907022
TI  - Numerical treatment of the dynamics of a conserved order parameter in the
      presence of walls.
AB  - We discuss how the diffusive dynamics of a conserved order parameter should be
      numerically treated when impenetrable wall surfaces are present and interact with
      the degrees of freedom characterized by the order parameter. We derive the
      discretization scheme for the dynamics, paying particular attention to the
      conservation of the order parameter in the strict numerical sense. The
      discretized chemical potential, or the functional derivative of the free energy,
      contains a surface contribution inversely proportional to the grid spacing Delta
      z, which was proposed heuristically in a recent paper of Henderson and Clarke
      [Macromol. Theory Simul. 14, 435 (2005)]. Although apparently that surface
      contribution diverges in the continuum limit Delta z --> 0, we can show, by an
      analytic argument and numerical calculations, that this divergence does not yield
      any anomalies, and that our discretization scheme is well defined in this limit.
      We also discuss the correspondence of our treatment to the model proposed by Puri
      and Binder [Phys. Rev. A 46, R4487 (1992)] extensively used for the present
      problem.

PMID- 16907023
TI  - Solving the Fokker-Planck kinetic equation on a lattice.
AB  - We propose a discrete lattice version of the Fokker-Planck kinetic equation in
      close analogy with the lattice-Boltzmann scheme. Our work extends an earlier one
      dimensional formulation to arbitrary spatial dimension D. A generalized Hermite
      Gauss procedure is used to construct a discretized kinetic equation and a Chapman
      Enskog expansion is applied to adapt the scheme so as to correctly reproduce the
      macroscopic continuum equations. The linear stability of the algorithm with
      respect to the finite time step Delta t is characterized by the eigenvalues of
      the collision matrix. A heuristic second-order algorithm in Delta t is applied to
      investigate the time evolution of the distribution function of simple model
      systems, and compared to known analytical solutions. Preliminary investigations
      of sedimenting Brownian particles subjected to an orthogonal centrifugal force
      illustrate the numerical efficiency of the Lattice-Fokker-Planck algorithm to
      simulate nontrivial situations. Interactions between Brownian particles may be
      accounted for by adding a standard Bhatnagar-Gross-Krook collision operator to
      the discretized Fokker-Planck kernel.

PMID- 16907024
TI  - Extended volumetric scheme for lattice Boltzmann models.
AB  - An extended volumetric scheme is proposed for lattice Boltzmann (LB) models. This
      scheme is particularly desirable for multispeed LB models due to its removal of
      nonlocal advection. It recovers the same macroscopic hydrodynamics as the
      standard lattice Boltzmann method without any further treatments. This scheme
      achieves an effectively reduced Courant-Friedrichs-Lewy number so that numerical
      stability is significantly enhanced for high Reynolds number simulations while
      maintaining the same order of numerical accuracy.

PMID- 16907025
TI  - Lattice Boltzmann scheme for fluids with dynamic heterogeneities.
AB  - We introduce and discuss a three-dimensional mesoscopic lattice Boltzmann model
      for the numerical simulation of strongly-interacting fluids with dynamic
      inhomogeneities. The model is based on an extension of the standard lattice
      Boltzmann dynamics in which streaming between neighboring lattice sites is
      constrained by the value of the nonlocal density of the surrounding fluid. The
      resulting dynamics exhibits typical features of dynamically heterogeneous fluids,
      such as long-time relaxation, non-Gaussian density distributions and dynamic
      heterogeneities. Due to its intrinsically parallel dynamics and absence of
      statistical noise, the method is expected to compute significantly faster than
      molecular dynamics, Monte Carlo, and lattice glass models.

PMID- 16907026
TI  - Slip-flow boundary condition for straight walls in the lattice Boltzmann model.
AB  - A slip-flow boundary condition has been developed in the lattice Boltzmann model
      combining an interpolation method and a simple slip boundary condition for
      straight walls placed at arbitrary distance from the last fluid node. An
      analytical expression has been derived to connect the model parameters with the
      slip velocity for Couette and Poiseuille flows in the nearly continuum limit. The
      proposed interpolation method ensures that the slip velocity is independent of
      the wall position in first order of the Knudsen number. Computer simulations have
      been carried out to validate the model. The Couette and Poiseuille flows agree
      with the analytical results to machine order. Numerical simulation of a moving
      square demonstrates the accuracy of the model for walls moving in both the
      tangential and normal directions.

PMID- 16907027
TI  - Accelerated multiboson algorithm for Coulomb gases with dynamical dielectric
      effects.
AB  - A recent reformulation [Phys. Rev. E 73, 016705 (2006)] of the problem of Coulomb
      gases in the presence of a dynamical dielectric medium showed that finite
      temperature simulations of such systems can be accomplished on the basis of
      completely local Hamiltonians on a spatial lattice by including additional
      bosonic fields. For large systems, the Monte Carlo algorithm proposed in the
      above-cited work becomes inefficient due to a low acceptance rate for particle
      moves in a fixed background multiboson field. We show here how this problem can
      be circumvented by use of a coupled particle-multiboson update procedure that
      improves acceptance rates on large lattices by orders of magnitude. The method is
      tested on a one-component plasma with neutral dielectric particles for a variety
      of system sizes.

PMID- 16907028
TI  - Bidding process in online auctions and winning strategy: Rate equation approach.
AB  - Online auctions have expanded rapidly over the last decade and have become a
      fascinating new type of business or commercial transaction in this digital era.
      Here we introduce a master equation for the bidding process that takes place in
      online auctions. We find that the number of distinct bidders who bid k times up
      to the tth bidding progresses, called the k-frequent bidder, seems to scale as
      n(k)(t) approximately tk(-2.4). The successfully transmitted bidding rate by the
      k-frequent bidder is likely to scale as q(k)(t) approximately k(-1.4),
      independent of t for large t. This theoretical prediction is close to empirical
      data. These results imply that bidding at the last moment is a rational and
      effective strategy to win in an eBay auction.

PMID- 16907029
TI  - Linear response to perturbation of nonexponential renewal process: A generalized
      master equation approach.
AB  - The work by Barbi, Bologna, and Grigolini [Phys. Rev. Lett. 95, 220601 (2005)]
      discusses a response to alternating external field of a non-Markovian two-state
      system, where the waiting time between the two attempted changes of state follows
      a power law. It introduced a new instrument for description of such situations
      based on a stochastic master equation with reset. In the present Brief Report we
      provide an alternative description of the situation within the framework of a
      generalized master equation. The results of our analytical approach are
      corroborated by direct numerical simulations of the system.

PMID- 16907030
TI  - Cooperation in the noisy case: Prisoner's dilemma game on two types of regular
      random graphs.
AB  - We have studied an evolutionary prisoner's dilemma game with players located on
      two types of random regular graphs with a degree of 4. The analysis is focused on
      the effects of payoffs and noise (temperature) on the maintenance of cooperation.
      When varying the noise level and/or the highest payoff, the system exhibits a
      second-order phase transition from a mixed state of cooperators and defectors to
      an absorbing state where only defectors remain alive. For the random regular
      graph (and Bethe lattice) the behavior of the system is similar to those found
      previously on the square lattice with nearest neighbor interactions, although the
      measure of cooperation is enhanced by the absence of loops in the connectivity
      structure. For low noise the optimal connectivity structure is built up from
      randomly connected triangles.

PMID- 16907031
TI  - Classical limit of master equation for a harmonic oscillator coupled to an
      oscillator bath with separable initial conditions.
AB  - The Wigner transform of the master equation describing the reduced dynamics of
      the system, of a harmonic oscillator coupled to an oscillator bath, was obtained
      by Karrlein and Grabert [Phys. Rev. E 55, 153 (1997)]. It was shown that for some
      special correlated initial conditions the master equation reduces, in the
      classical limit, to the corresponding classical Fokker-Planck equation obtained
      by Adelman [J. Chem Phys. 64, 124 (1976)]. However, for separable initial
      conditions the Adelman equations were not recovered. We resolve this problem by
      showing that, for separable initial conditions, the classical Langevin equations
      are somewhat different from the one considered by Adelman. We obtain the
      corresponding Fokker-Planck equation and show that they exactly match the
      classical limit of the evolution of the Wigner function obtained from the master
      equation for separable initial conditions. We also discuss why thermal initial
      conditions correspond to Adelman's solution.

PMID- 16907032
TI  - Monin-Lundgren hierarchy versus the Hopf equation in the statistical theory of
      turbulence.
AB  - A functional-differential equation equivalent to the infinitely hierarchic system
      of the coupled equations for many-point velocity distribution functions in
      turbulence established by Monin and Lundgren is presented, to be compared with
      the Hopf characteristic functional equation which governs the time evolution of a
      turbulent velocity field. It turns out that this functional entirely implies the
      Hopf functional, and vice versa. This functional allows us to view turbulence in
      a Lagrangian picture simulated by many-particle dynamics.

PMID- 16907033
TI  - Self-consistent quasiparticle model results for ultrarelativistic electron
      positron thermodynamic plasma.
AB  - Relativistic plasma with two charge species and radiation at thermodynamic
      equilibrium is a general system of interest in astrophysics and high-energy
      physics. We develop a self-consistent quasiparticle model for such a system to
      take account of the collective behavior of plasma, and thermodynamic properties
      are derived. It is applied to the ultrarelativistic electron-positron plasma and
      compared with previous results.

PMID- 16907034
TI  - Comment on "Intermittency exponent of the turbulent energy cascade".
AB  - It is argued that the method used by Cleve et al. [Phys. Rev. E 69, 066316
      (2004)], to determine the intermittency exponent mu is biased at moderate
      Reynolds numbers R lambda. Thus, the claimed dependence of mu upon (R lambda) is
      questionable. Other determinations give a constant value for mu.

PMID- 16907036
TI  - Comment on "Existence of internal modes of sine-Gordon kinks".
AB  - In Phys. Rev. B 42, 2290 (1990) we used a rigorous projection operator collective
      variable formalism for nonlinear Klein-Gordon equations to prove the continuum
      sine-Gordon (SG) equation has a long lived quasimode whose frequency is in the
      continuum just above the lower phonon band edge with a lifetime . We confirmed
      the analytic calculations by simulations which agreed very closely with the
      analytic results. In Phys. Rev. E 62, R60 (2000) the authors performed two
      numerical investigation which they asserted "show that neither intrinsic internal
      modes nor quasimodes exist in contrast to previous results." In this paper we
      prove their first numerical investigation could not possibly observe the
      quasimode in principle and their second numerical investigation actually
      demonstrates the existence of the SG quasimode. Our analytic calculations and
      verifying simulations were performed for a stationary sine-Gordon soliton fixed
      at the origin. Yet the authors in Phys. Rev. E 62, R60 (2000) state the
      explanation of our analytic simulations and confirming simulations are due to the
      Doppler shift of the phonons emitted by our stationary sine-Gordon soliton which
      thus has a zero Doppler shift.

PMID- 16907038
TI  - High-speed observation of the piston effect near the gas-liquid critical point.
AB  - We investigated adiabatic changes in a near-critical fluid on acoustic time
      scales using an ultrasensitive interferometer. A sound emitted by very weak
      continuous heating caused a stepwise adiabatic change at its front with a density
      change of order 10(-7) g/cm(3) and a temperature change of order 10(-5) K. Very
      small heat inputs at a heater produced short acoustic pulses with width of order
      10 micros, which were broadened as they moved through the cell and interacted
      with the boundaries. The pulse broadening became enhanced near the critical
      point. We also examined theoretically how sounds are emitted from a heater and
      how applied heat is transformed into mechanical work. Our predictions agree well
      with our data.

PMID- 16907039
TI  - Coexistence diameter in two-dimensional colloid-polymer mixtures.
AB  - We demonstrate that the law of the rectilinear coexistence diameter in two
      dimensional mixtures of nonspherical colloids and nonadsorbing polymers is
      violated. Upon approach to the critical point, the diameter shows logarithmic
      singular behavior governed by a term t ln t, with t the relative distance from
      the critical point. No sign of a term t2beta could be detected, with beta the
      critical exponent of the order parameter, indicating a very weak or absent Yang
      Yang anomaly. Our analysis thus reveals that nonspherical particle shape alone is
      not sufficient for the formation of a pronounced Yang-Yang anomaly in the
      critical behavior of fluids.

PMID- 16907040
TI  - Stochastic resonance due to internal noise in reaction kinetics.
AB  - We study a reaction model that presents stochastic resonance purely due to
      internal noise. This means that the only source of fluctuations comes from the
      discrete character of the reactants, and no more noises enter into the system.
      Our analysis reveals that the phenomenon is highly complex, and that is generated
      by the interplay of different stochasticity at the three fixed points of a
      bistable system.

PMID- 16907041
TI  - Equilibration through local information exchange in networks.
AB  - We study the equilibrium states of energy functions involving a large set of real
      variables, defined on the links of sparsely connected networks, and interacting
      at the network nodes, using the cavity and replica methods. When applied to the
      representative problem of network resource allocation, an efficient distributed
      algorithm is devised, with simulations showing full agreement with theory.
      Scaling properties with the network connectivity and the resource availability
      are found.

PMID- 16907042
TI  - Nonconcave entropies from generalized canonical ensembles.
AB  - It is well known that the entropy of the microcanonical ensemble cannot be
      calculated as the Legendre transform of the canonical free energy when the
      entropy is nonconcave. To circumvent this problem, a generalization of the
      canonical ensemble that allows for the calculation of nonconcave entropies was
      recently proposed. Here, we study the mean-field Curie-Weiss-Potts spin model and
      show, by direct calculations, that the nonconcave entropy of this model can be
      obtained by using a specific instance of the generalized canonical ensemble known
      as the Gaussian ensemble.

PMID- 16907043
TI  - Interstitial gas and density segregation of vertically vibrated granular media.
AB  - We report experimental studies of the effect of interstitial gas on mass-density
      segregation in a vertically vibrated mixture of equal-sized bronze and glass
      spheres. Sufficiently strong vibration in the presence of interstitial gas
      induces vertical segregation into sharply separated bronze and glass layers. We
      find that the segregated steady state (i.e., bronze or glass layer on top) is a
      sensitive function of gas pressure and viscosity, as well as vibration frequency
      and amplitude. In particular, we identify distinct regimes of behavior that
      characterize the change from bronze-on-top to glass-on-top steady state.

PMID- 16907044
TI  - Simulation study of air-induced segregation of equal-sized bronze and glass
      particles.
AB  - We have investigated the effect of air on the density segregation of fine, equal
      sized bronze and glass particles under vertical sinusoidal vibrations by
      numerical simulation, using a hybrid granular dynamics-computational fluid
      dynamics model. We find both the bronze-on-top and the sandwich configurations as
      observed in previous experiments. The simulations allow us to give a detailed
      explanation of the phenomena. The key observation is the precise timing of the
      decompaction of the bed with the oscillating gas flow, which will cause the
      bronze to move to the top, due to the difference in acceleration from the air
      drag. For higher frequencies, the different inertia in collisions will cause the
      bronze clusters on top to sink through the bed, leading to a sandwich formation.

PMID- 16907045
TI  - Distribution of local fluxes in diluted porous media.
AB  - We study the distributions of channel openings, local fluxes, and velocities in a
      two-dimensional random medium of nonoverlapping disks. We present theoretical
      arguments supported by numerical data of high precision and find scaling laws as
      functions of the porosity. For the channel openings we observe a crossover to a
      highly correlated regime at small porosities. The distribution of velocities
      through these channels scales with the square of the porosity. The fluxes turn
      out to be the convolution of velocity and channel width corrected by a
      geometrical factor. Furthermore, while the distribution of velocities follows a
      Gaussian form, the fluxes are distributed according to a stretched exponential
      with exponent 1/2. Finally, our scaling analysis allows us to express the
      tortuosity and pore shape factors from the Kozeny-Carman equation as direct
      average properties from microscopic quantities related to the geometry as well as
      the flow through the disordered porous medium.

PMID- 16907046
TI  - Screening in Yukawa fluid mixtures.
AB  - The effective pair potential between mesoscopic charged particles in a
      neutralizing background medium takes a Yukawa form exp(-lambda r)/r with
      screening length lambda(-1). We consider a dilute suspension of such Yukawa
      particles dispersed in a solvent with correlation length xi<lambda(-1) and show
      that the Yukawa interaction is screened if the pair potentials between solvent
      particles exhibit Yukawa decay with the same screening length lambda(-1).
      However, if the solvent pair potentials are shorter ranged than the solute Yukawa
      potentials, then the effective potential between pairs of solute particles is
      unscreened, i.e., the effective potential between the solute particles is equal
      to the bare potential at large particle separations.

PMID- 16907047
TI  - Columnar and lamellar phases in attractive colloidal systems.
AB  - In colloidal suspensions, at low volume fraction and temperature, dynamical
      arrest occurs via the growth of elongated structures that aggregate to form a
      connected network at gelation. Here we show that, in the region of parameter
      space where gelation occurs, the stable thermodynamical phase is a crystalline
      columnar one. Near and above the gelation threshold, the disordered spanning
      network slowly evolves and finally orders to form the crystalline structure. At
      higher volume fractions the stable phase is a lamellar one, which seems to have a
      still longer ordering time.

PMID- 16907048
TI  - Lack of long-range order in confined two-dimensional model colloidal crystals.
AB  - We investigate the nature of the ordered phase for a model of colloidal particles
      confined within a quasi-one-dimensional (Q1D) strip between two parallel
      boundaries, or walls, separated a distance D in two dimensions (2D). Using Monte
      Carlo simulations we find that at densities typical of the bulk 2D triangular
      solid the order in the D1D strip is determined by the nature of the boundaries.
      While the order is enhanced for a suitably corrugated boundary potential, for a
      uniformly repulsive smooth boundary potential ordering normal to the walls is
      enhanced ("layering"), but destroyed parallel to the wall.

PMID- 16907049
TI  - Possible explanation of the Lambda-shape anomaly in polymer surface diffusion.
AB  - We suggest an explanation for the anomalous behavior of the polymer surface
      diffusion coefficient D reported by Zhao and Granick [J. Am. Chem. Soc. 126, 6242
      (2004)]: D first increased with increasing polymer surface concentration Gamma,
      then suddenly dropped at a threshold value Gamma*. Our molecular dynamics
      simulations show the same behavior. We find that polymers form single-layered
      pancake structures for Gamma<Gamma*, while double layers form for Gamma>Gamma*.
      The double-layer structures allow the polymers to better adapt to the substrate
      corrugation. This increases barriers for lateral diffusion and is thus consistent
      with small values of D at larger Gamma.

PMID- 16907050
TI  - Observation of a low-viscosity interface between immiscible polymer layers.
AB  - X-ray photon correlation spectroscopy was employed in a surface standing wave
      geometry in order to resolve the thermally driven in-plane dynamics at both the
      surface/vacuum (top) and polymer/polymer (bottom) interfaces of a thin
      polystyrene (PS) film on top of Poly(4-bromo styrene) (PBrS) and supported on a
      Si substrate. The top vacuum interface shows two relaxation modes: one fast and
      one slow, while the buried polymer-polymer interface shows a single slow mode.
      The slow mode of the top interface is similar in magnitude and wave vector
      dependence to the single mode of the buried interface. The dynamics are
      consistent with a low-viscosity mixed layer between the PS and PBrS and coupling
      of the capillary wave fluctuations between this layer and the PS.

PMID- 16907051
TI  - Density functional theory for flexible and semiflexible polymers of infinite
      length.
AB  - We develop a density functional theory for infinitely long flexible and
      semiflexible polymers, as an appropriate simplification of the corresponding
      treatment of finite chains. We demonstrate that very long chains sometimes are
      required to reproduce even qualitatively correct limiting behaviors.

PMID- 16907052
TI  - Dynamic buckling of morphoelastic filaments.
AB  - The equilibrium shapes of biological structures as diverse as plant tendrils and
      bacterial filaments can be altered by externally imposed stresses of sufficient
      duration. We study the simplest model for this morphoelasticity--a filament whose
      intrinsic curvatures relax to the local curvatures--and illustrate its properties
      in the context of dynamic Euler buckling and writhing. When a thrust or twist is
      ramped in time the effective elastic properties of the filament depend on the
      load rate. Slow ramps interrupted by removal of the external forces can leave in
      equilibrium any of a whole continuum of buckled shapes. Morphoelastic relaxation
      can also allow a filament to bypass a bifurcation.

PMID- 16907053
TI  - Generalized Haldane equation and fluctuation theorem in the steady-state cycle
      kinetics of single enzymes.
AB  - Enzyme kinetics are cyclic. We study a Markov renewal process model of single
      enzyme turnover in nonequilibrium steady state (NESS) with sustained
      concentrations for substrates and products. We show that the forward and backward
      cycle times have identical nonexponential distributions: Theta + (t)=Theta_(t).
      This equation generalizes the Haldane relation in reversible enzyme kinetics. In
      terms of the probabilities for the forward (p+) and backward (p-) cycles, kBT
      ln(p+/p-) is shown to be the chemical driving force of the NESS, Delta mu. More
      interestingly, the moment generating function of the stochastic number of
      substrate cycle v(t), <e-lambda v(t)> , follows the fluctuation theorem in the
      form of Kurchan-Lebowitz-Spohn-type symmetry. When lambda=delta mu/kBT, we obtain
      the Jarzynski-Hatano-Sasa-type equality <e-v(t)Delta mu/kBT> identical with 1 for
      all t, where v Delta mu is the fluctuating chemical work done for sustaining the
      NESS. This theory suggests possible methods to experimentally determine the
      nonequilibrium driving force in situ from turnover data via single-molecule
      enzymology.

PMID- 16907054
TI  - Characteristic length scale of electric transport properties of genomes.
AB  - A tight-binding model together with a statistical method are used to investigate
      the relation between the sequence-dependent electric transport properties and the
      sequences of protein-coding regions of complete genomes. A correlation parameter
      Omega is defined to analyze the relation. For some particular propagation length
      w max, the transport behaviors of the coding and noncoding sequences are very
      different and the correlation reaches its maximal value Omega max. w max and
      Omega max are characteristic values for each species. A possible reason for the
      difference between the features of transport properties in the coding and
      noncoding regions is the mechanism of DNA damage repair processes together with
      natural selection.

PMID- 16907055
TI  - Freezing transition of the directed polymer in a 1 + d random medium: location of
      the critical temperature and unusual critical properties.
AB  - In dimension d > or =3, the directed polymer in a random medium undergoes a phase
      transition between a free phase at high temperature and a low-temperature
      disorder-dominated phase. For the latter phase, Fisher and Huse have proposed a
      droplet theory based on the scaling of the free-energy fluctuations Delta F(l)
      approximately l theta at scale l. On the other hand, in related growth models
      belonging to the Kardar-Parisi-Zhang universality class, Forrest and Tang have
      found that the height-height correlation function is logarithmic at the
      transition. For the directed polymer model at criticality, this translates into
      logarithmic free-energy fluctuations Delta FTc(l) approximately (lnl)sigma with
      sigma = 1/2. In this paper, we propose a droplet scaling analysis exactly at
      criticality based on this logarithmic scaling. Our main conclusion is that the
      typical correlation length xi(T) of the low-temperature phase diverges as ln
      xi(t) approximately [-ln(Tc-T)]1/sigma approximately [-ln(Tc-T)]2, instead of the
      usual power law xi(T) approximately (Tc-T)-v. Furthermore, the logarithmic
      dependence of Delta FTc(l) leads to the conclusion that the critical temperature
      Tc actually coincides with the explicit upper bound T2 derived by Derrida and co
      workers, where T2 corresponds to the temperature below which the ratio Z 2
      L/(ZL)2 diverges exponentially in L. Finally, since the Fisher-Huse droplet
      theory was initially introduced for the spin-glass phase, we briefly mention the
      similarities with and differences from the directed polymer model. If one
      speculates that the free energy of droplet excitations for spin glasses is also
      logarithmic at Tc, one obtains a logarithmic decay for the mean square
      correlation function at criticality, C2(r) approximately 1/(ln r)sigma, instead
      of the usual power law l/rd-2+eta.

PMID- 16907056
TI  - Logarithmic corrections in the free energy of monomer-dimer model on plane
      lattices with free boundaries.
AB  - Using exact computations we study the classical hard-core monomer-dimer models on
      m x n plane lattice strips with free boundaries. For an arbitrary number v of
      monomers (or vacancies), we found a logarithmic correction term in the finite
      size correction of the free energy per lattice site. The coefficient of the
      logarithmic correction term depends on the number of monomers present (v) and the
      parity of the width n of the lattice strip: the coefficient equals to v when n is
      odd, and v/2 when n is even. The results are generalizations of the previous
      results for a single monomer in an otherwise fully packed lattice of dimers. We
      also study the finite-size correction in the low dimer density limit, where the
      number of dimers d is fixed. In this case the coefficient of the logarithmic
      correction term equals to d, for both odd and even n.

PMID- 16907057
TI  - Sol-gel transition in a source-enhanced coagulating system.
AB  - This paper considers the time evolution of disperse systems in which binary
      coagulation and a source of fresh particles govern the temporal changes to the
      particle mass spectra. The source is assumed to produce fresh particles at a
      constant rate. The Smoluchowski equation describing the time evolution of the
      particle mass spectrum is solved exactly for the coagulation kernel proportional
      to the product of masses of two coalescing particles. It is shown that after a
      critical time tc a gel forms in the system and the sol spectrum becomes an
      algebraic function of the particle mass at t=tc. It begins to shrink after the
      critical time due to the mass loss supporting the growth of the gel mass. The pre
      and post-critical behavior of the mass spectrum and its integral characteristics
      (total particle number and mass concentrations) are investigated for the source
      productivity I(g) dropping down algebraically with the particle mass g as I(g)
      proportional variant g -gamma. The critical particle mass spectrum is proved to
      be a universal function of (it drops down as g -5/2) if the third moment of I(g)
      is finite (gamma>4). Otherwise (3<gamma< or =4)this and other critical exponents
      begin to depend on . Still the mass spectrum remains self-similar, i.e., it
      depends on a combination of g and t. At smaller gamma the gelation process is
      shown to begin at t=0. All critical characteristics of the particle mass spectrum
      are determined for this case.

PMID- 16907058
TI  - Global phase diagram and six-state clock universality behavior in the triangular
      antiferromagnetic Ising model with anisotropic next-nearest-neighbor coupling:
      level-spectroscopy approach.
AB  - We investigate the triangular-lattice antiferromagnetic Ising model with a
      spatially anisotropic next-nearest-neighbor ferromagnetic coupling, which was
      first discussed by Kitatani and Oguchi. By employing the effective geometric
      factor, we analyze the scaling dimensions of the operators around the Berezinskii
      Kosterlitz-Thouless (BKT) transition lines, and determine the global phase
      diagram. Our numerical data exhibit that two types of BKT-transition lines
      separate the intermediate critical region from the ordered and disordered phases,
      and they do not merge into a single curve in the antiferromagnetic region. We
      also estimate the central charge and perform some consistency checks among
      scaling dimensions in order to provide the evidence of the six-state clock
      universality. Further, we provide an analysis of the shapes of boundaries based
      on the crossover argument.

PMID- 16907059
TI  - Fractional translational diffusion of a Brownian particle in a double well
      potential.
AB  - The fractional translational diffusion of a particle in a double-well potential
      (excluding inertial effects) is considered. The position correlation function and
      its spectrum are evaluated using a fractional probability density diffusion
      equation (based on the diffusion limit of a fractal time random walk). Exact and
      approximate solutions for the dynamic susceptibility describing the position
      response to a small external field are obtained. The exact solution is given by
      matrix continued fractions while the approximate solution relies on the
      exponential separation of the time scales of the fast "intrawell" and low
      overbarrier relaxation processes associated with the bistable potential. It is
      shown that knowledge of the characteristic relaxation times for normal diffusion
      allows one to predict accurately the anomalous relaxation behavior of the system
      for all relevant time scales.

PMID- 16907060
TI  - Phase transitions in systems possessing shock solutions.
AB  - Recently it has been shown that there are three families of stochastic one
      dimensional nonequilibrium lattice models for which the single-shock measures
      form an invariant subspace of the states of these models. Here, both the
      stationary states and dynamics of single-shocks on a one-dimensional lattice are
      studied. This is done for both an infinite lattice and a finite lattice with
      boundaries. It is seen that these models possess both static and dynamical phase
      transitions. The static phase transition is the well-known low-high density phase
      transition for the asymmetric simple exclusion process. The branching-coalescing
      random walk and asymmetric Kawasaki-Glauber process models also show the same
      phase transition. Double-shocks on a one-dimensional lattice are also
      investigated. It is shown that at the stationary state the contribution of double
      shocks with higher width becomes small, and the main contribution comes from thin
      double-shocks.

PMID- 16907061
TI  - Continuous phase transitions with a convex dip in the microcanonical entropy.
AB  - The appearance of a convex dip in the microcanonical entropy of finite systems
      usually signals a first order transition. However, a convex dip also shows up in
      some systems with a continuous transition as, for example, in the Baxter-Wu model
      and in the four-state Potts model in two dimensions. We demonstrate that the
      appearance of a convex dip in those cases can be traced back to a finite-size
      effect. The properties of the dip are markedly different from those associated
      with a first order transition and can be understood within a microcanonical
      finite-size scaling theory for continuous phase transitions. Results obtained
      from numerical simulations corroborate the predictions of the scaling theory.

PMID- 16907062
TI  - Velocity and diffusion coefficient of A + A <--> A reaction fronts in one
      dimension.
AB  - We study front propagation in the reversible reaction-diffusion system A + A <-->
      A on a one-dimensional lattice. Extending the idea of leading particle in
      studying the motion of the front we write a master equation in the stochastically
      moving frame attached to this particle. This approach provides a systematic way
      to improve on estimates of front speed obtained earlier. We also find that the
      leading particle performs a correlated random walk and this correlation needs to
      be taken into account to get the correct the value of the front diffusion
      coefficient.

PMID- 16907063
TI  - Dynamic phase transition in the kinetic spin- Blume-Capel model under a time
      dependent oscillating external field.
AB  - We present a study, within a mean-field approach, of the stationary states of the
      kinetic spin-3/2 Blume-Capel model in the presence of a time-dependent
      oscillating external magnetic field. We use the Glauber-type stochastic dynamics
      to describe the time evolution of the system. We have found that the behavior of
      the system strongly depends on the crystal-field interaction. We can identify two
      types of solutions: a symmetric one where the magnetization (m) of the system
      oscillates in time around zero, which corresponds to a paramagnetic phase (P),
      and an antisymmetric one where m oscillates in time around a finite value
      different from zero, namely +/-3/2 and +/-1/2 that corresponds to the
      ferromagnetic-3/2 (F3/2) and the ferromagnetic-1/2 (F1/2) phases, respectively.
      There are coexistence regions of the phase space where the F3/2, F1/2, (F3/2 +
      F1/2), F3/2, P(F3/2 + P), F1/2, and P(F1/2 + P), F3/2, F1/2, P(F3/2 + F1/2 + P)
      phases coexist, hence the system exhibits seven different phases. We obtain the
      dynamic phase transition points and find six fundamental phase diagrams which
      exhibit one or three dynamic tricritical points. We have also calculated the
      Liapunov exponent to verify the stability of the solutions and the dynamic phase
      transition points.

PMID- 16907064
TI  - Generic multifractality in exponentials of long memory processes.
AB  - We find that multifractal scaling is a robust property of a large class of
      continuous stochastic processes, constructed as exponentials of long-memory
      processes. The long memory is characterized by a power law kernel with tail
      exponent phi+1/2, where phi>0. This generalizes previous studies performed only
      with phi=0(with a truncation at an integral scale) by showing that
      multifractality holds over a remarkably large range of dimensionless scales for
      phi>0. The intermittency multifractal coefficient can be tuned continuously as a
      function of the deviation phi from 1/2 and of another parameter sigma2 embodying
      information on the short-range amplitude of the memory kernel, the ultraviolet
      cutoff ("viscous") scale, and the variance of the white-noise innovations. In
      these processes, both a viscous scale and an integral scale naturally appear,
      bracketing the "inertial" scaling regime. We exhibit a surprisingly good collapse
      of the multifractal spectra zeta(q) on a universal scaling function, which
      enables us to derive high-order multifractal exponents from the small-order
      values and also obtain a given multifractal spectrum zeta(q) by different
      combinations of phi and sigma2.

PMID- 16907065
TI  - Dynamics of the Bose-Einstein condensation: analogy with the collapse dynamics of
      a classical self-gravitating Brownian gas.
AB  - We consider the dynamics of a gas of free bosons within a semiclassical Fokker
      Planck equation for which we give a physical justification. In this context, we
      find a striking similarity between the Bose-Einstein condensation in the
      canonical ensemble, and the gravitational collapse of a gas of classical self
      gravitating Brownian particles. The paper is mainly devoted to the complete study
      of the Bose-Einstein "collapse" within this model. We find that at the Bose
      Einstein condensation temperature Tc, the chemical potential mu(t) vanishes
      exponentially with a universal rate that we compute exactly. Below Tc, we show
      analytically that square root mu(t) vanishes linearly in a finite time t coll.
      After t coll, the mass of the condensate grows linearly with time and saturates
      exponentially to its equilibrium value for large time. We also give analytical
      results for the density scaling functions, for the corrections to scaling, and
      for the exponential relaxation time. Finally, we find that the equilibration time
      (above Tc) and the collapse time T coll(below Tc) both behave like -T -3 c ln|T
      Tc|, near Tc.

PMID- 16907066
TI  - Nonequilibrium thermodynamics of glasses.
AB  - We consider the nonequilibrium thermodynamics of glasses from various
      perspectives. For the commonly used equilibriumlike approach based on Gibbs'
      fundamental form with an additional pair of conjugate variables, we discuss
      possible choices of the independent out-of-equilibrium variable and we illustrate
      some implications by concrete results for a well-known exactly solvable lattice
      model. The choice of variables is further illuminated from the complementary
      atomistic perspective offered by the inherent-structure formalism. A general
      formalism of nonequilibrium thermodynamics is employed (i) to derive the standard
      equilibriumlike approach, (ii) to formulate two self-contained levels to describe
      glassy dynamics and thermodynamics, and (iii) to offer guidance for future
      simulations of glasses. The thermodynamic approach suggests to introduce four
      point correlation functions associated with structural rearrangements after
      imposed deformations, which might offer a possibility to detect a growing length
      scale at the glass transition without employing any dynamic information.

PMID- 16907067
TI  - Chaotic noisy transport of electron pairs in a superconducting junction device:
      thermal-inertia ratchets.
AB  - Chaotic noisy transport of electron pairs in a superconducting junction device
      (thermal-inertia ratchets) is investigated. The study shows that when the
      temperature is low enough, the transport of the electron pairs can be mainly
      chaotic; when the temperature is high enough, it can be mainly stochastic. By
      controlling the temperature and the amplitude of the input ac signal, the current
      of electron pairs can be reversed.

PMID- 16907068
TI  - Exactly solvable interacting spin-ice vertex model.
AB  - A special family of solvable five-vertex model is introduced on a square lattice.
      In addition to the usual nearest-neighbor interactions, the vertices defining the
      model also interact along one of the diagonals of the lattice. This family of
      models includes in a special limit the standard six-vertex model. The exact
      solution of these models is an application of the matrix product ansatz
      introduced recently and applied successfully in the solution of quantum chains.
      The phase diagram and the free energy of the models are calculated in the
      thermodynamic limit. The models exhibit massless phases, and our analytical and
      numerical analyses indicate that such phases are governed by a conformal field
      theory with central charge c=1 and continuously varying critical exponents.

PMID- 16907069
TI  - Bulk and surface transitions in asymmetric simple exclusion process: impact on
      boundary layers.
AB  - In this paper, we study the boundary-induced phase transitions in a particle
      nonconserving asymmetric simple exclusion process with open boundaries. Using a
      boundary layer analysis on the mean field version of the model, we show that the
      key signatures of various bulk phase transitions are present in the boundary
      layers of the density profiles. In addition, we also find surface transitions in
      the low- and high-density phases. The surface transition in the low-density phase
      provides a complete description of the nonequilibrium critical point found in
      this system.

PMID- 16907070
TI  - Generic features of the wealth distribution in ideal-gas-like markets.
AB  - We provide an exact solution to the ideal-gas-like models studied in econophysics
      to understand the microscopic origin of Pareto law. In these classes of models
      the key ingredient necessary for having a self-organized scale-free steady-state
      distribution is the trading or collision rule where agents or particles save a
      definite fraction of their wealth or energy and invest the rest for trading.
      Using a Gibbs ensemble approach we could obtain the exact distribution of wealth
      in this model. Moreover we show that in this model (a) good savers are always
      rich and (b) every agent poor or rich invests the same amount for trading.
      Nonlinear trading rules could alter the generic scenario observed here.

PMID- 16907071
TI  - Transport coefficients of a quantum system interacting with a squeezed heat bath.
AB  - The analytical expressions for the time-dependent friction and diffusion
      coefficients are presented for the case of coupling in coordinates between the
      collective subsystem and a squeezed heat bath. The effects of initial phase
      sensitive and -insensitive correlations of the heat bath on the diffusion
      coefficients, fluctuations, and decoherence are studied. The interplay between
      friction and decoherence is discussed.

PMID- 16907072
TI  - Density of Yang-Lee zeros for the Ising ferromagnet.
AB  - The densities of Yang-Lee zeros for the Ising ferromagnet on the L x L square
      lattice are evaluated from the exact grand partition functions (L=3 approximately
      16). The properties of the density of Yang-Lee zeros are discussed as a function
      of temperature T and system size L. The three different classes of phase
      transitions for the Ising ferromagnet--first-order phase transition, second-order
      phase transition, and Yang-Lee edge singularity--are clearly distinguished by
      estimating the magnetic scaling exponent yh from the densities of zeros for
      finite-size systems. The divergence of the density of zeros at Yang-Lee edge in
      high temperatures (Yang-Lee edge singularity), which has been detected only by
      the series expansion until now for the square-lattice Ising ferromagnet, is
      obtained from the finite-size data. The identification of the orders of phase
      transitions in small systems is also discussed using the density of Yang-Lee
      zeros.

PMID- 16907073
TI  - Nonanalytic microscopic phase transitions and temperature oscillations in the
      microcanonical ensemble: an exactly solvable one-dimensional model for
      evaporation.
AB  - We calculate exactly both the microcanonical and canonical thermodynamic
      functions (TDFs) for a one-dimensional model system with piecewise constant
      Lennard-Jones type pair interactions. In the case of an isolated N-particle
      system, the microcanonical TDFs exhibit (N - 1) singular (nonanalytic)
      microscopic phase transitions of the formal order N/2, separating N energetically
      different evaporation (dissociation) states. In a suitably designed evaporation
      experiment, these types of phase transitions should manifest themselves in the
      form of pressure and temperature oscillations, indicating cooling by evaporation.
      In the presence of a heat bath (thermostat), such oscillations are absent, but
      the canonical heat capacity shows a characteristic peak, indicating the
      temperature-induced dissociation of the one-dimensional chain. The distribution
      of complex zeros of the canonical partition may be used to identify different
      degrees of dissociation in the canonical ensemble.

PMID- 16907074
TI  - Kardar-Parisi-Zhang interfaces bounded by long-ranged potentials.
AB  - We study unbinding transitions of a nonequilibrium Kardar-Parisi-Zhang interface
      in the presence of long-ranged substrates. Both attractive and repulsive
      substrates, as well as positive and negative Kardar-Parisi-Zhang nonlinearities,
      are considered, leading to four different physical situations. A detailed
      comparison with equilibrium wetting transitions as well as with nonequilibrium
      unbinding transitions in systems with short-ranged forces is presented, yielding
      a comprehensive picture of unbinding transitions and of their classification into
      universality classes. These nonequilibrium transitions may play a crucial role in
      the dynamics of the wetting or growth of systems with intrinsic anisotropies.

PMID- 16907075
TI  - Ising model on two connected Barabasi-Albert networks.
AB  - We investigate analytically the behavior of the Ising model on two connected
      Barabasi-Albert networks. Depending on relative ordering of both networks there
      are two possible phases corresponding to parallel or antiparallel alignment of
      spins in both networks. A difference between critical temperatures of both phases
      disappears in the limit of vanishing inter-network coupling for identical
      networks. The analytic predictions are confirmed by numerical simulations.

PMID- 16907076
TI  - Directed percolation with incubation times.
AB  - We introduce a model for directed percolation with a long-range temporal
      diffusion, while the spatial diffusion is kept short ranged. In an interpretation
      of directed percolation as an epidemic process, this non-Markovian modification
      can be understood as incubation times, which are distributed accordingly to a
      Levy distribution. We argue that the best approach to find the effective action
      for this problem is through a generalization of the Cardy-Sugar method, adding
      the non-Markovian features into the geometrical properties of the lattice. We
      formulate a field theory for this problem and renormalize it up to one loop in a
      perturbative expansion. We solve the various technical difficulties that the
      integrations possess by means of an asymptotic analysis of the divergences. We
      show the absence of field renormalization at one-loop order, and we argue that
      this would be the case to all orders in perturbation theory. Consequently, in
      addition to the characteristic scaling relations of directed percolation, we find
      a scaling relation valid for the critical exponents of this theory. In this
      universality class, the critical exponents vary continuously with the Levy
      parameter.

PMID- 16907077
TI  - Moment ratios for the pair-contact process with diffusion.
AB  - We study the continuous absorbing-state phase transition in the one-dimensional
      pair contact process with diffusion (PCPD). In previous studies [Dickman and de
      Menezes, Phys. Rev. E 66, 045101(R) (2002)], the critical point moment ratios of
      the order parameter showed anomalous behavior, growing with system size rather
      than taking universal values, as expected. Using the quasistationary simulation
      method we determine the moments of the order parameter up to fourth order at the
      critical point, in systems of up to 40,960 sites. Due to strong finite-size
      effects, the ratios converge only for large system sizes. Moment ratios and
      associated order-parameter histograms are compared with those of directed
      percolation. We also report an improved estimate [pc=0.077092(1)] for the
      location of the critical point in the nondiffusive pair contact process.

PMID- 16907078
TI  - Phase transitions and superuniversality in the dynamics of a self-driven
      particle.
AB  - We study an active random walker model in which a particle's motion is determined
      by a self-generated field. The field encodes information about the particle's
      path history. This leads to either self-attractive or self-repelling behavior.
      For self-repelling behavior, we find a phase transition in the dynamics: when the
      coupling between the field and the walker exceeds a critical value, the
      particle's behavior changes from renormalized diffusion to one characterized by a
      diverging diffusion coefficient. The dynamical behavior for all cases is
      surprisingly independent of dimension and of the noise amplitude.

PMID- 16907079
TI  - Upper and lower bounds of stochastic resonance and noise-induced synchronization
      in a bistable oscillator.
AB  - This paper discusses concepts of stochastic resonance and noise-induced
      synchronization in a bistable oscillator subject to both periodic signal and
      noise. We demonstrate that stochastic resonance is not directly correlated with
      the matching of the signal frequency and the switching rate. The phenomena of
      stochastic resonance and noise-induced synchronization are the limiting cases of
      noise-induced transitions, and the spectral response heavily depends on the input
      signal-to-noise ratio. The lower and upper bounds of noise intensity allowing
      synchronization are found as functions of the system's parameters.

PMID- 16907080
TI  - Monte Carlo results for continuum percolation in low and high dimensions.
AB  - We report on Monte Carlo simulations of continuum percolation thresholds, by
      implementing highly efficient algorithms for very large samples. Our work, which
      includes percolation of hyperspheres, hypercubes, and boxes, in various
      dimensions, sizes, and shapes, has confirmed the expected dependence of the
      threshold on Vex, the total excluded volume, and on Bc, the average number of
      bonds per site. We have further confirmed that Vex=Bc, and that Bc is dependent
      on the objects shape, for which we offer a possible explanation. In particular we
      find that, counterintuitively, one can have Bc<1, as we have found for
      hyperspheres of dimension > or =12. From our many results for differently sized
      hyperspheres, we were also able to derive the correlation length exponent v
      solely from the behavior of the thresholds using finite-size scaling.

PMID- 16907081
TI  - Bridge functions near the liquid-vapor coexistence curve in binary Lennard-Jones
      mixtures.
AB  - We have carried out extensive molecular-dynamics simulation studies of binary
      Lennard-Jones mixtures to calculate directly the bridge function at state points
      lying in a very narrow single fluid phase region between the vapor-liquid and
      solid-liquid coexistence lines [Lamm and Hall, Fluid Phase Equilib. 182, 37
      (2001); 194-197, 197 (2002)]. By varying the density close to the liquid-vapor
      coexistence line, significant deviations are observed at intermediate distances
      between the simulated bridge function and two widely used approximate closures in
      the integral equation theory of liquids, viz. the hybrid mean spherical
      approximation and the Duh-Henderson closures. The overall qualitative agreement
      remains the same with small variation in temperature that brings the system
      closer to either the liquid-vapor or liquid-solid coexistence curve. We also
      report a comparison of the direct and indirect correlation functions obtained
      from our simulation studies as well as from the integral equation theory of
      liquids. Our results emphasize the need for developing new closures applicable to
      binary fluid mixtures over a wide range of thermodynamic parameters.

PMID- 16907082
TI  - Long-time behavior of the velocity autocorrelation function at low densities and
      near the critical point of simple fluids.
AB  - Numerous theoretical and numerical works have been devoted to the study of the
      algebraic decrease at large times of the velocity autocorrelation function of
      particles in a fluid. The derivation of this behavior, the so-called long-time
      tail, generally based on linearized hydrodynamics, makes no reference to any
      specific characteristic of the particle interactions. However, in the literature
      doubts have been expressed about the possibility that by numerical simulations
      the long-time tail can be observed in the whole fluid phase domain of systems in
      which the particles interact by soft-core and attractive pair potentials. In this
      work, extensive and accurate molecular-dynamics simulations establish that the
      predicted long-time tail of the velocity autocorrelation function exists in a low
      density fluid of particles interacting by a soft-repulsive potential and near the
      liquid-gas critical point of a Lennard-Jones system. These results contribute to
      the confirmation that the algebraic decay of the velocity autocorrelation
      function is universal in these fluid systems.

PMID- 16907083
TI  - Pattern formation during air injection into granular materials confined in a
      circular Hele-Shaw cell.
AB  - We investigate the dynamics of granular materials confined in a radial Hele-Shaw
      cell, during central air injection. The behavior of this granular system, driven
      by its interstitial fluid, is studied both experimentally and numerically. This
      allows us to explore the associated pattern formation process, characterize its
      features and dynamics. We classify different hydrodynamic regimes as function of
      the injection pressure. The numerical model takes into account the interactions
      between the granular material and the interstitial fluid, as well as the solid
      solid interactions between the grains and the confining plates. Numerical and
      experimental results are comparable, both to reproduce the hydrodynamical regimes
      experimentally observed, as well as the dynamical features associated to
      fingering and compacting.

PMID- 16907084
TI  - Statistical description of sediment transport experiments.
AB  - A longstanding problem in the study of sediment transport in gravel-bed rivers is
      related to the physical mechanisms governing bed resistance and particle motion.
      To study this problem, we investigated the motion of coarse spherical glass beads
      entrained by a steady shallow turbulent water flow down a steep two-dimensional
      channel with a mobile bed. This experimental facility is the simplest
      representation of sediment transport on the laboratory scale, with the tremendous
      advantages that boundary conditions are perfectly controlled and a wealth of
      information can be obtained using imaging techniques. Flows were filmed from the
      side by a high-speed camera. Using image processing software made it possible to
      determine the flow characteristics such as particle trajectories, their state of
      motion (rest, rolling, or saltating motion), and flow depth. In accordance with
      earlier investigations, we observed that over short time periods, sediment
      transport appeared as a very intermittent process. To interpret these results, we
      revisited Einstein's theory on sediment and derived the statistical properties
      (probability distribution and autocorrelation function) of the key variables such
      as the solid discharge and the number of moving particles. Analyzing the
      autocorrelation functions and the probability distributions of our measurements
      revealed the existence of long-range correlations. For instance, whereas theory
      predicts a Binomial distribution for the number of moving particles, experiments
      demonstrated that a negative binomial distribution best fit our data, which
      emphasized the crucial role played by wide fluctuations. These frequent wide
      fluctuations stemmed particle entrainment and motion being collective phenomena
      rather than individual processes, contrary to what is assumed in most theoretical
      models.

PMID- 16907085
TI  - Front propagation sustained by additive noise.
AB  - The effect of noise in a motionless front between a periodic spatial state and an
      homogeneous one is studied. Numerical simulations show that noise induces front
      propagation. From the subcritical Swift-Hohenberg equation with noise, we deduce
      an adequate equation for the envelope and the core of the front. The equation of
      the core of the front is characterized by an asymmetrical periodic potential plus
      additive noise. The conversion of random fluctuations into direct motion of the
      core of the front is responsible of the propagation. We obtain an analytical
      expression for the velocity of the front, which is in good agreement with
      numerical simulations.

PMID- 16907087
TI  - Collapse of periodic orbits in a driven inelastic particle system.
AB  - The dynamical behavior of a one-dimensional inelastic particle system with
      particles of unequal mass traveling between two walls is investigated. The system
      is driven by adding energy at one of the walls while the other wall is stationary
      and does not add energy. By deriving analytic solutions for the periodic orbits
      of this system, we show that there are a countable infinity of critical mass
      ratios at which the particle dynamics become highly degenerate in the following
      sense. As the mass ratio passes through these critical points, large numbers of
      stable periodic orbits can collapse onto a single trivial orbit. We show that the
      widely studied equal-mass systems represent one of these critical points and are
      therefore such a degenerate case. We also show that in the elastic limit the
      number of orbits that collapse onto the single trivial orbit can become
      arbitrarily large.

PMID- 16907086
TI  - Fluidization of a vertically vibrated two-dimensional hard sphere packing: a
      granular meltdown.
AB  - We report measurements of the fluidization process in vertically vibrated two
      dimensional granular packings. An initially close packed granular bed is exposed
      to sinusoidal container oscillations with gradually increasing amplitude. At
      first the particles close to the free surface become mobile. When a critical
      value of the forcing strength is reached the remaining crystal suddenly breaks up
      and the bed fluidizes completely. This transition leads to discontinuous changes
      in the density distribution and in the root mean square displacement of the
      individual particles. Likewise the vertical center of mass coordinate increases
      by leaps and bounds at the transition. It turns out that the maximum container
      velocity v0 is the crucial driving parameter determining the state of a fully
      fluidized system. For particles of various sizes the transition to full
      fluidization occurs at the same value of v 2 0/gd, where d is the particle
      diameter and g is the gravitational acceleration. A discontinuous fluidization
      transition is only observed when the particles are highly elastic.

PMID- 16907088
TI  - Flux through a hole from a shaken granular medium.
AB  - We have measured the flux of grains from a hole in the bottom of a shaken
      container of grains. We find that the peak velocity of the vibration, v max,
      controls the flux, i.e., the flux is nearly independent of the frequency and
      acceleration amplitude for a given value of v max. The flux decreases with
      increasing peak velocity and then becomes almost constant for the largest values
      of v max. The data at low peak velocity can be quantitatively described by a
      simple model, but the crossover to nearly constant flux at larger peak velocity
      suggests a regime in which the granular density near the container bottom is
      independent of the energy input to the system.

PMID- 16907089
TI  - Mechanisms in the size segregation of a binary granular mixture.
AB  - A granular mixture of particles of two sizes that is shaken vertically will in
      most cases segregate. If the larger particles accumulate at the top of the
      sample, this is called the Brazil-nut effect (BNE); if they accumulate at the
      bottom, it is called the reverse Brazil-nut effect (RBNE). While this process is
      of great industrial importance in the handling of bulk solids, it is not well
      understood. In recent years ten different mechanisms have been suggested to
      explain when each type of segregation is observed. However, the dependence of the
      mechanisms on driving conditions and material parameters and hence their relative
      importance is largely unknown. In this paper we present experiments and
      simulations where both types of particles are made from the same material and
      shaken under low air pressure, which reduces the number of mechanisms to be
      considered to seven. We observe both BNE and RBNE by varying systematically the
      driving frequency and amplitude, diameter ratio, ratio of total volume of small
      to large particles, and overall sample volume. All our results can be explained
      by a combination of three mechanisms: a geometrical mechanism called void
      filling, transport of particles in sidewall-driven convection rolls, and thermal
      diffusion, a mechanism predicted by kinetic theory.

PMID- 16907090
TI  - Relaxation of jammed colloidal suspensions after shear cessation.
AB  - The dynamics of heterogeneities in a shear thickening, concentrated colloidal
      suspension is investigated through speckle visibility spectroscopy, a dynamic
      light scattering technique recently introduced [P. K. Dixon and D. J. Durian,
      Phys. Rev. Lett. 90, 184302 (2003)]. Formation of shear-induced heterogeneities
      is observed in the jamming regime, and their relaxation after shear cessation is
      monitored as a function of the applied shear stress. The relaxation time of these
      heterogeneities increases when a higher stress is applied.

PMID- 16907091
TI  - Formalism for calculation of polymer-solvent-mediated potential.
AB  - A simple theoretical approach is proposed for calculation of a solvent-mediated
      potential (SMP) between two colloid particles immersed in a polymer solvent bath
      in which the polymer is modeled as a chain with intramolecular degrees of
      freedom. The present recipe is only concerned with the estimation of the density
      profile of a polymer site around a single solute colloid particle instead of two
      solute colloid particles separated by a varying distance as done in existing
      calculational methods for polymer-SMP. Therefore the present recipe is far
      simpler for numerical implementation than the existing methods. The resultant
      predictions for the polymer-SMP and polymer solvent-mediated mean force (polymer
      SMMF) are in very good agreement with available simulation data. With the present
      recipe, change tendencies of the contact value and second virial coefficiency of
      the SMP as a function of size ratio between the colloid particle and polymer
      site, the number of sites per chain, and the polymer concentration are
      investigated in detail. The metastable critical polymer concentration as a
      function of size ratio and the number of sites per chain is also reported for the
      first time. To yield the numerical solution of the present recipe at less than on
      a personal computer, a rapid and accurate algorithm for the numerical solution of
      the classical density functional theory is proposed to supply rapid and accurate
      estimation of the density profile of the polymer site as an input into the
      present formalism.

PMID- 16907092
TI  - Cooperative behavior and pattern formation in mixtures of driven and nondriven
      colloidal assemblies.
AB  - We simulate a disordered assembly of particles interacting through a repulsive
      Yukawa potential with a small fraction of the particles coupled to an external
      drive. Distortions in the arrangement of the nondriven particles produce a
      dynamically induced effective attraction between the driven particles, giving
      rise to intermittent one-dimensional stringlike structures. The velocity of a
      moving string increases with the number of driven particles in the string. We
      identify the average stable string length as a function of driving force,
      background particle density, and particle charge. This model represents a type of
      collective transport system composed of interacting particles moving through
      deformable disorder.

PMID- 16907093
TI  - Dynamic scaling in entangled mean-field gelation polymers.
AB  - We present a simple reaction kinetics model to describe the polymer synthesis
      used by Lusignan et al. [Phys. Rev. E 60, 5657 (1999)] to produce randomly
      branched polymers in the vulcanization class. Numerical solution of the rate
      equations gives probabilities for different connections in the final product,
      which we use to generate a numerical ensemble of representative molecules. All
      structural quantities probed in the experiments are in quantitative agreement
      with our results for the entire range of molecular weights considered. However,
      with detailed topological information available in our calculations, our estimate
      of the "rheologically relevant" linear segment length is smaller than that
      estimated from the experimental results. We use a numerical method based on a
      tube model of polymer melts to calculate the rheological properties of such
      molecules. Results are in good agreement with experiment, except that in the case
      of the largest molecular weight samples our estimate of the zero-shear viscosity
      is significantly lower than the experimental findings. Using acid concentration
      as an indicator for closeness to the gelation transition, we show that the high
      molecular-weight polymers considered are at the limit of mean-field behavior-
      which possibly is the reason for this disagreement. For a truly mean-field
      gelation class of model polymers, we numerically calculate the rheological
      properties for a range of segment lengths. Our calculations show that the tube
      theory with dynamical dilation predicts that, very close to the gelation limit,
      the contribution to viscosity for this class of polymers is dominated by the
      contribution from constraint-release Rouse motion and the final viscosity
      exponent approaches a Rouse-like value.

PMID- 16907094
TI  - Nonlinear electrochemical relaxation around conductors.
AB  - We analyze the simplest problem of electrochemical relaxation in more than one
      dimension-the response of an uncharged, ideally polarizable metallic sphere (or
      cylinder) in a symmetric, binary electrolyte to a uniform electric field. In
      order to go beyond the circuit approximation for thin double layers, our analysis
      is based on the Poisson-Nernst-Planck (PNP) equations of dilute solution theory.
      Unlike most previous studies, however, we focus on the nonlinear regime, where
      the applied voltage across the conductor is larger than the thermal voltage. In
      such strong electric fields, the classical model predicts that the double layer
      adsorbs enough ions to produce bulk concentration gradients and surface
      conduction. Our analysis begins with a general derivation of surface conservation
      laws in the thin double-layer limit, which provide effective boundary conditions
      on the quasineutral bulk. We solve the resulting nonlinear partial differential
      equations numerically for strong fields and also perform a time-dependent
      asymptotic analysis for weaker fields, where bulk diffusion and surface
      conduction arise as first-order corrections. We also derive various dimensionless
      parameters comparing surface to bulk transport processes, which generalize the
      Bikerman-Dukhin number. Our results have basic relevance for double-layer
      charging dynamics and nonlinear electrokinetics in the ubiquitous PNP
      approximation.

PMID- 16907095
TI  - Dynamics of ternary mixtures with photosensitive chemical reactions: creating
      three-dimensionally ordered blends.
AB  - Using computer simulations, we establish an approach for creating defect-free,
      periodically ordered polymeric materials. The system involves ABC ternary
      mixtures where the A and B components undergo a reversible photochemical
      reaction. In addition, all three components are mutually immiscible and undergo
      phase separation. Through the simulations, we model the effects of illuminating a
      three-dimensional (3D) sample with spatially and temporally dependent light
      irradiation. Experimentally, this situation can be achieved by utilizing both a
      uniform background light and a spatially localized, higher intensity light, and
      then rastering a higher-intensity light over the 3D sample. We first focus on the
      case where the higher-intensity light is held stationary and focused in a
      distinct region within the system. The C component is seen to displace the A and
      B within this region and replicate the pattern formed by the higher-intensity
      light. In effect, one can write a pattern of C onto the AB binary system by
      focusing the higher-intensity light in the desired arrangement. We isolate the
      conditions that are necessary for producing clearly written patterns of C (i.e.,
      for obtaining sharp interfaces between the C and A/B domains). We next consider
      the effect of rastering a higher-intensity light over this sample and find that
      this light "combs out" defects in the AB blend as it moves through the system.
      The resulting material displays a defect-free structure that encompasses both a
      periodic ordering of the A and B domains and a well-defined motif of C. In this
      manner, one can create hierarchically patterned materials that exhibit
      periodicity over two distinct length scales. The approach is fully reversible,
      noninvasive, and points to a novel means of patterning with homopolymers, which
      normally do not self-assemble into periodic structures.

PMID- 16907096
TI  - Cole-Cole law for critical dynamics in glass-forming liquids.
AB  - Within the mode-coupling theory (MCT) for glassy dynamics, the asymptotic low
      frequency expansions for the dynamical susceptibilities at critical points are
      compared to the expansions for the dynamic moduli; this shows that the
      convergence properties of the two expansions can be quite different. In some
      parameter regions, the leading-order expansion formula for the modulus describes
      the solutions of the MCT equations of motion outside the transient regime
      successfully; at the same time, the leading- and next-to-leading-order expansion
      formulas for the susceptibility fail. In these cases, one can derive a Cole-Cole
      law for the susceptibilities; and this law accounts for the dynamics for
      frequencies below the band of microscopic excitations and above the high
      frequency part of the alpha peak. It is shown that this scenario explains the
      optical-Kerr-effect data measured for salol and benzophenone (BZP). For BZP it is
      inferred that the depolarized light-scattering spectra exhibit a wing for the
      alpha peak within the Gigahertz band. This wing results from the crossover of the
      von Schweidler law part of the alpha peak to the high-frequency part of the Cole
      Cole peak; and this crossover can be described quantitatively by the leading
      order formulas of MCT for the modulus.

PMID- 16907097
TI  - Observations of coarsening of air voids in a polymer-highly-soluble crystalline
      matrix during dissolution.
AB  - A combination of magnetic resonance imaging and x-ray microcomputed tomography
      has been used to visualize the development of the internal micro-structure within
      compressed tablets made from a combination of insoluble particles (Eudragit, a
      polymer) and soluble particles (diltiazem hydrochloride, a drug), during
      dissolution in water. Air voids in the tablet are seen to coarsen. The size
      distribution of the air voids is well fitted by a log-normal distribution with a
      mean size that grows linearly with time. There is evidence for both diffusion of
      voids and sudden collapse of individual voids, presumably as they coalesce. The
      behavior of the voids is studied and compared with models of coarsening; the
      implications for tablet dissolution are considered.

PMID- 16907098
TI  - Morphologies and flow patterns in quenching of lamellar systems with shear.
AB  - We study the behavior of a fluid quenched from the disordered into the lamellar
      phase under the action of a shear flow. The dynamics of the system is described
      by Navier-Stokes and convection-diffusion equations with the pressure tensor and
      the chemical potential derived by the Brazovskii free energy. Our simulations are
      based on a mixed numerical method with the lattice Boltzmann equation and a
      finite difference scheme for Navier-Stokes and order parameter equations,
      respectively. We focus on cases where banded flows are observed with two
      different slopes for the component of velocity in the direction of the applied
      flow. Close to the walls the system reaches a lamellar order with very few
      defects, and the slope of the horizontal velocity is higher than the imposed
      shear rate. In the middle of the system the local shear rate is lower than the
      imposed one, and the system looks like a mixture of tilted lamellae, droplets,
      and small elongated domains. We refer to this as a region with a shear-induced
      structures (SIS) configuration. The local behavior of the stress shows that the
      system with the coexisting lamellar and SIS regions is in mechanical equilibrium.
      This phenomenon occurs, at fixed viscosity, for shear rates under a certain
      threshold; when the imposed shear rate is sufficiently large, lamellar order
      develops in the whole system. Effects of different viscosities have been also
      considered. The SIS region is observed only at low enough viscosity. We compare
      the above scenario with the usual one of shear banding. In particular, we do not
      find evidence for a plateau of the stress at varying imposed shear rates in the
      region with banded flow. We interpret our results as due to a tendency of the
      lamellar system to oppose the presence of the applied flow.

PMID- 16907099
TI  - Transitions among crystal, glass, and liquid in a binary mixture with changing
      particle-size ratio and temperature.
AB  - Using molecular dynamics simulation we examine changeovers among crystal, glass,
      and liquid at high density in a two dimensional binary mixture. We change the
      ratio between the diameters of the two components and the temperature. The
      transitions from crystal to glass or liquid occur with proliferation of defects.
      We visualize the defects in terms of a disorder variable Dj(t) representing a
      deviation from the hexagonal order for particle j. The defect structures are
      heterogeneous and are particularly extended in polycrystal states. They look
      similar at the crystal-glass crossover and at the melting. Taking the average of
      Dj(t) over the particles, we define a disorder parameter D(t), which measures the
      degree of overall disorder. The relaxation of D(t) after quenching becomes slow
      at low temperature in the presence of size dispersity. Its steady state average
      is small in crystal and large in glass and liquid. We also find that grain
      boundaries tend to be pinned with increasing size dispersity in polycrystal
      states.

PMID- 16907100
TI  - Effects of quenching rate and viscosity on spinodal decomposition.
AB  - Spinodal decomposition of deeply quenched mixtures is studied experimentally,
      with particular emphasis on the domain growth rate during the late stage of
      coarsening. We provide some experimental evidence that at high Peclet number, the
      process is isotropic and the domain growth is linear in time, even at finite
      quenching rates. In fact, the quenching rate appears to influence the magnitude
      of the growth rate, but not its scaling law. In the second part of the work we
      analyze the effect of viscosity on the growth rate. As predicted by the diffuse
      interface model, we do not find any effect of viscosity on the growth rate of the
      nucleating drops, although, as expected, the viscosity of the continuous phase
      does influence the settling speed and thus the total separation time.

PMID- 16907101
TI  - Renormalization-group theory for the phase-field crystal equation.
AB  - We derive a set of rotationally covariant amplitude equations for use in
      multiscale simulation of the two-dimensional phase-field crystal model by a
      variety of renormalization-group (RG) methods. We show that the presence of a
      conservation law introduces an ambiguity in operator ordering in the RG
      procedure, which we show how to resolve. We compare our analysis with standard
      multiple-scale techniques, where identical results can be obtained with greater
      labor, by going to sixth order in perturbation theory, and by assuming the
      correct scaling of space and time.

PMID- 16907102
TI  - Effects of island disaggregation in growth models.
AB  - We introduced two point island models with island disaggregation. In the first
      one, particles can detach from islands with an odd number of particles and from
      those with two particles. In the second model, particles can detach from all
      islands with more than two particles. The scaling exponents are analytically
      obtained and verified with Monte Carlo simulations. Specially, the power-law
      scalings of the island and monomer densities are analyzed. Comparison with other
      models indicates that the models introduced here present different scaling
      behaviors.

PMID- 16907103
TI  - Surface and interfacial dynamics of polymeric bilayer films.
AB  - The theory for surface dynamics of the thermally excited fluctuations on a
      homogenous single-layer film of arbitrary depth is generalized to describe
      surface and interfacial dynamics of polymeric liquid bilayer films in terms of
      susceptibilities, power spectra, and characteristic relaxation time constants.
      The effects on surface dynamics originating from viscosity inhomogeneities close
      to the surface and interfacial regions are investigated by the bilayer theory and
      compared with the surface dynamics of homogeneous single-layer films under
      nonslip and slip boundary conditions. Our bilayer theory can also be extended to
      study interfacial dynamics of more generalized multilayer systems. The effects of
      viscoelasticity and van der Waals interactions on surface and interfacial
      dynamics are also briefly discussed.

PMID- 16907104
TI  - Universal and nonuniversal features in the crossover from linear to nonlinear
      interface growth.
AB  - We study a restricted solid-on-solid model involving deposition and evaporation
      with probabilities p and 1 - p, respectively, in one-dimensional substrates. It
      presents a crossover from Edwards-Wilkinson (EW) to Kardar-Parisi-Zhang (KPZ)
      scaling for p approximately 0.5. The associated KPZ equation is analytically
      derived, exhibiting a coefficient lambda of the nonlinear term proportional to q
      identical with p - 1/2, which is confirmed numerically by calculation of tilt
      dependent growth velocities for several values of p. This linear lambda - q
      relation contrasts to the apparently universal parabolic law obtained in
      competitive models mixing EW and KPZ components. The regions where the interface
      roughness shows pure EW and KPZ scaling are identified for 0.55< or =p< or =0.8,
      which provides numerical estimates of the crossover times tc. They scale as tc
      approximately lambda -phi with phi=4.1+/-0.1, which is in excellent agreement
      with the theoretically predicted universal value phi=4 and improves previous
      numerical estimates, which suggested phi approximately 3.

PMID- 16907105
TI  - Investigations of nanoscale helical pitch in smectic-C*alpha and smectic-C*
      phases of a chiral smectic liquid crystal using differential optical reflectivity
      measurements.
AB  - Differential optical reflectivity (DOR) was used to study the temperature
      dependence of the short helical pitch in freestanding films of a liquid crystal
      compound. The experimentally measured DOR signal was fitted using Berreman's 4 x
      4 matrix method to get the pitch value in the smectic-C*alpha (sMC*alpha) phase.
      The results show continuous evolution of the pitch between the smectic-C*alpha
      and sMC*alpha phases. In sMC*alpha, the pitch decreases as temperature increases
      and is found to level off at 16+/-1 smectic layers at the sMC*alpha to smectic-A*
      transition.

PMID- 16907106
TI  - Microscopic and macroscopic description of anchoring at the nematic-solid
      substrate interface.
AB  - A simple microscopic mean-field model for a flat nematic liquid crystal (NLC)
      sample in a contact to the solid substrate surface is offered. An interaction
      between NLC molecules is simulated by the well known McMillan model potential,
      and an orienting action of the solid substrate surface on NLC molecules is
      modeled by a short-range external field which acts directly only on molecules
      within the first molecular layer of the nematic sample adjacent to the substrate
      surface. For an undistorted NLC sample, the model allows the calculation of local
      order parameter profiles for different values of strength of this external
      orienting field and temperature of the sample. These profiles are used in a
      description of a director field distortion caused by a certain external action
      and in the calculation of the anchoring energy coefficient used in a macroscopic
      description of the anchoring at the nematic-solid substrate interface. Dependence
      of this coefficient on the strength of the short-range orienting field is
      obtained, and an unequivocal relation between the magnitude of and the
      orientational order parameter profile near the substrate surface is established.
      The temperature dependence of the coefficient W calculated from the offered
      microscopic model is in good agreement with the experimental data on NLC MBBA.

PMID- 16907107
TI  - Role of molecular weight and phase sequence in the temperature variation of film
      tension above the bulk isotropic transition in freestanding liquid-crystal films.
AB  - Building upon our previous report [Veum, Phys. Rev. E 17, 020701(R) (2005)]
      involving two compounds, we have performed a systematic study of the temperature
      variation of film tension above the bulk isotropic transition in freestanding
      films to include a total of six smectic liquid-crystal compounds. Consistent with
      the previous results, the tension increases sharply with temperature above the
      transition, the tension-temperature slope is proportional to the film's
      thickness, and the data can be interpreted in the context of theoretical models
      for layer thinning. Our data suggest that both molecular weight and bulk phase
      appearing below its isotropic phase play important roles in the slope values.

PMID- 16907108
TI  - Computer simulation study of a simple cubatic mesogenic lattice model.
AB  - Over the last , the possible existence of a cubatic mesophase, possessing cubic
      orientational order (i.e., along three mutually orthogonal axes) but no
      translational one, has been addressed theoretically, and predicted in some cases,
      where the investigated interaction models involved hard-core repulsion only; on
      the other hand, no experimental realizations of such a phase are known at the
      time being. The present paper addresses a very simple cubatic mesogenic lattice
      model, involving continuous interactions; we consider particles possessing Oh
      symmetry, whose centers of mass are associated with a three-dimensional simple
      cubic lattice; the pair potential is taken to be isotropic in orientation space,
      and restricted to nearest neighboring sites; let the two orthonormal triads {uj,
      j=1, 2, 3} and {vk, k=1, 2, 3} define orientations of a pair of interacting
      particles, and let fjk=vj.uk. The interaction model studied here is defined by
      the simplest nontrivial (quartic) polynomial in the scalar products f jk,
      consistent with the assumed symmetry and favoring orientational order; it is, so
      to speak, the cubatic counterpart of the Lebwohl-Lasher model for uniaxial
      nematics. The model was investigated by mean field theory and Monte Carlo
      simulation, and found to produce a low-temperature cubatically ordered phase,
      undergoing a first order transition to the isotropic phase at higher temperature;
      the mean field treatment yielded results in reasonable qualitative agreement with
      simulation.

PMID- 16907109
TI  - Theory of the intermediate tilted smectic phases and their helical rotation.
AB  - A molecular-statistical theory for the entire sequence of the chiral tilted
      smectic phases is derived. Uniaxial and biaxial subphases were found to be stable
      in different temperature ranges depending on the molecular parameters. The model
      of a chiral molecule possessing a strong transverse terminal dipole moment and a
      quadrupole moment located in the molecular core was used. Direct dispersion and
      electrostatic interactions (modulated by shape) between molecules located in the
      same or in the neighboring smectic layers are taken into account. An effective
      long-range interaction arises after the minimization of the free energy with
      respect to polarization vectors. If the molecular quadrupole moment is small,
      only uniaxial phases with different periodicities arise. Their periodicity may be
      tens and hundreds of layers (Sm-C*), or approximately two layers (Sm-C*)(Sm-C*A),
      or several layers (Sm-C*alpha). In the presence of the nonpolar biaxial ordering
      (in addition to polarization) there is a cap-shaped border in the phase diagram
      that separates Sm-C*A, Sm-C*, and Sm-C*alpha. If the molecules are nonchiral, Sm
      CA, Sm-C, and the de Vries's phases arise instead of the three phases mentioned
      above. If the molecular quadrupole moment is large, the left "arm" of the border
      breaks into two lines, and a sequence of biaxial subphases arises in the area
      between these two lines. Among these biaxial subphases, the one with periodicity
      of three smectic layers appears to be the broadest in the temperature range. In
      addition, the subphases with different periodicities were found to be stable in
      narrow temperature ranges. The long helical rotation in every biaxial subphase is
      calculated. It is found to change sign between the three-layer subphase and Sm
      C*, and may diverge in the four-layer subphase if it arises. All calculations are
      done with help of (A)FLC Phase Diagram Plotter software developed by the first
      author and available at his web-page.

PMID- 16907110
TI  - Memory effects in nematics with quenched disorder.
AB  - We present a combined experimental and Monte Carlo study of a nematic phase in
      the presence of quenched disorder. The turbidity of a nematic liquid crystal
      embedded in a porous polymer membrane is measured under different applied field
      conditions for field-cooled and zero-field-cooled samples. We find that a
      significant permanent alignment of the nematic can be induced by fields as low as
      0.1 V/microm applied during the isotropic to nematic transition. An analogous
      effect and dependence on sample history is found by studying the order parameter
      of a sprinkled disorder Lebwohl-Lasher spin model, indicating that dilute
      quenched randomness is sufficient to produce memory effects in nematics. The
      large memory induced by field cooling appears to be written in the system during
      the transition as a result of the field action on freely oriented nematic nuclei.
      At lower temperature the nuclei consolidate into permanent nematic textures
      developed from the interaction with quenched disorder.

PMID- 16907111
TI  - Optical and electro-optical derivation of the pretransitional behavior of
      orientational and shear viscosities in the isotropic phase of liquid crystals.
AB  - The pretransitional equilibrium properties of isotropic liquids in the proximity
      of the isotropic-nematic phase transition are well known and successfully
      modeled. Much less is known about the dynamic behavior, and in particular about
      the pretransitional viscosity. In this work we combine two techniques [dynamic
      light scattering (DLS) and electric birefringence spectroscopy (EBS)] offering
      complementary insights into both static and dynamic pretransitional behavior of
      the homologous nCB family (n-alkyl cyanobiphenyl). EBS explores the single
      molecule flipping dynamics retarded by a paranematic potential barrier and
      enables extracting the associated transport coefficient, which is found to be of
      Arrhenius type in the whole temperature range explored. DLS reflects the
      collective dynamics of correlated domains and depends on the viscous damping of
      the orientational order. Such a viscosity displays Arrhenius behavior only
      sufficiently far from the transition temperature, with deviations growing as a
      power law of the appropriate reduced temperature with exponents around 0.1.

PMID- 16907112
TI  - Dispersion of the ordinary refractive indices of smectic liquid crystals in free
      standing films.
AB  - The ordinary refractive indices of some smectic-A liquid crystals have been
      measured by means of interference spectra of free standing films as a function of
      wavelength and temperature. Numerical data are presented for further use. In the
      Sm-C phase one of the principal indices can be measured. If the three principal
      indices in the Sm-C phase would be known the tilt angle could be measured by
      means of the interference technique with high precision. Predictions of the
      refractive index of liquid crystals based on quantum chemical calculations of
      polarizabilities are presented. Using an expression derived by de Jeu and
      Bordewijk [J. Chem. Phys. 68, 109 (1978)] values for the principal refractive
      indices have been calculated that can be compared with our experimental results.

PMID- 16907113
TI  - Capillary effects in a confined smectic phase of hard spherocylinders: influence
      of particle elongation.
AB  - A system of hard rods confined into a pore with slit geometry (two parallel
      planar substrates) is studied theoretically in the regime of high packing
      fraction. In this regime the bulk system exhibits a nematic phase as well as a
      smectic-A (spatially layered) phase. When the system is confined, strong
      commensuration effects between the layer spacing and the pore width bring about a
      rich phenomenology, with a phase diagram showing layering and capillary
      transitions. The latter include capillary smectization transitions whereby a
      confined smectic phase occurs at conditions of saturation different from those of
      the corresponding bulk fluid. These transitions are seen to be intimately
      connected with layering transitions involving discontinuous changes in the number
      of layers inside the pore. This rich phenomenology is obtained by use of a
      sophisticated density-functional, Onsager-theory-based approach, especially
      suited to deal with strongly inhomogeneous fluids. The theory allows for a
      unified description of ordering and phase behavior of the fluid in confined
      geometry, and permits us to correlate the above behavior with the wetting
      properties of the fluid on a single substrate.

PMID- 16907114
TI  - Liquid crystal model of membrane flexoelectricity.
AB  - An interfacial liquid crystal model is formulated and used to derive a membrane
      shape equation that takes into account pressure, tension, bending, torsion, and
      flexoelectric forces. Flexoelectricity introduces electric field-induced
      curvature and is of relevance to the study and characterization of biological
      membranes. It is shown that flexoelectricity renormalizes the membrane mechanical
      tension, shear, and bending effects, and hence it offers diverse pathways to
      manipulate the membrane's shape. The derived electroelastic shape equation
      provides systematic guidance on how to use electric fields in membrane studies.

PMID- 16907115
TI  - Anisotropic nanoparticles immersed in a nematic liquid crystal: defect structures
      and potentials of mean force.
AB  - We report results for the potential of mean force (PMF) and the defect structures
      that arise when spherocylindrical nanoparticles are immersed in a nematic liquid
      crystal. Using a dynamic field theory for the tensor order parameter Q of the
      liquid crystal, we analyzed configurations, including one, two, and three
      elongated particles, with strong homeotropic anchoring at their surfaces. For
      systems with one nanoparticle, the most stable configuration is achieved when the
      spherocylinder is placed with its long axis perpendicular to the far-field
      director, for which the defect structure consists of an elongated Saturn ring.
      For systems with two or three nanoparticles with their long axes placed
      perpendicular to the far-field director, at small separations the defect
      structures consist of incomplete Saturn rings fused with new disclination rings
      orthogonal to the original ones, in analogy to results previously observed for
      spherical nanoparticles. The shape of these orthogonal rings depends on the
      nanoparticles' configuration, i.e., triangular, linear, or parallel with respect
      to their long axis. A comparison of the PMFs indicates that the latter
      configuration is the most stable. The stability of the different arrays depends
      on whether orthogonal disclination rings form or not, their size, and the
      curvature effects in the interparticle regions. Our results suggest that the one
      elastic-constant approximation is valid for the considered systems; similar
      results were obtained when a three-constant expression is used to represent the
      elastic free energy. The attractive interactions between the elongated particles
      were compared to those observed for spheres of similar diameters. Similar
      interparticle energies were observed for linear arrays; in contrast, parallel and
      triangular arrays of spherocylinders yielded interactions that were up to 3.4
      times stronger than those observed for spherical particles.

PMID- 16907116
TI  - Undulations of lamellar liquid crystals in cells with finite surface anchoring
      near and well above the threshold.
AB  - We study the undulations instability, also known as the Helfrich-Hurault or
      layers buckling effect, in a cholesteric liquid crystal confined between two
      parallel plates and caused by an electric field applied along the normal to
      layers. The cholesteric pitch is much smaller than the cell thickness but
      sufficiently large for optical study. The three-dimensional patterns of the
      undulating layers in the bulk and at the surfaces of the cells are determined by
      fluorescence confocal polarizing microscopy. We demonstrate that the finite
      surface anchoring at the bounding plates plays a crucial role in the system
      behavior both near and well above the undulations threshold. The displacement of
      the layers immediately above the undulation threshold is much larger than the
      value expected from the theories that assume an infinitely strong surface
      anchoring. We describe the experimentally observed features by taking into
      account the finite surface anchoring at the bounding plates and using Lubensky-de
      Gennes coarse-grained elastic theory of cholesteric liquid crystals. Fitting the
      data allows us to determine the polar anchoring coefficient Wp and shows that Wp
      varies strongly with the type of substrates. As the applied field increases well
      above the threshold value Ec, the layers profile changes from sinusoidal to the
      sawtooth one. The periodicity of distortions increases through propagation of
      edge dislocations in the square lattice of the undulations pattern. At E
      approximately 1.9Ec a phenomenon is observed: the two-dimensional square lattice
      of undulations transforms into the one-dimensional periodic stripes. The stripes
      are formed by two sublattices of defect walls of parabolic shape. The main reason
      for the structure is again the finite surface anchoring, as the superposition of
      parabolic walls allows the layers to combine a significant tilt in the bulk of
      the cell with practically unperturbed orientation of layers near the bounding
      plates.

PMID- 16907117
TI  - Breakup of spiral and concentric ringed spherulites in polymer crystallization.
AB  - Recently, the breakup of spiral and concentric ringed spherulites has been
      observed experimentally in isothermal crystallization of poly(vinylidene
      fluoride) in its blends with ethylene vinyl acetate copolymer. To elucidate the
      phenomenon of spiral breakup in polymer spherulites, a theoretical simulation has
      been undertaken in the framework of the phase field model of solidification based
      on time-dependent Ginzburg-Landau equations (TDGL model C) pertaining to the
      conserved concentration and nonconserved phase field order parameters. The
      concentration order parameter was described in terms of the Landau-type
      potential, while the crystal order parameter was expressed in terms of an
      asymmetric double-well potential to account for the nonequilibrium nature (i.e.,
      metastability) of polymer crystallization. After inserting these potentials into
      the TDGL model C, the resulting coupled time-evolution equations show the
      emergence of the target and spiral patterns that undergo fragmentation at a very
      shallow supercooling. It is concluded that the depth of supercooling is the major
      contributor to the formation of the spirals and subsequent breakup of the spiral
      arms.

PMID- 16907118
TI  - Phenomenological analysis of the light intensity dependence of the photoalignment
      process in azo-containing polymeric films.
AB  - A phenomenological model is proposed to analyze the influence of the incident
      light intensity on the photoinduced anisotropy of an azobenzene-containing
      polymer film. The optical anisotropy was generated in the films by the incidence
      of linearly polarized light and monitored by transmittance measurements.

PMID- 16907119
TI  - Landau theory of the orthorhombic Fddd phase.
AB  - Numerical self-consistent-field theory calculations by Tyler and Morse [Phys.
      Rev. Lett. 94, 208302 (2005)] predict a stable orthorhombic network phase with
      space group in very weakly segregated diblock copolymer melts. Here, we examine
      the predicted stability of this phase within a simple Landau theory of weakly
      ordered crystals, and within a straightforward extension of Leibler's theory of
      weakly segregated diblock copolymer melts. An Fddd structure with a ratio of unit
      cell parameters (a:b:c)=(1:2:2 square root 3) is found to compete very closely
      with the hexagonal (H) and lamellar (L) phases along the predicted H-L phase
      boundary, and to be stable within a very narrow range of parameters around this
      metastable boundary.

PMID- 16907120
TI  - Spinodal decomposition via surface diffusion in polymer mixtures.
AB  - We present experimental results for spinodal decomposition in polymer mixtures of
      gelatin and dextran. The domain growth law is found to be consistent with t 1/4
      growth over extended time regimes. Similar results are obtained from lattice
      simulations of a polymer mixture. This slow growth arises due to the suppression
      of the bulk mobility of polymers. In that case, spinodal decomposition is driven
      by the diffusive transport of material along domain interfaces, which gives rise
      to a t 1/4 growth law.

PMID- 16907121
TI  - Coevolutionary dynamics in large, but finite populations.
AB  - Coevolving and competing species or game-theoretic strategies exhibit rich and
      complex dynamics for which a general theoretical framework based on finite
      populations is still lacking. Recently, an explicit mean-field description in the
      form of a Fokker-Planck equation was derived for frequency-dependent selection
      with two strategies in finite populations based on microscopic processes [A.
      Traulsen, J. C. Claussen, and C. Hauert, Phys. Rev. Lett. 95, 238701 (2005)].
      Here we generalize this approach in a twofold way: First, we extend the framework
      to an arbitrary number of strategies and second, we allow for mutations in the
      evolutionary process. The deterministic limit of infinite population size of the
      frequency-dependent Moran process yields the adjusted replicator-mutator
      equation, which describes the combined effect of selection and mutation. For
      finite populations, we provide an extension taking random drift into account. In
      the limit of neutral selection, i.e., whenever the process is determined by
      random drift and mutations, the stationary strategy distribution is derived. This
      distribution forms the background for the coevolutionary process. In particular,
      a critical mutation rate uc is obtained separating two scenarios: above uc the
      population predominantly consists of a mixture of strategies whereas below uc the
      population tends to be in homogeneous states. For one of the fundamental problems
      in evolutionary biology, the evolution of cooperation under Darwinian selection,
      we demonstrate that the analytical framework provides excellent approximations to
      individual based simulations even for rather small population sizes. This
      approach complements simulation results and provides a deeper, systematic
      understanding of coevolutionary dynamics.

PMID- 16907122
TI  - Unified modeling of conductance kinetics for low- and high-conductance potassium
      ion channels.
AB  - A kinetics model is proposed for the description of ion conductance of low- and
      high-conductance potassium ion channels. The model describes ion permeation
      through the selectivity filter, which is assumed to be the only conductance
      determining part of the open channel. The filter occupancy can vary from zero to
      three ions, affecting the ion entry and exit rates. Ion motion between the
      binding sites inside the filter is assumed fast compared to the latter rates
      allowing averaging the equilibrium entry and exit rate constants over the
      possible ion configurations in the filter with a particular occupancy. Averaged
      rate constants related to a pair of adjacent occupancy states characterize a
      particular ion permeation mechanism. An expression for the channel conductance as
      a function of the symmetrical external ion concentration is derived. It comprises
      a sum of concentration independent conductance amplitudes for different ion
      permeation mechanisms weighted by the equilibrium filter occupancy probabilities.
      It is shown that each amplitude (i.e., maximum contribution to the channel
      conductance from each conductance mechanism) is proportional to an averaged exit
      rate constant and to quantities characterizing the effect of the applied electric
      field on the rate constants and the equilibrium ion distribution in the filter.
      The conductance expression derived provides a good description of the
      experimentally observed conductance-concentration curves for low-conductance
      (e.g., Kir2.1) and high-conductance (e.g., KcsA) potassium channels. It enables
      one to obtain equilibrium ion binding constants at different filter occupancies
      and to calculate the average number of ions in the selectivity filter for a given
      external ion concentration. For KcsA this number (2.0 at 200 mM) is in a good
      agreement with the available experimental value (2.1 at 200 mM). For the high
      conductance potassium channels the net negative electrical charge around the
      selectivity filter increases the ion binding constants, thereby causing the
      larger occupancy probabilities to occur at smaller external ion concentrations
      compared to the low-conductance channels. This substantially increases the
      contributions of the two- and three-ion permeation mechanisms, with the larger
      conductance amplitudes leading to increased channel conductance compared to the
      low-conductance channels.

PMID- 16907123
TI  - Condition for intracellular adaptive dynamics for chemotaxis.
AB  - Chemotaxis is ubiquitously performed by bacteria. They sense and move toward a
      region with a higher concentration of an attractive chemical by changing the rate
      of tumbling for random walk. We numerically studied several models with internal
      adaptive dynamics to examine the validity of the condition for chemotaxis
      proposed by Oosawa and Nakaoka [J. Theor. Biol. 66, 747 (1977)], which states
      that the time scale of tumbling frequency must be smaller than that of adaptation
      and greater than that of sensing. Suitable renormalization of the time scales
      showed that the condition holds for a variety of environments and for both short-
      and long-term behavior.

PMID- 16907124
TI  - DNA charge neutralization by linear polymers: irreversible binding.
AB  - We develop a deterministic mathematical model to describe the way in which
      polymers bind to DNA by considering the dynamics of the gap distribution that
      forms when polymers bind to a DNA plasmid. In so doing, we generalize existing
      theory to account for overlaps and binding cooperativity whereby the polymer
      binding rate depends on the size of the overlap. The proposed mean-field models
      are then solved using a combination of numerical and asymptotic methods. We find
      that overlaps lead to higher coverage and hence higher charge neutralizations,
      results which are more in line with recent experimental observations. Our work
      has applications to gene therapy where polymers are used to neutralize the
      negative charges of the DNA phosphate backbone, allowing condensation prior to
      delivery into the nucleus of an abnormal cell.

PMID- 16907125
TI  - Energy aspects of the synchronization of model neurons.
AB  - We have deduced an energy function for a Hindmarsh-Rose model neuron and we have
      used it to evaluate the energy consumption of the neuron during its signaling
      activity. We investigate the balance of energy in the synchronization of two
      bidirectional linearly coupled neurons at different values of the coupling
      strength. We show that when two neurons are coupled there is a specific cost
      associated to the cooperative behavior. We find that the energy consumption of
      the neurons is incoherent until very near the threshold of identical
      synchronization, which suggests that cooperative behaviors without complete
      synchrony could be energetically more advantageous than those with complete
      synchrony.

PMID- 16907126
TI  - Fluctuation theorems and the nonequilibrium thermodynamics of molecular motors.
AB  - The fluctuation theorems for the currents and the dissipated work are considered
      for molecular motors which are driven out of equilibrium by chemical reactions.
      Because of the molecular fluctuations, these nonequilibrium processes are
      described by stochastic models based on a master equation. Analytical expressions
      are derived for the fluctuation theorems, allowing us to obtain predictions on
      the work dissipated in the motor as well as on its rotation near and far from
      thermodynamic equilibrium. We show that the fluctuation theorems provide a method
      to determine the affinity or thermodynamic force driving the motor. This affinity
      is given in terms of the free enthalpy of the chemical reactions. The theorems
      are applied to the F1 rotary motor which turns out to be a stiff system typically
      functioning in the nonlinear regime of nonequilibrium thermodynamics. We show
      that this nonlinearity confers a robustness to the functioning of the molecular
      motor.

PMID- 16907127
TI  - Analytical theory of the nonequilibrium spatial distribution of RNA polymerase
      translocations.
AB  - A continuum Fokker-Planck model is considered for the RNA polymerase in the
      elongation phase, where the topology of a single free energy profile as a
      function of the translocation variable distinguishes the Brownian ratchet and
      power stroke mechanisms. The model yields a simple analytical stationary solution
      for arbitrary functional forms of the free energy. With the translocation
      potential of mean force estimated by the time-series data of the recent high
      resolution single-molecule experiment [Abbondanzieri et al., Nature (London) 438,
      460 (2005)], predictions of the model for the mechanical properties agree with
      experiments quantitatively with reasonable values of parameters. The evolution of
      the spatial distribution of translocation variable away from equilibrium with
      increasing nucleoside triphosphate concentration shows qualitatively different
      behavior in the two alternative scenarios, which could serve as an additional
      measurable signature of the underlying mechanism.

PMID- 16907128
TI  - Pacemaker activity resulting from the coupling with nonexcitable cells.
AB  - Fibroblasts are nonexcitable cells that are sometimes coupled with excitable
      cells (cardiomyocytes). Due to a higher resting potential, these cells may act as
      a current source or sink and therefore disturb the electrical activity of the
      surrounding excitable cells. The possible occurrence of spontaneous pacemaker
      activity resulting from these electrotonic interactions was investigated in a
      theoretical model of two coupled cells as well as in a multicellular fiber model
      based on the Courtemanche kinetics. The results indicate that repeated
      spontaneous activations can be observed after an alteration in the activation and
      recovery properties of the sodium current (changes in excitability properties),
      provided that the difference in the resting potential as well as the coupling
      between the excitable and nonexcitable cells is sufficiently high. This may
      constitute a mechanism of focal sources triggering arrhythmias such as atrial
      fibrillation.

PMID- 16907129
TI  - Stochastic dynamics of invasion and fixation.
AB  - We study evolutionary game dynamics in finite populations. We analyze an
      evolutionary process, which we call pairwise comparison, for which we adopt the
      ubiquitous Fermi distribution function from statistical mechanics. The inverse
      temperature in this process controls the intensity of selection, leading to a
      unified framework for evolutionary dynamics at all intensities of selection, from
      random drift to imitation dynamics. We derive a simple closed formula that
      determines the feasibility of cooperation in finite populations, whenever
      cooperation is modeled in terms of any symmetric two-person game. In contrast
      with previous results, the present formula is valid at all intensities of
      selection and for any initial condition. We investigate the evolutionary dynamics
      of cooperators in finite populations, and study the interplay between intensity
      of selection and the remnants of interior fixed points in infinite populations,
      as a function of a given initial number of cooperators, showing how this
      interplay strongly affects the approach to fixation of a given trait in finite
      populations, leading to counterintuitive results at different intensities of
      selection.

PMID- 16907130
TI  - T-cell motility in the early stages of the immune response modeled as a random
      walk amongst targets.
AB  - The transport process by which a T cell makes high-frequency encounters with
      antigen-presenting cells following infection is an important element of adaptive
      immunity. Recent experimental work has allowed in vivo cell motility to be
      characterized in detail. On the basis of experimental data we develop a
      quantitative model for encounters between T cells and antigen-presenting cells.
      We model this as a transport-limited chemical reaction with the dynamics
      dependent on physical contact between randomly moving reactants. We use
      asymptotic methods to calculate a time distribution which characterizes the delay
      before a T cell is activated and use Monte Carlo simulations to verify the
      analysis. We find that the density of antigen-primed dendritic cells within the
      lymph node paracortex must be greater than 35 cells/mm3 for a T cell to have a
      more than 50% chance of encountering a dendritic cell within 24 h. This density
      is much larger than existing estimates based on calculations which neglect the
      transport process. We also use simulations to compare a T cell which re-orients
      isotropically with a T cell which turns according to an experimentally observed
      distribution and find that the effects of anisotropy on the solution are small.

PMID- 16907131
TI  - Driven translocation of a polynucleotide chain through a nanopore: a continuous
      time Monte Carlo study.
AB  - Using the continuous time Monte Carlo method, we simulated the translocation of a
      polynucleotide chain driven through a nanopore by an electric field. We have used
      two models of driven diffusion due to the electric field. The chain may have
      strong interaction with the pore, and depends on which end of the chain first
      enters the pore. Depending on this interaction, in both cases, the distribution
      of times for the chain to pass through the pore in our model is found to have
      three peaks, as observed in the experiment of Kasianowicz Brandin, Branton, and
      Deamer [Proc. Natl. Acad. Sci. USA 93, 13770 (1996)].

PMID- 16907132
TI  - Brownian molecular motors driven by rotation-translation coupling.
AB  - We investigated three models of Brownian motors which convert rotational
      diffusion into directed translational motion by switching on and off a potential.
      In the first model a spatially asymmetric potential generates directed
      translational motion by rectifying rotational diffusion. It behaves much like a
      conventional flashing ratchet. The second model utilizes both rotational
      diffusion and drift to generate translational motion without spatial asymmetry in
      the potential. This second model can be driven by a combination of a Brownian
      motor mechanism (diffusion driven) or by powerstroke (drift driven) depending on
      the chosen parameters. In the third model, elements of both the Brownian motor
      and powerstroke mechanisms are combined by switching between three distinct
      states. Relevance of the model to biological motor proteins is discussed.

PMID- 16907133
TI  - Analyses of simulations of three-dimensional lattice proteins in comparison with
      a simplified statistical mechanical model of protein folding.
AB  - Folding and unfolding simulations of three-dimensional lattice proteins were
      analyzed using a simplified statistical mechanical model in which their amino
      acid sequences and native conformations were incorporated explicitly. Using this
      statistical mechanical model, under the assumption that only interactions between
      amino acid residues within a local structure in a native state are considered,
      the partition function of the system can be calculated for a given native
      conformation without any adjustable parameter. The simulations were carried out
      for two different native conformations, for each of which two foldable amino acid
      sequences were considered. The native and non-native contacts between amino acid
      residues occurring in the simulations were examined in detail and compared with
      the results derived from the theoretical model. The equilibrium thermodynamic
      quantities (free energy, enthalpy, entropy, and the probability of each amino
      acid residue being in the native state) at various temperatures obtained from the
      simulations and the theoretical model were also examined in order to characterize
      the folding processes that depend on the native conformations and the amino acid
      sequences. Finally, the free energy landscapes were discussed based on these
      analyses.

PMID- 16907134
TI  - Two-stage Turing model for generating pigment patterns on the leopard and the
      jaguar.
AB  - Based on the results of phylogenetic analysis, which showed that flecks are the
      primitive pattern of the felid family and all other patterns including rosettes
      and blotches develop from it, we construct a Turing reaction-diffusion model
      which generates spot patterns initially. Starting from this spotted pattern, we
      successfully generate patterns of adult leopards and jaguars by tuning parameters
      of the model in the subsequent phase of patterning.

PMID- 16907135
TI  - Cellular tolerance to pulsed hyperthermia.
AB  - Transient heating of tissues leading to cellular stress or death is very common
      in medicine and biology. In procedures involving a mild (below 70 degrees C) and
      prolonged (minutes) heating, such as hyperthermal tumor therapy, the cellular
      response to thermal stress is relatively well studied. However, there is
      practically no data on cell viability at higher temperatures and shorter
      exposures, while the demand for this knowledge is growing. Two main reasons
      motivate this research: (i) a growing number of laser therapies and surgical
      procedures involving pulsed heating, and (ii) cellular viability data at short
      exposures to high temperatures provide a unique insight into the understanding of
      processes leading to thermally induced cellular death. We designed a technique
      and performed a study of cell viability under pulses of heat from 0.3 to 100 ms
      in duration with peak temperatures as high as 130 degrees C. We found that the
      threshold of cellular death in this range can be accurately approximated by the
      Arrhenius law with the activation energy of 1 eV, a significantly lower value
      than was reported in studies based on multisecond exposures.

PMID- 16907136
TI  - Spatiotemporal fluctuation-induced transition in a tumor model with immune
      surveillance.
AB  - We report on a simple model of spatially extended antitumor system with a
      fluctuation in growth rate, which can undergo a nonequilibrium phase transition.
      Three states as excited, subexcited and nonexcited states of a tumor are defined
      to describe its growth. The multiplicative noise is found to have opposite
      effects: The positive effect on a nonexcited tumor and the negative effect on an
      excited tumor.

PMID- 16907137
TI  - Simple data-driven models of intracellular calcium dynamics with predictive
      power.
AB  - Biology is complex. However, it is not clear how much of this complexity must
      necessarily translate into complicated mathematical models of biological
      processes. Simple models can be appealing to physicists but are usually deceiving
      for biologists. Complicated models, on the other hand, depend on too many
      parameters whose values are frequently unknown. Therefore, complicated models,
      although in principle more realistic, can lead to erroneous results if they are
      sensitive to these unknown parameter values. Intracellular calcium signals
      provide an example of utmost biological importance in which the issue of "simple
      vs complex" can be explored. In this paper we show that simple models describing
      the dynamics of intracellular calcium can be directly inferred from experimental
      data, without no a priori information on unknown parameters. A similar approach
      can be followed to study other reaction-diffusion systems. In spite of their
      simplicity, these models can provide quantitative information on some of the
      processes that shape calcium signals, such as the calcium current that underlies
      an experimental observation. This shows that simple models of biological systems
      are not limited to qualitative descriptions.

PMID- 16907138
TI  - Stable propagation of a burst through a one-dimensional homogeneous excitatory
      chain model of songbird nucleus HVC.
AB  - We demonstrate numerically that a brief burst consisting of two to six spikes can
      propagate in a stable manner through a one-dimensional homogeneous feedforward
      chain of nonbursting neurons with excitatory synaptic connections. Our results
      are obtained for two kinds of neuronal models: leaky integrate-and-fire neurons
      and Hodgkin-Huxley neurons with five conductances. Over a range of parameters
      such as the maximum synaptic conductance, both kinds of chains are found to have
      multiple attractors of propagating bursts, with each attractor being
      distinguished by the number of spikes and total duration of the propagating
      burst. These results make plausible the hypothesis that sparse, precisely timed
      sequential bursts observed in projection neurons of nucleus HVC of a singing
      zebra finch are intrinsic and causally related.

PMID- 16907139
TI  - Characterization of the tunneling conductance across DNA bases.
AB  - Characterization of the electrical properties of the DNA bases (adenine,
      cytosine, guanine, and thymine), in addition to building the basic knowledge on
      these fundamental constituents of a DNA, is a crucial step in developing a DNA
      sequencing technology. We present a first-principles study of the current-voltage
      characteristics of nucleotidelike molecules of the DNA bases, placed in a 1.5 nm
      gap formed between gold nanoelectrodes. The quantum transport calculations in the
      tunneling regime are shown to vary strongly with the electrode-molecule geometry
      and the choice of the density-functional theory exchange-correlation functionals.
      Analysis of the results in the zero-bias limit indicates that distinguishable
      current-voltage characteristics of different DNA bases are dominated by the
      geometrical conformations of the bases and nanoelectrodes.

PMID- 16907140
TI  - Perturbation analysis for competing reactions with initially separated
      components.
AB  - We study a competitive reaction-diffusion system with initially separated
      components. In this system, two similar species on one side of the system compete
      to react with the species on the other side. The competition is due to
      significant differences in the microscopic reaction constants and the initial
      densities of the two competing species. In the short-time limit, each of the
      competitive reactions is considered as perturbation with respect to the
      diffusion, the latter is essential for the effective mixing of the reactants. We
      identify the small parameters required for the perturbation analysis of the
      competitive scheme. The resulting perturbative expressions provide the rich
      spatiotemporal reaction front patterns, which were experimentally observed for
      Cr3+ + Xylenol Orange (XO) --> products, where the aggregated and nonaggregated
      forms of Cr3+ in aqueous solution compete to react with the XO.

PMID- 16907141
TI  - Macroscopic description of particle systems with nonlocal density-dependent
      diffusivity.
AB  - In this paper we study macroscopic density equations in which the diffusion
      coefficient depends on a weighted spatial average of the density itself. We show
      that large differences (not present in the local density-dependence case) appear
      between the density equations that are derived from different representations of
      the Langevin equation describing a system of interacting Brownian particles.
      Linear stability analysis demonstrates that under some circumstances the density
      equation interpreted with the Ito calculus has pattern solutions that never
      appear for the kinetic interpretation, which is the other one typically appearing
      in the context of nonlinear diffusion processes. We also introduce a discrete
      time microscopic model of particles that confirms the results obtained at the
      macroscopic density level.

PMID- 16907142
TI  - Actin-based propulsion of a microswimmer.
AB  - A simple hydrodynamic model of actin-based propulsion of microparticles in dilute
      cell-free cytoplasmic extracts is presented. Under the basic assumption that
      actin polymerization at the particle surface acts as a force dipole, pushing
      apart the load and the free (nonanchored) actin tail, the propulsive velocity of
      the microparticle is determined as a function of the tail length, porosity, and
      particle shape. The anticipated velocities of the cargo displacement and the
      rearward motion of the tail are in good agreement with recently reported results
      of biomimetic experiments. A more detailed analysis of the particle-tail
      hydrodynamic interaction is presented and compared to the prediction of the
      simplified model.

PMID- 16907143
TI  - Fjords in viscous fingering: selection of width and opening angle.
AB  - Our experiments on viscous fingering of air into oil contained between closely
      spaced plates reveal two selection rules for the fjords of oil that separate
      fingers of air. (Fjords are the building blocks of solutions of the zero-surface
      tension Laplacian growth equation.) Experiments in rectangular and circular
      geometries yield fjords with base widths lambda(c)/2, where lambda(c) is the most
      unstable wavelength from a linear stability analysis. Further, fjords open at an
      angle of 8.0 degrees +/- 1.0 degree. These selection rules hold for a wide range
      of pumping rates and fjord lengths, widths, and directions.

PMID- 16907144
TI  - Self-organization of chaos synchronization and pattern formation in coupled
      chaotic oscillators.
AB  - Pattern formation in spatiotemporal chaotic systems is investigated. Temporally
      chaotic and spatially ordered patterns are observed by varying the coupling
      strength. Spatial orderings emerge spontaneously due to self-organization of
      partial and nonlocal chaos synchronization, governed by various types of spatial
      symmetries. The first and secondary bifurcations from spatially disordered chaos
      to chaos with different levels of spatial orderings are observed and the scaling
      behaviors associated with these bifurcations are statistically analyzed.

PMID- 16907145
TI  - Integrating local static and dynamic information for routing traffic.
AB  - The efficiency of traffic routing on complex networks can be reflected by two key
      measurements, i.e., the network capacity and the average travel time of data
      packets. In this paper we propose a mixing routing strategy by integrating local
      static and dynamic information for enhancing the efficiency of traffic on scale
      free networks. The strategy is governed by a single parameter. Simulation results
      show that maximizing the network capacity and reducing the packet travel time can
      generate an optimal parameter value. Compared with the strategy of adopting
      exclusive local static information, the new strategy shows its advantages in
      improving the efficiency of the system. The detailed analysis of the mixing
      strategy is provided for explaining its effects on traffic routing. The work
      indicates that effectively utilizing the larger degree nodes plays a key role in
      scale-free traffic systems.

PMID- 16907146
TI  - Synchronization in dynamical networks: evolution along commutative graphs.
AB  - Starting from an initial wiring of connections, we show that the
      synchronizability of a network can be significantly improved by evolving the
      graph along a time dependent connectivity matrix. We consider the case of
      connectivity matrices that commute at all times, and compare several approaches
      to engineer the corresponding commutative graphs. In particular, we show that
      synchronization in a dynamical network can be achieved even in the case in which
      each individual commutative graphs does not give rise to synchronized behavior.

PMID- 16907147
TI  - Wavelet versus detrended fluctuation analysis of multifractal structures.
AB  - We perform a comparative study of applicability of the multifractal detrended
      fluctuation analysis (MFDFA) and the wavelet transform modulus maxima (WTMM)
      method in proper detecting of monofractal and multifractal character of data. We
      quantify the performance of both methods by using different sorts of artificial
      signals generated according to a few well-known exactly soluble mathematical
      models: monofractal fractional Brownian motion, bifractal Levy flights, and
      different sorts of multifractal binomial cascades. Our results show that in the
      majority of situations in which one does not know a priori the fractal properties
      of a process, choosing MFDFA should be recommended. In particular, WTMM gives
      biased outcomes for the fractional Brownian motion with different values of Hurst
      exponent, indicating spurious multifractality. In some cases WTMM can also give
      different results if one applies different wavelets. We do not exclude using WTMM
      in real data analysis, but it occurs that while one may apply MFDFA in a more
      automatic fashion, WTMM must be applied with care. In the second part of our
      work, we perform an analogous analysis on empirical data coming from the American
      and from the German stock market. For this data both methods detect rich
      multifractality in terms of broad f(alpha), but MFDFA suggests that this
      multifractality is poorer than in the case of WTMM.

PMID- 16907148
TI  - Preseismic electromagnetic signals in terms of complexity.
AB  - There is a recent thesis in the literature that an important organization of a
      physical system precedes a catastrophic event. In this context, one can search
      for signatures that imply the transition from a normal state to a main
      catastrophic event (e.g., earthquake). Experimental techniques are thus useful in
      corroborating theories from observed data. For example, recent results indicate
      that preseismic electromagnetic time series contain information characteristic of
      an ensuing earthquake event. Hereby, we attempt to demonstrate that an easily
      computable complexity measure, such as T-complexity or approximate entropy, gives
      evidence of state changes leading to the point of global instability. The
      appearance of a precatastrophic state is characterized by significant lower
      complexity in terms of T-complexity and approximate entropy. The present study
      confirms the conclusions of previous works based on an independent linear fractal
      spectral analysis. This convergence between nonlinear and linear analysis
      provides a more reliable detection concerning the emergence of the last phase of
      the earthquake preparation process. More precisely, we claim that our results
      suggest an important principle: significant complexity decrease and accession of
      persistency in electromagnetic (EM) time series can be confirmed at the tail of
      the preseismic EM emission, which could be used as diagnostic tools for the
      Earth's impending crust failure. Direct laboratory and field experimental data as
      well as theoretical arguments support the conclusions of the present analysis.

PMID- 16907149
TI  - Network community structure and loop coefficient method.
AB  - A modular structure, in which groups of tightly connected nodes could be resolved
      as separate entities, is a property that can be found in many complex networks.
      In this paper, we propose a algorithm for identifying communities in networks. It
      is based on a local measure, so-called loop coefficient that is a generalization
      of the clustering coefficient. Nodes with a large loop coefficient tend to be
      core inner community nodes, while other vertices are usually peripheral sites at
      the borders of communities. Our method gives satisfactory results for both
      artificial and real-world graphs, if they have a relatively pronounced modular
      structure. This type of algorithm could open a way of interpreting the role of
      nodes in communities in terms of the local loop coefficient, and could be used as
      a complement to other methods.

PMID- 16907150
TI  - Some analytical results for the velocity of cracks propagating in nonlinear
      lattices.
AB  - We analyze a piecewise linear elastic model for the propagation of a crack in a
      stripe geometry under mode III conditions, in the absence of dissipation. The
      model is continuous in the propagation direction and discrete in the
      perpendicular direction. The velocity of the crack is a function of the value of
      the applied strain. We find analytically the value of the propagation velocity
      close to the Griffith threshold, and close to the strain of uniform breakdown.
      Contrary to the case of perfectly harmonic behavior up to the fracture point, in
      the piecewise linear elastic model the crack velocity is lower than the sound
      velocity, reaching this limiting value at the strain of uniform breakdown. We
      complement the analytical results with numerical simulations and find excellent
      agreement.

PMID- 16907151
TI  - Clustering algorithm for determining community structure in large networks.
AB  - We propose an algorithm to find the community structure in complex networks based
      on the combination of spectral analysis and modularity optimization. The
      clustering produced by our algorithm is as accurate as the best algorithms on the
      literature of modularity optimization; however, the main asset of the algorithm
      is its efficiency. The best match for our algorithm is Newman's fast algorithm,
      which is the reference algorithm for clustering in large networks due to its
      efficiency. When both algorithms are compared, our algorithm outperforms the fast
      algorithm both in efficiency and accuracy of the clustering, in terms of
      modularity. Thus, the results suggest that the proposed algorithm is a good
      choice to analyze the community structure of medium and large networks in the
      range of tens and hundreds of thousand vertices.

PMID- 16907152
TI  - Modeling self-organization of communication and topology in social networks.
AB  - This paper introduces a model of self-organization between communication and
      topology in social networks, with a feedback between different communication
      habits and the topology. To study this feedback, we let agents communicate to
      build a perception of a network and use this information to create strategic
      links. We observe a narrow distribution of links when the communication is low
      and a system with a broad distribution of links when the communication is high.
      We also analyze the outcome of chatting, cheating, and lying, as strategies to
      get better access to information in the network. Chatting, although only adopted
      by a few agents, gives a global gain in the system. Contrary, a global loss is
      inevitable in a system with too many liars.

PMID- 16907153
TI  - Short-time dynamics of a family of XY noncollinear magnets.
AB  - Critical scaling and universality in the short-time dynamics for
      antiferromagnetic models on a three-dimensional stacked triangular lattice are
      investigated using Monte Carlo simulation. We have determined the critical point
      by searching for the best power law for the order parameter as a function of time
      and measured the critical exponents. Our results indicate that it is possible to
      distinguish weak first-order from second-order phase transitions and confirm that
      XY antiferromagnetic systems undergo a (weak) first-order phase transition
      accompanied by pseudocritical scaling.

PMID- 16907154
TI  - Statistical mechanics of community detection.
AB  - Starting from a general ansatz, we show how community detection can be
      interpreted as finding the ground state of an infinite range spin glass. Our
      approach applies to weighted and directed networks alike. It contains the ad hoc
      introduced quality function from [J. Reichardt and S. Bornholdt, Phys. Rev. Lett.
      93, 218701 (2004)] and the modularity Q as defined by Newman and Girvan [Phys.
      Rev. E 69, 026113 (2004)] as special cases. The community structure of the
      network is interpreted as the spin configuration that minimizes the energy of the
      spin glass with the spin states being the community indices. We elucidate the
      properties of the ground state configuration to give a concise definition of
      communities as cohesive subgroups in networks that is adaptive to the specific
      class of network under study. Further, we show how hierarchies and overlap in the
      community structure can be detected. Computationally efficient local update rules
      for optimization procedures to find the ground state are given. We show how the
      ansatz may be used to discover the community around a given node without
      detecting all communities in the full network and we give benchmarks for the
      performance of this extension. Finally, we give expectation values for the
      modularity of random graphs, which can be used in the assessment of statistical
      significance of community structure.

PMID- 16907155
TI  - Direct determination of liquid phase coexistence by Monte Carlo simulations.
AB  - A formalism to determine coexistence points by means of Monte Carlo simulations
      is presented. The general idea of the method is to perform a simulation
      simultaneously in several unconnected boxes which can exchange particles. At
      equilibrium, most of the boxes will be occupied by a homogeneous phase. The
      compositions of these boxes yield coexisting points on the binodal. However,
      since the overall composition is fixed, at least one of the boxes will contain an
      interface. We show that this does not affect the results, provided that the
      interface has no net curvature. We coin the name "Helmholtz-ensemble method,"
      because the method is related to the well-known Gibbs-ensemble method, but the
      volume of the boxes is constant. Since the box volumes are constant, we expect
      that this method will be particularly useful for lattice models. The accuracy of
      the Helmholtz-ensemble method is benchmarked against known coexistence curves of
      the three-dimensional Ising model with excellent results.

PMID- 16907156
TI  - Topology regulates the distribution pattern of excitations in excitable dynamics
      on graphs.
AB  - We study the average excitation density in a simple model of excitable dynamics
      on graphs and find that this density strongly depends on certain topological
      features of the graph, namely connectivity and degree correlations, but to a
      lesser extent on the degree distribution. Remarkably, the average excitation
      density is changed via the distribution pattern of excitations: An increase in
      connectivity induces a transition from globally to locally organized excitations
      and, as a result, leads to an increase in the excitation density. A similar
      transition can be induced by increasing the rate of spontaneous excitations while
      keeping the graph architecture constant.

PMID- 16907157
TI  - Emergence of scale-free networks from local connectivity and communication trade
      offs.
AB  - We suggest a mechanism of connectivity evolution in networks to account for the
      emergence of scale-free behavior. The mechanism works on a fixed set of nodes and
      promotes growth from a minimally connected initial topology by the addition of
      edges. A new edge is added between two nodes depending on the trade-off between a
      gain and a cost function of local connectivity and communication properties. We
      report on simulation results that indicate the appearance of power-law
      distributions of node degrees for selected parameter combinations.

PMID- 16907158
TI  - Heat conduction in a confined solid strip: response to external strain.
AB  - We study heat conduction in a system of hard disks confined to a narrow two
      dimensional channel. The system is initially in a high-density solidlike phase.
      We study, through nonequilibrium molecular dynamics simulations, the dependence
      of the heat current on an externally applied elongational strain. The strain
      leads to deformation and failure of the solid and we find that the changes in
      internal structure can lead to very sharp changes in the heat current. A simple
      free-volume-type calculation of the heat current in a finite hard-disk system is
      proposed. This reproduces some qualitative features of the current-strain graph
      for small strains.

PMID- 16907159
TI  - Wikipedias: collaborative web-based encyclopedias as complex networks.
AB  - Wikipedia is a popular web-based encyclopedia edited freely and collaboratively
      by its users. In this paper we present an analysis of Wikipedias in several
      languages as complex networks. The hyperlinks pointing from one Wikipedia article
      to another are treated as directed links while the articles represent the nodes
      of the network. We show that many network characteristics are common to different
      language versions of Wikipedia, such as their degree distributions, growth,
      topology, reciprocity, clustering, assortativity, path lengths, and triad
      significance profiles. These regularities, found in the ensemble of Wikipedias in
      different languages and of different sizes, point to the existence of a unique
      growth process. We also compare Wikipedias to other previously studied networks.

PMID- 16907160
TI  - Self-organization with equilibration: a model for the intermediate phase in
      rigidity percolation.
AB  - Recent experimental results for covalent glasses suggest the existence of an
      intermediate phase attributed to the self-organization of the glass network
      resulting from the tendency to minimize its internal stress. However, the exact
      nature of this experimentally measured phase remains unclear. We modified a
      previously proposed model of self-organization by generating a uniform sampling
      of stress-free networks. In our model, studied on a diluted triangular lattice,
      an unusual intermediate phase appears, in which both rigid and floppy networks
      have a chance to occur, a result also observed in a related model on a Bethe
      lattice by Barre et al[Phys. Rev. Lett. 94, 208701 (2005)]. Our results for the
      bond-configurational entropy of self-organized networks, which turns out to be
      only about 2% lower than that of random networks, suggest that a self-organized
      intermediate phase could be common in systems near the rigidity percolation
      threshold.

PMID- 16907161
TI  - Optimal design of spatial distribution networks.
AB  - We consider the problem of constructing facilities such as hospitals, airports,
      or malls in a country with a nonuniform population density, such that the average
      distance from a person's home to the nearest facility is minimized. We review
      some previous approximate treatments of this problem that indicate that the
      optimal distribution of facilities should have a density that increases with
      population density, but does so slower than linearly, as the two-thirds power. We
      confirm this result numerically for the particular case of the United States with
      recent population data using two independent methods, one a straightforward
      regression analysis, the other based on density-dependent map projections. We
      also consider strategies for linking the facilities to form a spatial network,
      such as a network of flights between airports, so that the combined cost of
      maintenance of and travel on the network is minimized. We show specific examples
      of such optimal networks for the case of the United States.

PMID- 16907162
TI  - Amorphous systems in athermal, quasistatic shear.
AB  - We present results on a series of two-dimensional atomistic computer simulations
      of amorphous systems subjected to simple shear in the athermal, quasistatic
      limit. The athermal quasistatic trajectories are shown to separate into smooth,
      reversible elastic branches which are intermittently broken by discrete
      catastrophic plastic events. The onset of a typical plastic event is studied with
      precision, and it is shown that the mode of the system which is responsible for
      the loss of stability has structure in real space which is consistent with a
      quadrupolar source acting on an elastic matrix. The plastic events themselves are
      shown to be composed of localized shear transformations which organize into lines
      of slip which span the length of the simulation cell, and a mechanism for the
      organization is discussed. Although within a single event there are strong
      spatial correlations in the deformation, we find little correlation from one
      event to the next, and these transient lines of slip are not to be confounded
      with the persistent regions of localized shear--so-called "shear bands"--found in
      related studies. The slip lines give rise to particular scalings with system
      length of various measures of event size. Strikingly, data obtained using three
      differing interaction potentials can be brought into quantitative agreement after
      a simple rescaling, emphasizing the insensitivity of the emergent plastic
      behavior in these disordered systems to the precise details of the underlying
      interactions. The results should be relevant to understanding plastic deformation
      in systems such as metallic glasses well below their glass temperature, soft
      glassy systems (such as dense emulsions), or compressed granular materials.

PMID- 16907163
TI  - Fluctuation-induced instabilities in front propagation up a comoving reaction
      gradient in two dimensions.
AB  - We study two-dimensional (2D) fronts propagating up a comoving reaction rate
      gradient in finite number reaction-diffusion systems. We show that in a 2D
      rectangular channel, planar solutions to the deterministic mean-field equation
      are stable with respect to deviations from planarity. We argue that planar fronts
      in the corresponding stochastic system, on the other hand, are unstable if the
      channel width exceeds a critical value. Furthermore, the velocity of the
      stochastic fronts is shown to depend on the channel width in a simple and
      interesting way, in contrast to fronts in the deterministic mean-field equation.
      Thus fluctuations alter the behavior of these fronts in an essential way. These
      effects are shown to be partially captured by introducing a density cutoff in the
      reaction rate. Moreover, some of the predictions of the cutoff mean-field
      approach are shown to be in quantitative accord with the stochastic results.

PMID- 16907164
TI  - Eliminated corrections to scaling around a renormalization-group fixed point:
      transfer-matrix simulation of an extended d=3 Ising model.
AB  - Extending the parameter space of the three-dimensional (d=3) Ising model, we
      search for a regime of eliminated corrections to finite-size scaling. For that
      purpose, we consider a real-space renormalization group (RSRG) with respect to a
      couple of clusters simulated with the transfer-matrix (TM) method. Imposing a
      criterion of "scale invariance," we determine a location of the nontrivial RSRG
      fixed point. Subsequent large-scale TM simulation around the fixed point reveals
      eliminated corrections to finite-size scaling. As anticipated, such an
      elimination of corrections admits systematic finite-size-scaling analysis. We
      obtained the estimates for the critical indices as nu=0.6245(28) and
      y(h)=2.4709(73). As demonstrated, with the aid of the preliminary RSRG survey,
      the transfer-matrix simulation provides rather reliable information on
      criticality even for d=3, where the tractable system size is restricted severely.

PMID- 16907165
TI  - Network analysis of online bidding activity.
AB  - With the advent of digital media, people are increasingly resorting to online
      channels for commercial transactions. The online auction is a prototypical
      example. In such online transactions, the pattern of bidding activity is more
      complex than traditional offline transactions; this is because the number of
      bidders participating in a given transaction is not bounded and the bidders can
      also easily respond to the bidding instantaneously. By using the recently
      developed network theory, we study the interaction patterns between bidders
      (items) who (that) are connected when they bid for the same item (if the item is
      bid by the same bidder). The resulting network is analyzed by using the
      hierarchical clustering algorithm, which is used for clustering analysis for
      expression data from DNA microarrays. A dendrogram is constructed for the item
      subcategories; this dendrogram is compared to a traditional classification
      scheme. The implication of the difference between the two is discussed.

PMID- 16907166
TI  - Crossover behavior in failure avalanches.
AB  - Composite materials, with statistically distributed thresholds for breakdown of
      individual elements, are considered. During the failure process of such materials
      under external stress (load or voltage), avalanches consisting of simultaneous
      rupture of several elements occur, with a distribution D(Delta) of the magnitude
      Delta of such avalanches. The distribution is typically a power law D(Delta)
      proportional to Delta (-xi). For the systems we study here, a crossover behavior
      is seen between two power laws, with a small exponent xi in the vicinity of
      complete breakdown and a larger exponent xi for failures away from the breakdown
      point. We demonstrate this analytically for bundles of many fibers where the load
      is uniformly distributed among the surviving fibers. In this case xi=3/2 near the
      breakdown point and xi=5/2 away from it. The latter is known to be the generic
      behavior. This crossover is a signal of imminent catastrophic failure of the
      material. Near the breakdown point, avalanche statistics show nontrivial finite
      size scaling. We observe similar crossover behavior in a network of electric
      fuses, and find xi=2 near the catastrophic failure and xi=3 away from it. For
      this fuse model power dissipation avalanches show a similar crossover near
      breakdown.

PMID- 16907167
TI  - Understanding widely scattered traffic flows, the capacity drop, and platoons as
      effects of variance-driven time gaps.
AB  - We investigate the adaptation of the time headways in car-following models as a
      function of the local velocity variance, which is a measure of the inhomogeneity
      of traffic flow. We apply this mechanism to several car-following models and
      simulate traffic breakdowns in open systems with an on-ramp as bottleneck and in
      a closed ring road. Single-vehicle data and one-minute aggregated data generated
      by several virtual detectors show a semiquantitative agreement with microscopic
      and flow-density data from the Dutch freeway A9. This includes the observed
      distributions of the net time headways for free and congested traffic, the
      velocity variance as a function of density, and the fundamental diagram. The
      modal value of the time headway distribution is shifted by a factor of about 2
      under congested conditions. Macroscopically, this corresponds to the capacity
      drop at the transition from free to congested traffic. The simulated fundamental
      diagram shows free, synchronized, and jammed traffic, and a wide scattering in
      the congested traffic regime. We explain this by a self-organized variance-driven
      process that leads to the spontaneous formation and decay of long-lived platoons
      even for a deterministic dynamics on a single lane.

PMID- 16907168
TI  - Understanding the evolution dynamics of internet topology.
AB  - The internet structure is extremely complex. The positive-feedback preference
      (PFP) model is a recently introduced internet topology generator. The model uses
      two generic algorithms to replicate the evolution dynamics observed on the
      internet historic data. The phenomenological model was originally designed to
      match only two topology properties of the internet, i.e., the rich-club
      connectivity and the exact form of degree distribution, whereas numerical
      evaluation has shown that the PFP model accurately reproduces a large set of
      other nontrivial characteristics as well. This paper aims to investigate why and
      how this generative model captures so many diverse properties of the internet.
      Based on comprehensive simulation results, the paper presents a detailed analysis
      on the exact origin of each of the topology properties produced by the model.
      This work reveals how network evolution mechanisms control the obtained topology
      properties and it also provides insights on correlations between various
      structural characteristics of complex networks.

PMID- 16907169
TI  - Optimization of the robustness of multimodal networks.
AB  - We investigate the robustness against both random and targeted node removal of
      networks in which P(k), the distribution of nodes with degree k, is a multimodal
      distribution, [formula--see text] with k(i) proportional to b -(i-1) and Dirac's
      delta function delta (x). We refer to this type of network as a scale-free
      multimodal network. For m=2, the network is a bimodal network; in the limit m
      approaches infinity, the network models a scale-free network. We calculate and
      optimize the robustness for given values of the number of modes m, the total
      number of nodes N, and the average degree <k>, using analytical formulas for the
      random and targeted node removal thresholds for network collapse. We find, when
      N>>1, that (i) the robustness against random and targeted node removal for this
      multimodal network is controlled by a single combination of variables, N(1/m-1),
      (ii) the robustness of the multimodal network against targeted node removal
      decreases rapidly when the number of modes becomes larger than a critical value
      that is of the order of 1n N, and (iii) the values of exponent lambda(opt) that
      characterizes the scale-free degree distribution of the multimodal network that
      maximize the robustness against both random and targeted node removal fall
      between 2.5 and 3.

PMID- 16907170
TI  - Network of epicenters of the Olami-Feder-Christensen model of earthquakes.
AB  - We study the dynamics of the Olami-Feder-Christensen (OFC) model of earthquakes,
      focusing on the behavior of sequences of epicenters regarded as a growing complex
      network. Besides making a detailed and quantitative study of the effects of the
      borders (the occurrence of epicenters is dominated by a strong border effect
      which does not scale with system size), we examine the degree distribution and
      the degree correlation of the graph. We detect sharp differences between the
      conservative and nonconservative regimes of the model. Removing border effects,
      the conservative regime exhibits a Poisson-like degree statistics and is
      uncorrelated, while the nonconservative has a broad power-law-like distribution
      of degrees (if the smallest events are ignored), which reproduces the observed
      behavior of real earthquakes. In this regime the graph has also an unusually
      strong degree correlation among the vertices with higher degree, which is the
      result of the existence of temporary attractors for the dynamics: as the system
      evolves, the epicenters concentrate increasingly on fewer sites, exhibiting
      strong synchronization, but eventually spread again over the lattice after a
      series of sufficiently large earthquakes. We propose an analytical description of
      the dynamics of this growing network, considering a Markov process network with
      hidden variables, which is able to account for the mentioned properties.

PMID- 16907171
TI  - Bound states in elastic waveguides.
AB  - We consider numerically the L-, T-, and X-shaped elastic waveguides with the
      Dirichlet boundary conditions for in-plane deformations (displacements) which
      obey the vectorial Navier-Cauchy equation. In the X-shaped waveguide we show the
      existence of a doubly degenerate bound state with frequency below the first
      symmetrical cutoff frequency, which belongs to the two-dimensional irreducible
      representation E of symmetry group C(4upsilon). Moreover the next bound state is
      below the next antisymmetric cutoff frequency. This bound state belongs to the
      irreducible representation A2. The T-shaped waveguide has only one bound state
      while the L-shaped one has no bound states.

PMID- 16907172
TI  - Phase control of intermittency in dynamical systems.
AB  - We present a nonfeedback method to tame or enhance crisis-induced intermittency
      in dynamical systems. By adding a small harmonic perturbation to a parameter of
      the system, the intermittent behavior can be suppressed or enhanced depending on
      the value of the phase difference between the main driving and the perturbation.
      The validity of the method is shown both in the model and in an experiment with a
      CO2 laser. An analysis of this scheme applied to the quadratic map near crisis
      illustrates the role of phase control in nonlinear dynamical systems.

PMID- 16907173
TI  - Characterization of noise-induced strange nonchaotic attractors.
AB  - Strange nonchaotic attractors (SNAs) were previously thought to arise exclusively
      in quasiperiodic dynamical systems. A recent study has revealed, however, that
      such attractors can be induced by noise in nonquasiperiodic discrete-time maps or
      in periodically driven flows. In particular, in a periodic window of such a
      system where a periodic attractor coexists with a chaotic saddle (nonattracting
      chaotic invariant set), none of the Lyapunov exponents of the asymptotic
      attractor is positive. Small random noise is incapable of causing characteristic
      changes in the Lyapunov spectrum, but it can make the attractor geometrically
      strange by dynamically connecting the original periodic attractor with the
      chaotic saddle. Here we present a detailed study of noise-induced SNAs and the
      characterization of their properties. Numerical calculations reveal that the
      fractal dimensions of noise-induced SNAs typically assume fractional values, in
      contrast to SNAs in quasiperiodically driven systems whose dimensions are
      integers. An interesting finding is that the fluctuations of the finite-time
      Lyapunov exponents away from their asymptotic values obey an exponential
      distribution, the generality of which we are able to establish by a theoretical
      analysis using random matrices. We suggest a possible experimental test. We
      expect noise-induced SNAs to be general.

PMID- 16907174
TI  - Wave packet autocorrelation functions for quantum hard-disk and hard-sphere
      billiards in the high-energy, diffraction regime.
AB  - We consider the time evolution of a wave packet representing a quantum particle
      moving in a geometrically open billiard that consists of a number of fixed hard
      disk or hard-sphere scatterers. Using the technique of multiple collision
      expansions we provide a first-principle analytical calculation of the time
      dependent autocorrelation function for the wave packet in the high-energy
      diffraction regime, in which the particle's de Broglie wavelength, while being
      small compared to the size of the scatterers, is large enough to prevent the
      formation of geometric shadow over distances of the order of the particle's free
      flight path. The hard-disk or hard-sphere scattering system must be sufficiently
      dilute in order for this high-energy diffraction regime to be achievable. Apart
      from the overall exponential decay, the autocorrelation function exhibits a
      generally complicated sequence of relatively strong peaks corresponding to
      partial revivals of the wave packet. Both the exponential decay (or escape) rate
      and the revival peak structure are predominantly determined by the underlying
      classical dynamics. A relation between the escape rate, and the Lyapunov
      exponents and Kolmogorov-Sinai entropy of the counterpart classical system,
      previously known for hard-disk billiards, is strengthened by generalization to
      three spatial dimensions. The results of the quantum mechanical calculation of
      the time-dependent autocorrelation function agree with predictions of the
      semiclassical periodic orbit theory.

PMID- 16907175
TI  - Creating bound states in excitable media by means of nonlocal coupling.
AB  - We consider pulses of excitation in reaction-diffusion systems subjected to
      nonlocal coupling. This coupling represents long-range connections between the
      elements of the medium; the connection strength decays exponentially with the
      distance. Without coupling, pulses interact only repulsively and bound states
      with two or more pulses propagating at the same velocity are impossible. Upon
      switching on nonlocal coupling, pulses begin to interact attractively and form
      bound states. First we present numerical results on the emergence of bound states
      in the excitable Oregonator model for the photosensitive Belousov-Zhabotinsky
      reaction with nonlocal coupling. Then we show that the appearance of bound states
      is provided solely by the exponential decay of nonlocal coupling and thus can be
      found in a wide class of excitable systems, regardless of the particular
      kinetics. The theoretical explanation of the emergence of bound states is based
      on the bifurcation analysis of the profile equations that describe the spatial
      shape of pulses. The central object is a codimension-4 homoclinic orbit which
      exists for zero coupling strength. The emergence of bound states is described by
      the bifurcation to 2-homoclinic solutions from the codimension-4 homoclinic orbit
      upon switching on nonlocal coupling. We stress that the high codimension of the
      bifurcation to bound states is generic, provided that the coupling range is
      sufficiently large.

PMID- 16907176
TI  - Traveling ion channel density waves affected by a conservation law.
AB  - A model of mobile, charged ion channels embedded in a biomembrane is
      investigated. The ion channels fluctuate between an opened and a closed state
      according to a simple two-state reaction scheme whereas the total number of ion
      channels is a conserved quantity. Local transport mechanisms suggest that the ion
      channel densities are governed by electrodiffusionlike equations that have to be
      supplemented by a cable-type equation describing the dynamics of the
      transmembrane voltage. It is shown that the homogeneous distribution of ion
      channels may become unstable to either a stationary or an oscillatory
      instability. The nonlinear behavior immediately above threshold of an oscillatory
      bifurcation occurring at finite wave number is analyzed in terms of amplitude
      equations. Due to the conservation law imposed on ion channels, large-scale modes
      couple to the finite-wave-number instability and have thus to be included in the
      asymptotic analysis near the onset of pattern formation. A modified Ginzburg
      Landau equation extended by long-wavelength stationary excitations is
      established, and it is highlighted how the global conservation law affects the
      stability of traveling ion channel density waves.

PMID- 16907177
TI  - Dynamics of bound states of same-chirality spiral waves.
AB  - We describe the dynamics of bound states of same-chirality spirals in a generic
      numerical model of an excitable medium. For each bound state, we analyze its tip
      trajectory patterns and determine its characteristic frequencies. We report two
      previously unidentified bound states: for spiral pairs, a state that exhibits
      alternating cycles of small and large distances between collisions (A2); for
      triplets, the first example of a meandering bound state (M3). In parameter space,
      A2 lies in between the previously described oscillating pairs (O2) and master
      slave pairs (MS). We present numerical evidence that the transition O2-->A2
      occurs via a supercritical period-doubling bifurcation, while the transition A2-
      >MS occurs via a symmetry breaking secondary Hopf bifurcation. A classification
      of all regimes according to dynamical systems theory exposes the wealth of
      phenomena exhibited by multiarmed spiral waves.

PMID- 16907178
TI  - Stabilization from chaotic to periodical states in a model of cellular automaton
      for oxidation of CO.
AB  - The chaotic behavior of a chemical reaction can be controlled perturbing
      periodically some of the parameters externally governing the reaction. Based on
      the resonance phenomenon, the method of external forcing can convert chaotic
      behavior into a periodical one through the application of a sinusoidal
      modulation. In this paper we analyze the effect of a periodical perturbation on
      room temperature in a model of cellular automaton that studies catalytic
      oxidation of CO. This model considers the reaction of carbon monoxide and oxygen
      adsorbed on a surface allowing the variation of the surface temperature and
      analyzing the time oscillations in the reaction. The results of simulations of
      this model show quasiperiodical and chaotic behaviors. Then the strategy of
      control through periodical forcing is able to remove the chaotic dynamics by
      means of the stabilization of periodical solutions, there being enough of a
      perturbing harmonic function with only one frequency to transform a chaotic state
      of the system into a periodical state with periodicity 1.

PMID- 16907179
TI  - Characterization of the domain chaos convection state by the largest Lyapunov
      exponent.
AB  - Using numerical integrations of the Boussinesq equations in rotating cylindrical
      domains with realistic boundary conditions, we have computed the value of the
      largest Lyapunov exponent lambda1 for a variety of aspect ratios and driving
      strengths. We study in particular the domain chaos state, which bifurcates
      supercritically from the conducting fluid state and involves extended propagating
      fronts as well as point defects. We compare our results with those from Egolf,
      [Nature 404, 733 (2000)], who suggested that the value of lambda1 for the spiral
      defect chaos state of a convecting fluid was determined primarily by bursts of
      instability arising from short-lived, spatially localized dislocation nucleation
      events. We also show that the quantity lambda1 is not intensive for aspect ratios
      Gamma over the range 20<Gamma<40 and that the scaling exponent of lambda1 near
      onset is consistent with the value predicted by the amplitude equation formalism.

PMID- 16907180
TI  - Spatiotemporal intermittency and scaling laws in the coupled sine circle map
      lattice.
AB  - We study spatiotemporal intermittency (STI) in a system of coupled sine circle
      maps. The phase diagram of the system shows parameter regimes with STI of both
      the directed percolation (DP) and non-DP class. STI with synchronized laminar
      behavior belongs to the DP class. The regimes of non-DP behavior show spatial
      intermittency (SI), where the temporal behavior of both the laminar and burst
      regions is regular, and the distribution of laminar lengths scales as a power
      law. The regular temporal behavior for the bursts seen in these regimes of
      spatial intermittency can be periodic or quasiperiodic, but the laminar length
      distributions scale with the same power law, which is distinct from the DP case.
      STI with traveling wave laminar states also appears in the phase diagram.
      Solitonlike structures appear in this regime. These are responsible for
      crossovers with accompanying nonuniversal exponents. The soliton lifetime
      distributions show power-law scaling in regimes of long average soliton
      lifetimes, but peak at characteristic scales with a power-law tail in regimes of
      short average soliton lifetimes. The signatures of each type of intermittent
      behavior can be found in the dynamical characterizers of the system viz. the
      eigenvalues of the stability matrix. We discuss the implications of our results
      for behavior seen in other systems which exhibit spatiotemporal intermittency.

PMID- 16907181
TI  - Synchronization of unidirectionally coupled Mackey-Glass analog circuits with
      frequency bandwidth limitations.
AB  - Synchronization of chaotic systems has been studied extensively, and especially,
      the possible applications to the communication systems motivated many research
      areas. We demonstrate the effect of the frequency bandwidth limitations in the
      communication channel on the synchronization of two unidirectionally coupled
      Mackey-Glass (MG) analog circuits, both numerically and experimentally. MG system
      is known to generate high dimensional chaotic signals. The chaotic signal
      generated from the drive MG system is modified by a low pass filter and is then
      transmitted to the response MG system. Our results show that the inclusion of the
      dominant frequency component of the original drive signals is crucial to achieve
      synchronization between the drive and response circuits. The maximum cross
      correlation and the corresponding time shift reveal that the frequency-dependent
      coupling introduced by the low pass filtering effect in the communication channel
      change the quality of synchronization.

PMID- 16907182
TI  - Directed transport and Floquet analysis for a periodically kicked wave packet at
      a quantum resonance.
AB  - The dynamics of a kicked quantum mechanical wave packet at a quantum resonance is
      studied in the framework of Floquet analysis. It is seen how a directed current
      can be created out of a homogeneous initial state at certain resonances in an
      asymmetric potential. The almost periodic parameter dependence of the current is
      found to be connected with level crossings in the Floquet spectrum.

PMID- 16907183
TI  - Optimized suppression of coherent noise from seismic data using the Karhunen
      Loeve transform.
AB  - Signals obtained in land seismic surveys are usually contaminated with coherent
      noise, among which the ground roll (Rayleigh surface waves) is of major concern
      for it can severely degrade the quality of the information obtained from the
      seismic record. This paper presents an optimized filter based on the Karhunen
      Loeve transform for processing seismic images contaminated with ground roll. In
      this method, the contaminated region of the seismic record, to be processed by
      the filter, is selected in such way as to correspond to the maximum of a properly
      defined coherence index. The main advantages of the method are that the ground
      roll is suppressed with negligible distortion of the remnant reflection signals
      and that the filtering procedure can be automated. The image processing technique
      described in this study should also be relevant for other applications where
      coherent structures embedded in a complex spatiotemporal pattern need to be
      identified in a more refined way. In particular, it is argued that the method is
      appropriate for processing optical coherence tomography images whose quality is
      often degraded by coherent noise (speckle).

PMID- 16907184
TI  - Delayed feedback control of noise-induced patterns in excitable media.
AB  - We show that characteristic features of noise-induced spatiotemporal patterns in
      excitable media can be effectively controlled by applying delayed feedback.
      Actually, by variation of the time delay and of the strength of the feedback one
      can deliberately change both spatial and temporal coherence, as well as adjust
      the characteristic time scales.

PMID- 16907185
TI  - Correlation between non-Gaussian statistics of a scalar and its dissipation rate
      in turbulent flows.
AB  - This paper reports an experimental study on the correlation between the deviation
      from Gaussianity of the probability density function (PDF) of a fluctuating
      scalar and the dependence of the scalar dissipation on the scalar itself in
      turbulent flows. The study demonstrates that the departure of the scalar PDF from
      Gaussianity reflects the degree to which the dissipation rate depends
      statistically on the scalar. Of important significance, present results obtained
      from wake and jet flows, together with those deduced from previous work on
      various turbulent flows, appear to point to a generic expression for the total
      correlation. This expression suggests that the analytical result of O'Brien and
      Jiang [Phys. Fluids A 3, 3121 (1991)], derived for homogeneous turbulence, should
      be also valid for inhomogeneous turbulence. That is, the statistical independence
      of the scalar dissipation and the scalar itself appears to act as the sufficient
      and necessary condition for the scalar PDF to be Gaussian in any stationary
      turbulence. It follows that the independence assumption, often used in combustion
      modeling, is reasonable only in the flow region where the scalar PDF is closely
      Gaussian.

PMID- 16907186
TI  - NMR velocity mapping of gas flow around solid objects.
AB  - We present experimental visualizations of gas flow around solid blunt bodies by
      NMR imaging. NMR velocimetry is a model-free and tracer-free experimental means
      for quantitative and multi-dimensional flow visualization. Hyperpolarization of
      (129)Xe provided sufficient NMR signal to overcome the low density of the dilute
      gas phase, and its long coherence time allows for true velocity vector mapping.
      In this study, the diverging gas flow around and wake patterns immediately behind
      a sphere could be vectorally visualized and quantified. In a similar experiment,
      the flow over an aerodynamic model airplane body revealed a less disrupted flow
      pattern.

PMID- 16907187
TI  - Large-scale flow effects, energy transfer, and self-similarity on turbulence.
AB  - The effect of large scales on the statistics and dynamics of turbulent
      fluctuations is studied using data from high resolution direct numerical
      simulations. Three different kinds of forcing, and spatial resolutions ranging
      from 256(3) to 1024(3), are being used. The study is carried out by investigating
      the nonlinear triadic interactions in Fourier space, transfer functions,
      structure functions, and probability density functions. Our results show that the
      large scale flow plays an important role in the development and the statistical
      properties of the small scale turbulence. The role of helicity is also
      investigated. We discuss the link between these findings and intermittency,
      deviations from universality, and possible origins of the bottleneck effect.
      Finally, we briefly describe the consequences of our results for the subgrid
      modeling of turbulent flows.

PMID- 16907188
TI  - Backwards and forwards relative dispersion in turbulent flow: an experimental
      investigation.
AB  - From particle tracking velocimetry we present an experimental measure of the
      ratio between backwards and forwards relative dispersion in an intermediate
      Reynolds number turbulent flow. Lack of time-reversal symmetry implies that their
      ratio may be different from 1. From a stochastic model, this has recently been
      studied by Sawford et al [Phys. Fluids 17, 095109 (2005)] giving ratios between 5
      and 20. We find a value of approximately 2 and discuss it in the context of the
      characteristics of the rate of strain tensor s(ij). An analysis of a direct
      numerical simulation by Biferale et al [Phys. Rev. Lett. 93, 064502 (2004) and
      Phys. Fluids 17, 021701 (2004)] gives the same result.

PMID- 16907189
TI  - Renormalization of tracer turbulence leading to fractional differential
      equations.
AB  - For many years quasilinear renormalization has been applied to numerous problems
      in turbulent transport. This scheme relies on the localization hypothesis to
      derive a linear transport equation from a simplified stochastic description of
      the underlying microscopic dynamics. However, use of the localization hypothesis
      narrows the range of transport behaviors that can be captured by the renormalized
      equations. In this paper, we construct a renormalization procedure that manages
      to avoid the localization hypothesis completely and produces renormalized
      transport equations, expressed in terms of fractional differential operators,
      that exhibit much more of the transport phenomenology observed in nature. This
      technique provides a first step toward establishing a rigorous link between the
      microscopic physics of turbulence and the fractional transport models proposed
      phenomenologically for a wide variety of turbulent systems such as neutral fluids
      or plasmas.

PMID- 16907190
TI  - Nonlocal modulation of the energy cascade in broadband-forced turbulence.
AB  - Classically, large-scale forced turbulence is characterized by a transfer of
      energy from large to small scales via nonlinear interactions. We have
      investigated the changes in this energy transfer process in broadband forced
      turbulence where an additional perturbation of flow at smaller scales is
      introduced. The modulation of the energy dynamics via the introduction of forcing
      at smaller scales occurs not only in the forced region but also in a broad range
      of length scales outside the forced bands due to nonlocal triad interactions.
      Broadband forcing changes the energy distribution and energy transfer function in
      a characteristic manner leading to a significant modulation of the turbulence. We
      studied the changes in this transfer of energy when changing the strength and
      location of the small-scale forcing support. The energy content in the larger
      scales was observed to decrease, while the energy transport power for scales in
      between the large and small scale forcing regions was enhanced. This was
      investigated further in terms of the detailed transfer function between the triad
      contributions and observing the long-time statistics of the flow. The energy is
      transferred toward smaller scales not only by wave numbers of similar size as in
      the case of large-scale forced turbulence, but by a much wider extent of scales
      that can be externally controlled.

PMID- 16907191
TI  - Reaction enhancement of point sources due to vortex stirring.
AB  - We investigate a class of reactive advection-diffusion problems motivated by an
      ecological mixing process. We use analytical and numerical methods to determine
      reaction rates between two initially distinct scalar point masses that are
      separated from one another by a third (nonreactive) scalar. The scalars are
      stirred by a single two-dimensional vortex in a variety of geometrical
      configurations. We show that the aggregate second-order reaction rate in the low
      concentration limit is enhanced by the instantaneous stirring processes, relative
      to the rate predicted by an equivalent eddy diffusivity. The peak reaction rate
      grows as P(1/3), and the time to reach the peak decreases as P(-2/3), where P is
      the Peclet number. The results of this study have important implications not only
      for ecological modeling, but for the general understanding of turbulent reactive
      flows.

PMID- 16907192
TI  - Dynamical behavior of the motions associated with the nonlinear periodic regime
      in a laboratory plasma subject to delayed feedback.
AB  - Time-delayed feedback is applied to the motions associated with the nonlinear
      periodic regime generated due to current-driven ion acoustic instability; this is
      a typical instability in a laboratory plasma, and the dynamical behavior is
      experimentally investigated using delayed feedback. A time-delayed
      autosynchronization method is applied. When delayed feedback is applied to the
      nonlinear periodic orbit, the periodic state changes to various motions depending
      on the control parameters, namely, the arbitrary time delay and the
      proportionality constant. Lyapunov exponents are calculated in order to examine
      the dynamical behavior.

PMID- 16907193
TI  - Transition of absolute instability from global to local modes in a gyrotron
      traveling-wave amplifier.
AB  - The gyrotron traveling-wave amplifier employing the distributed-loss scheme is
      capable of very high gain and effective in suppressing the global absolute
      instabilities. This study systematically characterizes the local absolute
      instabilities and their transitional behavior. The local absolute instabilities
      are analyzed using a model that incorporates the penetration of the field from
      the copper section into the lossy section. The axial modes were characterized
      from the perspective of beam-wave interaction and were found to share many
      characteristics with the global modes. The transition from global modes to local
      modes as the distributed loss increases was demonstrated. The electron transit
      angle in the copper section, which determines the feedback criterion, governs the
      survivability of an oscillation. In addition, the oscillation thresholds
      predicted using this model are more accurate than those obtained using a
      simplified model.

PMID- 16907194
TI  - Angular distribution of neutrons from deuterated cluster explosions driven by
      femtosecond laser pulses.
AB  - We have studied experimentally the angular distributions of fusion neutrons from
      plasmas of multi-keV ion temperature, created by 40 fs, multi-TW laser pulses in
      dense plumes of D2 and CD4 clusters. A slight anisotropy in the neutron emission
      is observed. We attribute this anisotropy to the fact that the differential cross
      section for DD fusion is anisotropic even at low collision energies, and this,
      coupled with the geometry of the gas jet target, leads to beam-target neutrons
      that are slightly directed. The qualitative features of this anisotropy are
      confirmed by Monte Carlo simulations.

PMID- 16907195
TI  - Prediction and observation of tin and silver plasmas with index of refraction
      greater than one in the soft x-ray range.
AB  - We present the calculated prediction and the experimental confirmation that
      doubly ionized Ag and Sn plasmas can have an index of refraction greater than one
      for soft x-ray wavelengths. Interferometry experiments conducted using a
      capillary discharge soft x-ray laser operating at a wavelength of confirm that in
      few times ionized laser-created plasmas of these elements the anomalous
      dispersion from bound electrons can dominate the free electron contribution,
      making the index of refraction greater than one. The results confirm that bound
      electrons can strongly influence the index of refraction of numerous plasmas over
      a broad range of soft x-ray wavelengths confirming recent observations. The
      understanding of index of refraction at short wavelengths will become even more
      essential during the next decade as x-ray free electron lasers will become
      available to probe a wider variety of plasmas at higher densities and shorter
      wavelengths.

PMID- 16907196
TI  - Absorption and penetration of left-hand polarized waves related to polarization
      reversal causing electron cyclotron resonance.
AB  - Propagation and absorption of electromagnetic waves with electron cyclotron
      resonance (ECR) frequency are investigated for the case of inhomogeneously
      magnetized plasmas, when the left-hand polarized wave (LHPW) is selectively
      launched. The LHPW with axisymmetric-azimuthal and second-order radial modes is
      absorbed near the ECR point at any radial position, which is caused by the
      polarization reversal to the right-hand polarized wave. On the other hand, it is
      clarified that the LHPW with fundamental radial mode penetrates the ECR point
      without polarization reversal. In addition, it is theoretically suggested that
      polarization reversal can partially occur in the plasma column for the case of
      nonaxisymmetric modes.

PMID- 16907197
TI  - Generation of Cherenkov superradiance pulses with a peak power exceeding the
      power of the driving short electron beam.
AB  - Theoretical investigation of a short electron beam (extended bunch) interaction
      with a backward wave propagating in a slow wave structure demonstrates the
      possibility of producing ultrashort superradiance pulses with a peak power which
      exceeds the power of the driving beam (conversion factor K>1). It is shown that a
      nonuniform slow wave structure with optimized profile is beneficial in order to
      increase the conversion factor. The results of theoretical analysis are confirmed
      by the experiments. At X band using the SINUS-150 accelerator (4 ns, 330 kV, 2.6
      kA) 0.6-0.8 ns superradiance pulses with a peak power of 1.2 GW and a conversion
      factor of 1.5 were obtained. Similar experiments at Ka-band based on the RADAN
      303 accelerator (1 ns, 290 kV, 2.5 kA) demonstrated production of the
      superradiance (SR) pulse with duration 200 ps and peak power about 1 GW
      (conversion factor of 1.4).

PMID- 16907198
TI  - Generation and control of optical vortices using left-handed materials.
AB  - Optical vortices are shown to be generated in the near-field through interference
      between a propagating wave and the amplified evanescent field in a slab of lossy
      left-handed material. While small loss adversely impacts the sub-wavelength
      performance in the lens application, the vortex character shown relies on some
      degree of imperfection. These vortices can be controlled by means of gain/loss
      and the incident field.

PMID- 16907199
TI  - Self-focusing arrest of femtosecond laser pulses in air at different pressures.
AB  - We study analytically and numerically the self-focusing arrest of femtosecond
      laser pulses in air at different pressures in the presence of an external focus
      lens. Analytical estimations as well as results of simulations show that the
      intensity at which the self-focusing arrest occurs is almost independent of the
      gas pressure. However, a dependence on the temperature is found. The Raman effect
      is taken into account, and an estimation of the intensity inside of filaments at
      high altitudes is given.

PMID- 16907200
TI  - Alfven soliton and emitted radiation in the presence of perturbations.
AB  - Soliton perturbation theory based on the inverse scattering transform method is
      applied to the derivative nonlinear Schrodinger equation, which describes
      nonlinear Alfven waves propagating quasiparallel to the external magnetic field.
      Radiative effects are considered. Spectral distributions of the emitted energy
      and magnetic helicity rates (in the wave number domain) are calculated
      analytically. Several forms of perturbations are considered, including the finite
      electric conductivity, the effect of resonant particles (nonlinear Landau
      damping), and the influence of the random inhomogeneity of the plasma density.
      The space structure of the radiative field is determined for a perturbation in
      the form of the finite electric conductivity.

PMID- 16907201
TI  - Finite-difference time-domain analysis of the tunneling and growing exponential
      in a pair of epsilon-negative and mu-negative slabs.
AB  - Pairing together planar material slabs with opposite signs for the real parts of
      their constitutive parameters has been shown to lead in the steady-state regime
      to interesting and unconventional properties that are not otherwise observable
      for single slabs, such as resonance, anomalous tunneling, transparency, and
      subwavelength imaging through the reconstruction of evanescent waves [A. Alu and
      N. Engheta, IEEE Trans. Antennas Prop. 51, 2558 (2003)]. The mechanics of the
      phenomenon, however, and in particular how the steady-state resonant response is
      reached, has not been explored. Here we analyze how a transient sinusoidal signal
      that starts at t=0 interacts with such a complementary pair of finite size using
      a finite-difference time-domain (FDTD) technique. Multiple reflections and
      transmissions at each interface are shown to build up to the eventual steady
      state response of the pair, and during this process one can observe how the
      "growing exponential" phenomenon may actually occur inside this bilayer. As with
      any resonant phenomena, the time response of this effect depends on the Q of the
      system, which is related to the geometrical and electrical parameters of the
      bilayer. Transparency to finite beams and reconstruction of the subwavelength
      details of an image are shown in the transient and steady-state response of the
      setup through one-dimensional and two-dimensional FDTD simulations.

PMID- 16907202
TI  - Subdiffractive light pulses in photonic crystals.
AB  - We investigate propagation of light pulses in photonic crystals in the vicinity
      of the zero diffraction point. We show that Gaussian pulses due to nonzero width
      of their temporal spectrum spread weakly in space and time during the
      propagation. We also find the family of nonspreading pulses, propagating
      invariantly in the vicinity of the zero diffraction point of photonic crystals.

PMID- 16907203
TI  - Relaxation of a one-dimensional gravitational system.
AB  - We study the relaxation towards thermodynamical equilibrium of a one-dimensional
      gravitational system. This model shows a series of critical energies E(cn) where
      different equilibria appear and we focus on the homogeneous (n=0), one-peak (n =
      +/-1), and two-peak (n=2) states. Using numerical simulations we investigate the
      relaxation to the stable equilibrium n = +/-1 of this N-body system starting from
      initial conditions defined by equilibria n=0 and n=2. We find that in a fashion
      similar to other long-range systems the relaxation involves a fast violent
      relaxation phase followed by a slow collisional phase as the system goes through
      a series of quasistationary states. Moreover, in cases where this slow second
      stage leads to a dynamically unstable configuration (two peaks with a high mass
      ratio) it is followed by a different sequence, "violent relaxation-slow
      collisional relaxation." We obtain an analytical estimate of the relaxation time
      t(2--> +/- 1)through the mean escape time of a particle from its potential well
      in a bistable system. We find that the diffusion and dissipation coefficients
      satisfy Einstein's relation and that the relaxation time scales as Ne(1/T) at low
      temperature, in agreement with numerical simulations.

PMID- 16907204
TI  - Discrete nonlinear Schrodinger equations with arbitrarily high-order
      nonlinearities.
AB  - A class of discrete nonlinear Schrodinger equations with arbitrarily high-order
      nonlinearities is introduced. These equations are derived from the same
      Hamiltonian using different Poisson brackets and include as particular cases the
      saturable discrete nonlinear Schrodinger equation and the Ablowitz-Ladik
      equation. As a common property, these equations possess three kinds of exact
      analytical stationary solutions for which the Peierls-Nabarro barrier is zero.
      Several properties of these solutions, including stability, discrete breathers,
      and moving solutions, are investigated.

PMID- 16907205
TI  - Two-dimensional Green's function theory for the electrodynamics of a rotating
      medium.
AB  - We derive an exact spectral representation for the Green's function of Maxwell
      equations in a two-dimensional homogeneous and rotating environment. The
      formulation is developed in the medium (noninertial) rest frame, and it
      represents the response to a point source, where both the source and observation
      points rotate together with the medium. The closed form expression for the
      Green's function is derived for (nonrelativistic) slowly rotating media at finite
      distances. An approximate expression for the efficient evaluation of the Green's
      function, that avoids laborious summation of rotating-medium spherical harmonics,
      is provided and tested against the exact expression. Furthermore, it is shown
      that our spectral theory can provide a broad view of the optical response of
      rotating systems, from which the classical Sagnac effect is obtained as a special
      case.

PMID- 16907206
TI  - Thermal emission and design in one-dimensional periodic metallic photonic crystal
      slabs.
AB  - We present a useful framework within which we can understand some of the physical
      phenomena that drive thermal emission in one-dimensional periodic metallic
      photonic crystals, emphasizing phenomenology and physical intuition. We perform
      detailed numerical calculations for these systems and find that polarization and
      periodicity play key roles in determining the types of physical phenomena that
      can arise. Two promising structures are identified as good candidates for thermal
      design. We conclude with a discussion of how the emissive properties of these
      systems can be tailored to our needs.

PMID- 16907207
TI  - Strong focusing properties and far-field focus in the two-dimensional photonic
      crystal-based concave lens.
AB  - We have demonstrated that the strong and far-field focusing of a point source and
      a plane wave in a two-dimensional photonic-crystal-based concave lens by the use
      of the standard finite-difference time-domain simulations. The effect of the
      distance between the point source and the lens on the focusing is discussed. The
      far-field focus of a plane wave is shown. In addition, a plane wave is formed
      with placing the source at the focus point. According to the calculation, the
      strong and good quality far-field focusing of the transmitted wave, explicitly
      following the well-known wave beam negative refraction law, can be realized.
      Moreover, the spatial frequencies information of the Bloch mode in multiple
      Brillouin zones is investigated in order to indicate the wave propagation in two
      different regions.

PMID- 16907208
TI  - Self-trapped spatiotemporal necklace-ring solitons in the Ginzburg-Landau
      equation.
AB  - We consider a class of self-trapped spatiotemporal solitons: spatiotemporal
      necklace-ring solitons, whose intensities are azimuthally periodically modulated.
      We reveal numerically that the spatiotemporal necklace-ring solitons carrying
      zero, integer, and even fractional angular momentum can be self-trapped over a
      huge propagation distance in the three-dimensional cubic-quintic complex Ginzburg
      Landau equation, even in the presence of random perturbations.

PMID- 16907209
TI  - Localized structures in a nonlinear wave equation stabilized by negative global
      feedback: one-dimensional and quasi-two-dimensional kinks.
AB  - We study the evolution of fronts in a nonlinear wave equation with global
      feedback. This equation generalizes the Klein-Gordon and sine-Gordon equations.
      Extending previous work, we describe the derivation of an equation governing the
      front motion, which is strongly nonlinear, and, for the two-dimensional case,
      generalizes the damped Born-Infeld equation. We study the motion of one- and two
      dimensional fronts, finding a much richer dynamics than for the classical case
      (with no global feedback), leading in most cases to a localized solution; i.e.,
      the stabilization of one phase inside the other. The nature of the localized
      solution depends on the strength of the global feedback as well as on other
      parameters of the model.

PMID- 16907210
TI  - Technique for backward particle tracking in a flow field.
AB  - A numerical method to determine the history of particle paths is presented and
      its application for mixing quantification is illustrated. When more than one
      source exists in a flow field, the current technique can reveal the particle's
      identity found in any time and place in the field, by backward tracking its
      origin. Since the particle position at a preceding time is not known, the
      velocity vector is implicit. To resolve this uncertainty, a three-stage iterative
      procedure is developed and implemented. The current particle velocity is
      multiplied by the time increment and the product is used to estimate the previous
      time increment particle position. Two velocity matrices are generated on a mesh
      around the estimated position. The first matrix is the Eulerian velocity field
      interpolated on the mesh. The second matrix contains velocity vectors that point
      to the current particle position. A correlation matrix is calculated from the two
      velocity matrices in order to resolve the actual particle position in the
      previous time increment. Determination of the time increments' size is performed
      by checking the maximum of the correlation matrix. The new algorithm was
      validated using a numerical solution of the confined twin-jet flow at low
      Reynolds number. This flow performs a Hopf bifurcation at a Reynolds number of
      about 30, therefore chaotic trajectories might exist in the flow. First, the
      convergence of the backward particle path to the streamlines in steady flow was
      demonstrated. Convergence of the particle paths for various time increments was
      achieved also at the unsteady two-dimensional confined twin-jet flow. When the
      flow has more than one source, the proposed tracking method can be applied to
      generate complete and ordered particle source images in any desired position and
      time in the flow field. Maps of particle sources are used to visualize the flow
      patterns and the stretched interface between the two fluid sources. Those maps
      are demonstrated as a powerful tool for mixing quantification and can be
      implemented also for pollution source detection and many other fluid dynamics
      applications.

PMID- 16907211
TI  - Equation-free dynamic renormalization in a glassy compaction model.
AB  - Combining dynamic renormalization with equation-free computational tools, we
      study the apparently asymptotically self-similar evolution of void distribution
      dynamics in the diffusion-deposition problem proposed by Stinchcombe and Depken
      [Phys. Rev. Lett. 88, 125701 (2002)]. We illustrate fixed point and dynamic
      approaches, forward as well as backward in time; these can be used to accelerate
      simulators of glassy dynamic phenomena.

PMID- 16907212
TI  - Damage-spreading simulations through exact relations for the two-dimensional
      Potts ferromagnet.
AB  - A powerful computational method for dealing with correlation functions in
      magnetic systems, based on damage-spreading simulations, is reviewed and tested,
      by investigating the q-state Potts ferromagnet, on a square lattice, at
      criticality. Exact relations involving special kinds of damage and the spin-spin
      correlation function, as well as the magnetization, are used. The efficiency of
      the method arises with a significant reduction of the finite-size effects, with
      respect to conventional Monte Carlo simulations. Correlation functions, which
      represent usually a hard task within this latter procedure, appear to be much
      more easily estimated through the present damage-spreading simulations. The
      effectiveness of the technique is illustrated by an accurate estimate of the
      exponent eta, of the spin-spin correlation function, for q=2, 3, and 4, with
      rather small lattice sizes. In the cases q > or = 5, an analysis of the
      magnetization is consistent with the well-known first-order phase transition.

PMID- 16907213
TI  - Kleinberg navigation in fractal small-world networks.
AB  - We study the Kleinberg problem of navigation in small-world networks when the
      underlying lattice is a fractal consisting of N>>1 nodes. Our extensive numerical
      simulations confirm the prediction that the most efficient navigation is attained
      when the length r of long-range links is taken from the distribution P(r)
      approximately r(-alpha), where alpha=d(f) is the fractal dimension of the
      underlying lattice. We find finite-size corrections to the exponent alpha,
      proportional to 1/(ln N)2.

PMID- 16907214
TI  - Periodic neural activity induced by network complexity.
AB  - We study a model for neural activity on the small-world topology of Watts and
      Strogatz and on the scale-free topology of Barabasi and Albert. We find that the
      topology of the network connections may spontaneously induce periodic neural
      activity, contrasting with nonperiodic neural activities exhibited by regular
      topologies. Periodic activity exists only for relatively small networks and
      occurs with higher probability when the rewiring probability is larger. The
      average length of the periods increases with the square root of the network size.

PMID- 16907215
TI  - Thouless-Anderson-Palmer equation and self-consistent signal-to-noise analysis
      for the Hopfield model with three-body interaction.
AB  - The self-consistent signal-to-noise analysis (SCSNA) is an alternative to the
      replica method for deriving the set of order parameter equations for associative
      memory neural network models and is closely related with the Thouless-Anderson
      Palmer equation (TAP) approach. In the recent paper by Shiino and Yamana the
      Onsager reaction term of the TAP equation has been found to be obtained from the
      SCSNA for Hopfield neural networks with two-body interaction. We study the TAP
      equation for an associative memory stochastic analog neural network with three
      body interaction to investigate the structure of the Onsager reaction term, in
      connection with the term proportional to the output characteristic to the SCSNA.
      We report on the SCSNA framework for analog networks with three-body interactions
      as well as provide a recipe based on the cavity concept that involves two
      cavities and the hybrid use of the SCSNA to obtain the TAP equation.

PMID- 16907216
TI  - Universal dynamics in the onset of a Hagen-Poiseuille flow.
AB  - The dynamics in the onset of a Hagen-Poiseuille flow of an incompressible liquid
      in a channel of circular cross section is well-studied theoretically. We use an
      eigenfunction expansion in a Hilbert space formalism to generalize the results to
      channels of an arbitrary cross section. We find that the steady state is reached
      after a characteristic time scale tau=(A/P)2(1/nu), where A and P are the cross
      sectional area and perimeter, respectively, and nu is the kinematic viscosity of
      the liquid. For the initial dynamics of the flow rate Q for t<<tau we find a
      universal linear dependence, Q(t)=Q(infinity) (alpha/C)(t/tau), where Q(infinity)
      is the asymptotic steady-state flow rate, alpha is the geometrical correction
      factor, and C=P2/A is the compactness parameter. For the long-time dynamics Q(t)
      approaches Q(infinity) exponentially on the time scale , but with a weakly
      geometry-dependent prefactor of order unity, determined by the lowest eigenvalue
      of the Helmholz equation.

PMID- 16907217
TI  - Shear viscosity of bulk suspensions at low Reynolds number with the three
      dimensional lattice Boltzmann method.
AB  - We report three-dimensional parallel Lagrangian particle simulations using the
      lattice Boltzmann method, conducted at a low Reynolds number. Using modified Lees
      Edwards boundary conditions and directly calculated viscous dissipation, we show
      that it is possible to recover excellent agreement with the Einstein viscosity
      formula in the low concentration limit and to predict viscosity corrections for
      larger concentrations.

PMID- 16907218
TI  - Comment on "Linking population-level models with growing networks: a class of
      epidemic models".
AB  - In this Comment, we show that the expression for as proposed by R. Breban, R.
      Vardavas, and S. Blower, Phys. Rev. E 72, 046110 (2005) is incorrect and we
      reveal the underlying conceptual mistake.

PMID- 16907220
TI  - Anomalous hydrodynamics and normal fluids in rapidly rotating Bose-Einstein
      condensates.
AB  - In rapidly rotating condensed Bose systems we show that there is a regime of
      anomalous hydrodynamics which coincides with the mean field quantum Hall regime.
      A consequence is the absence of a normal fluid in any conventional sense.
      However, even the superfluid hydrodynamics is not described by conventional
      Bernoulli and continuity equations. We show that there are constraints which
      connect spatial variations of density and phase and that the vortex positions are
      not the simplest description of the dynamics. We demonstrate, inter alia, a
      simple relation between vortices and surface waves. We show that the surface
      waves can emulate a "normal fluid," allowing dissipation by energy and angular
      momentum absorbtion from vortex motion in the trap. The time scale is sensitive
      to the initial configuration, which can lead to long-lived vortex patches-
      perhaps related to those observed at JILA.

PMID- 16907221
TI  - Structure of fermion nodes and nodal cells.
AB  - We study nodes of fermionic ground state wave functions. For two dimensions and
      higher we prove that spin-polarized, noninteracting fermions in a harmonic well
      have two nodal cells for arbitrary system size. The result extends to
      noninteracting or mean-field models in other geometries and to Hartree-Fock
      atomic states. Spin-unpolarized noninteracting states have multiple nodal cells;
      however, interactions and many-body correlations generally relax the multiple
      cells to the minimal number of two. With some conditions, this is proved for
      interacting two and higher dimensions harmonic fermion systems of arbitrary size
      using the Bardeen-Cooper-Schrieffer variational wave function.

PMID- 16907222
TI  - Proposal of an experimentally accessible measure of many-fermion entanglement.
AB  - We propose an experimentally accessible measure of entanglement in many-fermion
      systems that characterizes interaction-induced ground state correlations. It is
      formulated in terms of cross correlations of currents through resonant fermion
      levels weakly coupled to the probed system. The proposed entanglement measure
      vanishes in the absence of many-body interactions at zero temperature and it is
      related to measures of occupation number entanglement. We evaluate it for two
      examples of interacting electronic nanostructures.

PMID- 16907223
TI  - Hybrid quantum repeater using bright coherent light.
AB  - We describe a quantum repeater protocol for long-distance quantum communication.
      In this scheme, entanglement is created between qubits at intermediate stations
      of the channel by using a weak dispersive light-matter interaction and
      distributing the outgoing bright coherent-light pulses among the stations. Noisy
      entangled pairs of electronic spin are then prepared with high success
      probability via homodyne detection and postselection. The local gates for
      entanglement purification and swapping are deterministic and measurement-free,
      based upon the same coherent-light resources and weak interactions as for the
      initial entanglement distribution. Finally, the entanglement is stored in a
      nuclear-spin-based quantum memory. With our system, qubit-communication rates
      approaching 100 Hz over 1280 km with fidelities near 99% are possible for
      reasonable local gate errors.

PMID- 16907224
TI  - Experimental interference of independent photons.
AB  - Interference of photons emerging from independent sources is essential for modern
      quantum-information processing schemes, above all quantum repeaters and linear
      optics quantum computers. We report an observation of nonclassical interference
      of two single photons originating from two independent, separated sources, which
      were actively synchronized with a rms timing jitter of 260 fs. The resulting (two
      photon) interference visibility was (83+/-4)%.

PMID- 16907225
TI  - Time-symmetric fluctuations in nonequilibrium systems.
AB  - For nonequilibrium steady states, we identify observables whose fluctuations
      satisfy a general symmetry and for which a new reciprocity relation can be shown.
      Unlike the situation in recently discussed fluctuation theorems, these
      observables are time-reversal symmetric. That is essential for exploiting the
      fluctuation symmetry beyond linear response theory. In addition to time reversal,
      a crucial role is played by the reversal of the driving fields that further
      resolves the space-time action. In particular, the time-symmetric part in the
      space-time action determines the second order effects of the nonequilibrium
      driving.

PMID- 16907226
TI  - Hamiltonian dynamics reveals the existence of quasistationary states for long
      range systems in contact with a reservoir.
AB  - We introduce a Hamiltonian dynamics for the description of long-range interacting
      systems in contact with a thermal bath (i.e., in the canonical ensemble). The
      dynamics confirms statistical mechanics equilibrium predictions for the
      Hamiltonian mean field model and the equilibrium ensemble equivalence. We find
      that long-lasting quasistationary states persist in the presence of the
      interaction with the environment. Our results indicate that quasistationary
      states are indeed reproducible in real physical experiments.

PMID- 16907227
TI  - Self-avoiding random walk with multiple site weightings and restrictions.
AB  - We introduce a new class of models for polymer collapse, given by random walks on
      regular lattices which are weighted according to multiple site visits. A
      Boltzmann weight omegal is assigned to each (l+1)-fold visited lattice site, and
      self-avoidance is incorporated by restricting to a maximal number K of visits to
      any site via setting omegal=0 for l>or=K. In this Letter we study this model on
      the square and simple cubic lattices for the case K=3. Moreover, we consider a
      variant of this model, in which we forbid immediate self-reversal of the random
      walk. We perform simulations for random walks up to n=1024 steps using FlatPERM,
      a flat histogram stochastic growth algorithm. We find evidence that the existence
      of a collapse transition depends sensitively on the details of the model and has
      an unexpected dependence on dimension.

PMID- 16907228
TI  - Quasiperiodically driven ratchets for cold atoms.
AB  - We investigate experimentally the route to quasiperiodicity in a driven ratchet
      for cold atoms and examine the relationship between symmetries and transport
      while approaching the quasiperiodic limit. Depending on the specific form of
      driving, quasiperiodicity results in the complete suppression of transport, or in
      the restoration of the symmetries which hold for a periodic driving.

PMID- 16907229
TI  - Nuclear effects in neutrino induced coherent pion production at K2K and
      MiniBooNE.
AB  - The coherent pion production induced by neutrinos in nuclei is studied using a
      delta hole model in the local density approximation taking into account the
      renormalization of Delta properties in a nuclear medium. The pion absorption
      effects are included in an eikonal approximation. These effects give a large
      reduction in the total cross section. The numerical results for the total cross
      section are found to be consistent with recent experimental results from the K2K
      and MiniBooNE Collaborations and other older experiments in the intermediate
      energy region.

PMID- 16907231
TI  - Measurement of the asymmetry in the decay Omega+-->LamdaKappa+-->rhopi+Kappa+.
AB  - The asymmetry in the rho angular distribution in the sequential decay Omega+-
      >LamdaKappa+-->rhopi+Kappa+. has been measured to be
      alphaOmegaalphaLamda=[+1.16+/-0.18(stat)+/-0.17(syst)]x10(-2) using 1.89x10(6)
      unpolarized Omega+ decays recorded by the HyperCP (E871) experiment at Fermilab.
      Using the known value of alphaLamda, and assuming that alphaLamda=-alphaLamda,
      alphaOmega=[-1.81+/-0.28(stat)+/-0.26(syst)]x10(-2). A comparison between this
      measurement of alphaOmegaalphaLamda and recent measurements of
      alphaOmegaalphaLamda made by HyperCP shows no evidence of a violation of CP
      symmetry.

PMID- 16907233
TI  - Mechanism of angular momentum exchange between molecules and Laguerre-Gaussian
      beams.
AB  - We derive the interaction Hamiltonian between a diatomic molecule and a Laguerre
      Gaussian beam under the assumption of a small spread of the center of mass wave
      function of the molecule in comparison with the beam waist. Considering the
      dynamical variables of the center of mass, vibrational, rotational, and
      electronic motion, we show that, within the electronic dipole approximation, the
      orbital angular momentum of the field couples with the rotational and electronic
      motion. The changes in the transition probabilities and selection rules induced
      by the field orbital angular momentum and the applicability of the derived
      interaction mechanisms for polyatomic molecules are discussed.

PMID- 16907232
TI  - Near-threshold production of phi mesons in pp collisions.
AB  - The pp-->ppphi reaction has been studied at the Cooler Synchrotron COSY-Julich,
      using the internal beam and ANKE facility. Total cross sections have been
      determined at three excess energies epsilon near the production threshold. The
      differential cross section closest to threshold at epsilon=18.5 MeV exhibits a
      clear S wave dominance as well as a noticeable effect due to the proton-proton
      final-state interaction. Taken together with data for ppomega production, a
      significant enhancement of the phi/omega ratio of a factor 8 is found compared to
      predictions based on the Okubo-Zweig-Iizuka rule.

PMID- 16907234
TI  - Comparison study of atomic and molecular single ionization in the multiphoton
      ionization regime.
AB  - In this Letter, we report, for the first time in the multiphoton ionization
      regime, a comparison study of single-electron ionization of diatomic molecules
      versus rare gas atoms with virtually the same ionization potentials. In comparing
      N2+ to Ar+, a higher ion signal is seen in N2+ compared to Ar+ for linear
      polarization but the difference vanishes in circularly polarized light. In
      comparing O2+ to Xe+, we observe a suppression in O2+ compared to Xe+ for both
      linear and circular polarization but this suppression exhibits an intensity
      dependence; i.e., there is little suppression for O2+ at the lowest intensity
      range, but the suppression becomes increasingly stronger as the laser intensity
      increases. The multielectron screening model is used to discuss possible
      mechanisms of this intensity dependent suppression in O2+ in the multiphoton
      ionization regime.

PMID- 16907235
TI  - Analytical control of molecular excitations including strong field polarization
      effects.
AB  - An analytical scheme is presented for designing a laser pulse to excite H2 from
      one specified vibrational-rotational state to another. The scheme is based on an
      adiabatic two-state approximation in a Floquet picture. By continuously and
      smoothly changing the laser frequency, we explicitly harness the dynamic Stark
      shifts and maintain resonance between the dressed diabatic states during laser
      molecule interaction. The explicit time-dependent solution of the Schrodinger
      equation confirms the validity and efficacy of the analytically designed laser
      pulses. The scheme depends on the molecular polarizability to achieve its control
      objectives.

PMID- 16907236
TI  - Universal reduced potential function for diatomic systems.
AB  - The potential energy functions of 200 diatomic systems, with dissociation
      energies De ranging from few eV to hundreds of mueV, are well described by a new
      three-parameter potential energy function. Identification of the evaluated values
      of a dimensionless quantity, xin=L2/Ln [Ln=(n!De/fn)1/n, a scaled length
      parameter, and fn, the nth force constant evaluated at the equilibrium
      internuclear distance Re], is proposed as a reliable criterion to search for the
      universal scaling features of potentials and spectroscopic constants for bound
      diatomic systems. Our study suggests a useful approach to predicting future
      molecular spectroscopic constants.

PMID- 16907237
TI  - Three-dimensional images for electron-impact single ionization of He: complete
      and comprehensive (e, 2e) benchmark data.
AB  - Comprehensive fully differential cross sections for electron emission into all
      three spatial dimensions are presented for 1 keV and 102 eV electron-impact
      single ionization of helium using an advanced reaction microscope. Surprising out
      of-plane contributions, traced back to an interference term in a perturbation
      expansion by comparison with ion-impact data, severely challenge theoretical
      models that accurately predict coplanar emission. The data represent the ultimate
      benchmark for recently developed exact theoretical descriptions of the most
      fundamental three-body quantum problems.

PMID- 16907238
TI  - Reactive scattering damage to DNA components by hyperthermal secondary ions.
AB  - We have observed reactive scattering damage to fundamental DNA building blocks by
      the type of hyperthermal secondary ions that are produced along heavy ion tracks
      in biological media. Reactions include carbon abstraction by N+, and hydrogen
      abstraction by O- and N+, at collision energies down to 1 eV. Our results show
      that localized reactive scattering by hyperthermal secondary fragments can lead
      to important physicochemical damage to DNA in cells irradiated by heavy ions.
      This suggests a fundamentally different picture of nascent DNA damage induced by
      heavy ion tracks, compared to conventional (x or gamma) radiation tracks.

PMID- 16907239
TI  - Determination of the antiproton-to-electron mass ratio by precision laser
      spectroscopy of pHe+.
AB  - A femtosecond optical frequency comb and continuous-wave pulse-amplified laser
      were used to measure 12 transition frequencies of antiprotonic helium to
      fractional precisions of (9-16)x10(-9). One of these is between two states having
      microsecond-scale lifetimes hitherto unaccessible to our precision laser
      spectroscopy method. Comparisons with three-body QED calculations yielded an
      antiproton-to-electron mass ratio of Mp/me=1836.152674(5).

PMID- 16907240
TI  - Experimental evidence of interatomic coulombic decay from the auger final states
      in argon dimers.
AB  - Interatomic Coulombic decay (ICD) from an Auger-final dicationic state is
      observed in the Ar dimer. A 2p inner-shell vacancy created by photoionization is
      replaced with 3s and 3p vacancies via intra-atomic Auger decay. The Auger-final
      dicationic state is subject to ICD in which one of the 3p electrons in the same
      Ar atom fills the 3s vacancy while one of the 3p electrons from the neighboring
      Ar atom is emitted as an ICD electron. This ICD process is unambiguously
      identified by electron-ion-ion coincidence spectroscopy in which the kinetic
      energy of the ICD electron and the kinetic energy release between Ar+ and Ar2+
      are measured in coincidence.

PMID- 16907241
TI  - Observation of dynamic localization in periodically curved waveguide arrays.
AB  - We report on a direct experimental observation of dynamic localization (DL) of
      light in sinusoidally-curved lithium-niobate waveguide arrays which provides the
      optical analog of DL for electrons in periodic potentials subjected to ac
      electric fields as originally proposed by Dunlap and Kenkre [Phys. Rev. B 34,
      3625 (1986)10.1103/PhysRevB.34.3625]. The theoretical condition for DL in a
      sinusoidal field is experimentally demonstrated.

PMID- 16907242
TI  - Imaging single quantum dots in three-dimensional photonic crystals.
AB  - Performing fluorescence wide-field microscopy we have imaged single semiconductor
      quantum dots deep inside a 3-dimensional photonic crystal prepared from colloidal
      polymer beads. Exploring the emission diffraction patterns in defocused images of
      quantum dots we demonstrate that the direction-dependent photonic stop band
      imprints an anisotropy to the angular emission of a single quantum dot. Hence a
      single, quasi-point-like emitter is manipulated to radiate its photons only to
      certain well-defined directions by means of the anisotropic light propagation in
      photonic crystals. The experiments thus provide new routes to evaluate local,
      frequency selective optical properties in 3-dimensional photonic crystals
      employing single emitters.

PMID- 16907243
TI  - Correcting ray optics at curved dielectric microresonator interfaces: phase-space
      unification of Fresnel filtering and the Goos-Hanchen shift.
AB  - We develop an amended ray-optics description for reflection at the curved
      dielectric interfaces of optical microresonators which improves the agreement
      with wave optics by about one order of magnitude. The corrections are separated
      into two contributions of similar magnitude, corresponding to ray displacement in
      independent quantum-phase-space directions, which can be identified with Fresnel
      filtering and the Goos-Hanchen shift, respectively. Hence we unify two effects
      which only have been studied separately in the past.

PMID- 16907244
TI  - Resonance pacemakers in excitable media.
AB  - Chemical waves are initiated in an excitable medium by resonance with local
      periodic forcing of the excitability. Experiments are carried out with a
      photosensitive Belousov-Zhabotinsky medium, in which the excitability is varied
      according to the intensity of the imposed illumination. Complex resonance
      patterns are exhibited as a function of the amplitude and frequency of the
      forcing. Local resonance-induced wave initiation transforms the medium globally
      from a quiescent excitable steady state to a periodic state of successive
      traveling waves.

PMID- 16907245
TI  - Synchronization of chaotic systems with coexisting attractors.
AB  - Synchronization of coupled oscillators exhibiting the coexistence of chaotic
      attractors is investigated, both numerically and experimentally. The route from
      the asynchronous motion to a completely synchronized state is characterized by
      the sequence of type-I and on-off intermittencies, intermittent phase
      synchronization, anticipated synchronization, and period-doubling phase
      synchronization.

PMID- 16907246
TI  - Crossing bifurcations and unstable dimension variability.
AB  - A crisis is a global bifurcation in which a chaotic attractor has a discontinuous
      change in size or suddenly disappears as a scalar parameter of the system is
      varied. In this Letter, we describe a global bifurcation in three dimensions
      which can result in a crisis. This bifurcation does not involve a tangency and
      cannot occur in maps of dimension smaller than 3. We present evidence of unstable
      dimension variability as a result of the crisis. We then derive a new scaling law
      describing the density of the new portion of the attractor formed in the crisis.
      We illustrate this new type of bifurcation with a specific example of a three
      dimensional chaotic attractor undergoing a crisis.

PMID- 16907247
TI  - Noise-induced front motion: signature of a global bifurcation.
AB  - We show that front motion can be induced by noise in a spatially extended
      excitable system with a global constraint. Our model system is a semiconductor
      superlattice exhibiting complex dynamics of electron accumulation and depletion
      fronts. The presence of noise induces a global change in the dynamics of the
      system forcing stationary fronts to move through the entire device. We
      demonstrate the effect of coherence resonance in our model; i.e., there is an
      optimal level of noise at which the regularity of front motion is enhanced.
      Physical insight is provided by relating the space-time dynamics of the fronts
      with a phase-space analysis.

PMID- 16907248
TI  - Anomalous slow fidelity decay for symmetry-breaking perturbations.
AB  - Symmetries as well as other special conditions can cause anomalous slowing down
      of fidelity decay. These situations will be characterized, and a family of random
      matrix models to emulate them generically presented. An analytic solution based
      on exponentiated linear response will be given. For one representative case the
      exact solution is obtained from a supersymmetric calculation. The results agree
      well with dynamical calculations for a kicked top.

PMID- 16907249
TI  - Formation and dynamics of dark solitons and vortices in quantum electron plasmas.
AB  - We present simulation studies of the formation and dynamics of dark solitons and
      vortices in quantum electron plasmas. The electron dynamics in the latter is
      governed by a pair of equations comprising the nonlinear Schrodinger and Poisson
      system of equations, which conserves the number of electrons as well as their
      momentum and energy. The present governing equations in one spatial dimension
      admit stationary solutions in the form a dark envelope soliton. The dynamics of
      the latter reveals its robustness. Furthermore, we numerically demonstrate the
      existence of cylindrically symmetric two-dimensional quantum electron vortices,
      which survive during collisions. The nonlinear structures presented here may
      serve the purpose of transporting information at quantum scales in ultracold
      micromechanical systems and dense plasmas, such as those created during intense
      laser-matter interactions.

PMID- 16907250
TI  - Collimated multi-MeV ion beams from high-intensity laser interactions with
      underdense plasma.
AB  - A beam of multi-MeV helium ions has been observed from the interaction of a short
      pulse high-intensity laser pulse with underdense helium plasma. The ion beam was
      found to have a maximum energy for He2+ of (40(+3)(-8)) MeV and was directional
      along the laser propagation path, with the highest energy ions being collimated
      to a cone of less than 10 degrees. 2D particle-in-cell simulations show that the
      ions are accelerated by a sheath electric field that is produced at the back of
      the gas target. This electric field is generated by transfer of laser energy to a
      hot electron beam, which exits the target generating large space-charge fields
      normal to its boundary.

PMID- 16907251
TI  - Fracture patterns generated by diffusion controlled volume changing reactions.
AB  - A simple two-dimensional model was developed for the growth of fractures in a
      chemically decomposing solid. Simulations were carried out under rapid chemical
      decomposition conditions for which the kinetics of fracture growth is controlled
      by diffusion of the volatile reaction product or the kinetics of evaporation. The
      growth of the fracture pattern is self-sustaining due to the volume reduction
      associated with the decomposition process. Consistent with the theoretical
      analysis of Yakobson [Phys. Rev. Lett. 67, 1590
      (1991)10.1103/PhysRevLett.67.1590], the fracture front propagates with a constant
      velocity v approximately=k2/3(Dl0)1/3 under evaporation controlled conditions and
      v approximately=D/l0 under diffusion controlled conditions, where k is the
      evaporation rate constant, D is the diffusion constant for the volatile reaction
      product in the solid, and l0 is the critical stable crack length. Under diffusion
      controlled conditions, the front width w scales as w approximately=(kl0/)D.

PMID- 16907252
TI  - Extraordinary plasticity of ductile bulk metallic glasses.
AB  - Shear bands generally initiate strain softening and result in low ductility of
      metallic glasses. In this Letter, we report high-resolution electron microscope
      observations of shear bands in a ductile metallic glass. Strain softening caused
      by localized shearing was found to be effectively prevented by
      nanocrystallization that is in situ produced by plastic flow within the shear
      bands, leading to large plasticity and strain hardening. These atomic-scale
      observations not only well explain the extraordinary plasticity that was recently
      observed in some bulk metallic glasses, but also reveal a novel deformation
      mechanism that can effectively improve the ductility of monolithic metallic
      glasses.

PMID- 16907253
TI  - Phase separating bulk metallic glass: a hierarchical composite.
AB  - Phase separating systems present a unique opportunity for designing composites
      with hierarchical microstructure at different length scales. We report here our
      success in synthesizing phase separating metallic glasses exhibiting the entire
      spectrum of microstructural possibilities expected from a phase separating
      system. In particular, we report novel core shell and hierarchical structures of
      spherical glassy droplets, resulting from critical wetting behavior and limited
      diffusion. We also report synthesis of a bulk phase separating glass in a
      metallic glass system. The combination of unique core shell and hierarchical
      structures in metallic glass systems opens a new avenue for the microstructure
      design of metallic glasses.

PMID- 16907254
TI  - Quantitative parameter-free prediction of simulated crystal-nucleation times.
AB  - We present direct comparisons between simulated crystal-nucleation times and
      theoretical predictions using a model of aluminum, and demonstrate that a
      quantitative prediction can be made. All relevant thermodynamic properties of the
      system are known, making the agreement of our simulation data with nucleation
      theories free of any adjustable parameters. The role of transient nucleation is
      included in the classical nucleation theory approach, and shown to be necessary
      to understand the observed nucleation times. The calculations provide an
      explanation on why nucleation is difficult to observe in simulations at moderate
      undercoolings. Even when the simulations are significantly larger than the
      critical nucleus, and when simulation times are sufficiently long, at moderate
      undercoolings the small concentration of critical nuclei makes the probability of
      the nucleation low in molecular dynamics simulations.

PMID- 16907255
TI  - In situ surface x-ray diffraction studies of homoepitaxial electrochemical growth
      on Au(100).
AB  - Direct in situ x-ray surface scattering studies of growth at a solid-liquid
      interface are demonstrated using the homoepitaxial electrodeposition on Au(100)
      as an example. With decreasing potential transitions from step-flow to layer-by
      layer growth, manifested by layering oscillations in the x-ray intensity, then to
      multilayer growth, and finally back to layer-by-layer growth were observed. This
      complex growth behavior can be explained by the effect of anion coadsorbates and
      the potential-dependent Au surface reconstruction on the Au surface mobility.

PMID- 16907256
TI  - Decompositional incommensurate growth of ferrocene molecules on a Au(111)
      surface.
AB  - Deviating from the common growth mode of molecular films of organic molecules
      where the adsorbates remain intact, we observe an essentially different growth
      behavior for metallocenes with a low temperature scanning tunneling microscope.
      Ferrocene molecules adsorb dissociatively and form a two layer structure. The top
      layer unit cell is composed of two tilted cyclopentadienyl (cp) rings, while the
      first layer consists of ferrocene molecules and cp-Fe complexes. Surprisingly a
      fourfold symmetry is observed for the top layer while the first layer displays
      threefold symmetry elements. It is this symmetry mismatch which induces an
      incommensurability between these layers in all except one surface direction. The
      top layer is weakly bonded and has an antiferromagnetic ground state as
      calculated by local spin density functional approximation.

PMID- 16907257
TI  - Origins of nanoscale heterogeneity in ultrathin films.
AB  - A key challenge in thin-film growth is controlling structure and composition at
      the atomic scale. We have used spatially resolved electron scattering to measure
      how the three-dimensional composition profile of an alloy film evolves with time
      at the nanometer length scale. We show that heterogeneity during the growth of Pd
      on Cu(001) arises naturally from a generic step-overgrowth mechanism relevant in
      many growth systems.

PMID- 16907230
TI  - Search for the rare decay B0-->tau+tau- at BABAR.
AB  - We present the results of a search for the decay B0-->tau+tau- in a data sample
      of (232+/-3)x10(6) Upsilon(4S)-->BB decays using the BABAR detector. Certain
      extensions of the standard model predict measurable levels of this otherwise rare
      decay. We reconstruct fully one neutral B meson and seek evidence for the signal
      decay in the rest of the event. We find no evidence for signal events and obtain
      Beta(B0->tau+tau-)<4.1x10(-3) at the 90% confidence level.

PMID- 16907258
TI  - Dynamics of individual single-walled carbon nanotubes in water by real-time
      visualization.
AB  - Individual single-walled carbon nanotubes (SWNTs) in aqueous suspension are
      visualized directly by fluorescence video microscopy. The fluorescent tagging is
      simple, biocompatible, and does not modify the SWNTs. The dynamics of individual
      SWNTs in water are observed and quantified for the first time. We measure the
      confined rotational diffusion coefficient and find it in reasonable agreement
      with predictions based on confined diffusion of dilute Brownian rods. We
      determine the critical concentration at which SWNTs in suspensions start
      interacting. By analyzing the fluctuating shape of SWNTs in the 3 to 5 microm
      range, we determine that their persistence length ranges between 32 and 174
      microm, in agreement with theoretical estimates; thus, commonly available SWNTs
      in liquids can be considered as rigid Brownian rods in the absence of imposed
      external fields or self-attractive forces.

PMID- 16907259
TI  - Theory of defect levels and the "band gap problem" in silicon.
AB  - Quantitative predictions of defect properties in semiconductors using density
      functional theory have been crippled by two issues: the supercell approximation,
      which has incorrect boundary conditions for an isolated defect, and approximate
      functionals, that drastically underestimate the band gap. I describe
      modifications to the supercell method that incorporate boundary conditions
      appropriate to point defects, identify a common electron reservoir for net charge
      for all defects, deal with defect banding, and incorporate bulk polarization. The
      computed level spectrum for an extended set of silicon defects spans the
      experimental gap, i.e., exhibits no band gap problem, and agrees remarkably well
      with experiment.

PMID- 16907260
TI  - Fermi surface and quasiparticle excitations of Sr2RhO4.
AB  - The electronic structure of the layered 4d transition metal oxide Sr2RhO4 is
      investigated by angle resolved photoemission. We find well-defined quasiparticle
      excitations with a highly anisotropic dispersion, suggesting a quasi-two
      dimensional Fermi-liquid-like ground state. Markedly different from the
      isostructural Sr2RuO4, only two bands with dominant Rh 4dxz,zy character
      contribute to the Fermi surface. A quantitative analysis of the photoemission
      quasiparticle band structure is in excellent agreement with bulk data. In
      contrast, it is found that state-of-the-art density functional calculations in
      the local density approximation differ significantly from the experimental
      findings.

PMID- 16907261
TI  - Voltage-induced metal-insulator transition in polythiophene field-effect
      transistors.
AB  - We have extensively studied the carrier transport in regio-regular polythiophene
      field-effect transistors (FETs) from room temperature to 4.2 K. At low
      temperatures, Zabrodskii plots (dlnsigma/dlnT) demonstrate that the gate voltage
      and source-drain voltage combine to induce the insulator-to-metal transition at a
      carrier density of 5x10(12) cm-2. The carrier transport in the insulating regime
      is well described by phonon assisted hopping in a disordered Fermi glass with
      Coulomb interaction between the hopping charge carrier and the opposite charge
      left behind, as described by Efros and Shklovskii.

PMID- 16907262
TI  - Spin-singlet small bipolarons in Nb-doped BaTiO3.
AB  - The magnetic susceptibility and the electrical resistivity of n-type BaTi1-xNbxO3
      have been measured over a wide temperature range. It is found that, for 0<x<0.2,
      dopant electrons form immobile spin-singlet small bipolarons with binding energy
      around 110 meV. For x=0.2, a maximum in the electrical resistivity around 15 K
      indicates a crossover from band to hopping transport of the charge carriers, a
      phenomenon expected but rarely observed in real polaronic systems.

PMID- 16907263
TI  - Determination of the mechanism for resonant scattering in LaMnO3.
AB  - The resonant multiple Bragg x-ray diffraction is used to study the forbidden
      (104) reflection in LaMnO3. Using the interference between the three-beam
      scattering and resonant scattering we can determine the phase of the resonant
      scattering. This phase is shown to be consistent with a model in which the
      resonant scattering is caused by the influence of the Mn-O bond length distortion
      rather than directly by the orbital ordering on the Mn 4p band structure.

PMID- 16907264
TI  - Coherence control of Hall charge and spin currents.
AB  - Using two-color optical coherence control techniques in intrinsic GaAs at 80 K
      with orthogonally polarized 70 fs, 1430 and 715 nm pulses, we generate a pure
      spin source current that yields a transverse Hall pure charge current; or
      alternatively, with parallel polarized pulses, we generate a pure charge source
      current that yields a pure spin current. By varying the relative phase or
      polarization of the incident pulses, one can effectively tune the type, magnitude
      and direction of both the source and transverse currents without application of
      electric or magnetic fields.

PMID- 16907265
TI  - Deterministic teleportation of electrons in a quantum dot nanostructure.
AB  - We present a proposal for deterministic quantum teleportation of electrons in a
      semiconductor nanostructure consisting of a single and a double quantum dot. The
      central issue addressed in this Letter is how to design and implement the most
      efficient--in terms of the required number of single and two-qubit operations-
      deterministic teleportation protocol for this system. Using a group-theoretical
      analysis, we show that deterministic teleportation requires a minimum of three
      single-qubit rotations and two entangling (square root SWAP) operations. These
      can be implemented for spin qubits in quantum dots using electron-spin resonance
      (for single-spin rotations) and exchange interaction (for square root SWAP
      operations).

PMID- 16907266
TI  - Sub-Poissonian shot noise in graphene.
AB  - We calculate the mode-dependent transmission probability of massless Dirac
      fermions through an ideal strip of graphene (length L, width W, no impurities or
      defects) to obtain the conductance and shot noise as a function of Fermi energy.
      We find that the minimum conductivity of order e2/h at the Dirac point (when the
      electron and hole excitations are degenerate) is associated with a maximum of the
      Fano factor (the ratio of noise power and mean current). For short and wide
      graphene strips the Fano factor at the Dirac point equals 1/3, 3 times smaller
      than for a Poisson process. This is the same value as for a disordered metal,
      which is remarkable since the classical dynamics of the Dirac fermions is
      ballistic.

PMID- 16907267
TI  - Generation and control of Greenberger-Horne-Zeilinger entanglement in
      superconducting circuits.
AB  - Going beyond the entanglement of microscopic objects (such as photons, spins, and
      ions), here we propose an efficient approach to produce and control the quantum
      entanglement of three macroscopic coupled superconducting qubits. By
      conditionally rotating, one by one, selected Josephson-charge qubits, we show
      that their Greenberger-Horne-Zeilinger (GHZ) entangled states can be
      deterministically generated. The existence of GHZ correlations between these
      qubits could be experimentally demonstrated by effective single-qubit operations
      followed by high-fidelity single-shot readouts. The possibility of using the
      prepared GHZ correlations to test the macroscopic conflict between the
      noncommutativity of quantum mechanics and the commutativity of classical physics
      is also discussed.

PMID- 16907268
TI  - Enhanced shot noise in tunneling through a stack of coupled quantum dots.
AB  - We have investigated the noise properties of the tunneling current through
      vertically coupled self-assembled InAs quantum dots. We observe super-Poissonian
      shot noise at low temperatures. For increased temperature this effect is
      suppressed. The super-Poissonian noise is explained by capacitive coupling
      between different stacks of quantum dots.

PMID- 16907269
TI  - Understanding the 5/2 fractional quantum Hall effect without the Pfaffian wave
      function.
AB  - It is demonstrated that an understanding of the 5/2 fractional quantum Hall
      effect can be achieved within the composite fermion theory without appealing to
      the Pfaffian wave function. The residual interaction between composite fermions
      plays a crucial role in establishing incompressibility at this filling factor.
      This approach has the advantage of being amenable to systematic perturbative
      improvements, and produces ground as well as excited states. It, however, does
      not relate to non-Abelian statistics in any obvious manner.

PMID- 16907270
TI  - Broad peak in the dx2-y2 superconducting correlation length as a function of hole
      concentration in the two-dimensional t-J model.
AB  - We have calculated high temperature series to 12th order in inverse temperature
      for singlet superconducting correlation functions of the 2D t-J model with s, dx2
      y2, and dxy symmetry pairs. Our calculations differ from previous work by
      removing disconnected pieces from the original four-point correlator and by
      treating the resulting pairing correlator as a matrix. We find the correlation
      length for dx2-y2 pairing grows significantly with decreasing temperature and
      develops a broad peak as a function of doping around delta=0.25 for T/J=0.25 at
      J/t=0.4. The correlation lengths for s and dxy symmetry remain small and do not
      display peaks. Antiferromagnetic spin correlations at low doping act to suppress
      the dx2-y2 and dxy superconducting correlation lengths.

PMID- 16907271
TI  - Phenomenological model of protected behavior in the pseudogap state of underdoped
      cuprate superconductors.
AB  - By extending previous work on the scaling of low frequency magnetic properties of
      the 2-1-4 cuprates to the 1-2-3 materials, we arrive at a consistent
      phenomenological description of protected behavior in the pseudogap state of the
      magnetically underdoped cuprates. Between zero hole doping and a doping level of
      approximately 0.22, it reflects the presence of a mixture of an insulating spin
      liquid that produces the measured magnetic scaling behavior and a Fermi liquid
      that becomes superconducting for doping levels x>0.06. Our analysis suggests the
      existence of two quantum critical points, at doping levels x approximately 0.05
      and x approximately 0.22, and that d-wave superconductivity in the pseudogap
      region arises from quasiparticle-spin liquid interaction, i.e., magnetic
      interactions between quasiparticles in the Fermi liquid induced by their coupling
      to the spin liquid excitations.

PMID- 16907272
TI  - Local observation of reverse-domain superconductivity in a superconductor
      ferromagnet hybrid.
AB  - Nanoscale magnetic and superconducting properties of the superconductor
      ferromagnet Nb/PbFe12O19 hybrid were studied as a function of applied magnetic
      fields. Low-temperature scanning laser microscopy (LTSLM) together with transport
      measurements were carried out in order to reveal local variations of
      superconductivity induced by the magnetic field template produced by the
      ferromagnetic substrate. Room temperature magnetic force microscopy (MFM) was
      performed and magnetization curves were taken at room and low temperature to
      investigate the magnetic properties of the hybrid. Comparative analysis of the
      LTSLM and the MFM images has convincingly demonstrated the presence of the
      reverse-domain superconductivity.

PMID- 16907273
TI  - Thermal conductivity of the pyrochlore superconductor KOs2O6: strong electron
      correlations and fully gapped superconductivity.
AB  - To elucidate the nature of the superconducting ground state of the geometrically
      frustrated pyrochlore KOs2O6 (Tc=9.6 K), the thermal conductivity was measured
      down to low temperatures (approximately Tc/100). We found that the quasiparticle
      mean free path is strikingly enhanced below a transition at Tp=7.8 K, indicating
      enormous electron inelastic scattering in the normal state. In magnetic fields,
      the conduction at T-->0 K is nearly constant up to approximately 0.4Hc2, in
      contrast with the rapid growth expected for superconductors with an anisotropic
      gap. This unambiguously indicates a fully gapped superconductivity, in contrast
      with previous studies. These results highlight that KOs2O6 is unique among
      superconductors with strong electron correlations.

PMID- 16907274
TI  - Spin waves in the frustrated kagome lattice antiferromagnet KFe3(OH)6(SO4)2.
AB  - The spin wave excitations of the S=5/2 kagome lattice antiferromagnet
      KFe3(OH)6(SO4)2 have been measured using high-resolution inelastic neutron
      scattering. We directly observe a flat mode which corresponds to a lifted "zero
      energy mode," verifying a fundamental prediction for the kagome lattice. A simple
      Heisenberg spin Hamiltonian provides an excellent fit to our spin wave data. The
      antisymmetric Dzyaloshinskii-Moriya interaction is the primary source of
      anisotropy and explains the low-temperature magnetization and spin structure.

PMID- 16907275
TI  - Unusual evolution of the magnetic interactions versus structural distortions in
      RMnO3 perovskites.
AB  - We report the refinement of x-ray powder diffraction together with magnetic and
      thermal conductivity measurements made on the entire family of RMnO3 perovskites
      prepared by melt growth or under high pressure. Analysis of the data has
      identified the origin of the transition from type-A to type-E magnetic order as a
      competition between t-orbital and e-orbital spin-spin interactions within each Mn
      O-Mn bond in the (001) planes, the e-orbital interactions decreasing with
      decreasing R3+-ion size.

PMID- 16907276
TI  - Low-temperature spin diffusion in a highly ideal S=1/2 Heisenberg
      antiferromagnetic chain studied by muon spin relaxation.
AB  - The organic radical-ion salt DEOCC-TCNQF4 contains linear chains of stacked
      molecules with significant Heisenberg antiferromagnet interactions along the
      chain and extremely weak interactions between the chains. Zero-field muSR has
      confirmed the absence of long-range magnetic order down to 20 mK and field
      dependent muSR is found to be consistent with diffusive motion of the spin
      excitations. The anisotropic spin dynamics and the upper boundary for magnetic
      ordering temperature both indicate interchain magnetic coupling /J'/<7 mK. As the
      intrachain coupling J is 110 K, /J'/J/ is significantly less than 10(-4). This
      system therefore provides one of the most ideal examples of the one-dimensional
      S=1/2 Heisenberg antiferromagnet yet discovered.

PMID- 16907277
TI  - Time-resolved spin-torque switching and enhanced damping in
      permalloy/Cu/permalloy spin-valve nanopillars.
AB  - We report time-resolved measurements of current-induced reversal of a free
      magnetic layer in Permalloy/Cu/Permalloy elliptical nanopillars at temperatures
      T=4.2 K to 160 K. Comparison of the data to Landau-Lifshitz-Gilbert macrospin
      simulations of the free layer switching yields numerical values for the spin
      torque and the Gilbert damping parameters as functions of T. The damping is
      strongly T dependent, which we attribute to the presence of an antiferromagnetic
      oxide layer around the perimeter of the Permalloy free layer. This adventitious
      antiferromagnetic oxide can have a major impact on spin-torque phenomena.

PMID- 16907278
TI  - Effect of orbital rotation and mixing on the optical properties of orthorhombic
      RMnO3 (R=La, Pr, Nd, Gd, and Tb).
AB  - We investigated the ab-plane absorption spectra of RMnO3 (R=La, Pr, Nd, Gd, and
      Tb) thin films. As the ionic radius of the R ion decreases, we observed a drastic
      suppression of the 2 eV peak, i.e., the intersite optical transition between spin
      and orbital-aligned states across the Mott gap. We found that, in addition to
      orbital rotation, orbital mixing in the orbital-ordered state should play an
      important role in the suppression of 2 eV peak. We also found that the spectral
      weight of 2 eV peak is proportional to the A-type antiferromagnetic ordering
      temperature, which suggests that the magnetic interaction should be sensitively
      coupled to the orbital degree of freedom.

PMID- 16907279
TI  - Long-distance entanglement in spin systems.
AB  - Most quantum system with short-ranged interactions show a fast decay of
      entanglement with the distance. In this Letter, we focus on the peculiarity of
      some systems to distribute entanglement between distant parties. Even in
      realistic models, like the spin-1 Heisenberg chain, sizable entanglement is
      present between arbitrarily distant particles. We show that long-distance
      entanglement appears for values of the microscopic parameters which do not
      coincide with known quantum critical points, hence signaling a transition
      detected only by genuine quantum correlations.

PMID- 16907280
TI  - Counterion-mediated attraction and kinks on loops of semiflexible polyelectrolyte
      bundles.
AB  - The formation of kinks in a loop of bundled polyelectrolyte filaments is analyzed
      in terms of the thermal fluctuations of charge density due to polyvalent
      counterions adsorbed on the polyelectrolyte filaments. It is found that the
      counterion-mediated attraction energy of filaments depends on their bending. By
      consideration of curvature elasticity energy and counterion-mediated attraction
      between polyelectrolyte filaments, the characteristic width of the kink and the
      number of kinks per loop is found to be in reasonable agreement with existing
      experimental data for rings of bundled actin filaments.

PMID- 16907281
TI  - Relaxation processes in supercooled confined water and implications for protein
      dynamics.
AB  - We show that the viscosity-related main (alpha) relaxation of confined water
      vanishes at a temperature where the volume required for the cooperative alpha
      relaxation becomes larger than the size of the geometrically confined water
      cluster. This occurs typically around 200 K, implying that above this temperature
      we observe a merged alpha-beta relaxation, whereas below it only a local (beta)
      relaxation remains. This also means that such confined supercooled water does not
      exhibit any true glass transition, in contrast to other liquids in similar
      confinements. Furthermore, it implies that deeply supercooled water in biological
      systems, such as membranes and proteins, generally shows only a local beta
      relaxation, a finding of importance for low temperature properties of biological
      materials.

PMID- 16907282
TI  - Probing the mechanical unzipping of DNA.
AB  - A study of the micromechanical unzipping of DNA in the framework of the Peyrard
      Bishop-Dauxois model is presented. We introduce a Monte Carlo technique that
      allows accurate determination of the dependence of the unzipping forces on
      unzipping speed and temperature. Our findings agree quantitatively with
      experimental results for homogeneous DNA, and for lamda-phage DNA we reproduce
      the recently obtained experimental force-temperature phase diagram. Finally, we
      argue that there may be fundamental differences between in vivo and in vitro DNA
      unzipping.

PMID- 16907283
TI  - Cytoskeleton influence on normal and tangent fluctuation modes in the red blood
      cells.
AB  - We argue that the paradoxal softness of the red blood cells (RBC) in fluctuation
      experiments is apparent. We show that the effective surface shear modulus mus of
      the RBC obtained from fluctuation data and that measured in static deformation
      experiments have the same order of magnitude. In the RBC model developed for this
      purpose the spectrin network cytoskeleton with the bulk shear modulus estimated
      as mu approximately 105-165 Pa contributes to both normal and tangent
      fluctuations of the system and confines the membrane fluctuations. The calculated
      ratio of the mean-square amplitudes <X2n>/<X2t> is 2-3 orders of magnitude
      smaller than it is in the free membrane with the same bending and shear moduli.

PMID- 16907284
TI  - Soft nanopolyhedra as a route to multivalent nanoparticles.
AB  - Computer simulations show that end-grafted immiscible homopolymers can confer
      multivalence to nanoparticles, resulting in soft nanopolyhedra with structures
      identical to those found in small clusters of colloidal microspheres.
      Unprecedented structure tunability is demonstrated by several structure
      transition sequences, including a reentrant transition, induced by varying
      composition, polymer lengths, or grafting patterns. These results suggest a new
      method for fabricating nanoparticles with precisely controlled numbers and
      locations of functional sites (i.e., multivalent nanoparticles).

PMID- 16907285
TI  - Comment on "measurements of energetic proton transport through magnetized plasma
      from intense laser interactions with solids".

PMID- 16907287
TI  - Comment on "sodium pyroxene NaTiSi2O6: possible haldane spin-1 chain system".

PMID- 16907289
TI  - Limit on nonlocality in any world in which communication complexity is not
      trivial.
AB  - Bell proved that quantum entanglement enables two spacelike separated parties to
      exhibit classically impossible correlations. Even though these correlations are
      stronger than anything classically achievable, they cannot be harnessed to make
      instantaneous (faster than light) communication possible. Yet, Popescu and
      Rohrlich have shown that even stronger correlations can be defined, under which
      instantaneous communication remains impossible. This raises the question: Why are
      the correlations achievable by quantum mechanics not maximal among those that
      preserve causality? We give a partial answer to this question by showing that
      slightly stronger correlations would result in a world in which communication
      complexity becomes trivial.

PMID- 16907290
TI  - d-Wave resonating valence bond states of fermionic atoms in optical lattices.
AB  - We study controlled generation and measurement of superfluid d-wave resonating
      valence bond (RVB) states of fermionic atoms in 2D optical lattices. Starting
      from loading spatial and spin patterns of atoms in optical superlattices as pure
      quantum states from a Fermi gas, we adiabatically transform this state to an RVB
      state by a change of the lattice parameters. Results of exact time-dependent
      numerical studies for ladders systems are presented, suggesting generation of RVB
      states on a time scale smaller than typical experimental decoherence times.

PMID- 16907291
TI  - Quantum manipulation of trapped ions in two dimensional coulomb crystals.
AB  - We show that a large number of ions forming a 2D Coulomb crystal provides an
      almost ideal system for scalable quantum computation and quantum simulation. In
      particular, the coupling of the internal states to the motion of the ions
      transverse to the crystal plane allows one to implement two-qubit quantum gates.
      We analyze in detail the decoherence induced by anharmonic couplings, and show
      that very high gate fidelities can be achieved with current experimental setups.

PMID- 16907292
TI  - Hybrid particle-field simulations of polymer nanocomposites.
AB  - We present a theoretical framework and computer simulation methodology for
      investigating the equilibrium structure and properties of mesostructured
      polymeric fluids with embedded colloids or nanoparticles. The method is based on
      a field-theoretic description of the fluid in which particle coordinates and
      chemical potential field variables are simultaneously updated. The fluid model
      can contain polymers of arbitrary chemical and architectural complexity, along
      with particles of all shapes, sizes, and surface treatments. Simulation results
      are compared with experiments conducted on polystyrene (PS)-functionalized Au
      nanoparticles in a PS-P2VP diblock copolymer melt.

PMID- 16907293
TI  - Regular phantom black holes.
AB  - We study self-gravitating, static, spherically symmetric phantom scalar fields
      with arbitrary potentials (favored by cosmological observations) and single out
      16 classes of possible regular configurations with flat, de Sitter, and anti-de
      Sitter asymptotics. Among them are traversable wormholes, bouncing Kantowski
      Sachs (KS) cosmologies, and asymptotically flat black holes (BHs). A regular BH
      has a Schwarzschild-like causal structure, but the singularity is replaced by a
      de Sitter infinity, giving a hypothetic BH explorer a chance to survive. It also
      looks possible that our Universe has originated in a phantom-dominated collapse
      in another universe, with KS expansion and isotropization after crossing the
      horizon. Explicit examples of regular solutions are built and discussed. Possible
      generalizations include k-essence type scalar fields (with a potential) and
      scalar-tensor gravity.

PMID- 16907294
TI  - Measurement of forward-backward asymmetry and Wilson coefficients in B --> K*l+l
      .
AB  - We report the first measurement of the forward-backward asymmetry and the ratios
      of Wilson coefficients and in A9/A7 and A10/A7 in B --> K*l+l-, where l
      represents an electron or a muon. We find evidence for the forward-backward
      asymmetry with a significance of 3.4sigma. The results are obtained from a data
      sample containing 386 x 10(6) BB pairs that were collected on the Y(4S) resonance
      with the Belle detector at the KEKB asymmetric-energy e+e- collider.

PMID- 16907297
TI  - Anomalous viscosity of an expanding quark-gluon plasma.
AB  - We argue that an expanding quark-gluon plasma has an anomalous viscosity, which
      arises from interactions with dynamically generated color fields. We derive an
      expression for the anomalous viscosity in the turbulent plasma domain and apply
      it to the hydrodynamic expansion phase, when the quark-gluon plasma is near
      equilibrium. The anomalous viscosity dominates over the collisional viscosity for
      weak coupling and not too late times. This effect may provide an explanation for
      the apparent "nearly perfect" liquidity of the matter produced in nuclear
      collisions at the Relativistic Heavy Ion Collider without the assumption that it
      is a strongly coupled state.

PMID- 16907298
TI  - Measurement of the Ec.m. = 184 keV resonance strength in the 26gAl (p, gamma)27
      Si reaction.
AB  - The strength of the Ec.m. = 184 keV resonance in the 26gAl(p, gamma)27 reaction
      has been measured in inverse kinematics using the DRAGON recoil separator at
      TRIUMF's ISAC facility. We measure a value of omega gamma = 35 +/- 7 microeV and
      a resonance energy of Ec.m. = 184 +/- 1 keV, consistent with p-wave proton
      capture into the 7652(3) keV state in 27Si, and discuss the implications of these
      values for 26GAl nucleosynthesis in typical oxygen-neon white-dwarf novae.

PMID- 16907299
TI  - Observation of strong low-lying E1 strength in the two-neutron halo nucleus 11Li.
AB  - An exclusive measurement has been made of the Coulomb dissociation of the two
      neutron halo nucleus 11Li at 70 MeV/nucleon at RIKEN. Strong low-energy (soft) E1
      excitation is observed, peaked at about Ex = 0.6 MeV with B(E1) = 1.42(18) e2fm2
      for Erel < or = 3 MeV, which was largely missed in previous measurements. This
      excitation represents the strongest E1 transition ever observed at such low
      excitation energies. The spectrum is reproduced well by a three-body model with a
      strong two-neutron correlation, which is further supported by the E1 non-energy
      weighted cluster sum rule.

PMID- 16907300
TI  - Large velocity capture range and low temperatures with cavities.
AB  - There are interesting modifications to the Doppler force when atoms strongly
      couple to an optical cavity. In particular, there is the possibility to increase
      the velocity capture range while maintaining a final temperature close to the
      Doppler limit. The mechanism is based on the multiple absorption emissions of
      each cavity photon. A previously reported counterintuitive Doppler effect is
      clarified.

PMID- 16907301
TI  - g-Factor of heavy ions: a new access to the fine structure constant.
AB  - A possibility for a determination of the fine structure constant in experiments
      on the bound-electron g-factor is examined. It is found that studying a specific
      difference of the g-factors of B- and H-like ions of the same spinless isotope in
      the Pb region to the currently accessible experimental accuracy of 7 x 10(-10)
      would lead to a determination of the fine structure constant to an accuracy which
      is better than that of the currently accepted value. Further improvements of the
      experimental and theoretical accuracy could provide a value of the fine structure
      constant which is several times more precise than the currently accepted one.

PMID- 16907296
TI  - Evidence for large direct CP violation in B+/- --> rho(770)0K+/- from analysis of
      three-body charmless B+/- --> K+/-pi+/-pi+/- decays.
AB  - We report results on a Dalitz analysis of three-body charmless B+/- --> K+/-pi+/
      pi+/- decay including searches for direct CP violation. We report the first
      observation of the decay B+/- --> f2(1270)K+/- with a statistical significance
      above 6sigma. We also observe first evidence for large direct CP violation in the
      B+/- --> rho(770)0K+/- channel. The results are obtained with a data sample that
      contains 386 10(6) BB pairs collected at the Y(4s) resonance with the Belle
      detector at the KEKB asymmetric-energy e+e- collider.

PMID- 16907302
TI  - Microfabricated surface-electrode ion trap for scalable quantum information
      processing.
AB  - Individual laser-cooled 24Mg+ ions are confined in a linear Paul trap with a
      novel geometry where gold electrodes are located in a single plane and the ions
      are trapped 40 microm above this plane. The relatively simple trap design and
      fabrication procedure are important for large-scale quantum information
      processing (QIP) using ions. Measured ion motional frequencies are compared to
      simulations. Measurements of ion recooling after cooling is temporarily suspended
      yield a heating rate of approximately 5 motional quanta per millisecond for a
      trap frequency of 2.83 MHz, sufficiently low to be useful for QIP.

PMID- 16907303
TI  - Energy-dependent excitation cross section measurements of the diagnostic lines of
      Fe XVII.
AB  - By implementing a large-area, gain-stabilized microcalorimeter array on an
      electron beam ion trap, the electron-impact excitation cross sections for the
      dominant x-ray lines in the Fe XVII spectrum have been measured as a function of
      electron energy establishing a benchmark for atomic calculations. The results
      show that the calculations consistently predict the cross section of the
      resonance line to be significantly larger than measured. The lower cross section
      accounts for several problems found when modeling solar and astrophysical Fe XVII
      spectra.

PMID- 16907304
TI  - Distillation of squeezing from non-Gaussian quantum states.
AB  - We show that single copy distillation of squeezing from continuous variable non
      Gaussian states is possible using linear optics and conditional homodyne
      detection. A specific non-Gaussian noise source, corresponding to a random linear
      displacement, is investigated experimentally. Conditioning the signal on a tap
      measurement, we observe probabilistic recovery of squeezing.

PMID- 16907305
TI  - Strength distributions and symmetry breaking in coupled microwave billiards.
AB  - Flat microwave cavities can be used to experimentally simulate quantum mechanical
      systems. By coupling two such cavities, we study the equivalent to symmetry
      breaking in quantum mechanics. As the coupling is tunable, we can measure
      resonance strength distributions as a function of the symmetry breaking. We
      analyze the data by employing a qualitative model based on random matrix theory
      and show that the results derived from the strength distribution are consistent
      with those previously obtained from spectral statistics.

PMID- 16907306
TI  - Estimating the Shannon entropy: recurrence plots versus symbolic dynamics.
AB  - Recurrence plots were first introduced to quantify the recurrence properties of
      chaotic dynamics. A few years later, the recurrence quantification analysis was
      introduced to transform graphical representations into statistical analysis.
      Among the different measures introduced, a Shannon entropy was found to be
      correlated with the inverse of the largest Lyapunov exponent. The discrepancy
      between this and the usual interpretation of a Shannon entropy is solved here by
      using a new definition--still based on the recurrence plots--and it is verified
      that this new definition is correlated with the largest Lyapunov exponent, as
      expected from the Pesin conjecture. A comparison with a Shannon entropy computed
      from symbolic dynamics is also provided.

PMID- 16907307
TI  - Emergence of coherence in complex networks of heterogeneous dynamical systems.
AB  - We present a general theory for the onset of coherence in collections of
      heterogeneous maps interacting via a complex connection network. Our method
      allows the dynamics of the individual uncoupled systems to be either chaotic or
      periodic, and applies generally to networks for which the number of connections
      per node is large. We find that the critical coupling strength at which a
      transition to synchrony takes place depends separately on the dynamics of the
      individual uncoupled systems and on the largest eigenvalue of the adjacency
      matrix of the coupling network. Our theory directly generalizes the Kuramoto
      model of equal strength all-to-all coupled phase oscillators to the case of
      oscillators with more realistic dynamics coupled via a large heterogeneous
      network.

PMID- 16907308
TI  - Dynamics of precipitation pattern formation at geothermal hot springs.
AB  - We formulate and model the dynamics of spatial patterns arising during the
      precipitation of calcium carbonate from a supersaturated shallow water flow. The
      model describes the formation of travertine deposits at geothermal hot springs
      and rimstone dams of calcite in caves. We find explicit solutions for travertine
      domes at low flow rates, identify the linear instabilities which generate dam and
      pond formation on sloped substrates, and present simulations of statistical
      landscape evolution.

PMID- 16907309
TI  - Polyhedra formation and transient cone ejection of a resonant microdrop forced by
      an ac electric field.
AB  - New deformation or fission phenomena are reported for microdrops driven by an ac
      electric field at their resonant frequencies. The Maxwell forces that pull out
      the vertices from a drop can be enhanced when the ac frequency is comparable to
      both the drop resonant frequency and the inverse charge relaxation time of the
      diffuse layer. The selected polyhedra possess symmetries that ensure a global
      force balance of the Maxwell forces and a linear dimension consistent with a
      sphere whose nth harmonic (n is up to six in the observation) coincides with the
      applied ac frequency. At high voltages, the resonant focusing of charges by the
      vibration modes produces evenly distributed and transient Taylor cones that can
      eject charged nanodrops.

PMID- 16907310
TI  - Meandering rivulets on a plane: a simple balance between inertia and capillarity.
AB  - Experiments on streams of water flowing down a rigid substrate have been
      performed for various plate inclinations and flow rates, and we focused on the
      regime of stationary meanders. The outcome is that (i) the flow is highly
      hysteretic--the shape of the meanders varies with flow rate only for increasing
      flow rates, and the straight rivulet regime does not appear for decreasing flow
      rate, and (ii) a simple force balance, including inertia, capillary forces, and
      also hysteresis of wetting, accounts well for the experimental instability
      threshold flow rate and for the final radius of curvature of the meanders.

PMID- 16907311
TI  - Measurement and 3D simulation of self-organized filaments in a barrier discharge.
AB  - We report on pattern formation phenomena in the filamentary dielectric barrier
      discharge between plane glass electrodes. It is for the first time that a three
      dimensional (3D) self-organized glow pattern was both observed in an actual
      experiment and directly calculated in a full 3D discharge simulation in a
      quantitative manner. Specifically, we investigate the genesis of periodic
      patterns during the first breakdowns. Despite our simple drift-diffusion
      discharge model, the correspondence of experimental and numerical findings is
      surprisingly good.

PMID- 16907312
TI  - Torus instability.
AB  - The expansion instability of a toroidal current ring in low-beta magnetized
      plasma is investigated. Qualitative agreement is obtained with experiments on
      spheromak expansion and with essential properties of solar coronal mass
      ejections, unifying the two apparently disparate classes of fast and slow coronal
      mass ejections.

PMID- 16907313
TI  - Broadband dielectric function of nonequilibrium warm dense gold.
AB  - We report on the first single-state measurement of the broadband (450-800 nm)
      dielectric function of gold isochorically heated by a femtosecond laser pulse to
      energy densities of 10(6) - 10(7) J/kg. A Drude and an interband component are
      clearly seen in the imaginary part of the dielectric function. The Drude
      component increases with energy density while the interband component shows both
      enhancement and redshift. This is in strong disagreement with predictions of a
      recent calculation of dielectric function based on limited Brillouin zone
      sampling.

PMID- 16907295
TI  - Search for T, CP, and CPT violation in B0-B0 mixing with inclusive dilepton
      events.
AB  - We report the results of a search for T, CP, CPT, and violation in B0-B0 mixing
      using an inclusive dilepton sample collected by the BABAR experiment at the PEP
      II factory. Using a sample of 232 x 10(6) BB pairs, we measure the T and CP
      violation parameter |q/p| - 1 = (-0.8 +/- 2.7(stat) +/- 1.9(syst) x 10(-3), and
      the CPT and CP parameters Imz = (13.9 +/- 7.3(stat) +/- 3.2(syst)) x 10(-3) and
      Delta Gamma x Rez = (7.1 +/- 3.9(stat) +/- 2.0(stat)) x 10(-3) ps(-1). The
      statistical correlation between the measurements of Imz and Delta Gamma x Rez is
      76%.

PMID- 16907314
TI  - Toroidal symmetry of the geodesic acoustic mode zonal flow in a tokamak plasma.
AB  - The toroidal symmetry of the geodesic acoustic mode (GAM) zonal flows is
      identified with toroidally distributed three step Langmuir probes at the edge of
      the HuanLiuqi-2A (commonly referred to as HL-2A) tokamak plasmas for the first
      time. High coherence of both the GAM and the ambient turbulence for the
      toroidally displaced measurements along a magnetic field line is observed, in
      contrast with the high coherence of the GAM but low coherence of the ambient
      turbulence when the toroidally displaced measurements are not along the same
      field line. The radial and poloidal features of the flows are also simultaneously
      determined. The nonlinear three wave coupling between the high frequency
      turbulent fluctuations and the flows is demonstrated to be a plausible formation
      mechanism of the flows.

PMID- 16907315
TI  - Energy loss of a charged particle moving over a 2D strongly coupled dusty plasma.
AB  - We use molecular dynamics (MD) simulation to evaluate the energy loss of a
      charged projectile moving parallel to a two-dimensional strongly coupled dusty
      plasma and compare the results with those obtained from the quasilocalized charge
      approximation (QLCA) and the Vlasov-random phase approximation. Good agreement is
      found between the QLCA and MD results when the projectile-dust coupling is weak.
      In the opposite regime, nonlinear effects in the dust-layer response render the
      QLCA model increasingly inadequate for calculating the energy losses at low
      projectile speeds.

PMID- 16907316
TI  - Optimum hot electron production with low-density foams for laser fusion by fast
      ignition.
AB  - We propose a foam cone-in-shell target design aiming at optimum hot electron
      production for the fast ignition. A thin low-density foam is proposed to cover
      the inner tip of a gold cone inserted in a fuel shell. An intense laser is then
      focused on the foam to generate hot electrons for the fast ignition. Element
      experiments demonstrate increased laser energy coupling efficiency into hot
      electrons without increasing the electron temperature and beam divergence with
      foam coated targets in comparison with solid targets. This may enhance the laser
      energy deposition in the compressed fuel plasma.

PMID- 16907317
TI  - Application of bond constraint theory to the switchable optical memory material
      Ge2Sb2Te5.
AB  - A new extended x-ray-absorption fine structure spectroscopy study of local
      bonding identifies for the first time significant concentrations of Ge-Ge bonds
      in amorphous Ge2Sb2Te5. The study provides a new understanding of the local
      molecular structure of this phase-change material. Application of bond constraint
      theory indicates that the amorphous phase is an ideal network structure in which
      the average number of constraints per atom equals the network dimensionality.
      Analysis within this framework imparts new and significant insights concerning
      the nature of the reversible optically driven amorphous-crystalline phase
      transition of Ge2Sb2Te5.

PMID- 16907318
TI  - Growth-melt asymmetry in crystals and twelve-sided snowflakes.
AB  - It is in the lexicon of crystal growth that the shape of a growing crystal
      reflects the underlying microscopic architecture. Although it is known that in
      weakly nonequilibrium conditions the slowest growing orientations ultimately
      dominate the asymptotic shape, is the same true for melting? Here we observe and
      show theoretically that while the two-dimensional steady melt shapes of ice are
      bounded by six planes, these planes are not proper facets but instead are rotated
      30 degrees from the prism planes of ice. Finally, the transient melting state
      exposes 12 apparent crystallographic planes thereby differing substantially from
      the transient growth state.

PMID- 16907319
TI  - Nonequilibrium Green's function approach to phonon transport in defective carbon
      nanotubes.
AB  - We have developed a new theoretical formalism for phonon transport in
      nanostructures using the nonequilibrium phonon Green's function technique and
      have applied it to thermal conduction in defective carbon nanotubes. The
      universal quantization of low-temperature thermal conductance in carbon nanotubes
      can be observed even in the presence of local structural defects such as
      vacancies and Stone-Wales defects, since the long wavelength acoustic phonons are
      not scattered by local defects. At room temperature, however, thermal conductance
      is critically affected by defect scattering since incident phonons are scattered
      by localized phonons around the defects. We find a remarkable change from quantum
      to classical features for the thermal transport through defective carbon
      nanotubes with increasing temperature.

PMID- 16907320
TI  - Does bulk metallic glass of elemental Zr and Ti exist?
AB  - To verify the high-pressure formation of the bulk metallic glass in elemental Zr
      and Ti, which Zhang and Zhao [Nature (London) 430, 332 (2004)] and Y. Wang et al.
      [Phys. Rev. Lett. 95, 155501 (2005)] recently reported, the high-pressure states
      were investigated by our newly developed in situ angle-dispersive x-ray
      diffraction using a two-dimensional detector and x-ray transparent anvils.
      Despite the disappearance of all the Bragg peaks in the one-dimensional energy
      dispersive data, two-dimensional angle-dispersive data showed several intense
      Bragg spots even at the conditions where the amorphization was reported. This
      finding suggests that Zr and Ti do not transform into an amorphous state, but
      that their grain size becomes large, which causes the missing Bragg peaks in
      energy-dispersive data.

PMID- 16907321
TI  - Nanoscale anisotropic plastic deformation in single crystal aragonite.
AB  - The nanoscale anisotropic elastic-plastic behavior of single-crystal aragonite is
      studied using nanoindentation and tapping mode atomic force microscopy imaging.
      Force-depth curves coaxial to the axis exhibited load plateaus indicative of
      dislocation nucleation events. Plasticity on distinct slip systems was evident in
      residual topographic impressions where four pileup lobes were present after
      indentation with a conospherical probe and distinct, protruding slip bands were
      present after indentation with a Berkovich pyramidal probe. A finite element
      crystal plasticity model revealed the governing roles of the {110}<001>slip
      system family, as well as the (100)[010], (100)[001], (010)[100], (010)[001],
      (001)[100] and (001)[010] systems.

PMID- 16907322
TI  - Mechanisms of the wurtzite to rocksalt transformation in CdSe nanocrystals.
AB  - We study the pressure-driven phase transition from the four-coordinate wurtzite
      to the six-coordinate rocksalt structure in CdSe nanocrystals with molecular
      dynamics computer simulations. With an ideal gas as the pressure medium, we apply
      hydrostatic pressure to spherical and faceted nanocrystals ranging in diameter
      from 25 to 62 A. In spherical crystals, the main mechanism of the transformation
      involves the sliding of (100) planes, but depending on the specific surface
      structure we also observe a second mechanism proceeding through the flattening of
      (100) planes. In faceted crystals, the transition proceeds via a five-coordinated
      hexagonal structure, which is stabilized at intermediate pressures due to
      dominant surface energetics.

PMID- 16907323
TI  - Bond-induced ergodicity breakdown in reactive mixtures.
AB  - We have studied by inelastic x-ray scattering, at wave vectors 1 nm < or =q< or
      =15 nm(-1), the high-frequency dynamics of epoxy-amine mixtures as the monomers
      irreversibly polymerize. We find that chemical bonding, while inducing molecular
      ordering on a mesoscopic length scale, also efficiently realizes the mechanism of
      dynamical arrest described by the mode-coupling theory, as manifested by a cusp
      singularity in the behavior of the nonergodicity factor as a function of the
      number of chemical bonds. These results confront positively the mode-coupling
      theory with a new control parameter.

PMID- 16907324
TI  - Superheating and solid-liquid phase coexistence in nanoparticles with nonmelting
      surfaces.
AB  - We present a phenomenological model of melting in nanoparticles with facets that
      are only partially wet by their liquid phase. We show that in this model, as the
      solid nanoparticle seeks to avoid coexistence with the liquid, the microcanonical
      melting temperature can exceed the bulk melting point and that the onset of
      coexistence is a first-order transition. We show that these results are
      consistent with molecular dynamics simulations of aluminum nanoparticles which
      remain solid above the bulk melting temperature.

PMID- 16907325
TI  - Experimental measurement of single-wall carbon nanotube torsional properties.
AB  - We report on the characterization of nanometer-scale torsional devices based on
      individual single-walled carbon nanotubes as the spring elements. The axial shear
      moduli of the nanotubes are obtained through modeling of device reaction to
      various amounts of applied electrostatic force and are compared to theoretical
      values.

PMID- 16907326
TI  - Contact area measurements reveal loading-history dependence of static friction.
AB  - We perform quantitative measurements of the actual area of contact, A, formed by
      two rough solids that are subjected to different normal loading protocols. We
      show that microscopic motion, induced by Poisson contraction or expansion,
      produces a strong memory dependence of on the loading history with a large
      corresponding influence on the system's frictional strength. These effects,
      together with accompanying transient dynamics, are independent of humidity,
      loading rates, and material contrast across the interface.

PMID- 16907327
TI  - Orbital ordering and spin-ladder formation in La2RuO5.
AB  - The semiconductor-semiconductor transition of La2RuO5 is studied by means of
      augmented spherical wave electronic structure calculations as based on density
      functional theory and the local density approximation. This transition has lately
      been reported to lead to orbital ordering and a quenching of the local spin
      magnetic moment. Our results hint towards an orbital ordering scenario which,
      markedly different from the previously proposed scheme, preserves the local S=1
      moment at the Ru sites in the low-temperature phase. The unusual magnetic
      behavior is interpreted by the formation of spin ladders, which result from the
      structural changes occurring at the transition and are characterized by
      antiferromagnetic coupling along the rungs.

PMID- 16907328
TI  - Orbitally driven spin-singlet dimerization in S=1 La4Ru2O10.
AB  - Using x-ray absorption spectroscopy at the Ru-L2,3 edge we reveal that the Ru4+
      ions remain in the S=1 spin state across the rare 4d-orbital ordering transition
      and spin-gap formation. We find using local spin density approximation + Hubbard
      U band structure calculations that the crystal fields in the low-temperature
      phase are not strong enough to stabilize the S=0 state. Instead, we identify a
      distinct orbital ordering with a significant anisotropy of the antiferromagnetic
      exchange couplings. We conclude that La4Ru2O10 appears to be a novel material in
      which the orbital physics drives the formation of spin-singlet dimers in a quasi
      two-dimensional S=1 system.

PMID- 16907329
TI  - Quantum criticality in the cubic heavy-fermion system CeIn3-xSnx.
AB  - We report a comprehensive study of CeIn3-xSnx (0.55<or=x< or=0.8) single crystals
      close to the antiferromagnetic quantum-critical point (QCP) at xc approximately
      0.37 by means of the low-temperature thermal expansion and Gruneisen parameter.
      This system represents the first example for a cubic heavy fermion in which TN
      can be suppressed continuously down to T=0. A characteristic sign change of the
      Gruneisen parameter between the antiferromagnetic and paramagnetic states
      indicates the accumulation of entropy close to the QCP. The observed quantum
      critical behavior is compatible with the predictions of the itinerant theory for
      three-dimensional critical spin fluctuations. This has important implications for
      the role of the dimensionality in heavy-fermion QCPs.

PMID- 16907330
TI  - Current driven magnetization dynamics in helical spin density waves.
AB  - A mechanism is proposed for manipulating the magnetic state of a helical spin
      density wave using a current. It is shown that a current through a bulk metal
      with a helical spin density wave induces a spin transfer torque, which gives rise
      to a rotation of the order parameter. The use of spin transfer torque to
      manipulate the magnetization in bulk systems does not suffer from the obstacles
      seen for magnetization reversal using interface spin transfer torque in
      multilayered systems. The effect is demonstrated by a quantitative calculation of
      the current induced magnetization dynamics of a rare earth metal, Er. Finally, we
      propose a setup for experimental verification.

PMID- 16907331
TI  - Quantum Hall ferromagnetism in graphene.
AB  - Graphene is a two-dimensional carbon material with a honeycomb lattice and Dirac
      like low-energy excitations. When Zeeman and spin-orbit interactions are
      neglected, its Landau levels are fourfold degenerate, explaining the 4e2/h
      separation between quantized Hall conductivity values seen in recent experiments.
      In this Letter we derive a criterion for the occurrence of interaction-driven
      quantum Hall effects near intermediate integer values of e2/h due to charge gaps
      in broken symmetry states.

PMID- 16907332
TI  - Quasi-one-dimensional quantized states in an epitaxial Ag film on a one
      dimensional surface superstructure.
AB  - The in-plane energy dispersion of quantized states in an ultrathin Ag film formed
      on the one-dimensional (1D) surface superstructure Si(111)-(4 x 1)-In shows clear
      1D anisotropy instead of the isotropic two-dimensional free-electron-like
      behavior expected for an isolated metal film. The present photoemission results
      demonstrate that an atomic layer at the film-substrate interface can regulate the
      dimensionality of electron motion in quantum films.

PMID- 16907333
TI  - Unusual microwave response of dirac quasiparticles in graphene.
AB  - Recent experiments have proven that the quasiparticles in graphene obey a Dirac
      equation. Here we show that microwaves are an excellent probe of their unusual
      dynamics. When the chemical potential is small, the intraband response can
      exhibit a cusp around zero frequency Omega and this unusual line shape changes to
      Drude-like by increasing the chemical potential |mu|, with width linear in mu.
      The interband contribution at T=0 is a constant independent of Omega with a lower
      cutoff at 2mu. Distinctly different behavior occurs if interaction-induced
      phenomena in graphene cause an opening of a gap Delta. At a large magnetic field
      B, the diagonal and Hall conductivities at small Omega become independent of B
      but remain nonzero and show a structure associated with the lowest Landau level.
      This occurs because in the Dirac theory the energy of this level, E0 = +/-Delta,
      is field independent in sharp contrast to the conventional case.

PMID- 16907334
TI  - Doping dependence of bilayer resonant spin excitations in (Y, Ca)Ba2Cu3O6+x.
AB  - Resonant magnetic modes with odd and even symmetries were studied by inelastic
      neutron scattering experiments in the bilayer high-Tc superconductor Y1
      xCa+Ba2Cu3O6+y over a wide doping range. The threshold of the spin excitation
      continuum in the superconducting state, deduced from the energies and spectral
      weights of both modes, is compared with the superconducting d-wave gap, deduced
      from electronic Raman scattering in the B1g symmetry on the same samples. Above a
      critical doping level of delta approximately =0.19, both mode energies and the
      continuum threshold coincide. We find a simple scaling relationship between the
      characteristic energies and spectral weights of both modes, which indicates that
      the resonant modes are bound states in the superconducting energy gap, as
      predicted by the spin-exciton model of the resonant mode.

PMID- 16907335
TI  - Charge order, metallic behavior, and superconductivity in La2-xBaxCuO4 with
      x=1/8.
AB  - The ab-plane optical properties of a cleaved single crystal of La2-xBaxCuO4 for
      x=1/8 (Tc approximately =2.4 K) have been measured over a wide frequency and
      temperature range. The low-frequency conductivity is Drude-like and shows a
      metallic response with decreasing temperature. However, below approximately =60
      K, corresponding to the onset of charge-stripe order, there is a rapid loss of
      spectral weight below about 40 meV. The behavior is quite different from that
      typically associated with the pseudogap in the normal state of the cuprates.
      Instead, the gapping of the normal-state single-particle excitations looks
      surprisingly similar to that observed in superconducting La2-xSrxCuO4, including
      the presence of a residual Drude peak with reduced weight.

PMID- 16907336
TI  - Spin-wave dispersion in orbitally ordered La1/2Sr3/2MnO4.
AB  - The magnon dispersion in the charge, orbital, and spin ordered phase in
      La1/2Sr3/2MnO4 has been studied by means of inelastic neutron scattering. We find
      excellent agreement with a magnetic interaction model based on the CE-type
      superstructure. The magnetic excitations are dominated by ferromagnetic exchange
      parameters revealing a nearly one-dimensional character at high energies. The
      strong ferromagnetic interaction in the charge or orbital ordered phase appears
      to be essential for the capability of manganites to switch between metallic and
      insulating phases.

PMID- 16907337
TI  - Dynamical spin structure factor for the anisotropic spin-1/2 Heisenberg chain.
AB  - The longitudinal spin structure factor for the XXZ-chain at small wave vector q
      is obtained using Bethe ansatz, field theory methods, and the density matrix
      renormalization group. It consists of a peak with a peculiar, non-Lorentzian
      shape and a high-frequency tail. We show that the width of the peak is
      proportional to q2 for finite magnetic field compared to q3 for a zero field. For
      the tail we derive an analytic formula without any adjustable parameters and
      demonstrate that the integrability of the model directly affects the line shape.

PMID- 16907338
TI  - Quantum criticality in an organic magnet.
AB  - Exchange interactions between S=1/2 sites in piperazinium hexachlorodicuprate
      produce a frustrated bilayer magnet with a singlet ground state. We have
      determined the field-temperature phase diagram by high field magnetization and
      neutron scattering experiments. There are two quantum critical points: Hc1=7.5 T
      separates a quantum paramagnet phase from a three dimensional,
      antiferromagnetically ordered state while Hc2=37 marks the onset of a fully
      polarized state. The ordered phase, which we describe as a magnon Bose-Einstein
      condensate (BEC), is embedded in a quantum critical regime with short range
      correlations. A low temperature anomaly in the BEC phase boundary indicates that
      additional low energy features of the material become important near Hc1.

PMID- 16907339
TI  - Intrinsic distribution of magnetic anisotropy in thin films probed by patterned
      nanostructures.
AB  - We demonstrate that the switching field distribution (SFD) in arrays of 50 nm to
      5 microm Co/Pd elements, with perpendicular anisotropy, can be explained by a
      distribution of intrinsic anisotropy rather than any fabrication related effects.
      Further, simulations of coercivity and SFD versus element size allow the
      distribution of intrinsic anisotropy to be quantified in highly exchanged coupled
      thin films where the reversal mechanism is one of nucleation followed by rapid
      domain wall motion.

PMID- 16907340
TI  - Perpendicular magnetic anisotropy induced by tetragonal distortion of FeCo alloy
      films grown on Pd(001).
AB  - We grew tetragonally distorted FexCo1-x alloy films on Pd(001). Theoretical first
      principles calculations for such films predicted a high saturation magnetization
      and a high uniaxial magnetic anisotropy energy for specific values of the lattice
      distortion c/a and the alloy composition x. The magnetic anisotropy was
      investigated using the magneto-optical Kerr effect. An out-of-plane easy axis of
      magnetization was observed for Fe0.5Co0.5 films in the thickness range of 4 to 14
      monolayers. The magnetic anisotropy energy induced by the tetragonal distortion
      is estimated to be almost 2 orders of magnitude larger than the value for bulk
      FeCo alloys. Using LEED Kikuchi patterns, a change of the easy axis of
      magnetization can be related to a decrease of the tetragonal distortion with
      thickness.

PMID- 16907341
TI  - Raman active phonons of identified semiconducting single-walled carbon nanotubes.
AB  - The resonant Raman spectra of (n, m) semiconducting single-walled carbon
      nanotubes, unambiguously identified from their electron diffraction patterns,
      have been measured. The diameter dependence of the frequency of the tangential
      modes with A symmetry has been obtained in the diameter range from 1.4 to 2.5 nm.
      The comparison between the excitation energies and the calculated transition
      energies allowed us to determine precisely the values of the Es33 and Es44
      transition energies. Finally, in the debate concerning the dominant process at
      the origin of the first-order Raman scattering in single-walled carbon nanotubes
      (single resonance process or double resonance process), our results are well
      understood in the framework of a single resonance process.

PMID- 16907342
TI  - Microwave transmission of a compound metal grating.
AB  - An array of subwavelength slits in a metallic substrate supports a series of
      Fabry-Perot-like resonances, where each harmonic results in a transmission peak.
      Addition of extra slits per period yields a compound grating with a structure
      factor associated with the basis. In this study each repeat period is comprised
      of a central slit flanked by a pair of narrower slits. It supports three
      resonances for every Fabry-Perot-like solution. New and useful insight into this
      phenomenon is gained by describing each of the modes in terms of the band
      structure of diffractively coupled surface waves.

PMID- 16907343
TI  - Static nuclear spin polarization induced in a liquid by a rotating magnetic
      field.
AB  - We demonstrate that protons in a liquid acquire a static polarization
      perpendicular to the plane of a rotating magnetic field. The rotating field was
      reduced adiabatically to zero, transforming the static polarization in the
      rotating frame to the laboratory frame. The application of a small magnetic field
      perpendicular to the polarization induced a free induction decay (FID) that was
      detected by a superconducting quantum interference device. The results agree with
      the predictions of the modified Bloch equations. The FID remained observable in
      the presence of magnetic material, suggesting that this technique may find
      practical applications.

PMID- 16907344
TI  - Relationship between structural and stress relaxation in a block-copolymer melt.
AB  - The relationship between structural relaxation on molecular length scales and
      macroscopic stress relaxation was explored in a disordered block-copolymer melt.
      Experiments show that the structural relaxation time, measured by x-ray photon
      correlation spectroscopy is larger than the terminal stress relaxation time,
      measured by rheology, by factors as large as 100. We demonstrate that the
      structural relaxation data are dominated by the diffusion of intact micelles
      while the stress relaxation data are dominated by contributions due to disordered
      concentration fluctuations.

PMID- 16907345
TI  - Crystallization of a quasi-two-dimensional granular fluid.
AB  - We experimentally investigate the crystallization of a uniformly heated quasi-2D
      granular fluid as a function of the filling fraction. Our experimental results
      for the Lindemann melting criterion, the radial distribution function, the bond
      order parameter, and the statistics of topological changes at the particle level
      are the same as those found in simulations of equilibrium hard disks. This direct
      mapping suggests that the study of equilibrium systems can be effectively applied
      to study nonequilibrium steady states such as those found in our driven and
      dissipative granular system.

PMID- 16907346
TI  - Velocity autocorrelations and viscosity renormalization in sheared granular
      flows.
AB  - The decay of the velocity autocorrelation function in a sheared granular flow is
      analyzed in the limit where the wavelength of fluctuations is larger than the
      "conduction length," so that energy is a nonconserved variable. The decay of the
      velocity autocorrelation function is much faster than that in a fluid at
      equilibrium for which energy is a conserved variable. Specifically, the
      autocorrelation function in a sheared granular flow decays proportional to t-3 in
      2D and t-9/2 in 3D, in contrast with the decay proportional to t-1 in 2D and t
      3/2 in 3D for a fluid at equilibrium. The renormalization of the viscosity due to
      mode coupling is evaluated using this form of the decay of the autocorrelation
      function. It is found that the logarithmic divergence in the viscosity in 2D, and
      the divergence of the Burnett coefficients in 3D, which is characteristic of a
      fluid of elastic particles at equilibrium, is absent in a sheared granular flow.

PMID- 16907347
TI  - Time-invariant person-specific frequency templates in human brain activity.
AB  - The various human brain tasks are performed at different locations and time
      scales. Yet, we discovered the existence of time-invariant (above an essential
      time scale) partitioning of the brain activity into personal state-specific
      frequency bands. For that, we perform temporal and ensemble averaging of best
      wavelet packet bases from multielectrode electroencephalogram recordings. These
      personal frequency bands provide new templates for quantitative analyses of brain
      function, e.g., normal versus epileptic activity.

PMID- 16907348
TI  - Spatially synchronous extinction of species under external forcing.
AB  - More than 99% of the species that ever existed on the surface of the Earth are
      now extinct and their extinction on a global scale has been a puzzle. One may
      think that a species under an external threat may survive in some isolated
      locations leading to the revival of the species. Using a general model we show
      that, under a common external forcing, the species with a quadratic saturation
      term first undergoes spatial synchronization and then extinction. The effect can
      be observed even when the external forcing acts only on some locations provided
      the dynamics contains a synchronizing term. Absence of the quadratic saturation
      term can help the species to avoid extinction.

PMID- 16907349
TI  - Enhanced ordering of interacting filaments by molecular motors.
AB  - We theoretically study the cooperative behavior of cytoskeletal filaments in
      motility assays in which immobilized motor proteins bind the filaments to
      substrate surfaces and actively pull them along these surfaces. Because of the
      mutual exclusion of the filaments, the coupled dynamics of filaments, motor
      heads, and motor tails leads to a nonequilibrium phase transition which
      generalizes the isotropic-nematic phase transition of the corresponding
      equilibrium system, the hard-rod fluid. Langevin dynamics simulations show that
      the motor activity enhances the tendency for nematic ordering. We develop a
      quantitative theory for the location of the phase boundary as a function of motor
      density. At high detachment forces of motors, we also observe filament clusters
      arising from blocking effects.

PMID- 16907350
TI  - Microstructure and rheology near an attractive colloidal glass transition.
AB  - Microstructure and rheological properties of a thermally reversible short-ranged
      attractive colloidal system are studied in the vicinity of the attractive glass
      transition line. At high volume fractions, the static structure factor changes
      very little but the low frequency shear moduli varies over several orders of
      magnitude across the transition. From the frequency dependence of shear moduli,
      fluid-attractive glass and repulsive glass-attractive glass transitions are
      identified.

PMID- 16907351
TI  - Chiral nematic phase of suspensions of rodlike viruses: left-handed phase
      helicity from a right-handed molecular helix.
AB  - We report a study on charged, filamentous virus called M13, whose suspensions in
      water exhibit a chiral nematic (cholesteric) phase. In spite of the right-handed
      helicity of the virus, a left-handed phase helicity is found, with a cholesteric
      pitch which increases with temperature and ionic strength. Several sources of
      chirality can be devised in the system, ranging from the subnanometer to the
      micrometer length scale. Here an explanation is proposed for the microscopic
      origin of the cholesteric organization, which arises from the helical arrangement
      of coat proteins on the virus surface. The phase organization is explained as the
      result of the competition between contributions of opposite handedness, deriving
      from best packing of viral particles and electrostatic interparticle repulsions.
      This hypothesis is supported by calculations based on a coarse-grained
      representation of the virus.

PMID- 16907352
TI  - Comment on "Delayed fracture in porous media".

PMID- 16907353
TI  - Comment on "Spectroscopic evidence for multiple order parameters in the heavy
      fermion superconductor CeCoIn5".

PMID- 16907354
TI  - Comment on "Spectroscopic evidence for multiple order parameter components in the
      heavy fermion superconductor CeCoIn5".

PMID- 16907356
TI  - Entropic lattice Boltzmann models for hydrodynamics in three dimensions.
AB  - Efficient, nonlinearly stable entropic lattice Boltzmann models for computational
      fluid dynamics are presented. A new method of fast evaluation of equilibria to
      machine precision is proposed. Analytical solution is found for the collision
      step which guarantees stability and thermodynamic consistency of the scheme. As
      an example, a novel 15-velocity lattice Boltzmann model is derived and validated
      with a simulation of a three-dimensional backward-facing step flow.

PMID- 16907357
TI  - Level density of a Fermi gas: average growth and fluctuations.
AB  - We compute the level density of a two-component Fermi gas as a function of the
      number of particles, angular momentum, and excitation energy. The result includes
      smooth low-energy corrections to the leading Bethe term (connected to a
      generalization of the partition problem and Hardy-Ramanujan formula) plus
      oscillatory corrections that describe shell effects. When applied to nuclear
      level densities, the theory provides a unified formulation valid from low-lying
      states up to levels entering the continuum. The comparison with experimental data
      from neutron resonances gives excellent results.

PMID- 16907358
TI  - Six-axis inertial sensor using cold-atom interferometry.
AB  - We have developed an atom interferometer providing a full inertial base. This
      device uses two counterpropagating cold-atom clouds that are launched in strongly
      curved parabolic trajectories. Three single Raman beam pairs, pulsed in time, are
      successively applied in three orthogonal directions leading to the measurement of
      the three axis of rotation and acceleration. In this purpose, we introduce a new
      atom gyroscope using a butterfly geometry. We discuss the present sensitivity and
      the possible improvements.

PMID- 16907359
TI  - Vortices in attractive Bose-Einstein condensates in two dimensions.
AB  - The form and stability of quantum vortices in Bose-Einstein condensates with
      attractive atomic interactions is elucidated. They appear as ring bright
      solitons, and are a generalization of the Townes soliton to nonzero winding
      number m. An infinite sequence of radially excited stationary states appear for
      each value of m, which are characterized by concentric matter-wave rings
      separated by nodes, in contrast to repulsive condensates, where no such set of
      states exists. It is shown that robustly stable as well as unstable regimes may
      be achieved in confined geometries, thereby suggesting that vortices and their
      radial excited states can be observed in experiments on attractive condensates in
      two dimensions.

PMID- 16907360
TI  - Braid group, gauge invariance, and topological order.
AB  - Topological order in two-dimensional systems is studied by combining the braid
      group formalism with a gauge invariance analysis. We show that flux insertions
      (or large gauge transformations) pertinent to the toroidal topology induce
      automorphisms of the braid group, giving rise to a unified algebraic structure
      that characterizes the ground-state subspace and fractionally charged, anyonic
      quasiparticles. Minimal ground-state degeneracy is derived without assuming any
      relation between quasiparticle charge and statistics. We also point out that
      noncommutativity between large gauge transformations is essential for the
      topological order in the fractional quantum Hall effect.

PMID- 16907361
TI  - Interaction-driven real-space condensation.
AB  - We study real-space condensation in a broad class of stochastic mass transport
      models. We show that the steady state of such models has a pair-factorized form
      which generalizes the standard factorized steady states. The condensation in this
      class of models is driven by interactions which give rise to a spatially extended
      condensate that differs fundamentally from the previously studied examples. We
      present numerical results as well as a theoretical analysis of the condensation
      transition and show that the criterion for condensation is related to the binding
      unbinding transition of solid-on-solid interfaces.

PMID- 16907362
TI  - Theory of cooling by flow through narrow pores.
AB  - We consider the possibility of adding a stage to a dilution refrigerator to
      provide additional cooling by "filtering out" hot atoms. Three methods are
      considered: (1) effusion, where holes having diameters larger than a mean-free
      path allow atoms to pass through easily; (2) particle waveguidelike motion using
      very narrow channels that greatly restrict the quantum states of the atoms in a
      channel; (3) wall-limited diffusion through channels, in which the wall
      scattering is disordered so that local density equilibrium is established in a
      channel. We assume that channel dimensions are smaller than the mean-free path
      for atom-atom interactions. The particle waveguide and the wall-limited diffusion
      methods using channels on order of the de Broglie wavelength give cooling. Recent
      advances in nanofilters give this method some hope of being practical.

PMID- 16907363
TI  - Coherent control of vacuum squeezing in the gravitational-wave detection band.
AB  - We propose and demonstrate a coherent control scheme for stable phase locking of
      squeezed vacuum fields. We focus on sideband fields at frequencies from 10 Hz to
      10 kHz, which is a frequency regime of particular interest in gravitational-wave
      detection and for which conventional control schemes have failed so far. A vacuum
      field with broadband squeezing covering this entire band was produced using
      optical parametric oscillation and characterized with balanced homodyne
      detection. The system was stably controlled over long periods utilizing two
      coherent but frequency shifted control fields. In order to demonstrate the
      performance of our setup the squeezed field was used for a nonclassical
      sensitivity improvement of a Michelson interferometer at audio frequencies.

PMID- 16907364
TI  - Sigma coupling to photons: hidden scalar in gammagamma --> pi0pi0.
AB  - There has long been speculation about the nature of the sigma resonance. For
      three decades Jaffe has argued for a tetraquark composition, while others have
      claimed it is largely a glueball. A key pointer to its nature is its coupling to
      two photons. Consequently, there have been recent proposals to observe this
      important scalar hiding in gammagamma--> pi0pi0. We show here that the sigma is
      already crouching in this cross section exactly as measured 20 years ago. What is
      new is that precise knowledge of the position of the sigma pole, provided by the
      analysis of the Roy equations, now allows its two photon coupling to be
      accurately fixed. Its two photon width is found to be (4.1 +/- 0.3) keV, a value
      far too large for a wholly gluonic, or even a tetraquark, state.

PMID- 16907365
TI  - Nucleon-nucleon scattering from fully dynamical lattice QCD.
AB  - We present results of the first fully dynamical lattice QCD determination of
      nucleon-nucleon scattering lengths in the 1S0 channel and 3S1 - 3D1 coupled
      channels. The calculations are performed with domain-wall valence quarks on the
      MILC staggered configurations with a lattice spacing of b = 0.125 fm in the
      isospin-symmetric limit, and in the absence of electromagnetic interactions.

PMID- 16907367
TI  - Overlap Dirac operator at nonzero chemical potential and random matrix theory.
AB  - We show how to introduce a quark chemical potential in the overlap Dirac
      operator. The resulting operator satisfies a Ginsparg-Wilson relation and has
      exact zero modes. It is no longer gamma5 Hermitian, but its nonreal eigenvalues
      still occur in pairs. We compute the spectral density of the operator on the
      lattice and show that, for small eigenvalues, the data agree with analytical
      predictions of non-Hermitian chiral random matrix theory for both trivial and
      nontrivial topology. We also explain an observed change in the number of zero
      modes as a function of chemical potential.

PMID- 16907368
TI  - Energy dependence of directed flow over a wide range of pseudorapidity in Au + Au
      collisions at the BNL Relativistic Heavy Ion Collider.
AB  - We report on measurements of directed flow as a function of pseudorapidity in Au
      + Au collisions at energies of square root of SNN = 19.6, 62.4, 130 and 200 GeV
      as measured by the PHOBOS detector at the BNL Relativistic Heavy Ion Collider.
      These results are particularly valuable because of the extensive, continuous
      pseudorapidity coverage of the PHOBOS detector. There is no significant
      indication of structure near midrapidity and the data surprisingly exhibit
      extended longitudinal scaling similar to that seen for elliptic flow and charged
      particle pseudorapidity density.

PMID- 16907369
TI  - Giant dipole resonance in the hot and thermalized 132Ce nucleus: damping of
      collective modes at finite temperature.
AB  - The gamma decay of the giant dipole resonance (GDR) in the 132Ce compound nucleus
      with temperature up to approximately 4 MeV has been measured, using the reaction
      64Ni + 68Zn at E(beam) = 300, 400, and 500 MeV. The gamma and charged particles
      measured in coincidence with recoils are consistent with a fully equilibrated
      compound nucleus emission. The GDR width, obtained with the statistical model
      analysis, is found to increase almost linearly with temperature. This increase is
      rather well reproduced within a model including thermal shape fluctuations and
      the lifetime of the compound nucleus.

PMID- 16907370
TI  - Attosecond pulse trains generated using two color laser fields.
AB  - We investigate the spectral and temporal structure of high harmonic emission from
      argon exposed to an infrared laser field and its second harmonic. For a wide
      range of generating conditions, trains of attosecond pulses with only one pulse
      per infrared cycle are generated. The synchronization necessary for producing
      such trains ensures that they have a stable pulse-to-pulse carrier envelope
      phase, unlike trains generated from one color fields, which have two pulses per
      cycle and a pi phase shift between consecutive pulses. Our experiment extends the
      generation of phase stabilized few cycle pulses to the extreme ultraviolet
      regime.

PMID- 16907371
TI  - Improved theory of helium fine structure.
AB  - Improved theoretical predictions for the fine-structure splitting of 2(3)PJ
      levels in helium are obtained by the calculation of contributions of order alpha5
      Ry. New results for transition frequencies nu(01) = 29616943.01(17) kHz and
      nu(12) = 2291161.13(30) kHz disagree significantly with the experimental values,
      indicating an outstanding problem in bound state QED.

PMID- 16907372
TI  - Above threshold Coulomb explosion of molecules in intense laser pulses.
AB  - We have measured and explained a new mechanism of molecular ionization near the
      appearance intensity that produces a sequence of peaks in the nuclear kinetic
      energy spectrum separated by the photon energy. Our interpretation is based on an
      internally consistent model for the nuclear motion during an intense laser pulse.
      Within this model, the same concepts and language can be used for both
      dissociation and ionization, leading to a more unified understanding of the
      dynamics.

PMID- 16907373
TI  - Light transport in cold atoms and thermal decoherence.
AB  - We use the coherent backscattering interference effect to investigate
      experimentally and theoretically how coherent transport of light inside a cold
      atomic vapor is affected by the residual motion of atomic scatterers. As the
      temperature of the atomic cloud increases, the interference contrast decreases
      dramatically. This emphasizes the role of motion-induced decoherence for resonant
      scatterers even in the sub-Doppler regime of temperature. We derive analytical
      expressions for the corresponding coherence time.

PMID- 16907374
TI  - Exact-exchange spin-current density-functional theory.
AB  - A spin-current density-functional theory (SCDFT) is introduced, which takes into
      account the currents of the spin density and thus currents of the magnetization
      in addition to the electron density, the noncollinear spin density, and the
      density current, which are considered in standard current-spin-density-functional
      theory. An exact-exchange Kohn-Sham formalism based on SCDFT is presented, which
      represents a general framework for the treatment of magnetic and spin properties.
      As an illustration, an oxygen atom in a magnetic field is treated with the new
      approach.

PMID- 16907375
TI  - Importance of nonresonant scattering in low-energy dissociative electron
      attachment to molecular hydrogen.
AB  - A central premise of nearly all theories of dissociative electron attachment is
      that this process is resonance driven. Neglect of nonresonant scattering,
      although appropriate for electron-molecule systems with narrow (long-lived)
      resonances, is problematic for the e-H2 system, which has one of the broadest
      known resonances. Using the nonadiabatic phase-matrix method we have found that
      at energies from threshold to 6 eV contributions from nonresonant scattering to
      cross sections to dissociative attachment to in its ground vibrational and
      electronic state exceed 60%. Comparison of theoretical and experimental cross
      sections argue strongly for further efforts to resolve the considerable remaining
      discrepancies over this most elementary rearrangement process.

PMID- 16907376
TI  - Speckle patterns with atomic and molecular de Broglie waves.
AB  - We have developed a nozzle source that delivers a continuous beam of atomic
      helium or molecular hydrogen having a high degree of transverse coherence and
      with adequate optical brightness to enable new kinds of experiments. Using this
      source we have measured single slit diffraction patterns and the first ever
      speckle-diffraction patterns using atomic and molecular de Broglie waves. Our
      results suggest fruitful application of coherent matter beams in dynamic
      scattering and diffractive imaging at short wavelength and with extreme surface
      sensitivity.

PMID- 16907377
TI  - Deterministic single photons via conditional quantum evolution.
AB  - A source of deterministic single photons is proposed and demonstrated by the
      application of a measurement-based feedback protocol to a heralded single-photon
      source consisting of an ensemble of cold rubidium atoms. Our source is stationary
      and produces a photoelectric detection record with sub-Poissonian statistics.

PMID- 16907378
TI  - Do solitonlike self-similar waves exist in nonlinear optical media?
AB  - We show analytically that bright and dark spatial self-similar waves can
      propagate in graded-index amplifiers exhibiting self-focusing or self-defocusing
      Kerr nonlinearities. The intensity profiles of the novel waves are identical with
      those of fundamental bright or dark spatial solitons supported by homogeneous
      passive waveguides with the same type of nonlinearity. Thus, we reveal a
      previously unnoticed connection between spatial solitons and self-similar waves.
      We also suggest that the discovered self-similar waves can be used in a promising
      scheme for the amplification and focusing of spatial solitons in future all
      optical networks.

PMID- 16907379
TI  - Generation of light in media with a random distribution of nonlinear domains.
AB  - We show that the second order nonlinear generation of light, a process that it is
      assumed to require highly ordered materials, is also possible in structures of
      randomly oriented nonlinear domains. We explain theoretically why in such
      disordered structures the efficiency of the nonlinear generation of light grows
      linearly with the number of domains. Moreover, a higher degree of disorder,
      obtained when the dispersion is made very large, has no negative effect for the
      nonlinear light generation. In such conditions, light generation is shown to be
      equally efficient for any average size of the domains and also to grow linearly
      with respect to the number of domains.

PMID- 16907380
TI  - Transient development of backward stimulated Raman and Brillouin scattering on a
      picosecond time scale measured by subpicosecond thomson diagnostic.
AB  - The excitation and the relaxation of the plasma waves and ion acoustic waves
      (IAW), respectively, driven by stimulated Raman (SRS) and Brillouin (SBS)
      backscatterings have been experimentally investigated with short-pulse lasers.
      The spectra have been obtained with a 0.3 ps time resolution. It is shown that
      SRS develops before SBS and suddenly decays around the peak of the pump, as the
      IAW reaches saturation. On this short time scale, electron kinetic effects play a
      major role for SRS saturation, contrary to ion dynamics. These results are
      supported by particle-in-cell simulations.

PMID- 16907381
TI  - Current-driven rotating-kink mode in a plasma column with a non-line-tied free
      end.
AB  - First experimental measurements are presented for the kink instability in a
      linear plasma column which is insulated from an axial boundary by finite sheath
      resistivity. An instability threshold below the classical Kruskal-Shafranov
      threshold, axially asymmetric mode structure, and rotation are observed. These
      are accurately reproduced by a recent kink theory, which includes axial plasma
      flow and one end of the plasma column that is free to move due to a non-line-tied
      boundary condition.

PMID- 16907382
TI  - Electrical breakdown in helium cells at low temperature.
AB  - Electrical breakdown of partially filled helium cells below 0.5 K is shown to be
      the result of Penning ionization of metastable triplet helium excimers bound to
      the surface of the liquid.

PMID- 16907383
TI  - Isoconfigurational elastic constants and liquid fragility of a bulk metallic
      glass forming alloy.
AB  - Samples of Zr(46.25)Ti(8.25)Cu(7.5)Ni(10)Be(27.5) were isothermally annealed and
      quenched near the glass transition temperature and studied by the pulse-echo
      overlap technique. The shear modulus G of the samples shows a strong reversible
      dependence on annealing temperatures and, thus, on the specific configurational
      potential energy of the equilibrium liquid. The low-T dependence of G of the
      configurationally frozen glasses shows linear temperature dependence as expected
      by Debye-Gruneisen theory. The T dependence of G in the liquid state is directly
      related to the viscosity and fragility of the liquid.

PMID- 16907366
TI  - Measurement of the Bc+ meson lifetime using the decay mode Bc+ --> J/Psie+nue.
AB  - We present a measurement of the Bc+ meson lifetime in the decay mode Bc+ -->
      J/Psie+nue using the Collider Detector at Fermilab II detector at the Fermilab
      Tevatron Collider. From a sample of about of 360 pb(-1) of pp collisions at
      square root of s = 1.96 TeV, we reconstruct J/Psie+ pairs with invariant mass in
      the kinematically allowed range 4< M(J/Psie) < 6 GeV/c2. A fit to the decay
      length distribution of 238 signal events yields a measured Bc+ meson lifetime of
      0.463(-0.065)(+0.073)(stat) +/- 0.036(syst) ps.

PMID- 16907384
TI  - Magnetically induced immiscibility in the Ising model of FeCr stainless steel.
AB  - The iron-chromium alloy system has an unexplained anomaly: although there is a
      broad miscibility gap it appears to be favorable for chromium to dissolve in
      iron. This is consistent with ab initio calculation, but no simpler physically
      intuitive picture has been presented. Here it is shown that the Ising model,
      based on the bcc lattice with antiferromagnetic and ferromagnetic species, has
      the potential to exhibit similar behavior, with a skew miscibility gap arising
      from the solubility of antiferromagnetic species on nonadjacent sites. Essential
      characteristics of stainless steel (high Cr solubility and surface segregation)
      are correctly reproduced. Under some conditions, magnetization increases with
      temperature. The equilibrium miscibility gap due to mixed magnetism and
      segregation-driven positive dM/dT are fundamental features of the bcc Ising model
      itself, not just FeCr.

PMID- 16907385
TI  - Hydration and distribution of ions at the mica-water interface.
AB  - Molecular-scale structures of mica surfaces in electrolyte solutions reveal how
      ion and interfacial hydration control cation adsorption. Key differences are
      obtained for Rb+and Sr2+ using resonant anomalous x-ray reflectivity: Rb+ adsorbs
      in a partially hydrated state and incompletely compensates the surface charge,
      but Sr2+ adsorbs in both fully and partially hydrated states while achieving full
      charge compensation. These differences are driven by balancing the energy cost of
      disrupting ion and interface hydration with the electrostatic attraction between
      the cation and charged surface.

PMID- 16907386
TI  - Scaling and universality of roughening in thermal oxidation of Si(001).
AB  - By analyzing atomic force microscopy images, we derive a continuum equation that
      quantitatively explains the roughening at the Si(001)-SiO2 interface during
      thermal oxidation at the temperature at 1200 degrees C in an Ar atmosphere
      containing a small fraction of O2. We also show that there is a phase transition
      in the universality class from a disordered to step-terrace structure at the
      interface at oxidation temperatures between 1150 and 1380 degrees C with the
      miscut angle of the substrate as the scaling parameter.

PMID- 16907387
TI  - Identification of nanoscale dissipation processes by dynamic atomic force
      microscopy.
AB  - Identification of energy-dissipation processes at the nanoscale is demonstrated
      by using amplitude-modulation atomic force microscopy. The variation of the
      energy dissipated on a surface by a vibrating tip as a function of its
      oscillation amplitude has a shape that singles out the dissipative process
      occurring at the surface. The method is illustrated by calculating the energy
      dissipation curves for surface energy hysteresis, long-range interfacial
      interactions and viscoelasticity. The method remains valid with independency of
      the amount of dissipated energy per cycle, from 0.1 to 50 eV. The agreement
      obtained between theory and experiments performed on silicon and polystyrene
      validates the method.

PMID- 16907388
TI  - Probing non-Abelian statistics with quasiparticle interferometry.
AB  - We examine interferometric experiments in systems that exhibit non-Abelian
      braiding statistics, expressing outcomes in terms of the modular S-matrix. In
      particular, this result applies to fractional quantum Hall interferometry, and we
      give a detailed treatment of the Read-Rezayi states, providing explicit
      predictions for the recently observed nu = 12/5 plateau.

PMID- 16907389
TI  - Magnetic metastability in tetrahedrally bonded magnetic III-nitride
      semiconductors.
AB  - Results of density-functional calculations for isolated transition metal (TM = V,
      Cr, Mn, Fe, Co, Ni on cation sites) doped GaN demonstrate a novel magnetic
      metastability in dilute magnetic semiconductors. In addition to the expected high
      spin ground states (4muB/Mn and 5muB/Fe), there are also metastable low spin
      states (0muB/Mn and 1muB/Fe)--a phenomenon that can be explained in simple terms
      on the basis of the ligand field theory. The transition between the high spin and
      low spin states corresponds to an intraionic transfer of two electrons between
      the t2 and e orbitals, accompanied by a spin-flip process. The results suggest
      that TM-doped wideband semiconductors (such as GaN and AlN) may present a new
      type of light-induced spin-crossover material.

PMID- 16907390
TI  - Quantum melting of the hole crystal in the spin ladder of Sr(14-x)CaxCu24O41.
AB  - We have used resonant soft x-ray scattering to study the effects of
      discommensuration on the hole Wigner crystal (HC) in the spin ladder Sr(14
      x)CaxCu24O41 (SCCO). As the hole density is varied the HC forms only with the
      commensurate wave vectors L(L) = 1/5 and L(L) = 1/3; for incommensurate values it
      "melts." A simple scaling between L(L) and temperature is observed, tau1/3/tau1/5
      = 5/3, indicating an inverse relationship between the interaction strength and
      wavelength. Our results suggest that SCCO contains hole pairs that are
      crystallized through an interplay between lattice commensuration and Coulomb
      repulsion, reminiscent of the "pair density wave" scenario.

PMID- 16907391
TI  - Destruction of the small Fermi surfaces in NaxCoO2 by disorder.
AB  - We show using density functional calculations that the small e'g Fermi surfaces
      in NaxCoO2 are destroyed by Na disorder. This provides a means to resolve the
      prediction of these sections in band structure calculations with their
      nonobservation in angle resolved photoemission experiments.

PMID- 16907392
TI  - Chemically induced conductance switching in carbon nanotube circuits.
AB  - The chemical reactivity of carbon nanotubes in H2SO4 is investigated using
      individual, single-walled carbon nanotubes (SWNTs) incorporated into electronic
      devices. Exploiting the device conductance as a sensitive indicator of chemical
      reactions, discrete oxidation and reduction events can be clearly observed.
      During oxidation, a SWNT opens circuits to a nanometer-scale tunnel junction with
      residual conduction similar to Frenkel-Poole charge emission. When
      electrochemically reduced, a SWNT returns to its original conductance. This redox
      cycle can be repeated many times, suggesting a novel chemical method of
      reversibly switching SWNT conductivity.

PMID- 16907393
TI  - Full counting statistics for the Kondo dot in the unitary limit.
AB  - We calculate the charge transfer probability distribution function chi(lambda)
      for the Kondo dot in the strong-coupling limit within the framework of the
      Nozieres-Fermi-liquid theory of the Kondo effect. At zero temperature, the ratio
      of the moments Cn of the charge distribution to the backscattering current Ibs
      follows a universal law Cn/2Ibs = (-1)n(1+2n)/6. The functional form of
      chi(lambda) is consistent with tunneling of electrons and, possibly, electron
      pairs. We then discuss the crossover behavior of chi(lambda) from weak to strong
      Coulomb repulsion in the underlying Anderson impurity model and relate this to
      the existing results. Finally, we extend our analysis to the case of finite
      temperatures.

PMID- 16907394
TI  - Strong suppression of weak localization in graphene.
AB  - Low-field magnetoresistance is ubiquitous in low-dimensional metallic systems
      with high resistivity and well understood as arising due to quantum interference
      on self-intersecting diffusive trajectories. We have found that in graphene this
      weak-localization magnetoresistance is strongly suppressed and, in some cases,
      completely absent. The unexpected observation is attributed to mesoscopic
      corrugations of graphene sheets which can cause a dephasing effect similar to
      that of a random magnetic field.

PMID- 16907395
TI  - Signatures of a noise-induced quantum phase transition in a mesoscopic metal
      ring.
AB  - We study a mesoscopic ring with an inline quantum dot threaded by an Aharonov
      Bohm flux. Zero-point fluctuations of the electromagnetic environment
      capacitively coupled to the ring, with omega(s) spectral density, can suppress
      tunneling through the dot, resulting in a quantum phase transition from an
      unpolarized to a polarized phase. We show that robust signatures of such a
      transition can be found in the response of the persistent current in the ring to
      the external flux as well as to the bias between the dot and the arm. Particular
      attention is paid to the experimentally relevant cases of Ohmic (s = 1) and sub
      Ohmic (s = 1/2) noise.

PMID- 16907396
TI  - Trapping excitons in a two-dimensional in-plane harmonic potential: experimental
      evidence for equilibration of indirect excitons.
AB  - We have trapped a gas of long-lifetime, high-mobility excitons in an in-plane
      harmonic potential. Trapping is an important step toward the goal of a controlled
      Bose-Einstein condensate of excitons. We show that the repulsive interaction
      between the excitons plays a dominant role in the behavior of the excitons, in
      contrast with the weak interactions in atomic gases. We show that under proper
      conditions the excitons thermalize in the trap to a well-defined equilibrium
      spatial distribution.

PMID- 16907397
TI  - Evidence for macroscopic quantum tunneling of phase slips in long one-dimensional
      superconducting Al wires.
AB  - Quantum phase slips have received much attention due to their relevance to
      superfluids in reduced dimensions and to models of cosmic string production in
      the early universe. Their establishment in one-dimensional superconductors has
      remained controversial. Here we study the nonlinear current-voltage
      characteristics and linear resistance in long superconducting Al wires with
      lateral dimensions approximately 5 nm. We find that, in a magnetic field and at
      temperatures well below the superconducting transition, the observed behaviors
      can be described by the nonclassical, macroscopic quantum tunneling of phase
      slips, and are inconsistent with the thermal activation of phase slips.

PMID- 16907398
TI  - Constituents of the quasiparticle spectrum along the nodal direction of high-Tc
      cuprates.
AB  - Applying the Kramers-Kronig consistent procedure, developed earlier, we
      investigate in detail the formation of the quasiparticle spectrum along the nodal
      direction of high-Tc cuprates. The heavily discussed "70 meV kink" on the
      renormalized dispersion exhibits a strong temperature and doping dependence when
      purified from structural effects such as bilayer splitting, diffraction replicas,
      etc. This dependence is well understood in terms of fermionic and bosonic
      constituents of the self-energy. The latter follows the evolution of the spin
      fluctuation spectrum, emerging below some doping dependent temperature and
      sharpening below Tc, and is mainly responsible for the formation of the kink in
      question.

PMID- 16907399
TI  - Magnetic excitations of stripes near a quantum critical point.
AB  - We calculate the dynamical spin structure factor of spin waves for weakly coupled
      stripes. At low energy, the spin-wave cone intensity is strongly peaked on the
      inner branches. As energy is increased, there is a saddlepoint followed by a
      square-shaped continuum rotated 45 degrees from the low energy peaks. This is
      reminiscent of recent high energy neutron scattering data on the cuprates. The
      similarity at high energy between this semiclassical treatment and quantum
      fluctuations in spin ladders may be attributed to the proximity of a quantum
      critical point with a small critical exponent eta.

PMID- 16907400
TI  - Flux cloning in Josephson transmission lines.
AB  - We describe a novel effect related to the controlled birth of a single Josephson
      vortex. In this phenomenon, the vortex is created in a Josephson transmission
      line at a T-shaped junction. The "baby" vortex arises at the moment when a
      "mother" vortex propagating in the adjacent transmission line passes the T-shaped
      junction. In order to give birth to a new vortex, the mother vortex must have
      enough kinetic energy. Its motion can also be supported by an externally applied
      driving current. We determine the critical velocity and the critical driving
      current for the creation of the baby vortices and briefly discuss the potential
      applications of the found effect.

PMID- 16907401
TI  - Competitive coexistence of superconductivity with antiferromagnetism in CeRhIn5.
AB  - We carried out ac magnetic susceptibility measurements under pressures P on the
      heavy fermion antiferromagnet CeRhIn5. We report bulk superconductivity (SC) at
      ambient pressure with a transition temperature Tc approximately or equal to 90
      mK. The degraded SC in a powdered or polished sample was restored by annealing,
      showing that the SC state is sensitive to inhomogeneity. In a coexistence region
      of the SC with antiferromagnetism (AF), we find that Tc(P)(n)TN(P)(1-n) = const
      where TN indicates a Neel temperature and n denotes a ratio of electronic
      specific heat coefficients below and above TN, indicating the competition of the
      SC and the AF for states at the Fermi surface.

PMID- 16907402
TI  - S-wave spin-triplet order in superconductors without inversion symmetry: Li2Pd3B
      and Li2Pt3B.
AB  - We investigate the order parameter of noncentrosymmetric superconductors Li2Pd3B
      and Li2Pt3B via the behavior of the penetration depth lambda(T). The low
      temperature penetration depth shows BCS-like behavior in Li2Pd3B, while in
      Li2Pt3B it follows a linear temperature dependence. We propose that broken
      inversion symmetry and the accompanying antisymmetric spin-orbit coupling, which
      admix spin-singlet and spin-triplet pairing, are responsible for this behavior.
      The triplet contribution is weak in Li2Pd3B, leading to a wholly open but
      anisotropic gap. The significantly larger spin-orbit coupling in Li2Pt3B allows
      the spin-triplet component to be larger in Li2Pt3B, producing line nodes in the
      energy gap as evidenced by the linear temperature dependence of lambda(T). The
      experimental data are in quantitative agreement with theory.

PMID- 16907403
TI  - Lee-Yang zeros of periodic and quasiperiodic anisotropic XY chains in a
      transverse field.
AB  - The partition function zeros of the anisotropic XY chain in a complex transverse
      field are studied analytically and numerically. It is found that the partition
      function zeros of the periodic and quasiperiodic quantum Ising chain lie on the
      circle at zero temperature and the radius equal to the values of the critical
      field. For the periodic and quasiperiodic anisotropic XY chains, the closed
      curves are split to two or three closed curves as the anisotropic parameter gamma
      decreases at a given ratio of two kinds of exchange interactions. For the
      isotropic XX case, the partition function zeros lie on the straight segments
      which are parallel to the real axis and the segments move towards the real axis
      as the temperature goes to zero.

PMID- 16907404
TI  - Remanent zero field spin splitting of self-assembled quantum dots in a
      paramagnetic host.
AB  - We report on the observation of a finite spin splitting at zero magnetic field in
      resonant tunneling experiments on CdSe self-assembled quantum dots in a
      (Zn,Be,Mn)Se barrier. This is remarkable since bulk II-VI dilute magnetic
      semiconductors are paramagnets. Our experiment may be viewed as tunneling through
      a single magnetic polaron, where the carriers contained inside the dot act to
      mediate an effective ferromagnetic interaction between Mn ions in their vicinity.
      The effect is observable up to relatively high temperatures, which we tentatively
      ascribe to a feedback mechanism with the electrical current, previously predicted
      theoretically.

PMID- 16907405
TI  - Direct experimental evidence for atomic tunneling of europium in crystalline
      Eu8Ga16Ge30.
AB  - Mossbauer-effect and microwave absorption experimental evidence unambiguously
      demonstrates the presence of slow, approximately 450 MHz, tunneling of magnetic
      europium between four equivalent sites in Eu8Ga16Ge30, a stoichiometric
      clathrate. Remarkably, six of the eight europium atoms, or 11% of the
      constituents in this solid, tunnel between these four sites separated by 0.55 A.
      The off centering of the atoms or ions in crystalline clathrates appears to be a
      promising route for producing Rabi oscillators in solid-state materials.

PMID- 16907406
TI  - Enhancement of single-molecule fluorescence using a gold nanoparticle as an
      optical nanoantenna.
AB  - We investigate the coupling of a single molecule to a single spherical gold
      nanoparticle acting as a nanoantenna. Using scanning probe technology, we
      position the particle in front of the molecule with nanometer accuracy and
      measure a strong enhancement of more than 20 times in the fluorescence intensity
      simultaneous to a 20-fold shortening of the excited state lifetime. Comparisons
      with three-dimensional calculations guide us to decipher the contributions of the
      excitation enhancement, spontaneous emission modification, and quenching.
      Furthermore, we provide direct evidence for the role of the particle plasmon
      resonance in the molecular excitation and emission processes.

PMID- 16907407
TI  - Phase diagram and electrical conductivity of high energy-density water from
      density functional theory.
AB  - The electrical conductivity and structure of water between 2000-70,000 K and 0.1
      3.7 g/cm3 is studied by finite temperature density functional theory (DFT).
      Proton conduction is investigated quantitatively by analyzing diffusion, the pair
      correlation function, and Wannier center locations, while the electronic
      conduction is calculated in the Kubo-Greenwood formalism. The conductivity
      formulation is valid across three phase transitions (molecular liquid, ionic
      liquid, superionic, electronic liquid). Above 100 GPa the superionic phase
      directly borders an electronically conducting fluid, not an insulating ionic
      fluid, as previously concluded. For simulations of high energy-density systems to
      be quantitative, we conclude that finite temperature DFT should be employed.

PMID- 16907408
TI  - Free cooling of the one-dimensional wet granular gas.
AB  - The free cooling behavior of a wet granular gas is studied in one dimension. We
      employ a particularly simple model system in which the interaction of wet grains
      is characterized by a fixed energy loss assigned to each collision. Macroscopic
      laws of energy dissipation and cluster formation are studied on the basis of
      numerical simulations and mean-field analytical calculations. We find a number of
      remarkable scaling properties which may shed light on earlier unexplained results
      for related systems.

PMID- 16907409
TI  - Song of the dunes as a self-synchronized instrument.
AB  - Since Marco Polo it has been known that some sand dunes have the peculiar ability
      to emit a loud sound with a well-defined frequency, sometimes for several
      minutes. The origin of this sustained sound has remained mysterious, partly
      because of its rarity in nature. It has been recognized that the sound is not due
      to the air flow around the dunes but to the motion of an avalanche, and not to an
      acoustic excitation of the grains but to their relative motion. By comparing
      singing dunes around the world and two controlled experiments, in the laboratory
      and the field, we prove that the frequency of the sound is the frequency of the
      relative motion of the sand grains. Sound is produced because moving grains
      synchronize their motions. The laboratory experiment shows that the dune is not
      needed for sound emission. A velocity threshold for sound emission is found in
      both experiments, and an interpretation is proposed.

PMID- 16907410
TI  - Dynamics and morphology of microvilli driven by actin polymerization.
AB  - Many different cell types have dynamic protrusions, called microvilli, on their
      surface. We model these structures as arising from the balance between the force
      of actin polymerization and the restoring force of the membrane. From this simple
      model we calculate the distribution function of microvilli heights for several
      cells. We further describe the phase diagram and the resulting morphology of the
      microvilli aggregates on the cell surface.

PMID- 16907411
TI  - Effect of confinement on the interaction between two like-charged rods.
AB  - Monte Carlo simulations were employed to study two charged rods confined between
      two unlike charged plates, all immersed in a model electrolyte. Recently, it was
      shown that two rods immersed in a multivalent counterion solution may show
      attraction [Phys. Rev. Lett. 78, 2477 (1997)10.1103/PhysRevLett.78.2477]. Here we
      show for a monovalent electrolyte that rod-rod attraction and repulsion can
      switch sign depending on confinement and ionic size. We also propose a simple
      self-assembling mechanism which may be helpful to understand the DNA-lipid
      bilayers complexation.

PMID- 16907412
TI  - Molecular sieving in periodic free-energy landscapes created by patterned
      nanofilter arrays.
AB  - We present an experimental study of Ogston-like sieving process of rodlike DNA in
      patterned periodic nanofluidic filter arrays. The electrophoretic motion of DNA
      through the array is described as a biased Brownian motion overcoming
      periodically modulated free-energy landscape. A kinetic model, constructed based
      on the equilibrium partitioning theory and the Kramers theory, explains the field
      dependent mobility well. We further show experimental evidence of the crossover
      from Ogston-like sieving to entropic trapping, depending on the ratio between
      nanofilter constriction size and DNA size.

PMID- 16907413
TI  - Light guiding in biological tissue due to scattering.
AB  - For a description of light propagation in biological tissue it is usually assumed
      that tissue is a random medium. We report a pronounced light guiding effect in
      cubes of human dentin that cannot be described by this standard model. Monte
      Carlo simulations which consider the microstructure of dentin are performed and
      successfully compared to experiments. Contrary to explanations so far, we show
      that light guiding is due to scattering by the tissue's microstructure.
      Exploiting this concept, light can be guided in arbitrary directions or locations
      without involving reflections or wave effects.

PMID- 16907414
TI  - Dissociative electron attachment to phosphoric acid esters: the direct mechanism
      for single strand breaks in DNA.
AB  - We use dibutyl phosphate to simulate the behavior of the phosphate group in DNA
      towards the attack of low energy electrons. We find that the compound undergoes
      effective dissociative electron attachment within a low energy resonant feature
      at 1 eV and a further resonance peaking at 8 eV. The dissociative electron
      attachment (DEA) reactions are associated with the direct cleavage of the C-O and
      the P-O bond but also the excision of the PO-, PO3-, H2PO3- units. For the
      phosphate group coupled in the DNA network these reactions represent single
      strand breaks. We hence propose that the most direct mechanism of single strand
      breaks occurring in DNA at subexcitation energies (< 4 eV) is due to DEA directly
      to the phosphate group.

PMID- 16907415
TI  - Switching mechanics with chemistry: a model for the bending stiffness of
      amphiphilic bilayers with interacting headgroups in crystalline order.
AB  - Bilayer structures in catanionic systems experimentally showed peculiar
      mechanical behavior. The observed increase in the bending stiffness is supposedly
      connected to additional hydrogen bonds forming between anionic headgroups. With a
      simple model, we can explain the extreme sensitivity of the bending stiffness of
      the membrane on the molar ratio of the charged molecules. This effect is further
      amplified by the sandwichlike structure of the membrane, where the apolar core
      separating the headgroups acts via a kind of lever-arm principle. As a
      consequence of these combined effects, the model membrane changes from a soft
      behavior with bending rigidities on the order of 10k(B)T to an extremely stiff
      membrane with a bending stiffness more than 2 orders of magnitude larger where
      most of this change occurs within a molar ratio interval smaller than 0.1.

PMID- 16907416
TI  - Single polymer molecules in a protein nanopore in the limit of a strong polymer
      pore attraction.
AB  - The capture and release of single poly(ethylene glycol) molecules by the alpha
      Hemolysin pore are observed as time-resolved reversible steps in ion conductance.
      The capture on rate, inferred from the step frequency, decreases monotonically
      with polymer size. However, the polymer residence time shows a crossover
      behavior, first increasing and then decreasing with molecular weight. Our
      interpretation is that, in the case of polymers which are too large to be
      accommodated within the pore, the out-of-the-pore part of the molecule pulls on
      the trapped part, thus acting as an entropic spring.

PMID- 16907417
TI  - Prediction of an autocatalytic replication mechanism for micelle formation.
AB  - We report molecular simulations suggesting that the kinetics of surfactant
      micelle formation can be sped up significantly by a replication mechanism, in
      which growing micelles become unstable and split into two similar sized micelles.
      We argue that for certain surfactants types around the critical micelle
      concentration, such a mechanism becomes more dominant than the commonly accepted
      nucleation pathway.

PMID- 16907418
TI  - Contact instability in adhesion and debonding of thin elastic films.
AB  - Based on experiments and 3D simulations, we show that a soft elastic film during
      adhesion and debonding from a rigid flat surface undergoes morphological
      transitions to pillars, labyrinths, and cavities, all of which have the same
      lateral pattern length scale, lambda close to lambda/H approximately 3 for thick
      films, H > 1 microm . The linear stability analysis and experiments show a new
      thin film regime where lambda/H approximately equal to 3 + 2pi(lambda/3 muH)1/4
      (gamma is surface tension, mu is shear modulus) because of a significant surface
      energy penalty (for example, lambda/H approximately equal to 6 for H = 200 nm; mu
      = 1 MPa).

PMID- 16907419
TI  - Wetting and contact lines of micrometer-sized ellipsoids.
AB  - We experimentally and theoretically investigate the shapes of contact lines on
      the surfaces of micrometer-sized polystyrene ellipsoids at the water-air
      interface. By combining interferometry and optical trapping, we directly observe
      quadrupolar symmetry of the interface deformations around such particles. We then
      develop numerical solutions of the partial wetting problem for ellipsoids, and
      use these solutions to deduce the shapes of the corresponding contact lines and
      the values of the contact angles, theta(c)(k), as a function of the ellipsoid
      aspect ratio k. Surprisingly, theta(c) is found to decrease for increasing k
      suggesting that ellipsoid microscopic surface properties depend on ellipsoid
      aspect ratio.

PMID- 16907420
TI  - Spontaneous spin textures in dipolar spinor condensates.
AB  - We have mapped out a detailed phase diagram that shows the ground state structure
      of a spin-1 condensate with magnetic dipole-dipole interactions. We show that the
      interplay between the dipolar and the spin-exchange interactions induces a rich
      variety of quantum phases that exhibit spontaneous magnetic ordering in the form
      of intricate spin textures.

PMID- 16907421
TI  - Induced P-wave superfluidity in asymmetric fermi gases.
AB  - We show that two new intraspecies P-wave superfluid phases appear in two
      component asymmetric Fermi systems with short-range S-wave interactions. In the
      BEC limit, phonons of the molecular BEC induce P-wave superfluidity in the excess
      fermions. In the BCS limit, density fluctuations induce P-wave superfluidity in
      both the majority and the minority species. These phases may be realized in
      experiments with spin-polarized Fermi gases.

PMID- 16907422
TI  - Experimental entangled entanglement.
AB  - All previous tests of local realism have studied correlations between single
      particle measurements. In the present experiment, we have performed a Bell
      experiment on three particles in which one of the measurements corresponds to a
      projection onto a maximally entangled state. We show theoretically and
      experimentally that correlations between these entangled measurements and single
      particle measurements are too strong for any local-realistic theory and are
      experimentally exploited to violate a Clauser-Horne-Shimony-Holt-Bell inequality
      by more than 5 standard deviations. We refer to this possibility as "entangled
      entanglement."

PMID- 16907423
TI  - Universally programmable quantum cellular automaton.
AB  - We discuss the role of classical control in the context of reversible quantum
      cellular automata. Employing the structure theorem for quantum cellular automata,
      we give a general construction scheme to turn an arbitrary cellular automaton
      with external classical control into an autonomous one, thereby proving the
      computational equivalence of these two models. We use this technique to construct
      a universally programmable cellular automaton on a one-dimensional lattice with
      single cell dimension 12.

PMID- 16907424
TI  - Identity of distributions of direct uphill and downhill translocation times for
      particles traversing membrane channels.
AB  - We study the distribution of direct translocation times for particles passing
      through membrane channels connecting two reservoirs. The direct translocation
      time is a conditional first-passage time defined as the residence time of the
      particle in the channel while passing to the other side of the membrane directly,
      i.e., without returning to the reservoir from which it entered. We show that the
      distributions of direct translocation times are identical for translocation in
      both directions, independent of any asymmetry in the potential across the channel
      and, hence, the translocation probabilities.

PMID- 16907425
TI  - Coherent control of harmonic generation in superlattices: single-mode response.
AB  - We study the harmonic generation spectrum in a semiconductor superlattice (a
      quantum-dot array) at slow relaxation. The effect of a single-mode response in an
      alternating rectangular (meander) electric field is demonstrated: For certain
      values of field parameters, the extremely wide discrete output spectrum with
      slowly decaying tails (multiharmonic generation) shrinks to one single harmonic
      (single-harmonic generation). Similarly, the effect is manifested in the
      transient continuous spectrum by diminishing the divergencies (peaks) at all odd
      harmonics but one. Substantial control over the spectrum is demonstrated.

PMID- 16907426
TI  - Single-atom optical clock with high accuracy.
AB  - For the past 50 years, atomic standards based on the frequency of the cesium
      ground-state hyperfine transition have been the most accurate time pieces in the
      world. We now report a comparison between the cesium fountain standard NIST-F1,
      which has been evaluated with an inaccuracy of about 4 x 10(-16), and an optical
      frequency standard based on an ultraviolet transition in a single, laser-cooled
      mercury ion for which the fractional systematic frequency uncertainty was below
      7.2 x 10(-17). The absolute frequency of the transition was measured versus
      cesium to be 1,064,721,609,899,144.94 (97) Hz, with a statistically limited total
      fractional uncertainty of 9.1 x 10(-16) the most accurate absolute measurement of
      an optical frequency to date.

PMID- 16907427
TI  - Calculation of the first nonlinear contribution to the general-relativistic spin
      spin interaction for binary systems.
AB  - We use recently developed effective field theory techniques to calculate the
      third order post-Newtonian correction to the spin-spin potential between two
      spinning objects. This correction represents the first contribution to the spin
      spin interaction due to the nonlinear nature of general relativity and will play
      an important role in forthcoming gravity wave experiments.

PMID- 16907428
TI  - New cosmic microwave background constraint to primordial gravitational waves.
AB  - Primordial gravitational waves (GWs) with frequencies > or approximately equal to
      10(-15) Hz contribute to the radiation density of the Universe at the time of
      decoupling of the cosmic microwave background (CMB). This affects the CMB and
      matter power spectra in a manner identical to massless neutrinos, unless the
      initial density perturbation for the GWs is nonadiabatic, as may occur if such
      GWs are produced during inflation or some post-inflation phase transition. In
      either case, current observations provide a constraint to the GW amplitude that
      competes with that from big-bang nucleosynthesis (BBN), although it extends to
      much lower frequencies (approximately 10(-15) Hz rather than the approximately
      10(-10) Hz from BBN): at 95% confidence level, omega(gw)h(2) <or approximately =
      8.4 x 10(-6) for homogeneous (i.e., nonadiabatic) initial conditions. Future CMB
      experiments, like Planck and CMBPol, should allow sensitivities to omega(gw)h(2)
      <or approximately = 1.4 x 10(-6) and omega(gw)h(2) < or approximately 5 x 10(-7),
      respectively.

PMID- 16907429
TI  - Producing a scale-invariant spectrum of perturbations in a Hagedorn phase of
      string cosmology.
AB  - We study the generation of cosmological perturbations during the Hagedorn phase
      of string gas cosmology. Using tools of string thermodynamics we provide
      indications that it may be possible to obtain a nearly scale-invariant spectrum
      of cosmological fluctuations on scales which are of cosmological interest today.
      In our cosmological scenario, the early Hagedorn phase of string gas cosmology
      goes over smoothly into the radiation-dominated phase of standard cosmology,
      without having a period of cosmological inflation.

PMID- 16907430
TI  - Very special relativity.
AB  - By very special relativity (VSR) we mean descriptions of nature whose space-time
      symmetries are certain proper subgroups of the Poincare group. These subgroups
      contain space-time translations together with at least a two-parameter subgroup
      of the Lorentz group isomorphic to that generated by K(x) + J(y) and K(y)- J(x).
      We find that VSR implies special relativity (SR) in the context of local quantum
      field theory or of conservation. Absent both of these added hypotheses, VSR
      provides a simulacrum of SR for which most of the consequences of Lorentz
      invariance remain wholly or essentially intact, and for which many sensitive
      searches for departures from Lorentz invariance must fail. Several feasible
      experiments are discussed for which Lorentz-violating effects in VSR may be
      detectable.

PMID- 16907431
TI  - Collisions of strings with Y junctions.
AB  - We study the dynamics of Nambu-Goto strings with junctions at which three strings
      meet. In particular, we exhibit one simple exact solution and examine the process
      of intercommuting of two straight strings in which they exchange partners but
      become joined by a third string. We show that there are important kinematical
      constraints on this process. The exchange cannot occur if the strings meet with
      very large relative velocity. This may have important implications for the
      evolution of cosmic superstring networks and non-Abelian string networks.

PMID- 16907432
TI  - New CP-violation and preferred-frame tests with polarized electrons.
AB  - We used a torsion pendulum containing approximately 9 x 10(22) polarized
      electrons to search for CP-violating interactions between the pendulum's
      electrons and unpolarized matter in the laboratory's surroundings or the Sun, and
      to test for preferred-frame effects that would precess the electrons about a
      direction fixed in inertial space. We find, /g(P)(e)g(S)(N)//(Planck's constant x
      c) < 1.7 x 10(-36), and /g(A)(e)g(V)(N)//(Planck's constant x c) < 4.8 x 10(-56)
      for lambda > 1 AU. Our preferred-frame constraints, interpreted in the Kostelecky
      framework, set an upper limit on the parameter /b(e)/ <or= 5.0 x 10(-21) eV that
      should be compared to the benchmark value m(e)(2)/M(Planck)= 2 x 10(-17) eV.

PMID- 16907433
TI  - Probing a very narrow Z' boson with CDF and D0 Data.
AB  - The CDF and D0 data of nearly 475 pb(-1) in the dilepton channel is used to probe
      a recent class of models, Stueckelberg extensions of the standard model (StSM),
      which predict a Z' boson whose mass is of topological origin with a very narrow
      decay width. A Drell-Yan analysis for dilepton production via this Z' shows that
      the current data put constraints on the parameter space of the StSM. With a total
      integrated luminosity of 8 fb(-1), the very narrow can be discovered up to a mass
      of about 600 GeV. The StSM Z' will be very distinct since it can occur in the
      region where a Randall-Sundrum graviton is excluded.

PMID- 16907435
TI  - Upper bounds on supersymmetric contributions to b-->s transitions from Bs-Bs
      mixing.
AB  - We study the constraints on supersymmetric contributions to b-->s transitions
      from the recent allowed range and measurement of B(s)-B(s) mixing obtained by the
      D0 and Collider Detector at Fermilab collaborations at the Tevatron. We compute
      the upper bounds on the relevant off-diagonal squark mass terms and compare them
      with the bounds coming from delta F= 1 decays. We find that the constraints on
      chirality-flipping mass insertions are unaffected. Conversely, the measurement of
      B(s)-B(s) mixing is effective in constraining chirality-conserving mass
      insertions, and it has striking effects in the case in which left- and right
      handed insertions have similar size. Finally, we discuss the phase of the B(s)
      B(s) mixing amplitude in the presence of supersymmetric contributions.

PMID- 16907436
TI  - Strange electric form factor of the proton.
AB  - By combining the constraints of charge symmetry with new chiral extrapolation
      techniques and recent low-mass quenched lattice QCD simulations of the individual
      quark contributions to the electric charge radii of the baryon octet, we obtain
      an accurate determination of the strange electric charge radius of the proton.
      While this analysis provides a value for G(E)(s)(Q(2) = 0.1 GeV(2)) in agreement
      with the best current data, the theoretical error is comparable with that
      expected from future HAPPEX results from JLab. Together with the earlier
      determination of G(M)(s), this result considerably constrains the role of hidden
      flavor in the structure of the nucleon.

PMID- 16907437
TI  - Photoexcitation of K-shell and L-shell hollow beryllium.
AB  - We have observed K-shell and L-shell hollow beryllium atoms (2s(2)2p3s and
      1s3s(2)3p) created by photoexcitation using synchrotron radiation. Resonance
      shapes were fitted to the Fano profile and the parameters were deduced. A Dirac
      Fock calculation was performed to identify the configuration of the peaks and to
      predict other hollow atomic peaks. The results of the calculation were in good
      agreement with the experimental data. The comparison of the transition strength
      has revealed that the three-electron photoexcitation to the 1s3s(2)3p
      configuration is stronger than the two-electron photoexcitation to the 2s(2)2p3s
      configuration. This is attributed to the large overlap between the 2s orbital of
      the ground state (1s(2)2s(2)) with the orbital of the L-shell hollow state
      (1s3s(2)3p).

PMID- 16907438
TI  - Resonator-aided single-atom detection on a microfabricated chip.
AB  - We use an optical cavity to detect single atoms magnetically trapped on an atom
      chip. We implement the detection using both fluorescence into the cavity and atom
      induced reduction in cavity transmission. In fluorescence, we register 2.0(2)
      photon counts per atom, which allows us to detect single atoms with 75%
      efficiency in 250 micros. In absorption, we measure transmission attenuation of
      3.3(3)% per atom, which allows us to count small numbers of atoms with a
      resolution of about 1 atom.

PMID- 16907439
TI  - Properties of pseudopotentials for higher partial waves.
AB  - Contact psuedopotentials for relative angular momentum greater than zero are of
      interest for the study of cold atomic gases. For bosons, it is known that when
      the s-wave scattering length becomes infinite, an infinite number of three-body
      bound states, called Efimov states, are predicted by such potentials. Realistic
      potentials also exhibit the such states, thus a study of the Efimov effect for
      contact psuedopotentials for higher partial waves and fermions is important for
      the study of cold atoms. In this Letter we analyze three-body states of three
      particles interacting via psuedopotentials for higher partial waves and show that
      there is an Efimov effect for three fermions interacting via p-wave
      psuedopotentials.

PMID- 16907440
TI  - Interferences in parametric interactions driven by quantized fields.
AB  - We report interferences in the quantum fluctuations of the output of a parametric
      amplifier when the cavity is driven by a quantized field at the signal frequency.
      The interferences depend on the phase fluctuations of the input quantized field
      and result in splitting of the spectrum of the output, and thus the recent
      observation [H. Ma, Phys. Rev. Lett. 95, 233601
      (2005)10.1103/PhysRevLett.95.233601] of interferences in the classical domain
      have a very interesting counterpart in the quantum domain. The interferences can
      be manipulated, for example, by changing the amount of squeezing in the input
      field.

PMID- 16907441
TI  - Realization of four-level qudits using biphotons.
AB  - The novel experimental realization of four-level optical quantum systems
      (ququarts) is presented. We exploit the polarization properties of the frequency
      nondegenerate biphoton field to obtain such systems. A simple method that does
      not rely on am interferometer is used to generate and measure the sequence of
      states that can be used in quantum key distribution protocol.

PMID- 16907442
TI  - Low-light-level optical interactions with rubidium vapor in a photonic band-gap
      fiber.
AB  - We show that rubidium vapor can be produced within the core of a photonic band
      gap fiber yielding an optical depth in excess of 2,000. Our technique for
      producing the vapor is based on coating the inner walls of the fiber core with
      organosilane and using light-induced atomic desorption to release Rb atoms into
      the core. As an initial demonstration of the potential of this system for
      supporting ultralow-level nonlinear optical interactions, we perform
      electromagnetically induced transparency with control-field powers in the
      nanowatt regime, which represents more than a 1,000-fold reduction from the power
      required for bulk, focused geometries.

PMID- 16907443
TI  - Demonstration of temporal distinguishability in a four-photon state and a six
      photon state.
AB  - An experiment is performed to demonstrate the temporal distinguishability of a
      four-photon state and a six-photon state, both from parametric down-conversion.
      The experiment is based on a multiphoton interference scheme in a recently
      discovered projection measurement of a maximally entangled N-photon state. By
      measuring the visibility of the interference dip, we can distinguish the various
      scenarios in the temporal distribution of the pairs and, thus, quantitatively
      determine the degree of temporal distinguishability of a multiphoton state.

PMID- 16907444
TI  - Spin squeezing and light entanglement in coherent population trapping.
AB  - We show that strong squeezing and entanglement can be generated at the output of
      a cavity containing atoms interacting with two fields in a coherent population
      trapping situation, on account of a nonlinear Faraday effect experienced by the
      fields close to a dark-state resonance in a cavity. Moreover, the cavity provides
      a feedback mechanism allowing to reduce the quantum fluctuations of the ground
      state spin, resulting in strong steady state spin squeezing.

PMID- 16907445
TI  - Many-body quantum dynamics of polarization squeezing in optical fibers.
AB  - We report new experiments that test quantum dynamical predictions of polarization
      squeezing for ultrashort photonic pulses in a birefringent fiber, including all
      relevant dissipative effects. This exponentially complex many-body problem is
      solved by means of a stochastic phase-space method. The squeezing is calculated
      and compared to experimental data, resulting in excellent quantitative agreement.
      From the simulations, we identify the physical limits to quantum noise reduction
      in optical fibers. The research represents a significant experimental test of
      first-principles time-domain quantum dynamics in a one-dimensional interacting
      Bose gas coupled to dissipative reservoirs.

PMID- 16907446
TI  - Direct interferometric measurement of the atomic dipole phase in high-order
      harmonic generation.
AB  - We report the first direct measurements of the atomic dipole phase in the process
      of high-order harmonic generation. Differently from previously reported studies
      based on frequency chirp measurements, we use extreme ultraviolet interferometry
      as the most natural and direct way to measure phase shifts. Our approach has the
      important advantage of allowing us to investigate the effects associated to both
      the main quantum paths involved in the emission of a particular harmonic, thus
      offering a particularly clear and simple picture of the underlying electronic
      dynamics.

PMID- 16907447
TI  - Quantum temporal correlations and entanglement via adiabatic control of vector
      solitons.
AB  - It is shown that optical pulses with an average position accuracy beyond the
      standard quantum limit can be produced by adiabatically expanding an optical
      vector soliton followed by classical dispersion management. The proposed scheme
      is also capable of entangling positions of optical pulses and can potentially be
      used for general continuous-variable quantum-information processing.

PMID- 16907448
TI  - Optomechanical wavelength and energy conversion in high- double-layer cavities of
      photonic crystal slabs.
AB  - We demonstrate that ultrasmall double-layer photonic-crystal-slab cavities
      exhibit a very high-Q value for a wide range of the layer spacing, which enables
      us to realize unique optomechanical coupling. By mechanically varying the
      separation, we can achieve extraordinarily large wavelength conversion. In
      addition, the light stored in the cavity can generate a large radiation force. We
      show that this system exhibits extremely high energy conversion efficiency
      between optical and mechanical energy, leading to a novel approach for the
      optomechanical control of light and matter.

PMID- 16907449
TI  - Tunable ultrashort laser pulses generated through filamentation in gases.
AB  - Tunable and stable ultrashort laser pulses in the visible spectrum are generated
      with high efficiency by four-wave mixing process during the filamentation of near
      infrared and infrared laser pulses in gases. It is shown that these tunable
      ultrashort pulses have a very low energy fluctuation and an excellent mode
      quality due to the processes of intensity clamping and self-filtering in the
      filament.

PMID- 16907434
TI  - Direct limits on the oscillation frequency.
AB  - We report results of a study of the B(s)(0) oscillation frequency using a large
      sample of B(s)(0) semileptonic decays corresponding to approximately 1 fb(-1) of
      integrated luminosity collected by the D0 experiment at the Fermilab Tevatron
      Collider in 2002-2006. The amplitude method gives a lower limit on the B(s)(0)
      oscillation frequency at 14.8 ps(-1) at the 95% C.L. At delta m(s) = 19 ps(-1),
      the amplitude deviates from the hypothesis A= 0(1) by 2.5 (1.6) standard
      deviations, corresponding to a two-sided C.L. of 1% (10%). A likelihood scan over
      the oscillation frequency, delta m(s), gives a most probable value of 19 ps(-1)
      and a range of 17 < delta m(s) < 21 ps(-1)at the 90% C.L., assuming Gaussian
      uncertainties. This is the first direct two-sided bound measured by a single
      experiment. If delta m(s) lies above 22 ps(-1), then the probability that it
      would produce a likelihood minimum similar to the one observed in the interval 16
      22 ps(-1) is (5.0 +/- 0.3)%.

PMID- 16907450
TI  - Chaos without nonlinear dynamics.
AB  - A linear, second-order filter driven by randomly polarized pulses is shown to
      generate a waveform that is chaotic under time reversal. That is, the filter
      output exhibits determinism and a positive Lyapunov exponent when viewed backward
      in time. The filter is demonstrated experimentally using a passive electronic
      circuit, and the resulting waveform exhibits a Lorenz-like butterfly structure.
      This phenomenon suggests that chaos may be connected to physical theories whose
      underlying framework is not that of a traditional deterministic nonlinear
      dynamical system.

PMID- 16907451
TI  - Molecular understanding of osmosis in semipermeable membranes.
AB  - We investigate single-file osmosis of water through a semipermeable membrane with
      an uncharged, a positively and a negatively charged nanopore. Molecular dynamics
      simulations indicate that the osmotic flux through a negatively charged pore (J_)
      is higher compared to the osmotic flux in a positively charged pore (J+) followed
      by the osmotic flux in the uncharged pore (J(0)), i.e., J_ > J+ > J(0). The
      molecular mechanisms governing osmosis, steady state osmosis, and the observed
      osmotic flux dependence on the nanopore charge are explained by computing all the
      molecular interactions involved and identifying the molecular interactions that
      play an important role during and after osmosis. This study helps in a
      fundamental understanding of osmosis and in the design of advanced nanoporous
      membranes for various applications of osmosis.

PMID- 16907452
TI  - Nonlinear triad interactions and the mechanism of spreading in drift-wave
      turbulence.
AB  - We present the results of a derivation of the fluctuation energy transport matrix
      for the two-field Hasegawa-Wakatani model of drift wave turbulence. The energy
      transport matrix is derived from a two-scale direct interaction approximation
      assuming weak turbulence. We examine different classes of triad interactions and
      show that radially extended eddies, as occurs in penetrative convection, are the
      most effective in turbulence spreading. We show that in the near-adiabatic limit
      internal energy spreads faster than the kinetic energy. Previous theories of
      spreading results are discussed in the context of weak turbulence theory.

PMID- 16907453
TI  - Flowing crystals: nonequilibrium structure of foam.
AB  - Bubbles pushed through a quasi-two-dimensional channel self-organize into a
      variety of periodic lattices. The structures of these lattices correspond to
      local minima of the interfacial energy. The "flowing crystals" are long-lived
      metastable states, a small subset of possible local minima of confined quasi-two
      dimensional foams [P. Garstecki and G. M. Whitesides, Phys. Rev. E 73, 031603
      (2006)10.1103/PhysRevE.73.031603]. Experimental results suggest that the choice
      of the structures that we observe is dictated by the dynamic stability of the
      cyclic processes of their formation. Thus, the dynamic system that we report
      provides a unique example of nonequilibrium self-organization that results in
      structures that correspond to local minima of the relevant energy functional.

PMID- 16907454
TI  - Interlayer forces and ultralow sliding friction in multiwalled carbon nanotubes.
AB  - We describe interlayer force measurements during prolonged, cyclic telescoping
      motion of a multiwalled carbon nanotube. The force acting between the core and
      the outer casing is modulated by the presence of stable defects and generally
      exhibits ultralow friction, below the measurement limit of 1.4 x 10(-15) N/atom
      and total dissipation per cycle lower than 0.4 meV/atom. Defects intentionally
      introduced in the form of dangling bonds lead to temporary mechanical
      dissipation, but the innate ability of nanotubes to self heal rapidly optimizes
      the atomic structure and restores smooth motion.

PMID- 16907455
TI  - Dissociation of liquid silica at high pressures and temperatures.
AB  - Liquid silica at high pressure and temperature is shown to undergo significant
      structural modifications and profound changes in its electronic properties.
      Temperature measurements on shock waves in silica at 70-1,000 GPa indicate that
      the specific heat of liquid rises SiO(2) well above the Dulong-Petit limit,
      exhibiting a broad peak with temperature that is attributable to the growing
      structural disorder caused by bond breaking in the melt. The simultaneous sharp
      rise in optical reflectivity of liquid SiO(2) indicates that such dissociation
      causes the electrical and therefore thermal conductivities of silica to attain
      metalliclike values of 1-5 x 10(5) S/m and 24-600 W/m x K, respectively.

PMID- 16907456
TI  - Weak turbulence for a vibrating plate: can one hear a Kolmogorov spectrum?
AB  - We study the long-time evolution of waves of a thin elastic plate in the limit of
      small deformation so that modes of oscillations interact weakly. According to the
      theory of weak turbulence (successfully applied in the past to plasma, optics,
      and hydrodynamic waves), this nonlinear wave system evolves at long times with a
      slow transfer of energy from one mode to another. We derive a kinetic equation
      for the spectral transfer in terms of the second order moment. We show that such
      a theory describes the approach to an equilibrium wave spectrum and represents
      also an energy cascade, often called the Kolmogorov-Zakharov spectrum. We perform
      numerical simulations that confirm this scenario.

PMID- 16907457
TI  - Observation of a pressure-induced first-order polyamorphic transition in a
      chalcogenide glass at ambient temperature.
AB  - An apparently first-order polyamorphic transition has been observed with
      increasing pressure at ambient temperature in a molecular glass of composition
      Ge(2.5)As(51.25)S(46.25) Raman spectroscopic measurements on pressure-quenched
      samples and in situ x-ray diffraction measurements indicate that this transition
      corresponds to a collapse of the ambient-pressure molecular phase to a high
      pressure network phase. The high-pressure phase first appears at a pressure of
      approximately 8-9 GPa and the transformation becomes complete at approximately 14
      15 GPa. Calorimetric measurements indicate that the low- and high-pressure phases
      are thermodynamically distinct and that they coexist in the transition range.

PMID- 16907458
TI  - q-Breathers in finite two- and three-dimensional nonlinear acoustic lattices.
AB  - In their celebrated experiment, Fermi, Pasta, and Ulam (FPU) [Los Alamos Report
      No. LA-1940, 1955] observed that in simple one-dimensional nonlinear atomic
      chains the energy must not always be equally shared among the modes. Recently, it
      was shown that exact and stable time-periodic orbits, coined q-breathers (QBs),
      localize the mode energy in normal mode space in an exponential way, and account
      for many aspects of the FPU problem. Here we take the problem into more
      physically important cases of two- and three-dimensional acoustic lattices to
      find existence and principally different features of QBs. By use of perturbation
      theory and numerical calculations we obtain that the localization and stability
      of QBs are enhanced with increasing system size in higher lattice dimensions
      opposite to their one-dimensional analogues.

PMID- 16907459
TI  - Fresnel coherent diffractive imaging.
AB  - We present an x-ray coherent diffractive imaging experiment utilizing a nonplanar
      incident wave and demonstrate success by reconstructing a nonperiodic gold sample
      at 24 nm resolution. Favorable effects of the curved beam illumination are
      identified.

PMID- 16907460
TI  - Phase separation in a compressible 2D Ising model.
AB  - We perform a high precision Monte Carlo study of asymptotic domain growth in a
      compressible two-dimensional spin-exchange Ising model with continuous particle
      positions and zero total magnetization, and we investigate the effects of
      compressibility and lattice mismatch on the late-time domain growth law, R(t) = A
      + Bt(n). For mismatched systems, we measure significant deviations from the
      theoretically expected n = 1/3 late-time growth (n = 0.224 +/- 0.004), and for a
      compressible model with no mismatch, we measure only a slight deviation from n =
      1/3. These results strongly suggest that the current understanding of the classes
      of domain growth is incomplete.

PMID- 16907461
TI  - Critical dynamics in a binary fluid: simulations and finite-size scaling.
AB  - We report comprehensive simulations of the critical dynamics of a symmetric
      binary Lennard-Jones mixture near its consolute point. The self-diffusion
      coefficient exhibits no detectable anomaly. The data for the shear viscosity and
      the mutual-diffusion coefficient are fully consistent with the asymptotic power
      laws and amplitudes predicted by renormalization-group and mode-coupling theories
      provided finite-size effects and the background contribution to the relevant
      Onsager coefficient are suitably accounted for. This resolves a controversy
      raised by recent molecular simulations.

PMID- 16907462
TI  - Nature of asymmetry in fluid criticality.
AB  - By combining accurate liquid-vapor coexistence and heat-capacity data, we have
      unambiguously separated two nonanalytical contributions of liquid-gas asymmetry
      in fluid criticality and showed the validity of "complete scaling" [Fisher, Phys.
      Rev. Lett. 85, 696 (2000)10.1103/PhysRevLett.85.696; Phys. Rev. E 67, 061506
      (2003)10.1103/PhysRevE.67.061506]. We have also developed a method to obtain two
      scaling-field coefficients, responsible for the two sources of the asymmetry,
      from mean-field equations of state. Since the asymmetry effects are completely
      determined by Ising critical exponents, there is no practical need for a special
      renormalization-group theoretical treatment of asymmetric fluid criticality.

PMID- 16907463
TI  - Oxidation catalysis by oxide-supported Au nanostructures: the role of supports
      and the effect of external conditions.
AB  - Oxide-supported Au nanostructures are promising low-temperature oxidation
      catalysts. It is generally observed that Au supported on reducible oxides is more
      active than Au supported on irreducible oxides. Recent studies also suggest that
      cationic Au(delta+) is responsible for the unique Au/oxide catalytic activity,
      contrary to the conventional perception that oxide supports donate electronic
      charge to Au. We have utilized density functional calculations and ab initio
      thermodynamic studies to investigate the oxidation state of Au nanostructures
      deposited on reducible and irreducible supports. We find that there are
      fundamental differences in the electronic structure of Au deposited on the
      different oxides. We propose a simple model, grounded in the first principles
      calculations, which can explain the oxide-specific catalytic activity of Au
      nanostructures and which can account for the presence and the role of cationic
      Au(delta+).

PMID- 16907464
TI  - Half-metallic diluted antiferromagnetic semiconductors.
AB  - The possibility of half-metallic antiferromagnetism, a special case of
      ferrimagnetism with a compensated magnetization, in the diluted magnetic
      semiconductors is highlighted on the basis of the first-principles electronic
      structure calculation. As typical examples, the electrical and magnetic
      properties of II-VI compound semiconductors doped with 3d transition metal ion
      pairs--(V, Co) and (Fe, Cr)--are discussed.

PMID- 16907465
TI  - Pressure-induced transition in magnetoresistance of single-walled carbon
      nanotubes.
AB  - We applied hydrostatic pressure (up to 10 GPa) to single-walled carbon nanotube
      bundles at low temperature (down to 2 K) to measure their magnetoresistance (MR)
      in a field up to 12 T. We found a pressure-induced transition in MR from positive
      to negative in the high-field regime. The onset of the transition occurs at
      approximately 1.5 GPa, which correlates closely with the tube shape transitions.
      The characteristics of the high-pressure MR are consistent with a model of
      pressure-induced two-dimensional weak localization.

PMID- 16907466
TI  - Zeeman splitting in ballistic hole quantum wires.
AB  - We have studied the Zeeman splitting in ballistic hole quantum wires formed in a
      (311)A quantum well by surface gate confinement. Transport measurements clearly
      show lifting of the spin degeneracy and crossings of the subbands when an in
      plane magnetic field B is applied parallel to the wire. When B is oriented
      perpendicular to the wire, no spin splitting is discernible up to B = 8.8 T. The
      observed large Zeeman splitting anisotropy in our hole quantum wires demonstrates
      the importance of quantum confinement for spin splitting in nanostructures with
      strong spin-orbit coupling.

PMID- 16907467
TI  - Thermal collapse of spin polarization in half-metallic ferromagnets.
AB  - We propose two novel approaches to study the temperature dependence of the
      magnetization and the spin polarization at the Fermi level in magnetic compounds,
      and apply them to half-metallic ferromagnets. We reveal a new mechanism, where
      the hybridization of states forming the half-metallic gap depends on thermal spin
      fluctuations and the polarization can drop abruptly at temperatures much lower
      than the Curie point. We verify this for NiMnSb by ab initio calculations. The
      thermal properties are studied by mapping ab initio results to an extended
      Heisenberg model which includes longitudinal fluctuations and is solved by a
      Monte Carlo method.

PMID- 16907468
TI  - Quantum transport of slow charge carriers in quasicrystals and correlated
      systems.
AB  - We show that the semiclassical model of conduction breaks down if the mean free
      path of charge carriers is smaller than a typical extension of their wave
      function. This situation is realized for sufficiently slow charge carriers and
      leads to a transition from a metalliclike to an insulatinglike regime when
      scattering by defects increases. This explains the unconventional conduction
      properties of quasicrystals and related alloys. The conduction properties of some
      heavy fermions or polaronic systems, where charge carriers are also slow, present
      a deep analogy.

PMID- 16907469
TI  - Spin injection and detection in silicon.
AB  - Spin injection and detection in silicon is a difficult problem, in part because
      the weak spin-orbit coupling and indirect gap preclude using standard optical
      techniques. Two ways to overcome this difficulty are proposed, both based on spin
      polarized transport across a heterojunction. Using a realistic transport model
      incorporating the relevant spin dynamics of both electrons and holes, it is
      argued that symmetry properties of the charge current can be exploited to detect
      electrical spin injection in silicon using currently available techniques.

PMID- 16907470
TI  - Berry-phase effect in anomalous thermoelectric transport.
AB  - We develop a theory of the Berry-phase effect in anomalous transport in
      ferromagnets driven by statistical forces such as the gradient of temperature or
      chemical potential. Here a charge Hall current arises from the Berry-phase
      correction to the orbital magnetization rather than from the anomalous velocity,
      which does not exist in the absence of a mechanical force. A finite-temperature
      formula for the orbital magnetization is derived, which enables us to provide an
      explicit expression for the off-diagonal thermoelectric conductivity, to
      establish the Mott relation between the anomalous Nernst and Hall effects, and to
      reaffirm the Onsager relations between reciprocal thermoelectric conductivities.
      A first-principles evaluation of our expression is carried out for the material
      CuCr(2)Se(4-x)Br(x), obtaining quantitative agreement with a recent experiment.

PMID- 16907471
TI  - Transition from direct tunneling to field emission in metal-molecule-metal
      junctions.
AB  - Current-voltage measurements of metal-molecule-metal junctions formed from pi
      conjugated thiols exhibit an inflection point on a plot of ln(I/V(2)) vs 1/V,
      consistent with a change in transport mechanism from direct tunneling to field
      emission. The transition voltage was found to scale linearly with the offset in
      energy between the Au Fermi level and the highest occupied molecular orbital as
      determined by ultraviolet photoelectron spectroscopy. Asymmetric voltage drops at
      the two metal-molecule interfaces cause the transition voltage to be dependent on
      bias polarity.

PMID- 16907472
TI  - Kohn-Sham exchange potential for a metallic surface.
AB  - The behavior of the surface barrier that forms at the metal-vacuum interface is
      important for several fields of surface science. Within the density functional
      theory framework, this surface barrier has two nontrivial components: exchange
      and correlation. Exact results are provided for the exchange component, for a
      jellium metal-vacuum interface, in a slab geometry. The Kohn-Sham exact-exchange
      potential V(x)(z) has been generated by using the optimized effective potential
      method, through an accurate numerical solution, imposing the correct boundary
      condition. It has been proved analytically, and confirmed numerically, that
      V(x)(z--> infinity) --> -e(2)/z; this conclusion is not affected by the inclusion
      of correlation effects. Also, the exact-exchange potential develops a
      shoulderlike structure close to the interface, on the vacuum side. The issue of
      the classical image potential is discussed.

PMID- 16907473
TI  - Fingerprints of the magnetic polaron in nonequilibrium electron transport through
      a quantum wire coupled to a ferromagnetic spin chain.
AB  - We study nonequilibrium quantum transport through a mesoscopic wire coupled via
      local exchange to a ferromagnetic spin chain. Using the Keldysh formalism in the
      self-consistent Born approximation, we identify fingerprints of the magnetic
      polaron state formed by hybridization of electronic and magnon states. Because of
      its low decoherence rate, we find coherent transport signals. Both elastic and
      inelastic peaks of the differential conductance are discussed as a function of
      external magnetic fields, the polarization of the leads, and the electronic level
      spacing of the wire.

PMID- 16907474
TI  - Size-dependent effects on electrical contacts to nanotubes and nanowires.
AB  - Metal-semiconductor contacts play a key role in electronics. Here we show that
      for quasi-one-dimensional (Q1D) structures such as nanotubes and nanowires, side
      contact with the metal only leads to weak band realignment, in contrast with bulk
      metal-semiconductor contacts. Schottky barriers are much reduced compared with
      the bulk limit, and should facilitate the formation of good contacts. However,
      the conventional strategy of heavily doping the semiconductor to obtain Ohmic
      contacts breaks down as the nanowire diameter is reduced. The issue of Fermi
      level pinning is also discussed, and it is demonstrated that the unique density
      of states of Q1D structures makes them less sensitive to this effect. Our results
      agree with recent experimental work, and should apply to a broad range of Q1D
      materials.

PMID- 16907475
TI  - Leggett-Garg inequality with a kicked quantum pump.
AB  - A kicked quantum nondemolition measurement is introduced, where a qubit is weakly
      measured by pumping current. Measurement statistics are derived for weak
      measurements combined with single-qubit unitary operations. These results are
      applied to violate a generalization of the Leggett-Garg inequality. The violation
      is related to the failure of the noninvasive detector assumption, and may be
      interpreted as either intrinsic detector backaction, or the qubit entangling the
      microscopic detector excitations. The results are discussed in terms of a quantum
      point contact kicked by a pulse generator, measuring a double quantum dot.

PMID- 16907476
TI  - Probing the superfluid velocity with a superconducting tip: the Doppler shift
      effect.
AB  - We address the question of probing the supercurrents in superconducting (SC)
      samples on a local scale by performing scanning tunneling spectroscopy (STS)
      experiments with a SC tip. In this configuration, we show that the tunneling
      conductance is highly sensitive to the Doppler shift term in the SC quasiparticle
      (QP) spectrum of the sample, thus allowing the local study of the superfluid
      velocity. Intrinsic screening currents, such as those surrounding the vortex
      cores in a type II SC in a magnetic field, are directly probed. With Nb tips, the
      STS mapping of the vortices, in single crystal 2H-NbSe(2), reveals both the
      vortex cores, on the scale of the SC coherence length xi, and the supercurrents,
      on the scale of the London penetration length lambda. A subtle interplay between
      the SC pair potential and the supercurrents at the vortex edge is observed. Our
      results open interesting prospects for the study of screening currents in any
      superconductor.

PMID- 16907477
TI  - Correlation length of quasiperiodic vortex lattices.
AB  - We investigated vortex-lattice dynamics in superconducting Nb thin films with
      different quasiperiodic arrays of magnetic pinning centers. The mixed-state
      magnetoresistance exhibits minima for well-defined applied fields, related to
      matching effects between the vortex lattice and those arrays. The results show
      that critical matching can originate at a local scale. For fractal arrays, the
      vortex-lattice correlation length is longer and the minima are deeper, close to
      those of periodic arrays.

PMID- 16907478
TI  - Remanence due to wall magnetization and counterintuitive magnetometry data in 200
      nm films of Ni.
AB  - 200-nm-thick Ni films in an epitaxial Cu/Ni/Cu/Si(001) structure are expected to
      have an in-plane effective magnetic anisotropy. However, the in-plane remanence
      is only 42%, and magnetic force microscopy domain images suggest perpendicular
      magnetization. Quantitative magnetic force microscopy analysis can resolve the
      inconsistencies and show that (i) the films have perpendicular domains capped by
      closure domains with magnetization canted at 51 degrees from the film normal,
      (ii) the magnetization in the Bloch domain walls between the perpendicular
      domains accounts for the low in-plane remanence, and (iii) the perpendicular
      magnetization process requires a short-range domain wall motion prior to wall
      magnetization rotation and is nonhysteretic, whereas the in-plane magnetization
      requires long-range motion before domain-magnetization rotation and is
      hysteretic.

PMID- 16907479
TI  - Coherent kinetic control over crystal orientation in macroscopic ensembles of
      polymer nanorods and nanotubes.
AB  - We show that the crystal orientation in polymer nanotubes and nanorods inside
      porous templates is controlled by the kinetics of nucleation and growth under 2D
      confinement. Two clear limiting cases are identified: In separated
      nanostructures, any crystal orientation allowing the growth of lamellar crystals
      along the pores appears statistically. If a bulklike surface film connects the
      nanostructures, macroscopic arrays with uniform crystal orientation are obtained,
      in which the dominant growth direction of the crystals is aligned with the long
      axes of the pores of the template.

PMID- 16907480
TI  - Frustrated polyelectrolyte bundles and T= 0 Josephson-junction arrays.
AB  - We establish a one-to-one mapping between a model for hexagonal polyelectrolyte
      bundles and a model for two-dimensional, frustrated Josephson-junction arrays. We
      find that the T = 0 insulator-to-superconductor transition of the quantum system
      corresponds to a continuous liquid-to-solid transition of the condensed charge in
      the finite-temperature classical system. We find that the role of the vector
      potential in the quantum system is played by elastic strain in the classical
      system. Exploiting this correspondence we show that the transition is accompanied
      by a spontaneous breaking of a discrete symmetry associated with the chiral
      patterning of the array and that at the transition the polyelectrolyte bundle
      adopts a universal response to shear.

PMID- 16907481
TI  - What is in a pebble shape?
AB  - We propose to characterize the shapes of flat pebbles in terms of the statistical
      distribution of curvatures measured along the pebble contour. This is
      demonstrated for the erosion of clay pebbles in a controlled laboratory
      apparatus. Photographs at various stages of erosion are analyzed, and compared
      with two models. We find that the curvature distribution complements the usual
      measurement of aspect ratio, and connects naturally to erosion processes that are
      typically faster at protruding regions of high curvature.

PMID- 16907482
TI  - Migration-driven aggregate growth on scale-free networks.
AB  - We study the kinetics of migration-driven aggregate growth on completely
      connected scale-free networks. A reversible migration system is considered with
      the size-dependent rate kernel K(k; l/i;j) approximately k(u)i(v)(lj)(v), at
      which an i-mer aggregate located on the node with j links gains one monomer from
      a k-mer aggregate on the node with l links. The results show that the evolution
      behavior of the aggregate size distribution is drastically different from that
      for the corresponding same system in normal space. This model can be used to
      mimic some phenomena such as the distribution of city populations. Moreover, we
      verify our analytic results in good agreement with the data of the population
      distributions of all U.S. counties.

PMID- 16907483
TI  - Definability of no-return transition states in the high-energy regime above the
      reaction threshold.
AB  - No-return transition states (TSs) defined in multidimensional phase space, where
      recrossing trajectories through the commonly used "configuration" TS pass only
      once, robustly exist up to a moderately high-energy regime above the reaction
      threshold, even when nonlinear resonances among the bath degrees of freedom
      perpendicular to the reaction coordinate result in local chaos. However, at much
      higher energy when global chaos appears in the bath space, the separability of
      the reaction coordinate from the bath degrees of freedom starts to lose locally.
      In the phase space near the saddles, it is found that the slower the system
      passes the TS, the more recrossing trajectories reappear. Their implications and
      mechanisms are discussed concerning to what extent one can define no-return TSs
      in the high-energy regime above the reaction threshold.

PMID- 16907484
TI  - Realistic quantitative descriptions of electron transfer reactions: diabatic free
      energy surfaces from first-principles molecular dynamics.
AB  - A general approach to calculate the diabatic surfaces for electron-transfer
      reactions is presented, based on first-principles molecular dynamics of the
      active centers and their surrounding medium. The excitation energy corresponding
      to the transfer of an electron at any given ionic configuration (the Marcus
      energy gap) is accurately assessed within ground-state density-functional theory
      via a novel penalty functional for oxidation-reduction reactions that
      appropriately acts on the electronic degrees of freedom alone. The self
      interaction error intrinsic to common exchange-correlation functionals is also
      corrected by the same penalty functional. The diabatic free-energy surfaces are
      then constructed from umbrella sampling on large ensembles of configurations. As
      a paradigmatic case study, the self-exchange reaction between ferrous and ferric
      ions in water is studied in detail.

PMID- 16907485
TI  - Faceting and commensurability in crystal structures of colloidal thin films.
AB  - This Letter investigates the influence of finite size effects on the particle
      arrangement of thin film colloidal crystals. A rich variety of crystallographic
      faceting with large single domain microcrystallites is shown. Optical reflectance
      experiments together with scanning electron microscopy permit the identification
      of the crystal symmetry and the facet orientation, as well as the exact number of
      monolayers. When the cell thickness is not commensurable with a high symmetry
      layering, particles arrange themselves in a periodic distribution of (111)- and
      (100)-orientated face centered cubic (fcc) microcrystallites separated by planar
      defects. These structures can be described as a fcc ordering orientated along a
      vicinal surface, modified by a periodic distribution of fcc (111) stacking
      faults.

PMID- 16907486
TI  - Observation of phase separation in a strongly interacting imbalanced fermi gas.
AB  - We have observed phase separation between the superfluid and the normal component
      in a strongly interacting Fermi gas with imbalanced spin populations. The in situ
      distribution of the density difference between two trapped spin components is
      obtained using phase-contrast imaging and 3D image reconstruction. A shell
      structure is clearly identified where the superfluid region of equal densities is
      surrounded by a normal gas of unequal densities. The phase transition induces a
      dramatic change in the density profiles as excess fermions are expelled from the
      superfluid.

PMID- 16907487
TI  - Asymptotic quantum cloning is state estimation.
AB  - The impossibility of perfect cloning and state estimation are two fundamental
      results in quantum mechanics. It has been conjectured that quantum cloning
      becomes equivalent to state estimation in the asymptotic regime where the number
      of clones tends to infinity. We prove this conjecture using two known results of
      quantum information theory: the monogamy of quantum correlations and the
      properties of entanglement breaking channels.

PMID- 16907488
TI  - Unconventional continuous phase transition in a three-dimensional dimer model.
AB  - Phase transitions occupy a central role in physics, due both to their
      experimental ubiquity and their fundamental conceptual importance. The
      explanation of universality at phase transitions was the great success of the
      theory formulated by Ginzburg and Landau, and extended through the
      renormalization group by Wilson. However, recent theoretical suggestions have
      challenged this point of view in certain situations. In this Letter we report the
      first large-scale simulations of a three-dimensional model proposed to be a
      candidate for requiring a description beyond the Landau-Ginzburg-Wilson
      framework: we study the phase transition from the dimer crystal to the Coulomb
      phase in the cubic dimer model. Our numerical results strongly indicate that the
      transition is continuous and is compatible with a tricritical universality class,
      at variance with previous proposals.

PMID- 16907489
TI  - Competing types of order in two-dimensional bose-fermi mixtures.
AB  - Using a functional renormalization group approach we study the zero temperature
      phase diagram of two-dimensional Bose-Fermi mixtures of ultracold atoms in
      optical lattices, in the limit when the velocity of bosonic condensate
      fluctuations is much larger than the Fermi velocity. For spin-1/2 fermions we
      obtain a phase diagram, which shows a competition of pairing phases of various
      orbital symmetry (s, p, and d) and antiferromagnetic order. We determine the
      value of the gaps of various phases close to half filling, and identify
      subdominant orders as well as short-range fluctuations from the renormalization
      group flow. For spinless fermions we find that p-wave pairing dominates the phase
      diagram.

PMID- 16907490
TI  - New measurement of the electron magnetic moment using a one-electron quantum
      cyclotron.
AB  - A new measurement resolves cyclotron and spin levels for a single-electron
      quantum cyclotron to obtain an electron magnetic moment, given by g/2=1.001 159
      652 180 85 (76) [0.76 ppt]. The uncertainty is nearly 6 times lower than in the
      past, and g is shifted downward by 1.7 standard deviations. The new g, with a
      quantum electrodynamics (QED) calculation, determines the fine structure constant
      with a 0.7 ppb uncertainty--10 times smaller than for atom-recoil determinations.
      Remarkably, this 100 mK measurement probes for internal electron structure at 130
      GeV.

PMID- 16907491
TI  - New determination of the fine structure constant from the electron value and QED.
AB  - Quantum electrodynamics (QED) predicts a relationship between the dimensionless
      magnetic moment of the electron (g) and the fine structure constant (alpha). A
      new measurement of g using a one-electron quantum cyclotron, together with a QED
      calculation involving 891 eighth-order Feynman diagrams, determine alpha(
      1)=137.035 999 710 (96) [0.70 ppb]. The uncertainties are 10 times smaller than
      those of nearest rival methods that include atom-recoil measurements. Comparisons
      of measured and calculated g test QED most stringently, and set a limit on
      internal electron structure.

PMID- 16907492
TI  - What mass are the smallest protohalos?
AB  - We calculate the kinetic-decoupling temperature for weakly interacting massive
      particles (WIMPs) in supersymmetric (SUSY) and extra dimensional models that can
      account for the cold-dark-matter abundance determined from cosmic microwave
      background measurements. Depending on the parameters of the particle-physics
      model, a wide variety of decoupling temperatures is possible, ranging from
      several MeV to a few GeV. These decoupling temperatures imply a range of masses
      for the smallest protohalos much larger than previously thought--ranging from 10(
      6)M(+ in a circle) to 10(2)M(+ in a circle). We expect the range of protohalos
      masses derived here to be characteristic of most particle-physics models that can
      thermally accommodate the required relic abundance of WIMP dark matter, even
      beyond SUSY and extra dimensions.

PMID- 16907495
TI  - Critical opalescence in baryonic QCD matter.
AB  - We show that critical opalescence, a clear signature of second-order phase
      transition in conventional matter, manifests itself as critical intermittency in
      QCD matter produced in experiments with nuclei. This behavior is revealed in
      transverse momentum spectra as a pattern of power laws in factorial moments, to
      all orders, associated with baryon production. This phenomenon together with a
      similar effect in the isoscalar sector of pions (sigma mode) provide us with a
      set of observables associated with the search for the QCD critical point in
      experiments with nuclei at high energies.

PMID- 16907496
TI  - Linking confinement to spectral properties of the dirac operator.
AB  - We represent Polyakov loops and their correlators as spectral sums of eigenvalues
      and eigenmodes of the lattice Dirac operator. The deconfinement transition of
      pure gauge theory is characterized as a change in the response of moments of
      eigenvalues to varying the boundary conditions of the Dirac operator. We argue
      that the potential between static quarks is linked to spatial correlations of
      Dirac eigenvectors.

PMID- 16907498
TI  - Normal-incidence electrostatic Rydberg atom mirror.
AB  - A Rydberg atom mirror has been designed and its operational principle tested
      experimentally. A supersonic expansion containing H atoms moving with a velocity
      of 720 m/s initially propagates toward a quadrupolar electrostatic mirror. The H
      atoms are then photoexcited to n=27 Rydberg states with a positive Stark shift
      and move in a rapidly increasing electric field. The H atom beam is stopped in
      4.8 micros, only 1.9 mm away from the photoexcitation spot, and is then reflected
      back. The reflection process is monitored by pulsed field ionization and imaging.

PMID- 16907497
TI  - Anti-stokes laser cooling in bulk erbium-doped materials.
AB  - We report the first observation of anti-Stokes laser-induced cooling in the
      Er3+:KPb2Cl5 crystal and in the Er3+:CNBZn (CdF2-CdCl2-NaF-BaF2-BaCl2-ZnF2)
      glass. The internal cooling efficiencies have been calculated by using
      photothermal deflection spectroscopy. Thermal scans acquired with an infrared
      thermal camera proved the bulk cooling capability of the studied samples. The
      implications of these results are discussed.

PMID- 16907494
TI  - Search for the Theta+ Pentaquark in the gammad--> DeltanK+ reaction measured with
      the CLAS spectrometer.
AB  - For the first time, the reaction gammad-->DeltanK+ has been analyzed in order to
      search for the exotic pentaquark baryon Theta+(1540). The data were taken at
      Jefferson Laboratory, using the Hall-B tagged-photon beam of energy between 0.8
      and 3.6 GeV and the CEBAF Large Acceptance Spectrometer (CLAS). No statistically
      significant structures were observed in the nK+ invariant-mass distribution. The
      upper limit on the gammad-->DeltaTheta+ integrated cross section has been
      calculated and found to be between 5 and 25 nb, depending on the production model
      assumed. The upper limit on the differential cross section is also reported.

PMID- 16907499
TI  - Hybrid quantum processors: molecular ensembles as quantum memory for solid state
      circuits.
AB  - We investigate a hybrid quantum circuit where ensembles of cold polar molecules
      serve as long-lived quantum memories and optical interfaces for solid state
      quantum processors. The quantum memory realized by collective spin states
      (ensemble qubit) is coupled to a high-Q stripline cavity via microwave Raman
      processes. We show that, for convenient trap-surface distances of a few microm,
      strong coupling between the cavity and ensemble qubit can be achieved. We discuss
      basic quantum information protocols, including a swap from the cavity photon bus
      to the molecular quantum memory, and a deterministic two qubit gate. Finally, we
      investigate coherence properties of molecular ensemble quantum bits.

PMID- 16907500
TI  - Effect of the photon's Brownian Doppler shift on the weak-localization coherent
      backscattering cone.
AB  - We report the first observation of the dependence of the coherent-backscattering
      (CBS) enhanced cone with the frequency of the backscattered photon. The
      experiment is performed on a diffusing liquid suspension and the Doppler
      broadening of light is induced by the Brownian motion of the scatterers.
      Heterodyne detection on a CCD camera is used to measure the complex field (i.e.,
      the hologram) of the light that is backscattered at a given frequency. The
      analysis of the holograms yield the frequency and the propagation direction of
      the backscattered photons. We observe that the angular CBS cone becomes more
      narrow in the tail of the Brownian spectrum. The experimental results are in good
      agreement with a simple theoretical model.

PMID- 16907501
TI  - Velocity locking of incoherent nonlinear wave packets.
AB  - We show both theoretically and experimentally in an optical fiber system that a
      set of incoherent nonlinear waves irreversibly evolves to a specific equilibrium
      state, in which the individual wave packets propagate with identical group
      velocities. This intriguing process of velocity locking can be explained in
      detail by simple thermodynamic arguments based on the kinetic wave theory.
      Accordingly, the selection of the velocity-locked state is shown to result from
      the natural tendency of the isolated wave system to approach the state that
      maximizes the nonequilibrium entropy.

PMID- 16907502
TI  - Nonlinearity management in optics: experiment, theory, and simulation.
AB  - We conduct an experimental investigation of nonlinearity management in optics
      using femtosecond pulses and layered Kerr media consisting of glass and air. By
      examining the propagation properties over several diffraction lengths, we show
      that wave collapse can be prevented. We corroborate these experimental results
      with numerical simulations of the (2+1)-dimensional focusing cubic nonlinear
      Schrodinger equation with piecewise constant coefficients and a theoretical
      analysis of this setting using a moment method.

PMID- 16907503
TI  - Nodal domain statistics for quantum maps, percolation, and stochastic Loewner
      evolution.
AB  - We develop a percolation model for nodal domains in the eigenvectors of quantum
      chaotic torus maps. Our model follows directly from the assumption that the
      quantum maps are described by random matrix theory. Its accuracy in predicting
      statistical properties of the nodal domains is demonstrated for perturbed cat
      maps and supports the use of percolation theory to describe the wave functions of
      general Hamiltonian systems. We also demonstrate that the nodal domains of the
      perturbed cat maps obey the Cardy crossing formula and find evidence that the
      boundaries of the nodal domains are described by stochastic Loewner evolution
      with diffusion constant close to the expected value of 6, suggesting that quantum
      chaotic wave functions may exhibit conformal invariance in the semiclassical
      limit.

PMID- 16907504
TI  - Direct numerical simulation of stochastically forced laminar plane couette flow:
      peculiarities of hydrodynamic fluctuations.
AB  - The background of three-dimensional hydrodynamic (vortical) fluctuations in a
      stochastically forced, laminar, incompressible, plane Couette flow is simulated
      numerically. The fluctuating field is anisotropic and has well pronounced
      peculiarities: (i) the hydrodynamic fluctuations exhibit nonexponential,
      transient growth; (ii) fluctuations with the streamwise characteristic length
      scale about 2 times larger than the channel width are predominant in the
      fluctuating spectrum instead of streamwise constant ones; (iii) nonzero cross
      correlations of velocity (even streamwise-spanwise) components appear; (iv)
      stochastic forcing destroys the spanwise reflection symmetry (inherent to the
      linear and full Navier-Stokes equations in a case of the Couette flow) and causes
      an asymmetry of the dynamical processes.

PMID- 16907505
TI  - Incoherent effects of electron clouds in proton storage rings.
AB  - Electron clouds in the beam pipe of high-energy proton or positron storage rings
      can give rise to significant incoherent emittance growth, at densities far below
      the coherent-instability threshold. We identify two responsible mechanisms:
      namely, (1) a beam particle periodically crosses a resonance and (2) a beam
      particle periodically crosses a region of the bunch where its motion is linearly
      unstable. Formation of halo or beam-core blow up, respectively, are the result.
      Key ingredients for both processes are synchrotron motion and electron-induced
      tune shift. The mechanisms considered provide a possible explanation for reduced
      beam lifetime and emittance growth observed at several operating accelerators.
      Similar phenomena are likely to occur in other two-stream systems.

PMID- 16907506
TI  - Opacity measurements of a hot iron plasma using an x-ray laser.
AB  - The temporal evolution of the opacity of an iron plasma at high temperature (30
      350 eV) and high density (0.001-0.2 g cm-3) has been measured using a nickel-like
      silver x-ray laser at 13.9 nm. The hot dense iron plasma was created in a thin
      (50 nm) iron layer buried 80 nm below the surface in a plastic target that was
      heated using a separate 80 ps pulse of 6-9 J, focused to a 100 microm diameter
      spot. The experimental opacities are compared with opacities evaluated from
      plasma conditions predicted using a fluid and atomic physics code.

PMID- 16907507
TI  - Linear perturbation amplification in self-similar ablation flows of inertial
      confinement fusion.
AB  - Exact similarity solutions for inviscid compressible ablative flows in slab
      symmetry with nonlinear heat conduction are proposed for studying unsteadiness
      and compressibility effects on the hydrodynamic stability of ablation fronts
      relevant to inertial confinement fusion. Both the similarity solutions and their
      linear perturbations are numerically computed with a dynamical multidomain
      Chebyshev pseudospectral method. Herewith the first analysis of laser-imprinting
      based on a dynamic solution is presented, showing that maximum perturbation
      amplification occurs for a laser-intensity modulation of zero transverse wave
      number, with growth dominated by the mean flow stretching.

PMID- 16907508
TI  - Evidence for a crossover in the frequency dependence of the acoustic attenuation
      in vitreous silica.
AB  - We report measurements of the sound attenuation coefficient in vitreous silica,
      for sound waves of wavelength between 50 and 80 nm, performed with the new
      inelastic UV light scattering technique. These data indicate that in silica glass
      a crossover between a temperature-dependent (at low frequency) and a temperature
      independent (at high frequency) acoustic attenuation mechanism occurs at Q
      approximately equal to 0.15 nm(-1). The absence of any signature in the static
      structure factor at this Q value suggests that the observed crossover should be
      associated with local elastic constant fluctuations.

PMID- 16907493
TI  - Search for new physics in lepton+photon+X events with 305 pb(-1) of pp collisions
      at [square root of s] = 1.96 TeV.
AB  - We present results of a search for anomalous production of events containing a
      charged lepton (l, either e or mu) and a photon (gamma), both with high
      transverse momentum, accompanied by additional signatures X, including missing
      transverse energy (ET) and additional leptons and photons. We use the same
      selection criteria as in a previous CDF search but with a substantially larger
      data set, 305 pb(-1), a pp collision energy of 1.96 TeV, and the CDF II detector.
      We find 42 lgammaET events versus an expectation of 37.3+/-5.4 events. We observe
      31 llgamma+X events versus an expectation of 23.0+/-2.7 events. We find no events
      similar to the run I eegammagammaET event.

PMID- 16907509
TI  - Behavior of disordered boron carbide under stress.
AB  - Gibbs free-energy calculations based on density functional theory have been used
      to determine the possible source of failure of boron carbide just above the
      Hugoniot elastic limit (HEL). A range of B4C polytypes is found to be stable at
      room pressure. The energetic barrier for shock amorphization of boron carbide is
      by far the lowest for the B12(CCC) polytype, requiring only 6 GPa approximately =
      P(HEL) for collapse under hydrostatic conditions. The results clearly demonstrate
      that the collapse of the B12(CCC) phase leads to segregation of B12 and amorphous
      carbon in the form of 2-3 nm bands along the (113) lattice direction, in
      excellent agreement with recent transmission electron microscopy results.

PMID- 16907510
TI  - Correlations in the elastic response of dense random packings.
AB  - Results are presented for the autocorrelation function of the vortexlike
      nonaffine piece of the linear elastic displacement field in dense random
      bidisperse packings of harmonically repulsive disks in 2D. The autocorrelation
      function is shown to scale precisely with the length of the simulation cell in
      systems ranging from 20 to 100 particles across. It is shown that, to first
      order, the displacement fields can be thought to arise from the action of
      uncorrelated local random forcing of a homogeneous elastic sheet, and a theory is
      presented which gives excellent quantitative agreement with the form of the
      correlation functions. These results suggest measurements to be made in many
      types of densely packed, random materials where the elastic displacement fields
      are accessible experimentally such as granular materials, dense emulsions,
      colloidal suspensions, etc.

PMID- 16907512
TI  - Pressure-induced site-selective disordering of Ge2Sb2Te5: a new insight into
      phase-change optical recording.
AB  - We demonstrate that , the material of choice in phase-change optical recording
      (such as DVD-RAM), can be rendered amorphous by the application of hydrostatic
      pressure. It is argued that this structural change is due to a very strong second
      nearest-neighbor Te-Te interaction that determines the long-range order in the
      metastable cubic phase of and also to the presence of vacancies. This newly
      discovered phenomenon suggests that pressure is an important factor for the
      formation of the amorphous phase which opens new insight into the mechanism of
      phase-change optical recording.

PMID- 16907511
TI  - Volume change during the formation of nanoporous gold by dealloying.
AB  - We report a macroscopic shrinkage by up to 30 vol % during electrochemical
      dealloying of Ag-Au. Since the original crystal lattice is maintained during the
      process, we suggest that the formation of nanoporous gold in our experiments is
      accompanied by the creation of a large number of lattice defects and by local
      plastic deformation.

PMID- 16907513
TI  - Nonequilibrium phase diagram of sticky nanotube suspensions.
AB  - We report a universal phase diagram describing the evolution from solidlike
      networks to flowing nematics for "sticky" nanotube suspensions under an applied
      shear stress. Although the nanotubes are strongly non-Brownian, we find features
      characteristic of first-order phase transitions, including a discontinuity in the
      nematic order parameter at the isotropic-(para)nematic phase boundary. Using
      simple physical arguments, we account for the shape of the coexistence curves, as
      well as the dependence of the order parameter on concentration and stress.

PMID- 16907515
TI  - Oxidation of step edges on Si(001)-c(4x2).
AB  - The initial oxidation process of the ultraclean Si(001)-c(4x2) surface is studied
      using scanning tunneling microscopy at low temperature. At the early stage of
      oxygen adsorption, reactions with Si atoms at SB steps are dominant over those at
      terraces by more than 2 orders of magnitude, and they proceed in two distinct
      stages to high oxidation states. Guided by the ab initio calculations, the
      oxidation structures at each stage are proposed. The extreme reactivity of the
      step edge is due to the presence of rebonded adatoms with dangling bonds and weak
      rebonds, and their proximity allows the formation of -Si-O- chain structures
      along the step edge, unlike those on the Si(111) surface.

PMID- 16907514
TI  - Potential energy landscape of monolayer-surface systems governed by repulsive
      lateral interactions: the case of (3 x 3)-I-Pt(111).
AB  - Combined density functional theory (DFT) and Monte Carlo (MC) approach is applied
      to study the potential energy landscape of four iodine atoms adsorbed on the
      Pt(111) surface in a (3 x 3) unit cell. Three critical points were identified: (3
      x 3)-sym and (3 x 3)-asym, corresponding to structures well known from
      experimental studies, while the third one (3 x 3)-zigzag is a new structure not
      reported before. An interaction model fitted to DFT calculations allows us to
      explain the difference between arrangements of iodine monolayer in vacuum, air,
      and solution environments as a result of different repulsion regimes.

PMID- 16907516
TI  - General theory of amplitude-modulation atomic force microscopy.
AB  - We present a general analytical theory that enables one to determine accurately
      the unknown tip-sample interactions from the experimental measurement of the
      amplitude and phase of the oscillating tip in amplitude-modulation atomic force
      microscopy (AM-AFM). We apply the method to the known Lennard-Jones-type forces
      and find excellent agreement with the reconstructed results. AM-AFM, widely used
      in air and liquid, is now not only an imaging tool but also a quantitative force
      measurement tool.

PMID- 16907517
TI  - Dynamic instability of thin viscoelastic films under lateral stress.
AB  - We study the influence of lateral stress on the stability of thin viscoelastic
      films. The free surface of a deposited film under stress is shown to undergo an
      instability initiated by an anisotropic diffusion of the polymer molecules. This
      instability ultimately results in the formation of holes provided that the
      initial surface fluctuations are larger than a critical value. The latter is
      found to decrease when increasing the stress. An increase of the holes number
      density with the stress is therefore predicted. Most interestingly, the holes
      number density is also predicted to increase when increasing the molecular weight
      of the polymers. Additionally, we demonstrate that the friction of the substrate
      suppresses any spatial coherence between holes on large length scales. These
      predictions explain recent experimental observations made on thin spin-coated
      polystyrene films [G. Reiter, Nat. Mater. 4, 754 (2005)10.1038/nmat1484].

PMID- 16907518
TI  - Bonding trends and dimensionality crossover of gold nanoclusters on metal
      supported MgO thin films.
AB  - Bonding of gold clusters, , 16, and 20, on MgO(100) and on thin MgO films
      supported on Mo(100) is investigated using first-principles density-functional
      theory. Enhanced adhesive bonding is found for clusters deposited on metal
      supported MgO films of thickness up to about 1 nm, or 4 to 5 MgO layers,
      originating from electrostatic interaction between the underlying metal and metal
      induced excess electronic charge accumulated at the cluster interface with the
      oxide film. The increased wetting propensity is accompanied by a dimensionality
      crossover from three-dimensional optimal cluster geometries on MgO(100) to
      energetically favored two-dimensional structures on the metal-supported films.

PMID- 16907519
TI  - Tuning solid surfaces from hydrophobic to superhydrophilic by submonolayer
      surface modification.
AB  - Molecular-scale understanding and manipulation of the wetting behavior of water
      on solids remains a fundamental challenge. Using diamond as a model system, we
      show that the naturally hydrophobic behavior of a hydrogen-terminated C(111)
      surface can be manipulated by replacing the H termination with a monolayer of
      adsorbate. In particular, a mixed monolayer of 1/3 Na and 2/3 F atoms leads to
      superhydrophilic behavior, as shown by first-principles calculations. The
      physical origin of the superhydrophilic behavior is attributed to the ionic
      nature of the Na adatoms, which mediate the right degree of binding strength
      between water molecules and the substrate.

PMID- 16907520
TI  - Pseudogap and antiferromagnetic correlations in the hubbard model.
AB  - Using the dynamical cluster approximation and quantum Monte Carlo simulations we
      calculate the single-particle spectra of the Hubbard model with next-nearest
      neighbor hopping . In the underdoped region, we find that the pseudogap along the
      zone diagonal in the electron doped systems is due to long-range
      antiferromagnetic correlations. The physics in the proximity of (0, pi) is
      dramatically influenced by t' and determined by the short range correlations. The
      effect t' of on the low-energy angle-resolved photoemission spectroscopy spectra
      is weak except close to the zone edge. The short range correlations are
      sufficient to yield a pseudogap signal in the magnetic susceptibility and produce
      a concomitant gap in the single-particle spectra near (pi, pi/2), but not
      necessarily at a location in the proximity of the Fermi surface.

PMID- 16907521
TI  - Green's function of a dressed particle.
AB  - We present a new, highly efficient yet accurate approximation for the Green's
      functions of dressed particles, using the Holstein polaron as an example. Instead
      of summing a subclass of self-energy diagrams (e.g., the noncrossed ones, in the
      self-consistent Born approximation), we sum all the diagrams, but with each
      diagram averaged over its free propagators' momenta. The resulting Green's
      function satisfies exactly the first six spectral weight sum rules. All higher
      sum rules are satisfied with great accuracy, becoming asymptotically exact for
      coupling both much larger and much smaller than the free particle bandwidth.
      Possible generalizations to other models are also discussed.

PMID- 16907522
TI  - Time-dependent density-functional theory beyond the local-density approximation.
AB  - Approximations for the ground-state exchange-correlation potential of density
      functional theory have reached a high level of sophistication. By contrast, time-
      or frequency-dependent exchange-correlation potentials are still being treated in
      a local approximation. Here we propose a novel approximation scheme, which
      effectively brings the power of the generalized gradient approximation (GGA) and
      meta-GGA to time-dependent density-functional theory. The theory should allow a
      more accurate treatment of strongly inhomogeneous electronic systems (e.g.
      molecular junctions) while remaining essentially exact for slowly varying
      densities and slowly varying external potentials.

PMID- 16907523
TI  - Dynamic structure factor of the Calogero-Sutherland model.
AB  - We evaluate the dynamic structure factor S(q, omega) of a one-dimensional quantum
      Hamiltonian with the inverse-square interaction (Calogero-Sutherland model). For
      a fixed small q, the structure factor differs from zero in a finite interval of
      frequencies of the width deltaomega proportional to q2/m. At the borders of this
      interval S(q, omega) exhibits power-law singularities with exponents depending on
      the interaction strength. The singularities are similar in origin to the well
      known Fermi-edge singularity in the x-ray absorption spectra of metals.

PMID- 16907524
TI  - Controlling strong electromagnetic fields at subwavelength scales.
AB  - We investigate the optical response of two subwavelength grooves on a metallic
      screen, separated by a subwavelength distance. We show that the cavity, Fabry
      Perot-like mode, already observed in one-dimensional periodic gratings and known
      for a single slit, splits into two resonances in our system: a symmetric mode
      with a small Q factor, and an antisymmetric one which leads to a much stronger
      field enhancement. This behavior results from the near-field coupling of the
      grooves. Moreover, the use of a second incident wave allows control of the
      localization of the photons in the groove of our choice, depending on the phase
      difference between the two incident waves. The system acts exactly as a
      subwavelength optical switch operated from far field.

PMID- 16907525
TI  - Anisotropic thermopower and planar Nernst effect in Ga1-xMnxAs ferromagnetic
      semiconductors.
AB  - We present the first experimental study of the thermopower in Mn-doped GaAs
      ferromagnetic semiconductors. Large magnetothermopower effects in both
      longitudinal and transverse directions have been observed below the ferromagnetic
      transition temperature. Unlike magnetoresistance, neither the transverse
      thermopower (planar Nernst effect) nor the longitudinal thermopower explicitly
      depend on the strength of the in-plane magnetic field, but rather are intimately
      related to each other through the magnetization. These newly discovered effects
      can be satisfactorily explained by an extension of anisotropic magnetotransport
      model and place important constraints on potential microscopic descriptions of
      the scattering mechanisms in these materials.

PMID- 16907526
TI  - Dynamical disentanglement across a point contact in a non-Abelian quantum Hall
      state.
AB  - We analyze the tunneling of non-Abelian quasiparticles between the edges of a
      quantum Hall droplet at the Landau level filling fraction nu=5/2, assuming that
      the electrons in the first excited Landau level organize themselves in the non
      Abelian Moore-Read Pfaffian state. By bosonizing the edge theory, we show that an
      effective spin-1/2 degree of freedom emerges in the description of a point
      contact. We show how the crossover from the high-temperature regime of weak
      quasiparticle tunneling between the edges of the droplet, with the 4-terminal Rxx
      approximately T(-3/2), to the low-temperature limit, with Rxx(-1/10)(h/e2)
      approximately-T4, is closely related to the two-channel Kondo effect. We give a
      physical interpretation for the entropy loss of ln(2[square root of 2) in this
      crossover.

PMID- 16907527
TI  - Electron localization properties in graphene.
AB  - We study localization properties of the Dirac-like electronic states in
      monolayers of graphite. In the framework of a general disorder model, we discuss
      the conditions under which such standard localization effects as the logarithmic
      temperature-dependent conductivity correction appear to be strongly suppressed,
      as compared to the case of a two-dimensional electron gas with parabolic
      dispersion, in agreement with recent experimental observations.

PMID- 16907528
TI  - Charge carriers in few-layer graphene films.
AB  - The nature of the charge carriers in 2D few-layer graphites (FLGs) has been
      recently questioned by transport measurements [K. S. Novoselov, Science 306, 666
      (2004)10.1126/science.1102896] and a strong ambipolar electric field effect has
      been revealed. Our density functional calculations demonstrate that the
      electronic band dispersion near the Fermi level, and consequently the nature of
      the charge carriers, is highly sensitive to the number of layers and the stacking
      geometry. We show that the experimentally observed ambipolar transport is only
      possible for an FLG with a Bernal-like stacking pattern, whereas simple-carrier
      or semiconducting behavior is predicted for other geometries.

PMID- 16907529
TI  - Transition from free to interacting composite fermions away from.
AB  - Spin excitations from a partially populated composite fermion level are studied
      above and below nu=1/3. In the range 2/7<nu<2/5, the experiments uncover
      significant departures from the noninteracting composite fermion picture that
      demonstrate the increasing impact of interactions as quasiparticle Landau levels
      are filled. The observed onset of a transition from free to interacting composite
      fermions could be linked to condensation into the higher order states suggested
      by transport experiments and numerical evaluations performed in the same filling
      factor range.

PMID- 16907530
TI  - Suppression of spin relaxation in submicron InGaAs wires.
AB  - We investigate electron-spin dynamics in narrow two-dimensional n-InGaAs channels
      as a function of the channel width. The spin relaxation times increase with
      decreasing channel width, in accordance with recent theoretical predictions based
      on the dimensionally constrained D'yakonov-Perel' mechanism. Surprisingly, the
      suppression of the relaxation rate, which is anticipated for the one-dimensional
      limit, is observed for widths that are an order of magnitude larger than the
      electron mean free path. We find the spin precession length and the channel width
      to be the relevant length scales for interpreting these results.

PMID- 16907531
TI  - Electromagnetic response of broken-symmetry nanoscale clusters.
AB  - A microscopic, nonlocal response theory is developed to model the interaction of
      electromagnetic radiation with inhomogeneous nanoscale clusters. The breakdown of
      classical continuum-field Mie theory is demonstrated at a critical coarse
      graining threshold, below which macroscopic plasmon resonances are replaced by
      molecular excitations with suppressed spectral intensity.

PMID- 16907532
TI  - Stability diagram of a few-electron triple dot.
AB  - Individual and coupled quantum dots containing one or two electrons have been
      realized and are regarded as components for future quantum information circuits.
      In this Letter we map out experimentally the stability diagram of the few
      electron triple dot system, the electron configuration map as a function of the
      external tuning parameters, and reveal experimentally for the first time the
      existence of quadruple points, a signature of the three dots being in resonance.
      In the vicinity of these quadruple points we observe a duplication of charge
      transfer transitions related to charge and spin reconfigurations triggered by
      changes in the total electron occupation number. The experimental results are
      largely reproduced by equivalent circuit analysis and Hubbard models. Our results
      are relevant for future quantum mechanical engineering applications within both
      quantum information and quantum cellular automata architectures.

PMID- 16907533
TI  - Quantum spin-Hall effect and topologically invariant Chern numbers.
AB  - We present a topological description of the quantum spin-Hall effect (QSHE) in a
      two-dimensional electron system on a honeycomb lattice with both intrinsic and
      Rashba spin-orbit couplings. We show that the topology of the band insulator can
      be characterized by a 2 x 2 matrix of first Chern integers. The nontrivial QSHE
      phase is identified by the nonzero diagonal matrix elements of the Chern number
      matrix (CNM). A spin Chern number is derived from the CNM, which is conserved in
      the presence of finite disorder scattering and spin nonconserving Rashba
      coupling. By using the Laughlin gedanken experiment, we numerically calculate the
      spin polarization and spin transfer rate of the conducting edge states and
      determine a phase diagram for the QSHE.

PMID- 16907534
TI  - Interference as a probe of spin incoherence in strongly interacting quantum
      wires.
AB  - We show that interference experiments can be used to identify the spin-incoherent
      regime of strongly interacting one-dimensional conductors. Two qualitative
      signatures of spin incoherence are found: a strong magnetic field dependence of
      the interference contrast and an anomalous scaling of the interference contrast
      with the applied voltage, with a temperature and magnetic field dependent scaling
      exponent. The experiments distinguish the spin-incoherent from the spin-polarized
      regime, and so may be useful in deciding between alternative explanations
      proposed for the anomalous conductance quantization observed in quantum point
      contacts and quantum wires at low density.

PMID- 16907535
TI  - Shot-noise signatures of 0.7 structure and spin in a quantum point contact.
AB  - We report simultaneous measurement of shot noise and dc transport in a quantum
      point contact as a function of source-drain bias, gate voltage, and in-plane
      magnetic field. Shot noise at zero field exhibits an asymmetry related to the 0.7
      structure in conductance. The asymmetry in noise evolves smoothly into the
      symmetric signature of spin-resolved electron transmission at high field.
      Comparison to a phenomenological model with density-dependent level splitting
      yields good quantitative agreement.

PMID- 16907536
TI  - Effect of magnetic impurities in a two-band superconductor: a point-contact study
      of mn-substituted single crystals.
AB  - We present the first results of directional point-contact measurements in Mg1
      xMnxB2 single crystals, with x up to 0.015 and bulk Tc down to 13.3 K. The order
      parameters Deltasigma and Deltapi were obtained by fitting the conductance curves
      with the two-band Blonder-Tinkham-Klapwijk model. BothDeltapi and Deltasigma
      decrease with the critical temperature of the junctions TAC, but remain clearly
      distinct up to the highest Mn content. Once analyzed within the Eliashberg
      theory, the results indicate that spin-flip scattering is dominant in the sigma
      band, as also confirmed by first-principles band-structure calculations.

PMID- 16907537
TI  - Anisotropic drude response and the effect of anisotropic C substitution in.
AB  - The in-plane and the out-of-plane optical spectra of small single crystals of
      Mg(B1-xCx)2 were directly determined by a microscope spectroscopy technique.
      Contrary to previous reports, the estimated plasma frequencies for both
      directions are quite consistent with the band calculation. A multi-Drude picture
      corresponding to a multiband system is necessary to explain the whole spectral
      profile. The spectral changes with the carbon substitution indicate a decrease of
      carrier concentration as well as an increase of scattering rate, particularly, in
      the sigma bands.

PMID- 16907538
TI  - Significant enhancement of ferromagnetism in Zn1-xCrxTe doped with iodine as an n
      type dopant.
AB  - The effect of additional doping of charge impurities was investigated in a
      ferromagnetic semiconductor Zn1-xCrxTe. It was found that the doping of iodine,
      which is expected to act as an n-type dopant in ZnTe, brought about a drastic
      enhancement of the ferromagnetism in Zn1-xCrxTe, while the grown films remained
      electrically insulating. In particular, at a fixed Cr composition of x=0.05, the
      ferromagnetic transition temperature TC increased up to 300 K at maximum due to
      the iodine doping from TC=30 K of the undoped counterpart, while the
      ferromagnetism disappeared due to the doping of nitrogen as a p-type dopant. The
      observed systematic correlation of ferromagnetism with the doping of charge
      impurities of both the p and n type, suggesting a key role of the position of
      Fermi level within the impurity d state, is discussed on the basis of the double
      exchange interaction as a mechanism of ferromagnetism in this material.

PMID- 16907539
TI  - Intrinsic colossal magnetoresistance effect in thin-film Pr0.5Sr0.5MnO3 through
      dimensionality switching.
AB  - A homogeneous colossal magnetoresistance (CMR) effect at low temperatures has
      been found in a thin-film perovskite manganite Pr0.5Sr0.5MnO3. The transition is
      driven not by the spin alignment as in usual CMR in bulk samples but by the
      localization-delocalization transition switched by the change in the effective
      dimensionality. Two-dimensional (x2-y2)-orbital ordering enhanced by the
      substrate strain is essential for the stabilization of the insulating localized
      state, which is on the verge of the first-order transition to the three
      dimensional metallic ferromangetic state.

PMID- 16907540
TI  - Direct kinetic correlation of carriers and ferromagnetism in Co2+: ZnO.
AB  - The hypothesis that high-Curie-temperature ferromagnetism in cobalt-doped ZnO
      (Co2+: ZnO) is mediated by charge carriers was tested by controlled introduction
      and removal of the shallow donor interstitial zinc. Using oriented epitaxial
      Co2+: ZnO films grown by chemical vapor deposition, kinetics measurements
      demonstrate a direct correlation between the oxidative quenching of
      ferromagnetism and the diffusion and oxidation of interstitial zinc. These
      results demonstrate controlled systematic variation of a key parameter involved
      in the ferromagnetism of Co2+: ZnO and, in the process, unambiguously reveal this
      ferromagnetism to be dependent upon charge carriers. The distinction between
      defect-bound and free carriers in Co2+: ZnO is discussed.

PMID- 16907541
TI  - Numerical modeling of the central spin problem using the spin-coherent-state
      representation.
AB  - In this work, we consider decoherence of a central spin by a spin bath. In order
      to study the nonperturbative decoherence regimes, we develop an efficient mean
      field-based method for modeling the spin-bath decoherence, based on the
      representation of the central spin density matrix. The method can be applied to
      longitudinal and transverse relaxation at different external fields. In
      particular, by modeling large-size quantum systems (up to 16 000 bath spins), we
      make controlled predictions for the slow long-time decoherence of the central
      spin.

PMID- 16907542
TI  - Ultrafast band-gap shift induced by a strain pulse in semiconductor
      heterostructures.
AB  - The conventional piezospectroscopic effect is extended to picosecond time scales
      by using ultrashort strain pulses injected into semiconductor heterostructures.
      The strain pulses with durations of approximately 10 ps are generated in a metal
      transducer film by intense femtosecond laser pulses. They propagate coherently in
      the GaAs/(Al,Ga)As heterostructure over a distance of 100 microm and shift the
      band gaps by several meV as detected optically for quantum well exciton
      resonances by pump-probe techniques and time-resolved photoluminescence.

PMID- 16907543
TI  - Effect of symmetry distortions on photoelectron selection rules and spectra of
      Bi2Sr2CaCu2O8+delta.
AB  - We derive photoelectron selection rules along the glide plane in orthorhombic
      Bi2Sr2CaCu2O8+delta (Bi2212). These selection rules explain the reversed
      intensity behavior of the shadow and the main band of the material as a natural
      consequence of the variating representation of the final state as a function of
      k(parallel). Our one-step simulations strongly support the structural origin of
      the shadow band but we also introduce a scenario for detecting antiferromagnetic
      signatures in low doping.

PMID- 16907544
TI  - Dynamically induced effective interaction in periodically driven granular
      mixtures.
AB  - We show that a granular mixture subject to horizontal oscillations can be reduced
      to a monodisperse system of particles interacting via an effective interaction.
      This interaction is attractive at short distances and strongly anisotropic, and
      its features explain the system rich phenomenology, including segregation and
      stripe pattern formation. Finally, we show that a modified Cahn-Hilliard
      equation, which takes into account the characteristics of the effective
      interaction, is capable of describing the dynamics of the mixture.

PMID- 16907545
TI  - Collective dynamics of interacting molecular motors.
AB  - The collective dynamics of N interacting processive molecular motors are
      considered theoretically when an external force is applied to the leading motor.
      We show, using a discrete lattice model, that the force-velocity curves strongly
      depend on the effective dynamic interactions between motors and differ
      significantly from those of a simple approach where the motors equally share the
      force. Moreover, they become essentially independent of the number of motors if N
      is large enough (N> or approximately 5 for conventional kinesin). We show that a
      two-state ratchet model has a very similar behavior to that of the coarse-grained
      lattice model with effective interactions. The general picture is unaffected by
      motor attachment and detachment events.

PMID- 16907547
TI  - Optothermal molecule trapping by opposing fluid flow with thermophoretic drift.
AB  - Thermophoresis moves molecules along temperature gradients, typically from hot to
      cold. We superpose fluid flow with thermophoretic molecule flow under well
      defined microfluidic conditions, imaged by fluorescence microscopy. DNA is
      trapped and accumulated 16-fold in regions where both flows oppose each other.
      Strong 800-fold accumulation is expected, however, with slow trapping kinetics.
      The experiment is equally described by a three-dimensional and one-dimensional
      analytical model. As an application, we show how a radially converging
      temperature field confines short DNA into a 10 microm small spot.

PMID- 16907546
TI  - Lateral membrane waves constitute a universal dynamic pattern of motile cells.
AB  - We have monitored active movements of the cell circumference on specifically
      coated substrates for a variety of cells including mouse embryonic fibroblasts
      and T cells, as well as wing disk cells from fruit flies. Despite having
      different functions and being from multiple phyla, these cell types share a
      common spatiotemporal pattern in their normal membrane velocity; we show that
      protrusion and retraction events are organized in lateral waves along the cell
      membrane. These wave patterns indicate both spatial and temporal long-range
      periodic correlations of the actomyosin gel.

PMID- 16907548
TI  - Suppression of thermally excited capillary waves by shear flow.
AB  - We investigate the thermal fluctuations of the colloidal gas-liquid interface
      subjected to a shear flow parallel to the interface. Strikingly, we find that the
      shear strongly suppresses capillary waves, making the interface smoother. This
      phenomenon can be described by introducing an effective interfacial tension that
      increases with the shear rate. The increase of sigma(eff) is a direct consequence
      of the loss of interfacial entropy caused by the flow, which affects especially
      the slow fluctuations. This demonstrates that the interfacial tension of fluids
      results from an intrinsic as well as a fluctuation contribution.

PMID- 16907549
TI  - Two-dimensional foam rheology with viscous drag.
AB  - We formulate and apply a continuum model that incorporates elasticity, yield
      stress, plasticity, and viscous drag. It is motivated by the two-dimensional foam
      rheology experiments of Debregeas et al. [Phys. Rev. Lett. 87, 178305
      (2001)10.1103/PhysRevLett.87.178305] and Wang et al. [Phys. Rev. E 73, 031401
      (2006)10.1103/PhysRevE.73.031401], and is successful in exhibiting their
      principal features, which are an exponentially decaying velocity profile and
      strain localization. Transient effects are also identified.

PMID- 16907550
TI  - Rhythmic cluster generation in strongly driven colloidal dispersions.
AB  - We study the response of a nematic colloidal dispersion of rods to a driven probe
      particle which is dragged with high speed through the dispersion perpendicular to
      the nematic director. In front of the dragged particle, clusters of rods are
      generated which rhythmically grow and dissolve by rotational motion. We find
      evidence for a mesoscopic cluster-cluster correlation length, independent of the
      imposed drag speed. Our results are based on nonequilibrium Brownian dynamics
      computer simulations and in line with a dynamical scaling theory.

PMID- 16907551
TI  - Comment on "effects of thickness on the spin susceptibility of the two
      dimensional electron gas".

PMID- 16907553
TI  - Berry phase effects on the dynamics of quasiparticles in a superfluid with a
      vortex.
AB  - We study quasiparticle dynamics in a Bose-Einstein condensate with a vortex by
      following the center of mass motion of a Bogoliubov wave packet, and find
      important Berry-phase effects due to the background flow. We show that the Berry
      phase invalidates the usual canonical relation between the mechanical momentum
      and position variables, leading to important modifications of quasiparticle
      statistics and thermodynamic properties of the condensates. Applying these
      results to a vortex in an infinite uniform superfluid, we find that the total
      transverse force acting on the vortex is proportional to the superfluid density.
      We propose an experimental setup to directly observe Berry phase effects through
      measuring local thermal atoms' momentum distribution around a vortex.

PMID- 16907554
TI  - Laser-induced spatial symmetry breaking in quantum and classical mechanics.
AB  - Phase-controllable transport in laser-irradiated spatially symmetric systems is
      shown to arise both quantum mechanically and classically from a common field
      driven interference mechanism. Specifically, the quantum-to-classical transition
      for symmetry breaking in a quartic oscillator driven by an omega+2omega field is
      studied. For this, a double perturbation theory in the oscillator anharmonicity
      and external field strength, that admits an analytic classical limit, is carried
      out in the Heisenberg picture. The interferences responsible for the symmetry
      breaking are shown to survive in the classical limit and are the origins of
      classical control. Differences between reflection symmetry that plays a key role
      in the analysis, and parity that does not, are discussed.

PMID- 16907555
TI  - Decoherence by correlated noise and quantum error correction.
AB  - We study the decoherence of a quantum computer in an environment which is
      inherently correlated in time and space. We first derive the nonunitary time
      evolution of the computer and environment in the presence of a stabilizer error
      correction code, providing a general way to quantify decoherence for a quantum
      computer. The general theory is then applied to the spin-boson model. Our results
      demonstrate that effects of long-range correlations can be systematically reduced
      by small changes in the error correction codes.

PMID- 16907556
TI  - Binary projective measurement via linear optics and photon counting.
AB  - We investigate the implementation of binary projective measurements with linear
      optics. This problem can be viewed as a single-shot discrimination of two
      orthogonal pure quantum states. We show that any two orthogonal states can be
      perfectly discriminated using only linear optics, photon counting, coherent
      ancillary states, and feedforward. The statement holds in the asymptotic limit of
      a large number of these physical resources.

PMID- 16907557
TI  - Robust entanglement through macroscopic quantum jumps.
AB  - We propose an entanglement generation scheme that requires neither the coherent
      evolution of a quantum system nor the detection of single photons. Instead, the
      desired state is heralded by a macroscopic quantum jump. Macroscopic quantum
      jumps manifest themselves as a random telegraph signal with long intervals of
      intense fluorescence (light periods) interrupted by the complete absence of
      photons (dark periods). Here we show that a system of two atoms trapped inside an
      optical cavity can be designed such that a dark period prepares the atoms in a
      maximally entangled ground state. Achieving fidelities above 0.9 is possible even
      when the single-atom cooperativity parameter is as low as 10 and when using a
      photon detector with an efficiency as low as eta=0.2.

PMID- 16907558
TI  - Preserving coherence in Rydberg quantum bits.
AB  - The effectiveness of decoherence suppression schemes is explored using quantum
      bits (qubits) stored in Li np Rydberg states. Following laser excitation, pulsed
      electric fields coherently control the electronic spin-orbit coupling,
      facilitating qubit creation, manipulation, and measurement. Spin-orbit coupling
      creates an approximate decoherence-free subspace for extending qubit storage
      times. However, sequences of fast NOT operations are found to be substantially
      more effective for preserving coherence.

PMID- 16907559
TI  - Ultrafast coherent excitation of a trapped ion qubit for fast gates and photon
      frequency qubits.
AB  - We demonstrate ultrafast coherent excitation of an atomic qubit stored in the
      hyperfine levels of a single trapped cadmium ion. Such ultrafast excitation is
      crucial for entangling networks of remotely located trapped ions through the
      interference of photon frequency qubits, and is also a key component for
      realizing ultrafast quantum gates between Coulomb-coupled ions.

PMID- 16907560
TI  - High-accuracy calculation of the blackbody radiation shift in the 133Cs primary
      frequency standard.
AB  - The blackbody radiation (BBR) shift is an important systematic correction for the
      atomic frequency standards realizing the SI unit of time. Presently, there is
      controversy over the value of the BBR shift for the primary 133Cs standard. At
      room temperatures, the values from various groups differ at the 3x10(-15) level,
      while modern clocks are aiming at 10(-16) accuracies. We carry out high-precision
      relativistic many-body calculations of the BBR shift. For the BBR coefficient
      beta at T=300 K, we obtain beta=-(1.710+/-0.006)x10(-14), implying 6x10(-17)
      fractional uncertainty. While in accord with the most accurate measurement, our
      0.35% accurate value is in a substantial (10%) disagreement with recent
      semiempirical calculations. We identify an oversight in those calculations.

PMID- 16907561
TI  - Frequency shift of the cesium clock transition due to blackbody radiation.
AB  - We perform ab initio calculations of the frequency shift induced by a static
      electric field on the cesium clock hyperfine transition. The calculations are
      used to find the frequency shifts due to blackbody radiation. Our result
      [deltanu/E2=-2.26(2)x10(-10) Hz/(V/m)2] is in good agreement with early
      measurements and ab initio calculations performed in other groups. We present
      arguments against recent claims that the actual value of the effect might be
      smaller. The difference (approximately 10%) between ab initio and semiempirical
      calculations is due to the contribution of the continuum spectrum in the sum over
      intermediate states.

PMID- 16907562
TI  - Can gravity distinguish between Dirac and Majorana neutrinos?
AB  - We show that spin-gravity interaction can distinguish between Dirac and Majorana
      neutrino wave packets propagating in a Lense-Thirring background. Using time
      independent perturbation theory and the gravitational phase to generate a
      perturbation Hamiltonian with spin-gravity coupling, we show that the associated
      matrix element for the Majorana neutrino differs significantly from its Dirac
      counterpart. This difference can be demonstrated through significant
      gravitational corrections to the neutrino oscillation length for a two-flavor
      system, as shown explicitly for SN 1987A.

PMID- 16907563
TI  - Is cosmology compatible with sterile neutrinos?
AB  - By combining data from cosmic microwave background experiments (including the
      recent WMAP third year results), large scale structure, and Lyman-alpha forest
      observations, we constrain the hypothesis of a fourth, sterile, massive neutrino.
      For the 3 massless+1 massive neutrino case, we bound the mass of the sterile
      neutrino to ms<0.26 eV (0.44 eV) at 95% (99.9%) C.L., which excludes at high
      significance the sterile neutrino hypothesis as an explanation of the LSND
      anomaly. We generalize the analysis to account for active neutrino masses and the
      possibility that the sterile abundance is not thermal. In the latter case, the
      contraints in the plane are nontrivial. For a mass of >1 or <0.05 eV, the
      cosmological energy density in sterile neutrinos is always constrained to be
      omeganu<0.003 at 95% C.L., but for a mass of approximately 0.25 eV, omeganu can
      be as large as 0.01.

PMID- 16907564
TI  - Black hole radiance, short distances, and TeV gravity.
AB  - Using a derivation of black hole radiance in terms of two-point functions one can
      provide a quantitative estimate of the contribution of short distances to the
      spectrum. Thermality is preserved for black holes with kappalp<<1. However,
      deviations from the Planckian spectrum can be found for mini black holes in TeV
      gravity scenarios, even before reaching the Planck phase.

PMID- 16907565
TI  - Twisted flavors and tribimaximal neutrino mixing.
AB  - A new framework for handling flavor symmetry breaking in the neutrino sector is
      discussed where the source of symmetry breaking is traced to the global property
      of right-handed neutrinos in extra-dimensional space. Light neutrino
      phenomenology has rich and robust predictions such as the tribimaximal form of
      generation mixing, controlled mass spectrum, and no need of flavor mixing
      couplings in the theory.

PMID- 16907566
TI  - Proposal for a supersymmetric standard model.
AB  - The fact that neutrinos are massive suggests that the minimal supersymmetric
      standard model (MSSM) might be extended in order to include three gauge-singlet
      neutrino superfields with Yukawa couplings of the type H2Lnuc. We propose to use
      these superfields to solve the mu problem of the MSSM without having to introduce
      an extra singlet superfield as in the case of the next-to-MSSM (NMSSM). In
      particular, terms of the type nuc H1H2 in the superpotential may carry out this
      task spontaneously through neutrino vacuum expectation values. In addition, terms
      of the type (nuc)3 avoid the presence of axions and generate effective Majorana
      masses for neutrinos at the electroweak scale. On the other hand, these terms
      break lepton number and R parity explicitly. For Dirac masses of the neutrinos of
      order 10(-4) GeV, eigenvalues reproducing the correct scale of neutrino masses
      are obtained.

PMID- 16907567
TI  - Strong-coupling constant with flavor thresholds at five loops in the modified
      minimal-subtraction scheme.
AB  - We present in analytic form the matching conditions for the strong-coupling
      constant alphas(nf) (mu) at the flavor thresholds to four loops in the modified
      minimal-subtraction scheme. Taking into account the present knowledge on the
      coefficient beta4 of the Callan-Symanzik beta function of quantum chromodynamics,
      we thus derive a five-loop formula for alphas(nf) (mu) together with appropriate
      relationships between the asymptotic scale parameters Lamda(nf) for different
      numbers of flavors nf.

PMID- 16907568
TI  - Proton enhancement at large pT at the CERN large hadron collider without
      structure in associated-particle distribution.
AB  - The production of pions and protons in the pT range between 10 and 20 GeV/c for
      Pb+Pb collisions at CERN LHC is studied in the recombination model. It is shown
      that the dominant mechanism for hadronization is the recombination of shower
      partons from neighboring jets when the jet density is high. Protons are more
      copiously produced than pions in that pT range because the coalescing partons can
      have lower momentum fractions, but no thermal partons are involved. The proton-to
      pion ratio can be as high as 20. When such high pT hadrons are used as trigger
      particles, there will not be any associated particles that are not in the
      background.

PMID- 16907569
TI  - Resonance-assisted decay of nondispersive wave packets.
AB  - We present a quantitative semiclassical theory for the decay of nondispersive
      electronic wave packets in driven, ionizing Rydberg systems. Statistically robust
      quantities are extracted combining resonance-assisted tunneling with subsequent
      transport across chaotic phase space and a final ionization step.

PMID- 16907570
TI  - Electric-field-induced symmetry breaking of angular momentum distribution in
      atoms.
AB  - We report the experimental observation of alignment to orientation conversion in
      the 7D3/2 and 9D3/2 states of Cs in the presence of an external dc electric field
      and without the influence of magnetic fields or atomic collisions. Initial
      alignment of angular momentum states was created by two-step excitation with
      linearly polarized laser radiation. The appearance of transverse orientation of
      angular momentum was confirmed by the observation of circularly polarized light.
      We present experimentally measured signals and compare them with the results of a
      detailed theoretical model based on the optical Bloch equations. The effect is
      odd under time reversal and should be taken into account in ever more sensitive
      searches for an electron electric dipole moment.

PMID- 16907571
TI  - Mass spectrometric investigation of anions formed upon free electron attachment
      to nucleobase molecules and clusters embedded in superfluid helium droplets.
AB  - Here we report the first mass spectrometric study of negative ions formed via
      free electron attachment (EA) to nucleobases (NBs) embedded in helium clusters.
      Pure and mixed clusters of adenine and thymine have been formed by pickup of
      isolated NB molecules by cold helium droplets. In contrast to EA of isolated
      molecules in the gas phase we observe a long-lived parent anion NB- and, in
      addition, parent cluster ions NB-n up to size n=6. Moreover, we show that a low
      energy electron penetrating into a doped helium droplet causes efficient damage
      of the embedded nucleobases via resonant, site selective, dissociative electron
      attachment.

PMID- 16907572
TI  - Nondipole ionization dynamics of atoms in superintense high-frequency attosecond
      pulses.
AB  - The ionization of H(1s) in superintense, high-frequency, attosecond pulses is
      studied beyond the dipole approximation. We identify a unique nondipole 3rd lobe
      in the angular distribution of the ejected electron and show that this lobe has a
      well-defined classical counterpart. The ionization is likely to occur in the
      direction opposite to the laser propagation direction, which is fully understood
      from an analysis of the classical dynamics.

PMID- 16907573
TI  - Direct, loss-tolerant characterization of nonclassical photon statistics.
AB  - We experimentally investigate a method of directly characterizing the photon
      number distribution of nonclassical light beams that is tolerant to losses and
      makes use of only standard binary detectors. This is achieved in a single
      measurement by calibrating the detector using some small amount of prior
      information about the source. We demonstrate the technique on a freely
      propagating heralded two-photon-number state created by conditional detection of
      a two-mode squeezed state generated by parametric down-conversion.

PMID- 16907574
TI  - Geometrical optics of beams with vortices: Berry phase and orbital angular
      momentum Hall effect.
AB  - We consider propagation of a paraxial beam carrying the spin angular momentum
      (polarization) and intrinsic orbital angular momentum (IOAM) in a smoothly
      inhomogeneous isotropic medium. It is shown that the presence of IOAM can
      dramatically enhance and rearrange the topological phenomena that previously were
      considered solely in connection to the polarization of transverse waves. In
      particular, the appearance of a new type of Berry phase that describes the
      parallel transport of the beam structure along a curved ray is predicted. We
      derive the ray equations demonstrating the splitting of beams with different
      values of IOAM. This is the orbital angular momentum Hall effect, which resembles
      the Magnus effect for optical vortices. Unlike the spin Hall effect of photons,
      it can be much larger in magnitude and is inherent to waves of any nature.
      Experimental means to detect the phenomena are discussed.

PMID- 16907575
TI  - Hybrid approach to high-frequency microfluidic mixing.
AB  - We report the experimental verification of the predicted chaotic mixing
      characteristics for a polydimethylsioxane microfluidic chip, based on the
      mechanism of multistage cross-channel flows. While chaotic mixing can be achieved
      within short passage distances, there is an optimal side channel flow pulsation
      frequency beyond which the mixing becomes ineffective. Based on the physical
      understanding of a Poincare section analysis, we propose the installation of
      passive flow baffles in the main microfluidic channel to facilitate high
      frequency mixing. The combined hybrid approach enables chaotic mixing at enhanced
      frequency and reduced passage distance in two-dimensional flows.

PMID- 16907576
TI  - Asymptotics of large bound states of localized structures.
AB  - We analyze stationary fronts connecting uniform and periodic states emerging from
      a pattern-forming instability. The size of the resulting periodic domains cannot
      be predicted with weakly nonlinear methods. We show that what determine this size
      are exponentially small (but exponentially growing in space) terms. These can
      only be computed by going beyond all orders of the usual multiple-scale
      expansion. We apply the method to the Swift-Hohenberg equation and derive
      analytically a snaking bifurcation curve. At each fold of this bifurcation curve,
      a new pair of peaks is added to the periodic domain, which can thus be seen as a
      bound state of localized structures. Such scenarios have been reported with
      optical localized structures in nonlinear cavities and localized buckling.

PMID- 16907577
TI  - Intermittent magnetic field excitation by a turbulent flow of liquid sodium.
AB  - The magnetic field measured in the Madison dynamo experiment shows intermittent
      periods of growth when an axial magnetic field is applied. The geometry of the
      intermittent field is consistent with the fastest-growing magnetic eigenmode
      predicted by kinematic dynamo theory using a laminar model of the mean flow.
      Though the eigenmodes of the mean flow are decaying, it is postulated that
      turbulent fluctuations of the velocity field change the flow geometry such that
      the eigenmode growth rate is temporarily positive. Therefore, it is expected that
      a characteristic of the onset of a turbulent dynamo is magnetic intermittency.

PMID- 16907578
TI  - Drag reduction on a patterned superhydrophobic surface.
AB  - We present an experimental study of a low-Reynolds number shear flow between two
      surfaces, one of which has a regular grooved texture augmented with a
      superhydrophobic coating. The combination reduces the effective fluid-surface
      contact area, thereby appreciably decreasing the drag on the surface and
      effectively changing the macroscopic boundary condition on the surface from no
      slip to limited slip. We measure the force on the surface and the velocity field
      in the immediate vicinity on the surface (and thus the wall shear)
      simultaneously. The latter facilitates a direct assessment of the effective slip
      length associated with the drag reduction.

PMID- 16907579
TI  - Observation of resonant diffusive radiation in random multilayered systems.
AB  - Diffusive radiation is a new type of radiation predicted to occur in randomly
      inhomogeneous media due to the multiple scattering of pseudophotons. This
      theoretical effect is now observed experimentally. The radiation is generated by
      the passage of electrons of energy 200 KeV-2.2 MeV through a random stack of
      films in the visible light region. The radiation intensity increases resonantly
      provided the Cerenkov condition is satisfied for the average dielectric constant
      of the medium. The observed angular dependence and electron resonance energy are
      in agreement with the theoretical predictions. These observations open a road to
      application of diffusive radiation in particle detection, astrophysics, soft-x
      ray generation, etc.

PMID- 16907580
TI  - Proton radiography of a laser-driven implosion.
AB  - Protons accelerated by a picosecond laser pulse have been used to radiograph a
      500 microm diameter capsule, imploded with 300 J of laser light in 6
      symmetrically incident beams of wavelength 1.054 microm and pulse length 1 ns.
      Point projection proton backlighting was used to characterize the density
      gradients at discrete times through the implosion. Asymmetries were diagnosed
      both during the early and stagnation stages of the implosion. Comparison with
      analytic scattering theory and simple Monte Carlo simulations were consistent
      with a 3+/-1 g/cm3 core with diameter 85+/-10 microm. Scaling simulations show
      that protons>50 MeV are required to diagnose asymmetry in ignition scale
      conditions.

PMID- 16907581
TI  - Three-wave interactions between fast-ion modes in the National Spherical Torus
      Experiment.
AB  - Simultaneous bursts of energetic particle mode (EPM) and toroidicity-induced
      Alfven eigenmode (TAE) activity that correlate with significant fast-ion loss are
      observed in beam heated plasmas. Three-wave interactions between these modes are
      conclusively identified, indicating fixed phase relationships. This nonlinear
      coupling concentrates the energy of the TAEs into a toroidally localized
      perturbation frozen in the frame of a rigid, toroidally rotating structure formed
      by the EPMs. This redistribution of energy is significant because it will modify
      the effect of the TAEs on fast-ion loss.

PMID- 16907582
TI  - Theory for formation of a low-pressure, current-free double layer.
AB  - A diffusion-controlled theory is developed for the formation of a low-pressure,
      current-free double layer just inside an upstream insulating source chamber
      connected to a larger diameter, downstream chamber. The double layer is described
      using four groups of charged particles: thermal ions, monoenergetic accelerated
      ions flowing downstream, accelerated electrons flowing upstream, and thermal
      electrons. The condition of particle balance upstream is found to determine the
      double layer potential. The double layer disappears at very low pressures due to
      loss of ionization balance upstream and due to energy relaxation processes for
      ionizing electrons at higher pressures, in good agreement with experiments.

PMID- 16907583
TI  - Active stabilization of the resistive-wall mode in high-beta, low-rotation
      plasmas.
AB  - The resistive-wall mode is actively stabilized in the National Spherical Torus
      Experiment in high-beta plasmas rotating significantly below the critical
      rotation speed for passive stability and in the range predicted for the
      International Thermonuclear Experimental Reactor. Variation of feedback
      stabilization parameters shows mode excitation or suppression. Stabilization of
      toroidal mode number unity did not lead to instability of toroidal mode number
      two. The mode can become unstable by deforming poloidally, an important
      consideration for stabilization system design.

PMID- 16907584
TI  - Analytical model for ion acceleration by high-intensity laser pulses.
AB  - We present a general expression for the maximum ion energy observed in
      experiments with thin foils irradiated by high-intensity laser pulses. The
      analytical model is based on a radially confined surface charge set up by laser
      accelerated electrons on the target rear side. The only input parameters are the
      properties of the laser pulse and the target thickness. The predicted maximum ion
      energy and the optimal laser pulse duration are supported by dedicated
      experiments for a broad range of different ions.

PMID- 16907585
TI  - Properties of geodesic acoustic modes and the relation to density fluctuations.
AB  - The geodesic acoustic mode (GAM) is a high frequency branch of zonal flows, which
      is observed in toroidal plasmas. Because of toroidal curvature effects, density
      fluctuations are excited, which are investigated with the O-mode correlation
      reflectometer at TEXTOR. This Letter reports on the poloidal distribution of GAM
      induced density fluctuation and compares them with theoretical predictions. The
      influence of the GAM flows on the ambient turbulence is studied, too.

PMID- 16907586
TI  - Superfluidity and quantum melting of p-H2 clusters.
AB  - Structural and superfluid properties of p-H2 clusters of size up to N=40
      molecules, are studied at low temperature (0.5 K<or=T<or=4 K) by path integral
      Monte Carlo simulations. The superfluid fraction rhoS(T) displays an interesting,
      nonmonotonic behavior for 22<or=N<or=30. We interpret this dependence in terms of
      variations with N of the cluster structure. Superfluidity is observed at low T in
      clusters of as many as 27 molecules; in the temperature range considered here,
      quantum melting is observed in some clusters, which are seen to freeze at high
      temperature.

PMID- 16907587
TI  - Phonon-induced polariton superlattices.
AB  - We show that the coherent interaction between microcavity polaritons and
      externally stimulated acoustic phonons forms a tunable polariton superlattice
      with a folded energy dispersion determined by the phonon population and
      wavelength. Under high phonon concentration, the strong confinement of the
      optical and excitonic polariton components in the phonon potential creates weakly
      coupled polariton wires with a virtually flat energy dispersion.

PMID- 16907588
TI  - Influence of confinement on the fragility of antiplasticized and pure polymer
      films.
AB  - We investigate by molecular dynamics simulation how thin film confinement
      modifies the fragility of a model glass-forming liquid characterized previously
      in the bulk. Film confinement is found to reduce the relative fragility of the
      polymer fluid, leading to effects similar to simulations of the addition of an
      antiplasticizer additive. A reduction of fragility is not observed for the
      antiplasticized polymer film. These effects are interpreted in terms of variation
      in the string (cooperatively moving segments) concentration with film confinement
      and the addition of antiplasticizing additives.

PMID- 16907589
TI  - Complementary control by additives of the kinetics of amorphous CaCO3
      mineralization at an organic interface: in-situ synchrotron x-ray observations.
AB  - The kinetics of biomimetic mineralization at a fatty acid monolayer interface
      have been measured in situ by synchrotron x-ray reflectivity. The formation of
      biologically relevant amorphous calcium carbonate films is affected by soluble
      macromolecules, supersaturation rate of change, and Mg cations. We find that
      these solution conditions influence mineral film formation in a complementary
      fashion. Poly(sodium acrylate) extends the lifetime of metastable amorphous
      calcium carbonate, solution saturation controls the mineral film growth rate, and
      Mg cations create a longer induction time. This is the first quantification of
      potentially competitive biomineralization mechanisms that addresses nucleation
      and growth of the amorphous mineral phases, which are important in
      biomineralization.

PMID- 16907590
TI  - High-pressure phases of silane.
AB  - High-pressure phases of silane SiH4 are predicted using first-principles
      electronic structure methods. We search for low-enthalpy structures by relaxing
      from randomly chosen initial configurations, a strategy which is demonstrated to
      work well for unit cells containing up to at least ten atoms. We predict that
      silane will metallize at higher pressures than previously anticipated but might
      show high-temperature superconductivity at experimentally accessible pressures.

PMID- 16907591
TI  - Do methanethiol adsorbates on the Au(111) surface dissociate?
AB  - The interaction of methanethiol molecules CH3SH with the Au(111) surface is
      investigated, and it is found for the first time that the S-H bond remains intact
      when the methanethiol molecules are adsorbed on the regular Au(111) surface.
      However, it breaks if defects are present in the Au(111) surface. At low
      coverage, the fcc region is favored for S atom adsorption, but at saturated
      coverage the adsorption energies at various sites are almost isoenergetic. The
      presented calculations show that a methanethiol layer on the regular Au(111)
      surface does not dimerize.

PMID- 16907592
TI  - Quantum smectic as a dislocation Higgs phase.
AB  - The theory describing quantum smectics in 2+1 dimensions, based on topological
      quantum melting is presented. This is governed by a dislocation condensate
      characterized by an ordering of Burger's vector and this "dual shear
      superconductor" manifests itself in the form of a novel spectrum of phononlike
      modes.

PMID- 16907593
TI  - Oxygen-deficient line defects in an ultrathin aluminum oxide film.
AB  - A model for the straight antiphase domain boundary of the ultrathin aluminum
      oxide film on the NiAl(110) substrate is derived from scanning tunneling
      microscopy measurements and density-functional theory calculations. Although the
      local bonding environment of the perfect film is maintained, the structure is
      oxygen deficient and possesses a favorable adsorption site. The domain boundary
      exhibits a downwards band bending and three characteristic unoccupied electronic
      states, in excellent agreement with scanning tunneling spectroscopy measurements.

PMID- 16907594
TI  - Charge inversion at minute electrolyte concentrations.
AB  - Anionic dimyristoylphosphatidic acid monolayers spread on LaCl3 solutions reveal
      strong cation adsorption and a sharp transition to surface overcharging at
      unexpectedly low bulk salt concentrations. We determine the surface accumulation
      of La3+ with anomalous x-ray reflectivity and find that La3+ compensates the
      lipid surface charge by forming a Stern layer with approximately 1 La3+ ion per 3
      lipids below a critical bulk concentration, ct approximately 500 nM. Above ct,
      the surface concentration of La3+ increases to a saturation level with
      approximately 1 La3+ per lipid, thus implying that the total electric charge of
      the La3+ exceeds the surface charge. This overcharge is observed at approximately
      4 orders of magnitude lower concentration than predicted in ion-ion correlation
      theories. We suggest that transverse electrostatic correlations between mobile
      ions and surface charges (interfacial Bjerrum pairing) may contribute to the
      charge inversion.

PMID- 16907595
TI  - Two-stage rotation mechanism for group-V precursor dissociation on Si(001).
AB  - We report ab initio identification of initial dissociation pathways for Sb4 and
      Bi4 tetramer precursors on Si(001). We reveal a two-stage double piecewise
      rotation mechanism for the tetramer to ad-dimer conversion involving two distinct
      pathways: one along the surface dimer row via a rhombus intermediate state and
      the other across the surface dimer row via a rotated rhombus intermediate state.
      These two-stage double piecewise rotation processes play a key role in lowering
      the kinetic barrier by establishing and maintaining energetically favorable
      bonding between adatoms and substrate atoms. These results provide an excellent
      account for experimental observations and elucidate their underlying atomistic
      origin that may offer useful insights for other surface reaction processes.

PMID- 16907596
TI  - Searching for alloy configurations with target physical properties: impurity
      design via a genetic algorithm inverse band structure approach.
AB  - The ability to artificially grow different configurations of semiconductor alloys
      -random structures, spontaneously ordered and layered superlattices--raises the
      issue of how different alloy configurations may lead to new and different alloy
      physical properties. We address this question in the context of nitrogen
      impurities in GaP, which form deep levels in the gap whose energy and optical
      absorption sensitively depend on configuration. We use the "inverse band
      structure" approach in which we first specify a desired target physical property
      (such as the deepest nitrogen level, or lowest strain configuration), and then we
      search, via genetic algorithm, for the alloy atomic configurations that have this
      property. We discover the essential structural motifs leading to such target
      properties. This strategy opens the way to efficient alloy design.

PMID- 16907597
TI  - Mott transition, antiferromagnetism, and d-wave superconductivity in two
      dimensional organic conductors.
AB  - We study the Mott transition, antiferromagnetism, and superconductivity in
      layered organic conductors using the cellular dynamical mean-field theory for the
      frustrated Hubbard model. A d-wave superconducting phase appears between an
      antiferromagnetic insulator and a metal for t'/t=0.3-0.7 or between a nonmagnetic
      Mott insulator (spin liquid) and a metal for t'/t>or=0.8, in agreement with
      experiments on layered organic conductors including kappa-(ET)2Cu2(CN)3. These
      phases are separated by a strong first-order transition. The phase diagram gives
      much insight into the mechanism for -wave superconductivity. Two predictions are
      made.

PMID- 16907598
TI  - Can correlations drive a band insulator metallic?
AB  - We analyze the effects of the on-site Coulomb repulsion U on a band insulator
      using dynamical mean field theory (DMFT). We find the surprising result that the
      gap is suppressed to zero at a critical Uc1 and remains zero within a metallic
      phase. At a larger Uc2 there is a second transition from the metal to a Mott
      insulator, in which the gap increases with increasing U. These results are
      qualitatively different from Hartree-Fock theory which gives a monotonically
      decreasing but nonzero insulating gap for all finite U.

PMID- 16907599
TI  - Electron-phonon interaction and antiferromagnetic correlations.
AB  - We study effects of the Coulomb repulsion on the electron-phonon interaction
      (EPI) in the Holstein-Hubbard model, using the antiferromagnetic (AF) dynamical
      mean-field approximation. AF correlations strongly enhance EPI effects on the
      electron Green's function with respect to the paramagnetic correlated system, but
      the net effect of the Coulomb interaction is a moderate suppression of the EPI.
      Doping leads to additional suppression. In contrast, the Coulomb interaction
      strongly suppresses EPI effects on phonons, but the suppression weakens with
      doping.

PMID- 16907600
TI  - Scaling behavior in thermoelectric misfit cobalt oxides.
AB  - We investigate both thermoelectric and thermodynamic properties of the misfit
      cobalt oxide [Bi1.7Co0.3Ca2O4]RS0.6CoO2. A large negative magnetothermopower is
      found to scale with both magnetic field and temperature, revealing a significant
      spin entropy contribution to thermoelectric properties giving rise to a constant
      S0 approximately 60 microV K-1. Specific heat measurements allow us to determine
      an enhanced electronic part with gamma approximately 50 mJ (mol K2)-1 attesting
      to strong correlations. Thereby, the comparison between cobaltites and other
      materials reveals a universal behavior of the thermopower slope as a function of
      gamma, testifying to a purely electronic origin. This potentially generic scaling
      behavior suggests here that the high room temperature value of the thermopower in
      misfit cobalt oxides results from the addition of a spin entropy contribution to
      an enlarged electronic one.

PMID- 16907601
TI  - Temperature dependence of the spin torque effect in current-induced domain wall
      motion.
AB  - We present an experimental study of domain wall motion induced by current pulses
      as well as by conventional magnetic fields at temperatures between 2 and 300 K in
      a 110 nm wide and 34 nm thick Ni80Fe20 ring. We observe that, in contrast with
      field-induced domain wall motion, which is a thermally activated process, the
      critical current density for current-induced domain wall motion increases with
      increasing temperature, which implies a reduction of the spin torque efficiency.
      The effect of Joule heating due to the current pulses is measured and taken into
      account to obtain critical fields and current densities at constant sample
      temperatures. This allows for a comparison of our results with theory.

PMID- 16907602
TI  - Classical nuclear motion in quantum transport.
AB  - An ab initio quantum-classical mixed scheme for the time evolution of electrode
      device-electrode systems is introduced to study nuclear dynamics in quantum
      transport. Two model systems are discussed to illustrate the method. Our results
      provide the first example of current-induced molecular desorption as obtained
      from a full time-dependent approach and suggest the use of ac biases as a way to
      tailor electromigration. They also show the importance of nonadiabatic effects
      for ultrafast phenomena in nanodevices.

PMID- 16907603
TI  - Vertex corrections to the anomalous Hall effect in spin-polarized two-dimensional
      electron gases with a Rashba spin-orbit interaction.
AB  - We study the effect of disorder on the intrinsic anomalous Hall conductivity in a
      magnetic two-dimensional electron gas with a Rashba-type spin-orbit interaction.
      We find that anomalous Hall conductivity vanishes unless the lifetime is spin
      dependent, similar to the spin Hall conductivity in the nonmagnetic system. In
      addition, we find that the spin Hall conductivity does not vanish in the presence
      of magnetic scatterers.

PMID- 16907604
TI  - Metal-insulator transition tuned by external gates in Hall systems with
      constrictions.
AB  - The nature of a metal-insulator transition tuned by external gates in quantum
      Hall systems with point constrictions, as reported in recent experiments [S.
      Roddaro, Phys. Rev. Lett. 95, 156804 (2005)10.1103/PhysRevLett.95.156804], is
      examined. We attribute this phenomenon to a splitting of the integer edge into
      conducting and insulating stripes, the latter wide enough to allow for the
      stability of the edge structure. Interchannel impurity scattering and
      interchannel Coulomb interactions do not destabilize this picture.

PMID- 16907605
TI  - "Textbook" adsorption at "nontextbook" adsorption sites: halogen atoms on alkali
      halide surfaces.
AB  - Density-functional theory and second order Moller-Plesset perturbation theory
      calculations indicate that halogen atoms bond preferentially to halide substrate
      atoms on a series of alkali halide surfaces, rather than to the alkali atoms as
      might be anticipated. An analysis of the electronic structures in each system
      reveals that this novel adsorption mode is stabilized by the formation of
      textbook two-center three-electron covalent bonds. The implications of these
      findings to, for example, nanostructure crystal growth, are briefly discussed.

PMID- 16907606
TI  - Exact relations between multifractal exponents at the Anderson transition.
AB  - Two exact relations between mutlifractal exponents are shown to hold at the
      critical point of the Anderson localization transition. The first relation
      implies a symmetry of the multifractal spectrum linking the exponents with
      indices q<1/2 to those with q>1/2. The second relation connects the wave-function
      multifractality to that of Wigner delay times in a system with a lead attached.

PMID- 16907607
TI  - Coexistence of triplet superconductivity and spin density waves.
AB  - We discuss the possibility of the coexistence of spin density waves
      (antiferromagnetism) and triplet superconductivity as a particular example of a
      broad class of systems where the interplay of magnetism and superconductivity is
      important. We focus on the case of quasi-one-dimensional metals, where it is
      known that antiferromagnetism is in close proximity to triplet superconductivity
      in the pressure versus temperature phase diagram. Over a range of pressures, we
      propose an intermediate nonuniform phase consisting of antiferromagnetic and
      triplet superconducting orders. In the coexistence region, we propose a flop
      transition in the spin density wave order parameter vector, which affects the
      nature of the superconducting state and leads to the appearance of several new
      phases.

PMID- 16907608
TI  - Predicted magnetoelectric effect in Fe/BaTiO3 multilayers: ferroelectric control
      of magnetism.
AB  - An unexplored physical mechanism which produces a magnetoelectric effect in
      ferroelectric-ferromagnetic multilayers is studied based on first-principles
      calculations. Its origin is a change in bonding at the ferroelectric-ferromagnet
      interface that alters the interface magnetization when the electric polarization
      reverses. Using Fe/BaTiO3 multilayers as a representative model, we show a
      sizable difference in magnetic moments of Fe and Ti atoms at the two interfaces
      dissimilar by the orientation of the local electric dipole moments. The predicted
      magnetoelectric effect opens a new direction to control magnetic properties of
      thin-film layered structures by electric fields.

PMID- 16907609
TI  - First-principles combinatorial design of transition temperatures in
      multicomponent systems: the case of Mn in GaAs.
AB  - The transition temperature TC of multicomponent systems--ferromagnetic,
      superconducting, or ferroelectric--depends strongly on the atomic arrangement,
      but an exhaustive search of all configurations for those that optimize TC is
      difficult, due to the astronomically large number of possibilities. Here we
      address this problem by parametrizing the TC of a set of approximately 50 input
      configurations, calculated from first principles, in terms of configuration
      variables ("cluster expansion"). Once established, this expansion allows us to
      search almost effortlessly the transition temperature of arbitrary
      configurations. We apply this approach to search for the configuration of Mn
      dopants in GaAs having the highest ferromagnetic Curie temperature. Our general
      approach of cluster expanding physical properties opens the way to design based
      on exploring a large space of configurations.

PMID- 16907610
TI  - Neutron spin-echo investigation of slow spin dynamics in kagome-bilayer
      frustrated magnets as evidence for phonon assisted relaxation in SrCr9xGa12
      9xO19.
AB  - A neutron spin-echo investigation of the low temperature spin dynamics in two
      well-characterized kagome bilayer compounds SrCr9xGa12-9xO19 (x=0.95, SCGO) and
      Ba2Sn2ZnCr7xGa10-7xO22 (x=0.97, BSZCGO) reveals two novel features. One is the
      slowing down of the relaxation rate without critical behavior at Tg, where a
      macroscopic spin-glass-like freezing occurs. The second is, in SCGO at 4 K
      (approximately Tg)<T<7 K, the relaxation rate activation energy Ea=7+/-0.4 meV,
      equal to the energy of a phonon mode, pointing out the role of spin-lattice
      coupling.

PMID- 16907611
TI  - Spin waves in quasiequilibrium spin systems.
AB  - Using the Landau Fermi liquid theory we discovered a new propagating transverse
      spin wave in a paramagnetic system which is driven slightly out of equilibrium
      without applying an external magnetic field. We find a gapless mode which
      describes the uniform precession of the magnetization in the absence of a
      magnetic field. We also find a gapped mode associated with the precession of the
      spin current around the internal field. The gapless mode has a quadratic
      dispersion leading to a T3/2 contribution to the specific heat. These modes
      significantly contribute to the dynamic structure function.

PMID- 16907612
TI  - Role of d electrons in Auger neutralization at metal surfaces.
AB  - A generalized theory of Auger electron transfer processes in the interaction of
      ions with metal surfaces, including the previously ignored role of d electrons is
      presented. It is shown that a correct and accurate description of Auger
      neutralization has to account for the contribution of d electrons, as this is
      illustrated on the case of He+ ion neutralization on Ag, where the neglect of
      these leads to a strong overestimation of ion survival probabilities. Crystal
      lattice site specific rates are calculated and allow for a correct description of
      crystal azimuthal effects in neutralization.

PMID- 16907613
TI  - Temperature effects on threshold counterion concentration to induce aggregation
      of fd virus.
AB  - We seek to elucidate the dominant mechanism of attractive interaction between
      like-charged biopolymers by measuring the temperature dependence of the critical
      divalent counterion concentration (Cc) for the aggregation of fd viruses. A
      decrease in either temperature or the dieletric constant alone causes a decrease
      in Cc, providing evidence for the Wigner crystal model. Surprisingly, the effects
      of these two parameters can be combined so that Cc is expressed as a function of
      a single parameter: the Bjerrum length. Cc decreases exponentially as the Bjerrum
      length increases, suggesting that an energetic balance between the entropic
      effect of counterions and the counterion mediated attractive interaction gives
      rise to the onset of bundle formation.

PMID- 16907614
TI  - Transition to bursting via deterministic chaos.
AB  - We study statistical properties of the irregular bursting arising in a class of
      neuronal models close to the transition from spiking to bursting. Prior to the
      transition to bursting, the systems in this class develop chaotic attractors,
      which generate irregular spiking. The chaotic spiking gives rise to irregular
      bursting. The duration of bursts near the transition can be very long. We
      describe the statistics of the number of spikes and the interspike interval
      distributions within one burst as functions of the distance from criticality.

PMID- 16907615
TI  - Dispersion relation of lipid membrane shape fluctuations by neutron spin-echo
      spectrometry.
AB  - We have studied the mesoscopic shape fluctuations in aligned multilamellar stacks
      of 1,2-dimyristoyl-sn-glycero-3-phoshatidylcholine bilayers using the neutron
      spin-echo technique. The corresponding in plane dispersion relation tau-1(q//) at
      different temperatures in the gel (ripple, Pbeta') and the fluid (Lalpha) phase
      of this model system has been determined. Two relaxation processes, one at about
      10 ns and a second, slower process at about 100 ns can be quantified. The
      dispersion relation in the fluid phase is fitted to a smectic hydrodynamic
      theory, with a correction for finite qz resolution. We extract values for the
      bilayer bending rigidity kappa, the compressional modulus of the stacks B, and
      the effective sliding viscosity eta3. The softening of a mode which can be
      associated with the formation of the ripple structure is observed close to the
      main phase transition.

PMID- 16907616
TI  - Gradient learning in spiking neural networks by dynamic perturbation of
      conductances.
AB  - We present a method of estimating the gradient of an objective function with
      respect to the synaptic weights of a spiking neural network. The method works by
      measuring the fluctuations in the objective function in response to dynamic
      perturbation of the membrane conductances of the neurons. It is compatible with
      recurrent networks of conductance-based model neurons with dynamic synapses. The
      method can be interpreted as a biologically plausible synaptic learning rule, if
      the dynamic perturbations are generated by a special class of "empiric" synapses
      driven by random spike trains from an external source.

PMID- 16907617
TI  - Interspecies stress in momentum equations for dense binary particulate systems.
AB  - For two-species particulate systems, ensemble averaged continuity and momentum
      equations for each species are derived based on the Liouville equation of the
      system. The ensemble average used is species specific. It is found that the
      interaction between species results in not only the interspecies force but also a
      stress in the momentum equations. In the limit that particles of one of the
      species can be considered as a continuum, the existence of the interspecies
      stress enables us to reduce the derived equations to the familiar form for
      dispersed two-phase flows.

PMID- 16907618
TI  - Single molecule measurements of repressor protein 1D diffusion on DNA.
AB  - We used single-molecule imaging techniques and measured the one-dimensional
      diffusion of LacI repressor proteins along elongated DNA to address the long
      standing puzzle of why some proteins find their targets faster than allowed by 3D
      diffusion. Our analysis of the LacI transcription factor's diffusion yielded four
      main results: (1) LacI diffuses along nonspecific sequences of DNA in the form of
      1D Brownian motion; (2) the observed 1D diffusion coefficients D1vary over an
      unexpectedly large range, from 2.3x10(-12) cm2/s to 1.3x10(-9) cm2/s; (3) the
      lengths of DNA covered by these 1D diffusions vary from 120 nm to 2920 nm; and
      (4) the mean values of D1 and the diffusional lengths indeed predict a LacI
      target binding rate 90 times faster than the 3D diffusion limit.

PMID- 16907619
TI  - Caustic activation of rain showers.
AB  - We show quantitatively how the collision rate of droplets of visible moisture in
      turbulent air increases very abruptly as the intensity of the turbulence passes a
      threshold, due to the formation of fold caustics in their velocity field. The
      formation of caustics is an activated process, in which a measure of the
      intensity of the turbulence, termed the Stokes number St, is analogous to
      temperature in a chemical reaction: the rate of collision contains a factor exp(
      C/St). Our results are relevant to the long-standing problem of explaining the
      rapid onset of rainfall from convecting clouds. Our theory does not involve
      spatial clustering of particles.

PMID- 16907620
TI  - Cognitive ability experiment with photosensitive organic molecular thin films.
AB  - We present an optical experiment which permits us to evaluate the information
      exchange necessary to self-induce cooperatively a well-organized pattern in a
      randomly activated molecular assembly. A low-power coherent beam carrying
      polarization and wavelength information is used to organize a surface relief
      grating on a photochromic polymer thin film which is photoactivated by a powerful
      incoherent beam. We demonstrate experimentally that less than 1% of the molecules
      possessing information cooperatively transmit it to the entire photoactivated
      polymer film.

PMID- 16907621
TI  - Comment on "correlation quantum dynamics between an electron and D2+ molecule
      with attosecond resolution".

PMID- 16907623
TI  - Comment on "spin correlations in the paramagnetic phase and ring exchange in
      La2CuO4".

PMID- 16907625
TI  - Educating to improve population health outcomes in chronic disease: an innovative
      workforce initiative across remote, rural and Indigenous communities in northern
      Australia.
AB  - INTRODUCTION: Like Indigenous populations in other countries, an epidemic of
      chronic disease has swept across Australia's Indigenous communities in the past
      decade. The Northern Territory and Queensland health departments initiated
      preventable chronic disease strategies in 1999 and 2001, respectively. Yet
      finding innovative ways to translate this to the health workforce was
      challenging. Through support from the Australian Government, three universities,
      two health departments and two Indigenous organisations worked in partnership to
      improve workforce capacity in remote and rural communities through innovative
      education. METHODS: The methods included: (i) a training needs analysis
      consisting of 76 semi-structured interviews with key informants, and 35 surveys
      of remote staff; (ii) a literature and resource review; (iii) the development of
      a curriculum framework using: the existing competencies and standards across the
      health disciplines; the identified workforce needs; and what the workforce can
      impact upon; (iv) a multidisciplinary workshop with 35 educators across northern
      Australia that resulted in the basis for agreement of the final curriculum
      content and framework; (v) the development of a chronic disease self-assessment
      tool that was piloted with remote health staff; (vi) an assisted integration
      process for key stakeholders. An evaluation framework was also developed, as a
      separate project, in conjunction with the project partners during this time.
      RESULTS: This project identified that a paradigm shift is required in the way in
      which we educate the entire health workforce to deal effectively with the impact
      of chronic disease across remote, rural and Indigenous populations. In particular
      a need was found to educate the educators in the chronic care model and in using
      a population health approach. The training needs analysis identified very little
      difference between the education and training needs across the rural and remote
      health disciplines; it was perceived that they managed chronic disease fairly
      well yet found prevention and early detection to be at the 'hard end'. The main
      barriers identified were the demands of acute care over chronic disease
      management, compounded by high workforce turnover in remote areas. The curriculum
      framework, in particular the domains of remote practice, is being used by several
      Australian universities, health departments and non-government organisations in
      adapting their existing or new education programs. The self-assessment tool was
      based on the curriculum outcomes and was piloted in 2005 and found to be very
      useful for pre- and post-training purposes and as a discussion starter for all
      disciplines and groups. CONCLUSIONS: A practical curriculum framework now exists
      to integrate a population health approach for the prevention and early detection
      of chronic disease when educating the primary healthcare workforce. It is
      relevant to all health disciplines and is flexible in that it can be adapted, or
      adopted, depending on the educational needs of the disciplinary group. It is
      being imbedded into numerous undergraduate, postgraduate, and professional
      development programs in Australia. It includes: the core learning outcomes
      expected of any workforce, resources, and a self-assessment tool in chronic
      disease. These tools are assisting educators in the required paradigm shift
      required of the workforce to alter the single disease based practice model
      towards a comprehensive and integrated population based approach required for the
      workforce in the 21st century.

PMID- 16907626
TI  - Consistency of pseudolikelihood estimation of fully visible Boltzmann machines.
AB  - A Boltzmann machine is a classic model of neural computation, and a number of
      methods have been proposed for its estimation. Most methods are plagued by either
      very slow convergence or asymptotic bias in the resulting estimates. Here we
      consider estimation in the basic case of fully visible Boltzmann machines. We
      show that the old principle of pseudolikelihood estimation provides an estimator
      that is computationally very simple yet statistically consistent.

PMID- 16907627
TI  - Images, frames, and connectionist hierarchies.
AB  - The representation of hierarchically structured knowledge in systems using
      distributed patterns of activity is an abiding concern for the connectionist
      solution of cognitively rich problems. Here, we use statistical unsupervised
      learning to consider semantic aspects of structured knowledge representation. We
      meld unsupervised learning notions formulated for multilinear models with tensor
      product ideas for representing rich information. We apply the model to images of
      faces.

PMID- 16907628
TI  - Properties of synergies arising from a theory of optimal motor behavior.
AB  - We consider the properties of motor components, also known as synergies, arising
      from a computational theory (in the sense of Marr, 1982) of optimal motor
      behavior. An actor's goals were formalized as cost functions, and the optimal
      control signals minimizing the cost functions were calculated. Optimal synergies
      were derived from these optimal control signals using a variant of nonnegative
      matrix factorization. This was done using two different simulated two--joint arms
      -an arm controlled directly by torques applied at the joints and an arm in which
      forces were applied by muscles--and two types of motor tasks-reaching tasks and
      via-point tasks. Studies of the motor synergies reveal several interesting
      findings. First, optimal motor actions can be generated by summing a small number
      of scaled and time-shifted motor synergies, indicating that optimal movements can
      be planned in a low-dimensional space by using optimal motor synergies as motor
      primitives or building blocks. Second, some optimal synergies are task
      independent--they arise regardless of the task context-whereas other synergies
      are task dependent--they arise in the context of one task but not in the contexts
      of other tasks. Biological organisms use a combination of task--independent and
      task--dependent synergies. Our work suggests that this may be an efficient
      combination for generating optimal motor actions from motor primitives. Third,
      optimal motor actions can be rapidly acquired by learning new linear combinations
      of optimal motor synergies. This result provides further evidence that optimal
      motor synergies are useful motor primitives. Fourth, synergies with similar
      properties arise regardless if one uses an arm controlled by torques applied at
      the joints or an arm controlled by muscles, suggesting that synergies, when
      considered in "movement space," are more a reflection of task goals and
      constraints than of fine details of the underlying hardware.

PMID- 16907629
TI  - Recognition by variance: learning rules for spatiotemporal patterns.
AB  - Recognizing specific spatiotemporal patterns of activity, which take place at
      timescales much larger than the synaptic transmission and membrane time
      constants, is a demand from the nervous system exemplified, for instance, by
      auditory processing. We consider the total synaptic input that a single readout
      neuron receives on presentation of spatiotemporal spiking input patterns. Relying
      on the monotonic relation between the mean and the variance of a neuron's input
      current and its spiking output, we derive learning rules that increase the
      variance of the input current evoked by learned patterns relative to that
      obtained from random background patterns. We demonstrate that the model can
      successfully recognize a large number of patterns and exhibits a slow
      deterioration in performance with increasing number of learned patterns. In
      addition, robustness to time warping of the input patterns is revealed to be an
      emergent property of the model. Using a leaky integrate-and-fire realization of
      the readout neuron, we demonstrate that the above results also apply when
      considering spiking output.

PMID- 16907630
TI  - Estimating spiking irregularities under changing environments.
AB  - We considered a gamma distribution of interspike intervals as a statistical model
      for neuronal spike generation. A gamma distribution is a natural extension of the
      Poisson process taking the effect of a refractory period into account. The model
      is specified by two parameters: a time-dependent firing rate and a shape
      parameter that characterizes spiking irregularities of individual neurons.
      Because the environment changes over time, observed data are generated from a
      model with a time-dependent firing rate, which is an unknown function. A
      statistical model with an unknown function is called a semiparametric model and
      is generally very difficult to solve. We used a novel method of estimating
      functions in information geometry to estimate the shape parameter without
      estimating the unknown function. We obtained an optimal estimating function
      analytically for the shape parameter independent of the functional form of the
      firing rate. This estimation is efficient without Fisher information loss and
      better than maximum likelihood estimation. We suggest a measure of spiking
      irregularity based on the estimating function, which may be useful for
      characterizing individual neurons in changing environments.

PMID- 16907631
TI  - Spatiotemporal structure in large neuronal networks detected from cross
      correlation.
AB  - The analysis of neuronal information involves the detection of spatiotemporal
      relations between neuronal discharges. We propose a method that is based on the
      positions (phase offsets) of the central peaks obtained from pairwise cross
      correlation histograms. Data complexity is reduced to a one-dimensional
      representation by using redundancies in the measured phase offsets such that each
      unit is assigned a "preferred firing time" relative to the other units in the
      group. We propose two procedures to examine the applicability of this method to
      experimental data sets. In addition, we propose methods that help the
      investigation of dynamical changes in the preferred firing times of the units.
      All methods are applied to a sample data set obtained from cat visual cortex.

PMID- 16907632
TI  - Stable competitive dynamics emerge from multispike interactions in a stochastic
      model of spike-timing-dependent plasticity.
AB  - In earlier work we presented a stochastic model of spike-timing-dependent
      plasticity (STDP) in which STDP emerges only at the level of temporal or spatial
      synaptic ensembles. We derived the two-spike interaction function from this model
      and showed that it exhibits an STDP-like form. Here, we extend this work by
      examining the general n-spike interaction functions that may be derived from the
      model. A comparison between the two-spike interaction function and the higher
      order interaction functions reveals profound differences. In particular, we show
      that the two-spike interaction function cannot support stable, competitive
      synaptic plasticity, such as that seen during neuronal development, without
      including modifications designed specifically to stabilize its behavior. In
      contrast, we show that all the higher-order interaction functions exhibit a fixed
      point structure consistent with the presence of competitive synaptic dynamics.
      This difference originates in the unification of our proposed "switch" mechanism
      for synaptic plasticity, coupling synaptic depression and synaptic potentiation
      processes together. While three or more spikes are required to probe this
      coupling, two spikes can never do so. We conclude that this coupling is critical
      to the presence of competitive dynamics and that multispike interactions are
      therefore vital to understanding synaptic competition.

PMID- 16907633
TI  - A state-space analysis for reconstruction of goal-directed movements using neural
      signals.
AB  - The execution of reaching movements involves the coordinated activity of multiple
      brain regions that relate variously to the desired target and a path of arm
      states to achieve that target. These arm states may represent positions,
      velocities, torques, or other quantities. Estimation has been previously applied
      to neural activity in reconstructing the target separately from the path.
      However, the target and path are not independent. Because arm movements are
      limited by finite muscle contractility, knowledge of the target constrains the
      path of states that leads to the target. In this letter, we derive and illustrate
      a state equation to capture this basic dependency between target and path. The
      solution is described for discrete-time linear systems and gaussian increments
      with known target arrival time. The resulting analysis enables the use of
      estimation to study how brain regions that relate variously to target and path
      together specify a trajectory. The corresponding reconstruction procedure may
      also be useful in brain-driven prosthetic devices to generate control signals for
      goal-directed movements.

PMID- 16907634
TI  - What is the relation between slow feature analysis and independent component
      analysis?
AB  - We present an analytical comparison between linear slow feature analysis and
      second-order independent component analysis, and show that in the case of one
      time delay, the two approaches are equivalent. We also consider the case of
      several time delays and discuss two possible extensions of slow feature analysis.

PMID- 16907635
TI  - Nonlocal estimation of manifold structure.
AB  - We claim and present arguments to the effect that a large class of manifold
      learning algorithms that are essentially local and can be framed as kernel
      learning algorithms will suffer from the curse of dimensionality, at the
      dimension of the true underlying manifold. This observation invites an
      exploration of nonlocal manifold learning algorithms that attempt to discover
      shared structure in the tangent planes at different positions. A training
      criterion for such an algorithm is proposed, and experiments estimating a tangent
      plane prediction function are presented, showing its advantages with respect to
      local manifold learning algorithms: it is able to generalize very far from
      training data (on learning handwritten character image rotations), where local
      nonparametric methods fail.

PMID- 16907636
TI  - Dynamics and topographic organization of recursive self-organizing maps.
AB  - Recently there has been an outburst of interest in extending topographic maps of
      vectorial data to more general data structures, such as sequences or trees.
      However, there is no general consensus as to how best to process sequences using
      topographic maps, and this topic remains an active focus of neurocomputational
      research. The representational capabilities and internal representations of the
      models are not well understood. Here, we rigorously analyze a generalization of
      the self-organizing map (SOM) for processing sequential data, recursive
      SOM(RecSOM) (Voegtlin, 2002), as a nonautonomous dynamical system consisting of a
      set of fixed input maps. We argue that contractive fixed-input maps are likely to
      produce Markovian organizations of receptive fields on the RecSOM map. We derive
      bounds on parameter beta (weighting the importance of importing past information
      when processing sequences) under which contractiveness of the fixed-input maps is
      guaranteed. Some generalizations of SOM contain a dynamic module responsible for
      processing temporal contexts as an integral part of the model. We show that
      Markovian topographic maps of sequential data can be produced using a simple
      fixed (nonadaptable) dynamic module externally feeding a standard topographic
      model designed to process static vectorial data of fixed dimensionality (e.g.,
      SOM). However, by allowing trainable feedback connections, one can obtain
      Markovian maps with superior memory depth and topography preservation. We
      elaborate on the importance of non-Markovian organizations in topographic maps of
      sequential data.

PMID- 16907637
TI  - On the consistency of the blocked neural network estimator in time series
      analysis.
AB  - We describe a nonlinear regression problem, where the regression functions have
      an additive structure and the dependent variable is a one-dimensional time
      series. Multivariate time series with unknown time delay operators are used as
      independent variables. By fitting a feedforward neural network with block
      structure to the data, we estimated the additive regression function and,
      parallel to this, the time lags. We present the consistency proof of neural
      network weights estimator and the time lag estimator independently from each
      other. In the practical part of the article, we present the useful feature of
      blocked neural networks to estimate the relevance measures of each input variable
      in a simple way. Furthermore, we propose an approach to solve the well-known
      variable selection problem for the class of nonlinear multivariate beta-mixing
      time series models considered here. Finally, we apply the methodology to an
      artificial example.

PMID- 16907639
TI  - Toward a comprehensive set of asthma susceptibility genes.
AB  - Epidemiological and twin studies have demonstrated that asthma is under genetic
      and environmental influences. Numerous candidate gene association studies as well
      as genome-wide linkage scans have followed, aiming to elucidate the genetic
      architecture underlying this complex disease. Several promising asthma
      susceptibility genes were identified, and a comprehensive catalogue of these
      genes seems a realistic goal within 5 to 10 years. However, a key challenge is to
      understand the combination of genes and environmental factors that gives rise to
      the disease in a specific individual. Currently, most of the reports of asthma
      susceptibility genes are either preliminary or controversial, with little
      knowledge about the genetic mechanisms leading to abnormal function of the gene
      that promotes the development of asthma. Replications of published associations
      are relatively few. Many factors, including the inherent complexity of asthma as
      well as methodological issues, can explain these inconsistencies. Promising
      genetic tools are emerging with the completion of the International HapMap
      Project that will increase the scope of gene-discovery investigations. It is
      hoped that these tools, combined with validation studies in additional
      populations, will enable the creation of a comprehensive catalogue of
      susceptibility genes for asthma. Notwithstanding the difficulties in making sense
      of the vast amount of new genetic data, we already see the emergence of new
      biological pathways of atopy, airway remodeling, and asthma that may lead to
      novel therapeutic approaches.

PMID- 16907640
TI  - Transplacental transfer of a growth hormone-releasing hormone peptide from mother
      to fetus in the rat.
AB  - Previous studies showed that when growth hormone-releasing hormone (GHRH) was
      administered to either pregnant rats or pigs as a plasmid-mediated therapy,
      pituitary weight, somatotroph and lactotroph numbers, and postnatal growth rate
      of the offspring increased. To determine if these responses resulted from direct
      effects of GHRH on the fetus or were secondary to effects incurred in the mother,
      we studied in the rat the transplacental transfer of a GHRH analog (HV-GHRH) to
      the fetus from the maternal circulation. For the in vivo study, HV-GHRH was
      labeled with 125I and purified by reverse-phase high-performance liquid
      chromatography (HPLC). At 18 days of gestation, pregnant dams were administered a
      priming intravenous dose followed by a constant infusion of the labeled peptide.
      Approximately 2 days later, intact [125I]-HV-GHRH was isolated from the fetal
      liver, stomach contents, and brain. The amounts of tracer were positively
      correlated with those present in the corresponding dam's plasma. These data
      suggest that a GHRH analog of nonplacental origin, even at physiologic
      concentrations, can cross the placenta and, therefore, has the potential to
      influence fetal pituitary development directly.

PMID- 16907641
TI  - A combined DNA vaccine-prime, BCG-boost strategy results in better protection
      against Mycobacterium bovis challenge.
AB  - In this study, we demonstrated that calves vaccinated with a combined DNA vaccine
      encoding Ag85B, MPT- 64, and MPT-83 antigens from the Mycobacterium tuberculosis
      for the priming and subsequently boosting with BCG prior to experimental
      challenge with virulent Mycobacterium bovis (M. bovis) resulted in improved
      immune responses over immunizing. Vaccination with the combined DNA/BCG induced
      higher levels of antigen- specific gamma interferon (IFN-gamma) in whole-blood
      cultures 4 weeks after final vaccination and the level of antigen-specific IFN
      gamma in response to Ag85, MPT-64, and MPT-83 were still higher 4 weeks after
      challenge when compared to the combined DNA group. There was a significant bias
      toward induction of CD4+ T cells rather than CD8+ T cells responses, and the mean
      percentage of CD4+ T cells was increased about 2.6-fold in peripheral blood
      mononuclear cells (PBMC) cultures in DNA prime-BCG boost vaccination when
      compared to the nonvaccinated group. In addition, DNA prime-BCG boost vaccination
      resulted in stronger humoral immune responses, and the levels of the specific
      antibodies to three antigens were increased two- to 32- fold when compared to the
      combined DNA group. Vaccination with the combined DNA/BCG induced a high level of
      protection against an intratracheal challenge with virulent M. bovis, based on a
      significant enhancement of six pathological and microbiological parameters of
      protection compared to the nonvaccinated group. Finally, the combined DNA/BCG
      increased the protective efficacy by more than 10-100-fold as measured by reduced
      CFU counts in the lungs from calves challenged with M. bovis compared to the
      combined DNA and BCG groups. These results suggest that use of the prime-boost
      strategy offers better protection against bovine tuberculosis than does the
      combined DNA vaccines and BCG.

PMID- 16907642
TI  - Characterization of mouse serum tenascin-X.
AB  - The interstitial extracellular matrix tenascin-X (iTNX), which has a molecular
      mass of roughly 450 kDa, is expressed at high levels in muscular tissues and
      skin. In this study, we identified the serum form of TNX (sTNX) with a molecular
      mass of 200 kDa in the mouse. Western blot analysis with specific antibodies
      against fibronectin type III-like (FNIII) repeats of TNX and N-terminal sequence
      analysis of 200-kDa sTNX revealed that the N-terminus of sTNX is located in the
      juncture between the 16th FNIII (M16) and 17th FNIII (M17) repeats of iTNX. The
      200-kDa sTNX contains 15 FNIII repeats and a fibrinogen domain identical to the
      Cterminal portion of the iTNX. TNX-deficient mice lacked not only iTNX but also
      sTNX. Furthermore, 200-kDa sTNX was generated by cleavage of the spleen iTNX by
      spleen homogenate, and its generation was inhibited by protease inhibitors. These
      results suggest that sTNX is generated by proteolytic cleavage of iTNX.

PMID- 16907643
TI  - Lark is the splicing factor RBM4 and exhibits unique subnuclear localization
      properties.
AB  - Lark is an RNA-binding protein of the RNA recognition motif (RRM) class and, in
      Drosophila, Lark is required for embryonic development. In attempting to
      determine the function of human Lark we uncovered a frame-shift error in the
      published sequence to reveal that Lark is, in fact, RBM4, a recently described
      splicing regulator. We then went on to show that RBM4 localizes in nuclear
      speckles and nucleoli, supporting its potential role in splicing or RNA
      processing. Immunofluorescence imaging of full-length and mutated RBM4 revealed
      that the C-terminus of RBM4 is crucial for targeting to speckles. Unlike many
      other splicing factors, however, RBM4 does not contain an RS-domain or any other
      known targeting site. RBM4 redistributed to perinucleolar clusters upon the
      addition of a transcription inhibitor, whereas other splicing factors display
      increased localization to speckles in the absence of transcription. This finding
      is consistent with the potential existence of a novel subnuclear targeting
      pathway. In conclusion, RBM4 and Lark are the same protein, are localized in
      speckles and nucleoli, but can redistribute to perinucleolar clusters, consistent
      with a novel subnuclear pathway.

PMID- 16907644
TI  - Murine ortholog of the novel glycosyltransferase, B3GTL: primary structure,
      characterization of the gene and transcripts, and expression in tissues.
AB  - Glycosylation of proteins and lipids is important in cellular communication and
      maintenance of tissues. B3GTL (beta3-glycosyltransferase-like) is a novel
      glycosyltransferase that is found in multicellular animals ranging from mammals
      to insects and nematodes. The aim of this work was to identify and characterize
      the B3GTL gene in the mouse and to study its expression in various tissues. The
      murine gene codes for a protein which shares 84% amino acid sequence identity
      with its human ortholog, and contains all the primary structural features that
      characterize B3GTL proteins. The murine and human B3GTL genes share an identical
      exon/intron organization, and both genes utilize multiple polyadenylation
      signals. Their promoter regions show extensive conservation, implying that the
      two genes also share regulatory similarities. This notion was reinforced by
      Northern hybridization analysis of mouse tissues, which showed the tissue
      distribution of B3GTL mRNA to be similar to that previously found in human
      tissues, with the heart, kidney, and brain being major sites of expression in
      both species. The localization of B3GTL mRNA was studied by in situ hybridization
      in an extensive collection of mouse tissues, of which the granular cells of the
      olfactory bulb and the epithelium of the seminal vesicle displayed particularly
      strong signals. Together, these analyses indicate that the B3GTL mRNA is subject
      to strong tissue-specific and developmental regulation. The findings reported
      here make possible the design of a B3GTL "knock-out" mouse, provide a framework
      for analyzing the regulation of the gene, and provide an extensive catalog of
      tissues in which this novel protein acts.

PMID- 16907645
TI  - Estrogen directly attenuates human osteoclastogenesis, but has no effect on
      resorption by mature osteoclasts.
AB  - Estrogen deficiency arising with the menopause promotes marked acceleration of
      bone resorption, which can be restored by hormone replacement therapy. The
      inhibitory effects of estrogen seem to involve indirect cytokine- mediated
      effects via supporting bone marrow cells, but direct estrogen-receptor mediated
      effects on the bone-resorbing osteoclasts have also been proposed. Little
      information is available on whether estrogens modulate human osteoclastogenesis
      or merely inhibit the functional activity of osteoclasts. To clarify whether
      estrogens directly modulate osteoclastic activities human CD14+ monocytes were
      cultured in the presence of M-CSF and RANKL to induce osteoclast differentiation.
      Addition of 0.1-10 nM 17beta-estradiol to differentiating osteoclasts resulted in
      a dose-dependent reduction in tartrate resistant acid phosphatase (TRACP)
      activity reaching 60% at 0.1 nM. In addition, 17beta-estradiol inhibited bone
      resorption, as measured by the release of the C-terminal crosslinked telopeptide
      (CTX), by 60% at 0.1 nM, but had no effect on the overall cell viability. In
      contrast to the results obtained with differentiating osteoclasts, addition of
      17beta-estradiol (0.001-10 nM) to mature osteoclasts did not affect bone
      resorption or TRACP activity. We investigated expression of the estrogen
      receptors, using immunocytochemistry and Western blotting. We found that ER-alpha
      is expressed in osteoclast precursors, whereas ER- beta is expressed at all
      stages, indicating that the inhibitory effect of estrogen on osteoclastogenesis
      is mediated by ER-alpha for the major part. In conclusion, these results suggest
      that the in vivo effects of estrogen are mediated by reduction of
      osteoclastogenesis rather than direct inhibition of the resorptive activity of
      mature osteoclasts.

PMID- 16907646
TI  - No association of DNA ligase-I polymorphism with the risk of lung cancer in north
      Indian population.
AB  - DNA ligases play an essential role in repair, replication, and recombination of
      DNA, and catalyzes the formation of a phosphodiester bond at a nick junction on
      single- and double-strand breaks. We have conducted a hospital-based case-control
      study to examine the role of polymorphism of DNA repair gene ligase I (LIGI) in
      the context of lung cancer risk for north Indian population. One hundred, fifty
      one primary lung cancer cases and an equal number of matching hospital controls
      were collected. The LIGI polymorphism was determined by using the PCR-RFLP
      method. The association between polymorphisms in the LIGI gene with the risk of
      lung cancer was estimated by computing odds ratios (ORs) and a 95% confidence
      interval (CI) using a Multivariate Logistic Regression Analysis. The risk for
      lung cancer was not associated for individuals featuring LIGI (AC) (OR -0.8, 95%
      CI = 0.44-1.40) and (AA) (OR -0.8, 95% CI = 0.41-1.80) genotypes. The DNA repair
      gene (LIGI) may not be playing an important role in modulating the risk of lung
      cancer in the north Indian population.

PMID- 16907647
TI  - Antithrombotic treatment in atrial fibrillation.

PMID- 16907648
TI  - Statins and breast cancer: a smoking gun or guilt by association?
AB  - Statins are widely prescribed, effective cholesterol-lowering drugs. Indeed,
      atorvastatin and simvastatin were the most commonly prescribed drugs in the US in
      2004, with > 70 million prescriptions written for atorvastatin alone. Statins are
      pleiotropic agents and, after an early study of patients with coronary heart
      disease showed a lower than expected incidence of cancers, preclinical studies
      were carried out that have supported the potential anticancer activity of these
      compounds. However, clinical reports on the relationship between statin use and
      breast cancer risk have yielded mixed results, with no association and both
      positive and negative associations being observed. Because breast cancer is the
      most frequent cancer in women, any link between statin use and breast cancer risk
      would have major public health implications. The current evidence suggests that
      statins are safe and effective agents in treating hyperlipidaemia and no evidence
      of increase or decrease risk of breast cancer. Indeed, more research is needed to
      define whether long-term statin therapy may decrease or increase the risk of
      breast cancer.

PMID- 16907649
TI  - Safety of neuraminidase inhibitors for influenza.
AB  - Neuraminidase inhibitors, oseltamivir and zanamivir, are used for the treatment
      of, and protection from, influenza. The safety of these compounds has been
      assessed in systematic reviews. However, the data presented are somewhat limited
      by the paucity of good quality adverse event data available. The majority of
      safety outcomes are based on evidence from just one or two randomised controlled
      trials. The results of the systematic reviews suggest that neuraminidase
      inhibitors have a reasonable side effect and adverse effect profile if they are
      to be used to treat or protect patients against a life-threatening disease.
      However, if these compounds are to be prescribed in situations in which avoidance
      of inconvenience or minor discomfort is hoped for, then the balance of harms to
      benefits will be more difficult to judge.

PMID- 16907650
TI  - The withdrawal of antiepileptic drugs in patients with non-epileptic seizures:
      safety considerations.
AB  - The majority of patients with psychogenic non-epileptic seizures (PNES) do not
      have epilepsy. There are a number of compelling reasons to take these patients
      off antiepileptic drugs (AEDs), including drug toxicity and teratogenicity, as
      well as possibly poorer outcome of PNES and increased risk of iatrogenic harm
      when patients present to emergency rooms on AEDs as emergencies. However, many
      patients with PNES who do not have epilepsy remain on AEDs postdiagnosis. Some
      studies do report patients taken off medication as an outcome measure, but with
      no assessment of the safety of withdrawal, or specification of the criteria for
      'excluding' epilepsy. One study has assessed the safety of taking patients
      satisfying some simple criteria for the absence of an underlying epilepsy off
      AEDs, and has found the procedure to be safe, given appropriate postwithdrawal
      follow-up. Patients with PNES who do not have evidence of epilepsy should be
      referred to a centre with appropriate expertise in epilepsy diagnosis so that
      AEDs can be withdrawn in safe conditions.

PMID- 16907651
TI  - Update on ethambutol optic neuropathy.
AB  - Ethambutol optic neuropathy is a well-recognised adverse ocular event in patients
      who receive ethambutol for the treatment of mycobacterial infections. Much has
      been published on this condition; however, understanding of patient outcomes and
      the mechanism by which ethambutol optic neuropathy occurs, as well as data
      published in textbooks and reference books, tend to lag behind what is currently
      known. The purpose of this article is to update the clinician on what is
      currently accepted in regards to the clinical presentation of ethambutol optic
      neuropathy and what type of eye care should be provided to patients treated with
      this medication. In addition, new treatment recommendations are suggested to
      assist clinicians in complying with currently accepted standards of care.

PMID- 16907652
TI  - Cardiac dysfunction associated with trastuzumab.
AB  - The HER2/neu gene is amplified in approximately 25% of breast cancers, leading to
      HER2 protein overexpression and shortened overall survival and time to relapse.
      Trastuzumab is a humanised, monoclonal antibody against HER2, which improves
      survival for women with metastatic HER2-overexpressing breast cancer and reduces
      the risk of recurrence in women with early stage HER2-overexpressing breast
      cancer. Cardiac toxicity was an unexpected finding in the pivotal Phase III trial
      leading to the approval of trastuzumab, and prospective cardiac monitoring has,
      therefore, been incorporated into more recent clinical trials of trastuzumab.
      This article reviews the cardiac toxicity findings in key trastuzumab clinical
      trials and clinical characteristics of trastuzumab-associated cardiac toxicity.

PMID- 16907653
TI  - Potential side effects of renin inhibitors--mechanisms based on comparison with
      other renin-angiotensin blockers.
AB  - Angiotensin (Ang) II plays important roles in the development of hypertension and
      cardiovascular and renal injury. Pharmaceutical approaches to block its activity
      led to the development of angiotensin-converting enzyme inhibitors and
      angiotensin receptor blockers. Numerous trials have documented their efficacy in
      controlling blood pressure, minimising left ventricular remodelling, preventing
      progression to heart failure, ameliorating proteinuria and retarding renal
      disease progression. Although they are considered safe in general, there remain
      concerns about the potential for adverse events in certain target populations.
      Recently, several novel, low molecular weight renin inhibitors without the
      extended peptide-like backbone of previous renin inhibitors were developed with
      favourable pharmacokinetic properties. They have been shown to successfully
      reduce Ang II levels in normal volunteers and to lower blood pressure in patients
      with mild-to-moderate hypertension. In this review, the authors summarise current
      knowledge about these renin inhibitors.

PMID- 16907654
TI  - Angiotensin-converting enzyme inhibitor-related angioedema: how to deal with it.
AB  - Angiotensin-converting enzyme inhibitor-related angioedema is a well documented
      condition, which seems to occur in up to 1% of treated patients. It represents a
      problem for both the clinician and the patient: for the clinician, the diagnosis
      may be difficult due to its peculiar clinical characteristics, whereas for the
      misdiagnosed patient the delay prolongs a potentially dangerous situation. If the
      drug is not discontinued, the attacks tend to become worse and even life
      threatening. There are now evidences that increased levels of bradykinin have an
      important role in the pathophysiology of attacks and, moreover, there are genetic
      factors that render certain individuals susceptible to angiotensin-converting
      enzyme inhibitor-related angioedema. In this review, the authors analyse the
      pathogenetic mechanism, the clinical presentation, the management and future
      perspectives of research on this condition.

PMID- 16907655
TI  - Statins and myotoxicity: a therapeutic limitation.
AB  - Hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors represent the
      most successful class of drugs for the treatment of hypercholesterolaemia and
      dyslipidaemia implicated in the pathogenesis of coronary heart disease and
      atherosclerosis. However, the popular profile of statins in terms of efficacy has
      been maligned by its adverse events. The myotoxicity, ranging from mild myopathy
      to serious rhabdomyolysis, associated with HMG-CoA reductase inhibitors, during
      treatment of hypercholesterolaemia is of paramount importance. Rhabdomyolysis is
      a rare but idiosyncratic muscle wasting disorder of different etiologies. Statin
      associated rhabdomyolysis causes skeletal muscle injury by self-perpetuating
      events leading to fatal irreversible renal damage through a series of biochemical
      reactions. Preferential distribution and action of statins in liver could be the
      key to minimise myotoxicity concerns. Hepato-specific distribution of statins is
      governed by various factors such as physicochemical properties, pharmacokinetic
      properties and selective transporter-mediated uptake in liver rather in
      extrahepatic cells. The interactions of statins with concomitant drugs of
      different classes merit attention for their safety profile. Although
      pharmacokinetic as well as pharmacodynamic interactions have been implicated in
      pathophysiology of statin-induced muscle wasting, the underlying mechanism is not
      clearly understood. Besides, pharmacokinetic and phramcodynamic factors, statin
      associated myotoxcity may also implicate pharmacogenomic factors. The
      pharmacogenomics characterised by CYP polymorphism and other genetic factors is
      responsible for inter-individual variations to efficacy and tolerability of
      statins. The pathophysiological mechanisms may include statin-induced differences
      in cholesterol:phospholipid ratio, isoprenoid levels, small GTP binding proteins
      and apoptosis. However, the present understanding of pathophysiological
      mechanisms, does not offer a reliable approach to address the same at preclinical
      level. Although statin-associated myotoxicity affects compliance, quality of life
      of patient and discontinuation rate, yet the low incidence of myotoxicty
      including rhabdomyolysis and less severity of commonly occurring myopathy and
      myalgia do not raise doubts about the clinical efficacy and tolerability of
      statins. Medical management of myotoxicity seems to be pivotal for the proper
      compliance of patients with statin treatment. The appropriate and judicious use
      of drugs would substantially reduce the likelihood of developing clinically
      important myopathy.

PMID- 16907656
TI  - Side effects of using nitrates to treat angina.
AB  - Nitrates are very effective antianginal and anti-ischaemic agents. Provision of a
      long nitrate-free interval or low plasma nitrate levels prior to the morning dose
      prevents the loss of clinical efficacy by preventing the development of
      tolerance. However, side effects during nitrate therapy are common. Headache is
      the most common side effect of nitrates; often dose-related and reported by up to
      82% of patients in placebo-controlled trials. Nearly 10% of patients are unable
      to tolerate nitrates due to disabling headaches or dizziness. In others,
      headaches are mild-to-moderate in severity and either resolve or diminish in
      intensity with continued nitrate therapy. Nitrate-induced hypotension is common,
      but often asymptomatic. In rare instances, nitrate-induced hypotension is severe
      and accompanied by marked slowing of the heart rate and syncope. Use of nitrates
      in patients who experience syncope after administration of nitrates is
      contraindicated. Nitrates rarely cause coronary steal and myocardial ischaemia.
      Nitrate rebound may occur and patients may experience nocturnal anginal episodes
      during intermittent therapy with nitroglycerin patches. Administration of
      nitrates is contraindicated with concomitant use of phosphodiesterase-5
      inhibitors used for the treatment of erectile dysfunction, as combination therapy
      may lead to profound hypotension and even death. There are disturbing
      observational reports in the literature that continuous, prolonged use of
      nitrates may lead to increased mortality and recurrent myocardial infarctions.
      Large, randomised, placebo-controlled studies are needed to confirm or refute
      these reports; until then, the use of nitrates to treat angina is here to stay.

PMID- 16907657
TI  - The safety of phosphate binders.
AB  - Disturbances of mineral metabolism occur during the early stages of chronic
      kidney disease. As renal function worsens, excess dietary phosphorus accumulates
      and blood levels increase, that can be clearly seen when the glomerular
      filtration rate has fallen below 30 ml/min/1.73 m2. In patients with end stage
      renal disease, standard dialysis (three times/week) falls far short of removing
      adequate amounts of absorbed phosphorus; therefore, hyperphosphataemia is found
      in the majority of these patients. Hyperphosphataemia has long been associated
      with progression of secondary hyperparathyroidism and renal osteodystrophy, it
      can also lead to soft-tissue and vascular calcification. Recent observational
      data have associated hyperphosphataemia with increased cardiovascular mortality
      among dialysis patients. Adequate control of serum phosphorus remains a
      cornerstone in the clinical management and, despite the growing amount of
      available therapeutic options, achievement of NFK/KDOQI targets for mineral
      metabolism remain poor. Several reasons may explain the failure to adequately
      treat hyperphosphataemia: poor compliance with diet and phosphate binder
      prescriptions are common causes. Also, factors related with cost, tolerance,
      palatability, safety and efficacy are important. In this article, the authors
      review the advantages and drawbacks of conventional and emerging therapies in
      phosphorous binding.

PMID- 16907658
TI  - Hypersensitivity reactions associated with oxaliplatin.
AB  - The reported incidence of hypersensitivity reactions (HSRs) associated with
      oxaliplatin in patients with colorectal cancer (CRC) is approximately 12%, with 1
      - 2% of patients developing grade 3 or 4 in severity. However, the recent rising
      incidence of HSR to oxaliplatin observed is the result of increasing clinical
      use. HSR to oxaliplatin may manifest as facial flushing, rash/hives, tachycardia,
      dyspnoea, erythema, pruritus, fever, tongue swelling, headache, chills, weakness,
      vomiting, burning sensations, dizziness and oedema. Anaphylactic shock is rare
      but serious, and must be considered in the event of hypotension. No definitive
      approaches to prevent and treat HSR associated with oxaliplatin are available;
      however, few successful strategies have been reported. Such strategies include:
      slowing the infusion rate, use of steroids and antagonists of type 1 and 2
      histamine receptors, and desensitisation. Successful implementation of
      oxaliplatin desensitisation protocols based on other platinum-containing
      compounds have been reported, which could enable a small number of patients who
      experience severe HSR to further receive an effective therapy for CRC. However,
      reintroductions have only been reported as single case studies or small cohorts.
      Large-scale validation on desensitisation strategies are still missing. Recently,
      subcutaneous adrenaline has also been utilised as an alternative approach to
      manage HSR to oxaliplatin. Knowledge of this rare but real toxicity of
      oxaliplatin is paramount because the use of this drug continues to increase not
      only for the treatment of patients with stage II-IV CRC, but also other solid
      malignancies. In this article, the author discusses the incidence, clinical
      presentation, pathogenesis, risk factors and current strategies of management of
      HSR associated with oxaliplatin.

PMID- 16907660
TI  - Off-label and unlicensed prescribing for newborns and children in different
      settings: a review of the literature and a consideration about drug safety.
AB  - This review aims to give an updated overview of the worldwide situation of off
      label and unlicensed drug use in the paediatric field, also taking into account
      the safety of this kind of treatment. A Medline and Embase search was performed
      between 1990 and 2006 and a total of 52 studies were identified and included in
      the systematic review. From the authors' analysis of the literature, the extent
      of paediatric unlicensed/off label use is higher in neonatal and paediatric
      intensive care units and oncology wards, compared with primary care. Moreover,
      among the nine studies reporting the contribution of an off-label/unlicensed drug
      use to the occurrence of adverse events, the percentage of unlicensed and/or off
      label prescriptions involved in an adverse drug reaction ranged between 23 and
      60%. To ensure that children are not exposed to unnecessary risks, controlled
      clinical trials are required. In addition, future research should be directed
      towards the identification of individual drugs that cause serious adverse drug
      reactions and lack product information.

PMID- 16907659
TI  - The safety of veralipride.
AB  - The perimenopausal period, from 1 to 4 years, is characterised by vasomotor
      symptoms, or hot flushes, and other effects due a deficit of estrogens.
      Approximately 85% of women have hot flushes for 1 year and 25 - 50% continue for
      up to 5 years. The cause of hot flushes has been linked to dysfunction of the
      thermoregulatory centre caused by estrogen withdrawal. One proposal for the
      aetiology of hot flushes is that the thermoregulatory zone is shifted downward in
      patients who experience hot flushes. Estrogen withdrawal creates a change of the
      central opioid system and a thermoregulatory instability. Estrogen and/or
      progestin replacement is the treatment of choice for this distressing symptom.
      However, steroid replacement may be associated with risks and complications, and
      is limited in some subjects by well-known contraindications. Veralipride, a
      synthetic benzamide derivative with antidopaminergic action, is effective in
      reducing the frequency and severity of hot flushes associated with menopausal
      hypoestrogenism, gaining interest as a non-hormonal treatment for climacteric
      flushing. In recent years, extrapyramidal disorders associated with veralipride
      therapy have been reported and are often due to drug misuse. Adverse effects
      include acute dyskinesia or Parkinsonism, which may occur after many months of
      treatment. An association between adverse effects and mistake of administration
      has been described. This article discusses available data on the benefits and
      risks of veralipride therapy for menopausal symptoms.

PMID- 16907661
TI  - An evidence-based systematic review of herb and supplement interactions by the
      Natural Standard Research Collaboration.
AB  - Reported utilisation of prescription drug use concurrently with herbal or vitamin
      products have increased, placing an estimated 15 million patients at risk of
      potential drug-supplement interactions. This systematic review aims to
      consolidate relevant herb and supplement interactions data available for some of
      the more common classes of interactions experienced by clinicians. These classes
      include: hypoglycaemic/hyperglycaemics; hypotensive/hypertensives, diuretics,
      sedatives, cardiac glycosides, monoamine oxidase inhibitors, selective serotonin
      reuptake inhibitors, laxatives, immunomodulators, agents that may increase the
      risk of bleeding or clotting, agents that may be hepatotoxic, agents that may
      have hormonal properties, and agents with cytochrome P450 enzyme activity. The
      format is designed to promote use as a decision support tool for healthcare
      providers.

PMID- 16907662
TI  - The 2nd International Drug Hypersensitivity Meeting 18 - 21 April 2006, The
      University of Liverpool, Liverpool, UK.
AB  - The 2nd International Drug Hypersensitivity Meeting was held at Liverpool, UK on
      18 - 21 April, 2006. This meeting, attended by almost 200 delegates with
      expertises in chemistry, pharmacology, toxicology, allergy and immunology,
      provided an excellent environment to discuss recent advances in the understanding
      of the chemical, cellular, molecular and genetic basis of drug hypersensitivity.
      Furthermore, specific symposia addressed clinical, industrial and regulatory
      perspectives of drug hypersensitivity reactions. The ultimate aim of the meeting
      was to contribute towards a better understanding and management of this
      particular form of serious adverse drug reaction. The authors herein provide a
      synopsis of the main research and clinical findings discussed at the meeting.

PMID- 16907663
TI  - Integrin signalling in directed cell migration.
AB  - Migrating cells tend to continue moving in the same direction, a property called
      persistence. During migration, cells, by definition, form new adhesions at their
      front and break old adhesions at the rear. We hypothesize that the distinction
      between new adhesions at the front and older adhesions at the rear plays a major
      role in directional persistence. We propose specific mechanisms of persistence on
      the basis of known properties of integrin signals, in hope of stimulating
      investigation of these ideas.

PMID- 16907664
TI  - Positioning centrosomes and spindle poles: looking at the periphery to find the
      centre.
AB  - Centrosome positioning is tightly controlled throughout the cell cycle and
      probably shares common regulatory mechanisms with spindle-pole positioning. In
      this article, we detail the possible mechanisms controlling centrosome and
      spindle positioning in various organisms both in interphase and mitotic cells,
      and discuss recent findings showing how microtubule plus-end-associated proteins
      interact with the cell cortex. We suggest that microtubule plus-end complexes
      simultaneously regulate microtubule dynamics and microtubule anchoring at the
      cell periphery to allow proper centrosome and spindle-pole positioning.

PMID- 16907665
TI  - Which is more important to the initiation of contact lens related microbial
      keratitis, trauma to the ocular surface or bacterial pathogenic factors?

PMID- 16907666
TI  - Rethinking contact lens associated keratitis.
AB  - This review presents a critical analysis of the literature relating to the use of
      binomial and polynomial classification schemes for categorising corneal
      infiltrative events (CIEs) associated with contact lens wear and the epidemiology
      of such events. The results of the Manchester Keratitis Study-a 12-month,
      prospective, hospital-based epidemiological study of contact lens wearer
      suffering from CIEs-are used as a tool to challenge and test traditional thinking
      in relation to contact lens associated keratitis. An innovative aspect of this
      study is the use of a novel clinical severity matrix to systematically score the
      severity of CIEs based on 10 key signs and symptoms. The ambiguities inherent in
      using binomial classification schemes (such as, microbial versus sterile,
      ulcerative versus non-ulcerative etcetera) are highlighted. The failure of a
      polynomial scheme-due to extensive classification overlap between proposed sub
      types of CIEs-is demonstrated using a Venn diagram. A cartographic analysis
      reveals that infiltrates tend to occur in the superior cornea of patients wearing
      extended wear silicone hydrogel lenses, in the central cornea of patients wearing
      daily wear hydrogel daily disposable lenses and in the peripheral cornea of
      patients wearing daily wear hydrogel (excluding daily disposable) lenses.
      Infiltrates that occur more towards the limbus are less severe. The incidence of
      CIEs is higher when contact lenses are worn overnight. Logistic analysis reveals
      that the risk of developing a severe CIE is five times greater with conventional
      hydrogel extended wear versus silicone hydrogel extended wear. The male gender,
      smoking, a healthy eye and body, and the late Winter months are associated with
      an increased risk of developing CIEs. The rate of significant visual loss as a
      result of developing a CIE is low. Two key conclusions are drawn from this work,
      which represent a radical rethinking of this potentially sight-threatening
      condition. CIEs should be considered as a continuous spectrum of ocular disease.
      If a contact lens wearer presents with a sore eye that is becoming progressively
      worse and a CIE is observed in that eye, lens wear should be suspended and anti
      microbial therapy initiated immediately.

PMID- 16907668
TI  - Cup-to-disc ratios of Aboriginal and non-Aboriginal youths.
AB  - BACKGROUND: The determination of the cup-to-disc ratio (C/D) is a standard
      procedure in an eye examination and is pivotal in the diagnosis of glaucoma.
      Determining the size of the C/D ratios of different races of young people may be
      helpful in determining the genetically predetermined differences between
      Aboriginal and non-Aboriginal people. The aim of this study was to determine
      whether there is a statistically significant difference in the average C/D ratios
      of young Aboriginal and non-Aboriginal people. METHODS: The overall average C/D
      ratios of 104 subjects aged between five and 23 years were compared for two age
      matched groups by stereoscopic indirect ophthalmoscopy. Differences between the
      overall average C/D ratios of the two groups were assessed for significance using
      an unpaired Student's t test. RESULTS: While the range of C/D ratios within each
      group was the same (zero to 0.7), there was a statistical difference (p < 0.001)
      between the overall average C/D ratios of the Aboriginal (C/D = 0.295) and non
      Aboriginal (C/D = 0.159) groups. CONCLUSIONS: Results indicating a difference
      between the overall average C/D ratios between Aboriginal and non-Aboriginal
      young people may have implications for initial assessments of glaucoma in
      patients of any age.

PMID- 16907667
TI  - An automated microaneurysm detector as a tool for identification of diabetic
      retinopathy in rural optometric practice.
AB  - BACKGROUND: With the increase in the prevalence of diabetes, rural optometric
      clinics stand to increase their patient load and assessment of diabetic eye
      disease. This study aimed to assess whether automated identification of diabetic
      retinopathy based on the presence of microaneurysms is an effective tool in
      clinical practice. METHODS: We analysed 758 fundal images of 385 patients with
      diabetes attending the clinic obtained using a Canon CR5 with an EOS10 digital
      camera through a dilated pupil. Five optometrists employed in the clinic assessed
      the diabetic retinopathy using binocular indirect ophthalmoscopy. The sensitivity
      and specificity of the automated system used to analyse the retinal fundal images
      was determined by comparison with optometric and ophthalmologic assessment.
      RESULTS: The optometrists achieved 97 per cent sensitivity at 88 per cent
      specificity with respect to the ophthalmic classification for detecting
      retinopathy. CONCLUSION: The automated retinopathy detector achieved 85 per cent
      sensitivity at 90 per cent specificity at detecting retinopathy. The automated
      microaneurysm detector has a lower sensitivity compared to the optometrists but
      meets NHMRC guidelines. It may impact on the efficiency of rural optometric
      practices by early identification of diabetic retinopathy. Automated assessment
      can save time and be cost-effective, and provide a history of changes in the
      retinal fundus and the opportunity for instant patient education using the
      digital images.

PMID- 16907669
TI  - Assessment of the accuracy and reliability of the Topcon CT80 non-contact
      tonometer.
AB  - BACKGROUND: The reliability of non-contact tonometers has been reported
      extensively in the literature. This study was designed to assess reliability of
      the new Topcon CT80 non-contact tonometer in normotensive subjects, using the
      Goldmann tonometer as the standard. METHODS: The accuracy of the Topcon CT 80 non
      contact tonometer was assessed by comparing its IOP assessments with those of the
      Goldmann applanation tonometer, on 60 right eyes of young healthy subjects with
      normal intraocular pressures. Each subject's intraocular pressure was assessed
      with each technique on two separate occasions, one week apart. The reliability of
      each technique was determined by the assessment of its inter-session
      repeatability using the Bland-Altman method. The 95 per cent limits of agreement
      for the two methods were also determined. RESULTS: No statistically significant
      difference was found between the average intraocular pressures measured with the
      two techniques (p > 0.05). The inter-session repeatability indices for the two
      techniques did not differ significantly (p > 0.05). The mean difference in
      intraocular measurements between the two techniques was 0.2 +/- 1.5 mmHg (mean +/
      SD) and the 95 per cent limits of agreement were -3.14 and +2.74 mmHg, with the
      non-contact tonometer returning higher readings than the Goldmann tonometer.
      CONCLUSION: In this sample of normotensive subjects, the Topcon CT80 non-contact
      tonometer proved to be accurate and as reliable as the Goldmann tonometer in the
      assessment of intraocular pressure. Thus, it can be used as an objective clinical
      method for the assessment of normal intraocular pressure.

PMID- 16907670
TI  - The possible effect of undercorrection on myopic progression in children.
AB  - BACKGROUND: Undercorrection has recently been found to enhance the rate of
      progression of myopia. This result was thought to be controversial as it
      contrasted with expectations based on animal studies, as well as the results
      found wearing progressive addition lenses. The aim of the present study was to
      again determine the effect of undercorrection on the progression of myopia in a
      random population of children who are known to be very susceptible to myopia.
      METHODS: A cohort of 48 myopic children, aged six to 15 years was randomly
      assigned to either a fully corrected group (n = 23) or to an undercorrected group
      (n = 25). The subjects in the latter group were blurred by +0.50 D. The
      prospective study extended over a period of 18 months. Optometric examinations
      were carried out at the beginning of the study, then at six-month, 12-month and
      18-month follow-up. RESULTS: Undercorrection produced a slight but not
      statistically significant increase in myopic progression over the 18-month period
      equal to 0.17 D, compared to full correction. A similar trend towards an increase
      in progression was noted in females and in children with near esophoria.
      CONCLUSION: This study supports the evidence that undercorrection does not
      represent an effective therapy to slow the rate of early-onset myopic
      progression, regardless of near heterophoria.

PMID- 16907671
TI  - An unusual case of an extra row of eyelashes in the superior eyelid skin crease.
AB  - A diabetic patient was referred to the office for assessment of anterior
      blepharitis and associated tear film complications. On examination, he was noted
      to have bilateral, symmetrical rows of extra cilia within both upper eyelid skin
      creases. Differential diagnoses of aberrant cilia are discussed.

PMID- 16907672
TI  - Diagnosis and management of accommodative esotropia.
AB  - BACKGROUND: Accommodative esotropia is the most common form of childhood
      strabismus presenting to optometric practice. Functional and cosmetic outcomes
      are often excellent but depend on accurate diagnosis, urgent and correct initial
      management and careful follow-up. CASE REPORTS: We present several cases that
      highlight important aspects of the clinical care of accommodative esotropia. The
      first patient was mismanaged by undercorrection of hypermetropia, but was later
      accurately diagnosed to have accommodative esotropia and was subsequently managed
      successfully with full hypermetropic correction alone. The second patient had an
      accommodative esotropia with amblyopia. The third patient used a near addition to
      correct a residual near esotropia. CONCLUSIONS: The published evidence and these
      cases make several points regarding assessment, diagnosis and management of
      esotropia. Assessment must aim to reach a diagnosis based on aetiology, as the
      aetiology of esotropia has a significant impact on management decisions and
      prognosis.

PMID- 16907673
TI  - Uncertainty of clinical measurements.

PMID- 16907679
TI  - Continuing the evidence-based health care debate in 2006. The progress and price
      of EBM.

PMID- 16907680
TI  - Taking stock of evidence-based medicine: opportunities for its continuing
      evolution.
AB  - Tough but constructive criticisms of evidence-based medicine (EBM) have without
      doubt informed the evolution and serial reconstitutions of this approach to
      clinical decision making and behaviour. Yet, concerns about EBM persist and as
      EBM changes in response to reflection and criticism, so too do the criticisms
      themselves. This paper describes our current understanding of EBM and, to
      identify opportunities for the continuing evolution of EBM, discusses some key
      attributes of EBM that still or now cause us concern. Specifically, these
      attributes are the nature of evidence in EBM; the unknown effectiveness of EBM;
      the clinician-centric focus of EBM; and the potential of EBM to harm patients.

PMID- 16907681
TI  - Can academic and clinical journals be in financial conflict of interest
      situations? The case of evidence-based incorporated.
AB  - The hypothesis is advanced that scholarly journals can find themselves in
      conflict of interest positions when they operate business strategies which for
      commercial reasons may militate against the publication of articles which
      question the usefulness of the products being sold. It is suggested on the basis
      of probabilistic reasoning that the more extensive the merchandizing and the
      greater the commercial profits, the greater is the potential for conflict of
      interest. The alternative hypothesis is advanced that such a conflict of interest
      position cannot possibly exist. The current Hypothesis paper is published in
      order to stimulate debate on the subject of study. The reader is referred to the
      Editor's Note p. 395.

PMID- 16907682
TI  - The hard art of soft science: Evidence-Based Medicine, Reasoned Medicine or both?
AB  - In the past 14 years, Evidence-Based Medicine (EBM) has enjoyed unprecedented
      developments and gained widespread acceptance among health professionals.
      However, should we be content with producing, critically appraising and using the
      best evidence available for our understanding of health problems and decision
      making about them? Are our convictions about EBM's relevance, our conviction and
      intellectual satisfaction with its mastery and adoption enough? Should we
      continue pushing forward along this promising path, or should we further
      diversify the content and scope of EBM? Is EBM the only way to view medicine in
      the near future? This paper presents some options to choose from in terms of
      direction and content as well as questions to answer given the current EBM
      crossroads. More intensive and extensive EBM combined with 'other features'-based
      medicines may be the preferred strategy to follow in the future to determine the
      development, use and evaluation of EBM. Argument-based medicine or Reasoned
      Medicine is one of the options that can be integrated into the mainstream of
      medical reasoning and decision making.

PMID- 16907683
TI  - Evidence-Based Medicine, Reasoned Medicine or both? Commentary on Jenicek, M.
      (2006) 'The hard art of soft science'.

PMID- 16907684
TI  - Blinded by 'science': commentary on Jenicek, M. (2006) 'The hard art of soft
      science'.

PMID- 16907685
TI  - Opportunities to elaborate on casuistry in clinical decision making. Commentary
      on Tonelli (2006). Integrating evidence into clinical practice: an alternative to
      evidence-based approaches.

PMID- 16907686
TI  - EBM for the future.
AB  - A viewpoint on Evidence-Based Medicine from a clinician previously unaware of the
      degree of controversy that appears to exist surrounding the subject is presented
      together with an attempt to provide a fresh approach for the future.

PMID- 16907687
TI  - Beyond 'faith-based medicine' and EBM.
AB  - RATIONALE, AIMS AND OBJECTIVES: Longstanding debate on evidence-based medicine
      (EBM) may have reached a critical saturation point. I briefly report on
      systematic reviews on the recurring themes in the critical literature. In this
      context, some criticisms to EBM are substantial and enduring, although convincing
      arguments to contrast unresolved issues have yet to be produced. Nonetheless, few
      changes have been adopted and conservative attitudes persist in EBM. Despite its
      'success', implementation in practice has been inexorably overshadowed leading to
      paradoxical shortcomings. This controversial scenario offers a formidable
      occasion to gain needed insight. The aim of this paper is to attempt a
      comprehensive analysis by reframing a number of key concerns, while furnishing
      pragmatic, interdisciplinary solutions for these deep-rooted dilemmas. In the
      interests of all stakeholders, I seek to promote a concerted effort to resolve
      conflict and build consensus. METHODS: This paper explores a strategically
      unifying vision of primary care, based on current understanding of practice
      patterns, having a research-friendly 'common ground' where practitioners'
      information needs may be met. In addition, an analysis of existing problems
      identifies underlying 'root causes'. Moreover, I expediently reframe crucial
      matters by focusing on EBM, more than as a paradigm, as an organisation, hence
      amenable to a variety of cross-disciplinary analyses and solutions. Finally,
      recent state-of-the-art reviews on implementation and dissemination research are
      cited for the pertinent implications for study design and practice. RESULTS:
      Present policies and influential testimonials on behalf of EBM encounter the
      pitfalls of hindering learning and progress through defensive attitudes and
      mechanisms. Current study designs and evaluation criteria must strive to adapt to
      real-world settings, rather than vice versa. CONCLUSIONS: The arguments exposed
      herein alter the terms of the debate on EBM and may outline a basis for
      initiatives with conflict-resolution and consensus-building scopes.

PMID- 16907688
TI  - Reductionist inference-based medicine, i.e. EBM.
AB  - RATIONALE, AIMS AND OBJECTIVES: Unbeknown to many, reductionist and postmodern
      worldviews competitively coexist in science and society. The debate on evidence
      based medicine (EBM) is at the tip of this 'iceberg'. Via systems thinking and
      complexity science EBM reveals crucial flaws and its reductionism entails an
      inability to appreciate (even tolerate) contrasting ideas and/or 'see a bigger
      picture'. An interdisciplinary approach provides insight into novel explanations.
      Thereafter, the conceptual barrier shifts to communication, a challenge which
      mandates attempts to steer the discourse by reframing the debate. METHOD:
      Interdisciplinary perspectives serve to illustrate a 'bigger picture'. Also,
      'wicked' questions stimulate reflection, discern leverage points and dismantle
      resilient defences. Lastly, a proposal: exploring the value of 'glasses half
      full'. CONCLUSION: Some may realize that postmodern concepts behind compelling
      criticisms to EBM have already taken root, being shared by policymakers,
      practitioners and patients as well.

PMID- 16907689
TI  - External validity: the neglected dimension in evidence ranking.
AB  - Evidence that is both accurate (internally valid) and relevant (externally valid)
      is needed to decide which treatment is best for a particular patient. Evidence
      rankings facilitate the marshalling of evidence on clinical decisions in the
      common context of an overwhelming number of studies, some with conflicting
      results. Evidence from randomized control trials is typically ranked above
      evidence from non-experimental studies since rankings are based primarily, if not
      exclusively, on considerations of internal validity. We propose that evidence
      rankings should consider equally both internal and external validity. External
      validity includes how closely the study population, the institution types in the
      study, the types of physicians in the study, the role of clinician decision
      making (e.g. dose adjustment) in the study, and the role of patient preferences
      in the study resemble those in actual practice. The example of spironolactone use
      in heart failure illustrates the danger in using evidence that is internally but
      not externally valid. Ideally, a treatment should only be used when both
      internally and externally valid evidence indicates that it will be useful for the
      particular patient.

PMID- 16907691
TI  - A comparison between integrating clinical practice setting and randomized
      controlled trial setting into economic evaluation models of therapeutics.
AB  - BACKGROUND: Cost-effectiveness analyses generated from randomized controlled
      trials (RCTs) represent results obtained under ideal experimental conditions
      (efficacy) and the applicability of these data to real-world settings
      (effectiveness) may be questionable. OBJECTIVE: To compare cost-effectiveness
      results obtained from a RCT setting with the results derived from community-based
      clinical practice. METHODS: Using data from a community-based cohort study and
      from a RCT, two cost-effectiveness analyses were performed and the incremental
      cost-effectiveness ratios (ICERs) were calculated for the use of etanercept in
      the treatment of patients with rheumatoid arthritis. RESULTS: Using an
      effectiveness-based analysis, the mean quality-adjusted life years (QALYs) gained
      during the 12-month monitoring period were 0.45 and 0.35 for the treatment and
      control groups respectively. The ICER for etanercept treatment was 174,200
      dollars (CDN) per QALY (95% confidence limits between 119,500 dollars and 285,000
      dollars). Incorporating efficacy data obtained from the RCT into the analysis,
      the mean QALYs gained were 0.56 and 0.35 for the treatment and control groups
      respectively. This resulted in a substantially lower ICER for etanercept
      treatment of 82,952 dollars per QALY (95% confidence limits between 66,500
      dollars and 103,430 dollars). CONCLUSION: Depending on the type of clinical
      setting used for the analysis, the resulting ICER for etanercept treatment was
      very different. These results help to explain the difference in cost
      effectiveness reported in previous modeling studies, some based on RCT
      assumptions and some based on effectiveness setting.

PMID- 16907690
TI  - Research results have expiration dates: ensuring timely systematic reviews.
AB  - Time and timeliness are key issues in appraising and ensuring the clinical
      relevance of systematic reviews. Time considerations entering the systematic
      review process include the history of the clinical problem, disease, or treatment
      that is the target of the review, and the history of the research conducted to
      address it. These considerations guide: (i) formulation of the research problems
      and questions; (ii) setting of parameters for the search and retrieval of
      studies; (iii) determination of inclusion and exclusion criteria; (iv) appraisal
      of the clinical relevance of findings; (v) selection of the findings that will be
      synthesized; and (vi) interpretation of the results of that synthesis.

PMID- 16907693
TI  - Primary care telehealth practice.

PMID- 16907694
TI  - Teaching nurse practitioners how to teach patients to take responsibility.

PMID- 16907695
TI  - Machismo sustains health and illness beliefs of Mexican American men.
AB  - PURPOSE: To inform nurse practitioners (NPs) about Mexican American men's health
      and illness beliefs and the ways in which these are influenced by their masculine
      identity and how they view themselves as men in their culture. DATA SOURCES: The
      data sources used were based on a selected review of the literature about Mexican
      American men's health and illness beliefs and the concept of machismo. Several
      studies, including the author's study on Mexican American men's healthcare
      seeking beliefs and behaviors and experience in providing primary health care to
      men across cultures, contributed new data. CONCLUSIONS: The meaning of manhood in
      the Mexican American culture is critical in understanding how men perceive health
      and illness and what they do when they are ill. Machismo enhances men's awareness
      of their health because they have to be healthy to be good fathers, husbands,
      brothers, sons, workers, and community members. Pain and disability are
      motivating factors in finding ways to regain their health. IMPLICATIONS FOR
      PRACTICE: Men's health beliefs across cultures need further investigation by
      nurse researchers and NPs. How culture influences healthcare delivery to men
      should be better understood. If NPs are aware of men's views on masculinity, they
      are better prepared to understand and assist men in becoming more aware of their
      health status and to seek health care when appropriate.

PMID- 16907696
TI  - An evaluation of dementia screening in the primary care setting.
AB  - PURPOSE: To evaluate current screening methods for dementia to determine the most
      accurate and efficient tools for use in primary care. DATA SOURCES: Search
      included the following: Medline, CINAHL, BIOSIS, PsycINFO, ISI Web of Science,
      and Health & Psychosocial Instruments (1840-2005). The following search terms
      were used: screen, screening, tools, Mini Mental, MMSE, clock drawing, subjective
      memory, assessment, diagnosis, primary care, outpatient, community based,
      ambulatory care, dementia, cognitive impairment, and memory impairment. There was
      no limit to publication year. Articles excluded were those not published in
      English and those which used screening tools as part of diagnostic evaluation.
      The search revealed 581 relevant articles, which were narrowed to 20.
      CONCLUSIONS: The Mini Mental State Examination (MMSE) has high sensitivity and
      specificity in outpatients older than 65 years when age- and education-specific
      cutoffs are used. The clock drawing test has lower sensitivity and specificity
      when used alone; however, in combination with the MMSE, its sensitivity is higher
      than that of the MMSE while specificity is slightly lower. Subjective memory
      complaints contribute diagnostic information; however, objective memory
      performance is a stronger predictor of future dementia. All measures are subject
      to influence by age, education, and other physical factors. The body of evidence
      regarding dementia screening methods has increased in recent years. The studies
      have been well conducted, of large sample size, in various geographic locations
      and populations, and by numerous investigators. IMPLICATIONS FOR PRACTICE:
      Dementing illnesses will become a common presentation in primary care. Currently,
      routine screening is not conducted although acceptable instruments, such as the
      MMSE, are available. Additional research on routine screening in primary care to
      bolster the current evidence, use of nurses as evaluators of cognition, and
      utilization of specialists is needed.

PMID- 16907697
TI  - Uterine artery embolization as a treatment for symptomatic uterine fibroids: a
      review of literature and case report.
AB  - PURPOSE: To provide a case presentation and review of the literature on uterine
      artery embolization (UAE) as a treatment alternative for symptomatic uterine
      fibroids and to guide the nurse practitioner (NP) in patient selection,
      education, and periprocedural management of patients undergoing this procedure.
      DATA SOURCES: Research articles, clinical articles, and case studies pertaining
      to UAE. CONCLUSIONS: UAE is a safe, well tolerated, and effective nonsurgical
      treatment option for symptomatic uterine fibroids. This uterus-sparing procedure
      has low complication rates with excellent clinical outcomes and high patient
      satisfaction rates. The majority of women who undergo UAE report marked reduction
      in the severity of fibroid specific symptoms and significant improvement in their
      quality of life. Uterine fibroids are common in women and often produce symptoms
      that have a negative impact on quality of life. IMPLICATIONS FOR PRACTICE: The NP
      is instrumental in identifying which patients may be appropriate candidates for
      UAE, educating them about the risks and benefits of the procedure, and managing
      these patients before and after the procedure.

PMID- 16907698
TI  - Bipolar disorder: etiology, diagnosis, and management.
AB  - PURPOSE: To review the epidemiology and disease characteristics of the bipolar
      disorder (BD) spectrum, render an accurate and timely diagnosis, and review
      treatment options through provider and patient collaboration. DATA SOURCES:
      Comprehensive review of current scientific literature derived from electronic
      databases and professional medical references. CONCLUSIONS: BD is a
      multifactorial disease that can interfere with cognition and behavior, causing a
      severe impact on patients and families. The variable course and often delayed
      diagnosis of this disorder can cause frustration for the patient and the
      healthcare provider. Because most undiagnosed patients with BD seek treatment
      within the primary care setting, it is imperative that clinicians become expert
      in the recognition of and intervention for this condition. IMPLICATIONS FOR
      PRACTICE: The primary care provider is in a key position to render early
      diagnosis and treatment of BD. This disease should always be considered as part
      of the differential diagnosis for depression or anxiety. Nurse practitioners can
      be effective providers by using good nursing practices of communication,
      education, and advocacy for the patient and family. Knowledge of current
      diagnostic criteria and management is imperative for successful treatment of
      patients with BD.

PMID- 16907699
TI  - Health information and risk behaviors among lesbian, gay, and bisexual college
      students.
AB  - PURPOSE: To describe differences in alcohol use, marijuana use, and smoking
      behaviors between lesbian, gay, and bisexual (LGB) and heterosexual college
      students, and determine whether there was a difference in the health information
      each group received. DATA SOURCES: A random sample of 3000 college students aged
      18-24 years who were currently enrolled at a southeastern metropolitan university
      on a full-time basis were invited to participate. The final sample (n = 772)
      consisted of heterosexuals (n = 731) and LGB (n = 41) college students. Gay and
      bisexual men (n = 20) and lesbian and bisexual women (n = 21) were compared to
      heterosexual college students. CONCLUSIONS: Lesbian/bisexual women were 4.9 times
      more likely to smoke, 10.7 times more likely to drink, and 4.9 times more likely
      to use marijuana than heterosexual women. Gay/bisexual men did not significantly
      differ from heterosexual men. There was no difference in the health information
      on alcohol and drug prevention the groups received. Gay/bisexual men were less
      likely (p = .02) compared to heterosexual men to have received tobacco prevention
      information. IMPLICATION FOR PRACTICE: Advanced practice nurses must ensure that
      every patient receives preventive services and anticipatory guidance at every
      visit. LGB clients in particular need health assessments and interventions
      appropriate to their individual risk profiles.

PMID- 16907700
TI  - Spiritual care practices of nurse practitioners in federally designated
      nonmetropolitan areas of North Carolina.
AB  - PURPOSE: The purpose of this study was to explore if and then how nurse
      practitioners (NPs) living in federally designated nonmetropolitan areas of North
      Carolina integrated spiritual care into their practices. Participants identified
      the frequency in which they utilize spiritual care practices, specific spiritual
      interventions, and their definitions of spiritual care. DATA SOURCES: A sample of
      101 NPs was chosen through systematic sampling from 507 eligible NPs. Each
      participant was mailed a demographic data sheet and the Nurse Practitioner
      Spiritual Care Perspective Survey (NPSCPS). The NPSCPS was modified from the
      Oncology Nurse Spiritual Care Perspective Scale developed by Taylor and
      colleagues. Of the 101 mailings, 65 were returned and included in the analysis.
      CONCLUSIONS: Although most of the NPs in this study felt that spiritual care was
      an important part of nursing practice, 73% did not routinely provide spiritual
      care to their patients. Barriers and limitations to the provision of spiritual
      care must be explored. IMPLICATIONS FOR PRACTICE: As providers of holistic care,
      NPs should be proficient and comfortable in providing spiritual care to their
      patients. Educational programs should provide NPs and NP students with knowledge
      and skills to provide spiritual care.

PMID- 16907701
TI  - Determining predictors of delayed recovery and the need for transitional cardiac
      rehabilitation after cardiac surgery.
AB  - PURPOSE: To examine the relationship between demographic and clinical
      characteristics of cardiac surgery patients with postoperative length of stay
      (PLOS) greater than 7 days and determine the demographic, social, and clinical
      predictors of the need for transitional cardiac rehabilitation (TCR) after
      cardiac surgery. DATA SOURCES: A retrospective review of characteristics,
      clinical indices, caregiver availability, and patient status (whether living
      alone) was completed for 304 patients undergoing cardiac surgery over 24
      consecutive months. Univariate analyses and multivariable logistic regression
      models were used to evaluate risk factor characteristics for PLOS greater than 7
      days and to predict discharge disposition to TCR or home. CONCLUSIONS: Older
      patients, those with preoperative comorbidities, and those without a caregiver at
      home experience delays in functional recovery and discharge and are more likely
      to need TCR services. IMPLICATIONS FOR PRACTICE: Our findings support the
      addition of functional recovery and social support risk items to the preoperative
      cardiac surgery risk assessment.

PMID- 16907702
TI  - Investigating the relationship between FMR1 allele length and cognitive ability
      in children: a subtle effect of the normal allele range on the normal ability
      range?
AB  - The FMR1 gene contains a trinucleotide repeat tract which can expand from a
      normal size of around 30 repeats to over 200 repeats, causing mental retardation
      (Fragile X Syndrome). Evidence suggests that premutation males (55-200 repeats)
      are susceptible to a late-onset tremor/ataxia syndrome and females to premature
      ovarian failure, and that intermediate alleles ( approximately 41-55 repeats) and
      premutations may be in excess in samples with special educational needs. We
      explored the relationship between FMR1 allele length and cognitive ability in 621
      low ability and control children assessed at 4 and 7 years, as well as 122
      students with high IQ. The low and high ability and control samples showed no
      between-group differences in incidence of longer alleles. In males there was a
      significant negative correlation between allele length and non-verbal ability at
      4 years (p = 0.048), academic achievement in maths (p = 0.003) and English (p =
      0.011) at 7 years, and IQ in the high ability group (p = 0.018). There was a
      significant negative correlation between allele length and a standardised score
      for IQ and general cognitive ability at age 7 in the entire male sample (p =
      0.002). This suggests that, within the normal spectrum of allele length,
      increased repeat numbers may have a limiting influence on cognitive performance.

PMID- 16907703
TI  - Adrenergic receptor polymorphisms associated with resting heart rate: the
      HyperGEN Study.
AB  - The association between polymorphisms in the beta1, beta2 and alpha2B adrenergic
      receptor (ADR) genes (ADRB1, ADRB2 and ADRA2B) and resting heart rate was
      examined in white and African-American participants of the HyperGEN Study. All
      analyses were adjusted for age, sex, body mass index, alcohol use, smoking status
      and daily exercise within strata of race, hypertension status and beta-blocker
      use. The Ser49Gly polymorphism of the beta1 ADR was associated with resting heart
      rate in hypertensive African-Americans and hypertensive whites taking beta
      blockers, with carriers of the Gly allele having a higher mean resting heart rate
      by 2.7 and 4.4 beats per minute (bpm), respectively. The Arg389Gly polymorphism
      of the beta1 ADR was associated with lower heart rate in the normotensive African
      American sample. A beta1 haplotype (Ser49Gly-Arg389Gly) was modestly associated
      with resting heart rate in the hypertensive African-Americans. The alpha2B C/A
      polymorphism was associated with heart rate in hypertensive whites, and both
      whites and African-Americans taking beta-blockers, with carriers of the A allele
      having a higher mean resting heart rate. In summary, each of the ADR gene
      polymorphisms was associated with heart rate in at least one stratum studied, but
      there was no consistent association from which one would infer a large genetic
      contribution to heart rate.

PMID- 16907704
TI  - Lack of association between genetic variation in 9 innate immunity genes and
      baseline CRP levels.
AB  - It is well-known that baseline levels of C-reactive protein (CRP) are an
      independent cardiovascular risk factor. We hypothesized that genetic variation
      with significant influence on CRP levels might be found in genes of the innate
      immunity system. We performed a candidate gene association study examining common
      single nucleotide polymorphisms in 9 innate immunity genes (CARD15, IRAK1, IRAK4,
      LBP, LY86, MEFV, TLR2, TLR4 and NFKB1) in relation to CRP levels. Seven hundred
      and seventeen subjects from the Women's Health Study population were studied: 359
      and 358 samples with extremely low (<0.2 mg/liter) and high (>5 mg/liter) CRP
      levels, respectively. SNPs were identified from publicly available resequencing
      data, using a minor allele frequency threshold of >5% and a linkage
      disequilibrium (LD)-based strategy (r(2) > 0.8) to select 63 LD-independent
      markers. One non-synonymous SNP in TLR4 and two non-synonymous SNPs in CARD15,
      previously associated with atherosclerosis and Crohn's disease, respectively,
      were also studied. Univariate, haplotype and gene-gene interaction analyses all
      indicated no significant association with CRP levels. Although this work excludes
      a significant association of common SNPs in these nine genes with CRP levels, it
      is possible that rarer alleles in these genes, or variation in other innate
      immunity genes, could be associated with variation in CRP.

PMID- 16907705
TI  - Examination of PPP1R3B as a candidate gene for the type 2 diabetes and MODY loci
      on chromosome 8p23.
AB  - The product of the PPP1R3B gene (G(L)) is the regulatory subunit of PP1 - a
      serine/threonine phosphatase involved in the modulation of glycogen synthesis in
      the liver and skeletal muscle. The PPP1R3B gene is located on chromosome 8p23 in
      a region that has been linked with type 2 diabetes and maturity-onset diabetes of
      the young (MODY). We examined whether sequence variants at the PPP1R3B locus are
      responsible for the linkage with diabetes observed at this location. RT-PCR
      analysis revealed the existence of two alternative promoters. These and the two
      exons of this gene were sequenced in the probands of 13 Joslin families showing
      the strongest evidence of linkage at 8p23. A total of 20 variants were observed:
      two in the 5' flanking region, one in the intron (9 bp 5' of exon 2), and 17 in
      the 3' UTR. The intronic variant generated a new acceptor splice site, resulting
      in an alternative splice variant with a longer 5' UTR. However, neither this nor
      other variants segregated with diabetes in the 13 'linked' families. Furthermore,
      allele frequencies were similar in 90 family probands from the Joslin Study and
      347 unrelated controls. Thus, genetic variability in the PPP1R3B gene does not
      appear to contribute to diabetes in our mostly Caucasian families. However, a
      role cannot be excluded in other populations such as the Japanese, among whom
      linkage to diabetes is also observed at 8p23 and a non-synonymous mutation has
      been detected in the PPP1R3B gene.

PMID- 16907706
TI  - Geographical variations in TP53 mutational spectrum in ovarian carcinomas.
AB  - The TP53 gene mutational spectrum in human tumours shows variations related to
      tissue of origin, carcinogen exposure or molecular background. We have compared
      TP53 mutations in ovarian carcinomas from different geographical regions; this
      study was based on data extracted and verified from the IARC database (R10,
      2005), and on our results from 127 carcinomas. In total 873 mutations were
      evaluated. Tumours from Japan and Korea had a higher frequency of exon 7
      mutations (38%vs 25%, p = 0.011) and lower frequency of exon 8 mutations (11%vs
      29%, p = 0.0003) than those from Western countries; they were particularly
      different from Norwegian tumours which showed the lowest proportion of exon 7
      (19%, p = 0.001) and highest proportion of exon 8 (37%, p < 0.0001) mutations.
      There were also differences in the profile of TP53 hotspots. The third hotspot in
      tumours from Poland was amino acid (AA) 176 (8.2% of substitutions vs 1.7% in
      other countries, p < 0.001), while in tumours from the UK it was AA 220 (8.9%vs
      2.3%, p < 0.001). Codon 273 was the only apparent hotspot in the Norwegian
      tumours, while it was rarely mutated in Polish and Asian tumours. In contrast to
      other data tumours from Norway presented with 273(HIS) codon (82% of mutations at
      AA 273, p = 0.002), while tumours from the UK shared the 273(CYS) codon (80%, p <
      0.001). Further analysis of TP53 gene mutations in ovarian cancer by geography
      could provide greater insights.

PMID- 16907708
TI  - OCA1 in different ethnic groups of india is primarily due to founder mutations in
      the tyrosinase gene.
AB  - Oculocutaneous albinism (OCA) is a heterogeneous group of autosomal recessive
      disorders characterized by an abnormally low amount of melanin in the eyes, skin
      and hair, and associated with common developmental abnormalities of the eye.
      Defects in the tyrosinase gene (TYR) cause a common type of OCA, known as
      oculocutaneous albinism type 1 (OCA1). The molecular basis of OCA has been
      studied extensively in different population groups, but very little information
      is available on Indian patients. Our investigation covering thirteen ethnic
      groups of India, some representing >20 million people, revealed that among 25 OCA
      families 12 were affected with OCA1, and that these cases were primarily due to
      founder mutations in TYR. We detected nine mutations and eight SNPs in TYR, of
      which six mutations (five point mutations & one gross deletion) were novel. In
      contrast to most reports describing compound heterozygotes, the presence of
      homozygotes in 10 out of the 12 pedigrees underscores the lack of intermixing
      between these ethnic groups in India. Haplotype analysis suggested a few founder
      chromosomes causing the disease in the majority of the patients. Direct detection
      of the mutations prevalent in specific ethnic groups could be used for carrier
      detection and genetic counselling.

PMID- 16907707
TI  - Genetic variations and haplotype structures of the ABCB1 gene in a Japanese
      population: an expanded haplotype block covering the distal promoter region, and
      associated ethnic differences.
AB  - As functional ABCB1 haplotypes were recently reported in the promoter region of
      the gene, we resequenced the ABCB1 distal promoter region, along with other
      regions (the enhancer and proximal promoter regions, and all 28 exons), in a
      total of 533 Japanese subjects. Linkage disequilibrium (LD) analysis based on 92
      genetic variations revealed 4 LD blocks with the same make up as previously
      described (Blocks -1, 1, 2 and 3), except that Block 1 was expanded to include
      the distal promoter region, and that a new linkage between polymorphisms 
      1,789G>A in the distal promoter region and IVS5 + 123A>G in intron 5 was
      identified. We re-assigned Block 1 haplotypes, and added novel haplotypes to the
      other 3 blocks. The reported promoter haplotypes were further classified into
      several types according to tagging variations within Block 1 coding or intronic
      regions. Our current data reconfirm the haplotype profiles of the other three
      blocks, add more detailed information on functionally-important haplotypes in
      Block 1 and 2 in the Japanese population, and identified differences in haplotype
      profiles between ethnic groups. Our updated analysis of ABCB1 haplotype blocks
      will assist pharmacogenetic and disease-association studies carried out using
      Asian subjects.

PMID- 16907709
TI  - Mitochondrial DNA variation in Mauritania and Mali and their genetic relationship
      to other Western Africa populations.
AB  - Mitochondrial DNA (mtDNA) variation was analyzed in Mauritania and Mali, and
      compared to other West African samples covering the considerable geographic,
      ethnic and linguistic diversity of this region. The Mauritanian mtDNA profile
      shows that 55% of their lineages have a west Eurasian provenance, with the U6
      cluster (17%) being the best represented. Only 6% of the sub-Saharan sequences
      belong to the L3A haplogroup a frequency similar to other Berber speaking groups
      but significantly different to the Arabic speaking North Africans. The historic
      Arab slave trade may be the main cause of this difference. Only one HV west
      Eurasian lineage has been detected in Mali but 40% of the sub-Saharan sequences
      belong to cluster L3A. The presence of L0a representatives demonstrates gene flow
      from eastern regions. Although both groups speak related dialects of the Mande
      branch, significant genetic differences exist between the Bambara and Malinke
      groups. The West African genetic variation is well structured by geography and
      language, but more detailed ethnolinguistic clustering suggest that geography is
      the main factor responsible for this differentiation.

PMID- 16907710
TI  - The genetic structure of human populations studied through short insertion
      deletion polymorphisms.
AB  - In a landmark study Rosenberg et al. (2002) analyzed human genome diversity with
      377 microsatellites in the HGDP-CEPH Genome Diversity Panel and reported that the
      populations were structured into five geographical regions: America, Sub-Saharan
      Africa, East Asia, Oceania and a cluster composed of Europe, the Middle East and
      Central Asia. They also observed that the within-population component accounted
      for 93-95%, and that the among-regions portion was only 3.6%, of the total
      genetic variance. We have also studied the HGDP-CEPH Diversity Panel (1,064
      individuals from 52 populations) with a set of 40 biallelic slow-evolving short
      insertion-deletion polymorphisms (indels). We confirmed the partition of
      worldwide diversity into five genetic clusters that correspond to major
      geographic regions. Using the indels we have also disclosed an among-regions
      component of genetic variance considerably larger (12.1%) than had been estimated
      using microsatellites. Our study demonstrates that a set of 40 well-chosen
      biallelic markers is sufficient for the characterization of human population
      structure at the global level.

PMID- 16907711
TI  - Estimating human inbreeding coefficients: comparison of genealogical and marker
      heterozygosity approaches.
AB  - We have used genealogies and genomic polymorphisms to estimate individual
      inbreeding coefficients (F) in 50 subjects with an expected range (based on
      recent genealogies) of F from 0.0 to 0.0625. The estimates were based on two
      approaches, using genotypes respectively from 410 microsatellite markers (410-STR
      panel) and from 10,000 SNPs (10K-SNP panel). The latter was performed in a sub
      sample of 15 individuals. We concluded that for both marker panels measures of
      inbreeding based on the excess of homozygosity over Hardy-Weinberg expectation
      were not closely correlated with 4-5 generation genealogical F-values. For the
      10K-SNP panel we found two alternative measures which correlated more closely
      with F, based respectively on standard errors and on paired homozygosity of
      nearby SNPs over distances of 2-4 cM. We propose an empirical method for
      estimating standard errors and hence individual F-values, based on the variation
      between individual autosomes. This method could provide useful estimates of
      average F-values for groups of individuals in population-based studies of the
      effects of inbreeding/homozygosity on quantitative traits.

PMID- 16907712
TI  - A combinatorial searching method for detecting a set of interacting loci
      associated with complex traits.
AB  - Complex diseases are presumed to be the results of the interaction of several
      genes and environmental factors, with each gene only having a small effect on the
      disease. Mapping complex disease genes therefore becomes one of the greatest
      challenges facing geneticists. Most current approaches of association studies
      essentially evaluate one marker or one gene (haplotype approach) at a time. These
      approaches ignore the possibility that effects of multilocus functional genetic
      units may play a larger role than a single-locus effect in determining trait
      variability. In this article, we propose a Combinatorial Searching Method (CSM)
      to detect a set of interacting loci (may be unlinked) that predicts the complex
      trait. In the application of the CSM, a simple filter is used to filter all the
      possible locus-sets and retain the candidate locus-sets, then a new objective
      function based on the cross-validation and partitions of the multi-locus
      genotypes is proposed to evaluate the retained locus-sets. The locus-set with the
      largest value of the objective function is the final locus-set and a permutation
      procedure is performed to evaluate the overall p-value of the test for
      association between the final locus-set and the trait. The performance of the
      method is evaluated by simulation studies as well as by being applied to a real
      data set. The simulation studies show that the CSM has reasonable power to detect
      high-order interactions. When the CSM is applied to a real data set to detect the
      locus-set (among the 13 loci in the ACE gene) that predicts systolic blood
      pressure (SBP) or diastolic blood pressure (DBP), we found that a four-locus gene
      gene interaction model best predicts SBP with an overall p-value = 0.033, and
      similarly a two-locus gene-gene interaction model best predicts DBP with an
      overall p-value = 0.045.

PMID- 16907713
TI  - Genetic heterogeneity of beta-thalassemia in Lebanon.

PMID- 16907715
TI  - Contrasting signal transduction mechanisms in bacterial and eukaryotic gene
      transcription.
AB  - All known cell types use signal transduction systems to respond to an
      extracellular or intracellular event. The role of these systems can be to adapt
      to environmental changes or simply to maintain homeostasis. Cells detect and
      respond to stimuli in a number of ways. Here we review the mechanisms involved in
      the transmission of a signal from point of detection to site of action. In
      particular, a comparison is made between the signalling networks which function
      in gene transcription in bacterial and eukaryotic cells. Knowledge of the
      similarities between the systems found in the two types of cells can provide a
      better understanding of the function and origin of signalling components. In
      addition, the divergence evident can be exploited by molecules that modulate or
      disrupt the function of differential signalling mechanisms.

PMID- 16907716
TI  - Phytophthora polonica, a new species isolated from declining Alnus glutinosa
      stands in Poland.
AB  - In a survey of Phytophthora associated with alder decline in Poland, several
      isolates of a homothallic Phytophthora sp., which could not be assigned to other
      taxa including Phytophthora alni subspecies, were consistently recovered from
      rhizosphere soil samples. Their morphology and pathogenicity, as well as sequence
      data for three nuclear regions (internal transcribed spacer rDNA, elongation
      factor-1alpha and beta-tubulin) and a coding mitochondrial DNA region (nadh1),
      were examined. The new Phytophthora species is characterized by the moderate to
      slow growth rate of its colony in carrot agar at 20 degrees C, high optimal (c.
      30 degrees C) and maximum (c. 38 degrees C) growth temperatures, formation of
      catenulate, often lateral, hyphal swellings, large chlamydospores in agar media
      and in soil extract, persistent, ovoid to ellipsoid nonpapillate sporangia and
      large oogonia with paragynous and sometimes amphigynous antheridia. Phytophthora
      polonica was slightly pathogenic to alder twigs and not pathogenic to trunks of
      several tree species. In a phylogenetic analysis using either Bayesian inference
      or maximum likelihood methods, P. polonica falls in clade 8 'sensu Kroon et al.
      (2004)' of Phytophthora.

PMID- 16907717
TI  - The expression of cytochrome P-450 and cytochrome P-450 reductase genes in the
      simultaneous transformation of corticosteroids and phenanthrene by Cunninghamella
      elegans.
AB  - The expression of cytochrome P-450 and cytochrome P-450 reductase (CPR) genes in
      the conterminous biotransformation of corticosteroids and PAHs was studied in
      Cunninghamella elegans 1785/21Gp. We had previously used this strain as a
      microbial eucaryotic model for studying the relationship between mammalian
      steroid hydroxylation and the metabolization of PAHs. We reported that cytochrome
      P-450 reductase is involved in the biotransformaton of cortexolone and
      phenanthrene. RT-PCR and Northern blotting analyses indicated that the cytochrome
      P-450 and CPR genes appear to be inducible by both steroids and PAHs. The
      expression of the cytochrome P-450 gene was increased ninefold and the expression
      of the CPR gene increased 6.4-fold in cultures with cortexolone and/or
      phenanthrene in comparison with controls. We conclude that the increase in
      cytochrome P-450 gene expression was accompanied by an increase in cytochrome P
      450 enzymatic activity levels.

PMID- 16907718
TI  - Azole antifungals as novel chemotherapeutic agents against murine tuberculosis.
AB  - The present study was designed to evaluate the in vivo antimycobacterial
      potential of econazole alone and in combination with antitubercular drugs against
      tuberculosis in mice. Econazole was found to reduce bacterial burden by 90% in
      the lungs and spleen of mice infected with 1 x 10(7) cells of Mycobacterium
      tuberculosis and was found to be equipotent to rifampicin. Further, our results
      indicate that econazole can replace rifampicin/isoniazid as well as both
      rifampicin and isoniazid in chemotherapy of murine tuberculosis. Econazole alone
      or in combination with antitubercular drugs did not produce any hepatotoxicity in
      normal or M. tuberculosis-infected mice.

PMID- 16907719
TI  - Recombinant expression and characterization of a Xylella fastidiosa cysteine
      protease differentially expressed in a nonpathogenic strain.
AB  - Xylella fastidiosa is a xylem-limited, Gram-negative bacterium responsible for
      citrus variegated chlorosis (CVC) in sweet oranges. In the present study, we
      present the recombinant expression, purification and characterization of an X.
      fastidiosa cysteine protease (dubbed Xylellain). The recombinant Xylellain
      ((HIS)Xylellain) was able to hydrolyze carbobenzoxy-Phe-Arg-7-amido-4
      methylcoumarin (Z-FR-MCA) and carbobenzoxy-Arg-Arg-7-amido-4-methylcoumarin (Z-RR
      MCA) with similar catalytic efficiencies, suggesting that this enzyme presents
      substrate specificity requirements similar to cathepsin B. The immunization of
      mice with (HIS)Xylellain provided us with antibodies, which recognized a protein
      of c. 31 kDa in the X. fastidiosa pathogenic strains 9a5c, and X. fastidiosa
      isolated from coffee plants. However, these antibodies recognized no protein in
      the nonpathogenic X. fastidiosa J1a12, suggesting the absence or low expression
      of this protein in the strain. These findings enabled us to identify Xylellain as
      a putative target for combating CVC and other diseases caused by X. fastidiosa
      strains.

PMID- 16907720
TI  - Siro(haem)amide in Allochromatium vinosum and relevance of DsrL and DsrN, a
      homolog of cobyrinic acid a,c-diamide synthase, for sulphur oxidation.
AB  - In the purple sulphur bacterium Allochromatium vinosum, the prosthetic group of
      dissimilatory sulphite reductase (DsrAB) was identified as siroamide, an amidated
      form of the classical sirohaem. The genes dsrAB are the first two of a large
      cluster of genes necessary for the oxidation of sulphur globules stored
      intracellularly during growth on sulphide and thiosulphate. DsrN is homologous to
      cobyrinic acid a,c diamide synthase and may therefore catalyze glutamine
      dependent amidation of sirohaem. Indeed, an A. vinosumDeltadsrN in frame deletion
      mutant showed a significantly reduced sulphur oxidation rate that was fully
      restored upon complementation with dsrN in trans. Sulphite reductase was still
      present in the DeltadsrN mutant. DsrL is a homolog of the small subunits of
      bacterial glutamate synthases and was proposed to deliver glutamine for sirohaem
      amidation. However, recombinant DsrL does not exhibit glutamate synthase activity
      nor does the gene complement a glutamate synthase-deficient Escherichia coli
      strain. Deletion of dsrL showed that the encoded protein is absolutely essential
      for sulphur oxidation in A. vinosum.

PMID- 16907721
TI  - High-level production and purification of a fully active recombinant
      dextransucrase from Leuconostoc mesenteroides NRRL B-512F.
AB  - Recombinant expression of the dextransucrase dsrS gene by Escherichia coli was
      optimized to produce 5850 U L(-1) (culture) of DSR-S, corresponding to a 30-fold
      increase compared with previous studies. Rational deletions of the signal
      peptide, the beginning of the variable region and the last four repeats of the C
      terminal end caused no loss of activity. This new variant successfully purified
      was remarkably stable. With a k(cat) of 584 s(-1), it is the most efficient
      recombinant glucansucrase described to date. The synthesized polymer possesses
      more than 95% of alpha-1,6 links, like the dextran produced by the native enzyme,
      and innovative gel properties were obtained.

PMID- 16907722
TI  - The Bacteroides fragilis P20 scavengase homolog is important in the oxidative
      stress response but is not controlled by OxyR.
AB  - The oxidative stress response of obligate anaerobe, Bacteroides fragilis, is
      partially controlled by the redox regulator OxyR but an oxyR null mutant
      maintains a high level of aerotolerance. Studies using two-dimensional
      polyacrylamide gel electrophoresis showed that a thiol peroxidase-scavengase,
      Tps, was induced during oxygen exposure of an oxyR mutant. Tps is similar to
      'atypical 2-cysteine peroxidases' such as scavengase p20 and it demonstrated
      catalytic activity against t-butyl hydroperoxide and H(2)O(2). A second gene,
      oim, encoding a putative membrane protein, was divergently transcribed from tps.
      Transcriptional analysis indicated that tps and oim were coordinately regulated
      by oxygen induction via an OxyR-independent mechanism. H(2)O(2) was a less potent
      inducer than oxygen exposure and in an oxyR mutant the mRNA levels were slightly
      reduced compared with the wild type. A null mutant of tps had increased
      sensitivity to killing by t-butyl hydroperoxide and oxygen but an oim mutant was
      similar to wild type. These data indicate that Tps is important for protection
      against some forms of oxidative stress.

PMID- 16907723
TI  - Neoplaether, a new cytotoxic and antifungal endophyte metabolite from
      Neoplaconema napellum IFB-E016.
AB  - A new diphenyl ether, named neoplaether, together with five known compounds
      monomethylsulochrin, physcion, helvolic acid, ergosterol and ergosterol peroxide,
      was isolated from the culture of Neoplaconema napellum IFB-E016, an endophytic
      fungus residing in the healthy leaves of Hopea hainanensis. The structure of
      neoplaether was elucidated by a correlative interpretation of its infrared
      spectrometry, mass spectroscopy and nuclear magnetic resonance spectra, and
      confirmed by its single-crystal X-ray diffraction analysis. Neoplaether exhibited
      significant cytotoxic activity against the human nasopharyngeal epidermoid tumor
      KB cell line, with an IC(50) value of 13.0 microg mL(-1), comparable to that of 5
      fluorouracil (2.5 microg mL(-1)) co-assayed as a positive reference. In addition,
      it showed antifungal activity against Candida albicans, with a minimal inhibitory
      concentration value of 6.2 microg mL(-1) (amphotericin as a positive control had
      a value of 1.5 microg mL(-1)).

PMID- 16907724
TI  - Construction and characterization of a bifunctional fusion enzyme of Bacillus
      sourced beta-glucanase and xylanase expressed in Escherichia coli.
AB  - A chimeric gene, Glu-Xyl, encoding Bacillus amyloliquefaciens glucanase (Glu,
      24.4 kDa) and Bacillus subtilis xylanase (Xyl, 21.2 kDa), was constructed via end
      to-end fusion and expressed successfully in Escherichia coli. The purified fusion
      protein (46.1 kDa) exhibited both glucanase and xylanase activities. Compared
      with parental enzymes, the Glu moiety was characterized by kinetic parameters of
      decreased K(m) (0.66-fold) and increased K(cat) (2.75-fold), whereas the Xyl
      moiety had an increased K(m) (1.37-fold) and decreased K(cat) (0.79-fold). These
      indicate a 3.15-fold net increase and a 31% decrease in catalytic efficiency
      (K(cat)/K(m)) of the Glu and Xyl moieties. Activities and stabilities of both
      moieties at 40-90 degrees C or pH 3.0-10.0 were compared with those of the
      parental enzymes. Despite some variations, common optima were 40 degrees C and pH
      9.0 for the Glu moiety and parent, and 50-60 degrees C and pH 9.0 for the Xyl
      counterparts. Thus, the fusion enzyme Glu-Xyl was bifunctional, with greatly
      enhanced glucanase activity associated with a decrease in xylanase activity.

PMID- 16907725
TI  - IrvA-dependent and IrvA-independent pathways for mutacin gene regulation in
      Streptococcus mutans.
AB  - Streptococcus mutans is a primary pathogen associated with dental caries. Its
      bacteriocin (mutacin) production ability is thought to play an important role in
      maintaining competitiveness in the multispecies oral biofilm. Previous studies
      have demonstrated that the production of the lantibiotic, mutacin I, is
      responsive to multiple input signals and that a putative inducible repressor,
      irvA, seems to be involved in the luxS-mediated mutacin I gene regulation
      pathway. In this study, we demonstrate that these multiple inputs can be divided
      into two pathways: irvA-dependent and irvA-independent. Similar to luxS, signals
      mediated through vicK, pttB and hk03 exert their effect possibly through
      modulating irvA transcription, whereas signals mediated through ciaH, hrcA, adhE,
      and Smu1281 exert their effect through an unknown mechanism independent of irvA.

PMID- 16907726
TI  - Cellular location of polyamine transport protein PotD in Streptococcus
      pneumoniae.
AB  - Streptococcus pneumoniae encodes a transporter for polyamines that contributes to
      virulence in an animal model. The putative polyamine-binding protein, PotD, has
      an amino-terminal secretory peptide but no other domains known to be involved in
      anchoring proteins to the surface of Gram-positive bacteria. Cell fractionation
      and immunoblotting, along with flow cytometry, suggest that PotD is surface
      exposed and anchored to the cytoplasmic membrane by a potentially novel
      mechanism.

PMID- 16907727
TI  - Investigation of diarrhoeic faecal samples for enterotoxigenic, Shiga toxin
      producing and typical or atypical enteropathogenic Escherichia coli in Kashmir,
      India.
AB  - Three hundred and twenty-six Escherichia coli isolates recovered from 326 human
      faecal specimens from sporadic cases of diarrhoea in Kashmir valley, India, were
      investigated for the presence of stx(1), stx(2), eaeA, hlyA and lt virulence
      genes. None of the samples was positive for stx genes or Shiga toxins by PCR or
      enzyme-linked immunosorbent assay. Twenty-three E. coli isolates showed the
      presence of the eaeA gene, whereas three isolates harboured the lt gene.
      Enteropathogenic E. coli (EPEC) belonged to 10 different serogroups. Out of 23
      EPEC isolates, the majority (78.26%) were atypical while five (21.73%) were
      typical. Only one of the typical EPEC harboured the EAF plasmid. Subtyping of the
      eaeA gene showed the presence of eaeA-alpha(1), eaeA-beta, eaeA-xi and eaeA-eta
      in one, two, four and two isolates, respectively. None of the E. coli isolates
      possessed eaeA-delta, eaeA-epsilon and eaeA-zeta. This study further upholds the
      opinion that Shiga toxin-producing E. coli do not pose a major threat to human
      health in India and eaeA-alpha(1), eaeA-beta, eaeA-xi and eaeA-eta could be
      common EPEC subtypes prevalent in humans with diarrhoea in India. The present
      study appears to be the first report of subtype analysis of the eaeA gene from
      India and also records the isolation of EPEC with the eaeA-xi gene from humans.

PMID- 16907728
TI  - Small deletion variants of the replication protein, pi, and their potential for
      over-replication-based antimicrobial activity.
AB  - The emergence of multiply antibiotic-resistant microorganisms in the environment
      has become a serious public health threat. To address this, our lab has devised a
      methodology in which antimicrobial agents are transferred into unwanted cells
      using the process of bacterial conjugation. In the work described here, we
      pursued proteins that cause plasmid over-replication as potential antimicrobial
      agents. Our focus was on the pir-encoded pi protein of plasmid R6K that possesses
      both positive and negative functions in controlling gamma origin-based
      replication. We observed that three of four pir mutations examined, including two
      in-frame deletions, severely impaired negative plasmid-replication control. The
      resulting over-replication phenotype was particularly strong when a pir mutant
      was placed in cis to gamma origin. In conjugative mating experiments with several
      representatives of the family Enterobacteriaceae, the plasmids expressed
      postconjugational antimicrobial activity. The potential utility of a conjugation
      based antimicrobial approach is discussed. Additionally, we describe the
      replication inhibitory function of a novel and useful Rep protein variant,
      pi*M36A;M38A, which binds iteron DNA exclusively as dimers.

PMID- 16907729
TI  - Sequence and comparative genomic analysis of lactococcal bacteriophages jj50, 712
      and P008: evolutionary insights into the 936 phage species.
AB  - The complete genome sequences of three lactococcal 936-type bacteriophages, 712,
      jj50 and P008, were determined. Comparative genomic analysis of these phages with
      the previously sequenced 936-type phages, sk1 and bIL170, reveals a strict
      conservation of the overall genetic organization of this geographically diverse
      phage group. Genetic divergence was mainly observed in the early expressed region
      of the phage genomes, where a number of deletions, exchanges and insertions
      appear to have occurred. These genetic differences may be responsible for the
      observed differential sensitivity to the lactococcal DNA injection blocking
      protein, Sie(2009), and the abortive infection system, AbiA.

PMID- 16907730
TI  - Cloning, sequence analysis and heterologous expression of the Myrothecium
      gramineum orotidine-5'-monophosphate decarboxylase gene.
AB  - A 2918 bp sequence coding for the orotidine-5'-monophosphate decarboxylase enzyme
      (OMPD) was isolated from the genome of Myrothecium gramineum. This sequence was
      analysed and, remarkably, it is the first OMPD gene of a Sordariomycete that has
      an intron. The gene codes for an enzyme of 282 amino acids. The nucleotide
      sequence and the amino acid sequence were compared with fungal OMPD sequences.
      They show the highest similarity to OMPD genes and enzymes of Aspergillus sp.,
      Penicillium sp. and Cladosporium fulvum. The functionality of the gene as a
      selection marker was proven by complementation of the uracil auxotrophy of
      Aspergillus nidulans FGSC A722.

PMID- 16907731
TI  - Identification, cloning and characterization of cysK, the gene encoding O
      acetylserine (thiol)-lyase from Azospirillum brasilense, which is involved in
      tellurite resistance.
AB  - O-Acetylserine (thiol)-lyase (cysteine synthase) was purified from Azospirillum
      brasilense Sp7. After hydrolysis of the purified protein, amino acid sequences of
      five peptides were obtained, which permitted the cloning and sequencing of the
      cysK gene. The deduced amino acid sequence of cysteine synthase exhibited
      homology with several putative proteins from Alpha- and Gammaproteobacteria.
      Azospirillum brasilense Sp7 cysK exhibited 58% identity (72% similarity) with
      Escherichia coli K12 and Salmonella enterica serovar Typhimurium cysteine
      synthase proteins. An E. coli auxotroph lacking cysteine synthase loci could be
      complemented with A. brasilense Sp7 cysK. The 3.0-kb HindIII-EcoRI fragment
      bearing cysK contained two additional ORFs encoding a putative transcriptional
      regulator and dUTPase. Insertional disruption of the cysK gene did not produce a
      cysteine auxotroph, indicating that gene redundancy in the cysteine biosynthetic
      or other biosynthetic pathways exists in Azospirillum, as already described in
      other bacteria. Nitrogen fixation was not altered in the mutant strain as
      determined by acetylene reduction. However, this strain showed an eight-fold
      reduction in tellurite resistance as compared to the wild-type strain, which was
      only observed during growth in minimal medium. These data confirm earlier
      observations regarding the importance of cysteine metabolism in tellurite
      resistance.

PMID- 16907732
TI  - Mushrooms by magic: making connections between signal transduction and fruiting
      body development in the basidiomycete fungus Schizophyllum commune.
AB  - The basidiomycete fungus Schizophyllum commune has been utilised as a model
      system for examining the genetic regulation of sexual reproduction, a process
      that culminates in the production of mushrooms in this and many other related
      species. Recent studies have suggested that conserved elements of the cyclic AMP
      (cAMP) signalling pathway play a role in the control of mushroom development in
      S. commune. The small G-protein Ras also appears to impinge on the process,
      either by inputting into the cAMP pathway, or by acting in parallel. The
      molecular connections between nutrient sensing and mushroom development are now
      beginning to be examined.

PMID- 16907733
TI  - Growth inhibition of Candida species and Aspergillus fumigatus by statins.
AB  - Statins are a class of drugs widely used for lowering high cholesterol levels
      through their action on 3-hydroxy-3-methylglutaryl-CoA reductase, a key enzyme in
      the synthesis of cholesterol. We studied the effects of two major statins,
      simvastatin and atorvastatin, on five Candida species and Aspergillus fumigatus.
      The statins strongly inhibited the growth of all species, except Candida krusei.
      Supplementation of Candida albicans and A. fumigatus with ergosterol or
      cholesterol in aerobic culture led to substantial recovery from the inhibition by
      statins, suggesting specificity of statins for the mevalonate synthesis pathway.
      Our findings suggest that the statins could have utility as antifungal agents and
      that fungal colonization could be affected in those on statin therapy.

PMID- 16907734
TI  - Discovery of novel Streptococcus pneumoniae antigens by screening a whole-genome
      lambda-display library.
AB  - Streptococcus pneumoniae is a causative agent of otitis media, pneumonia,
      meningitis and sepsis in humans. For the development of effective vaccines able
      to prevent pneumococcal infection, characterization of bacterial antigens
      involved in host immune response is crucial. In order to identify pneumococcal
      proteins recognized by host antibody response, we created an S. pneumoniae D39
      genome library, displayed on lambda bacteriophage. The screening of such a
      library, with sera either from infected individuals or mice immunized with the S.
      pneumoniae D39 strain, allowed identification of phage clones carrying S.
      pneumoniae B-cell epitopes. Epitope-containing fragments within the families of
      the histidine-triad proteins (PhtE, PhtD), the choline-binding proteins (PspA,
      CbpD) and zinc metalloproteinase B (ZmpB) were identified. Moreover, library
      screening also allowed the isolation of phage clones carrying three distinct
      antigenic regions of a hypothetical pneumococcal protein, encoded by the ORF
      spr0075 in the R6 strain genome sequence. In this work, Spr0075 is first
      identified as an expressed S. pneumoniae gene product, having an antigenic
      function during infection.

PMID- 16907735
TI  - Asymptomatic bacteriuria Escherichia coli strains: adhesins, growth and
      competition.
AB  - Urinary tract infections (UTIs) affect millions of people each year. Escherichia
      coli is the most common organism associated with asymptomatic bacteriuria (ABU)
      in humans. Persons affected by ABU may carry a particular E. coli strain for
      extended periods of time without any symptoms. In contrast to uropathogenic E.
      coli (UPEC) that cause symptomatic UTI, very little is known about the mechanisms
      by which these strains colonize the urinary tract. Here, we have investigated the
      growth characteristics in human urine as well as adhesin repertoire of nine ABU
      strains; the ability of ABU strains to compete against the UPEC strain CFT073 was
      also studied. The different ABU strains displayed a wide variety of the measured
      characteristics. Half of the ABU strains displayed functional type 1 fimbriae
      while only one expressed functional P fimbriae. A good correlation between the
      growth rate of a particular strain and the survival of the strain in competition
      against CFT073 was observed. Our results support the notion that for strains with
      reduced capacity to express fimbriae, the ability to grow fast in human urine
      becomes crucial for colonization of the urinary tract.

PMID- 16907736
TI  - Bacterial extracellular DNA forming a defined network-like structure.
AB  - It is generally assumed that nucleic acids are localized inside of living cells
      and that their primary function is the storage of information. In contrast,
      extracellular DNA is mainly considered as a remnant of lysed cells. Here, we
      report the formation of extracellular bacterial DNA as a spatial structure. An
      aquatic bacterium, strain F8, was isolated, which produced a stable filamentous
      network of extracellular DNA. Different staining and enzymatic techniques
      confirmed that it was DNA. We were able to amplify the 16S rRNA gene from the
      extracellular DNA. Restriction endonuclease cleavage and randomly amplified
      polymorphic DNA analysis of extracellular and genomic DNAs revealed major
      similarities, but also some differences in both sequences. Our data demonstrate a
      new function and relevance for extracellular DNA.

PMID- 16907737
TI  - Use of a codon alteration strategy in a novel approach to cloning the
      Mycobacterium tuberculosis diaminopimelic acid epimerase.
AB  - Previous attempts to express the diaminopimelate epimerase gene dapF of
      Mycobacterium tuberculosis in Escherichia coli resulted in undetectable enzyme
      yields. We used silent mutation of the first 10 codons of the recombinant ORF in
      an attempt to reduce the formation of secondary structures that might occur near
      the 5' end of the mRNA and inhibit translation. This significantly increased the
      yield of the enzyme, which was purified and characterized biochemically. This
      strategy could be generally applied to other mycobacterial genes that are
      difficult to express hetero-specifically and here provided pure M. tuberculosis
      DapF, a good foundation for future research in antimycobacterial agents.

PMID- 16907738
TI  - Initial characterization of a bolA homologue from Pseudomonas fluorescens
      indicates different roles for BolA-like proteins in P. fluorescens and
      Escherichia coli.
AB  - The RpoS-regulated bolA gene in Escherichia coli is important for the decrease in
      cell size during stationary phase or sudden carbon starvation. A Pseudomonas
      fluorescens strain mutated in a gene with homology to bolA reduced its cell size
      upon carbon starvation, and RpoS had little effect on bolA expression. The mutant
      grew slower than the wild-type strain in minimal medium with L-serine as the sole
      nitrogen source, while growth rates were similar on a mixture of L-serine and L
      cysteine. Reverse transcriptase polymerase chain reaction analysis indicated that
      the bolA homologue is the second gene in an operon where the two next ORFs encode
      putative proteins with homology to sulphurtransferases and protein disulphide
      isomerases. Complementation of the mutant phenotypes was only obtained by
      plasmids encoding BolA as well as the above two proteins. Growth phenotypes and
      gene homologies suggest that BolA-like proteins have different functions in E.
      coli and Pseudomonas.

PMID- 16907739
TI  - Identification of genes involved in siderophore transport in Streptomyces
      coelicolor A3(2).
AB  - The potential iron siderophore transporter genes have been determined from the
      genome sequence of Streptomyces coelicolor A3(2). One of these gene clusters,
      cdtABC, was disrupted and characterized to determine its role in the uptake of
      the siderophores produced by S. coelicolor. Resistance to the siderophore-like
      antibiotics, salmycin and albomycin, was tested in the parent and cdtABC mutant,
      showing that the parent, but not the mutant, was sensitive to salmycin, while
      both were resistant to albomycin. Ferrioxamine competition assays against
      salmycin suggest that the uptake of salmycin is via a ferrioxamine transport
      system. However, Fe-55 ferrioxamine B uptake experiments did not reveal any
      difference between the parent and mutant. This suggests that CdtABC specifically
      transports salmycin, while ferrioxamine uptake maybe substituted by another
      transport system.

PMID- 16907740
TI  - Expression of the short fimbriae of Porphyromonas gingivalis is regulated in oral
      bacterial consortia.
AB  - The Mfa1 protein of Porphyromonas gingivalis is the structural subunit of the
      short fimbriae and mediates coadhesion between P. gingivalis and Streptococcus
      gordonii. We utilized a promoter-lacZ reporter construct to examine the
      regulation of mfa1 expression in consortia with common oral plaque bacteria.
      Promoter activity of mfa1 was inhibited by S. gordonii, Streptococcus sanguinis
      and Streptococcus mitis. In contrast, Streptococcus mutans, Streptococcus
      cristatus, Actinomyces naeslundii, Actinobacillus actinomycetemcomitans and
      Fusobacterium nucleatum did not affect mfa1 expression. Expression of SspA/B, the
      streptococcal receptor for Mfa1, was not required for regulation of mfa1 promoter
      activity. Proteinaceous molecule(s) in oral streptococci may be responsible for
      regulation of Mfa1 expression. Porphyromonas gingivalis is capable of detecting
      heterologous organisms, and responds to selected organisms by specific gene
      regulation.

PMID- 16907741
TI  - Unveiling electrotransformation of Moraxella catarrhalis as a process of natural
      transformation.
AB  - The human respiratory tract pathogen Moraxella catarrhalis is a naturally
      competent microorganism. However, electrotransformation has long been used to
      introduce foreign DNA into this organism. This study demonstrated that
      electrotransformants obtained with linear or circular nonreplicating plasmid DNA
      originated exclusively from natural transformation processes taking place during
      the recovery phase after the application of current. Only replicating plasmid DNA
      could be introduced into M. catarrhalis by electrotransformation, in a type IV
      pilus-independent manner. Electrotransformation with homologous genomic DNA
      indicated that restriction of double-stranded DNA was independent of type III
      restriction-methylation systems. Nontransformability of M. catarrhalis by
      electrotransformation was observed using double- as well as single-stranded DNA.
      In addition, the study showed that natural competence is a very constant feature
      of M. catarrhalis.

PMID- 16907742
TI  - Identification of acquired DNA in Neisseria lactamica.
AB  - Anomalous DNA (aDNA) in prokaryotic genomes, identified by its aberrant
      nucleotide composition, generally represents horizontally acquired DNA. Previous
      studies showed that frequent DNA transfer occurs between commensal Neisseriae and
      Neisseria meningitidis. Currently, it is unknown whether aDNA regions are also
      transferred between these species. The genome of Neisseria lactamica strain
      892586 was assessed by a strategy that enables the selective isolation of aDNA,
      using endonucleases with recognition sites that are overrepresented in aDNA. Of
      eight regions with aDNA, five displayed similarity to virulence-associated
      meningococcal sequences. Of three aDNA fragments with limited or no similarity to
      neisserial sequences, one encodes a novel putative autotransporter/adhesin. The
      remaining two fragments are adjacent in the N. lactamica genome, and encode a
      novel putative ATPase/subtilisin-like protease operon. A similar operon is
      present in the genomes of different respiratory tract pathogens. The
      identification of aDNA from N. lactamica with similarity to meningococcal aDNA
      shows that genetic exchange between the Neisseriae is not limited to the
      neisserial core genome. The discovery of aDNA in N. lactamica similar to a locus
      in other pathogens substantially expands the neisserial gene pool.

PMID- 16907743
TI  - The small MbtH-like protein encoded by an internal gene of the balhimycin
      biosynthetic gene cluster is not required for glycopeptide production.
AB  - The balhimycin biosynthetic gene cluster of the glycopeptide producer
      Amycolatopsis balhimycina includes a gene (orf1) with unknown function. orf1
      shows high similarity to the mbtH gene from Mycobacterium tuberculosis. In almost
      all nonribosomal peptide synthetase (NRPS) biosynthetic gene clusters, we could
      identify a small mbtH-like gene whose function in peptide biosynthesis is not
      known. The mbtH-like gene is always colocalized with the NRPS genes; however, it
      does not have a specific position in the gene cluster. In all glycopeptide
      biosynthetic gene clusters the orf1-like gene is always located downstream of the
      gene encoding the last module of the NRPS. We inactivated the orf1 gene in A.
      balhimycina by generating a deletion mutant. The balhimycin production is not
      affected in the orf1-deletion mutant and is indistinguishable from that of the
      wild type. For the first time, we show that the inactivation of an mbtH-like gene
      does not impair the biosynthesis of a nonribosomal peptide.

PMID- 16907744
TI  - Enhanced acid resistance of oral streptococci at lethal pH values associated with
      acid-tolerant catabolism and with ATP synthase activity.
AB  - Caries-causing oral bacteria such as Streptococcus mutans are protected by the
      actions of F-ATPases against acid damage in dental plaque acidified by glycolytic
      acid production or ingestion of acids foods and beverages. Catabolites such as
      glucose and sucrose were found to enhance the protection of S. mutans and also
      other oral lactic-acid bacteria against acid killing at lethal pH values as low
      as 2.5. Protection involved glycolysis with the production of lactate and ATP,
      which is a substrate for F-ATPases. ATP could also be produced by starved cells
      apparently through synthase activity of the F-ATPase associated with acid
      decline. Fluoride and the organic weak-acid indomethacin acted to diminish this
      protection, as did F-ATPase inhibitors such as dicyclohexylcarbodi-imide.
      Protection against acid killing involving catabolism and synthase activity is
      likely to be important for plaque cariogenicity.

PMID- 16907745
TI  - Biodegradation of benzo(a)pyrene by a newly isolated Fusarium sp.
AB  - Benzo(a)pyrene (BaP) is a five-ring polycyclic aromatic hydrocarbon produced by
      the incomplete combustion of organic materials. It is one of the priority
      pollutants listed by the US Environmental Protection Agency. This study describes
      a fungal isolate that is able to biodegrade benzo(a)pyrene. The filamentous
      fungus, isolated from leaves of Pterocarpus macrocarpus Kurz., was identified as
      a Fusarium sp. (strain E033). Fusarium sp. E033 was able to survive in the
      presence of benzo(a)pyrene concentrations up to 1.2 mM (300 mg L(-1)).
      Biodegradation experiments using 0.4 mM (100 mg L(-1)) benzo(a)pyrene
      demonstrated that Fusarium sp. E033 was able to degrade 65-70% of the initial
      benzo(a)pyrene provided, and two transformation products, a dihydroxy dihydro
      benzo(a)pyrene and a benzo(a)pyrene-quinone, were detected within 30 days of
      incubation at 32 degrees C. The factors affecting biodegradation efficiency were
      also investigated. While increasing aeration promoted better fungal growth and
      benzo(a)pyrene biodegradation, increasing the glucose concentration from 5 to 50
      mM had an adverse effect on biodegradation. Ethanol and methanol, provided at 5
      mM to increase benzo(a)pyrene water solubility, increased the fungal biomass
      yield but did not promote degradation. The Fusarium sp. E033 isolated in this
      study can tolerate and degrade relatively high concentrations of benzo(a)pyrene,
      suggesting its potential application in benzo(a)pyrene bioremediation.

PMID- 16907746
TI  - Butyrate- and propionate-degrading syntrophs from permanently cold marine
      sediments in Skan Bay, Alaska, and description of Algorimarina butyrica gen.
      nov., sp. nov.
AB  - Two anaerobic, psychrotolerant, syntrophic strains were enriched from permanently
      cold, shallow anoxic marine sediments in Skan Bay, Alaska. One strain, AK-B(T),
      oxidized butyrate syntrophically and was isolated in defined coculture with a
      H(2)-using methanogen or in a dixenic coculture that also contained an acetate
      scavenging methanogen. The other enrichment culture syntrophically oxidized
      propionate. The growth of these syntrophic cultures was very slow: approximately
      1 year for cocultures of strain AK-B(T) to form colonies and >1 year for the
      propionate-oxidizing enrichment to form colonies. Neither culture grew axenically
      when supplied with the catabolic substrates crotonate, pyruvate, malate, or
      sulfate plus butyrate or propionate. Strain AK-B(T) catabolized iso-butyrate in
      syntrophic coculture but did not catabolize valerate or caproate. Phylogenetic
      analyses of the 16S rRNA gene sequence suggested that strain AK-B(T) was only
      distantly related to cultivated sulfate-reducing bacteria, and that this strain
      represented a new genus. We propose Algorimarina butyrica, with strain AK-B(T)
      (=OCM 842(T)), as the type strain. This report is the first description of
      psychrotolerant as well as marine butyrate--and propionate-oxidizing syntrophic
      organisms.

PMID- 16907747
TI  - Bioconversion of ferulic acid to vanillic acid by Halomonas elongata isolated
      from table-olive fermentation.
AB  - Halomonas elongata strain Mar (=CCUG 52759) isolated from table-olive
      fermentation is the first halophilic bacterium to be shown to transform ferulic
      acid to vanillic acid under hypersaline conditions. During growth on ferulic
      acid, this strain was capable of promoting the formation of a significant amount
      of vanillic acid and trace quantities of vanillin. The products were confirmed by
      high-performance liquid chromatography and gas chromatography-mass spectrometry
      analyses. Based on the different metabolites identified, an oxidative side chain
      degradation pathway of ferulic acid bioconversion to vanillic acid was suggested.
      Phylogenetic analysis of 16S rRNA gene revealed that this isolated strain Mar was
      identified as H. elongata. To increase the formation of vanillic acid, a resting
      cell method using H. elongata strain Mar was performed. The optimal yield of
      vanillic acid (86%) was obtained after a 6 h reaction using 5 mM of ferulic acid
      and 4 g of dry weight of cells L(-1) pregrown on ferulic acid and harvested at
      the end of the exponential phase.

PMID- 16907748
TI  - Challenging Xanthomonas campestris with low levels of arsenic mediates cross
      protection against oxidant killing.
AB  - Xanthomonas encounters highly toxic reactive oxygen species (ROS) from many
      sources, such as those generated by plants against invading bacteria, other soil
      bacteria and from aerobic respiration. Thus, conditions that alter intracellular
      ROS levels such as exposure to toxic metalloids would have profound effects on
      bacterial physiology. Here, we report that exposure of Xanthomonas campestris pv.
      phaseoli (Xp) to low levels of arsenic induces physiological cross-protection
      against killing by H(2)O(2) and organic hydroperoxide but not a superoxide
      generator. Cross-protection against H(2)O(2) and organic hydroperoxide toxicity
      was due to increased expression of genes encoding major peroxide-metabolizing
      enzymes such as alkyl hydroperoxide reductase (AhpC), catalase (KatA) and organic
      hydroperoxide resistance protein (Ohr). Arsenic-induced protection against
      H(2)O(2) and organic hydroperoxide requires the peroxide stress response
      regulators, OxyR and OhrR, respectively. Moreover, analyses of double mutants of
      the major H(2)O(2) and organic hyproperoxide-scavenging enzymes, Xp ahpC katA and
      Xp ahpC ohr, respectively, suggested the existence of unidentified OxyR- and OhrR
      regulated genes that are involved in arsenic-induced resistance to H(2)O(2) and
      organic hyproperoxide killing in Xp. These arsenic-induced physiological
      alterations could play an important role in bacterial survival both in the soil
      environment and during plant-pathogen interactions.

PMID- 16907749
TI  - Carbon monoxide uptake kinetics in unamended and long-term nitrogen-amended
      temperate forest soils.
AB  - The effect of nitrogen (N) additions on the dynamics of carbon monoxide
      consumption in temperate forest soils is poorly understood. We measured soil CO
      profiles, potential rates of CO consumption and uptake kinetics in temperate
      hardwood and pine control plots and plots amended with 50 and 150 kg N ha-1 year
      1 for more than 15 years. Soil profiles of CO concentrations were above
      atmospheric levels in the high-N plots of both stands, suggesting that in these
      forest soils the balance between consumption and production may be shifted so
      that either production is increased or consumption decreased. Highest rates of CO
      consumption were measured in the organic horizon and decreased with soil depth.
      In the N-amended plots, CO consumption increased in all but one soil depth of the
      hardwood stand, but decreased in all soil depths of the pine stand. CO enzyme
      affinities increased with soil depth in the control plots. However, enzyme
      affinities in the most active soil depths (organic and 0-5 cm mineral) decreased
      in response to low levels of N in both stands. In the high-N plots, affinities
      dramatically-increased in the hardwood stand, but decreased in the organic
      horizon and increased slightly in the 0-5 cm mineral soil in the pine stand.
      These findings indicate that long-term N addition either by fertilization or
      deposition may alter the size, composition and/or physiology of the community of
      CO consumers so that their ability to act as a sink for atmospheric CO has
      changed. This change could have a substantial effect on the lifetime of
      greenhouse gases such as CH4 and therefore the future of Earth's climate.

PMID- 16907750
TI  - Seasonal dynamics and toxicity of Cylindrospermopsis raciborskii in Lake Guiers
      (Senegal, West Africa).
AB  - Cylindrospermopsis raciborskii is a toxic bloom-forming cyanobacterium that
      occurs at tropical and temperate latitudes. Despite several reports from Africa,
      no data were previously available about its dynamics or toxic potential there. We
      therefore carried out a 1-year survey of the dynamics of C. raciborskii in the
      main water reservoir in Senegal, Lake Guiers. Cylindrospermopsis raciborskii
      never formed a bloom in this lake during the period studied, but was dominant
      during the dry season. The only observed bloom-forming species was a diatom,
      Fragilaria sp., which displayed a seasonal pattern contrary to that exhibited by
      C. raciborskii. Principal component analysis applied to environmental and
      phytoplankton data showed that high C. raciborskii biomasses were mainly related
      to high temperature and water column stability. Tests for C. raciborskii species
      related toxicity and/or toxin synthesis were performed on 21 isolated clones. All
      the strains isolated tested negative in mouse toxicity bioassays, toxin analysis
      (MS/MS) and tests for known cylindrospermopsin genes (ps, pks). The limited
      number of isolates studied, and the occurrence of toxic and nontoxic clones in
      natural cyanobacterial populations, mean that we cannot conclude that there is no
      C. raciborskii-associated health risk in this drinking water reservoir.

PMID- 16907752
TI  - Ranking the magnitude of crop and farming system effects on soil microbial
      biomass and genetic structure of bacterial communities.
AB  - Biological soil characteristics such as microbial biomass, community structures,
      activities, and functions may provide important information on environmental and
      anthropogenic influences on agricultural soils. Diagnostic tools and detailed
      statistical approaches need to be developed for a reliable evaluation of these
      parameters, in order to allow classification and quantification of the magnitude
      of such effects. The DOK long-term agricultural field experiment was initiated in
      1978 in Switzerland for the evaluation of organic and conventional farming
      practices. It includes three representative Swiss farming systems with
      biodynamic, bio-organic and conventional fertilization and plant protection
      schemes along with minerally fertilized and unfertilized controls. Effects on
      microbial soil characteristics induced by the long-term management at two
      different stages in the crop rotation, i.e. winter wheat after potato or corn,
      were investigated by analyzing soil bacterial community structures using analysis
      of PCR-amplified rRNA genes by terminal restriction fragment length polymorphism
      and ribosomal intergenic spacer analysis. Application of farmyard manure
      consistently revealed the strongest influence on bacterial community structures
      and biomass contents. Effects of management and plant protection regimes occurred
      on an intermediate level, while the two stages in the crop rotation had a
      marginal influence that was not significant.

PMID- 16907751
TI  - Vertical migration of phototrophic bacterial populations in a hypersaline
      microbial mat from Salins-de-Giraud (Camargue, France).
AB  - The spatio-temporal distribution of phototrophic communities of the hypersaline
      photosynthetic Camarguc microbial mat (Salins-de-Giraud, France) was investigated
      over a diel cycle by combining microscopic and molecular approaches. Microcoleus
      chthonoplastes and Halomicronema excentricum, the dominant cyanobacteria of this
      oxyphotrophic community, were observed with confocal laser scanning microscopy to
      determine their biomass profiles. Both bacteria have similar vertical
      distributions, varying from a homogenous distribution through the mat during the
      night, to a specific localization in the upper oxic zone of 1.5 mm during the
      day. Terminal restriction fragment length polymorphism of PCR-amplified pufM gene
      fragments revealed three groups of anoxyphototrophic populations, which varied
      according to the two opposite periods of the diel cycle under study. They were
      either specifically detected in only one period, or homogenously distributed
      through the mat in all periods, or located in specific zones of the mat depending
      on the period considered. Oxygen concentrations, pH and biomass of the major
      filamentous cyanobacteria were the determinative factors in the distribution of
      these anoxyphototrophs across the mat. Thus, vertical migration, cell-cell
      aggregate formation and metabolic switches were the most evident defence of the
      photosynthetic populations against the adverse effects of sulfide and oxygen
      fluxes during a diel cycle.

PMID- 16907753
TI  - Phylogeny of arbuscular mycorrhizal fungi predicts community composition of
      symbiosis-associated bacteria.
AB  - Many physicochemical and biotic aspects of the soil environment determine the
      community composition of bacteria. In this study, we examined the effects of
      arbuscular mycorrhizal fungi, common symbionts of higher plants, on the
      composition of bacterial communities after long-term (7-8 years) enrichment
      culture in the presence of a plant host. We showed that the phylogeny of
      arbuscular mycorrhizal fungal isolates was a highly significant predictor of
      bacterial community composition, as assessed by cluster analysis, redundancy
      analysis and linear discriminant analysis of phospholipid fatty acid patterns.
      Numerous phospholipid fatty acids differed between the phylogenetic groupings;
      this pattern also held for fungal-origin phospholipid fatty acids and in a
      combined bacterial/fungal analysis, suggesting that categorizing phospholipid
      fatty acids into predominantly bacterial and fungal origin did not affect the
      overall outcome. The mechanisms underlying this observation could include
      substrate quality (and quantity) effects, interactions mediated by the host plant
      (e.g. rhizodeposition) and direct biotic interactions between arbuscular
      mycorrhizal fungi and bacterial populations. Our results suggest that aspects of
      arbuscular mycorrhizal fungal functions may be partially explained by the
      symbiosis-accompanying bacterial communities, a possibility that should be
      explicitly considered in studies examining the roles of arbuscular mycorrhizal
      fungal species diversity in soil and ecosystem processes.

PMID- 16907754
TI  - Cellulolytic and fermentative guilds in eutrophic soils of the Florida
      Everglades.
AB  - The northern Florida Everglades has been subject to eutrophication in recent
      years, resulting in well-documented changes in microbial ecology and a shift in
      the dominant plant species. This study investigated effects of plant quality and
      eutrophication on activities and composition of cellulolytic and fermentative
      guilds in soils. Most probable numbers of cellulolytic bacteria in eutrophic (F1)
      and transition (F4) soils were 10-fold higher than in oligotrophic soils (U3).
      Higher potential methanogenesis was observed from cellulose in microcosms with
      soils from F1 and F4, compared to U3 soils. Nutrient status of soil, rather than
      plant type, was the major factor controlling methanogenesis rates, although
      numbers of fermentative bacteria were higher in microcosms supplemented with
      ground cattail (dominant in F1 and F4) than with sawgrass (dominant component of
      soil in U3), regardless of soil origin. DNA sequence analysis indicated
      Clostridium assemblage composition correlates with soil nutrient status.

PMID- 16907755
TI  - Soil bacterial diversity in a loblolly pine plantation: influence of
      ectomycorrhizas and fertilization.
AB  - We studied the effect of ectomycorrhizas and fertilization on soil microbial
      communities associated with roots of 10-year-old loblolly pine. Ectomycorrhizas
      were identified using a combination of community terminal restriction fragment
      profiling and matching of individual terminal restriction fragments to those
      produced from ectomycorrhizal clones and sequences recovered from roots and
      sporocarps. Differences between bacterial communities were initially determined
      using cluster analysis on community terminal restriction fragment profiles and
      through subsequent recovery of 16S rDNA clones. Analysis of bacterial clones
      revealed that terminal restriction fragment length was often shared between
      taxonomically dissimilar bacterial types. Consequently, we could not reliably
      infer the identity of peaks in the bacterial community profile with some
      exceptions, notably chloroplast rDNA that generated an approximate peak size of
      80.2 bp. Fertilization increased the frequency of a Piloderma-like
      ectomycorrhiza. However, we did not detect clear effects of fertilization or the
      presence of viable ectomycorrhizas on bacterial communities. Bacterial
      communities seemed to be determined largely by the carbon and nitrogen content of
      soil. These results suggest that important soil microbial groups respond
      differently to soil conditions and management practices, with ectomycorrhizal
      communities reflecting past nutrient conditions and bacterial communities
      reflecting current environmental conditions of soil microsites.

PMID- 16907756
TI  - Eukaryotic diversity in historical soil samples.
AB  - The eukaryotic biodiversity in historical air-dried samples of Dutch agricultural
      soil has been assessed by random sequencing of an 18S rRNA gene library and by
      denaturing gradient gel electrophoresis. Representatives of nearly all taxa of
      eukaryotic soil microbes could be identified, demonstrating that it is possible
      to study eukaryotic microbiota in samples from soil archives that have been
      stored for more than 30 years at room temperature. In a pilot study, 41 sequences
      were retrieved that could be assigned to fungi and a variety of aerobic and
      anaerobic protists such as cercozoans, ciliates, xanthophytes (stramenopiles),
      heteroloboseans, and amoebozoans. A PCR-denaturing gradient gel electrophoresis
      analysis of samples collected between 1950 and 1975 revealed significant changes
      in the composition of the eukaryotic microbiota.

PMID- 16907757
TI  - Microbial diversity of cold-seep sediments in Sagami Bay, Japan, as determined by
      16S rRNA gene and lipid analyses.
AB  - Microbial communities in Calyptogena sediment and microbial mats of Sagami Bay,
      Japan, were characterized using 16S rRNA gene sequencing and lipid biomarker
      analysis. Characterization of 16S rRNA gene isolated from these samples suggested
      a predominance of bacterial phylotypes related to Gammaproteobacteria (57-64%)
      and Deltaproteobacteria (27-29%). The Epsilonproteobacteria commonly found in
      cold seeps and hydrothermal vents were only detected in the microbial mat sample.
      Significantly different archaeal phylotypes were found in Calyptogena sediment
      and microbial mats; the former contained only Crenarchaeota clones (100% of the
      total archaeal clones) and the latter exclusively Euryarchaeota clones, including
      the anaerobic oxidation of methane archaeal groups ANME-2a and ANME-2c. Many of
      these lineages are as yet uncultured and undescribed groups of bacteria and
      archaea. Phospholipid fatty acid analysis suggested the presence of sulphate
      reducing and sulphur-oxidizing bacteria. Results of intact glyceryl dialkyl
      glyceryl tetraether lipid analysis indicated the presence of nonthermophilic
      marine planktonic archaea. These results suggest that the microbial community in
      the Sagami Bay seep site is distinct from previously characterized cold-seep
      environments.

PMID- 16907758
TI  - Community composition and activity of prokaryotes associated to detrital
      particles in two contrasting lake ecosystems.
AB  - The composition, distribution and extracellular enzyme activities of bacteria
      attached to small (2-50 microm in size) transparent exopolymer and Coomassie
      stained proteinaceous particles (TEP and CSP) were examined in two lakes of
      different trophic status located in the Massif Central of France. TEP
      concentrations (10(4)-10(6) particle per L) were significantly higher in the more
      productive lake and were significantly related to chlorophyll a concentrations.
      The majority of TEP and CSP were colonized by bacteria that constituted 2.6% and
      7.4% of the total 4',6-diamidino-2-phenylindole-stained bacteria in lakes Pavin
      and Aydat, respectively. In both lakes, the composition of particle-associated
      bacteria was different from that of free-living bacteria, the Betaproteobacteria
      and Bacteroidetes (i.e. former Cytophaga-Flavobacteria group) being the dominant
      groups on particles. We also found that 2-5 microm TEP were more colonized than 2
      5 microm CSP in the two lakes, and that TEP colonization was higher in the less
      productive lake. Measurements of Leucine aminopeptidase and alpha-glucosidase
      activities in fractionated lake water (0.2-1.2, 1.2-5 and >5 microm fractions)
      indicated that proteolytic activity was always higher and that particle
      associated bacteria have higher enzymatic activities than free-living bacteria.
      The glycolytic activities in the 1.2-5 and >5 microm fractions were related to
      the abundance of TEP. We conclude that small freshwater detrital organic
      particles constitute microhabitats with high bacterial activities in pelagic
      environments and, undoubtedly, present significant ecological implications for
      the prokaryotic community structure and function in aquatic ecosystems.

PMID- 16907759
TI  - Uncultured Archaea in a hydrothermal microbial assemblage: phylogenetic diversity
      and characterization of a genome fragment from a euryarchaeote.
AB  - The polychaete Alvinella pompejana lives in organic tubes on the walls of active
      hydrothermal chimneys along the East Pacific Rise. To examine the diversity of
      the archaeal community associated with the polychaete tubes, we constructed
      libraries by direct PCR amplification and cloning of 16S rRNA genes. Almost half
      of the sequences of the 16S rRNA gene libraries clustered with uncultured
      archaeal groups. In an effort to access genomic information from uncultured
      archaeal members we further constructed a fosmid library from the same DNA
      source. One of the clones, Alv-FOS5, was sequenced completely. Its sequence
      analysis revealed an incomplete rRNA operon and 32 predicted ORFs. Seventeen of
      these ORFs have been assigned putative functions, including transcription and
      translation, cellular processes and signalling, transport systems and metabolic
      pathways. Phylogenetic analyses of the 16S rRNA gene suggested that Alv-FOS5
      formed a new lineage related to members of Deep-Sea Hydrothermal Vent
      Euryarchaeota group II. Phylogenetic analyses of predicted proteins revealed the
      existence of likely cases of horizontal gene transfer, both between Crenarchaeota
      and Euryarchaeota and between Archaea and Bacteria. This study is the first step
      in using genomics to reveal the physiology of an as yet uncultured group of
      archaea from deep-sea hydrothermal vents.

PMID- 16907761
TI  - Molecular analysis of lichen-associated bacterial communities.
AB  - The bacterial communities associated with 11 different lichen samples (belonging
      to eight different species) from different habitats were investigated. The
      culturable aerobic-heterotrophic fraction of the bacterial communities was
      isolated from nine lichen samples on protein-rich and sugar-rich/N-free media.
      Thirty-four bacterial isolates were purified and pooled into groups (phylotypes)
      by analysis of the ribosomal internal transcribed spacer polymorphism. Twenty
      five phylotypes were identified, each comprising between one and three isolates.
      One isolate of each phylotype was partially sequenced and the resulting 16S rRNA
      gene sequences were compared in a phylogenetic analysis. Three genera of
      Firmicutes, four of Actinobacteria and three of Proteobacteria were identified.
      Two phylotypes, belonging to the phyla Actinobacteria and Proteobacteria,
      respectively, were not identified at genus level. Some bacterial taxa were
      retrieved frequently in different lichen species sampled in the same or different
      sites. Paenibacillus and Burkholderia phylotypes seem to be common in lichens.
      Luteibactor rhizovicina was found in three different lichens of two different
      regions. In a cultivation-independent approach, total DNA was extracted from 11
      lichen samples. Molecular fingerprints of the bacterial communities were obtained
      by PCR-amplification of the internal transcribed spacer region, and sequencing of
      selected bands indicated the presence of additional bacteria.

PMID- 16907760
TI  - Endolithic photosynthetic communities within ancient and recent travertine
      deposits in Yellowstone National Park.
AB  - Molecular and culture based methods were used to survey endolithic,
      photosynthetic communities from hot spring-formed travertine rocks of various
      ages, ranging from<10 to greater than 300,000 years. Much of this travertine
      contained a 1-3-mm-thick greenish band composed mainly of cyanobacteria 1-5 mm
      below the rock surface. The travertine rocks experienced desiccation in summer
      and freezing in winter. A total of 83 environmental 16S rRNA gene sequences were
      obtained from clone libraries and denaturing gradient gel electrophoresis. Small
      subunit rRNA gene sequences and cell morphology were determined for 36
      cyanobacterial culture isolates from these samples. Phylogenetic analysis showed
      that the 16S rRNA gene sequences fell into 15 distinct clusters, including
      several novel lineages of cyanobacteria.

PMID- 16907762
TI  - An assessment of the hypervariable domains of the 16S rRNA genes for their value
      in determining microbial community diversity: the paradox of traditional
      ecological indices.
AB  - Amplicon length heterogeneity PCR (LH-PCR) was investigated for its ability to
      distinguish between microbial community patterns from the same soil type under
      different land management practices. Natural sagebrush and irrigated mouldboard
      ploughed soils from Idaho were queried as to which hypervariable domains, or
      combinations of 16S rRNA gene domains, were the best molecular markers. Using
      standard ecological indices to measure richness, diversity and evenness, the
      combination of three domains, V1, V3 and V1+V2, or the combined V1 and V3 domains
      were the markers that could best distinguish the undisturbed natural sagebrush
      communities from the mouldboard-ploughed microbial communities. Bray-Curtis
      similarity and multidimensional scaling were found to be better metrics to
      ordinate and cluster the LH-PCR community profiling data. The use/misuse of
      traditional ecological indices such as diversity and evenness to study microbial
      community profiles will remain a major point to consider when performing
      metagenomic studies.

PMID- 16907764
TI  - Bone tissue formation adjacent to implants placed in fresh extraction sockets: an
      experimental study in dogs.
AB  - OBJECTIVE: To study the healing of marginal defects that occurred at implants
      placed in a healed ridge or in fresh extraction sockets. MATERIAL AND METHODS:
      Six dogs were used. The right side of the mandible was used in the first part of
      the study. The first, second premolars and first molars were extracted. After 3
      months of healing the bone was prepared for implant installation in these
      premolar and molar sites. The marginal 5 mm of each recipient site was widened
      with a conical drill. Following implant installation a gap of varying dimension
      occurred around the titanium rod (artificial defect (A) sites). At this interval
      the third and fourth premolars were extracted and implants were installed in the
      distal socket of the two teeth (natural defect (N) sites). The flaps were sutured
      to allow non-submerged healing. After 2 months, the procedures were repeated in
      the left side. Two months later the animals were euthanized, and biopsies were
      obtained and prepared for histological examination. RESULTS: The length of the
      zone of de novo'bone-to-implant contact' in the defect region was longer at the A
      sites than at the N sites both at the 2- and the 4-month interval. Further, while
      after 4 months of healing the marginal bone crest at the A sites was located
      close to the abutment/fixture junction, at the N sites a marked reduction of the
      height of the bone crest was documented. Hence, most A site defects became
      completely resolved whereas healing of the N site defects was incomplete.
      CONCLUSION: The process of bone modeling and remodeling at an implant placed in a
      fresh extraction socket differs from the resolution of marginal defects that may
      occur following implant installation in a healed ridge.

PMID- 16907765
TI  - Horizontal ridge augmentation using autogenous block grafts and the guided bone
      regeneration technique with collagen membranes: a clinical study with 42
      patients.
AB  - OBJECTIVE: To analyze the clinical outcome of horizontal ridge augmentation using
      autogenous block grafts covered with an organic bovine bone mineral (ABBM) and a
      bioabsorbable collagen membrane. MATERIAL AND METHODS: In 42 patients with severe
      horizontal bone atrophy, a staged approach was chosen for implant placement
      following horizontal ridge augmentation. A block graft was harvested from the
      symphysis or retromolar area, and secured to the recipient site with fixation
      screws. The width of the ridge was measured before and after horizontal ridge
      augmentation. The block graft was subsequently covered with ABBM and a collagen
      membrane. Following a tension-free primary wound closure and a mean healing
      period of 5.8 months, the sites were re-entered, and the crest width was re
      assessed prior to implant placement. RESULTS: Fifty-eight sites were augmented,
      including 41 sites located in the anterior maxilla. The mean initial crest width
      measured 3.06 mm. At re-entry, the mean width of the ridge was 7.66 mm, with a
      calculated mean gain of horizontal bone thickness of 4.6 mm (range 2-7 mm). Only
      minor surface resorption of 0.36 mm was observed from augmentation to re-entry.
      CONCLUSIONS: The presented technique of ridge augmentation using autogenous block
      grafts with ABBM filler and collagen membrane coverage demonstrated successful
      horizontal ridge augmentation with high predictability. The surgical method has
      been further simplified by using a resorbable membrane. The hydrophilic membrane
      was easy to apply, and did not cause wound infection in the rare instance of
      membrane exposure.

PMID- 16907766
TI  - Comparison of early telescope loading of non-submerged ITI implants in irradiated
      and non-irradiated oral cancer patients.
AB  - OBJECTIVE: To compare early dental implant loading in irradiated and non
      irradiated oral cancer patients in order to accelerate masticatory function
      improvement and quality of life. PATIENTS AND METHODS: One hundred and fourteen
      non-submerged interforaminal ITI implants were early loaded in 30 patients after
      3 weeks in situ (telescoped overdenture). Nineteen patients received 72 implants
      (63%) after local irradiation; 11 non-irradiated patients received 42 implants
      (37%) with a 24-month follow-up. RESULTS: At 24 month follow-up, one early
      failure had occurred in an irradiated patient (=99% functioning implants in
      situ). Peri-implant bleeding and plaque index were similarly high in both groups
      (40 to 68% average). The Results of other measured parameters were as follows
      (values for mean; irradiated; non-irradiated patients with respective standard
      deviations; significance of comparison): bone loss (0.9+/-0.9; 1.4+/-0.9; 0.4+/
      0.5 mM; P<0.01); Periotest score (-2.7+/-2.7; -2.4+/-2.2; -3.1+/-3.3; P<0.2);
      gingival recession (0.6+/-0.7 mM; 0.8+/-0.9 mM; 0.4+/-0.5 mM, P<0.02); and peri
      implant probing depths (3+/-1.2; 2.6+/-0.6; 3.4+/-1.7 mM; P<0.002). CONCLUSION:
      The results suggest reliable non-submerged implantation and early loading.
      However, bone loss in irradiated mandibles, combined with higher average
      Periotest values and gingival recession in an oral environment of altered saliva
      quantity, quality, microflora and local scarring, requires extended follow-up.

PMID- 16907767
TI  - Peri-implant soft-tissue health surrounding cement- and screw-retained implant
      restorations: a multi-center, 3-year prospective study.
AB  - OBJECTIVE: The purpose of this prospective clinical study was to evaluate peri
      implant soft-tissue conditions and esthetic fulfillment during a 3-year follow-up
      period following prosthetic rehabilitation. MATERIAL AND METHODS: As part of a
      prospective multi-center study, 152 ITI dental implants were placed in 80
      patients in the maxillary anterior region. Fifty-nine crowns (38.82%) were cement
      retained, while 93 (61.18%) crowns were screw retained. At loading and 3, 6, 12
      and 36 months post-loading, modified plaque index (MPI), sulcus bleeding index
      (SBI), keratinized mucosa (KM), gingival level (GL), and esthetic fulfillment
      were recorded. RESULTS: All patients completed the study and no complications
      were reported. While statistically not significant at all time points, cement
      retained crowns seemed to present a worsening trend in MPI and SBI scores.
      Interestingly, screw-retained crowns seemed to present an opposite picture, their
      MPI and SBI scores improved over time. While plaque accumulation, prophylaxis and
      depth of crown margin significantly affected levels of sulcus bleeding,
      prophylaxis alone played a key role in reducing plaque accumulation. No soft
      tissue recession was observed in either cement- or screw-retained crowns up to 3
      years post-loading. Esthetic fulfillment survey revealed that patients did not
      have a preference for crown types; however, dentists favored cement-retained over
      screw-retained crowns. CONCLUSIONS: Peri-implant soft tissues responded more
      favorably to screw-retained crowns when compared with cement-retained crowns.
      However, no soft-tissue recession was observed in either type of crowns. Cement
      retained crowns were preferred by dentists, while patients were equally satisfied
      with either type of crowns they received.

PMID- 16907768
TI  - IL-1RN gene polymorphism is associated with peri-implantitis.
AB  - OBJECTIVES: Interleukin (IL)-1alpha, IL-1beta and their natural specific
      inhibitor IL-1 receptor antagonist (IL-1ra) play a key role in the regulation of
      the inflammatory response in periodontal tissues. Polymorphisms in the IL-1 gene
      cluster have been associated with severe adult periodontitis. We aimed to
      investigate the IL-1 gene cluster polymorphisms in patients with peri
      implantitis. MATERIAL AND METHODS: The study included 120 North Caucasian
      individuals. A total of 71 patients (mean age 68 years, 76% smokers)
      demonstrating peri-implantitis at one or more implants as evidenced by bleeding
      and/or pus on probing and bone loss amounting to >3 threads on Branemark implants
      and 49 controls (mean age 66 years, 45% smokers) with clinical healthy mucosa and
      no bone loss around the implants were recruited for the study. The titanium
      implants, ad modum Branemark, had been in function for at least 2 years.
      Mouthwash samples were collected and used for genotyping of the bi-allelic
      polymorphisms IL-1A(-889), IL-1B(+3953), IL-1B(-511) and a variable number of
      tandem repeat IL-1RN gene polymorphisms using PCR technique. RESULTS: Significant
      differences were found in the carriage rate of allele 2 in the IL-1RN gene
      between peri-implantitis patients and controls (56.5% vs. 33.3%, respectively;
      odds ratios (OR) 2.6; 95% confidence interval (CI) 1.2-5.6; P=0.015). Logistic
      regression analysis taking smoking, gender and age into account confirmed the
      association between the IL-1RN allele 2 carriers and peri-implantitis (OR 3; 95%
      CI 1.2-7.6; P=0.02). CONCLUSIONS: Our results provide evidence that IL-1RN gene
      polymorphism is associated with peri-implantitis and may represent a risk factor
      for this disease.

PMID- 16907769
TI  - Antimicrobial therapy using a local drug delivery system (Arestin) in the
      treatment of peri-implantitis. I: Microbiological outcomes.
AB  - OBJECTIVES: To assess the microbiological outcome of local administration of
      minocycline hydrochloride microspheres 1 mg (Arestin) in cases with peri
      implantitis and with a follow-up period of 12 months. MATERIAL AND METHODS: After
      debridement, and local administration of chlorhexidine gel, peri-implantitis
      cases were treated with local administration of minocycline microspheres
      (Arestin). The DNA-DNA checkerboard hybridization method was used to detect
      bacterial presence during the first 360 days of therapy. RESULTS: At Day 10,
      lower bacterial loads for 6/40 individual bacteria including Actinomyces
      gerensceriae (P<0.1), Actinomyces israelii (P<0.01), Actinomyces naeslundi type 1
      (P<0.01) and type 2 (P<0.03), Actinomyces odontolyticus (P<0.01), Porphyromonas
      gingivalis (P<0.01) and Treponema socranskii (P<0.01) were found. At Day 360 only
      the levels of Actinobacillus actinomycetemcomitans were lower than at baseline
      (mean difference: 1x10(5); SE difference: 0.34x10(5), 95% CI: 0.2x10(5) to
      1.2x10(5); P<0.03). Six implants were lost between Days 90 and 270. The
      microbiota was successfully controlled in 48%, and with definitive failures
      (implant loss and major increase in bacterial levels) in 32% of subjects.
      CONCLUSIONS: At study endpoint, the impact of Arestin on A. actinomycetemcomitans
      was greater than the impact on other pathogens. Up to Day 180 reductions in
      levels of Tannerella forsythia, P. gingivalis, and Treponema denticola were also
      found. Failures in treatment could not be associated with the presence of
      specific pathogens or by the total bacterial load at baseline. Statistical power
      analysis suggested that a case control study would require approximately 200
      subjects.

PMID- 16907770
TI  - Quality and quantity of bone following alveolar distraction osteogenesis in the
      human mandible.
AB  - PURPOSE: The purpose of this prospective study on humans were to evaluate (a) the
      clinical outcome of alveolar distraction osteogenesis for the correction of
      vertically deficient edentulous mandibular ridges, (b) the clinical outcome of
      dental implants placed in the distracted areas, and (c) the quality and quantity
      of the bone that had formed in the distraction gap. MATERIAL AND METHODS: Seven
      patients presenting vertically deficient edentulous ridges were treated by means
      of distraction osteogenesis with an intraoral alveolar distractor. Approximately
      3 months after consolidation of the distracted segments, 20 ITI solid screw SLA
      implants were placed in the distracted areas. Three to 4 months later, abutments
      were connected and prosthetic loading of the implants started. During implant
      site preparation, bone biopsies were taken at the implant sites with trephine
      burrs for histologic and histometric analyses. RESULTS: The mean follow-up after
      the initial prosthetic loading was 18 months (range 12-24 months). The mean bone
      gain obtained at the end of distraction was 7 mm (range 5-9 mm). The cumulative
      success rate of implants 2 years after the onset of prosthetic loading was 95%,
      whereas the survival rate of implants was 100%. The newly formed bone consisted
      of woven bone reinforced by parallel-fibered bone with bone marrow spaces between
      the bone trabeculae. The bone area fraction in the distraction region ranged from
      21.6% to 57.8% (38.5+/-11.7%). DISCUSSION AND CONCLUSIONS: Results from this
      study showed that (a) distraction osteogenesis is a reliable technique for the
      correction of vertically deficient edentulous ridges, (b) the regenerated bone
      withstood the functional demands of implant loading, (c) survival and success
      rates of implants placed in the distracted areas were consistent with those of
      implants placed in native bone, and (d) there is sufficient bone volume and
      maturity in the distracted region for primary stability of the implant.

PMID- 16907771
TI  - Angiogenesis pattern of native and cross-linked collagen membranes: an
      immunohistochemical study in the rat.
AB  - The aim of the present study was to immunohistochemically evaluate angiogenesis
      pattern of native and cross-linked collagen membranes after subcutaneous
      implantation in rats. Five commercially available and three experimental
      membranes (VN) were included: (1) BioGide (BG), (2) BioMend (BM), (3) BioMend
      Extend (BME), (4) Ossix (OS), (5) TutoDent (TD), and (6-8) VN(1-3). Specimens
      were randomly allocated in unconnected subcutaneous pouches (n=4) separated
      surgically on the back of 40 wistar rats, which were divided into five groups (2,
      4, 8, 16, and 24 weeks), including eight animals each. Pattern of angiogenesis
      was labelled using primary mouse monoclonal antibody to transglutaminase II. For
      each membrane, the period of time, needed for a complete and homogeneous
      transmembraneous vascularization, was assessed immunohistomorhometrically.
      Differences between the membranes were found regarding the initial pattern of
      transmembraneous angiogenesis, as evaluated 2 weeks following implantation. Mean
      cross- and longitudinal-sectional area of blood vessels (%) was highest for VN(3)
      (5.27+/-2.73), followed by BG (2.45+/-0.88), VN(1) (2.07+/-0.29), VN(2) (1.91+/
      0.55), TD (1.44+/-0.53), BME (0.35+/-0.29) and BM (0.25+/-0.4). In contrast to BG
      and VN(1-3), BM, BME and TD exhibited a homogeneous transmembraneous formation of
      blood vessels merely 4-8 weeks following implantation. OS, however, exhibited no
      signs of angiogenesis throughout the whole study period. Within the limits of the
      present study, it may be concluded that pattern of transmembraneous angiogenesis
      markedly differs among the membranes investigated.

PMID- 16907772
TI  - Formation of new bone during vertical distraction osteogenesis of the human
      mandible is related to the presence of blood vessels.
AB  - We examined the effect of distraction rate on blood vessel growth in
      intramembraneous ossification after vertical distraction osteogenesis in the
      human mandible. Six edentulous patients (aged 60+/-9 years) with a severely
      atrophic mandible underwent bone augmentation with distraction osteogenesis. Two
      distraction rates (0.5 and 1 mm/day) were compared and for each group three
      patients were analyzed. Vascular histomorphometry was carried out in two
      different areas in the distraction gap: (1) in the first and (2) in the second 1
      mm area from the osteotomy line, representing the oldest and younger new-bone
      area, respectively. Correlation analysis was performed between blood vessel
      parameters and the amount of new bone formed during distraction. Histological
      analysis demonstrated the presence of blood vessels throughout the soft
      connective tissue in the distraction gap. The volume density of blood vessels
      between the two investigated areas was significantly lower in the 1 mm/day
      groups, suggesting a delay in angiogenesis in this group of patients. A positive
      correlation between blood vessel volume and bone volume density was found in the
      younger new-bone area but not in the oldest new-bone area. This correlation was
      due to a higher number of blood vessels rather than to a larger size of the blood
      vessels. Our data suggest that the lower blood vessel density found in the
      patients with 1 mm/day distraction rate may be related to disruption of
      angiogenesis in the soft connective tissue of the gap or to a less optimal
      mechanical stimulation of cells involved in angiogenesis. This probably results
      in the slower rate of osteogenesis seen at the 1 mm/day distraction rate compared
      with the 0.5 mm/day distraction rate. The data support the concept that a
      positive relationship exists between the density of blood vessels and the
      formation of bone. For distraction of the human mandible in elderly patients, a
      distraction rate of 0.5 mm/day seems beneficial.

PMID- 16907773
TI  - Vertical distraction osteogenesis in the human mandible: a prospective
      morphometric study.
AB  - Vertical distraction osteogenesis has received considerable interest as a way to
      augment bone prior to implant placement. However, very little is known regarding
      the appropriate distraction protocols in the human mandible. In this study, we
      evaluate the effect of the distraction rate and the duration of neutrofixation on
      bone formation and closure of the gap in the human mandible. Vertical distraction
      was performed in the atrophic mandible of 16 edentulous patients, aged 62+/-6
      years. The bone was distracted for approximately 10 mm at a rate of either 0.5 or
      1 mm/day. Bone biopsies were taken after 7-20 weeks of neutrofixation.
      Histological analysis demonstrated newly formed bone in the distraction gap in
      all biopsies. The bone was predominantly of the woven type. After 10 weeks of
      neutrofixation, the gap was bridged by new bone in two out of three intact
      samples in the 0.5 mm/day group, but not in two intact samples of the 1 mm/day
      group. Histomorphometry revealed longer bone trabeculae (P=0.02) and a somewhat
      increased bone volume in the area where new bone formation started (P=0.07) in
      the group of patients having the 0.5 mm/day of distraction rate than in the 1
      mm/day group. We conclude that in elderly patients, a distraction rate of 0.5
      mm/day results in faster osteogenesis in the distraction gap than a rate of 1
      mm/day. A minimum of 10 weeks of neutrofixation seems to be needed to close a 10
      mm gap after cessation of distraction.

PMID- 16907774
TI  - Evaluation of an in situ formed synthetic hydrogel as a biodegradable membrane
      for guided bone regeneration.
AB  - The aim of the present study was to test whether or not the application of an in
      situ formed synthetic hydrogel made of polyethylene glycol (PEG) used as a
      biodegradable membrane for guided bone regeneration will result in the same
      amount of bone regeneration as with the use of an expanded polytetrafluoro
      ethylene (ePTFE) membrane. In eight New Zealand White rabbits, four evenly
      distributed 6 mm diameter defects were drilled into the calvarial bone. Three
      treatment modalities were evenly distributed among the 32 defects: hydroxyapatite
      (HA)/tricalciumphosphate (TCP) granules covered at the outer and inner surface
      with a PEG membrane (test), HA/TCP granules covered at the outer and inner
      surface with an ePTFE membrane (positive control) and HA/TCP granules alone
      without membranes (negative control). After 4 weeks, the animals were sacrificed
      and the calvarial bones were removed. The area fraction of newly formed bone was
      determined by histomorphometrical analysis of the vertical sections from the
      middle of the defect and by micro-computed tomography of the entire defect.
      Multiple regression analysis (SAS GLM) was used to model the amount of new bone
      formation. The quantitative histomorphometric analysis clearly revealed higher
      values of newly formed bone for the two membrane groups compared with the
      negative control group. The average area fractions of newly formed bone measured
      within the former defect amounted to 20.3+/-9.5% for the PEG membrane, 18.9+/
      9.9% for the ePTFE membrane, and 7.3+/-5.3% for the sites with no membrane. The
      micro-computed tomography also showed higher values of new bone formation for the
      PEG and for the ePTFE groups compared with the negative control group. The GLM
      revealed a highly significant effect of the treatment on the amount of bone
      formation (P=0.0048). The values for the negative control group were
      significantly lower than the ones found in the PEG membrane group (P=0.0017),
      whereas the ePTFE membrane group showed no significant difference from the PEG
      membrane group. It is concluded that the PEG membrane can be used successfully as
      a biodegradable barrier membrane in the treatment of non-critical-size defects in
      the rabbit skull, and leads to similar amounts of bone regeneration as an ePTFE
      membrane.

PMID- 16907775
TI  - The effect of enamel matrix proteins and deproteinized bovine bone mineral on
      heterotopic bone formation.
AB  - To evaluate the osteoinductive potential of deproteinized bovine bone mineral
      (DBBM) and an enamel matrix derivative (EMD) in the muscle of rats. Sixteen rats
      were used in this study. The animals were divided in three groups. Group A: a
      pouch was created in one of the pectoralis profundis muscles of the thorax of the
      rats and DBBM particles (Bio-Oss) were placed into the pouch. Healing: 60 days.
      Group B: a small pouch was created on both pectoralis profundis muscles at each
      side of the thorax midline. In one side, a mixture of EMD (Emdogain) mixed with
      DBBM was placed into one of the pouches, whereas in the contralateral side of the
      thorax the pouch was implanted with DBBM mixed with the propylene glycol alginate
      (PGA--carrier for enamel matrix proteins of EMD). Healing: 60 days. Group C: the
      same procedure as group B, but with a healing period of 120 days. Qualitative
      histological analysis of the results was performed. At 60 days, the histological
      appearance of the DBBM particles implanted alone was similar to that of the
      particles implanted together with EMD or PGA at both 60 and 120 days. The DBBM
      particles were encapsulated into a connective tissue stroma and an inflammatory
      infiltrate. At 120 days, the DBBM particles implanted together with EMD or PGA
      exhibited the presence of resorption lacunae in some cases. Intramuscular bone
      formation was not encountered in any group. The implantation of DBBM particles
      alone, combined with EMD or its carrier (PGA) failed to exhibit extraskeletal,
      bone-inductive properties.

PMID- 16907777
TI  - Ninety percent success in palatal implants loaded 1 week after placement: a
      clinical evaluation by resonance frequency analysis.
AB  - To investigate the behaviour of early loaded palatal implants when observed with
      resonance frequency analysis (RFA). Twenty patients (seven males and 13 females,
      mean age 26.4 years) received one palatal implant each (length: 4 mm, diameter:
      3.3 mm; Orthosystem) for maximum orthodontic anchorage. The implants' stability
      was observed by RFA. Measurements were carried out at the time of surgery, after
      first orthodontic loading and subsequently once a week over a period of 12 weeks.
      Two palatal implants were lost. The other 18 remained stable. The average period
      from insertion to first loading was 6.7+/-0.8 days. The mean orthodontic force
      applied was 272.2+/-73.2 cN. The implant stability quotient (ISQ) value at the
      time of surgery averaged 69.4+/-3.9. The mean ISQ value 6.7 days after insertion
      was 69.8+/-3.6. Twelve weeks post-surgery the mean ISQ value was 69.8+/-3.5. A
      statistically significant decrease in stability was observed after 2 and 3 weeks
      post-surgery (P=0.005 and 0.04). The behaviour of early loaded palatal implants
      showed an initial decrease of the ISQ values. From 6 weeks post-surgery onward
      the ISQ values increased. Within the limitations of this study, the results
      suggest that the healing time of palatal implants reported in the literature (12
      weeks) should be discussed. An orthodontic loading of palatal implants 6 weeks
      post-surgery with a force up to 400 cN seems to be justified. Yet further
      investigations are necessary to evaluate the behaviour of early loaded palatal
      implants considering observation periods of over 12 weeks.

PMID- 16907776
TI  - Biodegradable polylactide membranes for bone defect coverage: biocompatibility
      testing, radiological and histological evaluation in a sheep model.
AB  - Large bony defects often show a delayed healing and have an increasing risk of
      infection. Several materials are used for the coverage of large defects. These
      materials must be biocompatible, easy to use, and must have an appropriate
      stability to present a mechanical hindrance. Aim of this study was to investigate
      two different biodegradable membranes for defect coverage in a sheep model. Round
      cranial defects (1.5 cm diameter) were created in sheep. Six different treatments
      were investigated: defects without membrane, defects covered with a poly(D,L
      lactide) or with a 70/30 poly(L/D,L-lactide) membrane and all defects with or
      without spongiosa filling. The sheep were sacrificed 12 or 24 weeks
      postoperatively. Bone formation in the defects was quantified by computer
      assisted measurements of the area of the residual defect on CT radiographs.
      Histomorphometry and host-tissue response were evaluated by light microscopy. The
      biocompatibility was investigated by analyzing the amount of osteoclasts and
      foreign body cells. Both membranes served as a mechanical hindrance to prevent
      the prolapse of soft tissue into the defect. The biocompatibility test revealed
      no differences in the amount and distribution of osteoclasts at the two
      investigated time points and between the investigated groups. No negative effect
      on the tissue regeneration was detectable between the investigated groups related
      to the type of membrane, but a foreign body reaction around the two membrane
      types was observed. In the membrane-covered defects, the spongiosa showed a
      progressing remodeling to the native bony structure of the cranium. The groups
      without spongiosa partly revealed new bone formation, without complete bridging
      in any group or at any time point. Comparing the 12 and 24 weeks groups, an
      increased bone formation was detectable at the later time point. In conclusion,
      the results of the present in vivo study reveal a good biocompatibility and
      prevention of soft tissue prolapse of the two used membranes without differences
      between the membranes. An enhanced remodeling of the spongiosa into native bony
      structures under the membranes was detectable, but no osteopromoting effect was
      observed due to the membranes.

PMID- 16907778
TI  - Does rotational strain at screw tightening affect the attainment or maintenance
      of osseointegration?
AB  - OBJECTIVES: This study investigated whether rotational strain affects
      osseointegration. MATERIAL AND METHODS: A total of 135 male rats were divided
      into five groups: 2-w rotation, 4-w rotation, 8-w rotation, 12-w rotation and
      control. Two hundred and seventy implants were inserted in rat tibia. The control
      group received no strain, while the 2-w, 4-w, 8-w and 12-w rotation groups
      received rotational strain at 2, 4, 8 and 12 weeks after implant placement,
      respectively. Removal torque (N cm) was measured in vivo. Bone contact rate (%)
      was calculated histomorphologically. Immunostaining for osteonectin (ON),
      osteopontin (OPN) and osteocalcin (OCN) was performed. The removal torque and
      bone contact rate were analyzed using one-way analyses of variance and the
      Scheffe method. RESULTS: At 4 weeks, the torque was significantly higher in the 2
      w rotation group (1.30+/-0.44 N cm) than in the control group (0.79+/-0.67 N cm).
      From 8 to 16 weeks, the strained groups showed no significant differences from
      the control group. From the bone contact rates, bone formation was larger in the
      4-week rotation group (62.9+/-10.7%) than in the control group (42.1+/-17.9%) at
      8 weeks. The 4-week rotation group showed higher bone contact rate (61.1+/-11.3%)
      compared with the other strained groups and maintained this higher value until 16
      weeks, showing no significant difference from the control group (72+/-5.2%). At
      the implant-bone interface, OPN was widely distributed and OCN was detected at a
      low level; however, ON could not be observed in any group. CONCLUSIONS: The bone
      contact rate changed when rotational strain was exerted at different periods
      after implant placement. However, the removal torque and distribution of
      extracellular matrix proteins were not adversely affected by the rotational
      strain.

PMID- 16907779
TI  - Early implant failure. Prognostic capacity of Periotest: retrospective study of a
      large sample.
AB  - OBJECTIVES: The objectives of this study were to determine the accuracy of
      Periotest to monitor primary implant stability at first-stage surgery, to
      identify by multivariate analysis the variables associated with early implant
      failure and to compare Periotest with radiographic study in the diagnosis of
      implant stability at second-stage surgery (during osseointegration period).
      MATERIAL AND METHODS: A 10-year retrospective study was conducted on 1084
      Branemark implants placed in 316 patients. Clinical variables, implant diameter
      and length, Periotest values (PTVs) and radiological variables were analyzed in
      bivariate and multivariate studies in order to determine their influence on early
      implant failure. RESULTS: After examination of the sensitivity and specificity
      values obtained for different PTV cutoff points, a cutoff PTV of -2 was selected
      (84% sensitivity and 39% specificity). In the bivariate analysis, early failure
      was significantly related to smoking habits, implant location, bone type, implant
      features and PTVs (-2 and >or=-2). In the final multiple logistic model, only age
      (odds ratio (OR)=4.53; 95% confidence interval (CI), 1.34-15.27), smoking habits
      (OR=2.5; 95% CI, 1.3-4.79), bone type (OR=1.93; 95% CI, 1.01-3.7) and PTV at
      first surgery (OR=3.01; 95% CI, 1.5-6.02) were independently related to early
      failure. CONCLUSIONS: The Periotest (with -2 cutoff) at first surgery offers high
      sensitivity in the prognosis of early implant loss and shows a greater capacity
      to evaluate stability during the osseointegration period compared with
      radiographic study.

PMID- 16907780
TI  - Biomechanical aspects of initial intraosseous stability and implant design: a
      quantitative micro-morphometric analysis.
AB  - PURPOSE: The objective of this biomechanical study was to explore the effect of
      bone micro-morphology on initial intraosseous stability of implants with
      different designs. MATERIAL AND METHODS: Straumann and Astra Tech dental implants
      were placed into anterior and posterior regions of completely edentulous maxilla
      and mandible of a human cadaver. Experiments were undertaken to quantify initial
      implant stability and bone micro-morphology. Installation torque values (ITVs)
      and implant stability quotients (ISQs) were measured to determine initial
      intraosseous implant stability. For quantification of relative bone volume and
      micro-architecture, sectioned implant-bone and bone core specimens of each
      implant placement site were consecutively scanned and trabecular bone was
      analyzed in a micro-computed tomography (micro-CT) unit. Experimental outcomes
      were evaluated for correlations among implant designs, initial intraosseous
      implant stability and bone micro-structural parameters. RESULTS: ITVs correlated
      higher with bone volume fraction (BV/TV) than ISQs, at 88.1% and 68.9% levels,
      respectively. Correlations between ITVs and micro-morphometric parameters were
      significant at the 95% confidence level (P<0.05) while ISQs were not. Differences
      in ITVs, ISQs and BV/TV data in regards to implant designs used were not
      significant at the 95% confidence level (P>0.05). CONCLUSION: Bone micro
      morphology has a prevailing effect over implant design on intraosseus initial
      implant stability, and ITV is more sensitive in terms of revealing biomechanical
      properties at the bone-implant interface in comparison with ISQ.

PMID- 16907781
TI  - Influence of smoking on osseointegrated implant failure: a meta-analysis.
AB  - The aim of this study was to examine the influence of smoking on osseointegrated
      implant failure by performing a meta-analysis. A computerized literature search
      using PubMed database (in English) and Japana Centra Revuo Medicina (in Japanese)
      was carried out to identify all relevant studies. Among 175 studies identified
      and chosen for detailed review, 19 were appropriate for inclusion in our meta
      analysis. When smokers were compared with non-smokers, odds ratio (OR) for
      osseointegrated implant failure was significantly elevated (OR 2.17, 95%
      confidence intervals (CI), 1.67-2.83). Seven studies were appropriate to examine
      the influence of intra-oral location (maxillary arch vs. mandibular arch) of
      implant failure on smoking. The OR for implant failure occurring in the maxillary
      arch was significantly elevated (OR 2.06, 95% CI, 1.61-2.65), whereas the OR in
      the mandibular arch did not demonstrate a significant increased risk associated
      with smoking (OR 1.32, 95% CI, 0.72-2.4). Our meta-analysis revealed a
      significant relationship between smoking and the risk of osseointegrated implant
      failure, more particularly those implants located in the maxillary arch.

PMID- 16907783
TI  - The relevance of scholarship for nursing research and practice. 1999.

PMID- 16907784
TI  - From scholarship to action and innovation.

PMID- 16907786
TI  - Living with chronic obstructive pulmonary disease: insiders' perspectives.
AB  - AIM: This paper reports a study of the experiences of older adults with severe
      chronic obstructive pulmonary disease, with the aim of gaining an understanding
      of how the disease had affected their lives. BACKGROUND: Chronic obstructive
      pulmonary disease is a major personal and public health burden and is the fifth
      cause of mortality worldwide. The brief encounters that healthcare professionals
      have with patients in hospitals, physicians' offices and other outpatient
      settings are insufficient to be able to truly understand the challenges that
      people face in the attempt to integrate a chronic illness into their lives.
      Previous qualitative studies on chronic obstructive pulmonary disease have tended
      to focus on specific problems associated with the disease, such as fatigue and
      social isolation. METHOD: A hermeneutic phenomenological study was carried out
      with 10 older adults who participated in a local hospital's case management or
      pulmonary rehabilitation programme. Data were collected by interviews in 2003.
      FINDINGS: Three major themes were identified: Knowing What Works, Hanging
      On...Barely, and Losing Control-Gaining Control. The changes associated with
      chronic obstructive pulmonary disease were described as increasingly challenging
      and even threatening to participants' current lifestyles. The impact of dyspnoea
      was great and invaded almost every aspect of their lives. Participants identified
      the most effective methods to resolve shortness of breath. CONCLUSION: People
      with severe chronic obstructive pulmonary disease have had extensive experience
      of managing their disease and are familiar with techniques that have helped them
      integrate the illness and symptoms into their lives. Nurses can synthesize
      patient knowledge with nursing knowledge to assist patients with severe chronic
      obstructive pulmonary disease to achieve their maximum quality of life.

PMID- 16907787
TI  - Male nurses' experiences of providing intimate care for women clients.
AB  - AIM: This paper reports a study of male nurses' experiences of providing intimate
      care for women clients. BACKGROUND: The number of men entering the nursing
      profession has increased worldwide. As a consequence of the move to a more gender
      balanced profession, debate has ensued over how intimate care should be performed
      when this requires male nurses to be physically close to women clients. As there
      was little previous work on this topic, we wished to provide nurses, clients and
      other healthcare professionals with a better understanding of male nurses'
      experiences of working with women clients and within a healthcare system where
      they often feel excluded. METHOD: Semi-structured, open-ended interviews were
      conducted with male nurses working in various clinical settings in Western
      Australia. Latent content analysis was used to analyse the interviews, which were
      carried out between June and July 2004. FINDINGS: Three themes were identified:
      the definition of intimate care, the emotional experience associated with
      providing intimate care and strategies used to assist in the delivery of intimate
      care for women clients. Providing intimate care for women clients was a
      challenging experience for male nurses. Participants described how it required
      them to invade these clients' personal space. Consequently, they often
      experienced various negative feelings and used several strategies to assist them
      during care delivery. CONCLUSIONS: Nurse educators should assist male nurses to
      be better prepared to interact with women clients in various settings.
      Furthermore, workplace environments need to provide additional support and
      guidance for male nurses to enable them to develop effective coping strategies to
      manage challenging situations.

PMID- 16907788
TI  - Nurses' opportunistic interventions with patients in relation to smoking.
AB  - AIM: This paper reports a study exploring nurses' provision of opportunistic
      health education on smoking for hospital patients. BACKGROUND: Smoking cessation
      guidelines recommend assessment of patients' smoking habits and provision of
      smoking cessation advice when possible, and highlight the importance of the role
      of nurses in health promotion and health education. In the past, nurses have been
      criticized for lack of knowledge, skills and confidence in relation to health
      education and the perception that it is additional to, rather than integrated
      with, nursing care. METHODS: A qualitative case study design was selected to
      explore the health education practice of 12 nurses working in acute wards in
      three general hospitals in Scotland. Data were collected in 2000 through non
      participant observation, semi-structured interviews and the use of a radio
      microphone to record nurse-patient interactions. The data analysis was guided by
      four key elements of health education practice: 'the teachable moment',
      'readiness to learn', 'the provision of health information' and 'oral
      communication'. FINDINGS: Smoking was part of the nurses' agenda, as most
      recognized opportunities to introduce health education on smoking during nursing
      care, suggesting a tentative move towards the integration of health education
      with nursing care. Evidence from patients' interactions indicated ample
      opportunity for nurses to provide smoking-related health information. However,
      the content of nurses' interactions on smoking was variable, with some limited by
      poor communication skills and inadequate knowledge of smoking and smoking
      cessation. The context of the interactions was also important in understanding
      some of the restrictions on conversational progress. CONCLUSIONS: Nurses require
      the knowledge and skills to perform a health education role, and the inclusion of
      smoking cessation guidelines in nursing curricula would contribute to this. Where
      patients are in hospitals for short periods of time, opportunistic health
      education on smoking needs to be introduced as the basis for more specialist
      intervention.

PMID- 16907789
TI  - Spectators & spectacles: nurses, midwives and visuality.
AB  - AIM: In this paper we reflect on how linear perspective vision influences the
      practice of nurses and midwives and to advance understanding of clinical practice
      in technologically intensive environments through examination of drawings by
      nurses and midwives and through critical analysis. BACKGROUND: There is
      increasing emphasis on vision in Western culture, and both nurses and midwives
      spend a great deal of time observing their clinical environment(s). Healthcare
      practitioners work increasingly in image-based realities and nurses rely on
      visual skills. Vision and visual representation are central to our practice and
      are important to examine because we look often at technology to assess people and
      care. DISCUSSION: The world in which we practise is one of meaning(s).
      Technological development is transformative in nature and produces changes that
      alter the way(s) we give care. Amongst all this change, it is unclear how we
      practise in environments characterized by increasing technology and it is unknown
      how nursing and midwifery practice alter as a result. CONCLUSION: Simple drawings
      included in this paper highlight an important and shared experience of clinical
      practice(s). They emphasize the importance and scope of the visual sense and
      expose practitioner behaviour that has enormous implications for current and
      future professional development and person-focussed care provision. Experiences
      described in this paper require further examination and highlight substantial
      changes to nurse-patient relationships, health care and the way we practise.

PMID- 16907790
TI  - Participants' experiences of being interviewed about an emotive topic.
AB  - AIM: The aim of this paper was to report the experience of in-depth interviewing
      about emotive topics from the perspectives of participants. BACKGROUND: We both
      undertook qualitative, longitudinal studies investigating emotive topics using
      repeated in-depth interviews as the data collection method. Recruitment and some
      of the interviews took place at a potentially distressing time for participants,
      which raised concerns for us about issues relating to consent and the impact of
      the interviews on participants' emotional well-being. METHOD: At the end of the
      two studies, 55 participants were asked about their experiences of the
      recruitment and interview processes. The tape-recorded responses were transcribed
      verbatim. We both independently analysed the data before agreeing on the final
      thematic framework arising from participants' accounts. The data were collected
      in 1998 and 1999 (Study 1) and 2003 and 2005 (Study 2). FINDINGS: Some
      participants had initial reservations about participating in the studies. The
      primary reason for consenting was altruism, i.e. a belief that their
      participation might somehow help other families. Many participants often found it
      difficult to discuss emotive issues, particularly soon after the actual event,
      but all found it helpful to be given the opportunity to talk about their
      experiences to someone interested in what they had to say. None of the
      participants had concerns about, or regretted, being interviewed. CONCLUSION:
      Participants can find in-depth interviewing about emotive topics a helpful, even
      'therapeutic', experience. However, the purpose of the research interview is not
      to intentionally offer any form of therapy and researchers need to recognize and
      carefully consider this potential outcome at an early stage of the research
      process. Researchers studying emotive topics should also be aware of the possible
      impact of participants' experiences on their own emotional well-being.

PMID- 16907792
TI  - Psychometric properties of the Arabic version of Quality of Life Index.
AB  - AIM: This paper reports a study to translate the English language version of the
      Quality of Life Index into Arabic and estimate its reliability and content
      validity. BACKGROUND: Quality of life has become an important concern in health
      care and social policy. It is a difficult construct to define and measure, as it
      is determined by cultural, ethical, personal and religious values. The generic
      Ferrans and Powers Quality of Life Index was developed to measure quality of life
      of healthy individuals. Specific versions of the index were developed for
      particular diseases, such as diabetes, cancer and end-stage kidney disease. The
      instruments were initially developed for English-speaking clients and were later
      translated into several languages and used within a variety of cultures. However,
      there were no Arabic versions of the tool available to measure the quality of
      life of general populations or of people with particular diseases. METHOD: The
      Quality of Life Index was translated into Arabic using two of the techniques
      suggested in the literature for translation - back translation and bilingual
      technique. The same process was followed in the translation of the original scale
      and various disease-specific versions of the instrument. The work took place
      between 1995 and 2004. FINDINGS: The translated Arabic Quality of Life Index
      demonstrated a high degree of accuracy of translation and estimates of content
      validity. Subsequent to the translation of the original scale into Arabic, 13
      disease-related versions of the instrument were translated and are ready for use
      with clients who speak Arabic. Four of the versions have been used to collect
      data from clients. The results revealed high estimates of reliability for the
      generic, diabetes, cancer and dialysis versions. CONCLUSION: The Arabic version
      of the Quality of Life Index is highly reliable and has sufficient content
      validity for measuring quality of life of Arabic-speaking clients.

PMID- 16907791
TI  - Psychometric evaluation of the Chinese version of the Fagerstrom Tolerance
      Questionnaire as a measure of cigarette dependence.
AB  - AIM: The aim of this study is to estimate the psychometric properties of the
      Chinese version of the Fagerstrom Tolerance Questionnaire as a measure of
      nicotine dependence. BACKGROUND: The Chinese Fagerstrom Tolerance Questionnaire
      has been used in smoking cessation programmes in Taiwan. However, the
      psychometric properties of the Chinese version have not been tested. METHODS: A
      cross-sectional, descriptive study was conducted from June 2004 to July 2005 with
      247 adult smokers. The criterion validity of the Chinese Fagerstrom Tolerance
      Questionnaire was determined using two biomarkers (exhaled CO and saliva cotinine
      levels). Because the responses to the items are dichotomous or nominal, the
      validity and factorial structures were examined using tetrachoric techniques.
      Construct reliability was evaluated to accommodate the lack of tau-equivalence
      assumed in computing Cronbach's alpha. FINDINGS: The item 'smoke more in the
      morning' was not statistically significantly correlated with either biomarker
      because many participants expressed the desire to smoke after meals instead of in
      the morning. The items 'nicotine yield' and 'inhalation' performed poorly in
      terms of criterion validity and construct validity. This evidence supports
      modification of the Chinese version of the Fagerstrom Tolerance Questionnaire to
      the six-item Fagerstrom Test for Nicotine Dependence. In addition, the item
      'difficulty refraining from smoking in forbidden places' had relatively poor
      psychometric performance. The reason may be culturally specific, having to do
      with the relative lack of forbidden places and restrictions on tobacco use in
      Taiwan. The predictive ability of the Chinese version of the Fagerstrom Tolerance
      Questionnaire for biomarkers is higher than the English version. The reliability
      coefficient (0.65) was higher than Cronbach's alpha, but did not meet the
      satisfactory standard of 0.70. CONCLUSION: The Chinese version of the Fagerstrom
      Tolerance Questionnaire is a fairly reliable and valid scale, but needs to be
      revised to accommodate cross-cultural differences.

PMID- 16907793
TI  - Commentary on Halabi J.O. (2006) Psychometric properties of the Arabic version of
      Quality of Life Index. Journal of Advanced Nursing 55(5), 604-611.

PMID- 16907794
TI  - Improving understanding and rigour through triangulation: an exemplar based on
      patient participation in interaction.
AB  - AIM: In this paper, we aim to explore the benefits of triangulation and to expose
      the positive contribution of using 'triangulation for completeness' within a
      study of a complex concept, namely patient participation during healthcare
      interaction. BACKGROUND: Complex concepts, such as patient participation, are
      often the focus of nursing research. Triangulation has been proposed as a
      technique for studying complexity but, although debates about triangulation are
      becoming more prevalent in the literature, there is little deliberation about the
      process through which triangulation for completeness, with its claims of forming
      more comprehensive and rigorous descriptions of concepts through use of multiple
      data sources, yields it purported benefits. METHODS: A seminar series, held
      between 2001 and 2003, brought together researchers actively involved in the
      study of patient participation in healthcare consultations. The group came from
      diverse methodological traditions and had undertaken research with a range of
      informants and a range of methods. DISCUSSION: The various studies used
      triangulation at different levels: within studies, across studies and across
      disciplines. Our examples support theoretical arguments that triangulation for
      completeness can lead to a more holistic understanding of a concept and can
      improve scientific rigour. Furthermore, we suggest that triangulation can improve
      research skills for individuals. Our examples suggest that the process through
      which understanding is enhanced is discursive and centres on discussions of
      convergent and unique findings; rigour is improved is through challenging
      findings, being encouraged to explain aspects of your research that may be taken
      for granted and improving transparency; and individual researcher's skills and
      abilities are improved is through a process of discussion and reflexivity.
      CONCLUSIONS: Triangulation for completeness, on various levels, can improve the
      quality and utility of research about complex concepts through a range of
      discursive processes. Developing greater opportunity to collaborate at various
      levels of analysis could be an important development in nursing research.

PMID- 16907795
TI  - Assessing the relationships between contextual factors and research utilization
      in nursing: systematic literature review.
AB  - AIM: This paper reports a systematic literature review examining relationships
      between contextual factors and research utilization in nursing, examining the
      strength of these relationships, and mapping the contextual factors to the
      Promoting Action on Research Implementation in Health Services model of research
      implementation. BACKGROUND: Healthcare organizations have long struggled with how
      to improve clinical care outcomes. Understanding which contextual factors enhance
      nursing research utilization may support organizations in creating environments
      that facilitate the uptake of evidence in nursing practice to improve these
      outcomes. METHODS: A search of five electronic bibliographic databases and a
      manual search of specific journals were conducted for studies that were published
      in English and examined contextual factors as independent variables and research
      utilization as the dependent variable from the perspective of nurses working in
      clinical practice. The studies were assessed for quality of design, sample,
      measurement and statistical analysis. RESULTS: Ten papers met the search
      criteria. Six contextual factors were identified as having a statistically
      significant relationship with research utilization, namely the role of the nurse,
      multi-faceted access to resources, organizational climate, multi-faceted support,
      time for research activities and provision of education. The contextual factors
      could successfully be mapped to the dimensions of context in the Promoting Action
      on Research Implementation in Health Services framework (context, culture,
      leadership), with the exception of evaluation. CONCLUSION: The strength of the
      relationship between the six contextual factors and research utilization by
      nurses is still largely unknown as (a) few studies were found of sufficient
      quality because of methodological limitations and (b) the results in reviewed
      studies were mixed. More robust methods in future work would yield a better
      understanding of the full impact of contextual factors on nurses' use of
      research.

PMID- 16907796
TI  - Parenting children with diabetes and Belsky's Determinants of Parenting Model:
      literature review.
AB  - AIM: This paper provides a critical appraisal of the parenting literature as
      related to children with diabetes and proposes an adapted model of Belsky's
      Determinants of Parenting. BACKGROUND: Diabetes is the leading endocrine disease
      in school-aged children. As primary healthcare providers, parents assume
      responsibility for the daily management of their children's diabetes. It is
      therefore inevitable that parenting becomes a crucial variable in determining
      diabetes control. However, the literature examining parenting children with a
      chronic illness such as diabetes is limited. METHOD: A literature search was
      conducted using the CINAHL, EMBASE, PsychINFO, and Social Science Index databases
      and the terms 'parenting', 'determinants of parenting', 'Belsky's Determinants of
      Parenting' and combined with 'children' and 'type 1 diabetes'. Parenting and
      nursing literature from 1984 to 2004 was included if it was related to parenting
      determinants and diabetes control in children. The literature retrieved was
      critically appraised and synthesized in relation to Belsky's Determinants of
      Parenting Model. FINDINGS: By incorporating new knowledge, an adapted
      Determinants of Parenting Model is proposed. The adapted model reflects a bi
      directional relationship between parenting and child characteristics.
      Specifically, suggestions for future research on the adapted model and the bi
      directional relationship between parenting and child characteristics are also
      discussed. CONCLUSION: Recommendations are presented for use of the adapted
      Determinants of Parenting Model for future nursing research. Future research will
      need to focus on establishing causal links between the determinants, identifying
      the extent to which each determinant influences parenting, and parenting
      determinants questionnaire development.

PMID- 16907797
TI  - In response to: de Witt L. & Ploeg J. (2006) Critical appraisal of rigor in
      interpretive phenomenological nursing research. Journal of Advanced Nursing
      55(2), 215-229.

PMID- 16907801
TI  - History of science--spores.
AB  - Bacterial endospores were first studied 130 years ago by Cohn in 1876 and
      independently by Koch in the same year. Although spore dormancy and resistance
      have been much studied since then, questions still remain concerning the basic
      mechanisms and the kinetics of heat inactivation in particular. Likewise, the
      extreme dormancy and longevity of spores was recognized early on and later
      greatly extended but still evade complete understanding. Evidence has accumulated
      for the involvement of specific spore components such as calcium, dipicolinic
      acid, small acid soluble proteins in the core and peptidoglycan in the cortex.
      Involvement of physical factors too, such as the relative dehydration of the
      core, maybe in a high-viscosity state or even in a glassy state, has added to
      appreciation of the multicomponent nature of dormancy and resistance. Spore
      former morphology formed the basis for early classification systems of
      sporeformers from about 1880 and consolidated in the mid-1900s, well prior to the
      use of modern genetic procedures. With respect to sporulation, groundbreaking
      sequence studies in the 1950s provided the basis for later elucidation of the
      genetic control widely relevant to many cell differentiation mechanisms. With
      respect to the breaking of dormancy (activation and germination), the elucidation
      of mechanisms began in the 1940s following the observations of Hills at Porton
      who identified specific amino acid and riboside 'germinants', and laid the basis
      for the later genetic analyses, the identification of germinant receptor genes
      and the elucidation of key germination reactions. The nonexponential nature of
      germination kinetics has thwarted the development of practical Tyndallization
      like processing. So inactivation by heat remains the premier method of spore
      control, the basis of a huge worldwide industry, and still relying on the basic
      kinetics of inactivation of Clostridium botulinum spores, and the reasoning
      regarding safety first evolved by Bigelow et al. in 1920 and Esty and Meyer in
      1922. 'Newer' processes such as treatment with ionizing radiation (first proposed
      in 1905) and high hydrostatic pressure (first proposed in 1899) may be introduced
      if consumer resistance and some remaining technical barriers could be overcome.

PMID- 16907802
TI  - Spores of Bacillus subtilis: their resistance to and killing by radiation, heat
      and chemicals.
AB  - A number of mechanisms are responsible for the resistance of spores of Bacillus
      species to heat, radiation and chemicals and for spore killing by these agents.
      Spore resistance to wet heat is determined largely by the water content of spore
      core, which is much lower than that in the growing cell protoplast. A lower core
      water content generally gives more wet heat-resistant spores. The level and type
      of spore core mineral ions and the intrinsic stability of total spore proteins
      also play a role in spore wet heat resistance, and the saturation of spore DNA
      with alpha/beta-type small, acid-soluble spore proteins (SASP) protects DNA
      against wet heat damage. However, how wet heat kills spores is not clear,
      although it is not through DNA damage. The alpha/beta-type SASP are also
      important in spore resistance to dry heat, as is DNA repair in spore outgrowth,
      as Bacillus subtilis spores are killed by dry heat via DNA damage. Both UV and
      gamma-radiation also kill spores via DNA damage. The mechanism of spore
      resistance to gamma-radiation is not well understood, although the alpha/beta
      type SASP are not involved. In contrast, spore UV resistance is due largely to an
      alteration in spore DNA photochemistry caused by the binding of alpha/beta-type
      SASP to the DNA, and to a lesser extent to the photosensitizing action of the
      spore core's large pool of dipicolinic acid. UV irradiation of spores at 254 nm
      does not generate the cyclobutane dimers (CPDs) and (6-4)-photoproducts (64PPs)
      formed between adjacent pyrimidines in growing cells, but rather a thymidyl
      thymidine adduct termed spore photoproduct (SP). While SP is formed in spores
      with approximately the same quantum efficiency as that for generation of CPDs and
      64PPs in growing cells, SP is repaired rapidly and efficiently in spore outgrowth
      by a number of repair systems, at least one of which is specific for SP. Some
      chemicals (e.g. nitrous acid, formaldehyde) again kill spores by DNA damage,
      while others, in particular oxidizing agents, appear to damage the spore's inner
      membrane so that this membrane ruptures upon spore germination and outgrowth.
      There are also other agents such as glutaraldehyde for which the mechanism of
      spore killing is unclear. Factors important in spore chemical resistance vary
      with the chemical, but include: (i) the spore coat proteins that likely react
      with and detoxify chemical agents; (ii) the relative impermeability of the
      spore's inner membrane that restricts access of exogenous chemicals to the spore
      core; (iii) the protection of spore DNA by its saturation with alpha/beta-type
      SASP; and (iv) DNA repair for agents that kill spores via DNA damage. Given the
      importance of the killing of spores of Bacillus species in the food and medical
      products industry, a deeper understanding of the mechanisms of spore resistance
      and killing may lead to improved methods for spore destruction.

PMID- 16907803
TI  - How do spores germinate?
AB  - Spore germination, as defined as those events that result in the loss of the
      spore-specific properties, is an essentially biophysical process. It occurs
      without any need for new macromolecular synthesis, so the apparatus required is
      already present in the mature dormant spore. Germination in response to specific
      chemical nutrients requires specific receptor proteins, located at the inner
      membrane of the spore. After penetrating the outer layers of spore coat and
      cortex, germinant interacts with its receptor: one early consequence of this
      binding is the movement of monovalent cations from the spore core, followed by
      Ca2(+) and dipicolinic acid (DPA). In some species, an ion transport protein is
      also required for these early stages. Early events - including loss of heat
      resistance, ion movements and partial rehydration of the spore core - can occur
      without cortex hydrolysis, although the latter is required for complete core
      rehydration and colony formation from a spore. In Bacillus subtilis two crucial
      cortex lytic enzymes have been identified: one is CwlJ, which is DPA-responsive
      and is located at the cortex-coat junction. The second, SleB, is present both in
      outer layers and at the inner spore membrane, and is more resistant to wet heat
      than is CwlJ. Cortex hydrolysis leads to the complete rehydration of the spore
      core, and then enzyme activity within the spore protoplast resumes. We do not yet
      know what activates SleB activity in the spore, and neither do we have any
      information at all on how the spore coat is degraded.

PMID- 16907804
TI  - Single cell analysis of gene expression patterns of competence development and
      initiation of sporulation in Bacillus subtilis grown on chemically defined media.
AB  - AIM: Understanding the basis for the heterogeneous (or bistable) expression
      patterns of competence development and sporulation in Bacillus subtilis. METHODS
      AND RESULTS: Using flow cytometric analyses of various promoter-GFP fusions, we
      have determined the single-cell gene expression patterns of competence
      development and initiation of sporulation in a chemically defined medium (CDM)
      and in biofilms. CONCLUSIONS: We show that competence development and initiation
      of sporulation in a CDM are still initiated in a bistable manner, as is the case
      in complex media, but are sequential in their timing. Furthermore, we provide
      experimental proof that competence and sporulation can develop under conditions
      that normally do not trigger these processes. SIGNIFICANCE AND IMPACT OF THE
      STUDY: Some pathogens are able to develop natural competence, which is a serious
      medical problem with the increased acquired multi-drug resistance of these
      organisms. Another adaptive microbial response is spore formation. Because of
      their heat resistance and hydrophobicity, spores of a variety of species are of
      major concern for the food industry. Using the model organism B. subtilis, we
      show that competence development and sporulation are initiated in a bistable and
      sequential manner. We furthermore show that both processes may be noise-based,
      which has major implications for the control of unwanted differentiation
      processes in pathogenic and food-spoilage micro-organisms.

PMID- 16907805
TI  - Bacillus sporothermodurans and other highly heat-resistant spore formers in milk.
AB  - A recent example of a micro-organism causing undesired growth in consumer milk is
      Bacillus sporothermodurans producing highly heat-resistant spores (HRS) which may
      survive ultra-high temperature (UHT) treatment or industrial sterilization.
      Molecular typing showed a heterogeneous group of farm isolates (non-HRS strains),
      but a clonal group of UHT isolates from diverse European countries and other
      continents (HRS-clone) suggesting a common source. During a survey of Belgian
      dairy farms for the presence of potentially highly heat-resistant spore formers,
      high numbers of these spores were detected in filter cloth, green crop and fodder
      samples. The strain collection showed a high taxonomic diversity with 18
      potentially new species and with Bacillus licheniformis and Geobacillus pallidus
      as predominating species overall. Seventeen B. sporothermodurans isolates were
      identified, mainly originating from feed concentrate. Heat resistance studies
      showed the UHT resistance of B. sporothermodurans spores present in industrially
      contaminated UHT milk, but a lower heat resistance of laboratory-grown strains
      (HRS and non-HRS). Hydrogen peroxide, used as sanitizer in the dairy industry,
      was found to induce higher heat resistance of laboratory-grown B.
      sporothermodurans strains to a certain level. This indicates that sublethal
      stress conditions may affect the heat resistance. By transmission electron
      microscopy, structural differences at the spore level were found between HRS and
      non-HRS strains. The data indicate that the attainment of extreme heat resistance
      is rather multifactorial.

PMID- 16907806
TI  - Clostridium botulinum and the safety of minimally heated, chilled foods: an
      emerging issue?
AB  - Foodborne botulism is caused by consumption of preformed botulinum neurotoxin,
      with as little as 30 ng of neurotoxin being potentially lethal. Consumption of
      minute quantities of neurotoxin-containing food can result in botulism. In view
      of the severity of foodborne botulism, it is essential that new foods be
      developed safely without an increase in incidence of this disease. Minimally
      heated, chilled foods are a relatively new type of food, sales of which are
      currently increasing by about 10% per annum. These products meet consumer demand
      for high-quality foods that require little preparation time. Their safety and
      quality depends on mild heat treatment, chilled storage, restricted shelf life
      and sometimes on intrinsic properties of the foods. The principal microbiological
      hazard is nonproteolytic Clostridium botulinum, and there is a concern that this
      may become an emerging issue. A considerable amount of research and development
      over the last 15 years has underpinned the safe production of commercial,
      minimally heated, chilled foods with respect to foodborne botulism, and it is
      essential that safe food continues to be developed. In particular, the desire to
      use lighter heat processes and a longer shelf life presents a challenge that will
      only be met by significant developments in quantitative microbiological food
      safety.

PMID- 16907807
TI  - The use of clostridial spores for cancer treatment.
AB  - Hypoxic/necrotic regions, absent in normal tissues, can be exploited to target
      tumours in cancer therapy using nonpathogenic strains of the bacterial genus
      Clostridium. Following administration of Clostridium spores to tumour-bearing
      organisms, these spores can only germinate within the hypoxic/necrotic regions of
      solid tumours, proving their exquisite selectivity. Low oxygen tension is a
      common feature of solid tumours, which may arise from the unique physiological
      environment, generated to a large extent by the abnormal tumour vasculature, and
      provides as such a niche for anaerobic bacteria. Some clostridia tested clearly
      showed innate oncolytic activity, but they could not completely eradicate the
      tumour. Recombinant clostridia producing prodrug-converting enzymes or cytokines
      resulted in the production of such proteins solely within the tumour, and where
      applicable, could convert the prodrug in a toxic compound. Moreover, in some
      cases, tumour eradication or tumour control could be observed. This review brings
      an overview of the relative successes and failures of the Clostridium-directed
      tumour therapy with both wild-type strains and strains producing proteins useful
      in antitumour therapy.

PMID- 16907808
TI  - The Bacillus cereus group: novel aspects of population structure and genome
      dynamics.
AB  - AIMS: To provide new insights into the population and genomic structure of the
      Bacillus cereus group of bacteria. METHODS AND RESULTS: The genetic relatedness
      among B. cereus group strains was assessed by multilocus sequence typing (MLST)
      using an optimized scheme based on seven chromosomal housekeeping genes. A set of
      48 strains from different clinical sources was included, and six clonal complexes
      containing several genetically similar isolates from unrelated patients were
      identified. Interestingly, several clonal groups contained strains that were
      isolated from similar human sources. Furthermore, comparative whole genome
      sequence analysis of 16 strains led to the discovery of novel ubiquitous genome
      features of the B. cereus group, such as atypical group II introns, IStrons, and
      hitherto uncharacterized repeated elements. CONCLUSIONS: The B. cereus group
      constitutes a coherent population unified by the presence of ubiquitous and
      specific genetic elements which do not show any pattern, either in their
      sequences or genomic locations, which allows to differentiate between the member
      species of the group. Nevertheless, the population is very dynamic, as particular
      lineages of clinical origin can evolve to form clonal complexes. At the genome
      level, the dynamic behaviour is indicated by the presence of numerous mobile and
      repeated elements. SIGNIFICANCE AND IMPACT OF THE STUDY: The B. cereus group of
      bacteria comprises species that are of medical and economic importance. The MLST
      data, along with the primers and protocols used, will be available in a public,
      web-accessible database (http://mlstoslo.uio.no).

PMID- 16907809
TI  - Past, imminent and future human medical countermeasures for anthrax.
AB  - AIM: Anthrax is caused by the bacterium Bacillus anthracis. Although primarily a
      disease of animals, it can also infect man, sometimes with fatal consequences. As
      a result of concerns over the illicit use of this organism, considerable effort
      is focussed on the development of therapies capable of conferring protection
      against anthrax. This brief review will describe the efforts being made to
      address these issues. METHODS AND RESULTS: A review of the literature and the
      proceedings of the sixth international conference on anthrax, held in Santa Fe,
      USA in 2005 shows intense activity, but there has been as yet no real progress.
      While effective antibiotics, antitoxins and vaccines are available, concerns over
      their toxicity and the emergence of resistant strains have driven the development
      of second-generation products. The principal target for vaccine development is
      Protective Antigen (PA), the nontoxic cell-binding component of anthrax lethal
      toxin. While the recombinant products currently undergoing human clinical trials
      will offer considerable advantages in terms of reduced side effects and ease of
      production, they would still require multiple, needle-based dosing, and the
      inclusion of the adjuvant alum makes them expensive to administer and stockpile.
      To address these issues, researchers are developing vaccine formulations, which
      stimulate rapid protection following needle-free injection (nasal, oral or
      transcutaneous), and are stable at room temperature to facilitate stockpiling and
      mass vaccination programs. CONCLUSIONS: An array of medical countermeasures
      targeting B. anthracis will become available over the next 5-10 years.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The huge investment of research dollars is
      expected to dramatically expand the knowledge base. A better understanding of
      basic issues, such as survival in nature and pathogenesis in humans, will
      facilitate the development of new modalities to eliminate the threat posed by
      this organism.

PMID- 16907811
TI  - Beyond the spore--past and future developments of Bacillus thuringiensis as a
      biopesticide.
AB  - Formulated and sporulated cultures of Bacillus thuringiensis (Bt) are widely used
      as foliar sprays as part of integrated pest management strategies against insect
      pests of agricultural crops. Although in several cases the presence of the spore
      has been shown to improve the activity of the product, other Bt-based
      insecticides have been developed in which the spore is absent. The most notable
      of these are transgenic plants expressing just the insect toxin gene from the
      bacterium. This paper will discuss these developments, and the advantages and
      disadvantages of having the spore present.

PMID- 16907810
TI  - Do bacteria need to be regulated?
AB  - Additives for use in animal nutrition are regulated under Regulation (EC) No.
      1831/2003. The scope of this paper addresses the specific microbiological issues
      relevant to a microbial feed additive, containing a Bacillus spp. and uses as an
      example a product with the trade name, Calsporin. Bacillus subtilis C-3102 is the
      active ingredient in Calsporin and is added to animal feed to favourably affect
      animal production and performance (growth and feed efficiency), by modulating the
      gastrointestinal flora. It is not the purpose of this review to present the raw
      data for Calsporin but rather to use Calsporin as an example of the type of data
      required by the European regulatory authorities. At the time of preparation of
      this manuscript Calsporin has yet to be reviewed by the authorities. The
      regulatory system under the auspices of the EFSA FEEDAP Panel is clearly
      attempting to move in line with development of scientific opinion and is to be
      applauded for such efforts. Bacteria do need to be regulated, and the regulations
      clearly provide adequate and appropriate protection to human health and to
      environmental considerations.

PMID- 16907812
TI  - Bacillus species in the intestine of termites and other soil invertebrates.
AB  - Soil invertebrates harbour a complex microbial community in their intestinal
      system. The total number of microbes in the hindgut of soil invertebrates can
      reach a titre of 10(11) ml(-1). The gut microbes play an indispensable role in
      the digestion of food and are of ecological importance in the global carbon
      cycle. The gut microbiota can include a variety of micro-organisms from the three
      domains Bacteria, Archaea and Eucarya. The bacterial groups from the intestinal
      systems are mainly affiliated to the proteobacteria, the gram-positive groups
      Firmicutes and Actinobacteria, the Bacteroides/Flavobacterium branch and the
      spirochetes. The Archaea are represented by methanogens. The eukaryotic groups
      consist of protozoa, yeasts and fungi. Intestinal bacteria are involved in the
      degradation of cellulose, hemicellulose and aromatic compounds as well as
      nitrogen fixation. They also contribute to the redox status of the gut. Bacilli
      form a significant portion of the intestinal microbial community of soil
      invertebrates, especially among cellulose degraders. The diversity and function
      of bacilli in soil invertebrates will be discussed in this paper.

PMID- 16907813
TI  - In vitro effects of water activity, temperature and solutes on the growth rate of
      P. italicum Wehmer and P. digitatum Sacc.
AB  - AIMS: To evaluate the effect of water activity (a(w) 0.98-0.89, adjusted with
      glycerol, sorbitol, glucose, or NaCl) and temperature (5-25 degrees C) on the lag
      phase and radial growth rate (mm day(-1)) of the important citrus spoilage fungi,
      such as Penicillium italicum and Penicillium digitatum grown in potato dextrose
      agar (PDA) medium. To select, among models based on the use of different solutes,
      a model fitting accurately the growth of these species in relation to a(w) and
      temperature. METHODS AND RESULTS: Extensive data analyses showed for both
      Penicillium species a highly significant effect of a(w), temperature, solutes and
      their interactions on radial growth rate (P < 0.0001). Radial growth rate was
      inhibited and the lag phase (i.e. the time required for growth) lengthened as the
      a(w) of the medium decreased. NaCl appeared to causes the greatest stress on
      growth when compared with other nonionic solutes. Penicillium italicum stopped
      growing at 0.96 a(w) and P. digitatum at 0.93 a(w). Under the dry conditions
      where growth was observed, P. italicum grew faster than P. digitatum at low
      temperature and P. digitatum remained more active at ambient temperature.
      Multiple regression analysis applied to the square roots of the growth rates
      observed in the presence of each solute showed that both the 'glycerol model' and
      the 'sorbitol model' yielded a good prediction of P. italicum growth and the
      'sorbitol model' gave an accurate fit for P. digitatum growth, offering high
      quality prediction within the experimental limits described. CONCLUSIONS:
      Mathematical models describing and predicting, as a function of a(w) and
      temperature, the square root of the radial growth rate of the agents responsible
      for blue and green decays are important tools for understanding the behaviour of
      these fungi under natural conditions and for predicting citrus fruit spoilage.
      SIGNIFICANCE AND IMPACT OF THE STUDY: Implementation of these results should
      contribute towards a more rational control strategy against citrus spoilage
      fungi.

PMID- 16907814
TI  - Growth stimulation of Brevibacterium sp. by siderophores.
AB  - AIMS: To assess which types of siderophores are typically produced by
      Brevibacterium and how siderophore production and utilization traits are
      distributed within this genus. METHODS AND RESULTS: During co-cultivation
      experiments it was found that growth of B. linens Br5 was stimulated by B. linens
      NIZO B1410 by two orders of magnitude. The stimulation was caused by the
      production of hydroxamate siderophores by B. linens NIZO B1410 that enabled the
      siderophore-auxotrophic strain Br5 to grow faster under the applied iron-limited
      growth conditions. Different patterns of siderophore production and utilization
      were observed within the genus Brevibacterium. These patterns did not reflect the
      phylogenetic relations within the group as determined by partial 16S rDNA
      sequencing. Most Brevibacterium strains were found to utilize hydroxamate
      siderophores. CONCLUSIONS: Brevibacteria can produce and utilize siderophores
      although certain strains within this genus are siderophore-auxotrophic.
      SIGNIFICANCE AND IMPACT OF THE STUDY: It is reported for the first time that
      brevibacteria produce and utilize siderophores. This knowledge can be utilized to
      stimulate growth of auxotrophic strains under certain conditions. Enhancing the
      growth rate of Brevibacterium is of importance for the application of this
      species, for example, for cheese manufacturing or for industrial production of
      enzymes or metabolites.

PMID- 16907815
TI  - In vitro antibacterial activity of Lactobacillus helveticus strain KS300 against
      diarrhoeagenic, uropathogenic and vaginosis-associated bacteria.
AB  - AIMS: The purpose of this study was to investigate in vitro the antibacterial
      activity of the Lactobacillus helveticus strain KS300 against vaginosis
      associated bacteria including Gardnerella vaginalis and Prevotella bivia,
      uropathogenic Escherichia coli, and diarrhoeagenic Salmonella enterica serovar
      Typhimurium. METHODS AND RESULTS: The KS300 strain inhibited the growth of G.
      vaginalis, P. bivia, S. typhimurium, and pathogenic E. coli. After direct co
      culture, data show that the Lactobacillus strain decreased the viability of G.
      vaginalis, P. bivia, S. typhimurium, and pathogenic E. coli. The adhering KS300
      strain inhibited the adhesion of G. vaginalis DSM 4944 and uropathogenic Dr
      positive E. coli IH11128 onto HeLa cells. Moreover, the KS300 strain inhibited
      the internalization of uropathogenic Dr-positive E. coli IH11128 within HeLa
      cells and S. typhimurium SL1344 within Caco-2/TC7 cells. CONCLUSIONS: The
      findings demonstrate that L. helveticus strain KS300 is adhesive onto cultured
      human cells and has antagonistic activities against vaginosis-associated,
      uropathogenic and diarrhoeagenic pathogens. SIGNIFICANCE AND IMPACT OF THE STUDY:
      Adhering L. helveticus strain KS300 is a potential probiotic strain displaying a
      strain-specific array of in vitro antibacterial activities.

PMID- 16907816
TI  - Effect of pH, temperature and substrate on N2O, NO and CO2 production by
      Alcaligenes faecalis p.
AB  - AIMS: To study the effect of pH, temperature and substrate on the magnitude of
      N(2)O and NO production by heterotrophic nitrifiers. METHODS AND RESULTS: The
      change in N(2)O and NO production by the heterotrophic nitrifiers Alcaligenes
      faecalis subsp. parafaecalis and Paracoccus pantotrophus because of variations in
      pH, temperature and substrate was studied in chemostat cultures under steady
      state conditions. N(2)O, NO and CO(2) production increased with temperature
      between 4 and 32 degrees C. For N(2)O an optimum temperature of 28 degrees C was
      observed. No optimum temperature was found for NO. Highest N(2)O and CO(2)
      productions were observed at a pH of 7.0. However, besides having an optimum at
      pH 7.0, especially NO production but also N(2)O production increased
      significantly at pH <or= 4.0. This increase in NO production under acidic
      conditions was partly because of chemo-denitrification, which contributed up to
      62% of total NO production at pH 3.0 (0.8% for N(2)O). Furthermore, we could
      demonstrate that substrate quality significantly affects N(2)O, NO and CO(2)
      production. N(2)O and especially NO production by A. faecalis p. was
      significantly lower on an ammonium citrate medium when compared with rates
      obtained for a peptone-meat extract medium. CONCLUSIONS: The results indicate
      that heterotrophic nitrifiers are suitable model organisms to study the influence
      of environmental factors on microbial N trace gas production. SIGNIFICANCE IMPACT
      OF THE STUDY: The results allow an improved description, e.g. of the pH
      dependency of N trace gas production by microbes and/or chemo-denitrification in
      process-oriented models describing the exchange of N trace gases between soils
      and the atmosphere.

PMID- 16907817
TI  - Sources of the adventitious microflora of a smear-ripened cheese.
AB  - AIMS: To determine the relationships between the major organisms from the cheese
      making personnel and environment and the surface of a smear cheese. METHODS AND
      RESULTS: 360 yeast and 593 bacteria from the cheese surface, the dairy
      environment and the hands and arms of personnel were collected. Pulsed-field gel
      electrophoresis, repetitive sequence-based polymerase chain reaction and 16S rDNA
      sequencing were used for typing and identifying the bacteria, and mitochondrial
      DNA restriction fragment length polymorphism and Fourier-transform infrared
      spectroscopy for typing and identifying the yeast. The three most dominant
      bacteria were Corynebacterium casei, Corynebacterium variabile and Staphylococcus
      saprophyticus, which were divided into three, five and seven clusters,
      respectively, by macrorestriction analysis. The same clones from these organisms
      were isolated on the cheese surface, the dairy environment and the skin of the
      cheese personnel. Debaryomyces hansenii was the most dominant yeast. CONCLUSIONS:
      A 'house' microflora exists in the cheese plant. Although the original source of
      the micro-organisms was not identified, the brines were an important source of S.
      saprophyticus and D. hansenii and, additionally, the arms and hands of the
      workers the sources of C. casei and C. variabile. SIGNIFICANCE AND IMPACT OF THE
      STUDY: This is the first time that the major contribution of the house microflora
      to the ripening of a smear-ripened cheese has been demonstrated.

PMID- 16907818
TI  - Scaling-up in industrial winemaking using low electric current as an alternative
      to sulfur dioxide addition.
AB  - AIMS: To better understand the outcome of employing low electric current (LEC)
      technology as a new preservation and alternative in wine technology, and to
      contribute to its development. It is used in industrial-scale winemaking with
      commercial yeast (Saccharomyces cerevisiae) during the grape must fermentation.
      METHODS AND RESULTS: LEC (200 mA, time 16 days) was applied to fresh grape must
      as an alternative method to the usual sulfur dioxide addition used in the
      industrial process; two tanks, each 30,000 l, were employed for parallel
      fermentations. The results show that LEC decreased the survival time and
      increased the death rate of apiculate yeasts, whereas it did not affect the
      growth and survival of S. cerevisiae. A comparison was made of the main chemical
      and sensory parameters of the wines obtained. CONCLUSIONS: The results have
      demonstrated that the low-voltage treatment had a positive effect on the grape
      juice fermentation (yeast microflora) during the early stages of winemaking.
      SIGINIFICANCE AND IMPACT OF THE STUDY: These results could be of significant
      importance in developing, for 'biological wine', new winemaking technologies for
      an innovative control process of yeast fermentation.

PMID- 16907819
TI  - Optimization of a medium for enhancing nicotine biodegradation by Ochrobactrum
      intermedium DN2.
AB  - AIMS: To optimize a medium for nicotine degradation by Ochrobactrum intermedium
      DN2 in presence of yeast extract, glucose and Tween 80 using response surface
      methodology (RSM). METHODS AND RESULTS: In this study, the effects of yeast
      extract, glucose and Tween 80 on nicotine degradation were investigated in flasks
      using a novel nicotine-degrading bacterium, O. intermedium DN2. A full factorial
      central composite design was applied in the design of experiments and in the
      analysis of the experimental data. The results showed that the most significant
      variable influencing nicotine degradation was yeast extract, followed by glucose,
      and then Tween 80. Moreover these three factors interacted with each other and
      combined to produce positive effects on nicotine degradation. The experimental
      data also allowed the development of an empirical model (P < 0.0001) describing
      the inter-relationship between independent and dependent variables. By solving
      the regression equation, the optimal values of the variables were determined as:
      yeast extracts 0.094%, glucose 0.101% and Tween 80 0.080%. Using the medium
      obtained, about 1,220 mg l(-1) of nicotine was degraded (95.55%) within 10 h at
      the specific biodegradation of 116.59 mg l(-1) h(-1) in 30-l bioreactor
      containing 25-l tobacco extract. CONCLUSIONS: An optimal medium of nicotine
      degradation by the strain DN2 was obtained. SIGNIFICANCE AND IMPACT OF THE STUDY:
      RSM proved to be reliable in developing the model, optimizing factors and
      analysing interaction effects. The results provide better understanding on the
      interactions between yeast extract, glucose and Tween 80 for nicotine
      biodegradation.

PMID- 16907820
TI  - Bacterial community structure, compartmentalization and activity in a microbial
      fuel cell.
AB  - AIMS: To characterize bacterial populations and their activities within a
      microbial fuel cell (MFC), using cultivation-independent and cultivation
      approaches. METHODS AND RESULTS: Electron microscopic observations showed that
      the fuel cell electrode had a microbial biofilm attached to its surface with
      loosely associated microbial clumps. Bacterial 16S rRNA gene libraries were
      constructed and analysed from each of four compartments within the fuel cell: the
      planktonic community; the membrane biofilm; bacterial clumps (BC) and the anode
      biofilm. Results showed that the bacterial community structure varied
      significantly between these compartments. It was observed that
      Gammaproteobacteria phylotypes were present at higher numbers within libraries
      from the BC and electrode biofilm compared with other parts of the fuel cell.
      Community structure of the MFC determined by analyses of bacterial 16S rRNA gene
      libraries and anaerobic cultivation showed excellent agreement with community
      profiles from denaturing gradient gel electrophoresis (DGGE) analysis.
      CONCLUSIONS: Members of the family Enterobacteriaceae, such as Klebsiella sp. and
      Enterobacter sp. and other Gammaproteobacteria with Fe(III)-reducing and
      electrochemical activity had a significant potential for energy generation in
      this system. SIGNIFICANCE AND IMPACT OF THE STUDY: This study has shown that
      electrochemically active bacteria can be enriched using an electrochemical fuel
      cell.

PMID- 16907821
TI  - Evaluation of a new chromogenic agar for the detection of Listeria in food.
AB  - AIM: Rapid identification of Listeria in food is important in protecting
      consumers from infection. The development of chromogenic media such as agar
      Listeria according to Ottaviani and Agosti (ALOA) has allowed more rapid
      detection of Listeria monocytogenes, with presumptive identification of this
      pathogenic species after only 24 h of incubation. The aim of this study was to
      evaluate Oxoid chromogenic Listeria agar (OCLA) in comparison with ALOA and a
      traditional, nonchromogenic medium, Oxford agar. METHODS AND RESULTS: Media were
      compared using pure cultures, spiked food samples and naturally contaminated
      samples. Whilst development of typical colony morphology took 48 h on Oxford
      agar, Listeria spp. were frequently detected after 24 h of incubation on OCLA and
      ALOA. There was no significant difference in recovery between the two chromogenic
      media. CONCLUSIONS: Results indicate that OCLA gives equivalent recovery of
      Listeria spp. compared with ALOA. Whilst L. monocytogenes was frequently detected
      after 24 h of incubation, a 48-h incubation time was necessary to ensure
      detection of both L. monocytogenes and other Listeria spp. SIGNIFICANCE AND
      IMPACT OF THE STUDY: This study has shown that a commercially available
      chromogenic medium other than ALOA is appropriate for use in the international
      standard method. The commercial availability of more than one medium will
      facilitate the more widespread use of the method, thus increasing confidence in
      the ability to detect L. monocytogenes in food in the presence of other Listeria
      spp.

PMID- 16907822
TI  - Adhesion of water stressed Helicobacter pylori to abiotic surfaces.
AB  - AIM: The main aim of this work was to study and compare the adhesion of water
      exposed Helicobacter pylori to six different substrata and correlate any changes
      in morphology, physiology, ability to form aggregates and cultivability when in
      the planktonic or in the sessile phase. METHODS AND RESULTS: The number of total
      cells adhered for different water exposure times and modifications in the cell
      shape were evaluated using epifluorescence and scanning electron microscopy, and
      physiology assessed using Syto9 and propidium iodide (PI) cellular uptake. All
      abiotic surfaces were rapidly colonized by H. pylori, and colonization appeared
      to reach a steady state after 96 h with levels ranging from 2.3 x 10(6) to 3.6 x
      10(6) total cells cm(-2). Cell morphology was largely dependent on the support
      material, with spiral bacteria, associated with the infectious form of H. pylori,
      subsisting in a higher percentage on nonpolymeric substrata. Also, sessile
      bacteria were generally able to retain the spiral shape for longer when compared
      with planktonic bacteria, which became coccoid more quickly. The formation of
      large aggregates, which may act as a protection mechanism against the negative
      impact of the stressful external environmental conditions, was mostly observed on
      the surface of copper coupons. However, Syto9 and PI staining indicates that most
      of H. pylori attached to copper or SS304 have a compromised cell membrane after
      only 48 h. Cultivability methods were only able to detect the bacteria up to the
      2 h exposure-time and at very low levels (up to 500 CFU cm(-2)). CONCLUSIONS: The
      fact that the pathogen is able to adhere, retain the spiral morphology for longer
      and form large aggregates when attached to different plumbing materials appeared
      to point to pipe materials in general, and copper plumbing in particular, as a
      possible reservoir of virulent H. pylori in water distribution systems. However,
      the Syto9/PI staining results and cultivability methods indicate that the
      attached H. pylori cells quickly enter in a nonviable physiological state.
      SIGNIFICANCE AND IMPACT OF THE STUDY: This represents the first study of H.
      pylori behaviour in water-exposed abiotic surfaces. It suggests that co
      aggregation with the autochthonous heterotrophic consortia present in water is
      necessary for a longer survival of the pathogen in biofilms associated to
      drinking water systems.

PMID- 16907823
TI  - Sclerotial biomass and carotenoid yield of Penicillium sp. PT95 under oxidative
      growth conditions and in the presence of antioxidant ascorbic acid.
AB  - AIMS: To determine the effect of oxidative stress and exogenous ascorbic acid on
      sclerotial biomass and carotenoid yield of Penicillium sp. PT95. METHODS: In this
      experiment, high oxidative stress was applied by the inclusion of FeSO(4) in the
      growth medium and exposure to light. Low oxidative stress was applied by omitting
      iron from the growth medium and by incubation in the dark. Supplementation of
      exogenous ascorbic acid (as antioxidant) to the basal medium caused a
      concentration-dependent delay of sclerotial differentiation (up to 48 h),
      decrease of sclerotial biomass (up to 40%) and reduction of carotenoid yield (up
      to 91%). On the contrary, the exogenous ascorbic acid also caused a concentration
      dependent decrease of lipid peroxidation in colonies of this fungus. CONCLUSIONS:
      Under high oxidative stress growth condition, the sclerotial biomass and
      carotenoid yield of PT95 strain in each plate culture reached 305 mg and 32.94
      microg, which were 1.23 and 3.71 times higher, respectively, than those at low
      oxidative stress growth condition. These data prompted us to consider that in
      order to attain higher sclerotial biomass and pigment yield, the strain PT95
      should be grown under high oxidative stress and in the absence of antioxidants.
      SIGNIFICANCE AND IMPACT OF THE STUDY: These results suggest that strain PT95 may
      be used for solid-state fermentation of carotenoid production under high
      oxidative stress growth conditions.

PMID- 16907824
TI  - Impact of iron particles in groundwater on the UV inactivation of bacteriophages
      MS2 and T4.
AB  - AIMS: To investigate the impact of iron particles in groundwater on the
      inactivation of two model viruses, bacteriophages MS2 and T4, by 254-nm
      ultraviolet (UV) light. METHODS AND RESULTS: One-litre samples of groundwater
      with high iron content (from the Indianapolis Water Company, mean dissolved iron
      concentration 1.3 mg l(-1)) were stirred vigorously while exposed to air, which
      oxidized and precipitated the dissolved iron. In parallel samples,
      ethylenediaminetetra-acetic acid (EDTA) was added to chelate the iron and prevent
      formation of iron precipitate. The average turbidity in the samples without EDTA
      (called the 'raw' samples) after 210 min of stirring was 2.7 +/- 0.1 NTU while
      the average turbidity of the samples containing EDTA (called the 'preserved'
      samples) was 1.0 +/- 0.1 NTU. 'Raw' and 'preserved' samples containing
      bacteriophage MS2 were exposed to 254-nm UV light at doses of 20, 40, or 60 mJ
      (cm(2))(-1), while samples containing bacteriophage T4 were exposed to 2 or 5 mJ
      (cm(2))(-1), using a low pressure UV collimated beam. The UV inactivation of both
      phages in the 'raw' groundwater was lower than in the EDTA-'preserved'
      groundwater to a statistically significant degree (alpha = 0.05), due to the
      association of phage with the UV-absorbing iron precipitate particles. A phage
      elution technique confirmed that a large fraction of the phage that survived the
      UV exposures were particle-associated. CONCLUSIONS: Phages that are associated
      with iron oxide particles in groundwater are shielded from UV light to a
      measurable and statistically significant degree at a turbidity level of 2.7 NTU
      when the phage particle association is induced under experimental conditions.
      SIGNIFICANCE AND IMPACT OF THE STUDY: While the particle association of the phage
      in this study was induced experimentally, the findings provide further evidence
      that certain particles in natural waters and wastewaters (e.g. iron oxide
      particles) may have the potential to shield viruses from UV light.

PMID- 16907827
TI  - Robust salivary gland-specific transgene expression in Anopheles stephensi
      mosquito.
AB  - Malaria sporozoites invade the mosquito salivary glands and wait in the salivary
      duct until the next blood feeding. The mechanisms of the process and molecules
      involved in the salivary gland invasion remain largely unknown. To establish a
      robust salivary gland-specific transgene expression in Anopheles stephensi, we
      obtained a salivary gland-specific promoter for a gene encoding anopheline
      antiplatelet protein (AAPP). The aapp promoter is a female salivary gland
      specific and blood meal-inducible strong promoter. Using this promoter, we
      generated a transgenic An. stephensi expressing abundant Discosoma sp. red
      fluorescent protein (DsRed) in the distal-lateral lobes of the glands, where the
      sporozoites invade preferentially. These results open up the possibilities of
      elucidating salivary gland-parasite interactions and generating transgenic
      mosquitoes refractory to parasites.

PMID- 16907826
TI  - A novel association between clustered NF-kappaB and C/EBP binding sites is
      required for immune regulation of mosquito Defensin genes.
AB  - A comparative analysis identified key cis-acting regulatory elements responsible
      for the temporal control of mosquito Defensin gene expression. The promoters of
      Anopheles gambiae Defensin 1 and two isoforms of Aedes aegypti Defensin A are up
      regulated by immune challenge. This stimulated activity depends upon a cluster of
      three NF-kappaB binding sites and closely associated C/EBP-like motifs, which
      function as a unit for optimal promoter activity. Binding of NF-kappaB and C/EBP
      like transcription factors is confirmed by electrophoretic mobility shift assay,
      including supershifts with antibodies to C/EBP. KappaB-like motifs are abundant
      within antimicrobial peptide gene promoters and most are very closely associated
      with putative C/EBP binding sites. This novel association between NF-kappaB and
      C/EBP binding sites may, therefore, be of widespread significance.

PMID- 16907828
TI  - Analysis of fat body transcriptome from the adult tsetse fly, Glossina morsitans
      morsitans.
AB  - Tsetse flies (Diptera: Glossinidia) are vectors of pathogenic African
      trypanosomes. To develop a foundation for tsetse physiology, a normalized
      expressed sequence tag (EST) library was constructed from fat body tissue of
      immune-stimulated Glossina morsitans morsitans. Analysis of 20,257 high-quality
      ESTs yielded 6372 unique genes comprised of 3059 tentative consensus (TC)
      sequences and 3313 singletons (available at http://aksoylab.yale.edu). We
      analysed the putative fat body transcriptome based on homology to other gene
      products with known functions available in the public domain. In particular, we
      describe the immune-related products, reproductive function related yolk proteins
      and milk-gland protein, iron metabolism regulating ferritins and transferrin, and
      tsetse's major energy source proline biosynthesis. Expression analysis of the
      three yolk proteins indicates that all are detected in females, while only the
      yolk protein with similarity to lipases, is expressed in males. Milk gland
      protein, apparently important for larval nutrition, however, is primarily
      synthesized by accessory milk gland tissue.

PMID- 16907830
TI  - piggyBac-like elements in the tobacco budworm, Heliothis virescens (Fabricius).
AB  - We identified two different groups of piggyBac-like elements (PLE) in the tobacco
      budworm, Heliothis virescens, and named them HvPLE1 and HvPLE2. An intact copy of
      HvPLE1 revealed the characteristics of PLE: inverted terminal repeats, inverted
      subterminal repeats, and an open reading frame encoding transposase, whereas
      other HvPLE1 copies and all the HvPLE2 copies carried disruptive mutations in the
      region encoding transposase. We also identified none to two bands per genome
      hybridized to a probe of Trichoplusia ni piggyBac in genomic Southern blotting,
      which are different from HvPLE1 or HvPLE2. Analysis of the sequences of multiple
      copies of HvPLE1 and HvPLE2 suggests that the PLEs are closely related to the T.
      ni piggyBac, of relatively young age, and independently entered the H. virescens
      genome.

PMID- 16907829
TI  - Characterization of BGTG-1, a tergal gland-secreted alpha-amylase, from the
      German cockroach, Blattella germanica (L.).
AB  - The protein fraction of the German cockroach, Blattella germanica (L.), tergal
      gland secretion was examined. SDS-PAGE separation of proteins present in B.
      germanica tergal gland secretion revealed a tergal gland-secreted protein, BGTG
      1, at approximately 63 kDa. BGTG-1 first appeared in tergal gland secretion at 2
      days postimaginal moult and the amount of protein observed increased through day
      5. A 2051 bp cDNA sequence, bgtg-1, was obtained by RACE polymerase chain
      reaction and contains a 1494 bp ORF encoding a predicted protein of 498 amino
      acids. In a Northern hybridization experiment using total RNA from B. germanica
      tergal gland tissue, a (32)P-labelled bgtg-1 probe hybridized to an RNA
      approximately 2000 bp and confirmed the 2051 bp cDNA size obtained by RACE PCR.
      Using the BLASTx sequence similarity search tool, the top match to the bgtg-1 ORF
      was found to be an alpha-amylase from Drosophila kikkawai (e-value = 1 x 10(
      178)). Alignment of the bgtg-1 deduced protein sequence with alpha-amylases from
      fruit fly, Drosophila melanogaster, honey bee, Apis mellifera (L.) and yellow
      mealworm, Tenebrio molitor (L.), revealed conserved residues throughout the ORF
      and sequence identities ranging from 58.4 to 58.2%. Using a gel-based assay,
      degradation of starch by native BGTG-1 was demonstrated in vitro and we propose
      that BGTG-1 may be involved in processing phagostimulatory sugars present in B.
      germanica tergal gland secretion.

PMID- 16907831
TI  - Differential expression of two glutathione S-transferases identified from the
      American dog tick, Dermacentor variabilis.
AB  - Reciprocal signalling and gene expression play a cardinal role during pathogen
      host molecular interactions and are prerequisite to the maintenance of balanced
      homeostasis. Gene expression repertoire changes during rickettsial infection and
      glutathione-S-transferases (GSTs) were among the genes found up-regulated in
      Rickettsia-infected Dermacentor variabilis. GSTs are well known to play an
      important part in cellular stress responses in the host. We have cloned two full
      length GSTs from D. variabilis (DvGST1 and DvGST2). Comparison of these two DvGST
      molecules with those of other species indicate that DvGST1 is related to the
      mammalian class theta and insect class delta GSTs, while DvGST2 does not seem to
      fall in the same family. Northern blotting analyses revealed differential
      expression patterns, where DvGST1 and DvGST2 transcripts are found in the tick
      gut, with DvGST2 transcripts also present in the ovaries. Both DvGST transcripts
      are up-regulated upon tick feeding. Challenge of fed adult ticks with Escherichia
      coli injection showed decreased transcript amounts compared with ticks injected
      with phosphate-buffered saline (sham) and naive ticks.

PMID- 16907832
TI  - Genome-wide analysis of phenobarbital-inducible genes in Drosophila melanogaster.
AB  - An oligoarray analysis was conducted to determine the differential expression of
      genes due to phenobarbital exposure in Drosophila melanogaster (w(1118) strain)
      third instar larvae. Seventeen genes were observed to be induced with increased
      expression by a statistical analysis of microarrays approach with a q < or =
      0.05. At q < or = 0.12, four more genes (Cyp12d1, DmGstd4, and two genes with
      unknown function) were found to be up-regulated, and 11 genes with unknown
      function were found to be down-regulated. Fifteen of these genes, Cyp4d14,
      Cyp6a2, Cyp6a8, Cyp12d1, Cyp6d5, Cyp6w1, CG2065, DmGstd6, DmGstd7, Amy-p/Amy-d,
      Ugt86Dd, GC5724, Jheh1, Jheh2 and CG11893, were verified using quantitative real
      time polymerase chain reaction. Some of these genes have been shown to be over
      transcribed in metabolically DDT-resistant Drosophila strains.

PMID- 16907833
TI  - A female-specific desaturase gene responsible for diene hydrocarbon biosynthesis
      and courtship behaviour in Drosophila melanogaster.
AB  - Drosophila melanogaster shows sexually dimorphic cuticular hydrocarbons, with
      monoenes produced in males and dienes produced in females. Here we describe a
      female-specific desaturase gene, desatF. RNAi knock-down led to a dramatic
      decrease in female dienes and increase in monoenes paralleled with an increase in
      copulation latency and a decrease in courtship index and copulation attempts by
      the males. The desatF gene was also expressed in females from D. sechellia, rich
      in dienes, but not D. simulans, which produce only monoenes. When hydrocarbons
      were feminized in D. melanogaster males by targeted expression of the transformer
      gene, the expression of desatF occurred. These results strongly suggest that
      desatF is a crucial enzyme for female pheromone biosynthesis and courtship
      behaviour in D. melanogaster.

PMID- 16907835
TI  - Cloning and characterization of protease inhibitor-like cDNAs from the Hessian
      fly mayetiola destructor (SAY).
AB  - Analysis of transcriptomes from the salivary glands and midgut of Hessian fly
      larvae Mayetiola destructor (say) identified a set of diverse cDNAs that encode
      proteins with a relatively high percentage (over 10%) of cysteinyl residues.
      Structural comparison of these putative proteins with known sequences in GenBank
      revealed that the positions of the cysteinyl residues in the identified proteins
      were highly conserved within a family of proteinase inhibitors despite very
      little overall sequence similarity. Phylogenetic analysis sorted this set of
      cDNAs into five different groups. To determine if these cDNAs indeed encode
      proteinase inhibitors, recombinant proteins were generated with two cDNAs from
      two different groups. Biochemical analysis of the recombinant proteins against
      commercial and insect gut proteinases demonstrated that the recombinant proteins
      are strong proteinase inhibitors with different specificities. Northern blot and
      real-time PCR analysis revealed that the different genes were expressed at
      different developmental stages and in different tissues. The overall results
      indicated that M. destructor contains a complex of genes that code for proteinase
      inhibitors which may regulate proteinase activities in different regulatory
      pathways. The GenBank accession numbers for the cDNAs in this paper were DQ232690
      to DQ232718.

PMID- 16907836
TI  - A tapeworm molecule manipulates vitellogenin expression in the beetle Tenebrio
      molitor.
AB  - Metacestodes of Hymenolepis diminuta secrete a molecule that decreases
      vitellogenin (Vg) synthesis in the beetle host, Tenebrio molitor. The 5608 bp T.
      molitor Vg cDNA represents a single-copy gene encoding a single open reading
      frame of 1821 amino acids with a predicted molecular mass of 206 kDa. Northern
      blot analysis revealed detectable levels of transcripts only in adult females. In
      vivo, Vg mRNA abundance was significantly higher in fat bodies from infected
      females compared with control females at all but the earliest time point. In
      vitro, Vg mRNA abundance was significantly increased in fat bodies incubated with
      live stage I-II parasites. The apparent conflict between increased Vg mRNA
      abundance and decreased Vg protein in fat bodies from infected females is
      discussed.

PMID- 16907834
TI  - Transcriptional response of Choristoneura fumiferana to sublethal exposure of
      Cry1Ab protoxin from Bacillus thuringiensis.
AB  - Bacillus thuringiensis is a microbial control agent active against Choristoneura
      fumiferana, a lepidopteran defoliator of North American forests. Although the B.
      thuringiensis insecticidal crystal protoxins have a relatively narrow host range,
      there is concern about their impact on non-target species where intoxication
      effects may not be overt. Larval toxicity effects can be assessed at the
      molecular level by determining altered transcriptional profiles in response to
      sublethal protoxin exposure in sensitive insects. Subtraction hybridization
      libraries were created using two larval populations, control and protoxin-fed and
      were characterized by sequencing 1091 clones. Differential mRNA expression of
      selected clones, as measured by quantitative polymerase chain reaction,
      identified a number of metabolic and stress-related genes that were either
      transcriptionally enhanced or repressed after protoxin exposure.

PMID- 16907837
TI  - Germ-line transformation and RNAi of the ladybird beetle, Harmonia axyridis.
AB  - To elucidate the molecular mechanisms underlying the tremendous diversity of
      insect wing colour patterns, it is imperative to identify and functionally
      characterize the genes involved in this developmental process. Here we report the
      first successful germ-line transformation using the transposable element vector
      piggyBac in the ladybird beetle Harmonia axyridis, which demonstrates typical
      genetic polymorphism in its wing colour patterns. The transformation efficiency
      by piggyBac was 3.7% per fertile G(0). We investigated the effectiveness of RNAi
      in Harmonia by injecting EGFP (enhanced green fluorescent protein) dsRNA into
      early transgenic EGFP-expressing embryos and observed substantial reduction of
      EGFP fluorescence in 87.2% of hatched larvae. Application of these new genetic
      tools to non-model insects such as Harmonia will facilitate the broad
      understanding of developmental mechanisms and evolutionary processes that are
      inaccessible using established model systems.

PMID- 16907838
TI  - Molecular, biochemical and histochemical characterization of two
      acetylcholinesterase cDNAs from the German cockroach Blattella germanica.
AB  - Full length cDNAs encoding two acetylcholinesterases (AChEs; Bgace1 and Bgace2)
      were cloned and characterized from the German cockroach, Blattella germanica.
      Sequence analyses showed that both genes possess all the typical features of ace,
      and that Bgace1 is orthologous to the insect ace1 whereas Bgace2 is to the insect
      ace2. Transcript level of Bgace1 was significantly higher (c. 10 fold) than that
      of Bgace2 in all 11 tissues examined, suggesting that Bgace1 likely encodes a
      predominant AChE. Multiple AChE bands were identified by native polyacrylamide
      gel electrophoresis and isoelectricfocusing from various tissue preparations,
      among which ganglia produced distinct two major and two minor AChE bands,
      indicative of the presence of at least two active AChEs. B. germanica AChEs
      appeared to be mainly localized in the central nervous system as demonstrated by
      histochemical activity staining, together with quantitative analysis of Bgace
      transcripts. Fluorescence in situ hybridization of the 1st thoracic ganglion
      confirmed that Bgace1 is predominantly transcribed and further showed that its
      transcript is found in almost entire region of inter or motor neurones including
      the cell bodies and axonal/dendritic branches. Bgace2 transcript is found only in
      the subset of neurones, particularly in the cell body. In addition, certain
      neurones were observed to express Bgace1 only.

PMID- 16907839
TI  - Differential expression of the detoxification genes in the different life stages
      of the malaria vector Anopheles gambiae.
AB  - The diverse habitats and diets encountered during the life cycle of an Anopheles
      mosquito have necessitated the development of extensive families of
      detoxification enzymes. Expansion of the three detoxification enzyme families
      (cytochrome P450s, carboxylesterases and glutathione transfereases), has occurred
      in mosquitoes compared with Drosophila, however, very little is known regarding
      the developmental expression of theses genes. Using a custom made microarray we
      determined the expression profile of the detoxification genes in adults, larvae
      and pupae of the malaria vector A. gambiae. The expression of approximately one
      quarter of these genes was developmentally regulated. The expression profile of
      each of these genes and the information this data provides on putative functions
      of the mosquito detoxification enzymes is discussed.

PMID- 16907841
TI  - Potential role of recombinant factor FVIIa in prophylaxis in severe hemophilia
      patients with inhibitors.

PMID- 16907842
TI  - Hepatitis C - contamination of toothbrushes: myth or reality?
AB  - Chronic hepatitis C patients are advised not to share toothbrushes, razors, nail
      scissors or other personal articles that potentially may have been in contact
      with blood, with others. This study examines the contamination of toothbrushes in
      patients with chronic hepatitis C as a model for a possible unconventional way of
      transmission. In 30 patients with chronic hepatitis C, 2 mL of saliva (before and
      after toothbrushing) and the toothbrush rinsing water after toothbrushing were
      tested for HCV-RNA. Saliva before and after toothbrushing was positive for HCV
      RNA in nine (30%) and 11 patients (36.7%), respectively. Twelve of the toothbrush
      rinsing water specimens (40%) tested HCV-RNA-positive. In six of these 12
      patients, the 'native' saliva had been negative for HCV-RNA. Patients with HCV
      RNA-positive toothbrush rinsing water showed no significant differences from
      those with negative rinsing water with respect to certain clinical, biochemical
      and virological parameters. In conclusion, our study demonstrates a contamination
      with HCV-RNA of a considerable portion of toothbrushes used by hepatitis C
      patients, suggesting at least a theoretical risk of infection by sharing these
      objects and strengthening the recommendations to take care of a clear separation
      of these personal care objects between patients and their household members.

PMID- 16907843
TI  - Virological analysis, genotypes and mutational patterns of the HBV precore/core
      gene in HBV/HCV-related hepatocellular carcinoma.
AB  - We investigated the replicative profile of hepatitis B (HBV) and hepatitis C
      (HCV) viruses and the mutational pattern of the HBV precore/core (pre-C/C) domain
      in hepatocellular carcinoma (HCC). Thirty-eight consecutive patients with HCC
      were included in the study - 18 of them with HBV/HCV co-infection and 20 with HBV
      single infection. Twenty-three additional patients with co-infection, without HCC
      were recruited as the control group. Replication activity was evaluated by
      detecting and quantitating both HBV and HCV genomes. The HBV pre-C/C region,
      encompassing the pregenome encapsidation signal involved in viral replication,
      was analysed by direct sequencing. HBV viraemia levels were significantly lower
      (P = 0.04) in patients with co-infection in comparison with single-infected HCC,
      whereas two different HBV viraemia profiles were detected in co-infection with or
      without circulating HCV. HBV genotype D was prevalent in the three groups and HCV
      genotype 1b was found to be the infecting strain in all patients. Lower
      variability in the pre-C/C region was found in co-infection in comparison with
      HBV single infection (P = 0.0004). A synonymous T1936C mutation was found in all
      co-infected HCC cases not related to the presence or absence of circulating HCV,
      and a hypermutated pre-C strain, characterized by the same mutational pattern,
      was identified in three HCC cases. The mutational pattern of the pre-C/C region
      was closely related to HBV replication efficiency, and specific HBV mutations
      selectively associated with HCV co-infection could be linked with accelerated
      HBV/HCV-related disease progression.

PMID- 16907844
TI  - Site-specific mutation of the interferon sensitivity-determining region (ISDR)
      modulates hepatitis C virus replication.
AB  - The number of amino acid substitutions in the interferon sensitivity-determining
      region (ISDR) in the nonstructural 5A (NS5A) gene of hepatitis C virus (HCV) is
      closely associated with the interferon (IFN) response and viral load. Several HCV
      replicon-based studies have reported that ISDR sequences had an influence on
      viral replication in vitro. However, it is unclear as to how different ISDR
      sequences affect HCV replication. Various clinically observed ISDR sequences were
      introduced into HCV replicons and their contribution to viral replication was
      investigated using a colony formation assay and/or a transient replication assay.
      A mapping study of the ISDR was performed to identify the amino acid positions
      that critically affect replication. While no colonies were formed in the colony
      formation assay using HCV replicons with few mutations (0, 1 and 3) in the ISDR,
      numerous colonies (>200) appeared when using constructs with six mutations.
      Introduction of various distinct ISDR sequences with multiple mutations resulted
      in replication enhancement in transient assays. A mapping study identified
      several specific sites in the ISDR that critically affected replication,
      including codon 2209 which, in patients, was closely associated with a strong
      response to IFN. ISDR sequences associated with a clinical IFN response and viral
      load modulated the replication of HCV replicons, suggesting the importance of the
      ISDR sequence in HCV infection.

PMID- 16907845
TI  - Hepatitis B virus reactivation in patients receiving chemotherapy for
      malignancies: role of precore stop-codon and basic core promoter mutations.
AB  - Hepatitis B virus (HBV) strains carrying the precore stop-codon mutation (A1896)
      have been considered among the predisposing factors for reactivation during
      chemotherapy for malignancies. The role of the T1762/A1764 basic core promoter
      (BCP) mutations has not been fully evaluated. We aimed to record any changes in
      HBV serological markers after reactivation, detect the presence of A1896 and BCP
      mutations and evaluate the type of cytotoxic drugs involved. We retrospectively
      screened eight patients presenting with HBV reactivation following chemotherapy
      for malignancies. The chemotherapy regimens used included corticosteroids (CSs),
      fludarabine and cyclophosphamide/adriamycine. The INNO-LiPA HBV PreCore kit was
      used for the detection of the A1896 and BCP mutations. Six patients who were
      hepatitis B surface antigen (HBsAg)-(+)/hepatitis B e antigen (HBeAg)-(-) before
      chemotherapy, had disease reactivation following a mean of four cycles of
      chemotherapy. Four survived and two died of hepatic failure. At the time of
      reactivation, all six patients carried the A1896 and five of them the BCP
      mutations. The remaining two patients were HBsAg-(-)/anti-HBs-(+)/anti-hepatitis
      B core (HBc)-(+)/HBeAg-(-) before chemotherapy. One of them reverted to HBeAg-(+)
      status but remained HBsAg-(-), while the other became HBsAg-(+)/HBeAg-(+),
      following three and eight cycles of fludarabine treatment, respectively. The
      former carried the A1896 and the latter the wild-type virus. Both died from
      causes associated with their haematological disease. All but one of our patients
      with HBV reactivation during chemotherapy carried the precore stop-codon and BCP
      mutations. Whether this occurs more frequently in such patients than those
      carrying the wild-type virus needs further investigation. Fludarabine should be
      added to the list of drugs inducing HBV reactivation. HBV reactivation following
      fludarabine treatment occurred in HBsAg-(-) patients who had been anti-HBs-(+).

PMID- 16907846
TI  - Antepartum immunoprophylaxis of three doses of hepatitis B immunoglobulin is not
      effective: a single-centre randomized study.
AB  - To investigate the efficacy of antepartum administration of three doses of
      hepatitis B immunoglobulin (HBIg), currently being used in China, 250 pregnant
      women who were seropositive for hepatitis B e antigen (HBeAg) were randomly
      divided into study (117 cases) and control groups (133 cases). Subjects in the
      study group received HBIg 400 IU intramuscularly once a month at the third,
      second and first month before delivery; subjects in the control group received no
      antepartum treatment. All neonates received passive-active immunization after
      birth. The maternal hepatitis B virus (HBV) markers, hepatitis B surface antigen
      (HBsAg) titres and HBV deoxyribonucleic acid (DNA) levels were measured at week
      28 of gestation (before the antepartum treatment) and at labour; the neonatal
      serum HBV markers were detected at birth and at 12 months after birth. No side
      effects were found in any of the women or their neonates. No statistical
      differences were seen between the maternal HBsAg and HBV DNA levels of the study
      and control groups at labour nor the protective efficacy rates of postnatal
      immunoprophylaxis at 12 months after birth (P > 0.05, respectively). To conclude,
      antepartum administration of three doses of HBIg for the HBeAg-positive women is
      inefficacious.

PMID- 16907847
TI  - HBV genes induce cytotoxic T-lymphocyte response upon adeno-associated virus
      (AAV) vector delivery into dendritic cells.
AB  - Hepatitis B virus (HBV) has been an increasing problem throughout the world and
      remains difficult to treat. But immunotherapeutic approaches offer new, effective
      treatments. Three recombinant adeno-associated virus (AAV) type 2 vectors,
      carrying one of the HBV S, C or X gene, were used to load (transduce)
      professional antigen-presenting dendritic cells (DC) for the purpose of
      stimulating cytotoxic T lymphocytes (CTL) in vitro. It was found that all three
      recombinant AAV/HBV antigen virus loaded DC at approximately 90% transduction
      efficiency. Most importantly, all three AAV-loaded DC stimulated rapid, antigen
      specific and major histocompatibility complex (MHC)-restricted CTL. In vitro,
      these CTL killed (30-50%) synthetic antigen-positive autologous targets as well
      as HepG2 liver cell targets. In comparing the three antigens, it was found that
      AAV/HBV-C-derived CTL consistently had the highest killing efficiency. CTL
      derived from AAV/HBV-C-loaded DC also showed significantly higher killing of
      targets than that from bacterially generated C-protein-loaded DC. Further studies
      showed that AAV/HBV-C-derived CTL had higher interferon (IFN)-gamma. These data
      suggest that AAV/HBV antigen gene-loading of DC may be useful for
      immunotherapeutic protocols against HBV infection and that the HBV C antigen may
      be the most useful for this purpose.

PMID- 16907848
TI  - Decline in haemoglobin A1c values in diabetic patients receiving interferon-alpha
      and ribavirin for chronic hepatitis C.
AB  - Haemoglobin A1c (A1c) levels are lower during haemolysis because of the shorter
      exposure of haemoglobin (Hb) to plasma glucose. Ribavirin (RBV) used in
      combination with interferon-alpha (IFN) for chronic hepatitis C causes reversible
      haemolytic anaemia. This study examined the extent to which RBV treatment
      influences A1c levels in diabetic patients. A retrospective analysis identified
      32 diabetic patients who underwent hepatitis C treatment with IFN and RBV. Each
      subject had at least three measures of A1c, Hb and glucose: before, during and
      after therapy. A1c values decreased from a mean pretreatment level of 7.2% to an
      on-treatment A1c level of 5.2% [mean paired difference -2.01%; 95% confidence
      interval (CI) -1.59% to -2.43%; P < 0.001]. During therapy, mean Hb levels
      decreased from 15.1 g/dL at baseline to a nadir of 11.7 g/dL (P < 0.001) with a
      rise in lactose dehydrogenase levels and reticulocyte counts, and unchanged mean
      corpuscular volume values confirming haemolysis. At the same time, glucose levels
      declined by a mean of 38.4 mg/dL (95% CI 13.4-63.5 mg/dL; P = 0.002) as did body
      weights by a mean of 3.15 kg (P < 0.001). According to published glucose-A1c
      correlation tables, this decline of glucose concentration by 38.4 mg/dL
      correlates to a decline in A1c level of 1.08%. In conclusion, reductions of A1c
      levels by a mean of 2.01% during hepatitis C therapy with IFN + RBV are due to a
      combination of decreased glucose levels (1.08%) and RBV-induced haemolysis
      (0.93%). A1c levels should not be measured during hepatitis C treatment with IFN
      + RBV because they do not adequately reflect glycaemic control.

PMID- 16907849
TI  - Association of TNF-alpha promoter polymorphisms with the outcomes of hepatitis B
      virus infection in Chinese Han population.
AB  - Host genetic factors and environment factors including hepatitis B virus (HBV)
      genotypes are widely studied for the different outcomes of HBV infection. Recent
      studies suggest that tumour necrosis factor-alpha (TNF-alpha) plays a pivotal
      role in the viral clearance and host immune response to HBV, and the capacity for
      TNF-alpha production in individuals is influenced by a major genetic component.
      In this study, we aimed to explore whether the single-nucleotide polymorphisms
      (SNPs) of TNF-alpha promoter are associated with the outcomes of HBV infection in
      the Chinese Han population. One hundred and forty-three spontaneously recovered
      HBV subjects and 196 chronic hepatitis B patients were recruited in this case
      control study in the Beijing area of China. Polymerase chain reaction-restriction
      fragment-length polymorphism (PCR-RFLP) and sequence-specific primer-PCR (SSP
      PCR) were used to detect the SNPs of five sites in the TNF-alpha promoter (
      238G/A, -308G/A, -857C/T, -863C/A, -1031T/C). The frequency distributions of
      genotypes and haplotypes in two groups were analysed by EPI and EH programs. The
      presence of the -238GG genotype was significantly correlated with persistence of
      HBV infection (OR = 4.08, P = 0.02), and -857TT genotype appeared in relation to
      the spontaneous clearance of HBV (OR = 0.47, P = 0.03). Frequency of haplotype
      GGCCT (-238/-308/-857/-863/-1031) in the chronic HB group was significantly lower
      than that in spontaneously recovered group (P = 0.03), and frequencies of
      haplotypes GGCAT and GGTAT in the chronic HB group were significantly higher than
      those in the spontaneously recovered group (P = 0.0001, P = 0.0004). In
      conclusion, TNF-alpha promoter polymorphisms are independently associated with
      different outcomes of HBV infection.

PMID- 16907850
TI  - Increased intrahepatic and circulating levels of endoglin, a TGF-beta1 co
      receptor, in patients with chronic hepatitis C virus infection: relationship to
      histological and serum markers of hepatic fibrosis.
AB  - Endoglin, a transforming growth factor (TGF)-beta1 co-receptor, has been
      associated with renal and cutaneous fibrosis, as overexpression of this protein
      has been observed in biopsies from patients with glomerulosclerosis and
      scleroderma, respectively. Our aim was to evaluate whether endoglin may be
      associated with hepatic fibrosis featuring chronic hepatitis C virus (HCV)
      infection. Fifty-two anti-HCV+ patients, five anti-HCV- patients and 27 healthy
      subjects were studied. Western blot and immunohistochemistry were used to
      quantify the expression levels of endoglin and TGF-beta1 in liver biopsy samples,
      and serum concentrations of endoglin and hyaluronic acid were determined by
      enzyme-linked immunosorbent assays (ELISAs). In patients with advanced fibrosis,
      intrahepatic expression levels of endoglin and TGF-beta1 were significantly
      higher than those in patients with early fibrosis (mean: 3- and 5.8-fold,
      respectively) and normal liver (mean: 3.9- and 12-fold, respectively).
      Interestingly, activated hepatic stellate cells as well as portal and septal
      myofibroblasts expressed endoglin. Serum levels of endoglin were also
      significantly higher in patients with advanced fibrosis than in those with early
      fibrosis (55.5 +/- 1.6 vs 47.5 +/- 0.9 ng/mL, P < 0.001), showing a positive
      correlation with serum hyaluronic acid concentrations (r = 0.57, P = 0.01). In
      conclusion, increased intrahepatic endoglin and TGF-beta1 expression is
      significantly associated with progressive hepatic fibrosis in chronic HCV
      infection. Circulating endoglin levels are elevated in HCV patients showing a
      significant correlation with histological and serum markers of hepatic fibrosis.
      These data suggest an active role for endoglin in the fibrotic process featuring
      chronic HCV infection.

PMID- 16907851
TI  - Low density lipoprotein receptor transcripts correlates with liver hepatitis C
      virus RNA in patients with alcohol consumption.
AB  - Alcohol consumption has a major impact on the natural history of chronic
      hepatitis C virus (HCV) infection, although the underlying mechanisms are still
      debated. We designed a clinical study to evaluate the impact of alcohol abuse on
      both viral load and expression of low-density lipoprotein receptor (LDLR) and
      CD81 expression. Thirty-eight consecutive HCV-infected patients were enrolled.
      Group 1 (n = 18), < or =10 g alcohol/day, group 2 (n = 8), < or =30 g
      alcohol/day, group 3 (n = 12), >or =30 g alcohol/day. Receptors expression was
      measured by flow cytometry analysis in peripheral blood mononuclear cells (PBMC)
      and by specific real-time retrotranscription polymerase chain reaction (RT-PCR)
      in the liver. Serum viral load was evaluated by quantification of both HCV
      genomic RNA and total core antigen. The hepatic viral load was assessed by real
      time RT-PCR. Serum HCV-RNA and total core antigen were significantly correlated,
      and were higher, albeit not significantly, in group 3 than in group 1. Alcohol
      consumption had no effect on expression of HCV putative receptors in PBMC, except
      for CD81, which was upregulated on monocytes in group 2. In the liver, viral load
      and levels of LDLR transcripts were significantly higher in group 3 than in group
      1. Remarkably, a significant positive correlation was found between LDLR
      transcripts and HCV-RNA (r2 = 0.83, P < 10(-3)). Finally, in vitro experiments
      suggested that the effect of ethanol on LDLR expression was indirectly mediated
      by both tumour necrosis factor-alpha and interleukin-1beta. In conclusion, this
      study is the first to support a role for LDLR in the natural infection by HCV in
      man.

PMID- 16907853
TI  - Effect of adamantylamide dipeptide as adjuvant therapy to praziquantel in mice
      infected with different S. mansoni isolates.
AB  - This work investigated the possible use of AdDP as adjuvant therapy to
      praziquantel (PZQ) in mice infected with PZQ-insusceptible Schistosoma mansoni
      isolate in a trial to increase the susceptibility of this isolate to the drug.
      Two batches of C57 BL/6 mice were infected with PZQ-susceptible and 
      insusceptible S. mansoni isolates, and each batch was divided into five groups.
      Seven weeks postinfection, the experimental group received AdDP (5 mg/kg) in
      addition to PZQ in reduced dose (3x100 mg/kg). Three of the remaining four groups
      were treated controls; they received AdDP, PZQ in reduced dose and in full dose
      (2x500 mg/kg), and the fourth group was infected untreated. In mice infected with
      PZQ-susceptible or -insusceptible S. mansoni isolate, praziquantel alone, and in
      addition to AdDP, reduced worm and egg loads and increased percentage dead eggs.
      Also, they improved the histopathological changes (reduction in granuloma
      diameter, percentage fibrotic area with increased percentage degenerated eggs).
      Inducible nitric oxide synthase (iNOS), nitric oxide (NO) in culture of
      peritoneal macrophages, and number of CD68-positive cells were decreased with
      improved alanine amino transaminase. In mice receiving combined therapy AdDP+PZQ,
      the antischistosomal efficacy and the reductions in the inflammatory
      granulomatous reactions, NO in cultured peritoneal macrophages, percentage
      fibrotic areas recorded, were comparable to that in mice receiving full dose of
      PZQ, with significantly higher reduction in CD68 cells denoting enhanced
      antischistosomal efficacy and healing of the inflammatory reactions in the liver.

PMID- 16907854
TI  - Role of ultrasound-guided core biopsy in the evaluation of spleen pathology.
AB  - Core biopsy has not traditionally been recommended in the study of spleen nodules
      due to the supposed fragility of this organ leading to a high risk of post-core
      biopsy complications. A total of 13 patients who presented solid spleen nodules,
      diffuse splenomegaly, or both on imaging studies (CT, MR, US) were biopsied under
      ultrasound control with 18G BioPince needles. Cytological (imprints and
      cytocentrifugates) and histological material were obtained for diagnosis in every
      case. Malignant lymphomas were the most commonly found pathology (four diffuse
      large B-cell lymphomas, two follicular lymphomas, one Hodgkin's disease, one B
      cell lymphoma, NOS). In addition, there was one littoral-cell angioma, one well
      differentiated neuroendocrine carcinoma, metastatic, and one haemangioma. The
      remaining two cases showed congestive features, and supposed spleen involvement
      by lymphoma in one of them was ruled out. On follow up, there were no
      complications related to the core biopsy. Splenectomy was performed in six cases,
      two diagnostic and four therapeutic. We conclude that core biopsy is a safe and
      efficient method in the diagnosis of spleen nodules that could be considered in
      the routine diagnostic algorithm of these lesions.

PMID- 16907855
TI  - Diagnosis of Chlamydia trachomatis in Russia--in-house PCR assays may be
      effective but overall optimization and quality assurance are urgently needed.
AB  - In the present study, the performance of the cell culture method, two non-Russian
      direct immunofluorescence (DIF) assays, and three different in-house polymerase
      chain reaction (PCR) tests used in St. Petersburg, Russia, for detection of
      Chlamydia trachomatis in urogenital specimens was evaluated. A total of 650
      patients were examined and it was most disquieting that previous C. trachomatis
      positivity with Russian DIF assays could - 7 days later - be confirmed only in
      26% of the women and 30% of the men. Overall, the highest diagnostic sensitivity
      was obtained using PCR analysis. However, the sensitivity varied significantly:
      from 79% to 100% between the different PCR assays, sex of the patients, and type
      of samples. The highest sensitivity was obtained for female vaginal and male
      urine samples (100%). The specificity of the PCR assays varied from 97% to 100%.
      The sensitivity of cell culture and both the examined DIF assays was low, i.e. it
      varied from 46% to 56% and 55% to 75%, respectively. Meanwhile, cell culture was
      100% specific and the DIFs showed a specificity varying from 99% to 100%. In
      conclusion, in a Russian perspective, adequate in-house PCR methods may be used
      quite effectively for detection of C. trachomatis in invasive as well as non
      invasive clinical material. Simultaneous analysis of two different specimens from
      women resulted in a significantly increased detection rate of C. trachomatis.
      Nevertheless, in Russia the need for optimization and quality assurance of
      diagnostic methods for C. trachomatis, especially Russian DIF assays, has to be
      emphasized.

PMID- 16907856
TI  - Expression profiling of apoptosis-related genes in enterocytes isolated from
      patients with ulcerative colitis.
AB  - Apoptosis regulation has been implicated as a main cause of epithelial
      dysfunction in patients with ulcerative colitis. Apoptosis can be divided into
      distinct pathways, which depend on the expression of a large number of apoptosis
      related genes. The aim was to elucidate which pathways are dominant in normal and
      inflamed colonic epithelial cells. An apoptosis-specific gene array expression
      profiling system of 96 genes was used to determine the expression profile of
      apoptosis-related genes. Epithelial cells isolated from three patients with
      active ulcerative colitis were pooled and compared to pooled epithelial cells
      isolated from three control subjects. Genes found to be three-fold or more
      overexpressed in ulcerative colitis were subsequently analysed by PCR in a larger
      population (10 patients with ulcerative colitis, 8 control subjects). Selected
      genes found not to be regulated were additionally tested by PCR in the same
      population. Six genes were found to be highly expressed in epithelial cells from
      both controls and ulcerative colitis patients. These included Bcl-2
      antagonist/killer, B lymphoid tyrosine kinase, caspase 14, Harakiri, tumour
      necrosis factor (TNF) receptor 2, and TNF receptor-associated factor 1 (TRAF1).
      Three genes were found to be upregulated in ulcerative colitis (p<0.01): caspase
      1 and 5, and inhibitor of apoptosis protein 2 (c-IAP2). Both receptor- and
      mitochondrion-dependent apoptosis pathways are well expressed in enterocytes.
      Mainly activation-dependent and cytoprotective genes were upregulated in
      ulcerative colitis.

PMID- 16907857
TI  - Pin1 gene mutation is a rare event in gastric cancer.
AB  - The peptidyl-prolyl isomerase Pin1 is strikingly overexpressed in human cancers
      and is a novel regulator of beta-catenin. To determine whether somatic mutation
      of the Pin1 gene is involved in the development and/or progression of gastric
      cancer, we searched for mutations of the Pin1 gene in 95 gastric cancer
      specimens. The effect of Pin1 on beta-catenin expression was further examined in
      wild- and mutant-type Pin1-transfected HEK 293T cells. We found only one missense
      mutation that led to the substitution of alanine by aspartic acid at codon 118 of
      the Pin1 gene. On transfection study, the mutant Pin1 showed an increased
      expression of beta-catenin. However, the mutation had no effect on expression of
      the Pin1 protein in the case with Pin1 mutation. These results suggest that Pin1
      may not play a role in the development or progression of gastric cancer.

PMID- 16907859
TI  - Immunohistochemical staining patterns using epitope-specific antibodies indicate
      conformation variants of antisecretory factor/S5a in the CNS.
AB  - Antisecretory factor (AF/S5a/Rpn10) was originally identified through its ability
      to counteract pathological secretion. AF is also a potent anti-inflammatory
      agent, a neuromodulator, and an important component of the proteasome. Human AF
      has a calculated molecular mass of 41 kDa and a pI of 4.7. No family of AF-like
      proteins has been identified. AF has multiple functions in the cell, and
      different functional forms could exist as a result of post-translational
      modifications. Epitope-specific antibodies covering the entire length of AF were
      used to investigate whether modified forms of AF could be detected in the porcine
      spinal cord by Western blots, 2D gels, and immunohistochemistry (IHC). Western
      blot and 2D gels showed that all antisera detected a single protein with very
      similar molecular mass and pI. However, IHC resulted in an epitope-specific
      subcellular staining pattern. Antisera recognizing epitopes in the N-terminal
      part of AF, containing the antisecretory activity, showed a more restricted
      localisation than antisera directed at the C-terminal part, containing the
      ubiquitin-binding sites. We suggest that AF can exist in several conformational
      variants, perhaps due to differences in redox state and/or pH in the various
      cellular compartments. Such conformational changes could be of functional
      importance.

PMID- 16907858
TI  - Effect of exposure to fluoroquinolones and beta-lactams on the in vitro activity
      of other groups of antibiotics in Salmonella spp.
AB  - After designing in vitro models of repeated exposure of Salmonella spp. to
      various beta-lactams and fluoroquinolones we studied the decrease in
      susceptibility to other antibiotic families of the mutants generated. There was a
      decrease in the susceptibility of all the mutants to tetracycline, cotrimoxazole
      and chloramphenicol. Mutants generated following exposure to fluoroquinolones
      showed reduced susceptibility to amoxicillin, amoxicillin/clavulanic acid,
      cefoxitin and cefuroxime, whereas mutants generated following beta-lactam
      exposure showed reduced susceptibility to nalidixic acid and ciprofloxacin. We
      observed that the efflux pump systems are activated in the mutants generated and
      this may therefore be the cause of the decrease in susceptibility. In many cases
      the decrease is small and is not detected if the CLSI criteria are applied.
      Nevertheless, more detailed studies should be done to evaluate the importance of
      this phenomenon and rationalize the use of antibiotics in both humans and animals
      so as to control the increase in the number of multiresistant strains.

PMID- 16907860
TI  - Differential gene expression of GDP-L-fucose-synthesizing enzymes, GDP-fucose
      transporter and fucosyltransferase VII.
AB  - L-fucose is a fundamental monosaccharide component of many mammalian
      glycoproteins and glycolipids. Fucosylation requires GDP-L-fucose as a donor of
      fucose and a specific fucosyltransferase (Fuc-T) to catalyze the transfer of L
      fucose to various lactosamine acceptor molecules. The biosynthesis of GDP-L
      fucose consists of two pathways. The constitutively active de novo pathway
      involves conversion of cellular GDP-D-mannose to GDP-L-fucose by GDP-D-mannose
      4,6-dehydratase (GMD) and GDP-4-keto-6-deoxy-D-mannose-3,5-epimerase-4-reductase
      (FX). In the alternative biosynthetic pathway, in the salvage metabolism, L
      fucokinase (Fuk) synthesizes L-fucose-1-phosphate from free fucose. L-fucose-1
      phosphate is further catalyzed to GDP-L-fucose by GDP-L-fucose pyrophosphorylase
      (Fpgt). GDP-L-fucose, synthesized in the cytosol, is translocated to the Golgi
      for fucosylation by a specific GDP-fucose transporter (FUCT1). Glycans that
      contain alpha(1,3)-fucosylated modifications, e.g. sialyl Lewis X-type glycans,
      have an important role in inflammation and in tumorigenesis. We studied the mRNA
      expression levels of GDP-L-fucose-synthesizing enzymes, GDP-fucose transporter
      and fucosyltransferase VII by quantitative real-time PCR in mouse endothelial
      cells, macrophages and lymphoid tumor cells. Moreover, the expression of the same
      transcripts was detected in acute inflammation using rat kidney allograft as
      model system. Our results indicate the simultaneous upregulation of the GDP-L
      fucose synthesizing enzymes of the de novo pathway, GDP-fucose transporter and
      fucosyltransferase VII in inflammation and in tumorigenesis.

PMID- 16907862
TI  - Symptomatic adenomyoma of the Vaterian system: a pathologic curiosity with a
      potential for misdiagnosis.

PMID- 16907861
TI  - CDH1 (E-cadherin) in testicular germ cell neoplasia: suppressed translation of
      mRNA in pre-invasive carcinoma in situ but increased protein levels in advanced
      tumours.
AB  - E-cadherin (CDH1) is a transmembrane glycoprotein involved in cellular adhesion.
      In our recent microarray studies of testicular germ cell tumours (TGCTs) and the
      common precursor carcinoma in situ (CIS), CDH1 mRNA was highly expressed in CIS
      and embryonal carcinoma. It has previously been reported that the CDH1 protein is
      not expressed in CIS. To resolve the discrepancy, we performed a detailed
      analysis of the expression of CDH1 mRNA and protein in a series of normal and
      neoplastic testes. High expression of CDH1 mRNA in CIS was confirmed by real-time
      PCR and in situ hybridisation. At the protein level, however, CDH1 was only
      detected with one of three tested antibodies, but Western blotting analysis with
      this antibody showed additional bands, suggesting unspecific staining. The levels
      of a CDH1 protein fragment in serum samples from 58 patients with TGCTs were
      analysed by ELISA; we found significantly higher levels in patients with advanced
      disease (stage II/III) when compared to healthy individuals and patients with
      stage I TGCT. In conclusion, despite high mRNA levels, the CDH1 protein is not
      expressed in CIS, suggesting translational suppression of CDH1 protein
      expression. CDH1 serum levels may be a serological marker for staging of TGCT
      patients.

PMID- 16907863
TI  - Vulvar keratoacanthoma.
AB  - A keratoacanthoma of the vulva in a 33-year-old woman is described. The patient
      presented with a rapidly growing exophytic lesion of 1 cm in diameter over the
      clitoris that had been present for a couple of months. An excisional biopsy was
      performed. Pathologic examination of the exophytic nodule showed squamous
      proliferation with a characteristic central keratin- filled crater. There were
      pushing margins. High power microscopy showed squamous cells of cytologically
      bland appearance with glassy cytoplasm. There were few mitotic figures. Less than
      10% Ki-67-positive staining nuclei were seen. There was no p53 oncoprotein
      overexpression. Keratoacanthoma of the vulva is rare with only five cases having
      been reviewed in the English literature since 1985. Keratoacanthomas are rapidly
      growing crateriform lesions on the sun-exposed skin of the elderly. Because of
      its rarity in the vulva, the lesion can be misinterpreted as a malignant lesion
      such as squamous cell carcinoma. Awareness of vulvar occurrence of
      keratoacanthoma and its characteristic histopathologic features will help avoid
      misdiagnosis of a squamous cell carcinoma leading to radical surgery.

PMID- 16907864
TI  - Detection of Dirofilaria (Nochtiella) repens DNA by polymerase chain reaction in
      embedded paraffin tissues from two human pulmonary locations.
AB  - We here report two new cases of human pulmonary dirofilariasis in men aged 62 and
      64 from Northern and Central Italy, respectively. Both were asymptomatic and the
      infections were discovered incidentally when chest radiographs taken for another
      reason revealed the presence of a coin lesion. The initial clinical diagnosis was
      oriented towards a lung tumour, and an excisional lung biopsy after thoracotomy
      was necessary for the final diagnosis. Pathologically, the lesion consisted of a
      roundish subpleural infarct with a central thrombotic artery containing sections
      of an immature nematode: Dirofilaria repens was diagnosed histologically in one
      case, the necrotic condition of the worm allowing only genus identification,
      Dirofilaria, in the other case. In both samples, PCR analysis amplified a 246 bp
      product, specific for the IpS insert 11 of D. repens. The authors stress the role
      of PCR in the diagnosis of this parasite from paraffin samples, also in cases in
      which identification of the species was not possible by conventional morphology
      due to poor conservation of the worm. These cases represent the first PCR-based
      diagnosis of D. repens in a human pulmonary dirofilariasis on samples embedded in
      paraffin.

PMID- 16907865
TI  - Primary peritoneal carcinoma: a rare neoplasm with pleomorphic trophoblastic
      morphology.
AB  - We report a case of primary peritoneal carcinoma with trophoblastic morphology in
      a 78-year-old woman, diagnosed by histological and immunohistochemical analysis
      of surgically resected specimens, including the omentum and part of the small
      bowel. Microscopically, the resected specimens showed diffuse infiltration of a
      poorly differentiated tumor. Numerous large, often multinucleated cells were
      seen, and mitotic figures were frequent. Immunohistochemical staining showed a
      positive reaction for most cytokeratins, EP4, EMA, CA-125, Glut1, WT1, beta-hCG
      and PLAP. We reached a diagnosis of primary peritoneal carcinoma with
      trophoblastic morphology. To our knowledge this morphology of a primary
      peritoneal carcinoma has not been described previously.

PMID- 16907866
TI  - Osteosarcoma arising in the breast.
AB  - We report on a 49-year-old woman with osteosarcoma arising in the breast. She had
      undergone two consecutive excision biopsies for right breast tumors at ages 40
      and 42 years. The tumors were diagnosed as a fibroadenoma and a benign phyllodes
      tumor, respectively. At age 46 years, she noticed a gradually enlarging mass in
      the same breast. After 3 years, at age 49 years, total mastectomy was performed.
      The tumor occupied the entire breast and measured 12x9x8.5 cm. The tumor cells
      were spindle-shaped and pleomorphic, with large, irregular nuclei and distinct
      nucleoli. Many tumor cells had characteristics of osteoblastic and chondroblastic
      elements producing osteoid, osseous, and cartilaginous intracellular substances.
      Pathologic mitoses and apoptotic cells were frequent. Neoplastic cells had
      infiltrated the skin. Blood and lymph vessel invasion was present. Tumor cells
      expressed vimentin, osteopontin, vascular endothelial growth factor, CD10, and
      alkaline phosphatase, but did not express keratin. Chemotherapy was not
      effective. The patient died of multiple pulmonary metastases 9 months after
      mastectomy.

PMID- 16907867
TI  - Professor Robin Coombs FRS (1921-2006).

PMID- 16907869
TI  - Transfusion recipient identification.
AB  - Recent reports from different haemovigilance systems indicate that errors in the
      whole-blood transfusion chain - from initial recipient identification to final
      blood administration - occur with a frequency of approximately 1 in 1000 events.
      Although mistakes occur also within the blood transfusion service, about two
      thirds of errors are associated with incorrect blood recipient identification at
      the patient's bedside. To prevent the potentially fatal consequences of such
      mistakes, specific tools have been developed, including patient identification
      bracelets with barcodes and/or radio frequency identification devices, mechanical
      or electronic locks preventing access to bags assigned to other patients, and
      palm computers suitable for transferring blood request and administration data
      from the patient's bedside to the blood transfusion service information system in
      real time. The effectiveness of these systems in preventing mistransfusion has
      been demonstrated in a number of studies.

PMID- 16907870
TI  - Current status of oxygen carriers ('blood substitutes'): 2006.
AB  - An alternative to blood transfusion, based on oxygen-carrying solutions, has been
      sought for over a century. The present 'first-generation' haemoglobin-products
      were based on observations that crosslinking with, for example, glutaraldehyde,
      overcame subunit dissociation and renal toxicity. Experience with these solutions
      has shown that they can be vasoactive, sometimes increasing blood pressure,
      sometimes decreasing tissue perfusion and sometimes both. Clinical trials have
      been disappointing because of unexpected toxicity. The 'second-generation'
      products are based on a better understanding of the mechanisms of this
      vasoconstriction. Such products may seem counterintuitive by traditional
      standards, but it is hoped that they will be less toxic, more beneficial to
      patients, and more economical to produce.

PMID- 16907871
TI  - Differential sensitivities of pathogens in red cell concentrates to Tri-P(4)
      photoinactivation.
AB  - BACKGROUND AND OBJECTIVES: Photodynamic treatment (PDT) with the cationic
      porphyrin, mono-phenyl-tri-(N-methyl-4-pyridyl)-porphyrin chloride [Tri-P(4)],
      has previously been shown to be effective at inactivating vesicle stomatitis
      virus (VSV) in red cell concentrates (RCC) with limited damage to red blood cells
      (RBC). The aim of this study was to determine the pathogen-inactivating capacity
      of PDT with Tri-P(4) for a broader range of pathogens and to establish the
      associated effect on in vitro RBC quality. MATERIALS AND METHODS: A series of
      viruses and bacteria was spiked into 60% RCC. Pathogen inactivation was
      determined after PDT with 25 microm Tri-P(4) and red light up to 360 kJ/m2. Human
      immunodeficiency virus (HIV)-infected cells were evaluated for cell death
      induction, and RCC were analysed for the induction of haemolysis and ATP content.
      RESULTS: For the lipid-enveloped viruses bovine viral diarrhoea virus, HIV and
      pseudorabies virus, and for the Gram positive bacterium, Staphylococcus aureus,
      and the Gram-negative bacteria, Pseudomonas aeruginosa and Yersinia enterolitica,
      inactivation of > or = 5 log10 was measured after 60 min of PDT with Tri-P(4).
      The required treatment time to achieve this level of inactivation was four times
      longer than required for VSV. For cell-associated HIV, only 1.7 log10 of
      inactivation was found, despite clear induction of cell death of HIV-infected
      cells. The non-enveloped virus, canine parvovirus, was completely resistant to
      the treatment. PDT of RCC with Tri-P(4) for 60 min, and subsequent storage in AS
      3, resulted in 4% haemolysis after 35 days of storage. The ATP content of
      untreated and treated RBC declined with similar kinetics during storage.
      CONCLUSION: PDT of RCC with Tri-P(4) for 60 min inactivates a wide range of
      pathogens, but not cell-associated HIV and a non-enveloped virus, and compromises
      RBC quality. This reduces the suitability of PDT with Tri-P(4) for red cell
      sterilization. Therefore, further improvements in the treatment procedures to
      potentiate pathogen inactivation and to preserve RBC integrity will be required
      to generate an effective treatment for sterilizing RCC.

PMID- 16907872
TI  - Implementation of a 20-nm pore-size filter in the plasma-derived factor VIII
      manufacturing process.
AB  - BACKGROUND AND OBJECTIVES: Virus inactivation and removal are important
      prerequisites to ensure the safety of plasma derivatives. For virus inactivation
      and removal in our coagulation factor VIII (FVIII) product, CROSS EIGHT M, the
      production process consists of solvent-detergent (S/D) treatment, two
      chromatography steps and virus filtration with a 35-nm pore-size filter. However,
      the clearance of non-enveloped viruses was not as good as that of enveloped
      viruses because non-enveloped viruses are resistant to S/D treatment and are too
      small to be removed by the filter. In this study, in order to improve the viral
      safety of the FVIII products, we attempted to replace the 35-nm pore-size virus
      filter with a 20-nm filter. MATERIALS AND METHODS: The virus-filtration process
      was validated for the removal of enveloped and non-enveloped model viruses.
      Several factors that might affect the FVIII yield on filtration were investigated
      to obtain a higher recovery. The biochemical properties of the FVIII products
      produced with the 20-nm pore-size filter were compared with those produced by the
      35-nm filter. RESULTS: Virus filters of 20-nm pore size effectively removed the
      small non-enveloped viruses when compared with the 35-nm pore-size virus filter.
      The permeability of FVIII through the 20-nm pore-size filter was inversely
      proportional to the concentration of FVIII at filtration, and directly
      proportional to the amount of postfiltration solution. No differences were
      observed in the biochemical properties of both FVIII products, such as the
      structure and stability of the FVIII, the contents and multimeric structure of
      von Willebrand factor (vWF), and FVIII activation by thrombin. CONCLUSIONS: The
      virus-clearance efficiency of the FVIII product, CROSS EIGHT M, was markedly
      increased, in particular against small non-enveloped viruses, by changing the
      virus filter pore size from 35 nm to 20 nm. It was possible to implement the 20
      nm pore-size filter without variation of the biochemical properties or a serious
      loss of FVIII.

PMID- 16907873
TI  - Accurate prediction of autologous stem cell apheresis yields using a double
      variable-dependent method assures systematic efficiency control of continuous
      flow collection procedures.
AB  - BACKGROUND AND OBJECTIVES: Stem cell collection is a standard procedure for the
      procurement of autologous grafts to rescue myelosuppression induced by high-dose
      treatments. Accurate prediction of collection yields may contribute to optimize
      planning and quality control of collection. MATERIALS AND METHODS: Data of 313
      autologous haematopoietic stem cell (AHSC) evaluable collections performed in 208
      patients with haematologic and non-haematologic neoplasms from seven centres were
      prospectively analysed to test the accuracy of yield predictions generated by a
      formula that required the input of peripheral blood (PB) CD34+ cell precount and
      desired PB volume to be processed. Data were matched in a standard linear
      regression, in a zero-point regression analysis and tested for prediction
      accuracy. Further 165 AHSC collections were analysed on a single-centre basis,
      using yield predictions as reference standards. RESULTS: Analysis showed high
      levels of correlation between measured collection yields (my) and predictions
      (py) (R = 0.85; P = 0.000000) as well as high degree of prediction accuracy (my
      vs. py at paired t-test: P = 0.114781; median my/py ratio = 1.23). Analysis of
      additional 165 AHSC collections on a single-centre basis showed that the analysed
      centres had 70% or more measured yields comprising the 0.6-1.8 interval of the
      my/py ratio. The observance of the 'efficiency' my/py interval assured collection
      quality control in these centres confirming the reliability of the method.
      CONCLUSIONS: This prediction method generates accurate and immediate yield
      predictions allowing collection planning and rapid efficiency control. As a
      consequence of our study, four centres out of seven use the described method to
      plan both leukapheresis number and single-procedure blood processing volume while
      the remaining three centres plan leukapheresis number on the basis of our
      predictions, maintaining a fixed single-procedure 200 ml/kg blood volume
      processing, according to their centre AHSC collection policy.

PMID- 16907874
TI  - Platelet content and growth factor release in platelet-rich plasma: a comparison
      of four different systems.
AB  - BACKGROUND: Different systems for preparation of platelet-rich plasma are
      commercially available, but data for comparison of these systems have not been
      published so far. MATERIALS AND METHODS: We investigated the performance of
      Vivostat PRF Preparation Kit, PCCS Platelet Concentrate Collection System,
      Harvest SmartPReP 2 APC 60 Process, and Fibrinet Autologous Fibrin & Platelet
      System. The preparations provided by these systems are platelet concentrates with
      high numbers of platelets in a small volume of plasma and PDGF-AB is released
      continuously during the 5 days after preparation. RESULTS: Vivostat PRF
      Preparation Kit, PCCS Platelet Concentrate Collection System, Harvest SmartPReP 2
      APC 60 Process are comparable in platelet yield and total amount of released PDGF
      AB after 120 h while with Fibrinet the lowest platelet yield and PDGF-AB content
      of supernatant was achieved. The ability of growth factor release was equal in
      all four systems. CONCLUSION: In conclusion, all four systems for preparation of
      platelet-rich plasma investigated result in considerable growth factor release.
      In what extent the total content of PDGF-AB as a consequence of platelet yield
      has an impact on wound healing has to be further investigated.

PMID- 16907875
TI  - Development of permanent national register of blood component use utilizing
      electronic hospital information systems.
AB  - BACKGROUND AND OBJECTIVES: We wanted to establish a permanent national database
      system, which can be utilized to study transfusion recipients and blood use in
      Finland. MATERIALS AND METHODS: A regularly updated register for permanent use
      was developed. To study the usability of the database, years 2002 and 2003 were
      further analysed. Database included all transfused patients in major blood
      transfusing hospitals from four university and five central hospital districts
      managing altogether 63% of Finnish inpatient hospital episodes. RESULTS: Audit of
      gathered data reveal 96.8% match in adult blood components with Finnish Red
      Cross, Blood Service sales figures. Model data set includes 59,535 transfused
      patients (44.3% men and 55.7% women) having received 529,104 blood components.
      Half of all blood units were transfused in connection with surgical operations.
      Most of the blood recipients were elderly (51.6% are over 64 years of age). Blood
      component use and transfusion-related costs varied widely between hospitals.
      CONCLUSION: Hospital data managing systems can be useful for creating a
      population-based database system to monitor and compare transfusion practices.
      This record provides information about transfusion epidemiology for transfusion
      professionals, hospital management, and hospital administration.

PMID- 16907876
TI  - The effects of a treatment protocol for cardiac surgical patients with excessive
      blood loss on clinical outcomes.
AB  - BACKGROUND AND OBJECTIVES: Excessive blood loss (EBL) is a common complication of
      cardiac surgery that is associated with adverse events. The objective of this
      before/after study was to determine whether the implementation of a protocol for
      management of cardiac surgical patients with EBL was associated with improved
      clinical outcomes. MATERIALS AND METHODS: In November 2002, a protocol for prompt
      identification and aggressive management of cardiac surgical patients with EBL
      was implemented at our institution. The independent relationship between protocol
      implementation and adverse outcomes was measured by comparing the outcomes of
      patients who received > or = 4 RBC (red blood cell) units within 1 day of surgery
      and were operated on before protocol implementation (2000-02) with those operated
      on after protocol implementation (2003-05), using multivariable logistic
      regression analysis to control for the effects of confounders. The primary
      outcome was a composite of adverse events that included death, renal failure,
      stroke, and sepsis. Bootstrapping was used to confirm the validity of the
      results. RESULTS: Of the 11,314 patients who underwent surgery during the study
      period, 1875 (16.6%) received > or = 4 RBC units within 1 day of surgery, with
      958 and 917 in the pre- and postprotocol periods, respectively. The composite
      adverse outcome occurred in 164 (17.1%) patients in the preprotocol period and
      115 (12.5%) patients in the postprotocol period (P = 0.005). Protocol
      implementation was independently associated with reduced odds of the composite
      adverse outcome (odds ratio 0.67; 95% confidence interval 0.50, 0.91; P = 0.01).
      This estimate was stable in bootstrap sampling. CONCLUSION: Implementation of a
      protocol to manage EBL in cardiac surgery was independently associated with
      improved outcomes.

PMID- 16907877
TI  - Current perceptions of Canadian autologous blood donors.
AB  - BACKGROUND AND OBJECTIVES: We determined the perceptions and motivations of
      autologous donors to establish their regard for this process and the new blood
      system established in 1999 in Canada. MATERIALS AND METHODS: Patients were
      surveyed before and after orthopaedic, cardiac, urological or gynecological
      procedures. RESULTS: Patients (n = 100; 57 men and 43 women) ranged in age from
      19 to 83 years. Most had finished high school, and 21 had a university degree.
      Eighty-four had undergone previous surgery and 27 a previous transfusion. Fifty
      one had been blood donors and 17 had been autologous donors. Specialists
      suggested donation to 78 of the patients. Seventy-two participated because they
      knew that their blood would be there. Three had a mistrust of the blood provider.
      Sixty-six believed that there is still a risk of receiving contaminated blood.
      Sixty-nine thought any risk was > or = 1 in 100,000; however, 16 thought the risk
      was < 1 in 1000. Postsurgery, 83 were happy to have donated their blood and 77
      would do it again. Many felt that it improved their outcome. Most felt an
      increased sense of safety. Eighty-three patients were confident that the Canadian
      blood system had improved, but 17 were unsure. CONCLUSIONS: Concern about the
      safety of the allogeneic blood supply still drives the wish to autodonate. The
      process gives patients a sense of control and security. A large proportion of
      people felt that the Canadian blood system had improved, as determined by this
      2003 study.

PMID- 16907878
TI  - A prospective multicentre study on the safety of long-term intensive
      plasmapheresis in donors (SIPLA).
AB  - BACKGROUND AND OBJECTIVES: The safety of chronic intensive donor plasmapheresis
      has not been determined in large prospective studies examining dropout rates,
      dropout reasons and predictors of withdrawals. MATERIALS AND METHODS: Twenty-one
      plasma centres recruited 3783 donors who were switched from a moderate to an
      intensive plasmapheresis programme and observed over a 3-year period. Individuals
      weighing < 70 kg and > or = 70 kg donated 750 ml and 850 ml of plasma per
      session, respectively. The maximum of annual donations was limited to 60. Total
      serum protein (TSP) and haemoglobin (Hb) or haematocrit (Hct) were determined at
      each donation, and immunoglobulin G (IgG) at every fifth donation. Dropout rates,
      dropout reasons and potential predictors of withdrawal were analysed. RESULTS:
      Dropouts were predominantly due to socioeconomic (49.2% of all donors) or medical
      reasons not related to plasma donations (10.4% of all donors). Sixteen per cent
      of donors dropped out when IgG, TSP or Hb levels fell below threshold values.
      Severe clinical adverse events related to plasmapheresis were observed in five
      subjects. The incidence in severe cardiovascular diseases was lower in donors
      than in the general population. The risk factors that led to dropping out as a
      result of low IgG, TSP or Hb levels included younger age, female gender, low
      initial IgG levels and a high donation frequency. Neither body weight nor the
      amounts of plasma donated per kilogram of body weight per session were associated
      with ceasing due to medical reasons, whether related or unrelated to plasma
      donations. Females and males within the respective lowest body weight category
      were not at higher risk of dropping out. CONCLUSION: Long-term intensive donor
      plasmapheresis under conditions investigated in this study is safe. All donors
      weighing > or = 70 kg are safely able to donate 850 ml of plasma in each session
      up to 60 times per year, provided that they are carefully monitored.

PMID- 16907879
TI  - Monitoring survival and function of transfused platelets in Glanzmann
      thrombasthenia by flow cytometry and thrombelastography.
AB  - Patients with Glanzmann thrombasthenia (GT) may form isoantibodies which induce
      refractoriness or inhibition of function of transfused platelets. We monitored
      the survival and function of transfused platelets by flow cytometry and
      thrombelastography in a patient with GT. Gating on CD42a+ allowed identification
      of even a few transfused platelets. Only by gating on these CD41+ CD42a+ cells
      were we able to demonstrate their capability to bind fibrinogen and PAC-1 upon
      activation. Platelets were rapidly cleared from the circulation as a result of
      boosted isoantibodies. The contribution of transfused platelets to clot formation
      was also demonstrated by thrombelastography by blocking their function with
      abciximab.

PMID- 16907880
TI  - Photoinactivation of Leishmania donovani infantum in red cell suspensions by a
      flexible thiopyrylium sensitizer.
AB  - BACKGROUND AND OBJECTIVES: Leishmaniasis is a disease caused by protozoan
      parasites of the genus Leishmania, which are intracellular parasites of monocytes
      and macrophages. Transmission of the organism has been observed by transfusion of
      infected blood from asymptomatic donors to immunocompromised recipients, leading
      to clinically apparent disease. There is no licensed Leishmania screening test
      currently available. MATERIALS AND METHODS: This study investigated the potential
      for a novel DNA-intercalating photosensitizer, thiopyrylium (TP), to inactivate
      Leishmania donovani infantum in red cell (RBC) suspensions. RESULTS: A 5.7 TCID50
      reduction of Leishmania was observed in samples treated with 12.5 micromole l(-1)
      TP and 1.1 J cm(-2) light. CONCLUSIONS: Leishmania is highly sensitive to
      photoinactivation under conditions that have been previously demonstrated to
      maintain RBC properties during 42 days of storage.

PMID- 16907881
TI  - Delayed detectability of anti-HPA-3a by the MAIPA assay in a severe neonatal
      alloimmune thrombocytopenia, but successful transfusion of incompatible donor
      platelets: a case report.

PMID- 16907882
TI  - RHD DNA screening for weak D, DEL and D+/- 'chimeras'.

PMID- 16907883
TI  - Perioperative blood salvage.

PMID- 16907890
TI  - Clinical features, biochemical parameters, and virological profiles of patients
      with hepatocellular carcinoma in Hong Kong.
AB  - BACKGROUND: Clinical features of hepatocellular carcinoma patients are changing
      because of screening. AIM: To examine the clinical features of hepatocellular
      carcinoma patients in Hong Kong and validity of different staging systems.
      METHODS: A total of 223 Chinese patients with hepatocellular carcinoma were
      studied. RESULTS: Seventy-eight percent of hepatocellular carcinoma patients had
      chronic hepatitis B (43% diagnosed by screening). Hepatitis B positivity, weight
      loss, jaundice, encephalopathy, alpha-fetoprotein level, portal vein thrombosis,
      extrahepatic metastasis, and treatment were shown to be independent factors
      affecting survival. Of chronic hepatitis B patients, hepatitis B virus DNA levels
      (P = 0.001) and portal vein thrombosis (P = 0.008) were independent factors
      affecting survival. Seventy-six percent of chronic hepatitis B patients with
      hepatocellular carcinoma were hepatitis B e antigen negative. Screening patients
      had hepatocellular carcinoma detected at an earlier stage and better survival
      (median survival: 21 vs. 4 months, P < 0.0001). All staging systems had good
      stratification of survival. Prognosis and median survival generated were
      different when compared with the US data. CONCLUSIONS: Chronic hepatitis B was
      the most common cause of hepatocellular carcinoma in Hong Kong. High-risk chronic
      hepatitis B patients should be followed irrespective of the hepatitis B e antigen
      status. Hepatitis B virus DNA levels at the time of diagnosis are an important
      survival predictor. Screening detected hepatocellular carcinoma at an earlier
      stage and prolonged survival. Staging systems should be validated in different
      populations.

PMID- 16907891
TI  - Rates and predictors of hepatitis C virus treatment in HCV-HIV-coinfected
      subjects.
AB  - BACKGROUND: True treatment rates and the impact of comorbidities on treatment
      rates for hepatitis C virus in the HCV-HIV-coinfected subjects are unknown. AIM:
      To quantify the rates of treatment prescription and the effect of comorbidities
      on hepatitis C virus treatment rates in HCV-HIV-coinfected veterans. METHODS: The
      Veterans Affairs National Patient Care Database was used to identify all
      hepatitis C virus-infected subjects between 1999 and 2003 using ICD-9 codes.
      Demographics, comorbidities and pharmacy data were retrieved. We used logistic
      regression to compare the predictors of hepatitis C virus treatment in hepatitis
      C virus-monoinfected and HCV-HIV-coinfected subjects. FINDINGS: We identified 120
      507 hepatitis C virus-infected subjects, of which 6502 were HIV coinfected. 12%
      of the hepatitis C virus-monoinfected and 7% of the -coinfected subjects were
      prescribed hepatitis C virus treatment (P < 0.0001). Those not prescribed
      treatment were older (48.6 years vs. 47.7 years, P = 0.007) and more likely to be
      black (52% vs. 32%, P < 0.0001). HIV coinfected was less likely to be prescribed
      hepatitis C virus treatment (OR 0.74, 95% CI: 0.67-0.82). Among the coinfected
      subjects, the following were associated with non-treatment (OR, 95% CI): black
      race (0.45, 0.35-0.57); Hispanic race (0.56, 0.38-0.82); drug use (0.68, 0.53
      0.88); anaemia (0.17, 0.11-0.26); bipolar disorder (0.63, 0.40-0.99); major
      depression (0.72, 0.53-0.99); mild depression (0.47, 0.35-0.62). CONCLUSIONS: A
      small number of HCV-HIV-coinfected veterans are prescribed treatment for
      hepatitis C virus. Non-treatment is associated with increasing age, minority
      race, drug use and psychiatric illness. Further studies are needed to determine
      the eligibility for treatment and reasons for non-treatment for hepatitis C
      virus.

PMID- 16907892
TI  - Effectiveness of interferon plus ribavirin combination in the treatment of naive
      patients with hepatitis C virus type 5. A French multicentre retrospective study.
AB  - AIM: To assess the rate of sustained virological response in naive hepatitis C
      virus-type 5 patients treated by standard interferon or pegylated-interferon
      [corrected] (peg-interferon) and ribavirin combination for 48 weeks. PATIENTS AND
      METHODS: A total of 87 hepatitis C virus patients were included from 12 centres
      in France; 28 patients received interferon plus ribavirin and 59 were treated
      with peg-interferon plus ribavirin. RESULTS: Baseline characteristics were: mean
      age 58 +/- 11 years, sex ratio 1, 66% had metavir fibrosis score >or=F2, 21% were
      cirrhotics and 53% had pretherapeutic viral load >or=800,000 IU/mL. Sustained
      virological response was achieved in 64% and 58% of hepatitis C virus-5 patients
      treated with interferon and peg-interferon, respectively (NS). In adherent
      patients, sustained virological response was obtained in 75% of patients.
      Sustained virological response in hepatitis C virus-5 patients (60%) was
      significantly higher than sustained virological response in hepatitis C virus-1
      patients (37%) (P = 0.0499) and not significantly different from sustained
      virological response in hepatitis C virus-2-3 patients (63%) (P = 0.8098).
      CONCLUSIONS: Combination therapy is effective in 60% of hepatitis C virus-5
      infected patients. Sustained virological response seems better in hepatitis C
      virus-5 patients than in hepatitis C virus-1 patients, and is similar to that of
      hepatitis C virus-2-3 patients. More studies are needed to determine optimal
      duration of treatment in hepatitis C virus-5 patients.

PMID- 16907893
TI  - Proton pump inhibitor therapy is a risk factor for Clostridium difficile
      associated diarrhoea.
AB  - BACKGROUND: Inhibition of gastric acid removes a defence against ingested
      bacteria and spores, increasing the risk of some forms of gastroenteritis.
      Previous studies investigating a possible link between acid suppression therapy
      and Clostridium difficile-associated diarrhoea have reported conflicting results.
      AIM: To investigate whether acid suppression therapy is associated with an
      increased risk of C. difficile-associated diarrhoea. Prospective case-control
      study of 155 consecutive in-patients with C. difficile-associated diarrhoea.
      RESULTS: Antibiotics had been received by 143 (92%) of the C. difficile
      associated diarrhoea group and 76 (50%) of the controls during the preceding 3
      months. Among those receiving antibiotics, 59 (41%) of the C. difficile
      associated diarrhoea group had also received acid suppression, compared with 21
      (28%) of controls (OR 1.84, CI 1.01, 3.36, chi(2) = 4.0, P = 0.046). Among the
      entire C. difficile-associated diarrhoea group 64 (41%) had received acid
      suppression compared with 40 (26%) of controls (OR 1.99, CI 1.19, 3.31, chi(2) =
      7.9, P = 0.005). Logistic regression analyses found that C. difficile-associated
      diarrhoea was independently associated with: antibiotic use (OR 13.1, 95% CI:
      6.6, 26.1); acid suppression therapy (OR 1.90, 95% CI: 1.10, 3.29); and female
      sex (OR 1.79, 95% CI: 1.06, 3.04). CONCLUSIONS: The risk of C. difficile
      associated diarrhoea in hospitalized patients receiving antibiotics may be
      compounded by exposure to proton pump inhibitor therapy.

PMID- 16907894
TI  - Antireflux surgery for non-erosive and erosive reflux disease in community
      practice.
AB  - BACKGROUND: Antireflux surgery has been mainly evaluated in tertiary referral
      centres. Data regarding post-operative outcome in non-erosive reflux disease are
      lacking. AIM: To assess long-term outcome after antireflux surgery performed in a
      community practice setting. METHODS: We selected consecutively 60 non-erosive
      reflux disease patients and 61 erosive oesophagitis patients with symptomatic
      gastro-oesophageal reflux disease. After surgery, each subject answered a
      validated disease-specific health-related quality of life questionnaire and
      another questionnaire focusing on symptoms, late morbidity and drug use. RESULTS:
      After a 43-month median follow-up, an excellent outcome was reported by less than
      two-thirds of patients. Quality of life scores were lower in the non-erosive
      reflux disease group, especially in female patients. Non-erosive reflux disease
      patients reported more daily symptoms and more reflux-related symptoms (P =
      0.04). Proton-pump inhibitor use was higher in non-erosive reflux disease
      patients (P < 0.005). Multivariate analysis identified four independent
      predictive factors associated with better outcome, namely male gender, abnormal
      preoperative acid exposure, a long duration of symptoms and surgical expertise.
      CONCLUSIONS: In community practice, the results of antireflux surgery are
      inferior to those reported by tertiary centres. Outcome seems poorer in non
      erosive reflux disease especially in female patients. Nearly one-third of the non
      erosive reflux disease patients continue to take proton-pump inhibitors. These
      results highlight the need for careful selection of patients before antireflux
      surgery.

PMID- 16907895
TI  - Clinical outcome in upper gastrointestinal bleeding complicating low-dose aspirin
      and antithrombotic drugs.
AB  - BACKGROUND: The current risk stratification systems in upper gastrointestinal
      bleeding do not correct for the intake of low-dose aspirin and other
      antithrombotic drugs. AIM: To test the Blatchford scores in evaluating the
      clinical outcome in bleeders using these drugs. METHODS: We calculated the
      Blatchford scores in 510 bleeders, including 123 on low-dose aspirin, 44 on other
      antithrombotic drugs, and 68 on non-steroidal anti-inflammatory drugs. RESULTS:
      The median clinical scores distributed according to aetiological risk factors
      were as follows: no risk factors, 5; non-steroidal anti-inflammatory drugs, 8;
      aspirin, 7; other antithrombotics, 6; excess alcohol, 4; multiple risk factors,
      7; (P = 0.003, Kruskal-Wallis test). Scores correlated positively with the
      duration of admission in the entire group (r(s) = 0.285; P < 0.001) and in those
      taking aspirin and antithrombotics (r(s) = 0.211; P = 0.029). The median scores
      in patients requiring the blood transfusion were 10 in the entire group and 11 in
      users of aspirin or antithrombotics, compared with 3 and 4, respectively, in
      those not transfused (P < 0.001). CONCLUSIONS: The Blatchford scores are
      significantly elevated in users of non-steroidal anti-inflammatory drugs, low
      dose aspirin, and other antithrombotic drugs. They correlate positively with the
      duration of admission and the need for blood transfusion.

PMID- 16907896
TI  - Impact of Helicobacter pylori on the management of dyspepsia in primary care.
AB  - BACKGROUND: It is unclear what impact Helicobacter pylori infection has had on
      the management of dyspepsia in primary care and to what extent published
      guidelines on H. pylori are implemented in routine clinical practice. AIM: To
      assess the impact of H. pylori infection on the management of dyspepsia in
      primary care. METHODS: Patients referred by primary care doctors to an open
      access 13-carbon urea breath test service over a 2-year period for their first
      urea breath test were included in the study. Individual breath results were
      linked with data on prescribing obtained from the General Medical Services
      prescription database. RESULTS: Of 805 patients, 374 (47%) had a positive urea
      breath test and 431 (54%) a negative urea breath test. Of positive urea breath
      test patients, only 245 (64%) were prescribed eradication therapy in the 3 months
      after the breath test and only 43% were referred back for re-testing. In the year
      after the urea breath test, there was a significant fall in prescribing of
      antisecretory therapy which was greatest in the patients who received H. pylori
      therapy (P < 0.001). CONCLUSIONS: There appears to be under and inappropriate
      treatment of H. pylori infection in primary care, and a low rate of re-testing
      after eradication, indicating that current guidelines are not well implemented in
      practice.

PMID- 16907897
TI  - The 13carbon urea breath test for the diagnosis of Helicobacter pylori infection
      in subjects with atrophic gastritis: evaluation in a primary care setting.
AB  - BACKGROUND: (13)Carbon urea breath testing is reliable to detect current
      infection with Helicobacter pylori but has been reported to be of limited value
      in selected patients with atrophic body gastritis or acid-lowering medication.
      AIM: To evaluate the accuracy of (13)carbon urea breath testing for H. pylori
      detection in 20 asymptomatic patients with histologically confirmed atrophic body
      gastritis in a primary care setting. METHODS: (13)Carbon urea breath testing and
      serology were compared with H. pylori culture of a corpus biopsy as reference
      test. RESULTS: All tests were in agreement in 12 patients, being all positive in
      six and all negative in six. One patient was positive for serology and culture
      but negative for (13)carbon urea breath testing, five patients had only positive
      serology and two patients had only positive (13)carbon urea breath testing.
      (13)Carbon urea breath testing showed an accuracy with culture of 85% and anti-H.
      pylori serology with culture of 75%. (13)Carbon urea breath testing carried out
      in patients with positive serology showed an accuracy of 92%. Receiver operating
      characteristic curve analysis of (13)carbon urea breath testing shows optimal
      discrimination at the prescribed cut-off value. CONCLUSIONS: (13)Carbon urea
      breath testing can be used as diagnostic H. pylori test in asymptomatic patients
      with atrophic body gastritis, preferably in addition to serology, to select
      subjects for anti-H. pylori therapy.

PMID- 16907899
TI  - Influence of intrapyloric botulinum toxin injection on gastric emptying and meal
      related symptoms in gastroparesis patients.
AB  - BACKGROUND: Recent observations in limited numbers of patients suggest a
      potential benefit of intrapyloric injection of botulinum toxin in the treatment
      of gastroparesis. AIM: To characterize the effect of botulinum toxin on solid and
      liquid gastric emptying and on meal-related symptoms. METHODS: In 20
      gastroparesis patients (17 women, mean age 37 +/- 3 years, three diabetic and 17
      idiopathic), gastric emptying for solids and liquids was measured before and one
      month after intrapyloric botulinum toxin 4 x 25 units. Before the meal and at 15
      min intervals up to 240 min postprandially, the patient graded the intensity of
      six gastroparesis symptoms, and a meal-related severity score was obtained by
      adding all intensities. Data (mean +/- S.E.M.) were compared using paired
      Student's t-test. RESULTS: Treatment with botulinum toxin significantly enhanced
      solid (t(1/2) 132 +/- 16 vs. 204 +/- 35 min, P < 0.05) but not liquid (92 +/- 10
      vs. 104 +/- 11 min, N.S.) emptying. This was accompanied by a significant
      decrease in cumulative meal-related symptom score (73.5 +/- 16.3 vs. 103 +/- 17.1
      baseline, P = 0.01) as well as individual severity scores for postprandial
      fullness, bloating, nausea and belching (all P < 0.001, two-way anova).
      CONCLUSIONS: Botulinum toxin improves solid but not liquid gastric emptying in
      gastroparesis, and this is accompanied by significant improvement of several meal
      related symptoms.

PMID- 16907898
TI  - Impaired neutrophil chemotaxis in Crohn's disease relates to reduced production
      of chemokines and can be augmented by granulocyte-colony stimulating factor.
AB  - BACKGROUND: Defective neutrophil recruitment has been described as a primary
      pathogenic abnormality in Crohn's disease. Cantharidin-induced blisters provide a
      novel investigative tool to assess cellular influx and inflammatory mediator
      production during acute inflammation and allows the effects of therapy on these
      parameters to be measured. AIMS: To determine whether reduced neutrophil tissue
      penetration in Crohn's disease relates to impaired production of inflammatory
      mediators, and whether it can be reversed by granulocyte-colony stimulating
      factor (G-CSF). METHODS: Neutrophil and monocyte/macrophage populations and
      inflammatory mediators were measured in cantharidin blisters at 24 h. Neutrophil
      chemotaxis was assessed in vitro using blister fluid as the chemoattractant. The
      effect of s.c. G-CSF on blister phenotype was determined. RESULTS: Significantly
      fewer neutrophils migrated into blisters in Crohn's patients. The production of
      neutrophil chemokines, but not other inflammatory mediators, was reduced. This
      significantly correlated with reduced chemotaxis in vitro. Differences were
      unrelated to caspase-recruitment domain 15 genotype. G-CSF significantly
      increased blister neutrophil concentrations in control subjects and Crohn's
      patients. CONCLUSIONS: Reduced neutrophil migration during acute inflammation in
      Crohn's disease is associated with impaired production of appropriate
      chemoattractants. G-CSF therapy increases neutrophil tissue migration, which may
      partially account for its observed therapeutic effect.

PMID- 16907900
TI  - Effect of repeated capsaicin ingestion on intestinal chemosensation and
      mechanosensation.
AB  - BACKGROUND: Ingestion of capsaicin reduces symptoms in functional dyspepsia but
      induces upper abdominal symptoms initially. AIMS: To evaluate the effects of one
      week of oral dosing with capsaicin on mechanonociception and chemonociception.
      METHODS: Healthy subjects ingested capsules containing 0.5 mg capsaicin t.d.s (n
      = 8) or placebo (n = 5) for 7 days. Before (day 0) and after (day 8) capsule
      ingestion the jejunum was distended with a balloon and perfused with a capsaicin
      solution. A graded questionnaire evaluated distension- and capsaicin-induced
      sensation, aggregate perception scores were calculated. RESULTS: Infusion of
      capsaicin induced sensations similar to distension. In subjects receiving
      capsaicin capsules, mean +/- S.E.M. perception scores at 24 mL distension volumes
      were 4.7 +/- 1.2 (day 0) and 3.2 +/- 1.3 (day 8, N.S.). Distension with 40 mL
      induced perception scores of 10.3 +/- 1.0 vs. 8.2 +/- 1.0 (P < 0.05). During
      capsaicin perfusion, first sensation was reported after 13.2 +/- 1.9 min (day 0)
      and 8.1 +/- 0.8 min (day 8, N.S.), discomfort thresholds after 44.1 +/- 6.0 and
      31.2 +/- 5.7 min (P < 0.05). In the placebo group, mechano- and chemonociception
      remained unaltered on days 0 and 8. CONCLUSIONS: One week of ingestion of
      capsaicin sensitized chemonociceptors, while sensitivity of mechanonociceptors
      for distension decreased. Painful sensations during the first week of treatment
      with capsaicin can be attributed to a sensitizing effect of capsaicin on
      vanilloid receptors.

PMID- 16907901
TI  - Evaluation of topical pharyngeal anaesthesia by benzocaine lozenge for upper
      endoscopy.
AB  - BACKGROUND: Among the randomized controlled trials evaluating the effect of
      pharyngeal anaesthesia only some suggest benefit. Spray is irritating for some
      people and leaves bitter taste in the throat. We hypothesized that delivering the
      local anaesthetic as a sucking lozenge would benefit the patients in terms of
      decreasing anxiety and will improve procedure performance and patient tolerance.
      AIM: To determine whether benzocaine/tyrothricin sucking lozenges with conscious
      sedation is superior to conscious sedation alone, with respect to procedure
      performance and tolerance in patients undergoing upper endoscopy. METHODS: One
      hundred and seventy-four adult patients undergoing upper endoscopy with conscious
      sedation completed the study. They were randomized to receive sucking lozenge
      containing benzocaine or placebo before the procedure. Patients were asked to
      rate prestudy anxiety, tolerance for topical pharyngeal anaesthesia, comfort
      during endoscopy, degree of difficulty of intubation, postprocedure throat
      discomfort and willingness to undergo subsequent examinations using a 10-cm
      visual analogue scale. Endoscopists were asked to estimate the ease of
      oesophageal intubation and procedure performance. RESULTS: No significant
      statistical differences regarding all the points studied were found between the
      groups. CONCLUSIONS: Topical pharyngeal anaesthesia with benzocaine/tyrothricin
      lozenges with conscious sedation has no advantages over conscious sedation alone
      in patients undergoing upper endoscopy.

PMID- 16907902
TI  - Re-infection following successful eradication of Helicobacter pylori infection.

PMID- 16907904
TI  - Statins for non-alcoholic fatty liver disease: a new indication?

PMID- 16907905
TI  - The emergence of Beijing family genotypes of Mycobacterium tuberculosis and low
      level protection by bacille Calmette-Guerin (BCG) vaccines: is there a link?
AB  - The world is confronted with major tuberculosis (TB) outbreaks at a time when the
      protection of bacillus Calmette-Guerin (BCG) vaccine has become inconsistent and
      controversial. Major TB outbreaks are caused by a group of genetically similar
      strains of Mycobacterium tuberculosis (Mtb) strains, including the Beijing family
      genotypes. The Beijing family genotypes exhibit important pathogenic features
      such high virulence, multi-drug resistance and exogenous reinfection. These
      family strains have developed mechanisms that modulate/suppress immune responses
      by the host, such as inhibition of apoptosis of infected macrophages, diminished
      production of interleukin (IL)-2, interferon (IFN)-gamma, tumour necrosis factor
      (TNF)-alpha and elevated levels of IL-10 and IL-18. They demonstrate distinct
      expression of proteins, such as several species of alpha-crystallin (a known Mtb
      virulence factor), but decreased expression of some antigens such as heat shock
      protein of 65 kDa, phosphate transport subunit S and a 47-kDa protein. In
      addition, the Beijing family strains specifically produce a highly bioactive
      lipid (a polyketide synthase)-derived phenolic glycolipid. This altered
      expression of proteins/glycolipids may be important factors underlying the
      success of the Beijing family strains. The Beijing family strains are speculated
      to have originated from South-east Asia, where BCG vaccination has been used for
      more than 60 years. The hypothesis that mass BCG vaccination may have been a
      selective factor that favoured genotypic and phenotypic characteristic acquired
      by the Beijing family strains is discussed.

PMID- 16907906
TI  - Presence of plasma complement regulatory proteins clusterin (Apo J) and
      vitronectin (S40) on circulating immune complexes (CIC).
AB  - The complement regulatory (CR) proteins clusterin and vitronectin bind to the
      membrane attack complex (MAC) and thus prevent cytolysis. In this report, we
      demonstrate the presence of both of these CR proteins on MAC bound to circulating
      immune complexes (CIC). We measured the amount of clusterin and vitronectin on
      MAC in plasma, also referred to as soluble MAC (SMAC), as well as on MAC bound to
      CIC (MAC-CIC), using antibody directed to polymerized C9 in systemic lupus
      erythematosus (SLE) patients. We observed a strong correlation among the
      quantities of SMAC and MAC-CIC. The amount of both clusterin and vitronectin
      associated with MAC-CIC was two- to threefold higher in comparison to the SMAC.
      Patients with high levels of clusterin and vitronectin demonstrated renal
      involvement. We hypothesize that these complement regulatory proteins besides
      regulating the insertion of MAC play other critical roles, in disease
      pathogenesis.

PMID- 16907907
TI  - Evidence for extrathymic T cell maturation after thymectomy in infancy.
AB  - Our previous study showed that children who had been partially or completely
      thymectomized during heart surgery as infants had lower proportions and numbers
      of total lymphocytes and reduced proportions of T cells (CD3(+)), helper T cells
      (CD4(+)) and naive T cells (CD3(+) CD4(+) CD45RA(+)), but normal proportion of
      cytotoxic T cells (CD8(+)). In this study T lymphocytes from a selected group of
      eight of these children and age- and gender-matched controls were characterized
      further using flow cytometry to determine phenotypes of T cells and T cell
      subsets related to T cell regulation and phenotypes suggestive of extrathymic
      maturation. Immune function was assessed by measuring autoantibodies and
      antibodies against vaccines. The study group had significantly lower numbers of
      all the main subsets of T lymphocytes and the composition was different. Thus,
      the proportions of lymphocytes with the following phenotypes: CD3(+), CD2(+),
      CD7(+), CD4(+), CD62L(+), CD4(+) CD62L(+) and CD4(+) CD69(-) were significantly
      reduced in the study group compared with the control group, but significantly
      higher proportions were seen of lymphocytes expressing CD8alpha(+) CD8beta(-) and
      TCRgammadelta(+) CD8alpha(+) CD8beta(-). The absolute number and proportion of
      CD4(+) CD25(+) cells were reduced but the proportions of the subgroup of naive
      regulatory T cells (CD4(+) CD25(+) CD62L(+)) and non-activated regulatory T cells
      (CD4(+) CD25(+) CD69(-)) were not reduced in the thymectomized children. We
      conclude that the phenotypic characteristics of T lymphocytes of children who
      have lost their thymus in infancy are indicative of extrathymic maturation. T
      regulatory cells appear to be less affected than other subsets by the general
      reduction in T cell numbers.

PMID- 16907908
TI  - Compartmentalization of intracellular proinflammatory cytokines in bronchial
      intraepithelial T cells of stable lung transplant patients.
AB  - Allograft rejection remains a major cause of morbidity and mortality following
      lung transplantation and is associated with an increased expression of T cell
      proinflammatory cytokines. We have shown that CD4(+) T cell proinflammatory
      cytokine production was significantly reduced in peripheral blood and
      bronchoalveolar lavage (BAL) of stable lung transplant patients, consistent with
      immunosuppression therapy. However, analysis of inflammatory cytokine profiles of
      intraepithelial T cells in bronchial brushing (BB) may be more relevant than
      peripheral blood or BAL T cells for assessing immune graft status. To investigate
      the immunomodulatory effects of currently used immunosuppressive regimens on
      bronchial intraepithelial T cell cytokine production, whole blood, BAL and BB
      from stable lung transplant patients and control volunteers were stimulated in
      vitro and cytokine production by CD8(+) and CD4(+) T cell subsets determined
      using multi-parameter flow cytometry. In bronchial intraepithelial T cell subsets
      in control subjects and transplant patients there was compartmentalization of
      interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha production, a
      decrease in interleukin (IL)-2 production by CD4(+) T cells and CD4 : CD8
      inversion compared with blood and BAL. Although there was a decrease in T cell
      proinflammatory cytokine production in blood of transplant patients, this was not
      found in BAL or bronchial intraepithelial CD8 T cell subsets, suggesting that the
      same level of immunosuppression may not occur in the lung of transplant
      recipients. Drugs that effectively reduce CD8 T cell proinflammatory cytokine
      production in the lung compartment may improve current protocols for reducing
      graft rejection in these patients.

PMID- 16907909
TI  - Defective maturation of dendritic cells in common variable immunodeficiency.
AB  - Monocyte-derived dendritic cells (MdDCs) from many patients with common variable
      immunodeficiency (CVID) have been shown recently to have reduced expression of
      surface molecules associated with maturity. Using flow cytometry and confocal
      microscopy, we now show that this is due to a partial failure to fix Class II DR
      molecules on the surface during procedures that induce full maturation in vitro
      in cells from normal subjects. Major histocompatibility complex (MHC) class I,
      CD86 and CD83 expression were expressed normally, but CD40 was reduced. These
      abnormalities are unlikely to be due to prior in vivo exposure of monocytes to
      lipopolysaccharide (LPS), as addition of LPS to monocytes from normal subjects in
      vitro caused a different pattern of changes. CVID MdDCs retained Class II DR in
      the cytoplasm during maturation, showed increased internalization of cross-linked
      Class II DR surface molecules and were unable to polarize DR within a lipid raft
      at contact sites with autologous lymphocytes. These cells retained some features
      of monocytes, such as the ability to phagocytose large numbers of fixed yeast and
      fluorescent carboxylated microspheres and expression of surface CD14. These
      abnormalities, if reflected in vivo, could compromise antigen presentation and
      may be a fundamental defect in the mechanism of the antibody deficiency in a
      substantial subset of CVID patients.

PMID- 16907910
TI  - Different inflammatory cell pattern and macrophage phenotype in chronic
      obstructive pulmonary disease patients, smokers and non-smokers.
AB  - Smokers exhibit airway inflammation and increased number of alveolar macrophages
      (AM), but not all develop chronic obstructive pulmonary disease (COPD). We
      hypothesized that AMs in COPD patients have an altered functional capacity
      mirrored in a different phenotype. Sixteen steroid-naive COPD patients [forced
      expiratory volume in 1 s (FEV(1)) < 70% of predicted] underwent bronchoalveolar
      lavage (BAL). Age- and smoking-matched non-obstructive smokers (n = 10) and
      healthy non-smokers (n = 9) served as controls. Nine COPD patients had a BAL cell
      yield sufficient for flow cytometry analysis, where expression of AM cell surface
      markers reflecting various functions was determined. AMs from COPD patients
      showed decreased expression of CD86 (co-stimulation) and CD11a (adhesion)
      compared to smokers' AMs (P < 0.05). Furthermore, smokers' AMs showed lower (P <
      0.05) expression of CD11a compared to non-smokers. AM expression of CD11c was
      higher in the COPD and smokers groups compared to non-smokers (P < 0.05). The
      expression of CD54 (adhesion) was lower in smokers' AMs compared to non-smokers
      (P < 0.05), whereas CD16 was lower (P < 0.05) in COPD patients compared to non
      smokers. The AM expression of CD11b, CD14, CD58, CD71, CD80 and human leucocyte
      antigen (HLA) Class II did not differ between the three groups. The AM phenotype
      is altered in COPD and further research may develop disease markers. The lower AM
      expression of CD86 and CD11a in COPD implies a reduced antigen-presenting
      function. Some alterations were found in smokers compared to non-smokers, thus
      indicating that changes in AM phenotype may be associated with smoking per se.
      The functional relevance of our findings remains to be elucidated.

PMID- 16907911
TI  - A reproducible method for the enumeration of functional (cytokine producing)
      versus non-functional peptide-specific cytotoxic T lymphocytes in human
      peripheral blood.
AB  - One of the most difficult laboratory challenges in the field of therapeutic
      cancer vaccines has been the development of uncomplicated/reproducible methods
      for the quantification of vaccine immunization efficacy in peripheral blood of
      cancer patients. Existing methods are limited by lack of functional information
      (tetramers), difficulties with standardization/reproducibility [enzyme-linked
      immunosorbent spot (ELISPOT)] and reliance on endogenous (sample-specific)
      antigen presentation (cytokine flow cytometry). Herein we present a reproducible
      method utilizing an artificial antigen-presenting cell platform for flow
      cytometry-based quantification of the frequency and activation status of peptide
      specific cytotoxic T lymphocytes. The methodology [currently presented for
      cytomegalovirus human leucocyte antigen (HLA)-A2 cognant peptide antigens] allows
      simultaneous ex vivo quantification of activated (cytokine-producing) and
      inactive tetramer-positive T cells following HLA class I/peptide/CD28 stimulation
      independent of endogenous antigen presentation. The simplicity and reliability of
      the assay provide for high-throughput applications and automation. The utility
      and application of this method are discussed.

PMID- 16907912
TI  - Triggering receptor expressed on myeloid cells (TREM-1) is regulated post
      transcriptionally and its ligand is present in the sera of some septic patients.
AB  - Inflammation is necessary for survival, but it is also an important cause of
      human morbidity and mortality, as exemplified by sepsis. During inflammation,
      cells of the innate immune system are recruited and activated in response to
      infection, trauma or injury. These cells are activated through receptors, such as
      Toll-like receptors (TLRs), which recognize microbial ligands such as
      lipopolysaccharide (LPS). Triggering receptor expressed on myeloid cells (TREM)-1
      amplifies the inflammatory response initiated by TLRs, and its expression on the
      surface of monocytes increases in the presence of TLR ligands. Here we have shown
      that in monocytes TREM-1 mRNA levels, measured by reverse transcription
      polymerase chain reaction (RT-PCR), remained unchanged and TREM-1 protein levels,
      measured by flow cytometry, increased, indicating that LPS increases TREM-1
      expression by a post-transcriptional mechanism. We also showed that TREM-1/Fc
      fusion protein decreased the ability of the sera of some patients with sepsis to
      activate monocytes, indicating that the TREM-1 ligand, whose identity is unknown,
      may be present in the sera of some of these patients. We describe a mechanism for
      the regulation of TREM-1 expression on monocytes and the possible presence of its
      ligand in serum; these findings help to explain the contribution of TREM-1 during
      systemic inflammation.

PMID- 16907913
TI  - Expression and function of Toll-like receptor 9 in severely injured patients
      prone to sepsis.
AB  - The purpose of this prospective study was to enumerate Toll-like receptor 9
      (TLR9)(+) cells and measure their function using synthetic oligonucleotides
      enriched in CG dinucleotide motifs (CpG)-induced proliferation within 48 h after
      trauma in severely injured patients prone to sepsis. Sixteen consecutive trauma
      patients with an injury severity score (ISS) > 21 and 16 blood donors (controls)
      were included in this study. Using two-colour flow cytometry, TLR9 expression was
      detectable intracellularly and also on the surface of B lymphocytes. The surface
      expression of TLR9 of B lymphocytes from whole blood and peripheral blood
      mononuclear cells (PBMC) stimulated with CpG was significantly increased in B
      cells of severely injured patients prone to sepsis compared to controls. No
      significant differences could be observed between CpG-induced proliferation of
      PBMC of severely injured patients prone to sepsis and controls. As a measure of
      immunosuppression, human leucocyte antigen (HLA)-DR expression of monocytes of
      the trauma patients was significantly diminished compared with controls in PBMC
      and in whole blood. Immunosuppression in the early phase after trauma seems not
      to be associated with a disturbed sensing of bacterial DNA.

PMID- 16907914
TI  - Mannan-binding lectin plasma levels in leprosy: deficiency confers protection
      against the lepromatous but not the tuberculoid forms.
AB  - Mannan-binding lectin (MBL) is an important component of the first-line defence
      against infections. Evidence has shown that MBL deficiency, reducing phagocytosis
      and internalization of intracellular pathogens may protect the host against
      intracellular infections such as leprosy. In this study, we speculated whether
      genetically determined low MBL serum levels confer protection against
      Mycobacterium leprae infection. One hundred and ninety-one patients with leprosy,
      presenting lepromatous (n = 118), tuberculoid (n = 31), dimorph (n = 30) and
      indeterminate (n = 12) clinical forms and 110 healthy controls matched with the
      patients according to sex, age and ethnic background were investigated. MBL
      concentrations were measured in a double-antibody enzyme immune assay and C
      reactive protein (CRP) serum levels by nephelometry. A significant negative
      association of MBL low values (< 100 ng/ml) was observed with lepromatous
      patients when comparing with controls and tuberculoid patients [10/118,
      8.47%versus 21/110, 19.09%P = 0.03 chi(2) with Yates' correction, odds ratio (OR)
      0.39, confidence interval (CI) 0.18-0.88 and 8/31, 25.81%, P = 0.02, OR 0.27, CI
      0.09-0.75, respectively]. There was no significant difference in the distribution
      of MBL levels between patients and controls or among the clinical forms. The
      concentration of CRP was significantly increased in the patients (P = 0.0002) and
      in the lepromatous form (P = 0.0001) when compared to controls. A weak positive
      correlation between MBL and CRP levels was observed in the patients (P = 0.010, R
      = 0.255). These data suggest a protective role for MBL deficiency against the
      development of the most severe and multi-bacillary form of leprosy.

PMID- 16907915
TI  - The activity of the immunoregulatory enzyme indoleamine 2,3-dioxygenase is
      decreased in smokers.
AB  - Indoleamine 2,3-dioxygenase (IDO), an enzyme involved in the degradation of the
      essential amino acid tryptophan (trp) to its main metabolite kynurenine (kyn),
      suppresses T cell activity. Smoking has marked immunomodulatory effects, above
      all immunosuppressive, causing a reduction in the levels of immunoglobulins and
      an increased risk of infections. The immunostimulatory effects of smoking are
      manifested, for example, in increased autoantibody production. We sought to
      establish whether IDO activity is involved in the immunomodulatory effects of
      smoking. To this end we measured the ratio of kyn to trp, reflecting IDO
      activity, by reverse-phase high-performance liquid chromatography (HPLC) in 784
      (464 female, 230 male) subjects of a population-based sample of the adult Finnish
      population. Serum cotinine concentration as an indicator of active smoking was
      measured in the patients by radioimmunoassay and detailed data gathered on
      smoking habits. IDO activity was lower in smokers in this population-based sample
      compared with non-smokers when active smoking was classified according to serum
      cotinine concentration or history of smoking habits. Moreover, serum IDO activity
      correlated inversely with serum cotinine concentration. In conclusion, the
      activity of the IDO enzyme is decreased in smoking subjects, and the reduction in
      IDO-dependent immunosuppression could thus be responsible for the known
      immunostimulatory effects of smoking.

PMID- 16907916
TI  - Intracellular cytokine profile of T lymphocytes in patients with chronic
      obstructive pulmonary disease.
AB  - Chronic obstructive pulmonary disease (COPD) is characterized by an excessive
      inflammatory response to inhaled particles, mainly tobacco smoking. T lymphocytes
      are important regulatory cells that secrete several cytokines and participate
      actively in this inflammatory response. According to the pattern of cytokines
      secreted, the immune response is classified as cytotoxic or type 1 [interferon
      (IFN)-gamma-, interleukin (IL)-2-dependent] and humoral or type 2 (IL-4-, IL-5-,
      IL-10- and IL-13-dependent). This paper sought to compare the intracellular
      profile of cytokine expression determined by flow cytometry in T lymphocytes
      harvested from bronchoalveolar lavage (BAL) and peripheral blood in patients with
      COPD, smokers with normal lung function and never smokers. We found that BAL T
      lymphocytes from COPD patients had a higher percentage of positive stained cells
      for most of the cytokines analysed when compared to never smokers or smokers with
      normal lung function. Differences reached statistical significance for IL-4, IL
      10 and IL-13, particularly in CD8(+) T cells. Furthermore, the expression of most
      of these cytokines was related inversely to the degree of airflow obstruction
      present suggesting local activation and/or selective homing of T lymphocytes to
      the lungs in COPD patients. These observations were not reproduced in circulating
      T lymphocytes. These results suggest that BAL T lymphocytes in patients with COPD
      produce more cytokines than in controls and tend to show a type 2 pattern of
      intracellular cytokine expression, particularly a Tc-2 profile. This is related
      inversely to the degree of airflow obstruction present.

PMID- 16907917
TI  - Association of interferon-gamma and interleukin 10 genotypes and serum levels
      with partial clinical remission in type 1 diabetes.
AB  - We studied whether serum interferon (IFN)-gamma or interleukin (IL)-10 levels and
      their corresponding functional polymorphic genotypes are associated with partial
      remission of type 1 diabetes (T1D). A multi-centre study was undertaken in
      patients with newly diagnosed T1D and matched controls. T1D patients were
      followed for 3 months and characterized for remission status. Partial clinical
      remission was defined as a daily insulin dose <or= 0.38 units/kg/24 h with an
      HbA1c <or= 7.5%. Thirty-three patients and 32 controls were phenotyped for serum
      concentrations of IFN-gamma and IL-10 and genotyped for functional polymorphisms
      of the IFN-gamma and IL-10 genes. Sixteen of 25 informative patients (63%)
      remitted. Serum IFN-gamma concentrations were significantly decreased in
      remitters but increased in non-remitters compared to controls, and did not change
      over time in any group. IFN-gamma genotypes corresponded with serum levels in
      controls and non-remitters, but not in remitters who displayed the lowest serum
      IFN-gamma levels despite more often carrying high-producing IFN-gamma genotypes.
      Neither the frequency of IL-10 genotypes nor serum IL-10 concentration differed
      between patients and controls. The combination of high-producing IFN-gamma
      genotype together with low serum IFN-gamma concentration at the time of diagnosis
      provided a strong positive predictive value for remission. Serum IFN-gamma
      concentrations predicted by genotype and observed serum levels were discordant in
      remitters, suggestive of regulation overruling genetic predisposition. Although
      high-producing genotypes were less frequent in remitters, they were predictive of
      remission in combination with low serum IFN-gamma levels. These data imply that
      remission is partially immune-mediated and involves regulation of IFN-gamma
      transcription.

PMID- 16907918
TI  - (-)-Epigallocatechin-3-gallate protects mice from concanavalin A-induced
      hepatitis through suppressing immune-mediated liver injury.
AB  - (-)-Epigallocatechin-3-gallate (EGCG) is the major active component of green tea.
      Increasing evidence has suggested that EGCG exhibits anti-inflammatory, anti
      oxidant and immunosuppressive effects. In this study, we investigated the effect
      of EGCG on concanavalin A (ConA)-induced hepatitis (CIH) in mice, a model of
      immune-mediated liver injury in humans. We pretreated mice with EGCG before ConA
      injection, and then measured alanine aminotransferase (ALT) levels in plasma,
      inflammatory infiltration and hepatocyte apoptosis in liver. Potential
      therapeutic mechanisms were elucidated further by measuring several inflammatory
      mediators. Mice pretreated with EGCG exhibited much less increased ALT levels in
      plasma, reduced inflammatory infiltration and hepatocyte apoptosis in liver
      compared with control mice pretreated with vehicle solutions. We further
      investigated the mechanisms of the protective effects of EGCG. In EGCG-pretreated
      mice, we found abrogated tumour necrosis factor (TNF)-alpha and interferon (IFN)
      gamma at both protein levels in plasma and mRNA levels in liver. At the same
      time, the concentration of nitrite in plasma and inducible nitric oxide synthase
      production in liver were both down-regulated in these mice. Moreover, IFN
      inducible protein-10 and macrophage inflammatory protein-1alpha expressions in
      liver were decreased significantly. Therefore, EGCG is capable of regulating
      immune-mediated liver injury in vivo. The protective effect depended on its
      suppressive effect on the production of important inflammatory mediators.

PMID- 16907919
TI  - Ablation of ovomucoid-induced allergic response by desensitization with
      recombinant ovomucoid third domain in a murine model.
AB  - Attempts to modulate the allergenic response by hypoallergens aimed at
      eliminating IgE-binding epitopes have been established recently for allergen
      immunotherapy. Desensitization offers an alternative approach to mounting a
      protective immune response. We have shown previously that mutation of the
      decisive amino acids in the B cell epitope of the ovomucoid third domain
      suppresses IgE binding reactivity against human patient sera and we hypothesize
      that this hypoallergenic variant could be a potential candidate molecule for
      specific immunotherapy against an ovomucoid-induced IgE reaction. The aim of this
      study was to investigate whether hyposensitization with the ovomucoid-modified
      isoform could desensitize ovomucoid-sensitized mice. We mapped the immunodominant
      B cell epitopes of ovomucoid in Balb/c mice. A hypoallergenic ovomucoid mutant
      isoform, having ablated allergenicity against patient sera, was used to
      desensitize ovomucoid-sensitized Balb/c mice by intraperitoneal injection. Female
      Balb/c mice were sensitized with intact ovomucoid molecule (Fovm) and
      desensitized with the modified isoform of the third domain of ovomucoid (GMFA).
      Intact ovomucoid-sensitized mice desensitized with phosphate-buffered saline
      (PBS) served as positive controls to maintain hypersensitivity. To gain insight
      into the efficacy of the modified ovomucoid variant in desensitization, effects
      on hypersensitivity reactions and histamine levels, followed by its association
      with antibody levels and cytokine profiles, were measured. Abrogation of the
      allergic response with complete suppression of anaphylactic symptoms and lower
      serum histamine levels was observed in the desensitized group by GMFA,
      accompanied by significantly reduced ovomucoid-specific IgE and IgG1 levels and
      enhanced specific IgG and IgG2a levels. The sensitized group showed severe
      anaphylactic symptoms, enhanced serum histamine concentrations and increased
      levels of specific IgE and IgG1. The level of interleukin (IL)-4 was decreased
      dramatically in the desensitized group and higher levels of interferon (IFN)
      gamma were found, whereas mice sensitized with intact ovomucoid exhibited
      significantly higher levels of IL-4 favouring a Th2 skewed pathway. We
      demonstrate clearly that GMFA is able to ablate ovomucoid-induced allergic
      reactions in sensitized mice. This occurs via a suppression of specific IgE
      accompanied by an increase in suppressor T cell activity. This approach offers
      some promise for the development of treatment against ovomucoid-induced allergic
      response.

PMID- 16907920
TI  - In the rat, citrullinated autologous fibrinogen is immunogenic but the induced
      autoimmune response is not arthritogenic.
AB  - Conversion of arginyl to citrullyl residues (citrullination) is essential for the
      formation of the epitopes recognized by rheumatoid arthritis (RA)-associated
      autoantibodies to citrullinated proteins (ACPA). ACPA are secreted by plasma
      cells of the rheumatoid synovial tissue where their major target, citrullinated
      fibrin, is abundant. Although numerous arguments suggest that ACPA play an
      important role in RA, their pathological relevance remains to be established. In
      the present study, we assessed the immunogenicity and arthritogenicity of
      complete Freund's adjuvant-emulsified autologous citrullinated (C-rFBG) or non
      citrullinated (NC-rFBG) fibrinogen in Lewis (LEW) and Brown-Norway rats, which
      exhibit drastic differences in their susceptibility to induced autoimmune
      diseases. NC-rFBG induced no antibody response. In contrast, a single injection
      of C-rFBG induced an IgG response directed mainly to citrullinated determinants
      of rFBG. However, all rat strains remained devoid of clinical and histological
      signs of arthritis up to 3 months after C-rFBG inoculation. Next, in LEW rats, we
      tested whether autoimmunity to C-rFBG could aggravate acute ankle arthritis
      triggered by intra-articular injection of incomplete Freund's adjuvant (IFA).
      However, such arthritis evolved identically in the presence or absence of anti-C
      rFBG autoantibodies. However, IFA-injected joints were devoid of citrullinated
      fibrin deposits. Therefore, citrullination allows breakdown of immunological
      tolerance but the autoimmune response developed is not spontaneously
      arthritogenic. Whether or not it can aggravate arthritis with citrullinated
      fibrin deposits remains to be evaluated.

PMID- 16907921
TI  - The role of CD4CD25 T cells in autoantibody production in murine lupus.
AB  - Systemic lupus erythematosus (SLE) is a chronic, systemic autoimmune disease
      characterized by the loss of tolerance to self-antigen. Because it is currently
      not known if regulatory T (T(reg)) cells are involved in the pathogenesis, we
      determined the frequency of CD4(+)CD25(+) T cells and assayed the related gene
      expression levels in CD4(+)CD25(+) T cells isolated from both lupus mice (NZB/NZW
      F(1)) and normal control mice (DBA2/NZW F(1)). The results showed that the
      frequency of CD4(+)CD25(+) T cells in lupus mice was lower than that of normal
      mice. Except for the high expression level of interleukin (IL)-10 mRNA,
      CD4(+)CD25(+) T cells from lupus mice expressed normal forkhead box P3 (Foxp3)
      and transforming growth factor (TGF)-beta mRNA, and exerted suppressive
      functions. Furthermore, we depleted CD25(+) T(reg) cells of non-autoimmune mice
      with anti-CD25 antibody and broke their tolerance with apoptotic cell-pulsed
      dendritic cells for the follow-up of autoantibody levels. The mice in the CD25(+)
      cell-depleted group had higher titres of anti-double-strand/single-strand DNA
      antibodies than those of the isotype control antibody-treated group. These
      findings indicated that CD4(+)CD25(+) T cells might be involved in the regulatory
      mechanism of autoantibody production.

PMID- 16907922
TI  - Assessment of in vitro immunity to Mycobacterium tuberculosis in a human
      peripheral blood infection model using a luciferase reporter construct of M.
      tuberculosis H37Rv.
AB  - Protective immune responses to tuberculosis in man are primarily cell-mediated
      and require the interaction of specific T cells, cytokines and activated
      macrophages. In the present study, Mycobacterium tuberculosis H37Rv labelled with
      luciferase reporter enzyme was used to analyse the anti-mycobacterial immunity in
      man using an in vitro whole blood infection model. Peripheral blood samples
      obtained from M. bovis bacille Calmette-Guerin (BCG)-vaccinated tuberculin
      positive healthy volunteers (n = 23) were cultured with M. tuberculosis H37Rv
      reporter strain. The growth of bacteria in the whole blood cultures was monitored
      after 48 and 96 h of infection. The results showed that the growth of M.
      tuberculosis was significantly inhibited after 96 h (P < 0.029) of culture. Among
      the cytokines studied, interleukin (IL)-10 and IL-12 were not detected at all,
      whereas low levels of interferon (IFN)-gamma after 96 h (0.4 IU/ml) and tumour
      necrosis factor (TNF)-alpha after 48 (135 pg/ml) and 96 h (47 pg/ml) of culture
      were detected in the supernatants of whole blood infected with M. tuberculosis.
      The magnitude of bacterial growth correlated directly with the concentration of
      TNF-alpha detected after 48 h (r = 0.722) and 96 h (r = 0.747) of culture (P <or=
      0.0001 and P <or= 0.0001, respectively). However, the addition of monoclonal
      antibodies specific to TNF-alpha and IFN-gamma to the blood cultures did not
      alter mycobacterial growth indicating the role of other mechanisms/factors in
      restricting the growth of M. tuberculosis in whole blood cultures.

PMID- 16907923
TI  - Ultraviolet-A (UVA-1) radiation suppresses immunoglobulin production of activated
      B lymphocytes in vitro.
AB  - Previous studies have shown that low-dose ultraviolet-A (UVA-1) total body
      irradiations were capable of improving disease activity in patients with systemic
      lupus erythematosus (SLE). We hypothesized that UVA-1-induced suppression of
      immunoglobulin production by activated B cells in the dermal capillaries could be
      (partly) responsible for this effect. Our experiments with donor skin
      demonstrated that approximately 40% of UVA-1 could penetrate through the
      epidermis. Irradiation of peripheral blood mononuclear cells (PBMCs) with 2
      J/cm(2) of UVA-1 resulted in 20% cell death. This toxic effect could be prevented
      totally by preincubation of the cell cultures with catalase. This indicates that
      the generation of hydrogen peroxide plays a role in UVA-1 cytotoxicity. T cells
      and B cells appeared to be less susceptible to UVA-1 cytotoxicity than monocytes.
      With the use of a CD40-CD40L B cell activation method we measured immunoglobulin
      production after various doses of UVA-1 irradiation (0-2 J/cm(2)). The doses of 2
      J/cm(2) caused a significant decrease of IgM, IgG, IgA and IgE production under
      the conditions of interleukin (IL)-10 or IL-4 (IgE) stimulation. Although UVA-1
      can cause apoptosis of B lymphocytes, we show that relatively low doses of UVA-1
      radiation also affect the function of these cells. Both effects may be
      responsible for the observed improvement of disease activity in SLE patients.

PMID- 16907924
TI  - Treatment of monocytes with interleukin (IL)-12 plus IL-18 stimulates survival,
      differentiation and the production of CXC chemokine ligands (CXCL)8, CXCL9 and
      CXCL10.
AB  - During inflammation, interleukin (IL)-12 and IL-18 are produced by macrophages
      and other cell types such as neutrophils (IL-12), keratinocytes and damaged
      endothelial cells (IL-18). To explore the role of IL-12 and IL-18 in inflammatory
      innate immune responses we investigated their impact on human peripheral blood
      monocytes and mature bronchoalveolar lavage (BAL) macrophages. IL-12 and IL-18
      together, but not alone, prevented spontaneous apoptosis of cultured monocytes,
      promoted monocyte clustering and subsequent differentiation into macrophages.
      These morphological changes were accompanied by increased secretion of CXC
      chemokine ligands (CXCL)9, CXCL10 (up to 100-fold, P < 0.001) and CXCL8 (up to 10
      fold, P < 0.001) but not CCL3, CCL4 or CCL5. Mature macrophages (from BALs)
      expressed high basal levels of CXCL8, that were no modified upon stimulation with
      IL-12 and IL-18. In contrast, the basal production of CXCL9 and CXCL10 by BALs
      was increased by 10-fold (P < 0.001) in the presence of either IL-12 or IL-18
      alone and by 50-fold in the presence of both cytokines. In conclusion, our
      results indicate a relevant role for IL-12 and IL-18 in the activation and
      resolution of inflammatory immune responses, by increasing the survival of
      monocytes and by inducing the production of chemokines. In particular, those that
      may regulate angiogenesis and promote the recruitment of monocytes, activated T
      cells (CXCL9 and CXCL10) and granulocytes (CXCL8).

PMID- 16907925
TI  - Arginine-specific gingipains from Porphyromonas gingivalis deprive protective
      functions of secretory leucocyte protease inhibitor in periodontal tissue.
AB  - Chronic periodontitis is correlated with Porphyromonas gingivalis infection. In
      this study, we found that the expression of secretory leucocyte protease
      inhibitor (SLPI), an endogenous inhibitor for neutrophil-derived proteases, was
      reduced in gingival tissues with chronic periodontitis associated with P.
      gingivalis infection. The addition of vesicles of P. gingivalis decreased the
      amount of SLPI in the media of primary human gingival keratinocytes compared to
      untreated cultures. We therefore investigated how arginine-specific gingipains
      (Rgps) affect the functions of SLPI, because Rgps are the major virulence factors
      in the vesicles and cleave a wide range of in-host proteins. We found that Rgps
      digest SLPI in vitro, suppressing the release of SLPI. Rgps proteolysis of SLPI
      disrupted SLPI functions, which normally suppresses neutrophil elastase and
      neutralizes pro-inflammatory effects of bacterial cell wall compounds in cultured
      human gingival fibroblasts. The protease inhibitory action of SLPI was not
      exerted towards Rgps. These results suggest that Rgps reduce the protective
      effects of SLPI on neutrophil proteases and bacterial proinflammatory compounds,
      by which disease in gingival tissue may be accelerated at the sites with P.
      gingivalis infection.

PMID- 16907926
TI  - A potential role for interleukin-18 in inhibition of the development of
      Cryptosporidium parvum.
AB  - Accumulating evidence suggests that intestinal epithelial cells (IECs)
      constitutively express the immunoregulatory cytokine interleukin (IL)-18. IECs
      also serve as the host cell for the intracellular parasitic protozoan
      Cryptosporidium parvum. In the present study, C. parvum infection of a human
      enterocyte cell-line HCT-8 resulted in increased expression of IL-18 mRNA as
      measured by quantitative reverse transcription-polymerase chain reaction (RT
      PCR). IL-18 protein was detected in control uninfected cells and following
      infection there was increased expression as measured by enzyme-linked
      immunosorbent assay (ELISA). Gene expression revealed the presence of the IL-18
      receptor subunits not only in cell-lines but also in freshly isolated IECs,
      suggesting that IL-18-mediated signalling events may contribute to epithelial
      host defence during infection. Recombinant IL-18 inhibited intracellular
      development of the parasite in HCT-8 and HT-29 cells. Increased expression of
      bactericidal antibiotic peptides LL-37 and alpha-defensin 2 by IL-18 in HCT-8 and
      HT-29 cells may represent one mode of action by which this pluripotent cytokine
      aids in limiting the development of intracellular pathogens such as C. parvum in
      the gastrointestinal tract.

PMID- 16907929
TI  - Endotoxemia enhances circulating endothelial cells in humans.

PMID- 16907927
TI  - Increased susceptibility of cord blood B lymphocytes to undergo spontaneous
      apoptosis.
AB  - In this study, we compared the rate of spontaneous apoptosis of B cells from
      umbilical cord blood with adult B cells and assessed the role of Bcl-2, CD5,
      interleukin (IL)-4 and B cell-activating factor in B cell spontaneous apoptosis.
      We found that spontaneous apoptosis of cultured B cells, as assessed by utilizing
      annexin-V binding, was significantly higher in cord blood than in healthy adult
      individuals (77.5; 95 CI, 73.5-81.5 versus 59.2; 95 CI, 54-64, respectively, P <
      0.0001) and further confirmed by 4' 6-diamidino-2-phenylindole, dihydrochloride
      (DAPI) staining. Whereas the expression of B cell-activating factor from the
      tumour necrosis factor family (BAFF) receptor mRNA was similar in B cells from
      adults and cord blood, we detected lower levels of circulating BAFF in the serum
      of cord blood (0.68 +/- 0.13 ng versus 1.83 +/- 0.54 ng, P = 0.01). The latter
      may explain, in part, our observation of lower levels of mean fluorescence
      intensity of Bcl-2 in cord B cells compared with adults (1.6 +/- 0.9 versus 2.85
      +/- 1.3, P = 0.033). CD19(+) CD5(+) B cells from cord blood underwent a lower
      rate of apoptosis in comparison to CD19(+) CD5(-) B cells (25.1 +/- 9.3%versus
      58.5 +/- 12.5%, P < 0.0001). This pattern of sensitivity was comparable in adult
      blood (15 +/- 5.5%versus 22.7 +/- 9.3%, P = 0.01). Nevertheless, the rate of
      apoptosis was higher in CD19(+) CD5(+) from cord blood compared to CD19(+) CD5(+)
      from adults (25.1 +/- 9.3%versus 15 +/- 5.5%, P = 0.0013). The addition of rIL-4
      (10 u/ml) to cultured cells decreased B cell apoptosis in a similar fashion in
      both cord and adults blood. This rescue was strengthened when BAFF (100
      microg/ml) was further added. Thus, alterations in Bcl-2 or serum BAFF level may
      explain the increased rate of cord blood B cell apoptosis.

PMID- 16907930
TI  - Endogenous tissue-type plasminogen activator and cardioembolic brain infarct
      subtype.

PMID- 16907931
TI  - Atorvastatin and quinapril inhibit blood coagulation in patients with coronary
      artery disease following 28 days of therapy.
AB  - BACKGROUND: We evaluated the antithrombotic effects of statins and angiotensin
      converting enzyme inhibitor (ACEI) drugs in patients with coronary artery disease
      (CAD). METHODS AND RESULTS: Blood coagulation at the site of microvascular injury
      was assessed in 26 males with CAD before and after treatment with quinapril (10
      mg day-1; n=13) or atorvastatin (40 mg day-1; n=13) for 4 weeks and an additional
      4 weeks of combined therapy (quinapril+atorvastatin). Rates of prothrombin and
      factor V activation (FVa), fibrinogen (Fbg) cleavage and FVa inactivation showed
      that both quinapril and atorvastatin decreased the rates of: formation of
      thrombin B-chain (by 30.6%, P=0.007; and by 34.3%, P=0.003), formation of
      thrombin-antithrombin complexes (by 30.4%, P=0.0002; and by 40%, P=0.001), FV
      activation (by 19.1%, P=0.03; and by 21.8%, P=0.005) and Fbg depletion (by 29.2%,
      P=0.004; and by 32.7%, P=0.001). Atorvastatin alone accelerated FVa inactivation
      (P=0.005). A further 4 weeks of combined therapy enhanced most anticoagulant
      effects only when atorvastatin was added to quinapril. CONCLUSIONS: In CAD
      patients, atorvastatin and quinapril slowed blood clotting at the site of
      microvascular injury after 28 days of therapy. Addition of atorvastatin to
      quinapril, but not quinapril to the statin, enhanced the anticoagulant effects.
      Our findings might help explain the reduced risk of myocardial infarction or
      stroke in patients treated with statins and/or ACEIs and the lack of clinical
      benefits from ACEI added to prior statin therapy in patients at cardiovascular
      risk.

PMID- 16907932
TI  - Recent advances in diabetology: diabetic dermopathy, autoantibodies in the
      prediction of the development of type 1 diabetes, and islet cell transplantation
      and inhaled insulin as treatment for diabetes.

PMID- 16907933
TI  - Oxidative stress and apoptotic events during thermal stress in the symbiotic sea
      anemone, Anemonia viridis.
AB  - Symbiosis between cnidarian and photosynthetic protists is widely distributed
      over temperate and tropical seas. These symbioses can periodically breakdown, a
      phenomenon known as cnidarian bleaching. This event can be irreversible for some
      associations subjected to acute and/or prolonged environmental disturbances, and
      leads to the death of the animal host. During bleaching, oxidative stress has
      been described previously as acting at molecular level and apoptosis is suggested
      to be one of the mechanisms involved. We focused our study on the role of
      apoptosis in bleaching via oxidative stress in the association between the sea
      anemone Anemonia viridis and the dinoflagellates Symbiodinium species.
      Characterization of caspase-like enzymes were conducted at the biochemical and
      molecular level to confirm the presence of a caspase-dependent apoptotic
      phenomenon in the cnidarian host. We provide evidence of oxidative stress
      followed by induction of caspase-like activity in animal host cells after an
      elevated temperature stress, suggesting the concomitant action of these
      components in bleaching.

PMID- 16907935
TI  - 'A stronger and clearer perception of self'. Women's experience of being
      professional patients in teaching the pelvic examination: a qualitative study.
AB  - OBJECTIVES: To identify and describe the experience of being a professional
      patient (PP) in teaching the pelvic examination (PE). DESIGN: Qualitative study
      using in-depth interviews. SETTING: Participant's home, place of work or other
      place of choice. POPULATION: Thirteen female PPs who teach the PE to medical
      students and student midwives. METHOD: Semi-structured interviews analysed with
      an interpretive phenomenological approach. MAIN OUTCOME MEASURES: Five themes
      were identified during the analysis: 'embodied knowledge', 'promoting a proper
      approach', 'redrawing private boundaries', 'feeling confident' and 'doing
      something meaningful'. The essence 'experience of stronger and clearer perception
      of self' emerged from the themes and is the described structure of the lived
      experience of the women who are PP. CONCLUSIONS: Being a PP in this setting was
      beneficial for the women. They acquired increased knowledge about their bodies
      and PE procedure, which led to a new awareness of their own body. Contributing to
      students' learning in such an intimate examination procedure was rewarding and
      increased self-esteem.

PMID- 16907936
TI  - Referral and attendance at a specialist antenatal clinic: qualitative study of
      women's views.
AB  - OBJECTIVE: To explore women's views on being referred to and attending a
      specialist antenatal hypertension clinic. DESIGN: Qualitative interview study.
      SETTING: A pregnancy hypertension clinic in a large teaching hospital in the East
      Midlands. POPULATION: Twenty-one women (aged 18 years and above) attending the
      pregnancy hypertension clinic for the first time during their current pregnancy.
      METHODS: Women who had been referred to and attended a specialist antenatal
      clinic participated in semi-structured interviews. Data analysis was based on the
      constant comparative method. MAIN OUTCOME MEASURES: Women's experiences and
      perceptions of being referred to and attending a specialist antenatal clinic.
      RESULTS: Being referred to the clinic conferred an 'at risk' status on women.
      Some women welcomed the referral but others experienced it as unsettling. Many
      were unclear about why they had been identified as being at risk or had
      difficulties in accepting the legitimacy of the reason for referral. Women were
      often inadequately informed about why they were referred to the clinic, what they
      could expect and the benefits of attending the clinic over management in the
      community. Although attendance at the clinic was cited as a source of
      reassurance, the reassurance was often made necessary by concern raised by the
      initial referral. CONCLUSIONS: Women's accounts suggest that the interface
      between community and secondary antenatal services needs improvement to minimise
      possible adverse effects from identifying women as being 'at risk' during
      pregnancy.

PMID- 16907937
TI  - Which factors determine the sexual function 1 year after childbirth?
AB  - OBJECTIVE: To evaluate which factors determine sexual activity and satisfaction
      with the sexual relationship 1 year after the first delivery. DESIGN: Prospective
      longitudinal cohort study. SETTING: Ten midwifery practices. POPULATION: Three
      hundred and seventy-seven nulliparous women were included. METHODS: The Maudsley
      Marital Questionnaire is a standardised and validated questionnaire with 15 items
      relating to marital and sexual adjustment, with a nine-point (0-8) scale appended
      to each question. Scores on the sexual scale (MMQ-S) range from 0 to 40. Higher
      scores are indicative of greater dissatisfaction. Sexual intercourse was
      dichotomised into having sexual intercourse or not having sexual intercourse.
      Several obstetric and maternal factors were analysed. MAIN OUTCOME MEASUREMENTS:
      Sexual intercourse at 1 year postpartum and dissatisfaction with the sexual
      relationship as assessed by the MMQ-S scale. RESULTS: In multiple logistic
      regression analysis, the main predictive factor for no sexual intercourse 1 year
      postpartum was no sexual intercourse at 12 weeks of gestation (beta 11.0 [4.01
      30.4]). Women were five times less likely to be sexually active after a
      third/fourth degree anal sphincter tear as compared with women with an intact
      perineum (beta 0.2 [0.04-0.93]). Dissatisfaction with the sexual relationship 1
      year after childbirth, assessed with the MMQ-S scale, is associated with not
      being sexually active at 12 weeks of gestation (beta- 0.208, P= 0.004) and with
      an older maternal age at delivery (beta 0.405, P= 0.032). CONCLUSION: An
      important prognostic factor for dissatisfaction with the sexual relationship 1
      year postpartum was not being sexually active in early pregnancy. Satisfaction
      with the sexual relationship seems not to depend on pregnancy- and parturition
      associated factors.

PMID- 16907938
TI  - Improving the accuracy of estimated blood loss at obstetric haemorrhage using
      clinical reconstructions.
AB  - OBJECTIVES: Following the results of the Confidential Enquiries into Maternal
      Deaths report, which claims two maternal deaths annually in the UK from
      postpartum haemorrhage, our aim was to assess the accuracy of 'visual estimation
      of blood loss' and produce suitable pictorial and written algorithms to aid in
      the recognition and management of massive obstetric haemorrhage. DESIGN:
      Observational study to determine discrepancy between actual blood loss (ABL) and
      estimated blood loss (EBL). SETTING: Teaching hospital. POPULATION: Hundred and
      three obstetricians, anaesthetists, midwives, nurses and healthcare assistants.
      METHODS: Clinical scenarios were reproduced in the form of 12 Objective
      Structured Clinical Examination (OSCE) style stations augmented with known
      volumes of whole blood. Individual staff estimated the blood loss visually and
      recorded their results. Digital photographs were used to produce a pictorial
      'algorithm' suitable for use as a teaching tool in labour ward. MAIN OUTCOME
      MEASURES: Areas of greatest discrepancy between EBL and ABL. RESULTS: Significant
      underestimation of the ABL occurred in 5 of the 12 OSCE stations: 500-ml (50-cm
      diameter) floor spill, 1000-ml (75-cm diameter) floor spill, 1500-ml (100-cm
      diameter) floor spill, 350-ml capacity of soaked 45- x 45-cm large swab and the 2
      l vaginal postpartum haemorrhage on bed/floor. CONCLUSIONS: Accurate visual
      estimation of blood loss is known to facilitate timely resuscitation, minimising
      the risk of disseminated intravascular coagulation and reducing the severity of
      haemorrhagic shock. Participation in clinical reconstructions may encourage early
      diagnosis and prompt treatment of postpartum haemorrhage. Written and pictorial
      guidelines may help all staff working in labour wards.

PMID- 16907939
TI  - Maternal exposure to low levels of ambient air pollution and preterm birth in
      Brisbane, Australia.
AB  - BACKGROUND: [corrected] There is evidence that maternal exposure to ambient air
      pollution during pregnancy is associated with adverse birth outcomes. OBJECTIVE:
      To assess preterm birth (PTB) in relation to maternal exposure to ambient air
      pollution. DESIGN: Retrospective cohort. SETTING: Brisbane, Australia.
      POPULATION: A total of 28,200 singleton live births for the period of 1 July 2000
      to 30 June 2003. METHODS: Average maternal exposure estimates for ambient
      particulate matter (PM(10) and bsp), ozone (O(3)) and nitrogen dioxide were
      calculated over the first 3 months after last menstrual period (LMP) and the last
      3 months prior to birth (individually and combined as trimesters). MAIN OUTCOME
      MEASURES: PTB was defined as gestation <37 weeks and odds ratios (OR) were
      calculated for PTB per interquartile range increase in the maternal exposure
      estimate for each pollutant. Various covariates were controlled for, including
      season of birth. RESULTS: Exposure to PM(10) and O(3) during trimester one was
      associated with an increased risk of PTB (OR = 1.15, 95% CI 1.06-1.25 and OR =
      1.26, 95% CI 1.10-1.45, respectively). The PM(10) exposure effect associated with
      trimester one was strongly related to exposure during the first month post-LMP
      (PM(10), month one; OR = 1.19, 95% CI 1.13-1.26). CONCLUSION: These results
      suggest that maternal exposure to low levels of ambient air pollution is
      associated with PTB.

PMID- 16907940
TI  - The effect of maternal methadone use on the fetal heart pattern: a computerised
      CTG analysis.
AB  - Using a computerised analysis, the cardiotocograph (CTG) from women who use
      methadone (n= 25) when compared with women who do not use methadone (n= 25)
      showed a significant reduction in the fetal heart baseline rate, with a
      significant reduction in number of accelerations and episodes of high variation.
      The short-term variation, number of decelerations and episodes of low variation
      were not different between the two groups. The time taken to meet the
      standardised criteria was not different, and it is possible that a computer
      assisted CTG analysis could be more accurate than a naked eye interpretation.

PMID- 16907941
TI  - The IL-10 -1082G polymorphism is associated with clearance of HPV infection.
AB  - The role of cytokines in protecting against human papillomavirus (HPV) and HPV
      associated disease is not fully understood. We compared the frequency of the
      interleukin (IL)-10 polymorphism (G allele) at position --1082 and the
      distribution of GG/GA/AA genotypes among 116 HPV-positive women, grouped
      according to their cervical cytological profiles, with 119 HPV-negative controls
      with normal smears. No difference was observed in genotype frequency between the
      groups. Among women in the HPV-positive, smear-normal group, who were re-tested
      for HPV after 12 months, there was a significant inverse association between
      presence of at least one variant G allele (high activity) and HPV persistence (OR
      per G allele = 0.082 [95% CI 0.009-0.73], P= 0.001; after controlling for
      ethnicity). This association remained significant after controlling for age,
      smoking and hormonal contraception (OR = 0.028 [95% CI 0.001-0.66], P= 0.001).
      This preliminary study suggests that higher levels of IL-10 may prevent cervical
      neoplasia through their role in eliminating HPV.

PMID- 16907942
TI  - Successful pregnancy following radical trachelectomy and in vitro fertilisation
      with ovum donation.
AB  - This is the first known documented case of a successful pregnancy following
      fertility-preserving radical trachelectomy, ovum donation and in vitro
      fertilisation.

PMID- 16907943
TI  - Breech delivery: the dilemma.

PMID- 16907944
TI  - A career in O&G? No thanks!

PMID- 16907946
TI  - A randomised controlled trial of metronidazole for the prevention of preterm
      birth in women positive for cervicovaginal fetal fibronectin: the PREMET Study.

PMID- 16907948
TI  - How to repair an anal sphincter injury after vaginal delivery: results of a
      randomised controlled trial.

PMID- 16907949
TI  - A prospective randomised controlled trial of the Kiwi Omnicup versus conventional
      ventouse cups for vacuum-assisted vaginal delivery.

PMID- 16907951
TI  - Oral versus self-administered vaginal misoprostol at home before surgical
      termination of pregnancy by Oppegaard et al.

PMID- 16907952
TI  - Does training in obstetric emergencies improve neonatal outcome?

PMID- 16907953
TI  - A comparison of intrapartum automated fetal electrocardiography and conventional
      cardiotocography-a randomised controlled study.

PMID- 16907954
TI  - Sexual function status in women with obstructive sleep apnea syndrome.
AB  - INTRODUCTION: Several co-morbid diseases have been shown to affect sexual
      functions in both genders. In the literature, sexual function status in men with
      obstructive sleep apnea syndrome (OSAS) has been studied; however, sexual
      functions in women with OSAS have not yet been studied. AIMS: In this prospective
      study, we aimed to determine sexual function status in women with OSAS and its
      relationship with the disease parameters of OSAS. METHODS: Women, who were
      diagnosed with OSAS with polysomnography performed in the sleep center of our
      university hospital, formed the study population. Women with any genital
      deformity, postmenopausal women, and women without a regular partner were
      excluded from the study. General demographic properties, medical histories,
      polysomnography parameters, and frequency of intercourse per month were noted for
      each patient. Patients completed the Sexual Function Questionnaire Version 2 (SFQ
      V2) and Epworth Sleepiness Scale. The patients were grouped as mild, moderate,
      and severe OSAS according to the level of respiratory disturbance index (RDI).
      MAIN OUTCOME MEASURES: Scores of sexual function domains were determined from
      SFQ, and their relationships with parameters of polysomnography and demographics
      were studied. RESULTS: Twenty-five patients were included in the study. Mean age
      was 48.1 +/- 2.7 years. All were married with a mean marriage duration of 25.6 +/
      3.3 years. Mean frequency of intercourse per month was 3.3 +/- 1.8. All domains
      of sexual functions except pain and enjoyment significantly decreased with
      increasing severity of OSAS. When we controlled for factors of age and co-morbid
      diseases, correlation analyses showed significant negative correlation between
      levels of RDI and all domains of sexual functions except pain and enjoyment (P <
      0.05). CONCLUSIONS: Obstructive sleep apnea syndrome negatively impacts sexual
      function in women independent of age and associated co-morbid diseases.

PMID- 16907955
TI  - Synthetic prions.
AB  - The prion theory postulates that prions are novel infectious agents that are
      composed largely, if not entirely, of abnormally folded host-encoded prion
      proteins. However, the existence of different prion strains is enigma, if these
      novel infectious agents lack a genetic element, such as a nucleic acid. The best
      proof for this 'protein-only' concept would be the in vitro generation of prions
      from synthetic sources. Indeed, a substantial body of evidence has meanwhile been
      accumulated in favour of this postulate. This mini review recapitulates all
      relevant studies and experimental data on the generation of synthetic prions.

PMID- 16907956
TI  - Validation of rt-PCR assays for molecular characterization of porcine
      teschoviruses and enteroviruses.
AB  - Porcine enteroviruses (PEVs) and teschoviruses (PTVs) are described as causative
      agents of neurological disorders, fertility disorders and dermal lesions of
      swine. Difficulties in the serological detection of these viruses may lead to a
      significant underestimation of infections with clinical symptoms. With the recent
      availability of genome sequence data for all the serotypes, molecular diagnosis
      is a possibility. The present study describes a new approach to molecular
      'serotyping' of PTVs and PEV-B viruses, involving the amplification and
      sequencing of a genomic fragment of the VP1 coding region. A molecular
      characterization of Italian entero-teschovirus isolates was performed using a set
      of previously published and newly designed polymerase chain reaction primers. A
      total of 33 porcine isolates and 10 reference strains were analysed. Porcine
      enterovirus-B samples were first diagnosed as positive for enterovirus by
      amplification of the 5'-non-translated region. Samples were then typed by
      amplification and sequencing of a portion of the VP1 coding region. Porcine
      enterovirus-A and PTVs were detected by a published assay in the 5'-NC region
      that allows them to be differentiated according to the size of amplification
      product, using the same set of primers. For serotype characterization of PTV, we
      evaluated four different regions: the N terminus of the capsid protein VP2, the
      region encoding for RNA-dependent RNA polymerase, and the capsid VP1 and VP4
      regions. The newly designed primers in the VP1 region was proved to be broad in
      range and suitable for serotype assessment and therefore constitute a useful
      diagnostic tool for molecular diagnosis of porcine teschovirus/enterovirus
      strains and for the study of molecular epidemiology and evolution of these
      viruses.

PMID- 16907957
TI  - Long-term administration of a commercial porcine reproductive and respiratory
      syndrome virus (PRRSV)-inactivated vaccine in PRRSV-endemically infected sows.
AB  - The purpose of this study was to investigate the safety and efficacy of a
      commercial European porcine reproductive and respiratory syndrome virus (PRRSV)
      inactivated vaccine after 18-month use in gilts/sows at a farm with high
      seroprevalence. In a farrow-to-finish farm with 1100 sows, all sows and gilts
      were systematically vaccinated with the PRRS-inactivated PROGRESSIS vaccine for a
      period of 18 months. Farm's reproductive and litter characteristics were
      longitudinally recorded for this period and historically compared with those of
      the year prior to vaccination. Serology, employing immunoperoxidase monolayer
      assay, had confirmed a high prevalence of PRRS-specific antibodies in most age
      groups within the farm prior to vaccination. Seroprevalence during the experiment
      ranged between 0% and 100% in weaners and growers, but remained at stable high
      levels (> 93%) in finishing pigs and gilts throughout all 2-year period of
      serology measurements. No local or systemic vaccine side effects were noted
      throughout the trial period. Vaccinations had resulted over time in a significant
      improvement of sow reproductive performance (e.g. reduction of premature
      farrowings, abortions and increase of farrowing rate) and litter characteristics
      (e.g. increase of the number of live born and weaned pigs and decrease of
      stillborn, mummified, weak and splay-legged piglets). It has also been observed
      that the higher the degree of immunization of a sow, the better the improvement
      of her reproductive parameters. Sows after vaccination have shown improved
      characteristics compared to homoparous sows prior to the application of
      vaccinations in the farm.

PMID- 16907958
TI  - Canine distemper virus induces apoptosis through caspase-3 and -8 activation in
      vero cells.
AB  - We investigated the signal-transduction pathway of canine distemper virus
      Onderstepoort (CDV-Ond) vaccine strain-mediated apoptosis in Vero cells. Canine
      distemper virus-Onderstepoort at a multiplicity of infection (MOI) of 0.1 induced
      DNA fragmentation 48 h after infection. Immunofluorescence staining revealed that
      57% +/- 4% of the CDV-N-protein-positive cells were terminal deoxynucleotidyl
      transferase-mediated dUTP nick-end labeling (TUNEL)-positive, and all TUNEL
      positive cells were CDV-N-protein-positive, indicating that CDV-Ond induced
      apoptosis only in the infected cells. We also found that CDV-Ond infection
      induced activation of caspase-3 and caspase-8. In the semi-quantitative reverse
      transcription-polymerase chain reaction assay for apoptosis-related genes, the
      expression of mRNA of the death receptor, Fas, was also increased in CDV-Ond
      infected cells. In contrast, the expressions of Bcl-2 and Bax, regulators for
      intrinsic apoptotic signaling through the mitochondria, did not change. These
      results suggest that CDV-Ond induced apoptosis by activating caspase-3, possibly
      through caspase-8 signaling rather than through p53/Bax-mediated, mitochondrial
      signaling in the infected cells.

PMID- 16907959
TI  - Shedding of porcine circovirus into colostrum of sows.
AB  - The purpose of the present study was to investigate porcine circovirus (PCV)
      shedding into the milk of sows. Colostrum was collected from 33 sows. PCV1 was
      isolated from four of 33 milk whey samples. PCV1 DNA was detected by polymerase
      chain reaction in three of these samples and in three of 10 milk cell samples.
      PCV2 was also isolated and detected from every single milk whey sample. These
      results showed that PCV1 and PCV2 were shed into the milk of sows and suggest
      that PCV can be transmitted to offspring by an oral route through milk.

PMID- 16907960
TI  - Detection of Burkholderia cepacia DNA from artificially infected EDTA-blood and
      lung tissue comparing different DNA isolation methods.
AB  - Bacterial DNA (Burkholderia cepacia) was prepared from artificially infected
      equine ethylenediaminetetraacetic acid (EDTA)-blood and lung tissue by using four
      standard methods (lysis buffer containing proteinase K,
      phenol/chloroform/isoamylalcohol-extraction, microwave-treatment, heat treatment)
      and six commercially available kits (Puregene, High Pure PCR Template Preparation
      Kit, InstaGene, QiaAmp Tissue Kit, DNAzol and Elu-Quik). After a subsequent
      polymerase chain reaction (PCR), their efficacy and sensitivity were compared.
      Concerning the detection limits, the simple lysis with a proteinase K-containing
      buffer led to the best results for EDTA-blood as well as for artificially
      infected lung tissue.

PMID- 16907962
TI  - The occurrence of Campylobacter species in Hungarian broiler chickens from farm
      to slaughter.
AB  - The reported number of human enteric diseases caused by thermotolerant
      campylobacters increased in the last few decades worldwide. The microorganism
      gets into the food chain mostly with poultry meat or meat products. We are not
      aware of the way the campylobacters infect the broiler flocks, and there is
      little information about the real prevalence, about the reaction of
      thermotolerant campylobacters to the environmental factors and about the
      possibilities of elimination of the bacteria from the food chain. As a part of
      the long study, samples were collected from a broiler flock from the first day of
      life to the slaughter of the animals, in summer and in winter. In the summer
      period, at the first two sampling days (days 0 and 12) all of the samples were
      negative. At day 26, one cloaca sample, one sample from the surface of the wall
      near the ventilation aperture and an insect-sample were positive. At day 42, we
      found Campylobacter spp. on every sampling point at the slaughterhouse. In the
      winter period, we could not find Campylobacter spp. either from 0 day old, or
      from 10- and 31-day-old chickens, but we found them at 42 days of age on the
      slaughter plant. At the slaughtering place, 93.3% of the live birds were infected
      with Campylobacter spp., and at the end of the processing line, the infection
      rate was 100%. We could isolate campylobacters from the hands of the workers and
      from the processing environment as well. Out of the positive samples, 95.5% was
      contaminated with Campylobacter jejuni.

PMID- 16907961
TI  - An outbreak of Salmonella Abortusovis abortions in sheep in south Croatia.
AB  - The aim of the study was to give an account of the epidemic of abortions in sheep
      caused by Salmonella enterica ssp. enterica serovar Abortusovis, which occurred
      in Dalmatia, south Croatia, in winter 2003-2004. Five sheep flocks with rate of
      abortion ranging from 22% to 38% during the last-third of gestation were
      examined. Salmonella Abortusovis was isolated from 13 vaginal smears and two
      fetuses. Direct inoculation was found to be superior to pre-enrichment and
      enrichment in selective broth for Salmonella Abortusovis isolation. The isolates
      were biochemically identified, and characterized by serotyping and polymerase
      chain reaction based on the amplification of the IS200 sequence specific for
      Salmonella Abortusovis. A fragment of 900 bp was detected in all Salmonella
      Abortusovis isolates. The sensitivity testing of the isolates, carried out by the
      disk diffusion method and the determination of the minimal inhibitory
      concentrations, resulted in a high sensitivity to almost all antimicrobials used.
      Only two isolates were moderately sensitive to oxytetracycline, whereas one
      isolate showed resistance to streptomycin. Campylobacter fetus ssp. fetus and
      Listeria monocytogenes were excluded as causative agents of abortion in sheep by
      culture testing, and brucellosis, leptospirosis, Q fever and chlamydiosis by
      serological testing.

PMID- 16907963
TI  - Incidences of canine leishmaniasis in an endemic area of southern Italy.
AB  - Canine leishmaniasis (CanL), caused by Leishmania infantum, is widely distributed
      in many Mediterranean countries and is considered endemic in southern and central
      Italy with prevalence reaching up to 48.4%. Determination of the incidence would
      be useful as a measure of the risk of infection, then to evaluate the usefulness
      of control measures and to estimate whether a new focus is autochthonous or
      imported. This study was performed on two sites in the Apulia region of southern
      Italy, namely sites A and B. A total of 262 dogs were included in the evaluation
      of incidence, 94 farm dogs from site A and 168 dogs (92 farm and 76 kennel dogs)
      from site B. The incidence of infection was determined by using two different
      approaches: in site A by means of incidence density rate (IDR); in site B by the
      yearly seroconversion rate. In site A, the IDR was calculated at 4.25% dog-years;
      in site B the yearly incidence rate was of 9.52% (6.5% and 13.1% in farm and
      kennel dogs, respectively). The strength and weakness of the two different
      approaches (i.e. annual monitoring or monthly interval monitoring) for
      calculating the incidence of CanL in an endemic area have been discussed.

PMID- 16907964
TI  - Compliance of young children with ITN protection in rural Burkina Faso.
AB  - BACKGROUND: Insecticide-treated bed nets (ITNs) are known to be highly effective
      in reducing malaria morbidity and mortality. The effectiveness of ITNs is largely
      influenced by behavioural factors and not much is known regarding such factors
      under programme conditions. METHODS: This descriptive study was nested into a
      large ITN effectiveness study in rural Burkina Faso. During two cross-sectional
      surveys in the dry and rainy season of 2003, random samples of young children
      from nine representative villages (n = 180 per survey) were investigated for
      compliance with ITN protection and related behaviour. Data were collected through
      direct observations and through interviews with mothers. RESULTS: ITNs were
      perceived as very important for protection against mosquitoes and malaria
      particularly during the rainy season, but there were problems with their use
      during the dry season. Young children usually slept with their mother under the
      ITN and self-reported compliance was 66% and 98% during dry and rainy season,
      respectively (confirmed by direct observation in 34% and 79%, respectively).
      Important reasons for low compliance during the dry season were high temperatures
      inside houses and problems related to changing sleeping places during the night.
      CONCLUSION: Under programme conditions, compliance with ITN protection in young
      children is sufficient during the rainy season, but is rather low during the hot
      and dry season. Greater emphasis needs to be placed on information/education
      efforts to make people aware of the fact that the risk of contracting malaria may
      persist throughout the year.

PMID- 16907965
TI  - Fungal infection-related mortality versus total mortality as an outcome in trials
      of antifungal agents.
AB  - BACKGROUND: Disease specific mortality is often used as outcome rather than total
      mortality in clinical trials. This approach assumes that the classification of
      cause of death is unbiased. We explored whether use of fungal infection-related
      mortality as outcome rather than total mortality leads to bias in trials of
      antifungal agents in cancer patients. METHODS: As an estimate of bias we used
      relative risk of death in those patients the authors considered had not died from
      fungal infection. Our sample consisted of 69 trials included in four systematic
      reviews of prophylactic or empirical antifungal treatment in patients with cancer
      and neutropenia we have published previously. RESULTS: Thirty trials met the
      inclusion criteria. The trials comprised 6130 patients and 869 deaths, 220 (25%)
      of which were ascribed to fungal infection. The relative risk of death was 0.85
      (95% CI 0.75-0.96) for total mortality, 0.57 (95% CI 0.44-0.74) for fungal
      mortality, and 0.95 (95% CI 0.82-1.09) for mortality among those who did not die
      from fungal infection. CONCLUSION: We could not support the hypothesis that use
      of disease specific mortality introduces bias in antifungal trials on cancer
      patients as our estimate of the relative risk for mortality in those who survived
      the fungal infection was not increased. We conclude that it seems to be reliable
      to use fungal mortality as the primary outcome in trials of antifungal agents.
      Data on total mortality should be reported as well, however, to guard against the
      possible introduction of harmful treatments.

PMID- 16907966
TI  - Soy isoflavones increase preprandial peptide YY (PYY), but have no effect on
      ghrelin and body weight in healthy postmenopausal women.
AB  - BACKGROUND: Soy isoflavones show structural and functional similarities to
      estradiol. Available data indicate that estradiol and estradiol-like components
      may interact with gut "satiety hormones" such as peptide YY (PYY) and ghrelin,
      and thus influence body weight. In a randomized, double-blind, placebo
      controlled, cross-over trial with 34 healthy postmenopausal women (59 +/- 6
      years, BMI: 24.7 +/- 2.8 kg/m2), isoflavone-enriched cereal bars (50 mg
      isoflavones/day; genistein to daidzein ratio 2:1) or non-isoflavone-enriched
      control bars were consumed for 8 weeks (wash-out period: 8-weeks). Seventeen of
      the subjects were classified as equol producers. Plasma concentrations of ghrelin
      and PYY, as well as energy intake and body weight were measured at baseline and
      after four and eight weeks of each intervention arm. RESULTS: Body weight
      increased in both treatment periods (isoflavone: 0.40 +/- 0.94 kg, P < 0.001;
      placebo: 0.66 +/- 0.87 kg, P = 0.018), with no significant difference between
      treatments. No significant differences in energy intake were observed (P =
      0.634). PYY significantly increased during isoflavone treatment (51 +/- 2 pmol/L
      vs. 55 +/- 2 pmol/L), but not during placebo (52 +/- 3 pmol/L vs. 50 +/- 2
      pmol/L), (P = 0.010 for treatment differences, independent of equol production).
      Baseline plasma ghrelin was significantly lower in equol producers (110 +/- 16
      pmol/L) than in equol non-producers (162 +/- 17 pmol/L; P = 0.025). CONCLUSION:
      Soy isoflavone supplementation for eight weeks did not significantly reduce
      energy intake or body weight, even though plasma PYY increased during isoflavone
      treatment. Ghrelin remained unaffected by isoflavone treatment. A larger and more
      rigorous appetite experiment might detect smaller differences in energy intake
      after isoflavone consumption. However, the results of the present study do not
      indicate that increased PYY has a major role in the regulation of body weight, at
      least in healthy postmenopausal women.

PMID- 16907967
TI  - Critical points of DNA quantification by real-time PCR--effects of DNA extraction
      method and sample matrix on quantification of genetically modified organisms.
AB  - BACKGROUND: Real-time PCR is the technique of choice for nucleic acid
      quantification. In the field of detection of genetically modified organisms
      (GMOs) quantification of biotech products may be required to fulfil legislative
      requirements. However, successful quantification depends crucially on the quality
      of the sample DNA analyzed. Methods for GMO detection are generally validated on
      certified reference materials that are in the form of powdered grain material,
      while detection in routine laboratories must be performed on a wide variety of
      sample matrixes. Due to food processing, the DNA in sample matrixes can be
      present in low amounts and also degraded. In addition, molecules of plant origin
      or from other sources that affect PCR amplification of samples will influence the
      reliability of the quantification. Further, the wide variety of sample matrixes
      presents a challenge for detection laboratories. The extraction method must
      ensure high yield and quality of the DNA obtained and must be carefully selected,
      since even components of DNA extraction solutions can influence PCR reactions.
      GMO quantification is based on a standard curve, therefore similarity of PCR
      efficiency for the sample and standard reference material is a prerequisite for
      exact quantification. Little information on the performance of real-time PCR on
      samples of different matrixes is available. RESULTS: Five commonly used DNA
      extraction techniques were compared and their suitability for quantitative
      analysis was assessed. The effect of sample matrix on nucleic acid quantification
      was assessed by comparing 4 maize and 4 soybean matrixes. In addition 205 maize
      and soybean samples from routine analysis were analyzed for PCR efficiency to
      assess variability of PCR performance within each sample matrix. Together with
      the amount of DNA needed for reliable quantification, PCR efficiency is the
      crucial parameter determining the reliability of quantitative results, therefore
      it was chosen as the primary criterion by which to evaluate the quality and
      performance on different matrixes and extraction techniques. The effect of PCR
      efficiency on the resulting GMO content is demonstrated. CONCLUSION: The crucial
      influence of extraction technique and sample matrix properties on the results of
      GMO quantification is demonstrated. Appropriate extraction techniques for each
      matrix need to be determined to achieve accurate DNA quantification.
      Nevertheless, as it is shown that in the area of food and feed testing matrix
      with certain specificities is impossible to define strict quality controls need
      to be introduced to monitor PCR. The results of our study are also applicable to
      other fields of quantitative testing by real-time PCR.

PMID- 16907968
TI  - Literacy and health outcomes: a cross-sectional study in 1002 adults with
      diabetes.
AB  - BACKGROUND: Inconsistent findings reported in the literature contribute to the
      lack of complete understanding of the association of literacy with health
      outcomes. We evaluated the association between literacy, physiologic control and
      diabetes complications among adults with diabetes. METHODS: A cross-sectional
      study of 1,002 English speaking adults with diabetes, randomly selected from the
      Vermont Diabetes Information System, a cluster-randomized trial of a diabetes
      decision support system in a region-wide sample of primary care practices was
      conducted between July 2003 and March 2005. Literacy was assessed by the Short
      Test of Functional Health Literacy in Adults. Outcome measures included glycated
      hemoglobin, low density lipoprotein, blood pressure and self-reported
      complications. RESULTS: After adjusting for sociodemographic characteristics,
      duration of diabetes, diabetes education, depression, alcohol use, and medication
      use we did not find a significant association between literacy and glycemic
      control (beta coefficent,+ 0.001; 95% confidence interval [CI], -0.01 to +0.01; P
      = .88), systolic blood pressure (beta coefficent, +0.08; 95% CI, -0.10 to +0.26;
      P = .39), diastolic blood pressure (beta coefficent, -0.03; 95% CI, -0.12 to
      +0.07, P = .59), or low density lipoprotein (beta coefficent, +0.04; 95% CI, 
      0.27 to +0.36, P = .77. We found no association between literacy and report of
      diabetes complications. CONCLUSION: These findings suggest that literacy, as
      measured by the S-TOFHLA, is not associated with glycated hemoglobin, blood
      pressure, lipid levels or self-reported diabetes complications in a cross
      sectional study of older adults with diabetes under relatively good glycemic
      control. Additional studies to examine the optimal measurement of health literacy
      and its relationship to health outcomes over time are needed.

PMID- 16907969
TI  - Managing health professional migration from sub-Saharan Africa to Canada: a
      stakeholder inquiry into policy options.
AB  - BACKGROUND: Canada is a major recipient of foreign-trained health professionals,
      notably physicians from South Africa and other sub-Saharan African countries.
      Nurse migration from these countries, while comparatively small, is rising.
      African countries, meanwhile, have a critical shortage of professionals and a
      disproportionate burden of disease. What policy options could Canada pursue that
      balanced the right to health of Africans losing their health workers with the
      right of these workers to seek migration to countries such as Canada? METHODS: We
      interviewed a small sample of emigre South African physicians (n = 7) and a
      larger purposive sample of representatives of Canadian federal, provincial,
      regional and health professional departments/organizations (n = 25); conducted a
      policy colloquium with stakeholder organizations (n = 21); and undertook new
      analyses of secondary data to determine recent trends in health human resource
      flows between sub-Saharan Africa and Canada. RESULTS: Flows from sub-Saharan
      Africa to Canada have increased since the early 1990s, although they may now have
      peaked for physicians from South Africa. Reasons given for this flow are
      consistent with other studies of push/pull factors. Of 8 different policy options
      presented to study participants, only one received unanimous strong support
      (increasing domestic self-sufficiency), one other received strong support
      (increased health system strengthening in source country), two others mixed
      support (voluntary codes on ethical recruitment, bilateral or multilateral
      agreements to manage flows) and four others little support or complete rejection
      (increased training of auxiliary health workers in Africa ineligible for
      licensing in Canada, bonding, reparation payments for training-cost losses and
      restrictions on immigration of health professionals from critically underserved
      countries). CONCLUSION: Reducing pull factors by improving domestic supply and
      reducing push factors by strengthening source country health systems have the
      greatest policy traction in Canada. The latter, however, is not perceived as
      presently high on Canadian stakeholder organizations' policy agendas, although
      support for it could grow if it is promoted. Canada is not seen as "actively'
      recruiting" ("poaching") health workers from developing countries. Recent changes
      in immigration policy, ongoing advertising in southern African journals and
      promotion of migration by private agencies, however, blurs the distinction
      between active and passive recruitment.

PMID- 16907970
TI  - A general pipeline for the development of anchor markers for comparative genomics
      in plants.
AB  - BACKGROUND: Complete or near-complete genomic sequence information is presently
      only available for a few plant species representing a large phylogenetic
      diversity among plants. In order to effectively transfer this information to
      species lacking sequence information, comparative genomic tools need to be
      developed. Molecular markers permitting cross-species mapping along co-linear
      genomic regions are central to comparative genomics. These "anchor" markers,
      defining unique loci in genetic linkage maps of multiple species, are gene-based
      and possess a number of features that make them relatively sparse. To identify
      potential anchor marker sequences more efficiently, we have established an
      automated bioinformatic pipeline that combines multi-species Expressed Sequence
      Tags (EST) and genome sequence data. RESULTS: Taking advantage of sequence data
      from related species, the pipeline identifies evolutionarily conserved sequences
      that are likely to define unique orthologous loci in most species of the same
      phylogenetic clade. The key features are the identification of evolutionarily
      conserved sequences followed by automated design of intron-flanking Polymerase
      Chain Reaction (PCR) primer pairs. Polymorphisms can subsequently be identified
      by size- or sequence variation of PCR products, amplified from mapping parents or
      populations. We illustrate our procedure in legumes and grasses and exemplify its
      application in legumes, where model plant studies and the genome- and EST
      sequence data available have a potential impact on the breeding of crop species
      and on our understanding of the evolution of this large and diverse family.
      CONCLUSION: We provide a database of 459 candidate anchor loci which have the
      potential to serve as map anchors in more than 18,000 legume species, a number of
      which are of agricultural importance. For grasses, the database contains 1335
      candidate anchor loci. Based on this database, we have evaluated 76 candidate
      anchor loci with respect to marker development in legume species with no sequence
      information available, demonstrating the validity of this approach.

PMID- 16907971
TI  - The origin of introns and their role in eukaryogenesis: a compromise solution to
      the introns-early versus introns-late debate?
AB  - BACKGROUND: Ever since the discovery of 'genes in pieces' and mRNA splicing in
      eukaryotes, origin and evolution of spliceosomal introns have been considered
      within the conceptual framework of the 'introns early' versus 'introns late'
      debate. The 'introns early' hypothesis, which is closely linked to the so-called
      exon theory of gene evolution, posits that protein-coding genes were interrupted
      by numerous introns even at the earliest stages of life's evolution and that
      introns played a major role in the origin of proteins by facilitating
      recombination of sequences coding for small protein/peptide modules. Under this
      scenario, the absence of spliceosomal introns in prokaryotes is considered to be
      a result of "genome streamlining". The 'introns late' hypothesis counters that
      spliceosomal introns emerged only in eukaryotes, and moreover, have been inserted
      into protein-coding genes continuously throughout the evolution of eukaryotes.
      Beyond the formal dilemma, the more substantial side of this debate has to do
      with possible roles of introns in the evolution of eukaryotes. RESULTS: I argue
      that several lines of evidence now suggest a coherent solution to the introns
      early versus introns-late debate, and the emerging picture of intron evolution
      integrates aspects of both views although, formally, there seems to be no support
      for the original version of introns-early. Firstly, there is growing evidence
      that spliceosomal introns evolved from group II self-splicing introns which are
      present, usually, in small numbers, in many bacteria, and probably, moved into
      the evolving eukaryotic genome from the alpha-proteobacterial progenitor of the
      mitochondria. Secondly, the concept of a primordial pool of 'virus-like' genetic
      elements implies that self-splicing introns are among the most ancient genetic
      entities. Thirdly, reconstructions of the ancestral state of eukaryotic genes
      suggest that the last common ancestor of extant eukaryotes had an intron-rich
      genome. Thus, it appears that ancestors of spliceosomal introns, indeed, have
      existed since the earliest stages of life's evolution, in a formal agreement with
      the introns-early scenario. However, there is no evidence that these ancient
      introns ever became widespread before the emergence of eukaryotes, hence, the
      central tenet of introns-early, the role of introns in early evolution of
      proteins, has no support. However, the demonstration that numerous introns
      invaded eukaryotic genes at the outset of eukaryotic evolution and that
      subsequent intron gain has been limited in many eukaryotic lineages implicates
      introns as an ancestral feature of eukaryotic genomes and refutes radical
      versions of introns-late. Perhaps, most importantly, I argue that the intron
      invasion triggered other pivotal events of eukaryogenesis, including the
      emergence of the spliceosome, the nucleus, the linear chromosomes, the
      telomerase, and the ubiquitin signaling system. This concept of eukaryogenesis,
      in a sense, revives some tenets of the exon hypothesis, by assigning to introns
      crucial roles in eukaryotic evolutionary innovation. CONCLUSION: The scenario of
      the origin and evolution of introns that is best compatible with the results of
      comparative genomics and theoretical considerations goes as follows: self
      splicing introns since the earliest stages of life's evolution--numerous
      spliceosomal introns invading genes of the emerging eukaryote during
      eukaryogenesis--subsequent lineage-specific loss and gain of introns. The intron
      invasion, probably, spawned by the mitochondrial endosymbiont, might have
      critically contributed to the emergence of the principal features of the
      eukaryotic cell. This scenario combines aspects of the introns-early and introns
      late views. REVIEWERS: this article was reviewed by W. Ford Doolittle, James
      Darnell (nominated by W. Ford Doolittle), William Martin, and Anthony Poole.

PMID- 16907972
TI  - Evaluation of an interactive case simulation system in dermatology and
      venereology for medical students.
AB  - BACKGROUND: Most of the many computer resources used in clinical teaching of
      dermatology and venereology for medical undergraduates are information-oriented
      and focus mostly on finding a "correct" multiple-choice alternative or free-text
      answer. We wanted to create an interactive computer program, which facilitates
      not only factual recall but also clinical reasoning. METHODS: Through continuous
      interaction with students, a new computerised interactive case simulation system,
      NUDOV, was developed. It is based on authentic cases and contains images of real
      patients, actors and healthcare providers. The student selects a patient and
      proposes questions for medical history, examines the skin, and suggests
      investigations, diagnosis, differential diagnoses and further management.
      Feedback is given by comparing the user's own suggestions with those of a
      specialist. In addition, a log file of the student's actions is recorded. The
      program includes a large number of images, video clips and Internet links. It was
      evaluated with a student questionnaire and by randomising medical students to
      conventional teaching (n = 85) or conventional teaching plus NUDOV (n = 31) and
      comparing the results of the two groups in a final written examination. RESULTS:
      The questionnaire showed that 90% of the NUDOV students stated that the program
      facilitated their learning to a large/very large extent, and 71% reported that
      extensive working with authentic computerised cases made it easier to understand
      and learn about diseases and their management. The layout, user-friendliness and
      feedback concept were judged as good/very good by 87%, 97%, and 100%,
      respectively. Log files revealed that the students, in general, worked with each
      case for 60-90 min. However, the intervention group did not score significantly
      better than the control group in the written examination. CONCLUSION: We created
      a computerised case simulation program allowing students to manage patients in a
      non-linear format supporting the clinical reasoning process. The student gets
      feedback through comparison with a specialist, eliminating the need for external
      scoring or correction. The model also permits discussion of case processing,
      since all transactions are stored in a log file. The program was highly
      appreciated by the students, but did not significantly improve their performance
      in the written final examination.

PMID- 16907973
TI  - Affordable flow cytometry for enumeration of absolute CD4+ T-lymphocytes to
      identify subtype C HIV-1 infected adults requiring antiretroviral therapy (ART)
      and monitoring response to ART in a resource-limited setting.
AB  - BACKGROUND: The World Health Organization (WHO)'s "3 x 5 program" has spurred
      efforts to place 3 million people on combination antiretroviral therapy (ART) for
      treatment of AIDS in resource-limited countries. Paradoxically, the cost of CD4+
      T-lymphocyte count essential for decision-making to commence HIV positive adults
      on ART as well as for monitoring responses to ART remains unaffordable in most
      resource-limited countries. Thus, low-cost methods for enumerating CD4+ T
      lymphocyte are urgently needed. OBJECTIVE: To evaluate Cyflow cytometry (Cyflow
      SL, Partec, Munster, Germany) for enumeration of absolute CD4+ T-lymphocyte in
      subtype C HIV-1 seropositive subjects using FACSCount (Becton and Dickinson,
      Immunocytometry Systems, San Jose, CA, USA) as the "predicate method". METHODS: A
      total of 150 HIV-1 seropositive subjects were included in the evaluation
      exercise. Fifty-eight specimens were collected from pregnant HIV-1 seropositive
      women (subtype C drug resistance study). Twenty-seven specimens were collected
      from women and their spouses with AIDS followed in a Duke ART study to assess the
      immunologic and virologic responses to generic ART, comprising Stavudine,
      Lamivudine and Nevirapine (Stalanev, Varichem Labs, Harare, Zimbabwe). Sixty-five
      specimens were collected from AIDS patients enrolled in an ongoing Kaposi Sarcoma
      (KS) study to investigate impact of ART on KS progression. Enumeration of CD4+ T
      lymphocytes using FACSCount is routinely conducted for all the three studies. The
      Medical Research Council of Zimbabwe and Medicines Control Authority of Zimbabwe
      approved the studies. Whole blood was collected in EDTA vacutainer tubes and
      aliquoted into two tubes (200 microL in each). CD4+ T-lymphocyte counts were
      enumerated using a Cyflow counter, in the Department of Immunology and a
      FACSCount in the Department of Obstetrics and Gynaecology within 6 hours of
      phlebotomy following manufacturers' instructions. RESULTS: Using linear
      regression analysis, there was a very strong correlation (R = 0.991) between the
      overall CD4+ T-lymphocyte counts obtained by FACSCount and those obtained by
      Cyflow. When data analysis was stratified by study groups, there was a strong
      correlation between the FACSCount and Cyflow CD4+ T-lymphocyte counts from
      subjects in the three independent studies; Subtype C resistance (R2 = 0.987),
      Duke ART (R2 = 0.980) and KS (R2 = 0.994), Table 1. Using Bland-Altman plots, the
      overall, absolute CD4+ T lymphocytes obtained by the two methods were in
      excellent agreement (mean difference 1.21, 95% Confidence Interval {CI): -2.1 to
      3.3). For the 0-250 CD4+ T-lymphocytes range, the CD4 counts obtained using
      FACSCount were also in good agreement with those obtained using Cyflow counter
      (mean difference = 2.6 cells/microL, 95% CI: -1.1 to 6.3). Similarly, in the 251
      500 (mean difference 1.0, cells/microL, 95% CI: -3.7 to 5.6) and the 501-1200
      (mean difference = 0.29 cells/microL, 95% CI: -8.1 to 8.7) CD4 T-lymphocytes
      range, good agreement was observed. CONCLUSION: The Cyflow counter is as accurate
      as the FACSCount in enumerating absolute CD4+ T-lymphocytes in the range 1-1200
      cells/muL. Cyflow cytometry is relatively affordable, easy to use technology that
      is useful not only in identifying HIV seropositive individuals who require ART
      but also for monitoring immunologic responses to ART.

PMID- 16907974
TI  - MRCP compared to diagnostic ERCP for diagnosis when biliary obstruction is
      suspected: a systematic review.
AB  - BACKGROUND: Magnetic resonance cholangiopancreatography (MRCP) is an alternative
      to diagnostic endoscopic retrograde cholangiopancreatography (ERCP) for
      investigating biliary obstruction. The use of MRCP, a non-invasive procedure, may
      prevent the use of unnecessary invasive procedures. The aim of the study was to
      compare the findings of MRCP with those of ERCP by the computation of accuracy
      statistics. METHODS: Thirteen electronic bibliographic databases, covering
      biomedical, science, health economics and grey literature were searched. A
      systematic review of studies comparing MRCP to diagnostic ERCP in patients with
      suspected biliary obstruction was conducted. Sensitivity, specificity, likelihood
      ratios, acceptability and adverse events were reported. RESULTS: 25 studies were
      identified reporting several conditions including choledocholithiasis (18
      studies), malignancy (four studies), obstruction (three studies), stricture (two
      studies) and dilatation (five studies). Three of the 18 studies reporting
      choledocholithiasis were excluded from the analysis due to lack of data, or
      differences in study design. The sensitivity for the 15 studies of
      choledocholithiasis ranged from 0.50 to 1.00 while specificity ranged from 0.83
      to 1.00. The positive likelihood ratio ranged: from 5.44-47.72 and the negative
      likelihood ratio for the 15 studies ranged from 0.00-0.51. Significant
      heterogeneity was found across the 15 studies so the sensitivities and
      specificities were summarised by a Receiver Operating Characteristic (ROC) curve.
      For malignancy, sensitivity ranged from 0.81 to 0.94 and specificity from 0.92 to
      1.00. Positive likelihood ratios ranged from 10.12 to 43 and negative likelihood
      ratios ranged from 0.15 to 0.21, although these estimates were less reliable.
      CONCLUSION: MRCP is a comparable diagnostic investigation in comparison to ERCP
      for diagnosing biliary obstruction.

PMID- 16907975
TI  - A novel data mining method to identify assay-specific signatures in functional
      genomic studies.
AB  - BACKGROUND: The highly dimensional data produced by functional genomic (FG)
      studies makes it difficult to visualize relationships between gene products and
      experimental conditions (i.e., assays). Although dimensionality reduction methods
      such as principal component analysis (PCA) have been very useful, their
      application to identify assay-specific signatures has been limited by the lack of
      appropriate methodologies. This article proposes a new and powerful PCA-based
      method for the identification of assay-specific gene signatures in FG studies.
      RESULTS: The proposed method (PM) is unique for several reasons. First, it is the
      only one, to our knowledge, that uses gene contribution, a product of the loading
      and expression level, to obtain assay signatures. The PM develops and exploits
      two types of assay-specific contribution plots, which are new to the application
      of PCA in the FG area. The first type plots the assay-specific gene contribution
      against the given order of the genes and reveals variations in distribution
      between assay-specific gene signatures as well as outliers within assay groups
      indicating the degree of importance of the most dominant genes. The second type
      plots the contribution of each gene in ascending or descending order against a
      constantly increasing index. This type of plots reveals assay-specific gene
      signatures defined by the inflection points in the curve. In addition, sharp
      regions within the signature define the genes that contribute the most to the
      signature. We proposed and used the curvature as an appropriate metric to
      characterize these sharp regions, thus identifying the subset of genes
      contributing the most to the signature. Finally, the PM uses the full dataset to
      determine the final gene signature, thus eliminating the chance of gene exclusion
      by poor screening in earlier steps. The strengths of the PM are demonstrated
      using a simulation study, and two studies of real DNA microarray data--a study of
      classification of human tissue samples and a study of E. coli cultures with
      different medium formulations. CONCLUSION: We have developed a PCA-based method
      that effectively identifies assay-specific signatures in ranked groups of genes
      from the full data set in a more efficient and simplistic procedure than current
      approaches. Although this work demonstrates the ability of the PM to identify
      assay-specific signatures in DNA microarray experiments, this approach could be
      useful in areas such as proteomics and metabolomics.

PMID- 16907976
TI  - Comprehensive quality control utilizing the prehybridization third-dye image
      leads to accurate gene expression measurements by cDNA microarrays.
AB  - BACKGROUND: Gene expression profiling using microarrays has become an important
      genetic tool. Spotted arrays prepared in academic labs have the advantage of low
      cost and high design and content flexibility, but are often limited by their
      susceptibility to quality control (QC) issues. Previously, we have reported a
      novel 3-color microarray technology that enabled array fabrication QC. In this
      report we further investigated its advantage in spot-level data QC. RESULTS: We
      found that inadequate amount of bound probes available for hybridization led to
      significant, gene-specific compression in ratio measurements, increased data
      variability, and printing pin dependent heterogeneities. The impact of such
      problems can be captured through the definition of quality scores, and
      efficiently controlled through quality-dependent filtering and normalization. We
      compared gene expression measurements derived using our data processing pipeline
      with the known input ratios of spiked in control clones, and with the
      measurements by quantitative real time RT-PCR. In each case, highly linear
      relationships (R2 > 0.94) were observed, with modest compression in the
      microarray measurements (correction factor < 1.17). CONCLUSION: Our microarray
      analytical and technical advancements enabled a better dissection of the sources
      of data variability and hence a more efficient QC. With that highly accurate gene
      expression measurements can be achieved using the cDNA microarray technology.

PMID- 16907978
TI  - Factors associated with nosocomial SARS-CoV transmission among healthcare workers
      in Hanoi, Vietnam, 2003.
AB  - BACKGROUND: In March of 2003, an outbreak of Severe Acute Respiratory Syndrome
      (SARS) occurred in Northern Vietnam. This outbreak began when a traveler arriving
      from Hong Kong sought medical care at a small hospital (Hospital A) in Hanoi,
      initiating a serious and substantial transmission event within the hospital, and
      subsequent limited spread within the community. METHODS: We surveyed Hospital A
      personnel for exposure to the index patient and for symptoms of disease during
      the outbreak. Additionally, serum specimens were collected and assayed for
      antibody to SARS-associated coronavirus (SARS-CoV) antibody and job-specific
      attack rates were calculated. A nested case-control analysis was performed to
      assess risk factors for acquiring SARS-CoV infection. RESULTS: One hundred and
      fifty-three of 193 (79.3%) clinical and non-clinical staff consented to
      participate. Excluding job categories with < 3 workers, the highest SARS attack
      rates occurred among nurses who worked in the outpatient and inpatient general
      wards (57.1, 47.4%, respectively). Nurses assigned to the operating
      room/intensive care unit, experienced the lowest attack rates (7.1%) among all
      clinical staff. Serologic evidence of SARS-CoV infection was detected in 4
      individuals, including 2 non-clinical workers, who had not previously been
      identified as SARS cases; none reported having had fever or cough. Entering the
      index patient's room and having seen (viewed) the patient were the behaviors
      associated with highest risk for infection by univariate analysis (odds ratios
      20.0, 14.0; 95% confidence intervals 4.1-97.1, 3.6-55.3, respectively).
      CONCLUSION: This study highlights job categories and activities associated with
      increased risk for SARS-CoV infection and demonstrates that a broad diversity of
      hospital workers may be vulnerable during an outbreak. These findings may help
      guide recommendations for the protection of vulnerable occupational groups and
      may have implications for other respiratory infections such as influenza.

PMID- 16907977
TI  - The potential risks of nanomaterials: a review carried out for ECETOC.
AB  - During the last few years, research on toxicologically relevant properties of
      engineered nanoparticles has increased tremendously. A number of international
      research projects and additional activities are ongoing in the EU and the US,
      nourishing the expectation that more relevant technical and toxicological data
      will be published. Their widespread use allows for potential exposure to
      engineered nanoparticles during the whole lifecycle of a variety of products.
      When looking at possible exposure routes for manufactured Nanoparticles,
      inhalation, dermal and oral exposure are the most obvious, depending on the type
      of product in which Nanoparticles are used. This review shows that (1)
      Nanoparticles can deposit in the respiratory tract after inhalation. For a number
      of nanoparticles, oxidative stress-related inflammatory reactions have been
      observed. Tumour-related effects have only been observed in rats, and might be
      related to overload conditions. There are also a few reports that indicate uptake
      of nanoparticles in the brain via the olfactory epithelium. Nanoparticle
      translocation into the systemic circulation may occur after inhalation but
      conflicting evidence is present on the extent of translocation. These findings
      urge the need for additional studies to further elucidate these findings and to
      characterize the physiological impact. (2) There is currently little evidence
      from skin penetration studies that dermal applications of metal oxide
      nanoparticles used in sunscreens lead to systemic exposure. However, the question
      has been raised whether the usual testing with healthy, intact skin will be
      sufficient. (3) Uptake of nanoparticles in the gastrointestinal tract after oral
      uptake is a known phenomenon, of which use is intentionally made in the design of
      food and pharmacological components. Finally, this review indicates that only few
      specific nanoparticles have been investigated in a limited number of test systems
      and extrapolation of this data to other materials is not possible. Air pollution
      studies have generated indirect evidence for the role of combustion derived
      nanoparticles (CDNP) in driving adverse health effects in susceptible groups.
      Experimental studies with some bulk nanoparticles (carbon black, titanium
      dioxide, iron oxides) that have been used for decades suggest various adverse
      effects. However, engineered nanomaterials with new chemical and physical
      properties are being produced constantly and the toxicity of these is unknown.
      Therefore, despite the existing database on nanoparticles, no blanket statements
      about human toxicity can be given at this time. In addition, limited
      ecotoxicological data for nanomaterials precludes a systematic assessment of the
      impact of Nanoparticles on ecosystems.

PMID- 16907980
TI  - Mixing patterns and the spread of close-contact infectious diseases.
AB  - Surprisingly little is known regarding the human mixing patterns relevant to the
      spread of close-contact infections, such as measles, influenza and meningococcal
      disease. This study aims to estimate the number of partnerships that individuals
      make, their stability and the degree to which mixing is assortative with respect
      to age. We defined four levels of putative at-risk events from casual (physical
      contact without conversation) to intimate (contact of a sexual nature), and asked
      university student volunteers to record details on those they contacted at these
      levels on three separate days. We found that intimate contacts are stable over
      short time periods whereas there was no evidence of repeat casual contacts with
      the same individuals. The contacts were increasingly assortative as intimacy
      increased. Such information will aid the development and parameterisation of
      models of close contact diseases, and may have direct use in outbreak
      investigations.

PMID- 16907979
TI  - Genetic diversity of Plasmodium vivax in Kolkata, India.
AB  - BACKGROUND: Plasmodium vivax malaria accounts for approximately 60% of malaria
      cases in Kolkata, India. There has been limited information on the genotypic
      polymorphism of P. vivax in this malaria endemic area. Three highly polymorphic
      and single copy genes were selected for a study of genetic diversity in Kolkata
      strains. METHODS: Blood from 151 patients with P. vivax infection diagnosed in
      Kolkata between April 2003 and September 2004 was genotyped at three polymorphic
      loci: the P. vivax circumsporozoite protein (pvcs), the merozoite surface protein
      1 (pvmsp1) and the merozoite surface protein 3-alpha (pvmsp3-alpha). RESULTS:
      Analysis of these three genetic markers revealed that P. vivax populations in
      Kolkata are highly diverse. A large number of distinguishable alleles were found
      from three genetic markers: 11 for pvcs, 35 for pvmsp1 and 37 for pvmsp3-alpha.
      These were, in general, randomly distributed amongst the isolates. Among the 151
      isolates, 142 unique genotypes were detected the commonest genotype at a
      frequency of less than 2% (3/151). The overall rate of mixed genotype infections
      was 10.6%. CONCLUSION: These results indicate that the P. vivax parasite
      population is highly diverse in Kolkata, despite the low level of transmission.
      The genotyping protocols used in this study may be useful for differentiating re
      infection from relapse and recrudescence in studies assessing of malarial drug
      efficacy in vivax malaria.

PMID- 16907981
TI  - Swiss residents' arguments for and against a career in medicine.
AB  - BACKGROUND: In some Western countries, the medical profession is continuously
      losing prestige, doctors are claiming of high demands, low rewards, and difficult
      structural working conditions. This study aimed to investigate the arguments
      given by Swiss residents for and against a career in medicine. METHODS: As part
      of a prospective cohort study of Swiss medical school graduates on career
      development, 567 fourth-year residents were asked to answer the free-response
      item of what arguments there still were in favour of or against a career in
      medicine. They also indicated whether they would choose the medical profession
      all over again (yes/no). The statements were transcribed, content categories
      inductively formulated, and their descriptions written down in a code manual.
      Arguments were encoded according to the code manual and assigned to eight content
      categories (Mayring's content analysis). Frequency distributions were given for
      categories and tested with Chi2-tests for differences in gender, speciality
      fields, and whether or not the respondent would again choose a career in
      medicine. RESULTS: The 567 participants made 1,640 statements in favour of and
      1,703 statements against a career in medicine. The content analysis of the
      residents' answers yielded eight categories with arguments both for and against a
      career in medicine. Of all "statements for" responses, 70% fell into the two top
      ranking categories of Personal experiences in day-to-day working life (41.2%) and
      Interpersonal experiences in professional relationships (28.8%). The top-ranking
      category of the "statements against" arguments was General work-related
      structural conditions (32%), followed by Social prestige and health-policy
      aspects (21%). Main arguments in favour of a career in medicine were
      interdisciplinary challenge, combination of basic sciences and interpersonal
      concerns, helping suffering people, guarantee of a secure job; arguments against
      comprised high workload, time pressure, emotional stress, poorly structured
      continuing education, increasing bureaucracy, work-life imbalance, low income,
      and decreasing social prestige. The statements revealed few differences depending
      on gender, medical field, and attitude towards choosing the medical profession
      again; one out of five young doctors would not do so. CONCLUSION: Residents'
      chief complaint is deteriorating structural working conditions, including
      unfavourable work-life balance. Making medicine an attractive profession again
      will require sustainable changes in health-policy framework and social reward.

PMID- 16907983
TI  - Measuring specialization in species interaction networks.
AB  - BACKGROUND: Network analyses of plant-animal interactions hold valuable
      biological information. They are often used to quantify the degree of
      specialization between partners, but usually based on qualitative indices such as
      'connectance' or number of links. These measures ignore interaction frequencies
      or sampling intensity, and strongly depend on network size. RESULTS: Here we
      introduce two quantitative indices using interaction frequencies to describe the
      degree of specialization, based on information theory. The first measure (d')
      describes the degree of interaction specialization at the species level, while
      the second measure (H2') characterizes the degree of specialization or
      partitioning among two parties in the entire network. Both indices are
      mathematically related and derived from Shannon entropy. The species-level index
      d' can be used to analyze variation within networks, while H2' as a network-level
      index is useful for comparisons across different interaction webs. Analyses of
      two published pollinator networks identified differences and features that have
      not been detected with previous approaches. For instance, plants and pollinators
      within a network differed in their average degree of specialization (weighted
      mean d'), and the correlation between specialization of pollinators and their
      relative abundance also differed between the webs. Rarefied sampling effort in
      both networks and null model simulations suggest that H2' is not affected by
      network size or sampling intensity. CONCLUSION: Quantitative analyses reflect
      properties of interaction networks more appropriately than previous qualitative
      attempts, and are robust against variation in sampling intensity, network size
      and symmetry. These measures will improve our understanding of patterns of
      specialization within and across networks from a broad spectrum of biological
      interactions.

PMID- 16907982
TI  - The time course of subsequent hospitalizations and associated costs in survivors
      of an ischemic stroke in Canada.
AB  - BACKGROUND: Documentation of the hospitalizations rates following a stroke
      provides the inputs required for planning health services and to evaluate the
      economic efficiency of any new therapies. METHODS: Hospitalization rates by cause
      were examined using administrative data on 18,695 patients diagnosed with
      ischemic stroke (first or subsequent, excluding transient ischemic attack) in
      Saskatchewan, Canada between 1990 and 1995. Medical history was available
      retrospectively to January 1980 and follow-up was complete to March 2000.
      Analyses evaluated the rate and timing of all-cause and cardiovascular
      hospitalizations within discrete periods in the five years following the index
      stroke. Cardiovascular hospitalizations included patients with a primary
      diagnosis of ischemic stroke, transient ischemic attack, myocardial infarction,
      stable or unstable angina, heart failure or peripheral arterial disease. RESULTS:
      One-third (36%) of patients were identified by a hospitalized stroke. Mean age
      was 70.5 years, 48.0% were male, half had a history of stroke or a transient
      ischemic attack at the time of their index stroke. Three-quarters of the patients
      (72.7%) were hospitalized at least once during a mean follow-up of 4.6 years,
      accruing CAD $24 million in the first year alone. Of all hospitalizations, 20.4%
      were related to cardiovascular disease and 1.6% to bleeds. In the month following
      index stroke, 12.5% were admitted, an average of 1.04 times per patient
      hospitalized. Strokes accounted for 33% of all hospitalizations in the first
      month. The rate diminished steadily throughout the year and stabilized in the
      second year when approximately one-third of patients required hospitalization, at
      a rate of about one hospitalization for every two patient-years. Mean lengths of
      stay ranged from nine days to nearly 40 days. Close-fitting Weibull functions
      allow highly specific probability estimates. Other cardiovascular risk factors
      significantly increased hospitalization rates. CONCLUSION: After stroke, there
      are frequent hospitalizations accounting for substantial additional costs. Though
      these rates drop after one year, they remain high over time. The number of other
      cardiovascular causes of hospitalization confirms that stroke is a manifestation
      of disseminated atherothrombotic disease.

PMID- 16907985
TI  - Biphasic parapharyngeal synovial sarcoma: a cytologic and immunocytologic report
      of a case.
AB  - BACKGROUND: Synovial sarcoma is a rare soft tissue sarcoma in the head and neck
      region and parapharyngeal space. There is no previous cytologic report of
      synovial sarcoma of parapharynx. The cytologic and immunocytochemical findings of
      a parapharyngeal biphasic synovial sarcoma together with diagnostic pitfalls are
      described. CASE REPORT: A 21-year-old girl presented with a 6-month history of
      progressive right arm pain, neck mass and upper aerodigestive tract obstruction.
      On physical examination there was a large painless mass arising from the right
      sided parapharyngeal space causing airway obstruction. Initial magnetic resonance
      imaging (MRI) revealed a large tumor in the right-sided parapharyngeal space.
      Fine needle aspiration through cervical region was performed and was reported as
      benign spindle cell tumor. Smears were cellular and composed mostly of tight and
      loose clusters of spindle cells. Epitheloid cells could also be identified
      intermingled with them. She underwent near total resection of the tumor.
      Pathologic report disclosed the diagnosis of synovial sarcoma. She then received
      postoperative adjuvant external radiotherapy. CONCLUSION: Due to rarity of this
      tumor in this region and nonspecific cytologic features, we could not
      differentiate this tumor from the other more common spindle cell neoplasms.
      Considering synovial sarcoma in this region and immunocytochemistry can be
      helpful in rendering a correct initial diagnosis of this tumor.

PMID- 16907984
TI  - A rationale and model for addressing tobacco dependence in substance abuse
      treatment.
AB  - Most persons in drug treatment smoke cigarettes. Until drug treatment facilities
      systematically treat their patients' tobacco use, millions will flow through the
      drug treatment system, overcome their primary drug of abuse, but die prematurely
      from tobacco-related illnesses. This paper reviews the literature on the health
      benefits of quitting smoking for drug treatment patients, whether smoking causes
      relapse to other drug or alcohol abuse, the treatment of tobacco dependence, and
      good and bad times for quitting smoking among drug treatment patients. It also
      presents a conceptual model and recommendations for treating tobacco in substance
      abuse treatment, and provides references to internet and paper-copy tools and
      information for treating tobacco dependence. At present, research on tobacco
      treatment in drug treatment is in its infancy. Although few drug treatment
      programs currently offer formal services, many more will likely begin to treat
      nicotine dependence as external forces and patient demand for these services
      increases. In the absence of clear guidelines and attention to quality of care,
      drug treatment programs may adopt smoking cessation services based on cost,
      convenience, or selection criteria other than efficacy. Because research in this
      field is relatively new, substance abuse treatment professionals should adhere to
      the standards of care for the general population, but be prepared to update their
      practices with emerging interventions that have proven to be effective for
      patients in drug treatment.

PMID- 16907986
TI  - Comparison of RCAS1 and metallothionein expression and the presence and activity
      of immune cells in human ovarian and abdominal wall endometriomas.
AB  - BACKGROUND: The coexistence of endometrial and immune cells during
      decidualization is preserved by the ability of endometrial cells to regulate the
      cytotoxic immune activity and their capability to be resistant to immune-mediated
      apoptosis. These phenomena enable the survival of endometrial ectopic cells.
      RCAS1 is responsible for regulation of cytotoxic activity. Metallothionein
      expression seems to protect endometrial cells against apoptosis. The aim of the
      present study was to evaluate RCAS1 and metallothionein expression in human
      ovarian and scar endometriomas in relation to the presence of immune cells and
      their activity. METHODS: Metallothionein, RCAS1, CD25, CD69, CD56, CD16, CD68
      antigen expression was assessed by immunohistochemistry in ovarian and scar
      endometriomas tissue samples which were obtained from 33 patients. The secretory
      endometrium was used as a control group (15 patients). RESULTS: The lowest
      metallothionein expression was revealed in ovarian endometriomas in comparison to
      scar endometriomas and to the control group. RCAS1 expression was at the highest
      level in the secretory endometrium and it was at comparable levels in ovarian and
      scar endometriomas. Similarly, the number of CD56-positive cells was lower in
      scar and ovarian endometriomas than in the secretory endometrium. The highest
      number of macrophages was found in ovarian endometriomas. RCAS1-positive
      macrophages were observed only in ovarian endometriomas. CD25 and CD69 antigen
      expression was higher in scar and ovarian endometriomas than in the control
      group. CONCLUSION: The expression of RCAS1 and metallothionein by endometrial
      cells may favor the persistence of these cells in ectopic localization both in
      scar following cesarean section and in ovarian endometriosis.

PMID- 16907987
TI  - Cell organisation, sulphur metabolism and ion transport-related genes are
      differentially expressed in Paracoccidioides brasiliensis mycelium and yeast
      cells.
AB  - BACKGROUND: Mycelium-to-yeast transition in the human host is essential for
      pathogenicity by the fungus Paracoccidioides brasiliensis and both cell types are
      therefore critical to the establishment of paracoccidioidomycosis (PCM), a
      systemic mycosis endemic to Latin America. The infected population is of about 10
      million individuals, 2% of whom will eventually develop the disease. Previously,
      transcriptome analysis of mycelium and yeast cells resulted in the assembly of
      6,022 sequence groups. Gene expression analysis, using both in silico EST
      subtraction and cDNA microarray, revealed genes that were differential to yeast
      or mycelium, and we discussed those involved in sugar metabolism. To advance our
      understanding of molecular mechanisms of dimorphic transition, we performed an
      extended analysis of gene expression profiles using the methods mentioned above.
      RESULTS: In this work, continuous data mining revealed 66 new differentially
      expressed sequences that were MIPS(Munich Information Center for Protein
      Sequences)-categorised according to the cellular process in which they are
      presumably involved. Two well represented classes were chosen for further
      analysis: (i) control of cell organisation - cell wall, membrane and
      cytoskeleton, whose representatives were hex (encoding for a hexagonal peroxisome
      protein), bgl (encoding for a 1,3-beta-glucosidase) in mycelium cells; and ags
      (an alpha-1,3-glucan synthase), cda (a chitin deacetylase) and vrp (a verprolin)
      in yeast cells; (ii) ion metabolism and transport - two genes putatively
      implicated in ion transport were confirmed to be highly expressed in mycelium
      cells - isc and ktp, respectively an iron-sulphur cluster-like protein and a
      cation transporter; and a putative P-type cation pump (pct) in yeast. Also,
      several enzymes from the cysteine de novo biosynthesis pathway were shown to be
      up regulated in the yeast form, including ATP sulphurylase, APS kinase and also
      PAPS reductase. CONCLUSION: Taken together, these data show that several genes
      involved in cell organisation and ion metabolism/transport are expressed
      differentially along dimorphic transition. Hyper expression in yeast of the
      enzymes of sulphur metabolism reinforced that this metabolic pathway could be
      important for this process. Understanding these changes by functional analysis of
      such genes may lead to a better understanding of the infective process, thus
      providing new targets and strategies to control PCM.

PMID- 16907988
TI  - Serum, urinary, and salivary nitric oxide in rheumatoid arthritis: complexities
      of interpreting nitric oxide measures.
AB  - Nitric oxide (NO) may play important roles in rheumatoid arthritis (RA). RA is an
      inflammatory disease involving joints and other systems including salivary
      glands. To assess NO production in RA patients, we compared levels of serum,
      urine, and salivary nitrite and nitrate (NOx) in patients with RA and normal
      subjects, and we examined the relationships of these measures to disease
      activity. Serum, urine, and NOx levels as well as renal creatinine, NOx clearance
      and fractional excretion rates were compared in 25 RA patients and 20 age- and
      gender-matched healthy controls. Subjects were hospitalized for 3 days and placed
      on a NOx restricted diet. NOx was assayed using nitrate reductase and the Griess
      reagent. RA activity was assessed using standard clinical and laboratory
      measures. While consuming a restricted diet for 3 days to eliminate the effects
      of oral intake of NOx, 24 hour urinary NOx excretion decreased in both RA
      patients and healthy controls. Urine NOx levels at all time points were not
      significantly different between RA patients and normal subjects. Serum NOx levels
      also decreased during the 3 days of NOx restriction, but RA patients had higher
      serum NOx levels at all time points compared with the control group. Likewise,
      serum NOx/creatinine ratios were higher in RA patients than in controls. Although
      basal salivary flow rate and tear flow were lower in RA patients, salivary NOx
      levels did not differ between normal and RA subjects. While renal creatinine
      clearance was not different between the two groups, we found that RA patients had
      lower renal NOx clearance and lower renal NOx fractional excretion. After
      correction of p values for multiple comparisons, there were no significant
      relationships for the RA group between measures of disease activity and the
      urinary NOx, serum NOx, or urinary NOx clearance. Despite interest in the use of
      NO as a marker of disease activity, alterations in renal NOx clearance and
      fractional excretion in RA make it difficult to assess in vivo NO production even
      with strict dietary restriction of NOx intake.

PMID- 16907989
TI  - The structure of IL2 bound to the three chains of the IL2 receptor and how
      signaling occurs.
AB  - The interleukin-2 molecule and receptor were the first of the interleukins to be
      discovered and characterized at the molecular level. Now after 20 years of
      effort, two groups have succeeded in determining the structure of IL2 bound to
      the external domains of the three receptor chains in a quaternary complex. What
      do we know now that we did not know before this structural information was
      available, and how do these new data help us to develop new therapies?

PMID- 16907991
TI  - Primary care consultation, hospital admission, sick leave and disability pension
      owing to neck and low back pain: a 12-year prospective cohort study in a rural
      population.
AB  - BACKGROUND: Neck and low back pain are common musculoskeletal complaints
      generating large societal costs in Western populations. In this study we evaluate
      the magnitude of long-term health outcomes for neck and low back pain, taking
      possible confounders into account. METHOD: A cohort of 2,351 Swedish male farmers
      and rural non-farmers (40-60 years old) was established in 1989. In the first
      survey, conducted in 1990-91, 1,782 men participated. A 12-year follow-up survey
      was made in 2002-03 and 1,405 men participated at both times. After exclusion of
      58 individuals reporting a specific back diagnosis in 1990-91, the study cohort
      encompassed 1,347 men. The health outcomes primary care consultation, hospital
      admission, sick leave and disability pension were assessed in structured
      interviews in 2002-03 (survey 2). Symptoms and potential confounders were
      assessed at survey 1, with the exception of rating of depression and anxiety,
      which was assessed at survey 2. Multiple logistic regression generating odds
      ratios (OR) with 95% confidence intervals (95% CI) was performed to adjust the
      associations between reported symptoms and health outcomes for potential
      confounders (age, farming, workload, education, demand and control at work, body
      mass index, smoking, snuff use, alcohol consumption, psychiatric symptoms and
      specific back diagnoses during follow up). RESULTS: Of the 836 men reporting
      current neck and/or low back pain at survey 1, 21% had had at least one primary
      care consultation for neck or low back problems, 7% had been on sick leave and 4%
      had disability pension owing to the condition during the 12 year follow up.
      Current neck and/or low back pain at survey 1 predicted primary care
      consultations (OR = 4.10, 95% CI 2.24-7.49) and sick leave (OR = 3.22, 95% CI
      1.13-9.22) after potential confounders were considered. Lower education and more
      psychiatric symptoms were independently related to sick leave. Lower education
      and snuff use independently predicted disability pension. CONCLUSION: Few
      individuals with neck or low back pain were on sick leave or were granted a
      disability pension owing to neck or low back problems during 12 years of follow
      up. Symptoms at baseline independently predicted health outcomes. Educational
      level and symptoms of depression/anxiety were important modifiers.

PMID- 16907992
TI  - V-MitoSNP: visualization of human mitochondrial SNPs.
AB  - BACKGROUND: Mitochondrial single nucleotide polymorphisms (mtSNPs) constitute
      important data when trying to shed some light on human diseases and cancers.
      Unfortunately, providing relevant mtSNP genotyping information in mtDNA databases
      in a neatly organized and transparent visual manner still remains a challenge.
      Amongst the many methods reported for SNP genotyping, determining the restriction
      fragment length polymorphisms (RFLPs) is still one of the most convenient and
      cost-saving methods. In this study, we prepared the visualization of the mtDNA
      genome in a way, which integrates the RFLP genotyping information with
      mitochondria related cancers and diseases in a user-friendly, intuitive and
      interactive manner. The inherent problem associated with mtDNA sequences in BLAST
      of the NCBI database was also solved. DESCRIPTION: V-MitoSNP provides complete
      mtSNP information for four different kinds of inputs: (1) color-coded visual
      input by selecting genes of interest on the genome graph, (2) keyword search by
      locus, disease and mtSNP rs# ID, (3) visualized input of nucleotide range by
      clicking the selected region of the mtDNA sequence, and (4) sequences mtBLAST.
      The V-MitoSNP output provides 500 bp (base pairs) flanking sequences for each SNP
      coupled with the RFLP enzyme and the corresponding natural or mismatched primer
      sets. The output format enables users to see the SNP genotype pattern of the RFLP
      by virtual electrophoresis of each mtSNP. The rate of successful design of
      enzymes and primers for RFLPs in all mtSNPs was 99.1%. The RFLP information was
      validated by actual agarose electrophoresis and showed successful results for all
      mtSNPs tested. The mtBLAST function in V-MitoSNP provides the gene information
      within the input sequence rather than providing the complete mitochondrial
      chromosome as in the NCBI BLAST database. All mtSNPs with rs number entries in
      NCBI are integrated in the corresponding SNP in V-MitoSNP. CONCLUSION: V-MitoSNP
      is a web-based software platform that provides a user-friendly and interactive
      interface for mtSNP information, especially with regard to RFLP genotyping.
      Visual input and output coupled with integrated mtSNP information from MITOMAP
      and NCBI make V-MitoSNP an ideal and complete visualization interface for human
      mtSNPs association studies.

PMID- 16907993
TI  - Multinomial logistic regression approach to haplotype association analysis in
      population-based case-control studies.
AB  - BACKGROUND: The genetic association analysis using haplotypes as basic genetic
      units is anticipated to be a powerful strategy towards the discovery of genes
      predisposing human complex diseases. In particular, the increasing availability
      of high-resolution genetic markers such as the single-nucleotide polymorphisms
      (SNPs) has made haplotype-based association analysis an attractive alternative to
      single marker analysis. RESULTS: We consider haplotype association analysis under
      the population-based case-control study design. A multinomial logistic model is
      proposed for haplotype analysis with unphased genotype data, which can be
      decomposed into a prospective logistic model for disease risk as well as a model
      for the haplotype-pair distribution in the control population. Environmental
      factors can be readily incorporated and hence the haplotype-environment
      interaction can be assessed in the proposed model. The maximum likelihood
      estimation with unphased genotype data can be conveniently implemented in the
      proposed model by applying the EM algorithm to a prospective multinomial logistic
      regression model and ignoring the case-control design. We apply the proposed
      method to the hypertriglyceridemia study and identifies 3 haplotypes in the
      apolipoprotein A5 gene that are associated with increased risk for
      hypertriglyceridemia. A haplotype-age interaction effect is also identified.
      Simulation studies show that the proposed estimator has satisfactory finite
      sample performances. CONCLUSION: Our results suggest that the proposed method can
      serve as a useful alternative to existing methods and a reliable tool for the
      case-control haplotype-based association analysis.

PMID- 16907994
TI  - Annual prevalence of diagnosed schizophrenia in the USA: a claims data analysis
      approach.
AB  - BACKGROUND: Schizophrenia is a debilitating chronic mental illness. However, the
      annual prevalence of schizophrenia is not well understood because of under
      representation of schizophrenia patients in epidemiological surveys. This study
      used multiple administrative claims databases to estimate the annual prevalence
      of diagnosed schizophrenia in the USA. METHOD: The annual prevalence of diagnosed
      schizophrenia in the USA was estimated for different health insurance coverage
      groups. The prevalence for privately insured individuals was calculated from an
      administrative claims database of approximately 3 million privately insured
      beneficiaries covering the period 1999-2003. The prevalence for Medicaid
      enrollees was calculated from California Medicaid claims covering the period 2000
      2002. The prevalence for Medicare and Medicaid/Medicare dual eligibles was
      estimated using a combination of both databases. Published statistics were used
      to estimate the prevalence of schizophrenia in the uninsured and veteran
      populations and to weight the prevalence rates obtained to the population of the
      USA. RESULTS: The 12-month prevalence of diagnosed schizophrenia in the USA in
      2002 was estimated at 5.1 per 1000 lives. The Medicaid population was identified
      with the highest prevalence rate among the populations studied. Sensitivity
      analyses taking into consideration the Veterans Affairs population only changed
      the estimate slightly to 5.3 per 1000 lives. CONCLUSION: Analyses of
      administrative claims data contribute to the understanding of the prevalence of
      diagnosed schizophrenia.

PMID- 16907995
TI  - The feasibility and need for dimensional psychiatric diagnoses.
AB  - BACKGROUND: It is our contention that both categorical and dimensional approaches
      to diagnosis are important for clinical work and research alike, and that each
      approach has its drawbacks and advantages. As the processes toward developing DSM
      V and ICD-11 progress, we suggest that another exclusively categorical revision
      of psychiatric taxonomies will no longer be sufficient and that adding a
      dimensional component is a necessary step if these taxonomies are to continue
      serving the future clinical and research needs of psychiatry as they have so
      effectively done in the past. METHOD: We begin the paper with a review of
      terminology related to categories and dimensions and briefly review literature on
      advantages and disadvantages of both approaches. RESULTS: A review of relevant
      literature supports both the need for and feasibility of augmenting traditional
      categorical diagnoses with dimensional information. CONCLUSION: We conclude with
      a proposal for preserving traditional categorical diagnostic definitions, but
      adding a dimensional component that would be reflective of and directly referable
      back to the categorical definitions. We also offer a specific proposal for adding
      a dimensional component to official taxonomies such as the DSM and the ICD in a
      way that fully preserves the traditional categorical approach.

PMID- 16907996
TI  - Burrowing behaviour affects Paraergasilus rylovi abundance in Anodonta
      piscinalis.
AB  - Burrowing depth may affect predation rate, feeding ability and reproduction in
      bivalve clams. We studied the effect of burrowing depth on the abundance of the
      ergasilid Paraergasilus rylovi in the freshwater bivalve clam Anodonta
      piscinalis. We transplanted uninfected clams to a lake where they were allowed to
      choose their preferred burrowing depth, and were exposed naturally to copepodids
      of the parasite. There was a significant positive correlation between
      proportionate burrowing depth (PBD) and the abundance of P. rylovi at the end of
      the 17-day experiment, the deeper-burrowed clams harbouring more P. rylovi.
      Original PBD (0%, 50%, 100%) did not influence the final PBD or parasite
      abundance. Clam length affected PBD, smaller clams burrowing deeper, but it did
      not affect parasite abundance. Infected experimental clams and naturally-burrowed
      uninfected clams, both originating from the same lake, did not differ in their
      mean PBD. This indicated that burrowing of the experimental clams affected
      parasitism rather than the parasites altering burrowing of the clams. In line
      with the experimental result, we observed a significant positive correlation
      between PBD and the abundance of P. rylovi also among clams collected from 2
      natural A. piscinalis populations.

PMID- 16907997
TI  - Selecting patients for osteoporosis therapy.
AB  - There is a global need to identify individuals at risk for osteoporotic fracture
      so that those at high risk can be treated and unnecessary treatment for those at
      low risk can be avoided. Bone mineral density (BMD) information is not sufficient
      to identify patients at high risk; approximately half of patients in the
      community with fractures do not have osteoporosis by the 1994 World Health
      Organization BMD criteria. Furthermore, BMD information is not easily accessible
      worldwide. The use of clinical risk factors with or without BMD information will
      improve our ability to identify patients at high risk for fracture. These risk
      factors can be integrated to predict a 10-year absolute risk or probability of
      fracture. Intervention thresholds based on absolute risk will be defined
      regionally based on each nation's ability and willingness to pay.

PMID- 16907998
TI  - The role of vitamin D for bone health and fracture prevention.
AB  - Vitamin D inadequacy is pandemic in adults. Vitamin D deficiency causes
      osteopenia, precipitates and exacerbates osteoporosis, causes the painful bone
      disease osteomalacia, and increases muscle weakness, which worsens the risk of
      falls and fractures. Vitamin D deficiency can be prevented by sensible sun
      exposure and adequate supplementation. Monitoring serum 25-hydroxyvitamin D is
      the only way to determine vitamin D status. Recent recommendations suggest that
      in the absence of sun exposure, adults should ingest 1000 IU of vitamin D3 per
      day. The ideal healthy blood level of 25-hydroxyvitamin D should be 30 to 60
      ng/mL. Vitamin D intoxication occurs when 25-hydroxyvitamin D levels are greater
      than 150 ng/mL. Three recent reports suggesting that vitamin D and calcium
      supplementation does not decrease the risk of fracture will be put into
      perspective in light of the vast literature supporting increasing vitamin D and
      calcium intake as an effective method for decreasing risk of vertebral and
      nonvertebral fractures.

PMID- 16907999
TI  - Stress fractures: pathophysiology, epidemiology, and risk factors.
AB  - A stress fracture represents the inability of the skeleton to withstand
      repetitive bouts of mechanical loading, which results in structural fatigue and
      resultant signs and symptoms of localized pain and tenderness. To prevent stress
      fractures, an appreciation of their risk factors is required. These are typically
      grouped into extrinsic and intrinsic risk factors. Extrinsic risk factors for
      stress fractures are those in the environment or external to the individual,
      including the type of activity and factors involving training, equipment, and the
      environment. Intrinsic risk factors for stress fractures refer to characteristics
      within the individual, including skeletal, muscle, joint, and biomechanical
      factors, as well as physical fitness and gender. This article discusses these
      extrinsic and intrinsic risk factors, as well as the pathophysiology and
      epidemiology of stress fractures.

PMID- 16908000
TI  - Epidemiology and pathophysiology of osteoporosis in men.
AB  - Osteoporosis in men is an unrecognized but growing problem as the number of men
      who live to old age increases. The 10-year fracture risk at age 50 quadruples by
      age 80, and in general the incidence rate of osteoporotic fracture in men is
      about half that of women. Of note, the mortality and morbidity after hip fracture
      are much greater in men. There are many men whose osteoporosis is the result of
      specific causes such as oral glucocorticoid therapy, hypogonadism, or androgen
      withdrawal therapy for prostate cancer. In addition there are several interesting
      syndromes of osteoporosis in middle-aged men; these men usually present with
      vertebral fractures. As knowledge about the prevalence and etiology of
      osteoporosis in men increases, it will be recognized and treated in more men, in
      hopes of preventing fracture.

PMID- 16908001
TI  - Inflammatory bowel diseases as secondary causes of osteoporosis.
AB  - Inflammatory bowel disease (IBD), comprising Crohn's disease and ulcerative
      colitis, is associated with an increased risk of osteoporosis and bone fractures.
      Initial studies suggested very high rates of osteoporosis in IBD, but more recent
      studies have suggested that bone mineral density (BMD) is often normal in
      patients with IBD and typically changes little over time. Nonetheless, IBD is
      associated with an increased risk of fractures. Doctors managing patients with
      IBD must consider a variety of risk factors, not just BMD measurements, in
      assessing fracture risk. Advances have been made in exploring the pathogenesis of
      osteoporosis in IBD. The evolution of knowledge regarding receptor for activated
      factor of nuclear factor kappaB (RANK), its ligand RANKL, and osteoprotegerin
      (OPG), which serves as a decoy receptor, has enhanced the understanding of both
      osteoporosis and T-cell immunobiology. Recent clinical studies in patients with
      IBD have revealed that serum OPG levels may be elevated and inflamed intestinal
      tissue secretes increased amounts of OPG. It is suspected that OPG levels are
      elevated as a counterregulatory response to low BMD, as serum OPG levels in IBD
      have been found to be inversely associated with BMD. Finally, in animal models of
      IBD, exogenous OPG has reversed both the osteopenia and the enterocolitis,
      suggesting that it may have a therapeutic role in human IBD.

PMID- 16908002
TI  - Perceived physical and social causality in animated motions: spontaneous reports
      and ratings.
AB  - Michotte argued that we perceive cause-and-effect, without contributions from
      reasoning or learning, even in displays of two-dimensional moving shapes. Two
      studies extend this line of work from perception of mechanical to social
      causality. We compared verbal reports with structured ratings of causality to
      gain a better understanding of the extent to which perceptual causality occurs
      spontaneously or depends on instruction or context. A total of 120 adult
      observers (72 in the main experiment, 48 in an initial experiment) saw 12 (or 8)
      different computer animations of shape A moving up to B, which in turn moved
      away. Animations factorially varied the temporal and spatial relations of the
      shapes, and whether they moved rigidly or in a non-rigid, animal-like manner.
      Impressions of social as well as physical causality appeared in both free reports
      and ratings. Perception of physical causality was stronger than perception of
      social causality, particularly in free reports. No differences of this nature
      appear in infants and children, so the asymmetry may reflect learnt knowledge.
      Physical causality was relatively unspecific initially, but discrimination of
      causal and delayed control events improved with exposure to multiple events.
      Experience seems to affect the causal illusion even over a short timeframe; the
      idea of 'one-trial causality' may be somewhat misleading. Regardless of such
      effects on the absolute level of responses, the different measures showed similar
      patterns of variation with the spatio-temporal configuration and type of motion.
      The good fit of ratings and reports validates much recent work in this area.

PMID- 16908003
TI  - Toward the detection of single virus particle in serum.
AB  - There is a grand challenge for the detection of target molecules at single
      molecule sensitivity in a bulk body fluid for the early diagnosis of diseases. We
      report our progress on tackling this challenge via the combination of
      fluorescence cross-correlation spectroscopy (FCCS) and micro fabricated devices
      toward highly sensitive detection of the dengue virus. We demonstrate that by
      using a dengue-specific antibody, we can probe the individual dengue virus in a
      nanomolar bulk solution by following the specific association of dengue antibody
      using FCCS. Consequently, we designed and fabricated a microfluidic chamber array
      structure and were able to compartmentalize the bulk aqueous dengue sample into
      femtoliter volumes using such a device. More importantly we demonstrate that we
      can differentiate between the compartments containing the dengue virus and the
      virus-free compartments. Our experiment suggests that by expanding the throughput
      using microfluidic devices integrated with FCCS, both of which can be achieved
      practically, we should be able to detect single virus particle in human body
      fluids in the near future.

PMID- 16908004
TI  - Identification of the size and antigenic determinants of the human C4 gene by a
      polymerase chain-reaction-based amplification method.
AB  - The human C4 complement components of the C4 locus are encoded by two genes, C4A
      and C4B, located on chromosome 6p21.3 of the major histocompatibility complex of
      the human leukocyte antigen class III region. The size difference between the two
      genes is due to the presence of HERV-K (C4), an endogenous retroviral sequence
      (6.7 kb long), in intron 9 of the long C4 gene. Whether the C4 is the long (L) or
      short (S) gene was determined by the Southern blot method, and the antigenic
      determinants in residues 1,054-1,106 of Rodgers and Chido were generally
      identified by immunoblot analysis. Herein, we explore a polymerase chain reaction
      (PCR) amplification method for directly determining the size of C4 loci adjacent
      to the respective RP1 and RP2 genes and antigenic determinants by DNA sequencing.
      From the results of this study, we concluded that all of the C4 genes adjacent to
      the RP1 gene presented the long gene. In addition, 47% of the C4 genes adjacent
      to the RP2 gene were the short gene and 53% were the long gene. This result was
      consistent with that of the Southern blot analysis. The PCR method is practical
      for identifying the C4 genotype and can be used to detect other polymorphisms
      among variants of C4 genes.

PMID- 16908005
TI  - The effect of mediation on impression formation: a comparison of face-to-face and
      video-mediated conditions.
AB  - It is suggested that communication mediated by video may have an important impact
      on the way in which individuals are perceived and this might be a result of an
      attenuation or distortion of visual signals. The current study aimed to test this
      further by employing a simple mind-reading task, which gave participants an
      opportunity to interact with one another. Participants completed the task in
      pairs either face-to-face or via video-mediated technologies. After completing
      the task, participants filled in a questionnaire which was designed to assess
      perceptions of how much they liked and how intelligent they believed their
      partner in the task to be. Results indicate that participants were regarded as
      significantly less likeable and intelligent in the video-mediated condition. This
      is probably a consequence of the attenuation of visual signals, in particular eye
      gaze, which has been shown to be important in impression formation. Findings from
      this study have practical implications for using this type of technology to
      assess performance, for example in interviews, especially if comparisons are made
      with face-to-face interviewees.

PMID- 16908006
TI  - Design and feasibility study of an integrated pointing device apparatus for
      individuals with spinal cord injury.
AB  - Despite the commercial availability of numerous computer-pointing devices, many
      severely disabled individuals still rely on customized equipment to operate
      computers. This study presents a novel Integrated Pointing Device Apparatus
      (IPDA) that integrates numerous commercial pointing devices. The novel IPDA,
      which complies with a standard USB 1.1 interface, is compatible with most tested
      computer-pointing devices and flexibly integrates commercial computer devices,
      tailoring them to suit individual needs. By using simple integrated circuit
      design and low-cost electronic components, this low-cost apparatus is easily
      maintained. The feasibility of the IPDA was evaluated by four subjects with high
      level cervical (C4-5) spinal cord injury (SCI). Participants performed normal
      move-and-click and drag-and-drop tasks typically performed by computer pointing
      devices. Each participant not able to use a traditional computer mouse or
      trackball were able to operate a computer adequately with the IPDA and three
      including one operating a trackball with his chin, operated computers easily and
      smoothly. This feasibility study showed that the IPDA effectively integrates
      commercial pointing devices, thereby providing the possibility for some people
      with SCI to obtain computer operability. This study demonstrated the advantages
      of flexibility, low cost, and acceptable efficiency of the novel IPDA.

PMID- 16908007
TI  - Alpha-tocopherol induces calnexin in renal tubular cells: another protective
      mechanism against free radical-induced cellular damage.
AB  - Pre-administration of alpha-tocopherol is protective against oxidative renal
      tubular damage and subsequent carcinogenesis by ferric nitrilotriacetate (Fe-NTA)
      in rats. We searched for mechanisms other than the scavenging effect of alpha
      tocopherol with microarray analyses, which implicated calnexin, a chaperone for
      glycoproteins. Renal mRNA levels of calnexin significantly increased 3h after an
      injection of Fe-NTA in rats fed a standard diet whereas those fed an alpha
      tocopherol-supplemented diet showed an increase prior to injection, but after
      injection showed a decrease in renal calnexin mRNA levels, with unaltered protein
      levels. In experiments using LLC-PK1 cells, addition of alpha-tocopherol was
      protective against oxidative stress by H2O2, concomitant with calnexin induction.
      Knockdown of calnexin by siRNA significantly reduced this protection.
      Furthermore, COS-7 cells transfected with the calnexin gene were more resistant
      to H2O2. Together with the fact that alpha-tocopherol induced N
      acetylglucosaminyltransferase 3, our data suggest that alpha-tocopherol modifies
      glycoprotein metabolism partially by conferring mild ER stress. This adds another
      molecular mechanism of alpha-tocopherol toward cancer prevention.

PMID- 16908009
TI  - Membrane interaction and activity of the glycolipid transfer protein.
AB  - In this study we have addressed the ability of the glycolipid transfer protein
      (GLTP) to transfer anthrylvinyl-galactosylceramide at different pH and sodium
      chloride concentrations, and the ability of three different mutants to transfer
      the fluorescently labeled galactosylceramide between donor and acceptor model
      membranes. We constructed single tryptophan mutants with site-directed
      mutagenesis where two of the three tryptophan (W) of wild-type human GLTP were
      substituted with phenylalanine (F) and named W85 GLTP (W96F and W142F), W96 GLTP
      (W85F and W142F) and W142 GLTP (W85F and W96F) accordingly. Wild-type GLTP and
      W96 GLTP were both able to transfer anthrylvinyl-galactosylceramide, but the two
      variants W85 GLTP and W142 GLTP did not show any glycolipid transfer activity,
      indicating that the tryptophan in position 96 is crucial for transfer activity.
      Tryptophan fluorescence emission showed a blue shift of the maximal emission
      wavelength upon interaction of glycolipid containing vesicle with wild-type GLTP
      and W96 GLTP, while no blue shift was recorded for the protein variants W85 GLTP
      and W142 GLTP. The quantum yield of tryptophan emission was highest for the W96
      GLTP protein whereas W85 GLTP, W142 GLTP and wild-type GLTP showed a lower and
      almost similar quantum yield. The lifetime and anisotropy decay of the different
      tryptophan mutants also changed upon binding to vesicles containing
      galactosylceramide. Again wild-type GLTP and W96 GLTP showed similar behavior in
      the presence of vesicles containing glycolipids. Taken together, our data show
      that the W96 is involved not only in the activity of the protein but also in the
      interaction between the protein and glycolipid containing membranes.

PMID- 16908008
TI  - The menaquinol-oxidizing cytochrome bc complex from Thermus thermophilus: protein
      domains and subunits.
AB  - A recently resolved respiratory complex III, isolated from the extreme
      thermophile Thermus thermophilus, is discussed in terms of cofactor and subunit
      composition, and with respect to the origin of its protein modules. The four
      polypeptides, encoded by a single operon, share general homologies to canonical
      complexes both of the bc and b6f type, but exhibit some unexpected features as
      well. Evidence for high thermostability of the isolated protein and for its
      quinol substrate specificity is derived from EPR and kinetic measurements. A
      functional integration of this complex into an aerobic electron transfer scheme,
      connecting known dehydrogenase activities to the terminal oxidase branches of
      Thermus is outlined, as well as the specific principles of redox protein
      interactions prevailing at high temperature. Findings from this enzyme are linked
      to present knowledge on other menaquinol oxidizing bc complexes.

PMID- 16908010
TI  - Reconstitution of the NF1 GAP-related domain in NF1-deficient human Schwann
      cells.
AB  - Schwann cells derived from peripheral nerve sheath tumors from individuals with
      Neurofibromatosis Type 1 (NF1) are deficient for the protein neurofibromin, which
      contains a GAP-related domain (NF1-GRD). Neurofibromin-deficient Schwann cells
      have increased Ras activation, increased proliferation in response to certain
      growth stimuli, increased angiogenic potential, and altered cell morphology. This
      study examined whether expression of functional NF1-GRD can reverse the
      transformed phenotype of neurofibromin-deficient Schwann cells from both benign
      and malignant peripheral nerve sheath tumors. We reconstituted the NF1-GRD using
      retroviral transduction and examined the effects on cell morphology, growth
      potential, and angiogenic potential. NF1-GRD reconstitution resulted in
      morphologic changes, a 16-33% reduction in Ras activation, and a 53% decrease in
      proliferation in neurofibromin-deficient Schwann cells. However, NF1-GRD
      reconstitution was not sufficient to decrease the in vitro angiogenic potential
      of the cells. This study demonstrates that reconstitution of the NF1-GRD can at
      least partially reverse the transformation of human NF1 tumor-derived Schwann
      cells.

PMID- 16908011
TI  - A targeted proteomic approach for the identification of tumor-associated membrane
      antigens using the ProteomeLab PF-2D in tandem with mass spectrometry.
AB  - Mapping differential expression of soluble proteins has become fairly routine
      using chromatofocusing in combination with the reversed-phase HPLC (ProteomeLab
      PF-2D by Beckman Coulter Inc.); however, identification of membrane antigens has
      not been reported thus far. In this report, we demonstrate a targeted proteomic
      approach employing immunoprecipitation, prior to 2D-LC separation, in tandem with
      MS/MS that can be used to identify tumor-associated membrane antigens. This
      system is very sensitive and reproducible in that only 1/4th the amount of
      starting material is required for analysis as compared to gel-based analysis, and
      permits a focused environment for eliminating non-specific interactions leading
      to an accurate resolution of the cognate antigen. This system also circumvents
      the well-known limitations associated with gel-based approaches. This approach
      has been validated in the identification of ErB2/HER-2 and was subsequently used
      to identify CD44E as the cognate antigen for VB1-008, one of our fully human,
      tumor-specific, monoclonal antibodies.

PMID- 16908012
TI  - Quantitative evaluation of monocyte transmigration into the brain following
      chemical opening of the blood-brain barrier in mice.
AB  - The blood-brain barrier (BBB) is a major obstacle to gene therapy for genetic and
      infectious diseases in the central nervous system (CNS). At present, invasive
      techniques such as direct intracerebral injection of viral vector are necessary
      for clinical applications. Our laboratory is interested in developing a
      noninvasive cell-based gene delivery system for the CNS that exploits the natural
      ability of monocytes to enter the brain. With this in mind, fluorescently labeled
      monocytes were inoculated into the carotid artery of live mice, and their ability
      to enter the CNS was quantified by microscopic analysis of brain tissue sections
      obtained at necropsy. Labeled monocytes were detected in hippocampus, thalamus
      and cortex of experimental mice, and cell migration was confirmed by
      immunohistochemical analysis of tissue sections using a monocyte/macrophage
      specific monoclonal antibody. Cell entry into the CNS could be enhanced by prior
      treatment of mice with intravenous bradykinin or hypertonic mannitol, with
      optimum results being obtained when bradykinin (5 mg/kg) or hypertonic mannitol
      was delivered 20 min prior to infusion of monocytes. These results suggest that
      it may be possible to transiently manipulate BBB permeability in such a way to
      achieve efficient migration of monocytes in the brain. This opens the way for the
      future use of vector-transduced monocytes as a novel delivery system to achieve
      effective gene transfer into the CNS.

PMID- 16908013
TI  - Readily available porcine aortic valve matrices for use in tissue valve
      engineering. Is cryopreservation an option?
AB  - The clinical use of acellular biological valves as scaffolds in tissue valve
      engineering would require them to be readily available. This study examines the
      feasibility of cryopreserving porcine aortic valve matrices for use in tissue
      valve engineering. Matrices prepared using an enzymatic-detergent
      decellularization protocol were examined before and after cryopreservation. The
      biochemical status of tissues were evaluated by collagen and uronic acid
      (proteoglycan) determination and their mechanical properties were determined
      using a burst test. The histological and ultrastructural properties were
      evaluated by light and electron microscopy. Cryopreservation did not
      significantly affect the collagen and uronic acid content of aortic leaflet
      matrices. Histological and ultrastructural sections, however, confirmed extensive
      disruption of the extracellular collagen matrix and inter-fibrillar proteoglycan
      associations following cryopreservation. Although neither the breakage force nor
      the maximum force at failure was significantly different in matrices before and
      after cryopreservation, the strain observed in matrices was significantly higher
      after cryopreservation. To our knowledge this is the first study to investigate
      the effects of cryopreservation on aortic valve matrices. Cryopreservation did
      not significantly alter the biochemical properties of porcine aortic valve
      matrices. Nevertheless, cryopreservation had significant adverse effects on the
      structural and mechanical properties of matrices. Cryopreserved matrices showed
      significantly higher strain when stressed compared to non cryopreserved matrices.
      While, theoretically matrices are only expected to be functional for a limited
      time until regenerated in vivo, further mechanical testing is necessary to
      evaluate the effects of these changes on the durability of porcine aortic valve
      matrices for use in tissue valve engineering.

PMID- 16908014
TI  - The preantral granulosa cell to cumulus cell transition in the mouse ovary:
      development of competence to undergo expansion.
AB  - The transition of preantral to antral follicles is one of the major steps in
      follicular development, yet little is known about the molecular and functional
      changes that occur as preantral granulosa cells differentiate into cumulus cells.
      The cumulus oophorus of large antral follicles undergoes expansion in response to
      the preovulatory surge of gonadotropins, but preantral granulosa cells do not.
      The objective of this project was to determine the molecular mechanisms
      underlying this differential response. Cumulus expansion in vitro requires
      secretion of cumulus-expansion enabling factors (CEEFs) by the oocyte and
      stimulation by a ligand, epidermal growth factor (EGF) or follicle-stimulating
      hormone (FSH). This combined stimulation results in activation of MAPKs (MAPK3/1
      (formerly ERK1/2) and MAPK14 (formerly p38)) and increased Has2, Ptgs2, Tnfaip6
      and Ptx3 mRNA levels, all of which are required for cumulus expansion. Only fully
      grown oocytes from antral follicles were competent to enable expansion and
      increases in expansion-related transcripts in cumulus cells, whereas growing
      oocytes of preantral follicles did not. To assess the competence of preantral
      granulosa cells to generate responses associated with expansion, they were
      treated with FSH or EGF and co-cultured with fully-grown oocytes secreting CEEFs.
      MAPKs were activated by EGF in preantral granulosa cells to essentially the same
      levels as in cumulus cells. Preantral granulosa cells treated with EGF, but not
      those treated with FSH increased Has2, Ptgs2 and Ptx3 mRNAs to 17-96% of the
      levels observed in cumulus cells. In contrast, the level of Tnfaip6 mRNA was
      minimally stimulated in preantral granulosa cells. Therefore, preantral granulosa
      cells do not undergo expansion for two fundamental reasons. First, the growing
      oocytes of preantral follicles do not secrete active CEEFs. Second, activation of
      MAPKs alone in preantral granulosa cells, even in the presence of CEEFs, is not
      sufficient to increase the expression of essential transcripts, particularly
      Tnfaip6 mRNA. Thus, preantral granulosa cells differ from cumulus cells in CEEF
      dependent processes downstream of the activation of MAPKs.

PMID- 16908015
TI  - Stage-specific Importin13 activity influences meiosis of germ cells in the mouse.
AB  - Importin-mediated transport of cargoes is known to be a key mechanism for nucleo
      cytoplasmic trafficking of molecules. Ipo13, which is a member of Importin-beta
      gene family, encodes two transcripts by utilizing different transcription start
      sites. In the mouse, the full-length transcript (L-Ipo13) is expressed in the
      primordial germ cells in the embryo and is later expressed predominantly at the
      pachytene phase of meiosis in both male and female germ cells. The shorter
      transcript (TS-Ipo13) is only expressed in the germ cells in the adult testis.
      Activity of L-Ipo13, but not TS-Ipo13, mediates the nuclear accumulation of
      ubiquitin-conjugating enzyme 9 (UBC9), a cargo of human IPO13. This finding is
      consistent with the progressive accumulation of UBC9 in the nucleus of the
      meiotic germ cells after the onset of L-Ipo13 expression. Following siRNA
      knockdown of IPO13 activity in the fetal ovary, fewer germ cells are found to
      progress to the late-pachytene stage of meiosis and nuclear accumulation of UBC9
      is reduced. Our findings strongly implicate a stage-specific role of IPO13 in
      nuclear-cytoplasmic translocation of cargoes that accompanies meiotic
      differentiation of the mouse germ cells.

PMID- 16908016
TI  - Estimating dietary consumption patterns among children: a comparison between
      cross-sectional and longitudinal study designs.
AB  - Estimating dietary intake for children is an essential component of conducting
      pesticide exposure assessments given the fact that children are predominantly
      exposed to certain pesticides, such as organophosphorus pesticide, through
      dietary intake. Different study designs and their respective sampling methodology
      utilized to estimate food consumption patterns can significantly alter the
      parameter estimates and the variability in the values obtained. This study
      investigated the impacts of study design on overall estimates of dietary intake
      by applying the temporal sampling characteristics used in cross-sectional
      approaches, as in The Continuing Survey of Food for Intakes by Individuals
      (CSFII), to food consumption data collected in a longitudinal manner via a
      bootstrap sampling technique. We examined the precision of time-averaged dietary
      intake estimates under various sampling schemes and explored the contribution of
      seasonality toward the dietary patterns. A comparison between the estimates of
      food consumption obtained from the bootstrap replicates and the longitudinal
      study estimates indicate that variability is significantly decreased when
      employing a longitudinal study design. Moreover, both between and within-subject
      variability decreases when individuals are followed over an increasing number of
      days. Finally, within the longitudinal study cohort, we observed a seasonal
      component to dietary intake for fruits and grains. Our findings suggest that
      longitudinal dietary surveys offer substantial improvements for exposure
      assessment compared to a standard cross-sectional design.

PMID- 16908017
TI  - Modulation by homocysteine of the iberiotoxin-sensitive, Ca2+ -activated K+
      channels of porcine coronary artery smooth muscle cells.
AB  - We evaluated the acute effect of homocysteine on the iberiotoxin-sensitive,
      Ca(2+)-activated K(+) (BK(Ca)) channels of the porcine coronary artery smooth
      muscle cells. NS 1619 (1 to 30 microM) caused a concentration-dependent
      enhancement of the BK(Ca) amplitude (recorded using the whole-cell, membrane
      rupture configuration) only with an elevated [Ca(2+)](i) of approximately 444 nM,
      but not with [Ca(2+)](i) of approximately 100 nM. Homocysteine (30 microM) caused
      a small inhibition ( approximately 16%) of the BK(Ca) amplitude ([Ca(2+)](i)=
      approximately 444 nM), and a greater inhibition ( approximately 77%) was observed
      with 100 microM NADH present in the pipette solution. The inhibition persisted
      after washing. With NADPH (100 microM), a smaller magnitude of inhibition (
      approximately 34%) of the BK(Ca) amplitude was recorded. The NS 1619-mediated
      enhancement of the BK(Ca) amplitude (with elevated [Ca(2+)](i) plus NADH in the
      pipette) was attenuated by homocysteine. The homocysteine-mediated inhibition of
      the BK(Ca) amplitude was suppressed by Tiron (10 mM) or diphenylene iodonium (30
      nM), applied alone, but not by superoxide dismutase (500 U/ml) and catalase (500
      U/ml). Generation of superoxide (O(2)(-)) of the smooth muscle cells (with NADH
      presence), measured using the lucigenin-enhanced chemiluminescence, was markedly
      increased by angiotensin II (100 nM) and homocysteine (30 microM). The
      chemiluminescence signal was sensitive to apocynin (300 microM) or Tiron, applied
      alone, but not to superoxide dismutase and catalase. In conclusion, our results
      demonstrate that acute homocysteine application inhibits the iberiotoxin
      sensitive BK(Ca) channels (with elevated [Ca(2+)](i) and NADH present) which is
      probably caused by the NADH oxidase activation and the concomitant generation of
      intracellular superoxide.

PMID- 16908018
TI  - The immunophenotype of pre-TALL/LBL revisited.
AB  - Flow cytometric analysis of cluster of differentiation (CD) markers in abnormal
      lymphocyte populations is crucial in the diagnosis of precursor T cell acute
      lymphoblastic leukemia (T-ALL)/lymphoblastic lymphoma (LBL). The World Health
      Organization (WHO) suggested immunophenotype for pre-T ALL/LBL typically includes
      the expression of TdT, cCD3, and CD7, while CD2, CD3, CD4, CD5, CD8, and CD10 are
      variably expressed. The myeloid antigens CD13 and CD33 are usually positive,
      whereas CD117 and cCD79a are infrequently expressed. Furthermore, there is
      frequent dual expression of CD4 and CD8. In the present investigation, 19 cases
      of pre-TALL/LBL were analyzed for selected CD marker expression. Fifteen of 19
      cases studied were evaluated for TdT, cCD3, and cCD79a expression. Eleven (73.3%)
      positively expressed TdT, 15 (100%) positively expressed cCD3, and 9 (60%)
      positively expressed cCD79a. Of the 17 cases analyzed for CD7, CD5, and CD10
      expression, CD7 and CD5 were positive in all 17 (100%) cases, whereas CD10 was
      positive in 8 (47.1%) cases. Of the 18 cases evaluated for CD2, CD3, CD4, CD8,
      and dual expression of CD4 and CD8, CD2 was expressed in 14 (77.8%), while CD3
      was expressed in 7 (38.9%) cases. CD4 was positive in 11 (61.1%), and CD8 was
      expressed in 9 (50%). Dual expression of CD4 and CD8 occurred in only 4 (22.2%)
      of the cases. Of the 16 analyzed for CD13, CD33, and CD117, only 1 case (6.3%)
      expressed CD13, while 2 (12.5%) cases expressed CD33 and CD117. Thus, these data
      point to the need for a more extensive study to reevaluate the current WHO
      defined immunophenotype used in the diagnosis of pre-TALL/LBL.

PMID- 16908019
TI  - Antigenic transformation in plasma cell dyscrasia.
AB  - The WHO immunophenotype for plasma cell myeloma is deletion of CD19 and CD20,
      usual expression of CD38, CD138, and CD56, and occasional expression of CD10. Of
      the 39 cases of plasma cell dyscrasia in our study, the mean fluorescence
      intensities (MFI) of CD38, CD138, CD56, and CD19 were quantified in 30 cases.
      CD19 was absent in 38 of the cases (97.4%), whereas CD138 and CD38 were expressed
      in all 39 cases (100%). Most cases expressed CD38 and CD138 brightly with MFI
      values greater than 501, whereas all other marker expression was moderate with
      MFI greater than 301. Whereas CD38/CD56 dual expression was observed in 25 cases
      (64.1%), 14 failed to express CD56 (35.9%). CD56 expression was bright in 16
      cases (53.3%), moderate in 2 cases (6.7%), and negative in the remaining 12 cases
      (40%) with MFI values of 200 or less. CD117 expression was positive in 9 of 24
      cases (37.5%). In 32 of 39 cases, 27 were negative for CD20 (84.4%) and 28 were
      negative for CD10 (87.5%). Our results point to the value of quantitative
      fluorescence intensity in the flow cytometric evaluation of CD molecular
      expression or deletion in the diagnosis of hematopathologic disorders, such as
      plasma cell dyscrasia.

PMID- 16908020
TI  - Changes in sodium channel expression following trigeminal nerve injury.
AB  - We have investigated the expression of TTX-sensitive (TTXs) and TTX-resistant
      (TTXr) sodium channel subtypes following injury to the inferior alveolar nerve
      (IAN), in order to determine their potential role in the development of
      trigeminal neuropathic pain. In seven anaesthetised ferrets, fluorogold (2%) was
      injected into the left IAN to identify cell bodies with axons in this nerve. In
      four animals, the nerve was sectioned distal to the injection site and the
      remaining three served as controls. After 3 days, the animals were perfused with
      4% paraformaldehyde. The left and right IANs and trigeminal ganglia were
      processed using indirect immunofluorescence with specific primary antibodies to
      TTXs subtypes Na(v)1.3 and Na(v)1.7 and TTXr subtypes Na(v)1.8 and Na(v)1.9.
      Image analysis was used to quantify the percentage area of staining (PAS) in the
      nerves. In the ganglia, counts were made of positively labelled cells in the
      fluorogold population. PAS for Na(v)1.8 and Na(v)1.9 was significantly greater in
      injured nerves than in either contralateral or control nerves. After injury,
      significantly fewer cells in the ganglia expressed Na(v)1.3 (controls 36.9%;
      injured 13.1%), Na(v)1.7 (controls 17.0%; injured 8.1%) and Na(v)1.9 (controls
      60.3%; injured 29.0%) (p<0.05, unpaired t test). These changes are different from
      those previously reported in the dorsal root ganglion following damage to
      peripheral nerves of spinal origin. As they occur at a time of known high
      abnormal neural discharge, it seems likely that changes in sodium channel
      expression may play a role in nerve injury-induced trigeminal pain.

PMID- 16908021
TI  - The risk is in the air: Intranasal administration of MPTP to rats reproducing
      clinical features of Parkinson's disease.
AB  - Many studies have shown that deficits in olfactory and cognitive functions
      precede the classical motor symptoms seen in Parkinson's disease (PD) and that
      olfactory testing may contribute to the early diagnosis of this disorder.
      Although the primary cause of PD is still unknown, epidemiological studies have
      revealed that its incidence is increased in consequence of exposure to certain
      environmental toxins. In the present study, we demonstrated that rats treated
      with intranasal infusion of the neurotoxin 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP) at low concentrations (0.1 mg/nostril) suffered
      progressive impairments in olfactory, cognitive and motor functions that were
      assessed with the olfactory discrimination, Morris water maze and open field
      tests, respectively. Moreover, intranasal administration of MPTP reduced the
      expression of the enzyme tyrosine hydroxylase in the olfactory bulb and
      substantia nigra of rats, resulting in a significant reduction of dopamine
      concentration in the olfactory bulb, prefrontal cortex and striatum, but not in
      the hippocampus. These results reinforce the notion that the olfactory system
      represents a particularly sensitive route for the transport of neurotoxins into
      the central nervous system that may be related to the etiology of PD. In
      addition, the time course of the olfactory, cognitive and motor impairments
      verified in rats treated intranasally with MPTP, which appears to be correlated
      with different stages of the human PD, suggest that the MPTP intranasal model in
      rats may provide new insights into the underlying mechanisms of PD pathogenesis.

PMID- 16908023
TI  - Effect of hypernatraemia and the neurohypophysial peptide, arginine vasotocin
      (AVT) on behavioural thermoregulation in the agamid lizard, Ctenophorus ornatus.
AB  - Hypernatraemia induced by chronic injections of sodium chloride provokes thermal
      depression in the agamid lizard, Ctenophorus (formerly Amphibolurus) ornatus,
      with a fall of two degrees Celsius in the mean body temperature selected
      behaviourally in a photo-thermal gradient. The placement of an electrolytic
      lesion in the base of the hypothalamus, designed to eliminate secretion of the
      neuropeptide arginine vasotocin (AVT), did not affect the lizards'
      thermoregulatory behaviour and their Preferred Body Temperature (PBT) was not
      significantly different from that of unoperated controls. Saline loading,
      however, did not induce thermal depression in these tract-operated individuals
      and their PBT was significantly higher than that of salt-loaded intact
      individuals. When AVT was injected into operated, salt-loaded, animals, however,
      thermal depression was observed, supporting the hypothesis that thermal
      depression brought about by hypernatraemia is mediated through the action of AVT.
      AVT similarly significantly depressed the PBT of injected intact individuals by
      3.2 degrees C when compared with hydrated controls. Immunostaining for AVT
      confirmed that the lesions placed in the region of the median eminence virtually
      eliminated AVT located in the neurohypophysial tract, and the pars nervosa. This
      is the first report of an effect of this peptide on behavioural thermoregulation
      in a lizard.

PMID- 16908022
TI  - Toxocara canis: effect of inoculum size on pulmonary pathology and cytokine
      expression in BALB/c mice.
AB  - Infection of mice with Toxocara canis results in pulmonary inflammation and the
      induction of a Th2 type of immune response. The aim of this study was to
      determine whether the effect of infection with this nematode depends on the
      inoculum size. Results indicate that mice infected with either a high or a low
      inoculum size showed, in a dose-dependent manner, pulmonary inflammation with
      eosinophil infiltration, increased levels of total IgE, and Toxocara-specific
      IgG1 that persisted up to 60 days p.i. Relative quantification of cytokine
      expression in lungs of mice infected with different doses showed proportional
      increased expression of the IL-4, IL-5, and IL-10 transcripts, whereas the
      expression of the IFN-gamma transcript was not different from that of uninfected
      controls. These results indicate that infection of BALB/c mice with T. canis
      results in chronic pulmonary inflammation and a dominant Th2 type of immune
      response, independent of the inoculum size.

PMID- 16908024
TI  - Diagnostic value of carotid intima-media thickness in indicating multi-level
      atherosclerosis.
AB  - Carotid intima-media thickness (CIMT) is an indicator of atherosclerosis, but its
      association with multi-level involvement is sparsely investigated. Study aimed to
      examine interrelation between CIMT and number of arterial territories with
      significant (>50%) stenoses, including coronary, supraaortic, renal and
      iliac/femoral arteries. METHODS AND RESULTS: Study formed 415 patients (294 men),
      aged 62.9+/-9.3 years referred to coronary angiography. CIMT assessment was
      performed in common, bulb and internal carotid segments, and expressed as the
      mean aggregate value. In all patients, both coronary, renal angiography and
      supraaortic, iliac/femoral arteries ultrasound was performed. Group I formed 102
      patients without significant lesions in any of investigated territories; group II
      formed 131 patients with single territory; group III formed 102 patients with two
      territory and group IV formed 80 patients with three to four territory
      involvements. CIMT correlated with increasing number of involved territories
      (r=0.751, p<0.001). Aggregate CIMT, previous myocardial infarction, creatinine
      level, hypertension, hs-CRP, smoking were independent predictors of multi-level
      involvement (p<0.001, R=0.768). ROC curves showed that CIMT cut-off value of
      1.308 mm could distinguish 0-1 from two to three level involvement with
      sensitivity of 81.6%, specificity 88.8%, PPV 85.1%, NPV 86.3% (odds ratio 35.9,
      range 20-65). CONCLUSIONS: CIMT increases with number of involved territories.
      CIMT is an independent predictor of significant multi-level atherosclerosis,
      showing high sensitivity and specificity for indicating more advanced territorial
      atherosclerotic involvement.

PMID- 16908025
TI  - G-protein beta3 subunit (GNB3) gene polymorphisms and cardiovascular disease: the
      Ludwigshafen Risk and Cardiovascular Health (LURIC) study.
AB  - A common 825C>T polymorphism in exon 10 of the gene for the beta-3 subunit of
      heterotrimeric G-proteins, GNB3, has been associated in some studies with traits
      of the metabolic syndrome as well as coronary artery disease (CAD), but these
      associations were refuted by other studies. To investigate the role of GNB3 gene
      variations in CAD and myocardial infarction (MI), we determined five GNB3
      polymorphisms (-1429G>A, IVS5 +41G>A, 657T>A, 814G>A and 825C>T) in the
      Ludwigshafen Risk and Cardiovascular Health (LURIC) cohort, including 2575
      patients with angiographically documented CAD and 731 individuals in whom CAD had
      been ruled out by angiography. None of the GNB3 polymorphisms was associated with
      CAD, MI, diabetes, hypertension, blood pressure, body weight or body mass index.
      We conclude that a major contribution of GNB3 gene variants to CAD or MI risk is
      unlikely.

PMID- 16908026
TI  - The limits of the separation power of unidimensional column liquid
      chromatography.
AB  - The practical limit of the separation power of HPLC depends on time, money, and
      skill. That is it depends on the time available for the analysis, on the quality
      and performance of the pump and hardware and particularly on the maximum pressure
      at which the pump can deliver the mobile phase to the column, and on the
      temperature at which the column can be operated. It also depends on the
      properties of the packing material selected (e.g., its particle size, its pore
      geometry, and its connectivity) and on the packing method used since it affects
      the coefficients of the HETP equation. Finally, it depends on the thermal
      stability of the sample and the packing material. The complexity of the sample
      also plays an important role in that it determines whether the analysis should be
      made under isocratic, isothermal conditions, in gradient elution, in temperature
      programming, or with a combination of both types of programming. The various
      phenomena that affect column properties and separation performance are discussed.
      Past achievements suggest that columns providing efficiencies in excess of a
      million plates in less than 1 day are within the grasp of current technology. The
      possibility of further advances are considered.

PMID- 16908027
TI  - Field resistance of codling moth against Cydia pomonella granulovirus (CpGV) is
      autosomal and incompletely dominant inherited.
AB  - The current appearance of local codling moth populations with resistance to Cydia
      pomonella granulovirus (CpGV) is an impediment to continuous CpGV application.
      Therefore, crossing experiments have been performed in order to gain information
      about the inheritance of resistance. Evidence is presented that the observed
      field resistance is stably inherited even under non-selective conditions in the
      laboratory. Offspring of reciprocal F(1) crosses between a susceptible ('S') and
      a resistant ('R') strain and backcrosses between F(1) and S were bioassayed at
      different CpGV concentrations. The resistant strain showed 100 times lower
      susceptibility in 7-day bioassays. The responses of the reciprocal crosses (male
      S x female R and female S x male R) did not differ significantly, indicating that
      resistance is autosomally inherited. The median lethal concentration for the F(1)
      progeny was intermediate between those of its parental strains. Mortality data
      obtained from the backcrosses suggested that inheritance of resistance is due to
      a non-additive, polygenic trait.

PMID- 16908028
TI  - Ras: the stress and the strain.

PMID- 16908029
TI  - Folding of the repeat domain of tau upon binding to lipid surfaces.
AB  - The microtubule-associated protein tau is impacted in neurodegeneration and
      dementia through its deposition in the form of paired helical filaments in
      Alzheimer's disease neurofibrillary tangles and through mutations linking it to
      the autosomal dominant disorder frontotemporal dementia with Parkinsonism. When
      isolated in solution tau is intrinsically unstructured and does not fold, while
      the conformation of the protein in the microtubule-bound state remains
      uncharacterized. Here we show that the repeat region of tau, which has been
      reported both to mediate tau microtubule interactions and to constitute the
      proteolysis-resistant core of disease-associated tau aggregates, associates with
      lipid micelles and vesicles and folds into an ordered structure upon doing so. In
      addition to providing the first structural insights into a folded state of tau,
      our results support a role for lipid membranes in mediating tau function and tau
      pathology.

PMID- 16908030
TI  - Selective anterior cingulate cortex deficit during conflict solution in
      schizophrenia: an event-related potential study.
AB  - BACKGROUND: Schizophrenia research has gained a new focus on identification and
      further characterization of neurocognitive deficits in the search for behavioural
      endophenotypes of this disorder. The objective of this study was to explore
      differential cortical processing during executive control in schizophrenia as
      assessed with the attention network test (ANT). METHODS: Sixteen schizophrenic
      patients and sixteen healthy controls matched for gender, age, education, and
      nicotine consumption were tested with the ANT while recording 29-channel
      electroencephalogram (EEG). Visual event-related potentials (ERP) N200 and P300
      were topographically analyzed and cortical mapping using low resolution brain
      electromagnetic tomography (LORETA) was applied to localize neuroelectric
      generators of ERP. RESULTS: Behaviourally, significant differences between
      schizophrenic patients and controls were found only for the conflict condition
      (p<0.05) and for conflict adjusted by mean reaction time (p<0.01). Examining ERP
      of control subjects, N200 failed to show robust flanker congruency effects. P300
      amplitude was reduced at Pz (p<0.05) and P300 latency was increased at Cz
      (p<0.005) for the conflict condition. Schizophrenic patients differed
      significantly in P300 latency at Cz during late conflict processing (p<0.005).
      Source analysis revealed a deficit in anterior cingulate cortex (p<0.05).
      CONCLUSION: Our results are in line with previous reports about dysfunctional ACC
      activation in schizophrenia and argue in favour of a selective deficit of
      cortical conflict resolution. It is further proposed that dysfunctional ACC
      activation during executive processing may be a neurophysiologic endophenotype
      candidate of schizophrenia.

PMID- 16908031
TI  - Evolution of talking plants in a tritrophic context: conditions for uninfested
      plants to attract predators prior to herbivore attack.
AB  - Herbivory induces plants to emit volatile chemicals that attract enemies of the
      herbivores (bodyguards of plants). In this way, the plant acquires protection and
      the bodyguards gain food. These plant signals cause neighboring plants, not under
      attack, to release signals as well. We hypothesize that such "secondary" signals
      help to reduce damage from future herbivore attacks by the protection received
      from the bodyguards. By modeling we explore the conditions for such secondary
      signals to evolve. Three kinds of strategies are considered: plants of the first
      strategy always emit a signal, those of the second strategy emit a signal only
      when infested, and those of the third strategy emit a signal not only when
      infested, but also when a certain number of neighbors are infested (i.e.
      secondary signaling). When signaling is much less (much more) costly than damage
      from herbivory, the first (second) strategy will be favored by selection, whereas
      for intermediate costs the third strategy, i.e. secondary signaling, will evolve.
      However, secondary signaling will not evolve when the primary signals lure the
      bodyguards too effectively. This is because the undamaged plant gains
      associational defense when the infested individual is defending very well;
      therefore, the need for secondary signaling decreases.

PMID- 16908032
TI  - Using pseudo-amino acid composition and support vector machine to predict protein
      structural class.
AB  - As a result of genome and other sequencing projects, the gap between the number
      of known protein sequences and the number of known protein structural classes is
      widening rapidly. In order to narrow this gap, it is vitally important to develop
      a computational prediction method for fast and accurately determining the protein
      structural class. In this paper, a novel predictor is developed for predicting
      protein structural class. It is featured by employing a support vector machine
      learning system and using a different pseudo-amino acid composition (PseAA),
      which was introduced to, to some extent, take into account the sequence-order
      effects to represent protein samples. As a demonstration, the jackknife cross
      validation test was performed on a working dataset that contains 204 non
      homologous proteins. The predicted results are very encouraging, indicating that
      the current predictor featured with the PseAA may play an important complementary
      role to the elegant covariant discriminant predictor and other existing
      algorithms.

PMID- 16908033
TI  - Inactivation of H+-vacuolar ATPase by the energy blocker 3-bromopyruvate, a new
      antitumour agent.
AB  - 3-bromopyruvate (3-Br PA), a strong alkylating agent, was found to cause a
      dramatic disruption of pH gradients in acidic compartments of Ehrlich ascites
      tumour cells (EATCs), as well as of rat thymocytes, at concentrations similar to
      those reported to cause ATP depletion in hepatocellular carcinoma cells. However,
      in the condition of complete disruption of pH gradients, ATP depletion was not,
      in either cell type, as serious as pH gradient dissipation. Moreover, the 3-Br PA
      effect on acidic compartments preceded severe cell ATP depletion, indicating that
      the former was not merely linked to energy deprivation elicited by 3-Br PA.
      Experiments conducted on isolated lysosomes supported this view in that the drug
      inactivated H(+)-vacuolar ATPase, the enzyme that makes certain compartments in
      the cell acidic. Inactivation probably involved alkylation of the enzyme on a
      thiol group, essential for H(+)-ATPase activity for dithiothreitol secured
      complete protection from 3-Br PA inactivation. The findings are discussed with
      regards to a possible involvement of lysosome destabilization in 3-Br PA induced
      cell death.

PMID- 16908034
TI  - Trace organic contamination in biota collected from the Pearl River Estuary,
      China: a preliminary risk assessment.
AB  - The marine ecosystem of the Pearl River Delta, located on the southern coast of
      China, has been heavily exploited following the rapid economic growth that has
      occurred since the 1980s. This investigation aimed to elucidate trace organic
      contamination in marine biota inhabiting the Pearl River Delta area. Biota
      samples, including green-lipped mussels (Perna viridis), oysters (Crassostrea
      rivularis) and shrimp (Penaeus orientalis) were sampled from 16 stations fringing
      the Estuary. Elevated concentrations (on a dry weight basis) of polycyclic
      aromatic hydrocarbons (27.8-1041.0 ng/g), petroleum hydrocarbons (1.7-2345.4
      microg/g), polychlorinated biphenyls (2.1-108.8 ng/g), DDTs (1.9-79.0 ng/g), and
      hexachlorocyclohexanes (n.d.-38.4 ng/g) were recorded. A human health risk
      assessment was conducted to estimate the risk to local residents associated with
      the consumption of biota collected from the Pearl River Estuary. The results
      indicated that PCBs were at levels that may cause deleterious health effects in
      populations that consume large amounts of seafood. However, it would be
      instructive to establish health criteria for trace organic contaminants that are
      specific to the local populations, in order to derive a more accurate and
      relevant health risk assessment.

PMID- 16908035
TI  - Trawling the sea bed.

PMID- 16908036
TI  - Evolution of linkage disequilibrium of the founders in exponentially growing
      populations.
AB  - Evolution of linkage disequilibrium of the founders in exponentially growing
      populations was studied using a time-inhomogeneous Ito process model. The model
      is an extension of the diffusion approximation of the Wright-Fisher model. As a
      measure of linkage disequilibrium, the squared standard linkage deviation, which
      is defined by a ratio of the moments, was considered. A system of ordinary
      differential equations that these moments obey was obtained. This system can be
      solved numerically. By simulations, it was shown that the squared standard
      linkage deviation gives a good approximation of the expectation of the squared
      correlation coefficient of gamete frequencies. In addition, a perturbative
      solution was obtained when the growth rate is not large. By using the
      perturbation, an asymptotic formula for the squared standard linkage deviation
      after a large number of generations was obtained. According to the formula, the
      squared standard linkage deviation tends to be 1/(4Nc), where N is the current
      size of the population and c is the recombination fraction between two loci. It
      is dependent on neither the initial effective size, the growth rate, nor the
      mutation rate. In exponentially growing populations, linkage disequilibrium will
      be asymptotically the same as that in a constant size population, the effective
      size of which is the current effective size.

PMID- 16908037
TI  - Multiple regression analysis as a tool for the identification of relations
      between semi-quantitative LC-MS data and cytotoxicity of extracts of the fungus
      Fusarium avenaceum (syn. F. arthrosporioides).
AB  - The cytotoxicity of methanolic extracts from rice cultures of 53 Fusarium
      avenaceum strains, which had been isolated from different host organisms in
      Northern Europe, Canada and Australia/New Zealand, was investigated in a rat
      hepatoma (H4IIE-W), porcine epithelial kidney (PK-15), foetal feline lung
      fibroblast, dog lymphoblast (D3447), and a human hepatocarcinoma (Hep G2) cell
      line using the Alamar Bluetrade mark assay. All extracts were screened for known
      fungal metabolites using high-performance liquid chromatography with photodiode
      array and mass spectrometric detection, and both known and unknown metabolites
      were semi-quantified. Known metabolites that were determined in the cultures
      include acuminatopyrone, 2-amino-14,16-dimethyloctadecan-3-ol (2-AOD-3-ol),
      antibiotic Y, aurofusarin, chlamydosporol, chlamydospordiol, enniatins, fusarin A
      and C, and moniliformin. Multiple regression analysis was used in order to relate
      fungal metabolites to the cytotoxicity of the extracts. Separate linear
      regression models were constructed for each cell line. Eleven different fungal
      metabolites were related to the cytotoxicity (P<0.05). Out of these, nine
      metabolites were siginificantly related to the cytotoxicity in only one of the
      five models, while two, namely enniatins and 2-AOD-3-ol, were significant
      contributors in three or four regression models, respectively. This paper
      describes how multiple regression analysis may be applied for the assignment of
      bioactivity/toxicity to the constituents of a multi-component mixture.

PMID- 16908038
TI  - Primary structure of a thrombin-like serine protease, kangshuanmei, from the
      venom of Agkistrodon halys brevicaudus stejneger.
AB  - The complete amino acid sequence of the thrombin-like serine protease, named
      kangshuanmei, isolated from the venom of a Chinese snake Agkistrodon halys
      brevicaudus stejneger, was determined by Edman degradation. The serine protease
      was composed of 236 amino acid residues and conserved the catalytic triad as
      His43, Asp88 and Ser182. The protease had four sites of asparagine-linked
      glycosylation at 81, 99, 148 and 229, and contained fucose, N-acetylglucosamin,
      galactose, mannose and N-acetylneuraminic acid. The amino acid sequence exhibited
      considerable similarities with other thrombin-like proteases isolated from the
      snake venoms of the Viperidae family. However, the enzymatic characteristics of
      kangshuanmei distinct from that of thrombin and the other protease from the venom
      of Viperidae family may be derived from the structural difference of the sequence
      in the functional regions, especially corresponding to thrombin exosite 1, 2 and
      hydrophobic pocket.

PMID- 16908039
TI  - Estimation of HIFU induced lesions in vitro: numerical simulation and experiment.
AB  - The heated necrotic element created by a single high intensity focused ultrasound
      exposure can be considered as the foundation of high intensity focused ultrasound
      ablation of tumour lesions. In this paper, we studied the effects of exposure
      dose and focal depth in tissue on heated necrotic elements, using numerical
      simulation and experiment. The acoustic field of one of the transducers for the
      Model-JC HAIFU focused ultrasound tumour therapeutic system was modeled using O
      Neill's equation, and then using this information together with Pennes' bio-heat
      transfer-equation and finite difference techniques, the heated necrotic element
      was simulated numerically. The results showed that the theoretical predictions
      were basically in agreement with the experimental data for low exposures, but
      that the experimental values suddenly increased with the increasing exposure and
      exceeded the theoretical predictions. The element volume from the theoretical
      prediction and experiment for the heated necrotic element decreased with
      increasing focal depth in tissue for a given exposure, and the theoretical
      predictions were a little lower than the experimental ones. Therefore, heated
      necrotic elements created by high intensity focused ultrasound can be well
      predicted from a knowledge of ultrasonic biophysics theories.

PMID- 16908040
TI  - Needle and seed segmentation in intra-operative 3D ultrasound-guided prostate
      brachytherapy.
AB  - In order to guide the needle to the correct location in 3D US-guided
      brachytherapy, the needle is continuously tracked as it is being inserted. A pre
      scan before the needle insertion and a post-scan after the needle insertion are
      subtracted to obtain a difference image containing the needle. The image is
      projected along two orthogonal directions approximately perpendicular to the
      needle, and the 3D needle is reconstructed from the segmented needles in the two
      projected images. The seeds implanted with the needle are located in the cropped
      volume along the needle. Thus, the seeds are segmented using a tri-bar model and
      3D line segment patterns. Finally, the positions of the seeds are determined
      using a peak detection technique. Experiments with agar and turkey/chicken
      phantoms as well as patient data demonstrated that our needle segmentation
      technique could segment the needle in near real-time with an accuracy of 0.6 mm
      in position and 1.0 degrees in orientation. The true-positive rate for seed
      segmentation is 100% for the agar phantom and 93% for the chicken phantom. The
      average distance to manual seed segmentation was 1.0mm for the agar phantom and
      1.7 mm for the chicken phantom.

PMID- 16908041
TI  - Modeling of interaction between therapeutic ultrasound propagation and cavitation
      bubbles.
AB  - In medical applications of high intense focused ultrasound the mechanism of
      interaction between ultrasound waves and cavitation bubbles is responsible for
      several therapeutic effects as well as for undesired side effects. Based on a two
      phase continuum approach for bubbly liquids, in this paper a numerical model is
      presented to simulate these interactions. The numerical results demonstrate the
      influence of the cavitation bubble cloud on ultrasound propagation. In the case
      of a lithotripter pulse an increased bubble density leads to significant changes
      in the tensile part of the pressure waveform. The calculations are verified by
      measurements with a fiber optical hydrophone and by experimental results of the
      bubble cloud dynamics.

PMID- 16908042
TI  - Identification of a novel virulence determinant within the E2 structural
      glycoprotein of classical swine fever virus.
AB  - Classical swine fever virus (CSFV) E2 glycoprotein contains a discrete epitope
      (TAVSPTTLR, residues 829-837 of CSFV polyprotein) recognized by monoclonal
      antibody (mAb) WH303, used to differentiate CSFV from related ruminant
      pestiviruses, Bovine Viral Diarrhea Virus (BVDV) and Border Disease Virus (BDV),
      that infect swine without causing disease. Progressive mutations were introduced
      into mAb WH303 epitope in CSFV virulent strain Brescia (BICv) to obtain the
      homologous amino acid sequence of BVDV strain NADL E2 (TSFNMDTLA). In vitro
      growth of mutants T1v (TSFSPTTLR), T2v (TSFNPTTLR), T3v (TSFNMTTLR) was similar
      to parental BICv, while mutants T4v (TSFNMDTLR) and T5v (TSFNMDTLA) exhibited a
      10-fold decrease in virus yield and reduced plaque size. In vivo, T1v, T2v or T3v
      induced lethal disease, T4v induced mild and transient disease and T5v induced
      mild clinical signs. Protection against BICv challenge was observed at 3 and 21
      days post-T5v infection. These results indicate that E2 residues TAVSPTTLR play a
      significant role in CSFV virulence.

PMID- 16908044
TI  - Multiple determinants in the coding region of Pea seed-borne mosaic virus P3 are
      involved in virulence against sbm-2 resistance.
AB  - Viral determinants for overcoming Pisum sativum recessive resistance, sbm-2,
      against the potyvirus Pea seed-borne mosaic virus (PSbMV) were identified in the
      region encoding the N-terminal part of the P3 protein. Codons conserved between
      sbm-2 virulent isolates in this region: Q21, K30 and H122 were found to
      specifically impair sbm-2 virulence when mutated in selected genetic backgrounds.
      The corresponding amino acids, Gln21 and Lys30, are neighbored by P3 residues
      strongly conserved among potyviruses and His122 is conserved particularly in
      potyviral species infecting legumes. The strongest selective inhibition of sbm-2
      virulence, however, was observed by elimination of isolate specific length
      polymorphisms also located in the N-terminal part of the P3 protein. Length
      variation in N-terminal P3 is common between potyviral species. However, intra
      species length polymorphism in this region was found only among PSbMV isolates.
      Our findings comply with a model for PSbMV pathotypes having evolved by a
      diversification of the P3 protein likely to extend to the level of function.

PMID- 16908045
TI  - The effect of groundwater composition on uranium(VI) sorption onto bacteriogenic
      iron oxides.
AB  - In this study, we investigated the effect of groundwater composition on the
      sorption of U(VI) onto bacteriogenic iron oxides (BIOS) and synthetic
      ferrihydrite (HFO). The concentration of carbonate was found to be the key factor
      controlling U(VI) sorption onto both BIOS and HFO. However, the efficiency of HFO
      to adsorb uranium(VI) was higher than that of BIOS at pH 7.0. The pH value also
      played an important role on the U(VI) sorption onto iron oxides. U(VI) sorption
      onto BIOS was optimum in the pH range 3-4.5, whereas in the same pH range, the
      ability of HFO to adsorb U(VI) was very low. HFO was very efficient in adsorbing
      U(VI) in the pH range 4.5-6.5. Zeta potential measurements have been employed to
      understand the different removal trends between BIOS and HFO. BIOS had a negative
      surface charge across the whole pH range examined, in contrast to HFO, which had
      point of zero charge 7.6. The sorption results have been incorporated in a
      surface complexation model, which predicted adequately the pH-dependent sorption
      of U(VI) onto both types of iron oxides.

PMID- 16908043
TI  - Induction of transcription factor Egr-1 gene expression in astrocytoma cells by
      Murine coronavirus infection.
AB  - Mouse hepatitis virus (MHV) causes encephalitis and demyelination in the central
      nervous system (CNS) of susceptible rodents. Astrocytes are one of the major
      targets for MHV infection in the CNS, and respond to MHV infection by expressing
      diverse molecules that may contribute to CNS pathogenesis. Here we characterized
      the activation of an immediate-early transcription factor Egr-1 by MHV infection
      in an astrocytoma cell line. We found that the expression of Egr-1 was
      dramatically increased following virus infection. Using various inhibitors of
      mitogen-activated protein kinases, we identified that the extracellular signal
      regulated kinases 1/2 were involved in the activation of Egr-1 transcription by
      MHV infection. Experiments with ultraviolet light-inactivated virus revealed that
      the induction of Egr-1 did not require virus replication and was likely mediated
      during cell entry. We further found that over-expression of Egr-1 suppressed the
      expression of BNip3, a pro-apoptotic member of the Bcl-2 family. This finding may
      provide an explanation for our previously observed down-regulation of BNip3 by
      MHV infection in astrocytoma cells (Cai, Liu, Yu, and Zhang, Virology 316:104
      115, 2003). Furthermore, knockdown of Egr-1 by an siRNA inhibited MHV
      propagation, suggesting the biological relevance of Egr-1 induction to virus
      replication. In addition, the persistence/demylinating-positive strains (JHM and
      A59) induced Egr-1 expression, whereas the persistence/demylinating-negative
      strain (MHV-2) did not. These results indicate a correlation between the ability
      of MHVs to induce Egr-1 expression and their ability to cause demyelination in
      the CNS, which may suggest a potential role for the induction of Egr-1 in viral
      pathogenesis.

PMID- 16908046
TI  - DNA extraction and Escherichia coli quantification of anaerobically digested
      biosolids using the competitive touchdown PCR method.
AB  - Accurate enumeration of indicator organisms such as Escherichia coli is important
      for assessing the safety of water and wastewater samples. Recent research has
      shown that E. coli can enter a viable but non-culturable state; therefore,
      traditional cultivation methods could potentially underestimate the quantities of
      the organisms. The goals of the research were to develop and verify a DNA
      extraction protocol and a quantitative polymerase chained reaction (PCR) method
      for E. coli enumeration in digested biosolids. A solvent-based DNA extraction
      protocol with extensive cell lysis recovered approximately 78-84% of spiked DNA.
      In comparison, a commercial kit only recovered 28-42% of DNA, likely from
      inefficient cell lysis. The developed competitive touchdown PCR (cPCR) method for
      E. coli enumeration was comparable to both real-time PCR (rt-PCR) and cultivation
      methods with sensitivity of approximately 50,000-500,000 E. coli per gram dry
      solids (DS), which is suitable for Class B biosolids monitoring in the US and
      "conventional" biosolids in the European Union. The cPCR protocol provides a less
      expensive alternative than the rt-PCR as a culturing independent method for
      enumerating E. coli.

PMID- 16908047
TI  - Remediation of heavy metal polluted sediment by suspension and solid-bed
      leaching: estimate of metal removal efficiency.
AB  - Remediation of heavy metal polluted sediment by extracting the metals with
      sulfuric acid can be performed as follows: abiotic suspension leaching, microbial
      suspension leaching, abiotic solid-bed leaching, and microbial solid-bed
      leaching. Abiotic leaching means that the acid is directly added, while microbial
      leaching means that the acid is generated from sulfur by microbes (bioleaching).
      These four principles were compared to each other with special emphasis on the
      effectiveness of metal solubilization and metal removal by subsequent washing.
      Abiotic suspension leaching was fastest, but suspending the solids exhibits some
      disadvantages (low solid content, costly reactors, permanent input of energy,
      high water consumption, special equipment required for solid separation, large
      amounts of waste water, sediment properties hinder reuse), which prevent
      suspension leaching in practice. Abiotic solid-bed leaching implies the supply of
      acid by percolating water which proceeds slowly due to a limited bed
      permeability. Microbial solid-bed leaching means the generation of acid within
      the bed and has been proven to be the only principle applicable to practice.
      Metal removal from leached sediment requires washing with water. Washing of solid
      beds was much more effective than washing of suspended sediment. The kinetics of
      metal removal from solid beds 0.3, 0.6 or 1.2m in height were similar; when using
      a percolation flow of 20lm(-2)h(-1), the removal of 98% of the mobile metals
      lasted 57-61h and required 8.5, 4.2 or 2.3lkg(-1) water. This means, the higher
      the solid bed, the lower the sediment-mass-specific demand for time and water.

PMID- 16908048
TI  - Predicting diffuse-source transfers of surfactants to surface waters using SWAT.
AB  - Chemicals present in domestic wastewater can adsorb to solid phase materials
      during sewage treatment. If biosolids (or sewage sludge) are applied to land,
      these chemicals can be transferred to soil. Under some circumstances they can
      also be transferred to surface waters during storm events either in solution or
      attached to sediment. In this paper we describe the utility of the SWAT 2000
      model to estimate diffuse-source surface water exposure to "down-the-drain"
      chemicals. The model was applied hypothetically to predict the behaviour of
      linear alkylbenzene sulphonate (LAS), an anionic surfactant commonly used in
      household detergents, in a small catchment in Bedfordshire, UK, where it has
      previously been successfully validated for stream flow, sediments and pesticides.
      LAS transfers were estimated for two scenarios: (1) realistic and (2) reasonable
      worst case, based on assumptions on sludge application rates and the
      concentration of LAS in sludge. In addition, the sensitivity of the model output
      to the proportion of the catchment to which sludge is applied was established.
      Soil wetness and the total quantity of biosolids applied were the biggest
      determinants of chemical transport from the catchment. The potential of SWAT as a
      higher-tier tool in environmental risk assessments is discussed.

PMID- 16908049
TI  - Simultaneous determination of gaseous and particulate chlorinated polycyclic
      aromatic hydrocarbons in emissions from the scorching of polyvinylidene chloride
      film.
AB  - An analytical method for the determination of gaseous and particulate chlorinated
      polycyclic aromatic hydrocarbons (ClPAHs) was investigated. By means of this
      method, concentrations and isomer profiles of the 27 target ClPAHs could be
      analyzed. To evaluate the usefulness of the method for analyzing ClPAH emissions,
      laboratory-scale scorching tests were performed on polyvinylidene chloride (PVDC)
      plastic wrap over a flame of the gas burner. Only seven of the target ClPAHs were
      detected, and all compounds detected had 2, 3, or 4 rings. The detected ClPAHs
      were present in both the particulate phase and the gaseous phase, but they were
      present at higher concentrations in the gaseous phase than in the particulate
      phase. Relationships between the number of chlorine substituents on the
      naphthalene/phenanthrene rings and the overall concentration and the percentage
      in the particulate phase were also investigated.

PMID- 16908050
TI  - Development of a biotic ligand model (BLM) predicting nickel toxicity to barley
      (Hordeum vulgare).
AB  - A biotic ligand model (BLM) was developed to predict nickel toxicity, affecting
      root growth of barley (Hordeum vulgare), in nutrient solutions. The extent to
      which Ca(2+), Mg(2+), Na(+), K(+) ions and pH each influenced nickel toxicity was
      determined. Higher activities of Mg(2+) linearly increased the 4d EC50 Ni (2+) ,
      while Ca(2+), Na(+), K(+) and H(+) activities did not significantly influence
      Ni(2+) toxicity. Stability constants for the binding of Ni(2+) and Mg(2+) to the
      biotic ligand were obtained: logK(NiBL)=5.27 and logK(MgBL)=3.47. Further, it was
      calculated that on average 57% of the biotic ligand sites needed to be occupied
      by nickel to induce 50% root growth inhibition. Auto-validation of the BLM
      indicated that predicted EC50s differed from the observed EC50s by a factor of
      less than 2, indicating that the BLM concept may also be used to predict metal
      toxicity to terrestrial plants.

PMID- 16908051
TI  - Diet and behavior of the Saint-Cesaire Neanderthal inferred from biogeochemical
      data inversion.
AB  - Biogeochemistry is a powerful tool for dietary reconstruction, and mixing
      equations can be used to quantify the contribution of multiple sources to an
      individual's diet. The goals of this paper are: 1) to generalize the inverse
      method to dietary mixtures; and 2) to reconstruct the diet of the Saint-Cesaire
      Neanderthal using Sr/Ca and Ba/Ca data of the mineral fraction of bone
      (hydroxylapatite), and with published delta13C and delta15N data of the
      associated organic fraction of bone (collagen). A new method is proposed to
      calculate the maximum diagenetic contribution of the Sr/Ba ratio, assuming that
      the soil soluble fraction is the diagenetic end-member and, for a given fraction
      of diagenesis, allows the restoration of the original Sr/Ba ratio. Considering
      the Saint-Cesaire Chatelperronian mammalian assemblage as the meat source, and on
      the basis of available Sr, Ba, and Ca contents of plants, the results indicate
      that the percentage of plants in the Neanderthal's diet must have been close to
      zero for realistic Sr and Ba impoverishment between diet and hydroxylapatite.
      Contrary to previous studies, it is shown that fish could constitute a
      significant proportion (30%) of the diet of the Saint-Cesaire Neanderthal.
      However, this mass balance solution is not supported by the zooarchaeological
      data. When the entire faunal assemblage is considered as the dietary source, the
      calculation shows that bovids (except reindeer) represent the greatest percentage
      of consumed meat (58%), followed by horses/rhinoceros (22%), reindeer (13%), and
      mammoths (7%). These respective percentages are in close accordance with
      zooarchaeological records, suggesting that the faunal assemblage associated with
      the Neanderthal of Saint-Cesaire reliably reflects what he ate during the last
      few years of his life. In behavioral terms, this result supports the hypothesis
      that this Neanderthal carried the foodstuffs back to the Saint-Cesaire shelter
      before their consumption.

PMID- 16908052
TI  - Dental microwear texture analysis: technical considerations.
AB  - Dental microwear analysis is commonly used to infer aspects of diet in extinct
      primates. Conventional methods of microwear analysis have usually been limited to
      two-dimensional imaging studies using a scanning electron microscope and the
      identification of apparent individual features. These methods have proved time
      consuming and prone to subjectivity and observer error. Here we describe a new
      methodological approach to microwear: dental microwear texture analysis, based on
      three-dimensional surface measurements taken using white-light confocal
      microscopy and scale-sensitive fractal analysis. Surface parameters for
      complexity, scale of maximum complexity, anisotropy, heterogeneity, and textural
      fill volume offer repeatable, quantitative characterizations of three-dimensional
      surfaces, free of observer measurement error. Some results are presented to
      illustrate how these parameters distinguish extant primates with different diets.
      In this case, microwear surfaces of Cebus apella and Lophocebus albigena, which
      consume some harder food items, have higher average values for complexity than do
      folivores or soft fruit eaters.

PMID- 16908053
TI  - Direct, reverse or reciprocal causation in the relation between homocysteine and
      ischemic heart disease.
AB  - BACKGROUND: Whether mild hyperhomocysteinemia is a risk factor for ischemic heart
      disease (IHD) or it is a secondary epiphenomenon remains unknown. We tested the
      alternative hypotheses that the Hcy-IHD relation is due to direct, reversal or
      reciprocal causality. METHODS: Ninety-four families from 32 pedigrees (296
      members) including subjects who died for a premature (<50 years) IHD and with at
      least one family member with also a premature IHD were selected. Three Structural
      Equation Models were created, in which causal (Model 1), reversal (Model 2), and
      reciprocal (Model 3) tHcy-IHD relation were tested. Results were confirmed by
      testing "Pearl's instrumental inequalities". RESULTS: A significant tHcy-IHD
      association was found in Model 1 (OR=1.38, 95% CI: 1.01 to 1.88, for any increase
      of +10 micromol/l in tHcy), as opposed to a non-significant association in the
      other models (Model 2: MD=+1.63 micromol/l, 95% CI: -1.72 to +4.99 micromol/l;
      Model 3: OR=0.69, 95% CI: 0.17 to 2.78 for tHcy predictor of IHD; MD=-0.46
      micromol/l, 95% CI: -2.41 to 1.48 micromol/l, for IHD predictor of tHcy).
      "Pearl's instrumental inequalities" qualify MTHFR as an instrument relative to
      the tHcy-IHD relation. A suppression effect may explain the non-significant total
      MTHFR-IHD relation (OR=1.275, 95% CI: 1.02 to 1.71 for the indirect MTHFR-tHcy
      IHD path; OR=0.52, 95% CI: 0.17 to 1.64 for the direct MTHFR-IHD path).
      CONCLUSION: Our findings support the assumption of a triangular genotype
      phenotype-disease mediation process in the Hcy-IHD relation, and indirectly, of a
      causal relationship between moderately elevated plasma tHcy levels and IHD.

PMID- 16908054
TI  - Adenovirus-mediated transfer of human papillomavirus 16 E6/E7 antisense RNA and
      induction of apoptosis in cervical cancer.
AB  - OBJECTIVE: In most cervical cancers, human papillomaviruses (HPVs) are
      identified. The E6 and E7 genes of HPVs encode proteins, that interfere with the
      function of the tumor suppressor proteins p53 and Rb. We are exploring the
      potential use of antisense HPV RNA transcripts for gene therapy for HPV-positive
      cervical cancers. METHODS: Via a recombinant adenoviral vector, Ad5CMV-HPV 16 AS,
      we introduced the antisense RNA transcripts of the E6 and E7 genes of HPV type 16
      into human cervical cancer SiHa cells harboring HPV 16. We then analyzed the
      effects of expression of these genes on cell and tumor growth. RESULTS: HPV 16
      E6/E7 antisense RNA was detected for 14 days in Ad5CMV-HPV 16 AS-infected cells.
      After infection, E6 and E7 protein expression was suppressed, and p53 and Rb
      protein expression increased. The Ad5CMV-HPV 16 AS-infected cells underwent
      apoptosis in vitro and in vivo. Cell growth and tumorigenicity were greatly
      suppressed. Ad5CMV-HPV 16 AS treatment significantly reduced the volumes of
      established subcutaneous tumors. CONCLUSION: Transfection of cervical cancer
      cells with HPV 16 E6/E7 antisense RNA in a form such as Ad5CMV-HPV 16 AS might be
      a potentially useful approach to the therapy of HPV 16-positive cervical cancer.

PMID- 16908055
TI  - Dehydroepiandrosterone sulfate, cortisol, mood state and smoking cessation:
      relationship to relapse status at 4-week follow-up.
AB  - It has been hypothesized that increased baseline dehydroepiandrosterone sulfate
      (DHEAS) levels may act as a natural antidepressant to attenuate negative affect
      during cocaine withdrawal and abstinence, decreasing the probability of relapse.
      The current study extends this model to assess factors related to risk of relapse
      in a sample of 68 nicotine dependent participants. Repeated measures ANOVAs were
      used to examine mood state, salivary DHEAS and cortisol levels across three
      assessment periods in participants who had relapsed over a 4-week follow-up
      period (n=51, 23 women) compared to those who maintained abstinence (n=17, 8
      women). Total scores on the Profile of Mood States differed between those who had
      relapsed and those who maintained abstinence (p=0.008). However, DHEAS and
      cortisol levels, as well as the ratio of cortisol to DHEAS, did not differ
      significantly between groups. These findings suggest that, although DHEAS-related
      enhancement of resiliency to withdrawal may occur, the extent of this protective
      effect may be modulated by additional factors that warrant further research.

PMID- 16908057
TI  - A stage of change approach to reducing occupational ill health.
AB  - OBJECTIVE: Interventions targeted by stage of change have been shown to improve
      the efficacy of public health promotion initiatives in areas such as smoking
      cessation, alcohol reduction, and mammography screening. Targeted interventions
      are designed to tackle the key attitudes, beliefs, and intentions that underpin
      an individual's health-related behavior. Work-related ill health is an
      increasingly serious issue, the most common cause of which in both the UK and the
      US is musculoskeletal disorders. This study examined whether the stage approach
      could be applied to workplace interventions aimed at improving occupational
      health. METHOD: A total of 24 multi-component occupational interventions aimed at
      reducing musculoskeletal disorders were monitored over a period of 4-6 months. In
      half of these cases, approaches were targeted according to workers' stage of
      change. RESULTS: Targeted interventions were found to be significantly more
      effective in promoting risk awareness and desired behavior change among workers.
      Significant reductions were also found in self-reported musculoskeletal
      discomfort among workers having received targeted interventions. No significant
      differences were found in self-reported musculoskeletal discomfort among workers
      following standard interventions. CONCLUSION: Stage-matched approaches may offer
      scope for substantially improving the efficacy of occupational health and safety
      interventions by increasing the uptake, implementation, and maintenance of risk
      reducing measures.

PMID- 16908056
TI  - National Cholesterol Education Program risk assessment and potential for risk
      misclassification.
AB  - BACKGROUND: The National Cholesterol Education Program Adult Treatment Panel
      report from 2001 (ATP III) recommends clinicians calculate 10-year coronary risk
      using multivariable methods only for adults with 2 or more risk factors. We aimed
      to determine who would be falsely classified as low risk using this approach.
      METHODS: We studied 4097 adults aged 20 to 79 years without diagnosed
      cardiovascular disease or diabetes from the National Health and Nutrition
      Examination Survey from 1999 to 2002. We determined the proportion with fewer
      than 2 risk factors who nonetheless had estimated 10-year risk of cardiac death
      or myocardial infarction > or =10% using multivariable methods. RESULTS: Among
      persons with fewer than 2 risk factors, 5.3% (95% confidence interval 4.7 to
      6.1%), had a 10-year risk > or =10% using the Framingham Risk Score and would be
      misclassified using the risk factor counting method (this corresponds to
      approximately 5,640,000 U.S. adults). Compared to individuals whose
      classification was unchanged, those misclassified as low risk were older
      (P<0.001) and more likely male (85.5% vs. 41.2%, P<0.001). CONCLUSIONS: Relying
      on the ATP III risk factor counting method rather than determining risk using
      multivariable methods in all patients resulted in misclassifiying as low risk
      over 5 million adults with at least moderately high risk of coronary heart
      disease, most of whom are middle-aged and older men.

PMID- 16908058
TI  - Hemispheric differences in strong versus weak semantic priming: evidence from
      event-related brain potentials.
AB  - GOALS: Research with lateralized word presentation has suggested that strong
      ("close") and weak ("remote") semantic associates are processed differently in
      the left and right cerebral hemispheres [e.g., Beeman, M. j., & Chiarello, C.
      (1998). Complementary right- and left-hemisphere language comprehension. Current
      Directions in Psychological Science, 7(1), 2-8]. Recently, this hypothesis has
      been challenged [Coney, J. (2002). The effect of associative strength on priming
      in the cerebral hemispheres. Brain and Cognition, 50(2), 234-241]. We predicted
      that foveal presentation of strong and weak associates would elicit different
      patterns of hemispheric activity, as indexed by high-density event-related brain
      potentials (ERPs), and that source localization of the scalp potentials would
      help clarify the nature of hemispheric contributions to semantic organization.
      METHODS: 128-channel ERPs were recorded in two experiments as subjects performed
      a lexical decision task. Word trials were equally divided into strongly related,
      weakly related, and unrelated word pairs. All words were foveally presented. SOA
      was 800 ms in Experiment 1, and 200 ms in Experiment 2. RESULTS: Topographic
      analyses revealed medial frontal (MFN) and parietal (N400/LPC) effects for both
      strong and weak associates. Between approximately 450 and 550 ms, the magnitude
      of the N400/LPC effect indicated priming for both strong and weak associates over
      left parietal sites, while priming over right parietal sites was restricted to
      strongly related word pairs. During this interval, spatiotemporal source modeling
      showed that these scalp effects were best accounted for by ipsilateral sources in
      the medial temporal lobe. The observed pattern of asymmetries for strong versus
      weak associates is not consistent with certain proposals regarding the
      complementarity of right- and left-hemisphere contributions to semantics. It is,
      however, consistent with findings from visual half-field studies (Hasbrooke and
      Chiarello, 1998). We discuss the relevance of these results for theories of
      hemispheric asymmetry and meta-control in lexical semantic access.

PMID- 16908059
TI  - Influence of the bonder on the adhesion of porcelain to machined titanium as
      determined by the strain energy release rate.
AB  - OBJECTIVE: To determine the adhesion at the titanium-porcelain interface using a
      fracture mechanics approach, and to investigate the bonding mechanism using SEM.
      METHODS: Specimens of five different titanium-porcelain and one base metal
      porcelain bonding systems were prepared for a four-point bending interfacial
      delaminating test on a universal testing machine. The pre-cracked specimen was
      subjected to load and the strain energy release rate (G, J/m(2)) was calculated
      from the critical load to induce stable crack extension in each system. The
      interface for the various materials was investigated in an SEM and compared.
      RESULTS: The titanium-porcelain with Gold Bonder showed the highest G-value
      (72.39+/-13.21J/m(2)) among the groups whilst titanium-porcelain with cross-cut
      bur preparation showed the lowest (5.78+/-1.39J/m(2)). The former was
      significantly higher than that of Wiron 99 (base-metal, BEGO, Germany) porcelain
      (40.01+/-6.67J/m(2)), a clinically accepted bonding system for many years. The G
      values of porcelain fused to titanium-Rocatec, titanium-sandblasted and/or
      titanium-GC-Bonder were 10.81+/-1.49, 12.64+/-3.01 and 35.74+/-5.20J/m(2),
      respectively. SEM images of the interface fracture crack path for the different
      bonders enabled the mechanisms responsible for the differences in strain energy
      release rates to be appreciated. CONCLUSION: The strain energy release rate (G)
      of titanium-porcelain with a Gold Bonder interface layer was highest among the
      five different systems.

PMID- 16908060
TI  - The effect of gelatin-chondroitin sulfate-hyaluronic acid skin substitute on
      wound healing in SCID mice.
AB  - Tissue-engineered skin substitutes provided a feasibility to overcome the
      shortage of skin autograft by culturing keratinocytes and dermal fibroblasts in
      vitro. In this study, we applied bi-layer gelatin-chondrointin-6-sulfate
      hyaluronic acid (gelatin-C6S-HA) biomatrices onto the severe combined
      immunodeficiency (SCID) mice to evaluate its effect on promoting wound healing.
      Human foreskin keratinocytes and dermal fibroblasts were cultured with
      reconstructed skin equivalent (rSE) for 7 days. The rSE was then grafted to the
      dorsum of SCID mice to evaluate its biocompatibility by histologic and
      immunohistochemistry analysis. The results showed that human epidermis were well
      developed with the expression of differentiated markers and basement membrane
      specific proteins at 4 weeks. After implantation, the percentages of skin graft
      take were satisfactory, while cell-seeded group was better than non-cell-seeded
      one. The basement membrane proteins including laminin, type IV collagen, type VII
      collagen, integrin alpha6, and integrin beta4 were all detected at the dermal
      epidermal junction, which showed a continuous structure in the 4 weeks after
      grafting. This bi-layer gelatin-C6S-HA skin substitute not only has positive
      effect on promoting wound healing, but also has high rate of graft take. This rSE
      would have the potential to be applied on the extensively and deeply burned
      patients who suffer from severe skin defect in the near future.

PMID- 16908061
TI  - Cell culture modifies Ca2+ signaling during excitation-contraction coupling in
      neonate cardiac myocytes.
AB  - In heart, the excitation-contraction coupling (ECC) mechanism changes during
      development. Primary cell culture has been used to study Ca(2+) signaling in
      newborn (NB) rat heart. In this work, the effects of cell culture on the action
      potential (AP) and ECC Ca(2+) signaling during development were investigated.
      Specifically, AP, Ca(2+) currents (I(Ca)), and ryanodine receptor (RyR)
      properties (i.e. density, distribution, and contribution to Ca(2+) transients and
      Ca(2+) sparks) were defined in cultured myocytes (CM) from 0-day-old NB rat at
      different times in culture (1-4 days). Compared with acutely dissociated myocytes
      (ADM) from NB of equivalent ages (1-4 days), CM showed lower RyR density (50% at
      1 day, 25% at 4 days), but larger RyR contribution to the Ca(2+) transient (25%
      at 1 day, 57% at 4 days). Additionally, Ca(2+) sparks were larger, longer, wider,
      and more frequent in CM than in ADM. RyR cellular distribution also showed
      different arrangement. While in CM, RyRs were located peripherally, in ADM of
      equivalent ages a sarcomeric arrangement was predominant. Finally, CM showed a
      two-fold increase in sarcolemmal Ca(2+) entry during the AP. These results
      indicated that primary culture is a feasible model to study Ca(2+) signaling in
      heart; however, it does not precisely reproduce what occurs in ECC during
      development.

PMID- 16908062
TI  - DNA replication in phage P4: characterization of replicon II.
AB  - The genetic element P4 propagates in its host Escherichia coli both as a
      satellite phage and as a plasmid. Two partially overlapping replicons coexist,
      namely replicon I and replicon II. The former is composed of two sites, ori1 and
      crr, and depends on P4 alpha gene product for replication. The P4 alpha protein
      has primase and helicase activities, and binds specifically to both ori1 and crr.
      Replicon II is composed of two sites, ori2 and crr, and its replication also
      depends on P4 alpha primase and helicase activities. In replicon II, the alpha
      protein binds only crr. Here we show that for replicon II the relative
      orientation of ori2 and crr is essential for replication to occur. Furthermore we
      delimit ori2 to a 22 bp region (6234-6255), internal to the alpha gene,
      sufficient for replicon II replication. We mutagenized this region and identified
      two mutants, which carry one and two base substitutions, respectively, that
      prevent replicon II replication. In electrophoretic mobility shift experiments of
      ori2, ori1, and crr DNA fragments with E. coli extracts, ori2 was not shifted,
      whereas both ori1 and crr were specifically bound, suggesting that other host
      protein(s), beside P4 alpha, are able to bind to these cis essential regions.
      Apparently, no binding to ori2 could be identified, thus suggesting that neither
      alpha nor other bacterial proteins specifically bind to this region.

PMID- 16908063
TI  - Remobilization and bioavailability of cadmium from historically contaminated
      sediments: influence of bioturbation by tubificids.
AB  - The effects of bioturbation by tubificids on cadmium (Cd) remobilization and
      bioavailability from sediment were studied throughout two experiments. With
      bioturbation, particulate Cd was transitorily released into the overlying water,
      in correlation with sediment resuspension (maximum of 6.1+/-0.1 microg L(-1)
      after 6 days). Cd bioaccumulation by the bivalve Corbicula fluminea was very
      limited (maximum of 1.73+/-0.34 microg g(-1), dw), and independent of the algae
      diet. In contrast, without bioturbation, the release of dissolved Cd increased
      with the duration of the experiments (maximum of 9.9+/-0.8 microg L(-1) after 36
      days). Cd bioaccumulation by C. fluminea varied according to their diet: low
      bioaccumulation when no algae were added (2.18+/-0.29 microg g(-1), dw), higher
      bioaccumulation when algae were added throughout the experiment (8.52+/-1.61
      microg g(-1), dw), and the highest bioaccumulation when algae were added only
      during the last 10 days of the experiment (19.66+/-4.63 microg g(-1), dw).

PMID- 16908064
TI  - Woman, alcohol and environment: Emerging risks for health.
AB  - Alcohol drinking is one of the most relevant problems in Western Countries but
      the negative effects of alcohol misuse are often neglected or underestimated with
      serious consequences for public health. Over the last few years a rapid growth in
      the number of drinking females and the decrease of their age of first use, have
      increased the health risk for women and their offspring. Moreover, modern
      environments facilitate pollutants exposure, further escalating the health risks
      due to lifestyle habits. This review takes into account the peculiarities of
      alcohol effects on female health and the risks of teratogenic effects. The
      possible interaction between alcohol and pollutants exposure is also discussed.
      The role of biomarkers against alcohol-related damage is presented as an
      invaluable clinical tool, including early intervention, treatment monitoring and,
      above all, prevention of prenatal non-reversible damage. Recent alcohol studies
      show the greater severity of alcohol damage in female subjects and the need of
      gender-targeted intervention.

PMID- 16908065
TI  - Metabolic and genetic factors contributing to alcohol induced effects and fetal
      alcohol syndrome.
AB  - Alcohol-related damages on newborns and infants include a wide variety of
      complications from facial anomalies to neurodevelopmental delay, known as fetal
      alcohol syndrome (FAS). However, only less than 10% of women drinking alcohol
      during pregnancy have children with FAS. Understanding the risk factors
      increasing the probability for newborn exposed in utero to alcohol to develop FAS
      is therefore a key issue. The involvement of genetics as a one risk factor in FAS
      has been suggested by animal models and by molecular epidemiological studies on
      different populations, bearing allelic variants for those enzymes, such as ADH e
      CYP2E1, involved in ethanol metabolism. Indeed, one of the major factors
      determining the peak blood alcohol exposure to the fetus is the metabolic
      activity of the mother, in addition to placental and fetal metabolism,
      explaining, at least partially, the risk of FAS. The different rates of ethanol
      metabolism may be the result of genetic polymorphisms, the most relevant of which
      have been described in the paper.

PMID- 16908066
TI  - The importance of alcohol misuse, malnutrition and genetic susceptibility on
      brain growth and plasticity.
AB  - The "dyad: alcoholic mother and foetus" is a very complex entity in which several
      elements such as genes, metabolism, diet, drugs and social habits play a role at
      different stages in the development of the fetal brain damage. The literature on
      the effects of alcohol consumption on the developing brain is extensive but very
      few evidences have been reported regarding the combined neurotoxic effects of
      poor nutrition and alcohol consumption. The consequences of ethanol intake alone
      or combined with poor maternal nutrition appear to be severe and life-long.
      Alcohol exerts its neurotoxic effects on the developing brain directly by acting
      on fetal brain tissues, and indirectly either by interfering with placental
      physiology or by impairing the mother's physiology. Alcohol misuse in pregnancy
      is also frequently associated with other conditions that can potentially increase
      the brain damage such as poor nutrition and smoking. This article reviews the
      effects of poor nutrition and alcohol misuse during pregnancy on the development
      of the fetal brain and discusses the cumulative effects of these two
      environmental factors and their interaction with maternal and fetal genetic make
      ups.

PMID- 16908068
TI  - In vivo immunostimulatory effects of CpG ODN in newborn piglets.
AB  - The in vivo immunoadjuvant effects of CpG oligodeoxynucleotides (CpG ODN) have
      been studied extensively in mice and relatively fewer studies have been done in
      other species. But so far, the innate immunostimulatory effects of CpG ODN have
      been demonstrated just in mouse, monkey, sheep and chicken in some reports. The
      purpose of this study is to determine the potential effects of CpG ODN in newborn
      piglets. The proportion of CD4(+), CD8(+) T lymphocytes subpopulations and the
      major histocompability complex (MHC-II) antigen expression of peripheral blood
      mononuclear cells (PBMCs) and IFN-gamma in serum were tested at various time
      points. The results suggested that, the CD4(+)/CD8(+) ratio decreased over time
      in piglets inoculated with phosphate buffer saline (PBS) alone, however, it was
      stable in CpG ODN-inoculated piglets; the use of CpG ODN can prevent effectively
      the reduction of the proportion of CD4(+) T lymphocytes. The MHC-II antigen
      expression and IFN-gamma level of CpG ODN-injected piglets were significantly
      higher than those of PBS-injected piglets. The ODN-induced responses were
      stronger in animals injected with CpG ODN formulated in 30% emulsigen than in
      PBS. The innate immunostimulatory activity of CpG ODN appeared to be in dose
      dependent manner. These in vivo data demonstrate for the first time that CpG ODN
      can stimulate innate immune system in newborn piglets.

PMID- 16908067
TI  - Complement proteins C1q and MBL are pattern recognition molecules that signal
      immediate and long-term protective immune functions.
AB  - C1q and mannose binding lectin, members of the "defense collagen" family, are
      pattern recognition molecules that can trigger rapid enhanced phagocytosis
      resulting in efficient containment of pathogens or clearance of cellular debris,
      apoptotic cells and immune complexes. In addition, interaction of C1q and mannose
      binding lectin with the phagocyte alters subsequent phagocyte cytokine synthesis,
      and thus may have important implications in directing acute inflammation as well
      as long-term protective immunity. The importance of the role of defense collagens
      in phagocytosis of apoptotic cells is highlighted by studies in vivo of mice
      deficient in C1q, pulmonary surfactant D and mannose binding lectin in which
      there is delayed clearance of apoptotic cells. Indeed, deficiency of C1q is a
      risk factor for the development of autoimmunity in both humans and mice,
      consistent with the hypothesis that inefficient clearance of apoptotic cells
      results in release of autoantigens and contributes to the pathology associated
      with autoimmune diseases such as systemic lupus erythematosus. Further
      understanding of the importance of C1q and mannose binding lectin in the
      clearance of apoptotic cells and regulation of cytokine synthesis and
      identification of the receptors implicated in mediating these processes should
      provide novel targets for therapeutic intervention in the control and
      manipulation of the immune response in terms of both host defense against
      infectious disease and tissue repair and remodeling.

PMID- 16908069
TI  - Stabilization of type I collagen against collagenases (type I) and thermal
      degradation using iron complex.
AB  - The widespread application of collagen as a biomaterial warrants research in
      understanding the stabilization of the same. In this study, interaction of iron
      tetrakis (hydroxymethyl) phosphonium (THP) complex with type I collagen has been
      investigated. DSC and hydrothermal measurement studies reveal that the shrinkage
      temperature of iron-THP treated rat tail tendon (RTT) collagen is 33 degrees C
      higher than that of native RTT collagen. Fe-THP complex also brings about high
      degree of enzymatic stability to type I collagen. The effect of Fe-THP on the
      conformation of collagen was studied using circular dichroism and it was found
      that no major alterations in the triple helical structure of collagen occur on
      treatment with Fe-THP. It is observed from viscosity experiment results that
      though Fe-THP complex is able to bring about long range ordering of collagen, as
      evident from the thermal and enzymatic stability imparted to collagen, this
      ordering does not lead to any aggregation of collagen. Since THPS is reducing in
      nature, it is expected to keep iron in the +2 state and if THP chelates to
      Fe(II), the hydrolytic behavior of iron can also be controlled.

PMID- 16908070
TI  - Synergistic and additive antiproliferative effects on human leukemia cell lines
      induced by combining acetylenehexacarbonyldicobalt complexes with the tyrosine
      kinase inhibitor imatinib.
AB  - The tyrosine kinase inhibitor imatinib is successfully used in the treatment of
      chronic myeloid leukemia, but the occurrence of resistance phenomena can
      significantly limit therapeutic impact. Imatinib shows synergistic effects with
      cisplatin, suggesting that the coadministration of different cytostatics might
      reestablish the efficacy of treatment. We recently demonstrated that cobalt
      alkyne (or acetylenehexacarbonyldicobalt) complexes induce antiproliferative
      activity in human leukemia and lymphoma cells. The present study evaluates the
      effects of cobalt alkyne compounds containing propargylic acid esters on human
      acute (HL-60) and chronic myeloid (LAMA-84 and CML-T1) leukemia cell lines. The
      cell growth inhibitory activities (IC(50) values of 9.5 microM and higher) and
      induction of apoptosis (maximum 5.5-fold increase of single-stranded DNA at a
      drug concentration of 50 microM) achieved with the single agents were moderate.
      Interestingly, suboptimal concentrations of the cobalt complexes (10 microM)
      together with imatinib (0.1 microM), when coadministered, showed an additive or
      synergistic effect on cellular proliferation inhibition. The most promising
      results were obtained with complexes containing ligands derived from the
      nonsteroidal antiinflammatory drugs acetylsalicylic acid and naproxene.

PMID- 16908071
TI  - Identification of a c-kit exon 8 internal tandem duplication in a feline mast
      cell tumor case and its favorable response to the tyrosine kinase inhibitor
      imatinib mesylate.
AB  - The gain-of-function mutations within c-kit, a protooncogene encoding KIT, induce
      constitutive ligand-independent kinase activation and are important for the
      pathogenesis of mast cell proliferative disease in humans as well as in dogs.
      Despite the clinical importance of feline mast cell tumors, no mutation has been
      shown within the c-kit gene in cats. In the present report, we analyzed the c-kit
      nucleotide sequence in the case of a cat that showed systemic mastocytosis and
      mastocytemia. Within the c-kit cDNA prepared from the malignant mast cells, we
      identified an 12-bp internal tandem duplication at the region corresponding to
      exon 8, resulting in a four amino acid insertion between residues Thr418 and
      His419 within the fifth immunoglobulin-like domain of KIT. The cat underwent
      therapy with the kinase inhibitor imatinib mesylate (Gleevec) at a dose of
      10mg/kg. The tumor masses greatly responded and were undetectable after 5 weeks
      of treatment. Correspondingly, the number of mast cells in the peripheral blood
      was markedly reduced. It is, therefore, considered that the internal tandem
      duplication within the domain contributes to the neoplastic transformation of
      mast cells in the cat by increasing KIT phosphorylation.

PMID- 16908072
TI  - Single-cell analysis divides bovine monocyte-derived dendritic cells into subsets
      expressing either high or low levels of inducible nitric oxide synthase.
AB  - Dendritic cells (DC) are important cells at the interface between innate and
      adaptive immunity. DC have a key role in antigen processing and presentation to T
      cells. Effector functions of DC related to innate immunity have not been explored
      extensively. We show that bovine monocyte-derived DC (mDC) express inducible
      nitric oxide synthase (iNOS) mRNA and protein and produce NO upon triggering with
      interferon-gamma (IFN-gamma) and heat-killed Listeria monocytogenes (HKLM). An
      immunocytochemical analysis revealed that a sizeable subset (20-60%) copiously
      expresses iNOS (iNOShi) upon IFN-gamma/HKLM triggering, whereas the other subset
      expressed low levels of iNOS (iNOSlo). Monocyte-derived macrophages (mMphi) are
      more homogeneous with regard to iNOS expression. The number of cells within the
      iNOSlo mDC subset is considerably larger than the number of dead cells or cells
      unresponsive to IFN-gamma/HKLM. The large majority of cells translocated p65 to
      the nucleus upon triggering by IFN-gamma/HKLM. A contamination of mDC with iNOS
      expressing mMphi was excluded as follows. (i) Cell surface marker analysis
      suggested that mDC were relatively homogeneous, and no evidence for a
      contaminating subset expressing macrophage markers (e.g. high levels of CD14) was
      obtained. (ii) iNOS expression was stronger in iNOShi mDC than in mMphi. The use
      of maturation-promoting stimuli revealed only subtle phenotypic differences
      between immature and mature DC in cattle. Nevertheless, these stimuli promoted
      development of considerably fewer iNOShi mDC upon triggering with IFN-gamma/HKLM.
      Immunocytochemical results showed that although a significant proportion of cells
      expressed iNOS only or TNF only upon triggering with IFN-gamma/HKLM, a
      significant number of cells expressed both iNOS and TNF, suggesting that TNF and
      iNOS producing (TIP) DC are present within bovine mDC populations obtained in
      vitro.

PMID- 16908073
TI  - Is there a role for the otolaryngologist in PFAPA syndrome? A systematic review.
AB  - AIMS: To define the role of medical or surgical treatment in patients with
      periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA
      syndrome). METHODS: A Medline search was performed using the terms PFAPA,
      periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis, treatment. A
      systematic review of the English literature was performed. Papers on pyrexia of
      unknown origin in the pediatric population were excluded; this was because the
      clinical entities included in the differential diagnosis of pyrexia of unknown
      origin share many clinical characteristics with PFAPA, and may be ill defined.
      RESULTS: Twenty-seven papers have been published since 1989, of which 20 were in
      English language. There were five single case reports and two papers involving
      two patients each. There were 6 retrospective reviews of case notes, involving 5
      94 patients over a 3-10 year review period. Given that current evidence on the
      effectiveness of tonsillectomy in PFAPA is extremely weak (level of evidence V),
      tonsillectomy should not be performed. CONCLUSIONS: PFAPA usually resolves
      without any long-term adverse effect, and as such, there is no role for
      tonsillectomy in these patients.

PMID- 16908074
TI  - Immune cell signaling: a novel mechanistic model reveals new therapeutic targets.
AB  - Multichain immune recognition receptors (MIRRs) represent a family of surface
      receptors that is expressed on different cells and that transduces extracellular
      signals, leading to many biological responses. The most intriguing common
      structural feature of MIRR family members is that the extracellular recognition
      domains and the intracellular signaling domains are located on separate subunits.
      It is not clear how extracellular ligand binding triggers MIRRs and initiates
      intracellular signal-transduction processes. In this article, I suggest that the
      structural similarity of the MIRRs provides the basis for the similarity in the
      mechanisms of MIRR-mediated transmembrane signaling. This hypothesis assumes that
      the therapeutic strategies learned from a novel mechanistic model of MIRR
      mediated signal transduction, the signaling chain homo-oligomerization model, are
      generalized for this entire family and have important implications for the
      treatment of many disorders that are mediated by immune cells, including HIV.

PMID- 16908075
TI  - Opioids and motor complications in Parkinson's disease.
AB  - The long-term treatment of Parkinson's disease with L-dopa is often associated
      with the appearance of involuntary movements called L-dopa-induced dyskinesias.
      These debilitating side-effects are thought to result from an aberrant form of
      plasticity triggered by a combination of factors related to dopamine denervation
      and repeated L-dopa administration. In animal models of Parkinson's disease,
      dopamine denervation and repeated L-dopa administration are associated with an
      enhancement of opioid transmission in the basal ganglia. The exact role of this
      increased opioid activity is still under debate. It has been proposed that some
      of the changes in opioid transmission are directly involved in the genesis of L
      dopa-induced dyskinesias. In this article, we suggest that changes in opioid
      transmission in the basal ganglia in response to denervation and repeated L-dopa
      therapy are, instead, part of compensatory mechanisms to prevent motor
      complications. Initially, these compensatory mechanisms might be sufficient to
      attenuate the parkinsonian syndrome and delay the appearance of involuntary
      movements. But with the progression of the disease and repeated exposure to L
      dopa, these mechanisms eventually fail. These new insights could contribute to
      better understanding of the motor complications in Parkinson's disease and lead
      to the development or improvement of pharmacological strategies to prevent or
      reduce L-dopa-induced dyskinesias.

PMID- 16908076
TI  - Evaluation of a new fourth generation enzyme-linked immunosorbent assay, the LG
      HIV Ag-Ab Plus, with a combined HIV p24 antigen and anti-HIV-1/2/O screening
      test.
AB  - The LG HIV Ag-Ab Plus, a new fourth generation diagnostic assay for HIV
      infection, was evaluated in comparison to the Enzygnost HIV Integral, an
      established fourth generation HIV assay. The LG assay showed 100% sensitivity
      with 109 samples with anti-HIV-1, anti-HIV-2 or anti-HIV-1 group O reactivity. It
      also detected correctly all 51 positives on three BBI performance panels,
      slightly outperforming the Enzygnost HIV Integral, which detected 50. The
      specificity of the LG HIV Ag-Ab Plus was 99.9% with 999 sera from healthy blood
      donors, which was slightly inferior to the performance of the Enzygnost HIV
      Integral, which had 100% specificity. The LG assay showed 100% specificity with
      81 specimens with underlying diseases including hepatitis B, demonstrating a low
      risk of cross-reactivity with other infections. The reduction of the diagnostic
      window by the LG HIV Ag-Ab Plus, compared to a third generation HIV assay, was
      6.3 days. The LG assay also showed sufficiently high intra-person and inter
      person reproducibility. The overall performance of this new fourth generation HIV
      assay was adequate for screening and diagnosis of HIV infection.

PMID- 16908077
TI  - Effects of fixative type and fixation time on the detection of Maedi Visna virus
      by PCR and immunohistochemistry in paraffin-embedded ovine lung samples.
AB  - In doubtful cases, the histopathological diagnosis of lesions induced by Maedi
      Visna virus (MVV), a chronic multisystemic lentiviral disease of sheep, needs to
      be confirmed by the demonstration of MVV in the tissues. The influence of
      fixatives and the duration of fixation on the detection of MVV by
      immunohistochemistry (IHC) and PCR in paraffin-embedded tissues was assessed in
      lung samples with lesions in different degree, from five sheep serologically
      positive. Samples were fixed in 10% neutral buffered formalin (NBF), Bouin's
      solution (BS) and a zinc salts-based fixative (ZSF), for different periods of
      time between 24 h and 30 days. The three fixatives preserved the morphology of
      the tissues, although in ZSF-fixed samples an increase in the number of
      desquamated cells was seen in the alveoli. Tissues showed a similar degree of
      immunolabelling, irrespective of the duration of fixation using ZSF and NBF
      fixatives. MVV nucleic acids could be detected in samples fixed up to 14 days in
      NBF and 30 days in ZSF. However, in BS fixed tissues, immunostaining was weak and
      non-specific signals were observed after 4 days of fixation. Amplification of
      proviral DNA could not be obtained by PCR in these samples. IHC detected viral
      antigens in all sheep whereas one sheep with mild lesions was always negative by
      PCR.

PMID- 16908078
TI  - Differential gene expression in the ookinete stage of the malaria parasite
      Plasmodium berghei.
AB  - Plasmodium, the malaria parasite, undergoes a complex developmental program in
      its mosquito vector. The ookinete is the parasite form which invades the mosquito
      midgut and is an important stage for genetic mixing. To identify genes expressed
      during ookinete development and mosquito midgut invasion, purified zygotes and
      ookinetes of the rodent parasite Plasmodium berghei were used to construct a
      suppression subtractive hybridization cDNA library, enriched in sequences
      expressed in the ookinete stage. In addition to four genes coding for previously
      described major ookinete-secreted proteins, we isolated ookinete-expressed
      sequences representing 18 predicted genes. Their gene products include proteins
      involved in signal transduction and regulatory processes. For six of these genes
      our analysis provides the first evidence for expression in the ookinete stage. A
      majority of the genes are not expressed in the zygote, the preceding
      developmental stage. Furthermore, four of the genes are also transcribed in
      sporozoites, and one of these in merozoites, suggesting that they code for
      proteins with a function common to Plasmodium invasive stages.

PMID- 16908079
TI  - DPPIV inhibitors extend GLP-2 mediated tumour promoting effects on intestinal
      cancer cells.
AB  - BACKGROUND: The glucagon-like peptides-1 and -2 (GLP-1 and -2) are co-secreted
      after food intake from intestinal L cells. Since both peptides are rapidly
      degraded by dipeptidyl peptidase-IV (DPPIV), research is focused on the
      development of DPPIV inhibitors or DPPIV resistant. AIMS: In this study we
      investigated, whether the inhibition of DPPIV activity and the resulting
      increased half-life of DPPIV substrates may influence cancer development and
      progression. METHODS: We examined proliferation and migratory activity of two
      human colon cancer cell lines (SW480, HT29) after stimulation with GLP-2 in
      combination with or without DPPIV inhibitors. RESULTS: Migratory activity was
      increased by 25% from 20% matrix induced activity to a maximum of 45% (100 nM GLP
      2). In cells expressing CD26, migration was prolonged by addition of DPPIV
      inhibitors in a concentration dependent manner. After treatment with GLP-2
      doubling time decreased from 2.4 to 1.5 days - and addition of DPPIV inhibitors
      enhanced the effect of GLP-2. CONCLUSIONS: The use of DPPIV inhibitors together
      with GLP-2 led to increased proliferation as well as elevated migratory activity.
      Therefore, the use of DPPIV inhibitors could increase the risk of promoting an
      already existing intestinal tumour and may support the potential of colon cancer
      cells to metastasize.

PMID- 16908080
TI  - Sirolimus eluting stent fracture following angioplasty of diffuse in-stent
      restenosis in the right coronary artery.

PMID- 16908081
TI  - Is left coronary system more susceptible to atherosclerosis than right? A
      pathophysiological insight.
AB  - On the basis of pathological, angiographical, intravascular ultrasound and
      computed tomography data coronary atherosclerosis appears to be more prevalent in
      the left coronary arterial system compared to the right. However, the
      pathophysiological mechanisms implicated in this discrepancy largely remain
      uncertain. The hemodynamic or anatomical differences between the right and left
      coronary artery might play a key role. Physiologically, the right coronary flow
      is more uniform during the cardiac cycle compared to the left, which experiences
      a remarkable systolic decline accompanied by a significant diastolic increment.
      Thus, the oscillatory shear stress, that constitutes a proved atherogenic factor,
      is more intense in regions with disturbed flow in the left coronary system.
      Likewise, the wall stress is more oscillatory during the cardiac cycle in the
      left coronary artery. On top of that, several differences regarding the
      anatomical configuration (3D geometry, branching) and the phasic motion between
      the right and the left arterial system appear to play a critical role in the
      modulation of the local atherogenic environment. Therefore, it could be assumed
      that the flow characteristics along with the geometrical and phasic motion
      patterns generate an intense oscillation of the imposed to the arterial wall
      stresses, especially in the left coronary artery. Over the long-term, these
      augmented oscillatory stresses, in combination with the effect of systemic risk
      factors, might modulate a more atherogenic environment in the atherosclerosis
      prone regions of the left coronary system.

PMID- 16908082
TI  - MDCT evaluation of a double outlet right ventricle after the Rastelli procedure.

PMID- 16908083
TI  - Predictability and predictiveness in health care spending.
AB  - This paper re-examines the relation between the predictability of health care
      spending and incentives due to adverse selection. Within an explicit model of
      health plan decisions about service levels, we show that predictability (how well
      spending on certain services can be anticipated), predictiveness (how well the
      predicted levels of certain services contemporaneously co-vary with total health
      care spending), and demand responsiveness all matter for adverse selection
      incentives. The product of terms involving these three measures of
      predictability, predictiveness, and demand responsiveness define an empirical
      index of the direction and magnitude of selection incentives. We quantify the
      relative magnitude of adverse selection incentives bearing on various types of
      health care services in Medicare. Our results are consistent with other research
      on service-level selection. The index of incentives can readily be applied to
      data from other payers.

PMID- 16908084
TI  - Monocyte-derived macrophages from men and women with Type 2 diabetes mellitus
      differ in fatty acid composition compared with non-diabetic controls.
AB  - We examined whether macrophages from men and women with Type 2 diabetes mellitus
      (T2DM) exhibited differences in expression of key genes involved in fatty acid
      metabolism and in fatty acid composition compared with macrophages from non
      diabetic controls. Peripheral blood monocytes from subjects with T2DM (n=9) and
      non-diabetic controls (n=10) were differentiated into macrophages in 10%
      autologous serum and normal (5mM) or high (22mM) glucose. Levels of PPARalpha,
      PPARgamma, LXRalpha, SCD and ABCA1 mRNAs were similar in macrophages from
      subjects with T2DM and controls. At 5mM glucose, macrophage stearic acid (C18:0)
      was 12.6+/-1.0% of total fatty acids for T2DM compared with 18.1+/-2.0% for
      controls (p=0.03). Macrophage linoleic acid (C18:2) was 15.5+/-0.8% for T2DM and
      9.3+/-2.0% for controls (p=0.005). The ratio of macrophage stearic acid
      (C18:0)/oleic acid (C18:1) was 0.29 [0.25,0.48] for T2DM versus 0.54 [0.36,0.82]
      for controls (p=0.04). Compared with non-diabetic controls, macrophages from men
      and women with T2DM had significantly different fatty acid profiles consistent
      with increased stearoyl-CoA desaturase (SCD) activity and increased C18:2
      accumulation. This pattern of altered macrophage fatty acid composition may be
      relevant to diabetic atherogenesis.

PMID- 16908085
TI  - How far can we go with marginal donors?

PMID- 16908086
TI  - The risk of upcoding in casemix systems: a comparative study.
AB  - With the introduction of a diagnosis related group (DRG) classification system in
      the Netherlands in 2005 it has become relevant to investigate the risk of
      upcoding. The problem of upcoding in the US casemix system is substantial. In
      2004, the US Centres for Medicare and Medicaid estimated that the total number of
      improper Medicare payments for the Prospective Payment system for acute inpatient
      care (both short term and long term) amounted to US$ 4.8 billion (5.2%). By
      comparing the casemix systems in the US, Australian and Dutch healthcare systems,
      this article illustrates why certain casemix systems are more open to the risk of
      upcoding than other systems. This study identifies various market, control and
      casemix characteristics determining the weaknesses of a casemix reimbursement
      system to upcoding. It can be concluded that fewer opportunities for upcoding
      occur in casemix systems that do not allow for-profit ownership and in which the
      coder's salary does not depend on the outcome of the classification process. In
      addition, casemix systems in which the first point in time of registration is at
      the beginning of the care process and in which there are a limited number of
      occasions to alter the registration are less vulnerable to the risk of upcoding.
      Finally, the risk of upcoding is smaller in casemix systems that use
      classification criteria that are medically meaningful and aligned with clinical
      practice. Comparing the US, Australian and Dutch systems the following
      conclusions can be drawn. Given the combined occurrences of for-profit hospitals
      and the use of the secondary diagnosis criterion to classify DRGs, the US casemix
      system tends to be more open to upcoding than the Australian system. The strength
      of the Dutch system is related to the detailed classification scheme, using
      medically meaningful classification criteria. Nevertheless, the detailed
      classification scheme also causes a weakness, because of its increased complexity
      compared with the US and Australian system. It is recommended that researchers
      and policy makers carefully consider all relevant market, control and casemix
      characteristics when developing and restructuring casemix reimbursement systems.

PMID- 16908087
TI  - Switching trypanosome coats: what's in the wardrobe?
AB  - The African trypanosome Trypanosoma brucei is best known for its extraordinarily
      sophisticated antigenic variation of a protective variant surface glycoprotein
      (VSG) coat. T. brucei has >1000 VSG genes and pseudogenes, of which one is
      transcribed at a time from one of multiple telomeric VSG expression sites.
      Switching the active VSG gene can involve DNA rearrangements replacing the old
      VSG with a new one, or alternatively transcriptional control. The astonishing
      revelation from the T. brucei genome sequence is that <7% of the sequenced VSGs
      seem to have fully functional coding regions. This preponderance of pseudogenes
      in the VSG gene repertoire will necessitate a rethink of how antigenic variation
      in African trypanosomes operates.

PMID- 16908088
TI  - Charging it up: global analysis of protein phosphorylation.
AB  - Protein phosphorylation affects most, if not all, cellular activities in
      eukaryotes and is essential for cell proliferation and development. An estimated
      30% of cellular proteins are phosphorylated, representing the phosphoproteome,
      and phosphorylation can alter a protein's function, activity, localization and
      stability. Recent studies for large-scale identification of phosphosites using
      mass spectrometry are revealing the components of the phosphoproteome. The
      development of new tools, such as kinase assays using modified kinases or protein
      microarrays, enables rapid kinase substrate identification. The dynamics of
      specific phosphorylation events can now be monitored using mass spectrometry,
      single-cell analysis of flow cytometry, or fluorescent reporters. Together, these
      techniques are beginning to elucidate cellular processes and pathways regulated
      by phosphorylation, in addition to global regulatory networks.

PMID- 16908089
TI  - Genomics and conservation genetics.
AB  - In large part, the relevance of genetics to conservation rests on the premise
      that neutral marker variation in populations reflects levels of detrimental and
      adaptive genetic variation. Despite its prominence, this tenet has been difficult
      to evaluate, until now. As we discuss here, genome sequence information and new
      technological and bioinformatics platforms now enable comprehensive surveys of
      neutral variation and more direct inferences of detrimental and adaptive
      variation in species with sequenced genomes and in 'genome-enabled' endangered
      taxa. Moreover, conservation schemes could begin to consider specific
      pathological genetic variants. A new conservation genetic agenda would utilize
      data from enhanced surveys of genomic variation in endangered species to better
      manage functional genetic variation.

PMID- 16908090
TI  - The double burden on safety net providers: placing health disparities in the
      context of the privatization of health care in the US.
AB  - The US Institute of Medicine's (IOM) influential 2003 report has focused
      attention on disparities in treatment outcomes and health status for American
      minorities, zeroing in on the role of unconscious bias in the unequal clinical
      disposition of minority patients. In keeping with the IOM's focus, current
      examinations of health disparities in the US tend to explore bias in clinical
      decision-making to the neglect of the political economic trends that buffet
      health care safety net sites and create the need for financial shortcuts. This
      paper recontextualizes the study of health disparities in the US by placing it
      against the backdrop of private sector trends emphasizing fiscal austerity and
      increased workforce productivity in health care. The social science literature on
      workers in human service bureaucracies, only recently applied to health care
      workers, suggests that higher demands for system "accountability" and worker
      "efficiency" may encourage providers to take shortcuts by treating individuals as
      mass categories. This ethnography of a Latino mental health clinic in the
      Northwestern USA shows that new private-sector measures of "productivity" take a
      toll on both the Latina clinicians whose invisible work subsidizes the system as
      well as on particular categories of patients--the uninsured and immigrants with
      serious psychosocial issues. While clinicians attempt to buffer the impacts of
      such reforms on patients, they also resort to means to increase their
      productivity such as firing repeated no-show patients and denial of care to the
      uninsured. This study is relevant for the health care of the poor in all health
      care systems considering restructuring along managerial principles to increase
      system 'efficiencies.'

PMID- 16908091
TI  - The roles performed by peer educators during outreach among heroin addicts in
      India: ethnographic insights.
AB  - Peer-based outreach is a popular strategy in which former or current drug addicts
      are employed as peer educators to contact and educate out-of-treatment addicts.
      This study examines the interaction patterns that occur during outreach with
      particular regard to the roles that peer educators perform. Using ethnographic
      methods, it reports findings from a group of 'peer educators' and 'clients' from
      Yamuna Bazaar, New Delhi. In this context, peer educators assumed three roles
      that were co-constructed with clients: 'counsellor', 'doctor', and 'role model'.
      Analysis of these role-plays revealed three significant patterns. First, the
      performances involved a hierarchical structuring with the peer educator in an
      authority position in nearly all interactions. Second, the role-plays were fluid
      and evolving with peer educators often transitioning across roles during the same
      interaction. Lastly, role performances appeared to have an underlying role
      replication mechanism in which roles were learned by first playing the
      subordinate role (e.g. 'patient') and then performing the dominant role (e.g.
      'doctor') with another peer (e.g. new 'patient'). These findings provide insight
      into issues of empowerment, peer relationship dynamics, and social diffusion
      processes among drug-using communities, and peer-based situations more generally.

PMID- 16908092
TI  - Cloning and characterisation of natriuretic peptides from the venom glands of
      Australian elapids.
AB  - The venom from Australian elapid snakes contains a complex mixture of polypeptide
      toxins that adversely affect multiple homeostatic systems within their prey in a
      highly specific and targeted manner. Included in these toxin families are the
      recently described venom natriuretic peptides, which display similar structure
      and vasoactive functions to mammalian natriuretic peptides. This paper describes
      the identification and detailed comparative analysis of the cDNA transcripts
      coding for the mature natriuretic peptide from a total of nine Australian elapid
      snake species. Multiple isoforms were identified in a number of species and
      represent the first description of a natriuretic peptide from the venom gland for
      most of these snakes. Two distinct natriuretic peptide isoforms were selected
      from the common brown snake (Pseudonaja textilis), PtNP-a, and the mulga
      (Pseudechis australis), PaNP-c, for recombinant protein expression and functional
      analysis. Only one of these peptides, PtNP-a, displayed cGMP stimulation
      indicative of normal natriuretic peptide activity. Interestingly, both
      recombinant peptides demonstrated a dose-dependent inhibition of angiotensin
      converting enzyme (ACE) activity, which is predictive of the vasoactive effects
      of the toxin. The natriuretic peptides, however, did not possess any
      coagulopathic activity, nor did they inhibit or potentiate thrombin, adenosine
      diphosphate or arachidonic acid induced platelet aggregation. The data presented
      in this study represent a significant resource for understanding the role of
      various natriuretic peptides isoforms during the envenomation process by
      Australian elapid snakes.

PMID- 16908093
TI  - In-hospital cardiac resuscitation outside the ICU by nursing staff equipped with
      automated external defibrillators--the first 500 cases.
AB  - BACKGROUND: Since nursing staff in the hospital are frequently the first to
      witness a cardiac arrest, they may play a central role in the effective
      management of in-hospital cardiac arrest. In this retrospective study the first
      500 in-hospital cardiac arrests in non-monitored areas, which were treated
      initially by nursing staff equipped with automated external defibrillators (AEDs)
      are reported. METHODS AND RESULTS: Between April 2001 and December 2004, 500 in
      hospital cardiac arrest calls were made: there were false arrests in 61 patients,
      so a total of 439 patients (88%) were evaluated using the Utstein style of data
      collection. ROSC occurred in 256 patients (58%), 125 (28%) were discharged from
      hospital and 95 (22%) were still alive 6 months after discharge. Among the 73
      patients with VF/VT 63 (86%) had ROSC, 34 (47%) were discharged from hospital and
      28 (38%) were alive after 6 months. The chance of survival was not influenced by
      the time between the call of the arrest team and the 1st defibrillation but was
      slightly higher with physicians as in-hospital first responders (p=0.078). In
      contrast, 366 patients with non-VF/VT, 193 (53%) had ROSC, but only 91 (25%) were
      discharged from hospital and 67 (18%) were alive after 6 months. The risk of
      dying was significantly higher in patients with non-VF/VT (p<0.001), and there
      was a trend to a higher risk ratio in patients older than 65 years and in
      patients with non-witnessed cardiac arrest (p=0.056 and 0.079, respectively).
      CONCLUSION: This observational study supports the concept of hospital-wide first
      responder resuscitation performed by nursing staff before the arrival of the CPR
      team. Among these patients survival rate was higher in those with VF/VT
      defibrillated at an early stage. Consequently, it may be assumed that patients
      may die unnecessarily due to sudden cardiac arrest if proper in-hospital
      resuscitation programmes are not available.

PMID- 16908094
TI  - Consent in resuscitation trials: benefit or harm for patients and society?
AB  - CONTEXT: Research in an emergency setting is challenging because there may not be
      sufficient opportunity or time to obtain informed consent from the patient or
      their legally authorized representative. Such research can be conducted without
      prior consent if specific criteria are met. However consent is sometimes required
      for continued participation and may bias the results of the study. OBJECTIVE: To
      review regulations related to waiver of consent in emergency research, and
      evidence of whether such regulations introduce bias. RESULTS: Emergency research
      can be conducted without consent, either through community disclosure and
      consultation followed by patient or family notification and consent for continued
      participation after the intervention was applied, or under a minimal risk waiver.
      Review of the clinical record is necessary to determine important outcomes such
      as survival to discharge. If consent is required for this review but not granted,
      then these data are missing during analysis. If seriously ill or disadvantaged
      patients are less likely to assent, then investigators cannot determine reliably
      whether these vulnerable patients were harmed by the intervention. If missing
      data are different from complete data, then the analysis is susceptible to bias,
      and the conclusions could be misleading. Extrapolation from non-consent rates in
      resuscitation studies to results from the DAVID trial demonstrates that the rate
      of absence of data and information due to lack of assent can influence whether
      there is a significant difference between treatment groups (survival of control
      versus intervention: p=0.04 for complete data; p=0.08 for 10.8% lack of assent;
      p=0.40 for 19.7% lack of assent). CONCLUSIONS: Exception from consent for
      emergency research should extend to review of the hospital record as the standard
      in emergency research. The only potential risk to patients associated with review
      of the clinical record after the intervention is loss of privacy and
      confidentiality. Appropriate safeguards can be taken to minimize this risk.

PMID- 16908095
TI  - Pregnancy after liver transplantation with tacrolimus.

PMID- 16908097
TI  - The formation of ultra-fine particles during ozone-initiated oxidations with
      terpenes emitted from natural paint.
AB  - The formation of secondary products during the ozone-initiated oxidations with
      biogenic VOCs emitted from natural paint was investigated in this study. Mass
      spectrometry and infrared spectroscopy measurements have shown that the major
      components of gas-phase chemicals emitted from natural paint are monoterpenes
      including alpha- and beta-pinenes, camphene, p-cymene, and limonene. A
      significant formation of gaseous carbonyl products and nano-sized particles (4.4
      168nm) was observed in the presence of ozone. Carboxylic acids were also observed
      to form during the reactions (i.e. formic acid at 0.170ppm and acetic acid at
      0.260ppm). The formation of particles increased as the volume of paint introduced
      into a reaction chamber increased. A secondary increase in the particle number
      concentration was observed after 440min, which suggests further partitioning of
      oxidation products (i.e. carboxylic acids) into the particles previously existing
      in the reaction chamber. The growth of particles increased as the mean particle
      diameter and particle mass concentrations increased during the reaction. The
      experimental results obtained in this study may provide insight into the
      potential exposure of occupants to irritating chemical compounds formed during
      the oxidations of biogenic VOCs emitted from natural paint in indoor
      environments.

PMID- 16908098
TI  - A non-ideal model for predicting the effect of dissolved salt on the flash point
      of solvent mixtures.
AB  - Flash point is one of the major quantities used to characterize the fire and
      explosion hazard of liquids. Herein, a liquid with dissolved salt is presented in
      a salt-distillation process for separating close-boiling or azeotropic systems.
      The addition of salts to a liquid may reduce fire and explosion hazard. In this
      study, we have modified a previously proposed model for predicting the flash
      point of miscible mixtures to extend its application to solvent/salt mixtures.
      This modified model was verified by comparison with the experimental data for
      organic solvent/salt and aqueous-organic solvent/salt mixtures to confirm its
      efficacy in terms of prediction of the flash points of these mixtures. The
      experimental results confirm marked increases in liquid flash point increment
      with addition of inorganic salts relative to supplementation with equivalent
      quantities of water. Based on this evidence, it appears reasonable to suggest
      potential application for the model in assessment of the fire and explosion
      hazard for solvent/salt mixtures and, further, that addition of inorganic salts
      may prove useful for hazard reduction in flammable liquids.

PMID- 16908099
TI  - Biodegradation of meta-fluorophenol by an acclimated activated sludge.
AB  - An acclimated activated sludge was examined for its ability to degrade meta
      fluorophenol as sole carbon source in aerobic batch cultures. The mechanism study
      revealed that the initial step in the aerobic biodegradation of meta-fluorophenol
      was their transformation to fluorocatechol. Following transformation of the
      fluorophenol to fluorocatechol, ring cleavage by catechol 1,2-dioxygenases
      proceeded via an ortho-cleavage pathway, then defluorination occurred.

PMID- 16908100
TI  - Axonal pathways and projection levels of anterior semicircular canal nerve
      activated vestibulospinal neurons in cats.
AB  - Using collision tests of orthodromically and antidromically generated spikes, we
      studied the axonal pathways, axonal projection levels, and soma location of
      anterior semicircular canal (AC) nerve-activated vestibulospinal neurons in
      decerebrate cats. AC nerve-activated vestibulospinal neurons (n=74) were mainly
      located in the ventral portion of the lateral vestibular nuclei and the rostral
      portion of the descending vestibular nucleus, which is consistent with previous
      studies. Of these neurons, 15% projected through the ipsilateral (i-) lateral
      vestibulospinal tract (LVST), 74% projected through the medial vestibulospinal
      tract (MVST), and 11% projected through the contralateral (c-) LVST. The vast
      majority (78%) of AC nerve-activated vestibulospinal neurons were activated
      antidromically only from the cervical segment of the spinal cord; 15% of neurons
      were activated from the T1 segment and only one neuron was activated from the L3
      segment. AC nerve-activated vestibulospinal neurons may primarily target the neck
      muscles and thus contribute to the vestibulocollic reflex. Most of the c-LVST
      neurons were also activated antidromically from the oculomotor nucleus,
      suggesting that they are closely related to the control of combined eye-head
      movements.

PMID- 16908101
TI  - Sample prevalence and molecular characterisation of Cryptosporidium andersoni
      within a dairy herd in the United Kingdom.
AB  - Bovine cryptosporidiosis is usually an acute diarrhoeal disease of young calves
      caused by Cryptosporidium parvum. However, chronic infection with Cryptosporidium
      andersoni has been associated with gastritis, reduced milk yield and poor weight
      gain in adult cattle. Here we describe the first genetic confirmation and
      characterisation of C. andersoni from cattle in the United Kingdom and its sample
      prevalence within a dairy herd. Oocysts measured 7.5+/-0.4 microm x 5.5+/-0.4
      microm (7.0-8.5 microm x 4.5-6.5 microm) with a length-to-width ratio of 1.37
      (1.08-1.60). The within-herd sample prevalence was 16% (95% confidence
      intervals=10.4-21.6%). Nested polymerase chain reaction (PCR)-restriction
      fragment length polymorphism (RFLP) and sequence analysis of the small subunit
      rDNA was used to confirm the species and characterise the isolates. Due to the
      lack of overt, acute, clinical symptoms, the incidence, prevalence and importance
      of this parasite is probably currently underestimated in cattle in the UK. The
      potential for zoonotic transmission is unknown.

PMID- 16908102
TI  - Evaluation of the dietary effects of coenzyme Q in vivo by the oxidative stress
      marker, hydroxyoctadecadienoic acid and its stereoisomer ratio.
AB  - Coenzyme Q (CoQ) is an endogenous enzyme cofactor that may provide protective
      benefits as an antioxidant. In this study, in order to determine whether the
      concentrations of CoQ(9) are associated with the oxidative status in vivo, the
      effects of dietary supplements of CoQ(9) on mice were evaluated by using a new
      biomarker, total hydroxyoctadecadienoic acid (tHODE). Biological samples were
      first reduced and then saponified to convert the various oxidation products of
      linoleates to tHODE. Subsequently, by using GC-MS analyses, we simultaneously
      determined the absolute concentration of tHODE; its stereoisomer ratio, 9- and 13
      (Z,E)-HODE/9- and 13-(E,E)-HODE, which is a measure of the hydrogen donor
      capacity of antioxidants; and the concentration of 8-iso-prostaglandin F(2alpha)
      (8-iso-PGF(2alpha)). Remarkable decreases in tHODE and 8-iso-PGF(2alpha) levels
      were observed in the plasma, erythrocytes, liver, and brain of mice that were
      maintained for 1 month on an alpha-tocopherol (alphaT)-free (E-free) diet
      supplemented with ubiquinone-9 (Q(9); 0.04 wt.%) as compared to those of mice
      that were fed an E-free diet. The (Z,E/E,E) HODE ratio was increased in the
      plasma and erythrocytes of mice that were fed a Q(9)-fortified diet as compared
      to those that were fed an E-free diet. In particular, the (Z,E/E,E) HODE ratios
      in the plasma and brain were significantly correlated with the concentrations of
      ubiquinol-9 (Q(9)H(2)). Further, the liver and brain levels of tHODE and 8-iso
      PGF(2alpha) were significantly correlated with the plasma and erythrocyte levels
      of tHODE and 8-iso-PGF(2alpha), respectively, and in some cases, also exhibited
      significant correlations with antioxidants. These results indicate that the
      plasma and erythrocyte levels of tHODE and its stereoisomeric ratio can be
      prominent biomarkers for the evaluation of the oxidative status and antioxidant
      capacity in vivo, including in the liver and brain, and that CoQ plays a major
      role in the in vivo antioxidant network.

PMID- 16908103
TI  - Contact high-tension electrical burn to the penis: Reconstruction of the defect
      with free radial forearm fasciocutaneous flap and silicon rod, a case report.

PMID- 16908104
TI  - KCNMB1 regulates surface expression of a voltage and Ca2+-activated K+ channel
      via endocytic trafficking signals.
AB  - Voltage-dependent and calcium-activated K(+) (MaxiK, BK) channels are
      ubiquitously expressed and have various physiological roles including regulation
      of neurotransmitter release and smooth muscle tone. Coexpression of the pore
      forming alpha (hSlo) subunit of MaxiK channels with a regulatory beta1 subunit
      (KCNMB1) produces noninactivating currents that are distinguished by high
      voltage/Ca(2+) sensitivities and altered pharmacology [McManus OB, Helms LM,
      Pallanck L, Ganetzky B, Swanson R, Leonard RJ (1995) Functional role of the beta
      subunit of high conductance calcium-activated potassium channels. Neuron 14:645
      650; Wallner M, Meera P, Ottolia M, Kaczorowski G, Latorre R, Garcia ML, Stefani
      E, Toro L (1995) Characterization of and modulation by a beta-subunit of a human
      maxi K(Ca) channel cloned from myometrium. Receptors Channels 3:185-199]. We now
      show that beta1 can regulate hSlo traffic as well, resulting in decreased hSlo
      surface expression. beta1 subunit expressed alone is able to reach the plasma
      membrane; in addition, it exhibits a distinct intracellular punctated pattern
      that colocalizes with an endosomal marker. Coexpressing beta1 subunit with hSlo,
      switches hSlo's rather diffuse intracellular expression to a punctate cytoplasmic
      localization that overlaps beta1 expression. Furthermore, coexpressed beta1
      subunit reduces steady-state hSlo surface expression. Site-directed mutagenesis
      underscores a role of a putative endocytic signal at the beta1 C-terminus in the
      control of hSlo surface expression. We propose that aside from its well
      established role as regulator of hSlo electrical activity, beta1 can regulate
      hSlo expression levels by means of an endocytic mechanism. This highlights a new
      beta1 subunit feature that regulates hSlo channels by a trafficking mechanism.

PMID- 16908105
TI  - Characterization of neogenin-expressing neural progenitor populations and
      migrating neuroblasts in the embryonic mouse forebrain.
AB  - Many studies have demonstrated a role for netrin-1-deleted in colorectal cancer
      (DCC) interactions in both axon guidance and neuronal migration. Neogenin, a
      member of the DCC receptor family, has recently been shown to be a chemorepulsive
      axon guidance receptor for the repulsive guidance molecule (RGM) family of
      guidance cues [Rajagopalan S, Deitinghoff L, Davis D, Conrad S, Skutella T,
      Chedotal A, Mueller B, Strittmatter S (2004) Neogenin mediates the action of
      repulsive guidance molecule. Nat Cell Biol 6:755-762]. Here we show that neogenin
      is present on neural progenitors, including neurogenic radial glia, in the
      embryonic mouse forebrain suggesting that neogenin expression is a hallmark of
      neural progenitor populations. Neogenin-positive progenitors were isolated from
      embryonic day 14.5 forebrain using flow cytometry and cultured as neurospheres.
      Neogenin-positive progenitors gave rise to neurospheres displaying a high
      proliferative and neurogenic potential. In contrast, neogenin-negative forebrain
      cells did not produce long-term neurosphere cultures and did not possess a
      significant neurogenic potential. These observations argue strongly for a role
      for neogenin in neural progenitor biology. In addition, we also observed neogenin
      on parvalbumin- and calbindin-positive interneuron neuroblasts that were
      migrating through the medial and lateral ganglionic eminences, suggesting a role
      for neogenin in tangential migration. Therefore, neogenin may be a multi
      functional receptor regulating both progenitor activity and neuroblast migration
      in the embryonic forebrain.

PMID- 16908106
TI  - Temperament and hypothalamic-pituitary-adrenal axis function in healthy adults.
AB  - BACKGROUND: Traits such as behavioral inhibition and neuroticism have been linked
      to the development of mood and anxiety disorders. Hyperactivity of the
      hypothalamic-pituitary-adrenal (HPA) axis, a manifestation of the stress
      response, is often seen in major depression and has also been demonstrated in
      animals and humans with inhibited temperaments. A recent study found HPA
      hyperactivity in adults with high levels of neuroticism. The present study
      investigated associations of temperament and HPA function in 31 healthy adults.
      METHODS AND MATERIALS: Subjects completed diagnostic interviews, questionnaires,
      and the dexamethasone-/corticotropin-releasing hormone (Dex/CRH) test.
      Temperament was assessed using the Tridimensional Personality Questionnaire
      (TPQ). RESULTS: Novelty Seeking was inversely related to plasma cortisol
      concentrations in the Dex/CRH test. Harm Avoidance and Reward Dependence were not
      significantly associated with cortisol responses in the Dex/CRH test. The results
      were not accounted for by psychiatric symptoms or a history of stress or
      childhood maltreatment. CONCLUSIONS: These findings are consistent with previous
      reports associating temperament factors with HPA axis hyperactivity. Further work
      is needed to replicate these observations and determine whether HPA axis
      dysfunction might account for some of the previously reported association of
      personality factors with mood and anxiety disorders.

PMID- 16908107
TI  - Calculated bioavailable testosterone levels and depression in middle-aged men.
AB  - BACKGROUND: The association between circulating total testosterone (TT) levels
      and depressive symptoms remains unclear. We sought to determine the relationship
      between physiologically active bioavailable testosterone (BT) and depressive
      symptoms in middle-aged men with and without major depressive disorder (MDD).
      METHODS: We assessed and compared calculated BT levels in two groups of middle
      aged men (40-65 years): untreated subjects meeting DSM-IV-TR-defined criteria for
      a major depressive episode as part of major depressive disorder (N=44) and a
      matched non-depressed control group (N=50). RESULTS: Depressed men had lower mean
      BT levels (3.51+/-1.69 vs. 4.69+/-2.04 nmol/L; p=0.008) and TT levels (11.94+/
      4.63 vs. 17.64+/-1.02 nmol/L; p<0.001) when compared to the control group.
      Biochemical hypogonadism (i.e., BT level< or =2.4 nmol/L or TT level< or =12.14
      nmol/L) was also more prevalent in depressed men vs. non-depressed controls (34%
      vs. 6%, p<0.001; 61% vs. 14%, p<0.001, respectively). CONCLUSIONS: Changes in
      physiologically active BT concentration may be a vulnerability factor for
      depressive symptoms in middle-aged depressed men.

PMID- 16908109
TI  - Determination of GHB in urine and serum by LC/MS using a simple one-step
      derivative.
AB  - A sensitive and specific method for the determination of gamma-hydroxybutyric
      acid (GHB) in urine and serum is described. Prior to quantification by LC/MS in a
      Pauli-type ion trap, the molecule is converted by a fast and simple one-step
      procedure into its n-butyl ester derivative. Hexa-deutero GHB has been used as
      internal standard.

PMID- 16908108
TI  - Antinociceptive effect of Hyptis pectinata leaves extracts.
AB  - Oral administration of hexanes, chloroform, and ethyl acetate extracts of the
      leaves of Hyptis pectinata significantly reduced the number of writhing induced
      by acetic acid and increased the response to thermal stimuli in hot-plate test.
      Such effect was completely reversed by the opioid antagonist naloxone.

PMID- 16908110
TI  - It was not me: attribution of blame for criminal acts in psychiatric offenders.
AB  - The current article addresses the psychometric qualities of the German Version of
      Gudjonsson's Blame Attribution Inventory (GBAI), a self-report scale for
      measuring attribution of blame for crime. The GBAI was administered to a criminal
      sample of forensic and criminal inmates (n=107). Findings indicate that the
      German version of the Gudjonsson Blame Attribution Inventory possesses acceptable
      test-retest stability and good internal consistency. Factor analysis reproduced
      the three basic dimensions of the GBAI: external attribution, mental-element
      attribution, and guilt-feeling attribution. Forensic patients had higher mental
      element attribution and guilt-feeling attribution scores than the prison inmates.
      Interestingly, sexual offenders who were prisoners, showed the lowest guilt
      feeling attribution, while sexual offenders who were forensic patients had the
      highest guilt-feeling attribution scores. Since earlier research reported a
      tendency of faking good in sexual offenders, we suggest that the forensic sexual
      offenders may demonstrate a social desirable response tendency in an attempt to
      gain sympathy and/or earlier parole. All in all, our data show that the German
      version of the GBAI is a valuable tool for measuring attributional styles of
      offenders.

PMID- 16908111
TI  - Physiological dysregulation and changes in health in an older population.
AB  - We investigate whether a multi-system measure of physiological dysregulation
      based on 16 biological measures is associated with deterioration in physical and
      mental health over a 3-year period. The data come from a national survey of
      persons 54 and older in Taiwan that collected standard clinical markers related
      to cardiovascular and metabolic function and "non-clinical" measures pertaining
      to the immune, neuroendocrine and sympathetic nervous systems. The dysregulation
      score counts the number of biomarkers for which values are in the lowest or
      highest decile. Statistical models examine whether dysregulation predicts four
      health outcomes (survival, physical functioning, cognitive functioning and
      depressive symptoms), in the presence of extensive controls for baseline health.
      The estimates reveal significant associations between dysregulation and health
      for each outcome, although there is variability across outcomes. The associations
      are often attenuated in the presence of health controls, underscoring the
      importance of longitudinal analysis. This study extends previous research on the
      health consequences of physiological dysregulation by considering a broader range
      of outcomes and biomarkers in a non-Western population-based sample. Our analysis
      suggests that such dysregulation provides early warning signs of a broad range of
      comorbidities.

PMID- 16908112
TI  - Identifying factors that promote functional aging in Caenorhabditis elegans.
AB  - A major feature of aging is a reduction in muscle strength from sarcopenia, the
      loss of muscle mass. Sarcopenia impairs physical ability, reduces quality of life
      and increases the risk of fall and injury. Since aging is a process of stochastic
      decline, there may be many factors that impinge on the progression of sarcopenia.
      Possible factors that may promote muscle decline are contraction-related injury
      and oxidative stress. However, relatively little is understood about the cellular
      pathways affecting muscle aging, in part because lifespan studies are difficult
      to conduct in species with large muscles, such as rodents and primates. For this
      reason, shorter-lived invertebrate models of aging may be more useful for
      unraveling causes of sarcopenia and functional declines during aging. Recent
      studies have examined both physiological and genetic factors that affect aging
      related declines in Caenorhabditis elegans nematodes. In C. elegans, aging leads
      to significant functional declines that correlate with muscle deterioration,
      similar to those documented for longer-lived vertebrates. This article will
      examine the current research into aging-related functional declines in this
      species, focusing on recent studies of locomotory and feeding decline during
      aging in the nematode, C. elegans.

PMID- 16908113
TI  - Phenylobacterium zucineum sp. nov., a facultative intracellular bacterium
      isolated from a human erythroleukemia cell line K562.
AB  - A bacterial strain HLK1(T) was isolated from the human erythroleukemia cell line
      K562. This bacterium is a Gram-negative rod, motile with a polar flagellum. It is
      strictly aerobic, nonfermentative, and oxidase and catalase positive. Its optimal
      growth occurs at 37 degrees C at pH between 6.5 and 7.5. Phylogenetically,
      although it shares 98% similarity with the 16S rRNA of Phenylobacterium
      lituiforme, the DNA-DNA hybridization value between the two species is only 43%.
      HLK1(T) has a DNA G+C content of 71.2+/-0.2 mol%. It is a facultative
      intracellular organism and may have pathogenic relevance with humans and mammals.
      On the basis of the phylogenetic and phenotypic characterization, strain HLK1(T)
      is proposed to be classified in the genus Phenylobacterium, as P. zucineum sp.
      nov. The type strain is HLK1(T) (=CGMCC 1.3786(T), DSM=18354).

PMID- 16908114
TI  - Improved reversed-phase liquid chromatographic method combined with pulsed
      electrochemical detection for the analysis of amikacin.
AB  - A two-step gradient liquid chromatographic method combined with pulsed
      electrochemical detection is described for the determination of amikacin and its
      impurities. The mobile phase is composed of an aqueous solution containing 1.8
      g/l sodium 1-octanesulphonate, 14 ml/l tetrahydrofuran, 50 ml/l of phosphate
      buffer pH 3.0 and sodium sulphate, which was 20 g/l in mobile phase A and 28 g/l
      in mobile phase B. 0.5 M sodium hydroxide was added post-column to enhance the
      detection. An investigation of different reversed-phase columns indicated that
      the Discovery (C18, 5 microm, 250 mm x 4.6 mm i.d.) column was the most suitable.
      Compared to previously published investigations, the proposed method showed
      higher sensitivity and efficiency, allowing the separation of the main component
      amikacin from 16 impurities, 7 of which were of unknown identity. A central
      composite experimental design was used to assess the robustness. The method
      showed good repeatability and linearity in the assay range. The method was
      further applied to analyze some commercial samples.

PMID- 16908115
TI  - The effect of beam size on real-time determination of powder blend homogeneity by
      an online near infrared sensor.
AB  - Online blend uniformity study was conducted with a near infrared (NIR) sensor and
      a simulated formulation consisting of acetaminophen and four excipients.
      Quantitative calibration models were developed and validated for the sensor and
      assay results were obtained in real time for acetaminophen and three excipients.
      Mechanical thief samples were also collected during the study. The samples were
      analyzed offline by a bench-top near infrared spectrometer and used as reference.
      Comparison of the online and offline data shows a significant difference in
      standard deviation for acetaminophen and excipients. R.S.D. data calculated from
      the real-time assay values for acetaminophen was 3.5-13.2-fold lower than those
      from the offline results. The cause for the discrepancy is believed to be the
      large beam size of the online sensor. A simple complete-random-mixture model was
      used to explain the discrepancy. It is concluded that beam size is an important
      factor in quantitative online blending uniformity studies.

PMID- 16908116
TI  - Executive dysfunction and memory in older patients with major and minor
      depression.
AB  - Executive function, known to be impaired during late-life depression, is
      dependent on frontostriatal pathways. Memory is also frequently observed to be
      impaired among late-life depressed patients, so we assessed the possibility that
      executive function mediates the learning and recall deficit as a "downstream"
      effect of the frontostriatal compromise in executive function. A cross-sectional
      sample of minor and major depressed patients (N=95) and nondepressed volunteers
      (N=71), screened for other Axis I disorders, dementia, medical comorbidity, and
      severity of depression, completed a neuropsychological battery that included the
      California Verbal Learning Test and other tests selected for convergent and
      divergent validity testing. Depressed patients differed from controls on learning
      the word list and on verbal and nonverbal executive tasks. Executive function was
      a mediator for depressed patients verbal learning scores (z=-2.67, p=.01). A
      nonverbal executive score also mediated verbal learning (z=-2.18, p=.03)
      indicating convergent validity of executive dysfunction during verbal learning
      exercises. In conclusion, the verbal memory deficits typically attributed to late
      life depression may result from impaired executive functioning during the
      learning phase of the recall task.

PMID- 16908117
TI  - Diversity and evolution of conotoxins based on gene expression profiling of Conus
      litteratus.
AB  - Cone snails are attracting increasing scientific attention due to their
      unprecedented diversity of invaluable channel-targeted peptides. As arguably the
      largest and most successful evolutionary genus of invertebrates, Conus also may
      become the model system to study the evolution of multigene families and
      biodiversity. Here, a set of 897 expressed sequence tags (ESTs) derived from a
      Conus litteratus venom duct was analyzed to illuminate the diversity and
      evolution mechanism of conotoxins. Nearly half of these ESTs represent the coding
      sequences of conotoxins, which were grouped into 42 novel conotoxin cDNA
      sequences (seven superfamilies), with T-superfamily conotoxins being the dominant
      component. The gene expression profile of conotoxin revealed that transcripts are
      expressed with order-of-magnitude differences, sequence divergence within a
      superfamily increases from the N to the C terminus of the open reading frame, and
      even multiple scaffold-different mature peptides exist in a conotoxin gene
      superfamily. Most excitingly, we identified a novel conotoxin superfamily and
      three novel cysteine scaffolds. These results give an initial insight into the C.
      litteratus transcriptome that will contribute to a better understanding of
      conotoxin evolution and the study of the cone snail genome in the near future.

PMID- 16908118
TI  - Individual trajectories in stress covary with immunity during recovery from
      cancer diagnosis and treatments.
AB  - Research connects stressful events with altered immune regulation, but the role
      of subjective stress is uncertain. Using a longitudinal design, we provide a
      statistically powerful test of the relationship between subjective stress
      (perceived stress, emotional distress) and immunity (T cell blastogenesis,
      natural killer cell cytotoxicity, [NKCC]) as individuals adjust to a severe
      stressor, a cancer diagnosis and its treatments. Women with regional breast
      cancer (N=113) were assessed at diagnosis/surgery and reassessed 4, 8, 12, and 18
      months later. Latent growth curve analysis tested two hypotheses: (1) initial
      levels of subjective stress will correlate inversely with initial levels of
      immunity, and (2) rate of change in subjective stress will correlate inversely
      with rate of change in immunity. As predicted by Hypothesis 1, participants with
      high initial subjective stress showed poor initial blastogenesis. As predicted by
      Hypothesis 2, participants exhibiting an early, rapid decline in subjective
      stress also showed rapid improvement in NKCC. Follow-up analyses revealed
      perceived stress to be strongly related to immune function, while emotional
      distress was not. This is the first study to investigate trajectories in stress
      and immunity during recovery from a major stressor. Results imply that NK and T
      cells are sensitive to different aspects of the stress response. While T cell
      blastogenesis correlated with initial (peak) subjective stress, NKCC correlated
      with change (improvement) in subjective stress. These data highlight the
      importance of subjective stress, particularly stress appraisals, in the immune
      response to a major stressor.

PMID- 16908119
TI  - Risk factors for Clostridium difficile toxin-positive nosocomial diarrhoea.
AB  - Data were retrieved from the records of all patients from whom stool was sent for
      Clostridium difficile toxin testing during the year 2001. Toxin-positive and 
      negative patients were compared by bivariate analysis and regression models.
      Eight hundred samples from 610 patients were sent for C. difficile toxin testing.
      Charts of 535 patients (88%) were available for analysis. Of those, 17% had a
      positive toxin test whilst 83% had a negative toxin test. There was no difference
      in the number of daily bowel movements between the two groups. Toxin-positive
      patients were older (P<0.0001), more often came from nursing homes (P<0.05), had
      higher leukocyte counts (P<0.001), higher blood urea nitrogen (P<0.01), lower
      serum albumin (P<0.01) and more often received diuretics (P<0.01) and clindamycin
      (P<0.05). Logistic regression analysis showed that previous antibiotic-associated
      diarrhoea was the most significant risk factor for toxin-positive diarrhoea
      (P<0.001), followed by clindamycin treatment (P<0.005), diuretics (P<0.005) and
      older age (P<0.05). Another logistic model showed the contribution of macrolides
      (P<0.05) to the development of hospital-acquired diarrhoea.

PMID- 16908120
TI  - Voriconazole brain tissue levels in rhinocerebral aspergillosis in a successfully
      treated young woman.
AB  - Invasive aspergillosis of the central nervous system has a mortality rate
      exceeding 90%. We describe a 29-year-old woman with a medical history of chronic
      polyarthritis who developed a proven rhinocerebral Aspergillus fumigatus
      infection refractory to first-line treatment with liposomal amphotericin B. The
      patient responded successfully to salvage combination treatment with voriconazole
      and caspofungin. Furthermore, for the first time, voriconazole levels in an
      intracerebral abscess were measured in this patient undergoing voriconazole oral
      therapy.

PMID- 16908121
TI  - Increased amikacin dosage requirements in burn patients receiving a once-daily
      regimen.
AB  - Altered pharmacokinetics in burn patients may affect antibiotic plasma
      concentrations. Typical once-daily dosing (ODD) of 15 mg/kg amikacin (AMK) in
      burn patients does not always produce peak concentrations (C(max)) reaching the
      therapeutic objective of six to eight times the minimal inhibitory concentration
      (MIC). We recorded plasma concentrations following administration of 20 mg/kg AMK
      in burn patients and studied factors affecting pharmacokinetics. Mean C(max) was
      48.3+/-10.8 mg/L and the C(max)/MIC ratio was 6+/-1.35. Statistical analysis
      demonstrated a relationship between C(max) and the area of the burn and Unit Burn
      Standard, and between AMK clearance and creatinine clearance (Cl(CR)). We
      conclude that ODD regimens of AMK in patients with burns >15% body surface area
      and/or with Cl(CR) >120 mL/min could require doses >20 mg/kg to reach adequate
      C(max). In all cases, patient therapeutic drug monitoring is essential to ensure
      the safe usage of these dosing recommendations.

PMID- 16908122
TI  - The neuronal ceroid-lipofuscinoses: from past to present.
AB  - The neuronal ceroid-lipofuscinoses (NCLs) are inherited lysosomal storage
      diseases and constitute the most common group of children's progressive
      encephalopathies. Most childhood forms of NCL are clinically characterized by
      progressive loss of vision as well as mental and motor deterioration, epileptic
      seizures, and premature death, while the rare adult forms are dominated by
      dementia. All forms of NCL share common pathomorphological features.
      Autofluorescent, periodic acid-Schiff- and Sudan black B-positive granules,
      resistant to lipid solvents, accumulate in the cytoplasm of most nerve cells, and
      there is progressive and remarkably selective neuronal degeneration and loss. For
      a long time, the NCLs were grouped under the heading of the "amaurotic family
      idiocies" and conceived as lipidoses. However, in the late 1980s and 1990s the
      NCL storage cytosomes were shown to consist largely of two hydrophobic proteins:
      either subunit c of mitochondrial ATP synthase or sphingolipid activator proteins
      A and D. Since 1995 numerous mutations in at least seven different genes have
      been shown to underlie the multiple human and animal forms of NCL. This review
      discusses the historical evolution of the NCL concept and the impact of the
      recent biochemical and molecular genetic findings on our views on the
      classification and pathogenesis of these devastating brain disorders.

PMID- 16908123
TI  - Fungi and fungal toxins as weapons.
AB  - Recent aggressive attacks on innocent citizens have resulted in governments
      increasing security. However, there is a good case for prevention rather than
      reaction. Bioweapons, mycotoxins, fungal biocontrol agents (FBCA), and even
      pharmaceuticals contain, or are, toxins and need to be considered in the context
      of the new paradigm. Is it desirable to discuss such issues? None of the fungi
      are (a) as toxic as botulinum toxin from Clostridium botulinum, and (b) as
      dangerous as nuclear weapons. One toxin may be defined as a pharmaceutical and
      vice versa simply by a small change in concentration or a moiety. Mycotoxins are
      defined as naturally occurring toxic compounds obtained from fungi. They are the
      biggest chronic health risk when incorporated into the diet. The current list of
      fungal toxins as biochemical weapons is small, although awareness is growing of
      the threats they may pose. T-2 toxin is perhaps the biggest concern. A clear
      distinction is required between the biological (fungus) and chemical (toxin)
      aspects of the issue. There is an obvious requirement to be able to trace these
      fungi and compounds in the environment and to know when concentrations are
      abnormal. Many FBCA, produce toxins. This paper indicates how to treat
      mycotoxicosis and decontaminate mycotoxins. There is considerable confusion and
      inconsistency surrounding this topic which requires assessment in an impartial
      and scientific manner.

PMID- 16908124
TI  - Seven new calochroid and fulvoid species of Cortinarius.
AB  - We describe seven new European species of Cortinarius. All species are based on
      analyses of morphological and DNA sequence data. They all belong to a well
      supported clade comprising most species traditionally treated in Cortinarius
      subgenus Phlegmacium sections Fulvi and Calochroi (i.e. the/Calochroi clade). All
      taxa are either fulvoid (containing anthraquinoid pigments) or calochroid
      (without these pigments). Morphological and ecological data are presented for all
      species and compared with similar species. A dichotomous key is presented for C.
      calochrous and similar species, including all six newly described calochroid
      species. The calochroid species C. albertii, C. chailluzii, C. cisticola, C.
      sancti-felicis, C. selandicus and C. vesterholtii spp. nov., and the fulvoid
      species C. langeorum sp. nov. are described.

PMID- 16908125
TI  - Ribosomal and RPB2 DNA sequence analyses suggest that Sporidesmium and
      morphologically similar genera are polyphyletic.
AB  - Sporidesmium and morphologically similar dematiaceous, hyphomycetous genera are
      characterised by holoblastic phragmoconidia produced on proliferating or non
      proliferating conidiophores. They include a number of asexual (anamorphic) genera
      taxonomically segregated from Sporidesmium sensu lato and are similar in having
      schizolytic conidial secession. The taxonomy of these ubiquitous asexual fungi
      and their affinities with known Ascomycetes are, however, still obscure. This
      study incorporates a phylogenetic investigation, based on the LSU nu-rDNA and RNA
      polymerase II second largest subunit (RPB2) gene sequence, to assess the possible
      familial placement of Ellisembia, Linkosia, Repetophragma, Sporidesmiella,
      Sporidesmium and Stanjehughesia, and justify whether anamorphic characters are
      proper phylogenetic indicators. Phylogenies provide conclusive evidence to
      suggest that Sporidesmium is not monophyletic and species are phylogenetically
      distributed in two major ascomycete classes, Dothideomycetes and Sordariomycetes.
      Morphologies currently used in their classification have undergone convergent
      evolution and are not phylogenetically reliable. The possible teleomorphic
      affinities of these anamorphic genera are discussed in light of morphology and
      molecular data. As these anamorphs, in most cases, are the sole known morph of
      the holomorph, it is proposed that in the absence of or failure to detect their
      teleomorphic phase, the anamorph names should be used for the holomorph.

PMID- 16908126
TI  - Adjunct armodafinil improves wakefulness and memory in obstructive sleep
      apnea/hypopnea syndrome.
AB  - OBJECTIVE: Armodafinil is the R-enantiomer of racemic modafinil and has a
      significantly longer half-life than the S-enantiomer. This study evaluated
      armodafinil 150 mg/day as an adjunct treatment for residual excessive sleepiness
      in patients with obstructive sleep apnea/hypopnea syndrome (OSA/HS) who were
      otherwise well controlled with nasal continuous positive airway pressure (nCPAP).
      We assessed the ability of armodafinil to improve wakefulness and cognition and
      reduce fatigue in this population. METHODS: In this 12-week, randomized, double
      blind study, patients (n=259) received armodafinil (150 mg) or placebo once
      daily. Efficacy assessments at baseline and weeks 4, 8, and 12 included the
      Maintenance of Wakefulness Test (MWT), Clinical Global Impression of Change (CGI
      C), Cognitive Drug Research battery, Epworth Sleepiness Scale, and Brief Fatigue
      Inventory. RESULTS: At final visit, mean (SD) MWT sleep latency increased from
      baseline by 2.3 (7.8) min with armodafinil and decreased by 1.3 (7.1) min in the
      placebo group (P=0.0003). Armodafinil improved clinical condition (CGI-C, 71% vs.
      53% for armodafinil and placebo, respectively; P=0.0069). Armodafinil
      significantly improved episodic secondary memory (P=0.0102) and patient-estimated
      wakefulness (P<0.01) and reduced fatigue (P<0.05) compared with placebo.
      Armodafinil did not adversely affect nCPAP use. The most common adverse event
      associated with armodafinil was headache. Sleep macroarchitecture was not altered
      by armodafinil. CONCLUSION: Adjunct treatment with armodafinil significantly
      improved alertness, overall clinical condition, and long-term memory. Armodafinil
      also reduced fatigue and the impact of sleepiness on daily activities in patients
      with OSA/HS who have residual excessive sleepiness notwithstanding regular use of
      nCPAP. Armodafinil was well tolerated.

PMID- 16908127
TI  - Early detection of COPD: a case finding study in general practice.
AB  - OBJECTIVES: To estimate the prevalence of undiagnosed chronic obstructive
      pulmonary disease (COPD) in a population of general practice patients at risk for
      developing COPD. A further aim was to evaluate the presence of respiratory
      symptoms as a predictor for the diagnosis of COPD. METHODS: This study was
      conducted by eight general practitioners (GP) in six semi-rural general
      practices. During two consecutive months all patients attending their GP were
      included if they met the following criteria: current smokers between 40 and 70 yr
      of age, and a smoking history of at least 15 pack-years. A questionnaire
      regarding smoking history, respiratory symptoms, exposure to dust or chemical
      fumes, and history of respiratory diseases was completed for all patients.
      Subjects without known COPD were invited for spirometric testing. RESULTS: Off
      the 146 general practice patients included, 17.1% already had an established COPD
      diagnosis. Screening by spirometry revealed a 46.6% prevalence of COPD.
      Underdiagnosis of COPD was more frequent in the younger age categories (40-49 Yr;
      50-59 Yr). Objective wheezing was the only sign that was significantly more
      frequent in COPD patients than in non-COPD patients (P<0.001). Patients with
      previously known COPD were significantly older, and complained more of chronic
      cough and fatigue than newly detected patients. CONCLUSION: Almost half of a
      general practice population of current smokers between 40 and 70 years of age,
      with a smoking history of at least 15 pack-years, was diagnosed with COPD, and
      roughly two thirds of these were newly detected as a result of the case finding
      programme.

PMID- 16908128
TI  - From the membrane to the nucleus and back again: bifunctional focal adhesion
      proteins.
AB  - Cell substratum adhesion influences a variety of processes including motility,
      proliferation and survival. In recent years, it has become clear that there are
      proteins that are capable of shuttling between cell adhesion zones and the
      nucleus, providing a mechanism for transcellular coordination and communication.
      Recent findings have given insight into the physiological signals that trigger
      trafficking of focal adhesion constituents to the nucleus, where they make
      diverse contributions to the control of gene expression.

PMID- 16908129
TI  - Microbiological assessments of compost toilets: in situ measurements and
      laboratory studies on the survival of fecal microbial indicators using sentinel
      chambers.
AB  - Compost toilet systems were assessed for their ability to reduce microbial
      indicators and pathogens. Bacterial pathogens were not detected in any samples
      indicating a low survival rate in composting feces and/or an initial low
      occurrence. Indicator bacteria showed large variations with no clear trend of
      lower bacterial numbers after longer storage. In controlled composting
      experiments, thermophilic conditions were only reached when amendments were made
      (grass and a sugar solution). Even then it was impossible to ensure a homogenous
      temperature in the composting fecal material and therefore difficult to achieve a
      uniform reduction and killing of indicator organisms. Presumptive thermotolerant
      coliforms, Salmonella typhimurium Phage 28 B and eggs of Ascaridia galli, proved
      useful as indicators. However, regrowth was detected for enterococci and total
      numbers of bacteria grown at 36 degrees C. These indicator parameters may
      therefore overestimate the level of other (pathogenic) bacteria present in the
      material and can not be recommended for use as reliable indicator organisms in
      composting toilet systems. The addition of indicator bacteria to fecal material
      contained in semi-permeable capsules proved to be a useful technique to ensure
      that microorganisms were contained in a small test volume.

PMID- 16908130
TI  - An amperometric uric acid biosensor based on modified Ir-C electrode.
AB  - The level of uric acid (UA) has a high relationship with gout, hyperuricemia and
      Lesch-Nyan syndrome. The determination of UA is an important indicator for
      clinics and diagnoses of kidney failure. An amperometric UA biosensor based on an
      Ir-modified carbon (Ir-C) working electrode with immobilizing uricase (EC
      1.7.3.3) was developed by thick film screen printing technique. This is the first
      time to report the utilization of an uricase/Ir-C electrode for the determination
      of UA by using chronoamperometric (CA) method. The high selectivity of UA
      biosensor was achieved due to the reduction of H(2)O(2) oxidation potential based
      on Ir-C electrode. Using uricase/Ir-C as the sensing electrode, the interference
      from the electroactive biological species, such as ascorbic acid (AA) and UA
      (might be directly oxidized on the sensing electrode) was slight at the sensing
      potential of 0.25 V (versus Ag/AgCl). UA was detected amperometrically based on
      uricase/Ir-C electrode with a sensitivity of 16.60 microAmM(-1) over the
      concentration range of 0.1-0.8 mMUA, which was within the normal range in blood.
      The detection limit of UA biosensor was 0.01 mM (S/N=6.18) in pH 7 phosphate
      buffer solution (PBS) at 37 degrees C. The effects of pH, temperature, and
      enzymatic loading on the sensing characteristics of the UA biosensor were also
      investigated in this study.

PMID- 16908131
TI  - The tumour suppressor hSNF5/INI1 controls the differentiation potential of
      malignant rhabdoid cells.
AB  - Malignant rhabdoid tumours (MRT) are highly aggressive cancers of early childhood
      that arise in different organs or tissues. The unifying criterion for these
      tumours is the presence of inactivating mutations of the hSNF5/INI1 tumour
      suppressor gene which encodes a core subunit of the chromatin remodelling SWI/SNF
      complex. Using a variety of markers we analysed the phenotypic traits of MON and
      DEV cell lines derived respectively from an undifferentiated abdominal MRT and
      from a brain MRT. DEV cells express spontaneously a wide range of neural and
      glial markers. It can be induced to differentiate into the neural lineage
      following hSNF5/INI1 expression with appearance of neurite processes, strong
      increase of neural markers and decrease of glial markers. A less pronounced
      neural differentiation is also observed with MON cells, which possess more
      primitive polyphenotypic features with positivity for markers from the three
      embryonic layers. Finally, we show that the neural differentiation of rat PC12
      cells in the presence of nerve growth factor (NGF) is strongly impaired when
      hSNF5/INI1 expression is inhibited by RNA interference. Altogether these results
      indicate that hSNF5/INI1 is an essential subunit for SWI/SNF-dependant induction
      of neural differentiation programs. Further experiments should enable
      documentation of whether it provides instructive or permissive signals for
      differentiation.

PMID- 16908132
TI  - Numerous high-risk epithelial lesions in familial breast cancer.
AB  - PURPOSE: To assess the occurrence of high-risk epithelial lesions in women of
      breast cancer families with and without a BRCA mutation. PATIENTS AND METHODS:
      Prospective study of women at very high risk of breast cancer undergoing
      prophylactic mastectomy (68 BRCA1 mutation carriers, 14 BRCA2 mutation carriers
      and 24 non-BRCA mutation carriers). RESULTS: The prevalence of high-risk lesions
      is equal in women with a BRCA1 or a BRCA2 mutation, but is higher in non-BRCA
      mutation carriers: all lesions 43% versus 71% (p=0.02), atypical lobular
      hyperplasia 26% versus 67% (p=0.001), atypical ductal hyperplasia 17% versus 42%
      (p=0.01), lobular carcinoma-in situ 15% versus 29% (p=0.10) and ductal carcinoma
      in situ 9% versus 17% (p=0.25). The presence of high-risk lesions is related to
      absence of a BRCA mutation and to age over 40 years. CONCLUSION: Women with an
      autosomal dominant family history for breast cancer, with and without a BRCA
      mutation are prone to develop high-risk epithelial lesions, especially over 40
      years.

PMID- 16908133
TI  - Feasibility study of a pilot-scale sewage treatment system combining an up-flow
      anaerobic sludge blanket (UASB) and an aerated fixed bed (AFB) reactor at ambient
      temperature.
AB  - A feasibility test of a 17 m3-pilot-scale sewage treatment system was carried out
      by continuous feeding of raw municipal sewage under ambient temperature
      conditions. The system consisted of a UASB and an aerated fixed bed reactor. Some
      of the effluent from the fixed bed reactor was returned to the UASB influent in
      order to provide a sulfate source. The total BOD of 148-162 mg l(-1) in the
      influent was reduced to a more desirable 11-25 mg l(-1) in the final effluent.
      The levels of methane-producing activity from acetate and H2/CO2 gas at 10
      degrees C were only 2% and 0% of those at 35 degrees C, respectively. On the
      other hand, the sulfate-reducing activity levels of the UASB sludge were
      relatively high at 10 degrees C, for example, 18% for acetate and 9% for H2/CO2
      gas, compared to the activity levels at 35 degrees C. Therefore, BOD oxidization
      by sulfate reduction in the UASB was greater than that by methane production
      under low temperature conditions. This sulfate-reducing activity tended to be
      proportional to the copy number of adenosine-5'-phosphosulfate (APS) reductase
      genes in DNA extracted from the sludge.

PMID- 16908135
TI  - Antitumour properties of fluorinated benzothiazole-substituted hydroxycyclohexa
      2,5-dienones ('quinols').
AB  - The synthesis and in vitro antitumour evaluation of a new series of fluorinated
      benzothiazole-substituted 4-hydroxycyclohexa-2,5-dienones ('quinols') is
      described. The new compounds were found to be of comparable activity compared to
      the non-fluorinated precursor PMX 464, in terms of antiproliferative activity in
      sensitive human cancer cell lines (nanomolar GI(50) values) and inhibitory
      activity against the thioredoxin signalling system.

PMID- 16908134
TI  - Peptidyl-urea based inhibitors of soluble epoxide hydrolases.
AB  - We prepared a series of amino acid derived cyclohexyl and adamantyl ureas and
      tested them as inhibitors of the human soluble epoxide hydrolase, and obtained
      very potent compounds (K(I)=15nM) that are >10-fold more soluble than previously
      described sEH inhibitors. While our lead compound 2 showed low apparent
      bioavailability in dogs and rats, this series of compounds revealed that sEH
      inhibitor structures could accept large groups that could lead to better orally
      available drugs.

PMID- 16908136
TI  - In vitro and in vivo efficacy and in vitro metabolism of 1-phenyl-3-aryl-2-propen
      1-ones against Plasmodium falciparum.
AB  - Investigation of a series of 1-phenyl-3-aryl-2-propen-1-ones resulted in the
      identification of nine inhibitors with submicromolar efficacy against at least
      one Plasmodium falciparum strain in vitro. These inhibitors were inactive when
      given orally in a Plasmodium berghei infected mouse model. Significant compound
      degradation occurred upon their exposure to a liver microsome preparation,
      suggesting metabolic instability may be responsible for the lack of activity in
      vivo.

PMID- 16908137
TI  - Electrochemiluminescence determination of pipemidic acid using sulfite as energy
      transfer mediator.
AB  - An electrochemiluminescence (ECL) based on energy transfer from electro-generated
      triplet sulfur dioxide to pipemidic acid (PPA) was studied. A weak ECL from
      triplet sulfur dioxide (3)SO2 * was observed when sulfite was electrochemically
      oxidized in sulfuric acid solution on a Pt electrode. When PPA was present, the
      weak ECL was enhanced. The enhanced ECL was attributed to energy transfer from
      (3)SO2 * to PPA. Based on the enhanced ECL, a flow-injection (FIA) ECL method for
      the determination of PPA was proposed. The proposed method allowed the
      measurement of PPA over the range of 1.0x10(-7) to 2.0x10(-5)moll(-1). The
      detection limit was 3.9x10(-8)moll(-1), and the relative standard deviation for
      1.0x10(-6)moll(-1) PPA (n=9) was 1.3%. This method was evaluated by the analysis
      of PPA in pharmaceutical preparations and urine samples.

PMID- 16908138
TI  - Improved replicon cellular activity of non-nucleoside allosteric inhibitors of
      HCV NS5B polymerase: from benzimidazole to indole scaffolds.
AB  - Benzimidazole-based allosteric inhibitors of the hepatitis C virus (HCV) NS5B
      polymerase were diversified to a variety of topologically related scaffolds.
      Replacement of the polar benzimidazole core by lipophilic indoles led to
      inhibitors with improved potency in the cell-based subgenomic HCV replicon
      system. Transposing the indole scaffold into a previously described series of
      benzimidazole-tryptophan amides generated the most potent inhibitors of HCV RNA
      replication in cell culture reported to date in this series (EC(50) approximately
      50 nM).

PMID- 16908139
TI  - Synthesis and HIV-integrase strand transfer inhibition activity of 7
      hydroxy[1,3]thiazolo[5,4-b]pyridin-5(4H)-ones.
AB  - An efficient synthesis of methyl 7-hydroxy[1,3]thiazolo[5,4-b]pyridin-5(4H)-one-6
      carboxylates (8-10 and 16) and 6-carboxamides (17-20) is described. Sub
      micromolar enzyme inhibition of HIV integrase was achieved with several
      carboxamide analogs which were superior to their carboxylic ester congeners.

PMID- 16908141
TI  - Free radical scavengers from the medicinal mushroom Inonotus xeranticus and their
      proposed biogenesis.
AB  - New free radical scavengers, inoscavin D (1) and methylinoscavin D (2), were
      isolated from the methanolic extract of the fruiting bodies of Inonotus
      xeranticus (Hymenochaetaceae), along with the known compounds phelligridin D (3),
      3,4-dihydroxybenzaldehyde (4), and 3,4-dihydroxybenzoic acid (5). Their
      structures were established by various spectroscopic analyses. Compounds 1 and 3
      were proposed to be biosynthesized from the oxidative coupling of the precursor
      hispidin with 3,4-dihydroxybenzaldehyde and 3,4-dihydroxybenzoic acid,
      respectively. These compounds exhibited significant scavenging activity against
      the ABTS radical cation, and compounds 2 and 4 displayed moderate superoxide
      radical scavenging activity.

PMID- 16908140
TI  - Inhibitory mode of 2-acetoxyphenyl alkyl sulfides against COX-1 and COX-2: QSAR
      analyses.
AB  - Selective inhibition of cyclooxygenase-2 (COX-2) inhibitors is an important
      strategy in design of potent anti-inflammatory compounds with significantly
      reduced side effects. Therefore, QSAR studies of 2-acetoxyphenyl alkyl sulfides
      were performed using Bioloom, CAChe 6.1, and Dragon 3.0 for the COX-2 and COX-1
      inhibition. The analyses have produced good predictive and statistically
      significant QSAR models. These studies suggest that lipophilicity affects both
      COX-1 and COX-2 inhibition in different manner and indicator variables like
      presence of aromatic ring and triple bond play an important role in COX-2
      selectivity. Branching in the molecule, higher path length 6 rich in
      polarizability, and lesser number of carbonyl groups would be favorable for COX-2
      inhibition. Fourth highest eigenvalue of burden matrix corresponding to atomic
      mass would be favorable for COX-2 inhibition and sixth lowest eigenvalue of
      burden matrix corresponding to Sanderson electronegativities is conducive for COX
      1 inhibition. Lower path length 3 rich in atomic mass and lesser degree of
      unsaturation in the molecule would be favorable for COX-1 inhibition.

PMID- 16908142
TI  - Novel 6-O-acylated vitamin C derivatives as hyaluronidase inhibitors with
      selectivity for bacterial lyases.
AB  - Previously, we identified ascorbic acid 6-O-hexadecanoate as an up to 1500 times
      more potent inhibitor of bacterial and bovine hyaluronidases than the parent
      compound, vitamin C, and determined a crystal structure of hyaluronidase from
      Streptococcus pneumoniae in complex with the inhibitor. As the alkanoyl chain
      interacts with a hydrophobic patch of the enzyme we synthesized other 6-O
      acylated vitamin C derivatives bearing various lipophilic residues and
      investigated the inhibition of Streptococcus agalactiae strain 4755 hyaluronidase
      (SagHyal(4755)) and of bovine testicular hyaluronidases (BTH) in a turbidimetric
      assay. All compounds showed selectivity for the bacterial enzyme. Whereas vitamin
      C 6-O-hexanoate only weakly inhibited SagHyal(4755), the inhibition of both
      enzymes increased with the length of the aliphatic chain. In the case of the 6-O
      octadecanoate, IC(50) values of 0.9 and 39microM for SagHyal(4755) and BTH,
      respectively, were determined. Partial replacement of the aliphatic chain with a
      phenyl, p-phenylene or p-biphenylyl group resulted in inhibitors with activity in
      the lower micromolar range, too. The title compounds are among the most potent
      inhibitors of both enzymes known to date.

PMID- 16908143
TI  - Synthesis and anti-HIV-1 activity of a novel series of 1,4,2-benzodithiazine
      dioxides.
AB  - Previously, we discovered a series of novel benzodithiazines-dioxides with both
      antiviral and anticancer activities. In order to design compounds with distinct
      antiviral properties, we prepared new compounds with modifications on the
      imidazole and pyrimidine rings. Herein, we present the synthesis and antiviral
      activity of 8-chloro-2,3-dihydroimidazo[1,2-b][1,4,2]benzodithiazine 5,5-dioxides
      (22, 23, 30, and 31) and 9-chloro-2,3,4-trihydropyrimido[1,2
      b][1,4,2]benzodithiazine 6,6-dioxides (14, 24, 25, and 27). We successfully
      identified a lead compound with remarkable anti-HIV-1 activity
      (EC(50)=0.09microM). These compounds showed minimal cytotoxicity and are
      therefore suitable for antiviral development.

PMID- 16908144
TI  - A novel antiproliferative agent, phenylpyridineylbutenol, isolated from
      Streptomyces sp.
AB  - A novel compound showing antiproliferative effect was isolated from Streptomyces
      sp. Its structure was determined based on the interpretation of the NMR spectra,
      and its conformation was elucidated using molecular modeling and 2D NOESY. It was
      determined to be (E)-4-phenyl-3-(pyridine-2-yl)but-2-en-1-ol.

PMID- 16908145
TI  - Design and synthesis of a series of novel pyrazolopyridines as HIF-1alpha prolyl
      hydroxylase inhibitors.
AB  - Recently resolved X-ray crystal structure of HIF-1alpha prolyl hydroxylase was
      used to design and develop a novel series of pyrazolopyridines as potent HIF
      1alpha prolyl hydroxylase inhibitors. The activity of these compounds was
      determined in a human EGLN-1 assay. Structure-based design aided in optimizing
      the potency of the initial lead (2, IC(50) of 11 microM) to a potent (11l, 190
      nM) EGLN-1 inhibitor. Several of these analogs were potent VEGF inducers in a
      cell-based assay. These pyrazolopyridines were also effective in stabilizing HIF
      1alpha.

PMID- 16908146
TI  - 2-(3-Amino-3-deoxy-beta-D-xylofuranosyl)thiazole-4-carboxamide: a new tiazofurin
      analogue with potent antitumour activity.
AB  - A new tiazofurin analogue, 2-(3-amino-3-deoxy-beta-d-xylofuranosyl)thiazole-4
      carboxamide (3), was synthesized starting from d-glucose and evaluated for its in
      vitro antiproliferative activity against a panel of human tumour cell lines.
      Compound 3 exhibited the most powerful cytotoxicity against K562 cells, being
      approximately 100-fold more potent than tiazofurin. This analogue was also active
      against Jurkat, HT-29 and HeLa malignant cells, with respective IC(50) values
      being ca. 2-, 27- and 17-fold lower than those observed for tiazofurin.
      Remarkably, compound 3 did not exhibit any significant cytotoxicity towards
      normal foetal lung MRC-5 cell line.

PMID- 16908147
TI  - Phosphodiester modification by zinc metalated adenine polymer with carboxyl
      pendants.
AB  - This report describes a novel carboxyl pendant containing adenylated polymeric
      template, its metalation with Zn (II), and manifestation of catalytic activity
      for the hydrolysis of model phosphodiester, bis(p-nitrophenyl) phosphate (bNPP),
      and plasmid cleavage. Observation of a bell-shaped pH-K(obs) profile suggested
      influence of pH variation over hydrolysis rate. This metalated polymer also
      afforded facile relaxation of pBR322 supercoiled DNA, with an interesting
      reusability feature intricately associated with heterogeneous catalysis.

PMID- 16908149
TI  - Design and synthesis of substituted pyridine derivatives as HIF-1alpha prolyl
      hydroxylase inhibitors.
AB  - Structure-guided de novo drug design led to the identification of a novel series
      of substituted pyridine derivatives as HIF-1alpha prolyl hydroxylase inhibitors.
      Pyridine carboxyamide derivatives bearing a substituted aryl group at the 5
      position of the pyridine ring show appreciable activity, while constraining the
      side chain by placing a pyrazole carboxylic acid generated a potent lead series
      with consistent activity against EGLN-1.

PMID- 16908150
TI  - Ureas with histamine H3-antagonist receptor activity--a new scaffold discovered
      by lead-hopping from cinnamic acid amides.
AB  - A group of tri and tetrasubstituted urea derivatives have been found to be hH(3)
      antagonists. The most potent compounds were found in the class of (piperazine-1
      yl)-(piperidine-1-yl)-methanones which in addition showed negligible hERG
      inhibition.

PMID- 16908148
TI  - Application of azide-alkyne cycloaddition 'click chemistry' for the synthesis of
      Grb2 SH2 domain-binding macrocycles.
AB  - Copper (I) promoted [3+2] Huisgen cycloaddition of azides with terminal alkynes
      was used to prepare triazole-containing macrocycles based on the Grb2 SH2 domain
      binding motif, 'Pmp-Ac(6)c-Asn', where Pmp and Ac(6)c stand for 4
      phosphonomethylphenylalanine and 1-aminocyclohexanecarboxylic acid, respectively.
      When cycloaddition reactions were conducted at 1mM substrate concentrations,
      cyclization of monomeric units occurred. At 2mM substrate concentrations the
      predominant products were macrocyclic dimers. In Grb2 SH2 domain-binding assays
      the monomeric (S)-Pmp-containing macrocycle exhibited a K(d) value of 0.23microM,
      while the corresponding dimeric macrocycle was found to have greater than 50-fold
      higher affinity. The open-chain dimer was also found to have affinity equal to
      the dimeric macrocycle. This work represents the first application of 'click
      chemistry' to the synthesis of SH2 domain-binding inhibitors and indicates its
      potential utility.

PMID- 16908151
TI  - Synthesis and monoamine transporter affinity of 2beta-carbomethoxy-3beta-(4'-p
      substituted phenyl)-piperidine analogs of cocaine.
AB  - A series of novel piperidine based analogs of cocaine was synthesized and
      evaluated in vitro against the three monoamine transporters to develop new
      potential selective SERT radiotracers. Modification of the phenyl substitution
      with five-membered heterocyclic groups resulted in a wide affinity and
      selectivity scale. Radiolabeling and mouse in vivo study was performed on the
      piperidine analog of ZIENT, which crossed the blood-brain barrier but failed to
      selectively accumulate in the regions of the brain rich in SERT.

PMID- 16908152
TI  - Primary therapy with ECF in combination with a GnRH analog in premenopausal women
      with hormone receptor-positive T2-T4 breast cancer.
AB  - Patients with hormone receptor-positive tumors less often show a pathological
      complete response (pCR) than do those with hormone receptor-negative tumors. The
      addition of endocrine therapies may improve the clinical benefits of primary
      therapies in these patients. We investigated the efficacy of the
      epirubicin+cisplatin+fluorouracil (ECF) as continuous infusion) regimen in
      association with a gonadotropin-releasing hormone (GnRH) analog in 36
      premenopausal women with T2-T4a-d N0-2 M0 ER and/or PgR-positive breast cancer.
      Median age was 39.5 years (range 26-53). Clinical response (complete or partial)
      was observed in 27 out of 36 patients (75% 95% CI 57.8-87.9%) and a pCR was
      observed in four patients (11%). Nine (25%) patients had stable disease and no
      progression was observed. Twenty-one patients (58%) were submitted for breast
      conserving surgery and 15 had a radical mastectomy. No baseline clinical and
      biological characteristics significantly correlated with response. Thirty out of
      31 patients evaluable for endocrine assessment had documented ovarian
      suppression, which occurred after a median of 28 days (range 20-43). We conclude
      that the combination of ECF and a GnRH analog is associated with a high response
      rate in the primary treatment of breast cancer. Further studies combining
      chemotherapy and endocrine agents are warranted in patients with hormone receptor
      positive tumors.

PMID- 16908153
TI  - Timing phases of the sit-to-walk movement: validity of a clinical test.
AB  - The sit-to-walk (STW) movement is a functional task that challenges balance and
      co-ordination. There is a paucity of literature investigating the phases of this
      movement and its significance in a clinical rehabilitation context. Measuring
      phases of this movement may provide clinically applicable data for screening
      subjects for mobility problems and evaluating interventions. Fifty-six subjects
      from three groups; young (<65 years old), elderly (>65 years old) and elderly at
      risk of falling (EARF), performed the STW movement freely from a chair. Switches
      placed on the backrest, chair seat and two on the floor identified the times of
      movement events: onset, seat-off, swing-off and stance-off. These events defined
      three phases: flexion, extension and stance. Timing of events and phase duration
      data derived from this switch system were correlated with those taken from a
      three-dimensional motion analysis system. All switch events closely matched the
      motion analysis events with ICC (model 2.1) scores ranging from 0.93 to 1.00.
      Duration of all STW phases were statistically longer in the EARF group compared
      to both unimpaired groups (p<0.05). Data from the four switch configuration
      demonstrated excellent concurrent validity when associated with data from a three
      dimensional motion analysis system in identifying the phases of STW. Measurement
      of the phases of the STW task has potential in screening those at risk of falling
      and informing care strategies to prevent falls.

PMID- 16908154
TI  - Hydrogen sulfide: clandestine microbial messenger?
AB  - Although the toxicity of hydrogen sulfide (H(2)S) has been substantiated for
      almost 230 years, its pivotal roles in both aerobic and anaerobic organisms have
      only recently become evident. In low oxygen environments with millimolar
      concentrations of H(2)S, it functions as an electron donor and as an energy
      source in some systems. At micromolar levels, intracellular H(2)S in aerobic
      organisms has a vital role in redox balancing. At even lower concentrations,
      H(2)S provides essential signals in yeast, in the brain and in smooth and cardiac
      muscles. Here, other possible coordinating roles within and between
      microorganisms are suggested, including the possibility that H(2)S functions as a
      signalling mediator in prokaryotes. It is expected that future research will
      uncover a host of novel functions, not only in eukaryotes but also in prokaryotic
      species.

PMID- 16908156
TI  - Defensin: a multifunctional molecule lives up to its versatile name.
AB  - Human neutrophil proteins 1, 2 and 3 (HNP1-3) were originally identified as
      endogenous antibiotics that can kill microbial pathogens immediately after the
      onset of the host innate immune response. Recent studies revealed that these
      peptides perform additional, previously unexpected functions, notably the
      neutralization of certain secreted bacterial toxins. In this Opinion article, a
      brief overview of the well-established functions of HNP1-3 is given and novel
      biological activities of HNP1-3 are described, with emphasis on neutralization of
      secreted bacterial toxins. We propose that toxin neutralization represents a
      novel biological function of HNP1-3 in host defense.

PMID- 16908155
TI  - The evolving story of the omega subunit of bacterial RNA polymerase.
AB  - Omega (omega) is the smallest subunit of bacterial RNA polymerase (RNAP).
      Although identified early in RNAP research, its function remained ambiguous and
      shrouded by controversy for a considerable period. It has subsequently been shown
      that the protein has a structural role in maintenance of the conformation of the
      largest subunit, beta', and recruitment of beta' to the enzyme assembly.
      Conservation of this function across all forms of life indicates the importance
      of its role. Several recent observations have suggested additional functional
      roles for this protein and have settled some long-standing controversies
      surrounding it. In this context, revisiting the omega subunit story is especially
      interesting; here, we review the progress of omega research since its discovery
      and highlight the importance of these recent observations.

PMID- 16908157
TI  - Clinical outcome of severe head injury using three different ICP and CPP protocol
      driven therapies.
AB  - In the past 5 years, cerebral perfusion pressure (CPP) management has become the
      standard in the treatment of severe head injuries. Guidelines published in 2000
      suggest that CPP should be at least 70 mmHg; however, there is still debate about
      the optimal CPP. The purpose of the present study was to evaluate the
      effectiveness of these three widely used therapies: (i) intracranial pressure
      (ICP) targeted; (ii) CPP-targeted with CPP >70 mmHg; and (iii) modified CPP
      targeted (mCPP) therapy with CPP >60 mmHg. The clinical procedures, complications
      and outcomes of patients in the different groups were compared. Data, including
      patient age, sex, initial Glasgow Coma Scale, ICP, CPP, fluid status, amount of
      mannitol and vasopressor used, daily fluid intake and output, complications and
      clinical results, were collected from 213 patients with severe head injuries over
      a 12-year period. Patients were categorized into three groups (ICP, CPP, mCPP)
      according to the treatment protocol used. Retrospective data collection was
      performed by chart review. The mortality rate was 28.6%, 14.3% and 13.5% in the
      ICP, CPP, and mCPP groups, respectively. Highest intake/output ratio, amount of
      vasopressor used and pulmonary complications were seen in the CPP patients. The
      mCPP patients showed the best clinical outcome and lowest complication rate.
      Although CPP-targeted therapy is the most recommended therapeutic protocol, our
      data show that patients treated with modified CPP-target therapy with CPP >60
      mmHg have better clinical outcomes and fewer complications.

PMID- 16908158
TI  - Survival of glioblastoma patients related to presenting symptoms, brain site and
      treatment variables.
AB  - This retrospective study of 133 patients with glioblastoma multiforme evaluates
      survival times post-radiation in patients stratified in respect to age,
      presenting symptoms, tumour location, extent of surgery, and radiation dose
      delivered. Presenting features were coded as seizure, loss of consciousness,
      headache, speech or visual disturbance, weakness and confusion, as were tumour
      sites within the brain. Other parameters assessed included side of brain, age,
      extent of surgery and radiation dose. Statistical evaluation was undertaken by
      univariate and multivariate analyses to identify factors leading to enhanced
      survival. The median survival post-radiation was 10 months. A trend to improved
      early survival was demonstrated in patients presenting with acute and
      debilitating symptoms. The data presented reveals improved outcomes for patients
      younger than 60 years, particularly if radical surgery is undertaken with higher
      dose radiation. It is postulated that patients presenting with acute signs and
      symptoms are investigated earlier and are referred more promptly for treatment.

PMID- 16908159
TI  - Clinical application of transcranial Doppler monitoring for embolic signals.
AB  - A major advantage of transcranial ultrasound is its suitability for continuous
      monitoring. Microembolic signals (MES) are brief, high-intensity transients that
      occur when particulate microemboli or gaseous microbubbles pass through the
      ultrasound beam. These MES have been detected in several clinical scenarios, but
      rarely in age-matched controls. The detection of MES provides important
      pathophysiological information in a variety of disorders, but their clinical
      importance and possible therapeutic implications are still under debate. The
      present article summarizes the significance of MES in different clinical settings
      and outlines some of the problems to be resolved so that transcranial ultrasound
      can be applied in clinical practice.

PMID- 16908160
TI  - FXR, a multipurpose nuclear receptor.
AB  - The farnesoid X receptor (FXR) is a ligand-activated transcription factor and a
      member of the nuclear receptor superfamily. In the past six years, remarkable
      inroads have been made into determining the functional importance of FXR. This
      receptor has been shown to have crucial roles in controlling bile acid
      homeostasis, lipoprotein and glucose metabolism, hepatic regeneration, intestinal
      bacterial growth and the response to hepatotoxins. Thus, the development of FXR
      agonists might prove useful for the treatment of diabetes, cholesterol
      gallstones, and hepatic and intestinal toxicity.

PMID- 16908161
TI  - Bioactivity of glycogen phosphorylase inhibitors that bind to the purine
      nucleoside site.
AB  - The bioactivity in hepatocytes of glycogen phosphorylase inhibitors that bind to
      the active site, the allosteric activator site and the indole carboxamide site
      has been described. However, the pharmacological potential of the purine
      nucleoside inhibitor site has remained unexplored. We report the chemical
      synthesis and bioactivity in hepatocytes of four new olefin derivatives of
      flavopiridol (1-4) that bind to the purine site. Flavopiridol and 1-4
      counteracted the activation of phosphorylase in hepatocytes caused by AICAR (5
      aminoimidazole-4-carboxamide 1-beta-D-ribofuranoside), which is metabolised to an
      AMP analogue. Unlike an indole carboxamide inhibitor, the analogues 1 and 4
      suppressed the basal rate of glycogenolysis in hepatocytes by allosteric
      inhibition rather than by inactivation of phosphorylase, and accordingly caused
      negligible stimulation of glycogen synthesis. However, they counteracted the
      stimulation of glycogenolysis by dibutyryl cAMP by both allosteric inhibition and
      inactivation of phosphorylase. Cumulatively, the results show key differences
      between purine site and indole carboxamide site inhibitors in terms of (i)
      relative roles of dephosphorylation of phosphorylase-a as compared with
      allosteric inhibition, (ii) counteraction of the efficacy of the inhibitors on
      glycogenolysis by dibutyryl-cAMP and (iii) stimulation of glycogen synthesis.

PMID- 16908163
TI  - 2-Deoxy-2,3-didehydro-N-acetylneuraminic acid analogues structurally modified at
      the C-4 position: synthesis and biological evaluation as inhibitors of human
      parainfluenza virus type 1.
AB  - To explore the influence of binding to human parainfluenza virus type 1 (hPIV-1),
      a series of 4-O-substituted Neu5Ac2en derivatives 6a-e was synthesized and tested
      for their ability to inhibit hPIV-1 sialidase. Among compounds 6a-e, the 4-O
      ethyl-Neu5Ac2en derivative 6b showed the most potent inhibitory activity (IC50
      6.3 microM) against hPIV-1 sialidase.

PMID- 16908162
TI  - Synthesis and preliminary biological evaluation of beta-carotene and retinoic
      acid oxidation products.
AB  - Synthesis of the beta-carotene oxidation product, 2,3-dihydro-5,8-endoperoxy-beta
      apo-carotene-13-one (1) was achieved in six steps starting from beta-ionone.
      Photo-oxygenation of all trans-retinoic acid (8) and 13-cis-retinoic acid (9)
      produced a mixture of 5S*,8S*-epidioxy-5,8-dihydroretinoic acid (10) and 13-cis
      5S*,8S*-epidioxy-5,8-dihydroretinoic acid (11). Methylation of the crude photo
      oxygenation mixture afforded the corresponding methyl esters 12 and 13,
      respectively, both of which underwent ready aerial oxidation yielding hitherto
      unknown oxidation products of retinoic acid identified as methyl 5S*,8S*-epidioxy
      9,10beta-epoxy-5,8,9,10-tetrahydroretinoate (14) and methyl 13-cis-5S*,8S*
      epidioxy-9,10beta-epoxy-5,8,9,10-tetrahydroretinoate (15). Evaluation of 1, all
      trans-retinoic acid (8), 13-cis-retinoic acid (9), and the photo-oxygenation
      products 10-15 in a panel of five cancer cell lines showed 1 to be inactive and
      that 11 is significantly cytotoxic compared with the other retinoic acid analogs
      suggesting the requirement of the carboxylic acid moiety and the cis-geometry of
      the 13(14) double bond for cytotoxic activity.

PMID- 16908164
TI  - Synthesis and trypanocidal activity of 1,4-bis-(3,4,5-trimethoxy-phenyl)-1,4
      butanediol and 1,4-bis-(3,4-dimethoxyphenyl)-1,4-butanediol.
AB  - Chagas' disease is endemic in Central and South American countries. Specific
      chemotherapy with nifurtimox or benznidazole has been recommended for treatment
      of recent infection but they have limited efficacy. The natural products
      veraguensin (1) and grandisin (2) have shown potent in vitro activity against
      trypomastigote parasite (Y strain) with IC(50) 2.3 microM (1) and 3.7 microM (2).
      We report herein the synthesis and in vitro trypanocidal evaluation of
      symmetrical and unsymmetrical 1,4-diaryl-1,4-diol derivatives as potential
      trypanocidal analogs of natural compounds 1 and 2. Among the synthesized
      products, compounds 1,4-bis-(3,4,5-trimethoxyphenyl)-1,4-butanediol (6a) and 1,4
      bis-(3,4-dimethoxyphenyl)-1,4-butanediol (6b) showed better activity against
      Trypanosoma cruzi trypomastigotes with IC(50) 100 and 105 microM (Y strain),
      respectively, and 110 microM (Bolivia strain) for both compounds. However, the
      most active compound of this series was 1,4-bis-(3,4-dimethoxyphenyl)butane-1,4
      dione (7b) with IC(50) 10 and 200 microM against Y and Bolivia strains,
      respectively.

PMID- 16908165
TI  - Delivery of 2-5A cargo into living cells using the Tat cell penetrating peptide:
      2-5A-tat.
AB  - 2',5'-Oligoadenylate tetramer (2-5A) has been chemically conjugated to short HIV
      1 Tat peptides to provide 2-5A-tat chimeras. Two different convergent synthetic
      approaches have been employed to provide such 2-5A-tat bioconjugates. One
      involved generation of a bioconjugate through reaction of a cysteine terminated
      Tat peptide with a alpha-chloroacetyl derivative of 2-5A. The second synthetic
      strategy was based upon a cycloaddition reaction of an azide derivative of 2-5A
      with a Tat peptide bearing an alkyne function. Either bioconjugate of 2-5A-tat
      was able to activate human RNase L. The union of 2-5A and Tat peptide provided an
      RNase L-active chimeric nucleopeptide with the ability to be taken up by cells by
      virtue of the Tat peptide and to activate RNase L in intact cells. This strategy
      provides a valuable vehicle for the entry of the charged 2-5A molecule into cells
      and may provide a means for targeted destruction of HIV RNA in vivo.

PMID- 16908166
TI  - QSAR modeling of anti-invasive activity of organic compounds using structural
      descriptors.
AB  - The anti-invasive activity of 139 compounds was correlated by an artificial
      neural network approach with descriptors calculated solely from the molecular
      structures using CODESSA Pro. The best multilinear regression method implemented
      in CODESSA Pro was used for a pre-selection of descriptors. The resulting
      nonlinear (artificial neural network) QSAR model predicted the exact class for 66
      (71%) of the training set of 93 compounds and 32 (70%) of validation set of 46
      compounds. The standard deviation ratios for the both training and validation
      sets are less than unity, indicating a satisfactory predictive capability for
      classification of the nature of the anti-invasive activity data. The proposed
      model can be used for the prediction of the anti-invasive activity of novel
      classes of compounds enabling a virtual screening of large databases of
      anticancer drugs.

PMID- 16908167
TI  - Phenylethanoid oligoglycosides and acylated oligosugars with vasorelaxant
      activity from Cistanche tubulosa.
AB  - The methanolic extract from the dried stems of Cistanche tubulosa (Schrenk) R.
      Wight was found to show an inhibitory effect on contractions induced by
      noradrenaline in isolated rat aortic strips. From the extract, new phenylethanoid
      oligoglycoside constituents, kankanosides F and G, and an acylated oligosugar,
      kankanose, were isolated together with 14 known compounds. The structures of
      these new compounds were determined on the basis of their chemical and
      physicochemical evidence. In addition, principal constituents, kankanoside F,
      kankanose, echinacoside, acteoside, and cistanoside F, showed vasorelaxant
      activity, and several structural requirements for the activity were clarified.

PMID- 16908168
TI  - Biotinylated biphenyl ketone-containing 2,4-dioxobutanoic acids designed as HIV-1
      integrase photoaffinity ligands.
AB  - The diketo acid (DKA) class of HIV-1 integrase inhibitors are thought to function
      by chelating divalent metal ions within the enzyme catalytic center. However,
      differences in mutations conferring resistance among sub-families of DKA
      inhibitors suggest that multiple binding orientations may exist. In order to
      facilitate identification of DKA-binding sites, biotin-tagged biphenyl ketone
      containing 2,4-dioxobutanoic acids were prepared as DKA photoaffinity probes.
      Introduction of biotin was obtained by means of Huisgen [3+2] cycloaddition
      'click chemistry.' Two photoprobes, 5a and 5b, were prepared bearing short and
      long linker segments, respectively, between the biotin and DKA nucleus. The
      greatest inhibitory potency was shown by 5b, which inhibited 3'-processing and
      strand transfer reactions with IC50 values of > 333 microM and 12.4 microM,
      respectively. In cross-linking assays designed to measure disruption of substrate
      DNA binding, the photoprobes behaved similarly to a reference DKA inhibitor.
      Analogues 5a and 5b represent novel photoaffinity ligands, which may be useful in
      clarifying the HIV-1 binding interactions of DKA inhibitors.

PMID- 16908169
TI  - Synthesis and receptor binding studies of halogenated N,N-dialkylel-(2-phenyl-1H
      indol-3-yl)glyoxylamides to visualize peripheral benzodiazepine receptors with
      SPECT or PET.
AB  - A library of halogenated 2-arylindolyl-3-oxocarboxamides was prepared to develop
      radioligands to visualize cerebral PBR by SPECT and PET imaging. In vitro
      evaluation showed that most of the synthesized compounds were selective,high
      affinity PBR ligands with adequate lipophilicity (log D7.4 in the range of 1.6
      2.4). The iodinated derivative 11 (Ki = 2.6 nM) and the fluorinated analog 26 (Ki
      = 6.2 nM) displayed higher affinity than reference compounds.

PMID- 16908170
TI  - Structure-activity relationships in platelet-activating factor. Part 14:
      synthesis and biological evaluation of piperazine derivatives with dual anti-PAF
      and anti-HIV-1 activity.
AB  - As HIV-associated dementia prevalence has risen with the lifespan of HIV-infected
      individuals, there is an important need for antiretroviral and anti-inflammatory
      drugs targeting the central nervous system. Platelet-activating factor, a
      mediator of inflammation, is an HIV-induced neurotoxin secreted in the infected
      brain. In this work, we developed piperazine derivatives bearing a heterocyclic
      moiety as PAF-antagonists and HIV-1 replication inhibitors with micromolar
      potency.

PMID- 16908172
TI  - Synthesis and evaluation of a 3-position diastereomer of 1alpha,25-dihydroxy
      2beta-(3-hydroxypropoxy)vitamin D3 (ED-71).
AB  - A 3-position diastereomer of 1alpha,25-dihydroxy-2beta-(3-hydroxypropoxy)vitamin
      D3 (ED-71, 2), 3-epi-ED-71 (4), was synthesized by the convergent method coupling
      the A-ring fragment (5) with the C/D-ring fragment (6). As the results of
      preliminary in vitro biological evaluation of 3-epi-ED-71 (4), the inhibition of
      parathyroid hormone secretion in bovine parathyroid cells and binding affinity to
      human recombinant vitamin D receptor and to human vitamin D binding protein in
      comparison with ED-71 (2), 1alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3, 1), and 3
      epi-1,25(OH)2D3 (3) are described.

PMID- 16908171
TI  - Synthesis and evaluation of novel 8,5-fused bicyclic peptidomimetic compounds as
      interleukin-1beta converting enzyme (ICE) inhibitors.
AB  - An 8,5-fused bicyclic peptidomimetic ring system generated by a stereoselective
      ring metathesis reaction was elaborated into potent inhibitors of interleukin
      1beta converting enzyme (ICE, caspase-1). Multiple compounds were found that
      exhibited ICE IC50 values < 10 nM and were selective over caspase-3 and caspase
      8. These active analogs generally possessed good activity (IC50 values < 100 nM)
      in a whole cell assay measuring IL-1beta production. Pharmacokinetic analysis of
      the ethyl acetal prodrug form of a selected active lead revealed a compound with
      a reasonable plasma half-life (1.1 h) and good oral bioavailability (30%).

PMID- 16908173
TI  - Synthesis and immunosuppressive activity of new artemisinin derivatives. Part 2:
      2-[12(beta or alpha)-dihydroartemisinoxymethyl(or 1'-ethyl)]phenoxyl propionic
      acids and esters.
AB  - Another series of novel dihydroartemisinin derivatives were synthesized and
      assessed for their cytotoxicity of lymphocyte, inhibitory activity on mitogen
      induced spleen lymphocyte proliferation in vitro. Some of the compounds exhibited
      inhibitory effects on ConA-induced T cell and LPS-induced B cell proliferation
      comparable to or more potent than parent artemisinin.

PMID- 16908174
TI  - Synthesis and antitumor activity of CBI-bearing ester and carbamate prodrugs of
      CC-1065 analogue.
AB  - Prodrugs of a CBI-bearing CC-1065 analogue were synthesized. Antitumor activity
      of the compounds was evaluated against tumor cells in vitro and in mouse tumor
      models. Compounds 1 and 7, bearing methylpiperazine and DHA moieties,
      respectively, showed significant antitumor activity in both the L1210 leukemia
      and Lewis lung carcinoma mouse tumor models. For the carbamate prodrugs 1-4 and
      6, there is a good correlation between the drug's potency both in vitro and in
      animal tumor models; however, there is no correlation between the prodrug's
      antitumor activity and the type of bonds linking the free drug. There are no
      significant differences between the antitumor activities of those that can or
      cannot be protonated at physiological pH. Compounds 6 and 7, each bearing a DHA
      moiety, did not show significantly improved antitumor activity compared to other
      prodrugs bearing DHA moieties, suggesting that DHA may not be used universally to
      significantly improve a drug's antitumor efficacy.

PMID- 16908175
TI  - Design, synthesis, and biological evaluation of substituted 2,3-dihydro-1H
      cyclopenta[b]quinolin-9-ylamine related compounds as fructose-1,6-bisphosphatase
      inhibitors.
AB  - In a search for structurally new inhibitors of fructose-1,6-bisphosphatase
      (F16BPase), substituted 2,3-dihydro-1H-cyclopenta[b]quinoline derivatives were
      synthesized. It has been shown that the 2,3-dihydro-1H-cyclopenta[b]quinoline
      moiety may represent a suitable scaffold for the synthesis of potent F16BPase
      inhibitors endowed with significantly lower EGFR tyrosine kinase inhibitory
      activity.

PMID- 16908176
TI  - Walsh filters for tailoring of resolution in microscopic imaging.
AB  - Walsh functions form a complete set of normal orthogonal functions that take on
      values either +1 or -1 over a prespecified domain. Corresponding filters can be
      synthesized as phase filters that take on values either 0 or pi phase. This paper
      presents different types of Walsh functions in one and two dimensions to
      demonstrate that a large class of pupil filters can be synthesized from them to
      cater to the various needs of diffraction pattern for tailoring transverse and/or
      axial resolution in microscopic applications. Illustrative numerical results are
      presented.

PMID- 16908177
TI  - Target preparation by the precipitation method for nuclear reactions.
AB  - A technique for preparing nuclear reaction targets of various thicknesses was
      developed by using common filtration technique of hydroxide precipitates with a
      porous Al(2)O(3) membrane filter. Uniformity was found to be within a few % in
      each thickness. Durability for beam irradiation was also confirmed. The
      preparation procedure is convenient and the method is appropriate for several
      target materials, including not only precious materials but also radioactive
      materials with low contamination.

PMID- 16908178
TI  - Characterization of human epidermal growth factor in human serum and urine under
      native conditions.
AB  - The objective of this study was to investigate the molecular nature of the human
      epidermal growth factor (EGF) in serum and urine samples of normal subjects.
      Recombinant EGF emerged as a single peak and did not interact with human IgG1 and
      albumin up to the concentration of 12 microg/ml. Freshly separated human serum
      contained only trace amounts of EGF. However, EGF appeared and increased in serum
      separated from blood after spontaneous overnight clotting. The authentic 6 kDa
      form of EGF made up nearly 40% of the total EGF in serum and revealed relatively
      homogeneous feature. The remaining immunoreactive fractions corresponded to 160
      kDa proEGF. Immunoreactive EGF in blood seemed to be associated with the EGF
      release from platelets. TSKgel G3000SW chromatography of freshly-voided morning
      and day urines revealed that urine samples mainly contained two major form of
      EGF; a high-molecular-weight (HMW) and low-molecular-weight (LMW) forms. In the
      sense of molecular nature of EGF contents, morning urine was more heterogeneous
      than day urine of the same individuals. The LMW form of EGF in morning urine, in
      which its proportion was more than 90% of the total EGF, revealed further
      heterogeneous feature generally containing three to four different components.

PMID- 16908179
TI  - Tissue microarray analysis of interleukin-20 expression.
AB  - Knowledge about the biological functions and clinical implications of interleukin
      (IL)-20, a recently discovered cytokine in the IL-10 family, is still incomplete.
      Our aim was to determine the distribution of IL-20 expression and to delineate
      the cell types that express IL-20 in healthy and neoplastic tissue, because this
      information will significantly affect the exploration of its pathophysiological
      roles. We used tissue microarray technology and an immunohistochemical survey
      using an anti-IL-20 monoclonal antibody to examine IL-20 expression in 36 non
      neoplastic and 14 neoplastic tissues. IL-20 protein was positively stained in 30
      non-neoplastic tissue types and five major cell types: epithelial cells,
      myoepithelial cells, endothelial cells, macrophages, and skeletal muscle cells.
      We also found that several types of tumor cells stained positive for IL-20,
      especially in squamous cell carcinoma of the skin, tongue, esophagus, and lung.
      Our data provide valuable references for further investigation of the biological
      functions and clinical implications of IL-20 in humans.

PMID- 16908180
TI  - Association of VEGF genetic polymorphisms with prostate carcinoma risk and
      clinical outcome.
AB  - OBJECTIVES: Vascular endothelial growth factor (VEGF) is a potent stimulus of
      angiogenesis that has an important role in many human malignancies including
      prostate carcinoma (PCa). We evaluated the role of the functional VEGF
      polymorphisms as genetic markers for PCa susceptibility and prognosis. METHODS:
      The study included 101 patients with PCa and [corrected] 100 age-matched healthy
      men. The VEGF genotypes -1154G>A were identified by allele-specific polymerase
      chain reaction (AS-PCR) and the genotypes -634G>C and 936C>T were identified by
      restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR).
      RESULTS: A negative association was found between VEGF -1154AA genotype and PCa
      risk (OR=0.27; P=0.009). Furthermore, the presence of the VEGF -1154A allele
      appeared to be associated with a decreased [corrected] risk of higher tumor grade
      (OR=0.37; P=0.01). A significant increased risk of prostate cancer was associated
      with the VEGF -634 (GC+CC) combined genotype (OR=1.95; P=0.02). The VEGF -634C
      allele was associated with the aggressive phenotype of prostate cancer as defined
      by the high histological grade (OR=3.48; P=0.007). The VEGF -1154A/-634G
      haplotype was negatively associated with PCa risk (OR=0.48; P=0.005) and high
      tumor grade compared to low grade (OR=0.37; P=0.02). CONCLUSIONS: Genetic
      variations in the VEGF may predict not only PCa risk but also tumor
      aggressiveness.

PMID- 16908181
TI  - 3-Hydroxycoumarin as a new matrix for matrix-assisted laser desorption/ionization
      time-of-flight mass spectrometry of DNA.
AB  - 3-Hydroxycoumarin (3-HC) was designed, synthesized, and tested as a matrix for
      matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
      (MALDI-TOF MS) analyses of a variety of synthetic oligodeoxynucleotides ranging
      long from three to 70 bases. Using the matrix solution of 3-HC dissolved in a
      mixed solvent of acetone and diammonium hydrogen citrate, DNA segments over the
      mass range 800 Da to 6900 Da were isotopically resolved with high signal-to-noise
      (S/N) ratio. The individual isotopic molecular ion peaks of a group of 23-mer
      mixed-base oligomers differing by one or two bases with mass differences of 9 or
      7 Da were recorded. Larger oligodeoxynucleotide segments of 34-mer, 50-mer, and
      70-mer have also been analyzed effectively. Less than 250 attomol of a 10-mer DNA
      segment was clearly detected without any fragmentation. The new matrix can be
      used for the analysis of DNA segments in both positive- and negative-ion modes,
      and the quality of all negative-ion mode spectra are as good as that obtained in
      positive-ion mode shown in this paper. Compared with conventional matrices of 3
      hydroxypicolinic acid (3-HPA) and 6-aza-2-thiothymine (ATT), 3-HC had noticeable
      improvement in resolution, S/N ratio, spot-to-spot-, and sample-to-sample
      reproducibility for analyzed DNA segments.

PMID- 16908182
TI  - The MAX-interacting transcription factor network.
AB  - The small bHLHZip protein MAX functions at the center of a transcription factor
      network that governs many aspects of cell behavior, including cell proliferation
      and tumorigenesis. MAX serves as a cofactor for DNA binding by the various
      members of this network, which include the MYC family of oncoproteins and a group
      of putative MYC antagonists that include MNT, MXD1-4 (formerly MAD1, MXI1, MAD3
      and MAD4) and MGA. The many heterodimerization partners of MAX raises questions
      concerning the dynamics of MAX interactions and the functional consequences of
      the switching of Max partners. Here we review the activities of MAX, its
      interaction partners, and recent results showing that tissues lacking the MAX
      interacting protein MNT are predisposed to tumor formation.

PMID- 16908183
TI  - Analyzing protein kinase dynamics in living cells with FRET reporters.
AB  - Genetically encoded reporters based on fluorescence resonance energy transfer
      (FRET) are being developed for analyzing spatiotemporal dynamics of kinase
      activities in living cells, as the activities of this class of enzymes are often
      dynamically regulated and spatially compartmentalized within specific signaling
      context. Here we describe a general modular design and engineering strategies for
      the development of activity reporters for kinases of interest, using A-kinase
      activity reporter (AKAR) as an illustrative example. Discussed here are basic
      structure of such reporters, design considerations, reporter gene construction,
      cellular and in vitro characterization. Strategies for improving specificity,
      dynamic range or sensitivity, reversibility and integrity of the reporter as well
      as basic methods for live-cell time-lapse imaging using these reporters are
      summarized. Discussion of using this approach in the study of MAPK cascades is
      also provided. These FRET-based kinase activity reporters, along with analogous
      probes based on alternative designs, provide real-time tracking of kinase
      dynamics with subcellular resolution, which should complement other methods and
      offer great opportunities to delineate the molecular mechanisms underlying the
      complex regulation of kinases.

PMID- 16908184
TI  - Expression and characterization of MAP kinases in bacteria.
AB  - Mitogen-activated protein kinases (MAPKs) are common signal transducers in all
      eukaryotic organisms. MAPKs are activated by protein kinase cascades consisting
      of MAPK kinases (MAP2Ks) and MAPK kinase kinases (MAP3Ks). Extracellular-signal
      regulated kinases 1 and 2 (ERK1/2) are the best characterized MAPKs. Like other
      MAPKs their activity is regulated by dual phosphorylation as well as
      dephosphorylation by a host of phosphoprotein phosphatases. The ability to
      phosphorylate or thiophosphorylate ERK2 in vitro, as described here, is valuable
      for use in downstream applications designed to investigate MAPK signaling
      networks.

PMID- 16908185
TI  - Using peptide arrays to define nuclear carrier binding sites on nucleoporins.
AB  - In the peptide SPOT array technique, an array of different peptides are
      synthesized on, and covalently linked to, cellulose membranes. In one usage of
      this technique, these peptides are screened in an overlay assay to determine
      which short sequence(s) contains a binding site for an interacting protein. By
      preparing overlapping peptides that cover the entire sequence of a protein, all
      of the binding domains on the protein for a second protein can be identified. We
      have utilized the peptide SPOT array technique to identify the short amino acid
      sequences within nuclear pore complex proteins (also known as nucleoporins or
      Nups) that bind the nuclear carrier importin-beta. Crystallization studies by
      others have indicated that nuclear carriers such as importin-beta bind to
      phenylalanine-glycine (FG) repeats present in numerous copies in the sequences of
      a family of nucleoporins. Consistent with this, we found that most (but not all)
      of the Nup binding sites for importin-beta identified by this technique contain
      Fx, FG, FxFG, FxFx, or GLFG sequences, although not all such sequences bound
      importin-beta. Peptide SPOT array substitution studies confirmed a crucial role
      for the phenylalanine in FG repeats and identified a lysine residue flanking some
      repeats that is crucial for importin-beta binding to those repeats. In addition
      to these expected binding sequences for importin-beta, we found multiple
      instances of a peptide lacking a canonical FG repeat that strongly bound importin
      beta, indicating that additional Nup sequences may form binding sites for
      importin-beta.

PMID- 16908186
TI  - Cloning, expression and rapid purification of active recombinant mycothiol ligase
      as B1 immunoglobulin binding domain of streptococcal protein G, glutathione-S
      transferase and maltose binding protein fusion proteins in Mycobacterium
      smegmatis.
AB  - Mycothiol ligase (MshC) is a key enzyme in the biosynthesis of mycothiol, a small
      molecular weight thiol found in Mycobacteria spp. and other actinomycetes.
      Mycothiol plays a fundamental role in these organisms by helping to provide
      protection from the effects of reactive oxygen species and electrophiles,
      including many antibiotics. It has recently been demonstrated that the MshC gene
      and more generally the production of mycothiol are essential to Mycobacterium
      tuberculosis, indicating that MshC may represent a novel target for new classes
      of antituberculars. Because MshC cannot be expressed heterologously in
      Escherichia coli and isolation from Mycobacterium smegmatis is impractical, we
      have optimized the E. coli-M. smegmatis shuttle vector pACE for cloning and
      recombinant expression of MshC (under control of an acetamidase-inducible
      promoter). To improve expression levels and simplify purification, we further
      constructed three N-terminal-MshC fusion proteins where N-terminal tags included
      the B1 domain of streptococcal protein G (to give GB1-MshC), glutathione-S
      transferase (to give GST-MshC) and maltose binding protein (to give MBP-MshC),
      for expression in M. smegmatis. By expressing all three fusion proteins in a
      mutant strain of M. smegmatis mc(2)155, namely I64 L205P MshC M. smegmatis which
      lacks mycothiol ligase activity, we demonstrate in vivo mycothiol ligase activity
      for each construct. Recombinant GST-MshC and MBP-MshC were isolated in one step
      by affinity chromatography in a yield of 0.7 and 1.2 mg fusion protein/L and
      exhibited specific activities of 9 nmolmin(-1)mg(-1) and 25 nmolmin(-1)mg(-1),
      respectively.

PMID- 16908187
TI  - Functional expression and purification of recombinant Tx1, a sodium channel
      blocker neurotoxin from the venom of the Brazilian "armed" spider, Phoneutria
      nigriventer.
AB  - Tx1 from the venom of the Brazilian spider, Phoneutria nigriventer, is a lethal
      neurotoxic polypeptide of M(r) 8600 Da with 14 cysteine residues. It is a novel
      sodium channel blocker which reversibly inhibits sodium currents in CHO cells
      expressing recombinant sodium (Nav1.2) channels. We cloned and expressed the Tx1
      toxin as a thioredoxin fusion product in the cytoplasm of Escherichia coli. After
      semipurification by immobilized Ni-ion affinity chromatography, the recombinant
      Tx1 was purified by reverse phase chromatography and characterized. It displayed
      similar biochemical and pharmacological properties to the native toxin, and it
      should be useful for further investigation of structure-function relationship of
      Na channels.

PMID- 16908188
TI  - A novel lysozyme from Xanthomonas oryzae phage varphiXo411 active against
      Xanthomonas and Stenotrophomonas.
AB  - In this study, a bacteriophage of Xanthomonas oryzae pv. oryzae designated as
      varphiXo411 was isolated. Random sequencing of its genome revealed that it is
      closely related to another X. oryzae phage, Xp10. A cloned fragment carries the
      lysozyme gene, lys411. The deduced protein, Lys411, shares 92% identity with Xp10
      lysozyme, which contains an extra 46 aa at the N-terminus. Lys411 shows over 40%
      identities to several other phage lysozymes. The His-tagged protein, Lys411H,
      expressed in Escherichia coli largely formed as inclusion bodies. The insoluble
      protein was solubilized in urea and purified by passing through a His-bind
      column, and the lytic activity was then restored by a refolding process. The
      optimal assay conditions determined for Lys411H are in 0.1M potassium phosphate
      buffer, pH 6.6 containing 1 mM CuCl(2) at 25 degrees C. Lysis assays using
      different bacterial cells as the substrates indicate that Lys411H is the first
      lysozyme active against both Xanthomonas and Stenotrophomonas maltophilia. This
      suggests that Lys411 can be a candidate to be developed into a therapeutic agent
      for treating S. maltophilia infections, in addition to the potential use in
      control of the plant diseases caused by Xanthomonas. By analogy to the situation
      in Xp10, we predict that varphiXo411 has no holin, the protein required for
      lysozyme export, and the N-terminal signal-arrest-release sequence of Lys411 can
      accommodate its own export to the periplasm.

PMID- 16908189
TI  - A kinetically trapped intermediate of FK506 binding protein forms in vitro:
      chaperone machinery dominates protein folding in vivo.
AB  - We have characterised the stability, binding and enzymatic properties of three
      human FK506 binding proteins (FKBP-12) differing only by the length and sequence
      of their N-terminus. One construct has a short hexa-his tag (6H-FKBP12); the
      second longer fusion protein (6HL-FKBP12) contains an additional thrombin
      protease cleavage site; the third has the long fusion tag removed and is
      essentially native FKBP-12 (cFKBP12). The proteins were purified both under
      native conditions and also using a refolding protocol. All three natively
      purified proteins have, within experimental error, the same peptidyl-prolyl
      isomerase (PPIase) activity (k(cat)/K(m) approximately 1 x 10(6)M(-1)s(-1)), and
      bind a natural inhibitor, rapamycin, with the same high affinity (K(d)
      approximately 6 nM). However, refolding of the protein containing the longer tag
      in vitro results in reduced PPIase activity (the k(cat)/K(m) was reduced from 1 x
      10(6)M(-1)s(-1) to 0.81 x 10(6)M(-1)s(-1)) and a 6-fold affinity loss for
      rapamycin. Addition of both the long and short N-terminal his-tags slows the
      refolding kinetics of FKBP-12. However, the shorter his-tagged fusion protein
      regains fully native activity (> or =95%) while the longer regains only
      approximately 80-85% of native activity. Equilibrium urea denaturation
      titrations, isothermal titration calorimetry (ITC), analytical gel-filtration,
      and fluorescence binding data show that this loss of activity is not due to gross
      misfolding events, but is rather caused by the formation of a stable but subtly
      misfolded protein that has reduced peptidyl-prolyl isomerase (PPIase) activity
      and reduced affinity for rapamycin. The difference in behaviour between the in
      vitro refolded and native forms is due to the dominant role of the cellular
      chaperone/folding machinery.

PMID- 16908190
TI  - Improving purification of recombinant human interferon gamma expressed in
      Escherichia coli; effect of removal of impurity on the process yield.
AB  - Process development and optimization studies were performed in order to improve
      the purification process of (rhIFN-gamma). The objective was to generate material
      with higher purity and quantity. An in-process control screening was developed to
      obtain the optimal condition for column chromatographic purification by measuring
      LPS, nucleic acids, rhIFN- gamma, monomer and its covalent dimers. A new resin
      screening method was applied to select optimal resin for each of the
      chromatographic columns. The resulting process used Butyl and Q-Sepharose,
      refolding and SP-Sepharose for purification of IFN-gamma. Effects of different
      process conditions such as cell lysis, removal of impurity and oxygen
      concentration were evaluated. Removal of impurities was evaluated by washing of
      inclusion bodies with 1% Triton X-100 and 3M urea and different chromatography
      steps. The results reveal that Triton removed about 43% of the LPS but urea had
      no effect on removal of nucleic acids and LPS. Further analysis show that removal
      of impurities by column chromatography decreases aggregation and increases the
      process yield. Oxygen concentration was identified as parameter that could have a
      significant impact on covalent dimers formation, as an unacceptable
      pharmaceutical form of rhIFN-gamma. On the basis of small-scale studies, optimum
      operating conditions were chosen and the purification process was successfully
      scaled-up to a pilot scale process with step yield and product quality that were
      better than previous reports.

PMID- 16908191
TI  - Improved conditions for production of recombinant plant sesquiterpene synthases
      in Escherichia coli.
AB  - Amorpha-4,11-diene synthase (ADS) from Artemisia annua and (+)-germacrene
      synthase (GDS) from Zingiber officinale were expressed in Escherichia coli under
      different conditions to optimize the yield of active soluble protein. The cDNAs
      of these enzymes were inserted into the pET28 vector (Novagen) and expressed in
      four different bacterial strains; BL21 (DE3), BL21 (DE3) Tuner, BL21 (DE3) pLysS
      and BL21 (DE3) pLysS Tuner using different inducing agents (IPTG, The Inducer).
      The effects of induction under osmotic stress in the presence of glycine betaine
      and sorbitol were investigated. Although background expression for ADS was
      reduced when using pLysS strains, no significant difference was noted for ADS
      activity in soluble whole cell lysates after induction with either IPTG or The
      Inducer. For GDS, on the other hand, the change between BL21 (DE3) cells and BL21
      (DE3) Tuner, induced with IPTG, leads to a twofold increase in enzyme activity in
      the soluble fraction while a reduction in activity is observed when using the
      pLysS strains. The same doubling of activity is observed for GDS when the
      commonly used BL.21 (DE3) is induced with The Inducer. Addition of 2.5 mM glycine
      betaine and 660 mM sorbitol to the bacterial growth media resulted in reduction
      of growth rate and biomass yield but under these conditions the best overall
      protein production, for both enzymes, was obtained. Compared to the standard
      conditions previously used in our laboratory the yield of soluble active protein
      was increased 7- and 2.5-fold for ADS and GDS, using BL21 (DE3) pLysS Tuner and
      BL21 (DE3), respectively.

PMID- 16908192
TI  - Expression, purification and characterization of individual bromodomains from
      human Polybromo-1.
AB  - Computational analysis reveals six tandem bromodomains within the amino-terminal
      region of the human Polybromo-1 protein, a required subunit of the Polybromo,
      BRG1-associated factors chromatin remodeling complex. Bromodomains are acetyl
      lysine binding modules found in many chromatin binding proteins and histone
      acetyltransferases. Recent in vivo studies suggest that bromodomains can both
      discriminate the presence of an acetyl group on a lysine side chain and locate
      the acetyl-lysine within a histone protein. Together, this implies that multiple
      bromodomains may be able to function cooperatively and recognize a specific
      acetylation pattern to localize remodeling complexes to specific chromatin sites.
      Here, the cloning, expression and bioactivity of recombinant bromodomains from
      the human Polybromo-1 protein is described. Individual bromodomains from
      Polybromo-1 were cloned from human cDNA into a pET30b expression vector enabling
      effective one-step purification by affinity chromatography. Due to complications,
      including the high number of rare codons found in the coding regions and the
      tendency of individually expressed domains to aggregate and misfold, bacterial
      expression was only achieved using a cell strain containing rare eukaryotic
      tRNAs. Fluorescence-based bioactivity assays were performed to determine if
      native binding features were retained. The present cloning, expression, and
      purification procedure enabled the preparation of large quantity and high yields
      of biologically active recombinant bromodomains from human Polybromo-1 for in
      vitro structure and function studies. This is the first report of recombinant
      active form of bromodomains obtained from PB1.

PMID- 16908193
TI  - Structure determination of clathrin coats to subnanometer resolution by single
      particle cryo-electron microscopy.
AB  - Clathrin triskelions can assemble into lattices of different shapes, sizes and
      symmetries. For many years, the structures of clathrin lattices have been studied
      by single particle cryo-electron microscopy, which probed the architecture of the
      D6 hexagonal barrel clathrin coat at the molecular level. By introducing
      additional image processing steps we have recently produced a density map for the
      D6 barrel clathrin coat at subnanometer resolution, enabling us to generate an
      atomic model for this lattice [Fotin, A., Cheng, Y., Sliz, P., Grigorieff, N.,
      Harrison, S.C., Kirchhausen, T., Walz, T., 2004. Molecular model for a complete
      clathrin lattice from electron cryomicroscopy. Nature 432, 573-579]. We describe
      in detail here the image processing steps that we have added to produce a density
      map at this high resolution. These procedures should be generally applicable and
      may thus help determine the structures of other large protein assemblies to
      higher resolution by single particle cryo-electron microscopy.

PMID- 16908194
TI  - Automated segmentation of molecular subunits in electron cryomicroscopy density
      maps.
AB  - Electron cryomicroscopy (cryoEM) is capable of imaging large macromolecular
      machines composed of multiple components. However, it is currently only possible
      to achieve moderate resolution at which it may be possible to computationally
      extract the individual components in the machine. In this work, we present
      application details of an automated method for detecting and segmenting the
      components of a large machine in an experimentally determined density map. This
      method is applicable to object with and without symmetry and takes advantage of
      global and local symmetry axes if present. We have applied this segmentation
      algorithm to several cryoEM data sets already deposited in EMDB with various
      complexities, symmetries and resolutions and validated the results using manually
      segmented density and available structures of the components in the PDB. As such,
      automated segmentation could become a useful tool for the analysis of the ever
      increasing number of structures of macromolecular machines derived from cryoEM.

PMID- 16908195
TI  - Molecular cloning and expression analysis of a hepcidin antimicrobial peptide
      gene from turbot (Scophthalmus maximus).
AB  - Antimicrobial peptides (AMPs) are regarded as important components of the host
      innate immune system and play crucial roles in host defence against microbial
      invasion. A small number of hepcidin AMPs have been isolated from teleosts. Here,
      we report the isolation of a hepcidin gene from the liver of turbot (Scophthalmus
      maximus) (GenBank accession numbers: and ). In the 1037 bp-long genomic sequence,
      three exons and two introns were identified. The full-length cDNA is 778bp long
      and contains an ORF of 273bp encoding a prepropeptide of 90 amino acid residues.
      The predicted prepropeptide consists of three domains: a signal peptide (24 amino
      acids), a prodomain (40 amino acids) and a mature peptide (26 amino acids). RT
      PCR demonstrated that hepcidin transcripts were highly abundant in liver,
      abundant in heart, head kidney, spleen, skin and gill, less abundant in blood
      cell, gonad and intestine, and undetectable level in muscle. The level of the
      hepcidin mRNA in embryos gradually increases during embryogenesis from 2 h (2
      cell stage) to 95 h (larva stage) after fertilisation. Challenge of turbot with
      pathogenic bacteria, Listonella anguillarum, significantly elevated hepcidin mRNA
      levels in liver and spleen in a time-dependent fashion. The hepcidin transcripts
      were detected in turbot embryonic cell line (TEC). Challenge of TEC cells with
      the pathogenic bacteria significantly elevated hepcidin mRNA levels.

PMID- 16908196
TI  - In vitro effects of pure microcystin-LR on the lymphocyte proliferation in
      rainbow trout (Oncorhynchus mykiss).
AB  - The aim of this study was to determine the in vitro influence of microcystin-LR
      on the viability and mitogenic response of rainbow trout (Oncorhynchus mykiss)
      lymphocytes since few data are available in the literature on the influence of
      cyanotoxins on fish immunocompetent cells. Lymphocytes were isolated from blood
      and haematopoietic organs (pronephros and spleen) and cultivated in RPMI 1640
      medium with different concentrations of the toxin (1, 5, 10, 20, 40 mg ml-1 of
      cell suspension). Dose-dependent effects of microcystin-LR on the lymphocyte
      viability were shown. The lymphocyte proliferation was inhibited after
      application of microcystin at a concentration of 40 mg ml-1 but significantly
      increased at a concentration of 1mg ml-1 in comparison to the control group. The
      results suggest the modulatory effects of microcystin-LR dependent on the applied
      concentration.

PMID- 16908197
TI  - Repeatability of electromyography and force measurements of the neck muscles in
      adolescents with and without headache.
AB  - BACKGROUND: Reliable measurements are needed to study the dysfunction of the neck
      muscles. The aim of this study was to determine the intra-tester repeatability of
      EMG and isometric force measurements of the neck muscles in adolescents with
      headache and headache-free controls. METHODS: A group of 30 adolescents with
      migraine-type headache, 29 with tension-type headache, and 30 headache-free
      controls were recruited. Maximal isometric neck muscle force with simultaneous
      recording of surface EMG from the cervical erector spinae and the
      sternocleidomastoideus muscles was measured twice during one day. FINDINGS: For
      all groups, intra-class correlation coefficients (ICC) and coefficients of
      variation (CV) showed acceptable repeatability of all measurements. (Force
      measurements: ICC 0.98-0.99, CV 0.7-3.7%; EMG measurements: ICC 0.95-0.99, CV 4.9
      10.1%.) On the individual level, variation between the consecutive measurements
      was found to be low in all groups. INTERPRETATION: The present EMG and force
      measurements of neck muscles indicate acceptable intra-tester repeatability in
      adolescents. The repeatability was comparable in migraine- and tension-type
      headache and headache-free groups. The EMG and the force measurements offer the
      possibility to investigate neck muscle dysfunction in adolescent headache.

PMID- 16908198
TI  - Classification of functional brain images with a spatio-temporal dissimilarity
      map.
AB  - Classification of subjects into predefined groups, such as patient vs. control,
      based on their functional MRI data is a potentially useful procedure for clinical
      diagnostic purposes. This paper presents an automated method for classifying
      subjects into groups based on their functional MRI data. The proposed methodology
      provides general framework using preprocessed time series for the whole brain
      volume. Using a training set of two groups of subjects, the new methodology
      identifies spatio-temporal features that distinguish the groups and uses these
      features to categorize new subjects. We demonstrate the method using simulations
      and a clinical application that classifies individuals into schizotypy and
      control groups.

PMID- 16908199
TI  - Separating subjective emotion from the perception of emotion-inducing stimuli: an
      fMRI study.
AB  - fMRI was used to dissociate neural responses temporally associated with the
      subjective experience of emotion from those associated with the perception of
      emotion-inducing stimuli in order to better define the emotion-related functions
      of the amygdala, lateral orbital frontal cortex (OFC), and hippocampus. Subjects
      viewed aversive pictures followed by an extended post-stimulus period of
      sustained subjective emotion. Brain regions showing activation paralleling the
      period of sustained subjective emotion were distinguished from those showing
      activation limited to the period of aversive picture presentation. Behavioral
      results showed that subjective ratings of emotion remained elevated for 20 s
      after offset of the aversive pictures. fMRI results showed that viewing aversive
      pictures activated the amygdala, lateral OFC, and hippocampus. Subjective emotion
      (present both during and after aversive pictures) was temporally associated with
      activation in the right lateral OFC and left hippocampus but not the amygdala.
      Ratings of subjective emotion were correlated with activation in the right
      lateral OFC and left hippocampus. The results support direct amygdala involvement
      in emotion perception but suggest that amygdala activation is not temporally
      associated with subjective emotion that occurs after the offset of emotion
      related stimuli. The results are consistent with a general role for the lateral
      OFC in monitoring or reflecting on internal experience and show that hippocampal
      activation is sustained during a period of subjective emotion, possibly related
      to enhanced memory encoding for the aversive pictures.

PMID- 16908200
TI  - Classic identity negative priming involves accessing semantic representations in
      the left anterior temporal cortex.
AB  - Classic identity negative priming (NP) refers to the finding that when an object
      is ignored, subsequent naming responses to it are slower than when it has not
      been previously ignored (Tipper, S.P., 1985. The negative priming effect:
      inhibitory priming by ignored objects. Q. J. Exp. Psychol. 37A, 571-590). It is
      unclear whether this phenomenon arises due to the involvement of abstract
      semantic representations that the ignored object accesses automatically.
      Contemporary connectionist models propose a key role for the anterior temporal
      cortex in the representation of abstract semantic knowledge (e.g., McClelland,
      J.L., Rogers, T.T., 2003. The parallel distributed processing approach to
      semantic cognition. Nat. Rev. Neurosci. 4, 310-322), suggesting that this region
      should be involved during performance of the classic identity NP task if it
      involves semantic access. Using high-field (4 T) event-related functional
      magnetic resonance imaging, we observed increased BOLD responses in the left
      anterolateral temporal cortex including the temporal pole that was directly
      related to the magnitude of each individual's NP effect, supporting a semantic
      locus. Additional signal increases were observed in the supplementary eye fields
      (SEF) and left inferior parietal lobule (IPL).

PMID- 16908201
TI  - Immaturity of somatosensory cortical processing in human newborns.
AB  - The development of the early component of somatosensory evoked potentials (SEPs)
      from the neonatal N1 to adult N20 response has previously been described. The
      main emphasis has been on the change in the response latency during maturation.
      We used magnetoencephalography (MEG) to characterize the cortical generators of
      the N1 and the subsequent response in healthy human newborns. Furthermore, we
      studied the maturation of tactile processing according to responses evoked by
      tactile stimulation of the index finger in newborns, 6-month-old babies and
      adults. This study provides evidence of specific differences in the somatosensory
      processing in neonates compared to that in adults. Although the initial cortical
      response to electrical median nerve stimulation in the newborns was similar in
      field distribution to the corresponding N20m in adults, the subsequent major
      deflection in the response waveform had the opposite polarity. Similar immaturity
      in cortical processing was seen in the tactile evoked fields in both the newborns
      and the 6-month-old infants compared with the adults. Our results indicate that
      although the somatosensory pathway in full-term newborns is sufficiently
      developed to supply the brain with tactile information, the cortical neuronal
      networks for processing the input may not function in the same way as in adults.

PMID- 16908202
TI  - Further insights into the phylogeny of Arabidopsis (Brassicaceae) from nuclear
      Atmyb2 flanking sequence.
AB  - Arabidopsis thaliana is the preeminent plant model organism. However, significant
      advances in evolution and ecology are being made by expanding the scope of
      research beyond this single species into the broader genus Arabidopsis.
      Surprisingly, few studies have rigorously investigated phylogenetic relationships
      between the nine Arabidopsis species, and this study evaluates both these and
      hypotheses related to two instances of intra-generic hybridization. DNA sequences
      from the 5' flanking region of the nuclear Atmyb2 gene from 12 of the 14
      Arabidopsis taxa were used to reconstruct the generic phylogeny. The strict
      consensus tree was highly concordant with previous studies, identifying lineages
      corresponding to widespread species but exhibiting a large basal polytomy. Our
      data indicates that the paternal parent of the allopolyploid A. suecica is A.
      neglecta rather than A. arenosa s.l., although the need for a detailed
      phylogeographical study of these three species is noted. Finally, our data
      provided additional phylogenetic evidence of hybridization between Arabidopsis
      lyrata s.l. and A. halleri s.l. Taken together, the well-defined lineages within
      the genus and the potential for hybridization between them highlight Arabidopsis
      as a promising group for comparative and experimental studies of hybridization.

PMID- 16908203
TI  - Low-frequency electric cortical stimulation decreases interictal and ictal
      activity in human epilepsy.
AB  - We previously reported that low-frequency electric cortical stimulation (LFECS)
      directly applied to the epileptic focus by means of subdural electrodes decreased
      the number of interictal epileptiform discharges in patients with intractable
      partial epilepsy. In the present study, LFECS was applied to the epileptic foci
      directly in four patients with medically intractable partial epilepsy through
      subdural electrodes and evaluated its effect on the number of interictal
      epileptiform discharges as well as simple partial seizures. We used alternating
      electric current of 0.3 ms duration presented at 0.9 Hz frequency for 250 s.
      LFECS did not induce seizures in any of the four patients. In one patient, the
      number of interictal epileptiform discharge decreased significantly by LFECS,
      which is in conformity with our previous report. In addition, LFECS applied to
      the seizure onset zone decreased the frequency of simple partial seizures in one
      patient. These results suggest that LFECS has an inhibitory effect not only on
      the interictal but also the ictal activities in patients with intractable partial
      epilepsy. Further study is required to determine the inhibitory effect of LFECS
      more in details.

PMID- 16908204
TI  - DNA methylation in osteoarthritic chondrocytes: a new molecular target.
AB  - OBJECTIVE: To review the current knowledge of the mechanism of DNA methylation,
      its association with transcriptional silencing, possible mechanisms of hyper- and
      hypomethylation and how epigenetic changes may relate to the pathogenesis of
      osteoarthritis (OA). METHODS: Journal literature was searched using Pubmed. Since
      there are very few publications directly on epigenetic phenomena in OA, the
      search was extended to give an overview of epigenetic mechanisms as they relate
      to the molecular mechanisms of the disease. RESULTS: While the epigenetics of
      cancer cells have been intensively investigated, little attention has so far been
      paid as to whether epigenetic changes contribute to the pathology of non
      neoplastic diseases such as OA. This review explains the mechanisms of DNA
      methylation, its role in transcriptional regulation, and possible demethylation
      mechanisms that may be applicable to OA. Preliminary evidence suggests that
      changes in DNA methylation, together with cytokines, growth factors and changes
      in matrix composition, are likely to be important in determining the complex gene
      expression patterns that are observed in osteoarthritic chondrocytes. CONCLUSION:
      Early evidence points to a role of epigenetics in the pathogenesis of OA. Since
      epigenetic changes, although heritable at the cellular level, are potentially
      reversible, epigenetics could be a new molecular target for therapeutic
      intervention, especially early in the disease.

PMID- 16908205
TI  - Alteration of matrix glycosaminoglycans diminishes articular chondrocytes'
      response to a canonical Wnt signal.
AB  - OBJECTIVE: Although Wnt signaling is a key regulator of the chondrocyte life
      cycle during embryonic development, little is known about Wnt activity in
      articular cartilage. Recent studies have suggested an association between excess
      signaling through the canonical Wnt pathway and osteoarthritis (OA). Genetic and
      in vitro studies with Drosophila have shown that signaling by the orthologous
      protein, Wingless (Wg), is regulated by glycosaminoglycans (GAGs) found at the
      cell surface. The objective of this study was to determine whether alteration in
      GAG sulfation or matrix content, such as that occurs in OA cartilage, would
      affect articular chondrocytes' response to a canonical Wnt stimulus. METHODS:
      Cells were isolated from shoulder joints of young calves (bovine articular
      chondrocytes, bACs) and from human cartilage (human articular chondrocytes, hACs)
      discarded during total knee replacement for OA. Conditioned media from a cell
      line that is stably transfected with Wnt3a was used as a source of Wnt protein
      that activates the canonical signaling pathway. Conditioned media from the
      parental cell line was used as a control. beta-catenin levels were measured by
      immunoblot. In some experiments, chondrocyte cultures were treated with sodium
      chlorate (NaClO3) to inhibit GAG sulfation, or with chondroitinase ABC (ChABC) to
      digest chondroitin sulfate (CS) in the matrix. RESULTS: Cultured bACs showed low
      steady-state levels of beta-catenin that increased upon stimulation with Wnt3a. A
      decrease in either GAG sulfation or CS content diminished bACs' response to Wnt3a
      (approximately 40% and 37% of control, respectively). Similar effects on the
      response to Wnt3a via beta-catenin were observed for cultured hACs with
      undersulfation of GAGs (16% of control) and decreased CS content (20% of
      control). CONCLUSION: This study demonstrates that articular chondrocytes respond
      to canonical Wnt stimulation, and that reduced sulfation or CS content diminishes
      that response.

PMID- 16908207
TI  - Optical tweezer micromanipulation of filamentous fungi.
AB  - Optical tweezers have been little used in experimental studies on filamentous
      fungi. We have built a simple, compact, easy-to-use, safe and robust optical
      tweezer system that can be used with brightfield, phase contrast, differential
      interference contrast and fluorescence optics on a standard research grade light
      microscope. We have used this optical tweezer system in a range of cell biology
      applications to trap and micromanipulate whole fungal cells, organelles within
      cells, and beads. We have demonstrated how optical tweezers can be used to:
      unambiguously determine whether hyphae are actively homing towards each other;
      move the Spitzenkorper and change the pattern of hyphal morphogenesis; make
      piconewton force measurements; mechanically stimulate hyphal tips; and deliver
      chemicals to localized regions of hyphae. Significant novel experimental findings
      from our study were that germ tubes generated significantly smaller growth forces
      than leading hyphae, and that both hyphal types exhibited growth responses to
      mechanical stimulation with optically trapped polystyrene beads. Germinated
      spores that had been optically trapped for 25min exhibited no deleterious effects
      with regard to conidial anastomosis tube growth, homing or fusion.

PMID- 16908206
TI  - The achievement of durable complete cytogenetic remission in late chronic and
      accelerated phase patients with CML treated with Imatinib mesylate predicts for
      prolonged response at 6 years.
AB  - Despite the positive results achieved by Imatinib mesylate (Imatinib) in the
      treatment of chronic myeloid leukemia (CML), over the past several years,
      Imatinib does not eradicate the leukemic clone. The long-term duration of
      response to the drug is not known. Long-term follow-up of CML patients treated
      with Imatinib will ultimately define the durability of such treatment and the
      frequency of reemergence of progressive disease. We present the results of a 6
      year follow-up of 40 CML patients either in chronic or accelerated phase who
      obtained a durable (>6 months) complete cytogenetic remission (CCyR) after
      treatment with Imatinib in a single center. In 34 cases CCyR was obtained at an
      Imatinib dose of 400-600 mg/day and in 6 cases after a dose increase to 600-800
      mg/day. At a median follow-up of 68 months, 6 cytogenetic relapses (15%) were
      observed. No progressions to more advanced phases of disease have been detected
      during the follow-up period. Cytogenetic relapse was predicted by either a
      decrease in the amount of BCR-ABL transcript of less than 2 logs after the
      achievement of CCyR (p=0.0041) or a time-to-CCyR of more than 12 months
      (p<0.0001). This 6-year follow-up of the efficacy of Imatinib therapy in CML
      patients who obtained a durable CCyR indicates that the relapses rate is low over
      this period of observation and that the rate of relapse does not increase over
      time.

PMID- 16908208
TI  - An evaluation of the effect of clotting on the relationship between copper and
      caeruloplasmin in bovine blood.
AB  - The ratio of caeruloplasmin activity to copper concentration (CP:Cu) has been
      suggested as a more accurate determinant of the requirement for additional copper
      than plasma or liver copper concentrations. Although this test has no peer
      reviewed evidence of efficacy, it has been used by a large number of UK
      veterinarians. However, the available test uses a serum caeruloplasmin (sCP)
      activity to plasma copper (pCu) concentration ratio which, because of the
      preferential loss of caeruloplasmin during clotting, is likely to underestimate
      the true CP:Cu, although it has been suggested that the marginal range accounts
      for this. This study was undertaken to evaluate the effect of using serum copper
      (sCu) rather than pCu concentrations in calculating CP:Cu. Using sCu rather than
      pCu increased CP:Cu by more than was accounted for by the marginal range. Of 48
      cattle which were reported as 'low' using sCP:pCu, 22 were 'normal' when sCu was
      used instead of pCu. All herds with 'marginal' or 'low' mean CP:Cu when the
      sCP:pCu concentration ratio was used had 'normal' ratios when sCu was used
      instead of pCu.

PMID- 16908209
TI  - The correlation of the IGF-I, IGFBP-3, and ALS generation test to height velocity
      after 6 months of recombinant growth hormone therapy in girls with Turner
      syndrome.
AB  - BACKGROUND/AIMS: Girls with Turner syndrome (TS) have short stature and benefit
      from growth hormone therapy (hGH). Some TS present a significant change in height
      velocity in response to hGH while others have only a mild increment. Our
      objective was to correlate the response to hGH (height velocity after 6 months of
      therapy) to biochemical data prior to and after the beginning of hGH to try to
      define a tool to predict the response to hGH. METHODS: Thirteen TS participated
      in the study (ages 3.5-14 years). Levels of IGF-I and IGFBP-3 were measured
      before and 5, 30 and 90 days after starting hGH (0.05 mg/kg/day), ALS levels were
      measured only prior and after 5 days. RESULTS: The mean height velocity (+/-SD)
      increased from 4.27 (+/-1.18) cm/year to 8.46 (+/-2.17) cm/year (p=0.0001). There
      was no correlation between the height velocity encountered and the expected
      height velocity using published mathematical models. Basal ALS values correlated
      to height velocity SDS and IGF-I and IGFBP-3, after 90 days, correlated to height
      velocity. Most of the data was too scattered to be used individually for each
      patient. CONCLUSIONS: Even though we observed a relationship between biochemical
      markers and height velocity in TS treated with hGH, the response to hGH therapy
      in this condition is highly variable.

PMID- 16908210
TI  - Homology between ABH-carrier alpha2-seminoglycoprotein and Mac-2 binding protein.
AB  - alpha2-seminoglycoprotein (alpha2-SGP), purified from human seminal plasma, is a
      carrier of glycoprotein for the ABO blood grouping. The alpha2-SGP exists in the
      secretions of the seminal vesicle and various glands. However, the function of
      alpha2-SGP is, as yet, unknown. In this study, we determined that two internal
      amino acid sequences of 8 and 12 residues of alpha2-SGP were Ala-Val-Asp-Thr-Trp
      Ser-Trp-Gly and Thr-Leu-Gln-Ala-Leu-Glu-Phe-His-Thr-Val-Pro-Phe. These sequences
      were completely coincident with the domain 3 of human Mac-2 binding protein
      (M2BP), which was identified as a tumor-associated antigen. In addition, we also
      confirmed an alpha2-SGP binding activity to galectin-3 that was one of a ligand
      for M2BP, and the immunological cross-reactivity between alpha2-SGP and M2BP.
      These findings strongly suggested that alpha2-SGP was identical with M2BP.

PMID- 16908211
TI  - Establishment of an architecture-specific experimental validation approach for
      finite element modeling of bone by rapid prototyping and high resolution computed
      tomography.
AB  - A new experimental validation method for assessing the accuracy of large-scale
      finite element (FE) models of bone micro-structure at the apparent and tissue
      level was developed. Augmented scaled bone replicas were built using rapid
      prototype machines based on micro-computed tomography (micro-CT) data. The
      geometric accuracy of the model was evaluated by comparing experimental tests
      with the replicas to the FE solution based on the same micro-CT data. A new
      version of the large-scale FE solver was developed to incorporate orthotropic
      material properties, hence the experimentally determined properties of the rapid
      prototype material were input into the FE models. The modified FE solver
      predicted the experimental apparent level stiffness within less than 1%, and the
      difference between experimental strain gauge measurements and FE-calculated
      surface stresses was 7% and 49% on a flat and curved surface region,
      respectively. While absolute error estimates of surface stresses were limited due
      to strain gauge errors, the relatively larger difference on the curved surface is
      indicative of the limitations of a hexahedron FE model for representing such
      geometries. Although the validation approach is applied here for hexahedron based
      meshes, the method is flexible for varying bone architectures and will be
      important for validation of future large-scale FE modeling developments that
      utilize techniques such as mesh smoothing and tetrahedron elements.

PMID- 16908212
TI  - Assessment of muscle fatigue using sonomyography: muscle thickness change
      detected from ultrasound images.
AB  - Muscle fatigue is an exercise-induced reduction in maximal voluntary muscle
      force. As the surface electromyography (SEMG) can be used to estimate the
      features of neuromuscular activations associated with muscle contractions, it has
      been widely employed as an objective tool to evaluate muscle fatigue. On the
      other hand, ultrasound imaging can inherently provide the morphological
      information of individual muscle, thus the architectural changes of muscles
      during fatigue can be obtained. In this study, we demonstrated the feasibility of
      using the dimensional change of muscles detected by ultrasound images, named as
      sonomyography (SMG), to characterize the behavior of muscles when they were in
      fatigue. The SEMG signals of the muscles were also recorded simultaneously and
      used for comparison. The right biceps brachii muscles of 8 normal young male
      adult subjects were tested for 30s under 80% of the maximal voluntary isometric
      contraction. The muscle fatigue was indicated by the change of the root-mean
      square (RMS) and median frequency (MDF) of the SEMG signals. The results showed
      that the SEMG RMS had a linear increase with time with a rate of 2.9+/-1.9%/s
      (mean+/-S.D.), while the MDF decreased linearly with a rate of -0.60+/-0.26Hz/s.
      The muscle thickness, detected from the ultrasound images, continuously increased
      during the muscle fatigue but with a nonlinear increase with time, which was
      rapid during the initial 8.1+/-2.1s with a mean deformation rate of 0.30+/
      0.19%/s and then became slower with a rate of 0.067+/-0.024%/s up to 20s after
      the contraction. The muscle deformation at 20s was 3.5+/-1.6%. The results
      demonstrated that the architectural change of muscles detected using SMG could
      potentially provide complementary information for SEMG for the muscle fatigue
      assessment.

PMID- 16908213
TI  - Zonal differences in gallium-67 uptakes between perivenous versus periportal
      regions of rat liver following carbon tetrachloride treatment.
AB  - Gallium-67 ((67)Ga) has been used as a tumor or inflammation-imaging agent in
      nuclear medicine, although underlying mechanism has not been fully elucidated. To
      gain some insights into the mechanism of (67)Ga uptake by injured liver, we
      analyzed the difference between perivenous and periportal regions of rat liver in
      terms of (67)Ga uptake by hepatocytes at the site of inflammation caused by
      carbon tetrachloride (CCl(4))-treatment. Distribution of (67)Ga in rat liver
      sections was monitored with a BAS5000 system following hepatic injury by CCl(4)
      treatment. Periportal hepatocytes (PPH) and perivenous hepatocytes (PVH) were
      prepared by modified digitonin-collagenase perfusion technique. Uptakes of (67)Ga
      in PVH region and PPH region reached to a maximum 2 days after CCl(4)-treatment,
      and the amount of maximum uptake of (67)Ga in PVH was twice as much as that in
      PPH. Liver damage as measured by lipid peroxidation and (45)Ca uptake occurred in
      PVH region within 1 day after CCl(4)-treatment. Incorporation of
      bromodeoxyuridine into hepatocytes reached to a maximum 2 days after CCl(4)
      treatment, and peaked amount of DNA synthesis in PVH was twice as much as that in
      PPH. These results indicated that the uptake of (67)Ga by the PVH region was
      carried out during hepatic regeneration phase rather than hepatic damage period
      by CCl(4)-treatment.

PMID- 16908214
TI  - Nanocomposites based on poly-D,L-lactide and multiwall carbon nanotubes.
AB  - A possibility of poly-D,L-lactide modification by multiwall carbon nanotubes
      (MWCNT) has been shown. MWCNT were prepared from methane-air mixture upon
      atmospheric pressure without catalyst on high voltage atmospheric pressure
      discharge plasma set-up. According to scanning and transmission electronic
      microscope data carbon nanotubes diameters were within 12-60 nm. Quantities of
      MWCNT incorporated did not exceed 0.5%. Nanocomposites were obtained by
      sonification of mixture of a poly-D,L-lactide solution in chloroform and MWCNT
      followed by film casting on glass substrates. Tensile strength and
      thermomechanical properties of the dried composite films were investigated.
      Introduction of MWCNT into poly-D,L-lactide has been shown to cause the enhanced
      polymer stability to thermal oxidative destruction. Taking into account the
      results obtained one could anticipate that implants from nanocomposites of poly
      D,L-lactide with MWCNT would be dispersed in a living organism more slowly as
      compared to implants from pure poly-D,L-lactide without additives.

PMID- 16908215
TI  - Individual, social and home environment determinants of change in children's
      television viewing: the Switch-Play intervention.
AB  - Understanding potential determinants of change in television (TV) viewing among
      children may enhance the effectiveness of programs targeting this behaviour. This
      study aimed to investigate the contribution of individual, social and home
      environment factors among 10-year-old Australian children to change in TV viewing
      over a 21-month period. A total of 164 children (49% boys) completed a 19-lesson
      (9-month) intervention program to reduce TV viewing time. Children completed self
      administered surveys four times over 21 months (pre- and post-intervention, 6-
      and 12-month follow-up). Baseline factors associated with change in TV viewing
      during the intervention and follow-up periods were: 'asking parents > or
      =once/week to switch off the TV and play with them' (21.6 min/day more than those
      reporting <once/week, p=0.007); being able to 'watch just 1h of TV per day' (26.1
      min/day less than those who could not, p=0.010); 'watching TV no matter what was
      on' (36.6 min/day more than those who did not, p<0.001); and 'continuing to watch
      TV after their program was over' (33.0 min/day more than those who did not,
      p=0.006). With every unit increase in baseline frequency of TV viewing with
      family and friends, children spent on average 4.0 min/day more watching TV over
      the 21-month period (p=0.047). Baseline number and placement of TVs at home did
      not predict change in children's TV viewing over the 21 months. Greater
      understanding of the family dynamics and circumstances, as well as the individual
      and social determinants of TV viewing, will be required if we are to develop
      effective strategies for reducing TV viewing in children.

PMID- 16908217
TI  - Cardiovascular risk estimation by professionally active cardiovascular nurses:
      results from the Basel 2005 Nurses Cohort.
AB  - BACKGROUND: Nurses play a key role in the prevention of cardiovascular disease
      (CVD) and one would, therefore, expect them to have a heightened awareness of the
      need for systematic screening and their own CVD risk profile. The aim of this
      study was to examine personal awareness of CVD risk among a cohort of
      cardiovascular nurses attending a European conference. METHODS: Of the 340
      delegates attending the 5th annual Spring Meeting on Cardiovascular Nursing
      (Basel, Switzerland, 2005), 287 (83%) completed a self-report questionnaire to
      assess their own risk factors for CVD. Delegates were also asked to give an
      estimation of their absolute total risk of experiencing a fatal CVD event in the
      next 10 years. Level of agreement between self-reported CVD risk estimation and
      their actual risk according to the SCORE risk assessment system was compared by
      calculating weighted Kappa (kappa(w)). RESULTS: Overall, 109 responders (38%)
      self-reported having either pre-existing CVD (only 2%), one or more markedly
      raised CVD risk factors, a high total risk of fatal CVD (> or =5% in 10 years) or
      a strong family history of CVD. About half of this cohort (53%) did not know
      their own total cholesterol level. Less than half (45%) reported having a 10-year
      risk of fatal CVD of <1%, while 13% reported having a risk > or =5%. Based on the
      SCORE risk function, the estimated 10-year risk of a fatal CVD event was <1% for
      96% of responders: only 2% had a > or =5% risk of such an event. Overall, less
      than half (46%) of this cohort's self-reported CVD risk corresponded with that
      calculated using the SCORE risk function (kappa(w)=0.27). CONCLUSION: Most
      cardiovascular nurses attending a European conference in 2005 poorly understood
      their own CVD risk profile, and the agreement between their self-reported 10-year
      risk of a fatal CVD and their CVD risk using SCORE was only fair. Given the
      specialist nature of this conference, our findings clearly demonstrate a need to
      improve overall nursing awareness of the role and importance of systematic CVD
      risk assessment.

PMID- 16908218
TI  - Restrictive mitral inflow pattern is a strong independent predictor of lack of
      viable myocardium after a first acute myocardial infarction.
AB  - In patients with acute myocardial infarction (AMI) a restrictive mitral inflow
      pattern successfully predicts clinical outcome. The impact of myocardial
      viability on the mitral inflow velocities, however, is unknown. One hundred and
      forty-one patients with a first AMI underwent two-dimensional, Doppler and
      dobutamine stress echocardiography (DSE). Patients were classified into two
      groups based on Doppler measurement of left ventricular filling: a restrictive
      group (18 patients), and a non-restrictive group (123 patients). In the non
      restrictive group, myocardial viability at DSE was found in 56 patients, while in
      the restrictive group only three patients showed contractile reserve (46% vs.
      16%, p<0.03). The multivariate logistic regression analysis demonstrated that
      restrictive mitral inflow pattern was a strong independent predictor of lack of
      viable myocardium (OR=12.45, p<0.001).

PMID- 16908219
TI  - Treatment of patients with coexisting epileptic and nonepileptic seizures.
AB  - A majority of studies have reported a rate of concurrence of epileptic seizures
      (ESs) in patients with nonepileptic seizures (NESs) of about 10-18%. We explored
      the relationship between the two paroxysmal disorders (ESs and NESs) in a series
      of patients with both, and report a treatment for these patients that proved
      remarkably effective: reduction of the dose of antiepileptic drug to the minimum
      required to achieve optimal freedom from seizures. NESs are hypothesized to have
      a psychobiological basis, and it has been proposed that they be recognized as
      posttraumatic startle seizures. Excessive suppression of epileptic paroxysmal
      activity appears to favor the expression of posttraumatic paroxysmal activity in
      patients with both paroxysmal disorders, and the manifestation of ESs and NESs
      tends to alternate. Of etiological significance is the finding that the patients
      commonly have both a personal history of trauma and a family history of epilepsy.

PMID- 16908220
TI  - Metallothionein, antioxidant enzymes and DNA strand breaks as biomarkers of Cd
      exposure in a marine crab, Charybdis japonica.
AB  - Cadmium (Cd) is one of the most toxic heavy metals that are widespread in inshore
      sediments of China, and can induce the production of toxic hydroxyl radicals that
      cause cell damage. The present study investigated the effect of two Cd
      concentrations (the final Cd concentration of 0.025 and 0.05 mg/L, prepared with
      CdCl2 x 2.5H2O) on metallothioneins (MT), antioxidant enzyme activities
      (superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx))
      and DNA integrity (DNA strand breaks) for up to 15 days in the gills and
      hepatopancreas of the portunid crab Charybdis japonica. The result indicated that
      MT was significantly induced after 3 days, with a dose-response relation between
      MT contents and Cd concentrations in two tissues and has a time-response relation
      in hepatopancreas during the experimental period; SOD, CAT and GPx activities
      could be stimulated after 0.5 day, all attained peak value and then reduced
      during the experimental period, but were not inhibited at day 15, except SOD and
      CAT in gills. Gill was more sensitive to Cd than hepatopancreas, and the
      hepatopancreas was the main detoxification tissue to deal with oxyradicals. DNA
      strand breaks were induced after 0.5 day, and there was a positive dose-response
      relation between DNA damage levels and Cd concentrations in gills, rather than
      hepatopancreas due to higher DNA repair activities. These results suggest the
      mechanisms of Cd toxicity and detoxification strategies in both tissues of C.
      japonica; in addition, the use of the biomarkers as indices for biomonitoring
      potential toxic effect of Cd in situ is discussed.

PMID- 16908221
TI  - Transiently reorganized microtubules are essential for zippering during dorsal
      closure in Drosophila melanogaster.
AB  - There is emerging evidence that microtubules in nondividing cells can be employed
      to remodel the intracellular space. Here, we demonstrate an essential role for
      microtubules in dorsal closure, which occurs toward the end of Drosophila
      melanogaster embryogenesis. Dorsal closure is a morphogenetic process similar to
      wound healing, whereby a gap in the epithelium is closed through the coordinated
      action of different cell types. Surprisingly, this complex process requires
      microtubule function exclusively in epithelial cells and only for the last step,
      the zippering, which seals the gap. Preceding zippering, the epithelial
      microtubules reorganize to attain an unusual spatial distribution, which we
      describe with subcellular resolution in the intact, living organism. We provide a
      clearly defined example where cells of a developing organism transiently
      reorganize their microtubules to fulfill a specialized morphogenetic task.

PMID- 16908223
TI  - Rapid antibody screening by membrane chromatographic immunoassay technique.
AB  - This paper describes a novel membrane chromatographic immunoassay technique
      suitable for rapid screening of antibodies in serum samples. This technique could
      potentially be utilized for antibody screening in situations where screening for
      exposure to one of several possible antigens is required. A synthetic microporous
      membrane is first selectively loaded with antibodies from the test serum sample
      by hydrophobic interaction. The in situ affinity membrane thus formed is
      sequentially pulsed with the antigens corresponding to the antibodies being
      screened. From the antigen chromatogram peak profile thus obtained, inferences
      about the antibodies present in the serum sample can then easily be made. This
      technique in addition to being rapid and direct is conceptually simple, and does
      not use any expensive media or reagents. It would potentially be useful for rapid
      diagnosis of infections as well as for rapid assessment of conditions such as
      envenomation or exposure to toxic substances.

PMID- 16908222
TI  - Quantitative determination of uracil residues in Escherichia coli DNA:
      Contribution of ung, dug, and dut genes to uracil avoidance.
AB  - The steady-state levels of uracil residues in DNA extracted from strains of
      Escherichia coli were measured and the influence of defects in the genes for
      uracil-DNA glycosylase (ung), double-strand uracil-DNA glycosylase (dug), and
      dUTP pyrophosphatase (dut) on uracil accumulation was determined. A sensitive
      method, called the Ung-ARP assay, was developed that utilized E. coli Ung, T4pdg,
      and the Aldehyde Reactive Probe reagent to label abasic sites resulting from
      uracil excision with biotin. The limit of detection was one uracil residue per
      million DNA nucleotides (U/10(6)nt). Uracil levels in the genomic DNA of E. coli
      JM105 (ung+ dug+) were at the limit of detection, as were those of an isogenic
      dug mutant, regardless of growth phase. Inactivation of ung in JM105 resulted in
      31+/-2.6 U/10(6)nt during early log growth and 19+/-1.7 U/10(6)nt in saturated
      phase. An ung dug double mutant (CY11) accumulated 33+/-2.9 U/10(6)nt and 23+/
      1.8U/10(6)nt during early log and saturated phase growth, respectively. When
      cultures of CY11 were supplemented with 20 ng/ml of 5-fluoro-2'-deoxyuridine,
      uracil levels in early log phase growth DNA rose to 125+/-1.7 U/10(6)nt.
      Deoxyuridine supplementation reduced the amount of uracil in CY11 DNA, but
      uridine did not. Levels of uracil in DNA extracted from CJ236 (dut-1 ung-1) were
      determined to be 3000-8000 U/10(6)nt as measured by the Ung-ARP assay, two
      dimensional thin-layer chromatography of metabolically-labeled 32P DNA, and LC/MS
      of uracil and thymine deoxynucleosides. DNA sequencing revealed that the sole
      molecular defect in the CJ236 dUTP pyrophosphatase gene was a C-->T transition
      mutation that resulted in a Thr24Ile amino acid change.

PMID- 16908224
TI  - Simple, rapid and sensitive assay method for simultaneous quantification of
      urinary nicotine and cotinine using gas chromatography-mass spectrometry.
AB  - Nicotine is a major addictive compound in cigarette. Its smoke is rapidly and
      extensively metabolized to several metabolites in human. Cotinine as a major
      metabolite of nicotine is commonly used as a biomarker to determine active and
      passive smokers. Cotinine has a longer half-life ( approximately 20 h) compared
      to nicotine ( approximately 2h). A simple, sensitive, rapid and high throughput
      GC-MS method was developed for simultaneous quantification of urinary nicotine
      and cotinine in passive and active smokers. In the sample preparation method, the
      analytes and internal standard were first basified and followed by liquid-liquid
      extraction. Upon completion, anhydrous sodium sulphate was added to the solvent
      mixture to trap moistures. The clear extract obtained was directly injected into
      GC-MS, operating under selective ion monitoring (SIM) mode. Calibration curves in
      the range of 0.5-5000 ng/mL of the analytes in urine matrix were established with
      linear correlation coefficients (r(2)) greater than 0.997. The limit of detection
      for both nicotine and cotinine were 0.20 ng/mL. The mean recoveries for nicotine
      and cotinine were 93.0 and 100.4%, respectively. The within- and between-assay
      accuracies were between 2.1 and 7.9% for nicotine and between 0.7 and 11.1% for
      cotinine. Within- and between-assay precisions of 3.3-9.5% for nicotine and 3.4
      9.8% for cotinine were also achieved. The method can be used in routine
      assessment and monitoring of active smoking and exposure to environmental tobacco
      smoke. The applicability of the assay was demonstrated in a small-scale
      comparison study between smokers and non-smokers.

PMID- 16908225
TI  - Determination of metolazone in human blood by liquid chromatography with
      electrospray ionization tandem mass spectrometry.
AB  - A rapid, sensitive and accurate liquid chromatographic-tandem mass spectrometric
      method is described for the determination of metolazone in human blood.
      Metolazone was extracted from blood using ethyl acetate and separated on a C18
      column interfaced with a triple quadrupole tandem mass spectrometer. The mobile
      phase consisting of a mixture of acetonitrile, 10 mmol/l ammonium acetate and
      formic acid (60:40:0.1, v/v/v) was delivered at a flow rate of 0.5 ml/min.
      Electrospray ionization (ESI) source was operated in positive ion mode. Selected
      reaction monitoring (SRM) mode using the transitions of m/z 366-->m/z 259 and m/z
      321-->m/z 275 were used to quantify metolazone and the lorazepam (internal
      standard), respectively. The linearity was obtained over the concentration range
      of 0.5-500 ng/ml for metolazone and the lower limit of quantitation (LLOQ) was
      0.5 ng/ml. For each level of QC samples, inter- and intra-run precision was less
      than 8.07 and 3.56% (relative standard deviation (RSD)), respectively, and the
      bias was within +/-4.0%. This method was successfully applied to the
      pharmacokinetic study of metolazone formulation after oral administration to
      humans.

PMID- 16908226
TI  - Women's stories of birth: a suitable form of research evidence?
AB  - In the past one to two decades, midwifery care has taken a new direction, which
      encompasses a valuing of women's birth experiences. This move has been contingent
      upon, and congruent with the adoption of 'woman centred' care and a renewed
      emphasis on normal birth. In line with these developments, women's stories and
      anecdotes of birth and midwives stories of experience increasingly form the basis
      of presentations at midwifery conferences and forums. Overall, this philosophical
      realignment, which commenced in Australia in the early 1990s, has been applauded
      by many midwives in terms of a greater valuing of the wishes and experiences of
      childbearing women and as being consistent with a greater promotion of normal
      birth. Nonetheless, it also gives rise to several questions, regarding the
      suitability of this form of research evidence. In a bid to answer some of those
      questions, this paper aims to evaluate the use of stories and anecdotal evidence
      within midwifery. First, an overview is presented of the way in which stories of
      pregnancy and birth appear in the literature. Secondly, the value of stories as
      evidence is critiqued and, finally, the ratio of story based publications,
      compared to traditional research methodologies, is reviewed. This review aims to
      address an area poorly attended in the literature and asks specifically: Are
      women's birth stories a suitable form of research evidence in midwifery?

PMID- 16908228
TI  - Transmission and epidemiology of HIV/AIDS: a global view.
AB  - Since the first recognition of the condition that is now called AIDS, much has
      been learned. We now know that AIDS results from infection with HIV types 1 and
      2. Advancements in approaches to treatment, in the form of new types of
      medications, have changed the trajectory of illness by slowing progression and
      decreasing the incidence of HIV-associated opportunistic infections in the
      millions of people living with HIV infection, particularly in developed
      countries. In less developed areas of the world, HIV infection looks different,
      in part because of the differential availability of medications and health care.
      This article focuses on epidemiology of HIV infection and AIDS in the United
      States and worldwide, and on transmission, including susceptibility factors.

PMID- 16908229
TI  - Substance abuse, medications, HIV, and the community.
AB  - This article describes the experience of a medical internist caring for thousands
      of persons living with HIV/AIDS (PLWHA) for more than 23 years, many of whom have
      abused illicit substances and ethanol. Divided in three major sections, the
      article looks at the effects of substance abuse on HIV treatment and how a
      community physician rallies the health team, patients, and the community to
      address the issues that pose barriers to quality HIV care.

PMID- 16908230
TI  - Early intervention services for persons with HIV/AIDS and hepatitis C: a
      community health center perspective.
AB  - Visiting Nurse Association of Central Jersey has been involved in care for
      patients with HIV/AIDS since 1991. In that year, the organization received
      funding as the lead agency for a Title II grant to establish an HIV/AIDS
      Consortium consisting of over 20 organizations, including other home care
      agencies, hospitals, county boards of social service, and other community
      providers. The Consortium collaborated to establish a thorough network of
      services: housing, transportation, medical treatment, medication access, support,
      resource identification, and education for both the infected and affected. As the
      linkages became stronger, the quantity and quality of services increased so that
      patients were receiving state-of-the-art health care while wrapped in a blanket
      of comprehensive supportive services.

PMID- 16908231
TI  - Ancillary services for individuals living with HIV/AIDS.
AB  - Providing comprehensive care to those living with HIV/AIDS remains a daunting
      task. Access to early HIV medical care helps to delay an AIDS diagnosis, and
      ancillary services can help meet the non-medical needs of HIV-positive
      individuals, which can ultimately impact their ability to access medical care.
      Some research has been done measuring ancillary service provision and primary
      care entry and retention; however, due to the lack of a comprehensive system of
      care, it has been difficult to determine the true impact of ancillary service
      usage and health outcomes. Additional qualitative research examining ancillary
      service usage, health outcomes, and quality of life needs to be done to develop a
      standard model of appropriate and comprehensive HIV care.

PMID- 16908232
TI  - The experience of physical symptoms among women living with HIV.
AB  - As the number of women living with HIV and AIDS increases, so does survival time
      for individuals living with this chronic condition. Symptom existence, intensity,
      and bothersomeness greatly affect quality of life in women living with HIV and
      AIDS. Symptoms experienced by women living with HIV include symptoms related to
      HIV infection itself, those related to opportunistic infections, and those
      related to medications and treatments. Symptoms experienced by women include
      those common to both genders and those specific to females. The presence and
      intensity of symptoms varies with progression of the disease and with
      deteriorating status of HIV disease indicators. While research is limited on this
      topic, some research on the general symptom experience of women and on symptoms
      specific to or common among women has been done. Extended life expectancy among
      women with HIV increases the importance of nursing care focused on symptom
      assessment and symptom management. This article reviews research on symptoms
      commonly experienced by women living with HIV and presents implications for the
      care of women experiencing distressing symptoms.

PMID- 16908233
TI  - An HIV/AIDS education intervention for Nepalese adolescent females.
AB  - This study provides empirical evidence that an educational intervention improves
      knowledge, attitudes, and beliefs among Nepalese female adolescents. Health
      professionals need to better understand the cultural practices and the role of
      females in underdeveloped countries such as Nepal. It is also important to
      identify female risk status for diseases such as HIV/AIDS. There is also a need
      for implementing culturally appropriate educational interventions with larger
      samples in rural, as well as urban, areas of Nepal. Nurses can play an active
      role in empowering Nepalese females, and, along with the government, they can
      plan and implement efficacious HIV/AIDS prevention programs.

PMID- 16908234
TI  - Sex scripts and power: a framework to explain urban women's HIV sexual risk with
      male partners.
AB  - The risk of sexual transmission of HIV may be perceived to be real among young
      urban women; however, the risk of losing a male partner if one doesn't engage in
      unprotected sex may be perceived to be greater. Sex script theory, and Barrett's
      theory of power as knowing participation in change, are integrated into a
      framework to explain young adult urban women's sex scripted response of
      unprotected sex as a normative relationship-promoting behavior. It is proposed
      herein that by associating high-power sex scripts that involve health-promoting
      behaviors into the familiar sex scripts, new HIV risk-reducing behavior may be
      integrated into normative sex scripts because these are designed to fulfill
      familiar relationship needs.

PMID- 16908235
TI  - Depressive symptoms in HIV disease.
AB  - Although depressive symptoms are common in people living with HIV/AIDS, their
      reported prevalence varies greatly across HIV-positive populations, ranging from
      21% to 97%. Comparing these rates is complicated by the varied conceptualization
      of depression as a major depressive disorder (clinical depression) or depressive
      symptoms, and by the use of multiple methods of measurement. Knowledge of
      predictors of depressive symptoms can assist health care providers in the
      identification of those who are most at risk. Appropriate diagnosis, treatment,
      and referral are critical, because depressive symptoms have been associated with
      poorer disease outcomes. Additionally, self-management symptoms can be used to
      supplement more traditional treatment methods.

PMID- 16908236
TI  - The impact of nutrition on physiologic changes in persons who have HIV.
AB  - HIV affects almost all bodily systems, which can lead to recurrent opportunistic
      infections, weight loss, distribution of weight changes, and death. Malnutrition
      and wasting, two symptoms that interfere with nutrient availability,
      accessibility, and metabolism, are associated with higher morbidity and
      mortality. Nausea, vomiting, swallowing or chewing difficulties, or the response
      of the body to opportunistic infections or medications that are considered vital
      to the treatment of the disease may affect nutritional status. A positive
      nutritional balance may help to improve the immune and other body systems, and
      delay the progression of the disease, This article reviews the effect of the
      nutritional status on the physiologic changes in the person who is infected with
      HIV.

PMID- 16908237
TI  - HIV after age 55.
AB  - HIV/AIDS continues to increase among adults older than 50 years of age. Racial
      and ethnic minorities are still disproportionately affected by HIV/AIDS. The
      misconception that older adults are not at high risk for acquiring HIV/AIDS stems
      from a false impression that older adults are not sexually active and do not
      participate in risky behaviors that could result in HIV/AIDS. Studies show that
      older adult men and women engage in sexual intercourse--or some form of sexual
      behavior--at least weekly, and identify that risk factors for HIV/AIDS among
      adults older than 50 years of age include multiple sex partners, a high-risk
      partner, receipt of blood products between 1974 and 1984, or injection drug use.
      The development of new diagnostic resources, antimicrobial treatments, and
      antiretroviral therapy have made HIV/AIDS more chronic in nature, so that
      morbidity and mortality rates related to HIV/AIDS have declined. With this
      decline, HIV/AIDS has become a disease of chronicity rather than an acute
      illness.

PMID- 16908239
TI  - Closure and summary of Ninth International Small Bowel Transplantation Symposium.
AB  - The highlights of The Ninth International Small Bowel Transplantation Symposium
      included the latest results from the Intestinal Transplant Registry (ITR), which
      demonstrated that the number of transplants performed annually continued to rise
      to 180 per year, most of which were performed in the United States, where the
      greatest number of home parenteral nutrition (PN) patients live (a prevalence of
      around 40 per million or 10,000 individuals). The three largest programs in the
      United States all use anti-CD25 monoclonal antibodies, but three different forms
      of lymphocyte depletion are employed in induction protocols: (1) humanized
      monoclonal anti-thymocyte globulin; (2) pretreatment of the recipient with
      Campath; (3) pretreatment of the small bowel allograft with anti-lymphocyte
      globulin. The main gain in these new approaches has been in the reduction in
      tacrolimus and steroid exposure. Indeed, the Pittsburgh team reduced tacrolimus
      to alternate-day dosing and stopped steroids altogether at 6 months in some
      patients, recording 100% survival in the past 2 years. The ITR demonstration of a
      difference in survival between adult patients who are hospitalized (40% to 60%)
      versus those who are still at home (80% to 100% survival) when called to
      transplant makes it almost unethical to delay evaluating patients for small bowel
      transplantation once they start experiencing complications on home PN. The input
      of gastroenterologists is also crucial in making recommendations about isolated
      liver transplantation for individuals with a potential to come off PN. Several
      important papers with useful prognostic clinical data with respect to selecting
      patients for isolated liver transplant were presented. It is evident from
      demographic surveys that only 2% to 5% adult patients and 5% to 15% children in
      large, well-resourced PN programs will be unlucky enough to develop life
      threatening complications, but they must have rapid access to small bowel
      transplantation in this event. It is therefore important that the collaboration
      between gastroenterologists and the intestinal transplant teams continues. These
      excellent results for small bowel transplantation mean that the time is right for
      a large cost-effectiveness study comparing small bowel transplantation with PN.

PMID- 16908240
TI  - Total parenteral nutrition: challenges and practice in the cirrhotic patient.
AB  - Patients with cirrhosis develop metabolic derangements of protein, carbohydrate,
      and lipid metabolism. Malnutrition is commonplace and is associated with
      morbidity and mortality. Specific nutrient deficiencies may occur and enteral or
      parenteral nutritional support may improve outcome in appropriately selected
      patients. Parenteral nutrition itself has been associated with hepatic
      dysfunction, although the preponderance of evidence suggests that hepatic
      dysfunction is more a function of the underlying disorder and malabsorption.
      Intravenously infused organic nutrients may be metabolized differently than the
      same nutrient consumed enterally. The pathophysiology of total parenteral
      nutrition-associated liver disease is discussed as well as potential management
      options.

PMID- 16908241
TI  - Tolerogenic protocol for intestinal transplantation.
AB  - Transplantation is standard therapy for many patients suffering from kidney,
      liver, or heart failure. In contrast, transplantation of the intestine remains a
      high-risk procedure, which is performed in a minority of patients with short
      bowel syndrome. The difficulty is the strong alloimmune response caused by
      intestinal grafts and the complications of the profound immunosuppression. We
      tested a new clinical immunomodulatory protocol using donor-specific blood
      transfusion, a strategy that was popular before the introduction of cyclosporine
      and was recently shown to promote development of regulatory cells. Low-dose
      steroids and low-dose tacrolimus were administered based on previous observations
      that tolerance requires an intact immune system, that over-immunosuppression is
      counterproductive, and that high doses of calcineurin inhibitors block
      development of regulatory cells whereas low doses promote it. Finally,
      inflammation within the intestinal graft was minimized to reduce the additional
      stimulants that the innate immunity of the transplanted intestine exert on the
      adaptive immune response. Under this protocol, freedom from rejection was
      achieved in four consecutive intestinal transplant recipients using extremely low
      immunosuppression.

PMID- 16908242
TI  - Selection criteria and outcome of patients referred to intestinal
      transplantation: an European center experience.
AB  - Until 1998, intestinal transplantation (SBT) had not been performed in our region
      of Flanders, Belgium. Potential SBT activity was not known and selection criteria
      had not been validated. A multidisciplinary SBT program was launched in 1998. We
      analyzed requests for SBT and outcomes in these patients whether with or without
      SBT. Listing for SBT was only considered for patients with irreversible short
      bowel syndrome who had developed life-threatening complications of total
      parenteral nutrition, but whose general condition was still thought compatible
      with surgery and immunosuppression. During the study period 1998 to 2004, one
      third of the requests for SBT (10/31) were deemed suitable. SBT in this group was
      lifesaving (100% survival) when performed in time. Mortality in this group
      without SBT was high (67%). Two thirds of the patients (21/31) did not fulfill
      the SBT inclusion criteria, either because they were "too moribund" to tolerate
      transplantation or because they were "too well". This preliminary study
      emphasized the importance of (1) early referral of potential SBT candidates, (2)
      adherence to strict criteria for listing patients for SBT, and (3) referral of
      intestinal donors to procurement organizations.

PMID- 16908243
TI  - Quality of life on home parenteral nutrition or after intestinal transplantation.
AB  - AIM: We compared the health related quality of life (HRQOL) of stable patients on
      home parenteral nutrition (HPN) and of patients who underwent successful
      intestinal transplantation (ITx). METHODS: HRQOL was evaluated by the non-disease
      specific Short Form 36 instrument, which examines eight specific domains and
      scores them on a scale of 0% to 100%. Patient scores were standardized for the
      sex-matched and age-matched group scores of the healthy population by calculating
      the Z-score (reduced value: Z-score < -1). RESULTS: Eighteen patients on HPN and
      12 patients who underwent ITx were studied. The two groups did not differ for
      primary intestinal disease, cause of intestinal failure, presence of a stoma,
      body mass index, and employment and marital status. HPN Z-scores were physical
      functioning -2.3, physical role -1.5, body pain -1.0, general health -1.2,
      vitality -0.5, social functioning -0.9, emotional role -0.7, and mental health
      0.0. ITx Z-scores were physical functioning -1.7, physical role -0.8, body pain
      0.0, general health -0.4, vitality 0.0, social functioning -0.4, emotional role 
      0.3, and mental health 0.0. Only the body pain Z-scores differed significantly (P
      = .012). CONCLUSIONS: The value of the physical components of the SF-36 was
      reduced in all the components in the HPN patients and in the physical functioning
      component in the ITx patients. The mental health components were normal in both.
      Successful ITx showed a better subjective physical health feeling than stable
      HPN.

PMID- 16908244
TI  - Impact of positive preoperative surveillance blood cultures from chronic
      indwelling catheters in cadaveric intestinal transplant recipients.
AB  - Recurrent bloodstream infections are a common indication for intestinal
      transplantation (ITx). Often, clinical symptoms may be absent in the setting of
      bacteremia, especially in patients with chronic liver disease. This study
      investigated the incidence and impact of positive blood cultures (BCx) obtained
      from central venous catheters used for total parenteral nutrition (TPN) in
      asymptomatic patients immediately prior to cadaveric ITx. Of 13 consecutive
      patients transplanted between November 2003 and November 2004, 12 underwent
      preoperative surveillance BCx with four positives (33%). Isolates included
      Staphylococcus epidermidis (n = 2), methicillin-resistant Staphylococcus aureus,
      and Citrobacter freundii. All four patients with positive BCx displayed liver
      dysfunction at the time of transplant (> or = grade 2 fibrosis, total bilirubin
      >8.0 g/dL), three of whom were inpatients. In contrast, only three of eight
      nonbacteremic patients showed liver disease of comparable severity. Liver
      dysfunction and inpatient status at the time of transplant appear to predict
      positive blood cultures. Postoperative length of stay and time on the ventilator
      were significantly longer among bacteremic as compared with nonbacteremic
      patients, but there were no differences in intraoperative blood use, time to
      total parenteral nutrition independence, or operative time between bacteremic and
      nonbacteremic patients. Our study showed that occult bacteremia in asymptomatic
      pre-intestinal transplant patients was not uncommon and may increase
      postoperative morbidity. Preemptive removal of long-term central venous catheters
      should be considered prior to ITx.

PMID- 16908245
TI  - The Miami experience with almost 100 multivisceral transplants.
AB  - We report our experience with 98 patients who received primary multivisceral
      transplantations. Three eras can be distinguished based on the evolution of
      technique, immunosuppression, and monitoring: August 1994 to December 1997 (first
      era); January 1998 to December 2000 (second era); and January 2001 to present
      (third era). Sixteen patients were transplanted during the first era, 18 during
      the second era, and 64 during the third era. Fifty-three patients are alive with
      a median follow-up of 37.5 months (range: 1 to 116 months). The leading cause of
      mortality was infection (n = 17), followed by rejection (n = 6). Seven patients
      required retransplantation and five of them subsequently died. The estimated 3
      year survival was 25% +/- 11% for era 1; 44% +/- 12% for era 2; and 58% +/- 7%
      for era 3. Additionally, 45.3% (29/64) of patients in the third era never
      developed rejection versus 23.5% (8/34) of patients in the first two eras
      combined. The percentage of patients who developed a moderate or severe rejection
      was significantly less in the third era compared with the first two eras
      combined, 31.6% (20/64) versus 67.6% (23/34). A comparison of the hazard rate of
      developing severe rejection showed a protective effect of the multivisceral graft
      (P = .0001). In conclusion, multivisceral transplantation is indicated for
      patients with short bowel syndrome and extended abdominal catastrophies.
      Evolution in surgical techniques, immunosuppression, and monitoring have improved
      patient survival, which is now similar to that of other complex solid organ
      transplants.

PMID- 16908246
TI  - International grading scheme for acute rejection in small bowel transplantation:
      implementation and experience at the University of Miami.
AB  - In 2003, an international collection of pathologists and clinicians proposed a
      unified grading system for acute cellular rejection in endoscopically derived
      small intestine allograft biopsies. This grading system was implemented at the
      University of Miami over the past 2 years and the results are presented herein. A
      total of 1136 small bowel allograft biopsies with sufficient tissue for analysis
      were obtained from 123 hospitalized, clinic, and referral patients. The overall
      most common diagnosis assessing all time periods was grade IND (40%), and grade 1
      rejection or greater was present in 19% percent of biopsies. A suspected vascular
      component to the acute rejection as identified by specific mucosal vascular
      changes was present in 6% of cases. Clinical decision making was very consistent
      with different grades. Our experience has confirmed that this new grading system
      is reliable and identifies clinical subsets of patients that can receive
      different therapy. We recommend that this international grading system be
      implemented for acute cellular rejection in bowel allografts as a means to
      standardize pathological assessment of alloimmune-induced graft injury, which
      will allow comparisons between different centers and clinical trials.

PMID- 16908247
TI  - Mucosal fibrosis in intestinal transplant biopsies correlates positively with the
      development of chronic rejection.
AB  - Endoscopic biopsies of intestinal allografts are limited to the superficial
      layers of the bowel. We investigated whether the presence of mucosal fibrosis in
      graft biopsies was indicative of chronic allograft rejection. We examined graft
      biopsies of 182 intestinal transplant recipients for the presence of mucosal
      fibrosis. Kaplan-Meier analysis showed that within 5 years posttransplantation
      33% of intestinal transplant patients had graft biopsies positive for mucosal
      fibrosis. Although the presence of mucosal fibrosis did not affect patient or
      graft survival, patients with this lesion were at higher risk of developing
      chronic allograft enteropathy.

PMID- 16908248
TI  - Two cases of living-related intestinal transplantation.
AB  - We recently performed living-related small bowel transplant in two patients. The
      first patient was a 14-year-old boy with total parenteral nutrition (TPN)
      dependent short-bowel syndrome associated with hypoganglionosis. He received a
      bowel graft from his 43-year-old mother. The second patient was a 27-year-old
      female who had undergone massive enterectomy due to volvulus. She underwent
      living-related bowel transplantation from her 57-year-old mother. In both cases,
      blood types were ABO identical, cytotoxic cross matches were negative, and
      cytomegalovirus status was positive to positive in both cases. Up to one third of
      the donor bowel was harvested from the distal ileum. The graft vessels were
      connected to infrarenal aorta and inferior vena cava. The immunosuppressive
      regimen consisted of daclizumab, tacrolimus, and steroids. The first patient
      developed progressive acute cellular rejection on postoperative day 9, requiring
      OKT-3 therapy. Two months after transplantation, he was weaned off TPN,
      tolerating oral intake with a fully functioning graft. The second patient was
      weaned off TPN on day 29 with a functioning graft. Her metabolic disorder
      dramatically improved. This patient developed indeterminate acute cellular
      rejection on day 111, which was successfully treated with bolus injections of
      steroid. Both donors had no complications; they were discharged on day 10. Living
      related intestinal transplantation can be a treatment option for patients with
      short-bowel syndrome.

PMID- 16908249
TI  - Factors influencing outcome after intestinal transplantation in children.
AB  - We evaluated 131 patients (6 months-14 years) who experienced 21 deaths before
      listing, 11 continuing on the waiting list, 38 well on home parenteral nutrition,
      6 off parenteral nutrition and 59 transplanted (20 girls) aged 2.5 to 15 years,
      (18 >7 years). They received cadaveric isolated intestine (ITx, n = 31) or liver
      small bowel (LITx, n = 32), including right colon (n = 43; 23 LITx) for short
      bowel (n = 19), enteropathy (n = 20), Hirschsprung (n = 14), or pseudo
      obstruction (n = 6). Treatment included tacrolimus, steroids, azathioprine, or
      interleukin-2 blockers. After 6 months to 10.5 years, the patient and graft
      survivals were 75% and 54%. Sixteen patients (10 LITx) died within 3 months from
      surgery (n = 3), bacterial (n = 5) or fungal (n = 6) sepsis, or posttransplant
      lymphoproliferative disorder (n = 2). Rejection occurred in 27 patients,
      including 10 steroid-resistant episodes requiring antilymphoglobulins. The grafts
      were removed due to uncontrolled rejection in seven ITx recipients. Surgical
      complications were observed in 38 recipients (25 LSBTx) within 2 months,
      including bacterial (n = 22) or fungal (n = 11) sepsis, cytomegalovirus disease
      (n=12), adenovirus (n = 11), or posttransplant lymphoproliferative disorder (n =
      12). Forty-two children (19 LSBTx) are alive. Weaning from parenteral nutrition
      was achieved after 42 days (median). Factors related to death or graft loss were
      pre-Tx surgery (P < .01), pseudo-obstruction (P < .01), age over 7 years (P <
      .03), fungal sepsis (P < .03), steroid resistant rejection (P < .05),
      hospitalized versus home patient (P < .01), and retransplantation (P < .05).
      Colon transplant did not affect the outcome. Interleukin-2 blockers improved
      isolated ITx (P < .05). Early referral and close monitoring of intestinal failure
      and related disorders are mandatory to achieve successful ITx.

PMID- 16908250
TI  - Neuodevelopmental outcomes for children transplanted under the age of 3 years.
AB  - Our previous investigations on neurodevelopmental outcomes for intestinal
      transplanted infants revealed that while some children were able to achieve a
      normal developmental outcomes, most children suffered from significant motor
      delays and several experienced severe cognitive delays. In our current
      investigation, we were especially interested in children who are transplanted
      before the age of 3 years because the impact of the chronic illness and nutrition
      impairment on the infant's developing brain may be more severe than those
      children who receive a liver transplant. METHODS: We evaluated 34 infants using
      the Bayley Scales of Infant Development. Twenty-seven children received a
      liver/intestine or multivisceral transplant and seven received a liver
      transplant. RESULTS: Comparison of the two groups revealed that children
      receiving an intestine/multivisceral transplant have much poorer outcomes.
      Seventy-four percent of these children were significantly delayed mentally
      compared to only 57.14% of the liver transplant infants. Furthermore, 42.86% of
      the liver-transplanted infants were actually functioning in the normal range
      posttransplant. The intestinal/multivisceral transplant infants' motor
      development shows the most striking difference, with 96.3% being severely delayed
      as compared to liver transplant infants in whom only 71% experienced serious
      delays. The neurodevelopmental impact of organ failure and transplant before the
      age of 3 years may depending on the type of organ transplant. Our study found
      that it may be more likely to expect a good outcome for liver transplant patients
      than for intestinal and multivisceral transplanted infants. This difference maybe
      due to the overall severity of the disease and the possible impact of nutritional
      deficits early in infancy.

PMID- 16908251
TI  - Neurodevelopmental outcomes of infant multivisceral transplant recipients: a
      longitudinal study.
AB  - This longitudinal investigation compares cognitive and physical capabilities of
      transplant recipients, both before and after receiving an intestinal transplant.
      METHODS: Using the Bayley Scales of Infant Development, we conducted
      pretransplant and posttransplant assessments on nine children (4 males, 5
      females) who received either an isolated intestine, combined intestine and liver,
      or multivisceral transplants, with a mean age at transplant of 18 months (range 8
      29) and a mean time posttransplant of 2 months (range 1-4 months). RESULTS:
      Scores on the Mental Developmental Index reflected that a majority (55.6%) of
      patients who scored in the significantly delayed range prior to transplant
      remained in the significantly delayed classification after receiving a
      transplant. In addition, 33.3% showed a decrease in their mental classification;
      either from "mildly delayed" to "significantly delayed" or from "within normal
      limits" to "mildly delayed". Results on the Motor Developmental Index
      demonstrated that 78% of recipients had significant delays both before and after
      receiving a transplant, while 11.1% fell one standard deviation after
      transplantation. We found that the majority of children who experience
      developmental delays prior to transplant are still experiencing delays when they
      are discharged from inpatient care. In addition, those children receiving
      multivisceral transplantations, as opposed to an isolated bowel, may be at a much
      greater risk of developing and retaining both cognitive and physical delays.
      Early neurodevelopmental evaluations of these patients is essential for early
      parental education and compliance with early intervention services to maximize
      potential recovery and ability to obtain normal development.

PMID- 16908252
TI  - Results of intestinal and multivisceral transplantation in adult patients:
      Italian experience.
AB  - PURPOSE: We report our experience with intestinal and multivisceral
      transplantation in Italy. METHODS: We performed 23 adult isolated intestinal
      transplants and seven multivisceral ones, three with liver, between December 2000
      and June 2005. Indications for transplantation were loss of venous access (n =
      14), recurrent sepsis (n = 10), and electrolyte-fluid imbalance (n = 6), 14 of
      whom also presented with total parenteral nutrition (TPN)-related liver
      dysfunction. Immunosuppression was based on induction agents like daclizumab
      (followed by tacrolimus and steroids) in the first period; alemtuzumab or
      thymoglobulin (with tacrolimus) in a second period after 2002. RESULTS: The mean
      follow-up was 742 +/- 550 days. Three-year patient actuarial survival rate was
      88% for intestinal transplants and 42% for multivisceral (P = .015). Three-year
      graft actuarial survival rate was 73% for intestinal patients and 42.8% for
      multivisceral (P = .1). Graft loss was mainly due to rejection (57%).
      Complications were mainly represented by bacterial infections (92% of patients),
      relaparotomies (82%), and rejections (72%). Full bowel function without any
      parenteral nutrition or intravenous fluid support was achieved in 60% of
      recipients with functioning bowel including 95% on a regular diet. One patient
      underwent abdominal wall transplantation as well. DISCUSSION AND CONCLUSION:
      Intestinal transplantation has achieved high rates of patient and graft survival
      with even longer follow-up. Early referral of patients, especially in cases of
      TPN-liver disease, is mandatory to obtain good outcomes and avoid high mortality
      rates on the transplant waiting list. Immunosuppressive management remains the
      key factor to increase the success rate.

PMID- 16908253
TI  - Isolated liver transplantation for decompensated end-stage liver disease in
      children with intestinal failure.
AB  - Cholestasis progressing to end-stage liver disease (ESLD) is common in intestinal
      failure (IF) in infants. Isolated liver transplantation (OLT) is performed when
      eventual enteral sufficiency is expected. We reviewed our experience with OLT for
      ESLD in patients with residual IF. From 1998 to 2004, four IF patients underwent
      OLT for ESLD at our institution. Three were performed as UNOS status I for acute
      decompensation of chronic liver failure; one other with severe cholestasis with a
      living donor. The living donor recipient died within months after OLT of chronic
      respiratory failure despite normal liver function. One recipient remains on
      parenteral nutrition (PN) and continues to receive partial enteral feeds with
      normal liver function. Two other recipients became enterally sufficient after the
      OLT. Biliary complications occurred in two patients, one with late hepatic artery
      thrombosis. Resolution was achieved with serial balloon dilatations and the other
      by conversion from duct-to-duct anastomosis to a choledochoduodenostomy. The
      morbidity of OLT for this indication is higher than for others likely because of
      comorbidities like sepsis and pulmonary insufficiency. OLT is complicated further
      by the attempt to maximally preserve residual bowel length for the biliary
      reconstruction. OLT can be an emergent life-saving procedure in IF patients
      despite higher morbidity. Improved liver function and diminished portal pressures
      may shorten the time to enteral sufficiency. Management of parenteral nutrition
      after OLT can avoid ESLD and eliminate small bowel transplantation in selected
      patients.

PMID- 16908254
TI  - Growth after intestinal transplant in children.
AB  - Intestinal transplantation has been more frequent in children with intestinal
      failure. However, the growth after intestinal transplantation has not been well
      documented. The demographics, transplant information, postoperative
      complications, heights, and weights were obtained retrospectively from medical
      records on 23 children who underwent intestinal transplantation. Z-scores were
      calculated from the STAT Growth-BP, based on Centers for Disease Control and
      Prevention growth chart (2000). Transplantations were performed between 1999 and
      2004. Patient median age was 1.1 years (range 0.5 to 6.9 years). Twelve were boys
      and 11 girls. Seventeen children received multivisceral transplantations, one
      modified multivisceral transplantation, and five isolated intestinal
      transplantations. Baseline immunosuppression consisted of tacrolimus and
      corticosteroids. Daclizumab was used as induction agent in 18 patients;
      alemtuzumab, in five patients. Median pretransplant Z-scores were median -1.67 (n
      = 23) in weight, and median -3.36 (n = 21) in height. Pretransplant growth was
      significantly retarded. We analyzed significantly retarded patients with Z-score
      <-2.0. The change of weight Z-score from pretransplant was: 1.25 at 6 months (n =
      11), 1.46 at 12 months (n = 10), and 2.21 at 24 months (n = 7). The change of
      height Z-score: 1.9 at 6 months (n = 16), 1.42 at 12 months (n = 13), and 1.51 at
      24 months (n = 10). Z-score significantly improved (P < .002, ANOVA). Among the
      analyzed factors sex, age at transplant, length of stay, and rejection within 6
      months, were not associated with catch-up growth. Children with retarded growth
      showed significant catch-up after successful intestinal transplantation.

PMID- 16908255
TI  - Expanded use of multivisceral transplantation for small children with concurrent
      liver and intestinal failure.
AB  - Fifty-five children with liver and intestinal failure have been transplanted at
      our center under daclizumab induction therapy since 1998. Of those, 19 received
      five multiviceral transplantation (MVT), 12 liver-intestine-pancreas transplants,
      and 2 noncomposite liver and intestine transplants (NCLIT) before 2001 (group 1).
      During this period, MVT was only used in children with gastric dysmotility. After
      2001, we expanded the use of MVT. Therefore, 36 children in this period (group 2)
      received MVT except for two who received NCLIT. Median age was 1.08 in group 1
      and 1.06 in group 2. Median recipient weight was 8.2 kg in group 1 and 7.5 kg in
      group 2. Six-month, 1-, and 2-year patient survivals were 54%, 37%, and 32% in
      group 1 and 94%, 91%, and 71% in group 2 (P = .00037). A statistically
      significant difference was observed in freedom from rejection between the two
      groups with group 2 being favorable (P = .0019). A statistically significant
      difference was observed in freedom from rejection between the two groups with
      group 2 being favorable (P = .0019) Four died of rejection in group 1 (21%); none
      died of rejection in group 2. There have been two esophago-gastrostomy strictures
      (one in each group) and a serious reflux of this anastomosis (group 2).
      Strictures were treated with balloon dilatation, and the reflux was surgically
      corrected. In 24 recent cases, gastro-gastric anastomosis was used in MVT with no
      complications to date. No pancreatic rejection was seen. Small children tolerated
      MVT with improved survival rates and reduced rates of rejection. Use of MVT may
      be considered as an alternative to liver-intestine-pancreas transplant.

PMID- 16908256
TI  - Inclusion of spleen in pediatric multivisceral transplantation.
AB  - Inclusion of the donor spleen may be beneficial for small children who receive
      multivisceral transplantation (MVT) because asplenia is associated with increased
      risk of bacterial sepsis. Beginning in 2003, the spleen was transplanted together
      with multivisceral transplantation in 17 children under daclizumab induction
      (spleen group). The results were compared to 23 children who received
      multivisceral transplantation without the spleen (control group) with the same
      immunosuppression regimen. Median age of 17 patients who received a spleen was
      0.80 years (range 0.54-1.66). Platelet counts at 30 and 60 days posttransplant
      were significantly lower in the spleen group (average values: day 30: 399,000 vs
      636,000, P = .015; day 60: 413,000 vs 622,000, P = .0056). WBC counts at 30 and
      60 days posttransplant were also decreased in the spleen group but the difference
      was not statistically significant. Median rejection-free survival was 205 days in
      the spleen group and 101 days in the control group (P = NS). Median length of
      hospital stay was 39 days in the spleen group and 61 days in the control group.
      With a median follow-up of 398 days (spleen group) and 1232 days (control group),
      3 of 17 (17%) in the spleen group developed graft versus host disease (GVHD),
      whereas 1 of 23 (4.5%) in control group did (P = NS). In one patient in each
      group, GVHD was fatal. No patient developed posttransplant lymphoproliferative
      disorder (PTLD) in the spleen group, whereas 4 of 23 (17%) in the control group
      developed PTLD. One-year patient survival was 84% in the spleen group and 86% in
      the control group. Recipients of the spleen as part of a multivisceral graft had
      significantly lower platelet counts. Rejection-free survival may be prolonged,
      but the risk of GVHD may be increased.

PMID- 16908257
TI  - Analysis of rejection episodes in over 100 pediatric intestinal transplant
      recipients.
AB  - Rejection after intestinal transplant is a significant source of morbidity and
      mortality. We analyzed number of rejections, severity, and duration of episodes
      in pediatric recipients of intestinal transplants. One hundred eighteen
      intestinal transplants were performed: intestine (n = 27), liver-intestine (n =
      27), modified multivisceral (n = 7), and multivisceral (n = 57). A total of 186
      rejections were classified: mild (n = 89), moderate (n = 70), severe (n = 27).
      Duration of episodes doubled for each increasing step in severity. Treatment of
      mild rejection was with steroids, moderate rejection was treated with OKT3,
      severe rejection required OKT3 and organ removal. Most rejections occurred during
      the first month posttransplant, with the incidence of all rejections declining
      after 6 months posttransplant. Intestine and liver-intestine recipients had
      significantly higher probability of developing severe rejections, as compared to
      MVT. In summary, recipients of MVT seemed to be protected from rejection as
      compared to intestine or liver-intestine recipients.

PMID- 16908258
TI  - Isolated liver transplantation in an infant with ultrashort gut.
AB  - Intestinal function in children with very short bowel syndrome and related
      intestinal failure may improve after isolated liver transplantation. An infant
      with an ultrashort gut, ileo-cecal valve, and whole colon received total
      parenteral nutrition from the first days of life. Enteral feeding failed because
      of the progressive dilatation of the jejunal portion and motility disorders. He
      developed early severe cholestatic liver disease (aspartate transferase 186,
      alanine transferase 103 U/L, serum bilirubin 8.4 mg/dL) and subsequent liver
      failure. At 8 months of age, he benefited from isolated liver transplantation
      (left segment graft from living donor). His early posttransplant evolution was
      characterized by recovery of oral alimentation, improvement of digestive and
      absorption functions, but he did not achieve TPN-independence. At 20 months, 50%
      to 60% of his energy needs were covered by parenteral nutrition and he has
      satisfactory growth indices (3rd percentile for weight and height), reduced stool
      volume, and frequency. Isolated liver transplantation allowed, in this particular
      case, time for further intestinal adaptation thereby avoiding the need for
      intestinal transplantation early in life.

PMID- 16908259
TI  - Pediatric intestinal transplantation at Packard Children's Hospital/Stanford
      University Medical Center: report of a four-year experience.
AB  - We report a 4-year experience of a new program in pediatric intestinal
      transplantation. Among 50 children referred for evaluation, 27 were listed for
      transplantation. Two children originally listed for combined liver/small bowel
      transplant were changed to isolated intestinal transplant as rehabilitation
      efforts resulted in full recovery of hepatic function. Eighteen children received
      18 grafts: 12 liver/intestine, 5 isolated intestine, and 1 multivisceral. Mean
      age at transplant was 3.6 year with 75% of patients aged 0 to 2 years. Five
      listed children died while waiting and four were still on the list. Immunotherapy
      included antithymocyte globulin induction and tacrolimus, sirolimus, and
      prednisone maintenance. At 1 year, patient and graft survivals were 75% and 67%,
      respectively. For isolated intestine, 1 year survivals were 100% and 75%, while
      for combined liver/intestine, they were 71% for both. Enteral autonomy is 100%
      with total parenteral nutrition stopping by 35.8 days (mean). We had two patients
      develop posttransplant lymphoproliferative disorder and three, exfoliative
      rejection, one of whom recovered completely. In conclusion, our program in
      pediatric intestinal transplantation has become well established with a high
      proportion of smaller/younger children receiving grafts. Outcomes achieved levels
      expected based on The Intestinal Transplant Registry and UNOS criteria, which
      were better than expected for isolated intestinal transplants and achievement of
      enteral autonomy.

PMID- 16908260
TI  - Nutritional outcomes following pediatric intestinal transplantation.
AB  - BACKGROUND: This study sought to describe the long-term nutritional outcomes of
      children after intestinal transplant (SBT). METHODS: Between 1991 and March 2005,
      30 children received 33 SBT at a single center. Eligibility criteria included
      patient and graft survival >6 months. Weight, height, albumin, prealbumin, zinc
      (Zn), and essential fatty acid (EFA) levels were reviewed retrospectively.
      RESULTS: The 19 patients who met inclusion criteria had a median age at SBT of
      2.9 years. The majority of patients were male, Latino, transplanted for
      necrotizing enterocolitis and received combined liver-SBT. All patients were
      weaned off total parenteral nutrition to elemental formula at a mean of 39 days
      post-SBT. Seventeen of 19 patients were Zn deficient and four patients were EFA
      deficient post-SBT. CONCLUSIONS: Pre-SBT most subjects were significantly
      deficient in anthropometric and biochemical parameters. Post-SBT the mean Z score
      for weight and height improved significantly at year 1, then leveled off in year
      2. Serum protein levels improved from pre-SBT, yet remained low-normal. Zn
      deficiency was seen frequently after SBT and is under investigation. Children who
      developed EFA deficiency were on the same formula, receiving inadequate EFA
      supplementation. Successful SBT was associated with growth and maintenance of
      serum nutritional parameters but not with significant catch-up growth.

PMID- 16908261
TI  - Laser-Doppler flowmetry in the monitoring of the human intestinal allograft: a
      preliminary report.
AB  - During acute rejection, graft endothelium becomes a prime target for recipient
      immune cells. Animal studies have shown reduced microvascular perfusion, probably
      due to increased endothelial-leukocyte interaction and endothelial impairment,
      leading to graft damage. Using laser-Doppler flowmetry (LDF), we correlated the
      microvascular blood flow in the intestinal mucosa of five patients receiving
      multivisceral grafts with clinical events and pathology results. Measurements (n
      = 75) were performed during the first 4 weeks posttransplantation by inserting
      the LDF flexible probe through the ileostomy for 25 to 30 cm. Forty-six of the 75
      measurements were performed within 24 hours of endoscopy and biopsy. In
      uncomplicated cases, we recorded a gradual increase in mucosal perfusion during
      the first week posttransplantation that presumably reflected regeneration after
      reperfusion injury. Increased mucosal perfusion did not seem to correlate with
      rejection or other adverse clinical events. Sudden and sustained decreases in
      mucosal perfusion by 30% or more compared to the previous measurements were
      associated with septic episodes, rejection, or both. LDF revealed a good
      sensitivity in monitoring the intestinal microcirculation. It was able to
      indicate perfusion changes associated with acute rejection. The relatively low
      specificity of LDF may be compensated by the low invasivity, allowing frequent
      investigation. LDF may be an additional tool for routine monitoring of intestinal
      allografts.

PMID- 16908262
TI  - Two years' experience of acute rejection monitoring of intestinal transplant
      recipients by real-time PCR assessment of granzyme B and perforin up-regulation:
      considerations on diagnostic accuracy.
AB  - Granzyme B (GrB) and perforin are promising immunological markers to predict
      acute rejection of transplanted organs. Based on 2 years of experience with
      molecular monitoring on peripheral blood samples, we investigated the diagnostic
      accuracy of GrB/perforin gene up-regulation using real-time polymerase chain
      reaction (PCR) for prediction of acute cellular rejection (ACR) in intestinal
      transplantation recipients. Histology used as the reference standard. According
      to our definition of disease positivity (anything other than ACR score 0),
      GrB/perforin up-regulation showed 84% specificity but only 49% sensitivity.
      However, among the 26 false-negatives, 12 (46%) had an ACR score 1, which is
      indeterminate for rejection and no associated clinical manifestations; a further
      10 (39%) had a score of 2 following rejection therapy (a confounder for
      GrB/perforin analysis). Thus only 4 (15%) false-negatives were actually
      associated with the onset of robust acute rejection. These data suggest that real
      time PCR analysis for GrB/perforin up-regulation might play a role along with
      clinical criteria for detection of presymptomatic acute rejection episodes in
      intestinal recipients who require immediate endoscopy and pathological
      examination, especially during long-term follow-up.

PMID- 16908263
TI  - Incidence, clinical significance, and outcome of vascular alterations in
      intestinal biopsies after isolated small bowel transplantation: a single-center
      experience.
AB  - BACKGROUND: Mild and moderate vascular alterations in intestinal biopsies after
      isolated small bowel transplantation (SBT) have uncertain clinical significance.
      METHODS: We retrospectively investigated the incidence, association with acute
      cellular rejection (ACR), treatment, and outcome of mild and moderate vascular
      changes in 15 adult SBTs performed between December 2000 and October 2003. The
      semiquantitative Ruiz score for vascular changes in intestinal mucosa was used.
      RESULTS: A total of 332 biopsies were analyzed. All patients had at least one
      sample showing mild or moderate vascular injury, which was globally found in 117
      biopsies (35% of the total; 29% mild and 6% moderate). No cases of severe
      vascular injury were observed. First appearance of vascular alterations occurred
      2 to 36 days after SBT (median: 6). Patients with vascular injury had a higher
      incidence of associated ACR than patients without this feature (16% vs 5%, P =
      .001). Patients with moderate vascular injury were also more likely to have
      moderate-to-severe ACR than patients showing no or mild vascular changes (14% vs
      2%; P = .015). Treatment of rejection was more frequently administered with
      simultaneous diagnosis of ACR than in cases of isolated vascular alterations (84%
      vs 26%; P < .0001). Only one graft (7%) was lost due to severe ACR. DISCUSSION:
      Mild and moderate vascular changes are common findings in early post-SBT
      biopsies. They are frequently associated with ACR and parallel its severity. The
      clinical impact of mild or moderate vascular injury appears to be of little
      relevance.

PMID- 16908264
TI  - An association of lower serum citrulline levels within 30 days of acute rejection
      in patients following small intestine transplantation.
AB  - INTRODUCTION: In a prospective protocol we studied whether serum citrulline level
      within 30 days of an acute rejection was predictive of the episode. METHODS: An
      acute rejection episode was defined as the date of occurrence of any biopsy
      proven rejection in which treatment was initiated until two successive biopsies
      showed no further rejection. We compared the mean citrulline level based on
      values determined within 30 days of the start of an acute rejection episode with
      the mean citrulline level measured on the same patient during a rejection-free
      period. Serum citrulline measurements were available immediately prior to the
      occurrence of rejection for 22 patients who experienced 37 episodes. RESULTS: For
      the 12 episodes of mild rejection, the mean serum citrulline level +/- SE
      (standard error) was 15.0 + 2.3 micromol/L prior to rejection and 18.8 +/- 2.4
      micromol/L during the rejection-free periods. A paired t test of the mean
      differences was not significant (P = 17). For the 25 episodes of moderate or
      severe rejection, the mean serum citrulline level was 12.4 +/- 1.1 micromol/L
      before rejection and 18.8 +/- 2.0 micromol/L during the rejection-free periods. A
      paired t test of the mean difference was statistically significant (P = .002).
      CONCLUSIONS: Although further study of citrulline as a marker for the early
      detection of acute rejection episodes is needed, our hope is that its use will
      help to prevent some of these early episodes from evolving into full-blown
      moderate or severe grades of rejection.

PMID- 16908265
TI  - Is serum gentamicin level a good predictor of graft injury in intestinal
      transplantation?
AB  - INTRODUCTION: Following intestinal transplant (SBT), the early diagnosis and
      treatment of rejection is a major management aim. The diagnosis of rejection is
      based on histology of stomal biopsies. Oral gentamycin (2.5 mg/kg) was used for
      selective decontamination of the digestive system. Our hypothesis was that
      gentamycin might be absorbed in the presence of graft dysfunction. AIM: Our goal
      was to assess the correlation between serum gentamycin level and the health of
      the intestinal graft. SUBJECTS AND METHODS: Among 33 SBT performed from 1993 to
      2005, serum gentamycin levels were performed once weekly or more often when there
      was a suspicion of rejection. All data were analyzed retrospectively. RESULTS:
      Adequate trough levels were achieved for only 23 patients, six of whom had
      histologically proven rejection and only one did not have a raised gentamycin
      content. Five patients with raised levels but no rejection included two with
      severe intestinal ischemia and three with bowel obstruction/ileus. Four of the
      five patients required laparotomies. CONCLUSION: We concluded that in our study
      raised serum gentamycin levels were a good predictor of rejection or significant
      injury to the graft.

PMID- 16908266
TI  - Association of emergence of HLA antibody and acute rejection in intestinal
      transplant recipients: a possible evidence of acute humoral sensitization.
AB  - Development of HLA antibody has been associated with chronic allograft failure in
      kidney recipients. We tested HLA antibody in posttransplant sera of intestinal
      recipients: 126 sera from 28 pediatric recipients were tested for HLA antibody by
      flow PRA (f-PRA). Median age was 1.1 years (0.44-17). Graft types included
      isolated intestine (n = 6), liver and intestine (n = 3), modified multivisceral
      (n = 3), and multivisceral grafts (n = 16). Greater than 10% of either class I
      (CI) or class II (CII) f-PRA was considered positive, and >30% strongly positive.
      Five of 28 patients had positive f-PRA in multiple samples; the remaining 23 had
      either no positive or only one positive sample. Three patients had strongly
      positive f-PRA. Patients with multiple positive samples were recipients of two
      modified multivisceral and three multivisceral grafts. Only one of these patients
      had a positive PRA pretransplant. Cytotoxic cross-match at transplant was
      negative for all. The three with strongly positive f-PRA showed significant
      episodes of rejection around the time of positive samples. One of them who
      persistently had f-PRA value >80% (from day 13-113) died of refractory rejection.
      The other two had f-PRA of 76% and 53% during the early postoperative course with
      associated episodes of rejection. F-PRA value decreased with rejection therapy.
      Only one of the 23 patients (4%) with negative f-PRA had an episode of rejection
      around the time of sample collection. Development of HLA antibody after
      intestinal transplantation seems to have significant association with acute
      rejection episodes.

PMID- 16908267
TI  - Magnification endoscopy as a reliable tool for the early diagnosis of rejection
      in living related small bowel transplants: a case report.
AB  - The purpose was to determine whether magnification endoscopy (ME) accurately
      diagnosed rejection in living related small bowel transplants (LRSBTx) during
      initial morphological adaptation of segmental intestinal grafts. The small bowel
      recipient was a 44-year-old woman with short gut syndrome following multiple
      bowel surgeries for familial adenomatous polyposis. ME was enhanced by
      chromoendoscopy staining. Bowel mucosa was washed with acetic acid and stained
      with methylene blue for optimal visualization of mucosal villi and to improve the
      diagnostic yield of biopsies. The recipient underwent surveillance ME with biopsy
      16 times through the ileostomy in the first 9 months following transplantation.
      The recipient developed diarrhea in the postoperative course, which led to the
      suspicion of rejection. ME findings of patchy villus blunting were consistent
      with biopsy samples that showed mild acute cellular rejection. Episodes of
      rejection were treated with high-dose immunosuppressants and steroids. Reversal
      of rejection was monitored by follow-up ME, which showed increased length of
      villi and normalization of morphology. Biopsy confirmed these findings. The first
      endoscopy, at 5 days posttransplant, showed no evidence of intestinal ischemia.
      LRSBTx involves early morphological adaptation of the recipient small bowel
      mucosa, characterized by an increased length of villi. ME is a reliable technique
      to follow adaptation and detect early rejection. The superior imaging of small
      bowel mucosa created by ME chromoendoscopy enables early diagnosis and delivery
      of more prompt antirejection therapy to prevent progression of rejection. ME also
      confirmed that segmental LRSBTx caused minimal ischemic injury to the recipient.

PMID- 16908268
TI  - Intragraft gene expression profile during acute cellular rejection in clinical
      small bowel transplantation: a case report.
AB  - BACKGROUND: Acute cellular rejection (ACR) is a common complication of small
      bowel transplantation (SBTx) and the major cause of graft loss. However, little
      is known regarding the genetic graft response to ACR in clinical transplants. In
      this study, we have determined a genetic expression profile of intestinal graft
      response to ACR after living related (LR) SBTx. RESULTS: By identifying the
      expression profiles of reported markers of rejection we were able to identify 57
      genes that had significantly increased (more than twofold) expression in response
      to ACR. Known markers of rejection identified: MMP-9, MMP-2, VIP, IFNgamma, IL
      2R, MADCAM-1, HSP-60, and HSP-70 all had greater than twofold increased
      expression after ACR diagnosed (week 3 to week 6). The newly identified genes
      were: IFI27, EPST11, APAF1, LAP3, STK6, and MDK. CONCLUSION: Newly identified up
      regulated genes in response to ACR in small bowel graft are involved in the
      immune response, cell adhesion, neurogenesis, cell division and proliferation,
      DNA replication/repair, protein ubiquitin/proteolysis, and apoptosis. TNFalpha up
      regulated early at week 2 biopsy may be an early genetic marker of ACR in SBTx.

PMID- 16908269
TI  - Gene expression profiles characterize early graft response in living donor small
      bowel transplantation: a case report.
AB  - BACKGROUND: The cellular and histological events that occur during the
      regeneration process in invertebrates have been studied in the field of visceral
      regeneration. We would like to explore the molecular aspects of the regeneration
      process in the small intestine. The aim of this study was to characterize the
      gene expression profiles of the intestinal graft to identify which genes may have
      a role in regeneration of graft tissue posttransplant. METHODS: In a patient
      undergoing living related small bowel transplantation (LRSBTx) in our
      institution, mucosal biopsies were obtained from the recipient intestine and
      donor graft at the time of transplant and at weeks 1, 2, 3, and 6 posttransplant.
      Total RNA was isolated from sample biopsies followed by gene expression profiles
      determined from the replicate samples (n = 3) for each biopsy using the
      Affymetrix U133 Plus 2.0 Human GeneChip set. RESULTS: Two profiles were obtained
      from the data. One profile showed rapid increase of 45 genes immediately after
      transplant by week 1 with significant changes (P < .05) greater than threefold
      including the chemokine CXC9 and glutathione-related stress factors, GPX2 and
      GSTA4. The second profile identified 133 genes that were significantly decreased
      by threefold or greater immediately after transplant week 1, including UCC1, the
      human homolog of the Ependymin gene. CONCLUSION: We have identified two gene
      expression profiles representing early graft responses to small bowel
      transplantation. These profiles will serve to identify and study those genes
      whose products may play a role in accelerating tissue regeneration following
      segmental LRSBTx.

PMID- 16908270
TI  - Intestinal transplantation with alemtuzumab (Campath-1H) induction for adult
      patients.
AB  - BACKGROUND: Alemtuzumab (Campath-1H [C1H]) is a humanized monoclonal antibody
      directed against the CD 52 antigen that is present on the surface of T cells, B
      cells, natural killer cells and monocytes. We studied its application in
      intestinal transplantation. METHODS: This is a retrospective review of adult
      patients who underwent intestinal transplantation between December 1994 and May
      2005. Group 1: non-C1H group (n = 39); group 2: C1H group (n = 37). C1H was
      administered as an induction immunosuppression in four doses (0.3 mg/kg), or in
      two doses (30 mg/kg). Tacrolimus levels were maintained at low level (5-10
      ng/dL). No maintenance steroids were given. RESULTS: One-year survival of group 1
      and group 2 patients were 57% and 70%, respectively. This difference is not
      statistically significant. Of 37 patients in group 2, 21 are alive. The incidence
      of rejection was lower in group 2 (P < .005). Average current tacrolimus level is
      6.97 +/- 3.98 ng/dL. Seventeen patients (81%) are steroid free, and 15 (71%) are
      maintained solely on tacrolimus. There was no graft versus host disease in group
      2. CONCLUSIONS: Our preliminary data suggest that C1H can provide effective
      immunosuppression for intestinal transplantation. Incidence of rejection was less
      with this regimen using low maintenance tacrolimus and minimal steroids.

PMID- 16908271
TI  - CD55 and CD59 deficiency in transplant patient populations: possible association
      with paroxysmal nocturnal hemoglobinuria-like symptoms in Campath-treated
      patients.
AB  - Campath-1H therapy is directed to CD52, a small mw protein that has a
      glycosylphosphatidylinositol (GPI) anchor, which has a conventional structure
      similar to other GPI anchors such as CD55 and CD59. Paroxysmal nocturnal
      hemoglobinuria (PNH) results when cells have a somatic defect in the synthesis of
      GPI anchors and lack CD55 and CD59, as well as CD52. Several patients treated
      with Campath developed PNH-like symptoms with hemolysis and thrombosis. These
      patients were followed after therapy by measurement of peripheral CD55 and CD59
      levels and showed an increased number of cells deficient in the expression of
      these molecules. Thereafter we instituted a screening program for the presence of
      CD55/59 levels in all pretransplant patients. Our results show that 17.3% of all
      pretransplant samples contained abnormal (9.7% of samples) or slightly abnormal
      (7.6% of samples) levels of granulocytes deficient in CD55 or CD59. This high
      prevalence of CD55/59 deficiency in Campath-treated patients with PNH-like
      symptoms suggests that a lack of these molecules (including CD52) could
      predispose to a complication of this immunosuppressive therapy.

PMID- 16908272
TI  - Analysis of risk factors for the development of posttransplant
      lymphoprolipherative disorder among 119 children who received primary intestinal
      transplants at a single center.
AB  - Posttransplant lymphoproliferative disorder (PTLD) is a well-known complication
      after pediatric transplantation. We analyzed all potential risk factors to assess
      patient and graft outcomes of 119 children who received intestinal
      transplantations. MATERIALS AND METHODS: Between August 1994 and March 2005, 119
      patients underwent cadaveric intestinal transplantation. Their median age at
      transplant was 1.4 years (range: 0.6-17), median weight was 9.5 kg (range: 4.7
      67), and 57% were boys. The median follow-up among 49 ongoing survivors was 41
      months (range: 4-121). All PTLD cases were biopsy proven. In the past 5 years,
      treatment included antiviral therapy, immunosuppression withdrawal, and use of
      rituximab. RESULTS: The incidence of PTLD was 11.8% (14/119). No patient
      experienced graft failure secondary to PTLD, while two patients died from PTLD
      (14.2%). The PTLD group was divided into an early onset group (<4 months, 6 of
      14; 42.8%) and a late onset group (>2 years, 8 of 14; 57.2%). No patient
      experienced PTLD between 4 months and 2 years after transplantation. The use of
      OKT3 was the only significant risk factor for the development of PTLD. No factor
      was specifically associated with the early versus late development of PTLD.
      CONCLUSIONS: The only factor associated with a significantly higher risk of PTLD
      was the use of OKT3 to treat a rejection episode. Finally, since the the
      introduction of anti-CD20 antibodies as part of the treatment protocol for PTLD,
      the risk of death due to PTLD appears to have become manageably low.

PMID- 16908273
TI  - Renal function after pediatric intestinal transplant.
AB  - Data were analyzed from 44 patients who survived more than 2 years after
      intestinal transplantation performed between 1994 and 2002. Median age was 1.7
      years. Tacrolimus level was defined as average tacrolimus level over 6 months.
      Kidney function was evaluated using a 6-month average serum creatinine.
      Glomerular filtration rate (GFR) was calculated with the Schwartz formula. The
      procedures were: isolated intestinal transplantation (n = 11), liver and
      intestinal transplantation (n = 9), multivisceral transplantation (n = 22), and
      modified multivisceral transplantation (n = 2). Forty-four patients were followed
      for a mean of 3.6 years on tacrolimus. Tacrolimus levels ranged between 3.5 and
      19.9 ng/mL (median 14.6 ng/mL) at 0 to 6 months and 6.0 to 18.9 ng/mL (median
      13.2 ng/mL) at 0 to 12 months. Pretransplant kidney function as mean GFR was 138
      +/- 42 mL/min/1.73 m(2) (n = 44), posttransplant kidney function at 18 to 24
      month as mean GFR was 102+/-35 mL/min/1.73 m(2) (n = 44), a value that was 81% of
      the pretransplant GFR (P < .0001). In an analysis of tacrolimus level versus
      renal function, a value greater than 13.5 ng/mL during the first 12 months was a
      significant predictor for impaired renal function at 2 years after
      transplantation (defined as average GFR less than 90 mL/min/1.73 m(2) at 18 to 24
      months; P = .001). Only age among age, sex, diagnosis, transplant type, and
      rejection episodes showed a correlation with renal function. Renal function
      dropped significantly at 2 years after pediatric intestinal transplantation to
      81% of the pretransplantation value. Tacrolimus level for the first 12 months
      seemed to predict subsequent development of renal impairment at 2 years.

PMID- 16908274
TI  - Renal dysfunction following adult intestinal transplant under tacrolimus-based
      immunosuppression.
AB  - We analyzed data from the records of 24 adult patients who survived more than 2
      years after intestinal transplantation performed between 1995 and 2002 under
      tacrolimus-based immunosuppression. Ages ranged from 19.3 to 59.2 years old
      (median 32.1 years). Tacrolimus cumulative level was defined as a sum of weekly
      average tacrolimus level over time. Kidney function was evaluated by the 6-month
      average serum creatinine level. Estimated creatinine clearance was calculated
      with the Cockcroft-Gault formula. Student's t test was used for analysis. Primary
      diseases were mesenteric thrombosis (n = 7), trauma (n = 4), Crohn's (n = 3),
      Gardner's (n = 5), and others (n = 7). Procedures were isolated intestinal
      transplant (n = 10), liver and intestine (n = 1), multivisceral transplant (n =
      9), or modified multivisceral transplant (n = 4). Cumulative tacrolimus levels
      ranged between 1161 and 8623 ng*day/mL (median 4132 ng*day/mL) at 0 to 12 months.
      Pretransplant kidney function as mean creatinine clearance was 114 mL/min per
      1.73 m(2) (n = 24). Creatinine clearance decreased to a mean of 49.6 mL/min per
      1.73 m(2) (43.5% of pretransplant) at 2 years (P < .0001). The average creatinine
      clearance at 18 to 24 months in each patient with a cumulative tacrolimus level
      <4500 ng*day/mL was 63% +/- 25% of preoperative creatinine clearance. In patients
      with a cumulative tacrolimus level >4500 ng*day/mL, it was 34% +/- 17%.
      Cumulative tacrolimus level >4500 ng ng*day/mL was significantly associated with
      a decreased creatinine clearance at 2 years (P = .006). Renal function decreased
      significantly after intestinal transplantation in adults. Cumulative tacrolimus
      level in the first year affected renal function at 2 years.

PMID- 16908275
TI  - Temporary elevation of serum transaminases after pediatric intestinal
      transplantation: incidence and clinical correlation in multivisceral transplant
      vs isolated intestinal transplant.
AB  - Data were gathered from the records of 51 children of median age 1.5 years who
      survived more than 6 months after intestinal transplantation. Abnormal liver
      function tests (LFTs) were defined as serum aspartate aminotransferase (AST)
      greater than 100 IU/L or total bilirubin greater than 2.0 g/dL lasting more than
      3 days. Temporary elevation was defined when LFTs returned to normal without
      graft loss or death. LFT elevation at the time of transplantation was not
      included as a temporary LFT elevation. Median follow-up was 36 months. In
      multivisceral transplant recipients, all patients (n = 34) showed abnormal LFTs
      at transplantation that normalized within a median period of 2 days. Temporary
      LFT elevations were seen in 20 of 34 (59%) in multivisceral transplantation and 5
      of 17 (29%) in isolated intestinal transplantation. Median length of elevation
      was 14 days in multivisceral transplantation and 12 days in isolated intestinal
      transplantation. Peak AST was 353 +/- 190 IU/dL in multivisceral transplantation
      and 839 +/- 605 IU/dL in isolated intestinal transplantation (P = .0059). Events
      associated with temporary LFT elevations in multivisceral transplantation were
      total parental nutrition (TPN) (n = 8), dehydration (n = 2), viral infection (n =
      2), others (n = 3), and nonspecific (n = 5). Events in isolated intestinal
      transplantation were posttransplant lymphoproliferative disorder (n = 2), TPN (n
      = 1), and nonspecific (n = 2). Temporary LFT elevations were commonly seen among
      pediatric intestinal recipients, which correlated with events other than
      rejection. Approximately half of the temporary LFT elevations were associated
      with no significant clinical events. They resolved spontaneously. Interestingly,
      the peak AST value was higher in isolated intestinal transplantation compared to
      multivisceral transplantation.

PMID- 16908276
TI  - Etiology and management of alimentary tract ulcers in pediatric intestinal
      transplantation patients.
AB  - Patients who undergo intestinal transplantation encounter several complications
      in the posttransplant period, one of them being ulcer formation in the alimentary
      tract. During postoperative endoscopic monitoring of 112 pediatric intestinal
      transplantation patients at our institution, we identified chronic ulcer
      formation in 11 patients. There were no common or defining demographic or
      clinical variables that were found in the patients with ulcers. The ulcers could
      be located within the allograft or in native tissue. Biopsies were obtained from
      the ulcer edge and the intervening mucosa as well as an evaluation of possible
      infectious agents. The most common changes in the ulcers were compatible with
      Epstein-Barr virus-associated posttransplant lymphoproliferative disorder (PTLD;
      seven cases), acute rejection (six cases), and less commonly, infectious causes
      (one case). These changes could occur concomitantly and retrospective analysis
      after therapy showed that the ulcers could have multiple etiologies. Directed
      biopsies of ulcer edges often displayed morphological changes compatible with
      acute rejection of the graft, although some biopsies of the intervening mucosa
      did not show similar changes. Some patients treated based on the changes within
      the intervening mucosa responded well and led to resolution of the ulcers. Our
      findings demonstrate that PTLD and acute rejection are the most common causes of
      chronic ulcer formation and that biopsy samples should be collected
      simultaneously from both the ulcer edge and intervening mucosa since pathological
      changes can vary depending on the underlying cause(s). Infectious agents were
      rarely present but could be seen superimposed with the underlying cause.

PMID- 16908277
TI  - Acellular dermal matrix provides a good option for abdominal wall closure
      following small bowel transplantation: a case report.
AB  - Following small bowel transplantation (SBTx), approximating the midline abdominal
      fascia can be problematic in patients with severely retracted abdominal cavities.
      We first report the use of acellular dermal matrix (ADM) for abdominal closure
      following living related SBTx. A 44-year-old woman with ultra-short gut syndrome
      secondary to multiple bowel resections received a 160-cm segmental intestinal
      graft from her daughter. The graft ileocolic vessels were anastomosed end to side
      to the inferior vena cava and distal aorta. A terminal ileostomy was fashioned
      because the patient had previous panproctocolectomy. The graft perfused well, and
      the laparotomy was primarily closed. On postoperative day 1, the patient required
      surgical exploration for evacuation of hematoma. Due to graft edema in a
      significantly retracted abdominal cavity, a 12x7 cm fascia defect was evident.
      Leaving the abdomen open or using a mesh was not entertained as options due to
      the high risk of infections. Primary closure under tension would also jeopardize
      the transplant, increasing the risk of thrombosis. The fascia defect was closed
      using a segment of ADM. The patient did well and went home on the postoperative
      day 11. At 2-year follow-up she is well and on oral diet without fascia defect or
      incisional hernia. This is the first report of the use of ADM for abdominal
      closure in patients receiving a SBTx. ADM is considered safe when used in
      contaminated sites and can allow primary closure of difficult wounds often seen
      in SBTx patients.

PMID- 16908278
TI  - Transplantation of preconditioned intestinal grafts is associated with lower
      inflammatory activation and remote organ injury in rats.
AB  - Reperfused grafts--particularly the intestine--release free radicals and
      cytokines into the systemic circulation. The type of discharge, which is greatly
      dependent on the local injury, may also induce inflammatory activation in distant
      organs and leading to multiple system and organ failure. It has been suggested
      that intestinal grafts from tacrolimus (TRL)-pretreated donors show improved
      morphology and microcirculation. We studied whether transplantation of intestines
      from TRL-pretreated donors influenced inflammatory response and remote organ
      injury posttransplantation. Donor Sprague Dawley rats received TRL or saline
      (controls) intravenously at 6 hours prior to graft harvest. The intestinal grafts
      were preserved in saline for 3 hours before transplantation. At 6 and 12 hours
      postreperfusion hepatic and renal cortical microcirculation were assessed using
      laser-Doppler flowmetry (n = 8-12 per group). Blood pressure was measured; liver,
      kidney, and serum samples were obtained. We analyzed hepatic and renal ICAM-1
      expression and caspase-3-like activity as well as plasma content of tumor
      necrosis factor-alpha and interleukin-6. Pretreated graft recipients had higher
      mean arterial pressure (82 +/- 10 vs 51 +/- 17 mm Hg, P < .05) and renal
      perfusion at 6 hours whereas liver perfusion was similar at both 6 and 12 hours.
      Liver and renal functions were also superior among recipients of pretreated
      grafts. Both caspase-3-like activity and ICAM-1 expression in liver and kidney
      were lower in pretreated graft recipients. Plasma IL-6 levels were lower in
      animals receiving pretreated grafts. Transplantation of intestines from TRL
      pretreated donors was followed by a lower systemic inflammatory response,
      improved organ function and decreased remote injury early posttransplantation
      compared with animals receiving grafts from untreated donors.

PMID- 16908279
TI  - Autonomic dysfunction of rat jejunum submitted to cold ischemic preservation is
      prevented by heparin.
AB  - Previous studies suggest that cold ischemic preservation (CIP) employed in small
      bowel transplantation promotes loss of intestinal motility due to severe lesions
      in autonomic enteric nerves. This autonomic dysfunction may be prevented by
      antioxidant agents. In this work, we investigated whether preservation with
      heparin prevented autonomic dysfunction of rat jejunum submitted to CIP for a
      long time. Jejunal segments (2 cm) of Wistar rats (12 to 16 weeks old) were
      preserved at 4 degrees C in Ringer's lactate solution without (-) or with (+) 100
      UI/mL heparin (H). After preservation for 12 hours, H+ and H- preparations were
      mounted in parallel in isolated organ baths containing 10 mL Tyrode's solution at
      37 degrees C for the study of neurogenic contractions evoked by electrical field
      stimulation (EFS; 10-30 Hz, 1-ms duration, 60 V) or by stimulation of nicotinic
      (NIC) or muscarinic (carbachol, CCh) cholinoceptors. The effects of NIC
      (hexamethonium, HEX) and muscarinic (atropine, ATR) antagonists were studied on
      these contractions. Contractions induced by EFS (30 Hz) were four times greater
      in H+ (1.02 +/- 0.12 g) versus H- (0.26 +/- 0.07 g), while contractions induced
      by NIC (1 mmol/L) were also four times higher in H+ (1.07 +/- 0.10 g) than H-
      (0.25 +/- 0.09 g) preparations. In addition, contractions induced by CCh (1
      mmol/L) were two times higher in H+ (1.21 +/- 0.13 g) than in H- (0.65 +/- 0.10
      g). EFS, NIC, and CCh contractions were inhibited by pretreatment of jejunum with
      HEX or ATR (1 mumol/L/30 min), in H+ and H-. These results indicated that
      addition of heparin to a preservation solution attenuated the autonomic
      dysfunction of rat jejunum submitted to CIP for a long time.

PMID- 16908280
TI  - Atenolol attenuates autonomic dysfunction of rat jejunum submitted to cold
      ischemic preservation.
AB  - In vitro studies have demonstrated that cold ischemic preservation (CIP) employed
      in small bowel transplantation produces loss of intestinal motility due to severe
      lesions of autonomic enteric nerves and that this autonomic dysfunction is
      attenuated by antioxidant agents. In this work, we investigated whether
      preservation with atenolol attenuated autonomic dysfunction of rat jejunum
      submitted to long-term CIP. Jejunal segments (2 cm) of Wistar rats (12 to 16
      weeks old) were surgically isolated and preserved at 4 degrees C in Ringer's
      lactate solution without (-) or with (+) 1 mumol/L atenolol (AT). After
      preservation for 12 hours, AT+ and AT- preparations were mounted in parallel in
      isolated organ baths containing 10 mL Tyrode's solution at 37 degrees C for the
      study of neurogenic contractions evoked by electrical field stimulation (EFS; 10
      to 30 Hz, 1-ms duration, 60 V) or by stimulation with nicotinic (nicotine, NIC)
      or muscarinic (carbachol, CCh) cholinoceptor agents as well as nicotine
      (hexamethonium, HEX) and muscarinic (atropine, ATR) antagonists. Contractions
      induced by EFS (30 Hz) were 46% higher in AT+ (0.38 +/- 0.02 g) than AT- (0.26 +/
      0.01 g), while contractions induced by NIC (1 mmol/L) were 84% higher in AT+
      (0.46 +/- 0.03 g) than in AT- (0.25 +/- 0.02 g). In addition, contractions
      induced by CCh (1 mmol/L) were 34% higher in AT+ (0.87 +/- 0.06 g) than in AT-
      (0.65 +/- 0.08 g). EFS-, NIC-, and CCh-induced contractions were inhibited by
      pretreatment of jejunum with HEX or ATR (1 mumol/30 min), in AT+ and AT-. These
      results suggest that addition of atenolol in the preservation solution attenuated
      autonomic dysfunction of rat jejunum submitted to long-term CIP.

PMID- 16908281
TI  - Intestinal preservation injury: a comparison between different rat strains.
AB  - AIMS: Comparison between the extensive information on intestinal preservation
      injury in the rat is challenging since various preservation solutions, technical
      details, and grading systems have been used. This study investigates if strain
      represents another relevant variable for preservation injury outcome. METHODS:
      Grafts from Piebald-Viral-Glaxo (PVG), Lewis, Brown Norway (BN), Wistar, and
      Sprague-Dawley (SD) male rats (n = 8/strain) were used. Grafts were perfused and
      stored at 4 degrees C in University of Wisconsin (UW) solution (with or without
      luminal preservation). Intestinal histology was evaluated at 8, 16, and 24 hours
      of preservation using the Park score. Lactate, lactate dehydrogenase (LDH),
      alkaline phosphatase (ALP), and glucose were measured in the preservation
      solution. RESULTS: Grafts from PVG and Lewis showed significantly lower injury
      scores compared to BN, Wistar, and SD at 8 and 16 hours, a difference that
      disappeared at 24 hours of preservation. Luminal preservation significantly
      reduced the injury score for all strains, except SD, at 8 and at 16 hours, a
      difference that disappeared at 24 hours. Biochemical analyses of LDH and lactate
      levels show a similar pattern both between different strains and the effect of
      luminal preservation, although not statistically significant. CONCLUSION:
      Different rat strains seem to have different susceptibility to intestinal
      preservation injury under identical conditions. These results indicate that PVG
      and Lewis are more resistant to preservation injury than Wistar, BN, or SD. The
      beneficial effect of luminal preservation with UW solution is limited after 8 to
      16 hours.

PMID- 16908282
TI  - Acute rejection in allogeneic rodent small bowel transplantation causes smooth
      muscle dysfunction via an inflammatory response within the intestinal muscularis.
AB  - INTRODUCTION: Isogeneic intestinal transplantation elicits an inflammatory
      response within the intestinal muscularis that is associated with dysmotility.
      Usually the inflammation and the postoperative motor dysfunction resolve within a
      few days after small bowel transplantation (SBTx). However, the onset of acute
      rejection in allogeneic SBTx is again associated with dysmotility. We
      hypothesized that dysmotility during acute rejection is based on coexpression of
      kinetically active mediators by the alloreactive leucocyte infiltrate. MATERIALS
      AND METHODS: Rat SBTx (BN to Lew and BN to BN) was performed without
      immunosuppression. Animals were sacrificed at 1, 4, and 7 days after SBTx.
      Leukocyte infiltration was investigated in muscularis whole mounts by
      immunohistochemistry. Mediator mRNA expression was determined by reverse
      transcriptase polymerase chain reaction. Muscle contractility was assessed in a
      standard organ bath. RESULTS: Transplanted animals showed a significant
      inflammatory response within the muscularis at day 1 after SBTx. However,
      allogeneic transplanted animals exhibited a significant second inflammatory peak
      at day 7 (mRNA induction: iNOS 150-fold; tumor necrosis factor-alpha 18-fold;
      interferon-gamma 397-fold), parallel to the onset of rejection. This change was
      associated with a significant leukocyte infiltration. Compared to controls,
      allogeneic transplanted animals showed a 29% decrease in smooth muscle
      contractility on days 1 and 4 and a 71% decrease of contractility on
      postoperative day 7. CONCLUSIONS: The motor dysfunction of transplanted small
      bowel during acute rejection is associated with an inflammatory reaction in the
      intestinal muscularis. The initial unspecific inflammation process immediately
      after transplantation is reactivated and intensified during acute rejection.

PMID- 16908283
TI  - Prevention of warm ischemic injury by neuropeptide bombesin in small bowel
      transplantation.
AB  - PURPOSE: This study investigated whether preoperative administration of
      neuropeptide bombesin (BBS) had a protective effect against IR/I and subsequent
      acute rejection. METHODS: Allogeneic SBTx was performed heterotopically in rats
      (n = 18). That were administered FK506 (0.32 kg/d) daily. The rats were divided
      into three groups of six rats each: group 1, BBS(-)5: warm ischemic time (WIT); 5
      minutes without BBS; group 2, BBS(-)15: WIT; 15 minutes without BBS; group 3,
      BBS(+)15: WIT; 15 minutes with BBS. The specimens were obtained from the stoma
      site at 1 hour after reperfusion and on postoperative days (PODs) 1 and 7. The
      graft mucosal state and degree of acute rejection were evaluated by H and E
      staining. The apoptotic cells in the crypt lesion were evaluated using TUNEL
      immunohistochemistry. An apoptotic index (AI) was calculated for quantitative
      analysis. RESULTS: H and E staining revealed that on POD 1 the mucosal villi were
      shortened in the BBS(-)15 group compared with the other two groups. One hour
      after reperfusion, the AI in BBS(-)15 group was 125.0 per thousand +/- 37.2 per
      thousand, which was significantly higher (P < .05) than that in the BBS(-)5 group
      (32.6 per thousand +/- 5.0 per thousand) or the BBS(+)15 group (32.0 per thousand
      +/- 3.0 per thousand). On POD 7, the AI in the BBS(-)15 group was 63.7 per
      thousand +/- 5.03 per thousand, which was significantly higher (P < .05) than in
      the BBS(-)5 (17.3 per thousand +/- 4.6 per thousand) or the BBS(+)15 group (12.3
      per thousand +/- 3.06 per thousand). CONCLUSIONS: Even a short WIT of 15 minutes
      induced considerable allograft mucosal damage, which also heightened the
      possibility of acute rejection. Exogenous BBS prevented mucosal damage by IR/I
      and was also beneficial to prevent acute rejection.

PMID- 16908284
TI  - Use of hyperbaric oxygenation in small bowel preservation for transplant.
AB  - INTRODUCTION: The aim of this work was to study the effects of hyperbaric
      oxygenation as a preservation technique for small bowel transplantation. METHODS:
      Twenty 2-month-old male Wistar rats weighting 250 g were divided into two groups:
      group A (n = 10) in which the small bowel was preserved for 12 hours, and group B
      (n = 10) in which the small bowel was preserved for 24 hours. After vascular and
      intraluminal perfusion, 3-cm segments were maintained in Ringer's solution at
      temperatures between 2 degrees C to 4 degrees C and in normobaric O2 conditions
      (groups A1, B1) or conditioned in an hyperbaric O2 metal chamber (100% oxygen at
      5.5 absolute atmospheres) (groups A2, B2). After this preservation time, we
      studied intestinal tissue injury and morphometric analysis of the villi. RESULTS:
      Mucosal injury was significantly greater among group A1 compared to group A2
      animals. The grade of the lesions was greater among group B1 compared to group B2
      animals. Group A1 showed no difference from Group B1. For lesion grade, the range
      was smaller in group A2 and group B2 animals. The villi height was significantly
      smaller in groups A1 and B1 compared to the other groups; whereas it was higher
      in group A2 as compared with B2. CONCLUSION: Hyperbaric oxygenation may play a
      role as a preservation technique. Further research is necessary.

PMID- 16908285
TI  - Threshold level of NF-kB activation in small bowel ischemic preconditioning
      procedure.
AB  - Ischemic preconditioning (IPC), which is obtained by exposure to brief periods of
      vascular occlusion, improves organ tolerance to prolonged ischemia. The aim of
      this study was to evaluate the threshold level of NF-kB activation in small
      intestine during an IPC procedure. Various intestinal IPC were performed on 20
      Wistar rats in seven groups: group I (GI, nonpreconditioned); group II (GII, 1
      minute ischemia and 1-minute reperfusion); group III (GIII, two cycles of 1
      minute ischemia and 1-minute reperfusion); group IV (GIV, 2-minutes ischemia and
      2-minutes reperfusion); group V (GV, two cycles of 2-minute ischemia and 2-minute
      reperfusion); group VI (GVI, 5-minute ischemia and 10-minute reperfusion); group
      VII (GVII, two cycles of 5-minute ischemia and 10-minute reperfusion). Bowel
      biopsies were collected after laparotomy (control) as well as at 30, 60, and 120
      minutes following IPC. We determined the cytoplasmic and nuclear NF-kB by a
      chemiluminescence-based ELISA method. Our results showed low, constant NF-kB
      levels in GI. In the preconditioned groups (GII-GVII), NF-kB was significantly
      elevated at 30 minutes following IPC (P < .05 vs control). After 1 hour, NF-kB
      activity decreased to the control level. However, 2 hours after IPC both forms of
      NF-kB were elevated significantly again, which was independent of the number of
      IPC cycles (P < .05 vs control). Our experiments revealed that one cycle of 1
      minute ischemia and 1-minute reperfusion is a critical threshold level for NF-kB
      activation during small bowel IPC. Longer and more IPC cycles did not result in
      further elevation of NF-kB activation.

PMID- 16908286
TI  - Effects of ulinastatin on postoperative systemic inflammatory response of
      recipients of rat small bowel transplantation.
AB  - AIM: We sought to evaluate the effects of ulinastatin on postoperative systemic
      inflammatory responses of recipients of rat small bowel transplantations (SBT).
      METHODS: Twenty-four recipients of rat heterotopic SBT were randomly divided into
      a control group and a treated group. Ulinastatin (50,000 U/kg(-1)/d(-1)) was
      injected intravenously 30 minutes before graft revascularization. Measured
      variables included plasma concentrations of tumor necrosis factor (TNF),
      interleukin (IL)-6, and C-reactive protein (CRP) on postoperative days 1 and 3.
      RESULTS: Administration of ulinastatin attenuated the postoperative increases in
      plasma concentrations of TNF, IL-6, and CRP. CONCLUSION: Ulinastatin attenuated
      the postoperative systemic inflammatory response of rat recipients of SBT.

PMID- 16908287
TI  - FK778 does not impair intestinal allograft absorption in a preclinical model of
      total small bowel transplantation.
AB  - Malononitrilamide 715 (FK778), a new low-molecular weight immunosuppressant,
      inhibits both T-cell and B-cell function by acting on the pathway for de novo
      pyrimidine biosynthesis. Pyrimidines are important for intestinal trophism; their
      inhibition may predispose to metabolic and functional impairments, such as
      diarrhea and malabsorption. In this study we assessed the absorptive capacity of
      intestinal allografts in a large-animal model of small bowel transplantation
      (SBTx) in pigs chronically treated with FK778. Ten outbred pigs underwent total
      orthotopic SBTx. Immunosuppression consisted of oral tacrolimus (trough levels 5
      15 ng/mL) and oral FK778 (4 mg/kg per day) administered for 60 days. The D-xylose
      absorption test was performed at day 60 to evaluate carbohydrate absorption.
      Results were compared to normal controls. Eight of the 10 animals were alive and
      in good condition at day 60. All of their allografts were free of rejection. The
      animals had a mean maximal weight loss of 6.4% during the study period; the final
      weight was comparable to the initial weight (P > .05). Diarrhea was present in
      all animals (mean 16% of postoperative days). The D-xylose curves showed that
      absorption in the transplanted animals at day 60 was similar to that in the
      untreated controls (P > .05). The absence of differences was confirmed by the
      statistical analysis. In conclusion, our preclinical study in pigs showed that
      chronic treatment with FK778 in combination with tacrolimus did not impair
      carbohydrate absorption by the allograft after SBTx.

PMID- 16908288
TI  - FK778 and tacrolimus combination therapy to control acute rejection after pig
      intestinal transplantation.
AB  - Malononitrilamide 715 (FK778) is a new class of low molecular weight
      immunosuppressant. Experimental studies in heart, liver, and kidney
      transplantation have shown a strong synergism when FK778 is used in combination
      with tacrolimus and when its administration is delayed by 7 days after the
      transplant. Following this indication, in a swine model of orthotopic small bowel
      transplantation (SBT), we assessed the efficacy of combined low dose tacrolimus
      and FK778 administered from day 0 or day 7. The entire small bowel was replaced
      in 16 piglets: group 1 (n = 5), no immunosuppression; group 2 (n = 6) oral
      tacrolimus to maintain whole blood trough levels between 5 and 15 ng/mL plus
      FK778 4 mg/kg per day; group 3 (n = 6) oral tacrolimus as in group 2 plus FK778 4
      mg/kg per day administered after a 7-day delay posttransplant. The median
      survival was 8 days in group 1, 60 days in group 2, and 13 days in group 3. The
      differences between group 2 and 1 and between group 2 and 3 are statistically
      significant. Three episodes of major bacterial infection were detected in both
      group 2 and 3 (0.5 episode/animal). The infectious-related mortality was 0% in
      group 2 and 50% in group 3 (P < .05). Acute cellular rejection was absent or mild
      in all group 2 and 3 stomal biopsies. In conclusion, combining tacrolimus and
      FK778 allowed prolonged survival after SBT in swine when FK778 was started at the
      time of SBT. The delayed administration of FK778 resulted in a high incidence of
      lethal infectious complications.

PMID- 16908289
TI  - Early outcome of different steroid-free regimens in small bowel transplantation:
      a large-animal study.
AB  - The intestine is a highly immunogenic organ that requires heavy immunosuppression
      (IS); therefore corticosteroid withdrawal after clinical small bowel
      transplantation (SBT) has not been standardized. In this study, we compared
      different immunosuppressive regimens (none with steroid or induction treatment)
      in a SBT pig model. Large White unrelated piglets were transplanted and divided
      into four groups as follow: group 1 (n = 3): no IS; group 2 (n = 10): IS with
      tacrolimus only; group 3 (n = 10): IS with tacrolimus and mycophenolate mofetil;
      group 4 (n = 5): IS with tacrolimus and rapamycin. Follow-up time was 30 days.
      All IS drugs were given orally; tacrolimus whole blood levels ranged between 5
      and 15 ng/mL in all groups except for group 2 whose tacrolimus whole blood levels
      ranged between 15 and 25 ng/mL. Group 1 pigs died of graft acute rejection (ACR)
      after a median of 12 days. Overall survival in groups 2, 3, and 4 at day 30 was
      40%, 80%, and 60%, respectively. Biochemical parameters, including glycemia and
      cholesterol, were into the normal range with no significant differences between
      groups. At the end of the study, one animal in group 2 and another one in group 4
      showed histological signs of moderate to severe ACR. The incidence of infection
      was higher in group 2 (2.1 episodes/pig) compared to group 3 (1.25) and group 4
      (1.6). This large-animal study demonstrates that tacrolimus-based IS without
      corticosteroids allows, in the early postoperative period (30 days) after SBT,
      good survival rates without an increased risk in the incidence of rejection.

PMID- 16908290
TI  - The role of dendritic cells in the gastrointestinal field effect.
AB  - INTRODUCTION: Intestinal manipulation leads to local bowel wall inflammation that
      subsequently spreads over the entire gastrointestinal tract. Previously, this
      gastrointestinal field effect had been demonstrated by us in a rodent model. We
      herein postulated an immunologic mechanism mediated by activated leukocytes. The
      aim of this study was to investigate the activation, maturation and migration of
      dendritic cells (DC) of the intestinal smooth muscle following surgical trauma
      and i.p. lipopolysaccharide challenge. METHODS: Mice underwent standardized
      intestinal manipulation or iP LPS administration and tissues (intestinal
      muscularis, Peyer's patches, mesenteric lymph nodes, and spleen) were obtained at
      various times after manipulation. DC were isolated by tissue digestion and
      separated by CD11c-iMAG. The harvested DC were analyzed by FACS. The activation
      pattern of DC was analyzed by polymerase chain reaction. RESULTS: We found a
      significant increase in DC within the intestinal muscularis, the Peyer's patches
      and the mesenteric lymph nodes at 6 and 12 hours following intestinal
      manipulation and injection of LPS. There was an upregulation of the costimulatory
      molecules major histocompatibility complex II, CD40, CD80, CD86, and CD205 in the
      DC after intestinal manipulation. CCR-2, CCR-5, CCR-7, CCL-19, and interleukin
      12a were upregulated in a time- and tissue-dependent manner. CONCLUSION:
      Intestinal manipulation or LPS challenge induced a recruitment of DC into the
      muscularis externa and mesenteric lymph nodes combined with an upregulation of
      costimulatory immunocompetent molecules and migratory surface markers in DCs.
      These findings demonstrate a precondition for an immunologic response and a
      possible immunologically mediated gastrointestinal field effect.

PMID- 16908291
TI  - Incidence of graft rejection in small bowel transplanted pigs after
      immunosuppression withdrawal.
AB  - As intestinal grafts require heavy immunosuppression, there are no reports of
      immunosuppression withdrawal after clinical small bowel transplantation. In this
      large-animal study, we investigated the occurrence of graft rejection in
      intestinal-transplanted pigs after withdrawal. Large-White unrelated piglets were
      transplanted and divided in three groups: group 1 (n = 5), intestinal
      transplantation (ITx) with no immunosuppression; group 2 (n = 7), Itx and 60 days
      of treatment with tacrolimus and mycophenolate mofetil; group 3 (n = 5), Itx and
      donor bone marrow infusion (DBMi) and 60 days of treatment with tacrolimus and
      mycophenolate mofetil. Follow-up time after withdrawal was 120 days. Group 1 pigs
      died of graft acute cellular rejection (ACR) after a median of 11 days. In group
      2, two pigs died of ACR-related infection and another two of ACR within 90 days.
      The remaining three animals (43%) were sacrificed at day 180, and their grafts
      showed no signs of ACR. In group 3, two pigs died of ACR-related infection and
      one of graft versus host disease within 80 days; at day 180 the two surviving
      animals showed signs of chronic rejection in the allograft. This study
      demonstrates that total withdrawal after ITx is followed by sudden and lethal ACR
      (or ACR-related infection) in more than 50% of the recipients. When a tolerance
      inducing strategy as DBMi is applied, lethal graft versus host disease may also
      occur. In group 3, the intestinal allograft, to which the recipients were
      partially tolerant, developed chronic rejection that was probably associated with
      a decline with time of donor-leukocytes chimerism, as recently demonstrated in
      rats.

PMID- 16908292
TI  - Mechanism and impact of organ harvesting and ischemia-reperfusion injury within
      the graft muscularis in rat small bowel transplantation.
AB  - INTRODUCTION: Inflammatory events within the gut muscularis contribute to
      dysmotility. We hypothesized that manipulation during organ harvesting initiated
      an inflammatory response via muscularis macrophages and that this cascade was
      amplified during reperfusion. METHODS: Small bowel transplantation was performed
      in Lewis rats. To investigate the impact of organ harvesting on muscularis
      inflammation, cold whole-body perfusion was performed after versus prior to organ
      harvesting. The role of macrophages was investigated by transplantation of the
      macrophage-depleted gut. Leukocyte infiltration was investigated in muscularis
      whole mounts. Mediator mRNA expression was determined by real-time reverse
      transcriptase polymerase chain reaction. Contractility was assessed in a standard
      organ bath. RESULTS: Organ harvesting and ischemia-reperfusion induced leukocyte
      recruitment and mRNA upregulation in the muscularis: interleukin-6 12217-fold,
      monocyte chemoattractant protein-1 62-fold, ICAM-1 12-fold, cyclooxygenase-2: 8
      fold, iNOS: 150-fold. Although organ harvesting with cold ischemia prevented
      early gene expression, peak expression at 3-hour reperfusion was not changed by
      modification of the harvesting technique. Compared to controls, transplanted
      animals showed a 63% decrease in smooth muscle contractility. In contrast,
      transplanted macrophage-depleted gut exhibited significantly fewer leukocytes and
      only a 16% decrease in contractility. CONCLUSIONS: Gut manipulation during organ
      harvesting initiates an inflammatory response within the muscularis that is
      massively intensified during reperfusion. This change contributes to muscular
      dysfunction. Furthermore, the results suggested that resident macrophages play a
      key role in initiating this process.

PMID- 16908293
TI  - FK506 induces the atrophy of enteric ganglia in small bowel transplantation,
      which can be prevented by the neuropeptide bombesin.
AB  - PURPOSE: FK506, which is widely used for immunosuppression, is reported to have
      neurotoxicity. However, its neurotoxicity for transplanted graft enteric ganglia
      (TGEG) has never been reported. The aim of this study was to investigate whether
      FK506 has a neurotoxic effect on TGEG, and whether bombesin (BBS) prevents such
      atrophy. METHODS: Eighteen rats that underwent syngertic heterotopic small bowel
      transplantation (SBTx) using a cuff method were divided into three groups of six
      rats each; A: SBTx alone, B: SBTx with FK506, C: SBTx with FK506/BBS. Either BBS
      (10 mg/kg/d) or normal saline was infused continuously from day 14 to 28. Rats in
      groups B and C were administered FK506 (0.32 mg/kg/day, intramuscularly) daily.
      Analysis of TGEG was performed using immunohistochemistry with protein gene
      product (PGP) 9.5. The ganglionic number was obtained by counting PGP9.5-positive
      ganglia in each graft. RESULTS: The number of TGEG were reduced significantly in
      group B (51.5 +/- 7.7 ganglia per cross section (G/CS)) compared with group A
      (69.7 +/- 6.0 G/CS), but were well preserved in group C (84.8 +/- 10.2 G/CS).
      There were significant differences between groups B and C (P < .001) and also
      between groups A and C (P < .001). CONCLUSION: FK506 showed severe neurotoxicity
      on transplanted grafts, and bombesin could rescue TGEG against FK506
      neurotoxicity.

PMID- 16908294
TI  - Neuroendocrine-immune modulation may be useful for allograft-specific
      immunosuppression in small bowel transplantation.
AB  - PURPOSE: The authors have previously demonstrated that the neuropeptide bombesin
      (BBS) prevented allograft mucosal atrophy under tacrolimus (TRL)
      immunosuppression for rats small bowel transplantation (SBT). The present study
      investigated whether BBS had immunosuppressive effects on small bowel allografts.
      METHODS: Allogeneic SBT was performed heterotopically in rats (n = 12) that
      received daily administration of 0.1 mg/kg/d TRL from postoperative day 0 to day
      14. Rats divided into two groups of six rats each were administered BBS or normal
      saline as a control. Biopsy of the allograft was performed from the stomal site
      on postoperative days 6, 10, and 14. The state of the graft mucosal villi was
      evaluated by H & E staining and TUNEL immunohistochemistry. RESULTS: By
      postoperative day 14, extensive mucosal destruction accompanied by heavy
      transmural cellular infiltration had developed in the control group. Lymphocytes
      and plasma cells infiltrated the lamina propria of the allograft without the
      distorting villous architecture in the BBS group. The TUNEL index of graft mucosa
      in the control group was 1.26% +/- 0.37% (mean +/- SD) and that in the BBS group,
      0.59% +/- 0.20%, respectively (p < .001). CONCLUSION: This study demonstrated an
      immunosuppressive effect of bombesin on transplanted allografts, which might
      dramatically reduce the dose of TRL required for postoperative immunosuppression.

PMID- 16908295
TI  - Absorption of orthotopically transplanted intestine in rats: evaluation of amino
      acid absorption.
AB  - During the early phase of our intestinal transplant program, a low-lipid, amino
      acid-based feeding was employed for most recipients. However, relatively little
      is known regarding the amino acid absorption by a graft following intestinal
      transplantation. Sixty Wistar rats were randomly divided into two groups (n =
      30). The animals received two-step orthotopic intestine transplantation (OIT), or
      the control; enterectomy with anastomoses. We measured mucosal Na(+)/K(+)-ATPase
      and intestinal absorption using stable isotope techniques in vivo. Compared with
      controls, mucosal Na(+)/K(+)-ATPase activity in OIT decreased by 38.3% and 38.4%
      at 2 and 4 weeks, and returned to baseline and control group values at 8 weeks.
      Glycine absorption decreased at 2 weeks and returned to baseline at 4 weeks in
      OIT compared with that in controls. These results suggested that absorption as
      assessed by mucosal Na(+)/K(+)-ATPase and glycine, returned to baseline at least
      4 weeks after transplantation.

PMID- 16908296
TI  - The effect of a valine-rich diet on intestinal adaptation to massive small bowel
      resection in the rat.
AB  - BACKGROUND/PURPOSE: Recently, valine, which is one of the branched chain amino
      acids, has been reported to enhance liver regeneration after hepatectomy in the
      rat. The aim of this study was to investigate the effect of enteral valine
      supplementation on intestinal adaptation. MATERIALS/METHODS: Seven-week-old male
      Lewis rats underwent a 90% small bowel resection. The rats were randomly divided
      into two groups: group V (valine-rich diet) and group S (standard rat chow),
      according to the diet. The rats were sacrificed at the operation day and on
      postoperative days (POD) 7, 14, 30, and 60. The metrics were body weight (BW),
      blood amino acids, urine organic acids, and morphology of the residual small
      intestine. RESULTS: The BW and the intestinal wet weight, jejunal crypt depth,
      and proliferating cell nuclear antigen-positive cells in group V at POD 7 were
      significantly higher than those values in group S, while those in group V at POD
      30 and 60 were smaller than those in group S. The urine methylmalonic acid (MMA)
      level in group V at POD 30 and 60 was much higher than in group S. CONCLUSION:
      Valine enhanced intestinal adaptation after massive small bowel resection in the
      acute phase. However, the long-term supplementation disturbed intestinal
      adaptation, which might be due to the high production of MMA.

PMID- 16908297
TI  - Can bacterial translocation be a beneficial event?
AB  - Infection is a major concern in intestinal transplant recipients. Bacterial
      migration to extraintestinal sites is a central component of the gut hypothesis
      of sepsis. However, some studies have cited the beneficial effects of bacterial
      translocation (BT) on the host acquired immune system. We evaluated the role of
      previous BT on a subsequent BT challenge, examined the BT index in organs as well
      as changes in white blood cell (WBC) count in mesenteric lymph and blood for
      correlation with outcomes. Wistar rats (n = 60) were divided into a BT group (n =
      20), which underwent inoculation of 10 mL of 10(10) CFU/mL Escherichia coli R-6
      confined to the small intestine as opposed to a BT1-14 group (n = 20), which
      underwent the BT procedure on days 1 and 14 or a S1-BT14 group (n = 20) that
      received 10 mL of saline on day 1 and the BT procedure on day 14. Half of the
      animals were killed 2 hours following the BT procedure. Samples from different
      compartments were collected for culture. Mesenteric lymph and peripheral blood
      were examined for WBC counts. The other half of the hosts was subjected to
      outcome evaluation concerning weight gain and mortality. Animals undergoing
      double BT showed a significantly lower index of bacterial recovery (liver,
      spleen, and blood) compared with those having a single BT (P < .05). The WBC
      count of mesenteric lymph cells after double BT was similar to naive animals, but
      significantly lower than the single BT group (P < .05). The outcome was unchanged
      among double BT versus other groups. A previous BT challenge was efficient to
      generate a host-defense mechanism against a second BT episode induced by
      intestinal overgrowth with the same bacterial strain.

PMID- 16908298
TI  - Predicting outcome of procedures to slow intestinal transit.
AB  - Procedures designed to slow intestinal transit in patients with the short-bowel
      syndrome (SBS) have unpredictable outcomes. Our aim was to evaluate the outcome
      and predictive factors for this complication in SBS patients. Ten patients (37-61
      years) underwent reversed segment (n = 9) or nipple valve creation (n = 1). All
      patients had remnant lengths over 90 cm and rapid intestinal transit times. All
      subjects had benign diseases, including Crohn's (n = 3). Six patients had a colon
      remnant. SBS had been present for 8 to 150 months. Nine (90%) required parental
      nutrition (PN) preoperatively. A procedure was performed either alone (n = 5) or
      concurrently with an ostomy closure (n = 3), an ostomy revision (n = 1), or a
      fundoplication (n = 1). There was one postoperative complication (urinary tract
      infection) and no deaths. Two patients developed bacterial overgrowth. One
      required repair of an ileocolonic stricture. One reversed segment was taken down
      12 months later. Five (50%) patients improved (off PN), five remained on PN or
      had persistent diarrhea. Patients with a successful outcome were more likely to
      have had ostomy takedown (60% vs 0%). The duration of SBS; presence of Crohn's
      disease, a colon remnant, or type 1 anatomy; and the transit times were similar
      in both groups. Adjusted remnant length (small intestine +30 cm for type 2
      anatomy and +60 cm for type 3) was similar (136 +/- 20 vs 154 +/- 25 cm).
      Procedures may benefit half of selected SBS patients with adequate remnant length
      and rapid transit. Successful patients are more likely to have an ostomy
      takedown, but the outcome is less determined by transit time or intestinal length
      if over 90 cm.

PMID- 16908299
TI  - Simplified techniques in rat heterotopic small bowel transplantation.
AB  - AIM: Establish a simplified heterotopic small bowel transplantation (SBT) in the
      rat. METHODS: Ninety pairs of male Wistar rats were used as donors and
      recipients. The whole small intestine with a vascular pedicle composed of
      superior mesenteric artery (SMA) and portal vein (PV) was harvested as the graft.
      Revascularization was accomplished by end-to-side anastomosis between donor SMA
      and recipient infrarenal aorta and cuffed end-to-end anastomosis between donor PV
      and left renal vein of recipient. The distal end of graft was exteriorized to
      form an enterostoma. RESULTS: Average time of an operation was 130 minutes and
      the mean warm ischemia time of grafts was 30 minutes. The technical success rate
      of this model was 100% and 7-day survival was 95.6% (86/90). CONCLUSION: This
      simplified technique was effective and practical to improve the outcome of rat
      heterotopic SBT.

PMID- 16908300
TI  - Small bowel and colon transplantation in rats using porto-portal cuff
      anastomosis.
AB  - Portal versus systemic venous drainage and colon grafting are major controversies
      in the techniques of intestinal transplantation. The rat is the best animal for
      research in this field. Nevertheless, this model requires complex microvascular
      anastomoses that are responsible for the high incidence of technical failures. A
      cuff technique is an easier anastomosis method than a hand-suture. We describe a
      simplified rat model of small bowel and colon transplantation using a porto
      portal cuff anastomosis. DONOR: The entire small bowel, cecum, and ascending
      colon are harvested on a vascular pedicle, consisting of a long aortomesenteric
      conduit and portal vein. The right colonic vessels are preserved. The graft is
      flushed and a cuff device is placed on the end of the portal vein. RECIPIENT: The
      graft is implanted through an end-to-side aorto-aorta hand-sewn anastomosis. A
      segment between the first and second jejunal branch is isolated between clamps to
      insert into the portal cuff. After reperfusion, the recipient's mesentery is
      divided just below the cuff anastomosis. The recipient jejunum, ileum, and
      ascending colon are removed en bloc, and the graft is anastomosed in continuity
      with the remaining naive intestine concluding the operation. This simplified
      technique surmounts the technical obstacles in rats because it is easily and
      quickly performed, maintaining the physiological portal drainage, preserving
      graft ileocecal valve and ascending colon, and reaching acceptable success after
      a short period of training.

PMID- 16908301
TI  - Experimental evaluation of Surgisis as scaffold for neointestine regeneration in
      a rat model.
AB  - The aim of the study was to evaluate the use of Surgisis (Cook Biotech Inc.), a
      porcine derived extracellular matrix already used in tissue engineering, as a
      scaffold for neointestinal regeneration in a rat model. A 3-cm length of tubular
      Surgisis graft was interposed with bilateral anastomoses in the middle of an
      isolated ileal loop of Sprague Dawley rats with an ileostomy. The grafts were
      harvested and analyzed using histology and immunohistochemistry at 24 weeks after
      operation. Macroscopic examination revealed neither stenosis nor adhesions in the
      area surrounding the neointestine. The regenerated small bowel showed a mean
      shrinkage of 30.7% (range 20%-40%). Histologic and immunohistochemical evaluation
      showed a well-developed three layers of mucosa and smooth muscle and serosa in
      the regenerated bowel wall that were similar to those of the normal bowel with
      evident neovascularization. Also, the regeneration of smooth muscle fibers and
      innervation were evident. The preliminary results of this study showed that
      Surgisis allowed rapid regeneration of mucosa and smooth muscle and therefore may
      be a promising material for the creation of a neointestine.

PMID- 16908302
TI  - A novel approach for intestinal elongation using acellular dermal matrix: an
      experimental study in rats.
AB  - We tested the hypothesis that an anatomic scaffold placed in continuity with
      viable bowel might allow intestinal growth. Male ACI rats were used for the
      study. Acellular human dermis in the form of tubular scaffolds with an
      intraluminal diameter of approximately 0.3 cm was oriented with the luminal
      basement membrane and serosal dermal surface. The small bowel was transected
      approximately 2 cm distal to the ligament of Treitz. The graft was then
      anastomosed in continuity in group A (n = 5) or as a blind-ended pouch to a
      defunctionalized jejunal limb in group B (n = 8). The animals were sacrificed at
      various time points. Histology and immunohistochemistry were used to evaluate
      structural changes. Animals in group A developed peritonitis and were all
      sacrificed within the first week postoperatively. However, all animals in group B
      survived, increasing their body weight similarly to age-matched rats. Tissue
      samples obtained at sacrifice showed a progressively increasing amount of
      cellular infiltrate over time in the matrix. Epithelial regeneration,
      angioneogenesis, and myofibroblast infiltrate were seen at 2 weeks, while well
      formed branching crypts were seen at 4 weeks. Intact mucosa extended across the
      anastomosis to the grafts at 6 months. This study demonstrated an anatomic
      scaffold of acellular matrix allowed mucosal regeneration from viable bowel
      placed in continuity. These findings set the basis for new intestinal elongation
      techniques.

PMID- 16908303
TI  - Relationship between real-time monitoring of the graft motility and mucosal
      histology in swine intestinal transplantation.
AB  - We studied the correlation between the motility and the mucosal histology of the
      small bowel seeking to detect rejection in an early stage by real-time monitoring
      using a swine model. Intestinal transplantation (ITx) was performed
      orthotopically using FK506 immunosuppression. The distal about 20 cm segment of
      the allograft was exteriorized as a Thiry-Vella stoma for biopsies. Strain gauge
      (SG) force transducers were attached to the graft for real-time monitoring of
      graft motility. Pigs without ITx were used as controls (group 1). Rejection was
      classified into four groups by histologic findings: nonrejection (group 2), mild
      rejection (group 3), moderate rejection (group 4), and severe rejection (group
      5). Migrating motor complex (MMC) phase III was analyzed for the following
      parameters: duration, amplitude, interval, motility index, velocity, and
      frequency of propagation. In group 2, all parameters were almost the same as
      those for group 1. In contrast, groups 4 and 5 showed most parameters
      significantly lower than those in group 1. In group 3, the contractility of the
      MMC was not significantly altered, but the frequency of the propagation was
      decreased significantly. In conclusion, graft motility detected by a real-time SG
      method correlated with the grade of mucosal histology. This method is useful to
      detect rejection at an early stage by examining the frequency of MMC propagation.

PMID- 16908304
TI  - An experimental technique to assess the immunologic consequences of segmental
      small bowel transplantation.
AB  - BACKGROUND: The amount of native small bowel required for adequate nutrition is
      variable, but lies between 10% and 20% of full length. Currently, for patients
      requiring small bowel transplantation (SBT), standard practice is to transplant
      the entire small bowel if space permits. Few experimental studies have addressed
      the effect of the length of small bowel transplanted on immune responses and in
      those that have, the amount of mesenteric lymph node (MLN) transplanted has
      always been a potential confounding factor, as have differences between jejunum
      and ileum. METHODS: Full-length and segmental heterotopic rat SBT was performed
      between PVG donor and DA recipients. To transplant reduced length small bowel
      grafts but to exclude immunologic differences between jejunum and ileum, equal
      lengths of bowel were resected from proximal and distal ends in the donor. A
      proportional amount of MLN was carefully dissected using a microvascular
      technique and then excised. Serial serum samples from the transplant recipients
      were tested for anti-PVG (rejection) and anti-DA (graft-versus-host) antibodies
      using a two-color flow cytometric technique, described previously, with the aim
      of looking for differences in immunologic responses to full and segmental grafts.
      RESULTS: We have established a model of segmental SBT that includes a
      proportional amount of MLN and is free from differences between jejunum and
      ileum. Preliminary data have demonstrated the development of circulating anti
      host and anti-graft antibodies with time for both full-length and segmental SBT.

PMID- 16908305
TI  - Induction of short gut syndrome and transplantation in a porcine model.
AB  - Experimental models in small animals have been described for nutritional studies
      after small bowel transplantation for extensive resection. Herein, we compared
      the outcome of transplanted pigs that underwent transplantation after total small
      bowel resection (SBR) with controls without transplantation. METHODS: Twenty-one
      Landrace pigs (mean weight 30 kg) were assigned to 1 of 3 groups: group 1 (n = 6)
      underwent 80% SBR; group 2 (n = 9), total bowel resection; and group 3 (n = 6)
      total resection plus small bowel transplantation. Postoperative evaluation
      included biochemical analyses, weights, and evaluation of clinical status.
      Conventional endoscopies with graft biopsies were obtained every 4 days to assess
      rejection. RESULTS: Group 1 showed increased body weight after 3 weeks due to
      bowel adaptation, whereas groups 2 and 3 lost weight, an observation that
      correlated with biochemical analyses. Median survival in group 3 was 10 +/- 2
      days; all hosts died of sepsis related to severe acute rejection. DISCUSSION:
      Short gut syndrome appeared in group 2 but not in group 1, where intestinal
      adaptation was observed by 4 weeks after the resection. Rejection was confirmed
      in group 3 using conventional endoscopy plus biopsies and at necropsy.
      CONCLUSION: Total bowel resection is an adequate model for short gut syndrome in
      pigs, rejection can be readily identified by using conventional endoscopy.

PMID- 16908306
TI  - Perioperative analgesia in experimental small bowel transplantation.
AB  - BACKGROUND: Despite numerous studies in experimental rat small bowel
      transplantation (SBT), few authors make reference to perioperative analgesia.
      Recent changes to the Animals (Scientific Procedures) Act 1986 in the United
      Kingdom have made the use of analgesia in laboratory animals compulsory because
      pain is unnecessary in the majority of scientific procedures. METHODS:
      Heterotopic SBT (PVG-->DA) was performed on male rat recipients weighing 220 to
      250 mg under isoflurane with a mean anesthetic time of 100 minutes. Recovery from
      anesthesia was usually within 15 minutes. Analgesia regimens were based on those
      in common use for other procedures. All drugs were administered in the 30 minutes
      prior to recovery from anesthesia. Group A received carprofen (2 mg/kg IM or SC).
      Group B was given buprenorphine (0.05 mg/kg either IM or SC). Group C received
      paracetamol (10- 30 mg) rectally. An early postoperative scoring system of four
      criteria was used, giving a maximum (least desirable) score of 16. Sixty
      transplants were performed, divided between the three groups. RESULTS: In group A
      animals scored a median of 1 of 16 but all except three recipients died within 3
      hours. Those in group B scored a median of 8 of 16, but all animals except one
      died between 4 to 16 hours after surgery. Group C had a median score of 11 of 16,
      but there was no early mortality. Postmortem examination excluded technical
      failures in all but three animals. CONCLUSION: We recommend the use of
      paracetamol for perioperative analgesia in SBT because of the high mortality
      associated with other drugs when used in this procedure.

PMID- 16908307
TI  - Living unrelated donation: tackling the problem with a wrong strategy.

PMID- 16908308
TI  - Cadaveric donor factor variations during a 12-year period: influence on kidney
      transplant outcomes.
AB  - Our purpose was to evaluate changes in cadaveric donor factors between 1993 and
      2004 and their impact on the short- and long-term outcomes of renal transplants
      in a single center. PATIENTS AND METHODS: Cadaveric renal transplants performed
      in our unit between 1993 and 2004 were divided in two groups of identical length:
      A (n = 455; 1993-1998) and B (n = 465; 1999-2004). Major differences related to
      donor, graft, and recipient factors were analyzed between groups and correlated
      with main outcome parameters. Recipient age, gender, weight, etiology of end
      stage renal disease, average length of dialysis, and cold ischemia were not
      different in the two periods. RESULTS: Grafts harvested in our hospital were more
      frequent in group A (92.3 vs 78.2%; P < .005). Traumatic causes of death were
      more frequent before 1999: 90.9 vs 70.9% (P < .001). Mean donor age was higher
      after 1999: 31.37 vs 35.94 years (P < .005). Female donors were more frequent in
      the second period: 20.5 vs 26.6% (P < .05). Mean donor weight was also higher:
      52.36 vs 67.86 kg (P < .05). All of these differences were unfavourable
      characteristics regarding graft outcomes. Delayed graft function (A = 13%, B =
      24.2%), acute rejection episodes (A = 41.2%, B = 28%), and chronic allograft
      dysfunction (A = 23.5%, B = 14.4%) were also significantly different between the
      two cohorts (P < .005). Graft function (serum creatinine at 1 and 2 years),
      patient and graft survivals, causes of graft loss, and of patient death were
      similar across time. CONCLUSION: The unfavorable tendency in the quality of
      cadaveric donors during the last 12 years had no negative impact on graft
      function and patient outcome.

PMID- 16908309
TI  - Hand-assisted laparoscopic nephrectomy in living donors.
AB  - Hand-assisted laparoscopic nephrectomy (HLN) in living donors is a minimally
      invasive surgical modality that uses classic laparoscopic techniques either
      combined or not with the use of the surgeon's hand as a support tool during renal
      dissection maneuvers. The purpose of this study was to describe the initial
      experience with HLN technique in renal donors. Among 58 hand-assisted
      laparoscopic nephrectomies, the left kidney was removed in 39 donors (67%) and
      the right in 19 (33%). Surgery time ranged from 55 to 270 minutes (mean 156.9 +/-
      49.5). Warm ischemia time ranged from 2 to 11 minutes (mean 4.38 +/- 2.31 min),
      with an estimated mean blood loss during the intraoperative period of 268 mL.
      Conversion to open surgery was required for four (6.8%) patients due to a
      vascular lesion. Upon graft evaluation, we observed immediate diuresis in 56
      (96.3%) cases, with a mean serum creatinine on postoperative day 7 of 1.74 +/-
      1.61 mg/dL. Renal vein thrombosis requiring graft removal occurred in one (1.7%)
      patient. Lymphocele was observed in three recipients (5.1%), and urinary leakage
      due to ureteral necrosis in three cases (5.1%). HLN for living donors is a safe
      procedure and an effective alternative to open nephrectomy. In this series, the
      procedure displayed low morbidity after surgery, providing a good morphological
      and functional quality of the graft for the recipient.

PMID- 16908310
TI  - Randomized clinical assay for hepatic grafts preservation with University of
      Wisconsin or histidine-tryptophan-ketoglutarate solutions in liver
      transplantation.
AB  - University of Wisconsin (UW) solution has been the standard for preservation of
      liver transplantation grafts since 1989. However, some studies demonstrated that
      histidine-tryptophan-ketoglutarate (HTK) solution is also effective. The purpose
      of this study was to compare the efficacy of both solutions in liver
      transplantation. From January 2003 to August 2004 the livers of deceased donors
      were randomized into HTK and UW groups. The 102 studied patients included 65
      (63.7%) in the UW group and 37 (36.3%) in the HTK group. Sex, race, hemodynamic
      state, use of adrenergic drugs, and presence of steatosis in the donor were
      similarly distributed in the two groups (P > .05). The mean age of the donors was
      38.1 years (SD +/-14.4) in the UW group and 44.6 years (SD +/-14.2) in the HTK
      cohort (P = .036). Sex, race, age, etiology of the cirrhosis, retransplant, acute
      liver failure, portal thrombosis, and Child-Pugh and MELD scores in the
      recipients were similarly distributed in the two recipient samples (P > .05).
      Among 89 patients who completed 4 months of follow-up, the HTK group included
      eight cases (25.8%) of biliary complications versus five cases (8.6%) in the UW
      group (P = .033; OR = 2.0 95% CI = 1.2-3.5). The incidence of graft dysfunction
      was 2.8% in the HTK group and 9.4% in the UW group (P = .15). In conclusion, UW
      and HTK solutions were equally effective for the preservation of the hepatic
      graft. The routine use of HTK solution can reduce the costs of liver
      transplantation.

PMID- 16908311
TI  - Apoptosis and nuclear proliferation in rat small bowel submitted to hypothermic
      hyperbaric oxygenation for preservation.
AB  - This study was conducted to assess apoptosis and nuclear proliferation in rat
      small bowel submitted to hypothermic hyperbaric oxygenation for preservation.
      METHODS: Twenty two-month-old, male Wistar rats, weighing 250 g were divided into
      two groups: group I (n = 10), in which the small bowel was preserved for 12
      hours, and group II (n = 10) in which the small bowel was preserved for 24 hours.
      After vascular and intraluminal perfusion, 3-cm segments were maintained in
      Ringer's solution at 2 degrees to 4 degrees C under normobaric conditions (groups
      Ia and IIa) or conditioned in a small hyperbaric metal chamber with 100% oxygen
      at 5.5 absolute atmospheres (groups Ib and IIb). After 12 or 24 hours, apoptotic
      and mitotic indices were evaluated by immunohistochemical methods. RESULTS: The
      apoptotic index was significantly higher in small bowel segments in groups Ia and
      IIa compared with groups Ib and IIb. The mitotic index was significantly higher
      among group IIb. CONCLUSION: Hypothermic hyperbaric oxygenation reduced
      intestinal epithelial apoptosis and increased nuclear proliferation during rat
      small bowel preservation.

PMID- 16908312
TI  - A novel system for organ and tissues preservation: the refrigerating hyperbaric
      chamber.
AB  - This study was designed to investigate the feasibility of building a simple and
      inexpensive device to preserve organs or tissues in hyperbaric and hypothermic
      conditions. METHODS: The device was built on a 40-cm wide, 28-cm long, and 23-cm
      deep stainless steel chassis. The pressure vessel was built by a 7.8-cm bore
      stainless steel cylinder put inside another 12-cm cylinder welded together and
      closed by a steel plate on the top and bottom. The inferior plate was welded, and
      the superior one was fixed by manual clasp nut. The cooling system is made up of
      air compressor, condenser, expansion area, and cooling worm that is located
      between the cylinders. The temperature-controlling device is a computer processor
      contained in an integrated-circuit chip, with a on-off system to maintain the
      chamber temperature between 2 degrees to 4 degrees C. The compression of the
      chamber is performed by lateral coupling with the oxygen cylinder and is
      maintained at 5.5 absolute atmospheres and controlled by air pressure gauge. The
      maximal work pressure was evaluated by spreadsheet. Temperature or pressure
      changes were evaluated by 12- and 24-hour assays. RESULTS: The maximal work
      pressure permitted was 6.5 absolute atmospheres. Thus, the container was free
      from danger. The temperature inside the chamber was kept between 2 degrees and 4
      degrees C. The production costs of the prototype was US$1000. DISCUSSION: The
      manufacture of the refrigerating hyperbaric chamber is viable, simple, and
      inexpensive.

PMID- 16908313
TI  - Renal transplantation in patients over 60 years of age: a single-center
      experience.
AB  - The prevalence of end-stage renal disease (ESRD) increases with advancing age. In
      most countries renal transplant recipients are getting older, too.
      Transplantation must be considered for ESRD patients older than 60 years;
      however, there are few data regarding outcomes in this population. We
      retrospectively reviewed the clinical course of recipients aged > or =60 years (n
      = 43) who underwent primary or repeated grafts from August 1988 to December 2004.
      We then compared recipient and donor characteristics as well as graft and patient
      survivals with recipients aged 18 to 59 years (n = 1058) who were transplanted
      during the same time. Donor age tended to be higher among the oldest recipient
      group (P < .001). Mean follow-up was significantly shorter in the group aged > or
      =60 years (P < .001), as our institution only recently has frequently accepted
      patients > or =60 years. Older recipients showed more frequent delayed graft
      function (P = .007), longer initial hospitalization (P = .005), and a
      significantly lower incidence of posttransplant acute rejection episodes (P =
      .015). Patient (P = .057), graft (P = .407), and death-censored graft (P = .649)
      survivals were not different between the two groups. Seven recipients aged > or
      =60 years died; the main cause of which was cardiovascular in origin. The loss of
      organs (n = 11) in the older patients was mainly due to death with a functioning
      kidney (54.5%). Our results confirm that renal transplant must be considered in
      selected patients older than 60 years as patient and graft survivals are similar
      to those of younger patients.

PMID- 16908314
TI  - Impact of hepatitis C virus on renal transplantation: association with poor
      survival.
AB  - Data concerning the effect of hepatitis C virus (HCV) infection on the long-term
      outcome of patient and allograft survival are conflicting. We performed a
      retrospective study including all renal transplant recipients who underwent the
      procedure at our center between July 1983 and December 2004. We compared HCV
      positive (n = 155) versus HCV-negative (n = 1044) recipients for the prevalence
      of anti-HCV, patient/donor characteristics, and graft/patient survival. The
      prevalence of HCV-positive patients was 12%. The anti-HCV positive recipients
      displayed a longer time on dialysis (P < .001), more blood transfusions prior to
      transplant (P < .001), and a higher number of previous transplants (P < .001).
      There were no differences in the incidence of acute rejection between the two
      groups. Patient (P = .006) and graft survival (P = .012) were significantly lower
      in the HCV-positive than the HCV-negative group. Graft survival censored for
      patient death with a functioning kidney did not differ significantly between HCV
      positive and HCV-negative recipients (P = .083). Death from infectious causes was
      significantly higher among the HCV-positive group (P = .014). We concluded that
      HCV infection had a significant detrimental impact on patient and renal allograft
      prognosis. Death from infectious causes was significantly more frequent among HCV
      positive than the non-HCV population.

PMID- 16908315
TI  - Effect of thymoglobulin in graft survival and function 1 year after kidney
      transplantation using deceased donors.
AB  - This study evaluated 1-year graft function and survival among kidney
      transplantations from deceased donors using thymoglobulin (Thymo) as an induction
      strategy. PATIENTS AND METHODS: Fifty-seven percent of patients were men and
      overall mean age was 42 +/- 15 years. Cold ischemia time was 20.1 +/- 4.8 hours.
      The primary outcome was defined as survival not censored for death after 1 year.
      The secondary outcome was defined as a comparison of function and survival among
      patients who received more or less then six doses of Thymo. RESULTS: Four
      patients experienced acute rejection episodes and the other three died during
      follow-up. One-year graft survival was 91% with a mean serum creatinine of 1.28
      +/- 0.43 mg/dL. Cytomegalovirus infection occurred in 56%. Forty-two (64%)
      patients displayed acute tubular necrosis of mean duration of 6.89 +/- 7.48 days.
      Patients who received lower doses showed better serum creatinine values 3 months
      (1.45 vs 1.86 mg/dL, P = .013) and 12 months (1.05 vs 1.50 mg/dL, P = .04). The
      difference was probably due to acute tubular necrosis that produced a RR of 1.7
      (P = .02; CI 1.04-2.97) when compared with patients with Scr values above 1.30
      mg/dL. When censored for death, graft survival was not different between the two
      groups (< or =6 doses 93% vs >6 doses 97%, P = .43). CONCLUSION: Immunologic
      induction with Thymo produced excellent graft survival after 1 year with
      preservation of graft function. Delayed graft function was the most important
      determinant of graft function after 1 year.

PMID- 16908316
TI  - Evaluation of apoptosis in peripheral blood lymphocytes of renal transplant
      patients.
AB  - The aim of this study was to evaluate the occurrence of apoptosis and the
      expression of FasL and IL-2 genes in apoptotic peripheral blood mononuclear cells
      (PBMC) at different posttransplant periods. Three groups of patients were
      studied: group 1, kidney transplant recipients at least 1 year posttransplant (n
      = 17); group 2, kidney transplant recipients at least 5 years posttransplant (n =
      15); and a control group composed of 7 healthy subjects. Apoptosis was detected
      by annexin flow cytometry and gene expression by reverse transcription polymerase
      chain reactions. The percentage of apoptotic cells was significantly higher in
      groups 1 (42 +/- 4%) and 2 (37 +/- 3%) than the controls (27 +/- 2%; P < .0001).
      Apoptotic cells in group 1 was significantly higher than in group 2 (P < .005). A
      significant difference in FasL expression was observed between groups 1 and 2 (P
      < .001) and the immunosuppressive regimen. These findings suggest that PBMC of
      kidney transplant recipients are more susceptible to activation-induced cell
      death and that the Fas-FasL pathway is involved in this process.

PMID- 16908318
TI  - Plasmapheresis for recurrent posttransplant focal segmental glomerulosclerosis.
AB  - The high recurrence rate of focal segmental glomerulosclerosis (FSGS) in kidney
      transplant recipients suggests that such patients have a circulating factor that
      alters glomerular capillary permeability. Serum from patients with FSGS increases
      glomerular permeability to albumin. This permeability factor has been partially
      identified as a protein. The removal of this protein by plasmapheresis (PP)
      decreases proteinuria. In this study we report data on the therapeutic effects of
      PP in FSGS children with recurrence in the transplanted kidney. Three hundred
      pediatric (age <19 years) renal transplants were performed, including 21 patients
      (24 transplants) with FSGS as a cause of renal failure. Fourteen (58.3%) subjects
      experienced disease recurrence (proteinuria >1 g/m(2) per day) within 1 month
      after transplantation. Mean age patient was 12 +/- 4.3 years, including 83.3%
      Caucasians and 70.2% recipients of living donor grafts. Nine were treated with 10
      cycles of PP (3 cycles/weekly), initiated immediately after recurrence (<48
      hours). Immunosuppression included high doses of cyclosporine (C(2) levels of
      1700-1800 ng/mL), mycophenolate sodium or mofetil, and prednisone. Thirteen
      patients were induced with anti-IL2 receptor monoclonal antibody
      (daclizumab/basiliximab). Among the patients who underwent PP, five (55.5%)
      achieved a complete remission and one (12%), a partial remission (1 g/24 hours).
      There were no cases of remission among the five patients who were not treated
      with PP. Those who achieved remission after PP experienced no recurrences during
      the 2.6 +/- 1.4 years follow-up. PP appears to be effective to treat recurrent
      FSGS following kidney transplantation. It should be started as soon as possible.

PMID- 16908317
TI  - Conversion to sirolimus in pediatric renal transplantation recipients.
AB  - We retrospectively evaluated the efficacy and safety of sirolimus (SRL) in 16
      pediatric renal transplant recipients, who were 9.4 +/- 4.1 years of age when
      they first received SRL. The indications for SRL therapy were rescue from steroid
      resistant acute rejection (31.3%), neoplasia (31.3%), diabetes (12.5%),
      polyomavirus-associated nephropathy (6.3%), chronic allograft dysfunction (6.3%),
      calcineurin inhibitor nephrotoxicity (6.3%), and hemolytic uremic syndrome
      (6.3%). Mean follow-up after the switch to SRL was 17.7 +/- 15 months. The final
      immunosuppression was CNI + SRL + prednisone (PRED) in five patients, SRL + PRED
      in six, SRL + mycophenolate mofetil (MMF) + PRED in four, and SRL + MMF in one.
      The use of SRL in these selected pediatric renal recipients was successful,
      except when creatinine was high at the moment of conversion. Further studies are
      necessary to assess the beneficial outcomes versus adverse events among the
      pediatric transplant population receiving SRL for immunosuppression.

PMID- 16908319
TI  - Twenty years of liver transplantation in Brazil.
AB  - This paper summarizes the 20 years of liver transplantation in Brazil, in the
      context of the Western world scenario. More than 5000 liver transplantations have
      been performed in the country since September 1, 1985. The living-donor liver
      transplantation, one of the landmarks in liver transplantation, was first
      described by our team in 1989. Brazil is the seventh country in number of liver
      transplants in the Western world and the first in Latin America. Almost 1000
      procedures were performed in 2004, 19% of them involving living donors.

PMID- 16908320
TI  - Results of urgent liver retransplantation in the state of Sao Paulo, Brazil.
AB  - The treatment of end-stage liver disease includes transplantation as a life
      saving procedure although it has serious complications of hepatic artery
      thrombosis, liver dysfunction, or primary nonfunction, which frequently lead to
      the need for retransplantation. According to various reports, the incidence of
      retransplantation is around 10%. Given the critical organ shortage, the chance
      for a second transplant remains a controversial discussion in medical, ethical,
      and economic grounds because patient and graft survival rates after
      retransplantation are lower than those for primary transplantations. We
      retrospectively reviewed all of the urgent liver retransplants from October 2001
      to February 2005 (52 months) by analyzing the number of retransplants, blood
      group, time between first and second liver transplantation, age, sex, and
      mortality. Data were obtained from the Transplantation System, State of Sao Paulo
      Health Secretariat. Among 1252 liver transplants performed during this period, 98
      (7.82%) were urgent retransplantations. The primary procedure employed 955
      (76.28%) deceased donors and 297 (23.72%) living donors. All 98 retransplants
      were performed using an organ from the pool of deceased donors. The retransplant
      rate was acceptable according to the literature, although we observed high rates
      of early mortality (<60 days), leading to a discussion of which patients had a
      better chance of survival and the best time to perform the second transplantation
      to use this scarce and precious resource in the best possible way.

PMID- 16908321
TI  - Therapeutic effect of hyperbaric oxygen in hepatic artery thrombosis and
      functional cholestasis after orthotopic liver transplantation.
AB  - Among the postoperative complications, hepatic artery thrombosis can occur in up
      to 10% of adult orthotopic liver transplants and intervention is indicated when
      this occurs within 30 days by retransplantation. Primary graft dysfunction, which
      can occur in up to 30% of the cases and is another potential complication,
      although reversible, has a relatively high mortality rate. Hyperbaric therapy, an
      efficient mode of tissue oxygenation, is being used in an increasing number of
      clinical situations. We report here two cases where hyperbaric oxygen therapy
      greatly benefited patients with complications after orthotopic liver
      transplantation: one with hepatic artery thrombosis and the other with primary
      graft dysfunction. Both patients showed rapid clinical recovery with gradual
      reduction of liver and canalicular enzymes soon after commencing hyperbaric
      oxygen therapy.

PMID- 16908322
TI  - Carcinosarcoma of the liver: a case report.
AB  - Primary hepatic carcinosarcoma is a rare malignant hepatic tumor containing both
      carcinomatous and sarcomatous elements. A 40-year-old man referred to our liver
      transplant team because of hepatic cirrhosis was on the waiting list, having
      undergone all liver tests, ultrasonography, and with normal serum alpha
      fetoprotein markers every 6 months to search for a tumor. He underwent a liver
      transplantation without complication. The pathologic findings of the original
      liver indicated carcinosarcoma. We have reviewed the literature on this subject.

PMID- 16908323
TI  - Serologic profile in hepatitis B virus and hepatitis C virus in a Brazilian liver
      transplant waiting list.
AB  - Chronic viral hepatitis is currently the most common indication for liver
      transplantation (OLT). Knowing the serological profile of patients on the liver
      transplant waiting list (LTWL) is essential to manage prophylactic and
      therapeutic strategies pre- and post-OLT. The aim of this study was to determine
      the hepatitis B virus (HBV) and hepatitis C virus (HCV) serological profile on
      the LTWL. METHODS: Serological data were collected from 44 candidates included on
      the LTWL from May 2003 to November 2004. HBV and HCV serological profiles were
      performed by microenzyme immunoassay. RESULTS: Twenty-eight patients (66.7%)
      lacked HBV serological markers. Anti-HBs was detected in 9.5% and was positive
      for HBsAg, anti-HBc, IgM anti-HBc, or HbeAg in 4.8% of patients, probably related
      to reactivation of chronic infection. In 7.1% of patients, the markers
      demonstrated serological cure of infection. In HCV patients, 41.5% were positive.
      There was HBV and HCV co-infection in 12.2% of patients. CONCLUSION: HBV
      infection in 21.4% of the patients corroborates the need to use more efficient
      protocols for prophylactic and therapeutic management pre- and post-OLT. The high
      prevalence of HCV infection reinforces the need to follow adequate protocols to
      avoid related complications and guarantee rational and universal use of more
      efficient drugs.

PMID- 16908325
TI  - Impact of cytomegalovirus infection on long-term survival after orthotopic liver
      transplantation.
AB  - Cytomegalovirus (CMV) is one of the most common and serious opportunistic
      infections in solid organ transplant patients. In different series the incidence
      of CMV infection ranges from 25% to 85%. An indirect effect of infection includes
      reduced long-term patient and allograft survival. Our objective was to determine
      the relationship between CMV infection and patient survival after orthotopic
      liver transplantation. PATIENTS AND METHODS: From January 1999 to December 2001,
      163 orthotopic liver transplantations were performed in 154 patients. The
      inclusion criteria for this analysis were the absence of retransplantation and
      survival of more than 6 months. One hundred fifteen patients met the inclusion
      criteria. CMV infection was detected by positive antigenemia. RESULTS: CMV
      infection occurred in 65.8% of patients after orthotopic liver transplantation.
      Their 5-year survival was 85%, with no difference observed between patients with
      or without infection (P = .8). CONCLUSION: CMV infection did not interfere with
      patient survival after orthotopic liver transplantation.

PMID- 16908324
TI  - Risk factors associated with cytomegalovirus infection in orthotopic liver
      transplant patients.
AB  - Our objective was to investigate the potential risk factors associated with
      cytomegalovirus (CMV) infection. PATIENTS AND METHODS: From January 1999 to
      December 2001, 163 liver transplantations were performed in 154 patients. The
      study inclusion criteria were absence of retransplantation and survival of more
      than 6 months. One hundred fifteen patients met the inclusion criteria. We
      determined variables such as age, gender, and number of hemecomponents as well as
      serum IgG CMV status of donors and recipients. We recorded the immunosuppression
      used by each patient. CMV infection was detected by positive antigenemia.
      RESULTS: Recipient mean age was 50 years. The etiology of cirrhosis was viral (n
      = 57; 49.6%), alcoholic (n = 20; 17.4%), virus and alcohol (n = 15; 13.0%),
      cryptogenic (n = 14; 12.2%), or other causes (n = 9; 7.8%). CMV infection was
      positive in 75 patients (65.8%). There was no relation between infection and age,
      gender, or CMV IgG donor recipient status, or the number of hemecomponent units.
      The risk was 3.8-fold higher for patients receiving a three-drug compared with a
      two-drug regimen. When cyclosporine was used instead of tacrolimus, the risk of
      CMV infection was 4.3-fold higher. Logistic regression analysis revealed
      cyclosporine (OD=5.8) and a three-drug regimen (OD=6.7) to have stronger
      associations with CMV infection. CONCLUSION: The use of cyclosporine (OD=5.8) and
      a three-drug regimen (OD=6.7) are risk factors for CMV infection.

PMID- 16908326
TI  - Simultaneous pancreas-kidney transplantation: five-year results from a single
      center.
AB  - We report the 5-year results of our simultaneous pancreas-kidney transplantation
      (SPKT) program, started on May 2, 2000. Forty-two SPKT were performed on 42 type
      I diabetic patients with chronic renal failure. The procedure was performed with
      enteric diversion and vascular anastomosis to the iliac vessels.
      Immunosuppressive protocol included antithymocyte globulin, tacrolimus,
      mycophenolate mofetil, and steroids. The 24 women and 18 men had a mean age of
      33.5 +/- 6.3 years and mean 22.8 +/- 14.2 years time of diabetes evolution. Forty
      patients had been on dialysis for 34.3 +/- 24.1 months, and two were preemptive
      transplantations. Acute rejection episodes were treated in eight patients
      (19.1%): in three cases they affected both organs; in two only the kidney was
      affected; and the other three were pancreas graft rejections. The incidence of
      postoperative complications requiring re-operation was 42.9%, mostly pancreas
      graft related. Two patients died, one due to cardiovascular disease; the other
      was transplant related. Three kidney grafts were lost, and the causes were
      immunologic, thrombosis, and patient death. Pancreas graft loss occurred in seven
      patients: thrombosis (n = 3); infection (n = 3); immunologic (n = 1). The
      patients with surviving grafts were doing well, with normal kidney and pancreas
      function: serum creatinine = 0.89 +/- 0.15 mg/dL; fasting blood glucose = 79 +/-
      16 mg/dL; HbA1c = 4.7 +/- 1.1%. The 1-year patient, kidney, and pancreas survival
      rates were 97.3%, 94.6%, and 83.8% and 5-year values, 91.7%, 89.2%, and 78.7%,
      respectively. In conclusion, these results are similar to the most recent
      UNOS/IPTR reports, leading us to consider our experience with SPKT very positive.

PMID- 16908327
TI  - No induction versus anti-IL2R induction therapy in simultaneous kidney pancreas
      transplantation: a comparative analysis.
AB  - The optimal immunosuppressive regimen for simultaneous kidney pancreas
      transplantation (SKPT) is still not established. We conducted a study to compare
      the safety and efficacy of no induction versus anti-IL-2 receptor induction
      protocols in SKPT recipients receiving the same maintenance regimen. METHODS:
      Sixty-three SKPT recipients were divided into two groups: no induction group (n =
      42) and anti-IL-2 receptor induction group (n = 21). All patients were maintained
      on tacrolimus, mycophenolate mofetil, and prednisone. Primary endpoints were 1
      year acute rejection incidence and patient and graft survivals. RESULTS:
      Demographic characteristics were similar between the groups. Acute rejection
      incidence at 1 year was equal in both groups (28.6%). Kidney and pancreas
      allograft survival in the no induction group were 78.6% and 76.2%, and in the
      anti-IL-2R induction group, 81% and 71.4%, respectively (P = NS). Patient
      survival was also similar: 83.3% in the no induction versus 85.7% in the anti-IL
      2R induction group. Deaths due to sepsis were higher in the anti-IL-2R induction
      group, albeit not significantly. CONCLUSION: The use of a no-induction protocol
      in SKPT is safe and effective immunosuppression that also reduces transplantation
      costs.

PMID- 16908328
TI  - Pancreas retransplantation: outcomes of 20 cases.
AB  - The objective of this paper was to evaluate our initial experience with pancreas
      retransplantation. From January 26, 1996 to February 2005, 285 pancreas
      transplantations were performed, including 20 (7%) retransplants. The causes of
      primary graft loss were graft thrombosis in 11 (55%, 7 venous and 4 arterial); 4
      (20%) chronic rejections; 2 (10%) ischemia/reperfusion injury; 1 severe graft
      pancreatitis; 1 primary nonfunction; and 1 sepsis. Venous drainage was placed in
      the iliac vessels in 14 (70%), vena cava in 5 (25%), and portal drainage in 1.
      The exocrine drainage was vesical in 16 (80%) and enteric in 4 (20%). In 14 cases
      (70%), the primary graft was removed before and in 6 (30%) at the time of
      retransplantation. Immunosuppression was based on antilymphocyte induction,
      tacrolimus, mycophenolate mofetil, and steroids in all patients. One-year patient
      and graft survivals were 95% and 85%. In conclusion, pancreas retransplants were
      feasible with results comparable to a primary pancreas transplantation.

PMID- 16908329
TI  - Influence of pancreas transplantation alone on native renal function.
AB  - Pancreas transplantation alone (PTA) has become an accepted treatment of
      nonuremic diabetic patients, when the risks of secondary complications of
      diabetes mellitus are greater than those of the surgical procedure and the
      posttransplant immunosuppression. As a decrease in native renal function is
      expected, we followed this parameter among patients who underwent PTA. From
      January 1997 through January 2005, we performed 69 PTA in 66 patients. All
      patients showed glucose hyperlability with hypoglycemic unawareness, or two or
      more diabetic complications as well as creatinine clearance (CrCl) > or = 45
      mL/min. Immunosuppression was based on tacrolimus, mycophenolate mofetil and
      prednisone. Twenty-four hour CrCl were performed after all successful PTA. We
      divided patients in two groups according to the pretransplant CrCl: group 1, CrCl
      < or = 70 mL/min (n = 20) and group 2, CrCl > 70 mL/min (n = 25). The data were
      analyzed using Student's t-test (P < or = .05 was considered significant). Twenty
      one patients were excluded from the analysis because of death (n = 5) or graft
      loss (n = 8) during the first year or follow-up shorter than 1 year (n = 8). The
      mean value of CrCl decreased 28.8% (85.0 +/- 31 versus 60.5 +/- 36 mL/min; P <
      .001). There was also a 39.3% reduction among group 1 subjects (P = .003),
      including 10 who displayed CrCl < or = 30 mL/min. There was also a 24.4%
      reduction among group 2 (P = .008), but no patient developed end-stage renal
      disease. In conclusion, native renal function decreased significantly after PTA,
      but was well tolerated among patients with CrCl > 70 mL/min. Patients with CrCl <
      70 mL/min show a significant risk of worsened renal function.

PMID- 16908330
TI  - Experimental training model of pancreas transplant.
AB  - Pancreas transplant (Ptx) is the gold standard for the treatment of type I
      diabetes, mainly when associated with renal failure. The number of Ptx is
      increasing worldwide, but in developing countries, such as Brazil, the number of
      centers is small and transplant surgeons need to practice the technique. METHODS:
      For this model, 21 pancreas harvestings were performed in patient corpses after
      death from extra-abdominal causes, without pancreatic disease and peritoneal or
      systemic infection. The vessels of the grafts were prepared on the backtable
      according to the usual practice in humans. The pancreas was implanted in the
      inferior vena cava and aorta of mixed breed dogs, with 10 exocrine-bladder
      drainage and 11 duodenum-ileal anastomosis. RESULTS: There were anastomotic
      strictures of the portal vein in dogs 1 and 2. There was no arterial stricture or
      large bleeding. None of the animals died until the revascularization of the
      graft. Dogs 2, 5, and 8 died during the exocrine anastomosis. The arterial flow
      was initially high, but at the end of the procedure there were thromboses of
      small arteries. CONCLUSION: The experimental surgical technique model is
      feasible, repeating the stages of clinical pancreatic transplantation and
      allowing the training of surgeons.

PMID- 16908331
TI  - Effect of hyperbaric oxygen on liver regeneration in a rat model.
AB  - Hyperbaric oxygen therapy is a treatment that has been gradually implemented for
      the treatment of several pathologic conditions. The present study evaluated the
      effect of hyperbaric oxygen therapy for hepatic regeneration and its relationship
      to mitochondrial function. Male Wistar rats underwent partial hepatectomy (70%)
      and subsequently underwent two sessions of hyperbaric oxygen (90 minutes each, at
      a pressure of 2 ATA). The animals were sacrificed at 24 and 48 hours after
      surgery. Hepatic regeneration was evaluated by the dry weight of the remaining
      liver, the hepatic regeneration rate, the hepatic DNA content, and the hepatocyte
      proliferation rate using the "proliferating cell nuclear antigen" (PCNA) content.
      Function of the mitochondria was evaluated by its oxygen consumption during
      respiratory states 3 and 4, its respiratory control ratio (RCR), its membrane
      potential, as well as its osmotic swelling. We also measured serum levels of
      aminotransferases. The results revealed an increased dry weight of the remaining
      liver, regeneration rate, and DNA content at 24 and 48 hours after hepatectomy.
      The hepatocyte proliferation rate was significantly higher among animals treated
      with hyperbaric oxygen therapy at 48 hours after surgery. There was no
      significant difference in aminotransferase levels. Mitochondrial respiration
      revealed reduced oxygen consumption in state 3 after 48 hours. These results
      demonstrated that hyperbaric oxygen stimulates hepatic regeneration at 24 and 48
      hours after 70% hepatectomy. The effect of hyperbaric oxygen on hepatic tissue
      occurs without tissue damage and protects mitochondria after 48 hours.

PMID- 16908332
TI  - Functional outcome of bone marrow stem cells: mononuclear versus mesenchymal stem
      cells after cellular therapy in myocardial scar in Wistar rats.
AB  - Experimental studies have suggested that a bone marrow stem cell transplant into
      the heart produces a favorable impact on tissue perfusion, yielding a new
      perspective on myocardial regeneration. Studies in human beings have demonstrated
      an improved clinical and functional cardiac state, which has been explained
      mainly by the angiogenic potential of the stem cells. Our objective was to
      compare the functional outcome of mononuclear stem (MoSC) and mesenchymal stem
      (MeSC) cell therapy after myocardium infarction in rats. Forty-two rats with
      myocardial infarctions underwent autologous transplantation of MoSC and MeSC in
      animals with ejection fractions lower than 40%. The functional analysis was
      performed using echocardiography at baseline and at 1 month after direct
      injection into the ventricular wall using: 5 x 10(6) MoSC (n = 08) or 2.5 x 10(6)
      MeSC (n = 13) or medium controls (n = 21). Statistical significance was accepted
      when P < .05. Intragroup comparisons of baseline versus 1-month follow-up were
      performed with paired t tests. Kruskal-Wallis was used as appropriate. There was
      a difference in baseline left ventricular ejection fraction (LVEF) and left
      ventricular-end dyastolic volume between all groups. After 1 month, LVEF
      decreased in the control group but remained unchanged in MoSC and MeSC groups. In
      all groups we observed myocardial remodeling. In conclusion, we have not
      demonstrated functional effectiveness with either MoSC or MeSC cell type, but
      potentially improved myocardial perfusion needs to be analyzed.

PMID- 16908333
TI  - Proliferation of bone marrow mesenchymal stem cells, skeletal muscle cells and co
      culture of both for cell myocardium therapy in Wistar rats.
AB  - The best results of cell therapy are achieved by a greater quantity of cells,
      delivery to the correct place, and cell conditions of viability with
      proliferation and without apoptosis. The quantification of cellular growth,
      including proliferation and viability, has become an essential tool. The
      objective of this study was to analyze cell proliferation in 14-day cultures of
      bone marrow mesenchymal stem cells (BMMSC), skeletal muscle cells (SMC), and co
      culture of both types of cells (CO). Forty-four adult Wistar male rats (250-300g)
      received cultured cells CO (n = 22), BMMSC (n = 10), and SMC (n = 12). All
      cultured cells were started with the same concentration: 5 x 10(5)/mL, under
      similar conditions and maintained in an incubator with 5% CO(2) at 37 degrees C,
      which was changed every 48 hours for 14 days. The cell count was performed in
      Neubauer's chamber to calculate the proliferation index (IP). Statistical
      analysis was performed by the nonparametric Kruskal-Wallis and Wilcoxon tests. P
      values <.05 were considered statistically significant. The results showed that IP
      was positive in all groups. In conclusion, proliferation capacity was
      demonstrated in all groups. SMC IP was greater than the others, although it was
      the most heterogeneous.

PMID- 16908335
TI  - Patient-reported outcomes in overactive bladder: importance for determining
      clinical effectiveness of treatment.
AB  - Overactive bladder (OAB) is a condition defined by its symptoms--urinary urgency
      with or without urgency urinary incontinence and often with frequency and
      nocturia. As such, determining the efficacy of OAB treatments using objective
      measures, such as urodynamic testing, can be difficult. A better means of gauging
      treatment efficacy for symptom-based conditions is through the use of patient
      reported outcomes (PROs). With PROs, clinicians can gain insight into how a
      treatment affects a patient's symptoms and whether improvement in symptoms has a
      positive effect from the patient's perspective. PROs are increasingly being
      included as end points in clinical trials, including those of antimuscarinic
      drugs for OAB. Consequently, clinicians should become familiar with the most
      commonly used instruments. We provide an overview of instruments used to assess
      symptoms, health-related quality of life, and treatment satisfaction in patients
      with OAB and discuss how PROs can be incorporated into clinical trial protocols.

PMID- 16908336
TI  - Development and validation of patient-reported outcomes measures for overactive
      bladder: a review of concepts.
AB  - Patient-reported outcome (PRO) measures are a valuable means for determining how
      a disease and its treatment affect patients, including effects on health-related
      quality of life (HRQL). To ensure that the results obtained with PROs are
      clinically useful, data must be gathered using valid and reliable instruments.
      Developing such instruments requires a multistep, structured process that
      incorporates cognitive psychology, psychometric theory, and patient and clinician
      input. The process begins by determining the intent and purpose of the PRO and
      culminates in studies that demonstrate the measure's validity, reliability, and
      responsiveness. Several valid and reliable PROs are available for assessing the
      effects of treatment on symptom severity, symptom bother, and HRQL in patients
      with overactive bladder.

PMID- 16908337
TI  - Assessment of treatment outcomes in patients with overactive bladder: importance
      of objective and subjective measures.
AB  - Overactive bladder (OAB) is a highly prevalent symptom syndrome that negatively
      affects health-related quality of life (HRQL). In clinical practice, the
      diagnosis and treatment of OAB are largely driven by a patient's reporting of
      symptoms, often in combination with objective assessment. Thus, OAB provides the
      opportunity to examine the relations between objective (eg, urodynamic studies,
      bladder diary variables) and subjective (eg, symptom bother, HRQL) outcomes. We
      compared objective and subjective results from 27 trials recently evaluated in a
      systematic review and meta-analysis of antimuscarinic agents used to treat OAB.
      Many studies demonstrated concurrent improvements in both types of outcomes.
      However, several reports showed that although pharmacotherapy may reduce
      micturition frequency or increase bladder capacity, treated patients may not
      perceive a significant benefit to HRQL. We conclude that objective assessments
      can help determine the underlying causes of OAB symptoms and assess the effects
      of treatment, but that these results are not always predictive of subjective
      outcomes, which are influenced by a patient's priorities and lifestyle, and thus
      highly individualized. A patient's perception of treatment success should be
      regarded as an important measure of efficacy because a patient considers the
      trade-offs between symptom improvement, adverse events, and effects on daily life
      when assessing overall treatment benefit. We recommend that subjective measures
      become standard considerations in the initial evaluation and treatment of
      patients with OAB.

PMID- 16908338
TI  - Patient-reported outcomes in overactive bladder: the influence of perception of
      condition and expectation for treatment benefit.
AB  - Patient perceptions of overactive bladder (OAB) symptoms, expectations for
      treatment benefit, and overall treatment satisfaction share complex relations.
      Multiple studies have demonstrated associations between factors, such as age,
      sex, and ethnicity, and patient perceptions of OAB symptoms, especially urgency
      urinary incontinence. Perceptions of OAB are also shaped by symptom severity and
      impact on health-related quality of life, as well as by perceptions of family
      members, caregivers, and clinicians. The literature further suggests
      discrepancies in the reporting among patients, physicians, and family
      members/caregivers of the impact that urinary symptoms have on patients'
      emotional well-being, productivity, and daily life. Understanding the factors
      that affect patients' perceptions is important because these perceptions affect
      treatment expectations, which may predict treatment outcomes. Studies designed to
      evaluate the relations between expectations for OAB treatment and patient
      satisfaction have not been performed to date, but studies in other patient
      populations suggest that expectations of positive outcomes are associated with
      greater treatment satisfaction. We emphasize that patient satisfaction with
      treatment is directly related to fulfillment of positive expectations, and that
      patient expectations should be realistic and agreed on by patient and physician.
      We also discuss strategies that may be used by physicians managing patients with
      OAB to develop stronger patient-physician partnerships, including the effective
      communication required to make treatment decisions and set realistic
      expectations.

PMID- 16908339
TI  - The effects of antimuscarinics on health-related quality of life in overactive
      bladder: a systematic review and meta-analysis.
AB  - The objective of this study was to review the effects of antimuscarinic
      treatments on health-related quality of life (HRQL) in patients with overactive
      bladder (OAB). MEDLINE, EMBASE, the Cochrane Controlled Trials Register, and the
      Cumulative Index to Nursing and Allied Health Literature databases were searched
      from 1966 through August 2004 for randomized controlled trials of antimuscarinic
      agents. HRQL data from included trials were extracted, and meta-analysis was
      performed where possible. Of 56 trials included, 25 (45%) reported HRQL and/or
      patient-reported outcomes. The most commonly used instruments were the
      Incontinence Impact Questionnaire (3 trials), the King's Health Questionnaire
      (KHQ; 5 trials), the Medical Outcomes Study Short Form-36 (2 trials), the Gaudenz
      Appraisal Questionnaire (3 trials), and the Urogenital Distress Inventory (2
      trials). Results from the meta-analyses of placebo-controlled trials showed
      statistically significant differences in favor of antimuscarinic therapy.
      Differences in HRQL as assessed using the KHQ were also clinically meaningful.
      The meta-analysis results of active-controlled trials did not show significant
      differences among antimuscarinic agents. This review provides evidence that
      antimuscarinics provide an HRQL benefit to patients with OAB. HRQL outcomes using
      validated instruments are recommended for inclusion in active-controlled trials,
      and agreement on the most appropriate HRQL instrument is now required.

PMID- 16908340
TI  - The NRAMP family of metal-ion transporters.
AB  - The family of NRAMP metal ion transporters functions in diverse organisms from
      bacteria to human. NRAMP1 functions in metal transport across the phagosomal
      membrane of macrophages, and defective NRAMP1 causes sensitivity to several
      intracellular pathogens. DCT1 (NRAMP2) transport metal ions at the plasma
      membrane of cells of both the duodenum and in peripheral tissues, and defective
      DCT1 cause anemia. The driving force for the metal-ion transport is proton
      gradient (protonmotive force). In DCT1 the stoichiometry between metal ion and
      proton varied at different conditions due to a mechanistic proton slip. Though
      the metal ion transport by Smf1p, the yeast homolog of DCT1, is also a
      protonmotive force, a slippage of sodium ions was observed. The mechanism of the
      above phenomena could be explained by a combination between transporter and
      channel mechanisms.

PMID- 16908341
TI  - Azathioprine in dermatology: the past, the present, and the future.
AB  - For several decades, dermatologists have utilized azathioprine to treat numerous
      debilitating skin diseases. This synthetic purine analog is derived from 6
      mercaptopurine. It is thought to act by disrupting nucleic acid synthesis and has
      recently been found to interfere with T-cell activation. The most recognized uses
      of azathioprine in dermatology are for immunobullous diseases, generalized
      eczematous disorders, and photodermatoses. In this comprehensive review, the
      authors present recent advancements in the understanding of azathioprine and
      address aspects not covered in prior reviews. They (1) summarize the history of
      azathioprine; (2) discuss metabolism, integrating information from recent
      publications; (3) review the mechanism of action with attention paid to the
      activities of azathioprine not mediated by its 6-mercaptopurine metabolites and
      review new data about inhibition by azathioprine of the CD28 signal transduction
      pathway; (4) thoroughly examine thiopurine s-methyltransferase genetics, its
      clinical relevance, and interethnic variations; (5) review prior uses of
      azathioprine in the field of dermatology and grade the level of evidence; (6)
      discuss the use of azathioprine in pregnancy and pediatrics; review (7) key drug
      interactions and (8) adverse effects; (9) suggest a dosing and monitoring
      approach different from prior recommendations; and (10) explore the future of
      azathioprine, focusing on laboratory considerations and therapeutic application.

PMID- 16908342
TI  - Homozygosity mapping as a screening tool for the molecular diagnosis of
      hereditary skin diseases in consanguineous populations.
AB  - BACKGROUND: The routine diagnosis of genodermatoses is significantly complicated
      by the fact that in this group of disorders, clinical manifestations may result
      from mutations in unrelated genes (genetic heterogeneity) and mutations in the
      same gene often lead to dissimilar clinical signs (phenotypic heterogeneity).
      METHODS: In this study, we applied the principles of homozygosity mapping as a
      screening method before formal mutational analysis in an attempt to facilitate
      the molecular diagnosis of genodermatoses in consanguineous families. The method
      was evaluated in a retrospective fashion in 4 families previously assessed with
      junctional epidermolysis bullosa and in a prospective manner in 11 families with
      congenital recessive ichthyosis. RESULTS: The method was found to be efficient in
      directing the molecular analysis to one of the 4 genes commonly involved in the
      pathogenesis of junctional epidermolysis bullosa or in identifying cases of
      congenital recessive ichthyosis caused by mutations in TGM1. We found that this
      diagnostic strategy results in a 5-fold decrease in the cost of mutation
      analysis. LIMITATIONS: The proposed diagnostic strategy is applicable to
      consanguineous families only and, therefore, cannot be used in outbred
      populations. CONCLUSION: Our results indicate that homozygosity mapping may serve
      as a useful adjunct in the molecular diagnosis of junctional epidermolysis
      bullosa or congenital recessive ichthyosis in inbred populations. This study
      emphasizes the usefulness in human genetics of diagnostic strategies tailored to
      the demographic features of target populations.

PMID- 16908343
TI  - The effects of laser-mediated hair removal on immunohistochemical staining
      properties of hair follicles.
AB  - BACKGROUND: The mechanisms involved in laser-mediated hair removal remain
      unclear. One means of reducing hair growth is alteration of follicular stem
      cells. OBJECTIVE: We sought to examine the effects of laser hair removal on the
      immunohistochemical staining properties of human hair follicles, including the
      putative stem cells of the bulge region. METHODS: Treatment of unwanted axillary
      hair was performed on one side using an 800 nm-wavelength diode laser and on the
      other side using a 1064 nm-wavelength neodymium:yttrium-aluminum-garnet laser.
      Serial skin samples were obtained at baseline and various times after treatment
      and stained using immunohistochemical techniques. RESULTS: Hair shafts were
      thermally altered, but the immunostaining properties of much of the follicle,
      including the bulge region, remained generally unchanged. LIMITATIONS: This study
      only addressed the acute immunohistochemical changes found after a single
      treatment using specific laser parameters. CONCLUSIONS: Laser-mediated hair
      removal does not appear to work by frank destruction of follicular stem cells.
      Other mechanisms including functional alteration of these cells may underlie the
      clinical efficacy of the procedure.

PMID- 16908344
TI  - Optical coherence tomography for the characterization of basal cell carcinoma in
      vivo: a pilot study.
AB  - BACKGROUND: Optical coherence tomography combines principles of ultrasonography
      and optical interferometry to provide real-time cross-sectional images of
      subsurface microstructure of tissue in vivo. OBJECTIVE: The purpose of this pilot
      study was to define and characterize basal cell carcinoma by using optical
      coherence tomography. METHODS: Twenty-three patients with 49 lesions clinically
      suggestive of superficial basal cell carcinoma were recruited. Optical coherence
      tomography was used to characterize the features of the pearly papules in real
      time and in vivo. Shave biopsy and light microscopic images were compared with
      images from optical coherence tomography. RESULTS: Basal cell carcinoma was
      identified in 27 patients; all 27 had optical coherence tomographic images for
      comparison. Seven images were uninterpretable, probably because of technical
      problems. Of the remainder, 20 sites matched the histologic features seen on
      light microscopy, with excellent correlation between optical coherence
      tomographic images and histopathologic features of superficial, nodular,
      micronodular and infiltrative basal cell carcinomas. LIMITATIONS: This study was
      limited by the small number of patients examined. Also, as this study was not
      designed as an intent-to-diagnose study, the actual predictive value of optical
      coherence tomography technology remains unproven. CONCLUSIONS: Optical coherence
      tomography technology has potential for the diagnosis and histopathologic
      characterization of basal cell cancer. Additional studies to determine any
      practical role for optical coherence tomography are indicated.

PMID- 16908345
TI  - Tattoos and body piercings in the United States: a national data set.
AB  - BACKGROUND: Little is known about the prevalence and consequences of body art
      application. OBJECTIVE: Our aim was to provide US tattooing and body piercing
      prevalence, societal distribution, and medical and social consequence data.
      METHODS: Random digit dialing technology was used to obtain a national
      probability sample of 253 women and 247 men who were 18 to 50 years of age.
      RESULTS: Of our respondents, 24% had tattoos and 14% had body piercings.
      Tattooing was equally common in both sexes, but body piercing was more common
      among women. Other associations were a lack of religious affiliation, extended
      jail time, previous drinking, and recreational drug use. Local medical
      complications, including broken teeth, were present in one third of those with
      body piercings. The prevalence of jewelry allergy increased with the number of
      piercings. Of those with tattoos, 17% were considering removal but none had had a
      tattoo removed. LIMITATIONS: This was a self-reported data set with a 33%
      response rate. CONCLUSION: Tattooing and body piercing are associated with risk
      taking activities. Body piercing has a high incidence of medical complications.

PMID- 16908346
TI  - Commentary: Tattoos and body piercing.

PMID- 16908347
TI  - Clinical and histopathologic characteristics of nevus depigmentosus.
AB  - BACKGROUND: Nevus depigmentosus (ND) is known to be a rare congenital,
      nonprogressive disorder characterized by a hypopigmented lesion that remains
      stable over time. There have been only few studies of clinical and
      histopathologic characteristics of ND, and the etiopathogenesis is not fully
      established. OBJECTIVE: The purpose of this study was to investigate the clinical
      and histopathologic characteristics of ND. METHODS: A clinical survey was carried
      out with 60 patients given the diagnosis of ND. Punch biopsies (2 mm) from
      lesional and perilesional normal skin were performed. The sections were stained
      with hematoxylin-eosin, Fontana-Masson, antibodies to S-100 protein, MART-1,
      NKI/beteb, CD1a, CD3, CD20, and CD68. RESULTS: The lesions were usually present
      before the age of 3 years (68.3%), but some lesions appeared later in childhood
      (31.7%). In all, 27 patients (45%) had one lesion, but there were 14 patients
      (23.3%) who had more than 10 lesions. Fontana-Masson stain showed that the amount
      of melanin was significantly decreased in ND skin compared with perilesional
      normal skin. Melanocyte counts were significantly decreased in ND skin when
      stained with antibodies to GP-100 and MART-1. However, there were no significant
      differences in the number of melanocytes identified as S-100 protein-positive
      cells. There were no significant differences in histologic findings or dermal
      inflammatory infiltrates between ND skin and perilesional normal skin.
      LIMITATIONS: Only 29 patients (48.3%) were followed up, and the average follow-up
      period after initial diagnosis was relatively short (68 months); therefore, these
      overall results may not be representative of the clinical course of the patients.
      CONCLUSION: Only 18 patients (30.0%) presented with ND since birth and only 27
      patients (45.0%) had one lesion. Both the amount of melanin and the number of
      melanocytes in ND skin were decreased in patients with ND. Therefore, both
      clinical and histologic findings should be considered together to make a
      diagnosis of ND.

PMID- 16908349
TI  - Alopecia areata: a long term follow-up study of 191 patients.
AB  - BACKGROUND: The prognosis of alopecia areata (AA) is difficult to predict. Few
      studies report long-term follow-up of AA patients. OBJECTIVE: The purpose of this
      study is to better assess the long-term evolution of AA and the possible
      relationship between disease severity and treatment response with long-term
      prognosis. METHODS: One hundred ninety-one patients with AA who presented with a
      new diagnosis of AA between 1983 and 1990 were subsequently contacted by phone.
      Patients were queried regarding current disease status, treatments, and disease
      course. RESULTS: Severity of AA at first consultation ranged from mild (128
      patients) to severe (63 patients). Fifty-five of 191 patients were affected by
      concomitant autoimmune or related inflammatory disease. Sixty-six of 191 patients
      were presently disease free (follow-up duration, 15-22 years; mean 17.74 years).
      These include 41 of 60 patients with S1 disease (68.3%), 22 of 68 patients with
      S2 disease (32.3%), 1 of 11 patients with S3 disease (9%), 1 of 14 patients with
      S4 disease (7.1%), and 1 of 11 patients with alopecia totalis (AT) (9.1%). Sixty
      nine of 191 patients (36-1%) were presently affected by AT or alopecia
      universalis. There was a statistically significant tendency of severe patterns of
      AA to worsen over time. In children, 18 of 39 (13 with < or =S2 disease and 5
      with > or =S3 disease) with AA had developed AT or alopecia universalis at long
      term follow-up. In children, however, this trend was not statistically
      significant. Patients with severe AA who responded to topical immunotherapy seem
      to have a better prognosis than nonresponders. LIMITATIONS: Follow-up was only
      performed by phone. CONCLUSIONS: Severity of AA at time of first consultation is
      an important prognostic factor. Response to therapy (topical immunotherapy) may
      be associated with better prognosis. In children, the prognosis is worse; our
      study found that AA worsens over time.

PMID- 16908348
TI  - Description and management of cutaneous side effects during cetuximab or
      erlotinib treatments: a prospective study of 30 patients.
AB  - BACKGROUND: Drugs such as cetuximab or erlotinib, which inhibit the epidermal
      growth factor receptor, are increasingly being used in treatment of solid tumors.
      This has led to the appearance of new secondary effects. OBJECTIVE: We sought to
      describe the cutaneous side effects and their management in patients with cancer
      treated with cetuximab or erlotinib. METHODS: We clinically examined 30 patients
      determining type, frequency, treatment, and evolution of side effects. RESULTS:
      Most patients presented with a cutaneous reaction consisting of a follicular
      eruption, typically appearing in seborrheic areas within the first 15 days of
      treatment. Painful fissures in palms and soles and paronychia were the second
      most common cutaneous toxicities. We also noticed an alteration in hair growth at
      several months' follow-up. As these secondary effects responded well to
      treatment, few patients discontinued the antineoplastic therapy because of
      cutaneous toxicity. LIMITATIONS: This was a prospective but uncontrolled study.
      CONCLUSION: Although these new targeted therapies have low systemic toxicity
      because of their high specificity, cutaneous side effects are common and may be
      serious.

PMID- 16908350
TI  - A risk management program aimed at preventing fetal exposure to isotretinoin:
      retrospective cohort study.
AB  - BACKGROUND: Preventing fetal exposure to isotretinoin is an important public
      health goal. Since approval of isotretinoin (1982), the Food and Drug
      Administration has implemented several unsuccessful risk management programs
      aimed at preventing fetal exposure. The Kaiser Permanente isotretinoin risk
      management program included electronic capture of all isotretinoin prescriptions
      and the documentation of pregnancy testing with each dispense. OBJECTIVE: Our aim
      was to analyze the success of Kaiser Permanente's program at improving pregnancy
      testing rates and reducing fetal exposure. METHODS: This was a retrospective
      cohort study. RESULTS: Pregnancy testing rates improved after implementation of
      the Kaiser Permanente program. However, the rate of fetal exposure to
      isotretinoin did not change (0.21% before vs 0.23% after, P = .85).
      LIMITATIONS/CONCLUSION: In this study, linking a negative pregnancy test to
      isotretinoin dispensing did not reduce fetal exposures. Patient failure to use
      two contraceptive methods was the most common reason for fetal exposure. These
      results have important implications for iPLEDGE, the new isotretinoin risk
      management program mandated by the Food and Drug Administration.

PMID- 16908351
TI  - Rituximab: a monoclonal antibody to CD20 used in the treatment of pemphigus
      vulgaris.
AB  - BACKGROUND: Rituximab is an anti-CD20 chimeric antibody that selectively targets
      B lymphocytes. Recently, it has been reported to be beneficial in treating
      pemphigus vulgaris. OBJECTIVE: Our aim was to review the English-language
      literature on the treatment of pemphigus vulgaris (PV) with rituximab and to
      determine its efficacy and influence on clinical outcome(s). MATERIAL AND
      METHODS: A retrospective review of the literature on the use of rituximab in the
      treatment of PV was conducted. Seventeen patients in 10 reports were described
      and their data were reviewed. RESULTS: The majority of patients received one
      course of rituximab along with conventional immunosuppressive therapy as
      concomitant therapy; 88% of the patients demonstrated improvement. More than half
      of the patients were followed up for more than 6 months after rituximab
      treatment; they appeared to be clinically disease free, but were still receiving
      conventional immunosuppressive therapy. Side effects in most patients were
      transient and infusion related. Serious infections occurred in 4 patients. One
      patient died. LIMITATIONS: The sample size of this study is small; there is no
      uniformity of data collection or measurement of key and critical indices, and
      follow-up was limited. CONCLUSION: Rituximab may be a promising agent in
      treatment of PV.

PMID- 16908352
TI  - Is melanocytic nevus with focal atypical epithelioid components (clonal nevus) a
      superficial variant of deep penetrating nevus?
AB  - BACKGROUND: We compare features of two similar nevi which may be confused with
      melanoma: deep penetrating nevus (DPN), and nevus with focal atypical epithelioid
      component (NFAEC). METHODS: Clinical/demographic and histologic information
      regarding 146 DPN and 81 NFAEC were compared. Patient outcomes were ascertained
      via a questionnaire solicited to the referring physicians. RESULTS: Clinical
      features were similar for each type of nevus. Histologically, all lesions
      demonstrated identical aggregates of epithelioid melanocytes. DPN more often
      extended into the deep dermis or subcutaneous tissue, while NFAEC was typically
      confined to the superficial dermis. NFAEC more often demonstrated a junctional
      component (P < .001) and coexistent common nevus with congenital features (P =
      .035). DPN more often demonstrated adnexal spread (P < .001). A subgroup with
      overlapping features was identified. With an average of 6.4 years follow-up,
      there were just two recurrences, and no metastases. LIMITATIONS: This
      retrospective study utilized tissue specimens from a single reference laboratory;
      ergo, some inherent selection bias exists. Specimens were randomly selected for
      P53 immunostaining, leading also to potential sampling error. CONCLUSIONS: DPN
      and NFAEC show considerable similarity, differing mainly in the depth of extent
      for the lesion. It is possible that NFAEC represents a more superficial variant
      of DPN. A subgroup with overlapping features, but intermediate depth, supports
      such a relationship.

PMID- 16908353
TI  - T-cell prolymphocytic leukemia: an aggressive T cell malignancy with frequent
      cutaneous tropism.
AB  - BACKGROUND: T-cell prolymphocytic leukemia (T-PLL), formerly categorized as T
      cell chronic lymphocytic leukemia, is a rare and aggressive hematologic
      malignancy. Although the skin is characteristically involved, it is not a well
      recognized entity in the dermatologic literature. METHODS: Six cases of cutaneous
      T-PLL are presented from a clinical, light microscopic, and phenotypic
      perspective. RESULTS: The patient population comprised 2 women and 4 men, with a
      mean age of 69.8 years. The disease was associated in all with skin involvement
      with facial preference; edema, purpura, and lesional symmetry were
      characteristic. The skin biopsies demonstrated a largely non-epidermotropic
      angiocentric lymphocytic infiltrate with accompanying hemorrhage. The cells
      showed irregular- to reniform-shaped nuclei with small nucleoli and eosinophilic
      rims of cytoplasm. Phenotypic studies revealed three prevailing profiles: CD4
      dominant in 4, CD8 dominant in one, and co-expression of CD4 and CD8 in one. CD3
      loss was seen in one case. All expressed T-cell leukemia 1 (TCL-1) and CD7;
      cutaneous lymphocyte antigen expression was discernible in a dot-like perinuclear
      array. All cases tested excluding one expressed TCL-1 and CD52. In two cases
      tested, T-cell receptor beta rearrangements were observed. Cytogenetic studies
      demonstrated a paracentromeric chromosome 14 inversion. Polysomy 8 and MYC
      amplification was seen in one case, manifesting an aggressive clinical course.
      Four patients died from their disease within 18 months of diagnosis. LIMITATIONS:
      Cytogenetic MYC amplification, FISH, and TCR beta studies were conducted on each
      of 2 cases, respectively, due to limitations of tissue block samples and/or
      peripheral blood. cMYC translocation studies were conducted on 3 of the 6 cases,
      again due to limitations imposed by the tissue samples on the cases. The last
      case was recently diagnosed and, therefore, long-term follow-up is not possible.
      CONCLUSION: T-PLL is a distinctive post-thymic T-cell malignancy with frequent
      cutaneous tropism. A diagnosis is possible in almost all cases based on
      characteristic clinical, light microscopic, phenotypic, and cytogenetic features.
      While a chromosome 14 inversion is highly characteristic, additional inherent
      cytogenetic differences, such as trisomy 8 with CMYC over-amplification, may
      account for some case to case variation in clinical course.

PMID- 16908354
TI  - Monkeypox: an epidemiologic and clinical comparison of African and US disease.
AB  - Monkeypox is a double-stranded DNA virus and a member of the genus Orthopoxvirus.
      Human monkeypox was first identified in the Democratic Republic of the Congo
      (formerly Zaire) in 1970. The first outbreak in the western hemisphere occurred
      in the spring of 2003. Important epidemiologic and clinical differences exist
      between human monkeypox in the United States and in Africa, including sex
      distribution, case fatality, morphology of skin lesions, and associated
      lymphadenopathy. These divergent clinical presentations could be caused by mode
      of transmission (skin inoculation vs ingestion), the skin color of affected
      patients, the training backgrounds of those who saw and documented disease
      outbreaks, the virulence of monkeypox strains involved, nutritional status,
      access to advanced medical care, and the prevalence of prior smallpox
      vaccinations.

PMID- 16908355
TI  - Adverse events associated with nonablative cutaneous visible and infrared laser
      treatment.
AB  - Since the theory of selective thermolysis was developed in the early 1980s, there
      have been numerous advances in both laser technology and the understanding of
      laser-tissue interaction. Nonablative dermatologic treatments involving laser
      light continue to be increasingly used for a number of diverse applications such
      as skin remodeling, the treatment of cutaneous melanocytic and vascular lesions,
      and the removal of undesired hair and tattoo pigment. Although these techniques
      are regarded as safe, both temporary and permanent adverse reactions do occur,
      many of which are thermally mediated. Little has been published on the frequency
      of adverse events in nonablative cutaneous laser treatments, or on the
      comparative efficacy of the various strategies commonly used to minimize them.
      Through reviewing relevant publications from the last 5 years, this article will
      address both these issues.

PMID- 16908356
TI  - The burden of skin diseases: 2004 a joint project of the American Academy of
      Dermatology Association and the Society for Investigative Dermatology.
AB  - Skin disease is one of the top 15 groups of medical conditions for which
      prevalence and health care spending increased the most between 1987 and 2000,
      with approximately 1 of 3 people in the United States with a skin disease at any
      given time. Even so, a national data profile on skin disease has not been
      conducted since the late 1970s. This study closes the gap by estimating the
      prevalence, economic burden, and impact on quality of life for 22 leading
      categories of skin disease. The estimated annual cost of skin disease in 2004 was
      39.3 billion dollars, including 29.1 billion dollars in direct medical costs
      (costs of health services and products) and 10.2 billion dollars in lost
      productivity costs (defined as costs related to consumption of medical care,
      costs associated with impaired ability to work, and lost future earning potential
      because of premature death). Based on a methodology of willingness to pay for
      symptom relief, the additional economic burden of skin disease on quality of life
      amounted to an estimated 56.2 billion dollars. Including the economic burden on
      quality of life, the total economic burden of skin disease to the US public in
      2004 was approximately 96 billion dollars.

PMID- 16908357
TI  - Sildenafil for the treatment of Raynaud's phenomenon.

PMID- 16908358
TI  - UV light exposure counseling and reality.

PMID- 16908359
TI  - The benefits of skin cancer prevention counseling for parents and children.

PMID- 16908360
TI  - Surgical Pearl: Removal of large oval lesions with a smaller round punch.

PMID- 16908361
TI  - Surgical Pearl: The use of a laboratory vortex for poly-L-lactic acid injection.

PMID- 16908362
TI  - Surgical Pearl: Dermoscopy of the free edge of the nail to determine the level of
      nail plate pigmentation and the location of its probable origin in the proximal
      or distal nail matrix.

PMID- 16908363
TI  - Surgical Pearl: A rapid and effective technique for perioperative hair removal.

PMID- 16908364
TI  - Surgical Pearl: The use of petroleum jelly in performing scalp surgery.

PMID- 16908365
TI  - Etanercept for the treatment of psoriasis in the elderly.
AB  - This study's objective was to analyze the effect of etanercept on Psoriasis Area
      and Severity Index (PASI) 50, PASI 75, and Dermatology Life Quality Index in
      geriatric and nongeriatric populations. We conducted a post hoc analysis of two
      large phase III randomized placebo trials of etanercept. There were no
      statistically significant differences between the elderly and young with regard
      to the number of patients reaching a PASI 50 or PASI 75 at any of the 3 dosing
      regimens. Baseline Dermatology Life Quality Index scores were not statistically
      significant between both groups and both the elderly and young had similar
      changes in Dermatology Life Quality Index with therapy. A limitation of the study
      was the small number of patients in the elderly group. In conclusion, psoriasis
      and its treatment has a similar impact on quality of life in the elderly as it
      does in the young.

PMID- 16908366
TI  - Histopathologic findings in primary erythromelalgia are nonspecific: special
      studies show a decrease in small nerve fiber density.
AB  - The histopathology of primary erythromelalgia has been poorly characterized. A
      total of 33 skin biopsy specimens from 29 patients with a diagnosis of primary
      erythromelalgia were re-examined. Histopathologic findings were nonspecific.
      Vascular thrombi were not identified. A relative decrease in small nerve fiber
      density was noted in specimens from 13 of 16 patients.

PMID- 16908367
TI  - Educational conferences in dermatology residency programs.
AB  - To characterize conferences in dermatology residency programs, we surveyed
      directors and chief residents. Most respondents thought their amount of
      conference time was just right (7-8 hours/wk); they also identified grand rounds,
      dermatopathology, and clinical images as best implemented, whereas journal club
      and basic science needed most improvement. By contrast, respondents diverged
      regarding conferences they wanted to establish; directors identified research and
      basic science, whereas chief residents listed pediatrics and surgery.

PMID- 16908369
TI  - Treatment of alopecia areata partim universalis with efalizumab.
AB  - Alopecia areata (AA) is considered an autoimmune disease targeted at hair
      follicles with T-lymphocytes playing an important role in the pathogenesis.
      Treatment of AA, particularly the totalis and universalis subtypes, is often
      difficult and remains a therapeutic challenge. Novel biologic therapies that have
      been developed for the treatment of other immune-mediated inflammatory skin
      diseases may represent a new therapeutic modality for this disease. Efalizumab is
      a humanized monoclonal anti-CD11a antibody that inhibits T-cell activation and
      migration. We report a case of a 19-year-old man suffering from AA partim
      universalis, treated with efalizumab monotherapy. The treatment was well
      tolerated with no reported side effects. The striking improvement warrants
      further studies with this biologic therapy in AA.

PMID- 16908368
TI  - Acute generalized exanthematous pustulosis following a spider bite: report of 3
      cases.
AB  - Acute generalized exanthematous pustulosis (AGEP) is a rare severe cutaneous
      adverse reaction caused mostly by drugs. Three of 22 AGEP cases (13.6%),
      recruited by us as part of two prospective multinational studies, occurred 24 to
      48 hours after a spider bite. We suggest that a spider bite is a possible trigger
      for AGEP.

PMID- 16908370
TI  - Intravenous cidofovir-induced resolution of disfiguring cutaneous human
      papillomavirus infection.
AB  - Human papillomavirus infection is one of the most common and most distressing
      cutaneous diseases in patients with HIV infection. It is also a common, and often
      therapeutically challenging, infection in individuals who are immunologically
      competent. A wide range of therapeutic options exists for treating cutaneous
      human papillomavirus infections, but none is uniformly effective. In this report
      we describe a man with HIV-1 infection and disfiguring facial verruca vulgaris
      who demonstrated complete clinical response to intravenous cidofovir. Our report
      provides further support for the use of intravenous cidofovir as therapy for
      treatment-resistant and/or widespread cutaneous human papillomavirus infection.

PMID- 16908371
TI  - Imiquimod for the treatment of actinic keratosis: A meta-analysis of randomized
      controlled trials.

PMID- 16908372
TI  - Dictation templates improve coding accuracy in an academic dermatology practice.

PMID- 16908373
TI  - Wanted: A study with omalizumab to determine the role of IgE-mediated pathways in
      atopic dermatitis.

PMID- 16908375
TI  - Academic?

PMID- 16908377
TI  - Mirtazapine and gabapentin for reducing pruritus in cutaneous T-cell lymphoma.

PMID- 16908378
TI  - Positive predictive value of skin cancer screening.

PMID- 16908381
TI  - Analysis of the upper face and selection of rejuvenation techniques.

PMID- 16908382
TI  - Upper face-lifting.

PMID- 16908383
TI  - Rejuvenation of the aging forehead.

PMID- 16908384
TI  - Subgaleal endoscopic browlift with absorbable fixation.

PMID- 16908385
TI  - Trichophytic endoscopic forehead-lifting in high hairline patients.

PMID- 16908386
TI  - The endoscopic forehead-lift.

PMID- 16908387
TI  - Endoscopic brow-lift with deep temporal fixation only (DTFO).

PMID- 16908388
TI  - Management of the midface.

PMID- 16908389
TI  - Lipocontouring in conjunction with the minimal incision brow and subperiosteal
      midface lift: the next dimension in midface rejuvenation.

PMID- 16908390
TI  - Autologous fat grafting for midface rejuvenation.

PMID- 16908391
TI  - Botulinum neurotoxins and injectable fillers: minimally invasive management of
      the aging upper face.

PMID- 16908392
TI  - Combining techniques to optimize upper facial rejuvenation.

PMID- 16908393
TI  - The use of botulinum toxin type A in the upper face.

PMID- 16908395
TI  - Community-acquired methicillin resistant Staphylococcus aureus skin infection.
AB  - Staphylococcus aureus is one of the most common pathogens in skin and soft tissue
      infections, as well as in potentially serious nosocomial infections in patients
      who acquire it when hospitalized. Penicillin was introduced in the 1940's as an
      effective treatment against S. aureus. However, shortly after penicillin's
      introduction, penicillin resistance to S. aureus emerged due to a plasmid
      mediated beta-lactamase enzyme. In 1959, a semisynthetic penicillin, methicillin
      was introduced to overcome the resistance problem. However, within a year,
      bacteria resistant to methicillin and other penicillinase stable beta-lactams,
      were present. Worldwide emergence of methicillin-resistant S aureus (MRSA) was
      established by the 1980's. Since that time, MRSA has become widespread in
      hospitals and long-term care facilities around the world, accounting for numerous
      nosocomial infections. Recently, there has been an alarming increase in the
      incidence of community-acquired MRSA (CA-MRSA). Patients with CA-MRSA began to be
      reported in the early 1990's and its prevalence has continued to increase. This
      paper summarizes the current information known about CA-MRSA as it relates to
      skin infections including populations at risk, clinical presentation, and
      treatment options.

PMID- 16908397
TI  - New clinical syndromes in dermatology.
AB  - Dermatologists are in the unique position to be able to diagnose serious systemic
      diseases through skin findings; in addition, cutaneous manifestations can be
      associated with internal symptoms and clarify the pathogenesis and treatment of
      challenging new syndromes. Calciphylaxix, now renamed Calcific Uremic
      Arteriolopathy, primarily affects patients with end-stage renal disease with
      concomitant hyperphosphatemia, increased calcium-phosphate product and
      hyperparathyroidism, skin biopsy and wound care are crucial parts of the
      diagnosis and treatment. Hyperhomocysteinemia may play a very important role in
      many cutaneous and systemic diseases including, chronic cutaneous wounds,
      systemic lupus erythematosus, Behcet's disease and psoriasis. Through a skin
      biopsy and biochemical analysis of the proteoglycans accumulation it may be
      possible to diagnose a new systemic mucinosis and prevent sudden death in
      patients with severe mitral valve prolapse. Nephrogenic Fibrosing Dermopathy is a
      newly described fibrosing disorder occurring in patients with end stage renal
      disease, the etiology and pathogenesis are still unknown, and the ultimate course
      of this disease has not been defined.

PMID- 16908396
TI  - What is new in the treatment of steroid-induced osteoporosis?
AB  - Glucocorticoid-induced osteoporosis (GIOP) is a serious complication resulting
      from long-term steroid treatment. In addition to several nonpharmacologic
      therapies recommended by the American College of Rheumatology, various
      pharmacologic therapies, such as calcium, vitamin D, hormone-replacement therapy,
      calcitonin, and bisphosphonates, can be used to prevent and/or treat GIOP.
      Bisphosphonates, which are potent inhibitors of bone resorption, are considered
      the most effective and first-line agents for increasing bone mineral density and
      decreasing the risk of fracture. Human parathyroid hormone has emerged as a
      promising agent for the treatment of severe GIOP when used alone or in
      combination with a bisphosphonate.

PMID- 16908398
TI  - What's new in cutaneous T-cell lymphomas: 2006.

PMID- 16908399
TI  - Toxic epidermal necrolysis and intravenous immunoglobulin: a review.
AB  - Toxic epidermal necrolysis (TEN, Lyell's syndrome) is a rare, life-threatening
      hypersensitivity reaction to certain medications, such as sulfonamides,
      antibiotics, non-steroidal anti-inflammatory drugs, and anti-convulsants. The
      incidence of TEN is 0.4-1.2 cases per million per year in the general population
      and 1 case per thousand per year in the HIV+ population. It is characterized
      morphologically by ongoing apoptotic keratinocyte cell death that results in the
      separation of the epidermis from the dermis. TEN carries a mortality of upwards
      of 40%, with the vast majority of patients succumbing to sepsis or multiorgan
      failure. Recent insights into the pathogenesis of TEN revealed that keratinocytes
      undergo Fas-FasL mediated apoptosis. No specific treatment for TEN exists to
      date. Attempts have been made to decrease mortality in TEN patients through
      supportive care and adjuvant therapies. Since 1988, intravenous immunoglobulin
      (IVIG) has been shown to interfere with the interaction of Fas and FasL, and can
      be used as a treatment for TEN. This paper reviews the recent studies in the
      literature that have looked at the use of IVIG to treat TEN.

PMID- 16908400
TI  - Infectious disease update: new anti-microbials.
AB  - Effective antimicrobials are critical in controlling one of the most common
      conditions encountered in medicine, namely, skin and skin structure infections.
      Unfortunately, the identification of appropriate and novel antimicrobials is
      continually challenged by the emergence of antimicrobial resistance among
      bacteria, fungi, and parasites. This work will focus on describing novel
      antibacterials and antifungals approved by the United States Food and Drug
      Administration in the past 4 years.

PMID- 16908401
TI  - Lichen myxedematosus (papular mucinosis): new concepts and perspectives for an
      old disease.
AB  - Lichen myxedematosus (LM) is an idiopathic cutaneous mucinosis; its
      classification dates back to 1953, when Montgomery and Underwood distinguished 4
      types of LM. In the literature, the terms LM, papular mucinosis, and
      scleromyxedema often have been used indiscriminately as synonyms, but most
      reported cases of LM or papular mucinosis without indication of the subtype
      appear in fact to be cases of scleromyxedema. Actually, LM includes 2
      clinicopathologic subsets: a generalized papular and sclerodermoid form (the only
      one which should be called scleromyxedema) with systemic, even lethal,
      manifestations and a localized form, which does not run a disabling course. The
      localized form is subdivided into 4 subtypes: (1) a discrete papular form
      involving any site; (2) acral persistent papular mucinosis involving only the
      extensor surface of the hands and wrists; (3) papular mucinosis of infancy, a
      pediatric variant of the discrete form or the acral form of persistent papular
      mucinosis; and (4) nodular form. A third group of atypical or intermediate forms,
      not meeting the criteria for either scleromyxedema or the localized form,
      includes cases of (1) scleromyxedema without monoclonal gammopathy, (2) localized
      forms with monoclonal gammopathy and/or systemic symptoms, (3) localized forms
      with mixed features of the subtypes, and (4) not well-specified cases.

PMID- 16908402
TI  - Contact dermatitis and workforce economics.
AB  - The roots of education in patch testing begin with Jadassohn and have been passed
      down through generations of dermatologists through didactic teachings and
      mentoring. Currently, we are faced with workforce economics tipping the balance
      of dermatology toward cosmetic and surgical practices. This imbalance is easily
      found in the subspecialty of contact dermatitis, where the current demand for
      patch test services is on the rise and the number of new dermatology-based patch
      test providers cannot keep up with the current demand. Steps are being made to
      remedy this discrepancy through societies and fellowships, yet the question
      remains: were the steps in time and were they big enough?

PMID- 16908403
TI  - RGS expression level precisely regulates the duration of rod photoresponses.
AB  - Regulators of G protein signaling (RGS) constitute a family of proteins that bind
      specifically to the activated alpha subunits of G proteins (Galpha-GTP), acting
      as GTPase activating proteins, or GAPs, for the rate of GTP hydrolysis. In this
      issue of Neuron, Krispel et al. resolve a long-standing puzzle in
      phototransduction, establishing that RGS9 "GAPping" of G(t)alpha-GTP is the
      molecular mechanism underlying the dominant recovery time constant of mouse rod
      photoreceptors and that a precise level of expression of RGS9 is required for
      normal photoresponse timing.

PMID- 16908404
TI  - Not too excited? Thank your endocannabinoids.
AB  - Endocannabinoids can mediate neuroprotection, but it is not known how. In this
      issue of Neuron, Monory et al. use mutant mice and localized viral targeting to
      produce conditional knockouts of the cannabinoid CB1 receptor. They show that
      protection against kainic acid-induced seizures and cell death is conferred by
      CB1Rs on hippocampal glutamatergic nerve terminals.

PMID- 16908405
TI  - The rodent orbitofrontal cortex gets time and direction.
AB  - The orbitofrontal cortex (OFC) helps direct decision making through its flexible
      coding of reward and economic value. In this issue of Neuron, papers by Roesch et
      al. and Feierstein et al. demonstrate the importance of temporal and spatial
      features to processing in the rodent OFC.

PMID- 16908406
TI  - Whole-cell recordings in freely moving rats.
AB  - Intracellular recording, which allows direct measurement of the membrane
      potential and currents of individual neurons, requires a very mechanically stable
      preparation and has thus been limited to in vitro and head-immobilized in vivo
      experiments. This restriction constitutes a major obstacle for linking cellular
      and synaptic physiology with animal behavior. To overcome this limitation we have
      developed a method for performing whole-cell recordings in freely moving rats. We
      constructed a miniature head-mountable recording device, with mechanical
      stabilization achieved by anchoring the recording pipette rigidly in place after
      the whole-cell configuration is established. We obtain long-duration recordings
      (mean of approximately 20 min, maximum 60 min) in freely moving animals that are
      remarkably insensitive to mechanical disturbances, then reconstruct the anatomy
      of the recorded cells. This head-anchored whole-cell recording technique will
      enable a wide range of new studies involving detailed measurement and
      manipulation of the physiological properties of identified cells during natural
      behaviors.

PMID- 16908407
TI  - RGS expression rate-limits recovery of rod photoresponses.
AB  - Signaling through G protein-coupled receptors (GPCRs) underlies many cellular
      processes, yet it is not known which molecules determine the duration of
      signaling in intact cells. Two candidates are G protein-coupled receptor kinases
      (GRKs) and Regulators of G protein signaling (RGSs), deactivation enzymes for
      GPCRs and G proteins, respectively. Here we investigate whether GRK or RGS
      governs the overall rate of recovery of the light response in mammalian rod
      photoreceptors, a model system for studying GPCR signaling. We show that
      overexpression of rhodopsin kinase (GRK1) increases phosphorylation of the GPCR
      rhodopsin but has no effect on photoresponse recovery. In contrast,
      overexpression of the photoreceptor RGS complex (RGS9-1.Gbeta5L.R9AP)
      dramatically accelerates response recovery. Our results show that G protein
      deactivation is normally at least 2.5 times slower than rhodopsin deactivation,
      resolving a long-standing controversy concerning the mechanism underlying the
      recovery of rod visual transduction.

PMID- 16908408
TI  - Calmodulin kinase II interacts with the dopamine transporter C terminus to
      regulate amphetamine-induced reverse transport.
AB  - Efflux of dopamine through the dopamine transporter (DAT) is critical for the
      psychostimulatory properties of amphetamines, but the underlying mechanism is
      unclear. Here we show that Ca(2+)/calmodulin-dependent protein kinase II (CaMKII)
      plays a key role in this efflux. CaMKIIalpha bound to the distal C terminus of
      DAT and colocalized with DAT in dopaminergic neurons. CaMKIIalpha stimulated
      dopamine efflux via DAT in response to amphetamine in heterologous cells and in
      dopaminergic neurons. CaMKIIalpha phosphorylated serines in the distal N terminus
      of DAT in vitro, and mutation of these serines eliminated the stimulatory effects
      of CaMKIIalpha. A mutation of the DAT C terminus impairing CaMKIIalpha binding
      also impaired amphetamine-induced dopamine efflux. An in vivo role for CaMKII was
      supported by chronoamperometry measurements showing reduced amphetamine-induced
      dopamine efflux in response to the CaMKII inhibitor KN93. Our data suggest that
      CaMKIIalpha binding to the DAT C terminus facilitates phosphorylation of the DAT
      N terminus and mediates amphetamine-induced dopamine efflux.

PMID- 16908409
TI  - NMDA receptor-nitric oxide transmission mediates neuronal iron homeostasis via
      the GTPase Dexras1.
AB  - Dexras1 is a 30 kDa G protein in the Ras subfamily whose discovery was based on
      its pronounced inducibility by the glucocorticoid dexamethasone. It binds to
      neuronal nitric oxide synthase (nNOS) via the adaptor protein CAPON, eliciting S
      nitrosylation and activation of Dexras1. We report that Dexras1 binds to the
      peripheral benzodiazepine receptor-associated protein (PAP7), a protein of
      unknown function that binds to cyclic AMP-dependent protein kinase and the
      peripheral benzodiazepine receptor. PAP7 in turn binds to the divalent metal
      transporter (DMT1), an iron import channel. We have identified a signaling
      cascade in neurons whereby stimulation of NMDA receptors activates nNOS, leading
      to S-nitrosylation and activation of Dexras1, which, via PAP7 and DMT1,
      physiologically induces iron uptake. As selective iron chelation prevents NMDA
      neurotoxicity in cortical cultures, the NMDA-NO-Dexras1-PAP7-DMT1-iron uptake
      signaling cascade also appears to mediate NMDA neurotoxicity.

PMID- 16908410
TI  - Dynamic translational and proteasomal regulation of fragile X mental retardation
      protein controls mGluR-dependent long-term depression.
AB  - Genetic deletion of fragile X mental retardation protein (FMRP) has been shown to
      enhance mGluR-dependent long-term depression (LTD). Herein, we demonstrate that
      mGluR-LTD induces a transient, translation-dependent increase in FMRP that is
      rapidly degraded by the ubiquitin-proteasome pathway. Moreover, proteasome
      inhibitors abolished mGluR-LTD, and LTD was absent in mice that overexpress human
      FMRP. Neither translation nor proteasome inhibitors blocked the augmentation of
      mGluR-LTD in FMRP-deficient mice. In addition, mGluR-LTD is associated with rapid
      increases in the protein levels of FMRP target mRNAs in wild-type mice.
      Interestingly, the basal levels of these proteins were elevated and their
      synthesis was improperly regulated during mGluR-LTD in FMRP-deficient mice. Our
      findings indicate that hippocampal mGluR-LTD requires the rapid synthesis and
      degradation of FMRP and that mGluR-LTD triggers the synthesis of FMRP binding
      mRNAs. These findings indicate that the translation, ubiquitination, and
      proteolysis of FMRP functions as a dynamic regulatory system for controlling
      synaptic plasticity.

PMID- 16908412
TI  - Encoding and decoding of overlapping odor sequences.
AB  - Odors evoke complex responses in locust antennal lobe projection neurons (PNs)
      the mitral cell analogs. These patterns evolve over hundreds of milliseconds and
      contain information about odor identity and concentration. In nature, animals
      often encounter many odorants in short temporal succession. We explored the
      effects of such conditions by presenting two different odors with variable
      intervening delays. PN ensemble representations tracked stimulus changes and, in
      some delay conditions, reached states that corresponded neither to the
      representation of either odor alone nor to the static mixture of the two. We then
      recorded from Kenyon cells (KCs), the PNs' targets. Their responses were
      consistent with the PN population's behavior: in some conditions, KCs were
      recruited that did not fire during single-odor or mixture stimuli. Thus, PN
      population dynamics are history dependent, and responses of individual KCs are
      consistent with piecewise temporal decoding of PN output over large sections of
      the PN population.

PMID- 16908411
TI  - The endocannabinoid system controls key epileptogenic circuits in the
      hippocampus.
AB  - Balanced control of neuronal activity is central in maintaining function and
      viability of neuronal circuits. The endocannabinoid system tightly controls
      neuronal excitability. Here, we show that endocannabinoids directly target
      hippocampal glutamatergic neurons to provide protection against acute
      epileptiform seizures in mice. Functional CB1 cannabinoid receptors are present
      on glutamatergic terminals of the hippocampal formation, colocalizing with
      vesicular glutamate transporter 1 (VGluT1). Conditional deletion of the CB1 gene
      either in cortical glutamatergic neurons or in forebrain GABAergic neurons, as
      well as virally induced deletion of the CB1 gene in the hippocampus, demonstrate
      that the presence of CB1 receptors in glutamatergic hippocampal neurons is both
      necessary and sufficient to provide substantial endogenous protection against
      kainic acid (KA)-induced seizures. The direct endocannabinoid-mediated control of
      hippocampal glutamatergic neurotransmission may constitute a promising
      therapeutic target for the treatment of disorders associated with excessive
      excitatory neuronal activity.

PMID- 16908413
TI  - Neural ensemble coding of satiety states.
AB  - The motivation to start or terminate a meal involves the continual updating of
      information on current body status by central gustatory and reward systems.
      Previous electrophysiological and neuroimaging investigations revealed region
      specific decreases in activity as the subject's state transitions from hunger to
      satiety. By implanting bundles of microelectrodes in the lateral hypothalamus,
      orbitofrontal cortex, insular cortex, and amygdala of hungry rats that
      voluntarily eat to satiety, we have measured the behavior of neuronal populations
      through the different phases of a complete feeding cycle (hunger-satiety-hunger).
      Our data show that while most satiety-sensitive units preferentially responded to
      a unique hunger phase within a cycle, neuronal populations integrated single-unit
      information in order to reflect the animal's motivational state across the entire
      cycle, with higher activity levels during the hunger phases. This distributed
      population code might constitute a neural mechanism underlying meal initiation
      under different metabolic states.

PMID- 16908414
TI  - Representation of spatial goals in rat orbitofrontal cortex.
AB  - The orbitofrontal cortex (OFC) is thought to participate in making and evaluating
      goal-directed decisions. In rodents, spatial navigation is a major mode of goal
      directed behavior, and anatomical and lesion studies implicate the OFC in spatial
      processing, but there is little direct evidence for coding of spatial or motor
      variables. Here, we recorded from ventrolateral and lateral OFC in an odor-cued
      two-alternative choice task requiring orientation and approach to spatial goal
      ports. In this context, over half of OFC neurons encoded choice direction or goal
      port location. A subset of neurons was jointly selective for the trial outcome
      and port location, information useful for the selection or evaluation of spatial
      goals. These observations show that the rodent OFC not only encodes information
      relating to general motivational significance, as shown previously, but also
      encodes spatiomotor variables needed to define specific behavioral goals and the
      locomotor actions required to attain them.

PMID- 16908416
TI  - Studies on the encapsulation of oxymatrine into liposomes by ethanol injection
      and pH gradient method.
AB  - Oxymatrine is the major active alkaloid constituent extracted from traditional
      Chinese herb medicine Sophora flavescens Ait (Kushen) and Sophora alopecuroides
      (Kudouzi). In recent years, oxymatrine had been found to posses remarkable anti
      hepatic activity and has been used for treating hepatitis B in clinical therapy
      in China. In this study, we attempted to entrap oxymatrine into liposomes to
      facilitate the delivery of oxymatrine to the liver and enhance the therapeutic
      efficiency for hepatitis. Preformulation investigation was performed to obtain
      the drug physicochemical properties such as solubility, pKa, and logP for
      rational liposomes preparation design. Liposomes were prepared with soybean
      lecithin by ethanol injection and pH gradient loading methods. At the same time
      the factors affecting the entrapment efficiencies were investigated and compared.
      Ethanol injection method yielded liposomes with entrapment efficiency less than
      20%. The lipid composition and aqueous medium had some effects on entrapment
      efficiency. However, liposomes could be produced with entrapment efficiency above
      50% by pH gradient method. The internal pH buffer capacity, the lipid
      composition, and drug-to-lipid ratio greatly influenced the entrapment
      efficiency, while the incubation temperature had almost no effect on entrapment
      efficiency in the active loading procedure.

PMID- 16908415
TI  - Encoding of time-discounted rewards in orbitofrontal cortex is independent of
      value representation.
AB  - We monitored single-neuron activity in the orbitofrontal cortex of rats
      performing a time-discounting task in which the spatial location of the reward
      predicted whether the delay preceding reward delivery would be short or long. We
      found that rewards delivered after a short delay elicited a stronger neuronal
      response than those delivered after a long delay in most neurons. Activity in
      these neurons was not influenced by reward size when delays were held constant.
      This was also true for a minority of neurons that exhibited sustained increases
      in firing in anticipation of delayed reward. Thus, encoding of time-discounted
      rewards in orbitofrontal cortex is independent of the encoding of absolute reward
      value. These results are contrary to the proposal that orbitofrontal neurons
      signal the value of delayed rewards in a common currency and instead suggest
      alternative proposals for the role this region plays in guiding responses for
      delayed versus immediate rewards.

PMID- 16908417
TI  - Development of rocket electrophoresis technique as an analytical tool in
      preformulation study of tetanus vaccine formulation.
AB  - Rocket Electrophoresis (RE) technique relies on the difference in charges of the
      antigen and antibodies at the selected pH. The present study involves
      optimization of RE run conditions for Tetanus Toxoid (TT). Agarose gel (1% w/v,
      20 ml, pH 8.6), anti-TT IgG - 1 IU/ml, temperature 4-8 degrees C and run duration
      of 18 h was found to be optimum. Height of the rocket-shaped precipitate was
      proportional to TT concentration. The RE method was found to be linear in the
      concentration range of 2.5 to 30 Lf/mL. The method was validated and found to be
      accurate, precise, and reproducible when analyzed statistically using student's t
      test. RE was used as an analytical method for analyzing TT content in plain and
      marketed formulations as well as for the preformulation study of vaccine
      formulation where formulation additives were tested for compatibility with TT.
      The optimized RE method has several advantages: it uses safe materials, is
      inexpensive, and easy to perform. RE results are less prone to operator's bias as
      compared to flocculation test and can be documented by taking photographs and
      scanned by densitometer; RE can be easily standardized for the required antigen
      concentration by changing antitoxin concentration. It can be used as a very
      effective tool for qualitative and quantitative analysis and in preformulation
      studies of antigens.

PMID- 16908418
TI  - Development of suspending agent from sodium carboxymethyl mungbean starches.
AB  - Three sodium carboxymethyl mungbean starches (SCMMSs) were selected, based on the
      physicochemical profiles and evaluated as potential pharmaceutical suspending
      agent in comparison with a sodium carboxymethyl tapioca starch and other five
      commercial suspending agents. Ibuprofen suspension was employed as a model
      formulation with 0.5, 1.0, and 2.0% w/v of suspending agents. Evaluation
      parameters included the determination of sedimentation volume ratio,
      redispersibility, viscosity and rheological properties and content uniformity
      studies. The results revealed that a high-viscosity modified mungbean starch, MMS
      M-04, possessed suitable properties as a suspending agent and, at 1%
      concentration, was as effective as sodium carboxymethylcellulose and xanthan gum,
      two most-commonly used suspending agents. This modified starch could be further
      developed and employed as a new commercial suspending agent in the pharmaceutical
      industry.

PMID- 16908419
TI  - Potential use of ascorbic acid-based surfactants as skin penetration enhancers.
AB  - 6-O-Ascorbic acid alkanoates (ASCn) are amphiphilic molecules having physical
      chemical properties that depend on the alkyl chain length. The derivatives of low
      molecular weight (n < 11) have enough aqueous solubility to produce self
      assemblies at room temperature ( approximately 25 degrees C), while those with
      longer alkyl chains possess a critical micellar temperature (CMT) higher than 30
      degrees C. At higher temperatures (T degrees > CMT), ASCn aqueous suspensions
      turn into either micellar solutions or gel phases, depending on the length of the
      hydrophobic chain. On cooling, coagels are produced, which possess a lamellar
      structure that exhibit sharp X-ray diffraction patterns and optical
      birefringence. The semisolid consistency of such coagels is an interesting
      property to formulate dermatological pharmaceutical dosage forms able to
      solubilize and stabilize different drugs. The objective of the present study was
      the evaluation of the enhancing permeation effect of ASCn with different chain
      lengths and to correlate permeability changes with histological effects. With
      this purpose, ASCn coagels containing anthralin (antipsoriasic drug) or
      fluorescein isothiocyanate (FITC, hydrophobic fluorescent marker) were assayed on
      rat skin (ex vivo) and mice skin (in vivo), respectively. Also, histological
      studies were performed aimed at detecting some possible side effects of ASCn. No
      inflammatory cellular response was observed in the skin when ASCn coagels were
      applied, suggesting non-irritating properties. Light microscopy indicated slight
      disruption and fragmentation of stratum corneum. The penetration of ASCn through
      rat skin epidermis was very fast and quantitatively significant. The permeation
      of anthralin was significantly increased when the drug was vehiculized in ASCn
      coagels, compared to other pharmaceutical systems. The results indicated that
      ASC12 seems to have the highest enhancing effect on FITC permeation. ASC12
      appears to be the compound that possesses the highest capacity to enhance the
      penetration of the drugs. Furthermore, it has the highest permeation of the
      serie.

PMID- 16908420
TI  - Evaluation and comparison of physicomechanical characteristics of gelatin and
      hypromellose capsules.
AB  - The aim of this study is evaluation and comparison of physical and mechanical
      properties of hypromellose and gelatin capsules. For this purpose, the empty and
      filled capsules of hypromellose and gelatin (size 4) were examined in regard with
      their physical and mechanical characteristics, employing textural analysis, and
      disintegration properties in various immersion fluids, utilizing a USP 28
      disintegration apparatus. The results demonstrated that owing to their greater
      water permeability, gelatin capsules disintegrate much faster than hypromellose
      shells in all tested media. However, hypromellose capsules showed a more uniform
      pattern of dispersion in the disintegration fluids. As for mechanical properties,
      at ambient conditions, gelatin capsules appeared to be harder and stronger with
      less elasticity as compared with hypromellose shells. On the contrary, at an
      elevated temperature, gelatin capsules demonstrated lower resilience. This study
      shows that hypromellose capsules have excellent properties and are promising as
      far as regulatory, manufacturing, religious, and dietary issues are concerned.

PMID- 16908421
TI  - Freeze-drying of composite core-shell nanoparticles.
AB  - The effects of four sugars (glucose, saccharose, maltose, trehalose) and one
      surfactant (Poloxamer 188), on the freeze-drying of poly(isobutylcyanoacrylate)
      (PIBCA), poly(epsilon-caprolactone)-poly(ethylene glycol) (PCL-PEG), and novel
      core (mainly PIBCA)-shell (principally PEG) composite nanoparticles (CNP)
      obtained by co-precipitation were investigated. The efficiency of the additives
      against the adverse effect of freeze-drying on the redispersibility of the
      nanoparticles was evaluated, based on the visual appearance of the nanoparticle
      suspensions (Tyndall effect and aggregation), and on the determination of the
      mean diameter ratio of the nanoparticles before and after freeze-drying. The
      results indicated that the addition of both sugars and surfactant was essential
      for the good redispersion of freeze-dried nanoparticles displaying hydrophobic
      (PIBCA) or hydrophilic (PCL-PEG and CNP) surfaces.

PMID- 16908422
TI  - Colonic drug delivery: influence of cross-linking agent on pectin beads
      properties and role of the shell capsule type.
AB  - For colonic delivery, pectin beads obtained by ionotropic gelation method have
      been already reported as an interesting approach. This study investigated the
      influence of the cross-linking agent (calcium or zinc) and the type of shell
      capsule used (classical or enteric capsules) on pectin beads properties and on
      their performance to target the colon (in vitro dissolution studies with
      subsequent pH change to mimic overall gastro-intestinal tract). Zinc pectinate
      beads seemed to be relatively similar to calcium's ones in morphological point,
      except on the surface aspect. When beads were introduced in classical hard
      capsules, ketoprofen release was not significantly different between CPG and ZPG
      beads, and it was too premature and too quick due to a chemical erosion of the
      pectinate matrix (acid + basic attacks). However, zinc pectinate beads showed
      slower ketoprofen release compared with calcium pectinate beads when enteric hard
      capsules were used. This interesting finding could be due to the strength of the
      network formed during the process between the zinc cations and the LM-pectin
      following the "egg-box" model. This network was stronger and induced a reduction
      of swelling and hydration when contact with dissolution medium, then subsequently
      a decrease of drug release. Thus, the zinc pectinate beads could protect
      sufficiently drug entrapped from the upper gastro-intestinal conditions and drug
      release will be controlled by pectin degradation with colonic microflora.
      Finally, these zinc pectinate beads in enteric hard capsules are promising as a
      carrier for specific colonic delivery of drugs after oral administration.

PMID- 16908423
TI  - Preparation of All-Trans Retinoic Acid nanosuspensions using a modified
      precipitation method.
AB  - All-Trans Retinoic Acid (ATRA) nanosuspensions were prepared with a modified
      precipitation method. The ATRA solution in acetone was injected into pure water
      by an air compressor under the action of ultrasonication. Photon correlation
      spectroscopy results showed that the mean particle size of ATRA nanoparticles in
      nanosuspensions reduced from 337 nm to 155 nm as the injection velocity increased
      and the polydispersity index was 0.45-0.50. The morphology of ATRA nanoparticles
      varied with the different concentration of ATRA solution in acetone. ATRA
      nanoparticles showed an amorphous state and stable in 6 months. It could be
      concluded that this modified precipitation method could produce stable and
      controllable ATRA nanosuspension to a certain extent, thus benefit for higher
      saturation solubility.

PMID- 16908424
TI  - Etodolac-liquid-filled dispersion into hard gelatin capsules: an approach to
      improve dissolution and stability of etodolac formulation.
AB  - The formation of melt dispersion is an effective method of increasing the
      dissolution rate of poorly soluble drugs, and hence, of improving the
      bioavailability. The carrier fusion method was used to prepare different
      dispersion of etodolac using Gelucire 44/14 and D-alpha-tocopheryl polyethylene
      glycol 1000 succinate (TPGS). The physical characteristics of the binary systems
      were determined by differential scanning calorimetry (DSC), infrared spectroscopy
      (IR). The release rate from the resulting dispersion was determined from
      dissolution studies by use of USP dissolution apparatus II (paddle method). The
      dissolution rate of etodolac is increased in all the dispersion systems compared
      to that of pure drug. A liquid dispersion system of etodolac (20%) and Gelucire
      44/14: TPGS blend (80%), in different ratios, was also prepared. The capsule
      formulation was subjected to stability studies at different temperature and
      humidity conditions as per ICH guidelines. Physical and chemical properties of
      the dispersion didn't change during a period of storage at room temperature and
      at 4 degrees C, 0% RH. It was found that etodolac was chemically stable against
      the effects of temperature and humidity. However, the relative humidity and
      storage time exerted an effect on the dissolution behavior of etodolac. The
      changes in dissolution behavior after storage under conditions of high humidity
      and temperature might be related to the formation of etodolac microcrystal and to
      water absorption by the carrier during storage. It is predicted that acceptable
      shelf-lives should result when moisture-resistant packaging is used for
      pharmaceutical formulations of this type.

PMID- 16908425
TI  - Micronization and polymorphic conversion of tolbutamide and barbital by rapid
      expansion of supercritical solutions.
AB  - Rapid expansion of supercritical solutions (RESS) was applied to tolbutamide and
      barbital. The solubility in supercritical CO2 was determined to estimate the
      extraction efficiency roughly by a simple method and accurately by a direct
      spectrophotometric technique. The latter revealed that the solubility of
      tolbutamide was a function of applied pressure and temperature and was
      proportional to the pressure. No significant difference in solubility between
      polymorphic Forms I and II of tolbutamide was detected. Tolbutamide and barbital
      particles produced by the RESS were characterized by size distribution
      measurement, polymorph identification and morphological evaluation. Significant
      size reduction to micron or sub-micron level with narrow size distribution was
      achieved, while conventional mechanical grinding had only slight effect. The
      particle size was greatly affected by both extraction and expansion conditions.
      The lower the extraction temperature was, the smaller was the mean particle size.
      Higher extraction pressure resulted in smaller mean particle size when compared
      at the same extraction temperature. The mean particle size was reduced by
      lowering the spray nozzle temperature, by lowering the expansion chamber
      temperature, by increasing the CO2 amount per spray, and by increasing the
      exhaust gas flow rate. The RESS processing realized the polymorphic conversion as
      well. As for tolbutamide, three polymorphs (Forms I, II, and IV) out of four
      could be produced by changing the extraction conditions, and in the case of
      barbital, one polymorph (Form II) out of three was produced consistently.

PMID- 16908426
TI  - Towards a universal dissolution medium for carbamazepine.
AB  - The aim of this study was to develop a dissolution medium for assessment of
      various carbamazepine (CBZ) formulations with different strengths. The design of
      a system inhibiting transformation of the anhydrous CBZ (CBZ A) to the dihydrate
      form (CBZ D), with minimum surface-active properties and suitable sink was
      investigated. The effect of pH, different concentrations of sodium lauryl
      sulphate (SLS), polyvinylpyrrolidone (PVP), and methyl cellulose (MC) on
      dissolution rate, solubility, dissolution solubility, and polymorphic
      transformation of CBZ was assessed. Solution-mediated transformation of CBZ A
      into CBZ D was monitored using optical microscopy, Fourier transform infrared
      spectroscopy and differential scanning calorimetry. Results showed that different
      strengths (100, 200, 400 mg) of the same CBZ tablet formulation exhibited
      different dissolution patterns, in 1% SLS (USP system). Such differences were
      reduced in 0.5% SLS solution which provided sufficient sink for up to 200 mg CBZ.
      It was also shown that solubility of CBZ A could not be detected in the media
      under study (water, SGF, SIF, and SLS solutions) due to its rapid transformation
      into CBZ D. The use of 3% PVP solution protected CBZ A from conversion for 75
      min, while 0.01% MC completely inhibited the transformation up to 24 h.
      Therefore, a medium consisting of 0.5% SLS and 0.01% MC was selected. The medium
      provided: a) protection against transformation of CBZ A to CBZ D, b) increased
      solubility of CBZ A (204 mg % compared to 128 mg % of CBZ D in 0.5% SLS), c)
      suitable sink for up to 400 mg CBZ and d) overlapping dissolution profiles of
      various strengths of the same CBZ formulation. The suggested system may be a step
      in the way of solving CBZ dissolution problems that forced the USP to specify two
      similar dissolution tests with two different limits for conventional 200 mg CBZ
      tablets.

PMID- 16908429
TI  - An improved method using densitometry for evaluating severity of laser
      photocoagulation induced CNV.
AB  - Laser photocoagulation induced choroidal neovascularization currently is the most
      effective model available for the study of this disease in terms of efficacy of
      new drugs and therapies. Previously, evaluating the extent of choroidal
      neovascularization using this model was time-consuming and required the use of
      experienced personnel. We describe a new method for simple and rapid evaluation
      of laser induced choroidal neovascularization using densitometry. Fluorescein
      angiograms of a laser photocoagulated rat eye were scanned into a computer.
      Densitometry software subsequently was used to calculate the severity of the
      laser lesions. The densitometry method proved effective for calculating the
      extent of laser induced choroidal neovascularization. In addition, this method
      was more rapid than visual evaluations and less likely to produce errors.

PMID- 16908430
TI  - Using microwave irradiation in Marchi's method for demonstrating degenerated
      myelin.
AB  - Conventional methods for histological preparation of degenerated myelin are time
      consuming and difficult. The purpose of our study was to shorten the time
      required for the procedure and to obtain better quality results for light
      microscopic demonstration of degenerated myelin in the central and peripheral
      nervous systems by using microwave irradiation. Rat brain and sciatic nerve were
      used for the study. The middle cerebral artery was occluded and the sciatic nerve
      was cut to produce myelin degeneration. Marchi's method was used for staining
      degenerated myelin. Fixation for light microscopy that would take two days using
      the conventional procedure was completed in 16.5-18.5 min using microwave
      irradiation. While staining of degenerated myelin requires 10 days for the
      conventional Marchi method, we decreased it to 7 h for brain tissue and 1 h for
      sciatic nerve by using the microwave oven. Moreover, a better quality preparation
      was achieved in the groups stained under microwave irradiation than those
      prepared by the conventional method.

PMID- 16908431
TI  - Sensitive fluorescence in situ hybridization signal detection in maize using
      directly labeled probes produced by high concentration DNA polymerase nick
      translation.
AB  - The signal produced by fluorescence in situ hybridization (FISH) often is
      inconsistent among cells and sensitivity is low. Small DNA targets on the
      chromatin are difficult to detect. We report here an improved nick translation
      procedure for Texas red and Alexa Fluor 488 direct labeling of FISH probes.
      Brighter probes can be obtained by adding excess DNA polymerase I. Using such
      probes, a 30 kb yeast transgene, and the rp1, rp3 and zein multigene clusters
      were clearly detected.

PMID- 16908432
TI  - Comparison of multiplex ligation dependent probe amplification to
      immunohistochemistry for assessing HER-2/neu amplification in invasive breast
      cancer.
AB  - The HER-2/neu transmembrane tyrosine kinase receptor is both a prognostic marker
      and a therapeutic target for breast cancer. Accurate determination of HER-2/neu
      status is a prerequisite for selecting breast tumors for HER-2/neu immunotherapy
      or for taxan based chemotherapy. Unfortunately, there is no consensus concerning
      how this determination should be reached. We compared assessment of HER-2/neu
      status using Multiplex ligation-dependent probe amplification (MLPA) and
      immunohistochemistry (IHC). The patient group comprised 60 Indonesian breast
      cancers patients. IHC was performed on paraffin sections using the CB11 antibody
      from Novocastra. Results were scored according to the Hercept test. For MLPA, DNA
      was extracted from frozen samples, PCR amplified with a probe set containing
      three hemi-primer sets for the HER-2 locus and another nine control probes spread
      over chromosome 17 and other chromosomes, and analyzed on a gene scanner. A ratio
      above two for at least two HER-2 locus probes compared to the control probes was
      regarded as amplification. IHC for HER-2/neu was negative in 36 cases, and 24
      cases (40%) showed expression. Seven, eight and nine of the latter cases were 1+,
      2+ and 3+ positive, respectively. Forty-seven cases showed no amplification by
      MLPA, and 13 cases (22%) were amplified. Comparison of IHC and MPLA showed that
      none of the 36 IHC-negative or seven IHC 1+ cases was amplified. Five of the
      eight (63%) 2+ cases were amplified, and eight of nine (89%) of the IHC 3+ tumors
      showed gene amplification by MLPA assay. For HER-2/neu, there is a good
      correlation between gene amplification detected by MLPA and overexpression by IHC
      in invasive breast cancer. It appears that MLPA can detect the HER-2 amplified
      cases in the IHC 2+ class. Because MLPA is quick and inexpensive, it is an
      attractive method for detecting HER-2/neu amplification in daily laboratory
      practice.

PMID- 16908433
TI  - Atomic force microscopy in biology: technology and techniques.
AB  - In this review, I describe the biological applications of the atomic force
      microscope (AFM). The historical background and the development of the microscope
      are described. The AFM can operate in many different modes relevant to biological
      systems including topography, chemical analysis, and forces relevant at the
      biological length scale (single cell to DNA dimensions and pico to nano Newton
      forces). A limited number of examples from the literature are described to
      illustrate some of the many capabilities of this microscope. The aim is to give
      an introduction of the technique to the inexperienced in this rapidly growing
      field.

PMID- 16908434
TI  - New embedding medium for sectioning undecalcified bone.
AB  - Methylmethacrylate (MMA) is the most commonly used embedding medium for
      sectioning undecalcified bone; however, a number of problems exist with its use
      in a research laboratory. MMA requires a long infiltration time and temperature
      control, and it reacts with many polymers. We used Kleer Set resin as an
      alternative embedding medium for sectioning undecalcified bone specimens.
      Fluorochrome labeled bone specimens were sectioned transversely using a ground
      section technique and longitudinally on a sledge macrotome. The slides were
      viewed using both transmitted light and epifluorescence microscopy. High quality
      sections were obtained using Kleer Set resin for both sectioning techniques. We
      have shown that this new embedding medium is simpler, safer, quicker to use and
      does not interfere with visualization of fluorochromes.

PMID- 16908435
TI  - Unexpected photobleaching of Alexa 488 in a fixed bacterial sample during 2
      photon excitation.
AB  - A sample of fixed bacterial cells was examined by immunofluorescence microscopy
      using an Alexa 488 conjugated secondary antibody for visualization. Excitation
      using visible light confirmed the expected photostability of this fluorophore;
      however, when using 2-photon excitation, Alexa 488 was rapidly and substantially
      photobleached. The unexpected instability of Alexa 488 under certain conditions
      may have deleterious consequences if not anticipated and accommodated in
      experimental protocols.

PMID- 16908437
TI  - Analysis of herbicides: demonstration of the utility of enzyme immunoassay
      verification by HPLC.
AB  - Evidence has accumulated that herbicides in the environment present a significant
      health hazard to the population. Therefore, the levels of heavily used substances
      such as atrazine and simazine and their metabolites need to be regularly
      assessed. The objective was to develop a rapid and simple tube ELISA procedure
      suitable for use in field studies and non-specialized laboratories. The antisera
      used were polyclonal antibodies raised in sheep against atrazine or simazine
      amido caproic acid conjugated to bovine serum albumin. The antibodies were first
      used to construct a two-step competitive ELISA procedure in 96-well microtitre
      plates. The 96-well format was then adapted to a coated-tube enzyme immunoassay,
      by immobilization of hapten-gelatine conjugates on polystyrene tubes. This
      enabled the colour to be read using a basic spectrophotometer. Soil samples were
      collected from agricultural and non-agricultural sites in Poland. Atrazine and
      simazine were extracted by liquid extraction from soil and assayed by tube ELISA.
      In addition, the samples were extracted by solid-phase extraction before analysis
      by HPLC. The immunoassays and chemical analysis were carried out by different
      individuals who were unaware of each other's results, which were then compared at
      the end of the study. Correlation of the two methods was excellent, with R=98.7
      and 81.3 for atrazine and simazine, respectively. The immunoassay yielded the
      same order of results without having to perform solid-phase extraction before
      analysis. The study has demonstrated that the simple antigen-coated tube assay
      provides a cost-effective and valuable screening test. Comparison with the more
      elaborate, heavily labour-intensive HPLC analysis demonstrated that the results
      obtained by the simpler enzyme-immunoassay tests were within the same order.

PMID- 16908438
TI  - Sensitive biomarker of polycyclic aromatic hydrocarbons (PAHs): urinary 1
      hydroxyprene glucuronide in relation to smoking and low ambient levels of
      exposure.
AB  - The study was conducted in a Chinese population with occupational or
      environmental exposures to polycyclic aromatic hydrocarbons (PAHs). A total of
      106 subjects were recruited from coke-oven workers (workers), residents in a
      metropolitan area (residents) and suburban gardeners (gardeners). All subjects
      were monitored twice for their personal exposures to PAHs. The biological samples
      were collected for measurements of 1-hydroxypyrene (1-OHP) and cotinine in urine.
      The geometric means of personal exposure levels of pyrene, benz(a)anthracene
      (BaA) and benzo(a)pyrene (BaP) in workers were 1.470, 0.978 and 0.805 microg m-3,
      respectively. The corresponding levels in residents were 0.050, 0.034 and 0.025
      microg m-3; and those in gardeners were 0.011, 0.020 and 0.008 microg m-3,
      respectively. The conjugate of 1-OHP with glucuronide (1-OHP-G) is the
      predominant form of pyrene metabolite in urine and it showed strong associations
      with exposures not only to pyrene, but also to BaA, BaP and total PAHs. Most
      importantly, a significant difference in 1-OHP-G was even detected between the
      subgroups with exposures to BaP at < 0.010 and > 0.010 but < 0.020 microg m-3,
      suggesting that 1-OHP-G is a good marker that can be used for the risk assessment
      of BaP exposure at levels currently encountered in ambient air. Furthermore,
      multiple regression analyses of 1-OHP-G on PAHs exposure indicated that cigarette
      smoke was a major confounding factor and should be considered and adjusted for
      while using 1-OHP to estimate PAHs exposure.

PMID- 16908440
TI  - New ultrasensitive 32P-postlabelling method for the analysis of 3,N4-etheno-2'
      deoxycytidine in human urine.
AB  - Etheno-DNA adducts are generated from exogenous carcinogens such as vinyl
      chloride and urethane and also from endogenous lipid peroxidation products such
      as trans-4-hydroxy-2-nonenal (HNE). The present authors and others have
      established that 1,N6-ethenodeoxyadenosine (epsilondA) and 3,N4
      ethenodeoxycytidine (epsilondC) are present in human urine and could be explored
      as biomarkers for monitoring whole-body oxidative stress. The present study
      reports on a new ultrasensitive 32P-postlabelling/thin-layer chromatography (TLC)
      method for the analysis of epsilondC as deoxynucleoside in human urine. The urine
      samples were purified and enriched on a solid-phase silica C-18 column followed
      by a semi-preparative reverse-phase high-performance liquid chromatography. The
      purified sample was labelled with a multisubstrate deoxyribonucleoside kinase
      from Drosophila melanogaster (Dm-dNK) in the presence of 5'-bromo-2'-deoxyuridine
      (BrdU) as internal standard. The absolute sensitivity of the method was 0.1 fmol
      epsilondC detectable in 500 microl of human urine. The analysis of human urine
      samples from 15 healthy volunteers revealed a mean epsilondC level of 2.49+/-1.76
      (SD) fmol micromol-1 creatinine (range 0.66-6.42). By this non-invasive method,
      epsilondC in human urine could be explored as a biomarker for oxidative stress
      related human diseases.

PMID- 16908441
TI  - Comparison of cholin- and carboxylesterase enzyme inhibition and visible effects
      in the zebra fish embryo bioassay under short-term paraoxon-methyl exposure.
AB  - The acute zebra fish embryo test (Danio rerio Hamilton-Buchanan, 1822) is an
      accepted bioassay to assess the toxicity of waste water that may be used for the
      replacement of testing with adult fish. It is also suggested for chemical hazard
      characterization and assessment, although only a few groups of substances have
      yet been studied. Specifically acting substances such as neurotoxic insecticides
      pose a potentially hazard for non-target fish. To establish whether the proposed
      zebra fish embryo test protocol and the inhibition of cholinesterases
      (acetylcholinesterase EC 3.1.1.7, propionylcholinesterase EC 3.1.1.8) and
      carboxylesterase (EC 3.1.1.1) enzymes can be used in a similar fashion for hazard
      characterization and risk assessment of chemicals and environmental samples, two
      types of experiments were conducted. Visual effects of exposure to the
      organophosphate metabolite paraoxon-methyl after 24 and 48 h in the zebra fish
      embryo test system were analysed with the use of an inverse microscope (rate of
      mortality, developmental disturbances, heart rate and others). The inhibition to
      cholinesterases and carboxylesterase was also measured. Enzyme inhibition as a
      biomarker of exposure was about 70 times more sensitive than the effects in the
      zebra fish embryo test with an IC50 below 1.2 micromol compared with an EC50 of
      91 micromol. The dose-response relationships showed different curve
      characteristics with a linear increase of enzyme inhibition compared with a
      sigmoidal curve for the overt effects. Significant overt effects could only be
      seen at concentrations at which already 80% of the activities of the different
      esterases were inhibited.

PMID- 16908439
TI  - Detection of 2-amino-1-methyl-6-phenylimidazo [4,5-b]-pyridine (PhIP)-DNA adducts
      in human pancreatic tissues.
AB  - Recent epidemiological investigations have observed an association between the
      consumption of grilled or barbecued meat and an increased risk of pancreatic
      cancer, suggesting that dietary exposure to heterocyclic aromatic amines (HCA)
      may contribute to the development of this disease. 2-Amino-1-methyl-6
      phenylimidazo [4,5-b]-pyridine (PhIP) is the most abundant HCA found in well-done
      and grilled meats. To determine whether HCA-induced DNA damage is present in the
      human pancreas, immunohistochemistry and computer-assisted image analysis were
      used to measure PhIP-DNA adducts in 54 normal pancreatic tissues (N) from persons
      without pancreatic cancer and in 38 normal adjacent pancreatic tissues (A) and in
      39 cancer tissues (T) from 68 patients with pancreatic adenocarcinoma. PhIP-DNA
      adducts were detected in 53 N, 34 A and 39 T samples. Mean values (+/-SD) of the
      absorbency for PhIP staining were 0.22+/-0.04, 0.24+/-0.04, and 0.24+/-0.03 for
      N, A, and T samples, respectively (p=0.004). Using the median absorbency (0.21)
      of the samples from normal controls as the cut-off, 71% of A and 77% of T
      tissues, compared with 48% of N tissues, were distributed in the higher range
      (p=0.009). The odds ratio of pancreatic cancer was 3.4 (95% confidence interval
      1.5-7.5, p=0.002) for individuals with a higher level of PhIP-DNA adducts. This
      is the first report of the detection of PhIP-DNA adducts in human pancreatic
      tissue samples obtained from patients with unknown exposure to HCA. Although
      limited by the small sample size, these preliminary results suggest that PhIP
      exposure may contribute to human pancreatic cancer development.

PMID- 16908442
TI  - Identification and preliminary validation of novel biomarkers of acute hepatic
      ischaemia/reperfusion injury using dual-platform proteomic/degradomic approaches.
AB  - Hepatic ischaemia/reperfusion (I/R), a major cause of liver damage associated
      with multiple trauma, haemorrhagic and septic shock, and liver transplantation,
      contributes significantly to multiple organ failure. Development of novel
      sensitive biomarkers that detect early stages of liver damage is vital for
      effective management and treatment of ischaemic liver injury. By using high
      throughput immunoblotting and cation-anion exchange chromatography/reversed-phase
      liquid chromatography-tandem mass-spectrometry, we identified several hepatic
      proteins, including argininosuccinate synthase (ASS) and estrogen
      sulfotransferase (EST-1), which were degraded in the liver and rapidly released
      into circulation during I/R injury. ASS accumulated in serum within 10 min,
      reached a steady state at 30 min, and persisted up until 3 h after reperfusion
      following 30 min of total hepatic ischaemia. EST-1 appeared rapidly in blood and
      attained maximum within 1 hour followed by a decline at 3 h of reperfusion. No
      ASS or EST-1 protein was detected in serum of control or sham operated rats. ASS
      and EST-1 exhibited greater sensitivity and specificity toward I/R liver injury
      as compared with alanine aminotransferase (ALT), an established marker of
      hepatocellular necrosis. In contrast, serum ASS and EST-1 were undetectable in
      rats with chronic alcoholic liver disease, while the levels of ALT protein were
      significantly increased. In addition, ASS, but not EST-1 or ALT accumulated in
      blood only 6 h after treatment with hepatotoxic combination of lipopolysaccharide
      and D-galactosamine. These data demonstrate the utility of ASS and EST-1 as novel
      sensitive and specific biomarkers of acute liver ischaemic injury for prospective
      clinical studies.

PMID- 16908443
TI  - Reliability of biomarkers of iron status, blood lipids, oxidative stress, vitamin
      D, C-reactive protein and fructosamine in two Dutch cohorts.
AB  - Biomarkers are widely used in epidemiology, yet there are few reliability studies
      to assess the appropriateness of using these biomarkers for the assessment of
      exposure-disease relationships. The aim of the study was to assess the
      reliability of 20 biomarkers in serum collected from two Dutch centres (Utrecht
      and Bilthoven) participating in the European Prospective Investigation into
      Cancer and Nutrition (EPIC) at two points several years apart. Blood samples were
      collected from 30 men from Bilthoven and 35 women from Utrecht. Ferritin, total
      iron, total iron-binding capacity, transferrin saturation, transferrin, C
      reactive protein, bilirubin, cholesterol, triglycerides, apo lipoprotein-A, apo
      lipoprotein-B, high-density lipoproteins, low-density lipoproteins, uric acid,
      creatinine, reactive oxygen metabolites, the ferric-reducing ability of plasma,
      protein thiol oxidation, fructosamine, and vitamin D biomarkers in serum were
      analysed from the blood samples at the two points of time. For all biomarkers,
      except C-reactive protein, there were no substantial changes in the mean levels
      over time. Uric acid, ferritin, creatinine, HDL, and apo lipoprotein-B levels
      consistently showed the highest reliability for men and women (intra-class
      correlation = 0.69-0.86). Among women, the ferric-reducing ability of plasma, and
      protein thiol oxidation had poor reliability; and among men iron-related
      biomarkers (except serum ferritin) had poor reliability. With the exception of a
      few gender-specific differences, most of the 20 biomarkers performed well and can
      be considered to have sufficient reliability to be used in future cohort studies.

PMID- 16908445
TI  - Lung inflammation in rats following subchronic exposure to cigarette mainstream
      smoke.
AB  - Female Sprague-Dawley rats were exposed to mainstream smoke from standard
      reference cigarettes and a nontobacco cellulose cigarette for 35 days. Whole
      smoke and smoke fractions were investigated. Lung inflammation was evaluated by
      differentiation of bronchoalveolar lavage cells and lymphocytes in thoracic lymph
      nodes. Histopathological changes in the nose and larynx were assessed. Results
      showed that the particulate phase of cigarette mainstream smoke is mostly
      responsible for inflammation in the lung (neutrophil increase up to 240-fold) and
      hyperplastic and metaplastic epithelial changes in the larynx, whereas irritative
      volatile constituents in the gas phase are mostly responsible for changes in the
      nose.

PMID- 16908446
TI  - Oropharyngeal aspiration of a silica suspension produces a superior model of
      silicosis in the mouse when compared to intratracheal instillation.
AB  - Instillation of crystalline silica into the lungs of mice is a common
      experimental model of pulmonary fibrosis. Typically, a suspension of silica in
      saline is injected into the trachea via intubation or surgical tracheostomy.
      These techniques require a high degree of technical skill, have a lengthy
      training period, and can suffer from a high failure rate. In oropharyngeal
      aspiration, a droplet of liquid is placed in the animal's mouth while
      simultaneously holding its tongue (to block the swallow reflex) and pinching its
      nose shut, forcing it to breathe through its mouth, aspirating the liquid. To
      determine whether oropharyngeal aspiration (OA) could replace intratracheal
      instillation (IT) in a model of silica-induced fibrosis, a comparison was
      performed. Crystalline silica was introduced into the lungs of male C57BL/6 mice
      by the IT or OA procedure, and the resulting inflammation and fibrosis was
      assessed after 3 weeks. IT and OA instillation of silica both resulted in
      neutrophilic inflammation and fibrotic changes, including interstitial fibrosis
      and dense fibrotic foci. Mice treated via IT demonstrated a few large lesions
      proximal to conducting airways with little involvement of the distal parenchyma
      and large interanimal variability. In contrast, OA resulted in a diffuse
      pathology with numerous fibrotic foci distributed throughout the lung parenchyma,
      which is more representative of human fibrotic lung disease. OA- but not IT
      treated mice exhibited significantly increased lung collagen content.
      Furthermore, the interanimal variability within the OA group was significantly
      less than in the IT group. Oropharyngeal aspiration should be considered as an
      alternative to intratracheal instillation of silica and other particulates in
      studies of respiratory toxicity and lung disease.

PMID- 16908447
TI  - Tissue inhibitor of metalloproteinase-3 is up-regulated by transforming growth
      factor-beta1 in vitro and expressed in fibroblastic foci in vivo in idiopathic
      pulmonary fibrosis.
AB  - Idiopathic pulmonary fibrosis (IPF) is characterized by fibroblast expansion and
      extracellular matrix accumulation. However, the mechanisms involved in matrix
      remodeling have not been elucidated. In this study, the authors aimed to evaluate
      the expression of the tissue inhibitors of matrix metalloproteinases (TIMPs) in
      human fibroblasts and whole tissues from IPF and normal lungs. They also
      determined the role of mitogen-activated protein kinase (MAPK) in TIMP3
      expression. TIMP1, TIMP2, and TIMP3 were highly expressed in lung fibroblasts.
      Transforming growth factor (TGF)-beta1, a profibrotic mediator, induced strong up
      regulation of TIMP3 at the mRNA and protein levels. The authors examined whether
      the MAPK pathway was involved in TGF-beta1-induced TIMP3 expression. TGF-beta1
      induced the phosphorylation of p38 and extracellular signal-regulated kinase
      (ERK)1/2. Biochemical blockade of p38 by SB203580, but not of the ERK MAPK
      pathway, inhibited the effect of this factor. The effect was also blocked by the
      tyrosine kinase inhibitor genistein and by antagonizing TGF-beta1 receptor type I
      (activin-linked kinase [ALK5]). In IPF tissues TIMP3 gene expression was
      significantly increased and the protein was localized to fibroblastic foci and
      extracellular matrix. Our findings suggest that TGF-beta1-induced TIMP3 may be an
      important mediator in lung fibrogenesis.

PMID- 16908448
TI  - Altered airway responsiveness in adult sheep born prematurely: effects of
      allergen exposure.
AB  - The aim of this study was to determine the effects of preterm birth per se on
      airway function in adult sheep. Preterm birth was induced at approximately 0.89
      of term. At approximately 1 year of age the authors measured pulmonary resistance
      (RL) and airway responsiveness before and after house dust mite (HDM) challenge.
      Mature preterm sheep tended to have greater baseline RL than controls (P = .12):
      the smaller preterm sheep showed significantly greater RL than controls following
      bronchoconstrictor challenge. Preterm animals tended to have greater baseline
      total blood leukocyte count (P = .06). It was concluded that preterm sheep,
      especially with low postnatal growth, have greater airway responsiveness to
      bronchoconstrictor and higher baseline RL.

PMID- 16908449
TI  - Asbestos-induced activation of cell signaling pathways in human bronchial
      epithelial cells.
AB  - Using respiratory epithelial cells transfected with either superoxide dismutase
      (SOD) or catalase, the authors tested the hypothesis that the activation of the
      epidermal growth factor (EGF) receptor signal pathway after asbestos exposure
      involves an oxidative stress. Western blotting using phospho-specific antibodies
      demonstrated that the EGF receptor kinase inhibitor PD153035 decreased both the
      phosphorylation of extracellular signal-regulated kinase (ERK)1/2 and its
      upstream signal pathway, including mitogen-activate protein kinase/ERK kinase
      (MEK)1/2. Similarly, the MEK1/2 kinase inhibitor PD98059 also demonstrated the
      ability to decrease phosphorylation of ERK1/2. Crocidolite-induced
      phosphorylation of EGF receptor, ERK1/2, and MEK1/2 was reduced by transfection
      of BEAS-2B cells with a catalase vector, supporting a participation of oxidative
      stress in this pathway. These results show that crocidolite can activate the
      phosphorylation of EGF receptor and its downstream cell signal pathway in BEAS-2B
      cells and this is associated with the oxidative stress presented by the fibers.

PMID- 16908450
TI  - Toluene diisocyanate (TDI) induces production of inflammatory cytokines and
      chemokines by bronchial epithelial cells via the epidermal growth factor receptor
      and p38 mitogen-activated protein kinase pathways.
AB  - Toluene diisocyanate (TDI) is known as one of causes of occupational asthma and
      hypersensitivity pneumonitis. To investigate the stimulatory effect on bronchial
      epithelial cells in response to TDI, the authors examined production of cytokines
      by the bronchial epithelial cell line BEAS-2B and intercellular signal
      transduction stimulated by TDI-human serum albumin (HSA) conjugate. The
      production of interleukin (IL)-8, granulocyte-macrophage colony-stimulating
      factor (GM-CSF), and regulated on activation normal T cell expressed and secreted
      (RANTES) from the bronchial epithelial cells were augmented by the TDI-HSA
      conjugate. Extracellular signal-regulated kinase (Erk) 1/2 and p38 mitogen
      activated protein kinase (MAPK) were phosphorylated by the TDI-HSA conjugate.
      AG1478, SB203580, and dexamethasone prevented augmentation of these cytokine
      production. TDI-HSA conjugate did not augment release of epidermal growth factor
      (EGF) ligands from BEAS-2B. These results suggest that TDI directly induces
      production of proinflammatory cytokines and chemokines through p38 MAPK and EGF
      receptor (EGFR)-Erk pathway without an autocrine mechanism. Thus, TDI was shown
      to have a stimulatory effect on bronchial epithelial cells, suggesting the potent
      role of bronchial epithelial cells in TDI-induced asthma.

PMID- 16908451
TI  - Developmental changes in respiratory mechanics in the neonatal rat.
AB  - The rat lung undergoes rapid changes during the first several weeks of life.
      Respiratory function on neonatal rats was performed to determine if physiologic
      alterations coincides with classically described lung growth, and morphologic and
      morphometric changes. The authors examined respiratory mechanics during normal
      postnatal lung development in the rat utilizing both a forced oscillation
      technique, which partitions the mechanical properties of the lung tissue from the
      airways, as well as pressure-volume (PV) curves to assess lung elasticity.
      Respiratory function testing was performed on each postnatal days of life 10 to
      20. The PV curves were characterized by a leftward shift over days 10 to 16,
      followed by a shift back to the right over days 17 to 20. Both tissue damping (G)
      and elastance (H) decreased from days of life 10 to 15, and then equilibrated
      from days 15 to 21. Hysteresivity (=G/H) at positive end-expiratory pressure
      (PEEP) = 1 and 3 cm H2O declined significantly with age. The effect of PEEP was
      significantly greater in the younger animals than in the older animals. The
      respiratory function assessments coincide well with the classically described
      periods of lung growth. These studies provide a normal baseline for correlating
      changes in structural with respiratory function.

PMID- 16908452
TI  - Exposure assessment methods for a study of mortality and cancer morbidity in
      relation to specific petroleum industry exposures.
AB  - In 1987 a Canadian company implemented an exposure tracking and health
      information system. The exposure tracking method aligned closely with published
      concepts for describing workplace exposure, with over 1800 similar exposure
      groups being used to describe occupational exposures. The database has been
      actively maintained and is subject to a number of quality checks. Recently, the
      company initiated a cancer morbidity study, with one objective being to examine
      whether the exposure tracking data could be used to reconstruct exposure
      estimates for the cohort. Five agents--hydrogen sulfide, petroleum coke/spent
      catalyst, hydrocarbon solvents and fuels, hydrocarbon lubricants, and an index
      for exposure to operations derived from noise exposure--were selected for
      development of occupational exposure estimates for each cohort member. The cohort
      consisted of workers first employed between January 1964 and December 1994 and
      who were employed for at least 1 year. Work history records were associated with
      a similar exposure group, using human resources data and knowledge of local
      industrial hygienists. Only employees with >90% duration of their work history
      assigned were kept in the cohort (25,292 people out of a possible 25,617). For
      each similar exposure group inventory, the substances were identified that
      contributed to each of the five agents being studied. Exposure estimates before
      1987 were modified using historic occupational exposure limits. Rules were
      created to sum the exposure from multiple substances found in any one similar
      exposure group. The validity of exposure estimates was tested via comparison with
      results documented in industrial hygiene survey reports. Industrial hygienists
      who were unaware of the derived exposure estimates evaluated several hundred
      industrial hygiene surveys and prepared benchmark information. The two lists were
      then evaluated for concordance, which was found to be significantly different
      from that occurring by chance. We conclude that the process described can create
      valid exposure estimates for use in epidemiology studies.

PMID- 16908453
TI  - Development of a job exposure matrix (JEM) for the textile industry in Shanghai,
      China.
AB  - We developed a job exposure matrix (JEM) for the Shanghai textile industry
      constructed along three axes: industry sector, textile process, and hazardous
      agent. We assessed 35 different categories of dust, chemical, and physical agents
      for 149 textile processes within nine industry sectors: cotton, cotton/synthetic,
      cotton/other (nonsynthetic), wool, silk, synthetic, mineral, other mixed (e.g.,
      wool and synthetic), and nonproduction. The JEM was constructed from two
      components: a priori assessment of the textile process by a team of U.S.
      industrial hygienists, and the prevalence of exposures reported by Chinese
      industrial hygienists in specific textile processes within the factory. The JEM
      was applied to an ongoing case-cohort study of cancer in women textile workers.
      The JEM assessed only dichotomous exposure (ever/never), and could be coupled
      with cumulative exposure by years of employment. The most common exposures in
      cotton mills were cotton dust and solvent exposures. Dyeing processes had the
      highest frequency of exposures, including solvents, acids, bases and caustics,
      bleaching agents, dyes, dye chemicals and intermediates, and formaldehyde. Only
      two processes were identified with formaldehyde exposure, beck dyeing and resin
      finishing. The most prevalent exposures among the subcohort, occurring in more
      than 60% of the women, were electromagnetic fields, lubricants, and cotton dust.
      More than one-third of subcohort subjects were also exposed to synthetic fiber
      dust, and slightly less than one-third of women were exposed to endotoxin. This
      JEM could be applicable for epidemiologic research in other textile industries.

PMID- 16908454
TI  - UV air cleaners and upper-room air ultraviolet germicidal irradiation for
      controlling airborne bacteria and fungal spores.
AB  - In-room air cleaners (ACs) and upper-room air ultraviolet germicidal irradiation
      (UVGI) are engineering control technologies that can help reduce the
      concentrations of airborne bacteria and fungal spores in the indoor environment.
      This study investigated six different types of ACs and quantified their ability
      to remove and/or inactivate airborne bacteria and fungal spores. Four of the air
      cleaners incorporated UV lamp(s) into their flow path. In addition, the efficacy
      of combining ACs with upper-room air UVGI was investigated. With the ventilation
      system providing zero or six air changes per hour, the air cleaners were tested
      separately or with the upper-room air UVGI system in operation in an 87-m3 test
      room. Active bacteria cells and fungal spores were aerosolized into the room such
      that their numbers and physiologic state were comparable both with and without
      air cleaning and upper-room air UVGI. In addition, the disinfection performance
      of a UV-C lamp internal to one of the ACs was evaluated by estimating the
      percentage of airborne bacteria cells and fungal spores captured on the air
      filter medium surface that were inactivated with UV exposure. Average airborne
      microbial clean air delivery rates (CADRm) varied between 26-981 m3 hr-1
      depending on the AC, and between 1480-2370 m3 hr-1, when using air cleaners in
      combination with upper-room air UVGI. Culturing, direct microscopy, and optical
      particle counting revealed similar CADRm. The ACs performed similarly when
      challenged with three different microorganisms. Testing two of the ACs showed
      that no additional air cleaning was provided with the operation of an internal UV
      C lamp; the internal UV-C lamps, however, inactivated 75% of fungal spores and
      97% of bacteria cells captured in the air filter medium within 60 min.

PMID- 16908455
TI  - Behavior of the GABIE, 3M 3500, PerkinElmer Tenax TA, and RADIELLO 145 diffusive
      samplers exposed over a long time to a low concentration of VOCs.
AB  - Diffusive sampling is particularly suited to determine time-weighted average
      volatile organic compound (VOC) concentration in occupational hygiene and
      environmental air monitoring. The purpose of this study was to measure the
      sampling rate variation of four different samplers in a special use--the exposure
      to a low concentration of volatile organic compound (10 to 200 ppb) for a long
      period (1 to 14 days). PerkinElmer tube-type adsorbent was packed with Tenax TA
      and RADIELLO cartridge packed with Carbograph 4. Badge-type activated carbon
      diffusive samplers 3M 3500 and GABIE were exposed to the same controlled
      atmospheres of benzene as meta-xylene (BTX) during the same exposure times.
      Performance samplers were observed for variability of uptake rates according to
      concentration levels, exposure duration, back diffusion, and competition
      phenomena at the adsorption sites. Particular benzene behavior has been noted for
      the thermally desorbable tube-type diffusive sampler: the measured sampling rates
      decrease with time following an exponential profile. With badge-type active
      charcoal diffusive samplers, the uptake rates were found to be highly stable and
      unaffected by time exposure. Overall, in the region of a few tens of ppb, for
      long-time exposure and for the lightest compounds, 3M 3500 and GABIE diffusive
      samplers seem the most appropriate diffusive sampling technique in terms of
      performance and facility in use.

PMID- 16908457
TI  - Histomorphology of renal dysplasia--an autopsy study.
AB  - A retrospective analysis of pediatric autopsies in the past 18 years was done
      with the aim of studying the histomorphology of renal dysplasia. Renal dysplasia
      comprised 150 (3.66%) of the 4,099 pediatric autopsies from 20 weeks of gestation
      to 1 year of life. Primitive ducts with the fibromuscular collar, the sine qua
      non of renal dysplasia, was seen in all cases. Lobar disorganization and cysts
      were seen in all cases except for the 7 cases of hypodysplasia. Other elements
      were seen in varying proportions: cartilage in 33.7%, bone in 1.08%, thickening
      of basement membrane of the primitive ducts in 64.13%, extramedullary
      hematopoiesis in 98.9%, nerve twigs in 72.8%, and nodular renal blastema in 2.17%
      cases. In unilateral multicystic dysplasia/renal agenesis, the contralateral
      kidney showed abnormalities in 44.45% and 47.37% of cases, respectively.

PMID- 16908456
TI  - Melanotic neuroectodermal tumor of infancy: clinical, radiological, and
      pathological features.
AB  - We present a case of a 4-month-old female infant with a maxillary melanotic
      neuroectodermal tumor of infancy (MNTI) and review the pooled data from previous
      publications on this entity. The literature to date comprises 378 reported cases
      from 1918 to the present, from which data on the presence or absence of
      metastatic disease was available in 311, and on the presence or absence of local
      recurrence in 165. These pooled data suggest a local recurrence rate of 36% with
      metastasis occurring in 7% of cases. At present, the optimal management includes
      complete surgical excision with clear margins, but there are no reliable
      histopathological or molecular features to predict the biological behavior in
      individual cases.

PMID- 16908458
TI  - Plexiform neurofibroma in type 1 neurofibromatosis.
AB  - A 13-year-old African-American girl was admitted to the hospital for surgery. She
      was diagnosed with Type I neurofibromatosis at the age of 1 year after she was
      noted to have multiple cafe au lait spots. Her past medical history included a
      history of neurofibroma in the base of the brain, treated with radiation therapy
      and ventriculoperitoneal shunt, as well as a recent diagnosis of bilateral optic
      gliomas, treated with chemotherapy. Family history was negative for
      neurofibromatosis.

PMID- 16908459
TI  - Risk of germ cell malignancy in children with XY intersex versus isolated
      cryptorchidism by immunohistochemistry.
AB  - The risk of subsequent development of testicular germ cell neoplasia is related
      to presence of underlying developmental defects such as cryptorchidism, in which
      the risk is around 0.5%, and XY intersex with abdominal testes, in which the risk
      may be as high as 20-25%. We examined the hypothesis that the increased risk of
      germ cell malignancy in intersex testes with Y chromosome was a direct
      consequence of an abnormal increase in number of PLAP/CD117+ immature germ cells
      into postnatal life. Archival cases of uncomplicated cryptorchidism (CO) and XY
      intersex (INT) were identified and anonymized, and a subgroup of aged-matched
      cases had sections immunostained with placental alkaline phosphatase (PLAP) and
      CD117. From a total of 89 intersex and 105 cryptorchid cases identified, a power
      calculation to detect a 20% difference in expression between groups (alpha =
      0.05, power = 80%) determined that 18 intersex and 36 cryptorchid cases were
      required. Thus, 58 cases were examined, median age 3 (range birth-11) years,
      including 39 CO and 19 INT. The prevalence of any PLAP+ germ cells was 2/39
      (5.1%) versus 3/19 (15.7%), respectively. (Z = 1.4, p = 0.17). In contrast, 94%
      of cases showed presence of any CD117+ germ cells, but the frequency of CD117+
      cells was not significantly different between groups (t = 0.56, p = 0.58). CD117
      and PLAP identify different populations of germ cells in pediatric testes. The
      extent of increased risk of malignancy in XY INT is not simply related to
      increased numbers of immature PLAP+/CD117+ germ cells present; additional factors
      play a pathogenic role.

PMID- 16908460
TI  - Exogenous lipoid pneumonia superinfected with acid-fast bacilli in infants: a
      report of nine cases.
AB  - Super-infection of an exogenous lipoid pneumonia by nontuberculous mycobacteria
      has been described in the literature. It produces a distinctive histologic
      picture with suppurative, noncaseating granulomas surrounding lipid vacuoles
      containing acid-fast bacilli. Mainly isolated cases have been found, but seldom
      in children. We describe a series of 9 children with similar histological
      findings. All our patients were under 1 year of age, malnourished, and with
      chronic respiratory symptoms. The diagnosis, based on the characteristic
      histology with acid-fast rods, was established at autopsy in 4 cases, on
      lobectomy specimens in 4 and by open lung biopsy in 1. Mycobacterium fortuitum
      chelonei was cultured in 1 case. Gastro-esophageal reflux was documented in all 4
      cases in which it was explored. Aspiration of lipid gastric contents or of oil
      given as medication can result in exogenous lipoid pneumonia, which in turn
      becomes super-infected with mycobacteria. Recognition of the distinctive
      histology permits the diagnosis of this complication.

PMID- 16908461
TI  - Histopathological features of testicular regression syndrome: relation to patient
      age and implications for management.
AB  - Testicular regression syndrome (TRS) represents a congenital condition in which
      no normal testicular tissue can be identified following exploration for a
      clinically impalpable testis. A spectrum of pathological findings may be present
      but there is little literature systematically examining these features. We
      searched a pediatric histopathology database to identify cases of TRS, and the
      histopathological findings were reviewed and pooled with those of all previously
      published smaller series. A total of 117 cases were identified during the period
      (1989-2004), median age 2 (range birth-12) years. In 52 (44%) a nodule was
      identified macroscopically, median maximum diameter 0.5 (range 0.1-2.0) cm.
      Microscopic hemosiderin-laden macrophages were present in 85 (73%), dystrophic
      calcification in 52 (44%), residual testicular tubules in 12 (10%), vas deferens
      in 71 (61%), and epididymal tissue in 39 (33%). The prevalence of hemosiderin
      laden macrophages and dystrophic calcification were significantly greater in
      cases < or =3 years (84% versus 64% and 55% versus 32%, respectively). But there
      was no significant difference in the frequency of other findings between the
      younger and older age groups; in particular, the presence of residual testicular
      tubules was similar (7% versus 13%, respectively). Furthermore, there was no
      significant correlation between identification of a macroscopically distinct
      nodule and presence of residual tubular structures, tubules being identified in 6
      of the 65 cases in which no clearly identifiable nodule was seen macroscopically.
      The presence of hemosiderin-laden macrophages and foci of dystrophic
      calcification showed a positive association. TRS is associated with specific
      histopathological features, the findings being consistent with changes secondary
      to intrauterine testicular torsion. Residual testicular tubules are found in 10%
      of cases regardless of the presence or absence of a macroscopically identifiable
      nodule.

PMID- 16908462
TI  - Developing a quality criteria framework for patient decision aids: online
      international Delphi consensus process.
AB  - OBJECTIVE: To develop a set of quality criteria for patient decision support
      technologies (decision aids). DESIGN AND SETTING: Two stage web based Delphi
      process using online rating process to enable international collaboration.
      PARTICIPANTS: Individuals from four stakeholder groups (researchers,
      practitioners, patients, policy makers) representing 14 countries reviewed
      evidence summaries and rated the importance of 80 criteria in 12 quality domains
      on a 1 to 9 scale. Second round participants received feedback from the first
      round and repeated their assessment of the 80 criteria plus three new ones. MAIN
      OUTCOME MEASURE: Aggregate ratings for each criterion calculated using medians
      weighted to compensate for different numbers in stakeholder groups; criteria
      rated between 7 and 9 were retained. RESULTS: 212 nominated people were invited
      to participate. Of those invited, 122 participated in the first round (77
      researchers, 21 patients, 10 practitioners, 14 policy makers); 104/122 (85%)
      participated in the second round. 74 of 83 criteria were retained in the
      following domains: systematic development process (9/9 criteria); providing
      information about options (13/13); presenting probabilities (11/13); clarifying
      and expressing values (3/3); using patient stories (2/5); guiding/coaching (3/5);
      disclosing conflicts of interest (5/5); providing internet access (6/6); balanced
      presentation of options (3/3); using plain language (4/6); basing information on
      up to date evidence (7/7); and establishing effectiveness (8/8). CONCLUSIONS:
      Criteria were given the highest ratings where evidence existed, and these were
      retained. Gaps in research were highlighted. Developers, users, and purchasers of
      patient decision aids now have a checklist for appraising quality. An instrument
      for measuring quality of decision aids is being developed.

PMID- 16908463
TI  - Health status and the five-factor personality traits in a nationally
      representative sample.
AB  - The authors' objective was to determine the association between the 'big-five'
      personality traits and mental and physical disorders among adults in the United
      States. The Midlife Development in the United States Survey, a nationally
      representative sample of 3032 adults ages 25-74, was used to determine the
      association between the five-factor traits of personality and common mental and
      physical disorders. Findings are consistent with and extend previous results
      showing that conscientiousness is associated with significantly reduced
      likelihood of a wide range of mental and physical disorders among adults in the
      general population, and inversely that neuroticism is associated with increased
      rates. Among adults with physical illnesses, associations were found between
      personality and likelihood of physical limitations, especially conscientiousness.
      These findings provide a framework upon which research on complex causal
      processes may proceed. Thus future research attention might profitably be
      directed to conscientiousness-relevant processes, such as adherence to health and
      treatment recommendations and internalization of healthy societal norms for
      sensible health-related behavior.

PMID- 16908464
TI  - 'When suppression backfires': the ironic effects of suppressing eating-related
      thoughts.
AB  - Based on Wegner's Ironic Processing Theory, this study examines the effects of
      suppressing eating-related thoughts in a sample of 77 female students. A
      distinction was made between disinhibited restrainers (high dietary
      restraint/high disinhibition), inhibited restrainers (high dietary restraint/low
      disinhibition) and low restrainers. Results indicate that disinhibited
      restrainers used thought suppression more often and were the only group to show a
      rebound effect for eating-related thoughts after suppression. No effects of
      suppression on willingness and desire to eat emerged. Hence, thought suppression
      may be counterproductive at least for a subgroup of restrainers and may fuel
      eating-related preoccupations. More research is required to evaluate effects on
      eating behaviour.

PMID- 16908465
TI  - Constructions of sexual relationships: a study of the views of young people in
      Catalunia, England and Slovakia and their health implications.
AB  - Q methodology was applied to investigate the views of young people from
      Catalunia, England and Slovakia regarding sexual relationships and their health
      implications. The Q sorts of 188 16-18-year-olds from these three diverse
      European regions were reduced by Q factor analysis to six clear accounts. These
      accounts are presented in relation to three emergent themes: (a)
      traditionalism/liberalism; (b) locus of responsibility; and (c) the relationship
      between sex and love, and these discursive themes are discussed in relation to
      health-salient criteria such as awareness of sex-related risk and corresponding
      implications for conduct.

PMID- 16908466
TI  - Mister in-between: a case study of masculine identity and health-related
      behaviour.
AB  - The study of young men's health-related behaviour offers an opportunity to
      examine the links between masculine identity and social behaviour. This article
      presents a case study of a 19-year-old man living in London, who describes
      himself as different to his peers on several important dimensions, including his
      engagement in health-related behaviours. The case study demonstrates the
      importance of health-related social behaviours such as drinking, drug use,
      physical activity, sport and sexual behaviour in the construction of a masculine
      identity. This case study also reveals that the way in which men position
      themselves in relation to different discourses of masculinity can have important
      implications not only for their masculine identities, but also for their health
      related behaviour.

PMID- 16908467
TI  - Predictors of unprotected sex with non-cohabitating primary partners among
      sheltered and low-income housed women in Los Angeles County.
AB  - This study investigated associations of substance use, relationship abuse and HIV
      self-protective behavior with unprotected sex among 290 impoverished women with a
      non-cohabitating primary partner. Unprotected sex was associated with having a
      physically or psychologically abusive partner among low-income housed women, and
      having an abusive partner who also drank to intoxication among women living in
      shelters. Indicators of HIV self-protective behavior were associated with less
      frequent unprotected sex among sheltered women, even after accounting for abuse
      and substance use within the relationship. Results suggest the need for HIV
      prevention interventions to address the problems of partner substance use and
      relationship abuse.

PMID- 16908468
TI  - Effects of quality of life and coping on depression among adults living with
      HIV/AIDS.
AB  - This prospective study examined the effect of maladaptive coping strategies and
      psychological quality of life (QOL) on depression at two time points in a diverse
      sample of persons living with HIV/AIDS (N = 85). The use of maladaptive coping
      strategies to deal with the stress of living with HIV/AIDS, particularly engaging
      in various kinds of avoidant behaviors, was significantly associated with greater
      depression at baseline and increased depression at three months. QOL was the
      single most important predictor of depression. In an effort to develop effective
      clinical methods aimed at decreasing depression among adults living with HIV,
      future studies need to focus on improving quality of life and increasing adaptive
      coping strategies associated with the stress of living with HIV/AIDS.

PMID- 16908469
TI  - Chronic fatigue syndrome: the role of positivity to illness in chronic fatigue
      syndrome patients.
AB  - Fifty-three chronic fatigue syndrome patients treated at a complementary medical
      centre were assessed over 12 months. Measures included the Chalder Fatigue scale,
      the General Health Questionnaire (GHQ) and positivity in illness (Silver Lining
      Questionnaire, SLQ). The SLQ measured at 6 and 9 months predicted (p < .01)
      mental (but not physical) fatigue at 12 months independently of current mental
      fatigue, initial mental fatigue, duration since diagnosis and time between start
      of treatment and entry to the study. The GHQ did not predict fatigue at any time
      point. The results suggest that a caring therapeutic intervention increases
      positive interpretations of illness prior to improvements in mental fatigue, but
      that positivity does not play a causal role in the reduction of fatigue.

PMID- 16908470
TI  - Religious coping among caregivers of terminally ill cancer patients: main effects
      and psychosocial mediators.
AB  - This study investigated the association between religious coping, mental health
      and the caring experience, as well as potential explanatory mechanisms, among 162
      informal caregivers of terminally ill cancer patients. Regression analyses
      indicated that, controlling for socio-demographic variables, more use of positive
      religious coping strategies was associated with more burden, yet, also more
      satisfaction. In contrast, more use of negative religious coping strategies was
      related to more burden, poorer quality of life and less satisfaction, and
      correlated with an increased likelihood of Major Depressive Disorder and anxiety
      disorders. In a number of models, negative religious coping was related to
      outcomes through its relationship with social support, optimism and self
      efficacy. Implications for research and healthcare are discussed.

PMID- 16908471
TI  - A narrative view of art therapy and art making by women with breast cancer.
AB  - Art therapy (with an art therapist) and art making (without an art therapist)
      show promise as avenues for psychosocial support for women with breast cancer.
      The purpose of this study was to gain an in-depth understanding of how 17 women
      with breast cancer in Canada and the USA used art therapy and their own art
      making to address their psychosocial needs, focusing particularly on meaning
      making. Narrative analysis of interviews yielded four storylines: Art and Art
      Therapy as a Haven; Getting a Clearer View; Clearing the Way Emotionally; and
      Enhancing and Enlivening the Self. The storylines show existence being affirmed,
      confirmed and proclaimed through visual artistic expression and meaning making
      being achieved through physical acts of making.

PMID- 16908472
TI  - Social comparison processes in autobiographies of adult cancer survivors.
AB  - Cancer survivors often compare their situations to other survivors' situations.
      However, types of social comparison processes used and resulting outcomes are not
      clearly delineated. This study explores usage and consequences of three social
      comparison styles (downward, upward and parallel) of adult cancer survivors in
      free narratives, using content analysis of 30 autobiographical books by survivors
      ranging in age from 30-70 (M = 54, SD = 10.04); 43 percent prostate cancer, 17
      percent breast cancer and 40 percent other cancers. Overall, cancer survivors
      used more parallel comparisons than directional comparisons, followed by upward
      comparisons. Each type of comparison was associated with different kinds of
      positive and negative consequences.

PMID- 16908473
TI  - Patients' experiences of daily living with a pacemaker: a grounded theory study.
AB  - The purpose of this study was to examine patients' experiences of daily living
      with a pacemaker. A total of 13 pacemaker patients (seven women) aged 22-82 (mean
      = 59.2) years were interviewed. The informants had had a pacemaker from 0.5 to 33
      (mean 13.1) years. The grounded theory method was the basis for collection and
      analysis of the data. The results of the analysis of the semi-structured
      interviews showed that variations in 'perceived social participation' and
      'emotional state', the two core categories, were related to four qualitatively
      different ways of experiencing daily living after pacemaker implantation.

PMID- 16908474
TI  - What is good qualitative research? A first step towards a comprehensive approach
      to judging rigour/quality.
AB  - Qualitative research has an enormous amount to contribute to the fields of
      health, medicine and public health but readers and reviewers from these fields
      have little understanding of how to judge its quality. Work to date accurately
      reflects the complexity of the theoretical debate required but may not meet the
      needs of practitioners attempting to apply qualitative work in reviews of
      evidence. This article describes a simple, practitioner-focused framework for
      assessing the rigour of qualitative research that attempts to be inclusive of a
      range of epistemological and ontological standpoints. An extensive review of the
      literature, contributions from expert groups and practitioners themselves lead to
      the generation of two core principles of quality: transparency and systematicity,
      elaborated to summarize the range of techniques commonly used, mirroring the flow
      of the research process. The complexities discovered are only summarized here.
      Finally, outstanding issues such as 'how much transparency is enough?', are
      flagged up.

PMID- 16908475
TI  - Social sharing of emotion in anticipation of cardiac surgery: effects on
      preoperative distress.
AB  - This study examined associations between social sharing of emotions, social
      support and preoperative psychological distress. Social sharing was
      operationalized in terms of quantity and quality. Quantity of social sharing was
      measured daily using a diary method. Quality of social sharing was measured with
      the Quality of Sharing Inventory. Participants were 157 hospitalized Greek
      patients. Hierarchical regression analysis showed that controlling for distress
      on admission, quality of social sharing was negatively related to distress one
      day before surgery (p < .01). No effects were found for quantity of social
      sharing. Results emphasize the importance of studying qualitative aspects of
      emotional disclosure.

PMID- 16908476
TI  - Long-term outcome of social skills intervention based on interactive LEGO play.
AB  - LEGO building materials have been adapted as a therapeutic modality for
      increasing motivation to participate in social skills intervention, and providing
      a medium through which children with social and communication handicaps can
      effectively interact. A 3 year retrospective study of long-term outcome for
      autistic spectrum children participating in LEGO therapy (N = 60) compared
      Vineland Adaptive Behavior Scale socialization domain (VABS-SD) and Gilliam
      Autism Rating Scale social interaction subscale (GARS-SI) scores preand post
      treatment with a matched comparison sample (N = 57) who received comparable non
      LEGO therapy. Although both groups made significant gains on the two outcome
      measures, LEGO participants improved significantly more than the comparison
      subjects. Diagnosis and pre-treatment full-scale IQ scores did not predict
      outcome scores; however, Vineland adaptive behavior composite, Vineland
      communication domain, and verbal IQ all predicted outcome on the VABS-SD,
      especially for the LEGO therapy group. Results are discussed in terms of
      implications for methods of social skills intervention for autistic spectrum
      disorders.

PMID- 16908477
TI  - A case study of the use of a structured teaching approach in adults with autism
      in a residential home in Greece.
AB  - In November 2001, the Greek Society for the Protection of Autistic People (GSPAP)
      established the first residence for people with autism in Greece, following the
      guidelines of structured teaching and the TEACCH method with all 12 of the
      residents. Using interview questionnaires and systematic naturalistic
      observations, this case study explored the effectiveness of the training
      programme in the residence for the 12 adolescents and adults with autism, who had
      never received any other intervention or training. The instruments used for the
      evaluation were the Childhood Autism Rating Scale, the Vineland Adaptive Behavior
      Scales and structured observations. The categories evaluated were personal
      independence, social abilities and functional communication. After a period of 6
      months the results showed significant progress in these three areas of
      functioning for all of the residents. The implications of the results in
      particular for further research and service development in Greece are discussed.

PMID- 16908478
TI  - Quantitative assessment of autistic symptomatology in preschoolers.
AB  - Given a growing emphasis on early intervention for children with autism, valid
      quantitative tools for measuring treatment response are needed. The Social
      Responsiveness Scale (SRS) is a brief (15-20 minute) quantitative measure of
      autistic traits in 4-to 18-year-olds, for which a version for 3-year-olds was
      recently developed. We obtained serial SRS measurements on 73 preschool children
      with (n = 51) and without (n = 22) autism spectrum conditions. Inter-rater
      reliability (mothers and teachers) and test-retest reliability were of the order
      of 0.75 (Pearson's r). There was substantial agreement between SRS scores and (1)
      the Vineland Adaptive Behavior Composite (Pearson's r = -0.86) and (2) scores for
      social impairment on the Autism Diagnostic Interview-Revised (r = 0.63). Overall,
      quantitative autistic trait scores tended to improve over time in preschoolers,
      irrespective of treatment conditions. We conclude that it is possible to obtain
      reliable quantitative measurements of autistic social impairment in preschoolers,
      suitable for assessing treatment response.

PMID- 16908479
TI  - Recognition of schematic facial displays of emotion in parents of children with
      autism.
AB  - Performance on an emotional labeling task in response to schematic facial
      patterns representing five basic emotions without the concurrent presentation of
      a verbal category was investigated in 40 parents of children with autism and 40
      matched controls. 'Autism fathers' performed worse than 'autism mothers', who
      performed worse than controls in decoding displays representing sadness or
      disgust. This indicates the need to include facial expression decoding tasks in
      genetic research of autism. In addition, emotional expression interactions
      between parents and their children with autism, particularly through play, where
      affect and prosody are 'physiologically' exaggerated, may stimulate development
      of social competence. Future studies could benefit from a combination of stimuli
      including photographs and schematic drawings, with and without associated verbal
      categories. This may allow the subdivision of patients and relatives on the basis
      of the amount of information needed to understand and process social-emotionally
      relevant information.

PMID- 16908480
TI  - Theory of mind and central coherence in adults with high-functioning autism or
      Asperger syndrome.
AB  - The study investigated theory of mind and central coherence abilities in adults
      with high-functioning autism (HFA) or Asperger syndrome (AS) using naturalistic
      tasks. Twenty adults with HFA/AS correctly answered significantly fewer theory of
      mind questions than 20 controls on a forced-choice response task. On a narrative
      task, there were no differences in the proportion of mental state words between
      the two groups, although the participants with HFA/AS were less inclined to
      provide explanations for characters' mental states. No between-group differences
      existed on the central coherence questions of the forced-choice response task,
      and the participants with HFA/AS included an equivalent proportion of
      explanations for non-mental state phenomena in their narratives as did controls.
      These results support the theory of mind deficit account of autism spectrum
      disorders, and suggest that difficulties in mental state attribution cannot be
      exclusively attributed to weak central coherence.

PMID- 16908481
TI  - Social attribution processes and comorbid psychiatric symptoms in children with
      Asperger syndrome.
AB  - The factors that place children with Asperger syndrome at risk for comorbid
      psychiatric symptoms, such as anxiety and depression, remain poorly understood.
      We investigated the possibility that the children's emotional and behavioral
      difficulties are associated with social information and attribution processing.
      Participants were children with either Asperger syndrome (n = 31) or typical
      development (n = 33).To assess social information and attribution processing,
      children responded to hypothetical social vignettes. They also completed self
      report measures of social difficulties and psychological functioning. Their
      parents provided information on social competence and clinical presentation.
      Children with Asperger syndrome showed poor psychosocial adjustment, which was
      related to their social information and attribution processing patterns.
      Cognitive and social-cognitive abilities were associated with aspects of social
      information processing tendencies, but not with emotional and behavioral
      difficulties. Results suggest that the comorbid symptoms of children with
      Asperger syndrome may be associated with their social perception, understanding,
      and experience.

PMID- 16908482
TI  - The quality of life of young men with Asperger syndrome: a brief report.
AB  - Factors influencing quality of life for persons with Asperger syndrome are not
      yet understood. Men, ages 18 to 21, completed the World Health Organization
      Quality Of Life measure, the Perceived Support Network Inventory, and a semi
      structured interview. Asperger syndrome affects quality of life beyond the
      obvious social impact. The 12 men with Asperger syndrome reported a significantly
      lower social and physical quality of life than did the 13 men in the control
      group. Education, living arrangements, and number of friends were remarkably
      similar between groups. Those with Asperger syndrome had less positive employment
      experiences and showed more preference for solitary activities. Interventions
      need to be based on a holistic model.

PMID- 16908483
TI  - The Childhood Asperger Syndrome Test (CAST): test-retest reliability.
AB  - The Childhood Asperger Syndrome Test (CAST) is a 37-item parental self-completion
      questionnaire to screen for autism spectrum conditions in research. Good test
      accuracy was demonstrated in studies with primary school aged children in
      mainstream schools. The aim of this study was to investigate the test-retest
      reliability of the CAST. Parents of 1000 children in years 1-6 in five mainstream
      primary schools in Cambridgeshire received the CAST. A second identical
      questionnaire was posted to respondents after approximately 2 weeks. Both
      mailings generated 136 responses. Agreement above and below a screening cut-point
      of 15 was investigated. The kappa statistic for agreement (< 15 versus > or = 15)
      was 0.70, and 97 percent (95 percent CI: 93-99 percent) of children did not move
      across the cut-point of 15. The correlation between the two test scores was 0.83
      (Spearman's rho). The CAST has shown good test-retest reliability, and now
      requires further investigation in a high-scoring sample.

PMID- 16908484
TI  - Letters to the editors.

PMID- 16908485
TI  - Clinical observations in children with autistic spectrum disorders.

PMID- 16908486
TI  - Cytokine storm in a phase 1 trial of the anti-CD28 monoclonal antibody TGN1412.
AB  - Six healthy young male volunteers at a contract research organization were
      enrolled in the first phase 1 clinical trial of TGN1412, a novel superagonist
      anti-CD28 monoclonal antibody that directly stimulates T cells. Within 90 minutes
      after receiving a single intravenous dose of the drug, all six volunteers had a
      systemic inflammatory response characterized by a rapid induction of
      proinflammatory cytokines and accompanied by headache, myalgias, nausea,
      diarrhea, erythema, vasodilatation, and hypotension. Within 12 to 16 hours after
      infusion, they became critically ill, with pulmonary infiltrates and lung injury,
      renal failure, and disseminated intravascular coagulation. Severe and unexpected
      depletion of lymphocytes and monocytes occurred within 24 hours after infusion.
      All six patients were transferred to the care of the authors at an intensive care
      unit at a public hospital, where they received intensive cardiopulmonary support
      (including dialysis), high-dose methylprednisolone, and an anti-interleukin-2
      receptor antagonist antibody. Prolonged cardiovascular shock and acute
      respiratory distress syndrome developed in two patients, who required intensive
      organ support for 8 and 16 days. Despite evidence of the multiple cytokine
      release syndrome, all six patients survived. Documentation of the clinical course
      occurring over the 30 days after infusion offers insight into the systemic
      inflammatory response syndrome in the absence of contaminating pathogens,
      endotoxin, or underlying disease.

PMID- 16908487
TI  - T-cell costimulation--biology, therapeutic potential, and challenges.

PMID- 16908488
TI  - Volunteers at risk.

PMID- 16908489
TI  - Glucose, insulin, and acute myocardial infarction.

PMID- 16908490
TI  - The second Euro Heart Survey on acute coronary syndromes: Characteristics,
      treatment, and outcome of patients with ACS in Europe and the Mediterranean Basin
      in 2004.
AB  - AIMS: Our study aimed to examine the management of acute coronary syndromes (ACS)
      in Europe and the Mediterranean basin, and to compare adherence to guidelines
      with that reported in the first Euro Heart Survey on ACS (EHS-ACS-I), 4 years
      earlier. METHODS AND RESULTS: In a prospective survey conducted in 2004 (EHS-ACS
      II), data describing the characteristics, treatment, and outcome of 6385 patients
      diagnosed with ACS in 190 medical centres in 32 countries were collected. ACS
      with ST-elevation was the initial diagnosis in 47% of patients, no ST-elevation
      in 48%, and undetermined electrocardiographic pattern in 5% of patients.
      Comparison of data collected in 2000 and 2004 showed similar baseline
      characteristics, but greater use of recommended medications and coronary
      interventions in EHS-ACS-II. Among patients with ST-elevation, the use of primary
      reperfusion increased slightly (from 56 to 64%), with a significant shift from
      fibrinolytic therapy to primary percutaneous coronary intervention (PPCI). The
      use of PPCI rose from 37 to 59% among those undergoing primary reperfusion
      therapy. Analysis of data in 34 centres that participated in both surveys showed
      even greater improvement with respect to the use of recommended medical therapy,
      interventions, and outcome. CONCLUSION: Data from EHS-ACS-II suggest an increase
      in adherence to guidelines for treatment of ACS in comparison with EHS-ACS-I.

PMID- 16908491
TI  - TRPV1 receptors and nasal trigeminal chemesthesis.
AB  - The trigeminal nerve responds to a wide variety of irritants. Trigeminal nerve
      fibers express several receptors that respond to chemicals, including TRPV1
      (vanilloid) receptors, acid-sensing ion channels, P2X (purinergic) receptors, and
      nicotinic acetylcholine receptors. In order to assess whether TRPV1 plays a role
      in responses to a broad array of substances, TRPV1 (along with green fluorescent
      protein) was expressed in human embyonic kidney cells (HEK) 293t cells which were
      then stimulated with diverse trigeminal irritants. Calcium imaging was used to
      measure responses to capsaicin, amyl acetate, cyclohexanone, acetic acid,
      toluene, benzaldehyde, (-)-nicotine, (R)-(+)-limonene, (R)-(-)-carvone, and (S)
      (+)-carvone. Three irritants (acetic acid and the 2 carvones) stimulated
      nontransfected controls. Two irritants (capsaicin and cyclohexanone) stimulated
      only transfected cells. The response could be eliminated with capsazepine, a
      TRPV1 blocker. The 5 remaining irritants were nonstimulatory in both
      nontransfected and transfected cells. Because all the compounds tested on HEK
      cells elicited neural responses from the ethmoid branch of the trigeminal nerve
      in rats, the 5 nonstimulatory compounds must do so by a non-TRPV1 receptor. These
      results suggest that TRPV1 serves as a receptor for both cyclohexanone and
      capsaicin in trigeminal nerve endings.

PMID- 16908492
TI  - Epileptogenic neocortical networks are revealed by abnormal temporal dynamics in
      seizure-free subdural EEG.
AB  - Long-term video electroencephalographic (EEG) recording is currently a routine
      procedure in the presurgical evaluation of localization-related epilepsies.
      Cortical epileptogenic zone is usually localized from ictal recordings with
      intracranial electrodes, causing a significant burden to patients and health
      care. Growing literature suggests that epileptogenic networks exhibit aberrant
      dynamics also during seizure-free periods. We examined if neocortical
      epileptogenic regions can be circumscribed by quantifying local long-range
      temporal (auto-)correlations (LRTC) with detrended fluctuation analysis of
      seizure-free ongoing subdural EEG activity in 4 frequency bands in 5 patients. We
      show here with subdural EEG recordings that the LRTC are abnormally strong near
      the seizure onset area. This effect was most salient in neocortical oscillations
      in the beta frequency band (14-30 Hz). Moreover, lorazepam, a widely used
      antiepileptic drug, exerted contrasting effects on LRTC (n = 2): lorazepam
      attenuated beta-band LRTC near the epileptic focus, whereas it strengthened LRTC
      in other cortical areas. Our findings demonstrate that interictal neuronal
      network activity near the focus of seizure onset has pathologically strong
      intrinsic temporal correlations. The observed effect by lorazepam on beta-band
      activity suggests that the antiepileptic mechanism of benzodiazepines may be
      related to the normalization of LRTC within the epileptic focus. We propose that
      this method may become a promising candidate for routine invasive and noninvasive
      presurgical localization of epileptic foci.

PMID- 16908493
TI  - Interactions of pain intensity and cognitive load: the brain stays on task.
AB  - Pain naturally draws one's attention. However, humans are capable of engaging in
      cognitive tasks while in pain, although it is not known how the brain represents
      these processes concurrently. There is some evidence for a cortical interaction
      between pain- and cognitive-related brain activity, but the outcome of this
      interaction may depend on the relative load imposed by the pain versus the task.
      Therefore, we used 3 levels of cognitive load (multisource interference task) and
      2 levels of pain intensity (median nerve stimulation) to examine how functional
      magnetic resonance imaging activity in regions identified as pain-related or
      cognitive-related responds to different combinations of pain intensity and
      cognitive load. Overall, most pain-related or cognitive-related brain areas
      showed robust responses with little modulation. However, during the more intense
      pain, activity in primary sensorimotor cortex, secondary somatosensory
      cortex/posterior insula, anterior insula, paracentral lobule, caudal anterior
      cingulate cortex, cerebellum, and supplementary motor area was modestly
      attenuated by the easy task and in some cases the difficult task. Conversely,
      cognitive-related activity was not modulated by pain, except when cognitive load
      was minimal during the control task. These findings support the notion that brain
      networks supporting pain perception and cognition can be simultaneously active.

PMID- 16908494
TI  - Changes in visual responses in the feline dLGN: selective thalamic suppression
      induced by transcranial magnetic stimulation of V1.
AB  - Transcranial magnetic stimulation (TMS) of the cortex can modify activity
      noninvasively and produce either excitatory or inhibitory effects, depending on
      stimulus parameters. Here we demonstrate controlled inhibitory effects on the
      large corticogeniculate feedback pathway from primary visual cortex to cells of
      the dorsal lateral geniculate nucleus (dLGN) that are focal and reversible
      induced by either single pulses or trains of pulses of TMS. These effects
      selectively suppress the sustained component of responses to flashed spots or
      moving grating stimuli and are the result of loss of spikes fired in tonic mode,
      whereas the number of spikes fired in bursts remain the same. We conclude that
      acute inactivation of the corticogeniculate downflow selectively affects the
      tonic mode. We found no evidence to suggest that cortical inactivation increased
      burst frequency.

PMID- 16908495
TI  - Neural bases of stereopsis across visual field of the alert macaque monkey.
AB  - Left and right retinal images of an object seen by the 2 eyes can occupy slightly
      disparate horizontal and/or vertical locations. The role of horizontal disparity
      (HD) in stereoscopic vision is well established, but the functional contribution
      of vertical disparity (VD) remains unclear. Various psychophysical studies have
      shown that HD and VD are used differently by the visual system depending on their
      location in the visual field, whether near the center of gaze or more peripheral.
      We show this horizontal/vertical distinction at the cellular level in monkey
      primary visual cortex (area V1). The range of VD encoding is reduced in central
      but not in the peripheral representation of the visual field. Moreover, neurons
      respond selectively to particular combinations of both types of disparities
      depending on the coded orientation as predicted by the disparity energy model.
      The preferred orientations of neurons near the fovea present a vertical bias that
      is well suited for stereopsis based on HD selectivity alone. In the periphery,
      instead, preferred orientations are radially biased, which allows a peripheral
      detector to convey the same depth signal based on either HD or VD. Such an
      organization has functional implications in both the perceptual and oculomotor
      domains.

PMID- 16908496
TI  - Perceived parenting style and practices and the consumption of sugar-sweetened
      beverages by adolescents.
AB  - The purpose of this study was to investigate whether perceived parenting
      practices and parenting style dimensions (strictness and involvement) are
      associated with adolescents' consumption of sugar-sweetened beverages. In this
      cross-sectional study, secondary school students (n = 383, mean age 13.5 years)
      completed a self-administered questionnaire on their consumption of sugar
      sweetened beverages, attitude, social influences, self-efficacy, habit strength,
      food-related parenting practices and the general parenting style dimensions of
      'strictness' and 'involvement'. Data were analyzed using multiple linear
      regression analyses. More restrictive parenting practices were associated with
      lower consumption of sugar-sweetened beverages (beta = -38.0 ml; 95% CI = -48.1, 
      28.0). This association was highly mediated ( approximately 55%) by attitude,
      self-efficacy and modeling from parents. Nevertheless, a significant direct
      effect remained (beta = -17.1 ml; 95% CI = -27.2, -6.90). Interactions between
      perceived parenting style and parenting practices showed that the association
      between parenting practices and sugar-sweetened beverage consumption was stronger
      among adolescents who perceived their parents as being moderately strict and
      highly involved. Parents influence their children's sugar-sweetened beverage
      consumption and should therefore be involved in interventions aimed at changing
      dietary behaviors. Interventions aimed at the promotion of healthy parenting
      practices will improve when they are tailored to the general parenting style of
      the participants.

PMID- 16908497
TI  - Young people, smoking and gender--a qualitative exploration.
AB  - Smoking among young people has become increasingly gendered. In several
      countries, smoking among adolescent girls is now higher than among adolescent
      boys. However, we have only a limited understanding of the reasons behind these
      gender patterns. This paper reports the findings from a qualitative study which
      used single-sex focus groups to explore the gendered nature of the meaning and
      function of smoking among Scottish 15- to 16-year old smokers. The study found
      that young people were ambivalent about their smoking but that this was somewhat
      different for boys and girls. These differences related to their social worlds,
      pattern of social relationships, interests, activities and concerns, the meanings
      they attached to smoking and the role smoking played in dealing with the everyday
      experience of being a boy or girl in their mid-teens. For example, boys were
      concerned about the impact of smoking on their fitness and sport, whereas girls
      were more concerned about the negative aesthetic effects such as their clothes
      and bodies smelling of smoke. Of particular importance was how smoking related in
      different ways to the gendered 'identity work' that adolescents had to undertake
      to achieve a socially and culturally acceptable image. The implications for
      programmes aimed at reducing smoking among young people, particularly the need
      for more gender-sensitive approaches, are discussed.

PMID- 16908498
TI  - Health and safety intervention with first-time mothers.
AB  - A health education program was evaluated which used child development specialists
      as home visitors and served a population of first-time mothers living in rural
      communities. The evaluation compared health and safety outcomes between
      intervention and control groups. The research staff, separate from the
      intervention staff, collected data in the homes of 156 intervention and 107
      control mothers when the infants were 6 and 12 months old. Significant group
      differences were found on health and safety outcomes. As compared with controls,
      the intervention mothers (i) had safer homes; (ii) were more likely to use birth
      control, thus had fewer pregnancies since birth of their first child; (iii)
      reported smoking fewer cigarettes; (iv) knew more about effects of smoking on
      their child's health and (v) were more likely to use health department services.
      In sum, mothers who received early education home visits from child development
      specialists experienced positive health and safety outcomes. It is highly
      recommended that a program such as this be implemented as part of health delivery
      program with new mothers and infants.

PMID- 16908499
TI  - Meta-analysis based on control of false discovery rate: combining yeast ChIP-chip
      datasets.
AB  - MOTIVATION: High-throughput microarray technology can be used to examine
      thousands of features, such as all the genes of an organism, and measure their
      expression. Two important issues of microarray bioinformatics are first, how to
      combine the significance values for each feature across experiments with high
      statistical power, and second, how to control the proportion of false positives.
      Existing methods address these issues separately, in spite of their linked usage.
      RESULTS: We present a novel method (ESP) to address the two requirements in an
      interdependent way. It generalizes the truncated product method of Zaykin et al.
      to combine only those significance values which clear their respective experiment
      specific false discovery restrictive thresholds, thus allowing us to control the
      false discovery rate (FDR) for the final combined result. Further, we introduce
      several concepts that together offer FDR control, high power, quality control and
      speed-up in meta-analysis as done by our algorithm. Computational and statistical
      methods of research synthesis like the one described here will be increasingly
      important as additional genome-wide datasets accumulate in databases. We apply
      our method to combine three well-known ChIP-chip transcription factor binding
      datasets for budding yeast to identify significant intergenic regulatory
      sequences for nine cell cycle regulating transcription factors, both with high
      power and controlled FDR.

PMID- 16908500
TI  - The ties problem resulting from counting-based error estimators and its impact on
      gene selection algorithms.
AB  - MOTIVATION: Feature selection approaches, such as filter and wrapper, have been
      applied to address the gene selection problem in the literature of microarray
      data analysis. In wrapper methods, the classification error is usually used as
      the evaluation criterion of feature subsets. Due to the nature of high
      dimensionality and small sample size of microarray data, however, counting-based
      error estimation may not necessarily be an ideal criterion for gene selection
      problem. RESULTS: Our study reveals that evaluating genes in terms of counting
      based error estimators such as resubstitution error, leave-one-out error, cross
      validation error and bootstrap error may encounter severe ties problem, i.e. two
      or more gene subsets score equally, and this in turn results in uncertainty in
      gene selection. Our analysis finds that the ties problem is caused by the
      discrete nature of counting-based error estimators and could be avoided by using
      continuous evaluation criteria instead. Experiment results show that continuous
      evaluation criteria such as generalised the absolute value of w2 measure for
      support vector machines and modified Relief's measure for k-nearest neighbors
      produce improved gene selection compared with counting-based error estimators.
      AVAILABILITY: The companion website is at
      http://www.ntu.edu.sg/home5/pg02776030/wrappers/ The website contains (1) the
      source code of all the gene selection algorithms and (2) the complete set of
      tables and figures of experiments.

PMID- 16908501
TI  - Mining frequent stem patterns from unaligned RNA sequences.
AB  - MOTIVATION: In detection of non-coding RNAs, it is often necessary to identify
      the secondary structure motifs from a set of putative RNA sequences. Most of the
      existing algorithms aim to provide the best motif or few good motifs, but
      biologists often need to inspect all the possible motifs thoroughly. RESULTS: Our
      method RNAmine employs a graph theoretic representation of RNA sequences and
      detects all the possible motifs exhaustively using a graph mining algorithm. The
      motif detection problem boils down to finding frequently appearing patterns in a
      set of directed and labeled graphs. In the tasks of common secondary structure
      prediction and local motif detection from long sequences, our method performed
      favorably both in accuracy and in efficiency with the state-of-the-art methods
      such as CMFinder. AVAILABILITY: The software is available upon request.

PMID- 16908502
TI  - Novel interrelationship between salicylic acid, abscisic acid, and PIP2-specific
      phospholipase C in heat acclimation-induced thermotolerance in pea leaves.
AB  - Increasing evidence suggests that heat acclimation and exogenous salicylic acid
      (SA) and abscisic acid (ABA) may lead to the enhancement of thermotolerance in
      plants. In this study, the roles that free SA, conjugated SA, ABA, and
      phosphatidylinositol-4,5-bisphosphate (PIP(2))-specific phospholipase C (PLC)
      play in thermotolerance development induced by heat acclimation (38 degrees C)
      were investigated. To evaluate their potential functions, three inhibitors of
      synthesis or activity were infiltrated into pea leaves prior to heat acclimation
      treatment. The results showed that the burst of free SA in response to heat
      acclimation could be attributed to the conversion of SA 2-O-D-glucose, the main
      conjugated form of SA, to free SA. Inhibition of ABA biosynthesis also resulted
      in a defect in the free SA peak during heat acclimation. In acquired
      thermotolerance assessment, the greatest weakness of antioxidant enzyme activity
      and the most severe heat injury (malondialdehyde content and degree of wilting)
      were found in pea leaves pre-treated with neomycin, a well-known inhibitor of
      PIP(2)-PLC activity. PsPLC gene expression was activated by exogenous ABA, SA
      treatments, and heat acclimation after pre-treatments with a SA biosynthesis
      inhibitor. From these results, PIP(2)-PLC appears to play a key role in free SA-
      and ABA-associated reinforcement of thermotolerance resulting from heat
      acclimation.

PMID- 16908503
TI  - Gene profiling of the red light signalling pathways in roots.
AB  - Red light, acting through the phytochromes, controls numerous aspects of plant
      development. Many of the signal transduction elements downstream of the
      phytochromes have been identified in the aerial portions of the plant; however,
      very few elements in red-light signalling have been identified specifically for
      roots. Gene profiling studies using microarrays and quantitative Real-Time PCR
      were performed to characterize gene expression changes in roots of Arabidopsis
      seedlings exposed to 1 h of red light. Several factors acting downstream of
      phytochromes in red-light signalling in roots were identified. Some of the genes
      found to be differentially expressed in this study have already been
      characterized in the red-light-signalling pathway for whole plants. For example,
      PHYTOCHROME KINASE 1 (PKS1), LONG HYPOCOTYL 5 (HY5), EARLY FLOWERING 4 (ELF4),
      and GIGANTEA (GI) were all significantly up-regulated in roots of seedlings
      exposed to 1 h of red light. The up-regulation of SUPPRESSOR OF PHYTOCHROME A
      RESPONSES 1 (SPA1) and CONSTITUTIVE PHOTOMORPHOGENIC 1-like (COP1-like) genes
      suggests that the PHYA-mediated pathway was attenuated by red light. In addition,
      genes involved in lateral root and root hair formation, root plastid development,
      phenylpropanoid metabolism, and hormone signalling were also regulated by
      exposure to red light. Interestingly, members of the RPT2/NPH3 (ROOT PHOTOTROPIC
      2/NON PHOTOTROPIC HYPOCOTYL 3) family, which have been shown to mediate blue
      light-induced phototropism, were also differentially regulated in roots in red
      light. Therefore, these results suggest that red and blue light pathways interact
      in roots of seedlings and that many elements involved in red-light-signalling
      found in the aerial portions of the plant are differentially expressed in roots
      within 1 h of red light exposure.

PMID- 16908504
TI  - Reducing stem bending increases the height growth of tall pines.
AB  - The hypothesis was tested that upper limits to height growth in trees are the
      result of the increasing bending moment of trees as they grow in height. The
      increasing bending moment of tall trees demands increased radial growth at the
      expense of height growth to maintain mechanical stability. In this study, the
      bending moment of large lodgepole pine (Pinus contorta Dougl. Ex Loud. var.
      latifolia Engelm.) was reduced by tethering trees at 10 m height to counter the
      wind load. Average bending moment of tethered trees was reduced to 38% of control
      trees. Six years of tethering resulted in a 40% increase in height growth
      relative to the period before tethering. By contrast, control trees showed
      decreased height growth in the period after tethering treatment. Average radial
      growth along the bole, relative to height growth, was reduced in tethered trees.
      This strongly suggests that mechanical constraints play a crucial role in
      limiting the height growth of tall trees. Analysis of bending moment and basal
      area increment at both 10 m and 1.3 m showed that the amount of wood added to the
      stem was closely related to the bending moment produced at these heights, in both
      control and tethered trees. The tethering treatment also resulted in an increase
      in the proportion of latewood at the tethering height, relative to 1.3 m height.
      For untethered control trees, the ratio of bending stresses at 10 m versus 1.3 m
      height was close to 1 in both 1998 and 2003, suggesting a uniform stress
      distribution along the outer surface of the bole.

PMID- 16908505
TI  - Postharvest heat and conditioning treatments activate different molecular
      responses and reduce chilling injuries in grapefruit.
AB  - A combination of hot water (a rinse at 62 degrees C for 20 s) and conditioning
      (pre-storage at 16 degrees C for 7 d) treatments synergistically reduced chilling
      injury development in grapefruit (Citrus paradisi, cv. "Star Ruby") during cold
      storage at 2 degrees C, suggesting that the treatments may activate different
      chilling tolerance responses. To study the molecular mechanisms involved,
      chilling- and conditioning-responsive genes were isolated by polymerase chain
      reaction (PCR) cDNA subtraction, cDNA libraries were constructed from hot water-
      and conditioning-treated fruit, and cDNA sequencing was used to identify putative
      stress-responsive and chilling tolerance genes. PCR cDNA subtraction revealed the
      identification of 17 chilling-responsive and heat- and conditioning-induced
      genes, and the expression patterns of 11 additional stress-related genes,
      antioxidant defensive genes, and genes encoding enzymes involved in membrane
      lipid modifications were characterized. It was found that hot water and
      conditioning treatments had little effect on gene expression by themselves, but
      rather had a priming effect, and enabled the fruit to activate their defence
      responses after subsequent exposure to chilling. RNA gel blot hybridizations
      revealed that the expression patterns of eight genes, including HSP19-I, HSP19
      II, dehydrin, universal stress protein (USP), EIN2, 1,3;4-beta-D-glucanase, and
      superoxide dismutase (SOD), were specifically regulated by the heat treatment,
      and four genes, including fatty acid desaturase2 (FAD2) and lipid transfer
      protein (LTP), were specifically regulated by the conditioning treatment.
      Furthermore, four more genes were identified, including a translation initiation
      factor (SUI1), a chaperonin, and alcohol dehydrogenase (ADH), that were commonly
      regulated by both heat and conditioning treatments. According to these data, it
      is suggested that pre-storage heat and conditioning treatments may enhance fruit
      chilling tolerance by activating different molecular mechanisms. The hot water
      treatment activates mainly the expression of various stress-related genes,
      whereas the conditioning treatment activates mainly the expression of lipid
      membrane modification enzymes.

PMID- 16908506
TI  - High-level tryptophan accumulation in seeds of transgenic rice and its limited
      effects on agronomic traits and seed metabolite profile.
AB  - Metabolic manipulation of plants to improve their nutritional quality is an
      important goal of plant biotechnology. Expression in rice (Oryza sativa L.) of a
      transgene (OASA1D) encoding a feedback-insensitive alpha subunit of rice
      anthranilate synthase results in the accumulation of tryptophan (Trp) in calli
      and leaves. It is shown here that the amount of free Trp in the seeds of such
      plants is increased by about two orders of magnitude compared with that in the
      seeds of wild-type plants. The total Trp content in the seeds of the transgenic
      plants was also increased. Two homozygous lines, HW1 and HW5, of OASA1D
      transgenic rice were generated for characterization of agronomic traits and
      aromatic metabolite profiling of seeds. The marked overproduction of Trp was
      stable in these lines under field conditions, although spikelet fertility and
      yield, as well as seed germination ability, were reduced compared with the wild
      type. These differences in agronomic traits were small, however, in HW5. In spite
      of the high Trp content in the seeds of the HW lines, metabolic profiling
      revealed no substantial changes in the amounts of other phenolic compounds. The
      amount of indole acetic acid was increased about 2-fold in the seeds of the
      transgenic lines. The establishment and characterization of these OASA1D
      transgenic lines have thus demonstrated the feasibility of increasing the Trp
      content in the seeds of rice (or of other crops) as a means of improving its
      nutritional value for human consumption or animal feed.

PMID- 16908508
TI  - Altered tapetal PCD and pollen wall development in the Arabidopsis ms1 mutant.
AB  - The Arabidopsis male sterility1 mutation results in mature anthers that are
      devoid of pollen. Meiosis and early development progress normally; however, after
      microspore release, the microspore cytoplasm and tapetum become abnormally
      granular and vacuolated, and degeneration occurs. Pollen wall development is
      seriously affected; primexine formation within the callose wall appears to occur
      normally, however, once the callose is degraded, abnormal deposits of
      electrodense material are detected which result in irregular spike-shaped
      structures, rather than the characteristic rod-like shape of the wild-type
      bacula. The internal intine wall is also reduced compared with wild type. TUNEL
      (terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling) staining
      and ultrastructural analysis have indicated that programmed cell death (PCD)
      occurs in the wild-type tapetum after microspore mitosis I. However, no signs of
      PCD are seen in the ms1 tapetum, where large autophagic vacuoles and
      mitochondrial swelling suggest that necrotic-based breakdown of the tapetum is
      occurring in the ms1 mutant rather than the normal, regulated PCD process. After
      the formation of the large, autophagic vacuole in the tapetum, TUNEL staining is
      detected in the mutant microspores, indicating that they may go through a PCD
      based breakdown as a secondary consequence of the observed tapetal aberrations.
      Based on these observations, two possible roles for MS1 can be hypothesized; MS1
      may function by modifying the transcription of tapetal-specific genes implicated
      in pollen wall development, which then regulate pollen wall material secretion
      and in turn wall development and tapetal PCD. Alternatively, the MS1 gene may
      control tapetal development by directly regulating tapetal PCD and breakdown.

PMID- 16908509
TI  - Mortality in rheumatoid arthritis. Increased in the early course of disease, in
      ischaemic heart disease and in pulmonary fibrosis.
AB  - OBJECTIVE: To examine the cause of death in a large UK inception cohort of
      rheumatoid arthritis (RA), and whether this was related to disease duration and
      severity, treatment effects or extra-articular features and complications of RA.
      METHODS: Standard clinical, laboratory, radiological and socio-economic measures
      were recorded at baseline and yearly in an inception cohort started in nine
      centres in 1986. Date and the cause of death were based on death certificates and
      the comparisons made with age and sex matched population figures. Risk factors
      for mortality were identified from baseline measures of disease. RESULTS: There
      were 459 deaths (32%) in 1429 patients followed for up to 18 yrs. Standard
      mortality ratio was 1.27. Survival was significantly lower in the first 7 yrs of
      RA. Excess mortality was seen in cardiovascular disease (31%), pulmonary fibrosis
      (4%) and lymphoma (2.3%). Baseline predictors for mortality were men, older age,
      poor function, lower socio-economic status, extra-articular features,
      comorbidity, rheumatoid factor, X-ray erosions, high-ESR and low-haemoglobin.
      CONCLUSION: There was a modest increase in mortality in RA, mainly in the first 7
      yrs. Deaths from cardiovascular disease and pulmonary fibrosis were higher than
      expected, but treatment-related deaths were low. Risk factors included less
      favourable socio-economic status, markers of disease severity and diminished
      function within the first year.

PMID- 16908510
TI  - Depression in rheumatoid arthritis--underscoring the problem.

PMID- 16908511
TI  - Initial poor quality of life and new onset of dyspepsia: results from a
      longitudinal 10-year follow-up study.
AB  - BACKGROUND: Numerous studies examining the prevalence and natural history of
      dyspepsia in the general population have been conducted. However, few have
      reported the effect of quality of life on the development of dyspepsia. A 10-year
      longitudinal follow-up study examining the effect of quality of life on
      subsequent dyspepsia was performed. METHODS: Individuals originally enrolled in a
      population-screening programme for Helicobacter pylori were contacted through a
      validated postal dyspepsia questionnaire. Baseline demographic data, quality of
      life at original study entry, and dyspepsia and irritable bowel syndrome (IBS)
      symptom data were already on file. Consent to examine primary-care records was
      sought, and data regarding non-steroidal anti-inflammatory drugs (NSAID) and
      aspirin use were obtained from these. RESULTS: Of 8407 individuals originally
      involved, 3912 (46.5%) provided symptom data at baseline and 10-year follow-up.
      Of 2550 (65%) individuals asymptomatic at study entry, 717 (28%) developed new
      onset dyspepsia at 10 years, an incidence of 2.8% per year. After multivariate
      logistic regression, lower quality of life at study entry (OR 2.63; 99% CI 1.86
      to 3.71), higher body mass index (OR per unit 1.05; 99% CI 1.02 to 1.08),
      presence of IBS at study entry (OR 3.1; 99% CI 1.51 to 6.37) and use of NSAIDs
      and/or aspirin (OR 1.32; 99% CI 0.99 to 1.75) were significant risk factors for
      new-onset dyspepsia. CONCLUSIONS: The incidence of new-onset dyspepsia was almost
      3% per year. Low quality of life at baseline exerted a strong effect on the
      likelihood of developing dyspepsia at 10 years.

PMID- 16908512
TI  - Comparative study of the intestinal mucus barrier in normal and inflamed colon.
AB  - AIM: To study the role of mucus in the spatial separation of intestinal bacteria
      from mucosa. PATIENTS AND METHODS: Mucus barrier characteristics were evaluated
      using histological material obtained by biopsy from purged colon, colon prepared
      with enema and material from untreated appendices fixed with non-aqueous Carnoy
      solution. Bacteria were evaluated using fluorescence in situ hybridization, with
      bacterial 16S RNA probes and related to the periodic acid Schiff alcian blue
      stain. Biopsies from controls (n = 20), patients with self-limiting colitis (SLC;
      n = 20), ulcerative colitis (n = 20) and 60 randomly selected appendices were
      investigated. RESULTS: The mucosal surface beneath the mucus layer was free of
      bacteria in > or =80% of the normal appendices and biopsies from controls. The
      thickness of the mucus layer and its spread decreased with increasing severity of
      the inflammation; the epithelial surface showed bacterial adherence, epithelial
      tissue defects and deep mucosal infiltration with bacteria and leucocytes.
      Bacteria and leucocytes were found within mucus in all biopsy specimens from
      patients with ulcerative colitis, SLC, and acute appendicitis. The concentration
      of bacteria within mucus was inversely correlated to the numbers of leucocytes.
      CONCLUSIONS: The large bowel mucus layer effectively prevents contact between the
      highly concentrated luminal bacteria and the epithelial cells in all parts of the
      normal colon. Colonic inflammation is always accompanied by breaks in the mucus
      barrier. Although the inflammatory response gradually reduces the number of
      bacteria in mucus and faeces, the inflammation itself is not capable of
      preventing bacterial migration, adherence to and invasion of the mucosa.

PMID- 16908513
TI  - Double cancer of gall bladder and bile duct not associated with anomalous
      junction of the pancreaticobiliary duct system.
AB  - BACKGROUND: Simultaneous double cancers of the biliary tract are rare. Most of
      them are thought to be associated with pancreaticobiliary maljunction (PBM);
      however, the characteristics of tumours without PBM are still unclear. METHODS:
      Histology, immunoreactivity with carcinoembryonic antigen, carbohydrate antigen
      19-9 and p53 and mutations in the K-ras gene were examined in tumours resected
      from cases of simultaneous double cancers of the biliary tract. RESULTS: Four
      cases of simultaneous double cancers of the biliary tract were identified among
      108 patients with biliary tract cancer (3.7%). None of the four cases associated
      with PBM, and the results of histological, immunohistochemical and genetic
      examinations differed between the bile duct and gall bladder cancers in each
      case. CONCLUSION: Even when they do not associate with PBM, double cancers in the
      biliary tract are more likely to be the result of multicentric development.

PMID- 16908514
TI  - HIV accomplices and adversaries in macrophage infection.
AB  - Cell surface and intracellular proteins in macrophages influence various steps in
      the life cycle of lentiviruses. Characterization of these restriction and/or
      cofactors is essential to understanding how macrophages become unwitting HIV
      hosts and in fact, can coexist with a heavy viral burden. Although many of the
      cellular pathways co-opted by HIV in macrophages mimic those seen in CD4+ T
      cells, emerging evidence reveals cellular constituents of the macrophage, which
      may be uniquely usurped by HIV. For example, in addition to CD4 and CCR5,
      membrane annexin II facilitates early steps in infection of macrophages, but not
      in T cells. Blockade of this pathway effectively diminishes macrophage infection.
      Viral binding engages a macrophage-centric signaling pathway and a
      transcriptional profile, including genes such as p21, which benefit the virus.
      Once inside the cell, multiple host cell molecules are engaged to facilitate
      virus replication and assembly. Although the macrophage is an enabler, it also
      possesses innate antiviral mechanisms, including apolipoprotein B mRNA-editing
      enzyme-catalytic polypeptide-like 3G (APOBEC3) family DNA-editing enzymes to
      inhibit replication of HIV. Differential expression of these enzymes, which are
      largely neutralized by HIV to protect its rebirth, is associated with resistance
      or susceptibility to the virus. Higher levels of the cytidine deaminases endow
      potential HIV targets with a viral shield, and IFN-alpha, a natural inducer of
      macrophage APOBEC expression, renders macrophages tougher combatants to HIV
      infection. These and other manipulatable pathways may give the macrophage a
      fighting chance in its battle against the virus.

PMID- 16908515
TI  - Slamming the door on unwanted guests: why preemptive strikes at the mucosa may be
      the best strategy against HIV.

PMID- 16908516
TI  - Francisella tularensis LVS evades killing by human neutrophils via inhibition of
      the respiratory burst and phagosome escape.
AB  - Francisella tularensis is a Gram-negative bacterium and the causative agent of
      tularemia. Recent data indicate that F. tularensis replicates inside macrophages,
      but its fate in other cell types, including human neutrophils, is unclear. We now
      show that F. tularensis live vaccine strain (LVS), opsonized with normal human
      serum, was rapidly ingested by neutrophils but was not eliminated. Moreover,
      evasion of intracellular killing can be explained, in part, by disruption of the
      respiratory burst. As judged by luminol-enhanced chemiluminescence and nitroblue
      tetrazolium staining, neutrophils infected with live F. tularensis did not
      generate reactive oxygen species. Confocal microscopy demonstrated that NADPH
      oxidase assembly was disrupted, and LVS phagosomes did not acquire gp91/p22(phox)
      or p47/p67(phox). At the same time, F. tularensis also impaired neutrophil
      activation by heterologous stimuli such as phorbol esters and opsonized zymosan
      particles. Later in infection, LVS escaped the phagosome, and live organisms
      persisted in the neutrophil cytosol for at least 12 h. To our knowledge, our data
      are the first demonstration of a facultative intracellular pathogen, which
      disrupts the oxidative burst and escapes the phagosome to evade elimination
      inside neutrophils, and as such, our data define a novel mechanism of virulence.

PMID- 16908517
TI  - Quantitative magnetic resonance and SPECT imaging for macrophage tissue migration
      and nanoformulated drug delivery.
AB  - We posit that the same mononuclear phagocytes (MP) [bone marrow (BM) and blood
      monocytes, tissue macrophages, microglia, and dendritic cells] which serve as
      targets, reservoirs, and vehicles for HIV dissemination, can be used as vehicles
      for antiretroviral therapy (ART). Toward this end, BM macrophages (BMM) were used
      as carriers for nanoparticle-formulated indinavir (NP-IDV), and the cell
      distribution was monitored by single photon emission computed tomography (SPECT),
      transverse relation time (T2)* weighted magnetic resonance imaging (MRI),
      histology, and gamma-scintillation spectrometry. BMM labeled with super
      paramagnetic iron oxide and/or 111indium oxine were infused i.v. into naive mice.
      During the first 7 h, greater than 86% of cell label was recorded within the
      lungs. On Days 1, 3, 5, and 7, less than 10% of BMM were in lungs, and 74-81% and
      13-18% were in liver and spleen, respectively. On a tissue volume basis, as
      determined by SPECT and MRI, BMM densities in spleen and liver were significantly
      greater than other tissues. Migration into the lymph nodes on Days 1 and 7
      accounted for 1.5-2% of the total BMM. Adoptive transfer of BMM loaded with NP
      IDV produced drug levels in lymphoid and nonlymphoid tissues that exceeded
      reported therapeutic concentrations by 200- to 350-fold on Day 1 and remained in
      excess of 100- to 300-fold on Day 14. These data show real-time kinetics and
      destinations of macrophage trafficking and demonstrate the feasibility of
      monitoring macrophage-based, nanoformulated ART.

PMID- 16908518
TI  - Function of the two Xenopus smad4s in early frog development.
AB  - Signals from the transforming growth factor beta family members are transmitted
      in the cell through specific receptor-activated Smads and a common partner Smad4.
      Two Smad4 genes (alpha and beta/10, or smad4 and smad4.2) have been isolated from
      Xenopus, and conflicting data are reported for Smad4beta/10 actions in mesodermal
      and neural induction. To further understand the functions of the Smad4s in early
      frog development, we analyzed their activities in detail. We report that Smad10
      is a mutant form of Smad4beta that harbors a missense mutation of a conserved
      arginine to histidine in the MH1 domain. The mutation results in enhanced
      association of Smad10 with the nuclear transcription corepressor Ski and leads to
      its neural inducing activity through inhibition of bone morphogenetic protein
      (BMP) signaling. In contrast to Smad10, both Smad4alpha and Smad4beta enhanced
      BMP signals in ectodermal explants. Using antisense morpholino oligonucleotides
      (MOs) to knockdown endogenous Smad4 protein levels, we discovered that Smad4beta
      was required for both activin- and BMP-mediated mesodermal induction in animal
      caps, whereas Smad4alpha affected only the BMP signals. Neither Smad4 was
      involved directly in neural induction. Expression of Smad4beta-MO in early frog
      embryos resulted in reduction of mesodermal markers and defects in axial
      structures, which were rescued by either Smad4alpha or Smad4beta. Smad4alpha-MO
      induced only minor deficiency at late stages. As Smad4beta, but not Smad4alpha,
      is expressed at high levels maternally and during early gastrulation, our data
      suggest that although Smad4alpha and Smad4beta may have similar activities, they
      are differentially utilized during frog embryogenesis, with only Smad4beta being
      essential for mesoderm induction.

PMID- 16908519
TI  - Conditions of endoplasmic reticulum stress favor the accumulation of cytosolic
      prion protein.
AB  - After signal sequence-dependent targeting to the endoplasmic reticulum (ER),
      prion protein (PrP) undergoes several post-translational modifications, including
      glycosylation, disulfide bond formation, and the addition of a
      glycosylphosphatidylinositol anchor. As a result, multiple isoforms are
      generated. Because of the intrinsic weakness of the PrP signal sequence, a
      fraction of newly synthesized molecules fails to translocate and localizes to the
      cytosol. The physiopathologic role of this cytosolic isoform is still being
      debated. Here we have shown that, in both cultured cell lines and primary
      neurons, ER stress conditions weaken PrP co-translational translocation, favoring
      accumulation of aggregation-prone cytosolic species, which retain the signal
      sequence but lack N-glycans and disulfides. Inhibition of proteasomes further
      increases the levels of cytosolic PrP. Overexpression of spliced XBP1 facilitates
      ER translocation, suggesting that downstream elements of the Ire1-XBP1 pathway
      are involved in PrP targeting. These studies reveal a link between ER stress and
      the formation of cytosolic PrP isoforms potentially endowed with novel signaling
      or cytotoxic functions.

PMID- 16908520
TI  - Regulatory interactions between ubiquinol oxidation and ubiquinone reduction
      sites in the dimeric cytochrome bc1 complex.
AB  - We have obtained evidence for conformational communication between ubiquinol
      oxidation (center P) and ubiquinone reduction (center N) sites of the yeast bc1
      complex dimer by analyzing antimycin binding and heme bH reduction at center N in
      the presence of different center P inhibitors. When stigmatellin was occupying
      center P, concentration-dependent binding of antimycin occurred only to half of
      the center N sites. The remaining half of the bc1 complex bound antimycin with a
      slower rate that was independent of inhibitor concentration, indicating that a
      slow conformational change needed to occur before half of the enzyme could bind
      antimycin. In contrast, under conditions where the Rieske protein was not fixed
      proximal to heme bL at center P, all center N sites bound antimycin with fast and
      concentration-dependent kinetics. Additionally, the extent of fast cytochrome b
      reduction by menaquinol through center N in the presence of stigmatellin was
      approximately half of that observed when myxothiazol was bound at center P. The
      reduction kinetics of the bH heme by decylubiquinol in the presence of
      stigmatellin or myxothiazol were also consistent with a model in which fixation
      of the Rieske protein close to heme bL in both monomers allows rapid binding of
      ligands only to one center N. Decylubiquinol at high concentrations was able to
      abolish the biphasic binding of antimycin in the presence of stigmatellin but did
      not slow down antimycin binding rates. These results are discussed in terms of
      half-of-the-sites activity of the dimeric bc1 complex.

PMID- 16908521
TI  - Acyl coenzyme A-binding protein augments bid-induced mitochondrial damage and
      cell death by activating mu-calpain.
AB  - Activation of calpain has been shown to occur in some contexts of cell injury and
      to be essential for loss of cell viability. Part of this may be mediated at the
      mitochondrial level. It has been demonstrated that calpain activity is necessary
      for the complete discharge of apoptosis-inducing factor from the mitochondrial
      intermembrane space and can cause the cleavage of full-length Bid to a more
      potent truncated form (Polster, B. M., Basanez, G., Etxebarria, A., Hardwick, J.
      M., and Nicholls, D. G. (2005) J. Biol. Chem. 280, 6447-6454). In this study, we
      identify acyl-CoA-binding protein (ACBP) as playing a critical role in the
      activation of calpain upon exposure of mitochondria to both full-length Bid and
      truncated Bid (t-Bid). Suppression of ACBP levels by small interfering RNA
      inhibited the t-Bid-induced activation of mitochondrial mu-calpain and release of
      apoptosis-inducing factor from the mitochondrial intermembrane space and the
      cleavage of full-length Bid to t-Bid. Moreover, ACBP required the presence of the
      peripheral benzodiazepine receptor (for which ACBP is a ligand) to be retained at
      the mitochondria, to activate mu-calpain, and to amplify Bid-induced
      mitochondrial damage.

PMID- 16908522
TI  - Wnt/beta-catenin signaling is a normal physiological response to mechanical
      loading in bone.
AB  - A preliminary expression profiling analysis of osteoblasts derived from tibia
      explants of the high bone mass LRP5 G171V transgenic mice demonstrated increased
      expression of canonical Wnt pathway and Wnt/beta-catenin target genes compared
      with non-transgenic explant derived osteoblasts. Therefore, expression of
      Wnt/beta-catenin target genes were monitored after in vivo loading of the tibia
      of LRP5 G171V transgenic mice compared with non-transgenic mice. Loading resulted
      in the increased expression of Wnt pathway and Wnt/beta-catenin target genes
      including Wnt10B, SFRP1, cyclin D1, FzD2, WISP2, and connexin 43 in both
      genotypes; however, there was a further increased in transcriptional response
      with the LRP5 G171V transgenic mice. Similar increases in the expression of these
      genes (except cyclin D1) were observed when non-transgenic mice were
      pharmacologically treated with a canonical Wnt pathway activator, glycogen
      synthase kinase 3beta inhibitor and then subjected to load. These in vivo results
      were further corroborated by in vitro mechanical loading experiments in which
      MC3T3-E1 osteoblastic cells were subjected to 3400 microstrain alone for 5 h,
      which increased the expression of Wnt10B, SFRP1, cyclin D1, FzD2, WISP2, and
      connexin 43. Furthermore, when MC3T3-E1 cells were treated with either glycogen
      synthase kinase 3beta inhibitor or Wnt3A to activate Wnt signaling and then
      subjected to load, a synergistic up-regulation of these genes was observed
      compared with vehicle-treated cells. Collectively, the in vivo and in vitro
      mechanical loading results support that Wnt/beta-catenin signaling is a normal
      physiological response to load and that activation of the Wnt/beta-catenin
      pathway enhances the sensitivity of osteoblasts/osteocytes to mechanical loading.

PMID- 16908523
TI  - Growth factor-dependent AKT activation and cell migration requires the function
      of c-K(B)-Ras versus other cellular ras isoforms.
AB  - K-Ras-negative fibroblasts are defective in their steady-state expression of MMP
      2. This occurs through c-K(B)-Ras dependent regulation of basal levels of AKT
      activity. In this report, we have extended those studies to demonstrate that in
      the absence of K-Ras expression, PDGF-BB fails to induce significant AKT
      activation, although this was not the case in N-Ras-negative cells. This
      phenotype was directly linked to PDGF-dependent cell migration. All of the
      independently immortalized K-Ras-negative cells failed to migrate upon the
      addition of PDGF. Only ectopic expression of c-K(B)-Ras, not c-K(A)-Ras nor
      oncogenic N-Ras, could restore both PDGF-dependent AKT activation and cell
      migration. Since most Ras binding partners can interact with all Ras isoforms,
      the specificity of PDGF-dependent activation of AKT and enhanced cell migration
      suggests that these outcomes are likely to be regulated through a c-K(B)-Ras
      specific binding partner. Others have published that of the four Ras isoforms,
      only K(B)-Ras can form a stable complex with calmodulin (CaM). Along those lines,
      we provide evidence that 1) PDGF addition results in increased levels of a
      complex between c-K(B)-Ras and CaM and 2) the biological outcomes that are
      strictly dependent on c-K(B)-Ras (AKT activation and cell migration) are blocked
      by CaM antagonists. The PDGF-dependent activation of ERK is unaffected by the
      absence of K(B)-Ras and presence of CaM antagonists. This is the first example of
      a linkage between a specific biological outcome, cell migration, and the activity
      of a single Ras isoform, c-K(B)-Ras.

PMID- 16908524
TI  - Pro-urokinase-type plasminogen activator is a substrate for hepsin.
AB  - Hepsin, a type II transmembrane serine protease, is strongly up-regulated in
      prostate cancer. Hepsin overexpression in a mouse prostate cancer model resulted
      in tumor progression and metastasis, associated with basement membrane
      disorganization. We investigated whether hepsin enzymatic activity was linked to
      the basement membrane defects by examining its ability to initiate the
      plasminogen/plasmin proteolytic pathway. Because plasminogen is not processed by
      hepsin, we investigated the upstream activators, urokinase-type plasminogen
      activator (uPA) and tissue-type plasminogen activator. Enzymatic assays with a
      recombinant soluble form of hepsin demonstrated that hepsin did not cleave pro
      tissue-type plasminogen activator but efficiently converted pro-uPA into high
      molecular weight uPA by cleavage at the Lys158-Ile159 (P1-P1') peptide bond. uPA
      generated by hepsin displayed enzymatic activity toward small synthetic and
      macromolecular substrates indistinguishable from uPA produced by plasmin. The
      catalytic efficiency of pro-uPA activation by hepsin (kcat/Km 4.8 x 10(5) m(-1)
      s(-1)) was similar to that of plasmin, which is considered the most potent pro
      uPA activator and was about 6-fold higher than that of matriptase. Conversion of
      pro-uPA was also demonstrated with cell surface-expressed full-length hepsin. A
      stable hepsinoverexpressing LnCaP cell line converted pro-uPA into high molecular
      weight uPA at a rate of 6.6 +/- 1.9 nm uPA h(-1), which was about 3-fold higher
      than LnCaP cells expressing lower hepsin levels on their surface. In conclusion,
      the ability of hepsin to efficiently activate pro-uPA suggests that it may
      initiate plasmin-mediated proteolytic pathways at the tumor/stroma interface that
      lead to basement membrane disruption and tumor progression.

PMID- 16908525
TI  - Sequence-specific interactions in the RNA-binding domain of Escherichia coli
      transcription termination factor Rho.
AB  - Rho factor is an essential protein that causes termination of transcription in a
      wide variety of bacteria by an RNA-dependent helicase activity. Rho is activated
      by transcripts that contain a high proportion of cytidine residues. The
      interaction between Rho and two adjacent cytidine residues within the bound RNA
      has been identified by previous crystallographic studies (Skordalakes, E., and
      Berger, J. M. (2003) Cell 114, 135-146). In this study, NMR methods were used to
      investigate the sequence dependence of the binding of oligonucleotides to the RNA
      binding domain of Rho protein (rho130). A comparison of the NMR spectra obtained
      for rho130 bound to single-stranded oligonucleotides ACTTCCA or ATTTCCA showed
      that the 5'-cytidine residue interacts with Rho at a site that is distinct from
      the CC binding site identified by crystallographic studies. Two amino acid
      residues within this new cytidine binding site, Arg(88) and Phe(89), were altered
      to Glu and Ser, respectively. These mutant forms of Rho were defective in
      transcriptional termination, suggesting that those residues play an important
      role in the activation of Rho by bound RNA.

PMID- 16908526
TI  - Phospholipid hydroxyalkenals, a subset of recently discovered endogenous CD36
      ligands, spontaneously generate novel furan-containing phospholipids lacking CD36
      binding activity in vivo.
AB  - We recently identified a novel family of oxidized choline glycerophospholipid
      (oxPC) molecular species enriched in atheroma that serve as endogenous ligands
      for the scavenger receptor CD36 (oxPC(CD36)), facilitating macrophage cholesterol
      accumulation and foam cell formation (Podrez, E. A., Poliakov, E., Shen, Z., et
      al. (2002) J. Biol. Chem. 277, 38517-38523). A high affinity CD36 recognition
      motif was defined within oxPC(CD36), an oxidatively truncated sn-2 acyl group
      with a terminal gamma-hydroxy (or oxo)-alpha,beta-unsaturated carbonyl. The fate
      of these species once formed in vivo is unknown. Here we show that a subset of
      oxPC(CD36), a phosphatidylcholine molecular species possessing sn-2 esterified
      fatty acyl hydroxyalkenal groups, can undergo a slow intramolecular cyclization
      and dehydration reaction to form novel oxPC species possessing a sn-2 acyl group
      that incorporates a terminal furyl moiety (oxPC-furan). Using high performance
      liquid chromatography with on-line tandem mass spectrometry in combination with
      unambiguous organic synthesis, we confirm that oxPC-furans, ultimately derived
      from phospholipids with sn-2 esterified docosahexaenoic, arachidonic, or linoleic
      acids, are formed during exposure of model membranes and isolated lipoproteins to
      physiological oxidant systems. In vivo generation of oxPC-furans at sites of
      enhanced oxidant stress is also demonstrated, such as within brain tissues
      following cerebral ischemia. Cell binding studies reveal that in contrast to
      their oxPC(CD36) precursors, oxPC-furans lack CD36 binding activity. Taken
      together, the present studies identify oxPC-furans as a novel family of oxidized
      phospholipids that are formed in vivo from phospholipid hydroxyalkenals but that
      lack CD36 binding activity.

PMID- 16908527
TI  - The mitochondrial intermembrane loop region of rat carnitine palmitoyltransferase
      1A is a major determinant of its malonyl-CoA sensitivity.
AB  - Carnitine palmitoyltransferase (CPT) 1A adopts a polytopic conformation within
      the mitochondrial outer membrane, having both the N- and C-terminal segments on
      the cytosolic aspect of the membrane and a loop region connecting the two
      transmembrane (TM) segments protruding into the inter membrane space. In this
      study we demonstrate that the loop exerts major effects on the sensitivity of the
      enzyme to its inhibitor, malonyl-CoA. Insertion of a 16-residue spacer between
      the C-terminal part of the loop sequence (i.e. between residues 100 and 101) and
      TM2 (which is predicted to start at residue 102) increased the sensitivity to
      malonyl-CoA inhibition of the resultant mutant protein by more than 10-fold. By
      contrast, the same insertion made between TM1 and the loop had no effects on the
      kinetic properties of the enzyme, indicating that effects on the catalytic C
      terminal segment were specifically induced by loop-TM2 interactions. Enhanced
      sensitivity was also observed in all mutants in which the native TM2-loop pairing
      was disrupted either by making chimeras in which the loops and TM2 segments of
      CPT 1A and CPT 1B were exchanged or by deleting successive 9-residue segments
      from the loop sequence. The data suggest that the sequence spanning the loop-TM2
      boundary determines the disposition of this TM in the membrane so as to alter the
      conformation of the C-terminal segment and thus affect its interaction with
      malonyl-CoA.

PMID- 16908528
TI  - Distinct action of the retinoblastoma pathway on the DNA replication machinery
      defines specific roles for cyclin-dependent kinase complexes in prereplication
      complex assembly and S-phase progression.
AB  - The retinoblastoma (RB) and p16ink4a tumor suppressors are believed to function
      in a linear pathway that is functionally inactivated in a large fraction of human
      cancers. Recent studies have shown that RB plays a critical role in regulating S
      phase as a means for suppressing aberrant proliferation and controlling genome
      stability. Here, we demonstrate a novel role for p16ink4a in replication control
      that is distinct from that of RB. Specifically, p16ink4a disrupts prereplication
      complex assembly by inhibiting mini-chromosome maintenance (MCM) protein loading
      in G1, while RB was found to disrupt replication in S phase through attenuation
      of PCNA function. This influence of p16ink4a on the prereplication complex was
      dependent on the presence of RB and the downregulation of cyclin-dependent kinase
      (CDK) activity. Strikingly, the inhibition of CDK2 activity was not sufficient to
      prevent the loading of MCM proteins onto chromatin, which supports a model
      wherein the composite action of multiple G1 CDK complexes regulates
      prereplication complex assembly. Additionally, p16ink4a attenuated the levels of
      the assembly factors Cdt1 and Cdc6. The enforced expression of these two
      licensing factors was sufficient to restore the assembly of the prereplication
      complex yet failed to promote S-phase progression due to the continued absence of
      PCNA function. Combined, these data reveal that RB and p16ink4a function through
      distinct pathways to inhibit the replication machinery and provide evidence that
      stepwise regulation of CDK activity interfaces with the replication machinery at
      two discrete execution points.

PMID- 16908529
TI  - ATR-dependent phosphorylation of DNA-dependent protein kinase catalytic subunit
      in response to UV-induced replication stress.
AB  - Phosphorylation of the DNA-dependent protein kinase catalytic subunit (DNA-PKcs)
      upon ionizing radiation (IR) is essential for cellular radioresistance and
      nonhomologous-end-joining-mediated DNA double-strand break repair. In addition to
      IR induction, we have previously shown that DNA-PKcs phosphorylation is increased
      upon camptothecin treatment, which induces replication stress and replication
      associated double-strand breaks. To clarify the involvement of DNA-PKcs in this
      process, we analyzed DNA-PKcs phosphorylation in response to UV irradiation,
      which causes replication stress and activates ATR (ATM-Rad3-related)/ATM (ataxia
      telangiectasia mutated) kinases in a replication-dependent manner. Upon UV
      irradiation, we observed a rapid DNA-PKcs phosphorylation at T2609 and T2647, but
      not at S2056, distinct from that induced by IR. UV-induced DNA-PKcs
      phosphorylation occurs specifically only in replicating cells and is dependent on
      ATR kinase. Inhibition of ATR activity via caffeine, a dominant-negative kinase
      dead mutant, or RNA interference led to the attenuation of UV-induced DNA-PKcs
      phosphorylation. Furthermore, DNA-PKcs associates with ATR in vivo and is
      phosphorylated by ATR in vitro, suggesting that DNA-PKcs could be the direct
      downstream target of ATR. Taken together, these results strongly suggest that DNA
      PKcs is required for the cellular response to replication stress and might play
      an important role in the repair of stalled replication forks.

PMID- 16908530
TI  - Syntenin-1 is a new component of tetraspanin-enriched microdomains: mechanisms
      and consequences of the interaction of syntenin-1 with CD63.
AB  - Tetraspanins are clustered in specific microdomains (named tetraspanin-enriched
      microdomains, or TERM) in the plasma membrane and regulate the functions of
      associated transmembrane receptors, including integrins and receptor tyrosine
      kinases. We have identified syntenin-1, a PDZ domain-containing protein, as a new
      component of TERM and show that syntenin-1 specifically interacts with the
      tetraspanin CD63. Detailed biochemical and heteronuclear magnetic resonance
      spectroscopy (NMR) studies have demonstrated that the interaction is mediated by
      the C-terminal cytoplasmic region of the tetraspanin and the PDZ domains of
      syntenin-1. Upon interaction, NMR chemical shift perturbations were predominantly
      localized to residues around the binding pocket of PDZ1, indicating a specific
      mode of recognition of the cytoplasmic tail of CD63. In addition, the C terminus
      of syntenin-1 has a stabilizing role in the CD63-syntenin-1 association, as
      deletion of the last 17 amino acids abolished the interaction. The CD63-syntenin
      1 complex is abundant on the plasma membrane, and the elevated expression of the
      wild-type syntenin-1 slows down constitutive internalization of the tetraspanin.
      Furthermore, internalization of CD63 was completely blocked in cells expressing a
      syntenin-1 mutant lacking the first 100 amino acids. Previous results have shown
      that CD63 is internalized via AP-2-dependent mechanisms. Hence, our data indicate
      that syntenin-1 can counteract the AP-2-dependent internalization and identify
      this tandem PDZ protein as a new regulator of endocytosis.

PMID- 16908531
TI  - Mms2-Ubc13-dependent and -independent roles of Rad5 ubiquitin ligase in
      postreplication repair and translesion DNA synthesis in Saccharomyces cerevisiae.
AB  - The Rad6-Rad18 ubiquitin-conjugating enzyme complex of Saccharomyces cerevisiae
      promotes replication through DNA lesions via three separate pathways that include
      translesion synthesis (TLS) by DNA polymerases eta and zeta and postreplicational
      repair (PRR) of discontinuities that form in the newly synthesized DNA opposite
      from DNA lesions, mediated by the Mms2-Ubc13 ubiquitin-conjugating enzyme and
      Rad5. Rad5 is an SWI/SNF family ATPase, and additionally, it functions as a
      ubiquitin ligase in the ubiquitin conjugation reaction. To decipher the roles of
      these Rad5 activities in lesion bypass, here we examine the effects of mutations
      in the Rad5 ATPase and ubiquitin ligase domains on the PRR of UV-damaged DNA and
      on UV-induced mutagenesis. Even though the ATPase-defective mutation confers only
      a modest degree of UV sensitivity whereas the ubiquitin ligase mutation causes a
      high degree of UV sensitivity, we find that both of these mutations produce the
      same high level of PRR defect as that conferred by the highly UV-sensitive
      rad5Delta mutation. From these studies, we infer a requirement of the Rad5 ATPase
      and ubiquitin ligase activities in PRR, and based upon the effects of different
      rad5 mutations on UV mutagenesis, we suggest a role for Rad5 in affecting the
      efficiency of lesion bypass by the TLS polymerases. In contrast to the role of
      Rad5 in PRR, however, where its function is coupled with that of Mms2-Ubc13, Rad5
      function in TLS would be largely independent of this ubiquitin-conjugating enzyme
      complex.

PMID- 16908532
TI  - Deposition and function of histone H3 variants in Tetrahymena thermophila.
AB  - In Tetrahymena, HHT1 and HHT2 genes encode the same major histone H3; HHT3 and
      HHT4 encode similar minor H3 variants (H3s), H3.3 and H3.4. Green fluorescent
      protein (GFP)-tagged H3 is deposited onto chromatin through a DNA replication
      coupled (RC) pathway. GFP-tagged H3.3 and H3.4 can be deposited both by a
      transcription-associated, replication-independent (RI) pathway and also weakly by
      an RC pathway. Although both types of H3s can be deposited by the RC pathway, DNA
      repair synthesis associated with meiotic recombination utilizes H3 specifically.
      The regions distinguishing H3 and H3.3 for their deposition pathways were
      identified. RC major H3 is not essential. Cells can grow without major H3 if the
      minor H3s are expressed at high levels. Surprisingly, cells lacking RI H3s are
      also viable and maintain normal nucleosome density at a highly transcribed
      region. The RC H3 is not detectably deposited by the RI pathway, even when there
      are no RI H3s available, indicating that transcription-associated RI H3
      deposition is not essential for transcription. Minor H3s are also required to
      produce viable sexual progeny and play an unexpected role in the germ line
      micronuclei late in conjugation that is unrelated to transcription.

PMID- 16908533
TI  - Asymmetric positioning of nucleosomes and directional establishment of
      transcriptionally silent chromatin by Saccharomyces cerevisiae silencers.
AB  - In Saccharomyces cerevisiae, silencers flanking the HML and HMR loci consist of
      various combinations of binding sites for Abf1p, Rap1p, and the origin
      recognition complex (ORC) that serve to recruit the Sir silencing complex,
      thereby initiating the establishment of transcriptionally silent chromatin. There
      have been seemingly conflicting reports concerning whether silencers function in
      an orientation-dependent or -independent manner, and what determines the
      directionality of a silencer has not been explored. We demonstrate that chromatin
      plays a key role in determining the potency and directionality of silencers. We
      show that nucleosomes are asymmetrically distributed around the HML-I or HMR-E
      silencer so that a nucleosome is positioned close to the Abf1p side but not the
      ORC side of the silencer. This coincides with preferential association of Sir
      proteins and transcriptional silencing on the Abf1p side of the silencer.
      Elimination of the asymmetry in nucleosome positioning at a silencer leads to
      comparable silencing on both sides. Asymmetric nucleosome positioning in the
      immediate vicinity of a silencer is independent of its orientation and genomic
      context, indicating that it is the inherent property of the silencer. Moreover,
      it is also independent of the Sir complex and thus precedes the formation of
      silent chromatin. Finally, we demonstrate that asymmetric positioning of
      nucleosomes and directional silencing by a silencer depend on ORC and Abf1p. We
      conclude that the HML-I and HMR-E silencers promote asymmetric positioning of
      nucleosomes, leading to unequal potentials of transcriptional silencing on their
      sides and, hence, directional silencing.

PMID- 16908534
TI  - The Grb2/Mek pathway represses Nanog in murine embryonic stem cells.
AB  - The homeobox gene Nanog is a key intrinsic determinant of self renewal in
      embryonic stem (ES) cells, and its repression leads ES cells to selectively
      differentiate into primitive endoderm. Although Nanog repression occurs at the
      outermost layer of ES cell aggregates independent of the leukemia inhibitory
      factor (LIF)/STAT3 pathway, it is largely undetermined what external cues and
      intracellular signals cause the event. Of interest, addition of the tyrosine
      phosphatase inhibitor, sodium vanadate, selectively repressed Nanog transcription
      without any detectable changes in upstream transcriptional regulators Oct3/4 and
      Sox2. Furthermore, sodium vanadate induced primitive endoderm differentiation,
      even in the inner cells of ES cell aggregates. Expression of Gata6 and Zfp42, two
      putative downstream Nanog effectors, was also increased and decreased by the
      addition of sodium vanadate, respectively, but these changes were eliminated by
      exogenous Nanog expression. The effects of sodium vanadate were abrogated by Grb2
      deficiency or by the addition of the Mek inhibitor, PD98059. Indeed, PD98059
      prevented Nanog repression induced by ES cell aggregation as well. Furthermore,
      transfection of a constitutive active Mek mutant into ES cells induced Nanog
      repression and primitive endoderm differentiation. These data indicate that the
      Grb2/Mek pathway primarily mediates Nanog gene repression upon ES cell
      differentiation into primitive endoderm.

PMID- 16908535
TI  - Isoform-specific ras activation and oncogene dependence during MYC- and Wnt
      induced mammary tumorigenesis.
AB  - We have previously shown that c-MYC-induced mammary tumorigenesis in mice
      proceeds via a preferred secondary pathway involving spontaneous activating
      mutations in Kras2 (C. M. D'Cruz, E. J. Gunther, R. B. Boxer, J. L. Hartman, L.
      Sintasath, S. E. Moody, J. D. Cox, S. I. Ha, G. K. Belka, A. Golant, R. D.
      Cardiff, and L. A. Chodosh, Nat. Med. 7:235-239, 2001). In contrast, we now
      demonstrate that Wnt1-induced mammary tumorigenesis proceeds via a pathway that
      preferentially activates Hras1. In addition, we find that expression of oncogenic
      forms of Kras2 and Hras1 from their endogenous promoters has markedly different
      consequences for the progression of tumors to oncogene independence. Spontaneous
      activating Kras2 mutations occurring in either MYC- or Wnt1-induced tumors were
      strongly associated with oncogene-independent tumor growth following MYC or Wnt1
      downregulation. In contrast, Hras1-mutant Wnt1-induced tumors consistently
      remained oncogene dependent. Additionally, Kras2-mutant tumors exhibited
      substantially higher levels of ras-GTP, phospho-Erk1/2, and phospho-Mek1/2
      compared to Hras1-mutant tumors, suggesting the involvement of the ras/mitogen
      activated protein kinase (MAPK) pathway in the acquisition of oncogene
      independence. Consistent with this, by use of carcinogen-induced ras mutations as
      well as knock-in mice harboring a latent activated Kras2 allele, we demonstrate
      that Kras2 activation strongly synergizes with both c-MYC and Wnt1 in mammary
      tumorigenesis and promotes the progression of tumors to oncogene independence.
      Together, our findings support a model for tumorigenesis in which c-MYC and Wnt1
      select for the outgrowth of cells harboring mutations in specific ras isoforms
      and that these secondary mutations, in turn, determine the extent of ras/MAPK
      pathway activation and the potential for oncogene-independent growth.

PMID- 16908536
TI  - An hpr1 point mutation that impairs transcription and mRNP biogenesis without
      increasing recombination.
AB  - THO/TREX, a conserved eukaryotic protein complex, is a key player at the
      interface between transcription and mRNP metabolism. The lack of a functional THO
      complex impairs transcription, leads to transcription-dependent
      hyperrecombination, causes mRNA export defects and fast mRNA decay, and retards
      replication fork progression in a transcription-dependent manner. To get more
      insight into the interconnection between mRNP biogenesis and genomic instability,
      we searched for HPR1 mutations that differentially affect gene expression and
      recombination. We isolated mutants that were barely affected in gene expression
      but exhibited a hyperrecombination phenotype. In addition, we isolated a mutant,
      hpr1-101, with a strong defect in transcription, as observed for lacZ, and a
      general defect in mRNA export that did not display a relevant hyperrecombination
      phenotype. In THO single-null mutants, but not in the hpr1 point mutants studied,
      THO and its subunits were unstable. Interestingly, in contrast to
      hyperrecombinant null mutants, hpr1-101 did not cause retardation of replication
      fork progression. Transcription and mRNP biogenesis can therefore be impaired by
      THO/TREX dysfunction without increasing recombination, suggesting that it is
      possible to separate the mechanism(s) responsible for mRNA biogenesis defects
      from the further step of triggering transcription-dependent recombination.

PMID- 16908537
TI  - Conservative repair of a chromosomal double-strand break by single-strand DNA
      through two steps of annealing.
AB  - The repair of chromosomal double-strand breaks (DSBs) is essential to normal cell
      growth, and homologous recombination is a universal process for DSB repair. We
      explored DSB repair mechanisms in the yeast Saccharomyces cerevisiae using single
      strand oligonucleotides with homology to both sides of a DSB. Oligonucleotide
      directed repair occurred exclusively via Rad52- and Rad59-mediated single-strand
      annealing (SSA). Even the SSA domain of human Rad52 provided partial
      complementation for a null rad52 mutation. The repair did not involve Rad51
      driven strand invasion, and moreover the suppression of strand invasion increased
      repair with oligonucleotides. A DSB was shown to activate targeting by
      oligonucleotides homologous to only one side of the break at large distances (at
      least 20 kb) from the break in a strand-biased manner, suggesting extensive 5' to
      3' resection, followed by the restoration of resected DNA to the double-strand
      state. We conclude that long resected chromosomal DSB ends are repaired by a
      single-strand DNA oligonucleotide through two rounds of annealing. The repair by
      single-strand DNA can be conservative and may allow for accurate restoration of
      chromosomal DNAs with closely spaced DSBs.

PMID- 16908538
TI  - The helicase Has1p is required for snoRNA release from pre-rRNA.
AB  - Synthesis of rRNA in eukaryotes involves the action of a large population of
      snoRNA-protein complexes (snoRNPs), which create modified nucleotides and
      participate in cleavage of pre-rRNA. The snoRNPs mediate these functions through
      direct base pairing, in many cases through long complementary sequences. This
      feature suggests that RNA helicases may be involved in the binding and release of
      snoRNPs from pre-rRNA. In this study, we determined that the DEAD box helicase
      Has1p, a nucleolar protein required for the production of 18S rRNA, copurifies
      with the snR30/U17 processing snoRNP but is also present with other snoRNPs.
      Blocking Has1p expression causes a substantial increase in snoRNPs associated
      with 60S-90S preribosomal RNP complexes, including the U3 and U14 processing
      snoRNPs and several modifying snoRNPs examined. Cosedimentation persisted even
      after deproteinization. This effect was not observed with depletion of two
      nonhelicase proteins, Esf1p and Dim2p, that are also required for 18S rRNA
      production. Point mutations in ATPase and helicase motifs of Has1p block U14
      release from pre-rRNA. Surprisingly, depletion of Has1p causes a reduction in the
      level of free U6 snRNP. The results indicate that the Has1p helicase is required
      for snoRNA release from pre-rRNA and production of the U6 snRNP.

PMID- 16908539
TI  - Smoothened signal transduction is promoted by G protein-coupled receptor kinase
      2.
AB  - Deregulation of the Sonic hedgehog pathway has been implicated in an increasing
      number of human cancers. In this pathway, the seven-transmembrane (7TM) signaling
      protein Smoothened regulates cellular proliferation and differentiation through
      activation of the transcription factor Gli. The activity of mammalian Smoothened
      is controlled by three different hedgehog proteins, Indian, Desert, and Sonic
      hedgehog, through their interaction with the Smoothened inhibitor Patched.
      However, the mechanisms of signal transduction from Smoothened are poorly
      understood. We show that a kinase which regulates signaling by many
      "conventional" 7TM G-protein-coupled receptors, G protein-coupled receptor kinase
      2 (GRK2), participates in Smoothened signaling. Expression of GRK2, but not
      catalytically inactive GRK2, synergizes with active Smoothened to mediate Gli
      dependent transcription. Moreover, knockdown of endogenous GRK2 by short hairpin
      RNA (shRNA) significantly reduces signaling in response to the Smoothened agonist
      SAG and also inhibits signaling induced by an oncogenic Smoothened mutant, Smo
      M2. We find that GRK2 promotes the association between active Smoothened and beta
      arrestin 2. Indeed, Gli-dependent signaling, mediated by coexpression of
      Smoothened and GRK2, is diminished by beta-arrestin 2 knockdown with shRNA.
      Together, these data suggest that GRK2 plays a positive role in Smoothened
      signaling, at least in part, through the promotion of an association between beta
      arrestin 2 and Smoothened.

PMID- 16908541
TI  - Increased pancreatic beta-cell proliferation mediated by CREB binding protein
      gene activation.
AB  - The cyclic AMP (cAMP) signaling pathway is central in beta-cell gene expression
      and function. In the nucleus, protein kinase A (PKA) phosphorylates CREB,
      resulting in recruitment of the transcriptional coactivators p300 and CREB
      binding protein (CBP). CBP, but not p300, is phosphorylated at serine 436 in
      response to insulin action. CBP phosphorylation disrupts CREB-CBP interaction and
      thus reduces nuclear cAMP action. To elucidate the importance of the cAMP-PKA
      CREB-CBP pathway in pancreatic beta cells specifically at the nuclear level, we
      have examined mutant mice lacking the insulin-dependent phosphorylation site of
      CBP. In these mice, the CREB-CBP interaction is enhanced in both the absence and
      presence of cAMP stimulation. We found that islet and beta-cell masses were
      increased twofold, while pancreas weights were not different from the weights of
      wild-type littermates. beta-Cell proliferation was increased both in vivo and in
      vitro in isolated islet cultures. Surprisingly, glucose-stimulated insulin
      secretion from perfused, isolated mutant islets was reduced. However, beta-cell
      depolarization with KCl induced similar levels of insulin release from mutant and
      wild-type islets, indicating normal insulin synthesis and storage. In addition,
      transcripts of pgc1a, which disrupts glucose-stimulated insulin secretion, were
      also markedly elevated. In conclusion, sustained activation of CBP-responsive
      genes results in increased beta-cell proliferation. In these beta cells, however,
      glucose-stimulated insulin secretion was diminished, resulting from concomitant
      CREB-CBP-mediated pgc1a gene activation.

PMID- 16908540
TI  - Role of transcription factor NFAT in glucose and insulin homeostasis.
AB  - Compromised immunoregulation contributes to obesity and complications in
      metabolic pathogenesis. Here, we demonstrate that the nuclear factor of activated
      T cell (NFAT) group of transcription factors contributes to glucose and insulin
      homeostasis. Expression of two members of the NFAT family (NFATc2 and NFATc4) is
      induced upon adipogenesis and in obese mice. Mice with the Nfatc2-/- Nfatc4-/-
      compound disruption exhibit defects in fat accumulation and are lean. Nfatc2-/-
      Nfatc4-/- mice are also protected from diet-induced obesity. Ablation of NFATc2
      and NFATc4 increases insulin sensitivity, in part, by sustained activation of the
      insulin signaling pathway. Nfatc2-/- Nfatc4-/- mice also exhibit an altered
      adipokine profile, with reduced resistin and leptin levels. Mechanistically, NFAT
      is recruited to the transcription loci and regulates resistin gene expression
      upon insulin stimulation. Together, these results establish a role for NFAT in
      glucose/insulin homeostasis and expand the repertoire of NFAT function to
      metabolic pathogenesis and adipokine gene transcription.

PMID- 16908542
TI  - PGC-1-related coactivator: immediate early expression and characterization of a
      CREB/NRF-1 binding domain associated with cytochrome c promoter occupancy and
      respiratory growth.
AB  - PGC-1-related coactivator (PRC) was initially characterized as a transcriptional
      coactivator that shares structural and functional features with PGC-1alpha. Both
      coactivators interact with nuclear respiratory factor 1 (NRF-1) and activate NRF
      1 target genes required for respiratory chain expression. Here, we establish that
      PRC belongs to the class of immediate early genes that are rapidly induced in the
      transition from quiescence to proliferative growth. As observed for other members
      of this class, the rapid serum induction of PRC mRNA does not require de novo
      protein synthesis and inhibition of protein synthesis stabilizes PRC mRNA,
      leading to its superinduction. Previous work indicated that PRC activation of
      cytochrome c expression occurs through cis-acting elements that bind both NRF-1
      and CREB. Here, we demonstrate that, like NRF-1, CREB binds PRC in vitro and
      exists in a complex with PRC in cell extracts. Both CREB and NRF-1 bind the same
      sites on PRC, and the interaction with CREB requires the CREB b-Zip DNA binding
      domain. Moreover, a CREB/NRF-1 interaction domain on PRC is required for its
      trans activation of the cytochrome c promoter and a PRC subfragment containing
      this domain inhibits respiratory growth on galactose when expressed in trans from
      a lentivirus vector. Finally, PRC associates with the cytochrome c promoter in
      vivo and its occupancy of the promoter is markedly elevated in response to serum
      induction of quiescent fibroblasts. The results establish that PRC is an
      immediate early gene product that can target key transcription factors as an
      early event in the program of cellular proliferation.

PMID- 16908543
TI  - Sir3 C-terminal domain involvement in the initiation and spreading of
      heterochromatin.
AB  - Heterochromatin is nucleated at a specific site and subsequently spreads into
      distal sequences through multiple interactions between modified histones and
      nonhistone proteins. In the yeast Saccharomyces cerevisiae, these nonhistone
      proteins include Sir2, Sir3, and Sir4. We have previously shown that loss of the
      C-terminal Rap1 domain containing Sir3 and Sir4 association sites can be overcome
      by tethering a 144-amino-acid C-terminal domain (CTD) of Sir3 adjacent to the
      telomere. Here, we explore the substructure and functions of the CTD. We
      demonstrate that the CTD is the minimum domain for Sir3 homodimerization, a
      function that is conserved in related yeasts. However, CTD heterodimers associate
      at only low efficiencies and correspondingly have low levels of tethered
      silencing, consistent with an essential role for dimerization in tethered
      silencing. Six missense alleles were generated, with ctd-Y964A producing the most
      extreme phenotypes when tethered to the LexA binding sites. Although ctd-Y964A is
      capable of dimerization, telomere silencing is abrogated, indicating that the CTD
      serves a second essential function in silencing. Chromatin immunoprecipitation
      analyses of wild-type and ctd-Y964A mutant cells indicate an association of the
      CTD with the deacetylated histone tails of H3 and H4 that is necessary for the
      recruitment of Sir3. The efficiency of spreading depends upon the apparent
      stoichiometry and stability during the initiation event. The predicted Cdc6
      domain III winged-helix structure may well be responsible for dimerization.

PMID- 16908545
TI  - The value of a P value.

PMID- 16908544
TI  - Dynamic interactions between Pit-1 and C/EBPalpha in the pituitary cell nucleus.
AB  - The homeodomain (HD) transcription factors are a structurally conserved family of
      proteins that, through networks of interactions with other nuclear proteins,
      control patterns of gene expression during development. For example, the network
      interactions of the pituitary-specific HD protein Pit-1 control the development
      of anterior pituitary cells and regulate the expression of the hormone products
      in the adult cells. Inactivating mutations in Pit-1 disrupt these processes,
      giving rise to the syndrome of combined pituitary hormone deficiency. Pit-1
      interacts with CCAAT/enhancer-binding protein alpha (C/EBPalpha) to regulate
      prolactin transcription. Here, we used the combination of biochemical analysis
      and live-cell microscopy to show that two different point mutations in Pit-1,
      which disrupted distinct activities, affected the dynamic interactions between
      Pit-1 and C/EBPalpha in different ways. The results showed that the first alpha
      helix of the POU-S domain is critical for the assembly of Pit-1 with C/EBPalpha,
      and they showed that DNA-binding activity conferred by the HD is critical for the
      final intranuclear positioning of the metastable complex. This likely reflects
      more general mechanisms that govern cell-type-specific transcriptional control,
      and the results from the analysis of the point mutations could indicate an
      important link between the mislocalization of transcriptional complexes and
      disease processes.

PMID- 16908546
TI  - Nasal chondrosarcoma in an infant: radiologic and histologic correlation.

PMID- 16908547
TI  - Does vertebroplasty cause incident vertebral fractures? A review of available
      data.
AB  - Vertebroplasty has been in practice in the United States for approximately 10
      years and has been described as providing significant benefit to patients with
      painful vertebral compression fractures. Although the procedure appears to
      provide dramatic pain relief, it is not without complications. The primary point
      of discussion in this paper is whether vertebroplasty predisposes patients to the
      development of additional vertebral fractures, at a rate higher than that seen in
      the absence of vertebroplasty. To date there remains no definitive answer to this
      question. There is, however, a significant body of data available in the
      literature that relates to this issue. This review explores and attempts to
      synthesize the data both supporting and refuting a relationship between
      vertebroplasty and the development of subsequent fractures.

PMID- 16908548
TI  - A systematic literature review of magnetic resonance spectroscopy for the
      characterization of brain tumors.
AB  - BACKGROUND AND PURPOSE: Proton MR spectroscopy ((1)H-MR spectroscopy) is a
      potentially useful adjunct to anatomic MR imaging in the characterization of
      brain tumors. We performed an updated systematic review of the evidence. METHODS:
      We employed a standardized search strategy to find studies published during 2002
      2004. We reviewed studies measuring diagnostic accuracy and diagnostic,
      therapeutic, or health impact of (1)H-MR spectroscopy. We abstracted information
      on study design, (1)H-MR spectroscopy technique, and methodologic quality. We
      categorized studies into 5 subgroups: (1) metastasis versus high-grade tumor; (2)
      high-versus low-grade tumor; (3) recurrent tumor versus radiation necrosis; (4)
      tumor extent; and (5) tumor versus non-neoplastic lesion. RESULTS: We identified
      26 studies evaluating diagnostic performance, diagnostic impact, or therapeutic
      impact. No articles evaluated patient health or cost-effectiveness. Methodologic
      quality was mixed; most used histopathology as the reference standard but did not
      specify blinded interpretation of histopathology. One large study demonstrated a
      statistically significant increase in diagnostic accuracy for indeterminate brain
      lesions from 55%, based on MR imaging, to 71% after analysis of (1)H-MR
      spectroscopy. Several studies have found that (1)H-MR spectroscopy is highly
      accurate for distinguishing high- and low-grade gliomas, though the incremental
      benefit of (1)H-MR spectroscopy in this setting is less clear. Interpretation for
      the other clinical subgroups is limited by the small number of studies.
      CONCLUSION: The current evidence on the accuracy of (1)H-MR spectroscopy in the
      characterization of brain tumors is promising. However, additional high-quality
      studies are needed to convince policy makers. We present guidelines to help focus
      future research in this area.

PMID- 16908549
TI  - 3T 1H-MR spectroscopy in grading of cerebral gliomas: comparison of short and
      intermediate echo time sequences.
AB  - BACKGROUND AND PURPOSE: Echo time (TE) can have a large influence on the spectra
      in proton MR spectroscopy ((1)H-MR spectroscopy). The purpose of this study was
      to comparatively assess the diagnostic value of 3T single-voxel (1)H-MR
      spectroscopy with short or intermediate TEs in grading cerebral gliomas. METHODS:
      Single voxel (1)H-MR spectroscopy was performed at 3T in 35 patients with
      cerebral glioma. The spectra were obtained with both short (35 ms) and
      intermediate TEs (144 ms). Metabolite ratios of choline (Cho)/creatine (Cr),
      Cho/N-acetylaspartate (NAA), lipid and lactate (LL)/Cr and myo-inositol (mIns)/Cr
      were calculated and compared between short and intermediate TEs in each grade.
      After receiver operating characteristic curve analysis, diagnostic accuracy for
      each TE in differentiating high-grade glioma from low-grade glioma was compared.
      RESULTS: At short TE, Cho/Cr and Cho/NAA ratios were significantly lower, and
      LL/Cr and mIns/Cr were significantly higher, compared with those at intermediate
      TE, regardless of tumor grade. Lactate inversion at intermediate TE was found in
      only 2 patients. At both TEs, there were significant differences in Cho/Cr and
      LL/Cr ratios between low- and high-grade gliomas. Diagnostic accuracy was
      slightly higher at short TE alone or combined with intermediate TE than
      intermediate TE alone (85.7% versus 82.9%). CONCLUSION: Metabolite ratios were
      significantly different between short and intermediate TE. Cho/Cr and LL/Cr
      ratios at either TE were similarly useful in differentiating high-grade gliomas
      from low-grade gliomas. If only a single spectroscopic sequence can be acquired,
      short TE seems preferable because of poor lactate inversion at intermediate TE on
      3T single-voxel (1)H-MR spectroscopy.

PMID- 16908550
TI  - Diffusion-weighted imaging of metastatic brain tumors: comparison with histologic
      type and tumor cellularity.
AB  - BACKGROUND AND PURPOSE: On diffusion-weighted imaging (DWI), metastatic tumors of
      the brain may exhibit different signal intensities (SI) depending on their
      histology and cellularity. The purpose of our study was to verify the hypotheses
      (1) that SI on DWI predict the histology of metastases and (2) that apparent
      diffusion coefficient (ADC) values reflect tumor cellularity. MATERIALS AND
      METHODS: We assessed conventional MR images, DWI, and ADC maps of 26 metastatic
      brain lesions from 26 patients, 13 of whom underwent surgery after the MR
      examination. Two radiologists performed qualitative assessment by consensus of
      the SI on DWI in areas corresponding to their enhancing portions. We measured the
      contrast-to-noise ratio (CNR) on T2-weighted images and normalized ADC (nADC)
      values, and compared them with tumor cellularity. RESULTS: The mean SI on DWI and
      the CNR on T2-weighted images were significantly lower in well differentiated
      than in poorly differentiated adenocarcinomas and lesions other than
      adenocarcinoma. The mean nADC value was significantly higher in well
      differentiated than poorly differentiated adenocarcinomas and lesions other than
      adenocarcinoma. All 3 small-cell carcinomas and 1 large-cell neuroendocrine
      carcinoma exhibited high SI on DWI. The nADC value showed a significant inverse
      correlation with tumor cellularity. There was no significant correlation between
      the CNR and tumor cellularity. CONCLUSION: The SI on DWI may predict the
      histology of metastases; well differentiated adenocarcinomas tended to be
      hypointense, and small- and large-cell neuroendocrine carcinomas showed
      hyperintensity. Their ADC values reflect tumor cellularity.

PMID- 16908551
TI  - Disarrangement of fiber tracts and decline of neuronal density correlate in
      glioma patients--a combined diffusion tensor imaging and 1H-MR spectroscopy
      study.
AB  - BACKGROUND AND PURPOSE: Diffusion tensor imaging (DTI) and MR spectroscopy are
      noninvasive, quantitative tools for the preoperative assessment of gliomas with
      which the quantitative parameter fractional anisotropy (FA) and the concentration
      of neurometabolites N-acetylaspartate (NAA), choline (Cho), creatine (Cr) of the
      brain can be determined. Measurements of FA and NAA reflect the integrity of
      fiber tracts and the presence of neurons, respectively. This investigation
      examines changes of FA and NAA and compares these different aspects in
      architecture of gliomas after spatial coregistration. METHODS: DTI and chemical
      shift (1)H-MR spectroscopy was performed in 34 healthy volunteers and 69 patients
      with histologically confirmed (n = 48) or morphologically suspected (n = 21) non
      necrotic brain glioma. Volumes of interest (VOIs) were placed in the tumor center
      (TC), the tumor border (TB), the normal-appearing white matter adjacent to the
      tumors (TNWM), and in the white matter of the contralateral hemisphere (NWMC).
      Median FA values and NAA/Cr and NAA/Cho ratios were calculated in the patients'
      VOIs and the gray and white matter of the volunteers. Correlations of FA values
      and NAA ratios were calculated. RESULTS: Continuous changes of FA and NAA from
      the tumor center to the periphery (the adjacent white matter and the contra
      lateral hemisphere, respectively) were observed, where median values were: TC:
      0.73 +/- 0.45, 0.47 +/- 0.58, 0.17 +/- 0.15 (NAA/Cr, NAA/Cho, FA); TB: 1.06 +/-
      0.53, 1.00 +/- 0.15, 0.23 +/- 0.08; TNWM: 1.42 +/- 2.48, 1.21 +/- 0.95, 0.34 +/-
      0.09; and NWMC: 1.63 +/- 0.72, 1.56 +/- 1.34, 0.38 +/- 0.08. Correlation of
      median FA values and NAA ratios in the cumulative group of patients was high (r =
      0.99 [NAA/Cr], 0.95 [NAA/ Cho] at P < .01). Correlation between the individual
      NAA ratios and the FA values was moderate (r = 0.53 [NAA/Cr], 0.51 [NAA/Cho] at P
      < .01). CONCLUSION: In gliomas, the degree of tissue organization decreases
      continuously from the surrounding tissue toward the center of the tumor
      accompanied by a concordant decrease of NAA. This uniform behavior of FA and NAA
      reflects a decreasing integrity of both neuronal structures and fibers.

PMID- 16908552
TI  - [11C]methionine PET, histopathology, and survival in primary brain tumors and
      recurrence.
AB  - BACKGROUND AND PURPOSE: [(11)C]Methionine (MET) PET imaging is a sensitive
      technique for visualizing primary brain tumors and recurrence/progression after
      therapy. The aim of this study was to evaluate the relationship between the
      uptake of MET and histopathologic grading and to investigate the prognostic value
      of the tracer, in both settings. METHODS: Cerebral uptake of MET was determined
      in 52 patients: in 26 patients for primary staging (group A) and 26 patients with
      suspected brain tumor recurrence/progression after therapy (group B).
      Semiquantitative methionine uptake indices (UI) defined by the tumor (maximum)-to
      background ratio was correlated with tumor grade and final outcome. RESULTS:
      Overall median survival was 34.9 months. MET showed pathologically increased
      uptake in 41 of 52 scans. Although a weak linear correlation between MET uptake
      and grading was observed (R = 0.38, P = .028), analysis of variance showed no
      significant differences in MET UI between tumor grades for either group A or B.
      Benign and grade I lesions showed significant difference in MET uptake in
      comparison with higher grade lesions (P = .006). Using Kaplan-Meier survival
      analysis, no thresholds could be found at which MET was predictive for survival.
      Proportional hazard regression showed that only WHO grading class (low versus
      high) was predictive of survival (P = .015). CONCLUSION: Interindividual MET
      uptake variability does not allow noninvasive grading on an individual patient
      basis. Moreover, there is no significant prognostic value in studying maximal
      methionine UI in brain tumors. The clinical use of MET should therefore be
      primarily focused on questions such as detection of recurrence, biopsy guidance,
      and radiation therapy target volume delineation.

PMID- 16908553
TI  - MR spectroscopy-aided differentiation: "giant" extra-axial tuberculoma
      masquerading as meningioma.
AB  - Tuberculosis is common in the developing world and in developed nations secondary
      to increasing immunocompromise in the population. It commonly causes meningitis
      and parenchymal tuberculomas. We present a case of an unusual masslike "giant"
      extra-axial tuberculoma during pregnancy. Unusual morphology and size at imaging
      made meningioma a close differential. MR spectroscopy served to complement MR
      imaging, providing diagnostic confirmation and depicted findings characteristic
      of a tuberculoma.

PMID- 16908554
TI  - Trading spectral separation at 3T for acquisition speed in multi spin-echo
      spectroscopic imaging.
AB  - Fast multiple spin-echo spectroscopic imaging, also called turbo spectroscopic
      imaging (TSI), may be enhanced in terms of acquisition speed by taking advantage
      of the higher spectral separation afforded at higher field strength and by
      further combining it with sensitivity encoding (SENSE). This article demonstrates
      the possibilities of this approach at 3T, resulting in scan-time reductions of up
      to a factor of 10. High-resolution, in vivo, single- and multiple-section
      spectroscopic imaging data are presented.

PMID- 16908555
TI  - Multiple reversible MR signal changes caused by Epstein-Barr virus encephalitis.
AB  - This report presents the imaging findings of an unusual case of Epstein-Barr
      virus (EBV) encephalitis. A young man presented with a short-lasting history of
      febrile infection, neuropsychologic deficits, ataxia, and seizures. MR imaging
      revealed fully reversible signal intensities (T2, diffusion-weighted imaging with
      a decreased apparent diffusion coefficient) in the splenium of the corpus
      callosum and both posterior hemispheres. EBV infection must be added to the list
      of differential diagnoses of (reversible) splenial lesions.

PMID- 16908556
TI  - Differential cortical thickness across the central sulcus: a method for
      identifying the central sulcus in the presence of mass effect and vasogenic
      edema.
AB  - BACKGROUND AND PURPOSE: Identification of the motor strip on MR imaging studies
      is difficult in the presence of mass effect and vasogenic edema because sulcal
      landmarks are obscured. We hypothesize that a difference in cortical thickness
      between the motor and sensory strips is readily apparent on T2-weighted images in
      the presence of vasogenic edema and reliably identifies the central sulcus.
      METHODS: Thirteen patients with brain tumors resulting in vasogenic edema near
      the central sulcus were identified. The cortical thickness of the anterior and
      posterior banks of the central sulcus as well as the neighboring sulci in the
      frontal and parietal lobes were measured from T2-weighted images. Similar
      measures were obtained from neighboring sulci in the frontal and parietal lobes.
      Location of the central sulcus was confirmed with standard anatomic landmarks in
      all patients and by intraoperative cortical mapping in 2 patients. RESULTS: A
      twofold difference in cortical thickness between the anterior and posterior banks
      of the central sulcus uniquely identified the central sulcus on T2-weighted
      images in the presence of vasogenic edema, despite the marked distortion of
      sulcal anatomy as a result of mass effect. This relationship was not present in
      neighboring sulci. CONCLUSION: Cytoarchitectonic differences in the motor and
      sensory cortices result in a markedly thicker posterior than anterior bank of the
      central sulcus that is readily visible on routine T2-weighted images in the
      presence of vasogenic edema. Therefore, the cortical thickness can serve as a
      complementary method in identification of the motor strip in patients with mass
      effect.

PMID- 16908557
TI  - Temporal horn index and volume of medial temporal lobe atrophy using a new
      semiautomated method for rapid and precise assessment.
AB  - BACKGROUND AND PURPOSE: Quantitative markers of Alzheimer disease (AD),
      particularly in the early stages, are needed for clinical assessment and
      monitoring. We have evaluated a novel method to segment and visualize the
      ventricular system and obtain volumetric measures thereof. The temporal horn
      volume (THV) and index in patients with mild cognitive impairment (MCI) and in
      those with AD were evaluated. METHODS: High-resolution T1-weighted volume imaging
      was performed in 52 subjects (21 patients with MCI, 10 with AD, and 21 healthy
      control subjects). An interactive watershed transformation and semiautomated
      histogram analysis were implemented to produce segmented THV and temporal horn
      indices (THI) (ratio of THV to lateral ventricular volume). RESULTS: Cerebral
      ventricular and temporal horn size could be semiautomatically quantified from all
      52 datasets. The method was fast and rater-independent. Qualitative ventricular
      inspections using surface rendering shading could uncover atrophic process with
      enlargement of the whole and especially temporal horn volume. Both THV and THI of
      patients with AD were significantly larger than those of patients with MCI or
      control subjects (P < .005). There was no significant difference in THV and THI
      between patients with MCI or control subjects (P > .05). There was a significant
      correlation between the neuropsychologic performance and both THI and THV across
      groups (P < .01). CONCLUSION: THV and THI could be used as markers of AD in the
      clinical environment and are expected to be helpful in monitoring therapeutic
      intervention.

PMID- 16908558
TI  - Creutzfeldt-Jakob disease: comparative analysis of MR imaging sequences.
AB  - BACKGROUND AND PURPOSE: MR imaging has played an increasingly important role in
      the diagnosis of Creutzfeldt-Jakob disease (CJD) since basal ganglia
      abnormalities on T2-weighted images have been described; thus, the aim of our
      study was to compare the value of different MR images in the diagnosis of CJD.
      METHODS: One hundred fifty-seven patients with CJD underwent MR imaging
      examinations. Ninety-two patients were neuropathologically confirmed, and 65 were
      clinically classified as having CJD through the CJD Surveillance Unit
      (probability of 95%). There was no standardized MR imaging protocol; thus, the
      examinations included 143 T2-weighted, 43 proton attenuation (PD)-weighted, 84
      fluid-attenuated inversion recovery (FLAIR), and 44 diffusion-weighted images
      (DWI). The MR images were reviewed for pathologic changes of the basal ganglia,
      thalamus, and cerebral cortex. RESULTS: Cortical abnormalities were present in 70
      patients (45%) and were visible in 80% (35/44) of all available DWI examinations.
      The basal ganglia were affected in 94 patients (60%), in particular in the
      caudate nucleus; the most sensitive sequences were DWI (64%) and PD-weighted
      (63%). A thalamic involvement was more frequently diagnosed on PD-weighted images
      (19%) and DWI (14%) than on FLAIR or T2-weighted images. CONCLUSION: PD-weighted
      images and DWI showed better results in the diagnosis of signal intensity changes
      in the basal ganglia compared with T2-weighted or FLAIR images; however, in the
      diagnosis of cortical changes, DWI was clearly superior. Our data suggest that
      DWI is the most sensitive MR imaging technique in the diagnosis of CJD.

PMID- 16908559
TI  - Global and region-specific analyses of apparent diffusion coefficient in
      dentatorubral-pallidoluysian atrophy.
AB  - BACKGROUND AND PURPOSE: Dentatorubral-pallidoluysian atrophy (DRPLA) is an
      autosomal dominant spinocerebellar ataxia. Techniques for the quantitative
      assessment of neurodegenerative lesions remain to be established in this disease.
      We attempted to quantify global and region-specific neurodegeneration in DRPLA
      using analysis of apparent diffusion coefficient (ADC) maps. METHODS: Diffusion
      weighted images (b = 1000 s/mm(2)) by echo-planar sequences were obtained with
      the use of a 1.5T clinical scanner. Whole-brain histogram and region of interest
      (ROI) analyses of ADC values as well as conventional MR imaging studies were
      performed in 6 patients with genetically confirmed DRPLA. RESULTS: Histograms
      demonstrated significantly higher mean ADC values in the patients than in age-
      and sex-matched control subjects (P < .01). ROI analysis revealed that the
      patients had significantly higher ADC values in the cerebellum and globus
      pallidus, preferentially affected regions (P < .05), but not in the thalamus, the
      region relatively spared in this disease. ADC values in the white matter were
      higher only in patients with adult-onset disease. Histogram analyses could more
      sensitively identify abnormalities than ROI analyses, because the former avoided
      errors associated with setting ROIs and thus had smaller P values on statistical
      analysis than the latter. CONCLUSIONS: Histogram ADC analyses were more sensitive
      for the detection of neurodegeneration in DRPLA than ROI analyses, whereas ROI
      analyses revealed regional alterations reflecting the distribution of pathologic
      changes. Thus, histogram and ROI analyses complement each other and may permit
      the sensitive, quantitative evaluation of neurodegeneration in DRPLA, especially
      that involving the globus pallidus showing normal T2 signals.

PMID- 16908560
TI  - Functional brain imaging using a long intravenous half-life gadolinium-based
      contrast agent.
AB  - PURPOSE: We describe a technique for functional MR imaging (fMRI) with high
      spatial and temporal resolution using a long intravascular half-life gadolinium
      based contrast agent, MS-325. METHODS: All fMRI measurements used a rat model of
      sensory cortex activation with forepaw electrical stimulation under alpha
      chloralose anesthesia. Standard blood oxygen level-dependent (BOLD) fMRI
      measurement was initially performed. MS-325 was then intravenously administered
      and a MS-325 fMRI measurement was performed by using a 3D gradient-echo sequence.
      RESULTS: We found that a dose of 0.1 mmol/kg MS-325 produced adequate signal
      intensity changes in rat sensory cortex to demonstrate activations. Using a
      boxcar stimulation pattern with a standard correlation analysis, the locations of
      the most significantly activated voxels (ie, highest Z score) in the MS-325 and
      BOLD fMRI measurements were not significantly different. CONCLUSIONS: MS-325 fMRI
      has the advantage of using a T1-weighted sequence, rather than the highly T2*
      weighted sequences used in other common fMRI techniques. This could reduce the
      susceptibility artifacts associated with fMRI.

PMID- 16908561
TI  - A functional MRI study: cerebral laterality for lexical-semantic processing and
      human voice perception.
AB  - BACKGROUND AND PURPOSE: Language dominance research using functional neuroimaging
      has made important contributions to clinical applications. Nevertheless, although
      recent neuroimaging studies demonstrated right-lateralized activation by human
      voice perception, the influence of voice perception in terms of language
      dominance has not been adequately studied. We aimed to accurately clarify
      language dominance for lexical-semantic processing in the temporal cortices by
      focusing on human voice perception. METHODS: Thirty normal right-handed subjects
      were scanned by functional MR imaging while listening to sentences (SEN), reverse
      sentences (rSEN), and identifiable nonvocal sounds (SND). We investigated
      cerebral activation and the distribution of individual Laterality Index under 3
      contrasts: rSEN-SND, SEN-SND, and SEN-rSEN. RESULTS: The rSEN-SND contrast,
      including human voice perception, revealed right-lateralized activation in the
      anterior temporal cortices. Both SEN-SND and SEN-rSEN contrasts, including
      lexical-semantic processing, showed left-lateralized activation in the inferior
      and middle frontal gyrus and middle temporal gyrus. The SEN-rSEN contrast,
      without the influence of human voice perception, showed no temporal activation in
      the right hemisphere. Symmetrical or right-lateralized activation was observed in
      22 of 27 subjects (81.4%) under the rSEN-SND contrast in the temporal cortices.
      Although 9 of 27 subjects (33.3%) showed symmetrical or right-lateralized
      activation under the SEN-SND contrast in the temporal cortices, all subjects
      showed left-lateralized activation under the SEN-rSEN contrast. CONCLUSION: Our
      results demonstrated that right-lateralized activation by human voice perception
      could mask left-lateralized activation by lexical-semantic processing. This
      finding suggests that the influence of human voice perception should be
      adequately taken into account when language dominance is determined.

PMID- 16908562
TI  - Single-shot, turbo spin-echo, diffusion-weighted imaging versus spin-echo-planar,
      diffusion-weighted imaging in the detection of acquired middle ear cholesteatoma.
AB  - Diagnosis of acquired middle ear cholesteatoma on MR imaging is mostly done on
      late postgadolinium T1-weighted MR images and/or echo-planar (EPI) diffusion
      weighted (DWI) MR images. We describe the appearance of a case of a complicated
      attical middle ear cholesteatoma on single-shot (SS) turbo spin-echo (TSE) DWI
      compared with EPI-DWI. This case suggests a higher reliability of SS TSE-DWI in
      the diagnosis of acquired middle ear cholesteatoma.

PMID- 16908563
TI  - CNS metastases of carcinoma ex pleomorphic adenoma of the parotid gland.
AB  - Pleomorphic adenomas (PAs), also known as benign mixed tumors, are common tumors
      of the parotid gland. These tumors occasionally undergo malignant transformation,
      with potentially devastating consequences. This case report presents the clinical
      and radiographic features of a rare case of biopsy proved brain and spinal cord
      metastases arising from carcinoma ex PA of the parotid gland.

PMID- 16908564
TI  - The cochlear-carotid interval: anatomic variation and potential clinical
      implications.
AB  - BACKGROUND AND PURPOSE: A temporal bone CT study in a patient with episodic mid
      tone sensorineural hearing loss and tinnitus demonstrated absence of bone between
      the petrous internal carotid artery and the basal turn of the cochlea. The
      potential implications with respect to increasingly popular cochlear implant
      surgery compelled us to retrospectively analyze a series of temporal bone CT
      scans to establish typical measurements for this region, which we termed the
      "cochlear-carotid interval" (CCI). METHODS: After IRB exemption, 2 observers
      independently measured the bony interval between the cochlea and the petrous
      internal carotid artery canal on coronal images from 30 consecutive temporal bone
      CT studies. The 1-mm thick coronal images were either acquired directly or were
      reconstructed from an axial dataset acquired at 0.75 or 0.6 mm section thickness.
      All measurements were performed by using electronic calipers on a Sienet
      MagicView VE 42 Siemens PACS station. Mixed model analysis of variance was used
      to evaluate differences between readers and sides with respect to the mean CCI
      but adjusted for age and accommodating the correlation among observations
      generated for the same subject. RESULTS: The patient in our case report had a
      right CCI of 0.2 mm and left CCI of 0.0 mm. In the other 30 patients, the right
      CCI ranged from 0.2 to 3.8 mm (mean, 1.2 +/- 0.8 mm; median, 0.9) and the left
      CCI from 0.2 to 5.0 mm (mean, 1.1 +/- 0.9 mm; median, 0.8). The CCI did not
      exhibit a significant association with subject age (P = .1336), and there were no
      significant differences between readers (P = .824) or sides (P = .350) in terms
      of mean CCI. CONCLUSION: The CCI varies widely between patients and may be as
      small as zero. Analysis of anatomic relationships suggests a potential
      relationship between small CCI and mid-tone sensorineural hearing loss, as in our
      reported patient. Preoperative knowledge of thin or absent bone between the
      cochlea and petrous carotid canal may help prevent inadvertent penetration of the
      carotid canal during cochlear implant surgery.

PMID- 16908565
TI  - Incidental giant arachnoid granulation.
AB  - Arachnoid granulations may expand the dural sinuses or inner table of the skull.
      Although usually incidental, giant arachnoid granulations that are of sufficient
      size to fill the lumen of a dural sinus and cause local dilation or filling
      defects can rarely cause symptoms due to sinus obstruction leading to venous
      hypertension. This 31-year-old man presented with a 3-month history of
      progressive bifrontal headaches and a giant arachnoid granulation at the
      posterior superior sagittal sinus. Intrasinus pressure measurements showed no
      significant pressure difference across the lesion to explain the headaches, which
      were then treated medically. Dural sinus pressure measurement, in certain cases
      of giant arachnoid granulations, can be used to exclude the lesion as the cause
      of the patient's symptoms.

PMID- 16908566
TI  - Clinical relevance of musical murmurs in color-coded carotid and transcranial
      duplex sonographies.
AB  - BACKGROUND AND PURPOSE: Musical murmurs (MMs), sometimes called seagull cry,
      goose cry, honks, or cooing murmur, are murmurs with a single frequency that
      sounds like a musical tone. Doppler detections usually show mirror-image parallel
      strings or bands of low to moderate frequency. Musical murmurs are mostly
      described in cardiac murmurs and have seldom been mentioned in cerebrovascular
      disease. METHODS: A retrospective review of 12,000 patients from our
      neurosonographic data base of the past 7 years was conducted to find patients who
      had MMs during color-coded carotid and transcranial duplex sonographies. RESULTS:
      Sixty-six musical murmurs were found in 60 patients (0.5% of all studied
      patients). There were 44 men and 16 women with a mean age of 63.8 years. Musical
      murmurs may occur with or without simultaneous turbulent flows, or very close to
      a high-intensity frequency (with systolic spindles) turbulent flow. Musical
      murmurs are detected more frequently in intracranial vessels (94%) than in
      extracranial cervical arteries. The pathologic changes corresponding to the area
      of MMs were high-grade stenosis of the arteries (58 MMs), small arteries serving
      as collateral circulation (5 MMs), carotid cavernous sinus fistulas (2 MMs), and
      Moyamoya disease (1 MM). Fifty (88%) of 57 patients with stenotic arterial
      lesions had histories of cerebral infarction or transient ischemic attack, and
      64% of the cerebrovascular events occurred on the side appropriate to the MMs.
      CONCLUSIONS: The presence of MMs in color-coded carotid duplex and transcranial
      color-coded duplex sonography imply severe underlying vascular diseases that
      require prompt treatment. Further cerebral angiographic study is warranted to
      clarify the underlying pathology in patients with MMs.

PMID- 16908567
TI  - Procedural complications of coiling of ruptured intracranial aneurysms: incidence
      and risk factors in a consecutive series of 681 patients.
AB  - BACKGROUND AND PURPOSE: To report the incidence of procedural complications of
      coiling of ruptured intracranial aneurysms leading to permanent disability or
      death in a consecutive series of 681 patients and to identify risk factors for
      these events. PATIENTS AND METHODS: Between January 1995 and July 2005, 681
      consecutive patients with ruptured intracranial aneurysms were treated with
      detachable coils. Procedural complications (aneurysm rupture or thromboembolic)
      of coiling leading to death or neurologic disability at the time of hospital
      discharge were recorded. For patients with procedural complications, odds ratios
      (OR) with corresponding 95% confidence intervals (CI) were calculated for the
      following patient and aneurysm characteristics: patient age and sex, use of a
      supporting balloon, aneurysm location, timing of treatment, clinical condition at
      the time of treatment, and aneurysm size. RESULTS: Procedural complications
      occurred in 40 of 681 patients (5.87%; 95% CI, 4.2% to 7.9%), leading to death in
      18 patients (procedural mortality, 2.6%; 95% CI, 1.6% to 4.2%) and to disability
      in 22 patients (procedural morbidity, 3.2%; 95% CI, 2.0% to 4.9%). There were 8
      procedural ruptures and 32 thromboembolic complications. The use of a temporary
      supporting balloon was the only significant risk factor (OR, 5.1; 95% CI, 2.3 to
      15.3%) for the occurrence of procedural complications. CONCLUSION: Procedural
      complication rate of coiling of ruptured aneurysms leading to disability or death
      is 5.9%. In this series, the use of a temporary supporting balloon in the
      treatment of wide-necked aneurysms was the only risk factor for the occurrence of
      complications.

PMID- 16908568
TI  - Direct carotid puncture for the endovascular treatment of anterior circulation
      aneurysms.
AB  - We report the usefulness of Guglielmi detachable coil (GDC) embolization by
      direct carotid puncture for anterior circulation aneurysms. For all 27 patients,
      GDC embolization by direct carotid puncture was safely performed by using a 5F
      sheath introducer 5 cm long and a Tracker-38 catheter. Neurologic deficits and
      hemorrhage were not found in any patient during the follow-up period. If the
      transfemoral approach cannot be applied, GDC embolization should be considered as
      an alternative method.

PMID- 16908569
TI  - The significance of incomplete stent apposition in patients undergoing stenting
      of internal carotid artery stenosis.
AB  - BACKGROUND AND PURPOSE: Incomplete stent apposition after carotid angioplasty and
      stent placement (CAS) is often seen but little is known about how the incomplete
      attachment goes after stent placement. For example, some may change into
      restenosis around the stent edge and some may remain unchanged. The purpose of
      this study is to clarify the morphologic prognosis of an incomplete stent
      apposition at the stent edge. METHODS: CAS was attempted on 135 consecutive
      stenotic lesions (124 patients). Angiograms were then evaluated immediately after
      the procedure. An incomplete stent apposition at stent edge was found in 15
      patients, and all of them were followed up by angiography and MR imaging with
      antiplatelet therapy. RESULTS: No ischemic event caused by the lesions occurred
      during the mean follow-up period of 11 months (from 4 to 32 months). The
      angiography findings of 15 lesions at a mean of 8.8 months (from 2 to 28 months)
      after CAS showed that all remained unchanged. No patients required any additional
      intervention. No new ischemic lesions were detected in any of the 15 patients who
      underwent follow-up MR imaging at a mean of 10 months (from 2 to 32 months) after
      CAS. CONCLUSION: In this study, the existence of a segment of incomplete stent
      apposition had no adverse morphologic or clinical effect.

PMID- 16908570
TI  - Hyperacute intracerebral hemorrhage complicating carotid stenting should be
      distinguished from hyperperfusion syndrome.
AB  - We describe a patient who experienced a fatal ipsilateral basal ganglia
      hemorrhage within an hour after carotid angioplasty and stent placement. In the
      few similar cases published there were no prodromata, but hyperacute onset of
      severe neurologic deterioration corresponding to intracerebral hemorrhage (ICH).
      Our findings suggest that besides the delayed ICH that is associated with
      hyperperfusion syndrome (HPS), a second type of hyperacute and usually fatal ICH
      exists that resembles hypertensive hemorrhage.

PMID- 16908571
TI  - Endovascular treatment of intracranial vertebral artery dissections with stent
      placement or stent-assisted coiling.
AB  - BACKGROUND AND PURPOSE: Endovascular treatment with stent placement or stent
      assisted coiling was recently introduced as an alternative to parent artery
      occlusion in intracranial vertebral artery dissections. We describe the efficacy
      and limitations of this method. METHODS: Fourteen patients with intracranial
      vertebral artery dissection were treated with stent placement (10 patients) or
      stent-assisted coiling (4 patients). Double overlapping stents were deployed in 4
      of 10 patients with stent placement alone. Angiographic follow-up at 6 to 12
      months was available in 13 patients. RESULTS: In 13 patients with dissecting
      aneurysm, immediate angiographic outcomes were complete occlusion (1 patient),
      nearly complete (2 patients), and incomplete (10 patients). Follow-up angiograms
      of 12 of these patients showed complete occlusion (6 patients) and incomplete (6
      patients; 1 unstable and 5 stable). Complete occlusion rates in follow-up
      angiograms were superior in double stent placement (75%) or stent-assisted
      Guglielmi detachable coil (GDC) embolization to stent placement alone (0%). There
      were no instances of postprocedural ischemic attacks, new neurologic deficits,
      and no new minor or major strokes before patient discharge. On the modified
      Rankin scale applied in follow-up, all patients were assessed as functionally
      improved or of stable clinical status. CONCLUSIONS: Intracranial vertebral artery
      dissections were acceptably treated with stent placement or stent-assisted
      coiling, and the patency could be preserved at follow-up. However, the efficiency
      of stent placement alone for intracranial vertebral artery dissecting aneurysm
      was limited. Stent-assisted coil embolization or double stent placements are a
      viable alternative for complete occlusion of dissecting aneurysms.

PMID- 16908572
TI  - Clot removal therapy by aspiration and extraction for acute embolic carotid
      occlusion.
AB  - BACKGROUND AND PURPOSE: The purpose of our retrospective study was to investigate
      the feasibility, safety, and efficacy of clot removal therapy by aspiration and
      extraction for patients with acute stroke with embolic internal carotid artery
      (ICA) occlusion. METHODS: Of 814 consecutive patients with acute ischemic stroke
      admitted to our institution from March 2003 to April 2005, clot removal therapy
      was performed for 14. Inclusion criteria were patients (1) presenting within 6
      hours of onset of cardioembolic stroke, (2) with serious neurologic symptoms
      defined by a National Institutes of Health Stroke Scale (NIHSS) score of at least
      11, (3) without extensive high signal intensity on diffusion-weighted MR images
      but with decreased ipsilateral hemispheric cerebral blood flow on perfusion
      weighted images (perfusion/diffusion mismatch), and (4) with total ICA occlusion
      on angiograms. We removed clots by aspiration and extraction with a microsnare
      through either a guiding or balloon guide catheter. Radiographic results, 7-day
      NIHSS, 3-month modified Rankin Scale, and procedure-related complications were
      evaluated. RESULTS: Of 10 patients treated with the balloon guide catheter to
      temporarily interrupt proximal flow, 7 obtained complete or partial
      recanalization. The 4 patients treated with the guiding catheter had no
      recanalization. Of the 7 patients with recanalization, 6 had favorable 7-day
      neurologic and 3-month functional outcome; all showed anatomic crossflow via the
      anterior communicating artery. A procedure-related complication, distal
      embolization into the ipsilateral anterior cerebral artery, occurred in 1
      patient. CONCLUSION: Balloon guide catheter-assisted clot removal therapy for
      embolic ICA occlusion may provide a high recanalization rate and good clinical
      outcome in patients with anatomic crossflow.

PMID- 16908573
TI  - Arteriographic demonstration of slow antegrade opacification distal to a
      cerebrovascular thromboembolic occlusion site as a favorable indicator for intra
      arterial thrombolysis.
AB  - PURPOSE: This study sought to determine whether the angiographic demonstration of
      slow antegrade contrast opacification of an occluded cerebral artery distal to
      the thrombus (clot outline sign) on cerebral arteriograms performed immediately
      before thrombolytic treatment is associated with higher recanalization rates
      relative to patients without antegrade contrast opacification distal to the
      occlusion site. METHODS: The angiographic images of 100 consecutive arteriograms
      performed before thrombolysis in patients eligible for intra-arterial
      thrombolysis from May 1995 to February 2005 were reviewed. A modified
      Thrombolysis in Myocardial Infarction flow grade (mTIMI) was adapted to grade
      recanalization after cerebral thrombolysis. Clot outline sign was defined as slow
      antegrade contrast opacification distal to the thrombus on the delayed images of
      the presenting arteriogram. Logistic regression analysis for mTIMI grade included
      the following potential predictors: presence of outline sign, age, time to
      treatment, sex, site of occlusion, presenting National Institutes of Health
      Stroke Scale (NIHSS) score, presenting platelets, presenting systolic blood
      pressure, presence of pial collaterals, and admitting glucose value. RESULTS:
      Eighty-seven arteriograms were reviewed. Of these, 19 (22%) displayed the clot
      outline sign. Thirteen (69%) of 19 had clot outline sign, and 16 of 68 (29%) were
      not completely recanalized (mTIMI = 3); 95% with clot outline sign and 54%
      without were associated with either mTIMI 2 or 3 (P = .0055, Pearson
      correlation). Logistic regression analysis for recanalization relative to other
      predictors indicates that only the clot outline sign could act as a statistically
      significant predictor for recanalization (P = .0007). CONCLUSION: Prethrombolysis
      cerebral arteriograms demonstrating delayed antegrade contrast opacification
      distal to the occlusion site are associated with higher recanalization rates.

PMID- 16908574
TI  - Symptomatic stenosis of the cavernous portion of the internal carotid artery due
      to an irresectable medial sphenoid wing meningioma: treatment by endovascular
      stent placement.
AB  - A 48-year-old woman, with right-sided proptosis and decreased visual acuity,
      presented with acute left sensorimotor deficit. Recent ischemia in the right
      posterior watershed area was found on CT and MR imaging, as well as a right-sided
      medial sphenoid wing meningioma causing high-grade stenotic encasement of the
      cavernous portion of the right internal carotid artery. Because the patient was
      symptomatic and complete resection of the meningioma was impossible, the stenosis
      was successfully treated with a balloon-expanding stent.

PMID- 16908575
TI  - Transarterial balloon-assisted n-butyl-2-cyanoacrylate embolization of direct
      carotid cavernous fistulas.
AB  - BACKGROUND AND PURPOSE: Transarterial detachable balloon embolization of direct
      carotid cavernous fistulas (DCCFs) has become an optimal treatment. In a few
      cases, the parent artery has to be sacrificed to achieve morphologic cure. We
      present our experience with transarterial balloon-assisted n-butyl-2
      cyanoacrylate (n-BCA) embolization of DCCFs in which there was failure to achieve
      angiographic cure and preservation of parent arteries. METHODS: Of 141 patients
      with traumatic DCCFs who had been treated by transarterial embolization with
      occlusion of the fistula and parent artery preservation, 18 received
      transarterial balloon-assisted n-BCA embolization-6 for residual fistula after
      the balloons detached, 7 for recurrent fistula because of premature balloon
      deflation or migration, and 5 for repeated puncture of the detachable balloon by
      the bony fragment at the cavernous sinus. A total of 27 procedures were performed
      with an average 1.5 attempts per patient, and the volume of the n-BCA mixture
      varied from 0.5 to 2.3 mL with a mean of 0.83 mL. RESULTS: All DCCFs were
      successfully occluded by the n-BCA mixture with preservation of parent arteries.
      One patient with a giant cavernous sinus varix had a fatal subarachnoid
      hemorrhage. One had a recurrence and was treated by internal carotid artery (ICA)
      occlusion. Five had asymptomatic pseudoaneurysms at the parent artery. There was
      no adhesion of the n-BCA mixture to the protective balloon or the microcatheter
      or n-BCA reflux into the parent arteries. CONCLUSION: Transarterial balloon
      assisted n-BCA embolization is a feasible, efficient, and safe treatment for
      DCCFs when angiographic cure and ICA preservation are not achieved by
      transarterial detachable balloon embolization.

PMID- 16908576
TI  - Bovine aortic arch variant in humans: clarification of a common misnomer.
AB  - The term "bovine arch" is widely used to describe a common anatomic variant of
      the human aortic arch branching. This so-called bovine aortic arch has no
      resemblance to the bovine aortic arch. We describe the most common human aortic
      arch branching patterns and compare these with the bovine aortic arch.

PMID- 16908577
TI  - Brain abscess formation: a delayed complication of carotid blowout syndrome
      treated by self-expandable stent-graft.
AB  - A patient with hypopharyngeal cancer developed carotid blowout syndrome (CBS)
      treated by self-expandable stent-graft in the left carotid artery. CT scan for
      progressive right hemiparesis 4 months later showed multiple left cerebral
      abscesses and left carotid thrombosis. Although deployment of stent-grafts for
      CBS can achieve initial hemostasis in patients with head-and-neck cancer, the
      placement of a stent-graft in a field of necrosis and infection is associated
      with poor long-term outcome. We recommend the use of prophylactic antibiotics if
      endovascular foreign materials are placed in a contaminated field.

PMID- 16908578
TI  - Proton MR spectroscopy in neonates with perinatal cerebral hypoxic-ischemic
      injury: metabolite peak-area ratios, relaxation times, and absolute
      concentrations.
AB  - BACKGROUND: Results from cerebral proton (1)H-MR spectroscopy studies of neonates
      with perinatal hypoxic-ischemic injury have generally been presented as
      metabolite peak-area ratios, which are T1- and T2-weighted, rather than absolute
      metabolite concentrations. We hypothesized that compared with (1)H-MR
      spectroscopy peak-area ratios, calculation of absolute metabolite concentrations
      and relaxation times measured within the first 4 days after birth (1) would
      improve prognostic accuracy and (2) enhance the understanding of underlying
      neurochemical changes in neonates with neonatal encephalopathy. METHODS:
      Seventeen term infants with neonatal encephalopathy and 10 healthy controls were
      studied at 2.4T at 1 (1-3) and 2 (2-4) (median [interquartile range]) days after
      birth, respectively. Infants with neonatal encephalopathy were classified into 2
      outcome groups (normal/mild and severe/fatal), according to neurodevelopmental
      assessments at 1 year. The MR spectroscopy peak-area ratios, relaxation times,
      absolute concentrations, and concentration ratios of lactate (Lac), creatine plus
      phosphocreatine (Cr), N-acetylaspartate (NAA), and choline-containing compounds
      (Cho) from a voxel centered on the thalami were analyzed according to outcome
      group. RESULTS: Comparing the severe/fatal group with the controls (significance
      assumed with P < 0.05), we found that Lac/NAA, Lac/Cho, and Lac/Cr peak-area
      ratios increased and NAA/Cr and NAA/Cho decreased; Lac, NAA, and Cr T2s were
      increased; [Lac] was increased and [Cho], [Cr], and [NAA] decreased; and among
      the concentration ratios, only [Lac]/[NAA] was increased. Comparison of the
      normal/mild group with controls revealed no differences in peak-area ratios,
      relaxation times, or concentration ratios but decreased [NAA], [Cho], and [Cr]
      were observed in the infants with normal/mild outcome. Comparison of the
      normal/mild and severe/fatal groups showed increased Lac/NAA and Lac/Cho and
      decreased NAA/Cr and NAA/Cho peak-area ratios, reduced [NAA], and increased Lac
      T2 in the infants with the worse outcome. CONCLUSIONS: Metabolite concentrations,
      in particular [NAA], enhance the prognostic accuracy of cerebral (1)H-MR
      spectroscopy-[NAA] was the only measurable to discriminate among all (control,
      normal/mild, and severe/fatal outcome) groups. However, peak-area ratios are more
      useful prognostic indicators than concentration ratios because they depend on
      metabolite concentrations and T2s, both of which are pathologically modulated.
      Concentration ratios depend only on the concentrations of the constituent
      metabolites. Increased Cr T2 may provide an indirect marker of impaired cellular
      energetics, and similarly, NAA T2 may constitute an index of exclusively neuronal
      energy status. Our recommendation is to collect data that enable calculation of
      brain metabolite concentrations. However, if time constraints make this
      impossible, metabolite peak-area ratios provide the next best method of assigning
      early prognosis in neonatal encephalopathy.

PMID- 16908579
TI  - Serial MR imaging, diffusion tensor imaging, and MR spectroscopic findings in a
      child with progressive encephalopathy, edema, hypsarrhythmia, and optic atrophy
      (PEHO) syndrome.
AB  - PEHO syndrome is a rare symptom complex of severe progressive encephalopathy,
      edema, hypsarrhythmia, and optic atrophy. Disease onset is in early infancy. The
      current case report presents and discusses serial conventional MR imaging
      findings and serial functional studies including diffusion tensor imaging and
      quantitative MR spectroscopy findings in a 6-year-old child with PEHO.

PMID- 16908580
TI  - Epidermal nevus syndrome with internal carotid artery occlusion and intracranial
      and orbital lipomas.
AB  - We report a case of epidermal nevus syndrome involving the brain in which there
      is chronic occlusion of the left distal internal carotid artery resulting in
      ipsilateral atrophy. Orbital and cerebellopontine angle cistern lipomas and a
      wide cortical developmental malformation are associated with the condition. We
      present MR imaging findings of a patient and discuss features in the context of
      other neurocutaneous diseases.

PMID- 16908581
TI  - An unusual case of split cord malformation.
AB  - We present a variant of a split cord malformation with coexisting segmental
      spinal dysgenesis. CT myelography showed the left hemicord with a small remnant
      of subarachnoid space running through an intravertebral cleft in a spine anomaly.
      The left hemicord had no apparent intradual connection to the upper cord on any
      radiologic examination, though functional electrical stimulation studies revealed
      an intact efferent pathway that connected the left hemicord to the main spinal
      cord.

PMID- 16908582
TI  - MR angiography of the great anterior radiculomedullary artery (Adamkiewicz
      artery) validated by digital subtraction angiography.
AB  - BACKGROUND AND PURPOSE: Imaging of the anterior superficial spinal cord arteries
      by MR angiography is hindered by their small calibers and the similarity in
      configuration with the anterior superficial spinal cord veins. To validate the
      location and spatial configuration of the great anterior radiculomedullary
      artery, (ie, the Adamkiewicz artery [AKA]), contrast-enhanced MR angiography (CE
      MRA) was compared with digital subtraction angiography (DSA). METHODS: Fifteen
      patients with suspected spinal cord vascular pathology underwent both spinal CE
      MRA and selective spinal DSA. Two phase CE-MRA was performed with the use of a
      centric k-space filling scheme synchronized to the contrast bolus arrival. The
      level and side of the AKA origin were scored on the DSA and CE-MRA images and
      compared regarding image quality in terms of vessel conspicuity, contrast,
      continuity, sharpness, and background homogeneity on a relative 5-point scale.
      RESULTS: Localization and spatial configuration of the AKA by CE-MRA was in
      agreement with DSA findings in 14 of 15 cases. One mismatch of 1 vertebral level
      (not side) appeared as a result of the tangled vascular pathology. Comparison of
      image quality revealed that DSA is superior to CE-MRA concerning vessel
      continuity, sharpness, and background homogeneity (P < .001). Overall vessel
      conspicuity and contrast were judged to be similar. CONCLUSION: CE-MRA can
      visualize and localize the level of the AKA correctly. Image quality of CE-MRA is
      sufficient for detection of the AKA but is inferior to DSA.

PMID- 16908583
TI  - MR angiography of the Adamkiewicz artery and anterior radiculomedullary vein:
      postmortem validation.
AB  - SUMMARY: Spinal cord arteries and veins are difficult to visualize and
      distinguish by MR angiographic techniques because of their small sizes, similar
      spatial course, and close vascular anatomy. Contrast-enhanced MR angiography was
      demonstrated to dynamically resolve the Adamkiewicz artery from the anterior
      radiculomedullary vein in the thoracolumbar spinal cord. The location of the
      Adamkiewicz artery and the anterior radiculomedullary vein could be validated in
      the postmortem specimen of a thoracoabdominal aortic aneurysm patient.

PMID- 16908584
TI  - Pseudoaneurysm of the anterior spinal artery in a patient with Moyamoya: an
      unusual cause of subarachnoid hemorrhage.
AB  - Subarachnoid hemorrhage (SAH) is a recognized presentation of Moyamoya disease in
      adults. Because there are extensive collateral networks and potential
      complications that develop, a thorough investigation of the intracranial and
      extracranial circulation is necessary to exclude a treatable cause when these
      patients present with SAH. We present a case of SAH due to a ruptured
      pseudoaneurysm of the anterior spinal artery arising from the supreme intercostal
      artery, which was the sole source of blood supply to the intracranial
      circulation.

PMID- 16908585
TI  - Pain response in the first trimester after percutaneous vertebroplasty in
      patients with osteoporotic vertebral compression fractures with or without bone
      marrow edema.
AB  - BACKGROUND AND PURPOSE: Presence of bone marrow edema (BME) in osteoporotic
      vertebral compression fractures (VCF) detected by MR imaging as selection
      criterion for percutaneous vertebroplasty (PV) is speculative. To clarify
      significance of BME in VCF, we assessed pain response after PV in patients with
      VCF with full BME versus patients with VCF with absent BME. METHODS: From a
      cohort of patients with painful VCF selected for PV, pain response in 14 patients
      with absent BME in VCF was prospectively compared with pain response in 31
      patients with full BME in VCF. Pain was evaluated before PV and at 1 and 3 months
      after PV with visual analog scores and analgesics used. Back pain in general and
      at treated vertebral levels was assessed. RESULTS: Pain decrease after PV at
      treated levels was observed in 10 (71%) patients with absent BME in VCF at both
      follow-up periods and in 29 (94%) patients with full BME 1 month after PV and 30
      (97%) at 3 months after PV. Differences between the groups were significant (P =
      .04 at 1 month; P = .01 at 3 months). Pain response was not affected by other
      patient or imaging characteristics. General back pain after PV was comparable in
      both groups after PV (P = .08 at 1 month; P = .4 at 3 months). CONCLUSION: Pain
      decrease after PV in patients with VCF is more frequently observed when full BME
      is present. Because 71% of patients with VCF with absent BME responded favorably
      on pain, PV should not be withheld based on absence of BME alone.

PMID- 16908586
TI  - Subsequent vertebral fractures after vertebroplasty: association with
      intraosseous clefts.
AB  - BACKGROUND AND PURPOSE: Patients with vertebral fractures containing intraosseous
      clefts may represent a distinct subgroup of vertebroplasty patients, yet the
      development of subsequent vertebral fractures in this population has not been
      explored. We tested the hypothesis that after vertebroplasty for intraosseous
      clefts, subsequent fractures would occur earlier and more frequently than after
      treatment of non-cleft-containing fractures. METHODS: We retrospectively reviewed
      362 patients treated with vertebroplasty for osteoporotic fractures. The
      location, frequency, and timing of subsequent fractures were compared between 2
      subgroups: group 1, patients treated at fractures containing clefts, and group 2,
      treated patients without clefts. A vertebra-by-vertebra analysis was used to
      compare the relative risk and timing of subsequent fractures adjacent to
      vertebrae with or without clefts. RESULTS: Group 1 included 63 patients treated
      at 65 vertebrae and group 2 included 250 patients treated at 399 vertebrae. Group
      1 demonstrated a nearly twofold increased risk of subsequent fracture (odds ratio
      [OR], 1.90; 95% confidence interval [CI], 1.04-3.49, P = .037). At the vertebral
      level, the relative risk of subsequent fracture was 2.02 (95% CI, 1.46-2.58; P =
      .013) times greater adjacent to a treated cleft. Fractures adjacent to any
      treated level occurred significantly sooner than nonadjacent fracture (P =
      .0004). The presence of a cleft was not significantly associated with the timing
      of subsequent fractures. CONCLUSIONS: Patients with osteoporotic vertebral
      fractures containing clefts are at increased risk for subsequent fractures and
      treatment of these clefts is associated with increased rates of adjacent
      fracture. There is no significant difference in the timing of subsequent
      fractures based on the presence of a cleft.

PMID- 16908587
TI  - Posterior epidural migration of a sequestrated lumbar disk fragment: MR imaging
      findings.
AB  - We present a 75-year-old man who, for 2 weeks, had progressive pain in both of
      his thighs when standing straight. MR imaging showed a sequestrated disk
      fragment, which had a signal intensity similar to that of a herniated disk with a
      rim enhancement in the posterior epidural space and a ruptured outermost annulus
      of the intervertebral disk at L2-3. Awareness of these MR imaging findings can
      help in the diagnosis of posterior epidural disk migration.

PMID- 16908592
TI  - Tumor necrosis factor-alpha differentially modulates CD44 expression in ovarian
      cancer cells.
AB  - Chronic inflammation is implicated in the pathophysiology of ovarian cancer.
      Tumor necrosis factor-alpha (TNF-alpha), a major inflammatory cytokine, is
      abundant in the ovarian cancer microenvironment. TNF-alpha modulates the
      expression of CD44 in normal T lymphocytes and CD44 is implicated in ovarian
      carcinogenesis and metastases. However, little is known about the role of TNF
      alpha in CD44 expression of cancer cells. Recent clinical work using TNF-alpha
      inhibitors for the treatment of ovarian cancer makes the study of TNF-alpha
      interactions with CD44 crucial to determining treatment a success or a failure.
      We studied the effect of TNF-alpha on ovarian cancer cells viability, CD44
      expression, and in vitro migration/invasion. Our results revealed that TNF-alpha
      differentially modulates the expression of CD44 in TNF-alpha-resistant ovarian
      cancer cells, affecting their in vitro migration, invasion, and binding to
      hyaluronic acid. TNF-alpha up-regulation of CD44 expression was dependent on the
      activation of c-Jun NH(2)-terminal kinase (JNK) and this activation was
      accompanied by an increase in their invasive phenotype. On the contrary, if TNF
      alpha failed to induce JNK phosphorylation, the end result was down-regulation of
      both CD44 expression and the invasive phenotype. These results were confirmed by
      the use of JNK inhibitors and a TNF receptor competitive inhibitor.

PMID- 16908593
TI  - Cyclooxygenase-2 is involved in S100A2-mediated tumor suppression in squamous
      cell carcinoma.
AB  - S100A2 is considered a putative tumor suppressor due to its loss or down
      regulation in several cancer types. However, no mechanism has been described for
      the tumor suppressor role of S100A2. In this study, ectopic expression of S100A2
      in the human malignant squamous cell carcinoma cell line KB resulted in a
      significant inhibition of proliferation, migration, and invasion. Moreover,
      S100A2 significantly reduced the number of colonies (>or=0.5 mm) formed in
      semisolid agar and decreased tumor growth and burden in nude mice. cDNA
      microarray analysis was used to compare mRNA expression profiles of vector- and
      S100A2-expressing isogenic cells. Among the genes deregulated by S100A2, the
      expression of cyclooxygenase-2 (COX-2) mRNA was significantly suppressed by
      S100A2 (2.4-fold). Western blot analysis confirmed that S100A2 reduced the
      expression of COX-2 protein in stably and transiently transfected KB and RPMI
      2650 cells. COX-2 is frequently overexpressed in various types of cancer and
      plays an important role in tumor progression. Partial restoration of COX-2
      expression attenuated the antitumor effect of S100A2 both in vitro and in vivo.
      Although the interplay between S100A2 and COX-2 remains to be clarified, these
      findings first showed a potent antitumor role of S100A2 in squamous cell
      carcinoma partly via reduced expression of COX-2.

PMID- 16908594
TI  - Delta9-tetrahydrocannabinol-induced apoptosis in Jurkat leukemia T cells is
      regulated by translocation of Bad to mitochondria.
AB  - Plant-derived cannabinoids, including Delta9-tetrahydrocannabinol (THC), induce
      apoptosis in leukemic cells, although the precise mechanism remains unclear. In
      the current study, we investigated the effect of THC on the upstream and
      downstream events that modulate the extracellular signal-regulated kinase (ERK)
      module of mitogen-activated protein kinase pathways primarily in human Jurkat
      leukemia T cells. The data showed that THC down-regulated Raf-1/mitogen-activated
      protein kinase/ERK kinase (MEK)/ERK/RSK pathway leading to translocation of Bad
      to mitochondria. THC also decreased the phosphorylation of Akt. However, no
      significant association of Bad translocation with phosphatidylinositol 3
      kinase/Akt and protein kinase A signaling pathways was noted when treated cells
      were examined in relation to phosphorylation status of Bad by Western blot and
      localization of Bad to mitochondria by confocal analysis. Furthermore, THC
      treatment decreased the Bad phosphorylation at Ser(112) but failed to alter the
      level of phospho-Bad on site Ser(136) that has been reported to be associated
      with phosphatidylinositol 3-kinase/Akt signal pathway. Jurkat cells expressing a
      constitutively active MEK construct were found to be resistant to THC-mediated
      apoptosis and failed to exhibit decreased phospho-Bad on Ser(112) as well as Bad
      translocation to mitochondria. Finally, use of Bad small interfering RNA reduced
      the expression of Bad in Jurkat cells leading to increased resistance to THC
      mediated apoptosis. Together, these data suggested that Raf-1/MEK/ERK/RSK
      mediated Bad translocation played a critical role in THC-induced apoptosis in
      Jurkat cells.

PMID- 16908595
TI  - Mitotic arrest, apoptosis, and sensitization to chemotherapy of melanomas by
      methionine deprivation stress.
AB  - Methionine deprivation stress (MDS) eliminates mitotic activity in melanoma cells
      regardless of stage, grade, or TP53 status, whereas it has a negligible effect on
      normal skin fibroblasts. In most cases, apoptosis accounts for the elimination of
      up to 90% of tumor cells from the culture within 72 hours after MDS, leaving a
      scattered population of multinucleated resistant cells. Loss of mitosis in tumor
      cells is associated with marked reduction of cyclin-dependent kinase (CDK) 1
      transcription and/or loss of its active form (CDK1-P-Thr(161)), which is
      coincident with up-regulation of CDKN1A, CDKN1B, and CDKN1C (p21, p27, and p57).
      Expression of the proapoptotic LITAF, IFNGR, EREG, TNFSF/TNFRSF10 and TNFRSF12,
      FAS, and RNASEL is primarily up-regulated/induced in cells destined to undergo
      apoptosis. Loss of Aurora kinase B and BIRC5, which are required for histone H3
      phosphorylation, is associated with the accumulation of surviving multinucleated
      cells. Nevertheless, noncycling survivors of MDS are sensitized to temozolomide,
      carmustin, and cisplatin to a much greater extent than normal skin fibroblasts
      possibly because of the suppression of MGMT/TOP1/POLB, MGMT/RAD52/RAD54, and
      cMET/RADD52, respectively. Sensitivity to these and additional genotoxic agents
      and radiation may also be acquired due to loss of cMET/OGG1, reduced glutathione
      reductase levels, and a G(2)-phase block that is a crucial step in the damage
      response associated with enhancement of drug toxicity. Although the genes
      controlling mitotic arrest and/or apoptosis in response to low extracellular
      methionine levels are unknown, it is likely that such control is exerted via the
      induction/up-regulation of tumor suppressors/growth inhibitor genes, such as
      TGFB, PTEN, GAS1, EGR3, BTG3, MDA7, and the proteoglycans (LUM, BGN, and DCN), as
      well as the down-regulation/loss of function of prosurvival genes, such as
      NFkappaB, MYC, and ERBB2. Although MDS targets several common genes in tumors,
      mutational variability among melanomas may decide which metabolic and signal
      transduction pathways will be activated or shutdown.

PMID- 16908597
TI  - Modification of OATP2B1-mediated transport by steroid hormones.
AB  - The family of the organic anion transporting polypeptides forms an increasing
      group of uptake transport proteins with a wide substrate spectrum. Although the
      expression of some members of this group, such as organic anion transporting
      polypeptide (OATP)-A or C, is limited to special tissues (such as liver or
      brain), the organic anion transporting polypeptide 2B1 (OATPB/SLCO2B1) is
      expressed in many organs, including liver, placenta, mammary gland, brain, and
      intestine. However, little is known about its function in those tissues because
      only a limited number of compounds, such as dehydroepiandrosterone-sulfate
      (DHEAS) and estrone-3-sulfate (E3S), have been characterized as OATP2B1
      substrates. To further elucidate the role of OATP2B1 on steroid transport, we
      examined the influence of steroid hormones on OATP2B1-mediated E3S and DHEAS
      uptake using OATP2B1-overexpressing Madin-Darby canine kidney II cells. We
      identified unconjugated androgens (e.g., testosterone) as potent inhibitors for
      OATP2B1. In contrast, gestagenes such as progesterone enhanced E3S uptake in a
      concentration-dependent manner to up to 300% of the control, accompanied by a
      significant decrease in the OATP2B1 K(m) value for E3S (control, K(m) = 14
      microM; in the presence of 31.6 muM progesterone, K(m) = 3.6 microM). Moreover,
      we demonstrated that testosterone and progesterone are not substrates of OATP2B1,
      indicating an allosteric mechanism for the observed effects. Furthermore, we
      showed that progesterone enhances the OATP2B1-dependent pregnenolone sulfate
      transport. Taken together, the results indicate functional modification of
      OATP2B1-mediated E3S and DHEAS as well as pregnenolone sulfate transport through
      steroid hormones such as progesterone. These effects can have physiological
      consequences for the organ-specific uptake of steroids.

PMID- 16908598
TI  - Corticostriatal up-regulation of activity-regulated cytoskeletal-associated
      protein expression after repeated exposure to cocaine.
AB  - We provide evidence that cocaine evokes short- and long-lasting increases in
      activity-regulated cytoskeletal-associated protein (Arc) expression after a
      finely tuned, time-dependent and regional-selective expression profile. Acute
      experiments revealed that cocaine up-regulates Arc expression primarily in
      striatum and prefrontal cortex through a dopamine D1-dependent mechanism and a
      combination of D1- and D2-dependent mechanisms, respectively. Aside from cocaine
      dependent Arc elevation, we show for the first time that D1 and D2 receptors
      tonically regulate basal Arc expression following a regional-selective profile.
      As opposed to the effects of a single cocaine injection on Arc expression, which
      dissipate within 24 h, subchronic (five daily injections) or chronic (14 daily
      injections) cocaine administration, with animals sacrificed hours or days after
      the last treatment, demonstrated that Arc expression is still up-regulated long
      after treatment cessation, suggesting that adaptive changes have been set in
      motion by the prolonged administration of the psychostimulant. In summary, our
      findings are the first to demonstrate that repeated exposure to cocaine leads to
      long-lasting dysregulation of Arc expression in the corticostriatal network, thus
      establishing a molecular basis to explain, at least partially, the impaired
      synaptic transmission caused by cocaine abuse at this level. Furthermore, given
      the role exerted by Arc in cytoarchitectural rearrangements, it is conceivable to
      speculate that it mediates changes in synaptic connectivity brought about by
      cocaine. Our findings thus pinpoint this molecule as a neuropathological
      underpinning and molecular bridge that connects short- and long-term neuronal
      modifications associated with cocaine abuse.

PMID- 16908599
TI  - Induction of apoptosis in estrogen receptor-negative breast cancer cells by
      natural and synthetic cyclopentenones: role of the IkappaB kinase/nuclear factor
      kappaB pathway.
AB  - Nuclear factor-kappaB (NF-kappaB), a transcription factor with a critical role in
      promoting inflammation and cell survival, is constitutively activated in estrogen
      receptor (ER)-negative breast cancer and is considered a potential therapeutic
      target for this type of neoplasia. We have previously demonstrated that
      cyclopentenone prostaglandins are potent inhibitors of NF-kappaB activation by
      inflammatory cytokines, mitogens, and viral infection, via direct binding and
      modification of the beta subunit of the IkappaB kinase complex (IKK). Herein, we
      describe the NF-kappaB-dependent anticancer activity of natural and synthetic
      cyclopentenone IKK inhibitors. We demonstrate that the natural cyclopentenone 15
      deoxy-Delta(12,14)prostaglandin J(2) (15d-PGJ(2)) is a potent inhibitor of
      constitutive IkappaB-kinase and NF-kappaB activities in chemotherapy-resistant ER
      negative breast cancer cells. 15d-PGJ(2)-induced inhibition of NF-kappaB function
      is rapidly followed by down-regulation of NF-kappaB-dependent antiapoptotic
      proteins cIAPs 1/2, Bcl-X(L), and cellular FLICE-inhibitory protein, leading to
      caspase activation and induction of apoptosis in breast cancer cells resistant to
      treatment with paclitaxel and doxorubicin. We then demonstrate that the
      cyclopentenone ring structure is responsible for these activities, and we
      identify a new synthetic cyclopentenone derivative, 3-tert-butyldimethylsilyloxy
      5-(E)-iso-propylmethylenecyclopent-2-enone (CTC-35), as a potent NF-kappaB
      inhibitor with proapoptotic activity in ER-negative breast cancer cells. The
      results open new perspectives in the search for novel proapoptotic molecules
      effective in the treatment of cancers presenting aberrant NF-kappaB regulation.

PMID- 16908600
TI  - Involvement of tissue plasminogen activator-plasmin system in depolarization
      evoked dopamine release in the nucleus accumbens of mice.
AB  - Tissue plasminogen activator (tPA), a serine protease, catalyzes the conversion
      of plasminogen to plasmin. In the present study, we investigated the role of the
      tPA-plasmin system in depolarization-evoked dopamine (DA) and acetylcholine (ACh)
      release in the nucleus accumbens (NAc) and hippocampus, respectively, of mice, by
      using in vivo microdialysis. Microinjection of either tPA or plasmin
      significantly potentiated 40 mM KCl-induced DA release without affecting basal DA
      levels. In contrast, plasminogen activator inhibitor-1 dose-dependently reduced
      60 mM KCl-induced DA release. The 60 mM KCl-evoked DA release in the NAc was
      markedly diminished in tPA-deficient (tPA-/-) mice compared with wild-type mice,
      although basal DA levels did not differ between the two groups. Microinjections
      of either exogenous tPA (100 ng) or plasmin (100 ng) into the NAc of tPA-/-mice
      restored 60 mM KCl-induced DA release, as observed in wild-type mice. In
      contrast, there was no difference in either basal or 60 mM KCl-induced ACh
      release in the hippocampus between wild-type and tPA-/-mice. Our findings suggest
      that the tPA-plasmin system is involved in the regulation of depolarization
      evoked DA release in the NAc.

PMID- 16908601
TI  - Philanthropy, ethics, and leadership in academic psychiatry.

PMID- 16908602
TI  - Psychiatrists as leaders in academic medicine.

PMID- 16908603
TI  - Assessing the ACGME Competencies in Psychiatry Training programs.

PMID- 16908604
TI  - Leadership for psychiatrists.
AB  - OBJECTIVE: This article introduces the prospective leader to a set of questions
      and relevant leadership literature that aid in the process of deciding whether to
      accept a leadership position. METHOD: The author conducted a review of literature
      and discussion with leaders in psychiatry and other medical disciplines. RESULTS:
      The questions posed and leadership literature discussed provide a useful set of
      guidelines for potential leaders in deciding whether to accept or continue in a
      leadership position. CONCLUSIONS: Having access to mentoring, a clear description
      of "expected results," personal appreciation of leadership style, a description
      of available resources, a leadership vision in line with the institutional
      vision, and an appreciation of the necessary time commitments are fundamental in
      deciding whether to accept a leadership position.

PMID- 16908605
TI  - Leadership: from a psychiatric to an institutional perspective.

PMID- 16908606
TI  - The tripartite mission of an academic psychiatry department and the roles of the
      chair.
AB  - Within academic medical centers, psychiatry, pediatrics, and certain other
      specialties of internal medicine carry a disproportionate responsibility for
      teaching but are least able to support teaching and research through clinical
      income. This article reviews the educational, research and clinical missions of
      an academic psychiatry department and the major challenges facing chairs as they
      seek to lead their departments. Though the leadership role that the chair plays
      in psychiatric education, research, and clinical services can be tremendously
      satisfying, it is also true that being a chair in these times has much in common
      with "middle management" in other corporate structures.

PMID- 16908607
TI  - Advice for chairs of academic departments of psychiatry: the "Ten Commandments".

PMID- 16908608
TI  - A tool kit for new chairs.
AB  - Many chairs come to their position without the benefit of previous experience in
      the role of leading an academic department. The American Association of Chairs of
      Departments of Psychiatry (AACDP) identified the need for a manual designed to
      help a new chair get started. The "tool kit" that emerged contains sections that
      describe the AACDP, outline key issues and responsibilities of a department
      chair, and review a variety of resources available to assist a new chair. The
      manual is used to supplement orientation sessions at AACDP meetings and is given
      to new chairs who are unable to attend these sessions.

PMID- 16908609
TI  - The Seven Deadly Sins of academic chairs.

PMID- 16908610
TI  - Reflections on leadership as chair of a department of psychiatry.
AB  - The chair of a department of psychiatry has a complex role, balancing leadership
      of the department with the broader role as an institutional leader. The
      competencies and training opportunities for this role are ill-defined.
      Mentorship, strong administrative supports, and champions for psychiatry within
      the academic health center are key resources for the chair. The continued need to
      be a knowledgeable leader in the national trends of education, research, and
      clinical systems of care is a real challenge.

PMID- 16908611
TI  - Women chairs in psychiatry: a collective reflection.
AB  - OBJECTIVE: This article describes the experiences of women chairs in psychiatry.
      METHOD: All women chairs in psychiatry were contacted by the author to share
      their personal experiences as chair. Seven out of 10 chairs accepted the
      invitation. A similar invitation was extended to a few female and male academics.
      CONCLUSIONS: Women in chair positions come from smaller schools and departments,
      have clinical and educational backgrounds, have fewer grants than their male
      counterparts, and are more likely to be recruited from within. Most of the women
      did not aspire to be chair, but after an initial adjustment period, they felt
      their job to be less stressful. Mentors played a role in the careers of some, but
      not all women chairs.

PMID- 16908612
TI  - Utilization of a formative evaluation card in a psychiatry clerkship.
AB  - OBJECTIVE: This article discusses how formative feedback to medical students
      during their clinical rotations facilitates their successfully meeting the
      rotation's educational objectives. To help students initiate mid-rotation
      feedback and to help preceptors structure that feedback, the authors designed the
      Instant Feedback Card (IFc). The goal of this study was to examine the degree to
      which the IFc facilitated the formative feedback process from the perspectives of
      both students and faculty. METHOD: The IFc contains a checklist of the 13
      clinical competencies that are also used to provide summative evaluations to
      students. One hundred and sixty-five medical students completing a 6-week
      psychiatry clerkship between January and December 2004 were given an IFc to
      present to their inpatient preceptor at one of their two inpatient sites. At the
      end of each 3-week inpatient rotation, all students were e-mailed a brief
      questionnaire about the formative feedback received during the preceding
      rotation. At the end of the 12-month study period, faculty were e-mailed a brief
      questionnaire about how useful the IFc was in helping to facilitate the feedback
      process. RESULTS: One hundred thirty-eight students (80%) participated in the
      study and returned 267 questionnaires (1.9/student, 97% response rate). Two
      hundred five students indicated on 77% of the questionnaires returned that they
      received mid-rotation feedback and of those, 84% revealed that feedback was
      helpful. Eighty-five percent of the students received mid-rotation feedback when
      they used the IFc and only 69% received mid-rotation feedback without the IFc. A
      majority of the 14 faculty serving as inpatient preceptors during the study
      period found the cards useful for stimulating feedback discussions, for reducing
      the stress of providing feedback, and for getting students to request feedback.
      CONCLUSIONS: The results of this pilot study are not definitive, but they do
      indicate that the Instant Feedback card (IFc) did facilitate the process and
      structure of providing and receiving formative feedback as indicated by a
      significantly greater number of students receiving formative feedback when they
      used the IFc.

PMID- 16908613
TI  - Choosing a career in psychiatry: influential factors within a medical school
      program.
AB  - OBJECTIVE: To examine the influence of initial interest, pre-clerkship
      experiences, clerkship experiences, and enrichment activities on choosing a
      career in psychiatry. METHOD: Residents in psychiatry at the authors' medical
      school completed a survey that examined each of these factors in relation to
      career choice. RESULTS: Thirty participants ranked initial interest as the most
      influential factor. Thirteen residents with low initial interest ranked clerkship
      experiences and negative experiences in other specialties as more influential
      than the 17 residents with high initial interest. Twelve residents who had
      attended the authors' medical school rated enrichment activities, particularly
      psychiatry electives, as more influential than the remaining 18 from other
      medical schools did. CONCLUSIONS: Although limited by small sample size and
      potential recall biases, this study suggests that positive clerkship experiences
      and participation in psychiatry electives may be modifiable programmatic factors
      that could enhance recruitment to psychiatry.

PMID- 16908614
TI  - Assessing the ACGME Competencies in Psychiatry Training programs.
AB  - In 2000, the Accreditation Council of Graduate Medical Education (ACGME) laid out
      a definition of competence that included six specific areas of focus: patient
      care (including clinical reasoning), medical knowledge, practice-based learning
      and improvement, interpersonal and communication skills, professionalism, and
      systems-based practice. The ACGME's intention was to mandate increasingly
      reliable and valid assessment measures to be used by all training programs over
      the next decade, with the goal of providing "more credible, accurate, reliable
      and useful educational outcome data." In this article, the authors will review
      definitions of competency according to the new ACGME standards and examine the
      assessment tools currently available, including global evaluations, 360-degree
      evaluations, checklists, standardized examinations and direct observations. The
      authors will provide an overview of critical considerations in different
      assessment methods, including timing, psychometric properties, benchmarks, and
      feedback. Finally, the authors will discuss the relevant literature concerning
      the strengths and weaknesses of these various assessment tools. Throughout, the
      authors will comment on the applicability of the literature on assessment to the
      field of psychiatry and consider directions for competency assessment within and
      beyond psychiatric training. Following the paper is an annotated bibliography of
      the literature for those wishing to explore this topic more deeply and a list of
      web-based resources that may be used by those wishing to access available
      instruments.

PMID- 16908615
TI  - Comparison of burnout among medical residents before and after the implementation
      of work hours limits.
AB  - OBJECTIVE: The authors assess whether implementation of work hour limits is
      associated with a lower prevalence of medical resident burnout. METHOD: A survey
      was mailed to medical residents in different medical specialties at one
      university. RESULTS: Somewhat lower burnout prevalence was reported among
      residents after implementation of work hour limits compared with the rates prior
      to the implementation period. The decrease in burnout prevalence occurred
      primarily among PGY-1 residents. Prevalence of burnout increased with hours
      worked. CONCLUSIONS: Implementing work hour limits appeared to reduce burnout
      prevalence.

PMID- 16908616
TI  - Inter-site consistency at a multi-site psychiatry clerkship.
AB  - OBJECTIVE: This study examines the effects of clinical site assignment within a
      multiple-site psychiatry clerkship program on the convergent outcome of the
      National Board of Medical Examiners (NBME) subject examination. METHOD: NBME
      scores, controlled for baseline pre-clerkship knowledge base as measured by
      second year human behavior scores, were compared for inpatient and outpatient
      clinical clerkship sites. RESULTS: No effect of clinical site assignment on NBME
      scores was demonstrated, suggesting that inter-site consistency occurred for the
      performance outcomes measured. CONCLUSIONS: Similar assessments can help other
      clerkship directors monitor clinical sites for quality of their educational
      programs, which is increasingly important as medical schools expand their
      clinical sites to community-based programs.

PMID- 16908617
TI  - Early manifestation of type 1 diabetes in children is a risk factor for changed
      bone geometry: data using peripheral quantitative computed tomography.
AB  - OBJECTIVE: Normal to severely decreased bone mineral density has been reported in
      children with type 1 diabetes. To detect possible abnormalities in bone
      mineralization, geometry, and muscle bone unit, we measured selective parameters
      in children with type 1 diabetes using peripheral quantitative computed
      tomography. METHODS: Measurements of the radius by peripheral quantitative
      computed tomography were made to assess cortical and trabecular bone
      characteristics as well as muscle mass in 88 patients (42 girls, 46 boys) at a
      mean age of 11.7 +/- 3.0 years, a mean disease duration of 5.6 +/- 3.7 years, and
      a mean manifestation age of type 1 diabetes of 6.1 +/- 3.5 years. Height, weight,
      Tanner stage, insulin regimen, and glycosylated hemoglobin values were recorded.
      Bone metabolism was studied by measurement of bone formation and bone resorption
      parameters. Dynamic muscle force was measured using a grip strength device.
      RESULTS: Overall, cortical, trabecular, and total bone mineral density were
      within the reference range. Total and cortical bone cross-sectional area and
      muscle mass were low in prepubertal patients, and total cross-sectional area was
      low in early puberty. Adolescent patients showed normal bone and muscle
      parameters. Grip strength and recreational physical activity were normal in all
      in relation to a healthy reference population. In a subgroup of 18 patients,
      early manifestation of type 1 diabetes was detected as a risk factor for altered
      bone development with significantly reduced cortical bone mineral density and
      total, cortical, and muscle cross-sectional area (-0.9 +/- 1.3 SD, -2.1 +/- 1.3
      SD, -1.6 +/- 0.7 SD, and -1.0 +/- 0.7 SD, respectively). Bone characteristics
      were not influenced by metabolic control, disease duration, or insulin regimen.
      CONCLUSIONS: Manifestation of type 1 diabetes at an early age may impair bone
      development. Longitudinal data are needed to determine whether this impairment
      persists into adolescence and adulthood.

PMID- 16908618
TI  - Therapy of parapneumonic effusions in children: video-assisted thoracoscopic
      surgery versus conventional thoracostomy drainage.
AB  - OBJECTIVE: Controversy surrounds the optimal treatment of parapneumonic
      effusions. This trial of pediatric patients with community-acquired pneumonia and
      associated parapneumonic processes compared primary video-assisted thoracoscopic
      surgery with conventional thoracostomy drainage. DESIGN: A prospective,
      randomized trial was conducted at DeVos Children's Hospital (Grand Rapids, MI)
      between November 2003 and May 2005. All of the patients under 18 years of age
      with large parapneumonic effusions were approached for enrollment in the study.
      After enrollment, each patient was randomly assigned to receive either video
      assisted thoracoscopic surgery or thoracostomy tube drainage of the effusion.
      Subsequent therapies (fibrinolysis, imaging, and further drainage procedures)
      were similar for each group per protocol. RESULTS: Eighteen patients were
      enrolled in the study: 10 in video-assisted thoracoscopic surgery and 8 in
      conventional thoracostomy. The groups were demographically similar. No
      mortalities were encountered in either group, and everyone was discharged from
      the hospital with acceptable outcomes. Yet, there were multiple variables that
      demonstrated statistical difference. Hospital length of stay, number of chest
      tube days, narcotic use, number of radiographic procedures, and interventional
      procedures were all less in the patients who underwent primary video-assisted
      thoracoscopic surgery. In addition, no patient in the video-assisted
      thoracoscopic surgery group required fibrinolytic therapy, which was also
      statistically different from the thoracostomy drainage group. CONCLUSIONS: The
      outcomes of this study strongly suggest that primary video-assisted thoracoscopic
      surgery for evacuation of parapneumonic effusions is superior to conventional
      thoracostomy drainage.

PMID- 16908619
TI  - Olfactory disorder in children with 22q11 deletion syndrome.
AB  - OBJECTIVE: 22q11 deletion syndrome, a common human interstitial deletion syndrome
      (1:5000), is associated with a heterogeneous physical phenotype, including
      several factors that markedly increase the risk for olfactory disorder. Despite
      its potential consequences, pediatric studies of impaired olfaction are rare, and
      odor detection in children with 22q11 deletion syndrome has not yet been
      examined. METHODS: The University of Pennsylvania Smell Identification Test was
      administered to 62 children, including 39 with 22q11 deletion syndrome and 23
      neurotypical control siblings who ranged in age from 5.3 to 14.8 years. Lowered
      smell detection accuracy among affected children was predicted. RESULTS:
      Substantially more children with 22q11 deletion syndrome (68%) as compared with
      neurotypical control subjects (13%) had University of Pennsylvania Smell
      Identification Test scores > or = 2 SDs below the standardization sample mean.
      Frequency of impairment in younger versus older children did not differ. The
      score distributions of children with and without velopharyngeal insufficiency did
      not differ; however, markedly lower score variance among children with
      velopharyngeal insufficiency suggested its negative impact on olfaction. Posthoc
      error analyses revealed that affected children had special difficulty detecting
      smells that are associated with fumes and smoke. CONCLUSIONS: Odor detection
      failures are ubiquitous among children with 22q11 deletion syndrome and are not
      associated with developmental delay or performance characteristics of younger
      affected children. Additional studies are needed to examine further the impact on
      olfaction of velopharyngeal insufficiency and compromised nasal airway patency.
      Children with 22q11 deletion syndrome should be evaluated routinely for olfactory
      disorder. When deficits are identified, caregivers should be warned of potential
      dangers that are associated with this type of sensory impairment.

PMID- 16908620
TI  - Erythropoietin concentrations and neurodevelopmental outcome in preterm infants.
AB  - OBJECTIVE: Erythropoietin therapy is effective in decreasing transfusions to
      varying degrees in preterm infants. Recent animal studies using erythropoietin
      doses to achieve serum concentrations > 1000 mU/mL report neuroprotective
      effects. We evaluated the relationship between erythropoietin concentrations and
      neurodevelopmental outcome in extremely low birth weight infants. METHODS:
      Preterm infants who weighed < or = 1000 g at birth were randomly assigned to
      erythropoietin (400 U/kg 3 times per week) or placebo/control. Therapy was
      initiated by 4 days after birth and continued through the 35th postmenstrual
      week. All infants received supplemental parenteral and enteral iron. Peak serum
      erythropoietin concentrations were obtained every 2 weeks. Follow-up evaluation
      included anthropometric measurements, Bayley scales of mental and psychomotor
      development, neurologic examination, and determination of overall
      neurodevelopmental impairment. Data were collected at 18 to 22 months' corrected
      age by certified examiners who were masked to the treatment group. Analyses were
      performed to identify correlations between erythropoietin concentrations and
      outcomes. RESULTS: Sixteen extremely low birth weight infants were enrolled; 1
      infant died at 2 weeks (placebo/control), and 15 had erythropoietin
      concentrations measured (7 erythropoietin, 8 placebo/control). Peak
      erythropoietin concentrations were significantly different between groups during
      the study (erythropoietin: 2027 +/- 1464 mU/mL; placebo/control: 26 +/- 11
      mU/mL). Before follow-up, 3 infants died (1 erythropoietin, 2 placebo/control),
      and 12 were available for follow-up (6 erythropoietin, 6 placebo/control). At 18
      to 22 months' follow-up, none of the erythropoietin recipients and 2 of the
      placebo/control infants had Mental Development Index scores < 70. Erythropoietin
      recipients had Mental Development Index scores of 96 +/- 11, and placebo/control
      infants had Mental Development Index scores of 78 +/- 7. Psychomotor Development
      Index scores were similar between groups (87 +/- 13 vs 80 +/- 7). There were no
      differences between groups with respect to anthropometric measurements. Two of 6
      infants in the erythropoietin group and 4 of 6 infants in the placebo/control
      group had some form of neurodevelopmental impairment. Posthoc analysis showed
      that infants with erythropoietin concentrations > or = 500 mU/mL had higher
      Mental Development Index scores than infants with erythropoietin concentrations <
      500 mU/mL. CONCLUSIONS: Erythropoietin concentrations did not correlate with
      Psychomotor Development Index or overall incidence of neurodevelopmental
      impairment; however, infants with elevated erythropoietin concentrations had
      higher Mental Development Index scores than those with lower erythropoietin
      concentrations. Close follow-up of infants who are enrolled in large,
      multicenter, high-dose erythropoietin studies is required to determine whether a
      correlation exists between elevated erythropoietin concentrations and improved
      neurodevelopmental outcome.

PMID- 16908621
TI  - Combined treatment of steroids and cyclosporine in Kimura disease.
AB  - Kimura disease is a rare but distinctive chronic eosinophilic inflammatory
      disorder that is characterized by tumor-like lesions in the soft tissue and lymph
      nodes of the head and neck or parotid gland. Recently, many immunopathogenetic
      features of underlying T lymphocytes and related cytokines have been noted in
      Kimura disease. However, few previous studies have investigated the serial levels
      of cytokines in children. In this report we describe an 11-year-old Japanese boy
      with relapsing Kimura disease. Before the diagnosis of Kimura disease, the
      patient had a swelling on his left neck. Steroids were effective, but the tumor
      relapsed within a few months as the steroids were tapered. He was treated with
      steroids and cyclosporine. This treatment was done by measuring serial levels of
      serum soluble interleukin-2 receptor, interleukin-4, interleukin-5, and
      eosinophil cationic protein. These results suggest the activation of T-helper
      cells and T-helper 2 cytokines, that after activated B cells and eosinophilic
      infiltration play an important role in Kimura disease, and that cyclosporine
      suppresses the activity of this disease.

PMID- 16908622
TI  - Probable intrafamilial transmission of coxsackievirus b3 with vertical
      transmission, severe early-onset neonatal hepatitis, and prolonged viral RNA
      shedding.
AB  - Here we report a familial cluster of 3 cases of coxsackievirus B3 infection: a
      recent history of illness in a woman's 3-year-old son with a coxsackievirus B3
      positive stool culture indicated that he probably infected his mother at home
      during her last week of pregnancy. Consequently, she delivered an infected
      neonate who developed severe hepatitis, disseminated intravascular coagulation,
      and bilateral intracranial hemorrhage. The neonate remained well for the first 2
      days of life. On the third day, he developed fever (39 degrees C) and poor
      peripheral circulation. On the fourth day, he developed petechiae and bruises
      over his chest wall and extremities, and prolonged bleeding was observed over
      venipuncture sites. Investigations revealed severe thrombocytopenia (platelets:
      41 x 10(9)/L) and a markedly deranged coagulation profile (prothrombin time: 19
      seconds [reference: < 10 seconds]; activated partial thromboplastin time: > 120
      seconds [reference: 24.2-37.0 seconds], serum D-dimers: 6722 ng/mL [reference: <
      500 ng/mL]), suggestive of disseminated intravascular coagulopathy. Clinical
      examination revealed yellow sclera, hepatomegaly (5 cm), and splenomegaly (2 cm),
      consistent with hepatitis. Serial chest radiographs showed bilateral pleural
      effusions, and an ultrasound of the abdomen demonstrated ascites. An
      echocardiogram showed normal cardiac structure and good contractility of both
      ventricles. However, a cranial ultrasound revealed bilateral grade 2
      intraventricular hemorrhages. Serum C-reactive protein increased to 33.9 mg/L.
      Liver-function tests were also markedly deranged at this time, with maximum
      values for serum alanine transferase, bilirubin, alkaline phosphatase, and
      ammonia concentration of 1354 IU/L, 258 micromol/L, 189 IU/L, and 147 micromol/L,
      respectively. Serum glucose levels were normal. Over the next 3 days, his fever
      subsided, and his liver function and clotting profile normalized by day 13 after
      onset of illness. A stool sample from the older brother, collected 14 days after
      his onset of illness at home, was positive for coxsackievirus B3 by both virus
      culture and enterovirus reverse-transcription polymerase chain reaction. He had
      neutralizing coxsackievirus B3 antibody titers of 1:2560 and 1:1280 on days 14
      and 28 after his onset of illness, respectively. No virus was cultured from the
      mother's stool sample, collected 5 days after her onset of illness, but the
      enterovirus polymerase chain reaction was positive and maternal sera neutralized
      the coxsackievirus B3 isolated from the neonate. The maternal sera also showed a
      more than fourfold rise in antibody titer from 1:80 to 1:640 on days 5 and 16
      after her onset of illness, respectively. Neonatal antibody titers also showed a
      more than fourfold rise from < 1:80 to 1:2560 on days 1 and 21 after his onset of
      illness, respectively. This demonstrates that both the mother and the neonate had
      had recent coxsackievirus B3 infections. Serially collected neonatal throat swab
      and stool samples were culture negative for enterovirus by 4 and 8 days after his
      onset of illness, respectively. However, enterovirus RNA remained detectable by
      reverse-transcription polymerase chain reaction in these samples for considerably
      longer, only becoming undetectable by 16, 23, and 41 days after his onset of
      illness. We show that even mild household infections may have potentially serious
      consequences for pregnant women and their infants.

PMID- 16908623
TI  - A dose-dependent requirement for the proline motif of CD28 in cellular and
      humoral immunity revealed by a targeted knockin mutant.
AB  - Activation of naive T cells requires the integration of signals through the
      antigen receptor and CD28. Although there is agreement on the importance of CD28,
      there remains controversy on the mechanism by which CD28 regulates T cell
      function. We have generated a gene-targeted knockin mouse expressing a mutation
      in the C-terminal proline-rich region of the cytoplasmic tail of CD28. Our
      analysis conclusively showed that this motif is essential for CD28-dependent
      regulation of interleukin 2 secretion and proliferation. In vivo analysis
      revealed that mutation of this motif-dissociated CD28-dependent regulation of
      cellular and humoral responses in an allergic airway inflammation model.
      Furthermore, we find an important gene dosage effect on the phenotype of the
      mutation and provide a mechanistic explanation for the conflicting data on the
      significance of this motif in CD28 function.

PMID- 16908624
TI  - Carbon monoxide reverses established pulmonary hypertension.
AB  - Pulmonary arterial hypertension (PAH) is an incurable disease characterized by a
      progressive increase in pulmonary vascular resistance leading to right heart
      failure. Carbon monoxide (CO) has emerged as a potently protective, homeostatic
      molecule that prevents the development of vascular disorders when administered
      prophylactically. The data presented in this paper demonstrate that CO can also
      act as a therapeutic (i.e., where exposure to CO is initiated after pathology is
      established). In three rodent models of PAH, a 1 hour/day exposure to CO reverses
      established PAH and right ventricular hypertrophy, restoring right ventricular
      and pulmonary arterial pressures, as well as the pulmonary vascular architecture,
      to near normal. The ability of CO to reverse PAH requires functional endothelial
      nitric oxide synthase (eNOS/NOS3) and NO generation, as indicated by the
      inability of CO to reverse chronic hypoxia-induced PAH in eNOS-deficient (nos3-/
      ) mice versus wild-type mice. The restorative function of CO was associated with
      a simultaneous increase in apoptosis and decrease in cellular proliferation of
      vascular smooth muscle cells, which was regulated in part by the endothelial
      cells in the hypertrophied vessels. In conclusion, these data demonstrate that CO
      reverses established PAH dependent on NO generation supporting the use of CO
      clinically to treat pulmonary hypertension.

PMID- 16908625
TI  - Enhancing immunogenicity by limiting susceptibility to lysosomal proteolysis.
AB  - T cells recognize protein antigens as short peptides processed and displayed by
      antigen-presenting cells. However, the mechanism of peptide selection is
      incompletely understood, and, consequently, the differences in the immunogenicity
      of protein antigens remain largely unpredictable and difficult to manipulate. In
      this paper we show that the susceptibility of protein antigens to lysosomal
      proteolysis plays an important role in determining immunogenicity in vivo. We
      compared the immunogenicity of proteins with the same sequence (same T cell
      epitopes) and structure (same B cell epitopes) but with different
      susceptibilities to lysosomal proteolysis. After immunizing mice with each of the
      proteins adsorbed onto aluminum hydroxide as adjuvant, we measured serum IgG
      responses as a physiological measure of the antigen's ability to be presented on
      major histocompatibility complex class II molecules and to prime CD4+ T cells in
      vivo. For two unrelated model antigens (RNase and horseradish peroxidase), we
      found that only the less digestible forms were immunogenic, inducing far more
      efficient T cell priming and antibody responses. These findings suggest that
      stability to lysosomal proteolysis may be an important factor in determining
      immunogenicity, with potential implications for vaccine design.

PMID- 16908626
TI  - Duration of the initial TCR stimulus controls the magnitude but not functionality
      of the CD8+ T cell response.
AB  - CD8+ T cells only require a brief stimulation with antigen in vitro to divide and
      differentiate into effector and memory cells upon transfer in vivo. The
      efficiency of clonal expansion and the functional characteristics of memory cells
      derived from briefly stimulated cells are poorly defined. We developed a system
      that allowed us to examine programming entirely in vivo. This was achieved by
      rapidly killing peptide-pulsed DCs carrying a diphtheria toxin receptor transgene
      with timed injections of diphtheria toxin without altering the course of an
      accompanying infection. The magnitude of clonal expansion, but not the
      functionality of the effector cells, correlated directly with the duration of
      antigen exposure. Furthermore, memory T cells were capable of mounting a
      secondary response, regardless of the length of antigen encounter during the
      primary response. These results indicate that the duration of initial antigen
      encounter influences the magnitude of the primary response, but does not program
      responsiveness during the secondary challenge.

PMID- 16908627
TI  - A garden of Notch-ly delights.
AB  - Over the past decade, the Notch signaling pathway has been shown to be crucially
      important for normal metazoan development and to be associated with several human
      inherited and late onset diseases. The realization that altered Notch signaling
      contributes at various levels to human disease lead in May to the first meeting
      dedicated solely to Notch signaling in vertebrate development and disease in
      Madrid, Spain. Hosted by the Cantoblanco Workshops on Biology and organized by
      Tom Gridley, Jose Luis de la Pompa and Juan Carlos Izpisua Belmonte, the meeting
      covered diverse aspects of this important signaling pathway.

PMID- 16908628
TI  - An oligodendrocyte-specific zinc-finger transcription regulator cooperates with
      Olig2 to promote oligodendrocyte differentiation.
AB  - Molecular mechanisms that control oligodendrocyte myelination during mammalian
      central nervous system (CNS) development are poorly understood. In this study, we
      identified Zfp488, an oligodendrocyte-specific zinc-finger transcription
      regulator, by screening for genes downregulated in the optic nerves of Olig1-null
      mice. The predicted primary structure of Zfp488 is evolutionarily conserved in
      vertebrates and invertebrates. In the developing CNS, Zfp488 is specifically
      expressed in oligodendrocytes but not their precursors. Its expression increases
      in parallel with that of major myelin genes Mbp and Plp1. Zfp488 is a nuclear
      protein that possesses transcriptional repression activity. In the developing
      chick neural tube, Zfp488 can promote oligodendrocyte precursor formation upon
      Notch activation. In addition, Zfp488 can interact and cooperate with the bHLH
      transcription factor Olig2 to promote precocious and ectopic oligodendrocyte
      differentiation. Furthermore, knockdown of Zfp488 via RNAi in an oligodendroglial
      cell line leads to the downregulation of myelin gene expression. Taken together,
      these data suggest that Zfp488 functions as an oligodendrocyte-specific
      transcription co-regulator important for oligodendrocyte maturation and that zinc
      finger/bHLH cooperation can serve as a mechanism for oligodendroglial
      differentiation.

PMID- 16908629
TI  - Differential regulation of gene expression in the digit forming area of the mouse
      limb bud by SHH and gremlin 1/FGF-mediated epithelial-mesenchymal signalling.
AB  - Spatially and temporally coordinated changes in gene expression are crucial to
      orderly progression of embryogenesis. We combine mouse genetics with experimental
      manipulation of signalling to analyze the kinetics by which the SHH morphogen and
      the BMP antagonist gremlin 1 (GREM1) control gene expression in the digit-forming
      mesenchyme of mouse limb buds. Although most mesenchymal cells respond rapidly to
      SHH signalling, the transcriptional upregulation of specific SHH target signals
      in the mesenchyme occurs with differential temporal kinetics and in a spatially
      restricted fashion. In particular, the expression of the BMP antagonist Grem1 is
      always upregulated in mesenchymal cells located distal to the SHH source and acts
      upstream of FGF signalling by the apical ectodermal ridge. GREM1/FGF-mediated
      feedback signalling is, in turn, required to propagate SHH and establish the
      presumptive digit expression domains of the Notch ligand jagged 1 (Jag1) and
      5'Hoxd genes in the distal limb bud mesenchyme. Their establishment is
      significantly delayed in Grem1-deficient limb buds and cannot be rescued by
      specific restoration of SHH signalling in mutant limb buds. This shows that
      GREM1/FGF feedback signalling is required for regulation of the temporal kinetics
      of the mesenchymal response to SHH signalling. Finally, inhibition of SHH signal
      transduction at distinct time points reveals the differential temporal dependence
      of Grem1, Jag1 and 5'Hoxd gene expression on SHH signalling. In particular, the
      expression of Hoxd13 depends on SHH signal transduction significantly longer than
      does Hoxd11 expression, revealing that the reverse co-linear establishment, but
      not maintenance of their presumptive digit expression domains, depends on SHH
      signalling.

PMID- 16908630
TI  - Distinct roles of the Pumilio and FBF translational repressors during C. elegans
      vulval development.
AB  - The C. elegans PUF and FBF proteins regulate various aspects of germline
      development by selectively binding to the 3' untranslated region of their target
      mRNAs and repressing translation. Here, we show that puf-8, fbf-1 and fbf-2 also
      act in the soma where they negatively regulate vulvaI development. Loss-of
      function mutations in puf-8 cause ectopic vulval differentiation when combined
      with mutations in negative regulators of the EGFR/RAS/MAPK pathway and suppress
      the vulvaless phenotype caused by mutations that reduce EGFR/RAS/MAPK signalling.
      PUF-8 acts cell-autonomously in the vulval cells to limit their temporal
      competence to respond to the extrinsic patterning signals. fbf-1 and fbf-2,
      however, redundantly inhibit primary vulval cell fate specification in two
      distinct pathways acting in the soma and in the germline. The FBFs thereby ensure
      that the inductive signal selects only one vulval precursor cell for the primary
      cell fate. Thus, translational repressors regulate various aspects of vulval cell
      fate specification, and they may play a conserved role in modulating signal
      transduction during animal development.

PMID- 16908631
TI  - Test duration for growth, feed intake, and feed efficiency in beef cattle using
      the GrowSafe System.
AB  - This study was conducted to determine the optimum test duration and the effect of
      missing data on accuracy of measuring feed efficiency and its 4 related traits
      ADG, DMI, feed conversion ratio, and residual feed intake in beef cattle using
      data from 456 steers with 5,397 weekly averaged feed intakes and BW repeated
      measurements taken over 91 d. Data were collected using the GrowSafe System at
      the University of Alberta Kinsella Research Station. The changes and relative
      changes in phenotypic residual variances and correlations (Pearson and Spearman)
      among data from shortened test durations (7, 14, 21, 28, 35, 42, 49, 56, 63, 70,
      77, or 84 d) and a 91-d test were used to determine the optimum test duration for
      the 4 traits. The traits were fitted to a mixed model with repeated measures
      using SAS. Test durations for ADG, DMI, feed conversion ratio, and residual feed
      intake could be shortened to 63, 35, 42, and 63 d, respectively, without
      significantly reducing the accuracy of the tests when BW was measured weekly. The
      accuracy of the test was not compromised when up to 30% of the records were
      randomly removed after the first 35 d on test. These results have valuable and
      practical implications for performance and feed efficiency testing in beef
      cattle.

PMID- 16908632
TI  - Genetic parameter estimates for serum insulin-like growth factor I
      concentrations, and body weight and weight gains in Angus beef cattle divergently
      selected for serum insulin-like growth factor I concentration.
AB  - Data for the current study were obtained from a divergent selection experiment in
      which the selection criterion was the average serum IGF-I concentrations of 3
      postweaning blood samples collected from purebred Angus calves. Multiple-trait
      derivative-free REML procedures were used to obtain genetic parameter estimates
      for IGF-I concentrations and for BW and BW gains measured from birth to the
      conclusion of a 140-d postweaning performance test. Included in the analysis were
      2,674 animals in the A(-1) matrix, 1,761 of which had valid records for IGF-I
      concentrations. Direct heritability estimates +/- SE for IGF-I concentration at d
      28, 42, and 56 of the postweaning period and for mean IGF-I concentrations were
      0.44 +/- 0.07, 0.51 +/- 0.08, 0.42 +/- 0.07, and 0.52 +/- 0.08, respectively.
      Heritability estimates for maternal genetic effects ranged from 0.10 +/- 0.05 to
      0.20 +/- 0.06. The proportion of total phenotypic variance due to the maternal
      permanent environmental effect was essentially zero for all measures of IGF-I
      concentrations. Genetic correlations of IGF-I concentrations with weaning and
      post-weaning BW ranged from 0.07 +/- 0.12 to 0.32 +/- 0.11 and generally
      demonstrated an increasing trend during the postweaning period. Averaged across
      the various measures of IGF-I, the genetic correlation of IGF-I with preweaning
      gain was 0.14, whereas the genetic correlation with postweaning gain was 0.29.
      Genetic correlations between IGF-I and BW gain were positive during all time
      intervals, except between weaning and the beginning of the postweaning test and
      from d 84 to 112 of the postweaning period. Environmental and phenotypic
      correlations of IGF-I with BW and BW gains were generally positive, but small.
      These results indicate that postweaning serum IGF-I concentration is moderately
      to highly heritable and has small positive genetic, environmental, and phenotypic
      correlations with BW other than birth weight and with pre- and postweaning gain.
      Therefore, if IGF-I proves to be a biological indicator of an economically
      important trait (e.g., efficiency of feed use for growth) in beef cattle, it
      should be possible to rapidly change IGF-I concentrations via selection without
      significantly altering live weight or rate of gain.

PMID- 16908633
TI  - Genetics of litter size in three maternal lines of rabbits: repeatability versus
      multiple-trait models.
AB  - Variance components were estimated in 3 lines of rabbits selected for litter size
      at weaning (A, Prat, and V) to test one of the assumptions of the models used for
      selection: that litter size data at different parities are repeated measurements
      of the same trait. Multiple-trait analyses were performed for the total number of
      kits born (TB), the number of kits born alive (BA), and the number of kits weaned
      (NW) per litter. Estimates were obtained by REML in multivariate analyses,
      including all of the information of the selection criteria, under a repeatability
      model or a multiple-trait model, considering litter size at the first, second,
      and subsequent parities as different traits. Models included the fixed effects of
      the physiological status of the female and the year-season of mating day, buck
      and doe random permanent environmental effects, and doe additive genetic effects.
      Results indicated that prolificacy was determined mainly by doe components and
      that the service sire had a very small effect. Heritabilities for the first and
      second parities were greater than the estimates obtained under the repeatability
      model (0.04 to 0.14 for the repeatability model). In the A and V lines, similar
      values of heritability were found at the first and second parities, but in the
      Prat line heritability at the second parity was always greater than at the first
      and greater parities (values of 0.21, 0.17, and 0.15 for TB, BA, and NW,
      respectively, in second parities of the Prat line). Genetic correlations between
      the same traits at different parities were approximately 0.8 for all traits in
      line A, but much lower in the other 2 lines. On average, the values were 0.64 for
      TB, 0.48 for BA, and 0.39 for NW between the first and second parities, and 0.65
      for TB, 0.56 for BA, and 0.45 for NW between the first and third and greater
      parities. Genetic correlations between the second and greater parities showed the
      greatest values (approximately 0.8) in lines A and Prat for all traits, but they
      were lower in line V (0.63 for BA and 0.37 for NW). The heterogeneity of
      heritabilities and genetic correlations between parities lower than 0.9 suggests
      that litter size at different parities could be considered as different traits
      when genetic evaluations are performed. However, when the accuracies of predicted
      breeding values under a multiple-trait and a repeatability model were calculated,
      assuming the first to be the true model, the values obtained were nearly the same
      for all traits in all lines.

PMID- 16908634
TI  - Board-invited review: intrauterine growth retardation: implications for the
      animal sciences.
AB  - Intrauterine growth retardation (IUGR), defined as impaired growth and
      development of the mammalian embryo/fetus or its organs during pregnancy, is a
      major concern in domestic animal production. Fetal growth restriction reduces
      neonatal survival, has a permanent stunting effect on postnatal growth and the
      efficiency of feed/forage utilization in offspring, negatively affects whole body
      composition and meat quality, and impairs long-term health and athletic
      performance. Knowledge of the underlying mechanisms has important implications
      for the prevention of IUGR and is crucial for enhancing the efficiency of
      livestock production and animal health. Fetal growth within the uterus is a
      complex biological event influenced by genetic, epigenetic, and environmental
      factors, as well as maternal maturity. These factors impact on the size and
      functional capacity of the placenta, uteroplacental blood flows, transfer of
      nutrients and oxygen from mother to fetus, conceptus nutrient availability, the
      endocrine milieu, and metabolic pathways. Alterations in fetal nutrition and
      endocrine status may result in developmental adaptations that permanently change
      the structure, physiology, metabolism, and postnatal growth of the offspring.
      Impaired placental syntheses of nitric oxide (a major vasodilator and angiogenic
      factor) and polyamines (key regulators of DNA and protein synthesis) may provide
      a unified explanation for the etiology of IUGR in response to maternal
      undernutrition and overnutrition. There is growing evidence that maternal
      nutritional status can alter the epigenetic state (stable alterations of gene
      expression through DNA methylation and histone modifications) of the fetal
      genome. This may provide a molecular mechanism for the role of maternal nutrition
      on fetal programming and genomic imprinting. Innovative interdisciplinary
      research in the areas of nutrition, reproductive physiology, and vascular biology
      will play an important role in designing the next generation of nutrient-balanced
      gestation diets and developing new tools for livestock management that will
      enhance the efficiency of animal production and improve animal well being.

PMID- 16908635
TI  - Changes in fetal organ weights during gestation after selection for ovulation
      rate and uterine capacity in swine.
AB  - We hypothesized that the ability of the fetus to alter nutrient shunting and
      organ growth might be associated with uterine capacity. White crossbred gilts
      from a randomly selected control line, a line selected for ovulation rate, and a
      line selected for uterine capacity (UC) were unilaterally hysterectomized
      ovariectomized at 160 d of age, mated at estrus, and slaughtered at 45, 65, 85,
      and 105 d of gestation (9 to 18 gilts for each line x day combination). Analysis
      of the data revealed that heart weights and fetal weights were decreased in the
      ovulation rate line. No significant differences were obtained in fetal,
      placental, or fetal organ weights between the control and UC lines. Allometric
      growth of organs was assessed by examination of the slopes of the relationships
      between fetal weights and fetal organ weights after natural log transformation.
      Only the relative growth of the liver differed between selection lines and was
      greater (P = 0.01) in the UC compared with the control line during early
      pregnancy (d 45 and 65). Allometric growth of the fetal brain, liver, and heart
      differed with day of gestation. A brain-sparing effect was greater (P < 0.01) on
      d 85 and 105 compared with d 45 and 65. By contrast, a heart-sparing effect was
      present during early gestation and disappeared in later gestation. Fetal liver
      weights were hypersensitive to differences in fetal weights on d 45, possibly
      associated with placental effects on fetal liver weight. Fetal spleen weights
      were proportional to fetal weights throughout gestation. These results indicate
      that selection for ovulation rate decreased total fetal and fetal heart weights,
      and that selection for UC altered the relationship between total fetal and fetal
      liver weights during early gestation. Results further indicate significant
      changes in allometric growth of organs during gestation.

PMID- 16908636
TI  - Effects of suckling intensity on milk yield and piglet growth from lactation
      enhanced gilts.
AB  - The effects of suckling intensity on milk yield and piglet growth were determined
      when lactation capacity of the sow was enhanced through overexpression of a
      mammary-specific transgene, bovine alpha-lactalbumin. Lactational response to
      increased suckling stimulation was determined by fostering litters of the same
      age (d 1) or 7 d older (d 7) than the day of lactation to sows nontransgenic
      (control) or transgenic (TG) for bovine alpha-lactalbumin. Twenty first-parity
      gilts were allocated to 4 treatments dependent on gilt genotype and age of litter
      fostered (control d 1, control d 7, TG d 1, and TG d 7). Litters were
      standardized to 10 piglets within 24 h postpartum, and nonbirth piglets were
      fostered to gilts with an equal litter BW within age groups at 36 h postpartum.
      Milk yield was determined by the weigh-suckle-weigh method on d 6, 9, 12, 15, and
      18 of lactation. Mean daily milk yield was greater (P = 0.031) for TG gilts
      compared with control gilts and tended to be greater (P = 0.056) for all gilts
      with d-7 piglets compared with those with d-1 piglets. Daily milk yield of TG d 7
      gilts increased rapidly to peak at d 9 and was greater than milk yield of all
      control gilts at d 9 (P < 0.01), 12 (P < 0.02), and 15 (P < 0.02). Mean daily
      milk yield of TG d 7 gilts was 2.1 kg greater (P = 0.002) than for control d 7
      gilts and 2.0 kg greater (P = 0.004) than for TG d 1 gilts. Daily milk yield of
      control d 1 gilts was not different from that of TG d 1 gilts (P = 0.49) or
      control d 7 gilts (P = 0.63). Piglet BW gain between d 3 and 6 was greater (P <
      0.01) in the TG d 7 group than for all other groups and was greater (P < 0.05)
      than the control groups between d 6 and 9. No difference was found when comparing
      accumulated BW gain of the piglets between the day of age at foster (d 1 vs. 7; P
      = 0.606) or between the control d 1 and control d 7 groups (P = 0.759).
      Accumulated BW gain of piglets suckling TG d 7 gilts from d 3 through 9 was
      greater (P < 0.02) than that of the other groups and continued to be greater (P <
      0.05) than that of either of the control groups through d 15. However, by d 15,
      accumulated BW gain of piglets suckling TG d 1 gilts was no longer different (P =
      0.40) from that of the TG d 7 group and was greater (P < 0.05) than that of the
      control d 1 group. The enhanced lactation potential of these TG gilts synergized
      with suckling intensity to stimulate increased milk production during early
      lactation, resulting in increased piglet growth.

PMID- 16908637
TI  - Supplemental vitamin C and yeast cell wall beta-glucan as growth enhancers in
      newborn pigs and as immunomodulators after an endotoxin challenge after weaning.
AB  - To test possible dietary immune modulators, 32 crossbred male pigs were given 1
      of 4 dietary treatments (8 pigs/treatment): control, Saccharomyces cerevisiae
      with beta-glucan (Energy Plus, Natural Chem Industries LTD, Houston, TX; 0.312
      g/kg of BW, 2.5% of diet), vitamin C (Stay C 35, DSM Nutritional Products Inc.,
      Prisippany, NJ; 75 ppm), or beta-glucan plus vitamin C together (combination;
      0.312 g/kg of BW and 75 ppm, respectively). Supplements were given in whole milk
      within 36 h of birth and then daily for 2 wk until weaning, when the supplement
      was given in feed for an additional 2 wk. Growth was recorded during the 4 wk of
      supplement delivery. An i.v. lipopolysaccharide challenge (LPS; 150 microg/kg)
      was given 14 d postweaning at 0900. Behavior was observed, and blood samples were
      collected every 30 min for 4 h via a jugular catheter from -1 (0800) to 3 (1200)
      h relative to challenge (-60, -30, 0, 30, 60, 90, 120, 150, and 180 min), and
      tissues were collected after exsanguination. Beta-glucan (glucan and combination)
      increased (P < 0.05) BW and ADG compared with vitamin C and control. Cortisol
      concentrations showed an interaction (P < 0.05) of the beta-glucan and vitamin C.
      Intestinal expression of tumor-necrosis factor (TNF)-alpha mRNA was greatest for
      vitamin C and beta-glucan compared with control and combination, and liver TNF
      alpha mRNA expression showed a main effect (P < 0.01) of beta-glucan. Lung
      expression of TNF-alpha mRNA exhibited a vitamin C effect (P < 0.01). In
      contrast, spleen had greater (P < 0.01) relative abundance of TNF-alpha mRNA in
      beta-glucan pigs. Intestinal expression of IL-1Ra mRNA was greater (P < 0.05) for
      vitamin C and beta-glucan treatments compared with the control and combination
      pigs. Liver expression of IL-1 receptor antagonist mRNA exhibited a vitamin C
      effect (P < 0.01). Lying and sleeping behaviors differed (P < 0.05) among
      treatments early in the observations (0700 to 0720), then sporadically until 50
      min after the LPS injection. The vitamin C group slept less (P < 0.05) on those
      occasions. The time spent lying was least (P < 0.05) for the glucan and
      combination pigs immediately after the injection. These results show a complex
      interaction between vitamin C and this yeast product after LPS challenge, with
      differential expression in tissues by 2 h after LPS injections. The combination
      enhanced postweaning growth and reduced TNF-alpha expression of the intestinal
      and liver tissues, suggesting an important immunomodulatory role of the
      combination treatment.

PMID- 16908638
TI  - Effects of feeding grains naturally contaminated with Fusarium mycotoxins with
      and without a polymeric glucomannan mycotoxin adsorbent on reproductive
      performance and serum chemistry of pregnant gilts.
AB  - Contamination of animal feedstuffs with Fusarium mycotoxins can cause reduced
      feed intake and hyperaminoacidemia resulting from reduced hepatic protein
      synthesis. The current study investigated the effects of feeding grains naturally
      contaminated with Fusarium mycotoxins on reproductive performance, serum
      chemistry, ADFI, and ADG of gilts, and tested the ability of a polymeric
      glucomannan mycotoxin adsorbent (GMA) to reduce or eliminate the effects of the
      contaminated feeds. Thirty-six Yorkshire gilts were fed 3 diets (n = 12
      gilts/diet) from 91 +/- 3 d of gestation until farrowing. Diets included 1)
      control, 2) contaminated grains, and 3) contaminated grains + 0.2% GMA. Diets
      contaminated with Fusarium mycotoxins did not affect ADFI (P = 0.24), but ADG (P
      = 0.029) and G:F (P = 0.047) were reduced. Serum concentrations of beta
      hydroxybutyrate, haptoglobin, protein, albumin, globulin, urea, glucose,
      cholesterol, Ca, Na, Mg, P, K, and Cl, and hepatic enzyme activities were not
      affected by diet. The frequency of stillborn piglets was greater (P = 0.03) for
      gilts fed contaminated grains compared with that of gilts fed contaminated grains
      + GMA. The feeding of contaminated grains + GMA also increased (P = 0.026) the
      percentage of pigs born alive compared with gilts fed the contaminated diets. In
      conclusion, feeding gilts diets that are naturally contaminated with Fusarium
      mycotoxins can increase the incidence of stillborn piglets and this effect can be
      reduced by dietary supplementation with GMA.

PMID- 16908639
TI  - Effects of cyadox and olaquindox on intestinal mucosal immunity and on fecal
      shedding of Escherichia coli in piglets.
AB  - A 2 x 3 factorial arrangement of treatments was used to determine the effects of
      olaquindox and cyadox on the intestinal mucosal immune response and on fecal
      shedding of Escherichia coli in Landrace x Large White barrows that had been
      orally given 10(10) cfu of E. coli (O139:K88). Factors included 1) E. coli
      inoculation or no inoculation, and 2) no antimicrobial, 100 mg of olaquindox/kg,
      and 100 mg of cyadox/kg in the basal diet, respectively. The effects of cyadox
      and olaquindox were assessed in terms of fecal shedding of E. coli, the number of
      intraepithelial lymphocytes (IEL), immunoglobulin A-positive cells (APC) in the
      intestinal lamina propria, and ADG. There was no difference in the fecal shedding
      of total E. coli or the inoculated E. coli between olaquindox-supplemented pigs
      and cyadox-supplemented pigs during the experiment. However, fecal shedding of
      the inoculated E. coli in olaquindox- or cyadox-supplemented pigs was less (P <
      0.05) than that in nonsupplemented pigs. Escherichia coli inoculation increased
      IEL and APC in the jejunum and ileum, but olaquindox or cyadox decreased IEL and
      APC (P < 0.05). Jejunal APC in cyadox-supplemented pigs was less (P < 0.05) than
      that in olaquindox-supplemented pigs. Escherichia coli inoculation reduced (P <
      0.05) ADG, whereas the supplementations improved ADG (P < 0.01) during the
      experiment. Average daily gain in cyadox-supplemented pigs was greater (P < 0.05)
      than that in olaquindox-supplemented pigs. The data indicated that olaquindox and
      cyadox reduced the number of intestinal E. coli and suppressed E. coli-induced
      immune activation, which might be responsible for the enhanced growth that was
      observed.

PMID- 16908640
TI  - Effects of beta-glucan extracted from Saccharomyces cerevisiae on growth
      performance, and immunological and somatotropic responses of pigs challenged with
      Escherichia coli lipopolysaccharide.
AB  - Three experiments were conducted to investigate the effects of beta-glucan
      supplementation on pig performance and immune function. In Exp. 1, 100 weaned
      pigs (8.65 +/- 0.42 kg of BW and 28 +/- 2 d of age) were used in a 35-d
      experiment to determine the effects of graded levels of beta-glucan. Pigs were
      randomly allotted to 1 of 5 treatments containing beta-glucan supplemented at 0,
      25, 50, 100, or 200 ppm. Each treatment was replicated using 5 pens containing 4
      pigs per pen. The ADG of pigs between d 14 to 28 and d 0 to 28 responded to
      dietary beta-glucan in a quadratic fashion (P < 0.05), whereas beta-glucan had no
      effect on ADFI and G:F in any period. In Exp. 2, 80 crossbred pigs (8.23 +/- 0.56
      kg of BW and 28 +/- 2 d of age) were used in a 35-d experiment. Pigs were
      allotted to 1 of 2 dietary treatments (0 or 50 ppm of beta-glucan in the diet)
      using 10 pens with 4 pigs per pen. Pigs treated with beta-glucan had greater ADG
      in the 14- to 28-d (P = 0.05) and 0-to 28-d (P = 0.035) periods. The ADFI of pigs
      receiving beta-glucan was increased (P < 0.05) in the periods from 0 to 14, 0 to
      28, and 28 to 35 d. The lymphocyte proliferation index in response to
      phytohemagglutinin (P = 0.051) and concanavalin A (P = 0.052) tended to decrease
      on d 14 in pigs supplemented with beta-glucan compared with pigs without
      supplementation. In Exp. 3, 24 barrows (8.89 +/- 0.20 kg of BW and 28 d of age)
      were used to investigate the immunological and somatotropic responses of pigs
      challenged with lipopolysaccharide (LPS). Experimental treatments were arranged
      in a 2 x 2 factorial, with the main effects of LPS challenge (saline vs. LPS) and
      dietary addition of beta-glucan (0 vs. 50 ppm). Pigs were raised individually in
      metabolic cages. Pigs were fed 0 or 50 ppm of beta-glucan for 28 d and then
      challenged with LPS (25 microg/kg of BW) or saline. After LPS injection, blood
      was obtained at 0, 1.5, 3, 4.5, 6, and 7.5 h to determine cytokine production and
      the somatotropic response. Dietary beta-glucan increased plasma interleukin-6 at
      1.5, 3, and 4.5 h and tumor necrosis factor-alpha at 3 and 4.5 h and increased
      plasma interleukin-10 from 3 to 7.5 h after LPS challenge. The beta-glucan
      treatments had no effect on growth hormone. In conclusion, beta-glucan can
      selectively influence performance and partially offer benefits on somatotropic
      axis and immune function in weaned piglets challenged with LPS.

PMID- 16908641
TI  - Effect of selenium intake and fetal age on mRNA levels of two selenoproteins in
      porcine fetal and maternal liver.
AB  - The objective of this study was to determine if levels of mRNA encoding cytosolic
      glutathione peroxidase (cGPx) and thioredoxin reductase (TrxR-1) change during
      fetal development, and if maternal Se intake during gestation affects the mRNA
      levels of these proteins. Prepubertal gilts (n = 24) were randomly assigned to
      either Se-adequate (0.39 ppm of Se; n = 12) or Se-deficient (0.05 ppm of Se; n =
      12) diets, 6 wk before breeding. Maternal liver was collected at d 10, 45, 70,
      and 114 of pregnancy, and fetal liver samples were collected at the same times
      except d 10. Complementary DNA sequences encoding cGPx and TrxR-1 were cloned and
      sequenced. Quantitative real-time PCR analysis indicated that levels of mRNA for
      cGPx in fetal liver decreased more than 3-fold between d 45 and 114 of gestation.
      Although the gilts were only marginally deficient in Se, and maternal Se intake
      did not affect cGPx mRNA levels in fetal liver, the low-Se diet tended (P = 0.1)
      to reduce fetal TrxR-1 mRNA levels. In the liver of the dams, the low Se intake
      did not affect mRNA levels for either cGPx or TrxR-1. Compared with the liver of
      the dams, mRNA levels for cGPx were about 3.5 times lower in fetal liver. Results
      of this study support the hypothesis that neonatal pigs are born with reduced
      cGPx corresponding to reduced cGPx mRNA levels during late gestation.

PMID- 16908642
TI  - Meal size and feeding frequency influence serum leptin concentration in yearling
      horses.
AB  - Energy is an essential nutrient for all horses, and it is especially important in
      performance horses, pregnant and lactating mares, and young growing horses. A
      negative energy balance in horses such as these may result in unsatisfactory
      performance, decreased fertility, or slow growth. Therefore, ensuring adequate
      energy intake is an important aspect of the nutritional management of the equine.
      This study was undertaken to investigate the effects of feeding large,
      carbohydrate-rich, concentrate meals on the satiety-inducing hormone, leptin.
      Three groups of yearling horses were rotated through 3 feeding schedules in a
      replicated 3x3 Latin square design. Horses were fed 2, 3, or 4 times per day (2x,
      3x, and 4xfeeding schedules, respectively), each for a period of 11 d, with the
      total amount of daily feed held constant. Horses were weighed and BCS was
      determined on the first day of each period. Blood samples were collected before
      the morning meal on d 1, 4, and 7 of each period. Additionally, blood was sampled
      for the last 24 h of the 2xand 4xdietary periods. Neither weight nor BCS changed
      during the study (P = 0.99 and P = 0.28, respectively). Both mean and peak plasma
      glucose were greatest in 2xhorses (P < 0.05), as were mean areas under the curve.
      Serum leptin concentration increased in 2xhorses (P < 0.05), but not in horses
      fed 3 or 4 times daily. Leptin was elevated in horses with greater BCS (P < 0.05)
      and increased steadily throughout the study (P < 0.05). Data from the 24-h
      collection indicated that 2xhorses had fluctuations in leptin production
      throughout the day (P < 0.05), whereas horses fed 4 times daily did not. Overall,
      this study indicates that feeding horses 2 large concentrate meals daily can
      increase mean serum leptin concentrations and may cause fluctuations in leptin
      production over a 24-h period. This departure from baseline leptin concentration
      has the potential to affect appetite, along with numerous other physiological
      processes.

PMID- 16908643
TI  - Evaluation of milk somatic cells as a source of mRNA for study of lipogenesis in
      the mammary gland of lactating beef cows supplemented with dietary high-linoleate
      safflower seeds.
AB  - Our objectives were 2-fold: to determine the effect of dietary linoleate on milk
      fat composition and on transcript abundance of acetyl-CoA carboxylase (ACC),
      fatty acid synthase (FAS), lipoprotein lipase (LPL), and stearoyl-CoA desaturase
      (SCD) mRNA in mammary tissue, and to evaluate milk somatic cell mRNA as a source
      of mammary tissue mRNA for these enzymes. Eighteen primiparous, crossbred beef
      cows (BW = 411 +/- 24 kg; BCS = 5.25) were offered Foxtail millet hay at 1.68% of
      BW daily and either a low-fat control (n = 9) or a high-linoleate (79% 18:2n-6),
      cracked safflower seed supplement (n = 9). Diets were isonitrogenous and
      isocaloric, and the linoleate diet contained 5.4% of DMI as fat. At slaughter (37
      +/- 3 d postpartum), mammary tissue was sampled and immediately frozen in liquid
      N2 before being stored at -80 degrees C. Milk samples were obtained from the same
      mammary glands and immediately centrifuged at 1,200 x g to pellet somatic cells.
      A ribonuclease protection assay was used to quantify the mRNA in the mammary
      gland and milk somatic cells. Effects of diet, tissue, or their interaction were
      not observed for ACC (P = 0.28, 0.89, and 0.35, respectively), FAS (P = 0.38,
      0.66, and 0.20, respectively), LPL (P = 0.09, 0.15, and 0.43, respectively), or
      SCD (P = 0.45, 0.19, and 0.29, respectively). Dietary effects on fatty acid
      profile of the milk fat suggested that linoleate supplementation might have
      decreased de novo lipogenesis while increasing uptake of dietary fatty acids;
      this effect was consistent with a trend toward greater LPL mRNA for linoleate-fed
      cows (P = 0.09). Correlations (r values) between mammary tissue and milk somatic
      cell data for each mRNA for the low-fat control diet were: ACC, 0.76 (P = 0.02);
      FAS, 0.69 (P = 0.04); LPL, 0.68 (P = 0.04); and SCD, 0.73 (P = 0.05), and for the
      linoleate diet were: ACC, 0.85 (P = 0.003); FAS, 0.75 (P = 0.02); LPL, 0.90 (P =
      0.001); and SCD, 0.73 (P = 0.03). We conclude that milk somatic cells obtained
      from lactating beef cows can be used as a source of RNA to study nutritional
      regulation of mammary gland lipogenesis in cows fed dietary fat supplements.

PMID- 16908644
TI  - Chlortetracycline supplementation of yearling dairy heifers.
AB  - Chlortetracycline is an antibiotic that is used to increase weight gain,
      efficiency of gain, carcass grade, and conception rates. The objective of this
      experiment was to evaluate the effects of supplementation of 350 mg/d of
      chlortetracycline on ADG, G:F, BCS, thyroxine, and systemic glucose
      concentrations in yearling dairy heifers. Forty 12-mo-old Holstein heifers
      (initial BW = 363 +/- 21 kg) were housed in a free-stall barn with ad libitum
      access to feed and water for 104 d. A transition period was begun 14 d before the
      age of 12 mo to acclimate the heifers to the diet. The chlortetracycline-fed
      group (n = 20) consumed 328 +/- 8.2 mg of chlortetracycline/heifer daily.
      Measurements for BW, withers and hip heights, BCS, and health score were recorded
      weekly. Dry matter intake was measured daily. Blood was sampled every 4 d to
      determine plasma thyroxine and glucose concentrations and every 2 d to determine
      progesterone concentrations. Heifers were artificially inseminated on the first
      observed standing heat after 13 mo of age. There were no effects of
      chlortetracycline on ADG, G:F, withers and hip heights, BCS, blood glucose
      concentrations, peak progesterone concentrations, health, or conception rate.
      There was an interaction between treatment and time for chlortetracycline on
      serum thyroxine concentration. In the beginning of the experiment, serum
      thyroxine concentration was lower in heifers supplemented with chlortetracycline.
      There was no difference between treatments in thyroxine concentration at the end
      of the experiment. Chlortetracycline supplementation was not beneficial for
      yearling dairy heifers.

PMID- 16908645
TI  - Effects of interval-feeding whole sunflower seeds during mid to late gestation on
      performance of beef cows and their progeny.
AB  - This experiment was conducted to determine the effects of interval feeding of
      whole sunflower seeds on the performance of beef cows and their progeny. During
      mid to late gestation, 144 multiparous, spring-calving beef cows (588 kg of
      initial BW; 5.6 initial BCS; 4 to 13 yr old) were individually fed 1 of 3
      supplements 4 d/wk for a 76-d period. Supplements (DM basis) included: 1) 0.68 kg
      of soybean meal/feeding (NCON); 2) 3.01 kg of a soybean hull-based
      supplement/feeding (PCON); and 3) 1.66 kg of whole sunflower seeds high in
      linoleic acid/feeding (WSUN). Supplements were formulated to provide similar
      amounts of CP and ruminally degraded intake protein; PCON and WSUN were also
      formulated to be isocaloric. During the supplementation period, cows had free
      choice access to bermudagrass (Cynodon dactylon) and tall-grass prairie hay. By
      the end of the 76-d supplementation period, cows fed PCON (P < 0.01) and NCON (P
      < 0.01) had gained more BW than cows fed WSUN (33, 23, and 10 kg, respectively).
      However, from the end of this supplementation period to the beginning of the
      breeding season 84 d later, cows supplemented with PCON had lost more (P < 0.01)
      BW than cows supplemented with WSUN (-123 kg vs. -111 kg). Cow BW change through
      weaning (-50 kg, P = 0.43) and final cow BW (536 kg, P = 0.70) at weaning were
      not different among supplement groups. Furthermore, cow BCS was similar among
      supplement treatment groups at the end of the supplementation period (5.3, P =
      0.09), at the beginning of the breeding season (4.8, P = 0.38), and at weaning
      (4.7, P = 0.08). No difference among treatments was detected for calf birth
      weight (36 kg, P = 0.42), calf weaning weight (235 kg, P = 0.67), percentage of
      cows exhibiting luteal activity at the beginning of the breeding season (57%, P =
      0.29), or pregnancy rate (88%, P = 0.44). However, first service conception rate
      was greater (P = 0.01) for cows fed PCON (79%) and tended (P = 0.07) to be
      greater for cows fed WSUN (74%) than for cows fed NCON (53%). After weaning, all
      steer calves were placed in a feedlot and fed a high-concentrate finishing diet
      for an average of 188 d. Supplements fed to dams during gestation did not
      influence feedlot performance or carcass characteristics. Prepartum energy
      supplementation, regardless of energy source or prepartum energy balance,
      resulted in improved conception rate, but other measures of reproduction, calf
      and feedlot performance, and carcass characteristics were not affected.

PMID- 16908646
TI  - Effect of refined soy oil or whole soybeans on intake, methane output, and
      performance of young bulls.
AB  - An experiment was conducted to establish the effects of feeding refined soy oil
      (RSO) or whole soybeans (WSB) containing soy oil on DMI, animal performance, and
      enteric methane (CH4) emissions in young bulls. Thirty-six Charolais and Limousin
      cross-bred, young beef bulls (338 +/- 27 kg of BW, 218 +/- 17 d of age at the
      beginning of the experiment) were blocked by BW, age, and breed before being
      assigned in a randomized complete block design to 1 of 3 experimental treatments
      (n = 12). The experimental period lasted for 103 d, with enteric CH4 output
      recorded for 2 periods of 5 consecutive days on d 37 to 41 and d 79 to 83. The 3
      dietary treatments consisted of a barley/soybean meal-based concentrate with 0
      g/d of RSO; oil from WSB as 6% of DMI (WSB treatment); and oil from RSO as 6% of
      DMI (RSO treatment). Each diet had a 10:90 forage:concentrate ratio, using barley
      straw as the forage source. Diet affected DMI (P < or = 0.001) and GE intake (P <
      0.05 during the CH4 measurement periods), with the WSB treatment producing the
      lowest values. The addition of WSB decreased ADG (P < 0.05) compared with the RSO
      treatment. The WSB treatment also decreased (P < 0.05) average daily carcass gain
      (ADCG). Both the RSO and WSB concentrates decreased (P < 0.05 to P < 0.001) daily
      enteric CH4 output when expressed in terms of liters per day, liters per kilogram
      of DMI, percentage of GE intake, liters per kilogram of ADG, and liters per
      kilogram of ADCG. Diet had no effect (P = 0.557) on ruminal protozoal numbers.
      The reductions in enteric CH4 were achieved at relatively high oil inclusion
      levels. Such oil levels have previously been reported to decrease DMI of high
      forage diets, although no effect on DMI was noted with the low-forage diets fed
      in this experiment. This impact on DMI of high-forage diets may limit the range
      of diets for which this CH4 reduction strategy may be applicable. The inclusion
      level of WSB in the current experiment (27%) was beyond the palatability
      threshold of the bulls used and resulted in a marked decline in intake and
      performance. Therefore, WSB may have a role to play in ruminant diets, but only
      at a reduced inclusion rate.

PMID- 16908647
TI  - Effects of adding poultry fat in the finishing diet of steers on performance,
      carcass characteristics, sensory traits, and fatty acid profiles.
AB  - Use of poultry fat in the finishing diets of steers has not been studied as a
      potential source of added energy. Therefore, 60 Angus crossbred steers were fed 1
      of 3 dietary treatments consisting of 1) a corn-soybean meal control diet devoid
      of added fat; 2) the control diet formulated with 4% tallow; or 3) the control
      diet formulated with 4% poultry fat. Addition of fat did not (P = 0.17) affect
      ADG for the 112-d study. The inclusion of tallow in the diet reduced (P < 0.05)
      ADFI of steers compared with those on the control diet; however, ADFI of steers
      fed poultry fat did not differ from those fed the control (P = 0.06) or the
      tallow (P = 0.36) diets. At d 55, steers consuming either fat source had improved
      (P < 0.05) G:F compared with steers fed the control diet. For the entire 112 d,
      steers consuming the poultry fat diet gained more efficiently (P < 0.05) than the
      control steers, and the tallow-fed steers were intermediate and not different
      from the other groups (P > or = 0.14). The inclusion of fat in the diet did not
      (P > or = 0.15) affect carcass characteristics. Steaks from the steers consuming
      diets with added fat were darker (lower L* value; P < 0.05) than the controls;
      however, dietary treatments did not (P > or = 0.10) affect any other objective
      color measurements or discoloration scores during retail display. Thiobarbituric
      acid reactive substances for LM steaks did not differ (P = 0.21) by dietary
      treatment. The cooked LM steaks from steers fed poultry fat did not (P > or =
      0.80) differ in juiciness or flavor intensity from steaks of steers fed the
      control or tallow diets. There were also no differences (P = 0.18) in off flavors
      as a result of added dietary fat. In the LM and adipose tissue, percentages of
      total SFA were increased (P = 0.05) by adding supplemental fat to the diet,
      regardless of source. In the LM, total MUFA were decreased (P = 0.02) by adding
      supplemental fat. Conversely, diet did not (P > or = 0.14) affect the proportions
      of total PUFA in either tissue or total MUFA in the adipose tissue. Results
      indicated that replacing beef tallow in finishing diets with poultry fat, a more
      economical energy source, had no detrimental effects on growth performance,
      carcass characteristics, retail display life, fatty acid profiles, or
      palatability.

PMID- 16908648
TI  - Influence of rearing conditions on performance, behavioral, and physiological
      responses of pigs to preslaughter handling, carcass traits, and meat quality.
AB  - A total of 120 crossbred [synthetic line x (Large White x Landrace)] pigs
      (castrated males and females) were used to evaluate the influence of rearing
      conditions for growing-finishing pigs on growth performance, carcass, stress
      reactions at slaughter, and meat eating quality. At approximately 35 kg of live
      weight (LW), littermates were allocated to either a conventional (fully slatted
      floor, 0.65 m2/pig, considered as control, CON) or an alternative (sawdust
      bedding with free access to an outdoor area, 2.4 m2/pig, OUT) system, until
      slaughter at approximately 110 kg of LW. Pigs had free access to standard growing
      and finishing diets. The trials were conducted in spring, summer, and winter,
      with each season involving 2 pens of 10 pigs in each system. Compared with the
      CON, the OUT pigs exhibited a greater growth rate (+10%, P < 0.001) due to their
      greater feed intake (+0.23 kg/d, P < 0.01), resulting in a greater body weight at
      slaughter (+7 kg, P < 0.001). The OUT pigs had thicker backfat (+2.4 mm, P <
      0.01) and lower lean meat content (- 2.0% points, P < 0.001) than the CON pigs.
      The OUT system did not (P > 0.10) influence the behavioral activities of pigs
      during lairage at the slaughterhouse, or the urinary levels of catecholamines and
      cortisol, and plasma levels of ACTH, cortisol, lactate, creatine kinase, and FFA
      immediately after slaughter. The OUT pigs had similar (P > 0.10) pH values 30 min
      postmortem (pH1) in the LM, biceps femoris (BF), and semimembranosus (SM)
      muscles, similar ultimate pH (pHu) in LM, but lower pHu in SM (- 0.07 unit, P <
      0.001) and in BF (- 0.03 unit, P = 0.029). Despite nonsignificant effects of
      production system on stress reactions at slaughter, assessed by urine and plasma
      indicators and muscle metabolism at 30 min postmortem, meat from OUT pigs had
      more LM drip loss after 2 (+1.0%, P = 0.003) and 4 (+1.1%, P = 0.010) d than did
      meat from the CON pigs. The OUT system slightly increased meat yellowness (b*
      value) in the LM (+0.7 unit, P = 0.001), BF (+0.5 unit, P = 0.014), and SM (+0.5,
      unit P = 0.041), whereas redness (a*) and lightness (L*) of the 3 muscles were
      unaffected (P > 0.07). Intramuscular fat content was greater in the LM (+17%, P =
      0.001), BF (+14%, P = 0.004), and SM (+17%, P = 0.003) of the OUT pigs. Outdoor
      rearing during summer and winter improved meat juiciness, whereas odor, flavor,
      and tenderness were unaffected (P > 0.10). Influence of rearing conditions on all
      the other traits studied did not depend on the season.

PMID- 16908649
TI  - Modified-atmosphere storage under subatmospheric pressure and beef quality: I.
      Microbiological effects.
AB  - The microflora was studied in beef stored in stainless steel containers kept
      under reduced pressure (20 to 30 kPa) in a modified atmosphere (70% N2 + 30% CO2
      or pure CO2) at 3 to 4 degrees C and 0 to 1 degrees C at a headspace:meat volume
      ratio of 2:1. Samples were obtained at weekly intervals, 1 to 3 times. Total
      colony counts (TCC) for Pseudomonas spp. and Brochothrix thermosphacta were
      generally 1 to 2 log10 cfu greater than in the control group of vacuum-packaged
      beef cuts stored at the same temperatures. In containers with the 70% N2 + 30%
      CO2 atmosphere at 20 to 30 kPa and 3 to 4 degrees C, substantial growth of
      Pseudomonas sp. was observed (median of 6 log10 cfu/cm2 at d 21 of storage
      compared with 3 log10 cfu/cm2 for vacuum-packaged beef). Pseudomonas counts were
      lower when the container system was held at 0 to 1 degrees C, especially when
      combined with the pure CO2 atmosphere. As expected for CO2-enriched atmospheres,
      B. thermosphacta was the dominant spoilage bacterium, in the same log10 order as
      the TCC. Lowering the storage temperature and changing the atmosphere to pure CO2
      resulted in a reduction of 1 log10 for TCC (median values after 2 wk of storage).
      Although pathogenic bacteria such as Campylobacter, Salmonella, and Listeria
      monocytogenes were not detected in any sample, further studies are necessary to
      evaluate potential growth risks. The results demonstrate that CO2-enriched and O2
      depleted atmospheres under low pressure have a limited effect on reducing
      bacterial growth, probably because the antibacterial activity of CO2 is
      proportional to the effective concentration of this gas in the headspace. At
      pressures of 20 to 30 kPa, a headspace with pure CO2 would still contain only
      approximately 20 to 30% CO2.

PMID- 16908650
TI  - Modified-atmosphere storage under subatmospheric pressure and beef quality: II.
      Color, drip, cooking loss, sarcomere length, and tenderness.
AB  - Beef has a requirement for refrigerated storage up to 14 d to achieve adequate
      aging and a tender product. To achieve this aging with little spoilage and no
      surface drying, vacuum packaging is attractive, because it is inherently simple
      and offers a clear indication to the packer when the process has failed or there
      is risk of spoilage. However, there is increasing pressure on the meat industry
      to limit the use of packaging materials in view of their cost and the cost
      involved in their recovery and recycling. The purpose of this report was to
      evaluate an alternative storage system in containers using modified atmospheres
      at reduced pressure (approximately 25 kPa). The quality of the meat for both
      container- and vacuum-packed treatments was measured during chilled storage for
      up to 3 wk. Storage time had the most significant effect on quality
      characteristics, irrespective of the packaging method. Storage in containers
      under a 70%N2:30%CO2 gas mixture gave characteristics similar to beef stored
      under vacuum. Storage in containers under 100% CO2 produced less drip loss than
      under 70%N2:30%CO2, but generally container storage produced 3 times as much drip
      loss as vacuum packaging. Shear force of the LM was unaffected by the type of
      packaging, and at d 2 after slaughter (i.e., before the storage trial was begun),
      sarcomere lengths of muscles intended for container storage were similar to those
      destined for vacuum storage. During the packaging treatment, the comparison
      between the storage systems was always done within 1 animal using one carcass
      half for container storage and the other half for vacuum packaging; all bulls
      were shackled from the left hindleg during bleeding. The majority of the muscles
      from the left sides had lower shear force values than those from the right sides
      at the earlier storage times (2 and 9 d after slaughter) but had similar values
      after longer storage (16 and 23 d after slaughter). This is the first report that
      shackling beef carcasses from the left side can result in more tender meat in the
      LM from that side. The increased tenderness in the LM from the shackled side
      probably resulted from an early decrease in pH and an increase in calpain
      activity after mechanical strain of the muscles on the shackled side. This effect
      of shackling should be taken into account when designing systematic comparisons
      of tenderness in beef.

PMID- 16908651
TI  - Terpenes and carbohydrate source influence rumen fermentation, digestibility,
      intake, and preference in sheep.
AB  - We hypothesized that toxins and nutrients in foods interact to influence foraging
      behavior by herbivores. Based on this hypothesis we predicted that 1) terpenes in
      big sagebrush (Artemisia tridentata) influence intake and preference in sheep for
      diets varying in sources of nonstructural (barley grain) and structural (sugar
      beet pulp) carbohydrates, and 2) these effects are due to the differential
      effects of terpenes on fermentation products and apparent digestibility of each
      class of carbohydrates. Lambs were fed 2 isoenergetic and isonitrogenous diets
      with varying proportions of the same ingredients (beet pulp- and barley grain
      based diet) or offered a choice between the 2 diets; all feeds were fed without
      and with terpenes, in consecutive periods. We also compared intake and preference
      of the beet pulp-and barley-based diets before and after the lambs ate a meal of
      sagebrush. Finally, we assessed the effect of terpenes on ruminal variables and
      in vivo digestibility. Lambs ate less when fed beet pulp or when they were
      offered a choice of diets with terpenes (P < 0.001), and intake of the beet pulp
      based diet was the most affected (P < 0.05). Lambs preferred the beet pulp-to the
      grain-based diet with terpenes, but their preference reversed when terpenes were
      removed from the diets (P < 0.05). When lambs were offered both diets, intake and
      preference did not differ (P > 0.20) before eating sagebrush, but they preferred
      the beet pulp-based diet after eating sagebrush (P < 0.05). Intake of sagebrush
      did not differ among groups consuming the test diets (P = 0.21). Addition of
      terpenes to both diets increased the digestibility of DM, NDF, and ADF and
      decreased concentrations of total VFA and acetate (P < 0.05). Terpenes also
      depressed butyrate concentration in the barley-based diet (P < 0.05). Propionate
      concentrations were not affected by terpenes in either feed (P = 0.63). In
      summary, the predominant type of feed ingredient (beet pulp, grain) ingested with
      terpenes influenced fermentation products, intake, and preference in lambs. The
      source of energy from supplements, or other plants in the diet, is likely to
      influence intake and preference for sagebrush in sheep foraging on rangelands.
      Moreover, ingesting terpenes from sagebrush may also influence intake and
      preference for other plant species or supplements.

PMID- 16908652
TI  - Feeding behavior in primiparous lactating sows: impact of a high-fiber diet
      during pregnancy.
AB  - Voluntary feed intake of hyperprolific sows can be insufficient to cover the
      requirements for milk production and maintenance of body condition. A bulky diet
      fed during pregnancy is known to prepare sows for an ad libitum feed supply after
      parturition as shown by the increased feed intake during lactation. The aim of
      this study was to investigate the feeding behavior of young sows during their
      first lactation to evaluate the further impact of the feeding experience acquired
      during pregnancy, through the addition of dietary fiber in the diet. Analysis of
      the feeding pattern and the profile of feed intake tested the hypothesis that
      lactating sows would exhibit different feeding strategies depending on the diet
      during pregnancy. During pregnancy, 24 primiparous sows (Large White x Landrace)
      were offered either 2.4 kg of a control diet/d containing 3.16% crude fiber or
      2.8 kg of a high-fiber diet/d containing 12.42% crude fiber. All sows received 33
      MJ of DE/d. From the first day postpartum until weaning, all sows were offered
      the same lactation diet ad libitum. The feeding pattern during lactation was
      recorded as ADFI, meal frequency, and meal size. In lactation, the ADFI did not
      differ according to the treatment. Compared with control sows, high-fiber sows
      consumed their diet in more (P < 0.05) but smaller meals (P < 0.05). In both
      treatments, ADFI and the number of daily meals increased over weeks of lactation
      (P < 0.001). All sows presented a strong diurnal and bimodal feeding activity
      evolving toward 2 distinct feeding periods occurring from 0500 to 0900 and from
      1400 to 1800 and accounting for 0.64 of the total daily feed intake during the
      third week of lactation. The provision of a fibrous diet during pregnancy pointed
      out the role of an early feeding experience on the development of feeding
      behavior during the first reproductive cycle.

PMID- 16908653
TI  - Effects of dietary humic substances on pig growth performance, carcass
      characteristics, and ammonia emission.
AB  - Five experiments were conducted to test the effects of various dietary humic
      substances (HS; HS1, 2, 3, and 4, each with different fulvic and humic acid
      contents) on pig growth, carcass characteristics, and ammonia emission from
      manure. In Exp. 1, 120 pigs were allotted to 3 dietary treatments without HS
      (control) or with HS1 at 0.5 and 1.0% (8 pens/treatment and 5 pigs/pen) and fed
      diets, based on a 5-phase feeding program, from weaning (d 21.3 +/- 0.3 of age)
      to 60 kg of BW. In Exp. 2 and 3, 384 pigs (192 for each experiment) were allotted
      to 3 dietary treatments without HS, with HS1, or with HS2 (0.5%) for Exp. 2 and
      without HS, or with HS3 or HS4 (0.5%) for Exp. 3 (8 pens/treatment and 8 pigs/pen
      in each experiment). Pigs were fed diets, based on a 6-phase feeding program,
      from weaning (25.4 +/-0.2 and 23.6 +/-0.3 d of age for Exp. 2 and 3,
      respectively) to 110 kg of BW. In Exp. 4, 96 pigs were weaned at 22.1 +/-0.2 d of
      age and allotted to 2 treatments without or with HS1 at 0.5% (6 pens/treatment
      and 8 pigs/pen), and in Exp. 5 96 pigs were weaned at 20.9 +/-0.3 d of age and
      allotted to 3 treatments without HS, or with HS3 or HS4 (0.5%; 4 pens/treatment
      and 8 pigs/pen). Pigs were fed the diets for at least 2 wk before they were moved
      to an environmental chamber to measure aerial ammonia and hydrogen sulfide for 48
      h at 5-min intervals. In Exp. 1, pigs fed diets with HS1 at 0.5% had greater (P <
      0.05) ADG during phase 3 and greater (P < 0.05) G:F during phases 3 and 5 than
      control pigs. In Exp. 2, pigs fed diets with HS1 or HS2 at 0.5% had greater (P <
      0.05) ADG and G:F than control pigs during the entire feeding period, whereas in
      Exp. 3 HS3 or HS4 did not improve pig growth performance. Ammonia emission from
      manure was reduced by 18 or 16% when pigs were fed diets with HS1 (P = 0.067) or
      HS4 (P = 0.054), respectively. The results of this study indicate that the
      effects of dietary HS are variable but may improve growth performance of pigs and
      reduce ammonia emission from manure. Further research is needed to clarify these
      effects and the mechanisms by which HS may cause them.

PMID- 16908654
TI  - Effects of an artificial sweetener on health, performance, and dietary preference
      of feedlot cattle.
AB  - Two experiments examined the effects of a saccharin-based artificial sweetener
      (Sucram) on health, performance, and dietary preference of feedlot cattle. In
      Exp. 1, 200 steer calves (initial BW = 190.4 +/- 1.47 kg) were fed a 65%
      concentrate diet supplemented with or without 200 mg of Sucram/kg (DM basis)
      during a 56-d receiving-growing period. Feeding Sucram did not affect overall (P
      = 0.19) DMI; however, from d 29 to 56, there was a trend (P = 0.10) for increased
      DMI with Sucram (5.71 vs. 6.02 kg/d, respectively). From d 0 to 28 and d 0 to 56,
      there were trends (P = 0.11 and 0.12, respectively) for increased ADG and for
      increased d-56 BW (P = 0.07) for calves fed Sucram. No differences were detected
      (P = 0.82) for receiving (REC) period morbidity. During the finishing (FIN)
      period, 180 steers from the REC period were assigned (9 pens/treatment in a 2 x 2
      factorial design) to the following treatments: 1) control REC/control FIN; 2)
      control REC/Sucram FIN; 3) Sucram REC/control FIN; and 4) Sucram REC/ Sucram FIN.
      Over the FIN period, ADG tended (P = 0.12) to be greater for Sucram; however,
      carcass-adjusted ADG did not differ among treatments. Daily DMI was affected by a
      REC x FIN interaction (P = 0.08), which was the result of greater DMI by cattle
      in the Sucram REC/Sucram FIN treatment and decreased DMI by cattle in the Sucram
      REC/control FIN treatment. In general, changes in carcass characteristics were
      minor. In Exp. 2, 12 steers (initial BW = 395.6 +/- 6.17 kg) were used in a
      simultaneously replicated 3 x 3 Latin square preference test. Each square
      consisted of 3 pens, with 2 steers/pen, and 3 time periods. Bunks had dividers at
      their midpoint, and equal quantities of diet (as-fed basis) were delivered
      randomly on either side of the divider daily. Treatments were: 1) control; 2)
      Sucram = basal diet supplemented with 200 mg of Sucram/kg of DM; and 3) choice =
      control and Sucram on separate sides of the divider. Dietary preference differed
      on d 1 (P = 0.01) and d 3 (P = 0.02) for control vs. choice and Sucram vs.
      choice, with the choice group consuming 0.49 and 1.72 kg of DM more of the Sucram
      diet than the control diet, respectively. This effect, however, was not
      consistent across days, and average DMI did not differ (P = 0.81) among
      treatments. Addition of Sucram to the diet of newly received cattle tended to
      increase receiving period ADG; however, its effects on morbidity, finishing
      performance, and dietary preference were limited.

PMID- 16908655
TI  - Growth response of broilers to spray-dried plasma in pelleted or expanded feed
      processed at high temperature.
AB  - A series of 4 experiments evaluated effects of mash conditioning temperature from
      a pellet mill or expander on performance of broilers fed pelleted diets
      containing spray-dried plasma (SDP). All experiments utilized Ross x Ross 308
      male broilers randomly assigned to their respective treatments (6 or 10
      broilers/pen and 8 or 10 pens/treatment). Treatments in Exp. 1 consisted of a
      control (0% SDP), SDP coated postpelleting, or SDP blended into the meal
      prepelleting. Experiment 2 and 3 included the same 3 treatments as in Exp. 1 but
      with additional treatments of SDP blended into the meal and conditioned at 90 or
      95 degrees C before pelleting. In Exp. 4, treatments consisted of a control (0%
      SDP) or SDP blended into the meal and pelleted (85 degrees C conditioning
      temperature) or expanded (149 degrees C final effective temperature) and then
      pelleted. Corn-soybean meal-based diets were formulated to be equal in lysine and
      ME in all experiments. Pelleted diets were conditioned for 15 s at 85 degrees C,
      and expanded diets were conditioned at 95 degrees C, 29.7 MJ/t, 13.95 kg/cm2 cone
      pressure, exit temperature of 149 degrees C, and then pelleted through a 4 x 32
      mm die. In Exp. 1, ADG and feed intake were improved (P < 0.05) for broilers fed
      SDP from d 1 to 28 of age, with greater BW at d 42. In Exp. 2, both in early (d 1
      to 28 of age) phases, and overall (d 1 to 42 of age), broilers fed SDP had
      improved (P < 0.05) gain and efficiency. In Exp. 3, ADG, feed intake, efficiency
      of gain, and BW were improved (P < 0.01) for broilers fed SDP from d 1 to 21 of
      age, regardless of conditioning temperature. In Exp. 4, broilers fed SDP had
      improved (P < 0.05) gain, BW, and feed intake regardless of processing method.
      Overall, the results of all of the experiments demonstrated that pellet
      conditioning temperature from 85 to 95 degrees C and expander temperatures to 149
      degrees C did not impair the positive growth effects of SDP in pelleted or
      expanded broiler feed.

PMID- 16908656
TI  - Sow shoulder lesions: risk factors and treatment effects on an Ontario farm.
AB  - The objectives of this study were to identify risk factors for the development of
      shoulder lesions in lactating sows and to determine if an effective, economical,
      and practical treatment could be designed. The study was conducted at a 300-sow
      farrow-to-finish swine farm in Ontario between July and December 2004. Sow data
      were recorded on either the day of or 1 d after entering the farrowing crate and
      before farrowing had occurred. The right and left shoulders of the sows were
      assigned a score between 0 (normal) and 4 (lesion > 2.3 cm in diam.) on d 1 of
      the study and weekly thereafter throughout lactation. If a lesion developed, sows
      were randomly placed into 1 of 3 treatment groups. Groups consisted of a control
      group that received no treatment, a group that had a 0.2-cm thick, 60 x 60-cm,
      stainless steel plate attached to the bottom of the farrowing crate, and a group
      that had a 3.8-cm thick, 60 x 60-cm rubber mat attached to the bottom of the
      farrowing crate. Of the 310 sows involved in the study, 107 (34%) developed a
      lesion with a score of 3 or 4. Multivariate regression analysis identified body
      condition at weaning, flank-to-flank measurements at weaning, breed, parity,
      farrowing room section, and weaning weight of the litter as significantly
      associated with development of a shoulder lesion of score 3 or 4. The average
      number of days for the lesions to be completely resolved was 25 for sows
      receiving rubber mats, 32 for the controls, and 39 for the sows receiving
      stainless steel plates. Rubber mats attached to the bottom of the farrowing
      crates decreased the time required to heal the lesions when compared with
      controls. The low cost per mat (less than 0.90 dollars factoring in repeated use)
      makes it an economical and effective treatment.

PMID- 16908657
TI  - Influence of genotype and diet on steer performance, manure odor, and carriage of
      pathogenic and other fecal bacteria. I. Animal performance.
AB  - Although Brahman crosses constitute a large portion of US beef cattle, little
      information is available on their response to diverse feed resources compared
      with Bos taurus steers. Thus, the objectives were to evaluate genotype and diet
      effects on steer performance during the growing period and subsequent response to
      a high grain diet during the finishing period. Fifty-one steers [0 (15), 1/4
      (20), 1/2 (7), and 3/4 Brahman (9), with the remaining proportion being MARC III]
      were allotted to 8 pens. Beginning on December 2, steers were individually fed
      chopped bromegrass hay (n = 26; DM = 85%, CP = 9.5%, ME = 2.19 Mcal/kg) or a corn
      silage-based diet (n = 25; DM = 51%, CP = 11.9%, ME = 2.75 Mcal/kg) for 119 d.
      All steers were then fed a high corn diet (DM = 79%, CP = 11.7%, ME = 3.08
      Mcal/kg) to a target BW of 560 kg (176 d). Data were analyzed by ANOVA, with
      genotype, growing diet, and the 2-way interaction included. The interaction was
      not significant (P > 0.25). The MARC III and 1/2 Brahman steers weighed more (P <
      0.01) than 1/4 or 3/4 Brahman steers initially and at the end of the growing
      period. Weight of bromegrass-fed (325 kg) steers was less than that of corn
      silage-fed (384 kg) steers at the end of the growing period. Steer ADG and intake
      of DM, CP, and ME were less (P = 0.087 to 0.001) for 1/4 and 3/4 Brahman than for
      0 or 1/2 Brahman steers during growing, finishing, and total, but efficiency of
      gain did not differ (P > 0.10). Carcass weight, marbling score, quality grade (P
      < 0.05), and kidney fat (P = 0.06) differed among genotypes. Daily DMI (6.91 vs.
      7.06 kg) was similar, but CP (0.66 vs. 0.84 kg) and ME (15.2 vs. 19.4 Mcal)
      intake of bromegrass fed was less (P = 0.001) than those of corn silage-fed
      steers. Values for DMI/gain (22.3 vs. 7.43 kg/kg), CP intake/gain (2.13 vs. 0.88
      kg/kg), and ME intake/gain (48.8 vs. 20.4 Mcal/kg) were greater (P < 0.001) in
      bromegrass-fed than corn silage-fed steers. Over the total study, ADG was lower
      (0.96 vs. 1.01 kg), and DMI (7.82 vs. 7.19 kg), DMI/gain (8.21 vs. 7.10 kg/kg),
      and ME intake/gain (22.6 vs. 20.9 Mcal/kg) were greater (P < 0.05) in bromegrass
      fed than in corn silage-fed steers. Carcass weight, dressing percent, adjusted
      backfat, and yield grade (P < 0.05) were greater for corn silage-fed than for
      bromegrass-fed steers. Feed intake and performance, but not efficiency, differed
      among these genotypes. Compensatory performance during finishing was insufficient
      to overcome reduced performance during the growing period.

PMID- 16908658
TI  - Influence of genotype and diet on steer performance, manure odor, and carriage of
      pathogenic and other fecal bacteria. II. Pathogenic and other fecal bacteria.
AB  - This study assessed the influence of cattle genotype and diet on the carriage and
      shedding of zoonotic bacterial pathogens and levels of generic Escherichia coli
      in feces and ruminal contents of beef cattle during the growing and finishing
      periods. Fifty-one steers of varying proportions of Brahman and MARC III [0 (15),
      1/4 (20), 1/2 (7), and 3/4 Brahman (9)] genotypes were divided among 8 pens, such
      that each breed type was represented in each pen. Four pens each were assigned to
      1 of 2 diets [100% chopped bromegrass hay or a diet composed primarily of corn
      silage (87%)] that were individually fed for a 119-d growing period, at which
      time the steers were switched to the same high-concentrate, corn-based finishing
      diet and fed to a target weight of 560 kg. Feces or ruminal fluid were collected
      and analyzed at alternating intervals of 14 d or less. Generic E. coli
      concentrations in feces or ruminal fluid did not differ (P > 0.10) by genotype or
      by growing diet in the growing or finishing periods. However, the concentrations
      in both feces and ruminal fluid increased in all cattle when switched to the same
      high-corn diet in the finishing period. There was no effect (P > 0.25) of diet or
      genotype during either period on E. coli O157 shedding in feces. Forty-one
      percent of the steers were positive for Campylobacter spp. at least once during
      the study, and repeated isolations of Campylobacter spp. from the same steer were
      common. These repeated isolations from the same animals may be responsible for
      the apparent diet (P = 0.05) and genotype effects (P = 0.02) on Campylobacter in
      feces in the finishing period. Cells bearing stx genes were detected frequently
      in both feces (22.5%) and ruminal fluid (19.6%). The number of stx-positive fecal
      samples was greater (P < 0.05) for 1/2 Brahman steers (42.9%) than for 1/4
      Brahman (25.0%) or 3/4 Brahman steers (22.2%), but were not different compared
      with MARC III steers (38.3%). The greater feed consumption of 1/2 Brahman and
      MARC III steers may have resulted in greater starch passage into the colon,
      accompanied by an increase in fecal bacterial populations, which may have further
      improved the ability to detect stx genes in these cattle. There was no
      correlation between either ADG or daily DMI and the number of positive samples of
      E. coli O157, Campylobacter spp., or stx genes, which agrees with our current
      understanding that these microorganisms occur commonly in, and with no measurable
      detriment to, healthy cattle.

PMID- 16908659
TI  - Influence of genotype and diet on steer performance, manure odor, and carriage of
      pathogenic and other fecal bacteria. III. Odorous compound production.
AB  - Three beef cattle diets were assessed for their potential to produce odorous
      compounds from cattle feces excreted during the growing and finishing periods.
      Eight pens containing 51 steers of varying proportions of Brahman and MARC III
      genotypes were fed either a chopped bromegrass hay diet or a corn silage diet for
      a 119-d growing period. After the growing period, all steers were switched to the
      same high-corn finishing diet (high corn) and fed to a target weight of 560 kg
      (finishing period). Fecal slurries were prepared from a composite of fresh fecal
      pats collected in each pen during both periods and incubated anaerobically. In
      additional flasks, starch, protein, or cellulose was added to the composite fecal
      subsamples to determine the preferred substrates for fermentation and odorous
      compound production. The content and composition of the fermentation products
      varied both initially and during the incubation, depending on the diet fed to the
      steers. The corn silage and high corn feces had the greater initial content of
      VFA (381.0 and 524.4 micromol/g of DM, respectively) compared with the bromegrass
      feces (139.3 micromol/g of DM) and accumulated more VFA than the bromegrass feces
      during the incubation. l-Lactic acid and VFA accumulation in the high corn and
      corn silage feces was at the expense of starch, based on starch loss and the
      production of straight-chain VFA. In the bromegrass feces, accumulation of
      branched-chain VFA and aromatic compounds and the low starch availability
      indicated that the protein in the feces was the primary source for odorous
      compound production. Substrate additions confirmed these conclusions. We conclude
      that starch availability was the primary factor determining accumulation and
      composition of malodorous fermentation products, and when starch was unavailable,
      fecal microorganisms utilized protein.

PMID- 16908660
TI  - Effects of condensed tannins supplementation level on weight gain and in vitro
      and in vivo bloat precursors in steers grazing winter wheat.
AB  - Research was conducted to determine the effects of level of supplementation with
      quebracho condensed tannins (CT) on in vitro ruminal fluid gas production, in
      vivo ruminal fluid protein fractions, bloat dynamics, and ADG of steers grazing
      winter wheat. Two experiments were conducted to 1) enumerate the effect of
      ruminal fluid from steers fed quebracho CT (0, 1, and 2% CT/kg of DMI) on in
      vitro gas and methane production from minced fresh wheat forage; and 2) quantify
      the influence of CT supplementation on ruminal protein characteristics, biofilm
      complexes, bloat potential, and ADG of steers grazing wheat pasture. Eighteen
      ruminally cannulated steers (386 +/- 36 kg of BW) were randomly allocated to 1 of
      3 treatments that included a control (water infusion) and 2 CT treatment levels
      (1 or 2% CT/kg of DMI). Treatments were administered daily (63 d) through the
      rumen cannula as pre-mixes with warm water (approximately 30 degrees C). Rumen
      contents were collected 2 h postinfusion (at 1030 to 1130) on d 0, 20, 40, 50,
      and 60. Bloat was visually scored daily for 5 d each wk. In Exp. 1,
      supplementation of CT decreased the rate of in vitro gas production in a dose
      dependent response. In Exp. 2, ADG increased (P < 0.04) at both levels of CT
      supplementation. Mean bloat score across stage of growth and replicates decreased
      linearly with increasing CT supplementation; bloat scores were greater (P <
      0.001) for the vegetative than for the reproductive stage of plant growth.
      Biofilm production and rumen fluid protein fractions varied among CT treatments
      and stage of growth. Addition of CT reduced the severity of bloat, principally
      through reducing microbial activities, biofilm production, and ruminal gas
      production. Quebracho CT is potentially a value-added supplement that can
      decrease the impacts of frothy bloat and increase BW gains in stocker cattle
      wheat systems.

PMID- 16908661
TI  - Impact of biological and economic variables on optimal parity for replacement in
      swine breed-to-wean herds.
AB  - Voluntary and involuntary culling practices determine the average parity when
      sows are replaced in a herd. Underlying these practices is the economic effect of
      replacing a sow at different parities. A dynamic programming model was used to
      find the optimal parity and net present value in breed-to-wean swine herds. The
      model included income and costs per parity weighted by the discount rate and sow
      removal rate. Three scenarios that reflect a wide range of cases were considered:
      low removal rates per parity with no salvage value (LRNS), high removal rates per
      parity with no salvage value (HRNS), and high removal rates per parity with a
      percentage of the sows having a salvage value (HRYS). The optimal parity of
      replacement for the base biological and economic conditions was 4 and 5 parities
      in the high and low removal scenarios, respectively. Sensitivity analyses
      identified the variables influencing the optimal replacement parity. Optimal
      parity of replacement ranged from 3 to 7 parities in the low replacement
      scenario, compared with 1 to 5 parities in the high replacement scenarios. Sow
      replacement cost and salvage value had the greatest impact on optimal parity of
      replacement followed by revenues per piglet weaned. The discount rate and number
      of parities per year generally had little influence on optimal parity. For
      situations with high sow costs, low salvage values, and low revenues per piglet,
      the optimal parity at removal was as high as 6 to 10 parities, and for situations
      with low sow cost, high salvage values, and high revenues per piglet, the optimal
      parity at removal was as low as 1 to 2 parities depending on removal rates. The
      modified internal rate of return suggested that, for most LRNS and HRYS scenarios
      considered, investment in a swine breed-to-wean enterprise was favored over other
      investments involving a similar risk profile. Our results indicate that in US
      breeding herds, sows are culled on average near the optimal parity of 4. However,
      the optimization process should be a dynamic one that adapts to changes in
      replacement rates, salvage value, replacement cost, and revenues per piglet.

PMID- 16908662
TI  - Fiber production and properties in genetically furred and furless rabbits.
AB  - The objectives of this study were to describe and compare means and measures of
      variability of fiber characteristics and fiber production between genetically
      furred and furless rabbits and among classes of furless rabbits. An F1 generation
      of rabbits was produced by mating New Zealand White does to a rare, furless Mini
      Lop buck. All F1 offspring had normal coats of fur. Inter se random matings of
      the F1 stock (barring full-sibling matings) were made to produce the F2
      generation that consisted of approximately 75% furred and 25% furless progeny.
      Furless animals were further subjectively classified into 3 distinct classes (1
      to 3) having increasingly more fur. In yr 1, 17 furred and 20 furless rabbits
      (age 28 to 49 d) were randomly assigned to growing pens, and in yr 2, 17
      additional furless and 9 additional furred rabbits were included to increase the
      size. After 6 wk, the rabbits were weighed, and a measured area of fur
      (approximately 20 cm2) was shorn from the left flank of each rabbit. This fiber
      was weighed and measured for staple length, fiber diameter, prickle factor (% of
      fibers > 30 microm in diameter), and fiber curvature. Fiber production per unit
      area of skin was calculated and fiber production per animal was estimated. In yr
      2, all of the furless and 2 of the furred rabbits were shorn over their entire
      bodies to obtain direct measurements of total fur weight. Furless rabbits were 9%
      heavier (1,941 vs. 1,783 g of BW, P < 0.01) and produced approximately 90% less
      fiber per unit area of skin than furred rabbits (1.74 vs. 15.83 mg/cm2, P <
      0.01). The fibers from furless rabbits were shorter (1.54 vs. 2.56 cm, P < 0.01)
      and coarser (15.8 vs. 14.5 microm diameter, P < 0.01) than those from furred
      rabbits and exhibited greater prickle factor (11.3 vs. 3.5%, P < 0.01) and
      curvature values (47.5 vs. 38.5 deg/mm, P < 0.01). Class 3 furless rabbits were
      heavier than rabbits of classes 1 and 2 (2,075 vs. 1,817 and 1,981 g of BW,
      respectively, P < 0.05). Means for actual total fiber production per animal for
      classes 1 to 3 were 0.64, 2.07, and 8.68 g, respectively, compared with 23.0 g
      for furred rabbits (P < 0.01). Although some similarities were present, several
      of the correlations involving fiber properties and BW were substantially
      different (e.g., BW vs. staple length and fiber diameter vs. weight of fiber per
      unit area) for furred and furless groups. These results, and those reported
      elsewhere from a series of experiments, support the potential for production of
      furless rabbits in arid and tropical environments.

PMID- 16908663
TI  - Comparison of visual and electronic identification devices in pigs: on-farm
      performances.
AB  - A total of 1,822 pigs from 2 farms (farm A, n = 1,032; farm B, n = 790) were used
      to evaluate pig traceability under on-farm conditions by using identification
      devices (n = 4,434) of different technologies. The devices were visual ear tags
      (n = 1,533; Model 1, n = 776; Model 2, n = 757), electronic ear tags (n = 1,446;
      half-duplex, n = 702; full-duplex, n = 744), and intraperitoneally injected
      transponders (n = 1,455; half-duplex, n = 732; full-duplex, n = 723). A group of
      790 pigs wore 3 types of devices, and 1,032 wore 2 devices. Piglets were
      identified before (wk 1 to 3 of age; farm A) or after (wk 3 to 4 of age; farm B)
      weaning and intensively fattened until approximately 100 kg of BW. Readability of
      devices was checked at each farm operation by using standardized handheld
      transceivers. No negative effects of the identification devices on animal health
      (mortality rate, 8.4%) or performance were detected. On-farm losses averaged 1.6%
      for ear tags (visual, 0.8%; half-duplex, 1.9%; full-duplex, 2.7%; P > 0.05) and
      1.8% for intraperitoneally injected transponders (half-duplex, 1.7%; full-duplex,
      1.9%; P > 0.05). Moreover, 1.4% electronic failures occurred in the electronic
      ear tags (half-duplex, 2.2%; full-duplex, 0.6%; P < 0.05) but not in the
      intraperitoneally injected transponders. Final on-farm readability was greater (P
      < 0.05) for visual ear tags (99.2%) than for electronic ear tags (half-duplex,
      95.9%; full-duplex, 96.7%; P > 0.05). Readability for intraperitoneally injected
      transponders was intermediate (half-duplex, 98.3%; full-duplex, 98.1%; P > 0.05).
      Electronic devices were in all cases easier and faster to read than the visual
      ear tags. Visual ear tags and intraperitoneally injected transponders were
      efficiently retained under conditions of commercial pig farms, which agrees with
      the minimum values recommended by the International Committee for Animal
      Recording (> 98%). When readability and reading ease were also included as
      decision criteria, injectable transponders were preferred.

PMID- 16908664
TI  - Effects of pre- and postpartum nutrition on reproduction in spring calving cows
      and calf feedlot performance.
AB  - Crossbred, spring-calving cows (yr 1, n = 136; yr 2, n = 113; yr 3, n = 113) were
      used in a 3-yr experiment to evaluate the influence of supplemental protein
      prepartum and grazing subirrigated meadow postpartum on pregnancy rates and calf
      feedlot performance. A 2 x 2 factorial arrangement of treatments was used in a
      switchback design. From December 1 to February 28, cows grazed dormant upland
      range in 8 pastures (32 +/- 2 ha each). The equivalent of 0.45 kg of
      supplement/cow per d (42% CP) was provided to half of the cows on a pasture basis
      3 d/wk. For 30 d before the beginning of breeding (May 1 to May 31), half of the
      cows grazed a common subirrigated meadow (58 ha), and the remainder was fed grass
      hay in a drylot. Cow BW and BCS were monitored throughout the year, and steer
      calf performance was determined until slaughter. Feeding supplement prepartum
      improved (P = 0.01 to P < 0.001) BCS precalving (5.1 vs. 4.7) and prebreeding
      (5.1 vs. 4.9) and increased (P = 0.02) the percentage of live calves at weaning
      (98.5 vs. 93.6%) but did not affect (P = 0.46) pregnancy rate (93 vs. 90%).
      Calves born to dams fed supplement prepartum had similar (P = 0.29) birth weight
      (37 vs. 36 kg) but greater (P = 0.02) weaning weight (218 vs. 211 kg). However,
      steer feedlot DMI (8.53 vs. 8.48 kg), ADG (1.6 vs. 1.6 kg), and carcass weight
      (369 vs. 363 kg) were not affected (P = 0.23 to P = 0.89) by prepartum
      supplementation. Allowing cows to graze subirrigated meadow postpartum improved
      (P < 0.001) BCS prebreeding (5.2 vs. 4.9) but did not affect (P = 0.88) pregnancy
      rate (92 vs. 91%). Allowing cows to graze subirrigated meadow increased (P =
      0.01) calf weaning weight (218 vs. 211 kg) but not (P = 0.62 to P = 0.91) feedlot
      DMI (8.4 vs. 8.3 kg), ADG (1.6 vs. 1.6 kg), or carcass weight (363 vs. 362 kg) of
      their steer calves. Increased percentage of live calves at weaning as a result of
      feeding supplemental protein increased net returns at weaning and after finishing
      in the feedlot. Net returns were increased by allowing cows to graze subirrigated
      meadow postpartum regardless of whether calves were marketed at weaning or after
      finishing in the feedlot.

PMID- 16908665
TI  - National Pork Producers Council Maternal Line National Genetic Evaluation
      Program: a comparison of sow longevity and trait associations with sow longevity.
AB  - Data from the National Pork Producers Council Maternal Line National Genetic
      Evaluation Program were used to compare longevity of sows from 6 commercial
      genetic lines and to estimate the phenotypic associations of sow longevity with
      gilt backfat thickness, ADG, age at first farrowing, litter size at first
      farrowing, litter weight at first farrowing, average feed intake during
      lactation, and average backfat loss during lactation. The lines evaluated were
      American Diamond Genetics, Danbred North America, Dekalb-Monsanto DK44, Dekalb
      Monsanto GPK347, Newsham Hybrids, and National Swine Registry. The data set
      contained information from 3,251 gilts, of which 17% had censored longevity
      records (sows lived longer than 6 parities). The line comparison was carried out
      by analyzing all lines simultaneously. Because the survival distribution
      functions differed among genetic lines, later analyses were carried out
      separately for each genetic line. All analyses were based on the non-parametric
      proportional hazard (Cox model). Dekalb-Monsanto GPK347 sows had a lower risk of
      being culled than sows from the other lines. Moreover, the shape of the survival
      distribution function of the Delkab-Monsanto GPK347 line was different from the
      other 5 lines. The Dekalb-Monsanto 347 line had lower culling rates because they
      had lower gilt reproductive failure before the first parity than gilts from the
      other lines. Within line, sows with lower feed intake and greater backfat loss
      during lactation had a shorter productive lifetime. Thus, producers should
      implement management practices having positive effects on sow lactation feed
      intake. Additionally, the swine genetics industry is challenged to simultaneously
      improve efficiency of gain of their terminal market pigs and to obtain high feed
      intake during lactation of their maternal lines for future improvement of sow
      longevity. Recording sow feed intake and backfat loss during lactation in nucleus
      and multiplication breeding herds should be considered. Between-line differences
      in this study indicate that it is possible to select for sow longevity, but more
      research is needed to determine the most efficient selection methods to improve
      sow longevity.

PMID- 16908666
TI  - From imaging to understanding: Frontiers in Live Cell Imaging, Bethesda, MD,
      April 19-21, 2006.
AB  - A recent meeting entitled Frontiers in Live Cell Imaging was attended by more
      than 400 cell biologists, physicists, chemists, mathematicians, and engineers.
      Unlike typical special topics meetings, which bring together investigators in a
      defined field primarily to review recent progress, the purpose of this meeting
      was to promote cross-disciplinary interactions by introducing emerging methods on
      the one hand and important biological applications on the other. The goal was to
      turn live cell imaging from a "technique" used in cell biology into a new
      exploratory science that combines a number of research fields.

PMID- 16908667
TI  - Phosphoinositide signaling plays a key role in cytokinesis.
AB  - To perform the vital functions of motility and division, cells must undergo
      dramatic shifts in cell polarity. Recent evidence suggests that polarized
      distributions of phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol
      3,4,5-trisphosphate, which are clearly important for regulating cell morphology
      during migration, also play an important role during the final event in cell
      division, which is cytokinesis. Thus, there is a critical interplay between the
      membrane phosphoinositides and the cytoskeletal cortex that regulates the complex
      series of cell shape changes that accompany these two processes.

PMID- 16908668
TI  - Perturbing integrin function inhibits microtubule growth from centrosomes,
      spindle assembly, and cytokinesis.
AB  - In many mammalian cell types, integrin-mediated cell-matrix adhesion is required
      for the G1-S transition of the cell cycle. As cells approach mitosis, a dramatic
      remodeling of their cytoskeleton accompanies dynamic changes in matrix adhesion,
      suggesting a mechanistic link. However, the role of integrins in cell division
      remains mostly unexplored. Using two cellular systems, we demonstrate that a
      point mutation in the beta1 cytoplasmic domain (beta1 tail) known to decrease
      integrin activity supports entry into mitosis but inhibits the assembly of a
      radial microtubule array focused at the centrosome during interphase, the
      formation of a bipolar spindle at mitosis and cytokinesis. These events are
      restored by externally activating the mutant integrin with specific antibodies.
      This is the first demonstration that the integrin beta1 tail can regulate
      centrosome function, the assembly of the mitotic spindle, and cytokinesis.

PMID- 16908669
TI  - Functional implications of calcium permeability of the channel formed by pannexin
      1.
AB  - Although human pannexins (PanX) are homologous to gap junction molecules, their
      physiological function in vertebrates remains poorly understood. Our results
      demonstrate that overexpression of PanX1 results in the formation of Ca(2+)
      permeable gap junction channels between adjacent cells, thus, allowing direct
      intercellular Ca(2+) diffusion and facilitating intercellular Ca(2+) wave
      propagation. More intriguingly, our results strongly suggest that PanX1 may also
      form Ca(2+)-permeable channels in the endoplasmic reticulum (ER). These channels
      contribute to the ER Ca(2+) leak and thereby affect the ER Ca(2+) load. Because
      leakage remains the most enigmatic of those processes involved in intracellular
      calcium homeostasis, and the molecular nature of the leak channels is as yet
      unknown, the results of this work provide new insight into calcium signaling
      mechanisms. These results imply that for vertebrates, a new protein family,
      referred to as pannexins, may not simply duplicate the connexin function but may
      also provide additional pathways for intra- and intercellular calcium signaling
      and homeostasis.

PMID- 16908670
TI  - ATP-binding cassette transporter A7 enhances phagocytosis of apoptotic cells and
      associated ERK signaling in macrophages.
AB  - The mammalian ATP-binding cassette transporters A1 and A7 (ABCA1 and -A7) show
      sequence similarity to CED-7, a Caenorhabditis elegans gene that mediates the
      clearance of apoptotic cells. Using RNA interference or gene targeting, we show
      that knock down of macrophage ABCA7 but not -A1 results in defective engulfment
      of apoptotic cells. In response to apoptotic cells, ABCA7 moves to the macrophage
      cell surface and colocalizes with the low-density lipoprotein receptor-related
      protein 1 (LRP1) in phagocytic cups. The cell surface localization of ABCA7 and
      LRP1 is defective in ABCA7-deficient cells. C1q is an opsonin of apoptotic cells
      that acts via phagocyte LRP1 to induce extracellular signal-regulated kinase
      (ERK) signaling. We show that ERK signaling is required for phagocytosis of
      apoptotic cells and that ERK phosphorylation in response to apoptotic cells or
      C1q is defective in ABCA7-deficient cells. These studies reveal a major role of
      ABCA7 and not -A1 in the clearance of apoptotic cells and therefore suggest that
      ABCA7 is an authentic orthologue of CED-7.

PMID- 16908671
TI  - Plectin-controlled keratin cytoarchitecture affects MAP kinases involved in
      cellular stress response and migration.
AB  - Plectin is a major intermediate filament (IF)-based cytolinker protein that
      stabilizes cells and tissues mechanically, regulates actin filament dynamics, and
      serves as a scaffolding platform for signaling molecules. In this study, we show
      that plectin deficiency is a cause of aberrant keratin cytoskeleton organization
      caused by a lack of orthogonal IF cross-linking. Keratin networks in plectin
      deficient cells were more susceptible to osmotic shock-induced retraction from
      peripheral areas, and their okadaic acid-induced disruption (paralleled by stress
      activated MAP kinase p38 activation) proceeded faster. Basal activities of the
      MAP kinase Erk1/2 and of the membrane-associated upstream protein kinases c-Src
      and PKCdelta were significantly elevated, and increased migration rates, as
      assessed by in vitro wound-closure assays and time-lapse microscopy, were
      observed. Forced expression of RACK1, which is the plectin-binding receptor
      protein for activated PKCdelta, in wild-type keratinocytes elevated their
      migration potential close to that of plectin-null cells. These data establish a
      link between cytolinker-controlled cytoarchitecture/scaffolding functions of
      keratin IFs and specific MAP kinase cascades mediating distinct cellular
      responses.

PMID- 16908672
TI  - N-syndecan deficiency impairs neural migration in brain.
AB  - N-syndecan (syndecan-3) is a transmembrane proteoglycan that is abundantly
      expressed in the major axonal pathways and in the migratory routes of the
      developing brain. When ligated by heparin-binding (HB) growth-associated molecule
      (GAM; pleiotrophin), N-syndecan mediates cortactin-Src kinase-dependent neurite
      outgrowth. However, the functional role of N-syndecan in brain development
      remains unexplored. In this study, we show that N-syndecan deficiency perturbs
      the laminar structure of the cerebral cortex as a result of impaired radial
      migration. In addition, neural migration in the rostral migratory stream is
      impaired in the N-syndecan-null mice. We suggest that the migration defect
      depends on impaired HB-GAM-induced Src kinase activation and haptotactic
      migration. Furthermore, we show that N-syndecan interacts with EGF receptor
      (EGFR) at the plasma membrane and is required in EGFR-induced neuronal migration.

PMID- 16908673
TI  - Hemodynamic investigation of the left renal vein in pediatric varicocele: Doppler
      US, venography, and pressure measurements.
AB  - PURPOSE: To evaluate prospectively the hemodynamic state of the left renal vein
      with Doppler ultrasonography (US) and venography in pediatric patients with
      varicocele to assess the "nutcracker phenomenon." MATERIALS AND METHODS: The
      institutional review board considered this study ethically sound, and parental
      informed consent was obtained for all subjects. Doppler US of the left renal vein
      was performed in 27 consecutive boys with varicocele (age range, 7-15 years;
      mean, 11.9 years) and in 20 boys without varicocele as control subjects (age
      range, 7-17 years; mean, 11.4 years). Doppler US was used to evaluate left renal
      vein diameters and peak velocities in the proximal left renal vein near the renal
      hilum and in the left renal vein between the aorta and superior mesenteric artery
      (aortomesenteric portion). The diameter ratios and peak velocity ratios between
      two sites were obtained. For statistical comparison of results, the t test was
      used. Left renal venography and renocaval pressure measurement were performed in
      13 patients with varicocele. The Fisher exact test was used to evaluate the
      associations between the nutcracker phenomenon (renocaval pressure gradient >/=3
      mm Hg) and the development of collateral veins. RESULTS: The diameters of the
      proximal left renal vein and the peak velocities in the aortomesenteric portion
      of the left renal vein were significantly different between the varicocele group
      and the control group (P < .001). The diameter ratios (5.7 +/- 1.8 [standard
      deviation]) and peak velocity ratios (5.2 +/- 2.6) in patients with varicocele
      were significantly higher than those in control subjects (3.5 +/- 1.0 and 3.1 +/-
      0.8, respectively) (P < .005). According to findings at left renal venography (n
      = 13), 10 patients (77%) met the criteria for the nutcracker phenomenon. The
      nutcracker phenomenon was significantly associated with the development of
      collateral veins (P = .035). CONCLUSION: Doppler US and venography of the left
      renal vein can show hemodynamic changes of the left renal vein and depict the
      presence of the nutcracker phenomenon in pediatric varicocele.

PMID- 16908674
TI  - Detection of colorectal polyps: comparison of multi-detector row CT and MR
      colonography in a colon phantom.
AB  - PURPOSE: To compare multi-detector row (four- and 16-section) computed tomography
      (CT), including a low-dose protocol, with high-field-strength (1.5- and 3.0-T)
      magnetic resonance (MR) imaging for reader detection of colorectal polyps in a
      colon phantom. MATERIALS AND METHODS: A colon phantom with simulated haustral
      folds and 10 polyps of varying size (2.0-8.0 mm) was imaged at four- and 16
      section CT (section thicknesses of 1.25 and 0.75 mm, reconstruction increments of
      0.8 and 0.7 mm, and 100 and 10 mAs, respectively, and 120 kV for both) and at 1.5
      and 3.0-T MR imaging (three-dimensional gradient-recalled echo sequence, section
      thickness of 1.4 mm). Three-dimensional endoluminal images were assessed by 10
      reviewers for each modality regarding polyp detection. Comparisons of
      sensitivities were performed by using logistic regression. RESULTS: Overall,
      polyps were detected with a sensitivity of 87% (95% confidence interval [CI]:
      80%, 94%) at four-section CT, 92% (95% CI: 87%, 97%) at 16-section CT, 56% (95%
      CI: 46%, 66%) at 1.5-T MR imaging, and 55% (95% CI: 45%, 65%) at 3.0-T MR
      imaging. The detection of polyps at least 4 mm in diameter was not influenced by
      the modality or radiation dose (sensitivity of 100%). CT performed in low-dose
      mode depicted all polyps with a diameter of at least 3 mm. Polyps smaller than 3
      mm in diameter were detected with a sensitivity of 7.5% (1.5-T MR imaging), 22.5%
      (3.0-T MR imaging), and 20% (low-dose CT); detection rates were significantly
      greater (P < .001) with normal-dose CT (four section, 67.5%; 16 section, 82.5%).
      Increased spatial resolution (with CT) and higher field strength (with MR
      imaging) had no significant effect on polyp detection. CONCLUSION: With both
      multi-detector row CT and MR imaging, readers detected polyps above the
      clinically relevant threshold diameter of 6 mm, with similar sensitivities.

PMID- 16908675
TI  - Transjugular intrahepatic portosystemic shunt patency and clinical outcome in
      patients with Budd-Chiari syndrome: covered versus uncovered stents.
AB  - PURPOSE: To retrospectively compare primary patency and reintervention rates,
      clinical outcome, and improvement in hepatic dysfunction (Child-Pugh score) in
      patients with Budd-Chiari syndrome treated with transjugular intrahepatic
      portosystemic shunt (TIPS) using bare stents or expanded polytetrafluoroethylene
      (PTFE)-covered stents. MATERIALS AND METHODS: Approval of study and treatment
      protocol and waiver of informed consent for the retrospective study were obtained
      from institutional review board. Informed consent was obtained from each patient
      before procedure. Four male and nine female consecutive patients (mean age, 35.7
      years) with Budd-Chiari syndrome treated with TIPS from January 1994 to November
      2003 were included. In six patients, TIPS creation was performed with bare stents
      (group A). After April 2001, TIPS creation was performed in seven patients with
      expanded PTFE-covered stent-grafts (group B). Follow-up (group A mean, 22.7
      months +/- 10.53 [standard deviation]; group B mean, 23.1 months +/- 7.81) was
      performed at 7 days, 30 days, and 3 months and subsequently every 3 months. Liver
      function was evaluated every 3 months. Primary end points were 6- and 12-month
      TIPS patency rates. Secondary end points were reintervention rate and clinical
      outcome. Patency rates were estimated (Kaplan-Meier method) and compared (log
      rank test). Continuous (Mann-Whitney U test) and categoric (chi(2) test) data
      were compared. Significant differences before and after treatment were determined
      (Wilcoxon test). RESULTS: Mean primary patency duration was 4.46 months +/- 3.40
      in group A and 22.29 months +/- 8.15 in group B. In group B, a significant
      increase in primary patency rate (100% and 85.7% vs 16.7% and 0% at 6 and 12
      months; P < .001, log-rank test) and a decrease in reintervention rate (0.29 +/-
      0.49 vs 6.17 +/- 1.72, P < .001) were observed. Both groups had a significantly
      decreased Child-Pugh score; group B had a more persistent and significantly
      higher reduction. CONCLUSION: Expanded PTFE-covered stent-grafts significantly
      increased primary patency rate of TIPS in patients with Budd-Chiari syndrome,
      with reduced reintervention rate and prolonged clinical improvement.

PMID- 16908676
TI  - Sensorimotor cortex localization: comparison of magnetoencephalography,
      functional MR imaging, and intraoperative cortical mapping.
AB  - PURPOSE: To prospectively evaluate magnetoencephalography (MEG) and functional
      magnetic resonance (MR) imaging, as compared with intraoperative cortical
      mapping, for identification of the central sulcus. MATERIALS AND METHODS: Fifteen
      patients (six men, nine women; age range, 25-58 years) with a lesion near the
      primary sensorimotor cortex (13 gliomas, one cavernous hemangioma, and one
      meningioma) were examined after institutional review board approval and written
      informed consent from each patient were obtained. At MEG, evoked magnetic fields
      to median nerve stimulation were recorded; at functional MR imaging, hemodynamic
      responses to self-paced palmar flexion of the wrist were imaged. General linear
      model analysis with contextual clustering (P < .01) was used to analyze
      functional MR imaging data, and dipole modeling was used to analyze MEG data. MEG
      and functional MR localizations were compared with intraoperative cortical
      mappings. The distance from the area of functional MR imaging activation to the
      tumor margin was compared between the patients with discordant and those with
      concordant intraoperative mapping findings by using unpaired t testing. RESULTS:
      MEG depicted the central sulcus correctly in all 15 patients, as verified at
      intraoperative mapping. The functional MR imaging localization results agreed
      with the intraoperative mappings in 11 patients. In all four patients with a
      false localization, the primary activation was in the postcentral sulcus region,
      but it did not differ significantly from the primary activation in the patients
      with correct localization with respect to proximity to the tumor (P = .38).
      Furthermore, at functional MR imaging, multiple nonprimary areas were activated,
      with considerable interindividual variation. CONCLUSION: Although both MEG and
      functional MR imaging can provide useful information for neurosurgical planning,
      in the present study, MEG proved to be superior for locating the central sulcus.
      Activation of multiple nonprimary cerebral areas may confound the interpretation
      of functional MR imaging results.

PMID- 16908677
TI  - Pulmonary nodules detected at lung cancer screening: interobserver variability of
      semiautomated volume measurements.
AB  - PURPOSE: To retrospectively determine interobserver variability of semiautomated
      volume measurements of pulmonary nodules and the potential reasons for
      variability. MATERIALS AND METHODS: The Dutch-Belgian lung cancer screening trial
      (NELSON) is a lung cancer screening study that includes men between the ages of
      50 and 75 years who are current or former heavy smokers. The NELSON project was
      approved by the Dutch Ministry of Health and the ethics committee of each
      participating hospital. Informed consent was obtained from all participants. For
      this study, the authors evaluated 1200 consecutive low-dose computed tomographic
      (CT) scans of the chest obtained during the NELSON project and identified
      subjects who had at least one 50-500-mm(3) nodule. One local and one central
      observer independently evaluated the scans and measured the volume of any
      detected nodule by using semiautomated software. Noncalcified solid nodules with
      volumes of 15-500 mm(3) were included in this study if they were fully surrounded
      by air (intraparenchymal) and were detected by both observers. The mean volume
      and the difference between both measurements were calculated for all nodules.
      Intermeasurement agreement was assessed with the Spearman correlation
      coefficient. Potential reasons for discrepancies were assessed. RESULTS: There
      were 232 men (mean age, 60 years; age range, 52-73 years) with 430 eligible
      nodules (mean volume, 77.8 mm(3); range, 15.3-499.5 mm(3)). Interobserver
      correlation was high (r = 0.99). No difference in volume was seen for 383 nodules
      (89.1%). Discrepant results were obtained for 47 nodules (10.9%); in 16 cases
      (3.7%), the discrepancy was larger than 10%. The most frequent cause of
      variability was incomplete segmentation due to an irregular shape or irregular
      margins. CONCLUSION: In a minority (approximately 11%) of small solid
      intraparenchymal nodules, semiautomated measurements are not completely
      reproducible and, thus, may cause errors in the assessment of nodule growth. For
      small or irregularly shaped nodules, an observer should check the segmentation
      shown by the program.

PMID- 16908678
TI  - Usual interstitial pneumonia and chronic idiopathic interstitial pneumonia:
      analysis of CT appearance in 92 patients.
AB  - PURPOSE: To retrospectively analyze computed tomographic (CT) findings of chronic
      idiopathic interstitial pneumonia (IIP) and to determine which findings are most
      helpful for distinguishing IIP from usual interstitial pneumonia (UIP) with
      univariate and multivariate analyses. MATERIALS AND METHODS: Institutional review
      board approval and informed consent were not required for this retrospective
      review of patient records and images. Two observers working independently and
      without knowledge of the diagnosis evaluated the extent and distribution of
      various thin-section CT findings (ground-glass opacity, consolidation,
      reticulation, and honeycombing) in 92 patients (51 men, 41 women; mean age, 56
      years; age range, 29-81 years) with a histologic diagnosis of UIP (n = 20),
      cellular nonspecific interstitial pneumonia (NSIP) (n = 16), fibrotic NSIP (n =
      16), respiratory bronchiolitis-associated interstitial lung disease (RB-ILD) (n =
      11), desquamative interstitial pneumonia (DIP) (n = 15), or lymphoid interstitial
      pneumonia (LIP) (n = 14). Observers used univariate and multivariate statistical
      analyses to compare their findings with the extent and distribution of UIP.
      RESULTS: Observers made the correct diagnosis in 145 (79%) of 184 readings.
      Multivariate logistic regression analysis showed that the independent findings
      that distinguished UIP from cellular NSIP were the extent of honeycombing and the
      most proximal bronchus with traction bronchiectasis (odds ratio, 5.16 and 0.37,
      respectively); the finding that distinguished UIP from fibrotic NSIP was the
      extent of honeycombing (odds ratio, 2.10). CT features that distinguished UIP
      from RB-ILD and DIP included extent of ground-glass opacity (odds ratio, 0.76),
      thickening of bronchovascular bundles (odds ratio, 1.58), the most proximal
      bronchus with traction bronchiectasis (odds ratio, 0.22), and the number of
      segments with traction bronchiectasis (odds ratio, 3.64). CONCLUSION: UIP has a
      characteristic appearance that usually facilitates distinction from other types
      of chronic IIPs at thin-section CT. The most useful finding when differentiating
      UIP from NSIP was the extent of honeycombing.

PMID- 16908679
TI  - Uterine fibroids: contrast-enhanced MR angiography to predict ovarian artery
      supply--initial experience.
AB  - PURPOSE: To prospectively evaluate the diagnostic performance of contrast
      material-enhanced magnetic resonance (MR) angiography in helping predict ovarian
      artery supply of uterine fibroids by using postembolization conventional
      aortography as the reference standard. MATERIALS AND METHODS: The protocol for
      the study was approved by the institutional review board, and each patient gave
      informed consent. Ninety consecutive women (mean age, 42.5 years; range, 33-63
      years) underwent MR angiography before uterine artery embolization (UAE). The
      number and origin of the ovarian arteries were determined. Ovarian artery supply
      of fibroids was graded as very unlikely, possible, or very likely by using a
      scoring system based on a combination of MR angiographic findings. MR
      angiographic results were compared with those of conventional aortography
      performed after UAE in all patients and followed by selective angiography in case
      of a suspected ovarian artery supply of fibroids. Analysis of the association
      between MR angiographic grading and conventional angiography as the standard of
      reference was performed with a chi(2) trend test. Sensitivity and specificity,
      including exact 95% confidence intervals (CIs), of MR angiography were
      determined. RESULTS: MR angiography depicted 18 ovarian arteries (four bilateral,
      10 unilateral), one with an atypical origin. Five ovarian arteries were
      classified as very likely; three, as possible; and 10, as very unlikely sources
      of arterial fibroid supply. Seven (39%) of 18 ovarian arteries detected at MR
      angiography were visible at conventional aortography. Fibroid supply was verified
      at selective angiography in five ovarian arteries in five (6%) of 90 patients.
      There was a strong association between MR angiographic grading and the results of
      conventional angiography (P = .002). Sensitivity of MR angiography in depicting
      ovarian artery supply (grade, possible or very likely) was 100% (five of five,
      95% CI: 48%; 100%) and specificity was 77% (10 of 13, 95% CI: 46%; 95%).
      CONCLUSION: Contrast-enhanced MR angiography can help predict ovarian artery
      supply of uterine fibroids.

PMID- 16908680
TI  - Pneumothorax, pleural effusion, and chest tube placement after radiofrequency
      ablation of lung tumors: incidence and risk factors.
AB  - PURPOSE: To retrospectively evaluate the incidence of and risk factors for
      pneumothorax, pleural effusion, and chest tube placement for pneumothorax after
      radiofrequency (RF) ablation of lung tumors. MATERIALS AND METHODS: Institutional
      review board approval was obtained, with waiver of informed consent. This
      retrospective study comprised 224 ablation sessions for 392 tumors in 142
      patients (92 men, 50 women; mean age, 64.0 years). Multiple variables were
      analyzed by using the Student t test or the Mann-Whitney U test for numerical
      values and by using the chi(2) test or the Fisher exact test for categorical
      values in order to assess risk factors for pneumothorax, pleural effusion, and
      chest tube placement for pneumothorax. RESULTS: The incidence of pneumothorax,
      pleural effusion, and chest tube placement for pneumothorax was 52% (117 of 224
      sessions), 19% (42 of 224 sessions), and 21% (24 of 117 sessions), respectively.
      For pneumothorax, risk factors included male sex (P = .030), no history of
      pulmonary surgery (P < .001), a greater number of tumors ablated (P < .001),
      involvement of the middle or lower lobe (P = .008), and increased length of the
      aerated lung traversed by the electrode (P = .014). For pleural effusion, risk
      factors included the use of a cluster electrode (P = .008), decreased distance to
      the nearest pleura (P = .040), and decreased length of the aerated lung traversed
      by the electrode (P = .019). For chest tube placement for pneumothorax, risk
      factors included no history of pulmonary surgery (P = .002), the use of a cluster
      electrode (P < .001), and involvement of the upper lobe (P < .001). CONCLUSION:
      Pneumothorax and pleural effusion can occur after RF ablation in patients with
      lung tumors, and chest tube placement for pneumothorax is sometimes required.

PMID- 16908681
TI  - Atrophy-hypertrophy complex in patients with cavernous transformation of the
      portal vein: CT evaluation.
AB  - PURPOSE: To retrospectively evaluate the morphologic changes in the liver
      associated with cavernous transformation of the portal vein. MATERIALS AND
      METHODS: This study was institutional review board approved. Informed patient
      consent was not required. The computed tomographic (CT) results for 22 patients
      (14 male, eight female; mean age, 54 years) with cavernous transformation of the
      portal vein and no evidence of chronic liver disease at liver biopsy were
      retrospectively reviewed and compared with the CT results for 36 control
      subjects. Various morphologic changes in the hepatic lobes were qualitatively and
      quantitatively assessed by using the Student t test for unpaired data. RESULTS:
      Qualitative analysis revealed the atrophy-hypertrophy complex in most (n = 20,
      91%) of the patients with cavernous transformation and in no control subjects.
      Atrophy of the left lateral segment and right liver lobe was seen in 16 (73%) and
      seven (32%) patients, respectively. Hypertrophy of the caudate lobe and liver
      segment IV was identified in 19 (86%) and 11 (50%) patients, respectively. All
      mean caudate lobe volume index values and mean caudate lobe-to-right lobe ratio
      values were significantly greater (P < .05) in the cavernous transformation group
      than in the control group. The mean segment IV diameter was significantly greater
      (41.6 vs 28.1 mm, P < .001) in the patients with cavernous transformation.
      Hepatic nodules and hepatic contour nodularity were not seen in the patients with
      cavernous transformation. CONCLUSION: The atrophy-hypertrophy complex is
      frequently observed in patients with cavernous transformation of the portal vein.
      Some findings, such as hypertrophy of the caudate lobe, mimic chronic liver
      disease or signs of portal hypertension, but left lateral segment atrophy and a
      normal or enlarged segment IV are distinctive findings of cavernous
      transformation.

PMID- 16908682
TI  - Prevalence and clinical importance of aortic valve calcification detected
      incidentally on CT scans: comparison with echocardiography.
AB  - PURPOSE: To evaluate retrospectively the prevalence and grade of aortic valve
      calcification incidentally detected on chest multi-detector row computed
      tomographic (CT) scans and to compare the grade of calcification with the
      severity of aortic valve disease as assessed with echocardiography. MATERIALS AND
      METHODS: Patient informed consent was waived by the institutional board on
      medical ethics that approved this study. The authors identified 402 patients (231
      men and 171 women; mean age, 62.5 years +/- 12.1) of 1820 patients who underwent
      chest multi-detector row CT between July 2001 and August 2004 and also underwent
      echocardiography. Aortic valve calcification at multi-detector row CT was
      visually graded on a scale ranging from 0 to 4 (0 = no calcification, 4 = severe
      calcification). CT findings were correlated with hemodynamic data obtained at
      echocardiography. Patients without aortic stenosis were compared with patients
      with aortic stenosis. The Student t test, Spearman correlation coefficient,
      chi(2) analysis, and an unweighted kappa test were used to compare results.
      RESULTS: Aortic valve calcification was noted on multi-detector row CT scans in
      72 of the 402 patients (18%). Twelve of 20 patients (60%) with grade 3 or grade 4
      calcification on CT scans had aortic stenosis at echocardiography, compared with
      only nine of 382 patients (2.4%) with grade 0-2 calcification (P < .001).
      Significant correlations were observed between the grade of aortic valve
      calcification and the echocardiographically determined mean (r = 0.45, P = .03)
      and peak transvalvular gradient (r = 0.47, P = .03). There was substantial
      agreement between the grade of valve calcification at multi-detector row CT and
      the severity of aortic valve disease at echocardiography (kappa = 0.67).
      CONCLUSION: Aortic valve calcification was an incidental finding on 18% of multi
      detector row CT scans. The grade of aortic valve calcification is correlated with
      the hemodynamic severity of aortic valve disease as determined with
      echocardiography.

PMID- 16908683
TI  - High-field-strength MR imaging of the liver at 3.0 T: intraindividual comparative
      study with MR imaging at 1.5 T.
AB  - PURPOSE: To prospectively evaluate whether magnetic resonance (MR) imaging of the
      liver at 3.0 T is comparable to that at 1.5 T with respect to image artifacts,
      image quality, and diagnostic utility in terms of detection and characterization
      of focal liver lesions in patients with these lesions. MATERIALS AND METHODS:
      Patients provided informed consent after the study had been explained, and the
      institutional review board approved the study protocol. An intraindividual
      comparative study was performed in 21 patients (12 men and nine women; mean age,
      58.7 years; range, 36-76 years) with a total of 79 focal liver lesions (benign
      and malignant) who were examined at 1.5- and 3.0-T MR imaging within 1 week. The
      imaging protocol consisted of T2-weighted turbo spin-echo (SE) sequences with or
      without fat suppression, as well as T1-weighted gradient-echo (GRE) sequences
      with or without gadolinium-based contrast agent. All images were rated
      independently by two radiologists with respect to types of artifacts
      (susceptibility, motion, pulsation, image homogeneity, and electrodynamic
      effects) and in regard to detectability and characterization of focal liver
      lesions. A modified sign test was used for statistical analysis (alpha < .2).
      RESULTS: Motion artifacts were significantly more pronounced in non-fat
      suppressed T2-weighted turbo SE images at 3.0 T (P = .03), whereas pulsation
      artifacts were more pronounced (P = .19) in precontrast T1-weighted GRE 1.5-T
      images. No statistically significant differences (P < .2) were observed for the
      remaining artifacts and sequences. Of the 79 index lesions, a total of 76 were
      prospectively identified at 1.5-T imaging and a total of 77 were identified at
      3.0-T imaging. CONCLUSION: MR imaging of the liver at 3.0 T, compared with that
      at 1.5 T, is feasible with equivalent image quality and diagnostic utility in
      terms of detection and characterization of focal liver lesions.

PMID- 16908685
TI  - World Health Day.

PMID- 16908686
TI  - Anomalous origin of the left main coronary artery from the main pulmonary artery
      (ALCAPA) illustrated before and after surgical correction on ECG-gated 40-slice
      computed tomography.

PMID- 16908687
TI  - Swing-like movement of pigtail catheter in a patient with ruptured chordae
      tendinae.

PMID- 16908688
TI  - Cardiac magnetic resonance directed intervention following right ventricular
      infarction.

PMID- 16908689
TI  - Huge left atrial thrombus in a patient with mitral bioprosthesis.

PMID- 16908690
TI  - Anomalous origin of right coronary artery from the mid left anterior descending
      coronary artery.

PMID- 16908691
TI  - Left atrial calcification in rheumatic heart disease: a rare presentation.

PMID- 16908692
TI  - Subacute cardiac tamponade with very large pericardial effusion in a postpartum
      woman.

PMID- 16908693
TI  - MRI of a novel passive cardiomyoplasty device: the Paracor ventricular support
      system.

PMID- 16908694
TI  - Helping the surgeon: epicardial 3D echocardiography in aortic dissection.

PMID- 16908695
TI  - Infected left ventricular pseudoaneurysm.

PMID- 16908697
TI  - Chronic post-rheumatic fever (Jaccoud's) arthropathy involving carpometacarpal
      joints.

PMID- 16908698
TI  - A guide to difficult right ventricular pacemaker lead insertion.

PMID- 16908699
TI  - Pneumopericardium following perianal fistula repair and sigmoidoscopy.

PMID- 16908700
TI  - Angioplasty and stenting to correct ostial right coronary artery obstruction by a
      prosthetic aortic valve.

PMID- 16908701
TI  - Multimodality in imaging calcific constrictive pericarditis.

PMID- 16908702
TI  - Real time three dimensional imaging of zone of ischaemia derived from surface 12
      lead ECG during percutaneous coronary revascularisation.

PMID- 16908703
TI  - A footprint of brucella infection: enormous saccular aneurysm of the ascending
      aorta.

PMID- 16908704
TI  - 64-slice cardiac computed tomography: appearance of a complex coronary to
      pulmonary arterial fistula with conus artery aneurysm.

PMID- 16908705
TI  - Relation between C reactive protein and depression remission status in patients
      presenting with acute coronary syndrome.

PMID- 16908706
TI  - Resolution of dynamic left ventricular outflow tract obstruction caused by
      retained native leaflets following mitral valve replacement using medical
      treatment.

PMID- 16908707
TI  - Myocardial late gadolinium enhancement is associated with raised serum amino
      terminal propeptide of type III collagen concentrations in patients with
      hypertrophic cardiomyopathy attributable to the Asp175Asn mutation in the alpha
      tropomyosin gene: magnetic resonance imaging study.

PMID- 16908708
TI  - Raised B-type natriuretic peptide predicts implantable cardioverter-defibrillator
      therapy in patients with ischaemic cardiomyopathy.

PMID- 16908709
TI  - Children with fulminant myocarditis rescued with extracorporeal membrane
      oxygenation.

PMID- 16908710
TI  - Pneumopericardium after bilateral lung transplantation.

PMID- 16908711
TI  - Prognostic implications of the blood pressure response to the Valsalva manoeuvre
      in elderly cardiac patients.

PMID- 16908712
TI  - Massive tear of the mitral valve after percutaneous mitral commissurotomy by live
      3D transthoracic echocardiography.

PMID- 16908713
TI  - Correlation of coronary artery bypass surgery-related myonecrosis with grafted
      vessel calibre: insights from cardiovascular magnetic resonance imaging.

PMID- 16908714
TI  - Usefulness of myocardial contrast echocardiography with nicorandil stress for the
      detection of coronary artery stenosis.

PMID- 16908715
TI  - TIMI risk score accurately risk stratifies patients with undifferentiated chest
      pain presenting to an emergency department.

PMID- 16908716
TI  - Concomitant aortic and mitral regurgitations: a rare echocardiographic view.

PMID- 16908717
TI  - Clopidogrel reduces platelet-leucocyte aggregation, monocyte activation and
      RANTES secretion in type 2 diabetes mellitus.

PMID- 16908718
TI  - Lipomatous metaplasia in myocardial infarction detected by cardiovascular
      magnetic resonance.

PMID- 16908719
TI  - Cardiac compression from a rheumatoid pericardial mass.

PMID- 16908720
TI  - Novel imaging techniques reveal the aetiology of a pseudoinfarction ECG pattern.

PMID- 16908721
TI  - Alcohol septal ablation for obstructive hypertrophic cardiomyopathy.

PMID- 16908722
TI  - Dilation of the thoracic aorta: medical and surgical management.

PMID- 16908723
TI  - Tetralogy of Fallot: from fetus to adult.

PMID- 16908724
TI  - Acceleration of stretch activation in murine myocardium due to phosphorylation of
      myosin regulatory light chain.
AB  - The regulatory light chains (RLCs) of vertebrate muscle myosins bind to the neck
      region of the heavy chain domain and are thought to play important structural
      roles in force transmission between the cross-bridge head and thick filament
      backbone. In vertebrate striated muscles, the RLCs are reversibly phosphorylated
      by a specific myosin light chain kinase (MLCK), and while phosphorylation has
      been shown to accelerate the kinetics of force development in skeletal muscle,
      the effects of RLC phosphorylation in cardiac muscle are not well understood.
      Here, we assessed the effects of RLC phosphorylation on force, and the kinetics
      of force development in myocardium was isolated in the presence of 2,3
      butanedione monoxime (BDM) to dephosphorylate RLC, subsequently skinned, and then
      treated with MLCK to phosphorylate RLC. Since RLC phosphorylation may be an
      important determinant of stretch activation in myocardium, we recorded the force
      responses of skinned myocardium to sudden stretches of 1% of muscle length both
      before and after treatment with MLCK. MLCK increased RLC phosphorylation,
      increased the Ca(2+) sensitivity of isometric force, reduced the steepness of the
      force-pCa relationship, and increased both Ca(2+)-activated and Ca(2+)
      independent force. Sudden stretch of myocardium during an otherwise isometric
      contraction resulted in a concomitant increase in force that quickly decayed to a
      minimum and was followed by a delayed redevelopment of force, i.e., stretch
      activation, to levels greater than pre-stretch force. MLCK had profound effects
      on the stretch activation responses during maximal and submaximal activations:
      the amplitude and rate of force decay after stretch were significantly reduced,
      and the rate of delayed force recovery was accelerated and its amplitude reduced.
      These data show that RLC phosphorylation increases force and the rate of cross
      bridge recruitment in murine myocardium, which would increase power generation in
      vivo and thereby enhance systolic function.

PMID- 16908725
TI  - Molecular template for a voltage sensor in a novel K+ channel. I. Identification
      and functional characterization of KvLm, a voltage-gated K+ channel from Listeria
      monocytogenes.
AB  - The fundamental principles underlying voltage sensing, a hallmark feature of
      electrically excitable cells, are still enigmatic and the subject of intense
      scrutiny and controversy. Here we show that a novel prokaryotic voltage-gated
      K(+) (Kv) channel from Listeria monocytogenes (KvLm) embodies a rudimentary, yet
      robust, sensor sufficient to endow it with voltage-dependent features comparable
      to those of eukaryotic Kv channels. The most conspicuous feature of the KvLm
      sequence is the nature of the sensor components: the motif is recognizable; it
      appears, however, to contain only three out of eight charged residues known to be
      conserved in eukaryotic Kv channels and accepted to be deterministic for folding
      and sensing. Despite the atypical sensor sequence, flux assays of KvLm
      reconstituted in liposomes disclosed a channel pore that is highly selective for
      K(+) and is blocked by conventional Kv channel blockers. Single-channel currents
      recorded in symmetric K(+) solutions from patches of enlarged Escherichia coli
      (spheroplasts) expressing KvLm showed that channel open probability sharply
      increases with depolarization, a hallmark feature of Kv channels. The
      identification of a voltage sensor module in KvLm with a voltage dependence
      comparable to that of other eukaryotic Kv channels yet encoded by a sequence that
      departs significantly from the consensus sequence of a eukaryotic voltage sensor
      establishes a molecular blueprint of a minimal sequence for a voltage sensor.

PMID- 16908726
TI  - Molecular template for a voltage sensor in a novel K+ channel. II. Conservation
      of a eukaryotic sensor fold in a prokaryotic K+ channel.
AB  - KvLm, a novel bacterial depolarization-activated K(+) (Kv) channel isolated from
      the genome of Listeria monocytogenes, contains a voltage sensor module whose
      sequence deviates considerably from the consensus sequence of a Kv channel sensor
      in that only three out of eight conserved charged positions are present.
      Surprisingly, KvLm exhibits the steep dependence of the open channel probability
      on membrane potential that is characteristic of eukaryotic Kv channels whose
      sensor sequence approximates the consensus. Here we asked if the KvLm sensor
      shared a similar fold to that of Shaker, the archetypal eukaryotic Kv channel, by
      examining if interactions between conserved residues in Shaker known to mediate
      sensor biogenesis and function were conserved in KvLm. To this end, each of the
      five non-conserved residues in the KvLm sensor were mutated to their Shaker-like
      charged residues, and the impact of these mutations on the voltage dependence of
      activation was assayed by current recordings from excised membrane patches of
      Escherichia coli spheroplasts expressing the KvLm mutants. Conservation of
      pairwise interactions was investigated by comparison of the effect of single
      mutations to the impact of double mutations presumed to restore wild-type fold
      and voltage sensitivity. We observed significant functional coupling between
      sites known to interact in Shaker Kv channels, supporting the notion that the
      KvLm sensor largely retains the fold of its eukaryotic homologue.

PMID- 16908727
TI  - Reversal of HCN channel voltage dependence via bridging of the S4-S5 linker and
      Post-S6.
AB  - Voltage-gated ion channels possess charged domains that move in response to
      changes in transmembrane voltage. How this movement is transduced into gating of
      the channel pore is largely unknown. Here we show directly that two functionally
      important regions of the spHCN1 pacemaker channel, the S4-S5 linker and the C
      linker, come into close proximity during gating. Cross-linking these regions with
      high-affinity metal bridges or disulfide bridges dramatically alters channel
      gating in the absence of cAMP; after modification the polarity of voltage
      dependence is reversed. Instead of being closed at positive voltage and
      activating with hyperpolarization, modified channels are closed at negative
      voltage and activate with depolarization. Mechanistically, this reversal of
      voltage dependence occurs as a result of selectively eliminating channel
      deactivation, while retaining an existing inactivation process. Bridging also
      alters channel activation by cAMP, showing that interaction of these two regions
      can also affect the efficacy of physiological ligands.

PMID- 16908728
TI  - High-dose cyclophosphamide for moderate to severe refractory multiple sclerosis.
AB  - BACKGROUND: High-dose cyclophosphamide is active in immune-mediated illnesses.
      OBJECTIVE: To describe the effects of high-dose cyclophosphamide on severe
      refractory multiple sclerosis. DESIGN, SETTING, AND PATIENTS: Patients with
      multiple sclerosis with an Expanded Disability Status Scale (EDSS) score of 3.5
      or higher after 2 or more Food and Drug Administration-approved disease-modifying
      therapy regimens were evaluated. INTERVENTIONS: Patients received 200 mg/kg of
      cyclophosphamide over 4 days. MAIN OUTCOME MEASURES: Patients had brain magnetic
      resonance imaging and neuro-ophthalmologic evaluations every 6 months and
      quarterly EDSS and quality-of-life evaluations for 2 years. RESULTS: Twelve
      patients were evaluated for clinical response (median follow-up, 15.0 months;
      follow-up range, 6-24 months). During follow-up, no patients increased their
      baseline EDSS scores by more than 1.0. Five patients decreased their EDSS scores
      by 1.0 or more (EDSS score decrease range, 1.0-5.0). Two of 11 patients had a
      single enhancing lesion at baseline; these lesions resolved after high-dose
      cyclophosphamide treatment. At 12 months, 1 patient showed 1 new enhancing lesion
      without a corresponding high-intensity T2-weighted or fluid-attenuated inversion
      recovery signal. Patients reported improvement in all of the quality-of-life
      parameters measured. Neurologic improvement involved changes in gait, bladder
      control, and visual function. Treatment response was seen regardless of the
      baseline presence or absence of contrast lesion activity. Patient quality-of-life
      improvement occurred independently of EDSS score changes. In this small group of
      patients with treatment-refractory multiple sclerosis, high-dose cyclophosphamide
      was associated with minimal morbidity and improved clinical outcomes.
      CONCLUSIONS: High-dose cyclophosphamide treatment in patients with severe
      refractory multiple sclerosis can result in disease stabilization, improved
      functionality, and improved quality of life. Further studies are necessary to
      determine the most appropriate patients for this treatment.

PMID- 16908729
TI  - Peripheral neuropathy with impaired glucose tolerance: a sweet smell of success?

PMID- 16908730
TI  - Argatroban tPA stroke study: study design and results in the first treated
      cohort.
AB  - BACKGROUND: The benefit of intravenous recombinant tissue plasminogen activator
      (rtPA) in acute stroke is linked to clot lysis and artery recanalization.
      Argatroban is a direct thrombin inhibitor that safely augments the benefit of
      rtPA in animal stroke models. There are no human data on this combination.
      DESIGN: We report the first phase of the Argatroban tPA Stroke Study, an ongoing
      prospective, open-label, dose-escalation, safety and activity study of argatroban
      and rtPA in patients with ischemic stroke. The primary outcome was incidence of
      intracerebral hemorrhage; secondary outcome, complete recanalization at 2 hours.
      After standard-dose intravenous rtPA administration, a 100-mug/kg bolus of
      argatroban followed by infusion of 1 mug/kg per minute for 48 hours was adjusted
      to a target partial thromboplastin time of 1.75 times that of the control group.
      RESULTS: Fifteen patients (including 10 men) were enrolled, with a mean +/- SD
      age of 61 +/- 13 years. All patients had middle cerebral artery occlusions.
      Baseline median National Institute of Health Stroke Scale score was 14 (range, 4
      25). The mean +/- SD time from symptom onset to argatroban bolus administration
      was 172 +/- 53 minutes. Symptomatic intracerebral hemorrhage occurred in 2
      patients, including 1 with parenchymal hemorrhage type 2. Asymptomatic bleeding
      occurred in 1 patient and there was 1 death. Recanalization was complete in 6
      patients and partial in another 4, and reocclusion occurred in 3 within 2 hours
      of rtPA bolus administration. CONCLUSION: The safety of low-dose argatroban
      combined with intravenous rtPA may be within acceptable limits, and its efficacy
      for producing fast and complete recanalization is promising, but a larger cohort
      of patients is required to confirm these preliminary observations.

PMID- 16908731
TI  - Plasma exchange in neuroimmunological disorders: part 2. Treatment of
      neuromuscular disorders.
AB  - Plasma exchange is a well-established therapeutic procedure commonly used in many
      neurological disorders of autoimmune etiology. In this second part of our review,
      we assess the role of plasma exchange in the treatment of neuromuscular
      disorders. In Guillain-Barre syndrome and other immune-mediated neuropathic
      disorders, randomized controlled trials have demonstrated the therapeutic
      efficacy of plasma exchange. Myasthenia gravis and Lambert-Eaton syndrome
      represent neuromuscular disorders where plasmapheresis might be of potential
      efficacy.

PMID- 16908732
TI  - Achieving target cholesterol goals after stroke: is in-hospital statin initiation
      the key?
AB  - BACKGROUND: National advisories recommend statin therapy as an element of
      secondary prevention for patients with ischemic stroke or transient ischemic
      attack of atherosclerotic origin. Statins are of proven benefit in persons at
      high risk of vascular disease. OBJECTIVES: To evaluate the effects of in-hospital
      initiation of statins on 3-month treatment adherence rates and achievement of
      national guideline target cholesterol goals. METHODS: Data were collected in
      consecutively encountered patients with ischemic stroke or transient ischemic
      attack admitted to a university hospital stroke service beginning September 1,
      2002. Patients were included in the study if they were not receiving a statin
      before admission and had an indication for statin therapy. Adherence to statin
      treatment and achievement of national guideline target cholesterol goals were
      assessed 3 months after discharge. RESULTS: From September 1, 2002, through April
      30, 2005, 92 (17%) of 552 individuals met the study criteria. Hospital initiation
      of statin therapy yielded high rates of adherence (93% [86/92]), lowered mean low
      density lipoprotein cholesterol levels from 120 to 78 mg/dL (3.1 to 2.0 mmol/L;
      P<.001), and increased the proportion of patients with low-density lipoprotein
      cholesterol levels lower than 100 mg/dL (2.6 mmol/L) from 36% to 88% (P<.001) at
      3 months. CONCLUSIONS: Statin initiation during hospitalization for an ischemic
      cerebrovascular event is associated with high rates of adherence to treatment,
      lowering of low-density lipoprotein cholesterol levels, and higher rates of
      achieving national cholesterol guidelines.

PMID- 16908733
TI  - Dietary copper and high saturated and trans fat intakes associated with cognitive
      decline.
AB  - BACKGROUND: Evidence from prospective epidemiologic studies and animal models
      suggests that intakes of dietary fats and copper may be associated with
      neurodegenerative diseases. OBJECTIVE: To examine whether high dietary copper
      intake is associated with increased cognitive decline among persons who also
      consume a diet high in saturated and trans fats. DESIGN: Community-based
      prospective study. SETTING: Chicago, Ill. Patients Chicago residents 65 years and
      older. MAIN OUTCOME MEASURES: Cognitive function was assessed using 4 cognitive
      tests administered during in-home interviews at 3-year intervals for 6 years.
      Dietary assessment was performed with a food frequency questionnaire. Dietary
      intakes of copper and fats were related to change in global cognitive score (the
      mean of the 4 tests) among 3718 participants. RESULTS: Among persons whose diets
      were high in saturated and trans fats, higher copper intake was associated with a
      faster rate of cognitive decline. In multiple-adjusted mixed models, the
      difference in rates for persons in the highest (median, 2.75 mg/d) vs lowest
      (median, 0.88 mg/d) quintiles of total copper intake was -6.14 standardized units
      per year (P<.001) or the equivalent of 19 more years of age. There was also a
      marginally statistically significant association (P = .07) with the highest
      quintile of food intake of copper (median, 1.51 mg/d) and a strong dose-response
      association with higher copper dose in vitamin supplements. Copper intake was not
      associated with cognitive change among persons whose diets were not high in these
      fats. CONCLUSION: These data suggest that high dietary intake of copper in
      conjunction with a diet high in saturated and trans fats may be associated with
      accelerated cognitive decline.

PMID- 16908734
TI  - Subthalamic stimulation in Parkinson disease: behavior and social adaptation.
AB  - BACKGROUND: Bilateral subthalamic high-frequency stimulation significantly
      improves motor functions in patients with advanced forms of Parkinson disease
      (PD). This favorable effect contrasts with a growing number of reports that the
      treatment may result in psychiatric complications. OBJECTIVE: To analyze the
      presence of behavioral disorders and social maladjustment in PD patients
      successfully treated with continuous bilateral subthalamic stimulation. DESIGN:
      Prospective study. SETTING: University hospital. METHODS: Twenty PD patients
      underwent prospective evaluation for behavioral and personality changes, quality
      of life, and social functioning, 6 and 24 months after surgery to implant
      bilateral stimulating electrodes within the subthalamic nucleus. RESULTS: At 6
      and 24 months after surgery, parkinsonian motor disability (on-stimulation/off
      medication) was improved by 81% and 67%, respectively, and the severity of
      levodopa-related motor complications was improved by 84% and 70%, respectively.
      Levodopa-equivalent dosage was decreased by 79% and 66%, respectively; severity
      of depression was improved by 21% and 33%, respectively; and severity of anxiety
      was improved by 43% and 64%, respectively. The patients' personality traits were
      unmodified. Twenty-four months after surgery, the global score for quality of
      life was improved by 28%, whereas scores for social adjustment remained stable.
      CONCLUSIONS: Provided that patients with PD are rigorously selected for
      neurosurgery, subthalamic stimulation (1) improves mood, anxiety, and quality of
      life; (2) does not result in severe permanent psychiatric disorders or modify
      patients' personality; and (3) does not ameliorate social adaptation.

PMID- 16908735
TI  - Common misdiagnosis of a common neurological disorder: how are we misdiagnosing
      essential tremor?
AB  - BACKGROUND: As a common neurological disorder, the diagnosis of essential tremor
      (ET) is considered routine. Despite this, previous work suggests that
      misdiagnoses may be common. Among other things, these misdiagnoses can lead to
      treatment errors. OBJECTIVES: To estimate how often other tremor disorders are
      misdiagnosed as ET and to identify factors that increase the odds of
      misdiagnosing ET and to precisely quantify the extent to which they do so.
      DESIGN: Seventy-one consecutive patients underwent an evaluation at the
      Neurological Institute of New York, New York, between January 1, 2000, and
      December 31, 2005; these patients had a pre-evaluation diagnosis of ET. The
      criteria for ET were adapted from the consensus statement of the Movement
      Disorder Society. RESULTS: Twenty-six patients (37%) were misdiagnosed as having
      ET ("false ET"). Their true diagnoses were Parkinson disease (11 patients [15%]),
      dystonia (6 patients [8%]), Parkinson disease with ET (5 patients [7%]), and
      other disorders (4 patients [6%]). Factors associated with misdiagnosed ET
      included unilateral arm tremor (odds ratio, 10.5; 95% confidence interval, 1.2
      95.4; P=.02), spooning of the hands and other dystonic postures (odds ratio,
      16.3; 95% confidence interval, 4.0-66.4; P<.001), and other unusual features
      (isolated thumb tremor, isolated leg tremor, and non-rhythmic tremor) (odds
      ratio, 49.4; 95% confidence interval, 2.7-895.0; P<.001). CONCLUSIONS: About 1 in
      3 patients with tremor was misdiagnosed as having ET, with the most frequent
      false diagnoses being Parkinson disease and dystonia. Several factors that
      increased the odds of misdiagnosing ET were identified. These factors could be
      incorporated into improved diagnostic algorithms.

PMID- 16908736
TI  - Race/ethnicity, sex, and socioeconomic status as predictors of outcome after
      surgery for temporal lobe epilepsy.
AB  - BACKGROUND: Several risk factors have been attributed to seizure recurrence after
      surgery. It is unknown whether race/ethnicity plays a role in outcome. OBJECTIVE:
      To evaluate whether race/ethnicity plays a role in seizure recurrence after
      surgery. DESIGN: Cohort study. SETTING: We evaluated data obtained from the
      epilepsy centers at the University of Alabama at Birmingham and New York
      University, New York, NY. PATIENTS: All patients included had a diagnosis of
      mesial temporal sclerosis and underwent temporal lobectomy. MAIN OUTCOME
      MEASURES: Occurrence of seizure after surgery was registered 1 year after
      surgery. We used multiple logistic regression analysis to model the presence of
      seizure recurrence after surgery and generated odds ratios (ORs) for seizure
      recurrence after surgery for African American and Hispanic patients relative to
      white patients. An unadjusted model incorporated only race/ethnicity as the
      independent variable, and an adjusted model included socioeconomic status, age,
      duration of epilepsy, education, history of febrile seizures, sex, handedness,
      lateralization of epileptogenic focus, and number of antiepileptics as the
      independent variables. RESULTS: Two hundred fifty-two patients underwent surgical
      treatment with pathological confirmation of mesial temporal sclerosis. No
      differences were found between racial/ethnic groups in terms of seizure
      recurrence in any models. For African American patients, the ORs were 0.9 (95%
      confidence interval [CI], 0.4-2.1) for the unadjusted model and 0.8 (95% CI, 0.3
      2.0) for the adjusted model; for Hispanic patients, the ORs were 1.6 (95% CI, 0.8
      3.2) for the unadjusted model and 1.1 (95% CI, 0.5-2.6) for the adjusted model,
      relative to white patients. CONCLUSION: Our data suggest that although sex
      appears to play a role in the outcomes of surgery for temporal lobe epilepsy,
      race and socioeconomic status do not.

PMID- 16908737
TI  - Spinal cord ischemia: clinical and imaging patterns, pathogenesis, and outcomes
      in 27 patients.
AB  - BACKGROUND: The natural history and pathogenesis of ischemic spinal cord
      infarction remain largely unknown because most clinical studies have included
      mostly patients with ischemic lesions associated with aortic surgery or prolonged
      arterial hypotension. OBJECTIVE: To assess the pathogenetic mechanisms and
      outcomes of these cord infarctions based on clinical findings and spinal vascular
      anatomy. DESIGN: Retrospective review. PATIENTS: We analyzed the clinical,
      laboratory, imaging, and outcome data for 27 patients with acute spinal cord
      infarction admitted between 1990 and 2003. There were 11 men and 16 women (age
      range, 19-80 years [mean age, 56 years]). RESULTS: Ten patients had anterior
      spinal artery patterns, 4 each had anterior and posterior unilateral patterns, 3
      had central patterns, and 2 each had posterior spinal artery patterns, transverse
      syndromes, and unclassifiable clinical pictures. Twenty patients had no
      identifiable etiology. Patients with a central or transverse infarct showed a
      high frequency of peripheral vascular disease, and all transverse infarcts
      occurred following prolonged arterial hypotension. The onset of all other
      infarcts was associated with mechanical triggering movements (P = .02), and these
      patients frequently had diseases of the spine (P = .003) at the level of the
      spinal lesion, with the clinical data suggesting root involvement at the level of
      the spinal cord lesion and pointing to mechanical injury of a radicular artery.
      The outcomes were favorable, with only 13 patients showing significant gait
      impairment on leaving the hospital. CONCLUSIONS: There are 2 main types of spinal
      cord ischemia: (1) radicular artery territory infarct (bilateral anterior or
      posterior spinal artery infarcts and unilateral infarcts) and (2) extensive
      spinal cord hypoperfusion (central and transverse infarcts). Each type has
      characteristic clinical, imaging, pathogenetic, and prognostic features.

PMID- 16908738
TI  - Clinical spectrum of mitochondrial DNA depletion due to mutations in the
      thymidine kinase 2 gene.
AB  - BACKGROUND: Mitochondrial DNA depletion syndrome is an autosomal recessive
      disorder characterized by decreased mitochondrial DNA copy numbers in affected
      tissues. It has been linked to 4 genes involved in deoxyribonucleotide
      triphosphate metabolism: thymidine kinase 2 (TK2), deoxyguanosine kinase (DGUOK),
      polymerase gamma (POLG), and SUCLA2, the gene encoding the beta-subunit of the
      adenosine diphosphate-forming succinyl coenzyme A synthetase ligase. OBJECTIVE:
      To highlight the variability in the clinical spectrum of TK2-related
      mitochondrial DNA depletion syndrome. DESIGN: Review of patients and the
      literature. SETTING: Tertiary care university. PATIENTS: Four patients with
      mitochondrial DNA depletion syndrome and mutations in the TK2 gene. MAIN OUTCOME
      MEASURES: Definition of clinical variability. RESULTS: Patient 1 had evidence of
      lower motoneuron disease and was initially diagnosed as having spinal muscular
      atrophy type 3. Patient 2, who is alive and ambulatory at age 9 years, presented
      at age 2 years with a slowly progressive mitochondrial myopathy. Patient 3 had a
      more severe myopathy, with onset in infancy and death at age 6 years of
      respiratory failure. Patient 4 had a rapidly progressive congenital myopathy with
      rigid spine syndrome and he died at age 19 months. CONCLUSION: The clinical
      spectrum of TK2 mutations is not limited to severe infantile myopathy with motor
      regression and early death but includes spinal muscular atrophy type 3-like
      presentation, rigid spine syndrome, and subacute myopathy without motor
      regression and with longer survival.

PMID- 16908739
TI  - Hepatocerebral mitochondrial DNA depletion syndrome caused by deoxyguanosine
      kinase (DGUOK) mutations.
AB  - BACKGROUND: Autosomal recessive mutations in deoxyguanosine kinase (DGUOK) have
      been identified in the hepatocerebral form of mitochondrial DNA (mtDNA) depletion
      syndrome. OBJECTIVES: To describe the clinical spectrum of DGUOK-related mtDNA
      depletion syndrome in 6 children and to summarize the literature. RESULTS: We
      identified pathogenic mutations in DGUOK in 6 children with the hepatocerebral
      form of mtDNA depletion syndrome. We describe the clinical, neuroradiologic,
      histologic, and genetic features in these children. All children showed severe
      hepatopathy, while involvement of other organs (skeletal muscle and brain) was
      variable. We identified 5 novel mutations (1 of them in 2 children) and 2
      previously described mutations. Three different mutations affected the initial
      methionine, suggesting a mutational hot spot. One of our patients underwent liver
      transplantation; pathologic findings revealed (in addition to diffuse
      hepatopathy) a hepatocellular carcinoma, implying a possible link between mtDNA
      depletion syndrome and tumorigenesis. CONCLUSION: We studied 12 children with
      infantile hepatoencephalopathies and mtDNA depletion syndrome and found
      pathogenic DGUOK mutations in 6, suggesting that this gene defect is a frequent
      but not an exclusive cause of the hepatic form of mtDNA depletion syndrome.

PMID- 16908740
TI  - Fragile X premutation with atypical symptoms at onset.
AB  - OBJECTIVE: To evaluate the presence of carriers of the fragile X premutation
      among male patients with sporadic ataxia without expansion into known
      spinocerebellar ataxia genes. DESIGN: Clinical and genetic examinations were
      performed on patients with sporadic pure ataxia and patients with ataxia
      associated with extracerebellar features such as pyramidal and extrapyramidal
      signs, dementia, or peripheral neuropathy. SETTING: University department of
      neurology. PATIENTS: One hundred forty-two Italian men with sporadic ataxia with
      onset at age 30 to 84 years. INTERVENTIONS: The CGG repeat size of the FMR1 gene
      was evaluated with fluorescent polymerase chain reaction. Premutated allele
      lengths were confirmed with Southern blot analysis. RESULTS: FMR1 premutation
      alleles with a repeat number greater than 55 were detected in 3 probands (2.1%)
      from a total of 142 male subjects initially referred to our university medical
      center for evaluation of sporadic ataxia. Two patients had typical fragile X
      syndrome with associated tremor or ataxia, and the third patient had spastic
      paraparesis without clear symptoms of cerebellar ataxia and without the common
      signs seen at magnetic resonance imaging. CONCLUSIONS: Genetic analysis of the
      FMR1 gene could provide a reliable diagnostic tool for the definitive diagnosis
      of late-onset ataxias. Additional studies are needed to clarify the importance of
      premutation screening in patients with movement disorders or other associated
      atypical features at onset, such as paraparesis.

PMID- 16908741
TI  - Slower disease progression and prolonged survival in contemporary patients with
      amyotrophic lateral sclerosis: is the natural history of amyotrophic lateral
      sclerosis changing?
AB  - BACKGROUND: In recent years, considerable effort has been made to improve the
      treatment of patients with amyotrophic lateral sclerosis (ALS). However, despite
      the increased use of supportive measures, controversy still exists about overall
      trends in disease progression and survival. OBJECTIVE: To analyze whether
      survival and disease progression in patients with ALS have changed during the
      past 20 years. DESIGN: By using the Kaplan-Meier life-table method, we compared
      disease progression (measured as time to a 20-point increase in the Appel ALS
      score) and survival in 1041 patients diagnosed as having ALS between January 1,
      1984, and January 1, 1999 (historical group, n = 647), and between January 2,
      1999, and November 1, 2004 (contemporary group, n = 394). The Cox proportional
      hazards model was used for univariate and multivariate analyses. RESULTS: The
      median survival from symptom onset was 4.32 years (95% confidence interval [CI],
      3.81-4.84 years) in the contemporary group compared with 3.22 years (95% CI, 3.04
      3.41 years) in the historical group (P<.001). The contemporary patients
      progressed more slowly (10 months to a 20-point increase; 95% CI, 9-13 months)
      compared with patients in the historical group (9 months to a 20-point increase;
      95% CI, 8-9 months) (P<.001). In the multivariate Cox proportional hazards model,
      the observed outcome improvement over time was independent of confounding
      factors, such as age, sex, diagnostic delay, site of symptom onset, baseline
      forced vital capacity, and baseline Appel ALS score, and independent of the use
      of potentially outcome-modifying therapies (riluzole, noninvasive ventilation,
      and percutaneous gastrostomy). CONCLUSIONS: Contemporary patients had
      significantly prolonged survival and slower disease progression compared with
      patients from the historical group. The improved outcome seemed independent of
      specific ALS outcome-modifying therapies, but we cannot rule out an effect of
      comorbid conditions, which could have influenced medical treatment and survival.
      Nevertheless, our observations suggest the possibility that disease course has
      changed and that ALS is becoming less aggressive over time. Further studies are
      needed to determine whether there has been a fundamental change in the natural
      history of the disease or whether our results are because of other unmeasured
      aspects of improved multidisciplinary care.

PMID- 16908742
TI  - Detection of cerebral degeneration in amyotrophic lateral sclerosis using high
      field magnetic resonance spectroscopy.
AB  - BACKGROUND: Clinical assessment is insensitive to the degree of cerebral
      involvement in amyotrophic lateral sclerosis (ALS). Regional brain concentrations
      N-acetylaspartylglutamate (NAA) plus myo-inositol (Ins), as measured by magnetic
      resonance spectroscopy, are respectively decreased and increased, suggesting that
      these compounds may provide a biomarker of the degree of cerebral involvement in
      ALS. OBJECTIVE: To test the hypothesis that the NAA/Ins ratio may provide an
      index of cerebral involvement in patients with ALS. DESIGN: High-field (3.0-T)
      magnetic resonance spectroscopy was performed to determine the NAA/creatine plus
      phosphocreatine (NAA/Cr), NAA/choline (NAA/Cho), Ins/Cr, and NAA/Ins ratios in
      the motor cortex. PARTICIPANTS: Seventeen patients with ALS and 15 healthy
      control subjects were studied. RESULTS: In patients with ALS, the greatest
      abnormality was a 22% decrease in NAA/Ins (71% sensitivity and 93% specificity, P
      = .001); Ins/Cr was increased 18% (88% sensitivity and 53% specificity, P = .04),
      NAA/Cr was decreased 10% (88% sensitivity and 47% specificity, P = .04), and
      NAA/Cho was decreased 14% (53% sensitivity and 87% specificity, P = .047).
      Correlation of the ALS Functional Rating Scale with NAA/Ins approached
      statistical significance (R = 0.43, P = .07). CONCLUSION: The NAA/Ins ratio may
      provide a meaningful biomarker in ALS given its optimal sensitivity and
      specificity profile.

PMID- 16908743
TI  - Laboratory abnormalities in ambulatory patients with myotonic dystrophy type 1.
AB  - BACKGROUND: Myotonic dystrophy type 1 (DM1) is the most prevalent form of adult
      muscular dystrophy worldwide. Although well known for the classic manifestations
      of myotonia, weakness, and early cataracts, it has broad effects on multiple
      organ systems. OBJECTIVE: To analyze and compile the laboratory abnormalities of
      126 adult patients with DM1. DESIGN: Laboratory data obtained before treatment
      were compiled and include values for 45 different laboratory tests and 2860 total
      studies. SETTING: University hospital. PATIENTS: One hundred twenty-six medically
      healthy, mild to moderately affected, ambulatory patients with DM1 and good
      venous access enrolled in one of 12 major DM1 clinical trials at a university
      hospital from 1975 to 2005. RESULTS: Of the 2860 laboratory studies, results for
      470 (16.4%) were outside their reference ranges. Of the 45 types of laboratory
      tests studied, 41 demonstrated abnormal findings. The relative frequency of an
      abnormally elevated laboratory value was greater than 50% in several tests,
      including levels of hemoglobin A(1c), follicle-stimulating hormone, luteinizing
      hormone in men, and gamma-glutamyltransferase and creatine kinase in women. In
      addition, levels of lactate dehydrogenase in men and hemoglobin in women were
      abnormally high or low in more than 50% of the test results evaluated.
      CONCLUSION: There is a high frequency of abnormal laboratory values in DM1 that
      may form a basis for early screening and monitoring and provide insight into the
      spectrum of tissues involved in this disease.

PMID- 16908744
TI  - Topography of dopamine transporter availability in progressive supranuclear
      palsy: a voxelwise [123I]beta-CIT SPECT analysis.
AB  - BACKGROUND: Dopaminergic loss can be visualized by means of iodine I 123-labeled
      2beta-carbomethoxy-3beta-(4-iodophenyl)tropane ([(123)I]beta-CIT) single-photon
      emission computed tomography (SPECT) in several neurodegenerative parkinsonian
      disorders. Most previous SPECT studies have adopted region-of-interest methods
      for analysis, which are subjective and operator dependent. OBJECTIVE: To
      objectively localize the cerebral dopamine transporter status in the early stages
      of progressive supranuclear palsy (PSP). DESIGN: Prospective study. SETTING:
      Parkinson disease outpatient clinic. PATIENTS: Fourteen patients with PSP, 17
      with Parkinson disease (PD), 15 with Parkinson-variant multiple-system atrophy
      (MSA-P), and 13 healthy control subjects, matched for age and disease duration.
      INTERVENTIONS: Statistical parametric mapping applied to [(123)I]beta-CIT SPECT.
      MAIN OUTCOME MEASURES: Differences in [(123)I]beta-CIT uptake. RESULTS: All
      patients with the different parkinsonian disorders showed a significant decrease
      in striatal [(123)I]beta-CIT uptake without any overlap with the control group.
      In patients with MSA-P and PSP, an additional reduction in brainstem [(123)I]beta
      CIT signal compared with controls and patients with PD was identified with
      statistical parametric mapping. Midbrain [(123)I]beta-CIT uptake discriminated
      atypical parkinsonian disorders from PD with an overall correct classification of
      91.3%. On the other hand, [(123)I]beta-CIT SPECT failed to discriminate PSP and
      MSA-P. CONCLUSION: By applying statistical parametric mapping to [(123)I]beta-CIT
      SPECT images of patients with PSP, a widespread decline of monoaminergic
      transporter availability including the striatum and brainstem was localized in
      PSP, discriminating patients with PSP from patients with PD, but not from those
      with MSA-P. Quantification of midbrain dopamine transporter signal may therefore
      enhance the utility of SPECT imaging in the differential diagnosis of patients
      with parkinsonism.

PMID- 16908745
TI  - Altered vascular phenotype in autism: correlation with oxidative stress.
AB  - BACKGROUND: Autism is a neurologic disorder characterized by impaired
      communication and social interaction. Results of previous studies showed
      biochemical evidence for abnormal platelet reactivity and altered blood flow in
      children with autism. OBJECTIVE: To evaluate the vascular phenotype in children
      with autism. DESIGN AND MAIN OUTCOME MEASURES: Urinary levels of isoprostane
      F(2alpha)-VI, a marker of lipid peroxidation; 2,3-dinor-thromboxane B(2), which
      reflects platelet activation; and 6-keto-prostaglandin F(1alpha), a marker of
      endothelium activation, were measured by means of gas chromatography-mass
      spectrometry in subjects with autism and healthy control subjects. SETTING AND
      SUBJECTS: Children with a clinical diagnosis of autism attending the Pfeiffer
      Treatment Center. RESULTS: Compared with controls, children with autism had
      significantly higher urinary levels of isoprostane F(2alpha)-VI, 2,3-dinor
      thromboxane B(2), and 6-keto-prostaglandin F(1alpha). Lipid peroxidation levels
      directly correlated with both vascular biomarker ratios. CONCLUSION: Besides
      enhanced oxidative stress, platelet and vascular endothelium activation also
      could contribute to the development and clinical manifestations of autism.

PMID- 16908746
TI  - Tumor necrosis factor alpha and interleukin 10 promoter region polymorphisms and
      risk of late-onset Alzheimer disease.
AB  - BACKGROUND: Functional polymorphisms in tumor necrosis factor alpha (TNF-alpha)
      and interleukin 10 (IL-10) can affect immune response, inflammation, tissue
      injury, and possibly the susceptibility to Alzheimer disease (AD). OBJECTIVE: To
      evaluate the association between promoter region polymorphisms in the TNF-alpha
      and IL-10 genes and risk of late-onset AD in older white subjects. DESIGN:
      Community-based case-control study. SETTING: Group Health Cooperative of Puget
      Sound. PARTICIPANTS: White subjects (n = 265) meeting criteria for probable or
      definite AD (cases) and white control subjects (n = 347) (controls). MAIN OUTCOME
      MEASURES: Genotyping results for TNF-alpha, IL-10, and apolipoprotein E (APOE)
      genotyping. RESULTS: The TNF-alpha -863 A allele was associated with reduced odds
      of developing AD, and the test for trend suggested that having 2 copies of the A
      allele further reduces the risk (odds ratios [C/C, reference], 0.66 for C/A and
      0.58 for A/A; P = .04). Because of linkage disequilibrium in the TNF-alpha
      region, we constructed promoter region haplotypes as defined by single nucleotide
      polymorphisms at positions -863 and -308. Based on knowledge of TNF-alpha protein
      production, we ordered the haplotypes based on apparent increasing
      transcriptional activity. After adjusting for age, education, and the presence of
      the APOE epsilon4 genotype, the test for trend showed increasing odds of AD with
      increasing transcriptional activity (P = .02). The IL-10 -1082 and IL-10 -592
      allele and genotype frequencies were not significantly different between cases
      and controls. CONCLUSION: Variation in the TNF-alpha promoter region, or possibly
      polymorphisms in nearby genes, could affect cerebral inflammatory response and
      the risk of late-onset AD.

PMID- 16908747
TI  - Clinical features and gene analysis in Korean patients with early-onset Parkinson
      disease.
AB  - BACKGROUND: Systematic analysis of clinical features and gene mutations has not
      been performed in Korean patients with early-onset Parkinson disease (PD).
      OBJECTIVE: To investigate the clinical characteristics and genetic background of
      Korean patients with early-onset PD. DESIGN: Clinical and genetic study. SETTING:
      University hospital. PATIENTS: Ninety-four patients with early-onset PD (mean +/-
      SD age at onset, 39.8 +/- 7.3 years) of 1100 patients with PD. INTERVENTIONS:
      Analysis of clinical characteristics and mutation analysis of the parkin and PTEN
      induced kinase (PINK1) genes by direct sequencing and gene-dosage analysis using
      the multiplex ligation-dependent probe amplification technique. MAIN OUTCOME
      MEASURES: The correlation between age at onset and clinical characteristics and
      the clinical features of patients with onset before age 30 years vs patients with
      onset after age 30 years. RESULTS: Because age at onset was younger, levodopa
      induced dyskinesia and off-dystonia were more frequently observed (P=.008).
      Patients affected before age 30 years showed more frequent levodopa-induced
      dyskinesia and off-dystonia (P=.002). We identified 3 patients (5%) with parkin
      gene mutations but none with the PINK1 mutation. CONCLUSIONS: Earlier onset of
      levodopa-induced dyskinesia and off-dystonia were characteristic features of
      early-onset PD, especially before an onset age of 30 years. However, parkin gene
      mutations were less frequent in these patients than in Japanese groups reported
      elsewhere.

PMID- 16908748
TI  - Regional gray matter atrophy in early primary progressive multiple sclerosis: a
      voxel-based morphometry study.
AB  - BACKGROUND: Gray matter (GM) atrophy has been reported in multiple sclerosis
      (MS). However, little is known about its regional distribution. OBJECTIVE: To
      investigate the regional distribution of GM atrophy in clinically early primary
      progressive MS (PPMS). DESIGN AND PATIENTS: Thirty-one patients with PPMS within
      5 years of symptom onset (mean age, 43.2 years; median Expanded Disability Status
      Scale score, 4.5) and 15 healthy control subjects (mean age, 43.7 years) were
      studied. All subjects underwent a 3-dimensional inversion-recovery fast spoiled
      gradient-recalled echo sequence that was repeated after 1 year in patients only.
      Magnetic resonance images underwent an optimized voxel-based morphometric
      analysis that segments magnetic resonance data volumes in a normalized space and
      quantifies tissue atrophy on a voxel-by-voxel basis. A lesion mask was created
      for each patient and used in normalization and segmentation steps to minimize
      bias from lesions. A multisubject design was used in the cross-sectional study to
      compare patients with PPMS and controls. A 1-way analysis of variance (within
      subjects) design was used in the longitudinal study. RESULTS: At baseline,
      patients with PPMS displayed bilateral thalamic atrophy compared with controls.
      In addition, a significant association between lesion load and decreased GM
      volume was found for the thalami. Loss of GM in the putamen, caudate, thalami,
      and cortical and infratentorial areas was observed in patients after 1 year of
      follow-up. CONCLUSIONS: Atrophy is most obvious in deep GM in clinically early
      PPMS. This may reflect increased sensitivity of these regions to
      neurodegeneration. Cortical and infratentorial atrophy developed as the disease
      evolved.

PMID- 16908749
TI  - Deep brain stimulation of the internal segment of the globus pallidus in delayed
      runaway dyskinesia.
AB  - BACKGROUND: Dyskinesias that occur during a period without medication after
      embryonic cell transplantation have been commonly reported in double-blind
      trials; however, to date, they have not been reported in the few patients who
      participated in open-label pilot studies. DESIGN: Single case observation with
      preoperative and postoperative data, and intraoperative single-cell physiology.
      PATIENT: A patient who underwent embryonic cell transplantation in 1993 as part
      of the University of South Florida open-label study was referred for evaluation
      of intractable dyskinesia of the right arm. The dyskinesia was present during
      evaluation of the patient after a 12-hour period without medication and was
      clinically disabling. It was manifested as a severe groping movement of the hand.
      Intraoperative physiologic evaluation revealed decreased firing rates in the
      internal segment of the globus pallidus. RESULTS: Deep brain stimulation of the
      internal segment of the globus pallidus resulted in resolution of the dyskinesia.
      CONCLUSION: This case highlights the delayed development of runaway dyskinesia
      after a period without medication as an important potential long-term adverse
      effect of embryonic cell transplantation in patients with Parkinson disease.

PMID- 16908750
TI  - Broadening the phenotype of childhood-onset dopa-responsive dystonia.
AB  - BACKGROUND: Dopa-responsive dystonia (DRD) may cause early-onset dystonia, with
      extrapyramidal or pyramidal tract dysfunction. OBJECTIVE: To broaden the
      phenotype of DRD. SETTING: Tertiary referral university hospital. PATIENTS: We
      describe 4 female siblings with genetically confirmed DRD, 3 of whom presented
      with "unsteadiness" and 1 with scoliosis. All had dystonia and pyramidal tract
      signs, 3 had additional extrapyramidal features (resting tremor, bradykinesia, or
      rigidity), and at least 2 had definite signs of cerebellar dysfunction. MAIN
      OUTCOME MEASURES: The subjective response to treatment with 62.5 mg of a
      combination product of levodopa and carbidopa 3 times daily was assessed at both
      6- and 12-month follow-up visits with the 7-item Patient's Global Impression of
      Change Scale as very much improved, much improved, a little improved, no
      different, a little worse, much worse, or very much worse. RESULTS: All patients
      showed a good response to levodopa therapy 41 to 49 years after symptom onset.
      CONCLUSION: Cerebellar signs may be observed in patients with DRD and may improve
      in response to levodopa.

PMID- 16908751
TI  - Essential tremor associated with pathologic changes in the cerebellum.
AB  - BACKGROUND: Although essential tremor (ET) is one of the most common neurologic
      disorders, there have been few postmortem studies. We recently reported
      postmortem changes (torpedoes and Bergmann gliosis) in the cerebellar cortex in a
      few ET cases. OBJECTIVE: To describe more extensive postmortem changes in the
      cerebellum in another ET case. DESIGN: Case report. RESULTS: A 90-year-old woman
      had a 30-year history of ET. At postmortem examination, there was segmental loss
      of Purkinje cells, presence of torpedoes, and Bergmann gliosis in the cerebellar
      cortex. Moreover, there were extensive changes in the dentate nucleus, in the
      form of neuronal loss, neuronal atrophy, microglial clusters, and reduction in
      the number of efferent fibers (ie, pallor of the hilum). CONCLUSIONS: The brain
      in the current case exhibited more marked cerebellar pathologic features than
      noted in previously reported ET cases and thereby extends the described
      cerebellar findings in this common, yet pathologically poorly characterized,
      neurologic disorder.

PMID- 16908752
TI  - A novel mitochondrial transfer RNA(Asn) mutation causing multiorgan failure.
AB  - BACKGROUND: Mitochondrial cytopathies are a heterogeneous group of disorders with
      a broad spectrum of clinical symptoms. OBJECTIVE: To characterize a novel
      mutation in the transfer RNA(Asn) (m.5728A>G) identified in a 13-year-old boy
      with multiorgan failure. DESIGN: Biochemical and immunocytochemical studies were
      performed in combination with transmitochondrial cybrid analysis. SETTING: A
      university hospital. Molecular and biochemical analyses were performed in
      collaboration between 2 other university hospitals. PATIENT: Thirteen-year-old
      boy with multiorgan failure. RESULTS: In the patient's muscle tissue and cultured
      skin fibroblasts, a combined deficiency of complexes I and IV was found, using
      spectrophotometric analysis and activity staining in the gel following blue
      native polyacrylamide gel electrophoresis. An identical biochemical profile was
      seen in transmitochondrial cybrids carrying more than 55% mutant mitochondrial
      DNA. CONCLUSION: These data suggest that the m.5728A>G transition is a pathogenic
      mutation and is the cause of the respiratory chain dysfunction in the propositus.

PMID- 16908753
TI  - Late-onset mitochondrial myopathy, encephalopathy, lactic acidosis, and
      strokelike episodes with bitemporal lesions.

PMID- 16908754
TI  - Hippocampal involvement in valproate-induced acute hyperammonemic encephalopathy.

PMID- 16908755
TI  - Primary vs postparalytic hemifacial spasm.

PMID- 16908756
TI  - Compliance with hypertensive therapy.

PMID- 16908757
TI  - Enalapril attenuates downregulation of Angiotensin-converting enzyme 2 in the
      late phase of ventricular dysfunction in myocardial infarcted rat.
AB  - The early and long-term effects of coronary artery ligation on the plasma and
      left ventricular angiotensin-converting enzyme (ACE and ACE2) activities, ACE and
      ACE2 mRNA levels, circulating angiotensin (Ang) levels [Ang I, Ang-(1-7), Ang-(1
      9), and Ang II], and cardiac function were evaluated 1 and 8 weeks after
      experimental myocardial infarction in adult Sprague Dawley rats. Sham-operated
      rats were used as controls. Coronary artery ligation caused myocardial
      infarction, hypertrophy, and dysfunction 8 weeks after surgery. At week 1,
      circulating Ang II and Ang-(1-9) levels as well as left ventricular and plasma
      ACE and ACE2 activities increased in myocardial-infarcted rats as compared with
      controls. At 8 weeks post-myocardial infarction, circulating ACE activity, ACE
      mRNA levels, and Ang II levels remained higher, but plasma and left ventricular
      ACE2 activities and mRNA levels and circulating levels of Ang-(1-9) were lower
      than in controls. No changes in plasma Ang-(1-7) levels were observed at any
      time. Enalapril prevented cardiac hypertrophy and dysfunction as well as the
      changes in left ventricular ACE, left ventricular and plasmatic ACE2, and
      circulating levels of Ang II and Ang-(1-9) after 8 weeks postinfarction. Thus,
      the decrease in ACE2 expression and activity and circulating Ang-(1-9) levels in
      late ventricular dysfunction post-myocardial infarction were prevented with
      enalapril. These findings suggest that in this second arm of the renin
      angiotensin system, ACE2 may act through Ang-(1-9), rather than Ang-(1-7), as a
      counterregulator of the first arm, where ACE catalyzes the formation of Ang II.

PMID- 16908758
TI  - Acute reduction of blood pressure by nitroglycerin does not normalize large
      artery stiffness in essential hypertension.
AB  - Stiffness of large elastic arteries is elevated in subjects with hypertension, an
      effect that could potentially be explained by increased distending pressure. We
      examined effects of an acute change in blood pressure on carotid-femoral pulse
      wave velocity and carotid artery distensibility (inversely related to stiffness)
      in normotensive control subjects (n=20, mean age 42) with mean arterial pressure
      (MAP) 84+/-1.7 mm Hg (mean+/-SE) and subjects with essential hypertension (n=20,
      mean age 45, MAP 104+/-2.0 mm Hg). Normotensive subjects received intravenous
      nitroglycerin (NTG) and angiotensin II to lower/increase blood pressure.
      Hypertensive subjects received NTG to lower blood pressure. Pulse wave velocity
      was 24% (95% CI: 12% to 35%) higher and carotid distensibility 47% (95% CI: 32%
      to 63%) lower in hypertensive subjects compared with controls. In normotensive
      subjects, acute changes in blood pressure produced expected changes in stiffness.
      However, in hypertensive subjects, despite reducing MAP by 22 mm Hg to the same
      level as in normotensive subjects, there was no detectable reduction in arterial
      stiffness: pulse wave velocity remained 24% (95% CI: 10% to 38%) higher and
      carotid distensibility 48% (95% CI: 31% to 63%) lower in hypertensive compared
      with normotensive subjects. Because blood pressure-independent effects of NTG
      are, if anything, to reduce stiffness, these results indicate that elevated
      carotid and aortic stiffness in hypertensive subjects is not explained by
      elevated blood pressure but relates to structural change in the arterial wall.

PMID- 16908759
TI  - Arterial blood pressure and stiffness in hypertension: is arterial structure
      important?

PMID- 16908760
TI  - Risk of thromboembolic events after percutaneous left atrial radiofrequency
      ablation of atrial fibrillation.
AB  - BACKGROUND: In patients with atrial fibrillation (AF), the risk of thromboembolic
      events (TEs) is variable and is influenced by the presence and number of comorbid
      conditions. The effect of percutaneous left atrial radiofrequency ablation
      (LARFA) of AF on the risk of TEs is unclear. METHODS AND RESULTS: LARFA was
      performed in 755 consecutive patients with paroxysmal (n = 490) or chronic (n =
      265) AF. Four hundred eleven patients (56%) had > or = 1 risk factor for stroke.
      All patients were anticoagulated with warfarin for > or = 3 months after LARFA. A
      TE occurred in 7 patients (0.9%) within 2 weeks of LARFA. A late TE occurred 6 to
      10 months after ablation in 2 patients (0.2%), 1 of whom still had AF, despite
      therapeutic anticoagulation in both. Among 522 patients who remained in sinus
      rhythm after LARFA, warfarin was discontinued in 79% of 256 patients without risk
      factors and in 68% of 266 patients with > or = 1 risk factor. Patients older than
      65 years or with a history of stroke were more likely to remain anticoagulated
      despite a successful outcome from LARFA. None of the patients in whom
      anticoagulation was discontinued had a TE during 25 +/- 8 months of follow-up.
      CONCLUSIONS: The risk of a TE after LARFA is 1.1%, with most events occurring
      within 2 weeks after the procedure. Discontinuation of anticoagulant therapy
      appears to be safe after successful LARFA, both in patients without risk factors
      for stroke and in patients with risk factors other than age > 65 years and
      history of stroke. Sufficient safety data are as yet unavailable to support
      discontinuation of anticoagulation in patients older than 65 years or with a
      history of stroke.

PMID- 16908761
TI  - Risk stratification of patients with acute anterior myocardial infarction and
      right bundle-branch block: importance of QRS duration and early ST-segment
      resolution after fibrinolytic therapy.
AB  - BACKGROUND: Patients with an acute anterior ST-segment elevation myocardial
      infarction and right bundle-branch block (RBBB) have a high mortality risk, which
      may be stratified by early ECG changes. METHODS AND RESULTS: In the Hirulog Early
      Reperfusion Occlusion (HERO-2) trial, 17 073 patients with acute myocardial
      infarction (AMI) within 6 hours of symptom onset were treated with streptokinase
      and randomized to receive bivalirudin or heparin. There was no difference in the
      primary end point of 30-day mortality. ECGs were recorded at randomization and 60
      minutes after fibrinolytic therapy was begun. The 30-day mortality rate was 31.6%
      in the 415 patients with RBBB and anterior AMI at randomization and 33% in the
      100 patients who developed new RBBB at 60 minutes from normal baseline conduction
      accompanying an anterior AMI. An increase in QRS duration by 20-ms increments was
      associated with increasing 30-day mortality rate in both RBBB groups on
      multivariable analyses with covariates of age, Killip class, systolic blood
      pressure, pulse, and prior infarction. Patients with QRS duration > or = 160 ms
      had higher 30-day mortality rate than those with QRS duration < 160 ms (37.2%
      versus 27.2%, P = 0.03, and 46.2% versus 24.5%, P = 0.025, in the 2 groups,
      respectively). For the patients with RBBB and anterior MI at randomization, RBBB
      resolved at 60 minutes in 40 patients, but 30-day mortality rate was unchanged.
      For those with persisting RBBB at 60 minutes, 30-day mortality rate was lower if
      ST-segment elevation had resolved by > or = 50% (20.4% versus 35.3%, P = 0.006).
      CONCLUSIONS: In patients with anterior AMI and RBBB, increasing QRS duration is
      associated with increasing 30-day mortality. Early ST-segment resolution after
      fibrinolytic therapy despite persisting RBBB is associated with lower mortality
      rate.

PMID- 16908762
TI  - Alpha2(VIII) collagen substrata enhance endothelial cell retention under acute
      shear stress flow via an alpha2beta1 integrin-dependent mechanism: an in vitro
      and in vivo study.
AB  - BACKGROUND: Essential to tissue-engineered vascular grafts is the formation of a
      functional endothelial monolayer capable of resisting the forces of blood flow.
      This study targeted alpha2(VIII) collagen, a major component of the
      subendothelial matrix, and examined the ability of and mechanisms by which
      endothelial cells attach to this collagen under static and dynamic conditions
      both in vitro and in vivo. METHODS AND RESULTS: Attachment of human endothelial
      cells to recombinant alpha2(VIII) collagen was assessed in vitro under static and
      shear conditions of up to 100 dyne/cm2. Alpha2(VIII) collagen supported
      endothelial cell attachment in a dose-dependent manner, with an 18-fold higher
      affinity for endothelial cells compared with fibronectin. Cell attachment was
      significantly inhibited by function-blocking anti-alpha2 (56%) and -beta1 (98%)
      integrin antibodies but was not RGD dependent. Under flow, endothelial cells were
      retained at significantly higher levels on alpha2(VIII) collagen (53% and 51%)
      than either fibronectin (23% and 16%) or glass substrata (7% and 1%) at shear
      rates of 30 and 60 dyne/cm2, respectively. In vivo studies, using endothelialized
      polyurethane grafts, demonstrated significantly higher cell retention rates to
      alpha2(VIII) collagen-coated than to fibronectin-coated prostheses in the
      midgraft area (P < 0.05) after 24 hours' implantation in the caprine carotid
      artery. CONCLUSIONS: These studies demonstrate that alpha2(VIII) collagen has the
      potential to improve both initial cell attachment and retention of endothelial
      cells on vascular grafts in vivo, which opens new avenues of research into the
      development of single-stage endothelialized prostheses and the next generation of
      tissue-engineered vascular grafts.

PMID- 16908763
TI  - Augmentation of myocardial production of 15-epi-lipoxin-a4 by pioglitazone and
      atorvastatin in the rat.
AB  - BACKGROUND: Both statins and thiazolidinediones have antiinflammatory properties.
      However, the exact mechanisms underlying these effects are unknown. We
      investigated whether atorvastatin (ATV) and pioglitazone (PIO) increase the
      myocardial content of lipoxin-A4 and 15(R)-epi-lipoxin-A4 (15-epi-LXA4), both
      arachidonic acid products with strong antiinflammatory properties. METHODS AND
      RESULTS: In experiment 1, rats received 3-day pretreatment with water; PIO 2, 5,
      or 10 mg x kg(-1) x d(-1); ATV 2, 5, or 10 mg x kg(-1) x d(-1); or PIO 10 mg x
      kg(-1) x d(-1)+ATV 10 mg x kg(-1) x d(-1). In experiment 2, rats received water;
      PIO 10 mg x kg(-1) x d(-1)+ATV 10 mg x kg(-1) x d(-1); PIO+ATV and valdecoxib, a
      selective cyclooxygenase-2 (COX-2) inhibitor; PIO+ATV and zileuton, a selective 5
      lipoxygenase inhibitor; or zileuton alone. There were 4 rats in each group.
      Hearts were harvested and analyzed for myocardial lipoxin-A4 and 15-epi-LXA4
      levels and for COX-2 and 5-lipoxygenase protein expression. ATV and PIO at 5 and
      10 mg x kg(-1) . d(-1) significantly increased myocardial 15-epi-LXA4 levels
      compared with the sham-treated group (0.51 +/- 0.02 ng/mg). Myocardial 15-epi
      LXA4 were significantly higher in the PIO+ATV group (1.29 +/- 0.02 ng/mg; P <
      0.001 versus each other group). Both valdecoxib and zileuton abrogated the
      PIO+ATV increase in 15-epi-LXA4, whereas zileuton alone had no effect. PIO, ATV,
      and their combination resulted in a small increase in myocardial lipoxin-A4
      levels, which was not statistically significant. ATV alone or in combination with
      PIO markedly augmented COX-2 expression. PIO had a much smaller effect on COX-2
      expression. Myocardial expression of 5-lipoxygenase was not altered by PIO, ATV,
      or their combination. CONCLUSIONS: Both PIO and ATV increase myocardial levels of
      15-epi-LXA4, a mediator with antiinflammatory properties. This finding may
      explain the antiinflammatory properties of both PIO and ATV.

PMID- 16908764
TI  - Redefinition of myocardial infarction: prospective evaluation in the community.
AB  - BACKGROUND: The 2000 European Society of Cardiology/American College of
      Cardiology definition for myocardial infarction (MI) combines ischemic symptoms,
      electrocardiographic changes, and troponin rather than creatine kinase levels.
      The use of troponins will increase the detection of MI by a magnitude to be
      quantified, and the clinical acceptance of the new definition is unknown. METHOD
      AND RESULTS: Subjects presenting to an Olmsted County facility with a troponin T
      value > or = 0.03 ng/mL between November 2002 and March 2005 were prospectively
      classified through the use of standardized MI criteria, relying on cardiac pain,
      Minnesota coding of the ECG, and troponin, creatine kinase, and its MB fraction
      measured simultaneously. Through the use of dynamic changes in troponin, 538 MIs
      were identified versus 327 with creatine kinase and 427 with only the MB fraction
      of creatine kinase. This represents a 74% (95% confidence interval [CI], 69% to
      79%) increase above the number of MIs identified with creatine kinase and a 41%
      (95% CI, 37% to 46%) increase above the number identified with criteria including
      only its MB fraction. When relying on single values of troponin, increases in the
      number of MIs were always large but varied widely according to the threshold used
      for troponin. Cases meeting only troponin-based criteria were less likely to have
      electrocardiographic ST-segment elevation and had better survival than those
      identified with previous criteria. Clinician diagnoses mentioned MI in 42% (95%
      CI, 34% to 49%) of cases meeting only troponin-based criteria versus 74% (95% CI,
      69% to 78%) for MIs meeting the previous criteria (P < 0.001). CONCLUSIONS: The
      prospective application of the new criteria in the community results in a large
      increase in the number of MIs and a change in case mix. The clinical acceptance
      of the new criteria is incomplete, and studies that rely exclusively on dismissal
      diagnoses to assess MI rates may underestimate the burden of disease as presently
      defined.

PMID- 16908765
TI  - Angiotensin II induces premature senescence of vascular smooth muscle cells and
      accelerates the development of atherosclerosis via a p21-dependent pathway.
AB  - BACKGROUND: Angiotensin II (Ang II) has been reported to contribute to the
      pathogenesis of various human diseases including atherosclerosis, and inhibition
      of Ang II activity has been shown to reduce the morbidity and mortality of
      cardiovascular diseases. We have previously demonstrated that vascular cell
      senescence contributes to the pathogenesis of atherosclerosis; however, the
      effects of Ang II on vascular cell senescence have not been examined. METHODS AND
      RESULTS: Ang II significantly induced premature senescence of human vascular
      smooth muscle cells (VSMCs) via the p53/p21-dependent pathway in vitro.
      Inhibition of this pathway effectively suppressed induction of proinflammatory
      cytokines and premature senescence of VSMCs by Ang II. Ang II also significantly
      increased the number of senescent VSMCs and induced the expression of
      proinflammatory molecules and of p21 in a mouse model of atherosclerosis. Loss of
      p21 markedly ameliorated the induction of proinflammatory molecules by Ang II,
      thereby preventing the development of atherosclerosis. Replacement of p21
      deficient bone marrow cells with wild-type cells had little influence on the
      protective effect of p21 deficiency against the progression of atherogenesis
      induced by Ang II. CONCLUSIONS: We demonstrated that Ang II promotes vascular
      inflammation by inducing premature senescence of VSMCs both in vitro and in vivo.
      Our results suggest a critical role of p21-dependent premature senescence of
      VSMCs in the pathogenesis of atherosclerosis.

PMID- 16908766
TI  - Clinical phenotype and functional characterization of CASQ2 mutations associated
      with catecholaminergic polymorphic ventricular tachycardia.
AB  - BACKGROUND: Four distinct mutations in the human cardiac calsequestrin gene
      (CASQ2) have been linked to catecholaminergic polymorphic ventricular tachycardia
      (CPVT). The mechanisms leading to the clinical phenotype are still poorly
      understood because only 1 CASQ2 mutation has been characterized in vitro. METHODS
      AND RESULTS: We identified a homozygous 16-bp deletion at position 339 to 354
      leading to a frame shift and a stop codon after 5aa (CASQ2(G112+5X)) in a child
      with stress-induced ventricular tachycardia and cardiac arrest. The same deletion
      was also identified in association with a novel point mutation (CASQ2(L167H)) in
      a highly symptomatic CPVT child who is the first CPVT patient carrier of compound
      heterozygous CASQ2 mutations. We characterized in vitro the properties of CASQ2
      mutants: CASQ2(G112+5X) did not bind Ca2+, whereas CASQ2(L167H) had normal
      calcium-binding properties. When expressed in rat myocytes, both mutants
      decreased the sarcoplasmic reticulum Ca2+-storing capacity and reduced the
      amplitude of I(Ca)-induced Ca2+ transients and of spontaneous Ca2+ sparks in
      permeabilized myocytes. Exposure of myocytes to isoproterenol caused the
      development of delayed afterdepolarizations in CASQ2(G112+5X). CONCLUSIONS:
      CASQ2(L167H) and CASQ2(G112+5X) alter CASQ2 function in cardiac myocytes, which
      leads to reduction of active sarcoplasmic reticulum Ca2+ release and calcium
      content. In addition, CASQ2(G112+5X) displays altered calcium-binding properties
      and leads to delayed afterdepolarizations. We conclude that the 2 CASQ2 mutations
      identified in CPVT create distinct abnormalities that lead to abnormal
      intracellular calcium regulation, thus facilitating the development of
      tachyarrhythmias.

PMID- 16908767
TI  - Skeletonized internal thoracic artery harvest reduces pain and dysesthesia and
      improves sternal perfusion after coronary artery bypass surgery: a randomized,
      double-blind, within-patient comparison.
AB  - BACKGROUND: Observational studies suggest that skeletonization of the internal
      thoracic artery (ITA) can improve conduit flow and length and reduce deep sternal
      infections and postoperative pain. We performed a randomized, double-blind,
      within-patient comparison of skeletonized and nonskeletonized ITAs in patients
      undergoing coronary surgery. METHODS AND RESULTS: Patients (n = 48) undergoing
      bilateral ITA harvest were randomized to receive 1 skeletonized and 1
      nonskeletonized ITA. Intraoperatively, ITA flow was assessed directly and with a
      Doppler flow probe before and after topical application of papaverine. ITA
      harvest time and conduit length were recorded. A blinded assessment of pain
      (visual analog scale) and dysesthesia (physical examination) was performed at
      discharge, at 2 weeks, and at a 3-month follow-up. Sternal perfusion was assessed
      with nuclear imaging (n = 7). Skeletonization required longer ITA harvest times
      (27 +/- 1 versus 24 +/- 1 minutes; P = 0.04). There was a trend toward increased
      ITA length in the skeletonized group (18.2 +/- 0.3 versus 17.7 +/- 0.3 cm; P =
      0.09). In situ ITA flow was lower in skeletonized arteries (7.4 +/- 0.9 versus
      10.1 +/- 1.0 mL/min; P = 0.01) and increased significantly after ITA division and
      papaverine application. Postanastomotic flows were similar between groups.
      Skeletonization was associated with decreased pain at the 3-month follow-up and a
      reduction in major sensory deficits at the 4-week and 3-month (17% versus 50%; P
      = 0.002) follow-ups. Baseline adjusted sternal perfusion was significantly
      greater by 17 +/- 6% (P = 0.03) on the skeletonized side. CONCLUSIONS:
      Skeletonization results in reduced postoperative pain and dysesthesia and
      increased sternal perfusion at follow-up but does not produce increased conduit
      flow. ITA skeletonization may be a strategy for reducing morbidity after CABG.

PMID- 16908768
TI  - Primary Stenting of Totally Occluded Native Coronary Arteries II (PRISON II): a
      randomized comparison of bare metal stent implantation with sirolimus-eluting
      stent implantation for the treatment of total coronary occlusions.
AB  - BACKGROUND: Sirolimus-eluting stents markedly reduce the risk of restenosis
      compared with bare metal stents. However, it is not known whether there are
      differences in effectiveness between bare metal and sirolimus-eluting stents in
      patients with total coronary occlusions. METHODS AND RESULTS: In a prospective,
      randomized, single-blind, 2-center trial, we enrolled 200 patients with total
      coronary occlusions: Half (n = 100) were randomly assigned to receive bare metal
      BxVelocity stents and half (n = 100) to receive sirolimus-eluting Cypher stents.
      The primary end point was angiographic binary in-segment restenosis rate at 6
      month follow-up. Secondary end points were a composite of major adverse cardiac
      events, target vessel failure, binary in-stent restenosis rate, in-stent and in
      segment minimal lumen diameter, percent diameter stenosis, and late luminal loss
      at 6-month follow-up. The sirolimus stent group showed a significantly lower in
      stent binary restenosis rate of 7% compared with 36% in the bare metal stent
      group (P < 0.001). The in-segment binary restenosis rate was 11% in the group
      receiving a sirolimus stent versus 41% in the bare metal stent group (P <
      0.0001), resulting in a target lesion revascularization rate of 4% in the
      sirolimus group versus 19% in the bare metal group (P < 0.001). Patients who
      received the drug-eluting stent also had significantly lower rates of target
      vessel revascularization, target vessel failure, and all major adverse cardiac
      events. CONCLUSIONS: In patients with total coronary occlusions, use of the
      sirolimus-eluting stents are superior to the bare metal stents with significant
      reduction in angiographic binary restenosis, resulting in significantly less need
      for target lesion and target vessel revascularization.

PMID- 16908769
TI  - Adverse impact of bleeding on prognosis in patients with acute coronary
      syndromes.
AB  - BACKGROUND: The use of multiple antithrombotic drugs and aggressive invasive
      strategies has increased the risk of major bleeding in acute coronary syndrome
      (ACS) patients. It is not known to what extent bleeding determines clinical
      outcome. METHODS AND RESULTS: Using Cox proportional-hazards modeling, we
      examined the association between bleeding and death or ischemic events in 34,146
      patients with ACS enrolled in the Organization to Assess Ischemic Syndromes and
      the Clopidogrel in Unstable Angina to Prevent Recurrent Events studies. Patients
      with major bleeding were older, more often had diabetes or a history of stroke,
      had a lower blood pressure and higher serum creatinine, more often had ST-segment
      changes on the presenting ECG, and had a 5-fold-higher incidence of death during
      the first 30 days (12.8% versus 2.5%; P < 0.0001) and a 1.5-fold-higher incidence
      of death between 30 days and 6 months (4.6% versus 2.9%; P = 0.002). Major
      bleeding was independently associated with an increased hazard of death during
      the first 30 days (hazard ratio, 5.37; 95% CI, 3.97 to 7.26; P < 0.0001), but the
      hazard was much weaker after 30 days (hazard ratio, 1.54; 95% CI, 1.01 to 2.36; P
      = 0.047). The association was consistent across subgroups according to
      cointerventions during hospitalization, and there was an increasing risk of death
      with increasing severity of bleeding (minor less than major less than life
      threatening; P for trend = 0.0009). A similar association was evident between
      major bleeding and ischemic events, including myocardial infarction and stroke.
      CONCLUSIONS: In ACS patients without persistent ST-segment elevation, there is a
      strong, consistent, temporal, and dose-related association between bleeding and
      death. These data should lead to greater awareness of the prognostic importance
      of bleeding in ACS and should prompt evaluation of strategies to reduce bleeding
      and thereby improve clinical outcomes.

PMID- 16908770
TI  - Promoting physical activity in children and youth: a leadership role for schools:
      a scientific statement from the American Heart Association Council on Nutrition,
      Physical Activity, and Metabolism (Physical Activity Committee) in collaboration
      with the Councils on Cardiovascular Disease in the Young and Cardiovascular
      Nursing.

PMID- 16908771
TI  - Beta2-Adrenergic agonists suppress rat autoimmune myocarditis: potential role of
      beta2-adrenergic stimulants as new therapeutic agents for myocarditis.
AB  - BACKGROUND: The therapeutic potential of beta2-adrenergic receptor (AR) agonists
      in the treatment of autoimmune diseases has been reported. However, the role of
      these drugs in the myocardial structure-induced autoimmune process, which is
      thought to play a crucial role in the progression of myocarditis to subsequent
      complications, has not been elucidated. METHODS AND RESULTS: Experimental
      autoimmune myocarditis (EAM) was induced in rats by immunization with cardiac
      myosin. On daily administration from day 0 after immunization, the beta2
      selective AR agonists formoterol or salbutamol ameliorated EAM on day 21 and
      increased myocardial interleukin-10/interferon-gamma mRNA levels. Propranolol, a
      nonselective beta-AR antagonist, aggravated EAM on day 21 and decreased mRNA
      levels, whereas metoprolol, a beta1-selective AR antagonist, showed no effect.
      These results were reflected in vivo by the proliferation of cardiac myosin
      primed lymph node cells from drug-treated rats. In vitro addition of beta2
      selective AR agonists inhibited the activation of cardiac myosin fragment
      specific myocarditogenic T lymphocytes, and this effect was reversed by
      ICI118,551, a beta2-selective AR antagonist. Furthermore, treatment with 2
      different beta2-selective AR agonists starting on day 14 also ameliorated EAM on
      day 21. CONCLUSIONS: beta2-AR stimulation suppressed the development of EAM by
      inhibiting cardiac myosin-specific T-lymphocyte activation in lymphoid organs and
      by shifting the imbalance in Th1/Th2 cytokine toward Th2 cytokine. Furthermore,
      it also ameliorated established myocardial inflammation. beta2-AR-stimulating
      agents may represent important immunomodulators of the cardiac myosin-induced
      autoimmune process and have potential as a new therapy for myocarditis.

PMID- 16908772
TI  - Oxidized lipid-driven chemokine receptor switch, CCR2 to CX3CR1, mediates
      adhesion of human macrophages to coronary artery smooth muscle cells through a
      peroxisome proliferator-activated receptor gamma-dependent pathway.
AB  - BACKGROUND: Recent genetic data in mouse and humans suggest that the chemokine
      receptors CCR2 and CX3CR1 are involved in atherogenesis; however, detailed
      molecular and cellular mechanisms have not been fully delineated. METHODS AND
      RESULTS: Here, we show that oxidized linoleic acid metabolites, which are
      components of oxidized LDL found in large amounts in atherosclerotic plaque, were
      able to specifically induce differentiation of human monocytes to macrophages
      with decreased expression of CCR2, confirming a previous report, and increased
      expression of CX3CR1. These macrophages acquired the ability to adhere to
      coronary artery smooth muscle cells. The adhesion was mediated directly and
      predominantly by CX3CR1. Reciprocal effects of these lipids on CCR2 and CX3CR1
      expression were mediated by the nuclear receptor peroxisome proliferator
      activated receptor (PPAR) gamma, and targeting the PPARgamma gene with sRNAi
      dramatically reduced macrophage adhesion to coronary artery smooth muscle cells.
      CONCLUSIONS: These data suggest that in atherogenesis oxidized lipid-driven
      activation of macrophage PPARgamma in the intima may result in a proadhesive
      chemokine receptor switch-CCR2 off, CX3CR1 on-causing cessation of CCR2-dependent
      migration and activation of CX3CR1-dependent retention mechanisms, which together
      promote macrophage accumulation in vessel wall. Our results may explain at the
      molecular and cell biology levels the genetic link between CX3CR1 and
      atherosclerosis. Moreover, they identify macrophage binding to coronary artery
      smooth muscle cells as the first primary cell setting in which CX3CR1 functions
      as the major adhesion system.

PMID- 16908773
TI  - Randomized, double-blind, multicenter study of the Endeavor zotarolimus-eluting
      phosphorylcholine-encapsulated stent for treatment of native coronary artery
      lesions: clinical and angiographic results of the ENDEAVOR II trial.
AB  - BACKGROUND: The use of the Endeavor stent might reduce restenosis and stent
      thrombosis at 9 months. METHODS AND RESULTS: Patients (n = 1197) treated for
      single coronary artery stenosis were enrolled in a prospective, randomized,
      double-blind study and randomly assigned to receive the Endeavor zotarolimus
      eluting phosphorylcholine polymer-coated stent (n = 598) or the same bare metal
      stent but without the drug or the polymer coating (n = 599). The 2 groups were
      well matched in baseline characteristics. Diabetes was present in 20.1% of
      patients; the mean reference vessel diameter was 2.75 mm; and the mean lesion
      length was 14.2 mm. The primary end point of target vessel failure at 9 months
      was reduced from 15.1% with the bare metal stent to 7.9% with the Endeavor (P =
      0.0001), and the rate of major adverse cardiac events was reduced from 14.4% with
      the bare metal stent to 7.3% with the Endeavor (P = 0.0001). Target lesion
      revascularization was 4.6% with Endeavor compared with 11.8% with the bare metal
      stent (P = 0.0001). The rate of stent thrombosis was 0.5% with the Endeavor,
      which was not significantly different from 1.2% with the bare metal stent. In 531
      patients submitted to angiographic follow-up, late loss was reduced from 1.03 +/-
      0.58 to 0.61 +/- 0.46 (P < 0.001) in stent and from 0.72 +/- 0.61 to 0.36 +/-
      0.46 (P < 0.001) in segment. The rate of in-segment restenosis was reduced from
      35.0% to 13.2% with Endeavor (P < 0.0001). There was no excessive edge stenosis,
      aneurysm formation, or late acquired malapposition by intravascular ultrasound
      imaging. Differences in clinical outcome were maintained at 12 and 24 months (P <
      0.0001). CONCLUSIONS: Compared with bare metal stents, the Endeavor stent is safe
      and reduces the rates of clinical and angiographic restenosis at 9, 12, and 24
      months.

PMID- 16908774
TI  - Endogenous endothelin-1 is required for cardiomyocyte survival in vivo.
AB  - BACKGROUND: Endothelin-1 (ET-1) has potent vasoconstrictor and hypertrophic
      actions. Pharmacological antagonists of endothelin receptors attenuate cardiac
      hypertrophy, have been approved for treatment of pulmonary hypertension, and are
      under investigation for treatment of heart failure. To investigate the role of ET
      1 in the heart, we created mice with cardiomyocyte deletion of ET-1. METHODS AND
      RESULTS: Mice with cardiomyocyte-specific deletion of ET-1 are phenotypically
      normal when young. Remarkably, as the mice age or when young animals are
      subjected to aortic banding, they develop an unexpected phenotype of progressive
      systolic dysfunction and cardiac dilation. Echocardiography, necropsy, histology,
      and molecular phenotype confirm a dilated cardiomyopathy. Terminal
      deoxynucleotidyl transferase-mediated dUTP nick-end-labeling analysis reveals
      greater abundance of apoptotic nuclei in the ET-1-deficient hearts.
      Transcriptional and Western analyses suggest enhanced tumor necrosis factor (TNF)
      mediated apoptosis with increases in caspase-8 activity. These ET-1-deficient
      hearts also have diminished nuclear factor (NF)-kappaB activity, resulting in
      diminution of downstream inhibitors of TNF signaling. CONCLUSIONS: Local ET-1
      gene expression is necessary to maintain normal cardiac function and
      cardiomyocyte survival in mice with both age and hemodynamic stress. This cardiac
      protective effect is mediated by paracrine ET-1 modulation of TNF-related
      apoptosis, in part through upregulation of NF-kappaB signaling.

PMID- 16908775
TI  - Carotid artery disease.

PMID- 16908776
TI  - Images in cardiovascular medicine. A rare form of midventricular Tako-Tsubo after
      emotional stress followed up with magnetic resonance imaging.

PMID- 16908777
TI  - Images in cardiovascular medicine. Spontaneous left atrial dissection and
      hematoma mimicking a cardiac tumor: findings from echocardiography, cardiac
      computed tomography, magnetic resonance imaging, and pathology.

PMID- 16908778
TI  - Images in cardiovascular medicine. Wall motion abnormalities detection with
      contrast-enhanced multislice computed tomography.

PMID- 16908779
TI  - Letter by Bourque et al regarding article, "Changing incidence and survival for
      heart failure in a well-defined older population, 1970-1974 and 1990-1994".

PMID- 16908780
TI  - Letter by Timpson et al regarding article, "Contribution of clinical correlates
      and 13 C-reactive protein gene polymorphisms to interindividual variability in
      serum C-reactive protein level".

PMID- 16908781
TI  - ACC/AHA/ESC 2006 Guidelines for the Management of Patients with Atrial
      Fibrillation: a report of the American College of Cardiology/American Heart
      Association Task Force on Practice Guidelines and the European Society of
      Cardiology Committee for Practice Guidelines (Writing Committee to Revise the
      2001 Guidelines for the Management of Patients With Atrial Fibrillation):
      developed in collaboration with the European Heart Rhythm Association and the
      Heart Rhythm Society.

PMID- 16908783
TI  - Multislice computed tomography after left main drug-eluting stenting: are we
      putting the cart before the horse?

PMID- 16908784
TI  - Below radar: contributions of cardiac magnetic resonance to the understanding of
      myonecrosis after percutaneous coronary intervention.

PMID- 16908785
TI  - Peripheral arterial disease: morbidity and mortality implications.

PMID- 16908786
TI  - New weapon to curb smoking: no more excuses to delay treatment.

PMID- 16908787
TI  - Cytisine for smoking cessation: a literature review and a meta-analysis.
AB  - BACKGROUND: Cytisine is an agonist of nicotinic receptors; in particular, it
      binds strongly with alpha(4)beta(2) nicotinic receptors. Cytisine has been used
      to treat tobacco dependence for 40 years in Eastern Europe. The objective of this
      study was to review the literature on the effect of cytisine on smoking
      cessation. METHODS: Review of PubMed, EMBASE, Psychological Abstracts, BIOSIS,
      Google.com, and Scholar.google.com, using the keywords cytisine, cytisin,
      zytisin, cytisinum, Tabex, and smoking cessation. Experts and the manufacturer of
      Tabex were contacted. Placebo-controlled trials were included in a meta-analysis.
      RESULTS: Ten studies reported the effects of cytisine on smoking cessation,
      including 4 controlled studies (3 placebo controlled). Nine studies used the
      Bulgarian drug Tabex, containing 1.5 mg of cytisine per tablet, and one Russian
      study used buccal films containing either 1.5 mg of cytisine or 0.75 mg of
      cytisine plus 0.75 mg of anabasine. All studies were published between 1967 and
      2005 in Bulgaria, Germany, Poland, and Russia. There were 4404 smokers treated
      with cytisine and 3518 in control conditions. The pooled odds ratio after 3 to 8
      weeks in the 3 placebo-controlled trials (2 were double blind and 1 was
      randomized) was 1.93 (95% confidence interval, 1.21-3.06). For the 2 placebo
      controlled double-blind trials with a longer follow-up, the pooled odds ratio
      after 3 to 6 months was 1.83 (95% confidence interval, 1.12-2.99). One placebo
      controlled double-blind trial had follow-up after 2 years (odds ratio, 1.77; 95%
      confidence interval, 1.29-2.43). Some adverse effects were reported. Most trials
      were, however, of poor quality. CONCLUSIONS: Cytisine may be effective for
      smoking cessation. This fact remained largely unnoticed in the English-language
      literature.

PMID- 16908788
TI  - Smoking cessation with varenicline, a selective alpha4beta2 nicotinic receptor
      partial agonist: results from a 7-week, randomized, placebo- and bupropion
      controlled trial with 1-year follow-up.
AB  - BACKGROUND: Currently available smoking cessation therapies have limited success
      rates. Varenicline tartrate is a novel, selective nicotinic receptor partial
      agonist developed specifically for smoking cessation. This study evaluated the
      efficacy, tolerability, and safety of 3 varenicline doses for smoking cessation.
      Bupropion hydrochloride was included as an active control. METHODS: A phase 2,
      multicenter, randomized, double-blind, placebo-controlled study of healthy
      smokers (18-65 years old). Subjects were randomized to varenicline tartrate, 0.3
      mg once daily (n = 128), 1.0 mg once daily (n = 128), or 1.0 mg twice daily (n =
      127), for 6 weeks plus placebo for 1 week; to 150-mg sustained-release bupropion
      hydrochloride twice daily (n = 128) for 7 weeks; or to placebo (n = 127) for 7
      weeks. RESULTS: During the treatment phase, the continuous quit rates for any 4
      weeks were significantly higher for varenicline tartrate, 1.0 mg twice daily
      (48.0%; P<.001) and 1.0 mg once daily (37.3%; P<.001), than for placebo (17.1%).
      The bupropion rate was 33.3% (P = .002 vs placebo). The carbon monoxide-confirmed
      continuous quit rates from week 4 to week 52 were significantly higher in the
      varenicline tartrate, 1.0 mg twice daily, group compared with the placebo group
      (14.4% vs 4.9%; P = .002). The bupropion rate was 6.3% (P = .60 vs placebo).
      Discontinuation owing to treatment-emergent adverse events was 15.9% for
      bupropion, 11.2% to 14.3% for varenicline, and 9.8% for placebo. No dose-related
      increases occurred in adverse events for varenicline. CONCLUSIONS: Varenicline
      tartrate demonstrated both short-term (1 mg twice daily and 1 mg once daily) and
      long-term efficacy (1 mg twice daily) vs placebo. Varenicline was well tolerated
      and may provide a novel therapy to aid smoking cessation.

PMID- 16908789
TI  - Efficacy and safety of the novel selective nicotinic acetylcholine receptor
      partial agonist, varenicline, for smoking cessation.
AB  - BACKGROUND: The selective nicotinic acetylcholine receptor partial agonist,
      varenicline tartrate, represents a novel type of therapy for smoking cessation.
      This study evaluated the efficacy, safety, and tolerability of 4 varenicline dose
      regimens, 2 with progressive dosing over the first week (eg, titrated) and 2 with
      a fixed dosing schedule (eg, non-titrated), for promoting smoking cessation.
      METHODS: This multicenter, double-blind, placebo-controlled study randomized
      healthy smokers (aged 18-65 years) to varenicline tartrate, 0.5 mg twice daily
      nontitrated (n = 129), 0.5 mg twice daily titrated (n = 130), 1.0 mg twice daily
      nontitrated (n = 129), 1.0 mg twice daily titrated (n = 130), or placebo (n =
      129) for 12 weeks to aid in smoking cessation. A 40-week follow-up period
      assessed long-term efficacy. The primary efficacy measures were the carbon
      monoxide-confirmed 4-week continuous quit rates by pooled dosage group for weeks
      4 through 7 and 9 through 12 and the continuous abstinence rates for weeks 9
      through 52. RESULTS: Weeks 9 through 12 continuous quit rates were greater in the
      1.0-mg group (49.4%) and the 0.5-mg group (44.0%) vs placebo (11.6%; P<.001 vs
      both doses). Weeks 9 through 52 abstinence rates were greater in the 1.0-mg group
      (22.4%; P<.001) and the 0.5-mg group (18.5%; P<.001) vs placebo (3.9%).
      Varenicline was generally well tolerated, with nausea occurring in 16% to 42% of
      varenicline-treated subjects. Reports of nausea were lower for the titrated vs
      nontitrated dosing and infrequently led to medication discontinuation.
      CONCLUSION: Varenicline tartrate, 0.5 mg and 1.0 mg twice daily, is efficacious
      for smoking cessation.

PMID- 16908791
TI  - Choosing your words carefully: how physicians would disclose harmful medical
      errors to patients.
AB  - BACKGROUND: A gap exists between patients' desire to be told about medical errors
      and present practice. Little is known about how physicians approach disclosure.
      The objective of the present study was to describe how physicians disclose errors
      to patients. METHODS: Mailed survey of 2637 medical and surgical physicians in
      the United States (Missouri and Washington) and Canada (national sample).
      Participants received 1 of 4 scenarios depicting serious errors that varied by
      specialty (medical and surgical scenarios) and by how obvious the error would be
      to the patient if not disclosed (more apparent vs less apparent). Five questions
      measured what respondents would disclose using scripted statements. RESULTS: Wide
      variation existed regarding what information respondents would disclose. Of the
      respondents, 56% chose statements that mentioned the adverse event but not the
      error, while 42% would explicitly state that an error occurred. Some physicians
      disclosed little information: 19% would not volunteer any information about the
      error's cause, and 63% would not provide specific information about preventing
      future errors. Disclosure was affected by the nature of the error and physician
      specialty. Of the respondents, 51% who received the more apparent errors
      explicitly mentioned the error, compared with 32% who received the less apparent
      errors (P<.001); 58% of medical specialists explicitly mentioned the error,
      compared with 19% of surgical specialists (P<.001). Respondents disclosed more
      information if they had positive disclosure attitudes, felt responsible for the
      error, had prior positive disclosure experiences, and were Canadian. CONCLUSIONS:
      Physicians vary widely in how they would disclose errors to patients. Disclosure
      standards and training are necessary to meet public expectations and promote
      professional responsibility following errors.

PMID- 16908790
TI  - Association of new-onset breast discomfort with an increase in mammographic
      density during hormone therapy.
AB  - BACKGROUND: Postmenopausal use of estrogen and progestin therapy increases breast
      density and breast discomfort. Whether this increase in breast density is
      heralded by new-onset breast discomfort is unknown. METHODS: We used data from
      the Postmenopausal Estrogen/Progestin Interventions Mammographic Density Study,
      which retrieved and examined baseline and 12-month mammograms for 594 (67.9%) of
      875 women aged 45 to 64 years enrolled in the randomized controlled trial.
      Treatments included placebo, 0.625 mg/d of conjugated equine estrogens, 0.625
      mg/d of conjugated equine estrogens and medroxyprogesterone acetate (10 mg/d for
      12 d/mo or 2.5 mg/d continuously), or 0.625 mg/d of conjugated equine estrogens
      and 200 mg/d of micronized progestin for 12 d/mo. Breast density (the percent of
      the breast composed of dense tissue) was calculated from digitized mammograms
      obtained at baseline and at 12-month follow-up. Breast discomfort was ascertained
      at baseline and at follow-up using standardized self-report questionnaires. In
      bivariate analysis, and then in multivariable linear regression models, we
      assessed the association between change in percent breast density from baseline
      to 12-month follow-up and new-onset breast discomfort in participants who had no
      breast discomfort at baseline (N = 533). RESULTS: After adjustment for age,
      treatment assignment (placebo, conjugated equine estrogens, or progestin
      containing regimen), and other potential confounders, women with new-onset breast
      discomfort had a 3.9% increase in percent breast density compared with a 0.6%
      increase in percent breast density among women without new-onset breast
      discomfort (beta = .033, P<.001). The association between incident breast
      discomfort and increased percent breast density was similar in all active
      treatment arms. CONCLUSION: In postmenopausal women randomly assigned to
      menopausal hormone therapy vs placebo, new-onset breast discomfort is associated
      with increased mammographic density.

PMID- 16908792
TI  - Resident approaches to advance care planning on the day of hospital admission.
AB  - BACKGROUND: Advance care planning is the process of establishing a patient's
      goals and preferences for future care. Previous research has demonstrated a need
      to improve patient-physician communication around advance care planning. A
      critical time for advance care planning conversations is the day of admission to
      the hospital. METHODS: A survey of internal medicine residents was administered
      at Duke University Medical Center and the Brigham and Women's Hospital, 2 major
      academic teaching centers. Residents were questioned about their approaches to
      advance care planning on their last on-call admitting day. RESULTS: Of 347
      residents solicited, 292 (84.1%) participated in the survey. Residents reported
      that they established preferences for cardiopulmonary resuscitation (CPR) with
      70.5% of patients, established a health care proxy with 33.7% of patients,
      discussed goals and values concerning end-of-life care with 32.0% of patients,
      and asked 35.6% of patients if they had an advance directive. Although 89.0% of
      residents had observed an advance care planning discussion model, only 66.4% had
      received teaching and 36.6% had received feedback about advance care planning
      conversations. In multivariable analysis, having received feedback about advance
      care planning conversations was associated with a higher percentage of
      conversations about health care proxy and goals and values related to the end of
      life. CONCLUSIONS: Residents discuss patient preferences for CPR on the day of
      admission with most patients. Preparing residents, particularly through feedback,
      may improve communication around other elements of advance care planning.

PMID- 16908793
TI  - US and Canadian physicians' attitudes and experiences regarding disclosing errors
      to patients.
AB  - BACKGROUND: Patients are often not told about harmful medical errors. The
      malpractice environment is considered a major determinant of physicians'
      willingness to disclose errors to patients. Yet, little is known about the
      malpractice environment's actual effect on physicians' error disclosure attitudes
      and experiences. METHODS: Mailed survey of 2637 physicians (62.9% response rate)
      in the United States (Missouri and Washington) and Canada, countries with
      different malpractice environments. RESULTS: Physicians' error disclosure
      attitudes and experiences were similar across country and specialty. Of the
      physicians, 64% agreed that errors are a serious problem. However, 50% disagreed
      that errors are usually caused by system failures. Ninety-eight percent endorsed
      disclosing serious errors to patients and 78% supported disclosing minor errors;
      74% thought disclosing a serious error would be very difficult. Fifty-eight
      percent had disclosed a serious error to a patient, and 85% were satisfied with
      the disclosure, and 66% agreed that disclosing a serious error reduces
      malpractice risk. Respondents' estimates of the probability of lawsuits were not
      associated with their support for disclosure. The belief that disclosure makes
      patients less likely to sue (odds ratio, 1.58), not being in private practice
      (odds ratio, 1.47), being Canadian (odds ratio, 1.43), and being a surgeon (odds
      ratio, 1.26) were independently associated with higher support for disclosing
      serious errors. CONCLUSIONS: US and Canadian physicians' error disclosure
      attitudes and experiences are similar despite different malpractice environments,
      and reveal mixed feelings about disclosing errors to patients. The medical
      profession should address the barriers to transparency within the culture of
      medical and surgical specialties.

PMID- 16908794
TI  - Admission blood glucose level and mortality among hospitalized nondiabetic
      patients with heart failure.
AB  - BACKGROUND: The significance of admission blood glucose level in nondiabetic
      patients with heart failure (HF) is unknown. We examined the possible association
      between admission glucose levels and outcome in a large cohort of hospitalized
      patients with HF. METHODS: We analyzed the data of 4102 patients with HF, who
      were hospitalized during a prospective national survey. The present study focuses
      on a subgroup of 1122 nondiabetic patients with acute HF who were admitted
      because of acute HF or exacerbation of chronic HF. RESULTS: In-hospital mortality
      was twice as high in patients with admission blood glucose levels in the third
      tertile (7.2%) compared with the first (3%) and second (4%) tertiles (P = .02).
      Furthermore, mortality risk was correlated with admission glucose levels; each 18
      mg/dL (1-mmol/L) increase in glucose level was associated with a 31% increased
      risk of in-hospital mortality (adjusted odds ratio, 1.31; 95% confidence
      interval, 1.10-1.57; P = .003) and a 12% increase in 60-day mortality (adjusted
      hazard ratio, 1.12; 95% confidence interval, 1.01-1.25; P = .04). Admission blood
      glucose levels remained an independent predictor of in-hospital and 60-day
      mortality even after the exclusion of 315 patients (28%) with acute myocardial
      infarction and HF. The 6- and 12-month mortality rates were similar in patients
      with and without abnormal admission blood glucose levels. CONCLUSIONS: Elevated
      admission blood glucose levels are associated with increased in-hospital and 60
      day mortality, but not 6-month or 1-year mortality, in nondiabetic patients
      hospitalized because of HF.

PMID- 16908795
TI  - A randomized trial comparing human e-mail counseling, computer-automated tailored
      counseling, and no counseling in an Internet weight loss program.
AB  - BACKGROUND: Several studies have shown that e-mail counseling improves weight
      loss achieved in self-directed Internet programs. Computer-tailored feedback
      offers a population-based alternative to human e-mail counseling. METHODS: One
      hundred ninety-two adults, aged 49.2 +/- 9.8 years, having a body mass index
      (calculated as weight in kilograms divided by height in meters squared) of 32.7
      +/- 3.5, were randomized to 1 of 3 Internet treatment groups: No counseling,
      computer-automated feedback, or human e-mail counseling. All participants
      received 1 weight loss group session, coupons for meal replacements, and access
      to an interactive Web site. The human e-mail counseling and computer-automated
      feedback groups also had access to an electronic diary and message board. The
      human e-mail counseling group received weekly e-mail feedback from a counselor,
      and the computer-automated feedback group received automated, tailored messages.
      RESULTS: Retention was 82% at 3 months and 80% at 6 months for all 3 groups. At 3
      months, completers in both the computer-automated feedback (-5.3 +/- 4.2 kg) and
      human e-mail counseling (-6.1 +/- 3.9 kg) groups had significantly greater weight
      losses compared with the no counseling group (-2.8 +/- 3.5 kg) and these groups
      did not differ from each other. At 6 months, weight losses were significantly
      greater in the human e-mail counseling group (-7.3 +/- 6.2 kg) than in the
      computer-automated feedback (-4.9 +/- 5.9 kg) or no counseling (-2.6 +/- 5.7 kg)
      groups. Intent-to-treat analyses using single or multiple imputation techniques
      showed the same pattern of significance. CONCLUSIONS: Providing automated
      computer-tailored feedback in an Internet weight loss program was as effective as
      human e-mail counseling at 3 months. Further research is needed to improve the
      efficacy of automated computer-tailored feedback as a population-based weight
      loss approach.

PMID- 16908796
TI  - Use of flexible sigmoidoscopy to screen for colorectal cancer in HIV-infected
      patients 50 years of age and older.
AB  - BACKGROUND: Although many patients with human immunodeficiency virus (HIV)
      infection are now living well beyond 50 years of age, there are no data available
      on colorectal cancer screening in this population. The aim of this study was to
      determine the utility of screening flexible sigmoidoscopy in patients with HIV.
      METHODS: Consecutive patients at average risk for colorectal cancer who were
      referred for screening flexible sigmoidoscopy were prospectively identified. A
      detailed medical history was obtained from all patients before flexible
      sigmoidoscopy, and colonoscopy was recommended for all subjects with positive
      sigmoidoscopic findings. RESULTS: A total of 2382 patients were enrolled in the
      study; 165 were HIV positive. The prevalence of neoplastic lesions (adenomas or
      adenocarcinomas) in the distal colon was significantly higher in HIV-infected
      patients than in control subjects (25.5% vs 13.1%, P<.001), and the odds of HIV
      infected patients having a neoplastic lesion was significantly higher even after
      adjustment for potential confounding variables (odds ratio, 2.34; 95% confidence
      interval, 1.60-3.44). The prevalence of adenomas of any size (25.5% vs 12.9%,
      P<.001) and advanced neoplasia (7.3% vs 3.8%, P = .03) in the distal colon was
      significantly higher in HIV-infected patients. Among individuals with positive
      results on flexible sigmoidoscopy, proximal colonic neoplastic lesions on follow
      up colonoscopy were more common in HIV-infected patients after adjustment for
      age, sex, and race/ethnicity (odds ratio, 1.88; 95% confidence interval, 1.02
      3.46). CONCLUSIONS: Patients infected with HIV are more likely to have colonic
      neoplasms on screening flexible sigmoidoscopy than those without HIV, and these
      individuals should be offered colorectal cancer screening.

PMID- 16908797
TI  - Liver-related deaths in persons infected with the human immunodeficiency virus:
      the D:A:D study.
AB  - BACKGROUND: An increasing proportion of deaths among human immunodeficiency virus
      (HIV)-infected persons with access to combination antiretroviral therapy (cART)
      are due to complications of liver diseases. METHODS: We investigated the
      frequency of and risk factors associated with liver-related deaths in the Data
      Collection on Adverse Events of Anti-HIV Drugs study, which prospectively
      evaluated 76 893 person-years of follow-up in 23 441 HIV-infected persons.
      Multivariable Poisson regression analyses identified factors associated with
      liver-related, AIDS-related, and other causes of death. RESULTS: There were 1246
      deaths (5.3%; 1.6 per 100 person-years); 14.5% were from liver-related causes. Of
      these, 16.9% had active hepatitis B virus (HBV), 66.1% had hepatitis C virus
      (HCV), and 7.1% had dual viral hepatitis co-infections. Predictors of liver
      related deaths were latest CD4 cell count (adjusted relative rate [RR], 16.1; 95%
      confidence interval [CI], 8.1-31.7 for <50 vs > or =500/microL), age (RR, 1.3;
      95% CI, 1.2-1.4 per 5 years older), intravenous drug use (RR, 2.0; 95% CI, 1.2
      3.4), HCV infection (RR, 6.7; 95% CI, 4.0-11.2), and active HBV infection (RR,
      3.7; 95% CI, 2.4-5.9). Univariable analyses showed no relationship between
      cumulative years patients were receiving cART and liver-related death (RR, 1.00;
      95% CI, 0.93-1.07). Adjustment for the most recent CD4 cell count and patient
      characteristics resulted in an increased risk of liver-related mortality per year
      of mono or dual antiretroviral therapy before cART (RR, 1.09; 95% CI, 1.02-1.16;
      P = .008) and per year of cART (RR, 1.11; 95% CI, 1.02-1.21; P = .02).
      CONCLUSIONS: Liver-related death was the most frequent cause of non-AIDS-related
      death. We found a strong association between immunodeficiency and risk of liver
      related death. Longer follow-up is required to investigate whether clinically
      significant treatment-associated liver-related mortality will develop.

PMID- 16908798
TI  - Etiology and outcome of fever after a stay in the tropics.
AB  - BACKGROUND: Information on epidemiology and prognosis of imported fever is scarce
      and almost exclusively limited to hospital settings. METHODS: From 2000 to 2005,
      all travelers presenting at our referral outpatient and inpatient centers with
      ongoing fever within 12 months after a stay in the tropics were prospectively
      followed. Case definitions and treatment were based on international
      recommendations. Outcome was assessed by at least 1 follow-up consultation or
      telephone call within 3 months after initial contact. RESULTS: A total of 1842
      fever episodes were included, involving 1743 patients. Regions of exposure were
      mainly sub-Saharan Africa (68%) and the Southeast Asia-Pacific region (12%).
      Tropical diseases accounted for 39% of all cases and cosmopolitan infections for
      34%. Diagnosis often remained unknown (24%). The pattern of tropical diseases was
      mainly influenced by the travel destination, with malaria (35%, mainly Plasmodium
      falciparum) and rickettsial infection (4%) as the leading diagnoses after a stay
      in Africa; dengue (12%), malaria (9%), and enteric fever (4%) after travel to
      Asia; and dengue (8%) and malaria (4%) on return from Latin America. Disease
      pattern varied also according to the category of travelers, the delay between
      exposure and fever onset, and the setting. Hospitalization was required for 503
      fever episodes (27%). Plasmodium falciparum malaria accounted for 36% of all
      admissions and was the only tropical cause of death (5 of 9 patients). Fever of
      unknown cause had invariably a favorable outcome. CONCLUSION: The clinical
      spectrum of imported fever is highly destination specific but also depends on
      other factors. Plasmodium falciparum malaria was the leading cause of mortality
      in the study population.

PMID- 16908799
TI  - Chronic widespread pain and its comorbidities: a population-based study.
AB  - BACKGROUND: Chronic widespread pain (CWP), the cardinal symptom of fibromyalgia,
      is prevalent and co-occurs with numerous symptom-based conditions such as chronic
      fatigue syndrome, joint pain, headache, irritable bowel syndrome, and psychiatric
      disorders. Few studies have examined the comorbidities of CWP in the general
      population. Furthermore, little is known about the importance of familial
      (genetic and family environmental) factors in the etiology of co-occurrence.
      METHODS: Data were obtained from 44 897 individuals in the Swedish Twin Registry
      via computer-assisted telephone interview from 1998 through 2002 (age >/=42
      years; 73.2% response rate). Screening for CWP was based on the American College
      of Rheumatology criteria without clinical evaluation. Measures for comorbidities
      were based on standard criteria when available. Odds ratios (ORs) were calculated
      in case-control and co-twin control designs to assess the effect of familial
      confounding in the associations. RESULTS: Considerable co-occurrences were found
      in CWP cases for chronic fatigue (OR, 23.53; 95% confidence interval [CI], 19.67
      28.16), joint pain (OR, 7.41; 95% CI, 6.70-8.21), depressive symptoms (OR, 5.26;
      95% CI, 4.75-5.82), and irritable bowel syndrome (OR, 5.17; 95% CI, 4.55-5.88).
      In co-twin control analyses, ORs were no longer significant for psychiatric
      disorders, whereas they decreased but remained significant for most other
      comorbidities. No changes in ORs were observed for headache. CONCLUSIONS:
      Associations between CWP and most comorbidities are mediated by unmeasured
      genetic and family environmental factors in the general population. The extent of
      mediation via familial factors is likely to be disorder specific.

PMID- 16908800
TI  - Homozygosity in the single nucleotide polymorphism Ser128Arg in the E-selectin
      gene associated with recurrent venous thromboembolism.
AB  - BACKGROUND: The single nucleotide polymorphism (SNP) Ser128Arg in the E-selectin
      gene is overrepresented in certain patient populations with atherosclerosis or
      restenosis. As this SNP enhances tissue factor-triggered coagulation in humans
      during systemic inflammation, we hypothesized that it may also predispose for the
      development of recurrent venous thromboembolism (VTE). METHODS: A total of 585
      patients were prospectively observed after first VTE for recurrent, objectively
      documented, symptomatic VTE. Patients with secondary VTE, homozygous factor V
      Leiden, natural inhibitor deficiencies, lupus anticoagulant, or long-term
      anticoagulation therapy were excluded. The S128R SNP was genotyped by
      mutagenically separated polymerase chain reaction. RESULTS: A total of 102
      patients (17%) were heterozygous, and 11 were homozygous (2%) for the Ser128Arg
      mutation. Ninety patients (15%) had recurrent VTE during follow-up. Homozygosity
      for the Ser128Arg SNP increased the cumulative likelihood, particularly for early
      recurrent VTE (log rank test, P<.05) and was an independent predictor of
      recurrent VTE (hazard ratio [HR], 4.1; 95% confidence interval [CI], 1.5-11.4) in
      a multivariate Cox regression model. In contrast, heterozygosity for the
      polymorphism was associated with an unaltered HR (HR, 1.1; 95% CI, 0.6-1.9) for
      recurrent VTE. CONCLUSIONS: Homozygosity for the S128R E-selectin allele appears
      to increase the risk for recurrent VTE several fold. If these findings are
      confirmed, this may represent a novel risk factor for recurrent VTE. These
      results also expand our knowledge on the association of this SNP with thrombotic
      disorders.

PMID- 16908801
TI  - Low serum testosterone and mortality in male veterans.
AB  - BACKGROUND: Low serum testosterone is a common condition in aging associated with
      decreased muscle mass and insulin resistance. This study evaluated whether low
      testosterone levels are a risk factor for mortality in male veterans. METHODS: We
      used a clinical database to identify men older than 40 years with repeated
      testosterone levels obtained from October 1, 1994, to December 31, 1999, and
      without diagnosed prostate cancer. A low testosterone level was a total
      testosterone level of less than 250 ng/dL (<8.7 nmol/L) or a free testosterone
      level of less than 0.75 ng/dL (<0.03 nmol/L). Men were classified as having a low
      testosterone level (166 [19.3%]), an equivocal testosterone level (equal number
      of low and normal levels) (240 [28.0%]), or a normal testosterone level (452
      [52.7%]). The risk for all-cause mortality was estimated using Cox proportional
      hazards regression models, adjusting for demographic and clinical covariates over
      a follow-up of up to 8 years. RESULTS: Mortality in men with normal testosterone
      levels was 20.1% (95% confidence interval [CI], 16.2%-24.1%) vs 24.6% (95% CI,
      19.2%-30.0%) in men with equivocal testosterone levels and 34.9% (95% CI, 28.5%
      41.4%) in men with low testosterone levels. After adjusting for age, medical
      morbidity, and other clinical covariates, low testosterone levels continued to be
      associated with increased mortality (hazard ratio, 1.88; 95% CI, 1.34-2.63;
      P<.001) while equivocal testosterone levels were not significantly different from
      normal testosterone levels (hazard ratio, 1.38; 95% CI, 0.99%-1.92%; P=.06). In a
      sensitivity analysis, men who died within the first year (50 [5.8%]) were
      excluded to minimize the effect of acute illness, and low testosterone levels
      continued to be associated with elevated mortality. CONCLUSIONS: Low testosterone
      levels were associated with increased mortality in male veterans. Further
      prospective studies are needed to examine the association between low
      testosterone levels and mortality.

PMID- 16908802
TI  - Represcription after adverse drug reaction in the elderly: a descriptive study.

PMID- 16908803
TI  - Erectile dysfunction.

PMID- 16908804
TI  - N-acetylcysteine for contrast nephropathy: more clinical science is required.

PMID- 16908805
TI  - From chaotic to coordinated clinical research: the case of acetylcysteine.

PMID- 16908806
TI  - Smoking and risk for colorectal cancer.

PMID- 16908807
TI  - Smoking and age at cancer diagnosis.

PMID- 16908808
TI  - The age-at-diagnosis fallacy.

PMID- 16908809
TI  - The dogma of "tight control": beyond the limits of evidence.

PMID- 16908810
TI  - The course of glaucoma during pregnancy: a retrospective case series.
AB  - OBJECTIVE: To better understand the course of glaucoma during pregnancy in women
      with preexisting disease. METHODS: Retrospective case series of 28 eyes of 15
      women with glaucoma followed up during pregnancy. Data were analyzed for age,
      race/ethnicity, medications, glaucoma type, intraocular pressure (IOP), and
      visual fields before, during, and after pregnancy. RESULTS: In 16 (57.1%) of 28
      eyes, IOP was stable during pregnancy, with no progression of visual field loss.
      In 5 eyes (17.9%), visual field loss progressed during pregnancy, while IOP
      remained stable or increased. In 5 eyes (17.9%), IOP increased during pregnancy,
      but there was no progression of visual field loss. In 2 eyes (7.1%), data were
      inconclusive because of medication noncompliance and preexisting severe visual
      field loss. Glaucoma medications were used by 13 of 15 patients to control
      glaucoma during pregnancy. The classes of medications used most frequently were
      beta-blockers, alpha2-adrenergic agents, cholinergic agents, and topical carbonic
      anhydrase inhibitors. CONCLUSIONS: The course of glaucoma during pregnancy is
      variable, and women must be monitored closely during pregnancy. Medications may
      be necessary to control IOP and to prevent vision loss during pregnancy.

PMID- 16908811
TI  - In vivo confocal microscopy of filtering blebs after trabeculectomy.
AB  - OBJECTIVES: To analyze filtering blebs after trabeculectomy by means of in vivo
      confocal microscopy and to correlate the images with clinical bleb appearance and
      function. METHOD: In vivo confocal microscopy using the Heidelberg Retina
      Tomograph/Rostock Cornea Module (Heidelberg Engineering, Heidelberg, Germany) was
      performed in 53 filtering blebs in 45 patients 6 days to 30 years
      postoperatively. RESULTS: In vivo confocal microscopic findings significantly
      correlated with good bleb function included the number of epithelial microcysts
      (P = .03), a large total stromal cyst area (P = .009), the absence of
      encapsulated stromal cysts (P = .002), minimal vascularization (P = .05), and the
      absence of tortuous conjunctival vessels (P = .01). In contrast, a
      hyperreflective condensed bleb stroma was significantly associated with bleb
      failure (P<.001). Bleb stroma mainly consisting of a rarified collagenlike
      network was significantly linked to trabeculectomy performed with mitomycin C (P
      = .001). Epithelial and stromal inflammation were observed at a median of 1 and 4
      months after surgery, respectively. CONCLUSIONS: In vivo confocal microscopy
      using the Heidelberg Retina Tomograph/Rostock Cornea Module permits diagnostic
      imaging of filtering blebs and differentiation between good and insufficient bleb
      function. Moreover, the postoperative inflammatory reaction can be monitored
      directly for adapted postoperative anti-inflammatory treatment.

PMID- 16908812
TI  - Ocular pulse amplitude in healthy subjects as measured by dynamic contour
      tonometry.
AB  - OBJECTIVES: To test whether dynamic contour tonometry yields ocular pulse
      amplitude (OPA) measurements that are independent of corneal thickness and
      curvature, and to assess variables of observer agreement. METHODS: In a
      multivariate cluster analysis on 223 eyes, the relationship between central
      corneal thickness, corneal curvature, axial length, anterior chamber depth,
      intraocular pressure, sex, age, and OPA measurements was assessed. Intraobserver
      and interobserver variabilities were calculated from repeated measurements
      obtained from 8 volunteers by 4 observers. RESULTS: The OPA readings were not
      affected by central corneal thickness (P = .08), corneal curvature (P = .47),
      anterior chamber depth (P = .80), age (P = .60), or sex (P = .73). There was a
      positive correlation between OPA and intraocular pressure (0.12 mm Hg/1 mm Hg of
      intraocular pressure; P<.001) and a negative correlation between OPA and axial
      length (0.27 mm Hg/1 mm of length; P<.001). Intraobserver and interobserver
      variabilities were 0.08 and 0.02 mm Hg, respectively, and the intraclass
      correlation coefficient was 0.89. CONCLUSIONS: The OPA readings obtained with
      dynamic contour tonometry in healthy subjects are not influenced by the structure
      of the anterior segment of the eye but are affected by intraocular pressure and
      axial length. We found a high amount of agreement within and between observers.

PMID- 16908813
TI  - Detection and quantification of retinal nerve fiber layer thickness in optic disc
      edema using stratus OCT.
AB  - OBJECTIVE: To investigate the ability of optical coherence tomography (OCT) to
      assess changes in retinal nerve fiber layer (RNFL) thickness in optic disc edema.
      METHODS: Prospective observational case series in a private eye clinic (Centro
      Salus). Twelve consecutive eyes (9 patients) with optic disc edema were analyzed,
      including 6 patients with anterior ischemic optic neuropathy, 1 patient with
      multiple sclerosis-associated papillitis, and 2 patients with bilateral
      papilledema. Peripapillary scans of the RNFL were obtained using Stratus OCT
      (software version 3.0; Carl Zeiss Meditec, Dublin, Calif). Repeated measurements
      were performed in 7 patients during a follow-up ranging from 8 to 30 weeks. The
      main outcome was RNFL thickness measurement. RESULTS: Optical coherence
      tomography detected and quantified diffuse thickening of the RNFL. Compared with
      eyes in a control group of 75 healthy subjects, eyes with optic disc edema showed
      a significant increase in the mean RNFL thickness in all quadrants (temporal, P =
      .002; superior, P<.001; nasal, P<.001; and inferior, P<.001). In patients who
      were followed up, progressive thinning was observed as the disease evolved toward
      optic atrophy or clinical resolution. CONCLUSIONS: Optical coherence tomography
      can identify and measure RNFL edema. This ability of OCT may help elucidate
      pathophysiological mechanisms in optic disc edema and provide a valuable aid to
      clinicians.

PMID- 16908814
TI  - Monitoring visual function in children with syndromic craniosynostosis: a
      comparison of 3 methods.
AB  - OBJECTIVE: To compare visual acuity, optic disc appearance, and transient pattern
      reversal visual evoked potentials as markers of possible visual dysfunction in
      children with syndromic craniosynostosis. METHODS: Serial visual acuity, optic
      disc appearance, and pattern reversal visual evoked potential data were recorded
      in 8 patients with syndromic craniosynostosis before and after cranial vault
      expansion. The pattern reversal visual evoked potentials were analyzed using
      linear regression modeling, applied to the N80 to P100 amplitude. RESULTS: Serial
      optic disc appearances were available for all 8 patients and visual acuities for
      7 patients. The visual acuity deteriorated in only 1 patient, improved in 4, and
      fluctuated in 2, before surgery. Of the 8 patients, 3 showed no papilledema in
      either eye at any time, 3 showed progressive bilateral swelling before surgery,
      and 2 exhibited only unilateral disc swelling. In all 8 patients, there was a
      trend for the N80 to P100 amplitude to decrease before surgery and to increase,
      in all but 2 patients, after surgery. CONCLUSIONS: This study suggests that
      neither optic disc appearance nor visual acuity assessment alone is a reliable
      marker of potential visual dysfunction in children with syndromic
      craniosynostosis. It also suggests that the pattern reversal visual evoked
      potential can provide early evidence of visual dysfunction before vault expansion
      surgery in these children; this dysfunction may recover postoperatively.

PMID- 16908815
TI  - Hypertropia associated with superolateral translation of the superior rectus
      muscle pulley in unilateral coronal synostosis.
AB  - OBJECTIVE: To explore the mechanisms underlying the hypertropia associated with
      unilateral coronal synostosis. METHODS: In 13 patients with unilateral coronal
      synostosis, we measured gaze-dependent binocular alignment before and after
      strabismus surgery, assessed the superior rectus muscle (SRM) pulley using
      computed tomography, and simulated posterior displacement of the trochlea and
      superolateral displacement of the SRM pulley. RESULTS: All the patients had an
      ipsilateral hypertropia in primary gaze (3-30 diopters) that increased in
      contralateral gaze and decreased in ipsilateral gaze and that simulated an
      inferior oblique muscle overaction. Strabismus surgery fully or partially
      corrected the hypertropia in only 7 of 11 patients. High-resolution computed
      tomography demonstrated that the pulley of the SRM relative to the inferior
      rectus muscle was translated 0 to 11.0 mm laterally and up to 2.7 mm vertically.
      Lateral translation (up to 10 mm) alone or combined with vertical translation (up
      to 5 mm) of the SRM pulley in the simulated model produced a hypertropia with
      lateral incomitance. Posterior translation (15 mm) of the trochlea did not induce
      a significant hypertropia. CONCLUSION: Superolateral translation of the SRM
      pulley creates an imbalance of muscle pulling forces that better accounts for the
      hypertropia than posterior displacement of the trochlea.

PMID- 16908816
TI  - Evaluation of the SmartCycler II system for real-time detection of viruses and
      Chlamydia from ocular specimens.
AB  - OBJECTIVE: To compare the SmartCycler II system (Cepheid, Sunnyvale, Calif)
      results with those of standard cell culture, to compare the SmartCycler II system
      results with those of a dedicated polymerase chain reaction facility, and to
      establish the SmartCycler II system as a polymerase chain reaction method for
      detecting viral and chlamydial DNA from ocular specimens. METHODS: True-positive
      samples (test-positive specimens based on standard testing) and true-negative
      samples (test-negative specimens based on standard testing) were processed for
      polymerase chain reaction using the SmartCycler II system for adenovirus, herpes
      simplex virus type 1, varicella-zoster virus, and Chlamydia trachomatis.
      Sensitivity, specificity, positive predictive value, negative predictive value,
      and efficiency were based on the testing of true-positive and true-negative
      specimens. RESULTS: The descriptive statistics for adenovirus, herpes simplex
      virus type 1, varicella-zoster virus, and C trachomatis were, respectively, as
      follows: sensitivity, 85%, 98%, 100%, and 94%; specificity, 98%, 100%, 100%, and
      100%; positive predictive value, 98%, 100%, 100%, and 100%; negative predictive
      value, 85%, 91%, 100%, and 98%; and efficiency, 92%, 95%, 100%, and 99%. Test
      sensitivity for the SmartCycler II system was equivalent to that from a central
      molecular laboratory. CONCLUSION: The descriptive statistics of the SmartCycler
      II system obtained in a small laboratory were comparable to those of a central
      molecular laboratory for detecting viruses and Chlamydia species. Clinical
      Relevance Polymerase chain reaction has great potential in the routine diagnosis
      of ocular infections in any conventional laboratory.

PMID- 16908817
TI  - Effect of P2X7 receptor activation on the retinal blood velocity of diabetic
      rabbits.
AB  - OBJECTIVE: To test the effect of activation of P2X7 receptors on retinal blood
      velocity in diabetic rabbits. METHODS: Immunohistochemical analysis was performed
      on healthy and diabetic rabbit eyes using P2X7 receptor antibodies. Diabetes was
      induced using alloxan. Retinal blood velocity was measured with the laser speckle
      circulation analyzer. Visual function was assessed using electroretinography.
      RESULTS: Cells in inner retinal layers were positive for anti-P2X7 receptor
      antibodies in healthy rabbits. The distribution of positive cells extended to
      outer layers and some small vessels stained in diabetic rabbits. When assayed 24
      hours after an intravitreal injection of 150 nmol of benzoylbenzoyl adenosine
      triphosphate (BzATP), a P2X7 agonist, the retinal blood velocity in healthy
      rabbits was reduced by approximately 30%; this reduction continued for at least 4
      weeks. Only in diabetic rabbits did an injection of 50 nmol of BzATP reduce
      retinal blood velocity by approximately 30% and the amplitudes of
      electroretinography a waves, b waves, and oscillatory potentials for at least 4
      weeks. CONCLUSIONS: Soon after the onset of alloxan-induced diabetes, retinal
      blood velocity and function become more vulnerable to reduction initiated through
      P2X7 receptors. CLINICAL RELEVANCE: Our findings support the hypothesis that the
      retinal circulation disorder accelerated by activation of P2X7 receptors may be
      involved in the early changes of diabetic retinopathy.

PMID- 16908818
TI  - Associations between intermediate age-related macular degeneration and lutein and
      zeaxanthin in the Carotenoids in Age-related Eye Disease Study (CAREDS):
      ancillary study of the Women's Health Initiative.
AB  - OBJECTIVE: To evaluate the relationship between dietary lutein plus zeaxanthin
      and intermediate age-related macular degeneration (AMD). DESIGN: Women aged 50 to
      79 years in Iowa, Wisconsin, and Oregon with intake of lutein plus zeaxanthin
      above the 78th (high) and below the 28th (low) percentiles at baseline in the
      Women's Health Initiative Observational Study were recruited 4 to 7 years later
      into the Carotenoids in Age-Related Eye Disease Study (CAREDS), when the presence
      of AMD was determined by fundus photographs. Logistic regression analyses
      examined the prevalence of AMD in 1787 CAREDS participants, after accounting for
      potential covariates. RESULTS: The prevalence of intermediate AMD was not
      statistically different between the high and low lutein plus zeaxanthin intake
      recruitment groups after adjusting for age (odds ratio, 0.96; 95% confidence
      interval, 0.75-1.23). Limiting analyses to women younger than 75 years with
      stable intake of lutein plus zeaxanthin, without a history of chronic diseases
      that are often associated with diet changes, substantially lowered odds ratios
      (0.57; 95% confidence interval, 0.34-0.95). Exploratory analyses of advanced AMD
      in 34 participants resulted in protective, but statistically nonsignificant,
      associations in the overall sample and in women younger than 75 years.
      CONCLUSION: Diets rich in lutein plus zeaxanthin may protect against intermediate
      AMD in healthy women younger than 75 years.

PMID- 16908819
TI  - Retinal vein occlusion associated with antithrombin deficiency secondary to a
      novel G9840C missense mutation.
AB  - OBJECTIVE: To describe a novel missense mutation in the antithrombin gene
      associated with antithrombin deficiency type I in a 40-year-old man with retinal
      vein occlusion. DESIGN: Investigational case report. RESULTS: Ophthalmoscopy of
      the right eye showed hemicentral retinal vein occlusion. The patient's medical
      history was negative for glaucoma or cardiovascular risk factors. Screening for
      thrombophilic disorders revealed antithrombin deficiency type I. Based on a
      genetic analysis, a novel missense mutation of a transition of guanosine to
      cytosine at nucleotide position 9840 was detected, predicting the replacement of
      aspartic acid by histidine encoded by codon 366 (D366H) in exon 5. CONCLUSIONS:
      Selective screening may be helpful in identifying patients with retinal vein
      occlusion with thrombophilic defects. When ordering laboratory tests in patients
      with retinal vein occlusion, antithrombin deficiency type I should be considered
      in the differential diagnosis. CLINICAL RELEVANCE: Our results contribute to a
      better understanding of the molecular bases of antithrombin deficiency, adding a
      novel entry for the molecular defects causing antithrombin deficiency type I.
      Moreover, the identification of this thrombophilic disorder in retinal vein
      occlusion may be relevant to the issue of the initiation and duration of oral
      anticoagulant therapy.

PMID- 16908820
TI  - A technique for medial canthal fixation using resorbable poly-L-lactic acid
      polyglycolic acid fixation kit.
AB  - Achieving secure bony fixation of medial canthus is a challenge. We used a
      resorbable poly-L-lactic acid-polyglycolic acid screw (LactoSorb office fixation
      kit) in 5 cases: 2 with traumatic medial canthal dystopia, 1 with scleroderma and
      orbital fat atrophy causing malapposition of the medial canthus to globe, and 2
      with invasive medial canthal tumors necessitating subtotal medial orbital
      exenteration. The resorbable screw with preplaced suture was drilled into the
      medial orbital wall, using a handheld self-drilling tap. The preplaced suture was
      used to anchor the medial canthus. We achieved satisfactory canthal position in
      all 5 cases. There were no complications in 4 cases during a mean +/- SD follow
      up of 11.3 +/- 6 months; however, the scleroderma case developed wound dehiscence
      6 weeks after surgery. The LactoSorb kit is a safe and effective technique to
      achieve bony medial canthal fixation in carefully selected cases.

PMID- 16908821
TI  - Medicare prescription drug cards: effectiveness for patients with glaucoma.
AB  - OBJECTIVE: To assess the level of discounts on glaucoma medications provided by
      the Medicare prescription drug card program. METHODS: We compared the cost of a 1
      month supply of 10 brand-name drugs and 1 commonly prescribed combination of
      drugs purchased at retail cash price, Medicare card-discounted price, and online
      price. Retail cash prices were collected through a telephone survey of 36 chain
      pharmacies in 4 states. Card-discounted prices were obtained from an online
      database updated weekly by Medicare for each drug, drug card, and state in our
      survey. Prices for drugs purchased online were collected from a leading online
      drugstore not affiliated with any retail stores that were included in the
      telephone survey. RESULTS: Card-discounted prices for each drug ranged between
      13% and 25% lower on average than retail prices. However, drugs purchased online
      were cheaper on average than drugs purchased with cards for 7 of the 10
      medications surveyed. CONCLUSIONS: Drug cards provide significant discounts over
      retail prices. However, cards may be a secondary option to online purchasing,
      which may be cheaper and may offer seniors more flexibility to switch between
      glaucoma therapies. Ophthalmologists can take simple steps to guide seniors to
      the optimal purchasing option for a given drug in their region.

PMID- 16908822
TI  - Fusarium keratitis associated with soft contact lens wear.

PMID- 16908823
TI  - How much influence do socioeconomic factors have on glaucoma prevalence and
      therapeutic outcomes?

PMID- 16908824
TI  - Conjunctival melanoma in children: a clinicopathologic study of 2 cases.

PMID- 16908825
TI  - Presumed choroidal langerhans cell histiocytosis following a previously resected
      solitary central nervous system lesion in an adult.

PMID- 16908826
TI  - Resolution of iris neovascularization following chemoreduction of advanced
      retinoblastoma.

PMID- 16908827
TI  - Surgical management of macular retinoschisis associated with high myopia.

PMID- 16908828
TI  - Contractile morning glory disc causing transient monocular blindness in a child.

PMID- 16908829
TI  - Macular exudative retinal detachment in a patient with a dural cavernous sinus
      fistula.

PMID- 16908830
TI  - Surgical management of unilateral glaucoma associated with poland sequence.

PMID- 16908831
TI  - Spontaneous regression of subretinal exudate in coats disease.

PMID- 16908832
TI  - Infliximab in uveitis treatment.

PMID- 16908833
TI  - Selection and analysis of spontaneous reciprocal mitotic cross-overs in
      Saccharomyces cerevisiae.
AB  - We developed a system that allows the selection of the reciprocal products
      resulting from spontaneous mitotic cross-overs in the yeast Saccharomyces
      cerevisiae. A number of other types of genetic events, including chromosome loss,
      can be monitored with this system. For a 120-kb chromosome interval on chromosome
      V (CEN5-CAN1), the rate of mitotic cross-overs was 4x10(-5) per division, a rate
      approximately 25,000-fold lower than the meiotic rate of cross-overs. We found no
      suppression of mitotic cross-overs near the centromere of chromosome V, unlike
      the suppression observed for meiotic exchanges. The rate of reciprocal cross
      overs was substantially (38-fold) elevated by treatment of cells with
      hydroxyurea, a drug that reduces nucleotide pools and slows DNA replication.

PMID- 16908834
TI  - Sexual acquisition of beneficial symbionts in aphids.
AB  - A noted cost of mating is the risk of acquiring sexually transmitted infections
      that are detrimental to the recipient. But many microbial associates of
      eukaryotes are mutualistic, raising the possibility that sexual contact provides
      the opportunity to acquire symbionts that are beneficial. In aphids, facultative
      bacterial symbionts, which benefit hosts by conferring resistance to natural
      enemies or to heat, are transmitted maternally with high fidelity and are
      maintained stably throughout hundreds of parthenogenetic generations in the
      laboratory. Data from field populations indicate that horizontal transfer of
      these facultative symbionts is frequent, and transfections are readily achieved
      by microinjection or ingestion in artificial diet. However, no natural mechanism
      for the horizontal transfer of these symbionts has been identified. Here we
      demonstrate that during sexual reproduction, male-borne symbionts can be acquired
      by females and subsequently transferred to sexually and parthenogenetically
      produced progeny, establishing stable, maternally transmitted associations. In
      our experiments, sexually transmitted symbionts resulted in (i) infection of
      previously uninfected matrilines, (ii) a double infection in a matriline already
      bearing a different symbiont, and (iii) replacement of the maternal symbiont. We
      also observed some cases in which maternal symbionts failed to become established
      in sexually produced progeny. Microscopy indicated that symbionts were abundant
      in the male reproductive system, which demonstrates a natural route of
      nonmaternal transfer of insect symbionts. Because such transfer can generate
      coinfections, thereby creating opportunities for symbiont competition and
      recombination, paternal inheritance has major consequences for expectations
      regarding symbiont evolution.

PMID- 16908836
TI  - Single gene control of a complex phenotype hangs in the balance.

PMID- 16908835
TI  - RNA polymerase II elongation factors Spt4p and Spt5p play roles in transcription
      elongation by RNA polymerase I and rRNA processing.
AB  - Previous investigations into the mechanisms that control RNA Polymerase (Pol) I
      transcription have primarily focused on the process of transcription initiation,
      thus little is known regarding postinitiation steps in the transcription cycle.
      Spt4p and Spt5p are conserved throughout eukaryotes, and they affect elongation
      by Pol II. We have found that these two proteins copurify with Pol I and
      associate with the rDNA in vivo. Disruption of the gene for Spt4p resulted in a
      modest decrease in growth and rRNA synthesis rates at the permissive temperature,
      30 degrees C. Furthermore, biochemical and EM analyses showed clear defects in
      rRNA processing. These data suggest that Spt4p, Spt5p, and, potentially, other
      regulators of Pol I transcription elongation play important roles in coupling
      rRNA transcription to its processing and ribosome assembly.

PMID- 16908837
TI  - Profile of Michael Karin.

PMID- 16908838
TI  - Cyclophosphamide enhances glioma virotherapy by inhibiting innate immune
      responses.
AB  - Clinical trials are testing oncolytic viruses (OVs) as therapies for cancer. We
      have shown that animals that have brain tumors and are treated with a herpes
      simplex virus (HSV)-derived OV live significantly longer when cyclophosphamide
      (CPA) is preadministered. Here, we explore the mechanisms behind this finding. In
      a syngeneic rat glioma model, intratumoral HSV administration is associated with
      rapid increase of natural killer cells, microglia/macrophages (CD68+ and CD163+),
      and IFN-gamma. Pretreatment with CPA enhances HSV replication and oncolysis and
      reduces an HSV-mediated increase in CD68+ and CD163+ cells and intratumoral IFN
      gamma. Molecular imaging shows CPA pretreatment to inhibit HSV-induced
      infiltration of tumor-associated phagocytic cells. Our results reveal molecular
      and cellular mechanisms that inhibit intratumoral spread of HSV and suggest a
      therapeutic path for improving the efficacy of virotherapy as a treatment for
      cancer.

PMID- 16908839
TI  - Fatness at birth predicts adult susceptibility to ovarian suppression: an
      empirical test of the Predictive Adaptive Response hypothesis.
AB  - Poor fetal environments are thought to produce adaptive changes in human
      developmental trajectories according to the Predictive Adaptive Response
      hypothesis. Although many studies have demonstrated correlations between
      indicators of fetal environment and negative adult health outcomes, the adaptive
      significance of these outcomes is unclear. Our study explicitly tests the
      adaptive nature of fetal programming in humans. We show that differences in
      nutritional status at birth are associated with adaptive differences in the
      sensitivity of adult ovarian function to energetic stress. Women who were born as
      relatively fat babies do not exhibit ovarian suppression in response to moderate
      levels of physical activity at adulthood, in contrast to women who were born as
      skinnier babies. The levels of estradiol in women born in the highest tertile of
      ponderal index (an indicator of neonatal nutritional status) were 37% and 46%
      higher, respectively, than levels of estradiol in women born in the low and
      middle ponderal index tertiles. These findings suggest that fetal programming of
      reproductive function results in developmentally plastic, but essentially
      adaptive, shifts in set points of ovarian response to energetic stress, such that
      women who were gestated under conditions of energetic constraint show greater
      sensitivity to energetic stress in adulthood. Our results have practical
      implications in terms of behavioral strategies for reducing the risk of breast
      cancer. We suggest that the amount of activity necessary to reduce levels of
      estrogen, which may in turn reduce cancer risk, can depend on a woman's
      nutritional status at birth.

PMID- 16908840
TI  - Sustainability science from space: quantifying forest disturbance and land-use
      dynamics in the Amazon.

PMID- 16908841
TI  - A FoxO-Smad synexpression group in human keratinocytes.
AB  - Transforming growth factor beta (TGF-beta) signals through activation of Smad
      transcription factors. Activated Smad proteins associate with different DNA
      binding cofactors for the recognition and regulation of specific target genes.
      Members of the forkhead box O family (FoxO1, FoxO3, and FoxO4) play such a role
      in the induction of the cyclin-dependent kinase inhibitors p15Ink4b and p21Cip1.
      To delineate the organization of the TGF-beta response in human keratinocytes, we
      defined the set of genes whose activation by TGF-beta requires both FoxO and Smad
      functions. FoxO factors are shown to be essential for 11 of the 115 immediate
      gene activation responses to TGF-beta in these cells. FoxO1, FoxO3, and FoxO4 act
      redundantly as mediators of these effects. Smad4, which functions as a partner of
      receptor-phosphorylated Smad2/3, is required for all of these responses. These
      results define a FoxO-Smad synexpression group or group of genes that are jointly
      induced by a common mechanism in response to TGF-beta. In addition to p15INK4b
      and p21CIP1, these genes include mediators of stress responses (GADD45A, GADD45B,
      and IER1) and adaptive cell signaling responses (CTGF, JAG1, LEMD3, SGK,
      CDC42EP3, and OVOL1). Bioinformatic analysis of the promoter region of these
      genes reveals diverse configurations of Smad and FoxO binding elements, implying
      differences in the regulatory properties of this group of genes. Indeed, a subset
      of FoxO/Smad-dependent TGF-beta gene responses additionally require the
      transcription factor CCAAT/enhancer-binding protein beta. The composition of the
      FoxO-Smad synexpression group suggests that stress reactions and adaptive
      functions accompany the cytostatic response of keratinocytes to TGF-beta.

PMID- 16908842
TI  - Binding of internalized receptors to the PDZ domain of GIPC/synectin recruits
      myosin VI to endocytic vesicles.
AB  - Myosin VI (myo6) is the only actin-based molecular motor that translocates along
      actin filaments toward the minus end. Myo6 participates in two steps of endocytic
      trafficking; it is recruited to both clathrin-coated pits and to ensuing uncoated
      endocytic vesicles (UCV). Although there is evidence suggesting that the PDZ
      adaptor protein GIPC/synectin is involved in the association of myo6 with UCV,
      the recruitment mechanism is unknown. We show that GIPC/synectin is required for
      both internalization of cell surface receptors and for coupling of myo6 to UCV.
      This coupling occurs via a mechanism wherein engagement of the GIPC/synectin PDZ
      domain by C termini of internalized receptors facilitates in trans myo6 binding
      to the GIPC/synectin C terminus located outside of the PDZ domain. Analysis of
      megalin, a prototypical GIPC/synectin-binding receptor, revealed that deletion of
      its PDZ-binding motif drastically reduced GIPC/synectin and myo6 recruitment to
      UCV. Furthermore, interaction with GIPC/synectin was required for megalin's
      function, as megalin was mistargeted in the renal proximal tubules of
      GIPC/synectin-null mice and these mice exhibited proteinuria, a condition
      consistent with defective megalin trafficking.

PMID- 16908843
TI  - T cell surface redox levels determine T cell reactivity and arthritis
      susceptibility.
AB  - Rats and mice with a lower capacity to produce reactive oxygen species (ROS)
      because of allelic polymorphisms in the Ncf1 gene (which encodes neutrophil
      cytosolic factor 1) are more susceptible to develop severe arthritis. These data
      suggest that ROS are involved in regulating the immune response. We now show that
      the lower capacity to produce ROS is associated with an increased number of
      reduced thiol groups (-SH) on T cell membrane surfaces. Artificially increasing
      the number of reduced thiols on T cells from animals with arthritis-protective
      Ncf1 alleles by glutathione treatment lowered the threshold for T cell reactivity
      and enhanced proliferative responses in vitro and in vivo. Importantly, T cells
      from immunized congenic rats with an E3-derived Ncf1 allele (DA.Ncf1E3 rats) that
      cannot transfer arthritis to rats with an arthritis-associated Dark Agouti (DA)
      derived mutated Ncf1 allele (DA.Ncf1DA rats) became arthritogenic after
      increasing cell surface thiol levels. This finding was confirmed by the reverse
      experiment, in which oxidized T cells from DA.Ncf1DA rats induced less severe
      arthritis compared with controls. Therefore, we conclude that ROS production as
      controlled by Ncf1 is important in regulating surface redox levels of T cells and
      thereby suppresses autoreactivity and arthritis development.

PMID- 16908844
TI  - Comprehensive identification of Drosophila dorsal-ventral patterning genes using
      a whole-genome tiling array.
AB  - Dorsal-ventral (DV) patterning of the Drosophila embryo is initiated by Dorsal, a
      sequence-specific transcription factor distributed in a broad nuclear gradient in
      the precellular embryo. Previous studies have identified as many as 70 protein
      coding genes and one microRNA (miRNA) gene that are directly or indirectly
      regulated by this gradient. A gene regulation network, or circuit diagram,
      including the functional interconnections among 40 Dorsal target genes and 20
      associated tissue-specific enhancers, has been determined for the initial stages
      of gastrulation. Here, we attempt to extend this analysis by identifying
      additional DV patterning genes using a recently developed whole-genome tiling
      array. This analysis led to the identification of another 30 protein-coding
      genes, including the Drosophila homolog of Idax, an inhibitor of Wnt signaling.
      In addition, remote 5' exons were identified for at least 10 of the approximately
      100 protein-coding genes that were missed in earlier annotations. As many as nine
      intergenic uncharacterized transcription units were identified, including two
      that contain known microRNAs, miR-1 and -9a. We discuss the potential functions
      of these recently identified genes and suggest that intronic enhancers are a
      common feature of the DV gene network.

PMID- 16908845
TI  - Dystroglycan down-regulation links EGF receptor signaling and anterior-posterior
      polarity formation in the Drosophila oocyte.
AB  - Anterior-posterior axis formation in the Drosophila oocyte requires activation of
      the EGF receptor (EGFR) pathway in the posterior follicle cells (PFC), where it
      also redirects them from the default anterior to the posterior cell fate. The
      relationship between EGFR activity in the PFC and oocyte polarity is unclear,
      because no EGFR-induced changes in the PFC have been observed that subsequently
      affect oocyte polarity. Here, we show that an extracellular matrix receptor,
      Dystroglycan, is down-regulated in the PFC by EGFR signaling, and this down
      regulation is necessary for proper localization of posterior polarity
      determinants in the oocyte. Failure to down-regulate Dystroglycan disrupts
      apicobasal polarity in the PFC, which includes mislocalization of the
      extracellular matrix component Laminin. Our data indicate that Dystroglycan links
      EGFR-induced repression of the anterior follicle cell fate and anterior-posterior
      polarity formation in the oocyte.

PMID- 16908846
TI  - Migratory shearwaters integrate oceanic resources across the Pacific Ocean in an
      endless summer.
AB  - Electronic tracking tags have revolutionized our understanding of broad-scale
      movements and habitat use of highly mobile marine animals, but a large gap in our
      knowledge still remains for a wide range of small species. Here, we report the
      extraordinary transequatorial postbreeding migrations of a small seabird, the
      sooty shearwater, obtained with miniature archival tags that log data for
      estimating position, dive depth, and ambient temperature. Tracks (262+/-23 days)
      reveal that shearwaters fly across the entire Pacific Ocean in a figure-eight
      pattern while traveling 64,037+/-9,779 km roundtrip, the longest animal migration
      ever recorded electronically. Each shearwater made a prolonged stopover in one of
      three discrete regions off Japan, Alaska, or California before returning to New
      Zealand through a relatively narrow corridor in the central Pacific Ocean.
      Transit rates as high as 910+/-186 km.day-1 were recorded, and shearwaters
      accessed prey resources in both the Northern and Southern Hemisphere's most
      productive waters from the surface to 68.2 m depth. Our results indicate that
      sooty shearwaters integrate oceanic resources throughout the Pacific Basin on a
      yearly scale. Sooty shearwater populations today are declining, and because they
      operate on a global scale, they may serve as an important indicator of climate
      change and ocean health.

PMID- 16908847
TI  - Estrogen receptor signaling protects against immune suppression by UV radiation
      exposure.
AB  - The phytoestrogenic isoflavonoid equol is known to protect against solar
      simulated UV radiation-induced inflammation, immunosuppression, and skin
      carcinogenesis. The mechanism may involve antioxidant actions, because equol not
      only is a radical scavenger but also enhances the induction of a relevant
      cutaneous antioxidant, metallothionein. However, this study in female hairless
      mice examined whether the estrogenicity of the isoflavonoid might be responsible.
      Protection by topically applied equol against photoimmune suppression was found
      to be strongly and dose-dependently inhibited by the estrogen receptor (ER)
      antagonist ICI 182,780. Furthermore, ICI 182,780 alone was found to significantly
      exacerbate immunosuppression resulting from solar-simulated UV radiation
      irradiation, suggesting a natural role for the ER in photoimmune protection. In
      support of this role, topical application of the physiological ligand 17-beta
      estradiol also provided dose-dependent photoimmune protection, inhibitable by ICI
      182,780, that was attributed largely to the inactivation of the downstream
      actions of cis-urocanic acid, an important endogenous immunosuppressive
      photoproduct. Thus, a hitherto unrecognized function of the ER as a normal
      photoprotective immune regulator in the skin was revealed. The relationship
      between equol and cutaneous metallothionein suggests an association of the ER
      with this inducible antioxidant in constraining the photoimmune-suppressed state
      and therefore in the prevention of the facilitation of photocarcinogenesis by
      this immunological defect. This role for the ER may underlie important gender
      specific differences in UV-responsiveness that would reflect different needs for
      environmental photoprotection in males and females.

PMID- 16908848
TI  - Unique self-palmitoylation activity of the transport protein particle component
      Bet3: a mechanism required for protein stability.
AB  - Bet3 is a component of the transport protein particle complex involved in
      vesicular trafficking to and through the Golgi complex. X-ray structural analysis
      of human and mouse Bet3 revealed a hydrophobic tunnel inside the protein, which
      is occupied by a fatty acid linked to cysteine-68. We show here that Bet3 has
      strong self-palmitoylating activity. Incubation of purified Bet3 with
      [3H]palmitoyl-CoA (Pal-CoA) leads to a rapid and stoichiometric attachment of
      fatty acids to cysteine-68. Bet3 has an intrinsic affinity for Pal-CoA, and the
      palmitoylation reaction occurs at physiological pH values and Pal-CoA
      concentrations. Moreover, Bet3 is also efficiently palmitoylated at cysteine-68
      inside vertebrate cells. Palmitoylation can occur late after Bet3 synthesis, but
      once the fatty acids are bound they are not removed, not even by disassembly of
      the Golgi complex. Narrowing the hydrophobic tunnel by exchange of alanine-82
      with bulkier amino acids inhibits palmitoylation, both in vitro and inside cells,
      indicating that the fatty acid must insert into the tunnel for stable attachment.
      Finally, we show that palmitoylation of Bet3 plays a structural role. CD
      spectroscopy reveals that chemically deacylated Bet3 has a reduced melting
      temperature. As a consequence of its structural defect nonacylated Bet3 does not
      bind to TPC6, a further subunit of the transport protein particle complex, and is
      degraded inside cells.

PMID- 16908849
TI  - The E3 ubiquitin ligase Itch controls the protein stability of p63.
AB  - p63, a member of the p53 family of transcription factors, plays an important role
      in epithelial development, regulating both cell cycle and apoptosis. Even though
      p63 activity is regulated mainly at the posttranslational level, the control of
      p63 protein stability is far from being fully understood. Here, we show that the
      Hect (homologous to the E6-associated protein C terminus)-containing Nedd4-like
      ubiquitin protein ligase Itch binds, ubiquitylates, and promotes the degradation
      of p63. The physical interaction occurs at the border between the PY and the SAM
      (sterile alpha motif) domains; a single Y504F mutation significantly affects p63
      degradation. Itch and p63 are coexpressed in the epidermis and in primary
      keratinocytes where Itch controls the p63 protein steady-state level.
      Accordingly, p63 protein levels are significantly increased in Itch knockout
      keratinocytes. These data suggest that Itch has a fundamental role in the
      mechanism that controls endogenous p63 protein levels and therefore contributes
      to regulation of p63 in physiological conditions.

PMID- 16908850
TI  - Anisotropic deformation response of single protein molecules.
AB  - Single-molecule methods have given experimental access to the mechanical
      properties of single protein molecules. So far, access has been limited to mostly
      one spatial direction of force application. Here, we report single-molecule
      experiments that explore the mechanical properties of a folded protein structure
      in precisely controlled directions by applying force to selected amino acid
      pairs. We investigated the deformation response of GFP in five selected
      directions. We found fracture forces widely varying from 100 pN up to 600 pN. We
      show that straining the GFP structure in one of the five directions induces
      partial fracture of the protein into a half-folded intermediate structure. From
      potential widths we estimated directional spring constants of the GFP structure
      and found values ranging from 1 N/m up to 17 N/m. Our results show that classical
      continuum mechanics and simple mechanistic models fail to describe the complex
      mechanics of the GFP protein structure and offer insights into the mechanical
      design of protein materials.

PMID- 16908851
TI  - p38MAPK inhibition prevents disease in pemphigus vulgaris mice.
AB  - Pemphigus vulgaris (PV) is a life-threatening autoimmune blistering skin disease
      characterized by detachment of keratinocytes (acantholysis). It has been proposed
      that PV IgG might trigger signaling and that this process may lead to
      acantholysis. Indeed, we recently identified a rapid and dose-dependent
      phosphorylation of p38 mitogen-activated protein kinase (p38MAPK) and heat shock
      protein (HSP) 27 after binding of PV antibodies to cultured keratinocytes. In
      human keratinocyte cultures, inhibitors of p38MAPK prevented PV IgG-induced
      phosphorylation of HSP27 and, more importantly, prevented the early cytoskeletal
      changes associated with loss of cell-cell adhesion. This study was undertaken to
      (i) determine whether p38MAPK and HSP25, the murine HSP27 homolog, were similarly
      phosphorylated in an in vivo model of PV and (ii) investigate the potential
      therapeutic use of p38MAPK inhibition to block blister formation in an animal
      model of PV. We now report that p38MAPK inhibitors prevented PV blistering
      disease in vivo. Targeting the end-organ by inhibiting keratinocyte desmosome
      signaling may be effective for treating desmosome autoimmune blistering
      disorders.

PMID- 16908852
TI  - C-H bond activation through steric crowding of normally inert ligands in the
      sterically crowded gadolinium and yttrium (C5Me5)3M complexes.
AB  - Synthesis of the sterically crowded Tris(pentamethylcyclopentadienyl) lanthanide
      complexes, (C5Me5)3Ln, has demonstrated that organometallic complexes with
      unconventionally long metal ligand bond lengths can be isolated that provide
      options to develop new types of ligand reactivity based on steric crowding.
      Previously, the (C5Me5)3M complexes were known only with the larger lanthanides,
      La-Sm. The synthesis of even more crowded complexes of the smaller metals Gd and
      Y is reported here. These complexes allow an evaluation of the size/reactivity
      correlations previously limited to the larger metals and demonstrate a previously
      undescribed type of C5Me5-based reaction, namely C-H bond activation. (C5Me5)3Gd,
      was prepared from GdCl3 through (C5Me5)2GdCl2K(THF)2, (C5Me5)2Gd(C3H5), and
      [(C5Me5)2Gd][BPh4] and structurally characterized by x-ray crystallography.
      Although Gd3+ is redox-inactive, (C5Me5)3Gd functions as a reducing agent in
      reactions with 1,3,5,7-cyclooctatetraene (COT) and triphenylphosphine selenide to
      make (C5Me5)Gd(C8H8), [(C5Me5)2Gd]2Se2, and [(C5Me5)2Gd]2Se depending on the
      stoichiometry used. When the analogous synthetic method was attempted with
      yttrium in arene solvents, the previously characterized (C5Me5)2YR complexes
      (R=C6H5, CH2C6H5) were isolated instead, i.e., C-H bond activation of solvent
      occurred. To avoid this problem, (C5Me5)3Y was synthesized in high yield from
      [(C5Me5)2YH]2 and tetramethylfulvene in aliphatic solvents. Isolated (C5Me5)3Y
      was found to metalate benzene and toluene with concomitant formation of C5Me5H, a
      reaction contrary to the normal pKa values of these hydrocarbons. In this case,
      the normally inert (C5Me5)1- ligand engages in C-H bond activation due to the
      extreme steric crowding.

PMID- 16908853
TI  - Deletion of TolC orthologs in Francisella tularensis identifies roles in
      multidrug resistance and virulence.
AB  - The Gram-negative bacterium Francisella tularensis is the causative agent of
      tularemia. Interest in this zoonotic pathogen has increased due to its
      classification as a category A agent of bioterrorism, but little is known about
      the molecular mechanisms underlying its virulence, and especially what secretion
      systems and virulence factors are present. In this study, we characterized two
      genes in the F. tularensis genome, tolC and a gene we term ftlC, whose products
      have high homology with the Escherichia coli TolC protein. TolC functions as the
      outer membrane channel component for both type I secretion and multidrug efflux
      systems. We constructed deletion mutations of these genes in the F. tularensis
      live vaccine strain by allelic replacement. Deletion of either tolC or ftlC
      caused increased sensitivity to various antibiotics, detergents, and dyes,
      indicating both genes are involved in the multidrug resistance machinery of F.
      tularensis. Complementation of the deletion mutations in trans restored drug
      resistance. Neither tolC nor ftlC was required for replication of the live
      vaccine strain in murine bone marrow-derived macrophages. However, deletion of
      tolC, but not ftlC, caused a significant attenuation of virulence in a mouse
      model of tularemia that could be complemented by addition of tolC in trans. Thus,
      tolC is a critical virulence factor of F. tularensis in addition to its role in
      multidrug resistance, which suggests the presence of a functional type I
      secretion system.

PMID- 16908854
TI  - Sequestering carbon dioxide into complex structures of naturally occurring gas
      hydrates.
AB  - Large amounts of CH4 in the form of solid hydrates are stored on continental
      margins and in permafrost regions. If these CH4 hydrates could be converted into
      CO2 hydrates, they would serve double duty as CH4 sources and CO2 storage sites.
      We explore here the swapping phenomenon occurring in structure I (sI) and
      structure II (sII) CH4 hydrate deposits through spectroscopic analyses and its
      potential application to CO2 sequestration at the preliminary phase. The present
      85% CH4 recovery rate in sI CH4 hydrate achieved by the direct use of binary
      N2+CO2 guests is surprising when compared with the rate of 64% for a pure CO2
      guest attained in the previous approach. The direct use of a mixture of N2+CO2
      eliminates the requirement of a CO2 separation/purification process. In addition,
      the simultaneously occurring dual mechanism of CO2 sequestration and CH4 recovery
      is expected to provide the physicochemical background required for developing a
      promising large-scale approach with economic feasibility. In the case of sII CH4
      hydrates, we observe a spontaneous structure transition of sII to sI during the
      replacement and a cage-specific distribution of guest molecules. A significant
      change of the lattice dimension caused by structure transformation induces a
      relative number of small cage sites to reduce, resulting in the considerable
      increase of CH4 recovery rate. The mutually interactive pattern of targeted guest
      cage conjugates possesses important implications for the diverse hydrate-based
      inclusion phenomena as illustrated in the swapping process between CO2 stream and
      complex CH4 hydrate structure.

PMID- 16908855
TI  - Autogenous and nonautogenous control of response in a genetic network.
AB  - Feedback-based control methods determine the behavior of cellular systems, an
      example being autogenous control, the regulation of production of a protein by
      itself. This control strategy was theoretically shown to be superior to an
      equivalent but nonautogenously regulated system when based on a repressor.
      Although some of its advantages were later confirmed with isolated synthetic
      circuits, the superiority of autogenous control in natural networks remains
      untested. Here, we use the SOS DNA repair system of Escherichia coli, where
      autogenous control is part of a single-input module, as a valid model to evaluate
      the functional advantages and biological implications of this mechanism. We
      redesign the control of its master regulator, the protein LexA, so that it
      becomes nonautogenously controlled. We compare both systems by combining high
      resolution expression measurements with mathematical modeling. We show that the
      stronger stability associated with the autogenous regulation prevents false
      triggering of the response due to transient fluctuations in the inducing signal
      and that this control also reduces the system recovery time at low DNA damage.
      Likewise, autoregulation produces responses proportional to the damage signal
      level. In contrast, bacteria with LexA constitutively expressed induce maximal
      action even for very low damage levels. This excess in response comes at a cost,
      because it reduces comparatively the growth rate of these cells. Our results
      suggest that autogenous control evolved as a strategy to optimally respond to
      multiple levels of input signal minimizing the costs of the response and
      highlights reasons why master regulators of single-input modules are mostly
      autorepressed.

PMID- 16908856
TI  - Efficient generation of retinal progenitor cells from human embryonic stem cells.
AB  - The retina is subject to degenerative conditions, leading to blindness. Although
      retinal regeneration is robust in lower vertebrates, regeneration does not occur
      in the adult mammalian retina. Thus, we have developed efficient methods for
      deriving retinal neurons from human embryonic stem (hES) cells. Under appropriate
      culture conditions, up to 80% of the H1 line can be directed to the retinal
      progenitor fate, and express a gene expression profile similar to progenitors
      derived from human fetal retina. The hES cell-derived progenitors differentiate
      primarily into inner retinal neurons (ganglion and amacrine cells), with
      functional glutamate receptors. Upon coculture with retinas derived from a mouse
      model of retinal degeneration, the hES cell derived retinal progenitors integrate
      with the degenerated mouse retina and increase in their expression of
      photoreceptor-specific markers. These results demonstrate that human ES cells can
      be selectively directed to a neural retinal cell fate and thus may be useful in
      the treatment of retinal degenerations.

PMID- 16908857
TI  - Local peptide movement in the photoreaction intermediate of rhodopsin.
AB  - Photoactivation of the visual rhodopsin, a prototypical G protein-coupled
      receptor (GPCR), involves efficient conversion of the intrinsic inverse-agonist
      11-cis-retinal to the all-trans agonist. This event leads to the rearrangement of
      the heptahelical transmembrane bundle, which is thought to be shared by hundreds
      of GPCRs. To examine this activation mechanism, we determined the x-ray
      crystallographic model of the photoreaction intermediate of rhodopsin,
      lumirhodopsin, which represents the conformational state having the nearly
      complete all-trans agonist form of the retinal. A difference electron density map
      clearly indicated that the distorted all-trans-retinal in the precedent
      intermediate bathorhodopsin relaxes by dislocation of the beta-ionone ring in
      lumirhodopsin, along with significant peptide displacement in the middle of helix
      III, including approximately two helical turns. This local movement results in
      the breaking of the electrostatic interhelical restraints mediated by many of the
      conserved residues among rhodopsin-like GPCRs, with consequent acquisition of
      full activity.

PMID- 16908858
TI  - Inhibition of human T cell leukemia virus type 2 replication by the suppressive
      action of class II transactivator and nuclear factor Y.
AB  - The master regulator of MHC-II gene transcription, class II transactivator
      (CIITA), acts as a potent inhibitor of human T cell leukemia virus type 2 (HTLV
      2) replication by blocking the activity of the viral Tax-2 transactivator. Here,
      we show that this inhibitory effect takes place at the nuclear level and maps to
      the N-terminal 1-321 region of CIITA, where we identified a minimal domain, from
      positions 64-144, that is strictly required to suppress Tax-2 function.
      Furthermore, we show that Tax-2 specifically cooperates with cAMP response
      element binding protein-binding protein (CBP) and p300, but not with p300/CBP
      associated factor, to enhance transcription from the viral promoter. This finding
      represents a unique difference with respect to Tax-1, which uses all three
      coactivators to transactivate the human T cell leukemia virus type 1 LTR. Direct
      sequestering of CBP or p300 is not the primary mechanism by which CIITA causes
      suppression of Tax-2. Interestingly, we found that the transcription factor
      nuclear factor Y, which interacts with CIITA to increase transcription of MHC-II
      genes, exerts a negative regulatory action on the Tax-2-mediated HTLV-2 LTR
      transactivation. Thus, CIITA may inhibit Tax-2 function, at least in part,
      through nuclear factor Y. These findings demonstrate the dual defensive role of
      CIITA against pathogens: it increases the antigen-presenting function for viral
      determinants and suppresses HTLV-2 replication in infected cells.

PMID- 16908859
TI  - Binaural and cochlear disparities.
AB  - Binaural auditory neurons exhibit "best delays" (BDs): They are maximally
      activated at certain acoustic delays between sounds at the two ears and thereby
      signal spatial sound location. BDs arise from delays internal to the auditory
      system, but their source is controversial. According to the classic Jeffress
      model, they reflect pure time delays generated by differences in axonal length
      between the inputs from the two ears to binaural neurons. However, a relationship
      has been reported between BDs and the frequency to which binaural neurons are
      most sensitive (the characteristic frequency), and this relationship is not
      predicted by the Jeffress model. An alternative hypothesis proposes that binaural
      neurons derive their input from slightly different places along the two cochleas,
      which induces BDs by virtue of the slowness of the cochlear traveling wave. To
      test this hypothesis, we performed a coincidence analysis on spiketrains of pairs
      of auditory nerve fibers originating from different cochlear locations. In
      effect, this analysis mimics the processing of phase-locked inputs from each ear
      by binaural neurons. We find that auditory nerve fibers that innervate different
      cochlear sites show a maximum number of coincidences when they are delayed
      relative to each other, and that the optimum delays decrease with characteristic
      frequency as in binaural neurons. These findings suggest that cochlear
      disparities make an important contribution to the internal delays observed in
      binaural neurons.

PMID- 16908861
TI  - Evidence from meimechites and other low-degree mantle melts for redox controls on
      mantle-crust fractionation of platinum-group elements.
AB  - Understanding of the geochemistry of the chalcophile elements [i.e., Os, Ir, Ru,
      Pt, Pd (platinum-group elements), and Au, Cu, Ni] has been informed for at least
      20 years by the common assumption that when crust-forming partial melts are
      extracted from the upper mantle, sulfide liquid in the restite sequesters
      chalcophile elements until the extent of partial melting exceeds approximately
      25% and all of the sulfide has been dissolved in silicate melt [Hamlyn, P. R. &
      Keays, R. R. (1985) Geochim. Cosmochim. Acta 49, 1797-1811]. Here we document
      very high, unfractionated, chalcophile element concentrations in small-degree
      partial melts from the mantle that cannot be reconciled with the canonical
      residual sulfide assumption. We show that the observed high, unfractionated
      platinum-group element concentrations in small-degree partial melts can be
      attained if the melting takes place at moderately high oxygen fugacity, which
      will reduce the amount of sulfide due to the formation of sulfate and will also
      destabilize residual monosulfide solid solution by driving sulfide melts into the
      spinel-liquid divariant field. Magmas formed at high oxygen fugacity by small
      degrees of mantle melting can be important agents for the transfer of chalcophile
      elements from the upper mantle to the crust and may be progenitors of significant
      ore deposits of Pt, Pd, and Au.

PMID- 16908860
TI  - NO synthase 2 (NOS2) deletion promotes multiple pathologies in a mouse model of
      Alzheimer's disease.
AB  - Alzheimer's disease is characterized by two primary pathological features:
      amyloid plaques and neurofibrillary tangles. The interconnection between amyloid
      and tau aggregates is of intense interest, but mouse models have yet to reveal a
      direct interrelationship. We now show that NO may be a key factor that connects
      amyloid and tau pathologies. Genetic removal of NO synthase 2 in mice expressing
      mutated amyloid precursor protein results in pathological hyperphosphorylation of
      mouse tau, its redistribution to the somatodendritic compartment in cortical and
      hippocampal neurons, and aggregate formation. Lack of NO synthase 2 in the
      amyloid precursor protein Swedish mutant mouse increased insoluble beta-amyloid
      peptide levels, neuronal degeneration, caspase-3 activation, and tau cleavage,
      suggesting that NO acts at a junction point between beta-amyloid peptides,
      caspase activation, and tau aggregation.

PMID- 16908862
TI  - Climate variability has a stabilizing effect on the coexistence of prairie
      grasses.
AB  - How expected increases in climate variability will affect species diversity
      depends on the role of such variability in regulating the coexistence of
      competing species. Despite theory linking temporal environmental fluctuations
      with the maintenance of diversity, the importance of climate variability for
      stabilizing coexistence remains unknown because of a lack of appropriate long
      term observations. Here, we analyze three decades of demographic data from a
      Kansas prairie to demonstrate that interannual climate variability promotes the
      coexistence of three common grass species. Specifically, we show that (i) the
      dynamics of the three species satisfy all requirements of "storage effect" theory
      based on recruitment variability with overlapping generations, (ii) climate
      variables are correlated with interannual variation in species performance, and
      (iii) temporal variability increases low-density growth rates, buffering these
      species against competitive exclusion. Given that environmental fluctuations are
      ubiquitous in natural systems, our results suggest that coexistence based on the
      storage effect may be underappreciated and could provide an important alternative
      to recent neutral theories of diversity. Field evidence for positive effects of
      variability on coexistence also emphasizes the need to consider changes in both
      climate means and variances when forecasting the effects of global change on
      species diversity.

PMID- 16908863
TI  - TNFalpha mediates the skeletal effects of thyroid-stimulating hormone.
AB  - We have shown recently that by acting on the thyroid-stimulating hormone (TSH)
      receptor (TSHR), TSH negatively regulates osteoclast differentiation. Both
      heterozygotic and homozygotic TSHR null mice are osteopenic with evidence of
      enhanced osteoclast differentiation. Here, we report that the accompanying
      elevation of TNFalpha, an osteoclastogenic cytokine, causes the increased
      osteoclast differentiation. This enhancement in TSHR-/- and TSHR+/- mice is
      abrogated in compound TSHR-/-/TNFalpha-/- and TSHR+/-/TNFalpha+/- mice,
      respectively. In parallel studies, we find that TSH directly inhibits TNFalpha
      production, reduces the number of TNFalpha-producing osteoclast precursors, and
      attenuates the induction of TNFalpha expression by IL-1, TNFalpha, and receptor
      activator of NF-kappaB ligand. TSH also suppresses osteoclast formation in murine
      macrophages and RAW-C3 cells. The suppression is more profound in cells that
      overexpress the TSHR than those transfected with empty vector. The overexpression
      of ligand-independent, constitutively active TSHR abrogates osteoclast formation
      even under basal conditions and in the absence of TSH. Finally, IL-1/TNFalpha and
      receptor activator of NF-kappaB ligand fail to stimulate AP-1 and NF-kappaB
      binding to DNA in cells transfected with TSHR or constitutively active TSHR. The
      results suggest that TNFalpha is the critical cytokine mediating the downstream
      antiresorptive effects of TSH on the skeleton.

PMID- 16908864
TI  - Oncogenic Kit signaling and therapeutic intervention in a mouse model of
      gastrointestinal stromal tumor.
AB  - Kit receptor-activating mutations are critical in the pathogenesis of
      gastrointestinal stromal tumors (GIST). We investigated mechanisms of oncogenic
      Kit signaling and the consequences of therapeutic intervention in a mouse model
      of human GIST. Treatment of GIST mice with imatinib decreased cell proliferation
      and increased apoptosis in the tumor. Analysis of tumor tissue from imatinib
      treated mice showed diminished phosphatidylinositol 3-kinase (PI3-kinase) and
      mammalian target of rapamycin (mTOR) signaling suggesting that oncogenic Kit
      signaling critically contributes to the translational response in GIST. Treatment
      with RAD001 (everolimus), an mTOR inhibitor, diminished the translational
      response and cell proliferation in tumor lesions, pointing to mTOR inhibition as
      a therapeutic approach for imatinib-resistant GIST. Analysis of RNA expression
      profiles in GIST lesions with and without imatinib treatment showed changes in
      expression of IFN-inducible genes and cell cycle regulators. These results
      convincingly show that KitV558Delta/+ mice represent a unique faithful mouse
      model of human familial GIST, and they demonstrate the utility of these mice for
      preclinical investigations and to elucidate oncogenic signaling mechanisms by
      using genetic approaches and targeted pharmacological intervention.

PMID- 16908865
TI  - Differential regulation of phagosome maturation in macrophages and dendritic
      cells mediated by Rho GTPases and ezrin-radixin-moesin (ERM) proteins.
AB  - Deletion of apoptotic cells from tissues involves their phagocytosis by
      macrophages, dendritic cells, and tissue cells. Although much attention has been
      focused on the participating ligands, receptors, and mechanisms of uptake, little
      is known of the disposition of the ingested cell within the phagosome. Here we
      show that uptake of apoptotic cells by macrophages or fibroblasts results in
      rapid phagosome maturation, whereas macrophage phagosomes containing Ig-opsonized
      target cells mature at a slower rate. The early maturation was shown to depend on
      activation of Rho acting through Rho kinase on ezrin-radixin-moesin proteins.
      Blockade of Rho signaling or inhibition of moesin both delayed maturation rates
      to those seen with opsonized targets. By contrast, phagosome maturation in
      dendritic cells was slower, similar between apoptotic and opsonized target cells,
      and unaffected by Rho inhibition. These observations have direct implications for
      the clearance of dying cells and the roles played by different phagocytes in
      antigen digestion and presentation.

PMID- 16908866
TI  - Dosing schedules of 6-month regimens and relapse for pulmonary tuberculosis.
AB  - RATIONALE: The optimal approach for reducing tuberculosis relapse is open.
      OBJECTIVES: We examined the possibility of reducing relapse by increasing dosing
      schedules. METHODS: We conducted a systematic review of published clinical trials
      involving adult cohorts with pulmonary tuberculosis treated using 6-mo rifamycin
      containing regimens, which were grouped under seven categories ordered by dosing
      schedules. Assuming cavitation and positive 2-mo culture were the driving forces
      for relapse, a static deterministic model apportioned observed numbers with and
      without relapse in each cohort into eight subgroups. Combining subgroups
      stratified by cavitation, 2-mo culture, and regimens enabled estimation of
      adjusted relapse risks. chi2 Tests for trend and logistic regression analysis
      examined the relationship between relapse and dosing schedules. RESULTS: We
      identified 200 cases of bacteriologic relapse out of 5,208 patients in 32
      cohorts. A logistic risk model showed a significant dose-response relationship
      between dosing schedules and relapse, with the following odds (95% confidence
      intervals) of relapse relative to daily regimens: 1.6 (0.6-4.1) for daily initial
      phase (IP) plus thrice-weekly continuation phase (CP), 2.8 (1.3-6.1) for daily IP
      plus twice-weekly CP, 2.8 (1.4-5.7) for thrice-weekly, 5.0 (2.4-10.5) for daily
      IP plus once-weekly rifapentine, and 7.1 (3.3-15.3) for thrice-weekly IP plus
      once-weekly rifapentine. In the presence of cavitation, only 6-mo daily or daily
      IP plus thrice-weekly CP attained best-estimated relapse risks below 5%; they
      reached 6% when 2-mo culture was also positive. CONCLUSIONS: Cavitary
      tuberculosis is best treated with 6-mo regimens comprising daily IP and thrice
      weekly CP, which may be extended when 2-mo culture is positive.

PMID- 16908867
TI  - Caspase-1 regulates Escherichia coli sepsis and splenic B cell apoptosis
      independently of interleukin-1beta and interleukin-18.
AB  - RATIONALE: Caspase-1 processes interleukin 1beta (IL-1beta) and IL-18 but may
      also contribute to apoptosis. In this context, caspase-1 knockout mice have been
      shown to be protected from endotoxin-induced mortality, whereas IL-1beta knockout
      mice are not protected. OBJECTIVES: We therefore sought to delineate the
      mechanisms responsible for the differential responses between caspase-1 and IL
      1beta knockout mice. METHODS: Caspase-1 knockout, IL-1beta knockout, and IL
      1beta/IL-18 double knockout mice were compared with wild-type mice for survival
      after intraperitoneal challenge with live Escherichia coli. MEASUREMENTS AND MAIN
      RESULTS: Caspase-1 knockout animals were protected from bacterial challenge,
      whereas wild-type, IL-1beta knockout, and IL-1beta/IL-18 double knockout animals
      were not. Wild-type animals and both IL-1beta knockout and IL-1beta/IL-18 double
      knockout mice demonstrated significant splenic B lymphocyte apoptosis, which was
      absent in the caspase-1 knockout mice. Importantly, IL-1beta/IL-18 double
      knockout mice were protected from splenic cell apoptosis and sepsis-induced
      mortality by the caspase inhibitor zVAD-fmk. Furthermore, wild-type but not
      caspase-1 knockout splenic B lymphocytes induced peritoneal macrophages to assume
      an inhibitory phenotype. CONCLUSION: Taken together, these findings suggest that
      caspase-1 is important in the host response to sepsis at least in part via its
      ability to regulate sepsis-induced splenic cell apoptosis.

PMID- 16908869
TI  - Age-related variability in cortical activity during language processing.
AB  - PURPOSE: The present study investigated the extent of cortical activity during
      overt picture naming using functional magnetic resonance imaging (fMRI). METHOD:
      Participants comprised 20 healthy, adult participants with ages ranging from 20
      to 82 years. While undergoing fMRI, participants completed a picture-naming task
      consisting of 60 high-frequency nouns. RESULTS: Linear regression analysis
      revealed a positive relationship between age and cortical activation intensity in
      Broca's and Wernicke's areas as well as the right-hemisphere homologue of Broca's
      area. In contrast, neural activity in the anterior cingulate gyrus, an area
      thought to be involved in attentional processing, did not increase as a function
      of age. CONCLUSIONS: These findings suggest age-related increases in cortical
      activation during simple language tasks, such as picture naming, in brain areas
      typically associated with language processing.

PMID- 16908868
TI  - Intrinsic biochemical and functional differences in bronchial epithelial cells of
      children with asthma.
AB  - RATIONALE: Convincing evidence of epithelial damage and aberrant repair exists in
      adult asthmatic airways, even in the absence of inflammation. However, comparable
      studies in children have been limited by access and availability of clinical
      samples. OBJECTIVES: To determine whether bronchial epithelial cells from
      children with asthma are inherently distinct from those obtained from children
      without asthma. METHODS: Epithelial cells were obtained by nonbronchoscopic
      bronchial brushing of children with mild asthma (n = 7), atopic children without
      asthma (n = 9), and healthy children (n = 12). Cells were subject to morphologic,
      biochemical, molecular, and functional assessment. Responses were also compared
      with commercially available epithelial cultures and the transformed cell line
      16HBE140. RESULTS: All epithelial cells exhibited a "cobblestone" morphology,
      which was maintained throughout culture and repeated passage. Expression of
      cytokeratin 19 varied, with disease phenotype being greatest in healthy
      nonatopics and lowest in asthmatics. In contrast, expression of cytokeratin 5/14
      was greatest in asthmatic samples and least in healthy nonatopic samples.
      Asthmatic epithelial cells also spontaneously produced significantly greater
      amounts of interleukin (IL)-6, prostaglandin E2, and epidermal growth factor, and
      equivalent amounts of IL-1beta and soluble intracellular adhesion molecule-1, but
      significantly lower amounts of transforming growth factor beta1. This profile was
      maintained through successive passages. Asthmatic epithelial cells also exhibited
      greater rates of proliferation than nonasthmatic cells. CONCLUSIONS: This study
      has shown that epithelial cells from children with mild asthma are intrinsically
      different both biochemically and functionally compared with epithelial cells from
      children without asthma. Importantly, these differences are maintained over
      successive passages, suggesting that they are not dependent on an in vivo
      environment.

PMID- 16908870
TI  - A randomized comparison of the effect of two prelinguistic communication
      interventions on the acquisition of spoken communication in preschoolers with
      ASD.
AB  - PURPOSE: This randomized group experiment compared the efficacy of 2
      communication interventions (Responsive Education and Prelinguistic Milieu
      Teaching [RPMT] and the Picture Exchange Communication System [PECS]) on spoken
      communication in 36 preschoolers with autism spectrum disorders (ASD). METHOD:
      Each treatment was delivered to children for a maximum total of 24 hr over a 6
      month period. Spoken communication was assessed in a rigorous test of
      generalization at pretreatment, posttreatment, and 6-month follow-up periods.
      RESULTS: PECS was more successful than RPMT in increasing the number of
      nonimitative spoken communication acts and the number of different nonimitative
      words used at the posttreatment period. Considering growth over all 3 measurement
      periods, an exploratory analysis showed that growth rate of the number of
      different nonimitative words was faster in the PECS group than in the RPMT group
      for children who began treatment with relatively high object exploration. In
      contrast, analogous slopes were steeper in the RPMT group than in the PECS group
      for children who began treatment with relatively low object exploration.

PMID- 16908871
TI  - Response time in 14-year-olds with language impairment.
AB  - PURPOSE: To determine whether children with language impairment were slower than
      typically developing peers at age 14, and whether slowing, if present, was
      similar across task domains; whether differences in response time (RT) across
      domains were the same for children with specific language impairment (SLI) and
      nonspecific language impairment (NLI); and whether RT performance at age 9
      predicted performance at age 14. METHOD: Fourteen-year-old children with SLI (n =
      20), NLI (n = 15), and typical development (NLD; n = 31) were administered
      several linguistic and nonlinguistic speeded tasks. The children had received the
      same tasks at age 9. RT performance was examined. RESULTS: Both the SLI and the
      NLI groups were significantly slower than the NLD group in motor, nonverbal
      cognitive, and language task domains, and there was no significant difference
      among domains. Individual analyses showed that most, but not all, children with
      SLI and NLI were slower than the NLD group mean. Slowing at age 9 and age 14 were
      moderately correlated. CONCLUSIONS: The results suggest that slow RT is a
      persistent characteristic of many children with language impairment; however, the
      nature of the relationship between RT and language performance requires further
      investigation.

PMID- 16908872
TI  - Effect of semantic naming treatment on crosslinguistic generalization in
      bilingual aphasia.
AB  - PURPOSE: The effect of semantic naming treatment on crosslinguistic
      generalization was investigated in 3 participants with English-Spanish bilingual
      aphasia. METHOD: A single-subject experimental designed was used. Participants
      received semantic treatment to improve naming of English or Spanish items, while
      generalization was tested to untrained semantically related items in the trained
      language and translations of the trained and untrained items in the untrained
      language. RESULTS: Results demonstrated a within- and across-languages effect on
      generalization related to premorbid language proficiencies. Participant 1 (P1;
      equal premorbid proficiency across languages) showed within-language
      generalization in the trained language (Spanish) as well as crosslinguistic
      generalization to the untrained language (English). Participant 2 (P2) and
      Participant (P3) were more proficient premorbidly in English. With treatment in
      English, P2 showed within-language generalization to semantically related items,
      but no crosslinguistic generalization. With treatment in Spanish, both P2 and P3
      exhibited no within-language generalization, but crosslinguistic generalization
      to English (dominant language) occurred. Error analyses indicated an evolution of
      errors as a consequence of treatment. CONCLUSIONS: These results are preliminary
      because all participants were not treated in both languages. However, the results
      suggest that training the less dominant language may be more beneficial in
      facilitating crosslinguistic generalization than training the more proficient
      language in an unbalanced bilingual individual.

PMID- 16908873
TI  - Tense and agreement morphemes in the speech of children with specific language
      impairment during intervention: phase 2.
AB  - PURPOSE: The goals of this investigation were to determine whether treatment
      assists children with specific language impairment (SLI) in the use of
      grammatical morphemes that mark tense and agreement and whether treatment gains
      influence the children's use of other, untreated morphemes. METHOD: Twenty-five
      children with SLI participated in 96 intervention sessions designed to facilitate
      the children's use of third-person singular -s or auxiliary is/are/was. RESULTS:
      The children showed significantly larger gains on the target forms than on
      control forms (e.g., past tense -ed) that were monitored but not included in
      intervention. Along with possible treatment-related generalization across
      morpheme types, there was also evidence of one morpheme type influencing another
      when neither was the target of intervention. CONCLUSIONS: Although the results
      provide clear evidence for intervention effects, it appeared as if maturational
      factors also played a role. The findings are discussed in terms of their
      implications for treatment and for characterizing development in SLI.

PMID- 16908874
TI  - African American preschoolers' language, emergent literacy skills, and use of
      African American English: a complex relation.
AB  - PURPOSE: This study examined the relation between African American preschoolers'
      use of African American English (AAE) and their language and emergent literacy
      skills in an effort to better understand the perplexing and persistent
      difficulties many African American children experience learning to read
      proficiently. METHOD: African American preschoolers' (n = 63) vocabulary skills
      were assessed in the fall and their language and emergent literacy skills were
      assessed in the spring. The relation between students' AAE use and their
      vocabulary and emergent literacy skills was examined using hierarchical linear
      modeling (HLM), controlling for fall vocabulary and other child, family, and
      school variables. Children's use of AAE was examined across two contexts-sentence
      imitation and oral narrative using a wordless storybook prompt. RESULTS: There
      was a significant -shaped relation between the frequency with which preschoolers
      used AAE features and their language and emergent literacy skills. Students who
      used AAE features with greater or lesser frequency demonstrated stronger sentence
      imitation, letter-word recognition, and phonological awareness skills than did
      preschoolers who used AAE features with moderate frequency, controlling for fall
      vocabulary skills. Fewer preschoolers used AAE features during the sentence
      imitation task with explicit expectations for Standard American English (SAE) or
      School English than they did during an oral narrative elicitation task with
      implicit expectations for SAE. CONCLUSIONS: The nonlinear relation between AAE
      use and language and emergent literacy skills, coupled with systematic
      differences in AAE use across contexts, indicates that some preschoolers may be
      dialect switching between AAE and SAE, suggesting emerging
      pragmatic/metalinguistic awareness.

PMID- 16908875
TI  - Mean length of utterance in children with specific language impairment and in
      younger control children shows concurrent validity and stable and parallel growth
      trajectories.
AB  - PURPOSE: Although mean length of utterance (MLU) is a useful benchmark in studies
      of children with specific language impairment (SLI), some empirical and
      interpretive issues are unresolved. The authors report on 2 studies examining,
      respectively, the concurrent validity and temporal stability of MLU equivalency
      between children with SLI and typically developing children. METHOD: Study 1 used
      124 archival conversational samples consisting of 39 children with SLI (age 5;0
      [years;months]), 40 MLU-equivalent typically developing children (age 3;0), and
      45 age-equivalent controls. Concurrent validity of MLU matches was examined by
      considering the correspondence between MLU and developmental sentence scoring
      (DSS), index of productive syntax (IPSyn), and MLU in words. Study 2 used 205
      archival conversational samples, representing 5 years of longitudinal data
      collected on 20 children with SLI (from age 5;0) and 18 MLU matches (from age
      3;0). Evaluation of growth dimensions within and across groups was carried out
      via growth-curve modeling. RESULTS: In Study 1, high levels of correlation among
      the MLU, DSS, and IPSyn measures were observed. Differences between groups were
      not significant. In Study 2, temporal stability of MLU matches was robust over a
      5 year period. CONCLUSIONS: MLU appears to be a reliable and valid index of
      general language development and an appropriate grouping variable from age 3 to
      10. The developmental stability of MLU matches is indicative of shared underlying
      growth mechanisms.

PMID- 16908876
TI  - Auditory sensitivity and the prelinguistic vocalizations of early-amplified
      infants.
AB  - PURPOSE: Vocalization development has not been studied thoroughly in infants with
      early-identified hearing loss who receive hearing aids in the 1st year of life.
      This study sought to evaluate the relationship between auditory sensitivity and
      prelinguistic vocalization patterns in infants during the babbling stage. METHOD:
      Spontaneous vocalizations of 15 early-identified infants with varying degrees of
      hearing sensitivity, from normal to profound hearing loss, were audiotaped and
      perceptually transcribed. Associations between the infant's unaided pure-tone
      average and the following vocalizations were explored: canonical babbling ratio,
      percentage of utterances containing canonical syllables, canonical syllable
      shapes, number of syllable sequences, and consonant-onset patterns in canonical
      syllables. RESULTS: Hearing sensitivity was significantly associated with the
      percentage of utterances containing canonical syllables, the vocalization types
      used in utterances, and canonical syllable shapes used by the infants.
      CONCLUSIONS: Auditory sensitivity contributes significantly to the emergence of
      babbling patterns. In addition, there is a need for continued study of the
      vocalizations of infants with milder forms of hearing loss, because in this
      study, their vocalizations were highly variable despite having received early
      amplification.

PMID- 16908878
TI  - Visual phonemic ambiguity and speechreading.
AB  - PURPOSE: To study the role of visual perception of phonemes in visual perception
      of sentences and words among normal-hearing individuals. METHOD: Twenty-four
      normal-hearing adults identified consonants, words, and sentences, spoken by
      either a human or a synthetic talker. The synthetic talker was programmed with
      identical parameters within phoneme groups, hypothetically resulting in
      simplified articulation. Proportions of correctly identified phonemes per
      participant, condition, and task, as well as sensitivity to single consonants and
      clusters of consonants, were measured. Groups of mutually exclusive consonants
      were used for sensitivity analyses and hierarchical cluster analyses. RESULTS:
      Consonant identification performance did not differ as a function of talker, nor
      did average sensitivity to single consonants. The bilabial and labiodental
      clusters were most readily identified and cohesive for both talkers. Word and
      sentence identification was better for the human talker than the synthetic
      talker. The participants were more sensitive to the clusters of the least visible
      consonants with the human talker than with the synthetic talker. CONCLUSIONS: It
      is suggested that ability to distinguish between clusters of the least visually
      distinct phonemes is important in speechreading. Specifically, it reduces the
      number of candidates, and thereby facilitates lexical identification.

PMID- 16908877
TI  - Consistency of sentence intelligibility across difficult listening situations.
AB  - PURPOSE: The extent to which a sentence retains its level of spoken
      intelligibility relative to other sentences in a list under a variety of
      difficult listening situations was examined. METHOD: The strength of this
      sentence effect was studied using the Central Institute for the Deaf Everyday
      Speech sentences and both generalizability analysis (Experiments 1 and 2) and
      correlation (Analyses 1 and 2). RESULTS: Experiments 1 and 2 indicated the
      presence of a prominent sentence effect (substantial variance accounted for)
      across a large range of group mean intelligibilities (Experiment 1) and different
      spectral contents (Experiment 2). In Correlation Analysis 1, individual sentence
      scores were found to be correlated across listeners in each group producing
      widely ranging levels of performance. The sentence effect accounted for over half
      of the variance between listener-ability groups. In Correlation Analysis 2,
      correlations accounted for an average of 42% of the variance across a variety of
      listening conditions. However, when the auditory data were compared to speech
      reading data, the cross-modal correlations were quite low. CONCLUSIONS: The
      stability of relative sentence intelligibility (the sentence effect) appears
      across a wide range of mean intelligibilities, across different spectral
      compositions, and across different listener performance levels, but not across
      sensory modalities.

PMID- 16908879
TI  - Correction of the peripheral spatiotemporal response pattern: a potential new
      signal-processing strategy.
AB  - The purpose of this paper is to introduce a new signal-processing strategy,
      spatiotemporal pattern correction (SPC), that is based on our knowledge of the
      level-dependent temporal response properties of auditory nerve fibers in normal
      and impaired ears. In normal-hearing listeners, tuning is sharp for low-level
      inputs and broadens as input level increases. When peripheral filters change
      their shape with input level, the phase properties of the filters and the latency
      of the filter's response also change. However, in listeners with hearing loss,
      tuning is broad for both low- and high-level inputs. Thus, there is little change
      in the phase properties of the filters for different input levels. The SPC
      strategy manipulates the temporal aspects of different frequency channels of
      sounds in an attempt to "correct" for this abnormal spatiotemporal response
      pattern of the impaired ear. Quality judgments and intelligibility measures of
      speech processed at various SPC strengths were obtained from a small group of
      normal-hearing listeners and listeners with hearing loss. In general, listeners
      with hearing loss preferred sentences with some degree of SPC processing, whereas
      normal-hearing listeners preferred unprocessed sentences. Benefit from SPC on the
      nonsense syllable test varied greatly across phonemes and listeners. A more
      comprehensive study of listeners with different degrees and configurations of
      hearing loss is needed to determine the amount of SPC benefit.

PMID- 16908881
TI  - Guidelines for statistical analysis of percentage of syllables stuttered data.
AB  - PURPOSE: The purpose of this study was to develop guidelines for the statistical
      analysis of percentage of syllables stuttered (%SS) data in stuttering research.
      METHOD: Data on %SS from various independent sources were used to develop a
      statistical model to describe this type of data. On the basis of this model, %SS
      data were simulated with varying means, standard deviations, and sample sizes.
      Four methods for analyzing %SS were compared. RESULTS: Results suggested that %SS
      data can be adequately modeled with a gamma distribution. Simulations based on a
      gamma distribution showed that all 4 analysis techniques performed favorably with
      respect to Type I error except for F. E. Satterthwaite's (1946) t test, which had
      increased Type I error on two occasions. Power was generally lower for the
      Wilcoxon-Mann-Whitney test compared with the other methods. Analysis of variance
      (ANOVA) performed on square-root-transformed data performed adequately under all
      scenarios, but ANOVA performed on nontransformed data and Satterthwaite's t test
      performed poorly when sample sizes were small or when sample sizes and variances
      of the groups were markedly different. CONCLUSIONS: Standard techniques such as t
      test and ANOVA are appropriate for most analysis scenarios with %SS data. Two
      occasions when this is not the case are when sample size is small, with fewer
      than 20 in each group, or when sample sizes and variances of the groups are
      markedly different. Under these circumstances, analyses should be based on
      standard methods, with a suitable transformation performed prior to analysis.

PMID- 16908880
TI  - Maturation of speech and language functional neuroanatomy in pediatric normal
      controls.
AB  - PURPOSE: This study explores the relationship between age and resting-state
      regional cerebral blood flow (rCBF) in regions associated with higher order
      language skills using a population of normal children, adolescents, and young
      adults. METHOD: rCBF was measured in 33 normal participants between the ages of 7
      and 19 years using single photon emission computed tomography. Participants' ages
      were regressed on rCBF values (normalized to whole-brain CBF) in 2 ways: (a)
      within anatomically defined, language-related regions of interest (ROIs)
      including Wernicke's area, Broca's area, angular gyrus, planum temporale, and
      Heschl's gyrus and (b) within clusters of voxels found to be significantly
      related to age in voxel-wise analyses. RESULTS: rCBF in all anatomically defined
      ROIs except Heschl's gyrus declined as a function of age. Additionally, voxel
      wise analyses revealed clusters where rCBF declined with age in left inferior
      parietal, left superior temporal, and right middle temporal regions-areas often
      implicated in higher order language functions. CONCLUSIONS: These data suggest
      that ongoing maturation (e.g., dendritic pruning) in higher order cognitive areas
      (e.g., angular gyrus) continues into adolescence, as reflected by declining rCBF,
      while the primary auditory area (Heschl's gyrus) has become a stable neuronal
      population by age 7 years.

PMID- 16908882
TI  - Perception of individuals with voice disorders by monolingual English, bilingual
      Cantonese-English, and bilingual Russian-English women.
AB  - PURPOSE: The purpose of this study was to examine the attitudes of monolingual
      English, bilingual Cantonese-English, and bilingual Russian-English speakers
      toward individuals with voice disorders. METHOD: In a mixed experimental design,
      a total of 30 older and 29 younger female listeners from the 3 language groups
      rated the voices of 10 females, each with a mild, moderate, or severe voice
      disorder or with no voice disorder. A semantic differential scale was used to
      rate the speakers on 21 attributes. RESULTS: Results indicate that the perception
      of individuals became increasingly negative as the severity of the disorder
      increased. Results also indicate that Cantonese-English bilinguals rated the
      individuals with severe voice disorders more negatively than did English
      monolinguals and that the language groups differed in their ratings for the
      attributes of beautiful, lovable, clean, and young. There was no overall effect
      of age of listener. CONCLUSION: The study demonstrates that although the language
      groups were uniform in ascribing more negative attributes to individuals as
      severity of the disorder increased, there were also significant differences
      between the groups. Exploration of these issues provides information useful to
      clinicians in setting priorities for intervention that take into account
      individuals' backgrounds as well as clinical factors.

PMID- 16908883
TI  - Perception of coarticulatory information in normal speech and dysarthria.
AB  - PURPOSE: This study addressed three research questions: (a) Can listeners use
      anticipatory vowel information in prevocalic consonants produced by talkers with
      dysarthria to identify the upcoming vowel? (b) Are listeners sensitive to
      interspeaker variation in anticipatory coarticulation during prevocalic
      consonants produced by healthy talkers and/or talkers with dysarthria, as
      measured by vowel identification accuracy? (c) Is interspeaker variation in
      anticipatory coarticulation reflected in measures of intelligibility? METHOD:
      Stimuli included 106 CVC words produced by 20 speakers with either Parkinson's
      disease or multiple sclerosis or by 16 healthy controls characterized by an
      operationally defined normal, under, or over level of anticipatory vowel
      coarticulation. Ten listeners were presented with prevocalic consonants for
      identification of the vowel. Ten additional listeners judged single-word
      intelligibility. An analysis of variance was used to determine differences in
      vowel identification accuracy and intelligibility as a function of speaker group,
      coarticulation level, and vowel type. RESULTS: Listeners accurately identified
      vowels produced by all speaker groups from the aperiodic portion of prevocalic
      consonants, but interspeaker variations in strength of coarticulation did not
      strongly affect vowel identification accuracy or intelligibility. CONCLUSIONS:
      Listeners appear to be tuned to similar types of information in the acoustic
      speech stream irrespective of the source or speaker, and any perceptual effects
      of interspeaker variation in coarticulation are subtle.

PMID- 16908884
TI  - A comparison of oral structure and oral-motor function in young males with
      fragile X syndrome and Down syndrome.
AB  - This study compared the oral structure and oral-motor skills of 59 boys with
      fragile X syndrome (FXS), 34 boys with Down syndrome (DS), and 36 developmentally
      similar typically developing (TD) boys. An adaptation of the J. Robbins and T.
      Klee (1987) Oral Speech Motor Protocol was administered to participants and their
      scores on measures of oral structure and accuracy on speech motor and oral-motor
      tasks were analyzed. Boys with FXS scored lower than TD boys on oral structure,
      most oral function tasks, and all speech function tasks. Boys with DS scored
      lower than boys with FXS and TD boys on oral structure, and lower than TD boys on
      1 oral function task and all speech function tasks. Boys with FXS and TD boys
      scored higher on speech function than oral function tasks, while boys with DS
      scored higher on oral function than speech function tasks. Boys with FXS and boys
      with DS repeated single syllable words with greater accuracy than multiple
      syllable words, while the TD boys produced both types of words with equal
      accuracy. These results suggest that boys with FXS and boys with DS exhibit
      atypical oral structure and motor function, yet differ in specific oral-motor
      patterns.

PMID- 16908885
TI  - More than ramps: accessible health care for people with disabilities.

PMID- 16908886
TI  - CMAJ and editorial autonomy.

PMID- 16908887
TI  - Privatization key issue for new CMA president.

PMID- 16908888
TI  - Pandemic threat overblown by both experts and media.

PMID- 16908889
TI  - Pharmacies receiving massive rebates from generic drug-makers.

PMID- 16908890
TI  - Systemic changes needed to resolve queues.

PMID- 16908891
TI  - Brand-name drug companies fail to meet R&D commitments.

PMID- 16908892
TI  - Is there another way to take account of noncompliance in randomized controlled
      trials?

PMID- 16908893
TI  - Inappropriate secretion of thyroid-stimulating hormone.

PMID- 16908894
TI  - A teenager with fever, rash and arthritis.

PMID- 16908895
TI  - National and provincial retention of medical graduates of Memorial University of
      Newfoundland.
AB  - BACKGROUND: Memorial University of Newfoundland (MUN) established its medical
      school in 1967 to meet the growing demand for physicians and alleviate the
      reliance on other Canadian and international medical schools for physicians.
      However, it is unclear how many of the graduates remained to practise in Canada
      and in Newfoundland and Labrador (NL). We conducted this study to identify the
      characteristics and predictors of MUN medical graduates working in Canada and NL
      after residency training. METHODS: We linked data from class lists, and alumni
      and postgraduate databases with data from the Southam Medical Database to
      determine 2004 practice locations for MUN graduates from 1973 to 1998. Multiple
      logistic regression analysis was used to identify predictors for working in
      Canada and in NL. RESULTS: Of the 1322 MUN graduates in our study, 1147 (86.8%)
      were working in Canada and 406 (30.7%) in NL in 2004. Predictors of physicians
      working in Canada included female sex (odds ratio [OR] 1.44, 95% confidence
      interval [CI] 1.01-2.04), being from Canada (OR 3.71, 95% CI 1.15-2.21),
      graduating in the 1980s (OR 1.52, 95% CI 1.02-2.24) and 1990s (OR 2.01, 95% CI
      1.31-3.09) and having done some or all residency training at MUN (OR 1.59, 95% CI
      1.53-9.01). Predictors of physicians working in NL included having a rural
      background (OR 1.37, 95% CI 1.04-1.81), being from NL (OR 9.23, 95% CI 5.52
      15.44) and having done some or all residency training at MUN (OR 5.28, 95% CI
      3.80-7.34). INTERPRETATION: The MUN medical school has made a substantial
      contribution to the local physician supply, producing over half the physicians
      working in the province in 2004. Initiatives to increase national and provincial
      retention of medical graduates include attracting rural students to medical
      careers, increasing admission of local students and providing incentives for
      graduates to complete their residency training in the province.

PMID- 16908896
TI  - Revascularization in patients with heart failure.
AB  - BACKGROUND: Although practice guidelines recommend coronary revascularization for
      patients with heart failure, the evidence to support this recommendation is weak.
      The objective of our study was to determine the association of coronary
      revascularization with survival in patients who have had heart failure. METHODS:
      Data were obtained from the Alberta Provincial Project for Outcomes Assessment in
      Coronary Heart Disease (APPROACH), a clinical outcome-monitoring initiative that
      has captured data on all patients undergoing cardiac catheterization in the
      province of Alberta since 1995. Our study included data from patients with a
      history of heart failure and with documented coronary artery disease; patients
      with normal coronary arteries or prior coronary artery bypass grafting (CABG)
      were excluded. We constructed survival curves and adjusted them by the corrected
      group prognosis method (incorporating all clinical variables in APPROACH).
      Propensity scores were used to account for clinical characteristics that could
      influence the decision to revascularize. RESULTS: A total of 2538 patients (mean
      age 68 yr, standard deviation [SD] 11 yr, 31% female) underwent
      revascularization; 1690 patients (mean age 69 [SD 11] yr, 34% female) did not.
      Crude 1-year mortality was 11.8% among patients who underwent revascularization,
      compared with 21.6% among those who did not. Adjusted survival curves diverged
      early and continued up to 7 years of follow-up (hazard ratio 0.50, 95% confidence
      interval 0.44-0.57). Propensity scores showed improved survival with
      revascularization across all quintiles of likelihood of revascularization.
      INTERPRETATION: This new evidence lends support to practice guidelines, which
      recommend revascularization in patients with heart failure and coronary disease.

PMID- 16908897
TI  - Autoimmune pancreatitis associated with renal lesions mimicking metastatic
      tumours.
AB  - Autoimmune pancreatitis is a chronic inflammatory disorder that is often
      misdiagnosed as pancreatic cancer. Since autoimmune pancreatitis is benign and
      responds to steroid management, it is important to diagnose it to avoid
      unnecessary surgical intervention. We describe a novel case of IgG4-associated
      autoimmune pancreatitis presenting with tubulointerstitial nephritis as renal
      lesions mimicking metastatic tumours but with no change in renal function.

PMID- 16908898
TI  - What makes medical graduates practise close to home?

PMID- 16908899
TI  - To revascularize or not to revascularize: a dilemma in heart failure.

PMID- 16908900
TI  - Patent nonsense: evidence tells of an industry out of social control.

PMID- 16908902
TI  - ["Yes to editorial independence, "no" to political interference].

PMID- 16908901
TI  - Probiotics for pediatric antibiotic-associated diarrhea: a meta-analysis of
      randomized placebo-controlled trials.
AB  - BACKGROUND: Antibiotic treatment is known to disturb gastrointestinal microflora,
      which results in a range of clinical symptoms--most notably, diarrhea. This is
      especially important in children, for whom antibiotics are prescribed frequently.
      Although meta-analyses have been conducted to evaluate the ability of probiotics
      to prevent antibiotic-induced diarrhea in the general population, little is known
      about which probiotic strains and doses might be of most benefit to children. Our
      objective in this study was to assess the efficacy of probiotics (of any
      specified strain or dose) for the prevention of antibiotic-associated diarrhea in
      children and to assess adverse events associated with the use of probiotics when
      coadministered with antibiotics to children. METHODS: A comprehensive search was
      performed of the major electronic databases (e.g., CENTRAL, MEDLINE, EMBASE,
      CINAHL, AMED) from their inception to January 2005. We also contacted experts and
      searched registries and meeting abstracts for additional relevant articles.
      Randomized controlled trials that compared probiotic treatment with placebo or no
      treatment, involving pediatric subjects less than 19 years of age were included.
      Two reviewers independently applied eligibility criteria and assessed the studies
      for methodological quality. Data were independently extracted by 2 reviewers and
      analyzed via the standard Cochrane methodology. RESULTS: Six studies were
      included (total n = 707 patients). The combined results, analyzed with a per
      protocol method that reported on the incidence of diarrhea during antibiotic
      treatment, showed significant benefit for the use of probiotics over placebo
      (relative risk [RR] 0.43, 95% confidence interval [CI] 0.25-0.75, Iota2 = 70.1%).
      In contrast, results from intention-to-treat analysis were nonsignificant overall
      (RR 1.01, 95% CI 0.64-1.61). Subgroup analysis on 4 studies that provided at
      least 5 billion single-strain colony-forming units (CFUs) daily (range 5.5-40 x
      10(9) Lactobacillus GG, L. sporogens or Saccharomyces boulardii) showed strong
      evidence with narrow CIs for the preventative effects of probiotics for
      antibiotic-associated diarrhea (RR 0.36, 95% CI 0.25-0.53, Iota2 = 3.5%). No
      serious adverse events were reported. INTERPRETATION: The potential protective
      effects of probiotics to prevent antibiotic-associated diarrhea in children do
      not withstand intention-to-treat analysis. Before routine use is recommended,
      further studies (with limited losses of subjects to follow-up) are merited.
      Trials should involve those probiotic strains and doses with the most promising
      evidence (i.e., Lactobacillus GG, L. sporogens or S. boulardii at 5-40 x 10(9)
      CFUs daily).

PMID- 16908903
TI  - ADRs and smart health cards.

PMID- 16908904
TI  - Chronic fatigue.

PMID- 16908905
TI  - Chronic fatigue.

PMID- 16908906
TI  - Accountability in CMAJ.

PMID- 16908908
TI  - Chronic fatigue.

PMID- 16908909
TI  - Barriers to tobacco cessation.

PMID- 16908910
TI  - Lessons from Hurricane Rita: organizing to provide medical care during a natural
      disaster.

PMID- 16908911
TI  - Assessment of the Medicare quality improvement organization program.
AB  - BACKGROUND: Studies have shown improvement in quality of health care in the
      United States. However, the factors responsible for this improvement are largely
      unknown. OBJECTIVE: To evaluate the effect of the Medicare Quality Improvement
      Organization (QIO) Program in 4 clinical settings by using performance data for
      41 quality measures during the 7th Scope of Work. DESIGN: Observational study in
      which differences in quality measures were compared between baseline and
      remeasurement periods for providers that received different levels of QIO
      interventions. SETTING: Nursing homes, home health agencies, hospitals, and
      physician offices in the 50 U.S. states, the District of Columbia, and 2 U.S.
      territories. PARTICIPANTS: Providers receiving focused QIO assistance related to
      quality measures and providers receiving general informational assistance from
      QIOs. MEASUREMENTS: 5 nursing home quality measures, 11 home health measures, 21
      hospital measures, and 4 physician office measures. RESULTS: For nursing home,
      home health, and physician office measures, providers recruited specifically by
      QIOs for receipt of assistance showed greater improvement in performance on 18 of
      20 measures than did providers who were not recruited; similar improvement was
      seen on the other 2 measures. Nursing homes and home health agencies improved
      more in all measures on which they chose to work with the QIO than in other
      measures. Nineteen of 21 hospital measures showed improvement; in this setting,
      QIOs were contracted for improvement initiatives solely at the statewide level.
      Overall, improvement was seen in 34 of 41 measures from baseline to remeasurement
      in the 7th Scope of Work. LIMITATIONS: As in any observational study, selection
      bias, regression to the mean, and secular trends may have influenced the results.
      CONCLUSIONS: These findings are consistent with an impact of the QIO Program and
      QIO technical assistance on the observed improvement. Future evaluations of the
      QIO Program will attempt to better address the limitations of the design of this
      study.

PMID- 16908912
TI  - Summaries for patients. Preclinical kidney disease in elderly people.

PMID- 16908913
TI  - Summaries for patients. The effect of nurse managers on heart failure
      complications in a minority community.

PMID- 16908914
TI  - Cystatin C and prognosis for cardiovascular and kidney outcomes in elderly
      persons without chronic kidney disease.
AB  - BACKGROUND: Cystatin C is an alternative measure of kidney function that may have
      prognostic importance among elderly persons who do not meet standard criteria for
      chronic kidney disease (estimated glomerular filtration rate [GFR] > or =60
      mL/min per 1.73 m2). OBJECTIVE: To evaluate cystatin C as a prognostic biomarker
      for death, cardiovascular disease, and incident chronic kidney disease among
      elderly persons without chronic kidney disease. DESIGN: Cohort study. SETTING:
      The Cardiovascular Health Study, a population-based cohort recruited from 4
      communities in the United States. PARTICIPANTS: 4663 elderly persons.
      MEASUREMENTS: Measures of kidney function were creatinine-based estimated GFR by
      using the Modification of Diet in Renal Disease equation and cystatin C
      concentration. Outcomes were death, cardiovascular death, noncardiovascular
      death, heart failure, stroke, myocardial infarction, and incident chronic kidney
      disease during follow-up (median, 9.3 years). RESULTS: At baseline, 78% of
      participants did not have chronic kidney disease (estimated GFR > or =60 mL/min
      per 1.73 m2) and mean cystatin C concentration, creatinine concentration, and
      estimated GFR were 1.0 mg/L, 79.6 micromol/L (0.9 mg/dL), and 83 mL/min per 1.73
      m2, respectively. Cystatin C concentrations (per SD, 0.18 mg/L) had strong
      associations with death (hazard ratio, 1.33 [95% CI, 1.25 to 1.40]),
      cardiovascular death (hazard ratio, 1.42 [CI, 1.30 to 1.54]), noncardiovascular
      death (hazard ratio, 1.26 [CI, 1.17 to 1.36]), incident heart failure (hazard
      ratio, 1.28 [CI, 1.17 to 1.40]), stroke (hazard ratio, 1.22 [CI, 1.08 to 1.38]),
      and myocardial infarction (hazard ratio, 1.20 [CI, 1.06 to 1.36]) among these
      participants. Serum creatinine concentrations had much weaker associations with
      each outcome and only predicted cardiovascular death. Participants without
      chronic kidney disease who had elevated cystatin C concentrations (> or =1.0
      mg/L) had a 4-fold risk for progressing to chronic kidney disease after 4 years
      of follow-up compared with those with cystatin C concentrations less than 1.0
      mg/L. LIMITATIONS: Because this study did not directly measure GFR or
      albuminuria, the extent to which cystatin C may be influenced by nonrenal factors
      was not determined and participants with albuminuria might have been
      misclassified as having no kidney disease. CONCLUSIONS: Among elderly persons
      without chronic kidney disease, cystatin C is a prognostic biomarker of risk for
      death, cardiovascular disease, and chronic kidney disease. In this setting,
      cystatin C seems to identify a "preclinical" state of kidney dysfunction that is
      not detected with serum creatinine or estimated GFR.

PMID- 16908915
TI  - Using standardized serum creatinine values in the modification of diet in renal
      disease study equation for estimating glomerular filtration rate.
AB  - BACKGROUND: Glomerular filtration rate (GFR) estimates facilitate detection of
      chronic kidney disease but require calibration of the serum creatinine assay to
      the laboratory that developed the equation. The 4-variable equation from the
      Modification of Diet in Renal Disease (MDRD) Study has been reexpressed for use
      with a standardized assay. OBJECTIVE: To describe the performance of the revised
      4-variable MDRD Study equation and compare it with the performance of the 6
      variable MDRD Study and Cockcroft-Gault equations. DESIGN: Comparison of
      estimated and measured GFR. SETTING: 15 clinical centers participating in a
      randomized, controlled trial. PATIENTS: 1628 patients with chronic kidney disease
      participating in the MDRD Study. MEASUREMENTS: Serum creatinine levels were
      calibrated to an assay traceable to isotope-dilution mass spectrometry.
      Glomerular filtration rate was measured as urinary clearance of 125I-iothalamate.
      RESULTS: Mean measured GFR was 39.8 mL/min per 1.73 m2 (SD, 21.2). Accuracy and
      precision of the revised 4-variable equation were similar to those of the
      original 6-variable equation and better than in the Cockcroft-Gault equation,
      even when the latter was corrected for bias, with 90%, 91%, 60%, and 83% of
      estimates within 30% of measured GFR, respectively. Differences between measured
      and estimated GFR were greater for all equations when the estimated GFR was 60
      mL/min per 1.73 m2 or greater. LIMITATIONS: The MDRD Study included few patients
      with a GFR greater than 90 mL/min per 1.73 m2. Equations were not compared in a
      separate study sample. CONCLUSIONS: The 4-variable MDRD Study equation provides
      reasonably accurate GFR estimates in patients with chronic kidney disease and a
      measured GFR of less than 90 mL/min per 1.73 m2. By using the reexpressed MDRD
      Study equation with the standardized serum creatinine assay, clinical
      laboratories can report more accurate GFR estimates.

PMID- 16908916
TI  - The association between common vitamin D receptor gene variations and
      osteoporosis: a participant-level meta-analysis.
AB  - BACKGROUND: Polymorphisms of the vitamin D receptor (VDR) gene have been
      implicated in the genetic regulation of bone mineral density (BMD). However, the
      clinical impact of these variants remains unclear. OBJECTIVE: To evaluate the
      relation between VDR polymorphisms, BMD, and fractures. DESIGN: Prospective
      multicenter large-scale association study. SETTING: The Genetic Markers for
      Osteoporosis consortium, involving 9 European research teams. PARTICIPANTS:
      26,242 participants (18,405 women). MEASUREMENTS: Cdx2 promoter, FokI, BsmI,
      ApaI, and TaqI polymorphisms; BMD at the femoral neck and the lumbar spine by
      dual x-ray absorptiometry; and fractures. RESULTS: Comparisons of BMD at the
      lumbar spine and femoral neck showed nonsignificant differences less than 0.011
      g/cm2 for any genotype with or without adjustments. A total of 6067 participants
      reported a history of fracture, and 2088 had vertebral fractures. For all VDR
      alleles, odds ratios for fractures were very close to 1.00 (range, 0.98 to 1.02)
      and collectively the 95% CIs ranged from 0.94 (lowest) to 1.07 (highest). For
      vertebral fractures, we observed a 9% (95% CI, 0% to 18%; P = 0.039) risk
      reduction for the Cdx2 A-allele (13% risk reduction in a dominant model).
      LIMITATIONS: The authors analyzed only selected VDR polymorphisms. Heterogeneity
      was detected in some analyses and may reflect some differences in collection of
      fracture data across cohorts. Not all fractures were related to osteoporosis.
      CONCLUSIONS: The FokI, BsmI, ApaI, and TaqI VDR polymorphisms are not associated
      with BMD or with fractures, but the Cdx2 polymorphism may be associated with risk
      for vertebral fractures.

PMID- 16908917
TI  - Does pay-for-performance improve the quality of health care?
AB  - BACKGROUND: Most physicians and hospitals are paid the same regardless of the
      quality of the health care they provide. This produces no financial incentives
      and, in some cases, produces disincentives for quality. Increasing numbers of
      programs link payment to performance. PURPOSE: To systematically review studies
      assessing the effect of explicit financial incentives for improved performance on
      measures of health care quality. DATA SOURCES: PubMed search of English-language
      literature (1 January 1980 to 14 November 2005), and reference lists of retrieved
      articles. STUDY SELECTION: Empirical studies of the relationship between explicit
      financial incentives designed to improve health care quality and a quantitative
      measure of health care quality. DATA EXTRACTION: The authors categorized studies
      according to the level of the incentive (individual physician, provider group, or
      health care payment system) and the type of quality measure rewarded. DATA
      SYNTHESIS: Thirteen of 17 studies examined process-of-care quality measures, most
      of which were for preventive services. Five of the 6 studies of physician-level
      financial incentives and 7 of the 9 studies of provider group-level financial
      incentives found partial or positive effects on measures of quality. One of the 2
      studies of incentives at the payment-system level found a positive effect on
      access to care, and 1 showed evidence of a negative effect on access to care for
      the sickest patients. In all, 4 studies suggested unintended effects of
      incentives. The authors found no studies examining the optimal duration of
      financial incentives for quality or the persistence of their effects after
      termination. Only 1 study addressed cost-effectiveness. LIMITATIONS: Few
      empirical studies of explicit financial incentives for quality were available for
      review. CONCLUSIONS: Ongoing monitoring of incentive programs is critical to
      determine the effectiveness of financial incentives and their possible unintended
      effects on quality of care. Further research is needed to guide implementation of
      financial incentives and to assess their cost-effectiveness.

PMID- 16908918
TI  - Effects of nurse management on the quality of heart failure care in minority
      communities: a randomized trial.
AB  - BACKGROUND: Despite therapies proven effective for heart failure with systolic
      dysfunction, the condition continues to cause substantial hospitalization,
      disability, and death, especially among African- American and other nonwhite
      populations. OBJECTIVE: To compare the effects of a nurse-led intervention
      focused on specific management problems versus usual care among ethnically
      diverse patients with systolic dysfunction in ambulatory care practices. DESIGN:
      Randomized effectiveness trial conducted from September 2000 to September 2002.
      SETTING: The 4 hospitals in Harlem, New York. PATIENTS: 406 adults (45.8% were
      non-Hispanic black adults, 32.5% were Hispanic adults, 46.3% were women, and
      36.7% were > or =65 years of age) who met eligibility criteria: systolic
      dysfunction, English- or Spanish-language speakers, community-dwelling patients,
      and ambulatory care practice patients. INTERVENTION: During a 12-month
      intervention, bilingual nurses counseled patients on diet, medication adherence,
      and self-management of symptoms through an initial visit and regularly scheduled
      follow-up telephone calls and facilitated evidence-based changes to medications
      in discussions with patients' clinicians. MEASUREMENTS: Hospitalizations (in 406
      of 406 patients during follow-up) and self-reported functioning (in 286 of 406
      patients during follow-up) at 12 months. RESULTS: At 12 months, nurse management
      patients had had fewer hospitalizations (143 hospitalizations vs. 180
      hospitalizations; adjusted difference, -0.13 hospitalization/person-year [95% CI,
      -0.25 to -0.001 hospitalization/person-year]) than usual care patients. They also
      had better functioning: The Short Form-12 physical component score was 39.9
      versus 36.3, respectively (difference, 3.6 [CI, 1.2 to 6.1]), and the Minnesota
      Living with Heart Failure Questionnaire score was 38.6 versus 47.3, respectively
      (difference, -8.8 [CI, -15.3 to -2.2]). Through 12 months, 22 deaths occurred in
      each group and percentages of patients who were hospitalized at least once were
      similar in each group (30.5% of nurse management patients vs. 36.5% of control
      patients; adjusted difference, -7.1 percentage points [CI, -16.9 to 2.6
      percentage points]). LIMITATIONS: Three nurses at 4 hospitals delivered
      interventions in this modest-sized trial, and 75% of the participants were from 1
      site. It is not clear which aspects of the complex intervention accounted for the
      results. CONCLUSIONS: Nurse management can improve functioning and modestly lower
      hospitalizations in ethnically diverse ambulatory care patients who have heart
      failure with systolic dysfunction. Sustaining improved functioning may require
      continuing nurse contact.

PMID- 16908919
TI  - Narrative review: the promotion of gabapentin: an analysis of internal industry
      documents.
AB  - BACKGROUND: Internal documents from the pharmaceutical industry provide a unique
      window for understanding the structure and methods of pharmaceutical promotion.
      Such documents have become available through litigation concerning the promotion
      of gabapentin (Neurontin, Pfizer, Inc., New York, New York) for off-label uses.
      PURPOSE: To describe how gabapentin was promoted, focusing on the use of medical
      education, research, and publication. DATA SOURCES: Court documents available to
      the public from United States ex. rel David Franklin vs. Pfizer, Inc., and Parke
      Davis, Division of Warner-Lambert Company, mostly from 1994-1998. DATA
      EXTRACTION: All documents were reviewed by 1 author, with selected review by
      coauthors. Marketing strategies and tactics were identified by using an iterative
      process of review, discussion, and re-review of selected documents. DATA
      SYNTHESIS: The promotion of gabapentin was a comprehensive and multifaceted
      process. Advisory boards, consultants meetings, and accredited continuing medical
      education events organized by third-party vendors were used to deliver
      promotional messages. These tactics were augmented by the recruitment of local
      champions and engagement of thought leaders, who could be used to communicate
      favorable messages about gabapentin to their physician colleagues. Research and
      scholarship were also used for marketing by encouraging "key customers" to
      participate in research, using a large study to advance promotional themes and
      build market share, paying medical communication companies to develop and publish
      articles about gabapentin for the medical literature, and planning to suppress
      unfavorable study results. LIMITATIONS: Most available documents were submitted
      by the plaintiff and may not represent a complete picture of marketing practices.
      CONCLUSION: Activities traditionally considered independent of promotional
      intent, including continuing medical education and research, were extensively
      used to promote gabapentin. New strategies are needed to ensure a clear
      separation between scientific and commercial activity.

PMID- 16908920
TI  - Update in gastroenterology and hepatology.

PMID- 16908921
TI  - Decreased kidney function in the elderly: clinical and preclinical, neither
      benign.

PMID- 16908922
TI  - Making sense of puzzling genetic association studies: a team approach.

PMID- 16908923
TI  - Safeguarding patient welfare: who's in charge?

PMID- 16908924
TI  - The "practice" of medicine.

PMID- 16908925
TI  - Lipohypertrophy in acromegaly induced by the new growth hormone receptor
      antagonist pegvisomant.

PMID- 16908927
TI  - Pulmonary embolism in patients with unexplained exacerbations of chronic
      obstructive pulmonary disease.

PMID- 16908928
TI  - Health Insurance Portability and Accountability Act Privacy rule causes ongoing
      concerns among clinicians and researchers.

PMID- 16908929
TI  - Which breast cancer patients should really worry about radiation-induced heart
      disease--and how much?

PMID- 16908930
TI  - Heart of darkness: the downside of trastuzumab.

PMID- 16908931
TI  - Somatic activation of KIT in distinct subtypes of melanoma.
AB  - PURPOSE: Melanomas on mucosal membranes, acral skin (soles, palms, and nail bed),
      and skin with chronic sun-induced damage have infrequent mutations in BRAF and
      NRAS, genes within the mitogen-activated protein (MAP) kinase pathway commonly
      mutated in melanomas on intermittently sun-exposed skin. This raises the question
      of whether other aberrations are occurring in the MAP kinase cascade in the
      melanoma types with infrequent mutations of BRAF and NRAS. PATIENTS AND METHODS:
      We analyzed array comparative genomic hybridization data from 102 primary
      melanomas (38 from mucosa, 28 from acral skin, and 18 from skin with and 18 from
      skin without chronic sun-induced damage) for DNA copy number aberrations specific
      to melanoma subtypes where mutations in BRAF and NRAS are infrequent. A narrow
      amplification on 4q12 was found, and candidate genes within it were analyzed.
      RESULTS: Oncogenic mutations in KIT were found in three of seven tumors with
      amplifications. Examination of all 102 primary melanomas found mutations and/or
      copy number increases of KIT in 39% of mucosal, 36% of acral, and 28% of
      melanomas on chronically sun-damaged skin, but not in any (0%) melanomas on skin
      without chronic sun damage. Seventy-nine percent of tumors with mutations and 53%
      of tumors with multiple copies of KIT demonstrated increased KIT protein levels.
      CONCLUSION: KIT is an important oncogene in melanoma. Because the majority of the
      KIT mutations we found in melanoma also occur in imatinib-responsive cancers of
      other types, imatinib may offer an immediate therapeutic benefit for a
      significant proportion of the global melanoma burden.

PMID- 16908932
TI  - T-cell immunity to the folate receptor alpha is prevalent in women with breast or
      ovarian cancer.
AB  - PURPOSE: Studies have demonstrated that the generation of immunity to tumor
      antigens is associated with improved prognosis for many cancers. A candidate
      antigen is the folate receptor alpha (FRalpha), which is overexpressed in breast
      and ovarian cancers. Our goal in this study was to attain a better understanding
      of the extent of endogenous FRalpha immunity. METHODS: Using a CD4+ T cell
      epitope prediction algorithm, we predicted promiscuous epitopes of FRalpha, and
      tested for immunity in 30 breast (n = 17) or ovarian (n = 13) cancer patients and
      18 healthy donors using enzyme-linked immunospot analysis. RESULTS: Fourteen
      peptides were predicted, seven each from the carboxy- and amino-terminus halves
      of the protein. More than 70% of patients demonstrated immunity to at least one
      FRalpha peptide. Patients responded to an average of 3 +/- 0.5 peptides, whereas
      healthy donors responded to 1 +/- 0.4 peptides (P = .004). Five peptides were
      recognized by more than 25% of patients. Responses to three peptides were higher
      (P < .05) in patients than in healthy donors, suggesting augmented immunity.
      Compared with healthy individuals, patients developed higher immunity to the
      amino-terminus half of the receptor (P = .03). There was no difference between
      each group in the responses to nonspecific (P = .2) and viral stimuli (P = .5).
      Lastly, patients demonstrated elevated levels of FRalpha antibodies consistent
      with a coordinated immune response. CONCLUSION: These findings demonstrate that
      the FRalpha is a target of the immune system in breast and ovarian cancer
      patients. Understanding which antigens are targeted by the immune system may be
      important for prognosis or immune-based therapies.

PMID- 16908933
TI  - Late cardiac mortality and morbidity in early-stage breast cancer patients after
      breast-conservation treatment.
AB  - PURPOSE: Several studies have reported increased cardiac mortality related to the
      use of left-sided breast or chest-wall irradiation. This study was undertaken as
      a comprehensive examination of the long-term cardiac mortality and morbidity
      after breast irradiation using contemporary irradiation techniques. METHODS: The
      medical records of 961 consecutive patients presenting between 1977 and 1994 with
      stage I or II breast cancer treated with breast conservation treatment were
      reviewed. Data was recorded on baseline pretreatment patient, tumor and treatment
      characteristics and on subsequent cancer or cardiac related events. The median
      follow-up time was 12 years. RESULTS: There was no difference in overall
      mortality from any cardiac cause (P = .25). Death from any cardiac cause occurred
      in 2% of right-sided patients and 3.5% of left-sided patients. However, in the
      second decade after treatment, there was a higher rate of cardiac deaths in left
      sided patients, with a cumulative risk of 6.4% (95% CI, 3.5% to 11.5%) for left
      sided compared with 3.6% (95% CI, 1.8% to 7.2%) for right-sided patients at 20
      years. There were statistically higher rates of chest pain, coronary artery
      disease, and myocardial infarction diagnosed in left-sided patients (all P < or =
      .002). The presence of hypertension was associated with a higher risk of coronary
      artery disease in left-sided patients. CONCLUSION: Irradiation to the left breast
      is not associated with a higher risk of cardiac death up to 20 years after
      treatment, but is associated with an increased rate of diagnoses of coronary
      artery disease and myocardial infarction compared with right breast treatment.

PMID- 16908934
TI  - Long-term cardiac tolerability of trastuzumab in metastatic breast cancer: the
      M.D. Anderson Cancer Center experience.
AB  - PURPOSE: To evaluate the cardiac safety of long-term trastuzumab therapy in
      patients with human epidermal growth receptor 2 (HER2) -overexpressing metastatic
      breast cancer (MBC) treated at The University of Texas M.D. Anderson Cancer
      Center (Houston, TX). PATIENTS AND METHODS: Among 218 MBC patients treated with
      trastuzumab-based therapy for at least 1 year, 173 patients were assessable for
      cardiac toxicity. Cardiac events (CEs) were defined as follows: asymptomatic
      decrease of left ventricular ejection fraction (LVEF) below 50%; decrease of 20
      percentage points in LVEF compared with the baseline; or signs or symptoms of
      congestive heart failure (CHF). RESULTS: The median cumulative time for
      trastuzumab administration was 21.3 months. The median follow-up was 32.6 months
      (range, 11.8 to 79.0 months). Forty-nine patients (28%) experienced a CE: three
      patients (1.7%) had an asymptomatic decrease in the LVEF of 20 percentage points,
      27 patients (15.6%) experienced grade 2 cardiac toxicity, and 19 patients (10.9%)
      experienced grade 3 cardiac toxicity. All but three patients had improved LVEF or
      symptoms of CHF with trastuzumab discontinuation and appropriate therapy. There
      was one cardiac-related death (0.5%). Baseline LVEF was significantly associated
      with CE (hazard ratio, 0.94; P = .001). The hazard of a CE among patients taking
      concomitant taxanes was higher early in the follow-up period but declined during
      the course of follow-up. CONCLUSION: The risk of cardiac toxicity of long-term
      trastuzumab-based therapy is acceptable in this population, and this toxicity is
      reversible in the majority of the patients. In patients who have experienced a
      CE, additional treatment with trastuzumab can be considered after recovery of
      cardiac function.

PMID- 16908935
TI  - Genotype-phenotype comparison of German MLH1 and MSH2 mutation carriers
      clinically affected with Lynch syndrome: a report by the German HNPCC Consortium.
AB  - PURPOSE: Lynch syndrome is linked to germline mutations in mismatch repair genes.
      We analyzed the genotype-phenotype correlations in the largest cohort so far
      reported. PATIENTS AND METHODS: Following standard algorithms, we identified 281
      of 574 unrelated families with deleterious germline mutations in MLH1 (n = 124)
      or MSH2 (n = 157). A total of 988 patients with 1,381 cancers were included in
      this analysis. RESULTS: We identified 181 and 259 individuals with proven or
      obligatory and 254 and 294 with assumed MLH1 and MSH2 mutations, respectively.
      Age at diagnosis was younger both in regard to first cancer (40 v 43 years; P <
      .009) and to first colorectal cancer (CRC; 41 v 44 years; P = .004) in MLH1 (n =
      435) versus MSH2 (n = 553) mutation carriers. In both groups, rectal cancers were
      remarkably frequent, and the time span between first and second CRC was smaller
      if the first primary occurred left sided. Gastric cancer was the third most
      frequent malignancy occurring without a similarly affected relative in most
      cases. All prostate cancers occurred in MSH2 mutation carriers. CONCLUSION: The
      proportion of rectal cancers and shorter time span to metachronous cancers
      indicates the need for a defined treatment strategy for primary rectal cancers in
      hereditary nonpolyposis colorectal cancer patients. Male MLH1 mutation carriers
      require earlier colonoscopy beginning at age 20 years. We propose regular gastric
      surveillance starting at age 35 years, regardless of the familial occurrence of
      this cancer. The association of prostate cancer with MSH2 mutations should be
      taken into consideration both for clinical and genetic counseling practice.

PMID- 16908936
TI  - Detection of aberrant methylation of four genes in plasma DNA for the detection
      of breast cancer.
AB  - PURPOSE: Novel approaches to breast cancer screening are necessary, especially in
      the developing world where mammography is not feasible. In this study, we
      explored the hypothesis that blood-based biomarkers have potential for biomarkers
      for breast cancer. PATIENTS AND METHODS: We first determined the frequency of
      aberrant methylation of four candidate genes (APC, GSTP1, Rassf1A, and RARbeta2)
      in primary breast cancer tissues from West African women with predominantly
      advanced cancers. We used a high-throughput DNA methylation assay (quantitative
      methylation-specific polymerase chain reaction) to examine plasma from 93 women
      with breast cancer and 76 controls for the presence of four methylated genes.
      Samples were randomly divided evenly into training and validation data sets.
      Cutoff values for gene positivity of the plasma-based assay and the gene panel
      were determined by receiver operating characteristic curves in the training data
      set and subsequently evaluated as a screening tool in the validation data set.
      RESULTS: Methylation of at least one gene resulted in a sensitivity of 62% and a
      specificity of 87%. Moreover, the assay successfully detected 33% (eight of 24)
      of early-stage tumors. CONCLUSION: These data suggest that epigenetic markers in
      plasma may be of interest for detection of breast cancer. Identification of
      additional breast cancer specific methylated genes with higher prevalence in
      early stage cancers would improve this approach.

PMID- 16908937
TI  - Phase II study of sorafenib in patients with advanced hepatocellular carcinoma.
AB  - PURPOSE: This phase II study of sorafenib, an oral multikinase inhibitor that
      targets Raf kinase and receptor tyrosine kinases, assessed efficacy, toxicity,
      pharmacokinetics, and biomarkers in advanced hepatocellular carcinoma (HCC)
      patients. METHODS: Patients with inoperable HCC, no prior systemic treatment, and
      Child-Pugh (CP) A or B, received continuous, oral sorafenib 400 mg bid in 4-week
      cycles. Tumor response was assessed every two cycles using modified WHO criteria.
      Sorafenib pharmacokinetics were measured in plasma samples. Biomarker analysis
      included phosphorylated extracellular signal regulated kinase (pERK) in
      pretreatment biopsies (immunohistochemistry) and blood-cell RNA expression
      patterns in selected patients. RESULTS: Of 137 patients treated (male, 71%;
      median age, 69 years), 72% had CP A, and 28% had CP B. On the basis of
      independent assessment, three (2.2%) patients achieved a partial response, eight
      (5.8%) had a minor response, and 46 (33.6%) had stable disease for at least 16
      weeks. Investigator-assessed median time to progression (TTP) was 4.2 months, and
      median overall survival was 9.2 months. Grade 3/4 drug-related toxicities
      included fatigue (9.5%), diarrhea (8.0%), and hand-foot skin reaction (5.1%).
      There were no significant pharmacokinetic differences between CP A and B
      patients. Pretreatment tumor pERK levels correlated with TTP. A panel of 18
      expressed genes was identified that distinguished "nonprogressors" from
      "progressors" with an estimated 100% accuracy. CONCLUSION: Although single-agent
      sorafenib has modest efficacy in HCC, the manageable toxicity and mechanisms of
      action support a role for combination regimens with other anticancer agents.

PMID- 16908939
TI  - Measles encephalitis: direct viral invasion or autoimmune-mediated inflammation?

PMID- 16908938
TI  - Vogt-Koyanagi-Harada disease and polymorphonuclear leuokocyts pleocytosis in
      cerebrospinal fluid.

PMID- 16908940
TI  - Characteristics of asthma resistant to moderate dose inhaled corticosteroid
      treatment on bronchial hyperresponsiveness.
AB  - OBJECT: This study was performed to determine the clinical characteristics of
      asthmatics with bronchial hyperresponsiveness (BHR) that could not be normalized
      by 6 months of treatment with a moderate dose of an inhaled corticosteroid (ICS).
      METHODS: Thirty-four symptomatic patients with mild to moderate asthma, who had
      never received any ICS, were treated with 200 mug of inhaled fluticasone
      propionate twice a day for 6 months. Spirometry, BHR to methacholine, exhaled
      nitric oxide (NO) and eosinophils in induced sputum were examined before and 2
      and 6 months after beginning treatment. RESULTS: FEV1 was increased and bronchial
      responsiveness, exhaled NO and sputum eosinophilia were significantly decreased 2
      and 6 months after starting ICS treatment. Bronchial responsiveness was further
      decreased at 6 months together with a further increase in FEV1. In 13 patients,
      BHR was not normalized despite the 6 months of treatment. This group showed a
      higher prevalence of males, those with a smoking history and airflow limitation,
      a higher eosinophil count in the sputum following 6 months of treatment and a
      longer history of asthma. Multiple, stepwise, linear regression analysis showed
      that sputum eosinophilia and lower FEV1/FVC following 6 months of treatment and a
      longer history of asthma were significant independent determinants for BHR after
      6 months of ICS treatment. CONCLUSIONS: These findings suggest that the
      resistance to a moderate dose of ICS for BHR in asthmatics may be significantly
      associated with remained airflow limitation, eosinophilic airway inflammation
      resistive to moderate dose of ICS, and delayed introduction of ICS therapy.

PMID- 16908941
TI  - Abducens nerve palsy and postganglionic Horner syndrome with or without severe
      headache.
AB  - OBJECTIVE: To report the clinical features of 9 patients with both abducens nerve
      palsy and postganglionic Horner syndrome. PATIENTS AND METHODS: Nine patients
      with this symptom combination were examined by our Neuro-ophthalmology Clinic in
      Nihon University Itabashi Hospital between 1978 and 2004. Patient ages ranged
      from 28 to 63 years (average 47.2+/-8.7 years). Six patients were males and 3
      were females. Primary diseases, accompanying symptoms and prognoses were
      surveyed. RESULTS: In primary diseases, neoplasm in the cavernous sinus was
      observed in 2 patients, sphenoidal sinus cyst in 2, intra-cavernous carotid
      aneurysm in 2, epipharynx carcinoma in 1, chordoma in the base of the skull in 1,
      and meningioma in the middle cranial fossa in 1. Five patients with extra
      cavernous sinus lesions; sphenoidal sinus cyst, epipharynx carcinoma, chordoma
      and meningioma, complained of severe headache. However, in patients without
      severe headache, intra-cavernous sinus lesions such as carotid aneurysm and
      metastatic carcinoma were detected. After therapy, abducens nerve palsy improved
      in 5 patients, however, Horner syndrome persisted in all patients. CONCLUSION: We
      emphasize that this symptom combination is an important sign of lesions in the
      posterior portion of the cavernous sinus or in its vicinity. Moreover, the
      presence or absence of severe headache depends on whether the lesion is in the
      intra-cavernous or extra-cavernous sinus.

PMID- 16908942
TI  - Simple method of detecting sarcoptes scabiei var hominis mites among bedridden
      elderly patients suffering from severe scabies infestation using an adhesive
      tape.
AB  - OBJECT: Scabies infestation is very common among bedridden elderly patients. The
      standard method of diagnosis for scabies by scraping the skin requires some
      skill. Therefore, dermatologists employ this method. However, dermatologists are
      usually not present in most long-term nursing units. Thus, we tried to catch
      mites using a strong transparent adhesive tape commercially available for packing
      use as an alternative method for the diagnosis of severe scabies infestation.
      METHODS: After firmly applying the adhesive side of the tape onto an appropriate
      skin lesion of patients, the tape was pulled off and transferred directly onto a
      slide for microscopy, affixing the adhered separated part of the corneal skin.
      PATIENTS: When a massive outbreak of scabies infestation occurred in May 2004 at
      the nursing unit of K hospital with thirty-one bedridden elderly patients, we
      tried to detect scabies mite using an adhesive tape. RESULTS: We could detect
      mites from six patients using this tape method. The diagnosis was confirmed by
      the standard scraping method. By the tape method we could observe some mites
      moving around and also could see a striated structure with dark red or weak red
      color or gray color granule-like constitution on the body of some mites. We found
      mites only on the skin of the fingers and toes where the skin of a patient is
      thin. Recently, massive scabies infestation in elderly long-term residents has
      been reported elsewhere. This tape method is simple and useful for diagnosis of
      severe scabies infestation in long-term nursing units.

PMID- 16908943
TI  - Late-onset life threatening hemorrhage of omeprazole-resistant duodenal ulcer
      managed by interventional radiology: report of a case.
AB  - A 67-year-old diabetic man was emergently hospitalized in our department because
      of a huge duodenal ulcer without visible vessels. Despite of intravenous
      administration of 40 mg omeprazole and fasting with intravenous nutritional
      support, endoscopically unmanageable massive bleeding occurred on the 8th
      hospital day. Emergent angiography showed extravasation of contrast media from a
      duodenal branch of the proper hepatic artery, and superselective arterial
      embolization was successfully achieved. The patient recovered from the
      hemorrhagic shock and underwent subsequent successful surgery. Analysis of
      CYP2C19 enzyme genotype indicated the patient was a homozygous extensive
      metabolizer, considered a poor responder for omeprazole treatment.

PMID- 16908944
TI  - Successful coil embolization with assistance of coronary stenting in an adult
      patient with a huge coronary arterial-right atrial fistula.
AB  - A 55 year-old man with huge coronary artery fistula to the right atrium is
      presented. The Qp/Qs ratio was 1.6. We failed to place simultaneously three
      interlocking detachable coils for closing the fistula, because the coils were
      washed out into the right atrium. We deployed the coronary stent at the distal
      portion of the coronary artery. This procedure enabled us to anchor 7
      electrically or interlocking detachable coils and to interrupt the shunt flow. A
      Doppler flow wire was useful to reveal instantaneously the extent of flow
      reduction even when contrast angiography was not performed in each procedure.

PMID- 16908945
TI  - Chronic inflammatory demyelinating polyneuropathy associated with idiopathic
      hemochromatosis.
AB  - We describe a 50-year-old woman who developed chronic inflammatory demyelinating
      polyneuropathy (CIDP) one year after onset of hemochromatosis. Electrodiagnostic
      studies showed evidence of multifocal demyelination. Marked
      hypergammaglobulinemia with positive anti-nuclear and anti-DNA antibodies was
      found. Corticosteroid treatment resulted in a significant lessening of
      neurological symptoms. This is the first case of CIDP with hemochromatosis. The
      association may be coincidental, but the altered immune system by hemochromatosis
      was possibly related to the development of CIDP in this patient.

PMID- 16908946
TI  - Subacute combined degeneration of the spinal cord concomitant with gastric
      cancer.
AB  - We report a rare case of subacute combined degeneration of the spinal cord
      concomitant with gastric cancer. A 67-year-old man was admitted because of
      posterior column symptoms, pyramidal tract sign and peripheral neuropathy with
      severe hyperchromic anemia. He was treated with mecobalamin 1 mg IM, after which
      his anemia and neurological signs recovered. He was diagnosed as having subacute
      combined degeneration with pernicious anemia. Subsequent stomach biopsy revealed
      gastric cancer, and the patient underwent gastrectomy. It is a well known
      association that chronic atrophic gastritis is associated with gastric cancer or
      subacute combined degeneration. Our findings suggest that in this case subacute
      combined degeneration and gastric cancer are independent of each other; rather,
      both resulted from chronic atrophic gastritis.

PMID- 16908947
TI  - Psoriasis improved by intravenous immunoglobulin therapy.

PMID- 16908948
TI  - The analysis and diagnosis of unstable behavior of the blood vessel wall with an
      aneurysm based on noise science.
AB  - Previously, one of the authors developed a noninvasive measurement method of
      acceleration and deceleration during the expansion process of the blood vessel
      wall under pulsatile pressure flow by measuring the strain rate of the blood
      vessel wall using a supersonic Doppler effect sensor aided by computer analysis
      (DPC method). In this paper, on the basis of the analysis of chaos theory, that
      is, the complexity of science, the unstable behavior of the blood vessel wall
      with an aneurysm was investigated by identifying the characteristic DPC wave
      forms induced by the onset and progression of aneurysm. These results showed that
      unstable dynamic behavior of the blood vessel wall occurs due to the progression
      of the aneurysm. Furthermore, using the theoretical analysis of chaos, this
      unstable behavior of the blood vessel wall was quantified and the fundamental
      principle of a noninvasive diagnostic method of the progressive degree of
      aneurysm was proposed.

PMID- 16908949
TI  - Impact of C-reactive protein on the likelihood of carotid atherosclerosis in
      Japanese adults.
AB  - OBJECTIVE: Several cohort studies have shown a link between serum C-reactive
      protein (CRP) and subsequent cardiovascular disease; however, the role of CRP as
      an independent risk factor remains controversial. We therefore investigated the
      association between CRP and sclerotic lesions of common carotid atherosclerosis.
      PATIENTS AND METHODS: We evaluated sclerotic lesions of common carotid arterial
      intima-media thickness (IMT) by ultrasonography in 139 men aged 67 +/- 15 years
      and 201 women aged 75 +/- 10 years. To investigate the relation between CRP and
      various confounding factors, subjects were divided into four groups based on the
      quartile of CPR. RESULTS: Carotid IMT values were significantly higher in groups
      with higher CRP (p = 0.022). To identify the possible CRP level and risk factor
      interactions for IMT, multiple regression analysis for IMT was performed based on
      risk factors in subjects with a specific CRP level. It was shown that age,
      smoking status, systolic blood pressure (SBP) and LDL cholesterol were
      significantly associated with IMT in subjects in the lower CRP groups (CRP-1
      approximately CRP-3), and age, SBP and presence of diabetes mellitus in the
      highest CRP group (CRP-4). To further investigate whether the interaction between
      CRP and conventional risk factors could influence IMT, a general linear model
      demonstrated that interaction between CRP and the presence of diabetes mellitus
      (F = 4.754 p = 0.030) was significantly associated with IMT, in addition to sex,
      age, SBP, antihypertensive drug use, LDL cholesterol and HDL cholesterol.
      CONCLUSIONS: This finding indicates that the association between CRP and IMT
      significantly differed between subjects with and without diabetes mellitus.

PMID- 16908950
TI  - Trichostatin A, an inhibitor of histone deacetylase, inhibits smooth muscle cell
      proliferation via induction of p21(WAF1).
AB  - The proliferation of vascular smooth muscle cells (VSMCs) can contribute to a
      variety of pathological states, including atherosclerosis and post-angioplasty
      restenosis. The p21(WAF1) cyclin-dependent kinase inhibitor regulates cell-cycle
      progression, senescence, and differentiation in injured blood vessels. Histone
      deacetylase (HDAC) inhibitors have shown utility in controlling proliferation in
      a wide range of tumor cell lines, possibly by inducing the expression of
      p21(WAF1). Our goal was to investigate the effect of trichostatin A (TSA), a
      specific and potent HDAC inhibitor, on the proliferation of vascular smooth
      muscle cells (VSMCs) isolated from rat thoracic aorta. TSA suppressed the HDAC
      activity of VSMCs in a dose-dependent manner and inhibited VSMC proliferation as
      demonstrated by cell number counting and the degree of [3H] thymidine
      incorporation. Further, TSA reduced the phosphorylation of Rb protein, a
      regulator of cell-cycle progression. TSA treatment also induced the expression of
      p21(WAF1) but not of p16(INK4), p27(KIP1) or p53. Finally, TSA inhibited HDAC
      activity of VSMCs from p21(WAF1) knock-out mice but had no effect on VSMC
      proliferation in these animals. In conclusion, TSA inhibits VSMC proliferation
      via the induction of p21(WAF1) expression and subsequent cell-cycle arrest with
      reduction of the phosphorylation of Rb protein at the G1-S phase.

PMID- 16908951
TI  - Thr-encoding allele homozygosity at codon 54 of FABP 2 gene may be associated
      with impaired delta 6 desatruase activity and reduced plasma arachidonic acid in
      obese children.
AB  - BACKGROUND: Alanine-for-threonine substitution at codon 54 (A54T polymorphism) in
      the fatty acid-binding protein 2 gene (FABP2) has been associated with
      hypertriglyceridemia and insulin resistance. Impairment in the activity of delta
      6 and 5 desaturases is also supposed to be a factor predisposing the development
      of insulin resistance syndrome. AIM: We investigated the relationship between
      A54T polymorphism in FABP2 and the impairment of long-chain polyunsaturated fatty
      acid metabolism in obese children. METHODS: Thirty-two obese children
      participated. During the study, the children continued their habitual diet, which
      was documented in a 3-day food record using household measures. Anthropometry was
      performed, and serum lipid and fatty acid composition in plasma were analyzed.
      The polymorphism of codon 54 in the FABP 2 gene was analyzed. RESULTS: The allele
      frequency was 0.66 and 0.34 for Ala54 and Thr54, respectively. There were no
      significant differences in age, body mass index, fasting serum glucose, insulin
      or serum lipoproteins among the three polymorphism groups. These were also no
      significant differences in the intake of energy, the percentage of energy
      nutrients or in the dietary lipid composition. The content of arachidonic acid
      (AA) in plasma was lowest in Thr/Thr54 (p < 0.05). The indices of delta-6
      desaturase (D6D) activity in Thr/Thr54 were significantly lower than in Thr/Ala54
      or Ala/Ala54 (p < 0.05, p < 0.01, respectively). CONCLUSIONS: In obese children,
      Thr/Thr54 of the FABP 2 gene is associated with impaired activation of D6D and
      reduced AA content. The results in the LCPUFA profile suggest that Thr/Thr54 may
      predispose the to development of insulin resistance.

PMID- 16908952
TI  - Effect of walking with a pedometer on serum lipid and adiponectin levels in
      Japanese middle-aged men.
AB  - OBJECTIVE: To clarify the effects of walking with a pedometer on metabolic
      parameters, including adiponectin (APN). METHODS: We recruited 44 male Japanese
      volunteers (age, 37 +/- 9 yrs; body mass index (BMI), 24.2 +/- 2.9 kg/m2; fasting
      plasma glucose (FPG), 96 +/- 11 mg/dL; total cholesterol (TC) 190 +/- 26 mg/dL;
      triglycerides (TG) 119 +/- 80 mg/dL; HDL-C56 +/- 14 mg/dL). Subjects were
      instructed to walk with a pedometer and record the number of steps they walked
      every day for 50 days. Serum adiponectin (APN) levels were measured by enzyme
      immunoassay. Treatment effects were examined by Wilcoxon's rank test. RESULTS:
      The average number of steps was 8211 +/- 2084 per day. There were significant
      reductions in BMI, sBP, TG and TNF-alpha levels after 50 days, but no changes in
      adiponectin levels. We then divided the subjects into 2 groups according to the
      steps walked per day, namely, more than 8000 steps (MT group, n = 22) and less
      than 8000 steps (LT group, n = 22) and found that the reduction in TG and BP was
      observed only in the MT group. CONCLUSIONS: Walking with a pedometer is effective
      for improving metabolic parameters, such as TG and blood pressure, but is not
      sufficient to increase adiponectin levels in Japanese men.

PMID- 16908953
TI  - Prevalence of metabolic syndrome in the general Japanese population in 2000.
AB  - To determine the prevalence of metabolic syndrome in the Japanese general
      population, we analyzed data from a nationwide survey conducted in 2000.
      According to the Japanese new diagnostic criteria for metabolic syndrome in 2005,
      we analyzed 3,264 people aged from 20 to 79 (men, 1,917; women, 1,347) from the
      total participants. The incidence of metabolic syndrome was 7.8%. Men had a
      higher incidence (12.1%) than women (1.7%). Most of the women satisfying the
      criteria were 50 years old or over, while the incidence in men started to rise
      from their 30s. When we applied the criteria of Adult Treatment Panel III, the
      incidence was about 3-fold higher. In this population visceral obesity was
      associated with metabolic abnormalities, such as higher LDL-cholesterol,
      triglyceride, glucose, and blood pressure and lower HDL-cholesterol. Thus we
      determined the incidence of metabolic syndrome and each metabolic abnormality in
      the Japanese general population in 2000 and found an association of visceral
      obesity with metabolic abnormalities. Intervention to reduce the incidence of
      metabolic syndrome in Japan is necessary to reduce the risk of cardiovascular
      disease.

PMID- 16908954
TI  - Analysis of the factors contributing to serum retinol binding protein and
      transthyretin levels in Japanese adults.
AB  - OBJECTIVE: We examined various factors possibly related to metabolic syndrome,
      particularly focusing on nutritional assessment proteins such as retinol binding
      protein (RBP) and transthyretin (TTR), and remnant lipoproteins. MATERIALS AND
      METHODS: Fasting serum lipid was analyzed in 58 Japanese adult volunteers (33 men
      and 25 women, 42.5 +/- 10.1 years old). RESULTS: The lipid profiles of the
      subjects were classified by lipoprotein polyacrylamide gel electrophoretic
      patterns into Types S (n = 10), A (n = 37), and N (n = 11), according to the
      method described in Internal Medicine 42: 244, 2003. RBP and TTR were
      significantly higher in Type N than in Types S and A. In multivariate analysis,
      RBP was accounted for by remnant-like particle-triglyceride (RLP-TG), interleukin
      6, body mass index and low-density lipoprotein (LDL)-cholesterol (adjusted R2 =
      0.621). TTR was accounted for by lipoprotein(a), adiponectin and RLP-TG (adjusted
      R2 = 0.415). Malondialdehyde-LDL was significantly accounted for by LDL
      cholesterol and RLP-cholesterol (adjusted R2 = 0.601). Lipoprotein(a) and LDL
      cholesterol were independent variables for oxidized LDL antigen (adjusted R2 =
      0.620). High-sensitivity C-reactive protein was accounted for by interleukin 6,
      immunoreactive insulin and oxidized LDL antigen (adjusted R2 = 0.361). Uric acid
      and body mass index were independent variables for adiponectin (adjusted R2 =
      0.429). CONCLUSION: RBP and TTR may be useful as convenient and simple clinical
      markers of overnutrition and possibly of metabolic syndrome.

PMID- 16908955
TI  - The anti-atherosclerotic effects of lipid lowering with atorvastatin in patients
      with hypercholesterolemia.
AB  - We investigated the lipid lowering and anti-atherosclerotic effects of
      atorvastatin in patients with hypercholesterolemia. Thirty patients were given
      atorvastatin 10 mg daily, and assessed for serum lipids, intima-media thickness
      (IMT), and brachial-ankle pulse wave velocity (ba-PWV) at the baseline, 6 months,
      and 12 months. Remnant-like particle-cholesterol (RLP-C), lipoprotein (a)(Lp(a)),
      and high-sensitivity C-reactive protein (hs-CRP) were measured in some patients
      at the baseline and at 6 months. Total cholesterol, triglyceride and low-density
      lipoprotein cholesterol were significantly decreased by 32%, 23% and 44% at 6
      months, respectively, and these effects were sustained at 12 months. There was no
      change in high-density lipoprotein cholesterol. IMT at the baseline was 0.88 +/-
      0.16 mm and decreased to 0.76 +/- 0.13 mm at 6 months, remaining at 0.75 +/- 0.12
      mm at 12 months. We did not observe any significant changes in ba-PWV. RLP-C and
      hs-CRP were significantly reduced from 7.3 +/- 10.8 mg/dL to 4.3 +/- 5.3 mg/dL
      and 0.075 +/- 0.065 mg/dL to 0.039 +/- 0.043 mg/dL at 6 months, respectively.
      There was no change in Lp(a). The observed decrease in IMT suggests that
      atorvastatin possibly improves atherosclerosis, in addition to the significant
      reduction of serum lipids.

PMID- 16908956
TI  - [A systematic review of working hours and mental health burden].
AB  - There is growing concern over the possible increase in mental health problems
      among Japanese workers. This trend is generally regarded as a reflection of
      Japan's prolonged economic depression and changes in working environment. In
      fact, claims for compensation for industrial accidents related to mental health
      diseases have been rapidly increasing in recent years. Working hours, personal
      relationships, support from supervisors/co-workers, job demand, job control, and
      payment are known to affect workers mental health. In 2004, the Government
      announced a guideline to combat overwork and mental health problems at work
      places. This guideline articulates that long overtime working is a major
      indicator, and workers who work over 100 h overtime in a month should be
      encouraged to see an occupational physician. This guideline takes into account
      the practicalities of occupational health at work places and the empiric
      knowledge that long working hours might associate with workers mental health
      status. It may be reasonable to assume that long working hours affect workers
      health status both psychologically and physiologically, interacting with a
      variety of occupational factors, particularly job stress. However, the
      association between working hours and workers mental health status has not been
      fully clarified. The present article aimed to provide a systematic review of the
      association between working hours and mental health problems. The authors
      conducted a systematic review of the published literature on the association
      between working hours and mental health problems using PubMed. Of 131 abstracts
      and citations reviewed, 17 studies met the predefined criteria. Ten of these are
      longitudinal studies, and the others are cross-sectional studies. Seven of the 17
      studies report statistically significant associations between working hours and
      mental health problems, while the others report no association. In addition,
      comparison among these studies is difficult because a variety of measurements of
      working hours were used. The present review found inconsistent results in the
      association between working hours and mental health burden.

PMID- 16908957
TI  - Morphological association between spermatophores and male genitalia in carabid
      beetles of the tribe Pterostichini (Coleoptera: Carabidae).
AB  - A morphological association between genitalia and ejaculates could provide
      insight into the function and evolution of genitalia. In this study, the
      morphologies of the ejaculates and male genitalia of 15 species of Pterostichini
      and two species of Platynini (Coleoptera: Carabidae) are described. All the
      species examined formed a spermatophore, the morphology of which could be
      classified into three types based on its relative volume in the female vaginal
      cavity and the presence or absence of a pluglike conformation. Male genital
      morphology could be divided into two types by the direction of the endophallus
      and gonopore. Species with a strongly bent endophallus invariably formed a
      pluglike spermatophore. The results suggest that the peculiar shape of
      endophallus found in some species of Pterostichini may function in forming the
      pluglike structure of the spermatophore.

PMID- 16908958
TI  - Occurrence of deformed fish and their fitness-related traits in Kirikuchi charr,
      Salvelinus leucomaenis japonicus, the southernmost population of the genus
      Salvelinus.
AB  - Kirikuchi charr, Salvelinus leucomaenis japonicus, is the southernmost population
      of the genus Salvelinus. It is endemic to the Kii Peninsula, central Honshu
      Island, Japan. As a consequence of anthropogenic disturbances, a few populations
      of Kirikuchi charr with low genetic diversity now survive only in small, isolated
      habitats. This study investigated the occurrence of deformed individuals and
      assessed differences between deformed and nondeformed fish in fitness-related
      traits, i.e., body size, body condition, growth rate, reproductive traits,
      survival rate, and habitat use, for two small isolated populations of Kirikuchi
      charr in the upper drainage of the Totsu River system of the Kii Peninsula. The
      two populations contained deformed fish in the respective proportions of 8.0
      17.4% and 3.0-5.8% between 2003 and 2005. Annual survival rates of deformed fish
      were approximately half those of nondeformed fish. Other traits were not
      significantly different between deformed and nondeformed fish. These results
      indicate that the occurrence of deformities is an important ecological indicator
      that reflects the decline in fitness of small, isolated populations.

PMID- 16908959
TI  - Isolation and characterization of two pigment-dispersing hormones from the
      whiteleg shrimp, Litopenaeus vannamei.
AB  - In crustaceans, the pigment-dispersing hormone (PDH) is released from the X
      organ/sinus gland complex located in the eyestalks, and controls pigment
      dispersion in the chromatophores. Knowledge concerning the structure and activity
      of PDH in penaeid shrimps is remains limited, since natural PDH has been purified
      from only the Kuruma prawn, Marsupenaeus japonicus. In this study, two PDHs (Liv
      PDH-A and -B) were purified from the sinus gland extracts of another penaeid
      species, the whiteleg shrimp, Litopenaeus vannamei, by two steps of reversed
      phase HPLC, and their amino acid sequences were determined. They both consist of
      18 amino acid residues, with a free N-terminus and an amidated C-terminus, the
      sequences of Liv-PDH-A and -B being NSELINSLLGIPKVMNDAamide and
      NSELINSLLGLPKVMNDAamide, respectively. These sequences are identical to those of
      mature PDHs deduced from cDNAs encoding L. vannamei PDH precursors cloned
      previously by other workers. Liv-PDH-A and -B showed significant pigment
      dispersing activity in melanophores by in vivo bioassay.

PMID- 16908960
TI  - Molecular characterization of the interferon-tau gene of the mithun (Bos
      frontalis).
AB  - The mithun (Bos frontalis) not only remains one of the most neglected ungulate
      species due to its remote range, but also has been identified as a vulnerable
      species due to its declining population. Augmenting its reproductive efficiency
      could be a strategy for reversing its population decline. Considering the
      importance of interferon-tau (IFNT) as a primary signal in establishing maternal
      recognition of pregnancy (MRP), the present study was undertaken to characterize
      the IFNT gene of the mithun. A 588 bp mithun IFNT (mitIFNT) gene was PCR
      amplified using genomic DNA as the template. Its nucleotide sequence comprised an
      entire open reading frame of 585 bp encoding a 195 amino acid pre-protein. In
      nucleotide sequence, the mitIFNT gene was more than 85% similar to the homologous
      genes of domestic and wild ruminant species characterized to date. However,
      phylogenetic analysis placed mitIFNT into a clade containing IFNT of the red
      deer, but not IFNTs of cow, sheep, or goats, or other wild ruminant species. Our
      characterization of mitIFNT represents the first complete sequence of any gene
      from the mithun.

PMID- 16908961
TI  - A CPG component LE generates depolarization of buccal neurons by producing
      constant plateau potentials during feeding responses of Aplysia kurodai.
AB  - In the buccal ganglia of Aplysia kurodai we have identified neurons (here termed
      LE neurons, or LE) producing plateau potentials lasting several seconds by
      application of short depolarizing currents. Results obtained from experiments
      using various bath solutions suggest that generation of these plateau potentials
      may be an endogenous property of LE. Application of various intensities or
      lengths of depolarizing currents induced in LE almost constant plateau potentials
      with fixed duration and depolarizing size. LE spikes produced monosynaptic EPSPs
      in the ipsilateral multi-action neuron (MA) and the jaw-closing motor neuron (JC)
      in the buccal ganglia. Conversely, MA spikes produced monosynaptic IPSPs in LE.
      There was electrical coupling between LE and both MA and JC. During the feeding
      like response elicited by electrical stimulation of the nerve, LE showed rhythmic
      depolarization almost simultaneously with MA and JC, and firing on the plateau
      potentials occurred during the period of JC firing, the later phase of radula
      retraction. Hyperpolarization of LE during the feeding-like response suppressed
      generation of plateau potentials, though rhythmic small depolarization was still
      induced. During LE hyperpolarization, the duration of the depolarization of MA
      and JC was shortened. These results suggest that LE may be an element of the
      feeding CPG circuit and may contribute to part of the depolarization of MA and JC
      by generating constant plateau potentials during the feeding response, though LE
      may not have rhythm-generating ability.

PMID- 16908962
TI  - NGIWYamide-induced contraction of tube feet and distribution of NGIWYamide-like
      immunoreactivity in nerves of the starfish Asterina pectinifera.
AB  - NGIWYamide, a neuropeptide recently isolated from sea cucumbers, was tested on
      tube feet of the starfish Asterina pectinifera. NGIWYamide (10(-6)-10(-4) M)
      caused contraction of isolated tube feet. NGIWYamide-like immunoreactivity
      (NGIWYa-LI) was investigated with an antiserum against NGIWYamide. NGIWYa-LI was
      found in the radial nerve cord (RNC), the marginal nerve, and the tube feet. Both
      ectoneural and hyponeural parts of the RNC showed NGIWYa-LI. Immunoreactive cell
      bodies were found in both parts of RNC. Extensive labeling in the basal region of
      the ectoneural part suggests that a substantial proportion of axons in this part
      contains NGIWYamide or a similar substance. In tube feet, NGIWYa-LI was found in
      the sub-epithelial nerve plexus and in the basal nerve ring. Double labeling
      along with 1E11, a neuron-specific monoclonal antibody developed from A.
      pectinifera, indicated that the structures with NGIWYa-LI are neurons. These
      results suggest that NGIWYamide or an NGIWYamide-like peptide exists in starfish
      and functions as a neurotransmitter or a neuromodulator.

PMID- 16908963
TI  - Development of a biotin-streptavidin amplified enzyme immunoassay for oxytocin
      and its application during milk ejection and the reproductive cycle in the mithun
      (Bos frontalis).
AB  - Oxytocin is a key hormone involved in milk ejection. It plays a key role in
      regulation of reproductive cyclicity in female mammals by taking part in the
      process of luteolysis. Determination of oxytocin is, therefore, important for
      studying the control of its secretion and its role in reproduction of the mithun.
      A simple and sufficiently sensitive enzyme immunoassay (EIA) for oxytocin
      determination in mithun plasma using the biotin-streptavidin amplification system
      and second antibody coating technique was therefore developed. Biotin was coupled
      to oxytocin and used to bridge between streptavidin-peroxidase and the
      immobilized oxytocin antiserum in a competitive assay. The EIA was conducted
      directly in 200 microl of unknown mithun plasma. Standards prepared in hormone
      free plasma were used. The lowest detection limit was 0.5 pg/ml plasma. Plasma
      volumes for the EIA (50, 100, and 200 microl) did not influence the shape of
      standard curve, even though a drop in OD450 was seen with higher plasma volumes.
      A parallelism test was carried out to compare endogenous mithun oxytocin with a
      bovine oxytocin standard. The former showed good parallelism with the bovine
      standard curve. For biological validation of the assay, plasma oxytocin was
      measured in the blood samples collected before, during, and after milking in
      three mithun cows and in six non-lactating cyclic mithuns during the entire
      estrous cycle. A sharp release of oxytocin shortly after udder stimulation was
      observed. A high level of oxytocin was maintained during milking, falling sharply
      thereafter. The mean plasma oxytocin concentration was different on different
      days of the estrous cycle (P < 0.001). Two peaks of oxytocin were recorded, one
      at day 6 and another at day 18 of the estrous cycle. In conclusion, a simple,
      sufficiently sensitive and direct EIA procedure has been developed for the first
      time to determine plasma oxytocin levels in mithuns. Apart from being non
      radioactive, the EIA procedure described here also utilizes a highly stable
      biotinalyted hormone which has a shelf life of several years, unlike the short
      shelf life of iodinated tracer used in RIA procedures.

PMID- 16908964
TI  - A new species of Thraulus from Nanjing (eastern China) with single first gill
      (Insecta: Ephemeroptera: Leptophlebiidae).
AB  - Thraulus femoratus sp. nov., a new species found in eastern China, is described
      from imagos, subimagos, nymphs, and eggs. The nymphs are unique in the genus as
      well as in the Thraulus group because of their single lanceolate gills 1. The
      imagos can be differentiated from those of related species by the following
      combination of characters: slightly robust hindwing with a bluntly rounded costal
      projection that is situated over half the distance from wing base to apex, darkly
      pigmented basal portion of hindwing, and subapical dark band on hind femur.
      Subimagos resemble the imagos in color pattern. Eggs have eight pairs of long
      threads on the polar portion and slight ridges on the surface. The reduced gills
      1 in combination with entirely fringed gills 2-7 represent a new evolutionary
      lineage and ecological type in the Thraulus group, but provide limited
      information regarding phylogenetic relationships.

PMID- 16908965
TI  - A new cascade frog of the subgenus Odorrana from peninsular Malaysia.
AB  - We describe a new species of cascade frog of the genus Rana, from west Malaysia.
      Rana monjerai, new species is a medium-sized frog of the subgenus Odorrana (SVL
      of males, 38-43 mm; of one female, 75 mm), and is distinguished from all other
      members of this subgenus by the combination of: white lip stripe, dorsolateral
      fold, full web on the fourth toe, vomerine teeth, gular vocal pouch and
      relatively large tympanum in males, no dorsal marking, no clear light spots on
      rear of thigh, first finger subequal to second, finely tuberculated dorsum, and
      unpigmented ova. The significance of finding this species from peninsular
      Malaysia is discussed.

PMID- 16908966
TI  - Williamsocoris, a new genus of Schizopteridae (Heteroptera) from Argentina.
AB  - A new genus and species, Williamsocoris ornatus (Schizopteridae:
      Hypselosomatinae), is described from Argentina. This is the first record of the
      subfamily in South America. The particular structures of the rostrum of this new
      taxon are unique in the family.

PMID- 16908968
TI  - The long processes of short interfering RNAs--RNA interference and its
      implications in neuronal cells.
AB  - Reverse genetics has been greatly advanced by the discovery of RNA interference
      (RNAi). This intracellular RNA-mediated gene silencing pathway is partially
      conserved from plants to mammals and offers a new powerful tool for the analysis
      of gene function. We give a brief overview of the discovery of RNAi, the
      underlying mechanisms and probable intrinsic roles of the pathway. Recent reports
      utilizing RNAi for gene silencing approaches in neuronal cells are reviewed and
      possible delivery techniques for small interfering RNA/double-stranded RNA are
      discussed.

PMID- 16908969
TI  - Neuronal apoptosis in neurodegenerative diseases: from basic research to clinical
      application.
AB  - In recent years, the investigation of erroneous regulation of apoptotic
      mechanisms during acute and chronic injury of neuronal cells has gained
      increasing attention. Besides acute neuronal trauma and ischemia, chronic
      neurodegenerative diseases like Alzheimer's, Huntington's, Parkinson's and Lou
      Gehrig's disease (amyotrophic lateral sclerosis) are of particular interest. The
      present article will provide an overview of basic apoptotic mechanisms, the
      contribution of neuronal apoptosis to the above-mentioned disorders, potential
      clinical applications and their limitations and the possible implications for
      future studies regarding these neurodegenerative diseases.

PMID- 16908970
TI  - Active immunization of mice with an Abeta-Hsp70 vaccine.
AB  - Heat-shock proteins are highly immunogenic. Complexed with an antigen, they act
      as adjuvants, inducing a humoral and cellular immune response against both the
      antigen and the chaperone. In this study, we produced an Hsp70-supported vaccine
      to induce the generation of antibodies against amyloid-beta (Abeta) peptides, the
      major constituent of beta-amyloid plaques in Alzheimer's disease. The vaccine
      consisted of synthetic human Abeta42 covalently cross-linked with DnaK, an Hsp70
      homolog of Escherichia coli. Active immunization of mice with this vaccine
      resulted in the generation of antibodies against Abeta, that were detectable in
      sera after the first booster immunization. Antibody titers varied markedly with
      the genetic background of the mice. Prophylactic short-term immunization of
      transgenic mice (APP tg2576) before the onset of plaques, however, did not
      prevent amyloid plaque deposition. There were no differences in the plaque load
      and in the level of Triton X-100-soluble Abeta peptides in the brains of
      immunized and control-treated transgenic mice. Unexpectedly, the level of formic
      acid soluble Abeta peptides tended to be higher in immunized mice. The reason for
      the increase may be an enhanced deposition of Abeta in the small cerebral blood
      vessels. These data emphasize the need for anti-Abeta antibodies that remove
      Abeta peptides from the central nervous system without negative side effects.

PMID- 16908971
TI  - Hypocapnia induces caspase-3 activation and increases Abeta production.
AB  - BACKGROUND: At least half of all cases of early onset (<60) familial Alzheimer's
      disease (FAD) are caused by any of over 150 mutations in three genes: the amyloid
      precursor protein (APP), presenilin 1 (PS1), and presenilin 2 (PS2). Mutant forms
      of PS1 have been shown to sensitize cells to apoptotic cell death. OBJECTIVE: We
      investigated the effects of hypocapnia, a risk factor for both cognitive and
      neurodevelopment deficits, on caspase-3 activation, apoptosis, and amyloid beta
      protein (Abeta) production, and assessed the influence of the PS1Delta9 FAD
      mutation on these effects. METHOD: For this purpose, we exposed stably
      transfected H4 human neuroglioma cells to conditions consistent with hypocapnia
      (PCO2<40 mm Hg) and hypocapnia plus hypoxia (PO2<21%). RESULTS: Hypocapnia (20 mm
      Hg CO2 for 6 h) induced caspase-3 activation and apoptosis; the PS1Delta9 FAD
      mutation significantly potentiated these effects. Moreover, the combination of
      hypocapnia (20 mm Hg CO2) and hypoxia (5%O2) induced caspase-3 activation and
      apoptosis in a synergistic manner. Hypocapnia (5 and 20 mm Hg CO2 for 6 h) also
      led to an increased Abeta production. CONCLUSION: The findings suggest that
      hypocapnia (e.g. during general anesthesia) could exacerbate AD
      neuropathogenesis.

PMID- 16908972
TI  - Beta-amyloid treatment sensitizes mice to amphetamine-induced locomotion but
      reduces response to caffeine.
AB  - BACKGROUND: Psychosis frequently occurs in Alzheimer's disease (AD), being
      associated with more severe cognitive decline, but the underlying mechanisms are
      unknown. OBJECTIVE: To investigate the effect of centrally administered beta
      amyloid peptide, a model for AD, in the locomotor response to amphetamine,
      caffeine and MK-801, which are psychoactive drugs related to neurochemical
      changes occurring in psychosis. METHODS: Mice were intracerebroventricularly
      injected with beta-amyloid (25-35), and after 1 week they were tested in the
      passive avoidance, spontaneous alternation and locomotor tasks. RESULTS: Besides
      impaired performance in inhibitory avoidance and spontaneous alternation tasks,
      beta-amyloid-treated mice showed increased spontaneous locomotion, augmented
      response to amphetamine (1.5 mg/kg), blunted response to caffeine (30 mg/kg) and
      no difference in MK-801 (0.25 mg/kg)-induced locomotor activation when compared
      to its respective control. CONCLUSION: These results are compatible with the
      hypothesis that beta-amyloid peptide may predispose to psychotic symptoms of AD
      by increasing sensitivity of the dopaminergic system, possibly related to a
      decreased adenosinergic inhibitory tone.

PMID- 16908974
TI  - List of drugs in development for neurodegenerative diseases.

PMID- 16908973
TI  - The TAT protein transduction domain enhances the neuroprotective effect of glial
      cell-line-derived neurotrophic factor after optic nerve transection.
AB  - Glial-cell-line-derived neurotrophic factor (GDNF) acts as a potent survival
      factor for many neuronal populations, including retinal ganglion cells (RGC),
      indicating a potential therapeutic role of GDNF for neurological disorders. To
      enhance the tissue distribution and applicability of the neurotrophin, we linked
      it to a protein transduction domain derived from the HIV TAT protein and tested
      it in a well-established model for traumatic injury in the CNS: After optic nerve
      axotomy, the number of surviving RGCs was significantly increased in mice
      injected with TAT-GDNF on days 0, 3, 7, and 10 after surgery compared with GDNF-
      or PBS-injected animals. Moreover, TAT-GDNF reduced the number of activated
      caspase-3-positive cells. These results show that the neuroprotective effect of
      substances like neurotrophins may be enhanced by linking them to a domain that
      has been shown to mediate efficient transduction across biological membranes.

PMID- 16908975
TI  - Mitochondria in amyotrophic lateral sclerosis: a trigger and a target.
AB  - Strong evidence shows that mitochondrial dysfunction is involved in amyotrophic
      lateral sclerosis (ALS), but despite the fact that mitochondria play a central
      role in excitotoxicity, oxidative stress and apoptosis, the intimate underlying
      mechanism linking mitochondrial defects to motor neuron degeneration in ALS still
      remains elusive. Morphological and functional abnormalities occur in mitochondria
      in ALS patients and related animal models, although their exact nature and extent
      are controversial. Recent studies postulate that the mislocalization in
      mitochondria of mutant forms of copper-zinc superoxide dismutase (SOD1), the only
      well-documented cause of familial ALS, may account for the toxic gain of function
      of the enzyme, and hence induce motor neuron death. On the other hand,
      mitochondrial dysfunction in ALS does not seem to be restricted only to motor
      neurons as it is also present in other tissues, particularly the skeletal muscle.
      The presence of this 'systemic' defect in energy metabolism associated with the
      disease is supported in skeletal muscle tissue by impaired mitochondrial
      respiration and overexpression of uncoupling protein 3. In addition, the lifespan
      of transgenic mutant SOD1 mice is increased by a highly energetic diet
      compensating both the metabolic defect and the motorneuronal function. In this
      review, we will focus on the mitochondrial dysfunction linked to ALS and the
      cause-and-effect relationships between mitochondria and the pathological
      mechanisms thought to be involved in the disease.

PMID- 16908976
TI  - Influence of different promoters on the expression pattern of mutated human alpha
      synuclein in transgenic mice.
AB  - Two missense mutations (A53T and A30P) in the gene encoding the presynaptic
      protein alpha-synuclein (asyn) are associated with rare, dominantly inherited
      forms of Parkinson's disease (PD) and its accumulation in Lewy bodies and Lewy
      neurites. As an initial step in investigating the role of asyn in the
      pathogenesis of PD, we have generated C57BL/6 transgenic mice overexpressing the
      doubly mutated human asyn under the control of three different promoters; the
      chicken beta-actin (chbetaactin), the mouse tyrosine hydroxylase 9.6 kb (msTH)
      and the mouse prion protein (msprp). In this study we compared the regional and
      cellular expression pattern of the transgenic protein in the brain and peripheral
      organs of various transgenic mouse lines. Western blot analysis and
      immunohistochemistry consistently showed that all three promoters successfully
      drive the expression of the transgene. The msprp promoter was found to give the
      highest level of transgene expression. All promoters directed the expression into
      the brain and specific neuron types. However, the promoters differed with respect
      to (i) the expression pattern in peripheral organs, (ii) the number and (iii) the
      regional distribution of expressing cells in the brain. Furthermore, remarkable
      line-to-line variation of expression patterns was observed in mouse lines
      carrying the same construct. Future studies will analyze how the variations in
      transgene expression affect the pathogenesis in the animals.

PMID- 16908978
TI  - List of drugs in development for neurodegenerative diseases. Update March 2005.

PMID- 16908977
TI  - Unchanged scrapie pathology in brain tissue of tyrosine kinase Fyn-deficient
      mice.
AB  - Fyn is a 59-kDa member of the Src family of tyrosine kinases synthesized on
      cytosolic polysomes and then targeted to the plasma membrane where it clusters in
      caveolae-like membrane microdomains. The cellular isoform of the prion protein
      (PrP) has also been identified to be a caveolar constituent and to participate in
      signal transduction events concerning cell survival and differentiation via
      recruitment of Fyn. We studied the scrapie infection of mice deficient for Fyn
      (Fyn(-/-)) to clarify the role of Fyn in an in vivo model of transmissible
      spongiforme encephalopathies. Fyn(-/-) mice died on average 9 days earlier than
      wild-type control mice, but no differences were seen regarding activation of
      astrocytes, vacuolization of the neuropil, and accumulation of misfolded prion
      protein. The experimental model suggests that a deficiency for Fyn is detrimental
      in prion diseases, although it has no major effect on the clinical course of an
      experimental prion infection of the CNS.

PMID- 16908979
TI  - The role of ubiquitin-protein ligases in neurodegenerative disease.
AB  - Alzheimer's disease and Parkinson's disease are the most common neurodegenerative
      conditions associated with the ageing process. The pathology of these and other
      neurodegenerative disorders, including polyglutamine diseases, is characterised
      by the presence of inclusion bodies in brain tissue of affected patients. In
      general, these inclusion bodies consist of insoluble, unfolded proteins that are
      commonly tagged with the small protein, ubiquitin. Covalent tagging of proteins
      with chains of ubiquitin generally targets them for degradation. Indeed, the
      ubiquitin/proteasome system (UPS) is the major route through which intracellular
      proteolysis is regulated. This strongly implicates the UPS in these disease
      associated inclusions, either due to malfunction (of specific UPS components) or
      overload of the system (due to aggregation of unfolded/mutant proteins),
      resulting in subsequent cellular toxicity. Protein targeting for degradation is a
      highly regulated process. It relies on transfer of ubiquitin molecules to the
      target protein via an enzyme cascade and specific recognition of a substrate
      protein by ubiquitin-protein ligases (E3s). Recent advances in our knowledge
      gained from the Human Genome Mapping Project have revealed the presence of
      potentially hundreds of E3s within the human genome. The discovery that parkin,
      mutations in which are found in at least 50% of patients with autosomal recessive
      juvenile parkinsonism, is an E3 further highlights the importance of the UPS in
      neurological disease. To date, parkin is the only E3 confirmed to have a direct
      causal role in neurodegenerative disorders. However, a number of other (putative)
      E3s have now been identified that may cause disease directly or interact with
      neurological disease-associated proteins. Many of these are either lost or
      mutated in a given disease or fail to process disease-associated mutant proteins
      correctly. In this review, we will discuss the role(s) of E3s in
      neurodegenerative disorders.

PMID- 16908980
TI  - Neurotrophic factors and amyotrophic lateral sclerosis.
AB  - The cause of motor neuron death in amyotrophic lateral sclerosis (ALS) remains a
      mystery. Initial implications of neurotrophic factor impairment involved in
      disease progression causing selective motor neuron death were brought forward in
      the late 1980s. These implications were based on several in vitro studies of
      motor neuron cultures in which a near to complete rescue of axotomized neonatal
      motor neurons in the presence of supplementary neurotrophic factors were
      revealed. These findings pawed the way for extensive investigations in
      experimental animal models of ALS. Neurotrophic factor administration in rodent
      ALS models demonstrated a remarkable effect on survival of degenerating motor
      neurons and rescue of axotomized motor neurons, both in vivo and in vitro. In the
      absence of efficient therapy for ALS, some of these promising neurotrophic
      factors have been administered to groups of ALS patients, as they appeared
      available for clinical trials. Up to date, none of tested factors has lived up to
      expectations, altering the outcome of the disease. This review summarizes current
      findings on neurotrophic factor expression in ALS tissue and these factors'
      potential/debatable clinical relevance to ALS and the treatment of ALS. It also
      discusses possible interventions improving clinical trial design to obtain
      efficacy of neurotrophic factor treatment in patients suffering from ALS.

PMID- 16908981
TI  - A non-viral vector for targeting gene therapy to motoneurons in the CNS.
AB  - Gene therapy vectors that can be targeted to motoneuronal cells are required in
      the field of neurodegenerative diseases. We propose the use of the atoxic
      fragment C of tetanus toxin (TTC) as biological activity carrier to the
      motoneurons. Naked DNA encoding beta-galactosidase-TTC hybrid protein was used to
      transfect muscle cells in vivo, resulting in a selective gene transfer of the
      enzymatic activity to the CNS. In the muscle, level expression of beta
      galactosidase was readily detectable 24 h after injection, reaching a maximum
      after 4 days and gradually decreasing thereafter. Labelling in the hypoglossal
      motoneurons and motor cortex was observed from 4 days after injection. In this
      paper, we show that TTC works as an enzymatic activity carrier to the CNS when
      muscle cells are transfected in vivo. We have also shown that the presence of TTC
      does not have any influence on the expression of the transfected gene. Both these
      results warrant further studies of TTC as a means of treating motoneuron diseases
      in the field of gene therapy.

PMID- 16908982
TI  - Changes in dopamine D2 receptors and 6-[18F]fluoro-L-3,4-dihydroxyphenylalanine
      uptake in the brain of 6-hydroxydopamine-lesioned rats.
AB  - We studied tracer distributions in positron emission tomography of ligands for
      dopamine D1 receptors ([11C]SCH23390) and D2 receptors ([11C]raclopride) and the
      dopamine precursor analog 6-[18F]fluoro-L-3,4-dihydroxyphenylalanine
      ([18F]FDOPA), as a measurement of presynaptic dopaminergic function, in the brain
      after 6-hydroxydopamine lesioning of the medial forebrain bundle in rats. The
      unilateral lesions were confirmed behaviorally by methamphetamine-induced
      rotation 2 weeks after lesioning, and the brains were analyzed by tissue
      dissection following an intravenous bolus of each tracer 3 weeks after lesioning.
      [11C]Raclopride, but not [11C]SCH23390, showed a higher accumulation in the
      striatum on the lesion side compared with that on the non-lesioned (intact) side.
      On the other hand, a lower accumulation of [18F]FDOPA was found in the striatum
      and cerebral cortex on the lesion side. Our studies demonstrate upregulation of
      dopamine D2 receptors in the striatum and a decrease in FDOPA uptake in both the
      striatum and cerebral cortex ipsilateral to the 6-hydroxydopamine lesions.
      Therefore, the combination of a D2 antagonist and FDOPA may provide a potentially
      useful method for assessing the effects of dopamine depletion in Parkinson's
      disease.

PMID- 16908983
TI  - List of drugs in development for neurodegenerative diseases. Update June 2004.

PMID- 16908985
TI  - Assessment of the bioactivity of antibodies against beta-amyloid peptide in vitro
      and in vivo.
AB  - The accumulation of the beta-amyloid peptide (Abeta) is a central event in the
      pathogenesis of Alzheimer's disease (AD). Abeta removal from the brain by immune
      therapy shows promising potential for the treatment of patients with AD, although
      the mechanisms of the antibody action are incompletely understood. In this study
      we compared the biological activities of antibodies raised against various Abeta
      fragments for Abeta reduction in vitro and in vivo. Antibodies against Abeta
      enhanced the uptake of Abeta42 aggregates up to 6-fold by primary microglial
      cells in vitro. The kinetics of Abeta42 uptake varied considerably among
      antibodies. Based on the activity to mediate Abeta42 uptake by microglial cells,
      we identified a bioactive antibody that significantly reduced Abeta42 levels in
      the brains of transgenic mice with neuronal expression of an AD-related mutated
      amyloid precursor protein. This effect depended on the epitopes recognized by the
      antibody. Our data suggest that the ability to facilitate Abeta42 uptake by
      primary microglia cells in vitro can be used to predict the biological activity
      of the antibody by passive immunization in vivo. This protocol may prove useful
      for the rapid validation of the activity of antibodies designed to be used in
      immune therapy of AD.

PMID- 16908986
TI  - BACE1 and presenilin: two unusual aspartyl proteases involved in Alzheimer's
      disease.
AB  - Two enzymatic activities are required to generate the pathogenic beta-amyloid
      (Abeta) peptide that accumulates in the brain of Alzheimer's disease patients.
      Both activities are carried out by two unusual aspartyl proteases known as beta-
      and gamma-secretase. Their therapeutic inhibition appears, therefore, a promising
      strategy to treat the disease. Transgenic mouse models in which the genes
      encoding the secretases have been ablated offer an invaluable tool, on the one
      hand, to gain more insights into the biological function of these proteases and,
      on the other hand, to predict the consequences that might be associated with
      enzyme inhibition in vivo.

PMID- 16908987
TI  - Caenorhabditis elegans MPP+ model of Parkinson's disease for high-throughput drug
      screenings.
AB  - The neurotoxin MPTP and its active metabolite MPP+ cause Parkinson's disease (PD)
      like symptoms in vertebrates by selectively destroying dopaminergic neurons in
      the substantia nigra. MPTP/MPP+ models have been established in rodents to screen
      for pharmacologically active compounds. In addition to being costly and time
      consuming, these animal models are not suitable for large scale testings using
      compound libraries. We present a novel MPP+-based model for high-throughput
      screenings using the nematode Caenorhabditis elegans. Incubation of C. elegans
      with MPTP or its active metabolite MPP+ resulted in strong symptomatic defects
      including reduced mobility and increased lethality, and is correlated with a
      specific degeneration of the dopaminergic neurons. The phenotypic consequences of
      MPTP/MPP+ treatments were recorded using automated hardware and software for
      quantification. Incubation of C. elegans with a variety of pharmacologically
      active components used in PD treatment reduced the MPP+-induced defects. Our data
      suggest that the C. elegans MPTP/MPP+ model can be used for the quantitative
      evaluation of anti-PD drugs.

PMID- 16908988
TI  - Presenilin 1 and cadherins: stabilization of cell-cell adhesion and proteolysis
      dependent regulation of transcription.
AB  - Presenilin-1 (PS1) has gained intensive attention in relation to Alzheimer's
      disease, since it has been shown that PS1 mutations are linked to familial
      Alzheimer's disease (FAD), and that PS1 is a member of the high molecular weight
      complex of gamma-secretase, which generates the carboxyl end of beta-amyloid
      peptide (gamma-cleavage). A parallel line of evidence suggests that upon
      formation of cell-cell contacts, presenilin colocalizes with cadherins at the
      cell surface and stabilizes the cadherin-based adhesion complex. Under conditions
      stimulating cell-cell dissociation, cadherins are processed by a PS1/gamma
      secretase activity, promoting disassembly of adherens junctions, and resulting in
      the increase of cytosolic beta-catenin, which is an important regulator of the
      Wnt/Wingless signaling pathway. PS1 also controls the cleavage of a number of
      transmembrane proteins at the interface of their transmembrane and cytosolic
      domains (epsilon-cleavage), producing intracellular fragments with a putative
      transcriptional role. Remarkably, cleavage of N-cadherin by PS1 produces an
      intracellular fragment that downregulates CREB-mediated transcription, indicating
      a role of PS1 in gene expression. PS1 mutations associated with FAD abolish
      production of the N-cadherin intracellular fragment and thus fail to suppress
      CREB-dependent transcription. These findings suggest an alternative explanation
      for FAD that is separate from the widely accepted 'amyloid hypothesis':
      dysfunction in transcription regulatory mechanisms.

PMID- 16908989
TI  - The biochemical and genetic odyssey to the function of a nicastrin-like protein.
AB  - Gamma-secretase is a high-molecular-weight protein complex required for the
      proteolytic processing of various transmembrane proteins including the
      Alzheimer's disease-associated amyloid precursor protein and the signaling
      receptor Notch. One of the gamma-secretase complex components is the type I
      transmembrane protein nicastrin. Here we review the odyssey to a cyclopic fish,
      which at the end allowed the functional analysis of nicalin, a novel member of
      the nicastrin protein family. This 60-kDa protein is part of a previously unknown
      membrane protein complex unrelated to gamma-secretase and binds to Nomo (Nodal
      modulator, previously known as pM5), a novel 130-kDa transmembrane protein. Both
      proteins are highly conserved in metazoans and show almost identical tissue
      distribution in humans. Functional studies in zebrafish embryos and cultured
      human cells revealed that nicalin and Nomo collaborate to antagonize the
      Nodal/TGFbeta signaling pathway. Thus, nicastrin and nicalin are both associated
      with protein complexes involved in cell fate decisions during early embryonic
      development.

PMID- 16908990
TI  - A model system to study intracellular trafficking and processing of the
      Alzheimer's amyloid precursor protein.
AB  - The occurrence of consensus phosphorylation sites in the intracellular domain of
      the Alzheimer's amyloid precursor protein (APP), coupled with observations of
      their in vivo phosphorylation, prompted several workers to investigate the
      effects that phosphorylation of such sites could have on APP metabolism and
      subsequent Abeta production. However, hitherto all attempts to dissect the role
      played by such phosphorylation events failed to reveal substantial effects.
      Having decided to revisit this problem, our new approach was based on the
      following vectors: (1) site-directed mutagenesis of the target amino acids to
      mimic a specific phosphorylation state, (2) expression of wild-type and mutant
      APP-GFP (green fluorescent protein) fusion proteins for ease of visualization,
      (3) controlled low level expression to avoid 'flooding' cellular pathways, and
      (4) the use of cycloheximide to inhibit de novo protein synthesis. Using this
      method we were able to detect specific differences in APP processing that were
      correlated with the mimicked phosphorylation state of several phosphorylation
      sites. New combined methodologies, like the one described here, allow for the
      detailed analysis of key control points in the cellular metabolism of specific
      proteins that are central to neurodegenerative diseases and may be under the
      control of specific posttranslational modifications, such as reversible
      phosphorylation.

PMID- 16908991
TI  - Plasmin deficiency in Alzheimer's disease brains: causal or casual?
AB  - Substantial recent evidence suggests that defects in amyloid peptide degradation
      can be at the base of cases of sporadic Alzheimer's disease (AD). Among the
      discovered brain enzymes with the capacity to degrade amyloid peptide, the serine
      protease plasmin acquires special physiological relevance because of its low
      levels in areas of AD human brains with a high susceptibility to amyloid plaque
      accumulation. In this article we comment on a series of observations supporting
      the fact that plasmin paucity in the brain is not simply a secondary event in the
      disease but rather a primary defect in certain cases of sporadic AD. We also
      refer to recent data pointing to alterations in raft membrane domains and
      diminished membrane cholesterol as the underlying cause. Finally, we discuss the
      possibility that plasmin deficiency in the brain could lead to AD symptomatology
      because of amyloid aggregation and the triggering of cell death signaling
      cascades.

PMID- 16908992
TI  - Problems and solutions in the genetic analysis of late-onset Alzheimer's disease.
AB  - The identification of the apolipoprotein E gene as a risk factor for late-onset
      Alzheimer's disease was a spectacularly successful application of genetic
      analysis to a complex trait, and it led to the hope and expectation that other
      risk loci for the disease would soon be forthcoming. Twelve years later, despite
      a huge amount of work, no other loci have been identified. In this article, we
      discuss the complexity of the problem and the pitfalls in the analytical methods
      that have been used and how we are approaching this problem.

PMID- 16908993
TI  - Clinical and molecular aspects of frontotemporal dementia.
AB  - Frontotemporal dementia (FTD) is a neurodegenerative disease and next to
      Alzheimer's disease and vascular dementia, the third most common cause of early
      onset progressive dementia. FTD leads to neurodegeneration in the frontal and
      temporal neocortex and usually encompasses both sides of the frontal and anterior
      temporal lobes. Psychologically, FTD is characterized by personality changes such
      as lack of insight, inappropriate behaviour, disinhibition, apathy, executive
      disabilities and a decline in cognitive functions, with large clinical and
      neuropathological variations among cases. Neuropathological characteristics
      include gliosis or microvacuolation of cortical nerve cells. Inclusions staining
      for tau protein and/or ubiquitin are also common findings. Both sporadic and
      hereditary forms of FTD have been identified and 30-50% of the FTD cases have a
      familial background. So far, at least three genetic loci for FTD have been
      identified, at human chromosomes 3, 9 and 17 in familial forms of the disease. A
      large number of the familial forms have been linked to chromosome 17q21 and
      referred to as frontotemporal dementia and Parkinsonism linked to chromosome 17.
      In the majority of these families, pathogenic mutations in the tau gene were
      identified. However, tau mutations seem to be a rare cause of disease in the
      general FTD population. Thus, other genes and/or environmental factors are yet to
      be identified, which will give further clues to this complex and heterogeneous
      disorder.

PMID- 16908994
TI  - Voxel-based morphometry in tau-positive and tau-negative frontotemporal lobar
      degenerations.
AB  - BACKGROUND: The identification of specific, diagnostically useful predictors of
      protein dysfunction in the frontotemporal lobar degenerations (FTLD) is a problem
      of great clinical and biological interest. Correlations between regional patterns
      of tissue loss and specific proteinopathies have not been established. OBJECTIVE:
      Specific brain imaging correlates of protein tau dysfunction were sought using
      voxel-based morphometry in FTLD subgroups with and without tau pathology.
      METHODS: Seventeen patients with pathologically or genetically confirmed
      diagnoses of FTLD who had undergone volumetric brain magnetic resonance imaging
      (MRI) were identified retrospectively and tau-positive (n = 9) and tau-negative
      (n = 8) subgroups were defined. MRI data were compared with healthy age- and sex
      matched controls using voxel-based morphometry implemented in a statistical
      parametric mapping software package. RESULTS: Compared with controls, tau
      positive and tau-negative subgroups had extensive common areas of regional brain
      atrophy predominantly affecting the frontal and anterior temporal lobes. No
      specific brain imaging features were identified for either subgroup. CONCLUSION:
      Patterns of frontotemporal atrophy do not predict the presence or absence of tau
      pathology; conversely, different immunohistochemical profiles are associated with
      similar patterns of regional vulnerability to neuronal loss in FTLD.

PMID- 16908995
TI  - Cerebrospinal fluid profile of amyloid beta peptides in patients with Alzheimer's
      disease determined by protein biochip technology.
AB  - Amyloid-beta peptides (Abeta) are major components of amyloid plaques in the
      Alzheimer's disease (AD) brain and have been proposed as diagnostic markers in
      cerebrospinal fluid (CSF). Abeta derived from brain may be processed into
      fragments before emerging in CSF. Therefore, we determined mass profiles of Abeta
      peptides in CSF of patients with AD and age-matched healthy control subjects
      (CTR) by using protein biochip technology. Abeta peptides were captured on the
      chip surfaces (spots) by the specific monoclonal antibody 6E10 and were then
      analyzed by integrated surface-enhanced laser desorption and ionization time-of
      flight mass spectrometry (SELDI-TOF-MS). We found Abeta species with mean
      molecular masses at 1,583.3 Da (corresponding to Abeta2-14), 2,068.5 Da (Abeta1
      17), 2,166.4 Da (Abeta1-18), 3,676.6 Da (Abeta1-33), 3,789.4 Da (Abeta1-34),
      4,076.9 Da (Abeta1-37), 4,134.0 Da (Abeta1-38), 4,233.3 Da (Abeta1-39), 4,332.4
      Da (Abeta1-40) and 4,516.8 Da (Abeta1-42) in both AD (n = 24) and CTR (n = 24)
      subjects. Abeta1-38 appeared to be a major Abeta species in human CSF along with
      Abeta1-40. Quantitation revealed that CSF levels of Abeta1-38 were significantly
      decreased in AD as compared to CTR subjects. The CSF profile of Abeta peptides
      may be used for diagnostic and therapeutic purposes in clinical studies.

PMID- 16908996
TI  - Lithium decreases secretion of Abeta1-42 and C-truncated species Abeta1
      37/38/39/40 in chicken telencephalic cultures but specifically increases
      intracellular Abeta1-38.
AB  - We studied endogenous amyloid precursor protein (APP) processing and amyloid beta
      (Abeta) peptide formation in primary chicken telencephalic neurons, because their
      Abeta peptide sequence is identical to humans. As detected by quantitative Abeta
      SDS-PAGE/immunoblot, Abeta peptides 1-40/42 and three additional C-truncated
      species, namely Abeta1-37/38/39 were regularly released into the supernatant. The
      highly conserved Abeta quintet strongly resembles the pattern of Abeta peptides
      found in human cerebrospinal fluid. Furthermore, the C-terminally shorter Abeta
      peptides 1-33/34 could be readily detected. Recent evidence indicates that
      lithium specifically inhibits secretion of the amyloidogenic Abeta1-42 peptide in
      cultured permanent cells transfected with human APP. We therefore investigated
      the effect of lithium on Abeta peptide secretion as well as intracellular Abeta
      peptides in our untransfected primary cell culture system. Our data shows that
      lithium leads to a dose-dependent reduction of Abeta1-37/38/39/40/42 secretion.
      Surprisingly, intracellular analysis revealed that lithium specifically increases
      a band comigrating with synthetic Abeta1-38 while Abeta1-40 and Abeta1-42
      remained almost unaffected. These results demonstrate for the first time that
      lithium treatment decreases Abeta peptide secretion in primary chicken neuronal
      cells but specifically elevates intracellular Abeta1-38. Therefore, we conclude
      that there are two independent mechanisms of lithium in intra- and extracellular
      Abeta peptide production.

PMID- 16908997
TI  - Reconstructing prions: fibril assembly from simple yeast to complex mammals.
AB  - With the epizootics of bovine spongiform encephalopathy (BSE) in North American
      cattle, BSE infections in goats, new forms of human Creutzfeldt-Jakob disease
      (CJD) and the spread of chronic wasting disease in North American deer and elk,
      one wonders whether we are gaining control over the transmissible spongiform
      encephalopathies (TSEs). Although many basic scientific questions in the prion
      field remain hotly debated and unresolved [1], including the function of the
      cellular prion protein (PrP), light has been shed on a diverse array of topics,
      and discussions at the latest TSE meeting ranged broadly from yeast prion fibril
      assembly to mammalian prion neurotoxicity to future TSE therapies. Prion diseases
      are protein misfolding disorders which cause degeneration of the central nervous
      system (CNS) and ultimately death. The unique and surprising feature is that
      prion diseases are infectious. Yeast prions are derived from proteins differing
      from the mammalian PrP but are also infectious, self propagating proteins which
      typically can convert into an aggregated, amyloidogenic form having high beta
      sheet content. The simple yeast organism has served as a valuable model for
      understanding aspects of prion biology, such as prion fibril assembly.

PMID- 16908998
TI  - Hippocampal spatial memory impairments caused by the familial Alzheimer's disease
      linked presenilin 1 M146V mutation.
AB  - Mutations in presenilins (PS) 1 and 2 are the major cause of familial Alzheimer's
      disease. Conditional inactivation of PS1 in the mouse postnatal forebrain leads
      to mild deficits in spatial learning and memory, whereas inactivation of both PS1
      and PS2 results in severe memory and synaptic plasticity impairments, followed by
      progressive and substantial neurodegeneration. Here we investigate the effect of
      a familial Alzheimer's disease-linked PS1 missense mutation using knock-in (KI)
      mice, in which the wild-type PS1 allele is replaced with the M146V mutant allele.
      In the Morris water maze task, PS1 KI mice at 3 months of age exhibit reduced
      quadrant occupancy and platform crossing in the probe trial after 6 days of
      training, though their performance was normal in the probe trial after 12 days of
      training. By the age of 9 months, even after 12 days of training, PS1 homozygous
      KI mice still exhibit reduced platform crossing in the post-training probe trial.
      ELISA analysis revealed a selective increase in cortical levels of beta-amyloid
      42 in PS1 KI mice, whereas production of beta-amyloid 40 was normal. Histological
      and quantitative real-time RT-PCR analyses showed normal gross hippocampal
      morphology and unaltered expression of three genes involved in inflammatory
      responses in PS1 KI mice. These results show hippocampal spatial memory
      impairments caused by the PS1 M146V mutation and age-related deterioration of the
      memory impairment, suggesting that PS1 KI mice are a valuable model system for
      the study of memory loss in AD.

PMID- 16908999
TI  - RNA-targeted suppression of stress-induced allostasis in primate spinal cord
      neurons.
AB  - Peripheral acetylcholine levels notably control the synthesis in macrophages of
      pro-inflammatory cytokines; however, it remains unclear whether this peripheral
      regulatory pathway affects central nervous system neurons. To explore the
      interrelationship between neuronal cholinergic homeostasis and peripheral
      inflammatory responses in primates, we used spinal cord sections from cynomolgus
      monkeys after 7 days oral or intravenous treatment with Monarsen oligonucleotide.
      Monarsen is an antisense oligonucleotide 3'-protected by 2'-oxymethylation, which
      was proved to induce selective destruction of the stress-induced
      acetylcholinesterase splice variant AChE-R mRNA. Handling stress predictably
      suppressed neuronal choline acetyl transferase (ChAT) and the vesicular
      acetylcholine transporter (VAChT) in all treated monkeys. In Monarsen-treated
      animals, we further observed suppression of stress-induced increases in plasma
      AChE activities. Corresponding decreases in AChE-R mRNA were seen in spinal cord
      neurons, associated with parallel decline patterns in the mRNA encoding for the
      splice factor SC35 (the levels of which co-increase with those of AChE-R) as well
      as in the neuronal pro-inflammatory interleukins IL-1beta and IL-6. The antisense
      effects showed direct dose dependence and were inversely associated with neuronal
      cell size. These findings suggest a causal association between neuronal
      cholinergic allostasis and inflammatory reactions in primates and support the
      peripheral use of RNA-targeted intervention with AChE-R accumulation for the
      management of both stress and inflammatory responses.

PMID- 16909000
TI  - TAU haplotype and the Saitohin Q7R gene polymorphism do not influence CSF Tau in
      Alzheimer's disease and are not associated with frontotemporal dementia or
      Parkinson's disease.
AB  - BACKGROUND: Recent studies have described Saitohin(STH), a gene located in the
      human TAU gene. The corresponding protein shows a similar tissue expression to
      tau, which is involved in many neurodegenerative disorders including Alzheimer's
      disease (AD), frontotemporal dementia (FTD) and Parkinson's disease (PD). A
      single nucleotide polymorphism in the STH gene has been suggested to be involved
      in sporadic AD and is in complete linkage disequilibrium with the TAU haplotype
      H1. OBJECTIVE: A case-control study was performed to further explore the possible
      involvement of the STH Q7R polymorphism and the extended TAU haplotype in AD, FTD
      or PD. METHODS: Patients with AD (n = 398), FTD (n = 96) and PD (n = 105), and
      controls (n = 186) were genotyped for the STH polymorphism and/or the TAU
      haplotype. Genotype data were related to levels of total-tau, phospho-tau and
      Abeta(1-42) in cerebral spinal fluid (CSF) in more than 300 AD patients and to an
      amount of senile plaques and neurofibrillary tangles in the frontal cortex and
      hippocampus in patients with autopsy-confirmed AD. RESULTS: The STH Q7R
      polymorphism and the TAU haplotype were in complete linkage disequilibrium in all
      patients (AD and FTD) and controls investigated for both genes. There were no
      significant differences in genotype or allele distributions in AD, FTD or PD
      cases compared to controls. Neither TAU haplotype nor STH influenced CSF levels
      of total-tau, phospho-tau and Abeta(1-42) significantly. In AD patients with
      neuropathological scores of plaque and tangles, no associations with TAU
      haplotype and STH were found. CONCLUSION: We found no evidence that could support
      a major pathogenic role of STH and TAU haplotype in AD, FTD or PD.

PMID- 16909001
TI  - Passive immunization of the Abeta42(43) C-terminal-specific antibody BC05 in a
      mouse model of Alzheimer's disease.
AB  - BACKGROUND: Over the past few years, amyloid beta protein (Abeta) vaccination has
      become one of the most effective treatments for Alzheimer's disease. However, the
      appearance of severe side effects during clinical trials has highlighted the need
      for improved safety and efficacy. Although antibodies directed against the amino
      (N)-termini of Abeta are highly effective for passive immunization, a substantial
      risk of inducing cerebral hemorrhage has been documented. OBJECTIVE: We
      investigated the effect of the administration of BC05, which was the first
      antibody developed against the carboxyl (C)-termini of Abeta42(43), on the
      clearance of brain Abeta42(43). METHOD: The BC05 antibody was injected into the
      peritoneal cavity of Tg2576 transgenic mice expressing betaAPP(KM670/671NL) once
      a week from 3 to 12 months of age. RESULTS: BC05 caused a selective 44-fold
      increase in plasma Abeta42(43) and a significant increase in brain soluble
      Abeta42(43), showing a 156% difference. Brain insoluble Abeta40 and Abeta42(43)
      levels were decreased by 27.3 and 31.5%, respectively. A reduction in the number
      of BAN50-labeled plaques was observed. CONCLUSIONS: BC05 might render Abeta42(43)
      soluble within the brain and inhibit the insoluble deposition of Abeta40 and
      Abeta42(43). By analyzing the mechanism of the elevation of soluble Abeta42(43)
      after passive immunization of BC05, safer and more effective methods of
      immunotherapy for Alzheimer's disease might be developed.

PMID- 16909002
TI  - MPTP treatment impairs tyrosine hydroxylase immunopositive fibers not only in the
      striatum, but also in the amygdala.
AB  - Parkinson's disease (PD) is characterized by a triad of symptoms (tremor,
      rigidity, and bradykinesia). Aside from this, emotional deficits are known to be
      associated with PD. A key structure of emotional processing is the amygdala.
      Emotional deficits seen in PD might be due to alterations in the
      catecholaminergic innervation of this limbic structure. We therefore examined
      whether 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) applied to C57/BL6
      mice (an animal model of PD) affects the density of tyrosine hydroxylase (TH)
      immunoreactive fibers in the amygdala as it does in the striatum. MPTP treatment
      caused a prominent reduction in dopamine levels (about -70%) in the striatum
      (determined by high-performance liquid chromatography and electrochemical
      detection), accompanied by massive losses of TH-positive fibers in the striatum (
      48.3%). Moreover, MPTP treatment caused prominent reductions of TH-positive fiber
      densities in the basolateral, lateral and central nucleus of the amygdala (about 
      20%). These results may provide the morphological basis for behavioral studies
      analyzing altered emotional responses in animal models of PD.

PMID- 16909003
TI  - Cholesterol 25-hydroxylase on chromosome 10q is a susceptibility gene for
      sporadic Alzheimer's disease.
AB  - Alzheimer's disease (AD) is the most common cause of dementia. It is
      characterized by beta-amyloid (A beta) plaques, neurofibrillary tangles and the
      degeneration of specifically vulnerable brain neurons. We observed high
      expression of the cholesterol 25-hydroxylase (CH25H) gene in specifically
      vulnerable brain regions of AD patients. CH25H maps to a region within 10q23 that
      has been previously linked to sporadic AD. Sequencing of the 5' region of CH25H
      revealed three common haplotypes, CH25Hchi2, CH25Hchi3 and CH25Hchi4; CSF levels
      of the cholesterol precursor lathosterol were higher in carriers of the CH25Hchi4
      haplotype. In 1,282 patients with AD and 1,312 healthy control subjects from five
      independent populations, a common variation in the vicinity of CH25H was
      significantly associated with the risk for sporadic AD (p = 0.006). Quantitative
      neuropathology of brains from elderly non-demented subjects showed brain A beta
      deposits in carriers of CH25Hchi4 and CH25Hchi3 haplotypes, whereas no A beta
      deposits were present in CH25Hchi2 carriers. Together, these results are
      compatible with a role of CH25Hchi4 as a putative susceptibility factor for
      sporadic AD; they may explain part of the linkage of chromosome 10 markers with
      sporadic AD, and they suggest the possibility that CH25H polymorphisms are
      associated with different rates of brain A beta deposition.

PMID- 16909004
TI  - Increased cerebrospinal fluid A beta38/A beta42 ratio in Alzheimer disease.
AB  - We quantitated amyloid beta peptide (A beta) 38, A beta40 and A beta42 levels in
      matched CSF and plasma from Alzheimer disease (AD) patients and controls. CSF A
      beta38 and A beta40 levels were similar in AD patients and in controls; however,
      they were higher in controls with APOE upsilon4 allele than those without. CSF A
      beta42 levels were lower in AD patients than in controls. The CSF A beta38/42
      ratio was higher in AD patients than controls, consistent with the previously
      reported higher A beta40/42 ratio. A beta38, A beta40 and A beta42 levels in
      plasma were similar in AD patients and in controls and showed no relationship to
      levels in CSF. Our findings suggest that the increased CSF A beta38/42 ratio
      found in AD patients is derived entirely from reduction of CSF A beta42 levels.

PMID- 16909005
TI  - Celastrol blocks neuronal cell death and extends life in transgenic mouse model
      of amyotrophic lateral sclerosis.
AB  - There is substantial evidence that both inflammation and oxidative damage
      contribute to the pathogenesis of motor neuron degeneration in the G93A SOD1
      transgenic mouse model of amyotrophic lateral sclerosis (ALS). Celastrol is a
      natural product from Southern China, which exerts potent anti-inflammatory and
      antioxidative effects. It also acts potently to increase expression of heat shock
      proteins including HSP70. We administered it in the diet to G93A SOD1 mice
      starting at 30 days of age. Celastrol treatment significantly improved weight
      loss, motor performance and delayed the onset of ALS. Survival of celastrol
      treated G93A mice increased by 9.4% and 13% for 2 mg/kg/day and 8 mg/kg/day
      doses, respectively. Cell counts of lumbar spinal cord neurons confirmed a
      protective effect, i.e. 30% increase in neuronal number in the lumbar spinal
      cords of celastrol-treated animals. Celastrol treatment reduced TNF-alpha, iNOS,
      CD40, and GFAP immunoreactivity in the lumbar spinal cord sections of celastrol
      treated G93A mice compared to untreated G93A mice. TNF-alpha immunoreactivity co
      localized with SMI-32 (neuronal marker) and GFAP (astrocyte marker). HSP70
      immunoreactivity was increased in lumbar spinal cord neurons of celastrol-treated
      G93A mice. Celastrol has been widely used in treating inflammatory diseases in
      man, and is well tolerated; therefore, it may be a promising therapeutic
      candidate for the treatment of human ALS.

PMID- 16909006
TI  - A beta immunotherapy: Lessons learned for potential treatment of Alzheimer's
      disease.
AB  - Amyloid-beta (A beta) immunotherapy for treatment of Alzheimer's disease (AD) was
      first described in 1999 and has been very informative regarding the role of A
      beta in AD. Through the efforts of many laboratories we now know that it is
      possible to reduce amyloid burden and many related AD pathologies in numerous
      animal models of the disease. Furthermore, initial clinical testing with AN1792,
      composed of A beta(1-42 )and an adjuvant, has yielded very important insights
      into both the clinical potential of the approach and the impact of A beta peptide
      on the disease. A brief review of our current understanding of A beta
      immunotherapy is described. These findings have led to newer alternative A beta
      immunotherapy approaches that include both active and passive approaches that are
      currently in clinical testing in both the USA and Europe.

PMID- 16909007
TI  - Mechanisms of A beta plaque clearance following passive A beta immunization.
AB  - Alzheimer's disease is a major health problem with limited available medical
      treatment options. Immunotherapy is one approach with the potential to slow or
      reverse the disease process. In transgenic mouse models of amyloid deposition,
      anti-A beta immunotherapy is remarkably effective at diminishing the amyloid
      burden and reversing the memory deficiency phenotype present in these mice. Three
      distinct mechanisms of antibody action have been proposed to mediate these
      benefits of anti-A beta immunotherapy. The first is a catalytic dissolution of
      the A beta fibrils, proposed by Beka Solomon and colleagues. A second mechanism
      is opsonization of the amyloid by the antibody and subsequent phagocytosis by
      macrophages proposed by Dale Schenk and the Elan group. A third mechanism
      proposed by DeMattos, Holtzman and colleagues is the peripheral sink hypothesis,
      arguing that circulating antibodies sequester A beta and favor efflux of A beta
      from the CNS over influx to the CNS. None of these mechanisms are mutually
      exclusive. Our research group has evaluated these mechanisms using intracranial
      injection and systemic administration of anti-A beta antibodies. We found
      evidence supporting all three mechanisms, and suggest they may act
      synergistically to achieve the large effect size of the immunotherapeutic
      approach. However, in aged amyloid precursor protein transgenic mice administered
      anti-A beta antibodies systemically, there is a redistribution of the amyloid
      from the parenchyma to vascular elements. This increase in congophilic angiopathy
      is associated with increased risk of microhemorrhage. Thus, although we favor
      continued testing of the immunotherapy to treat Alzheimer's disease, we believe
      caution should be taken to minimize the risk of vascular leakage.

PMID- 16909008
TI  - Developing novel immunogens for an effective, safe Alzheimer's disease vaccine.
AB  - Active amyloid beta (A beta) vaccination has been shown to be effective in
      clearing cerebral A beta and improving cognitive function in mouse models of
      Alzheimer's disease. However, an A beta vaccine clinical trial was suspended
      after meningoencephalitis was detected in a subset of subjects. Passive
      immunization has been suggested to be a safer alternative to active A beta
      immunization but there are reports of increased risk of microhemorrhages
      associated with its administration in aged beta-amyloid precursor protein
      transgenic mice bearing abundant vascular amyloid deposition. In addition, the
      cost may be prohibitive for large-scale clinical use. Therefore, we are designing
      novel A beta immunogens that encompass the B cell epitope of A beta but lack the
      T cell-reactive sites. These immunogens induced the production of A beta-specific
      antibodies in the absence of an A beta-specific cellular immune response in wild
      type mice and are being tested in beta-amyloid precursor protein transgenic mice.
      These data together with published reports from several other groups suggest that
      a safe, active A beta vaccine is a tenable goal.

PMID- 16909009
TI  - Clinical observations with AN-1792 using TAPIR analyses.
AB  - Clinical observations with AN-1792 using tissue amyloid plaque immunoreactivity
      (TAPIR) analyses established for the first time evidence in humans that
      antibodies against beta-amyloid-related epitopes are capable of slowing
      progression in Alzheimer's disease. Antibodies derived upon TAPIR assay selection
      may specifically target the pathologic neoepitopes of aggregated A beta species
      present in amyloid plaques and some of their aggregated, protofibrillar and low
      molecular weight oligomeric precursors. We briefly summarize here how the proof
      of concept was established and why it provides the basis for a potential cure for
      Alzheimer's disease.

PMID- 16909010
TI  - APP processing and the APP-KPI domain involvement in the amyloid cascade.
AB  - Alternative APP mRNA splicing can generate isoforms of APP containing a Kunitz
      protease inhibitor (KPI) domain. KPI is one of the main serine protease
      inhibitors. Protein and mRNA KPI(+)APP levels are elevated in Alzheimer's disease
      (AD) brain and are associated with increased amyloid beta deposition. In the last
      years increasing evidence on multiple points in the amyloid cascade where
      KPI(+)APP is involved has been accumulated, admitting an outstanding position in
      the pathogenesis of AD to the KPI domain. This review focuses on the APP
      processing, the molecular activity of KPI and its physiological and pathological
      roles and the KPI involvement in the amyloid cascade through the nerve growth
      factor, the lipoprotein receptor-related protein, the tumor necrosis factor-alpha
      converting enzyme and the Notch1 protein.

PMID- 16909011
TI  - BACE/APPV717F double-transgenic mice develop cerebral amyloidosis and
      inflammation.
AB  - Most of the transgenic mice generated to model Alzheimer's disease express human
      amyloid precursor protein (APP) mutants alone or in conjunction with presenilin
      mutants. We have generated a mouse model by overexpressing human BACE and human
      APP with the V717F mutation. The combination of a mutation at the gamma-secretase
      cleavage site of APP and of increased beta-secretase activity should favour the
      production of amyloid peptides. We analysed double BACE/APPIn and single APPIn
      transgenic mice at 16-18 months for amyloid load, brain histopathology and
      behavioural deficits. We show that overexpression of BACE induces an increase in
      APP CTFbeta and total brain Abeta peptides. Brain histopathology shows clearly
      enhanced amyloid deposits in the cortex, hippocampus and in brain vasculature
      when compared to single APPIn transgenic mice. Amyloid deposits are mostly
      diffuse and predominantly composed of Abeta(42). A strong inflammatory reaction
      is evidenced by the presence of microglial cells around the most mature amyloid
      deposits and astrocytosis over the entire cerebral cortex. At the same age, the
      APPIn single-transgenic mice show only very limited pathology. When assessed for
      their cognitive performance at 12 months, BACE/APPIn mice show impaired spatial
      acquisition in the Morris water maze test. However, these deficits are not
      greater than those observed in the APPIn single-transgenic animals.

PMID- 16909012
TI  - Plasma homocysteine and risk of coexisting silent brain infarction in Alzheimer's
      disease.
AB  - BACKGROUND: Cerebrovascular disease is common in Alzheimer's disease (AD).
      Elevated plasma homocysteine (pHcy) levels are reported to be associated with an
      increased risk of poor cognition and dementia. OBJECTIVE: To determine whether
      high pHcy levels are associated with an increased risk of coexisting silent brain
      infarctions (SBIs) in AD. METHODS: Study population comprising 143 outpatients
      with clinical diagnosis of probable AD (73.3 +/- 7.0 years) were classified into
      2 groups according to the presence or absence of SBIs on magnetic resonance
      imaging. RESULTS: SBIs were noted in 32.9% (47/143) of the AD patients. The pHcy
      levels in the AD with SBIs (14.0 +/- 4.5 micromol/l) were significant ly elevated
      compared with the AD without SBIs (11.7 +/- 4.7 micromol/l, p = 0.007). After
      adjusting for age and gender, high pHcy (>12.4 micromol/l), but not hypertension,
      was associated with an increased risk of developing SBIs in AD (OR = 4.61, 95% CI
      = 1.74-12.2, p = 0.002). However, age at onset, cognitive function, cerebrospinal
      tau or amyloid beta-peptide(1-42) levels were not significantly correlated with
      pHcy levels in AD. CONCLUSION: SBIs commonly coexist with AD, and may be a unique
      vascular condition in which homocysteine plays an important role. Homocysteine
      lowering therapy rather than antihypertensive medication might be an appropriate
      strategy to prevent stroke associated with AD.

PMID- 16909014
TI  - Modeling neurodegenerative diseases in vivo review.
AB  - Parkinson's disease (PD) is one of the major neurodegenerative disorders. The
      etiology of this disease is likely due to combinations of environmental and
      genetic factors. Symptomatic hallmarks of PD are tremor, bradykinesia, rigidity
      and postural instability. On the morphological and anatomical level, PD is
      characterized by massive degeneration of dopaminergic neurons in the substantia
      nigra pars compacta, leading to a severe loss of striatal dopaminergic fibers and
      to a massive reduction of dopamine levels in the striatum. In addition, PD is
      characterized by the appearance of Lewy bodies within the surviving dopaminergic
      neurons. Animal models of PD allow getting insight into the mechanisms of several
      symptoms of PD thereby providing indispensable tools for basic and applied
      research. The biochemical and cellular changes that occur following
      administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in rodents
      or monkeys are remarkably similar to those seen in idiopathic PD. In this review,
      the main characteristics of experimental models of PD induced by the neurotoxic
      compound MPTP are reviewed.

PMID- 16909013
TI  - Prevalence and effects of lobar microhemorrhages in early-stage dementia.
AB  - BACKGROUND: 80-100% of patients with Alzheimer's disease have vascular pathology
      related to cerebral amyloid angiopathy (CAA), and 5-7% have CAA-related lobar
      microhemorrhages (LMH) at autopsy. The prevalence and effects of LMH detectable
      by gradient echo MRI (GE-MRI) in early-stage dementia are unknown. OBJECTIVE: To
      obtain, using GE-MRI, a prevalence estimate for LMH in patients with early-stage
      dementia and to assess the effects of LMH on dementia severity. METHODS: Eighty
      four subjects aged >or=55 years (range 58-89; mean 76) underwent cognitive and GE
      MRI evaluation. The 84 subjects consisted of 61 consecutive subjects evaluated as
      part of an initial clinical evaluation for dementia and 23 consecutively
      evaluated healthy older subjects (controls). Data were analyzed for presence and
      number of LMH on GE-MRI and the effect of number of LMH on dementia severity.
      RESULTS: Nine (15%) of the 61 dementia patients versus 1 (4%) of the 23 control
      subjects demonstrated LMH on GE-MRI. Multiple (>or=2) LMH were found in 7 of the
      9 (88%) dementia subjects with LMH (range of LMH counts 1-330) and no (0%)
      control subjects. Multivariable causal modeling indicated that number of LMH (p <
      0.02), age (p < 0.01) and duration of symptoms (p < 0.001) significantly
      increased dementia severity while higher educational level (p < 0.001) was
      protective. CONCLUSIONS: LMH were detected by GE-MRI in 15% of patients with
      early-stage dementia and may contribute to dementia severity.

PMID- 16909016
TI  - Mutant SOD1 instability: implications for toxicity in amyotrophic lateral
      sclerosis.
AB  - The biological basis of preferential motor neuron degeneration in amyotrophic
      lateral sclerosis (ALS) remains incompletely understood, and effective therapies
      to prevent the lethal consequences of this disorder are not yet available. Since
      1993, more than 100 mutant variants of the antioxidant enzyme Cu/Zn superoxide
      dismutase (SOD1) have been identified in familial ALS. Many studies have sought
      to distinguish abnormal properties shared by these proteins that may contribute
      to their toxic effects and cause age-dependent motor neuron loss. Complex
      networks of cellular interactions and changes associated with aging may link
      mutant SOD1s and other stresses to motor neuron death in ALS. Our laboratory and
      collaborators have compared physicochemical properties of biologically metallated
      wild-type and mutant SOD1 proteins to discern specific vulnerabilities that may
      be relevant to the mutant toxicity in vivo. X-ray crystal structures obtained
      from metallated 'wild-type-like' (WTL) SOD1 mutants, which retain the ability to
      bind copper and zinc and exhibit normal specific activity, indicate a native-like
      structure with only subtle changes to the backbone fold. In contrast, a group of
      'metal-binding region' (MBR) SOD1 mutants that are deficient in copper and zinc
      exhibit severe thermal destabilization and structural disorder of conserved loops
      near the metal-binding sites. A growing body of evidence highlights specific
      stresses in vivo that may perturb well-folded, metallated SOD1 variants and
      thereby favor an increased burden of partially unfolded, metal-deficient species.
      For example, WTL SOD1 mutants are more susceptible than wild-type SOD1 to
      reduction of the intrasubunit disulfide bond between Cys-57 and Cys-146 at
      physiological pH and temperature. This bond anchors the disulfide loop to the
      SOD1 beta-barrel and helps to maintain the dimeric configuration of the protein.
      Cleavage of the disulfide linkage renders the well-folded WTL mutants vulnerable
      to metal loss and monomerization such that they may resemble the destabilized and
      locally misfolded MBR mutant species. SOD1 proteins with disordered loops or
      monomeric structure are expected to be more susceptible to aberrant self
      association or detrimental interactions with other cellular constituents. The
      challenge for future investigations is to relate these abnormal properties of
      partially unfolded SOD1 to specific mechanisms of toxicity in motor neurons,
      supporting cells, or target tissues.

PMID- 16909017
TI  - Inter- and intracellular signaling in amyotrophic lateral sclerosis: role of p38
      mitogen-activated protein kinase.
AB  - The pathogenetic processes underlying the selective motor neuron degeneration in
      amyotrophic lateral sclerosis (ALS) are complex and still not completely
      understood even in the cases of inherited disease caused by mutations in the
      Cu/Zn superoxide dismutase-dependent (SOD1) gene. Recent evidence supports the
      view that ALS is not a cell-autonomous disease and that glial-neuron cross-talk,
      throughout cytokines and other toxic factors like the nitric oxide and
      superoxide, is a crucial determinant for the induction of motor neuron death.
      This cell-cell interaction may determine the progression of the disease through
      processes that are likely independent of the initial trigger and that may
      converge on the activation of intracellular death pathways in the motor neurons.
      In this review we provide support to the hypothesis that aberrant expression and
      activity of p38 mitogen protein-activated kinases cascade (p38MAPK) in motor
      neurons and glial cells may play a role in the development and progression of
      ALS. Increased activation of p38MAPK may phosphorylate neuron-specific substrates
      altering their physiological properties and it may turn on responsive genes
      leading to neurotoxicity.

PMID- 16909018
TI  - Anti-ALS activity of alsin, the product of the ALS2 gene, and activity-dependent
      neurotrophic factor.
AB  - Amyotrophic lateral sclerosis (ALS) is an incurable degenerative motoneuronal
      disease. The complete suppression of motoneuronal death is the ultimate goal of
      ALS therapy. Two new prosurvival pathways have been recently demonstrated to
      antagonize neurotoxicity by familial ALS-linked mutant Cu/Zn-superoxide dismutase
      (FSOD1). Alsin, the product of the recently cloned ALS-causative gene, the ALS2
      gene, is linked to a Rac1/phosphatidylinositol-3 kinase/Akt3 pathway that
      specifically suppresses motoneuronal death induced by FSOD1. Activity-dependent
      neurotrophic factor, originally identified as an anti-Alzheimer neurotrophic
      factor, has been shown to suppress motoneuronal death by FSOD1 through a
      prosurvival pathway mediated by Ca(2+)/calmodulin-dependent protein kinase IV.
      Activation of these novel anti-ALS pathways may serve as a promising way to
      suppress ALS-related motoneuronal cell death.

PMID- 16909019
TI  - Complexity of astrocyte-motor neuron interactions in amyotrophic lateral
      sclerosis.
AB  - Neurons and surrounding glial cells compose a highly specialized functional unit.
      In amyotrophic lateral sclerosis (ALS) astrocytes interact with motor neurons in
      a complex manner to modulate neuronal survival. Experiments using chimeric mice
      expressing ALS-linked mutations to Cu,Zn superoxide dismutase (SOD-1) suggest a
      critical modulation exerted by neighboring non-neuronal cell types on disease
      phenotype. When perturbed by primary neuronal damage, e.g. expression of SOD-1
      mutations, neurons can signal astrocytes to proliferate and become reactive.
      Fibroblast growth factor-1 (FGF-1) can be released by motor neurons in response
      to damage to induce astrocyte activation by signaling through the receptor FGFR1.
      FGF-1 stimulates nerve growth factor (NGF) expression and secretion, as well as
      activity of the nuclear factor erythroid 2-related factor 2 (Nrf2) transcription
      factor. Nrf2 leads to the expression of antioxidant and cytoprotective enzymes
      such as heme oxygenase-1 and a group of enzymes involved in glutathione
      metabolism that prevent motor neuron degeneration. However, prolonged stimulation
      with FGF-1 or SOD-mediated oxidative stress in astrocytes may disrupt the normal
      neuron-glia interactions and lead to progressive neuronal degeneration. The re
      expression of p75 neurotrophin receptor and neuronal NOS in motor neurons in
      parallel with increased NGF secretion by reactive astrocytes may be a mechanism
      to eliminate critically damaged neurons. Consequently, astrocyte activation in
      ALS may have a complex pathogenic role.

PMID- 16909020
TI  - Excitotoxicity and amyotrophic lateral sclerosis.
AB  - Since its description by Charcot more than 130 years ago, the pathogenesis of
      selective motor neuron degeneration in amyotrophic lateral sclerosis (ALS)
      remains unsolved. Over the years, many pathogenic mechanisms have been proposed.
      Amongst others these include: oxidative stress, excitotoxicity, aggregate
      formation, inflammation, growth factor deficiency and neurofilament
      disorganization. This multitude of contributing factors indicates that ALS is a
      complex disease and also suggests that ALS is a multifactorial disorder.
      Excitotoxicity is not the newest and most spectacular hypothesis in the ALS
      field, but it is undoubtedly one of the most robust pathogenic mechanisms
      supported by an impressive amount of evidence. Moreover, the therapeutic efficacy
      of riluzole, the only drug proven to slow disease progression in ALS, is most
      likely related to its anti-excitotoxic properties. In this review, we will give
      an overview of the arguments in favor of the involvement of excitotoxicity in ALS
      and of the possible mechanisms leading to motor neuron death. We will also
      summarize the intrinsic properties of motor neurons that render these cells
      particularly vulnerable to excitotoxicity and could explain the selective
      vulnerability of motor neurons in ALS. All this information could help to develop
      new and better therapeutic strategies that could protect motor neurons from
      excitotoxicity.

PMID- 16909021
TI  - Enprofylline protects motor neurons from in vitro excitotoxic challenge.
AB  - BACKGROUND: The death of motor neurons in amyotrophic lateral sclerosis (ALS) is
      believed to result, in part, from unrestrained activation of glutamate receptors
      (excitotoxicity). In some in vitro models, excitotoxic death only occurs if motor
      neurons develop in the presence of the growth factor, brain-derived neurotrophic
      factor (BDNF). OBJECTIVE: Since the increased vulnerability of motor neurons
      evoked by BDNF is mediated by activation of TrkB, we sought to identify
      pharmacological agents that can block this pathway. Adenosine receptors are known
      to transactivate Trk receptors, leading us to examine the effects of manipulating
      of adenosine receptor signaling on Trk signaling and excitotoxic sensitivity.
      METHODS: Spinal cord cultures were treated with adenosine receptor agonists and
      antagonists. The biochemical effects on Trk signaling and excitotoxic motor
      neuron death were examined. RESULTS: We show here that adenosine A(2a)
      antagonists can reduce activation of Trk receptors and are neuroprotective.
      Conversely, activating adenosine A(2a) receptors in the absence of BDNF signaling
      makes motor neurons vulnerable to excitotoxic challenge. CONCLUSION: Selective,
      high-affinity adenosine A(2a) antagonists merit consideration as therapeutic
      agents for the treatment of ALS.

PMID- 16909022
TI  - Implications for the kynurenine pathway and quinolinic acid in amyotrophic
      lateral sclerosis.
AB  - The kynurenine pathway (KP) is a major route of L-tryptophan catabolism leading
      to production of several neurobiologically active molecules. Among them is the
      excitotoxin quinolinic acid (QUIN) that is known to be involved in the
      pathogenesis of several major inflammatory neurological diseases. In amyotrophic
      lateral sclerosis (ALS) degeneration of motor neurons is associated with a
      chronic and local inflammation (presence of activated microglia and astrocytes).
      There is emerging evidence that the KP is important in ALS. Recently, we
      demonstrated that QUIN is significantly increased in serum and CSF of ALS
      patients. Moreover, most of the factors associated with QUIN toxicity are found
      in ALS, implying that QUIN may play a substantial role in the neuropathogenesis
      of ALS. This review details the potential role the KP has in ALS and advances a
      testable hypothetical model.

PMID- 16909023
TI  - Amyotrophic lateral sclerosis: new developments in diagnostic markers.
AB  - There is an intensive search for diagnostic markers in amyotrophic lateral
      sclerosis (ALS). Protein analysis (proteomics) of the cerebrospinal fluid (CSF)
      appears particularly promising using mass spectrometry and 2-D gel
      electrophoresis to detect low and high molecular weight proteins, respectively.
      It is open whether protein changes specific for ALS will be found. This also
      holds true for inflammatory proteins such as the cytokine monocyte
      chemoattractant protein-1 which has been detected in CSF in ALS and for other
      cytokines such as interleukin-1beta. Increases of the protein Nogo A and B in
      muscle tissue and decreases of the growth factor vascular endothelial growth
      factor in blood may also be useful for monitoring the course of ALS. Clinical
      neurophysiology provides markers for upper and lower motor neuron damage. A very
      sensitive method to detect early upper motor neuron involvement is the
      transcranial magnetic stimulation modification 'triple stimulation technique'
      which can show significant changes in patients without clinical upper motor
      neuron signs. The loss of lower motor neurons can be closely monitored by MUNE
      techniques (motor unit number estimate). In modern imaging, the MRI technique DTI
      (diffusion tensor imaging) has the greatest diagnostic potential for ALS. It can
      separate between normal and ALS in group comparisons and may be improved to be
      diagnostic in individual patients. Voxel-based morphometry can reliably
      demonstrate regional cortical atrophy in motor areas and beyond although it is
      not appropriate for use in individual patients.

PMID- 16909024
TI  - Reticulons as markers of neurological diseases: focus on amyotrophic lateral
      sclerosis.
AB  - Reticulons (RTNs) are a family of proteins that are primarily associated with the
      endoplasmic reticulum. In mammals, four genes have been identified and referred
      as to rtn1, 2, 3 and the neurite outgrowth inhibitor rtn4/nogo. These genes
      generate multiple isoforms that contain a common C-terminal reticulon homology
      domain of 150-200 amino-acid residues. The N-terminal regions of RTNs are highly
      variable, and result from alternative splicing or differential promoter usage.
      Although widely distributed, the functions of RTNs are still poorly understood.
      Much interest has been focused on rtn4/nogo because of its activity as a potent
      inhibitor of axonal growth and repair. In the present study, we update recent
      knowledge on mammalian RTNs paying special attention to the involvement of these
      proteins as markers of neurological diseases. We also present recent data
      concerning RTN expression in amyotrophic lateral sclerosis, a fatal degenerative
      disorder characterized by loss of upper and lower motor neurons, and muscle
      atrophy. The rearrangement of RTN expression is regulated not only in suffering
      skeletal muscle but also preceding the onset of symptoms, and may relate to the
      disease process.

PMID- 16909025
TI  - Lead exposure as a risk factor for amyotrophic lateral sclerosis.
AB  - BACKGROUND: The etiology of amyotrophic lateral sclerosis (ALS) likely involves
      an environmental component. We qualitatively assessed literature on ALS and lead
      exposure. Problems of study design make case reports and studies of lead in blood
      or tissues difficult to interpret. Most previous case-control studies found an
      association of ALS with self-reported occupational exposure to lead, with
      increased risks of 2- to >4-fold. However, these results may have been affected
      by recall bias. OBJECTIVE: To address inconsistencies among published reports, we
      used both lead biomarkers and interview data to assess lead exposure, and we
      evaluated the role of genetic susceptibility to lead. METHODS: We conducted a
      case-control study in New England in 1993-1996 with 109 ALS cases and 256
      population-based controls. We measured blood and bone lead levels, the latter
      using X-ray fluorescence, and interviewed participants regarding sources of lead
      exposure. RESULTS: In our study, ALS was associated with self-reported
      occupational lead exposure, with a dose response for cumulative days of exposure.
      ALS was also associated with blood and bone lead levels, with a 1.9-fold increase
      in risk for each mug/dl increment in blood lead and a 2.3- to 3.6-fold increase
      for each doubling of bone lead. A polymorphism in the delta-aminolevulinic acid
      dehydratase gene was associated with a 1.9-fold increase in ALS risk. CONCLUSION:
      These results, together with previous studies, suggest that lead exposure plays a
      role in the etiology of ALS. An increase in mobilization of lead from bone into
      blood may play a role in the acute onset of disease.

PMID- 16909026
TI  - Hypermetabolism in ALS: correlations with clinical and paraclinical parameters.
AB  - Despite a reduction in fat-free mass (FFM), a hypermetabolism has been reported
      with an average of 10% in amyotrophic lateral sclerosis (ALS) patients as
      compared with a healthy population. The objectives of this study were to confirm
      the level of hypermetabolism determined by using indirect calorimetry in 168
      patients with a probable or a definite ALS and to study correlations with
      survival. Consecutive evaluations of resting energy expenditure (REE) were
      performed from diagnosis to the proximity of death in 44 ALS patients.
      Differences with the calculated value determined a DeltaREE. FFM was given by
      bioimpedance. At T(1), REE was significantly increased by an average of 14% as
      compared with the calculated value. 62.3% of ALS patients were considered as
      hypermetabolic. REE was correlated in univariate analysis with age, sex, clinical
      form at onset, presence of a denutrition, weight, FFM, phase angle and ALS
      Functional Rating Scale (ALSFRS). In multivariate analysis, REE was linked to age
      and FFM. DeltaREE was correlated in univariate analysis with sex, phase angle and
      manual muscle testing (MMT). In multivariate analysis, age and sex remained
      significantly correlated. During progression of ALS, REE levels remained higher
      than calculated values with a trend to decrease at proximity of death, whereas
      FFM remained stable. From T(1), survival was linked to MMT, ALSFRS, vital
      capacity, REE and phase angle. We confirmed the existence of a stable
      hypermetabolic state in ALS which depends mainly on age, sex and FFM. REE is a
      prognostic factor for survival in univariate analysis.

PMID- 16909027
TI  - Clinical trials in ALS: what did we learn from recent trials in humans?
AB  - Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease.
      No treatment is currently able to stop the disease process. In the absence of new
      active compounds there is an urgent need to develop new strategies based on the
      neuroprotective activity of available drugs. ALS is a heterogeneous disease. To
      build up these therapeutic trials, we need to have a better understanding of the
      prognostic factors in this disease. During the Phase IV Rilutek Trial in France,
      we developed in a large population of patients a prognostic score based on
      clinical parameters available at the bedside. The most significant variables are
      vital capacity, spasticity, fasciculations, swallowing, cough and creatininemia.
      This score proved to be very useful in daily use in the clinic and for planning
      disease management in ALS as in the design of therapeutic trials. In ALS clinical
      trials, efficacy can be evaluated using survival or functional parameters. In
      phase II trials, function remains the most commonly used. In phase III trials,
      the gold standard endpoint remains the survival rate at month 18. We analyzed the
      most recent ALS trials published in the literature. This review suggests that in
      these trials there is a discrepancy between drug effects on survival versus
      function. These results suggest that a reappraisal of strategies to identify
      therapeutic targets for ALS is required.

PMID- 16909028
TI  - Preclinical trials--an update on translational research in ALS.
AB  - Translational research has become a strategy which describes the steps from in
      vitro experimental therapy, its translation into experimental animals and finally
      to humans. However, this translation of hypotheses from one of these levels to
      another faces a number of difficulties which are currently of major interest for
      the development of therapeutics. In particular, in the previously untreatable
      motor neuron diseases, the steps from genes to transgenic animals and finally to
      the patient have proven difficult. High expectations have not met with the
      transfer of numerous therapies from experimental animals to men; there are many
      in- and outside the field which already question the value of animal models. It
      is the opinion of the authors that we should not dismiss the models before we
      have not defined generally accepted standards of protocols for therapeutic
      studies in experimental animals. Only if a generally agreed standardized and
      validated methodology in mice cannot predict the human response to therapeutics,
      an animal model should be abandoned. In contrast, the value of translating
      genetic findings to experimental animals and men is currently shown for motor
      proteins; in particular the functional impact of dynactin and dynein for the
      integrity of motor neurons of rodents and men are in the center of interest.

PMID- 16909029
TI  - Promises and challenges in developing RNAi as a research tool and therapy for
      neurodegenerative diseases.
AB  - RNA interference (RNAi) is a recently discovered mechanism that is conserved in a
      wide range of eukaryotic species. Triggered by double-stranded RNA, RNAi
      identifies and destroys the mRNA that shares homology with the double-stranded
      RNA. Because of its specificity, RNAi has a high potential for being a powerful
      investigative and therapeutic tool. Indeed, its use as a reverse genetics tool to
      determine gene functions in invertebrates and cultured mammalian cells has
      already been experiencing an explosive growth. Gratifyingly we have also seen its
      application in dissecting neurodegeneration pathways in vitro. Although early
      studies suggested that RNAi could be readily adapted for in vivo studies in
      mammals using the transgenic technology, difficulties including low transgenicity
      and low RNAi efficacy have emerged, which has prevented the wide use of
      transgenic RNAi. The potential of RNAi therapy for human diseases has been a
      great source of excitement. Several new studies have demonstrated this concept in
      animal models of neurodegenerative disease. In this review, we highlight the
      recent literature and our own data in applying RNAi in research and therapy in
      the area of neurodegenerative diseases. We discuss the present and future
      challenges in the full realization of the potential for RNAi.

PMID- 16909030
TI  - Function of Wnts in dopaminergic neuron development.
AB  - Dopaminergic (DA) neurons in the ventral midbrain (VM) are one of the major cell
      types lost in Parkinson's disease (PD). Proof of principle exists for cell
      replacement therapies for PD, but wider application is halted by the
      unavailability of abundant sources of DA neurons. Stem cells might constitute one
      of these sources. However, efficient protocols promoting their specific
      differentiation into a DA neuronal phenotype are required. In this review, we
      summarize the latest findings concerning the contribution of the Wnt family of
      glycolipoproteins in the development of VM DA neurons. Regulators of Wnt
      signaling are involved in several neurodevelopmental processes. Recent results
      indicate that Wnts are key regulators of proliferation and differentiation of DA
      precursors during VM neurogenesis and different Wnts have specific and unique
      activity profiles. Interestingly, chemical inhibitors of glycogen synthase kinase
      3beta stabilize beta-catenin and increase DA differentiation in VM precursor
      cultures. We hereby propose that Wnts are likely to contribute in the future to
      improve stem/precursor cell replacement therapy approaches to PD.

PMID- 16909031
TI  - Proliferation and differentiation of adult endogenous neural stem cells in
      response to neurodegenerative process within the striatum.
AB  - The ongoing process of neurogenesis in the adult mammalian forebrain suggests the
      possible capacity for limited self-repair after brain injury. Previously, we have
      demonstrated that in an animal model of Huntington's disease the
      neurodegenerative process initiates immediate intensive cell proliferation and
      differentiation resulting in characteristic enlargement of the subependymal zone
      (SEZ) of lateral brain ventricles. Now, our interest is focused on the
      architecture of the neurogenic niche of the SEZ in the identical model,
      particularly on characteristic features of astrocyte-like cells which are
      considered to be not only niche cells but also neural stem cells. Our findings
      prove higher activation of the lateral part of the SEZ (L-SEZ) adjacent to the
      degenerated striatum compared with the rostral part of the SEZ (R-SEZ). In the
      activated L-SEZ, niche cells which ensheathe clusters of neural progenitors are
      of immature astrocytic phenotype because of nestin and vimentin expression
      (except the expression of glial fibrillary acidic protein). However, the
      coexpression of all three filaments is not always found. Intermediate filaments
      also enable us to distinguish the basic shape of astrocytic cells within the SEZ,
      majority of which resemble protoplasmic rather than fibrillary astrocytes.
      Furthermore, our results show a wide plasticity of these astrocyte-like cells in
      immediate response to an extensive pathological process in the brain. These
      observations are consistent with the fact that adult stem cells undergo different
      processes in an already mature environment, and therefore can exhibit some
      specific characteristics unlike the embryonic or fetal neural stem cells.

PMID- 16909032
TI  - Neuronal differentiation of human umbilical cord blood neural stem-like cell
      line.
AB  - The expanding population of neural stem/progenitor cells can be selected from
      human cord blood nonhematopoietic (CD34-negative) mononuclear fraction. Due to
      repeated expansion and selection of these cells we have established the first
      clonogenic, nonimmortalized human umbilical cord blood neural stem-like cell
      (HUCB-NSC) line. This line can be maintained at different stages of neural
      progenitor development by the presence of trophic factors, mitogens and
      neuromorphogens in culture media. Neurogenic potential of HUCB-NSC was
      established for serum-free and low-serum cultured cells. Commitment of HUCB-NSC
      by serum was shown to be important for the optimal response to the signals
      provided by surrounding environment in vitro. Enhanced neuronal differentiation
      induced by dBcAMP treatment was accompanied by expression of several functional
      proteins including glutamatergic, GABAergic, dopamine, serotonin and
      acetylcholine receptors, which was shown by microarray, immunocytochemistry and
      electrophysiology. Electrophysiological studies, whole-cell patch-clamp
      recordings, revealed in differentiated HUCB-NSC two types of voltage-sensitive
      and several ligand-gated currents typical for neuronal cells. The above HUCB-NSC
      characteristic conceivably implicates that cord blood-derived progenitors could
      be effectively differentiated into functional neuron-like cells in vitro.

PMID- 16909033
TI  - Ih is maturing: implications for neuronal development.
AB  - Vast electrophysiological activity near resting potential, including rhythmic
      oscillatory activity, is a hallmark of many brain regions and a motor of the
      developing CNS. This activity is mediated and influenced by diverse receptor
      operated and voltage-gated ion channels. In turn, these channels are modulated
      during the course of development by altering their density, distribution and
      properties. The hyperpolarization-activated and cyclic nucleotide-gated cation
      current, Ih, impacts on the resting membrane potential and is involved in the
      generation and modulation of neuronal oscillatory activity. Therefore, it is
      conceivable that Ih is well suited to govern the specific processes involved in
      activity-dependent neuronal development. Here, we review the evidence that
      maturation of Ih accounts, at least in part, for the control of membrane
      properties during neuronal development of various parts of the brain. The
      temporal and regional variations in Ih development might underlie the normal
      maturation of neuronal circuits and, consequently, the perturbations of this
      might account for some of the neuropathology of the brain. This review summarizes
      the evidence for the stage and localization dependence of Ih in CNS development
      with a focus on arborized cells with high dendritic Ih. Further, it outlines
      hypotheses on the contribution of Ih to neuronal and network maturation.

PMID- 16909034
TI  - Toti-/pluripotential stem cells and epigenetic modifications.
AB  - Nuclear reprogramming induces global changes of epigenetic profile and confers
      pluripotency on specialized somatic nuclei. Embryonic stem (ES) cells retain
      nuclear reprogramming activity as shown by cell fusion with adult somatic cells.
      The reprogrammed somatic nuclei resemble ES cell nuclei in pluripotential
      competence. Changes of histone tail modifications in somatic cell-derived genome
      by cell fusion demonstrate that the molecular process of nuclear reprogramming is
      separable at least in two steps: erasure of somatic epigenetic modification
      (genome-wide reprogramming) and establishment of pluripotential epigenetic
      modification (gene-specific reprogramming). In the latter step, the newly
      identified transcriptional factor Nanog functions in maintaining pluripotency in
      cooperation with other key gene Oct4. Somatic-derived Nanog is reactivated in the
      reprogrammed nuclei in hybrid cells and also in cloned blastocysts. It is unclear
      which key molecules are responsible for the nuclear reprogramming. It is,
      however, evident that adult somatic cell nuclei are capable of being reprogrammed
      in vitro by cell fusion with ES cells. A technological innovation for eliminating
      ES-derived chromosomes from the hybrid nuclei could make the production of
      personalized pluripotential stem cells without the need for therapeutic cloning
      possible.

PMID- 16909035
TI  - The developing human spinal cord contains distinct populations of neural
      precursors.
AB  - It is becoming apparent that neural stem cells display some differences in their
      behaviour depending on the region of the CNS they originate from and on whether
      they are derived from embryonic or adult tissue. Whereas much work has focused on
      brain neural stem cells, less attention has been paid to spinal cord neural
      precursors, particularly in the developing human embryo. We briefly review here
      some of our work which points at some similarities between neural precursors in
      developing human spinal cords and in animals which can regenerate their spinal
      cord (e.g. tailed amphibians), and at differences in the properties of human
      neural precursors with spinal cord development. Altogether these studies suggest
      the existence of dynamic neural stem cell populations within the developing
      spinal cord. They also support the notion that thorough characterization of
      neural stem cells under different culture conditions and analysis of how these
      may affect their differentiation in vivo after grafting into different injury
      models is imperative if we are to develop effective cell therapy strategies for
      spinal cord injury and diseases.

PMID- 16909036
TI  - Developmental perspectives on human midbrain-derived neural stem cells.
AB  - Regeneration or restoration of lost or damaged neurons is very likely to
      profoundly alter the disability and needs of many patients. The replacement of
      dopaminergic (DA) neurons in patients with Parkinson's disease via implantation
      of embryonic midbrain tissue was taken from animal experiments to clinical
      applications. Ethical concerns related to the use of fetal tissue derived from
      abortions further argue for the search for alternative tissue sources. Today, it
      seems possible to generate functional DA neurons from a variety of stem cells,
      including embryonic and neural stem cells. Bone marrow stromal cells are another
      source for cell replacement. Neural stem cells derived from human fetal midbrain
      tissue maintain a considerable capacity to self-renew and to differentiate into
      DA neurons. Therefore, these cells may be a promising source to generate
      functional human DA neurons.

PMID- 16909037
TI  - Mitogen-activated protein kinase signaling, oxygen sensors and hypoxic induction
      of neurogenesis.
AB  - In the adult nervous system, neuronal subpopulations sustain a hierarchical
      pattern of selective vulnerability to hypoxia. Hypoxia also activates quiescent
      neural progenitor cells (NPCs) resulting in their amplification and subsequent
      differentiation into neurons and glia. Use of rat organotypic hippocampal
      cultures facilitates examination of early signaling events in response to hypoxia
      and reoxygenation that result in neurogenesis. Cultures were exposed to hypoxia
      for up to 6 h followed by reoxygenation. CA1 neurons showed focal nuclear
      condensation by 2 h of hypoxia, but CA2 and CA3 neurons were spared. JNKs and c
      Jun reached peak activation by 4 h, returning to basal levels by 6 h. Expression
      of oxygen sensors, hemoxygenase 2 and HIF1, were elevated by 30 min and 2 h,
      respectively. By 24 h of reoxygenation, there was proliferation of nestin
      positive NPCs. With U0126, an upstream inhibitor of ERK activation, BrdU labeling
      was markedly reduced immunohistochemically as well as PCNA protein expression,
      suggesting a role for ERKs in the proliferation response. Immunohistochemically,
      antinestin detected NPCs and on Western blots reached peak levels by 24-48 h of
      reoxygenation. Proliferation and differentiation of endogenous NPCs in the area
      of neuronal loss further suggests that mechanisms potentially exist in vitro for
      replacement with functional neurons.

PMID- 16909038
TI  - Nidogen and nidogen-associated basement membrane proteins and neuronal
      plasticity.
AB  - Extracellular matrix (ECM) proteins are thought to subserve structural functions
      as, for example, tissue barriers as well as guidance structures during cell
      growth, differentiation and tissue repair. Deletion of basement membrane (BM)
      components results in malformations of different organs, including the brain.
      Recent data, however, suggest that interference with cellular membrane-associated
      proteins interacting with ECM can alter neuronal excitability and synaptic
      plasticity without obvious underlying structural damage. This does not only apply
      to classical ECM proteins such as laminin, reelin and tenascin, but also to
      molecules of a rather specialized ECM, the BM. Here, nidogen (also termed
      entactin) appears to subserve a function in neuronal plasticity. Nidogen ablation
      leads to epileptic activity in vivo and the appearance of spontaneous
      epileptiform activity in vitro. This raises the intriguing question whether the
      BM protein nidogen may directly influence neuronal function in the CNS, opening
      the possibility of modulatory mechanisms of synaptic plasticity and excitability
      reaching beyond classical processes confined to cellular interactions.

PMID- 16909039
TI  - Magnetic resonance tracking of transplanted stem cells in rat brain and spinal
      cord.
AB  - BACKGROUND: Magnetic resonance imaging provides a noninvasive method to study the
      fate of transplanted cells in vivo. OBJECTIVE: We studied the fate of embryonic
      and mesenchymal stem cells labeled with iron oxide nanoparticles (Endorem) and
      human CD34+ cells labeled with magnetic MicroBeads (Miltenyi) in rats with a
      cortical or spinal cord lesion. METHODS: Cells were grafted intracerebrally,
      contralaterally to a cortical photochemical lesion, or injected intravenously.
      RESULTS: During the 1st week after transplantation, transplanted cells migrated
      to the lesion and were visible in the lesion on MR images as a hypointensive
      signal, persisting for more than 30 days. In rats with a balloon-induced spinal
      cord compression lesion, we observed an increase in functional recovery and hind
      limb sensitivity after implantation of Endorem-labeled mesenchymal stem cells or
      a freshly prepared mononuclear fraction of bone marrow cells or after injection
      of granulocyte colony-stimulating factor. Morphometric measurements in the center
      of the lesions showed an increase in white matter volume in cell-treated animals.
      Prussian blue staining confirmed a large number of Prussian blue-positive cells,
      and the lesions were considerably smaller than in control animals. CONCLUSIONS:
      These studies demonstrate that magnetic resonance imaging of grafted adult as
      well as embryonic stem cells labeled with iron oxide nanoparticles is a useful
      method for evaluating their migration and fate in CNS.

PMID- 16909040
TI  - Erythropoietin and normal brain development: receptor expression determines multi
      tissue response.
AB  - Erythropoietin (EPO) is a hypoxia-inducible hormone required for erythroid
      differentiation. Expression of the EPO receptor is not restricted to
      hematopoietic cells and exhibits a multi-tissue distribution that includes neural
      cells, vascular endothelium and muscle progenitor cells. The ability for EPO to
      stimulate progenitor cell proliferation and prevent apoptosis is critical for
      maintenance of the erythroid lineage, but is also observed in neural and muscle
      progenitor cells. Mice lacking the EPO receptor die in utero due to severe
      anemia. However, even prior to lack of erythroid cell production in the embryo
      proper, these mice exhibit increased apoptosis in the brain as early as E10.5 and
      a reduction in the number of neural progenitor cells. Corresponding cultures of
      primary neural cells exhibit decreased neuron generation and increased
      sensitivity to reduced oxygen tension, and neurons do not survive after 24 h at
      low oxygen tension. In contrast, hypoxia induces EPO and EPO receptor in wild
      type neuronal cells, and EPO enhances neuron survival at low oxygen tension. In
      vivo EPO is neuroprotective in adult animal models for brain ischemia. Induction
      of EPO and its receptor by hypoxia likely contributes to its neuroprotective
      activity and selective cell survival in the brain during hypoxic stress.

PMID- 16909041
TI  - Wnt signal pathways and neural stem cell differentiation.
AB  - Self-renewal, migration and differentiation of neural progenitor cells are
      controlled by a variety of pleiotropic signal molecules. Members of the morphogen
      family of Wnt molecules play a crucial role for developmental and repair
      mechanisms in the embryonic and adult nervous system. A strategy of disclosure of
      the role of different canonical (glycogen synthase kinase-3beta/beta-catenin
      dependent) and noncanonical (Ca2+- and JNK-dependent) signal pathways for
      progenitor cell expansion and differentiations is illustrated at the example of
      the rat striatal progenitor cell line ST14A that is immortalized by stable
      retroviral transfection with a temperature-sensitive mutant of the SV40 large T
      antigen. A shift from permissive 33 degrees C to nonpermissive 39 degrees C leads
      to proliferation stop and start of differentiation into glial and neuronal cells.
      Investigation of expression of Wnts, Wnt receptors and Wnt-dependent signal
      pathway assay point to a stage-dependent involvement of canonical and
      noncanonical signaling in proliferation and differentiation of ST14A cells,
      whereby a mutual suppression of pathway activities is likely. Canonical Wnt
      molecules are not detected in proliferating and differentiating ST14A cells
      except Wnt2. The noncanonical Wnt molecules Wnt4, Wnt5a and Wnt11 are expressed
      in proliferating cells and increase during differentiation, whereas cellular beta
      catenin decreases in the early phase and is restored in the late phase of
      differentiation. Accumulation of beta-catenin at the membrane in undifferentiated
      proliferating cells and its nuclear localization in nondividing undifferentiated
      cells under differentiation conditions argues for a distinct spatially regulated
      role of the molecule in the proliferation and early differentiation phase. Ca2+
      dependent and JNK-dependent noncanonical Wnt signaling is not detected during
      differentiation of ST14A cells. Complete exploration of the role of Wnt pathways,
      for differentiation of the neural progenitor cells ST14A will require Wnt
      overexpression and exposure of ST14A cells to exogenous Wnts either with purified
      Wnts or by co-cultures with Wnt producers.

PMID- 16909042
TI  - Erythropoietin, a cytoprotective and regenerative cytokine, and the hypoxic
      brain.
AB  - Hypoxia and ischemia in the brain often result in brain dysfunctions and neuronal
      death during both the neonatal and adult periods. Though the mechanisms
      contributing to brain injury secondary to hypoxia-ischemia are more clearly
      defined, there are still no pharmacological treatments available to reduce cell
      death in the ischemic brain. This review highlights the beneficial effects of
      hypoxia-inducible factors, such as the transcriptional factor hypoxia-inducible
      factor-1 and its target genes, as both cytoprotective and regenerative factors,
      and focuses in particular on one of the most well-known: erythropoietin.
      Altogether, the data presented in this review suggest that further insights into
      the role of hypoxia-inducible factors would help develop promising strategies to
      improve the outcome of hypoxia/ischemia-related brain pathologies.

PMID- 16909043
TI  - Induction of signalling in non-erythroid cells by pharmacological levels of
      erythropoietin.
AB  - Erythropoiesis is maintained by the hormone erythropoietin (Epo) binding to its
      cognate receptor (EpoR) on erythroid progenitor cells. The Epo-EpoR interaction
      initiates a signal transduction process that regulates the survival, growth and
      differentiation of these cells. Originally perceived as highly lineage
      restricted, Epo is now recognised to have pleiotropic effects extending beyond
      the maintenance of red cell mass. Functional interactions between Epo and EpoR
      have been demonstrated in numerous cells and tissues. EpoR expression on
      neoplastic cells leads to concern that recombinant human erythropoietin, used to
      treat anaemia in cancer patients, may augment tumour growth. Here we demonstrate
      that EPO, at pharmacological concentrations, can activate three major signalling
      cascades, viz. the Jak2/STAT5, Ras/ERK and PI3K/Akt pathways in non-small cell
      lung carcinoma (NSCLC) cell lines. EpoR synthesis is normally under the control
      of GATA-1, but NSCLC cells exhibit decreased GATA-1 levels compared to GATA-2, -3
      and -6, suggesting that GATA-1 is not essential for EpoR production. The
      increased Epo-induced signalling was not associated with a growth advantage for
      the NSCLC cells.

PMID- 16909044
TI  - Cell transplantation for ischemic stroke.
AB  - Cell replacement therapy has been evaluated as a regenerative strategy for
      patients with fixed neurologic deficits after ischemic stroke. Animal models have
      identified specific cell lines which lead to regeneration and improvement in
      behavior and motor function after implantation into areas of ischemic injury.
      This has led to the development of pilot studies in humans, which have mainly
      investigated the safety and pilot efficacy of such approaches with promising
      early results. As research in this area progresses, further prospective trials
      are necessary not only to demonstrate clinical efficacy but also to understand
      the mechanisms underlying the early positive experiences, to select appropriate
      patients for cell replacement therapy, and to elucidate the optimal timing and
      mode of cell delivery.

PMID- 16909045
TI  - Large-scale analysis of neural stem cells and progenitor cells.
AB  - The past few years have seen remarkable progress in our understanding of stem
      cell biology. The wealth of genomic data and the multiplicity of sources have
      enabled researchers to begin to profile stem cells in detail. In this paper we
      describe the biological and technical controls necessary to obtain reliable data
      and the relative merits of various large-scale analytical techniques including
      microarray, expressed sequence tag enumeration, serial analysis of gene
      expression and massively parallel signature sequencing. We suggest that while
      much has been learned, additional information remains to be gleaned by meta
      analysis of existing data.

PMID- 16909046
TI  - 2-DE proteomic profiling of neuronal stem cells.
AB  - Proteomics has become a powerful tool in neuroscience studies. Although numerous
      human neural stem cells are available for research purposes since many years,
      there exists only limited information on proteomic data from stable neural stem
      cell lines. Profiling and functional proteome studies of neuronal stem cells will
      help to describe the protein inventory as well as protein activity and
      interactions, subcellular localization and posttranslational modifications. The
      proteomic analysis of neuronal differentiation processes will elucidate the
      complex events leading to the generation of different phenotypes via distinctive
      developmental programs that control self-renewal, differentiation, and
      plasticity. Using the ReNcell VM197 model, a cell line derived from human fetal
      ventral mesencephalon stem cells, we studied the protein inventory of the stem
      cells by 2-DE gel electrophoresis and mass spectrometric protein identification
      and constructed a 2-DE protein map consisting of more than 400 identified protein
      spots. This proteome reference database constitutes the basis for further
      investigations of differential protein expression during differentiation. A
      profiling of the neuronal differentiation-associated changes displayed the large
      rearrangement of the proteome during this process, and the proteomic techniques
      proved to be a valuable tool for the elucidation of neuronal differentiation
      process and for target protein screening.

PMID- 16909048
TI  - Evidence of a genetic basis of Morgagni-Stewart-Morel syndrome. A case report of
      identical twins.
AB  - We report two 71-year-old female monozygotic twins presenting with advanced
      hyperostosis frontalis interna, obesity, shortness and cognitive impairment. They
      both have suffered from generalized seizures since their early adulthood.
      Moreover, the patients showed some additional conditions only occurring in one
      individual or the other such as migraine, marked recurrent depressive disorder or
      polyarthrosis. The symptoms common to both twins appear to correspond to the
      Morgagni-Stewart-Morel syndrome and indicate a genetic basis of this disorder as
      these features occur in genetically identical patients.

PMID- 16909047
TI  - Tissue plasminogen activator-induced ischemic injury is reversed by NMDA
      antagonist MK-801 in vivo.
AB  - In vitro studies suggested that tissue plasminogen activator (t-PA) may aggravate
      ischemic injury by enhancing N-methyl-D-aspartate (NMDA) receptor signalling. It
      remained unclear whether NMDA signalling is also relevant for t-PA toxicity in
      vivo. We herein examined effects of intravenous t-PA (10 mg/kg), administered
      alone or in combination with the NMDA antagonist MK-801 (0.2 mg/kg), following 90
      min of middle cerebral artery occlusion in mice. In our study, MK-801 alone,
      administered intraperitoneally, neither affected infarct volume nor brain
      swelling at 24 h after reperfusion. t-PA significantly increased infarct size, in
      accordance with previous findings. t-PA-induced ischemic injury was completely
      abolished and brain swelling markedly reduced when t-PA-treated animals received
      additional MK-801 injections. To elucidate how t-PA influences brain damage, we
      examined actions of t-PA on the expression of NO synthases by
      immunohistochemistry, showing that t-PA does not influence neuronal NO synthase,
      but increases inducible NO synthase in ischemic areas. The effect of t-PA on
      inducible NO synthase levels was completely reversed after cotreatment with MK
      801. Our study provides in vivo evidence in a model of focal cerebral ischemia
      that t-PA-induced brain injury involves an NMDA receptor-dependent mechanism.

PMID- 16909049
TI  - List of drugs in development for neurodegenerative diseases. Update September
      2005.

PMID- 16909050
TI  - Statins, fracture risk, and bone remodeling: What is true?
AB  - Besides the action on plasma lipid levels, statins show a series of ancillary
      effects defined as all of their vascular and nonvascular effects independent from
      the cholesterol reduction. It has been recently hypothesized that one of these
      ancillary effects could be the improvement of bone health, due to the
      interference with bone metabolism. This may potentially represent the rationale
      for statins' use in the treatment of osteoporosis, the most common disease of the
      bone. Both experimental observations and clinical studies on this topic generated
      a number of conflicting results; however, the largest randomized clinical trials,
      the Scandinavian Simvastatin Survival Study (4S), Long Term Intervention with
      Pravastatin in Ischemic Disease (LIPID), and Heart Protection Study (HPS),
      indicate that statins do not prevent or reduce fracture risk.

PMID- 16909051
TI  - Serum cortisol levels in patients admitted to the department of medicine:
      Prognostic correlations and effects of age, infection, and comorbidity.
AB  - BACKGROUND: In contrast to healthy adults or critically ill patients, data on
      serum cortisol levels in noncritically ill patients admitted to general internal
      medicine wards has not been well characterized. We aimed to describe the
      distribution and range of serum cortisol levels in patients admitted to the
      department of medicine, to discover whether old age, severe infections, or
      comorbidity induced a blunted hypothalamic-pituitary-adrenal (HPA) response and
      whether initial serum cortisol value had a prognostic significance. METHODS:
      Morning (8 am) serum cortisol level together with epidemiologic, clinical, and
      laboratory data were analyzed for 252 consecutive adult (age > or = 18 yrs)
      patients admitted to the department of internal medicine during a 6-weeks period.
      RESULTS: The mean serum cortisol level (541 +/- 268 nmol/L) was within the normal
      range. Only one patient had a low serum cortisol level of 72 nmol/L, whereas the
      majority of patients had either normal (80%) or increased (19%) serum cortisol
      levels. Older age, sepsis, prolonged duration of fever, higher comorbidity score,
      and higher serum creatinine level were each associated with significantly higher
      serum cortisol level. In addition, a higher serum cortisol level was
      significantly related to longer hospitalization and higher in-hospital mortality
      rate. CONCLUSIONS: Serum cortisol level positively correlated with age, disease
      severity, and outcome. All admitted patients, except one, had normal to high
      serum cortisol. Whether this increased cortisol level is an adequate HPA response
      or less than required for the disease-induced stress should be investigated in
      further studies.

PMID- 16909052
TI  - Lung function and airway hyperresponsiveness in adult patients with sickle cell
      disease.
AB  - BACKGROUND: Lung disease is a major cause of morbidity and death in sickle cell
      disease. Although airway hyperresponsiveness has been noted in children, there
      are no studies in adult sickle cell patients. The aim of this study was to
      investigate the prevalence of airway hyperresponsiveness in adult sickle cell
      patients. METHODS: Twenty-six patients with sickle cell disease (10 HbSC, 9 HbSS,
      and 7 HbSbeta) were compared with 28 normal control subjects. Pulmonary function
      tests, including spirometry, measurements of single-breath diffusing capacity and
      the methacholine challenge test were performed. RESULTS: There were no
      significant differences in age, gender, or height between groups. Restrictive
      ventilatory defect was observed in six patients (24%) in the sickle cell disease
      group. Obstructive ventilatory defect and reduced diffusing lung DLCO capacity
      was observed in all sickle cell disease subgroups. A positive methacholine
      challenge test was obtained in eight (31%) sickle cell patients and in two of the
      28 controls (7%). CONCLUSION: These features suggest that there is a high
      prevalence of airway hyperresponsiveness in adult patients with sickle cell
      disease without a history of reactive airway disease.

PMID- 16909053
TI  - Preventing oxidative stress in rats with aldosteronism by calcitriol and dietary
      calcium and magnesium supplements.
AB  - BACKGROUND: Prominent features of the clinical syndrome of congestive heart
      failure (CHF) include aldosteronism and the presence of oxidative stress.
      Secondary hyperparathyroidism (SHPT) accompanies aldosteronism due to increased
      urinary and fecal excretion of Ca. SHPT accounts for intracellular Ca overloading
      of diverse cells, including peripheral blood mononuclear cells (PBMC), and the
      appearance of oxidative stress. Parathyroidectomy or a Ca channel blocker each
      prevent these responses. Herein, we hypothesized calcitriol, or 1,25(OH)2D3, plus
      a diet supplemented with Ca and Mg (CMD) would prevent SHPT and Ca overloading of
      PBMC and thereby oxidative stress in these cells in rats receiving
      aldosterone/salt treatment (ALDOST). METHODS AND RESULTS: In rats with ALDOST for
      4 weeks, without or with CMD, we monitored plasma-ionized [Ca]o and parathyroid
      hormone (PTH), and PBMC cytosolic-free [Ca]i and H2O2 production. Untreated, age-
      and gender-matched rats served as controls. Compared to controls, ALDOST led to
      an expected fall in plasma [Ca]o level with accompanying rise in plasma PTH level
      and intracellular Ca overloading of PBMC and their increased production of H2O2.
      CMD prevented SHPT and abrogated intracellular Ca overloading of PBMC and their
      increased H2O2 production. CONCLUSIONS: The appearance of SHPT in aldosteronism,
      induced by fallen plasma [Ca]o, leads to PTH-mediated Ca overloading of PBMC and
      their increased production of H2O2. SHPT in rats with aldosteronism can be
      prevented by calcitriol and a diet supplemented with Ca and Mg. These findings
      raise the prospect that the SHPT found in CHF could be managed with macro- and
      micronutrients.

PMID- 16909054
TI  - Coronary artery fistulae.
AB  - Coronary artery fistulae are abnormal communications between a coronary artery
      and a cardiac chamber or major vessel (vena cava, pulmonary veins, pulmonary
      artery). They are usually diagnosed by coronary arteriography. Clinical
      presentations are variable depending on the type of fistula, shunt volume, site
      of the shunt, and presence of other cardiac conditions. In this article, we
      review the literature regarding etiology, incidence, clinical manifestation,
      image studies, and management.

PMID- 16909055
TI  - Pylephlebitis associated with acute infected choledocholithiasis.
AB  - Pylephlebitis, also called septic thrombophlebitis of the portal vein, is a life
      threatening complication of intra-abdominal infection. Although rare, it remains
      a less recognized entity with a high rate of mortality. We present a 66-year-old
      man with acute infected choledocholithiasis complicated with Bacteroides fragilis
      bacteremia. The contrast-enhanced computed tomography scan of the abdomen showed
      nearly total thrombotic occlusion of the left portal vein. The comprehensive
      studies for hypercoagulation disorders all yielded negative results. After
      endoscopic extraction of bile duct stones and broad-spectrum antibiotic therapy,
      the patient recuperated with complete recanalization of the occluded portal vein.
      To our knowledge, pylephlebitis associated with acute infected
      choledocholithiasis has never been reported. This report details the clinical
      features, radiographic findings, pathogenesis, and treatment of this distinctly
      unusual manifestation. Early identification of pylephlebitis and underlying intra
      abdominal infection can be achieved by exquisite imaging studies with raised
      awareness in the clinical setting. Eradication of infectious foci and judicious
      administration of antimicrobials are essential to reduce the catastrophic
      morbidity and mortality of pylephlebitis.

PMID- 16909056
TI  - Rhabdomyolysis and acute renal failure associated with influenza virus type B
      infection.
AB  - A patient with rhabdomyolysis-induced acute renal failure due to influenza B
      virus infection is presented. Influenza B infection caused rhabdomyolysis with
      efflux of myoglobin from myocytes, causing acute renal failure. In conclusion,
      influenza virus type B can cause severe rhabdomyolysis leading to acute renal
      failure.

PMID- 16909057
TI  - Syphilis mimicking Reiter's syndrome in an HIV-positive patient.
AB  - A 38-year-old man with HIV infection presented with panuveitis, urethritis, and a
      papulosquamous eruption on his palms and soles. Careful physical and laboratory
      examination led to the diagnosis of syphilitic keratoderma, uveitis, and
      balanitis. The patient was successfully treated with penicillin and prednisone
      therapy. Because the initial presentation was difficult to distinguish from the
      symptoms of Reiter's syndrome, a high degree of clinical suspicion was required
      to accurately diagnose syphilis, a curable and potentially fatal disease.

PMID- 16909058
TI  - Resolution of intractable hiccups after near-infrared irradiation of relevant
      acupoints.
AB  - BACKGROUND: Intractable hiccups are occasionally encountered in the presence of
      stroke but are usually difficult to manage. METHODS: We describe two stroke
      patients with intractable hiccups that were refractory to pharmacological
      treatment but were well resolved by application to relevant acupoints with the
      modality linear polarized near-infrared ray equipment on PC 6 (Nei Guan), ST 36
      (Zu San Li), and DU 9 (Chih Yang), which are the empirical acupoints aimed at
      regulating gastrointestinal mobility and function of the thoracic organ. RESULTS:
      The first patient who received the treatment for only one time came out with a
      dramatic termination of intractable hiccups 3 hours later and with no recurrence
      thereafter. We applied the same treatment on the second patient once a day for 8
      consecutive days, which led to progressive amelioration of intractable hiccups.
      CONCLUSIONS: This is the first report about the complete resolution of
      intractable hiccups due to stroke using near-infrared irradiation to acupoints,
      rather than using conventional pharmacologic therapy, traditional acupuncture, or
      moxibustion. Consequently, these findings suggest that linear polarized near
      infrared ray irradiation, with its noninvasive properties, might be an
      alternative treatment for intractable hiccups after stroke.

PMID- 16909059
TI  - Brugada-type electrocardiographic changes in a febrile patient of african
      descent.
AB  - Brugada syndrome is an arrhythmic syndrome characterized by a pattern of right
      bundle branch block and an ST-segment elevation in the right precordial leads on
      the electrocardiogram. This type of electrocardiographic change is predominantly
      documented in Asian and white persons and almost never present in persons of
      African ancestry. Despite the well-known risk of sudden death in patients with
      Brugada syndrome, controversy exists concerning the management of asymptomatic
      patients with Brugada-type electrocardiographic patterns. The present report
      describes the case of a patient with a Brugada-type electrocardiographic pattern
      induced by his febrile condition. A favorable outcome was achieved with a
      conservative approach.

PMID- 16909060
TI  - Pneumatosis cystoides intestinalis with systemic sclerosis, limited type
      resulting in a poor prognosis.
AB  - Pneumatosis cystoides intestinalis (PCI) is a rare disease characterized by the
      presence of multilocular intramural clusters of gas in the alimentary tract and
      has been considered to have a favorable response to conservative treatment. We
      describe the first case of limited type of systemic sclerosis (SSc) with PCI. A
      74-year-old Japanese woman presented with a 4-month history of an unhealed
      cutaneous ulcer on the right third finger, along with sclerodactyly of bilateral
      hands. Proximal skin sclerosis was absent. The patient reported acute abdominal
      pain, and a diagnosis of PCI was established on plain radiography. The patient
      died of multiple organ failure 5 months after the development of PCI. PCI is
      rarely complicated with SSc, and all cases previously reported were associated
      with diffuse SSc. Because PCI is one of the poor prognostic factors of SSc, we
      should recognize the presence of this condition even in patients with limited
      cutaneous involvement.

PMID- 16909061
TI  - Rhabdomyolysis associated with hyperthyroidism.
AB  - BACKGROUND: Nontraumatic rhabdomyolysis has been associated with alcohol and drug
      abuse, seizures, strenuous exercise, muscle hypoperfusion, hyperthermia,
      electrolyte disturbances, diabetic coma, and hypothyroidism. Hyperthyroidism can
      be associated with several neuromuscular manifestations, such as thyrotoxic
      myopathy and thyrotoxic periodic paralysis, both associated with weakness and
      normal creatine phosphokinase levels. There have been only three reported cases
      of rhabdomyolysis as a result of thyrotoxicosis. We are reporting the fourth case
      of such association. CASE REPORT: The patient is a 26-year-old black woman with
      history of hypertension. She presented to the clinic with blurred vision,
      headaches, palpitations, weight loss, weakness, and persistent high blood
      pressure. She was found to have exophthalmus, lid lag, and a symmetric, smooth,
      and diffuse goiter. Ptosis and diplopia were absent; neurologic examination
      findings was normal. The patient had positive TPO antibodies, elevated free T4
      level, and low thyroid-stimulating hormone (TSH) level. Graves disease was
      diagnosed and propylthiouracil was prescribed. The patient then returned to the
      clinic 2 weeks later with weakness and myalgias. Her physical examination
      findings were unchanged except for mild muscle weakness. Laboratory evaluation
      showed normal electrolytes, normal renal function, and negative urine drug
      screening. Creatine phosphokinase was 1276 U/L. Her free T4 and T3 levels were
      elevated and TSH level was low. The patient was treated with aggressive oral
      fluid resuscitation. Propylthiouracil was continued and free T4 and T3 normalized
      along with creatine phosphokinase with resolution of symptoms. CONCLUSIONS:
      Hyperthyroidism may, theoretically, cause rhabdomyolysis by means of increasing
      energy consumption associated with depletion of muscle energy stores and
      substrates. Our patient constitutes the fourth reported case of rhabdomyolysis
      associated with hyperthyroidism.

PMID- 16909062
TI  - Rating scales, scales of measurement, issues of reliability: resolving some
      critical issues for clinicians and researchers.
AB  - We focus upon several broad issues that are of concern to clinicians and clinical
      researchers in the areas of biobehavioral and biomedical research, including, but
      not limited to, the fields of psychiatry, psychology, neuropsychology, and
      neurology. These issues are the critical reassessment of S. S. Stevens'
      quadripartite conceptualization of scales of measurement; the application of
      criteria to determine the clinical significance of reliability estimates; the
      detection of subsets of reliable and unreliable raters, when the overall level is
      of little clinical import; and finally, the application of Kappa statistics when
      multiple raters evaluate a single case.

PMID- 16909063
TI  - Diagnosing major depressive disorder VI: performance of an objective test as a
      diagnostic criterion.
AB  - Considerable research has evaluated biological and psychological tests for
      various psychiatric disorders; however, few objective tests are included in DSM
      IV as diagnostic criteria. It was recently suggested that existing tests are
      insufficiently accurate to be included as diagnostic criteria. While it is true
      that there are limitations in the sensitivity and/or specificity of such tests,
      this should not rule them out as effective diagnostic criteria. Studies examining
      the diagnostic efficiency of the DSM criteria sets demonstrate that the
      individual criteria vary in their sensitivity and specificity. In the present
      article, we suggest that the same standard should be applied to the evaluation of
      objective tests. That is, we suggest changing the perspective used to evaluate
      the performance of biological and psychological measures from the traditional one
      examining them as diagnostic tests to one in which these measures are evaluated
      as diagnostic criteria. To our knowledge, no previous investigators have compared
      the psychometric performance of an objective test to the psychometric performance
      of the DSM-IV symptom criteria. The recent report from the committee to develop a
      research agenda for the initial planning phase for DSM-V discussed the use of
      self-report symptom scales as possible diagnostic criteria in nonpsychiatric
      settings. In the present report from the Rhode Island Methods to Improve
      Diagnostic Assessment and Services project, we examined the performance of a self
      report depression questionnaire as a diagnostic criterion for major depressive
      disorder (MDD). We compared the performance of the Diagnostic Inventory for
      Depression to the performance of the DSM-IV MDD symptom criteria in 1138
      psychiatric outpatients. The results indicated that the diagnostic efficiency of
      the Diagnostic Inventory for Depression was similar to the loss of interest or
      pleasure criterion, and superior to all of the remaining DSM-IV MDD symptom
      criteria except low mood. We discuss issues related to the possible use of a self
      administered depression symptom scale as a diagnostic criterion.

PMID- 16909064
TI  - Determinants of functional disability and social adjustment in major depressive
      disorder: a prospective study.
AB  - We examined prospectively factors influencing social and occupational disability
      and social adjustment among patients with major depressive disorder. The Vantaa
      Depression Study comprises a cohort of psychiatric inpatients and outpatients
      with major depressive disorder in the city of Vantaa, Finland. We prospectively
      interviewed 193 of 269 (72%) patients both 6 and 18 months after baseline. Axis I
      and II diagnoses were assessed via semistructured WHO Schedules for Clinical
      Assessment in Neuropsychiatry 2.0 and SCID-II interviews. Global disability and
      social and work adjustment were assessed. Patients' functional disability and
      social adjustment were alleviated concurrently with recovery from depression
      during the follow-up. The current level of functioning and social adjustment of a
      patient with depression was predicted by severity of depression, recurrence
      before baseline and during follow-up, lack of full remission, and time spent
      depressed. Comorbid psychiatric disorders, personality traits (neuroticism), and
      perceived social support had significant influence.

PMID- 16909065
TI  - Psychiatric comorbidity is associated with drug use and HIV risk in syringe
      exchange participants.
AB  - The present study evaluated the effects of psychiatric comorbidity on substance
      use disorder prevalence, HIV risk behavior, and other problem severity in male
      and female out-of-treatment injection drug users newly registered at a syringe
      exchange program. Participants (N = 338) were administered the Structured
      Clinical Interview for the DSM-IV, the Addiction Severity Index, and the Risk
      Assessment Battery, and classified into one of four diagnostic groups: (1) no
      antisocial personality disorder (APD) or Axis I psychiatric disorder (N = 162),
      (2) APD only (N = 74), (3) Axis I psychiatric disorder only (N = 55), or (4) APD
      plus Axis I psychiatric disorder (N = 47). Psychiatric comorbidity was associated
      with higher rates of substance use disorder and more HIV risk and other problem
      severity. In general, participants with both APD and an Axis I disorder exhibited
      the most problem severity. APD was uniquely associated with higher prevalence for
      each substance use disorder assessed in this study and with elevated HIV risk.
      These results support and extend studies conducted with opioid-dependent
      individuals recruited from treatment and community settings, and reinforce the
      need to develop interventions to encourage syringe exchange program participants
      to enroll in treatment.

PMID- 16909066
TI  - Depression and ethnicity as intermediary variables among dissociation, trauma
      related cognitions, and PTSD symptomatology in youths.
AB  - The study of childhood posttraumatic stress disorder (PTSD) has grown in recent
      years, and several variables have been closely linked to the etiology of this
      condition. Prominent examples include dissociation, trauma-related cognitions,
      and depression, but no empirically based model regarding these variables has been
      presented. We examined 90 adolescents housed in a state-run facility for youths
      who experienced maltreatment, violence, and/or other traumas. Utilizing
      psychometrically strong dependent measures, we identified a structural equation
      model with depression as a key mediating variable between (1) dissociation and
      trauma-related cognitions and (2) PTSD symptomatology. In addition, African
      American status was found to weaken this relationship, whereas multiracial status
      was found to strengthen this relationship. These results are discussed within the
      context of contemporary integrative theories regarding the developmental
      psychopathology of PTSD in youths.

PMID- 16909067
TI  - The impact of personal threat on police officers' responses to critical incident
      stressors.
AB  - The relationship of type of critical incident (CI) stressor with peritraumatic
      responses and posttraumatic stress disorder symptoms was examined in police.
      Officers (N = 662) provided narratives of their most distressing CI experienced
      during police service and completed measures of related peritraumatic responses
      and posttraumatic stress disorder symptoms. Narratives were reliably rated (kappa
      = .80-1.0) on seven categories emerging from a series of factor analyses of a
      measure of critical incident stressors. Additional analysis revealed that the
      classification of primary narrative features required only five categories
      (personal life threat, duty-related violence, encountering physical or sexual
      assault victims, exposure to civilian death, other). When analyzed by further
      collapsing these five categories into high versus low personal threat, officers
      whose narratives contained high personal threat reported more peritraumatic
      dissociation, peritraumatic emotional distress, and current hyperarousal
      symptoms. Results suggest that greater personal threat during a CI may place an
      officer at greater risk for subsequent distress.

PMID- 16909068
TI  - Recognition of co-occurring medical conditions among patients with serious mental
      illness.
AB  - We determined whether patients with serious mental illness (SMI) were less likely
      than non-SMI to self-report having a medical condition that was recorded in their
      medical record. We included all patients from the VA National Psychosis Registry
      diagnosed with SMI and a random sample of non-SMI patients in fiscal year 1999
      who completed the Large Health Survey of Veteran Enrollees (N = 35,837). Among
      patients with diagnoses for any of 11 conditions recorded in administrative data,
      we evaluated whether patients reported having that same condition in the survey,
      using multivariable logistic regression and generalized estimating equations.
      Among patients diagnosed with a given condition, those with SMI were less likely
      to report being told by providers that they had seven of the 11 conditions
      examined: heart disease (OR = 0.68, p < 0.001), arthritis (OR = 0.79, p < 0.001),
      cancer (OR = 0.69, p < 0.001), diabetes (OR = 0.79, p < 0.001), back pain (OR =
      0.81, p < 0.001), congestive heart failure (OR = 0.71, p < 0.001), and
      hypertension (OR = 0.77, p < 0.001). Patients with SMI were less aware of co
      occurring medical conditions.

PMID- 16909069
TI  - Discriminating between cognitive and supportive group therapies for chronic
      mental illness.
AB  - This descriptive and comparative study employed a Q-sort process to describe
      common factors of therapy in two group therapies for inpatients with chronic
      mental illness. While pharmacological treatments for chronic mental illness are
      prominent, there is growing evidence that cognitive therapy is also efficacious.
      Groups examined were part of a larger study comparing the added benefits of
      cognitive versus supportive group therapy to the treatment milieu. In general,
      items described the therapist's attitudes and behaviors, the participants'
      attitudes and behaviors, or the group interactions. Results present items that
      were most and least characteristic of each therapy and items that discriminate
      between the two modalities. Therapists in both groups demonstrated good therapy
      skills. However, the cognitive group was described as being more motivated and
      active than the supportive group, indicating that the groups differed in terms of
      common as well as specific factors of treatment.

PMID- 16909070
TI  - Violence and abuse among HIV-infected women and their children in Zambia: a
      qualitative study.
AB  - HIV and violence are two major public health problems increasingly shown to be
      connected and relevant to international mental health issues and HIV-related
      services. Qualitative research is important due to the dearth of literature on
      this association in developing countries, cultural influences on mental health
      syndromes and presentations, and the sensitive nature of the topic. The study
      presented in this paper sought to investigate the mental health issues of an HIV
      affected population of women and children in Lusaka, Zambia, through a systematic
      qualitative study. Two qualitative methods resulted in the identification of
      three major problems for women: domestic violence (DV), depression-like syndrome,
      and alcohol abuse; and children: defilement, DV, and behavior problems. DV and
      sexual abuse were found to be closely linked to HIV and alcohol abuse. This study
      shows the local perspective of the overlap between violence and HIV. Results are
      discussed in relation to the need for violence and abuse to be addressed as HIV
      services are implemented in sub-Saharan Africa.

PMID- 16909071
TI  - From emotional abuse in childhood to psychopathology in adulthood: a path
      mediated by immature defense mechanisms and self-esteem.
AB  - The present study examined the course traveled from childhood emotional abuse to
      adulthood psychopathology. One hundred ninety-six undergraduate students age 20
      to 45 (M = 27; SD = 8.17), answered self-report questionnaires assessing
      emotional abuse in childhood (Childhood Trauma Questionnaire), parental attitudes
      (Parental Bonding Instrument), psychopathological symptomatology (Brief Symptom
      Inventory), self-esteem (Rosenberg Self-Esteem Scale), and defense mechanism
      organization (Defense Style Questionnaire). Results indicated that reported
      psychopathological symptomatology highly exceeded the Israeli norm. Structure
      Equation Modeling provided a statistically significant explanation (52%) of the
      target variable of psychopathological symptomatology. According to the path
      model, emotional abuse in childhood and perceptions of controlling and noncaring
      parents had an indirect effect on the psychopathology. This was mediated by
      immature defenses and low self-esteem. We conclude that the manifest
      psychopathology among adults who suffered emotional abuse in childhood is
      produced by the detrimental effect of abuse on personality, and takes the form of
      immature defense organization and damaged self-representation.

PMID- 16909072
TI  - Public knowledge about causes and treatment for schizophrenia: a representative
      population study.
AB  - Research on public knowledge about schizophrenia has so far examined various
      closed questions eliciting recognition-based knowledge rather than unprompted
      knowledge. We aim to explore the unprompted popular knowledge regarding causes
      and treatment of schizophrenia. In a representative survey conducted in Germany
      in 2001 (N = 5025), two open questions asked respondents to name possible causes
      and treatment options for schizophrenia. Answers were noted down verbatim and
      later grouped into categories. Psychosocial and biological causal explanations
      were equally predominant. Respondents recommended drug treatment more frequently
      than psychosocial measures like psychotherapy, and they mentioned a doctor's
      visit or a hospital stay most frequently as the adequate treatment setting. About
      45% of respondents knew nothing about possible causes or treatments of
      schizophrenia. Hence, whereas those confidently naming causes or treatment
      options for schizophrenia favored professional medical treatment more than
      previously found, overall knowledge about schizophrenia has thus far been
      overestimated.

PMID- 16909073
TI  - Procedural memory predicts social skills in persons with schizophrenia.
AB  - Despite a growing number of studies that have investigated the relationship
      between neurocognition and psychosocial outcome in schizophrenia, no studies have
      looked at the relationship between procedural memory and social skills measures
      in schizophrenia. The goal of this study was to investigate whether procedural
      memory, often preserved in schizophrenia, could predict nonverbal social skills
      in chronic patients with schizophrenia. Fourteen outpatients with schizophrenia
      participated in our study. Procedural memory was evaluated using the Mirror
      Reading Test, and nonverbal and verbal social skills were evaluated using a
      structured role play test. As predicted, there was a significant positive
      correlation between the learning index of the Mirror Reading Test and nonverbal
      skills (Spearman rho=0.559, p = 0.038), but not for verbal communication skills
      or processing skills. Although preliminary, these results provide the first
      evidence of an association between procedural memory and nonverbal social skills
      in patients with schizophrenia.

PMID- 16909074
TI  - The persecutory ideation questionnaire.
AB  - We report the development and evaluation of a brief questionnaire measure of
      persecutory ideation, the Persecutory Ideation Questionnaire (PIQ). Our approach
      was theoretically driven in that the PIQ was constructed in accordance with
      comprehensive definitional considerations and criteria set out by . Sixty-six
      more general paranoia-related items were accumulated, and 10 independent raters
      sorted the items into two sets, "persecutory ideation" and "other." An 80%
      agreement criterion was set, resulting in 10 persecutory ideation items. The PIQ
      was evaluated with a nonclinical and a clinical sample. In both samples, it was
      shown to have excellent reliability (internal consistency) and excellent
      convergent validity as a measure of certain aspects of general paranoid ideation.
      Finally, the PIQ shared unique variance with severity of persecutory delusions in
      the clinical group, providing good criterion validity for the PIQ as a measure of
      specifically persecutory ideation, rather than paranoia in general.

PMID- 16909075
TI  - Beating the beat: reading can be faster than the frequency of eye movements in
      persons with congenital nystagmus.
AB  - PURPOSE: Rapid serial visual presentation (RSVP) of text has been reported to
      foster higher reading rates than presentation in a continuous text (CT) format,
      possibly because scanning eye movements are minimized. We investigated how this
      might be relevant for persons with congenital nystagmus (CN). METHODS: We
      evaluated whether reading rates differ in persons with CN for RSVP versus CT
      presentation of single sentences under otherwise similar conditions. In a second
      experiment, we presented unrelated words to observers with CN in RSVP format
      while measuring their eye movements to determine whether reading can occur during
      the high-velocity, nonfoveating periods of the CN wave form. Both sentences and
      random words were selected from the MNRead corpus and displayed at 2x, 4x, or 8x
      the threshold word size on a 21-inch computer monitor. RESULTS: Subjects with CN
      have virtually equivalent maximum reading speeds of 449 and 448 words per minute,
      respectively, for RSVP and CT presentation of sentences. Typically, reading rates
      were faster than the frequency of CN, which suggests that subjects could read
      during the nonfoveating periods of the nystagmus waveform. This finding was
      confirmed using random words that, unlike those in sentences, cannot be inferred
      from contextual cues. Examination of eye movements recorded during reading
      indicated that random words are read correctly with 47% to 65% accuracy
      (depending on word size) during the nonfoveating periods of the CN waveform.
      CONCLUSION: A clinical implication of these results is that reading performance
      in persons with CN should be facilitated by large text sizes that remain legible
      during a greater fraction of the CN waveform.

PMID- 16909077
TI  - Toward greater access.

PMID- 16909076
TI  - Is the Cardiff Acuity Test effective in detecting refractive errors in children?
AB  - PURPOSE: Refractive error is a common cause of reduced visual acuity in young
      children. This reduced vision should be detected as soon as possible to avoid
      development of squinting and educational disadvantage. The Bailey-Lovie Chart
      (BLC) is based on the logarithm of the minimal angle of resolution (logarithm of
      the minimum angle of resolution logMAR) and is widely accepted as the clinical
      standard for visual acuity testing. However, most young children are unable to
      perform this test because of its symbolic level. The Cardiff Acuity Test (CAT)
      overcomes these symbolic demands and is the test of choice for young children in
      most U.K. orthoptic departments. The purpose of this study is to determine how
      effective the CAT is in detecting reduced visual acuity caused by refractive
      error in young children. METHODS: Visual acuity of the right eye was tested
      without spectacles in 68 children (mean age, 74 +/- 14.6 months) with known
      bilateral symmetric refractive error (40 male) using the CAT and the BLC.
      Subjects were randomized to receive CAT or BLC first in a single assessment using
      a crossover design. Subjects scoring 0.2 logMAR or better were classified as
      having passed the test. RESULTS: The CAT correctly identified reduced vision
      caused by uncorrected refractive error in 25% (17) of the children compared with
      a detection rate of 97% (66) for the BLC using the specified pass criteria.
      Further analysis with an adjusted cut point for the CAT (0.0 logMAR), as used to
      identify abnormal vision in clinical practice, identified a detection rate of 56%
      (38 of the children). CONCLUSIONS: This study casts doubt on the current clinical
      practice used in orthoptic clinics by suggesting that assessment of visual acuity
      with the CAT alone will underdiagnose reduced acuity caused by refractive errors.

PMID- 16909078
TI  - Statins are found to help prevent cataracts.

PMID- 16909080
TI  - Successful treatment of retinal angiomatous proliferation by photodynamic
      therapy.
AB  - PURPOSE: The purpose of this study is to describe a patient with retinal
      angiomatous proliferation (RAP) treated successfully by photodynamic therapy.
      METHODS: A 74-year-old white woman was referred to our clinic for evaluation as a
      result of progressive decrease of vision in the right eye. Visual acuity was
      20/100 in the affected right eye. The findings of fluorescein and indocyanine
      green angiography were consistent with a diagnosis of RAP, and cystoid macular
      edema was also revealed by optical coherence tomography (OCT). Photodynamic
      therapy (PDT) was carried out because of visual deterioration and localization of
      the RAP. RESULTS: The RAP was treated with PDT, and an improvement in visual
      acuity to 20/60 was noted 4 months after treatment and 20/40 after 6 months. The
      resolution of the lesion was confirmed by fluorescein angiography, indocyanine
      green angiography, and OCT. CONCLUSIONS: Photodynamic therapy can be effective
      for the treatment of RAP when it is associated with visual acuity decrease and is
      located near the fovea.

PMID- 16909082
TI  - The repeatability of MNREAD acuity charts and variability at different test
      distances.
AB  - PURPOSE: The purposes of this study are to establish the repeatability of the
      MNREAD acuity charts in a normal adult population and to determine the
      coefficient of repeatability for reading acuity, reading speed, and critical
      print size. The study also investigates how changing the working distance affects
      these parameters. METHODS: Thirty normal young adults (mean age, 23.3 years)
      participated. Test-retest repeatability was assessed at 40 cm over two sessions
      by the same examiner using MNREAD charts 1 and 2. Additional measurements were
      also carried out at 24 cm and 52 cm working distances. The distance and the
      version of the chart used were randomized. RESULTS: The coefficient of
      repeatability was found to be +/- 0.05 logarithm of the minimum angle of
      resolution (logMAR) for reading acuity, +/- 0.12 logMAR for critical print size,
      and +/- 8.6 words per minute for reading speed. Reading acuity and critical print
      size changed significantly with testing distance (p = 0.001). No changes were
      found in the reading speed at the different test distances (p = 0.27).
      CONCLUSIONS: The MNREAD acuity charts can be used reliably to measure reading
      acuity, reading speed, and critical print size in a normal adult population.

PMID- 16909081
TI  - Gaze behavior of the visually impaired during street crossing.
AB  - PURPOSE: This study explored the gaze patterns of fully sighted and visually
      impaired subjects during the high-risk activity of crossing the street. METHODS:
      Gaze behavior of 12 fully sighted subjects, nine with visual impairment resulting
      from age-related macular degeneration and 12 with impairment resulting from
      glaucoma, was monitored using a portable eye tracker as they crossed at two
      unfamiliar intersections. RESULTS: All subject groups fixated primarily on
      vehicles and crossing elements but changed their fixation behavior as they moved
      from "walking to the curb" to "standing at the curb" and to "crossing the
      street." A comparison of where subjects fixated in the 4-second time period
      before crossing showed that the fully sighted who waited for the light to change
      fixated on the light, whereas the fully sighted who crossed early fixated
      primarily on vehicles. Visually impaired subjects crossing early or waiting for
      the light fixate primarily on vehicles. CONCLUSIONS: Vision status affects
      fixation allocation while performing the high-risk activity of street crossing.
      Crossing decision-making strategy corresponds to fixation behavior only for the
      fully sighted subjects.

PMID- 16909083
TI  - Quantification of refractive error: comparison of autorefractor and focometer.
AB  - PURPOSE: The advantages of a focometer (FOCOMETER) over other methods of
      refraction for use in developing countries are that it is lightweight, compact,
      relatively inexpensive, fairly quick, and easy to use with minimal training. This
      clinical trial compared the repeatability, validity, and ease of use of the
      focometer with an autorefractor. METHODS: The refractive status of the right eye
      of 80 participants was determined with an autorefractor (Canon RK3). Three
      measurements were also taken with the focometer. RESULTS: The spherical
      equivalent (M) of the focometer was 0.25 D more positive than the autorefractor
      (p < 0.001) and 84% of measurements were within 0.75 D of the autorefractor. The
      autorefractor detected astigmatism in 91% (73) of the eyes, whereas the focometer
      identified only 32% (26). The design of the clock target restricts cylinder axis
      accuracy to the nearest 15 degrees . There was evidence of a learning effect for
      the focometer: the second and third measurements were more repeatable in the
      untrained group. There were no differences between the mean (1.03 +/- 2.28) and
      third focometer (-1.05 +/- 2.32) measurements (p = 0.34). However, using the
      third focometer measurement, 94% of participants had visual acuities of at least
      6/12(-2). CONCLUSIONS: This study highlighted the focometer's restricted power
      range, inaccuracy of astigmatism and axis determination, and dependence on
      subject understanding and compliance. Therefore, in most clinical settings, the
      focometer would not be adequate for quantifying refractive error, but the
      focometer spherical equivalent was within acceptable limits of the autorefractor,
      and the visual acuity with lenses determined by the focometer indicates its
      potential usefulness in public health settings, especially where only spherical
      ready-made spectacles are dispensed. There may be more cost-effective ways to
      determine refractive error in these circumstances. A potentially important
      enhancement in focometer methodology that improves its ease of use was
      identified: use only the third measurement for each eye.

PMID- 16909084
TI  - Effect of aging on stereoscopic interocular correlation.
AB  - PURPOSE: This study was designed to evaluate the minimum interocular correlation
      (IOC) needed by the visual system to correctly perceive a static stereoscopic
      stimulus as a function of normal aging. It was also our goal to evaluate the
      feasibility of clinical charts testing this aspect of visual perception. METHODS:
      Stereoscopic IOC threshold was determined in 100 normal observers (average age +/
      standard deviation, 45.7 +/- 20.4 years) drawn from a clinical population
      between the ages of 10 and 85. We used partially correlated red-green random dot
      stereograms (RDS) displaying flat, square surfaces at 360 arcsec of either
      crossed or uncrossed disparity. RESULTS: Older observers needed a higher
      binocular correlation to perceive the stereoscopic stimuli when compared with the
      younger groups. There is a slight increase in the threshold value of the
      individuals in the 45- to 64-year-old group and a further effect on the observers
      over 65 years of age. Data did not reveal any effects of gender, near point
      phoria, or fixation disparity on IOC thresholds. CONCLUSIONS: Normal aging
      produces a statistically significant deficit in binocular correlation processing.
      This process is marginally correlated with stereo acuity measures even when
      stereoacuity floor effects are factored out. Although further experiments
      directly comparing stereoacuity and IOC are necessary and more refining is
      required to obtain optimum parameters, clinical stereoscopic IOC test charts
      appear feasible and may not assess the same processes as stereoacuity charts.

PMID- 16909086
TI  - Corneal asphericity and visual function after wavefront-guided LASIK.
AB  - PURPOSE: In recent years, a theory has been advanced that corneal asphericity in
      and of itself determines visual function; that the natural, optimal shape of the
      cornea is prolate; and that changing the cornea from prolate to oblate negatively
      impacts visual results. This article presents an analysis of the impact of
      corneal asphericity on wavefront-guided LASIK. METHOD: A retrospective analysis
      was conducted of 160 myopic eyes that had undergone wavefront-guided LASIK.
      Surgical procedures and data collection were conducted at six clinical sites.
      Corneal topography, visual acuity, and contrast sensitivity data were collected
      before and 6 months after surgery. The topographically measured corneal surface
      of each eye was fitted to a conic, and a Q-value was computed for a 5.5-mm pupil.
      Multivariate regression analysis was performed to evaluate the correlation
      between Q-value and visual function. The relationship of changes in the corneal
      surfaces to visual performance was also investigated. RESULTS: Preoperative
      corneas exhibited negative (prolate) conic shape constants. Postoperative corneas
      were about equally divided between positive (oblate) and negative conics. There
      was no statistically significant correlation between corneal shape and visual
      acuity or contrast sensitivity function. Changes in corneal asphericity after
      surgery had no significant correlation with changes in visual acuity or contrast
      sensitivity. CONCLUSION: Visual acuity and contrast sensitivity after wavefront
      guided LASIK are not dependent on corneal asphericity. Neither preserving nor
      inducing asphericity ensures better visual outcome. Better visual outcomes are
      more likely to result from the application of a customized shape than a standard
      conic shape.

PMID- 16909085
TI  - The Study of Progression of Adult Nearsightedness (SPAN): design and baseline
      characteristics.
AB  - PURPOSE: The Study of Progression of Adult Nearsightedness (SPAN) is a 5-year
      observational study to determine the risk factors associated with adult myopia
      progression. Candidate risk factors include: a high proportion of time spent
      performing near tasks, performing near tasks at a close distance, high
      accommodative convergence/accommodation (AC/A) ratio, and high accommodative lag.
      METHODS: Subjects between 25 and 35 years of age, with at least -0.50 D spherical
      equivalent of myopia (cycloplegic autorefraction), were recruited from the
      faculty and staff of The Ohio State University. Progression is defined as an
      increase in myopia of at least -0.75 D spherical equivalent as determined by
      cycloplegic autorefraction. Annual testing includes visual acuity, noncycloplegic
      autorefraction and autokeratometry, phoria, accommodative lag, response AC/A
      ratio, cycloplegic autorefraction, videophakometry, ultrasound, and partial
      coherence interferometry (IOLMaster). Participants' near activities were assessed
      using the experience sampling method (ESM). Subjects carried a pager for two 1
      week periods and were paged randomly throughout the day. Each time they were
      paged, they dialed into an automated telephone survey and reported their visual
      activity at that time. From these responses, the proportion of time spent
      performing near work was estimated. RESULTS: Three-hundred ninety-six subjects
      were enrolled in SPAN. The mean (+/- standard deviation) age at baseline was 30.7
      +/- 3.5 years, 66% were female, 80% were white, 11% were black, and 8% were
      Asian/Pacific Islander. The mean level of myopia (spherical equivalent) was -3.54
      +/- 1.77 D, the mean axial length by IOLMaster was 24.6 +/- 1.1 mm, and subjects
      were 1.7 +/- 4.0 Delta exophoric. Refractive error was associated with the number
      of myopic parents (F = 3.83, p = 0.023), and the number of myopic parents was
      associated with the age of myopia onset (chi2 = 13.78, p = 0.001). In a
      multivariate analysis, onset of myopia (early vs. late) still had a significant
      effect on degree of myopia (F = 115.1, p < 0.001), but the number of myopic
      parents was no longer significant (F = 0.65, p = 0.52). For the ESM, the most
      frequently reported visual task was computer use (mean, 18.9%; range, 0-60.0%)
      and, overall, subjects reported near work activity 34.1% of the time (range, 0
      67.3%). CONCLUSIONS: The design of SPAN and the baseline characteristics of the
      cohort have been described. Parental history of myopia is related to the degree
      of myopia at baseline, but this effect is mediated by the age of onset of myopia.

PMID- 16909087
TI  - Visual performance of subjects wearing presbyopic contact lenses.
AB  - PURPOSE: The purpose of this study is to assess the visual performance of
      subjects wearing gas-permeable (GP) multifocal contact lenses, soft bifocal
      contact lenses, GP monovision lenses and spectacles. METHODS: The study included
      32 subjects between the ages of 42 and 65 years wearing GP monovision, the Acuvue
      Bifocal (Vistakon), the Essentials GP Multifocal (Blanchard), and progressive
      addition lenses (PAL; spectacles group). There were eight subjects in each of
      these groups who were already wearing these modalities. Binocular low (18%) and
      high (95%) contrast acuities were recorded using the Bailey-Lovie chart;
      binocular contrast sensitivity from 1.5 to 18 cycles per degree (cpd) measured
      with the Vistech VCTS 6500 system, and monocular glare sensitivity at three
      luminance settings (400, 100, and 12 foot lamberts) was measured using the
      brightness acuity tester (BAT). Binocular near visual task performance (a
      modified version of letter counting method used in previous presbyopic studies)
      was also assessed. RESULTS: For the contact lens-wearing groups, subjects wearing
      GP multifocals provided the best binocular high and low contrast acuity followed
      by soft bifocal wearers. There was relative parity between the binocular high and
      low contrast acuity with PAL and GP multifocal wearers. Monovision acuity,
      measured binocularly, was determined to be lower than the other three groups with
      this difference being most significant with high contrast acuity. Among contact
      lens-wearing groups, it was observed that GP multifocal lens wearers experienced
      the lowest amount of monocular disability glare followed by soft bifocal wearers
      and monovision wearers. Subjects wearing soft bifocal lenses and monovision
      demonstrated slightly reduced binocular contrast sensitivity at all spatial
      frequencies. In the contact lens groups, GP multifocal lens wearers had the
      highest binocular contrast sensitivity at all spatial frequencies, on parity with
      PAL wearers, except at the highest spatial frequency (18 cpd) at which PAL
      wearers had better vision. Error scores for the binocular near visual task
      performance between the four groups revealed subjects with GP multifocal lenses
      and PAL wearers to have the least errors, followed by monovision users and then
      soft bifocal wearers with the most errors. CONCLUSION: Subjects wearing GP
      multifocals, soft bifocals, monovision, and PAL spectacles have good binocular
      contrast sensitivity, satisfactory binocular low and high contrast acuity, and
      increased sensitivity to glare. Presbyopic subjects requiring the use of contact
      lenses under dim light levels could benefit from GP multifocal lenses. Contrast
      and glare sensitivity evaluations provide significant information regarding the
      visual performance of the presbyopic contact lenses and should be included in
      regular presbyopic contact lens fitting.

PMID- 16909088
TI  - Shooting a film photo slit lamp into the digital age.
AB  - PURPOSE: The purpose of this study is to describe a method of taking a slit lamp
      initially designed for film photography and updating it to provide digital
      photographs. METHODS: A "how-to" guide is provided. RESULTS: Updating a Nikon FS
      2 slit lamp is more economic than many practitioners may realize. By using what
      is already available on the market, a few steps can make a would-be dated
      instrument useful for many years to come. CONCLUSIONS: The upgrade to the Nikon
      FS-2 slit lamp is not only possible, but is able to functional well in the
      clinical setting and capture high-resolution photographs.

PMID- 16909089
TI  - Elective oophorectomy. Benefits, risks of removing ovaries.

PMID- 16909090
TI  - Kidney stone treatment linked to risks of diabetes, hypertension.

PMID- 16909091
TI  - Study finds taking estrogen alone doesn't increase breast cancer risk.

PMID- 16909092
TI  - Urinary incontinence. Taking charge of a common problem.

PMID- 16909093
TI  - Contact dermatitis. Allergens and irritants can affect skin.

PMID- 16909094
TI  - Mayo Clinic office visit. Patient safety. An interview with Prathibha Varkey,
      M.D., M.P.H.

PMID- 16909095
TI  - Don't leave fitness behind. Staying active away from home.

PMID- 16909096
TI  - What are some tips for finding a good sports bra?

PMID- 16909097
TI  - I've been told I may have ovarian cancer and am to undergo surgery. Does it
      matter what type of surgeon I have?

PMID- 16909098
TI  - Are any cold medications safe for a person on high blood pressure medication?

PMID- 16909099
TI  - A genomic analysis of adult T-cell leukemia.
AB  - Adult T-cell leukemia (ATL) is an intractable malignancy of CD4+ T cells that is
      etiologically associated with infection by human T-cell leukemia virus-type I.
      Most individuals in the chronic stage of ATL eventually undergo progression to a
      highly aggressive acute stage. To clarify the mechanism responsible for this
      stage progression, we isolated CD4+ cells from individuals in the chronic (n=19)
      or acute (n=22) stages of ATL and subjected them to profiling of gene expression
      with DNA microarrays containing >44,000 probe sets. Changes in chromosome copy
      number were also examined for 24 cell specimens with the use of microarrays
      harboring approximately 50,000 probe sets. Stage-dependent changes in gene
      expression profile and chromosome copy number were apparent. Furthermore,
      expression of the gene for MET, a receptor tyrosine kinase for hepatocyte growth
      factor (HGF), was shown to be specific to the acute stage of ATL, and the plasma
      concentration of HGF was increased in individuals in either the acute or chronic
      stage. HGF induced proliferation of a MET-positive ATL cell line, and this effect
      was blocked by antibodies to HGF. The HGF-MET signaling pathway is thus a
      potential therapeutic target for ATL.

PMID- 16909100
TI  - v-Myb represses the transcription of Ets-2.
AB  - The v-Myb oncogene causes monoblastic leukemia and transforms only myelomonocytic
      cells in culture. The v-Myb protein is nuclear and binds to specific DNA
      sequences. To identify genes regulated by v-Myb, we utilized primary cells
      transformed by a retrovirus encoding a v-Myb-estrogen receptor (ER) fusion
      protein. The Ets-2 gene was not expressed in v-Myb-ER transformed cells in the
      presence of estradiol, but was expressed within 4 h after estradiol withdrawal.
      The expression of Ets-2 also increased dramatically following phorbol ester
      induced differentiation of the v-Myb-transformed BM2 cell line. Conversely, CRYP
      alpha, encoding a transmembrane tyrosine phosphatase, was expressed in the
      presence but not the absence of estradiol in v-Myb-ER transformed cells. CRYP
      alpha was downregulated during the phorbol ester-induced differentiation of BM2
      cells. Although LIM-3 expression was estradiol-inducible in v-Myb-ER transformed
      monoblasts, LIM-3 was expressed neither in primary yolk sac cells transformed by
      unfused v-Myb nor in BM2 cells. We conclude that although v-Myb has been
      intensively studied as a transcriptional activator, v-Myb can repress
      biologically relevant genes such as Ets-2, which promotes macrophage
      differentiation. In addition, we have shown that some genes that are regulated by
      a v-Myb-ER fusion protein may not be relevant to the biological function of the
      unfused v-Myb protein.

PMID- 16909101
TI  - Promoter CpG hypermethylation and downregulation of XAF1 expression in human
      urogenital malignancies: implication for attenuated p53 response to apoptotic
      stresses.
AB  - XIAP-associated factor 1 (XAF1) is a new candidate tumor suppressor, which has
      been known to exert proapoptotic effects by interfering with the caspase
      inhibiting activity of XIAP. To explore the XAF1's candidacy for a suppressor in
      urogenital tumorigenesis, we investigated the XAF1 status in a series of cancer
      cell lines and primary tumors derived from the bladder, kidney and prostate.
      Expression of XAF1 transcript was undetectable or extremely low in 60% (3/5) of
      bladder, 66% (10/15) of kidney, and 100% (3/3) prostate cancer cell lines.
      Abnormal reduction of XAF1 was also found in 33% (18/55) of primary bladder and
      40% (8/20) of primary kidney tumors, and showed a correlation with advanced stage
      and high grade of bladder tumor. Hypermethylation at 14 CpG sites in the 5'
      proximal region of the XAF1 promoter was highly prevalent in cancers versus
      adjacent normal or benign tissues and tightly associated with reduced gene
      expression. XAF1 expression enhanced the apoptotic response of tumor cells to
      chemotherapeutic agents, such as etoposide or 5-FU. While XAF1 expression did not
      influence the subcellular distribution or expression of XIAP, it elevated the
      protein stability of p53 and its target gene expression. Moreover, the apoptosis
      sensitizing and growth suppression function of XAF1 was markedly impeded by
      blockade of p53 function. Collectively, our study demonstrates that epigenetic
      alteration of XAF1 is frequent in human urogenital cancers and may contribute to
      the malignant progression of tumors by rendering tumor cells a survival advantage
      partially through the attenuated p53 response to apoptotic stresses.

PMID- 16909102
TI  - Silencing of stathmin induces tumor-suppressor function in breast cancer cell
      lines harboring mutant p53.
AB  - Cancers harboring dominant-negative p53 mutations are often aggressive and
      difficult to treat. Direct attempts to restore wild-type p53 function have
      produced little clinical benefit. We investigated whether targeting a p53-target
      gene could induce certain tumor-suppressor characteristics. We found that
      inhibition of stathmin, a microtubule regulator that can be transcriptionally
      repressed by wild-type p53, restored certain wild-type functions to cancer cells
      with mutant p53. Silencing of stathmin by small interfering RNA (siRNA) in mutant
      p53 cell lines lowered expression to that observed following activation of wild
      type p53 by DNA damage in wild-type p53 cell lines. siRNA-induced repression of
      stathmin decreased cell proliferation, viability and clonogenicity in mutant p53
      cell lines. Furthermore, knockdown of stathmin partially restored cell-cycle
      regulation and activation of apoptosis. Therefore, targeting stathmin, a gene
      product that is overexpressed in the presence of mutant p53, may represent a
      novel approach to treating cancers with aberrant p53 function.

PMID- 16909103
TI  - ATR-dependent radiation-induced gamma H2AX foci in bystander primary human
      astrocytes and glioma cells.
AB  - Radiotherapy is an important treatment for patients suffering from high-grade
      malignant gliomas. Non-targeted (bystander) effects may influence these cells'
      response to radiation and the investigation of these effects may therefore
      provide new insights into mechanisms of radiosensitivity and responses to
      radiotherapy as well as define new targets for therapeutic approaches. Normal
      primary human astrocytes (NHA) and T98G glioma cells were irradiated with helium
      ions using the Gray Cancer Institute microbeam facility targeting individual
      cells. Irradiated NHA and T98G glioma cells generated signals that induced
      gammaH2AX foci in neighbouring non-targeted bystander cells up to 48 h after
      irradiation. gammaH2AX bystander foci were also observed in co-cultures targeting
      either NHA or T98G cells and in medium transfer experiments. Dimethyl sulphoxide,
      Filipin and anti-transforming growth factor (TGF)-beta 1 could suppress gammaH2AX
      foci in bystander cells, confirming that reactive oxygen species (ROS) and
      membrane-mediated signals are involved in the bystander signalling pathways.
      Also, TGF-beta 1 induced gammaH2AX in an ROS-dependent manner similar to
      bystander foci. ROS and membrane signalling-dependent differences in bystander
      foci induction between T98G glioma cells and normal human astrocytes have been
      observed. Inhibition of ataxia telangiectasia mutated (ATM) protein and DNA-PK
      could not suppress the induction of bystander gammaH2AX foci whereas the mutation
      of ATM- and rad3-related (ATR) abrogated bystander foci induction. Furthermore,
      ATR-dependent bystander foci induction was restricted to S-phase cells. These
      observations may provide additional therapeutic targets for the exploitation of
      the bystander effect.

PMID- 16909104
TI  - Constitutively active CCK2 receptor splice variant increases Src-dependent HIF-1
      alpha expression and tumor growth.
AB  - Gastrointestinal (GI) cancers ectopically express multiple splice variants of the
      cholecystokinin-2 (CCK(2))/gastrin receptor; however, their relative
      contributions to the cancer phenotype are unknown. The aim of this study was to
      compare the effects of CCK(2) receptor (CCK(2)R) and CCK(2i4sv)R expression on
      cell growth both in vitro and in vivo using a human epithelial cell model,
      HEK239. In vitro, receptor variant expression did not affect cell proliferation
      either in the absence or presence of agonist. However, in vivo, the expression of
      CCK(2i4sv)R, but not CCK(2)R, increases HEK293 tumor growth in a constitutive,
      Src-dependent manner. Enhanced tumorigenicity of CCK(2i4sv)R is associated with
      an Src-dependent increase in the transcription factor, hypoxia-inducible factor
      1alpha, its downstream target, vascular endothelial growth factor and tumor micro
      vessel density, suggesting that CCK(2i4sv)R may contribute to the growth and
      spread of GI cancers through agonist-independent mechanisms that enhance tumor
      angiogenesis.

PMID- 16909105
TI  - Frequent requirement of hedgehog signaling in non-small cell lung carcinoma.
AB  - Although it had previously been suggested that the hedgehog (HH) pathway might be
      activated in some lung tumors, the dependence of non-small cell lung carcinomas
      (NSCLC) for HH activity had not been comprehensively studied. During a screen of
      a panel of 60 human tumor cell lines with an HH antagonist, we observed that the
      proliferation of a subset of NSCLC cell lines was inhibited. These NSCLC cell
      lines express HH, as well as key HH target genes, consistent with them being
      activated through an autocrine mechanism. Interestingly, we also identified a
      number of NSCLC cell lines that express high levels of the downstream
      transcription factor GLI1 and harbor enhanced levels of HH activity, but appear
      insensitive to known HH antagonists. We hypothesized that the high levels of GLI1
      in these cells would function downstream of the HH antagonist target, allowing
      them to bypass the antagonist-mediated block in proliferation. Consistent with
      this hypothesis, when the levels of GLI1 are knocked down in such cells, they
      become sensitive to these inhibitors. We go on to show that a large percentage of
      primary NSCLC samples express GLI1, consistent with constitutive activation of
      the HH pathway in these samples. Taken together, these results establish the
      involvement of the HH signaling pathway in a subset of NSCLCs.

PMID- 16909106
TI  - PRIMA-1(MET) induces nucleolar accumulation of mutant p53 and PML nuclear body
      associated proteins.
AB  - We have previously identified PRIMA-1, a low molecular weight compound that
      restores the transcriptional transactivation function to mutant p53 and induction
      of apoptosis. To explore the molecular mechanism for PRIMA-1-induced mutant p53
      dependent apoptosis, we examined the intracellular distribution of mutant p53
      upon treatment with PRIMA-1(MET) by immunofluorescence staining. We found that
      PRIMA-1(MET) induced nucleolar translocation of mutant p53 and the promyelocytic
      leukemia (PML) nuclear body-associated proteins PML, CBP and Hsp70. Levels of
      Hsp70 were significantly enhanced by PRIMA-1(MET) treatment. PRIMA-Dead, a
      compound structurally related to PRIMA-1 but unable to induce mutant p53
      dependent apoptosis, failed to induce nucleolar translocation of mutant p53. Our
      results suggest that redistribution of mutant p53 to nucleoli plays a role in
      PRIMA-1-induced apoptosis.

PMID- 16909107
TI  - SIRT2, a tubulin deacetylase, acts to block the entry to chromosome condensation
      in response to mitotic stress.
AB  - We previously identified SIRT2, an nicotinamide adenine dinucleotide (NAD)
      dependent tubulin deacetylase, as a protein downregulated in gliomas and glioma
      cell lines, which are characterized by aneuploidy. Other studies reported SIRT2
      to be involved in mitotic progression in the normal cell cycle. We herein
      investigated whether SIRT2 functions in the mitotic checkpoint in response to
      mitotic stress caused by microtubule poisons. By monitoring chromosome
      condensation, the exogenously expressed SIRT2 was found to block the entry to
      chromosome condensation and subsequent hyperploid cell formation in glioma cell
      lines with a persistence of the cyclin B/cdc2 activity in response to mitotic
      stress. SIRT2 is thus a novel mitotic checkpoint protein that functions in the
      early metaphase to prevent chromosomal instability (CIN), characteristics
      previously reported for the CHFR protein. We further found that histone
      deacetylation, but not the aberrant DNA methylation of SIRT2 5'untranslated
      region is involved in the downregulation of SIRT2. Although SIRT2 is normally
      exclusively located in the cytoplasm, the rapid accumulation of SIRT2 in the
      nucleus was observed after treatment with a nuclear export inhibitor, leptomycin
      B and ionizing radiation in normal human fibroblasts, suggesting that nucleo
      cytoplasmic shuttling regulates the SIRT2 function. Collectively, our results
      suggest that the further study of SIRT2 may thus provide new insights into the
      relationships among CIN, epigenetic regulation and tumorigenesis.

PMID- 16909108
TI  - Bombesin induces cyclooxygenase-2 expression through the activation of the
      nuclear factor of activated T cells and enhances cell migration in Caco-2 colon
      carcinoma cells.
AB  - Cyclooxygenase-2 (Cox-2), the gastrin-release peptide (GRP) and its cognate
      receptor (GRP-R) are overexpressed in a significant percentage of colorectal
      carcinomas and are associated with cell growth, invasiveness and tumor
      progression. However, a molecular link between all of them in adenocarcinomas has
      not been established. Here, we show that bombesin (BBS), a GRP homolog,
      stimulates the expression of Cox-2 mRNA and protein in human colon adenocarcinoma
      Caco-2 cells, resulting in enhanced release of prostaglandin E(2). These effects
      were markedly inhibited by the specific BBS antagonist RC-3940-II. BBS promotes
      the activation of the nuclear factor of activated T cells (NFAT) through a
      Ca(2+)/calcineurin (Cn)-linked pathway. Upon BBS stimulation, the NFATc1 isoform
      translocates into the nucleus with a concomitant increase in NFATc1 binding to
      two specific recognition sites in the promoter region of the Cox-2 gene.
      Furthermore, inhibition of Cn activity by the immunosuppressive drug cyclosporin
      A impaired NFAT activation and diminished Cox-2 expression in BBS-stimulated
      cells. Interestingly, BBS pretreatment strongly enhances the invasive capacity of
      carcinoma cells, effect which was inhibited by a Cox-2-specific inhibitor. These
      findings provide the first evidence for the involvement of the Ca(2+)/Cn/NFAT
      pathway in BBS-mediated induction of genes involved in colon carcinoma
      invasiveness such as Cox-2.

PMID- 16909109
TI  - Src kinase phosphorylates vascular endothelial-cadherin in response to vascular
      endothelial growth factor: identification of tyrosine 685 as the unique target
      site.
AB  - Src-family tyrosine kinases are regulatory proteins that play a pivotal role in
      the disorganization of cadherin-dependent cell-cell contacts. We previously
      showed that Src was associated with vascular endothelial (VE)-cadherin and that
      tyrosine phosphorylation level of VE-cadherin was dramatically increased in
      angiogenic tissues as compared to quiescent tissues. Here, we examined whether VE
      cadherin was a direct substrate for Src in vascular endothelial growth factor
      (VEGF)-induced VE-cadherin phosphorylation, and we identified the target tyrosine
      sites. Co-transfections of Chinese hamster ovary cells (CHO) cells with VE
      cadherin and constitutively active Src (Y530F) resulted in a robust tyrosine
      phosphorylation of VE-cadherin that was not detected with kinase-dead Src
      (K298M). In an in vitro Src assay, the VE-cadherin cytoplasmic domain is directly
      phosphorylated by purified Src as well as the tyrosine residue 685 (Tyr)685
      containing peptide RPSLY(685)AQVQ. VE-cadherin peptide mapping from human
      umbilical vein endothelial cells stimulated by VEGF and VE-cadherin-CHO cells
      transfected with active Src revealed that Y685 was the unique phosphorylated
      site. The presence of PhosphoY685 was confirmed by its ability to bind to C
      terminal Src kinase-SH2 domain in a pull-down assay. Finally, we found that in a
      VEGF-induced wound-healing assay, cadherin adhesive activity was impaired by Src
      kinase inhibitors. These data identify that VEGF-induced-VE-cadherin tyrosine
      phosphorylation is mediated by Src on Y685, a process that appears to be critical
      for VEGF-induced endothelial cell migration.

PMID- 16909110
TI  - Role of E2F3 expression in modulating cellular proliferation rate in human
      bladder and prostate cancer cells.
AB  - Amplification and overexpression of the E2F3 gene at 6p22 in human bladder cancer
      is associated with increased tumour stage, grade and proliferation index, and in
      prostate cancer E2F3 overexpression is linked to tumour aggressiveness. We first
      used small interfering RNA technology to confirm the potential importance of E2F3
      overexpression in bladder cancer development. Knockdown of E2F3 expression in
      bladder cells containing the 6p22 amplicon strongly reduced the extent of
      bromodeoxyuridine (BrdU) incorporation and the rate of cellular proliferation. In
      contrast, knockdown of CDKAL1/FLJ20342, another proposed oncogene, from this
      amplicon had no effect. Expression cDNA microarray analysis on bladder cancer
      cells following E2F3 knockdown was then used to identify genes regulated by E2F3,
      leading to the identification of known E2F3 targets such as Cyclin A and CDC2 and
      novel targets including pituitary tumour transforming gene 1, Polo-like kinase 1
      (PLK1) and Caveolin-2. For both bladder and prostate cancer, we have proposed
      that E2F3 protein overexpression may cooperate with removal of the E2F inhibitor
      retinoblastoma tumor suppressor protein (pRB) to drive cellular proliferation. In
      support of this model, we found that ectopic expression of E2F3a enhanced the
      BrdU incorporation, a marker of cellular proliferation rate, of prostate cancer
      DU145 cells, which lack pRB, but had no effect on the proliferation rate of PC3
      prostate cancer cells that express wild-type pRB. BrdU incorporation in PC3 cells
      could, however, be increased by overexpressing E2F3a in cells depleted of pRB.
      When taken together, these observations indicate that E2F3 levels have a critical
      role in modifying cellular proliferation rate in human bladder and prostate
      cancer.

PMID- 16909111
TI  - FMIP controls the adipocyte lineage commitment of C2C12 cells by downmodulation
      of C/EBP alpha.
AB  - Fms interacting protein (FMIP) is a substrate for Fms tyrosine kinase, and a
      nuclear/cytoplasm shuttling protein with a leucine zipper. As the phosphorylation
      of FMIP is observed in insulin-stimulated preadipocytes, we examined the role of
      FMIP in adipocyte differentiation, using the mesenchymal multipotent stem cells,
      C2C12 cells, that can differentiate into adipocytes, muscle cells and
      osteoblasts. Ectopic expression of FMIP in C2C12 impairs the adipocyte
      differentiation induced by treatment with insulin, dexamethasone and 3-isobutyl-1
      methylxanthine. These cells exhibit muscle phenotype with multinuclear
      morphology. Furthermore, knockdown of endogenous FMIP expression by small
      interfering RNA improves adipocytic lineage commitment of C2C12 cells, while
      impairing muscle differentiation. Upon stimulation with insulin, CCAAT/enhancer
      binding protein (C/EBP)beta, but not C/EBPalpha, is upregulated in cells
      expressing ectopic FMIP, whereas in FMIP knockdown cells, C/EBPalpha is
      constitutively expressed. Ectopic expression of C/EBPalpha counteracts the
      effects of FMIP, whereas C/EBPalpha knockdown partially mimics the effects of
      FMIP in this system. Northern blot analysis and reverse transcriptase-polymerase
      chain reaction study reveal that ectopic FMIP-expressing cells do not contain the
      polyadenylated C/EBPalpha mRNA, but contain the C/EBPalpha pre-mRNA, suggesting
      that FMIP plays a role in RNA processing and/or export. Indeed, a member of the
      THO complex that plays a role in mRNA export, THOC1, is co-precipitated with
      FMIP. The data we have acquired on FMIP suggest that it is a target for tyrosine
      kinase receptors that potentiate mRNA export.

PMID- 16909112
TI  - Upregulation of two BH3-only proteins, Bmf and Bim, during TGF beta-induced
      apoptosis.
AB  - Transforming growth factor-beta (TGFbeta)-activated signalling pathways can lead
      to apoptosis, growth arrest or promotion of malignant behaviour, dependent on
      cellular context. The molecular mechanisms involved in TGFbeta-induced apoptosis
      remain controversial; although changes in gene expression are thought to be
      pivotal to the process, several different candidate apoptotic initiators and
      mediators have been proposed. Smad4, a critical component of the TGFbeta-induced
      transcriptional machinery, is shown here to be essential for induction of
      apoptosis. Gene expression analysis identified the proapoptotic Bcl-2 family
      members, Bmf and Bim, as induced by TGFbeta, dependent on both Smad4 and p38
      function and the generation of reactive oxygen species. TGFbeta-induced Bmf and
      Bim localize to cellular membranes implicated in apoptosis. Inhibition of the
      TGFbeta-induced expression of both these proteins together provides significant
      protection of cells from apoptosis. The TGFbeta-triggered cell death programme
      thus involves induction of multiple BH3-only proteins during the induction of
      apoptosis.

PMID- 16909113
TI  - Frequent loss of chromosome 9, homozygous CDKN2A/p14(ARF)/CDKN2B deletion and low
      TSC1 mRNA expression in pleomorphic xanthoastrocytomas.
AB  - The molecular pathogenesis of pleomorphic xanthoastrocytoma (PXA), a rare
      astrocytic brain tumor with a relatively favorable prognosis, is still poorly
      understood. We characterized 50 PXAs by comparative genomic hybridization (CGH)
      and found the most common imbalance to be loss on chromosome 9 in 50% of tumors.
      Other recurrent losses affected chromosomes 17 (10%), 8, 18, 22 (4% each).
      Recurrent gains were identified on chromosomes X (16%), 7, 9q, 20 (8% each), 4,
      5, 19 (4% each). Two tumors demonstrated amplifications mapping to 2p23-p25,
      4p15, 12q13, 12q21, 21q21 and 21q22. Analysis of 10 PXAs with available high
      molecular weight DNA by high-resolution array-based CGH indicated homozygous
      9p21.3 deletions involving the CDKN2A/p14(ARF)/CDKN2B loci in six tumors (60%).
      Interphase fluorescence in situ hybridization to tissue sections confirmed the
      presence of tumor cells with homozygous 9p21.3 deletions. Mutational analysis of
      candidate genes on 9q, PTCH and TSC1, revealed no mutations in PXAs with 9q loss
      and no evidence of TSC1 promoter methylation. However, PXAs consistently showed
      low TSC1 transcript levels. Taken together, our study identifies loss of
      chromosome 9 as the most common chromosomal imbalance in PXAs and suggests
      important roles for homozygous CDKN2A/p14(ARF)/CDKN2B deletion as well as low
      TSC1 mRNA expression in these tumors.

PMID- 16909114
TI  - Oncogenic transformation by the jaagsiekte sheep retrovirus envelope protein.
AB  - Retroviruses have played profound roles in our understanding of the genetic and
      molecular basis of cancer. Jaagsiekte sheep retrovirus (JSRV) is a simple
      retrovirus that causes contagious lung tumors in sheep, known as ovine pulmonary
      adenocarcinoma (OPA). Intriguingly, OPA resembles pulmonary adenocarcinoma in
      humans, and may provide a model for this frequent human cancer. Distinct from the
      classical mechanisms of retroviral oncogenesis by insertional activation of or
      virus capture of host oncogenes, the native envelope (Env) structural protein of
      JSRV is itself the active oncogene. A major pathway for Env transformation
      involves interaction of the Env cytoplasmic tail with as yet unidentified
      cellular adaptor(s), leading to the activation of PI3K/Akt and MAPK signaling
      cascades. Another potential mechanism involves the cell-entry receptor for JSRV,
      Hyaluronidase 2 (Hyal2), and the RON receptor tyrosine kinase, but the exact
      roles of these proteins in JSRV Env transformation remain to be better
      understood. Recently, a mouse model of lung cancer induced by JSRV Env has been
      developed, and the tumors in mice resemble those seen in sheep infected with JSRV
      and in humans. In this review, we summarize recent progress in our understanding
      the molecular mechanisms of oncogenic transformation by JSRV Env protein, and
      discuss the relevance to human lung cancer.

PMID- 16909115
TI  - Crk-associated substrate lymphocyte type regulates transforming growth factor
      beta signaling by inhibiting Smad6 and Smad7.
AB  - Crk-associated substrate lymphocyte type (Cas-L) is a 105 kDa docking protein
      with diverse functional properties, including regulation of cell division,
      proliferation, migration and adhesion. Cas-L is also involved in beta1 integrin-
      or antigen receptor-mediated signaling in B and T cells. In the present study, we
      demonstrate that Cas-L potentiates transforming growth factor-beta (TGF-beta)
      signaling pathway by interacting with Smad6 and Smad7. Immunoprecipitation
      experiments reveal that single domain deletion of full-length Cas-L completely
      abolishes its docking function with Smad6 and Smad7, suggesting that the natural
      structure of Cas-L is necessary for its association with Smad6 and Smad7. On the
      other hand, both N-terminal and C-terminal deletion mutants of Smad6 and Smad7
      still retain their docking ability to Cas-L, suggesting that Smad6 and Smad7
      possess several binding motifs to Cas-L. Moreover, Cas-L interaction with Mad
      homology (MH)2 domain, but not with MH1 domain of Smad6 or Smad7, ameliorates TGF
      beta-induced signaling pathway. Finally, depletion of Cas-L by small-interfering
      RNA oligo attenuates TGF-beta-induced growth inhibition of Huh-7 cells, with a
      concomitant reduction in phosphorylation of Smad2 and Smad3. These results
      strongly suggest that Cas-L is a potential regulator of TGF-beta signaling
      pathway.

PMID- 16909116
TI  - Transcriptional networks of knockout cell lines identify functional specificities
      of H-Ras and N-Ras: significant involvement of N-Ras in biotic and defense
      responses.
AB  - We characterized differential gene expression profiles of fibroblast cell lines
      harboring single or double-homozygous null mutations in H-ras and N-ras. Whereas
      the expression level of the individual H-, N- and K-ras genes appeared unaffected
      by the presence or absence of the other ras loci, significant differences were
      observed between the expression profiles of cells missing N-ras and/or H-ras.
      Absence of N-ras produced much stronger effects than absence of H-ras over the
      profile of the cellular transcriptome. N-ras(-/-) and H-ras(-/-) fibroblasts
      displayed rather antagonistic expression profiles and the transcriptome of H-ras(
      /-) cells was significantly closer to that of wild-type fibroblasts than to that
      of N-ras(-/-) cells. Classifying all differentially expressed genes into
      functional categories suggested specific roles for H-Ras and N-Ras. It was
      particularly striking in N-ras(-/-) cells the upregulation of a remarkable number
      of immunity-related genes, as well as of several loci involved in apoptosis.
      Reverse-phase protein array assays demonstrated in the same N-ras(-/-) cells the
      overexpression and nuclear migration of tyrosine phosphorylated signal transducer
      and activator of transcription 1 (Stat1) which was concomitant with
      transcriptional activation mediated by interferon-stimulated response elements.
      Significantly enhanced numbers of apoptotic cells were also detected in cultures
      of N-ras(-/-) cells. Our data support the notion that different Ras isoforms play
      functionally distinct cellular roles and indicate that N-Ras is significantly
      involved in immune modulation/host defense and apoptotic responses.

PMID- 16909117
TI  - Loss of oncostatin M receptor beta in metastatic melanoma cells.
AB  - Oncostatin M (OSM) is an interleukin-6 (IL-6) type cytokine originally described
      by its capacity to inhibit melanoma proliferation in vitro. Here, the mechanisms
      involved in resistance to growth inhibition by OSM were analysed for the first
      time on a large panel of metastatic melanoma cell lines. OSM resistance did not
      strictly correlate with IL-6, interferon-gamma or tumor necrosis factor-alpha
      resistance. Rather, it correlated with a specific loss of the OSM receptor-beta
      (OSMRbeta) subunit, in conjunction with a lower level of histone acetylation in
      the OSMRbeta promoter region. Treatment of various OSM-resistant melanoma cells
      with the histone deacetylase inhibitor Trichostatin A increased activity and
      histone acetylation of the OSMRbeta promoter as well as expression of OSMRbeta
      mRNA and protein, allowing OSM to activate the signal transducer and activator of
      transcription 3 (STAT3) and to inhibit proliferation. Other defects associated
      with OSM resistance were identified at the level of OSMRbeta transcription or
      protein expression, as well as downstream of or parallel to STAT3 activation.
      Altogether, our results suggest a role for OSM in the prevention of melanoma
      progression and that metastatic melanoma cells could escape this growth control
      by the epigenetic silencing of OSMRbeta.

PMID- 16909118
TI  - Oncogenic tyrosine kinase NPM/ALK induces activation of the MEK/ERK signaling
      pathway independently of c-Raf.
AB  - The mechanisms of cell transformation mediated by the highly oncogenic, chimeric
      NPM/ALK tyrosine kinase remain only partially understood. Here we report that
      cell lines and native tissues derived from the NPM/ALK-expressing T-cell lymphoma
      (ALK+ TCL) display phosphorylation of the extracellular signal-regulated protein
      kinase (ERK) 1/2 complex. Transfection of BaF3 cells with NPM/ALK induces
      phosphorylation of EKR1/2 and of its direct activator mitogen-induced
      extracellular kinase (MEK) 1/2. Depletion of NPM/ALK by small interfering RNA
      (siRNA) or its inhibition by WHI-154 abrogates the MEK1/2 and ERK1/2
      phosphorylation. The NPM/ALK-induced MEK/ERK activation is independent of c-Raf
      as evidenced by the lack of MEK1/2 and ERK1/2 phosphorylation upon c-Raf
      inactivation by two different inhibitors, RI and ZM336372, and by its siRNA
      mediated depletion. In contrast, ERK1/2 activation is strictly MEK1/2 dependent
      as shown by suppression of the ERK1/2 phosphorylation by the MEK1/2 inhibitor
      U0126. The U0126-mediated inhibition of ERK1/2 activation impaired proliferation
      and viability of the ALK+ TCL cells and expression of antiapoptotic factor Bcl-xL
      and cell cycle-promoting CDK4 and phospho-RB. Finally, siRNA-mediated depletion
      of both ERK1 and ERK2 inhibited cell proliferation, whereas depletion of ERK 1
      (but not ERK2) markedly increased cell apoptosis. These findings identify MEK/ERK
      as a new signaling pathway activated by NPM/ALK and indicate that the pathway
      represents a novel therapeutic target in the ALK-induced malignancies.

PMID- 16909119
TI  - NF-kappaB-independent sensitization of glioblastoma cells for TRAIL-induced
      apoptosis by proteasome inhibition.
AB  - The transcription factor nuclear factor-kappaB (NF-kappaB) is a key regulator of
      stress-induced transcriptional activation and has been implicated in mediating
      primary or acquired apoptosis resistance in various cancers. In the present
      study, we therefore investigated the role of NF-kappaB in regulating apoptosis in
      malignant glioma, a prototypic tumor refractory to current treatment approaches.
      Here, we report that constitutive NF-kappaB DNA-binding activity was low or
      moderate in eight different glioblastoma cell lines compared to Hodgkin's
      lymphoma cells, known to harbor aberrant constitutive NF-kappaB activity.
      Specific inhibition of NF-kappaB by overexpression of inhibitor of kappaB
      (IkappaB)alpha superrepressor did not enhance spontaneous apoptosis of
      glioblastoma cells. Also, overexpression of IkappaBalpha superrepressor had no
      significant impact on apoptosis induced by two prototypic classes of apoptotic
      stimuli, that is, chemotherapeutic drugs or death-inducing ligands such as TNF
      related apoptosis inducing ligand (TRAIL), which are known to trigger NF-kappaB
      activation as part of a cellular stress response. Similarly, inhibition of NF
      kappaB by the proteasome inhibitor MG132 did not increase doxorubicin (Doxo)
      induced apoptosis of glioblastoma cells, although it prevented DNA binding of NF
      kappaB complexes in response to Doxo. Interestingly, proteasome inhibition
      significantly sensitized glioblastoma cells for TRAIL-induced apoptosis. These
      findings indicate that the characteristic antiapoptotic function of NF-kappaB
      reported for many cancers is not a primary feature of glioblastoma and thus,
      specific NF-kappaB inhibition may not be effective for chemosensitization of
      glioblastoma. Instead, proteasome inhibitors, which enhanced TRAIL-induced
      apoptosis in an NF-kappaB-independent manner, may open new perspectives to
      increase the efficacy of TRAIL-based regimens in glioblastoma, which warrants
      further investigation.

PMID- 16909120
TI  - Modulation of Nr-13 antideath activity by peptide aptamers.
AB  - Tumor cells are characterized by deregulated proliferation and resistance to
      proapoptotic stimuli. The Bcl-2 family of antiapoptotic proteins is overexpressed
      in a large number of chemoresistant tumors. Downregulation or inhibition of
      antiapoptotic proteins might result in the sensitization of cancer cells to
      chemotherapeutic agents. In the present study, we took advantage of the peptide
      aptamer strategy to target Nr-13, a Bcl-2 antiapoptotic protein involved in
      neoplastic transformation by the Rous sarcoma virus. We isolated peptide aptamers
      that behave as Nr-13 regulators, in vitro and in mammalian cells in culture. Some
      of these aptamers have potential proapoptotic activities. These data suggest that
      peptide aptamers targeting the Bcl-2 family of apoptosis inhibitors may be useful
      for the development of anticancer molecules.

PMID- 16909121
TI  - Overcoming the radioresistance of prostate cancer cells with a novel Bcl-2
      inhibitor.
AB  - Bcl-2 overexpression is an important mechanism underlying the aggressive behavior
      of prostate cancer cells and their resistance to radio- or chemotherapy. HA14-1,
      a recently discovered organic Bcl-2 inhibitor, potently induces apoptosis in
      various human cancer cells. Sequential exposure of radioresistant LNCaP (wild
      type (wt) p53), LNCaP/Bcl-2 (wt p53) and PC3 (mutant p53) prostate cancer cells
      to a minimally cytotoxic concentration of 10 microM HA14-1 for 1 h followed by 1
      6 Gy gamma radiation, resulted in a highly synergistic (combination index <1.0)
      induction of cell death as determined by an apoptosis assay at 72 h, and a
      clonogenicity assay at 12 days, after the initial treatment. The reverse
      treatment sequence did not cause a synergistic induction of cell death. When
      compared to individual treatments, cell death induced by the combined treatment
      was associated with dramatically increased reactive oxygen species (ROS)
      generation, c-Jun N-terminal kinase (JNK) activation, Bcl-2 phosphorylation,
      cytochrome c release, caspase-3 activation and DNA fragmentation. Exposure to
      either 200 microg/ml of the antioxidant alpha-tocopherol or 10 microM JNK
      inhibitor SP600125 before the combined treatment resulted in decreased activation
      of JNK and caspase-3 as well as decreased DNA fragmentation. However, treatment
      with the pancaspase inhibitor carbobenzoxyl-valyl-alanyl-aspartyl-[O-methyl]
      fluoromethylketone before the combined treatment inhibited apoptosis without
      affecting JNK activation, and this inhibitory effect was enhanced in the presence
      of alpha-tocopherol or SP600125. Taken together, our results indicate that HA14-1
      potently sensitizes radioresistant LNCaP and PC3 cells to gamma radiation,
      regardless of the status of p53. ROS and JNK are important early signals that
      trigger both caspase-dependent and -independent cell death pathways and
      contribute to the apoptotic synergy induced by the combined treatments.

PMID- 16909122
TI  - Transfer of chromosome 3 fragments suppresses tumorigenicity of an ovarian cancer
      cell line monoallelic for chromosome 3p.
AB  - Multiple chromosome 3p tumor suppressor genes (TSG) have been proposed in the
      pathogenesis of ovarian cancer based on complex patterns of 3p loss. To attain
      functional evidence in support of TSGs and identify candidate regions, we applied
      a chromosome transfer method involving cell fusions of the tumorigenic OV90 human
      ovarian cancer cell line, monoallelic for 3p and an irradiated mouse cell line
      containing a human chromosome 3 in order to derive OV90 hybrids containing normal
      3p fragments. The resulting hybrids showed complete or incomplete suppression of
      tumorigenicity in nude mouse xenograft assays, and varied in their ability to
      form colonies in soft agarose and three-dimensional spheroids in a manner
      consistent with alteration of their in vivo tumorigenic phenotypes. Expression
      microarray analysis identified a set of common differentially expressed genes,
      such as SPARC, DAB2 and VEGF, some of which have been shown implicated in ovarian
      cancer. Genotyping assays revealed that they harbored normal 3p fragments, some
      of which overlapped candidate TSG regions (3p25-p26, 3p24 and 3p14-pcen)
      identified previously in loss of heterozygosity analyses of ovarian cancers.
      However, only the 3p12-pcen region was acquired in common by all hybrids where
      expression microarray analysis identified differentially expressed genes. The
      correlation of 3p12-pcen transfer and tumor suppression with a concerted re
      programming of the cellular transcriptome suggest that the putative TSG may have
      affected key underlying events in ovarian cancer.

PMID- 16909123
TI  - Farnesyltransferase and geranylgeranyltransferase I inhibitors upregulate RhoB
      expression by HDAC1 dissociation, HAT association and histone acetylation of the
      RhoB promoter.
AB  - Recently, we have shown that RhoB suppresses EGFR-, ErbB2-, Ras- and Akt-mediated
      malignant transformation and metastasis. In this paper, we demonstrate that the
      novel antitumor agents farnesyltransferase inhibitors (FTIs) and
      geranylgeranyltransferase I inhibitors (GGTIs) upregulate RhoB expression in a
      wide spectrum of human cancer cells including those from pancreatic, breast,
      lung, colon, bladder and brain cancers. RhoB induction by FTI-277 and GGTI-298
      occurs at the transcriptional level and is blocked by actinomycin D. Reverse
      transcription-PCR experiments documented that the increase in RhoB protein levels
      is due to an increase in RhoB transcription. Furthermore, treatment with FTIs and
      GGTIs of cancer cells results in HDAC1 dissociation, HAT association and histone
      acetylation of the RhoB promoter. Thus, promoter acetylation is a novel mechanism
      by which RhoB expression levels are regulated following treatment with the
      anticancer agents FTIs and GGTIs.

PMID- 16909124
TI  - Compensation and specificity of function within the E2F family.
AB  - Functions encoded by single genes in lower organisms are often represented by
      multiple related genes in the mammalian genome. An example is the retinoblastoma
      and E2F families of proteins that regulate transcription during the cell cycle.
      Analysis of gene function using germline mutations is often confounded by
      overlapping function resulting in compensation. Indeed, in cells deleted of the
      E2F1 or E2F3 genes, there is an increase in the expression of the other family
      member. To avoid complications of compensatory effects, we have used small
      interfering RNAs that target individual E2F proteins to generate a temporary loss
      of E2F function. We find that both E2F1 and E2F3 are required for cells to enter
      the S phase from a quiescent state, whereas only E2F3 is necessary for the S
      phase in growing cells. We also find that the acute loss of E2F3 activity affects
      the expression of genes encoding DNA replication and mitotic activities, whereas
      loss of E2F1 affects a limited number of genes that are distinct from those
      regulated by E2F3. We conclude that the long-term loss of E2F activity does lead
      to compensation by other family members and that the analysis of acute loss of
      function reveals specific and distinct roles for these proteins.

PMID- 16909125
TI  - Downregulation of RUNX3 and TES by hypermethylation in glioblastoma.
AB  - Glioblastoma, the most aggressive and least treatable form of malignant glioma,
      is the most common human brain tumor. Although many regions of allelic loss occur
      in glioblastomas, relatively few tumor suppressor genes have been found mutated
      at such loci. To address the possibility that epigenetic alterations are an
      alternative means of glioblastoma gene inactivation, we coupled pharmacological
      manipulation of methylation with gene profiling to identify potential methylation
      regulated, tumor-related genes. Duplicates of three short-term cultured
      glioblastomas were exposed to 5 microM 5-aza-dC for 96 h followed by cRNA
      hybridization to an oligonucleotide microarray (Affymetrix U133A). We based
      candidate gene selection on bioinformatics, reverse transcription-polymerase
      chain reaction (RT-PCR), bisulfite sequencing, methylation-specific PCR and
      matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Two
      genes identified in this manner, RUNX3 and Testin (TES), were subsequently shown
      to harbor frequent tumor-specific epigenetic alterations in primary
      glioblastomas. This overall approach therefore provides a powerful means to
      identify candidate tumor-suppressor genes for subsequent evaluation and may lead
      to the identification of genes whose epigenetic dysregulation is integral to
      glioblastoma tumorigenesis.

PMID- 16909126
TI  - Reg I-knockout mice reveal its role in regulation of cell growth that is required
      in generation and maintenance of the villous structure of small intestine.
AB  - Reg I (regenerating gene product I) is a growth factor that plays a central role
      in the generation and regeneration of the gastric mucosal architecture. On the
      other hand, mouse Reg I mRNA is expressed at the highest levels in the small
      intestine among the gastrointestinal tissues. In the current study, with the aim
      to clarify the role of Reg I protein in the small intestine, the temporal and
      spatial pattern of Reg I expression and the phenotype of Reg I-knockout mice in
      the tissue were examined. In the wild-type mice, immunohistochemistry localized
      Reg I protein expression in absorptive cells located in the lower half of the
      intestinal villi. Reg I expression was undetectable until embryonic day 13 (E13),
      when the fetal intestine still lacks villous structure; however, it dramatically
      increased at E17 along with the formation and maturation of the fetal intestinal
      villi. In the small intestine of the adult Reg I-knockout mice, less densely
      packed, round-shaped aberrant morphology of the absorptive cells was observed
      light microscopically, and electron microscopical examination revealed a
      strikingly loose connection of these cells to the basement membrane.
      Antiproliferating cell nuclear antigen staining and anti-Ki67 staining
      demonstrated the marked decrease in the number of proliferating cells in the
      small intestinal mucosa of the knockout mice. The cell migration speed visualized
      by one shot labeling of 5-bromodeoxyuridine was significantly slower in the
      knockout mice. These phenotypes of Reg I-knockout mice emerged, in accordance
      with the temporal pattern of Reg I expression described above, from E17. Reg I
      was considered to be a regulator of cell growth that is required to generate and
      maintain the villous structure of the small intestine.

PMID- 16909127
TI  - E2A protein degradation by the ubiquitin-proteasome system is stage-dependent
      during muscle differentiation.
AB  - The E2A proteins are basic helix-loop-helix transcription factors that regulate
      proliferation and differentiation in many cell types. In muscle cells, the E2A
      proteins form heterodimers with muscle regulatory factors such as MyoD, which
      then bind to DNA and regulate the transcription of target genes essential for
      muscle differentiation. We now demonstrate that E2A proteins are primarily
      localized in the nucleus in both C2C12 myoblasts and myotubes, and are degraded
      by the ubiquitin proteasome system evidenced by stabilization following treatment
      with the proteasome inhibitor, MG132. During the differentiation from myoblast to
      myotube, the cellular abundance of E2A proteins is relatively unaltered, despite
      significant changes (each approximately 5-fold) in the relative rates of protein
      synthesis and protein degradation via the ubiquitin-proteasome system. The rate
      of ubiquitin-proteasome-mediated E2A protein degradation depends on the myogenic
      differentiation state (t 1/2 approximately 2 h in proliferating myoblasts versus
      t 1/2 > 10 h in differentiated myotubes), and is also associated with cell cycle
      in non-muscle cells. Our findings reveal an important role for both translational
      and post-translational regulatory mechanisms in mediating the complex program of
      muscle differentiation determined by the E2A proteins.

PMID- 16909128
TI  - Characterization of epithelial cell shedding from human small intestine.
AB  - Intestinal epithelial cells migrate from the base of the crypt to the villi where
      they are shed. However, little is known about the cell shedding process. We have
      studied the role of apoptosis and wound healing mechanisms in cell shedding from
      human small intestinal epithelium. A method preparing paraffin sections of human
      small intestine that preserves cell shedding was developed. A total of 14 417
      villus sections were studied. The relationship of cell shedding to leukocytes
      (CD45), macrophages (CD68) and blood vessels (CD34) were studied by
      immunohistochemistry. Apoptotic cells were identified using the M30 antibody
      against cleaved cytokeratin 18 and an antibody against cleaved caspase-3.
      Potential wound healing mechanisms were studied using antibodies against Zona
      Occludens-1 (ZO-1) and phosphorylated myosin light chains (MLCs). We found that
      5.3% of villus sections contained a shedding cell. An eosin-positive gap was
      often seen within the epithelial monolayer beneath shedding cells. Shedding was
      not associated with leukocytes, macrophages or blood vessels. Cells always
      underwent apoptosis during ejection from the monolayer. Apoptotic bodies were
      never seen in the monolayer but morphologically normal cells that were positive
      for M30 or cleaved caspase-3 were often seen. ZO-1 protein was usually (41/42)
      localized to the apical pole of cells neighboring a shedding event.
      Phosphorylated MLCs could be identified in 50% of shedding events. In conclusion,
      cell shedding is associated with apoptosis though it remains unclear whether
      apoptosis initiates shedding. It is also associated with phosphorylation of MLCs;
      a process associated previously with wound healing.

PMID- 16909129
TI  - Insulators: exploiting transcriptional and epigenetic mechanisms.
AB  - Insulators are DNA sequence elements that prevent inappropriate interactions
      between adjacent chromatin domains. One type of insulator establishes domains
      that separate enhancers and promoters to block their interaction, whereas a
      second type creates a barrier against the spread of heterochromatin. Recent
      studies have provided important advances in our understanding of the modes of
      action of both types of insulator. These new insights also suggest that the
      mechanisms of action of both enhancer blockers and barriers might not be unique
      to these types of element, but instead are adaptations of other gene-regulatory
      mechanisms.

PMID- 16909130
TI  - Sleep, ghrelin, leptin and changes in body weight during a 1-year moderate
      intensity physical activity intervention.
AB  - OBJECTIVE: To investigate cross-sectional and longitudinal relationships among
      exercise, sleep, ghrelin and leptin. METHODS: We randomly assigned 173 post
      menopausal sedentary overweight (body mass index >or=24.0 kg/m(2) and >33% body
      fat) women aged 50-75 years living in western Washington State to either a
      facility- and home-based moderate-intensity physical activity intervention or a
      stretching control group. Fasting plasma ghrelin, leptin, measured height, weight
      and self-reported sleep were assessed at baseline and 12 months. RESULTS: There
      were no consistent cross-sectional patterns between self-reported sleep measures
      and ghrelin or leptin at baseline. The weight loss differences between exercisers
      and stretchers were greater for those who slept less at follow-up than at
      baseline compared to those whose sleep duration did not change (-3.2 kg, 95%
      confidence interval (CI) -5.8, -0.5). Improvements in sleep quality were
      associated with significantly greater differences between exercisers and
      stretchers for ghrelin increases (improved vs same sleep quality: +115 pg/ml, 95%
      CI +25, +206) and leptin decreases (improved vs worsened sleep quality: -5.7
      ng/ml, 95% CI -9.5, -1.5). CONCLUSION: There was only limited evidence that
      changes in sleep duration or quality modified exercise-induced changes in weight,
      ghrelin or leptin. Moreover, the observed differences were not in the directions
      hypothesized. Future longitudinal studies including population-based samples
      using objective measures of sleep and long follow-up may help to clarify these
      relationships.

PMID- 16909131
TI  - Interleukin-2/interferon-alpha2a/13-retinoic acid-based chemoimmunotherapy in
      advanced renal cell carcinoma: results of a prospectively randomised trial of the
      German Cooperative Renal Carcinoma Chemoimmunotherapy Group (DGCIN).
AB  - We performed a prospectively randomised clinical trial to compare the efficacy of
      four subcutaneous interleukin-2-(sc-IL-2) and sc interferon-alpha2a (sc-IFN
      alpha2a)-based outpatient regimens in 379 patients with progressive metastatic
      renal cell carcinoma. Patients with lung metastases, an erythrocyte sedimentation
      rate < or =70 mm h(-1) and neutrophil counts < or =6000 microl(-1) (group I) were
      randomised to arm A: sc-IL-2, sc-IFN-alpha2a, peroral 13-cis-retinoic acid (po
      13cRA) (n=78), or arm B: arm A plus inhaled-IL-2 (n=65). All others (group II)
      were randomised to arm C: arm A plus intravenous 5-fluorouracil (iv-5-FU)
      (n=116), or arm D: arm A plus po-Capecitabine (n=120). Median overall survival
      (OS) was 22 months (arm A; 3-year OS: 29.7%) and 18 months (arm B; 3-year OS:
      29.2%) in group I, and 18 months (arm C; 3-year OS: 25.7%) and 16 months (arm D;
      3-year OS: 32.6%) in group II. There were no statistically significant
      differences in OS, progression-free survival, and objective response between arms
      A and B, and between arms C and D, respectively. Given the known therapeutic
      efficacy of sc-IL-2/sc-INF-alpha2a/po-13cRA-based outpatient
      chemoimmunotherapies, our results did not establish survival advantages in favour
      of po-Capecitabine vs iv-5-FU, and in favour of short-term inhaled-IL-2 in
      patients with advanced renal cell carcinoma receiving systemic cytokines.

PMID- 16909133
TI  - Genetic and epigenetic alterations on the short arm of chromosome 11 are involved
      in a majority of sporadic Wilms' tumours.
AB  - Wilms' tumour is one of the most common solid tumours of childhood. 11p13 (WT1
      locus) and 11p15.5 (WT2 locus) are known to have genetic or epigenetic
      aberrations in these tumours. In Wilms' tumours, mutation of the Wilms tumour 1
      (WT1) gene at the WT1 locus has been reported, and the WT2 locus, comprising the
      two independent imprinted domains IGF2/H19 and KIP2/LIT1, can undergo maternal
      deletion or alterations associated with imprinting. Although these alterations
      have been identified in many studies, it is still not clear how frequently
      combined genetic and epigenetic alterations of these loci are involved in Wilms'
      tumours or how these alterations occur. To answer both questions, we performed
      genetic and epigenetic analyses of these loci, together with an additional gene,
      CTNNB1, in 35 sporadic Wilms' tumours. Loss of heterozygosity of 11p15.5 and loss
      of imprinting of IGF2 were the most frequent genetic (29%) and epigenetic (40%)
      alterations in Wilms' tumours, respectively. In total, 83% of the tumours had at
      least one alteration at 11p15.5 and/or 11p13. One-third of the tumours had
      alterations at multiple loci. Our results suggest that chromosome 11p is not only
      genetically but also epigenetically critical for the majority of Wilms' tumours.

PMID- 16909132
TI  - Multicenter phase II trial of accelerated cisplatin and high-dose epirubicin
      followed by surgery or radiotherapy in patients with stage IIIa non-small-cell
      lung cancer with mediastinal lymph node involvement (N2-disease).
AB  - To assess the therapeutic activity of accelerated cisplatin and high-dose
      epirubicin with erythropoietin and G-CSF support as induction therapy for
      patients with stage IIIa-N2 non-small-cell lung cancer (NSCLC). Patients with
      stage IIIa-N2 NSCLC were enrolled in a phase II trial. They received cisplatin 60
      mg m(-2) and epirubicin 135 mg m(-2) every 2 weeks for three courses combined
      with erythropoietin and G-CSF. Depending on results of clinical response to
      induction therapy and restaging, patients were treated with surgery or
      radiotherapy. In total, 61 patients entered from March 2001 to April 2004. During
      169 courses of induction chemotherapy, National Cancer Institute of Canada (NCI
      C) grade III/IV leucocytopenia was reported in 35 courses (20.7%), NCI-C grade
      III/IV thrombocytopenia in 26 courses (15.4%) and NCI-C grade III/IV anaemia in
      six courses (3.6%). Main cause of cisplatin dose reduction was nephrotoxicity (12
      courses). Most patients received three courses. There were no chemotherapy
      related deaths. Three patients were not evaluable for clinical response. Twenty
      eight patients had a partial response (48.3%, 95% CI: 36-61.1%), 24 stable
      disease and six progressive disease. After induction therapy, 30 patients
      underwent surgery; complete resection was achieved in 19 procedures (31.1%).
      Radical radiotherapy was delivered to 25 patients (41%). Six patients were
      considered unfit for further treatment. Median survival for all patients was 18
      months. Response rate of accelerated cisplatin and high-dose epirubicin as
      induction chemotherapy for stage IIIa-N2 NSCLC patients is not different from
      more commonly used cisplatin-based regimen.

PMID- 16909134
TI  - PTCH mutations and deletions in patients with typical nevoid basal cell carcinoma
      syndrome and in patients with a suspected genetic predisposition to basal cell
      carcinoma: a French study.
AB  - The patched (PTCH) mutation rate in nevoid basal cell carcinoma syndrome (NBCCS)
      reported in various studies ranges from 40 to 80%. However, few studies have
      investigated the role of PTCH in clinical conditions suggesting an inherited
      predisposition to basal cell carcinoma (BCC), although it has been suggested that
      PTCH polymorphisms could predispose to multiple BCC (MBCC). In this study, we
      therefore performed an exhaustive analysis of PTCH (mutations detection and
      deletion analysis) in 17 patients with the full complement of criteria for NBCCS
      (14 sporadic and three familial cases), and in 48 patients suspected of having a
      genetic predisposition to BCC (MBCC and/or age at diagnosis < or =40 years and/or
      familial BCC). Eleven new germline alterations of the PTCH gene were
      characterised in 12 out of 17 patients harbouring the full complement of criteria
      for the syndrome (70%). These were frameshift mutations in five patients,
      nonsense mutations in five patients, a small inframe deletion in one patient, and
      a large germline deletion in another patient. Only one missense mutation (G774R)
      was found, and this was in a patient affected with MBCC, but without any other
      NBCCS criterion. We therefore suggest that patients harbouring the full
      complement of NBCCS criteria should as a priority be screened for PTCH mutations
      by sequencing, followed by a deletion analysis if no mutation is detected. In
      other clinical situations that suggest genetic predisposition to BCC, germline
      mutations of PTCH are not common.

PMID- 16909137
TI  - CagA-producing Helicobacter pylori and increased risk of gastric cancer: a nested
      case-control study in Korea.
AB  - In a nested-case control study of 100 cases of gastric cancer and 400 matched
      controls in relation to virulence factors of Helicobacter pylori in a Korean
      cohort, CagA seropositivity was significantly associated with a higher risk of
      gastric cancer among H. pylori-infected subjects (OR=3.57, 95% CI 1.05-12.14).

PMID- 16909136
TI  - NK105, a paclitaxel-incorporating micellar nanoparticle, is a more potent
      radiosensitising agent compared to free paclitaxel.
AB  - NK105 is a micellar nanoparticle formulation designed to enhance the delivery of
      paclitaxel (PTX) to solid tumours. It has been reported to exert antitumour
      activity in vivo and to have reduced neurotoxicity as compared to that of free
      PTX. The purpose of this study was to investigate the radiosensitising effect of
      NK105 in comparison with that of PTX. Lewis lung carcinoma (LLC)-bearing mice
      were administered a single intravenous (i.v.) injection of PTX or NK105; 24 h
      after the drug administration, a proportion of the mice received radiation to the
      tumour site or lung fields. Then, the antitumour activity and lung toxicity were
      evaluated. In one subset of mice, the tumours were excised and specimens were
      prepared for analysis of the cell cycle distribution by flow cytometry. Combined
      NK105 treatment with radiation yielded significant superior antitumour activity
      as compared to combined PTX treatment with radiation (P=0.0277). On the other
      hand, a histopathological study of lung sections revealed no significant
      difference in histopathological changes between mice treated with PTX and
      radiation and those treated with NK105 and radiation. Flow-cytometric analysis
      showed that NK105-treated LLC tumour cells showed more severe arrest at the G2/M
      phase as compared to PTX-treated tumour cells. The superior radiosensitising
      activity of NK105 was thus considered to be attributable to the more severe cell
      cycle arrest at the G2/M phase induced by NK105 as compared to that induced by
      free PTX. The present study results suggest that further clinical trials are
      warranted to determine the efficacy and feasibility of combined NK105 therapy
      with radiation.

PMID- 16909138
TI  - Optimal selection for BRCA1 and BRCA2 mutation testing using a combination of
      'easy to apply' probability models.
AB  - To establish an efficient, reliable and easy to apply risk assessment tool to
      select families with breast and/or ovarian cancer patients for BRCA mutation
      testing, using available probability models. In a retrospective study of 263
      families with breast and/or ovarian cancer patients, the utility of the Frank
      (Myriad), Gilpin (family history assessment tool) and Evans (Manchester) model
      was analysed, to select 49 BRCA mutation-positive families. For various cutoff
      levels and combinations, the sensitivity and specificity were calculated and
      compared. The best combinations were subsequently validated in additional sets of
      families. Comparable sensitivity and specificity were obtained with the Gilpin
      and Evans models. They appeared to be complementary to the Frank model. To obtain
      an optimal sensitivity, five 'additional criteria' were introduced that are
      specific for the selection of small or uninformative families. The optimal
      selection is made by the combination 'Frank >or=16% or Evans2 >or=12 or one of
      five additional criteria'. The efficiency of the selection of families for
      mutation testing of BRCA1 and BRCA2 can be optimised by using a combination of
      available easy to apply risk assessment models.

PMID- 16909139
TI  - How is place of death from cancer changing and what affects it? Analysis of
      cancer registration and service data.
AB  - We aimed to compare trends in place of cancer death with the growth of palliative
      care and nursing home services, and investigate demographic, disease-related and
      area influences on individual place of death, using registration data for 216404
      patients with breast, lung, colorectal and prostate cancer and aggregate data on
      services in South East England. Between 1985 and 1994 there was a trend away from
      hospital death (67-44%), to home (17-30%) and hospice death (8-20%). After 1995,
      this partly reversed. By 2002, hospital death rose to 47%, home death dropped to
      23%, hospice death remained stable and nursing home death rose from 3 to 8%.
      Numbers of palliative care services increased, but trends for hospice and nursing
      home deaths most clearly followed the beds available. Cancer diagnosis and
      treatment influenced individual place of death, but between 1998 and 2002, age
      and area of residence were associated with most variation. Older patients and
      those living in more deprived areas died more often in hospitals and less often
      at home. Despite more palliative care services the proportion of people dying at
      home has not increased. Variation by age, deprivation and area of residence is
      unlikely to reflect patient preference. More active surveillance and planning
      must support policies for choice in end of life care.

PMID- 16909140
TI  - A multicenter phase III trial comparing irinotecan-gemcitabine (IG) with
      gemcitabine (G) monotherapy as first-line treatment in patients with locally
      advanced or metastatic pancreatic cancer.
AB  - Our purpose was to determine the response rate and median and overall survival of
      gemcitabine as monotherapy versus gemcitabine plus irinotecan in advanced or
      metastatic pancreatic cancer. Patients with histologically or cytologically
      confirmed adenocarcinoma who were chemotherapy and radiotherapy naive were
      enrolled. Patients were centrally randomised at a one-to-one ratio to receive
      either gemcitabine monotherapy (900 mg m(-2) on days 1, 8 and 15 every 4 weeks
      (arm G), or gemcitabine (days 1 and 8) plus irinotecan (300 mg m(-2) on day 8)
      (arm IG), repeated every 3 weeks. The total number of cycles administered was 255
      in the IG arm and 245 in the G arm; the median number of cycles was 3. In all,
      145 patients (71 in arm IG and 74 in arm G) were enrolled; 60 and 70 patients
      from arms IG and G, respectively, were evaluable. A complete clinical response
      was achieved in three (4.3%) arm G patients; nine (15%) patients in arm IG and
      four (5.7%) in arm G achieved a partial response. The overall response rate was:
      arm IG 15% and arm G 10% (95% CI 5.96-24.04 and 95% CI 2.97-17.03, respectively;
      P=0.387). The median time to tumour progression was 2.8 months and 2.9 months and
      median survival time was 6.4 and 6.5 months for the IG and G arms, respectively.
      One-year survival was 24.3% for the IG arm and 21.8% for the G arm. No
      statistically significant difference was observed comparing gemcitabine
      monotherapy versus gemcitabine plus irinotecan in the treatment of advanced
      pancreatic cancer, with respect to overall and 1-year survival.

PMID- 16909141
TI  - The relation between socioeconomic and demographic factors and tumour stage in
      women diagnosed with breast cancer in Denmark, 1983-1999.
AB  - The authors investigated the association between socioeconomic position and stage
      of breast cancer at the time of diagnosis in a nationwide Danish study. All 28
      765 women with a primary invasive breast cancer diagnosed between 1983 and 1999
      were identified in a nationwide clinical database and information on
      socioeconomic variables was obtained from Statistics Denmark. The risk of being
      diagnosed with a high-risk breast cancer, that is size >20 mm, lymph-node
      positive, ductal histology/high histologic grade and hormone receptor negative,
      was analysed by multivariate logistic regression. The adjusted odds ratio (OR)
      for high-risk breast cancer was reduced with longer education with a 12% reduced
      risk (95% confidence interval (CI), 0.80,0.96) in women with higher education and
      increased with reduced disposable income (low income group: OR, 1.22; 95% CI,
      1.10,1.34). There was an urban-rural gradient, with higher risk among rural women
      (OR 1.10; 95 % CI, 1.02, 1.18) and lower risk among women in the capital suburbs
      (OR, 0.85; 95% CI, 0.78, 0.93) and capital area (OR, 0.93; 95% CI, 0.84-1.02).
      These factors were significant only for postmenopausal women, although similar
      patterns were observed among the premenopausal women, suggesting a subgroup of
      aggressive premenopausal breast cancers less influenced by socioeconomic factors.

PMID- 16909142
TI  - Factors affecting the mesothelioma detection rate within national and
      international epidemiological studies: insights from Scottish linked cancer
      registry-mortality data.
AB  - ICD-9 code 163 (malignant neoplasm of pleura) listed as underlying cause of death
      detected only 40% of Scottish mesothelioma cases (all body sites) from the cancer
      registry in 1981-1999. This is lower than both the previously published 55%
      figure, derived from UK mesothelioma register data 1986-1991, which is based on
      any mention of mesothelioma on death certificates, cross-referenced to cancer
      registry data, and the 44% figure derived from Scottish mortality data 1981-1999,
      which captured any mention of mesothelioma on the death certificate. Detection
      from cancer registry data increased to 75% under ICD-10 in Scotland, confirming
      earlier predictions of the benefit of ICD-10's more specific mesothelioma codes.
      Including the accidental poisoning codes E866.4 (ICD-9) and X49 (ICD-10),
      covering poisoning by 'unspecified' and 'other' causes, which appear to have been
      used as coding surrogates for mesothelioma when asbestos exposure was explicitly
      mentioned in deaths suggestive of a mesothelioma, and which are recorded as the
      underlying cause of death in 4-7% of mesotheliomas, may improve the mesothelioma
      detection rate in future epidemiological studies.

PMID- 16909145
TI  - Should Codes of Ethics include expectations of others?

PMID- 16909147
TI  - Moral creativity in science and engineering.
AB  - Creativity in science and engineering has moral significance and deserves
      attention within professional ethics, in at least three areas. First, much
      scientific and technological creativity constitutes moral creativity because it
      generates moral benefits, is motivated by moral concern, and manifests virtues
      such as beneficence, courage, and perseverance. Second, creativity contributes to
      the meaning that scientists and engineers derive from their work, thereby
      connecting with virtues such as authenticity and also faults arising from
      Faustian trade-offs. Third, morally creative leadership is important at all
      levels of science and engineering.

PMID- 16909143
TI  - A multicenter international study on the Spinal Cord Independence Measure,
      version III: Rasch psychometric validation.
AB  - BACKGROUND: A third version of the Spinal Cord Independence Measure (SCIM III),
      made up of three subscales, was formulated following comments by experts from
      several countries and Rasch analysis performed on the previous version.
      OBJECTIVE: To examine the validity, reliability, and usefulness of SCIM III using
      Rasch analysis. DESIGN: Multicenter cohort study. SETTING: Thirteen spinal cord
      units in six countries from North America, Europe, and the Middle-East. SUBJECTS:
      425 patients with spinal cord lesions (SCL). INTERVENTIONS: SCIM III assessments
      by professional staff members. Rasch analysis of admission scores. MAIN OUTCOME
      MEASURES: SCIM III subscale match between the distribution of item difficulty
      grades and the patient ability measurements; reliability of patient ability
      measures; fit of data to Rasch model requirements; unidimensionality of each
      subscale; hierarchical ordering of categories within items; differential item
      functioning across classes of patients and across countries. RESULTS: Results
      supported the compatibility of the SCIM subscales with the stringent Rasch
      requirements. Average infit mean-square indices were 0.79-1.06; statistically
      distinct strata of abilities were 3 to 4; most thresholds between adjacent
      categories were properly ordered; item hierarchy was stable across most of the
      clinical subgroups and across countries. In a few items, however, misfit or
      category threshold disordering were found. CONCLUSIONS: The scores of each SCIM
      III subscale appear as a reliable and useful quantitative representation of a
      specific construct of independence after SCL. This justifies the use of SCIM in
      clinical research, including cross-cultural trials. The results also suggest that
      there is merit in further refining the scale.

PMID- 16909148
TI  - Social and ethical dimensions of nanoscale science and engineering research.
AB  - Continuing advances in human ability to manipulate matter at the atomic and
      molecular levels (i.e. nanoscale science and engineering) offer many previously
      unimagined possibilities for scientific discovery and technological development.
      Paralleling these advances in the various science and engineering sub-disciplines
      is the increasing realization that a number of associated social, ethical,
      environmental, economic and legal dimensions also need to be explored. An
      important component of such exploration entails the identification and analysis
      of the ways in which current and prospective researchers in these fields
      conceptualize these dimensions of their work. Within the context of a National
      Science Foundation funded Research Experiences for Undergraduates (REU) program
      in nanomaterials processing and characterization at the University of Central
      Florida (2002-2004), here I present for discussion (i) details of a
      "nanotechnology ethics" seminar series developed specifically for students
      participating in the program, and (ii) an analysis of students' and participating
      research faculty's perspectives concerning social and ethical issues associated
      with nanotechnology research. I conclude with a brief discussion of implications
      presented by these issues for general scientific literacy and public science
      education policy.

PMID- 16909149
TI  - Comparative analysis of the risk-handling procedures for gene technology
      applications in medical and plant science.
AB  - In this paper we analyse how the risks associated with research on transgenic
      plants are regulated in Sweden. The paper outlines the way in which pilot
      projects in the plant sciences are overseen in Sweden, and discusses the
      international and national background to the current regulatory system. The
      historical, and hitherto unexplored, reasons for the evolution of current
      administrative and legislative procedures in plant science are of particular
      interest. Specifically, we discuss similarities and differences in the regulation
      of medicine and plant science, and we examine the tendency towards dichotomizing
      risk--focusing on social/ethical risks in medicine and biological risks in plant
      science. The context of this article is the Synpraxia research project, an inter
      disciplinary program combining expertise in sciences and the humanities.

PMID- 16909150
TI  - Research misconduct among clinical trial staff.
AB  - Between 1993 and 2002, 39 clinical trial staff were investigated for scientific
      misconduct by the Office of Research Integrity (ORI). Analysis of ORI case
      records reveals practices regarding workload, training and supervision that
      enable misconduct. Considering the potential effects on human subjects
      protection, quality and reliability of data, and the trustworthiness of the
      clinical research enterprise, regulations or guidance on use of clinical trial
      staff ought to be available. Current ORI regulations do not hold investigators or
      institutions responsible for supervision and training of clinical trial staff.
      Given the important issues at stake, the definition of research misconduct should
      encompass the intentional or negligent mismanagement of scientific projects.
      Individual institutions and professional associations not only can but should
      adopt stricter standards of conduct than those reflected in federal regulations.

PMID- 16909151
TI  - Protecting the Navajo People through tribal regulation of research.
AB  - This essay explores the process and issues related to community collaborative
      research that involves Native Americans generally, and specifically examines the
      Navajo Nation's efforts to regulate research within its jurisdiction. Researchers
      need to account for both the experience of Native Americans and their own
      preconceptions about Native Americans when conducting research about Native
      Americans. The Navajo Nation institutionalized an approach to protecting members
      of the nation when it took over Institutional Review Board (IRB) responsibilities
      from the US Indian Health Service (IHS) in 1996. While written regulations for
      the Navajo Nation IRB are not dissimilar, and in some ways are less detailed than
      those of the IHS IRB, in practice the Navajo Nation allows less flexibility.
      Primary examples of this include not allowing expedited review and requiring
      prepublication review of all manuscripts. Because of its broad mandate, the
      Navajo Nation IRB may also require review of some projects that would not
      normally be subject to IRB approval, including investigative journalism and
      secondary research about Navajo People that does not involve direct data
      collection from human subjects.

PMID- 16909152
TI  - Self-governance, self-representation, self-determination and the questions of
      research ethics--commentary on "Protecting the Navajo People through tribal
      regulation of research".

PMID- 16909153
TI  - Research with groups: group rights, group consent, and collaborative research
      commentary on "Protecting the Navajo People through tribal regulation of
      research".

PMID- 16909154
TI  - Heidegger's resonance with engineering: the primacy of practice.
AB  - This paper describes how some aspects of Martin Heidegger's philosophy resonate
      strongly with an engineering outlook. He argued that practice was more
      "primordial"" than theory, though preserving an important role for theoretical
      understanding as well, thus speaking to the gap between engineering education
      (highly theoretical) and engineering practice (mostly empirical). He also
      underlined the reality of "average" practices into which we are socialized,
      though affirming the potential for original work and action too, thus providing
      the grounds for self-actualization whether within the routine or in transcending
      it. His notion of "thrownness" emphasizes the importance of context, with which
      engineers are constantly engaged. While all this relates to the idea of our
      "being", Heidegger also dealt with the influence of time on our practices. Future
      death could be seen as spurring innovation, cultural history as a source for
      critiquing current practice and the present "situation" as the immediate context
      for corrective action. His major book is appropriately called "Being and Time".

PMID- 16909155
TI  - Scientific misconduct and science ethics: a case study based approach.
AB  - The Schon misconduct case has been widely publicized in the media and has sparked
      intense discussions within and outside the scientific community about general
      issues of science ethics. This paper analyses the Report of the official
      Committee charged with the investigation in order to show that what at first
      seems to be a quite uncontroversial case, turns out to be an accumulation of many
      interesting and non-trivial questions (of both ethical and philosophical
      interest). In particular, the paper intends to show that daily scientific
      practices are structurally permeated by chronic problems; this has serious
      consequences for how practicing scientists assess their work in general, and
      scientific misconduct in particular. A philosophical approach is proposed that
      sees scientific method and scientific ethics as inextricably interwoven.
      Furthermore, the paper intends to show that the definition of co-authorship that
      the members of the Committee use, although perhaps clear in theory, proves highly
      problematic in practice and raises more questions that it answers. A final plea
      is made for a more self-reflecting attitude of scientists as far as the moral and
      methodological profile of science is concerned as a key element for improving not
      only their scientific achievements, but also their assessment of problematic
      cases.

PMID- 16909156
TI  - Duplicate publication and 'paper inflation' in the Fractals literature.
AB  - The similarity of documents in a large database of published Fractals articles
      was examined for redundancy. Three different text matching techniques were used
      on published Abstracts to identify redundancy candidates, and predictions were
      verified by reading full text versions of the redundancy candidate articles. A
      small fraction of the total articles in the database was judged to be redundant.
      This was viewed as a lower limit, because it excluded cases where the concepts
      remained the same, but the text was altered substantially. Far more pervasive
      than redundant publications were publications that did not violate the letter of
      redundancy but rather violated the spirit of redundancy. There appeared to be
      widespread publication maximization strategies. Studies that resulted in one
      comprehensive paper decades ago now result in multiple papers that focus on one
      major problem, but are differentiated by parameter ranges, or other stratifying
      variables. This 'paper inflation' is due in large part to the increasing use of
      metrics (publications, patents, citations, etc) to evaluate research performance,
      and the researchers' motivation to maximize the metrics.

PMID- 16909157
TI  - An analytic hierarchy process model to apportion co-author responsibility.
AB  - The analytic hierarchy process (AHP) can be used to determine co-author
      responsibility for a scientific paper describing collaborative research. The
      objective is to deter scientific fraud by holding co-authors accountable for
      their individual contributions. A hierarchical model of the research presented in
      a paper can be created by dividing it into primary and secondary elements. The co
      authors then determine the contributions of the primary and secondary elements to
      the work as a whole as well as their own individual contributions. They can use
      the results to determine authorship order.

PMID- 16909158
TI  - Commentary on "An analytical hierarchy process model to apportion co-author
      responsibility".

PMID- 16909159
TI  - Student perceptions of the effectiveness of education in the responsible conduct
      of research.
AB  - Responsible conduct of research (RCR) courses are widely taught, but little is
      known about the purposes or effectiveness of such courses. As one way to assess
      the purposes of these courses, students were surveyed about their perspectives
      after recent completion of one of eleven different research ethics courses at ten
      different institutions. Participants (undergraduate and graduate students, post
      doctoral fellows and faculty, staff and researchers) enrolled in RCR courses in
      spring and fall of 2003 received a voluntary, anonymous survey from their
      instructors at the completion of the course. Responses were received from 268
      participants. Seventy-seven percent of open-ended responses listed specific kinds
      of information learned; only a few respondents talked about changes in skills or
      attitudes. The perception that courses did more to provide information than to
      foster skills or attitudes was verified in quantitative responses (P<0.0001).
      Over 75% of the respondents specifically noted that courses were useful in
      preparing them to recognize, avoid, and respond to research misconduct. The two
      principal findings of this multi-institutional study are that respondents
      reported: (1) a wide variety of positive outcomes for research ethics courses,
      but that (2) the impact on knowledge was greater than that for changes in skills
      or attitudes.

PMID- 16909160
TI  - Practical three color live cell imaging by widefield microscopy.
AB  - Live cell fluorescence microscopy using fluorescent protein tags derived from
      jellyfish and coral species has been a successful tool to image proteins and
      dynamics in many species. Multi-colored aequorea fluorescent protein (AFP)
      derivatives allow investigators to observe multiple proteins simultaneously, but
      overlapping spectral properties sometimes require the use of sophisticated and
      expensive microscopes. Here, we show that the aequorea coerulescens fluorescent
      protein derivative, PS-CFP2 has excellent practical properties as a blue
      fluorophore that are distinct from green or red fluorescent proteins and can be
      imaged with standard filter sets on a widefield microscope. We also find that by
      widefield illumination in live cells, that PS-CFP2 is very photostable. When
      fused to proteins that form concentrated puncta in either the cytoplasm or
      nucleus, PSCFP2 fusions do not artifactually interact with other AFP fusion
      proteins, even at very high levels of over-expression. PSCFP2 is therefore a good
      blue fluorophore for distinct three color imaging along with eGFP and mRFP using
      a relatively simple and inexpensive microscope.

PMID- 16909162
TI  - Advantages of a unique DNA-based vaccine in comparison to paclitaxel in treatment
      of an established intracerebral breast cancer in mice.
AB  - In this study we compared the benefits of treating C3H/He mice with an
      established intracerebral breast carcinoma by immunization with a unique DNA
      based vaccine to chemotherapy with paclitaxel. Prior studies revealed the
      immunotherapeutic properties of a vaccine prepared by transfer of genomic DNA
      from breast cancer cells into a highly immunogenic cell line. Here, C3H/He mice
      with an established intracerebral breast cancer were treated either by injection
      into the tumor bed through a unique cannula system with the cell based vaccine or
      with paclitaxel administered intraperitoneally. Both treatment strategies were
      effective in prolonging survival and stimulating a systemic anti-tumor immune
      response (p< 0.025). However, unlike mice treated with the vaccine, the animals
      that received paclitaxel alone displayed significant toxic side effects. No
      additional therapeutic advantage was detected when these two treatment strategies
      were combined. The vaccine tended to provide a somewhat better therapeutic and
      clearly better systemic immunologic effect based on two independent spleen cell
      assays in comparison to paclitaxel.

PMID- 16909163
TI  - Stereoselective synthesis of the C(1)-C(13) segment of dolabelide B.
AB  - The efficient construction of the C(1)-C(13) segment of dolabelide B is
      described. A key element of the synthesis entails BITIP catalyzed asymmetric
      methallylation to establish the C(7) stereocenter, which was then used to direct
      the stereoselective installation of the C(9) and C(11) centers through Evans
      reduction and 1,5-anti aldol condensation, respectively.

PMID- 16909164
TI  - On Specifying Specificity: Facial Expressions at 4 Months.
AB  - Izard (2004/this issue) clarifies the position of differential emotions theory by
      proposing a distinction between hard and soft versions of event-emotion
      expression relations. We concur that the best design to examine situational
      specificity in facial expressions is one that utilizes multiple stimulus
      situations assessed over multiple occasions and ages. However, the problem of how
      to identify, a priori, a family of stimulus situations remains. We offer an
      example from our own recent work demonstrating how facial expressions and
      physiological indexes may converge to indicate the presence of a meaningful
      family of stimulus situations. Specifically, we found evidence for a family of
      frustrating, goal-blocking events that elicited expressions and cortisol
      responses indicative of anger at 4 months. Yet, individual differences exist in
      that these situations also elicited expressions and cortisol changes indicative
      of sadness. Identification of a more comprehensive set of such situations
      throughout infancy will allow researchers to more systematically examine the
      degree to which situational specificity of emotions is present.

PMID- 16909165
TI  - Predictors of Arab American Adolescent Tobacco Use.
AB  - This study examined personal, psychosocial, sociocultural, and environmental
      predictors in tobacco use for 1671 Arab American adolescents. Cigarette smoking
      in past 30 days was 6.9%. This increased from 1% at age 14 to 14% at age 18.
      Twenty-nine percent of the youths reported 'ever cigarette smoking.'
      Experimentation with narghile was 27%; it increased from 23% at 14 years to 40%
      at 18 years. All trends were significant (p < .001). Logistic regression analyses
      found ten predictors for 'smoked a cigarette in past 30 days' and nine and seven,
      respectively, for 'ever smoked a cigarette or narghile'. Friends and family
      members smoking were the strongest predictors of cigarette smoking and 'ever
      narghile use.' 'Ever narghile use' supported cigarette smoking.

PMID- 16909167
TI  - MESAB: 21 years of bursaries for black medics.

PMID- 16909166
TI  - The role of omalizumab in the treatment of severe allergic asthma.
AB  - BACKGROUND: A novel anti-immunoglobulin E (anti-IgE) therapy for asthma,
      omalizumab, has been approved for use in Canada. OBJECTIVE: To review the basic
      and clinical data for omalizumab, and to examine its possible role for asthma
      management in Canada. METHODS: A literature search from 1960 to 2006 was
      conducted in MEDLINE to identify studies of omalizumab. In addition, abstracts
      from recent respiratory and allergy scientific meetings were sought, and any
      unpublished data were requested from the manufacturer. A consensus panel of
      respiratory and allergy specialists reviewed and summarized the data, and derived
      a set of recommendations for omalizumab use. RESULTS: Omalizumab is a humanized
      monoclonal antibody designed to bind to the C epsilon 3 domain of the IgE
      molecule, forming soluble immune complexes that are cleared by the
      reticuloendothelial system. Subcutaneous injections, given at two- or four-week
      intervals at the recommended dose, result in a rapid decrease in free circulating
      IgE levels. In two phase III clinical trials of 1405 adult and adolescent
      patients with moderate to severe asthma maintained on moderate doses of inhaled
      corticosteroids (ICS), omalizumab reduced exacerbation rates compared with
      placebo, and was associated with improved symptoms and a greater corticosteroid
      sparing effect. In a trial of 419 patients with severe disease that was
      uncontrolled despite the use of high-dose ICS and concurrent long-acting beta2
      agonists, severe exacerbations were 50% less frequent in omalizumab-treated
      patients than in control subjects. Retrospective analyses have identified the
      characteristics of patients most likely to respond to omalizumab treatment.
      RECOMMENDATIONS: Omalizumab may be considered as a potential adjunctive therapy
      in atopic patients with severe asthma uncontrolled by conventional therapy with
      optimal doses of ICS and appropriate adjunctive therapy (eg, long-acting beta2
      agonists). Typically, patients are identified by the need for frequent short
      course or continuous oral corticosteroids. Therapy should be initiated only after
      review by a specialist to confirm the diagnosis and that conventional therapy is
      optimal.

PMID- 16909168
TI  - Cot death controversies.

PMID- 16909170
TI  - Triage in South African hospitals.

PMID- 16909169
TI  - Palliative care--attitudes and practices of Bloemfontein general practitioners
      and medical officers.

PMID- 16909171
TI  - Orthodontic management of achondroplasia.

PMID- 16909172
TI  - Characteristics of clients seeking first- and second-trimester terminations of
      pregnancy in public health facilities in Cape Town.

PMID- 16909173
TI  - Inspiring rural health--a fierce and distant light.

PMID- 16909174
TI  - Cycling doctor's breathtaking achievement.

PMID- 16909175
TI  - Ibogaine may help drug addicts live the 'never again'.

PMID- 16909176
TI  - Valkenberg's psychiatric care leaps forward a century.

PMID- 16909177
TI  - A case of dura mater graft-associated Creutzfeldt-Jakob disease in South Africa.

PMID- 16909178
TI  - Lodox Statscan proves to be invaluable in forensic medicine.

PMID- 16909179
TI  - Interaction between ketoconazole and domperidone and the risk of QT prolongation-
      important safety information.

PMID- 16909180
TI  - A case for the provision of positron emission tomography (PET) in South African
      public hospitals.

PMID- 16909181
TI  - Disseminated AIDS-associated Kaposi's sarcoma in pregnancy.

PMID- 16909182
TI  - Digital X-rays come of age.

PMID- 16909183
TI  - Short emergency department length of stay attributed to full-body digital
      radiography--a review of 3 paediatric cases.

PMID- 16909184
TI  - Profile of rape victims treated at the Tshepong Victim Support Centre, National
      District Hospital, Bloemfontein.

PMID- 16909185
TI  - Mucinous colonic adenocarcinoma in patients aged under 25 years.

PMID- 16909186
TI  - Combined condom and contraceptive use among South African women.

PMID- 16909187
TI  - Separation-survivability--the elusive moral cut-off point?
AB  - Act 92 of 1996, the Choice on Termination of Pregnancy Act, seeks to promote
      female autonomy. The Act makes no reference to the nature of the abortus-
      implying its moral insignificance. Utilitarian arguments on the value of life
      strongly support this position. Utilitarians argue that neither belonging to the
      human species, nor possession of the potential to develop into a person, is a
      significant intrinsic characteristic in determining the value of life. For them
      the entrance requirement to any conception of moral significance is sentience-
      the ability to suffer. Full moral significance is only accorded to 'persons'. A
      person is someone who has attained a sufficient level of self-awareness to have
      an interest in the continuance of its existence. This develops some time after
      birth. 'Conservatives' argue for conception as the moral cut-off point after
      which termination is morally unacceptable; 'liberals' hold that there is no such
      prenatal point. Both of these notions are problematic, as is the notion of
      sentience. We argue that separation-survivability is the only morally acceptable
      cut-off point, based on four premises, viz. (i) a particular notion of
      potentiality; (ii) the inextricable, mutual relationship between human beings and
      their world (without either, the other cannot exist); (iii) the moral
      correspondence of the viable fetus and the neonate; and (iv) the moral
      unacceptability of infanticide. We support a graded position on the value of
      prenatal human life, and a 'moderate' stance on termination--that notwithstanding
      possessing some moral significance, other arguments may trump this up to the
      point of separation-survivability. This seriously problematises 'partial birth'
      abortion, and the utilitarian argument on the value of life.

PMID- 16909188
TI  - Oral trimethoprim-sulphamethoxazole levels in stable HIV-infected children.
AB  - BACKGROUND: Effective treatment of Pneumocystis jiroveci pneumonia (PCP) requires
      therapeutic serum concentrations of 5-10 microg/ml trimethoprim (TMP);
      consequently intravenous trimethoprim-sulphamethoxazole (TMP-SMZ) is recommended
      therapy. However, oral therapy is desirable as the intravenous route is costly,
      time-consuming, more difficult to administer and carries a risk of needlestick
      injury. OBJECTIVE: To investigate whether therapeutic TMP levels for treatment of
      PCP can be attained with oral therapy in HIV-infected children. METHODS: A
      prospective dose-escalation study was undertaken of serum TMP levels attained
      following oral doses of TMP of 5 mg/kg, 10 mg/kg or 20 mg/kg in stable HIV
      infected children. Children who received a 20 mg/kg dose were randomised to get a
      second dose (5 or 10 mg/kg TMP) at 6 hours. TMP levels were measured at baseline,
      peak (3 hours), and trough (6 hours) using liquid chromatography. An additional
      TMP level was taken at 9 hours in those who received a second TMP dose. RESULTS:
      Median (25th-75th percentile) peak serum TMP levels following a 5 mg/kg, 10 mg/kg
      or 20 mg/kg oral loading dose were 0.93 (0.5-1.5) microg/ml, 1.94 (1.4-2.2)
      microg/ml and 7.68 (6.1-7.8) microg/ml respectively. Peak TMP levels at 9 hours
      after a second TMP dose of 5 or 10 mg/kg were 6.98 (3.4-8.8) microg/ml and 9.25
      (8.2-10.3) microg/ml respectively. CONCLUSION: Therapeutic concentrations of TMP
      for treatment of P. jiroveci can be attained with an oral loading dose of 20
      mg/kg and sustained with a second dose at 6 hours of either 5 mg or 10 mg/kg in
      stable HIV-infected children.

PMID- 16909189
TI  - Drug administration errors by South African anaesthetists--a survey.
AB  - OBJECTIVES: To investigate the incidence, nature of and factors contributing
      towards wrong drug administrations by South African anaesthetists. DESIGN: A
      confidential, self-reporting survey was sent out to the 720 anaesthetists on the
      database of the South African Society of Anaesthesiologists. RESULTS: A total of
      133 questionnaires were returned for analysis (18.5% response rate). Of the
      respondents, 125 (94%) admitted to having inadvertently administered a wrong
      drug. Thirty respondents (22.6%) said they had made errors on at least four
      occasions. A total of 303 specific wrong drug administrations were described.
      Nearly 50% involved muscle relaxants. A further 43 incidents (14%) involved the
      erroneous administration of vasoactive drugs. Five deaths and 3 nonfatal cardiac
      arrests were reported. In 9.9% of incidents the anaesthetic time was prolonged by
      more than 30 minutes. Contributory causes identified included syringe swaps
      (40%), misidentification of drugs (27.1%), fatigue (14.1%), distractions (4.7%),
      and mislabelling of syringes (4.7%). Only 19% of respondents regularly use colour
      coded syringe labels complying with the national standard. CONCLUSIONS: Most
      anaesthetists experienced at least one drug error. The incidence of wrong drug
      administrations by South African anaesthetists appears to be similar to that in
      Australasia and Canada. The commonest error was a 'syringe swap' involving muscle
      relaxants. Most drug errors are inconsequential. An important minority of
      incidents result in severe morbidity or death. The study supports efforts to
      improve ampoule labelling, to encourage the use of syringe labels based on the
      international colour code and to develop a national reporting system for such
      incidents.

PMID- 16909190
TI  - Determinants of acute respiratory infections in Soweto--a population-based birth
      cohort.
AB  - BACKGROUND: Acute respiratory infections (ARIs) are an important cause of infant
      morbidity in both developing and developed countries, and they are the leading
      cause of death in poorer parts of the world. Respiratory viruses appear to be the
      most frequent microbiological pathogens, especially respiratory syncytial virus.
      It has been suggested that factors such as being male, overcrowding, poor access
      to medical care, low level of maternal education, and passive smoking are
      associated with contracting ARIs. DESIGN: A fixed birth cohort of 571 children
      was followed from birth to 1 year of age. The children were monitored for
      symptoms of ARIs during regular home visits. SETTING: An urban low-income setting
      in Soweto, a township outside Johannesburg with an estimated 1.2 million
      inhabitants, including an estimated 45,000 children under 2 years of age.
      SUBJECTS: A total of 571 children were observed for 118,650 days. OUTCOME
      MEASURES: The incidence rate of ARIs. The determinants birth weight,
      breastfeeding, gender, crowding, passive smoking, indoor pollution, and sanitary
      facilities were analysed. RESULTS: A total of 489 episodes of coughing or
      coughing and nasal discharge combined were recorded. Only the father's level of
      education and the number of people living in the household remained significant
      in the multivariate analyses. The incidence of severe ARIs was reduced among
      breastfed infants. CONCLUSIONS: Our study supports previous observations
      suggesting that crowding and communal living conditions are important
      determinants of ARIs. Breastfeeding seemed protective against severe ARI. The
      lack of association with well-described risk factors such as low level of
      maternal education, gender and passive smoking could be due to lack of
      statistical power in this rather uniform population.

PMID- 16909191
TI  - Guideline for the management of nosocomial infections in South Africa.
AB  - OBJECTIVE: To write a guideline for the management and prevention of nosocomial
      infections in South Africa in view of the following: Nosocomial infections are a
      common and increasing problem globally, including South Africa. Widely varying
      standards of prevention and management of these important infections. Increasing
      and emerging antimicrobial resistance among commonly isolated pathogens. The
      significant economic burden of these infections on the health care system as well
      as their impact on patient morbidity and mortality. The main aims of the
      guideline are to provide recommendations for the initial choice of antimicrobial
      agents and the appropriate management of these infections encompassing the
      following conditions: (i) nosocomial pneumonia, health care-associated pneumonia
      and ventilator-associated pneumonia; (ii) nosocomial bloodstream infections;
      (iii) nosocomial intravascular infections; (iv) nosocomial urinary tract
      infections; (v) nosocomial intra-abdominal infections; and (vi) nosocomial
      surgical skin and soft-tissue infections. EVIDENCE: Working group of clinicians
      from relevant disciplines, following detailed literature review. RECOMMENDATIONS:
      These include details of the likely pathogens, an appropriate diagnostic
      approach, antibiotic treatment options and appropriate preventive strategies.
      ENDORSEMENT: The guideline document was endorsed by the South African Thoracic
      Society, the Critical Care Society of Southern Africa and the Federation of
      Infectious Diseases Societies of Southern Africa.

PMID- 16909192
TI  - Consumer perspectives on quality of care in the treatment of schizophrenia.
AB  - Guidelines and best practices represent advances in the promotion of quality care
      in the treatment of schizophrenia. These efforts have been primarily developed by
      clinicians and academic researchers, and appropriately focus on
      psychopharmacological treatments. However, including other perspectives in the
      guideline development process may expand what is considered to be quality care.
      This study examines the opinions of forty individuals diagnosed with
      schizophrenia as to what constitutes quality treatment. Results from a thematic
      analysis indicate wide agreement on the importance of good psychopharmacology and
      case management, but respondents also emphasized the importance of a good
      interpersonal process, and the need for psychosocial rehabilitation supports.
      Current practice guideline efforts should consider including interpersonal
      process standards that have been demonstrated to enhance therapeutic
      relationships and ultimately clinical outcomes, and enhance their emphasis on
      psychosocial rehabilitation supports.

PMID- 16909193
TI  - Analysis of risk factors associated with surgical failure of inside-out
      transobturator vaginal tape for treating urodynamic stress incontinence.
AB  - The goals of this study were to assess the efficacy of inside-out transobturator
      vaginal tape (TVT-O) as a treatment of urodynamic stress incontinence (USI) and
      to explore the possible factors determining surgical success and failure. Each
      woman had a 20-min pad test and urodynamic study including uroflowmetry,
      cystometry, and stress urethral pressure profile before and after treatment.
      Forty-six of the 54 women (85%) were cured of the disease, and two (4%) showed
      clinical improvement; TVT-O had failed to treat USI in six patients (11%) during
      the 9-month follow-up period. We assessed the relationship between clinical
      features, urodynamic parameters, and treatment outcome. Of these, only age and
      previous anti-incontinence surgery were significant risk factors for surgical
      failure. The success rate during the 9-month follow-up period decreased
      significantly in women > or =60 years and in women with previous anti
      incontinence surgery. Women with USI can be treated by the TVT-O procedure.

PMID- 16909194
TI  - Result of the tension-free vaginal tape in patients with concomitant prolapse
      surgery: a 2-year follow-up study. An analysis from the Netherlands TVT database.
AB  - This study assessed the long-term outcome of tension-free vaginal tape (TVT) in
      women with concomitant pelvic surgery. A prospective cohort study of 746 patients
      in 41 hospitals was undertaken. The Incontinence Impact Questionnaire (IIQ-7) and
      Urogenital Distress Inventory (UDI-6) were used to measure the results of the
      TVT. Fifty-nine patients with concomitant prolapse surgery were compared with 687
      women with TVT only. The decrease in IIQ/UDI mean scores were statistically
      significant in both groups after the TVT. The success rates of "no leakage at
      all" is comparable for both groups. This study, with 54 gynecologists and
      urologists participating, showed the long-term (2 years) success rates of TVT
      with concomitant prolapse surgery. It shows that the procedure in conjunction
      with prolapse surgery can be safely performed with good results.

PMID- 16909195
TI  - Volumetric bone mineral density and bone size in sleep-deprived individuals.
AB  - INTRODUCTION: Chronic sleep deprivation, which is associated with several age
      related pathologies and altered endocrine function, may adversely affect bone.
      Our a priori hypothesis was that bone mineral density was lower in sleep-deprived
      (<6.5 h/night) vs. sleep-adequate (>6.5-10 h/night) individuals. METHODS: Cross
      sectional analysis of sleep and bone data on 1,146 individuals (652 women) was
      performed. Measurements were obtained at the distal radius by pQCT, and the spine
      and hip by DXA. Bone differences between sleep-deprived and sleep-adequate groups
      were compared after stratifying by sex and controlling for covariates. RESULTS:
      Overall, 19% of the population was sleep deprived. Sleep-deprived women had lower
      cortical volumetric BMD (1,208+/-4 vs. 1,219+/-2 mg/cm(3), P=0.03) than sleep
      adequate women. Sleep-deprived men had lower pSSI, an estimate of torsional
      bending strength, than sleep-adequate men (358+/-10 vs. 382+/-5 mm(3), P=0.04),
      due to a slightly smaller periosteal circumference (43.9+/-0.4 vs. 44.8+/-0.2 mm,
      P=0.07) and cortical area (103+/-2 vs. 106+/-1+/-mm(2), P=0.06). CONCLUSION:
      Sleep deprivation is associated with some, but not all, bone outcomes. These
      findings may have important public health significance given the increasing
      prevalence of sleep deprivation.

PMID- 16909196
TI  - Osteoporosis prevention and therapy: preserving and building strength through
      bone quality.
AB  - While bone mineral density measurements play a central role in osteoporosis
      management, the degree to which increases in this parameter contribute to bone
      fragility, fracture risk, and the therapeutic efficacy of osteoporosis agents is
      controversial. Indeed, bone strength is also significantly dependent upon bone
      turnover and bone quality, including microarchitecture, mineralization, and
      geometry. Given the critical role of these factors, it is essential to understand
      how they are affected by therapeutic agents. Even though a number of
      technological advances, such as microcomputed tomography, magnetic resonance
      imaging, and computerized analysis of radiographic patterns, help to provide
      critical information toward a more comprehensive assessment of bone turnover and
      bone quality, clinical trials addressing these factors are scarce. This article
      provides a review of studies relating to how osteoporosis therapies impact
      parameters of bone strength and quality.

PMID- 16909197
TI  - Novel regulators of RyR Ca2+ release channels: insight into molecular changes in
      genetically-linked myopathies.
AB  - There are many mutations in the ryanodine receptor (RyR) Ca2+ release channel
      that are implicated in skeletal muscle disorders and cardiac arrhythmias. More
      than 80 mutations in the skeletal RyR1 have been identified and linked to
      malignant hyperthermia, central core disease or multi-minicore disease, while
      more than 40 mutations in the cardiac RyR2 lead to ventricular arrhythmias and
      sudden cardiac death in patients with structurally normal hearts. These RyR
      mutations cause diverse changes in RyR activity which either excessively activate
      or block the channel in a manner that disrupts Ca2+ signalling in the muscle
      fibres. In a different myopathy, myotonic dystrophy (DM), a juvenile isoform of
      the skeletal RyR is preferentially expressed in adults. There are two regions of
      RyR1 that are variably spiced and developmentally regulated (ASI and ASII). The
      juvenile isoform (ASI(-)) is less active than the adult isoform (ASI(+)) and its
      over-expression in adults with DM may contribute to functional changes. Finally,
      mutations in an important regulator of the RyR, the Ca2+ binding protein
      calsequestrin (CSQ), have been linked to a disruption of Ca2+ homeostasis in
      cardiac myocytes that results in arrhythmias. We discuss evidence supporting the
      hypothesis that mutations in each of these situations alter protein/protein
      interactions within the RyR complex or between the RyR and its associated
      proteins. The disruption of these protein-protein interactions can lead either to
      excess Ca2+ release or reduced Ca2+ release and thus to abnormal Ca2+
      homeostasis. Much of the evidence for disruption of protein-protein interactions
      has been provided by the actions of a group of novel RyR regulators, domain
      peptides with sequences that correspond to sequences within the RyR and which
      compete with the endogenous residues for their interaction sites.

PMID- 16909199
TI  - A VEGF-A splice variant defective for heparan sulfate and neuropilin-1 binding
      shows attenuated signaling through VEGFR-2.
AB  - The development of functional blood and lymphatic vessels requires spatio
      temporal coordination of the production and release of growth factors such as
      vascular endothelial growth factors (VEGFs). VEGF family proteins are produced in
      multiple isoforms with distinct biological properties and bind to three types of
      VEGF receptors. A VEGF-A splice variant, VEGF-A(165)b, has recently been isolated
      from kidney epithelial cells. This variant is identical to VEGF-A(165) except for
      the last six amino acids encoded by an alternative exon. VEGF-A(165)b and VEGF
      A(165) bind VEGF receptors 1 and 2 with similar affinity. VEGF-A(165)b elicits
      drastically reduced activity in angiogenesis assays and even counteracts
      signaling by VEGF-A(165). VEGF-A(165)b weakly binds to heparan sulfate and does
      not interact with neuropilin-1, a coreceptor for VEGF receptor 2. To determine
      the molecular basis for altered signaling by VEGF-A(165)b we measured VEGF
      receptor 2 and ERK kinase activity in endothelial cells in culture. VEGF-A(165)
      induced strong and sustained activation of VEGF receptor 2 and ERK-1 and -2,
      while activation by VEGF-A(165)b was only weak and transient. Taken together
      these data show that VEGF-A(165)b has attenuated signaling potential through VEGF
      receptor 2 defining this new member of the VEGF family as a partial receptor
      agonist.

PMID- 16909198
TI  - Use of thin filament reconstituted muscle fibres to probe the mechanism of force
      generation.
AB  - The technique of selective removal of the thin filament by gelsolin in bovine
      cardiac muscle fibres, and reconstitution of the thin filament from isolated
      proteins is reviewed, and papers that used reconstituted preparations are
      discussed. By comparing the results obtained in the absence/presence of
      regulatory proteins tropomyosin (Tm) and troponin (Tn), it is concluded that the
      role of Tm and Tn in force generation is not only to expose the binding site of
      actin to myosin, but also to modify actin for better stereospecific and
      hydrophobic interaction with myosin. This conclusion is further supported by
      experiments that used a truncated Tm mutant and the temperature study of
      reconstituted fibres. The conclusion is consistent with the hypothesis that there
      are three states in the thin filament: blocked state, closed state, and open
      state. Tm is the major player to produce these effects, with Tn playing the role
      of Ca2+ sensing and signal transmission mechanism. Experiments that changed the
      number of negative charges at the N-terminal finger of actin demonstrates that
      this part of actin is essential to promote the strong interaction between actin
      and myosin molecules, in addition to the well-known weak interaction that
      positions the myosin head at the active site of actin prior to force generation.

PMID- 16909200
TI  - Cholinesterases are down-expressed in human colorectal carcinoma.
AB  - The aberrations of cholinesterase (ChE) genes and the variation of ChE activity
      in cancerous tissues prompted us to investigate the expression of ChEs in
      colorectal carcinoma. The study of 55 paired specimens of healthy (HG) and
      cancerous gut (CG) showed that acetylcholinesterase (AChE) activity fell by 32%
      and butyrylcholinesterase (BuChE) activity by 58% in CG. Abundant AChE-H, fewer
      AChE-T, and even fewer AChE-R and BuChE mRNAs were observed in HG, and their
      content was greatly diminished in CG. The high level of the AChE-H mRNA explains
      the abundance of AChE-H subunits in HG, which as glycosylphosphatidylinositol
      (GPI)-anchored amphiphilic AChE dimers (G2(A)) and monomers (G1(A)) account for
      69% of AChE activity. The identification of AChE-T and BuChE mRNAs justifies the
      occurrence in gut of A12, G4(H) and PRiMA-containing G4(A) AChE forms, besides
      G4(H), G4(A) and G1(H) BuChE. The down-regulation of ChEs might contribute to gut
      carcinogenesis by increasing acetylcholine availability and over-stimulating
      muscarinic receptors.

PMID- 16909201
TI  - Chronic gestational exposure to ethanol causes insulin and IGF resistance and
      impairs acetylcholine homeostasis in the brain.
AB  - In fetal alcohol syndrome (FAS), cerebellar hypoplasia is associated with
      impaired insulin-stimulated survival signaling. This study characterizes ethanol
      dose-effects on cerebellar development, expression of genes required for insulin
      and insulin-like growth factor (IGF) signaling, and the upstream mechanisms and
      downstream consequences of impaired signaling in relation to acetylcholine (ACh)
      homeostasis. Pregnant Long Evans rats were fed isocaloric liquid diets containing
      0%, 2%, 4.5%, 6.5%, or 9.25% ethanol from gestation day 6. Ethanol caused dose
      dependent increases in severity of cerebellar hypoplasia, neuronal loss,
      proliferation of astrocytes and microglia, and DNA damage. Ethanol also reduced
      insulin, IGF-I, and IGF-II receptor binding, insulin and IGF-I receptor tyrosine
      kinase activities, ATP, membrane cholesterol, and choline acetyltransferase
      (ChAT) expression. In vitro studies linked membrane cholesterol depletion to
      impaired insulin receptor binding and insulin-stimulated ChAT. In conclusion,
      cerebellar hypoplasia in FAS is mediated by insulin/IGF resistance with attendant
      impairments in energy production and ACh homeostasis.

PMID- 16909202
TI  - Molecular characterization of the tumor-associated antigen AAA-TOB3.
AB  - In search for new valuable tumor-associated antigens using the AMIDA technique,
      we identified the KIAA 1273-AAA-TOB3 protein. KIAA 1273 and AAA-TOB3 were
      considered synonyms for the atad3B gene product. We show that the atad3b gene
      encodes two distinct proteins, both overexpressed in head and neck carcinomas and
      required for correct cell division. Both products differ within the N terminus,
      are generated upon distinct transcription initiation sites, and have been termed
      AAA-TOB3s and AAA-TOB3l. Both isoforms are early targets of c-myc and are located
      in mitochondria. A previous report suggested pro-apoptotic properties of the
      murine homolog of AAA-TOB3l. Here, we did not observe any pro-apoptotic effects
      in human cell lines, overexpressing h-AAA-TOB3s or h-AAA-TOB3l. By contrast, the
      specific knock-down of both mRNAs resulted in polynuclear cells and decreased
      proliferation, along with dysfunctional cell division followed by increased
      apoptosis. Thus, the present data suggest a role for AAA-TOB3s/l in tumor
      progression.

PMID- 16909204
TI  - Bardet-Biedl syndrome: an emerging pathomechanism of intracellular transport.
AB  - From a handful of uncloned genetic loci 6 years ago, great strides have been made
      in understanding the genetic and molecular aetiology of Bardet-Biedl syndrome
      (BBS), a rare pleiotropic disorder characterised by a multitude of symptoms,
      including obesity, retinal degeneration and cystic kidneys. Presently, 11 BBS
      genes have been cloned, with the likelihood that yet more BBS genes remain
      undiscovered. In 2003, a major breakthrough was made when it was shown that BBS
      is likely caused by defects in basal bodies and/or primary cilia. Since then,
      studies in numerous animal models of BBS have corroborated the initial findings
      and, in addition, have further refined the specific functions of BBS proteins.
      These include roles in establishing planar cell polarity (noncanonical Wnt
      signaling) in mice and zebrafish, modulating intraflagellar transport and lipid
      homeostasis in worms, and regulating intracellular trafficking and centrosomal
      functions in zebrafish and human tissue culture cells. From these discoveries, a
      common theme has emerged, namely that the primary function of BBS proteins may be
      to mediate and regulate microtubule-based intracellular transport processes.

PMID- 16909203
TI  - Molecular mechanisms of megakaryopoiesis.
AB  - One function of bone marrow megakaryocytes (MKs) is the controlled release of
      platelets into the circulation. Over the past few years, molecular mechanisms
      that contribute to MK development and differentiation have begun to be
      elucidated. This review provides a brief overview of megakaryopoiesis and
      platelet function, and the importance of selected hematopoietic transcription
      factors (including GATA-1, FOG, Fli-1, AML1, and NF-E2) and target genes in this
      biological process. In addition, a discussion of human diseases affecting
      megakaryopoiesis and mouse models of thrombocytopenia are presented with emphasis
      on how these systems have and will continue to provide further insights into
      mechanisms that control the biological functions of the megakaryocytic cell
      lineage. Ultimately, such knowledge may provide the basis for novel therapeutic
      approaches for modulation of platelet number and function.

PMID- 16909205
TI  - Structural and biological aspects of carotenoid cleavage.
AB  - Apo-carotenoid compounds such as retinol (vitamin A) are involved in a variety of
      cellular processes and are found in all kingdoms of life. Instead of being
      synthesized from small precursors, they are commonly produced by oxidative
      cleavage and subsequent modification of larger carotenoid compounds. The cleavage
      reaction is catalyzed by a family of related enzymes, which convert specific
      substrate double bonds to the corresponding aldehydes or ketones. The individual
      family members differ in their substrate preference and the position of the
      cleaved double bond, giving rise to a remarkable number of products starting from
      a limited number of carotenoid substrate molecules. The recent determination of
      the structure of a member of this family has provided insight into the reaction
      mechanism, showing how substrate specificity is achieved. This review will focus
      on the biochemistry of carotenoid oxygenases and the structural determinants of
      the cleavage reaction.

PMID- 16909206
TI  - Actin-targeting natural products: structures, properties and mechanisms of
      action.
AB  - Natural small-molecule inhibitors of actin cytoskeleton dynamics have long been
      recognized as valuable molecular probes for dissecting complex mechanisms of
      cellular function. More recently, their potential use as chemotherapeutic drugs
      has become a focus of scientific investigation. The primary focus of this review
      is the molecular mechanism by which different actin-targeting natural products
      function, with an emphasis on structural considerations of toxins for which high
      resolution structural information of their interaction with actin is available.
      By comparing the molecular interactions made by different toxin families with
      actin, the structural themes of those that alter filament dynamics in similar
      ways can be understood. This provides a framework for novel synthetic-compound
      designs with tailored functional properties that could be applied in both
      research and clinical settings.

PMID- 16909207
TI  - The non-psychoactive cannabidiol triggers caspase activation and oxidative stress
      in human glioma cells.
AB  - Recently, we have shown that the non-psychoactive cannabinoid compound
      cannabidiol (CBD) induces apoptosis of glioma cells in vitro and tumor regression
      in vivo. The present study investigated a possible involvement of caspase
      activation and reactive oxygen species (ROS) induction in the apoptotic effect of
      CBD. CBD produced a gradual, time-dependent activation of caspase-3, which
      preceded the appearance of apoptotic death. In addiction, release of cytochrome c
      and caspase-9 and caspase-8 activation were detected. The exposure to CBD caused
      in glioma cells an early production of ROS, depletion of intracellular
      glutathione and increase activity of glutathione reductase and glutathione
      peroxidase enzymes. Under the same experimental condition, CBD did not impair
      primary glia. Thus, we found a different sensitivity to the anti-proliferative
      effect of CBD in human glioma cells and non-transformed cells that appears
      closely related to a selective ability of CBD in inducing ROS production and
      caspase activation in tumor cells.

PMID- 16909208
TI  - Lysyl oxidase: an oxidative enzyme and effector of cell function.
AB  - Lysyl oxidase (LOX) oxidizes the side chain of peptidyl lysine converting
      specific lysine residues to residues of alpha-aminoadipic-delta-semialdehyde.
      This posttranslational chemical change permits the covalent crosslinking of the
      component chains of collagen and those of elastin, thus stabilizing the fibrous
      deposits of these proteins in the extracellular matrix. Four LOX-like (LOXL)
      proteins with varying degrees of similarity to LOX have been described,
      constituting a family of related proteins. LOX is synthesized as a preproprotein
      which emerges from the cell as proLOX and then is processed to the active enzyme
      by proteolysis. In addition to elastin and collagen, LOX can oxidize lysine
      within a variety of cationic proteins, suggesting that its functions extend
      beyond its role in the stabilization of the extracellular matrix. Indeed, recent
      findings reveal that LOX and LOXL proteins markedly influence cell behavior
      including chemotactic responses, proliferation, and shifts between the normal and
      malignant phenotypes.

PMID- 16909210
TI  - Hepatocyte growth factor differently influences Met-E-cadherin phosphorylation
      and downstream signaling pathway in two models of breast cells.
AB  - E-cadherins are implicated in cell adhesion, and also in cell signaling by
      associating with tyrosine kinase-receptors such as Met, the hepatocyte growth
      factor (HGF) receptor. Using two different cellular models, i.e. MCF-7 (breast
      carcinoma) and MCF-10 (immortalized mammary) cells, we studied the possible
      mechanism(s) by which E-cadherins modulate the signaling pathways downstream of
      Met, leading to beta-catenin-TCF transcriptional activity. In MCF-7, but not in
      MCF-10 cells, E-cadherins were remarkably associated with Met. Moreover, in MCF-7
      cells both co-immunoprecipitation with anti-Met antibody and co-localization were
      increased by 30-min HGF treatment, which caused E-cadherin tyrosine
      phosphorylation. Also beta-catenin in the co-immunoprecipitate was phosphorylated
      by HGF, probably favoring TCF activation. Consistently, after HGF treatment, beta
      catenin redistributed earlier in MCF-7 than in MCF-10 cells, with nuclear
      accumulation and activation of TOPFLASH gene reporter. Our results indicate a
      functional role of Met-E-cadherin interaction in MCF-7 cells through the
      amplification of the signaling downstream of HGF-Met triggering that involved c
      Src and phosphoinositide-3-kinase activities.

PMID- 16909209
TI  - Espins and the actin cytoskeleton of hair cell stereocilia and sensory cell
      microvilli.
AB  - The espins are novel actin-bundling proteins that are produced in multiple
      isoforms from a single gene. They are present at high concentration in the
      parallel actin bundle of hair cell stereocilia and are the target of deafness
      mutations in mice and humans. Espins are also enriched in the microvilli of taste
      receptor cells, solitary chemoreceptor cells, vomeronasal sensory neurons and
      Merkel cells, suggesting that espins play important roles in the microvillar
      projections of vertebrate sensory cells. Espins are potent actin-bundling
      proteins that are not inhibited by Ca2+. In cells, they efficiently elongate
      parallel actin bundles and, thereby, help determine the steadystate length of
      microvilli and stereocilia. Espins bind actin monomer via their WH2 domain and
      can assemble actin bundles in cells. Certain espin isoforms can also bind
      phosphatidylinositol 4,5-bisphosphate, profilins or SH3 proteins. These
      biological activities distinguish espins from other actin-bundling proteins and
      may make them well-suited to sensory cells.

PMID- 16909211
TI  - Taste perception and coding in the periphery.
AB  - Recent identification of taste receptors and their downstream signaling
      molecules, expressed in taste receptor cells, led to the understanding of taste
      coding in the periphery. Ion channels appear to mediate detection of salty and
      sour taste. The sensations of sweet, umami and bitter taste are initiated by the
      interaction of sapid molecules with the G-protein-coupled receptors T1Rs and
      T2Rs. Mice lacking either PLCbeta2 or TRPM5 diminish behavioral and nerve
      responses to sweet, umami and bitter taste stimuli, suggesting that both receptor
      families converge on a common signaling pathway in the taste receptor cells.
      Nevertheless, separate populations of taste cells appear to be uniquely tuned to
      sweet, umami and bitter taste. Since PLCbeta2-deficient mice still respond to
      sour and salty stimuli, sour and salty taste are perceived independent of bitter,
      umami and sweet taste. In this review, the recent characterization of the
      cellular mechanisms underlying taste reception and perception, and of taste
      coding in the periphery will be discussed.

PMID- 16909212
TI  - The Foxa family of transcription factors in development and metabolism.
AB  - The Foxa subfamily of winged helix/forkhead box (Fox) transcription factors has
      been the subject of genetic and biochemical study for over 15 years. During this
      time its three members, Foxa1, Foxa2 and Foxa3, have been found to play important
      roles in multiple stages of mammalian life, beginning with early development,
      continuing during organogenesis, and finally in metabolism and homeostasis in the
      adult. Foxa2 is required for the formation of the node and notochord, and in its
      absence severe defects in gastrulation, neural tube patterning, and gut
      morphogenesis result in embryonic lethality. Foxa1 and Foxa2 cooperate to
      establish competence in foregut endoderm and are required for normal development
      of endoderm-derived organs such as the liver, pancreas, lungs, and prostate. In
      post-natal life, members of the Foxa family control glucose metabolism through
      the regulation of multiple target genes in the liver, pancreas, and adipose
      tissue. Insight into the unique molecular basis of Foxa function has been
      obtained from recent genetic and genomic data, which identify the Foxa proteins
      as 'pioneer factors' whose binding to promoters and enhancers enable chromatin
      access for other tissue-specific transcription factors.

PMID- 16909213
TI  - Internalization of cationic peptides: the road less (or more?) traveled.
AB  - Facilitating the entry of molecules into mammalian cells is of great interest to
      fields as diverse as cell biology and drug delivery. The discovery of natural
      protein transduction domains and the development of artificial ones, including
      polyarginine, provides a means to achieve this goal. Here, we comment on key
      chemical and biological aspects of cationic peptide internalization, including
      the physiological relevance of this process.

PMID- 16909216
TI  - Spectroscopy Challenge 11.

PMID- 16909215
TI  - A cell line (HEW) from embryos of haddock (Melanogrammus aeglefinius) and its
      capacity to tolerate environmental extremes.
AB  - Cell lines can be useful experimental tools for studying marine fish, which are
      often difficult to routinely obtain and maintain in the laboratory. As few cell
      lines are available from coldwater marine fish, cultures were initiated from late
      gastrula embryos of haddock (Melanogrammus aeglefinus) in Leibovitz's L-15 with
      fetal bovine serum (FBS). From one culture, a cell line (HEW) emerged that has
      been grown for close to 100 population doublings, was heteroploid, and expressed
      telomerase activity, all of which suggest HEW is immortal. Growth occurred only
      if FBS was present and was optimal at 12 to 18 degrees C. Usually most cells had
      an epithelial-like morphology, but under some conditions, cells drew up into
      round central bodies from which radiated cytoplasmic extensions with multiple
      branches. These neural-like cells appeared within a few hours of cultures being
      placed at 28 degrees C or being switch to a simple salt solution (SSS). At 28
      degrees C, cells died within 24 h. In SSS, HEW cells survived as a monolayer for
      at least 7 days. The sensitivity of HEW cells to morphological change and their
      capacity to withstand starvation should make them useful for investigating
      cellular responses to environmental stresses.

PMID- 16909214
TI  - Tissue distribution, effects of salinity acclimation, and ontogeny of aquaporin 3
      in the marine teleost, silver sea bream (Sparus sarba).
AB  - The purpose of the present study was to ascertain the tissue-specific expression
      of the water channel protein, aquaporin 3 (AQP3), during salinity acclimation and
      larval development of silver sea bream (Sparus sarba). A cDNA fragment encoding
      aquaporin 3 (aqp3) from silver sea bream gill was cloned and from the deduced
      amino acid sequence a polyclonal antibody was prepared. AQP3 was found to be
      present in gill, kidney, liver, brain, heart, and spleen but not in whole blood.
      The abundance of AQP3 was significantly highest in gills of hypoosmotic (6 ppt)
      and isoosmotic (12 ppt) acclimated sea bream when compared to seawater (33 ppt)
      and hypersaline (50 ppt)- acclimated sea bream. Spleen tissue also displayed
      significantly high levels of AQP3 protein in hypoosmotic and isoosmotic
      salinities whereas the AQP3 abundance in brain, liver, heart, and kidney remained
      unchanged across the range of salinities tested. The ontogenetic profile of AQP3
      was also investigated from developing sea bream larvae and AQP3 was first
      detected at 14 days posthatch (dph) and increased steadily up to 28-46 dph. In
      conclusion, this study has demonstrated that AQP3 expression is modulated in gill
      and spleen tissue of salinity acclimated sea bream and that it can be detected
      relatively early during larval development.

PMID- 16909217
TI  - Primary treatment of the anterior vocal commissure squamous carcinoma.
AB  - Squamous cell carcinoma may involve the anterior commissure (AC) area of the
      laryngeal glottis, and can be grouped morphologically into four groups; (1) tumor
      confined to the AC, (2) tumor involving one cord and the AC, (3) tumor involving
      the AC and a portion of both vocal cords, and (4) tumor involving a greater part
      of one cord and crossing over to involve a variable length of the other cord.
      Some of these patients when evaluated by imaging, either CT and/or MRI, may
      demonstrate thyroid cartilage erosion or involvement, thereby upstaging a T1a,
      T1b into a T3 or a T4 glottic cancer. The majority of patients treated by
      radiotherapy have only been staged clinically, and hence a failure or recurrence
      rate of 15%. In patients treated surgically by endoscopic or external surgery,
      the local recurrence rates are similar at 15%. Therefore, future reporting of
      patients treated with AC involvement should be staged radiologically, to include
      CT or MRI, and documentation of the treatment results be reported in subgroups,
      according to whether there is no cartilage involvement, inner-table cartilage
      erosion, or through-and-through cartilage invasion. Should endoscopic cordectomy
      be used, then the type of surgery performed should be based on the classification
      as suggested by the European Laryngological Society. The use of the above
      recommendations would allow for more meaningful results to be reported and for
      cause specific analysis of failure of treatment techniques applied.

PMID- 16909218
TI  - Options for salvage after failed initial treatment of anterior vocal commissure
      squamous carcinoma.
AB  - Persistence or recurrent cancer in the anterior commissure (AC) after primary
      radiotherapy may remain localized to its pretreatment anatomical site. If so,
      endoscopic CO(2) laser excision, in experienced hands, may achieve complete tumor
      excision and result in cure for many patients. Occasionally, second and third
      recurrences may be similarly salvaged by further endoscopic surgery. The use of
      the vertical hemilaryngectomy is an alternative treatment for similar localized
      lesions, with a higher first time surgical tumor eradication rate, but with a
      more protracted hospitalization and a less satisfactory voice and swallowing
      outcome. In both types of such surgical salvage, CT scanning must demonstrate no
      evidence of cartilage invasion or destruction. When there is evidence of minimal
      thyroid cartilage invasion, then the supracricoid partial laryngectomy is an
      alternative conservation option, and is likely to result in a cure, with the
      retention of a voicing larynx without a stoma. When the tumor has increased in
      size from the original pretreatment dimension and/or site, then imaging must be
      used to identify possible cartilage invasion, in which case the likelihood of
      tumor eradication by endoscopic or external vertical partial laryngectomy is
      highly unlikely. The indications for the routine use of total laryngectomy for
      the treatment of recurrent or persistent cancer involving the AC must be
      reviewed; there is current evidence that cure can be achieved by a less radical
      procedure. However, total laryngectomy may remain the only treatment option for
      advanced or aggressive first time recurrence, or in patients who develop
      subsequent recurrence following previous less aggressive surgery (endoscopic or
      external).

PMID- 16909219
TI  - Virtual positron emission tomography/computed tomography-bronchoscopy:
      possibilities, advantages and limitations of clinical application.
AB  - The aim of this study was to demonstrate the possibilities, advantages and
      limitations of virtual bronchoscopy using data sets from positron emission
      tomography (PET) and computed tomography (CT). Twelve consecutive patients with
      lung cancer underwent PET/CT. PET was performed with F-18-labelled 2-[fluorine
      18]-fluoro-2-deoxy-D: -glucose ((18)F-FDG). The tracheobronchial system was
      segmented with a volume-growing algorithm, using the CT data sets, and visualized
      with a shaded-surface rendering method. The primary tumours and the lymph node
      metastases were segmented for virtual CT-bronchoscopy using the CT data set and
      for virtual PET/CT-bronchoscopy using the PET/CT data set. Virtual CT
      bronchoscopy using the low-dose or diagnostic CT facilitates the detection of
      anatomical/morphological structure changes of the tracheobronchial system.
      Virtual PET/CT-bronchoscopy was superior to virtual CT-bronchoscopy in the
      detection of lymph node metastases (P=0.001), because it uses the CT information
      and the molecular/metabolic information from PET. Virtual PET/CT-bronchoscopy
      with a transparent colour-coded shaded-surface rendering model is expected to
      improve the diagnostic accuracy of identification and characterization of
      malignancies, assessment of tumour staging, differentiation of viable tumour
      tissue from atelectases and scars, verification of infections, evaluation of
      therapeutic response and detection of an early stage of recurrence that is not
      detectable or is misjudged in comparison with virtual CT-bronchoscopy.

PMID- 16909220
TI  - Monitoring therapeutic responses of primary bone tumors by diffusion-weighted
      image: Initial results.
AB  - The purpose of our study was to investigate whether quantitative diffusion
      weighted images (DWI) were useful for monitoring the therapeutic response of
      primary bone tumors. We encountered 18 osteogenic and Ewing sarcomas. Magnetic
      resonance (MR) images were performed in all patients before and after therapy. We
      measured the apparent diffusion coefficient (ADC) values, contrast-to-noise ratio
      (CNR), and tumor volume of the bone tumors pre- and posttreatment. We determined
      change in ADC value, change in CNR on T2-weighted images (T2WI), change in CNR on
      gadopentetate dimeglumine (Gd)-T1-weighted images (Gd-T1WI), and change in tumor
      volume. The bone tumors were divided into two groups: group A was comprised of
      tumors with less than 90% necrosis after treatment and group B of tumors at least
      with 90%. Changes in ADC value, tumor volume, and CNR were compared between the
      groups. Change in the ADC value was statistically greater in group B than that in
      the group A (p = 0.003). There was no significant difference in the changes in
      CNR on T2WI (p = 0.683), in CNR on Gd-T1WI (p = 0.763), and tumor volume (p =
      0.065). The ADC value on DWI is a promising tool for monitoring the therapeutic
      response of primary bone sarcomas.

PMID- 16909221
TI  - The canary in the mind: on the fate of dreams in psychoanalysis and in
      contemporary culture.
AB  - Dreams have been central in the birth and evolution of psychoanalysis. This paper
      explores the remarkable story of the relationship between dreams and
      psychoanalysis as a modern version of the long history of dreams in most healing
      traditions. But psychoanalysis seems to have turned away from dreams as central
      inspiration in a way parallel to the general culture's turn away from dreams and
      the reality of inner life. Yet modern postindustrial culture is transfixed by a
      version of "dream life" in ways just beginning to be understood (e.g., in the
      transformation of ancient interest in the inner screen to the external screen).
      Working with dreams in psychoanalytic psychotherapy was a creative and
      revolutionary act for our forebears. It is even more so today, in ways that are
      discussed in this paper.

PMID- 16909222
TI  - [Dermatohistology laboratory].
AB  - Dermatohistology plays an essential role in the diagnosis of cutaneous tumors and
      inflammatory skin diseases. In order to practice dermatohistology properly, one
      needs not only a well-equipped laboratory but also properly trained
      dermatohistologists and laboratory technicians. We discuss the establishment of a
      dermatohistology laboratory. The technical procedures involved in making slides,
      ranging from traditional H & E stains, through special stains,
      immunohistochemistry and molecular-biological techniques, are viewed. The
      importance of clinical-histologic correlation and the limitations of pure
      histologic diagnostics are demonstrated with illustrative cases.

PMID- 16909223
TI  - Selective in vitro targeting of GRP and NMB receptors in human tumours with the
      new bombesin tracer 177Lu-AMBA.
AB  - PURPOSE: To investigate the in vitro binding properties of a novel radiolabelled
      bombesin analogue, (177)Lu-AMBA, in human neoplastic and non-neoplastic tissues
      selected for their expression of the bombesin receptor subtypes GRP-R, NMB-R and
      BRS-3. METHODS: In vitro receptor autoradiography was performed in cancers
      expressing the various bombesin receptor subtypes. The novel radioligand (177)Lu
      AMBA was used and compared with established bombesin radioligands such as (125)I
      Tyr(4)-bombesin and (125)I-[D-Tyr(6),beta-Ala(11),Phe(13),Nle(14)]-bombesin(6
      14). In vitro incidence of detection of each of the three bombesin receptor
      subtypes was evaluated in each tumour. RESULTS: (177)Lu-AMBA identified all GRP-R
      expressing tumours, such as prostatic, mammary and renal cell carcinomas as well
      as gastrointestinal stromal tumours. (177)Lu-AMBA also identified all NMB
      expressing tumours, but did not detect BRS-3-expressing tumours or BRS-3
      expressing pancreatic islets. GRP-R-expressing peritumoral vessels were heavily
      labelled with (177)Lu-AMBA. In contrast to the strongly GRP-R-positive mouse
      pancreas, the human pancreas was not labelled with (177)Lu-AMBA unless chronic
      pancreatitis was diagnosed. In general, the sensitivity was slightly better with
      (177)Lu-AMBA than with the conventional bombesin radioligands. CONCLUSION: The
      present in vitro study suggests that (177)Lu-AMBA may be a very useful in vivo
      targeting agent for GRP-R-expressing tumours, NMB-R-expressing tumours and GRP-R
      expressing neoangiogenic vessels.

PMID- 16909224
TI  - The regulatory background of nuclear cardiology in Europe: a survey by the
      European Council of Nuclear Cardiology.
AB  - PURPOSE: Nuclear cardiology is a well-validated, non-invasive imaging modality
      that is highly cost-effective as a diagnostic and prognostic tool in the
      evaluation of patients with known or suspected coronary artery disease. However,
      the number of procedures in Europe is very far from that which would be expected
      on the basis of epidemiological data, particularly when comparison is made with
      the USA. As a preliminary step for future action aimed at improving and
      increasing nuclear cardiology practice in Europe, the European Council of Nuclear
      Cardiology performed a survey to identify the regulatory issues and the training
      components pertaining to the practice of nuclear cardiology. METHODS: a
      questionnaire was sent to 31 national nuclear medicine societies and to 40
      national cardiology societies. The main areas covered by the survey were: (1) the
      license requirements, (2) the theoretical and practical aspects of training and
      (3) supervision of the stress test during a nuclear cardiology study. RESULTS:
      The results show that, in a setting of wide heterogeneity of national
      regulations, education and professional practice, nuclear medicine is a
      restricted and closely regulated specialty. This situation guarantees the quality
      and safe use of radionuclides; at the same time, however, it limits integration
      of nuclear medicine into the clinical arena. CONCLUSION: Cardiologists should
      become more involved in nuclear cardiology, to further stimulate the use of this
      powerful diagnostic and prognostic imaging modality.

PMID- 16909225
TI  - (124)I in PET imaging: impact on quantification, radiopharmaceutical development
      and distribution.

PMID- 16909226
TI  - Improved targeting of the alpha(v)beta (3) integrin by multimerisation of RGD
      peptides.
AB  - PURPOSE: The integrin alpha(v)beta(3) is expressed on sprouting endothelial cells
      and on various tumour cell types. Due to the restricted expression of
      alpha(v)beta(3) in tumours, alpha(v)beta(3) is considered a suitable receptor for
      tumour targeting. In this study the alpha(v)beta(3) binding characteristics of an
      (111)In-labelled monomeric, dimeric and tetrameric RGD analogue were compared.
      METHODS: A monomeric (E-c(RGDfK)), dimeric (E-[c(RGDfK)](2)), and tetrameric
      (E{E[c(RGDfK)](2)}(2)) RGD peptide were synthesised, conjugated with DOTA and
      radiolabelled with (111)In. In vitro alpha(v)beta(3) binding characteristics were
      determined in a competitive binding assay. In vivo alpha(v)beta(3) targeting
      characteristics of the compounds were assessed in mice with SK-RC-52 xenografts.
      RESULTS: The IC(50) values for DOTA-E-c(RGDfK), DOTA-E-[c(RGDfK)](2), and DOTA
      E{E[c(RGDfK)](2)}(2)were 120 nM, 69.9 nM and 19.6 nM, respectively. At all time
      points, the tumour uptake of the dimer was significantly higher as compared to
      that of the monomer. At 8 h p.i., tumour uptake of the tetramer (7.40+/
      1.12%ID/g) was significantly higher than that of the monomer (2.30+/-0.34%ID/g),
      p<0.001, and the dimer (5.17+/-1.22%ID/g), p<0.05. At 24 h p.i., the tumour
      uptake was significantly higher for the tetramer (6.82+/-1.41%ID/g) than for the
      dimer (4.22+/-0.96%ID/g), p<0.01, and the monomer (1.90+/-0.29%ID/g), p<0.001.
      CONCLUSION: Multimerisation of c(RGDfK) resulted in enhanced affinity for
      alpha(v)beta(3) as determined in vitro. Tumour uptake of a tetrameric RGD peptide
      was significantly higher than that of the monomeric and dimeric analogues,
      presumably owing to the enhanced statistical likelihood for rebinding to
      alpha(v)beta(3).

PMID- 16909227
TI  - Distribution of pectin and arabinogalactan protein epitopes during organogenesis
      from androgenic callus of wheat.
AB  - The distribution of several arabinogalactan protein and pectic epitopes were
      studied during organogenesis in androgenic callus of wheat. In cell wall of
      mature and degenerating parenchyma cells, the arabinogalactan epitopes JIM4,
      JIM14, JIM16 or LM2 were expressed differently according to the cells location.
      LM2 was observed also in meristematic cells of regenerated shoot buds and leaves.
      Anti-pectin JIM7 labelled the wall of meristematic cells but fluorescence was
      strongest in outer walls of surface cells of callus and shoot buds coated by
      extracellular matrix surface network (ECMSN). During leaves growth the ECMSN
      disappeared, and JIM7 fluorescence decreased. JIM5 epitope was abundant in the
      cell walls lining the intercellular spaces of callus parenchyma and in
      tricellular junctions within regenerated buds and leaves.

PMID- 16909228
TI  - Increased alpha-tocopherol content in soybean seed overexpressing the Perilla
      frutescens gamma-tocopherol methyltransferase gene.
AB  - Tocopherols, with antioxidant properties, are synthesized by photosynthetic
      organisms and play important roles in human and animal nutrition. In soybean,
      gamma-tocopherol, the biosynthetic precursor to alpha-tocopherol, is the
      predominant form found in the seed, whereas alpha-tocopherol is the most
      bioactive component. This suggests that the final step of the alpha-tocopherol
      biosynthetic pathway catalyzed by gamma-tocopherol methyltransferase (gamma-TMT)
      is limiting in soybean seed. Soybean oil is the major edible vegetable oil
      consumed, so manipulating the tocopherol biosynthetic pathway in soybean seed to
      convert tocopherols into more active alpha-tocopherol form could have significant
      health benefits. In order to increase the soybean seed alpha-tocopherol content,
      the gamma-TMT gene isolated from Perilla frutescens was overexpressed in soybean
      using a seed-specific promoter. One transgenic plant was recovered and the
      progeny was analyzed for two generations. Our results demonstrated that the seed
      specific expression of the P. frutescens gamma-TMT gene resulted in a 10.4-fold
      increase in the alpha-tocopherol content and a 14.9-fold increase in the beta
      tocopherol content in T2 seed. Given the relative contributions of different
      tocopherols to vitamin E activity, the activity in T2 seed was calculated to be
      4.8-fold higher than in wild-type seed. In addition, the data obtained on lipid
      peroxidation indicates that alpha-tocopherol may have a role in preventing
      oxidative damage to lipid components during seed storage and seed germination.
      The increase in the alpha-tocopherol content in the soybean seed could have a
      potential to significantly increase the dietary intake of vitamin E.

PMID- 16909229
TI  - Labial flap: a versatile tool in the repair of recurrent perineal canal defects.
AB  - Perineal canal, a not so uncommon deformity in Asian countries, sometimes breaks
      down after the usual techniques of repair. The labial pad of fat with its
      vascular supply provides good tissue for interposition between the rectal and
      perineal suture lines in these cases, with good results.

PMID- 16909230
TI  - Face processing in humans and new world monkeys: the influence of experiential
      and ecological factors.
AB  - This study tests whether the face-processing system of humans and a nonhuman
      primate species share characteristics that would allow for early and quick
      processing of socially salient stimuli: a sensitivity toward conspecific faces, a
      sensitivity toward highly practiced face stimuli, and an ability to generalize
      changes in the face that do not suggest a new identity, such as a face
      differently oriented. The look rates by adult tamarins and humans toward
      conspecific and other primate faces were examined to determine if these
      characteristics are shared. A visual paired comparison (VPC) task presented
      subjects with either a human face, chimpanzee face, tamarin face, or an object as
      a sample, and then a pair containing the previous stimulus and a novel stimulus
      was presented. The stimuli were either presented all in an upright orientation,
      or all in an inverted orientation. The novel stimulus in the pair was either an
      orientation change of the same face/object or a new example of the same type of
      face/object, and the stimuli were shown either in an upright orientation or in an
      inverted orientation. Preference to novelty scores revealed that humans attended
      most to novel individual human faces, and this effect decreased significantly if
      the stimuli were inverted. Tamarins showed preferential looking toward novel
      orientations of previously seen tamarin faces in the upright orientation, but not
      in an inverted orientation. Similarly, their preference to look longer at novel
      tamarin and human faces within the pair was reduced significantly with inverted
      stimuli. The results confirmed prior findings in humans that novel human faces
      generate more attention in the upright than in the inverted orientation. The
      monkeys also attended more to faces of conspecifics, but showed an inversion
      effect to orientation change in tamarin faces and to identity changes in tamarin
      and human faces. The results indicate configural processing restricted to
      particular kinds of primate faces by a New World monkey species, with configural
      processing influenced by life experience (human faces and tamarin faces) and
      specialized to process orientation changes specific to conspecific faces.

PMID- 16909231
TI  - Animal logics: decisions in the absence of human language.

PMID- 16909232
TI  - Effects of the menstrual cycle on looking preferences for faces in female rhesus
      monkeys.
AB  - Fluctuations of ovarian hormones across the menstrual cycle influence a variety
      of social and cognitive behaviors in primates. For example, female rhesus monkeys
      exhibit heightened interest for males and increased agonistic interactions with
      other females during periods of high estrogen levels. In the present study, we
      hypothesized that females' preference for males during periods of high estrogen
      levels is also expressed at the level of face perception. We tested four intact
      females on two face-tasks involving neutral portraits of male and female rhesus
      monkeys, chimpanzees and humans. In the visual preference task (VP), monkeys had
      to touch a button to view a face image. The image remained on the screen as long
      as the button was touched, and the duration of pressing was taken as an index of
      the monkey's looking time for the face stimulus. In the Face-Delayed Recognition
      Span Test (Face-DRST), monkeys were rewarded for touching the new face in an
      increasing number of serially presented faces. Monkeys were tested 5 days a week
      across one menstrual cycle. Blood was collected every other day for analysis of
      estradiol and progesterone. Two of the four females were cycling at the time of
      testing. We did not find an influence of the cycle on Face-DRST, likely due to a
      floor effect. In the VP however, the two cycling individuals looked longer at
      conspecific male faces than female faces during the peri-ovulatory period of the
      cycle. Such effects were absent for human and chimpanzee faces and for the two
      noncycling subjects. These data suggest that ovarian hormones may influence
      females' preferences for specific faces, with heightened preference for male
      faces during the peri-ovulatory period of the cycle. Heightened interest for
      stimuli of significant reproductive relevance during periods of high conception
      risk may help guide social and sexual behavior in the rhesus monkey.

PMID- 16909233
TI  - Stacking of blocks by chimpanzees: developmental processes and physical
      understanding.
AB  - The stacking-block task has been used to assess cognitive development in both
      humans and chimpanzees. The present study reports three aspects of stacking
      behavior in chimpanzees: spontaneous development, acquisition process following
      training, and physical understanding assessed through a cylindrical-block task.
      Over 3 years of longitudinal observation of block manipulation, one of three
      infant chimpanzees spontaneously started to stack up cubic blocks at the age of 2
      years and 7 months. The other two infants began stacking up blocks at 3 years and
      1 month, although only after the introduction of training by a human tester who
      rewarded stacking behavior. Cylindrical blocks were then introduced to assess
      physical understanding in object-object combinations in three infant (aged 3-4)
      and three adult chimpanzees. The flat surfaces of cylinders are suitable for
      stacking, while the rounded surface is not. Block manipulation was described
      using sequential codes and analyzed focusing on failure, cause, and solution in
      the task. Three of the six subjects (one infant and two adults) stacked up
      cylindrical blocks efficiently: frequently changing the cylinders' orientation
      without contacting the round side to other blocks. Rich experience in stacking
      cubes may facilitate subjects' stacking of novel, cylindrical shapes from the
      beginning. The other three subjects were less efficient in stacking cylinders and
      used variable strategies to achieve the goal. Nevertheless, they began to learn
      the effective way of stacking over the course of testing, after about 15 sessions
      (75 trials).

PMID- 16909235
TI  - Pilfering ravens, Corvus corax, adjust their behaviour to social context and
      identity of competitors.
AB  - Like other corvids, food-storing ravens protect their caches from being pilfered
      by conspecifics by means of aggression and by re-caching. In the wild and in
      captivity, potential pilferers rarely approach caches until the storers have left
      the cache vicinity. When storers are experimentally prevented from leaving,
      pilferers first search at places other than the cache sites. These behaviours
      raise the possibility that ravens are capable of withholding intentions and
      providing false information to avoid provoking the storers' aggression for cache
      protection. Alternatively, birds may refrain from pilfering to avoid conflicts
      with dominants. Here we examined whether ravens adjust their pilfer tactics
      according to social context and type of competitors. We allowed birds that had
      witnessed a conspecific making caches to pilfer those caches either in private,
      together with the storer, or together with a conspecific bystander that had not
      created the caches (non-storer) but had seen them being made. Compared to in
      private trials, ravens delayed approaching the caches only in the presence of
      storers. Furthermore, they quickly engaged in searching away from the caches when
      together with dominant storers but directly approached the caches when together
      with dominant non-storers. These findings demonstrate that ravens selectively
      alter their pilfer behaviour with those individuals that are likely to defend the
      caches (storers) and support the interpretation that they are deceptively
      manipulating the others' behaviour.

PMID- 16909234
TI  - The logic of the stimulus.
AB  - This paper examines the contribution of stimulus processing to animal logics. In
      the classic functionalist S-O-R view of learning (and cognition), stimuli provide
      the raw material to which the organism applies its cognitive processes-its logic,
      which may be taxon-specific. Stimuli may contribute to the logic of the
      organism's response, and may do so in taxon-specific ways. Firstly, any non
      trivial stimulus has an internal organization that may constrain or bias the way
      that the organism addresses it; since stimuli can only be defined relative to the
      organism's perceptual apparatus, and this apparatus is taxon-specific, such
      constraints or biases will often be taxon-specific. Secondly, the representation
      of a stimulus that the perceptual system builds, and the analysis it makes of
      this representation, may provide a model for the synthesis and analysis done at a
      more cognitive level. Such a model is plausible for evolutionary reasons:
      perceptual analysis was probably perfected before cognitive analysis in the
      evolutionary history of the vertebrates. Like stimulus-driven analysis, such
      perceptually modelled cognition may be taxon-specific because of the taxon
      specificity of the perceptual apparatus. However, it may also be the case that
      different taxa are able to free themselves from the stimulus logic, and therefore
      apply a more abstract logic, to different extents. This thesis is defended with
      reference to two examples of cases where animals' cognitive logic seems to be
      isomorphic with perceptual logic, specifically in the case of pigeons' attention
      to global and local information in visual stimuli, and dogs' failure to
      comprehend means-end relationships in string-pulling tasks.

PMID- 16909236
TI  - Grey parrot numerical competence: a review.
AB  - The extent to which humans and nonhumans share numerical competency is a matter
      of debate. Some researchers argue that nonhumans, lacking human language, possess
      only a simple understanding of small quantities, generally less than four.
      Animals that have, however, received some training in human communication systems
      might demonstrate abilities intermediate between those of untrained nonhumans and
      humans. Here I review data for a Grey parrot (Psittacus erithacus) that has been
      shown to quantify sets of up to and including six items (including heterogeneous
      subsets) using vocal English labels, to comprehend these labels fully, and to
      have a zero-like concept. Recent research demonstrates that he can also sum small
      quantities. His success shows that he understands number symbols as abstract
      representations of real-world collections, and that his sense of number compares
      favorably to that of chimpanzees and young human children.

PMID- 16909237
TI  - Technical intelligence in animals: the kea model.
AB  - The ability to act on information flexibly is one of the cornerstones of
      intelligent behavior. As particularly informative example, tool-oriented behavior
      has been investigated to determine to which extent nonhuman animals understand
      means-end relations, object affordances, and have specific motor skills. Even
      planning with foresight, goal-directed problem solving and immediate causal
      inference have been a focus of research. However, these cognitive abilities may
      not be restricted to tool-using animals but may be found also in animals that
      show high levels of curiosity, object exploration and manipulation, and
      extractive foraging behavior. The kea, a New Zealand parrot, is a particularly
      good example. We here review findings from laboratory experiments and field
      observations of keas revealing surprising cognitive capacities in the physical
      domain. In an experiment with captive keas, the success rate of individuals that
      were allowed to observe a trained conspecific was significantly higher than that
      of naive control subjects due to their acquisition of some functional
      understanding of the task through observation. In a further experiment using the
      string-pulling task, a well-probed test for means-end comprehension, we found the
      keas finding an immediate solution that could not be improved upon in nine
      further trials. We interpreted their performance as insightful in the sense of
      being sensitive of the relevant functional properties of the task and thereby
      producing a new adaptive response without trial-and-error learning. Together,
      these findings contribute to the ongoing debate on the distribution of higher
      cognitive skills in the animal kingdom by showing high levels of sensorimotor
      intelligence in animals that do not use tools. In conclusion, we suggest that the
      'Technical intelligence hypothesis' (Byrne, Machiavellian intelligence II:
      extensions and evaluations, pp 289-211, 1997), which has been proposed to explain
      the origin of the ape/monkey grade-shift in intelligence by a selection pressure
      upon an increased efficiency in foraging behavior, should be extended, that is,
      applied to some birds as well.

PMID- 16909238
TI  - Categorization of visual stimuli in the honeybee Apis mellifera.
AB  - Categorization refers to the classification of perceptual input into defined
      functional groups. We present and discuss evidence suggesting that stimulus
      categorization can also be found in an invertebrate, the honeybee Apis mellifera,
      thus underlining the generality across species of this cognitive process.
      Honeybees show positive transfer of appropriate responding from a trained to a
      novel set of visual stimuli. Such a transfer was demonstrated for specific
      isolated features such as symmetry or orientation, but also for assemblies
      (layouts) of features. Although transfer from training to novel stimuli can be
      achieved by stimulus generalization of the training stimuli, most of these
      transfer tests involved clearly distinguishable stimuli for which generalization
      would be reduced. Though in most cases specific experimental controls such as
      stimulus balance and discriminability are still required, it seems appropriate to
      characterize the performance of honeybees as reflecting categorization. Further
      experiments should address the issue of which categorization theory accounts
      better for the visual performances of honeybees.

PMID- 16909239
TI  - Is bicarbonate solution tolerated better than Shohl's solution in neonatal renal
      tubular acidosis?

PMID- 16909240
TI  - Gross hematuria in minimal-change disease nephrotic syndrome.

PMID- 16909242
TI  - Secondary failure of plasma therapy in factor H deficiency.
AB  - We report a patient with homozygous factor H deficiency leading to permanent
      alternate complement activation and early onset of the hemolytic uremic syndrome.
      He was successfully treated with weekly infusions of fresh frozen plasma over 4
      years, displaying normal blood pressure while only treated with an angiotensin
      converting enzyme (ACE) inhibitor, a steady level of haptoglobin, low-range
      proteinuria and normal creatinine clearance. By the end of the fourth year of
      treatment, he dramatically developed a relapse of hemolytic and uremic syndrome,
      displaying undetectable haptoglobin, nephrotic range proteinuria and progressive
      renal failure. Despite a ten-fold increase in the dosage of plasma infusion
      through daily plasma exchange, haptoglobin remained undetectable while
      circulating antigenic factor H levels reached 22-24% (normal values 65-140%).
      Three months following the biological onset of the relapse, a bilateral
      nephrectomy was performed owing to uncontrolled hypertension and rapidly
      progressive renal failure. The molecular mechanism of plasma resistance remained
      unclear while antifactor H antibodies were not detected in the plasma. We suggest
      that protracted administration of exogenous factor H might not be a long-term
      strategy in homozygous factor H deficiency.

PMID- 16909241
TI  - Left ventricular mass and heart sympathetic activity after renal transplantation
      in children and young adults.
AB  - Recent studies considered that an increase in sympathetic activity (SA) may be
      responsible for left ventricular hypertrophy (LVH). Before and after renal
      transplantation (RT), we evaluated changes on left ventricular mass (LVM) and SA
      in 40 end-stage renal disease patients between 8 and 35 years old. Hypertension
      (95.0% vs. 71.0%; p=0.005), use of combined antihypertensive drugs (57.5% vs.
      30.0%; p=0.01), and LVH (77.5% vs. 52.5%; p=0.01) significantly decreased after
      RT whereas low-to-high frequency ratio (LF/HF), which represents SA, increased
      (3.1 vs. 5.3; p=0.0001). However, LVM regressors (with decrease on LVM index more
      than 20%) showed a trend of lower change on LF/HF ratio (1.6 vs. 2.4; p= 0.09)
      than nonregressors. Living-donor graft, baseline LVM, use of antihypertensive
      drugs, lower change on LF/HF ratio, and lower systolic blood pressure levels were
      associated with LVM regression in the simple correlation analysis. However, in
      the logistic regression analysis, only baseline LVM and donor type remained in
      the model (R(2)=0.35; p=0.0003). Thus, LVH decreased after RT and was related to
      baseline LVM and living-donor type. However, it is possible that the higher
      persistence of LVH after RT could be explained at least in part by increase in
      heart sympathetic activity and use of immunosuppressors.

PMID- 16909244
TI  - Add-on therapy with angiotensin II receptor 1 blocker in children with chronic
      kidney disease already treated with angiotensin-converting enzyme inhibitors.
AB  - The standard renoprotection is based on the inhibition of the renin-angiotensin
      system (RAS) by angiotensin convertase inhibitors (ACEi) or angiotensin II
      receptor 1 blockers (AT1B). The aim of our study was to analyze the effects of
      the addition of AT1B to ACEi-based renoprotection in children with chronic kidney
      disease. We examined 11 children with a mean age of 10.5 years (range, 0.5-18
      years) with a mean glomerular filtration rate (GFR) of 61+/-61 ml/min/1.73 m(2).
      In four patients, the primary renal disease was hemolytic uremic syndrome, in
      three congenital nephrotic syndrome (CNS), in two reflux nephropathy, prune-belly
      syndrome in one and acute cortical necrosis in one. All patients were treated
      with complex hypotensive ACEi-based therapy. AT1B losartan was added in a mean
      dose of 0.9 mg/kg/day. The change in GFR, proteinuria and blood pressure at two
      12-month intervals before and after adding AT1B was compared. The results showed
      that during the 12 months preceding AT1B therapy, there was no change in blood
      pressure and proteinuria, but the GFR declined in 7 of 11 patients. After the
      12th month of add-on therapy with AT1B, there was a significant decrease in both
      absolute and indexed blood pressure values. Proteinuria decreased in eight
      patients, did not change in one and increased in two, including one with CNS. The
      GFR stabilized or increased in eight patients and decreased in three patients
      with CNS. In 7 of 11 patients, there was a significant, but not threatening
      increase in serum potassium. In conclusion, add-on renoprotection with AT1B added
      to ACEi is safe and significantly improves the renoprotective effects of ACEi
      treatment in children with progressive nephropathies, including patients with
      advanced CKD.

PMID- 16909243
TI  - WT1 mutations in nephrotic syndrome revisited. High prevalence in young girls,
      associations and renal phenotypes.
AB  - WT1 mutations have been considered a rare cause of nephrotic syndrome but recent
      reports challenge this assumption. Exclusion of inherited forms is a basic point
      in any therapeutic strategy to nephrotic syndrome since they do not respond to
      drugs. We screened for WT1 mutations in 200 patients with nephrotic syndrome: 114
      with steroid resistance (SRNS) and 86 with steroid dependence (SDNS) for whom
      other inherited forms of nephrotic syndrome (NPHS2, CD2AP) had been previously
      excluded. Three girls out of 32 of the group with steroid resistance under 18
      years presented classical WT1 splice mutations (IVS9+5G>A, IVS9+4C>T) of Frasier
      syndrome. Another one presented a mutation coding for an amino acid change
      (D396N) at exon 9 that is typical of Denys-Drash syndrome. All presented
      resistance to drugs and developed end stage renal failure within 15 years. Two
      girls of the Frasier group presented a 46 XY karyotype with streak gonads while
      one was XX and had normal gonad morphology. In the two cases with IVS9+5G>A renal
      pathology was characterized by capillary wall thickening with deposition of IgG
      and C3 in one that was interpreted as a membrane pathology. Foam cells were
      diffuse in tubule-interstitial areas. In conclusion, WT1 splice mutations are not
      rare in females under 18 years with SRNS. This occurs in absence of a clear renal
      pathology picture and frequently in absence of phenotype change typical of
      Frasier syndrome. In adults and children with SDNS, screening analysis is of no
      clinical value. WT1 hot spot mutation analysis should be routinely done in
      children with SRNS; if the molecular screening anticipates any further
      therapeutic approach it may modify the long term therapeutic strategy.

PMID- 16909245
TI  - Morphine mouthwashes for painful mucositis.

PMID- 16909248
TI  - The posterior approach for low retrorectal tumors in adults.
AB  - BACKGROUND AND AIMS: Retrorectal tumors are uncommon in adults and arise in
      different tissues in the presacral space. The aim of this study is to evaluate
      early complete surgical resection by a perineal approach as the therapy-of-choice
      for tumors under the sacral promontory. PATIENTS AND METHODS: We evaluated the
      posterior approach, especially intersphincteric and parasacrococcygeal excisions,
      in terms of resectability, morbidity, risk of recurrence, and anal function. The
      records of all patients who underwent a posterior surgical procedure in our
      institution for low-lying retrorectal tumors between 1994 and 2003 were reviewed.
      RESULTS: Sixteen patients (13 women and three men) were included in this study.
      The age range was 21 to 57 years (median of 37 years). Pathological findings
      included ten tailgut cysts, three teratomas, one leiomyoma, one dermoid cyst, and
      one schwannoma. Complete tumor resection was obtained in 15 patients. There was
      one case with a microscopic residual tumor. No postoperative mortality was seen,
      and a minor complication occurred in one patient. There was no anal dysfunction.
      The postoperative course was uneventful, with only one tumor recurrence at 5
      months. The median follow up was 60 months (ranging from 18 to 132 months).
      CONCLUSION: In this study, the posterior approach allows complete resection of
      low retrorectal tumors, with low morbidity, no incontinence, nearly no
      recurrence, and no mortality.

PMID- 16909249
TI  - Results of brace treatment of adolescent idiopathic scoliosis in boys compared
      with girls: a retrospective study of 102 patients treated with the Boston brace.
AB  - The aim of the study was to compare the results of brace treatment of adolescent
      idiopathic scoliosis (AIS) in male patients with matched female patients and to
      assess the effectiveness of bracing of boys in AIS and to discuss the results
      with published data. Between 1987 and 1995, 51 consecutive male patients with AIS
      were treated with the Boston brace. The patients were advised to wear the brace
      23 h/day. The medical records of all patients were reviewed. Cobb angles and
      Risser signs were measured before bracing, in brace, at brace discontinuation and
      at final follow-up. Everyone of 51 male patients was compared with a female
      patient who was treated by the same method and matched by Risser sign, curve
      pattern, curve magnitude and duration of treatment and follow-up time. Compliance
      with brace was noted at every visit. Fourteen boys had worn the brace only during
      nighttime or occasionally and were considered non-compliant. Only compliant
      patients with treatment period > 1 year and follow-up > 1 year after treatment
      were accepted for the analyses of effectiveness of brace treatment and its
      prognostic factors. Thirty-three boys met these inclusion criteria. Bracing was
      considered to have a failure if > 5 degrees progression occurred or if surgery
      was performed. At the final follow-up study progression > 5 degrees was found in
      16/51 (31.4%) of male patients. Corresponding figures of female patients were
      11/51 (21.6%), respectively. In compliant boys progression > 5 degrees occurred
      in 6/33 boys compared with 9/33 girls. The association between risk of
      progression and correction% in brace was statistically significant. The overall
      results of brace treatment of idiopathic scoliosis in male patients were inferior
      compared with matched females. One reason for inferior overall results in boys
      was poor compliance with brace wear. However, brace treatment in AIS may be
      recommended with the same principles in both genders.

PMID- 16909250
TI  - Urinary catheterisation and deep wound infection after hip fracture surgery.
AB  - We have studied the incidence of deep wound infection after hip fracture surgery
      and its relationship to urinary catheterisation. Infection after hemiarthroplasty
      occurred in 16/949 cases and 10/1,143 sliding hip screw fixations. No cases of
      deep sepsis were seen for the 203 patients treated with an intramedullary nail or
      the 816 patients treated with parallel screws. The use of urinary catheterisation
      was compared with a control group of patients. In the sepsis group, 12/18
      patients had been catheterised peri-operatively or within 24 h, as opposed to
      18/36 patients in the control group; the difference between these two groups was
      not statistically significant (P=0.38). There was a statistically significant
      increase in the proportion of patients who had more than two urinary
      catheterisations (6/18 versus 3/36, P=0.05) or who had a long-term catheter (7/16
      versus 3/36, P=0.01) in the sepsis group.

PMID- 16909251
TI  - Bone scintigraphy--a wasteful resource in fractures of the neck of the femur.

PMID- 16909252
TI  - Histologically verified lung metastases in benign giant cell tumours--14 cases
      from a single institution.
AB  - From 1975 to 1997, 649 cases of benign giant cell tumours of the bone were
      treated at the Istituto Rizzoli. Fourteen patients (2.1%) experienced lung
      metastases after a mean of 35.2 months. The time interval between the diagnosis
      and the appearance of the lung metastases ranged from 3 months to 11.9 years.
      Metastasectomy was performed in all patients. Histologically, the metastases were
      identical to the primary bone lesions. Two patients with unresectable multiple
      metastases received additional chemotherapy. After a follow-up of 70 months
      (range: 8.2 to 185 months), all patients are alive. Ten patients showed no
      evidence of disease, one of these after a second resection of metastases, and
      four patients presented stable disease with multiple lung metastases. Local
      recurrence of the bone lesion occurred in seven patients before or simultaneously
      to the metastases. In contrast to previous reports, we could not detect a
      predominance of the distal radius, but all of the patients had a stage III tumour
      according to the Enneking criteria of benign lesions. We conclude that even
      metastatic benign giant cell tumours have an excellent prognosis after adequate
      resection. No prognostic factors despite high-grade lesions were detectable.

PMID- 16909253
TI  - Augmentation of tendon attachment to porous ceramics by bone marrow stromal cells
      in a rabbit model.
AB  - Tendon attachment to interconnected porous calcium hydroxyapatite ceramics (IP
      CHA) with cultured bone marrow stromal cells (BMSC) was analysed. The purpose of
      this study was to evaluate whether BMSC in IP-CHA could augment the tendon
      attachment to IP-CHA histologically and biomechanically. Eighteen Japanese white
      rabbits were used. Cultured BMSCs were subcultured in IP-CHA. The grafted tendon
      and IP-CHA with BMSC complex were implanted in a bone defect of the knee [BMSC(+)
      group]. In the contralateral knee, a tendon and IP-CHA without BMSC complex were
      implanted [BMSC(-) group]. Histological findings of the interface between the
      tendon and IP-CHA were similar in the two groups 3 weeks after the operation.
      However, 6 weeks after the operation, more abundant bone formation around the
      tendon was observed in the BMSC(+) group. The direct apposition of the tendon to
      bone in pores and collagen fibre continuity between the tendon and fibrous tissue
      in pores were observed. In biomechanical evaluation, the maximum pull-out load of
      the tendon from the IP-CHA in the BMSC(+) group was significantly higher than
      that in the BMSC(-) group 6 weeks after the operation. BMSCs cultured in IP-CHA
      could augment tendon attachment to IP-CHA.

PMID- 16909254
TI  - External fixation of complex femoral shaft fractures.
AB  - Conversion of temporary external fixation to an intramedullary nail within the
      first 2 weeks after a femoral shaft fracture is standard practice. However, due
      to financial constraints, in large parts of the world external fixation of
      femoral shaft fractures is often the definitive treatment. Out of 60 fractures,
      47 were followed-up for a minimum period of 39 weeks. The average follow-up time
      was 75 weeks. Fourteen fractures were closed, and 33 open. Forty-four fractures
      united at an average of 31 weeks. There were four non-unions, three of them
      infected. Secondary surgical procedures were performed for four non-unions and in
      eight cases of delayed union. One re-fracture occurred, which was successfully
      treated with repeat external fixation. Only six patients regained full range of
      motion. The average flexion was 72 degrees . Pin tract infections occurred in 26
      patients, leading to loosening of four pins. Satisfactory results can be obtained
      with definitive external fixation of femoral shaft fractures. Pin tract
      infections, although a common occurrence, are not a major problem and can be
      treated by local wound care and antibiotic therapy. The most common problem is
      significant decrease in the range of motion of the knee.

PMID- 16909255
TI  - Has the management of shoulder dislocation changed over time?
AB  - Anterior shoulder dislocation is a disabling injury affecting all ages, young and
      old alike. Recently, the treatment of traumatic shoulder dislocation has included
      immobilisation for varying periods of time followed by physiotherapy. This study
      is the first in this country to address the demographic data and recurrence rates
      of shoulder dislocation. Three hundred and eight patients (170 men and 138 women)
      were followed up for an average of 5.9 years. The most frequent mechanism of
      injury was a fall (65.66% of cases), and in 92.1% of the patients, the shoulder
      was reduced in the Emergency Department without the need for sedation or general
      anaesthesia. The overall recurrence rate in all ages was 50%, but rose to 88.9%
      in the 14-20-year age group. The duration of immobilisation did not affect the
      rate of re-dislocation of the humeral head. We believe that conventional shoulder
      immobilisation in a sling offers no benefits, and it would be preferable not to
      immobilise the shoulder at all.

PMID- 16909256
TI  - Synapse development: still looking for the forest, still lost in the trees.
AB  - Synapse development in the vertebrate central nervous system is a highly
      orchestrated process occurring not only during early stages of brain development,
      but also (to a lesser extent) in the mature nervous system. During development,
      the formation of synapses is intimately linked to the differentiation of neuronal
      cells, the extension of their axons and dendrites, and the course wiring of the
      nervous system. Subsequently, the stabilization, elimination, and strengthening
      of synaptic contacts is coupled to the refinement of axonal and dendritic arbors,
      to the establishment of functionally meaningful connections, and probably also to
      the day-to-day acquisition, storage, and retrieval of memories, higher order
      thought processes, and behavioral patterns.

PMID- 16909257
TI  - [Injector implantation of a scleral-fixated intraocular lens].
AB  - BACKGROUND: In this pilot study, a new injector technique for small-incision
      implantation of scleral-fixated intraocular lenses (IOLs) was evaluated for IOL
      stability and visual rehabilitation. PATIENTS AND METHODS: Secondary lens
      implantation was performed in 18 aphakic eyes using a new small incision
      technique with injector implantation. This allowed for haptic suturing with the
      lens body inside the cartridge. All patients were followed-up for best-corrected
      visual acuity, refraction, IOL evaluation and ultrasound biomicroscopy. RESULTS:
      In all eyes the IOL was stable without tilt or torque. Best-corrected visual
      acuity improved 2.2 ETDRS lines after 1 week and 3.1 lines after a mean follow-up
      time of 7.9+/-2.8 months. Two eyes were complicated with small, peripheral
      transillumination defects (n=2), but no pigmentary glaucoma occurred. CONCLUSION:
      By using a self-sealing tunnel incision and injector technique, significant fluid
      egress and consecutive transient hypotony is minimized throughout the whole
      procedure. The technique shows a high IOL stability without tilt and assures
      rapid visual rehabilitation.

PMID- 16909259
TI  - Phenological models for blooming of apple in a mountainous region.
AB  - Six phenological series were available for 'Golden Delicious' apple blooming at
      six sites in Trentino, an alpine fruit-growing region. Several models were tested
      to predict flowering dates, all involving a "chilling and forcing" approach. In
      many cases, application of the models to different climatic conditions results in
      low accuracy of prediction of flowering date. The aim of this work is to develop
      a model with more general validity, starting from the six available series, and
      to test it against five other phenological series outside the original area of
      model development. A modified version of the "Utah" model was the approach that
      performed best. In fact, an algorithm using "chill units" for rest completion and
      a thermal sum for growing-degree-hours (GDH), whose efficiency changes over time
      depending on the fraction of forcing attained, yielded a very good prediction of
      flowering. Results were good even if hourly temperatures were reconstructed from
      daily minimum and maximum values. Errors resulting from prediction of flowering
      data were relatively small, and root mean square errors were in the range of 1-6
      days, being <2 days for the longest phenological series. In the most general form
      of the model, the summation of GDH required for flowering is not a fixed value,
      but a function of topoclimatic variables for a particular site: slope, aspect and
      spring mean temperature. This approach allows extension of application of the
      model to sites with different climatic features outside the test area.

PMID- 16909258
TI  - The ultrastructure of the kinetochore and kinetochore fiber in Drosophila somatic
      cells.
AB  - Drosophila melanogaster is a widely used model organism for the molecular
      dissection of mitosis in animals. However, despite the popularity of this system,
      no studies have been published on the ultrastructure of Drosophila kinetochores
      and kinetochore fibers (K-fibers) in somatic cells. To amend this situation, we
      used correlative light (LM) and electron microscopy (EM) to study kinetochores in
      cultured Drosophila S2 cells during metaphase, and after colchicine treatment to
      depolymerize all microtubules (MTs). We find that the structure of attached
      kinetochores in S2 cells is indistinct, consisting of an amorphous inner zone
      associated with a more electron-dense peripheral surface layer that is
      approximately 40-50 nm thick. On average, each S2 kinetochore binds 11+/-2 MTs,
      in contrast to the 4-6 MTs per kinetochore reported for Drosophila spermatocytes.
      Importantly, nearly all of the kinetochore MT plus ends terminate in the
      peripheral surface layer, which we argue is analogous to the outer plate in
      vertebrate kinetochores. Our structural observations provide important data for
      assessing the results of RNAi studies of mitosis, as well as for the development
      of mathematical modelling and computer simulation studies in Drosophila and
      related organisms.

PMID- 16909260
TI  - High proton relaxivity for gadolinium oxide nanoparticles.
AB  - OBJECTIVE: Nanosized materials of gadolinium oxide can provide high-contrast
      enhancement in magnetic resonance imaging (MRI). The objective of the present
      study was to investigate proton relaxation enhancement by ultrasmall (5 to 10 nm)
      Gd(2)O(3) nanocrystals. MATERIALS AND METHODS: Gd(2)O(3) nanocrystals were
      synthesized by a colloidal method and capped with diethylene glycol (DEG). The
      oxidation state of Gd(2)O(3) was confirmed by X-ray photoelectron spectroscopy.
      Proton relaxation times were measured with a 1.5-T MRI scanner. The measurements
      were performed in aqueous solutions and cell culture medium (RPMI). RESULTS:
      Results showed a considerable relaxivity increase for the Gd(2)O(3)-DEG particles
      compared to Gd-DTPA. Both T (1) and T (2) relaxivities in the presence of
      Gd(2)O(3)-DEG particles were approximately twice the corresponding values for Gd
      DTPA in aqueous solution and even larger in RPMI. Higher signal intensity at low
      concentrations was predicted for the nanoparticle solutions, using experimental
      data to simulate a T(1)-weighted spin echo sequence. CONCLUSION: The study
      indicates the possibility of obtaining at least doubled relaxivity compared to Gd
      DTPA using Gd(2)O(3)-DEG nanocrystals as contrast agent. The high T (1)
      relaxation rate at low concentrations of Gd(2)O(3) nanoparticles is very
      promising for future studies of contrast agents based on gadolinium-containing
      nanocrystals.

PMID- 16909261
TI  - Type IV-a choledochal cyst--a rare adolescent presentation as acute abdomen.
AB  - A 17-year-old adolescent girl from El Salvador presented to the emergency room
      (ER) with severe abdominal pain associated with one episode of nausea and
      vomiting. The pain that started 5 days earlier was sharp in nature and epigastric
      in location with radiation to back and was relieved by half a tablet of Vicodin.
      The patient has a history of intermittent epigastric pain for the past 2 years
      and was treated for Helicobacter pylori for 1 year. In the ER, the serum
      chemistry demonstrated elevated amylase. Further workup with abdominal
      ultrasonography (US), computed tomography (CT), magnetic resonance
      cholangiopancreatography (MRCP), and hepatobiliary scintigraphy confirmed a type
      IV-a choledochal cyst with intra- and extrahepatic dilation of bile ducts. We
      report an unusual acute abdomen presentation of type IV-a choledochal cyst in a
      17-year-old young adult from El Salvador.

PMID- 16909262
TI  - Tissue shrinkage after fixation with formalin injection of prostatectomy
      specimens.
AB  - Prostate cancer volume correlates with stage, grade, and progression after
      prostatectomy. When tumor volume is measured planimetrically, results are
      multiplied by a correction factor to compensate for tissue shrinkage caused by
      processing. Injection of formalin into prostatectomy specimens was suggested for
      improved fixation. Our aim was to investigate how this affects the prostate
      volume. We studied 142 radical prostatectomy specimens. All prostates were
      immersed in 10% formalin. In 84 prostates (59%) we also injected 20 ml of
      formalin before routine fixation. The prostates were weighed unfixed after
      injection and after final fixation. The specimens were sliced and totally
      embedded. The transverse diameters of the prostates were measured on unfixed
      specimens and microscopic sections. The average weight loss after final fixation
      was 5.8 and 8.6% for formalin-injected specimens and standard-fixed specimens,
      respectively (p<0.001). However, when total shrinkage was estimated from the
      transverse diameters, there was no difference related to fixation technique
      (p=0.59). The average linear shrinkage was 4.5%, corresponding to a volume
      correction factor of 1.15. We conclude that formalin injection for fixation of
      prostate tissue does not influence tumor volume calculation compared to
      conventional fixation.

PMID- 16909264
TI  - Dissolved oxygen as principal parameter for conidia production of biocontrol
      fungi Trichoderma viride in non-Newtonian wastewater.
AB  - Dissolved oxygen (DO) concentration was selected as a principal parameter for
      translating results of shake flask fermentation of Trichoderma viride (biocontrol
      fungi) to a fermenter scale. All fermentations were carried out in a 7.5 l
      automated fermenter with a working volume of 4 l. Fermentation performance
      parameters such as volumetric oxygen transfer coefficient (k (L) a), oxygen
      uptake rate (OUR), rheology, conidia concentration, glucose consumption, soluble
      chemical oxygen demand, entomotoxicity and inhibition index were measured. The
      conidia concentration, entomotoxicity and inhibition index were either stable or
      improved at lower DO concentration (30%). Variation of OUR aided in assessing the
      oxygen supply capacity of the fermenter and biomass growth. Meanwhile,
      rheological profiles demonstrated the variability of wastewater during
      fermentation due to mycelial growth and conidiation. In order to estimate power
      consumption, the agitation and the aeration requirements were quantified in terms
      of area under the curves, agitation vs. time (rpm h), and aeration vs. time (lpm
      h). This simple and novel strategy of fermenter operation proved to be highly
      successful which can be adopted to other biocontrol fungi.

PMID- 16909265
TI  - Pullulan production by tropical isolates of Aureobasidium pullulans.
AB  - Tropical isolates of Aureobasidium pullulans previously isolated from distinct
      habitats in Thailand were characterized for their capacities to produce the
      valuable polysaccharide, pullulan. A. pullulans strain NRM2, the so-called "color
      variant" strain, was the best producer, yielding 25.1 g pullulan l(-1) after 7
      days in sucrose medium with peptone as the nitrogen source. Pullulan from strain
      NRM2 was less pigmented than those from the other strains and was remarkably pure
      after a simple ethanol precipitation. The molecular weight of pullulan from all
      cultures dramatically decreased after 3 days growth, as analyzed by high
      performance size exclusion chromatography. Alpha-amylase with apparent activity
      against pullulan was expressed constitutively in sucrose-grown cultures and
      induced in starch-grown cultures. When the alpha-amylase inhibitor acarbose was
      added to the culture medium, pullulan of slightly higher molecular weight was
      obtained from late cultures, supporting the notion that alpha-amylase plays a
      role in the reduction of the molecular weight of pullulan during the production
      phase.

PMID- 16909266
TI  - Contribution by Saccharomyces cerevisiae yeast to fermentative flavour compounds
      in wines from cv. Albarino.
AB  - A comparative study was made of the fermentation products of Spanish Albarino
      wines produced with spontaneous yeast flora and an indigenous selected
      Saccharomyces cerevisiae strain (Alb16). The content of fermentative volatile
      compounds was determined by gas-chromatography-FID. Fifteen compounds (5
      alcohols, 7 esters and 3 acetates) were identified in the two Albarino wines
      studied. Higher alcohols, ethyl esters (except ethyl hexanoate and ethyl
      octanoate) and acetates were in greater concentration in the spontaneous
      fermentation wine than in that with selected Alb16 strain. Principal components
      analysis showed good separation between the different wines.

PMID- 16909267
TI  - Hyperinduction of nitrilases in filamentous fungi.
AB  - 2-Cyanopyridine proved to act as a powerful nitrilase inducer in Aspergillus
      niger K10, Fusarium solani O1, Fusarium oxysporum CCF 1414, Fusarium oxysporum
      CCF 483 and Penicillium multicolor CCF 2244. Valeronitrile also enhanced the
      nitrilase activity in most of the strains. The highest nitrilase activities were
      produced by fungi cultivated in a Czapek-Dox medium with both 2-cyanopyridine and
      valeronitrile. The specific nitrilase activities of these cultures were two to
      three orders of magnitude higher than those of cultures grown on other nitriles
      such as 3-cyanopyridine or 4-cyanopyridine.

PMID- 16909268
TI  - Comparative analysis of mixing distribution in aerobic stirred bioreactor for
      simulated yeasts and fungus broths.
AB  - The study on mixing distribution for an aerobic stirred bioreactor and simulated
      (solutions of carboxymethylcellulose sodium salt), yeasts (S. cerevisiae) and
      fungus (P. chrysogenum pellets and free mycelia) broths indicated the significant
      variation of mixing time on the bioreactor height. The experiments suggested the
      possibility to reach a uniform mixing in whole bulk of the real broths for a
      certain value of rotation speed or biomass concentration domain. For S.
      cerevisiae broths the optimum rotation speed increased to 500 rpm with the
      biomass accumulation from 40 to 150 g/l d.w. Irrespective of their morphology,
      for fungus cultures the existence of optimum rotation speed (500 rpm) has been
      recorded only for biomass concentration below 24 g/l d.w. The influence of
      aeration rate depends on the apparent viscosity/biomass concentration and on the
      impellers and sparger positions. By increasing the apparent viscosity for
      simulated broths, or biomass amount for real broths, the shape of the curves
      describing the mixing time variation is significantly changed for all the
      considered positions. The intensification of the aeration induced the increase of
      mixing time, which reached a maximum value, decreasing then, due to the flooding
      phenomena. This variation became more pronounced at higher viscosities for
      simulated broths, at higher yeasts concentration, and at lower pellets or
      filamentous fungus concentration, respectively. By means of the experimental data
      and using MATLAB software, some mathematical correlations for mixing time have
      been proposed for each broth and considered position inside the bioreactor. These
      equations offer a good agreement with the experiment, the maximum deviation being
      +/-7.3% for S. cerevisiae broths.

PMID- 16909269
TI  - Fermentative production of superoxide dismutase with Kluyveromyces marxianus.
AB  - This work sought to develop a fermentative process for the microbial production
      of superoxide dismutase (SOD), to overcome extraction from animal tissues. Twenty
      eight wild-type yeast strains were screened for SOD productivity. Kluyveromyces
      marxianus L3 showed the highest SOD activity (62 U mg(-1)) and was used for
      process development. Oxidative stress conditions and parameters affecting oxygen
      transfer rate were exploited to improve production. The effects of dilution rate
      (0.067 vs 0.2 h(-1)), aeration pressure (0.3 vs 1.2 bar) and H(2)O(2) (0 vs 50
      mM) were studied during chemostat experiments. Low dilution rate, high pressure
      and H(2)O(2) resulted in an increase in CuZn-SOD up to 475 U mg(-1). When a
      regulation of oxygen saturation was applied during batch cultures, CuZn-SOD was
      progressively higher at 60, 80 and 90% dissolved oxygen tension (DOT) (250, 330
      and 630 U mg(-1), respectively). Furthermore, the highest growth rate and biomass
      yield were achieved at 90% DOT, this being therefore the best DOT condition for
      high overall productivity. Growth and productivity on different carbon sources
      were compared. Specific activity was higher on glycerol than on lactose or
      glucose (496, 454 and 341 U mg(-1), respectively). The highest biomass yield was
      achieved on lactose. It may be therefore the best substrate for SOD production.

PMID- 16909270
TI  - Association of TNF-alpha -308 G/A polymorphism with responsiveness to TNF-alpha
      blockers in rheumatoid arthritis: a meta-analysis.
AB  - Tumor necrosis factor (TNF) antagonists are among the most effective therapies
      for rheumatoid arthritis (RA), yet not all patients show a response. Using meta
      analysis, this present study was designed to investigate whether or not the TNF
      alpha promoter -308 A/G polymorphism is associated with responsiveness to anti
      TNF therapy in RA patients. We performed an exhaustive search for studies that
      examined the association of the TNF-alpha promoter -308 A/G polymorphism and
      responsiveness of anti-TNF therapy in RA using MEDLINE citations and manual
      review. Meta-analysis was performed for A allele carrier (genotypes A/A + A/G)
      between responders to anti-TNF therapy and a non-responder group in a random
      effects model. A total of 6 studies met the inclusion criteria. The number of
      patients in individual studies ranged from 33 to 123. There were 311 RA patients
      who were included in this meta-analysis. There was no heterogeneity between
      studies (I (2) = 0%, P = 0.42). The overall OR for the A allele carrier status
      was significantly decreased in the responder group (OR = 0.33, 95% confidence
      interval = 0.17-0.63, P = 0.0008). The frequency of the A allele carrier was
      53/240 (22.1%) in responders and 32/71 (45.1%) in non-responders. Patients not
      responding to anti-TNF therapy showed an increased frequency of the A allele. The
      meta-analysis of the available data shows a significant association between the
      TNF-alpha promoter -308 A/G polymorphism and responsiveness to anti-TNF therapy,
      suggesting that the individuals with RA who carry the A allele have a poorer
      response to anti-TNF therapy than those with the G allele.

PMID- 16909271
TI  - Cascade of sigma factors in streptomycetes: identification of a new
      extracytoplasmic function sigma factor sigmaJ that is under the control of the
      stress-response sigma factor sigmaH in Streptomyces coelicolor A3(2).
AB  - By using the previously established Escherichia coli two-plasmid system, we
      identified a promoter recognized by the Streptomyces coelicolor A3(2) stress
      response sigma factor sigmaH. The promoter directed expression of the sigJ gene
      encoding an extracytoplasmic function (ECF) sigma factor. S1-nuclease mapping
      using RNA prepared from E. coli containing the two-plasmid system, and S.
      coelicolor A3(2) from various developmental stages identified an identical
      transcription start point in both strains, corresponding to the sigJp promoter.
      The sigJp promoter was induced during sporulation of aerial hyphae. The level of
      the transcript from sigJp was dramatically reduced in a S. coelicolor A3(2) sigH
      mutant and unaffected in a sigF mutant. The S. coelicolor A3(2) core RNA
      polymerase, after complementation with sigmaH, was able to recognize the sigJp
      promoter in vitro. A sigJ mutation had no obvious effect on growth, stress
      response, differentiation, and production of antibiotics. The results suggested
      that the S. coelicolor A3(2) sigJ gene is under the control of stress-response
      sigmaH, thus indicating a cascade of sigma factors in Streptomyces stress
      response and development. Considering the expression of sigJ and its direct
      dependence upon developmentally-regulated sigmaH, we assume that sigmaJ may play
      a role in the later stages of development of S. coelicolor A3(2).

PMID- 16909272
TI  - Iterative cooperation between parallel pathways for object and background motion.
AB  - In a typical visual scene, one or more objects move relative to a larger
      background, which can itself be in motion as a result of the observer's eyes
      moving with respect to the outside world. Here we show that accurate estimation
      of the background motion from an image velocity field can be accomplished through
      an iterative cooperation between two modules: one that specializes in calculating
      a weighted average velocity and another one calculating a velocity contrast map.
      We build on our analysis to provide a model for the tectum-pretectum loop in the
      nonmammalian midbrain. Our model accounts for some of the known properties of the
      tectal neurons (sensitivity to relative motion) and pretectal neurons
      (sensitivity to whole-field motion). It also agrees with our knowledge of the
      pretectotectal projection (divergent and inhibitory), and with the results of
      lesion studies in which the pretectal input to the tectum was removed, leading to
      hyperactivity of the tectal neurons and the animal. Our model also makes a
      testable prediction regarding the tectopretectal projection, i.e., that the
      presence of a larger object and a bigger discrepancy between the directions of
      motion for the object and the background lead to a larger error by the pretectum
      in estimating the background motion when the tectal input is abolished.

PMID- 16909273
TI  - A comparative study of the pharmacokinetics of ibuprofen arginate versus
      dexibuprofen in healthy volunteers.
AB  - OBJECTIVE: Ibuprofen arginate is a salt formulation of ibuprofen designed to
      reach target concentrations rapidly. The primary objective of this study was to
      compare the 12-h pharmacokinetic profile of S(+)-ibuprofen following
      administration of single doses of ibuprofen arginate (600 mg) and dexibuprofen
      (400 mg) in healthy volunteers. METHODS: Twenty-four volunteers were recruited
      into an open-label, randomised, two-period, single-centre study with crossover
      design. RESULTS: Both treatments were well tolerated. Ibuprofen arginate and
      dexibuprofen showed similar bioavailability for S(+)-ibuprofen. Compared with
      dexibuprofen, ibuprofen arginate demonstrated a 45% higher maximum concentration
      (C(max)), and a time to peak concentration (T(max)) 2 h sooner. CONCLUSION:
      Ibuprofen arginate approaches maximum concentrations of S(+)-ibuprofen faster and
      higher than dexibuprofen.

PMID- 16909274
TI  - UGT1A polymorphisms in a Swedish cohort and a human diversity panel, and the
      relation to bilirubin plasma levels in males and females.
AB  - OBJECTIVES: The objective of this study was to investigate the prevalence of
      different polymorphisms and haplotypes associated with individual variations in
      pharmacokinetics and drug toxicity in the uridine-diphosphate glucuronosyl
      transferase (UGT) 1A gene in a Swedish cohort (248 healthy volunteers) and in 14
      different ethnic groups. We also estimated UGT1A genotype-dependent
      glucuronidation efficiency using the endogenous substrate bilirubin as an
      indicator. METHODS: Pyrosequencing-based genotyping assays were used to determine
      the different polymorphisms and haplotypes. RESULTS: Haplotype analysis of the
      UGT1A1 (*1*28), UGT1A6 (*1*2), and UGT1A7(*1*2*3*4) allelic variants showed that
      three major haplotypes constituted 84% of the allelic variants in the cohort. We
      identified 15 haplotypes altogether from all groups, including previously
      undescribed haplotypes. Testing for the association of genotype and total
      bilirubin levels (nonfasting) in plasma disclosed that homozygous carriers of the
      TA allele, irrespective of haplotype combinations, had increased levels of
      bilirubin compared with noncarriers, but a gender-associated difference was
      observed. CONCLUSIONS: In a Swedish cohort, several genetic variants in the UGT1A
      gene are common, but prevalence in a population may differ because of ethnicity.
      A phenotype based on bilirubin levels has limitations in serving as an indicator
      of pharmacogenetic differences in glucuronidation due to the influence of gender.
      Because of possible substrate overlap regarding different UGT1A isoforms,
      determination of haplotypes of potential cis-acting polymorphisms in the UGT1A
      gene should be considered in pharmacogenetic association studies regarding drugs
      that undergo glucuronidation.

PMID- 16909275
TI  - [The value of laparoscopic kidney surgery in urology].
AB  - Since the first laparoscopic nephrectomy in 1990, most ablative and
      reconstructive urological kidney surgery has been attempted laparoscopically. The
      advantages of this method were first demonstrated for benign diseases, with less
      postoperative pain, shorter hospitalization, faster convalescence and, for the
      objective evaluation of these findings, with lower serum levels of interleukins
      and acute phase proteins, and without disadvantages in therapy efficiency. Over
      the last few years, sufficient data have been published to show the oncological
      outcome for patients with kidney cancer. For laparoscopic radical nephrectomy,
      and recently also for partial nephrectomy, oncological equality with open
      procedures could be demonstrated, with all of the benefits of minimally invasive
      techniques. The use of laparoscopy was one of the most important steps in the
      progress of medicine in the 20th century. Our aims include the further
      improvement of this technique and its distribution to surgical centers.

PMID- 16909276
TI  - Influence of poly(L-lysine) on the structure of
      dipalmitoylphosphatidylglycerol/water dispersions studied by X-ray scattering.
AB  - The interaction between the negatively charged phospholipid DPPG and positively
      charged poly(L: -lysine) (PLL) of different lengths was studied by X-ray
      scattering in the SAXS and WAXS region. As a reference pure DPPG (Na salt) was
      investigated over a wide temperature range (-30 to 70 degrees C). The phase
      behavior of DPPG in aqueous and in buffer/salt dispersions showed a metastable
      subgel phase at low temperatures and a recrystallization upon heating before
      reaching the liquid-crystalline phase. The presence of additional salt stabilizes
      the bilayer structure and decreases the recrystallization temperature. Large
      changes in the SAXS region are not connected with changes in chain packing. In
      DPPG/PLL samples, the PLL is inserted between adjacent headgroup layers and
      liberates counterions which give rise to a freezing point depression. In the
      complex with DPPG PLL form an alpha-helical secondary structure at pH 7 and
      temperatures below the gel to liquid-crystalline phase transition. This prevents
      DPPG from recrystallization and strongly increases the stacking order. The
      lamellar repeat distance is decreased and fixed by the helix conformation of PLL
      in the gel phase. PLL with n = 14 is too short to form helices and is squeezed
      out reversibly from the interbilayer space upon cooling by freezing of trapped
      water. In dispersions with longer PLLs (n > 400) at -20 degrees C a 1D
      crystallization of PLL alpha-helices in the aqueous layer between the headgroups
      takes place. A structural model is presented for the lateral periodic complex,
      which is similar to the known cationic lipid/DNA complex.

PMID- 16909277
TI  - MR imaging of the intraarticular disk of the acromioclavicular joint: a
      comparison with anatomical, histological and in-vivo findings.
AB  - OBJECTIVE: To characterize MRI features of the intraarticular disk of the
      acromioclavicular joint. DESIGN: We studied the appearance of 11
      acromioclavicular joints of six cadavers (subjects aged 57-89 years at the time
      of death) and six healthy shoulders on T1-weighted, T2 (TSE)-weighted, STIR and
      PD (fat saturated) magnetic resonance imaging (MRI) and compared the findings
      with observations during dissection and histological examination. RESULTS:
      Macroscopic examinations showed two wedge-shaped disks underneath the superior
      and above the inferior joint capsule in nine specimens. In two specimens the
      acromioclavicular joints were degenerated. Histologically, the disk tissue
      consisted of fibrocartilage whereas the joint cartilage was partly degenerated,
      containing zones of fibrocartilage amidst degenerated hyaline cartilage, which
      may explain the similar signal intensity of both structures in all sequences
      used. MR appearance of the intraarticular structures of the acromioclavicular
      joint was similar in cadaveric and healthy shoulders. CONCLUSIONS: The
      difficulties related to imaging the acromioclavicular joint may be explained by
      the anatomy. Similar signal intensity of cartilage and disk may be explained by
      their similar histological structure (fibrocartilage). MRI findings should be
      interpreted with respect to the variable anatomy. These results may serve as a
      basis for further radiological studies of the acromioclavicular joint.

PMID- 16909278
TI  - Subcutaneous panniculitis-like T-cell lymphoma: US and CT findings in three
      patients.
AB  - Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare disorder. We
      examined two females and one male with multiple soft-tissue masses in the
      abdominal wall. One of these three patients also had soft-tissue masses in the
      right thigh and right buttock. The histologic diagnosis was revealed as SPTCL in
      all three cases. The ultrasound (US) findings in two of these cases were diffuse,
      ill-defined hyperechoic areas with a linear vascular signal. The findings of the
      abdominal and pelvic computed tomography (CT) scanning with contrast enhancement
      were multiple enhancing nodules with an infiltrative pattern of peripheral
      subcutaneous fat layer in all three cases. We report US and CT findings of SPTCL
      in these three patients.

PMID- 16909280
TI  - A simplified conceptual model of carbon/nitrogen functioning for QTL analysis of
      winter wheat adaptation to nitrogen deficiency.
AB  - Breeding new varieties adapted to low-input agricultural practices is of
      particular interest in light of current economical and environmental concerns.
      Improving nitrogen (N) uptake and N utilization efficiency (NUE) are two ways of
      producing varieties tolerant to low N input. To offer new possibilities to
      breeders, it is necessary to acquire more knowledge about these two processes.
      Knowing C and N metabolisms are linked and knowing N uptake is partly explained
      by root characteristics, we carried out a QTL analysis for traits associated with
      N uptake and NUE by using both a conceptual model of C/N plant functioning and a
      root architecture description. A total of 120 lines were selected according to
      their genotype among 241 doubled haploids derived from two varieties, one N
      stress tolerant and the other N stress sensitive. They were grown in hydroponic
      rhizotrons under N-limited nutritional conditions. Initial conditions varied
      among genotypes; therefore, total root length on day 1 was used to correct
      traits. Heritabilities ranged from 13 to 84%. Thirty-two QTL were located: 6
      associated with root architecture (on chromosomes 4B, 5A, 5D and 7B), 6
      associated with model efficiencies (1B, 2B, 6A, 6B, 7A, 7B and 7D) and 20
      associated with state variables (1A, 1B, 2B, 4B, 5A, 5B and 6B). The effects of
      the dwarfing gene Rht-B1 on root traits are discussed, as well as the features of
      a conceptual plant functioning model, as a useful tool to assess pertinent traits
      for QTL detection. It is suggested that further studies that couple QTL with a
      functioning model and a root architecture description could serve in the search
      for ideotypes.

PMID- 16909279
TI  - Plastid genome characterisation in Brassica and Brassicaceae using a new set of
      nine SSRs.
AB  - We report a new set of nine primer pairs specifically developed for amplification
      of Brassica plastid SSR markers. The wide utility of these markers is
      demonstrated for haplotype identification and detection of polymorphism in B.
      napus, B. nigra, B. oleracea, B. rapa and in related genera Arabidopsis,
      Camelina, Raphanus and Sinapis. Eleven gene regions (ndhB-rps7 spacer, rbcL-accD
      spacer, rpl16 intron, rps16 intron, atpB-rbcL spacer, trnE-trnT spacer, trnL
      intron, trnL-trnF spacer, trnM-atpE spacer, trnR-rpoC2 spacer, ycf3-psaA spacer)
      were sequenced from a range of Brassica and related genera for SSR detection and
      primer design. Other sequences were obtained from GenBank/EMBL. Eight out of nine
      selected SSR loci showed polymorphism when amplified using the new primers and a
      combined analysis detected variation within and between Brassica species, with
      the number of alleles detected per locus ranging from 5 (loci MF-6, MF-1) to 11
      (locus MF-7). The combined SSR data were used in a neighbour-joining analysis
      (SMM, D (DM) distances) to group the samples based on the presence and absence of
      alleles. The analysis was generally able to separate plastid types into taxon
      specific groups. Multi-allelic haplotypes were plotted onto the neighbour joining
      tree. A total number of 28 haplotypes were detected and these differentiated 22
      of the 41 accessions screened from all other accessions. None of these haplotypes
      was shared by more than one species and some were not characteristic of their
      predicted type. We interpret our results with respect to taxon differentiation,
      hybridisation and introgression patterns relating to the 'Triangle of U'.

PMID- 16909281
TI  - Predicted taxonomic patterns in pheromone production by longhorned beetles.
AB  - Males of five species of three tribes in the longhorned beetle subfamily
      Cerambycinae produce volatile pheromones that share a structural motif (hydroxyl
      or carbonyl groups at carbons two and three in straight-chains of six, eight, or
      ten carbons). Pheromone gland pores are present on the prothoraces of males, but
      are absent in females, suggesting that male-specific gland pores could provide a
      convenient morphological indication that a species uses volatile pheromones. In
      this article, we assess the taxonomic distribution of gland pores within the
      Cerambycinae by examining males and females of 65 species in 24 tribes using
      scanning electron microscopy. Gland pores were present in males and absent in
      females of 49 species, but absent in both sexes of the remaining 16 species.
      Pores were confined to indentations in the cuticle. Among the species that had
      male-specific gland pores were four species already known to produce volatile
      compounds consistent with the structural motif. These findings support the
      initial assumption that gland pores are associated with the production of
      pheromones by males. There were apparently no taxonomic patterns in the presence
      of gland pores. These findings suggest that volatile pheromones play an important
      role in reproduction for many species of the Cerambycinae, and that the trait is
      evolutionarily labile.

PMID- 16909282
TI  - On Karl Hadeler becoming 70.

PMID- 16909283
TI  - Locked-in state due to Epstein-Barr virus primary infection in an immunocompetent
      patient.

PMID- 16909284
TI  - Effects of the Sabin-like mutations in domain V of the internal ribosome entry
      segment on translational efficiency of the Coxsackievirus B3.
AB  - The domain V within the internal ribosome entry segment (IRES) of poliovirus (PV)
      is expected to be important in its own neurovirulence because it contains an
      attenuating mutation in each of the Sabin vaccine strains. In this study, we try
      to find out if the results observed in the case of Sabin vaccine strains of PV
      can be extrapolated to another virus belonging to the same genus of enteroviruses
      but with a different tropism. To test this hypothesis, we used the coxsackievirus
      B3 (CVB3), known to be the most common causal agent of viral myocarditis. The
      introduction of the three PV Sabin-like mutations in the equivalent positions
      (nucleotides 484, 485, and 473) to the domain V of the CVB3 IRES results in
      significant reduced viral titer of the Sabin3-like mutant (Sab3-like) but not on
      those of Sab1- and Sab2-like mutants. This low titer was correlated with poor
      translation efficiency in vitro when all mutants were translated in rabbit
      reticulocyte lysates. However, elucidation by biochemical probing of the
      secondary structure of the entire domain V of the IRES of Sabin-like mutants
      reveals no distinct profiles in comparison with the wild-type counterpart.
      Prediction of secondary structure by MFOLD program indicates a structural
      perturbation of the stem containing the Sab3-like mutation, suggesting that
      specific protein-viral RNA interactions are disrupted, preventing efficient viral
      translation.

PMID- 16909285
TI  - Conserved repeats in the kinetoplast maxicircle divergent region of Leishmania
      sp. and Leptomonas seymouri.
AB  - The maxicircle control region [also termed divergent region (DR)] composed of
      various repeat elements remains the most poorly studied part of the kinetoplast
      genome. Only three extensive DR sequences demonstrating no significant similarity
      were available for trypanosomatids (Leishmania tarentolae, Crithidia oncopelti,
      Trypanosoma brucei). Recently, extensive DR sequences have been obtained for
      Leishmania major and Trypanosoma cruzi. In this work we have sequenced DR
      fragments of Leishmania turanica, Leishmania mexicana, Leishmania chagasi and two
      monogenetic trypanosomatids Leptomonas seymouri and Leptomonas collosoma. With
      the emergence of the additional extensive sequences some conserved features of DR
      structure become evident. A conserved palindromic sequence has been revealed in
      the DRs of the studied Leishmania species, L. seymouri, and T. cruzi. The overall
      DR structure appears to be similar in all the Leishmania species, their relative
      L. seymouri, and T. brucei: long relatively GC-rich repeats are interspersed with
      clusters of short AT-rich repeats. C. oncopelti, L. collosoma, and T. cruzi have
      a completely different DR structure. Identification of conserved sequences and
      invariable structural features of the DR may further our understanding of the
      functioning of this important genome fragment.

PMID- 16909286
TI  - Morphological and molecular analyses of ectomycorrhizal diversity in a man-made
      T. melanosporum plantation: description of novel truffle-like morphotypes.
AB  - Below-ground ectomycorrhizal communities are often species-rich, and monitoring
      their dynamics is important to understand the conditions that promote truffle
      fructification. Characterization of the different ectomycorrhizas (ECM) at the
      species level can now be achieved by combining detailed morphological and
      anatomical descriptions with molecular approaches. Following this strategy, we
      have characterized ectomycorrhizal biodiversity in an artificial Tuber
      melanosporum plantation. Although the plantation was unproductive, T.
      melanosporum mycorrhizas were the most present and two Tuber-like mycorrhizal
      morphotypes, named ECMm1 and ECMm3, showing distinctive features were found.
      Internal transcribed spacer (ITS) phylogenetic analysis demonstrated that ECMm3
      is related to the Tuber rufum/Tuber ferrugineum species complex, whereas ECMm1
      shows the highest ITS similarity with Tuber scruposum and fungi-colonizing
      Epipactis roots. The results presented here provide more insights into genetic
      variability, mycorrhizal morphology, and below-ground distribution of fungi
      associated with artificial truffle plantations.

PMID- 16909287
TI  - Arbuscular mycorrhiza alter the concentration of essential oils in oregano
      (Origanum sp., Lamiaceae).
AB  - The effect of root colonization by Glomus mosseae on the qualitative and
      quantitative pattern of essential oils (EO) was determined in three oregano
      genotypes (Origanum sp.). To exclude a simple P-mediated effect through
      mycorrhization the effect of P application to plants on the EO accumulation was
      also tested. In two genotypes the leaf biomass was increased through
      mycorrhization. Root colonization by the arbuscular mycorrhizal fungus (AMF) did
      not have any significant effect on the EO composition in oregano; however, in two
      genotypes the EO concentration significantly increased. As EO levels in P-treated
      plants were not enhanced, we conclude that the EO increase observed in
      mycorrhizal oregano plants is not due to an improved P status in mycorrhizal
      plants, but depends directly on the AMF-oregano plant association.

PMID- 16909288
TI  - Secondary product glycosyltransferases in seeds of Brassica napus.
AB  - This study describes a systematic screen for secondary product UDP
      glycosyltransferases (UGTs; EC 2.4.1) involved in seed development of oilseed
      rape (Brassica napus) and was aimed at identifying genes related to UGT84A9
      encoding UDP-glucose:sinapate glucosyltransferase (EC 2.4.1.120), a proven target
      for molecular breeding approaches to reduce the content of anti-nutritive
      sinapate esters. By RT-PCR with primers recognizing the conserved signature motif
      of UGTs, 13 distinct ESTs could be generated from seed RNA. Sequence analysis
      allowed to assign the isolated ESTs to groups B, D, E, and L of the UGT family.
      In an alternative approach, two open reading frames related to UGT84A9 were
      cloned from the B. napus genome and designated as UGT84A10 and UGT84A11,
      respectively. Functional expression of UGT84A10 revealed that the encoded enzyme
      catalyzes the formation of 1-O-acylglucosides (beta-acetal esters) with several
      hydroxycinnamates whereas, in our hands, the recombinant UGT84A11 did not display
      this enzymatic activity. Semi-quantitative RT-PCR confirmed that the majority of
      potential UGTs specified by the isolated ESTs is differentially expressed. A
      pronounced transcriptional up-regulation during seed development was evident for
      UGT84A9 and one EST (BnGT3) clustering in group E of UGTs. UGT84A10 was highly
      induced in flowers and expressed to a moderate level in late seed maturation
      indicating a possible involvement in seed-specific sinapate ester biosynthesis.

PMID- 16909289
TI  - Actin is bundled in activation-tagged tobacco mutants that tolerate aluminum.
AB  - A panel of aluminum-tolerant (AlRes) mutants was isolated by protoplast-based T
      DNA activation tagging in the tobacco cultivar SR1. The mutants fell into two
      phenotypic classes: a minority of the mutants were fertile and developed
      similarly to the wild type (type I), the majority was male-sterile and grew as
      semi-dwarfs (type II). These traits, along with the aluminum tolerance, were
      inherited in a monogenic dominant manner. Both types of mutants were
      characterized by excessive bundling of actin microfilaments and by a strongly
      increased abundance of actin, a phenotype that could be partially phenocopied in
      the wild type by treatment with aluminum chloride. The actin bundles could be
      dissociated into finer strands by addition of exogenous auxin in both types of
      mutants. However, actin microfilaments and leaf expansion were sensitive to
      blockers of actin assembly in the wild type and in the mutants of type I, whereas
      they were more tolerant in the mutants of type II. The mutants of type II
      displayed a hypertrophic development of vasculature, manifest in form of
      supernumerary leaf veins and extended xylem layers in stems and petioles. Whereas
      mutants of type I were characterized by a normal, but aluminum-tolerant polar
      auxin-transport, auxin-transport was strongly promoted in the mutants of type II.
      The phenotype of these mutants is discussed in terms of reduced endocytosis
      leading, concomitantly with aluminum tolerance, to changes in polar auxin
      transport.

PMID- 16909290
TI  - Thrombosis of the splenoportal axis after splenectomy.
AB  - BACKGROUND AND AIMS: Thrombosis of the portal system is a potentially life
      threatening complication after splenectomy. The reported incidence is low
      (approximately or = 1%), however may be underestimated due to difficult in making
      the diagnosis. The factors associated with its development and the clinical
      outcome are poorly characterized. The aim of this study was to assess the
      incidence, risk factors, treatment, and outcome in series of consecutive cases.
      MATERIALS AND METHODS: All patients who had undergone a splenectomy (both open
      and laparoscopic) between January 1997 and December 2004 at the Department of
      Surgery of University of Milan Bicocca were retrospectively reviewed. Twelve
      cases of thrombosis (7.6%) among 158 splenectomies were identified. No
      significant differences were noted in age, gender, and surgical approach between
      patients who developed thrombosis and those who did not. Indication for
      splenectomy in patients with thrombosis were myeloproliferative disorders (n=5),
      hemolytic disease (n=4), and lymphoproliferative disorder (n=3). All patients had
      splenomegaly (mean 1.380 kg, range 0.400-3.120 kg). RESULTS: Among patients with
      myeloproliferative disorders, five (33%) developed the complication, compared
      with 4 of 35 (11.5%) with hemolytic disease. Patients with both splenic weight
      >2.500 kg and myeloproliferative disorders had 80% incidence of portal
      thrombosis. Preoperative prophylactic anticoagulant therapy with low molecular
      weight heparin was administered in each case. All these patients had fever,
      abdominal pain, or leukocytosis. All diagnoses were made by contrast-enhanced
      computed tomography (CT) scan and ecocolordoppler ultrasonography, and
      anticoagulation therapy was initiated immediately. Treatment within 15 days after
      splenectomy was successful in all patients, while delayed treatment was
      ineffective. CONCLUSIONS: Portal thrombosis should be suspected in patients with
      fever or abdominal pain after splenectomy. Patients with myeloproliferative
      disorders and hemolytic diseases are at higher risk, as well as patients with
      marked splenomegaly. A high index of suspicion, early diagnosis, and prompt
      anticoagulation therapy are the keys to a successful outcome.

PMID- 16909291
TI  - Chronic inflammation and oxidative stress in the genesis and perpetuation of
      cancer: role of lipid peroxidation, DNA damage, and repair.
AB  - BACKGROUND AND AIMS: Chronic inflammation, induced by biological, chemical, and
      physical factors, was associated with increased risk of human cancer at various
      sites. Chronic inflammatory processes induce oxidative/nitrosative stress and
      lipid peroxidation (LPO), thereby generating excess reactive oxygen species
      (ROS), reactive nitrogen species (RNS), and DNA-reactive aldehydes. Miscoding
      etheno- and propano-modified DNA bases are generated inter alia by reaction of
      DNA with these major LPO products. Steady-state levels of LPO-derived (etheno-)
      DNA adducts in organs affected by persistent inflammatory processes were
      investigated as potential lead markers for assessing progression of inflammatory
      cancer-prone diseases. RESULTS: Using ultrasensitive and specific detection
      methods for the analysis of human tissues, cells, and urine, etheno-DNA adduct
      levels were found to be significantly elevated in the affected organs of subjects
      with chronic pancreatitis, ulcerative colitis, and Crohn's disease. Patients with
      alcohol-related liver diseases showed excess hepatic DNA damage progressively
      increasing from hepatitis, fatty liver, to liver cirrhosis. Ethenodeoxyadenosine
      excreted after DNA repair in urine of hepatitis B virus-related chronic hepatitis
      and liver cirrhosis patients was increased up to 90-fold. Putative mechanisms
      that may control DNA damage in inflamed tissues including impaired or imbalanced
      DNA repair pathways are reviewed. CONCLUSION: Persistent oxidative/nitrosative
      stress and excess LPO are induced by inflammatory processes in a self
      perpetuating process and cause progressive accumulation of DNA damage in target
      organs. Together with deregulation of cell homeostasis, the resulting genetic
      changes act as driving force in chronic inflammation-associated human disease
      pathogenesis. Thus steady-state levels of DNA damage caused by ROS, RNS, and LPO
      end products provide promising molecular signatures for risk prediction and
      potential targets and biomarkers for preventive measures.

PMID- 16909292
TI  - Transfusion-related acute lung injury (TRALI)--an important, severe transfusion
      related complication.
AB  - BACKGROUND: Transfusion-related acute lung injury (TRALI) is an immune-mediated
      transfusion reaction that can cause severe complications or even death. It is now
      the leading cause of transfusion-related death in the United States. METHODS: The
      TRALI syndrome is presented in two cases in a surgical intensive care unit and
      discussed against the background of the present literature. In both cases,
      concomitant diseases led to an extremely difficult course of TRALI. CONCLUSIONS:
      Knowledge of the TRALI syndrome is necessary to enable early diagnosis and
      treatment. It should be taken into consideration at any time when cardiopulmonary
      instability occurs after transfusion of blood products, which is a frequent event
      on surgical Intensive Care Units. TRALI remains a clinical diagnosis supported by
      serologic studies if these are available. Against the background of this
      potentially life-threatening complication, every single indication to transfuse
      blood products needs to be scrutinized carefully.

PMID- 16909293
TI  - Infectiological diagnostic problems in tertiary peritonitis.
AB  - BACKGROUND: The tertiary peritonitis causes the highest mortality in
      intraabdominal infections. Surgical interventions and antibiotic therapy may only
      provide an incomplete impact on nosocomial infections acquired at an intensive
      care unit (ICU) [Nathens et al., World J Surg 22:158-163, 28]. To open up new
      resources in the management, in particular, in the previous infectious
      diagnostic, the aim was to investigate the infectious course as well as the
      diagnostic value of laboratory parameters and microbiological monitoring.
      MATERIALS AND METHODS: In this retrospective patient cohort study from the
      Surgical ICU of a University Hospital (capacity, n=12), overall, 60 patients with
      a tertiary peritonitis were enrolled. RESULTS: Approximately 20% of the patients
      with an intraabdominal infection developed a tertiary peritonitis. A tertiary
      peritonitis can more frequently develop in nosocomial intraabdominal infections,
      in particular, in case of necrotizing pancreatitis. The device-associated
      infection rate in the spectrum of nosocomial infections is sevenfold higher than
      in all ICU patients. Compared with the secondary peritonitis, its mortality is
      double as high: 35%. In the diagnostic characterizing the course of the
      nosocomial, prognosis-relevant infections, usual inflammatory parameters show a
      considerable loss of their sensitivity with a range from 35-57%. By the mean of a
      routine microbiological monitoring, 47.3% of the analysed subsequent infections
      could be identified at an early stage. CONCLUSION: In patients with a severe
      infection, an early diagnostic and treatment of infectious "second hits" can
      improve the complication rate and prognosis. During the prolonged and complicated
      septic course of tertiary peritonitis, an additional routine microbiological
      monitoring contributed effectively to early detection and diagnostic of
      nosocomial infections. Further studies to investigate the value and efficacy of
      such monitoring, which have been abandoned, should be undertaken in infectious
      high-risk patients.

PMID- 16909294
TI  - Accuracy of intra-operative PTH measurement during subtotal parathyroidectomy for
      tertiary hyperparathyroidism after renal transplantation.
AB  - BACKGROUND AND AIMS: Intra-operative parathyroid hormone (IOPTH) results are not
      known in the setting of tertiary hyperparathyroidism (HPT) after renal
      transplantation. MATERIALS AND METHODS: A retrospective analysis of 35 tertiary
      HPT patients who all underwent subtotal parathyroidectomy and IOPTH monitoring
      was conducted. RESULTS: The mean follow-up time was 2.2+/-1.4 years. Thirty-four
      patients were cured; one patient (2.8%) had a persistent disease and was cured
      after reoperation. Median parathyroid hormone (PTH) (median percent decrease from
      highest) at baseline and at 5, 10, 20, and 30 min were 244, 78 (69%), 63 (75%),
      53 (79%), and 49 pg/ml (83%), respectively. Four patients who were cured had a
      decrease of <50% at 5 min and two of them had a decrease of <50% at 10 min. The
      patient with persistent disease had a decrease of >50% at 10 min. The sensitivity
      of the test was 94% at 10 min using the Miami criteria. CONCLUSION: This study
      shows that IOPTH in tertiary hyperparathyroidism has a high sensitivity. However,
      because of the low risk of persistent hyperparathyroidism when a subtotal
      parathyroidectomy is performed, its potential impact on the overall success rate
      is very small. We therefore do not recommend the routine use of IOPTH in tertiary
      hyperparathyroidism.

PMID- 16909295
TI  - Laparoscopic management of appendicitis and symptomatic cholelithiasis during
      pregnancy.
AB  - BACKGROUND: Laparoscopic surgery during pregnancy is a challenging procedure that
      most surgeons are reluctant to perform. The objective of this study was to
      evaluate whether laparoscopic appendectomy and cholecystectomy is safe in
      pregnant women. The management of these situations remains controversial. We
      report a single center study describing the successful management of 16 patients
      during pregnancy. METHODS: More than 3,356 laparoscopic procedures were performed
      in our institutions between May 1990 and June 2005. Sixteen of these patients
      were operated on in the second and third trimester between 22 and 32 weeks of
      estimated gestational age. We performed 11 laparoscopic appendectomies and 5
      laparoscopic cholecystectomies. We also reviewed the management and operative
      technique used in these patients. RESULTS: In this study, the laparoscopic
      appendectomy or cholecystectomy was performed successfully in all patients. Three
      patients were in their second trimester, weeks 22, 23, and 25, and 13 were in the
      third trimester, weeks 27 (three patients), 28 (five patients), 31 (three
      patients), and 32 (two patients). No maternal or fetal morbidity occurred. Open
      laparoscopy was performed safely in all patients and all patients delivered
      healthy babies. CONCLUSION: From our experience laparoscopic management of
      appendicitis and biliary colic during pregnancy is safe, however the second
      trimester is preferable for laparoscopic cholecystectomy. Pregnancy is not a
      contraindication to the laparoscopic approach to appendicitis or symptomatic
      cholelithiasis. We believe that laparoscopic operations, when performed by
      experienced surgeons, are safe and even preferable for the mother and the fetus.

PMID- 16909296
TI  - Role of cyclosporin in preventing or delaying colectomy in children with severe
      ulcerative colitis.
AB  - BACKGROUND: Oral cyclosporin (CyA) has been widely and successfully used in adult
      patients with severe ulcerative colitis (UC) to delay or avoid colectomy. AIM: To
      determine if treatment with oral CyA is similarly effective in pediatric patients
      MATERIALS AND METHODS: Data on all patients with severe UC treated with oral CyA
      in our unit were collected retrospectively. Patients were treated with CyA if
      dependent on or resistant to steroids, and therefore, candidates for colectomy.
      RESULTS: Thirty-two patients with severe UC were treated with CyA administered
      orally at a dose needed to obtain therapeutic blood levels (150-250 ng/ml).
      Twenty-eight of 32 patients (87%) had an immediate response within 11 days. Four
      (13%) did not respond and underwent colectomy. One patient had two cycles of
      treatment and is in remission. Two patients underwent three cycles of treatment
      because of relapse, but both eventually underwent elective colectomy. Three other
      patients underwent elective colectomy. A total of nine colectomies were
      performed. CONCLUSIONS: Treatment with oral CyA altered the course of UC in 28/32
      (87%) of patients; 4/32 (13%) did not respond to oral CyA and underwent
      colectomy. Of the 28 patients that responded to CyA, five underwent later
      elective colectomy. Overall, in 72% of patients, colectomy was avoided. We,
      therefore, suggest a trial of oral CyA in all children with severe UC who are
      dependent or resistant to corticosteroids.

PMID- 16909297
TI  - Arthroscopic interpositional arthroplasty for Freiberg's disease.
AB  - Freiberg's disease is a relatively rare condition and can be difficult to manage,
      especially in those with late stages. Surgical treatment should be considered if
      conservative treatment cannot relieve the symptoms. We describe an arthroscopic
      interpositional arthroplasty for extensive late stages (stage IV or V) Freiberg's
      disease. Metatarsophalangeal arthroscopy is performed with dorsolateral and
      dorsomedial portals. Loose body is removed and joint surfaces are debrided.
      Extensor digitorum brevis tendon graft is harvested and rolled and brought into
      the joint. The technique is easy and can be performed on outpatient basis.

PMID- 16909298
TI  - Modified Prusik knot versus whipstitch technique for soft tissue fixation in
      anterior cruciate ligament reconstruction: a biomechanical analysis.
AB  - Appropriate graft tension and secure graft incorporation in bone tunnels are
      essential for successful anterior cruciate ligament (ACL) reconstruction using
      hamstring tendon autografts. Permanent viscoplastic elongation in response to
      cyclic loading in the early postoperative period and the interposition of suture
      material in the tendon-bone interface might negatively affect graft function and
      rigid graft incorporation in the bone tunnels. A modified Prusik knot is an
      alternative option to the commonly used whipstitch technique for soft tissue
      fixation in ACL reconstruction. This is a controlled laboratory study. Sixteen
      formalin-fixed human cadaver semitendinosus tendons were armed with a modified
      Prusik knot or a whipstitch and tested in a load-to-failure test with a constant
      displacement rate of 1 mm/s, 14 in the cyclic loading test with 100 cycles from
      10 to 50 N followed by 100 cycles from 10 to 75 N. The modified Prusik knot
      showed smaller force-induced displacements and higher stiffness of the entire
      construct in the load-to-failure test. Smaller preconditioning displacements were
      the only significant differences in the cyclic loading test. The modified Prusik
      knot has equal or superior mechanical properties and provides a larger area in
      the tendon-bone interface without suture material compared with the whipstitch
      technique.

PMID- 16909299
TI  - The anatomy of the proximal tibia in pediatric and adolescent patients:
      implications for ACL reconstruction and prevention of physeal arrest.
AB  - Although the treatment of anterior cruciate ligament (ACL) tears in skeletally
      immature patients is still controversial, several studies have advocated ACL
      reconstruction in selected patients to prevent secondary injury. The proximal
      tibial physis is a structure at risk during ACL reconstruction in young patients,
      and physeal growth complications have been reported after surgery in this area.
      The relationship between the ACL and the proximal tibial physeal/apophyseal
      regions is poorly understood. This study examined the MRI anatomy of the ACL and
      the proximal tibia apophysis and epiphysis. MRIs of 59 skeletally immature knees
      were reviewed (Average age = 12.75 years, range 6-15) to define the anatomy of
      the epiphyseal and apophyseal regions. Measurements were recorded in three
      parasagittal planes: (1) at the lateral border of the patellar tendon, (2) the
      lateral edge of the ACL insertion, and (3) the medial edge of the ACL insertion.
      A single three-dimensional (3D) computed tomography (CT) scan was used to
      evaluate the position of standard drill holes used in ACL reconstruction to
      assess for potential degree of injury to the epiphyseal and apophyseal growth
      plates. In the parasagittal planes, the average height of the epiphysis was 19.6,
      20.7, and 21.5 mm at the lateral border of the patellar tendon, the lateral
      border of the ACL, and the medial border of the ACL, respectively. At the level
      of the same landmarks, the apophysis extended below the physis at an average of
      20.2, 16.8, and 7.0 mm, respectively. Expressed as a percentage of epiphysis
      height this was an average of 104, 82, and 33%, respectively. Examination of 3D
      CT images revealed that variations in drill hole placement had effects on the
      volume of injury to the proximal tibial physis and apophysis. Drill holes that
      started more medial, distal, and with a steeper angle of inclination reduced the
      amount of physis and apophysis violated when compared with holes placed more
      lateral, proximal, and with a shallow angle of inclination. The proximal tibial
      physis and apophysis is vulnerable to injury by drill hole placement during ACL
      reconstruction in skeletally immature patients. This paper defines the anatomic
      relationship of the apophyseal and epiphyseal regions of the physis in the
      proximal tibia. The volume of injury to the physis can be reduced by avoiding
      tunnel placement that is too lateral or too proximal on the tibia. A better
      understanding of these relationships may guide the placement of tibial drill
      holes, which have a lower risk of producing significant physeal damage.

PMID- 16909300
TI  - Asymmetrical total knee arthroplasty does not improve patella tracking: a study
      without patella resurfacing.
AB  - It is often suggested that patella tracking after total knee arthroplasty (TKA)
      with an asymmetrical patella groove is more physiological than with a symmetrical
      patella groove. Therefore, this study tried to address two questions: what is the
      effect of TKA on patella tracking, and is patella tracking after asymmetrical TKA
      more physiological than patella tracking after symmetrical TKA? The patellar and
      tibial kinematics of five cadaveric knee specimens were measured in the intact
      situation, after the incision and suturing of a zipper, and after placement of a
      symmetrical TKA and an asymmetrical TKA, respectively. The patellae were not
      resurfaced. The flexion-extension kinematics were measured with an internal and
      external tibial moment to determine the envelope of motion (laxity bandwidth) of
      the tibio-femoral and patello-femoral articulation. The kinematics after TKA
      showed statistically significant changes in comparison to the intact situation:
      patellar medio-lateral translation, patellar tilt and tibial rotation were
      significantly affected. No statistically significant differences in knee
      kinematics were found between the symmetrical and the asymmetrical TKAs. We
      conclude that conventional TKA significantly changes physiological patello
      femoral kinematics, and TKA with an asymmetrical patella groove does not improve
      the non-physiological tracking of the patella.

PMID- 16909301
TI  - Prospective and randomized evaluation of ACL reconstruction with three
      techniques: a clinical and radiographic evaluation at 5 years follow-up.
AB  - A variety of graft sources have been used for ACL reconstruction to improve
      functions and kinematics in ACL deficient knees. The two most commonly used
      autogenous grafts are the central third of the patellar tendon and the hamstring
      tendon constructs. The choice of different grafts and different construct
      influence the final clinical outcome of ACL reconstruction. The 3 groups, of 25
      patients each, were generated by choosing the technique (PT tendon, 4 strand
      hamstring, and single hamstring plus extraarticular plasty) to utilize and
      followed for 5 years, with an alternate systematic sampling. Our comparison has
      shown significant kneeling pain in the patellar tendon with respect to the groups
      with hamstrings techniques. Single hamstring plus extraarticular plasty achieved
      subjective score significantly higher with respect to the other two groups as
      well as for the time to resume sport. The study confirms that patellar tendon and
      hamstring can be equivalent options for ACL reconstruction. This study
      demonstrated that a superior outcome as far as subjective clinical findings were
      concerned, was obtained in group III. Patients in the latter group were also able
      to return to sports sooner than those in the bone-patellar tendon graft group and
      the four-strand hamstring group.

PMID- 16909302
TI  - Traumatic separation of an uncommon bipartite patella type: a case report.
AB  - The authors report about a case of traumatic separation of a horizontally
      bipartite patella in a young female soccer player. Unspecific anterior knee pain
      preceded the fracture, which had occurred after an inadequate trauma. Open
      reduction and osteosynthesis led to bony union with an excellent clinical outcome
      at follow-up.

PMID- 16909303
TI  - Increased glucose oxidation in H-FABP null soleus muscle is associated with
      defective triacylglycerol accumulation and mobilization, but not with the defect
      of exogenous fatty acid oxidation.
AB  - Heart-type fatty acid-binding protein (H-FABP) is a major fatty acid-binding
      factor in skeletal muscles. Genetic lack of H-FABP severely impairs the
      esterification and oxidation of exogenous fatty acids in soleus muscles isolated
      from chow-fed mice (CHOW-solei) and high fat diet-fed mice (HFD-solei), and
      prevents the HFD-induced accumulation of muscle triacylglycerols (TAGs). Here, we
      examined the impact of H-FABP deficiency on the relationship between fatty acid
      utilization and glucose oxidation. Glucose oxidation was measured in isolated
      soleus muscles in the presence or absence of 1 mM palmitate (simple protocol) or
      in the absence of fatty acid after preincubation with 1 mM palmitate (complex
      protocol). With the simple protocol, the mutation slightly reduced glucose
      oxidation in CHOW-muscles, but markedly increased it in HFD-muscles;
      unexpectedly, this pattern was not altered by the addition of palmitate, which
      reduced glucose oxidation in both CHOW- and HFD-solei irrespective of the
      mutation. In the complex protocol, the mutation first inhibited the synthesis and
      accumulation of TAGs and then their mobilization; with this protocol, the
      mutation increased glucose oxidation in both CHOW- and HFD-solei. We conclude:
      (i) H-FABP mediates a non-acute inhibition of muscle glucose oxidation by fatty
      acids, likely by enabling both the accumulation and mobilization of a critical
      mass of muscle TAGs; (ii) H-FABP does not mediate the acute inhibitory effect of
      extracellular fatty acids on muscle glucose oxidation; (iii) H-FABP affects
      muscle glucose oxidation in opposing ways, with inhibition prevailing at high
      muscle TAG contents.

PMID- 16909304
TI  - Rhythmic clock gene expression in heart, kidney and some brain nuclei involved in
      blood pressure control in hypertensive TGR(mREN-2)27 rats.
AB  - Hypertensive TGR(mREN-2)27 rats exerting inverted blood pressure (BP) profile
      were used to study clock gene expression in structures responsible for BP
      control. TGR and control Sprague Dawley male rats were synchronized to the
      light:dark cycle 12:12 with food and water ad libitum. Daily rhythm in per2,
      bmal1, clock and dbp expression in the suprachiasmatic nucleus (SCN), rostral
      ventrolateral medulla (RVLM), nucleus of the solitary tract (NTS), heart and
      kidney was determined in both groups. Sampling occurred in regular 4 h intervals
      when rats of both strains were 11-weeks-old. Blood pressure and relative heart
      weight were significantly elevated in TGR rats in comparison with control.
      Expression of bmal1 and clock was up regulated in SCN of TGR rats but daily
      rhythm in per2 and dbp expression was similar in both groups. Mesor of per2
      expression in RVLM was significantly higher in TGR than in control rats. In NTS
      of TGR rats expression of per2 was phase delayed by 3.5 h in comparison with
      control and bmal1 did not exert rhythmic pattern. Our study provided the first
      evidence about modified function of central and peripheral circadian oscillators
      in TGR rats at the level of clock gene expression. Expression of clock genes
      exerted up regulation in SCN and RVLM and down regulation in NTS. Circadian
      oscillators in selected brain structures were influenced more than oscillators in
      the heart and kidney by additional renin gene. Interactions of RAS and circadian
      system probably contribute to the development of inverted BP profile in TGR rats.

PMID- 16909305
TI  - Ribavirin enhances osteoclast formation through osteoblasts via up-regulation of
      TRANCE/RANKL.
AB  - Hepatitis C combination therapy comprising ribavirin and interferon-alpha causes
      dramatic improvement with the sustained virological response; however, this
      treatment may result in the loss of bone mineral density. To investigate the
      effects of ribavirin on bone cells, we examined osteoblast differentiation as
      well as the formation of osteoclasts from their precursors. Ribavirin enhances
      osteoclast formation through osteoblasts by up-regulation of TRANCE/RANKL gene
      expression, whereas it has no significant effect on either osteoblast
      differentiation or on bone formation. Understanding ribavirin's underlying
      mechanism of action on bone cells will enable the improved management of bone
      loss in chronic hepatitis C patients.

PMID- 16909306
TI  - Divergent signaling pathways mediate induction of Na,K-ATPase alpha1 and beta1
      subunit gene transcription by low potassium.
AB  - Prolonged inhibition of Na,K-ATPase enzymatic activity by exposure of a variety
      of mammalian cells to low external K+ yields a subsequent adaptive up-regulation
      of Na,K-ATPase expression. The aim of this study was to examine the intracellular
      signal transduction system that is responsible for mediating increased Na,K
      ATPase subunit gene expression in primary cultures of neonatal rat cardiac
      myocytes. In this work, we show long-term inhibition of Na,K-ATPase function with
      0.6 mM K+ resulted in hypertrophy of cardiac myocytes and augmentation of Na,K
      ATPase alpha1 and beta1 subunit gene expression. Transient transfection
      experiments in neonatal rat cardiac myocytes demonstrated that low K+ induction
      of alpha1 and beta1 gene transcription was dependent on intracellular Ca2+ and
      activation of calcineurin. Based on effects of pharmacological inhibitors,
      protein kinase A (PKA), extracellular signal-regulated kinase 1/2 (ERK1/2) and
      histone deacetylase were found to be unique downstream components in the low K+
      signal transduction pathway leading to increased alpha1 subunit promoter
      activity. Similarly, low K+-induced beta1 subunit gene transcription was
      dependent on activation of protein kinase C (PKC), c-Jun-N-terminal kinase (JNK)
      and p38 mitogen-activated protein kinase (MAPK). These findings indicate that
      persistent inhibition of Na,K-ATPase activity with low external K+ activates
      overlapping and Na,K-ATPase subunit gene-specific signaling pathways in cardiac
      myocytes.

PMID- 16909307
TI  - In Vivo beta-adrenergic activation of atrial natriuretic factor (ANF) reporter
      expression.
AB  - Isoproterenol (ISO) infusion increases ANF-mRNA levels and control of ANF
      expression lies at the level of transcription. In neonatal cardiomyocytes,
      previous investigations determined that the -125 to -100 region of the rat ANF 5'
      flanking region contained cis-elements critical for control of ISO induced ANF
      transcription. However, it is unclear if these same cis-elements regulate ANF
      transcription in vivo. To examine this question, reporter plasmids containing the
      ANF 5' flanking/promoter region were injected directly into the left ventricle.
      Following a recovery period, osmotic pumps were implanted to infuse vehicle or
      ISO (0.2 or 2.0 mg/kg/d). ISO significantly (p < .05) increased the LV/BW ratio
      in a dose dependent, but not a time dependent manner. ISO significantly (p < .05)
      increased ANF reporter expression in both a dose-dependent and time dependent
      manner. Injections into the midwall of the LV or into the apex did not lead to
      significant differences in ISO-induced ANF reporter expression. Using site
      specific mutations of ANF reporter constructs, comparisons were made of ISO
      induced ANF transcription in vitro in neonatal cardiomyocytes and in vivo in the
      adult heart. Cis-elements critical for ISO activation in cultured cardiomyocytes
      were not essential for the increased expression of the ANF reporters in vivo. The
      results indicate that distinct differences in ANF transcriptional regulation
      exist in vivo in the adult heart as compared with neonatal cardiomyocytes, and
      suggest the recruitment of other signaling pathways beyond adrenergic-receptor
      mediated pathways.

PMID- 16909308
TI  - Requirement for pre-existing of p21 to prevent doxorubicin-induced apoptosis
      through inhibition of caspase-3 activation.
AB  - Doxorubicin (DOX)-induced apoptosis is suppressed by p21 (waf1/cip1/sdi1), a
      cyclin dependent kinase (CDK) inhibitor. Here we show that exogenous expression
      of p21 before, but not after, the DOX-treatment protected p21-deficient human
      colorectal cancer cell line DLD1 from DOX-induced apoptosis. In previous work, we
      demonstrated that p21 inhibits DOX-induced apoptosis via its CDK-binding and CDK
      inhibitory activity. Here we report that pre-existing p21 can associate with pro
      caspase-3 and inhibit caspase-3 activation in the cells, which was at least in
      part responsible for enhancing survival of DOX-treated cells. Furthermore, the N
      terminal domain of p21 was found to interact with pro-caspase-3 in DLD1 cells.
      Thus, we propose that pre-existing p21 is required to prevent DOX-induced
      apoptosis.

PMID- 16909309
TI  - Effect of tri-o-cresyl phosphate on cytoskeleton in human neuroblastoma SK-N-SH
      cell.
AB  - Cytoskeletal components play an important role in maintaining cellular
      architecture and internal organization, with clear involvement of defining cell
      shape, in cell division and other cellular processes, such as neurite extension
      and maintenance. Alterations of cytoskeleton in human neuroblastoma SK-N-SH cells
      after exposure to different concentrations of tri-ocresyl phosphate (TOCP) for 12
      hr were investigated. TOCP decreased the cell viability in a dose-dependent
      manner; the viability of SK-N-SH was reduced to approximately 50% of baseline
      after a 12-hour exposure to TOCP at high concentration (5 mM). Biochemical
      characterization by western blotting revealed that 1 and 5 mM concentrations of
      TOCP significantly inhibited the expression of neurofilament high molecular
      weight protein (NF-H), and that 5 mM TOCP inhibited expression of microtubule
      associated protein 2c and tau protein, but not beta-actin. Indirect
      immunofluorescence analysis revealed that higher concentrations of TOCP decreased
      the length of neuritis and changed the structure of microfilaments, which are
      associated with NF-H. In addition, activities of neuropathy target esterase and
      acetylcholinesterase were significantly reduced after exposure to 5 mM TOCP for
      12 hr. Together, these results suggested that the loss of cytoskeletal components
      is the early event during the process of TOCP toxicity towards human
      neuroblastoma SK-N-SH cells.

PMID- 16909310
TI  - Effect of oxidation of alphaA- and alphaB-crystallins on their structure,
      oligomerization and chaperone function.
AB  - The purpose of this study was to investigate the effect of metal-catalyzed
      oxidation by H(2)O(2) on the structure, oligomerization, and chaperone function
      of alphaA- and alphaB-crystallins. Recombinant alphaA-and alphaB-crystallins were
      prepared by expressing them in E. coli and purifying by size-exclusion
      chromatography. They were incubated with 1.5 mM H(2)O(2) and 0.1 mM FeCl(3) at 37
      ( composite function)C for 24 hrs and the reaction was stopped by adding
      catalase. Structural changes due to oxidation were ascertained by circular
      dichroism (CD) measurements and chaperone activity was assayed with alcohol
      dehydrogenase (ADH) and insulin as target proteins. The oligomeric nature of the
      oxidized proteins was assessed by molecular sieve HPLC. The secondary structure
      of the oxidized alphaA- and alphaB-crystallins has been substantially altered due
      to significant increase in random coils, in addition to decrease in beta-sheet or
      alpha-helix contents. The tertiary structure also showed significant changes
      indicative of different mode of folding of the secondary structural elements.
      Chaperone function was significantly compromised as supported by nearly 50% loss
      in chaperone activity. Oxidation also resulted in the formation of higher
      molecular weight (HMW) proteins as well as lower molecular weight (LMW) proteins.
      Thus, oxidation leads to disintegration of the oligomeric structure of alphaA-
      and alphaB-crystallins. Chaperone activity of the HMW fraction is normal whereas
      the LMW fraction lacks any chaperone activity. So, it appears that the formation
      of the LMW proteins is the primary cause of the chaperone activity loss due to
      oxidation.

PMID- 16909311
TI  - Spatial working memory deficits in autism.
AB  - Previous studies have reported working memory deficits in autism, but this
      finding has been inconsistent. One possibility is that deficits in this domain
      may be present only when working memory load exceeds some limited capacity. High
      functioning individuals with autism performed the CANTAB computerized test of
      spatial working memory. Individuals with autism made more errors than a matched
      group of typically developing controls on this task, and were less likely to
      consistently use a specific organized search strategy to complete the task.
      Overall, these results demonstrate reduced spatial working memory abilities in
      autism, and extend previous findings by demonstrating that these deficits are
      significant when tasks impose heavier demands on working memory.

PMID- 16909312
TI  - Regression versus no regression in the autistic disorder: developmental
      trajectories.
AB  - Developmental regression is a complex phenomenon which occurs in 20-49% of the
      autistic population. Aim of the study was to assess possible differences in the
      development of regressed and non-regressed autistic preschoolers. We
      longitudinally studied 40 autistic children (18 regressed, 22 non-regressed) aged
      2-6 years. The following developmental areas were considered fundamental in the
      first years of life, and were assessed at ages 2, 3, 4, 5, and 6: receptive and
      expressive language, communicative and request modalities, play activities, and
      mental age. Children who regressed showed lower mean performances than those who
      did not regress and, in the time intervals considered, non-regressed children
      improved their ratings in the above mentioned variables significantly more than
      regressed children.

PMID- 16909313
TI  - Energy metabolic changes in the early post-injury period following traumatic
      brain injury in rats.
AB  - Impaired cerebral energy metabolism may be a major contributor to the secondary
      injury cascade that occurs following traumatic brain injury (TBI). To estimate
      the cortical energy metabolic state following mild and severe controlled cortical
      contusion (CCC) TBI in rats, ipsi-and contralateral cortical tissues were frozen
      in situ at 15 and 40 min post-injury and adenylate (ATP, ADP, AMP) levels were
      analyzed using high-performance liquid chromatography (HPLC) and the energy
      charge (EC) was calculated. At 15 min post-injury, mildly brain-injured animals
      showed a 43% decrease in cortical ATP levels and a 2.4-fold increase in AMP
      levels (P < 0.05), and there was a significant reduction of the ipsilateral
      cortical EC when compared to sham-injured animals (P < 0.05). At 40 min post
      injury, the ipsilateral adenylate levels and EC had recovered to the values
      observed in the sham-injury group. In the severe CCC group, there was a 51%
      decrease in ipsilateral cortical ATP levels and a 5.3-fold increase in AMP levels
      with a significant reduction of cortical EC at 15 min post-injury (P < 0.05). At
      40 min post-injury, a 2.6-fold ipsilateral increase in AMP levels and an 11% and
      44% decrease in EC and ATP levels, respectively, remained (P < 0.05). A 37-38%
      reduction of the total adenylate pool was observed ipsilaterally in both CCC
      severity groups at the early time-point, and a 19% and 28% decrease remained in
      the mild and severe CCC groups, respectively, at 40 min post-injury. Significant
      contralateral ATP and EC changes were only observed in the severe CCC group at 40
      min post-injury (P < 0.05). The energy-requiring secondary injury cascades that
      occur early post-injury do not challenge the brain tissue to the extent of ATP
      depletion and may provide a window of opportunity for therapeutic intervention.

PMID- 16909314
TI  - The effects of glutamate and GABA receptor antagonists on nicotine-induced
      neurotransmitter changes in cognitive areas.
AB  - In the present study, we tested the effects of glutamate and GABA receptor
      antagonists on nicotine-induced neurotransmitter changes in the hippocampal
      (dorsal and ventral) and cortical (medial temporal and prefrontal) brain areas of
      conscious freely moving rats via microdialysis. Both the antagonists and nicotine
      were administered intracerebrally. The antagonists tested were NMDA, AMPA
      kainate, and metabotropic glutamate receptor subtype antagonists (MK801, CNQX,
      and LY 341495, respectively) and GABA(A) and GABA(B) receptor subtype antagonists
      (bicuculline and hydroxysaclofen, respectively). We assayed nicotine-induced
      changes in dopamine (DA), norepinephrine (NE), serotonin (5-HT), and their
      metabolites. We found with the antagonists, both decreases and increases in
      nicotine-induced neurotransmitter responses. In the presence of nicotine all the
      antagonists (except LY 341495) caused a decrease in DA levels in the regions
      tested. NE levels were decreased in the cortex by all antagonists. In the
      hippocampus, GABA antagonists decreased NE levels, as did the metabotropic
      glutamate antagonist, LY 341495, while the other glutamate antagonists increased
      NE levels. The results of the 5-HT assay were more variable and dependent on the
      region and antagonist examined; increases were found slightly more often than
      decreases. The changes in metabolites were not often parallel with changes in
      their associated neurotransmitters, indicating that the antagonists also affect
      the metabolism of the neurotransmitters. The effect of the antagonists in the
      absence of nicotine was mostly to decrease the level of neurotransmitters,
      although increases were seen in a few cases. The results suggest that the
      excitatory glutamatergic- and inhibitory GABAergic-amino acid receptors are both
      involved in mediating nicotine-induced neurotransmitter responses, and their
      inhibitory or stimulatory effects are receptor subtype and brain region
      dependent.

PMID- 16909315
TI  - Catheter ablation of atrial fibrillation: a treatment frontier.

PMID- 16909316
TI  - Building interdisciplinary/intersectoral research partnerships for community
      based mental health research with older minority adults.
AB  - Community-based research often brings investigators from different disciplinary
      backgrounds together with community representatives to conduct research on topics
      of mutual concern. This paper describes a case example that illustrates an
      interdisciplinary/intersectoral study of depression and barriers to mental health
      care among older adults and illustrate the factors central to implementing a
      successful research partnership. It will address the following conditions that
      facilitate and challenge interdisciplinary/intersectoral research: (1) achieving
      commonality of purpose in study design and research and referral approaches; (2)
      ensuring the ability to develop, field-test and implement psychometrically
      rigorous and culturally and qualitatively appropriate instruments; (3) building
      effective management structures for interdisciplinary/intersectoral research
      partnerships; and (4) identifying, training and supporting qualified researchers
      to carry out a mental health study with older ethnically diverse adults. The
      paper concludes with strengths and limitations of the approach.

PMID- 16909317
TI  - A retrospective study of childhood gender-atypical behavior in Samoan fa'afafine.
AB  - Retrospective studies, mostly conducted in Western cultures, indicate that
      childhood cross-gender behaviors are strongly predictive of androphilia in adult
      men. To test the cross-cultural validity of these findings, we conducted a study
      of fa'afafine in Independent Samoa. Fa'afafine are a heterogeneous group of
      androphilic males, some of whom are unremarkably masculine, but most of whom
      behave in a feminine manner in adulthood. A total of 53 fa'afafine, 27 control
      men, and 24 control women participated. Participants were asked how often they
      engaged in female- and male-typical behaviors in childhood. Results demonstrated
      that fa'afafine and women recalled engaging in significantly more female-typical
      behaviors and significantly fewer male-typical behaviors in childhood compared to
      the men. Fa'afafine's recalled female-typical and male-typical behaviors did not
      differ significantly from those of women. These results suggest that the
      relationship in males between gender-atypical behavior in childhood and adult
      androphilia is not unique to Western societies and may be a cross-culturally
      universal pattern of psychosexual development shared by most males who are
      predominantly androphilic.

PMID- 16909318
TI  - Emotions during sexual activity: differences between sexually functional and
      dysfunctional men and women.
AB  - The present study investigated the differences in emotional response to automatic
      thoughts presented during sexual activity between sexually functional and
      dysfunctional men and women. A total of 376 participants (160 women and 120 men
      without sexual problems and 47 women and 49 men with a DSM-IV-TR diagnosis of
      sexual dysfunction) completed the Sexual Modes Questionnaire (SMQ male and female
      versions; P. J. Nobre & J. Pinto-Gouveia, 2000) and measures of sexual
      functioning: The International Index of Sexual Function (IIEF; R. C. Rosen et
      al., 1997), and The Female Sexual Function Index (FSFI; R. C. Rosen et al.,
      2000). The SMQ is a combined measure constituted by three interdependent
      subscales: Automatic Thought subscale (AT), Emotional Response subscale (ER), and
      Sexual Response subscale (SR). Emotions were assessed by the ER subscale, where
      participants endorsed emotional reactions (worry, sadness, disillusion, fear,
      guilt, shame, anger, hurt, pleasure, satisfaction) to a list of automatic
      thoughts (AT subscale) that may occur during sexual activity. Results showed that
      both men and women with sexual dysfunction had significantly less positive
      emotional reactions to automatic thoughts during sexual activity. Sexually
      dysfunctional men had significantly more emotions of sadness, disillusion, and
      fear, and less pleasure and satisfaction, compared to men without sexual
      problems. Women with sexual dysfunction had significantly less pleasure and
      satisfaction, and more sadness, disillusion, guilt, and anger. Findings were
      congruent with recent studies indicating that emotions related to depressed
      affect (sadness, disillusion, lack of pleasure) as opposed to negative emotions
      (mostly related to anxiety) were stronger correlates of sexual dysfunction.

PMID- 16909319
TI  - Positive and negative cognitions of sexual submission: relationship to sexual
      violence.
AB  - This study investigated gender differences in cognitions of sexual submission as
      well as their association with sexual violence. Participants were 292
      heterosexual undergraduate students who completed a 56-item checklist assessing
      positive and negative sexual cognitions; they also completed measures assessing
      experiences of sexual abuse in childhood, experiences of sexual coercion in
      adulthood, and use of sexual coercion. Two 10-item sexual submission subscales
      were developed from the checklist. One reflected how often respondents had
      experienced the sexual submission items as positive. The other reflected how
      often these items were experienced as negative. When overall frequency of sexual
      cognitions was controlled, compared to the men, the women reported a
      significantly greater frequency of both positive and negative cognitions of
      sexual submission. Submission cognitions were more often negative for women and
      were more often positive for men. Men and women who had experienced sexual abuse
      in childhood reported more frequent positive sexual submission cognitions but not
      more negative sexual submission cognitions. Conversely, men and women who had
      experienced sexual coercion in adulthood reported more frequent negative sexual
      submission cognitions but not more positive sexual submission cognitions. Having
      used sexual coercion was associated with more frequent positive cognitions of
      sexual submission for both men and women. Implications for the proposed links
      between sexual violence and preferences for cognitions of sexual submission are
      discussed.

PMID- 16909320
TI  - Sexual risk behavior of HIV-positive methamphetamine-using men who have sex with
      men: the role of partner serostatus and partner type.
AB  - This study examined the role of partner serostatus and partner type in relation
      to the sexual risk behaviors and disclosure practices of HIV-positive
      methamphetamine (meth)-using men who have sex with men (MSM). The sample
      consisted of 132 HIV-positive meth-using MSM who reported having both
      serodiscordant (i.e., HIV-negative and unknown serostatus) and seroconcordant
      (i.e., HIV-positive) partners. HIV-positive meth-using MSM engaged in
      significantly fewer acts of anal sex with serodiscordant partners as compared to
      seroconcordant partners. However, mean levels of unprotected anal and oral sex
      were high, and mean levels of protected sex were low for both seroconcordant and
      serodiscordant partners. Oral sex was practiced twice as often as anal sex;
      however, both types of sex were primarily unprotected. This pattern of risky
      sexual behavior was reported for steady, casual, and anonymous partners,
      regardless of partner serostatus. Despite high rates of unprotected sex, rates of
      HIV serostatus disclosure were consistently high for HIV-positive and HIV
      negative steady, casual, and anonymous partners. However, rates of disclosure to
      unknown serostatus partners were low, particularly in relation to anonymous
      partners. Future research should address the reasons why HIV-positive meth-using
      MSM engage in risky sexual activity with serodiscordant partners, and HIV
      prevention programs for this population should emphasize the risks associated
      with unprotected sex with seroconcordant partners.

PMID- 16909321
TI  - Diminished sexual activity, interest, and feelings of attractiveness among HIV
      infected women in two eras of the AIDS epidemic.
AB  - Despite the high prevalence of sexual inactivity, decreased sexual desire, and
      poor sexual satisfaction documented among HIV-infected individuals, women's
      experiences of sexuality following HIV-infection and their reasons for these
      sexual changes remain little examined. Further, the potential effects of the
      availability of highly active antiretroviral therapy (HAART) medications on their
      sexuality have not been explored among women living with HIV/AIDS. To examine
      these issues, focused interviews were conducted with two samples of women living
      with HIV/AIDS: one before the advent of HAART and a second matched sample
      interviewed after HAART became widely available. Women in both the pre-HAART and
      HAART eras frequently discussed decreased sexual activity, a loss of sexual
      interest, and a diminished sense of sexual attractiveness following their HIV
      infection. In addition, they reported a number of reasons for why they had
      discontinued sexual activity or were no longer interested in sex, including
      anxiety about HIV transmission, a loss of freedom and spontaneity during sex,
      fears of emotional hurt, not wanting the hassle of sexual relationships, a loss
      of sexual interest, and a diminished sense of sexual attractiveness. However, the
      types of changes in their sexuality women described, nor the reasons offered for
      these changes, did not differ between women in the pre-HAART and HAART eras. The
      findings suggest that therapeutic intervention may be needed by some HIV-infected
      women to overcome difficulties in resuming healthy sexual relationships following
      their HIV diagnosis and offer insights into the potential content of such
      intervention efforts.

PMID- 16909322
TI  - Having the best intentions is necessary but not sufficient: what would increase
      the efficacy of home visiting for preventing second teen pregnancies?
AB  - OBJECTIVE: Identify ways to increase the impact a well-known home-based
      intervention--the Nurse Family Partnership (NFP)--has on conception rates among
      teenage mothers. METHODS: Secondary analysis of data collected on 111, 13-to-19
      years old, primiparas who were visited in their homes by nurses during, and for 2
      years after pregnancy. Data bearing on assistance with family and career planning
      were culled from the nurses' records. These were graded on a 3-point scale.
      Higher scores reflected more active, therapeutic interventions. The primary
      outcome was repeat pregnancy. RESULTS: The pregnancy rate at 6, 12, and 24 months
      was 8.3%, 18.4%, and 28.1%. Teenagers who conceived were less likely to have used
      contraceptives during the previous six months than those who did not. Almost
      everyone received the recommended number of visits. However, discussions and
      active interventions related to lapses in contraceptive use were only documented
      during 30% of visits. Those who conceived had as many visits and discussions of
      this type as those who did not. Nurses rarely involved boyfriends and family.
      Other differences between teens that did and did not conceive support the NFP
      theoretical framework. CONCLUSIONS: Contrary to the stated aims of the
      intervention, the nurses rarely documented therapeutic interventions that could
      make repeated childbearing fit less harmoniously into the teenagers' lives. The
      best way to strengthen the impact of this program on teen pregnancy rates is to
      deepen the nurses' training so that they are able to intervene actively enough to
      bring about behavioral change in family planning.

PMID- 16909323
TI  - Co-location of health care for adults with serious mental illness and HIV
      infection.
AB  - This study describes persons with serious mental illness and comorbid HIV
      infection and examines the effect of co-location of mental health and HIV care on
      satisfaction, service utilization, and appropriateness of care. One hundred and
      eighteen subjects completed interviews and gave blood samples; medical records
      were abstracted. Most reported few barriers to care and satisfaction with mental
      health and HIV treatment. Co-location of mental health and HIV care did not
      influence satisfaction with care, utilization of services, or appropriateness of
      care. This report challenges the notion that persons with serious mental
      illnesses receive inadequate health care and that they have minimal capacity for
      illness management. These subjects may be benefiting from increased funding for,
      and attention to, persons with HIV infection.

PMID- 16909324
TI  - Correlates and predictors of women's sex trading over time among a sample of out
      of-treatment drugs abusers.
AB  - This research addressed two research questions: (a) controlling for crack use,
      what are the factors associated with women's engagement in ever having traded
      sex? and (b) controlling for crack use, what are the factors associated with
      women's engagement in sex trading in the past 90 days? The sample included 149
      sexually active, crack using women selected from a subsample of participants in
      the Kentucky NIDA AIDS Cooperative Agreement. Bivariate analyses indicated that
      in addition to the pattern of crack use, 13 of the candidate variables were
      significantly related to sex trading, ever and 11 related to sex trading in the
      past 90 days. The multivariate models accounted for more than 40% of the variance
      in sex trading, ever and almost 59% of the variance in sex trading over the past
      90 days. Suggestions for HIV/AIDS prevention and intervention among drug-involved
      women are discussed; implications for future research are suggested.

PMID- 16909325
TI  - Prevalence and correlates of condom use and HIV testing among female sex workers
      in Tashkent, Uzbekistan: implications for HIV transmission.
AB  - Little is known about sex work in Tashkent, Uzbekistan, despite rapid increases
      in HIV infection. Consistent client condom use and prior HIV testing are
      described among 448 female sex workers (FSW) completing a self-administered
      questionnaire, health provider interview, and HIV testing between April 2003 and
      March 2004. Participants were recruited through outreach workers using modified
      snowball sampling. Consistent client condom use was more likely for FSW who were
      married, knew condoms prevent HIV, and from countries in south Central Asia.
      Prior HIV testing was less likely for FSW younger than 21 years, who shared drugs
      with clients, initiated sex work at 18 years or less and had engaged in sex work
      less than 2 years. Low rates of condom use, particularly by those with risky drug
      behaviors, indicate that targeted risk-reduction interventions are urgently
      needed.

PMID- 16909326
TI  - CPPD complicating other forms of inflammatory arthritis.
AB  - Calcium pyrophosphate deposition (CPPD) disease is confirmed as equally common in
      rheumatoid arthritis by synovial fluid and macroscopic skeletal examination.
      Furthermore, differential frequencies in rheumatoid arthritis and
      spondyloarthropathy provide additional insights to the "lumper-splitter"
      question.

PMID- 16909327
TI  - Novel cardiovascular risk factors and cardiac event predictors in female inactive
      systemic lupus erythematosus patients.
AB  - Systemic lupus erythematosus (SLE) is associated with severe and premature
      cardiovascular disease, which cannot be explained by traditional risk factors
      alone. This study aims to investigate novel cardiovascular risk factors and
      cardiac event predictors in inactive SLE female patients who do not have any
      major cardiovascular risk factors. Twenty-five inactive (SLE disease activity
      index score <4) SLE female patients and 22 healthy control women were studied.
      SLE patients with a history of diabetes mellitus, hypertension, hyperlipidemia,
      smoking, or coronary artery disease (CAD) were excluded. Venous blood samples
      were analyzed for lipid subfractions and novel cardiovascular risk factors such
      as lipoprotein (a), homocysteine, fibrinogen, high-sensitivity C-reactive protein
      (hs-CRP), and serum amyloid A (SAA) levels. Endothelial dysfunction was assessed
      by flow-mediated dilatation (FMD) from the brachial artery at baseline and during
      reactive hyperemia. SLE patients and controls were similar in terms of age (40+/
      10 years vs 38+/-10 years, p = NS). No significant difference was found between
      the groups regarding family history of premature CAD, blood pressure, body mass
      index, lipoprotein (a), homocysteine, fibrinogen, SAA, apoprotein A-1 and B
      levels. Compared with the controls, SLE patients had higher levels of hs-CRP
      [median (range): 1.82 (0.02-0.98) vs 0.68 (0.02-0.35), p=0.04]. FMD was lower in
      SLE patients than controls (7.1+/-2.1 vs 11.4+/-1.2%, p<0.001). Increased levels
      of hs-CRP and decreased FMD were found in inactive SLE patients. Increased hs-CRP
      levels may reflect ongoing low-grade inflammation that could be a cause of
      impaired FMD in SLE patients. These findings suggest that SLE patients without
      traditional major cardiovascular risk factors may have increased risk of
      cardiovascular disease and future cardiac events.

PMID- 16909328
TI  - Characterization of humic materials extracted from hazelnut husk and hazelnut
      husk amended soils.
AB  - This study was carried out to determine effects of composted hazelnut husk (CHH)
      on some chemical properties of soil and soil humic acid (HA). Compost application
      increases organic matter (OM) content of the soil considerably, OM value of 3.18%
      became 3.89% in 3 years time interval. Before application of compost, the soil pH
      was found to be 5.37, while after compost application it became 5.61. FTIR
      characteristics of humic acid/humic acid-like materials extracted from the
      original hazelnut husk, composted hazelnut husk and composted hazelnut husk
      amended soil have been investigated. C and O content of humic acid-like/humic
      acid materials were in the range of 41.4-50.8% and 37.8-50.5%, respectively. The
      N content of the humic acid/humic acid-like materials are in the expected range
      for humic materials which is 2-6%. Comparison of FTIR spectra of hazelnut husk
      and composted hazelnut husk humic acid-like fractions shows that both exhibit
      similar but not identical series of IR bands indicating the presence of the same
      functional groups in both samples. The only difference in the spectra seemed to
      be a decrement in the peak intensities of composted sample compared to
      uncomposted one. The similar differentiation of the intensities of IR bands of
      compost applied soil sample has also been observed. The FTIR spectral results
      show that the characteristics of composted material tend to become similar to
      that of soil humic acids characteristics in time.

PMID- 16909329
TI  - Mineral surface directed membrane assembly.
AB  - The transition from non-living to living matter may have resulted from the self
      organizing properties of organic molecules and their interactions with a
      chemically rich inorganic environment. We have shown that a solution containing
      RNA, fatty acids and clay produces structures that contain a potentially
      catalytic surface (clay) and a potential informational biopolymer (RNA)
      encapsulated within a membrane. This highlights the ability of mineral surfaces
      to bring together and organize key components of primordial life. We have
      extended our analysis of mineral-mediated vesicle catalysis to include other
      natural minerals and synthetic surfaces of varying shape, size, and charge
      density. Our results show that while RNA polymerization on minerals may be
      restricted to the surface environment provided by montmorillonite, vesicle
      formation is enhanced in the presence of disparate types of surfaces. A model is
      presented in which new sheets of amphiphiles form just proximal to a surface.
      Similar interactions between amphiphiles and minerals on early Earth may have
      resulted in the encapsulation of a diverse array of mineral particulates with
      catalytic properties.

PMID- 16909330
TI  - Intramolecular RNA replicase: possibly the first self-replicating molecule in the
      RNA world.
AB  - Although there is more and more evidence suggested the existence of an RNA World
      during the origin of life, the scenario concerning the origin of the RNA World
      remains blurry. Usually it is speculated that it originated from a prebiotic
      nucleotide pool, during which a self-replicating RNA synthesis ribozyme may have
      emerged as the first ribozyme - the RNA replicase. However, there is yet no
      ersuasive supposition for the mechanism for the self-favouring feature of the
      replicase, thus the speculation remains unconvincing. Here we suggest that
      intramolecular catalysis is a possible solution. Two RNA synthesis ribozymes may
      be integrated into one RNA molecule, as two functional domains which could
      catalyze the copy of each other. Thus the RNA molecule could self-replicate and
      be referred to as "intramolecular replicase" here. Computational simulation to
      get insight into the dynamic mechanism of emergence of the intramolecular
      replicase from a nucleotide pool is valuable and would be included in a following
      work of our group.

PMID- 16909331
TI  - Palladium and gold removal and recovery from precious metal solutions and
      electronic scrap leachates by Desulfovibrio desulfuricans.
AB  - Biomass of Desulfovibrio desulfuricans was used to recover Au(III) as Au(0) from
      test solutions and from waste electronic scrap leachate. Au(0) was precipitated
      extracellularly by a different mechanism from the biodeposition of Pd(0). The
      presence of Cu(2+) ( approximately 2000 mg/l) in the leachate inhibited the
      hydrogenase-mediated removal of Pd(II) but pre-palladisation of the cells in the
      absence of added Cu(2+) facilitated removal of Pd(II) from the leachate and more
      than 95% of the Pd(II) was removed autocatalytically from a test solution
      supplemented with Cu(II) and Pd(II). Metal recovery was demonstrated in a gas
      lift electrobioreactor with electrochemically generated hydrogen, followed by
      precipitation of recovered metal under gravity. A 3-stage bioseparation process
      for the recovery of Au(III), Pd(II) and Cu(II) is proposed.

PMID- 16909332
TI  - Chromosome rearrangements in Pectinidae (Bivalvia: Pteriomorphia) implied based
      on chromosomal localization of histone H3 gene in four scallops.
AB  - Chromosomal structural rearrangement in four scallops, Chlamys farreri (n=19),
      Patinopecten yessoensis (n=19), Chlamys nobilis (n=16) and Argopecten irradians
      (n=16), was studied by fluorescence in situ hybridization using histone H3 gene
      probes. The results show that histone H3 gene sites differ strikingly with regard
      to number, location, and intensity among, or even within these species. For
      example, two histone H3 gene loci were detected on the metaphase chromosomes of
      P. yessoensis, while one locus was found in the others. In P. yessoensis,
      differing intensities of hybridization signals were detected between homologues 5
      and 11, and within homologue 11. These data suggest that the histone H3 gene is a
      qualified chromosome marker for the preliminary understanding of the historical
      chromosomal reconstructing of the Pectinidae family. The variable distribution
      patterns of the histone H3 gene suggest that gene duplication/diminution as well
      as chromosome rearrangements by inversion and translocation may have played
      important roles in the genomic evolution of Pectinidae. We also compiled our
      present results with former published data regarding the chromosome mapping of
      rDNAs in species of the Pectinidae family. Such comparative chromosomal mapping
      should improve our understanding of historical chromosomal reconstructions of
      modern-day scallops.

PMID- 16909333
TI  - Identification and detection of genetic relatedness among important varieties of
      pea (Pisum sativum L.) grown in India.
AB  - Among the cool season legume crops grown in India and the Indian sub-continent,
      peas are very popular and preferred by the growers as well as consumers for
      various uses. The third largest area in pea cultivation is occupied by India
      after Canada and Russia. Among the important and popular varieties of peas that
      are grown in India, several are from exotic background. But very little work has
      been done to carry out the genetic diversity present in the widely adapted Indian
      pea varieties using DNA markers. Twenty-four most popular and widely adapted
      varieties were subjected to RAPD analysis to find out the genetic relatedness
      among them using 60 decamer primers. All the primers used in our study were found
      to be polymorphic and seven of them showed 100% polymorphism. Out of 579
      amplified products, 433 showed polymorphism (74.8%). On an average, 9.65 bands
      were amplified per primer. Cluster analysis based on Jaccard's similarity
      coefficient using UPGMA grouped all the tall type varieties together, whereas,
      dwarf types formed two different clusters based upon their pedigree. The
      arithmetic mean heterozygosity (Hav) value and marker index (MI) was found to be
      0.496 and 4.787, respectively, thus this indicated the efficiency of RAPD as a
      marker system. Moreover, the calculated value of probability of identical match
      by chance suggested that about 10(53) genotypes can be unambiguously distinguish
      by employing 60 RAPD primers.

PMID- 16909334
TI  - Cytogenetic mapping of immunoglobulin heavy chain genes in Antarctic fish.
AB  - The chromosomal location of the IgH locus has been analyzed in several bony fish
      of the Antarctic perciform group Notothenioidei. Two IgH probes were prepared
      from the species Trematomus bernacchii (family Nototheniidae, tribe Trematominae)
      and mapped onto the chromosomes of ten species belonging to the same genus
      (Trematomus) and in two outgroups, through one-color and two-color FISH. A single
      location of the IgH locus was found in the majority of the species examined,
      including the outgroups, whereas in four of them the IgH genes splited to two
      chromosomal loci. RT-PCR experiments revealed the presence of three allelic
      sequences in T. newnesi, a species in which the IgH genes were organized in two
      chromosomal loci. Possible pathways leading to IgH genes duplication during the
      diversification of trematomine fishes were inferred from the analysis of the FISH
      patterns in a phylogenetic context. The present work provides the first
      comprehensive picture of IgH genes organization at chromosomal level in a bony
      fish group.

PMID- 16909335
TI  - "More on respect for embryos and potentiality: does respect for embryos entail
      respect for in vitro embryos?".
AB  - It is commonly assumed that persons who hold abortions to be generally
      impermissible must, for the same reasons, be opposed to embryonic stem cell
      research [ESR]. Yet a settled position against abortion does not necessarily
      direct one to reject that research. The difference in potentiality between the
      embryos used in ESR and embryos discussed in the abortion debate can make ESR
      acceptable even if one holds that abortion is impermissible. With regard to their
      potentiality, in vitro embryos are here argued to be more morally similar to
      clonable somatic cells than they are to in vivo embryos. This creates an
      important moral distinction between embryos in vivo and in vitro. Attempts to
      refute this moral distinction, raised in the recent debate in this journal
      between Alfonso Gomez-Lobo and Mary Mahowald, are also addressed.

PMID- 16909336
TI  - Electrophysiology of turgor regulation in marine siphonous green algae.
AB  - We review electrophysiological measures of turgor regulation in some siphonous
      green algae, primarily the giant-celled marine algae, Valonia and Ventricaria,
      with particular comparison to the well studied charophyte algae Chara and
      Lamprothamnium. The siphonous green algae have a less negative plasma membrane
      potential, and are unlikely to have a proton-based chemiosmotic transport system,
      dominated by active electrogenic K(+) uptake. We also make note of the unusual
      cellular structure of the siphonous green algae. Hypertonic stress, due to
      increased external osmotic pressure, is accompanied by positive-going potential
      difference (PD), increase in conductance, and slow turgor regulation. The
      relationship between these is not yet resolved, but may involve changes in K(+
      )conductance (G (K)) or active K(+) transport at both membranes. Hypotonic turgor
      regulation, in response to decreased external osmotic pressure, is approximately
      3 times faster than hypertonic turgor regulation. It is accompanied by a negative
      going PD, although conductance also increases. The conductance increase and the
      magnitude of the PD change are strongly correlated with the magnitude of
      hypotonic stress.

PMID- 16909337
TI  - Strengths and limits of Beta distributions as a means of reconstructing the true
      single-channel current in patch clamp time series with fast gating.
AB  - Single-channel current seems to be one of the most obvious characteristics of ion
      transport. But in some cases, its determination is more complex than anticipated
      at first glance. Problems arise from fast gating in time series of patch-clamp
      current, which can lead to a reduced apparent (measured) single-channel current.
      Reduction is caused by undetected averaging over closed and open intervals in the
      anti-aliasing filter. Here it is shown that fitting the measured amplitude
      histograms by Beta distributions is an efficient tool of reconstructing the true
      current level from measured data. This approach becomes even more powerful when
      it is applied to amplitude distributions-per-level. Simulated time series are
      employed to show that the error sum is a good guideline for finding the correct
      current level. Furthermore, they show that a Markov model smaller than the one
      used for gating analysis can be used for current determination (mostly O-C, i.e.,
      open-closed). This increases the reliability of the Beta fit. The knowledge of
      the true current level is not only important for the understanding of the
      biophysical properties of the channel. It is also a prerequisite for the correct
      determination of the rate constants of gating. The approach is applied to
      measured data. The examples reveal the limits of the analysis imposed by the
      signal-to-noise ratio and the shape of the amplitude distribution. One
      application shows that the negative slope of the I-V curve of the human MaxiK
      channel expressed in HEK293 cells is caused by fast gating.

PMID- 16909339
TI  - Characterization of recombinant human cardiac KCNQ1/KCNE1 channels (I (Ks))
      stably expressed in HEK 293 cells.
AB  - The present study was designed to characterize pharmacological, biophysical and
      electrophysiological properties of the recombinant human cardiac I (Ks)
      (KCNQ1/KCNE1) channels at physiological temperature. Human cardiac KCNQ1 and
      KCNE1 genes were cotransfected into HEK 293 cells, and a cell clone stably
      expressing both genes was selected. Membrane currents were recorded using a
      perforated patch-clamp technique. The typical I (Ks) was slowly activated upon
      depolarization voltages in HEK 293 cells stably expressing human cardiac KCNQ1
      and KCNE1 genes, and the current was inhibited by I (Ks) blockers HMR 1556 and
      chromanol 293B, with 50% inhibitory concentrations (IC(50)s) of 83.8 nM: and 9.2
      muM: , respectively. I (Ks) showed a significant temperature-dependent increase
      in its magnitude upon elevating bath temperature to 36 degrees C from room
      temperature (21 degrees C). The current was upregulated by the beta-adrenoceptor
      agonist isoproterenol, and the effect was reversed by H89. In addition, I (Ks)
      was inhibited by Ba(2+) in a concentration-dependent manner (IC(50) = 1.4 mM).
      Action potential clamp revealed a "bell-shaped" time course of I (Ks) during the
      action potential, and maximal peak current was seen at the plateau of the action
      potential. A significant use- and frequency-dependent increase of I (Ks) was
      observed during a train of action potential clamp. These results indicate that
      the recombinant human cardiac I (Ks) stably expressed in HEK 293 cells is similar
      to native I (Ks) in drug sensitivity and regulated by Ba(2+) and beta
      adrenoceptor via the cyclic adenosine monophosphate/protein kinase A pathway.
      Importantly, the current exhibits significant temperature dependence, a bell
      shaped time course during action potential and prominent use- or frequency
      dependent accumulation during a train of action potentials.

PMID- 16909338
TI  - Intracellular monovalent ions as second messengers.
AB  - It is generally accepted that electrochemical gradients of monovalent ions across
      the plasma membrane, created by the coupled function of pumps, carriers and
      channels, are involved in the maintenance of resting and action membrane
      potential, cell volume adjustment, intracellular Ca(2+ )handling and accumulation
      of glucose, amino acids, nucleotides and other precursors of macromolecular
      synthesis. In the present review, we summarize data showing that side-by-side
      with these classic functions, modulation of the intracellular concentration of
      monovalent ions in a physiologically reasonable range is sufficient to trigger
      numerous cellular responses, including changes in enzyme activity, gene
      expression, protein synthesis, cell proliferation and death. Importantly, the
      engagement of monovalent ions in regulation of the above-listed cellular
      responses occurs at steps upstream of Ca(2+) (i) and other key intermediates of
      intracellular signaling, which allows them to be considered as second messengers.
      With the exception of HCO (3) (-) -sensitive soluble adenylyl cyclase, the
      molecular origin of sensors involved in the function of monovalent ions as second
      messengers remains unknown.

PMID- 16909340
TI  - Mimetic membrane system to carry multiple antigenic proteins from Leishmania
      amazonensis.
AB  - Liposomes have long been used as models for lipid membranes and for the
      reconstitution of a single or multiple proteins. Also, liposomes have adjuvant
      activity in vaccines against several protozoan or bacterial organisms. Thus, the
      main objective of the present study was to obtain a crude extract of detergent
      solubilized proteins of Leishmania amazonensis amastigotes and reconstitute them
      into liposomes. Neutral and zwiterionic detergents were less efficient than an
      ionic detergent. In order to obtain efficient solubilization using only sodium
      dodecyl sulfate (SDS), the effects of detergent and protein concentration and
      incubation time were studied. The maximum of solubilized proteins was obtained
      instantaneously using a ratio of 0.5 mg/ml of protein to 0.1% (w/v) detergent at
      4 degrees C. Dipalmitoylphosphatidylcholine (DPPC), dipalmitoylphosphatidylserine
      (DPPS) and cholesterol in a weight ratio of 5:1:4 were used for protein
      reconstitution into liposomes using the cosolubilization method, yielding 60% of
      incorporation. The incorporation of multiple parasite proteins results in a
      vesicular diameter of proteoliposomes of about 140 nm, presenting a final lipid
      weight ratio for DPPC, DPPS and cholesterol of 1:1:5, with high stability. The
      detergent-solubilized proteins of L. amazonensis amastigotes present in the
      proteoliposome, when analyzed by SDS-polyacrylamide gel electrophoresis, include
      a wide range of parasite-incorporated proteins. BALB/c mice inoculated with these
      proteoliposomes were able to produce antibodies against the proteins
      reconstituted in DPPC:DPPS:cholesterol liposomes and were partially resistant to
      infection with L. amazonensis promastigotes. These results indicate that this
      system can be used as a possible vaccine against L. amazonensis.

PMID- 16909341
TI  - Vitamins C and E modulate neuronal potassium currents.
AB  - We investigated the effects of vitamins C and E on the delayed-rectifier
      potassium current (IK(DR)), which is important in repolarizing the membrane
      potential, and on the transient A-type potassium current (IK(A)), which regulates
      neuronal firing frequency. The whole-cell patch-clamp technique was used to
      measure the currents from cultured Drosophila neurons derived from embryonic
      neuroblasts. The membrane potential was stepped to different voltages between -40
      and +60 mV from a holding potential of -80 mV. IK(DR) and IK(A) measured in the
      vitamin C-containing solution (IK(DR) 305 +/- 16 pA, IK(A) 11 +/- 2 pA) were
      smaller than those measured in the control solution (488 +/- 21 pA, IK(A )28 +/-
      3 pA). By contrast, IK(DR) and IK(A) measured in the vitamin E-containing
      solution (IK(DR) 561 +/- 21 pA, IK(A )31 +/- 3 pA) were greater than those
      measured in the control solution (422 +/- 15 pA, 17 +/- 2 pA). These results
      indicate that vitamins C and E can modulate potassium current amplitudes and
      possibly lead to altered neuronal excitability.

PMID- 16909342
TI  - Fungi in the hyporheic zone of a springbrook.
AB  - Eight bimonthly sediment core samples (n = 6) were collected, to a depth of 64
      cm, from the hyporheic zone of a springbrook in southern Ontario, Canada.
      Sediment cores were divided into three to four sections, and organic matter was
      subdivided into six different categories. Twigs were the most common substrate,
      followed by roots, cedar leaves, wood, grass, and deciduous leaves. The
      contributions of deciduous and cedar leaves declined with depth, whereas that of
      wood increased. On each sampling date and from each section, three randomly
      chosen substrates >3 cm were examined for conidia of aquatic hyphomycetes. The
      number of identified species significantly decreased with depth, and was highest
      on deciduous leaves and lowest on wood. Season had no significant effect on
      species numbers. DNA from substrates was extracted, amplified with fungal
      primers, and differentiated into phylotypes with denaturing gradient gel
      electrophoresis (DGGE). Absence/presence patterns of phylotype were significantly
      affected by season but not by section level. Both season and section level
      significantly affected relative densities of the bands of the 10 most common
      phylotypes. Our data suggest that aquatic hyphomycetes and other fungi readily
      disperse within the hyporheic zone, and that their relative scarcity in this
      habitat is due to a lack of suitable substrates.

PMID- 16909343
TI  - Biogeography and landscape-scale diversity of the dominant Crenarchaeota of soil.
AB  - We surveyed the diversity of soil Archaea across a large scale elevational
      gradient of ecosystem types, from foothills forest to alpine tundra in the Front
      Range of the Rocky Mountains. We used a dilution technique to sequence the single
      most abundant archaeal 16S rDNA sequence in each of the 40 soil cores distributed
      across the gradient to compare our results to those of typical 16S clone library
      studies. We found a greater diversity of sequences than has typically been found
      in clone library studies from a single site or core, identifying sequences both
      from the Terrestrial Group and the FFSB Group at several sites. We did not
      observe any significant environmental correlates with the dominant sequence type,
      nor was there any relationship between the spatial distance between samples and
      the phylogenetic similarity of the dominant sequence types. Despite using a very
      different methodology, our collective results are in remarkably good agreement
      with other studies of soil Crenarchaeota in terms of the diversity and relative
      abundance of sequence types identified. We are able to identify two instances of
      very tightly clustered sequences which we suggest are the results of global
      selective sweeps-one closely related to SCA1145, an abundant globally distributed
      group within the Terrestrial Group of Crenarchaeota, and another nested within
      the more basal FFSB group of sequences. We replicated our sequence results at two
      levels: first, by repeating the dilution and PCR processes from the same soil
      core DNA extraction, and second, by performing a replicate DNA extraction from
      the same homogenized soil core sample. Pairs of sequences produced by the
      dilution replicates were significantly more similar than the pairs of sequences
      produced by the extraction replicates, suggesting that soil Crenarchaeota exists
      in highly localized and discrete clonal populations.

PMID- 16909344
TI  - Seasonal dynamics of microbial community composition and function in oak canopy
      and open grassland soils.
AB  - Soil microbial communities are closely associated with aboveground plant
      communities, with multiple potential drivers of this relationship. Plants can
      affect available soil carbon, temperature, and water content, which each have the
      potential to affect microbial community composition and function. These same
      variables change seasonally, and thus plant control on microbial community
      composition may be modulated or overshadowed by annual climatic patterns. We
      examined microbial community composition, C cycling processes, and environmental
      data in California annual grassland soils from beneath oak canopies and in open
      grassland areas to distinguish factors controlling microbial community
      composition and function seasonally and in association with the two plant
      overstory communities. Every 3 months for up to 2 years, we monitored microbial
      community composition using phospholipid fatty acid (PLFA) analysis, microbial
      biomass, respiration rates, microbial enzyme activities, and the activity of
      microbial groups using isotope labeling of PLFA biomarkers (13C-PLFA). Distinct
      microbial communities were associated with oak canopy soils and open grassland
      soils and microbial communities displayed seasonal patterns from year to year.
      The effects of plant species and seasonal climate on microbial community
      composition were similar in magnitude. In this Mediterranean ecosystem, plant
      control of microbial community composition was primarily due to effects on soil
      water content, whereas the changes in microbial community composition seasonally
      appeared to be due, in large part, to soil temperature. Available soil carbon was
      not a significant control on microbial community composition. Microbial community
      composition (PLFA) and 13C-PLFA ordination values were strongly related to intra
      annual variability in soil enzyme activities and soil respiration, but microbial
      biomass was not. In this Mediterranean climate, soil microclimate appeared to be
      the master variable controlling microbial community composition and function.

PMID- 16909345
TI  - Microbial community structure in three deep-sea carbonate crusts.
AB  - Carbonate crusts in marine environments can act as sinks for carbon dioxide.
      Therefore, understanding carbonate crust formation could be important for
      understanding global warming. In the present study, the microbial communities of
      three carbonate crust samples from deep-sea mud volcanoes in the eastern
      Mediterranean were characterized by sequencing 16S ribosomal RNA (rRNA) genes
      amplified from DNA directly retrieved from the samples. In combination with the
      mineralogical composition of the crusts and lipid analyses, sequence data were
      used to assess the possible role of prokaryotes in crust formation. Collectively,
      the obtained data showed the presence of highly diverse communities, which were
      distinct in each of the carbonate crusts studied. Bacterial 16S rRNA gene
      sequences were found in all crusts and the majority was classified as alpha-,
      gamma-, and delta- Proteobacteria. Interestingly, sequences of Proteobacteria
      related to Halomonas and Halovibrio sp., which can play an active role in
      carbonate mineral formation, were present in all crusts. Archaeal 16S rRNA gene
      sequences were retrieved from two of the crusts studied. Several of those were
      closely related to archaeal sequences of organisms that have previously been
      linked to the anaerobic oxidation of methane (AOM). However, the majority of
      archaeal sequences were not related to sequences of organisms known to be
      involved in AOM. In combination with the strongly negative delta 13C values of
      archaeal lipids, these results open the possibility that organisms with a role in
      AOM may be more diverse within the Archaea than previously suggested. Different
      communities found in the crusts could carry out similar processes that might play
      a role in carbonate crust formation.

PMID- 16909346
TI  - Variation in microbial community composition and culturability in the rhizosphere
      of Leucanthemopsis alpina (L.) Heywood and adjacent bare soil along an alpine
      chronosequence.
AB  - We compared the size, culturability, diversity, and dominant species similarity
      of the bacterial communities of Leucanthemopsis alpina (L.) Heywood rhizosphere
      and adjacent bare soil (interspace) along a chronosequence of soil development
      time (5, 50, and 70 years) in the forefield of the Dammaglacier (Switzerland). We
      found no evidence that the size of the bacterial community was significantly
      affected by either soil age or the presence of L. alpina. In contrast, the
      proportion of the bacterial community that could be cultured on nonselective
      agars, and which was taken as an indication of the proportion of r-selected
      populations, was significantly higher in the 50- and 70-year-old soils than in
      the 5-year-old soil, and was also significantly higher in the rhizosphere of L.
      alpina at all time points. RDA indicated significant correlations between the
      increased culturability of the bacterial community over time and increasing
      concentrations of labile N, and between the increased culturability in the
      rhizosphere and increased concentrations of labile C and N. HaeIII-amplified
      ribosomal DNA (rDNA) restriction analysis of a library of 120 clones of 16S rDNA
      revealed 85 distinct phylotypes. Hurlbert's probability of interspecific
      encounter (PIE) values derived from this library ranged from 0.95 to 1.0,
      indicating a very high genetic diversity. There was no significant difference in
      the PIE values of rhizosphere and interspace communities. Detrended
      correspondence analysis (DCA) of 16S ribosomal RNA (rRNA) denaturing gradient gel
      electrophoresis (DGGE) community profiles clearly distinguished the rhizosphere
      from the interspace community in the 5-year-old soils and also clearly
      distinguished between these communities and the rhizosphere and interspace
      communities of the 50- and 70-year-old soils. However, 16S rRNA DGGE revealed
      little difference between rhizosphere and interspace communities in the 50- and
      70-year-old soils. The relative similarity of the 16S rRNA profiles strongly
      reflected labile carbon and nitrogen availability. Overall, our results suggest
      that improved C and N availability in the rhizosphere of L. alpina increases the
      size of r-selected bacterial species populations, but that the influence of L.
      alpina depends on soil age, being maximal in the youngest soils and minimal in
      the oldest. The reduced influence of L. alpina in the older soils may reflect a
      feedback between improved nutrient availability and reduced rhizodeposition.

PMID- 16909347
TI  - Large-scale variation in subsurface stream biofilms: a cross-regional comparison
      of metabolic function and community similarity.
AB  - We examined bacterial metabolic activity and community similarity in shallow
      subsurface stream sediments distributed across three regions of the eastern
      United States to assess whether there were parallel changes in functional and
      structural attributes at this large scale. Bacterial growth, oxygen consumption,
      and a suite of extracellular enzyme activities were assayed to describe
      functional variability. Community similarity was assessed using randomly
      amplified polymorphic DNA (RAPD) patterns. There were significant differences in
      streamwater chemistry, metabolic activity, and bacterial growth among regions
      with, for instance, twofold higher bacterial production in streams near
      Baltimore, MD, compared to Hubbard Brook, NH. Five of eight extracellular enzymes
      showed significant differences among regions. Cluster analyses of individual
      streams by metabolic variables showed clear groups with significant differences
      in representation of sites from different regions among groups. Clustering of
      sites based on randomly amplified polymorphic DNA banding resulted in groups with
      generally less internal similarity although there were still differences in
      distribution of regional sites. There was a marginally significant (p = 0.09)
      association between patterns based on functional and structural variables. There
      were statistically significant but weak (r2 approximately 30%) associations
      between landcover and measures of both structure and function. These patterns
      imply a large-scale organization of biofilm communities and this structure may be
      imposed by factor(s) such as landcover and covariates such as nutrient
      concentrations, which are known to also cause differences in macrobiota of stream
      ecosystems.

PMID- 16909348
TI  - Concurrence of cat and tet genes in multiple antibiotic-resistant bacteria
      isolated from a sea cucumber and sea urchin mariculture farm in China.
AB  - A basic understanding of abundance and diversity of antibiotic-resistant microbes
      and their genetic determinants is necessary for finding a way to prevent and
      control the spread of antibiotic resistance. For this purpose, chloramphenicol
      and multiple antibiotic-resistant bacteria were screened from a mariculture farm
      in northern China. Both sea cucumber and sea urchin rearing ponds were populated
      with abundant antibiotic-resistant bacteria, especially marine vibrios. Sixty
      five percent chloramphenicol-resistant isolates from sea cucumber harbored a cat
      gene, either cat IV or cat II, whereas 35% sea urchin isolates harbored a cat
      gene, actually cat II. The predominant resistance determinant cat IV gene mainly
      occurred in isolates related to Vibrio tasmaniensis or Pseudoalteromonas
      atlantica, and the cat II gene mainly occurred in Vibrio splendidus-like
      isolates. All the cat-positive isolates also harbored one or two of the tet
      genes, tet(D), tet(B), or tet(A). As no chloramphenicol-related antibiotic was
      ever used, coselection of the cat genes by other antibiotics, especially
      oxytetracycline, might be the cause of the high incidence of cat genes in the
      mariculture farm studied.

PMID- 16909350
TI  - Host selectivity and genetic variation of Discula umbrinella isolates from two
      oak species: analyses of intergenic spacer region sequences of ribosomal DNA.
AB  - Discula umbrinella, a fungal endophyte of oak species, colonizes and reproduces
      on leaves of Quercus alba and Q. rubra in forest ecosystems. Twenty-nine isolates
      collected from leaves of both oak species (16 from Q. alba and 13 from Q. rubra)
      were assayed for oak species preference and genetic variation based on primer
      specific polymerase chain reactions for the intergenic spacer region (IGS) of
      ribosomal DNA. DNA sequencing of the polymerase chain reaction products revealed
      a 10-bp insertion (237-247 bp) at the 3' end of the IGS region present in nine
      isolates and absent in 20 of the isolates. Phylogenetic analysis of the IGS
      region using the neighbor-joining method identified IGS groups (groups I-V) based
      on single nucleotide sequence differences. Host selectivity and geographic origin
      of isolates were correlated in some instances with the IGS groups. Isolates
      within each IGS group were further analyzed for nucleotide polymorphisms to
      confirm genotype identity and genotype diversity. Ten different genotypes (Va-Vj)
      were identified among the isolates analyzed. Genotype diversity was greatest in
      IGS groups I, IV, and V. Seventy percent of the genotypes (Vc, Vd, Ve, Vf, Vg,Vi,
      and Vj) contained isolates with single tree species preferences.

PMID- 16909351
TI  - Recurrent laryngeal nerve monitoring during thyroid surgery in childhood.
AB  - INTRODUCTION: Diseases of the thyroid gland are one of the most common
      endocrinopathies in childhood. Neither benign nor malignant thyroid diseases are
      often treated surgically. But if surgical treatment is carried out,
      intraoperative damage of the recurrent laryngeal nerve (RLN) is a common and
      severe complication. In adult surgery, therefore, intraoperative monitoring (IOM)
      of the RLN is a method which has been used since several years. The question is
      whether this method can be used in paediatric surgery for the identification and
      functional control of the integrity of the RLN. METHODS: Surgical treatment of
      benign (9 x) or malignant (1 x) thyroid diseases was performed in ten children
      (median age: 13 years) with 16 nerves at risk (NAR). The function of the vocal
      cord was controlled in all children before and after surgery. Intraoperative
      identification and functional control of the recurrent nerve was performed using
      the Neurosign 100, placing a needle electrode transligamentously into the vocal
      muscle. All results before and after resection were documented. RESULTS: A clear
      and reliable identification of the RLN was possible in all cases. All NAR showed
      a constant physiological nerve signal before and after surgical resection of the
      thyroid gland. However in one young patient the postoperative control of the
      vocal cord revealed a partial paralysis despite the constant intraoperative
      signal of the RLN. The control on this patient after a period of six months
      showed a normal function. CONCLUSION: IOM of the RLN as used in adult surgery
      could easily be used in paediatric surgery as well. A clear and positive
      identification of the RLN was possible in all these patients. Therefore, IOM of
      the RLN could develop into a helpful and easy method for the prevention of
      intraoperative damage of the recurrent laryngeal nerve during thyroid surgery in
      childhood.

PMID- 16909349
TI  - Consistent bacterial community structure associated with the surface of the
      sponge Mycale adhaerens bowerbank.
AB  - As a crucial step in the identification of possible association between bacteria
      and sponges, we investigated if a unique bacterial population community was
      consistently associated with the surface of the sponge Mycale adhaerens,
      irrespective of environmental conditions. The composition of bacterial
      communities associated with the surface of sponges at three geographically
      distinctive sites in Hong Kong waters over four seasons was examined by analyzing
      terminal restriction fragment length polymorphism of the bacterial 16S rRNA
      genes. Statistical analysis indicated that bacterial communities on inanimate
      reference surfaces (polystyrene dishes deployed in the close vicinity of the
      sponge colonies for 7 days) had a relatively high degree of both site and
      seasonal specificities (R statistics of pairwise comparisons approximately 1),
      which might be attributed to the differences in environmental conditions at
      different sites and seasons. On the contrary, the sponge-surface-associated
      bacterial communities from different sites and seasons were hardly
      distinguishable from each other (lowest R = -0.16) but were rather distinctive
      from the reference bacterial communities (R approximately 1), suggesting a highly
      stable and distinctive bacteria-sponge association irrespective of the
      environmental conditions. The occurrence of some unique bacterial types in the
      sponge-surface-associated communities over space and time suggests that the
      associations are consistent and specific.

PMID- 16909352
TI  - Preliminary study on the effects of bar placement on the thorax after the nuss
      procedure for pectus excavatum using bone scintigraphy.
AB  - AIM: Bone scintigraphy was performed to elucidate the effects of the Nuss
      procedure for pectus excavatum on the bony thorax. METHODS: Eight boys and 6
      girls (5 - 24 years of age) underwent bone scintigraphy, using (99m)Tc-HMDP.
      Eleven patients were studied 5 to 21 days after the Nuss procedure; 6 were
      studied 20 to 24 months after the operation before bar removal. Three of 14 were
      studied twice after the Nuss procedure and before bar removal. RESULTS: In the
      early postoperative phase, RI accumulation was found at the sternum and ribs in
      only 1 of 6 patients under 9 years of age, whereas in all 5 older patients, RI
      had accumulated at the sternum. Scintigrams before bar removal revealed,
      regardless of age, hot spots at the lateral ribs in contact with the bar and at
      the costochondral junctions where the bar passed through the intercostal spaces.
      Furthermore, chest roentgenograms showed the deformed lateral ribs in contact
      with the bar. CONCLUSIONS: The Nuss procedure creates minute fractures at the
      sternum and the ribs, especially in older patients. The bar deforms the ribs and
      restrains the growth of the thorax. Furthermore, it constantly rubs against the
      ribs and can therefore cause late complications. Bone scintigraphy may determine
      the appropriate timing for bar removal.

PMID- 16909353
TI  - Lung morphology after late fetal tracheal ligation in rats.
AB  - Pulmonary hypoplasia and persistent pulmonary hypertension are the main causes of
      mortality and morbidity in congenital diaphragmatic hernia (CDH). Prenatal
      tracheal occlusion accelerates lung growth, but the mechanism remains unknown. In
      order to be able to establish the accuracy of our experimental model for further
      molecular biological examinations, we evaluated the histologic structure of 1.
      fetal lungs subjected to tracheal occlusion compared to 2. normal fetal lungs, 3.
      hypoplastic lungs in CDH, and 4. normal neonatal lungs. One group of Sprague
      Dawley rat fetuses were subjected to intrauterine tracheal ligation (TL) on
      gestational day 19 (n = 7). Control fetuses were obtained from the same litters
      as those subjected to TL (n = 8). Another group of pregnant Sprague-Dawley rats
      were given 100 mg nitrofen on gestational day 9.5 to create CDH (n = 8). All
      fetuses were delivered by cesarean section on day 21. Lungs from 1-day-old,
      healthy, non-operated, newborn Sprague-Dawley rats were also examined (n = 6).
      Lung weight to body weight ratio was significantly higher in the TL lungs (5.0 +/
      0.36 %), compared to control lungs (2.8 +/- 0.15 %), CDH lungs (1.9 +/- 0.12 %),
      and normal neonatal lungs (4.2 +/- 0.18 %). Volume density of alveolar air space
      and radial alveolar count (RAC) in TL lungs (52 +/- 1.4 %) (3.3 +/- 0.25) were
      significantly higher than in control lungs (34 +/- 3.4 %) (2.2 +/- 0.17) and in
      CDH lungs (16 +/- 1.7 %) (1.7 +/- 0.07). No significant differences were found
      between the TL and the normal neonatal group (59 +/- 1.4 %) (3.6 +/- 0.11). Fetal
      lungs after TL showed evidence of growth stimulation with increased volume
      density of alveolar air space and increased RAC, comparable to findings in normal
      neonatal lungs.

PMID- 16909355
TI  - Experience of 49 longitudinal intestinal lengthening procedures for short bowel
      syndrome.
AB  - PATIENTS, METHODS AND RESULTS: Forty-nine patients with a mean age of 25 months
      underwent a longitudinal intestinal lengthening procedure for short bowel
      syndrome (SBS) in our institution. Indications for the operation were dependence
      on parenteral nutrition in spite of adequate conservative management. The small
      bowel was lengthened from a mean of 27 cm to a mean of 51 cm. There was no
      intraoperative mortality. The following early complications occurred in our early
      series: ischemia of a short bowel segment of 2 cm, requiring resection in two
      patients, insufficiency of the longitudinal anastomosis in two patients and an
      intra-abdominal abscess in one. Four of 9 non-survivors died of liver failure and
      3 of sepsis. Follow-up showed that 19 patients were weaned from parenteral
      nutrition after a mean of 9.1 months. Long-term complications encountered were
      dismotility with malabsorption due to bacterial overgrowth caused by progressive
      dilatation of the bowel, d-lactic acidosis, cholelithiasis and urolithiasis.
      CONCLUSIONS: A longitudinal intestinal lengthening procedure is an effective and
      safe surgical approach for SBS, provided it is performed in time, the patient's
      preoperative condition is optimized and technical surgical details are taken into
      account.

PMID- 16909354
TI  - Complications occurring during conservative management of splenic trauma in
      children.
AB  - AIM: Conservative management of splenic rupture in haemodynamically stable
      children is now generally accepted. However, during follow-up, many complications
      can occur. The aim of this study was to describe the complications we observed
      and to propose a standardised follow-up adapted to them. METHODS: Between March
      1992 and December 2002 we managed 65 children (aged between 3 and 15 years old)
      with accidental splenic rupture. Follow-up and treatment consisted of a 10-day
      bed rest with sonogram and Doppler controls on the 5th and 10th day and
      subsequently every month until complete healing. Complications included secondary
      haemorrhage in 3 cases, cystic evolution in 5 cases, and pseudo-aneurysm in 2
      cases. All were treated by renewed bed rest. Three of the cysts resolved
      spontaneously, the other two underwent cystic resection and epiploplasty by
      laparotomy (n = 1) or laparoscopy (n = 1) and both pseudo-aneurysms were
      selectively embolised. There were no splenectomies. CONCLUSIONS: Complications
      essentially occurred in older children and were not related to gender, type of
      fracture, or extent of bleeding. Cystic evolution of the sub-capsular haematomas
      can appear up to 1 month after trauma. Peripheral pseudo-aneurysms which could be
      responsible for secondary haemorrhages were selectively embolised. We favour the
      use of the Doppler sonogram for follow-up until total recovery of these patients,
      even in low-grade traumas. Considering the number of complications encountered we
      do not believe the American evidence-based guidelines are suitable for our
      population.

PMID- 16909356
TI  - Calyceal plication with pyeloplasty in the treatment of giant hydronephrosis in
      children.
AB  - The relief of obstruction alone is frequently not sufficient to ensure renal
      salvage in giant hydronephrosis. We report on our experience with plication of
      the renal calyces used as an adjunct to dismembered pyeloplasty in patients with
      giant hydronephrosis. We describe the operative technique and outcomes in ten
      children after a follow-up period of six months. Ten patients (six girls and four
      boys) with a mean age of 8.1 years (range 2-14 years) with giant hydronephrosis
      caused by primary ureteropelvic junction obstruction underwent a dismembered
      pyeloplasty followed by plication of the dilated renal calyces. The preoperative
      evaluation included an excretory urography, ultrasonography, 99mTc-DMSA and 99mTc
      DTPA scans. The same tests were repeated six months after the operation to
      evaluate the outcomes. There were no intraoperative or postoperative
      complications. Excretory urography and ultrasonography performed six months after
      the operation demonstrated a significant improvement of the morphology of the
      operated kidneys. The kidneys shrunk in diameter from a mean of 149.5 mm (range
      89-224 mm) to 93.6 mm (range 68-121 mm) and the mean diameter of the calyces was
      reduced from 26.9 mm (range 15-42 mm) to 14.7 mm (range 10-24 mm). Renal 99mTc
      DTPA scans showed improved perfusion and renal function after surgery, with the
      mean elimination rate decreasing from 22.41 min (range 17.84 - 28.22 min) to 11.7
      min (range 8.16-13.76 mm). 99mTc-DMSA scans demonstrated no new scars and no
      deterioration of renal parenchyma after surgery. We believe that plication of the
      renal calyces is the method of choice to be used as an adjunct to the Anderson
      Hynes pyeloplasty in the treatment of paediatric patients with giant
      hydronephrosis.

PMID- 16909357
TI  - Sigmoid colon vaginoplasty in children.
AB  - BACKGROUND: Vaginal construction is necessary for the patients with aplasia of
      Mullerian ducts, testicular feminisation and androgen insensitivity syndromes.
      Many methods of vaginal construction have been described. We report here the
      outcomes of six adolescent patients who underwent sigmoid colon vaginoplasty with
      special emphasis on the surgical technique and outcomes. PATIENTS AND METHODS:
      Between 1990 and 2003, six patients underwent sigmoid vaginoplasty after a
      diagnosis of 5alpha-reductase deficiency (n = 3), testicular feminisation (n = 2)
      or vaginal atresia (n = 1). The mean age was 16 years (13 to 18). Wide spectrum
      antibiotics and whole-gut preparation were used in all cases. A 15-20 cm segment
      of sigmoid colon was pulled through the retrovesical tunnel. The proximal end was
      closed in two layers in patients with 5alpha-reductase deficiency and with
      testicular feminisation. A distal anastomosis was carried out to the opening made
      on the vaginal plate (5alpha-reductase deficiency) or on the tip of the shallow
      rudimentary vagina (testicular feminisation). The sigmoid segment was interposed
      between the blind end of the atretic vagina and the perineum in the patient with
      vaginal atresia. Patients were instructed to perform daily vaginal irrigation.
      The neovagina was examined and calibrated under anaesthesia. No routine vaginal
      dilatation was recommended. RESULTS: All but one patient had an uneventful
      postoperative period and were discharged within 7-8 days. All patients had an
      excellent cosmetic result with an appropriate vaginal length. One of the patients
      experienced late stenosis of the introitus which responded to dilatations. Mucus
      discharge was not a significant problem. The patient with vaginal atresia (Bardet
      Biedl syndrome) experienced deep vein thrombosis, renal failure and sepsis,
      resulting in death. CONCLUSION: Sigmoid colon vaginoplasty is a special procedure
      which appears appropriate for the construction of a new vagina in children. A
      sigmoid colon neovagina meets all necessary criteria after a vaginoplasty. It
      provides an adequate diameter and length, and produces less scar tissue in the
      perineum. It is self-moistening, easily adaptable to the uterus, cervix and
      rudimentary atretic vaginal segments and does not require routine dilatation.
      Mild stenosis of the introitus can be treated by dilatations and revision can be
      easily performed in severely stenotic cases. On the other hand, the patient may
      face morbidity after laparotomy and other serious complications may occur due to
      accompanying diseases.

PMID- 16909358
TI  - Is the anorectal sphincter damaged during a transanal endorectal pull-through
      (TERPT) for Hirschsprung's disease? A 3-dimensional, vector manometric
      investigation.
AB  - BACKGROUND/PURPOSE: The transanal endorectal pull-through technique (TERPT) for
      Hirschsprung's disease (HD) exercises considerable traction on the anorectal
      tissue during dissection. So the question arises as to whether TERPT impairs the
      integrity of the anorectal sphincter. Computerised 8-channel vector manometry
      allows a segmental, 360 degrees analysis of muscular defects along the anal
      canal. Such data after TERPT are not available yet. METHODS: Between 2002 and
      2004, 7 children underwent primary TERPT for HD of the rectosigmoid. All could be
      recruited for follow-up examinations. Stooling pattern, rectal examination,
      conventional 4-channel and computerised 8-channel vector manometry were assessed;
      the anal sphincter pressure at rest (ASPR), rectoanal inhibitory reflex (RIR),
      anal canal length (ACL), high pressure zone (HPZ), maximal segmental pressure
      (max SP), segmental/total asymmetric index (SAI/TAI), vector volume at rest (VV)
      were studied. Mean pre- and postoperative values were compared (pre/post).
      RESULTS: After a mean of 14 months (range 3-21 months) all children had
      spontaneous bowel movements, with no complaints of encopresis or constipation. 4
      channel manometry revealed an unchanged ASPR (48.1/49.2 mmHg). RIR was present in
      1/7. Computerised 8-channel comparison revealed no changes for ACL (15.4/16 mm),
      HPZ (60/53.19 % of ACL), SAI (17.6/18.63 %) and TAI (35.8/35.63 %). A
      postoperative increase was noted for max SP squeeze (141.4/178.7 mmHg) and VV (38
      161/46 680 mmHg/cm (2)). In conclusion, the TERPT for HD preserves the functional
      integrity of the anorectal sphincter complex and has a favourable clinical and
      manometric outcome.

PMID- 16909359
TI  - Paediatric paranasal sinus mucoceles.
AB  - Mucoceles of the paranasal sinuses are extremely rare in children and adolescents
      and most cases described in the literature are associated with cystic fibrosis.
      The condition is potentially dangerous but frequently diagnosed late or
      inaccurately due to its non-specific symptoms or to an absence of inflammation
      parameters or other clinical signs. We present 3 children with mucoceles
      (sphenoid sinus n = 2, ethmoid sinus n = 1) in whom cystic fibrosis was
      discounted and who were managed in our medical centre during the last 3 years. No
      aetiological factor was identified in the 2 cases of sphenoid mucocele. The main
      symptom in these two patients was therapy-resistant cephalgia which shifted
      location and varied in intensity. One child had had recurrent sinus infection
      which was a possible aetiological factor of the ethmoidal mucocele. All patients
      successfully underwent endoscopic sinus surgery. During a 2-year follow-up, all
      patients have remained free of symptoms and no mucocele recurrence has been
      observed so far. The rareness of paranasal sinus mucoceles in children, in
      particular its sphenoid occurrence, coupled with its relatively non-specific
      symptomatology prompted the authors to outline and discuss the aetiological
      factors, clinical findings, and therapy and to review the literature.

PMID- 16909360
TI  - Huge intra- and extrathoracic lymphangioma in a baby successfully treated by
      sclerotherapy with OK-432.
AB  - Lymphangiomas are rare congenital malformations of the lymphatic system. They
      typically appear within the first two years of life. They present as soft,
      indolent and benign tumors. As they have a tendency to grow in an infiltrating
      manner and rarely regress spontaneously, treatment may be necessary if the
      lymphangioma's location is functionally and cosmetically disturbing. Surgical
      therapy, which has been the treatment of choice so far, includes a risk of
      complications, depending on the location and extent of the tumor. Therefore
      alternative treatments such as sclerotherapy, especially with OK-432, have been
      developed. We present the case of a female baby with a huge macrocystic
      lymphangioma, extending over one half of the trunk, located intra- and
      extrathoracically, which was treated successfully by surgical resection and
      several intralesional injections of OK-432.

PMID- 16909361
TI  - Congenital segmental fibromuscular hypertrophy of the esophagus and esophageal
      atresia: an uncommon case.
AB  - Although a rare entity, congenital esophageal stenosis due to segmental
      hypertrophy of the muscularis and submucosal layers with diffuse fibrosis should
      be considered a possibility in patients with esophageal stricture associated to
      congenital esophageal atresia. The efficacy of dilatation seems to be limited,
      and may even result in severe complications such as an esophageal rupture.
      Surgical repair for congenital esophageal stenosis is the authors' preferred
      treatment, although initial dilatation may be effective for some patients.

PMID- 16909362
TI  - Bile duct injury complicated by bilioma after blunt liver trauma in a child.
AB  - Nonoperative management with close observation represents the standard of care
      for blunt liver injury, unless vital signs deteriorate or an associated injury
      requires emergency operation. Injuries of the biliary tract remain important
      concomitant lesions following liver trauma. Posttraumatic extraductal biliary
      collections or biliomas are rare complications of blunt abdominal traumas and
      only a few cases have been reported in the pediatric age group. We report a 5
      year-old boy who suffered from blunt abdominal trauma that resulted in liver
      laceration and, eventually, bilioma formation. The patient was managed
      nonoperatively for liver injury. The diagnosis was confirmed by computed
      tomography (CT)-guided needle aspiration and percutaneous catheter drainage,
      which also allowed nonoperative management. The patient was symptom-free with
      normal liver function tests and a normal liver appearance on ultrasound
      examination six months after the accident. The possibility of missed bile duct
      injury should be considered when nonoperative management is used and close
      observation of the patient is necessary over a prolonged period.

PMID- 16909363
TI  - Bannayan-riley-ruvalcaba syndrome from the point of view of the pediatric
      surgeon.
AB  - Bannayan-Riley-Ruvalcaba syndrome (BRRS) is an overgrowth syndrome and polyposis
      condition, which carries an increased risk for development of benign and
      malignant tumors of various tissues and organs. A 9-year-old boy with BRRS who
      had multiple subcutaneous mesenchymal tumors and follicular adenoma of the
      thyroid and a 14-year-old boy with multiple subcutaneous mesenchymal tumors and
      gastrointestinal polyposis are presented, with special emphasis on the surgical
      management of these patients.

PMID- 16909364
TI  - Urethral duplication in association with anorectal malformation.
AB  - Urethral duplication is an uncommon congenital anomaly, not often reported, which
      may be partial or complete. Anorectal malformations are not as uncommon and they
      may be associated with a host of associated anomalies. However, the association
      of urethral duplication with anorectal malformation is rare; this report
      describes two such cases. In one case the intervening septum could be incised
      endoscopically and in the other case the duplicated urethra was excised.

PMID- 16909365
TI  - Pediatric diffuse lipoblastomatosis of the foot -- a case report and review of
      the literature.
AB  - Diffuse lipoblastomatosis is a rare lipomatous tumor of infancy that derives from
      fetal-embryonal fat. It usually affects infants and children and presents as a
      superficial mass that extends from the subcutis to the underlying muscle in the
      upper or lower extremities. In spite of its benign nature, the tumor may behave
      in a locally aggressive manner and invade the surrounding tissues. A case of
      isolated diffuse lipoblastomatosis of a 5-year-old boy in the plantar aspect of
      his right foot that has not been documented in that area before is described. The
      clinical and radiological presentation and histologic evaluation of diffuse
      lipoblastomatosis are discussed, in order to make a differential diagnosis
      between this rare tumor and other soft tissue tumors. In addition, the treatment
      principles of the tumor are described. This case demonstrates that diffuse
      lipoblastomatosis can be difficult to diagnose without histologic evaluation and,
      once diagnosed, should be treated by adequate surgical excision in order to
      prevent recurrence.

PMID- 16909367
TI  - Epidemiology of acute lung injury and acute respiratory distress syndrome.
AB  - Acute respiratory distress syndrome (ARDS) is a heterogeneous disorder that may
      be triggered by myriad etiologies (both pulmonary and extrapulmonary). Mortality
      rates for ARDS range from 30 to 75%, and most deaths are a consequence of
      multiorgan failure (MOF). Since the sentinel description of ARDS in 1967,
      criteria for the diagnosis of this entity were refined. In 1992, diagnostic
      criteria for ARDS were published in an American-European Consensus Conference and
      the term ACUTE LUNG INJURY (ALI) was adopted to encompass patients with a
      spectrum of less severe forms of the same pathological entity. This review
      discusses limitations of various criteria utilized to diagnosis ARDS and ALI, and
      why some criteria may be problematic when designing clinical trials. Also
      discussed are the myriad causes of ARDS, incidence, epidemiology, mortality, and
      factors that influence outcome.

PMID- 16909368
TI  - Pathophysiology of acute lung injury and the acute respiratory distress syndrome.
AB  - Since the adult respiratory distress syndrome was first described substantial
      progress has been made in understanding the pathogenesis of this complex
      syndrome. This review summarizes our current understanding of the pathophysiology
      of what is now termed the acute respiratory distress syndrome (ARDS) and its less
      severe form acute lung injury (ALI), with an emphasis on cellular and molecular
      mechanisms of injury that may represent potential therapeutic targets. Although
      it is difficult to synthesize all of these abnormalities into a single, unified,
      pathogenetic pathway, a theme that emerges repeatedly is that of imbalance, be it
      between pro- and anti-inflammatory cytokines, oxidants and antioxidants,
      procoagulants and anticoagulants, neutrophil recruitment and activation and
      mechanisms of neutrophil clearance, or proteases and protease inhibitors. Future
      therapies aimed at restoring the overall balance of cytokines, oxidants,
      coagulants, and proteases may ultimately be successful where therapies that
      target individual cytokines or other mediators have not.

PMID- 16909369
TI  - The role of cytokines during the pathogenesis of ventilator-associated and
      ventilator-induced lung injury.
AB  - Mortality rates from acute lung injury (ALI)/acute respiratory distress syndrome
      (ARDS) range from 30 to 65%. Although mechanical ventilation (MV) may delay
      mortality in critically ill patients with ALI/ARDS, it may also cause a lung
      injury that further promotes and perpetuates ALI/ARDS and multiorgan dysfunction
      syndrome (MODS). Recent studies have demonstrated that lung protective strategies
      of MV, as compared with the injurious strategy of conventional MV (CMV) can
      reduce absolute mortality rates during ALI/ARDS. The protective strategies limit
      tidal volumes and peak/plateau pressures while maximizing positive end-expiratory
      pressure. The injury to the lung by CMV is characterized histologically by edema,
      leukocyte extravasation, and endothelial and epithelial damage. Both human and
      animal studies suggest that alveolar cell deformation from CMV leads to the
      release of cytokines/chemokines which orchestrate the extravasation, activation,
      and recruitment of leukocytes, causing ventilator-associated lung injury (VALI)
      and ventilator-induced lung injury (VILI). Moreover, VALI/VILI can perpetuate the
      chronic inflammatory response during ALI/ARDS and MODS. This article explores the
      role of cytokines/chemokines during the pathogenesis of VALI/VILI.

PMID- 16909370
TI  - The role of the coagulation cascade in the continuum of sepsis and acute lung
      injury and acute respiratory distress syndrome.
AB  - Sepsis is a common and life-threatening condition with a high mortality rate.
      Severe sepsis includes multiorgan dysfunction syndrome. The organ most often
      affected is the lung, with development of acute lung injury (ALI), which, in its
      most severe form, is referred to as acute respiratory distress syndrome (ARDS).
      Our understanding of inflammation in the pathogenesis of sepsis and ALI is
      continually growing. However, therapies aimed at the inflammatory cascade in
      sepsis have been unsuccessful. These failures have led investigators to consider
      other pathways that may be important in the development of sepsis and ALI,
      including the coagulation and fibrinolytic cascades. In fact, the first therapy
      to reduce mortality in sepsis modulates the coagulation cascade. With this
      clinical success, administration of drotecogin alfa (recombinant activated
      protein C), the importance of coagulation in the pathogenesis of human sepsis is
      becoming clearer. This review summarizes the current understanding of the role of
      coagulation and fibrinolytic abnormalities in sepsis and the development of ALI
      and ARDS. Both in vitro and in vivo studies of the role of the coagulation
      cascade in sepsis and lung injury will be discussed, including initiation of
      coagulation through modulation of tissue factor and tissue factor pathway
      inhibitor, propagation of coagulation via protein C and thrombomodulin,
      inhibition of thrombin generation and resolution through thrombolysis by
      plasminogen activator, and plasminogen activator inhibitor-1.

PMID- 16909371
TI  - The future of surfactant therapy during ALI/ARDS.
AB  - The importance of pulmonary surfactant in maintaining normal lung function, and
      the observations that alterations in endogenous surfactant contribute to the lung
      dysfunction associated with acute lung injury (ALI) and the acute respiratory
      distress syndrome (ARDS), provide a rationale for administering exogenous
      surfactant in this setting. The results of clinical trials have been variable,
      however, in part due to the various surfactant preparations used, the different
      delivery and dosing methods employed, and the types of patients targeted for this
      therapy. Based on the insight gained from these studies, ongoing trials have
      modified these factors to optimize outcome, including one trial that is focusing
      on patients with direct lung insults such as pneumonia and aspiration. The future
      of surfactant therapy may well take advantage of the recently described host
      defense functions of this material. Based on extensive in vitro data as well as
      in vivo animal studies demonstrating the anti-inflammatory and antibacterial
      functions of various surfactant components, administration of surfactant earlier
      in the course of the disease, when lung inflammation is present but before severe
      lung dysfunction occurs, may prove to be optimal. This review discusses both the
      biophysical and host defense functions of surfactant in the context of novel
      therapeutic approaches for patients with ALI/ARDS.

PMID- 16909373
TI  - Ventilatory Management of ALI/ARDS.
AB  - Acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS)
      describe syndromes of diffuse parenchymal lung injury resulting from a variety of
      inflammatory triggers. The pathophysiological consequences include stiff, low
      compliance lungs with impaired gas exchange. Importantly, there is often marked
      heterogeneity of disease. Positive pressure ventilation must therefore not only
      focus on recruiting and ventilating diseased units but must also avoid injuring
      healthy units. To this end, the goals of mechanical ventilatory support of ALI
      and ARDS have shifted over the last decade to providing smaller (and thus less
      injurious) tidal volumes and accepting consequently lower arterial values for
      PaO(2) and the development of respiratory acidosis. This has resulted in
      significant improvements in outcomes. Future developments will need to further
      refine this lung protective concept.

PMID- 16909372
TI  - Genomics of acute lung injury.
AB  - Acute lung injury (ALI) is a complex syndrome involving the interplay of both
      environmental (such as the addition of mechanical ventilation) and genetic
      factors. Clinical models have identified risk factors for development and poor
      outcome but these strategies remain imprecise. To better understand the
      mechanisms of pathogenesis associated with mechanisms of ALI, candidate genes
      identified by global expression profiling or related literature searches are
      being explored for relevant polymorphisms (single base pair substitutions) that
      can affect both ALI susceptibility and outcome. This article summarizes several
      specific genetic association studies that have been conducted in ALI and reviews
      supporting data from in vitro and in vivo models of the disease and clinical
      observations. Although valuable information has been reported to date, intense
      analyses are needed in this developing discipline to assure significant clinical
      utility. The detailing of specific associated polymorphisms will continue to
      provide new insights in the understanding of disease pathogenesis, and promise to
      reveal novel molecular targets and personalized treatments to prevent the
      disease.

PMID- 16909374
TI  - Radiological imaging in acute lung injury and acute respiratory distress
      syndrome.
AB  - Computed tomography (CT) has been utilized to study acute respiratory distress
      syndrome (ARDS) since the middle 1980s, when it revealed the inhomogeneous
      pattern of the lung lesion. Its advantages rely on the strict correlation between
      CT density and the lung physical density, allowing a quantification of lung
      compartments with different degrees of aeration. By CT scans, ARDS lung appeared
      to be "small" rather than "stiff," leading to the "baby lung" concept. The
      regional analysis revealed that this appearance derives from an evenly
      distributed lung edema, which tends, because of gravitational forces, to lie
      predominantly in the most dependent regions, leading to alveolar collapse. New
      data suggest that such a "sponge lung" is made by a "core," consolidated, lung
      portion, from which, through an inflammatory reaction, lung edema will spread,
      determining the collapsed and recruitable lung portion. The amount of recruitable
      lung varies among ARDS patients. This knowledge is necessary for a rational
      positive end-expiratory pressure (PEEP) setting because the amount of tissue
      maintained aerated by PEEP is closely associated with the amount of recruitable
      lung. CT scans may also help to diagnose ARDS because CT provides a good estimate
      of the high-permeability lung edema, the characteristic lesion of this syndrome.

PMID- 16909375
TI  - Acute lung injury and acute respiratory distress syndrome: extracorporeal life
      support and liquid ventilation for severe acute respiratory distress syndrome in
      adults.
AB  - Acute respiratory distress syndrome (ARDS) has many underlying causes and carries
      an overall mortality of 40 to 60%. For those patients with severe ARDS who have a
      predicted mortality of 80 to 100%, extracorporeal life support (ECLS) can provide
      an extraordinary means of support. We recently demonstrated a survival to
      hospital discharge of 52% in this subset of patients. ECLS is capable of
      providing full respiratory and cardiac support, allowing time for the patient to
      recover from the underlying disease process. Additionally, ventilator settings
      are reduced to "rest" settings, avoiding the consequences of ventilator-induced
      lung injury that can contribute to a worse outcome. Systemic heparinization is a
      mainstay of ECLS therapy because of platelet activation in the circuit.
      Mechanical complications and significant bleeding can occur in up to one quarter
      of patients, requiring close attention and prompt intervention should they occur.
      Although not currently in clinical practice, liquid ventilation using
      perfluorocarbons to provide gas exchange in the lungs is a potentially useful
      adjunct in the management of severe respiratory failure.

PMID- 16909376
TI  - Treatment of acute lung injury: historical perspective and potential future
      therapies.
AB  - The acute respiratory distress syndrome (ARDS) was first described by Ashbaugh
      and colleagues in 1967. However, despite considerable efforts, early progress in
      treatment was slowed by lack of consistent definitions and appropriately powered
      clinical trials. In 1994, the American-European Consensus Conference on ARDS
      established criteria defining ARDS as well as acute lung injury (ALI).
      Additionally, the conference established research directives and international
      coordination of clinical studies. Current incidence of ALI in the United States
      is estimated at 200,000 cases per year with a mortality rate approaching 40%.
      Mechanical ventilation, using positive end-expiratory pressure and reduced tidal
      volumes and inspiratory pressures, along with improved supportive care has
      increased survival rates. However, to date, pharmacological therapies have failed
      to improve survival in multicenter clinical trials. This article focuses on
      clinical treatments for ALI that have been tested in phase II and III clinical
      trials as well as a discussion of potential future therapies.

PMID- 16909377
TI  - 2005 William Allan Award address. Introductory speech for Francis S. Collins.

PMID- 16909378
TI  - 2005 William Allan Award address. No longer just looking under the lamppost.

PMID- 16909379
TI  - 2005 Curt Stern Award address. Introductory speech for Patrick O. Brown.

PMID- 16909380
TI  - 2005 Curt Stern Award address. Exploring along a crooked path.

PMID- 16909381
TI  - Medical genetics in the genomic medicine of the 21st century.

PMID- 16909382
TI  - A chromosome 8 gene-cluster polymorphism with low human beta-defensin 2 gene copy
      number predisposes to Crohn disease of the colon.
AB  - Defensins are endogenous antimicrobial peptides that protect the intestinal
      mucosa against bacterial invasion. It has been suggested that deficient defensin
      expression may underlie the chronic inflammation of Crohn disease (CD). The DNA
      copy number of the beta-defensin gene cluster on chromosome 8p23.1 is highly
      polymorphic within the healthy population, which suggests that the defective beta
      defensin induction in colonic CD could be due to low beta-defensin-gene copy
      number. Here, we tested this hypothesis, using genomewide DNA copy number
      profiling by array-based comparative genomic hybridization and quantitative
      polymerase-chain-reaction analysis of the human beta-defensin 2 (HBD-2) gene. We
      showed that healthy individuals, as well as patients with ulcerative colitis,
      have a median of 4 (range 2-10) HBD-2 gene copies per genome. In a surgical
      cohort with ileal or colonic CD and in a second large cohort with inflammatory
      bowel diseases, those with ileal resections/disease exhibited a normal median HBD
      2 copy number of 4, whereas those with colonic CD had a median of only 3 copies
      per genome (P=.008 for the surgical cohort; P=.032 for the second cohort).
      Overall, the copy number distribution in colonic CD was shifted to lower numbers
      compared with controls (P=.002 for both the surgical cohort and the cohort with
      inflammatory bowel diseases). Individuals with < or = 3 copies have a
      significantly higher risk of developing colonic CD than did individuals with > or
      = 4 copies (odds ratio 3.06; 95% confidence interval 1.46-6.45). An HBD-2 gene
      copy number of < 4 was associated with diminished mucosal HBD-2 mRNA expression
      (P=.033). In conclusion, a lower HBD-2 gene copy number in the beta-defensin
      locus predisposes to colonic CD, most likely through diminished beta-defensin
      expression.

PMID- 16909383
TI  - A new autosomal recessive form of Stickler syndrome is caused by a mutation in
      the COL9A1 gene.
AB  - Stickler syndrome is characterized by ophthalmic, articular, orofacial, and
      auditory manifestations. It has an autosomal dominant inheritance pattern and is
      caused by mutations in COL2A1, COL11A1, and COL11A2. We describe a family of
      Moroccan origin that consists of four children with Stickler syndrome, six
      unaffected children, and two unaffected parents who are distant relatives (fifth
      degree). All family members were clinically investigated for ear, nose, and
      throat; ophthalmologic; and radiological abnormalities. Four children showed
      symptoms characteristic of Stickler syndrome, including moderate-to-severe
      sensorineural hearing loss, moderate-to-high myopia with vitreoretinopathy, and
      epiphyseal dysplasia. We considered the COL9A1 gene, located on chromosome 6q13,
      to be a candidate gene on the basis of the structural association with collagen
      types II and XI and because of the high expression in the human inner ear
      indicated by cDNA microarray. Mutation analysis of the coding region of the
      COL9A1 gene showed a homozygous R295X mutation in the four affected children. The
      parents and four unaffected children were heterozygous carriers of the R295X
      mutation. Two unaffected children were homozygous for the wild-type allele. None
      of the family members except the homozygous R295X carriers had any signs of
      Stickler syndrome. Therefore, COL9A1 is the fourth identified gene that can cause
      Stickler syndrome. In contrast to the three previously reported Stickler syndrome
      causing genes, this gene causes a form of Stickler syndrome with an autosomal
      recessive inheritance pattern. This finding will have a major impact on the
      genetic counseling of patients with Stickler syndrome and on the understanding of
      the pathophysiology of collagens. Mutation analysis of this gene is recommended
      in patients with Stickler syndrome with possible autosomal recessive inheritance.

PMID- 16909384
TI  - The value of molecular haplotypes in a family-based linkage study.
AB  - Novel methods that could improve the power of conventional methods of gene
      discovery for complex diseases should be investigated. In a simulation study, we
      aimed to investigate the value of molecular haplotypes in the context of a family
      based linkage study. The term "haplotype" (or "haploid genotype") refers to
      syntenic alleles inherited on a single chromosome, and we use the term "molecular
      haplotype" to refer to haplotypes that have been determined directly by use of a
      molecular technique such as long-range allele-specific polymerase chain reaction.
      In our study, we simulated genotype and phenotype data and then compared the
      powers of analyzing these data under the assumptions that various levels of
      information from molecular haplotypes were available. (This information was
      available because of the simulation procedure.) Several conclusions can be drawn.
      First, as expected, when genetic homogeneity is expected or when marker data are
      complete, it is not efficient to generate molecular haplotyping information.
      However, with levels of heterogeneity and missing data patterns typical of
      complex diseases, we observed a 23%-77% relative increase in the power to detect
      linkage in the presence of heterogeneity with heterogeneity LOD scores >3.0 when
      all individuals are molecularly haplotyped (compared with the power when only
      standard genotypes are used). Furthermore, our simulations indicate that most of
      the increase in power can be achieved by molecularly haplotyping a single
      individual in each family, thereby making molecular haplotyping a valuable
      strategy for increasing the power of gene mapping studies of complex diseases.
      Maximization of power, given an existing family set, can be particularly
      important for late-onset, often-fatal diseases such as cancer, for which
      informative families are difficult to collect.

PMID- 16909385
TI  - Mitochondrial DNA-deletion mutations accumulate intracellularly to detrimental
      levels in aged human skeletal muscle fibers.
AB  - Skeletal muscle-mass loss with age has severe health consequences, yet the
      molecular basis of the loss remains obscure. Although mitochondrial DNA (mtDNA)
      deletion mutations have been shown to accumulate with age, for these aberrant
      genomes to be physiologically relevant, they must accumulate to high levels
      intracellularly and be present in a significant number of cells. We examined
      mtDNA-deletion mutations in vastus lateralis (VL) muscle of human subjects aged
      49-93 years, using both histologic and polymerase-chain-reaction (PCR) analyses,
      to determine the physiological and genomic integrity of mitochondria in aging
      human muscle. The number of VL muscle fibers exhibiting mitochondrial electron
      transport-system (ETS) abnormalities increased from an estimated 6% at age 49
      years to 31% at age 92 years. We analyzed the mitochondrial genotype of 48 single
      ETS-abnormal, cytochrome c oxidase-negative/succinate dehydrogenase-hyperreactive
      (COX-/SDH++) fibers from normal aging human subjects and identified mtDNA
      deletion mutations in all abnormal fibers. Deletion mutations were clonal within
      a fiber and concomitant to the COX-/SDH++ region. Quantitative PCR analysis of
      wild-type and deletion-containing mtDNA genomes within ETS-abnormal regions of
      single fibers demonstrated that these deletion mutations accumulate to
      detrimental levels (>90% of the total mtDNA).

PMID- 16909386
TI  - A fast method for computing high-significance disease association in large
      population-based studies.
AB  - Because of rapid progress in genotyping techniques, many large-scale, genomewide
      disease-association studies are now under way. Typically, the disorders examined
      are multifactorial, and, therefore, researchers seeking association must consider
      interactions among loci and between loci and other factors. One of the challenges
      of large disease-association studies is obtaining accurate estimates of the
      significance of discovered associations. The linkage disequilibrium between SNPs
      makes the tests highly dependent, and dependency worsens when interactions are
      tested. The standard way of assigning significance (P value) is by a permutation
      test. Unfortunately, in large studies, it is prohibitively slow to compute low P
      values by this method. We present here a faster algorithm for accurately
      calculating low P values in case-control association studies. Unlike with several
      previous methods, we do not assume a specific distribution of the traits, given
      the genotypes. Our method is based on importance sampling and on accounting for
      the decay in linkage disequilibrium along the chromosome. The algorithm is
      dramatically faster than the standard permutation test. On data sets mimicking
      medium-to-large association studies, it speeds up computation by a factor of
      5,000-100,000, sometimes reducing running times from years to minutes. Thus, our
      method significantly increases the problem-size range for which accurate,
      meaningful association results are attainable.

PMID- 16909387
TI  - X chromosome-inactivation patterns of 1,005 phenotypically unaffected females.
AB  - X-chromosome inactivation is widely believed to be random in early female
      development and to result in a mosaic distribution of cells, approximately half
      with the paternally derived X chromosome inactive and half with the maternally
      derived X chromosome inactive. Significant departures from such a random pattern
      are hallmarks of a variety of clinical states, including being carriers for
      severe X-linked diseases or X-chromosome cytogenetic abnormalities. To evaluate
      the significance of skewed patterns of X inactivation, we examined patterns of X
      inactivation in a population of >1,000 phenotypically unaffected females. The
      data demonstrate that only a very small proportion of unaffected females show
      significantly skewed inactivation, especially during the neonatal period. By
      comparison with this data set, the degree of skewed inactivation in a given
      individual can now be quantified and evaluated for its potential clinical
      significance.

PMID- 16909388
TI  - Oligonucleotide microarray analysis of genomic imbalance in children with mental
      retardation.
AB  - The cause of mental retardation in one-third to one-half of all affected
      individuals is unknown. Microscopically detectable chromosomal abnormalities are
      the most frequently recognized cause, but gain or loss of chromosomal segments
      that are too small to be seen by conventional cytogenetic analysis has been found
      to be another important cause. Array-based methods offer a practical means of
      performing a high-resolution survey of the entire genome for submicroscopic copy
      number variants. We studied 100 children with idiopathic mental retardation and
      normal results of standard chromosomal analysis, by use of whole-genome sampling
      analysis with Affymetrix GeneChip Human Mapping 100K arrays. We found de novo
      deletions as small as 178 kb in eight cases, de novo duplications as small as 1.1
      Mb in two cases, and unsuspected mosaic trisomy 9 in another case. This
      technology can detect at least twice as many potentially pathogenic de novo copy
      number variants as conventional cytogenetic analysis can in people with mental
      retardation.

PMID- 16909389
TI  - Molecular characterization of loss-of-function mutations in PCSK9 and
      identification of a compound heterozygote.
AB  - Elevated levels of circulating low-density lipoprotein cholesterol (LDL-C) play a
      central role in the development of atherosclerosis. Mutations in proprotein
      convertase subtilisin/kexin type 9 (PCSK9) that are associated with lower plasma
      levels of LDL-C confer protection from coronary heart disease. Here, we show that
      four severe loss-of-function mutations prevent the secretion of PCSK9 by
      disrupting synthesis or trafficking of the protein. In contrast to recombinant
      wild-type PCSK9, which was secreted from cells into the medium within 2 hours,
      the severe loss-of-function mutations in PCSK9 largely abolished PCSK9 secretion.
      This finding predicted that circulating levels of PCSK9 would be lower in
      individuals with the loss-of-function mutations. Immunoprecipitation and
      immunoblotting of plasma for PCSK9 provided direct evidence that the serine
      protease is present in the circulation and identified the first known individual
      who has no immunodetectable circulating PCSK9. This healthy, fertile college
      graduate, who was a compound heterozygote for two inactivating mutations in
      PCSK9, had a strikingly low plasma level of LDL-C (14 mg/dL). The very low plasma
      level of LDL-C and apparent good health of this individual demonstrate that PCSK9
      plays a major role in determining plasma levels of LDL-C and provides an
      attractive target for LDL-lowering therapy.

PMID- 16909390
TI  - Meiotic recombination and spatial proximity in the etiology of the recurrent
      t(11;22).
AB  - Although balanced translocations are among the most common human chromosomal
      aberrations, the constitutional t(11;22)(q23;q11) is the only known recurrent non
      Robertsonian translocation. Evidence indicates that de novo formation of the
      t(11;22) occurs during meiosis. To test the hypothesis that spatial proximity of
      chromosomes 11 and 22 in meiotic prophase oocytes and spermatocytes plays a role
      in the rearrangement, the positions of the 11q23 and 22q11 translocation
      breakpoints were examined. Fluorescence in situ hybridization with use of DNA
      probes for these sites demonstrates that 11q23 is closer to 22q11 in meiosis than
      to a control at 6q26. Although chromosome 21p11, another control, often lies as
      close to 11q23 as does 22q11 during meiosis, chromosome 21 rarely rearranges with
      11q23, and the DNA sequence of chromosome 21 appears to be less susceptible than
      22q11 to double-strand breaks (DSBs). It has been suggested that the
      rearrangement recurs as a result of the palindromic AT-rich repeats at both 11q23
      and 22q11, which extrude hairpin structures that are susceptible to DSBs. To
      determine whether the DSBs at these sites coincide with normal hotspots of
      meiotic recombination, immunocytochemical mapping of MLH1, a protein involved in
      crossing over, was employed. The results indicate that the translocation
      breakpoints do not coincide with recombination hotspots and therefore are
      unlikely to be the result of meiotic programmed DSBs, although MRE11 is likely to
      be involved. Previous analysis indicated that the DSBs appear to be repaired by a
      mechanism similar to nonhomologous end joining (NHEJ), although NHEJ is normally
      suppressed during meiosis. Taken together, these studies support the hypothesis
      that physical proximity between 11q23 and 22q11--but not typical meiotic
      recombinational activity in meiotic prophase--plays an important role in the
      generation of the constitutional t(11;22) rearrangement.

PMID- 16909391
TI  - An expectation-maximization algorithm for the analysis of allelic expression
      imbalance.
AB  - A significant proportion of the variation between individuals in gene expression
      levels is genetic, and it is likely that these differences correlate with
      phenotypic differences or with risk of disease. Cis-acting polymorphisms are
      important in determining interindividual differences in gene expression that lead
      to allelic expression imbalance, which is the unequal expression of homologous
      alleles in individuals heterozygous for such a polymorphism. This expression
      imbalance can be detected using a transcribed polymorphism, and, once it is
      established, the next step is to identify the polymorphisms that are responsible
      for or predictive of allelic expression levels. We present an expectation
      maximization algorithm for such analyses, providing a formal statistical
      framework to test whether a candidate polymorphism is associated with allelic
      expression differences.

PMID- 16909392
TI  - Navajo neurohepatopathy is caused by a mutation in the MPV17 gene.
AB  - Navajo neurohepatopathy (NNH) is an autosomal recessive disease that is prevalent
      among Navajo children in the southwestern United States. The major clinical
      features are hepatopathy, peripheral neuropathy, corneal anesthesia and scarring,
      acral mutilation, cerebral leukoencephalopathy, failure to thrive, and recurrent
      metabolic acidosis with intercurrent infections. Infantile, childhood, and
      classic forms of NNH have been described. Mitochondrial DNA (mtDNA) depletion was
      detected in the livers of two patients, suggesting a primary defect in mtDNA
      maintenance. Homozygosity mapping of two families with NNH suggested linkage to
      chromosome 2p24. This locus includes the MPV17 gene, which, when mutated, causes
      a hepatocerebral form of mtDNA depletion. Sequencing of the MPV17 gene in six
      patients with NNH from five families revealed the homozygous R50Q mutation
      described elsewhere. Identification of a single missense mutation in patients
      with NNH confirms that the disease is probably due to a founder effect and
      extends the phenotypic spectrum associated with MPV17 mutations.

PMID- 16909393
TI  - UBE2A, which encodes a ubiquitin-conjugating enzyme, is mutated in a novel X
      linked mental retardation syndrome.
AB  - We report a mutation of UBE2A/HR6A, which encodes a ubiquitin-conjugating enzyme
      (E2), a member of the ubiquitin proteasome pathway, as the cause of a novel X
      linked mental retardation (XLMR) syndrome that affects three males in a two
      generation family. A single-nucleotide substitution, c.382C-->T in UBE2A, led to
      a premature UAG stop codon (Q128X). As a consequence, the predicted polypeptide
      lacks the 25 C-terminal amino acid residues. The importance of this terminal
      sequence for UBE2 function is inferred by its conservation in vertebrates and in
      Drosophila. UBE2A mutations do not appear to significantly contribute to XLMR,
      since no UBE2A mutations were identified in 15 families with nonsyndromic and 4
      families with syndromic idiopathic XLMR previously mapped to intervals
      encompassing this gene. This is the first description of a mutation in a
      ubiquitin-conjugating enzyme gene as the cause of a human disease.

PMID- 16909394
TI  - Mutations in the CEP290 (NPHP6) gene are a frequent cause of Leber congenital
      amaurosis.
AB  - Leber congenital amaurosis (LCA) is one of the main causes of childhood
      blindness. To date, mutations in eight genes have been described, which together
      account for approximately 45% of LCA cases. We localized the genetic defect in a
      consanguineous LCA-affected family from Quebec and identified a splice defect in
      a gene encoding a centrosomal protein (CEP290). The defect is caused by an
      intronic mutation (c.2991+1655A-->G) that creates a strong splice-donor site and
      inserts a cryptic exon in the CEP290 messenger RNA. This mutation was detected in
      16 (21%) of 76 unrelated patients with LCA, either homozygously or in combination
      with a second deleterious mutation on the other allele. CEP290 mutations
      therefore represent one of the most frequent causes of LCA identified so far.

PMID- 16909395
TI  - Peters Plus syndrome is caused by mutations in B3GALTL, a putative
      glycosyltransferase.
AB  - Peters Plus syndrome is an autosomal recessive disorder characterized by anterior
      eye-chamber abnormalities, disproportionate short stature, and developmental
      delay. After detection of a microdeletion by array-based comparative genomic
      hybridization, we identified biallelic truncating mutations in the beta 1,3
      galactosyltransferase-like gene (B3GALTL) in all 20 tested patients, showing that
      Peters Plus is a monogenic, primarily single-mutation syndrome. This finding is
      expected to put Peters Plus syndrome on the growing list of congenital
      malformation syndromes caused by glycosylation defects.

PMID- 16909396
TI  - Monte Carlo pedigree disequilibrium test for markers on the X chromosome.
AB  - Because of the need for fine mapping of disease loci and the availability of
      dense single-nucleotide-polymorphism markers, many forms of association tests
      have been developed. Most of them are applicable only to triads, whereas some are
      amenable to nuclear families (sibships). Although there are a number of methods
      that can deal with extended families (e.g., the pedigree disequilibrium test
      [PDT]), most of them cannot accommodate incomplete data. Furthermore, despite a
      large body of literature on association mapping, only a very limited number of
      publications are applicable to X-chromosomal markers. In this report, we first
      extend the PDT to markers on the X chromosome for testing linkage disequilibrium
      in the presence of linkage. This method is applicable to any pedigree structure
      and is termed "X-chromosomal pedigree disequilibrium test" (XPDT). We then
      further extend the XPDT to accommodate pedigrees with missing genotypes in some
      of the individuals, especially founders. Monte Carlo (MC) samples of the missing
      genotypes are generated and used to calculate the XMCPDT (X-chromosomal MC PDT)
      statistic, which is defined as the conditional expectation of the XPDT statistic
      given the incomplete (observed) data. This MC version of the XPDT remains a valid
      test for association under linkage with the assumption that the pedigrees and
      their associated affection patterns are drawn randomly from a population of
      pedigrees with at least one affected offspring. This set of methods was compared
      with existing approaches through simulation, and substantial power gains were
      observed in all settings considered, with type I error rates closely tracking
      their nominal values.

PMID- 16909397
TI  - Mutations in the gene KCNV2 encoding a voltage-gated potassium channel subunit
      cause "cone dystrophy with supernormal rod electroretinogram" in humans.
AB  - "Cone dystrophy with supernormal rod electroretinogram (ERG)" is an autosomal
      recessive disorder that causes lifelong visual loss combined with a supernormal
      ERG response to a bright flash of light. We have linked the disorder to a 0.98-cM
      (1.5-Mb) region on chromosome 9p24, flanked by rs1112534 and rs1074449, using
      homozygosity mapping in one large consanguineous pedigree. Analysis of one gene
      within this region, KCNV2, showed a homozygous nonsense mutation. Mutations were
      also found in 17 alleles of 10 other unrelated families with the same disorder.
      In situ hybridization demonstrated KCNV2 expression in human rod and cone
      photoreceptors. The precise function of KCNV2 in human photoreceptors remains to
      be determined, although this work suggests that mutations might perturb or
      abrogate I(KX), the potassium current within vertebrate photoreceptor inner
      segments, which has been shown to set their resting potential and voltage
      response.

PMID- 16909398
TI  - Genomewide scan for nonsyndromic cleft lip and palate in multigenerational Indian
      families reveals significant evidence of linkage at 13q33.1-34.
AB  - Nonsyndromic cleft lip with or without cleft palate (CL-P) is a common congenital
      anomaly with incidence ranging from 1 in 300 to 1 in 2,500 live births. We
      analyzed two Indian pedigrees (UR017 and UR019) with isolated, nonsyndromic CL-P,
      in which the anomaly segregates as an autosomal dominant trait. The phenotype was
      variable, ranging from unilateral to bilateral CL-P. A genomewide linkage scan
      that used approximately 10,000 SNPs was performed. Nonparametric linkage (NPL)
      analysis identified 11 genomic regions (NPL>3.5; P<.005) that could potentially
      harbor CL-P susceptibility variations. Among those, the most significant evidence
      was for chromosome 13q33.1-34 at marker rs1830756 (NPL=5.57; P=.00024). This was
      also supported by parametric linkage; MOD score (LOD scores maximized over
      genetic model parameters) analysis favored an autosomal dominant model. The
      maximum LOD score was 4.45, and heterogeneity LOD was 4.45 (alpha =100%).
      Haplotype analysis with informative crossovers enabled the mapping of the CL-P
      locus to a region of approximately 20.17 cM (7.42 Mb) between SNPs rs951095 and
      rs726455. Thus, we have identified a novel genomic region on 13q33.1-34 that
      harbors a high-risk variant for CL-P in these Indian families.

PMID- 16909399
TI  - Schizophrenia and oxidative stress: glutamate cysteine ligase modifier as a
      susceptibility gene.
AB  - Oxidative stress could be involved in the pathophysiology of schizophrenia, a
      major psychiatric disorder. Glutathione (GSH), a redox regulator, is decreased in
      patients' cerebrospinal fluid and prefrontal cortex. The gene of the key GSH
      synthesizing enzyme, glutamate cysteine ligase modifier (GCLM) subunit, is
      strongly associated with schizophrenia in two case-control studies and in one
      family study. GCLM gene expression is decreased in patients' fibroblasts. Thus,
      GSH metabolism dysfunction is proposed as one of the vulnerability factors for
      schizophrenia.

PMID- 16909402
TI  - Women's interpretation of an abnormal result on measurement of fetal nuchal
      translucency and maternal serum screening for prenatal testing of Down syndrome.
AB  - OBJECTIVE: To assess the effects of sociodemographic and health-provider factors
      on women's understanding of abnormal results on measurement of nuchal
      translucency (NT) and maternal serum screening (MSS), 18 months after the
      implementation of a policy aimed at increasing women's awareness regarding MSS.
      METHODS: A representative sample of women (n = 734) who gave birth in Parisian
      maternity units in 1999 were asked about their understanding of an abnormal
      result on MSS and NT. We assessed the effects of sociodemographic and health
      provider factors on the probability of women interpreting an abnormal result
      correctly, misinterpreting it as a definitive diagnosis, or declaring that they
      did not know how to interpret the result. Response rate was 92% and the analyses
      included multinomial models. RESULTS: For both MSS and NT measurement, the
      majority of women interpreted an abnormal result correctly. However, there were
      substantial sociodemographic differences in the probability of women interpreting
      an abnormal result correctly, and more so in the probability of their declaring
      not to know how to interpret the result. The probability of correct
      interpretations was substantially higher, and that of declaring not to know how
      to interpret the result substantially lower, for MSS than NT measurement.
      However, for several sociodemographic groups, the proportion of women who
      misinterpreted an abnormal result on screening as indicative of a definitive
      diagnosis was also higher for MSS as compared with NT measurement. CONCLUSIONS:
      These findings underscore the need for additional efforts, along with alternative
      strategies, to inform women about the implications of prenatal screening,
      particularly in the case of measurement of NT.

PMID- 16909400
TI  - Deletion of PTEN and BMPR1A on chromosome 10q23 is not always associated with
      juvenile polyposis of infancy.

PMID- 16909403
TI  - The effects on maternal anxiety of two-dimensional versus two- plus three-/four
      dimensional ultrasound in pregnancies at risk of fetal abnormalities: A
      randomized study.
AB  - OBJECTIVE: To test the hypothesis that the use of two-dimensional (2D)
      ultrasonography with three-dimensional/four-dimensional (3D/4D) ultrasonography
      can reduce anxiety to a greater extent in women at risk of having a fetus with
      congenital abnormalities than the use of 2D ultrasonography alone. METHODS: A
      total of 124 women attending the prenatal diagnostic clinic of a teaching
      hospital were randomized into the intervention group (2D ultrasonography followed
      by 3D/4D ultrasonography) or control group (2D ultrasonography alone). The
      primary outcome was maternal anxiety levels, which were assessed by the
      Spielberger state-trait anxiety inventory. We measured the anxiety levels in all
      women at the first visit, at around 18 weeks' gestation (immediately after
      ultrasound examinations) and at 28 weeks' gestation. RESULTS: A short-term
      reduction of the state-anxiety score (by around 2 points) from the first visit to
      after ultrasound examinations was observed in both the intervention group and the
      control group. Unexpectedly, a small increase in the state-anxiety score from the
      first visit to 28 weeks' gestation was observed in the intervention group but not
      in the control group, though there was no significant difference in the changes
      between the two groups. Repeated measures ANOVA (analysis of variance) also
      showed that there was no significant interaction effect between groups and time
      of assessment on the state-anxiety scores (F = 1.072 and P = 0.344). About 80% of
      women reported a better understanding that their baby was normal after viewing 3D
      rather than 2D images. CONCLUSION: This randomized study indicates that the
      addition of 3D/4D ultrasound does not cause a significant reduction in maternal
      anxiety in pregnancies at risk of fetal abnormalities compared with conventional
      2D ultrasound alone.

PMID- 16909404
TI  - It can take 10 days for the right fetal ventricle to recover after a temporary
      closure of the ductus arteriosus.

PMID- 16909405
TI  - Prenatal diagnosis of congenital left ventricular aneurysm by four-dimensional
      ultrasonography with spatio-temporal image correlation (STIC).

PMID- 16909407
TI  - Re: A new strategy for prenatal diagnosis of homozygous alpha0-thalassemia.

PMID- 16909408
TI  - Re: Feasibility and reproducibility of an image-scoring method for quality
      control of fetal biometry in the second trimester.

PMID- 16909409
TI  - Imaging of the cervix using sonoelastography.

PMID- 16909411
TI  - Re: Three-dimensional transperineal ultrasonography for evaluation of the anal
      sphincter complex: Another dimension in understanding peripartum sphincter
      trauma.

PMID- 16909412
TI  - Distinct telomere length regulation in premalignant cervical and endometrial
      lesions: implications for the roles of telomeres in uterine carcinogenesis.
AB  - Mouse models show that progressive shortening of telomeres with ageing causes
      chromosomal instability, which can lead to the initiation of cancer. However, it
      is unclear what roles telomere shortening plays in human carcinogenesis. The
      present study has investigated the involvement of telomere dynamics in uterine
      carcinogenesis. Using telomere-FISH (telo-FISH) assays, telomere lengths in
      premalignant and malignant cervical and endometrial lesions were measured and
      compared with chromosomal arm loss or gain. Telo-FISH signals were visualized
      with Cy3-labelled telomere-specific probes and presented as telomere intensity
      (TI). Early-stage cervical intraepithelial neoplasias (CINs), especially CIN2,
      had significantly shorter telomeres than corresponding normal squamous epithelia
      (p = 0.019), together with increased rates of chromosomal arm loss/gain (p <
      0.001). Cervical cancers had relatively short telomeres, but they also showed
      greater heterogeneity than other sampled tissues, including those with long
      telomeres. In contrast, there was no significant difference between the telomere
      length of normal endometrium and of endometrial hyperplasia and endometrial
      cancer. There was no significant difference in the rate of chromosomal arm
      loss/gain between normal endometrium and endometrial hyperplasia. These findings
      suggest that progressive shortening of telomeres occurs in CIN, in association
      with chromosomal instability, which may play critical roles in cervical
      carcinogenesis. In contrast, endometrial hyperplasias have relatively stable
      telomeres without widespread chromosome alteration, implying that endometrial
      carcinogenesis involves mechanisms distinct from those of cervical
      carcinogenesis, possibly including microsatellite instability.

PMID- 16909413
TI  - The incidence and mortality of cutaneous melanoma in Southern Germany: trends by
      anatomic site and pathologic characteristics, 1976 to 2003.
AB  - BACKGROUND: Cutaneous melanoma (CM) incidence and mortality have risen
      dramatically during the past 2 generations, particularly among Caucasian
      populations. Detailed, long-term trends of CM in relation to clinical and
      pathologic characteristics in a Central European population have not been
      published to date. METHODS: The current study was based on 1980 patients with
      invasive CM diagnosed in Southern Germany during the years from 1976 to 2003
      documented by the Central Malignant Melanoma Registry. The German standard
      population was used to calculate age-standardized rates, and the annual percent
      change was estimated by using age, anatomic site, histologic type, and tumor
      thickness. RESULTS: During the study period, the incidence of CM approximately
      was tripled for males and females, reaching 10.3 and 13.3 per 100,000 per year,
      respectively (P < .001). The largest increases occurred for melanoma localized on
      the upper limbs (annual change, 5.9% for males and 5.0% for females; P < .001)
      and superficially spreading melanoma (annual change, 7.8% for males and 5.9% for
      females; P < .001). Thin tumors (Breslow thickness <1 mm) were presented
      significantly more often during the study period (annual change, 9.8% for males
      and 6.1% for females; P < .001), predominantly in younger patients. Thick tumors
      and nodular melanomas were more frequent among older patients (age >70 years),
      particularly among males. The age-standardized mortality decreased from 1.5 to
      0.8 per 100,000 males and from 2.6 to 0.8 per 100,000 females with a significant
      downward trend for the female population (P < .001). CONCLUSIONS: The current
      results indicated which diverging trends between incidence and mortality may be
      explained by improved public awareness regarding suspicious pigmented lesions and
      the earlier detection of these tumors. Continuation of the current preventive
      strategy and its expansion to include older age groups in the population are
      warranted.

PMID- 16909414
TI  - Phase I study of capecitabine in combination with temozolomide in the treatment
      of patients with brain metastases from breast carcinoma.
AB  - BACKGROUND: A single-institution Phase I clinical trial was conducted to
      determine the maximum tolerated dose (MTD) and define the safety profile of
      temozolomide and capecitabine when used in combination to treat brain metastases
      from breast cancer. METHODS: Patients were eligible if they had bidimensionally
      measurable supratentorial or infratentorial brain metastasis from histologically
      confirmed breast carcinoma. Patients could have received up to 3 prior
      chemotherapy regimens. Temozolomide and capecitabine were administered
      concomitantly to 4 sequential cohorts at different dosing levels on Days 1-5 and
      Days 8-12, with cycles repeated every 21 days until disease progression. RESULTS:
      Twenty-four patients with multiple brain lesions were treated, including 14
      patients with newly diagnosed brain metastases and 10 patients with recurrent
      brain metastases. Only 1 patient was chemotherapy-naive. Fatigue and nausea were
      the most commonly observed toxicities observed at any dose levels. Significant
      antitumor activity was observed, with a total of 1 complete and 3 partial
      responses (18% objective response rate) in the brain. The median response
      duration was 8 weeks (range, 6-64 weeks) and the median time to progression in
      the brain was 12 weeks (range, 3-70 weeks). Neurocognitive function improved or
      remained stable in patients with a response or stable disease. CONCLUSIONS: The
      combination of temozolomide and capecitabine is an active, well-tolerated
      regimen. The observed antitumor activity warrants further evaluation of this
      combination as an alternative to or in combination with whole-brain radiation
      therapy for the treatment of multiple brain metastases.

PMID- 16909415
TI  - Oral outpatient chemotherapy medication errors in children with acute
      lymphoblastic leukemia.
AB  - BACKGROUND: Although medication errors are 1 of the most common types of medical
      errors, their frequency in pediatric patients receiving oral outpatient
      chemotherapeutic agents is unknown. The prescribing, dispensing, and parental
      administration of these medications to children receiving treatment for acute
      lymphoblastic leukemia (ALL) were systematically reviewed to determine the rate
      and types of medication errors occurring in these patients. METHODS: During a 2
      month study period, parents of children with ALL were contacted and asked to
      participate in the study before a regularly scheduled clinic appointment. At the
      visit, the parent demonstrated how each medication was administered. A pediatric
      oncologist reviewed the medical record to determine the correct treatment regimen
      for study patients. After comparing the correct treatment regimen with what was
      administered, a classification of "no medication error," "medication error," or
      "cannot determine" due to insufficient information was made for each indicated
      drug. Identified medication errors were subclassified as prescribing, dispensing,
      or administration errors. RESULTS: Data on 172 chemotherapeutic medications for
      69 patients were analyzed. One or more errors occurred with 17 of the 172 (9.9%)
      medications; a classification of "cannot determine" was made for 12 (7.0%)
      medications. Among the 17 medication errors there were 12 (7.0%) administration
      errors and 5 (2.9%) prescribing errors. There were no pharmacy dispensing errors.
      All errors were due to incorrect dosing or failure to administer an indicated
      medication. At least 1 medication error occurred in 13 of the 69 (18.8%) study
      patients. CONCLUSIONS: Prescribing and administration medication errors occurred
      with nearly 10% of chemotherapeutic drugs administered to outpatient children
      with ALL. Systematic changes, including computerized physician order entry and
      simplification of treatment protocols, should be considered.

PMID- 16909416
TI  - Criteria for downhill protein folding: calorimetry, chevron plot, kinetic
      relaxation, and single-molecule radius of gyration in chain models with subdued
      degrees of cooperativity.
AB  - Recent investigations of possible downhill folding of small proteins such as BBL
      have focused on the thermodynamics of non-two-state, "barrierless"
      folding/denaturation transitions. Downhill folding is noncooperative and
      thermodynamically "one-state," a phenomenon underpinned by a unimodal
      conformational distribution over chain properties such as enthalpy, hydrophobic
      exposure, and conformational dimension. In contrast, corresponding distributions
      for cooperative two-state folding are bimodal with well-separated population
      peaks. Using simplified atomic modeling of a three-helix bundle-in a scheme that
      accounts for hydrophobic interactions and hydrogen bonding-and coarse-grained
      C(alpha) models of four real proteins with various degrees of cooperativity, we
      evaluate the effectiveness of several observables at defining the underlying
      distribution. Bimodal distributions generally lead to sharper transitions, with a
      higher heat capacity peak at the transition midpoint, compared with unimodal
      distributions. However, the observation of a sigmoidal transition is not a
      reliable criterion for two-state behavior, and the heat capacity baselines, used
      to determine the van't Hoff and calorimetric enthalpies of the transition, can
      introduce ambiguity. Interestingly we find that, if the distribution of the
      single-molecule radius of gyration were available, it would permit discrimination
      between unimodal and bimodal underlying distributions. We investigate kinetic
      implications of thermodynamic noncooperativity using Langevin dynamics. Despite
      substantial chevron rollovers, the relaxation of the models considered is
      essentially single-exponential over an extended range of native stabilities.
      Consistent with experiments, significant deviations from single-exponential
      behavior occur only under strongly folding conditions.

PMID- 16909417
TI  - Detection of a hidden folding intermediate in the focal adhesion target domain:
      Implications for its function and folding.
AB  - The focal adhesion target (FAT) domain of focal adhesion kinase has a four-helix
      bundle structure. Based on a hydrogen exchange-constrained computer simulation
      study and some indirect experimental results, it has been suggested that a
      partially unfolded state of the FAT domain with the N-terminal helix unfolded
      plays an important role in its biological function. Here, using a native-state
      hydrogen exchange method, we directly detected an intermediate with the N
      terminal helix unfolded in a mutant (Y925E) of the FAT domain. In addition,
      kinetic folding studies on the FAT domain suggest that this intermediate exists
      on the native side of the rate-limiting transition state for folding. These
      results provide more direct evidence of the existence of the proposed
      intermediate and help to understand the folding mechanism of small single domain
      proteins.

PMID- 16909418
TI  - Crystal structure of 5'-methylthioadenosine nucleosidase from Arabidopsis
      thaliana at 1.5-A resolution.

PMID- 16909419
TI  - Unambiguous prediction of human integrin transmembrane heterodimer interactions
      using only homologous sequences.
AB  - Part of the interaction between the alpha- and beta-subunits of integrins is
      known to take place at the transmembrane (TM) domain, where both heteromeric and
      homomeric aggregates have been reported in vivo and in vitro. In a recent
      computational study, totally independent from biochemical or biophysical data, we
      explored the plausibility of various TM homo-oligomers using evolutionary
      conservation data as a filter for non-native interactions. We showed that several
      homodimeric and homotrimeric interactions for alpha- and beta-chains are
      evolutionarily conserved. We report herein the results of the application of the
      same exhaustive approach to the integrin heterodimer. We have studied all known
      human TM integrin alphabeta pairs, and we show unambiguously that two models of
      interaction are evolutionarily conserved. These two models are consistent with
      those proposed previously based on mutagenesis and crosslinking. Comparison with
      previous experimental data strongly supports that a glycophorin A-like model is
      an intermediate form of interaction between the resting state and the active
      form, where chain separation occurs. Surprisingly, these two models are also
      conserved when considering most of the possible alphabeta pair combinations,
      suggesting that specific pairing of integrins is not determined by the TM domain,
      which has remained unchanged in spite of the variety of known integrin functions.
      This fact highlights a common ancestral mechanism for signal transduction that
      has remained through evolution. In a broader context, our results show that it is
      possible to obtain correct and detailed interactions of alpha-helical
      heterodimers with total independence of experimental data.

PMID- 16909420
TI  - High resolution crystal structure of deoxy hemoglobin from Trematomus bernacchii
      at different pH values: the role of histidine residues in modulating the strength
      of the root effect.
AB  - The Root effect is a widespread property in fish hemoglobins (Hbs) that produces
      a drastic reduction of cooperativity and oxygen-binding ability at acidic pH.
      Here, we report the high-resolution structure of the deoxy form of Hb isolated
      from the Antarctic fish Trematomus bernacchii (HbTb) crystallized at pH 6.2 and
      8.4. The structure at acidic pH has been previously determined at a moderate
      resolution (Ito et al., J Mol Biol 1995;250:648-658). Our results provide a clear
      picture of the events occurring upon the pH increase from 6.2 to 8.4, observed
      within a practically unchanged crystal environment. In particular, at pH 8.4, the
      interaspartic hydrogen bond at the alpha(1)beta(2) interface is partially broken,
      suggesting a pK(a) close to 8.4 for Asp95alpha. In addition, a detailed survey of
      the histidine modifications, caused by the change in pH, also indicates that at
      least three hot regions of the molecule are modified (Ebeta helix, Cbeta-tail,
      CDalpha corner) and can be considered to be involved at various levels in the
      release of the Root protons. Most importantly, at the CDalpha corner, the break
      of the salt bridge Asp48alpha-His55alpha allows us to describe a detailed
      mechanism that transmits the modification from the CDalpha corner far to the
      alpha heme. More generally, the results shed light on the role played by the
      histidine residues in modulating the strength of the Root effect and also support
      the emerging idea that the structural determinants, at least for a part of the
      Root effect, are specific of each Hb endowed with this property.

PMID- 16909421
TI  - Conformational flexibility of RecA protein filament: transitions between
      compressed and stretched states.
AB  - RecA protein is a central enzyme in homologous DNA recombination, repair and
      other forms of DNA metabolism in bacteria. It functions as a flexible helix
      shaped filament bound on stretched single-stranded or double-stranded DNA in the
      presence of ATP. In this work, we present an atomic level model for
      conformational transitions of the RecA filament. The model describes small
      movements of the RecA N-terminal domain due to coordinated rotation of main chain
      dihedral angles of two amino acid residues (Psi/Lys23 and Phi/Gly24), while
      maintaining unchanged the RecA intersubunit interface. The model is able to
      reproduce a wide range of observed helix pitches in transitions between
      compressed and stretched conformations of the RecA filament. Predictions of the
      model are in agreement with Small Angle Neutron Scattering (SANS) measurements of
      the filament helix pitch in RecA::ADP-AlF(4) complex at various salt
      concentrations.

PMID- 16909422
TI  - Crystal structure of glycerophosphodiester phosphodiesterase from Agrobacterium
      tumefaciens by SAD with a large asymmetric unit.

PMID- 16909423
TI  - Clinical implications of the mechanism of epidermal growth factor receptor
      inhibitors.
AB  - Novel therapeutic agents that target the epidermal growth factor receptor (EGFR)
      constitute an important addition to the therapeutic armamentarium for the
      treatment of metastatic disease. EGFR-targeted agents currently approved by the
      U.S. Food and Drug Administration include cetuximab, a monoclonal antibody for
      the treatment of colorectal cancer; and the small-molecule EGFR tyrosine kinase
      inhibitor (TKI) erlotinib for the treatment of nonsmall cell lung cancer (NSCLC)
      and pancreatic cancer. Approval of the TKI gefitinib for NSCLC recently was
      withdrawn. Although both classes of anti-EGFR agents target the same receptor,
      substantial distinctions regarding their mechanism significantly affect dosing
      requirements, toxicity profiles, and their use as combination agents.

PMID- 16909424
TI  - Racial differences in doctors' information-giving and patients' participation.
AB  - BACKGROUND: Whether doctor-patient communication differs by race was investigated
      in patients with pulmonary nodules or lung cancer. METHODS: Eligible patients (n
      = 137) had pulmonary nodules or lung cancer and were seen in thoracic surgery or
      oncology clinics for initial treatment recommendations at a large southern
      Veterans Affairs Medical Center from 2001-2004. Doctor-patient consultations were
      audiotaped. Audiotapes were transcribed, unitized into utterances, and utterances
      were coded as doctors' information-giving or patients' and companions' active
      participation (asking questions, expressing concerns, and making assertions).
      Data were compared by patient race and doctor-patient racial concordance using t
      tests or chi-square tests as appropriate. Mixed linear regression was used to
      determine the independent predictors of doctor's information-giving after
      controlling for clustering of patients by doctor. RESULTS: Patient age, gender,
      marital status, clinical site, and health status were similar by race (P > .20),
      but black patients were somewhat less likely to have education beyond high school
      and to bring a companion to the visit (P = .06) than white patients. Black
      patients and their companions received significantly less information from
      doctors (49.3 vs. 87.3 mean utterances; P < .001) and produced significantly
      fewer active participation utterances (21.4 vs. 37.2; P < .001) than white
      patients. In mixed regression analyses, after adjusting for patients' and
      companions' participation, clustering by doctor, and other factors, race no
      longer predicted information-giving (P = .54). Patients in racially discordant
      interactions received significantly less information and were significantly less
      active participants (P < .001) when compared with patients in racially concordant
      interactions, and after controlling for patients' participation and other factors
      using mixed regression, racial discordance did not predict information-giving.
      CONCLUSIONS: The results indicate a pattern of communication that may perpetuate
      patient passivity and limited information exchange where black patients and
      patients in discordant interactions do less to prompt doctors for information and
      doctors in turn provide less information to these patients.

PMID- 16909425
TI  - The risk of second primary tumors in patients with nasopharyngeal carcinoma after
      definitive radiotherapy.
AB  - BACKGROUND: Second primary tumors (SPTs) have a substantial impact on survival in
      cancer patients. However, risk factors for SPTs have not been documented well,
      especially in nasopharyngeal carcinoma (NPC). The objective of this retrospective
      analysis was to evaluate such risks in patients with NPC after they received
      definitive radiation treatment. METHODS: Three hundred twenty-six consecutive
      patients with pathologically confirmed, nonmetastatic, undifferentiated NPC who
      received treatment between January 1, 1994 and December 30, 1995 were analyzed.
      All patients were restaged in accordance with the 2002 American Joint Committee
      on Cancer staging classification. There were 18 patients (5.5%) with Stage I NPC,
      152 patients (46.6%) with Stage II NPC, 101 patients (31.0%) with Stage III NPC,
      and 55 patients (16.9%) with Stage IVA or IVB NPC at initial diagnosis. All
      patients received definitive radiotherapy with either Cobalt-60 or megavoltage
      therapy. High-dose-rate brachytherapy was given to 23 patients either as part of
      their primary treatment or as adjuvant treatment for residual lesions. RESULTS:
      The median follow-up for all patients was 5.6 years (range, 1.0-8.0 years).
      Seventeen patients (5.2%) developed SPTs, for an average annual rate of 1.0%, and
      the 5-year cumulative incidence was 5.8%. Six SPTs were located within the
      radiation field. The cumulative incidence of in-field SPTs was 0.35% at 3 years
      and 1.2% at 5 years, and the average annual rate was 0.35%. Eleven patients
      (64.7%) had tumors of the upper aerodigestive tract (UADT). Among the 14 SPTs
      that occurred within 5 years after radiotherapy, only 3 tumors (21.4%) occurred
      within the radiation field. In contrast, all 3 SPTs that occurred >5 years after
      radiotherapy occurred within the radiation field (P = .029). Multivariate
      analysis showed that age was the only independent risk factor for developing SPTs
      after RT for NPC. Advanced age (age >or=50 years) was associated with a 37%
      increased risk of developing SPTs (relative risk, 1.367; 95% confidence interval,
      1.067-1.1753; P = .014). Other factors, including gender, tumor or lymph node
      classification, chemotherapy, total radiation dose to the nasopharynx,
      reirradiation, and adjuvant brachytherapy did not influence the risk of SPTs.
      CONCLUSIONS: SPTs in patients with NPC occurred preferentially in the UADT and
      tended to develop within the irradiated field >5 years after patients received
      radiation. Older patients with NPC (age >or=50 years) may be at increased risk.
      Further studies with larger samples and longer follow-up will be needed to
      confirm these findings.

PMID- 16909427
TI  - Screening for psychological distress in Turkish cancer patients.
AB  - The distress thermometer (DT) is a useful measure of psychological distress in
      cancer patients. Our objective was to investigate distress impact on oncology
      patients in Turkey and determine the optimal cut-off score on the DT for
      identifying clinically significant distress. One hundred and eighty two cancer
      patients completed the DT, Problem List (PL), and Hospital Anxiety and Depression
      scale (HADS), The European Organization for Research and Treatment of Cancer
      Quality of Life Questionnaire (EORTC QLQ-C30 version 3.0). The receiver operating
      characteristic (ROC) curve analyses of DT scores yielded an estimated area under
      the curve of 0.66 when compared to the HADS cut-off score, suggesting the DT is
      an effective scale to discriminate between classified cancer patients both with
      and without clinically significant distress. The DT cut-off score of 4 yielded
      the optimal combination of sensitivity and specificity. Scores on the DT were
      moderately correlated to the HADS (p<0.01) and EORTC QLQ-C30. Based on the
      significant correlations, we conclude that the DT has acceptable criterion
      validity.

PMID- 16909426
TI  - A phase II study of gemcitabine and capecitabine in metastatic renal cancer: a
      report of Cancer and Leukemia Group B protocol 90008.
AB  - BACKGROUND: The objective of this study was to verify previous reports of
      activity with gemcitabine plus a fluoropyrimidine in patients with metastatic
      renal cell cancer in a multiinstitutional setting. METHODS: Eligibility included
      a Zubrod performance status from 0 to 2, no prior gemcitabine or fluoropyrimidine
      therapy, and normal organ function. Patients received gemcitabine at a dose of
      1000 mg/m2 on Days 1, 8, and 15 and capecitabine at a dose of 830 mg/m2 twice
      daily on Days 1 through 21 on a 28-day cycle with specified dose reductions for
      baseline renal insufficiency. The primary endpoint was the response rate, which
      was assessed every 8 weeks. The statistical plan tested the hypothesis that the
      response rate was 5% versus an alternative of 15%. RESULTS: Sixty patients were
      enrolled, and 4 of those patients never started treatment. Of the 56 evaluable
      patients, 79% of patients underwent prior nephrectomy, 75% of patients received
      prior systemic therapy, and 75% of patients had clear cell histology. Risk
      stratification revealed that 34%, 43%, and 16% of patients were in Risk Groups 1,
      2, and 3, respectively. Toxicity (graded according to the National Cancer
      Institute's Common Toxicity Criteria [version 2.0]) included Grade 3 or 4
      neutropenia in 45% of patients, Grade 2 or greater fatigue in 32% of patients,
      Grade 2 or greater nausea in 29% of patients, Grade 2 or greater hand-foot
      reaction in 39% of patients, and Grade 2 or greater diarrhea in 22% of patients.
      Six patients responded (11%; 95% confidence interval, 4-22%), and the overall
      median survival was 14.5 months. CONCLUSIONS: Gemcitabine plus capecitabine had
      modest activity in patients with metastatic renal cancer, although the degree of
      activity and its associated toxicity would not support further evaluation in a
      Phase III trial of unselected patients. More focused investigations to identify
      patients most likely to benefit or to enhance activity with additional agents
      would be reasonable.

PMID- 16909428
TI  - A prospective study of the impact of genetic susceptibility testing for BRCA1/2
      or HNPCC on family relationships.
AB  - This study assessed the impact of genetic testing for cancer susceptibility on
      family relationships and determinants of adverse consequences for family
      relationships. Applicants for genetic testing of a known familial pathogenic
      mutation in BRCA1/2 or a HNPCC related gene (N=271) rated the prevalence and
      nature of changes in family relationships, familial difficulties and conflicts
      due to genetic testing 6 months after receiving the test result. The level of
      family functioning, differentiation from parents, support and familial
      communication style regarding hereditary cancer were assessed before receiving
      the test result. Genetic testing affected some family relationships in a positive
      way (37%), i.e. by feeling closer, improved communication and support, more
      appreciation of the relative and relief of negative test result. A minority
      reported unwanted changes in relationships (19%), problematic situations (13%) or
      conflicts (4%). Adverse effects comprised feelings of guilt towards children and
      carrier siblings, imposed secrecy and communication problems. Predictors of
      adverse consequences on family relationships were reluctance to communicate about
      hereditary cancer with relatives and disengaged-rigid or enmeshed-chaotic family
      functioning. Open communication between relatives should be stimulated because a
      lack of open communication may be an important determinant of familial adverse
      effects.

PMID- 16909429
TI  - Respiratory peripheral chemosensory irritation, acute and repeated exposure
      toxicity studies with aerosols of triethylene glycol.
AB  - The potential for adverse effects from exposure to respirable aerosols of
      triethylene glycol (TEG: CAS Number 112-27-6) was investigated by a peripheral
      chemosensory irritation study, and by acute and repeated exposure toxicity
      studies. The sensory irritation study, conducted with male Swiss Webster mice,
      showed an exposure concentration-related depression of breathing rate that
      allowed the calculation of an RD50 of 5140 mg m(-3). In an acute study male and
      female Sprague Dawley rats were exposed whole body to aerosols of TEG up to 6730
      mg m(-3) for 4 h. No mortalities occurred at this high concentration, but
      unexplained mortality occurred in female rats at 5230 mg m(-3) at 2-3 days
      postexposure. Two repeats of the 5230 mg m(-3) exposure did not cause mortality.
      Signs at 6730 and 5230 mg m(-3) were limited to those of irritancy. For a 9 day
      repeated exposure study rats were exposed whole body to 0, 494, 2011 and 4824 mg
      m(-3) TEG aerosols for 6 h day(-1). Mortalities occurred at 4824 mg m(-3) between
      exposure days 2 and 5. Nonspecific indications of toxicity at 2011 mg m(-3) were
      signs of irritation, decreased body weight and increased food and water
      consumption; evidence of hepatic dysfunction was indicated by increased serum
      alkaline phosphatase and alanine aminotransferase activities, but liver histology
      was normal. Fluid imbalance was suggested by increases in water consumption,
      blood urea nitrogen, relative kidney weight and urine volume, with decreased
      urine osmolality, pH and N-acetyl-beta-D-glucosaminidase activity. At 494 mg m(
      3) there were minimal signs of irritation, increased water consumption and
      slightly increased alkaline phosphatase; histology of the kidney was normal.
      Thus, in this 9 day repeated aerosol whole body exposure study a No-Observed
      Effect-Level (NOEL) could not be established. Since preening of the fur at these
      high aerosol concentrations exposures might have led to a confounding factor from
      the resultant oral intake, another 9 day repeated aerosol study was conducted,
      but by nose-only exposure of rats for 6 h day(-1) to TEG aerosol concentrations
      of 0, 102, 517 and 1036 mg m(-3). In this study there were no clinical signs, no
      effects on food and water consumption, and no biochemical or histological
      evidence of hepatorenal dysfunction. By the end of the exposure period, male and
      female rats of the 1036 mg m(-3) group had body weights lower than those of the
      controls, but not with statistical significance. Since there were no
      statistically significant effects on any monitors, 1036 mg m(-3) is considered to
      be a threshold for toxicity by nose-only exposure to TEG aerosol. The findings
      indicate that exposure to a respirable aerosol is not acutely harmful, but may
      cause sensory irritant effects. Repeated exposure to high concentrations of TEG
      aerosols may be harmful, particularly if there are contributions from additional
      routes of exposure.

PMID- 16909430
TI  - Cyclophilin A is required for M-CSF-dependent macrophage proliferation.
AB  - The immunosuppressor sanglifehrin A (SfA) is a member of a family of immunophilin
      cyclophilin A-binding molecules and does not inhibit calcineurin activity.
      Sanglifehrin A inhibits M-CSF-dependent macrophage proliferation by arresting the
      G1 phase of the cell cycle but does not affect cell viability. This
      immunosuppressor exerts its action on proliferation by inactivating cyclin
      dependent kinase 2 (Cdk2) activity. Moreover, c-myc expression is also repressed.
      In the early steps of M-CSF signaling, SfA inhibits the phosphorylation of Raf-1
      and the external regulated kinases (ERK)1/2 and mitogen-activated protein kinase
      phosphatase-1, which are required for proliferation. The effects of SfA are not
      related to a block of the proteosome activity. These data show that immunophilin
      contributes to M-CSF-dependent proliferation through activation of the Raf
      1/MEK/ERK pathway and the regulation of Cdk activities, which is required for
      cell cycle progression.

PMID- 16909432
TI  - In vivo magnetic resonance imaging of dendritic cell migration into the draining
      lymph nodes of mice.
AB  - Dendritic cell (DC) migration into the draining lymph nodes is critical for T
      cell priming. Here, we show that magnetic resonance imaging (MRI) can be used to
      visualize DC migration in vivo. We combined clinically approved small particles
      of iron oxide (SPIO) with protamine sulfate to achieve efficient uptake by murine
      bone marrow-derived DC. SPIO-DC were largely unaltered and after injection into
      the footpads of mice, they migrated into the T cell areas of the draining lymph
      nodes, which could be visualized by MRI. Distinct MRI signal reduction patterns
      correlated with the detection of SPIO-DC mainly within Thy-1.2+ B220- T cell
      areas, as confirmed by iron staining and immunohistology. Clear signal reduction
      patterns could still be observed with 1x10(6) injected SPIO-DC at high
      resolution, resulting in the detection of about 2000 DC. Control injections of
      homing-incompetent SPIO-DC derived from CCR7-/- mice or SPIO alone did not reach
      the T cell areas. Taken together, the results demonstrate that clinically
      approved contrast agents allow the non-invasive visualization of DC migration
      into the draining lymph node by MRI in vivo at high resolution. This protocol
      therefore also allows dynamic imaging of immune responses and MRI-based tracking
      of human DC in patients.

PMID- 16909431
TI  - TCR-independent cytokine stimulation induces non-MHC-restricted T cell activity
      and is negatively regulated by HLA class I.
AB  - Recent evidence suggests that the functional status of T cells activated
      independently from their TCR differs substantially from classical MHC-restricted
      T cells. Here, we show that TCR-independent, short-term stimulation via the
      common gamma-chain of the IL-2/IL-15 receptor induces non-MHC-restricted
      cytotoxicity and sustained cytokine secretion in purified CD4+ or CD8+ T cells.
      NK-like cytotoxicity is directed against MHC class I-negative targets and can be
      inhibited by classical and non-classical HLA class I molecules. Known inhibitory
      receptors, such as CD85j (ILT2) and leukocyte-associated Ig-like receptor-1, are
      not responsible for this HLA-mediated inhibition. NK-like cytotoxicity can be
      costimulated by NKG2D (CD314) triggering, but 2B4 (CD244) and DNAM-1 (CD226) are
      not involved. NK-like T cells display an activated phenotype and secrete various
      cytokines, including IFN-gamma, TNF-alpha, IL-5, IL-13 and MIP-1beta. Under
      normal conditions, HLA class I-mediated inhibition may function as a safety
      mechanism to prevent unbalanced cytokine production and effector killing
      mechanisms by T cells that were activated independently from their TCR. Non-MHC
      restricted activity represents a functional status rather than a property of
      distinct T cell subpopulations. Thus, cytokine-induced, non-MHC-restricted T
      cells may be relevant in immune responses against tumors showing aberrant MHC
      expression through their capacities of cytokine production and direct tumor cell
      eradication.

PMID- 16909433
TI  - Induction of IgE and allergic-type responses in fur mite-infested mice.
AB  - High serum IgE levels are characteristic of allergic diseases and immune
      responses to nematode parasites. A murine allergy model based on infestation with
      the fur mites Myocoptes musculinus and Myobia musculi was investigated. Analysis
      of mite infestation in various knockout mice revealed that IgE production in
      response to these ectoparasites was dependent on T cells, IL-4, and CD40L.
      Secretion of IL-4 by CD4+ T cells obtained from peripheral LN draining mite
      infested skin sites was increased with progressing mite infestation and
      correlated with the serum IgE induction. A time course analysis of the mRNA
      expression of switched IgE, activation-induced cytidine deaminase (AID), and
      epsilon germ-line transcripts (epsilonGLT) suggested that switching to IgE in
      response to fur mites occurred initially in skin-draining LN. In addition, mite
      infestation induced mast cell degranulation in the skin as well as mast cell
      infiltration into skin-draining LN. Analysis of the immune response generated in
      mite-infested mice is a valuable model for the investigation of allergic
      disorders and provides information for better understanding of mechanisms
      involved in IgE induction and regulation in a physiological way of allergen
      exposure resembling atopic sensitization in humans.

PMID- 16909434
TI  - Interaction between the CCR5 chemokine receptors and microbial HSP70.
AB  - Evidence is presented that the microbial 70-kD heat shock protein (HSP70) binds
      to CCR5 chemokine receptors in CCR5-transfected cell lines and in primary human
      cells. Significant CCR5-mediated calcium mobilization was stimulated by HSP70 and
      inhibited with TAK 779, which is a specific CCR5 antagonist. HSP70-mediated
      activation of the p38 MAPK phosphorylation signaling pathway was also
      demonstrated in CCR5-transfected HEK 293 cells. Direct binding of three
      extracellular peptides of CCR5 to HSP70 was demonstrated by surface plasmon
      resonance. Functional evidence of an interaction between HSP70, CCR5 and CD40 was
      shown by enhanced production of CCL5 by HEK 293 cells transfected with both CD40
      and CCR5. Primary monocyte-derived immature DC stimulated with HSP70 produced IL
      12 p40, which showed dose-dependent inhibition of >90% on treatment with both TAK
      779 and anti-CD40 mAb. Stimulation of IL-12 p40 or TNF-alpha by HSP70 was related
      to the differential cell surface expression of CCR5 in primary human immature and
      mature DC, and those with the homozygous triangle DeltaDelta32 CCR5 mutation.
      These findings may be of significance in the interaction between HSP70 and immune
      responses of CCR5+ T cells in HIV-1 infection, as well as in inflammatory bowel
      disease.

PMID- 16909435
TI  - Activated NKT cells increase dendritic cell migration and enhance CD8+ T cell
      responses in the skin.
AB  - Activated NKT cells produce cytokines such as IL-4 and IFN-gamma that function
      locally to influence the strength and functional development of antigen-specific
      T cells. Here we identify an alternative mechanism by which NKT cells influence
      the strength of T cell responses: through modulation of peripheral dendritic cell
      (DC) trafficking. NKT cell activation with alpha-galactosylceramide induced high
      systemic levels of TNF-alpha that mediated increased DC migration from skin to
      draining lymph nodes. This increased DC trafficking led to a threefold increase
      in effector T cell priming and in the immune response elicited to antigen
      challenge when alpha-galactosylceramide was given at the time of immunization of
      the skin. These studies provide important implications for the use of NKT cell
      activation strategies to manipulate T cell-mediated responses including responses
      to cutaneous tumors and graft vs. host disease.

PMID- 16909437
TI  - Xyloccensin X and Y, two new limonoids from xylocarpus molluccensis: NMR
      investigation in mixture.
AB  - Two new limonoids, xyloccensin X (1) and xyloccensin Y (2), have been identified
      in mixture using NMR spectroscopy. Both limonoids were isolated in mixture from
      the fruit of the plant Xylocarpus molluccensis. The structures of these were
      proposed after extensive 2D NMR analyses in mixture.

PMID- 16909438
TI  - Real-time elastography--an advanced method of ultrasound: First results in 108
      patients with breast lesions.
AB  - OBJECTIVES: To evaluate whether real-time elastography, a new, non-invasive
      method for the diagnosis of breast cancer, improves the differentiation and
      characterization of benign and malignant breast lesions. METHODS: Real-time
      elastography was carried out in 108 potential breast tumor patients with
      cytologically or histologically confirmed focal breast lesions (59 benign, 49
      malignant; median age, 53.9 years; range, 16-84 years). Tumor and healthy tissue
      were differentiated by measurement of elasticity based on the correlation between
      tissue properties and elasticity modulus. Evaluation was performed using the
      three-dimensional (3D) finite element method, in which the information is color
      coded and superimposed on the B-mode ultrasound image. A second observer
      evaluated the elastography images, in order to improve the objectivity of the
      method. The results of B-mode scan and elastography were compared with those of
      histology and previous sonographic findings. Sensitivities and specificities were
      calculated, taking histology as the gold standard. RESULTS: B-mode ultrasound had
      a sensitivity of 91.8% and a specificity of 78%, compared with sensitivities of
      77.6% and 79.6% and specificities of 91.5% and 84.7%, respectively, for the two
      observers evaluating elastography. Agreement between B-mode ultrasound and
      elastography was good, yielding a weighted kappa of 0.67. CONCLUSIONS: Our
      initial clinical results suggest that real-time elastography improves the
      specificity of breast lesion diagnosis and is a promising new approach for the
      diagnosis of breast cancer. Elastography provides additional information for
      differentiating malignant BI-RADS (breast imaging reporting and data system)
      category IV lesions.

PMID- 16909439
TI  - In vitro immunomodulatory activities of a newly concocted traditional Chinese
      medicine formula: VI-28.
AB  - Previous studies have suggested that Vigconic VI-28, an anti-aging traditional
      Chinese medicine (TCM) formula containing Radix Ginseng and Cornu Cervi
      Pantotrichum, possesses immunological efficacy. This in vitro study further
      investigated the immunomodulatory effects of the hot water extracts of VI-28. The
      study included (1) colorimetric 5-bromo-2'-deoxy-uridine proliferation ELISA for
      estimating mitogenicity in human peripheral blood mononuclear cells (PBMC), (2)
      immunofluorescence staining for measuring the expression of IL-2 receptor alpha
      (CD25) on lymphocytes, (3) cytometric bead array (CBA) for quantifying cytokine
      liberation from PBMC, and (4) intracellular immunophenotyping for macrophage
      phagocytosis and hydrogen peroxide (H(2)O(2)) production from monocytes. The
      results demonstrated that VI-28 (1) could dose-dependently inhibited the
      proliferation of unstimulated and lipopolysaccharide-activated PBMC but enhanced
      the proliferation of phytohemagglutinin-activated PBMC at concentrations of <1
      mg/mL, (2) significantly augmented the expression of CD25 on lymphocytes at
      concentrations of 0.4 mg/mL or above (p < 0.05), (3) dose dependently (0.1-1.0
      mg/mL) activated macrophage phagocytosis and monocyte synthesis of H(2)O(2) and
      (4) significantly increased the production of cytokines IL-8, IL-10, IL-12 and IL
      1beta at various concentrations of VI-28 (p < 0.05). The results suggest that VI
      28 is a potential immunomodulator which probably acts through the activation of
      lymphocytes and monocytes.

PMID- 16909440
TI  - Preventive effects of Azadirachta indica on benzo(a)pyrene-DNA adduct formation
      in murine forestomach and hepatic tissues.
AB  - In the present investigation, the effects of aqueous Azadirachta indica leaf
      extract (AAILE) on (3)H-benzo(a)pyrene-DNA [(3)H-B(a)P-DNA] adduct formation, the
      status of biotransformation enzymes and reduced glutathione (GSH) content were
      evaluated in the forestomach and liver of Balb/c mice. Two weeks of AAILE
      treatment reduced the (3)H-B(a)P-DNA adduct levels by 31.6% in forestomach
      tissue. Similarly, (3)H-B(a)P-DNA adduct levels were decreased by 34.7% in the
      liver of AAILE treated mice compared with their control counterparts. After AAILE
      treatment, the cytochrome P450 content decreased, whereas the GSH content
      increased significantly in the hepatic tissue. In the forestomach as well as in
      the liver, the cytochrome b5 content declined, whereas an increase in glutathione
      S-transferase (GST) activity was observed in both tissues. These observations
      suggested that AAILE may have reduced the metabolic activation of (3)H-B(a)P with
      enhanced detoxification of its active metabolites, hence the observed decrease in
      the levels of (3)H-B(a)P-DNA adducts. These molecular and biochemical modulations
      observed at the initiation phase of carcinogenesis seems to be significant and
      could be correlated with the chemopreventive effects of A. indica against B(a)P
      induced forestomach tumorigenesis.

PMID- 16909441
TI  - Potential medicinal plants for CNS disorders: an overview.
AB  - Although very few drugs are currently approved by regulatory authorities for
      treating multi-factorial ailments and disorders of cognition such as Alzheimer's
      disease, certain plant-derived agents, including, for example, galantamine and
      rivastigmine (a semi-synthetic derivative of physostigmine) are finding an
      application in modern medicine. However, in Ayurveda, the Indian traditional
      system of medicine which is more than 5000 years old, selected plants have long
      been classified as 'medhya rasayanas', from the Sanskrit words 'medhya', meaning
      intellect or cognition, and 'rasayana', meaning 'rejuvenation'. These plants are
      used both in herbal and conventional medicine and offer benefits that
      pharmaceutical drugs lack. In the present article, an attempt has been made to
      review the most important medicinal plants, including Ginkgo biloba, St John's
      wort, Kava-kava, Valerian, Bacopa monniera and Convolvulus pluricaulis, which are
      widely used for their reputed effectiveness in CNS disorders.

PMID- 16909443
TI  - NF-kappaB modulators from Valeriana officinalis.
AB  - Valeriana officinalis (Valerianaceae) has been of great interest for its
      therapeutic uses for treating mild nervous tension and temporary sleeping
      problems. In traditional European medicine it has been also reported as an
      antiinflammatory remedy. This study reports that the EtOAc extract of the
      underground parts of V. officinalis showed inhibitory activity against NF-kappaB
      at 100 microg/mL in the IL-6/Luc assay on HeLa cells and provided protection
      against excitotoxicity in primary brain cell cultures at micromolar
      concentrations. Bioassay-guided fractionation of the EtOAc extract led to the
      isolation of three known sesquiterpenes: acetylvalerenolic acid (1), valerenal
      (2) and valerenic acid (3), 1 and 3 were active as inhibitors of NF-kappaB at a
      concentration of 100 microg/mL. Acetylvalerenolic acid (1) reduced NF-kappaB
      activity to 4%, whereas valerenic acid (3) reduced NF-kappaB activity to 25%.

PMID- 16909442
TI  - Evaluation of nitric oxide scavenging activity, in vitro and ex vivo, of selected
      medicinal plants traditionally used in inflammatory diseases.
AB  - Steroidal and non-steroidal antiinflammatory drugs, despite their various side
      effects, are in great demand worldwide. Alternatively, herbal formulations
      provide relief to a large percentage of the population suffering from
      inflammatory diseases. Therefore, such practices need to be rationalized through
      a mechanistic approach. Thus, four traditional medicinal plants, namely Ventilago
      madraspatana Gaertn., Rubia cordifolia Linn., Lantana camara Linn. and Morinda
      citrifolia Linn. were selected for a study on the inhibition of nitric oxide
      (NO*), a key mediator in the phenomenon of inflammation, signifying the presence
      of effective antiinflammatory constituents therein. Plant samples were extracted
      with different solvents for evaluation of their inhibitory activity on NO*
      produced in vitro from sodium nitroprusside, and in LPS-activated murine
      peritoneal macrophages, ex vivo. Further, the inhibition of NO* synthesis was
      correlated with the reduction of iNOS protein expression through Western blot.
      Notable NO* scavenging activity was exhibited in vitro by some extracts of V.
      madraspatana, R. cordifolia and L. camara (IC(50) < 0.2 mg/mL). Most of them
      showed marked inhibition (60%-80%), ex vivo, at a dose of 80 microg/mL without
      appreciable cytotoxic effect on the cultured macrophages. Immunoblot analysis
      confirmed that the modulatory effect of the samples had occurred through
      suppression of iNOS protein.

PMID- 16909444
TI  - Neuropharmacological evaluation of Ginkgo biloba phytosomes in rodents.
AB  - On oral administration, Ginkgo biloba phytosomes significantly reduced
      pentobarbitone-induced sleeping time, produced an alteration in the general
      behaviour pattern, increased spontaneous motility and inhibited the
      chlorpromazine-induced blockade of conditioned and unconditioned responses in
      rodents. They exhibited both antiamnestic and antidepressant activities in the
      scopolamine-induced amnesia test and behavioural despair test, respectively.
      However, the phytosomes failed to show anticonvulsant activity. The observations
      suggest that the G. biloba phytosomes possess moderate antiamnestic/nootropic
      activity.

PMID- 16909446
TI  - Evaluation of antioxidant activity of Ginkgo biloba phytosomes in rat brain.
AB  - Ginkgo biloba from the traditional Chinese system of medicine has been found to
      possess neurocognitive enhancing effects. The mechanism of action of Ginkgo seems
      to be related to its antioxidant properties. In the present study, Ginkgo biloba
      phytosomes were administered to Wistar rats at 50 mg/kg and 100 mg/kg for 7 and
      14 days. Chemical hypoxia was induced by administration of sodium nitrite (75
      mg/kg) 1 h after the last administration of treatment. Thirty minutes after
      sodium nitrite administration, the animals were killed and the cerebral cortex,
      cerebellum, hippocampus and striatum were isolated and homogenized. The
      supernatants were used for the estimation of the antioxidant enzymes superoxide
      dismutase, catalase, glutathione peroxidase and glutathione reductase. Ginkgo
      biloba phytosome treatment was found to increase superoxide dismutase, catalase,
      glutathione peroxidase and glutathione reductase activities in all the brain
      regions compared with those treated only with sodium nitrite. The prevention of
      depletion of the antioxidant enzymes by sodium nitrite in the presence of Ginkgo
      biloba phytosomes may be correlated to its antioxidant activity.

PMID- 16909448
TI  - Foul weather ahead and we're low on gas.

PMID- 16909447
TI  - Antioxidative effects of pumpkin seed (Cucurbita pepo) protein isolate in CCl4
      induced liver injury in low-protein fed rats.
AB  - The effects of pumpkin seed (Cucurbita pepo) protein isolate on the plasma
      activity levels of catalase (CA), superoxide dismutase (SOD), glutathione
      peroxidase (GSHpx) and total antioxidant capacity (TAC) as well as glucose-6
      phosphatase (G6Pase) in liver homogenates and lipid peroxidation (LPO
      malondialdehyde-MDA) levels in liver homogenates and liver microsomal fractions
      against carbon tetrachloride (CCl(4))-induced acute liver injury in low-protein
      fed Sprague-Dawley rats (Rattus norvegicus) were investigated. A group of male
      Sprague-Dawley rats maintained on a low-protein diet for 5 days were divided into
      three subgroups. Two subgroups were injected with carbon tetrachloride and the
      other group with an equivalent amount of olive oil. Two hours after CCl(4)
      intoxication one of the two subgroups was administered with pumpkin seed protein
      isolate and thereafter switched onto a 20% pumpkin seed protein isolate diet. The
      other two groups of rats were maintained on the low-protein diet for the duration
      of the investigation. Groups of rats from the different subgroups were killed at
      24, 48 and 72 h after their respective treatments. After 5 days on the low
      protein diet the activity levels of all the enzymes as well as antioxidant levels
      were significantly lower than their counterparts on a normal balanced diet.
      However, a low-protein diet resulted in significantly increased levels of lipid
      peroxidation. The CCl(4) intoxicated rats responded in a similar way, regarding
      all the variables investigated, to their counterparts on a low-protein diet. The
      administration of pumpkin seed protein isolate after CCl(4) intoxication resulted
      in significantly increased levels of all the variables investigated, with the
      exception of the lipid peroxidation levels which were significantly decreased.
      From the results of the present study it is concluded that pumpkin seed protein
      isolate administration was effective in alleviating the detrimental effects
      associated with protein malnutrition and CCl(4) intoxication. It is therefore
      apparent that pumpkin seed protein isolate has components that have
      antiperoxidative properties.

PMID- 16909445
TI  - In vitro evaluation of effects of two Ghanaian plants relevant to wound healing.
AB  - Commelina diffusa and Spathodea campanulata are used as wound-healing agents in
      Ashanti traditional medicine in Ghana. The methanol extracts of Commelina diffusa
      herb and Spathodea campanulata bark showed some level of antimicrobial activity
      with C. diffusa exhibiting selective antifungal activity against Trichophyton
      species. The extracts reduced the peroxidation of bovine brain extract with an
      IC(50) value of 1.39 mg/mL and 0.24 mg/mL, respectively. In addition the extracts
      also exhibited significant antioxidant activity by protecting MRC-5 cells from
      hydrogen peroxide induced oxidant injury at concentrations between 1 microg/mL
      and 10 microg/mL. The extracts showed no inhibition of NF-kappaB at 100
      microg/mL. The antioxidant activities and antimicrobial activities suggest that
      the use of the plants in wound healing may be based on antioxidant and antiseptic
      effects of its constituents.

PMID- 16909449
TI  - Health effects of human population isolation and admixture.

PMID- 16909450
TI  - Strategy for mapping quantitative trait loci (QTL) by using human
      metapopulations.
AB  - AIM: To present a novel strategy for mapping quantitative trait loci (QTL), using
      human metapopulations. The strategy is based on the expectation that in
      geographic clusters of small and distinct human isolates, a combination of
      founder effect and genetic drift can dramatically increase population frequency
      of rare QTL variants with large effect. In such cases, the distribution of QT
      measurements in an (affected) isolate is expected to deviate from that observed
      in neighboring isolates. METHODS: We tested this hypothesis in 9 villages from a
      larger Croatian isolate resource, where 7 Mendelian disorders have been
      previously reported. The values of 10 physiological and biochemical QTs were
      measured in a random sample of 1001 individuals (100 inhabitants of each of 9
      villages and 101 immigrant controls). RESULTS: Significant over- or under-
      representation of individuals from specific villages in extreme ends of
      standardized QT measurement distribution was found 10 times more frequently than
      expected by chance. The large majority of such clusters of individuals with
      extreme QT values (34/36, 94.4%) originated from the 6 villages with the most
      pronounced geographic isolation and endogamy. CONCLUSION: Early epidemiological
      assessment supports the feasibility of the proposed strategy. Clusters of
      individuals with extreme QT values responsible for over-representation of single
      villages can usually be linked to a larger pedigree and may be useful for further
      QTL mapping, using linkage analysis.

PMID- 16909453
TI  - High incidence of glucose-6-phosphate dehydrogenase deficiency in Croatian island
      isolate: example from Vis island, Croatia.
AB  - AIM: To determine the prevalence of glucose-6-phosphate dehydrogenase (G6PD)
      deficiency in the population of the town of Komiza on the island of Vis, which
      has previously been reported as a place with several cases of favism. METHODS: We
      screened 302 randomly selected men, using the fluorescent spot test. Fluorescence
      readings were performed at the beginning and 5, 10, and 20 minutes after
      incubation, and were classified into three groups: bright fluorescence, weak
      fluorescence, and no fluorescence. All men found to be G6PD deficient were tested
      with a quantitative spectrophotometric UV method. RESULTS: Of the 302 tested
      blood samples, 36 (11.9%) samples showed weak fluorescence or no fluorescence
      spots. Spectrophotometric UV test showed that 18 (5.96%) men were G6PD deficient.
      The prevalence of G6PD deficiency in the population of Komiza is significantly
      higher (P<0.001) than the prevalence in the whole population of Dalmatia in the
      south of Croatia (0.75% in men). CONCLUSION: On the basis of these findings, we
      recommend including the newborns from the island of Vis into a screening program
      for G6PD deficiency. Our results indicate that G6PD deficiency should be
      determined for all the island isolates in the Mediterranean basin and they
      warrant further studies.

PMID- 16909451
TI  - Mendelian diseases and conditions in Croatian island populations: historic
      records and new insights.
AB  - Among Croatian islands, there are several which are known for unusual
      autochthonous diseases and specific medical conditions that result from the
      reproductive isolation and specific population genetic structure. These
      populations are characterized by high degree of genetic isolation, consanguinity,
      and inbreeding. The reported diseases include Mal de Meleda on Mljet island,
      hereditary dwarfism on Krk island, familial learning disability on Susak island,
      familial ovarian cancer on Lastovo island, and several other rare diseases and
      conditions inherited in Mendelian fashion. We present a historical perspective on
      how these conditions were first described, interpreted, and assessed. We reviewed
      the information obtained through genetic research in the past several years, when
      the genetic etiology of some of these conditions was explained. The disease gene
      causing Mal de Meleda was first localized at 8q chromosome, and mutations in the
      ARS (component B) gene encoding SLURP-1 (secreted mammalian Ly-6/uPAR-related
      protein 1) protein were identified subsequently. The genetic etiology of dwarfism
      on the island of Krk is explained by a mutation in the PROP1 gene, responsible
      for the short stature. The search for mutations underlying other monogenic
      diseases in Croatian islands is under way.

PMID- 16909452
TI  - Lifestyle, genetics, and disease in Sami.
AB  - AIM: To present a summary of the lifestyle, genetic origin, diet, and disease in
      the population of Sami, indigenous people of northern Fennoscandia. METHOD: A
      survey of the available scientific literature and preliminary results from our
      own study of the Swedish Sami population. RESULTS: The Sami probably have a
      heterogeneous genetic origin, with a major contribution of continental or Eastern
      European tribes and a smaller contribution from Asia. The traditional Sami diet,
      high in animal products, persists in Sami groups still involved with reindeer
      herding, but others have adopted a diet typical of Western cultures. Early
      reports indicated a lower prevalence of heart disease and most cancers, except
      stomach cancer. Recent studies have not found a lower risk of heart disease, but
      have consistently shown an overall reduced cancer risk. Sami have been reported
      to share some specific health-related genetic polymorphisms with other European
      populations, but none that would explain the observed differences in disease
      risk. CONCLUSION: The genetic structure of the Sami population makes it suitable
      for studies of the genetic and environmental factors influencing the development
      of common diseases. The difference in incidence of heart disease between studies
      may reflect the ongoing transition from a traditional to a more Westernized
      lifestyle. The ability to compare population segments with different lifestyles,
      combined with the genetic structure of the population, creates unusual
      possibilities for studies of the genetic and environmental factors involved in
      the development of common disease.

PMID- 16909454
TI  - NeuroD1 gene and interleukin-18 gene polymorphisms in type 1 diabetes in
      Dalmatian population of Southern Croatia.
AB  - AIM: To evaluate the frequency of known polymorphisms in the exon 2 of the
      NeuroD1 gene and in the interleukin (IL)-18 promoter region in patients with type
      1 diabetes mellitus (T1DM) and in healthy control subjects in Dalmatia, Southern
      Croatia. METHODS: A total of 134 unrelated patients (73 men and 61 women) and 132
      consecutive unrelated healthy controls (61 men and 71 women) from the Dalmatian
      region of southern Croatia were recruited for the study. NeuroD1 genotypes (GG,
      GA, AA) were identified by means of polymerase chain reaction followed by
      restriction fragment length polymorphism (PCR/RFLP). IL-18 polymorphism in the
      position -137 of the promoter region was detected by using PCR sequence-specific
      primers. RESULTS: Genotype distributions of both genes did not show significant
      difference between patients and controls. CONCLUSION: Our results suggest that
      NeuroD1 exon 2 and IL-18 promoter gene polymorphisms are not associated with
      development of T1DM susceptibility in the population of South Croatia. In
      addition to previously published positive correlations of these polymorphisms
      with development of T1DM among different world populations, our findings indicate
      the existence of ethnic variations in the association of these genes with disease
      development.

PMID- 16909455
TI  - Historic exposure to plague and present-day frequency of CCR5del32 in two
      isolated island communities of Dalmatia, Croatia.
AB  - AIM: To assess the frequency of deletion of 32 base pairs in a CCR5 gene, shown
      to confer resistance to HIV infection, in two isolated island communities of
      Dalmatia, Croatia, with different histories of exposure to (plague) during the
      medieval period and beyond. METHODS: Random samples of 100 individuals from
      highly isolated communities of Lopar (island of Rab) and Komiza (island of Vis)
      were selected in 2002 and their DNA was extracted. An extremely high level of 3
      generational endogamy was found in both communities (98% and 91%, respectively),
      indicating very limited gene flow, which was confirmed by available historic
      records. The two settlements also differed in their historic exposure to plague:
      between 1449 and 1456, Lopar was decimated by plague, while Komiza remained
      unaffected. Genotyping of the CCR5 polymorphism was performed using the
      polymerase chain reaction (PCR) method with primers flanking the region
      containing 32-bp deletion. RESULTS: The frequency of CCR5del32 in Lopar was 6.0%
      and in Komiza 1.5% (P=0.037). A previous study in 303 random Croatian blood
      donors showed a frequency of CCR5 32bp deletion of 7.1%. CONCLUSION: This study
      does not rule out the possible role of plague in positive selection at CCR5del32.
      However, analyses of further neighboring isolated island communities need to be
      made in order to provide more substantial support for this hypothesis.

PMID- 16909456
TI  - Metabolic syndrome in a metapopulation of Croatian island isolates.
AB  - AIM: To investigate the prevalence and factors associated with the metabolic
      syndrome in 9 isolated populations on Adriatic islands, Croatia, and in the group
      of immigrants to these islands. METHODS: Random samples of 100 inhabitants from
      each village and 101 immigrants were collected during 2002 and 2003. Bivariate
      and multivariate methods were used in data analysis. Age, gender, village, diet,
      smoking habits, physical activity, education, occupational class, and personal
      genetic history (a pedigree-based estimate of the individual genome-wide
      heterozygosity level) were used as independent variables in logistic regression.
      RESULTS: A total of 343 (34%) examinees met criteria of the metabolic syndrome
      diagnosis, with significant differences in the prevalence among villages
      (P=0.002). Metabolic syndrome was most frequently detected on Mljet island (53%),
      where all examinees exhibited fasting plasma glucose over 6.1 mmol/L. Examinees
      with metabolic syndrome were significantly older than those without it (median
      age 60.0 vs 53.0; P<0.001). Women were more frequently diagnosed than men (39% vs
      28%; P<0.001). The highest prevalence of the metabolic syndrome was found in the
      autochthonous group, whereas the lowest proportion was recorded in the admixed
      group (39% vs 21%, respectively, P=0.017). However, only age (odds ratio [OR],
      1.06; 95% confidence intervals [CI], 1.03-1.08) and having a university degree
      (OR, 0.18; 95% CI 0.04-0.92) were significantly associated with metabolic
      syndrome in the regression model. CONCLUSION: Metabolic syndrome was not
      associated with pedigree-based individual genome-wide heterozygosity estimate,
      after controlling for a number of confounding factors. More precise marker based
      genomic measures are needed to provide a clear answer whether metabolic syndrome
      development is influenced by the population genetic structure.

PMID- 16909457
TI  - Case-control study of risk factors for lumbar intervertebral disc herniation in
      Croatian island populations.
AB  - AIM: To investigate the risk factors for lumbar intervertebral disc herniation
      (L4/L5 or L5/S1) severe enough to require surgery of the lower spine among 9
      isolated populations of Croatian islands and to evaluate predictive value,
      sensitivity, and specificity of a simple screening test based on the
      understanding of the risk factors in this population. METHODS: In a sample of
      1001 examinees from Croatian island populations, we identified all subjects who
      underwent surgery of the lower spine due to lumbar intervertebral disc herniation
      L4/L5 or L5/S1 and selected 4 controls matched by age, gender, and village of
      residence for each of them. Odds ratio was computed for the following variables:
      body mass index, occupation, intensity of physical labor at work, intensity of
      physical labor at home, smoking index, claudication index, self-assessed
      limitation in physical activity, level of education, socio-economic status, and
      family history of lumbar intervertebral disc herniation requiring surgery.
      RESULTS: Comparison of 67 identified cases with 268 controls revealed the highest
      odds ratios (OR) for positive family history (OR 4.00; 95% confidence intervals
      [CI], 1.89-6.11, P<0.001), intensity of physical labor at work defined as (hard)
      (OR 2.94; 95% CI, 1.07-4.81, P<0.001), and body mass index of 25.7 or more (OR
      2.77, 95% CI, 1.05-4.49, P=0.002). A simple screening test based on the presence
      of any two of these three criteria has 74% sensitivity and 82% specificity to
      detect persons who underwent lower spine surgery due to lumbar intervertebral
      disc herniation in the population aged 40 years or more. CONCLUSION: Occurrence
      of lumbar disk herniation severe enough to require surgery of the lower spine can
      be predicted using a very simple set of criteria. This type of screening could
      reduce the need for surgery in isolated communities through prevention within
      primary health care.

PMID- 16909458
TI  - Effects of inbreeding, endogamy, genetic admixture, and outbreeding on human
      health: a (1001 Dalmatians) study.
AB  - AIM: (1001 Dalmatians) research program collects biomedical information from
      multiple small isolated populations ((metapopulation)) on Adriatic islands,
      Croatia, and investigates health effects of human population isolation,
      inbreeding, admixture, and outbreeding. METHODS: We collected random samples of
      100 individuals from 9 island settlements and an additional sample of 101
      immigrants to the islands, pooled from all study populations. According to their
      personal genetic histories, the examinees were categorized as inbred,
      autochthonous, admixed, and outbred. A total of 76 inbred individuals from a
      total sample of 1001 examinees were matched to 76 autochthonous, 76 admixed, and
      76 outbred controls by gender, age (+/-5 years), village of residence, education,
      and socio-economic status. We investigated the effects of presumed individual
      genome-wide heterozygosity predicted from personal genetic histories on the
      following 10 traits: systolic and diastolic blood pressure, body mass index, high
      and low density lipoproteins and total cholesterol, triglycerides, uric acid,
      creatinine, and blood glucose. RESULTS: Personal genetic history significantly
      affected systolic blood pressure (Spearman rho=0.157, P=0.006), while the effect
      on cholesterol (rho=0.105, P=0.069), and high density lipoprotein cholesterol
      (rho=0.104, P=0.071) was suggestive. Admixed individuals and immigrants
      consistently showed values associated with lower health risk. When inbred and
      autochthonous samples were merged and compared with the admixed and outbred
      samples to increase the power of the study, the effects on the three traits above
      and also on body mass index and diastolic blood pressure became statistically
      significant. The medians for all 10 medically relevant traits in inbred and
      autochthonous group, with lower values of presumed individual genome-wide
      heterozygosity, were less favorable in terms of health. CONCLUSION: The combined
      effects of founder effect, genetic drift, and inbreeding can increase the
      frequency of detrimental rare variants in human metapopulations, leading to
      overall worsening of population health, whereas admixture and outbreeding appear
      to have the opposite effect.

PMID- 16909459
TI  - Life expectancy and mortality differences between populations on Croatian islands
      and the mainland.
AB  - AIM: To examine the differences in life expectancy and mortality between the
      populations on Croatian islands and the mainland, and among the islands
      themselves. METHOD: Data on population size and mortality collected in Croatia in
      2001 were analyzed by life table and standardized mortality rates. RESULTS: Life
      expectancy at birth (95% confidence interval) of the population on Croatian
      islands was 76.4 yr (75.7-77.1) which was significantly higher than life
      expectancy at birth of general Croatian population which was 73.8 yr (73.5-73.9)
      or mainland Croatian population which was 73.7 yr (73.6-73.8). Island population
      had higher life expectancy until the age of 80 and again in the oldest age group,
      95+. More than 10% of inhabited islands in Croatia had life expectancy at birth
      over 80 years. Two inhabited islands, Ilovik (Kvarner islands) and Lopud (South
      Dalmatian islands), had one of the highest life expectancy at birth recorded in
      the literature, with 95.0 and 90.6 years respectively. Mortality rates on islands
      were significantly lower for age groups 50-64 and 65-79 years, and this
      difference persisted for all island groups compared with general Croatian
      population. CONCLUSION: Residents of Croatian islands had a higher life
      expectancy than general or mainland Croatian population. Life expectancy at birth
      on Croatian islands was lower than in other European Mediterranean countries, but
      it resembles that in the neighboring Slovenia, and it is considerably higher than
      in central and eastern Europe and Balkan countries.

PMID- 16909462
TI  - Mental health and health-related quality of life in Croatian island population.
AB  - AIM: To explore differences in self-perceived health as an indicator of health
      status and mortality, in six isolated populations from Croatian islands and to
      compare the results with control from general Croatian population obtained
      through the National Health Survey. METHOD: Health-related quality of life was
      measured using the Short Form Health Status Questionnaire (SF-36). The
      questionnaire was administered to 600 participants, inhabitants of 6 villages:
      Rab, Barbat, Lopar, and Supetarska Draga on island Rab, and Komiza and Vis, on
      island Vis, and to control group of 600 participants from the general Croatian
      population matched by age and gender to islanders. RESULTS: The islanders scored
      higher than controls on 3 out of 8 health dimensions, physical functioning
      (80.1+/-22.4 vs 73.2+/-24.8, P<0.001), vitality (61.0+/-20.3 vs 55.7+/-19.9,
      P<0.001), and pain (70.1+/-28.0 vs 65.9+/-26.5, P=0.008). Social functioning of
      islanders was significantly lower than in control group (73.4+/-18.6 vs 77.6+/
      23.4, P=0.001). There was also a significant variation in health status among the
      islanders according to the isolation level, with the largest differences in
      general health perception and mental health. High isolation group reported the
      lowest score of all groups on mental health (P=0.018), physical functioning
      (P=0.045), general health (P=0.001), and vitality dimension (P=0.027).
      CONCLUSION: Inhabitants of Croatian islands in general showed better health
      related functioning on the most of the health dimensions than general population.
      Islanders scored lower than controls only on social functioning which can be
      explained by their geographical isolation and small population. Low mental health
      score of islanders in the highly isolated group should be taken in account in
      planning health services for islands.

PMID- 16909461
TI  - Chronic respiratory symptoms in Croatian Adriatic island metapopulations.
AB  - AIM: To investigate the prevalence of chronic respiratory symptoms in 9
      metapopulations on Adriatic islands in Croatia, and the relationship between
      respiratory symptoms and individual genetic background. METHODS: We obtained
      random sample of 1001 adult inhabitants of 9 Adriatic island villages in Croatia,
      that also included immigrants to these villages. European Union respiratory
      health questionnaire and World Health Organization non-communicable diseases
      questionnaire were used. Personal genetic histories were reconstructed, based on
      the two-generation ancestral pedigrees. Bivariate and multivariate methods were
      used in the analysis. RESULTS: Women reported the occurrence of acute dyspnea
      (P=0.017), cough (P=0.002), and asthma (P=0.002) more often than men. Gender was
      the strongest predictor for acute and/or chronic cough (odds ratio [OR], 1.69;
      95% confidence interval [CI], 1.23-2.33) and asthma (OR, 2.00; 95% CI, 1.00
      4.01), whereas smoking was the strongest risk factor for acute and chronic
      dyspnea (OR, 1.90; 95% CI, 1.21-2.99) and airway narrowing (OR, 1.84; 95% CI,
      1.18-2.87). Residence on the northern islands increased the odds of allergy,
      whereas the highest odds ratio of 3.20 was associated with the interaction of
      northern residence and immigrant background. Genetic background was a significant
      predictor only for the occurrence of allergy symptoms. CONCLUSION: Differences in
      respiratory findings among the island inhabitants were often associated with
      smoking prevalence. Interaction of residence on northern Adriatic islands and
      immigrant background proved to be the strongest predictor for the occurrence of
      allergy symptoms. This study indicated that environmental factors played a very
      important role in the occurrence of respiratory symptoms.

PMID- 16909460
TI  - Body mass index and nutrition as determinants of health and disease in population
      of Croatian Adriatic islands.
AB  - AIM: To investigate the relationships between body mass index (BMI), dietary
      habits, and cardiovascular risk factors in isolated Adriatic island populations
      of Croatia. METHODS: Random sample of subjects (n=1001) was interviewed, using a
      validated questionnaire developed for this research program. Dietary habits were
      assessed on the basis of applied Food Frequency Questionnaire (FFQ). Biochemical
      analyses of total cholesterol, high density lipoprotein (HDL), low density
      lipoprotein (LDL), triglycerides, and blood glucose were performed. Blood
      pressure (mm Hg), height (m), and weight (kg) were measured following standard
      procedures. RESULTS: Out of 1001 study participants, 507 (50.7%) were overweight
      (247 [48.7%] men and 260 [51.3%] women), whereas 268 (26.8%) were obese (122
      [45.5%] men and 146 [54.5%] women). In both genders, there was a positive
      correlation between body mass index (BMI) and levels of triglycerides (P<0.001),
      glucose (P<0.001), diastolic blood pressure (P<0.001), and systolic blood
      pressure (male: P=0.002, female: P<0.001). Logistic regression showed that female
      gender (OR, 2.31; 95% CI, 1.61-3.31), overweight (OR, 1.97; 95% CI, 1.34-2.88),
      obesity (OR, 1.90; 95% CI, 1.22-2.96), more frequent consumption of meat (OR
      1.17; 95% CI, 1.06-1.30) and beer (OR 1.14; 95% CI, 1.03-1.27), and less frequent
      consumption of potatoes (OR 0.91; 95% CI, 0.83-0.99) were predictive for the
      presence of cardiovascular risk factors. CONCLUSION: Prevalence of obesity and
      related health outcomes was surprisingly high for the studied population. We
      found a correlation between BMI, dietary habits, and cardiovascular risk factors.

PMID- 16909463
TI  - Demonstrating reduced environmental and genetic diversity in human isolates by
      analysis of blood lipid levels.
AB  - AIM: To test the hypothesis that phenotypic diversity in isolated human
      populations is decreased in comparison with general outbred population because of
      reduced genetic and environmental diversity. To demonstrate this in populations
      for which reduced genetic and environmental diversity had already been
      established, by studying the amount of variation in plasma lipid levels. METHODS:
      Fasting plasma lipid levels (cholesterol, triglycerides, low density lipoprotein
      [LDL], and high density lipoprotein [HDL]) were measured in randomly selected 300
      inhabitants from 2 isolated human populations, the island of Rab and the
      neighboring islands of Vis and Lastovo, Croatia. The populations were chosen
      based on previous analyses of genetic diversity and lifestyle patterns, which
      were shown to be both less diverse and more uniform than the general Croatian
      population. We studied whether the 25'-75' and 5'-95' interpercentile ranges in
      observed values were consistently smaller in 2 samples of 300 examinees from
      isolated populations in comparison with nearly 6000 examinees from an earlier
      study who were demographically targeted to represent the larger Croatian
      population. RESULTS: General population had much wider range of observed values
      of triglycerides and HDL than both isolated populations. However, both isolated
      populations exhibited greater extent of variation in the levels of LDL, while the
      ranges of cholesterol values were similar. CONCLUSION: Although reduced genetic
      and environmental diversity in isolated human populations should necessarily
      reduce the variance in observed phenotypic values, it appears that specific
      population genetic processes in isolated populations could be acting to maintain
      the variation. Departure from the Hardy-Weinberg equilibrium due to
      consanguinity, sub-structuring and differentiation within the isolates, and
      increased rate of new mutations could theoretically explain this paradox.

PMID- 16909464
TI  - The meanings of health and its promotion.

PMID- 16909465
TI  - Every country or state needs two medical schools.

PMID- 16909466
TI  - Demonstration of a new biosensing concept for immunodiagnostic applications based
      on change in surface conductance of antibodies after biomolecular interactions.
AB  - We report an important observation that the surface conductivity of antibody
      layer immobilized on polylysine-coated glass substrate decreases upon the
      formation of complex with their specific antigens. This change in conductivity
      has been observed for both monoclonal and polyclonal antibodies. The conductance
      of monoclonal mouse IgG immobilized on polylysine-coated glass substrate changed
      from 1.02x10(-8) ohm(-1) to 1.41x10(-11) ohm(-1) at 10 V when complex is formed
      due to the specific biomolecular interactions with rabbit anti-mouse IgG
      F(ab')(2). Similar behavior was observed when the same set up was tested in two
      clinical assays: (1) anti-Leishmania antigen polyclonal antibodies taken from
      Kala Azar positive patient serum interacting with Leishmania promastigote
      antigen, and (2) anti-p21 polyclonal antibodies interacting with p21 antigen. The
      proposed concept can represent a new immunodiagnostic technique and may have wide
      ranging applications in biosensors and nanobiotechnology too.

PMID- 16909467
TI  - Nutritional status of four species of giant land snails in Nigeria.
AB  - Four species of African giant land snails (Archachatina marginata (ovum)
      Pfeiffer, Archachatina marginata (saturalis) Philippi, Achatina achatina and
      Limicolaria spp.) were assessed for their proximate and mineral compositions
      aimed at establishing their nutritive values on wet weight basis. Analysis of
      muscle revealed that composition of crude protein varied from 18.66%+/-0.57% in
      Limicolaria spp. and 20.56%+/-0.05% in Archachatina marginata (ovum) Pfeiffer;
      moisture content was 76.56%+/-0.04% in Archachatina marginata (ovum) Pfeiffer and
      78.68%+/-0.68% in Limicolaria spp. and ash was 1.34%+/-0.02% in Achatina achatina
      and 1.44%+/-0.01% in Archachatina marginata (ovum) Pfeiffer. These values were
      statistically different from each other (P<0.05). Carbohydrate and fat content
      were generally low. Crude fibre was not detected in any of the species. The
      concentrations of zinc, iron, manganese, magnesium, calcium, phosphorus, sulphur,
      potassium and sodium in the flesh of the snails were determined. Values of iron,
      magnesium, calcium, phosphorus, potassium and sodium were consistently high while
      cobalt, copper and lead were not detected. Snails complement the required trace
      and minor elements needed for proper growth and development in human being, so it
      is recommended for regular consumption.

PMID- 16909468
TI  - Effect of selected fungi on the reduction of gossypol levels and nutritional
      value during solid substrate fermentation of cottonseed meal.
AB  - The objective of this work was to investigate the effect of six individual
      strains of fungi on the reduction of gossypol levels and nutritional value during
      solid substrate fermentation of cottonseed meal (CSM). Six groups of disinfected
      CSM substrate were incubated for 48 h after inoculation with either of the fungi
      C. capsuligena ZD-1, C. tropicalis ZD-3, S. cerevisae ZD-5, A. terricola ZD-6, A.
      oryzae ZD-7, or A. niger ZD-8. One not inoculated group (substrate) was used as a
      control. Levels of initial and final free gossypol (FG), crude protein (CP),
      amino acids (AA) and in vitro digestibility were assayed. The experiment was done
      in triplicate. The experimental results indicated that microbial fermentation
      could greatly decrease (P<0.05) FG levels in CSM. The detoxification efficiency
      differed between the species of microorganisms applied. From the perspective of
      reducing CSM potential toxicity, C. tropicalis ZD-3 was most successful followed
      by S. cerevisae ZD-5 and A. niger ZD8. They could reduce FG levels of CSM to
      29.8, 63.07 and 81.50 mg/kg based on DM (dry matter), respectively, and their
      detoxification rate were 94.57%, 88.51% and 85.16%, respectively. If crude
      protein, amino acids content and their in vitro digestibility were also taken
      into account, A. niger ZD-8 may be the best choice. The CP content of CSM
      substrate fermented by C. tropicalis ZD-3 and A. niger ZD-8 were improved by
      10.76% and 22.24%; the TAA (total amino acids) contents were increased by 7.06%
      and 11.46%, and the EAA (essential amino acids) were raised by 7.77% and 12.64%,
      respectively. Especially, the levels of methionine, lysine and threonine were
      improved greatly (P<0.05). The in vitro CP digestibility of CSM fermented by C.
      tropicalis ZD-3 and A. niger ZD-8 was improved by 13.42% and 18.22%, the TAA were
      increased by 17.75% and 22.88%, and the EAA by 16.61% and 21.01%, respectively.
      In addition, the in vitro digestibility of methionine, lysine and threonine was
      also improved greatly (P<0.05).

PMID- 16909471
TI  - Essential oil of Actinidia macrosperma, a catnip response kiwi endemic to China.
AB  - OBJECTIVE: To identify compounds that may be responsible for catnip response of
      Actinidia macrosperma, and compare chemical compositions in the wild and in vitro
      regenerated plants. METHODS: GC-MS and relative retention indices with n-alkanes
      as reference points were used for compound identification, and component relative
      percentage was calculated based on GC peak areas without using correction
      factors. RESULTS: There are 28 compounds (92.72%) and 15 compounds (93.88%)
      identified in the essential oils from the wild and regenerated plants,
      respectively. Dihydronepetalactone, iridomyrmecin, and dihydroactinidiolide,
      which are believed to be attractive to felines, are present in both wild and
      regenerated plants. Actinine was not detected, and beta-pheylethyl alcohol was
      only present in wild plant. In addition, short-chain enol derivatives, messengers
      in chemical communication, are commonly present in wild plant of A. macrosperma,
      but absent in regenerated one. CONCLUSION: Dihydronepetalactone, iridomyrmecin,
      and dihydroactinidiolide are responsible for the catnip response of A.
      macrosperma.

PMID- 16909469
TI  - Yield and quality responses of citrus (Citrus reticulate) and tea (Podocarpus
      fleuryi Hickel.) to compound fertilizers.
AB  - Experiments were carried out with citrus (Citrus reticulate) and tea (Podocarpus
      fleuryi Hickel.) to study the effects of compound fertilizers on their yields and
      quality. In the citrus experiment, application of compound fertilizers increased
      available P, K and Mg contents in soil but decreased alkali-hydrolyzable N
      contents in soil and N, P and K contents in leaves. In the tea experiment,
      application of compound fertilizers increased available P, K and Mg contents in
      soil and N, P, K and Mg contents in leaves but decreased alkali-hydrolyzable N in
      soil compared with the urea treatment. Application of compound fertilizers could
      improve the quality of citrus and tea, increase their yields and enhance their
      economical profits significantly. Compared with the control, application of
      compound fertilizers increased citrus yields by 6.31, 12.94 and 17.69 t/ha, and
      those of tea by 0.51, 0.86 and 1.30 t/ha, respectively. Correspondingly, profits
      were increased by 21.4% to 61.1% for citrus and by 10.0% to 15.7% for tea.
      Optimal rates of compound fertilizers were recommended for both crops.

PMID- 16909470
TI  - Enhanced degradation of carbon tetrachloride by surfactant-modified zero-valent
      iron.
AB  - Sorption of carbon tetrachloride (CT) by zero-valent iron (ZVI) is the rate
      limiting step in the degradation of CT, so the sorption capacity of ZVI is of
      great importance. This experiment was aimed at enhancing the sorption of CT by
      ZVI and the degradation rate of CT by modification of surfactants. This study
      showed that ZVI modified by cationic surfactants has favorable synergistic effect
      on the degradation of CT. The CT degradation rate of ZVI modified by cetyl
      pyridinium bromide (CPB) was higher than that of the unmodified ZVI by 130%, and
      the CT degradation rate of ZVI modified by cetyl trimethyl ammonium bromide
      (CTAB) was higher than that of the unmodified ZVI by 81%. This study also showed
      that the best degradation effect is obtained at the near critical micelle
      concentrations (CMC) and that high loaded cationic surfactant does not have good
      synergistic effect on the degradation due to its hydrophilicity and the block in
      surface reduction sites. Furthermore degradation of CT by ZVI modified by
      nonionic surfactant has not positive effect on the degradation as the ionic
      surfactant and the ZVI modified by anionic surfactant has hardly any obvious
      effects on the degradation.

PMID- 16909472
TI  - Conservation of indigenous medicinal botanicals in Ekiti State, Nigeria.
AB  - The rapid appraisal method was used to identify the botanicals used
      ethnomedicinally from a total of 300 randomly selected respondents drawn from the
      existing three geo-political zones of Ekiti State, Nigeria. The results obtained
      revealed that about 40% of the 71 botanicals identified presently rare. Most of
      the presently abundant botanicals are species primarily cultivated for other
      purpose other than medicine. Most of the identified species are valued for their
      curative effects on malaria and fever, the predominant diseases in the study
      area. The need for the conservation of the rare species cannot be over emphasised
      as most rural dwellers in the study area depend mostly on herbs from these
      species. Strategies towards the attainment of this goal are proposed.

PMID- 16909473
TI  - Successful immunological treatment of gallbladder cancer in India--case report.
AB  - Gallbladder cancer has a poor outcome because of its anatomy and location. Often,
      the diagnosis is made very late due to its silent course. Post-operated cases do
      respond to chemotherapy but the survival is counted in months and the quality of
      life is further hampered due to toxicity of drugs. Immunotherapy holds good
      promise in non-responding cancers treated by conventional chemotherapeutic
      agents. Among various therapies, dendritic cell therapy is growing at rapid pace
      due to its acceptable rationale. It has been utilized in treating successfully
      resected stage III (T2, N1, M0) gallbladder cancer in one of our patients. A 48
      years old lady treated with this therapy is free of metastasis with ten doses of
      autologous dendritic cell vaccine constructed by utilizing resected tumor lysate
      antigen. She has received ten doses of therapy in 14 months of her treatment.
      This therapy has proven to be safe and without apparent side effects. The
      positive clinical response obtained supports that autologous dendritic cell-based
      immunotherapy is a promising therapeutic approach for refractory gallbladder
      cancers.

PMID- 16909474
TI  - Carvedilol protected diabetic rat hearts via reducing oxidative stress.
AB  - Oxidative stress plays a dominant role in the pathogenesis of diabetes mellitus.
      Bcl-2 gene has close connection with antioxidant stress destruction in many
      diseases including diabetes. Carvedilol, an adrenoceptor blocker, also has
      antioxidant properties. To study the effect of carvedilol on the antioxidant
      status in diabetic hearts, we investigated carvedilol-administrated healthy and
      streptozotocin-induced diabetic rats. After small and large dosage carvedilol
      administered for 5 weeks, hemodynamic parameters, the levels of malondialdehyde,
      activities of antioxidant enzymes and expression of Bcl-2 mRNA in the cardiac
      tissues were measured. The diabetic rats not only had cardiac disfunction, weaker
      activities of antioxidant enzymes, but also showed lower expression of Bcl-2.
      Carvedilol treatment increased activities of antioxidant enzymes and expression
      of Bcl-2 in healthy rats as well as diabetic rats. These results indicated that
      carvedilol partly improves cardiac function via its antioxidant properties in
      diabetic rats.

PMID- 16909475
TI  - Non-occupational lead exposure and hypertension in Pakistani adults.
AB  - Hypertension is one of the most prevalent diseases in the developed and
      developing countries. Based on the long historical association and the
      provocative findings of blood pressure effects at low level of lead exposure a
      study was carried out to determine if an association existed between low blood
      lead concentration and hypertension. In this study the effects of low-level
      exposure to lead on blood pressure were examined among 244 adults using atomic
      absorption spectrometer. For quality assurance purpose certified reference
      materials i.e., Animal blood A-13, Bovine liver 1577 and cotton cellulose V-9
      from IAEA (International Atomic Energy Agency) and NIST (National Institute of
      Standard Technology) were analyzed under identical experimental conditions. The
      mean age of hypertensive adults was 52 years (range 43 - 66). The mean values of
      systolic and diastolic blood pressure were (209+/-11.7) (range 170 - 250) and
      (117+/-3.9) (range 105 - 140) mmHg respectively. Blood lead concentration ranged
      from 78 - 201 microg/L with a mean of 139 microg/L and 165 - 497 microg/L with a
      mean of 255 microg/L in normal and hypertensive adults respectively. Increase in
      systolic blood pressure was significantly predictive with increase in blood lead
      levels. Body mass index (BMI) and lipid profile including total cholesterol, low
      density lipoprotein cholesterol, high density lipoprotein cholesterol and
      triglyceride correlated with blood pressure.

PMID- 16909476
TI  - Dynamics of vascular volume and hemodilution of lactated Ringer's solution in
      patients during induction of general and epidural anesthesia.
AB  - OBJECTIVE: To investigate the dynamics of vascular volume and the plasma dilution
      of lactated Ringer's solution in patients during the induction of general and
      epidural anesthesia. METHODS: The hemodilution of i.v. infusion of 1000 ml of
      lactated Ringer's solution over 60 min was studied in patients undergoing general
      (n=31) and epidural (n=22) anesthesia. Heart rate, arterial blood pressure and
      hemoglobin (Hb) concentration were measured every 5 min during the study. Surgery
      was not started until the study period had been completed. RESULTS: General
      anesthesia caused the greater decrease of mean arterial blood pressure (MAP)
      (mean 15% versus 9%; P<0.01) and thereby followed by a more pronounced plasma
      dilution, blood volume expansion (VE) and blood volume expansion efficiency
      (VEE). A strong linear correlation between hemodilution and the reduction in MAP
      (r=-0.50; P<0.01) was found. At the end of infusion, patients undergoing general
      anesthesia retained 47% (SD 19%) of the infused fluid in the circulation, while
      epidural anesthesia retained 29% (SD 13%) (P<0.001). Correspondingly, a fewer
      urine output (mean 89 ml versus 156 ml; P<0.05) and extravascular expansion (454
      ml versus 551 ml; P<0.05) were found during general anesthesia. CONCLUSION: We
      concluded that the induction of general anesthesia caused more hemodilution,
      volume expansion and volume expansion efficiency than epidural anesthesia, which
      was triggered only by the lower MAP.

PMID- 16909477
TI  - Surveillance of viral contamination of invasive medical instruments in dentistry.
AB  - OBJECTIVE: To investigate the viral contamination of invasive medical instruments
      in dentistry and to provide health administrative institutions with surveillance
      data. METHODS: Sterilized samples were randomly collected from the department of
      dentistry to detect HBV-DNA, HCV-RNA, HIV-RNA and HBsAg. RESULTS: Of the invasive
      medical instruments that were sterilized with 2% glutaraldehyde, one of the
      samples was positive for HBV-DNA, and another sample was positive for HBsAg.
      CONCLUSION: Though massive virus contamination of invasive medical instruments in
      dentistry has been reduced to a low level, the occurrence of contamination still
      remains.

PMID- 16909479
TI  - Effects of levobupivacaine and bupivacaine on rat myometrium.
AB  - OBJECTIVE: To study the effect of levobupivacaine and bupivacaine on the
      contractility of isolated uterine muscle strips from pregnant and non-pregnant
      female rats. METHODS: Full-thick myometrial strips were prepared from 18- to 21
      day pregnant (n=8) and non-pregnant rats (n=7). After contractions became
      regular, strips were exposed to cumulative concentrations of the two drugs from
      10(-8) to 10(-4) mol/L, amplitude and frequency of the uterine contraction was
      recorded. RESULTS: Two local anesthetics caused a concentration dependent
      inhibition on contractility of myometrial strips from pregnant and non-pregnant
      rats. In the myometrium from non-pregnant rats, -logIC(50) of levobupivacaine and
      bupivacaine were 4.85 and 4.25 respectively. In the myometrium from pregnant
      rats, similar concentrations of levobupivacaine and bupivacaine were observed, 
      logIC(50) were 2.7 and 2.9 respectively. Levobupivacaine produced an increase in
      amplitude of contractions, while bupivacaine showed an increased trend in
      frequency. CONCLUSION: These results demonstrate that levobupivacaine and
      bupivacaine may inhibit myometrium contractility. The inhibitory effect of
      levobupivacaine or bupivacaine is not enhanced by gestation in rat.
      Levobupivacaine may have more positive influence than bupivacaine in pregnant
      myometrium.

PMID- 16909478
TI  - Edaravone protects PC12 cells from ischemic-like injury via attenuating the
      damage to mitochondria.
AB  - BACKGROUND: Edaravone had been validated to effectively protect against ischemic
      injuries. In this study, we investigated the protective effect of edaravone by
      observing the effects on anti-apoptosis, regulation of Bcl-2/Bax protein
      expression and recovering from damage to mitochondria after OGD (oxygen-glucose
      deprivation)-reperfusion. METHODS: Viability of PC12 cells which were injured at
      different time of OGD injury, was quantified by measuring MTT (2-(4,5
      dimethylthia-zol-2-yl)-2,5-diphenyltetrazolium bromide) staining. In addition,
      PC12 cells' viability was also quantified after their preincubation in different
      concentration of edaravone for 30 min followed by (OGD). Furthermore, apoptotic
      population of PC12 cells that reinsulted from OGD-reperfusion with or without
      preincubation with edaravone was determined by flow cytometer analysis, electron
      microscope and Hoechst/PI staining. Finally, change of Bcl-2/Bax protein
      expression was detected by Western blot. RESULTS: (1) The viability of PC12 cells
      decreased with time (1 - 12 h) after OGD. We regarded the model of OGD 2 h, then
      replacing DMEM (Dulbecco's Modified Eagle's Medium) for another 24 h as an OGD
      reperfusion in this research. Furthermore, most PC12 cells were in the state of
      apoptosis after OGD-reperfusion. (2) The viability of PC12 cells preincubated
      with edaravone at high concentrations (1, 0.1, 0.01 micromol/L) increased
      significantly with edaravone protecting PC12 cells from apoptosis after OGD
      reperfusion injury. (3) Furthermore, edaravone attenuates the damage of OGD
      reperfusion on mitochondria and regulated Bcl-2/Bax protein imbalance expression
      after OGD-reperfusion. CONCLUSION: Neuroprotective effects of edaravone on
      ischemic or other brain injuries may be partly mediated through inhibition of Bcl
      2/Bax apoptotic pathways by recovering from the damage of mitochondria.

PMID- 16909480
TI  - Basal or bolus dose, which is the key factor in CSII?
AB  - OBJECTIVE: To observe the value of HbA(1)c level evaluating the total daily basal
      insulin dose by continuous subcutaneous insulin infusion (CSII) in 268 patients
      with type 2 diabetes mellitus. METHODS: 5-point capillary blood glucose was
      monitored in pre- and post-CSII and the insulin dose which could stabilize blood
      glucose was defined as the total daily dose of insulin, including basal and bolus
      total dose. Correlation between HbA(1)c level and total daily dose of insulin in
      patients with type 2 diabetes mellitus was analyzed. Correlation between HbA(1)c
      level and 5-point capillary blood glucose was also analyzed. RESULTS: Obvious
      correlation was observed between HbA(1)c level and the basal total daily dose of
      insulin if HbA(1)c was more than 9.3% (r=0.635, P<0.05). The average of 5-point
      capillary blood glucose was best correlated with HbA(1)c and fasting blood
      glucose next best. CONCLUSION: HbA(1)c level can forecast basal total daily dose
      of insulin in CSII.

PMID- 16909483
TI  - Safer fruits and vegetables.

PMID- 16909482
TI  - New vaccine for infants.

PMID- 16909481
TI  - Brain natriuretic peptide: a potential indicator of cardiomyogenesis after
      autologous mesenchymal stem cell transplantation?
AB  - We observed in a pilot study that there was a transient elevation of brain
      natriuretic peptide (BNP) level shortly after the transplantation in the patient
      with ischemic heart failure, which is unexplainable by the simultaneous increase
      of the cardiac output and six-minute walk distance. Similar findings were
      observed in the phase I trial. We postulated on the basis of the finding of
      Fukuda in vitro that this transient elevation of BNP level against the
      improvement of cardiac function and exercise capacity might indicate
      cardiomyogenesis in patients after mesenchymal stem cell transplantation. Further
      study is warranted to verify the hypothesis.

PMID- 16909484
TI  - First depression patch approved.

PMID- 16909485
TI  - First generic Flonase.

PMID- 16909487
TI  - Guidance on 'whole grain'.

PMID- 16909486
TI  - Modernizing medical product development through collaboration.

PMID- 16909489
TI  - Stem cell work gets states' aid after Bush veto.

PMID- 16909488
TI  - Treatment for head and neck cancer.

PMID- 16909491
TI  - Senate removes abortion option for young girls.

PMID- 16909492
TI  - Drug makers pay for lunch as they pitch.

PMID- 16909490
TI  - Correcting the errors of disclosure.

PMID- 16909493
TI  - Growing debate as doctors train on new devices.

PMID- 16909494
TI  - F.D.A. shifts view on next-day pill; moves toward backing its sale over the
      counter.

PMID- 16909495
TI  - Inquiries in Britain uncover loopholes in drug trials.

PMID- 16909496
TI  - FDA to weigh using fake blood in trauma trial.

PMID- 16909497
TI  - Financial ties to industry cloud major depression study; at issue: whether it's
      safe for pregnant women to stay on medication; JAMA asks author to explain.

PMID- 16909498
TI  - JAMA to toughen rules on author disclosure.

PMID- 16909499
TI  - Medical reviews face criticism over lapses.

PMID- 16909500
TI  - Gates won't fund AIDS researchers unless they pool data.

PMID- 16909501
TI  - Seizures of Canadian drugs rise as Congress, Customs spar.

PMID- 16909502
TI  - USA confronts looming organ-shortage crisis.

PMID- 16909503
TI  - Fentanyl-laced street drugs "kill hundreds".

PMID- 16909504
TI  - Trial blazers.

PMID- 16909505
TI  - [Nina Abramovna Verzhbinskaia (on her 100th birthday)].

PMID- 16909506
TI  - Rage against the machine. Anti-politics and the AIDS epidemic.

PMID- 16909508
TI  - FDA hearing on home HIV testing.

PMID- 16909507
TI  - Questions, questions. The future of HIV research.

PMID- 16909509
TI  - ARV birth defect risks.

PMID- 16909511
TI  - Who are the elite controllers?

PMID- 16909510
TI  - HSV-2 suppression reduces HIV and HSV shedding.

PMID- 16909512
TI  - [Heart failure mortality in Spain: is there an andalusian paradox?].
AB  - Congestive heart failure has a high mortality, as reflected in different clinical
      trials and observational studies. Spain, as other countries around the
      Mediterranean basin, have a relatively low rate of coronary deaths, attributed to
      the so-called Mediterranean lifestyle. Andalusia, in the southern most part of
      Spain, constitutes the paradigm of Mediterranean lifestyle. However, different
      reports show that the prevalence of ischemic heart disease is higher in Andalusia
      than in other zones of Spain. Thus the mortality rate due to heart failure in
      Spain in the year 2000 per 100,000 inhabitants was 27.3 in men and 28.88 in women
      and each one of the eight Andalusia provinces had greater rates than the national
      mean in both men and woman. Even in countries with a relatively low prevalence of
      coronary heart disease as is the case in Spain, heart failure mortality seems to
      be parallel to local differences in IHD prevalence.

PMID- 16909513
TI  - Guidelines and algorithms for anxiety disorders: evidence-based excellence or
      garbage in, garbage out?

PMID- 16909515
TI  - Preauricular swelling: commentary. Diagnosis: chronic mastoiditis.

PMID- 16909517
TI  - The role of root resection in the age of dental implants.

PMID- 16909518
TI  - Recognizing the dental-medical symbiosis: back to basic sciences.

PMID- 16909516
TI  - A review of acupuncture clinical trials indexed during 2005.

PMID- 16909519
TI  - Fracture resistance and fracture resistance after fatigue loading of 4 different
      post and cores in endodontically treated teeth.
AB  - This article discusses the fracture resistance of 4 post and core systems
      including a combined obturator/post system before and after fatigue loading. The
      obturator/post demonstrated the highest fracture resistance values. The use of a
      combined obturator/post with a single resin endodontic sealer/luting cement seems
      promising.

PMID- 16909522
TI  - Lead your practice like a CEO.

PMID- 16909521
TI  - Implant-retained overdenture design for the malpositioned mandibular implants.
AB  - In the rehabilitation of the edentulous mandible, implant-retained overdenture
      represents a viable and cost-effective treatment. Successful prosthetic
      integration of this treatment relies on the accurate 3-dimensional position and
      angulation of the implant fixtures. If these requirements are not fulfilled,
      implant malposition occurs and negative effects on the function, esthetics, and
      structural integrity of the prosthesis may follow. Implant malposition commonly
      results from poor planning, surgical error, inaccuracies in the
      radiographic/surgical template fabrication, and the instability of the template
      during surgery. Potential solutions for implant malposition include surgical re
      treatment or prosthetic compensation in the form of an altered design of the
      final prosthesis. This article presents a prosthetic design of an overdenture for
      malpositioned implants in the anteroposterior plane. Prosthetic compensations
      included relocating the attachment mechanism into the bulk of the overdenture
      with the help of an interconnecting implant bar and a metal reinforcing framework
      for the overdenture.

PMID- 16909523
TI  - [Characteristics of transient evoked otoacoustic emissions in newborn hearing
      screening program].
AB  - BACKGROUND: Otoacoustic emissions (OAE) are considered the main instrument of the
      Newborn Hearing Screening Program (NHSP). AIM: To analyze the OAE of newborns
      evaluated in the NHSP. METHOD: Transient evoked OAE recordings were captured in
      1000 infants. The data were analyzed using the analysis of multivaried variance
      (Manova). RESULTS: Reference tables were calculated for the over all OAE levels
      and for frequency bands, according to gender and ear. The duration of the exam in
      the nursery was shorter than in the clinic. CONCLUSION: The level of the OAE was
      influenced by gender and ear, except for 0,7kHz. However, there were no observed
      differences between neonates without and with auditory risk.

PMID- 16909520
TI  - Clinical features of cinnamon-induced contact stomatitis.
AB  - Cinnamon flavoring agents are known to act on the mucosa as irritants or
      sensitizers. The objective of this study was to report on clinical and histologic
      features important in the diagnosis of cinnamon-induced contact stomatitis. We
      examined 37 past cases of contact stomatitis and identified clinical signs and
      symptoms and possible causes. The most common cause in the 37 cases was
      toothpaste; other causes were chewing gum and foods. Although various clinical
      findings were observed, some characteristics were evident. The most commonly
      affected site was the gingiva, which showed diffuse or generalized erythema and
      epithelial sloughing. It is important to identify the causative agents of such a
      disorder by understanding characteristic signs and symptoms and conducting an
      appropriate inquiry.

PMID- 16909524
TI  - [Breastfeeding of premature babies with less than 1500g: oral motor functioning
      and attachment].
AB  - BACKGROUND: Breastfeeding of premature babies. AIM: To describe breastfeeding in
      premature babies with very low birth weight (VLBW) and its association with the
      oral motor system (OMS) and with maternal-child bonding. METHOD: A cross
      sectional study with 48 VLBW premature babies. An interview with the mothers, as
      well as the evaluation of the newborns' OMS and signs of attachment was
      performed. Data was submitted to a descriptive analysis and to the Fischer Test.
      RESULTS: Variables that showed statistical association with nutritive sucking
      were: child's position at breast; nipple grasping; sucking coordination between
      sucking, breathing and swallowing; strength and maintenance; rhythm, and level of
      conscious. Twelve pair situations presented signs possible bonding problems.
      CONCLUSION: Components of OMS are associated to the quality of feeding of
      premature babies. This fact suggests that the early evaluation of breastfeeding
      can detect difficulties that could jeopardize adequate nutrition.

PMID- 16909525
TI  - [Auditory processing and high frequency audiometry in students of Sao Paulo].
AB  - BACKGROUND: Auditory processing and auditory sensibility to high Frequency
      sounds. AIM: To characterize the localization processes, temporal ordering,
      hearing patterns and detection of high frequency sounds, looking for possible
      relations between these factors. METHOD: 32 hearing fourth grade students, born
      in city of Sao Paulo, were submitted to: a simplified evaluation of the auditory
      processing; duration pattern test; high frequency audiometry. RESULTS: Three
      (9,4%) individuals presented auditory processing disorder (APD) and in one of
      them there was the coexistence of lower hearing thresholds in high frequency
      audiometry. CONCLUSION: APD associated to an auditory sensibility loss in high
      frequencies should be further investigated.

PMID- 16909527
TI  - [Phonological awareness therapy in the literacy process].
AB  - BACKGROUND: Phonological awareness and literacy. AIM: to verify the influence of
      phonological awareness therapy in the literacy process. METHOD: 46 children were
      submitted to an assessment involving the reading and writing of words and non
      words and of phonological awareness. The experimental group was submitted to
      therapy. RESULTS: Therapy had a positive influence in the performance of the
      children in the experimental group (76.47%) regarding tasks of phonological
      awareness and regarding their performance in reading and writing; only literate
      children were able to perform tasks involving phonemic awareness. CONCLUSION:
      Phonological awareness therapy facilitates the acquisition of the alphabetic
      code.

PMID- 16909528
TI  - [Severity of phonological disorders: perceptual judgment and percentage of
      correct consonants].
AB  - BACKGROUND: Phonological disorder. AIM: To apply the percentage of correct
      consonant (PCC) index and to verify the correlation between this index and the
      one applied perceptually by judges. METHOD: The PCC index of 50 phonological
      disordered subjects was calculated, after 60 judges heard the phonological tests
      for each subject and perceptually attributed the severity. RESULTS: The PCC index
      varied from 40% to 98%, with the predominant classification of the population in
      the mild and mild-moderate levels. CONCLUSION: A correlation between the
      perceptual judgment and the PCC indexes exists.

PMID- 16909526
TI  - [Oral communication of laryngectomized patients with tracheoesophageal
      prosthesis: pre and post-treatment comparative analysis].
AB  - BACKGROUND: Speech and voice training for laryngectomized patients with
      tracheoesophageal prosthesis. AIM: to compare the quality of oral communication
      of a group of laryngectomized patients with tracheoesophageal prostheses, pre and
      post speech and voice training. METHOD: Voice and speech samples of 17
      laryngectomized patients were analyzed before and after receiving speech and
      voice training. The voice and speech samples were mixed and presented to speech
      language pathologists for assessment. RESULTS: Statistically significant
      (Binomial Test) improvement was observed. CONCLUSION: It can be concluded that
      the proposed training improved the speech patterns, including melody and singing.

PMID- 16909529
TI  - [Phonological awareness improvement in primary school students].
AB  - BACKGROUND: Phonological awareness in primary school students. AIM: To verify the
      improvement of phonological awareness in primary school students after a speech
      and language stimulation program. METHOD: 20 students with the worst results in
      the first literacy exam were selected. Phonological awareness tests were analyzed
      at the beginning and at the end of the stimulation program. RESULTS: Most of the
      subjects demonstrated to have a notion about phonological awareness activities.
      CONCLUSION: Students demonstrated improvement, suggesting the effectiveness of
      the program.

PMID- 16909531
TI  - [Mime functional evaluation in facial paralysis following a stroke].
AB  - BACKGROUND: Functional evaluation of the facial movements in patients with facial
      paralysis following a stroke. AIM: To evaluate the function of the facial muscles
      of patients after central facial paralysis following a stroke. METHOD: Nine
      patients referred by the Neurology Service were evaluated. The evaluation focused
      on spontaneous, voluntary and reflex movements. RESULTS: Reflex and voluntary
      movement of the eyelid and forehead were preserved in all patients. However,
      spontaneous and voluntary movements of the lips and nose were limited according
      to the location and extension of lesion. CONCLUSION: The symptoms of central
      facial paralysis, in which paralysis only of voluntary movements of the lower two
      thirds of the face is expected, occurred in the minority of the patients.

PMID- 16909530
TI  - [Specific language impairment in adolescents: a follow-up case study].
AB  - BACKGROUND: A follow-up study of an individual with Specific Language Impairment.
      AIM: To describe the oral and written language development of an adolescent
      during 13 years of intervention. METHOD: A Male subject, 16 years old, in the
      second year of high school, who was assessed during the years with different
      language and auditory procedures. RESULTS: The Subject still presents oral and
      written language deficits, but these do not compromise intelligibility in any
      level. CONCLUSION: The studied subject presented significant language development
      during the therapeutic process. However, corroborating with other literature
      data, deficits still remain.

PMID- 16909532
TI  - [Macrosomia and auditory abilities: a comparative study].
AB  - BACKGROUND: Macrosomia is the positive deviation of normal growing standards.
      AIM: Due to the lack of studies related to the auditory abilities in macrosomic
      syndromes, the aim of the present study was to verify and compare the auditory
      abilities of two patients and to correlate these results with other complementary
      findings. METHOD: Anamneses, hearing, language, psychologic and neuroimage
      evaluation in two female subjects, eight and seventeen years old. RESULTS:
      Subject I - normal; subject II - impaired. CONCLUSION: There is a growing need
      for more investigations of the neurophysiology of the auditory system in this
      population. Studies in the area of hearing can favor the early diagnosis and
      therefore the intervention process.

PMID- 16909534
TI  - [Vocal rehabilitation in patients with Parkinson disease: interfering factors].
AB  - BACKGROUND: Vocal rehabilitation of patients with idiopathic Parkinson disease.
      AIM: To describe the interfering factors in the vocal rehabilitation of five
      individuals with Parkinson disease and to present the modifications in the oral
      communication. METHOD: Interviews and pre and post vocal treatment assessments
      were carried out using the Lee Silverman Voice treatment method (LVSTO). RESULTS:
      Articulation improvement was observed, as well as improvements in the vocal
      loudness and quality, generating satisfaction among the patients and family.
      CONCLUSION: The analyses of factors that contributed to the therapy process or
      made it difficult indicate aspects that must be taken into consideration to
      obtain effective results.

PMID- 16909533
TI  - [Adaptation of the picture exchange communication system in a school context].
AB  - BACKGROUND: Alternative communication. AIM: To evaluate the efficacy of the
      adapted Pecs and Picture Communication Symbols (PCS) in the communication of a
      child with cerebral palsy. METHOD: The participant of this study was a 9 year and
      10 months old girl, with athetoid quadriplegia. All stages of the adapted Pecs
      were applied (Walter, 2000), using the PCS pictures (Johnson, 1998), associated
      with the functional curriculum proposed by LeBlanc (1991). An experimental AB
      Design was used in order to test the procedures. RESULTS: The subject was able to
      pass through all of the adapted Pecs phases and to use her communication board in
      school activities. CONCLUSION: The adapted Pecs proved to be effective in
      improving the subject's communication abilities.

PMID- 16909537
TI  - [Guidelines on good publication practice: the committe on publication ethics
      (COPE) report 2003].

PMID- 16909535
TI  - [Noise and its interference over students in a classroom environment: literature
      review].
AB  - BACKGROUND: Influence of the acoustic environment on learning. AIM: To analyze
      the possible alterations students of schools found under the impact of internal
      or external noises may present. METHOD: Literature review on the following
      subjects: auditory processing, speech perception, acoustics of classrooms and
      basic notions about noise. CONCLUSION: Schools are under the impact of varied
      noises that can become invisible opponents to the learning process, especially in
      a place where the listening situation must be privileged. Audiologists can be
      part of a multidisciplinary team, helping to monitor these areas and helping to
      implement hearing conservation programs.

PMID- 16909536
TI  - [Proposal for velopharyngeal function rating in a speech perceptual assessment].
AB  - BACKGROUND: The perceptual assessment of velopharyngeal function during speech
      presents some limitations due to its subjectivity. AIM: To propose a method for
      velopharyngeal function rating based on hypernasality, nasal air emission and
      compensatory articulation deficits scores. CONCLUSION: The proposed method shows
      several advantages in terms of clinical and research documentation and for an
      adequate follow-up of therapeutic and surgical outcomes.

PMID- 16909539
TI  - Data on wildlife trade.

PMID- 16909538
TI  - Conservation Biology at twenty.

PMID- 16909540
TI  - Effects of a problem-based learning approach on attitude change and science and
      policy content knowledge.

PMID- 16909541
TI  - An anthropological perspective on some unexpected consequences of protected
      areas.

PMID- 16909542
TI  - Opposing views of the "ecosystem approach" to fisheries management.

PMID- 16909543
TI  - Conservation options for the Baiji: time for realism?

PMID- 16909544
TI  - Conservation of the Baiji: no simple solution.

PMID- 16909545
TI  - Realities of Baiji conservation.

PMID- 16909546
TI  - "A mission-driven discipline": the growth of conservation biology.
AB  - Conservation biology emerged in the mid-1980s, drawing on established disciplines
      and integrating them in pursuit of a coherent goal: the protection and
      perpetuation of the Earth's biological diversity. Opportunistic in its borrowing
      and application of knowledge, conservation biology had its roots within the
      established biological sciences and resource management disciplines but has
      continually incorporated insights from the empirical experience of resource
      managers, from the social sciences and humanities, and from diverse cultural
      sources. The Society for Conservation Biology (SCB) has represented the field's
      core constituency, while expanding that constituency in keeping with the field's
      integrative spirit. Conservation Biology has served as SCB's flagship
      publication, promoting research, dialog, debate, and application of the field's
      essential concepts. Over the last 20 years the field, SCB, and the journal have
      evolved to meet changing conservation needs, to explore gaps in our knowledge
      base, to incorporate new information from related fields, to build professional
      capacity, and to provide expanded opportunities for international participation.
      In turn, the field, SCB, and journal have prompted change in related fields,
      organizations, and publications. In its dedication to advancing the scientific
      foundations of biodiversity conservation and placing that science at the service
      of society in a world whose variety, wildness, and beauty we care for
      conservation biology represents both a continuation and radical reconfiguration
      of the traditional relationship between science and conservation.

PMID- 16909547
TI  - Who's who in Conservation Biology--an authorship analysis.
AB  - As the flagship journal of the field, Conservation Biology represents a
      multidisciplinary, global constituency of conservation professionals--a
      constituency composed of more than 5200 authors representing 1500 organizations
      and 89 countries. Using bibliometric records of research published in
      Conservation Biology, I evaluated trends in authorship of research papers from
      1987 to 2005. Authorship diversified and became increasingly collaborative over
      time. North Americans now compose one-half of primary authorship, down from 75%
      in the 1990s, and European primary authors contribute a quarter of the journal's
      contributed research. Forty-five countries were represented in volume 19 of the
      journal. The top three most-cited authors are Australian. The percentage of
      single-authored papers declined from 57% in 1987 to 18% in 2005. Collectively,
      academic institutions contribute the most research to Conservation Biology,
      although a government agency, the U.S. Department of Agriculture Forest Service,
      was the single most-productive organization. The maturing of conservation biology
      as a discipline, the complex geographic and multidisciplinary nature of
      conservation questions, and the increased ease of communication in a
      technologically connected world contribute to the increasingly diverse and
      collaborative Conservation Biology authorship.

PMID- 16909548
TI  - Conservation Biology and real-world conservation.
AB  - In the 20 years since Conservation Biology was launched with the aim of
      disseminating scientific knowledge to help conserve biodiversity and the natural
      world, our discipline has hugely influenced the practice of conservation. But we
      have had less impact outside the profession itself and we have not transformed
      that practice into an enterprise large enough to achieve our conservation goals.
      As we look to the next 20 years, we need to become more relevant and important to
      the societies in which we live. To do so, the discipline of conservation biology
      must generate answers even when full scientific knowledge is lacking, structure
      scientific research around polices and debates that influence what we value as
      conservationists, go beyond the certitude of the biological sciences into the
      more contextual debates of the social sciences, engage scientifically with human
      dominated landscapes, and address the question of how conservation can contribute
      to the improvement of human livelihoods and the quality of human life.

PMID- 16909549
TI  - Conservation biology from the perspective of natural resource management
      disciplines.

PMID- 16909550
TI  - Conservation biology: views from the ecological sciences.

PMID- 16909551
TI  - Landscape planning and conservation biology: systems thinking revisited.

PMID- 16909552
TI  - Conservation biology and law: only a start.

PMID- 16909553
TI  - Political science and conservation biology: a dialog of the deaf.

PMID- 16909554
TI  - Common ground between anthropology and conservation biology.

PMID- 16909555
TI  - The economic perspective: conservation against development versus conservation
      for development.

PMID- 16909556
TI  - Translating data into meaning: education in conservation biology.

PMID- 16909557
TI  - Fusion or failure? The future of conservation biology.

PMID- 16909558
TI  - Globally dispersed local challenges in conservation biology.

PMID- 16909559
TI  - Importance of knowledge-intensive economic development to conservation of
      biodiversity in developing countries.

PMID- 16909560
TI  - Using psychology to save biodiversity and human well-being.

PMID- 16909561
TI  - Conservation and climate change: the challenges ahead.

PMID- 16909562
TI  - Agricultural intensification: will land spared from farming be land spared for
      nature?

PMID- 16909563
TI  - Glimpses of conservation biology, act II.

PMID- 16909564
TI  - Conservation science and forest service policy for roadless areas.
AB  - Questions persist regarding whether the science of conservation biology can
      successfully affect environmental decision making. One of the most prominent
      fields of intersection between conservation science and environmental policy is
      public-lands debates in the United States. I reviewed the role of conservation
      science in the roadless-area policies of the U.S. Forest Service. Since 1971, the
      Forest Service has systematically evaluated roadless areas on national forests
      three times, most recently during the Clinton administration's Roadless Area
      Conservation Review (1998-2000) (U.S. Department of Agriculture Forest Service
      2000b). Drawing on the agency's environmental impact statements and supporting
      documents and the internal records of conservation organizations, I examined the
      changing goals, methodology, and outcome of roadless-area advocacy and policy
      Since the 1970s, conservation science has successfully informed public and
      administrative concern for roadless-area protection. Conservation science has
      transformed public discourse regarding roadless areas and has changed the scope
      and rationale of national conservation organizations' goals for roadless-area
      policy from protecting some to protecting all remaining national forest roadless
      areas. The Forest Service has increasingly drawn on the lessons of conservation
      biology to justify its methodology and its administrative recommendations to
      protect roadless areas. The 2000 Roadless Area Conservation Review resulted in a
      recommendation to protect all remaining national forest roadless areas, up from
      22% of roadless areas in the first roadless review. Despite the scientific merits
      of recent roadless-area advocacy and policy, however such initiatives have faced
      political difficulties. The emphasis on large-scale, top-down, national
      approaches to conservation policy has rendered such policies politically
      problematic.

PMID- 16909565
TI  - Transgenics and vertebrate cloning as tools for species conservation.
AB  - It has been suggested that transgenics and vertebrate cloning have a role to play
      in conservation. Now is the time to evaluate their risks and benefits, before
      these technologies are widely implemented in our field. Direct risks of
      transgenics include escape and introgression of transgenes into wild populations;
      weedy invasion by transgenic organisms; toxicity or pathogenicity of engineered
      organisms and their products; and human error in the field testing and tracking
      of transgenic organisms. Indirect risks include environmental effects of
      increased herbicide use; the danger that engineered organisms may aid the
      development of bioweapons; the likelihood that gene patenting will lead to the
      privatization of natural resources; and the diversion of support from less
      glamorous forms of conservation. Formal risk assessments are commonly used to
      evaluate transgenic procedures, but our incomplete understanding of both
      ecosystem processes and the action of transgenes renders most of these
      assessments scientifically and socially unjustified. Nevertheless, a few, low
      risk applications of transgenics may be possible: for example, "super-sterile"
      ornamental cultivars. Vertebrate cloning poses little risk to the environment,
      but it can consume scarce conservation resources, and its chances of success in
      preserving species seem poor To date, the conservation benefits of transgenics
      and vertebrate cloning remain entirely theoretical, but many of the risks are
      known and documented. Conservation biologists should devote their research and
      energies to the established methods of conservation, none of which require
      transgenics or vertebrate cloning.

PMID- 16909566
TI  - The questionable effectiveness of science spending by international conservation
      organizations in the tropics.
AB  - The general context of conservation in the tropics--in the Amazon basin and
      elsewhere--is stagnant or declining funding and rapidly growing threat levels.
      For conservation programs this makes strategic deployment of limited conservation
      resources all the more important. International conservation organizations active
      in the tropics increasingly define themselves as science driven and expend
      considerable resources on science-based activities such as ecoregional analysis,
      field research, and monitoring of ecological variables. l argue that an
      overemphasis on science has generated a series of unintended but serious problems
      for conservation in the tropics. Spending on monitoring and ecoregional analysis
      has effectively starved protection and threat analysis of resources. A decoupling
      of biology from serious cost-benefit analysis has led to the privileging of small
      scale and local analyses, rather than the systemic analyses essential for the
      strategic allocation of scarce conservation resources. Successful conservation in
      the tropics depends on the crossing of biogeography with sophisticated threat
      analysis to identify priority geographies for protection. This should be combined
      with much more systematic engagement with the principal drivers of tropical
      deforestation, especially agribusiness. Caution and a sense of proportion are
      required when balancing the financial demands of science and those of protection.
      I suggest that conservation organizations should cooperate far more in assembling
      and analyzing information on conservation spending and on threat levels and
      biogeography at the continental, national, and regional levels. Site selection
      should follow rather than precede this kind of strategic analysis, and sites
      should be considered elements of a network rather than stand-alone projects. More
      attention should be paid to market-driven conservation through techniques such as
      certification and responsible supply-chain management.

PMID- 16909567
TI  - Designing systematic conservation assessments that promote effective
      implementation: best practice from South Africa.
AB  - Systematic conservation assessment and conservation planning are two distinct
      fields of conservation science often confused as one and the same. Systematic
      conservation assessment is the technical, often computer-based, identification of
      priority areas for conservation. Conservation planning is composed of a
      systematic conservation assessment coupled with processes for development of an
      implementation strategy and stakeholder collaboration. The peer-reviewed
      conservation biology literature abounds with studies analyzing the performance of
      assessments (e.g., area-selection techniques). This information alone, however
      can never deliver effective conservation action; it informs conservation
      planning. Examples of how to translate systematic assessment outputs into
      knowledge and then use them for "doing" conservation are rare. South Africa has
      received generous international and domestic funding for regional conservation
      planning since the mid-1990s. We reviewed eight South African conservation
      planning processes and identified key ingredients of best practice for
      undertaking systematic conservation assessments in a way that facilitates
      implementing conservation action. These key ingredients include the design of
      conservation planning processes, skills for conservation assessment teams,
      collaboration with stakeholders, and interpretation and mainstreaming of products
      (e.g., maps) for stakeholders. Social learning institutions are critical to the
      successful operationalization of assessments within broader conservation planning
      processes and should include not only conservation planners but also diverse
      interest groups, including rural landowners, politicians, and government
      employees.

PMID- 16909568
TI  - Carnivore-livestock conflicts: effects of subsidized predator control and
      economic correlates on the sheep industry.
AB  - Despite the importance of carnivores in terrestrial ecosystems, many nations have
      implemented well-coordinated, state-funded initiatives to remove predators,
      largely because of conflicts with humans over livestock. Although these control
      efforts have been successful in terms of the number of carnivores removed, their
      effects on the viability of the industries they seek to protect are less
      understood. I assessed the efficacy of long-term efforts by the U.S. government
      to improve the viability of the sheep industry by reducing predation losses. I
      used regression analysis and hierarchical partitioning of a 60-year data set to
      explore associations among changes in sheep numbers and factors such as predator
      control effort, market prices, and production costs. In addition, I compared
      trends in the sheep industry in the western United States, where predator control
      is subsidized and coyotes (Canis latrans) are abundant, with trends in eastern
      states that lack federally subsidized predator control and that were (1)
      colonized by coyotes before 1950 or (2) colonized by coyotes between 1950 and
      1990. Although control efforts were positively correlated with fluctuations in
      sheep numbers, production costs and market prices explained most of the model
      variation, with a combined independent contribution of 77%. Trends in sheep
      numbers in eastern and western states were highly correlated (r > or = 0.942)
      independent of the period during which they were colonized by coyotes, indicating
      either that control has been ineffective at reducing predation losses or that
      factors other than predation account for the declines in both regions. These
      results suggest that government-subsidized predator control has failed to prevent
      the decline in the sheep industry and alternative support mechanisms need to be
      developed if the goal is to increase sheep production and not simply to kill
      carnivores.

PMID- 16909569
TI  - Demography, hunting ecology, and pathogen exposure of domestic dogs in the Isoso
      of Bolivia.
AB  - Disease is increasingly recognized as a threat to the conservation of wildlife,
      and in many cases the source of disease outbreaks in wild carnivores is the
      domestic dog. For disease to spill over from a domestic to a wild population,
      three conditions must be satisfied: susceptibility of the wild species, presence
      of the disease agent in the domestic population, and contact between the two
      populations of interest. We investigated the potential for disease spillover from
      the domestic dog population to the wild carnivore population in the Isoso of
      Bolivia, an area of tropical dry forest contiguous with a national park. Using
      questionnaires and discussions with residents, we gathered data on the demography
      of dogs in the Isoso, including adult and neonatal mortality, litter size, and
      hunting frequency. We analyzed a large data set containing self-recorded
      information on hunting in various communities of the Isoso to determine the
      extent of dog participation in hunting and the duration of hunting trips.
      Finally, we took blood samples from dogs in the Isoso for a serosurvey of common
      canine pathogens. More than 95% of dogs had positive titers to canine distemper
      virus and canine parvovirus. There was also a high seroprevalence in dogs for
      other pathogens, a high population turnover of dogs (which may allow diseases to
      be maintained endemically), and frequent opportunities for contact between
      domestic and wild carnivores. Based on our results and the susceptibility of wild
      species previously reported in the literature, domestic dogs represent a disease
      risk for wildlife in the Bolivian Isoso.

PMID- 16909570
TI  - Long-term avifaunal impoverishment in an isolated tropical woodlot.
AB  - Long-term (> 50 years) extinction patterns and processes in isolated tropical
      forest patches are poorly understood. Considering that forest fragments are
      rapidly becoming the common feature of most tropical landscapes, data on the long
      term conservation value of such fragments are urgently needed. We report on
      avifaunal turnover in a tropical woodlot (Bogor Botanical Gardens; 86 ha; 54%
      native and 46% introduced plants; mean 83,649 visitors/month) that has been
      surveyed several times before and after its isolation in 1936. By 2004 the
      original avifaunal richness of this woodlot declined by 59% (97 to 40 species)
      and its forest-dependent avifauna declined by 60% (30 to 12 species). Large
      bodied birds were particularly prone to extinction before 1987, but following
      this time none of the species traits we studied could be considered predictive of
      extinction proneness. All seven forest-dependent bird species that attempted to
      colonize this woodlot by 1987 perished thereafter. Our results show that area
      reduction, isolation, intense human use, and perverse management (e.g.,
      understory removal) of this patch have probably negatively affected the long-term
      sustainability of its forest avifauna.

PMID- 16909571
TI  - Connectivity in an agricultural landscape as reflected by interpond movements of
      a freshwater turtle.
AB  - Connectivity is a measure of how landscape features facilitate movement and thus
      is an important factor in species persistence in a fragmented landscape. The
      scarcity of empirical studies that directly quantify species movement and
      determine subsequent effects on population density have, however, limited the
      utility of connectivity measures in conservation planning. We undertook a 4-year
      study to calculate connectivity based on observed movement rates and movement
      probabilities for five age-sex classes of painted turtles (Chrysemys picta)
      inhabiting a pond complex in an agricultural landscape in northern Virginia
      (U.S.A.). We determined which variables influenced connectivity and the
      relationship between connectivity and subpopulation density. Interpatch distance
      and quality of habitat patches influenced connectivity but characteristics of the
      intervening matrix did not. Adult female turtles were more influenced by the
      habitat quality of recipient ponds than other age-sex classes. The importance of
      connectivity on spatial population dynamics was most apparent during a drought.
      Population density and connectivity were low for one pond in a wet year but
      dramatically increased as other ponds dried. Connectivity is an important
      component of species persistence in a heterogeneous landscape and is strongly
      dependent on the movement behavior of the species. Connectivity may reflect
      active selection or avoidance of particular habitat patches. The influence of
      habitat quality on connectivity has often been ignored, but our findings
      highlight its importance. Conservation planners seeking to incorporate
      connectivity measures into reserve design should not ignore behavior in favor of
      purely structural estimates of connectivity.

PMID- 16909572
TI  - Catastrophic reproductive failure, terrestrial survival, and persistence of the
      marbled salamander.
AB  - Wide variation in reproductive success is common among amphibians that breed in
      seasonal ponds, but persistence of adults can buffer against these fluctuations,
      particularly for long-lived species. We hypothesized that the frequent episodes
      of catastrophic failure of the marbled salamander (Ambystoma opacum) enhance the
      importance of high terrestrial survival. At Rainbow Bay in South Carolina
      reproductive success was poor (< 1 metamorph/breeding female) in nearly half of
      the 22 years that the species bred. Complete failure occurred in 6 of 22 years.
      To study catastrophic failure, we adapted an age-structured, individual-based
      model with density-dependent growth and survival of larvae. The model was based
      on extensive data from local field studies and experiments. With consistently
      good survival in the pond stages, the simulated population required survival
      probabilities in the upland stages (juveniles and adults) near 0.5/year to
      persist and near 0.8/year to achieve the increases observed. Catastrophic
      failure, occurring randomly with probability 0.5/year created additional
      fluctuations in the population, raised the thresholds of survival required for
      persistence, and caused extinction under conditions that were otherwise
      favorable. The marbled salamander at Rainbow Bay is not at great risk of
      extinction because of catastrophic failure, but the risk increases dramatically
      if life span is decreased or frequency of failure is increased. Any reduction in
      terrestrial survival will have deleterious consequences by reducing the breeding
      populations at equilibrium, even if it does not jeopardize persistence. Our model
      provides assessments of risk that can be applied to poorly studied species with
      similar life histories, such as the endangered flatwoods salamander (A.
      cingulatum).

PMID- 16909573
TI  - Effects of the interaction between genetic diversity and UV-B radiation on wood
      frog fitness.
AB  - Genetic diversity may buffer amphibian populations against environmental
      vicissitudes. We hypothesized that wood frogs (Rana sylvatica)from populations
      with lower genetic diversity are more susceptible to ultraviolet-B (UV-B)
      radiation than those from populations with higher diversity. We used RAPD markers
      to obtain genetic diversity estimates for 12 wood frog populations. We reared
      larval wood frogs from these populations and exposed experimental groups of eggs
      and larvae to one of three treatments: unfiltered sunlight, sunlight filtered
      through a UM-B-blocking filter (Mylar), and sunlight filtered through a UV-B
      transmitting filter (acetate). In groups exposed to UVB, larval mortality and
      deformity rates increased significantly, but egg mortality did not. We found a
      significant negative relationship between genetic diversity and egg mortality,
      larval mortality, and deformity rates. Furthermore, the interaction between UV-B
      treatment and genetic diversity significantly affected larval mortality.
      Populations with low genetic diversity experienced higher larval mortality rates
      when exposed to UVB than did populations with high genetic diversity. This is the
      first time an interaction between genetic diversity and an environmental stressor
      has been documented in amphibians. Differences in genetic diversity among
      populations, coupled with environmental stressors, may help explain patterns of
      amphibian decline.

PMID- 16909574
TI  - Conservation benefits of temperate marine protected areas: variation among fish
      species.
AB  - Marine protected areas, and other fishery management systems that impart partial
      or total protection from fishing, are increasingly advocated as an essential
      management tool to ensure the sustainable use of marine resources. Beneficial
      effects for fish species are well documented for tropical and reef systems, but
      the effects of marine protected areas remain largely untested in temperate
      waters. We compared trends in sport-fishing catches of nine fish species in an
      area influenced by a large (500-km2) towed-fishing-gear restriction zone and in
      adjacent areas under conventional fishery management controls. Over the period
      1973-2002 the mean reported weight of above-average-sized (trophy) fish of
      species with early age at maturity and limited home range was greatest within the
      area influenced by the fishing-gear restriction zone. The reported weight of
      trophy fish of species that mature early also declined less and more slowly over
      time within the area influenced by the fishing-gear restriction zone.
      Importantly, the mean reported weight of trophy fish of species that mature late
      and those that undertake extensive spatial movements declined at the same rate in
      all areas. Hence these species are likely to require protected areas > 500 km2
      for effective protection. Our results also indicated that fish species with a
      localized distribution or high site fidelity may require additional protection
      from sport fishing to prevent declines in the number or size of fish within the
      local population.

PMID- 16909575
TI  - Influences of microhabitat constraints and rock-climbing disturbance on cliff
      face vegetation communities.
AB  - Many researchers report that rock climbing has significant negative effects on
      cliff biota. Most work on climbing disturbance, however has not controlled for
      variation in microsite characteristics when comparing areas with and without
      climbing presence. Additionally, some researchers do not identify the style or
      difficulty level of climbing routes sampled or select climbing routes that do not
      represent current trends in the sport. We solved these problems by sampling
      climbing areas used by advanced "sport" climbers and quantifying differences in
      microtopography between climbed and control cliffs. We determined whether
      differences in vegetation existed between pristine and sport-climbed cliff faces
      when microsite factors were not controlled. We then determined the relative
      influence of the presence of climbing, cliff-face microtopography, local physical
      factors, and regional geography on the richness, abundance, and community
      composition of cliff-face vascular plants, bryophytes, and lichens. When we did
      not control for microsite differences among cliffs, our results were consistent
      with the majority of prior work on impacts of climbing (i.e., sport-climbed cliff
      faces supported a lower mean richness of vascular plants and bryophytes and
      significantly different frequencies of individual species when compared with
      pristine cliff faces). When we investigated the relative influences of
      microtopography and climbing disturbance, however the differences in vegetation
      were not related to climbing disturbance but rather to the selection by sport
      climbers of cliff faces with microsite characteristics that support less
      vegetation. Climbed sites had not diverged toward a separate vegetation
      community; instead, they supported a subset of the species found on pristine
      cliff faces. Prior management recommendations to restrict development of new
      climbing routes should be reevaluated based on our results.

PMID- 16909576
TI  - Conservation of species in dynamic landscapes: divergent fates of Silene tatarica
      populations in riparian habitats.
AB  - In transient environments, where local extinctions occur as a result of
      destruction or deterioration of the local habitat, the long-term persistence of a
      species requires successful colonizations at new, suitable sites. This kind of
      habitat tracking should be associated with the asynchronous dynamics of local
      populations, and it can be especially important for the conservation of rare
      plant species in riparian habitats. We determined spatiotemporal variation in the
      demography of the perennial Silene tatarica (L.) Pers. in 15 populations (1998
      2003) located in periodically disturbed riparian habitats. The habitats differed
      according to their morphology (flat shores, slopes) and the amount of bare ground
      (open, intermediate, closed) along a successional gradient. We used elasticity
      and life-table response analyses and stochastic simulations to study the
      variation in population demography. Finite population growth rate was higher in
      intermediate habitats than in open and closed habitats. In stochastic simulations
      population size increased in most cases, but four populations were projected to
      become extinct within 12-70 years. The viability of local populations depended
      most on the survival and growth of juvenile individuals and on the fecundity of
      large fertile individuals. On a regional scale, the persistence of this species
      will require a viable network of local populations as protection against local
      extinctions caused by natural disturbances and succession. Accordingly, the long
      term persistence of riparian species may depend on habitat changes; thus, their
      conservation requires maintenance of natural disturbance dynamics. Along
      regulated rivers, management activities such as the creation of open habitats for
      new colonization should be implemented. Similarly, these activities can be rather
      general requirements for the conservation of endangered species dependent on
      transient habitats along successional gradients.

PMID- 16909577
TI  - Effects of the surrounding matrix on tree recruitment in Amazonian forest
      fragments.
AB  - Little is known about how the surrounding modified matrix affects tree
      recruitment in fragmented forests. We contrasted effects of two different matrix
      types, Vismia- and Cecropia-dominated regrowth, on recruitment of pioneer tree
      species in forest fragments in central Amazonia. Our analyses were based on 22, 1
      ha plots in seven experimental forest fragments ranging in size from 1 to 100 ha.
      By 13 to 17 years after fragmentation, the population density of pioneer trees
      was significantly higher in plots surrounded by Vismia regrowth than in plots
      surrounded by Cecropia regrowth, and the species composition and dominance of
      pioneers differed markedly between the two matrix types. Cecropia sciadophylla
      was the most abundant pioneer in fragments surrounded by Cecropia regrowth
      (constituting nearly 50% of all pioneer trees), whereas densities of species in
      Vismia-surrounded fragments were distributed more evenly. Thus the surrounding
      matrix had a strong influence on patterns of tree recruitment in Amazonian forest
      fragments.

PMID- 16909578
TI  - Applying network analysis to the conservation of habitat trees in urban
      environments: a case study from Brisbane, Australia.
AB  - In Australia more than 300 vertebrates, including 43 insectivorous bat species,
      depend on hollows in habitat trees for shelter with many species using a network
      of multiple trees as roosts. We used roost-switching data on white-striped
      freetail bats (Tadarida australis; Microchiroptera: Molossidae) to construct a
      network representation of day roosts in suburban Brisbane, Australia. Bats were
      caught from a communal roost tree with a roosting group of several hundred
      individuals and released with transmitters. Each roost used by the bats
      represented a node in the network, and the movements of bats between roosts
      formed the links between nodes. Despite differences in gender and reproductive
      stages, the bats exhibited the same behavior throughout three radiotelemetry
      periods and over 500 bat days of radio tracking: each roosted in separate roosts,
      switched roosts very infrequently, and associated with other bats only at the
      communal roost. This network resembled a scale-free network in which the
      distribution of the number of links from each roost followed a power law. Despite
      being spread over a large geographic area (> 200 km2), each roost was connected
      to others by less than three links. One roost (the hub or communal roost) defined
      the architecture of the network because it had the most links. That the network
      showed scale-free properties has profound implications for the management of the
      habitat trees of this roosting group. Scale-free networks provide high tolerance
      against stochastic events such as random roost removals but are susceptible to
      the selective removal of hub nodes. Network analysis is a useful tool for
      understanding the structural organization of habitat tree usage and allows the
      informed judgment of the relative importance of individual trees and hence the
      derivation of appropriate management decisions. Conservation planners and
      managers should emphasize the differential importance of habitat trees and think
      of them as being analogous to vital service centers in human societies.

PMID- 16909579
TI  - Objectives for multiple-species conservation planning.
AB  - The first step in conservation planning is to identify objectives. Most stated
      objectives for conservation, such as to maximize biodiversity outcomes, are too
      vague to be useful within a decision-making framework. One way to clarify the
      issue is to define objectives in terms of the risk of extinction for multiple
      species. Although the assessment of extinction risk for single species is common,
      few researchers have formulated an objective function that combines the
      extinction risks of multiple species. We sought to translate the broad goal of
      maximizing the viability of species into explicit objectives for use in a
      decision-theoretic approach to conservation planning. We formulated several
      objective functions based on extinction risk across many species and illustrated
      the differences between these objectives with simple examples. Each objective
      function was the mathematical representation of an approach to conservation and
      emphasized different levels of threat. Our objectives included minimizing the
      joint probability of one or more extinctions, minimizing the expected number of
      extinctions, and minimizing the increase in risk of extinction from the best-case
      scenario. With objective functions based on joint probabilities of extinction
      across species, any correlations in extinction probabilities had to be known or
      the resultant decisions were potentially misleading. Additive objectives, such as
      the expected number of extinctions, did not produce the same anomalies. We
      demonstrated that the choice of objective function is central to the decision
      making process because alternative objective functions can lead to a different
      ranking of management options. Therefore, decision makers need to think carefully
      in selecting and defining their conservation goals.

PMID- 16909580
TI  - Detecting population declines over large areas with presence-absence, time-to
      encounter, and count survey methods.
AB  - Ecologists often discount presence-absence surveys as a poor way to gain insight
      into population dynamics, in part because these surveys are not amenable to many
      standard statistical tests. Still, presence-absence surveys are sometimes the
      only feasible alternative for monitoring large areas when funds are limited,
      especially for sparse or difficult-to-detect species. I undertook a detailed
      simulation study to compare the power of presence-absence, count, and time-to
      encounter surveys to detect regional declines in a population. I used a modeling
      approach that simulates both population numbers and the monitoring process,
      accounting for observation and other measurement errors. In gauging the efficacy
      of presence-absence surveys versus other approaches, I varied the number of
      survey sites, the spatial variation in encounter rate, the mean encounter rate,
      and the type of population loss. My results showed that presence-absence data can
      be as or more powerful than count data in many cases. Quantitative guidelines for
      choosing between presence-absence surveys and count surveys depend on the
      biological and logistical constraints governing a conservation monitoring
      situation. Generally, presence-absence surveys work best when there is little
      variability in abundance among the survey sites, the organism is rare, and the
      species is difficult to detect so that the time spent getting to each survey site
      is less than or equal to the time spent surveying each site. Count surveys work
      best otherwise. I present a case study with count data on the Northern Flicker
      (Colaptes auratus) from the North American Breeding Bird Survey to illustrate how
      the method might be used with field-survey data. The case study demonstrates that
      a count survey would be the most cost-effective design but would entail reduction
      in the number of sites. If this site reduction is not desirable, a presence
      absence survey would be the most cost-effective survey.

PMID- 16909581
TI  - Accounting for management costs in sensitivity analyses of matrix population
      models.
AB  - Traditional sensitivity and elasticity analyses of matrix population models have
      been used to inform management decisions, but they ignore the economic costs of
      manipulating vital rates. For example, the growth rate of a population is often
      most sensitive to changes in adult survival rate, but this does not mean that
      increasing that rate is the best option for managing the population because it
      may be much more expensive than other options. To explore how managers should
      optimize their manipulation of vital rates, we incorporated the cost of changing
      those rates into matrix population models. We derived analytic expressions for
      locations in parameter space where managers should shift between management of
      fecundity and survival, for the balance between fecundity and survival management
      at those boundaries, and for the allocation of management resources to sustain
      that optimal balance. For simple matrices, the optimal budget allocation can
      often be expressed as simple functions of vital rates and the relative costs of
      changing them. We applied our method to management of the Helmeted Honeyeater
      (Lichenostomus melanops cassidix; an endangered Australian bird) and the koala
      (Phascolarctos cinereus) as examples. Our method showed that cost-efficient
      management of the Helmeted Honeyeater should focus on increasing fecundity via
      nest protection, whereas optimal koala management should focus on manipulating
      both fecundity and survival simultaneously. These findings are contrary to the
      cost-negligent recommendations of elasticity analysis, which would suggest
      focusing on managing survival in both cases. A further investigation of Helmeted
      Honeyeater management options, based on an individual-based model incorporating
      density dependence, spatial structure, and environmental stochasticity, confirmed
      that fecundity management was the most cost-effective strategy. Our results
      demonstrate that decisions that ignore economic factors will reduce management
      efficiency.

PMID- 16909582
TI  - Population growth, human development, and deforestation in biodiversity hotspots.
AB  - Human population and development activities affect the rate of deforestation in
      biodiversity hotspots. We quantified the effect of human population growth and
      development on rates of deforestation and analyzed the relationship between these
      causal factors in the 1980s and 1990s. We compared the averages of population
      growth, human development index (HDI, which measures income, health, and
      education), and deforestation rate and computed correlations among these
      variables for countries that contain biodiversity hotspots. When population
      growth was high and HDI was low there was a high rate of deforestation, but when
      HDI was high, rate of deforestation was low, despite high population growth. The
      correlation among variables was significant for the 1990s but not for the 1980s.
      The relationship between population growth and HDI had a regional pattern that
      reflected the historical process of development. Based on the changes in HDI and
      deforestation rate over time, we identified two drivers of deforestation: policy
      choice and human-development constraints. Policy choices that disregard
      conservation may cause the loss of forests even in countries that are relatively
      developed. Lack of development in other countries, on the other hand, may
      increase the pressure on forests to meet the basic needs of the human population.
      Deforestation resulting from policy choices may be easier to fix than
      deforestation arising from human development constraints. To prevent
      deforestation in the countries that have such constraints, transfer of material
      and intellectual resources from developed countries may be needed. Popular
      interest in sustainable development in developed countries can facilitate the
      transfer of these resources.

PMID- 16909583
TI  - Effects of warming conditions in eastern North American forests on red-backed
      salamander morphology.
AB  - Several studies have reported climate-associated changes in phenotypically
      plastic traits of amphibians, yet it remains unknown whether amphibians can
      manifest an evolutionary response to global climate change at the rate and
      magnitude that it is occurring. To assess this issue, we examined temporal change
      in the morphology of the red-backed salamander (Plethodon cinereus), a small,
      abundant woodland salamander distributed widely in eastern North America with two
      distinct morphotypes: striped individuals associated with cooler microclimates
      and unstriped individuals associated with warmer microclimates. We compiled morph
      frequencies for 50,960 individual salamanders from 558 sites as recorded in the
      published literature and in unpublished field notes of herpetologists between
      1908 and 2004. We observed that striping probability increased with increasing
      latitude, longitude, and elevation and decreased (from 80% to 74% range wide)
      with time. The combined forces of regional climate warming and, particularly,
      forest disturbance have evidently been sufficient to cause morphological
      evolution in this amphibian over the last century.

PMID- 16909584
TI  - Cerulean Paradise-Flycatcher not extinct: subject of the first cover lives.

PMID- 16909585
TI  - The CEO workout.

PMID- 16909586
TI  - Warren Buffett gives it away.

PMID- 16909588
TI  - [Construction of pORF-mIG and activity evaluation of MIG in vitro].
AB  - OBJECTIVE: To establish a transformant of monokine induced by interferon-gamma
      (MIG) with the eukaryotic expression vector for further investigating the
      efficacy of its use in antitumor gene therapy. METHODS: The MIG full-length cDNA
      was amplified from pBLAST-MIG and was cloned into the eukaryote expression vector
      pORF-mcs, and the resulted recombinant plasmid was named pORF-MIG. The
      recombinant pORF-MIG was determined with restriction enzyme and sequencing, and
      then it was transfected into COS-7 cells by Lipfectamin. Expression of the
      transformant was detected by immunoblot assay, and the bioactivity was assessed
      by chemotaxis assay. RESULTS: The restriction analysis and the sequence
      determination confirmed that the recombinant pORF-MIG contained the MIG full
      length cDNA. And the transformants of pORF-MIG expressed the MIG protein which
      could apparently attract the activated lymphocytes. CONCLUSION: The recombinant
      pORF-MIG was constructed successfully, and this recombinant eukaryotic expression
      vector could be used in additional studies on the biological effect of MIG and
      its use in anti-tumor gene therapy.

PMID- 16909587
TI  - [Study on cloning of hTERT promoter and its targeting transcriptional activities
      in telomerase-positive lung cancer cells].
AB  - OBJECTIVE: To clone sequence of hTERT promoter and study its transcriptional
      activity and its relationship with hTERT mRNA expression and telomerase activity
      in various kinds of human lung cancer cells and normal cells, and to investigate
      the targeting transcriptional activity of hTERT promoter in tumor cells. METHODS:
      About 1.1 kb promoter of the 5'flanking sequence of the hTERT was amplified from
      genomic DNA isolated from 293 cells by polymerase chain reaction (PCR). After
      being confirmed by DNA sequencing, the hTERT promoter was inserted into
      luciferase reporter vectors (pGL3-basic) to reconstruct a recombinant named pGL3
      hTERTp. Then pGL3-hTERTp was transiently transfected into lung cancer cell A549,
      SPC-A-1, LTEPa-2, NCI-H446, YTMLC-9, GLC-82, 95D, A2, and normal cell of MRC-5.
      The transcriptional activities of hTERT promoter in various cells were determined
      by measuring the luciferase activities. hTERT mRNA expression and telomerase
      activity were determined by RT-PCR and TRAP ELISA. RESULTS: Eelectrophoresis
      demonstrated that the hTERT promoter amplified by PCR was about 1.1 kb long, and
      DNA sequencing showed a sequence the same as the hTERT promoter registered in
      GenBank being 1084 bp in length. The recombinant of plasmid pGL3-hTERTp was
      confirmed by double digestion and PCR methods with correct results. hTERT mRNA
      and telomerase activity were expressed in all of eight lung cancer cell lines at
      varied levels, but not expressed in normal cell. Transient transfection assay and
      Luciferase assay also revealed that hTERT promoter had different transcriptional
      activities in various lung cancer cells, but no transcriptional activity was
      shown in normal cells. CONCLUSION: 1084 bp hTERT promoter cloned has specific
      transcriptional activities in various telomerase-positive lung cancer cells, and
      it may act as control element in tumor-targeting gene therapy.

PMID- 16909589
TI  - [Expression and characterization of mouse 17-1A antigen from Pichia pastoris].
AB  - OBJECTIVE: This is a ground work in preparation for the development of a vaccine
      against tumor, in which 17-1A glucoprotein, a tumor associated antigen (TAA), was
      cloned and expressed in Pichia pastoris. METHODS: The cDNA of 17-1A gene was
      cloned from nephridial tissue of mouse embryo by RT-PCR and subsequently inserted
      into pPICZaA plasmid after digestion with Xho I and Xba I. The linearized
      recombinant plasmid was transformed into Pichia pastoris strain GS115. 17-1A
      glucoproteins were secreted into culture supernatant through alpha-signal peptide
      of AOX I after inducation with methanol. The protein products were analyzed and
      characterized by SDS-PAGE and Western-blot. RESULTS: The plasmid pPICZalphaA-17
      1A was constructed and verified by sequenceing. 17-1A glucoproteins were
      expressed stably and glycosylated in Pichia pastoris. CONCLUSION: Glycosylated
      tumor associated antigen 17-1A can be expressed in Pichia pastoris.

PMID- 16909590
TI  - [Construction of the recombinant adenovirus vector with EGFR antisense cDNA of
      controlling cell cycle].
AB  - OBJECTIVE: To recombine the adenovirus vector carrying EGFR sence/antisense cDNA
      which takes part in control of cell cycle. METHODS: The 1032 bp EGFR
      sence/antisense cDNA fragment was cloned into the shuttle plasmid pAdTrack-CMV.
      The resultant plasmid and the backbone plasmid pAdEasy-1 were transferred into E.
      coli BJ5183 for homologous recombination, and the recombinant adenoviruses were
      generated in cells. The recombinant adenoviruses were packaged and amplified in
      the 293 cells. Then the viral titer was detected by GFP. RESULTS: The recombinant
      adenovirus vector carrying EGFR sence/antisense cDNA to control the cell cycle
      was constructed successfully. The viral titers were 2.2 x 10(9) efu/mL and 2.5 X
      10(9) efu/mL respectively. CONCLUSION: The recombinant adenovirus vector
      constructed by us could introduce EGFR antisense cDNA into the laryngeal squamous
      cell carcinoma line or tumor tissue, which would provide an experiment basis to
      study further the interfered mechanism of signal transdution and the therapies of
      laryngeal squamous cell carcinoma.

PMID- 16909591
TI  - [Study in vitro on p16beta interfering the cell cycle signal conduction of
      laryngeal squamous cell carcinoma].
AB  - OBJECTIVE: To investigate the effect of p16beta interfering with the signal
      conduction of Hep-2 cell cycle in Vitro. METHODS: AdEasy Vector System was used
      to construct the recombinant adenovirus vector AdEasy-GFP-p1613. The recombinant
      adenovirus vector could introduce p16beta gene into HEK 293 cell. Then the
      purified recombinant adenovirus was used to infect Hep-2 cells in vitro. The
      protein expression of p16beta, proliferation inhibition, cell cycle arrest, DNA
      content, apoptosis ratio in Hep-2 cells were examined by MTT, Western blotting
      analysis, Flow cytometry assay, Immunocytochemistry respectively. RESULTS: The
      recombinant adenovirus Adeasy-p16beta was constructed successfully and higher
      titer recombinant adenovirus particle was got. When Adeasy-p16beta was
      transferred into Hep-2 cells, both the growth inhibition and P14 (ARF) protein
      overexpression in Hep-2 cells were visible effectively. The most Hep-2 cells were
      blocked in G1/G0 phase and the cell apoptosis ratio increased. CONCLUSION: The
      p16beta in Hep-2 cell infected by recombinant adenovirus, which lead to express
      P14 (ARF) protein effectively and to inhibit cell proliferative activation,
      effectively interfere the signal conduction mechanisms of culture Hep-2 laryngeal
      squamous cell carcinoma, and the growth of much cultured cells is blocked in
      G1/G0 phase.

PMID- 16909592
TI  - [The experiment study on RNAi inhibiting the expression of survivin and inducing
      the apoptosis of pancreatic cancer cells].
AB  - OBJECTIVE: To investigate the inhibitory effects of RNAi expression vector
      suppressing the expression of survivin and inducing the apoptosis of pancreatic
      cancer cell PANC-1. METHODS: The expression of survivin was examined with RT-PCR
      and immunofluorescence protocols. The survivin gene was cloned into the T-vector
      and sequenced, at the same time, the RNAi expression vectors aimed survivin were
      successfully constructed, and then transfected into PANC-1 cells with liposomes.
      The expression of survivin mRNA was detected with RT-PCR and Western-blot
      techniques. The rate of cell apoptosis was measured with FACS. RESULTS: There was
      a high degree expression of survivin in PANC-1 cells. The DNA sequence was
      according with the survivin gene in GENE BANK. The survivin expression was
      inhibited about 70% by pTZU6 + 1-svv2 RNAi expression vectors, and the apoptosis
      cells increased. CONCLUSION: The RNAi expression vector can effectively inhibit
      the survivin expression and induce the apoptosis in PANC-1 cells.

PMID- 16909593
TI  - [Recombinant adenovirus vectors carrying antisense matrix metalloproteinase-2
      inhibits hepatocellular carcinoma growth in vivo].
AB  - OBJECTIVE: To investigate the inhibitory effect of a recombinant adenoviral
      vector carrying antisense matrix metalloproteinase-2(MMP2) on the growth of
      hepatocellular carcinoma(HCC) in vivo. METHODS: The recombinant adenoviral vector
      carrying antisense MMP2(Ad-MMP2(AS))which had been constructed by us in readiness
      was used to infect the human HCC cell line (Bel-7402). Then the invasiveness of
      the Bel-7402 cells was assayed in Matrigel, and the production of MMP2 in the Bel
      7402 cells was detected with Western blot analysis and Gelatin zymography. After
      the Ad-MMP2(AS)-infected Bel-7402 cells being subcutaneously inoculated in nude
      mice, the production of tumors was under observation, and then Ad-MMP2(AS) was
      injected intratumorally into the pre-existing tumors. RESULTS: Compared with PBS
      or Ad-CMV-infected cells, infection of Bel-7402 cells with Ad-MMP2(AS)
      significantly reduced MMP2 enzyme activity, the invasiveness resulted in 52%
      reduction in Matrigel assays, and the tumor volume displayed a 4.3-fold reduction
      in nude mice. In addition, direct intratumoral injection of Ad-MMP2(AS) into pre
      existing tumors significantly impaired the further expansion of the tumor mass
      and resulted in a 63% reduction in tumor cell growth. CONCLUSION: The recombinant
      adenovirus with antisense MMP2 can effectively inhibit the invasiveness and
      growth of Bel-7402 cells in vitro and in vivo, and has a therapeutic potential
      for HCC.

PMID- 16909594
TI  - [Effects of intra-amygdaloid injection of motilin on the interdigestive migrating
      myoelectrical complex in rat].
AB  - OBJECTIVE: This study is undertaken to explore the effects of motilin in the
      amygdaloid nucleus on the interdigestive migrating myoelectrical complex (MMC) in
      rats. METHODS: Adult SD rats of either sex were used. 0.5 microL motilin (0.74
      nmol/microL) was injected into the guide cannula which had been stereotaxically
      implanted into the amygdaloid nucleus. Then the MMC was recorded by an RM6240B
      multilead physiological recording system. Some rats also received
      subdiaphragmatic vagotomy, or intravenous injection of the M-cholinergic receptor
      antagonist atropine (50 microg/kg), the alpha-adrenergic receptor antagonist
      phentolamine (200 microg/kg), the beta-adrenergic receptor antagonist propranolol
      (100 microg/kg), the anti-motilin serum. RESULTS: After motilin was injected into
      the amygdaloid nucleus, the duodenal MMC cycle duration was decreased
      significantly, (586.3 +/- 42.0) vs. (694.0 +/- 36.2)s. However, the amplitude of
      phase III and the frequency of phase III was increased, (294.7 +/- 43.2) vs
      (255.1 +/- 23.5) microV and (23.1 +/- 0.6) vs. (18.2 +/- 0.4) bursts/min. But
      there were no effects on the duration of phase III. The percentage change in
      frequency of phase III was much greater than the percentage change in amplitude
      of phase III, (54.3 +/- 5.6) vs. (22.4 +/- 4.3). The effects of motilin in the
      amygdaloid nucleus on MMC were completely abolished by subdiaphragmatic vagotomy.
      The effects of motilin in the amygdaloid nucleus on MMC were not affected by
      intravenously injected atropine, phentolamine or propranolol. The anti-motilin
      serum partly abolished the effects of motilin in the amygdaloid nucleus on MMC.
      CONCLUSION: Motilin in the amygdaloid nucleus has effects on the duodenal MMC
      cycle duration, the amplitude of phase III and the frequency of phase III, all of
      which may rely on either the effects of noncholinergic and nonadrenergic neurons
      on duodenal smooth muscle, or the increase of local motilin via nucleus amygdalae
      hypothalamus-brain stem-vagus pathway.

PMID- 16909595
TI  - [Combined low-dose chemotherapy inhibiting angiogenesis and growth of Lewis lung
      cancinoma xenografts in mice].
AB  - OBJECTIVE: To investigate the antiangiogenic and antitumor effects of combined
      low-dose cyclophosphamide(CTX) and paclitaxel(PTX). METHODS: In this experiment,
      Lewis lung carcinoma model was established in C57BIL6 mice. Forty mice were
      randomly divided into four groups: control group, cyclophosphamide (170 mg/kg,
      q6d) group, paclitaxel (10 mg/kg, q7d) group, and cyclophosphamide plus
      paclitaxel group. The growth of tumor and the sideeffect of each therapy were
      investigated. Microvessel density (MVD) was assessed by CD31 immunostaining, and
      immunohistochemistry (IHC) image analysis was performed for semiquantification of
      vascular enthothelial growth factor (VEGF). RESULTS: The combined low-dose
      therapy with cyclophosphamide and paclitaxel was most effective for antagonizing
      tumor-associated angiogensis; the mice of this group had the lowest MVD and VEGF
      expression, compared to mice of other groups (P < 0.005). The combination therapy
      also brought about higher antitumor rate, lower tumor volume, and lower tumor
      weight than did the single therapy (P < 0.005). Paclitaxel (10 mg/kg, q7d)
      therapy had the slightest side-effects; other therapies had similar acceptable
      side effects. CONCLUSION: The combined use of low dose cyclophosphamide and
      paclitaxel has synergistic antiangiogenic effect on the mouse model of Lewis lung
      carcinoma; the combination of these two agents is clearly more effective for
      inhibiting angiogenesis and growth of tumor.

PMID- 16909596
TI  - [Mechanism of receptor for retinoids inducing apoptosis of human melanoma cell
      line A375].
AB  - OBJECTIVE: To investigate the mechanism of receptors for retinoids inducing
      apoptosis of human melanoma cell line A375. METHODS: The effects of 3 kinds of
      retinoids (9-cis-RA, at-RA and 13-cis-RA), of TTNPB (RAR agonist) and of
      Methoprene acid (Ma, RXR agonist) on apoptosis of A375 cells were studied by
      detecting the expression of Bcl-2/Bax and by using. Annexin V/PI staining
      analysis, TUNEL detection and active Caspase-3 analysis. RESULTS: Retinoids and
      TTNPB could up-regulate the expression of Bax and down-regulate the expression of
      Bcl-2. The results of TUNEL and Annexin V/PI staining analysis showed that all of
      retinoids and TTNPB could induce apoptosis of A375 cells, compared with control
      group (P < 0.05); the effect of TTNPB was significantly greater than that of
      others (P < 0.05), but Ma was similar to the control (P > 0.05). Active Caspase-3
      analysis showed that TTNPB and all of retinoids could up-regulate the expression
      of Caspase-3, and the effect of TTNPB was significantly greater than that of
      others (P < 0.05). CONCLUSION: Caspase-3 pathway is involved in the process for
      retinoids inducing apoptosis of A375 cells. The activation of RAR may have
      relation with retinoids inducing apoptosis of A375 cells, but may have no longer
      relation with RXR.

PMID- 16909597
TI  - [Comparative study of that synergistic effect of cisplatin combined with compound
      herbal medicinal prescription for tonic quality and activating blood circulation
      is on SKOV3 cell proliferation and apoptosis].
AB  - OBJECTIVE: To investigate the synergistic effects on cell apoptosis and growing
      restriction of SKOV3 cells by the combination of compound herbal medicinal
      prescription (CHMP) with cisplatin (DDP). METHODS: Cisplatin and two CHMP for
      tonic quality(CHMP1) and activating blood circulation (CHMP2), which was
      medicated serum, were prepared and used to treat the human ovarian carcinoma cell
      line SKOV3. By serum pharmacologic method, the growth and apoptosis of SKOV3 cell
      were observed at different time points(24,48,72, 96 h) with different
      concentrations of medicated serum. Coefficient of drug interaction (CDI) between
      CHMP, and CHMP2 was studied by MTT method. The effects of control group(A
      group),CHMP1 group(B group),CHMP2 group (C group), DDP group(D group), CHMP1 +
      DDP group(E group), CHMP2 + DDP group(Fgroup)to SKOV3 cell were studied by flow
      cytometry; and the cell apoptosis was observed by agarose electrophoresis; the
      expressions of TNFR1, caspase-8 on each group were analyzed by Western blot
      method. RESULTS: Synergistic effects were found between herbal medicinal mixtures
      and DDP, Restraining rate of SKOV3 and CHMP serum concentration was not in a dose
      dependent manner as DDP was. CDI between CHMPI and CHMPS was found to be
      significant difference (CDI of CHMP1, CHMP2 and DDPwas 0.66, 0.58 respectively).
      It showed that the combined treatment was able to get better effect than single
      drug treatment. The performed agarose electrophoresis revealed the extracted DNA
      to show a typical ladder patterns for cell apoptosis. The analysis results of
      western blot showed the increased expressions of TNFR1 and caspase-8 after
      combined using of medicine, which were accord to the rates of apoptosis.
      CONCLUSIONS: CHMP drug granules show the synergistic effects with DDP, and the
      suppressing functions in the course of cell proliferation, and the inducing
      effect on apoptosis of human ovarian carcinoma cell line SKOV3 in vitro. And this
      mechanism is showed to be sponsored by the activation of TNFR1 and Caspase-8.

PMID- 16909598
TI  - [Effects of selective and non-selective cyclooxygenase-2 inhibitor on the growth
      of colon cancer cells].
AB  - OBJECTIVE: To evaluate the effects of selective and non-selective cyclooxygenase
      2 on the growth and apoptosis of colon cancer cell lines in vitro. METHODS: The
      proliferation of colon cancer cells was determined by MTT assay, and the cell
      cycle progression was analyzed by flow cytometric assay. Annexin V/PI staining in
      combination with flow cytometric assay was used to detect apoptosis induced by
      NSAIDs. RESULTS: It was found that celecoxib, meloxicam and aspirin could inhibit
      the growth of HT-29 or SW480 cell and showed a concentration dependent pattern.
      COX-2 protein was expressed in HT-29 and LS174-T, but not in SW480 cells. In
      addition, PCNA levels in both HT-29 cell and SW480 cells were reduced by aspirin
      and celecoxib. Both aspirin (10 mmol/ L) and celecoxib (50 micromol/L) induced
      apoptosis of HT-29 and SW480 colon cancer cells, the apoptosis rates were 4.8%,
      17.7% and 5.1%, 20.4% respectively. CONCLUSION: Both COX-2 selective and non
      selective inhibitors can potentially inhibit the growth of colon cell lines and
      such inhibitory effect on COX-2 negative colon cancer cells is also evident.

PMID- 16909599
TI  - [Association between polymorphisms of CYP17 and CYP3A4 genes and intrahepatic
      cholestasis of pregnancy in Chengdu].
AB  - OBJECTIVE: investigate whether polymorphisms in estrogen-metabolizing genes,
      CYP17 and CYP3A4, are associated with intrahepatic cholestasis of pregnancy (ICP)
      in Chengdu China. METHODS: The -1931T/C polymorphism in the 5'-untranslated
      region of CYP17 gene and the -290A/G polymorphism in the 5'-regulatory region of
      CYP3A4 gene were detected by polymerase chain reaction-restriction fragment
      length polymorphism (PCR-RFLP) method in 100 pregnant women with ICP (ICP group)
      and 100 normal pregnant women (control group) in Chengdu. RESULTS: The T/C
      polymorphism of the CYP17 gene was shown clearly in ICP and control groups, but
      the genotype distributions (TT, TC and CC) and allele frequencies (T and C) of
      CYP17 polymorphism were of no significant difference between the two groups (P >
      0.05). No CYP3A4-V (CTP3A4 * 1B) allele was found in the 200 individuals studied.
      The genotype of CYP3A4 was wt/wt in all the pregnant women. CONCLUSION: The T/C
      polymorphism of CYP17 gene is not associated with the risk of ICP in Chengdu.
      There are not -290A/G polymorphism of CYP3A4 gene among pregnunt women in
      Chengdu.

PMID- 16909600
TI  - [Clinical features and CD38 polymorphisms of latent autoimmune diabetes of adults
      (LADA) in Chengdu].
AB  - OBJECTIVE: To find out the clinical characteristic elements as parameters and
      detect the polymorphism at PvU II endonuclease site and Arg(140) Trp mutation of
      the CD38 gene of LADA patients in the Chengdu area. METHODS: The clinical
      parameters, islet cell-specific autoantibodies, C-peptide levels, genetic and
      mutation frequency of the CD38 gene in 44 patients with LADA and 67 patients with
      T2DM were investigated and compared with those in 25 normal controls. RESULTS:
      The patients of 30-50 years of age had higher prevalence of LADA. A number of
      LADA patients were obese or over-obese. The positivity of GAD-Ab, ICA and IAA
      declined with the increase of age. Both LADA and T2DM patients had the
      polymorphisms of B/B and A/B of the CD38 gene, but the healthy controls did not
      have such polymorphisms. Arg1140 Trp mutation was not found in both patients and
      healthy controls. CONCLUSION: This research revealed no relationship between the
      on-set of LADA and the CD38 polymorphism and CD38 Arg(140) Trp mutation.

PMID- 16909601
TI  - [Analysis of loss of heterozygosity induced by vinblastine at tk locus in human
      lymphoblastoid cell line TK6].
AB  - OBJECTIVE: To establish TK gene mutation assay using human lymphoblastoid cell
      line TK6 and to study the genotoxic mechanism of Vinblastine (VBL). METHODS: TK6
      cells were treated with Vinblastine at different concentrations (0.625 ng/mL,
      1.250 ng/mL, 2.500 ng/mL and 5.000 ng/mL)for 24 h and TK gene mutation assay were
      experimented. Relative survival (RS%), relative suspension growth (RSG%),
      mutation frequency at tk locus and percentages of slow growth mutant (SC%) were
      detected and loss of heterozygosity (LOH) of mutants were analyzed. RESULTS: A
      decreased RS% and RSG% and an increased mutation frequency at tk locus were
      observed in a dose-dependent manner when the TK6 cells were treated with 0.625,
      1.250, 2.500 and 5.000 ng/mL of Vinblastine respectively for 24 h. The result
      demenstrated that about 96.4% of Vinblastine-induced mutants were LOH. Among
      them, 39.3% were hemi-LOH and 57.1% were homo-LOH respectively. CONCLUSION: TK6
      cell line can be used to detect the genotoxicity of Vinblastine and LOH was the
      major mutation events in Vinblastine-induced mutants.

PMID- 16909602
TI  - [The effects of flutamide on the full gene expression of early testis development
      of embryonic period male SD].
AB  - OBJECTIVE: To study the effects of Flutamide (Flu) on the full gene expression of
      early testis development of embryonic period in male SD rats. METHODS: Flu was
      injected subcutaneously (sc) with NS at doses of 6.25 mg/kg x d from 12th to 17th
      gestation days (GD), and in control group with tales doses NS. Fifty pregnant SD
      rats were sacrificed on GD 20. The mRNA were extracted respectively from fetus
      testis with treated and untreated Flu, then transcribed reversely to cDNA and
      labeled with cy5 and cy3 fluorescence. Subsequently, cDNA probes were hybridized
      to the Mouse40S cDNA microarray and fluorescence signals were analyzed.
      Meanwhile, we took out of the right testes of male offspring to make the
      detection of immunohistochemistry (IHC). Furthermore, we determined the level of
      testosterone by enzyme-linked immunosorbentassay (ELISA). RESULTS: Compared with
      the control group, a total of 31 identified genes expressed differently,
      including 14 down-regulated and 17 upregulated genes. However, the function of 5
      down-regulated and 10 upregulated difference expression genes are unknown in
      Genbank. This finding has provided important reference basis for the molecular
      mechanism of reproductive development of Flu in the future. The activity of two
      important enzymes was cut down by IHC. The level of testosterone was decreased by
      ELISA. CONCLUSION: The results indicated that Flu administrated to F0 pregnant
      rats can damage apparently to the reproductive development of embryonic period
      male SD rats in many ways, and can cause the abnormality of sexual
      differentiation and sexual development in rats.

PMID- 16909603
TI  - [Reproductive toxicity of formaldehyde to adult male rats and the functional
      mechanism concerned].
AB  - OBJECTIVE: To assess the reproductive toxicity exerted by formaldehyde to adult
      male rats and the functional mechanism therein in volved. METHODS: Forty adult
      male rats were randomLy divided into 4 groups. One group served as control. The
      other 3 groups as exposure groups were intraperitoneally injected with
      formaldehyde at the dose of 0.10 mg/kg x d, 1.00 mg/kg x d, 10 mg/kg x d
      respectively and continuously for 14 days. The weight and morphology of testis,
      the quality and amount of sperm, and the serum hormone were examined. In
      addition, the apoptosis rate of testis tissue was examined by TUNEL and the
      expression of Fas gene in testis tissue by immunohistochemistry. RESULTS:
      Compared with control, the weight of testis in the high-dose formaldehyde
      exposure group significantly decreased (P < 0.05); the convoluted tubules became
      atrophied, the layers of seminiferous epithelium decreased, the arrangement of
      seminiferous epithelium was in disorder in the medium- and high-dose formaldehyde
      exposure groups; the sperm count and sperm motility significantly decreased (P <
      0.05), the percent of abnormal sperm significantly increased (P < 0.05)in the
      medium- and high-dose formaldehyde exposure groups; the serum testosterone
      content mildly decreased and the serum FSH and LH content mildly increased in the
      formaldehyde exposure groups, but no statistically significant difference was
      observed. Moreover, in comparison with control, the apoptosis rate and the
      expression of Fas gene increased in the testicular tissue of rats in the medium-
      and high-dose formaldehyde exposure groups (P < 0.05). The apoptosis rate was
      significantly correlated with the expression of Fas gene (r = 0.8832, P < 0. 05).
      CONCLUSION: Formaldehyde exerts reproductive toxicity to adult male rats, and Fas
      mediated apoptosis may be one of the functional mechanisms involved in the
      reproductive toxicity of formaldehyde.

PMID- 16909604
TI  - [Effects of perinatal exposure to bisphenol A inducing dopaminergic neuronal cell
      to apoptosis happening in midbrain of male rat offspring].
AB  - OBJECTIVE: To investigate the mechanism and effect of rat perinatal exposure to
      bisphenol A (BPA) resulting in midbrain dopaminergic neuronal cell apoptosis and
      tyrosine hydroxylase expression of male offspring. METHODS: Rat dams were
      randomLy divided into 4 groups on gestational day(GD) 10 and given orally the
      bisphenol A doses as 0, 0.5, 5, 50 mg/kg x d from GD10 to weaning. The brains of
      male offspring were obtained for detecting, with immunohistochemistry protocol,
      the Caspase-3, Bcl-2 and tyrosine hydroxylase expression in the midbrain on
      postnatal day 21 or 30 respectively, and the midbrain apoptotic neuronal cell
      were detected by TUNEL on PND21. RESULTS: The expression of Caspase-3 in the
      midbrain of rat male offspring were increased but bcl-2 were decreased on PND21
      and 30, respectively. On PND21, apoptotic neuronal cell were found in the
      midbrain of high and medium doses groups. TH protein expression was decreased.
      CONCLUSION: Perinatal exposure to bisphenol A can induce the apoptosis of
      midbrain dopaminergic neuron in the male rat offspring even after weaning, and
      concomitantly decrease the midbrain TH immunoreactivity, this may cause the
      abnormal function of dopaminergic pathway of rat male offspring.

PMID- 16909605
TI  - [Effect of intestinal ischemia/reperfusion injury on protein and mRNA levels of
      orexin-A].
AB  - OBJECTIVE: To investigate the effect of intestinal ischemia/reperfusion (I/R)
      injury on orexin-A levels in plasma and hypothalamus, and to find out the role of
      orexin-A in acute inflammatory responses. METHODS: Fifty-four SD rats were
      randomly divided into a sham-operation group and 5 experiment groups. Then we
      established the intestinal I/R injury model of rats and setup the 5 experiment
      groups of 60 min ischemia followed by different periods of time for reperfusion.
      Protein levels of orexin-A in plasma and hypothalamus were measured by
      radioimmunoassay, and the changes of orexin-A mRNA expression in hypothalamus
      were detected by RT-PCR. RESULTS: By analyses on the orexin-A levels in plasma of
      rats before and after injury, no significant change was observed in the 5
      experiment groups (P > 0.05), and the 5 groups' post-injury orexin-A levels in
      plasma and hypothalamus were not significantly different from the sham-operation
      group's (P > 0.05). However, by comparison with the sham-operation group after
      injury, the experiment groups were found to have orexin-A mRNA levels in
      hypothalamus significantly decreased step by step from 60 min ishchemia/30 min
      reperfusion (160' R30') to 160'R150'; the lowest level was seen at 160'R150'; and
      at 160'R240' and I60'R360', the level recovered slowly, but it was still lower
      than that seen in the sham-operation group. CONCLUSION: Orexin-A makes a delayed
      response to intestinal I/R injury and may function as inflammatory cytokine in
      the metabolic disorders caused by acute inflammation.

PMID- 16909606
TI  - [Initial research for effects of vasoactive intestinal polypeptide (VIP) on
      differentiation of human umbilical cord blood derived CD34+ cells into hepatic
      related cells].
AB  - OBJECTIVE: To investigate the effect of vasoactive intestinal polypeptide (VIP)
      on differentiation of hematopoietic stem cells (HSC) into hepatic related cells
      and probe into the possibility that VIP affects HSC transdifferentiation.
      METHODS: Mini MACS assay was used to purify human CD34+ cells from mononuclear
      cell (MNC), the purity of the CD34+ cells was evaluated by flow cytometry. Alpha
      fetal proteins(AFP) in cultured CD34+ cells and their supernatant were measured
      with ELISA assay. Liver tissue markers on CD34+ cells, AFP, albumin (ALB) and CK
      19, were measured by immunohistochemistry. Western blot assay was used to detect
      the expression of ALB on CD34+ cells. Nest RT-PCR was used to measure the
      expression of AFP mRNA and ALB mRNA on CD34+ cells, the product of ALB was chosen
      to measure the sequence. RESULTS: Immunohistochemistry showed that human CD34+
      cell contained AFP and albumin but no CK-19 protein. When human CD34+ cells were
      cultured with VIP for 14 days, the concentration of AFP within CD34+ cells was
      decreased from (270.00 +/- 11.37) pg/mL to (165.00 +/- 8.51) pg/mL (P < 0.05).
      Western blot revealed that albumin in CD34+ cells treated with VIP faded,
      compared to that of control. Both human cord blood MNC and CD34+ cells expressed
      AFP mRNA and albumin mRNA; the sequence of the product of nest RT-PCR for albumin
      matched completely with the sequence of albumin in GenBank. CONCLUSION: Human
      cord blood CD34+ cells have been note to express hepatocyte related markers such
      as AFP and albumin, although there is no evidence of CK-19 expression. These
      findings suggests the possibility that human HSC could be transdifferentiated
      into hepatocyte. The expressions of AFP and albumin on human CD34+ cells
      depressed by VIP indicate that VIP might inhibit the transdifferentiation of HSC.

PMID- 16909607
TI  - [Effect of NO and Fas pathway on T-2 induced apoptosis in chondrocytes].
AB  - OBJECTIVE: To investigate the relationship of T-2 toxin-induced chondrocytes
      apoptosis with nitric oxide(NO) and Fas apoptosis pathway. METHODS: Human
      chondrocytes cultured in vitro were treated with different concentrations of T-2
      toxin at different time (1-5 d). Cell viability of the treated cells was measured
      by MTT assay. Apoptotic ultrostructural changes of the treated cells were
      observed with electron microscopy. Biological changes of apoptosis were detected
      by annexin V/PI Flow cytometer (FCM). The levels of NO in culture media were
      detected by colorimetric method of Griess assay. Nitric oxide synthase (iNOS) and
      Fas protein were measured by Western blot. RESULTS: In this study the results
      shown the dose-dependent and time-dependent effects of T-2 toxin, within a range
      of concentration (1-2000 ng/mL) and a period of time (1-5 d), on the T-2 toxin
      treated chondrocytes. Apoptotic body was found in T-2 toxin-treated chondrocytes
      by electron microscopy. Early-stage apoptosis rate and late-stage apoptosis rate
      were both increased in T-2 toxin-treated cells when compared with non-treated
      cells in a dose-dependent manner. The levels of NO in T-2 toxin-treated culture
      media were higher than that of normal control. Over-expressions of iNOS and Fas
      protein were detected in T-2 toxin-treated cells. T-2 toxin-induced apoptosis was
      noted to be significtnly correlated with the level of NO production and the
      levels of iNOS and Fas protein expression. CONCLUSION: T-2 toxin can enhance NO
      production and upregulate the expression of iNOS and Fas protein. Both NO and Fas
      signaling pathway are involved in T-2 toxin-induced apoptosis.

PMID- 16909608
TI  - [The monitoring of Th1/Th2 cytokine expression and its significance to the
      diagnosis of acute rejection after pancreatic transplantation].
AB  - OBJECTIVE: To investigate the relationship between the change of Th1/Th2 cytokine
      expression in peripheral blood and the acute rejection or immune tolerance after
      pancreatic transplantation. METHODS: Twenty-four pigs of mixed inbreed were
      randomly divided into three groups, namely the control group, the transplantation
      group which was established by pancreatoduodenal allotranplantation, and the
      transplantation plus immunosuppression group which was brought into being in
      accordance to the immunosuppression regimen of CsA, MMF and metrisone after the
      pancreatoduodenal allotransplantation. The changes of the expression of Th1/Th2
      cytokine in CD4+ T cells were detected by flow cytometry on the day before
      operation and on the first, 3rd, 5th ,and 7th day after operation; meanwhile, the
      levels of glucose, insulin and glucagons in systemic circulation were measured,
      and the tissues of pancreatic grafts were collected on the first, 3rd, 5th and
      7th day after operation. RESULTS: IFN-gamma expression was up-regulated sharply
      from the first day to 7th day after transplantation in transplantation group and
      was up-regulated slightly in immunosuppression group. IFN-gamma expression showed
      significant difference between transplantation group and immunosuppression group
      on the first, 3rd, 5th and 7th day after transplantation (P < 0.05). IL-4
      expression was down-regulated continuously in transplantation group, but up
      regulated in immunosuppression group. IL-4 expression exhibited significant
      difference between transplantation group and immunosuppression group on the 3rd,
      5th, and 7th day after transplantation (P < 0.05). In comparison with control,
      the levels of sugar, insulin and glucagons in blood displayed no significant
      difference between transplantation group and immunosuppression group (P > 0.05).
      In comparison with transplantation group, the immunosuppression group showed
      milder rejection on the 5th and 7th day after transplantation (P < 0.05).
      CONCLUSION: Change of expression of Th1 and Th2 cytokines may be an important
      parameter in determining whether acute rejection occurs after pancreatic
      transplantation.

PMID- 16909609
TI  - [A study on the expression of HSP70 in endothelial cells pretreated with ethanol
      and fluid shear stress].
AB  - OBJECTIVE: To detect whether ethanol can affect the expression of HSP70 in
      endothelial cells under fluid shear stress. METHODS: Ethanol at different
      concentrations was added to the culture medium of endothelial cells, EA. Hy926,
      which was treated statically or under 1Pa fluid shear stress. After the
      incubation of 1 h, 2 h, 4 h and 6 h, the expression of HSP70 was detected by
      immunohistochemical method(SP). RESULTS: In the control group, the expression of
      HSP70 was negative under static state, while it was positive under 1Pa fluid
      shear stress lasting 4 h even without ethanol. No statistic difference was found
      between the 50 mg/dL ethanol group and the control group with the same treatment
      time of fluid shear stress. HSP70 expression was found under static state with
      150 mg/dL ethanol after 4 h or 300 mg/dL ethanol after 2 h respectively. The
      expression increased greatly under 1Pa fluid shear stress in the same ethanol
      concentrations. CONCLUSION: Medium to high ethanol concentration in coordination
      with fluid shear stress can strongly stimulates the expression of HSP70 by a
      kinetic mechanism of time-dependent.

PMID- 16909610
TI  - [Experimental study on rat model of endometriosis treated with tamoxifen and
      rhizoma curcumae oil].
AB  - OBJECTIVE: To evaluate the therapeutic effect of Tamoxifen in conjunction with a
      cell apoptosis contributor--Rhizoma curcumae oil on the rat endometriosis models.
      METHODS: The rat endometriosis models were established and were randomly assigned
      into the control group, Tamoxifen group, Alarelin (GnRHa) group, and the group of
      Tamoxifen (by gastrogavage) plus Rhizoma curcumae oil (by intraperitoneal
      injection). After 4 weeks of treatment, the growth of ectopic endometrial
      implants was observed; then eutopic and ectopic endometria were excised in
      preparation for HE staining and streptavedin-peroxi-dase immunohisto chemical
      analysis. RESULTS: After treatment, the volume of the ectopic implants of each
      treatment group was markedly smaller than that of control and before treatment (P
      < 0.05); the score of VEGF showed significant difference when each treatment
      group was compared with control (P < 0.05). The score of VEGF exhibited marked
      difference between Tamoxifen group and Alarelin (GnRHa) group, between Tamoxifen
      group and Tamoxifen plus Rhizoma curcumae oil group (P < 0.05). CONCLUSION:
      Tamoxifen in conjunction with Rhizoma curcumae oil could decrease markedly the
      volume and VEGF expression of ectopic implants.

PMID- 16909612
TI  - [HAI-1 expression in villous tissue of early gestational period in women].
AB  - OBJECTIVE: To survey the role of hepatocyte growth factor activator inhibitor
      type 1 (HAI-1) in early embryo development, we study the HA-1 gene expressing in
      villous tissue after embryo implantation. METHODS: Fifty villous tissue samples
      from pregnant 6 w to 10 w were divided into five groups and each group included
      ten samples. The HAI-1 gene and protein expressing in the villous tissue were
      detected by RT-PCR and immunohistochemistry. RESULTS: The expression of HAI-1 had
      a gradual increase with the pregnancy weeks added. The HAl-1 gene expression was
      very low at pregnant 6 w(A(260/280) 0.3142), From pregnant 7 w to 9 w, the
      expression was increased gradually (A(260/280) 0.3476 in 7 w and 0.3910 in 8 w)
      and reached the pinnacle in 9 w (A(260/280) 0.4876). And then the pinnacle value
      lasted until 10 w (A(260/280) 0.4909). The proportion of HAI-1 mRNA/beta-actin
      mRNA between 9 w and 10 w was not significantly different (P > or = 0.05). But
      among the other 3 groups, the proportion was significantly different (P < 0.01).
      The proportion of 9 w and 10 w was significantly different from the other 3
      groups (P < 0.01). The results of HAI-1 protein expression showed the similar
      conclusion by immunohistochemical analysis. CONCLUSION: The HAI-1 gene may play
      an important role in early embryo development in human.

PMID- 16909611
TI  - [Effects of rosiglitazone on the expression of beta1, integrin and ICAM-1 in high
      glucose-induced rat glomerular mesangial cells].
AB  - OBJECTIVE: To observe the effects of PPARgamma activators thiazolidinediones
      (Rosiglitazone) on the expression of intercellular adhesion molecule-1 (ICAM-1)
      and beta1 integrin in high glucose-induced rat glomerular mesangial cells (GMC)
      in order to elucidate the relationship between PPARgamma and adhesion molecules.
      METHODS: Rat HBZY-1 GMCs were cultured in vitro and divided into 9 groups: Normal
      Glucose group (N), High Glucose group (H), Mannitiol group (M), Normal and High
      Glucose plus 1, 5, 10 micromol/L Rosiglitazone. Every group was treated for 24
      hours. The expression of ICAM-1 was measured by immunohistochemistry, the
      expression of beta1 integrin by indirect immunofluorescence staining and flow
      cytometry. RESULTS: It was found that high glucose can significantly increase the
      expression of ICAM-1 and beta1 integrin in GMCs, which is independent of the
      osmotic pressure. Rosiglitazone can inhibit the expression of ICAM-1 and beta1
      integrin in normal and high glucose treated GMCs, and the inhibition is stronger
      in high glucose treated-group, which is in a dose-dependent manner. The
      expression of beta1 integrin is positively correlated with ICAM-1. CONCLUSION:
      Adhesion molecules involves in the pathogenesis of diabetic nephropathy (DN).
      PPARgamma activators-Rosiglitazone may exert effect on mesangial expansion and
      glomerulosclerosis in DN through the inhibition of expressions of adhesion
      molecules induced by high glucose.

PMID- 16909614
TI  - [The change of nuclear factor-kappa B expression in the lung tissues of chronic
      hypoxic rats].
AB  - OBJECTIVE: To investigate the change of nuclear factor-kappa B (NF-kappaB)
      expression in the lung tissues from chronic hypoxic rats and the role of NF
      kappaB in the pathogenesis of hypoxic pulmonary hypertension. METHODS: Twenty
      male SD rats were randomly divided into two groups: control group and hypoxic
      group. The animal model of pulmonary hypertension was established by exposing the
      rats to normabaric hypoxic conditions for three weeks. The mean pulmonary
      arterial pressure (mPAP) was measured by a right cardiac catheterization. The
      indices of wall thickness of pulmonary arteriole (WT% and WA%) were measured by a
      computerized image analyzer. NF-kappaB expression in lung tissues were observed
      by using immunohistochemistry. RESULTS: (1) The mPAP of hypoxic rats was (29.1 +/
      4.5) mmHg,and it was (16.8 +/- 2.6) mmHg in normal rats, there was significant
      difference between two groups (P < 0.001). (2) In hypoxic group, the WT% was
      (22.36 +/- 2.99)% and WA% was (69.14 +/- 5.38)%; in normal group, WT% was (15.36
      +/- 3.08)% and WA% was (46.75 +/- 6.54)%, the differences were significant (P <
      0.01). (3) Both normal and hypoxic group, there were positive cells for NF-kappaB
      nuclear staining in lung tissues of rats. The percentage of positive cells for NF
      kappaB nuclear staining in bronchiolar epithelial cells was significantly
      increased in the hypoxic group [(29.11 +/- 1.12)%] than that in the control group
      [(12.23 +/- 1.08)%], P < 0.001. CONCLUSION: NF-kappaB expression is increased in
      the lung tissue of rats with chronic hypoxia. It may play a role in the
      pathogenic process of hypoxic pulmonary hypertension.

PMID- 16909613
TI  - [Expressions of estrogen receptor subtypes in epithelial ovarian carcinomas].
AB  - OBJECTIVE: To investigate the expressions of estrogen receptor(ER) subtypes ERa
      and ERP in epithelial ovarian carcinomas. METHODS: One hundred and eighteen
      Norwegian patients with epithelial ovarian carcinoma were included in this study.
      The expressions of ERalpha and ERbeta were examined by means of
      immunohistochemistry. The relationships between protein expressions and
      clinicopathological features and survival were analyzed. Frozen tissues from 10
      cases in which the tumors showed variable ERalpha and ERbeta protein expressions
      were used for Laser capture microdissection (LCM). Cancer cells in each frozen
      section were captured with the LCM method and processed for Western blot
      analysis. RESULTS: Of the 118 tumours, 32 (27.1%), 20 (16.9%), 17 (14.4%), 49
      (41.5%) demonstrated negative, weak, moderate and strong expression of ERalpha
      protein, respectively; 1 (0.8%), 7 (5.9%), 13 (11%), 97 (82.2%) showed negative,
      weak, moderate and strong expressions of ERbeta protein, respectively. There was
      no significant association between ERalpha expression and the clinicopathological
      features such as age, histological type, FIGO stage, histological grade and
      residual tumour size. ERbeta expression was not associated with age, histological
      type,FIGO stage and residual tumour size, but it was significantly associated
      with higher histological grade. In addition, Kaplan-meier analysis revealed that
      high levels of ERbeta expression was significantly associated with a shorter
      overall survival (P = 0.03). CONCLUSION: There are ERalpha and ERbeta expressions
      in epithelial ovarian carcinomas. Higher level of ERbeta protein expression is
      associated with higher histological grade and poorer clinical outcome in the
      cases of ovarian carcinoma. ERbeta may be a useful marker of ovarian
      carcinogenesis and could predict the efficacy of endocrinotherapy and the
      prognosis for patients with ovarian carcinoma.

PMID- 16909615
TI  - [Expression and role of endostatin in the retina of oxygen-induced retinopathy
      mouse model].
AB  - OBJECTIVE: To investigate the effect of endostatin on the pathogenesis and
      development of retinal neovascula animal model of oxygen-induced retinopathy.
      METHODS: The animal model of oxygen-induced retinopathy was made by subjecting
      postnatal mice to hyperoxic conditions (5 days) followed by normoxic conditions.
      Retinal angiogram was taken by using high molecular weight fluorescein-dextran.
      The degree of hyperoxia-induced neovascularization in serial paraffin cross
      sections was quantified by counting the number of vascular cell nuclei on vitreal
      side of the internal limiting membrane. The expression of ES and VEGF in the
      oxygen-induced retina was observed by immunohistochemistry. RESULTS: We
      successfully constructed the oxygen-induced retinopathy mouse model. FITC-dextran
      retinal angiography indicated that hyperoxia could produce constriction of
      retinal vasculature and vaso-obliteration or irreversible closure of many
      capillary channels and eventually result in non-perfused area in the post-area of
      retina surrounding the optic disk. Relatively, hypoxia could lead to dilation and
      torsion of retinal vessels. There were averagely 22 neovascular nuclei per cross
      section of eyes in the hyperoxia group and less than 3 nuclei per cross-section
      of eyes in the control group (P < 0.05). The expressions of ES and VEGF in the
      retina under hyperoxia were stronger than those under normoxia, expecially the
      expression of VEGF. CONCLUSION: Taking measures to up-regulate the expression of
      endogenetic endostatin may have the potential for effective treatment of retinal
      ischemic neovascularization.

PMID- 16909616
TI  - [The relationship of injury timing with the change of neuronal apoptosis and the
      expression of caspase-3 after brain contusion].
AB  - OBJECTIVE: To investigate and analyze the changes of neuronal-apoptosis and the
      expression of caspase-3 for finding out a new method of injury timing after brain
      contusion in human. METHODS: The tissue was stained by TUNEL for apoptosis and by
      immunohistochemistry for caspase-3. Image analysis technique was employed.
      RESULTS: The nerve cells stained positive by TUNEL and Caspase-3
      immunohistochemistry were distributed in the penumbra and central area. Both
      these areas were in striking contrast with the distal area or those of control
      group. The positive staining was more prominente in penumbra area than in central
      area (P < 0.05). The changes of TUNEL staining and expression of Caspase-3 in
      penumbra area gradually increased with the survival period after injury; they
      were parallel to each other. There were linear relationships between the time of
      injury in 48 hours and the increase in the mean of integral optical density
      (IOD), the coefficient of correlation (r) being 0.93 and 0.69 for the two
      staining methods, and two linear regression formulae were induced, respectively.
      CONCLUSION: Observations on the increasing of neuronal apoptosis and Caspase-3
      expression in relation with the survival period after injury could be utilized in
      the timing of brain contusion.

PMID- 16909617
TI  - [Blood leptin, orexins and NPY levels and their relations in obese children].
AB  - OBJECTIVE: To investigate the concentration levels of leptin, orexins and
      neuropeptide Y (NPY) in the blood of obese children, and to analysed the
      relationship between these substances. METHODS: RIA methods were used to measure
      the concentrations of leptin, orexinA, orexinB, and NPY in the blood of 98 obese
      children [BMI: male (29.24 +/- 1.87) kg/mZ, female (28.12 +/- 2.30) kg/m2] and in
      104 normal children [BMI: male (20.49 +/- 1.95) kg/m2, female (19.59 +/- 1.51)
      kg/m2] as the control group. RESULTS: The leptin concentrations in obese children
      [male (26.00 +/- 14.66) ng/mL; female (33.59 +/- 14.63) ng/mL] were higher than
      those in the control group [male (6.65 +/- 44.49) ng/mL; female [10.48 +/- 5.52)
      ng/mL P < 0.013]. The concentrations of plasma orexinA in obes children [male
      (3.23 +/- 1.86) pg/mL; female (3.38 +/- 1.80) pg/mL] were lower than those in the
      control group [male (4.52 +/- 1.52) pg/mL; female (4.71 +/- 1.53) pg/mL P <
      0.05]; Negative correlations between leptin and NPY were noted in the obesity
      group (r = -0.302) and the control group (r = -0.310, P < 0.01), while the slopes
      in the two groups were different (control group -2.969; obese group -0.809). A
      positive correlation between NPY and orexinA was noted (r = 0.207, P < 0.05). The
      fluctuation range of orexinA in obese children was markedly narrowed when
      compared with that in the control group. CONCLUSION: The concentration level of
      peripheral orexinA and leptin in the obese and non-obese children change
      inversely. The obesity in children correlates with the concentrations of orexinA,
      leptin, NPY as well as with their interactions.

PMID- 16909618
TI  - [Proliferation and undifferentiation of spermatogonial stem cells in vitro].
AB  - OBJECTIVE: To investigate the fluences on the proliferation and undifferentiation
      of spermatogonial stem cells in vitro. METHODS: Mouse bone marrow stromal cells
      were subjected to primary culture; when the cells grew up and extended around,
      they were treated with mitomycin C. And then, to the bone marrow stromal cells
      were added spermatogonial stem cells for co-culture. The ambient temperature was
      37 degrees C. RESULTS: The spermatogonial stem cells increased in number
      obviously when cultured for 2-4 days, they could be single, paired or clustered,
      while the differentiated cells began to die; when cultured for 4-8 days, the
      cells proliferated not in a distinct manner, they seemed to be stable; but at 10
      days, the cells began to grow, especially when cultured for 15 days, the cells
      had the characteristic structure of the spermatogonial stem cell; when cultured
      continuously for 25 days, the cells had the same morphology and very clear
      intercellular bridges. CONCLUSION: Spermatogonial stem cells can proliferate and
      continue to be undifferentiated on the bone marrow stromal cells when the ambient
      temperature is 37 degrees C.

PMID- 16909619
TI  - [The intercostal nerve transplantation with olfactory ensheathing cells modified
      by NGF, BDNF genes repairs the injured rat spinal cord].
AB  - OBJECTIVE: To study the repairable effects of intercostal nerve transplantation
      with NGF,BDNF genes modifying olfactory Ensheathing cells (OECs) on spinal cord
      injury (SCI). METHODS: The spinal cord hemisection model was made by cutting 2 mm
      rat spinal cord from T11 and T12. And then the lesion was repaired using
      intercostal nerve linking manner (proximal gray substance to distal white
      substance and L1, L2, L3, L4 of radix posterior and proximal white substance),
      and with NGF, BDNF genes modifying OECs were transplanted into group A. However,
      the group B was only transplanted to get the intercostal nerve but no OECs, the
      group C was without treatment but an absorbable gelatin sponge was used to SCI.
      The operated model rat had been bred for 4 to 8 weeks. The BBB scores were
      checked, and the somatosensory evoked potentials (SEP), motor evoked potentials
      (MEP) were examined, and the tissue structure of the operated region was observed
      under the light microscope. RESULTS: The 8 weeks of after operation, the back
      limbs function of group A rats was recovered, and BBB scores were A>B>C, and the
      peak latencies of early waves in SEP and MEP were A<B<C. With observing group A
      under the light microscope, of which the transplanted nerve was surviving, the
      lesion was filled and partly fused with the spinal tissue. The group A nerve
      function recovery was better than growp B and C. CONCLUSION: The intercostal
      nerve and NGF,BDNF genes modifying OECs transplantation can recover from the
      spinal cord injury.

PMID- 16909620
TI  - [Job burnout and contributing factors for nurses].
AB  - OBJECTIVE: To investigate the degree of job burnout and contributing factors for
      nurses. METHODS: A total of 495 nurses from three provincial hospitals were
      randomly selected. The MBI-GS, EPQ-RSC and OSI-R were administered to measure job
      burnout, personality traits and occupational stress, respectively. RESULTS: The
      medical and surgical nurses had significant greater scores of job burnout than
      others (P < 0.05). The poorer educational background was correlated with lower
      professional efficacy. The younger nurses had stronger feeling of job burnout.
      The scores of job burnout changed with different personality traits. The main
      contributing variables to exhaustion were overload, sense of responsibility, role
      insufficient and self-care (P < 0.05). The main contributing variables to
      cynicism were role insufficiency, role boundary, sense of responsibility and self
      care (P < 0.05). The main contributing variables to professional inefficacy were
      role insufficiency, social support and rational/cognitive coping (P < 0.05).
      CONCLUSION: Job burnout for nurses can be prevented by reducing or keeping
      moderate professional duties and responsibility, making clearer job descriptions,
      promoting leisure activities, and enhancing self-care capabilities.

PMID- 16909621
TI  - [Prevalence and risk factors of social anxiety disorder in high schools and
      universities in Chengdu].
AB  - OBJECTIVE: To explore the prevalence and risk factors of social anxiety disorder
      (SAD) in high schools and universities in Chengdu. METHODS: 2279 students in
      Chengdu sampled by optimum distributing delaminating grouping method were
      interviewed one-to-one by the trained psychiatrists according to SCID. Both the
      cooperated SAD patients (n=156) and the normal counterparts (NC, n=156) in the
      2279 students completed Egma Minnen av Bardndosnauppforstran (EMBU), State-Trait
      Anxiety Inventory (STAI-Form Y), Fear of Negative Evaluation Scale (FNE) and
      Defense Style Questionnaire (DSQ). RESULTS: There were 179 SAD patients, 88
      female ones and 91 male ones, in the 2279 students of the high schools and
      universities in Chengdu. Statistical analysis reveals that the SAD patients
      differ from the NC in seven aspects, i.e. growing circumstances (P = 0.049),
      family economical status(P = 0.000), family history of psychiatric disorder,
      scales of EMBU,STAI, FNE and DSQ. CONCLUSION: The total prevalence of SAD in the
      students of high schools and universities in Chengdu was 8.15%, the female
      prevalence 8.35%, and the male prevalence 7.62%. The possible risk factors were:
      growing up in the countryside, low family economic state, parental rearing
      pattern being deficient in emotional warmth, understanding, trust and
      encouragement but excessive in refuse, denial and overprotection, having anxiety
      trait, feeling fear of negative evaluation, more likely to use neurotic and
      immature defense mechanism while less likely to use mature defense mechanism,
      having positive family mental disorder history.

PMID- 16909622
TI  - [A clinicopathologic analysis of primary ovarian non-Hodgkin's lymphoma].
AB  - OBJECTIVE: To observe the clinicopathologic manifestations and to investigate the
      clinicopathologic features and diagnosis of primary ovarian non-Hodgkin's
      lymphoma. METHODS: A retrospective study of clinicopathology was made for 15
      cases of primary ovarian non-Hodgkin's lymphomas. The histological classifying
      was based on the WHO classification for tumors of hematopoietic and lymphoid
      tissues (2001). Immunophenotype analysis was made by SP method. RESULTS: This
      kind of tumor was accounted for 0.56% of all non-Hodgkin's lymphoma (NHL)
      received in the same period. In all 15 cases, the patients of stage III and IV
      were 12 (80%), and stage I and II were 3 cases (20%). Histological
      classification: all 15 cases (100%) were diffuse large B cell lymphoma (DLBCL),
      centroblast or immunoblast types. All patients had received operation; three of
      them also received chemotherapy of CHOP or COMP. The follow-up data was available
      for 4 cases, and all of them died within period of 21 days to 18 months.
      CONCLUSION: Primary ovarian non-Hodgkin's lymphoma is rare and the prognosis is
      usually poor. Establishment of the diagnosis is based on pathological biopsy and
      immunophenotype analysis. Owing to the diagnosis made usually after most cases
      operated, the surgical treatment is still the essential, and the chemotherapy and
      radiotherapy are also adjuvant for the tumor.

PMID- 16909623
TI  - [Synthesis of 5-fluorouracil derivatives containing alkanoic acid].
AB  - OBJECTIVE: To synthesize 5-fluorouracil derivatives containing 2-5 carbon
      alkanoic acid. METHODS: N1-substituted derivatives containing alkanoic acid were
      prepared through the hydrolysis of these products of the reaction of haloesters
      and excessive amount of 5-fluorouracil. 5-fluorouracil were protected with
      tertbutoxycarbonyl (Boc) at N1-position, then reacted with haloesters and
      deprotected in turn, through this "one-pot" method, N3-substituted 5-FU alkanoic
      acid esters can be obtained, with high yields (75%-85%). The hydrolysis of these
      products gave N3-substituted 5-FU alkanoic acid at last. RESULTS: Including 10
      new compounds and 8 aim compounds, 16 derivatives of 5-fluorouracil were obtained
      and confirmed by the spectral detection. CONCLUSIONS: The reaction of excessive
      amount of 5-fluorouracil and haloesters can produce a good yield of N1
      substituted derivatives. N3-substituted derivatives can be obtained through the
      reactions of 5-fluorouracil protected with Boc at N1-position and haloesters.

PMID- 16909624
TI  - Fifty years of the parietal cortex: What could we tell Critchley today?

PMID- 16909625
TI  - Polyopic heautoscopy: Case report and review of the literature.
AB  - Heautoscopy, i.e., the encounter with one's double, is a multimodal illusory
      reduplication of one's own body and self. In its polyopic form, more than one
      double is experienced. In the present article, we review fourteen published cases
      of polyopic heautoscopy and describe in detail the case of a 41-year-old man with
      polyopic heautoscopy resulting from a tumor in the insular region of the left
      temporal lobe. Our case is illustrative in several respects: (1) The patient's
      five doubles were all confined to the right hemispace. Laterality in this case is
      discussed with reference to previous cases of unilateral heautoscopy after focal
      brain damage, which generally do not show a hemispatial or hemispheric bias. (2)
      The patient's psychological affinity with his doubles, and also the extent of
      their echopraxia of his movements, decreased as a function of their perceived
      spatial distance from the patient's body, corroborating previous observations of
      associations between spatial and psychological phenomenologies during autoscopic
      phenomena. (3) While classical heautoscopy (the reduplication of a single body
      and self) is considered a breakdown in the integrative processes that enable us
      to identify our self with our body, the phenomenon of polyopic heautoscopy (a
      multiplication of body and self) points to the multiple mappings of the body,
      whose disintegration may give rise to the illusory experience of multiple selves.

PMID- 16909626
TI  - Semantic knowledge in mild cognitive impairment and mild Alzheimer's disease.
AB  - The aim of this study was to investigate memory in patients with mild cognitive
      impairment (MCI) and mild Alzheimer's disease (AD). Ten patients with MCI, 11
      with AD and a group of age and education matched healthy control participants
      were assessed on a comprehensive battery of semantic memory tests, including
      traditional semantic memory measures and a non-verbal test of knowledge of object
      use. The MCI group was impaired on tests of category fluency and all three
      conditions of an object knowledge test (matching to recipient, function and
      action), plus a difficult object-naming test. The mild AD group showed additional
      impairments on traditional measures of semantic memory, including naming high
      frequency items, comprehension and semantic association. Together these findings
      suggest that semantic memory impairments occur early in the course of AD, more
      specifically in patients with "amnesic" MCI, and provide further evidence that
      impaired category fluency reflects semantic breakdown.

PMID- 16909627
TI  - Approaches to subjective midpoint of horizontal lines in unilateral spatial
      neglect.
AB  - Patients with unilateral spatial neglect usually bisect longer lines with greater
      rightward errors, while they sometimes err leftward for very short lines (e.g.,
      25 mm). We analysed movements of eye fixation from the time before line
      presentation to elucidate whether patients with neglect approach the subjective
      midpoint differently for lines of various lengths. Four patients with left
      neglect bisected 200 mm, 100 mm, and 25 mm lines that appeared across the centre
      of a liquid crystal display (LCD) monitor. The fixation immediately before line
      presentation was located on average near the centre of the lines. Three of the
      patients approached the subjective midpoint point directly from the left side in
      more than 70% of the 200 mm and 100 mm trials. The subjective midpoint frequently
      deviated leftward on the "attended" segment between the leftmost point of
      fixation and the right endpoint, while it was displaced rightward on the total
      extent. The three patients initially explored the 25 mm lines searching for the
      left endpoint. They thereafter bisected the same lines with leftward errors
      approaching the subjective midpoint from the left side. The remaining patient
      searched beyond the right endpoint and in turn approached the subjective midpoint
      from the right side in about half of the trials and independently of line length.
      In the 200 mm and 100 mm trials, the subjective midpoint divided the attended
      right segment nearer to the right endpoint. On the attended right extent of a
      line, patients with neglect may place the subjective midpoint toward the side
      from which they approached that point. In the bisection of very short lines,
      approaches from the left endpoint may cause leftward errors of the subjective
      midpoint. For longer lines, however, approaches from the left side may result in
      rightward error of bisection for the total length, as the leftward extent from
      the fixation immediately before line presentation is hardly explored.

PMID- 16909628
TI  - The eyes have it: Oculomotor exploration and line bisection in neglect.
AB  - In this issue of Cortex, Ishiai et al. (2006) report the eye movements of
      patients with left neglect during the bisection of lines of different lengths.
      This is the latest in a series of papers from Ishiai's group, which form an
      important corpus of data on the oculomotor behaviour of neglect patients during
      line bisection and related tasks. In this article, I argue that these data should
      critically constrain theoretical models of bisection errors in neglect, but that
      these constraints have been applied rarely in practice. First, I briefly
      introduce bisection behaviour in neglect and describe some of the models proposed
      to account for its character. I then consider the implications for these models
      of Ishiai and colleagues' observations. Finally, I outline a novel view of the
      bisection task that is more compatible with their observations.

PMID- 16909629
TI  - The right arm likes to be close.
AB  - A prior study revealed that the left (vs. right) hemisphere has a visual
      attentional bias toward the body, a finding that is consistent with the
      observation that most of the visual cognitive activities performed by the left
      hemisphere (e.g., reading) take place in proximal (peripersonal) space. In
      addition, when right-handed people perform bimanual motor tasks their right hand
      is often held more proximal to the body than their left hand. In this study, we
      wanted to test the hypothesis that the right hand is also more biased toward the
      body than is the left hand. Thus, we had blindfolded right-handed subjects
      attempt to draw straight horizontal lines (at the junction of the transverse and
      coronal planes), with their left and right hands, on sheets of paper placed in
      front of them and then measured their deviation from the coronal plane. We found
      that these subjects' right hands deviated closer to their body than did their
      left hands. These results support the postulate that in addition to an
      attentional bias, the left hemisphere-right hand has a proximal motor bias. This
      bias might account for means by which right-handed people position their hands
      when using both hands on tools and implements.

PMID- 16909630
TI  - Processing of emotional facial expressions in Korsakoff's syndrome.
AB  - Interpersonal contacts depend to a large extent on understanding emotional facial
      expressions of others. Several neurological conditions may affect proficiency in
      emotional expression recognition. It has been shown that chronic alcoholics are
      impaired in labelling emotional expressions. More specifically, they mislabel sad
      expressions, regarding them as more hostile. Surprisingly, there has been
      relatively little research on patients with Korsakoff's syndrome as a result of
      chronic alcohol abuse. The current study investigated 23 patients diagnosed with
      Korsakoff's syndrome compared to 23 matched control participants. This study is
      the first to make use of a newly developed sensitive paradigm to measure emotion
      recognition for several emotions (anger, disgust, fear, happiness, sadness and
      surprise). The results show that patients with Korsakoff's syndrome are impaired
      at recognizing angry, fearful and surprised facial emotional expressions. These
      deficits might be due to the reported sub-cortical brain dysfunction in
      Korsakoff's syndrome.

PMID- 16909631
TI  - Sense of motor effort in patients with schizophrenia.
AB  - We tested the hypothesis suggesting that internally generated signals related to
      motor command would not be processed in schizophrenic patients with first rank
      symptoms (FRS). To address this question, we investigated an aspect of the
      efference copy not yet investigated in schizophrenia, namely its implication in
      sensation of effort. We assessed sensation of effort in healthy subjects (n = 17)
      and in schizophrenic patients with (n = 6) and without (n = 11) FRS using two
      tasks. In the first, subjects were required to produce isometric target-forces
      under visual control with one hand (reference hand), and then, without external
      feedback, to transfer the same effort to the other hand (matched hand). In the
      second, subjects had to produce force impulses whose magnitude was proportional
      to numerical values. The results of the first experiment showed that all subjects
      could maintain a significant relationship between the force exerted by the
      reference hand and the force exerted by the matching hand. Results from the
      second experiment indicated that the strength of the relationship between desired
      efforts and achieved peak forces was lower in both patient groups compared to
      controls. Taken together our findings indicate that one component of efference
      copy--its implication in sensing achieved effort--is preserved in schizophrenia.
      We propose that schizophrenic patients and particularly those with FRS are
      impaired in the ability to represent intended effort. The detection threshold of
      centrally generated signals by the higher order level of the motor representation
      may be abnormally high in these patients.

PMID- 16909632
TI  - The role of the posterior parietal lobe in prism adaptation: Failure to adapt to
      optical prisms in a patient with bilateral damage to posterior parietal cortex.
AB  - We studied a patient (J.J.) with bilateral damage to those regions of the
      posterior parietal cortex (PPC) thought to be involved in prism adaptation. We
      demonstrated, for the first time in a parietal patient, that J.J. was unable to
      adapt to the visual perturbation induced by the optical prisms with either hand
      within four times the number of trials required by healthy adult subjects. We
      offer a novel account for the role of the PPC in prism adaptation: that the reach
      direction to the veridical target location specified in extrinsic limb-based
      coordinates must be de-coupled from the gaze direction to the perceived target
      location specified by intrinsic oculocentric coordinates in order to produce
      spatially accurate movements. This spatial discrepancy between gaze direction and
      reach direction may provide the necessary training signal required by the
      cerebellum to update the current internal model used to maintain spatial
      congruency between visual and proprioceptive maps of peripersonal space. The
      hypothesis is discussed in relation to recent disconnectionist accounts of optic
      ataxia.

PMID- 16909633
TI  - Oculomotor functions of the parietal lobe: Effects of chronic lesions in humans.
AB  - This review summarises research in patients with chronic lesions of parietal
      oculomotor cortex and compares their oculomotor performance to patients with
      lesions of the frontal eye field (FEF). The observations identify the oculomotor
      functions for which these regions are indispensable, and explore dynamic
      interactions within cortical and subcortical networks for oculomotor control. The
      experiments examined endogenously generated saccades, saccades to visual targets,
      antisaccades, saccade choice and saccade remapping for inhibitory spatial
      tagging. The findings suggest that the key function of parietal oculomotor cortex
      is the computation of sensorimotor transformations, rather than the initiation of
      either voluntary or reflexive saccades. They also reveal the re-organisation of
      cortico-subcortical networks after brain injury, and provide insight into their
      dynamic interactions: FEF lesions result in disinhibition of reflexive saccades
      toward the contralesional field and an impairment of reflexive saccades toward
      the ipsilesional field; whereas parietal lesion result in the opposite pattern.

PMID- 16909634
TI  - Dorsal simultanagnosia: An impairment of visual processing or visual awareness?
AB  - When presented with two objects patients with simultanagnosia show a marked
      impairment at naming both items. This has led many authors to conclude that the
      second item is not being processed (e.g., Robinson, 2003). However, this deficit
      may instead reflect a deficit with explicit, or conscious report. We investigated
      this issue using a semantic priming paradigm that allowed us to assess implicit
      processing of the second "unseen" item. We presented a patient, with bilateral
      parietal damage, with pairs of pictures that were either from the same or a
      different semantic category. The patient was asked to either classify one of the
      pictures or to name both pictures. When the items were from different categories
      the patient's classification performance was significantly poorer than when they
      were from the same category, even though he could rarely explicitly report both
      items. These findings are consistent with the notion that the meaning of the
      "unseen" item influenced the reporting of the "seen" item. Consequently, the
      deficit seen in this patient does not seem to reflect an inability to process
      more than one item simultaneously but rather a deficit in explicitly identifying
      multiple items.

PMID- 16909635
TI  - Differential effects of transcranial magnetic stimulation of left and right
      posterior parietal cortex on mental rotation tasks.
AB  - A recently published study used the interference strategy of transcranial
      magnetic stimulation (TMS) to demonstrate the role of the right posterior
      parietal cortex (PPC) in the mental rotation of alphanumeric stimuli. We used
      similar stimulation parameters over the same left and right PPC regions, and
      examined the ability to rotate more complex 3D Shepard and Metzler (1971) images.
      There was reduced accuracy of performance with both right and left PPC
      stimulation for different angles of rotation of the visual stimuli. Right PPC
      stimulation led to reduced accuracy to rotate stimuli by 1200, whereas left PPC
      stimulation affected 180 degrees C rotation. We hypothesise that the two
      hemispheres make different contributions to the processing underlying
      visuospatial mental imagery: the right PPC is important for spatial rotations
      through smaller angles; the left hemisphere has a unique role when the stimuli to
      be compared are rotated through 180 degrees C, a task that engages verbal
      strategies due to the well-documented special nature of enantiomorphs.

PMID- 16909636
TI  - Do parietal cortical lesions impair spatial attention or allocentric spatial
      perception?
AB  - It remains unclear whether monkeys with large parietal cortical lesions fail
      "landmark" tasks because they cannot judge the relative distances between
      landmark and response locations, or because they fail to attend to, or even to
      notice, the landmark. Monkeys with small posterior parietal (SPP), large
      posterior parietal (LPP), superior temporal sulcus (STS), or frontal eye field
      (FEF) lesions were tested on a landmark task in which the physical salience of
      the landmark and its location varied. Only the LPP monkeys were impaired,
      seemingly because they overtly failed to shift attention during each trial,
      responding to whichever food well they looked at first. A task based on one used
      with neurological patients was therefore introduced in which the monkeys had to
      discriminate between two white square plaques each containing a spot, where the
      spot on the positive stimulus was centrally placed. Solving this task requires an
      allocentric judgement about the relative location of each spot to the edges of
      the plaque. Even on the most difficult discrimination, monkeys with large
      parietal lobe lesions were unimpaired. The deficits previously reported on
      landmark tasks probably reflect a failure of spatial attention or attention to
      objects rather than an inability to judge allocentric spatial relationships.

PMID- 16909637
TI  - Disorders of visual attention and the posterior parietal cortex.
AB  - Traditionally, both the monkey and human posterior parietal cortex (PPC) have
      been considered to have a privileged role in spatial perception or action.
      Lesions to this region of the human brain, particularly of the right hemisphere,
      undoubtedly lead to spatially lateralised deficits such as visual extinction or
      neglect. However, although studies in monkeys have revealed much about the
      spatial functions of the parietal lobe, the monkey PPC may not be a good model
      system with which to understand fully the disorders of attention that follow
      damage to the human parietal cortex. Several lines of evidence, from functional
      imaging as well as investigations of patients with parietal damage, demonstrate
      that parts of the human inferior parietal lobe (IPL) have non-spatial functions.
      Here, we argue that it is important to distinguish spatially lateralised from
      spatial deficits. Both spatial and non-spatial impairments might, in principle,
      contribute to a spatially lateralised behavioural syndrome such as neglect. In
      this review, we discuss the evidence for such a proposal and suggest that a
      better understanding of human parietal syndromes may emerge from considering both
      the spatial and non-spatial functions of this region.

PMID- 16909638
TI  - Inferior parietal rtms affects performance in an addition task.
AB  - Neuropsychological and neuroimaging studies strongly suggest that the inferior
      parietal cortex is important for calculation. However, the evidence from
      neuroimaging experiments for a left hemispheric dominance in calculation is not
      as clear as one would expect from the studies of patients. Often a concomitant
      activation of the homologous inferior parietal region of the right hemisphere is
      reported in the same tasks. The objective of this study was to replicate basic
      findings of acalculic patients and to investigate discrepancies between data from
      patients and results from neuroimaging studies in an addition task. Repetitive
      transcranial magnetic stimulation (rTMS) was applied over inferior parietal areas
      and the adjacent intraparietal sulcus (IPS) while subjects solved double-digit
      addition tasks. From studies of acalculic patients it was hypothesised that left
      hemispheric rTMS stimulation should result in longer reaction times (RTs) in the
      addition task. On addition trials without TMS subjects showed the classical
      problem size effect with longer RTs the larger the sum of the two operands.
      Magnetic stimulation over left inferior parietal areas disrupted performance
      significantly. The effect was specific to the left hemisphere stimulation. There
      was no increase in RTs for rTMS stimulation over the right hemisphere.

PMID- 16909639
TI  - Short memoir of Dr. MacDonald Critchley.

PMID- 16909640
TI  - 'The Lady in the Lake' case. Speech given at the BAFS Friends' Dinner on 23
      february 2006.

PMID- 16909641
TI  - Severe (psychopathic) personality disorder: a review.
AB  - The development of the concept, causes and management of severe (psychopathic)
      personality disorder is reviewed against the current background of government
      concern about the activities of a small group of individuals alleged to be
      showing the disorder to a dangerous degree. The authors acknowledge the problems
      involved in 'labelling' the disorder. The term psychopathic has a somewhat
      chequered history. It did not enter U.K. legislation until the Mental Health Act
      1959. To this extent, it is a legal term and does not equate to any exact degree
      with the clinical descriptions currently in use. However, the term 'psychopathic
      disorder' will be used as a kind of shorthand for variants in everyday use. It is
      important to note that in this contribution we are only considering those
      'psychopaths' who have come to the attention of the criminal justice and mental
      health systems. There are also 'psychopaths' who, for a variety of reasons, have
      not come to official attention and a recent contribution by Board and Fritzon
      (2005) highlights some interesting common characteristics in business managers
      and a sample of forensic patients detained in high security establishments.

PMID- 16909642
TI  - The international criminal tribunal for the former Yugoslavia (ICTY) and the
      forensic pathologist: ethical considerations.
AB  - Since 1991, war crimes in the former Yugoslavia have been the subject of several
      international medico-legal investigations of mass graves within the framework of
      inquiries led by the International Criminal Tribunal for the former Yugoslavia
      (ICTY). Forensic pathologists involved in the ICTY missions could be subjected to
      ethical tensions due to the difficulties of the missions, the emergent conflicts
      between forensic scientists of the investigating teams and the original nature of
      the ICTY proceedings. In order to study the nature of such ethical tensions, we
      sent a questionnaire to 65 forensic pathologists who have been involved in the
      ICTY missions. The rate of response was 38%. The majority of forensic
      pathologists questioned (n=18) did not know how the medico-legal data was
      exploited by the ICTY. Three of them have been subjected to pressures. Three of
      them were aware of mass grave sites knowingly not investigated by the ICTY.
      Fifteen considered that the ICTY respected the elementary rules of the law and
      four of them questioned the impartiality of the justice led by the ICTY. Two
      conflicting types of ethics can be drawn from these results: conviction ethics,
      which are shared by most of the forensic pathologists questioned, and
      responsibility ethics. In the former, the forensic pathologist completely agrees
      with the need for an international war crimes tribunal, even if such justice can
      be challenged regarding the respect of human rights and impartiality. In the
      latter, he or she needs to conduct him or herself in ways that do not infringe
      impartiality. As medical deontology duty requires impartiality ethics, discursive
      ethics are needed to ease ethical tensions and to suggest ethical guidelines.
      Alternatives to international justice, through a truth and reconciliation
      commission and by way of humanitarian missions combining victims' identification
      with forensic investigations for historical purposes, could be considered.

PMID- 16909643
TI  - An introduction to computer forensics.
AB  - This paper provides an introduction to the discipline of Computer Forensics. With
      computers being involved in an increasing number, and type, of crimes the trace
      data left on electronic media can play a vital part in the legal process. To
      ensure acceptance by the courts, accepted processes and procedures have to be
      adopted and demonstrated which are not dissimilar to the issues surrounding
      traditional forensic investigations. This paper provides a straightforward
      overview of the three steps involved in the examination of digital media:
      Acquisition of data. Investigation of evidence. Reporting and presentation of
      evidence. Although many of the traditional readers of Medicine, Science and the
      Law are those involved in the biological aspects of forensics, I believe that
      both disciplines can learn from each other, with electronic evidence being more
      readily sought and considered by the legal community and the long, tried and
      tested scientific methods of the forensic community being shared and adopted by
      the computer forensic world.

PMID- 16909644
TI  - The role of drugs and alcohol in rape.
AB  - Alcohol and drugs have been inextricably linked with sexual assault. Media
      coverage has increasingly highlighted the health risks facing intoxicated women
      and more recently identified the risk of rape as an additional hazard. Using a
      sample of rape cases reported to the police between 1999 and 2004, this paper
      establishes that rapes involving intoxicants (alcohol and/or drugs) are
      distinguishable from those which do not. Further analysis discovered that the
      identity of the intoxicated parties (i.e. men, women, neither or both) is
      important in differentiating rapes. Results report differences by location of
      assault, victim offender relationship, victim and offender characteristics and
      offence behaviours. A consistent finding from the analysis is that the victim's
      state of sobriety or inebriation appears more significant than that of the
      offender. The implications for crime prevention and directions for future
      research are discussed.

PMID- 16909645
TI  - Section 5(2) Mental Health Act 1983: does teaching make a difference?
AB  - There have been well-documented misunderstandings about the use and powers of
      section 5(2) of the Mental Health Act (MHA) 1983, however there are no published
      studies looking at how education of the clinicians involved affects any outcome
      measures. The aim of this study was to examine the impact of training junior
      doctors in the correct use and powers of section 5(2) of the MHA 1983. Data was
      collected before and after teaching junior doctors in Nottingham. There were
      proportionally fewer section 5(2)s MHA 1983 implemented by junior doctors after
      the teaching. A suggested gold standard for reclassification rates was found and
      trends in better practice are also reported. Teaching junior doctors about
      section 5(2) MHA 1983 increases the proportion of senior doctors implementing the
      section and this should improve patient care. All junior doctors should receive
      specific teaching about section 5(2) at the start of their training.

PMID- 16909646
TI  - A fatal fall from a balcony? A biomechanical approach to resolving conflicting
      witness accounts.
AB  - An adult male was found below a third floor balcony having sustained fatal head
      injuries. An account provided by a witness described how the deceased had been in
      high spirits and had engaged in swinging from the third floor balcony rail in an
      attempt to swing onto a lower second floor balcony and whilst doing so had lost
      his grip and fallen (10.67 metres) to the ground below. A conflicting account was
      provided, some weeks later, by a second witness, who claimed to have observed an
      argument between two men on a third floor balcony, during which one had
      vigorously pushed the other over the balcony rail. The push, it was alleged,
      caused the man to move very quickly over the balcony rail and fall in an
      'upturned crucifix' position to the ground. This paper describes a series of
      biomechanical experiments, conducted on a reconstruction of the third floor
      balcony and the second floor balcony rail, during which a volunteer was subjected
      to the two fall scenarios, in an attempt to resolve the conflicting witness
      accounts. Analysis of human movement was performed using a 3-D motion analysis
      system, markers were placed at the volunteer's key joint centres and were tracked
      to determine physical parameters. The parameter values were used to calculate
      what dynamic movements may have occurred had the volunteer been allowed to fall,
      not just a distance equivalent to the lower balcony rail but a greater distance,
      equivalent to that between the balcony and the ground. Calculations indicate that
      during the hanging-fall scenario a range of body rotation was produced between
      159 degrees and 249 degrees, that is, an upturned head-first body orientation,
      consistent with that required to produce the described injuries and consistent
      with the description provided by the first witness. The push-fall scenario,
      however, produced a greater estimated body rotation of between 329 degrees and
      530 degrees, equal to the body rotating, from the point of free-fall to the
      moment of impact, between almost 1 and 1.5 times. This was consistent with the
      described injuries but inconsistent with the description provided by the second
      witness. It was therefore concluded that although both the accidental and
      inflicted-push scenarios could produce a body orientation consistent with the
      reported injuries, only the accidental scenario produced a fall which could be
      described as an 'upturned crucifix', since the push scenario produced a
      significantly greater body rotation. The witness who alleged that the deceased
      had been pushed later retracted his statement.

PMID- 16909647
TI  - The future of medium secure forensic psychiatry in Britain: a survey.
AB  - The number of National Health Service (NHS) secure psychiatric beds is
      increasing. This survey asked forensic services about their plans for expansion.
      The survey indicated a large increase in medium secure provision over the next
      five years. The increase in the number of patients being detained in secure
      settings raises questions about whether there is in Britain an on-going process
      of 'reinstitutionalisation' of the mentally ill.

PMID- 16909648
TI  - Migration psychosis and homicide in Singapore: a five year study.
AB  - Psychiatric research into violent offences, particularly murder, have been scant
      in the South East Asian region, with the last major review of homicides in
      Singapore and their association with psychiatric disorders being as far back as
      1985. This study seeks to update the psychiatric community on individuals charged
      with murder in Singapore from 1997 to 2001 and particularly to further
      investigate the phenomenon of 'migration psychosis' in relation to foreigners in
      this sample who have committed homicide. One hundred and ten individuals in
      Singapore were charged with murder between 1997 and 2001. Socio-demographic data,
      psychiatric diagnoses, offence and victim profiles and court outcomes were
      obtained. The group consisting of offenders who were Singapore citizens or
      permanent residents was compared with those offenders who were foreigners.
      Analysis was done using the statistical package, SPSS. The proportion of
      foreigners in this study who committed homicide is significantly higher than the
      proportion of citizens/permanent residents in the general population. Foreigners
      who commit homicide also appear to (i) suffer from the more serious psychiatric
      illnesses of mood and psychotic disorders compared with locals, (ii) be less
      likely to have a known history of violence or a past forensic history and (iii)
      be more likely to be new to psychiatric services compared with the local homicide
      offenders. Compared with locals, foreigners appear to have a higher risk for
      committing homicide. Yet, they are less likely to appear early enough before
      mental health services. Some form of basic education to employers of foreigners
      as well as to the foreigners themselves on the early signs of mental illness is
      recommended.

PMID- 16909649
TI  - Muti killing: a case report.
AB  - Muti killings are a form of murder committed by certain African tribes in South
      Africa and other African countries. Body parts for medicinal and ritualistic
      purposes are removed whilst the victims, mostly women and children, are still
      alive. The authors report the case of a 10-year-old boy who was found in an
      unconscious state in the undergrowth near a rural village in Limpopo, South
      Africa. He had several injuries which included the removal of his private parts
      and severe head injuries. The incidence, etiological and cultural factors,
      predisposing conditions and legal questions arising from such deaths are
      discussed.

PMID- 16909650
TI  - Accidental strangulation of a mentally retarded patient by a clothing collar: a
      case report.
AB  - A 40-year-old mentally retarded woman died of accidental strangulation in a
      nursing home. She was found in a kneeling position with her hands on her knees
      and the collar of her clothing compressing the front and sides of the neck.
      Before the accident, a nurse had dressed the patient in one-piece overall-style
      pyjamas put on back to front so that she could not remove the garment herself.
      The post-mortem findings and reconstruction of the scene of death suggested that
      the patient had been strangled by the collar of her backward-facing clothing
      while in a kneeling position. Because patients with psychiatric illnesses may
      have a limited ability to recognize or communicate symptoms of physical danger,
      they must be closely monitored by knowledgeable medical and nursing staff. This
      case highlights the importance of preventing the accidental deaths of mentally
      retarded patients in nursing homes.

PMID- 16909651
TI  - Suicide by combined insulin and glipizide overdose in a non-insulin dependent
      diabetes mellitus physician: a case report.
AB  - A case of self-injected insulin intoxication with an oral hypoglycaemic agent
      glipizide overdose in a type-II/non-insulin dependent diabetes mellitus (NIDDM)
      individual, a physician by profession, is presented with a review of the
      literature. The case demonstrates the need for thorough scene investigation,
      perusal of clinical details and complete autopsy to certify the death caused by
      combined insulin and glipizide overdose, and the manner of death. A meticulous
      search in the English literature reveals that hardly any fatal cases of combined
      insulin and glipizide overdose have been reported, with almost no cases from
      India, thus making this case report relevant and unique.

PMID- 16909652
TI  - Fatal heat injury incident in a private home for elderly people: a case report.
AB  - This report presents a case in which an 84-year-old elderly female resident of a
      private home for the aged was fatally injured by a young male member of staff.
      The deceased suffered from senile dementia, and died from heat shock due to
      prolonged exposure to an electric fan heater. The heater had been placed
      immediately in front of the woman's body for approximately 2.5 hours, and the
      deceased could not escape from the heat by herself. Major autopsy findings were
      marked second degree burns (predominantly) and smaller areas of first degree
      burns observed on the anterior body surface (chiefly the face, lower abdomen,
      forearm and thigh). The burns area exceeded one-third of the entire body surface.
      Only a small amount of dark red blood (36g) remained in the heart cavity: this
      was fluid but remarkably condensed. Petechial bleeding was observed in areas such
      as the palpebral conjunctivae and renal pelvic mucosae. This case generated great
      public attention as the assailant, who had been employed exclusively for three
      nights' duty per week, had been regarded as very diligent and kind; inflicting
      such a lethal injury appeared out of character. Several important issues related
      to managing residential care facilities for the elderly (in particular, the
      stress associated with night duty caring for the aged with senile dementia, and
      the mental health care of the staff themselves) were disclosed and are discussed
      herein from a medico-legal viewpoint.

PMID- 16909653
TI  - Parks as shibboleths.

PMID- 16909654
TI  - A graduate education framework for tropical conservation and development.
AB  - Conventional graduate training related to tropical conservation and development
      has typically separated the two fields, with students focusing on either
      conservation from the perspective of the biophysical sciences or development as
      an extension of the social sciences. On entering the workforce, however graduates
      find they are required to work beyond disciplinary boundaries to address the
      complex interconnectivity between biological conservation and human well-being.
      We devised a framework for graduate education that broadens students' skill sets
      to learn outside their immediate disciplines and think in terms of linked
      socioecological systems, work in teams, communicate in nonacademic formats, and
      reflect critically on their own perspectives and actions. The University of
      Florida's Tropical Conservation and Development program has adopted a learning
      and action platform that blends theory, skills, and praxis to create an
      intellectual, social, and professionally safe space where students, faculty, and
      other participants can creatively address the complex challenges of tropical
      conservation and development. This platform operates within a nondegree-granting
      program and includes core courses that are taught by a team of biophysical and
      social scientists. It incorporates a range of alternative learning spaces such as
      student-led workshops, retreats, visiting professionals, practitioner
      experiences, and a weekly student-led seminar that collectively encourage
      students and faculty to enhance their skills and systematically and thoroughly
      reflect on program activities. Challenges to the described approach include
      increased service demands on faculty, a redefinition of research excellence to
      include effective and equitable collaboration with host-country partners, and the
      trade-offs and uncertainties inherent in more collaborative, interdisciplinary
      research. Despite these challenges, growing interdisciplinary programs, coupled
      with adaptive educational approaches that emphasize learning and action networks
      of students, faculty, and field partners, provide the best hope for responding to
      the emerging challenges of tropical conservation and development.

PMID- 16909655
TI  - An evaluation of threatened species categorization systems used on the American
      continent.
AB  - Endangered species lists are important tools in conservation. It is essential
      that these lists be prepared using categorization systems that objectively assess
      species extinction risk. To determine which threatened species categorization
      system is the most appropriate and the virtues and limitations of systems used on
      the American continent, we evaluated 25 categorization systems from 20 countries.
      These systems included examples of international lists, most national systems
      used on the American continent, and some systems independently proposed by
      academics. We based our assessment on 15 characteristics that categorization
      systems should have, in terms of categories, criteria, and other relevant issues,
      in order to evaluate species conservation status objectively. Of all evaluated
      systems, the current World Conservation Union system is the most suitable for
      assessing species extinction risk. Most categorization systems, but particularly
      national systems, have serious deficiencies and need to be improved
      substantially. We recommend governments use three types of lists: (1) threatened
      species lists constructed following a sound categorization system, (2) lists of
      species of conservation priority, and (3) lists that serve as normative tools
      (e.g., Convention on International Trade in Endangered Species of Wild Fauna and
      Flora). Additionally, the information used to categorize species should be
      explicit and available to the public. To make the most of threatened species
      lists in conservation, it is imperative that all countries use the same
      categorization system.

PMID- 16909656
TI  - Formation of social acceptability judgments and their implications for management
      of rare and little-known species.
AB  - Effective policies for management of rare and little-known species (RLKS) must be
      not only scientifically valid and cost-effective but also consistent with
      prevailing social beliefs and values. Limited public awareness of RLKS, however
      constrains efforts to frame such policies. Lacking public support, resistance to
      RLKS programs is likely, particularly when other uses and values are affected.
      The challenge lies in understanding how public judgments are formed, sustained,
      and altered. Although the lack of public support often is attributed to
      inadequate understanding of the scientific bases for policies, research indicates
      that judgments derive from a complex, albeit poorly understood, suite of factors,
      including context, trust, esthetics, and personal history. Steps that can enhance
      public understanding of RLKS management include (1) clarifying the rationale and
      impacts of policies on the species, (2) specifying the contextual setting, (3)
      outlining specific actions to be taken, and (4) identifying when and where
      policies will be employed. Failure to foster understanding and support will leave
      management dominated by conflict and continued species loss.

PMID- 16909657
TI  - Inbreeding and endangered species management: is New Zealand out of step with the
      rest of the world?
AB  - There is growing evidence that inbreeding can negatively affect small, isolated
      populations. This contrasts with the perception in New Zealand, where it has been
      claimed that native birds are less affected by inbreeding depression than
      threatened species from continental regions. It has been argued that New
      Zealand's terrestrial birds have had a long history of small population size with
      frequent inbreeding and that this has 'purged" deleterious alleles. The rapid
      recovery of many tiny and inbred populations after introduced predators have been
      controlled, and without input from more genetically diverse populations, has
      further supported the view that inbreeding is not a problem. This has led to a
      general neglect of inbreeding as a factor in recovery programs for highly
      endangered species such as the Black Robin (Petroica traversi) and Kakapo
      (Strigops habroptilis). We examined the reasons for this situation and review the
      New Zealand evidence for genetic purging. Complete purging of the genetic load
      and elimination of inbreeding depression are unlikely to occur in natural
      populations, although partial purging may be more likely where small populations
      have become inbred over an extended period of time, such as on small isolated
      islands. Recent molecular data are consistent with the view that island endemics,
      including New Zealand's threatened birds, have low genetic variation and hence
      have possibly gone through longer periods of inbreeding than threatened species
      from continental regions. Nevertheless, results from recent field studies in New
      Zealand indicate that, despite the opportunity for purging, inbreeding depression
      is evident in many threatened species. Although inbreeding depression has not
      prevented some populations from recovering from severe bottlenecks, the long-term
      consequences of inbreeding and small population size--the loss of genetic
      variation--are potentially much more insidious. The degrees to which genetic
      factors reduce population viability generally remain unquantified in New Zealand.
      Although minimizing ecological risks (e.g., preventing reinvasion of islands by
      mammalian predators) will continue to receive high priority in New Zealand
      because of their much larger impacts, we advocate that genetic considerations be
      better integrated into recovery plans.

PMID- 16909658
TI  - Protected areas and prospects for endangered species conservation in Canada.
AB  - Reserve networks figure prominently in conservation strategies that aim to reduce
      extinction rates. We tested the effectiveness of the current reserve network at
      protecting species at risk in Canada, where relatively extensive wilderness areas
      remain. We compared numbers of terrestrial species at risk included in existing
      reserves to randomly generated networks with the same total area and number of
      reserves. Existing reserve networks rarely performed better than randomly
      selected areas and several included fewer endangered species than expected by
      chance, particularly in the most biologically imperiled regions. The extent of
      protected area and density of species at risk were unrelated at either broad
      (countrywide) or finer spatial scales (50 x 50 km grids), although there was a
      tendency for the most threatened regions of the country to have few or no
      protected areas (1.5% of areas with >30 endangered species were in reserves).
      Although reserves will play a useful role in conserving endangered species that
      occur within them, reducing extinction rates in a region with much of the world's
      remaining wilderness will require integrating conservation strategies with
      agricultural and urban land-use plans outside formally protected areas.

PMID- 16909659
TI  - Gaps and mismatches between global conservation priorities and spending.
AB  - Several international conservation organizations have recently produced global
      priority maps to guide conservation activities and spending in their own and
      other conservation organizations. Surprisingly, it is not possible to directly
      evaluate the relationship between priorities and spending within a given
      organization because none of the organizations with global priority models tracks
      how they spend their money relative to their priorities. We were able, however to
      evaluate the spending patterns of five other large biodiversity conservation
      organizations without their own published global priority models and investigate
      the potential influence of priority models on this spending. On average,
      countries with priority areas received greater conservation investment; global
      prioritization systems, however explained between only 2 and 32% of the U.S.
      dollars 1.5 billion spent in 2002, depending on whether the United States was
      removed from analyses and whether conservation spending was adjusted by the per
      capita gross domestic product within each country. We also found little overlap
      in the spending patterns of the five conservation organizations evaluated,
      suggesting that informal coordination or segregation of effort may be occurring.
      Our results also highlight a number of potential gaps and mismatches in how
      limited conservation funds are spent and provide the first audit of global
      conservation spending patterns. More explicit presentation of conservation
      priorities by organizations currently withoutpriority models and better tracking
      of spending by those with published priorities are clearly needed to help make
      future conservation activities as efficient as possible.

PMID- 16909660
TI  - Inhibition of Amazon deforestation and fire by parks and indigenous lands.
AB  - Conservation scientists generally agree that many types of protected areas will
      be needed to protect tropical forests. But little is known of the comparative
      performance of inhabited and uninhabited reserves in slowing the most extreme
      form of forest disturbance: conversion to agriculture. We used satellite-based
      maps of land cover and fire occurrence in the Brazilian Amazon to compare the
      performance of large (> 10,000 ha) uninhabited (parks) and inhabited (indigenous
      lands, extractive reserves, and national forests) reserves. Reserves
      significantly reduced both deforestation and fire. Deforestation was 1.7
      (extractive reserves) to 20 (parks) times higher along the outside versus the
      inside of the reserve perimeters and fire occurrence was 4 (indigenous lands) to
      9 (national forests) times higher. No strong difference in the inhibition of
      deforestation (p = 0. 11) or fire (p = 0.34) was found between parks and
      indigenous lands. However, uninhabited reserves tended to be located away from
      areas of high deforestation and burning rates. In contrast, indigenous lands were
      often created in response to frontier expansion, and many prevented deforestation
      completely despite high rates of deforestation along their boundaries. The
      inhibitory effect of indigenous lands on deforestation was strong after centuries
      of contact with the national society and was not correlated with indigenous
      population density. Indigenous lands occupy one-fifth of the Brazilian Amazon
      five times the area under protection in parks--and are currently the most
      important barrier to Amazon deforestation. As the protected-area network expands
      from 36% to 41% of the Brazilian Amazon over the coming years, the greatest
      challenge will be successful reserve implementation in high-risk areas of
      frontier expansion as indigenous lands are strengthened. This success will depend
      on a broad base of political support.

PMID- 16909661
TI  - Cost-efficiency of decaying wood as a surrogate for overall species richness in
      boreal forests.
AB  - Decaying wood is one of the most important elements for species richness in
      boreal forests. We tested how well reserve selection based on the amount and
      quality of decaying wood results in a representation of four ecologically
      different taxa (beetles, birds, wood-inhabiting fungi, and vascular plants). We
      also compared the cost-efficiency of the use of dead-wood indicators with
      comprehensive species inventory. Our database included 32 seminatural old-forest
      stands located in northern Finland. Decaying wood was a relatively good indicator
      of saproxylic species but not overall species richness. Even though dead wood did
      not reflect accurately overall species richness, our results indicated that the
      use of decaying wood as an indicator in site selection was more cost-efficient
      than using information from large-scale species inventories. Thus, decaying wood
      is a valuable surrogate for species richness, but other cost-efficient indicators
      that reflect the requirements of those species which are not dependent on
      decaying wood should be identified.

PMID- 16909662
TI  - A nationwide assessment of the biodiversity value of Uganda's important bird
      areas network.
AB  - BirdLife International's Important Bird Areas (IBA) program is the most developed
      global system for identifying sites of conservation priority There have been few
      assessments, however, of the conservation value of IBAs for nonavian taxa. We
      combined past data with extensive new survey results for Uganda's IBAs in the
      most comprehensive assessment to date of the wider biodiversity value of a
      tropical country's IBA network. The combined data set included more than 35,000
      site x species records for birds, butterflies, and woody plants at 86 Ugandan
      sites (23,400 km2), including 29 of the country's 30 IBAs, with data on
      additional taxa for many sites. Uganda's IBAs contained at least 70% of the
      country's butterfly and woody plant species, 86% of its dragonflies and 97% of
      its birds. They also included 21 of Uganda's 22 major vegetation types. For
      butterflies, dragonflies, and some families of plants assessed, species of high
      conservation concern were w'ell represented (less so for the latter). The IBAs
      successfully represented wider biodiversity largely because many have distinctive
      avifaunas and, as shown by high cross-taxon congruence in complementarity, such
      sites tended to be distinctive for other groups too. Cross-taxon congruence in
      overall species richness was weaker and mainly associated with differences in
      site size. When compared with alternative sets of sites selected using
      complementarity-based, area-based, or random site-selection algorithms, the IBA
      network was efficient in terms of the number of sites required to represent
      species but inefficient in terms of total area. This was mainly because IBA
      selection considers factors other than area, however which probably improves both
      the cost-effectiveness of the network and the persistence of represented species.

PMID- 16909663
TI  - A spatially explicit decision support model for restoration of forest bird
      habitat.
AB  - The historical area of bottomland hardwood forest in the Mississippi Alluvial
      Valley has been reduced by >75%. Agricultural production was the primary
      motivator for deforestation; hence, clearing deliberately targeted higher and
      drier sites. Remaining forests are highly fragmented and hydrologically altered,
      with larger forest fragments subject to greater inundation, which has negatively
      affected many forest bird populations. We developed a spatially explicit decision
      support model, based on a Partners in Flight plan for forest bird conservation,
      that prioritizes forest restoration to reduce forest fragmentation and increase
      the area of forest core (interior forest >1 km from "hostile" edge). Our primary
      objective was to increase the number of forest patches that harbor >2000 ha of
      forest core, but we also sought to increase the number and area of forest cores
      >5000 ha. Concurrently, we targeted restoration within local (320 km2) landscapes
      to achieve > or =60% forest cover Finally, we emphasized restoration of higher
      elevation bottomland hardwood forests in areas where restoration would not
      increase forest fragmentation. Reforestation of 10% of restorable land in the
      Mississippi Alluvial Valley (approximately 880,000 ha) targeted at priorities
      established by this decision support model resulted in approximately 824,000 ha
      of new forest core. This is more than 32 times the amount of core forest added
      through reforestation of randomly located fields (approximately 25,000 ha). The
      total area of forest core (1.6 million ha) that resulted from targeted
      restoration exceeded habitat objectives identified in the Partners in Flight Bird
      Conservation Plan and approached the area of forest core present in the 1950s.

PMID- 16909664
TI  - Avian community response to lowland tropical rainforest isolation: 40 years of
      change at La Selva Biological Station, Costa Rica.
AB  - Since 1960, most of the forest surrounding the La Selva Biological Station, an
      intensively studied tropical research facility in Costa Rica, has been converted
      to agricultural uses. We used quantitative censuses and analysis of previously
      published categorical abundances to assess changes in the bird community, and we
      evaluated potential causes of species-specific changes by assessing their
      association with habitat, diet, participation in mixed-species flocks, and nest
      type. Approximately the same percentage of species increased as decreased in
      abundance from 1960 to 1999 (10-20% of all species, depending on method of
      assessment). Diet was the single most important trait associated with declining
      species. At least 50% of the species that declined have insectivorous diets. Use
      of forest habitat and participation in mixed-species flocks were also significant
      factors associated with declines, but nest type was unrelated to change in
      abundance. The species that increased in abundance tended to occur in open
      habitats and have omnivorous diets. These results reinforce the importance of
      several population risk factors associated with tropical understory insectivory
      and mixed-species flocking: patchy spatial distribution, low population density,
      large home range, and dietary specialization. La Selva's protected area (1611
      ha), despite a forested connection on one boundary with a higher elevation
      national park, is apparently too small to maintain at least one major guild
      (understory insectivores). This first quantitative assessment of bird community
      change at La Selva highlights the need to intensify study of the mechanisms and
      consequences of biological diversity change in tropical forest fragments.

PMID- 16909665
TI  - A 16-year study of forest disturbance and understory bird community structure and
      composition in Tanzania.
AB  - I compared understory bird community structure and composition among primary,
      slightly disturbed, and moderately disturbed forest in the East Usambara
      Mountains in Tanzania. Comparisons were conducted at two spatiotemporal scales:
      short term, conducted in 1999 and 2000, in which treatments (disturbance levels)
      were replicated, and long term, conducted from 1989-2004 along the same
      disturbance gradient of a subset of the short-term sites. I used capture
      recapture models to assess the probability of detection and estimate species
      richness and population growth rates. The probability of detection of species did
      not vary significantly among disturbance levels but did vary significantly among
      species. Over the short- and long-term surveys, estimated species richness did
      not vary significantly among disturbance levels. Temporal variability in
      estimated species richness and the relative abundance of guilds did vary
      significantly among disturbance levels yet was contingent on survey length. The
      coefficient of variation in species richness over the short-term survey was <5%
      across all disturbance levels, whereas over the long-term survey it was 35% in
      slightly disturbed forest, 11% in moderately disturbed forest, and 0% in primary
      forest. In the short-term survey, zero of seven feeding guilds varied
      significantly in relative abundance among disturbance levels, whereas over the
      long-term survey four of seven (57%) feeding guilds did so. Terrestrial
      insectivores were most adversely affected by forest disturbance. Population
      growth rates (lamda) between 1989 and 2004 for the more common species of
      terrestrial insectivores did not vary significantly among disturbance levels and
      for these species were significantly < or = 1.00, indicating the recovery time
      for terrestrial insectivores in slightly and moderately disturbed forest is very
      long. These results illustrate the importance of long-term studies in assessing
      ecological impacts of forest disturbance and the importance of protecting primary
      forest in the Eastern Arc Mountains.

PMID- 16909666
TI  - An experimental test of matrix permeability and corridor use by an endemic
      understory bird.
AB  - Because of widespread habitat fragmentation, maintenance of landscape
      connectivity has become a major focus of conservation planning, but empirical
      tests of animal movement in fragmented landscapes remain scarce. We conducted a
      translocation experiment to test the relative permeability of three landscape
      elements (open habitat, shrubby secondary vegetation, and wooded corridors) to
      movement by the Chucao Tapaculo (Scelorchilus rubecula), a forest understory bird
      endemic to South American temperate rainforest. Forty-one radio-tagged subjects
      were translocated (individually) to three landscape treatments consisting of
      small release patches that were either entirely surrounded by open habitat
      (pasture), entirely surrounded by dense shrubs, or linked to other patches by
      wooded corridors that were otherwise surrounded by open matrix. The number of
      days subjects remained in release patches before dispersal (a measure of habitat
      resistance) was significantly longer for patches surrounded by open habitat than
      for patches adjoining corridors or surrounded by dense shrubs. These results
      indicate that open habitat significantly constrains Chucao dispersal, in accord
      with expectation, but dispersal occurs equally well through wooded corridors and
      shrub-dominated matrix. Thus, corridor protection or restoration and management
      of vegetation in the matrix (to encourage animal movement) may be equally
      feasible alternatives for maintaining connectivity.

PMID- 16909667
TI  - Habituation of adult Magellanic penguins to human visitation as expressed through
      behavior and corticosterone secretion.
AB  - Ecotourism is increasing worldwide; hence, it is important to know how wildlife
      are affected behaviorally and physiologically by human visitation. We studied the
      effects of human visitation on the Magellanic Penguins (Spheniscus magellanicus)
      at Punta Tombo, Argentina, by monitoring changes in defensive head turns and
      plasma corticosterone (a hormone secreted in response to stress) for penguins
      with and without a history of tourist visitation. Habituation to human visitation
      was rapid. In penguins with no previous exposure to tourists, the number of
      defensive head turns and level of plasma corticosterone decreased significantly
      within 5 days of one 15-minute visit/day. Penguins living in tourist-visited and
      undisturbed areas secreted more corticosterone when captured and restrained than
      penguins visited by a person. Penguins in tourist areas, however did not show as
      strong a corticosterone response to capture and restraint as did penguins in
      areas without tourists. This difference was due to a decreased capability of the
      adrenocortical tissue to secrete corticosterone in tourist-visited birds.
      Although our data show no direct negative effects of tourism on Magellanic
      Penguins at Punta Tombo, consequences of a modification of physiological
      capabilities (e.g., adrenocortical function) may not become apparent until much
      later in life. The physiological differences between tourist-visited and
      undisturbed groups of Magellanic Penguins emphasize the importance of monitoring
      the effects of anthropogenic disturbances on wildlife at multiple levels.

PMID- 16909668
TI  - Effectiveness of a regional corridor in connecting two Florida black bear
      populations.
AB  - Corridors may mitigate the adverse effects of habitat fragmentation by restoring
      or maintaining connectivity between disjunct populations. The efficacy of
      corridors for large carnivores, however has rarely been evaluated objectively. We
      used noninvasive sampling, microsatellite analysis, and population assignment
      tests to evaluate the effectiveness of a regional corridor in connecting two
      Florida black bear (Ursus americanus floridanus) populations (Osceola and Ocala).
      Bear movement was predominantly unidirectional, with a limited mixing of
      individuals from the two populations in one area of the corridor We also
      documented bears in Osceola that were genetically assigned to Ocala and bears in
      Osceola that may be offspring from an Osceola-Ocala mating. Our results indicate
      that the Osceola-Ocala corridor is functional and provides a conduit for gene
      flow between these populations. Human development, however may hinder the use of
      the Osceola-Ocala corridor by bears. The noninvasive sampling and genetic methods
      we used provide a means of evaluating corridor effectiveness that can help
      identify linkages necessary for maintaining metapopulation structure and
      population viability.

PMID- 16909669
TI  - Bycatch of marine mammals in U.S. and global fisheries.
AB  - Fisheries bycatch poses a significant threat to many populations of marine
      mammals, but there are few published estimates of the magnitude of these catches.
      We estimated marine mammal bycatch in U.S. fisheries from 1990 to 1999 with data
      taken from the stock assessment reports required by the U.S. Marine Mammal
      Protection Act. The mean annual bycatch of marine mammals during this period was
      6215 +/- 448 (SE). Bycatch of cetaceans and pinnipeds occurred in similar
      numbers. Most cetacean (84%) and pinniped (98%) bycatch occurred in gill-net
      fisheries. Marine mammal bycatch declined significantly over the decade,
      primarily because of a reduction in the bycatch of cetaceans. Total marine mammal
      bycatch was significantly lower after the implementation of take reduction
      measures in the latter half of the decade. We derived a crude first estimate of
      marine mammal bycatch in the world's fisheries by expanding U.S. bycatch with
      data on fleet composition from the Food and Agriculture Organization. The global
      bycatch of marine mammals is in the hundreds of thousands. Bycatch is likely to
      have significant demographic effects on many populations of marine mammals.
      Better data are urgently needed to fully understand the impact of these
      interactions.

PMID- 16909670
TI  - Differences in the umbrella effects of African amphibians and mammals based on
      two estimators of the area of occupancy.
AB  - Conservation organizations are collecting large-scale data regarding distribution
      and threats to vertebrate taxa. These data sets will enable planners to
      systematically identify large-scale conservation priorities; however, they will
      cover only a tiny proportion of living organisms. Therefore, it is essential to
      investigate to what extent the areas selected for conservation actions can
      provide protection for other species. We analyzed the umbrella effect between
      amphibians and mammals across mainland Africa. We built habitat suitability
      models within the geographic ranges of 1654 species, based on data collected in
      the framework of the World Conservation Union (IUCN) Global Amphibian Assessment
      and IUCN Global Mammal Assessment. We applied systematic reserve selection
      algorithms to two sets of estimators of the area of occupancy of amphibians and
      mammals (geographic ranges and estimated suitable areas) and thus selected four
      reserve systems. We then quantified the protection that each of the four systems
      provided for amphibians and mammals. Reserves selected for amphibians and mammals
      were comparable in area, with the former concentrated in the Afrotropical region
      and the latter more evenly dispersed. Mammal reserves left fewer gaps in species
      coverage among amphibians than the reverse, but amphibian reserves included a
      larger proportion of each mammal's area of occupancy than the reverse. For both
      taxa, setting reserves to include estimated suitable areas instead of ranges
      resulted in the clustering of reserves in the tropics. Furthermore, it
      efficiently protected hidden gaps (species with unsuitable portions of their
      range inside protected areas) in the other taxon and included a higher proportion
      of the area of occupancy of the other taxon. Overall, amphibians and mammals in
      Africa acted as an umbrella for a high proportion of species in the other taxon.
      Focusing on estimated suitable areas instead of ranges improved the umbrella
      effect of both taxa.

PMID- 16909671
TI  - Effects of introduced salmonids on a montane population of Iberian frogs.
AB  - Amphibians are declining worldwide because of multiple factors, including human
      mediated introduction of fishes into naturally fishless areas. Although several
      studies have focused on the effect of exotic fishes on native amphibians breeding
      in ponds or lakes, little is known about their effects on stream-breeding
      species. We studied the effects of introductions of native brown trout (Salmo
      trutta) and exotic brook trout (Salvelinus fontinalis) on the stream-breeding,
      endemic Iberian frog (Rana iberica) in a protected area in central Spain. We
      assessed occurrence patterns of tadpoles and salmonids and compared habitat use
      of the three species. We also determined experimentally whether chemical cues
      from salmonids elicited antipredator behavior in tadpoles. Finally, we assessed
      the relative influence of tadpole habitat preferences, differences in salmonid
      species, and invasion geography on tadpole occurrence. Despite widely overlapping
      habitat preferences, tadpoles and trout did not coexist, with the former
      restricted to fishless habitats. Tadpoles detected chemical cues from both trout
      species and reacted by decreasing their activity, although the response toward
      the native brown trout was stronger The residual distribution of Iberian frogs in
      Penalara is better explained by the geography of fish invasions than by the fish
      species involved. Measures such as fish extirpation from certain areas, aimed at
      recovering lost habitat and improving connectivity among remaining populations of
      Iberian frogs, seem critical for the species' long-term survival in central
      Spain.

PMID- 16909672
TI  - The interplay between climate variability and density dependence in the
      population viability of Chinook salmon.
AB  - The viability of populations is influenced by driving forces such as density
      dependence and climate variability, but most population viability analyses (PVAs)
      ignore these factors because of data limitations. Additionally, simplified PVAs
      produce limited measures of population viability such as annual population growth
      rate (lamda) or extinction risk. Here we developed a "mechanistic" PVA of
      threatened Chinook salmon (Oncorhynchus tshawytscha) in which, based on 40 years
      of detailed data, we related freshwater recruitment of juveniles to density of
      spawners, and third-year survival in the ocean to monthly indices of broad-scale
      ocean and climate conditions. Including climate variability in the model produced
      important effects: estimated population viability was very sensitive to
      assumptions of future climate conditions and the autocorrelation contained in the
      climate signal increased mean population abundance while increasing probability
      of quasi extinction. Because of the presence of density dependence in the model,
      however we could not distinguish among alternative climate scenarios through mean
      lamda values, emphasizing the importance of considering multiple measures to
      elucidate population viability. Our sensitivity analyses demonstrated that the
      importance of particular parameters varied across models and depended on which
      viability measure was the response variable. The density-dependent parameter
      associated with freshwater recruitment was consistently the most important,
      regardless of viability measure, suggesting that increasing juvenile carrying
      capacity is important for recovery.

PMID- 16909673
TI  - Identification of shark species composition and proportion in the Hong Kong shark
      fin market based on molecular genetics and trade records.
AB  - The burgeoning and largely unregulated trade in shark fins represents one of the
      most serious threats to shark populations worldwide. In Hong Kong, the world's
      largest shark fin market, fins are classified by traders into Chinese-name
      categories on the basis of market value, but the relationship between market
      category and shark species is unclear preventing identification of species that
      are the most heavily traded. To delineate these relationships, we designed a
      sampling strategy for collecting statistically sufficient numbers of fins from
      traders and categories under conditions of limited market access because of
      heightened trader sensitivities. Based on information from traders and
      morphological inspection, we hypothesized matches between market names and shark
      taxa for fins within 11 common trade categories. These hypotheses were tested
      using DNA-based species identification techniques to determine the concordance
      between market category and species. Only 14 species made up approximately 40% of
      the auctioned fin weight. The proportion of samples confirming the hypothesized
      match, or concordance, varied from 0.64 to 1 across the market categories. We
      incorporated the concordance information and available market auction records for
      these categories into stochastic models to estimate the contribution of each
      taxon by weight to the fin trade. Auctioned fin weight was dominated by the blue
      shark (Prionace glauca), which was 17% of the overall market. Other taxa,
      including the shortfin mako (Isurus oxyrinchus), silky (Carcharhinus
      falciformis), sandbar (C. obscurus), bull (C. leucas), hammerhead (Sphyrna spp.),
      and thresher (Alopias spp.), were at least 2-6% of the trade. Our approach to
      marketplace monitoring of wildlife products isparticularly applicable to
      situations in which quantitative data at the source of resource extraction are
      sparse and large-scale genetic testing is limited by budgetary or other market
      access constraints.

PMID- 16909674
TI  - Habitat fragmentation effects on trophic processes of insect-plant food webs.
AB  - Habitat fragmentation is the transformation of once-extensive landscapes into
      smaller isolated remnants surrounded by new types of habitat. There is ample
      evidence of impoverished biodiversity as a consequence of habitat fragmentation,
      but its most profound effects may actually result from functional changes in
      ecological processes such as trophic interactions. We studied the trophic
      processes of herbivory and parasitism in insect-plant food webs composed of
      hundreds of species in a fragmented woodland landscape. We recorded all plant
      species, collected mined leaves, and reared leafminers and parasitoids from 19
      woodland remnants. Herbivory and parasitism rates were then analyzed in relation
      to woodland size and edge or interior location. Herbivory by leaf-mining insects
      and their overall parasitism rates decreased as woodland remnants became smaller
      For each remnant the intensity of both processes differed between edge and
      interior Our results provide novel evidence of the magnitude of habitat
      fragmentation effects, showing they can be so pervasive as to affect trophic
      processes of highly complex food webs and suggesting a response associated with
      trophic specialization of the involved organisms as much as with their trophic
      level.

PMID- 16909675
TI  - Using population viability analysis to predict the effects of climate change on
      the extinction risk of an endangered limestone endemic shrub, Arizona cliffrose.
AB  - The threat of global warming to rare species is a growing concern, yet few
      studies have predicted its effects on rare populations. Using demographic data
      gathered in both drought and nondrought years between 1996-2003 in central
      Arizona upper Sonoran Desert, we modeled population viability for the federally
      endangered Purshia subintegra (Kearney) Henrickson (Arizona cliffrose). We used
      deterministic matrix projection models and stochastic models simulating weather
      conditions during our study, given historical weather variation and under
      scenarios of increased aridity. Our models suggest that the P. subintegra
      population in Verde Valley is slowly declining and will be at greater risk of
      extinction with increased aridity. Across patches at a fine spatial scale,
      demographic performance was associated with environmental factors. Moist sites
      (patches with the highest soil moisture, lowest sand content, and most northern
      aspects) had the highest densities, highest seedling recruitment, and highest
      risk of extinction over the shortest time span. Extinction risk in moist sites
      was exacerbated by higher variance in recruitment and mortality. Dry sites had
      higher cumulative adult survival and lower extinction risk but negative growth
      rates. Steps necessary for the conservation of the species include introductions
      at more northern latitudes and in situ manipulations to enhance seedling
      recruitment and plant survival. We demonstrate that fine spatial-scale modeling
      is necessary to predict where patches with highest extinction risk or potential
      refugia for rare species may occur Because current climate projections for the
      21st century imply range shifts at rates of 300 to 500 km/century, which are
      beyond even exceptional examples of shifts in the fossil record of 100-150 km, it
      is likely that preservation of many rare species will require human intervention
      and a long-term commitment. Global warming conditions are likely to reduce the
      carrying capacity of many rare species' habitats.

PMID- 16909676
TI  - Relative contribution of inbreeding depression and eroded adaptive diversity to
      extinction risk in small populations of shore campion.
AB  - To study the relative importance of inbreeding depression and the loss of
      adaptive diversity in determining the extinction risk of small populations, we
      carried out an experiment in which we crossed and self-fertilized founder plants
      from a single, large population of shore campion (Silene littorea Brot.). We used
      the seeds these plants produced to colonize 18 new locations within the
      distribution area of the species. The reintroduced populations were of three
      kinds: inbred and genetically homogeneous, each made up of selfed seed from a
      single plant; inbred and mixed, made up of a mixture of selfed seeds from all
      founder plants; and outbred and mixed, made up of a mixture of seeds obtained in
      outcrosses between the founders. We compared the inbred homogeneous populations
      with the inbred mixed to measure the effect of genetic diversity among
      individuals and the inbred mixed with the outbred mixed to measure the effect of
      inbreeding. Reintroduction success was seriously limited by inbreeding, whereas
      it was not affected by genetic diversity. This observation and the nonsignificant
      interaction between family and reintroduction location for individual plant
      characters suggest that the fixation of overall deleterious genes causing
      inbreeding depression posed a more serious threat to the short-term survival of
      the populations than the loss of genes involved in genotype and environment
      interactions. Thus, reintroduction success was related to adaptive diversity.
      Preventing such fixation might be the most important consideration in the genetic
      management and conservation of shore campion populations.

PMID- 16909677
TI  - Species imperilment and spatial patterns of development in the United States.
AB  - Conservation biologists and others hypothesize that humankind's "ecological
      footprint" is affected not only by the sheer intensity of human activity but also
      by its spatial arrangement. We used a multivariate statistical model and state
      level data to evaluate correlations between species imperilment and the level and
      spatial distribution of human settlement and infrastructure development in the
      United States. The level of human activity--measured by the number of people and
      households, incidence of roads, and intensity of nighttime lights--was
      significantly correlated with the ecological imperilment of species. Our
      regression models consistently showed that a 1% increase in the level of human
      activity across the United States was associated with about a 0.25% increase in
      the proportion of plant and animal species considered at risk of extinction by
      The Nature Conservancy. The distribution of human activity did not affect species
      imperilment. Our results point to rising levels of human activity--and not some
      particular (e.g., sprawling) distribution of human activity--as the most relevant
      anthropogenic factor explaining biodiversity loss in the United States.

PMID- 16909678
TI  - Insect extinctions and insect survival.

PMID- 16909679
TI  - Parks and people: assessing the human welfare effects of establishing protected
      areas for biodiversity conservation.

PMID- 16909680
TI  - Conservation, human rights, and poverty reduction.

PMID- 16909681
TI  - Extirpating the agriculture versus conservation dichotomy.

PMID- 16909682
TI  - [Hypertriglyceridemia].

PMID- 16909683
TI  - [MALT-lymphoma].
AB  - Gastric lymphoma is most frequently an extranodal marginal zone-B-cell-lymphoma
      of mucosa-associated lymphoid tissue (MALT). The diagnosis is established by
      biopsy of the tumor. Computed-tomography, endosonography and recently capsule
      endoscopy are used for staging. It is a relative new finding that MALT-lymphomas
      of the stomach are induced by Helicobacter pylori. A side-effect-poor
      breakthrough has been achieved by eradication of this bacterium with antibiotics.
      Refractory cases are amenable to radiotherapy, chemotherapy or surgical
      resection. The rarer aggressive lymphomas of the stomach are treated primarily by
      chemotherapy and radiotherapy. For both entities a further improvement may be
      achieved in ongoing prospective clinical trials by addition of the monoclonal
      antibody rituximab, which targets CD20 on lymphoma cells.

PMID- 16909684
TI  - [Achalasia--early diagnosis and treatment options].
AB  - Achalasia is a rare motility disorder of the distal esophagus, showing reduced or
      absent swallow induced relaxation of the lower esophageal sphincter region. The
      onset of the disease can be very slow and correct diagnosis might be delayed over
      years. Using exact medical history, upper GI endoscopy and barium swallow X-ray
      the achalasia can be suspected and can be confirmed by esophageal manometry.
      Other especially malignant diseases, which can imitate the clinical symptoms,
      have to be ruled out. Pneumatic balloon dilatation is therapy of first choice in
      achalasia. Especially in younger patients laparoscopic fundoplication with
      subsequent antireflux procedure should be offered early in the therapeutic
      algorithm when dilatation therapy fails. Medical therapy or intrasphincteric
      injection of botulinum toxin is only an alternative treatment for high risk
      patients, treatment failures or residual symptoms.

PMID- 16909685
TI  - [Diagnosis of gastroesophageal reflux disease and dyspepsia].
AB  - Prerequisite in the diagnosis of heartburn and dyspepsia is a careful medical
      history which has to take into account both the differential diagnosis as well as
      alarm symptoms necessitating immediate and more extensive diagnostic procedures.
      The by far most prevalent diseases are gastroesophageal reflux disease (GERD),
      functional dyspepsia and peptic ulcers (today overwhelmingly due to ulcerogenic
      drugs but less common to Helicobacter pylori). In the further diagnostic
      evaluation, endoscopy is the most valuable tool revealing GERD as the dominating
      lesion whereas ulcers become much less frequent and malignancies are rare under
      50 years of age; thus, empiric therapy is an attractive strategy in such younger
      population. Ultrasound investigations are recommended predominantly in cases with
      suspected biliary disease but not in general. Apart from basic laboratory blood
      tests further diagnostic procedures do not play a role in the primary evaluation
      in this setting.

PMID- 16909686
TI  - [Gastroesophageal reflux disease and dyspepsia--drug therapy].
AB  - Proton pump inhibitors (PPI) are the antisecretory drugs of choice to manage GERD
      related problems. The therapeutic goal in patients with non erosive reflux
      disease (NERD) and low-grade-GERD is to relieve symptoms, therefore PPI are given
      "on demand". Severe GERD requires long term treatment to heal lesions and to
      prevent relapses and complications. Barrett's esophagus has to be regarded as a
      precancerous lesion, therefore surveillance strategy is required. Functional
      dyspepsia is a common reason for upper gastrointestinal symptoms. If there are no
      alarming symptoms, you can omit endoscopy in younger patients. The treatment is
      empirical and symptom driven. Psychologic therapy is a promising avenue in some
      patients.

PMID- 16909687
TI  - [GERD: endoscopic antireflux therapies].
AB  - A couple of minimally-invasive, endoscopic antireflux procedures have been
      developed during the last years. Beside endoscopic suturing these included
      injection/implantation technique of biopolymers and application of
      radiofrequency. Radiofrequency (Stretta) has proved only a very modest effect,
      while implantation techniques have been abandoned due to lack of long-term
      efficacy (Gatekeeper) or serious side effects (Enteryx). While first generation
      endoluminal suturing techniques (EndoCinch, ESD) demonstrated a proof of
      principle their lack of durability, due to suture loss, led to the development of
      a potentially durable transmural plication technique (Plicator). In a prospective
      randomized, sham-controlled trial the Plicator procedure proved superiority
      concerning reflux symptoms, medication use and esophageal acid exposure (24-h-pH
      metry). While long-term data have to be awaited to draw final conclusions,
      technical improvements will drive innovation in this field.

PMID- 16909688
TI  - [GERD: surgical therapy].
AB  - Proton pump inhibitors (PPIs) are generally accepted as gold standard for
      treatment of gastro-esophageal reflux disease (GERD). Nevertheless, there are
      clear indications for surgical anti-reflux therapy. Principally, laparoscopic
      anti-reflux therapy is an excellent therapeutic alternative in all patients, who
      have objective or subjective problems with long-term PPI therapy. Clear cut proof
      of the symptomatic gastro esophageal reflux (endoscopy, 24 h pH-testing) is an
      absolute prerequisite for surgery. Partial or total laparoscopic fundoplication
      has replaced completely open operative techniques. Treatment of the hiatal hernia
      and the hiatoplasty are integral parts of the operation. Perioperative
      complication rate is low. The long-term results are good. Proper patient
      selection and correct indication for operation are most important in this
      respect.

PMID- 16909689
TI  - Family history and pedigree charting--a simple genetic tool for Indian diabetics.

PMID- 16909690
TI  - Study of inheritance of diabetes mellitus in Western Indian population by
      pedigree analysis.
AB  - OBJECTIVES: To study the inheritance pattern of diabetes mellitus in Western
      Indian population by analysing the pedigree of diabetes patients. METHODS: 3,921
      individuals from 300 families were interviewed for family history in this study,
      out of which 770 were diabetic individuals. Statistical analysis of the data was
      carried out using T-test and Chi-square test. RESULTS: 37% cases of Type 1 DM and
      58% cases of Type 2 DM showed family history of the disease. Of the cases showing
      family history for diabetes, 92% in case of Type 1 DM and 59% in case of Type 2
      DM showed family history of Type 2 DM with a decrease in age of onset in the
      successive generations. Both the parents, when diabetic conferred equal risk of
      inheriting diabetes in offspring. The sex ratio of offspring suffering from
      diabetes was not influenced when only one of the parents was diabetic. However it
      was observed that the male offspring were highly susceptible when both parents
      were diabetic (Chi-square value=4.55 with 1 d.f.). The age of onset of diabetes
      did not show significant correlation with whether one or both the parents were
      diabetic. However, it was noteworthy that in case of familial history of diabetes
      there was a decrease in the age of onset in successive generations. CONCLUSION:
      This study suggests that family history of diabetes results in predisposition to
      early onset of the disease in successive generations and a cluster of genes
      involved in Type 2 DM may show a parental effect for predisposition to Type 1 DM
      in the offspring in this set of Indian population.

PMID- 16909691
TI  - Etiological spectrum of non-traumatic myelopathies: experience from a tertiary
      care centre.
AB  - AIM: This study aimed to identify the clinical and radiological profile of non
      traumatic myelopathies and various etiologies associated with them. MATERIAL AND
      METHODS: Two hundred and four patients of non-traumatic myelopathy were
      prospectively studied in different wards of Sir Sundar Lal Hospital, Institute of
      Medical Sciences, Banaras Hindu University, Varanasi, from September 2002 to
      March2004. Patients underwent a detailed clinical evaluation followed by
      laboratory investigation and neuroimaging studies. RESULTS: Among 204 patients of
      non-traumatic myelopathy, 108 patients presented with paraplegia and 96 patients
      with quadriplegia. Tuberculosis was the commonest cause of compression paraplegia
      in this series and was observed in 42 cases (33.33%) while quadriplegia was seen
      in only 3 cases (2.38%). In the present study, acute transverse myelitis formed
      the major bulk of non-compressive myelopathy. CONCLUSION: Tuberculosis of spine
      was the most common cause of compressive myelopathy and among the non-compressive
      group acute transverse myelitis and SACD were the important etiology.

PMID- 16909692
TI  - Reno-protective effect of N-acetyl cysteine in patients with impaired renal
      function undergoing coronary angiography and interventions.
AB  - BACKGROUND: The increasingly frequent use of contrast enhanced imaging for
      diagnosis or interventions in patients with CAD has generated concern about
      avoidance of contrast induced nephropathy (CIN). Reactive oxygen species have
      been shown to cause CIN. OBJECTIVES: Angiographic contrasts worsen the renal
      function in patients with renal failure. We studied the reno-protective action of
      the antioxidant N-Acetyl cysteine (NAC) in patients undergoing coronary
      procedures. METHODS: Retrospective analysis of 51 patients with elevated serum
      creatinine levels (> or = 15mg%) was done, 24 of whom received NAC prior to the
      procedure(NAC group) and 27 who did not (Non NAC group). NAC was administered in
      a dose of 400 mg twice daily for four doses starting on the day prior to the
      procedure. Both groups of patients were hydrated with 0.45% saline at 1 ml/kg/hr
      for 12 hours prior to and 12 hours following the procedure. Both groups were
      comparable with regard to age, sex, coronary risk profile, myocardial infarction
      history, left ventricular function and the drugs received. Serum urea and
      creatinine were measured on the day prior to and the day following the
      angiographic procedure. RESULTS: Nine out of 51 patients developed more than
      0.5mg% rise in serum creatinine level; 1 in the NAC group and 8 in the non NAC
      group (p<0.05), 24 hours after injection of the contrast medium. In the NAC group
      mean serum creatinine level decreased from 1.94 +/- 0.56 to 1.67 +/- 0.56 and
      blood urea from 47.58 +/- 20 to 41.58 +/- 15.1. In the non NAC group serum
      creatinine increased from 1.75 +/- 0.31 to 1.98 +/- 0.56 and blood urea from
      44.96 +/- 15.5 to 52.85 +/- 20.1 (p<0.05). This corresponds to an increase in
      creatinine clearance from 30ml/min to 35.92ml/min in the NAC group and a decrease
      from 34.42ml/min to 29.87ml/min in the non NAC group. There was no significant
      difference in the levels of sodium and potassium before and after the procedure
      in both the groups. CONCLUSION: We conclude that prophylactit administration of N
      Acetyl Cysteine along with hydration diminishes the incidence of deterioration of
      renal function induced by contrast agents in patients with renal insufficiency
      during coronary angiographic procedures.

PMID- 16909693
TI  - Erythrocyte enzyme abnormalities in leukemias.
AB  - Red cell enzymes were assayed in a total of 67 patient including 24 patients with
      AML (19 relapse, 5 remission), 16 patients with ALL (10 relapse, 6 remission), 22
      patients with CML and 5 patients with blastic CML. Diagnosis of leukemia was
      based on clinical presentation, peripheral blood smear and bone marrow
      examination (as per FAB classification). PK activity was significantly high in
      case of CML and blastic CML (p<0.01). Red cell HK was high in all leukemia
      subtypes. There was no alteration in red cell G6PD. Notably there was no PK
      deficiency in AML or G6PD deficiency in ALL. Activities of G6PD and PK could be
      correlated in cases of CML, AML, (p<0.05) and ALL (p<0.01) i.e. when there was
      increased activity of G6PD, PK activity also tended to be higher. HK activity
      showed a positive correlation with PK and G6PD activity in cases of CML (p<0.05),
      however in acute leukemia there was no such correlation. Alteration of enzyme
      activities among red cells in leukemia occurred only during relapse. At the time
      of remission there has been no significant alteration in any of the enzyme
      activities. It would therefore, appear that enzyme alterations seen in leukemia
      patients is due to abnormal pluripotent stem cell that has given to a leukemia
      cell. The fact that enzyme alterations have primarily occurred at the time of
      relapse would further substantiate that abnormalities of red cell enzymes may be
      the result of a derivation some circulating red cells from the abnormal
      pluripotent stem cell. With the recovery of normal stem cells function during
      remission, enzyme abnormalities tend to become normal.

PMID- 16909694
TI  - Management of echinococcosis.
AB  - Cystic echinococcosis is a zoonosis caused by larval forms of the tapeworm
      Echinococcus granulosus and transmitted by dogs. In humans, the disease is
      characterized by slowly growing cyst commonly occurring in liver and lungs.
      Clinical features of hepatic hydatid cyst are mainly right upper quadrant pain,
      feeling of lump and enlarged tender liver. The cyst may be complicated by
      infection or rupture and may lead to anaphylactic reaction. Ultrasonography
      supported by serology is the main diagnostic modality. Treatment of univesicular
      cyst is predominantly medical or percutaneous. Percutaneous treatment (PAIR) is
      safe and effective and complications are infrequent. For multivesicular and
      complicated cyst surgery remains the mainstay of treatment.

PMID- 16909695
TI  - AIDS dementia complex.

PMID- 16909696
TI  - Neurocysticercosis causing starry sky appearance--a non-ictal manifestation.

PMID- 16909697
TI  - API expert consensus document on management of ischemic heart disease.
AB  - The incidence of coronary artery disease (CAD) has dramatically increased in
      India during the recent years. There are two facets of CAD: stable CAD and
      unstable CAD which includes patients with acute coronary syndrome (unstable
      angina, non-ST elevation myocardial infarction, ST elevation myocardial
      infarction). The treatment of stable CAD (stable angina) includes anti-anginal
      medication, medication to modify atherosclerosis and aggressive treatment of
      causative risk factors. Those patients with stable CAD who have symptoms
      refractory to medical treatment usually require coronary angiography to be
      followed by either percutaneous or surgical revascularization. Percutaneous
      coronary revascularization using drug eluting stents has been a major revolution
      during the last five years for symptomatic relief of angina in symptomatic CAD
      and can be applied to large subsets of patients. Off-pump surgical
      revascularization using arterial grafts is a major advance and bypass surgery
      continues to remain treatment of choice in diabetics with multi-vessel CAD, left
      main CAD and in patients with multivessel disease and impaired ventricles. Acute
      coronary syndromes are usually caused by plaque rupture with resultant thrombus
      and present as unstable angina, non-ST elevation myocardial infarction (NSTEMI)
      and ST-elevation myocardial infarction (STEMI). It is now increasingly realized
      that these patients (particularly the one with high risk) are best managed in
      advanced cardiac care centres with facilities for cardiac catheterization
      laboratory, percutaneous coronary interventions and coronary bypass surgery. In
      both, NSTEMI and STEMI aggressive medical management involving nitrates, ACE
      inhibitors, beta-blockers, dual anti-platelet agents, heparin and statins are
      recommended. High risk patients with NSTE-ACS require use of glycoprotein IIa /
      IIIb inhibitors along with early invasive approach involving coronary
      angiography, angioplasty using drug eluting stent and in some patients bypass
      surgery. Early reperfusion is key to management of patients presenting with
      STEMI. If facilities are available, primary percutaneous coronary intervention
      (angioplasty with stenting) is treatment of choice for patients with STEMI. In
      our country, thrombolysis still remains the most frequently utilized reperfusion
      therapy and all efforts should be devoted to provide this therapy at the
      earliest. All high risk patients with STEMI (including cardiogenic shock) are
      best treated in higher centres and these patients should be promptly transported
      to such centres. Early coronary angiography is recommended for majority of
      patients following thrombolysis for risk stratification and further treatment. In
      acute coronary syndromes there is drift towards early invasive treatment and this
      is reflected in marked increase in cardiac care (catheterization laboratories and
      cardiac surgery centers) facilities throughout India. All patients with CAD
      require life-long supervised treatment which includes medication, control of risk
      factors and lifestyle modification. Avoidance of smoking, heart healthy diet,
      proper exercise, ideal weight management are important for all the patients.
      Statins, ACE inhibitors, beta-blockers, antiplatelet agents have a great role to
      play in treatment and prevention and these drugs should be utilized under medical
      supervision. It is important that the medical profession play an important role
      in critically evaluating the use of diagnostic procedures and therapies as they
      are introduced and tested in the detection and management of cardiac disorders.
      The American College of Cardiology (ACC), American Heart Association (AHA),
      European Society of Cardiology (ESC), Society for Cardiovascular Angiography and
      Interventions (SCAI) and several other societies engage in production of
      guidelines in the area of cardiovascular diseases from time to time. These
      guidelines attempt to define practices that meet the needs of most patients in
      most circumstances. The aim of the guidelines is to improve the patient care. The
      ultimate judgement regarding the care of the particular patient is to be made by
      the clinician / healthcare provider keeping in mind all the circumstances. The
      incidence and prevalence of coronary artery disease (CAD) has increased
      tremendously in India during the last two decades and this change is largely
      attributable to lifestyle changes. There has also been a rapid progress in the
      treatment of CAD with proliferation of specialized cardiac care units, intensive
      care units, cardiac catheterization laboratories and facilities for bypass
      surgery. It is estimated that there are over 400 catheterization laboratories
      currently in India and nearly half of them are located in six major cities. The
      increase in disease and availability of facilities has resulted in a dramatic
      change and the focus is shifting from only medical treatment to invasive
      treatment. This document is an expert consensus document which has been prepared
      by going through the available guidelines and other relevant literature on the
      subject. The experts have performed a formal review of the literature and have
      weighed the strength of evidence for or against a particular therapy as it can be
      applied in Indian scenario. The consensus document deals with the management of
      ischemic heart disease (IHD) under following sections: 1) Stable Angina 2) Non ST
      Elevation Acute Coronary Syndrome (NSTE-ACS) 3) ST Elevation Acute Coronary
      Syndrome (STE-ACS) or Acute Myocardial Infarction (AMI).

PMID- 16909698
TI  - Portal biliopathy.
AB  - A young male with portal venous thrombosis presented with obstructive jaundice,
      due to common bile duct stricture secondary to portal biliopathy.

PMID- 16909699
TI  - Non-hypertensive intracerebral haemorrhage: some interesting observations.
AB  - Hypertension is the commonest cause of intracerebral hemorrhage (ICH) but non
      hypertensive intracerebral hemorrhages (NHICH) are not rare. We report three
      interesting cases of NHICH subsequent to amyloid angiopathy, alcoholic hepatitis
      and amphetamine abuse. They suggest the importance of recognizing these
      conditions and need for urgent specific therapy which may play a vital role in
      therapeutic planning and prevention of ICH.

PMID- 16909700
TI  - Colo-vesical fistula presenting as urinary tract infection.
AB  - We report a 59 years male who presented with urinary tract infection due to a
      colovesical fistula secondary to colonic diverticuli.

PMID- 16909701
TI  - Myocarditis and multiple cerebral and cerebellar infarction following scorpion
      sting.
AB  - An unusual case of scorpion sting followed by multiple cerebral and cerebellar
      watershed infarctions is being reported. Myocarditis, hypotension and
      hypoperfusion infarction is being considered as the possible explanation for this
      pathology. Hypoperfusion leading to parieto-occipital infarction has been
      reported earlier, however cerebellar infarction in this context is extremely
      rare.

PMID- 16909702
TI  - Nocardiosis in a patient with common variable immunodeficiency.
AB  - We report a case of nocardiosis in a 42, years male with common variable
      immunodeficiency syndrome (CVID). He presented with arthritis, subcutaneous
      abscess and pleural effusion. Diagnosis of CVID was made during this
      presentation. Serum IgG, IgA and IgM levels were markedly decreased. Nocardia
      asteroides was cultured from pleural fluid. He was successfully treated with
      intravenous immunoglobulin and cotrimoxazole.

PMID- 16909703
TI  - Nephrocalcinosis in siblings--familial hypomagnesemia, hypercalciuria with
      nephrocalcinosis (FHHNC syndrome).
AB  - Familial Hypomagnesemia, Hypercalciuria with Nephrocalcinosis is a rare autosomal
      recessive inherited disease associated with renal failure. Two girls born of
      consanguineous parentage aged 16 and 17 presented to us with renal failure,
      nephrocalcinosis and bone deformities. On evaluation they were found to have
      hypomagnesemia, hypercalciuria, increased fractional excretion of magnesium,
      hypocitraturia, renal failure and elevated PTH. Their parental screening was
      normal. There were no extra-renal features in them. One sibling had
      nephrolithiasis and the stone analysis revealed calcium phosphate stones. Both
      were treated with sodium bicarbonate, thiazides, calcitriol and calcium
      carbonate. They did not require dialysis during hospital stay. Both of them were
      treated conservatively. They are on regular outpatient follow up. The primary
      defect in this syndrome is impaired paracellular reabsorption of magnesium and
      calcium in the medullary thick ascending limb. Mutations in the PCLN-1gene which
      encodes for the tight junction protein paracellin -1 is identified as the
      underlying genetic defect. Ocular abnormalities and deafness are the commonly
      reported associations. End stage renal failure usually occurs in second to third
      decade. Renal transplantation is the definite treatment.

PMID- 16909704
TI  - Anton Van Leeuwenhoek (1632-1723). Postal stamps issued on Leeuwenhoek-
      Netherland--1937 and Transkei 1982.

PMID- 16909705
TI  - Salt restriction in ascites with cirrhosis of liver: will enhanced salt
      restriction increase longevity?

PMID- 16909706
TI  - Idiopathic clubbing.

PMID- 16909707
TI  - Nascent subspeciality of rheumatology.

PMID- 16909708
TI  - Evidence-based practice in rheumatology.

PMID- 16909709
TI  - Vasculitis--Indian perspective.

PMID- 16909710
TI  - Cytokine network and its manipulation in rheumatoid arthritis.
AB  - Studies of the inflammatory process in the inflamed synovium from rheumatoid
      arthritis patients have shown an intricate network of molecules involved in its
      initiation, perpetuation and regulation trial balances the pro- and anti
      inflammatory process. This system is self-regulating though the action of anti
      inflammatory and pro-inflammatory cytokines cytokine receptor antagonists and
      naturally occurring antibodies cytokines. Inflammatory synovitis in rheumatoid
      arthritis (and possibly in other inflammatory arthritidies) appears to be the
      result of an imbalance in the cytokine network with either an excess production
      of pro-inflammatory cytokines or from inadequacy of the natural anti-inflammatory
      mechanisms. Using this knowledge the newer therapeutic approaches to RA and other
      inflammatory arthritides are being aimed at correcting this imbalance. Monoclonal
      antibodies to INF-alpha (humanised form of this is called infliximab), soluble
      TNF-alpha receptors (etanercept) are already in clinical use and adalimumab
      (humanised TNF-alpha antibody). IL-1Ra is undergoing clinical trials. Other
      promising therapeutic agents that could regulate the cytokine network are in
      various stages of laboratory and clinical evaluation. These studies promise to
      yield therapeutic targets that could dramatically change the way inflammatory
      diseases would he treated in the future. The now established efficacy of
      infliximab and etanercept in inflammatory arthritides could be considered just a
      glimpse of the exciting scenario of the future.

PMID- 16909711
TI  - Systemic lupus erythematosus and pregnancy.

PMID- 16909712
TI  - Long term complications in systemic lupus erythematosus.

PMID- 16909713
TI  - Infection and arthritis.

PMID- 16909714
TI  - Antiphospholipid syndrome--clinical overview.

PMID- 16909715
TI  - Musculoskeletal manifestations of human immunodeficiency virus infection.

PMID- 16909716
TI  - Rheumatic fever--how relevant in India today?

PMID- 16909717
TI  - Advances in therapy of systemic sclerosis.

PMID- 16909718
TI  - Arthroscopy for rheumatologist: opportunities and challenges.

PMID- 16909719
TI  - Sjogren's syndrome--diagnosis and management.

PMID- 16909720
TI  - Rheumatolological emergencies.

PMID- 16909721
TI  - Idiopathic inflammatory myopathies.

PMID- 16909722
TI  - The Spanish influenza: a tale from my grandmother's day.

PMID- 16909723
TI  - [Is a healing sleep possible in intensive care?].

PMID- 16909724
TI  - [What do health professionals think about parents' participation in care for
      children?].
AB  - This research report concerns a pilot study carried out in Canada and Belgium
      concerning the beliefs and attitudes of healthcare professionals--doctors and
      nurses--regarding parents' participation in ambulatory care for their children.
      The professionals surveyed see many advantages in such participation, including
      less stress for parents and children, but they also see some obstacles, most of
      them related to the parents themselves and the hospital environment.

PMID- 16909725
TI  - [The challenges of Helene Durocher. Interview by Laurette Therrien].

PMID- 16909726
TI  - [The central catheter inserted peripherally].

PMID- 16909727
TI  - [IChoosing the best disposable vascular access device].

PMID- 16909729
TI  - [Hope and end of life: a paradox that is a source of moral tension].

PMID- 16909730
TI  - Heat stroke: managing a tropical continuum.

PMID- 16909728
TI  - [An unsuspected killer: child drowning in the domestic milieu].

PMID- 16909731
TI  - Outcome predictors for non-invasive positive pressure ventilation in acute
      respiratory failure.
AB  - BACKGROUND: Noninvasive positive pressure ventilation (NIPPV) has emerged as a
      significant advancement in the management of acute respiratory failure.
      OBJECTIVE: To identify factors, based on clinical and laboratory parameters, for
      predicting the outcome of NIPPV in patients with acute respiratory failure.
      MATERIALS AND METHODS: Fifty patients were included in the study. Inclusion
      criteria were RR>30 breaths/ min, PaO2<60mmHg, PaO2/FiO2<300, pCO2< or = 45mmHg
      and signs of increased work of breathing. Baseline clinical parameters and
      arterial blood gas (ABG) were recorded before initiating NIPPV. Clinical
      parameters including heart rate, respiratory rate, oxygen saturation and ABG was
      revaluated at 1, 4, 12, 24 hrs after initiation of NIPPV. Change in these
      parameters and need for intubation was evaluated. RESULTS: Of the 50 patients, 37
      (74%) showed clinical and ABG improvement. Out of 13 (26%) patients who failed to
      respond, 7 (52%) needed endotracheal intubation within 1 hr. There was
      significant improvement in clinical and ABG parameters within 1st hr in success
      group and these parameters continues to improve even after 4 hrs of NIPPV
      treatment (p<0.05). Failure group had higher baseline heart rate than success
      group (p<0.05). CONCLUSION: Determination of baseline clinical factors such as
      heart rate and respiratory rate, available at the time of initiation and after a
      short period, can predict the likelihood of success or failure of NIPPV. As a
      result, delay in intubation can be avoided which itself is associated with
      significant mortality.

PMID- 16909732
TI  - A clinico-serological study of neurocysticercosis in patients with ring enhancing
      lesions in CT scan of brain.
AB  - AIMS OF THE STUDY: To study the clinical profile of neurocysticercosis and the
      utility of serological test using enzyme linked immunosorbent assay (ELISA) in
      patients with ring enhancing lesions in CT scan of brain. METHODS: A total of 51
      patients presenting between April 2003 to March 2004 to the Assam Medical College
      and Hospital, Dibrugarh, with ring enhancing lesions in CT scan of brain
      suggestive of neurocysticercosis were included in the study. Serum samples for
      ELISA test were taken from all patients and controlled sera were taken from 20
      patients admitted in the ward, who did not have clinical evidence of
      cysticercosis and whose CT scan of brain were either normal or revealed lesion
      other than cerebral cysticercosis. RESULTS: The maximum incidence of
      neurocysticercosis was found in the age group between 21 and 30 years (43.41%).
      Seizures were the commonest clinical presentation (100%). Eleven patients
      (21.56%) had ring enhancing lesions with central scolex. Fourty patients (78.44%)
      showed only ring enhancing lesions. ELISA test for definitive neurocysticercosis
      showed a sensitivity of 82.60% and specificity of 100%, while patients with CT
      scan features of neurocysticercosis had a sensitivity of 78.43% with ELISA.
      CONCLUSION: ELISA for cysticercosis showed a sensitivity of 82.60% and
      specificity of 100%. The study also shows that therapeutic effectiveness with
      albendazole is quite satisfactory. As the study population is small in number
      which was conducted in a span of one year, an evaluation with a larger number of
      patients will definitely throw more light on the subject.

PMID- 16909733
TI  - Prevalence of cardiovascular risk factors in Indian patients undergoing coronary
      artery bypass surgery.
AB  - BACKGROUND: Conventional cardiovascular risk factors (CVRFs) are known to
      influence short-term and long-term outcome following coronary artery bypass graft
      surgery (CABG). There has been recent increase in prevalence of CVRFs in general
      population in India. However no information is available regarding the prevalence
      of same in patients undergoing CABG. METHODS AND RESULTS: In this cross-sectional
      study, one thousand consecutive patients undergoing elective CABG were included
      and data on major CVRFs was obtained in them. Mean age of the patients was 59.73
      +/- 9.5 years and 884/1000 (88.4%) patients were males. 505/994 (50.8%) patients
      had BMI > or = 25.0 kg/m2 and 747/994 (75.2%) had BMI > or = 23.0 kg/m2. Diabetes
      mellitus was present in 475/1000 (47.5%) patients (46.5% men and 55.2% women),
      hypertension in 709/1000 (70.9% overall; 70.8% men and 71.6% women) and
      dyslipidemia in 781/913 patients (85.6% overall; 84.5% men and 93.9% women).
      213/913 (23.3%) patients had LDL > or = 100mg/dl, 662/913 (72.5%) patients had
      low HDL and 338/913 (37.0%) patients had elevated triglycerides. 199/1000 (19.9%)
      patients (18.7% men and 29.3% women) had family history of premature CAD and
      545/1000 (54.5%) patients (53.4% men and 62.9% women) had at least one family
      member having CAD (irrespective of the age of onset). 94/1000 (9.4%) patients
      (10.4% men and 1.7% women) were current smokers and another 302/1000 (30.2%
      overall; 33.7% men and 3.4% women) had history of smoking in the preceding one
      year. 876/913 (95.9%) of all the patients had at least one of the five major
      CVRFs and only 37/ 913 (4.1%) patients (4.1% men and 4.3% women) were free of all
      these risk factors. Sixty-one of the 1000 patients (6.1%) were younger than 45.0
      years of age. As compared to older patients, dyslipidemia, family history of
      premature CAD and smoking were commoner in patients less than 45 years of age. In
      contrast, diabetes and hypertension were more prevalent in the older individuals.
      CONCLUSIONS: The present study showed high prevalence of most of the conventional
      CVRFs, esp. diabetes, hypertension and dyslipidemia in Indian population
      undergoing CABG.

PMID- 16909734
TI  - Emerging role of vasopressin.
AB  - Ionotropic agents are frequently used in vasodilatory shock like conditions of
      septic or nonseptic origin. Conventional catecholamines such as norepinephrine
      are used at a very high dose with possibility of adverse effects in many
      patients. One often encounters refractoriness to these drugs. Infusion of
      vasopressin (VP) which is detectable at inappropriately low level in advanced
      phase of septic shock might allow withdrawal of catecholamines, as it maintains
      adequate mean arterial pressure (MAP), improves urine output and leaves perfusion
      of vital organs unhindered. Vasopressin has been found to be superior to
      epinephrine in animal models and some human trials, especially in patients with
      resistant ventricular fibrillation (VF) while doing cardiopulmonary resuscitation
      (CPR). Analogues of VP have also been used for diuresis in patients of
      hepatorenal syndrome.

PMID- 16909735
TI  - Marrow cryptococcosis in acquired immunodeficient patient.

PMID- 16909736
TI  - Osler-Weber-Rendu disease.

PMID- 16909737
TI  - Clinical approach to breast disorders: A primer for internists.
AB  - Women with breast disorders often present first to their internists for
      evaluation. A delay in accurate diagnosis could often result in worsening of
      prognosis for the patient. Common diagnostic problems include evaluation of a
      breast lump, nipple discharge and breast pain. Internist now has a choice of
      several diagnostic modalities to evaluate breast disorders. An evidence-based
      approach to common breast symptoms and advances in breast diagnostic techniques
      has been described to enable early diagnosis of breast cancer, thereby reducing
      the need for intensive treatments and improve patient satisfaction and clinical
      outcome.

PMID- 16909738
TI  - Adult type anomalous left coronary artery from pulmonary artery.
AB  - Anomalous origin of Left Coronary Artery from Pulmonary Artery (ALCAPA) is a rare
      congenital anomaly. Its survival into adulthood is further rare. Clinical
      manifestations result from evolving morphological - functional alterations in
      pulmonary circulation that occur after the birth. We report a case of 43 year old
      adult patient with effort angina and without any ECG or Echo abnormalities. On
      coronary angiography, typical anatomy of ALCAPA was revealed.

PMID- 16909739
TI  - A young female with quadriparesis.
AB  - We report a case of a young female who presented with acute onset quadriparesis
      secondary to severe hypokalemia. She was normotensive and had no metabolic
      alkalosis or kaliuresis. Serum potassium was corrected over the next few days and
      the quadriparesis resolved completely. A detailed history later on revealed that
      she had been consuming alternative medication for infertility for a prolonged
      duration and had discontinued it a month prior. One of the ingredients of this
      medicine was Glycyrrhiza glabra.

PMID- 16909740
TI  - Cerebral salt wasting syndrome in a patient with tuberculous meningitis.
AB  - We report a case of a 65 year male with meningitis who had polyuria, severe
      hyponatremia, volume depletion and very high urinary sodium excretion. He was
      diagnosed to have cerebral salt wasting syndrome based on clinical and laboratory
      parameters.

PMID- 16909741
TI  - Hyperleukocytosis associated pulmonary leukostasis in acute leukaemia.
AB  - Leukostasis is a fatal complication in granulocytic leukaemia. Brain and lung are
      most commonly involved organs in leukostasis. In the lung, the clinical
      presentation simulates infections and haemorrhagic complications of acute
      leukaemia. Being a medical emergency, early recognition of leukostasis and
      initiation of therapy prevents mortality.

PMID- 16909742
TI  - Medical philately (medical theme on stamps). Alfred Nobel (1833-1896).

PMID- 16909743
TI  - Hypomagnesaemia masquerading as hypoparathyroidism.
AB  - Magnesium deficiency is a common clinical problem. Dietary malabsorption and
      renal wasting are the commonest causes. Hypomagnesemia induces a state of
      functional hypoparathyroidism due to decreased secretion of parathormone (PTH) as
      well as resistance to its action. Contrary to typical autoimmune
      hypoparathyroidism, it is associated with decreased levels of serum phosphate. We
      report a patient who presented with hypocalcemic tetany associated with
      hypomagnesaemia due to renal wasting. Subsequently, he improved with magnesium
      supplementation of therapy.

PMID- 16909744
TI  - Severe hypoglycemia due to poorly differentiated hepatocellular carcinoma.
AB  - Hypoglycemia is a well documented paraneoplastic syndrome of hepatoma.
      Hypoglycemia as sole presentation is very rare. We report a case of poorly
      differentiated hepatoma with multiple lung metastases presenting with recurrent
      hypoglycemic seizures as the only manifestation four months before the diagnosis
      of the tumour.

PMID- 16909745
TI  - Acute proptosis as an initial presentation of bronchogenic carcinoma.

PMID- 16909746
TI  - Hepatitis E infection with Bell's palsy.

PMID- 16909747
TI  - Speaking the same language: Georgia providers cross language barriers.

PMID- 16909748
TI  - A call to action on certificate of need (CON).

PMID- 16909749
TI  - Inspector General discusses self-disclosure initiative in open letter.

PMID- 16909750
TI  - Former PHA Chair takes patient safety message to national level.

PMID- 16909751
TI  - [Melatonin recovers ischemic tolerance and decreases the sensitivity of
      mitochondrial permeability transition pore opening in the heart of aging rats].
AB  - The effect of the hormone of pineal gland melatonin on the ischemic tolerance and
      the sensitivity of mitochondrial permeability transition pore opening in old rat
      heart were studied. It has been shown in the Langendorf's isolated rat heart that
      heart contractile functional changes under ischemia and reperfusion were more
      pronounced in old (24-27 months) rat hearts in comparison with the adult (5-6
      months) animals. A two-week's in vivo course of intraperitoneal injection of
      melatonin (1,5 mg/kg weight) to old rats contributed to the rehabilitation of the
      functional changes of isolated heart after ischemia during reperfusion and
      decreased the sensitivity of mitochondrial permeability transition pore opening
      to Ca2+ and phenilarsinoxide in comparison with old animals which did not
      received melatonin. It was accompanied by the significant decreasing in mRNA bax
      expression in old rat heart, lessening in content of the superoxide radicals and
      dien conjugates and twice increasing in the activity of constitutive NO-synthase
      in heart mitochondria of old rat after a course of melatonin injection. The
      protective feffect of melatonin on the mitochondrial permeability transition pore
      opening could be used for correction of the cardiac dysfunction with aging.

PMID- 16909752
TI  - Proteasome inhibitors eliminate protective effect of postconditioning in cultured
      neonatal cardiomyocytes.
AB  - A role of proteasomal proteolysis in the pathogenesis of ischemia-reperfusion is
      being actively studied. To evaluate the participation of the proteasome in
      postconditioning phenomenon, we used primary culture of neonatal cardiomyocytes.
      30 minutes of anoxia followed by 60 minutes of reoxygenation was undergone.
      Postconditioning was modeled by 3 cycles of 1-minute reoxygenation followed by 1
      minute anoxia, respectively. Clasto-lactacystin b-lactone, a specific proteasome
      inhibitor, in the dose that does not cause cell death (2.5 mM) was added to the
      culture medium just before the cycles of postconditioning. 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 led to an increase in trypsin-like and chymotrypsin-like activities
      comparing to anoxia, but these parameters never reached the control levels. PGPH
      activity was restored up to the initial level. 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 postconditioning. The data
      obtained permit to suppose that proteasome inhibitors can be used for
      pharmacological postconditioning.

PMID- 16909754
TI  - [The role of Na+,K+ ATPase in electrogenicity of the aortic endothelial cells].
AB  - The role of Na pump in the regulation of the membrane potential of endothelial
      cells of rat isolated aorta at rest and during stimulation by acetylcholine was
      investigated. Inhibition of Na pump by 500 mcM ouabain and potassium-free
      solution depolarized endothelial cells by 11 mV. Na pump reactivation caused by
      potassium restoration hyperpolarized endothelium by 18 mV, this hyperpolarization
      was sensitive to 500 mcM ouabain. Potassium-free solution and ouabain attenuated
      the duration of the acetylcholine-evoked hyperpolarization. The results presented
      demonstrate that the sustained hyperpolarization of endothelial cells to
      acetylcholine in rat aorta may be partially mediated by Na pump stimulation.

PMID- 16909753
TI  - [The influence of the fluorine-containing activators of mitochondrial adenosine
      triphosphate sensitive potassium channels on the oxidative phosphorilation].
AB  - The cardioprotective mechanism of KATP channel openers and especially their
      influence on mitochondrial respiration has not been clarified yet. In this
      article we investigated the effect of DiazoFm and DiazoFp, the new fluor
      containing analogues of diazoxide and the potential mitochondrial KATP channel
      openers, on the oxidative phosphorylation in the isolated mitochondria. It was
      shown that the influence of KATP channel openers on ADP-stimulated oxygen
      consumption (State 3) depended on the substrates we used (succinate or 2
      oxoglutarate sodium). We have shown that the depression of State 3 was less when
      we used DiazoFm (30 MM) and DiazoFp (30 MM) in comparison with Diazoxide in
      experiments where succinate was used. The fluor-containing KATP, channels openers
      did not significantly change the activity of succinate dehydrogenase in
      comparison with diazoxide (it decreased succinate dehydrogenase activity by 27%).
      Thus, the fluor-containing analogues of diazoxide did not significant influence
      on the complex II of the respiratory chain. In the other experiments when we used
      2-oxoglutarate sodium as an oxidative substrate, DiazoFp increased ADP-stimulated
      oxygen consumption by 33%. All the studied KATP openers have an uncoupling
      effect, regardless the substrates we used. This effect was more significant when
      we used succinate as a substrate. We have shown that the uncoupling effect of
      oxidative phosphorylation is a consequence of K channels activation. This
      statement was proved by 5-hydroxydecanoate (200 MM) with depressed influence of
      Diazoxide and its fluoring-containing analogues. Conclusion. The fluor-containig
      KATP channels openers had not direct influence on the respiratory chain in
      mitochondria, but activation mitochondrial KATP channels by them lead to
      uncoupling phosporylation and respiration.

PMID- 16909755
TI  - [The role of short chain fatty acids and lactate in regulation of the gastric
      secretion].
AB  - The investigation was carried out in acute experiments by means of isolated
      stomach perfusion by Ghosh and Shild and in chronic experiments in dogs with
      fistula of the stomach and duodenum. In rats with intact nervous system lactulose
      as the source of short chain fatty acids (SCFAs) diminished basal and stimulated
      by insulin, pentagastrin and histamine gastric acid secretion. By contrast it did
      not influence carbachol gastric acid secretion. In dogs with intact nervous
      system lactulose also suppressed the intensity, debit of acid and pepsin of
      gastric juice stimulated by insulin and histamine. It suggests that the effect of
      lactulose does not dependent on kinds of animals. Truncal vagotomy removed the
      inhibitory action of lactulose on pentagastrin and histamine gastric acid
      secretion in rats. SCFAs and lactic acid suppressed pentagastrin gastric acid
      secretion in rats. Lactulose, propionate potassium, lactate potassium enhanced
      the blood glucose level. Truncal vagotomy did not influence the increase of the
      blood glucose level evoked by lactulose. It is concluded that SCFAs decreases
      gastric secretion in the third intestinal phase through central inhibition. The
      mechanism of inhibitory action of lactic and propionic acids depends on their
      role in the liver gluconeogenesis which leads to increase of the blood glucose
      level. Hyperglycemia as it is known suppress gastric secretion through
      diminishing of neural cholinergic activity of nerves vagus.

PMID- 16909756
TI  - [Death of the ovarian follicular cells in mice with impaired oogenesis of the
      immune nature].
AB  - An impairment of the meiotic maturation of the oocytes has been shown in vitro
      for 2 types of immune damage of the ovaries in mice induced by xenogenic
      antiovarial antibodies and immunization with allogenic ovaria. Impairment of the
      oogenesis was followed by the follicular cell death, primarily by on the apoptic
      way, but under the immunization with allogenic ovary a necrotic way of their
      death was also activated.

PMID- 16909757
TI  - [Changes in activity of the hypothalamic neurons in response to physiological
      fluctuations of the homeostasis constants].
AB  - In acute experiments on cats under the combined narcosis (ketamine + N2O) we have
      investigated impulse activity of the rostral hypothalamic neurons and analyzed
      its modifications due to visceral stimulation. As stimulation we used warmed up
      or cooled (on 7 degrees C) a paw of an animals, cooled a body of an animal, we
      administered solutions into a carotid artery: 5 % of glucose, 0,2 % and 3 % NaCl,
      phenilephrine. Thus we modeled fluctuation of homeostasis's constants in
      physiological limits in an animal organism. It is shown that the greatest
      quantity of investigated neurons--more than 10 % authentically changes a pattern
      impulse activity when we entered solutions of 5 % of glucose and 0,2 % NaCl into
      a carotid artery of animals. In other cases the degree of transformation of a
      pattern was less (6-7 %) and approximately identical. When we entered of a
      microdose phenilephrine into the v. femoralis in order to modulate press effect
      we registered minimal quantity of neurons (1,4%). Studing of the parameters of
      the IA hypothalamic neurons during the homeostatic changes could be a basis for
      finding of transformation of the functional state of neurons which take part in
      the regulator mechanisms for maintaining of homeostasis.

PMID- 16909758
TI  - [Effect of allogenic intracranial transplantation of embryonal neural cell
      precursors on the humoral immune response to neurospecific proteins in rabbits].
AB  - The purpose of the study was to prepare the neural precursors and evaluate the
      humoral autoimmune response to neuro-specific antigens in rabbits after
      intracranial transplantation of the prepared cells. The cell suspension enriched
      with vimentin-positive progenitor neurocells up to 70-80% was received on 9th day
      after cultivation of embryonal rabbit neurocells in DMEM+retinol acetate medium.
      The autoimmune responses to neuronspecific enolase were established in 30% of
      rabbits 1-3 months after intracranial neural precursors transplantation.

PMID- 16909759
TI  - [Inhibitory reactions of the motor cortex neurons in the triggering of
      conditioned reflex organization in cats].
AB  - The neuronal impulse reactions of the motor cortex neurons (field 4) which are
      involved in the reflex realization were studied on the awakening cats trained to
      perform conditioned movement after the influence of two stimuli (the preliminary
      and the conditional). Slow cortex potential in vertex was registered
      simultaneously. It was established that before the response to the triggering
      signal (interstimuli period) high amplitude negative shift in the slow cortex
      potential is present. At the same time we registered inhibition of neuron
      activity which led to excitative reactions represented as potent impulses. The
      obtained results allow us to suggest a relationship between the development of
      negativeness and inhibition of motor cortex neurons during preparation to the
      movement.

PMID- 16909760
TI  - [Effect of the genetic factor and nociceptive stimule on the development of
      visceral pain].
AB  - The experimental research of painful behavioural reaction on nociceptive visceral
      stimulus with outinbred white and of the C57BL/6J and CBA/ CaLac genetic strains
      of mice was carried out. Influence of intraperitoneal administration of the
      different volumes and concentration of acetic acid solution on visceral painful
      behavioural reaction at these animals was shown. It was found that CBA/ CaLac had
      a higher intensity of visceral painful behavioural reaction (on 32 %), than
      C57BL/6J strain. Comparison of intensity of behavioural reactions to a somatic
      pain in these animals (the formalin test) has shown that at CBA/CaLac this
      intensity was lower by 48.5 % than in C57BL/6J strain. Such distinctions in the
      character of behavioural reactions on somatic and visceral pain may be caused by
      features of the functional organization of the brain central structures
      participating in the formation of visceral and somatic reflexes at these two
      genetic strains.

PMID- 16909761
TI  - [Age-dependent characteristics of blood plasma oxidative and antioxidative
      reactions to the hypobaric hypoxia and different duration of the photoperiod].
AB  - The effect of hypobaric hypoxia (6 hours everyday 7 days) under different
      duration of the photoperiod on oxidative (malonic aldehide and dienal conjugates)
      and antioxidative (catalase and superoxide dismutase activity) systems in the
      blood plasma of adult and infantile albino male rats were investigated. It is
      concluded that there is an age-dependent reaction of oxidative and antioxidative
      systems to the combined action of hypobaric hypoxia and different duration of the
      photoperiod. Reactions of pro- and antioxidative systems of adult and infantile
      rats were approximately the same under the conditions of a long-term darkness-and
      hypoxia but in the infants they were less manifested under the combined action of
      hypoxia and natural light or long-term lightening. Hypoxia combined with all
      varieties of photoperiod activate antioxidative system in both age groups but
      only in infantile rats the process of peroxidation was reducing.

PMID- 16909762
TI  - [Effect of amaranth oil and intermittent hypoxic training on ultrastructural and
      metabolic changes in the liver induced by fluorine and low doses of radiation].
AB  - Ultrastructural and metabolic changes were studied during chronic fluorine
      intoxication and low doses of radiation (total dose is 1 Gr) in liver cells and
      tissues in rats fed with amaranth oil and treated with intermittent hypoxic
      training (IHT). The obtained data detected the ordered and compact position of
      mitochondria, peroxisomes, lipoprotein droplets with light electronic density,
      glycogen granules and also agranular endoplasmatic retuculum channels, which may
      be linked with reorganization of metabolic pathway of energy supply from fat
      acids via gluconeogenesis. Simultaneously the decrease of TBA-reactive substances
      accumulation with the considerable increase in activity of the antioxidant
      enzymes (catalase, glutathione peroxidase) and index of general antioxidant
      activity have been established. Therefore, the combined effect of IHT and
      amaranth oil on adequate occurence of free radical reactions provides the
      effective adaptation of organism to fluorine intoxication and ionizing radiation
      via the restoration of homeostasis on metabolic and ultrastructural levels. The
      obtained results allow to recommend IHT and amaranth oil for complex correction
      of changes, induced by fluorine intoxication and ionizing radiation.

PMID- 16909763
TI  - [Effect of the vascular wall tissue on platelet functional activity in rats
      during water and salt loading].
AB  - It was shown in vitro that platelets of rats which were exposed to high-salt diet
      (3 % NaCl solution) possess the least functional activity, especially after
      addition of the vascular wall tissue to the incubating medium compared to intact
      rats, which had water load.

PMID- 16909764
TI  - [Retrograde signaling in the GABA- and glutamatergic synapses of the brain].
AB  - According to classical concept, due to chemical synapses, information in the
      central nervous system is transferred in one direction: from presynaptic neurons
      to postsynaptic ones. Although several cases of information transfer in the
      opposite direction were known for a long time, those were considered as rare
      exceptions. However, recent results indicate that retrograde signaling between
      brain neurons is rather a common phenomenon. In this review we will focus on two
      related forms of short-term plasticity of GABAergic and glutamatergic synaptic
      transmission observed in several brain structures and mediated by retrograde
      messengers endocannabinoids. Namely, we will characterize phenomenon termed
      "depolarization-induced suppression of inhibition", observed at GABAergic
      synapses and related phenomenon observed at glutamatergic synapses named
      "depolarization-induced suppression of excitation".

PMID- 16909766
TI  - The first in the family to be supersized.

PMID- 16909765
TI  - Transmission of male infertility and intracytoplasmic sperm injection (mini
      review).
AB  - The fact that genetic aetiology is responsible for approximately one third of all
      kinds of male sterility has led to concerns regarding the application of
      artificial reproductive technologies in the cases of azoospermia and severe
      oligozoospermia. Congenital sterility could be caused by gene mutation,
      quantitative or structural abnormality of sexual chromosomes or autosomes. The
      possibility of inherited transmission of male sterility within the context of
      applying artificial reproductive technologies is analysed in the article.
      Klinefelter's syndrome, mutation of cystic fibrosis transmembrane conductance
      regulator (CFTR) gene, which causes cystic fibrosis, and mutation of azoospermia
      factor zone (AZF) of Y-chromosome are among the most frequent genetic causes of
      severe oligozoospermia and azoospermia. The probability of a mutation of the CFTR
      gene being transmitted to the next generation is 50%. The probability of inherit
      transmission of Klinefelter's syndrome of mosaic karyotype could reach 70%. The
      probability of transmission of AZF mutation to children of male sex, generated
      with ICSI, is 100%. The percent of men with AZF mutation among users of ICSI
      centers, ranges from 3.2% to 14%. It means that at least 3.2 % of all boys
      conceived with ICSI will be sterile because of mutation in the AZF zone of Y
      chromosome. It should be noted that genetic analysis and counselling do not
      always occur before the beginning of artificial fertilization cycles. Parents-to
      be do not always have an opportunity to learn about the genetic risks of their
      unborn child and make any subsequent and responsible decisions. Among the
      decisions is a choice of not resorting to ART, but to live with the infertility
      and explore other opportunities for parenthood. Responsibility for high risk of
      conceiving a child with genetic anomalies rests not only with the parents, but
      also with all of society, including those responsible for research, technology,
      and legislation, in the health care profession.

PMID- 16909767
TI  - A very private moment.

PMID- 16909768
TI  - One 'reform' that worked.

PMID- 16909769
TI  - [Tick-borne diseases exposure of forestry workers and preventive methods usage].
AB  - Forestry workers are a group of a high risk of occupational exposure to tick
      borne diseases. The group of 51 healthy persons with a history of more than 3
      years forestry working was tested for antibodies against B. burgdorferi and tick
      borne encephalitis (TBE) and reviewed on tick-bites preventive methods usage. Two
      steps serological examination revealed the anti-B. burgdorferi antibodies in 14
      (27.5%) persons. Anti-TBE antibodies were present in 6 (11.8%) persons. Despite
      of multiple tick bites in anamnesis, methods of ticks bites prevention (clothes,
      repellents) were used by less than 30% of workers. Similarly, anti-TBE
      vaccination was conducted only in 11 persons. Concluding, the elaboration of
      educational, prophylactic and efficacy monitoring standards for this occupational
      group is needed.

PMID- 16909770
TI  - [Specific features of Borrelia burgdorferi infection in children].
AB  - Clinical picture of Borrelia burgdorferi infection has been presented in 89
      children from Lodz region. The analysis showed significant domination of cases
      with non specific symptoms (41.6%) as: fever or headache and cases with affected
      central and peripheral nervous system (30.3%). Peripheral cranial nerves
      paralysis and symptoms of cerebrospinal meningitis dominated among children with
      neuroborreliosis. Unlike descriptions concerning adults, majority of the observed
      symptoms were changes characteristic for I stage of the disease. Dermatosis was
      found only in (19%) child and symptoms of arthritis in (9%) of them. Contact with
      tick was stated in 56.8% of the analysed children. Incidence of the disease
      occurred throughout the whole year, more frequently in summer and autumn months.

PMID- 16909771
TI  - [Influenza--old medical problem].
AB  - Influenza surveillance and increase of the percentage of population vaccinated
      against influenza have priority significance to combat influenza. In Poland 8.3%
      of the population have been vaccinated against influenza during the last epidemic
      season. Consequences of influenza infections are medical as well as economic. In
      the USA economic costs of influenza range, depending on the epidemic season, from
      76 billions to 167 billions US dollars. WHO, prestigious Scientific Societies and
      European Union appeal to increase influenza vaccination coverage. These
      vaccinations are the most effective and the cheapest way to fight against
      influenza. During 6 years avian influenza virus, breaking species barrier, caused
      death of over 100 persons. Despite culling of millions of poultry, influenza
      virus A/H5N1/ caused infections in birds in many countries. There is unanimous
      conviction that the next influenza pandemic is an inevitable event. At present,
      it is not possible to answer two questions: when it will happen and what subtype
      will cause pandemic. All countries were obliged to prepare emergency plans for
      the next influenza pandemic.

PMID- 16909772
TI  - [Tick-host interactions].
AB  - Ticks are dangerous blood-sucking ectoparasites of medical and veterinary
      importance. They serve as reservoirs and vectors pathogens and cause direct skin
      damage by feeding. Tick saliva contains pharmacologically active molecules
      directed against host's immune system and effector pathways. Ticks feeding induce
      hosts' inflammatory and immunological reactions of host comprise both innate and
      acquired immunity.

PMID- 16909773
TI  - [Ultrasonography in diagnosing Lyme arthritis of the knee joints in correlation
      with anti-CCP antibodies].
AB  - Lyme disease, a multi-system disorder may be associated with arthritis. Lyme
      arthritis most commonly affects the knee joints. Ultrasonography can show the
      inflammation changes of the knee joint and can be a usefull method in diagnosis
      of Lyme arthritis. The most freguent ultrasonographic finding was knee joint
      effusion. Because of Lyme arthritis similarities to rheumatoid arthritis, a
      serologic test antibodies against cyclic cytrulinated peptid (anty CCP) can be
      helpfull in distinguishing of these two diseases.

PMID- 16909774
TI  - [Multifocal central nervous system lesions --multiple sclerosis or
      neuroborreliosis?].
AB  - Multiple sclerosis is the most frequent multifocal disease of the central nervous
      system, but in a diagnosis of atypical cases about 100 other diseases should be
      considered. Neuroborreliosis plays a particular role among them, especially in
      endemic regions. Difficulties result from similarities of clinical symptoms and
      lack of specific diagnostic investigations. Diagnostic procedures in
      neuroborreliosis are mostly based on laboratory analyses and serologic
      examinations of serum and cerebrospinal fluid, in connection with a clinical
      picture and an epidemiological state. Since the year 2001, multiple sclerosis
      neurological diagnostic is based on the diagnostic criteria established under the
      auspices of The US National Multiple Sclerosis Society and International
      Federation of Multiple Sclerosis Societies. Those recommendations regarding
      relapsing-remitting MS and primary progressing MS are discussed in this paper.
      Current knowledge of those diseases warrants cautiousness in the diagnostic of
      atypical cases.

PMID- 16909775
TI  - [Serious course of sepsis in diabetic patients].
AB  - The aim of the study was to evaluate the frequency and the course of sepsis in
      the patients treated in our ward. Retrospective evaluation was conducted on a
      group of 7418 patients hospitalized in 2001-2005. Serious sepsis was found in 15
      patients (0.2%). Analysis was conducted on two groups of patients: diabetic
      (group A) and non-diabetic (group B). The majority of patients had community
      acquired infection (93.3%). Critical course of sepsis was observed in 53.3% of
      patients. Mortality was higher in group A (83.3%) compared to B (33.3%). In group
      A other, pre-existing diseases were more frequent. The most frequent focus of
      infection was urinary tract, followed by respiratory system. In group A the focus
      of infection was in 33.3% each urinary tract, respiratory tract and diabetic
      foot. Only in 66.7% of patients pathogens were cultured from body fluid. Multiple
      pathogens were more frequent in group B. Co-existing fungal infections were more
      frequent in group A (16.6%) than in B (11.1%). The empirical therapy was
      ineffective in 75% of diabetic and 50% of non-diabetic patients. CONCLUSIONS: 1)
      In severe sepsis mortality is high, and in diabetic patients it amounts to 80%.
      2) In > 30% patients bacteriological tests did not confirm the type of pathogen.
      3) In diabetic patients fungal infections were more frequent. 4) Critical course
      of sepsis may result from co-existing morbidity.

PMID- 16909776
TI  - [The value of prophylactic serological tests for syphilis in the region of
      Bialystok in years 1994-2004 (before and after the introducing the health care
      system reform in Poland)].
AB  - The prophylactic serological tests for syphilis (psts), belong to the principal
      methods of controling the spread of the disease. The aim of the study was to to
      analyze the epidemiological efficacy of psts performed in Bialystok region before
      and after the health care system reform. The results of psts performed in 1994
      1998 (N = 752.787) and in 1999-2004 (N = 407.366) were analyzed. The average
      annual number of psts declined from 150.557 to 68.687 in two periods analyzed,
      respectively. The lowest number of tests performed (51.654) was noticed in 2004.
      Sixty-one of 117 (52.14%) and 30 of 52 (57.97%) syphilis cases have been detected
      owing to psts in two periods analyzed, respectively. The efficacy index of psts
      was highest in convicts or prisoners and in pregnant women in both periods (172,1
      and 134,6 and 67,9 and 50,7, respectively). The significant decline in efficacy
      index was noticed for tests performed as periodic prophylactic examinations of
      employees and prior to employment. The results indicate that psts remain one of
      the most efficient methods of diagnosis and prevention of syphilis despite the
      decline in the number of the tests and the formal renouncement of the screening
      among convicts and prisoners since 2003. Low syphilis incidence rate in Poland
      can be, in part, own to diminished number of performed tests. There is a need for
      the parallel studies in other regions of Poland.

PMID- 16909777
TI  - [Different diagnosis:Lyme arthritis or rheumatoid arthritis].

PMID- 16909778
TI  - [Preliminary studies on presence of antineuronal antibodies in serum of patients
      with Lyme borreliosis].
AB  - Wide spectrum of autoantibodies reactive against neuronal antigens was detected
      in sera of 32 of 50 studied patients with Lyme borreliosis. This may be
      potentially of importance in the pathogenesis of neuroborreliosis.

PMID- 16909779
TI  - [Biochemistry of hepatic encephalopathy].
AB  - Authors discuss pathogenesis and biochemistry of hepatic encephalopathy in the
      course of acute hepatic failure and hepatic cirrhosis.

PMID- 16909780
TI  - [Creutzfeldt-Jakob disease--the past or the future].
AB  - Some recent views on ethiopathogenesis and epidemiology of four main forms of
      CJD, based on up to-day experiences and expectations for the future, are
      presented. The sporadic form of the disease (sCJD) displays a stable morbidity-
      ca. 1 case/1 million population yearly. The reasons of its so constant appearance
      remain still unknown. The familial forms of CJD (fCJD) depending upon more than
      40 mutations in PRNP gene known today are inherited as autosomal dominant train.
      The clinical and neuropathological phenotype of patients belonging to various
      families are usually very different. The best epidemiological prognosis is
      attributed to iatrogenic form of CJD (iCJD), since both the medical errors
      causative of the disease and methods of avoiding of them are now very good
      recognized. The serious fears in many countries raises variant CJD (vCJD),
      connected etiologically with BSE, because of unknown duration of its incubation
      period and regular chronic involvement by prions reticulo-lymphatic tissue in
      infected persons.

PMID- 16909781
TI  - [Helicobacter pylori infection in children and socio-economic factors].
AB  - The aim of the study was to find a correlation between the presence of
      Helicobacter pylori infection in children and their accommodation and socio
      economic conditions. The results of questionnaire studies were analyzed and
      levels of IgG specific antibodies against H. pylori were assessed in children
      randomly chosen in the north-east of Poland at the level of a district, county
      and province city. The incidence of H. pylori infection in the studied children
      was varied and depended on the living place. The highest percentage of the
      infected was revealed in a district (40.4%) and the lowest in a province city
      (19.0%). There was a correlation between H. pylori infection and socio-economic
      conditions. The highest percentage of the infected children (59.7%) was found in
      families whose income was within the first income tax group. The incidence of the
      infection was also determined by the type of a flat, the number of members in a
      family, water intake and personal hygiene. CONCLUSIONS: 1) the highest incidence
      of H. pylori infection in children was found in a county, the lowest in a
      province city. 2) environmental and socio-economic conditions influence the
      presence of H. pylori infection in children.

PMID- 16909782
TI  - [Familial transmission of Helicobacter pylori infection in Podlasie Region].
AB  - The purpose of the study was to assess the incidence of Helicobacter pylori
      infection in members of families in the Podlasie Region. The study included
      members of 205 families in whom IgG antibodies against H. pylori were determined.
      The mean number of members examined in a family was 3.07. The mean age was 16.6
      years; the mean level of specific IgG antibodies was 67.35 U/ml. Of the families
      examined 47 (22.0%) had all members with a positive titer of antibodies against
      H. pylori (> 24 U/ml); in 62 (30.2%) families, all members presented a negative
      result of IgG antibodies against H. pylori (< 24 U/ml). Of 97 mothers examined, a
      positive titer of IgG was found in 77.1%. Of 33 fathers (81.8%) were
      seropositive. In the families with a mother seropositive, the infection in at
      least one child examined was revealed in 48.6% of the families, whereas in the
      families with a mother seronegative, all her children were healthy in 63.6% of
      the families. In case of a father, a positive IgG in at least one child was found
      in 55.5% of the families, whereas no infection in children was estabilished in
      44.4%.

PMID- 16909783
TI  - [Vaccination against poliomyelitis].

PMID- 16909784
TI  - [Burden of hospitalization of children with viral meningitis in Bialystok, 2003
      2005].
AB  - OBJECTIVE: This study examined the burden of hospitalization of children with
      viral meningitis in Department of Pediatric Infectious Diseases, Medical
      University of Bialystok from 2003 to 2005. METHODS: Data were extracted from
      Children Teaching Hospital database. A hospitalization with viral meningitis was
      defined as any discharge with diagnoses of mumps meningitis (B26.1), enteroviral
      meningitis (A85.0), tick-born encephalitis (A84.1) and viral undifferentiated
      meningitis (A87.9) due to ICD-10. Outcome measures included number of
      hospitalizations in total and due to different etiology as well as their impact
      in the budget of the unit. RESULTS: 316 hospitalizations with viral meningitis
      were identified. Of these 246 (77.6%) were diagnosed with mumps etiology, 10
      (3.2%) with enteroviral, 1 (0.3%) with tick-born virus and 59 (18.7%) with
      unknown viral etiology. Most cases of viral meningitis were hospitalized in 2003-
      132 (41.8%). Of these 93.9% were diagnosed with mumps meningitis. In 2005, of 78
      hospitalizations associated with viral meningitis 10 (12.8%) were confirmed and
      further 38 (48.7%) were suspected enteroviral meningitis. The percentages of
      costs associated with viral meningitis in 2004 and 2005 (26% and 18.8%) were high
      in comparison to percentage of hospitalizations with viral meningitis (10.7% and
      7.3%, respectively).

PMID- 16909785
TI  - [Complications of tick-borne encephalitis in 15-year long experience of the
      Department of Infectious Diseases and Neuroinfections].
AB  - The clinical features of tick-borne encephalitis (tbe) were analyzed in the group
      of 477 patients hospitalized in the Department of the Infectious Disease and
      Neuroinfections of the Medical Academy in Bialystok. The group included 31.4%
      women and 68.6% men, aged from 15 to 76 years. Persistent neurological sequelae
      were noted in 10.9% of patients: paresis or plegia in 5.66%, spinal dysfunction
      with lower limbs paraparesis in 1.68%, significant paresis of upper extremities
      in 0.63%, brachial plexus paresis in 2.31%. Cranial nerves involvement was
      present in 2.93%, including uni- or bilateral facial nerve palsy in 2.73% and
      trigeminal nerve involvement in 0.21%. Cerebellar dysfunction was present in
      2,09% of patients. No fatal cases of tbe occured.

PMID- 16909786
TI  - [Assessment of antioxidative defense parameters in serum and age of patients
      showing antibodies anti-Borrelia burgdorferi presence--non-symptomatic carriers].
AB  - To evaluate in serum antioxidative deffence parameters--SOD EC.1.15.1.1
      (superoxide dismutase), GSH-Px EC.1.15.1.1 (glutathine peroxidase), -SH
      (sulphhydryl groups) among patients previously diagnosed with borreliosis
      presently showing antibodies against Borrelia burgdorferi presence. The
      antioxidative deffence parameters were evaluated in 117 sera of patients with
      previously diagnosed borreliosis aged x = 43,07. Control group consisted of 39
      persons aged x = 40,97 with no detectable anti-Borrelia burgdorferi antibodies in
      serum. Serologic diagnosis was performed with use of ELISA kit--Borrelia
      rekombinat IgM, IgG (Biomedica, Austria). Serum activity of antioxidative
      deffence parameters-- SOD EC.1.15.1.1 (superoxide dismutase), GSH-Px EC.1.15.1.1
      (glutathine peroxidase), -SH (sulphhydryl groups) were detected in all patients
      from both groups. Obtained results were statistically analysed. There was showed
      no significant difference in serum activity of SOD and GSH-Px in group of former
      borreliosis patients and control group. Also serum -SH concentration did not
      differ significantly between both examined groups of patients. No correlation
      between SOD and GSH-Px serum activity as well as -SH concentration was detected.

PMID- 16909787
TI  - [Intercellular adhesion molecules sICAM-1, sICAM-2, sICAM-3 and IFNgamma in
      neuroborreliosis and tick-borne encephalitis].
AB  - OBJECTIVE: The aim of this study was to evaluate the serum and CSF concentration
      of soluble intercellular adhesion molecules sICAM-1, sICAM-2, sICAM-3 and
      proinflammatory cytokine IFNgamma in patients with tick-borne encephalitis (TBE)
      and neuroborreliosis. METHODS: The study group consisted of 40: 20 with TBE
      meningitis and 20 with Lyme meningitis. The serum and CSF levels of adhesion
      molecules and IFNgamma were determined by ELISA assay twice: before and after
      treatment. RESULTS: Before treatment the concentrations of adhesion molecules and
      IFNgamma in serum as well as in CSF were significantly higher in both studied
      groups than in control group (with the exception of the serum level of sICAM-2 in
      TBE group). After the treatment, the serum parameters in TBE group decreased to
      the control level. CSF levels were also reduced, but still remained higher than
      in the control group. In patients with neuroborreliosis serum concentration of
      sICAM-1 and sICAM-2 did not change as compared with its level before treatment
      but other studied parameters in serum and CSF decreased significantly.
      CONCLUSIONS: The results of our study confirm the participation of intercellular
      adhesion molecules in the pathogenesis of viral (TBE) and bacterial
      (neuroborreliosis) neuroinfections.

PMID- 16909788
TI  - [Rotaviruses and adenoviruses as etiologic factors of diarrhoeas at children].
AB  - Viral diarrheas are important clinical and epidemiological problem, especially in
      small children. In the years 2004-2005 in the Pediatric Ward of the SPZOZ in
      Hajnowka, among 218 children aged from 0 to 7 years hospitalized with symptoms of
      the acute diarrhea, rotavirus infection was confirmed in 35.8% and adenovirus in
      5.1%. Hospital infections were observed in 0.96% of children hospitalized in the
      Pediatric Ward for reasons other than the acute diarrhea. The morbidity presented
      with seasonality characteristic for the temperate climate.

PMID- 16909789
TI  - [Diagnosis and treatment of Lyme arthritis].
AB  - Lyme disease is a multisystem disease that affects primarily skin, nervous
      system, heart and joins. Lyme disease is caused by Borrelia burgdorferi and
      spread by Ixodes ticks. Arthritis is a well-known manifestation of Lyme disease
      (LD). Joint symptoms associated with B. burgdorferi infection range from
      arthralgias, to brief attacks of arthritis, to chronic erosive synovitis.
      Arthritis may present as oligo- or monoarthritis and typically causes
      intermittent attacks of oligoarticular arthritis in a few large joints,
      especially the knee. A small percentage of patients may develop chronic
      arthritis. The diagnosis is usually based on the clinical picture, exposure in an
      endemic area, and detection of IgG antibody against B. burgdorferi by ELISA and
      Western blotting. Spirochetal DNA may be detected in joint fluid by PCR.
      Antibiotic treatment during early stages normally prevents development of late
      manifestations. Joint involvement is treated successfully with a 1-month course
      of doxycycline or ceftriaxone. However, about 10% of Lyme arthritis patients do
      not respond sufficiently to antibiotic treatment. If patients have persistent
      arthritis despite a second course of antibiotics with negative results of PCR
      testing, treatment with anti-inflammatory agents or arthroscopic synovectomy is
      possible. In this article, we discuss clinical features, diagnosis and treatment.

PMID- 16909790
TI  - [Active monitoring of hospital infections in public hospital in Staszow].
AB  - The study aim was to evaluate effectiveness of epidemiological surveillance in
      Public Health Care Center in Staszow. Active surveillance significantly increased
      the detection rate of hospital infections. It was determined that active
      surveillance should be aimed at patients hospitalized in intensive therapy wards,
      undergoing surgery, older than 70 years and neonates. Short-time active
      monitoring of other selected groups of patients (e.g. with intravenous catheter,
      vesical catheter, with decubitus ulcer) is also advisable.

PMID- 16909791
TI  - [Etiologic factors of acute gastroenteritis in the patients from infectious and
      pediatric wards in SP ZOZ in Hajnowka in 2004-2005].
AB  - Acute infections of the digestive tract, clinically presenting as acute
      gastroenteritis, may have different ethiologic basis. Both bacteria (Escherichia
      coli, Enterobacter spp., Salmonella spp.) and viruses (Rotaviruses, Adenoviruses)
      are frequently isolated ethiologic factors. In some cases the ethiologic factor
      cannot be detected.

PMID- 16909792
TI  - [Mixed aphasia as a dominating symptom of encephalitis].
AB  - Encephalitis has typically a severe course, with psychotic disorders,
      consciousness disorders, epileptic seizures and meningal signs. The author
      describes a case of a young male, in whom dominant symptoms of encephalities were
      aphasia and headache. These symptoms were accompanied by considerable
      inflammatory changes in cerebral fluid. The outcome of illness was favourable.

PMID- 16909793
TI  - [The acute cerebellar ataxia, reccurrence of disease after 5 years--a case
      report].
AB  - Acute cerebellitis, also known as acute cerebellar ataxia, is a rare inflammatory
      syndrome characterized by cerebellar dysfunction. It typically occurs as a
      primary infectious, post-infectious or post vaccination disorder, typically in
      early childhood. The author presents a case of recurrent, acute cerebellar ataxia
      in a 20-year-old woman. In the described case the first event of acute cerebellar
      ataxia occured at the age of 15. The disease lasted 3 weeks and symptoms
      disappeared entirely. The similar symptoms recurred after 5 years but they were
      more pronounced and accompanied by pleocytosis, high protein level and low
      glucose level in cerebrospinal fluid. The symptoms disappeared entirely after 2
      months of treatment.

PMID- 16909794
TI  - [Epidemiology of tick-borne diseases in Poland].
AB  - The paper summarizes state of art knowledge on tick-borne diseases epidemiology
      in Poland. The most prevalent diseases are Lyme borreliosis (LB) and tick-borne
      encephalitis (TBE). Although there is growing number of data published on
      anaplasmosis and babesiosis prevalence in ticks and humans, there is no national
      data on these diseases and their epidemiological features remain unclear. All
      tick-borne agents have a common vector tick--the sheep tick Ixodes ricinus. LB
      and TBE are mandatory reportable diseases. In 2005 case definitions were
      implemented in Poland to allow a better comparability of data within the country
      and with other European countries. LB is widespread in Poland. Studies of
      prevalence of infected ticks indicate that from 6 to 15% of I. ricinus ticks in
      different sites are infected with the spirochete. Data from seroepidemiologic
      studies and from routine surveillance (started in 1996) confirm that the disease
      is widespread in Poland, and its incidence is increasing. It has increased from
      2.31 per 100,000 in 1999 to 11.55 in 2005. One reason of this increase is the
      improvement in diagnosis of the disease. There is a need to promote personal
      protection during outdoor activities and knowledge on LB symptoms, especially
      among populations at risk--forestry workers, farmers. TBE incidence is limited to
      two main foci--one in the Northeast of Poland bordering Baltic states endemic
      region, and the second on the South of Poland, neighbouring the Czech and Slovak
      republics. Seroepidemiologic data, supported by surveillance data, indicate that
      there are areas of particularly high TBEV activity. The mostly affected
      occupational groups are: unemployed, retired, students, and farmers. This is a
      reason to promote personal protection and prophylactic vaccination of both
      inhabitants of endemic regions and tourists visiting endemic regions.

PMID- 16909795
TI  - [Infectious agents in the pathogenesis of multiple sclerosis].
AB  - Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous
      system (CNS) of a still unknown etiology. Genetic factors, environmental agents
      and an autoimmune response may play an important role in the pathogenesis of MS.
      In the paper the current opinion on the role of infectious agents in the
      pathogenesis of MS is presented. The results of epidemiological and serological
      studies are discussed as well as the results of viral isolation attempts and the
      search for virus structures in the CNS of MS patients. The most important
      findings in the field e.g. a potential role of Epstein-Barr virus (EBV), human
      herpesvirus 6 (HHV-6) and bacteria Chlamydia pneumoniae in MS are presented.
      Postulated mechanisms of virus-induced demyelination are also described.

PMID- 16909796
TI  - [Detection of human herpesvirus type 8 (HHV-8) in the central nervous system in
      patients from Poland].

PMID- 16909797
TI  - [New aspects of pathogenesis of Lyme borreliosis].
AB  - B. burgdorferi can evade the destructive effects of the immune system by binding
      host's complement regulators, which leads to inhibition of the complement
      activation cascade. Complement activity is blocked by CRASPs--complement
      regulator acquiring surface proteins. Complement resistance might therefore
      represent one major pathogenic factor favoring spirochete transmission to the
      vertebrate host, as well as determine host reservoirs of Borrelia burgdorferi
      genospecies. The cause of neuro-psychiatric disorders developing in some patients
      with Lyme borreliosis is still unknown. One of the hypotheses links them to neuro
      hormonal disturbances induced by B. burgdorferi infection.

PMID- 16909798
TI  - [Comparison of two types of diagnostic test detecting antibodies against Borrelia
      burgdorferi: EIA based on one genospecies antigens and ELISA based on recombinant
      antigens].
AB  - The aim of the study was to compare the results of ELISA diagnostic kit detecting
      antibodies against B. burgdorferi based on combination of three genospecies
      recombinant and EIA kits based on one of three genospecies. Sera of 351 forest
      workers were evaluated with ELISA kit (Recombinant antigen, IgG). Seropositive
      samples were tested with EIA kits based on B. burgdorferi s.s., B. garinii, B.
      afzelii antigens. Diagnostic kits based on combination of antigens of three
      genospecies more often detect antibodies against B. burgdorferi and are more
      usefull as screening tests, in comparison with those based on one genospecies.
      Among diagnostic kits based on one genospecies, the most sesnitive in detection
      of antibodies against B. burgdorferi are those based on B. afzelii.

PMID- 16909799
TI  - [Western-blot with VLSE protein and "in vivo" antigens in Lyme borreliosis
      diagnosis].
AB  - The aim of the study was the evaluation of the efficiency of Western blot
      (EcoLine) test detecting simoultanous presence of IgM and IgG antibodies against
      B. burgdorferi in diagnosis of early and late stage of Lyme borreliosis. The
      comparison of results achieved by performing test Western-blot, ELISA (based on
      recombinant antigens of three genospecies of Borrelia) and EIA (based on antigens
      of one B. burgdorferi genospecies). The tests Western blot: EcoLine (Virotech)
      with antygens "in vivo", ELISA Borrelia IgM, IgG recombinant (Biomedica), EIA: B.
      b. ss. IgG, EIA B. garinii IgG, EIA B. afzelii IgG (TestLine) were used. Results
      showed efficacy of detecting IgM, IgG antibodies against VlsE simultanously and
      IgG antibodies against "in vivo" antigens in diagnosis of early stages of Lyme
      disease when atypical picture skin lessions arise diagnostic doubts and in
      discerning early and late stage of disease. The EIA tests based on one B.
      burgdoreferi genospecies seem less effective in comparison to ELISA tests based
      on 3 genospecies antigens.

PMID- 16909800
TI  - [Tick borne encephalitis and enviromental changes].
AB  - Currently observed markedly increased incidence of various tick borne diseases in
      many parts of Europe is due to documented climatic changes as well anthropogenic
      influence on habitat structure. One of the analyzed factors is tendency to
      increase of the spring temperatures, especially in the third decade of the April.
      Such conditions (spring temperatures above 7-10 degrees C) let the nymphs and
      larvae of Ixodes ricinus to feed simultaneously on rodents. This increases the
      risk of infection of Ixodes ricinus with TBE virus, so dangerous for humans.

PMID- 16909801
TI  - [Proceedings and abstracts from the 5th Polish Educational Conference on
      Neuroinfection, Bialystok, 21-22 April 2006].

PMID- 16909802
TI  - Disclosing medical errors to patients.

PMID- 16909803
TI  - An unusual 'disappearing mass' in the ear canal.

PMID- 16909804
TI  - Endoscopic view of the ethmoid strut.

PMID- 16909805
TI  - Severe laryngeal hyperkeratosis secondaryto laryngopharyngeal reflux.

PMID- 16909806
TI  - Synovial sarcoma.

PMID- 16909807
TI  - Transsphenoidal encephalocele in a neonate.

PMID- 16909808
TI  - Solitary fibrous tumor of the carotid sheath.

PMID- 16909809
TI  - Reconstruction of the conchal bowl and external auditory canal.

PMID- 16909810
TI  - Modifier 78.

PMID- 16909811
TI  - Assessment of patient satisfaction with various configurations of digital CROS
      and BiCROS hearing aids.
AB  - We conducted a study of 91 patients with severe-to-profound asymmetric hearing
      loss to assess their satisfaction with digital contralateral routing of signal
      (CROS) or bilateral contralateral routing of signal (BiCROS) hearing aids,
      Satisfaction was evaluated on the basis of the number of patients who elected to
      purchase their hearing aid following a free 30-day trial and on the results of a
      subsequent 8-question survey. We found that overall patient satisfaction was
      generally high. At the end of the 30-day trial, 66 of the 91 patients (72.5%)
      elected to keep their CROS or BiCROS device, a percentage that is far greater
      than the acceptance rates of 10 to 20% that had been previously reported with
      older models of the CROS and BiCROS devices. According to the survey responses,
      those who kept their devices gave them an overall rating of 3.4 on a scale of 1
      (very dissatisfied) to 5 (very satisfied); those who returned their devices gave
      them an overall rating of 1.9.

PMID- 16909812
TI  - Development of nasal skin necrosis associated with rituximab treatment for
      Waldenstrom's macroglobulinemia and subsequent spontaneous resolution.
AB  - We report the unusual case of a 72-year-old man who developed acute and extensive
      necrosis of the nasal skin and soft-tissue envelope while undergoing chemotherapy
      for Waldenstrom's macroglobulinemia, a lymphoproliferative disorder The patient's
      treatment involved infusions of rituximab, a chimeric monoclonal antibody that is
      directed against B cell surface membrane protein CD20. The patient refused
      surgery to restore the nose, and he was treated conservatively with wet-to-dry
      dressings and antibiotic ointment. Approximately 5 weeks after admission, the
      eschar had exfoliated, revealing that the underlying skin was pink and healthy;
      no significant areas of necrosis remained. Within weeks, the nose had healed
      completely without scarring. A good aesthetic result was achieved exclusively
      through healing by secondary intention. We wish to alert the medical community
      that (1) conservative management of even extensive nasal skin loss should be
      considered when clinically acceptable, and (2) there may be an association
      between anti-CD20 antibody therapy for Waldenstrom's macroglobulinemia and skin
      necrosis.

PMID- 16909813
TI  - Extramedullary plasmacytoma of the nasal cavity: treatment perspective in a
      developing nation.
AB  - Extramedullary plasmacytomas are uncommon tumors, with a worldwide annual
      incidence of 3 per 100,000 population. They account for 1% of all tumors of the
      head and neck and 4% of all nonepithelial tumors of the nasal tract. A variety of
      treatment options has been suggested. These treatments vary according to the site
      of presentation, the presence of locoregional spread, and the histologic picture.
      Radiotherapy has been widely used as a treatment modality, but little has been
      written about surgery as a single management modality. However, such an option
      assumes importance in a developing nation, where patient follow-up is erratic and
      treatment costs must be kept low. We discuss the feasibility of surgery in such a
      circumstance, and we describe our surgical treatment of a case of extramedullary
      plasmacytoma in an elderly woman who presented to our hospital in India.

PMID- 16909814
TI  - Solitary fibrous tumor of the floor of the mouth: case report and review of the
      literature.
AB  - Solitary fibrous tumor is an uncommon spindle cell neoplasm that is believed to
      be of mesenchymal origin. Rarely does it originate in the oral cavity, and only 1
      case of this lesion in the floor of the mouth has been previously reported. We
      describe a new case of solitary fibrous tumor arising from the soft tissues of
      the floor of the mouth.

PMID- 16909815
TI  - Sialoblastoma: a rare submandibular gland neoplasm.
AB  - A sialoblastoma is a rare congenital epithelial tumor that arises in a major
      salivary gland. To our knowledge, only 24 cases of sialoblastoma have been
      previously reported in the English-language literature. We report a new case,
      that of a 15-month-old boy who presented with a submandibular mass. Surgical
      excision of the mass was undertaken. Intraoperatively, the mass appeared to be
      adjacent to the submandibular gland, but it had not invaded it. The mass was
      excised, and the submandibular gland was left in place. Pathology identified the
      tumor as a sialoblastoma. However, pathology also revealed that residual tumor
      was present at the surgical margin. The patient was returned to the operating
      room for excision of the left submandibular gland and the level I lymph nodes.
      Following revision surgery, the surgical margins were negative. The patient
      remained disease-free at the 1-year follow-up. Despite the need for revision
      surgery, this case provides support for the idea that surgery alone is sufficient
      for curative treatment.

PMID- 16909816
TI  - Three-dimensional computed tomography and surgical treatment for Eagle's
      syndrome.
AB  - Eagle's syndrome represents a group of symptoms that includes recurrent throat
      pain, globus pharyngeus, dysphagia, referred otalgia, and neck pain possibly
      caused by elongation of the styloid process or ossification of the stylohyoid or
      stylomandibular ligaments. The medical history and physical and radiologic
      examinations are the main guides to the precise diagnosis. The radiologic
      diagnostic modality of choice is three-dimensional computed tomography (3-D CT).
      We describe a case of bilaterally symptomatic Eagle's syndrome that was diagnosed
      by 3-D CT of the styloid processes and successfully treated with surgery via a
      transoral approach.

PMID- 16909817
TI  - Fibrous dysplasia in the retropharyngeal area.
AB  - More fibro-osseous lesions originate in the bones of the extremities than in the
      craniomaxillofacial bones, scapula, and ribs, which are rarely involved. Fibro
      osseous lesions that decrease the quality of life should be treated surgically.
      We report the case of a fibro-osseous lesion that caused globus pharyngeus and
      dysphagia. We discuss the clinical, radiologic, and histopathologic features of
      this case as well as the removal of this unusual lesion by Doppler ultrasound
      guided surgery. To the best of our knowledge, no other case of a fibro-osseous
      lesion in the retropharyngeal area has been reported in the literature.

PMID- 16909818
TI  - Laryngeal neurilemmoma: a case report.
AB  - Published reports of benign nerve sheath tumors of the larynx are extremely rare.
      Because these tumors represent a potential threat to the airway, prompt diagnosis
      and treatment are vital. We report a case of a neurilemmoma that arose from the
      right arytenoid muscle adjacent to the arytenoid cartilage. The mass was
      completely excised, and no recurrence was observed during follow-up. We discuss
      the diagnosis and management of this rare tumor.

PMID- 16909819
TI  - Herpes simplex virus infection presenting as a piriform sinus mass.
AB  - Evidence is accumulating that herpes simplex virus (HSV) infection is implicated
      in oncogenesis. HSV antigens have been observed in some oral cancers. We present
      the case of a 62-year-old man who presented with dysphagia, odynophagia, and
      dysphonia and who was found on computed tomography (CT) to have a mass in his
      piriform sinus. We suspected a malignancy, but histopathology of biopsy specimens
      revealed that the mass exhibited the classic signs of the HSV cytopathic effect,
      including the presence of intranuclear inclusion bodies, ballooning degeneration
      of epithelial cells, and a ground-glass appearance of some nuclei. The patient
      responded well to antiviral therapy, and posttherapy CT revealed that the mass
      had resolved completely. To the best of our knowledge, this is the first report
      in the literature of a case of HSV infection presenting as a piriform sinus mass.

PMID- 16909820
TI  - Aberrant thymus and parathyroid gland presenting as a recurrent lateral neck
      mass: a case report.
AB  - We report an interesting case of a recurrent left lateral neck mass in a 6-year
      old boy. When the tumor failed to disappear after a course of antibiotic therapy,
      it was excised. Histologic study revealed that the encapsulated mass contained a
      parathyroid gland embedded within a histologically normal thymus. The presence of
      thymic and parathyroid tissue within a single capsule supports the idea that
      these two structures have a common embryologic origin. The combination of thymic
      and parathyroid tissue in a neck mass in a patient so young is rarely reported.

PMID- 16909821
TI  - Thyroglossal duct cyst: an unusual presentation.
AB  - Most thyroglossal duct cysts are located at or very close to the midline. They
      generally manifest as painless neck swellings, and they move on protrusion of the
      tongue and during deglutition. We describe a case of thyroglossal duct cyst that
      was unusual in that the cyst was located far from the midline, it did not move on
      protrusion of the tongue, and it was associated with symptoms of dysphagia and
      extensive neck swelling that mimicked a colloid goiter

PMID- 16909822
TI  - Sinking toward a fertile chaos.

PMID- 16909823
TI  - Family medicine vs. retail medicine.

PMID- 16909824
TI  - Dressing the part.

PMID- 16909825
TI  - Medicare proposes substantial changes to physician fee schedule.

PMID- 16909826
TI  - A refresher on medical necessity.

PMID- 16909827
TI  - Finding the perfect job.

PMID- 16909828
TI  - The top PDA resources for family physicians.

PMID- 16909829
TI  - How to plan an open house for your practice.

PMID- 16909830
TI  - How does your practice measure up?

PMID- 16909831
TI  - What family physicians need to know about pay for performance.

PMID- 16909832
TI  - Diagnosis du jour.

PMID- 16909833
TI  - [Different patterns of evolution in alternative and constitutive coding regions
      of Drosophila alternatively spliced genes].
AB  - Seven hundred and ninety Drosophila melanogaster genes, alternatively spliced in
      coding regions were considered together with their Drosophila pseudoobscura
      orthologs. It was found that nucleotide substitutions in alternative coding
      regions accumulate more intensively than in constitutive regions. Moreover, the
      evolutionary pattern of alternative regions depends on their inclusion mechanisms
      (use of alternative promoters, splicing sites or polyadenylation sites)
      significantly. The rate of synonymous substitutions varies is more dramatically
      than that of nonsynonymous substitutions. Nucleotide substitution patterns in
      different classes of alternative regions of mammalian and Drosophila genes have
      little in common.

PMID- 16909834
TI  - [EDAS, databases of alternatively spliced human genes].
AB  - EDAS, a database of alternatively spliced human genes, contains data on the
      alignment of proteins, mRNAs, and EST. It contains information on all exons and
      introns observed, as well as elementary alternatives formed from them. The
      database makes it possible to filter the output data by changing the cut-off
      threshold by the significance level. The database is accessible at
      http://www.gene-bee.msu.ru/edas/.

PMID- 16909835
TI  - [Methods for improving the quality of prediction in the process of automatic
      annotating A4].
AB  - Modifications of the previously described adaptive algorithm of automatic
      annotating A4 have been considered, which make it possible to improve the quality
      of prediction. First, the direct use of the so-called basis statistics eta
      refines the quality of prediction compared with the previously proposed
      statistics gamma. Second, the quality is improved if not all similar sequences
      found but only part of them are used. This decreases the noising of the data,
      which in turn improves the quality of prognosis.

PMID- 16909836
TI  - [Interstitial telomere repeats as markers of evolutionary changes in the
      mammalian karyotype: human chromosome 2].
AB  - Telomer repeats represented by hexamer (TTAGGG)n at chromosome termini are
      required for correct function and chromosome stability. At the same time,
      interstitial telomer sequence (ITS) located far from the chromosome ends are
      known for several mammalian genomes, including the human genome. It is assumed
      that these repeats mark the points of fusion or other chromosome reconstructions
      of ancestors. Exact localization of all interstitial telomer sequences in the
      genome could greatly improve our understanding of the mechanism of karyotype
      evolution and species origin. We have developed a software for a search of
      interstitial telomer sequences in complete sequences of mammalian genomes. We
      have demonstrated the evolutionary significance of repeats by an example of human
      chromosome 2. The results and supplementary materials are available at the site
      of the Institute of Cytology and Genetics:
      http://www.bionet.nsc.ru/labs/theorylabmain/orlov/telomere/.

PMID- 16909837
TI  - [Statistical analysis of nucleosome formation sites].
AB  - The prediction of the DNA capacity to form nucleosome structure based on sequence
      statistics is of importance in the analysis of gene expression regulation in
      eukaryotes. A context analysis of nucleotide sequences of experimentally defined
      sites of nucleosome formation made it possible to determine the sequence
      preference for nucleosome formation on the basis of statistical information. An
      improved version of the Markov model was developed to predict the preference of
      DNA sequences to be within a nucleosome structure. The developed VMM (Variable
      Memory Markov model) program computes the nucleosome formation potential for
      genomic DNA sequences of arbitrary lengths, including the short transcription
      factor binding sites. Differences in nucleosome potential for exons, introns, and
      promoters were revealed. A correlation of the nucleosome potential estimate with
      text complexity was established. The VMM is available at http://wwwmgs.
      bionet.nsc.ru/programs/VMM/.

PMID- 16909839
TI  - [Optimal relationship between average conformational entropy and average energy
      of interactions between residues for fast protein folding].
AB  - Based on the known experimental data and using the theoretical modeling of
      protein folding, we demonstrate that there exists an optimal relationship between
      the average conformational entropy and the average energy of contacts per
      residue, that is an entropy capacity, for fast protein folding. Statistical
      analysis of conformational entropy and the number of contacts per residue for
      5829 protein structures from four general structural classes (all-alpha, all
      beta, +/-/beta, alpha+beta) demonstrates that each class of proteins has its own
      class-specific average number of contacts and average conformational entropy per
      residue. These class-specific features determine the folding rates: a proteins
      are the fastest folding proteins, then follow beta and alpha+beta proteins, and
      finally alpha/beta proteins are the slowest ones.

PMID- 16909838
TI  - [Potential open reading frames within 5'-untranslated regions of eukaryotic
      mRNAs].
AB  - It is known that 5'-untranslated sequences of eukaryotic mRNA often contain AUG
      triplets, which may serve as the sites of translation initiation. It is thought
      that these leader open reading frames can fulfil the regulatory functions and
      encode functionally active proteins. However, they have been incompletely
      characterized. The article deals with the context organization of leader reading
      frames of eukaryotic mRNAs. It has been shown that their characteristics
      correlate with the position relative to the protein-encoding sequence, which may
      be associated with the efficiency of initiation of translation.

PMID- 16909840
TI  - [Method SiteGA for the recognition of transcription factor binding sites].
AB  - A new approach, SiteGA, for the prediction of functional transcription factor
      binding sites has been developed. The approach is based on the detection of
      locally positioned dinucleotides by the genetic algorithm and discriminant
      analysis. The approach has been applied to recognize transcription factor binding
      sites involved in the regulation of immune responses and cell growth (AP-1, IRF1,
      ISGF3, NFkappaB, STAT1), obesity and lipid metabolism (HNF4, PPAR, SREBP), and
      the expression of steroidogenesis genes (SF-1). SiteGA is far superior in
      accuracy to the traditionally used method of position weight matrices. The
      approach was implemented in the web tool, SiteGA http://wwwmgs2.
      bionet.nsc.ru/mgs/programs/sitega.

PMID- 16909842
TI  - [Relationship between micro- and minisatellites in the human genome].
AB  - Micro- and minisatellites constitute an essential part of DNA with a low sequence
      complexity and carry several important functions. A search for tandem repeats in
      the human genome with a length of a repeat unit of up to 70 bp, including repeats
      with a great number of nucleotide substitutions, has been performed using the
      TaadeaSWAN program. It was shown that, for a considerable number of
      minisatellites with the length of the repeating unit of less than 25 nt, a
      shorter repeating motif can be distinguished in the sequence of this repeat,
      which often is similar to the sequence of minisatellites widely occurring in the
      human genome. A model of hierarchic origination of minisatellites in the human
      genome is suggested.

PMID- 16909841
TI  - [Phylogenetic analysis of the family of p53].
AB  - A relationship between the functional significance of individual amino acid
      residues of the p53 protein, their positions in the protein structure, and the
      mode of evolution of the codons corresponding to these residues has been
      established. A phylogenetic analysis of the coding sequences of the gene of p53
      from 32 vertebrate species has been performed. It was found that those codons
      undergo selection that affect the efficiency of binding of protein p53 as a
      transcription factor. It was shown that the frequency of occurrence of generative
      mutations maintaining the normal function of the protein in conservative codons
      differs statistically significantly from the frequency of occurrence in the same
      codons of mutations with the effects of loss and acquisition of the function, and
      the negatively dominant effect. The phylogenetic analysis and molecular dynamics
      modeling made it possible to obtain evidence for the functional significance of
      the G245 residue for which the appearance of the binding site for Zn2+ in the
      case of the substitution G245G has previously been proposed.

PMID- 16909843
TI  - [InterPro as a new tool for whole genome analysis. A comparative analysis of
      Mycobacterium tuberculosis, Bacillus subtilis and Escherichia coli as a case
      study].
AB  - InterPro was developed as a new integrated documentation resource for protein
      families, domains and functional sites to rationalize the complementary efforts
      of the PROSITE, PRINTS, Pfam and ProDom database projects and has applications in
      computational functional classification of newly determined sequences lacking
      biochemical characterization and in comparative genome analysis. InterPro
      contains over 3500 entries, with more than 1000000 hits in SWISS-PROT and TrEMBL.
      The database is accessible for text- and sequence-based searches at
      http://www.ebi.ac.uk/interpro/. InterPro was used for whole proteome analysis of
      the pathogenic microorganism, Mycobacterium tuberculosis, and comparison with the
      predicted protein coding sequences of the complete genomes of Bacillus subtilis
      and Escherichia coli. 64.8% of the M. tuberculosis proteins in the proteome
      matched InterPro entries, and these could be classified according to function.
      The comparison with B. subtilis and E. coli provided information on the most
      common protein families and domains, and the most highly represented families in
      each organism. InterPro thus provides a useful tool for global views of whole
      proteomes and their compositions.

PMID- 16909844
TI  - [Heteroassociation of antibiotic norfloxacin with aromatic vitamins in aqueous
      solution].
AB  - The heteroassociation of the antibacterial antibiotic norfloxacin with aromatic
      vitamins nicotineamide and flavin mononucleotide in aqueous solution has been
      studied by 1H NMR spectroscopy (503 MHz). Equilibrium constants, induced proton
      chemical shifts, and the thermodynamic parameters (deltaH, deltaS) of the
      heteroassociation of molecules were determined from the concentration and
      temperature dependences of chemical shifts of protons of interacting aromatic
      molecules. An analysis of the results indicates the formation of heterocomplexes
      between the molecules of the vitamins and norfloxacin, which is caused by
      stacking interactions between aromatic chromophores and an additional
      intermolecular hydrogen bond in the norfloxacin-nicotinamide system. Based on the
      analysis of induced chemical shifts of protons of molecules, the most probable
      spatial structures 1:1 of norfloxacin-flavin mononucleitide and norfloxacin
      nicotinamide heterocomolexes were determined by the methods of molecular modeling
      using the X-PLOR program.

PMID- 16909845
TI  - [Conformers of carnosine].
AB  - The geometric and energetic parameters of most stable conformations of carnosine
      were calculated by the semiempirical guantum-chemical method PM3. The carnosine
      water-zinc (II) clusters were simulated.

PMID- 16909846
TI  - [Biophysical aspects of reconstruction of a single cell by the methods of cell
      engineering].
AB  - The problems of a low efficiency of mammalian cloning are discussed with emphasis
      on the necessity of the expertise of each step of single cell reconstruction,
      beginning with microsurgical manipulations. The fact of cell content leakage when
      the cell is held during microsurgery or microinjections with the help of the
      conventional method using negative pressure in the holding micropipette was
      demonstrated in experiments on murine embryos. It was shown that the rate of cell
      content efflux depends on the value of negative pressure generated in the holding
      micropipette, and is directly proportional to the dimensions of its orifice and
      the duration of micromanipulations. An alternative method of cell fixation using
      the capillary forces of the holding micropipette was proposed. The method
      optimizes the process of cell fixation, reducing the holding effort by two orders
      of magnitude. As a result, 92% of embryos remain viable after fixation of embryo,
      as compared with 39% in the conventional technique. In order to diminish the cell
      damage produced by the tip of a microinstrument, a new technique of fabricating
      micropipettes was proposed. The improved method of filling the micropipette with
      viscous liquids, including DNA, which is described in details in the paper,
      enabled constant (non-stop) microinjection of more than 1000 cells by hand,
      without any special automatic device.

PMID- 16909847
TI  - [Molecular dynamics modeling of the substitution of serine for the conservative
      glycine in the G loop in the yeast cdc28-srm mutant using the crystalline lattice
      of human kinase CDK2].
AB  - Two-nanosecond molecular dynamics modeling of the crystalline lattice of an
      active complex of kinase pT160-CDK2/cyclin A/ATP-Mg2+ substrate has been
      performed. The results of modeling indicated that the structures of the nonmutant
      CDK2 complex and mutant CDK2 complex, which involves the G 16S-CD K2 substitution
      corresponding to that of yeast, markedly differ, the differences in structural
      conformations being particularly well pronounced in those regions that play a key
      role in the functioning of kinase. Based on the results of computations,
      structural elements are considered that may affect the kinase activity and
      regulatory phosphorylation, and the binding of protein kinase to cyclins and
      substrates.

PMID- 16909848
TI  - [Proteins associated with mitochondrial DNA protect it against the action of X
      rays and hydrogen peroxide].
AB  - It has been suggested in a number of investigations that the high vulnerability
      of mitochondrial DNA to reactive oxygen species and other damaging agents is due
      to the absence in mitochondria of histones complexed with DNA. In the present
      study it was shown that DNA-binding proteins of mitochondrial nucleoids were able
      to shield mitochondrial DNA from X-ray radiation and hydrogen peroxide, as
      nuclear histones did. Mitochondria, mitochondrial nucleoid proteins, and histones
      were isolated from mouse liver cells. The degree of damage to or protection of
      mitochondrial DNA was assessed from the yield of its PCR amplification product.
      The in vitro experiments demonstrated that mouse mitochondrial DNA, when in
      complex with mitochondrial nucleoids or nuclear histones, was damaged much less
      by radiation and/or hydrogen peroxide than in the absence of these proteins and
      histones. No significant difference between mitochondrial nucleoid proteins and
      nuclear histones was revealed in their efficiency to protect mitochondrial DNA
      from the damaging effect of radiation and hydrogen peroxide. It is likely that
      the nucleoid proteins in the mitochondria shield mitochondrial DNA against the
      attack of reactive oxygen species, thus significantly decreasing the level of the
      oxidative damage to mitochondrial DNA.

PMID- 16909849
TI  - [Energy distribution and ionic selectivity of the bacterial potassium channel].
AB  - An explanation for the ionic selectivity of the bacterial potassium channel
      K(CS)A is offered, which is based on a comparison of energy interactions of
      lithium, sodium, and potassium cations with the atoms of the selective filter of
      an protein pore. Using quantum-chemical calculations, the presence of a deeper
      potential hole for potassium ions was discovered, which explains the energy
      preferableness in their permeability. It has been shown that the traditional
      methods of force field AMBER, CHARMM, OPLS in reference parametrization and also
      at their partial reparametrization give incorrect ratings of energy distribution
      of ions in the channel.

PMID- 16909850
TI  - [Proton transfer via the external proton channel of bacteriorhodopsin].
AB  - The process of proton transfer across the membrane via the external proton
      channel in bacteriorhodopsin is considered. A possible amino acid composition of
      the channel is suggested and the step-by-step mechanism of proton transfer is
      proposed which agrees with the experimental data. The rate of proton transfer
      between fixed centers at several chains of the channel was estimated for which
      the spectroscopic data are available.

PMID- 16909851
TI  - [Spectral characteristics and the structure of chloroplasts upon blocking the
      early stages of chlorophyll biosynthesis].
AB  - The cotton mutant xantha (Gossypium hirsutum L.) with the blocked synthesis of 5
      aminolevulinic acid in the light has been shown to accumulate chlorophyll 30
      times less than the parent type. In chloroplasts of the mutant xantha, the
      formation of the membrane system is blocked at the earliest stages, mainly at the
      stage of bubbles and single short thylakoids. Only light-harvesting chlorophyll
      a/b-protein complexes I and II with chlorophyll fluorescence maxima at 728 and
      681 nm, respectively, are formed in plastid membranes of the mutant. It has been
      concluded that the genetic block of chlorophyll biosynthesis in the mutant xantha
      disturbs the formation and functioning of the complexes in reaction centers of PS
      I and PS-II, inhibiting the development of the whole membrane system of
      chloroplasts at the stage of bubbles and single thylakoids.

PMID- 16909852
TI  - [Dependence of dielectrophoretic force on the size of cylindrical particles by
      the example of a suspension of erythrocytes].
AB  - For the modeling of erythrocyte rouleaux (linear cell aggregations), we propose
      an approximation procedure for the dipole moment in short cylinders, which
      contains the case of ellipsoidal bodies only as a first approximation. The method
      allows one to introduce corrections that are more representative for these
      particles. Depending on the number of erythrocytes forming an aggregation, i.e.,
      on different but discrete measures of rouleaux lengths, the dielectrophoretic
      force is calculated and represented against the frequency of the applied a.c.
      field. As a result, frequency regions in the upper MHz range appear in which the
      strength and direction of DEP forces are different for different rouleaux sizes.
      This property is suitable for the detection and spatial separation of rouleaux
      populations of different length in blood samples by means of a microelectronic
      array.

PMID- 16909853
TI  - [Modeling of intraorgan arterial vasculatures. I. A stationary blood flow at low
      Reynolds numbers].
AB  - Based on the statistical relationships between the lengths and diameters of
      vessels in the arterial beds, obtained by measurements on plastic casts, a method
      for the generation of models of intraorgan arterial vasculatures was proposed.
      The dependence of the total hydraulic conductivity of the system on the model
      parameters was computed. The problem of selecting the adequate models by a
      comparison of the corresponding biophysical characteristics of vasculatures is
      discussed.

PMID- 16909854
TI  - [Modeling of processes of heat transfer in whole-body hyperthermia].
AB  - The method of whole-body hyperthermia in which the body temperature for a short
      time reaches values up to 43-44 degrees C holds currently much promise. However,
      at body temperatures above 42 degrees C, the risks associated with the
      hemodynamic instability and the appearance of arrhythmia in the patient increase.
      A model of heat transfer has been created to increase the efficiency and safety
      of the immersion-convectional method of whole-body hyperthermia. This model takes
      into account changes in the skin blood flow and the dynamics of pulse rate
      depending on body temperature. The model of heat transfer adequately reflects
      processes of heating of the organism and can form a basis for the calculation of
      distribution of heat inside the organism.

PMID- 16909855
TI  - [Biological structures as photonic objects].
AB  - Samples of the material of mollusks bowls, peacock wing elements, and human horn
      skin have been investigated using the methods of spectroscopy, atomic-force
      microscopy, X-ray diffraction analysis, and thermoconductance. Ordered
      superstructures were revealed in these objects. Evidence for effective
      interactions of both electromagnetic and electronic waves with these structures
      was obtained. It was shown that the interaction with electromagnetic waves
      reveals photonic properties and the interaction with electronic waves, the
      semiconducting properties of biological objects.

PMID- 16909856
TI  - [Inertial forces during muscle contractions as a factor compensating for the
      insufficiency of gravitation influence].
AB  - An idea has been advanced that inertial forces emerging during active movements
      are able to compensate for the deficiency of weight. The idea is based on the
      conception that these forces are by their effect on biological objects analogous
      to gravity forces. Training facilities have been developed, and tentative
      estimations have been made. The definition of "inertial massage" is introduced.

PMID- 16909857
TI  - [Transport processes of fluid exchange in the crystalline lens of the rabbit
      eye].
AB  - Processes of fluid exchange in the crystalline lens of the rabbit eye were
      investigated. The direction of movement of fluid in the crystalline lens was
      investigated from the movement of fluorescein by the method of "stopped
      diffusion". It has been found that the mechanism of fluid transport in the
      crystalline lens is active and is carried out by means of the Na-kappa-ATPase
      transport system. The energy necessary for the active transport of fluid inside
      the crystalline lens is in the range (1.5-6) x 10(-2) J. Owing to the active
      fluid transport, the pressure inside the crystalline lens constantly increases by
      6 mm Hg. In rabbit's life-time, the movement of fluid in the crystalline lens
      occurs in the direction from the anterior to the posterior surface followed by
      the exit to vitreous humor.

PMID- 16909858
TI  - [A simple model based on the first principles].
AB  - A simple model based on the first principles is proposed, which describes the
      reduplication of a molecular structure as a sequence of stages with probabilities
      that can be estimated on the basis of the general theory of molecular
      transformations. It is demonstrated that the reproduction of genetic information
      in time (life phenomenon) over a long period is impossible without the
      simultaneous "death effect". Taking into account the peculiarities of transient
      states (quantum beats) leads to the appearance of self-oscillations.

PMID- 16909859
TI  - [Structure-activity relationships in a series of semisynthetic polycyclic
      glycopeptide antibiotics].
AB  - The main achievements in the development of methods for the design of
      semisynthetic antibiotics of a new generation belonging to the group of
      polycyclic glycopeptides directed against infections caused by multidrug
      resistant bacteria and dangerous human and animal viruses are reviewed. The
      review is focused on the results obtained at the Gauze Institute in the area of
      chemical modification of natural antibiotics (eremomycin, vancomycin,
      teicoplanin, etc.) directed toward modification of their antibacterial and/or
      antiviral activity. A special emphasis is placed on the study of the mechanisms
      of action of these antibiotics, which could be the basis of a rational approach
      to their chemical modification involving the transformation of the inner binding
      pocket and the peripheral regions of the molecules that participate in the
      formation of their complexes with targets. The study of the recently discovered
      antiviral activity of modified glycopeptide antibiotics is also discussed. A
      possibility of obtaining new highly active anti-HIV-1 and anti-HIV-2 preparations
      on the basis of hydrophobic derivatives of the aglycones of glycopeptide
      antibiotics was demonstrated. New semisynthetic derivatives of antibiotics that
      exhibit a high antibacterial activity in vivo, have good pharmacological
      characteristics, and are promising for practical use are described.

PMID- 16909860
TI  - [Monolithic stationary phases: yesterday, today, and tomorrow].
AB  - The history of the development of monolithic stationary phases in chromatography,
      the modem state of the art, and the prospects for their use are considered.

PMID- 16909861
TI  - [Structure and function of pore-forming proteins from bacteria of the genus
      Yersinia: I. Isolation and a comparison of physicochemical properties and
      functional activity of Yersinia porins].
AB  - The molecular organization and functional activity of porins isolated from the
      outer membrane (OM) of the Yersinia enterocolitica and three phylogenetically
      close nonpathogenic Yersinia species (Y. intermedia, Y. kristensenii, and Y.
      frederiksenii) cultured at 6-8 degrees C were comparatively studied for the first
      time. The proteins were isolated in two molecular forms (trimeric and monomeric),
      and their spatial structures were characterized by the methods of optical
      spectroscopy, CD and intrinsic protein fluorescence. The studied porins were
      shown to belong to the beta-structural proteins (they have 59-96% total beta
      structures and 0-17% alpha helices). The spatial structures of the proteins were
      demonstrated to depend on the nature of the detergent used for solubilization.
      Unlike the enterobacterial pore-forming proteins, the porin trimers are less
      stable to sodium dodecyl sulfate (SDS). The spatial structures of the porins
      become more compact after the substitution of octyl beta-D-glucoside for SDS: the
      content of beta structures increases and the accessibility of Trp residues to
      solvent decreases. It was established with the use of the technique of bilayer
      lipid membranes that the functional properties of the porins are similar to those
      of the OmpF proteins of Gram-negative bacteria. Trimers are functionally active
      forms of the porins. Special features of the pore-forming activity of the
      Yersinia porins were revealed to depend on the microorganism species and the
      value of the membrane potential.

PMID- 16909862
TI  - [Fibrinolytic and fibrinogenolytic effects of acyl urokinase and urokinase
      combinations in vitro].
AB  - The in vitro thrombolytic and side effects of double-strand urokinase-type
      plasminogen activator (tcu-PA), p-guanidinobenzoyl tcu-PA (GB-tcu-PA), and their
      combinations were compared. The reversible blocking of the active site stabilizes
      GB-tcu-PA in human plasma and results in longer thrombolysis and lesser side
      effects than those of tcu-PA. However, the acylated activator displays a marked
      lag period of thrombolytic action. GB-tcu-PA and tcu-PA combinations (molar
      ratios 4 : 1 and 1 : 1) induce a prolonged and effective thrombolysis without the
      initial lag period at a low level of plasminogen, fibrinogen, and alpha2
      antiplasmin depletion in the plasma surrounding the clot.

PMID- 16909863
TI  - [Flavonoids as effective protectors of urease from ultrasonic inactivation in
      solutions].
AB  - Inactivation of soybean urease in aqueous solution at pH 5.4, 36 degrees C, and
      high-frequency sonication (2.64 MHz, 1.0 W/cm2) is substantially reduced in the
      presence of seven structurally different flavonoids. A comparative kinetic study
      of the effect of these flavonoids on the effective first-order rate constants
      that characterize the total (thermal and ultrasonic) inactivation k(i), thermal
      inactivation k(i)*, and ultrasonic inactivation k(i)(US) of 25 nM enzyme solution
      was carried out. The dependences of the three inactivation rate constants of the
      urease on the concentrations of flavonoids within the range from 10(-11) to 10(
      4) M were obtained. The following order of the efficiency of the flavonoids used
      in respect of the urease protection from ultrasonic inactivation was found:
      astragalin > silybin > naringin > hesperidin > quercetin > kaempferol > morin.
      The results confirm a significant role in the inactivation of the urease of HO*
      and HO2*, free radicals, which are formed in the ultrasonic cavitation field.

PMID- 16909865
TI  - [Noncoding sequences of the eukaryotic genome as an additional protection of
      genes from chemical mutagens].
AB  - A quantitative model was developed that detects a new function of noncoding
      sequences in the eukaryotic genome, namely, the protection of coding sequences
      from chemical (mainly endogenous) mutagens. It was shown that, under common
      ecological conditions, the number of nucleotides damaged by mutagens in coding
      sequences of the genome is inversely proportional to the size of their noncoding
      counterparts. Noncoding sequences can differently protect single genetic loci
      from chemical mutagens by the formation of specific spatial structures of the
      protected loci in the interphase nuclei. The significant differences in genome
      sizes between species (paradox C) can be explained by different contributions of
      noncoding sequences to the total effect of genome protection from endogenous
      chemical mutagens.

PMID- 16909864
TI  - [Neuroprotective effect of the hexapeptide HLDF-6 on neurons of rat hippocampus
      on the model of Alzheimer's disease in vivo and in vitro].
AB  - The neuroprotective effect of Thr-Gly-Glu-Asn-His-Arg hexapeptide (HLDF-6), a
      biologically active fragment of the differentiation factor of human leukemia
      cells (HLDF), was demonstrated on models of Alzheimer's disease in vivo and in
      vitro. The syndromes of this pathology were induced in male rats by
      administration of the peptide corresponding to the 25-35 sequence of beta-amyloid
      peptide (25-35) and ibotenic acid into the hippocampus. HLDF-6 prevented loss of
      long-term memory and decrease in the orientation-investigation activity of these
      animals and significantly decreased the number of pyknotic neurons in the CA1
      area of the hippocampus. This peptide also exerts a protective effect in vitro on
      the primary cultures of neurons of the hippocampus and cerebellum of rats under
      conditions of the beta-amyloid toxicity. An increase in the dihydrotestosterone
      (DHT) content was demonstrated in the blood plasma of rats with the syndrome of
      Alzheimer's disease and in the medium of the culture of hippocampus neurons in
      the presence of the Abeta(25-35) peptide. HLDF-6 inhibited this increase in both
      cases. A probable mechanism of the neuroprotective effect of HLDF-6 was suggested
      as being connected to its possible effect on both the biosynthesis and the
      metabolism of sex steroid hormones.

PMID- 16909866
TI  - [Promoters of genes MTHFR from patients with hyperhomocysteinemia and PTEN from
      patients with malignant and benign endometrial and ovarian tumors].
AB  - Mutational changes in the promoter regions of MTHFR genes from patients with
      hyperhomocysteinemia and PTEN genes from patients with endometrial and ovarian
      tumors were studied. An increased level of homocysteine was found in a part of
      the patients with a heterozygous C677T mutation in the MTHFR gene, although a
      moderate hyperhomocysteinemia is usually associated with homozygous mutation. We
      hypothesized that, in this case, the allele lacking the C677T mutation may be
      inactivated by the promoter mutation. The sequencing of both DNA strands of the
      minimal promoter region of the MTHFR gene in ten patients did not reveal any
      mutation, which implied another mechanism of the development of
      hyperhomocysteinemia in these patients. A PCR analysis of the minimal promoter
      region of the tumor suppressor PTEN in the presence of 2-pyrrolidone in 101
      patients from Moscow clinics revealed changes in it in patients with endometrial
      (56%) or ovarian (29%) cancer, as well as in patients with endometrial
      hyperplasia and benign ovarian tumors (34.6 and 29%, respectively). It was
      presumed that the found PTEN gene promoters may arise from epigenetic alterations
      (erroneous methylation) or may (more rarely) be induced by mutations. As a result
      of the studies, new molecular markers associated with endometrial and ovarian
      tumors were revealed and a simple and effective method of detection of these
      markers was developed.

PMID- 16909867
TI  - [Synthesis and protective anti-infective action of anomeric lipophilic glycosides
      of N-acetylmuramyl-L-alanyl-D-isoglutamine].
AB  - Anomeric pairs of alpha- and beta-dodecyl, alpha- and beta-(1-pentylhexyl), and
      alpha- and beta-cyclododecyl glycosides of N-acetylmuramyl-L-alanyl-D
      isoglutamine (MDP) were synthesized. The starting beta-D-glucosaminides were
      obtained by the oxazoline method, and the corresponding alpha-isomers, by the
      mercuric iodide-catalyzed glycosylation of alcohols with alpha-glucosaminyl
      chloride peracetate in nitromethane at -90 degrees C. No reliable differences
      between the stimulation of mouse resistance to the infection with Staphylococcus
      aureus (doses of 2, 20, and 200 microg/mouse) and Escherichia coli (doses of
      0.05, 1, and 20 microg/mouse) with the MDP alpha- and beta-glycosides were found.

PMID- 16909868
TI  - [The study of the reaction of terminated oligomerization in the synthesis of
      oligo-(beta1-6)-glucosamines].
AB  - The applicability of terminated oligomerization to the synthesis of oligo-(beta1
      6)-glycosamines, fragments of the intercellular polysaccharide adhesin of
      staphylococci, was studied. The reactions of terminated oligomerization were
      carried out with mono-, di-, and trisaccharide monomers and N-protected
      aminopropanol; and spacered mono- and disaccharides as terminating molecules were
      also attempted. The primary formation of cyclic products of monomer
      intramolecular glycosylation was observed in almost all the reactions. Only the
      experiments with the monomer based on the disaccharide bromide under the
      conditions of the Helferich reaction led to reduced yields (30%) of the cyclic
      products. However, even in this case, the desired terminated oligosaccharides
      were generated in approximately 10% yield and mainly were the products of single
      glycosylation of the terminator by the monomer. These experiments allow the
      conclusion that, under the examined conditions, the reaction of terminated
      oligomerization could not result in the synthesis of oligoglucosamines with a
      high molecular mass.

PMID- 16909869
TI  - [A convenient method of isoflavonone synthesis].
AB  - Reaction of 2-hydroxydeoxybenzoins with bis(dimethylamino)methane in ethanol
      results in isoflavonones.

PMID- 16909870
TI  - [A synthesis of cinnamoyloxyisoflavones].
AB  - Interaction of 7-hydroxyisoflavonones with cinnamoyl chloride results in
      cinnamoyloxyisoflavonones.

PMID- 16909871
TI  - Cancer incidence in the U.S. Air Force: 1989-2002.
AB  - BACKGROUND: Cancer incidence in U.S. Air Force active duty (AFAD) personnel is
      unknown. Defining the epidemiology may support more effective prevention and
      clinical services. METHODS: Standardized incidence ratios (SIRs) for invasive
      cancer in AFAD personnel during 1989-2002 were determined using U.S. national
      incidence rates as the reference. SIRs were adjusted for age and race. Cutaneous
      squamous and basal cell carcinomas (CAs) were excluded. RESULTS: There were 2750
      cases: 1986 in men and 764 in women. The all-cancers SIRs were for men, 0.50 (95%
      CI: 0.48-0.53), and for women, 0.96 (95% CI: 0.89-1.03). Among men, the 10 most
      frequent cancers (77.6% of total) were, in descending order: melanoma; testicular
      CA; prostate CA; non-Hodgkin lymphoma; follicular/papillary thyroid CA; Hodgkin's
      Disease; colorectal CA; brain neuroepithelial CA; and (tied) bladder CA and oral
      squamous cell CA. Among women, the 10 most frequent cancers (88.1% of total)
      were, in descending order: breast CA; cervical CA; follicular/papillary thyroid
      CA; melanoma; Hodgkin's Disease; colorectal CA; (tied) non-Hodgkin lymphoma and
      ovarian epithelial CA; vulvar CA; and (tied) brain neuroepithelial CA and oral
      squamous cell CA. Compared with the U.S. population, cancer type-specific SIRs
      were significantly increased for cervical CA, prostate CA, and vulvar CA (range,
      1.44-3.54). SIRs were significantly decreased for bladder CA (men), brain
      neuroepithelial CA, colorectal CA (men), Hodgkin's Disease (men), non-Hodgkin
      lymphoma, oral squamous cell CA (men), and testicular CA (range, 0.31-0.68). The
      remaining SIRs were not significantly different from unity. CONCLUSIONS: The
      cancer experience of the AFAD population differs substantially from that of the
      U.S. population.

PMID- 16909872
TI  - Nitrogen load in rats exposed to 8 ATA from 10-35 degrees C does not influence
      decompression sickness risk.
AB  - INTRODUCTION: Environmental temperature is commonly thought to modulate
      decompression sickness (DCS) risk, but the literature is mixed regarding which
      conditions elicit the greatest risk. If temperature is a risk factor, then
      managing thermal exposure may reduce DCS incidence. We analyzed whether hot or
      cold conditions during or immediately after a hyperbaric exposure altered DCS
      incidence in a rat model. METHODS: Rats (eight groups of five animals in each of
      nine conditions; mean body mass +/- SD = 259.0 +/- 9.2 g) were placed in a dry
      chamber that was pressurized with air to 70 m (8 ATA) for 25 min, followed by
      rapid (< 30 s) decompression under a series of temperature conditions (35
      degrees, 27 degrees, or 10 degrees C during compression; 35 degrees, 20 degrees,
      or 10 degrees C post-decompression). Animals were observed for 30 min post
      decompression for signs of DCS. DCS incidence in the 27 degrees C compression/20
      degrees C post-decompression group was 50% by design. Data from all nine groups
      of paired temperature conditions were compared with each other using analysis of
      variance, Chi-square tests, and logistic regression. RESULTS: No significant
      differences in DCS incidence were found among the groups (30-52.5% DCS incidence
      per group, 42% DCS incidence overall). DISCUSSION AND CONCLUSIONS: This animal
      model emphasized potential temperature effects attributable to tissue N2 load
      acquired during compression; there was no evidence that environmental temperature
      from 10-35 degrees C during or post-dive modulated DCS incidence. It remains to
      be determined if temperature modulates DCS risk as a function of variable N2
      elimination rates.

PMID- 16909873
TI  - Ventilatory effects of prolonged hyperoxia at pressures of 1.5-3.0 ATA.
AB  - INTRODUCTION: It was hypothesized that long-duration exposures to toxic levels of
      hyperoxia would have effects on respiratory control function or activity.
      METHODS: Ventilatory parameters of human subjects breathing spontaneously at rest
      were measured before, during, and after hyperoxia in a study of organ systems'
      tolerance to toxic O2 exposures at 1.5 ATA (17.7 h), 2.0 ATA (9.3 h), 2.5 ATA
      (5.7 h) and 3.0 ATA (3.5 h). RESULTS: Average neurotoxic changes in ventilatory
      parameters during and after prolonged hyperoxia were mild. They included: 1)
      timing component of ventilation decreased progressively with exposure duration at
      all four O2 pressures, slopes increased with O2 pressure, changes were
      significantly late in exposure at 1.5 ATA (-11%) and 3.0 ATA (-10%); 2) post-O2
      exposure respiratory rates were significantly above controls by 15% to 59%; and
      3) ventilation increased significantly by 20% late during the 1.5 ATA O2
      exposures. There were severe neurotoxic changes prior to occurrence of an "O2
      convulsion" at 3.0 ATA in one subject. Expiratory time increased by 184%;
      resultant reductions in respiratory rate and ventilation caused respiratory Pco2
      increase, accelerating rate of brain O2 poisoning. Significant nontoxic
      physiological hyperventilation (21% to 45% above control) early in hyperoxia at
      all exposure pressures persisted throughout hyperoxia, and reversed post-O2
      exposure. Hyperventilation increased and end-tidal Pco2 decreased as inspired PO2
      increased. Changes reached maximum values at approximately 2.0 ATA. DISCUSSION:
      Hyperoxia has concurrent toxic and physiological effects on respiratory control;
      degrees depend on O2 dose (exposure pressure and duration).

PMID- 16909874
TI  - Rotation velocity change and motion sickness in an optokinetic drum.
AB  - BACKGROUND: Stationary subjects who view the interior of an optokinetic drum
      often experience motion sickness (MS) symptoms, perhaps because visual and
      vestibular sensory inputs are in conflict. It was predicted that intermittently
      changing drum rotation velocity would cause an increase in sensory conflict, and
      subsequently lead to more MS. Visual input indicating frequent changes in self
      motion would not be consistent with vestibular input indicating no self-motion.
      When drum rotation is steady, visual and vestibular inputs are more likely to
      agree given that the vestibular organs only respond to change. METHODS: There
      were 12 individuals who participated in the experiment (7 men, 5 women, mean age
      = 24.0 yr). In two conditions subjects viewed the interior of an optokinetic drum
      that steadily rotated at either 5 RPM or 10 RPM. In a third condition drum
      velocity alternated every 30 s between 5 RPM and 10 RPM (5/10 RPM condition). In
      all conditions the subject's head was immobilized in the center of the drum that
      rotated on an Earth-vertical axis. Subjects completed the Simulator Sickness
      Questionnaire (SSQ) designed by Kennedy and colleagues both before a trial and
      after 4 min of drum viewing. A total SSQ score and three SSQ sub-scores (nausea,
      oculomotor, and disorientation) were obtained. RESULTS: Mean post-treatment total
      SSQ scores (mean = 41) were significantly the highest in the 5/10 RPM condition
      followed by the conditions of steady rotation velocity at 10 RPM (mean = 36) and
      5 RPM (mean = 24). Likewise, mean nausea sub-scores were also the highest (mean =
      24) in the 5/10 RPM condition followed by the 10 RPM condition (mean = 19) and
      the 5 RPM condition (mean = 11). CONCLUSIONS: These results support the
      hypothesis that a conflict between sensed and expected effects of self-motion
      alone can lead to MS. Changing rotation velocity increases sensory conflict that
      in turn leads to more MS.

PMID- 16909875
TI  - A latent class model to assess error rates in diagnosis of altitude decompression
      sickness.
AB  - BACKGROUND: Prospective testing of denitrogenation protocols to reduce the risk
      of decompression sickness (DCS) in astronauts requires pre-defined accept and
      reject criteria. We assume that the end-point of a test, the presence or absence
      of signs and symptoms attributable to DCS, is unequivocal. However, diagnosis of
      DCS is not perfect, nor is there is a gold standard to assess diagnosis error
      rates. These error rates could cause consistent bias in the decision to accept or
      reject proposed protocols. We used a Latent Class Model (LCM) incorporating inter
      rater agreement to estimate false-positive and negative rates of DCS diagnosis
      for each of six symptomatic (covariate) strata. METHODS: Case descriptions from
      135 reports collected since 1982 were available with 103 diagnosed as DCS
      (73.1%). There were 3 subsets of 45 descriptions that were randomly selected,
      information about the original diagnosis omitted, and were sent to 15 physicians
      (raters), all experts in altitude DCS. Subsets were diagnosed for DCS by either
      four, five, or six raters. We then used a LCM to estimate false-positive and
      false-negative error rates for the original NASA test diagnosis, even though a
      gold standard was not available. RESULTS: Estimates of false-positive rates in
      the NASA diagnoses ranged from 13% to 83% and from 1% to 32% for false-negative
      rates over the six strata of symptomatic response variables. CONCLUSIONS: Our
      findings suggest that use of current DCS diagnostic outcomes as if they were
      error free would likely produce an inflated rejection rate of acceptable
      protocols in future testing if adjustments are not made.

PMID- 16909876
TI  - Age and automation interact to influence performance of a simulated luggage
      screening task.
AB  - INTRODUCTION: An experiment examined the impact of automation on young and old
      adults' abilities to detect threat objects in a simulated baggage-screening task.
      METHOD: Younger and older adult participants viewed X-ray images of cluttered
      baggage, 20% of which contained a hidden knife. Some participants were provided
      an automated aid with a hit rate of 0.90 and a false alarm rate of 0.25. The aid
      provided assistance to participants in one of three forms: a text message that
      appeared before the stimulus image; a text message that appeared following the
      stimulus image; or a spatial cue concurrent with the stimulus image. Control
      participants performed the task with no assistance from an aid. RESULTS: Spatial
      cuing improved performance for both age groups. Text cuing improved young adults'
      performance, but had no benefit for older participants. Effects were similar
      whether the text cue preceded or followed the search stimulus itself. DISCUSSION:
      Results indicate that spatial cuing rather than text alerts may be more effective
      in aiding performance during a baggage screening task and such benefits are
      likely to occur regardless of operator age.

PMID- 16909877
TI  - Perception of cockpit environment among pilots on commercial aircraft.
AB  - Impaired cockpit environment may influence both well-being and performance of
      pilots. OBJECTIVE: To study the perception of cockpit environment among pilots,
      in relation to demographic factors, and type of aircraft (B767-300, B737-600,
      DC9/21-41, MD 81/90 series). METHODS: A standardized questionnaire was mailed to
      all pilots in one airline company; 81% participated (n = 622). All flights were
      non-smoking flights and the B767 was the only aircraft operated on
      intercontinental flights. The DC9 was the only aircraft without air
      recirculation. Multiple logistic regression analysis was applied, controlling for
      age, gender, smoking, perceived psychosocial work environment, and type of
      aircraft. RESULTS: Younger age and a history of atopy and stress due to excess
      work were the main predictors of symptom and environmental perceptions. The most
      common symptoms were fatigue (14%), facial dermal (10%), and nasal symptoms (9%).
      Common complaints on cockpit environment were dry air (53%), dust and dirt (48%),
      noise (46%), and inadequate illumination (34%). Using the DC9 as a reference
      category, Boeing 767 pilots had more fatigue (OR 19.5; p < 0.001), throat
      symptoms (OR = 4.40; p < 0.05), complaints on dry air (OR = 2.93; p < 0.01),
      stuffy air (OR = 4.60; p < 0.01), static electricity (OR = 6.39; < 0.05), and
      dust (OR = 2.01; p < 0.05). Boeing 737 pilots had more complaints on noise (OR =
      4.01; p < 0.001) and dust (OR = 1.81; p < 0.05). MD 81/90 pilots had more
      complaints on dry air (OR = 1.76; p < 0.05), dust (OR = 1.92; p < 0.05), and
      inadequate illumination (OR = 2.08; p < 0.05). CONCLUSION: Complaints on the
      cockpit environment were common and differed between different types of aircraft.
      This indicates a need to optimize the cockpit environment, e.g., increase the
      cleaning and relative air humidity.

PMID- 16909878
TI  - Asthma in military aviators: safe flying is possible.
AB  - INTRODUCTION: Asthma is considered relatively incompatible with aviation.
      Firstly, due to the risk of sudden incapacitation, and secondly, due to cold and
      dry air and other asthmogenic factors characteristic of the aviation environment.
      The medical requirements for flying fitness of asthmatic aviators are
      inconsistent between different air services, and many flight surgeons are
      unfamiliar with the recent developments in asthma management. This study aims to
      describe our experience with asthmatic aviators and to discuss the medical
      standards required for flying fitness in chronic asthma. METHODS: The records of
      all aviators diagnosed with asthma between January 1988 and September 2005 were
      reviewed. Pulmonary function tests and examination by a pulmonary disease
      specialist and flight surgeon were performed at least annually. RESULTS: Nineteen
      Israeli Air Force aviators with asthma were studied. Most were treated with
      inhaled long-acting beta agonists and corticosteroids. Disease control was
      satisfactory in more then 90%, with significant worsening in only one case. We
      had no cases of sudden incapacitation or any other safety breach. One aviator was
      grounded 23 yr after diagnosis due to deterioration in the severity of the
      disease, and another aviator was permanently grounded 1 yr after diagnosis.
      CONCLUSIONS: Adequate asthma control is readily feasible, even in the aviation
      environment. Long-term inhaled corticosteroids are effective and have few side
      effects in aviators. Our management approach to aviators with asthma appears to
      be safe and effective.

PMID- 16909879
TI  - Dose-dependent effects of hypergravity on body mass in mature rats.
AB  - INTRODUCTION: Previous reports have shown that exposure to hypergravity decreases
      rat body mass during the initial phase, with this decrease and level of gravity
      showing a dose-response relationship. The present study examined whether rate of
      body mass gain after the initial phase of exposure is attenuated by hypergravity
      in a dose-dependent manner and sought to identify any threshold. METHODS: Male 10
      wk-old rats (n = 64) were used, with 16 rats serving as 1.0-G controls, and 48
      rats exposed to hypergravity for 14 d in 4 groups (1.5, 2.0, 2.5, and 3.5 G; n =
      12 each). Body mass gain was evaluated according to slope of change in body mass
      from day 7 of exposure to hypergravity, as both absolute and relative values.
      RESULTS: Slopes of body mass gain did not differ between the 1.0- and 1.5-G
      groups (6.09 and 5.75 g x d(-1), respectively), but were significantly less for
      the 2.0-, 2.5-, and 3.5-G groups (4.91, 3.03 and 1.99 g x d(-1), respectively)
      than for the 1.0- and 1.5-G groups. Body mass gain as a relative value did not
      differ between the 1.0-, 1.5-, and 2.0-G groups (1.5 +/- 0.2, 1.6 +/- 0.6 and 1.4
      +/- 0.3 g x d(-1) x 100 g(-1) body mass, respectively), but was significantly
      less for the 2.5- and 3.5-G groups (1.1 +/- 0.6 and 0.8 +/- 0.3 g x d(-1) x 100
      g(-1) body mass, respectively) than for the 1.0-, 1.5-, and 2.0-G groups.
      Absolute values and rate of body mass gain were reduced with increases in
      gravity. CONCLUSION: Exposure to hypergravity attenuates body mass gain in a dose
      dependent manner, with a threshold possibly existing between 1.5- and 2.5-G for
      10-wk-old male rats.

PMID- 16909880
TI  - Vascular distribution of an ultrasound contrast agent used to simulate
      decompression bubbles.
AB  - OBJECTIVE: The objectives of this preliminary work were to evaluate the
      distribution of an ultrasound contrast agent (UCA) (microbubbles) in different
      arterial regions (brain, kidney, lower limbs) using the Doppler spectrum
      brightness analysis and to discuss the results in the context of decompression
      physiology. METHOD: There were four patients who instrumented with two pulsed
      Doppler sensors in order to monitor in real-time the spectrum of the middle
      cerebral femoral arteries. Renal arteries were investigated using an echo-Doppler
      probe handled by a sonographer. Measurements of the systolic mean, diastolic
      frequencies, qualitative, and quantitative analysis of the spectrum brightness
      intensity were performed before and after intravenous injection of a UCA.
      RESULTS: All of the systolic mean and diastolic arterial frequencies remained
      constant during the experiment. Some seconds after the first injection, the
      cerebral spectrum was heterogeneously enhanced with strong flashes over the
      entire spectrum. The renal and femoral spectrums were homogeneously reinforced.
      The spectrum brightness patterns did not change during the first 10 min.
      DISCUSSION: This work shows that the distribution of the UCA microbubbles within
      the vessel sections changed according to the distance from the heart, as
      suggested by the spectrum recorded at different sites. By mixing the blood, the
      heart could re-aggregate the UCA particles, even when they returned from the
      distal vascular regions where they were homogeneously distributed. The
      circulating microbubbles and their distribution within the arteries should be
      considered in decompression procedures with repetitive dives.

PMID- 16909881
TI  - Microgravity effects on fine motor skills: tying surgical knots during parabolic
      flight.
AB  - INTRODUCTION: The health provider on a space exploration mission cannot evacuate
      a patient to Earth. Contingency plans for medical intervention must be designed
      for autonomy. This study measured the effect of microgravity on performance of
      fine motor skills such as basic surgical tasks. METHODS: Eight subjects, six with
      medical and two with non-medical backgrounds, were evaluated during parabolic
      microgravity flights aboard NASA's KC-135. We evaluated their skill in tying
      surgical knots on simulated skin made of silicone using standard techniques for
      minimally invasive surgery. LabView software was developed to archive forces
      applied to the laparoscopic tool handles during knot-tying. Studies were
      controlled for medication (ScopeDex) and the aircraft environment. RESULTS: All
      participants completed the tests successfully. The data indicated that increased
      force was applied to the instruments and knot quality decreased during flight
      compared with ground control sessions. CONCLUSION: Specific metrics of surgical
      task performance are essential in developing education modules for providers of
      medical care during exploration-class missions.

PMID- 16909882
TI  - Mask-on hypoxia training for tactical jet aviators: evaluation of an alternate
      instructional paradigm.
AB  - INTRODUCTION: Hypoxia familiarization instruction has been an integral part of
      military aviation training for more than 60 yr. Traditionally, aircrew learn
      hypoxia recognition while being exposed to hypobaric conditions in a low-pressure
      chamber (LPC). A training device has been developed that induces hypoxia using
      mixed gas delivered through an aviator's oxygen mask. The reduced oxygen
      breathing device (ROBD) simulates the diminished oxygen present at altitude by
      mixing breathing air and nitrogen under normobaric conditions. The purpose of
      this paper is to describe an alternate hypoxia training paradigm that combines
      the ROBD with tactical flight simulators and to present results from student
      surveys. METHODS: Dynamic hypoxia instruction was provided inside F/A-18 tactical
      flight simulators using a second generation ROBD (ROBD-2). There were 121 naval
      aviators who were individually exposed to a simulated altitude of 7620 m (25,000
      ft) while performing complex flight duties. Subsequent to ROBD training, all
      students completed a 19-question, anonymous survey that asked them to rate the
      quality of the instruction. RESULTS: Of the 121 students trained with the ROBD-2
      in combination with a flight simulator, 114 (94.2%) were able to recognize their
      hypoxia symptoms and recover the aircraft, 117 (96.7%) rated ROBD training as
      more realistic, and 110 (90.9%) as more effective than traditional LPC training.
      DISCUSSION: Student feedback from this instructional evaluation indicates that
      using an ROBD in combination with actual flight duties is a safe, effective, and
      preferred means of training experienced tactical jet aviators to recognize and
      recover from hypoxia.

PMID- 16909883
TI  - Barodontalgia due to odontogenic inflammation in the jawbone.
AB  - A case is presented of severe anterior mandibular pain, which first appeared
      during descent of a long commercial flight, and lasted 3 d for a 28-yr-old
      military helicopter pilot. Apical periodontitis due to pulpal necrosis of the #31
      tooth was diagnosed as the causative pathology of the pain. This pain was not
      ever felt in his daily routine helicopter flights, up to 6000 ft, only in the
      pressurized chamber of a commercial flight to 7000-ft conditions. Although
      barodontalgia, dental pain evoked by barometric pressure change in an otherwise
      asymptomatic tooth, has relatively low prevalence nowadays, it seems that
      periodic dental vitality tests and panoramic imaging of the jaws are worthwhile
      for aircrew members.

PMID- 16909884
TI  - Robert Hooke, inventor of the vacuum pump and the first altitude chamber (1671).
AB  - Robert Hooke (1635-1703), an assistant researcher to Robert Boyle (1627-1691),
      invented the first functional British air pump. Applying it to scientific
      research, Hooke operated the world's first hypobaric chamber in 1671, using it
      for self-experimentation. He recorded the first physiological observations in an
      artificial altitude-equivalent environment up to 2400 m. Though Hooke's
      experiment showed some methodological insufficiencies, his imaginative
      experimental techniques were remarkable for their time and were indicative of the
      lively intellectual atmosphere of the Royal Society and the significant
      contributions of Hooke, who was a member. Two centuries passed before the French
      physiologist Paul Bert (1830-1886) conducted his famous laboratory-supported
      investigations of high altitude physiology. Bert played a decisive role in the
      discovery of the causes of decompression sickness; a contribution Hooke could not
      make due to the technical deficiencies of the 17th century.

PMID- 16909885
TI  - Traumatic subdural hematoma and medical certification.
AB  - Traumatic closed-head injury and subsequent subdural hematoma carries a high risk
      of post-traumatic seizure(s). This is particularly important to the airman, as
      sudden incapacitation due to seizure carries grave consequences if it occurs
      during aircraft operation.

PMID- 16909886
TI  - You're the flight surgeon: an unusual radiographic finding in a patient with back
      pain.

PMID- 16909887
TI  - Is there a doctor on board?

PMID- 16909888
TI  - Structure and function of protein modules in chromatin biology.
AB  - Chromatin-mediated gene transcription or silencing is a dynamic process in which
      binding of various proteins or protein complexes can displace nucleosomal
      histones from DNA to relieve repression or drive the gene into a highly
      repressed, silent state. Covalent modifications to DNA and histones associated
      with chromatin structural change play a crucial role in transcriptional
      regulation, with particular modifications on certain residues associated with a
      specific transcriptional outcome. In recent years a number of structural domains
      have been identified within chromatin-associated proteins, including DNA or RNA
      binding domains, protein-protein interaction domains and domains that recognize
      specific covalent modifications to histone tails. In this review we discuss the
      structural features of these protein modules and the functional roles they play
      in chromatin biology.

PMID- 16909889
TI  - The generation and recognition of histone methylation.
AB  - The posttranslational modification of histone proteins via methylation has
      important functions in gene activation, transcriptional silencing, establishment
      of chromatin states, and likely many aspects of DNA metabolism. The
      identification of numerous effector protein domains with the capability of
      binding methylated histones has significantly advanced our understanding of how
      such histone modifications may exert their biological effects. Here, we summarize
      aspects of the generation of arginine and lysine methylation marks on core
      histones, the characterization of the protein modules that interact with them,
      and how histone methylation cross-talks with other modifications.

PMID- 16909890
TI  - Histone ubiquitylation and the regulation of transcription.
AB  - The small (76 amino acids) and highly conserved ubiquitin protein plays key roles
      in the physiology of eukaryotic cells. Protein ubiquitylation has emerged as one
      of the most important intracellular signaling mechanisms, and in 2004 the Nobel
      Prize was awarded to Aaron Ciechanower, Avram Hersko, and Irwin Rose for their
      pioneering studies of the enzymology of ubiquitin attachment. One of the most
      common features of protein ubiquitylation is the attachment of polyubiquitin
      chains (four or more ubiquitin moieties attached to each other), which is a
      widely used mechanism to target proteins for degradation via the 26S proteosome.
      However, it is noteworthy that the first ubiquitylated protein to be identified
      was histone H2A, to which a single ubiquitin moiety is most commonly attached.
      Following this discovery, other histones (H2B, H3, H1, H2A.Z, macroH2A), as well
      as many nonhistone proteins, have been found to be monoubiquitylated. The role of
      monoubiquitylation is still elusive because a single ubiquitin moiety is not
      sufficient to target proteins for turnover, and has been hypothesized to control
      the assembly or disassembly of multiprotein complexes by providing a protein
      binding site. Indeed, a number of ubiquitin-binding domains have now been
      identified in both polyubiquitylated and monoubiquitylated proteins. Despite the
      early discovery of ubiquitylated histones, it has only been in the last five or
      so years that we have begun to understand how histone ubiquitylation is regulated
      and what roles it plays in the cell. This review will discuss current research on
      the factors that regulate the attachment and removal of ubiquitin from histones,
      describe the relationship of histone ubiquitylation to histone methylation, and
      focus on the roles of ubiquitylated histones in gene expression.

PMID- 16909891
TI  - Histone dynamics during transcription: exchange of H2A/H2B dimers and H3/H4
      tetramers during pol II elongation.
AB  - Chromatin within eukaryotic cell nuclei accommodates many complex activities that
      require at least partial disassembly and reassembly of nucleosomes. This
      disassembly/reassembly is thought to be somewhat localized when associated with
      processes such as site-specific DNA repair but likely occurs over extended
      regions during processive processes such as DNA replication or transcription.
      Here we review data addressing the effect of transcription elongation on
      nucleosome disassembly/reassembly, specifically focusing on the issue of
      transcription-dependent exchange of H2A/H2B dimers and H3/H4 tetramers. We
      suggest a model whereby passage of a polymerase through a nucleosome induces
      displacement of H2A/H2B dimers with a much higher probability than displacement
      of H3/H4 tetramers such that the extent of tetramer replacement is relatively low
      and proportional to polymerase density on any particular gene.

PMID- 16909892
TI  - The roles of chromatin remodelling factors in replication.
AB  - Dynamic changes of chromatin structure control DNA-dependent events, including
      DNA replication. Along with DNA, chromatin organization must be replicated to
      maintain genetic and epigenetic information through cell generations. Chromatin
      remodelling is important for several steps in replication: determination and
      activation of origins of replication, replication machinery progression,
      chromatin assembly and DNA repair. Histone chaperones such as the FACT complex
      assist DNA replication within chromatin, probably by facilitating both nucleosome
      disassembly and reassembly. ATP-dependent nucleosome remodelling enzymes of the
      SWI/SNF family, in particular imitation switch (ISWI)-containing complexes, have
      been linked to DNA and chromatin replication. They are targeted to replication
      sites to facilitate DNA replication and subsequent chromatin assembly.

PMID- 16909893
TI  - Chromatin modifications in DNA repair.
AB  - A requirement of nuclear processes that use DNA as a substrate is the
      manipulation of chromatin in which the DNA is packaged. Chromatin modifications
      cause alterations of histones and DNA, and result in a permissive chromatin
      environment for these nuclear processes. Recent advances in the fields of DNA
      repair and chromatin reveal that both histone modifications and chromatin
      remodeling complexes are essential for the repair of DNA lesions, such as DNA
      double strand breaks (DSBs). In particular, chromatin-modifying complexes, such
      as the INO80, SWR1, RSC, and SWI/SNF ATP-dependent chromatin-remodeling complexes
      and the NuA4 and Tip60 histone acetyltransferase complexes are implicated in DNA
      repair. The activity of these chromatin-modifying complexes influences the
      efficiency of the DNA repair process, which ultimately affects genome integrity
      and carcinogenesis. Thus, the process of DNA repair requires the cooperative
      activities of evolutionarily conserved chromatin-modifying complexes that
      facilitate the dynamic chromatin alterations needed during repair of DNA damage.

PMID- 16909894
TI  - Mechanisms for nucleosome movement by ATP-dependent chromatin remodeling
      complexes.
AB  - Chromatin remodeling complexes (remodelers) are a set of diverse multi-protein
      machines that reposition and restructure nucleosomes. Remodelers are specialized,
      containing unique proteins that assist in targeting, interaction with modified
      nucleosomes, and performing specific chromatin tasks. However, all remodelers
      contain an ATPase domain that is highly similar to known DNA
      translocases/helicases, suggesting that DNA translocation is a property common to
      all remodelers. Here we examine the different reactions they perform in vitro,
      focusing on the SWI/SNF and the ISWI complexes, and explore how DNA translocation
      might be utilized to execute various remodeling processes.

PMID- 16909896
TI  - Early steps in rotavirus cell entry.
AB  - Rotaviruses, the leading cause of severe dehydrating diarrhea in infants and
      young children worldwide, are non-enveloped viruses formed by three concentric
      layers of protein that enclose a genome of double-stranded RNA. These viruses
      have a specific cell tropism in vivo, infecting primarily the mature enterocytes
      of the villi of the small intestine. It has been found that rotavirus cell entry
      is a complex multistep process, in which different domains of the rotavirus
      surface proteins interact sequentially with different cell surface molecules,
      which act as attachment and entry receptors. These recently described molecules
      include integrins (alpha2beta1, alphavbeta3, and alphaxbeta2) and a heat shock
      protein (hsc70), and have been found to be associated with cell membrane lipid
      microdomains. The requirement for several cell molecules, which might need to be
      present and organized in a precise fashion, could explain the cell and tissue
      tropism of these viruses. This review focuses on recent data describing the
      interactions between the virus and its receptors, the role of lipid microdomains
      in rotavirus infection, and the possible mechanism of rotavirus cell entry.

PMID- 16909895
TI  - Attachment and cell entry of mammalian orthoreovirus.
AB  - Mammalian orthoreoviruses (reoviruses) serve as a tractable model system for
      studies of viral pathogenesis. Reoviruses infect virtually all mammals, but cause
      disease only in the very young. Prototype strains of the three reovirus serotypes
      differ in pathogenesis following infection of newborn mice. Reoviruses are
      nonenveloped, icosahedral particles that consist of ten segments of double
      stranded RNA encapsidated within two protein shells, the inner core and outer
      capsid. High-resolution structures of individual components of the reovirus outer
      capsid and a single viral receptor have been solved and provide insight into the
      functions of these molecules in viral attachment, entry, and pathogenesis.
      Attachment of reovirus to target cells is mediated by the reovirus sigma1
      protein, a filamentous trimer that projects from the outer capsid. Junctional
      adhesion molecule-A is a serotype-independent receptor for reovirus, and sialic
      acid is a coreceptor for serotype 3 strains. After binding to receptors on the
      cell surface, reovirus is internalized via receptor-mediated endocytosis.
      Internalization is followed by stepwise disassembly of the viral outer capsid in
      the endocytic compartment. Uncoating events, which require acidic pH and
      endocytic proteases, lead to removal of major outer-capsid protein sigma3,
      resulting in exposure of membrane-penetration mediator micro1 and a
      conformational change in attachment protein sigma1. After penetration of
      endosomes by uncoated particles, the transcriptionally active viral core is
      released into the cytoplasm, where replication proceeds. Despite major advances
      in defining reovirus attachment and entry mechanisms, many questions remain.
      Ongoing research is aimed at understanding serotype-dependent differences in
      reovirus tropism, viral cell-entry pathways, the individual and corporate roles
      of acidic pH and proteases in viral entry, and micro1 function in membrane
      penetration.

PMID- 16909897
TI  - Early steps in avian reovirus morphogenesis.
AB  - Avian reoviruses are important pathogens that may cause considerable economic
      losses in poultry farming. Their genome expresses at least eight structural and
      four nonstructural proteins, three of them encoded by the S1 gene. These viruses
      enter cells by receptor-mediated endocytosis, and acidification of virus
      containing endosomes is necessary for the virus to uncoat and release
      transcriptionally active cores into the cytosol. Avian reoviruses replicate
      within cytoplasmic inclusions of globular morphology, termed viral factories,
      which are not microtubule-associated, and which are formed by the nonstructural
      protein muNS. This protein also mediates the association of some viral proteins
      (but not of others) with inclusions, suggesting that the recruitment of viral
      proteins into avian reovirus factories has specificity. Avian reovirus
      morphogenesis is a complex and temporally controlled process that takes place
      exclusively within viral factories of infected cells. Core assembly takes place
      within the first 30 min after the synthesis of their protein components, and
      fully formed cores are then coated by outer-capsid polypeptides over the next 30
      min to generate mature infectious reovirions. Based on data from avian reovirus
      studies and on results reported for other members of the Reoviridae family, we
      present a model for avian reovirus gene expression and morphogenesis.

PMID- 16909898
TI  - Bluetongue virus assembly and morphogenesis.
AB  - Like other members of the Reoviridae, bluetongue virus faces the same constraints
      on structure and assembly that are imposed by a large dsRNA genome. However,
      since it is arthropod-transmitted, BTV must have assembly pathways that are
      sufficiently flexible to allow it to replicate in evolutionarily distant hosts.
      With this background, it is hardly surprising that BTV interacts with highly
      conserved cellular pathways during morphogenesis and trafficking. Indeed, recent
      studies have revealed striking parallels between the pathways involved in the
      entry and egress of nonenveloped BTV and those used by enveloped viruses. In
      addition, recent studies with the protein that is the major component of the BTV
      viroplasm have revealed how the assembly and, as importantly, the disassembly of
      this structure may be achieved. This is a first step towards resolving the
      interactions that occur in these virus 'assembly factories'. Overall, this review
      demonstrates that the integration of structural, biochemical and molecular data
      is necessary to fully understand the assembly and replication of this complex RNA
      virus.

PMID- 16909899
TI  - Reovirus structure and morphogenesis.
AB  - Assembly of a mature infectious virion from component parts is one of the last
      steps in the replicative cycle of most viruses. Recent advances in delineating
      aspects of this process for the mammalian orthoreoviruses (MRV), nonenveloped
      viruses composed of a genome of ten segments of double-stranded RNA enclosed in
      two concentric icosahedral protein capsids, are discussed. Analyses of
      temperature-sensitive (ts) assembly-defective reovirus mutants have been used to
      better understand requirements for viral inclusion formation and capsid
      morphogenesis. Newly determined high-resolution structures of virtually all MRV
      proteins, combined with complete MRV genomic sequence information and elucidation
      of sequence lesions in ts mutants, is now providing a context for molecularly
      understanding interactions that promote, or abrogate, reovirus capsid assembly.
      Additional advances in understanding required signals for whole genome
      construction from sets of the ten individual genes, and in transcapsidation of
      subviral particles with engineered outer capsid proteins, provide additional
      molecular genetic understanding of reovirus protein structure-function and
      morphogenesis.

PMID- 16909900
TI  - Rotavirus genome replication and morphogenesis: role of the viroplasm.
AB  - The rotaviruses, members of the family Reoviridae, are icosahedral triple-layered
      viruses with genomes consisting of 11 segments of double-stranded (ds)RNA. A
      characteristic feature of rotavirus-infected cells is the formation of large
      cytoplasmic inclusion bodies, termed viroplasms. These dynamic and highly
      organized structures serve as viral factories that direct the packaging and
      replication of the viral genome into early capsid assembly intermediates.
      Migration of the intermediates to the endoplasmic reticulum (ER) initiates a
      budding process that culminates in final capsid assembly. Recent information on
      the development and organization of viroplasms, the structure and function of its
      components, and interactive pathways linking RNA synthesis and capsid assembly
      provide new insight into how these microenvironments serve to interface the
      replication and morphogenetic processes of the virus.

PMID- 16909901
TI  - Structural studies on orbivirus proteins and particles.
AB  - X-ray and electron microscopy analysis of Bluetongue virus (BTV), the type
      species of the Orbivirus genus within the family Reoviridae, have revealed
      various aspects of the organisation and structure of the proteins that form the
      viral capsid. Orbiviruses have a segmented dsRNA genome, which imposes
      constraints on their structure and life cycle. The atomic structure of the BTV
      core particle, the key viral component which transcribes the viral mRNA within
      the cell cytoplasm, revealed the architecture and assembly of the major core
      proteins VP7 and VP3. In addition, these studies formed the basis for a plausible
      model for the organisation of the dsRNA viral genome and the arrangement of the
      viral transcriptase complex (composed of the RNA-dependent RNA polymerase, the
      viral capping enzyme and RNA helicase) that resides within the core particle.
      Electron cryo-microscopy of the viral particle has shown how the two viral
      proteins VP2 and VP5 are arranged to form the outer capsid, with distinct packing
      arrangements between them and the core protein VP7. By comparison of the outer
      capsid proteins of orbiviruses with those of other nonturreted members of the
      family Reoviridae, we are able to propose a more detailed model of these
      structures and possible mechanisms for cell entry. Further structural results are
      also discussed including the atomic structure of an N-terminal domain of
      nonstructural protein NS2, a protein involved in virus genome assembly and
      morphogenesis.

PMID- 16909902
TI  - Rotavirus assembly: an alternative model that utilizes an atypical trafficking
      pathway.
AB  - We review here recent advances in our knowledge on trafficking and assembly of
      rotavirus and rotaviral proteins in intestinal cells. Assembly of rotavirus has
      been extensively studied in nonpolarized kidney epithelial MA104 cells, where
      several data indicate that most if not all the steps of rotavirus assembly take
      place within the endoplasmic reticulum (ER) and that rotavirus is release upon
      cell lysis. We focus here on data obtained in intestinal cells that argue for
      another scheme of rotavirus assembly, where the final steps seem to take place
      outside the ER with an apically polarized release of rotavirus without
      significant cell lysis. One of the key observations made by different groups is
      that VP4 and other structural proteins interact substantially with specialized
      membrane microdomains enriched in cholesterol and sphingolipids termed rafts. In
      addition, recent data point to the fact that VP4 does not localize within the ER
      or the Golgi apparatus in infected intestinal cells. The mechanisms by which VP4,
      a cytosolic protein, may be targeted to the apical membrane in these cells and
      assembles with the other structural proteins are discussed. The identification of
      cellular proteins such as Hsp70, flotillin, rab5, PRA1 and cytoskeletal
      components that interact with VP4 may help to define an atypical polarized
      trafficking pathway to the apical membrane of intestinal cells that will be raft
      dependent and by-pass the classical exocytic route.

PMID- 16909903
TI  - The regulation of chromatin and DNA-methylation patterns in blood cell
      development.
AB  - All developmental processes in metazoans require the establishment of different
      genetic programs to generate functionally specialised cells. Differential gene
      expression is also the basis for the alterations in the developmental potential
      of differentiating cells. However, the molecular details concerning how this is
      achieved are still poorly understood. The haematopoietic system has for many
      years served as an excellent model system to studyhow developmental processes are
      regulated at the epigenetic level. In this article we will summarise recent
      results from others and from our own laboratory that have yielded profound
      insights into the general principles of how cell-fate decisions are regulated in
      the cell nucleus. We summarise (1) how the interplay of sequence-specific
      transcription factors and chromatin components is responsible for the cell type
      and cell stage-specific activation of specific genes and (2) how these findings
      impact on current concepts of epigenetic regulation of developmental processes.

PMID- 16909904
TI  - Methylation dynamics in the early mammalian embryo: implications of genome
      reprogramming defects for development.
AB  - In mouse and most other mammalian species, the paternal and maternal genomes
      undergo parent-specific epigenetic reprogramming during preimplantation
      development. The paternal genome is actively demethylated within a few hours
      after fertilization in the mouse, rat, pig, bovine, and human zygote, whereas the
      maternal genome is passively demethylated by a replication-dependent mechanism
      after the two-cell embryo stage. These genome-wide demethylation waves may have a
      role in reprogramming of the genetically inactive sperm and egg chromatin for
      somatic development. Disturbances in this highly coordinated process may
      contribute to developmental failures and defects in mammals. The frequency and
      severity of abnormal phenotypes increase after interfering with or bypassing
      essential steps of gametogenesis, early embryogenesis, or both. Nevertheless, it
      is plausible that normal fertilization, assisted reproduction, and embryo cloning
      are all susceptible to similar dysregulation of epigenetic components. Although
      the mouse maybe an excellent model for early human development, species and
      strain differences in the molecular and cellular events shortly after
      fertilization may have important implications for the efficiency of epigenetic
      reprogramming and the incidence of reprogramming defects. Some species, i.e.,
      rabbit and sheep, do not require drastic genome-wide demethylation for early
      development, most likely because the transition from maternal to embryonic
      control occurs relatively late during preimplantation development. A better
      understanding of key reprogramming factors--in particular the demethylase
      activity in the fertilized egg--is crucial for improving human infertility
      treatment and the efficiency of mammalian embryo cloning.

PMID- 16909905
TI  - Epigenetic regulation in Drosophila.
AB  - Epigenetic regulation of gene transcription relies on molecular marks like DNA
      methylation or histone modifications. Here we review recent advances in our
      understanding of epigenetic regulation in the fruit fly Drosophila melanogaster.
      In the past, DNA methylation research has primarily utilized mammalian model
      systems. However, several recent landmark discoveries have been made in other
      organisms. For example, the interaction between DNA methylation and histone
      methylation was first described in the filamentous fungus Neurospora crassa.
      Another example is provided by the interaction between epigenetic modifications
      and the RNA interference (RNAi) machinery that was first reported in the fission
      yeast Schizosaccharomyces pombe. Another organism with great experimental power
      is the fruit fly Drosophila. Epigenetic regulation by chromatin has been
      extensively analyzed in the fly and several of the key components have been
      discovered in this organism. In this chapter, we will focus on three aspects that
      represent the complexity of epigenetic gene regulation. (1) We will discuss the
      available data about the DNA methylation system, (2) we will illuminate the
      interaction between DNA methylation and chromatin regulation, and (3) we will
      provide an overview over the Polycomb system of epigenetic chromatin modifiers
      that has proved to be an important paradigm for a chromatin system regulating
      epigenetic programming.

PMID- 16909906
TI  - Epimutations in human disease.
AB  - Epigenetics is the study of genes during development. Gene expression states are
      set by transcriptional activators and repressors and locked in by cell-heritable
      chromatin states. Inappropriate expression or repression of genes can change
      developmental trajectories and result in disease. Aberrant chromatin states
      leading to aberrant gene expression patterns (epimutations) have been detected in
      several recognizable syndromes as well as in cancer. They can occur secondary to
      a DNA mutation in a cis- or trans-acting factor, or as a "true" or primary
      epimutation in the absence of any DNA sequence change. Primary epimutations often
      occur after fertilization and lead to somatic mosaicism. It has been estimated
      that the rate of primary epimutations is one or two orders of magnitude greater
      than somatic DNA mutation. Therefore, the contribution of epimutations to human
      disease is probably underestimated.

PMID- 16909907
TI  - Epigenotypes of latent herpesvirus genomes.
AB  - Epigenotypes are modified cellular or viral genotypes which differ in
      transcriptional activity in spite of having an identical (or nearly identical)
      DNA sequence. Restricted expression of latent, episomal herpesvirus genomes is
      also due to epigenetic modifications. There is no virus production (lytic viral
      replication, associated with the expression of all viral genes) in tight latency.
      In vitro experiments demonstrated that DNA methylation could influence the
      activity of latent (and/or crucial lytic) promoters of prototype strains
      belonging to the three herpesvirus subfamilies (alpha-, beta-, and gamma
      herpesviruses). In vivo, however, DNA methylation is not a major regulator of
      herpes simplex virus type 1 (HSV-1, a human alpha-herpesvirus) latent gene
      expression in neurons of infected mice. In these cells, the promoter/enhancer
      region of latency-associated transcripts (LATs) is enriched with acetyl histone
      H3, suggesting that histone modifications may control HSV-1 latency in terminally
      differentiated, quiescent neurons. Epstein-Barr virus (EBV, a human gamma
      herpesvirus) is associated with a series of neoplasms. Latent, episomal EBV
      genomes are subject to host cell-dependent epigenetic modifications (DNA
      methylation, binding of proteins and protein complexes, histone modifications).
      The distinct viral epigenotypes are associated with distinct EBV latency types,
      i.e., cell type-specific usage of latent EBV promoters controlling the expression
      of latent, growth transformation-associated EBV genes. The contribution of major
      epigenetic mechanisms to the regulation of latent EBV promoters is variable. DNA
      methylation contributes to silencing of Wp and Cp (alternative promoters for
      transcripts coding for the nuclear antigens EBNA 1-6) and LMP1p, LMP2Ap, and
      LMP2Bp (promoters for transcripts encoding transmembrane proteins). DNA
      methylation does not control, however, Qp (a promoter for EBNA1 transcripts only)
      in lymphoblastoid cell lines (LCLs), although in vitro methylated Qp-reporter
      gene constructs are silenced. The invariably unmethylated Qp is probably switched
      off by binding of a repressor protein in LCLs.

PMID- 16909908
TI  - Epigenetics of complex diseases: from general theory to laboratory experiments.
AB  - Despite significant effort, understanding the causes and mechanisms of complex
      non-Mendelian diseases remains a key challenge. Although numerous molecular
      genetic linkage and association studies have been conducted in order to explain
      the heritable predisposition to complex diseases, the resulting data are quite
      often inconsistent and even controversial. In a similar way, identification of
      environmental factors causal to a disease is difficult. In this article, a new
      interpretation of the paradigm of "genes plus environment" is presented in which
      the emphasis is shifted to epigenetic misregulation as a major etiopathogenic
      factor. Epigenetic mechanisms are consistent with various non-Mendelian
      irregularities of complex diseases, such as the existence of clinically
      indistinguishable sporadic and familial cases, sexual dimorphism, relatively late
      age of onset and peaks of susceptibility to some diseases, discordance of
      monozygotic twins and major fluctuations on the course of disease severity. It is
      also suggested that a substantial portion of phenotypic variance that
      traditionally has been attributed to environmental effects may result from
      stochastic epigenetic events in the cell. It is argued that epigenetic
      strategies, when applied in parallel with the traditional genetic ones, may
      significantly advance the discovery of etiopathogenic mechanisms of complex
      diseases. The second part of this chapter is dedicated to a review of laboratory
      methods for DNA methylation analysis, which may be useful in the study of complex
      diseases. In this context, epigenetic microarray technologies are emphasized, as
      it is evident that such technologies will significantly advance epigenetic
      analyses in complex diseases.

PMID- 16909909
TI  - MSL proteins and the regulation of gene expression.
AB  - Epigenetics describes changes in genome function that occur without a change in
      the DNA sequence. Dosage compensation is a prime example of the regulation of
      gene expression by an epigenetic mechanism. Dosage compensation has evolved to
      balance the expression of sex-linked genes in males and females, which possess
      different numbers of sex chromosomes. However, the genetic sequence of the
      chromosomes is the same in both sexes. This mechanism therefore needs (1) to
      function in a sex-specific manner, (2) to target the sex chromosome from amongst
      the autosomes and (3) to establish and maintain through development a precise,
      equalised level of gene expression in one sex compared to the other. The process
      by which dosage compensation is orchestrated has been well characterised in fruit
      flies and mammals. Although each has evolved a specific dosage-compensation
      mechanism, these systems share some underlying themes; the molecular components
      that mediate dosage compensation in both include non-coding RNA molecules, which
      act as nucleation points for the compensation process. Both systems utilise
      chromatin-modifying enzymes to remodel large domains of a chromosome. This review
      will discuss the mechanism of dosage compensation in Drosophila in light of
      recent developments that have brought into question the previous model of dosage
      compensation.

PMID- 16909910
TI  - DNA methylation profiles of female steroid hormone-driven human malignancies.
AB  - Tumor DNA contains valuable clues about the origin and pathogenesis of human
      cancers. Alterations in DNA methylation can lead to silencing of genes associated
      with distinct tumorigenic pathways. These pathway-specific DNA methylation
      changes help define tumor-specific DNA methylation profiles that can be used to
      further our understanding of tumor development, as well as provide tools for
      molecular diagnosis and early detection of cancer. Female sex hormones have been
      implicated in the etiology of several of the women's cancers including breast,
      endometrial, ovarian, and proximal colon cancers. We have reviewed the DNA
      methylation profiles of these cancers to determine whether the hormonal
      regulation of these cancers results in specific DNA methylation alterations.
      Although subsets of tumors in each of these four types of cancers were found to
      share some DNA methylation alterations, we did not find evidence for global
      hormone-specific DNA methylation alterations, suggesting that female sex hormones
      may participate in different tumorigenic pathways that are associated with
      distinct DNA methylation-based molecular signatures. One such pathway may include
      MLH1 methylation in the context of the CpG island methylator phenotype.

PMID- 16909911
TI  - Genome-wide analysis of DNA methylation changes in human malignancies.
AB  - DNA methylation is an epigenetic modification of the DNA sequence and thus does
      not change the genetic code but affects chromosomal stability and gene
      expression. DNA methylation patterns are heritable and can be passed on to the
      daughter cell. In this review, we briefly summarize our current knowledge on
      normal DNA methylation patterns and move on to discuss the current state of the
      field with respect to altered DNA methylation in cancer. We make a special
      attempt to address current questions relating to genome-wide DNA methylation
      patterns. Since DNA methylation is used as a therapeutic target in clinical
      studies, it is of utmost importance to define potential target sequences that
      could be used as diagnostic or prognostic markers. We conclude the review by
      outlining possible scenarios that may explain tumor type-specific DNA methylation
      patterns described by assays evaluating genome-wide levels of DNA methylation.

PMID- 16909912
TI  - Decreased fidelity in replicating DNA methylation patterns in cancer cells leads
      to dense methylation of a CpG island.
AB  - Cancer cells that have a large number of aberrantly methylated CpG islands (CGIs)
      are known to have CpG island methylator phenotype (CIMP), and decreased fidelity
      in replicating methylation patters has been analyzed as an underlying mechanism.
      First we developed a method to analyze the number of errors in replicating CpG
      methylation patterns in a defined period. A single cell was expanded into 106
      cells, and the number of errors during the culture was measured by counting the
      deviation from the original methylation patterns. It was shown that methylated
      status of a CpG site was more stably inherited than unmethylated status,
      suggesting that the genome is constantly exposed to de novo methylation. Promoter
      CGIs showed higher fidelities than CGIs outside promoter regions. We then
      analyzed error rates in two gastric cancer cell lines without CIMP and two with
      CIMP for five promoter CGIs. Two CIMP(-) cell lines showed error rates smaller
      than 1.0x10(-3) errors per site per generation (99.90%-100% fidelity) for all the
      five CGIs. In contrast, AGS cells showed significantly elevated error rates,
      mainly due to increased de novo methylation, in three CGIs (1.6- to 3.2-fold),
      and KATOIII cells showed a significantly elevated error rate in one CGI (2.2
      fold). Presence of densely methylated DNA molecules was observed only in KATOIII
      and AGS. These data demonstrated that some cancer cells have decreased fidelity
      in replicating CpG methylation patterns that underlie CIMP.

PMID- 16909913
TI  - Methylation of endogenous human retroelements in health and disease.
AB  - Retroelements constitute approximately 45% of the human genome. Long interspersed
      nuclear element (LINE) autonomous retrotransposons are predominantly represented
      by LINE-1, nonautonomous small interspersed nuclear elements (SINEs) are
      primarily represented by ALUs, and LTR retrotransposons by several families of
      human endogenous retroviruses (HERVs). The vast majority of LINE and HERV
      elements are densely methylated in normal somatic cells and contained in inactive
      chromatin. Methylation and chromatin structure together ensure a stable
      equilibrium between retroelements and their host. Hypomethylation and expression
      in developing germ cells opens a "window of opportunity" for retrotransposition
      and recombination that contribute to human evolution, but also inherited disease.
      In somatic cells, the presence of retroelements may be exploited to organize the
      genome into active and inactive regions, to separate domains and functional
      regions within one chromatin domain, to suppress transcriptional noise, and to
      regulate transcript stability. Retroelements, particularly ALUs, may also fulfill
      physiological roles during responses to stress and infections. Reactivation and
      hypomethylation of LINEs and HERVs may be important in the pathophysiology of
      cancer and various autoimmune diseases, contributing to chromosomal instability
      and chronically aberrant immune responses. The emerging insights into the
      pathophysiological importance of endogenous retroelements accentuate the gaps in
      our knowledge of how these elements are controlled in normal developing and
      mature cells.

PMID- 16909914
TI  - Cancer-linked DNA hypomethylation and its relationship to hypermethylation.
AB  - It is not surprising that cancer, a kind of derangement of development, hijacks
      DNA methylation, which is necessary for normal mammalian embryogenesis. Both
      decreases and increases in DNA methylation are a frequent characteristic of a
      wide variety of cancers. There is often more hypomethylation than
      hypermethylation of DNA during carcinogenesis, leading to a net decrease in the
      genomic 5-methylcytosine content. Although the exact methylation changes between
      different cancers of the same type are not the same, there are cancer type
      specific differences in the frequency of hypermethylation or hypomethylation of
      certain genomic sequences. These opposite types of DNA methylation changes appear
      to be mostly independent of one another, although they may arise because of a
      similar abnormality leading to long-lasting epigenetic instability in cancers.
      Both tandem and interspersed DNA repeats often exhibit cancer-associated
      hypomethylation. However, one of these repeated sequences (NBL2) displayed
      predominant increases in methylation in some ovarian carcinomas and Wilms tumors
      and decreases in others. Furthermore, decreases and increases in CpG methylation
      can be interspersed within a small subregion of the 1.4-kb repeat unit of these
      tandem arrays. While the transcription-silencing role of DNA hypermethylation at
      promoters of many tumor-suppressor genes is clear, the biological effects of
      cancer-linked hypomethylation of genomic DNA are less well understood. Evidence
      suggests that DNA hypomethylation functions in direct or indirect control of
      transcription and in destabilizing chromosomal integrity. Recent studies of
      cancer-linked DNA hypomethylation indicate that changes to DNA methylation during
      tumorigenesis and tumor progression have a previously underestimated plasticity
      and dynamic nature.

PMID- 16909915
TI  - Structure of enteric neurons.
AB  - The ENS contains numerous different neuron populations which belong to three main
      groups, primary afferent neurons, interneurons and effector neurons. The most
      extensive knowledge on the different enteric neuron types is derived from studies
      in the guinea pig. A significant obstacle for the transfer of this knowledge to
      putative equivalent enteric neurons of other species, including human, is species
      differences as to their morphological, chemical, physiological etc. phenotypes.
      Modern morphological classifications are based on the work of the Russian
      histologist Dogiel. Since the late 1970s, refined morphological classifications
      of enteric neurons beyond Dogiel have been attempted mainly in two species, the
      pig and the guinea pig. These reflect the immunohistochemical diversity of
      enteric neurons more precisely but are far from being complete. In this paper, we
      follow two aims. First, we have presented an overview on the chemical coding of
      the morphological neuron types described by Stach in the pig intestine. In doing
      so, we have pointed out the difference between the definitions of type I neurons
      given by Dogiel and Stach. Second, we have attempted to provide a basis for the
      morpho-chemical classification of human enteric neurons as revealed by their
      immunoreactivity for NFs and several neuroactive substances or related markers.
      According to results from guinea pig, where there is functional evidence, human
      morphological type II neurons (non-dendritic, multiaxonal; co-reactive for NF,
      CAR, SOM, SP) seem to be the intrinsic primary afferent neurons. This conclusion
      is based primarily on structural equivalence. Human ENK-positive, stubby (type I)
      neurons maybe ascending interor motorneurons. In contrast, nitrergic, VIP
      reactive spiny (type I) neurons maybe descending inter- or motor neurons.
      Further, morphologically defined human neuron types, i.e. type III, type V and
      dendritic type II neurons, are non-nitrergic but could not be chemically defined
      as yet. Future investigations of morpho-chemical characteristics of human enteric
      neurons including also other cytoskeletal markers will provide a broader basis
      for neurohistopathological diagnostics of gut diseases.

PMID- 16909916
TI  - Paneth cell alpha-defensin synthesis and function.
AB  - Endogenous antimicrobial peptides (AMPs) mediate innate immunity in every species
      in which they have been investigated. Cathelicidins and defensins are the two
      major AMP families in mammals, and they are abundant components of phagocytic
      leukocytes and are released by epithelial cells at mucosal surfaces. In the small
      intestine, Paneth cells at the base of the crypts of Lieberkuhn secrete alpha
      defensins and additional AMPs at high levels in response to cholinergic
      stimulation and when exposed to bacterial antigens. Paneth cell alpha-defensins
      evolved to function in the extracellular environment with broad-spectrum
      antimicrobial activities, and they constitute the majority of bactericidal
      peptide activity secreted by Paneth cells. The release of Paneth cell products
      into the crypt lumen is inferred to protect mitotically active crypt cells from
      colonization by potential pathogens and confers protection from enteric
      infection, as is evident from the immunity of mice expressing a human Paneth cell
      alpha-defensin transgene to oral infection by Salmonella enterica serovar
      Typhimurium. alpha-Defensins in Paneth cell secretions also may interact with
      bacteria in the intestinal lumen above the crypt-villus boundary and influence
      the composition of the enteric microbial flora. Mutations that cause defects in
      the activation, secretion, dissolution, and bactericidal effects of Paneth cell
      AMPs may alter crypt innate immunity and contribute to immunopathology.

PMID- 16909917
TI  - Immunomodulatory properties of defensins and cathelicidins.
AB  - Host defence peptides are a conserved component of the innate immune response in
      all complex life forms. In humans, the major classes of host defence peptides
      include the alpha- and beta-defensins and the cathelicidin, hCAP-18/LL-37. These
      peptides are expressed in the granules of neutrophils and by a wide variety of
      tissue types. They have many roles in the immune response including both indirect
      and direct antimicrobial activity, the ability to act as chemokines as well as
      induce chemokine production leading to recruitment of leukocytes to the site of
      infection, the promotion of wound healing and an ability to modulate adaptive
      immunity. It appears that many of these properties are mediated though direct
      interaction of peptides with the cells of the innate immune response including
      monocytes, dendritic cells, T cells and epithelial cells. The importance of these
      peptides in immune responses has been demonstrated since animals defective in the
      expression of certain host defence peptides show greater susceptibility to
      bacterial infections. In the very few instances in which human patients have been
      demonstrated to have defective host defence peptide expression, these individuals
      suffer from frequent infections. Although studies of the immunomodulatory
      properties of these peptides are in their infancy, there is a growing body of
      evidence suggesting that the immunomodulatory properties of these small,
      naturally occurring molecules might be harnessed for development as novel
      therapeutic agents.

PMID- 16909918
TI  - Host antimicrobial defence peptides in human disease.
AB  - Antimicrobial peptides or host defence peptides are endogenous peptide
      antibiotics, which have been confirmed as an essential part of the immune system.
      Apart from direct killing of bacteria, a role for the peptides in antiviral and
      immunomodulatory functions has recently been claimed. In this chapter we have
      focused on the host contact with microbes, where these host defence peptides are
      key players. The interplay with commensals and pathogens in relation to
      antimicrobial peptide expression is discussed, with specific emphasis on the
      respiratory and the alimentary systems. A possible novel difference in epithelial
      interactions between commensals and pathogens is considered in relation to
      disease.

PMID- 16909919
TI  - Antimicrobial peptides: an essential component of the skin defensive barrier.
AB  - The skin is positioned at the interface between an organism's internal milieu and
      an external environment characterized by constant assault with potential
      microbial pathogens. While the skin was formerly considered an inactive physical
      protective barrier that participates in host immune defense merely by blocking
      entry of microbial pathogens, it is now apparent that a major role of the skin is
      to defend the body by rapidly mounting an innate immune response to injury and
      microbial insult. In the skin, both resident and infiltrating cells synthesize
      and secrete small peptides that demonstrate broad-spectrum antimicrobial activity
      against bacteria, fungi, and enveloped viruses. Antimicrobial peptides also act
      as multifunctional immune effectors by stimulating cytokine and chemokine
      production, angiogenesis, and wound healing. Cathelicidins and defensins comprise
      two major families of skin-derived antimicrobial peptides, although numerous
      others have been described. Many such immune defense molecules are currently
      being developed therapeutically in an attempt to combat growing bacterial
      resistance to conventional antibiotics.

PMID- 16909920
TI  - Antimicrobial peptides versus invasive infections.
AB  - It has been estimated that there are more microorganisms within and upon the
      human body than there are human cells. By necessity, every accessible niche must
      be defended by innate mechanisms to prevent invasive infection, and ideally that
      precludes the need for robust inflammatory responses. Yet the potential for
      pathogens to transcend the integument actively or passively and access the
      bloodstream emphasizes the need for rapid and potent antimicrobial defense
      mechanisms within the vascular compartment. Antimicrobial peptides from
      leukocytes have long been contemplated as being integral to defense against these
      infections. Recently, platelets are increasingly recognized for their likely
      multiple roles in antimicrobial host defense. Platelets and leukocytes share many
      structural and functional archetypes. Once activated, both cell types respond in
      specific ways that emphasize key roles for their antimicrobial peptides in host
      defense efficacy: (a) targeted accumulation at sites of tissue injury or
      infection; (b) direct interaction with pathogens; and (c) deployment of
      intracellular (leukocyte phagosomes) or extracellular (platelet secretion)
      antimicrobial peptides. Antimicrobial peptides from these cells exert rapid,
      potent, and direct antimicrobial effects against organisms that commonly access
      the bloodstream. Experimental models in vitro and in vivo show that antimicrobial
      peptides from these cells significantly contribute to prevent or limit infection.
      Moreover, certain platelet antimicrobial proteins are multifunctional kinocidins
      (microbicidal chemokines) that recruit leukocytes to sites of infection, and
      potentiate the antimicrobial mechanisms of these cells. In turn, pathogens pre
      decorated by kinocidins may be more efficiently phagocytosed and killed by
      leukocytes and their antimicrobial peptide arsenal. Hence, multiple and relevant
      interactions between platelets and leukocytes have immunologic functions yet to
      be fully understood. A clearer definition of these interactions, and the
      antimicrobial peptide effectors contributing to these functions, will
      significantly advance our understanding of antimicrobial host defense against
      invasive infection. In addition, this knowledge may accelerate development of
      novel anti-infective agents and strategies against pathogens that have become
      refractory to conventional antimicrobials.

PMID- 16909921
TI  - Antimicrobial peptides in the airway.
AB  - The airway provides numerous defense mechanisms to prevent microbial colonization
      by the large numbers of bacteria and viruses present in ambient air. An important
      component of this defense is the antimicrobial peptides and proteins present in
      the airway surface fluid (ASF), the mucin-rich fluid covering the respiratory
      epithelium. These include larger proteins such as lysozyme and lactoferrin, as
      well as the cationic defensin and cathelicidin peptides. While some of these
      peptides, such as human beta-defensin (hBD)-1, are present constitutively,
      others, including hBD2 and -3 are inducible in response to bacterial recognition
      by Toll-like receptor-mediated pathways. These peptides can act as microbicides
      in the ASF, but also exhibit other activities, including potent chemotactic
      activity for cells of the innate and adaptive immune systems, suggesting they
      play a complex role in the host defense of the airway. Inhibition of
      antimicrobial peptide activity or gene expression can result in increased
      susceptibility to infections. This has been observed with cystic fibrosis (CF),
      where the CF phenotype leads to reduced antimicrobial capacity of peptides in the
      airway. Pathogenic virulence factors can inhibit defensin gene expression, as can
      environmental factors such as air pollution. Such an interference can result in
      infections by airway-specific pathogens including Bordetella bronchiseptica,
      Mycobacterium tuberculosis, and influenza virus. Research into the modulation of
      peptide gene expression in animal models, as well as the optimization of peptide
      based therapeutics shows promise for the treatment and prevention of airway
      infectious diseases.

PMID- 16909922
TI  - Hepcidin--a peptide hormone at the interface of innate immunity and iron
      metabolism.
AB  - Hepcidin is a cationic amphipathic peptide made in the liver, released into
      plasma and excreted in urine. Hepcidin is the homeostatic regulator of intestinal
      iron absorption, iron recycling by macrophages, and iron mobilization from
      hepatic stores, but it is also markedly induced during infections and
      inflammation. Under the influence of hepcidin, macrophages, hepatocytes, and
      enterocytes retain iron that would otherwise be released into plasma. Hepcidin
      acts by inhibiting the efflux of iron through ferroportin, the sole known iron
      exporter that is expressed in the small intestine, and in hepatocytes and
      macrophages. As befits an iron-regulatory hormone, hepcidin synthesis is
      increased by iron loading, and decreased by anemia and hypoxia. Hepcidin is also
      rapidly induced by cytokines, including IL-6. The resulting decrease in plasma
      iron levels eventually limits iron availability to erythropoiesis and contributes
      to the anemia associated with infection and inflammation. The decrease in
      extracellular iron concentrations due to hepcidin probably limits iron
      availability to invading microorganisms, thus contributing to host defense.

PMID- 16909923
TI  - Innate host defense of human vaginal and cervical mucosae.
AB  - Host defense responses of the human female genital tract mucosa to pathogenic
      microbes and viruses are mediated in part by the release of antimicrobial
      substances into the overlying mucosal fluid. While host defense has long been
      considered a prominent function of vaginal and cervical mucosae, evidence that
      cationic antimicrobial peptides and proteins have fundamental roles in the innate
      host defense of this tissue has only recently become available. This chapter
      explores elements of the physical and chemical defense barriers of the
      cervicovaginal mucosa, which protect against infections of the lower genital
      tract. Cationic antimicrobial and antiviral polypeptide components of
      cervicovaginal fluid are discussed in detail, with special emphasis placed on the
      defensin family of peptides as well as polypeptides that are active against
      viruses such as HIV-1. The reader should be cognizant that each polypeptide by
      itself does not provide complete protection of the genital tract. On the
      contrary, the abundance and multiplicity of antimicrobial peptides and proteins
      suggest protection of the cervicovaginal mucosa may be best realized from the
      aggregate effector molecules.

PMID- 16909924
TI  - Molecular mechanisms of bacterial resistance to antimicrobial peptides.
AB  - Cationic antimicrobial peptides (CAMPs) are integral compounds of the
      antimicrobial arsenals in virtually all kinds of organisms, with important roles
      in microbial ecology and higher organisms' host defense. Many bacteria have
      developed countermeasures to limit the efficacy of CAMPs such as defensins,
      cathelicidins, kinocidins, or bacteriocins. The best-studied bacterial CAMP
      resistance mechanisms involve electrostatic repulsion of CAMPs by modification of
      cell envelope molecules, proteolytic cleavage of CAMPs, production of CAMP
      trapping proteins, or extrusion of CAMPs by energy-dependent efflux pumps. The
      repertoire of CAMPs produced by a given host organism and the efficiency of
      microbial CAMP resistance mechanisms appear to be crucial in host-pathogen
      interactions, governing the composition of commensal microbial communities and
      the virulence of bacterial pathogens. However, all CAMP resistance mechanisms
      have limitations and bacteria have never succeeded in becoming fully insensitive
      to a broad range of CAMPs. CAMPs or conserved CAMP resistance factors are
      discussed as new mediators and targets, respectively, of novel and sustainable
      anti-infective strategies.

PMID- 16909925
TI  - Bacterial evasion of antimicrobial peptides by biofilm formation.
AB  - Biofilm formation is a main virulence determinant in many bacterial infections.
      It significantly increases bacterial resistance to antibiotics and innate host
      defense. In general, the specific physiology of biofilms and the barrier function
      of the extracellular biofilm matrix determine resistance to antibacterials.
      However, resistance to antimicrobial peptides appears to be mainly based on the
      interaction with biofilm and capsule exopolymers. These polymers may work by
      electrostatic repulsion and/or sequestration of antibacterial substances. As
      biofilm polymers play an eminent role in biofilm structuring and resistance,
      their destruction by dedicated enzymes is a promising attempt to prevent
      colonization and develop treatment for biofilm-associated infections.

PMID- 16909926
TI  - Decreased cardiac sarcoplasmic reticulum Ca2+ -ATPase activity contributes to
      cardiac dysfunction in streptozotocin-induced diabetic rats.
AB  - Diabetic cardiomyopathy is characterized by reduced cardiac contractility due to
      direct changes in myocardium function independent of vascular disease. This study
      is to investigate the alterations of cardiac sarcoplasmic reticulum Ca2+ -ATPase
      activity and cardiac function in streptozotocin-induced diabetic rats. Diabetes
      mellitus (DM) was induced in male Wistar rats by intraperitoneal injection of
      streptozotocin. The activity of myocardium sarcoplasmic reticulum Ca2+ -ATPase
      and the left ventricular hemodynamic parameters were measured in DM rats 4 weeks,
      6 weeks and 8 weeks after streptozotocin was administered. Phospholamban mRNA
      expression was detected by reverse transcription-polymerase chain reaction, and
      the protein levels of phospholamban and sarcoplasmic reticulum Ca2+ -ATPase were
      determined by Western blot. Normal rats served as control group. It was found
      that in DM rats 4 weeks after streptozotocin injection, the cardiac function,
      myocardium sarcoplasmic reticulum Ca2+ -ATPase activity, phospholamban mRNA and
      phospholamban protein were not significantly changed compared with those in the
      control rats. At 6 and 8 weeks after the streptozotocin injection, DM rats showed
      a significant decrease in sarcoplasmic reticulum Ca2+ -ATPase activity and
      cardiac function, as indicated by an increase of LVEDP and a marked depression in
      LVSP and +/- dP/dtmax. At the same time points, increases in phospholamban mRNA
      and protein levels were observed in DM rats. Sarcoplasmic reticulum Ca2+ -ATPase
      protein level showed no significant alterations in all DM rats compared with that
      in control rats. Our work confirms that sarcoplasmic reticulum Ca2+ -ATPase
      activity is depressed in rats with streptozotocin-induced DM, which is
      accompanied by elevated phospholamban protein level thus contribute to the
      pathogenesis of cardiac dysfunction in diabetic rats.

PMID- 16909927
TI  - Dietary calcium utilization among a group of Spanish boys aged 11-14 years on
      their usual diets.
AB  - Adolescence constitutes a period of nutritional vulnerability due to increased
      dietary requirements for growth and development and special dietary habits. A
      pilot trial was performed to evaluate the dietary calcium utilization among a
      sample of Spanish boys on their usual diets, in which the calcium intake and
      consumption of dairy products were as well examined. Nutrient and food intake was
      recorded using a 24-h dietary recall and a 2-d food consumption record for 21
      subjects aged 11-14 years. Dietary calcium utilization was assessed by means of
      calcium intake in food and calcium output in faeces and urine as measured by
      flame atomic absorption spectrophotometry. Overall intake of dairy products was
      399.3 +/- 22.1 g/d, and the single most consumed item was milk (72% of the
      total). An inverse relationship was found between dairy product consumption at
      breakfast (55% of the total) and BMI (p = 0.016, r = -0.5168). Dairy products
      contributed the majority of dietary calcium (66.9%). Mean calcium intake was
      881.7 +/- 39.9 mg/d, 88% of the recommended value for Spanish adolescents. Net
      calcium absorption (271.7 +/- 51.7 mg/d) and retention (170.6 +/- 50.9 mg/d)
      seemed not to be sufficient to meet growth demands during puberty. The results
      shown that adolescents of the study absorbed 31% of dietary calcium and retained
      nearly 20% of the total intake, but dietary calcium intake and consumption of
      dairy products failed to meet recommended values. Optimizing calcium intake is of
      crucial importance among adolescents, to maximize calcium retention and to help
      prevent osteoporosis in later life.

PMID- 16909928
TI  - Effects of melatonin administration on oxidative stress and daily locomotor
      activity patterns in goldfish.
AB  - Melatonin has a number of physiological functions in addition to light-dark
      transduction. In recent years, many in vivo and in vitro studies in rodents have
      revealed an important antioxidant activity of melatonin, both directly and
      indirectly. Nevertheless, the potential effects of melatonin as an antioxidant in
      fish remain unknown. The aim of this research was to evaluate the capacity of
      melatonin injections (3 mg/kg) to attenuate oxidative damage after submitting
      goldfish to oxidative stress caused directly by hydrogen peroxide (H2O2) baths
      and indirectly by hypoxia and subsequent reoxygenation, as well as the locomotor
      activity. The results revealed that melatonin decreased lipid damage in muscle
      after hypoxia/reoxygenation (1.22 vs. 2.27 nmoles lipid peroxides/g tissue), but
      not in liver. Mortality caused by oxidative stress was not attenuated by
      melatonin. Surprisingly, melatonin caused an increase of mortality (50 vs. 95%)
      when administered before hypoxia. Locomotor activity was also affected by
      melatonin but not by the administration of the vehicle, suggesting a sedative
      effect of melatonin in goldfish. In conclusion, melatonin administration provoked
      slight effects on lipid peroxidation and mortality resulting from oxidative
      stress, with reduction of locomotor activity in relation to the vehicle.

PMID- 16909929
TI  - Plasma levels of nitrites, PGF1alpha, and nitrotyrosine in LPS-treated rats:
      functional and histochemical implications in aorta.
AB  - We investigated the effects of lipopolysaccharide (LPS) administration on plasma
      nitrite, nitrotyrosine and 6-keto prostaglandin F1alpha, (PGF1alpha) levels and
      the related resultant changes in function and histochemistry of aorta in rats.
      Plasma nitrite and PGF1alpha nitrotyrosine levels were analysed after 5 mg/kg
      intravenous LPS was administered to rats compared with those in non-treated rats.
      The distribution of nitrotyrosine in the aorta was studied immunohistochemically.
      The contractile responses of aortic rings to phenylephrine (PE) from both the LPS
      treated and control rats were studied in the organ baths. There were increases in
      plasma nitrite, PGF1alpha, and nitrotyrosine concentrations of LPS-treated rats
      compared to non-treated rats. Immunoreactivity of nitrotyrosine residues were
      detected in the endothelial and smooth muscle cells in LPS-treated but not in
      control rat aorta. The contractile responses to PE of the LPS-treated rat aortic
      rings were significantly reduced as compared with those of control rat's.
      Incubation of the aortic rings from LPS-treated rats with cyclooxygenase
      inhibitor indomethacine or with a combination of indomethacine and nitric oxide
      synthase inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) increased the
      contractile responses to the levels observed in control rats suggesting that both
      prostanoids and particularly nitric oxide (NO) are involved in the reduced
      contractile responses in LPS-treated rats. These results supported the view that
      LPS might cause an increment in both NO and PGI2 levels. This increase in the NO
      and PGI2 levels may be responsible from the reduction in responses of aorta to
      contractile agents in LPS-treated rats. Increased peroxynitrite formation in LPS
      treated rats may lead to nitration of the tyrosil residues of the proteins in the
      aorta.

PMID- 16909930
TI  - Protein kinase C cross-talk with gonadotrope progesterone receptor is involved in
      GnRH-induced LH secretion.
AB  - In the absence of progesterone (P), the anti-P at the receptor RU486 reduces
      basal and GnRH-stimulated LH secretion both in vivo and in vitro, demonstrating
      the existence of a ligand-independent activation of progesterone receptor
      (LIAPR). The aim of the present study was to determine which component of the
      intracellular LH secretory pathway activated by GnRH is responsible for LIAPR. To
      do this, anterior pituitary dispersed cells from female rats in proestrus,
      cultured in the presence of 17beta-estradiol, were incubated with activators or
      inhibitors of PKC, cAMP-PKA signalling pathways or intracellular calcium (Ca2+)
      traffic, in the presence or absence of RU486. Results showed that RU486 reduced
      both GnRH- and the PKC activator PMA-induced LH secretion. In GnRH-stimulated
      cells incubated with the PKC inhibitor BIS-I or treated with PMA "overnight",
      RU486 had no effect on reduced LH secretion, nor on stimulated LH secretion
      elicited by the Ca2+ ionophore ionomycin. Moreover, when GnRH- or PMA-treated
      cells were co-incubated with 1 microM of the L-type Ca2+ channel blocker
      nifedipine or the intracellular Ca2+ chelator BAPTA-AM, RU486 potentiated the
      expected inhibition of these drugs on LH secretion. Activation (forskolin, 8-Br
      cAMP) or inhibition (MDL-12,330A) of the cAMP-PKA signalling cascade affected
      neither the GnRH- and PMA-induced increase of LH secretion nor the reduction of
      LH secretion due to RU486. Taken together, the data point to the existence of a
      Ca2+ -independent PKC-PR cross-talk mechanism as part of the intracellular
      signalling of GnRH-stimulated LH secretion.

PMID- 16909932
TI  - A common representation for semantic and physical properties: a cognitive
      anatomical approach.
AB  - This is the first report of a mutual interference between luminance and numerical
      value in magnitude judgments. Instead of manipulating the physical size of
      compared numbers, which is the traditional approach in size congruity studies,
      luminance levels were manipulated. The results yielded the classical congruity
      effect. Participants took more time to process numerically larger numbers when
      they were brighter than when they were darker, and more time to process a darker
      number when its numerical value was smaller than when it was larger. On the basis
      of neurophysiological studies of magnitude comparison and interference between
      semantic and physical information, it is proposed that the processing of semantic
      and physical magnitude information is carried out by a shared brain structure. It
      is suggested that this brain area, the left intraparietal sulcus, subserves
      various comparison processes by representing various quantities on an amodal
      magnitude scale.

PMID- 16909933
TI  - Syllabic priming effects in picture naming in French: lost in the sea!
AB  - Ferrand, Segui, and Grainger (1996) found robust syllable priming effects in
      picture naming latencies: Pictures primed with their initial syllable (e.g., ba
      for baleine [whale]) were processed faster than pictures primed with a string of
      letters shorter or longer than their initial syllable (e.g., bal for baleine).
      However, in several studies, these priming effects have not been replicated in
      word naming or in picture naming either in Dutch or in English (Schiller, 1998,
      1999, 2000). The present study was aimed at replicating syllable priming effects
      in picture naming in French using a masked priming paradigm. The study employed a
      larger number of participants and items than were used in the Ferrand et al.
      (1996) study. The syllable priming effect in picture naming latencies was not
      replicated. Subsampling procedures were then used to examine the stability of the
      Ferrand et al. (1996) pattern of results in picture naming in greater detail. The
      syllabic priming effect in picture naming turned out to be an extremely rare
      event.

PMID- 16909931
TI  - Pathophysiology and therapeutic possibilities of calcitonin gene-related peptide
      in hypertension.
AB  - Calcitonin gene related peptide (CGRP), a 37 amino acid neuropeptide, is the most
      potent vasodilator known. Participation of CGRP in hypertension and related
      diseases, such as preeclampsia or vasospasm after subarachnoid haemorrage, is one
      of the most studied topics. In this review we summarize the published roles of
      CGRP in pathophysiology of hypertension in humans and in experimental models. We
      also discuss the effects of direct administration of CGRP in the treatment of
      hypertension and of anti-hypertensive drugs that enhance the release or response
      of endogenous calcitonin gene-related peptide: angiotensin converting enzyme
      inhibitors, selective antagonists for the angiotensin II receptor, beta-blockers,
      magnesium sulphate for preeclampsia and rutaecarpine, as well as the
      possibilities using CGRP in gene therapy for prevention of vasospasm after
      subarachnoid haemorrage.

PMID- 16909934
TI  - Stroop-like serial position effects in color naming of words and nonwords.
AB  - Color-naming latencies to noncolor words and nonwords were faster when the onset
      or final phoneme of the displays corresponded to the onset or final phoneme of
      the color response. For example, for displays printed in red, the word rack and
      nonword rask, which share the initial onset phoneme with the response, led to
      faster naming than did the control word chap and nonword chup. Conversely, when
      the onset or final phoneme of the displays matched the onset or final phoneme of
      a conflicting color response (e.g., rack printed in blue), latencies were longer
      than to control items. Facilitation effects were stronger than interference
      effects, and the onset phoneme facilitation effect was augmented by coloring only
      the initial letter in the display. It is hypothesized that nonlexical processes
      that govern the translation of print to speech may be a source of facilitation in
      Stroop-like tasks, whereas lexical processes are more likely to contribute to
      interference.

PMID- 16909935
TI  - Different interference effects in musicians and a control group.
AB  - In the present study musicians and normal control subjects performed an S1-S2
      pitch comparison task, which included the presentation of intervening tones
      during the retention interval. The time for encoding and storing the pitch of S1
      was varied between 200 and 1,500 ms by changing the pause between the S1 offset
      and the onset of the intervening tones. Although musicians outperformed the
      control group with longer pauses after the S1 offset, this advantage was
      relatively small with shorter pauses. These results suggest that the advantage of
      musicians in storing auditory information is not solely due to their superior
      encoding of information but also to improved working memory operations.

PMID- 16909936
TI  - Objects capture perceived gaze direction.
AB  - The interpretation of another person's eye gaze is a key element of social
      cognition. Previous research has established that this ability develops early in
      life and is influenced by the person's head orientation, as well as local
      features of the person's eyes. Here we show that the presence of objects in the
      attended space also has an impact on gaze interpretation. Eleven normal adults
      identified the fixation points of photographed faces with a mouse cursor. Their
      responses were systematically biased toward the locations of nearby objects. This
      capture of perceived gaze direction probably reflects the attribution of
      intentionality and has methodological implications for research on gaze
      perception.

PMID- 16909937
TI  - Working memory capacity and a notorious brain teaser: the case of the Monty Hall
      Dilemma.
AB  - The Monty Hall Dilemma (MHD) is an intriguing example of the discrepancy between
      people's intuitions and normative reasoning. This study examines whether the
      notorious difficulty of the MHD is associated with limitations in working memory
      resources. Experiment 1 and 2 examined the link between MHD reasoning and working
      memory capacity. Experiment 3 tested the role of working memory experimentally by
      burdening the executive resources with a secondary task. Results showed that
      participants who solved the MHD correctly had a significantly higher working
      memory capacity than erroneous responders. Correct responding also decreased
      under secondary task load. Findings indicate that working memory capacity plays a
      key role in overcoming salient intuitions and selecting the correct switching
      response during MHD reasoning.

PMID- 16909938
TI  - Generalization gradients for acquisition and extinction in human contingency
      learning.
AB  - Two experiments investigated the perceptual generalization of acquisition and
      extinction in human contingency learning. In Experiment 1, the degree of
      perceptual similarity between the acquisition stimulus and the generalization
      stimulus was manipulated over five groups. This successfully generated a
      generalization gradient of acquisition. In the subsequent phase, the response to
      the generalization stimulus was extinguished in each group. Finally, the
      acquisition stimulus was presented again. The response recovered differently over
      groups, thereby establishing the generalization gradient of extinction. In
      Experiment 2, the acquisition stimulus itself was extinguished before the set of
      generalization stimuli was tested between groups. One group evidenced a response
      recovery at test, which suggests that the gradient of acquisition is somewhat
      broader than the gradient of extinction.

PMID- 16909939
TI  - End-state comfort in bimanual object manipulation.
AB  - The present experiment investigated the sensitivity for end-state comfort in a
      bimanual object manipulation task. Participants were required to simultaneously
      reach for two bars and to place the objects' ends into two targets on the table.
      The design of the experiment allowed to dissociate the relative roles of initial
      means (e.g., the selection of grips) and final postures (e.g., the anticipation
      of end-states). The question of interest was whether affording different grip
      patterns for the two hands would introduce a bias away from reaching end-state
      comfort. Results revealed a strong sensitivity for end-state comfort, independent
      of the required grip patterns. In particular, end-state comfort was preferred
      even if this meant selecting different initial means (i.e., different grips) for
      the two hands. Hence, end-state oriented action planning appears to dominate
      interaction costs that may result from motor-related, intermanual interference.
      We infer that movement planning is constrained by action goals (e.g., a
      comfortable end-posture for both hands), but largely unaffected by the type of
      motor actions necessary to achieve these goals.

PMID- 16909940
TI  - Assessing anxiety with extrinsic Simon tasks.
AB  - This article introduces two new indirect measures of anxiety that are based on
      the Extrinsic Affective Simon Task (EAST; De Houwer, 2003). The EAST differs from
      the more established Implicit Association Test (IAT; Greenwald, McGhee, &
      Schwartz, 1998) in that participants' responses to different trials within one
      block of trials are compared rather than performance between two different blocks
      of trials. Two studies led to the following results: (a) Both extrinsic Simon
      tasks for assessing anxiety showed only moderate internal consistencies, (b) one
      of the two tasks showed at least some convergent validity with an IAT for
      assessing anxiety, and (c) both tasks were dissociated from self-reported
      anxiety. Implications for future adaptations of the EAST for the indirect
      assessment of personality dimensions are discussed.

PMID- 16909941
TI  - Synthesis of trimethoxy- or triethoxysilane-endcapped polylactones via a
      bismuth(III)hexanoate-catalyzed one-pot-procedure.
AB  - It was shown that bismuth(III)hexanoate (Bi(OHex)3) efficiently and selectively
      catalyzes the addition of tetra(ethylene glycol) (TEG) onto the isocyanate group
      of 3-isocyanatopropyl triethoxysilane, IPTES. delta-Valerolactone (deltaVL),
      epsilon-caprolactone (epsilonCL) and D,L-lactide were polymerized by initiation
      with TEG/Bi(OHex)3. The resulting telechelic polyesters were in situ
      functionalized with IPTES or with 3-isocyanatopropyl trimethoxysilane, IPTMS.
      Using pentaerythritol as co-initiator of Bi(OHex)3 and epsilonCL as monomer, star
      shaped polylactones having triethylsilyl end-groups were synthesized in a one-pot
      procedure. All functionalized polyesters were characterized by 1H-NMR and 13C-NMR
      spectroscopy and by MALDI-TOF mass spectrometry. Bi(OHex)3 is a remarkable
      initiator and catalyst, because of its extraordinary low toxicity.

PMID- 16909942
TI  - Morphologies of fibroblast cells cultured on surfaces of PHB films implanted by
      hydroxyl ions.
AB  - Polyhydroxybutyrate (PHB) films were implanted with 40 keV hydroxyl ions with
      fluences ranging from 1 x 10(12) to 1 x 10(15) ions/cm2, respectively. The as
      implanted PHB films were characterized by scanning electron microscopy (SEM),
      electron spectroscopy for chemical analysis (ESCA) and water contact angle
      measurements. The surface structures and properties of the as-implanted PHB films
      were closely related with hydroxyl ion fluence. They were further investigated by
      inoculating 3T6 fibroblasts cells on their surfaces. Morphologies of the 3T6
      fibroblast cells cultured on surfaces of the as-implanted PHB films were observed
      by SEM. Characterization of the cultural 3T6 cells was analyzed qualitatively.
      The preliminary experimental results reveal that the bioactivity of the PHB films
      modified by hydroxyl ion implantation was improved at different levels, and the
      fluence of 1 x 10(13) ions/cm2 is optimal for PHB film.

PMID- 16909943
TI  - Self-association and micelle formation of biodegradable poly(ethylene glycol)
      poly(L-lactic acid) amphiphilic di-block co-polymers.
AB  - Di-block co-polymers of poly(ethylene glycol)-poly(L-lactic acid) (PEG-PLLA) were
      prepared by ring-opening polymerization, and their self-association and micelle
      formation were investigated. The block co-polymers have the same block length of
      the hydrophilic PEG segment (Mn = 2000), but different chain lengths of the
      hydrophobic PLLA segment (Mn = 700, 1000 and 1300, respectively). The di-block co
      polymers synthesized were characterized by GPC, 1H-NMR, TGA and DSC. The critical
      micelle concentration (CMC) of the PEG-PLLA micelles was determined at various
      temperatures (5-45 degrees C) using a dye absorption technique involving
      fluorescence spectrophotometry with pyrene as a probe to monitor the change in
      the polarity of the microenvironment in the micelle. An increase in the molecular
      weight of the hydrophobic block decreases the CMC. The partition coefficients of
      pyrene between the micellar and aqueous phases range from 0.68 x 10(4 )to 1.76 x
      10(4), depending on the PLLA content in the block co-polymers. An Arrhenius plot
      of ln(CMC) versus 1/T exhibited an almost constant CMC at low temperatures (<35
      degrees C), followed by an increase of the CMC at higher temperatures (>35
      degrees C). The increase of the CMC with temperature indicates the increase of
      the mobility of the hydrophobic PLLA core. These results were confirmed by 1H-NMR
      measurements. The micelle size and size distribution were determined by dynamic
      light scattering (DLS), and were in the range of 78-92 nm. A spherical micelle
      shape was confirmed by transmission electron microscopy. These results indicate
      that the CMC and the thermal characteristics of the core-forming segment of the
      block co-polymer play an important role in the properties of the polymer micelles
      used for drug delivery.

PMID- 16909944
TI  - Adhesion and growth of human umbilical vein endothelial cells on collagen-treated
      PU/PEGDA IPNs.
AB  - For ideal non-thrombogenicity under normal physiologic conditions, we propose
      endothelialization. Endothelialization means that synthetic biomaterials are
      seeded by endothelial cells to mimic natural blood vessels. In our study, we
      synthesized amphiphilic polyurethane (PU)/poly(ethyleneglycol)diacrylate (PEGDA)
      interpenetrating polymer networks (IPNs) with different levels of surface energy
      to investigate the effect of adhesion and the growth of human umbilical vein
      endothelial cells (HUVECs). Collagen with cell-binding molecules was adsorbed on
      the surface of PU/PEGDA IPNs to enhance the adhesion of HUVECs. The morphology of
      collagens adsorbed on the IPN surfaces depends highly on the surface energy of
      the IPNs. As the surface becomes hydrophilic, there is greater aggregation of the
      adsorbed collagens on the IPN surface. The HUVECs successfully adhere to the
      collagen-immobilized IPN surface. The morphology of the endothelial cells (ECs)
      that adhere to IPN 2k-C and IPN 2k after 1 day and after 3 days incubation shows
      that ECs were successfully spread. The adhesion and the proliferation of ECs
      increase on non-treated IPN surfaces as the hydrophobicity of the IPNs increases.
      The surface energy of IPN 2k-C is suitable for the adhesion and proliferation of
      ECs. Therefore, platelet adhesion is significantly reduced on the EC-hybridized
      surface of IPNs.

PMID- 16909945
TI  - Adsorption of bile acid by chitosan salts prepared with cinnamic acid and
      analogue compounds.
AB  - A chitosan (CS) powder treated with cinnamic acid and an analogue compound (CN)
      was prepared as CS-CN. Using it, bile acid adsorption by CS-CN and the release of
      CN were investigated in vitro. When CS-CN was soaked in a taurocholate solution,
      it released CN and simultaneously adsorbed the bile acid. For CS-CN prepared with
      cinnamic acid, the amount of CN released was 0.286 +/- 0.001 mmol/g CS-CN; the
      amount of taurocholate adsorbed was 0.284 +/- 0.003 mmol/g CS-CN. These two
      functions were recognized on alginate or pectin gel beads containing CS-CN. The
      amount of released CN was altered extensively by the species of CN used for gel
      bead preparation. Results suggest that CS-CN is a candidate for complementary
      medicine to prevent lifestyle-related diseases.

PMID- 16909946
TI  - Bilirubin removal performance of immobilized albumin in a magnetically stabilized
      fluidized bed.
AB  - Human serum albumin (HSA)-immobilised magnetic poly(2-hydroxyethyl methacrylate)
      (mPHEMA) particles were investigated as an adsorbent for selective bilirubin
      removal from human plasma in a magnetically stabilized fluidized bed system.
      mPHEMA particles were prepared by suspension polymerization in the presence of
      Fe3O4 particles. mPHEMA particles were characterized by scanning electron
      microscopy (SEM), surface area and pore size measurements. The mPHEMA beads have
      a spherical shape and porous structure. The specific surface area of the mPHEMA
      particles was found to be 50 m2/g with a size range of 80-120 microm in diameter
      and the swelling ratio was 45%. Then, HSA was covalently coupled to the cyanogen
      bromide (CNBr)-activated mPHEMA particles. The amount of coupled HSA was arranged
      by changing the activation degree of particles (i.e., CNBr concentration). In
      vitro bilirubin removal was investigated from hyperbilirubinemic human plasma on
      the mPHEMA particles containing different amounts of immobilised HSA (between 11
      and 100 mg/g). The non-specific bilirubin adsorption on the bare mPHEMA particles
      was 0.47 mg/g. Higher bilirubin adsorption capacities, up to 88.3 mg/g, were
      obtained with the HSA-immobilised magnetic particles. Bilirubin capacity
      decreased significantly from 75.0 mg/g to 40.0 mg/g polymer with the increase of
      the flow-velocity from 0.5 ml/min to 4.0 ml/min. Bilirubin adsorption increased
      with increasing temperature. Adsorption behavior of bilirubin could be modelled
      using the Langmuir isotherm.

PMID- 16909947
TI  - Surface and chemical properties of surface-modified UHMWPE powder and mechanical
      and thermal properties of its impregnated PMMA bone cement, IV: effect of
      MMA/accelerator on the surface modification of UHMWPE powder.
AB  - In our previous study, we manufactured a reinforced poly(methylmethacrylate)
      (PMMA) bone cement with 3 wt% of the surface-modified ultra high molecular weight
      polyethylene (UHMWPE) powder to improve its poor mechanical and thermal
      properties resulting from unreacted methylmethacrylate (MMA), the generation of
      bubble and shrinkage, and high curing temperature. In the present study, the
      effect of ratios of MMA and N,N'-dimethyl-p-toluidine (DMPT) solutions in redox
      polymerization system was investigated for the surface modification of UHMWPE
      powder. We characterized physical and chemical properties of surface-modified
      UHMWPE powder and reinforced bone cements by a scanning electron microscope,
      ultimate tensile strength (UTS) and curing temperature (Tmax). It was found that
      UTSs (41.3-51.3 MPa) of the reinforced PMMA bone cements were similar to those
      (44.5 MPa) of conventional PMMA bone cement (control), as well as significantly
      higher (P < 0.05) than those (33.8 MPa) of 3 wt% unmodified UHMWPE powder
      impregnated bone cement. In particular, the UTS of redox polymerization system
      using MMA/DMPT solution was better than that of radical system using MMA/xylene
      solution. Also, Tmax of the reinforced PMMA bone cements decreased from 103 to 72
      84 degrees C. From these results, we confirmed that the surface-modified UHMWPE
      powder can be used as reinforcing agent to improve the mechanical and thermal
      properties of conventional PMMA bone cement.

PMID- 16909948
TI  - Preparation and properties of invertase immobilized on a poly(maleic anhydride
      hexen-1) membrane.
AB  - Poly(maleic anhydride-alt-hexen-1)(poly(MA-alt-H-1)) has been synthesized by
      radical polymerization and characterized by DSC, FT-IR, acid number
      determination, viscometric and NMR methods. Data showed that the co-polymer is an
      alternating co-polymer whose composition does not depend on the monomer feed
      composition. Invertase was immobilized onto a poly(MA-alt-H-1) membrane via
      glutaraldehyde and bovine serum albumin. The Km value of poly(MA-alt-H-1)
      invertase was approximately 4.4-fold higher than the free enzyme, indicating
      decreased affinity by the invertase for its substrate (sucrose), whereas Vmax was
      lower for the immobilized invertase. Immobilization improved the pH stability of
      the enzyme, as well as its temperature stability. Immobilized samples obtained
      were stable and could be used many times over a period of 2 months without
      considerable activity loss.

PMID- 16909949
TI  - [Epidemiologists need more time to work properly].

PMID- 16909950
TI  - [Economics vs precaution: responding to the critique].

PMID- 16909951
TI  - [Syndial offers reimbursement to women of Augusta-Prioli (Sicily) who had
      abortions or malformed babies].

PMID- 16909952
TI  - [Quito: South and North of the globe meet to talk about health, work and
      environment in developing countries].

PMID- 16909953
TI  - [Mortality for non-Hodgkin lymphoma in the period 1981-2000 in 25 Italian
      municipalities with urban solid waste incinerators].

PMID- 16909954
TI  - [Work and prevention in the People's Republic of China].

PMID- 16909955
TI  - [Health in the school: experimental work in progress].

PMID- 16909956
TI  - [Preliminary analysis of indoor pollution from nitrogen dioxide in an area of
      Northern Italy].
AB  - OBJECTIVE: The aims of this work are to describe the annual mean concentration of
      NO2 and to identify the home features and "habits" of its occupants related to
      NO2 levels. Both indoor and outdoor NO2 concentrations were measured in 114
      dwellings in Pavia (Northern Italy). DESIGN: The study is in the frame of
      European Community Respiratory Health Survey II. Data were collected in the
      period 2001-2002 during home visits by trained fieldworkers. PARTICIPANTS: 116
      subjects gave the consent to home visits. MAIN OUTCOME MEASURE: NO2 concentration
      measured using passive samplers. RESULTS: Indoor NO2 concentration is in average
      47.1 microg/m3 (+/- 24.5 microg/m3) and outdoor NO2 concentration is 44.3
      microg/m3 (+/- 14.5 microg/m3). The gas oven is the only domestic gas appliance
      associate with high levels of NO2 when measuring in homes. The outdoor pollution
      affects NO2 indoor concentrations and contribute to store NO2 in homes.
      CONCLUSION: the study is the first step in the evaluation of NO2 exposure effect
      on respiratory health.

PMID- 16909957
TI  - [Gender difference and mortality in a cohort of heroin users in the Provinces of
      Modena and Ferrara, 1975-1999].
AB  - OBJECTIVE: To analyse overall and cause-specific hazards of death in a cohort of
      heroin users, separately by gender, survival and other risk factors. DESIGN AND
      SETTING: Longitudinal study of intravenous heroin users; subjects were enrolled
      between 1975 and 1999 in public health services of the Provinces of Modena and
      Ferrara and were included in a treatment program. MAIN OUTCOME MEASURES: For each
      gender, age-standardized mortality rates and standardized mortality ratios (SMR)
      for all causes and for specific causes. Kaplan-Meier method was used for
      estimating survival probability and Cox regression model to estimate hazard
      ratios (HR) of death. RESULTS: in the cohort of 4.644 intravenous drug users, 801
      deaths were observed. In both sexes, mortality due to AIDS was lower in subjects
      enrolled in 1990-99 than among those enrolled in 1980-89. Mortality caused by
      overdose was particularly high in males enrolled between 1995-99. (SMRs in males
      and females were respectively 12.12 (95% CI 11.22-13.08) and 20.26 (17.23-23.83).
      Survival probability at 20 years of observation was 62% (60% for males and 68%
      for females). Risk of death was highest in males, in subjects enrolled after age
      25, in subjects with a low educational level and in unemployed persons.
      CONCLUSION: Gender and socioeconomic conditions are important determinants of
      mortality among heroin users. The increase in deaths from heroin overdose in
      subjects enrolled in the recent years requires particular attention.

PMID- 16909958
TI  - [Polychlorinated biphenyl serum levels in two Italian population groups: sex
      pattern and correlation with age].
AB  - OBJECTIVE: To examine the congener-specific concentrations and patterns of
      polychlorinated biphenyls in the Italian general population. DESIGN: Two
      population groups were selected and monitored for the determination of up to 60
      congeners in human serum. A very detailed questionnaire was administered to each
      participant to collect information concerning demographic, lifestyle, and medical
      factors. Statistical analyses were performed to examine the relationships between
      PCB serum levels and age. SETTING: Northern and Central Italy. PARTICIPANTS: 162
      subjects from Novafeltria, Central Italy and 164 subjects from Pavia, Northern
      Italy. MAIN OUTCOME MEASURE: Serum concentrations of both coplanar and non
      coplanar PCB congeners. Relationship between PCB levels and age. RESULTS: The
      mean concentration of total PCBs was found to be 2.48 and 3.93 microg/l for
      Novafeltria and Pavia, respectively. As waited, the most abundant congeners were
      CB-153, CB-138, CB-180, and CB-170. Age resulted to be the most significant
      determinant of PCB levels. Slight differences in the congener profile were
      observed in the two population groups. CONCLUSIONS: As expected, a strong
      correlation between age and PCB levels has been observed. It is remarkable that
      the correlation increased with increasing chlorination in both the population
      groups. Associations with other variables, such as gender, food and alcohol
      consumption, and cigarette smoking, appeared to be inconsistent.

PMID- 16909959
TI  - [Increase in mortality for motor neuron disease in Italy, 1980-1999].
AB  - OBJECTIVE: To describe the mortality rates for motor neuron disease (MND) in
      Italy both at national level and at three large geographical sub-areas (Northern,
      Central, Southern Italy). DESIGN: Deaths for MND are coded accordingly to ICD (IX
      revision) with 335.2 code. Mortality for MND is analysed for the period 1980-99.
      Mortality rates are age-standardized on the structure of the 1991 Italian
      population. Mortality data are derived from the National Institute for Statistics
      (ISTAT) and are made available by the Epidemiological Database of the Italian
      National Agency for New Technologies, Energy and the Environment (ENEA). MAIN
      OUTCOME MEASURES: Age adjusted mortality rates for MND are calculated for 5-year
      periods (1980-84, 1985-89, 1990-94, 1995-99) at both national level and three
      geographical sub-areas (north, center and south); sex and age specific mortality
      rates are also reported for two decades (1980-89 and 1990-99). RESULTS: During
      1980-99 the annual age-standardized mortality rate in Italy was 1.35 x 100000 in
      males and 1.10 (x 100000) in females. In the period 1995-99 the mortality rates
      increased by 39.3% in males and 78.2% in females at national level when compared
      to 1980-84 rates (1.56 vs 1.12 deaths per 100000 for males and 1.39 vs 0.78 per
      100000 for females in 1980-84 and 1995-99, respectively). In the three large
      geographical sub-areas such increases were 37.6%, 29.7% and 57% in males and 73%,
      63.1% and 114.3% in females, respectively. CONCLUSION: The increase reported in
      this study is probably due to a mix of different factors as population ageing
      (age-specific rates reach a peak in the age class 70-74 years), better accuracy
      of death certificates, adoption of new clinical criteria and at last a wide
      spread of environmental risk factors (metals, solvents, pesticides,
      electromagnetic fields) and modification of life style (smoking, diet,
      professional sport).

PMID- 16909960
TI  - [Cancer incidence in Modena: 2002-2006 projections].
AB  - OBJECTIVE: Cancer incidence predictions for the period 2002-2006 in the Province
      of Modena applying a Bayesian APC (Age Period Cohort) model. DESIGN: Population
      based descriptive study. SETTING: Patients with cancer diagnosed between 1988 and
      2001 recorded in Modena Cancer Registry. MAIN OUTCOME MEASURES: Number of cases,
      crude and standardized incidence rates. RESULTS: Cancer incidence in 2002-2006 is
      expected to increase in both sexes, with the exception of stomach cancer (males
      and females) and lung cancer in males, both expected to decrease. The difference
      between the number of cases predicted for 2002 and observed data was about 0.7%.
      CONCLUSION: Prediction based on APC model seems to be reliable for most of the
      cancer sites, but should be used cautiously. In particular, projected number of
      breast and prostate cancer cases is clearly overestimated due to diagnostic
      anticipation effect which gives rise to an excess in recent years.

PMID- 16909961
TI  - [Mortality in the area around Massa-Carrara 10 years after ANIC-Agricoltura and
      Farmoplant chemical plants were shut down].
AB  - OBJECTIVE: To describe mortality of residents in the area of Massa-Carrara for
      the period 1995-2000 and to compare it with mortality for the years 1990-1994.
      DESIGN: Geographical descriptive study. SETTING: In the area of Massa-Carrara
      cause and gender specific standardized mortality ratios (SMR), adjusted for age
      and municipal deprivation index (reference: Tuscany Region), have been computed
      for the years 1995-2000 and compared with mortality in the period 1990-1994
      calculating ratios between standardized rates by age classes with a direct method
      (CMF). For those causes showing a statistically significant increase a spatial
      analysis on a group of municipalities around Massa and Carrara has been carried
      out. MAIN OUTCOME: Mortality for all causes, and for 30 specific causes. RESULTS:
      The study results confirm, for the years 1995-2000, the previous observation
      (1990-1994) of statistically significant excesses for mortality from all causes
      (SMR 109), all cancers (SMR 112), respiratory diseases (SMR 126), cirrhosis (SMR
      226), liver (SMR 161) and lung cancer (SMR 115) in males. A statistically
      significant excess for larynx (SMR 158) and pleural cancer (SMR 178) is observed
      in the years 1995-2000, which was not present in 1990-1994. A mortality excess
      for cirrhosis is confirmed in females (SMR 158) and a new one emerges for liver
      cancer (SMR 144). The comparison between mortality data for the periods 1995-2000
      and 1990-1994 has shown a statistically significant decrease in mortality for all
      causes and for several specific causes, a significant increase in liver (CMF
      males 1.35; CMF females 1.78) and blood cancer mortality is also detected (CMF
      females 1.44). CONCLUSIONS: This study confirms the negative health impact of
      environmental, occupational exposures in populations living in areas where high
      risk factories are located. Adverse health effects are stronger in socially and
      economically deprived areas, and persist over many years after closing polluting
      industrial plants. The results of this study point out to the need of health
      promoting actions aiming at modifying lifestyle risk factors, ameliorating socio
      economic conditions, and maintaining a constant control on environment, also
      through a specific environmental epidemiological surveillance to monitor the
      impact of reclamation procedures completed or in progress.

PMID- 16909962
TI  - [From research to users: the Worksafe European Project and the IST-Gaslini
      Prevention and Safety Project].
AB  - OBJECTIVE: The Worksafe Project aims at increasing access to and use of the large
      amount of data related to the broad sector of health protection of workers and
      workplace safety recognising the key role of the communication and dissemination
      of the research results with particular reference to cancer. PARTICIPANTS: Four
      scientific institutes: National Institute for Research on Cancer, Genoa (IST);
      Finnish Institute of Occupational Health (FIOH), Helsinki; Karolinska Institutet
      (KI), Stockholm; International Agency for Research on Cancer (IARC), Lyon, and
      two technological partners (Softeco Sismat, Genoa; Fundacion Robotiker, Bilbao).
      RESULTS: The creation of the Worksafe portal, a web based infrastructure that
      allows knowledge sharing on top of a distributed digital data collection and
      provides web accessed services addressing a broad interested audience including
      biomedicine companies universities, research institutions, local and national
      public organisations and private users.

PMID- 16909963
TI  - [Use of discharge records to define the oncological diagnoses for outpatient
      radiotherapy patients].
AB  - OBJECTIVE: Outpatient activity recording system has a potential role in clinical
      practice evaluation. Nevertheless, up to now, its utilisation has been limited by
      the paucity of its clinical data. This study describes a procedure for
      identifying the oncological diagnosis in patients receiving radiotherapy at an
      ambulatory service in the Piedmont Region. The procedure is based on the record
      linkage between discharge records (SDO) and outpatients records (PA), in order to
      obtain clinical information from the diagnosis related to possible admissions of
      the patients. METHODS: The study analyzed radiotherapy outpatients records in
      2003 related to Piedmont residents and all discharge records in years 2000-2004.
      The quality of the procedure has been assessed by using the information on the
      real oncological diagnosis as reported in the outpatients medical records of a
      random sample of patients. RESULTS: The record linkage with SDO allows to define
      an oncological diagnosis for 82% (95% CI 78.5-84.8) of the patients. Agreement
      between defined diagnosis and the real one is 85.7% (CI 95% 82.2-88.6). The
      validity of the procedure is affected by the patients' cancer site. The
      distribution by cancer site of the patients treated with radiotherapy in Piedmont
      Region obtained with the record linkage procedure is homogeneous to the real
      distribution of the random sample used for control. CONCLUSIONS: Overall, the
      record linkage between SDO and radiotherapy PA shows a good performance in
      defining the oncological diagnosis of the patients receiving radiotherapy at an
      ambulatory setting. This method allows to increase interest and utility of PA
      records.

PMID- 16909964
TI  - The combination of raltitrexed (Tomudex) and mitomycin-C in the treatment of
      advanced colorectal cancer--a phase II study.
AB  - AIMS: To investigate the combination of raltitrexed and mitomycin-C as first-line
      chemotherapy treatment in patients with advanced colorectal cancer. MATERIALS AND
      METHODS: A phase II study. RESULTS: In total, 22 patients were treated with a
      combination of raltitrexed 3 mg/m2 every 3 weeks and mitomycin-C 7 mg/m2 every 6
      weeks for up to 24 weeks. The study was closed early for safety reasons as there
      were three unexpected treatment-related deaths. The overall response rate was
      20%, and a further 40% achieved stable disease. The median time to progression
      was 3.9 months and the median overall survival time was 11.6 months. CONCLUSION:
      Owing to the potential for increased toxicity, the combination of raltitrexed and
      mitomycin-C cannot be recommended as first-line treatment in patients with
      advanced colorectal cancer.

PMID- 16909965
TI  - Smoking compromises cause-specific survival in patients with operable colorectal
      cancer.
AB  - AIMS: To assess whether active smoking compromises survival in patients with
      colorectal cancer. MATERIALS AND METHODS: We studied a regionally based cohort of
      284 consecutive patients referred to the Tayside Cancer Centre for consideration
      of adjuvant treatment after curative surgery for colorectal cancer. RESULTS:
      Cause-specific survival was significantly worse (P = 0.0015) in patients who were
      actively smoking at the time of their first post-operative visit. The absolute
      difference in 5-year cause-specific survival (active smokers vs the rest) was
      21%. In adjusted multi-variate analysis of patients after pathologically complete
      (R0) resection, the hazard ratio was 2.55 (95% confidence interval 1.40-4.64) in
      active smokers compared with non-smokers. T stage, number of positive nodes and
      co-morbidity score were also of independent prognostic influence. CONCLUSIONS:
      Persistent smoking was, in this small series, an important and independent
      predictor of cancer-related death after surgery for cancer of the large bowel.
      Because smoking and deprivation are related, some of the adverse effects of
      deprivation upon survival in this group of patients may be explained by smoking
      behaviour.

PMID- 16909966
TI  - The effect of belly board location in rectal cancer patients treated with
      preoperative radiotherapy.
AB  - AIMS: To evaluate the effect of the belly board aperture location on the
      irradiated small bowel volume in rectal cancer patients treated with preoperative
      pelvic radiotherapy. MATERIALS AND METHODS: Twenty patients with rectal cancer
      scheduled to receive preoperative pelvic radiotherapy were evaluated
      prospectively. Each patient underwent computed tomography with the belly board
      aperture lower border at three different locations relative to patient anatomy:
      the lumbosacral junction (location I), the lower end of the sacroiliac joint
      (location II) and the upper end of the symphysis pubis (location III). The
      irradiated small bowel volume was calculated for doses between 10 and 100% of the
      prescribed dose at 10% intervals. For each 10% dose increment, the effect of the
      belly board aperture at the three different locations on the irradiated small
      bowel volume was analysed using Wilcoxon signed rank and Wilcoxon rank sum tests.
      RESULTS: At 10-20% dose levels, the irradiated small bowel volume increased in
      the order of locations I, II and III, and the differences between each location
      were significant. At > or = 30% dose levels, the irradiated small bowel volume
      increased in the order of locations III, II and I, and the differences between
      locations I and II were significant, but the differences between locations II and
      III were not significant. CONCLUSION: The belly board aperture location can
      influence the irradiated small bowel volume differently at each dose level. When
      considering the use of a belly board in routine clinical practice, we recommend
      that the clinician take into account the patterns of irradiated small bowel
      volume according to belly board aperture location.

PMID- 16909967
TI  - Wide local excision and radiotherapy for the treatment of ductal carcinoma in
      situ of the breast: the Hong Kong experience.
AB  - AIMS: Breast conservation treatment for ductal carcinoma in situ (DCIS) was
      unpopular in the Chinese population and the outcome was seldom reported. We
      conducted a single-centre retrospective study to examine the clinical outcome of
      women in Hong Kong. MATERIALS AND METHODS: Seventy-five Chinese women were
      treated with wide local excision and radiotherapy for DCIS of the breast between
      1994 and 2003. Only 26 (34.7%) women had non-palpable DCIS detected by screening
      mammograms. All women were treated with whole breast irradiation of 50 Gy in 2 Gy
      daily fractions, with 50 (66.7%) women receiving an additional electron boost of
      10-16 Gy. RESULTS: The median follow-up was 5.1 years (range 2.0-10.7). At the
      last assessment, four women developed local recurrences, but all remained disease
      free after salvage mastectomy. The 5-year actuarial local failure-free rate and
      cause-specific survival rate were 92.9% (95% confidence interval 89.4-96.4) and
      100.0%, respectively. Cosmetic results were rated as good to excellent in all
      women. On univariate analysis of prognostic factors for local failure, only a
      close (< or = 2 mm) final resection margin approached statistical significance
      (hazard ratio 9.108; 95% confidence interval 0.946-87.655; P = 0.056). The 5-year
      actuarial local failure-free rates for women with a close (< or = 2 mm) final
      resection margin and women with wider margins were 77.0 and 98.2%, respectively.
      CONCLUSIONS: Despite geographical and demographic differences, the clinical
      outcome after wide local excision and radiotherapy for DCIS of the breast in
      Chinese women is comparable with that in Western series. Efforts are needed to
      achieve cosmetically acceptable tumour-free margins greater than 2 mm.

PMID- 16909968
TI  - Pre-treatment haemoglobin levels and the prediction of response to neoadjuvant
      chemotherapy in breast cancer.
AB  - AIMS: A low pre-treatment haemoglobin level has been shown to negatively
      influence outcome in the treatment of tumours of the cervix, bladder and head and
      neck by radiotherapy. The purpose of this study was to assess the influence of
      baseline haemoglobin levels on the response to neoadjuvant chemotherapy for
      breast cancer. MATERIALS AND METHODS: One hundred and thirty-nine women receiving
      neoadjuvant chemotherapy for operable breast tumours (T2-4, N0-1, M0) were
      accessed from our prospective database. Women were treated between March 1999 and
      June 2004. The median age was 47 years (range 25-70). Most women were treated
      with 5-fluorouracil, epirubicin and cyclophosphamide chemotherapy (122/139
      patients). Baseline haemoglobin levels were compared for clinical responders
      (partial or complete) and non-responders (stable or progressive disease) using
      Student's t test and logistic regression. The analysis was adjusted for nodal
      status, tumour size, tumour grade and menopausal status. RESULTS: The overall
      response rate was 84.9% (118/139), with a complete clinical response in 24.5%
      (34/139). Mean haemoglobin levels were 13.3 g/dl in responders and 13.4 g/dl in
      non-responders (range 7.9-15.8). The distributions of haemoglobin levels were not
      significantly different when comparing either responders with non-responders or
      'good' responders with 'poor' responders (P = 0.70 and P = 0.32, respectively).
      If haemoglobin is treated as a binary variable using 12.0 g/dl as the threshold,
      there is a non-significant trend towards a reduction in the probability of
      achieving a good response if baseline haemoglobin is below 12.0 g/dl (odds ratio
      = 0.26, confidence interval = 0.06-1.21; P = 0.086). The rate of complete
      pathological response was 4.3% (6/139). The mean haemoglobin level in these
      patients was 14.2 g/dl (range = 12.8-15.7), but the small numbers precluded
      further analysis. CONCLUSIONS: There is no evidence for an influence of pre
      treatment haemoglobin levels on the clinical response to neoadjuvant chemotherapy
      in breast cancer. It is unlikely that correction of anaemia above that which is
      warranted clinically will improve outcomes.

PMID- 16909969
TI  - Age and bromodeoxyuridine labelling index as prognostic factors in high-grade
      gliomas treated with surgery and radiotherapy.
AB  - AIMS: To determine the prognostic value of proliferative potential and DNA ploidy
      in 72 brain tumours (36 grade III and 36 grade IV astrocytomas) using
      bromodeoxyuridine (BrdUrd) incorporation and flow cytometry. MATERIAL AND
      METHODS: All 72 patients underwent excision, mostly incomplete of the tumour.
      After surgery, eight patients received conventionally fractionated radiotherapy,
      11 patients received accelerated radiotherapy, and 53 patients received
      hypofractionated radiotherapy. Tumour samples taken during surgery from each
      patient were incubated in vitro for 1 h at 37 degrees C with BrdUrd using the
      high pressure oxygen method. The percentage of BrdUrd-labelled cells (BrdUrd
      labelling index [BrdUrd LI]), and the total DNA content were evaluated: RESULTS:
      The tumours showed variability in the BrdUrd LI values, which ranged from 0.3 to
      19.1%. No difference was observed in mean BrdUrd LI between grade III and grade
      IV sub-groups. A significantly higher percentage of DNA aneuploidy was observed
      in grade III gliomas (69.4%) than in grade IV gliomas (52.8%). Univariate
      analysis showed that younger patients (< or = 51 years) (P = 0.021) with grade
      III gliomas (P = 0.030) and low tumour proliferation rate (BrdUrd LI < or = 2.7%,
      P = 0.028) had significantly higher 5-year survival rates. Tumour ploidy had no
      influence on patients' survival (P = 0.591). However, Cox multi-variate analysis
      showed that only age over 51 years, and high tumour proliferation rate (BrdUrd LI
      > 2.7%), were significant unfavourable prognostic factors in patient survival.
      CONCLUSION: In this study, independent prognostic factors for patients with high
      grade gliomas treated with surgery and post-operative radiotherapy are age and
      tumour proliferation rate assessed according to the BrdUrd LI.

PMID- 16909970
TI  - Evaluating the effect of reducing the high-dose volume on the toxicity of
      radiotherapy in the treatment of bladder cancer.
AB  - AIMS: The radiation dose used to treat bladder cancer is limited by the risk of
      inducing severe late bladder toxicity. Retrospective data suggest that radiation
      tolerance is greater for partial rather than whole bladder irradiation. Limiting
      the high-dose region to a section of the bladder may reduce toxicity, opening the
      way for dose escalation. The aims of this study were to establish the efficacy
      and compare the late toxicity between (1) a two-phase technique limiting the high
      dose area and (2) a conventional single-phase radiotherapy to the whole bladder.
      MATERIALS AND METHODS: A cohort study was undertaken of 229 patients with
      invasive bladder cancer treated with computed tomography-planned radical
      radiotherapy at the Royal Marsden Hospital from 1984 to 1998. In total, 154
      patients received a single-phase treatment to the whole bladder with a 2 cm
      margin. Seventy-five patients with solitary, well-localised tumours were selected
      for treatment using a two-phase technique. The first phase (12 Gy) aimed to treat
      the tumour with a 2 cm margin. A second phase treated the whole bladder with 52
      Gy. One hundred and forty-one patients were planned to receive a dose of 60-64
      Gy/30-32 fractions over 6-6.5 weeks, whereas 88 patients received an accelerated
      regime. Data on late bladder and bowel toxicity (using Radiation Therapy Oncology
      Group criteria) were collected prospectively at the annual review. RESULTS: At
      the 5-year follow-up there was no difference in overall survival (hazard ratio =
      0.91, 95% confidence interval 0.64-1.3) or failure-free survival (hazard ratio =
      1.02, 95% confidence interval 0.73-1.43) between the two techniques. The two
      phase reduced volume treatment was less toxic, with a 19% absolute reduction in
      overall grade 3-4 late toxicity (P = 0.02). These differences were more marked
      for bladder toxicity compared with bowel toxicity. CONCLUSIONS: The two-phase
      reduced volume technique was associated with less bladder and bowel toxicity than
      conventional whole bladder radiotherapy without evidence of impaired survival.

PMID- 16909972
TI  - Diagnosis of bone metastasis in men with prostate cancer by measurement of serum
      ICTP in combination with alkali phosphatase and prostate-specific antigen.
AB  - AIMS: Carboxy-terminal telopeptide of type I collagen (ICTP) is a parameter of
      bone absorption, and has recently been introduced to monitor bone metastases. The
      aim of this retrospective study was to investigate the potential of ICTP as a
      candidate serum marker of bone metastasis in prostate cancer. MATERIALS AND
      METHODS: Serum markers in 155 men pathologically diagnosed with prostate cancer
      were measured. The serum levels of ICTP, prostate-specific antigen (PSA), and
      alkali phosphatase (ALP) were compared to assess the extent of disease (EOD)
      scores from bone scans and then analysed statistically. RESULTS: The serum ICTP
      levels were not well correlated with the EOD scores in the total group of men,
      men newly diagnosed with prostate cancer, or men previously diagnosed with
      prostate cancer who were followed up. The sensitivity, specificity, positive
      predictive value (PPV) and negative predictive value (NPV) of ICTP (cut-off
      value, 5.0 ng/ ml) of the men newly diagnosed with prostate cancer were 78.6%,
      88.0%, 78.6%, and 88.0%, respectively. In these men, the specificity and PPV of
      ALP (cut-off value, 335 IU/l) were 100%, whereas the sensitivity and NPV of PSA
      (cut-off value, 40 ng/ml) were 100% in this study. The serum levels of ICTP in
      the men with low ALP (< 335 IU/l) and high PSA (> or = 40 ng/ ml) clearly
      separated the men with or without bone metastasis, as judged by bone scans.
      CONCLUSION: We found that the ICTP is not a superior serum marker for bone
      metastases compared with ALP or PSA. Our study suggests, however, that the ICTP
      measurement is useful in a certain subset of men with the combination of PSA and
      ALP in distinguishing men with bone metastasis from those without.

PMID- 16909971
TI  - High dose rate iridium-192 brachytherapy as a component of radical radiotherapy
      for the treatment of localised prostate cancer.
AB  - AIMS: To assess the treatment outcomes and toxicity of conformal high dose rate
      (HDR) brachytherapy boost as a means of radiation dose escalation in patients
      with localised prostate cancer. MATERIALS AND METHODS: Between December 1998 and
      July 2004, 65 consecutive patients with localised prostate cancer (magnetic
      resonance imaging-staged T1-3 N0 M0) were treated with external beam radiation
      therapy (EBRT) followed by two fractions of HDR iridium-192 brachytherapy. The
      patients selected this treatment modality in preference to entering an ongoing
      randomised phase 3 trial. Any pre-treatment serum prostate-specific antigen (PSA)
      and Gleason score were included. The primary end point was biochemical disease
      free progression. Late treatment-related morbidity was graded according to the
      Radiation Therapy Oncology Group and the European Organization for Research and
      Treatment of Cancer criteria. RESULTS: The median patient age was 67.3 years
      (range 47.9-80). Sixty patients (92.3%) had intermediate- to high-risk disease
      defined by clinical stage, presenting PSA and Gleason score/World Health
      Organisation (WHO) grade. With a median follow-up of 3.5 years (range 0.6-5.8),
      two patients had died of metastatic disease and another four patients had PSA
      relapse, giving a 3-year actuarial biochemical disease-free progression of 90.8%.
      Three patients (4.6%) had acute grade 3 genitourinary toxicity, in the form of
      urinary retention. Late grade 3 and 4 genitourinary toxicities occurred in four
      patients (6.2%) and one patient (1.5%), respectively. No late gastrointestinal
      toxicities were observed. CONCLUSIONS: These results suggest that the combined
      modality of conformal HDR brachytherapy and EBRT is a feasible treatment modality
      with acceptable acute and late toxicities, comparable with those of EBRT alone.
      It offers an attractive conformal treatment modality with the potential of
      further dose escalation in the treatment of localised prostate cancer.

PMID- 16909973
TI  - Compensator-based intensity-modulated radiotherapy in head and neck cancer: our
      experience in achieving dosimetric parameters and their clinical correlation.
AB  - AIMS: To review the Batra Hospital and Medical Research Centre experience of
      using compensator-based intensity-modulated radiotherapy (IMRT) to treat head and
      neck cancer. MATERIALS AND METHODS: Between October 2003 and August 2004, 18
      patients underwent IMRT for head and neck cancer at our institution. IMRT was
      delivered using partial transmission high-resolution compensator blocks. RESULTS:
      With a median follow-up of 13.3 months, two patients had residual disease and two
      failed in the gross tumour volume (GTV). The complete response rate after
      surgical salvage was 94.5%. Both the locoregional relapse-free and disease-free
      survival rates were 81.8%. The target coverage in terms of average maximum, mean
      and minimum dose (in Gy) delivered was 78.6, 73.5 and 58.4 to the GTV-planning
      target volume, 82.3, 70.9 and 47.3 to clinical target volume 1 (CTV1) and 82.9,
      66.2 and 29.6 to CTV2. The dose constraint of 30 Gy to less than 50% of the
      contralateral parotid volume was achieved in 12 (66.7%) patients. If the dose
      constraint was revised to 35 Gy, at least 50% of the parotid volume was spared in
      17 (94.5%) patients. On average, 75% of the contralateral parotid volume received
      a dose less than 35 Gy in 13 (72.3%) patients with grade I xerostomia, whereas
      this was 49.3% in five (27.7%) patients with grade II xerostomia, and the
      difference was statistically significant (P = 0.001). CONCLUSIONS: In our initial
      experience, compensator-based IMRT is feasible with regard to target coverage and
      parotid volume sparing. The parotid volume dose has significant clinical
      implications on the grade of xerostomia. Our results invoke rethinking into the
      issues of the parotid volume dose constraint in our subpopulation.

PMID- 16909974
TI  - Carbogen breathing combined with radical radiotherapy in advanced head and neck
      cancer patients with severe co-morbidities.
AB  - AIMS: To assess the feasibility of carbogen breathing combined with radical
      radiotherapy in patients with advanced head and neck cancer who are unfit to
      receive concomitant chemotherapy. MATERIALS AND METHODS: Twenty patients (median
      age 66 years) with advanced squamous cell carcinoma of the head and neck were
      treated with either concomitant boost radiotherapy (75%) or mono-fractionated
      radiotherapy (25%) combined with carbogen breathing. The median tumour dose was
      69.5 Gy. The main sites of disease were the oropharynx in 50%, the oral cavity in
      15% and the hypopharynx in 30%. All but one patient had stage III (25%) or IV
      (70%) disease. The median follow-up for the surviving patients was 26 months
      (range 6-50 months). RESULTS: Carbogen breathing was well tolerated, permitting
      its delivery throughout the radiotherapy course. Three patients had treatment
      interruption because of acute toxicities (median 15 days; range 3-30 days). Grade
      3 Radiation Therapy Oncology Group acute toxicity was observed in 80% of the
      patients (mainly mucositis), and nutritional support was required in eight
      patients (40%). Grade 2 late toxicity occurred in 30%; one patient presented with
      grade 4 late toxicity (bone necrosis). The 2-year actuarial locoregional control
      for all patients and for those treated with accelerated radiotherapy was 56% and
      67%, respectively. The corresponding rates for disease-free survival were 45% and
      53%. CONCLUSIONS: Considering the poor results of radiotherapy alone in advanced
      head and neck cancer, these results suggest that carbogen breathing may be a
      valid alternative for patients with severe co-morbidities who are unfit to
      receive concomitant chemotherapy.

PMID- 16909975
TI  - Can dose reduction to one parotid gland prevent xerostomia?--A feasibility study
      for locally advanced head and neck cancer patients treated with intensity
      modulated radiotherapy.
AB  - AIMS: Dryness of the mouth is one of the most distressing chronic toxicities of
      radiation therapy in head and neck cancers. In this study, parotid function was
      assessed in patients with locally advanced head and neck cancers undergoing
      intensity-modulated radiotherapy (IMRT) with or without chemotherapy. Parotid
      function was assessed with the help of a questionnaire and parotid scintigraphy,
      especially with regards to unilateral sparing of the parotid gland. MATERIALS AND
      METHODS: In total, 19 patients were treated with compensator-based IMRT between
      February 2003 and March 2004. The dose to the clinical target volume ranged
      between 66 and 70 Gy in 30-35 fractions to 95% of the isodose volume. Ipsilateral
      high-risk neck nodes received an average dose of 60 Gy and the contralateral low
      risk neck received a dose of 54-56 Gy. Eight of 19 patients also received
      concomitant chemotherapy. RESULTS: Subjective toxicity to the parotid glands was
      assessed with the help of a questionnaire at 0, 3 and 6 months and objective
      toxicity was assessed with parotid scintigraphy at 0 and 3 months. The mean dose
      to the ipsilateral parotid gland ranged from 19.5 to 52.8 Gy (mean 33.14 Gy) and
      the mean dose to the contralateral gland was 11.1-46.6 Gy (mean 26.85 Gy). At a
      median follow-up of 13 months, 9/19 patients had no symptoms of dryness of the
      mouth (grade I), 8/19 had mild dryness of the mouth (grade II) and only 2/19 had
      grade III xerostomia, although the parotid gland could only be spared on one side
      in most of the patients. CONCLUSIONS: Minimising the radiation dose to one of the
      parotid glands with the help of IMRT in patients with advanced head and neck
      cancers can prevent xerostomia in most patients and parotid scintigraphy is a
      useful method of documenting xerostomia.

PMID- 16909976
TI  - Neurone-specific enolase and liver metastasis in small cell lung cancer.

PMID- 16909977
TI  - Intrapericardial instillation of mitomycin C in recurrent cardiac tamponade due
      to malignant pericardial effusion.

PMID- 16909978
TI  - Acquired C1-esterase deficiency and optic neuropathy in non-Hodgkin's lymphoma.

PMID- 16909979
TI  - Carnosine protects from the oxidative stress induced by prenatal hypoxia.

PMID- 16909980
TI  - A new approach to making autoprostheses for angioplasty.

PMID- 16909981
TI  - Cryoconservation of seeds of rare Russian orchids.

PMID- 16909982
TI  - The role of biotic relationships in biological invasions as exemplified by
      zooplanktonic communities.

PMID- 16909983
TI  - Nerve cells in the digestive tract epithelium of gastropods.

PMID- 16909984
TI  - Species-specific stimulation of cyanobacteria by silver carp Hypophthalmichthys
      molitrix (Val.).

PMID- 16909985
TI  - Conjugation transfer of chromosomal and plasmid genes in Bacillus subtilis.

PMID- 16909986
TI  - "Hollows" in the spatial distribution of earthworms in a meadow steppe.

PMID- 16909987
TI  - The fractal structure of the percolation cluster and the spatial distribution of
      dominant species.

PMID- 16909988
TI  - Two types of genetic differentiation in the evolution of sibling species of the
      spiny rats from genus Proechimys native to Upper Amazonia.

PMID- 16909989
TI  - Self-oscillations of concentrations as a possible cause of overdominant
      interactions of allozyme genes.

PMID- 16909990
TI  - The adaptive mechanism of sex reversal in populations of pink salmon
      (Oncorhynchus gorbuscha).

PMID- 16909992
TI  - Annual photosynthetic carbon sequestration and net ecosystem production in
      northern Eurasian plant cover.

PMID- 16909991
TI  - The matrix protein of human immunodeficiency virus is cleaved and packed into
      virion cores.

PMID- 16909993
TI  - Detection of the gene responsible for silicic acid transport in chrysophycean
      algae.

PMID- 16909994
TI  - Therapeutic photobiomodulation of myocardium structure in the hypertensive SHR
      strain.

PMID- 16909995
TI  - Change in the Ca2+ response to formyl peptide in HL-60 myeloblastic leukemia
      cells after the induction of their differentiation by MP-4 myelogenic peptide.

PMID- 16909996
TI  - Comparison of the antimutagenic activities of natural and synthetic substances in
      irradiated repair-defective human cells.

PMID- 16909997
TI  - Expression of keratin 19 in a culture of human epidermal keratinocytes.

PMID- 16909998
TI  - Surgery for peritoneal carcinomatosis from colorectal origin: techniques and
      limitations.

PMID- 16909999
TI  - Cytoreduction and HIPEC for peritoneal carcinomatosis from colorectal origin: the
      Amsterdam experience.

PMID- 16910000
TI  - Peritoneal carcinomatosis in digestive cancers: cytoreductive surgery combined
      with intraperitoneal chemohyperthermia. The experience in Centre Hospitalier et
      Universitaire Lyon Sud (CHLS).
AB  - Intraperitoneal chemohyperthermia (IPCH) with Cytoreductive surgery (CS) has been
      used in Centre Hospitalier et Universitaire Lyon Sud (CHLS) since 1989. Up to
      2005, 420 patients were involved in different phase II studies for peritoneal
      carcinomatosis (PC) from colorectal, gastric or ovarian origin, as well as for
      pseudomyxoma peritonei and peritoneal mesothelioma. Encouraging results were
      achieved in case of optimal PC cytoreduction. The CHLS experience, as well as the
      Dutch randomized trial and the international registration, underline the
      advantage of such an aggressive combined therapy for selected patients in
      experienced multidisciplinary centers.

PMID- 16910001
TI  - Hyperthermic intraperitoneal chemotherapy in the treatment of peritoneal
      carcinomatosis of digestive and peritoneal origin: rationale.
AB  - Up to a few years ago peritoneal carcinomatosis was considered as an "incurable"
      disease. The aim of this paper is to review the surgical approach with curative
      intent to carcinomatosis: it consists of complete resection of macroscopic
      disease (R1), associated with hyperthermic intraperitoneal chemotherapy (HIPEC)
      to treat residual microscopic disease, and to evaluate its indications. Overall 5
      year survival of patients with peritoneal carcinomatosis treated by HIPEC is
      similar to that of patients with hepatic metastases treated with curative intent.
      Those patients should no longer be considered as patients with a terminal disease
      but as patients with a potentially treatable localized disease.

PMID- 16910002
TI  - Adjuvant hyperthermic intraperitoneal peroperative chemotherapy (HIPEC)
      associated with curative surgery for locally advanced gastric carcinoma. An
      initial experience.
AB  - AIM OF THE STUDY: After macroscopic radical (R0) surgery for advanced gastric
      carcinoma, 40 to 50% of the tumors recur in the abdomen as locoregional or
      peritoneal disease. We initiated a protocol in which patients with suspicion of
      macroscopic serosal, lymphatic or peritoneal invasion, treated with R0 resection,
      underwent adjuvant HIPEC. METHODS: Between June 1998 and January 2003, 16
      patients with locally advanced adenocarcinoma of the stomach were included in the
      study. Surgery consisted of a total gastrectomy with a D2 lymphadenectomy.
      Splenectomy (n = 1), splenopancreatectomy (n = 4), transverse colectomy (n = 3),
      left hepatectomy (n = 1), localized peritonectomy (n = 3) were associated to
      obtain a R0 resection. HIPEC protocol consisted of heated (42.5 degrees C)
      intraperitoneal mitomycin C (15 mg/m2) for a planned duration of 90 minutes.
      RESULTS: HIPEC median duration was limited to 73(20-90) min because of central
      hyperthermia recognition in half of the cases. One patient died in the
      postoperative period of sepsis secondary to a duodenal fistula. Postoperative
      morbidity included pancreatic fistula (n = 2), pulmonary oedema (n = 1),
      pulmonary embolus (n = 1) and transient renal failure (n = 1). UICC staging was
      IB (n = 2), II (n = 2), IIIA (n = 5), IIIB (n = 1), IV (n = 6). Nine of the 16
      patients are alive without recurrence with a median follow-up of 52 months. Four
      patients developed a recurrence, intraperitoneal (n = 2), systemic (n = 1), or
      combined (n = 1). Two patients were lost to follow-up. CONCLUSIONS: Aggressive
      surgical therapy and HIPEC might represent the standard of care in a selected
      population with locoregional disease and for whom a R0 resection can be achieved.
      This protocol was associated in this study with a 75% 5-year survival with a low
      peritoneal recurrence rate and an acceptable morbidity.

PMID- 16910003
TI  - Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for
      colorectal peritoneal carcinomatosis: higher complication rate for oxaliplatin
      compared to Mitomycin C.
AB  - BACKGROUND: Peritoneal carcinomatosis (PC) from colo-rectal cancer carries a very
      poor prognosis with a mean and median overall survival times of 6.9 and 5.2
      months. It has been proved that a locoregional therapeutic approach of this
      disease with cytoreduction followed by hyperthermic intraperitoneal chemotherapy
      (HIPEC) improved survival of these patients. However, this combined treatment
      presents a high complication rate. METHODS: 21 patients with PC of colorectal
      origin underwent complete cytoreduction followed by HIPEC using Mitomycin-C (13
      patients) or oxaliplatin (8 patients) and the open coliseum technique. For each
      case the medical datas were retrospectively analysed to determine feasibility,
      morbidity, mortality, survival time and prognostic factors. RESULTS: All patients
      presented a Sugarbaker's Peritoneal Cancer index inferior to 15. The mean
      operating time was 453 minutes. After a median follow-up of 24.9 months,
      actuarial disease-free survival was 36.6% at 5 years. The median survival time
      was 34 months. The morbidity rate was 33.3% with a significant higher
      complication rate in the oxaliplatin group (5/8) than in the Mytomycin-C (MMC)
      group (2/13). One patient (4.7%) died two months after treatment with MMC
      (endocarditis). CONCLUSIONS: This series confirm positive impact of cytoreduction
      and HIPEC on PC. We obtained a moderated complications rate thanks to a high
      degree of selection of the patient. Oxaliplatin scheme is responsible of a higher
      morbidity than in MMC group. Phase III trial comparing these two drugs is needed.

PMID- 16910004
TI  - Thoracic aortic aneurysms.
AB  - Remarkable progress has been made in the surgical treatment of thoracoabdominal
      aortic aneurysms. The decline in mortality and complication rates can be
      attributed to improvements in perioperative care and in surgical technique,
      particularly the adoption of adjunct distal aortic perfusion and cerebrospinal
      fluid drainage. Neurologic deficit is no longer a major threat to patients, as
      the use of adjuncts has brought the incidence down to 2.4% for all
      thoracoabdominal aortic aneurysms. However, we continue to pursue research to
      improve organ preservation, particularly for the most troublesome extent II
      thoracoabdominal aortic aneurysm.

PMID- 16910005
TI  - Fenestrated and branched stent-grafting: a 5-years experience.
AB  - Fenestrated stent-grafts aim at treating short-necked aneurysms. As a result of
      customized fenestrations, patency of vital side branches such as the renal
      arteries and the superior mesenteric artery can be maintained, whilst positioning
      the graft over these aortic side branches. Over the years, the technique has been
      refined. Results in a few experienced centers are good, with excellent patency
      rates of targeted side branches. Suprarenal and thoraco-abdominal aneurysms can
      only be treated by endovascular means with branched grafts. This can be achieved
      with fenestrated grafts, but with the use of covered stents through the
      fenestrations, or by fully branched grafts. Both options are feasible and present
      with specific advantages and disadvantages. This report gives an overview of our
      5-years experience with fenestrated and branched grafts, and discusses the
      following aspects of the technique: indications, technical principles, results,
      and limitations.

PMID- 16910006
TI  - Endovascular treatment of thoracic aortic pathology: lessons learned.
AB  - INTRODUCTION: Endovascular repair has emerged as a very important treatment
      modality in the management of thoracic aortic diseases due to its reduced
      invasiveness especially in patients at increased risk for open surgery. Aim of
      this study is to analyze the lessons learned in our experience of thoracic aortic
      endografting. MATERIAL AND METHODS: From June 1999 to January 2006, 145 selected
      patients (121 men and 24 women with a mean age of 70 +/- 9 years) with thoracic
      aorta disease received endovascular treatment with one of four different
      commercially produced stent grafts (Cook, Gore, Endomed, Medtronic). Indications
      for treatment included disease of the descending thoracic aorta in 92 cases, of
      the aortic arch in 43 cases and of the thoracoabdominal aorta in 10 cases. In 48
      patients, an hybrid surgical and endovascular approach was required. RESULTS:
      Primary technical success was achieved in 137/145 (94.5%) cases. One patient died
      intraoperatively and seven patients had a type "I a" endoleak. In-hospital
      complications included perioperative stroke in three patients, acute renal
      failure in two patients, acute respiratory failure in one. Initial clinical
      success was obtained in 128/145 patients (88.3%) with a mortality rate of 9/145
      (6.2%). At 38 +/- 16 months, mid-term clinical success was obtained in 89.5% of
      the followed patients. Two patients died from fatal aneurysm rupture. One type I
      endoleak was successfully treated with a rescue endovascular procedure, four
      cases of type I endoleak resolved completely without any further intervention, no
      new onset endoleak was discovered. One patient underwent a successful open
      conversion. Aneurysm expansion was observed in one patient. CONCLUSION:
      Endovascular surgery is changing the management of complex aortic disease.
      Synergy between endovascular and surgical procedures may provide a solution for
      many challenging clinical problems.

PMID- 16910007
TI  - Long-term outcomes and predictors of iliac angioplasty with selective stenting:
      is primary stenting necessary?
AB  - Percutaneous transluminal angioplasty (PTA) has become one of the initial
      treatment options in patients with iliac artery occlusive disease. Stents have
      been recommended to correct procedural complications and improve long-term
      patency. Many series advocate routine stent placement after an otherwise
      uncomplicated PTA (primary stenting) in an attempt to prevent recurrent disease.
      Currently, many physicians in the United States seem to use stents in the iliac
      artery more liberally, even on a routine basis. There is little evidence to
      support this practice, however. It is still unclear whether a stent should be
      inserted primarily or selectively. This article provides the data from an 11-year
      experience of angioplasty with selective stenting for iliac artery occlusive
      lesions and reviews the current literatures on the iliac artery stent placement.

PMID- 16910008
TI  - Abdominal aortic aneurysm repair in patients with end stage renal disease.
AB  - OBJECTIVE: Abdominal aortic aneurysm (AAA) in patients with end stage renal
      disease (ESRD) represents a challenging therapeutic problem. This study was
      undertaken to analyze the surgical outcome of AAA repair in patients with ESRD
      and discuss the optimal peri-operative management of problems that resulted.
      METHODS: Between January 1995 and January 2005, 11 patients with ESRD underwent
      abdominal aortic aneurysm repair. All patients were under chronic haemodialysis.
      Risk factors related to surgical morbidity were evaluated. RESULTS: The average
      age was 68 years (57-84 years). Nine patients were men: 8 were hypertensive, 6
      had diabetes, 4 had coronary artery disease, 3 had suffered a previous stroke, 3
      had prior myocardial infarct and 8 were smokers. The duration of haemodialysis
      was 19 months (range 2 to 46 months). Five of the 11 patients had bilateral
      common iliac aneurysms in addition to the abdominal aortic aneurysm. The average
      diameter of infrarenal AAA was 6 cm (4.8-7.5). The mean duration of operation was
      191 min. All patients underwent haemodialysis on the day before operation with an
      average period of 8.5 hours (6-12) and 2 to 20 hours postoperatively. The mean
      follow-up was 11.5 months (range 1 to 93 months). None of the patients died
      during the 30-day postoperative period. Two patients died from heart failure 3
      and 7 months later. CONCLUSION: Abdominal aortic aneurysm can be repaired in
      patients with end stage renal disease with good results, despite the increased
      morbidity and mortality of this population.

PMID- 16910009
TI  - Duodenal ulcer perforation and pneumothorax: a case report.
AB  - Pneumothorax and pneumomediastinum are rarely observed as a complication of
      perforated peptic ulcer, which is a common cause of acute abdomen. We report a
      case of a 30-year-old male patient with abdominal pain and respiratory distress.
      Resulting from physical examination and laboratory data of the patient, acute
      abdomen and pneumothorax were diagnosed simultaneously. Laparotomy revealed
      duodenal ulcer perforation and a simple patch closure was performed. No
      complications were observed during the postoperative course of the patient.

PMID- 16910010
TI  - Laparoscopically assisted subtotal colectomy for idiopathic pneumatosis cystoides
      intestinalis.
AB  - Pneumatosis cystoides intestinalis (PCI) is a rare entity in which gas filled
      cysts are found within the intestinal wall. Conservative management and the
      treatment of underlying illnesses are recommended in most patients and surgery is
      usually indicated when acute and life-threatening complications such as bowel
      necrosis, perforation or peritonitis appear. The authors report a case of
      idiopathic pneumatosis cystoides intestinalis which, after repeated failure of
      conservative treatment including the oxygen therapy in hyperbaric chamber, was
      successfully treated by laparoscopic subtotal colectomy. A laparoscopically
      assisted approach proved to be a good indication in subtotal colectomy in cases
      of PCI that are non-responsive to standard conservative treatment.

PMID- 16910011
TI  - Giant aneurysm of the splenic artery adherent to the pancreas with splenic
      infarct: report of a case.
AB  - Giant aneurysms of the splenic artery are extremely rare clinical entities. The
      size of splenic aneurysms rarely exceeds 3 cm. The treatment includes surgical
      procedures that sometimes require pancreatectomy. We present a case of a 9 cm
      giant splenic artery aneurysm tightly adherent to the pancreas which was treated
      surgically.

PMID- 16910012
TI  - Abdominal actinomycosis: a report of two cases.
AB  - Actinomyces spp. cause a chronic suppurative, granulomatous disease which is
      characterized clinically by extensive abscess formation, recurrent draining of
      sinuses and fistulae and histologically by the presence of the so-called "sulphur
      granules". Colonic actinomycosis is a relatively rare infection and its diagnosis
      is difficult. We report the case of a female patient who was operated on for
      ovarian cyst and the case of another female patient operated on for a mass in the
      transverse colon. In both cases the pathology of the excised tissues revealed
      actinomycosis. Actinomycosis must be considered in the differential diagnosis of
      patients who present with abdominal pain, fever, leucocytosis and intestinal wall
      thickness and/or abdominal mass.

PMID- 16910013
TI  - The varying morphology and aetiology of the arterial aneurysm. A historical
      review.

PMID- 16910014
TI  - London PCTs expect to spend a sixth of Choosing Health cash.

PMID- 16910015
TI  - Unions unite to oppose reform pace.

PMID- 16910016
TI  - MPs find no evidence of improved value from ITCs.

PMID- 16910017
TI  - Signs of the times: will people power deliver accountability?

PMID- 16910018
TI  - Asks questions on SHA roles.

PMID- 16910019
TI  - 'Managers are wrongly maligned'. Interview by Laura Donnelly.

PMID- 16910020
TI  - Barometer. Mental health July 2006.

PMID- 16910021
TI  - Live and direct--how five got ahead.

PMID- 16910022
TI  - Parkinson's disease. Critical diagnosis.
AB  - NICE guidance recommends that suspected Parkinson's patients are referred to a
      specialist for diagnosis. More GPs should be encouraged to refer rather than
      treat patients so they will be treated quickly, and their medicines managed by an
      expert. Nurse specialists can also be used to run clinics, freeing up consultants
      to see more new patients.

PMID- 16910023
TI  - Parkinson's disease. The power of self control.

PMID- 16910024
TI  - The MORE trial: relevance to everyday dermatology practices.

PMID- 16910025
TI  - The results of the MORE trial: overview.
AB  - Successful treatment of acne requires knowledge of the performance capabilities
      of available treatments and patient expectations. The Measuring Acne Outcomes in
      a Real-World Experience (MORE) trial was a prospective, open-label, multicenter,
      observational, phase 4 study of the effectiveness and safety of adapalene gel
      0.1% when used with other acne treatments, either as part of an initial
      combination regimen or as add-on therapy. The MORE trial also surveyed subjects
      regarding their satisfaction with treatment and their rating of adapalene gel
      0.1% versus acne treatments they had previously used. Enrollment consisted of
      1979 subjects aged 12 years or older; 1662 subjects completed the week 12
      assessment, using adapalene gel 0.1% once daily for 12 weeks according to
      protocol. Significant reductions in the number of acne lesions were seen as early
      as week 6 and were even more pronounced by week 12 (P <. 001 vs baseline for all
      lesion types at both weeks 6 and 12). Adverse events were uncommon (5.8% of
      subjects) and were generally mild, with the most common being skin or
      subcutaneous tissue disorders. Adherence to therapy was high for both the initial
      combination and add-on therapies. Subjects expressed a high degree of
      satisfaction with and preference for adapalene gel 0.1% over previous treatments.
      The MORE trial corroborates the general consensus regarding the efficacy of
      combination therapy including a topical retinoid and demonstrates that adapalene
      gel 0.1% is effective, well tolerated, and likely to enhance adherence to
      treatment.

PMID- 16910026
TI  - The MORE trial: effectiveness of adapalene gel 0.1% in real-world dermatology
      practices.
AB  - Effective treatment of acne often involves combination therapy. Topical retinoids
      are effective when used in combination with topical and/or oral antibiotics, and
      recent guidelines from the Global Alliance to Improve Outcomes in Acne recommend
      retinoids as part of initial and maintenance therapies. The Measuring Acne
      Outcomes in a Real-World Experience (MORE) trial evaluated the effectiveness,
      tolerability, and acceptability of adapalene gel 0.1% in combination with other
      acne treatments for subjects with moderate to moderately severe acne, either as
      an initial combination regimen for subjects not treated at baseline or as add-on
      therapy for patients already treated for acne. Of 1979 subjects aged 12 years or
      older who were enrolled, 1662 completed the 12-week assessment using adapalene
      gel 0.1% once daily for 12 weeks according to protocol. Adherence to therapy was
      high for both the initial combination and add-on therapies with adapalene gel
      0.1%. Significant reductions in acne lesions were seen as early as week 6 and
      were even more pronounced by week 12 (P < .001 vs baseline for all lesion types
      at both weeks 6 and 12). A majority of investigators rated adapalene gel 0.1%
      superior to other acne treatments they had prescribed, and the success rate also
      was high based on the Investigator Global Assessment. The MORE trial confirms
      that adapalene gel 0.1% is effective in clearing both inflammatory and
      noninflammatory acne lesions in patients with moderate to moderately severe acne.

PMID- 16910027
TI  - Safety and tolerability in the MORE trial.
AB  - Adverse events and a high potential for cutaneous irritation may have a negative
      effect on patient adherence to acne treatments, the primary factor contributing
      to optimal outcomes. In addition to effectiveness and subject satisfaction, the
      Measuring Acne Outcomes in a Real-World Experience (MORE) trial evaluated adverse
      events and cutaneous tolerability of adapalene gel 0.1% in 1396 subjects who
      received initial combination therapy with adapalene gel 0.1% and 468 subjects who
      added adapalene gel 0.1% to their existing regimen (safety population). Adverse
      events were uncommon (reported by 5.8% of subjects) and generally mild, the most
      frequent being skin and subcutaneous tissue disorders (2.7%). Overall,
      investigators rated cutaneous tolerability as high. Adherence to therapy also was
      high with both the initial combination and add-on therapies. The MORE trial
      confirms that adapalene gel 0.1% is safe and well tolerated and therefore likely
      to enhance adherence to treatment and the likelihood of optimal treatment
      outcomes for patients with moderate to moderately severe acne.

PMID- 16910028
TI  - Subject preferences for acne treatments containing adapalene gel 0.1%: results of
      the MORE trial.
AB  - Acne vulgaris can affect adolescents at a time of profound physical, social, and
      psychological change. The negative impact of acne on self-image and self
      confidence can be severe, leading to potential psychiatric problems and limiting
      social interactions, even in adults. Adherence is necessary for successful
      treatment of acne, and patient satisfaction is crucial for adherence. The
      Measuring Acne Outcomes in a Real-World Experience (MORE) trial enrolled 1979
      subjects who used combination acne treatments, all containing adapalene gel 0.1%.
      Among other measures, subjects were surveyed regarding their satisfaction with
      treatment. Adherence to treatment protocol was high throughout the study (94.5%
      and 88.0% at weeks 6 and 12, respectively, determined by self-report, and 93.7%
      and 80.3%, respectively, determined by filled prescriptions). Of the subjects who
      completed preference surveys, more than 70% rated adapalene gel 0.1% as much
      superior or superior to other acne treatments; more than 85% of subjects were
      very satisfied or satisfied with adapalene gel 0.1% to treat their acne; and more
      than 85% of subjects reported feeling more confident or positive after using this
      treatment. About 75% of subjects planned to continue using adapalene gel 0.1%
      and/or use it in the future if they needed acne treatment, and close to 75% of
      subjects indicated that they would recommend this treatment to a friend. The high
      level of patient satisfaction with adapalene gel 0.1% as an acne treatment is
      likely to translate into a high level of adherence to treatment, including
      maintenance treatment, and a major improvement in quality of life (QOL) for
      patients with acne.

PMID- 16910029
TI  - The effect of a daily facial cleanser for normal to oily skin on the skin barrier
      of subjects with acne.
AB  - Acne vulgaris is a common skin disorder that affects many people every year,
      especially the teenaged population. People with acne find the condition
      especially difficult to manage because of the disease's chronicity and
      variability in response to treatment. Acne is the result of pores clogged with
      shed skin cells combined with sebum in the hair follicle. Successful treatment of
      acne is important because acne has the potential to result in lasting physical
      and emotional scarring. For many years, physicians have agreed that although
      cleansing is not effective on its own, effective cleansing is an important part
      of any acne treatment regimen. However, patients have not been satisfied with the
      types of cleansers available. In addition to containing dyes and perfumes that
      can irritate and exacerbate acne, these cleansers often are too harsh and can
      result in excessive drying of the skin, which leads to overcompensation by the
      oil glands and ultimately to more oil on the surface of the skin. This study
      examined the use of a daily facial cleanser formulated for normal to oily skin in
      subjects with mild facial acne. The cleanser was studied for 2 weeks in the
      absence of additional treatments to eliminate the confounding effects of various
      treatments. Subjects were monitored for skin barrier function through
      transepidermal water loss (TEWL) and corneometry, sebum level, and lesion counts.
      The results of the study indicate that the facial cleanser is gentle and does not
      damage the skin barrier or result in sebum overcompensation; additionally, the
      cleanser is effective at deep-pore cleansing, which may help to manage some acne
      associated symptoms.

PMID- 16910030
TI  - Of mules and weaving: thinking internationally.

PMID- 16910031
TI  - Celebrating international nursing partnerships.

PMID- 16910032
TI  - A means to an end, an end in itself.

PMID- 16910033
TI  - Youth interns in Ethiopia.

PMID- 16910034
TI  - Listening to different voices.
AB  - Grounded theory research provides the foundation for this case analy sis about
      listening to the voices of refugee immigrant women in order to improve access to
      health care. The authors share the case study of "Elena" (pseudonym), a Latin
      American refugee immigrant to Canada, and explore listening as an individual and
      collective intervention. The feeling of being degraded, ignored or dismissed by
      others has serious consequences for refugee immigrants to Canada. The authors
      recommend a social advocacy approach with both individual and collective
      strategies for responding to the lack of cultural sensitivity and genuine
      listening evidenced by Elena's case. Inclusive and partnership approaches, an
      "inequities imagination" and relational approaches to difference are required to
      loosen our thinking about what shapes refugee immigrant health. A critical
      cultural perspective asks that practitioners not only listen for history and
      context in individual practice, but also take those discoveries further to change
      policy and practice systemically.

PMID- 16910035
TI  - Volunteering in Cambodia.
AB  - In August 2004, three undergraduate nursing students from the University of
      Toronto's faculty of nursing travelled to Cambodia to volunteer as student
      nurses. Being immersed in another culture helped to develop the students'
      cultural competence, enhance their understanding of primary health care and
      strengthen clinical skills. Given the growing cultural diversity in Canada,
      developing s kills in these areas is particularly important. In this article, the
      author reflects on her experiences in Cambodia and explores the unique value that
      international placements offer.

PMID- 16910036
TI  - Sowing the seeds for good health.

PMID- 16910037
TI  - Headspace-solid-phase microextraction fast GC in combination with principal
      component analysis as a tool to classify different chemotypes of chamomile flower
      heads (Matricaria recutita l.).
AB  - Headspace-solid-phase microextraction gas chromatography-principal component
      analysis (HS-SPME GC-PCA) is proposed as a complementary or alternative method to
      essential oil (EO) GC-PCA in order to discriminate between flower-heads of
      chamomile of different chemotypes. Ninety-two EOs and the headspaces sampled by
      HS-SPME of the corresponding chamomile flower-heads were examined by conventional
      GC and fast GC (F-GC) and the results submitted to statistical analysis by PCA.
      HS-SPME F-GC-PCA showed itself to be a rapid technique by which to distinguish
      chamomile flower-head chemotypes a produced results in agreement with the
      accepted EO classification. Using this method, the analysis time was reduced from
      at least 4.5 h with EO conventional GC to less than 1 h with HS-SPME F-GC. This
      approach can thus successfully be used as an analytical decision maker in order
      to reduce the number of time-consuming EO conventional GC analyses by limiting
      them to those samples that cannot unequivocally be classified. The EO
      conventional GC and HS-SPME F-GC results of PCA were very uniform, but they did
      not provide quantitative correlations between the components as determined by the
      two methods. A different statistical approach and a larger number of samples will
      be needed in order to correlate components in the headspace sampled by SPME and
      those in the corresponding EO quantitatively through a function.

PMID- 16910038
TI  - The bioactivity-guided isolation and structural identification of toxic
      cucurbitacin steroidal glucosides from stemodia kingii.
AB  - A histologically validated murine model for the ovine intoxication by Stemodia
      kingii was used as a bioassay to guide the isolation of several groups of toxins
      from Stemodia kingiL Two of the toxins from one group were purified sufficiently
      to allow structural analysis and a determination of their median lethal doses
      (LD50) for oral administration to mice. A combination of acid hydrolysis,
      elemental analysis, HPLC-MS, 1D-NMR (1H, 13C) and 2D-NMR (1H-1H COSY, 13C-1H HSQC
      and HMBC, and gNOESY) was used to define stemodiosides B3 and B4 as cucurbitacin
      steroidal glucosides. Thus stemodioside B3 is (24Z)-3 alpha-(beta
      glucopyranosyloxy)-2 beta,20,27-trihydroxy- 19-(10 -9 beta)-abeo-10alpha-lanost
      5,24-diene- 11-one and stemodioside B4 is (23E)-3 alpha-(beta-glucopyranosyloxy)
      20,20,22,27-tetrahydroxy- 19-( 10-9 beta)-abeo- 10 alpha-lanost-5,23-diene- 11
      one. The approximate oral LD50s for stemodiosides B3 and B4 in mice were
      estimated to be 99 and 42 mg/kg body weight, respectively.

PMID- 16910039
TI  - Analysis of secondary metabolites from eschscholtzia californica by high
      performance liquid chromatography.
AB  - A rapid and precise analytical HPLC method has been developed for screening the
      major benzophenanthridine alkaloids produced by cell cultures of Eschscholtzia
      califomica, namely, sanguinarine, chelirubine, macarpine, chelerythrine and
      chelilutine. Separation was achieved on a C18, reversed-phase column with
      gradient elution using acetonitrile and 50 mM phosphoric acid. Detection was
      performed by both fluorescence (lambda(ex) 330 nm, lambda(em) 570 nm) and
      photodiode array, leading to good selectivity and precision in determining peak
      purity. A simple and quick sample preparation protocol was elaborated involving a
      methanolic extraction for the measurement of intracellular concentrations of the
      alkaloids and a solid phase extraction for their quantification in culture
      medium. Owing to the non-availability of commercially standards, a method for the
      purification of chelirubine, macar pine and chelilutine by semi-preparative HPLC
      was developed. Coupled together, the isolation method and the analytical method
      were highly reliable for screening the alkaloids of interest produced by E.
      califomica.

PMID- 16910040
TI  - Isolation and characterisation of selected germander diterpenoids from
      authenticated Teucrium chamaedrys and T. canadense by HPLC, HPLC-mS and NMR.
AB  - Teucrium species, such as germander, are rich in neo-clerodane diterpenoids and
      have been used in traditional folk medicine for their stimulant, diuretic,
      antipyretic and antiseptic properties. However, the furano neo-clerodane
      diterpenoids present in germander have been implicated in the in vivo
      hepatotoxicity of this botanical. In this study, authenticated germander
      (Teucrium chamaedrys L. and Teucrium canadense L.) was used as the source
      material. Methanol extracts of powdered plant mate rial were prepared and
      analysed by HPLC using Synergi Max-RP columns with monitoring at 220 nm. Limited
      amounts of teucrin A and other diterpenoid standards were analysed on a Synergi
      Max-RP column in order to determine their retention times and to generate
      calibration curves. The same standards were subjected to concurrent mass spectral
      analysis. Teucrin A and diterpenoids such as dihydroteugin, teuflin, teuflidin
      and teucvidin were tentatively identified in the plant extracts by HPLC-MS and 1H
      NMR experiments. For the isolation of teucrium diterpenoids on a semipreparative
      scale, a solid-phase extraction method was developed for the first time using
      styrene divinylbenzene and strata-X sorbents for teucrin A and teuflin,
      respectively. Semi-preparative HPLC of the methanol extract of the powdered
      aerial parts of Teucrium plants was carried out on a semipreparative Synergi Max
      RP column with photodiode array detection in order to confirm the identities of
      some diterpenoids by HPLC-MS and NMR.

PMID- 16910041
TI  - RP-HPLC detection of a sulphiting-induced artefact from paeoniflorin in dried
      roots of Paeonia lactiflora.
AB  - Paeoniflorin is one of the bioactive ingredients of the roots of Paeonia
      lactiflora (Paeoniaceae). A comparative study of processed and non-processed
      commercial samples of dried roots of P. lactiflora indicated a very low level of
      paeoniflorin in the processed sample and the formation of a new more polar
      component, sodium paeoniflorin sulphonate, during treatment of the roots with
      sulphiting agents.

PMID- 16910042
TI  - Determination of catalase-like activity in plants based on the amperometric
      monitoring of hydrogen peroxide consumption using a carbon paste electrode
      modified with ruthenium(IV) Oxide.
AB  - A carbon paste electrode containing ruthenium(IV) oxide as a modifier was tested
      as an effective hydrogen peroxide amperometric sensor in bulk measurements
      (hydrodynamic amperometry). Factors that influence its overall analytical perform
      ance, such as pH and the applied potential, were examined. The RuO2-modified
      electrode displayed high sensitivity towards hydrogen peroxide, with detection
      limits as low as 0.02 mm at pH 7.4 and 0.007 mM at pH 9.0. The method was applied
      for monitoring the decomposition of hydrogen peroxide (by catalase) in phosphate
      buffer of pH 7.4. The relative response of the electrode towards ascorbic acid
      was assessed and it was found that the selectivity of the RuO2-modified electrode
      towards hydrogen peroxide over ascorbic acid could be significantly improved by
      electro-polymerizing m-phenylenediamine on its surface prior to measurements. The
      RuO2-modified electrode was used for the kinetic (fixed time) determination of
      catalase activity in the range of 4-40 U/mL (detection limit 1.2 U/mL). The
      method was applied to the determination of catalase-like activity in various
      plant materials (recov-ery ranged from 93 to 101%, detection limit 480 U/100 g).

PMID- 16910043
TI  - Development of a protocol for the semi-synthesis and purification of
      betaxanthins.
AB  - A method for the analytical and semi-preparative chromatographic purification of
      betaxanthins is described together with an improved procedure for the semi
      synthesis of these compounds from betalamic acid. Standard conditions for
      obtaining preparative amounts of betaxanthins free of the precursor amino acids
      are provided. Following this procedure, 14 pure betaxanthins were obtained with
      yields of up to 100%. A simple reversed-phase HPLC protocol for pigment
      identification and quantification is also provided. Calibration for betaxanthins
      is reported for the first time using the synthesised and purified pigments as
      standards. Structures were confirmed by UV-vis spectroscopy, HPLC retention times
      and electrospray ionization mass spectrometry. Betaxanthins can be obtained pure,
      and in sufficient amounts for further studies, which opens up new perspectives in
      the research and applications of these pigments.

PMID- 16910044
TI  - Exercise responses following heart transplantation: 5 year follow-up.
AB  - Heart transplantation is an established treatment for end stage heart failure. In
      addition to increased life expectancy, heart transplant recipients report a
      remarkable improvement in symptoms and functional capacity. Exercise performance
      following heart transplantation, however, remains impaired even in the absence of
      exertional symptoms. We have assessed the response to exercise in 47 patients
      with cardiac failure prior to and then at yearly intervals to five years post
      transplantation. All patients performed incremental symptom limited exercise
      tests during which minute ventilation (V'E), oxygen consumption (V'O2) and carbon
      dioxide production (V'CO2) and heart rate (HR) were measured. Ventilatory
      response (V'E/V'CO2), anaerobic threshold (V'O2 AT %predicted) and heart rate
      response (HR/VO2) were calculated. The dead space to tidal volume ratio (VD/VT)
      and alveolar-arterial oxygen gradient (A-aO2) were computed from transcutaneous
      monitoring. Despite substantial improvement in subjective functional capacity,
      heart transplant recipients continue to have limited exercise performance
      [Maximal V'O2% predicted pre-transplant 41.3 (2.2); 1 year 48.6 (1.7), p <0.001:
      V'O2 AT% 31.5 (1.1); 1 year 35.6 (1.0); respectively p<0.05]. The maximal oxygen
      uptake continued to improve at two years post-transplant but, thereafter, there
      was no further significant change at up to 5 years post transplant [50.9 (1.5)].
      At one year post-transplantation peak HR [65.2 (0.9) vs 79.1(1.4)] and the HR/VO2
      response [24.0(1.8) vs 79.6(4.2)] were significantly reduced compared to pre
      transplant values. The heart rate response remained lower compared to predicted
      at 5 years post-transplant although there was a significant increase compared to
      one year post-transplant (32.9 vs 24.0mls/bt). There was a weak but significant
      relationship between maximal VO2 and peak HR (0.39, p<0.05) and HR/VO2 (r= 0.37,
      p<0.05) at one year post-transplant. Prior to transplantation the ventilatory
      response to exercise was elevated [V'E/V'CO2 45.6 (2.5)] and decreased
      significantly following transplantation [1 yr 34.1 (1.3), respectively p<0.001].
      In addition, despite significant improvement in VD/VT after transplantation, it
      remained higher than normal [Pre VD/VT at maximum exercise 0.35 (0.02); 1 yr 0.31
      (0.02); p<0.05]. There was a further fall in the VE/VCO2 and VD/VT at two years
      post-transplantation with no further change at up to 5 years post transplantation
      [VE/VCO2 32.0 (1.0); VD/VT 0.29 (0.01)]. Although cardiac output is markedly
      improved after transplantation, due to chronotropic incompetence associated with
      denervation, its response remains subnormal and this may explain the residual
      abnormalities of ventilatory and gas exchange responses to exercise following
      transplantation.

PMID- 16910045
TI  - Alexithymia in diabetes mellitus.
AB  - BACKGROUND: Diabetes mellitus is a chronic, progressive disease with complex
      therapy protocols requiring major coping efforts from patients to achieve and
      maintain glycaemic control in order to reduce risk of diabetic complications.
      Disease coping strategies including good knowledge of diabetes and high ability
      of self-care have been reported to be impaired by alexithymic features.
      Alexithymia is a psychological construct characterised by inability to express
      emotions verbally, poor imagination and operational thinking, leading to failure
      in psychological self-regulation. OBJECTIVE: To compare prevalence of alexithymia
      and mean Toronto Alexithymia Scale-26 (TAS-26) scores in diabetic patients with
      non-diabetic controls; to investigate the association of alexithymia with
      glycemic control in diabetes. METHOD: In this cross- sectional study, TAS-26
      scores of 193 diabetic patients and 49 non-diabetic controls were compared.
      Disease related factors were obtained from patient records. Alexithymia was used
      as a continuous (mean TAS-26 scores) and semi-quantitative (dichotomised into non
      alexithymic 11>TAS-26 scores>11 and alexithymic individuals) variable.
      Descriptive data are presented as mean +/- SD, median (range) or %. Differences
      in means were compared via Independent-Samples T Test and One-Way ANOVA.
      Proportions were analysed with chi-square test and odds ratios (OR) were
      calculated via cross tabulation with a confidence interval (CI) of 95%. P<0.05
      was considered statistically significant. RESULTS: The control group was similar
      with respect to age, gender and education with the diabetic group. In the
      diabetic study population (n=193, male/female: 42/58%, age 54.2 +/- 14.0 years,
      median diabetes duration 7 years (1-32 years), postprandial blood glucose (PBG)
      243 +/- 110 mg/dl HbA1 c 7.3 +/- 3.6%) prevalence of alexithymia was
      significantly higher than in the control group (65 % in diabetics vs. 45 % in
      controls, p=0.011; mean TAS-26 score 12.3 +/- 3.7 vs. 10.6 +/- 3.6, p=0.004,
      respectively). Poor postprandial glycaemic control (p=0.002), female gender
      (p=0.026), combination therapy (p=0.037) and poor educational level (p=0.005)
      were positively associated with TAS-26 scores in diabetic individuals.
      Alexithymic diabetic patients were less educated (OR=1.2, p=0.046) and under
      worse glycaemic control (OR=2.4, p=0.005) compared to their non-alexithymic
      counterparts.

PMID- 16910046
TI  - Flexible trainees in Scotland.
AB  - INTRODUCTION: Demand for flexible training is increasing. The contribution of
      such trainees to the trained medical workforce is not clear. METHODS: All full
      time and flexible trainees in Scotland were 'tracked' at the completion of
      training. RESULTS: 80% of flexible trainees took up a consultant post of which
      93% were in Scotland. 82% of full time trainees took up a consultant post of
      which 80% were in Scotland. DISCUSSION: Flexible trainees become consultants at
      the same rate as their full time counterparts. They are commonly geographically
      tied and are therefore more likely to remain in Scotland and contribute to
      retention of doctors in this country.

PMID- 16910047
TI  - Negligence claims for treatment of neurological disease: cases from the Medical
      and Dental Defence Union of Scotland.
AB  - There is no detailed description of negligence claims made against clinicians
      treating neurological disease in the U.K. Here negligence claims concerning
      treatment of neurological disease, which were handled by the Medical and Dental
      Defence Union of Scotland (MDDUS), were audited. Sixty-two cases were identified;
      in 38 cases the clinician was a neurosurgeon, in 16 a neurologist and in 8 a
      General Practitioner (G.P). The most common conditions were inter-vertebral disc
      disease and neoplasia, the most common misadventure was improper performance of
      procedure and most of the cases resulted in severe permanent disability.

PMID- 16910048
TI  - Dietary and social characteristics of children with severe tooth decay.
AB  - BACKGROUND AND AIMS: Dental decay remains a major public health problem in
      Scottish children. The aim of this study was to investigate the relationship
      between diet, bowel habit, social class, and body mass index (BMI) in children
      with severe tooth decay. CHILDREN AND METHODS: A cross sectional study of 165
      children aged 3 -11 years attending Glasgow Dental Hospital for extraction of
      teeth under dental general anaesthesia (DGA), was undertaken. A structured
      questionnaire was used to obtain information from each child on diet, bowel
      habit, and social status of their parents. Fibre and sugar scores were calculated
      from the frequency of consumption of a range of relevant foods. RESULTS: The
      children (mean age 5.7 (SD1.8) years) had between 1 and 20 decayed, missing or
      filled primary teeth (dmft) with a mean dmft of 7.9 (SD 3.5). 37% ate a chocolate
      bar daily, and 29% regularly drank a sugary drink after brushing their teeth. An
      excess of children were from the most deprived parts of the city and they had the
      worst decay. Children with the worst decay were also significantly thinner. No
      relationship was found between tooth decay and bowel habit. CONCLUSIONS: In this
      selected group of children with poor dental health, those from deprived families
      were over-represented and had significantly more decay. Severe dental decay was
      also associated with underweight.

PMID- 16910049
TI  - Cost savings and quality improvement--single-use suture instruments?
AB  - AIM: To determine if the instruments found in single-use suture kits are of
      satisfactory quality when compared with re-useable instruments and to determine
      the cost implications of changing to these kits. METHODS: Audit of established
      practice, followed by trial of new suture kits and their introduction to the
      department. The new practice was then audited. A cost analysis was conducted.
      RESULTS: The audit showed numerous problems with the traditional suture kits
      (instruments were breaking or no longer suitable for suturing wounds). A trial of
      single-use instruments demonstrated them to be high quality and provided new
      instruments each time. A repeat audit at one year post-introduction demonstrated
      no identifiable problem with the new suture kits. The subjective impression of
      staff was of an improvement compared to the old kits. Costs of sterilising suture
      instruments were determined and it was found that single use suture kits were
      cost effective. Assuming an average usage of 150 kits per month, at pound 4.45
      each cost for sterilisation, and a total cost of pound 3.05 each for a single-use
      suture kit plus dressing pack per patient, this yielded a projected cost saving
      of pound 2520.00 per annum. The actual cost saving was pound 1981.00 that year.
      The shortfall was due to overestimation of average usage. CONCLUSION: Single use
      instruments would appear to be safe and cost effective in the emergency
      department setting.

PMID- 16910051
TI  - Lyon Playfair (1818-1898) and compulsory vaccination.
AB  - Lyon Playfair was born in India but brought up by his uncle in St Andrews. He
      studied medicine in Glasgow and Edinburgh but never practised as a doctor.
      Instead he worked for the chemist Thomas Graham in London and then studied for a
      PhD with Liebig in Germany. While serving on a government commission he became
      very interested in public health, particularly the control of infectious
      diseases. In 1883, while a member of parliament, he made a passionate speech in
      support of a government bill in favour of compulsory vaccination against
      smallpox. He was violently attacked for his speech in a pamphlet by William
      White, an adherent of the teachings of the Swedish mystic Emanuel Swedenborg.
      Playfair died in 1898 and is buried in St Andrews.

PMID- 16910050
TI  - 21st century stroke--A medical emergency.

PMID- 16910052
TI  - Where are Indian adult celiacs?

PMID- 16910053
TI  - Neuroendocrine tumors of the pancreas.
AB  - Pancreatic Neuroendocrine tumors (PNET) are rare tumors that require a high
      degree of suspicion for timely diagnosis. They are best divided into functional
      and nonfunctional varieties. Functional tumors often are symptom specific and are
      diagnosed at an earlier stage than nonfunctional tumors. The severity of symptoms
      and pace of disease should dictate therapy. Surgical extirpation remains the only
      curative modality for localized disease, but palliation of hormone-related
      symptoms can be achieved with different modalities (Management of hormonal
      Excess, biologic therapy, chemotherapy and biochemotherapy, local-regional
      therapy with hepatic arterial embolization).

PMID- 16910054
TI  - Peritoneal adhesions: pathogenesis, assessment and effects.
AB  - BACKGROUND: As modem surgery has evolved, there has been an increase in
      iatrogenic peritoneal adhesions. Most surgeons manage adhesions and their related
      complications on a regular basis. Studies in recent years have improved the
      understanding of the pathogenesis and impact of adhesions, which are discussed.
      METHODS: A systematic search of literature was performed to identify publications
      addressing the etiopathogenesis, clinical spectrum and effects of adhesions,
      using the following database: Medline (1966 to April 2005), Embase (1974 to April
      2005), and the Cochrane controlled trials register. The reference lists of key
      publications so identified were in addition scrutinized for additional articles
      of relevance. RESULTS: Adhesions occur in more than three fourths of patients
      following laparotomy. Perironeal trauma results in a unique inflammatory process
      in which fibrin formation and fibrinolysis play a central role. The effects of
      adhesions are unpredictable but are wide ranging, causing a significant health
      care burden. Intestinal obstruction, infertility, problems at reoperative surgery
      and cumulative costs of care over many years are the key concerns. While
      adhesiolysis is beneficial in adhesive intestinal obstruction and infertility,
      its value in chronic pain is uncertain. CONCLUSION: Every violation of the
      peritoneum carries a potentially lifelong risk of a range of complications. Data
      available on the epidemiology and natural history of adhesions call for a wider
      acknowledgement of the problem in the planning of services and greater attention
      to preventive strategies.

PMID- 16910055
TI  - Evaluation of an in-house rapid diagnostic method for detection of Salmonella
      enterica serovar Typhi in fecal specimens.
AB  - Salmonella enterica serovar Typhi is the etiological agent of typhoid fever.
      Laboratory diagnosis requires isolation and identification of the organism from
      the patient's blood or feces. Feces is the specimen most commonly submitted to
      laboratories. Detection of bacterial antigens is an important adjunct to
      laboratory diagnosis. We carried out an in-house diagnostic method by preparing
      test reagents comprising of latex beads coated with specific antisera to detect
      Vi, O9 and H-d antigens of S. typhi. Fecal specimens from one hundred patients
      with diarrhea and fever as well as from twenty healthy controls were incubated
      for enrichment in Selenite F broth for 6 hours or overnight. Latex agglutination
      tests to detect antigens of S. typhi were carried out on centrifuged broth
      supernatants. Parallel cultures on media selective for S. typhi were also set up.
      Nine of the supernatants were positive for two or more specific antigens and S.
      typhi grew in three of the corresponding cultures. None of the samples from 20
      healthy controls were positive by either the diagnostic method or by culture. The
      result of the in-house diagnostic assay can be obtained overnight and may help in
      directing immediate antimicrobial therapy.

PMID- 16910056
TI  - Estimation of endotoxin in infected bile from patients with biliary diseases.
AB  - Diseases of the biliary tract can get complicated by infection. Endotoxin may
      theoretically be responsible for damage to the gall bladder due to its numerous
      pathophysiological effects. The aim of the present study was to detect and semi
      quantitate the amount of endotoxin present in the bacteriologically positive bile
      samples and to correlate the endotoxin levels with the clinical profile of the
      patients. One hundred patients with gall bladder diseases and with infected bile
      constituted the population for investigation. The clinical profile included
      presence of fever, jaundice, abdominal pain and gall bladder stones. Endotoxin
      detection and semi-quantitation in the bile samples were carried out using the
      Limulus amoebocyte assay: Of 100 infected bile samples investigated, 9 samples
      (9%) were positive for endotoxin ranging from 1.9 EU/ml to 15 EU/ml. Four of them
      had Klebsiella pneumoniae, 2 had Acinetobacter anitratus and one each of the
      remaining 3 samples was positive for (i) Escherichia coli and Serratia marcescens
      (ii) Pseudomonas aeruginosa and (iii) Salmonella enteritidis. The stool sample of
      the patient with S. enteritidis in the bile also grew the same microorganism.
      Statistical analysis showed a significant increase in the presence ofjaundice
      (p<0.05) and abdominal pain (p<0.01) in the endotoxin positive patients compared
      to the endotoxin negative ones. Hitherto this is the first report that
      investigated the endotoxin levels in the bile of patients with gall bladder and
      biliary tract diseases, along with their biliary bacterial profile. Further
      research is warranted on the effects of endotoxin on gall stone formation.

PMID- 16910057
TI  - Garlic hepatotoxicity: safe dose of garlic.
AB  - Information on the effect of garlic on the liver and optimal dose of garlic to
      avoid liver damage is not known. This study was planned to determine the safe
      dose of garlic. Male wistar rats (110-170g) were fed fresh garlic homogenate
      (FSH) orally in three different doses (1.0, 2.5 and 5.0 g/kg body weight/day)
      daily for 28 days. Liver histology, serum transaminases, bilirubin and alkaline
      phosphatase were estimated at 0, 14, 21 and 28 days in control and experimental
      animals. 1.0, 2.5 and 5.0 g/kg body weight/day of garlic showed significant
      (P<0.001) deterioration in liver function tests (LFT's) after 21, 14 and 7 days
      respectively. A 1.0 g/kg body weight/day dose of garlic was associated with
      marked histological damage in liver after 21 days. Therefore, three lower doses
      of garlic (0.1, 0.25 and 0.5 g/kg body weight/day) were given orally to another
      group of similar rats to determine the safe dose of garlic. LFT's were serially
      measured and animals were sacrificed on the 29th day of experiment. All three
      lower doses showed significant deterioration in the LFT's values of animals after
      28 days of feeding the freshly prepared garlic homogenate. Both doses of garlic
      i.e. 0.1 and 0.25 g/kg body weight/day were associated with normal histology of
      liver, but 0.5 g/kg body weight/day dose of garlic showed morphological changes
      in the liver of one animal. Therefore, the present study suggests that garlic
      with high dose has the potential ability to induce liver damage and low doses
      (0.1 or 0.25 g / kg body weight/day) are safe doses of garlic.

PMID- 16910058
TI  - Achalasia cardia: A study of 113 patients managed with indigenous dilator.
AB  - BACKGROUND: Endoscopic dilatation of achalasia cardia is an effective nonsurgical
      management option. It requires costly pneumatic dilators which are used under
      fluoroscopic guidance. This study assesses the efficacy and safety of an
      indigenous pneumatic dilator used without fluoroscopic guidance. METHODS: Over a
      period of eleven years, 113 patients (69M, 44F) ofachalasia cardia underwent
      dilatation with indigenous pneumatic dilators without fluoroscopic guidance. The
      dilatation was performed under endoscopic vision. RESULTS: The procedure was
      successful in all patients. After six weeks following dilatation, there was
      significant improvement in the mean dysphagia score 3.63 + 0.61 to 0.53 + 0.93
      (P<0.01). The response was still significant (0.78 + 1.03, P <0.05) at the end of
      one year. Excellent response with single dilatation was seen in 70.7% patients.
      After two dilatation sessions 92% of patients showed an excellent response. One
      patient had perforation. There was no mortality. CONCLUSION: Pneumatic dilatation
      under endoscopic vision without fluoroscopic assistance with the indigenous
      dilator is very effective and safe for short term treatment of achalasia carida.

PMID- 16910059
TI  - Corrosive injuries of esophagus and stomach--issues in management.

PMID- 16910060
TI  - Intestinal ischamemia in a child due to polyarteritis nodosa: a case report.
AB  - Polyarteritis nodosa (PAN) is a rare type of childhood vasculitis. We report the
      case of a 10-year-old boy who was referred to our hospital following an
      appendicectomy with fever, abdominal pain, vomiting, diarrhoea, weight loss,
      joint pains and skin rash. Shortly after admission, he developed peritonitis, and
      an emergency laparotomy revealed ischaemia of the jejunum which required partial
      resection. Histologic examination of the resected bowel showed features
      consistent with PAN. He was treated with steroids and cyclophosphamide. Nineteen
      months later, he is asymptomatic and thriving. PAN should be included in the
      differential diagnosis if a child with constitutional symptoms also has
      gastrointestinal complaints or develops an acute abdomen.

PMID- 16910061
TI  - Intestinal amyloidosis presenting as malabsorption syndrome.
AB  - Intestinal amyloidosis presenting with small bowel diarrhoea with malabsorption
      is an infrequent clinical entity. The present case report includes such a case
      and discusses the diagnostic approach in such a case.

PMID- 16910062
TI  - Diaphragm disease of the ileum: a case report.
AB  - Non-steroidal anti-inflammatory drugs induced diaphragm like lesions are a rare
      cause of small intestinal obstruction. They occur most commonly in elderly
      patients who have been consuming these drugs for prolonged periods for pain
      relief. We report the first case of ileal diaphragm disease from Asia. She
      responded well to localised resection of the diseased ileum. Intra-operative
      enteroscopy may be helpful in deciding the extent of intestinal resection.

PMID- 16910063
TI  - Hemoperitoneum as a first manifestation of HCC with bleeding from ruptured
      aberrant vessel: a case report.
AB  - A young man presented with a history of abdominal pain and distension for 4 days.
      Diagnosis of spontaneous hemoperitoneum was made after clinical examination,
      abdominal USG and a diagnostic peritoneal tap. Emergency laparotomy revealed
      massive hemoperitoneum with extensive bilobar hepato-cellular carcinoma (HCC). A
      ruptured aberrant vessel communicating between the intercostal vessel and HCC in
      the liver had caused massive hemoperitoneum.

PMID- 16910064
TI  - Schwannoma of bile duct--a case report.
AB  - This is a case report of a 29 year old woman who presented with painless and
      progressive obstructive jaundice. Imaging investigations of the abdomen revealed
      a tumour of the common bile duct. She was treated by complete excision of the
      bile duct and hepaticojejunostomy. The histopathology report of the tumour read
      as benign schwannoma.

PMID- 16910065
TI  - Abrikosoff's tumor of the esophagus: case report and review of literature.
AB  - Abrikosoff's tumor or granular cell tumor is a neoplasm of neural origin, usually
      located in the head and neck region. A majority of these neoplasms are benign.
      Only 4-6% of granular cell tumors are located in the gastrointestinal tract. It
      is extremely unusual for these tumors to be located in the esophagus. This case
      is being reported in view of the rarity of this lesion. A brief review of
      literature with stress on diagnostic evaluation and management issues is also
      included.

PMID- 16910066
TI  - Evaluation of the role of prophylactic antibiotics in elective laparoscopic
      cholecystectomy: a prospective randomized trial.
AB  - At present the use of prophylactic antibiotics in elective laparoscopic
      cholecystectomy is controversial. This prospective study was carried out to
      define the role of prophylactic antibiotics in elective laparoscopic
      cholecystectomy to prevent postoperative infection. Ninety three patients were
      randomly placed in two groups. Group A comprised of 40 while group B consisted of
      53 patients. Patients in Group A received 1.5 grams of second generation
      cephalosporin (cefuroxime sodium) diluted in 100ml of normal saline, at the time
      of induction of anesthesia. Group B patients received an equal volume of normal
      saline only. A sample of gall bladder bile was collected by direct gall bladder
      puncture intra-operatively for aerobic and anaerobic culture. Age, sex, weight of
      the patient, American Society of Anesthesiologists classification grade, presence
      of diabetes mellitus, episodes of colic 30 days preceding surgery, intra
      operative gall bladder rupture, stone and / or bile spillage, results of bile
      culture, gall bladder histology, length of hospital stay, and number of septic
      complications were recorded and analyzed. In group A, one patient (2.5%) had post
      operative wound infection and in group B, two patients (3.8%) had post operative
      infection which was statistically similar (p>0.1). There was no difference
      between the two groups in terms of demographic, intra operative and post
      operative denominators. Therefore the study concluded that prophylactic
      antibiotics did not have a significant role to play in prevention of
      postoperative wound infection in elective laparoscopic cholecystectomy.

PMID- 16910067
TI  - Removal of self-expandable metallic wallstent--a case report.
AB  - Self-expandable metallic stents (SEMS) have become the preferred palliative
      treatment for patients with malignant biliary obstruction; endoscopic stent
      placement is less invasive than surgery and is rapidly effective. A longer
      duration of patency makes SEMS superior to plastic stents for palliation of
      patients with malignant stricture. Few cases of removal of an uncovered SEMS are
      reported in case of a blocked stent. We report the first case report of removal
      of covered biliary SEMS from India.

PMID- 16910068
TI  - [The reflection of different aspects of brain activation in the
      electroencephalogram: quantitative electroencephalography of the states of rest
      with the eyes open and closed].

PMID- 16910069
TI  - [Relationship between rapid changes in an individual subrange of the
      electroencephalogram delta wave and heart rate during sleep].

PMID- 16910070
TI  - [Characteristics of ventilatory control during exercise in coronary heart disease
      patients].

PMID- 16910071
TI  - [Possibilities of a pulsogram for estimation of the wave structure of the cardiac
      rhythm].

PMID- 16910072
TI  - [Simulation of individual risk based on the results of loading tests and analysis
      of risk factors].

PMID- 16910073
TI  - [A formalized criterion of cardiorespiratory synchronization for assessment of
      dynamic changes in autonomic homeostasis].

PMID- 16910074
TI  - [Dynamics of the integrated characteristics of heart rate variability and
      psychophysiological parameters of students under the conditions of daily and
      weekly academic loads].

PMID- 16910075
TI  - [Nervous control of respiration].

PMID- 16910076
TI  - [Comparison of responses to CO2 under the conditions of natural respiration and
      controlled artificial pulmonary ventilation].

PMID- 16910077
TI  - [Patellar reflex: II. Associated activation].

PMID- 16910078
TI  - [Adaptive reactions of the endocrine system of children living under conditions
      of contrasting photoperiods].

PMID- 16910079
TI  - [Serum levels of immunoglobulins, allergen-specific IgE antibodies, and
      interleukin-4 in cosmonaunts before and after short flights on the international
      space station].

PMID- 16910080
TI  - [Effects of chorionic gonadotropin on peripheral monocytes vary with the phases
      of the menstrual cycle].

PMID- 16910081
TI  - [Physiological burden of hyperthermia of various etiologies in humans].

PMID- 16910082
TI  - [Platelet aggregability in apparently healthy humans of different ages].

PMID- 16910083
TI  - [APUD cells. The human pulmonary neuroendocrine system].

PMID- 16910084
TI  - [Human placental myeloperoxidase in miscarriage].

PMID- 16910085
TI  - [Characteristics of interhemispheric relationships in the absence or presence of
      a skill].

PMID- 16910086
TI  - [Pupillary reactions during transcranial magnetic stimulation].

PMID- 16910087
TI  - HRDI seeks settlement. Networking group is under antitrust scrutiny.

PMID- 16910088
TI  - Controversy, salaries rise. Ranking of CEO pay at publicly traded companies shows
      that as pay rises, so does federal interest in compensation policies.
AB  - The scrutiny of executive pay is ratcheting up. More healthcare companies have
      gotten subpoenas on stock options, and the SEC is making it easier for investors
      to understand how executives are paid. The heat already has UnitedHealth easing
      some of its practices. Others may follow suit. "Most compensation policies seem
      to be driven primarily by what a company's peers are doing," says Paul Hodgson,
      left.

PMID- 16910089
TI  - Big payment changes ahead? Industry anxiously awaits CMS inpatient PPS ruling.

PMID- 16910090
TI  - House passes IT bill. Deadline set for ICD-10 implementation.

PMID- 16910091
TI  - Proceed with caution. Ore. system learns hard lesson on construction, credit.

PMID- 16910092
TI  - Added incentive. Pay packages increasingly linked to executive performance.

PMID- 16910093
TI  - Transparent motives. UPMC blazes trail for not-for-profits in Sarbanes-Oxley
      compliance.

PMID- 16910094
TI  - Paid for performance. Chief medical officers get healthy salary bump in '05.

PMID- 16910095
TI  - 20 largest health insurers, by revenue based on 2005 healthcare-related revenue
      from health, life and health statutory filings.

PMID- 16910096
TI  - The relationship between tumors and the lymphatics: what more is there to know?
AB  - Ten years ago the relationship between tumors and the lymphatic system was
      perceived to be rather passive. Since then, the dramatic increase in our
      understanding of the molecular biology of lymphatic endothelial cells and the
      regulation of lymphangiogenesis has revealed that tumors can actively interact
      with the lymphatics by inducing lymphangiogenesis. In turn, this interaction
      promotes the entry of tumor cells into the lymphatic vasculature and their
      subsequent transport to regional lymph nodes, a process that stimulates the
      formation of metastases. Tumor-induced lymphangiogenesis has thus emerged as an
      important new target in the fight against metastatic cancer. Nevertheless, there
      is still much to be learned about the relationship between tumors and the
      lymphatics that will have important ramifications for the design of clinical
      trials aimed at the application of anti-lymphangiogenesis therapies in the
      management of cancer. This Lymphangiogenesis Review focuses on these issues.

PMID- 16910097
TI  - Lymphoscintigraphy as a diagnostic tool in patients with lymphedema of filarial
      origin--an Indian study.
AB  - Lymphedema is a common clinical problem. Filariasis is the commonest cause of
      lymphedema in India and is a chronic debilitating disease. The purpose of this
      study is to highlight the role of lymphoscintigraphy in the evaluation of
      lymphedema. Our study population consisted of 418 patients diagnosed with
      filarial lymphedema of different clinical stages referred for lymphoscintigraphy
      of the limbs by the lymphologist at our institution. An analysis of the various
      studies was done to determine how lymphoscintigraphy can be useful in
      documentation of the diagnosis, evaluation, as a screening procedure to prevent
      progression, and to enhance management of filarial lymphedema.

PMID- 16910098
TI  - The absence of lymphatics in normal and atherosclerotic coronary arteries in man:
      a morphologic study.
AB  - It has been suggested by various investigators that the impairment of lymphatic
      drainage from the coronary arteries may play a role in predisposition to coronary
      atherosclerosis, the pathogenesis of which is certainly multifactorial. In our
      study, no lymphatic vessels were found in the walls of the coronary arteries
      (adventitia, media and intima) in 51 human hearts from patients ranging in ages
      from 3 months to 83 years with normal coronary arteries, coronary
      atherosclerosis, and cardiomyopathy. Visualized lymphatics were located solely in
      the periadventitial area, and these lymphatics were more irregular in hearts from
      older persons. With injection, histology, and electronmicroscopy methods we could
      not detect penetration of lymphatics into the wall of coronary trunks in normal
      as well atherosclerotic arteries. In all coronary arteries studied, and
      particularly in the atherosclerotic lesions, blood vasa vasorum could be
      visualized. In the atherosclerotic areas, vasa vasorum (angiogenesis) could be
      seen penetrating into the media and intima. Many of the thin-walled vasa vasorum
      could easily be mistaken for lymphatics. The absence of lymphatics draining the
      epicardial coronary arteries may be a predisposing factor to coronary
      atherosclerosis.

PMID- 16910099
TI  - Comparative lymphatic, ocular, and metabolic phenotypes of Foxc2
      haploinsufficient and aP2-FOXC2 transgenic mice.
AB  - FOXC2 mutations cause the lymphatic/ocular disorder Lymphedema-Distichiasis (LD),
      and Foxc2 haploinsufficient mice mimic this disorder. To determine if FOXC2
      overexpression might also cause lymphatic and/or ocular abnormalities, we
      performed dynamic lymphatic imaging (Evans blue dye), ocular tissue examination,
      and metabolic profiles in mice: transgenic for FOXC2 with an adipocyte (aP2)
      promoter (aP2-FOXC2 Tg), heterozygous for targeted disruption of Foxc2 (Foxc2+/
      ), or compound heterozygous and transgenic (Foxc2+/-, Tg) compared to wild-type
      controls (WT). Foxc2+/-; aP2-FOXC2 Tg; and Foxc2+/-, Tg, exhibited LD's
      distinctive hyperplastic lymphatic phenotype characterized by increased number of
      lymphatic channels and lymph nodes as well as retrograde lymph reflux. Foxc2+/-,
      and Foxc2+/-, Tg but not aP2-FOXC2 Tg or WT showed an abnormal ocular phenotype.
      Previously described alterations in brown/ white fat distribution and lean
      phenotype in aP2-FOXC2 transgenics were confirmed. AP2-FOXC2 Tg
      immunohistochemistry disclosed aberrant FOXC2 expression in ectopic sites,
      especially embryonic heart. Lymphatic system links with fat metabolism are
      discussed.

PMID- 16910100
TI  - Hand volume estimates based on a geometric algorithm in comparison to water
      displacement.
AB  - Assessing changes in upper extremity limb volume during lymphedema therapy is
      important for determining treatment efficacy and documenting outcomes. Although
      arm volumes may be determined by tape measure, the suitability of circumference
      measurements to estimate hand volumes is questionable because of the deviation in
      circularity of hand shape. Our aim was to develop an alternative measurement
      procedure and algorithm for routine use to estimate hand volumes. A caliper was
      used to measure hand width and depth in 33 subjects (66 hands) and volumes (VE)
      were calculated using an elliptical frustum model. Using regression analysis and
      limits of agreement (LOA), VE was compared to volumes determined by water
      displacement (VW), to volumes calculated from tape-measure determined
      circumferences (VC), and to a trapezoidal model (VT). VW and VE (mean +/- SD)
      were similar (363 +/- 98 vs. 362 +/-100 ml) and highly correlated; VE = 1.01VW 
      3.1 ml, r=0.986, p<0.001, with LOA of +/- 33.5 ml and +/- 9.9 %. In contrast, VC
      (480 +/- 138 ml) and VT (432 +/- 122 ml) significantly overestimated volume
      (p<0.0001). These results indicate that the elliptical algorithm can be a useful
      alternative to water displacement when hand volumes are needed and the water
      displacement method is contra-indicated, impractical to implement, too time
      consuming or not available.

PMID- 16910101
TI  - Psycholymphology: why not all patients with chronic lymphedema want therapy.
AB  - This Commentary provides the reader with various motivations and psychologic
      factors patients have for refusing as well as for accepting long-term therapy of
      lymphedema.

PMID- 16910102
TI  - The new guy on the block.

PMID- 16910103
TI  - Analyzing acute-chemical-release data to describe chemicals that may be used as
      weapons of terrorism.
AB  - The authors analyzed a database of acute chemical releases to describe
      characteristics of chemicals that may be used as weapons of terrorism. Chemicals
      of primary concern (Priority I) on the Chemical Terrorism Listing of the Centers
      for Disease Control and Prevention were cross-referenced with data for 1993-2002
      from the Hazardous Substances Emergency Events Surveillance (HSEES) system. HSEES
      captured 58,043 single-substance releases of 2,366 chemicals during this time
      period. The 48 Priority I chemicals accounted for 11,567 (20 percent) of the
      releases, while representing only 2.0 percent of reported chemicals. Events
      involving Priority I chemicals resulted in twice as many victims, more injured
      members of the general public, more victims treated at hospitals, a higher
      frequency of respiratory irritation, more evacuations, more people evacuated per
      event, and more decontaminations than did all other HSEES events. Industry,
      responders, and hospitals should consider the results of this analysis in
      preparing for and responding to acute chemical releases.

PMID- 16910104
TI  - Hepatitis A in a food worker and subsequent prophylaxis of restaurant patrons.
AB  - A laboratory-confirmed case of hepatitis A was reported to Tri-County Health
      Department (TCHD) in Colorado, and the infected person was subsequently
      determined to have been a food worker at a local restaurant during the period of
      infectiousness. After conducting a public health risk assessment, TCHD decided to
      offer immune globulin (IG) to potentially exposed restaurant patrons. A two-day
      clinic in Adams County, Colorado, administered IG to 693 individuals. Planning,
      implementation, and evaluation of this clinic used a total of 900 staff hours and
      had a financial cost of dollar48,300. No additional restaurant employees became
      ill, and no secondary cases of hepatitis A were reported within the community.
      The mass-prophylaxis clinic was an important public health measure taken to
      prevent the potential spread of illness. The experience also provided relevant
      hands-on emergency-preparedness training that can be applied in other settings.

PMID- 16910105
TI  - A comparison of environmental legislation and regulation in New Zealand and the
      United States.

PMID- 16910106
TI  - The ethical dilemma of genetically modified food.

PMID- 16910107
TI  - The role of environmental health practitioners in a public health emergency.

PMID- 16910108
TI  - On "H5N1: A special report--What is the threat and why should the environmental
      health profession be concerned?".

PMID- 16910109
TI  - A source of light and energy for our profession!

PMID- 16910110
TI  - [Mandibular fractures in children. Apropos of 20 cases].
AB  - Authors report their experiences about the caring for child mandible fractures at
      Yalgado Ouedraogo University Hospital Centre, CHUYO. These fractures constitute
      day-to-day relative immediate emergencies. The techniques of retention used after
      bone setting are various. Ligatures with steel thread are frequently used. The
      retention is shortened because of the quick strengthening noticed in child. The
      satisfying results reveal the necessity of classical retention and ligatures with
      steel thread in jawbone fractures.

PMID- 16910111
TI  - Occlusion in the primary dentition. Part 1: A preliminary report on comparison of
      antero-posterior relationships and spacing among children of the major Nigerian
      ethnic groups.
AB  - This paper compares the antero-posterior occlusal pattern and arch spacing in the
      primary dentition of Nigerian children from the 3 major ethnic groups in the
      country Ibo, Yoruba and Hausa tribes. This is a cross-sectional epidemiological
      study involving eight randomly selected pre-primary schools and day-care centers
      in Ibadan and Lagos cities of Nigeria. Two hundred and sixty-nine 3-5-year-old
      children consisting of 125 (46.5%) males and 144 (53.6%) females were examined. A
      two-stage sampling method was adopted. The occlusions of the children were
      assessed according to the criteria by Foster and Hamilton, under natural
      illumination in their schools premises. Chi-square statistic was used to analyse
      the data. No statistically significant differences were observed in the molar and
      canine relationships among the ethnic groups (p > 0.05). Highly statistically
      significant differences were noted in relation to spacing of the arches (p =
      0.001) in both the anterior and posterior segments. Also, statistically
      significant differences were found in relation to post canine spaces (p < 0.05)
      but not with pre-canine spaces. Spacing was found most in the Ibo ethnic group
      children. Although no statistically significant ethnic differences were found in
      the molar relationships of the study sample, very statistically significant
      differences were revealed in the spacing of the arches in both incisor and molar
      regions.

PMID- 16910112
TI  - [Caries morbidity in the odonto-stomatologic services in Yaounde, Cameroon].
AB  - In our regions, it is believed that dental decay is an illness without prestige
      or danger for the life. It's the reason of teeth loss and many complications. The
      objective of this study was to valuate the morbidity of this pathology in odonto
      stomatology services. With an average of 4.5 teeth decays per person and a
      morbidity index of 0.15; dental carie concern all socio-professional levels,
      without distinction of age or sex. Women seem more vulnerable to teeth decay, and
      they consult services more than men. We are potential edentulous because of
      dental decay, if preventive and training measures in mouth and tooth healths are
      not taken in our country.

PMID- 16910113
TI  - Oral health attitudes and behaviour among patients in a tertiary hospital.
AB  - Oral health attitude and behaviour among patients in a Nigerian tertiary Hospital
      was investigated. About 177 patients participated via a self-administered
      questionnaire which was completed anonymously within 5 minutes. No patient had
      any fore knowledge of the questions. About 63.2% have visited dental office,
      53.4% visited only when in ache, 65.6% brushed more frequently, 28.8% have gum
      bleeding on brushing and 6.8% smoked cigarette. More females (35.5%) than males
      (23.7%) live with their families. About 37.9% (females) compared to 25.4% (males)
      visit dental office, while 36.2% of females visit when in ache against males
      (19.2%). Males (26%) brush less frequently than females (39.5%). Also, while more
      females (30.5%) are satisfied with their teeth appearance than males (19.2%),
      more males (5.1%) smoked than females (1.7%). Within the limitations of the
      study, generally males oral health attitude and behaviour are poorer and
      therefore, oral health campaign should be adopted for the population with special
      attention to the male gender.

PMID- 16910114
TI  - [Oro-facial manifestations during AIDS/HIV infection. Apropos of 60 cases seen at
      the Ambulatory Treatment Center in Ouagadougou and at the Yalgado University
      Hospital Center].
AB  - The opportinistics complaints of the AIDS occur all along the episode of the
      infection and depend on the individual's body immunity and on the existence or no
      of an anti-retroviral treatment. The buccal appearences on the face are
      relatively frequent. They are dominated by the buccal mycosis, the lymphatic
      ganglion's complaints, the inflammation of gums and buccal mucous, and the tooth
      decay in our context. Some authors suggest a classification that can make easy
      their study and treatment. Complaints like the herpes simplex infection, the
      herpes zoster infection, are usually found during the symptomatic stage non AIDS,
      whereas others like KAPOSI's disease are typical to AIDS disease. The
      availlability of an anti-retroviral treatment and a specialized one strenghten
      the efficiency of the reimbursement and improve the prognosis.

PMID- 16910115
TI  - Oral health status of 1500 university students in Toulouse France.
AB  - BACKGROUND: The purpose of this study was to assess the oral health status among
      a population of students enrolled in the first year at the Paul Sabatier
      University in Toulouse (France), and to compare the results with those of similar
      investigations. METHODS: An epidemiologic survey of 1,500 students at the Centre
      for Preventive Medicine at Paul Sabatier University (UPS) will enable us to
      obtain the prevalence of certain variables such as DMFT, sugar consumption, tooth
      brushing frequency, and mouthwash use, through a structured questionnaire and a
      standardised oral health examination. RESULTS: The Decayed, Missing and Filled
      Teeth (DMFT) index of these students was 4.4 (Standard Deviation = 3.72) (D = 1,
      M = 0.042 F = 3,454). Of the 1500 subjects, 27.6% smoke, while 43% eat sweets on
      a regular basis. The female students are more careful with their dental health
      (tooth-brushing frequency and mouthwash use are statistically significant (p <
      0.001). CONCLUSION: Although the result of the DMFT index is lower in comparison
      to similar previous studies, a decrease in dental caries seems certain. The
      multifactorial knowledge of the caries aetiology motivates us to search for new,
      more sensitive indexes.

PMID- 16910116
TI  - [Prevalence of anemia in patients undergoing dental care. A survey of 168
      patients in the dental offices of the National Institute of Public Health in
      Adjame (Abidjan)].
AB  - The aim of this study is the assessment of anaemia importance in patients
      consulting the dentist. 168 patients, all kind, of the dental office of the
      National Institute of Public Health of Abidjan, from 3 years ago, whom
      haematological statute is unknown are selected. Each person, after filling out a
      survey paper, is submitted to dental and haematological investigations. As
      result, 33% of our patients have anaemia. 95% of them are women. Pupils represent
      48% of the anaemic.

PMID- 16910117
TI  - An empirical, quantitative approach to predict the reactivity of some substituted
      aromatic compounds towards reactive radical species (Cl2-*, Br2-*, *NO2, SO3-*,
      SO4-*) in aqueous solution.
AB  - The Hammett approach, applied to the reaction of various classes of aromatic
      compounds with the radicals Cl2-*, Br2-*, *NO2, SO3-*, and SO4-* yielded good
      predictive models, supported by high values of the correlation coefficient r2 in
      the case of phenols with Cl2-* and of phenolates with *NO2 and SO3-*. Lower but
      statistically significant correlation coefficients could be obtained for
      benzoates with Cl2-*, phenolates with Br2-*, and benzoates and anisoles with SO4
      *.

PMID- 16910118
TI  - Titration curves: a useful instrument for assessing the buffer systems of acidic
      mining waters.
AB  - BACKGROUND, AIMS AND SCOPE: The acidification of mine waters is generally caused
      by metal sulfide oxidation, related to mining activities. These waters are
      characterized by low pH and high acidity due to strong buffering systems. The
      standard acidity parameter, the Base Neutralization Capacity (BNC), is determined
      by endpoint titration, and reflects a cumulative parameter of both hydrogen ions
      and all buffering systems, but does not give information on the individual buffer
      systems. We demonstrate that a detailed interpretation of titration curves can
      provide information about the strength of the buffering systems. The buffering
      systems are of importance for environmental studies and treatment of acidic
      mining waters. METHODS: Titrations were carried out by means of an automatic
      titrator using acidic mining waters from Germany and Canada. The curves were
      interpreted, compared with each other, to endpoint titration results and to
      elemental concentrations contained therein. RESULTS AND DISCUSSION: The titration
      curves were highly reproducible, and contained information about the strength of
      the buffer systems present. Interpretations are given, and the classification and
      comparison of acidic mining waters, by the nature and strength of their buffering
      systems derived from titration curves are discussed. The BNC-values calculated
      from the curves were more precise than the ones determined by the standard
      endpoint titration method. Due to the complex buffer mechanisms in acidic mining
      waters, the calculation of major metal concentrations from the shape of the
      titration curve resulted in estimates, which should not be confused with precise
      elemental analysis results. CONCLUSION: Titration curves provide an inexpensive,
      valuable and versatile tool, by which to obtain sophisticated information of the
      acidity in acidic water. The information about the strength of the present buffer
      systems can help to understand and document the complex nature of acidic mining
      water buffer systems. Finally, the interpretation of titration curves could help
      to improve treatment measurements and the ecological understanding of these
      acidic waters.

PMID- 16910119
TI  - Ecotoxic effect of photocatalytic active nanoparticles (TiO2) on algae and
      daphnids.
AB  - BACKGROUND: Due to their large potential for manifold applications, the use of
      nanoparticles is of increasing importance. As large amounts of nanoparticles may
      reach the environment voluntarily or by accident, attention should be paid on the
      potential impacts on the environment. First studies on potential environmental
      effects of photocatalytic TiO2 nanoparticles have been performed on the basis of
      widely accepted, standardized test systems which originally had been developed
      for the characterization of chemicals. The methods were adapted to the special
      requirements of testing photocatalytic nanoparticles. METHODS: Suspensions of two
      different nanoparticles were illuminated to induce their photocatalytic activity.
      For testing, the growth inhibition test with the green alga Desmodesmus
      subspicatus and the immobilization test with the daphnid Daphnia magna were
      selected and performed following the relevant guidelines (algae: ISO 8692, OECD
      201, DIN 38412-33; daphnids: ISO 6341, OECD 202, DIN 38412-30). The guidelines
      were adapted to meet the special requirements for testing photocatalytic
      nanoparticles. RESULTS: The results indicate that it is principally possible to
      determine the ecotoxicity of nanoparticles. It was shown that nanoparticles may
      have ecotoxicological effects which depend on the nature of the particles. Both
      products tested differ in their toxicity. Product 1 shows a clear concentration
      effect curve in the test with algae (EC50: 44 mg/L). It could be proven that the
      observed toxicity was not caused by accompanying contaminants, since the toxic
      effect was comparable for the cleaned and the commercially available product. For
      product 2, no toxic effects were determined (maximum concentration: 50 mg/L). In
      the tests with daphnids, toxicity was observed for both products, although the
      concentration effect-curves were less pronounced. The two products differed in
      their toxicity; moreover, there was a difference in the toxicity of illuminated
      and non-illuminated products. DISCUSSION: Both products differ in size and
      crystalline form, so that these parameters are assumed to contribute to the
      different toxicities. The concentration-effect curves for daphnids, which are
      less-pronounced than the curves obtained for algae, may be due to the different
      test organisms and/or the differing test designs. The increased toxicity of pre
      illuminated particles in the tests with daphnids demonstrates that the
      photocatalytic activity of nanoparticles lasts for a period of time. CONCLUSION:
      The following conclusions can be drawn from the test results: (I) It is
      principally possible to determine the ecotoxicity of (photocatalytic)
      nanoparticles. Therefore, they can be assessed using methods comparable to the
      procedures applied for assessing soluble chemicals. (II) Nanoparticles may exert
      ecotoxicological effects, which depend on the specific nanoparticle. (III)
      Comparable to traditional chemicals, the ecotoxicity depends on the test
      organisms and their physiology. (IV) The photocatalytic activity of nanoparticles
      lasts for a relevant period of time. Therefore, pre-illumination may be
      sufficient to detect a photocatalytic activity even by using test organisms which
      are not suitable for application in the pre-illumination-phase. RECOMMENDATIONS
      AND PERSPECTIVES: First results are presented which indicate that the topic
      'ecotoxicity and environmental effects of nanoparticles' should not be neglected.
      In testing photocatalytic nanoparticles, there are still many topics that need
      clarification or improvement, such as the cause for an observed toxicity, the
      improvement of the test design, the elaboration of a test battery and an
      assessment strategy. On the basis of optimized test systems, it will be possible
      to test nanoparticles systematically. If a potential risk by specific
      photocatalytic particles is known, a risk-benefit analysis can be performed and,
      if required, risk reducing measures can be taken.

PMID- 16910120
TI  - Isolation and identification of antialgal compounds from the leaves of
      Vallisneria spiralis L. by activity-guided fractionation.
AB  - BACKGROUND, AIMS AND SCOPE: Vallisneria spiralis Linn., a common submerged
      macrophyte, is widely available in quiet waters of lakes, ponds, marshes and
      streams in Southeast Asia. V. spiralis plays a significant role not only in
      decreasing eutrophication of water body for its productivity, but also in
      inhibiting the growth of blue-green algae? The aim of the paper involves the
      isolation and identification of allelochemicals from extracts of V. spiralis by
      activity-guided fractionation and column chromatography. METHODS: Leaves of V.
      spiralis was washed free of debris, air-dried and refluxed in 95% EtOH. The
      extract was isolated using column chromatography and fractionation with antialgal
      activity. Potential allelochemicals were analyzed by high-resolution gas
      chromatography-mass spectrometry (HRGC-MS). RESULTS: Two fractions with strong
      antialgal activity were isolated using column chromatography and activity-guided
      fractionation from the extract of V. spiralis. 2-Ethyl-3-methylmaleimide,
      dihydroactinidiolide and 4-oxo-beta-Ionone were identified in the first fraction,
      and 3-hydroxy-5,6-epoxy-beta-ionone, loliolide, 6-hydroxy-3-oxo-alpha-ionone and
      an unknown compound in the second fraction. They had strong inhibitory effects on
      Microcystis aeruginosa Kutz. DISCUSSION: 2-Ethyl-3-methylmaleimide is a byproduct
      of photooxidation of chlorophyll, and five other compounds identified were
      derivatives of beta-carotene. HRGC-MS and derivatization technology were used to
      identify and confirm their molecular structures. The formula of the unknown
      compound was C16H19NO4. Metabolites of plant pigments had strong inhibitory
      activities on growth of algae. CONCLUSIONS: Six compounds had been identified in
      V. spiralis, among them, 2-ethyl-3-methylmaleimide was the main allelochemical,
      and derivatives of ionone were also potential allelochemicals. RECOMMENDATIONS
      AND PERSPECTIVES: The results of our research could help us to study further
      mechanisms of inhibitory effect on algae and develop new potential antialgal
      substances.

PMID- 16910121
TI  - Enhancing diatom growth by using zeolites to change seawater composition.
AB  - AIMS AND SCOPE: The purpose of this study was to test whether two zeolites
      produced synthetically (products of zeolitic nature, PZN) could influence either
      the yield of a diatom culture or the chemical changes in the cultures. For this
      purpose, Phaeodactylum tricornutum was used as test organism in a culture medium
      of natural seawater enriched with N and P having negligible amounts of ammonia.
      METHODS: The PZN ZEBEN-06 and ZESTEC-56 were used in parallel experiments. The
      composition of trace metals and organic compounds with chelate activity in the
      culture media, were determined by anodic or cathodic stripping voltammetry. The
      impact of leaching silicon on the algal yield was evaluated by comparing the
      growth in the presence or absence of PZN, in seawater enriched or not-enriched
      with silicon. RESULTS AND CONCLUSIONS: Both PZN significantly promoted the algal
      yield even in the absence of added silicon, a limiting nutrient for diatom
      growth. The PZN acted as a silicon buffer while providing a source of silicon
      required for growth. In addition, PZN released into the seawater small but
      significant amounts of the limiting micro-nutrient manganese (its concentration
      doubled during the experiments), while simultaneously removing relatively high
      quantities of zinc from the seawater. The presence of PZN inhibited the releasing
      of chelated compounds. These changes (sorption/desorption) caused by the PZN in
      the concentrations in the solutions used as culture media of P. tricornutum were
      probably responsible for the differences in both the diatom growth and exudation
      observed in the tested cultures.

PMID- 16910122
TI  - Suitability of Crangonyx pseudogracilis (Crustacea: Amphipoda) as an early
      warning indicator in the multispecies freshwater biomonitor.
AB  - BACKGROUND: Biological monitors are increasingly important in 'Biological Early
      Warning Systems' (BEWS) for monitoring water quality. This study examines the
      freshwater amphipod Crangonyx pseudogracilis as a potential new indicator species
      when used in the Multispecies Freshwater Biomonitor (MFB). The MFB is an online
      continuous biomonitor which uses impedance conversion to record behavioural
      responses of vertebrates and invertebrates. METHODS: Four experiments were
      undertaken to establish: (1) if the electrical field generated by the MFB
      affected the organisms' behaviour, (2) if defined behaviours and their response
      to a gradient of ammonium chloride could be detected by the MFB, (3) if there was
      variation in the behaviour of C. pseudogracilis over a diel cycle, and (4) if
      behaviour changed significantly in response to a pulse of ammonium chloride.
      RESULTS AND DISCUSSION: Results showed no significant effect of the MFB's current
      on behaviour of C. pseudogracilis. Four behaviours; swimming, walking, grooming
      and inactivity, were observed and identified in the MFB. In the MFB, each
      behaviour changed significantly in response to an increasing gradient of ammonium
      chloride exposure. The MFB also detected increases in nocturnal activity by C.
      pseudogracilis. The MFB also detected a significant increase in activity after a
      pulse of ammonium chloride. CONCLUSION: The range of behaviours exhibited by
      Crangonyx pseudogracilis, together with its ease of culture, suggest future
      potential of this species as an indicator species for the Multispecies Freshwater
      Biomonitor. RECOMMENDATIONS AND OUTLOOK: Further testing is required over a range
      of toxicants and concentration gradients to establish threshold responses and the
      full compliment of behaviours that could be useful in online biomonitoring.

PMID- 16910123
TI  - Triadimefon causes branchial arch malformations in Xenopus laevis embryos.
AB  - BACKGROUND, AIMS AND SCOPE: Triazole-derivatives are potent antifungal agents
      used as systemic agricultural fungicides and against fungal diseases in humans
      and domestic animals. They act by inhibiting the cytochrome P-450 conversion of
      lanosterol to ergosterol, thus resulting in faulty fungal cell wall synthesis.
      Some data have been published about the teratogenic activity of triazoles on
      rodent embryos: Hypoplasias, abnormal shape, agenesis of the branchial arches,
      for example, were reported as typical induced malformations. Unfortunately, no
      data are available on the embryotoxicity of these compounds in amphibians,
      despite the increasing concern among the scientific community about the
      phenomenon of global amphibian population declines. The aim of the present work
      is to evaluate the embryo-lethal and teratogenic potentials of Triadimefon (FON),
      a triazole-derivative widely used as an antimycotic in agriculture, by the test
      FETAX (Frog Embryos Teratogenic Assay, Xenopus) with particular attention being
      paid to the analysis of branchial arch malformations. METHODS: Xenopus laevis
      embryos were exposed continuously from stage 9 to increasing concentrations of
      FON and analyzed at stage 47 for mortality and teratogenicity (group I) to
      determine the median lethal (LC50) and teratogenic (TC50) concentrations. Another
      two pools of larvae were exposed to FON for a 2 hour period at early gastrula
      (Group II) or neurula (Group III) stages to verify which period of development is
      the most sensitive to FON. The malformations observed were further investigated
      by histological section and cartilage staining with Alcian blue. RESULTS AND
      DISCUSSION: The assay has estimated LC50 and TC50 values of 63.8 microM and 2.73
      microM, respectively; the resulting TI (Teratogenic Index = LC50/TC50) value of
      23.4 has underlined the very high teratogenic risk associated with this compound.
      Neurulation was more sensitive to FON exposure than gastrulation, since the TC50
      estimated values for group III (neurula exposed) specimens was 7.6 times lower
      than those of group II (gastrula exposed). Interestingly, for each group
      analyzed, 100% of malformed embryos showed alterations at branchial arch derived
      cartilages: Anterior cartilages were reduced, missing, fused or incorrectly
      positioned while gill cartilages were altered only in the most severely affected
      specimens. In some cases these malformations were associated with
      hyperpigmentation. Our results support the hypothesis that FON can interfere with
      Neural Crest Cell (NCC) migration, since craniofacial components and melanophores
      are derived from neural crest material. CONCLUSION: In conclusion, our data show
      Triadimefon to be a potent teratogen able to induce specific craniofacial
      malformation in Xenopus laevis embryos, probably interfering with the NCC
      migration into the branchial mesenchyme. These results are also interesting for
      ecotoxicological reasons as FON, as well as other pesticides, are likely to be
      present in water systems near agricultural or urban areas which may serve as
      habitats for developing amphibians and fishes. RECOMMENDATION AND OUTLOOK: Our
      results are in agreement with the data obtained on in vitro cultured rat embryos
      suggesting that the FON mechanism of action involves strongly conserved
      molecules. The choice of Xenopus laevis as the model organism allows us to extend
      the toxicological and teratological observations to a molecular level, in order
      to search for novel genes regulated by FON exposure.

PMID- 16910124
TI  - A biomimetic approach to the detection and identification of estrogen receptor
      agonists in surface waters using semipermeable membrane devices (SPMDs) and
      bioassay-directed chemical analysis.
AB  - GOAL, SCOPE AND BACKGROUND: Some anthropogenic pollutants posses the capacity to
      disrupt endogenous control of developmental and reproductive processes in aquatic
      biota by activating estrogen receptors. Many anthropogenic estrogen receptor
      agonists (ERAs) are hydrophobic and will therefore readily partition into the
      abiotic organic carbon phases present in natural waters. This partitioning
      process effectively reduces the proportion of ERAs readily available for
      bioconcentration by aquatic biota. Results from some studies have suggested that
      for many aquatic species, bioconcentration of the freely-dissolved fraction may
      be the principal route of uptake for hydrophobic pollutants with logarithm n
      octanol/water partition coefficient (log Kow) values less than approximately 6.0,
      which includes the majority of known anthropogenic ERAs. The detection and
      identification of freely-dissolved readily bioconcentratable ERAs is therefore an
      important aspect of exposure and risk assessment. However, most studies use
      conventional techniques to sample total ERA concentrations and in doing so
      frequently fail to account for bioconcentration of the freely-dissolved fraction.
      The aim of the current study was to couple the biomimetic sampling properties of
      semipermeable membrane devices (SPMDs) to a bioassay-directed chemical analysis
      (BDCA) scheme for the detection and identification of readily bioconcentratable
      ERAs in surface waters. METHODS: SPMDs were constructed and deployed at a number
      of sites in Germany and the UK. Following the dialytic recovery of target
      compounds and size exclusion chromatographic cleanup, SPMD samples were
      fractionated using a reverse-phase HPLC method calibrated to provide an
      estimation of target analyte log Kow. A portion of each HPLC fraction was then
      subjected to the yeast estrogen screen (YES) to determine estrogenic potential.
      Results were plotted in the form of 'estrograms' which displayed profiles of
      estrogenic potential as a function of HPLC retention time (i.e. hydrophobicity)
      for each of the samples. Where significant activity was elicited in the YES, the
      remaining portion of the respective active fraction was subjected to GC-MS
      analysis in an attempt to identify the ERAs present. RESULTS AND DISCUSSION:
      Estrograms from each of the field samples showed that readily bioconcentratable
      ERAs were present at each of the sampling sites. Estimated log Kow values for the
      various active fractions ranged from 1.92 to 8.63. For some samples, estrogenic
      potential was associated with a relatively narrow range of log Kow values whilst
      in others estrogenic potential was more widely distributed across the respective
      estrograms. ERAs identified in active fractions included some benzophenones,
      various nonylphenol isomers, benzyl butyl phthalate, dehydroabietic acid,
      sitosterol, 3-(4-methylbenzylidine)camphor (4-MBC) and 6-acetyl-1,1,2,4,4,7
      hexamethyltetralin (AHTN). Other tentatively identified compounds which may have
      contributed to the observed YES activity included various polycyclic aromatic
      hydrocarbons (PAHs) and their alkylated derivatives, methylated benzylphenols,
      various alkyl-phenols and dialkylphenols. However, potential ERAs present in some
      active fractions remain unidentified. CONCLUSIONS AND OUTLOOK: Our results show
      that SPMD-YES-based BDCA can be used to detect and identify readily
      bioconcentratable ERAs in surface waters. As such, this biomimetic approach can
      be employed as an alternative to conventional methodologies to provide
      investigators with a more environmentally relevant insight into the distribution
      and identity of ERAs in surface waters. The use of alternative bioassays also has
      the potential to expand SPMD-based BDCA to include a wide range of toxicological
      endpoints. Improvements to the analytical methodology used to identify ERAs or
      other target compounds in active fractions in the current study could greatly
      enhance the applicability of the methodology to risk assessment and monitoring
      programmes.

PMID- 16910125
TI  - Spatiotemporal features of severe air pollution in northern Taiwan.
AB  - BACKGROUND, AIMS AND SCOPE: This research attempted to identify the dominant
      factors simultaneously affecting the airborne concentrations of five air
      pollutants with principal component analysis and to determine the
      meteorologically related parameters that cause severe air-pollution events.
      According to the definition of subPSI and PSI values through the U.S. EPA, the
      historical raw data of five criteria air pollutants, SO2, CO, O3, PM10 and NO2,
      were calculated as daily subPSI values. In addition to the airborne
      concentrations, this study simultaneous collected the surface meteorological
      parameters of the Taipei meteorological station, established by the Central
      Weather Bureau. METHODS: Principal component analysis was conducted to screen
      severe air pollution scenarios for five air pollutants: SO2, CO, O3, PM10 and
      NO2. The concentrations of various air pollutants measured at 17 air-quality
      stations in northern Taiwan from 1995 to 2001 were transformed into daily subPSI
      values. The correlation analysis of the five air pollutants and four
      meteorological parameters (wind speed, temperature, mixing height and ventilation
      rate) were included in this research. After screening severe air pollution
      scenarios, this study recognized the synoptic patterns easily causing the severe
      air-pollution events. RESULTS AND DISCUSSION: Analytical results showed that the
      eigenvalues of the first two principal components for SO2, CO, O3, PM10 and NO2
      were greater than 1. The first component of five air pollutants explained 64, 64,
      67, 76 and 63% of subPSI variance for SO2, CO, O3, PM10 and NO2, respectively.
      Only the correlation coefficient of NO2 and CO had statistically significant
      positive values (0.82); other pollutant pairs presented medium (0.4 to 0.7) or
      low (0 to 0.4) positive values. The correlation coefficients for air pollutants
      and three meteorological parameters (wind speed, mixing height and ventilation
      index) were medium or low negative values. In northern Taiwan, spring was most
      likely induced high concentrations and the component scores of the first
      component for SO2, CO, PM10 and NO2; summer was the worst season that caused high
      O3 episodes. Consequently, the analytical results of factor loadings for the
      first principal component and emission inventory of various sources revealed that
      mobile sources were dominant factors affecting ambient air quality in northern
      Taiwan. CONCLUSION: According to the results of principal component analysis for
      the five air pollutants, the first two of 17 components were cited as major
      factors and explained 71% of subPSI variance. Based on the inventory of NOx
      emissions and the isopleth diagram of factor loading for the first component,
      mobile sources in the southwest Taipei City accounted for the highest factor
      loading values and emission inventory values. Synoptic analysis and principal
      component analysis demonstrated that three types of weather patterns (high
      pressure recirculation, prefrontal warm sector and the southwesterly wind system)
      easily caused the severe air-pollution scenarios. In summary, if severe air
      pollution days occurred, the average meteorological parameters experienced
      adverse conditions for diffusing air pollutants; that is, the average values of
      wind speed, mixing height and ventilation index were lower than 2.1 ms(-1), 360 m
      and 800 m2s(-1), respectively. If one of the three synoptic patterns were to
      occur in combination with adverse meteorological conditions, severe air-pollution
      events would be developed. RECOMMENDATION AND OUTLOOK: By utilizing synoptic
      patterns, this work found three weather systems easily caused severe air
      pollution events over northern Taiwan. Analytical results showed, respectively,
      the wind speed and mixing height were less than 2.1 m/s and 360 m during severe
      air-pollution events.

PMID- 16910127
TI  - Save staffing saves lives.

PMID- 16910126
TI  - Progress in understanding the sources, deposition and above-ground fate of
      trichloroacetic acid.
AB  - AIM AND SCOPE: This paper is a companion to the recent review paper by Laturnus
      et al. (2005) on TCA in soils, presenting a complementary review of knowledge
      gaps in the sources and fate of trichloroacetic acid (TCA) in plants. MAIN
      FEATURES: The review considers the various sources of TCA precursors, including
      the question of how much atmospheric TCA comes from naturally-produced
      precursors, and addresses the implications of climate change on atmospheric TCA
      formation. Models of the conversion of precursors to TCA in the atmosphere are
      critically compared with field measurements of concentrations, deposition and
      budgets; data on the quantitative relationships between gas-phase TCA,
      particulate TCA, and TCA dissolved in rain and clouds are reviewed. Methods for
      quantifying TCA are summarised, along with a description of what the different
      techniques measure, and how results can be compared. A distinction is made
      between 'extractable' TCA and 'total' TCA in vegetation. Evidence for the various
      pathways by which TCA enters plants is given, including the in situ production of
      TCA in leaves. This leads to a better understanding of how plant tissue
      concentrations depend on uptake, production and removal rates. Finally, knowledge
      of the toxic effects of TCA on plants and TCA metabolism in plant tissues is
      summarised. RESULTS AND DISCUSSION: The discussion highlights knowledge gaps, and
      is intended to aid the reader in interpreting previously published results
      through identifying where different ways of expressing data have been used, and
      the consequent conclusions that can be drawn. CONCLUSION AND FURTHER RESEARCH
      DIRECTIONS: Recommendations are given for future research directions--in
      identifying precursor sources, quantifying heterogeneous atmospheric processes,
      recognising and quantifying uptake pathways, and elucidating the biochemical
      mechanisms involved in sequestering and degrading TCA inside leaves.

PMID- 16910128
TI  - Life stories of depressed adult women in peri-urban Namibia.
AB  - The problems women in peri-urban Namibia are faced with are multi-dimensional.
      Like women in other communities they face the pressure of having a number of
      responsibilities, namely working, being a wife and mother, taking care of their
      families and perhaps caring for aging parents. Sometimes the pressure can be too
      overwhelming to manage. As a result, many women become depressed. Studies on
      depression among black African women in Namibia could not be traced. It was
      therefore considered to find out how women suffering from depression from this
      part of the world tell their life stories. The purpose of the study was two-fold:
      Firstly, to explore and describe the life stories of depressed adult women in
      peri-urban Namibia, and secondly to use the information obtained to describe
      guidelines for psychiatric nurses working with these patients at psychiatric
      outpatient clinics as well as in the community. A qualitative phenomenological
      research design of an explorative, descriptive and contextual nature was used.
      The researcher approached the subjects and their experiences with an open mind.
      Ten depressed adult women between 21-55 years were involved in the research. The
      researcher strived to adhere to the principles of trustworthiness. To ensure this
      Guba's model (in Krefting, 1991: 217) of trustworthiness was adopted. All the
      interviews were analysed following Tesch's method (Creswell, 1994: 154-55). The
      services of an independent coder were obtained. The results indicated that
      impaired interpersonal interactions and stressful life events have a negative
      influence on the daily life of women leading to the development of depressive
      symptoms. Guidelines to support psychiatric nurses working with depressed women
      were drawn up.

PMID- 16910129
TI  - Patients' satisfaction with government health care and services in the Taung
      district, North West Province.
AB  - This was a descriptive study that determined patients' satisfaction with health
      care in the Taung district state health institutions, North West Province. One
      hospital, three health centres and five clinics were randomly selected, and
      consecutive patients were recruited at outpatients during 17 May 2000 - 17 June
      2000. The patients completed a questionnaire regarding the service or care
      provided. Five hundred and sixty seven patients participated in the study. The
      median age was 30 years, and most patients were female (76.7%). More than half of
      patients (56.8%) were not satisfied with the availability of medicines and other
      supplies. Approximately two thirds of patients (65.2%) did not know about the
      quality of telephone services rendered. There was a high level of dissatisfaction
      (63.1%) among patients regarding accessing doctors after hours. Most patients
      were satisfied with the general attitude of health workers (62.1%) but 21.2% were
      dissatisfied. Few (11.7%) patients felt rushed during consultation. Most patients
      felt they received good health education when their illness was discussed
      (74.6%). Words and explanations used were easy to understand (76.7%); and they
      were not discouraged from asking questions (69.9%, n=539). Generally the level of
      satisfaction among the patients was high except for difficulty in accessing
      doctors after hours and lack of medicines.

PMID- 16910130
TI  - Training primary care nurses to conduct alcohol screening and brief interventions
      in South Africa.
AB  - Although progress has been made in developing a scientific basis for alcohol
      screening and brief intervention (SBI), training packages are necessary for its
      widespread dissemination in primary care settings in developing societies. Using
      a training package developed by the World Health Organisation 121 nurses from one
      rural site (29 clinics in Vhembe District) and one urban site (3 clinics and 6
      mobile clinics in Polokwane/ Seshego) in South Africa were compared before and
      after SBI training regarding knowledge and attitudes, and the subsequent practice
      of SBI in routine clinical practice. Although the training effects were at times
      moderate, all changes were in a direction more conducive to implementing SBI.
      Health care providers significantly increased in knowledge, confidence in SBI and
      higher self-efficacy in implementing SBI at follow-up after 9 months after
      receiving the training. When delivered in the context of a comprehensive SBI
      implementation programme, this training is effective in changing providers'
      knowledge, attitudes, and practice of SBI for at-risk drinking.

PMID- 16910131
TI  - Occupational stress of nurses in South Africa.
AB  - The objective of this study was to examine the construct validity and reliability
      of the Nursing Stress Indicator (NSI) and to identify differences between
      occupational stressors of professional and enrolled nurses. A cross-sectional
      survey design was used. A sample of professional nurses (N = 980) and enrolled
      and auxiliary nurses (N = 800) in South Africa was used. The NSI was developed as
      measuring instrument and administrated together with a biographical
      questionnaire. Five reliable stress factors, namely Patient Care, Job Demands,
      Lack of Support, Staff Issues, and Overtime were extracted. The most severe
      stressors for nurses included health risks posed by contact with patients, lack
      of recognition and insufficient staff. Watching patients suffer, demands of
      patients and staff issues were also severe stressors for professional nurses. The
      severity of stressors was higher for professional nurses (compared with enrolled
      and auxiliary nurses). Organisations that employ nurses should implement
      programmes to monitor and manage stress, specifically regarding staff issues and
      job demands.

PMID- 16910132
TI  - Medical practice in Graeco-roman antiquity.
AB  - The roots of modern medicine can be traced back to the 5th century BC when
      Hippocratic rational medicine originated on the Greek islands of Cos and Cnidos.
      In this study we examine the way in which practitioners conducted their
      profession in Graeco-Roman times, as well as their training. Medical training was
      by way of apprenticeship with recognized doctors, but no qualifying examinations
      existed and the standard of practice thus varied enormously. Even in the Roman
      era the vast majority of medical doctors were Greek and in private practice as
      itinerant physicians. Civic doctors in the paid service of local communities
      appeared in Greek society from the 5th century BC onwards, but much later in Rome
      - probably as late as the 4th century AD. Rome's unique contributions to medicine
      lay in public health measures (e.g. their aqueducts, public baths and sewages
      systems) and an excellent medical service for their armies and navy. Hospitals
      (valetudinaria) were established for military purposes and for slaves on large
      Roman estates from the 1st century BC, but civic hospitals for the general public
      originated as late as the 4th century AD. The Greek medical schools of Cos and
      Cnidos were eventually superseded by the school of Alexandria in Egypt and
      towards the end of the Roman Empire by that of Carthage in northern Africa. Its
      gradual demise in the Christian era lowered the curtain on original medical
      endeavours during antiquity.

PMID- 16910133
TI  - Health aspects of sanitation among Eastern Cape (EC) rural communities, South
      Africa.
AB  - A descriptive study was conducted to determine the health aspects of sanitation
      among rural communities of the EC. A purposive sample of 145 villagers was drawn
      from 14 villages selected through systematic random sampling. Of these, 71 were
      male and 74 were female. The 145 participants were divided into 14 groups (M = 10
      participants) by community and randomly assigned to 14 community-based trained
      facilitators. Each facilitator administered Dunker's (2001) KAP tool for hygiene
      to the assigned group. The responses from all the groups were collated and
      analysed. Communities' health was generally not considered good (78.6%) because
      of limited clean water, lack of money to treat water and unhealthy food. The
      prevalence of diseases in the last 6 months, included: skin diseases, worms, eye
      infections, diarrhoea, bilharzias and malaria; the perceived causes of diseases
      were mainly related to poor sanitation and the suggested disease prevention
      methods were sanitation improvement related. Institutional capacity was generally
      lacking as more than 50% of the communities did not have sanitation committees
      and environmental health officers (98.3%); health (64.3%) and water
      (57.1%)committees. The results have implications for policy-makers, programme
      planners, academics and practitioners in the field of water and sanitation in
      terms of policy and programme formulation, curriculum development, and service
      delivery.

PMID- 16910134
TI  - Haemorrhage in pregnancy: information given to women in Chiradzulu (Malawi).
AB  - Advising women on haemorrhage in pregnancy could be viewed as an integral aspect
      of maternal health care in Malawi. The WHO (1999) confirmed that haemorrhage in
      pregnancy was not only a direct reason for maternal mortality but also a major
      cause of maternal death. The question on the nature of information that midwives
      and traditional birth attendants (referred to as TBA's) in the Chiradzulu
      district in Malawi gave with regard to haemorrhage in pregnancy, therefore arose.
      Research available focused on the women's knowledge about the complications of
      pregnancy but not on the nature of information women received from midwives and
      TBA's. This study explored and described the nature of information that was given
      to rural women in the Chiradzulu district by the midwives and TBA's regarding
      haemorrhage in pregnancy. The findings revealed that although both the midwives
      and TBA's included important information about haemorrhage in pregnancy, there
      were deficiencies in some critical areas. Examples of these deficiencies were the
      definition of haemorrhage in pregnancy; the predisposing factors for antepartum
      and postpartum haemorrhage and deficiencies in the nature of information on the
      management and referral of haemorrhaging patients.

PMID- 16910135
TI  - Strategies to improve the performance of learners in a nursing college. Part I:
      Issues pertaining to nursing education.
AB  - The aim of this contextual, exploratory, descriptive and qualitative study was to
      describe strategies to improve the performance of learners in a nursing college.
      The article seeks to deal with factors relating to nursing education that
      contribute to the poor performance of learners and to outline related strategies
      to improve the situation. Three focus group interviews were conducted. One group
      was formed by seven tutors, and the other two groups were formed by fourth-year
      learners following a four-year comprehensive diploma course. All participants
      voluntarily took part in the study. Data was analyzed using the descriptive
      method of open coding by Tesch (in Creswell, 1994:154-156). Trustworthiness was
      ensured in accordance with Lincoln and Guba's (1985:290-326) principles of
      credibility, conformability, transferability and dependability. The findings were
      categorized into issues pertaining to nursing education as follows: curriculum
      overload; lack of theory and practice integration; teaching and assessment
      methods that do not promote critical thinking; tutors' lack of skills and
      experience; inadequate preparation of tutors for lectures; insufficient knowledge
      of tutors regarding outcomes-based education approach to teaching and learning;
      inadequate process of remedial teaching; discrepancies between tutors' marking;
      lack of clinical role-models and high expectations from the affiliated university
      as regards standards of nursing development programme by the staff development
      committee of the nursing college under study for implementation. Future research
      should focus on the effectiveness of the described strategies to improve the
      learners' performance. It is also recommended that similar studies be conducted
      or replicated in other nursing colleges to address the problem of poor
      performance of learners engaged in a four-year comprehensive diploma course.

PMID- 16910136
TI  - Strategies to improve the performance of learners in a nursing college. Part II:
      Issues pertaining to management, attitudes and values.
AB  - This article forms part two of a bigger study that was conducted in a nursing
      college to explore and describe the reasons for the poor performance of learners.
      Part one of the study dealt with the issues pertaining to education, while this
      article (part two) seeks to describe issues pertaining to management, attitudes
      and values that lead to the poor performance of learners in the nursing college
      under study. A qualitative, exploratory and descriptive design that was
      contextual in nature was employed, and three focus groups interviews were
      conducted. Seven tutors formed one group while other two groups were formed by
      fourth-year learners following a comprehensive diploma course. All participants
      voluntarily participated in the study. Data was analyzed using the descriptive
      method of open coding in accordance with Tesch's protocol (in Creswell, 1994:154
      156). Trustworthiness was ensured using the following principles: credibility,
      conformability, transferability and dependability (Lincoln & Guba 1985:290-326).
      Findings were categorized into issues pertaining to management, attitudes and
      values that had an influence on the poor performance of learners as follows:
      MANAGEMENT: Inadequate resources and study facilities; policies that change
      frequently; tutors' dissatisfaction with regard to staff development, the lack of
      involvement by management and lack of management support, staff shortage and
      maldistribution of staff members; ineffective selection process of learners;
      inconsistent regulations, and too many of them; policies and procedures resulting
      in confusion and poor discipline. Attitudes and values: Tutors' lack of
      motivation and interest, lack of respect by learners and no team work among
      tutors. Through a conceptualization process and the recommendations by
      participants, strategies to improve the learners' performance were described. It
      is recommended that these strategies be submitted to the staff development
      committee for implementation and future follow-up research be undertaken to
      determine the effectiveness of the strategies. It is also recommended that other
      nursing colleges replicate the study within their context.

PMID- 16910137
TI  - A needs analysis for a non-abusive intervention programme in the School of Health
      Care Sciences at the University of Pretoria.
AB  - Due to feedback from students, student abuse during fieldwork, was brought to the
      attention of the researchers. The study aimed to determine whether a need for a
      non-abusive intervention programme (NIP) existed amongst the School of Health
      Care Science students at the University of Pretoria. All students enrolled at the
      School of Health Care Sciences completed a questionnaire. An overwhelming
      response indicated that the majority of students (95.85%) have a need for a non
      abusive intervention programme (NIP). A significant need was identified
      especially among Nursing-, Physiotherapy- and Radiography students, 2nd and 4th
      year students, and within a psychiatric fieldwork setting. Two surprise findings
      were firstly, that students who have no history of abuse have a greater need for
      an intervention programme than students with a history of abuse. Secondly
      superiors in the field are responsible for the majority of abusive incidences
      reported by students. The implementation of a non-abusive intervention programme
      (NIP) to help students handle abusive incidences effectively and humanely is
      strongly recommended.

PMID- 16910138
TI  - Becoming a mother: teenage mothers' experiences of first pregnancy.
AB  - The purpose of this study was firstly to explore and describe the experiences of
      teenage mothers of first pregnancy. Secondly, to develop guidelines of a support
      programme that is contextual and relevant to the needs of teenage mothers. The
      guidelines are aimed at assisting midwives in meeting the needs of teenage
      mothers. An exploratory, descriptive, contextual and qualitative design was used.
      The phenomenological approach was implemented to collect and analyze data from a
      purposively selected sample of fourteen (14) teenage mothers who were pregnant
      for the first time. The model of Guba and Lincoln (1985: 301-318) was implemented
      to ensure trustworthiness in this qualitative study. Five themes emerged from the
      analysis of the data. Guidelines and recommendations for support programme were
      developed.

PMID- 16910139
TI  - [Health care preparations for a possible flu pandemic].

PMID- 16910140
TI  - [Survey of nursing roles in anesthesiology, postoperative recovery care and pain
      management in Catalonia, Spain: analysis of the current situation].
AB  - OBJECTIVE: To determine nursing functions in anesthesiology, postoperative
      recovery care, and pain management in Catalan hospitals and to analyze the roles
      of nurses in this specialty. METHODS: Development of a mail questionnaire sent to
      70 public and private hospitals in Catalonia, to be filled in and returned
      separately by the nursing supervisor and by the anesthesiology department of each
      hospital. The survey included questions on whether tasks were or were not carried
      out by nurses. RESULTS: Responses were received from 31% of nursing supervisors
      and 45% of anesthesiology departments. Only 22% of the hospitals employed nursing
      staff with duties exclusively in the anesthesiology department. Nurses took on
      more responsibilities in major outpatient surgery services and postanesthetic
      recovery care units than in other areas. Significant discrepancies were found
      between answers given by nursing supervisors and those returned by anesthesiology
      departments regarding tasks of nurses in this specialty. Items with the greatest
      agreement were those related to maintenance of material. Those with the lowest
      agreement were related to drug management. CONCLUSIONS: Although responses came
      from only a third of the target population, the information obtained suggests a
      lack of definition in Spain of nursing tasks in the field of anesthesiology. This
      situation is different from that of most European countries and of the United
      States of America.

PMID- 16910141
TI  - [Pediatric acute postoperative pain management service: 6 years' experience].
AB  - OBJECTIVE: [corrected] To describe the introduction and activities of a low-cost
      acute postoperative pain management service for children. PATIENTS AND METHODS: A
      descriptive study of patients treated with patient-controlled analgesia (PCA),
      nurse-controlled analgesia (NCA), continuous epidural analgesia (CEA), and
      patient-controlled epidural analgesia (PCEA) from October 1998 through December
      2004. We analyzed demographic information and data on most frequent surgical
      procedures, analgesic techniques, pain on our nurse observation scale, side
      effects (nausea and/or vomiting, pruritus, urinary retention, excessive sedation,
      respiratory depression), and parent and patient satisfaction. RESULTS: Three
      hundred treatments per year were performed, for a total of 1870; 46.6% were in
      children under 5 years old. Orthopedic operations with osteotomy (22.5%) and
      laparotomies (13.4%) were the most common procedures. The most frequently used
      approach was NCA (53%), followed by PCA with bolus doses (24.5%), PCA with
      infusion (16.9%), and continuous epidural analgesia or PCEA (5.6%). On the nurse
      observation scale (no pain; slight, moderate or intense pain) absence of pain or
      slight pain was observed in 82%, 90%, and 94% of the patients on days 1, 2, and 3
      after surgery. Postoperative nausea and vomiting were observed in 20% of the
      patients and respiratory depression in 0.16%. Satisfaction was good or very good
      for 98% of the parents and 94% of the children interviewed. CONCLUSIONS: The pain
      management service in our hospital was able to control postoperative pain safely
      and effectively.

PMID- 16910142
TI  - [Prevalence of type 2 diabetes in the preoperative assessment interview].
AB  - OBJECTIVES: To determine the prevalence of type 2 diabetes in preoperative
      anesthetic assessment interviews during May 2004 and to compare the results to
      prevalences reported in other studies. PATIENTS AND METHODS: Patients over the
      age of 20 years who received an assessment interview were included. Type 1
      diabetics, pregnant women, and critically ill patients were excluded. We followed
      the 1997 diagnostic guidelines of the American Diabetes Association. RESULTS: The
      prevalence of previously diagnosed type 2 diabetes was 10.3%. Three patients were
      diabetics unaware of their disease. The overall prevalence of type 2 diabetes was
      11% in this population. CONCLUSIONS: Type 2 diabetes has a high prevalence among
      surgical patients in our hospital, higher than that reported for the general
      population based on other studies.

PMID- 16910143
TI  - [Prevalence of burnout among anesthesiologists at Hospital Universitario Virgen
      Macarena de Sevilla].
AB  - Burnout, characterized by emotional exhaustion, depersonalization, and lowered
      sense of professional accomplishment, is a consequence of chronic stress. Few
      studies have been published on burnout in anesthesiology even though this
      specialty is considered particularly stressful. We surveyed members of the
      department of anesthesiology and postoperative care in our hospital, using an
      anonymous questionnaire including items on social and personal characteristics
      and the Spanish language version of the Maslach Burnout Inventory. Forty-valid
      questionnaires were returned, for a response rate of 69.4%. Mean (SD) scores were
      19.5 (9.5) points for emotional exhaustion, 7.4 (5.5) for depersonalization, and
      32.5 (9.1) for professional accomplishment. We detected high levels of emotional
      exhaustion in 19.5% of the anesthesiologists and of depersonalization in 31.7%.
      Scores reflecting low levels of sense of personal accomplishment were recorded
      for 41.4%. Scores for concern on at least 1 subscale were noted for 58.3% of the
      anesthesiologists, on 2 subscales for 21.8%, and on 3 subscales for 12.1%. No
      significant differences were detected in relation to gender, age, stage in
      professional life, or employment status. Burnout levels in our department are
      similar to those reported for anesthesiologists in other countries and detectably
      lower than those of other specialties in Spain.

PMID- 16910144
TI  - [Characteristics and distribution of normal human epidural fat].
AB  - Epidural fat provides sufficient cushion for the pulsatile movements of the dural
      sac, protects nerve structures, facilitates the movement of the dural sac over
      the periosteum of the spinal column during flexion and extension, and forms a
      pharmacologic reservoir of lipophilic substances. We review epidural fat and
      related structures, including their development during the fetal period when the
      epidural space is filled by undifferentiated loose, areolar mesenchymal tissue
      that surrounds the dural sac. In the adult, epidural fat has a continuous
      distribution and follows a certain metameric pattern. It is located mainly on the
      dorsal side of the epidural space, where it is organized in triangular capsules
      joined to the midline of the ligamentum flavum by a vascular pedicle. We consider
      the distribution of epidural fat in the axial and sagittal planes; its presence
      in the anterior, lateral and posterior epidural space; its presence in the
      cervical, thoracic and lumbar portions of the spinal column; and its
      characteristics and variations according to differing body habits and sex.
      Finally, we speculate on the possible anesthetic implications of epidural fat in
      terms of the pharmacokinetics of drugs injected into the epidural space and the
      tasks of locating the epidural space and inserting an epidural catheter during
      anesthetic procedures.

PMID- 16910145
TI  - [Transient neurological syndrome after spinal hyperbaric bupivacaine: a new
      case].
AB  - A 47-year-old woman underwent hysteroscopy and removal of an endometrial polyp
      because of irregular, acyclic bleeding of 6 months' duration. The procedure was
      carried out under spinal anesthesia. No adverse events occurred during puncture
      or surgery, or in the immediate postoperative recovery period. Recovery from the
      sensory and motor block was normal. Twenty-four hours after surgery gluteal and
      lower limb pain and paresthesia developed, with no sensory or motor deficit. The
      symptoms suggested transient neurological syndrome. This syndrome has been
      defined by pain in the lower limbs, buttocks, thighs and calves after
      uncomplicated spinal anesthesia and full recovery from the sensorimotor block
      during the immediate postoperative period (first 24 hours). The condition is self
      limiting and does not leave permanent neurological sequelae. Recent studies have
      demonstrated biochemical and anatomical changes that provide a structural basis
      for this clinical entity. According to this literature, transient neurological
      syndrome might be a mild expression of local anesthetic toxicity. Recent findings
      show that the initial injury to the nerve cell membrane, induced by high
      concentrations of local anesthetic could lead to permanent neuronal damage.

PMID- 16910146
TI  - [Anesthesia in 2 cases of resection of a renal tumor involving the vena cava].
AB  - Renal tumors can be associated with a thrombus that affects the renal vein and
      even the inferior vena cava. Radical surgery may require a 2-phase approach
      involving different anesthetic techniques: an abdominal approach for removal of
      the kidney and a thoracic approach for extraction of the thrombus, with
      extracorporeal circulation and in some cases cessation of blood circulation. We
      present 2 cases in which nephrectomy and thrombectomy were carried out with the
      support of extracorporeal circulation. The thrombus was in the renal vein and the
      inferior vena cava, extending to the outlet to the right atrium in both cases. In
      1 case a portion reached the bifurcation of the pulmonary artery. The operation
      was performed under hypothermia to reduce circulation and did not require aortic
      clamping, cardioplegia, or cessation of blood flow.

PMID- 16910147
TI  - [Bilateral axillary brachial plexus block guided by multiple nerve stimulation
      and ultrasound in a multiple trauma patient].
AB  - We present the case of a woman with multiple wounds and injuries after attempted
      suicide by jumping from a high place. She had multiple craniofacial injuries and
      fractures of both forearms requiring emergency osteosynthesis. The neurosurgeons
      requested that a level of consciousness be maintained for frequent assessment;
      therefore it was decided to provide a bilateral axillary brachial plexus block.
      The procedure was carried out with the aid of a nerve stimulator to locate a
      triple response in the left arm (radial, medial and musculocutaneous nerves) and
      with both ultrasound and double nerve stimulation in the right arm (medial and
      radial nerves). Surgery proceeded without adverse events. The location of nerves
      or nerve roots with both ultrasound and stimulators was highly useful in this
      patient in need of bilateral brachial plexus blockade. This combination, and
      ultrasound in particular, might be the technique of choice because it offers an
      image in real time and assessment of the least amount of anesthetic that seems to
      be needed for achieving a block.

PMID- 16910150
TI  - [Epidural methadone overdose].

PMID- 16910149
TI  - [Anesthetic implications for patients with the thermolabile variant of the
      methylenetetrahydrofolate reductase gene].

PMID- 16910148
TI  - [General anesthesia in an adult with Eisenmenger syndrome].

PMID- 16910151
TI  - [Anesthesia and recessive dystrophic epidermolysis bullosa].

PMID- 16910152
TI  - [Importance of electrode placement in systems for monitoring hypnosis].

PMID- 16910153
TI  - [Comments on the article "Emergency tracheostomy to resolve an unforeseen
      difficult airway].

PMID- 16910154
TI  - [Wolff-Parkinson-White pre-excitation syndrome].

PMID- 16910155
TI  - Sotalol in the treatment of fetal tachyarrhythmia.
AB  - BACKGROUND: Fetal tachycardia is an uncommon condition that if sustained may lead
      to fetal death. There is no consensus regarding the optimum treatment. The aim of
      this study was to evaluate the safety and efficacy of sotalol in the treatment of
      fetal tachycardia. METHODS: This was a retrospective study of patients treated
      for fetal tachycardia with sotalol in a pediatric cardiology department over a
      ten-year period. RESULTS: There were eight fetuses treated for supraventricular
      tachycardia and sotalol was used in six of them. Mean gestational age was 30
      weeks. None of them had congenital heart disease; two fetuses had hydrops and one
      had hydrocephalus. All had supraventricular tachycardia and two had atrial
      flutter. Drug treatment was successful in establishing sinus rhythm in five of
      the six fetuses treated with sotalol and no adverse effects were recorded in the
      mothers. There were no deaths. Supraventricular tachycardia was present in three
      infants at birth. CONCLUSIONS: In this study sotalol was successful and safe in
      the treatment of fetal tachycardia, but given the small sample size, more studies
      are needed to validate this conclusion.

PMID- 16910156
TI  - Fascicular ventricular tachycardia: experience with radiofrequency ablation.
AB  - Fascicular ventricular tachycardia (VT), the commonest form of idiopathic left
      VT, occurs more frequently in young males without structural heart disease and
      usually presents as paroxysmal palpitations. It is subdivided into two more
      common subtypes, posterior and anterior. A macro-reentrant circuit involving a
      considerable and variable extent of the left interventricular septum is presumed
      to be the underlying arrhythmogenic mechanism. A slow conduction zone with
      particular sensitivity to verapamil participates in the circuit and it seems that
      diastolic potentials (DP) represent the electrical activity in or near this zone.
      The fascicles of the left bundle appear to constitute part of the retrograde
      pathway and Purkinje potentials (PP) are assumed to represent their activation.
      In the present retrospective study, the authors review twelve cases of fascicular
      VT (ten posterior and two anterior) evaluated in the electrophysiology
      laboratory. Although initial induction was obtained in all patients,
      reproducibility was poor as a consequence of frequent contact inhibition during
      endocardial mapping of the left ventricle and this meant that ablation was not
      possible in two cases. Two cases of associated atrioventricular nodal reentrant
      tachycardia (AVNRT) and a case of associated atrioventricular reentrant
      tachycardia by a right posterior accessory pathway were documented, which suggest
      a correlated anatomic substrate. After ablation of the slow nodal pathway in one
      of the AVNRTs, fascicular VT was no longer inducible. Ablation of the fascicular
      VT was attempted in nine patients, at the tachycardia exit site (characterized by
      an early ventricular electrogram fused with a Purkinje potential) in two patients
      with anterior fascicular VT and in five patients with the posterior subtype, and
      near the slow conduction pathway (site with simultaneous recording of DP and PP)
      in the other two patients. The initial success rate with a single procedure was
      78%, two of the ablations at the tachycardia exit site failing, with no
      complications. If we include the success of a repeated case with three
      dimensional mapping, the overall success rate was 80%. Ablation of fascicular
      tachycardia appears to be a good therapeutic option with a good success rate and
      without significant adverse events. The poor reproducibility as a consequence of
      contact inhibition during endocardial left ventricular mapping is the principal
      limiting factor. With the help of currently available mapping systems, we hope
      that this limitation will disappear, as it is now possible with some devices to
      acquire accurate information on suitable sites for subsequent radiofrequency
      application with little or no contact, facilitating the ablation procedure.
      Ablation at a site with simultaneous recording of DP and PP is considered by most
      authors to be more effective than that performed at the tachycardia exit site.

PMID- 16910157
TI  - Transient left ventricular apical ballooning.
AB  - We describe the case of an elderly woman patient referred for primary angioplasty
      for acute anterior myocardial infarction, which developed after intense emotional
      stress. The coronary angiogram was surprisingly normal, but left ventriculography
      showed severe apical dilatation and dyskinesia, confirmed by echocardiography. By
      this time we suspected a syndrome of transient apical ballooning without coronary
      stenosis, which mimics acute myocardial infarction. She underwent medical therapy
      and subsequent clinical evolution was favorable, with complete recovery of left
      ventricular systolic function. We discuss the clinical setting and the
      pathophysiologic mechanisms of this syndrome.

PMID- 16910158
TI  - Morphologic, molecular and hemodynamic cardiac alterations in a model of
      nephropathy induced by puromycin aminonucleoside.
AB  - INTRODUCTION: Proteinuria and decreased glomerular filtration rate are assuming
      increased importance in defining cardiovascular risk in chronic renal
      insufficiency. The aim of this work was to study morphologic, molecular and
      hemodynamic cardiac alterations in an animal model of proteinuria and renal
      insufficiency induced by puromycin aminonucleoside (PAN). METHODS: Normotensive
      rats (n = 14) were injected with PAN (150 mg/kg, i.p.) or with vehicle. Blood
      pressure was measured daily and the animals were placed in metabolic cages for
      evaluation of urinary excretion of sodium, protein and creatinine. Fourteen days
      after PAN administration left ventricular hemodynamics were evaluated through a
      pressure tip micromanometer and heart morphology was examined. Transmural samples
      of left ventricle were then taken for mRNA quantification of SERCA2a,
      phospholamban (PLB), insulin-like growth factor 1 (IGF-1) and glyceraldehyde-3
      phosphate dehydrogenase (GAPDH). RESULTS: The animals treated with PAN presented
      a decrease in creatinine clearance (14th day: 2.24 +/- 0.32 vs. 4.51 +/- 1.08
      ml/min) and an increase in proteinuria (14th day: 51.0 +/- 9.0 vs. 3.8 +/- 0.7
      mg/mg creatinine), without changes in systolic (14th day: 151 +/- 7 vs. 141 +/- 6
      mmHg) or diastolic blood pressure (14th day: 85 +/- 7 vs. 86 +/- 3 mmHg), These
      alterations were accompanied by cardiac atrophy with decreased left ventricular
      contractility. A reduction in the SERCA2a/PLB mRNA ratio was observed without
      significant alteration in the expression of IGF-1 in the left ventricle.
      CONCLUSIONS: PAN-induced nephropathy is accompanied by cardiac atrophy, left
      ventricular dysfunction and alterations in the expression of genes involved in
      myocardial calcium kinetics. These findings were not accompanied by increases in
      blood pressure and may contribute to our understanding of the increased
      cardiovascular risk in chronic renal insufficiency.

PMID- 16910159
TI  - Treatment of aortic aneurysm with covered stent. Case report.
AB  - The authors present the case of a thirteen-year-old boy with aortic coarctation,
      which was surgically corrected at the age of 2.5 months. He subsequently
      developed recoarctation, which was treated with balloon dilatation. Recently,
      recoarctation and an aortic aneurysm were observed, which were corrected with
      covered stent implantation. We discuss various techniques for correction of
      aortic coarctation, as well as their advantages and disadvantages.

PMID- 16910160
TI  - Acute resynchronization with inhaled iloprost in a pregnant woman with idiopathic
      pulmonary artery hypertension.
AB  - We describe the case of a pregnant woman with idiopathic pulmonary arterial
      hypertension, a responder in right heart catheterization, followed since the
      first trimester in outpatient consultations, admitted to hospital at 23 weeks
      gestation. She was treated with inhaled iloprost until delivery (at 34 weeks
      gestation) and continuous infusion of iloprost throughout the perioperative
      period and following days. This line of therapy has proved efficacious in
      previous cases. The authors present echocardiographic images that document acute
      changes in ventricular synchrony during inhalation of iloprost.

PMID- 16910161
TI  - Ischemic myocardial disease as an example of a thrombotic event. A historical
      note.
AB  - The definition of myocardial ischemia as a clinical entity of thrombotic etiology
      was established in 1912 by James Herrick. His proposal was based on the work of
      William Heberden, who in 1772 defined the clinical profile of angina pectoris,
      and the observations of Edward Jenner about a century later on intracoronary
      thrombosis in patients who had died with such symptoms. On the basis of these
      results, Jenner and Caleb Parry proposed that the main cause of angina were
      alterations in the coronary arteries, while Marshall Hall, in 1842, attributed
      sudden death in these patients to interruption of the coronary circulation. The
      discovery of a common cause for angina pectoris and myocardial infarction,
      inducing a reduction or interruption of oxygen supply to myocardial tissue, the
      atherosclerotic etiology of intracoronary lesions, and the importance of plaque
      fissuring in the sudden formation of intracoronary thrombi, were successive
      milestones in our understanding in the 20th century, the culmination of the
      process of meticulous observation begun many years before.

PMID- 16910162
TI  - Total occlusion of the left main coronary artery in a patient with chronic stable
      angina--case report.

PMID- 16910163
TI  - Savings needed to fund health insurance and health care expenses in retirement.

PMID- 16910164
TI  - Relationship between fatty acids and the endocrine and neuroendocrine system.
AB  - Significant interactions exist between fatty acids and the endocrine system.
      Dietary fatty acids alter both hormone and neuropeptide concentrations and also
      their receptors. In addition, hormones affect the metabolism of fatty acids and
      the fatty acid composition of tissue lipids. The principal hormones involved in
      lipid metabolism are insulin, glucagon, catecholamines, cortisol and growth
      hormone. The concentrations of these hormones are altered in chronic degenerative
      conditions such as diabetes and cardiovascular disease, which in turn leads to
      alterations in tissue lipids. Lipogenesis and lipolysis, which modulate fatty
      acid concentrations in plasma and tissues, are under hormonal control.
      Neuropeptides are also involved in lipid metabolism in brain and other tissues.
      Polyunsaturated fatty acids are also precursors for eicosanoids including
      prostaglandins, leucotrienes, and thromboxanes, which have hormone-like
      activities. Fatty acids in turn affect the endocrine system. Saturated and trans
      fatty acids decrease insulin concentration leading to insulin resistance. In
      contrast, polyunsaturated fatty acids increase plasma insulin concentration and
      decrease insulin resistance. In humans, omega3 polyunsaturated fatty acids alter
      the levels of opioid peptides in plasma. Free fatty acids have been reported to
      inhibit glucagon release. Fatty acids also affect receptors for hormones and
      neuropeptides.

PMID- 16910165
TI  - Role of lifestyle factors on plasma homocysteine levels in Parkison's disease
      patients treated with levodopa.
AB  - Many papers documented that Parkinson's disease (PD) patients treated with
      levodopa (L-dopa) shows elevated plasma homocysteine (Hcy) levels. Several
      lifestyle factors are able to influence plasma Hcy levels. We review the evidence
      that L-dopa therapy is related with an increase in plasma Hcy levels and that
      several behaviours could be able to cause changes in plasma Hcy concentrations.
      Therefore, there are reasons to suggest that a healthy lifestyle lowering Hcy may
      prevent this potential iatrogenic complication during L-dopa therapy. Moreover,
      at present, no controlled prospective studies have evaluated this phenomenon.

PMID- 16910166
TI  - Expression and activity of methionine cycle genes are altered following folate
      and vitamin E deficiency under oxidative challenge: modulation by apolipoprotein
      E-deficiency.
AB  - Folate deficiency increases neuronal oxidative damage and potentiates the
      deleterious effects of apolipoprotein E (ApoE) deficiency. Mice lacking ApoE
      (ApoE -/- mice) upregulate the expression and activity of another enzyme,
      glutathione synthase (GS), when deprived of folate, in an apparent attempt to
      compensate for increased oxidative damage. Herein, we examined the influence of
      ApoE and folate deficiency on expression and activity of several enzymes of the
      methionine cycle. Expression and activity of methylene tetrahydrofolate reductase
      was increased in the order ApoE +/+ < ApoE +/- < ApoE -/- in response to folate
      deprivation. Expression of cystathione beta synthase followed a similar pattern.
      By contrast, expression and activity of methionine synthase decreased following
      folate deprivation in the order ApoE +/+ < ApoE +/- < ApoE -/-. These studies
      demonstrate that folate deficiency induces compensatory regulation of methionine
      cycle genes, and that these effects are potentiated by ApoE deficiency in a gene
      dosage manner. They further support the notion that latent genetic deficiencies,
      including those of methionine cycle, may contribute to Alzheimer's disease,
      especially in concert with age-related nutritional deficiencies.

PMID- 16910167
TI  - Glutamate concentration in whole saliva and taste responses to monosodium
      glutamate in humans.
AB  - It is universally accepted that saliva plays an important role in taste
      sensations. However, interactions between constituents of whole saliva and the
      five basic taste modalities are still poorly understood. The aim of the present
      study was to evaluate possible relationship between endogenous glutamate (Glu)
      levels in whole saliva and taste responses to a prototypic umami substance,
      monosodium glutamate (MSG; 0.03-10.0%). Rated intensity and pleasantness of MSG
      taste was studied in healthy volunteers divided into a high glutamate (HG) in
      saliva (HG; n = 19) and low glutamate in saliva (LG; n = 18) group based on the
      median split level of salivary Glu. The HG and LG group did not differ in terms
      of electrogustometric thresholds, rated intensity of the MSG samples and
      pleasantness of distilled water and the lower MSG concentrations (0.03-1.0%).
      Perceived intensity of water taste was significantly (P < 0.05) higher in the LG
      subjects. The LG group rated the higher MSG concentrations (3.0-10.0%) as more
      unpleasant (P < 0.01). The difference remained significant after controlling for
      a between-group difference in age. The present results suggest that individual
      differences in salivary Glu levels may alter hedonic responses to suprathreshold
      MSG concentrations.

PMID- 16910168
TI  - Ontogenic expression of putative feeding peptides in the rat fetal brain and
      placenta.
AB  - The well-demonstrated "fetal programming" paradigm is based on the observation
      that environmental changes can reset the developmental path and thus, gene
      expression during intrauterine development. As appetite-regulatory neural
      pathways develop in utero, we sought to determine the ontogenic expression of
      putative orexigenic and anorexigenic feeding-regulatory peptides in the fetal rat
      brain and placenta during the last third of gestation. Pregnant Sprague-Dawley
      rats (n = 12) at D14, D16 and D18 were sacrificed and fetal whole brain and
      placenta removed and examined for mRNA levels of orexigenic (neuropeptide Y
      (NPY), agouti-related peptide (AgRP)) and anorexigenic (cocaine and amphetamine
      regulated transcript (CART), pro-opiomelanocortin (POMC)) peptides and leptin
      receptor (OB-Rb) using real-time reverse transcription polymerase chain reactions
      (RT-PCR). For adult comparisons, the hypothalamus, cortex and cerebellum from
      male rats were also examined for feeding peptides. In the fetal brain and
      placenta, mRNA levels of AgRP decreased 10-fold from D14 to D16 and was
      undetectable at D18. Appetite inhibitory factors OB-Rb and CART mRNA levels
      increased from D14 to D18 in the brain and placenta. NPY and POMC expression
      remained unchanged from D14 to D18. The pattern of expression of feeding
      regulatory peptides in the fetal brain most closely resembled the expression
      profile of the adult cerebral cortex. The continued maturation of feeding
      regulatory mechanisms in late gestation indicates the potential for in utero
      programming of ingestive behavior.

PMID- 16910169
TI  - Green tea pain modulating effect in sciatic nerve chronic constriction injury rat
      model.
AB  - We investigated the effect of green tea (GT) in unilateral chronic constriction
      injury (CCI) to the rat scaitic nerve. Five groups (n = 6 rats/group) sham group:
      rats which underwent operation but with no ligation to the scaitic nerve, and
      received tap water for two weeks before and for five weeks after the surgery.
      Four experimental groups underwent CCI to the right sciatic nerve, divided
      randomly as follows: group E were given tap water throughout the study. Group B
      received GT before and after CCI. Group C was given GT following CCI. Group D
      received GT for two weeks prior to CCI. Groups which consumed GT showed
      significant improvement in the toe spread (P < 0.001) and foot positioning (P <
      0.001) tests compared to the experimental control group. In addition, these
      groups showed a significant decrease in the behavioral mechanical hyperalgesia (P
      < 0.0001) and allodynia (P < 0.0002). Consumption of GT improves both reflexes
      and sensation which are often affected in the course of peripheral neuropathy.

PMID- 16910170
TI  - Organization of olfactory glomeruli in neonatally undernourished rats.
AB  - Newborn rats maintain mother-litter bonds by using olfactory signals. At birth,
      units in the olfactory glomeruli (OG) are immature and vulnerable to noxious
      epigenetic factors like undernutrition. Because little is known about the effects
      of neonatal undernutrition upon the OG morphological organization, different OG
      parameters were studied in undernourished Wistar rats at 7, 14 and 21 days of
      age. The issue was addressed by analyzing the olfactory bulb (OB) cross sectional
      area, the total number and area of OGs in the OB coronal sections, and the
      distribution of OG area in dorsal and ventral quadrants. Reductions in the OB and
      OG cross sectional areas were detected at 7 and 14 days posnatally. OG area
      comparisons by OB quadrants were reduced along the study in quadrants, with
      larger effects in medial than in lateral OB quadrants. Current OG
      cytoarchitectonic modifications may affect the newborn capabilities for odour
      discrimination by disrupting early mother-litter interactions.

PMID- 16910171
TI  - Do flavan-3-ols from green tea reach the human brain?
AB  - Following acute ingestion of green tea by six human subjects, HPLC-MS2 analysis
      revealed that flavan-3-ol methyl, glucuronide and sulfate metabolites appeared in
      the bloodstream but did not pass through the blood-cerebrospinal fluid barrier.
      These observations emphasize the discrepancies between in vitro and in vivo
      evidence on the neuroprotective role of these compounds. If, as has been
      proposed, green tea exerts neuroprotective effects, this finding indicates that
      the active components are not flavan-3-ols or their metabolites. Alternatively, a
      systemic action may be hypothesised whereby dietary flavan-3-ols up-regulate
      antioxidant defences and/or reduce inflammation, the benefit of which may be
      effective throughout the body.

PMID- 16910172
TI  - Effects of caffeine in overnight-withdrawn consumers and non-consumers.
AB  - RATIONALE: A number of recent studies have suggested that caffeine only improves
      mood and cognitive performance in regular caffeine consumers who are caffeine
      withdrawn at test (the "withdrawal hypothesis"). This can be tested by
      investigating the effects of caffeine in non-consumers of caffeine. OBJECTIVES:
      To compare the effects of 2 mg/kg caffeine on mood and cognitive performance in
      overnight-withdrawn consumers and non-consumers of caffeine. METHODS: Twenty-five
      overnight-withdrawn consumers and twenty-five non-consumers of caffeine were
      tested in a within-subjects design where they were given a drink containing 2
      mg/kg caffeine on one test day and placebo on another test day. The order of
      conditions (caffeine/placebo) was counterbalanced. Mood and performance measures
      were taken before and after each drink, and pre-drink measures were used as
      covariates in the analysis of post-drink measures. RESULTS: Analysis of baseline
      scores revealed no significant effects of caffeine withdrawal. Caffeine generally
      improved mood and cognitive performance, relative to placebo, in both subjects
      groups. These effects did not differ significantly between groups apart from
      three measures (fewer lapses of attention and ratings of alertness and anxiety)
      where the effects of caffeine were larger in the non-consumers. CONCLUSIONS: The
      present study revealed no negative effects of caffeine withdrawal. Beneficial
      effects of caffeine were observed in both withdrawn consumers and in non
      consumers. Therefore, the withdrawal hypothesis is not an adequate explanation
      for the effects of caffeine.

PMID- 16910173
TI  - Quantitative genetic analysis of brain copper and zinc in BXD recombinant inbred
      mice.
AB  - Copper and zinc are trace nutrients essential for normal brain function, yet an
      excess of these elements can be toxic. It is important therefore that these
      metals be closely regulated. We recently conducted a quantitative trait loci
      (QTL) analysis to identify chromosomal regions in the mouse containing possible
      regulatory genes. The animals came from 15 strains of the BXD/Ty recombinant
      inbred (RI) strain panel and the brain regions analyzed were frontal cortex,
      caudate-putamen, nucleus accumbens and ventral midbrain. Several QTL were
      identified for copper and/or zinc, most notably on chromosomes 1, 8, 16 and 17.
      Genetic correlational analysis also revealed associations between these metals
      and dopamine, cocaine responses, saccharine preference, immune response and
      seizure susceptibility. Notably, the QTL on chromosome 17 is also associated with
      seizure susceptibility and contains the histocompatibility H2 complex. This work
      shows that regulation of zinc and copper is under polygenic influence and is
      intimately related to CNS function. Future work will reveal genes underlying the
      QTL and how they interact with other genes and the environment. More importantly,
      revelation of the genetic underpinnings of copper and zinc brain homeostasis will
      aid our understanding of neurological diseases that are related to copper and
      zinc imbalance.

PMID- 16910174
TI  - The genetic association between alpha-2-macroglobulin (A2M) gene deletion
      polymorphism and low serum A2M concentration in overweight/obese Thais.
AB  - The study subjects were 192 overweight and obese Thais (BMI > 25.00 kg/m2), and
      103 Thai controls (BMI = 18.50-24.99 kg/m2), whose ages ranged from 18-60 years.
      All subjects were evaluated for serum Alpha-2-macroglobulin (A2M), globulin,
      albumin concentration, and polymorphic variation in the A2M gene. Serum A2M and
      albumin were significantly lower in the overweight/obese group (P < 0.05). For
      the overweight/obese and control group, the median ages were 38 and 37 years,
      serum A2M 200.2; 252.0 (mg/L), albumin 4.4; 4.5 (g/dL), and globulin 3.0; 2.95
      (g/dL), respectively. A2M deletion polymorphism genotyping showed no association
      between A2M deletion polymorphism and the two groupings. At serum A2M
      concentration < 250 mg/L, there was no relationship between A2M deletion
      polymorphism and age. Serum A2M had a significant negative correlation with age
      in all subjects (R = 0.09, P < 0.05). The results did not support the hypothesis
      that A2M deletion polymorphism is associated with a low A2M concentration in
      overweight/obese subjects. However, serum A2M had a significant negative
      correlation with age; serum A2M can possibly be used to indicate the aging of
      cells in vivo, including the brain. Further studies are needed to investigate
      other A2M genes located on chromosome 12 to prove A2M gene polymorphism's
      association with low serum A2M and aging.

PMID- 16910175
TI  - A regional model (Northeastern Brazil) of induced mal-nutrition delays ontogeny
      of reflexes and locomotor activity in rats.
AB  - The aim of this study was to investigate the effects of malnutrition, induced by
      a regional basic diet (RBD), on motor development. RBD is a 7.87%-protein diet
      based on aliments typical of Northeastern Brazil, elaborated after nutritional
      investigation by Teodosio et al. (1979). Female rats were treated with RBD during
      lactation. The reflex ontogenesis and the development of locomotor activity in
      their offspring were assessed. Malnourished (MN) rats showed a delay in reflex
      maturation and in locomotor activity evolution. The decreased locomotor activity
      may be related to the reduced movement experiences induced by the delay in the
      reflex maturation. Occurring during the critical period of brain development,
      this fact could jeopardize all the steps in future locomotion evolution. The
      present results confirm deleterious effects of RDB-induced malnutrition on the
      somatic development and maturation of the nervous system (NS).

PMID- 16910177
TI  - Behavioral toxicity of increasing doses of ethanol in malnourished rats.
AB  - In order to verify the toxicity of ethanol in malnourished rats, the following
      procedure was applied to two groups of rats (n = 12 each): group W: drinking
      water ad libitum and group E: drinking only an ethanol solution in a gradual
      dosage (0, 5, 10, 20 and 40% v/v). In the well-nourished phase, all rats received
      food ad libitum (AW and AE). Ethanol treatment (AE) was interrupted for two
      weeks. Rats from both AW and AE groups were submitted to food restriction (50% of
      AW consumption)--malnourished phase (M)--and liquid was offered as described
      before. Signs of ethanol intoxication were recorded daily. Ethanol withdrawal
      symptoms and the open-field test were performed 24 h after the well-nourished and
      malnourished phases. Rats were sacrificed for macroscopic evaluation of liver,
      spleen, thymus and biochemical analyses of the blood (hematocrit, hemoglobin,
      proteins and albumin). Malnourished rats showed more signs of ethanol
      intoxication and withdrawal. In the open-field test, malnourished rats ambulated
      more and made more rearing up. This effect of malnutrition was not observed
      during ethanol withdrawal. Consumption of ethanol decreased the levels of
      hemoglobin, hematocrit and total proteins. Data suggested that toxic profile of
      ethanol was dependent on nutritional status.

PMID- 16910176
TI  - Boron deprivation alters rat behaviour and brain mineral composition differently
      when fish oil instead of safflower oil is the diet fat source.
AB  - PRIMARY OBJECTIVE: To determine whether boron deprivation affects rat behaviour
      and whether behavioural responses to boron deprivation are modified by differing
      amounts of dietary long-chain omega-3 fatty acids. RESEARCH DESIGN: Female rats
      were fed diets containing 0.1 mg (9 micromol)/kg boron in a factorial arrangement
      with dietary variables of supplemental boron at 0 and 3mg (278 micromol)/kg and
      fat sources of 75 g/kg safflower oil or 65 g/kg fish (menhaden) oil plus 10 g/kg
      linoleic acid. After 6 weeks, six females per treatment were bred. Dams and pups
      continued on their respective diets through gestation, lactation and after
      weaning. Between ages 6 and 20 weeks, behavioural tests were performed on 13-15
      male offspring from three dams in each dietary treatment. The rats were
      euthanized at age 21 weeks for the collection of tissues and blood. METHODS AND
      PROCEDURES: At ages 6 and 19 weeks, auditory startle was evaluated with an
      acoustic startle system and avoidance behaviour was evaluated by using an
      elevated plus maze. At ages 7 and 20 weeks, spontaneous behaviour activity was
      evaluated with a photobeam activity system. A brightness discrimination test was
      performed on the rats between age 15 and 16 weeks. Brain mineral composition was
      determined by coupled argon plasma atomic emission spectroscopy. Plasma total
      glutathione was determined by HPLC and total cholesterol and 8-iso-prostaglandin
      F2alpha (8-iso-PGF2alpha) were determined by using commercially available kits.
      MAIN OUTCOMES AND RESULTS: Boron-deficient rats were less active than boron
      adequate rats when fed safflower oil based on reduced number, distance and time
      of horizontal movements, front entries, margin distance and vertical breaks and
      jumps in the spontaneous activity evaluation. Feeding fish oil instead of
      safflower oil attenuated the activity response to boron deprivation. In the plus
      maze evaluation, the behavioural reactivity of the boron-deficient rats fed fish
      oil was noticeably different than the other three treatments. They made more
      entries into both open and closed arms and the center area and thus visited more
      locations. The boron-deficient rats fed fish oil also exhibited the lowest copper
      and zinc and highest boron concentrations in brain and the highest plasma
      glutathione concentration. Both boron deprivation and safflower oil increased
      plasma 8-iso-PGF2alpha. CONCLUSIONS: Both dietary boron and long-chain omega-3
      fatty acids influence rat behaviour and brain composition and the influence of
      one these bioactive substances can be altered by changing the intake of the
      other. Brain mineral and plasma cholesterol, glutathione and 8-iso-PGF2alpha
      findings suggest that rat behaviour is affected by an interaction between boron
      and fish oil because both affect oxidative metabolism and act the cellular
      membrane level.

PMID- 16910179
TI  - Keeping infections under wraps.

PMID- 16910178
TI  - Large ICFs/MR being phased out.

PMID- 16910180
TI  - Sharing the power of life stories.

PMID- 16910181
TI  - Putting A lid on workers' comp.

PMID- 16910182
TI  - Developing a corporate IT strategy.

PMID- 16910184
TI  - Networking from the bottom up.

PMID- 16910183
TI  - Part D: Off to a shaky start.

PMID- 16910185
TI  - Telemedicine's promise: reaching new heights.

PMID- 16910186
TI  - End-of-life decisions made easier.

PMID- 16910187
TI  - FDA unveils food safety update.

PMID- 16910188
TI  - Genetic testing provides clues to better treatment.

PMID- 16910189
TI  - Clocks tell more than time.

PMID- 16910190
TI  - A LEAP toward culture change.

PMID- 16910192
TI  - Medical director's role updated.

PMID- 16910191
TI  - A road map for risk avoidance.

PMID- 16910193
TI  - Yarwood ponders future.

PMID- 16910195
TI  - Better measures, better outcomes.

PMID- 16910194
TI  - Drug plans. Compete for patients.

PMID- 16910196
TI  - Addressing loss-of-weight issues.

PMID- 16910197
TI  - Long term care group draws IT road map.

PMID- 16910198
TI  - Beyond the bedside: what do nurses really do?

PMID- 16910199
TI  - Nursing professionals to be influential part of "Fax Five" campaign.

PMID- 16910200
TI  - Looking beyond the bedside.

PMID- 16910201
TI  - Economic & General Welfare Report: Beyond the bargaining table. Considerations
      for local unit leaders in working with chemically dependent nurses.

PMID- 16910202
TI  - Issues and answers: Physician assistants may now obtain prescriptive authority.

PMID- 16910204
TI  - Clinical and organizational ethics: Ethical dilemmas: challenge and opportunity.

PMID- 16910203
TI  - Health policy report: Yes! We can! Grassroots efforts successful at both the
      federal and state levels.

PMID- 16910206
TI  - The measurement and conceptualization of curiosity.
AB  - In this study, the authors tried various methods to measure and conceptualize
      curiosity. A sample of 369 education students (103 men, 266 women) who were
      attending universities on the East Coast of the United States completed 5 paper
      and-pencil curiosity measures in 1 of their classes. Using confirmatory factor
      analysis, the authors found that the data best fit a 3-factor curiosity model
      consisting of cognitive curiosity, physical thrill seeking, and social thrill
      seeking. These findings supported the development of new instruments that
      specifically measured those 3 curiosity types, new empirical research predicting
      meaningful curiosity-related outcomes, and subsequent theory building concerning
      how and why curiosity is a fundamental part of optimal human functioning.

PMID- 16910207
TI  - Children's understanding of reputations.
AB  - In the present study, the authors investigated age differences in children's
      understanding (a) that a person's behavior may contribute to the formation of a
      shared opinion within the peer group and (b) that origins of a reputation can be
      direct or indirect. The authors read stories in which a target character engaged
      in either prosocial or antisocial interactions with peers to children in
      kindergarten, 2nd, and 4th grade. They then asked the children to judge how
      various peers viewed the target character. Children's explanations indicated that
      children in all of those age groups understood that firsthand experience
      influenced peers' opinions, and by 2nd grade, children understood that indirect
      experience or gossip also might have contributed to an individual's reputation.

PMID- 16910208
TI  - Provider management of child stress behavior in family day care facilities:
      scaffolding for learning and development by developmentally appropriate practice.
AB  - Six children (5 boys, 1 girl; aged 36-60 months) participated in this qualitative
      study. Each child was enrolled in a different family child care facility. The
      authors rated the child care providers in 3 of the facilities as using
      developmentally appropriate practices (DAP) most of the time and rated the
      providers in the 3 other facilities as rarely or never using DAP. They also
      examined provider management of children's stress behaviors. The authors observed
      less active and passive stress behaviors in the high-DAP facilities than in the
      low-DAP facilities. The authors discuss the results with regard to the
      distinctively different day care culture found in high-DAP facilities versus low
      DAP facilities and the implications for practice.

PMID- 16910209
TI  - Prospective memory performance across adolescence.
AB  - In the present study, the authors explored age differences in event-based
      prospective memory (PM) across adolescence. The tasks consisted of an ongoing
      task (OT; i.e., personality questionnaire items, math problems) and an embedded
      prospective task that required participants to remember to make a special
      response whenever they encountered a PM cue (i.e., a negative word in the OT).
      The 341 participants (aged 13-22 years) revealed a significant main effect of
      age, which indicated better PM performance of young adults compared with
      teenagers. Moreover, when emphasizing the OT versus the PM task, teenagers' PM
      profited from PM emphasis more than did young adults' PM. The authors discuss the
      data in the context of limited executive capacity as a factor influencing
      cognitive development across adolescence.

PMID- 16910210
TI  - Loneliness and depression in middle and late childhood: the relationship to
      attachment and parental styles.
AB  - In this study, the author analyzed the relationship between (a) parenting and
      attachment and (b) self-competence, loneliness, and depression in children aged 8
      12 years. The author administered (a) the Argentine Scale of Perception of the
      Relationships with Parents (M. C. Richaud de Minzi, 2004), (b) the Kerns'
      Security Scale (K. A. Kerns, L. Klepac, & A. K. Cole, 1996; M. C. Richaud de
      Minzi, C. Sacchi, & J. E. Moreno, 2001, Argentine adaptation), (c) the Self
      Perception Profile for Children (S. Harter, 1985; M. C. Richaud de Minzi et al.),
      (d) the Dimensions of Depression Profile for Children and Adolescents (S. Harter
      & M. Nowakowski, 1987), and (e) the Louvain Loneliness Scale for Children and
      Adolescents (A. Marcoen, L. Goossens, & P. Caes, 1987; M. C. Richaud de Minzi et
      al.) to 1,019 children (8-12 years of age, 483 boys, 536 girls). Results
      indicated that attachment and parent-child relationship styles were
      differentiated constructs. Parents' acceptance promoted secure attachment and
      positive outcomes in children. Moreover, fathers' lack of interest had a marked
      negative effect. The author found differences in the perceptions and influences
      of fathers and mothers, which follow the cultural patterns of gender attribution.

PMID- 16910211
TI  - Students' perceptions of rewards for academic performance by parents and
      teachers: relations with achievement and motivation in college.
AB  - In the present study, the authors examined college students' (N= 136) perceptions
      of the provision of extrinsic rewards given by parents and teachers for academic
      performance from elementary school through high school. They also examined the
      relations between reward history and present student motivational orientation.
      External rewards for students' grades were common at all levels of schooling.
      Reward history related significantly to students' motivational orientation and
      performance in college, and these relations were generally stronger for boys than
      for girls. The authors discuss implications of these findings.

PMID- 16910212
TI  - Effects of age and ability on self-reported memory functioning and knowledge of
      memory aging.
AB  - The authors examined the effects of age and ability (as measured by education and
      verbal ability) on self-reported memory functioning in adulthood. In Study 1, the
      age and ability groups responded similarly to the Cognitive Failures
      Questionnaire (D. E. Broadbent, P. F. Cooper, P. Fitzgerald, & K. R. Parkes,
      1982), but differences emerged when the authors examined specific items tapping
      prospective and retrospective memory. In Study 2, the authors found age and
      ability differences in self-reported memory functioning, as measured by the
      Memory Functioning Questionnaire (M. J. Gilewski, E. M. Zelinski, & K. W. Schaie,
      1990) and in knowledge of memory aging, as measured by the Knowledge of Memory
      Aging Questionnaire (K. E. Cherry, R. L. West, C. M. Reese, M. P. Santa Maria, &
      M. Yassuda, 2000). In both studies, differences in self-reported functioning were
      not related to objective memory performance. In the second study, knowledge was
      positively related to performance. Implications for conceptions of metamemory and
      memory aging are considered.

PMID- 16910213
TI  - Mental energy: Defining the science.

PMID- 16910214
TI  - Mental energy: Developing a model for examining nutrition-related claims.

PMID- 16910215
TI  - Mental energy: Assessing the mood dimension.
AB  - Conceptualizing mental energy as a mood is impor tant, because these feelings are
      important to people and can influence behavior in the real world. If a person
      feels a lack of energy, for example, he or she is more likely to avoid physical
      or mental work if it is possible to do so. Alternatively, this person may seek to
      improve feelings of energy by eating, drinking, taking dietary supplements or
      drugs, sleeping, or engaging in other behaviors. Thus, the measurement of the
      mood of energy has importance in numerous ways, including public health, work
      productivity, and ultimately economic growth and productivity. Mood data have
      limitations, for example, self aware ness and literacy are necessary and faking
      is possible. The problem of faking is most salient in situations in which there
      is a strong motivation to fake, such as when psychological testing is used as
      part of an employment application. Despite these limitations, overwhelming
      evidence supports the validity for certain measures of the mood of energy such as
      the POMS vigor scale. This is not to say that mood measures are error free in all
      situations. Despite some error, however, validity evidence for mood measures is
      published in the scientific literature weekly. Future research aimed at
      determining the biological bases for the mood of energy, and its relationships to
      overlapping phenomena such as cognitive fatigue, should yield results that
      ultimately help us to understand how to optimize our feelings of energy.

PMID- 16910216
TI  - Mental energy: Assessing the cognition dimension.
AB  - The cognitive dimension of mental energy can be assessed by tests of vigilance
      and choice reaction time. These behaviors are relatively simple cognitive
      functions and can be measured with precision and reliability if carefully
      designed and implemented tests are used. Because the concept of mental energy is
      still evolving, the selection of appropriate tests to assess it must be
      tentative. However, vigilance and choice reaction time seem to have the necessary
      psychometric properties for assessing mental energy, including construct,
      predictive content, and face validity. Tests of reaction time and vigilance are
      correlated with questionnaires that measure mood states corresponding to mental
      energy--such as sleepiness, fatigue, and alertness--in the expected manner and
      are of approximately equivalent sensitivity.

PMID- 16910217
TI  - Mental energy: Assessing the motivation dimension.
AB  - Content-based theories of motivation may best uti lize the meta-theory of work
      motivation. Process-based theories may benefit most from adopting Locke and
      Latham's goal-setting approaches and measures. Decision-making theories should
      utilize the measurement approach operationalized by Ilgen et al. Sustained effort
      theories should utilize similar approaches to those used in numerous studies of
      intrinsic motivation, but the measurement of which is typically observational or
      attitudinal. This paper explored the implications of the four approaches to
      studying motivation on the newly estab ished model of mental energy. The approach
      taken for examining motivation informs the measurement of mental energy. Specific
      recommendations for each approach were developed and provided. As a result of
      these efforts, it will now be possible to diagnose, measure, and experimentally
      test for changes in human motivation, which is one of the three major components
      of mental energy.

PMID- 16910219
TI  - The Recommended Dietary Allowance (RDA) should not be abandoned: an individual is
      both an individual and a member of a group.

PMID- 16910218
TI  - Dietary therapy in idiopathic nephrolithiasis.
AB  - Like other diseases striking predominantly the affluent societies, idiopathic
      nephrolithiasis is increasing in rich countries and appears to be closely related
      to dietary habits. In this review we summarize the latest evidence about the
      efficacy of dietary treatment for idiopathic calcium and uric acid stones,
      dealing especially with its effect on the urinary stone risk factors, stone
      recurrences, and clinical limitations. After a short introduction on epidemiology
      and pathogenesis, we review the role of the most important foods and nutrients in
      stone formation and protection: water and other fluids, proteins, carbohydrates,
      fats, salt, milk and dairy products, fruits and vegetables, and vitamins. The
      final part of the paper will provide practical guidelines for pursuing an anti
      lithogenic diet in idiopathic calcium and uric acid stones.

PMID- 16910220
TI  - Underreporting of energy intake in developing nations.
AB  - Under conditions of energy balance, energy intake (EI) equals energy expenditure
      (EE), and the validity of EI may be determined by comparing these two measures.
      The doubly labeled water (DLW) method is the gold standard for the determination
      of EE. Its use in developed countries has showed an intense underreporting of EI.
      Few studies concerning underreporting have been conducted in developing nations,
      and none of them has used DLW. This review will present the results of such
      studies, extrapolating data using DLW and providing EE and EI estimates, but
      which were not concerned with underreporting. A panorama of underreporting and
      its implications in developing nations is discussed and future directions for
      research are identified.

PMID- 16910221
TI  - Bitter gourd (Momordica Charantia): A dietary approach to hyperglycemia.
AB  - Bitter gourd (Momordica charantia) is a vegetable with pantropical distribution.
      It contains substances with antidiabetic properties such as charantin, vicine,
      and polypeptide-p, as well as other unspecific bioactive components such as
      antioxidants. Metabolic and hypoglycemic effects of bitter gourd extracts have
      been demonstrated in cell culture, animal, and human studies. The mechanism of
      action, whether it is via regulation of insulin release or altered glucose
      metabolism and its insulin-like effect, is still under debate. Adverse effects
      are also known. Nevertheless, bitter gourd has the potential to become a
      component of the diet or a dietary supplement for diabetic and prediabetic
      patients. Well-designed interdisciplinary research by nutritionists, medical
      doctors, and agronomists is needed before a dietary recommendation can be given
      and a product brought to the market.

PMID- 16910222
TI  - Nutritional aspects of breath testing based on stable isotopes.
AB  - Stable isotope methodologies offer a number of possibilities for the nutritional
      assessment of many different processes and metabolic pathways. The application of
      stable isotopes has been boosted by the development of new mass spectrometers,
      lower costs of probes, and the risks associated with radioactive tracers. The use
      of 13C as a tracer offers all the advantages of stable isotopes and has been
      widely applied for measuring various types of metabolic processes. This review is
      focused on clinical and nutritional assessments using 13C breath tests.

PMID- 16910223
TI  - The role of dietary supplementation with plant sterols and stanols in the
      prevention of cardiovascular disease.
AB  - Several studies have shown that increased levels of low-density lipoprotein (LDL)
      cholesterol predict cardiovascular events. The Adult Treatment Panel II (ATP II)
      introduced the principle of therapeutic lifestyle changes, including plant
      sterols/stanols for the management of LDL cholesterol. Plant sterols and stanols
      in fat matrices effectively lower LDL cholesterol levels in hypercholesterolemic,
      diabetic, and healthy human volunteers. Recent studies also show that sterols (2
      g/d) lower LDL cholesterol even when incorporated in nonfat matrices. In
      addition, they may reduce biomarkers of oxidative stress and inflammation. Plant
      sterols and stanols exert their hypocholesterolemic effects possibly by
      interfering with the uptake of both dietary and biliary cholesterol from the
      intestinal tract. Present evidence is accumulating to promote their use for
      lowering LDL cholesterol levels, as a first line of therapy (as well as
      adjunctive therapy) in patients on statin therapy.

PMID- 16910224
TI  - Venous thromboembolism: risk assessment, prevention could save lives.

PMID- 16910225
TI  - AMS annual meeting feature sessions: politics and policy talk.

PMID- 16910226
TI  - Trends in healthcare payment.

PMID- 16910227
TI  - NCA and BOR consider new credentialing agency.

PMID- 16910228
TI  - Validating the assessment of Glucose-6-Phosphate dehydrogenase (G6PD).

PMID- 16910229
TI  - Clinical laboratory science: A profession with honors.
AB  - Texas Tech University Health Science Center (TTUHSC) supports a strong
      undergraduate honors program. Students are required to enter the Honors College
      as freshmen and enroll in at least 24 hours of honors-designated classes. Some of
      the clinical core courses in the clinical laboratory science (CLS) program are
      designated as honors courses so students can continue their contract agreement
      with the Honors College to enroll in at least six hours of honors credit at the
      junior and senior level. By providing further educational experiences out of
      class, these honors students are able to meet the requirements needed to graduate
      with highest honors. A CLS honors program not only benefits the student but also
      the faculty involved and the program curriculum.

PMID- 16910230
TI  - Antiphospholipid syndrome: an overview.
AB  - This paper reviews antiphospholipid syndrome (APS), also known as Hughes
      syndrome, which is a potentially life-threatening autoimmune disorder where the
      body produces antibodies directed toward phospholipids and phospholipid-binding
      proteins. Diagnosis of this syndrome relies on both clinical and laboratory
      criteria. Laboratory testing used for diagnosing APS includes coagulation assays
      for the detection of lupus anticoagulant (LA) and enzyme-linked immunosorbent
      assay (ELISA) for antiphospholipid antibody (APL) detection.

PMID- 16910231
TI  - Training technologists for the genomic age.
AB  - Molecular techniques are playing an ever-increasing role in all areas of anatomic
      and clinical pathology. The field is currently in need of well-trained
      technologists in this area of the clinical laboratory who are situated to bridge
      the current state of practice and the continuing developments in high complexity
      testing. For the close term, use of "home-brew" and analyte specific reagents
      (ASR)-based tests will require well-trained personnel with strong biomedical
      science backgrounds and a thorough understanding of technologies used in assay
      development. Here, we discuss the selection and evaluation of molecular
      diagnostic training preceptor sites and tasks indicated for trainees that most
      meet the needs of the newest facet of the laboratory. We present evaluation tools
      developed over the course of four years of clinical education used to assess
      practical performance of trainees in a molecular diagnostic pathology laboratory
      and conclude with considerations for future training of laboratory technologists.

PMID- 16910232
TI  - Down syndrome with myelodysplasia of megakaryoblastic lineage.
AB  - The association between Down syndrome and acute myelogenous leukemia (AML) has
      been well documented. AML in Down syndrome is usually a specific type of
      megakaryoblastic leukemia (M7, AMKL). A myelodysplastic syndrome generally
      precedes this malignancy. Down syndrome patients with AMKL have a much better
      prognosis than other children with AML. A case study of a 22-month-old female
      with Down syndrome and myelodysplastic syndrome of a megakaryoblastic lineage is
      presented here. Upon admission to a pediatric hematology/oncology clinic, flow
      cytometry results reported a distinct population of phenotypically abnormal
      myeloblasts expressing myeloid antigens and the immature cell markers. The
      patient was placed on a national research group study and began chemotherapy
      treatment. To date she has received two courses of cytarabine (ara-c) and
      daunorubicin therapy, which were tolerated well, and is awaiting her third
      course. Her blood counts stabilize for a while after treatments and her prognosis
      is good.

PMID- 16910233
TI  - Co-inheritance of alpha and beta-thalassemia in a Jordanian family.
AB  - Additional alpha-genes may increase the severity of heterozygous beta
      thalassemia. Conversely, the co-inheritance of alpha-thalassemia with homozygous
      beta-thalassemia and the consequent reduction in alpha-globin chain excess often
      results in a milder clinical and haematological phenotype. This study describes
      the hematological and the molecular data resulting from the interaction between
      alpha and beta-thalassemia determinants in a Jordanian family. The parents are
      double heterozygotes for alpha and beta-thalassemia. DNA analysis of four
      children characterized homozygosity for beta+ IVS 1.6 thalassemia mutation in
      three of them. Co-existing heterozygosity for -alpha 3.7 was detected in two of
      them (Children 1 and 2). Those two children have a less severe clinical course
      than that of the third child (Child 3) with homozygosity for beta-thalassemia
      only. The co-existence of -alpha3.7 mutations with homozygous beta-thalassemia
      may have converted a transfusion-dependent thalassemia major to non transfusion
      dependent thalassemia intermedia. The fourth child (Child 4) was heterozygous for
      -alpha3.7 but lacked beta+ IVS 1.6 mutation and appeared normal.

PMID- 16910234
TI  - A model for educational enrichment and employment recruitment for clinical
      laboratory science students.
AB  - An educational partnership was initiated between a pharmaceutical company and a
      university-based clinical laboratory science program to achieve mutually
      beneficial objectives. This external enrichment site provides a unique
      educational experience for the students that cannot be duplicated any where else
      in the community. The framework for the educational experience was established
      with a full day's schedule of visits and presentations guided by a list of twenty
      learning objectives. Clinical laboratory science students interact with
      laboratory professionals who are employed by the pharmaceutical company and
      assigned to a variety of traditional and non-traditional roles. During the visit,
      pharmaceutical company employees observe student interactions in small group
      settings and assess the learners' interest in the work environment and specimen
      testing process. Employee feedback may be applied to future employment decision
      making. This article describes how employer outreach goals and initiatives and
      educational enrichment objectives can be met through cooperative team work.

PMID- 16910235
TI  - Searching for hereditary hemochromatosis.
AB  - OBJECTIVE: To detect hereditary hemochromatosis (HH) in low-income residents of a
      medically underserved region through free screening and confirmatory laboratory
      testing and to raise awareness of HH in the general population. DESIGN: Two
      tiered reflexive laboratory testing was used to screen for HH. Participants
      evaluated the project by written survey upon its conclusion. Data were analyzed
      by descriptive techniques. SETTING: Local public health departments in 18
      counties in western North Carolina (WNC). PARTICIPANTS/SUBJECTS: Phase 1: adult
      volunteers age > or = 20 without previous diagnosis of HH; Phase 2: Phase 1
      participants with elevated screening results and adult family members of Phase 2
      participants found to have HFE mutations; Phase 3: randomly-selected Phase 1
      participants (Survey A) and all Phase 2 participants with HFE mutations (Survey
      B). INTERVENTIONS: Phase 1 (initial screening): non-fasting blood collection by
      venipuncture with testing for transferrin saturation (TS). Phase 2 (confirmatory
      testing): fasting blood collection by venipuncture for TS, serum ferritin (SF),
      and cheek swab for DNA analysis for two HFE mutations (C282Y and H63D). Phase 3:
      written Surveys A and B. MAIN OUTCOME MEASURES: Total number participants
      screened for HH; prevalence of elevated TS in Phase 1 participants; prevalence of
      HFE genotypes consistent with HH (C282Y/C282Y and C282Y/H63D) in Phase 2
      participants; prevalence of elevated SF in subjects with HFE mutations; number of
      family members tested; number of participants being treated for HH as a result of
      screening; increase in awareness of HH among Phase 1 participants. RESULTS: 2,034
      total subjects participated in screening events and/or family member testing. Of
      the 1,976 Phase 1 participants, 130 (6.6%) had elevated TS (> or = 45%). Twenty
      of 130 (15.4%) Phase 2 subjects were homozygotes for C282Y. The prevalence of the
      C282Y/C282Y genotype among the Phase 1 participants who were tested in Phase 2
      was 20/1976 (1.0%). Fourteen of 20 (70%) C282Y homozygotes had elevated SE Eleven
      of 130 (8.5%) Phase 2 subjects were compound heterozygotes for C282Y and H63D,
      and none had elevated SE Of 58 family members tested, two (3.4%) were homozygotes
      for C282Y and eight (13.8%) were compound heterozygotes for C282Y and H63D. One
      of two (50%) family members homozygous for C282Y had an elevated SE No compound
      heterozygotes had elevated SE Sixty-four of 120 (54.2%) Phase 1 subjects
      responded to Survey A. 53.1% of respondents were unaware of HH prior to the
      screening event. 92.1% of respondents told their family and friends about HH
      after participating. 73.4% discussed their laboratory results with their
      healthcare provider. Twenty of 41 participants (48.8%) found to have HFE
      mutations associated with HH responded to Survey B. Eleven of 20 (55.0%) stated
      that they were being treated for HH. CONCLUSION: The prevalence of the major
      genetic mutation, C282Y/C282Y, associated with HH among Phase 1 study
      participants in WNC was 1%, more than three times the national prevalence of
      approximately 0.33%. Results suggest that free screening using laboratory tests
      in a two-tiered reflexive approach may be an effective means of detecting HH,
      especially in high-risk populations. Early detection through free laboratory
      screening tests may reduce morbidity and, ultimately, healthcare costs for low
      income individuals. Awareness of HH as a health concern may increase as a result
      of publicity generated by screening events.

PMID- 16910236
TI  - Learning objects: resources for instruction.
AB  - OBJECTIVE: Upon completion of this article, the reader will be able to describe
      learning objects (LOs) and discuss their use in clinical laboratory sciences
      instruction. DESIGN: Through a questionnaire, educators evaluated clinical
      laboratory sciences-related LOs for accessibility, usability and instructional
      qualities. SETTING: LOs were presented on a password-accessed website.
      Evaluations were completed on the website. PARTICIPANTS: Nine educators
      participated in the evaluation. INTERVENTIONS: The LOs were made available to
      participants for use in their own instructional material. MAIN OUTCOME
      MEASURE(S): The evaluation measured educators' interest in and perceived
      usefulness of LOs in clinical laboratory sciences curriculum. RESULTS: On a scale
      of one to five with one equal to poor and five equal to excellent, participants
      rated LOs as accessible (4.68) and usable (4.61). Ninety-eight percent stated
      that they would use LOs in their curriculum. Fifty-seven percent stated that they
      could attribute improved learning performance on student exposure to LOs.
      CONCLUSION: LOs are useful, relevant, and time-saving resources to clinical
      laboratory sciences instruction.

PMID- 16910237
TI  - Teaching and assessing new method verification skills using interactive
      simulations.

PMID- 16910238
TI  - The impact of schools self-administering substance abuse surveys: an evaluation.
AB  - The literature suggests that administering drug surveys to public school students
      is best done by persons outside of the school system (or at least unfamiliar to
      the students). This is the approach used by the long-time Monitoring the Future
      project. Because of the increased costs that administration by outside research
      associates requires (both time and transportation), we decided to design an
      experiment that would compare it to administration by school personnel. Six
      school systems were split, and 3756 surveys were administered, about half by
      outside research associates and half by school personnel. The results indicate
      that there were minimal and non-significant differences between the two groups.
      On the basis of these results, we draw the conclusion that school personnel are
      able to administer survey instruments without affecting the quality of the
      results and, thus, that school districts may safely use such data in the
      evaluation of their drug education and drug prevention programs.

PMID- 16910239
TI  - Using diaries to assess nonprescription drug use among university students.
AB  - Nonprescription drug use among university students was investigated using survey
      and behavioral diary methodologies to assess usage of nonprescription drug use
      and to compare survey and diary methodologies. Surveys were completed by 183
      students (136 females and 47 males) that asked how often they used
      nonprescription drugs and what those drugs were. Of these participants, 61 (53
      females and 8 males) voluntarily completed behavioral diaries for nonprescription
      drug use for a three week period. Survey data showed 83.1% of participants used
      nonprescription drugs in the past week, with pain relievers being the most common
      drug used. There was a significant correlation between the number of times
      participants reported using nonprescription drugs on the surveys and what the
      participants reported in their diaries, with no differences in the mean number of
      uses between survey and diary. This indicates that participants can recall
      information about their medication-taking behavior with some accuracy. Behavioral
      diaries were also able to show some of the misuse that is associated with using
      nonprescription medications. In most cases of misuse, too large a dose was taken.
      Students should be provided with information about the possible long- and short
      term effects of these medications.

PMID- 16910240
TI  - Youth tobacco sales-to-minors and possession-use-purchase laws: a public health
      controversy.
AB  - Tobacco use among youth remains one of our nation's most significant public
      health problems, and yet available evidence from prevention and cessation person
      centered approaches has been mixed. Given these disappointing outcomes, some have
      recommended more public health approaches, and these include tobacco sales-to
      minors and possession-use-purchase laws. While community members and police
      officials have endorsed these types of public health initiatives, many within the
      public health community have been either guarded or even oppositional to such
      approaches. The primary reasons for this controversy are reviewed in this
      article. Outcome studies indicate that sales-to-minors laws can be an effective
      step toward the reduction of youth access to commercial sources of tobacco.
      However, even with these laws in place, many youth indicate that they continue to
      have easy access to tobacco, often by means of social sources. Advocates of these
      approaches have argued that more comprehensive public health interventions are
      needed, such as programs that combine youth access and possession-use-purchase
      laws. This article reviews the ongoing debate behind these types of public health
      efforts, and examines the evidence of such programs to reduce youth tobacco use.

PMID- 16910241
TI  - Perceptions of drinking among Hispanic college students: how qualitative research
      can inform the development of collegiate alcohol abuse prevention programs.
AB  - Alcohol abuse on college campuses continues to be a significant public health
      issue and health promotion strategies are being directed at changing the culture
      of collegiate drinking. From a qualitative research perspective such efforts
      remain uniformed since this area of research is currently dominated by large
      scale surveys that illuminate little regarding undergraduate perceptions of
      alcohol use. This study describes results conducted on perceptions of drinking
      among college students, and discusses the implications these results may have for
      developing collegiate alcohol abuse prevention programs.

PMID- 16910243
TI  - Dr Shiver's horrendous experience with a patient.

PMID- 16910242
TI  - An evaluation of the fidelity of implementation of a school-based drug abuse
      prevention program: project toward no drug abuse (TND).
AB  - This article provides an implementation fidelity evaluation of the fourth
      experimental trial of Project Towards No Drug Abuse (TND). Two theoretical
      content components of the curriculum were examined to increase our understanding
      of the active ingredients of successful drug abuse prevention programs. A total
      of 18 senior high schools were randomly assigned by block to receive one of three
      conditions: cognitive perception information curriculum, cognitive perception
      information + behavioral skills curriculum, or standard care (control). These
      curricula were delivered to both regular and continuation high schools students
      (n=2331) by trained project health educators and regular classroom teachers.
      Across all program schools, the two different curricula were implemented as
      intended, were received favorably by students, and showed significant
      improvements in knowledge specific to the theoretical content being delivered.
      This pattern of results suggests that the experimental manipulations worked as
      intended, and thus, permit the attribution of future behavioral outcome
      differences between conditions to differences in content of Project TND material
      provided rather than to differences in the fidelity of delivery. Further, our
      findings indicate that Project TND can be implemented effectively with low and
      high risk youth in a general environment as well as with high risk youth in a
      more specialized environment.

PMID- 16910244
TI  - Profile: Mark Duncan, DDS.

PMID- 16910245
TI  - Reminiscences of an early dental practitioner in western Oklahoma. 1941.

PMID- 16910246
TI  - The five questions dentists should ask about their money and why.

PMID- 16910247
TI  - Campaign for fragrance free health care in the U.S.

PMID- 16910248
TI  - Reforming the inpatient PPS system.

PMID- 16910249
TI  - [Ecology of medical care, the square of White, primary care and general
      practice].
AB  - The White-Williams-Greenberg diagram, also called the square of White,
      illustrates the repartition of health care as it was assessed in the sixties
      based on US and UK observations. The concept of the ecology of medical care led
      to passionate debates. The present article aims at reviewing the history of the
      square of White and of its successive adaptations. It will focus on its influence
      in various fields, such as research in primary care, general practice and
      teaching of medicine.

PMID- 16910250
TI  - [Family practitioner and carbon monoxide poisoning].
AB  - Carbon monoxide poisoning is not easily identifiable. It is the first cause of
      death by accidental poisoning in Europe. The family practitioner, who has not
      been made aware of this problem, incurs the risk of diagnostic indecision or of
      involuntary personal poisoning. Since symptomatology is non specific, the general
      practitioner answering housecalls is sometimes confronted with an urgent medical
      problem linked to the complications of this intoxication (coronary, neurological
      problems...), without having ways of documenting its origin of the poisoning or
      any means to protect himself. Through direct contact with his patients'
      environment, the family practitioner, being made sensitive to this problem, can
      certainly contribute to care and aftercare of the patient suffering from carbon
      monoxide poisoning, but also to the prevention of this public health problem
      often called "the silent killer".

PMID- 16910251
TI  - [Value of bone densitometry for the diagnosis and monitoring of osteoporotic
      patients: integration with biological and clinical risk factors].
AB  - The diagnosis of osteoporosis and the monitoring of antiosteoporosis therapies
      imply a better and more rational use of bone densitometry. The optimal
      prescription modalities of this fundamental examination are favorably correlated
      with the efficacy of modern therapeutics. The rationale of this article is to
      provide the general practitioner with a factual update on the diagnostic and
      prognostic use of bone densitometry.

PMID- 16910252
TI  - [Tympanometry in children in general practice].
AB  - Accurate diagnosis of otitis media in children is essential but sometimes
      difficult. Good knowledge of signs and symptoms of acute otitis media and otitis
      media with effusion is not always sufficient. Tympanometry is an easy
      investigation that can be useful in general practice. Here is a review of the
      principle and the limitation of that technique.

PMID- 16910253
TI  - [Rapid antigen tests in acute pharyngitis].
AB  - Acute pharyngitis is one of the most common illnesses for which adults seek
      medical help from primary care physicians. Approximately 15% of cases in adults
      are caused by group A beta-hemolytic Streptococcus. Strategies of management
      should aim at identifying the latter with a view to prevent the development of
      complications. Rapid Antigen tests have a reported specificity of more than 95%.
      Antibiotic therapy is only recommanded for patients with positive rapid antigen
      test results and those with risk factors.

PMID- 16910254
TI  - [Thyroid nodules].
AB  - Thyroid nodules are commonly encountered in clinical practice. They are present
      in 4 to 7% of the population by neck palpation and 30 to 50% by ultrasonography.
      Most are benign and could be neglected by the clinician and his patient. However,
      5% of nodules are malignant, requiring surgical treatment; therefore, an
      exhaustive evaluation is needed. The diagnostic approach includes physical
      examination, laboratory analysis, ultrasonography, radioisotope imaging, and fine
      needle aspiration. This article, based on the literature and the
      authors'experience, provides recommandations for thyroid nodule management.

PMID- 16910255
TI  - [Herpesvirus 6. What attention does it deserve in general practice?].
AB  - The human herpesvirus 6 (HHV6) is a member of the beta-herpes viridae family. The
      primary infection is usually asymptomatic and commonly occurs during childhood.
      The clinical form is called exanthema subitum, or roseala infantum or the 6th
      disease. This biphasic disorder usually runs a benign course and requires no
      antiviral treatment. However, the HHV6 reactivation can lead to serious systemic
      diseases, especially encephalopathy, that may be fatal in the immunocompromised
      or grafted patient. In seronegative pregnant women, a primary HHV6 infection
      contracted from a child with roseola infantum can lead, in rare instances, to
      spontaneous abortion during the first trimester, or produce neurological
      complications in the newborn after HHV6 transplacental infection. Aciclovir,
      ganciclovir (GCV), foscarnet and cidofovir show anti-HHV6 in vitro efficacy, but
      GCV is currently the first line agent when of HHV6 infection is diagnosed in the
      immunocompromised patient.

PMID- 16910256
TI  - [A review about nephropathia epidemica].
AB  - We propose a review of history, aetiology, physiopathology, clinical features,
      treatment and prevention of nephropathia epidemica (NE) which represents the only
      form of Hantavirus infection in Belgium.

PMID- 16910258
TI  - [Psoriasis and psoriatic arthritis].
AB  - Psoriasis is a frequent multifactorial chronic skin disease that can lead to a
      decreased quality of life. Some patients also present arthritis. Those two
      complex inflammatory diseases share some of their characteristics, but several
      clinical manifestations can be distinguished in each of them. In addition to
      classical medications (constituted of topical treatments, methotrexate,
      ciclosporin and retinoids for cutaneous psoriasis and non steroidal anti
      inflammatory drugs or methotrexate for psoriatic arthritis), they are the target
      of a new generation of therapies: the biologics.

PMID- 16910257
TI  - [Management of hyperferritinemia].
AB  - Hemochromatosis is the most common genetic disorder in persons of northern
      European descent, and the majority of cases are caused by a mutation in the gene
      HFE. Genetic testing for hemochromatosis is therefore indicated in all patients
      with increases in transferrine saturation and ferritin levels. When this genetic
      testing does not demonstrate a hemochromatosis, other diseases responsible for
      elevated ferritin levels have to be ruled out, mainly hemolytic anemia, chronic
      inflammatory disorders, liver diseases such as hepatitis B or C, alcohol abuse,
      and non alcoholic fatty liver disease. In demonstrated iron overload with absence
      of classic causes, second-line genetic testing should be considered.

PMID- 16910259
TI  - [Extracorporeal shock wave therapy value in calcific soft tissue pathologies].
AB  - Extracorporeal Shock Wave Therapy (ESWT) regularly used in Urology finds at
      present an indication for the treatment of soft tissue calcifications. A
      literature review presents the physical characteristics, action mode and side
      effects; it also outlines some of the clinical indications.

PMID- 16910260
TI  - [The "footscan" in sport medicine].
AB  - Clinical examination of the foot in a patient or sportsman requires a detailed
      analysis of walking (and running). Current technology allows to study temporal
      fluctuations of plantar pressures and to detect the anomalies responsible for
      sport specific pathologies or pathologies encountered in sick predisposed people.

PMID- 16910261
TI  - [Should general practitioners be interested in homocysteine measurements?].
AB  - The role of hyperhomocysteinemia as a cardiovascular risk factor has been a
      matter of debate of several decades. The present paper briefly describes the
      metabolism of homocysteine, the main genetic and acquired causes of
      hyperhomocysteinemia and the mechanisms presumably involved in the pathogenesis
      of cardiovascular and thromboembolic diseases. Current evidence-based data from
      epidemiological and interventional studies assessing the potential role of
      hyperhomocysteinemia in the occurrence of vascular complications are presented.
      Guidelines on screening and treatment of hyperhomocysteinemia are analysed in the
      context of daily practice of general practitioners.

PMID- 16910262
TI  - [Patent foramen ovale and migraine, a fortuitus association or a causal
      relationship?].
AB  - Epidemiologic studies have shown a clear comorbidity between migraine with aura
      and a patent foramen ovale (PFO). Under the age of 55, migraine with aura is a
      risk factor for ischemic stroke and a proportion of the latter is due to a PFO.
      It remains to be determined whether PFO is causally related to migraine attacks,
      or is a fortuitous association due to common genetic factors. Cortical spreading
      depression which is the underlying mechanism of the migrainous aura, could be
      favoured by a PFO. Several retrospective and uncontrolled studies suggest that
      percutaneous closure of a PFO for stroke or decompression illness in divers
      reduces frequency of migraine attacks with, but also without aura. Multicentric,
      prospective and controlled trials of this intervention in migraineurs are
      underway or in preparation. As long as their results are not known, there is no
      rationale for proposing PFO closure for migraine.

PMID- 16910263
TI  - [Recommended approach towards a fortuitously diagnosed cardiac arrhythmia].
AB  - In the present article, we elaborate a rational approach for the initial
      management of arrhythmias by the general practitioner. We briefly review the
      electrocardiographic aspects of arrhythmias.

PMID- 16910264
TI  - [How to manage chronically low blood pressure?].
AB  - Chronic arterial hypotension has been poorly studied. Its mechanisms are not well
      understood; its treatment (if needed) is disappointing, without any demonstrated
      improvement of symptoms or prognosis. Thus, a complete medical examination is
      needed to exclude any organic cause. If none is found, it is important to
      reassure the patient and to convince him not to use expensive drugs potentially
      generative of side effects.

PMID- 16910265
TI  - [Secondary prevention after a myocardial infarction].
AB  - Patients after a myocardial infarction are at increased risk of adverse
      cardiovascular outcomes. They require aggressive secondary preventive measures to
      control cardiovascular risk factors, and prescription of some pharmacological
      agents. Compelling data derived from randomized controlled trials have shown the
      benefits of aspirin (or clopidogrel), statins, beta-blockers and angiotensin
      converting enzyme inhibitors, in preventing recurrent events and improving
      survival. In some cases oral anticoagulants or fibrates may be necessary. Other
      agents as antioxidant vitamins, folate and B vitamins are disappointing.
      Lifestyle and dietary modifications can also have an important beneficial effect
      on mortality rates and should never be neglected.

PMID- 16910267
TI  - [Smoking experimentation in adolescents. Is there a risk for health?].
AB  - It is clear that even low rate smoking is hazardous for health, the risk being
      independently increased by the daily number of cigarettes smoked and by the
      duration of smoking. The question raised is thus: will an adolescent experimenter
      be a non smoker, an experimenter for ever, a regular smoker, light or heavy? This
      short review shows that there are numerous factors from genetics, to familial
      environment not limited to tobacco issues, smoking situation at school as well as
      school performances of the student, and also individual psychological
      characteristics. The experimenter is a very good target for smoking cessation
      actions and should deserve particular attention from preventive medicine and,
      thus, from school medicine, before he becomes a regular smoker, who will be more
      resistant to smoking cessation programs.

PMID- 16910266
TI  - [Do statins have a place for cardiovascular prevention in elderly people?].
AB  - Cardiovascular prevention should only be considered if the treatment reduces the
      incidence of coronary and cerebrovascular events and death. In elderly people,
      such treatment should also, and most importantly, help maintain a good quality of
      life, without increasing the risk of iatrogenic side-effects. These key-elements
      should be kept in mind when prescription of a statin is envisaged in the old (>
      70 years) and especially the very old (> 80 years) individual. Randomised
      controlled trials in people above 70 years are rather rare. In the field of
      cardiovascular prevention, two studies provide information, on post-hoc analysis
      of the Heart Protection Study (HPS) with simvastatin and the PROSPER trial with
      pravastatin. The protection observed in the general population of HPS was also
      present in the subgroup of subjects aged above 70, both for coronary and
      cardiovascular events. The difference was less impressive in PROSPER, without any
      significant difference as far as the incidence of stroke was concerned. None of
      these two prospective trials provide specific data on individuals above 80.
      Interestingly, some experimental and epidemiological observations suggested that
      statins may prevent Alzheimer disease. However, the data from HPS and PROSPER are
      not convincing in this respect. Thus, results from new ongoing trials should be
      awaited, especially in patients with mild to moderate Alzheimer disease. Finally,
      it is noteworthy that low serum cholesterol level can be used as a marker of poor
      nutrition in very old people. Such condition is rather common, especially among
      institutionalised subjects, and is usually associated with a higher risk of
      morbidity and mortality.

PMID- 16910268
TI  - [Long-term oxygen therapy in chronic obstructive pulmonary disease].
AB  - Ambulatory oxygen therapy has become standard care for chronic hypoxemia. Indeed,
      two large multicenter trials have clearly shown the survival benefit from long
      term home oxygen therapy. We present the rationale for using ambulatory oxygen
      therapy and the different home oxygen systems.

PMID- 16910269
TI  - [Management of mild and moderate forms of chronic kidney disease].
AB  - The prevalence of chronic renal insufficiency, the cost related to its presence
      and the associated high cardiovascular risk are increasing. Early detection is
      needed, with, in parallel, identification of all frequently associated
      cardiovascular risk factors. The general practitioner here plays a major role.
      Sometimes, a first reference to the nephrologist is requested, for instance in
      the presence of a nephritic or nephrotic syndrome, of an alteration of glomerular
      filtration rate without any clear explanation , or of a rather advanced renal
      dysfunction (a GFR < 60 ml/min in people < 65 years or < 45 ml/min in the
      others). This paper is concerned with mild and moderate forms of kidney disease
      (stages 1 to 3). In case of progression, a closer collaboration must exist
      between the general practitioner, the nephrologist and a trained dietician to
      slow down this progression, limit its consequences and delay as long as possible
      the initiation of kidney function supplying techniques.

PMID- 16910270
TI  - [Angiotensin converting enzyme inhibitors or angiotensin II receptor blocker in
      cardiovascular and renal pathology in 2006: what does EBM teach us?].
AB  - Inhibitors of the renin-angiotensin system have proved their great value in
      secondary prevention trials for cardiovascular or renal complications. In favour
      of the preferred use of angiotensin receptor antagonists stand their excellent
      tolerance and the possible therapeutic escape seen with angiotensin converting
      enzyme inhibitors. For the preferential use of the latter, the arguments are the
      absence of a real proof of any superiority of the angiotensin receptor blockers
      and their higher cost. The wisdom is to initially use angiotensin converting
      enzyme inhibitors in secondary prevention excepted when they are not well
      tolerated. The large ONTARGET cardiovascular prevention trial should help solve
      this controversy.

PMID- 16910271
TI  - [Effects of glimepiride (Amarylle) in type 2 diabetic patients: results of the
      Belgian study RECORD in general medicine].
AB  - Sulfonylureas still have a key place in the treatment of type 2 diabetes,
      especially those of the last generation. This article describes the results of a
      post-marketing study (RECORD, Routine Evaluation Conducted On Registered Drugs
      project) focusing on glimepiride (Amarylle). This study investigated the
      efficacy, safety and tolerance of glimepiride in primary care. It was performed
      in Belgium and concerned 1.012 patients with type 2 diabetes followed for 6
      months by 204 general practitioners. Almost two thirds of recruited patients
      already received oral glucose-lowering agents whereas one third were naive
      patients. This open study showed a progressive decrease of fasting blood glucose
      and glycated haemoglobin (HbA1c) levels with glimepiride (titrated from 1 to 6
      mg/day, as needed, with a mean daily dose of 2,6 mg), together with a
      simultaneous slight reduction in body weight and without any increase of the
      hypoglycaemic risk. Primary care physicians considered both the efficacy and
      tolerance of glimepiride as good or very good in more than 90% of cases. The
      value of such a study is to provide valuable information about glimepiride use in
      real life, a condition that may differ from strict follow-up imposed in
      randomised controlled clinical trials.

PMID- 16910272
TI  - [Should the BCG vaccine still be recommended?].
AB  - The BCG vaccine has demonstrated its efficacy to protect young children from
      severe extrapulmonary forms of tuberculosis. Nevertheless, the immunity induced
      by the vaccine disappears in adults and cannot be boosted by readministration of
      BCG. Adverse effects of BCG are rare, but potentially dangerous (i.e.
      disseminated vaccinal infections) and they justify the fact that BCG should not
      be administered anymore in Western European countries where the incidence of
      pediatric tuberculous meningitis is very low. The vaccine is still recommanded
      for children living in countries with high tuberculosis prevalence and for
      resident children leaving Belgium for these countries.

PMID- 16910273
TI  - [Management of Chlamydia tracomatis pelvic infection].
AB  - The infection by Chlamydia trachomatis is a serious infection that affects the
      male and female tractus, and that induces complications such as infertility and
      extrauterine pregnancy. The antibiotic treatment needed must necessarily reach
      the intracellular milieu to be efficient enough to eradicate the infection.

PMID- 16910274
TI  - [Recurrent labial herpes. How to treat and prevent it best].
AB  - Labial herpes is a recurrent muco-cutaneous disorder caused by the herpes simplex
      virus (HSV), particularly the HSV type I. It affects 10 to 30% of the adult
      population. The recurrence rate varies from episodic events to monthly
      recurrences. Several triggering factors have been identified. They include
      physical factors such as ultraviolet radiations and any local traumatism such as
      dental and neurosurgical interventions, and dermo-cosmetic procedures of the
      face. Hormonal factors are also involved including those related to menses and
      pregnancy. Psychogenic factors, particularly severe stress are also involved. Any
      other intercurrent infection may also be complicated by recurrent labial herpes.
      The management of recurrent labial herpes currently relies on the identification
      and possible avoidance of triggering factors, and on the use of antiviral agents.
      There is no curative treatment available so far.

PMID- 16910275
TI  - [The general practitioner and insomnia].
AB  - A complaint of insomnia has to be analysed, and differentiated from hypochondria
      and, overall, from hypersomnia. Once confirmed and assessed as acute or chronic,
      it is often considered a disorder of hyperarousal, that is an imbalance between a
      central nervous system activating and a central nervous system inhibiting system
      with subcontinuous overflow from the former. An acute insomnia is less than one
      month of duration. As a disease, insomnia has to be categorized as a secondary or
      a primary disorder. Thereafter, it remains to assess the extent of social,
      psychological and economical interactions. These factors intervene as
      consequences or perpetuating factors. The capacity to assess the whole situation
      is really the great strength of the general practitioner who, more than anybody
      else, is on home ground. Laboratory findings and specialist examination come only
      as supporting evidence for causal links. A polysomnography realized in a sleep
      disorder center provides data reinforcing or correcting the diagnosis. From a
      sound assessment of the disease, the treatment has to be deduced by following a
      rigorous reasoning, devoid of guilty feelings as they are suggested to patients
      by mass-media talking, as well as freed from fashionable non medical practices.
      Today, we know that chronic insomnia is a disease with potential severe
      consequences and that it does not heal spontaneously.

PMID- 16910276
TI  - [Generic medications and prescription by non-proprietary name].
AB  - Complementarily to a previous publication, this paper tries to answer a few
      commonly asked questions about--generic medications: pharmaceutical quality,
      bioequivalence and therapeutic equivalence, substitution, etc. A summary of
      recent regulations about reference price and prescription by non-proprietary
      name, aiming at the promotion of generic medication prescription is also
      presented.

PMID- 16910277
TI  - [Role of micronutrients in medicine].
AB  - Adequate micronutrient intake throughout life course is essential for the
      maintenance of health. Micronutrients are necessary for the maintenance of
      intermediary metabolism, play a crucial role as co-factors or co-enzymes in the
      activity of virtually all enzymes, and have important functions to neutralise the
      deleterious effects of oxidant species. Claims have been made for the benefits of
      micronutrient supplementation. Clinical benefit of a supplementation is obvious
      in those individuals who are severely depleted and at risk of complications. More
      recently, the concept of subclinical deficit has been developed, which
      essentially relies upon biochemical abnormalities the interpretation of which
      remains doubtful in most instances. Symptomatology related to such subclinical
      deficit is non specific and the potential advantages of micronutrient supplements
      remain marginal and largely not well-established. In contrast, provision of
      excess supplements to individuals who do not need them may be harmful. In the
      general population, a well-balanced diet supplies an adequate intake of
      micronutrient. Further research is needed to identify the best markers of
      micronutrient and antioxidant status, so that at risk patients can be identified
      and appropriate supplementation provided accordingly. New large-scale trials of
      different doses of micronutrients, based on precise outcome markers, are required
      to optimise intakes in different groups of patients as well as in the general
      population.

PMID- 16910278
TI  - [Drug interactions: from theory to practice].
AB  - Pharmacotherapy becomes increasingly complex and therapeutic targets are more and
      more ambitious for both care and prevention. Therefore, polypharmacy is frequent,
      which exposes the patient to a high risk of drug-drug interactions. These are
      often underestimated although they are responsible for many adverse events that
      may be serious and even fatal. In the present paper, we will first briefly recall
      the main cautions in the use of medications as well as the most common conditions
      favouring the occurrence of harmful drug interactions. Then, we will analyze the
      various mechanisms leading to drug interactions, emphasizing especially those
      involving cytochrome P450 enzymatic system and P-glycoprotein. Finally, we will
      illustrate these theoretical considerations with some examples of drug
      interactions, among the most dangerous and the most frequent in clinical
      practice.

PMID- 16910279
TI  - [PPI very long-term treatment: is the problem only economic?].
AB  - Proton pump inhibitors are among the most prescribed drugs in Belgium, due to the
      high prevalence of gastrooesophageal reflux disease and significant impairment of
      health-related well-being. Short-term and long-term efficacy is superior to that
      of H2-receptor antagonists. Long-term safety is established. Empirical short-term
      treatment of symptomatic patients under 50 years of age without alarm signs is
      acceptable, but endoscopic investigation should always be performed before
      starting a long-term treatment. Doses for management of low-grade oesophagitis
      may be tailored to the patient's response. Continuous maintenance of full-dose is
      recommended for high grade oesophagitis. Surgical alternative is to be discussed
      with patients. Efficacy and mean cost for insurance plans are comparable.
      Endoscopic procedures are not yet sufficiently evaluated to be considered. Simple
      lifestyle advice is still useful. The burden of proton pump inhibitors cost is
      acceptable if they are prescribed at adequate doses. Cost-effective drugs should
      be chosen first.

PMID- 16910280
TI  - [Advices for a better drug prescription].
AB  - The prescription of a pharmacological agent concludes most medical visits. The
      rational basis of drug prescription by the physician relies on numerous
      pharmacodynamic, pharmacokinetic, pragmatic and economic considerations. However,
      it is a pity to notice that one patient out of two does not strictly follow the
      pharmacological treatment as it was prescribed. This article analyses some
      problems of the patient-doctor relationship, which may reduce medication
      compliance, and provides practical advice for improving such a situation in order
      to enhance both efficacy and safety of drug prescribing.

PMID- 16910281
TI  - [The value of mobile intensive care unit (MICU): does it remain to be proven?].
AB  - Recent international guidelines about emergency situations (ILCOR / ERC) pointed
      to the need of the whole "chain of survival". ALS, Advanced Life Support (the
      last and "medical" part of the chain ) is important and influences survival rate.
      If no doubt exists about "what" and "when" to do in such situations, there is no
      consensus in industrialized countries about "who" should be in charge of such out
      of-hospital acute diagnosis and treatment: emergency physicians, emergency
      nurses, emergency medical technicians (EMT), other "new" professionals ? ... A
      description of the MICU system in Belgium is given.

PMID- 16910282
TI  - [Medico legal issues related to driving: the role of the general practitionner].
AB  - The Belgian law requires that the physician informs his/her patient when he
      diagnoses a medical reason that makes him/her unfit to drive a vehicle. This
      paper lists, as they appear in the official texts, the physical conditions and
      diseases which may be responsible for the inaptitude to drive. Thus are detailed
      the rules applied in the presence of neurological diseases, psychic disorders,
      epilepsia, pathological sleepiness, locomotive disorders, cardiovascular disease,
      rhythm or conduction disturbances, blood pressure abnormalities, coronary or
      myocardial disease, and hearing loss or vestibular problems. The reader will also
      find a summary of the rules related to visual ability, alcohol use, driving under
      the influence of psychotropic drugs, or medicines in general, renal or hepatic
      diseases, and to the patient who received an organ transplant or an artificial
      implant. The responsibility of the physician, primarily the general practionner,
      may be involved in these matters; this issue is discussed.

PMID- 16910283
TI  - [Management of intrafamily violence issues by general practitioners].
AB  - General practitioners often come upon intrafamily abuse cases in their practice.
      They are either specifically consulted because of these instances of abuse or
      they discover them by accident. When this happens, they are often unsure of the
      appropriate procedure to follow, for fear of committing a medical fault or
      breaking the law. The aim of this short article is not to dwell on the diagnostic
      methodologies, but to provide a series of general guidelines to follow in
      everyday practice.

PMID- 16910284
TI  - [The medical decision for the non-competent patient].
AB  - The evolution of the therapeutic relation from a paternalistic to a collaborative
      one has increased the legal and ethical problems related to the medical care in
      non competent patients. The recent Belgian law on the rights of the patient
      (August 22, 2002 ) and the advice of the Belgian Council of the Medical
      Association on this matter provide the practitioner with clear directives.
      However, the responsibility of the final decision always remains in the hands of
      the medical doctor as the protector of the patient.

PMID- 16910285
TI  - [Some Websites frequently used in general practice].
AB  - Internet use is booming worldwide. The general practitioner can find on the Web a
      significant help for his research of information, as well as for his medical
      practice and the administrative management of his office. The proportion of
      general practitioners who make use of Internet in their professional life is
      constantly increasing, but their major difficulty remains to know where to
      quickly find the reliable information. The purpose of this paper is to describe
      ten Websites of particular interest in general practice.

PMID- 16910286
TI  - Comparative assessment of aluminum and lead concentrations in serum and tissue
      bioptates in patients with laryngeal papilloma or cancer.
AB  - A comparative assessment of toxic element concentrations in serum and tissue
      bioptates in patients with laryngeal papilloma or cancer was performed.
      Examinations were conducted in 60 patients (40 men and 20 women) aged 20-88 years
      (average 59 +/- 05). Patients were divided into 3 groups; 20 patients with
      laryngeal papilloma were in group I, 20 with laryngeal cancer were in group II,
      and 20 with deviated nasal septums were included as a control group (III).
      Diagnosis of laryngeal papilloma (removed by direct microlaryngoscopy-
      Kleinsasser method) and laryngeal cancer (removed by the Rethi method) was
      histopatologically confirmed in patients from groups I and II, respectively.
      Patients in the control group received functional surgery to repair deviated
      nasal septums. Serum and tissue samples were obtained from all patients before
      surgery. Aluminum and lead concentrations were analysed by inductively coupled
      plasma atomic emission spectrometry (ICP-AES) using a Spectroflame M
      spectrometer. The considerable rise of aluminum and lead concentration in tissue
      bioptates and aluminum in serum in groups I and II in comparison to the control
      group suggests that these elements may play a significant part in the aetiology
      and development of precancerous lesions and laryngeal cancers. Measuring toxic
      chemical element concentrations in tissue bioptates can be useful in the
      diagnosis and estimation of development of precancerous lesions of the larynx as
      well as laryngeal cancer. Toxic elements concentration may play a significant
      role in carcinogenesis and may determine trends in cancer aetiology.

PMID- 16910287
TI  - Papillomatosis of the larynx: treatment with CO2 laser.
AB  - OBJECTIVES: We report our experience treating papillomatosis of the larynx using
      CO2 laser which has a lower risk of post surgical complications. Papillomatosis
      has a high incidence of recurrence after surgical treatment. METHODS: We treated
      42 patients (10 adults and 32 children) affected by multiple papillomatosis of
      the larynx. Smaller papillomas were vaporized with a 7-8 Watt CO2 laser and
      larger papillomas were resected at the base of their implantation. A strict
      follow-up during the first 3 years after surgical treatment was necessary to
      manage recurrences with CO2 laser endoscopy. RESULTS: All patients presented with
      recurrences after the first surgical treatment, but within 18-60 months all
      patients presented a solution of their pathology. Post-operative complications
      were observed in patients who did not comply with the strict follow-up protocol
      and presented with large lesions requiring more invasive surgery. CONCLUSIONS:
      CO2 laser endoscopy, although it did not prevent recurrences of papillomatosis in
      the larynx, is a valid surgical approach in the management of this pathology.

PMID- 16910288
TI  - Levocetirizine as treatment for symptoms of seasonal allergic rhinitis.
AB  - OBJECTIVES: The aim of this study was to assess the effectiveness and safety of
      levocetirizine in the treatment of the symptoms of seasonal allergic rhinitis
      (SAR) in patients consulting their primary care doctor. METHODS: Open-label
      uncontrolled and non-randomised multi-centre study including patients presenting
      symptoms of SAR and treated with levocetirizine tablets, 5 mg OD, for 4 weeks.
      INCLUSION CRITERIA: patients with nasal symptoms who were not on treatment or not
      responsive to treatment, or affected by excessive adverse events due to the
      antihistamines used previously. There were two visits (initial and after four
      weeks). Primary end point: efficacy as measured by T4SS (combined score of
      sneezing, rhinorrhoea, nasal and ocular pruritus, ranging from 0 to 12 recorded
      by the patient); change in Clinical Global Impression (CGI-c) as rated by the
      general practitioner, subjective satisfaction with and preference for
      levocetirizine. Secondary end points: treatment-related adverse events. RESULTS:
      1290 patients were evaluated. Before the start of the study, 61.2% did not use
      any medication, 36.4% took anti-histamines which were not effective, and 27.0% of
      those previously treated patients experienced excessive adverse events.
      Statistically significant decreases (p < 0.01) compared to baseline were observed
      for each individual symptom of the itemised T4SS as well as for the global T4SS.
      The CGI-c improved in 91.1% of the patients who had received treatment previously
      and 96.8% of those who had not. Of the patients who had received treatment
      previously, 91.7% (p < 0.01) were satisfied with the study treatment and 84.5% of
      these patients reported they would prefer levocetirizine in future. All adverse
      events (somnolence, fatigue, headache, dry mouth) decreased by comparison with
      previous treatments after levocetirizine was used. CONCLUSION: Levocetirizine
      showed an improvement in symptom control for SAR and was preferred by patients
      compared to the antihistamines they had taken previously. Levocetirizine was well
      tolerated.

PMID- 16910289
TI  - Speech discrimination and intelligibility: outcome of deaf children fitted with
      hearing aids or cochlear implants.
AB  - We retrospectively studied outcome of a sample of 36 congenitally deaf children
      who were fitted with either a conventional hearing aid (HA, N = 14) or a cochlear
      implant (CI, N = 22), and who received many years of audio-phonatory training by
      our multi-disciplinary team. In order to rate speech discrimination perception,
      we developed a new metric of speech discrimination performance based on several
      existing discrimination tests for the French language. Speech perception skills
      were measured with and without lip-reading cues. We also studied the evolution of
      auditory capacity in real-life situations, and the evolution of the
      intelligibility of spoken language during a five year period. To rate auditory
      capacity and speech intelligibility, we used commonly used metrics: CAP and SIR.
      During the five successive years of observation, CAP and SIR scores improve for
      both the HA and CI children. Improvement, however, is more pronounced for the CI
      children. At the end of the 5-years period, CAP and SIR scores of CI children are
      significantly higher than those of HA children. Our study is one of few that
      evaluates outcome of HA and CI fitting with age matched congenitally deaf
      children anno 2000.

PMID- 16910290
TI  - Hyperbaric oxygen therapy after failure of conventional therapy for sudden
      deafness.
AB  - PROBLEMS/OBJECTIVES: We investigated the effect of secondary hyperbaric oxygen
      therapy (HBO) for patients with idiopathic sudden sensorineural hearing loss
      after unsuccessful conventional treatment. METHODOLOGY: We retrospectively
      evaluated 3 groups: 100 patients without further treatment (group 1), 160
      patients with secondary HBO at 1.5 ATA (group 2), and 56 patients with secondary
      HBO at 2.5 ATA (group 3). RESULTS: In group 1, a mean hearing gain (MHG) of 2.6
      +/- 15 dB was found at the end of the follow-up period. After HBO, a MHG of 3.1
      +/- 9 dB in group 2 and 19.7 +/- 23 dB in group 3 was achieved. The results in
      group 3 were statistically significant in comparison to group 1 (p < 0.007) and
      to group 2 (p < 0.009). With HBO after initial therapy failure, there is a
      significant correlation of MHG with time delay before HBO (p < 0.03).
      CONCLUSIONS: HBO at 2.5 ATA in patients with idiopathic sudden sensorineural
      hearing loss after unsuccessful conventional treatment yields significant
      improvement of hearing. MHG is higher when time delay before HBO is shorter.

PMID- 16910291
TI  - Test-retest reliability of the Dutch version of the Dizziness Handicap Inventory.
AB  - In the last fifteen years the Dizziness Handicap Inventory (DHI) has gained wide
      acceptance as a useful measure of handicap resulting from dizziness and
      unsteadiness. The objective of this study was to calculate measurement error and
      test-retest reliability of the Dutch version of the DHI. The translation into
      Dutch was performed according to a double translation method. One hundred and six
      patients with balance problems (range 26-78 years), scheduled for vestibular
      rehabilitation, completed the DHI on two occasions on the same day. The test
      retest reliability was excellent, with Intraclass Correlation Coefficients
      ranging from 0.94 to 0.99 for DHI sub-scores and DHI total score. Most weighted
      kappa values (kappaW) exceeded 0.80 indicating substantial item per item test
      retest reliability. Over 80% agreement was noted for all items except for item 8
      (74%). Item 8 asks whether the subject feels dizzy or unsteady while doing
      ambitious activities like sports, dancing and household activities. Consequently
      measurement errors were calculated, suggesting that, after an intervention, the
      pretreatment DHI total score should at least decrease with 12 points (lower bound
      99% confidence interval for a true change) before the intervention could be said
      to be effective for an individual patient. Based on these data, the Dutch version
      of the DHI showed itself to be a highly reliable instrument to assess the self
      perceived handicap imposed by vestibular system diseases.

PMID- 16910292
TI  - The Panoti and some other fantastic forms of macrotia.
AB  - "He had the form of a human being... His ears were as long as clusters of dates
      or elephant ears, and they covered his shoulders" ("The thousand and one nights",
      Sinbad the sailor, 546th night, circa IXth century AD). "About his ears, I shall
      tell you all the truth: They have the capacity of about 300 liters. When he is
      surprised by wind or tempest, He can immediately cover his head. He does not
      frighten the water at all, Even if it rained enormously during one full month.
      The other ear, he uses as a shield. It is hanging in front of his face up to his
      baldric. Thanks to his ears, he does not fear any feathered arrow, steel lame, or
      chiselled spear" (The ears of Isabras in "La Bataille Loquifer", or "Geste de
      Rainouard", from the "Geste de Guillaume d'Orange", XIIIth cent. "In that
      neighbouring isle, I heard someone saying that there were men whose ears were so
      big that they were able to cover their arms with them. That people are the
      Caphri".

PMID- 16910293
TI  - Laryngeal tuberculosis presenting as supraglottic carcinoma: case report and
      literature review.
AB  - Laryngeal tuberculosis is a rare extra-pulmonary manifestation of tuberculosis,
      and frequently presents with tumour-like symptoms and clinical findings. Uncommon
      clinical features are to be expected by the ENT specialist, who should be aware
      of these recently changing presentations. Despite the dramatic reduction of the
      incidence of the disease during the last few decades, a perceptible increase in
      case reports has lately been noted and may prove significant. Treatment remains
      conservative and long-term follow-up is suggested. A relevant case of laryngeal
      tuberculosis presenting as a supraglottic carcinoma is presented, its diagnosis
      and management are detailed, and suggestions are offered based on a literature
      review.

PMID- 16910294
TI  - A correlation between age and Actinomyces in the adenotonsillar tissue of
      children.
AB  - The purpose of this study was to investigate the presence of actinomyces in
      adenotonsillar disease, recurrent infections, or tonsillar hypertrophy in
      children. The study included 64 patients, ranging in age from 2 to 16 years, who
      had elective adenotonsillar surgery to treat either adenotonsillar hypertrophy
      (36 children) or recurrent adenotonsillitis (28 children). Adenotonsillar
      Actinomyces was present in 30 children (48%). No statistical significance was
      found between Actinomyces and recurrent adenotonsillitis or adenotonsillar
      hypertrophy. However, there was a statistically significant relationship
      identified between the presence of actinomycosis and age, with a greater
      occurrence of actinomycosis in children between 5 and 16 years old.

PMID- 16910295
TI  - A historical vignette. Turbulence around the otoliths. Sappey's hostility and
      Breschet's defence.
AB  - Nowadays, the animosity between medical scholars is seldom apparent. However,
      during the XIXth century it was not necessarily so. We find an example of this in
      Sappey's hostility against his colleague anatomist Gilbert Breschet. It concerned
      the discovery of the otoliths of the inner ear that Breschet attributed to
      himself. We present here Breschet's defence.

PMID- 16910296
TI  - [Investigations concerning the threshold value between endogenous and exogenous
      GHB (liquid ecstasy)].
AB  - The article describes critical investigations concerning the threshold value
      between endogenous and exogenous concentrations of gamma-hydroxybutyric acid
      (GHB/"liquid ecstasy") in human blood. The values of GHB in the blood samples of
      50 blood donors and 50 postmortem cases were measured with a validated gas
      chromatographic/mass-spectrometric procedure according to the guidelines of the
      GTFCh (Society of Toxicological and Forensic Chemistry). GHB-concentrations were
      found to range between 0.11 and 1.56 mg/L (mean value 0.54 mg/L/standard
      deviation 0.37 mg/L/coefficient of variation 68.4 %) in the donors' blood, and
      between 2.2 and 116 mg/L (mean value 32.4 mg/L/standard deviation 25.6
      mg/L/coefficient of variation 79 %) in the postmortem samples, respectively.

PMID- 16910297
TI  - [Effect of "Fit" dishwashing detergent from former Eastern Germany (GDR) on
      luminol luminescence].
AB  - The forensic luminol test is used to screen large areas for the presence of
      blood. The heme-induced reduction of hydrogen peroxide is coupled to the
      oxidation of luminol resulting in luminescence. However, photographic
      documentation of the relatively weak and short-lived luminescence is difficult
      and luminol is now often replaced by other chemicals. In this study, we
      investigated reports from the Rostock police department that the addition of
      "Fit", a dishwashing detergent from former Eastern Germany, could both intensify
      and prolong the luminescence of luminol on blood stains. Even though this effect
      was reported only for the original composition of Fit but not the currently sold
      version, we found that both the old and the new version of Fit increase the
      brightness of the luminescence while decreasing its duration. This may be due to
      detergents in the dishwashing liquid, which permeabilize the plasma membrane of
      the erythrocytes, exposing the Fe3+ inside the cell and speeding up the entire
      reaction. We did not find any evidence of special ingredients in the old version
      of Fit that would cause both the increased brightness and prolonged duration of
      luminescence as reported by the Rostock PD.

PMID- 16910298
TI  - [Interdisciplinary cooperation of forensic sciences--results of a simulation
      exercise].
AB  - In a workshop held on the occasion of the foundation of the INFW, the
      Interdisciplinary Network of Forensic Sciences (www.infw.org), 14 scientists from
      10 fields of expertise were allotted to 3 teams. Each team had to independently
      solve the same fictitious forensic case. In this, several corpses or skeletons in
      varying degrees of decomposition were found in the remains of an old bunker
      during a large building project. After a set time limit of 45 minutes, the
      approaches to the task were noted on individual flipcharts by each team. A
      comparison of the solutions suggested by the three very heterogeneously composed
      teams revealed a high degree of similarity. However, particularly the "exotic"
      disciplines developed surprising approaches. The experiment was an interesting
      and instructive experience for all participants and underscores the necessity of
      interdisciplinary cooperation in solving complex forensic questions.

PMID- 16910299
TI  - [Lethal mixed intoxication with propofol in a medical layman].
AB  - The authors report on a drug fatality of a 21-year-old man with a propofol (2,6
      di-isopropylphenol) dependency. Propofol was detected in tissues and body fluids
      using SPME-GC/MS methods. The postmortem concentrations of propofol were 364
      ng/ml in urine, 71 ng/ml in heart blood and 79 ng/ml in femoral blood. The drug
      addict had only an autodidactic medical knowledge, but had inserted himself a
      permanent cannula for intravenous injection of propofol several times a day. The
      injection material was bought via online auctions from eBay. The case illustrates
      how job-related drug dependencies become indistinct due to the free access to
      information and goods via the Internet.

PMID- 16910300
TI  - [Fulminant liver failure in a patient on carbamazepine and levetiracetam
      treatment associated with status epilepticus].
AB  - A 22-year-old female with a history of developmental delay and seizures
      successfully treated with carbamazepine and levetiracetam developed fulminant
      hepatic failure and subsequently died. She had been admitted to the hospital
      following secondary generalized seizures of 35 min duration. A circulatory shock
      as well as intoxication was taken into consideration during the clinical course.
      Autopsy failed to reveal a macroscopically discernible cause of death.
      Significant findings on microscopic examination included acute tubular necrosis
      in the kidneys, pre-existing marked accumulation of neutral lipid within the
      hepatocytes as well as hyperacute liver damage with evidence of almost complete
      hepatocyte necrosis. Carbamazepine and levetiracetam were simultaneously
      determined from blood and tissues such as liver, lungs, muscle and kidneys by LC
      MS/MS following addition of lamotrigine as an internal standard and liquid-liquid
      extraction. Validation data are given for levetiracetam. Both carbamazepine and
      levetiracetam were present in blood at concentrations within or below the
      therapeutic range, respectively. Moreover, tissue concentrations suggested long
      term administration of anticonvulsant drugs, which is in accordance with the
      medical history. After excessive drug concentrations could be ruled out, the
      metabolic consequences of a prolonged carbamazepine therapy to cause severe
      hepatic injury in the present case are discussed. A mechanism of injury to the
      hepatocytes may be membrane damage by either an increased production of free
      radicals and/or a decreased free radical scavenging capacity. Following ischemia
      with reperfusion and during hyperthermia, large amounts of free radicals are
      formed. Induction of the mixed oxidase activity during longterm administration of
      carbamazepine may also increase production of free radicals, leaving the hepatic
      cell more vulnerable to oxidative injury.

PMID- 16910301
TI  - [Opportunities and challenges for both national and international public health
      area--the public health sector in government--].
AB  - To inform choices about the future of people who study public health and
      preventive medicine, the current status of public health is examined in terms of
      the public health sector in government. After tracing the major achievements of
      public health in the modern era, this paper explores the potential of public
      health and its core functions, which is realized by public health professionals
      working in the government sector. Finally, this article highlights the
      international dimension of public health, which is becoming increasingly
      important and therefore attracting many people who would like to take part.

PMID- 16910302
TI  - [Curriculum of health promotion and disease prevention for the 21st century--the
      5th revision of preventive medicine learning objectives--].
AB  - The preventive medicine learning objectives, first developed in 1977 and
      subsequently supplemented, underwent necessary revision of the contents for the
      fourth time to create the fifth revision. However, the required educational
      contents of health promotion and disease prevention have been changed by the new
      trends of medical education such as PBL and integrated curriculum, the rapid
      change of the health and medical environment and the globalization of medicine.
      The Korean Society of Preventive Medicine formed a task force, led by the
      Undergraduate Education Committee in 2003, which surveyed all the medical
      colleges to describe the state of preventive medicine education in Korea,
      analyzed the changing education demand according to the change of health
      environment and quantitatively measured the validity and usefulness of each
      learning objective in the previous curriculum. Based on these data, some
      temporary objectives were formed and promulgated to all the medical schools.
      After multiple revisions, an almost completely new series of learning objectives
      for preventive medicine was created. The objectives comprised 4 classifications
      and 1 supplement: 1) health and disease, 2) epidemiology and its application, 3)
      environment and health, 4) patient-doctor-society, and supplementary clinical
      occupational health. The total number of learning objectives, contained within 13
      sub-classifications, was 221 (including 35 of supplementary clinical occupational
      health). Future studies of the learning process and ongoing development of
      teaching materials according to the new learning objectives should be undertaken
      with persistence in order to ensure the progress of preventive medicine
      education.

PMID- 16910303
TI  - [Does living nearby a garbage dumping site degrade the quality of life? A case
      study based on Shin-dong Myeon residents, Chun-cheon Si].
AB  - OBJECTIVES: This study aims to examine if a garbage dumping site has real and
      negative influence on the quality of life (QOL) for the nearby residents. The net
      effects of the residential distance from the garbage dumping site and from the
      garbage truck route were investigated for five domains of the QOL. METHODS: Two
      hundred fifty seven Shin-dong Myeon residents, Chun-cheon Si, participated in a
      self-administrated survey. The Shin-dong Myeon garbage dumping site began
      operating in 1996. ANCOVA with generalized linear models and multiple regression
      analysis were performed. RESULTS: Descriptive analyses show that a residence
      nearby a garbage dumping site is negatively associated with the physical and
      environmental domains of the QOL. The residential distance from the garbage truck
      route does not exert any significant effect on various domains of QOL, except for
      the environmental domain. On the multivariate analysis, the residents living near
      the garbage dumping site tended to have a significantly negative QOL in the
      physical and environmental domains. However, the distance from the garbage truck
      route did not show a significant nor substantial effect on the QOL. The
      demographic and socioeconomic control variables are associated with a number of
      the QOL domains, and their patterns are consistent with the general expectations.
      CONCLUSIONS: The results indicated that a garbage dumping site is considered to
      be an environmental hazard among the nearby residents according to the lower
      scores on the physical and environmental domains of the QOL. The findings from
      this study provide comprehensive? understanding on the residents' QOL, and they
      may help politicians and policy makers make decisions for appropriate
      interventions.

PMID- 16910304
TI  - [Effects of air pollution on asthma in Seoul: comparisons across subject
      characteristics].
AB  - OBJECTIVES: Korean epidemiological studies have used reduced samples according to
      the subject's characteristics, such as the health services provided, the
      historical note with asthma, and age, to examine the acute effect of air
      pollution on asthma using the Korean National Health Insurance records. However,
      there have been few studies on whether the effects shown in these reduced samples
      are different from those of all samples. This study compared the effects of air
      pollution on asthma attacks in three reduced samples with those of entire
      samples. METHODS: The air pollution data for PM10, CO, SO2, NO2, and O3 and
      weather conditions including temperature, relative humidity, and air pressure in
      Seoul, 2002, were obtained from outdoor monitoring stations in Seoul. The
      emergency hospital visits with an asthma attack in Seoul, 2002 were extracted
      from the Korean National Health Insurance records. From these, the reduced
      samples were created by health service, historical notes with asthma, and age. A
      case-crossover design was adopted and the acute effects of air pollution on
      asthma were estimated after adjusting for weather, time trend, and seasonality.
      The model was applied to each reduced sample and the entire sample. RESULTS: With
      respect to the health service, the effects on outpatients were similar to those
      for the total sample but were different for inpatients. These similar effect
      sizes were also observed in the reduced samples according to the historical note
      with asthma and age. The relative risks of PM10, CO, SO2, NO2, and O3 among the
      reduced and entire samples were 1.03, 1.04-1.05, 1.02-1.03, 1.04-1.06, and 1.10
      1.17, respectively. CONCLUSIONS: There was no clear evidence to show a difference
      between the reduced samples and the entire samples.

PMID- 16910305
TI  - [Estimation of smoking prevalence among adolescents in a community by design
      based analysis].
AB  - OBJECTIVES: This study was conducted to estimate the unbiased smoking prevalence
      and its standard errors among adolescents in a large city in Korea, by design
      based analysis. METHODS: All the students in Daegu city were stratified by grade,
      gender and region, and then schools as primary sampling units (PSU) were selected
      by probability proportional to size (PPS) sampling. One or two classes were
      sampled randomly from each grade, from 5th grade in elementary schools to the 3rd
      grade in high schools. The students anonymously completed a standardized self
      administered questionnaire from October to December 2004. The total number of
      respondents was 8,480 in the final analysis, excluding the third graders in the
      general high schools because of incomplete sampling. The sampling weight was
      calculated for each student after post-stratification adjustment, with adjustment
      being made for the missing cases. The data were analyzed with Stata 8.0 with
      consideration of PSU, weighting and the strata variables. RESULTS: The smoking
      prevalence (%) and standard errors for male students from the fifth grade in
      elementary schools to the second grade in high schools were 0.93 +/- 0.47, 1.83
      +/- 0.74, 3.16 +/- 1.00, 5.12 +/- 1.02, 10.86 +/- 1.13, 15.63 +/-2.44 and 17.96
      +/- 2.67, and those for the female students were 0.28 +/- 0.28, 1.17 +/- 0.73,
      3.13 +/- 0.60, 1.45 +/- 0.58, 3.94 +/- 0.92, 8.75 +/- 1.86 and 10.04 +/- 1.70,
      sequentially. CONCLUSIONS: The smoking prevalence from this study was much higher
      than those from the other conventional studies conducted in Korea. The point
      estimates and standard errors from the design-based analysis were different from
      those of the model-based analysis. These findings suggest the importance of
      design-based analysis to estimate unbiased prevalence and standard errors in
      complex survey data and this method is recommended to apply to future surveys for
      determining the smoking, prevalence for specific population.

PMID- 16910306
TI  - [Distribution of airborne fungi, particulate matter and carbon dioxide in Seoul
      metropolitan subway stations].
AB  - OBJECTIVES: The aims of this study were to examine the level of airborne fungi
      and environmental factors in Seoul metropolitan subway stations and to provide
      fundamental data to protect the health of subway workers and passengers. METHODS:
      The field survey was performed from November in 2004 to February in 2005. A total
      22 subway stations located at Seoul subway lines 1-4 were randomly selected. The
      measurement points were subway workers' activity areas (station office, bedroom,
      ticket office and driver's seat) and the passengers' activity areas (station
      precincts, inside train and platform). Air sampling for collecting airborne fungi
      was carried out using a one-stage cascade impactor. The PM and CO2 were measured
      using an electronic direct recorder and detecting tube, respectively. RESULTS: In
      the activity areas of the subway workers and passengers, the mean concentrations
      of airborne fungi were relatively higher in the workers' bedroom and station
      precinct whereas the concentration of particulate matter, PM10 and PM2.5, were
      relatively higher in the platform, inside the train and driver's seat than in the
      other activity areas. There was no significant difference in the concentration of
      airborne fungi between the underground and ground activity areas of the subway.
      The mean PM10 and PM2.5 concentration in the platform located at underground was
      significantly higher than that of the ground (p<0.05). CONCLUSIONS: The levels of
      airborne fungi in the Seoul subway line 1-4 were not serious enough to cause
      respiratory disease in subway workers and passengers. This indicates that there
      is little correlation between airborne fungi and particulate matter.

PMID- 16910307
TI  - [Women's willingness to pay for cancer screening].
AB  - OBJECTIVES: The goal of this study is to measure women's willingness to pay for
      cancer screening and to identify those factors associated with this willingness
      to pay METHODS: A population-based telephone survey was performed on 1,562 women
      (aged 30 years or over) for 2 weeks (9-23th, July, 2004). Data about
      sociodemographic characteristics, health behaviors, the intention of the cancer
      screenings and willingness to pay for cancer screening were collected. 1,400
      respondents were included in the analysis. The women's willingness to pay for
      cancer screening and the factors associated with this willingness to pay were
      evaluated. RESULTS: The results show that 76% of all respondents have a
      willingness to pay for cancer screening. Among those who are willing to pay, the
      average and median amount of money for which the respondents are willing to pay
      are 126,636 (s.d.: 58,414) and 120,000 won, respectively. As the status of
      education & the income are higher, the average amount that women are willing to
      pay becomes much more. The amount of money women are willing to pay is the
      highest during the 'contemplation' stage. Being willing to pay or not is
      associated with a change of behavior (transtheoretical model), the income, the
      concern about the cancer risk, the family cancer history, the marital status, the
      general health exam, age and the place of residence. Income is associated with a
      greater willingness to pay. Old age was associated with a lower willingness to
      pay. CONCLUSIONS: According to the two-part model, income and TTM are the most
      important variables associated with the willingness to pay for cancer screening.
      The cancer screening participation rate is low compared with the willingness to
      pay for cancer screening. It is thought that we have to consider the
      participants' behavior that's associated with cancer screening and their
      willingness to pay in order to organize and manage cancer screening program.

PMID- 16910308
TI  - [Changes in smoking status among current male smokers and factors associated with
      smoking cessation success].
AB  - OBJECTIVES: This study (a) investigated the rate of smoking cessation sucess for
      current male smokers, and (b) identified the factors that are associated with the
      smoking cessation success. METHODS: Data were collected from four follow-up
      surveys of 700 current male smokers. The follow-up period was from December 2004
      to June 2005. Success of smoking cessation was defined as "maintaining a smoking
      cessation status for six months". The demographic and socioeconomic factors
      included age, the household income level and, occupation. The smoking behavioral
      factors were composed of the amount of smoking, the duration of smoking, the age
      of initiating smoking, the willingness to quit, the frequency of trying to quit
      smoking and the smoker's attitude toward the anti-smoking policies. RESULTS: The
      proportion of quitters increased from 6.6% to 11.0% during the follow-up period.
      The majority of quitters answered that the increase of tobacco price acted as cue
      to achieve smoking cessation. The age-standardized experience and success rate of
      smoking cessation were 16.0% (95% C.I.=13.0% to, 19.0%) and 4.5% (95% C.I.=3.0%
      to, 6.0%), respectively. On the multivariate analysis, success for smoking
      cessation was associated with the willingness to quit smoking, low prior tobacco
      consumption, and agreement on the tobacco price increase. CONCLUSIONS: The
      results of this study suggest that the recent anti-smoking policies provided an
      opportunity to quit smoking. The results of this study can be used to establish
      evidence for further anti-smoking policies.

PMID- 16910309
TI  - [A study on scheduling periodic examinations for the early detection of breast
      cancer in Korea].
AB  - OBJECTIVES: The purposes of this study were to propose a screening schedule for
      the early detection of breast cancer among Korean women, as based on the
      statistical model, and to compare the efficacy of the proposed screening schedule
      with the current recommendations. METHODS: The development of the screening
      schedule for breast cancer closely followed the work of Lee and Zelen (1998). We
      calculated the age-specific breast cancer incidence rate from the Korea Central
      Cancer Registry (2003), and then we estimated the scheduling of periodic
      examinations for the early detection of breast cancer, using mammography, and
      based on the threshold method. The efficacy of the derived screening schedule was
      evaluated by the schedule sensitivity. RESULTS: For estimating the screening
      schedule threshold method, we set the threshold value as the probability of being
      in the preclinical stage at age 35, the sensitivity of mammography as 0.9 and the
      mean sojourn time in the preclinical stage as 4 years. This method generated 14
      examinations within the age interval [40, 69] of 40.0, 41.3, 42.7, 44.1, 45.4,
      46.7, 48.0, 49.3, 51.0, 53.2, 55.3, 57.1, 59.0 and 63.6 years, and the schedule
      sensitivity was 75.4%. The proposed screening schedule detected 85.2% (74.5/87.4)
      of the cases that could have been detected by annual screening, but it required
      only about 48.7% (14.0/30.0) of the total number of examinations. We also
      examined the threshold screening schedules for a range of sensitivities of
      mammography and the mean sojourn time in the preclinical stage. CONCLUSIONS: The
      proposed screening schedule for breast cancer with using the threshold method
      will be helpful to provide guidelines for a public health program for choosing an
      effective screening schedule for breast cancer among Korean women.

PMID- 16910310
TI  - [Serum gamma-glutamyltransferase levels and the risks of impaired fasting glucose
      in healthy men: a 2-year follow-up].
AB  - OBJECTIVES: An increase in the serum gamma-glutamyltransferase (GGT)
      concentration has been regarded as a marker of alcohol drinking or liver disease.
      Some reports, however, have suggested that the serum GGT may be a sensitive and
      early biomarker for the development of prediabetes and diabetes. In this study we
      investigated whether serum GGT is a reliable predictor of the incident impaired
      fasting glucose (IFG), including diabetes. METHODS: We performed a prospective
      study for two years (2002-2004). We analyzed the periodic health examination data
      from a total of 4,711 men. The examinations were done in the years 2002 and 2004.
      The analyzed data included a self-questionnaire, a physical examination and the
      laboratory results. Both IFG and diabetes were defined as a serum fasting glucose
      concentration of more than 100 mg/dL and 126 mg/dL, respectively. RESULTS: A
      total of 738 cases (15.7%) of incident IFG and 13 cases (0.3%) of diabetes
      occurred. The mean serum GGT concentrations were quite different between the
      normal (38.0 IU) and incident IFG groups (50.3 IU), and the incident diabetes
      group (66.0 IU) (p <0.001). After multivariable adjustment, the relative risks
      for incident IFG or diabetes across the baseline GGT categories (<10th, 10th
      20th, 30th-40th, 50th-60th, 70th-80th and >90th percentile) were 1.0, 1.172
      (0.769-1.785), 1.107 (0.725-1.689), 1.444 (0.934-2.232), 2.061 (1.401-3.031) and
      2.545 (1.784-3.631) (p-value for trend: <0.001). The risks significantly
      increased with increasing levels of GGT for 2 years; when comparing the increased
      groups (<10%, .10-20%, >20%) versus the decreased over 20% group of GGT, the
      risks for IFG or diabetes were 1.334 (1.002-1.776), 1.613 (1.183-2.199) and 1.399
      (1.092-1.794). CONCLUSIONS: Our findings suggest that serum GGT concentrations
      within its normal range may be an early predictor of the development of IFG and
      diabetes. As serum GGT is a relatively inexpensive test and a reliable marker, it
      might have important implications in public health promotion.

PMID- 16910311
TI  - [The relationship between socioeconomic position and the predicted risk of
      ischemic heart disease with using health risk appraisal].
AB  - OBJECTIVES: The object of this study is to assess the relationship between
      socioeconomic factors and the predicted 10-year risk of cardiovascular disease by
      using health risk appraisal of ischemic heart disease. METHODS: The study
      population was taken from The 2001 Korea National Health and Nutrition Survey,
      and it consisted of 1,566 men and 1,984 women aged 30-59. We calculated 10-year
      risk using the risk function of ischemic heart disease as developed by Jee. The
      educational level and equivalized household income were dichotomized by a 12
      years education period and the median income level. Occupation was dichotomized
      into manual/non-manual work. We stratified the population by age (10 years) and
      sex, and then we rated the risk differences according to socioeconomic factors by
      performing t-tests for each strata. RESULTS: There were gradients of the
      predicted 10-year risk of ischemic heart disease with the educational level and
      the equivalized household income, and thet was an increasing tendency of risk
      differences with age. Manual workers didn't show significant risk difference from
      non-manual workers. CONCLUSIONS: There was definite relationship between low
      socioeconomic position and the predicted risk of ischemic heart disease in the
      future.

PMID- 16910312
TI  - [Occupational differentials in cigarette smoking in South Korea: findings from
      the 2003 Social Statistics Survey].
AB  - OBJECTIVES: The purpose of this study was to investigate the differences in
      smoking rates according to the major occupational categories in South Korea.
      METHODS: The study subjects were a weighted sample of 24,495 men and 26,121 women
      aged 25-64 from the 2003 Social Statistics Survey, which was conducted by the
      Korea National Statistical Office. Occupation was classified according to the
      Korean Standard Occupation Classification. We computed the age-standardized
      smoking rates according to gender and occupations after adjusting for the
      education level, marital status, and self-rated health. RESULTS: For men, the
      smoking rate in elementary occupations was two times higher than that of clerks
      (OR= 1.98, 95% CI=1.74-2.26). In general, a more prestigious job(professionals)
      correlated with lower smoking rates, and less prestigious jobs correlated with
      higher smoking rates, except for legislators, senior officials and managers. For
      women, smoking among service workers was 4.1 times higher than among clerical
      workers (OR=4.11, 95% CI= 2.87-5.88). For women, their occupations, except
      elementary workers, and the unemployed, the retired and the armed forces, failed
      to show significant differences in smoking compared with the clerical workers.
      After adjusting for education, occupational differences in the smoking rate for
      men were attenuated in most occupations, except for legislators, professionals,
      and technicians. Further adjustment for marital status and self-rated health had
      a minimal effect on the occupational differences in the smoking rate for men. For
      women workers with service or elementary occupations, the ORs of smoking were
      attenuated with adjustment of the educational levels. However, the ORs of smoking
      were increased in workers with service, sales or elementary occupations, as well
      as for legislators, and the unemployed, the retired and the armed forces, after
      additionally adjusting for marital status. CONCLUSIONS: More prestigious jobs
      generally correlated with lower smoking rates in both sexes. The anti-tobacco
      policy should consider smoking rate differentials by occupations.

PMID- 16910313
TI  - Piperine, an active principle from Piper nigrum, modulates hormonal and apo
      lipoprotein profiles in hyperlipidemic rats.
AB  - PURPOSE: To study the effect of piperine, an alkaloid, on thyroid hormones and
      apolipoproteins in high-fat-diet (HFD) and antithyroid drug-induced
      hyperlipidemic rats. EXPERIMENTAL: Male Wistar rats were first divided into two
      groups, control diet and high-fat diet (HFD) and then subdivided into four
      subgroups of ten animals each. The animals were treated with the following
      regimens for 10 weeks: 1% carboxymethyl cellulose; 10 mg carbimazole (CM)/kg body
      weight; 10 mg CM + 40 mg piperine/kg body weight, and 10 mg CM + 2 mg
      atorvastatin /ATV//kg body weight. Lipid profiles, hormone levels, and
      apolipoprotein levels were studied in all groups. RESULTS: HFD and/or CM
      administration significantly elevated the plasma levels of total cholesterol,
      VLDL, LDL, triglycerides, free fatty acids, and phospholipids, but significantly
      reduced the HDL levels. Moreover, CM administration significantly reduced apo A-I
      levels and T3, T4 and testosterone levels while significantly elevating plasma
      apo B, thyroid stimulating hormone (TSH) and insulin levels. The simultaneous
      administration of piperine and HFD significantly reduced plasma lipids and
      lipoproteins levels, except for HDL, which was significantly elevated. Piperine
      supplementation also improved the plasma levels of apo A-I, T3, T4, testosterone,
      and I and significantly reduced apo B, TSH, and insulin to near normal levels.
      CONCLUSIONS: The data presented here provide evidence that piperine possesses
      thyrogenic activity, thus modulating apolipoprotein levels and insulin resistance
      in HFD-fed rats, opening a new view in the management of dyslipidemia by dietary
      supplementation with nutrients.

PMID- 16910314
TI  - L-ascorbic acid protects the antioxidant defense system in nickel-exposed albino
      rat lung tissue.
AB  - We studied the effect of oral supplementation with L-ascorbic acid (50 mg /100 g
      body weight (BW) on nickel sulfate (2.0 mg/ 100 g BW, i.p)-induced lipid
      peroxidation and histopathology in the lung of Wister strain male albino rats.
      Lipid peroxide and glutathione levels and the activities of the antioxidant
      enzymes, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase
      (GSH-Px), were estimated. Nickel sulfate administration significantly increased
      the level of lipid peroxides and decreased all antioxidant enzyme activities.
      Nickel sulfate treatment also induced (a) loss of normal characteristics and
      architectural organization, (b) inflammation in bronchioles, (c) alveolar
      congestion, (d) alveolar cell hyperplasia, and (e) congestion in the lumen. The
      simultaneous administration of L-ascorbic acid and nickel sulfate improved both
      lipid peroxidation and the histopathology of lung when compared with rats
      receiving nickel sulfate alone. The results indicate that L-ascorbic acid
      prevents nickel-induced alteration of antioxidant defense mechanisms and
      histopathology of lung tissue.

PMID- 16910315
TI  - Health promotion by dietary restriction--a focus.
AB  - Food restriction, although long popular among gerontologists, has emerged as a
      new challenge in public health in postindustrial societies because this is the
      only intervention that repeatedly and strikingly increases maximum life span. The
      practice of food restriction is widespread for cosmetic, health, and economic
      reasons. The beneficial effects and the molecular mechanism of food restriction
      have been well established. The present review summarizes the rapidly
      accumulating evidence on the involvement of food restriction in various diseases
      and focuses on good dietary practices for health promotion in modern life style.

PMID- 16910317
TI  - A validated method for halquinol extraction from chicken liver matrix for
      residual HPLC studies.
AB  - Extraction is the key step in the analysis of food samples, from either plant or
      animal sources for residues of veterinary drugs and pesticides. Such residues
      pose an unacceptable risk to the consumer and information is insufficient to
      allow a full assessment. This paper presents a method for extracting and
      determining Halquinol, a veterinary drug in liver of chicken. The first step of
      the study was to establish and validate a method for determination of Halquinol,
      which was achieved using HPLC equipped with a C18 reversed-phase, monomeric
      column and a MWD-UV detector. In the second step, we extracted and purified the
      liver samples. Liver samples were homogenized in buffer, extracted with ethyl
      acetate, and cleaned up using a solid-phase extraction column. The limit of
      quantification of the method was 0.1 microg/l mL, and detection limit was 0.01
      microg/l mL. Mean recoveries in chicken liver ranged from 57% to 91%.

PMID- 16910316
TI  - Succinic acid monoethyl ester prevents oxidative stress in streptozotocin
      nicotinamide-induced type2 diabetic rats.
AB  - Succinic acid mono ethyl ester (EMS) was recently proposed as an insulinotropic
      tool in the treatment of non-insulin dependent diabetes mellitus. The aim of this
      study was to investigate the effect of EMS on oxidative stress in a
      streptozotocin (STZ)-nicotinamide induced type 2 diabetic model. The EMS was
      injected intraperitoneally at 8 micro mol/g body weight for 30 days. Plasma
      glucose, plasma insulin, thiobarbituricacid reactive substances (TBARS),
      hydroperoxides, superoxide dismutase (SOD), catalase (CAT), glutathione peroxide
      (Gpx), reduced glutathione (GSH), glutathione-S-transferase (GST), and vitamins C
      and E were assayed in liver and kidney. Treatment with EMS and metformin to
      diabetic rats resulted in a significant reduction in plasma glucose, TBARS, and
      hydroperoxides. In addition, the treated groups also showed a significant
      increase in the activities of plasma insulin, SOD, CAT, GPx, GST, GSH, vitamin C,
      and vitamin E in liver and kidney of STZ-nicotinamide-induced diabetic rats. Our
      result suggest that non glucidic nutrient, such as EMS as a potent antidiabetic,
      may optimalize antiperoxidative and antioxidants status by restoring the
      biochemical alterations found in STZ-nicotinamide-induced type 2 diabetes.

PMID- 16910318
TI  - From classroom to Congress. My year on the legislative staff of the U.S. Senate.

PMID- 16910319
TI  - Changing roles in changing world.

PMID- 16910320
TI  - Status of iodine nutriture and universal salt iodisation at beneficiaries levels
      in Kerala State, India.
AB  - Iodine deficiency disorders are an important public health problem in India. It
      is wrongly believed that populations residing in coastal areas do not suffer from
      iodine deficiency as they consume sea foods which are rich in iodine. A high
      prevalence of iodine deficiency has been reported in 11 districts of Kerala
      ranging between 9.3 and 44.5%. In spite of the high prevalence of iodine
      deficiency, the state government of Kerala has not banned the sale of non-iodised
      salt in the state. Thus, the present study was conducted to assess the current
      status of iodine nutriture and level of salt iodisation in Kerala state. The
      study was conducted in all the 14 districts in the state by utilising the uniform
      sampling methodology. A total of 2110 salt samples were collected randomly from
      children. On the spot casual urine samples were collected from 689 children. The
      results revealed that overall 43.8% of the families in the state were consuming
      salt with 15ppm and more of iodine. It was found that three districts namely
      Kasargod, Idukki and Kottayam had median urinary iodine excretion level < 100.0
      microg/l and also more than 20% of the samples had urinary iodine excretion
      levels less than 50 microg/l. The findings of the present study revealed
      continued iodine deficiency amongst the three districts identified as endemic
      earlier. This indicates the need of immediate ban on the sale of non-iodised salt
      for the edible purposes and intensive information, education and communication
      activities for promotion of consumption of iodised salt.

PMID- 16910321
TI  - Spectrum of peripheral neuropathy in eastern India.
AB  - Peripheral neuropathies constitute an important group of disorders in
      neurological practice. Very few systematic studies on peripheral neuropathies are
      available from India. Hence we conducted a prospective study in two large
      hospitals from Kolkata, the biggest city of eastern India in order to find out
      the spectrum of peripheral neuropathy. This prospective study was carried out
      from June 1998 to January 2003 on admitted patients with symptoms and signs of
      peripheral neuropathy. Two hundred and twenty-five patients were evaluated (one
      hundred and twenty-five from an industrial hospital and one hundred from an
      academic tertiary care institution at Kolkata). Result showed that most of the
      cases of peripheral neuropathy belonged to fourth decade with men dominance.
      Common varieties of neuropathy were Guillain-Barre syndrome, diabetes mellitus,
      hereditary motor sensory neuropathy, chronic inflammatory demyelinating
      neuropathy, drugs and toxin related. Unusual varieties were Isaacs's syndrome and
      X-linked hereditary motor-sensory neuropathy. One case of neuropathy due to
      Plasmodium vivax has received intravenous immunoglobulin therapy. The type of
      peripheral neuropathy in hospital-based patients in eastern India was similar to
      other parts of country excepting some sporadic types due to infective or genetic
      causes and a large number of cases of undetermined aetiology exist despite
      detailed investigations.

PMID- 16910322
TI  - Study of biochemical parameters of ascitic fluid in exudative ascites with
      special reference to tuberculous peritonitis.
AB  - In an attempt to differentiate between three important but clinically similar
      conditions of exudative ascites like tuberculous peritonitis, spontaneous
      bacterial peritonitis (SBP) and malignant ascites, we evaluated the biochemical
      parameters of ascitic fluid as a diagnostic aid. The serum ascitic albumin
      gradient (SAAG), lactate dehydrogenase (LDH), pH, adenosine deaminase(ADA),
      carcino-embryonic antigen (CEA) and carbohydrate antigen (CA-125) levels were
      measured in 36 patients with tuberculous peritonitis, 30 patients with SBP and 30
      patients with ascites due to malignant disorders. The LDH level was significantly
      lower in tuberculous peritonitis patients than in malignant and SBP groups. A
      value of < 110 U/l gave the assay a sensitivity of 94% and a specificity of 93%,
      positive predictive value of 89% and negative predictive value of 96% for
      tuberculous peritonitis. The ADA activity was significantly higher in tuberculous
      peritonitis group than in the other two groups. A cut off value > 33 U/l gave the
      ADA test a sensitivity of 89%, specificity of 100%, positive predictive value of
      100 % and a negative predictive value of 94% for tuberculosis. A pH value of
      <7.26 with high SAAG (>11 g/l) predicted SBP with reasonable accuracy. Elevated
      ascitic fluid CEA (>2 ng/ml) and CA - 125(> 35 U/l) was found exclusively in
      cases of malignant ascites with a single case of tuberculous peritonitis showing
      CA-125 value > 35 U/l. All these tests are rapid, non-invasive, and easily
      reproducible and offer good predictive accuracy which is comparable to that of
      more invasive procedures like peritoneoscopy and biopsy.

PMID- 16910323
TI  - Syndromic approach for determination of reproductive tract infections among
      adolescent girls.
AB  - The present study shows overall prevalence (64%) of reproductive tract infection
      among adolescent girls, based on self-perceived symptoms. Mean age of respondents
      were found to be 17.8 +/- 0.82 years and mean age at marriage and mean age at
      first pregnancy were 17.2 years and 17.5 years respectively; 35.35% of girls in
      the present study were married. In addition, no significant difference was
      observed between unmarried (60.10%) and married (71.17%) reproductive tract
      infection groups. Moreover, no significant association was present in prevalence
      of reproductive tract infection between the Muslim (67%) and the Hindu (60%).
      Highest prevalence (84.06%) of reproductive tract infection was observed among
      illiterate girls and with improvement of educational status there was decrease in
      the prevalence and the association was found highly significant. Significantly,
      higher prevalence (72%) was observed among members of family size 7 and above.

PMID- 16910324
TI  - Evaluation of women undergoing sterilisation reversal and subsequent pregnancy
      outcome.
AB  - A total of 114 women underwent sterilisation reversal operation by microsurgical
      technique at Regional Centre of Excellence (RCOE), RG Kar Medical College and
      Hospital, Kolkata from August, 1998 to July, 2000, and follow-up was done for
      next two years. The commonest reason for seeking sterilisation reversal was death
      of male child which was 53.51%. Majority of women (50.88%) were between 25 and 30
      years of age and 86.84% of women were of para 2 or less. Most of the women
      (59.65%) of reversal seeker had undergone prior laparoscopic sterilisation in
      comparison to sterilisation by minilaparotomy (40.35%). It is also seen that 50%
      of them had underwent sterilisation less than 3 years back. Commonest type of
      tubotubal anastomosis performed in this present study was isthmo-isthmic type
      which was 49.12%. Thirty-one patients were lost in follow-up and out of rest 83
      cases, intra-uterine pregnancy was noted in 66.27%. Live birth was 45.78%
      delivered in the same institution, 8.43% of cases had spontaneous abortion and
      3.61% of cases had ectopic pregnancy

PMID- 16910325
TI  - Revascularisation strategy for diabetic multivessel coronary arteriopathy.
AB  - Multivessel diffuse coronary arteriopathy is the hallmark of chronic diabetic
      patients. The ideal method of revascularising this group of patients is
      controversial. This review examines the various modalities available in the
      revascularisation of coronary artery disease in diabetic patients. Various trials
      have been conducted to compare the effectiveness of surgical and percutaneous
      methods of revascularisation. Most of the important trials like BARI, CABRI,
      EMORY and Duke's database are critically analysed and a meaningful practical
      strategy to manage this difficult subgroup of patients is outlined. The
      recommendations may change after a few years if the new coated stents prove their
      worth.

PMID- 16910326
TI  - Peri-operative anaesthetic management of neonates for surgical emergencies.
AB  - Surgery of neonates can be fraught with hazards unless the anaesthesiologist is
      conversant with the physiologic and pharmacologic responses under anaesthesia and
      surgery. The principles of anaesthetic management for surgery of critically ill
      neonates with common congenital malformations are briefly discussed in this
      article.

PMID- 16910327
TI  - Primary testicular lymphoma--A case report.
AB  - Primary lymphoma of the testis is more commonly seen in the elderly age group. A
      45-year-old Hindu male with histopathological diagnosis of non-Hodgkin's lymphoma
      of the right testis presented after orchiectomy of the right testis. The patient
      was put on two cycles of chemotherapy consisting of cyclophosphamide,
      vincristine, adriamycin and prednisolone at 3- weekly interval followed by
      external radiation therapy. During follow-up after 7 years he developed left
      facial nerve palsy and left sided haemiparesis. On CT scan of the brain multiple
      space occupying lesions were seen in both the hemispheres of the brain. He was
      put on cranial radiation therapy with intrathecal methotrexate injections. He
      responded favourably with the treatment.

PMID- 16910328
TI  - Moyamoya disease--magnetic resonance imaging and magnetic resonance angiographic
      features.
AB  - A rare case of moyamoya disease in a 9-year-old female presented with behavioural
      disturbances and recurrent hemiparetic attacks is reported. Moyamoya disease is
      an uncommon form of arteritis which affects the cerebrovascular circulation.
      Magnetic resonance angiography is a non-invasive technique for evaluation of the
      carotid and vertebrobasilar circulation. The magnetic resonance angiography
      findings are typical and characteristic of this disease.

PMID- 16910329
TI  - Efficacy of a fixed dose combination of diclofenac sodium and acetaminophen
      (Rhumacort) injection in postoperative pain.
AB  - To evaluate the efficacy and safety of a fixed dose combination of diclofenac
      sodium and acetaminophen injection a study was carried out in patients suffering
      from acute pain. Thirty-eight adult patients undergoing orthopaedic surgery
      received 3ml injection of diclofenac 25mg and acetaminophen 75mg per ml by deep
      intramuscular route 8 hourly for 6 doses. The pain assessment was made on a 1-100
      mm visual analogue scale (VAS), onset of action, extent of pain relief and
      maximum fall in VAS score after the first dose was assessed. Injection
      pentazocine lactate was administered as rescue medication in case of uncontrolled
      pain. At baseline the pain score on VAS was 78.55 +/- 17.12, which at the end of
      1 hour was found to be 43.57 +/- 19.91. There was a statistically significant
      (p<0.0001, ANOVA) reduction in mean pain score starting from 15 minutes after
      administration of first dose and extending up to the end of study period.
      Complete relief was seen in 17 patients (44.74%) and the mean time for complete
      relief was 172.20 minutes after the first dose. Maximum fall and maximum
      percentage fall in VAS score during the study period was 71.71 mm and 92.76%
      respectively on a 0-100 mm VAS, and the time for achieving maximum fall was
      172.50 minutes after the first dose of study medication. The results of this
      study suggest that fixed dose combination of diclofenac and acetaminophen is
      effective and safe for management of postoperative pain in orthopaedic surgery.

PMID- 16910330
TI  - Bird flue to human influenza--present reality for a future pandemic.

PMID- 16910331
TI  - Vaginal birth after one caesarean section: analysis of indicators of success.
AB  - A study was carried out among 81 women with previous one caesarean section (CS)
      done for non-recurrent indications to confirm the efficacy and safety of trial of
      labour (TOL) and to examine the effect of various factors on the mode of
      delivery. Singleton term pregnancy, vertex presentation and adequate pelvic
      capacity were the pre-requisites for case selection. Careful monitoring was done
      during labour and effect of various factors on the outcome was analysed
      statistically. Success rate of TOL was 73%. A non-recurrent indication for
      previous CS, such as malpresentation and foetal distress is associated with
      higher success rate of vaginal birth after caesarean (VBAC) compared to recurrent
      indications, such as cephalopelvic disproportion (CPD) and failure to progress
      (FTP). Prior vaginal birth improves the success rate (87%) of VBAC. Factors like
      premature rupture of membranes, hypertensive disorders of pregnancy, and post
      date pregnancy did not affect the outcome adversely. Rate of emergency CS was 44%
      in women with floating head foetus, 39% in induction/augmentation group and 43%
      when birth weight of the foetus was > 3000 g. No maternal/perinatal mortality
      observed. Maternal/perinatal morbidity was low in cases with successful TOL.
      Uterine rupture occurred in one woman. There are few absolute contra-indications
      to attempted VBAC. Though the success rate does vary with different pre-existing
      factors, the clinician may anticipate greater than 50% chance for success in any
      individual labour.

PMID- 16910332
TI  - Evaluation of visual outcome following cataract surgery in a tertiary eye care
      hospital.
AB  - A retrospective study was conducted at the Regional Institute of Ophthalmology
      (RIO), Kolkata to assess the visual outcome in senile cataract after surgery in
      the age group of 45-65 years. A total number of 1837 operated eyes (1826
      patients) were included in the study during the period of January, 2000 to
      December, 2000. Patients with low vision unrelated to cataract surgery were
      excluded. The mean age at cataract extraction was 56 +/- 9 years. Patients were
      followed for 6 months. Of 1837 operated eyes, 26 (1.4%) were blind (visual acuity
      < 3/60), 122 (6.6%) had low visual acuity (3/60-6/18) and 1689 eyes (92.2%)
      gained good vision (visual acuity > 6/18). Of 148 visually compromised eyes
      posterior capsular opacity (41.2%) was the commonest complication followed by
      corneal oedema (36.5%) and glaucoma (12.8%). Other posterior segment causes
      accounted for the remaining cases. The study emphasises the need for proper
      selection, good pre-operative check-up, skilled surgery and regular follow-up to
      improve the qualitative aspect of cataract surgery.

PMID- 16910333
TI  - Simultaneous continuous ambulatory peritoneal dialysis catheter implantation and
      inguinal hernia repair.
AB  - Continuous ambulatory peritoneal dialysis is a new modality of treatment for end
      stage renal disease. Although this procedure is largely underutilised in India,
      in Manipur this procedure is routinely offered to patients of end stage renal
      disease. Continuous ambulatory peritoneal dialysis catheter implantation was
      started in Manipur in May, 2001. Till now continuous ambulatory peritoneal
      dialysis catheter has been implanted in 116 cases. Out of this 3 patients had
      associated inguinal hernia. Inguinal hernia is a relative contra-indication for
      continuous ambulatory peritoneal dialysis. Still the inguinal hernia was repaired
      in the same sitting with the catheter implantation. The procedure is described
      along with the outcome.

PMID- 16910334
TI  - Female infertility: role of vaginal hormonal cytology, endometrial biopsy and
      endocrinological evaluation.
AB  - Female infertility can be categorised into those who fail to ovulate (anovulatory
      infertility) because of some defect at hypothalamic-pituitary-ovarian axis and
      those who are ovulatory (ovulatory infertility), but are infertile because of
      some lesion present in genital tract. The role of vaginal hormonal cytology,
      endometrial biopsy and endocrinological evaluation in the detection of ovulation
      and various ovulatory dysfunction was studied in 42 infertile female patients. On
      the basis of cytological findings, of the 42 patients, 14 were found to be
      ovulatory, 26 anovulatory (which include 5 cases of atrophic changes) and 2
      inconsistent due to inflammatory changes. Endometrial biopsy showed evidence of
      ovulation in 15, anovulation in 27 cases. Hormonal evaluation indicated some sort
      of endocrinological disorders in 15 patients, which may underlie anovulatory
      infertility in these patients, while results were within normal range in the rest
      27 patients. Results of vaginal cytology and endometrial biopsy showed
      correlation in respect to ovulation in 93.33% of the cases.

PMID- 16910335
TI  - No scalpel vasectomy--an overview.
AB  - Male sterilisation is less popular because of fear of loss of virility and loss
      of physical strength. No scalpel vasectomy is a surgical attempt to reduce
      complications and thereby allays the fear in the minds of the couples. Despite
      the introduction of the advanced technique the acceptance of male sterilisation
      has not gone up. Though with aggressive IEC compaign has failed to produce the
      desired result, but a camp based approach was successfully adopted in some states
      of India. Technique of no scalpel vasectomy has been summarised in the article
      with diagrams. Some postoperative instructions should be given to the client
      after discharge. No scalpel vasectomy is the gold standard for vasectomy today.
      Training is mandatory for experienced surgeons. Government of India funds and
      supports both the training and service activity.

PMID- 16910336
TI  - No scalpel vasectomy advocacy and community mobilisation--a personal experience.
AB  - The so called myths and taboos among the people of India are obstactes
      controlling population explosion and thereby the nation is being handicapped with
      economic development. To propagate awareness and information, the NSV Resource
      Center took up organising mega camps for the acceptance of NSV as the method of
      family planning and male participation. The awareness material has been developed
      to bring forth total sociocultural transformation through development of intense
      desire, strong determination, effective management and inclusion of a zeal of
      perpetual efforts both among the promoters and acceptors. The information modules
      have been developed to suit the requirements of various vehicles through which
      the message has to be spread. Awareness messages are generated through the inputs
      from sociocultural, economic, ethical, hygienic and administrative acumen. The
      materials prepared are disseminated through display hoardings, wall writings,
      distribution of pamphlets, audiovisual clips, face to face counselling, etc.
      Communication technology serves mobilising and educating people, especially rural
      populace. Some steps are suggested to reach remotest villages which are
      elaborated. Counselling is an essential part of motivation to the client. During
      the last 5 years a significant surge has been noticed in terms of access to new
      communication technologies. This may be employed to successfully implement the
      family planning programme.

PMID- 16910337
TI  - Community ophthalmology--an approach including tentative strategic interventions
      in brief.
AB  - Community ophthalmology is based mainly on the principles of primary healthcare
      approach with active community involvement and participation, focus on
      prevention, equity of distribution of resources, involvement of correct and
      recent technological procedures and integrated multisectoral approach. In our
      country National Programme for Control of Blindness was launched in 1976.
      Community ophthalmology programme can play definitely a great role there.

PMID- 16910338
TI  - Leiomyosarcoma of uterus--a case report.
AB  - Leiomyosarcoma of uterus is a very rare malignant mesenchymal tumour of uterus.
      It may arise from the uterine myometrium de novo or may be transformed from a pre
      existing benign leiomyoma. A 55-year-old female presenting with 20-22 weeks size
      of uterus and bleeding per vagina was clinically diagnosed as a case of leiomyoma
      uteri and cervical polyp, was subjected to abdominal hysterectomy. The tumour
      mass was later confirmed histologically as leiomyosarcoma of uterus presumed to
      be transformed from pre-existing leiomyoma uteri.

PMID- 16910339
TI  - Non-resolving pneumonia in a young boy--beware of foreign body aspiration.
AB  - A 4 1/2-year-old boy presented with recurrent cough and cold of 2 years duration.
      Chest x-ray revealed collapse consolidation of right lower lobe. Rigid
      bronchoscopy was done and the nozzle of a pen was extracted from right main
      bronchus. The radiological improvement took three months after extraction of the
      foreign body. Undetected foreign body aspiration is one of the causes of
      nonresolving pneumonia in children.

PMID- 16910340
TI  - Adrenal myelolipoma--report of a case.
AB  - Adrenal myelolipoma is a rare, benign, non-secreting tumour composed of adipose
      and haematopoietic tissue. One such rare case in a 32-year-old female who
      presented with'pain in right lumbar region is reported here. CT scan revealed a
      mass in the suparenal region measuring 5.6 x 5 cm. In view of the size and
      symptomatic nature of the mass, surgical resection was performed. Histological
      examination revealed the features of myelolipoma. The outcome was favourable
      without recurrence after a follow-up of one year.

PMID- 16910341
TI  - Hydrocele of the canal of Nuck.
AB  - Hydrocele of the canal of Nuck is an uncomon and infrequently reported finding in
      women. A 24-year-old female presented with a painless left groin swelling which
      was soft, cystic, non-tender with 7.5 cm x 5 cm in measurement. It was more
      prominent in standing. Ultrasonography revealed an encysted echofree lesion in
      the left inguinal canal. On surgery, a cyst was found containing clear fluid in
      the inguinal canal which was dissected out and wound was closed in layers. The
      patient is doing well till date. Here one such case with diagnosis of hydrocele
      of the canal of Nuck is reported.

PMID- 16910342
TI  - Prevalence of hepatitis TT virus DNA among the voluntary blood donors: a sunmary
      from some previous studies.

PMID- 16910343
TI  - B cell lymphoma masquerading as recurrent tonsillitis with necrotising
      lymphadenitis (Kikuchi's disease).

PMID- 16910344
TI  - Curcumin protects mouse brain from oxidative stress caused by 1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine.
AB  - We tested the hypothesis that curcumin, a polyphenolic antioxidant, acts as a
      powerful free radical scavenger in vivo in the brain, and interferes with
      oxidative stress caused by the parkinsonian neurotoxin, (MPTP) 1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine. We measured the (GSH) reduced glutathione levels,
      (TBARS) glutathione lipid peroxidation, (CAT) catalase and (SOD) superoxide
      dismutase activity in the (ST) striatum and (MB) mid brain 3rd day and 7th day
      following MPTP and curcumin administration. MPTP treatment caused a significant
      depletion in GSH and increased the specific activity of SOD, CAT and lipid
      peroxidation in both ST and MB on the 3rd and 7th day. MPTP induced GSH depletion
      and lipid peroxidation in ST and MB was blocked by curcumin treatment. Curcumin
      exhibited a synergistic effect on SOD and CAT activities in the ST and MB
      regions. The present study provides direct evidence for the involvement of
      curcumin in neuroprotection against oxidative stress.

PMID- 16910345
TI  - The multi-face expression of familial Mediterranean fever in the child.
AB  - Familial Mediterranean fever (FMF) is characterized by recurrent self-limiting
      flares of fever in the absence of pathogens, autoantibodies or antigen specific T
      cells and is inherited as an autosomal recessive trait probably deriving from
      common ancestors of Armenian, Jew, Turk and Arab origin. The underlying
      pathogenetic mechanisms of FMF have not been fully interpreted, but mutations in
      the gene MEFV encoding pyrin, a natural repressor of proinflammatory molecules,
      result in uncontrolled relapsing systemic inflammation, increased leukocyte
      migration to serosal membranes or joints and inappropriate response to
      inflammatory stimuli. FMF heterogeneous phenotypic expression could originate
      both from allelic heterogeneity or from the existence of modulating genes. Proper
      diagnosis of FMF is needed to begin both specific clinical management and
      treatment based on continuous prophylactic administration of colchicine,
      preventing flares or at least the onset of amyloidosis.

PMID- 16910346
TI  - The pharmacologic basis of treatment with colchicine in children with familial
      Mediterranean fever.
AB  - Familial Mediterranean fever (FMF) is the prototype of auto-inflammatory
      disorders and is ethnically restricted to people living in the Mediterranean
      basin and Middle-East. Pyrin, the protein product of the FMF gene, expressed in
      myeloid cells and fibroblasts, interacts with the cytoskeletal machinery and may
      modulate leukocyte effector functions. At present colchicine, an alkaloid with
      antimitotic activity interfering with microtubule formation, which has been used
      to alleviate acute gout, is the only available drug for patients with FMF to
      prevent both acute attacks and long-term complications such as amyloidosis. The
      anti-inflammatory effect of colchicine may be mediated not only through direct
      interaction with microtubules, but also through changes at the transcriptional
      level influencing cell cycle regulation and leukocyte migration. Gastrointestinal
      side effects may occur early and are the most frequent manifestations of
      colchicine toxicity in children, whilst multiple organ failure is very rarely
      reported as overdosage expression.

PMID- 16910347
TI  - Palliative treatment of upper gastrointestinal obstruction using self-expansible
      metal stents.
AB  - Gastric outlet obstruction is either a late event in the natural history of bilio
      pancreatic tumors or the result of recurrent gastric or pancreatic tumors. Self
      expansible metal stents, inserted under endoscopic and fluoroscopic control, can
      be used for palliative treatment. The present study was aimed at evaluating both
      the feasibility and the results of stenting in patients with malignant gastric
      outlet obstruction; in addition, some technical suggestions are presented. A
      total of 33 patients, who had a metal stent positioned, were retrospectively
      evaluated; 20 of them were women and 13 were men, aged from 45 to 94 years, with
      a mean age of 75 years. Twenty-seven patients had a pancreatic adenocarcinoma, 4
      had a stricture of a gastrojejunal anastomosis due to recurrent pancreatic tumor,
      2 had a stricture of a gastrojejunal anastomosis secondary to gastric cancer
      surgery. No postoperatory complications were observed. Improvement in the quality
      of life was obtained in all patients. Following the stenting procedure, the
      median duration of hospitalization was 8 days (range: 6-20 days), and the mean
      survival rate was 12 weeks (range: 2-66 weeks). Endoscopic stenting for the
      palliation of malignant gastric outlet obstruction is feasible and is well
      tolerated by most patients. In some cases a period of enteral nutrition had to be
      necessarily carried out; nonetheless, the insertion of the stent improved the
      quality of life.

PMID- 16910348
TI  - Prevalence of HCV antibodies in autoimmune thyroid disease.
AB  - BACKGROUND AND OBJECTIVES: Auto-immune thyroid disease (AITD) has often been
      reported during interferon-alpha therapy for chronic viral C hepatitis (HCV) or
      other diseases. Recently, a high AITD prevalence has been reported in HCV
      independently on alpha-interferon therapy. The aim of our study is to investigate
      the possible relationship between AITD and HCV and HBV virus infections, and
      their influence on the thyroid function. MATERIAL AND METHODS: We prospectively
      studied 112 patients with AITD (94 women and 18 men; mean age: 49.8 +/- 14.9 yrs)
      and 88 patients with non-toxic goitre (NTG) (73 women and 15 men; mean age: 50.2
      +/- 13.5 yrs) as controls. In all patients HCV antibodies, HBsAg and anti-HBs
      antibodies, TSH, FT3 and FT4 serum levels, circulating anti-thyroid-peroxidase
      antibodies (TPO-Ab) and anti-thyroglobulin antibodies (TG-Ab) were measured.
      RESULTS: HCV antibodies were positive in 11.6% of AITD patients (13/112) and in
      2.3% of controls (2/88) (P < 0.05), the prevalence of HCV in the controls being
      similar to the expected value in the general population (about 2%). HBsAg and
      anti-HBs were found only in 2.6% of AITD patients (3/112) and 1.1% of controls
      (1/88) (P = NS), according to the expected value in the general population (about
      2.5%). No difference in thyroid function was observed between positive and
      negative HCV subgroups. CONCLUSION: A significant association between HCV
      infection and AITD was found. This finding confirms that HCV, but not HBV, could
      be one of the environmental factors responsible for the breakdown of
      immunological tolerance. Therefore detection of TPO-Ab and TG-Ab in all HCV
      patients, independently of IFN therapy, is suggested and the utility of a
      screening for HCV in all AITD patients is stressed.

PMID- 16910349
TI  - Total thyroidectomy in amiodarone-induced thyrotoxicosis. Preoperative,
      intraoperative and postoperative considerations.
AB  - A female patient was admitted to our Department for total thyroidectomy in
      amiodarone-induced thyrotoxicosis. The drug was prescribed for ventricular
      arrhythmia and atrial paroxysmal fibrillation in dilated cardiomyopathy due to
      chronic aortic regurgitation with left ventricular dysfunction (ejection fraction
      35%; Class Functional NYHA III) and moderate-severe respiratory insufficiency.
      The cardiologist-anesthetist team has allowed to evaluate the surgical
      cardiovascular-anesthesiologic risks and the balance between the improvement by
      the amiodarone administration for the arrhythmia, and the discontinuation of this
      treatment in order to prevent aggravation of the thyrotoxicosis. These hypotheses
      were subsequently discharged for the two reasons listed below: - several other
      antiarrhytmic drugs (that didn't show equivalent efficacy as amiodarone in
      preventing or converting such ventricular and atrial arrhythmias) may be proposed
      in the place of amiodarone. However, this could expose the patient to an
      arrhythmia; - a clear proof that the suspension of amiodarone can allow restoring
      normalization of the thyroid function doesn't exist. Therefore, the patient has
      been successfully submitted to the surgical intervention and in the follow-up we
      brought her back to a state of normalized thyroid function and cardiovascular
      conditions. In patients that cannot safely discontinue amiodarone or when medical
      therapy is ineffective in controlling thyrotoxicosis, thyroidectomy is the
      treatment of choice.

PMID- 16910350
TI  - Body composition analyses in normal weight obese women.
AB  - The purpose of this study was to identify new indexes of body composition that
      characterize the normal weight obese (NWO) women. We measured body composition by
      dual energy x-ray absorptiometry (DXA) and resting metabolic rate (RMR) by
      indirect calorimetry in a cohort of seventy-five healthy Italian women,
      subdivided into three groups (nonobese/controls, NWO, preobese-obese women).
      Despite a normal body mass index (BMI), the NWO women have a higher body fat mass
      percentage (FAT %) (38.99 +/- 6.03) associated to a significant (p = 0.02) lower
      amount of lean mass of legs (12.24 +/- 1.31) and lean mass of left leg (6.07 +/-
      0.64) with respect to the control group. The NWO group showed a significant (p =
      0.043) lower RMR (1201.25 +/- 349.02) in comparison with nonobese and preobese
      obese women. To classify NWO individuals among general population, we identified
      three significant body composition indexes: abdominal index, leg index and trunk
      index. The NWO women showed significant increased value in the three indexes (p <
      0.001). Our results suggest that, despite a normal BMI, the NWO women displayed a
      cluster of anthropometric characteristics (body fat mass percentage, leg indexes)
      not different to obese women ones. An appropriate diet-therapy and physical
      activity may be protecting NWO individuals from diabetes and cardiovascular
      diseases associated to preobese-obese women.

PMID- 16910351
TI  - Benefits and concerns associated with biotechnology-derived foods: can additional
      research reduce children health risks?
AB  - The development of techniques devised for the genetic manipulation of foods poses
      new risks for children with food allergy (FA). The introduction of foreign
      allergenic proteins from different foods into previously tolerated foods may
      trigger allergic reactions, often complicating with anaphylactic shock in a
      subset of allergic babies. Children with FA, even if subjected to preventative
      diets, always challenge the risk of developing allergic manifestations after
      unintentional intake of a non tolerated food in restaurant settings, with
      relatives or schoolmates, etc, where product labelling is necessarily lacking.
      The introduction of potentially allergenic proteins into foods generally
      considered safe for allergic children can be done deliberately, by either
      substantially altering the food ingredients, or by genetic manipulation which
      change the composition or transfer allergens, or unintentionally by quality
      control failures, due to contaminations in the production process, or to genetic
      mismanipulation. There is a controversy between multinationals often favored by
      governments and consumer association resistance, thus an equidistant analysis
      poses some unprecedented impediments. The importance of FA and the potential of
      transgenic plants to bring food allergens into the food supply should not be
      disregarded. The expression in soybeans of a Brazil nut protein resulted in a
      food allergen expressed in widely used infant formulas, so paving the way to an
      often reported multinational debacle. Genetic engineering poses innovative
      ethical and social concerns, as well as serious challenges to the environment,
      human health, animal welfare, and the future of agriculture. In this paper will
      be emphasized practical concepts more crucial for pediatricians.

PMID- 16910352
TI  - Dermal apoptosis is not influenced by the severity of clinical conditions in
      burned patients.

PMID- 16910353
TI  - [In situ carcinomas of the breast: clinical features and therapeutic strategies].
AB  - INTRODUCTION: Lobular and ductal carcinomas in situ of the breast (LCIS and DCIS)
      origin from the ductal-lobular unit of mammary gland, but they are characterized
      for different morphologic patterns and evolution. In 1980 they represent 1.4% of
      diagnosis in breast biopsy, less of 5% of carcinomas of the breast. Actually in
      7.5% of breast biopsy an in situ carcinoma is recognized (approximating 40% of
      breast cancers). Our purpose is to evaluate the different available strategies in
      the clinic management of DCIS and LCIS and, in case of surgical treatment, which
      reconstructive approach obtains satisfactory breast conformation. MATERIALS AND
      METHODS: The study enclose 125 patients: 40 of them presented LCIS (32%) and 85
      DCIS (68%). In 40 patients (32%) underposed to mastectomy was performed a
      reconstruction in cooperation with aesthetic surgeons. 35 of 40 women with LCIS
      are included in a follow-up programme, 5 of them had a bilateral mastectomy and
      reconstruction. RESULTS: No recurrences were observed in patients affected by
      LCIS. Six patients underposed to wide excision for DCIS developed local
      recurrence, treated by mastectomy. No recurrences were observed in patients
      treated initially with mastectomy. Some complications correlated to
      reconstruction were detected. CONCLUSIONS: One of most controversial sights in
      breast pathology is the understanding of biological meaning of CLIS: in facts
      CDIS can be considered a pre-invasive cancer, CLIS is reasonably considerable
      only a risk indicator for developing breast cancer but it isn't a pre-neoplastic
      lesion. Very important is the reconstruction of the breast to improve the quality
      life of patients.

PMID- 16910354
TI  - The sentinel lymph node in papillary cancer of the thyroid including histological
      subtype.
AB  - BACKGROUND: The aim of this work was to reveal through sentinel node study the
      intraoperative presence of preoperatively undetected pathological lymph nodes.
      MATERIALS AND METHODS: At the Surgical Science Department of La Sapienza
      University of Rome The Authors studied from January 2003 to June 2004 18 patients
      with papillary carcinoma of the thyroid, who presented no clinical evidence of
      lymph node metastasis; they performed a total thyroidectomy in all cases,
      removing and histologically examining all lymph nodes of the upper anterior
      mediastinum. Where negative they were then subjected to immunohistochemical
      analysis with Pan Cytokeratin. RESULTS: The method was positive in 10 patients: 2
      pure papillary carcinomas, 1 papillary carcinoma with poorly differentiated
      areas, 1 tall cell papillary carcinoma, 5 sclerosing carcinoma and 1 follicular
      variant papillary carcinoma; and negative in 8:5 pure papillary carcinomas, 2
      sclerosing carcinoma and 1 case of follicular variant papillary carcinoma. Lymph
      node micrometastasis was found in 2 cases through study with Pan Cytokeratin on
      final histological examination. CONCLUSIONS: Analysis of the Authors' preliminary
      data shows that sentinel lymph node detection has 83.3% sensitivity and 100%
      specificity for Upper Anterior Mediastinum lymph nodes. The Authors can propose
      two main applications: select for dissection only patients with a positive
      sentinel node and reduce the number of cases to be subjected to postoperative
      treatment with iodine ablation, in patients with "low risk" thyroid tumours and
      negative sentinel nodes.

PMID- 16910355
TI  - [Biliary stent placement for postoperative benign bile duct stenosis: personal
      experience].
AB  - OBJECTIVE: To describe the management and outcome after endoscopic treatment of
      23 patients with post-operative benign bile duct stricture (BBDS) managed in
      Authors' Department from 1991 to 2000. BACKGROUND DATA: The management of the
      postoperative bile duct strictures remains a challenge for even the most skilled
      biliary tract surgeon and endoscopist. The 1990s saw a dramatic increase in the
      incidence of bile duct strictures from the introduction and widespread use of
      laparoscopic cholecystectomy. The management of these injuries, short-term
      outcome and follow-up have been reported. METHODS: Data were collected
      retrospectively on 23 patients treated in the Service of Diagnostic and Operative
      Endoscopy of the Operative Unit of General and Thoracic Surgery (Policlinico
      Paolo Giaccone, Palermo, Italy) with BBDS between 1991 and 2000. All patients
      underwent ERCP (endoscopic retrograde cholangiopancreatography). Follow-up and
      pharmacological therapy post-ERCP were conducted by scheduled medical audit.
      RESULTS: Of the 23 initial patients, 20 undergoing endoscopic stenting (3 with
      complete transaction were invited to surgery), 16 had completed treatment with
      symptoms resolution (mean follow-up of 70 months). One patient died of reason
      unrelated to biliary tract disease before the completion of treatment. Seven had
      not completed treatment. Of 16 patient who had completed treatment, 13 were
      considered to have a successful outcome without the need of follow-up invasive,
      diagnostic or therapeutic interventional procedures. Overall, a successful
      outcome, was obtained in 65% of patients, including those requiring a secondary
      procedure for recurrent strictures. CONCLUSIONS: Postoperative bile duct
      strictures remain a considerable surgical challenge. Management with endoscopic
      cholangiography to delineate the postoperative anatomy and to place biliary
      stents, to solve the symptoms, is associated with a successful outcome in up of
      65% of patients, in well experienced team. Endoscopic treatment should be the
      initial management of choice for postoperative bile duct stenosis, as a real
      alternative to surgical reconstruction: because his failure will not compromised
      the following surgical treatment prior endoscopic treatment does not preclude
      surgery), whereas endoscopic treatment is impossible one a Roux-en-Y loop has
      been constructed

PMID- 16910356
TI  - [The surgical treatment of neoplastic colorectal occlusions].
AB  - The emergency treatment for neoplastic occlusions of rectum still needs
      debugging. While we finds perfect accord in to directly treat with a right
      hemicolectomy (more or less widened) the tumours from cecum to the first portion
      of the right colon, not the indications are likewise shared in presence of
      neoplastic stenosis of sigma-rectum. The treatment of urgency of these tumours is
      lent to so many variable and the tendencies too are constantly in evolution in
      relationship to the improvement of the technologies and the surgical devices. We
      have to chose from the two-three times intervention (now with less succession),
      or the total or subtotal colectomy otherwise the most used left hemicolectomy and
      anterior resection for sigmoid colon. Presenting our historical cases of 31 years
      of activity (Institute of Surgical Emergency Department--University La Sapienza
      of Rome), 564 neoplastic occlusions of the colon (75.7% sigma-rectum), the
      Authors describe their attitude both of approach and of surgical therapy in
      urgency that has brought them to practise in the 65.6% of the cases the anterior
      resection without protection colostomy, with extraperitoneal anastomosis and
      reconstitution of the pelvic peritoneum, in all the stenosis under descendant-
      sigma. In the last period it is frequent more and more the tendency to the
      positioning of a stent on the neoplastic stenosis: this treatment allows us to
      overcome the emergency to operate then under fitter conditions.

PMID- 16910357
TI  - [Mainly abdominal "complex" polytrauma. Considerations on surgical strategy and
      clinical case report].
AB  - The Authors want to present un uncommon case of polytrauma managed with surgical
      treatment at the Trauma Center of the A. Cardarelli Hospital in Naples. Chest,
      abdomen, pelvis, and left lower limb have been severely injured. This case is so
      interesting because of the rareness of some lesions (i.e. diaphragm rupture) and
      the numerous lesions of internal organs (i.e. lungs, spleen, liver, pancreas,
      mesenterium) and of the bones (i.e. thigh-bone and pelvis). A very good outcome
      has been obtained for survival as well as for functionality and quality of life
      since we have strictly applied the rules for the management of the "complex"
      polytrauma.

PMID- 16910358
TI  - A prospective comparison of endorectal ultrasound and pelvic magnetic resonance
      in the preoperative staging of rectal cancer.
AB  - BACKGROUND: The development of new surgical modalities (local excision, coloanal
      anastomosis) and the diffusion of preoperative neoadjuvant therapy, has increased
      the importance of an accurate preoperative staging in patients with rectal
      cancer. The aim of this study was to compare the accuracy of endoscopic
      ultrasound (EUS) and magnetic resonance imaging (MRI) in the local preoperative
      staging of rectal carcinoma; moreover the two methods were assessed with a
      concordance K test. METHODS: Twenty-nine patients with rectal carcinoma were
      staged with EUS and body coil MRI and then underwent radical surgery. The
      preoperative staging was compared with the histologic findings of the operative
      specimen. RESULTS: EUS was more accurate (79.3%), with better sensibility (90%),
      positive predictive value (PPI9 (85.7%) and negative predictive value (NPV) (25%)
      than MRI in the evaluation of T parameter. MRI was more accurate (72.4%), with
      better specificity (81.2%), PPV (72.7%) and NPV (68.4%) than EUS in the
      evaluation of N parameter. The concordance test obtained a K value of 19.8% for
      the T parameter and 34.2% for the N parameter. CONCLUSIONS: EUS and MRI are
      complementary methods in the preoperative staging of rectal cancer. EUS is more
      accurate in determining bowel wall penetration of the tumor, while MRI is more
      accurate in the evaluation of lymph node involvement. The low value of the K
      index confirms the complementarity of the two examinations. Further studies with
      new imaging techniques such as endocoil MRI, external phase-arrayed coil MRI and
      three dimensional ultrasound are needed to identify the most effective single
      examination in the preoperative staging of rectal cancer.

PMID- 16910359
TI  - [Haemorrhoidectomy according to Ferguson in day-surgery. Experience and results].
AB  - AIM OF THE STUDY: To evaluate of results of 1511 surgical haemorrhoidectomies
      performed in day-surgery setting (7-24 hours hospital stay) with improvement of
      both cost effectiveness and patient comfort. MATERIAL AND METHODS: From January
      1980 to December 2002, 1511 patients underwent haemorrhoidectomy according to
      Ferguson, 1011 patients for grade III-IV haemorrhoids 10% of them for recurrence
      and 5% previous treated by cryotherapy or elastic ligature, 500 patients for
      grade II haemorrhoids 25% of them previous treated by cryotherapy or elastic
      ligature and 7% for recurrence. 97.6% of patients were operated on with loco
      regional anaesthesia; the others with narcosis and peripheral anaesthesia. The
      hospital-stay was 24 hours in 34% of patients, while the remaining 66% operated
      on under loco-regional anaesthesia were hospitalised for 7-10 hours. Twenty-seven
      patients (1.8%) have had postoperative haemorrhage, only three patients (0.2%)
      underwent reoperation under general anaesthesia with a hospital stay of 7 days.
      In 52% of patients clinical recovery was observed at first follow-up (7 days);
      48% had recovered at the second follow-up (14 days). RESULTS: In 1286 patients
      (98% of patients came back to control) anatomical recovery was observed at the
      follow-up three months after surgery. Patients satisfaction 6 months after
      operation was high in 73%; good in 26%; low in 1%. CONCLUSIONS: These results
      seems confirm the feasibility of haemorrhoidectomy in day-surgery in almost all
      patients, with both a considerably cost reduction and enhanced patient comfort
      and compliance.

PMID- 16910360
TI  - [Lichtenstein vs. Rutkow-Robbins technique in the treatment of primary inguinal
      hernia. Analysis of the long term results].
AB  - BACKGROUND: The AA. compared the preliminary results of two different methods of
      inguinal hernioplasty: one using only the mesh (Lichtenstein) and the other one
      using both mesh and plug (Rutkow-Robbins). PATIENTS AND METHODS: Seventy
      consecutive patients were randomly allocated into two groups, 35 patients each
      one, to receive either a Licthenstein mesh or a Rutkow-Robbins plug and mesh for
      primary monolateral groin hernia. RESULTS: Follow-up was planned at 1 week, 3
      weeks, 3 and 6 months after surgery. The Authors evaluated early and late
      complications i.e.: the presence of paraesthesia, postoperative pain and the
      incidence of recurrence. The results were analysed statistically using the Fisher
      and chi2 tests. CONCLUSIONS: Data parameters did not show statistically
      significative differences between the two groups (p > 0.05). No recurrences were
      detected. The Authors concluded that no advantage may derivate by an additional
      plug to the single mesh hernia repair.

PMID- 16910361
TI  - Paraesophageal hernia in childhood.
AB  - AIM OF THE STUDY: Paraesophageal hernia is a particularly rare condition in
      childhood. Sometimes it is possible to have an asymptomatic course and to be
      discovered incidentally. Anyway there are no more than 20 reported cases of which
      only two are well studied and documented to be real paraesophageal hernias. CASE
      REPORT: Patients were all over 4 years old except for our little patient which
      was 18 months old, the only infant reported with this condition. On the contrary
      it is the most common postoperative complication of Nissen fundoplication, which
      is the most commonly performed, surgical technique for the correction of
      gastroesophageal reflux in children. CONCLUSIONS: The Authors believe that the
      presentation of this case with all its special characteristics will improve
      knowledge about this rare entity and add information about its treatment and
      surgical correction that are use full for all doctors that care children.

PMID- 16910362
TI  - Gastric outlet obstruction due to inflammatory fibroid polyp.
AB  - INTRODUCTION: Inflammatory fibroid polyp (IFP) is a rare mesenchymal tumor of the
      gastrointestinal tract. The lesion is characterized by spindle-shaped stromal
      cells and an inflammatory infiltrate rich in eosinophils. CASE REPORT: The AA.
      present a case of the IFP of the stomach. A 85-year-old woman was admitted to the
      hospital for early vomiting and epigastric pain. The patient underwent a
      gastroduodenoscopy that revealed a polypoid lesion mimicking cancer of the antrum
      and subtotal obstruction of the gastric transit. CONCLUSIONS: The Endoscopic
      Ultrasound Sonography suggested the presence of a lesion of the submucosal layer
      such as lymphoma or other type of malignancy like gastrointestinal stromal tumor
      (G.I.S.T).

PMID- 16910363
TI  - [Small bowel intussusception caused by metastasis from anaplastic thyroid
      carcinoma: case report and literature review].
AB  - Symptomatic involvement of the small bowel by metastasis from an extra-abdominal
      primary malignancy is rare, most commonly resulting from malignant melanoma and
      lung cancer; very rarely is small bowel involvement as first metastatic site. The
      Authors report a case of anaplastic thyroid carcinoma with lung metastasis, brain
      metastasis and an isolated metastasis to the small bowel leading intestinal
      obstruction due to small bowel intussusception. The Authors review the
      international literature about frequency, etiopathogenesis, clinical and
      diagnostic features and therapy of small bowel metastasis by extra-abdominal
      malignancies, especially by primary anaplastic thyroid carcinoma. Small bowel
      metastasis from extra-abdominal malignancies are very unusual, especially from
      anaplastic thyroid carcinoma, and the etiopathogenesis is still unknown. Clinical
      findings are typical for abdominal urgency, especially by small bowel obstruction
      from anaplastic thyroid carcinoma. Computed Tomography has an important role in
      detecting the type of intestinal obstruction despite it is often unable to
      diagnose an isolated metastasis. Best therapy is surgical resection, that allows
      the assessment of metastasis and the definitive staging. The prognosis is poor,
      despite long-term survival has been occasionally reported for isolated small
      bowel metastasis

PMID- 16910364
TI  - [Skin neuroendocrine carcinoma metastasis: a case report].
AB  - BACKGROUND: Merkel cell carcinoma (MCC) is a rare and aggressive skin tumour with
      a highly malignant nature whose appropriate treatment is still debated. The
      Authors report a case of cutaneous metastasis from neuroendocrine carcinoma and
      analyse new diagnostic and therapeutic options of neoplasms that occurs in sun
      exposed areas. METHODS: The authors present the clinical, immunocytochemical
      characteristic of primary and secondary skin localization of a neuroendocrine
      tumor that affected a woman. RESULTS: Histological and immunocytochemical
      analysis demonstrated that the secondary cutaneous localization appeared to be
      compared to the primary tumour. CONCLUSIONS: The case confirm the high incidence
      of regional metastasis; a wide surgical excision of tumor and regional
      lymphadenectomy is therefore recommended for primary treatment of MCC; the
      radiation treatment minimized the local recidives with long time survival.

PMID- 16910365
TI  - Presacral epidermoid cyst. A case report.
AB  - INTRODUCTION: Most of the primitive cystic neoplasms arising in the retrorectal
      presacral space are congenital. Presacral epidermoid cysts are classified as a
      type of developmental cysts, resulting from an error during the embryogenesis.
      They have a slowly-progressive growth that only lately can cause clinically
      remarkable symptoms. Most patients are middle-aged women. They are often
      asymptomatic. The discovery is almost always casual. It happens during controls
      like US, CT MRI, gynecological visit. The surgical treatment must be effected for
      a correct diagnosis of nature of the lesion and to remove the mass. In fact,
      infective complications may occur and the increasing volume of the cyst can give
      clinical symptoms. Posterior approach is indicated for low or mid presacral space
      tumors; it is the most commonly followed route. The abdominal approach may be
      adequate for large developmental cysts. CASE REPORT: A case of an incidentally
      found large presacral epidermoid cyst in a young woman, which was excised through
      an abdominal approach is reported.

PMID- 16910366
TI  - [Chronicle of an academic adventure].

PMID- 16910367
TI  - Preparing our healthcare system for large-scale disasters.

PMID- 16910368
TI  - Computerized neuropsychological examination of impulsiveness: A selective review.
AB  - There is a rapidly accumulating body of knowledge related to the neurobiology of
      impulsiveness from multidisciplinary neuropsychological and neuroimaging studies.
      This paper reviews recent research on impulsiveness in the context of
      neuropsychological theory and research. It has been emphasized that the
      controversy regarding the results of neuropsychological studies is related to
      different aspects of impulsiveness. The term "impulsivity" is related to more
      than one anatomical network among several brain regions. Impaired inhibition
      control, which has cognitive and behavioral dimensions, has a heterogeneous
      nature. Analysis of performance suggests that impulsivity includes three
      cognitive mechanisms: "prepotent inhibition," "interruptive inhibition" and
      "interference control,' each having separate neurological bases. Based on
      neuropsychological data it has been stated that both the orbitofrontal cortex,
      dorsolateral prefrontal cortex and anterior cingulate cortex are functionally
      disturbed among impulsive individuals. Bringing together knowledge from clinical
      experience, neuroimaging examination and neuropsychological assessment will lead
      to better and wider understanding of behavioral symptoms in clinical psychiatric
      practice.

PMID- 16910369
TI  - Understanding and treating kleptomania: new models and new treatments.
AB  - Kleptomania, characterized by repetitive, uncontrollable stealing of items not
      needed for personal use, is a disabling disorder that often goes unrecognized in
      clinical practice. Although originally conceptualized as an obsessive compulsive
      spectrum disorder, emerging evidence (clinical characteristics, familial
      transmission, and treatment response) suggests that kleptomania may have
      important similarities to both addictive and mood disorders. In particular,
      kleptomania frequently co-occurs with substance use disorders, and it is common
      for individuals with kleptomania to have first-degree relatives who suffer from a
      substance use disorder. Additionally, there is some suggestion that selective
      serotonin reuptake inhibitors, the treatment of choice for obsessive compulsive
      disorder, may lack efficacy for kleptomania. Instead, other medications (lithium,
      anti-epileptics, and opioid antagonists) have shown early promise in treating
      kleptomania. Evidence suggests that there may be subtypes of kleptomania that are
      more like OCD, whereas others have more similarities to addictive and mood
      disorders. Subtyping of individuals with kleptomania may be a useful way to
      better understand this behavior and decide on effective treatment interventions.

PMID- 16910370
TI  - Pathological gambling: comorbid psychiatric diagnoses in patients and their
      families.
AB  - OBJECTIVES: Pathological gambling is a highly prevalent and disabling impulse
      control disorder. Recent studies have consistently demonstrated that pathological
      gamblers respond well to treatment with selective serotonin reuptake inhibitors,
      mood stabilizers and opioid antagonists. These findings have supported the
      observation that pathological gambling is associated with anxiety and mood
      spectrum disorders as well as addictive disorders. METHODS: Fifty-two male
      pathological gamblers and their first-degree relatives (n=93) completed a semi
      structured DSM-IV-based diagnostic interview as well as a series of data
      collection instruments including the South Oaks Gambling Scale, the Hamilton
      Rating Scale for Depression, the Hamilton Rating Scale for Anxiety, the Yale
      Brown Obsessive-Compulsive Scale, and the Young Mania Rating Scale. The study
      subjects and their first-degree relative were compared to demographically matched
      normal controls (n=96). RESULTS: We found higher prevalence of alcohol, substance
      abuse, problematic gambling, depression, and anxiety disorders in the
      pathological gamblers and their first-degree relatives than in the control group.
      In particular, the scores on the Hamilton Rating Scale for Depression, the
      Hamilton Rating Scale for Anxiety, and the Yale-Brown Obsessive-Compulsive Scale
      were higher in the study group than in the control group. CONCLUSIONS: Our
      finding of a high prevalence of psychiatric comorbidity in pathological gamblers
      and their families raises the question of the proper classification of
      pathological gambling in the DSM-IV. Furthermore, the pattern of psychiatric
      disorders seen in the first-degree relatives can lead to new insights about the
      etiopathology of pathological gambling.

PMID- 16910371
TI  - Genetic correlates in trichotillomania--A case-control association study in the
      South African Caucasian population.
AB  - BACKGROUND: Trichotillomania (TTM), a prevalent and disabling psychiatric
      disorder characterized by repetitive hair-pulling, is presently classified as an
      impulse control disorder (ICD). Some have argued, however, that TTM is an
      obsessive-compulsive spectrum disorder (OCSD). There is some evidence that both
      disorders (OCD and TTM) are mediated by serotonergic (5-HT) and dopaminergic
      pathways. METHODS: The aim of the present investigation was to assess the role of
      candidate genes encoding components within the 5-HT and dopaminergic
      neurotransmitter pathways in mediating TTM. South African Caucasian TTM subjects
      (n=39), OCD (n=250) and control subjects (n=152) were genotyped for variants in 5
      HT and dopaminergic candidate genes. RESULTS: Both genotypic and allelic
      distributions of the 5-HT receptor 2A (5-HT2A) T102C variant were found to be
      significantly different between the TTM and control subjects (p=0.028 and
      p=0.024, respectively), and a trend towards significance was noted between the
      TTM and OCD subjects (p=0.084 and p=0.080 for genotype and allele analyses,
      respectively), with the T102T-genotype found to confer susceptibility to the
      development of TTM. CONCLUSION: This investigation provides preliminary evidence
      for the involvement of 5-HT2A in the molecular aetiology of TTM and supports the
      need for further replication in a larger dataset. The present data are consistent
      with previous findings that 5-HT2A plays a role in mediating impulse dyscontrol.

PMID- 16910372
TI  - Stalking.
AB  - Stalking is a frequently reported crime. It has a strong impact on the lives and
      mental health of the victims. It is perpetrated by persons who often suffer from
      mental disorders. This paper is an overview on the subject. It encompasses the
      various definitions of stalking, a number of classifications or sub-divisions of
      the phenomenon according to different approaches, a description of the
      psychopathology of the stalker, the psychological effect of the stalking on the
      victim, ways of evaluating and managing the phenomenon both in the victims and in
      the perpetrators, prevention of stalking, and also relevant bibliography. In
      addition, the paper includes an Appendix containing case series (clinical
      vignettes which include diagnosis, medical and legal interventions and outcome).

PMID- 16910373
TI  - Simple real-time computerized tasks for detection of malingering among murderers
      with schizophrenia.
AB  - It is our contention that computer-based two-alternative forced choice techniques
      can be useful tools for the detection of patients with schizophrenia who feign
      acute psychotic symptoms and cognitive impairment as opposed to patients with
      schizophrenia with a true active psychosis. In our experiment, Visual Simple and
      Choice Reaction Time tasks were used. Reaction time in milliseconds was recorded
      and accuracy rate was obtained for all subjects' responses. Both types of task
      were administered to 27 patients with schizophrenia suspected of having committed
      murder. Patients with schizophrenia who were clinically assessed as malingerers
      achieved significantly fewer correct results, were significantly slower and less
      consistent in their reaction time. Congruence of performance between the Simple
      and Choice tasks was an additional parameter for the accurate diagnosis of
      malingering. The four parameters of both tests (accuracy of response, reaction
      time, standard deviation of reaction time and task congruency) are simple and
      constitute a user-friendly means for the detection of malingering in forensic
      practice. Another advantage of this procedure is that the software automatically
      measures and evaluates all the parameters.

PMID- 16910374
TI  - Therapist-patient sexual relations: results of a national survey in Israel.
AB  - BACKGROUND: Studies focusing on Patient-Therapist sexual relations have been
      carried out mainly in the U.S. This study comes to broadly explore this
      phenomenon in Israel. METHOD: An indirect questionnaire was sent to all 1,817
      psychiatrists, psychologists and social workers who are members of the Israeli
      Psychiatric Association, Psychologists Association and Psychotherapy Association,
      respectively. RESULTS: 29% of the responding therapists reported that at least
      one of their patients had experienced sexual relations with the most recent,
      former therapist. LIMITATION: The design of our survey made it impossible for us
      to conduct a follow-up after termination of therapy and to differentiate
      intercourse from nonintercourse sexual exploitation. CONCLUSIONS: Similar numbers
      of the gender of the exploiting therapist and exploited patients were obtained
      for both the indirect current Israeli study and previous U.S. studies. This may
      suggest that such parameters are influenced by common norms regarding the
      relationships between men and women of both societies, and from the
      psychotherapeutic dyadic situation.

PMID- 16910375
TI  - Does psychiatric comorbidity affect drug abuse treatment outcome? A prospective
      assessment of drug abuse, treatment tenure and infectious diseases in an Israeli
      methadone maintenance clinic.
AB  - OBJECTIVE: The influence of psychiatric comorbidity in drug addicts on
      therapeutic outcome is an important unresolved issue. We studied the links
      between patterns of psychiatric comorbidity and psychological distress with
      treatment outcome variables. METHOD: 151 methadone maintenance patients underwent
      a structured clinical interview, twice-weekly urinalysis for traces of drugs of
      abuse, and completed psychological distress and risk-taking questionnaires for
      periods of up to three years. Treatment tenure, demographics and hepatitis C
      status were recorded. RESULTS: High levels of lifetime (82.8%) and current
      (66.2%) Axis I psychiatric comorbidity were mostly anxiety and affective
      disorders many of which were substance induced. Patients with current psychiatric
      comorbidity had significantly more current substance use disorders, although they
      did not abuse more drugs or remain in treatment less time than patients with no
      current psychiatric comorbidity. Patients with a lifetime Axis 1 disorder
      remained in treatment longer. Severity of psychological distress was related to
      current substance-related diagnoses, benzodiazepine abuse, higher methadone
      dosage, risk-taking behavior and the presence of hepatitis C. CONCLUSIONS:
      Severity of psychological distress, but not comorbid psychiatric disorders, has a
      major negative association with treatment outcome of patients receiving methadone
      maintenance treatment (MMT). Surprisingly patients with comorbid mental illness
      seem to remain in treatment longer than those without. Therapeutic efforts should
      also focus on treating subjective distress and its possible influence upon drug
      use behavior.

PMID- 16910376
TI  - Suicidal attempts admitted to a general hospital in the Western Galilee: an inter
      ethnic comparison study.
AB  - BACKGROUND: Deliberate self-harm is a relatively frequent cause of consultation
      in the emergency room of general hospitals. Despite its importance, few
      epidemiological studies of self-injury in Israel have been carried out, and of
      these, they mostly covered selected population groups. OBJECTIVES: To provide
      epidemiological data on self-harm in patients examined in the emergency room of a
      general hospital in the Western Galilee, with special emphasis on differential
      sociodemographic and clinical characteristics of the Arab and Jewish subjects.
      METHODS: Demographic, clinical, and self-harm characteristics were extracted from
      hospital files for people aged 18 years and older admitted to the general
      hospital in Nahariya, Western Galilee, over a 24-month period (January 1996 to
      December 1997) following a suicidal attempt. Chi-square statistics, two-tailed t
      tests, and logistic regression analyses were used to test the significance of
      inter-ethnic differences in risk factors. RESULTS: The overall incidence rate of
      suicidal attempts was 16.7 per 100,000 population of Northern District in 1996
      (Arabs, 24.4 and Jews, 11.0); or 37.6 per 10,000 admissions (Arabs, 44.2 and
      Jews, 30.3). Among the Jewish male subjects, attempts rose markedly after the age
      of 40, while among their Arab counterparts the age distribution was even
      throughout all age groups. Among Jewish females, admissions for self-harm rose
      gradually with age, while among the Arab women there was a peak at the 20-29 year
      age group. Both ethnic groups differed significantly in their sociodemographic
      and clinical profiles, but they shared common characteristics with regard to the
      attempt. CONCLUSIONS: Our findings suggest differential ethnic patterns of risk
      factors for self-harm. Further in-depth investigation of deliberate self-harm is
      warranted to better explore these factors.

PMID- 16910377
TI  - Variety in mental health research.

PMID- 16910378
TI  - Analysis of clinical characteristics and antipsychotic medication prescribing
      practices of first-episode schizophrenia in Israel: a naturalistic prospective
      study.
AB  - BACKGROUND: Investigation of the clinical presentation and treatment of first
      episode psychosis is important in order to exclude effects of age, chronic
      illness, long-term treatment and institutionalization. The aim of this
      descriptive study was to investigate the management practices of first-episode
      schizophrenia in a cohort of patients in Israel and to document use of the
      various "typical" or "atypical" antipsychotic agents. METHOD: Fifty-one
      consecutive patients (26 M, 25 F) with first-episode psychosis were recruited for
      study participation and were administered either typical or atypical
      antipsychotic medications in a naturalistic manner. RESULTS: While an
      approximately equal number of subjects received typical and atypical medications
      at illness onset, a prominent shift to atypical antipsychotic treatment occurred
      over the study course; 18 subjects had medication class shifts: 17 from typical
      to atypical, and one from atypical to typical. Negative symptoms did not affect
      length of hospitalization, but were associated with aggression. Higher depression
      rates were noted in patients with long hospitalizations who received typical
      antipsychotic medications. Immigrants were admitted at an age approximately four
      years older than native-born Israelis. CONCLUSIONS: The prominent shift from
      "typical" to "atypical" antipsychotic medications may indicate sensitivity of
      first-episode psychotic patients to side-effects of "typical" medications and
      prominence of use of atypical medications in this patient subpopulation be it due
      to improved efficacy over time or successful marketing. Unique cultural and
      population characteristics may contribute to the manifestation of first-episode
      psychosis and suggest the importance of more effective outreach to the immigrant
      population in order to manage an apparent treatment delay.

PMID- 16910379
TI  - The comorbidity of anxiety disorders in bipolar I patients: prevalence and
      clinical correlates.
AB  - The purpose of this study was to determine the prevalence of lifetime anxiety
      disorders in bipolar I patients in Sanliurfa, Turkey, and to assess the
      association between comorbidity and several demographic and clinical variables.
      Seventy bipolar I patients in remission were assessed by means of the Structured
      Clinical Interview for DSM-IV axis I Disorders-Clinician Version (SCID-I-CV),
      Anxiety Disorder Module in order to detect lifetime comorbid anxiety disorders.
      Nineteen (27.1%) bipolar I patients were diagnosed with at least one lifetime
      comorbid anxiety disorder. The most common anxiety disorders in this sample were
      obsessive compulsive disorder (12.8%) and specific phobia (12.8%), followed by
      panic disorder (5.7%). Anxiety disorder comorbidity appears to be associated with
      greater number of hospitalizations, psychotic symptoms and suicide attempts in
      patients with bipolar I disorder. As comorbidity has a clear impact on the course
      of bipolar patients, special attention to this issue should be paid when
      interviewing bipolar patients.

PMID- 16910381
TI  - Postpartum hospitalization of psychotic parents with their infant: a case study.
AB  - BACKGROUND: Parents with mental illness are at risk for exacerbations during the
      postpartum period. The management of family members needing concurrent
      psychiatric hospitalization is unclear. This article describes the advantages and
      difficulties of a family hospitalization, focusing on the splitting processes in
      the staff and the use of "couple ego functions'. DATA: A couple, simultaneously
      psychotic after the sequential births of two children, were hospitalized
      separately after the birth of the first child, and simultaneously in the same
      room after the birth of the second child. RESULTS: The hospitalization of the
      couple with their infant led to a shorter, less stressful hospitalization, and
      strengthened the functioning of the family unit. CONCLUSIONS: Simultaneous
      hospitalization of family members is feasible and may lead to better clinical
      results.

PMID- 16910380
TI  - Follow-up of preschool children with severe emotional and behavioral symptoms.
AB  - BACKGROUND: Biological and environmental factors have been related to the
      persistence of psychopathology in preschool children. The objective of the study
      was to identify the factors predicting the clinical outcome in preschool
      inpatients with emotional and behavioral disorders. METHOD: Twenty-eight children
      aged 3 to 6.5 years attending a therapeutic nursery were evaluated. Clinical data
      were collected from the children's charts, including: biological parameters,
      developmental milestones, intelligence level, socioeconomic status, and stressful
      life events. Severity of symptoms at follow-up was assessed using the Clinical
      Global Impression Scale. RESULTS: Low socioeconomic status, excess stressful life
      events, and female gender were associated with poor clinical outcome. Biological
      factors such as pregnancy and birth complications and genetic factors were not
      significant predictors. LIMITATIONS: The study was limited by its retrospective
      design and small sample size. CONCLUSIONS: More effort in social interventions
      and supportive family therapy may improve the outcome of young children with
      emotional and behavioral problems.

PMID- 16910382
TI  - Tattoo designs among drug abusers.
AB  - Forty-one males with drug abuse who had tattoos with designs related to drug use
      were selected from a larger sample of tattooed males in forensic psychiatric
      wards, prisons and military recruitment centers during the period 1986-2000 in
      the former Soviet Union. Two-thirds of the tattoo images were related to a
      specific drug, some served to hide signs of repeated drug use, others to identify
      ideal sites for injection. Knowledge of these details may be helpful to
      clinicians, although images may be influenced by current trends.

PMID- 16910383
TI  - Changes in stability of first-admission psychiatric diagnoses over 14 years,
      based on cross-sectional data at three time points.
AB  - BACKGROUND: Stability of diagnoses over time is an important criterion of
      reliability of any diagnostic system. AIMS: To compare the stability of diagnoses
      among hospitalized psychiatric patients over 14 years, based on cross-sectional
      data at three time points. METHOD: Diagnoses extracted from the National
      Psychiatric Case Register concerning psychiatric patients first admitted during
      1989 (n=2996) were compared to those who were admitted during 1996 (n=3021) and
      2003 (n=4041). Stability of diagnostic categories was measured by positive
      predictive value of admission diagnosis at discharge from hospital. RESULTS:
      There was no significant difference in diagnostic stability for most diagnostic
      categories between 1989 and 1996 patient cohorts. However, over the seven
      following years (cohort 2003) the diagnostic stability had been substantially
      increased: by 19% for affective disorders, by 18% for childhood disorders, by 17%
      for organic conditions, by 14% for neurotic disorders, by 12% for both
      schizophrenia and drug and alcohol dependence. CONCLUSIONS: In long-term
      perspective, reliability of most diagnostic categories of mental disorders has
      clearly improved.

PMID- 16910384
TI  - Antisocial personality disorder in Turkish substance dependent patients and its
      relationship with anxiety, depression and a history of childhood abuse.
AB  - The prevalence of antisocial personality disorder (ASPD) in treatment-seeking
      Turkish substance dependent patients and the relationship of ASPD with clinical
      characteristics were studied. Participants were 132 inpatients with substance
      dependence according to the Structured Clinical Interview for DSM-IV (SCID-I),
      Turkish version. The clinician applied a semi-structured socio-demographic form,
      SCID-I, SCID-II, Childhood Abuse and Neglect Questionnaire (CANQ), Michigan
      Alcoholism Screening Test (MAST), Beck Depression Inventory (BDI), and Beck
      Anxiety Inventory (BAI). Among the 132 substance dependent patients, 31 (23.5%)
      had ASPD diagnosis and 56 (42.4%) had no personality disorder or personality
      traits. Rate of childhood physical abuse, childhood verbal abuse, childhood
      neglect, suicide attempt history, self-destructive behavior and lifetime major
      depression were higher among patients with ASPD. Also mean scores of BDI, BAI and
      MAST were higher among patients with ASPD. The high rate of ASPD found among
      Turkish substance dependent patients suggests that special attention must be paid
      to identify ASPD in this group. Findings in this study showed that there is an
      association between ASPD and childhood abuse, lifetime major depression and
      severity of substance use.

PMID- 16910385
TI  - "Internet delusions": the impact of technological developments on the content of
      psychiatric symptoms.
AB  - The inclusion of computers and the Internet in our daily lives has become an
      increasingly pervasive phenomenon. Naturally, this phenomenon found its
      reflection in the quick inclusion of these technologies in the content of
      delusions. There have already been a few reports describing patients with
      Internet delusions. In this report, we describe two patients and their social
      background who were without previous psychiatric history and whose first
      psychosis involved delusions surrounding the Internet. Our opinion is that
      Internet delusions do not represent a new diagnostic entity, but rather modified
      delusions of persecution, broadcasting and control.

PMID- 16910386
TI  - Acute intermittent porphyria: psychosis as the only clinical manifestation.
AB  - Acute intermittent porphyria (AIP) is the most common of the four forms of
      neuroporphyria. AIP mimics a variety of disorders and thus poses a diagnostic
      quagmire. Abdominal pain occurs in 90-95% of the attacks. Some patients develop
      psychiatric symptoms such as psychosis similar to schizophrenia. The diagnostic
      difficulty may lead to under-diagnosis of patients who present with strictly
      psychiatric symptoms. This assumption is supported by a high prevalence of AIP in
      psychiatric hospitals. Therefore, we encourage a high index of suspicion for AIP
      in psychiatric patients in order to prevent false psychiatric diagnosis. In
      addition we discuss psychotropic drugs that may exacerbate acute attacks in
      undiagnosed patients. We report a case in which the diagnosis of AIP was clouded
      by the presence of only psychiatric symptoms. The clue for diagnosis was an
      anamnestic detail of the use of a porphyrogenic drug prior to the admission. The
      diagnosis of AIP was supported by excess of alpha aminolevulinic acid (ALA) and
      porphobilinogen (PBG) in urine concomitantly with a decrease in porphobilinogen
      deaminase (PBGD) activity in erythrocytes. The diagnosis was further strengthened
      by the fact that the patient's father was identified as an AIP carrier. However,
      in the absence of typical organic symptoms of porphyria, one cannot definitely
      rule out the presence of schizophrenia in this patient in addition to AIR

PMID- 16910387
TI  - Rehospitalizations among psychiatric patients whose first admission was
      involuntary: a 10-year follow-up.
AB  - OBJECTIVES: To examine the characteristics of patients whose first admission to
      Israel's psychiatric units was involuntary, and to identify a specific profile of
      the patients at increased risk for future readmissions. Our hypothesis was that
      when the first admission of a patient was involuntary, the number and duration of
      future hospitalizations would be greater. METHOD: We used information extracted
      from the National Psychiatric Case Registry on all patients admitted for the
      first time during 1991 (N=2150) and on their follow-up over the next ten years.
      Chi-square statistics were used to test for significance differences in
      demographic and clinic variables between patients hospitalized voluntarily and
      those hospitalized involuntarily. Multiple regression analysis was performed to
      identify a specific profile of risk of recidivism during a ten-year period (1991
      2000). RESULTS: Compared with patients admitted voluntarily, those who were
      admitted involuntarily had a significantly greater number and duration of
      rehospitalizations. They were more likely be diagnosed as suffering from
      schizophrenia while the voluntarily admitted patients were more likely be
      diagnosed as having an affective disorder. Risk factors for the number of
      readmissions included: young age, legal status (involuntary) of the first
      admission, as well as period of residence in the country. Risk factors affecting
      the duration of readmissions were single/widowed status, native born and a
      suicide attempt in the two months prior to the first admission. CONCLUSIONS: Two
      distinct profiles for the number ofreadmissions and inpatient days were
      identified. A diagnosis of schizophrenia and selected demographic variables were
      better at predicting risk of recidivism than the involuntary legal status of the
      first admission.

PMID- 16910388
TI  - [Adenoid cystic carcinoma of the larynx-hypopharynx. A case report and review of
      the literature].
AB  - Laryngeal or hypopharyngeal localization of adenoid cystic carcinoma is rare due
      to the poor distribution of the accesory salivary glands in this area. We report
      one case of such neoplasm on that area, with its diagnosis confirmed
      histologically. The required a total laryngectomy with later reoperations because
      of hemorrhage and pharyngeal fistula. One year after the surgery and in spite of
      postoperative radiotherapy multiple pulmonary metastasis were detected causing
      the death of the patient. We review the literature of this tumor whose prognosis
      is much worse than epidermoid or scamous carcinoma.

PMID- 16910389
TI  - [Diffuse sclerosing papillary carcinoma mimicking chronic lymphocytic
      thyroiditis. A unusual neoplasm variant].
AB  - We report the clinical case of a 39 years old female diagnosed as a chronic
      lymphocytic tiroiditis by F.N.A.B. with multinodular goiter of long evolution.
      The patient was operated by total thyroidectomy and her final anatomopathologic
      result was papillary carcinoma diffuse sclerosing variant. During the surgical
      act several cervical nodes were detected and removed being informed the most of
      them as metastasic. A review of the literature at respect of this malignant
      neoplasm is performed.

PMID- 16910390
TI  - [Rhabdomyosarcoma of soft palate. A case on purpose].
AB  - The rabdomiosarcoma (RMS) are infrequent tumors. They are principally described
      in infancy and located in 35% of the cases in head and neck. The nasopharynx
      localisation is relatively rare, being in these cases the tongue, palate and oral
      mucosa the preferent places of establishment. Classically the patient presented
      very low standard healing with surgery and radiotherapy. The introduction in the
      middle 70 of systematic chimiotherapy as complementary treatment, improved the
      survival rate in large scale. In this article the case of an adolescent patient,
      who presented a RMS at the level of the soft palate, the diagnostic procedure and
      the therapeutic decision adopted, after revision of the last studies at this
      respect, are described.

PMID- 16910391
TI  - [Parotid phlegmon with involvement of both lobes. Report of a case].
AB  - The pathologic processes involving the parotid gland include a vast group of
      lesions, acute and chronic inflammations, benign and malign tumors, traumas or
      degenerative processes. We report the case of a 55 years old male diagnosed as
      left parotid phlegmon with involvement of both lobes, especially the deep one,
      who required admission and endovenous medical treatment for 6 days up to the
      resolution of the symptoms.

PMID- 16910392
TI  - [Atypical thyrogloss cyst].
AB  - The thyrogloss cysts present themselves usually as unique tumorations in the
      anterior cervical zone, more frequently in the second decade of life and
      affecting equally the two sexs. They move typically with the movements of
      deglution and can increase its volume with infections processes. In seldom
      occasions, the thyrogloss cysts can present symptoms as dysphonia, dysphagia or
      dyspnea facts that can suggest its laryngeal extension. METHODS: We present a
      case of a patient affected by dysphonia of long evolution, associated to the
      presence of a cervical mass. The CT showed a cervical cyst with extension to the
      left preepiglottic and paraglottic space with compression of the left thyroid
      wing. Although the clinic impression was a laryngeal neoplasia, the CT helped to
      realize the diagnosis ofthyrogloss cyst. During the surgery the thyrogloss cyst
      was removed with success, with the technique of Sistrunk and the patient
      recovered the voice. CONCLUSIONS: We present this case and realize a
      bibliographic revision on thyrogloss cysts, with atypical symptoms. We discuss
      also the role of CT in the diagnostic process in these types of processes.

PMID- 16910393
TI  - [Palatine tonsil lipoma].
AB  - Lipomatous tumors represent an unfrequent cause for upper aerodigestive tract
      neoplasms, specially concerning the palatine tonsils, that should be included in
      their differential diagnosis. A case of palatine tonsil lipoma in a 11 year-old
      girl is reported and a revision of the available literature and some
      considerations about this condition are provided.

PMID- 16910394
TI  - [Epiglottic cysts: an unsuspected cause of dysphagia. Anatomo-clinical study and
      treatment options].
AB  - Laryngeal cysts represent a defined group of benign lesions with an actual not
      well know pathogenesis although fibrosis and glandular obstruction or congenital
      origin are presumed rather than new growths. When such cysts occur, as a general
      rule, with the exception of some particular locations, they develop with very few
      symptoms until very large size is reached or a fast growth is produced due to
      bleeding or infection. Under these conditions, these cysts may represent a
      potential treatening lesion and so surgery is recommended under any circunstance
      and anaesthetic procedure should be case-addapted. A case of an impressive large
      epiglottic cyst is presented and a revision and discusion on the controversies
      and available literature are provided.

PMID- 16910396
TI  - [Peritonsillar infection. Out-patient management].
AB  - INTRODUCTION: Peritonsillar infections are the most frequent deep infections in
      head and neck. The estimated annual incidence is 30 cases per 100.000
      inhabitants. PATIENTS AND METHODS: A retrospective study was undertaken in 132
      patients with peritonsillar infection. A diagnostic and therapeutic protocol was
      used consisting on diagnostic needle aspiration, incision and drainage and
      intravenous antibiotic and steroids. RESULTS: 35,6% were peritonsillar phlegmons
      and 64,4% were abscesses. The median of hospital monitoring was 9,2 hours. Only
      25,8% were admitted to the hospital. Six patients had recurrences of the symptoms
      during the study. DISCUSSION: The needle aspiration is useful in differential
      diagnosis between phlegmons and abscesses. Bacteriologic studies are not
      necessary in the routine management of peritonsillitis. Surgical treatment of
      these patients is controversial. Incision and drainage seems to be appropiated in
      the management of this pathology. Admission to the hospital is not always
      necessary if a correct outpatient control is possible.

PMID- 16910395
TI  - [Retropharingeal abscess in paediatrics].
AB  - Retropharingeal abscess is a potentially lethal but infrequent infection of the
      retropharyngeal space, thanks to the use of antibiotics. Caused by a suppurative
      lymphadenitis secondary to a locoregional infection of the head and neck, it is
      the most frequent abscess in Paediatric age. It must be present in our
      differential diagnosis when facing a torpid development of head and neck
      infectious processes accompanied by adenitis. A cervical lateral X-Ray should be
      done without delay and in case of doubt, a CAT--scan is mandatory. We protocolise
      its diagnosis and treatment in order to avoid its serious complications.

PMID- 16910397
TI  - [Parotid gland myoepitheliomas. Differential diagnosis with pleomorphic adenoma].
AB  - Myoepitheliomas are rare benign tumours of head and neck. The parotid gland is
      the most common site of origin. It consists on proliferation of myoepithelial
      cells and it shows some features similar to preomorphic adenoma although the
      ductal elements are very low. Diagnosis requires histology and
      immunohistochemistry because fine needle aspiration often shows erroneous
      results. Limited parotidectomy is the choice treatment. We report two cases of
      parotid gland myoepithelioma confirmed by immunohistochemistry.

PMID- 16910398
TI  - [Hemilingual abscess].
AB  - Lingual abscess is an extremely rare entity since the discovery of antibiotics,
      which, despite of its seriousness, it is usually a cause of death. We describe
      the case of a right hemilingual abscess, diagnosed by MRI scan because of its
      poor symptoms. This case is unique because of it affects the hemilingual central
      part and free edge. We discuss the most relevant aspects of this pathology.

PMID- 16910399
TI  - [Why treatment of insomnia is so important--sleeping for good health].

PMID- 16910400
TI  - [Exanthema after antibiotic therapy--not always is it an allergy].

PMID- 16910401
TI  - [100 years ago in the MMW: the birth of allergy. An overview from the beginnings
      to molecular therapy].

PMID- 16910402
TI  - [Clemens Freiherr von Pirquet, developer of the concept of allergy].
AB  - The pediatrician and scientist, Clemens Freiherr von Pirquet (1874-1929) was the
      first to coin the term "allergy". His experiments with Behring's serum, which he
      administered to sick children, led him to an awareness of an interaction between
      the human organism and pathogens. In his article published in the Muncher
      Medizinischen Wochenschrift in 1906, he laid the foundation stone for modern
      allergology.

PMID- 16910403
TI  - [Allergy--triggers of life-threatening and fatal anaphylaxis].
AB  - Cases of life-threatening and fatal anaphylaxis represent the most extreme forms
      of acute allergic reactions. They are estimated to have an incidence of 1-3 per
      10,000 persons, with an associated death rate of 0.5-2%. Medicinal drugs, insect
      stings and foods are the most common triggering agents. In particular in the case
      of drugs, the median time lapse between contact with the triggering agent and
      death is a very short 5-10 minutes. Fatal anaphylaxis due to foods usually leads
      first to dyspnea and then to respiratory failure. Allergic bronchial asthma
      represents a major risk factor. Knowledge of the allergens capable of triggering
      life-threatening and fatal anaphylaxis makes it easier for the physician to
      assess the risk potential when confronted by an emergency situation.

PMID- 16910404
TI  - [Environmental factors as determinants of allergy development].
AB  - Environmental factors may be either the cause of, or have a modulating effect on,
      the development of an allergy. The influence of the causal factor "exposure to an
      allergen" has in the past been underestimated--and this applies in particular to
      pollinosis. The increase in the prevalence of allergies observed over the last
      decades can possibly be explained not merely by an increase in the allergen
      burden, but also by a lack of protective factors. Further research is needed to
      clarify the situation.

PMID- 16910405
TI  - [Emergency checklist: reactions to insect venom].

PMID- 16910406
TI  - [Effect of a homeopathic arnica preparation (D4) on delayed onset muscle
      soreness. Placebo-controlled crossover study].

PMID- 16910407
TI  - [Diverticulitis and diverticulosis].
AB  - Over the last 100 years, the prevalence and incidence of diverticulosis and
      diverticular disease have increased dramatically in western industrialized
      countries. The main reasons for this are considered to be changes in eating
      habits, and the increasing age of the population. Conservative treatment of
      diverticulitis is an initial period of fasting and antibiotic treatment. For
      recurrence prevention, a fiber-rich diet is recommended. Studies providing
      evidence in support of the general recommendation of recurrence prophylaxis with
      poorly absorbed antibiotics, mesalazine or probiotics are to date not adequate.
      Elective prophylactic sigmoid resection is to be recommended following an episode
      of diverticulitis with complications, and after an episode of uncomplicated
      diverticulitis in long-term immunosuppressed patients who have already had an
      attack. Elective sigmoid resection after a healed second attack of uncomplicated
      diverticulitis is controversial.

PMID- 16910408
TI  - [Physician reimbursement: euros instead of points, but mostly just flat rates].

PMID- 16910409
TI  - [Established physicians at greater disadvantage than employees].

PMID- 16910410
TI  - [Lowering blood pressure substantially--and the diabetes risk as well?].

PMID- 16910412
TI  - [Dual life as physician and poet].

PMID- 16910411
TI  - [Effectiveness duration determines selection].

PMID- 16910413
TI  - [Lower limb amputations caused by tumours and prosthetic rehabilitation in
      Croatia from 2000 to 2004].
AB  - During the period of five years (2000-2004) we monitored 46 patients (25 males
      and 21 females) who were admitted to Clinical Institute for Rehabilitation and
      Orthopaedic Aids in Zagreb for the first prosthetic rehabilitation following the
      lower limb amputation which was caused by a tumour. The average age of patients
      was 51 +/- 17.11 years. According to the pathohistological diagnosis the most
      common cause of lower limb amputations was osteosarcoma. According to the level
      of amputation the most frequent was trans-femoral amputation (50%) and the least
      frequent was knee disarticulation (8.7%). The average number of days from the
      amputation to the beginning of prosthetic rehabilitation was 108 +/- 67.05. At
      the time of admission 15.2% of patients had local complications of the stump and
      34.8% of patients complained of phantom pain. The average number of days of
      prosthetic rehabilitation was 35 +/- 7.94. The medium daily use of the prosthesis
      was 5 hours and the medium walking speed was 12 sec/10 m. At the time of
      admission for the prosthetic rehabilitation 10.9% of patients used a wheelchair,
      8.7% walked with a walker and others with two crutches. At the time of discharge
      89.1% of patients were able to walk with a prosthesis and two crutches, 4.4% with
      one crutch and 6.5% were able to walk without crutches. We can be satisfied with
      the results of prosthetic rehabilitation because patients regained mobility and
      full independence in performing their daily activities.

PMID- 16910414
TI  - [The carpal tunnel syndrome: medical and economic advantages of well-timed
      surgical treatment].
AB  - Carpal tunnel syndrome (CTS) is a somewhat neglected medical and economic
      problem, and surgery is one of the therapeutic options. We analyze the outcomes
      of surgical treatment in 114 consecutive patients (154 hands). Before the
      surgery, physical therapy was implemented (96% cases) and the patients were
      frequently on a sick leave (42% cases). Immediately before the surgery, the
      patients suffered intensive pain (median 7 on a 0-10 scale), and had a reduced
      hand function (median 2 on a 0-10 scale). After the surgery (6-12 months), the
      pain was reduced (difference -5.0, 95% CL -5.5, -4.5, p<0.001), and the function
      improved (difference 4.5, 95% CLs 4.0, 5.0, p<0.001). Longer time interval
      between referral to a primary care physician and referral to an orthopeadic
      surgeon (>1 year in 48% of the cases) was an independent negative predictor for
      these outcomes. Total difference in costs for sick leaves and physical therapies
      between the pre- and postoperative periods was estimated at approximately
      269.030,00 to over 375.315,00 euros. The time between the entrance into the
      healthcare system and recognition of the need for surgical treatment of CTS needs
      to be reduced in order to get better medical and economic results.

PMID- 16910415
TI  - [Reconstruction of traumatic defect of the upper third of the ear].
AB  - Replacement of defect of the upper third of the ear consequent to a traffic
      accident was successfully performed using modified Antia-Buch technique. Creation
      of wider and longer skin-cartilage flaps and their increased rotation allowed
      formation of the upper edge of the ear without tension and postoperative
      complications. Although the repaired ear is a bit smaller to attain adequate
      relief and matching color, the use of this method achieved a satisfactory
      esthetic result.

PMID- 16910416
TI  - [Doppler echocardiographic assessment of diastolic function of left ventricle].
AB  - Approximately half of the patients with overt congestive heart failure (CHF) have
      diastolic dysfunction without reduced ejection fraction (LVEF>50%). Diastolic
      dysfunction is an abnormality in left ventricular myocardial relaxation and/or
      compliance that alters the ease with which blood is accepted into the left
      ventricle during diastole. Elevated pressures in the left atrium are
      compensatory, ensuring adequate filling. All patients with systolic dysfunction
      have concomitant diastolic dysfunction. Indeed, in patients with CHF and reduced
      systolic function the level of diastolic dysfunction influences the severity of
      symptoms. It is now clear that hypertension, coronary artery disease and other
      diseases and conditions commonly produce diastolic dysfunction in the absence of
      significant systolic dysfunction. Accurate noninvasive Doppler-echocardiographic
      assessment of the presence and severity of diastolic impairment is crucial to the
      broad application and understanding of this common condition. This review
      discusses the clinical impact of classic and recent echocardiographic
      contributions to the field of diastology.

PMID- 16910418
TI  - [C-reactive protein in cardiovascular risk evaluation].
AB  - Inflammation plays a central role in the initiation, progression and
      destabilization of atheroma. In an attempt to improve global cardiovascular risk
      assessment considerable research has focused on inflammatory markers,
      particularly high sensitive C-reactive protein (hs-CRP). It has been reported
      that hs-CRP levels more than 3 mg/L identify increased risk of initial
      cardiovascular events in healthy individuals and also increased risk of adverse
      events in patients with stable and unstable angina, acute myocardial infarction,
      and in patients undergoing coronary revascularization procedures. Furthermore,
      several pharmacologic (eg. aspirin, statins, tienopiridins) and lifestyle
      interventions (eg. weight loss, smoking cessation, regular exercise) known to
      reduce cardiovascular events rates have also been shown to lower levels of hs
      CRP. Therefore, hs-CRP levels may also prove useful in targeting therapy for
      primary and secondary prevention. This review discusses the role of hs-CRP in the
      pathogenesis of atherosclerosis and its application in every day clinical
      practice, including the role of hs-CRP in identification of high-risk
      individuals, monitoring of the coronary artery disease activity, and assessment
      of therapeutic effect on the inflamatory component of the cardiovascular process.

PMID- 16910417
TI  - [Imatinib in gastrointestinal stromal tumor treatment--results from University
      Hospital Centre Zagreb].
AB  - Gastrointestinal stromal tumours (GIST) may be defined as intraabdominal
      mesenchymal tumours that express KIT protein or have an activating mutation in
      class III receptor tyrosine kinase gene (KIT or PDGFRalpha). Most GISTs respond
      to imatinib mesylate, which selectively inhibits both KIT and PDGFRalpha, and is
      now considered standard systemic therapy for advanced GIST. We assessed the
      antitumour response of patients treated with imatinib mesylate who had advanced
      and/or metastatic (GIST). In the Department of Medical Oncology fourteen (14)
      patients with advanced GIST were treated in the period from year 2002 to 2004.
      Imatinib mesylate was applied at the dose of 400 mg daily. Only two patients
      required dose enlargement up to 800 mg. All tumours had positive
      immunohystochemical expression of KIT. Median age of patients was 56 years. 12
      male patients and 2 female patient was treated. Considering primary site of
      tumour we had 6 small intestine, 4 mesenterium and 4 gastric tumours. Mean
      duration of the treatment was 14 months (5 to 30 months). Six patients had
      partial remission, six had stable disease and two progression. Complete remission
      has not been achieved in any patient. Side-effects were mild and no patient
      required dose reduction or treatment discontinuation. Our results show the
      effectivness of targeted antitumour therapy with imatinib mesylate in advanced
      and/or metastatic GIST, and correspond to those in literature.

PMID- 16910419
TI  - [The estimation of glomerular filtration rate using prediction equations].
AB  - In clinical practice, serum creatinine is most commonly used to estimate
      glomerular filtration rate (GF) although it is well known that serum creatinine
      may be influenced by GF and factors independent of GF (age, sex, race, body size,
      diet, certain drugs and analytical methods). Creatinine clearance is a more
      sensitive marker of GF, but it overestimates GF because of tubular secretion of
      creatinine, and it often involves errors in 24-hour urine collection. According
      to the NKF/KDOQI (National Kidney Foundation Kidney Disease Outcome Quality
      Initiative) guidelines, the level of GF should be estimated from prediction
      equations taking into accout serum creatinine concentration and demographic
      characteristics. The aim of this work is to emphasize the clinical usefulness of
      these equations in estimating GF. Using prediction equations to estimate GF does
      not require timed urine collection susceptible to errors which are the most
      common underlying cause of unreliable estimation of GF done by creatinine
      clearance.

PMID- 16910420
TI  - [Strontium ranelate--new paradigm in the treatment of postmenopausal
      osteoporosis].
AB  - Osteoporosis has become a global public health issue due to the fact that the
      world population has gotten older. In the past ten years we have witnessed a
      great improvement in the treatment of postmenopausal osteoporosis. The anti
      resorptive drugs are the most presribed ones. In the last couple of years
      osteoanabolic drug, a teriparatid, was introduced into the clinical use, and
      recently a strontium ranelate has occured as a drug with osteoanabolic and
      antiresorptive effect in bone formation. Clinical trials (phase III) have proved
      the efficiency of strontium ranelate in postmenopausal osteoporosis treatment.
      Strontium ranelate is a drug characterized by the new paradigm of action
      mechanism on bone, which has its place among the already well-proven drugs in
      postmenopausal osteoporosis treatment.

PMID- 16910421
TI  - [Harmonization of laboratory medicine in Croatia].
AB  - In order to harmonize laboratory results in the field of general medical
      biochemistry at the national level, analytical methods and analytical quality
      goals based on biological criteria together with common reference intervals were
      recommended. The following parameters are included: general biochemical
      parameters (metabolites and substrates, enzymes, electrolytes, microelements,
      proteins, lipids), routine urine and stool analysis and laboratory haematology
      and coagulation. The main purpose of external quality control in medical
      biochemical laboratories is to ensure independent and objective evaluation of
      laboratory test results in order to promote harmonization and achieve a high
      degree of interlaboratory comparability. The recommended reference intervals were
      produced on a representative sample group of urban population in Croatia for
      school children, adolescents and adults. For pediatric population, reference
      intervals were recommended according to the literature data. The recommended
      laboratory methods and corresponding reference intervals in the field of general
      medical biochemistry have to be used in all medical biochemical laboratories in
      Croatia since January 1, 2005.

PMID- 16910422
TI  - [PubMed recognizes Croatian!].

PMID- 16910423
TI  - [Laparoscopic colorectal surgery].

PMID- 16910424
TI  - [Surgical treatment of primary lymphedema of penis and scrotum].

PMID- 16910425
TI  - Fascinating rhythm: atrial fibrillation-the beat goes on.

PMID- 16910426
TI  - Stem cell research: the debate continues.

PMID- 16910427
TI  - Why we will never get an increase in our Medicare fee schedules.

PMID- 16910428
TI  - The future of electronic medical records--part II.

PMID- 16910429
TI  - EMR implementation spells increased efficiency & satisfaction to docs & patients.

PMID- 16910430
TI  - The beginner's guide to the medical malpractice deposition.

PMID- 16910431
TI  - Saving Medicaid.

PMID- 16910432
TI  - Major and complex reconstructions challenge physicians.

PMID- 16910433
TI  - Presidential inauguration address "The other side of the story".

PMID- 16910434
TI  - Craniosynostosis: A review for the non-surgeon.

PMID- 16910435
TI  - Climbing the reconstructive ladder in the head and neck.
AB  - This article will give the reader an overview of the techniques used to
      reconstruct surgical, traumatic or congenital defects of the head and neck. The
      reconstructive ladder concept is used to provide a framework for understanding
      these techniques, from the simplest to the most complex, with the highest
      priority given to selecting the procedure that will provide restoration of form
      and function with the least risk.

PMID- 16910436
TI  - Surgical options for facial reanimation.
AB  - Facial palsy has devastating functional and psychosocial sequelae for patients,
      thus its treatment requires thorough understanding of state-of-the-art modalities
      that can optimize facial reanimation. Treatment depends on the mechanism and
      timing of injury, patient goals, overall health, and motivation. Because of its
      significant impact on patient's quality of life, both acute and long-standing
      deficits should be addressed. Often requiring multi-disciplinary efforts, an
      institution well-equipped in dealing with facial reanimation offers patients the
      most consistent results.

PMID- 16910438
TI  - Breast augmentation.

PMID- 16910437
TI  - The S.O.F.T. Cheek method: an approach to lower eyelid and midface rejuvenation.
AB  - Procedures to rejuvenate the lower eyelids and cheek are amongst the most common
      aesthetic surgeries performed today. Rejuvenation should be individualized based
      on the patients concerns, anatomic deformity, and medical condition. A balanced
      and natural clinical result often requires a combination of techniques designed
      to address each patient's individual pattern of aging, while maximizing patient
      safety. We present the S.O.F.T. Cheek method of analysis and treatment, which
      utilizes well-developed principles and techniques, to consistently maximize
      clinical results and patient satisfaction.

PMID- 16910439
TI  - Breast reconstruction following mastectomy.
AB  - There are numerous reconstructive options for patients undergoing mastectomy for
      breast cancer. These include autologous tissue transfer and implant
      reconstruction. Various factors play a role in determining the appropriate
      reconstructive course including the type of cancer resection and patient
      characteristics including comorbidities, smoking, body habitus, and patient
      preference. Patient education is an important component to minimizing the
      psychological trauma and emotional stress that accompanies treatment for breast
      cancer. All patients with breast cancer should be aware of their reconstructive
      options.

PMID- 16910440
TI  - Update on the evaluation of wrist pain.
AB  - Wrist pain is a common presenting complaint in patients both for the hand
      specialist and the primary care physician. Knowledge of wrist anatomy and a
      thorough and systematic wrist examination remain the mainstays of evaluation.
      Radiologic as well as arthroscopic technology and techniques continue to evolve
      and provide useful adjuncts to wrist evaluation that expand our diagnostic and
      therapeutic capabilities.

PMID- 16910441
TI  - Atrial fibrillation in athletes.
AB  - A 60-year old male physician on staff at North Kansas City Hospital was admitted
      with paroxysmal atrial fibrillation. The physician is an avid long-distance
      runner. Ultimately, three other male physicians on staff, all long-distance
      runners, were identified as having lone atrial fibrillation. This prompted a
      literature search which initially indicated a higher than normal incidence of
      atrial fibrillation in endurance and elite athletes. However, recent data has
      questioned the validity of this observation. The management of the athlete with
      atrial fibrillation poses special concerns and can be problematic. The incidence,
      causes, implications, and management of atrial fibrillation in athletes is the
      subject of this review.

PMID- 16910442
TI  - Migraine mimics stroke in a young woman.

PMID- 16910443
TI  - [Infant "starting formulas" are not all equal: comparative analysis of
      nutritional characteristics].
AB  - Infant formulas on the market today represent the only available alternative to
      breast milk for infants of those women who are unable to continue breastfeeding
      through the first year of life, and are planned to allow artificially fed infants
      for approaching the structural and functional effects observed in breastfed
      infants. Within this context, the functional outcome of the breastfed infant
      (particularly as far as growth and development) well represent the gold standard.
      For this purpose, the following compounds have been added to starting infant
      formulas (planned for the first six months of life, when human milk should
      represent the exclusive dietary source) in recent years: long-chain
      polyunsaturated fatty acids (LCPUFA), for brain composition and neurodevelopment,
      probiotics and prebiotics for the fecal flora and the local intestinal defense,
      and nucleotides for promoting the immune response. Changes in protein quantity
      and quality allow to balance the blood amino acids pattern (possibly relevant to
      the early stages of brain development for the neurotransmitter function) and
      reducing the protein intake could be important for the prevention of later
      overweight. Hydrolysed proteins may be relevant in the prevention of atopic
      disorders. Many trials have been published so far with short-term assessment,
      nevertheless, we need more data on the long-term follow-up of infants who were
      fed the new formulas to fully understand the role of these functional compounds
      on the neural performance, the prevention of overweight and obesity and the
      development of the immune-allergic pattern.

PMID- 16910444
TI  - [Diagnostic and etiopathogenic aspects of autism].
AB  - The Pervasive Developmental Disorders are a very complex and discussed subject
      both from a clinical point of view and about the etiopathogenesis. Different
      opinions have generated, in the past, different classification systems based on
      the underlying theoretical hypothesis. Nowadays the most popular classification
      systems are the ones contained in the DSM-IV and in the ICD-10. They define these
      diseases as "conditions characterized by a distortion of base development
      regarding verbal and non-verbal communication, the reciprocal and social ability
      of interaction and the imaginative activity." Inside this scenery are also
      compromised the motion activity, the awareness, the sensorial perception, the
      humour and the knowledge ability. About the pathogeny, nowadays many authors
      think autism is based on particular biological conditions, nevertheless they are
      not well-known or general. The exact origins of the rise of autistic disease are,
      in fact, still hypothetical. In the same way the concatenation of pathological
      events determining the arise of such a complex and wide clinical condition is
      also hypothetical. The discussion is mainly about the classification of childhood
      autism as a pure organic pathology or as a final expression of organic, psychic,
      familiar and social factors correlating with wrong operating structures,
      differentiated from an anatomic and functional point of view. So it seems quite
      plausible to take into account the possibility of a multisystemic compromise
      likely generated by a multifactor condition.

PMID- 16910445
TI  - [Neonatal toxic erythema : clinico-epidemiologic characteristics and recent
      pathogenic hypothesis].
AB  - Erythema toxic neonatorum (ETN) is a common, self-limiting condition of term
      infants, appearing particularly within the first 48 hours of life. ETN has a
      worldwide distribution, with a frequency variable from 19% to 72%. Erythematous
      macules, wheals, papules and pustules in varying combination occur, with crops of
      lesions waxing and waning and spontaneous resolution within hours to days. It's
      important the differential diagnosis from other pustular neonatal conditions,
      some of which are severe. The etiology of ETN remains unknown. Recent studies
      reveal an activation of immune cells in the lesions of ETN and a high presence of
      peptide antibiotics, suggesting that ETN is an inflammatory skin reaction to the
      microbial colonization at birth.

PMID- 16910446
TI  - [Burn injuries of children in first aid care].
AB  - Burn injury are second leading cause of accidental death in children. Treatment
      of burns depends on severity of injury, location, characteristics of child and
      mechanism of injury. Objective is to value the multiple problems in infant burns
      and immediate management in emergency room. The better and immediate treatment
      burns recover and prevent dirty scars.

PMID- 16910447
TI  - [Perinatal risk factors for infection in the newborn. Multicenter clinico
      epidemiologic investigation].
AB  - The neonate, in particular if preterm, has a specific immunological system that
      makes him/her more susceptible to infections which are still a major cause of
      mortality and morbidity. The early onset infective patterns are often vertically
      transmitted from the mother to the fetus in the perinatal period. Some mother
      conditions like genitourinary infections, pre-delivery fever, PROM, pPROM,
      preterm delivery, abortions, fetal demise are important neonatal risk factors.
      The role of these factors as causes of early onset neonatal infections was
      evaluated by an Italian multicentric epidemiologic investigation supported by the
      MIUR. Mothers admitted to obstetrician hospitals for parturition were studied in
      a case control retrospective analysis. Mothers presenting with the selected risk
      factors were the cohort of cases while the admissions without risk factors next
      to each case represented the controls. The following risk factors were considered
      for analysis: 2nd trimester abortion, PROM, pPROM, preterm delivery and fetal
      demise. Eight hospitals entered the multicentric research and 29610 patients have
      been analyzed: 2466 PROM, 478 pPROM, 946 preterm delivery, 244 abortions, 133
      fetal demise. Every woman received a microbiological screening by cervico-vaginal
      and rectal swab and/or urine culture. As much as 3892 cases from the University
      Hospitals of Parma and Torino concern, the cervicovaginal swab was positive in
      76.5% pPROM, in 50.6% PROM and 50.5% preterm deliveries. The positivity of the
      swabs showed statistical relevance in cases compared to controls. In cases
      presenting with abortion the frequency of positive cultures (44.1%) was higher
      than the controls, but it did not reach statistical relevance. Conversely,
      positivity of cultures was lower in cases with fetal demise than control group
      but without statistical difference. In the cohort of 675 women selected from our
      Institute (University of Parma) the overall rate of positivity of cervico-vaginal
      swabs was about 44% and only one germ was isolated in 94.6% cases: 49,8% Gram
      positive and negative, 14.1% Streptococcus hemolyticus B group, 34.7% Candida.
      The rate of cultural tests performed before delivery was statistically higher in
      cases than controls (74.3% vs 23.2%, p < 0.001). Furthermore 14.3% newborns from
      mothers in the case group and 2.3% newborns from mothers in the control group
      were admitted to the neonatal care unit. Among them 8.4% and 1.2% respectively
      needed antibiotics while 0.4% and 0.2% respectively presented with early onset
      infection. Ear swabs were performed in 48,8% of infants born to mothers from the
      case group and in 26.9% of infants born to mothers from the control group, in
      6.5% and in 2.9% respectively were the skin swabs performed as well. No
      statistical difference was met. The choice to perform cultural examinations was
      statistically higher in cases than controls, but the positivity rate was similar
      in both groups, perhaps because of a more specific choice in the control group.
      CONCLUSION: our data confirm the relationship between infections and preterm
      delivery, PROM, pPROM and support the hypothesis that infections might be the
      cause of these conditions and not simply an association. A prompt maternal
      microbiological control during pregnancy and delivery, especially in women
      presenting with known risk factors, gives the possibility to do early diagnostic
      therapeutic interventions and to minimize the frequency and severity of early
      sepsis in newborns.

PMID- 16910448
TI  - [Neonatal transport service in emergency : Lombardia's experience].

PMID- 16910449
TI  - [Angioma of the lip in pediatric age].

PMID- 16910450
TI  - [Prevention of dental caries].
AB  - Caries prevention. Today there is enough scientific knowledge about the etiology
      of caries and factors that might interfere in this process in order to develop
      preventive strategies. Pathological factors including acidogenic bacteria (e.g.
      mutans streptococci and lactobacilli), salivary disfunction and dietary
      carbohydrates are related to caries progression. Protective factors--which
      include salivary calcium, phosphate and proteins, salivary flow, fluoride, and
      antibacterial components or agents--can balance, prevent or reverse dental
      caries. Two strategies have been described in preventive medicine: (1) the
      population strategy, which in aimed at a general reduction of the risk factors
      for all the individuals in the population, whether diseased or not; (2) the high
      risk strategy, which aims at targeting the program at those individuals with the
      highest risk. As caries progression or reversal is determined by the balance
      between protective and pathological factors, caries prevention should be given
      high priority not only by physicians (general, paediatric, paediatric dentist)
      but also by schools and even the governmental authorities. More time should be
      spent giving the right informations to the population regarding dietary habits
      and programs of nutritional education, oral hygiene routines and fluoride
      exposure.

PMID- 16910451
TI  - [The child with suspect acute appendicitis in emergency care].
AB  - Acute appendicitis is the most common acute abdominal pain in childhood.
      Appendicitis is rare during the first two years of life and uncommon before the
      age of five years. The rarity, coupled with the preschool inability to cooperate
      in history and physical examination, explain why more than 90% of children under
      five years of age with appendicitis are already complicated by the laparatomy is
      undertaken. The aim of this study is to evaluate the prediction of the marks left
      by appendicitis.

PMID- 16910453
TI  - [Kearns-Sayre syndrome].

PMID- 16910452
TI  - [Prenatal diagnosis of pelvic floor malformations].
AB  - Pelvic floor malformations are congenital defects in the pelvic and perineal
      area, which are derived from a defective development of the cloaca membrane, the
      uro-rectal septum, the mesonephric and para-mesonephric ducts and the urogenital
      sinus. These are complex anomalies with a profound emotional impact on parents.
      The prenatal diagnosis is possible favoring the prenatal counseling for the
      parents and expediting the post-natal evaluation and management. Aim of the
      present paper is to review the current criteria for the prenatal diagnosis of the
      following malformations: anorectal anomalies, cloacal anomalies, persistence of
      the urogenital sinus, bladder and cloacal exstrophy and ambiguous genitalia.

PMID- 16910454
TI  - Main results of a national multicenter study assessing the compliance of
      pediatric centers to Italian Society of Neonatology recommendations on prevention
      of respiratory syncytial virus infection.

PMID- 16910455
TI  - Compliance of pediatric centers to Italian Society of Neonatology recommendations
      on prevention of respiratory syncytial virus infection: results of the second
      season of the Previeni Study.

PMID- 16910456
TI  - [Vaginal swab in pediatric age].
AB  - Vaginal secretion sampling in young patients. The aim of the study was to
      evaluate whether different instrumental tools (the classical cotton swab, the
      urethral cotton swab, the balloon shape cotton swab and cyto-brush) yield
      different sampling success in young patients presenting with suspected
      vulvovaginitis. The study was conducted in a randomised prospective way on 100
      children with symptoms of vulvovaginal infection (age range: 4 months -8 years )
      seen at the Clinic of Paediatric Gynaecology of the Department of Obstetric and
      Gynaecology, "V.Buzzi" Children's Hospital, Milano (Italy). Children's compliance
      and the number of samples which had to be discontinued, because of children's
      intolerance have allowed the evaluation of each tools. Each of these tools was
      tested on 25 young patients. The vaginal secretion sampling was not possible on 8
      patients out of 25 with cyto-brush (32%), on 7 out of 25 with the balloon shape
      cotton swab (28%), on 4 out of 25 with the classical cotton swab (16%) and only 1
      out of 25 with the urethral cotton swab (4%). In conclusion all the instruments
      tested allow sampling of vaginal secretion in young children, but the reaction
      and compliance of the patients has been best with the otologic cotton swab.

PMID- 16910457
TI  - [The sclero-atrophic lichen as principal cause of acquired phimosis in pediatric
      age].
AB  - Lichen sclerosus et atrophicus is main cause of phimosis in pediatric age and
      require surgical therapy. This one, characterized by partial circumcision
      followed by topical treatment with steroids, is safe and effective.

PMID- 16910458
TI  - [Cardiovascular involvement in new born of HIV positive mothers].

PMID- 16910459
TI  - [Utility and safety endoscopic digestive procedure in pediatric age].
AB  - The aim of this study is to verify the utility and safety of endoscopic
      procedures in the evaluation of children with clinically-significant
      gastrointestinal symptomatology. We report our experience of 87 pediatric
      endoscopy procedures including esophagogastroduodenoscopy, colonoscopy and tissue
      biopsies performed in 85 infants, children and adolescent, 3 months-15 years old,
      over a two-year period, june 2002-november 2004 after complete history, physical
      examination and basic investigations. General anesthesia was used in all patients
      after informed consent obtained from parents. Non significant complications were
      observed in this series of patients. In 81 cases (92.5%) with clinical symptoms
      and laboratory indications for gastrointestinal disease, the endoscopy and
      bioptical samples confirmed the utility and safety of procedure. Coeliac disease
      (39 cases), gastritis (11 cases), esophagitis (6 cases) were the most common
      organic cause of upper gastrointestinal disease. Allergic and indeterminate
      colitis (7 cases) were the most common cause of lower gastrointestinal disease.
      In 4.7% the procedures appear to be particularly helpful in the diagnosis of
      inflammatory lesions of the esophagus and stomach. In summary, the data
      demonstrate that endoscopy techniques show low morbidity, provide important
      diagnostic informations in pediatric gastrointestinal diseases and can be done
      safely in patients over 3 months of age.

PMID- 16910460
TI  - [Genetic basis in chronic interstitial familial pneumopathy. Familial study of
      SFTPC].
AB  - Mutations in the gene encoding surfactant protein C (SP-C) SFTPC have been found
      to be associated with chronic interstitial lung disease. A 5-year-old girl oxygen
      dependent from birth and affected by interstitial lung disease (ILD) is
      heterozygous for a T to C change in exon 3 resulting in the substitution of
      threonine for isoleucine at codon 73 (173T), already described in association
      with ILD. We studied 25 members of her family where the 173T mutation in the SP-C
      gene is associated to chronic pulmonary diseases. Five members in the mother's
      family showed respiratory diseases with great diversity in clinical features: her
      mother was affected by restrictive pneumopathy and emphysema, her grand-mother by
      asthma and recurrent pneumonia, 2 uncles underwent lung transplantation in the
      adult age, an aunt was clinically diagnosed having pulmonary fibrosis. All the
      family members affected by pulmonary diseases and one with no clinical symptoms
      showed the presence of the mutation 173T. Among the other family members the
      mutation was found in six subjects for whom no clinical data were available, yet.
      Our results confirm that heterozygosity for the mutation 173T may cause chronic
      inflammation of the lung or progressive pulmonary fibrosis. In addition, the
      possibility to study a large pedigree allowed us to perform a genotype-phenotype
      correlation indicating a marked phenotypic variability. The diversity in
      symptoms, age at onset, clinical course, duration of lung disease in the
      relatives sharing this mutation indicates an incomplete penetrance of the
      mutation. This might be due to the influence of other genetic factors thus
      indicating that the phenotype may be complicated by additional components.

PMID- 16910461
TI  - [Angiomatous meningioma and epilepsy in a 2.6-years-old girl].
AB  - A case of meningo-angiomatosis (MA), in a 2.6 -years-old girl with refractory
      focal and secondary generalized seizures, starting at the age of 2 years, is
      presented. MRI evaluation revealed a lesion located at the left temporal lobe;
      the patient underwent surgical intervention. Histology revealed the lesion to
      have the features of MA.

PMID- 16910462
TI  - [Congenital megacystis in a female fetus. Case report].
AB  - The Authors report a case of congenital megacystis without other anomalies,
      diagnosed in a 27GW female fetus. At prenatal counselling the diagnostic
      hypothesis formulated were obstructive uropathy (cloacal malformation, uro
      genital sinus, urethral atresia), functional alteration (neurogenic bladder,
      primitive myopathies) or Prune Belly Syndrome (rare in females). The outcome
      following treatment suppose a visceral myopathy, for this condition, however
      definitive etiology is obscure.

PMID- 16910463
TI  - [West Nile fever and West Nile encephalitis].

PMID- 16910464
TI  - [HIV encephalopathy and neural stem cell virology].

PMID- 16910465
TI  - [Influenza-associated encephalopathy].

PMID- 16910466
TI  - [Worms that get on our nerves].

PMID- 16910467
TI  - [The neural mechanisms underlying "smart brains"].

PMID- 16910468
TI  - [Retrovirus infection and neurological disorders].

PMID- 16910469
TI  - [A case of isolated CNS sarcoidosis with diffuse confluent high intensity lesions
      at bilateral deep white matter].
AB  - We reported a 60-year-old woman who suffered from isolated neurosarcodosis. She
      was presenting comprehensive dysfunction and intermittent high fever. In several
      months she gradually developed dysorientation, amnesia, dementia. However, no
      focal sign such as paralysis or sensory disturbance was demonstrated. Her blood
      chemistry showed normal including ACE (angiotensin converting enzyme) and
      lysozyme. Cerebrospinal fluid revealed elevated mononuclear cells, protein, and
      decreased glucose level. At first we treated with antibiotics including antiviral
      drugs in suspect of the infectious encephalomeningitis. But no improvement was
      observed. The elevation of ACE in spinal fluid made us suspect of
      neurosarcoidosis. So intravenous predonizoron (1,000 mg) was given, improving.
      Her high fever and mental disturbance improved. Second spinal fluid showed
      improvement. During the course her brain MRI revealed new bilateral diffuse
      confluent high intensity lesions at the deep white matters. Brain biopsy of deep
      matter at the right anterior lobe showed noncaseating granuloma. Since systemic
      work-up to detect sarcoidosis did not reveal lesions other than CNS, we
      considered this patient as having isolated CNS sarcoidosis.

PMID- 16910470
TI  - [A cases of schizencephaly associated psychosis].
AB  - Schizencephalyis a rare disorder of brain development resulting in the formation
      of abnormal unilateral or bilateral clefts in the cerebral hemispheres. One
      patient is described with psychotic symptoms with unilateral schizencephaly. The
      implications of the association between schizencephaly and psychosis in these
      patients for understanding the biology of the psychoses are discussed.

PMID- 16910471
TI  - [A case of myasthenia gravis appearing after thymomectomy: with histopathological
      investigation].
AB  - We report a 64-years old man who had myasthenia gravis (MG) appearing after
      surgical removal of thymoma. His thymoma was not removed completely due to
      adhesion with other organs. Histopathologicaly, the thymoma was an invasive and
      predominantly epithelial type. CD45RO positive cells increased in the thymus.
      After five months of thymectomy, he received radiation therapy because the
      remaining tumor grew up slightly. The radiation was effective, and the recurrence
      of tumor has never been detected after that. However, nine months after the
      surgery, he noticed ptosis and double vision, and he was diagnosed as MG because
      of positive serum anti-AchR antibody and positive Tensilon test. He received oral
      prednisolone, and he has kept a good condition. Previous reports have shown that
      an extensive thymectomy tends to reduce the incidence of post-operative MG. In
      our case, the remaining thymoma might increase the risk of MG. And the removed
      thymus might contain an unknown regulatory factor that could inhibit a
      development of MG. The risk factor for development of post-operative MG should be
      investigated in future.

PMID- 16910472
TI  - [Listeria monocytogenes meningoencephalitis lacking meningeal signs].
AB  - We report a fatal case of meningoencephalitis due to Listeria monocytogenes. A 74
      year old alcoholic man presented with high-grade fever lasting for four days
      without headache and meningeal signs. Routine blood analysis showed leukocytosis,
      but serum C-reactive protein (CRP) was not significantly elevated. He developed
      altered consciousness with focal seizure, and cerebrospinal fluid (CSF)
      examination showed a minor degree of pleocytosis, elevated protein, and
      hypoglycorrhachia. Repeated CSF examination four days later showed greater
      increases in cells and proteins as well as severely decreased glucose level.
      Bacterial culture from the initial CSF showed a growth of L. monocytogenes.
      Meningoencephalitis caused by L. monocytogenes may have atypical clinical and
      laboratory features, and should be listed in the differential diagnosis of
      immunocompromised or elderly patients presenting with fever of unknown origin
      associated with altered consciousness.

PMID- 16910473
TI  - [Posttraumatic subarachnoid hemorrhage: traumatic or aneurysmal?].

PMID- 16910474
TI  - [Preload and ventricular lusitropism; logistic and monoexponential function
      fittings].
AB  - A logistic function has been found to fit the isovolumic left ventricular (LV)
      relaxation pressure curve and the isometric relaxation force curve of the
      papillary muscle much more precisely than the conventional monoexponential
      function. Therefore, the logistic time constant (tauL) has been proposed as a
      better index of the rate of cardiac relaxation or lusitropism than the
      conventional monoexponential time constant (tauE). Many investigators have
      reported that tauE changes with preloading. We analysed and compared the effect
      of LV volume (LVV) loading on both logistic and monoexponential fittings and
      their time constants of the isovolumic LV relaxation pressure curve in the
      excised, cross-circulated canine hearts. We found that the logistic fitting was
      superior to the monoexponential fitting at any LVV. LVV loading did not affect
      tauL at all but affected tauE slightly. The logistic fitting more reliably
      characterises the lusitropism than the monoexponential fitting, and tauL, serving
      as a more reliable ventricular lusitropism index, is independent of changes in
      LVV loading or the Frank-Starling effect.

PMID- 16910475
TI  - [Effects of sevoflurane and propofol on neuromuscular blocking action of Org 9426
      (rocuronium bromide) infused continuously in Japanese patients].
AB  - BACKGROUND: The purpose of this study was to investigate the interaction of
      anesthetic agents with Org 9426 (rocuronium bromide) infused continuously. The
      effect of intubation dose of Org 9426 on its infusion rate was also investigated.
      METHODS: Total of 38 Japanese patients were randomly allocated either to receive
      intubation dose of 0.6 or 0.9 mg x kg(-1) of Org 9426. These patient groups were
      anesthetized with either sevoflurane or propofol. Infusion of Org 9426 was
      started with the initial infusion rate of 7 microg x kg(-1) x min(-1) when T1
      reappeared after the intubation dose. The infusion rate was adjusted to keep the
      height of T1 between 3-10% of the control value. RESULTS: The rates of infusion
      90 min after the start of infusion were 3.4, 7.5, 3.9 and 7.7 microg x kg(-1) x
      min(-1) for the 0.6 mg x kg(-1)-sevoflurane, 0.6 mg x kg(-1) propofol, 0.9 mg x
      kg(-1)-sevoflurane and 0.9 mg x kg(-1) propofol groups, respectively. Sevoflurane
      significantly reduced the infusion rate with both intubation doses. The mean
      infusion rates of 0.9 mg x kg(-1) groups were slower than those of 0.6 mg x kg(
      1) groups up to 60 min after the start of infusion. Mean clearance of Org 9426
      during infusion was not different between sevoflurane and propofol anesthesia.
      CONCLUSIONS: Patients receiving sevoflurane anesthesia required a markedly lower
      Org9426 infusion rate compared with patients receiving propofol anesthesia.

PMID- 16910476
TI  - [Epidural infusion of low dose bupivacaine after combined spinal-epidural
      anesthesia using needle through needle method provided no analgesic effect on
      postoperative pain after caesarian section].
AB  - BACKGROUND: In order to evaluate the analgesic efficacy of low dose epidural
      bupivacaine infusion with and without morphine after caesarean section we
      performed combined spinal-epidural anesthesia (CSEA) using needle through needle
      method. Three different epidural analgesic regimens were compared
      retrospectively. METHODS: The number of analgesic use during 24 hours after
      operation was compared. Patients were categorized into three groups; group N :
      intraoperative bolus epidural morphine (2.5 mg) alone, group L : bolus morphine
      (2.5 mg) plus epidural bupivacaine infusion (32 ml of 0.2% bupivacaine) at a rate
      of 2.1 ml x hr(-1), group M : bolus morphine (2.4 mg) plus epidural bupivacaine
      morphine (33 ml of 0.2% bupivacaine containing morphine 2.3 mg) infusion at a
      rate of 2.1 ml x hr(-1). Used analgesics included pentazocine 15 mg i.m.,
      diclofenac 25 mg suppo. and loxoprofen 60 mg p.o.. RESULTS: The mean number of
      analgesic use during the first 24 hours in group M (0.29 +/- 0.46) was
      significantly smaller than those of group N (0.97 +/- 0.91) and group L (0.84 +/-
      0.95). Percentage of patients requiring no analgesic during the first 24 hours
      was significantly less in group M (70.8%) than in group N (33.4%) and group L
      (42.1%). CONCLUSIONS: A 2.1 ml x hr(-1) infusion of epidural bupivacaine has no
      analgesic effect after caesarean section under CSEA using NTN method.

PMID- 16910477
TI  - [Prophylactic effects of neutrophil elastase inhibitor for patients undergoing
      surgery for thoracic aortic aneurysm: a retrospective study].
AB  - BACKGROUND: Systemic inflammatory response syndrome (SIRS) can occur after
      cardiac surgery under cardiopulmonary bypass (CPB), especially thoracic aortic
      surgery. Several reports have suggested that the earlier neutrophil elastase
      inhibitor (NEI) is used, the more dramatically the acute lung injury (ALI)
      following SIRS can be improved. We therefore examined whether prophylactic
      administration of NEI is effective in treating ALI following SIRS. METHODS: In a
      retrospective study, 24 patients were divided into a control group and a NEI
      group, for whom infusion of NEI 0.2 mg x kg(-1) x hr(-1) was started prior to
      initiation of CPB. We compared PaO2/FIO2 (P/F) ratio, intubation time, ICU stay,
      and numbers of intubated patients and patients admitted to the ICU between the
      two groups. We also examined laboratory findings for the two groups related to
      systemic inflammation and organ function. RESULTS: In the NEI group, P/F ratio
      tended not to be exacerbated postoperatively, which might have been responsible
      in part for the finding that intubation time and ICU stay were significantly
      shorter and ratios of intubated patients and those staying in the ICU were
      significantly lower in the NEI group. Laboratory findings in the two groups
      fluctuated similarly. CONCLUSIONS: Prophylactic administration of NEI appears to
      be useful for achieving early extubation and discharge from the ICU of patients
      undergoing thoracic aortic surgery.

PMID- 16910478
TI  - [Comparison of pentazocine and fentanyl in total intravenous anesthesia using
      propofol].
AB  - BACKGROUND: Pentazocine may be an alternative for fentanyl during total
      intravenous anesthesia (TIVA) using propofol. The authors compared the efficacy
      and safety of pentazocine for analgesics in TIVA using propofol. METHODS: Eighty
      nine patients scheduled for mastectomy were analyzed retrospectively. Patients
      were classified into two groups by used analgesics; pentazocine (Group P, n = 34)
      and fentanyl (Group F, n = 55). Anesthesia was induced with propofol, using
      target controlled infusion method, and ketamine 20-50 mg, and was maintained with
      propofol infusion and increments of fentanyl or single dose of pentazocine with
      40% oxygen in air. Postoperative pain was assessed using a visual analogue pain
      scale (VAS). RESULTS: There were no differences in the patient background between
      both groups. Systolic as well as diastolic blood pressure and heart rate were not
      different between both groups during surgery. The maintenance dose of propofol
      was not different between the two groups. Awakening time in about 80% of patients
      was within 15 minutes and is not different between the two groups. There were no
      differences between the two groups regarding VAS. There are no severe
      complications. Incidence of nausea and vomiting was not different between the two
      groups. CONCLUSIONS: The results suggest that pentazocine would provide a stable
      hemodynamic state, rapid recovery and an effective postoperative pain relief to
      the same degree as with fentanyl in TIVA with propofol.

PMID- 16910479
TI  - [Arterial to end-tidal carbon dioxide tension difference during laparoscopic
      colorectal surgery].
AB  - BACKGROUND: Determination of end-tidal carbon dioxide pressure (PET(CO2)) is
      effective to confirm adequate ventilation, because arterial to end-tidal carbon
      dioxide tension difference (deltaa-ET(CO2)) does not change normally during
      operation. But deltaa-ET(CO2) may change during laparoscopic surgery, because
      peritoneal insufflation of CO2 will increase CO2 production and reduce functional
      residual volume. Changes in deltaa-ET(CO2) were reported in laparoscopic
      cholecystectomy with cardiovascular complication, but there is controversy about
      how deltaaET(CO2) will change in more complicated and long laparoscopic surgery.
      In this prospective study, we examined changes in deltaa- ET(CO2) during
      laparoscopic colorectal surgery. METHODS: Fifty patients received combined
      general and epidural anesthesia. CO2 pneumoperitoneum was initiated after
      obtaining arterial blood for gas analysis. Mechanical ventilation was used to
      maintain PET(CO2) at a stable value between 30 and 40 mmHg during the procedure.
      Arterial blood gas analysis was performed 10, 60, 120 minutes after CO2
      insufflation, and 10 minutes after the termination of insufflation. RESULTS: The
      mean +/- SD for deltaa-ET(CO2) was 5.8 +/- 4.1 before pneumoperitoneum, 7.1 +/-
      4.8, 8.1 +/- 5.4, 6. 4 +/- 4.9 in 10, 60, 120 minutes after pneumoperitoneum, and
      6.4 +/- 4.9 in 10 minutes after the termination of pneumoperitoneum. deltaa
      ET(CO2) increased significantly during pneumoperitoneum, but did not increase
      further even if CO2 insufflation was longer than 60 minutes. CONCLUSIONS: In
      laparoscopic colorectal surgery, Pa(CO2) should be checked for at least the first
      60 minutes to confirm adequate ventilation.

PMID- 16910480
TI  - [Prolonged paralysis after long-term administration of vecuronium in the
      intensive care unit].
AB  - A 51-year-old woman with renal failure requring hemodialysis received a total of
      446 mg of vecuronium over a period of 4 days to help mechanical ventilation and
      developed generalized muscle weakness after its discontinuation. It took 2 wks to
      wean her from mechanical ventilation and 3 wks for her to be able to walk. She
      did not receive drugs which might alter neuromuscular transmission such as
      corticosteroid and aminoglycoside antibiotics. Electromyogram and nerve
      conduction studies were normal. We believe that the cause is the accumulation of
      vecuronium and active metabolites due to renal failure. The case suggests that we
      should minimize the duration of neuromuscular block in patients with renal
      failure by aggressive use of sedatives and analgesics and the optimization of
      ventilator settings.

PMID- 16910481
TI  - [Pharmacokinetic simulation of high-dose administration of dexmedetomidine for
      decubitus treatment].
AB  - We used only dexmedetomidine to sedate a patient with Alzheimer disease,
      Parkinson's syndrome and emaciation for decubitus treatment in the prone
      position. The infusion rate of dexmedetomidine without a loading dose was
      increased until sufficient sedation was attained. The maximum plasma
      concentration and the plasma concentration in a stable state, which were
      calculated by pharmacokinetic simulation analysis, were 2.3 ng x ml(-1) and 1.5
      ng x ml(-1), respectively. Respiration disorder did not occur and hemodynamic
      stability was preserved despite administration up to 11.5 mcg x kg(-1) x h(-1).
      An increase in the dose per weight was needed to increase the absolute dose
      because of emaciation. It was found by pharmacokinetic simulation analysis that
      the plasma concentration of dexmedetomidine required for decubitus treatment
      might be higher than the plasma concentration considered to be necessary for
      sedation in intensive care units. The simulation was conducted to administer
      dexmedetomidine, to estimate hemodynamic reaction, and to estimate the necessary
      plasma concentration. We conclude that dexmedetomidine is useful as an anesthetic
      agent for decubitus treatment in the prone position, although further
      investigations with regard to its safety are required.

PMID- 16910482
TI  - [Clinical experience of tracheal intubation using Trachlight in patients with
      unstable dentition].
AB  - BACKGROUND: Trachlight is a light-tipped stylet designed to guide tracheal
      intubation. It obviates the need for direct laryngoscopy and is reported to be
      particularly useful for managing difficult tracheal intubation. Its clinical
      application, however, is not limited to difficult airway management. METHODS:
      Here we report our experience of the use of Trachlight in 64 adult patients who
      were at risk of dental injury during direct laryngoscopy because of unstable
      teeth around the incisors or severe alveolar disease. RESULTS: Of 64 patients (33
      men and 31 women) aged between 30 and 85, the trachea was successfully intubated
      using Trachlight without dental damage in 63 patients. In 1 patient, a tracheal
      tube was smoothly placed, but a tooth was injured after the removal of the
      stylet. No other complications associated with the use of Trachlight were noted.
      CONCLUSIONS: Our experience suggests that Trachlight can be a helpful tool for
      intubation in patients having dental problems. Because of the blind nature of the
      technique, but preexisting lesions of the larynx and vocal cords might be
      overlooked in intubation using Trachlight. Further investigation is warranted to
      recommend Trachlight as a intubation technique of choice in patients with
      unstable dentition.

PMID- 16910483
TI  - [Pulmonary edema due to upper airway obstruction after extubation].
AB  - We report a patient who developed pulmonary edema due to airway obstruction after
      extubation. A 22-year-old man underwent removal of the nails for thoracoplasty
      under general anesthesia combined with epidural anesthesia. Upper airway
      obstruction occurred after extubation. SpO2 decreased to 70%. Insertion of an
      oral airway relieved the airway obstruction. However, inspiratory wheezing was
      heard over both lung fields. Chest X-ray taken 90 minutes after the event
      revealed pulmonary edema. Pulmonary edema gradually resolved after intravenous
      furosemide and oxygen inhalation by mask.

PMID- 16910484
TI  - [Anesthetic management for cesarean section in a patient with moyamoya disease].
AB  - A 28-year-old female patient with moyamoya disease after hemorrhage into the
      cerebral cavity, and a history of an indirect blood-circulation reconstruction
      surgery at 19 years of age, was scheduled to undergo cesarean section at 34 weeks
      of gestation because of pregnancy toxemia. No symptoms and no abnormal shadow
      with MRI were observed preoperatively. To avoid intracranial hemorrhage and
      cerebral infarction, epidural anesthesia was performed. No complication was
      observed during and after the cesarean section.

PMID- 16910485
TI  - [Pulmonary artery obstruction in a pediatric patient during removal of a right
      ventricular myxoma].
AB  - Cardiac myxoma, especially right ventricular myxoma is very rare. We report a 2
      year-old girl who underwent the emergent surgical resection of a right
      ventricular myxoma. She was noticed to have systolic murmur and was referred to
      our hospital. Echocardiography and magnetic resonance imaging (MRI) revealed the
      presence of tumor extending from the right ventricle across the pulmonic valve
      into the pulmonary artery. Anesthesia for the removal of a right ventricular
      myxoma should be carried out carefully, because pulmonary tract obstruction may
      occur during the procedure. During the removal of the tumor, the tumor obstructed
      the pulmonary artery resulting in severe decrease of the blood pressure and the
      heart rate. Because pulmonary artery occulusion occurred after pericardiotomy,
      chest massage was started quickly and in 15 minutes cardiopulmonary bypass was
      established. The tumor was removed completely and was diagnosed as myxoma by
      histological examination. The patient recovered uneventfully and was discharged
      without complications.

PMID- 16910486
TI  - [Case of traumatically bleeding shock patient rescued by using an aortic
      occlusion balloon catheter during surgery].
AB  - A 55-year-old (163 cm, 70 kg) man with traumatic intra-abdominal bleeding
      underwent emergency operation. The patient was in a state of hemorrhagic shock
      with 82 mmHg of systolic blood pressure (SBP) at hospital arrival. His condition
      became severer within about 1 hr, and tracheal intubation and mechanical
      ventilation were consequently started in the ambulatory emergency room. SBP
      decreased to 60 mmHg when he was transferred to the operating room. Anesthesia
      was induced with intravenous fentanyl and vecuronium, and was maintained with
      inhalation of sevoflurane in 50% oxygen. After laparotomy, it was impossible to
      detect the bleeding source because of a large quantity of hemorrhage. To reduce
      the blood loss, aortic occlusion balloon catheter (AOBC) was inserted into the
      upper abdominal aorta via the right femoral artery. Aortic occlusion was
      performed twice each for twenty minutes. The evelation of SBP and decrease of
      bleeding dose were secured by aortic occlusion. Thereby the source of bleeding
      could be detected and surgical procedure could be finished with survival of the
      patient. The insertion of AOBC for the surgical patient with intra-abdominal
      hemorrhagic shock may be advantageous for uncontrollable bleeding.

PMID- 16910487
TI  - [Accidental use of suxamethonium for general anesthesia in a patient with
      hereditary hypocholinesterasemia that was not recognized preoperatively].
AB  - We experienced an accidental use of suxamethonium for general anesthesia in a 26
      year-old woman with hereditary hypocholinesterasemia that had not been recognized
      preoperatively. The patient was scheduled for total colectomy as her chronic
      ulcerative colitis could not be controlled with medications. Routine preoperative
      screening such as blood cell counts, biochemical data, chest x-ray and
      electrocardiogram were performed but serum cholinesterase (ChE) activity was not
      measured. As the preoperative patient condition was good with no abnormal
      history, anesthesia was induced and maintained with propofol, ketamine and
      fentanyl as usual. For muscle relaxation, suxamethonium was used for tracheal
      intubation, and vecuronium was used for the maintenance. After surgery,
      postanesthetic course was uneventful. One year later, as the patient was pregnant
      and scheduled for cesarean section, the preoperative screening was done. The
      biological data showed a hypocholinesterasemia without liver dysfunction. Thus,
      previous medical records of internal medicine were cheked. Surprisingly the
      record showed hypocholinesterasemia when she was 15 and 21 years of ages.
      However, as the physicians did not recognize hypocholinesterasemia, they did not
      inform the patient of it. Why did the patient have no prolonged apnea and
      emergence after the previous anesthesia? As the surgical time was exceeded 4 hrs,
      plasma suxamethonium could fortunately be less than its effective concentration
      at emergence. However, this case strongly suggests us that preoperative screening
      should be done without any omission. In addition, if serum ChE activity is not
      examined, use of suxamethonium should be avoided.

PMID- 16910488
TI  - [Method of evading the overshoot phenomenon of transcutaneous P(CO2) measurement
      at the ear lobe].
AB  - BACKGROUND: Kagawa et al. confirmed the overshoot of transcutaneous P(CO2)
      (Ptc(CO2)) during the early stage of measurement with Ptc(CO2) monitor (TOSCA,
      Linde Medical Sensors AG, Basel, Switzerland). We examined the method to evade
      this phenomenon. METHODS: Eight adult patients under general anesthesia were
      examined. Two probes were mounted each on the left and right ear lobes after
      constant end expiratory P(CO2) had been obtained for ten to fifteen minutes. One
      P(CO2) probe was set at 42 degrees C. Another one was set at 45 degrees C for the
      first 15 minutes and then decreased to 42 degrees C. RESULTS: With the probe
      heated at 42 degrees C, overshoot was observed in 5 out of 8 cases, the peak of
      which is 44 +/- 5.5 mmHg at 8.2 +/- 1.1 minutes and then these values went down
      to 39 +/- 4.0 mmHg at 19 +/- 1.3 minutes and stayed stable. Probes heated at 45
      degrees C and placed on the opposite side did not show this phenomenon and were
      stabilized at 5 +/- 0.9 minutes. CONCLUSIONS: With this apparatus, we found that
      it is effective to avoid overshoot to heat the probe at 45 degrees C and to
      change at 42 degrees C after 15 minutes.

PMID- 16910489
TI  - [Morphological findings in MRI to be considered in perfoming spinal and epidural
      anesthesia].
AB  - The spinal cord and cauda equina move in the subarachnoid space by changing
      positions. The subarachnoid space is compressed from the dorsal side by epidural
      injection. At the end of gestation, the subarachnoid space is compressed from the
      ventral side by the engorged venous plexus. Idiopathic epidural lipomatosis is
      observed almost exclusively in the obese population. In the case of lipomatosis,
      the subarachnoid space is compressed by increased extradural fat around the
      thecal sac. We have had some severe cases of spinal canal stenosis in whom it is
      difficult to perform the spinal puncture. The authors showed some MR images and
      discussed morphological issues for spinal or epidural anesthesia.

PMID- 16910490
TI  - [Incidence and characteristics of perioperative pulmonary thromboembolism in
      Japan in 2004].
AB  - BACKGROUND: The incidence of perioperative pulmonary thromboembolism (PTE) is
      reported not to be low in Japan. The aim of this study is to investigate the
      incidence and characteristics of perioperative PTE in Japan in 2004. METHODS: A
      questionnaire was mailed to 960 institutions registered as the teaching hospitals
      of the Japanese Society of Anesthesiologists (JSA). The survey details included
      age, sex, type of surgery, and risk factors of patients operated in 2004.
      RESULTS: Effective responses were received from 642 institutions (66.9%) of 960
      institutions. A total of 409 cases of perioperative PTE were reported from 245
      institutions (25.5% of the institutions responded). The incidence of
      perioperative PTE was 3.62 per 10,000 cases. Cardiac arrest occurred at the onset
      in 65 cases (15.9%). Of the patients, 150 (36.7%) had malignancy; 142 (34.7%)
      were obese; and 121 (29.6%) were bed-ridden (> 4 days). In 273 cases (66.7%), the
      patients were over 60 years of age. PTE was found to be more frequent in females
      than in males (males, 147 cases; females, 259 cases). The types of surgery
      resulted in perioperative PTE with high frequency were "spinal surgery" (6.95 per
      10,000 cases) and "limbs and/or hip joint surgery" (9.79 per 10,000 cases).
      Eighty-nine patients (21.8%) died from perioperative PTE. CONCLUSIONS: The
      incidence of perioperative PTE was not low and its mortality was high in Japan in
      2004. In particular, the incidence of perioperative PTE was found to be high in
      females, the elderly, patients with malignancy, and patients who had undergone
      orthopedic surgery.

PMID- 16910491
TI  - [Preoperative assessment of microvascular decompression for hemifacial spasm with
      fusion imaging of 3D MR cisternogram/angiogram].
AB  - The preoperative assessment of microvascular decompression (MVD) for hemifacial
      spasm has been performed with MRI, but assessment of the compressive status by 2D
      imaging has a number of limitations. We used a fusion image of the 3D MR
      cisternogram and co-registered 3D MR angiogram, reconstructed from MR
      cisternogram, obtained by 3D fast spin-echo sequence, and MR angiography, 3D time
      of-flight and spoiled-gradient recalled sequences, for the preoperative
      assessment of the offending artery in 10 patients with hemifacial spasm. The
      anatomical relationship of the nerve-vessel complex was assessed on the simulated
      images, and compared with the intraoperative findings. The fusion image of the 3D
      MR cisternogram/angiogram depicted contours of the brain, nerves, and vessels
      clearly, and that allowed precise assessment of the pathogenic compression of the
      facial nerve by the offending vessels, comparative to the operative findings. The
      fusion imaging of the 3D MR cisternogram/angiogram may provide useful information
      in the surgical planning of MVD for hemifacial spasm.

PMID- 16910492
TI  - [Percutaneous vertebroplasty for vertebral compression fracture].
AB  - BACKGROUND: Percutaneous vertebroplasty has become an option for the treatment of
      painful osteoporotic compression fractures in patients in whom conservative
      medical management has failed. AIM: This paper assessed the effectiveness and
      safety of percutaneous vertebroplasty in patients with focal pain caused by
      compression vertebral body fractures. MATERIALS AND METHODS: Over a twenty-five
      month period 63 patients underwent percutaneous vertebroplasty, and ten of these
      patients were subsequently retreated, for a total of 73 operations on 93
      vertebrae. The patients were affected by osteoporotic compression fractures
      (n=57) or by benign or malignant infiltrative processes (n=6). All patients were
      examined at discharge and thereafter to assess the level of pain and investigate
      possible changes in the quality of life. The mean length of follow-up was 15.2
      months. RESULTS: After treatment, almost 90% of patients reported complete
      disappearance or significant alleviation of the pain. In 7 of 63 of the patient
      (11%) there were small asymptomatic leakages of cement outside the vertebral
      body. A substantial number of patients with osteoporosis, 19% of the study
      population, experienced new fractures following treatment with vertebroplasty.
      DISCUSSION: Our experience confirms the effectiveness of vertebroplasty to pain
      caused by vertebral fractures. If the indications are strictly followed,
      improvement of symptoms is often immediate, allowing the return of mobility, and
      patient satisfaction with surgery is higher. The use of appropriate systems
      limits the number of complications.

PMID- 16910493
TI  - [Diagnostic value of perfusion-weighted MRI for evaluating postoperative
      alteration of cerebral hemodynamics following STA-MCA anastomosis in patients
      with moyamoya disease].
AB  - OBJECTIVE: Surgical revascularization for moyamoya disease prevents cerebral
      ischemic attacks by improving cerebral blood flow (CBF). But little is known
      about the changes of CBF and its effect on neurological status during the acute
      stage after direct bypass for moyamoya disease. METHODS AND RESULTS: Perfusion
      weighted magnetic resonance imaging (PWI) by the SE-EPI method was performed 4
      and 10 days after superficial temporal artery-middle cerebral artery (STA-MCA)
      anastomosis on 11 sides of 9 patients (male:female = 2:7, 24-61 years old) with
      moyamoya disease. All patients underwent single-photon emission computed
      tomography (SPECT) 1 and 7 days after surgery. The time-to-peak (TTP) by PWI
      showed focal decrease at the site of the anastomosis 4 days after STA-MCA
      anastomosis compared to preoperative TTP, and was further decreased in larger
      territory 10 days after surgery in all patients. Postoperative cerebral blood
      volume (CBV) by PWI showed significant increase compared to preoperative CBV in
      four patients who suffered symptomatic cerebral hyperperfusion after surgery.
      Postoperative SPECT revealed apparent increase of CBF in all patients and the
      patency of the STA-MCA bypass was confirmed by MRA. All patients were discharged
      without neurological deterioration compared to preoperative neurological status,
      and none of them suffered ischemic attack after surgery. CONCLUSION:
      Postoperative decrease in TTP by PWI could be a sensitive parameter for the
      normalization of CBF after STA-MCA anastomosis in patients with moyamoya disease.
      Postoperative increase in CBV may suggest cerebral hyperperfusion and could be
      the optimal predictor for hyperperfusion syndrome after STA-MCA anastomosis in
      patients with moyamoya disease.

PMID- 16910495
TI  - [A case of Sturge-Weber syndrome with severe temper tantrum].
AB  - We report a case of Sturge-Weber syndrome with intractable epilepsy presenting
      complex partial seizures(CPSs) and severe temper tantrum successfully treated
      with anterior temporal lobectomy. A 23-month-old girl without facial angioma
      presented with seizures from 8 months after birth. Neuroradiological examination
      demonstrated angioma in the left temporooccipital lobes and calcification in the
      left occipital lobe. Thus she was diagnosed as having Sturge-Weber syndrome. Her
      parents sought medical advice because of intractable and more frequent CPSs and a
      change in temperament manifesting as severe temper tantrums. Interictal
      electroencephalogram (EEG) showed relatively mild abnormal slow wave discharges
      in the left temporal region. The patient underwent left anterior temporal
      lobectomy based on intraoperative electrocorticography (ECoG) findings.
      Histopathological examination demonstrated gliotic change in the amygdala. After
      the surgery, she has remained seizure-free for 14 months while taking
      anticonvulsants and temper tantrums ultimately showed remission 10 months
      following surgery. This case may indicate that severe temper tantrum was
      associated with a change in amygdala structures.

PMID- 16910494
TI  - [Intraoperative photodynamic diagnosis for spinal ependymoma using 5
      aminolevulinic acid: technical note].
AB  - OBJECTIVE: The fluorescence-guided resection using 5-aminolevulinic acid (5-ALA)
      is a well established method for the treatment of brain tumor, especially
      malignant glioma. However, there is no report on photodynamic diagnosis (PDD) for
      spinal tumor. In the present study, we evaluated the usefulness of PDD for spinal
      ependymoma using 5-ALA. METHODS: Three patients with spinal ependymoma received
      oral doses of 5-ALA (20 mg/kg body weight) 2 hours before anesthesia induction.
      Intraoperatively, fluorescence was observed with a 420 nm sharp cut filter after
      excitation with a violet semiconductor laser (405 nm) and was verified by
      analysis of fluorescent spectra. Residual fluorescent samples taken from the
      tumor cavity were examined histologically RESULTS: Fluorescence peaked at 636nm
      in the removed tumors in all cases. Fluorescent tissue tended to exist at the
      cranial and caudal portion in the tumor cavity or around the anterior median
      fissure. The residual fluorescent tissue was not detected after removal of the
      tumor in case 1. The residual fluorescent tissue was composed of tumor cells and
      ependymal lining in case 2 or the infiltrated inflammatory cells and vascular
      endothelial cells in case 3. Postoperative magnetic resonance (MR) imaging showed
      no residual tumor in any of the cases. CONCLUSION: The results of this study
      indicate the usefulness of 5-ALA-induced tumor fluorescence in guiding resection
      of spinal ependymoma. 5-ALA-induced porphyrin fluorescence may label spinal
      ependymomas easily and clearly enough to enhance the completeness of tumor
      removal.

PMID- 16910496
TI  - [A case of petrotentorial meningioma presented as an acute subdural hemorrhage].
AB  - The authors report a rare case of petrotentorial meningioma presenting as acute
      subdural hematoma. A 60-year-old female was introduced to our hospital
      complaining of sudden headache and gait disturbance. CT and MRI demonstrated a
      petrotentorial tumor with a subdural hematoma in the posterior fossa. The tumor
      was enhanced intensively on MRI and showed the dural tail sign. The patient
      developed progressive impairment of consciousness along with hydrocephalus. After
      ventricular drainage, emergency intracranial decompression through hematoma
      evacuation and partial tumor resection was performed. One month later, she
      improved clinically and the tumor resected totally in the second craniotomy.
      Histological examination showed a meningothelial meningioma with high vascularity
      in part. She recovered uneventfully and was discharged on foot. We discussed the
      etiology of an acute subdural hematoma caused by intratumoral hemorrhage and
      reviewed past literatures.

PMID- 16910497
TI  - [Primary intraosseous cavernous hemangioma in anterior clinoid process].
AB  - Primary intraosseous cavernous hemangiomas (PICHs) are rare tumors, and there are
      no previous reports of cases with a tumor at the anterior clinoid process. We
      report a case of a PICH at the anterior clinoid process in a 66-year-old female
      presenting with headaches and visual impairment. CT and MR imaging showed a mass
      in the anterior clinoid process. The lesion showed hyperintensity on T1- and T2
      weighted imaging, and gadolinium was homogenously enhanced. The lesion was
      removed surgically, and histologically confirmed as a cavernous hemangioma.
      Preoperative examinations could not provide a definitive diagnosis. A brief
      clinical and radiological review of the literature is presented.

PMID- 16910498
TI  - [CNS sarcoidosis presenting with intracerebral hemorrhage: case report].
AB  - Sarcoidosis is a systemic, chronic inflammatory disease characterized by non
      caseating epithelioid granuloma. It is well known that the central nervous system
      (CNS) is also involved in about 5% of patients with systemic sarcoidosis.
      Although CNS sarcoidosis presents with various neurological manifestations,
      intracerebral bleeding is quite rare. In this report, we describe a case in which
      a patient suffered from intracerebral hemorrhagic due to CNS sarcoidosis. A 57
      year-old male who had been diagnosed as having systemic sarcoidosis was admitted
      to our hospital due to status epilepticus. Plain CT scan showed a subcortical
      hematoma in the left marginal gyrus. Serial MR imaging revealed that an enhanced
      mass in the overlying cortex had gradually increased its size. Subsequently, the
      enhanced mass and hematoma were totally removed, using a navigation system.
      Pathological examination revealed typical findings of sarcoidosis. We discuss the
      mechanism of intracerebral bleeding due to CNS sarcoidosis in this report.

PMID- 16910499
TI  - [A middle cerebral artery dissecting aneurysm manifesting solely with pain,
      following a vertebral artery dissecting aneurysm].
AB  - A 41-year-old male had presented with severe neck pain and was diagnosed as
      having a left vertebral artery (VA) dissecting aneurysm. During the observation
      period, he suddenly suffered from a pain on his left temple. MR imaging revealed
      neither SAH nor cerebral infarction. MR angiography, computed tomographic (CT)
      angiography and cerebral angiography showed fusiform dilatation of the M1 portion
      of the left middle cerebral artery (MCA) which had been normal in the former
      study. The abnormality of the left MCA normalized on both MR and CT angiography 6
      months after the second onset. Because of the chronological change of
      radiological findings compatible with the symptom, we diagnosed the second
      episode as a MCA dissecting aneurysm manifesting with isolated pain. Among the
      previous forty-four MCA dissecting aneurysms, all but one case presented with
      hemorrhagic or ischemic event. In addition, this is the only case of multiple
      dissecting aneurysms of VA and MCA manifesting with isolated pain.

PMID- 16910500
TI  - [A case of encapsulated intracerebral hematoma mimicking metastatic brain tumor].
AB  - We report a case of encapsulated intracranial hematoma (EIH) mimicking metastatic
      brain tumor. A 77-year-old male with a medical history of prostate cancer was
      admitted to our hospital presenting with progressive left hemiparesis. Previous
      head CT scan and MRI findings during 3 weeks before admission revealed a
      subcortical acute to subacute hematoma under the right precentral gyrus with
      growing perifocal brainedema. The Head DSA showed tumor-stain with vascular
      compression corresponding to the hemorrhagic mass, and Tl-201 SPECT study
      revealed high L/N ratio (3.0) and high L/E ratio (0.8). The preoperative
      diagnosis was metastatic brain tumor originating from prostate cancer, and total
      removal of the mass was undergone with the postoperative diagnosis of EIH.
      Neither tumoral component nor vascular malformation was found even by detailed
      pathological study. EIH is a rare variant of intracranial hemorrhage and most of
      cases in past reports are preoperatively misdiagnosed as malignant brain tumor.
      In our case, even Tl-201 SPECT and DSA, which are reported as key studies for
      distinguishing EIH from other brain tumors, demonstrated brain tumor-like
      findings. It is necessary to consider the possibility of EIH when we encounter
      hemorrhagic mass in the brain parenchyma even with brain tumor-like
      radiographical images.

PMID- 16910501
TI  - [Operative neurosurgery: personal view and historical backgrounds (1). EC-IC
      bypass].
AB  - This series on surgical technique of neurosurgery contains following topics: EC
      IC bypass, aneurysm-AVM surgery, surgery of deep seated tumors such as
      craniopharyngioma, pineal region tumors, surgery of skull base tumors,
      intramedullary spinal cord tumors, amygdalohippocampectomy and others. They are
      originating from author's personal point of view based on his experience and are
      presented with various techniques learnt from my teachers and colleagues from
      different countries also mentioning related anecdotes and historical backgrounds.
      In this issue, presented are the topics about training of microsurgical
      anastomosis in the laboratory along with belonging techniques and instruments,
      clinical STA-MCA bypass, OA-PCA bypass and interposition graft bypass including
      "bonnet" bypass.

PMID- 16910502
TI  - [Off-pump coronary artery bypass via median sternotomy].
AB  - Off-pump coronary artery bypass grafting (off-pump CABG: OPCAB) is a useful
      technique of coronary revascularization in terms of reduction of operative
      mortality and morbidity. Because the biggest advantage of OPCAB may be that it
      can prevent perioperative stroke, we selected patients for OPCAB based on the
      preoperative evaluation of neck and intracranial vessels. We could totally
      eliminate intraoperative stroke in patients undergoing OPCAB, although some
      patients with a severe neck vessel disease developed postoperative
      stroke/transient ischemic attack in an early postoperative period (the 4th
      approximately 8th postoperative day) mostly due to thrombosis from the diseased
      vessel. Therefore, high-risk patients with a severe neck vessel disease should be
      treated with a more aggressive anticoagulation protocol postoperatively. As for
      the quality of grafting, the number of graft, the rate of complete
      revascularization, and early graft patency were comparable between OPCAB and CABG
      with a cardiopulmonary bypass. The long-term results in terms of freedom from
      cardiac death and cardiac events were also comparable. We conclude that we could
      achieve less invasiveness in coronary revascularization by using an OPCAB
      technique without compromising the quality of grafting.

PMID- 16910503
TI  - [Clinical impact of partial sternotomy for off-pump coronary artery bypass].
AB  - History of cardiopulmonary bypass has been the pursuit for less invasiveness.
      Currently, about 60% of primary coronary artery bypass grafting is performed as
      off-pump coronary artery bypass (OPCAB). We tried to determine whether OPCAB by
      the lower partial sternotomy could be safely performed in the elderly patients
      with the age equal to or over 80 years. The number of grafts was 2.4 +/- 0.8 in
      patients with partial sternotomy (PS) and 2.3 +/- 0.9 in patients with full
      sternotomy (FS). Postoperative duration of mechanical ventilation in patients
      with PS was significantly shorter than that in patients with FS (p <0.05).
      Although the differences were not significant, the incidence of wound and
      respiratory complications were less in patients with PS than in those with FS.
      Theoretically, tracheostomy and percutaneous cricothyroidotomy can be safely
      performed in the early postoperative period after PS. Early ambulation can
      decrease the complications related to prolonged bed rest. Because dislocation of
      the sternoclavicular joint and/or brachial plexus injury do not occur, upper
      extremity movement remains unrestricted and shoulder pain does not occur. Our
      results suggested that OPCAB using PS could become the standard procedure in the
      elderly patients with multiple risk factors.

PMID- 16910504
TI  - [Endoscopic off-pump coronary artery bypass].
AB  - Since 1999, we have performed total endoscopic off-pump coronary artery bypass
      (OPCAB). Innovation of endoscopic optic techniques and development of endoscopic
      forceps were necessary to perform this procedure. The operative methods of the
      endoscopic OPCAB; a 12 mm port for 3-D endoscope is firstly inserted through the
      5th intercostal space (ICS) in the mid axillary line, and then the left internal
      thoracic artery (LITA) is taken down in semi-skeletonized fashion using other 2
      instrumental 5 mm ports (the 3rd, 6th anterior axillary ICS). To anastomose LITA
      to the left anterior descending artery (LAD), other 2 10 mm and 12 mm ports are
      inserted through the 4th ICS in parallel. A conventional end-to-side anastomosis
      is manually performed with 8-0 prolene. The average LITA harvesting time and
      anastomotic time have been shortened significantly thanks to the endoscopic
      innovation. However, there are some limits to manual manipulations in the
      endoscopic OPCAB. Robotic surgery might have more advantages to the flexibility
      of forceps tips. The introduction of robotic surgery system is indispensable to
      safe and certain endoscopic OPCAB.

PMID- 16910505
TI  - [Arrested coronary artery bypass grafting with modified percutaneous
      cardiopulmonary support circuit (mini-pump system)].
AB  - Therapeutic strategy for ischemic heart disease has been changing in this decade.
      We attempted to improve the conventional extracorporeal circulation with the aim
      of less invasive coronary artery revascularization. Our extracorporeal
      circulation has been used since 2002, and called the 'mini-pump system' or 'MECC
      (minimized extracorporeal circulation) system'. The mini-pump system has a
      centrifugal pump, a membrane oxygenator, a soft reservoir and the characteristics
      of low prime volume completely closed circuit and low volume cardioplegia. We
      investigated the degree of invasiveness of the mini-pump system by examining the
      clinical outcomes (minimum hematocrit, the amount of transfusion and so on),
      thrombin-antithrombin III complex (TAT), complement factor (C3a) and interleukin
      (IL)-10 levels. The mini-pump system demonstrated better value than the
      conventional extracorporeal circulation (TAT; 19.5 : 66.1 ng/ml, C3a; 1,349 :
      1,895 mg/dl, IL-10; 105 : 486 pg/ml, respectively) and proved to be less
      invasive. The incidence of postoperative atrial fibrillation using the mini-pump
      system was less than that of the conventional extracorporeal circulation. In this
      issue we presented the vista of the mini-pump system by showing how it decreased
      invasiveness.

PMID- 16910506
TI  - [Endoscopic radial artery harvesting].
AB  - The radial artery is a popular arterial conduit for coronary artery bypass
      grafting (CABG). However, the traditional open harvesting technique requires a
      long incision, and is therefore associated with some wound complications and
      cosmetic problems. In order to solve them, we introduced the endoscopic radial
      artery harvesting (ERAH) at our institution in February 2004 utilizing the
      VasoView system. The ERAH technique was performed as safely as the traditional
      open technique and the harvested radial arteries were acceptable as CABG
      conduits. In particular, patients are satisfied with the excellent cosmetic
      results of the procedure. Herein, we focus surgical technique, complications of
      ERAH and ways to prevent them by describing our initial experience and short-term
      clinical follow-up of the ERAH patients.

PMID- 16910507
TI  - [Off-pump coronary artery bypass with endarterectomy].
AB  - The diffusely diseased left anterior descending coronary artery (LAD) remains a
      challenge for both interventional cardiologists and cardiac surgeons. We assessed
      the surgical outcomes obtained from off-pump coronary artery reconstruction, with
      or without endarterectomy, for a diffusely diseased LAD. One hundred and eighteen
      patients were treated with an extended LAD reconstruction, with or without
      endarterectomy. The left internal thoracic artery (LITA) was used to reconstruct
      the LAD in all patients. Coronary artery reconstruction was performed without
      endarterectomy in 63 patients and with endarterectomy in 55 patients. The
      operative mortality was 0.8%. Perioperative myocardial infarction was observed in
      14.4% of the patients. The mean LAD incision length was 5.6 +/- 1.4 cm. The
      patency rate of the LITA to LAD was 96.2% by early angiographic examination.
      Coronary artery reconstruction, with or without endarterectomy, using the LITA
      for a diffusely diseased LAD can be performed with acceptable results.

PMID- 16910508
TI  - [Minimally invasive cardiac surgery using port-access method].
AB  - From October 1997 to January 2006, we operated on 209 patients with port-access
      cardiac surgery. The patients were 116 with atrial septal defect (ASD), 85 with
      mitral valve disease, 2 with coronary artery bypass grafting (CABG), 10 with
      other (ventricular septal defect, partial endocardial fusion defect, myxoma). The
      average of postoperative hospital stay is 7 (shortest: 3) days. None of these
      patient have been readmitted, however, there was 1 mortality. The operative
      technique for ASD is established in this series. On the other hand, for mitral
      valve disease, a modification point such as prevention of a complication and
      shortening of cardiopulmonary bypass time were recognized. It seemed that careful
      determination of operative indication and establishment of security were
      important. Improvement and development of operative technology of port-access
      method will enable future safe total endoscopic or robotic cardiac surgery. In
      this paper, we report the latest surgical technique of port-access cardiac
      surgery.

PMID- 16910509
TI  - [Aortic valve replacement through a partial sternotomy].
AB  - BACKGROUND: Instead of a median sternotomy which has been accepted as the
      standard approach to cardiaovascular surgery, we have selected a partial
      sternotomy as a minimally invasive surgery since 1997. Every technique and device
      must be reevaluated because the entire heart cannot be easily assessed. METHOD:
      In this paper we reported the pitfalls and results of 108 cases of aortic valve
      replacement through an upper and lower partial sternotomy. Single surgeon had
      used the single technique through the same operation field from 1997 to 2005.
      RESULTS: Mortality rate was 1.9% (2 patients). Aortic cross clamp time was a
      little longer in this series than in the conventional median sternotomy group.
      There were no differences in operating time, pumping time, intubation duration or
      bleeding. ICU stay and hospital stay were shorter in this series than in the
      conventional sternotomy group. The operating time was shorter in the
      regurgitation group than in the stenosis group. There were no differences in
      pumping time, intubation duration, bleeding, ICU stay or hospital stay.
      CONCLUSION: The minimally invasive cardiac surgery for the aortic valve
      replacement could be routinely and safely indicated.

PMID- 16910510
TI  - [Minimally invasive cardiac surgelry for congenital heart diseases].
AB  - We have performed 174 pediatric open-heart operations using a lower midline skin
      incision and a minimal sternotomy approach since 1996. There was no death or
      major complication caused by this approach, and the resulting scar in each
      patient is difficult to be seen under an ordinary undershirt. The technique of a
      lower mid-line skin incision and minimal sternotomy approach is a safe, reliable
      and cosmetically advantageous method for a pediatric cardiac operation. We have
      applied an autologous blood predonation protocol in pediatric open-heart surgery
      since 1996. The study included 103 children weighing 7.5 kg or more. 8 ml/kg of
      blood was taken twice before operation. 97 patients (94.2%) needed no homologous
      blood transfusion during cardiopulmonary bypass. We consider our protocol of
      autologous blood predonation to be safe and effective for avoiding homologous
      blood transfusion in pediatric patients. Twelve children with patent ductus
      arteriosus (PDA) were successfully treated by thoracoscopic surgery under
      transesophageal echocardiography, by which interruption of the ductal flow was
      confirmed. Video-assisted endoscopic surgery can be safely applied to pediatric
      patients with PDA. This technique may be an effective addition to the staged
      management of more complex forms of congenital heart defects. To minimize
      deleterious postoperative influences of cardiopulmonary bypass on the pulmonary
      circulation, the right heart bypass operation was achieved without use of
      cardiopulmonary bypass. Four patients in whom no intracardiac procedure was
      needed, have undergone this operative maneuver using a temporary bypass. This
      operative procedure is especially recommended for pulmonary atresia with intact
      ventricular septum with sinusoidal communication when decompression of right
      ventricular pressure might cause coronary steel and ischemia.

PMID- 16910511
TI  - [Robotically and video-assisted thoracoscopic interruption of patent ductus
      arteriosus].
AB  - Over the past decade, video-assisted thoracoscopic techniques have been used in
      the pediatric population. Recently, the computer-enhanced robotic system has been
      applied to video-assisted thoracoscopic interruption of patent ductus arteriosus
      (VATS-PDA). We focused on the utility of a voice-controlled robotic arm
      (automated endoscope system for optimal positioning: AESOP 3000) in VATS-PDA.
      Thirteen infants weighing 4.2 approximately 12.6 (mean 6.6) kg underwent
      robotically assisted VATS-PDA. Robotically assisted VATS-PDA is comparable with
      closure by means of the conventional video-assisted thoracoscopic technique.

PMID- 16910512
TI  - [Endovascular stent-graft repair for thoracic aortic aneurysm].
AB  - Endovascular stent-grafting holds great potential as a minimally invasive
      alternative to open surgery for thoracic aortic aneurysm. Although there have
      been several commercially available stent graft systems applied to abdominal
      aortic aneurysm in the United States, Gore TAG is the only device that is
      approved by Food and Drug Association (FDA) for thoracic aortic aneurysm repair.
      Experience of endovascular aneurysm repair by our homemade system and TAG device
      which is crafted particularly for the thoracic aorta is reported. TAG was
      successfully delivered to the target region in 137 patients (98%). The aneurysm
      was successfully excluded by our homemade system in 258 patients (94%). The
      mortality rates of TAG and our homemade device groups were 2.1 and 3.6%
      respectively. Postoperative stroke incidence was 1.8% and was more frequent in
      patients with stent-graft deployed in the region between the landing zone map of
      Z3 and Z4. The rate of paraplegia/paraparesis with delayed onset was 2.8% in TAG
      group, and was almost similar in the homemade group (2.6%). The event-free rate
      of patients treated with stent-graft was low as compared to that of open surgery
      in 1 and 3 year follow-up period. Endovascular stent-grafting is feasible as one
      treatment option for thoracic aortic aneurysm. Selection of proper indications,
      development of the better device and technical improvement are keys to successful
      stent-grafting.

PMID- 16910513
TI  - [Transluminal stent-graft placement for the treatment of acute aortic
      dissection].
AB  - We have performed transluminal stent-graft placements (TSGPs) to seal the primary
      entry site to treat and prevent complications of aortic dissection since 1997.
      Sixty patients with a primary intimal tear in descending aorta underwent TSGP.
      TSGP was performed in 27 acute onset dissections (AOD) with dissection-related
      complications instead of emergency surgery. Fourteen AOD without complications
      were treated to prevent aneurysmal enlargement. Nineteen chronic dissections were
      treated to prevent rupture. TSGP was technically successful in all cases. The
      hospital mortality rate was 4.9% in AOD and 0% in chronic dissections. The
      primary success rate was 87.8% in AOD. After hospital discharge, 2 patients died
      during an average follow-up of 56.2 months. Actuarial survival rate at 5 years
      was 90.0% in AOD. We conclude that TSGP is a reasonable treatment option for
      aortic dissection. However, intimal tear formations caused by the stent-graft is
      a problem that requires further developments of stent-grafts.

PMID- 16910514
TI  - [Catheter intervention for congenital heart diseases].
AB  - Percutaneous closure of ostium secundum atrial septal defects (ASD) has been
      widely accepted and is becoming one of the standard treatments for this
      malformation. Among several devices, the Amplatzer Septal Occluder seems to
      provide the highest level of effectiveness and safety. Transcatheter ASD closure
      has been increasingly used in recent years with high success rates. The complete
      closure rate immediately after the procedure was 91.2%, and 97.1% 1-year after
      the procedure. However, some complications have been reported with the use of
      this device, such as arrhythmia, embolization, thrombus formation, pericardial
      effusion, atrioventricular block and cardiac erosion. Since the initial report by
      Cambier and colleagues, clinical experiences with transcatheter closure of the
      patent ductus arteriosus using Gianturco coils have increased rapidly. Cook
      detachable coil has the advantage that retrieval of coil is possible up to the
      moment of its release from the delivery wire. Thus, this detachable coil may have
      some technical benefits to occlusion of relatively larger diameter ductus
      arteriosus. There is also a 0.052 inch Gianturco coil. It contains more Dacron
      fibers, which contributes to high closure rate. Thus, it is used for larger
      patent ductus arteriosus and adult patients. Amplatzer Duct Occluder, which is
      not yet available in Japan, is reported to provide high success rate even in the
      large ductus.

PMID- 16910515
TI  - [Endovascular stent-grafting of ruptured aortic aneurysms].
AB  - Ruptured thoracic aortic aneurysms expose the patient to a major risk of death
      and remain a therapeutic challenge. Hemorrhage control and prevention of fatal
      bleeding are primary treatment goals in this medical emergency. Early
      postoperative mortality of surgically treated patients is estimated to be still
      high. An increasing number of reports on successful endovascular treatment of the
      ruptured thoracic aortic aneurysms by endovascular stent-grafting have been
      published, and they provide better early results. Since 2002, 59 patients with
      thoracic aortic aneurysms have been treated with the endovascular technique using
      stent-graft in our institute. Initial success of stent-grafting, which means
      exclusion of the aneurysms without endoleak, were achieved in 98.3%. Treatment
      using stent-grafting for ruptured thoracic aortic aneurysms (13/ 59) also
      presented satisfactory early outcome. Endovascular stent-grafting is a low
      invasive and useful treatment for ruptured thoracic aortic aneurysms, and is
      strongly recommended if the aneurysms are morphologically susceptible.

PMID- 16910516
TI  - [Total arch graft implantation with open stent-graft placement for aortic arch
      aneurysm or dissection].
AB  - We have developed and routinely performed the total arch graft implantation with
      open stent-graft placement for aortic arch aneurysm or dissection. This method is
      easy and respiratory-troubleless method, because of ascending and arch
      replacement with 4 branched graft and descending graft implantation with stent
      graft from opened aortic arch. This method is useful for the patient with aortic
      arch diseases concomitant with coronary artery bypass candidate, respiratory
      dysfunction and aortic dissection.

PMID- 16910517
TI  - [Practice and education in thoracoscopic surgery].
AB  - There are 2 vectors in training in thoracoscopic surgery. One is a paradigm in
      which training is patterned on education in laparoscopic surgery centered on
      young surgeons, and the other is a paradigm in which introduction of
      thoracoscopic surgery is promoted among thoracic surgeons who are already active
      on the front line. Although the demand, degree of need, and content of each of
      these paradigms differ, the ultimate goal is the same. Thus, it is important to
      prepare a system that combines safer operations and less invasive surgical
      techniques, and haste is being made to prepare a society-initiated program.
      Publication of thoracoscopic surgery techniques that overcomes the barriers of
      university and school and support of technical standards are desirable, and we
      think that achieving this will be linked to the standardization of techniques.

PMID- 16910518
TI  - [Minimally invasive surgery for lung cancer using thoracoscope as a 'microscopic
      surgery'; for the safety endoscopic surgery].
AB  - Video-assisted thoracoscopic surgery (VATS) is now turned to be common procedure
      for lung cancer treatment, however, controversy still remains regarding to its
      adequacy and safety. We developed VATS procedure aiming at 'the equality to
      traditional open thoracotomy'. Important points to perform VATS are (1) incisions
      are placed to facilitate converting to open thoracotomy if necessary, (2)
      surgical operator positions at the anterior side of patient lying lateral
      decubitus position, (3) using instruments for open thoracotomy, or making new
      instruments for VATS which can utilize for open thoracotomy either, (4) the
      endoscope is held by instrument, not by hand, to keep proper position. Surgical
      operator performs VATS watching at the television monitor, not through the
      incision, (5) to divide vessels, such as pulmonary artery or vein, ligature by
      silk threads is usually put at the proximal side of transecting vessel.
      Underlying difference between VATS and open thoracotomy is simply the way of
      approach to the pleural cavity. Appropriate skills and instruments are required
      to perform a kind of 'microscopic surgery', so that operators are sure to perform
      adequate operation for lung cancer including en bloc nodal dissection at VATS
      safely.

PMID- 16910519
TI  - [Modern radical resection for lung cancer; a critique on the video-assisted
      radical resection].
AB  - The modern radical resection for the lung cancer consists of the parenchymal lung
      resection at least by tumor-bearing lobe and hilar/mediastinal lymph node
      dissection. For minimally invasive intent, the curative resection is being
      performed under video-thoracoscopy. The relative advantage over the conventional
      procedure under thoracotomy has yet to be defined in terms of operative
      indicators, postoperative pain, safety, cost, and so on. No previous study has
      ever clearly described the significant difference between these 2 procedures. The
      present thoracotomy-based radical resection has been fully down-sized together
      with advanced instrumentations, and the perioperative parameters between 2
      procedures remained minimal. The evidence-based advantage of video-assisted
      radical resection needs to be addressed. Since their differences are solely
      concerned about the route of the approach into the thoracic cavity, the
      oncological difference reasonably does not seem to exist.

PMID- 16910520
TI  - [Minimally invasive thoracotomy for the lung resection; without thoracoscopic
      procedure].
AB  - Video-assisted thoracoscopic surgery (VATS) is though to be a minimally invasive
      surgical procedure of lung resection. But there are some problems still remained
      about training, cost efficacy and oncological principles. Minimally invasive
      thoracotomy without thoracoscopic procedure was reviewed in this paper. In case
      of standard posterolateral thoracotomy with cutting ribs, it brings less
      postoperative pain and less dislocation of the ribs that fixes the ribs with
      bioabsorbable poly-L-lactide (PLLA) pins. Muscle sparing thoracotomy is available
      in broadly peeling off the muscle of trapezius and latissimus dorsi
      subcutaneously. But sometime much exudate collects subcutaneous wound in
      postoperative period so that some trouble or complication often occurs in the
      management of postoperative course. In case of axilloanterior thoracotomy we have
      proper view which is almost the same as standard posterolateral thoracotomy
      without cutting thoracic muscles. Skin incision runs from the axillar to the
      lateral margin of the breast and the 4th or 5th intercostal thoracotomy is
      performed through thoracodorsal muscle being pressed laterally, anterior serratus
      muscle being split. There is no need to cut the ribs, and good for the upper or
      middle lobectomy and the upper mediastinal dissection. Axilloanterior thoracotomy
      is minimally invasive than standard posterolateral thoracotomy and is useful for
      the surgery of upper or middle lobe lung cancer. In the procedure of thoracotomy
      operating with or without thoracoscope is not to be concerned. Important is to
      perform operation smoothly in adequate time for patients ease.

PMID- 16910521
TI  - [Thoracoscopic surgery for pneumothorax].
AB  - It is difficult to tell clearly what a therapy for pneumothorax is because it is
      not enough just to cut away the bullae. The patients should be treated mentally,
      physically and less invasively. The 4 anxieties should be solved for pneumothorax
      patients. Four anxieties for symptom, the normal side of lung, the effect after
      therapy and surgery. In thoracoscopic surgery on pneumothorax, to cut away just
      the bullous change does not mean to prevent the postoperative recurrence. Added
      treatments need beside resection of bullae because bullae often tend to
      regenerate near the suture line soon after thoracoscopic surgery. The covering
      method is the most effective in some added treatments. It is a method of covering
      regenerative oxidized cellulose mesh and fibrin glue on the suture line.
      Classification of air leakage level that was designed in Pneumothorax Research
      Center is clinically useful. This classification forms from level 1 to 4
      according to air leakage volume and pressure level. It is important to resolve
      the mechanism on postoperative regeneration of bullae at this point in order to
      ask for better surgery. Female pneumothorax and less than 15-year-old
      pneumothorax should be researched because they cause frequently postoperative
      recurrence.

PMID- 16910522
TI  - [Radical sublobar resection via hybrid video-assisted thoracic surgery (VATS) for
      small-sized non-small cell lung cancer].
AB  - Of late, small-sized lung cancers have become much more often found with the
      development of diagnostic image techniques. This article reviews the current
      status of radical sublobar resection such as segmentectomy and wide wedge
      resection for a peripheral clinical NO lung cancer tumor 2 cm or less in diameter
      in patients able to tolerate a lobectomy, with emphasis on its invasiveness as
      well as techniques and results. Several recent reports suggest that clinical
      results of sublobar resection in such highly selected patients is not worse than
      those of standard lobectomy. In addition to preservation of pulmonary function,
      this lung-saving surgery must provide a second chance to patients who have a
      higher risk of metachronous disease after surviving a first disease. Also, with
      the great interest in minimally invasive techniques for treating various
      pathologies, we have widely applied an integrated surgical approach that combines
      muscle-sparing minithoracotomy (incision, 4-8 cm) and video-assistance using
      mainly direct visualization of the lung resection, which we have called hybrid
      video-assisted thoracic surgery (VATS). The combination of sublobar resection and
      hybrid VATS might be an alternative as a much less invasive standard operation
      for patients with small peripheral lung cancers.

PMID- 16910523
TI  - [Video-assisted thoracoscopic debridement for acute empyema; a low invasive
      surgery for acute empyema].
AB  - BACKGROUND: Recent study reported that thoracoscopic surgery for acute empyema
      can achieve good results. We performed video-assisted thoracoscopic debridement
      (VD) in cases diagnosed as having acute empyema when conservative therapies such
      as administration of antibiotics or continuous thoracic drainage were not
      successful. METHODS: Two to 4 access ports were inserted into the empyema lumen,
      and surgery were conducted only under monitoring vision. After removing as much
      pus, coating, fibrin walls and peel as possible, a chest tube was set in the
      lumen for drainage. Thirty cases treated in our hospital were reviewed with
      respect to selected parameters. RESULTS: The interval from onset to surgical
      treatment was 41.0 +/- 21.0 days. All cases were considered in either
      fibrinopurulent phase or early organizing phase. Pathogenic bacteria were
      identified in 8 cases. Surgical duration was 93.1 +/- 26.6 minutes.
      Hospitalization period was 26.3 +/- 36.4 days. Twenty-seven cases showed
      improvement after the first VD procedure, while 3 cases required repeat
      procedures. CONCLUSIONS: VD may achieve good results not only in the
      fiburinopulurent phase but also in the early organization phase. VD is both low
      invasive and highly effective for acute empyema.

PMID- 16910524
TI  - [Minimally invasive surgery for primary hyperhidrosis].
AB  - Nine hundred twenty-three thoracoscopic sympathectomies for primary hyperhidrosis
      were performd in 462 patients (180 men, 282 women). Mean age was 29.2 (11-61)
      years. Synchronous bilateral sympathectomies were performed in 461 patient: right
      side alone in 1 patient. We started thoracic sympathectomy for primary
      hyperhidrosis under a thoracoscope using a 10 mm rigid endoscope in 1992. At
      present, we perform the surgery using a 3 mm rigid scope. The majority of our
      patient were satisfied with the result of operation. There is general agreement
      that postoperative side effect, such as compensatory and gustatory sweating, can
      cause discomfort and affect overall success. Thoracoscopic sympathectomy for
      primary hyperhidrosis is minimally invasive surgery and provides less pain and
      better cosmesis and short hospital stay, as compared with the conventional
      techniques. However, new technique is necessary to decrease compensatory sweating
      after the operation in the future and we should undergo a meticulous and critical
      selection to the patients in outpatient clinic.

PMID- 16910525
TI  - [Indication and procedure of video-assisted thoracoscopic surgery to thymic
      disease].
AB  - We retrospective reviewed minimally invasive video-assisted thoracoscopic surgery
      (VATS) to thymic diseases. These procedures were performed using intercostal and
      infrasternal approach with a sternum-elevator. Indications of this method are
      benign thymic lesions [mature teratoma, thymic cyst and myasthenia gravis (MG)]
      and small thymoma (non-invasive Masaoka stage I-II, less than 5 cm in diameter
      and nontouching to the left brachiocephalic vein). Fifty patients underwent VATS
      for 13 hemithymectomies (7 thymomas, 5 mature teratomas and 1 thymic cyst) and 37
      extended thymectomies (25 nonthymomatous MGs and 12 thymomatous MGs). Conversion
      to sternotomy was required in 3 cases of nonthymomatous MG because of bleeding
      from thymic vein in 1 case and pleural adhesion in 2 cases. Four cases of
      thymomatous MG were successfully treated with partial lung resection and/or small
      pericardial resection by VATS. New bipolar vessel sealing system (LigaSure V) is
      safer and more useful than metal clip and ultrasonic coagulator in VATS for
      thymic vein sealing, extraction of upper poles of thymus and incision of
      mediastinal pleura near phrenic nerve. VATS thymectomy should be useful from the
      standpoint of less invasive, less pain, rapid recovery, and good cosmetic
      results.

PMID- 16910526
TI  - [Minimally invasive surgery for mediastinal disease patients performed with
      special skills such as hand-assistance].
AB  - From 1997 to 2005, we performed endoscopic surgery on the thymus in 163 patients
      with myasthenia gravis or thymoma. The outcomes in these patients were analyzed,
      with the following conclusions obtained. Endoscopic extended thymectomy is
      acceptable as a standard operative procedure for myasthenia gravis patients.
      Endoscopic surgery on the thymus is indicated for stage II or less advanced cases
      of thymoma according to Masaoka classification. When hand-assisted thoracoscopic
      surgery (HATS) is used for surgery on the thymus, median sternotomy is not
      required. If applied only to cases in which it is truly indicated, endoscopic
      surgery on the thymus can be expected to shorten operative time compared with
      conventional operative procedures requiring median sternotomy and to serve as
      minimally invasive surgery in the true sense of the term.

PMID- 16910527
TI  - [Can video-assisted thoracoscopic surgery change the indication of lung resection
      for patients with lung cancer?].
AB  - Video-assisted thoracoscopic surgery (VATS) is associated with reduced pain,
      postoperative complications, release and responses of proinflammatory cytokines,
      and better ventilatory function during very early postoperative period after lung
      resection than standard thoracotomy. Because of the concern of local recurrence
      with pulmonary wedge resection by thoracotomy, anatomical lobectomy remains the
      curative procedure for lung cancer. However, same or better prognosis with a
      lesser resection by extended segmentectomy or wedge resection with VATS in
      patients with small lung cancer has been recently published. It suggests that
      these procedures would be applied for patients with poor pulmonary reserve who
      have not been considered as candidates for pulmonary resection.

PMID- 16910528
TI  - [Thoracoscopic surgery and postoperative respiratory complications].
AB  - In minimally invasive surgery in a thoracic surgery, thoracoscopic surgery
      already has been recognized as effective procedure for benign disease of the lung
      and the mediastinum. On the other hand, induction of thoracoscopic surgery to
      lung cancer surgical treatment raises various problems. We reviewed clinical
      outcome about 'low invasiveness and a postoperative respiratory complication of
      thoracoscopic surgery' mainly on surgical treatment for lung cancer. Furthermore,
      in recent years there is a problem of surgical treatment for lung cancer that we
      developed for emphysema, interstitial pneumonia with increase of elderly
      patients. As for stage IA patients who underwent a lobectomy with mediastinal
      lymphadenectomy, we reviewed what kind of influence on postoperative
      complications and long-term prognosis with the change of thoracotomy methods.

PMID- 16910529
TI  - [Endoscopic treatment for esophageal cancer].
AB  - Endoscopic therapy has now become the treatment of first choice of early
      esophageal cancer. We developed endoscopic esophageal mucosal resection (EEMR)
      tube method employing a silicon rubber tube. The 4-step EEMR-tube method is our
      standard way to resect a wide lesion. In the 1st step, the lesion containing the
      deepest area is mostly resected. In the 2nd step, the residual lesion is
      resected, repeating a similar procedure. In the 3rd step, the surrounding
      residual area is resected bythe double channel method. In the 4th step, resected
      edge and tiny residual portions are treated by hot biopsy and argon plasma
      coagulation. In the patients treated by endoscopic mucosal resection (EMR), local
      recurrence rate was 3.6% and most of these cases were treated successfully again
      by endoscopic maneuver.

PMID- 16910530
TI  - [Thoracoscopic approach for esophageal malignancies].
AB  - Current status and problems of thoracoscopic esophagectomy with mediastinal lymph
      node dissection for esophageal cancer are described. In the initial period at
      introduced this technique, many authors have concluded that postoperative
      morbidity after this procedure did not reduce compared with conventional
      technique. However, we clarified that this technique can be reduced the rate of
      postoperative pneumonia basis of series consisting a large number of experience,
      and conserve the respiratory function after surgery. Thoracoscopic approach for
      mediastinum can show the detailed anatomy and contribute to the improvement of
      safety of esophageal surgery. The establishment of a training system for this
      technique is important to achieve the standardization of thoracoscopic
      esophagectomy.

PMID- 16910531
TI  - [Endoscopic surgery for benign esophageal diseases].
AB  - Gastroesophageal reflux disease (GERD) and esophageal achalasia are common benign
      esophageal diseases. Today minimally invasive surgery is recommended to treat
      these diseases. Surgical indications for GERD are failure of medical management,
      medical complications attributable to a large hiatal hernia, 'atypical' symptoms
      (asthma, hoarseness, cough, chest pain, aspiration), etc. according to the
      Society of American Gastrointestinal Endoscopic Surgeons (SAGES) guidelines.
      Laparoscopic Nissen fundoplication has emerged as the most widely accepted
      procedure for GERD patients with normal esophageal motility. Partial
      fundoplication (e.g., Toupet fundoplication) is also considered to decrease the
      possibility of postoperative dysphagia. Although pneumatic dilatation has been
      the first line treatment for esophageal achalasia, laparoscopic Heller myotomy
      and partial fundoplication (e.g., Dor fundoplication) to prevent reflux is
      preferred by most gastroenterologists and surgeons as the primary treatment
      modality. Laparoscopic surgery for GERD and esophageal achalasia are effective in
      most patients and safe in all patients. Finally, laparoscopic surgery should be
      performed only by skilled surgeons.

PMID- 16910532
TI  - [Delusions of grandeur in patients with schizophrenia].

PMID- 16910533
TI  - [Nosological status of the intermediate area between schizophrenia and affective
      disorder].
AB  - Non-organic psychoses diagnosed with neither schizophrenia nor affective disorder
      are an aggregation of heterogeneous psychotic disorders including major groups
      such as acute polymorphic psychotic disorders and schizoaffective disorders.
      Historically, similar psychotic pictures have been reported in various cultures.
      However, their slightly different definition hindered comparative studies. Even
      after the establishment of an operational diagnostic guideline such as ICD-10,
      epidemiological studies on this intermediate area between schizophrenia and
      affective disorder have brought different findings, making the reliability of
      diagnosis of this area questionable. Moreover, the situation is further
      complicated that there exists not only cases which have repeated the same episode
      as the first, but also cases whereby the diagnosis has been changed to
      schizophrenia or affective disorder over a long-term course. K. Schneider, who
      suggested not differential diagnosis but differential typology in the area of
      endogenous psychoses, is right in thinking of the existence of this intermediate
      area. We should be satisfied with making a provisional diagnosis, should take a
      flexible attitude towards changes in diagnosis between episodes. And during
      diagnosis, we should not differentiate schizophrenia from affective disorders
      rigidly, nor define the intermediate area strictly.

PMID- 16910534
TI  - [Scientific status of psychopathology and its method of "understanding"].

PMID- 16910535
TI  - [Attempted suicide of youth with Asperger's disorder].
AB  - Research of Asperger's disorder is increasing through strong interest in this
      disorder. However, there are few reports on suicide attempts among youths with
      this disorder. We examined the clinical characteristics of serious suicide
      attempts of adolescents, and indicated the frequency of pervasive developmental
      disorders among them. In the present study, we reported a suicide attempt using
      briquettes by a youth with Asperger's disorder aged 23, who had a history of two
      suicide attempts by hanging. In this case, we examined the predisposing factors
      to suicide and possible intervention to prevent a re-attempt. As a result, in
      this case, we suggested that low self-esteem due to repeated serious social
      failures and feelings of isolation, although there was a social support system,
      were psycho-social predisposing factors. Moreover, the "conflict" between the
      patient and his parents, who should have provided social support for him, had
      made him feel alone. This "conflict" was composed of 1) the primary symptoms of
      Asperger's disorder (deficit of emotional reciprocity and unreasonable insistence
      on restricted thoughts.) and 2) his parents' insufficient comprehension of
      Asperger's disorder. This "conflict" was distinct from the conflict of
      interpersonal friction based on emotional interaction. In order to prevent a
      suicide re-attempt, we mainly intervened in the problem of low self-esteem due to
      repeated serious social failures and having feelings of isolation. We concluded
      that to prevent a suicide re-attempt in patients with Asperger's disorder, it is
      important to diagnose and treat the disorder and comorbidity, and it is more
      important to recognize and aggressively intervene in psycho-social predisposing
      factors.

PMID- 16910536
TI  - [How to withdraw from multi-high-dose drug therapy for schizophrenia].

PMID- 16910537
TI  - [Trends in multi-high-dose drug therapy for schizophrenia in Japan].

PMID- 16910538
TI  - [Psychobiological significance of antipsychotics in multi-high dose drug therapy
      for schizophrenia].
AB  - In this session, the development of antipsychotics and 'atypicality' were
      discussed firstly. Various concepts regarding 'atypicality' had the meaning of
      optimal modulation of dopamine. Then, the key role of dopamine for psychotic
      symptoms and the question how antipsychotics should work for managing those
      symptoms were treated by introducing the theories by Kapur and Yagi. And from all
      these reasons, it came to the conclusion that megadose-polypharmacy treatment
      should be avoided.

PMID- 16910539
TI  - [Theory in antipsychotic drug therapy for schizophrenia].
AB  - In Japan, antipsychotic polypharmacy with high doses for schizophrenia has been
      traditionally used. However, antipsychotic polyphamacy with high doses provide
      disadvantages for patient. Recent PET studies show that dopamine D2 occupancy
      with antipsychotics is important for the treatment of schizophrenia. First,
      antipsychotics become effective only at which their D2 occupancy exceeds 65%.
      Second, antipsychotics with D2 occupancy below 90% rarely causes occupancy
      exceeds 65%. Second, antipsychotics with D2 occupancy below 90% rarely causes
      extrapyramidal side effect. These results suggest that monopharmacy which uses a
      single antipsychotic agent with appropriate dose is recommended for schizophrenia
      treatment.

PMID- 16910540
TI  - [Necessity of novel single-antipsychotic-agent therapies for acute phase of
      schizophrenia].

PMID- 16910541
TI  - [Simplification and optimization in drug therapy for patients with schizophrenia-
      knowledge and techniques in drug switching].

PMID- 16910542
TI  - [Present status and future aspects of biological markers for diagnosis of mental
      disorders].

PMID- 16910543
TI  - [Molecular pharmacogenetic study on antipsychotic-drug therapy responders with
      depression or schizophrenia].

PMID- 16910544
TI  - [DNA microarray as a novel diagnostic marker for patients with depression].

PMID- 16910545
TI  - [Clinical availability of biological markers for diagnosis of schizophrenia:
      reactivity of frontal lobe function assessed with near-infrared spectroscopy].
AB  - Biological markers of psychiatric disorders can be employed both for research and
      clinical purposes, are classified into state, trait, and morbid markers, and are
      expected to be useful in diagnosis, treatment, and prediction of psychiatric
      disorders in clinical settings. Near-infrared spectroscopy that can measure
      reactivity of cerebral cortex function is one of biological markers for clinical
      purposes, and has revealed characteristic patterns of frontal lobe function in
      psychiatric disorders. Availability of biological makers for diagnosis of
      psychiatric disorders was examined by reviewing effect sizes of various
      biological markers in schizophrenia, showing that more elaborated markers for
      higher brain functions are promising: cognition (1.0-1.4), neurophysiology (0.8
      1.0), functional brain imaging (0.6-0.8), and structural brain imaging (0.5-0.6).

PMID- 16910546
TI  - [Morphological study on brains of patients with schizophrenia--its application to
      the objective diagnosis].

PMID- 16910547
TI  - [Eye movement in patients with schizophrenia].
AB  - To clarify the cognitive function of schizophrenia, the exploratory eye movement
      was investigated using S-shaped figures in patients with schizophrenia and their
      relatives. As a result, the exploratory eye movement has been found to be a
      biological marker that reflects a specific and trait factor of schizophrenia.
      Using the exploratory eye movement combined with brain functional imaging, the
      pathology of schizophrenia that the neural network centering on thalamus was
      damaged is being clarified. Moreover, the disease gene of schizophrenia may be
      discovered especially on the chromosome 22 using the exploratory eye movement as
      an endophenotype. In addition, the exploratory eye movement can be given as a
      powerful candidate of diagnostic tool for schizophrenia.

PMID- 16910548
TI  - [Psychosocial therapy].

PMID- 16910549
TI  - [History and development of cell-cell adhesion studies].

PMID- 16910550
TI  - [Structure and function of cadherin-catenin complex].

PMID- 16910551
TI  - [Regulation of cadherin activity].

PMID- 16910552
TI  - [Perspectives on structure elucidation of the cadherin-catenin complex].

PMID- 16910553
TI  - [Molecular mechanism behind the barrier function of tight junctions].

PMID- 16910554
TI  - [Loss of adhesive function of desmosomal cadherin and skin diseases in humans and
      animals].

PMID- 16910555
TI  - [Role of adhesion systems in inter-neuronal synapse formation].

PMID- 16910556
TI  - [Regulation of cell polarity in establishment of epithelium].

PMID- 16910557
TI  - [Role of nectins and nectin-like molecules in cell adhesion--a lesson on cell
      biology from the late Dr. Shoichiro Tsukita].

PMID- 16910558
TI  - [E-cadherin cell adhesion system in human cancer].

PMID- 16910559
TI  - [Control of junctional complex during cell adhesion remodeling].

PMID- 16910560
TI  - [Protocadherins: classification, structures and functions].

PMID- 16910561
TI  - [Molecular functions of seven-pass transmembrane cadherins--homophilic or
      heterophilic: that is the question].

PMID- 16910562
TI  - [Picture in clinical hematology].

PMID- 16910563
TI  - [The molecular mechanism of Notch-induced transformation and the therapeutic
      potential of its inhibitor].

PMID- 16910564
TI  - [Present status and future directions of clinical trial registration].

PMID- 16910565
TI  - [A multicenter clinical JCOG-LSG trial, from a protocol coordinator's
      standpoint].

PMID- 16910566
TI  - [Adult leukemia: current status of the clinical studies in Japan Adult Leukemia
      Study Group].

PMID- 16910567
TI  - [HLA serologically mismatched unrelated bone marrow transplantation].

PMID- 16910568
TI  - [HLA-haploidentical minitransplantation].

PMID- 16910569
TI  - [Reduced-intensity cord blood transplantation for adult hematological diseases].

PMID- 16910570
TI  - [Haploidentical 2- or 3-antigen-mismatched hematopoietic stem cell
      transplantation using in vivo Campath-1H].

PMID- 16910571
TI  - [Clinical significance of the "NIMA effect" in HLA-mismatched hematopoietic stem
      cell transplantation].

PMID- 16910572
TI  - [Review process of anticancer drugs in Japan].

PMID- 16910574
TI  - [Reduced-intensity stem cell transplantation using allogeneic peripheral blood
      stem cells from the same donor for relapsed leukemia after bone marrow
      transplantation].
AB  - We report the clinical courses of two cases with relapsed acute lymphoblastic
      leukemia (ALL) after allogeneic bone marrow transplantation (BMT). After
      reinduction chemotherapy, the patients received reduced-intensity stem cell
      transplantation using allogeneic peripheral blood stem cells harvested from their
      previous BMT donors. The conditioning regimen used consisted of fludarabine and
      melphalan. Graft-versus-host disease (GVHD) prophylaxis was performed with low
      dose cyclosporin A (CsA, 1 mg/kg/day d.i.v.) on its own. The regimen related
      toxicity was minimal, and stable engraftment was achieved. Since acute GVHD had
      not developed by day 30, CsA was stopped abruptly in both cases. After CsA
      withdrawal, acute GVHD developed, and subsequent chronic GVHD. One of two cases
      is alive without any relapse of the leukemia 40 months after the peripheral blood
      stem cell transplantation (PBSCT). In the other case, ALL relapsed 15 months
      after the PBSCT, however, complete remission was again induced concomitantly with
      reactivated GVHD. In both these cases, the results suggest that using PBSC as a
      stem cell source and abrupt cessation of GVHD prophylaxis provided a potent graft
      versus-leukemia effect.

PMID- 16910573
TI  - [De novo CD5-positive diffuse large B-cell lymphoma associated with autoimmune
      hemolytic anemia presenting as erythroid hypoplasia].
AB  - A 54-year-old woman was admitted due to high-grade fever, cervical
      lymphadenopathy and general malaise in May 2003. On examination, severe anemia
      was noted, direct Coombs and cold hemagglutinin tests were positive and the
      haptoglobin level was low in the peripheral blood. However, a bone marrow
      examination revealed marked erythroid hypoplasia. A diagnosis was made of co
      existing combined type autoimmune hemolytic anemia (AIHA) and erythroid
      hypoplasia. A pathologic diagnosis of de novo CD5-positive diffuse large B-cell
      lymphoma (de novo CD5+ DLBCL) was made based on a cervical lymph node biopsy. The
      patient was treated with CHOP accompanied by rituximab (R-CHOP), resulting in
      complete remission after 3 courses of chemotherapy. The AIHA and erythroid
      hypoplasia subsided after 2 courses of R-CHOP. The sera obtained during erythroid
      hypoplasia significantly inhibited the growth of erythroid progenitor cells
      (erythroid colony-forming units, CFU-E) from her bone marrow collected after
      recovery. We report here a patient with de novo CD5+ DLBCL associated with both
      AIHA and erythroid hypoplasia, suggesting that the lymphoma triggered an abnormal
      immunity which generated some humoral inhibitors against erythropoiesis.

PMID- 16910575
TI  - [Enteropathy-type T-cell lymphoma with CD8 and CD56 expression].
AB  - A 54-year-old male presented at a previous hospital with abdominal pain, where
      the patient was diagnosed as having abdominal and retroperitoneal
      lymphadenopathies by CT scan, then, he was referred to our hospital for further
      examination. Upper gastrointestinal endoscopy showed a tumor formation in the
      second portion of the duodenum, and there were medium sized atypical lymphocytes
      in biopsy specimens of the tumor. Since the atypical lymphocytes in the biopsy
      specimens were positive for CD3, CD8, CD56 and CD103 by immunostain, and had a
      rearrangement of the T-cell receptor 7-chain, the patient was diagnosed as having
      enteropathy-type T-cell lymphoma (ETL). Although ETL usually occurs as a
      complication of celiac disease, malabsorption and anti-gliadin antibodies, which
      are normally present in celiac disease, were not observed in this patient.

PMID- 16910576
TI  - [Pulmonary cryptococcosis occurring 6 months after cladribine therapy for
      relapsed follicular lymphoma].
AB  - We report a case of follicular lymphoma in which pulmonary cryptococcosis
      occurred with cladribine therapy. The case involved a 72-year-old man. He was
      diagnosed as having follicular lymphoma, grade 1, clinical stage IVA from a
      tongue tumor biopsy in January 2003. A total of 6 courses of R-CHOP therapy was
      performed, but no clear effect was found. A new cervical lesion appeared, so he
      was treated with a total of 2 courses of R-EPOCH therapy, and the effect was
      classed as stable disease. We started cladribine therapy (0.09 mg/kg, seven days
      of continuous infusion) from February 2004, and complete remission was achieved
      after 4 courses of cladribine therapy. In January 2005, an abnormal nodular
      shadow in the right S10 area was found on chest CT images which was diagnosed as
      pulmonary cryptococcosis by serum antigen and a trans-bronchial lung biopsy. We
      started fluconazole (200 mg a day, initially intravenous drip infusion, followed
      by oral intake), following which both the pulmonary shadow and serum antigen
      improved. Afterward, the fifth course of cladribine therapy and local radiation
      therapy were performed against a relapse of lymphoma, but cryptococcosis did not
      reappear. The prolonged bone marrow suppression after cladribine therapy was
      considered to be a severe adverse event. These findings suggest that it is very
      important to pay attention to any opportunistic infection such as pulmonary
      cryptococcosis.

PMID- 16910578
TI  - [Treatment of superficial carcinoma in the hypopharynx].
AB  - Superficial carcinoma of the esophagus is generally treated with endoscopic
      mucosal resection (EMR), yielding an acceptable prognosis and quality of life
      (QOL). With technical advances in endoscopy, it has become to possible to find
      superficial carcinoma even in the hypopharynx. Several reports suggest that such
      superficial carcinomas are treatable only with local mucosal resection. We
      treated 67 superficial carcinomas (49 cases) of the hypopharynx with local
      mucosal resection in our hospital, mainly with EMR. From 2004, we have resected
      11 lesions directly with endoscopic assist (endoscopic laryngo pharyngeal
      surgery; ELPS). With ELPS, it was very easy to recognize lugol-voiding lesions in
      the hypopharynx, and ELPS enabled us to do en bloc resection even for large
      lesions that could not be treated with EMR or with microscopic surgery. Eight of
      49 cases had transient side effects-2 vocal cord palsies, 2 vocal cord edemas
      with overnight intubation, 3 overnight intubations, and 1 pharyngitis. Six
      patients died of other diseases, and no metastasis or recurrence of superficial
      carcinoma was found. Diagnosis and treatment of superficial carcinoma of the
      hypopharynx may thus improve patient prognosis and QOL.

PMID- 16910577
TI  - [Deep vein thrombosis and pulmonary embolism in a patient with multiple myeloma
      treated with thalidomide and dexamethasone].
AB  - A 51-year-old man visited our hospital because of fever in 2003. With the
      discovery of the presence of a chest wall tumor, pleural effusion and M-protein,
      and increased plasma cells in the bone marrow, a diagnosis of multiple myeloma
      was established. Since the effect of combination chemotherapy followed by tandem
      auto-PBSCT lasted only one year, thalidomide and dexamethasone administration was
      started in November 2004. However, three months later, his lower limbs became
      swollen. Elevation of fibrin degradation product (FDP) and computed tomography
      findings suggested deep vein thrombosis and pulmonary embolism. With heparin and
      warfarin, these thromboses disappeared. Furthermore, chemotherapy strategies in
      addition to thalidomide were safely performed with anti-coagulation therapy. As
      thalidomide has become an accepted component in therapeutic strategies for
      multiple myeloma, careful attention must be paid to the prevention of thrombosis.

PMID- 16910579
TI  - [Clinical study on deep neck infection].
AB  - Deep neck infection (DNI) remains an emergent and life-threatening
      otolaryngologic disease. We examined 69 patients, 52 men and 17 women, with DNI,
      who were treated in our hospital between January 1995 and December 2004. The mean
      age of the patients with DNI was 50.0 years and the peak incidence was in the
      sixth decade. Twenty patients suffered from diabetes mellitus (DM). The primary
      DNI lesion was found in the tonsils in 34 cases, the oral cavity in 16 cases, and
      the pharynx in 12 cases, respectivelys. Among the 69 patients with DNI, the
      infection remained in the suprahyoid region in 31 cases, but it extended to the
      infrahyoid region in 33 cases and to the mediastinum in 5 cases. The titer of C
      reacting protein (CRP) and the duration of admission were considered as
      parameters of the severity of DNI. CRP was significantly higher in elderly
      patients, in patients with DM, and in patients whose infection extended to the
      infrahyoid region and to the mediastinum, however, significant difference was not
      found between men and women, or among the types of primary DNI lesions. Moreover,
      the duration of admission was significantly longer in elderly patients, in
      patients with DM, and in patients with infrahyoid and mediastinal DNI, whereas no
      significant differences were found between men and women or among the types of
      primary lesions. Therefore, age, DM, and the extension of DNI are considered to
      be important factors which determining the severity of DNI.

PMID- 16910580
TI  - [Effects of one-way speaking valve placement on swallowing physiology for
      tracheostomized patients: impact on laryngeal clearance].
AB  - Tracheostomy placement affects swallowing function, increasing the risk of
      aspiration. Recent studies suggest that because of increased risk of swallowing
      disturbance associated with tracheostomy, one-way speaking valve placement may
      help to reduce aspiration in tracheostomized patients. We hypothesize that
      airflow exhaled through the laryngeal cavity using the one-way speaking valve may
      improve the clearance of residual bolus from the upper airway, thus preventing
      bolus penetration and aspiration. We studied the effects of one way speaking
      valve placement on laryngeal clearance and swallowing physiology. Videoendoscopic
      and videofluoroscopic swallowing were examined in 16 patients with the
      tracheostomy, and swallowing was compared with and without the one-way speaking
      valve in place. Valve Valve placement significantly improved laryngeal clearance
      and the incidence of penetration during swallowing. placement did not, however,
      significantly affect pharyngeal bolus residue, laryngeal elevation, pharyngeal
      delay or aspiration. Factors associated with the resumption of oral feedings were
      sufficient laryngeal elevation during swallow and the prevention of laryngeal
      penetration and aspiration. We concluded that one-way speaking valve placement
      improves laryngeal clearance and prevents laryngeal penetration, resulting in
      better oropharyngeal swallowing physiology and oral feeding.

PMID- 16910581
TI  - [Delayed facial nerve palsy after otologic surgery].
AB  - Delayed facial nerve palsy (DFP) is rarely experienced after otologic surgeries
      that do not directly touch the facial nerves, such as tympano-mastoidectomy,
      cochlear implants, and stapes surgery, and is troublesome to both surgeons and
      patients if it happens. Here, we report 7 cases of DFP, including one case that
      developed DFP after endolymphatic sac surgery. The ratios of occurrence were as
      follows: 0.7% (2/305) for tympano-mastoidectomy, 0.8% (3/354) for cochlear
      implant, 0.4% (1/260) for stapes surgery and 1.0% (1/98) for endolymphatic sac
      surgery. All otologic surgeries, except for endolymphatic sac surgery, exposed
      the chorda tympani, and all surgeries, except for stapes surgery, underwent
      drilling for a mastoidectomy. Furthermore, DFP was always observed ipsilaterally
      to the operated ear after otologic surgeries and was never seen after benign
      parotid tumor surgery or total laryngectomy. Therefore, there may be a strong
      relationship between DFP and the procedures, used during otologic surgeries.

PMID- 16910582
TI  - Bisphosphonate and low-dose dexamethasone treatment for patients with hormone
      refractory prostate cancer.
AB  - We evaluated the effects of bisphosphonate (BP) treatment in five patients with
      hormone-refractory prostate cancer (HRPC), experiencing bone pain from metastases
      to the bone, and assessed changes in serum prostate specific antigen (PSA)
      levels, bone pain, and quality of life (QOL). Treatment with incadronate disodium
      (10 mg) in saline was administered at 2-week intervals for a total of 6 times.
      Evaluation of the treatment included the incidence of adverse events, QOL, bone
      pain, pain scale, and blood analyses including tumor markers. BP treatment was
      generally well tolerated by all five patients. The effects of BP treatment on
      serum PSA values were evaluated as prominent response (PR), no change (NC) and
      progressive disease (PD) in one, two and two cases of PD, respectively. During BP
      treatment, serum type I procollagen values decreased in patients, but there was
      no large change in serum type I collagen values. Only one patient experienced
      increased pain; pain was well controlled in the others. The QOL evaluation by
      Short-Form 36 (SF-36), showed no change in scores during BP treatment except for
      general health. These results suggested that BP treatment is safe and feasible.
      It may be effective for the treatment of those HRPC patients with bone pain and
      may become one of the choices for treatment of HRPC.

PMID- 16910583
TI  - [Clinical course of patients with negative initial prostate biopsy].
AB  - Of 227 men with a negative initial biopsy, the clinical course of 99 men who
      could be regularly followed using prostate specific antigen (PSA) determination
      was retrospectively analyzed. A repeat biopsy was recommended if the men showed
      persistent elevation of PSA > 10 ng/ml, PSA velocity (PSAV) > 0.75 ng/ml/year, or
      persistent abnormality on digital rectal examination and/or transrectal
      ultrasonography. A repeat biopsy was performed on 43 men. Because of the
      indication for a repeat biopsy, the PSAV of the 43 men who received a repeat
      biopsy was higher than that of the 56 men who did not. Clinically organ-confined
      cancer was detected in 18 patients (detection rate 41.9%). The patients having
      cancer had a higher PSAV (median 1.950) than those without the disease (median
      0.900). Of 19 men aged 75 years and older at the initial biopsy, a repeat biopsy
      revealed organ-confined cancers in 4 out of 10 men. During follow-up of the 19
      elderly men, 11 developed co-morbid illnesses such as cerebral infarction,
      ischemic heart diseases and other malignancies, and 4 died of the diseases. Thus,
      PSAV seems to be the best parameter for a repeat biopsy. Elderly men may not
      benefit from a repeat biopsy because they are unlikely to have lethal prostate
      cancer and highly likely to develop co-morbid illness that would affect their
      life-span.

PMID- 16910584
TI  - Recovery of serum prostate specific antigen value after interruption of
      antiandrogen therapy with allylestrenol for benign prostatic hyperplasia.
AB  - Decrease in serum prostate specific antigen (PSA) concentration is inevitably
      associated with antiandrogen therapy for benign prostatic hyperplasia (BPH), and
      might mask the presence of prostate cancer or delay its diagnosis. To determine
      the appropriate timepoint for determination of correct PSA value, we sequentially
      measured serum PSA and testosterone levels after discontinuation of antiandrogen
      therapy for BPH. With informed consent, 12 patients (72.8 +/- 12.2* years old)
      with BPH were treated with allylestrenol 50 mg/day for 4 months. Serum
      testosterone and PSA concentrations were determined before and just after
      treatment, as well as every month after treatment up to 3 months. After treatment
      with allylestrenol for 4 months, mean serum testosterone and PSA levels were
      significantly decreased from 408 +/- 136* to 87.9 +/- 76.2* ng/dl, and from 2.81
      +/- 0.87* to 2.04 +/- 0.82* ng/ml, respectively. The mean serum PSA level
      recovered to the pretreatment level within 2 months and mean serum testosterone
      concentration within one month after discontinuation of administration. In
      conclusion, during treatment of BPH with antiandrogen allylestrenol, a two-month
      washout is adequate for determination of correct PSA value (*: M +/- SD).

PMID- 16910585
TI  - Clinical study for management of supportive treatment for high-dose chemotherapy
      with peripheral blood stem cell transplantation (PBSCT) for intractable
      testicular tumor.
AB  - The side effects of high-dose anti-cancer drug chemotherapy with peripheral blood
      stem cell transplantation (PBCST) for the treatment of intractable testicular
      tumor are very serious. In particular, agranulocytosis in bone marrow suppression
      may be life threatening. In this study, we examined opportunistic infectious
      diseases and preventive counter measures in the compromised conditions of anti
      cancer drug chemotherapy. The patients underwent anti-cancer drug chemotherapy
      with PBCST for the treatment of intractable testicular tumors at Kobe University
      Hospital from September 1996 to September 2002. The high-dose chemotherapy
      regimen consisted of total doses per course of 1,250 mg/m2 carboplatin, 1,500
      mg/m2 etoposide, and 7,500 mg/m2 ifosfamide. Twenty-four men (median age, 30
      years; range, 18-70 years) received 50 courses of chemotherapy in total. The
      nadir of peripheral leukocyte counts was less than 1,000/mm3 in all courses, and
      the mean period was for 7.1 days. None of these patients developed critical
      sepsis leading to disseminated intravascular coagulation or treatment-related
      death. Our detailed data show that we can perform high-dose anti-cancer drug
      chemotherapy with PBSCT for intractable testicular tumors without serious
      infectious complications if we take sufficient preventive countermeasures for
      infectious diseases.

PMID- 16910586
TI  - [Comparison and outcome of prevalence of concurrent diseases in patients with
      urological malignant diseases].
AB  - We compared the prevalence of concurrent diseases (diabetes mellitus,
      hypertension, ischemic heart diseases and apoplexy) in patients with renal cell
      carcinoma, bladder carcinoma and prostatic carcinoma diagnosed in our department
      with that in all patients in our department analyzed using Mantel-Haenszel
      regression. In hypertension, there was a significantly high prevalence of
      patients with renal cell carcinoma (p < 0.05) in males and females, and prostatic
      carcinoma (p < 0.05). In diabetis mellitus, ischemic heart diseases and apoplexy,
      no apparent characteristic of prevalence was recognized. The close relationship
      between renal cell carcinoma, prostatic carcinoma and hypertension in this study
      corresponded with previous reports.

PMID- 16910587
TI  - The efficiency of Sairei-to for retroperitoneal fibrosis: two case reports.
AB  - The conventional approach for management of retroperitoneal fibrosis (RF), an
      inflammatory process of retroperitoneal fibro-adipose tissue, leading to the
      compression and obstruction of the ureters and other adjacent organs is
      ureterolysis with omental wrapping, and an effective alternative to surgery is
      immunosupressive medication such as oral corticosteroids. Sairei-to (TJ-114) is a
      traditional herbal medicine used for the treatment of RF in Japan. It has both
      anti-inflammatory and anti-allergic effects. Here we report two cases of RF
      successfully treated with Sairei-to. One case was idiopathic and the other was
      caused by artificial graft-induced vasculitis. Both cases were treated with
      Sairei-to following the decompression of uremia by precutaneous nephrostomy or
      indwelling ureteral stents. There was hardly any ureteral obstruction three
      months after the administration of Sairei-to. They have been doing well for 12
      and 26 months. Sairei-to rarely causes side effects such as immunodeficiency,
      gastro-duodenal ulcer and osteoporosis that often accompany long-term
      administration of corticosteroids. Sairei-to is a safe and effective medicine for
      the treatment of RF. We therefore recommend Sairei-to as an alternative for
      corticosteroid therapy.

PMID- 16910588
TI  - [A case of cystic ganglioneuroma of adrenal gland presenting as a huge
      retroperitoneal mass].
AB  - A 35-year-old man presented with a 17-month history of abdominal distension and
      left upper quadrant pain. He had no episodes suggesting the presence of
      hypertension. Hormonal studies were insignificant. Imaging studies demonstrated a
      bulky tumor with cyst formation measuring 22 cm. Preoperative differential
      diagnoses included an adrenal tumor, extra-adrenal retroperitoneal tumor and
      pancreatic mucinous tumor. Intraoperatively, no abnormality was observed in the
      pancreas. A tight adhesion of the tumor to the left kidney necessitated an en
      bloc resection of the tumor with the left kidney. The resected specimen, 22 x 20
      x 8 cm, weighed 5,050 g. Pathologically, the tumor was ganglioneuroma originating
      from the left adrenal gland. Convalescence was uneventful, and abdominal symptoms
      disappeared. The patient has been doing well without evidence of recurrece 48
      months after the operation.

PMID- 16910589
TI  - [Living unrelated renal transplantation in an eldery couple: a case report].
AB  - We present a 60-year-old female who underwent living unrelated renal
      transplantation from her 62-year-old husband. The primary immunosuppression
      consisted of tacrolimus, mycophenolate mofetil and steroid. We did not recognize
      any rejection in a histopathological study. The total ischemic time to carry out
      anastomosis of the two renal arteries was 121 minutes. After hemodialysis 5 times
      for acute tubular necrosis, her renal function improved. She was discharged on
      the 33rd postoperative day when her serum cretinine level was 1.0 mg/dl. The
      graft function was stable at 6 months after transplantation. We discussed living
      unrelated renal transplantation in the elderly population in Japan.

PMID- 16910590
TI  - [A case of pheochromocytoma associated with incidental multiple renal cell
      carcinoma originating from acquired cystic disease of the kidney in
      hemodialysis].
AB  - The patient was a 52-year-old woman maintained on peritoneal dialysis for 9 years
      and on hemodialysis for 7 years. This patient complained of palpitations and
      hypertensive attack during the hemodialysis. Computed tomography and magnetic
      resonance imaging demonstrated the presence of right adrenal tumor(1.5 x 1.5 cm)
      and bilateral multiple renal cysts. Right adrenal pheochromocytoma was confirmed
      by elevated serum level of catecholamines and diagnosed by 131I-MIBG scintigram.
      This patient underwent right adrenalectomy and nephrectomy in consideration of
      future generation of cancer in the acquired cystic kidney. Histological
      examination confirmed malignant pheochromocytoma and small multiple renal cell
      carcinomas. The patient was alive without any recurrence 6 months
      postoperatively. To our knowledge, this is the fifth case of adrenal
      pheochromocytoma and renal cell carcinoma associated ACDK in a hemodialysis
      patient in the Japanese literature.

PMID- 16910591
TI  - [Temporary inferior vena cava filter applied to 4 patients with urological
      disease].
AB  - A temporary inferior vena cava (IVC) filter was placed in 4 patients. Patient 1
      had an advanced testicular germ cell tumor with IVC tumor thrombosis, patient 2
      presented with a large adrenal tumor with IVC tumor thrombosis, patient 3 was
      found to have deep vein thrombosis following grade 3b renal injury, and patient 4
      was suffering severe SLE with renal vein thrombosis. The temporary inferior vena
      cava filter prevented pulmonary thromboembolism in all cases, and no adverse
      reaction was observed. Temporary inferior vena cava filter is safe and useful to
      prevent pulmonary thromboembolism associated with urological disorders.

PMID- 16910592
TI  - [Ureteral tumor occurring from remaining stump: a case report].
AB  - Primary tumor originated from ureteral stump following nephrectomy for benign
      disease is extremely rare. A 79-year-old male was referred to our department for
      asymptomatic macroscopic hematuria. He had undergone left simple nephrectomy for
      renal tuberculosis 52 years ago. Cystoscopic examination revealed a ureteral
      tumor on the residual ureteral orifice. Under the diagnosis of left ureteral
      stump tumor, which was subsequently enhanced on computer tomographic scan and
      magnetic resonance imaging, he received partial cystectomy and excision of the
      left ureteral stump. The histological examination revealed grade 2 to 3
      urothelial carcinoma with muscle invasion (pT2). He received no adjuvant
      chemotherapy. He is now alive and free from recurrence 2 months post-operatively.
      This is the 21st case reported in the Japanese literature.

PMID- 16910593
TI  - Annular rectal constriction due to infiltration by bladder cancer.
AB  - Invasive bladder cancers frequently show lymphatic or hematogenous metastasis.
      Furthermore, aggressive local invasion into adjacent structures is also commonly
      observed. However, the occurrence of rectal stricture due to infiltration by
      bladder cancer is relatively rare. Here, we report three patients with aggressive
      bladder cancer causing rectal obstruction.

PMID- 16910594
TI  - [The diagnosis and treatment for carcinoma in situ of the bilateral upper urinary
      tracts after total cystectomy and ileal conduit by intentionally inducing
      hydronephrosis].
AB  - We report the diagnosis and treatment for carcinoma in situ of the bilateral
      upper urinary tracts after total cystectomy and ileal conduit by intentionally
      inducing hydronephrosis. A 75-year-old man whose chief complaints were
      macroscopic hematuria and bladder irritabilities was diagnosed carcinoma in situ
      of the bladder and underwent total cystectomy and ileal conduit. 26 months after
      the operation, the cytological examination of ileal conduit urine revealed
      urothelial carcinoma. Since the radiographic findings in the upper urinary tracts
      and ileal conduit were negative, we constructed bilateral percutaneous
      nephrostomies by intentionally inducing hydronephrosis. Since two serial
      cytological examinations of the urine sampling from the bilateral pyeloureteral
      systems revealed urothelial carcinoma, we performed the percutaneous Bacillus
      Calmatte-Guerin perfusion of the bilateral upper urinary tracts. The therapy was
      repeated at weekly intervals for a total of 11 perfusions and the cytological
      examination of ileal conduit urine became negative 4 months after the beginning
      of the therapy. Intentionally induced hydronephrosis is useful for the diagnosis
      and treatment for carcinoma in situ of the bilateral upper urinary tracts after
      total cystectomy and ileal conduit.

PMID- 16910595
TI  - Unsuspected pheochromocytoma of the urinary bladder in an 81-year-old woman.
AB  - The clinical feature of bladder pheochromocytoma is usually typical, but the
      diagnosis is occasionally delayed because of the rarity of this neoplasm. The
      oldest patient previously reported is 78 years old. In this report, we present an
      81-year-old woman with unsuspected bladder pheochromocytoma.

PMID- 16910596
TI  - [Local recurrence of spermatic cord liposarcoma: a case report].
AB  - A 46-year-old man had undergone radical high orchiectomy because of a tumor of
      the right spermatic cord. Pathological diagnosis was atypical lipomatous tumor.
      Six years later, he had asymptomatic swelling in his right groin. Local
      recurrence was suspected, and surgical resection of the tumor with a sufficient
      surgical margin was performed. Pathological diagnosis was well-differentiated
      liposarcoma, sclerosing type. Ten cases of recurrent spermatic cord liposarcoma,
      including the present case, have been reported in Japan. Because of the
      possibility of local recurrence, spermatic cord liposarcoma needs strict and long
      term follow up.

PMID- 16910597
TI  - [Tuberculosis complicated with liver cirrhosis].
AB  - OBJECTIVES: The aim of this study is to examine the clinical characteristics of
      tuberculous patients complicated with liver cirrhosis. MATERIALS AND METHODS: 44
      patients (39 males and 5 females) admitted to Tokyo National Hospital since 1991
      till 2005 were analysed. RESULTS: Eighteen patients died and liver failure was
      the leading cause of death (N = 10). Hepatitis C viral infection (N = 17), and
      excessive alcohol consumption (N = 13) were the major causes of liver cirrhosis.
      Twenty five patients followed-up for more than 3 months were further selected for
      the detailed analyses. Multi-drug combination chemotherapy including isoniazid,
      rifampicin and ethambutol was administered in 22 patients. Adverse effects were
      seen in 20 patients. The numbers of patients with leukopenia, thrombocytopenia
      and hyperbilirubinemia were 10, 9 and 3, respectively. They recovered following
      the alteration of chemotherapeutic regimen or drug desensitization. CONCLUSION:
      Tuberculous patients with liver cirrhosis are characterized with higher mortality
      rate and higher frequency of adverse effects of antituberculous chemotherapy.
      Multi-drug combination regimen could be tolerable under adequate surveillance of
      side effects even in the situation of preexisting liver dysfunction.

PMID- 16910598
TI  - Decentralized DOTS shortens delay to TB treatment significantly in Cambodia.
AB  - SETTING: Rural districts in Cambodia with and without decentralized health center
      based DOTS program. OBJECTIVE: To compare delays to treatment and behavior of
      patients up to diagnosis, between the pilot districts where DOTS is decentralized
      through the health centers, and the control districts where DOTS is provided
      through hospitals. DESIGN: A cross sectional study with structured questionnaire
      interviews to all new smear-positive TB patients aged 15 years or older who were
      registered in the study sites from May 1st to July 31st in 2002. RESULTS: The
      total delay in the pilot districts was significantly shorter than that in the
      control districts (median 58 days vs. 232 days, p < 0.01). The median doctors'
      delay within TB service in the pilot districts was 10 days and that in the
      control was 6 days. The period between first consultation to any health care
      provider and first visit to a TB service center, subsequent contact delay, was
      longer than any other type of delay and significantly different (24 days in pilot
      vs. 185 days in control, p < 0.01). The distance and travel costs to a TB service
      center were the factors associated with delay in seeking diagnosis of
      tuberculosis. No other variables had any significant association with the delay.
      CONCLUSION: Decentralizing DOTS to primary care health centers is highly
      effective in reducing the delay to TB treatment in Cambodia.

PMID- 16910599
TI  - [Detection of rpoB mutations in rifampicin-resistant Mycobacterium kansasii].
AB  - PURPOSE: To detect rifampicin-resistant mutations in Mycobacterium kansasii (M.
      kansasii). METHODS: We examined the M. kansasii isolates from sputum of patients
      at National Hospital Organization Kinki-chuo Chest Medical Center from January 1,
      2001 to November 30, 2005 using drug-susceptibility testing, and analyzed 69-bp
      fragment of rpoB gene in rifampicin-resistant strains. RESULTS: Three strains
      from 314 isolates were determined as rifampicin resistant using drug
      susceptibility testing. Those strains showed a rise in minimum inhibitory
      concentration (MIC), and had the mutations in rpoB gene. These point mutations in
      codons 513 and 516 were common mutations found in rifampicin-resistant clinical
      isolates of M. tuberculosis. DISCUSSION: We verified the association between rpoB
      gene mutations and rifampicin resistance in M. kansasii.

PMID- 16910600
TI  - [Geospatial analysis of tuberculosis in Tokyo].
AB  - PURPOSE: To assess geographic variations in the incidence of tuberculosis in
      Tokyo. METHODS: Using information on tuberculosis incidence, 2000 to 2002, from
      the annual notification report, patients were categorized into 8 groups by sex
      and age. We then calculated the Standardized Incidence Ratio (SIR) for each of
      the 23 wards in Tokyo. The SIR map was described by spatial interpolation and
      evaluated by cross validation. Spatial scan statistics were used to detect the
      significance of high-risk areas across the region. We compare this with the
      proportional distribution of those receiving public assistance and according to
      the SIR. RESULTS: The geographic variations of SIR did not show a uniform pattern
      for each group. Spatial scan statistics clearly identified locations, that were
      significantly high for male groups over 20 years old. Groups under 20 years old
      and all female groups did not produce high incidence cluster, which are likely to
      demonstrate spatial features of the proportion of those receiving public
      assistance. CONCLUSIONS: The geographic distribution of the proportion of those
      receiving public assistance should impact upon the geographic distribution of the
      high incidence clusters. However, considering the results of the young age group
      and each female group, we suggest that recent infection risk among local
      habitants was almost uniform, with a slightly higher tendency in urban locations
      of Tokyo.

PMID- 16910601
TI  - [Tsukamurella tyrosinosolvens cultured from sputum of a patient who received
      total gastrectomy for gastric cancer].
AB  - A 79-year old woman underwent total gastrectomy under the diagnosis of gastric
      cancer in Feb. 2003. In the beginning of Jan. 2005, she noticed hemosputum and
      was admitted to our hospital. Chest radiograph and CT disclosed bilateral upper
      lobe-dominant nodular opacities in the subpleural areas and ground-glass
      opacities in right S6. Transbronchial lung biopsy was performed, but no useful
      information for the diagnosis was obtained. Ziehl-Neelsen stain was negative for
      the smear of the sputum at admission, but weakly stained acid-fast bacilli were
      grown in the MGIT culture. By the analysis of mycolic acid and menaquinone of the
      cell membrane, the bacilli were identified as Tsukamurella. Since she was
      asymptomatic and repeated sputum examination revealed negative bacilli, she has
      been observed at the outpatient clinic without any treatment.

PMID- 16910602
TI  - [Clinicoradiological diagnosis of respiratory infections: estimate of pathogens
      by radiological findings and the strategy for treatment].
AB  - This review discusses the clinicoradiological findings of pulmonary tuberculosis
      as well as non-tuberculous mycobacteria. To make a differential diagnosis between
      pneumonia and mycobacterial infections, it is very important to analyze the
      radiological findings of inflammatory lung diseases based on normal anatomical
      structures. If clinicoradiological analyses could make these differentiations,
      the appropriate treatment strategy for respiratory infections could be
      established. To accomplish this, exact orientations of pulmonary lobulus, acinus,
      and respiratory bronchioles is very important. Then, through analyzing chest CT
      findings and distribution patterns based on normal anatomical structures.
      estimation of causative pathogens could be possible. To differentiate infections
      caused by Mycobacterium tuberculosis from non-tuberculous mycobacteria, several
      important criteria have been demonstrated. Briefly, in MAC respiratory infection,
      right middle lobe and left lingula are frequently involved and centrilobular
      nodules and diffuse bronchiectases are characteristic radiological findings.

PMID- 16910603
TI  - [Ganglion cyst of the shoulder: six cases and review of the literature].
AB  - Paraglenoid glenohumeral cysts can be observed in 2-4% of the general population,
      particularly in men during the third and fourth decade. On average, these cysts
      measure 10-20 mm in diameter and are located preferentially on the
      posterosuperior aspect of the glenoid. An articular origin (rim injury) is
      generally accepted. The pathogenesis is similar to that of meniscal cysts.
      Depending on the exact localization, there is generally little clinical
      expression. The most frequent complication involves compression of the
      suprascapular nerve leading to suffering of the supra and/or infraspinatus.
      Amyotrophy can occur without clinical expression. An attentive examination is
      necessary to identify the cyst. EMG is often falsely negative. MRI is currently
      gold standard diagnostic tool but will probably be improved with arthro-MRI.
      Ultrasonography and computed tomography can visualize with difficulty small cysts
      located very close to the bone. The best treatment is arthroscopy which enables
      complete cure (emptying the cyst and resection or suture of the rim). We present
      a review of the pertinent literature together with a retrospective series of six
      cases of paraglenoid glenohumeral ganglion cysts.

PMID- 16910604
TI  - [Arthro-C-scan analysis of rotator cuff tears healing after arthroscopic repair:
      analysis of predictive factors in a consecutive series of 167 arthroscopic
      repairs].
AB  - PURPOSE OF THE STUDY: Arthroscopic repair of rotator cuff tears is a well
      described technique with good clinical results. The purpose of this work was to
      use the arthro-CT-scan to evaluate tendon healing after arthroscopic repair and
      search for epidemiological, anatomic and technical factors predictive of tendon
      healing. MATERIAL AND METHOD: This prospective consecutive series included 167
      non-randomized shoulders. All patients underwent a preoperative assessment using
      the crude Constant score and a standard x-ray protocol to evaluate cuff status.
      Cuff repairs were all performed arthroscopically. The crude Constant score was
      used to follow patients. A control arthroscan was obtained in 148 patients.
      RESULTS: Mean patient age was 59 years, 46% men and 77% dominant side. Mean
      duration of symptoms before repair was nine months. The tears resulted from
      trauma in 28%, including 9% occupational accidents. The preoperative mean crude
      Constant score was 52.4 (range 15-77). An isolated tear of the supraspinatus was
      observed in 68%. Frontal retraction of the supraspinatus was distal in 74%. In 29
      cases, reduction was difficult. The quality of the tendon was considered normal
      in 56 cases and non-anatomic repair was necessary in six. At last follow-up (19
      months on average) the mean crude Constant score was 80 (range 49-95). Arthro-CT
      scan was performed to control healing in 148 patients and revealed anatomic
      healing in 69, defective healing in 27, and repeated tears in 52 shoulders.
      Factors predictive of healing were: tear less than six months old, sedentary
      occupational activity, non-dominant side, young patient, female gender, isolated
      small non-retracted tear of the supraspinatus, normal appearance of an easily
      reduced tendon, and good bone quality. DISCUSSION: Time from tear to repair was
      long in this series. Tendon and muscle changes occurring after the injury could
      explain in part the healing failures. CONCLUSION: But this study confirmed good
      functional and anatomic results given by arthroscopic repair of rotator cuff
      tears.

PMID- 16910605
TI  - [Bone and soft tissue loss of the proximal interphalangeal joint of the long
      fingers: emergency treatment with a Swanson implant: prospective study of ten
      patients with mean 2.7 year follow-up].
AB  - PURPOSE OF THE STUDY: Injury of the proximal interphalangeal joint (PIP) with
      loss of bone and soft tissue (joint surface, tendon, skin cover) can compromise
      finger vascularization. Fusion or amputation is often proposed. We report our
      experience with another solution, emergency implantation of the Swanson implant.
      MATERIAL AND METHODS: Thirteen patients, mean age 47.4 years (range 18-76)
      underwent emergency surgery between 1997 and 2003. In twelve patients, the finger
      injury occurred when working with wood. For ten of the thirteen patients, the
      injury occurred during recreational activity. The index was involved when only
      one ray was injured. The thumb was spared in all patients. Joint tissue was lost
      in all patients. The head of P1 was injured in all cases creating a situation
      incompatible with fusion without loss of finger length. All patients underwent an
      emergency surgery for complete reconstruction of the PIP joint with Swanson
      implant, tendon reconstruction or suture, and skin cover performed during the
      same procedure. RESULTS: Ten patients, 16 implants, were reviewed at mean 2.7
      years (range 1-6 years). Mean flexion reached 41.8 degrees (range 20-80 degrees).
      Maximal amplitude of flexion was achieved at one year and remained unchanged
      thereafter. There were no cases of infection, or secondary amputation. Two
      implant fractures were noted with no functional impact at six years. There were
      four cases of instability. DISCUSSION: Most reports in the literature concern
      composite blast or firearm injuries. Ours appears to be the first series
      involving injuries occurring while working with wood. Most of the lesions caused
      by the circular saw were tangential, damaging the dorsal aspect of several PIP
      joints. Classically, it would be logical to propose arthrodesis if the bone and
      cartilage loss is not excessive, but with the loss of joint motion provided by
      implants. Like Nagle, we propose emergency implantation of a Swanson prosthesis
      if soft tissue and tendon reconstruction can be achieved, avoiding amputation.
      Although the technique is relatively simple, implantation of a Swanson prosthesis
      implies certain prerequisites, particularly ligament repair and correct
      alignment. Oversized implants appear to be better. We did not have to perform any
      secondary arthrodesis.

PMID- 16910606
TI  - [Total knee arthroplasty for recent severe fracture of the proximal tibial
      epiphysis in the elderly subject].
AB  - PURPOSE OF THE STUDY: Bone comminution, serious cartilage damage, and the poor
      mechanical quality of osteoporotic bone create a difficult challenge for
      osteosynthesis of joint fractures in the elderly subject. Poor results with
      certain hip, elbow and shoulder fractures have lead certain authors to propose
      emergency arthroplasty in selected cases. We report our experience with four knee
      arthroplasties implanted for recent severe fracture of the proximal tibial
      epiphysis in elderly subjects. MATERIAL AND METHODS: Four independent patients
      aged over 75 years presented a severe comminutive fracture of the proximal
      epiphysis of the tibia (Three Schatzker 5, one Schatzker 4). After obtaining the
      patients' informed consent, early knee arthroplasty was performed. A long-stem
      cemented tibial piece was used on which the epiphysis was reconstructed. Implants
      providing support for ligament deficits were used in all cases. Immediate weight
      bearing was authorized. RESULTS: Follow-up ranged from two to seven years. The
      IKS function score (15, 60, 100, 100) depended on the patient's general status.
      The IKS knee score was excellent for three knees (90, 95, 95), and fair in one
      (45). Re-operations were not needed in any of the patients. All x-rays showed
      bone healing with correctly aligned limbs (less than 2 degrees deformation).
      There were no lucent lines at last follow-up. DISCUSSION: Early arthroplasty for
      complex fractures of the proximal epiphysis of the tibia is a realistic option.
      Using a cemented long-stem tibial piece ensures primary stability sufficient for
      early weight-bearing before bone healing. Use of a constrained prosthesis, or
      better a hinged prosthesis, can be questioned but avoids the difficulty of
      ligament balance on an osteoporotic knee with a destroyed joint surface. None of
      the patients required reoperation and the results in terms of pain were
      excellent. The overall outcome depends on the general status of the patient.

PMID- 16910607
TI  - [Accuracy of total knee replacement bone cuts using a conventional ancillary
      system: 300 Innex total knee arthroplasties].
AB  - PURPOSE OF THE STUDY: Short-term functional results and long-term outcome in
      terms of stability and wear greatly depend on the precision of the bone cuts. We
      wanted to know whether conventional ancillaries are still competitive in terms of
      accuracy in comparison with computer-assisted navigation systems. A few
      comparative studies favor navigation, but have generally only included a small
      number of patients. We studied radiographically a prospective consecutive series
      of 300 total knee prostheses (Innex, Zimmer) implanted with the conventional
      technique by the same operator. MATERIAL AND METHODS: A telegonometric view in
      the upright position and a short lateral view were obtained in all patients. In
      the AP view, implants were measured in comparison with the mechanical axis of the
      femur (F) and the tibia (T). On the lateral view, the prosthesis-tibial shaft
      angle (PT) was measured from the proximal portion of the tibial shaft and the
      prosthesis-femoral shaft angle (PF) from the distal portion of the femur. The
      same operator made all measurements using the same optimal conditions. The series
      included 178 women and 122 men, mean age 72 +/- 8 years who presented genu varum
      (n = 248 knees) and genu valgum (n = 52 knees): degenerative disease (n = 238),
      polyarthritis (n = 4), hemophilic arthropathy (n = 3), necrosis (n = 3), revision
      of unicompartmental prosthesis (n = 8), and osteotomy (n = 44). RESULTS: The
      standard x-ray protocol was performed at two months in all patients. The
      mechanical axis (HKA) was 179.4 +/- 2.4 degrees (range 173-186 degrees) and was
      +/- 3 degrees in 87% of knees with no difference for varum and valgum. F was 90.1
      +/- 1.4 degrees (87-95), with +/- 3 degrees for 98.7%. T was 89.3 +/- 1.5 degrees
      (85-94) with +/- 3 degrees for 95.6%. PF was 88.6 +/- 1.6 degrees (84-93) for
      87%, PT was 87 +/- 2 degrees (81-93) with +/- 3 degrees for 94%. The four cuts
      were within +/- 3 degrees for 227 prostheses (77%), within +/- 2 degrees for 156
      (52%) and within +/- 1 degrees for 56 (18%). Measurements made again one year
      after implantation for 203 knees gave the same results. Operative time for
      implantation was 68 +/- 23 minutes for implantation and 85 +/- 23 minutes
      including complete closure (less than 60 minutes for 68 knees). DISCUSSION: The
      accuracy of each cut was satisfactory on average with a small standard deviation.
      Recent data in the literature show that the accuracy in our series is comparable
      with that obtained currently with navigation systems. In light of this
      experience, it can be seen that better precision can be achieved for each of the
      cuts. CONCLUSION: The accuracy of conventional instrumentation systems is still
      comparable with that obtained with computer-assisted surgery. The purpose of this
      study was not to question the benefit of navigation, but to establish a basis
      upon which progress can be measured. The results enabled a more realistic
      comparison of the precision of navigation systems and also can be comforting for
      operators still using conventional ancillaries.

PMID- 16910608
TI  - [Pedicle closing-wedge osteotomy for the treatment of fixed sagittal imbalance].
AB  - PURPOSE OF THE STUDY: The aim of this study was to analyze x-ray results in
      patients who underwent pedicle subtraction osteotomy for complex deformations
      (flat back, kyphosis) leading to fixed sagittal imbalance. MATERIAL AND METHODS:
      Thirty-four patients underwent surgery between 1996 and March 2003 in two
      centers, the orthopedic surgery unit devoted to spinal surgery and sports
      traumatology at the Strasbourg University Hospitals and the spinal surgery unit
      at the Chenove Clinic (Dijon). The series included 20 women and 14 men, mean age
      46.5 years (range 14-74 years) treated for: postoperative flat back (n = 19),
      kyphoscoliosis (n = 6), ankylosing spondylarthritis (n = 5), and malunion (n =
      4). After careful planning to achieve the necessary degree of correction, the
      patient was installed on a Cotrel table with a stable support enabling limited
      blood loss and facilitated reduction maneuvers via elevation of the lower limbs.
      The technique started by resection of the posterior arch, the transverse
      processes, and the pedicles, followed by partial resection of the body with a
      chisel under fluoroscopic control. The closure was achieved by in situ reduction
      with compressive rotation. Adjacent discs were then evaluated to search for any
      opening which could be filled by an anterior graft to complete the stabilization.
      The osteosynthesis used 2-, 4-, and 6-rod assemblies. The 6-rod assemblies
      enabled anchoring the fixation above and below before the osteotomy. Two prebent
      rods completed the assembly at reduction after osteotomy. Weight-bearing started
      on day 4. A protective corset was worn for three months by 19 patients. The
      patients resumed their occupational activities on average 6.73 months
      postoperatively without change in activity for 63%. Overall satisfaction was
      close to 90% excellent outcome. RESULTS: All clinical results were analyzed with
      the Profil software of Surgiview. X-ray data were analyzed with Spineview. A self
      administered clinical questionnaire was used to evaluate pain, result of the
      operation, and the impact on the patient's body image. On average, the wedge
      osteotomy measured 28.9 degrees for correction of lumbar lordosis by 31.5 degrees
      with a maximum of 65 degrees. The misalignment at C7 was reduced from 51 mm to 2
      mm. At the pelvic level, version improved 16 degrees, sacral slope 8 degrees.
      There were four dura mater breaches which had to be sutured, but with no clinical
      consequence (one progression to meningocele). Mean intraoperative blood loss was
      1400 cc (300-4500cc) for a mean operative time of 260 minutes (165-450 min).
      There were two early infections at day 15 postop which resolved with antibiotics.
      Four patients developed resolutive sciatica (n = 2) or cruralgia (n = 2) during
      the following months. The short-term follow-up revealed eight non-unions (25%)
      with rupture of osteosynthesis material and loss of correction. The opening in
      the adjacent discs and the insufficient posterior closure explained this
      mechanical complication. CONCLUSION: Pedicle subtraction osteotomy is an original
      operative technique reserved for specialized centers. A well-experienced team is
      needed to control the risks involved. Sagittal balance should be one of the
      important goals for modern spinal surgery.

PMID- 16910609
TI  - [Radiographic diagnosis of dislocated inverted shoulder prosthesis: two cases of
      unrecognized dislocation].
AB  - Dislocation of inverted shoulder prostheses are rarely described in the
      literature. Diagnosis is relatively difficult as illustrated by two cases
      reported here which went unrecognized. The problem is the absence of any clear
      clinical sign of dislocation and the rather difficult interpretation of the
      radiographic images. We propose a method for analyzing the radiographic images
      which can be used to confirm the absence of dislocation on the AP view.

PMID- 16910610
TI  - [Allograft-prosthesis composite arthroplasty for posttraumatic floating elbow].
AB  - Loss of bone stock in the elbow joint raises serious problems for reconstruction
      surgery. Total allograft-prosthesis composite arthroplasty is an attractive
      alternative to revision prosthesis and isolated osteoarticular allografts known
      to have many drawbacks. Use of this method is rather recent for revision
      procedures and tumor surgery and posttraumatic cases are rare (five reported
      cases). We report a case of posttraumatic floating elbow treated with this
      technique. At 75 months follow-up, the clinical result was excellent with the
      Mayo Clinic performance score at 100/100. Allograft-native bone fusion was
      complete and there were no complications, particularly no loosening. This
      composite technique is particularly well adapted for patients with major bone and
      joint loss. It can avoid the specific problems associated with each of the
      techniques used alone. The allograft reconstructs bone stock while the prosthetic
      component avoids the clinical expression of graft epiphyseal lysis.

PMID- 16910611
TI  - [Osteoid osteoma of the coccyx: a case report].
AB  - The spine is a rare localization of osteoid osteoma and the coccyx even more
      exceptional. We report a case of osteoid osteoma of the coccyx in a young man who
      consulted for sacrococcygeal pain partially relieved with salicylates. Computed
      tomography of the region demonstrated a typical osteoid osteoma lesion. CT-guided
      localization enabled complete resection of the nidus as demonstrated by the CT of
      the operative specimen Pathology confirmed the diagnosis of osteoid osteoma.
      Outcome has been quite favorable at two years.

PMID- 16910612
TI  - [Irreducible traumatic dislocation of the hip caused by labral and capsular
      entrapment with a buttonhole effect].
AB  - Irreducible hip dislocation following capsular and labral entrapment is a rare
      condition. We report a case of irreducible posterior traumatic pure hip
      dislocation where reduction was successfully achieved only with open surgery. An
      analysis of this case in the light of the published literature recalls the
      different etiologies of irreducible traumatic dislocation of the hip and the
      requirement for open surgery.

PMID- 16910613
TI  - [Traumatic rupture of the tibialis posterior tendon after ankle fracture: three
      cases and a review of the literature].
AB  - We report three cases of complete traumatic tibialis posterior tendon rupture
      which occurred after ankle fracture. Diagnosis was established at surgery. Repair
      of the non-degenerative tendon was achieved during the procedure for
      osteosynthesis of the malleolar fracture. Fractures healed a few months after
      surgery. The posterior tibialis muscle tendon functioned plantar arch was normal,
      except in one patient with multiple injuries who died in intensive care thirteen
      days after the accident. Although exceptional, injury of the tibialis posterior
      tendon should not be overlooked after ankle fracture. These injuries become
      apparent only at surgery for the malleolar fracture since pain hinders clinical
      examination. Primary suture best guarantees a good functional outcome. Residual
      pain, deficit in active inversion of the foot, modified medial longitudinal arch,
      or progression to planovalgus are retrospective diagnostic signs.

PMID- 16910614
TI  - [Every two year follow-up of arthroplasties: myth or reality?].
AB  - In this article, we propose a simple calculation to project quantitatively the
      number of consultations implied by a systematic follow-up protocol for
      arthroplasty surgery. In France, this surveillance schedule has become mandatory
      and will have a pertinent impact on health care expenditures. The longevity of
      implanted prostheses as well as patient life expectancies can be used to estimate
      the number of consultations necessary for a regular follow-up. For example, a
      surgeon who performs 200 arthroplasty procedures per year will have to see 17
      patients per week 20 years later.

PMID- 16910615
TI  - [The presence of emotionality].

PMID- 16910616
TI  - [Cortical-subcortical dysregulation: "hypo-limbic" syndromes].

PMID- 16910617
TI  - [Subcortical neural plasticity: potential therapeutic impact in depression].

PMID- 16910618
TI  - [Profound cerebral stimulation: its usefulness for the therapeutic modulation of
      behavior and emotions].

PMID- 16910619
TI  - [Impact of a new cognitive remediation strategy on interpersonal problem solving
      skills and social autonomy in schizophrenia].
AB  - INTRODUCTION: Despite recent developments, the impact of pharmacotherapy on
      social autonomy and interpersonal problem solving skills in patients with
      schizophrenia remains limited, with consequences in terms of socio-professional
      functioning. Indeed, independently of the positive, negative and/or
      disorganization symptoms, functional deficits in patients with schizophrenia rely
      mainly on various cognitive impairments. OBJECTIVES: To determine the impact of a
      new Cognitive Remediation Strategy on interpersonal problem solving skills,
      social autonomy and symptoms in patients with schizophrenia. METHODS: Thirty
      patients with schizophrenia were enrolled in a program consisting of 14 training
      sessions of 4 cognitive functions (attention/concentration, topological memory,
      logical reasoning, executive functions) using the REHACOM software. Measurements
      of attention (Continuous Performance Test, CPT), memory (Rivermead Behavioural
      Memory Test, RBMT) and executive functions (Wisconsin Card Sorting Test, WCST) as
      well as interpersonal problem solving skills (Assessment of Interpersonal Problem
      Solving Skills, AIPSS) and social autonomy (Social Autonomy Scale, EAS) and
      finally schizophrenia symptoms (Positive And Negative Syndrom Scale, PANSS) were
      undertaken at the beginning and the end of the 14 remediation meetings. RESULTS:
      Cognitive functions, interpersonal problems solving skills, social autonomy and
      symptoms were significantly improved by the Cognitive Remediation Strategy.
      CONCLUSION: Our results confirm the therapeutic impact of a Cognitive Remediation
      Strategy among 30 schizophrenic patients stabilised on clinical, therapeutic and
      functional levels. The question of the long-term maintenance of such improvements
      still requires further investigation.

PMID- 16910620
TI  - [Management of psychological disorders in patients with chronic hepatitis C].
AB  - BACKGROUND: Chronic hepatitis C remains a public heath problem. In France,
      400,000 to 500,000 subjects are chronically infected with HCV. LITERATURE
      FINDINGS: The purpose of this review was first to summarize the clinical aspects
      of the disease and the guidelines and results of antiviral treatment. The authors
      focus on the psychiatric side effects of antiviral treatment, and discuss the
      importance of good patient-provider interaction in patient's satisfaction,
      highlighting the mandatory role of the dynamic management of patients by
      hepatologists and psychiastrists. CONCLUSION: Multidisciplinary approaches have
      to be set up to better treat these patients.

PMID- 16910621
TI  - [Ethical foundations of institutional psychotherapy].
AB  - HISTORICAL ASPECTS: The idea behind this work is to have an ethical examination
      of the institutional psychotherapy movement which has long influenced French
      public psychiatry and which has progressively, since the 80s, been subject to
      growing doubts. In the first part, institutional psychotherapy is presented. It
      is a model for theoretical development and practice in psychiatric care. It came
      into being just following the end of the Second World War at the same time as
      modern medical ethics. Its principles come on the one hand, from recognition of
      asylums' pathogenic effects--which led to the crushing of the patient's being-
      and on the other, through recognition of the uniqueness of each person and the
      subjectivity of mental suffering. These elements gave rise to creativity within
      the world of medicine and, in the sector, generated the science of psychiatry
      which advocated for continuity in care (both inpatient and outpatient) and
      preventive work directed at the population. This movement called for the use of
      the institution in its dynamic aspect which promotes exchanges and allows
      patients to situate or resituate themselves in historic and symbolic dimensions.
      It privileges a high level of transversality, maximum communication, favouring
      speaking out loud and responsibility. It requires a permanent analysis of the
      institutional counter transference (emotional reactions of the caregivers
      involved, their interrelations and the social and material organization of the
      institution) which determines the therapeutic action itself. THEORICAL BASIS: In
      a second part, its theoretical foundations and its practice shall be investigated
      in light of the guiding concepts of medical ethics (justice, autonomy,
      beneficence, non-malfeasance). Institutional psychotherapy responds to the need
      for justice by considering the patient as a whole and by conceiving each patient
      as being like oneself despite the differences (associated with the mode of
      hospitalization, the social or diagnostic category). The principle of autonomy
      lies always at care's horizon, made concrete in practice by notions of
      habitability, orientation to place and time, references, by activities and by
      meetings. The principle of beneficence was the basis for round-the-clock intakes,
      the use of an established theoretical model and clinical practice centred on the
      patient's words. Institutional analysis attempts not to repeat the alienation
      felt by the patient, alienation being associated with the treatment environment,
      and draws from the principle of non-malfeasance. It therefore appears that the
      approach of institutional psychotherapy conforms with ethical requirements, given
      its major interest in the subject who aspires to find meaning in life. CURRENT
      SITUATION: The third part discusses current orientations in care related to the
      explosion in neuroscience and technology, the promotion of the citizen as an
      individual, and legal doctrine, budgetary constraints, and new demands made on
      psychiatry from the social and political domains. The widespread trend towards
      simplification, swollen with hypotheses from neuroscientific research, is
      progressively reducing mental illness to target symptoms. The recovery of the
      notion of citizenship through technological capture and ideological strains in
      contemporary culture have also affected a suspension of the subject as a thinking
      and desiring being, and exempted caregivers from considering transferral
      phenomena, indicated with the appearance of new signifiers: user, stress, plague,
      network. The new medical-technical jargon of scales, tables, and management
      participates in the same process of patient objectification and care
      compartmentalization. In this context, under the cover of science and generally
      good actions, psychiatry has become biologisized, whilst being diluted from its
      social aspect, even as it becomes more repressive for patients. CONCLUSION: This
      observation leads to the conclusion, in the fourth part, that there is a need for
      psychiatry, which within its own discipline has a hard time finding sufficient
      resources, to refocus itself ethically. This enlightenment could come within a
      multi-disciplinary ethical space, uniting practitioners and psychiatric
      caregivers, psychoanalysts, philosophers, sociologists, neurobiologists etc. The
      research should concern the legitimacy of the principles that underlie
      psychiatric action in its care and preventive aspects.

PMID- 16910622
TI  - [Post-traumatic stress disorder in survivors of the Agadir earthquake (Morocco)
      in 1960].
AB  - INTRODUCTION: Agadir City is geologically located on a seismic line. This city
      witnessed an earthquake in February 1960 with a magnitude of 6 degrees in Richter
      scale. During this disaster more than 17,000 people died and 60% of the town was
      destroyed. OBJECTIVES: Forty years later, the objective of this study was to
      assess post-traumatic stress disorders at the time of the disaster and currently
      among this population. METHODS: Two groups, matched by gender and age were
      included: 1) a group (G 1) of 80 earthquake survivors with an age varying from 45
      to 70 years ; 2) a control group (G2) with 80 people who experienced accidental
      events other than the earthquake. The instruments used were: a questionnaire
      concerning socio-demographic data, and the Post-traumatic Stress Diagnosis Scale
      Edna Foa-1995 for the diagnosis of PTSD which was translated in Moroccan Arabic
      language. The epidemiological survey was conducted in two steps during 13 months.
      The first step consisted in the inclusion of the first group: victims of the
      disaster. One hundred and two survivors were contacted and 80 accepted to
      participate in the study. The second step, concentrated on the inclusion of the
      other group, according to gender and age of the survivors group. All interviews
      were conducted in the homes of the participants. Data analysis was performed on a
      PC microcomputer using Epi info 6.04 French version (Center for disease control
      and prevention CDC, Atlanta, USA). The statistical analysis was based on the
      descriptive techniques of statistics. RESULTS: The main results were: 1) after
      the traumatic events and retrospectively, survivors from the earthquake had
      statistically more PTSD than G2: 38.8% vs 20%; 2) at the time of the study, the
      prevalence of PTSD between the two groups was not significantly different: 10%
      for the survivors of the earthquake vs 7.5% for G2 (victims of accidents) while
      the dates of trauma differed; 3) forty years later, the socio-professional life
      of the survivors was still perturbed. DISCUSSION: These results are in accordance
      with the literature, even if the methodological differences constitute a limiting
      factor for the comparison. Nevertheless, the persistence of symptoms of PTSD many
      years later might be explained by the severity of the trauma, the existence of
      external stimuli, such as the frequent tremors felt in Agadir, the noise, the
      storms, the earthquake happening in other cities...create a persistent state of
      hyper-vigilance which maintains and/or worsens the symptoms of PTSD. CONCLUSION:
      In conclusion, 40 years later, survivors are in need of care to overcome symptoms
      of PTSD. Preventive measures for victims of disasters should perhaps be
      developed.

PMID- 16910623
TI  - [Pregnancy, breast feeding and mood stabilisers: review and recommendations for
      practice].
AB  - INTRODUCTION: The high prevalence of bipolar affective disorder, the early age of
      onset and the even sex ratio imply that numerous women of childbearing age raise
      the question of mood stabilisers during pregnancy and breast feeding. LITERATURE
      FINDINGS: Some data suggest that giving appropriate answers to bipolar women who
      want to have children is an unmet need. We reviewed the risks and therapeutic
      options of this period of life in women with bipolar disorder. The generally
      accepted idea that pregnancy protects from relapses in bipolar disorders may be
      untrue and even deceitful. Lithium is the only mood stabiliser that can be
      prescribed in some cases during the first three months of pregnancy. DISCUSSION
      AND GUIDE LINES: We give explicit criteria that allow to consider this option: a
      severe illness prior to lithium prescription, a highly favourable outcome since
      initiation of lithium, no relapse during the last 18 months. When such conditions
      are satisfied, a reflection of the patient and at best of the couple must be
      proposed and associated with very complete information, both oral and written
      when possible, on the risks and benefits of the interruption and/or continuation
      of lithium. The teratogenic risks with anticonvulsants have been demonstrated and
      their prescription during the first three months of pregnancy should be avoided.
      Besides, there is some concern about the psycho-motor development of children
      born from women who were under anticonvulsants during pregnancy. The more recent
      mood stabilisers are not recommended either due to insufficient data. Breast
      feeding is not recommended under lithium, but seems safe under carbamazepine or
      valproate and its derivatives.

PMID- 16910624
TI  - [Headache and transformed migraine with medication overuse: what differences
      between disability, emotional distress and coping?].
AB  - LITERATURE FINDINGS: Twelve percent of general population is estimated to suffer
      from migraine (Henryet al., 2002), which represent in France 6 to 7 millions of
      individuals. Transformed migraine (TM) with medication overuse is a complication
      of migraine characterized by an increase of crisis frequency and by a parallel
      increase of medication intake. French prevalence of TM with analgesic overuse
      seems to reach up to 3% of general population (Lanteri-Minet, 2003). TM is
      associated with an increased disability (concerning housework, leisure, job and
      social activities). Moreover TM is associated with a bad emotional adjustment,
      which can lead to anxiety and depressive disorders. Those disorders have been
      founded to be more frequent in TM than in simple migraine (Radatet al., 1999). As
      a consequence, TM patients's quality of life is severely impaired. The use of
      dysfunctional coping strategies against pain should explain bad emotional
      adjustment in those patients. One study have found a statistical relationship
      between dysfunctional coping strategies such as nd depressive disorders in
      migraineurs (Materazzo et al., 2000). METHOD: The aim of this study was to
      compare 30 simple migraineurs (SM) to 32 transformed migraineurs with medication
      overuse (TM) for impairment, emotional adjustment and coping strategies. Patients
      have been assessed with Pain Disability Inventory (PDI) (Pollard et al., 1984),
      Hospital Anxiety Depression scale (HAD) (Zigmond and Snaith, 1983) and Coping
      Strategies Questionnaire (CSQ) (Rosentiel and Keefe, 1983). RESULTS: Principal
      Component Analysis (SPSS Software) confirms the good psychometric properties of
      PDI and HAD in headache patients. Statistical analysis shows higher emotional
      distress scores (HAD mean score = 32,2 +/- 10,9) in TM than in SM (24, 1 +/- 7,3)
      (p < 0,001). Both groups didn't use the same coping strategies against pain. TM
      were characterized by the use of "dramatisation", "distraction" and "pray", which
      are considered as dysfunctional coping strategies, although SM used
      "reinterpretation" which is associated with a better adjustment in term of
      disability and emotional distress (Riley et al., 1999). CONCLUSION: These results
      suggest that dysfunctional coping strategies in TM should explained the increased
      prevalence of emotional distress in this population. It should be of an utmost
      interest to assess temporal evolution of coping strategies after medication
      withdrawal. Withdrawal is the main therapeutical measure proposed to TM patients.
      It should also be supposed that behavioural changes related to medication with
      drawal evolve in parallel with changes in the use of coping strategies against
      pain.

PMID- 16910625
TI  - [Preliminary reports from a psychometric fixation-regression study using the
      McGill Object Relations Scale].
AB  - INTRODUCTION: Psychosexual development is generally assessed clinically, that is
      to say, in a qualitative manner (Piper and Duncan, 1999). Dymetryszyn, Bouchard,
      Bienvenu, De Carufel, and Gaston (1997) recently proposed a more quantitative
      approach based on the overall maturity of the subject's object relations.
      BACKGROUND: Object-relation maturity is quantified using a profile that defines a
      score for each stage of an individual's psychosexual development: oral
      narcissistic, oral-objectal, anal, phallic pre-oedipal, oedipal, and genital. The
      McGill Object Relations Scale (MORS) (Dymetryszyn et al., 1997) was adapted
      (Combalbert, Vautier, Bourdet-Loubere, Favard, & Bouchard, 2002) and then used to
      obtain the quantitative scores. The relationship between overall object-relation
      maturity and psychosexual development is complex. Psychosexual development is
      considered here to be a constant latent dimension. Accordingly, the higher the
      level of development, the greater the individual's possibility of establishing
      the object relations that correspond to more evolved stages. Inversely, the lower
      the level of development, the more the individual is forced to rely on object
      relations corresponding to earlier stages of development. However, the connection
      between the object-relation maturity profile and psychosexual development is made
      even more complex by the existence of the well-known phenomenon of fixation
      regression. OBJECTIVES: This article attempts to determine how fixation
      regression is reflected in the structure of the profiles of a sample of
      individuals whose clinical diagnosis suggests probable regression to the anal
      stage. METHODS: The subjects chosen had borderline personality disorder coupled
      with either perversion or psychopathy. The data were modelled using an unfolding
      model. MORS was used on 60 criminal subjects who had been charged with, or
      convicted of, crimes against persons. The nosographic diagnosis was based on the
      psychiatric assessment of the prisoners. DSM IV diagnostic criteria were used as
      a reference to confirm or refute the pronounced diagnosis. Only subjects who met
      at least five criteria for borderline personality disorder were included in the
      sample. To assess the reliability of the individual scores, two expert judges
      blindly scored the 60 protocols. RESULTS: The results obtained with an unfolding
      model support the hypothesis that the observed ordinates for the oral
      narcissistic, oral-objectal, phallic pre-oedipal, oedipal, and genital stages
      obey a law of synchrony that complies with the postulate of a continuum in
      psychosexual development. The second main result was the fact that the observed
      ordinates for the level corresponding to the anal stage could not be described by
      the model. Furthermore, this finding did not come from a possible scoring error,
      since inter-judge reliability was 0.93 for that level. DISCUSSION: These results
      are encouraging for the utilization of MORS as a technique for quantifying object
      relations. This study on a sample of individuals with a high probability of anal
      stage fixation-regression suggests that this type of phenomenon can be
      objectified by means of MORS profiles. However, the present study has some
      limitations of its own. The main methodological drawback pertains to the
      subjective aspect of the protocol scoring. The two judges had a great deal of
      joint experience in scoring other protocols on the MORS grid. This could explain
      the particularly high inter-judge correlations, compared to the within-class
      correlations published by Dymetryszyn et al. (1997). CONCLUSION: One cannot rule
      out the possibility that our analyses would have had different outcomes had other
      independent judges scored the 60 protocols. Moreover, our results cannot be
      generalized without replication. A critical test would be to replicate our
      analyses on similar data, and to examine the unfolding model's behavior on data
      from a sample of ordinary adults diagnosed as not having strong fixation
      regression tendencies. If the synchrony laws defined by the unfolding model are
      correct, the anal stage should be included in the arc formed by projecting the
      six stages on the factorial plane of the principal component analysis.
      Fundamental research based on the psychosexual theory of the libido and supported
      by statistical data can objectify the vicissitudes of psychosexual development
      (such as fixation-regression) or developmental differences across groups of
      individuals. This makes a strong case for pursuing MORS-based investigations.

PMID- 16910626
TI  - [Oxidative stress involvement in schizophrenia pathophysiology: a review].
AB  - BACKGROUND: Schizophrenia is a devastating psychiatric disorder with a broad
      range of behavioural and biologic manifestations. There are several clinical
      characteristics of the illness that have been consistently associated with poor
      premorbid adjustment, long duration of psychosis prior to treatment and prominent
      negative symptoms. The etiopathogenic mechanisms of lack of insight in patients
      with schizophrenia are to date unknown, although several hypotheses have been
      suggested. A point of convergence for the theoretical models occurs with regard
      to the neuronal membrane. Neuronal membrane contains a high proportion of
      polyunsaturated fatty acid and is the site for oxidative stress. Oxidative stress
      is a state when there is unbalance between the generation of reactive oxygen
      species and antioxidant defence capacity of the body. It is closely associated
      with a number of diseases including Parkinson's disease, Alzheimer-type dementia
      and Huntington's chorea. Accumulating evidence points to many interrelated
      mechanisms that increase production of reactive oxygen or decrease antioxidant
      protection in schizophrenic patients. OBJECTIVES: This review aims to summarize
      the perturbations in antioxidant protection systems during schizophrenia, their
      interrelationships with the characteristic clinics and therapeutics and the
      implications of these observations in the pathophysiology of schizophrenia are
      discussed. LITERATURE FINDINGS: In schizophrenia there is evidence for
      deregulation of free radical metabolism, as detected by abnormal activity of
      critical antioxidant enzymes (superoxide dismutase, glutathione peroxidase and
      catalase). Many studies conclude in the decrease in the activity of key
      antioxidant enzymes in schizophrenia. A few studies have examined levels of non
      enzymatic antioxidants such as plasma antioxidant proteins (albumin, bilirubine,
      uric acid) and trace elements. How showed decreased levels in schizophrenic
      patients. Others studies have provided evidence of oxidative membrane damage by
      examining levels of lipid peroxidation products. Such abnormalities have been
      associated with certain clinical symptoms and therapeutic features. Negative
      symptoms have been associated with low levels of GSH-Px. Positive symptoms have
      been positively correlated with SOD activity. Plasma TAS was significantly lower
      in drug-free and haloperidol treated patients with schizophrenia. A low
      erythrocyte SOD activity has been found in never-treated patients, but with
      haloperidol treatment, SOD activity increased. DISCUSSION: These results
      demonstrate altered membrane dynamics and antioxidant enzyme activity in
      schizophrenia. Membrane dysfunction can be secondary to free a radical-mediated
      pathology, and may contribute to specific aspects of the schizophrenia
      symptomatology. Membrane defects can significantly alter a broad range of
      membrane functions and presumably modify behavior through multiple downstream
      biological effects. Phospholipid metabolism in the brain may be perturbed in
      schizophrenia, with reduced amounts of phosphatidylcholins and
      phosphatidylethanolamine in post-mortem brain tissue from schizophrenic patients,
      and large amounts of lipofuscin-like materiel in the oligodendrocytes. The
      existence of these products within cell membranes results in an unstable membrane
      structure, altered membrane fluidity and permeability and impaired signal
      transduction. Recent findings suggest that multiple neurotransmitter systems may
      be faulty. CNS cells are more vulnerable to the toxic effects of free radicals
      because they have a high rate of catecholamine oxidative metabolic activity.
      Neurotransmitters, like glutamate, can induce the same metabolic processes that
      increase free radical production and can lead to impaired dopamine-glutamate
      balance. These results question the role of this imbalance in the biochemical
      basis evoked in the etipathogenic mechanisms of schizophrenia, as well as the
      role of antioxidants in the therapeutic strategy and their implication in
      preventive and early intervention approaches in populations at risk for
      schizophrenia.

PMID- 16910627
TI  - [Inhibition and resource capacity during normal aging: a confrontation of the
      dorsal-ventral and frontal models in a modified version of negative priming].
AB  - BACKGROUND: Over the past decades, cognitive psychology contribution to our
      understanding of aging relies on two major perspectives, focusing on the
      selective impact of age on either cognitive multiple-systems or global factors of
      cognition: slowing, working memory and inhibition. In the latter, reduction in
      inhibitory control during aging (in its access, deletion or restraint functions)
      is associated with poorer performance on a variety of tasks referring to memory,
      comprehension or language [Hasher, Zacks and May (16)]. The attractiveness of
      inhibition as an explanatory factor results in part in the absence of negative
      priming during aging. Negative priming refers to the slow down of latencies when
      individuals have to respond to recently ignored informations, compared to
      unrelated informations. The dissociation, between a preserved location negative
      priming and an absence of identity negative priming during aging, supports the
      dorsal-ventral model of inhibition which suggests that spatial and identity
      inhibition are supported by different and independent visual pathways. An
      alternative model, directly at odds, is that inhibitory mechanisms are supported
      by the frontal lobe. In this perspective, inhibition is not a central process
      responsible for the control of working memory contents, but an automatic and
      local mechanism whose triggering depends on controlled attention. Therefore,
      working memory drives efficient inhibition by sustaining task instructions and
      appropriate responses throughout task execution. This hypothesis is consistent
      with Houghton and Tipper's (17) architecture of selective attention. According to
      the authors, the presence or absence of automatic inhibition is very closely
      linked to a Match/Mismatch field whose function is to compare the present
      stimulus to an internal self-generated internal template. When an information
      fails to match the subject's current goals, the match/mismatch field causes an
      automatic inhibitory imbalance which reduces the to-be-ignored properties'
      responsiveness. In contrast, information matching subjects' goal is enhanced
      through an automatic excitatory imbalance. The accurate functioning of the
      Match/Mismatch field requires efficient executive functioning responsible for the
      uphold of goals and correct responses. In the case of negative priming,
      manipulating the efficiency of working memory is of interest as it should affect
      the triggering of slowing, ie, an indirect inhibitory deficit, when the task is
      resource demanding [Conwayet al. (6)]. Moreover, if inhibition, as reflected by
      negative priming, is mediated by individual resource capacity, then NP should
      disappear during aging only when individuals are engaged in a resource-demanding
      task. OBJECTIVES: To address this issue, we examine whether cognitive control
      load in a gender decision task contributed to the presence or absence of NP
      during aging. According to the dorsal-ventral model, task complexity should not
      have any impact on performance, since gender decision task relies on a conceptual
      analysis of information. In turn, the frontal model predicts that age differences
      in performance profile will only differ when individual resource capacity is
      overloaded. DESIGN OF THE STUDY: Sixty-four participants (32 young and 32 older
      adults) performed a gender categorisation task through two experiments. Trials
      involved two stimuli presented successively at the same location. A word served
      as a prime and a word as a target. Both prime and target could be male or female.
      When prime and target matched on gender, we talked about VALID pairs (or
      compatible). When prime and target mismatched on the manipulated features, we
      talked about INVALID pairs (or incompatible). Participants' task was to identify
      the gender of the target. They were explicitly instructed not to respond to
      primes but to read them silently. Our interest was in response latencies for
      valid versus invalid pairs. We manipulated task complexity by the absence
      (experiment 1) or presence (experiment 2) of a distractor during probe trials.
      RESULTS: For younger adults, primes presented before targets gave rise to
      behavioural costs when pairs were mapped to the same response compared to pairs
      that were mapped to opposite ones. This slowing, called Negative Compatibility
      Effect (NCE), was independent of the presence or absence of a distractor. NCE was
      reliable for the elderly patients only under condition of no interfering
      information during the probe trial: pattern of performance of older participants
      was identical to that of young adults (experiment 1). This effect disappeared as
      task complexity increased (experiment 2). DISCUSSION: This result suggests that
      NCE triggering is dependant on the amount of cognitive control engaged by the
      task, and therefore that the ability to inhibit irrelevant information is
      secondary to a general capacity of the working memory. CONCLUSION: The
      implications of our data are consistent with the level of processing account, as
      well as the recent neuroimaging contributions which suggest, for example, the
      involvement of the dorso-lateral prefrontal cortex (sensitive to aging) when task
      demands are high, and a ventro-lateral prefrontal implication when demands are
      low [see Eenshuistra et al. for a review (10)].

PMID- 16910628
TI  - [Use of antidepressant drugs in schizophrenic patients with depression].
AB  - INTRODUCTION: Depression is common in people with schizophrenia and is associated
      with substantial morbidity explaining also the considerable attention and
      recognition of this entity as suggested by the inclusion of the post-psychotic
      depression in DSM IV and ICD 10. The prevalence of this disorder varies according
      to the type of approach used (range between 7% to 75%). Prescription of
      antidepressants plus antipsychotic treatment is frequent in clinical practice (11
      to 43%). BACKGROUND: Pharmacokinetic and metabolic interactions have been
      identified. The cytochrome P450 has been identified as being implicated in the
      metabolism of most psychotropics, mainly through the CYP1A2, CYP2C19, CYP2D6,
      CYP3A4 isoenzymes. Tricyclic antidepressants are likely to increase
      chlorpromazine plasma levels. Similarly, antipsychotics such as perphenazine,
      chlorpromazine or haloperidol can increase antidepressant plasma levels, through
      the inhibition of CYP 450 isoenzymes (CYP2D6). Most of the Specific Serotonin
      Recapture Inhibitors (SSRIs) are likely to inhibit one or several CYP450
      isoenzymes. The inhibition is moderate to marked for CYP1A2 (fluvoxamine and
      fluoxetine), CYP2C19 (fluoxetine, fluvoxamine and sertraline), CYP2D6
      (paroxetine, fluoxetine and sertraline), and CYP3A4 (fluvoxamine, fluoxetine and
      sertraline). In the US, one-fourth of psychiatrists report the use of depression
      rating scales in schizophrenic patients. Non specific scales (Hamilton Depression
      Rating Scale or Beck Depression Inventory) are the most commonly used in spite of
      the fact that these scales do not allow the distinction of depressive from
      negative symptoms in schizophrenic patients. LITERATURE FINDINGS: Due to these
      limitations, more specific assessment tools for depressive symptoms in
      schizophrenia are required. Two specific scales for assessing depressive symptoms
      in schizophrenic patients have been constructed and validated. The Calgary
      Depression Scale (CDS) is a nine item scale, each item scored from 0 to 3. This
      scale was derived from the HDRS and the Present State Examination. Factor
      analysis showed that the CDS is unidimensional, has high internal consistency,
      and significant strong correlation with scores on the HDRS, Beck and BPRS
      depression scales. The CDS has been validated in different languages (Brazilian,
      Danish, French...). It has been shown that there is no overlap between negative
      or extrapyramidal and depressive symptoms assessed by the PDS in schizophrenic
      patients. The Psychotic Depression Scale (PDS) is a 32 item scale derived from
      the HDRS, PANSS, CPRS and AMDP, each item being rated from 0 to 7. A principal
      component analysis of the PDS items using a Varimax rotation disclosed 8
      orthogonal components that account for 71% of the variance. These components
      involved the following dimensions : depressive mood, inhibition, vegetative
      signs, paranoid signs, strangeness of thought, inverse vegetative signs, guilt
      feelings and cognitive signs. The analysis revealed that the 'depressive mood'
      factor of the PDS was correlated with the 'depressive' factor and was slightly
      correlated with the cognitive factor of the PANSS. This first factor was not
      correlated with either the "negative" factor of the PANSS, or the Positive or
      Excitement factor of the PANSS. Hence, this PDS, factor distinguished depressive
      signs from negative symptoms. Due to their metrologic properties, specific scales
      should be preferred. However, only one open trial (of an antipsychotic) and two
      double blind controlled trials (one comparison of 2 antipsychotics and one
      comparison of an cholinesterase inhibitor versus placebo) have been published
      using the CDS. Likewise, only one double blind controlled trial using the PDS
      (comparison of 2 antipsychotics) has been published. No study of the effect of
      antidepressants in depressed schizophrenic patients has been published, using
      either the CDS or the PDS assessment criteria. DISCUSSION: These specific scales
      are rarely used in clinical practice. Only about 1% of the US psychiatrists
      reported the use of the Calgary Depression Scale. Several open clinical trials
      have assessed the efficacy of antidepressant agents added to antipsychotic in
      patients with schizophrenia. They have produced inconsistent results but have
      suffered from methodological limits (short duration of the studies, non
      homogeneous inclusion criteria, heterogeneous assessment methods...). Due to the
      lack of a reference drug, double blind placebo-controlled trial are necessary. A
      recent meta-analysis has been performed on results of trials that have
      investigated the clinical efficacy of antidepressant medication (either
      tricyclics, SSRIs or others) in the treatment of depression in schizophrenic
      patients. In a subset of 5 trials (209 patients), the proportion improved in the
      antidepressant group was 26% (95% CI 10 to 42) higher than in the placebo group.
      The estimated number needed to treat was 4. In a subgroup of 6 studies (267
      patients), the standardized mean difference on the HDRS score was -0.27 (95% CI -
      0.7 to -0.2). There was no evidence that antidepressant treatment induced a
      deterioration of psychotic symptoms in these trials. CONCLUSION: The results
      provide weak evidence for the efficacy of antidepressants in patients with
      schizophrenia and depression. Today, the only SSRI tested in the treatment of
      depression in schizophrenic patients is sertraline. One study led to positive
      results. Since the meta-analysis, one additional study has been performed
      comparing sertraline to placebo. No difference between the 2 treatment groups was
      demonstrated but the power of the trial was rather low. Further research is
      required to determine the best approach towards treating depression in patients
      with schizophrenia, with clinical trials performed for longer periods, using
      appropriate assessment criteria such as depressive symptoms and quality of life.

PMID- 16910631
TI  - An ordered mesoporous aluminosilicate with completely crystalline zeolite wall
      structure.
AB  - An ordered mesoporous aluminosilicate with completely crystalline zeolite pore
      wall structure, denoted as OMZ-1, was successfully synthesized by
      recrystallization of SBA-15 using in situ formed CMK-5 as the hard template. The
      role of carbon material not only serves as a hard template to preserve ordered
      mesoporous structure but also kinetically controls the crystallization process to
      form large crystals.

PMID- 16910629
TI  - [Safety and efficacy of oral escitalopram as continuation treatment of
      intravenous citalopram, in patients with major depressive disorder--the navigade
      switch study].
AB  - Intravenous (iv) administration of an antidepressant is a common practice in some
      European countries, particularly in France, Spain, and Italy in the initial
      treatment phase of hospitalised, severe depressed patients. After a beneficial
      response is observed, patients are switched to an oral formulation. The approved
      treatment period of the iv form of citalopram is limited to 8-10 days. The high
      bioavailability of citalopram permits the use of identical iv and oral doses.
      Citalopram is a racemate, consisting of a 1:1 mixture of the S- and R
      enantiomers. The therapeutically active component is the S-enantiomer
      (escitalopram). Pharmacokinetic single dose administration studies in healthy
      subjects have demonstrated that daily oral administration of 20 mg of
      escitalopram or 40 mg citalopram results in similar plasma concentrations of the
      S-enantiomer of citalopram. This open-label multicentre French prospective study
      investigated the tolerability and efficacy of oral escitalopram 10 and 20 mg/day,
      administered for a 6-week period as continuation treatment of citalopram (20 mg
      or 40 mg daily) intravenous (iv), in patients with Major Depressive Disorder. A
      total of 171 patients were enrolled, of whom 147 (85%) completed the study. The
      mean MADRS score at inclusion (last citalopram dose) was 31.6 +/- 9.9. The total
      MADRS score decreased after 3 days of oral treatment with escitalopram.
      Escitalopram demonstrated a continuous effect in treating depressive symptoms
      throughout the study. The decrease in MADRS mean total score from baseline was
      statistically significant to each visit (day 3, 15; p < 0.0001). At final visit
      (J42), the decrease was - 18.9 +/- 11.7 (p < 0.0001) and the MADRS mean total
      score was 12.7 +/- 9.3. There were no differences seen in the patient response
      comparing gender, age, and the single or recurrent episodes. The changes of
      Clinical Global Impression scores (CGI-S, CGI-I, PGE-Patient Global Evaluation)
      were also indicative of an improvement of the patients' depression. The CGI-I and
      PGE scores were significantly correlated indicating good agreement between
      investigator and patient in rating the degree of improvement. At the end of the
      study, 67% of patients were classified as responders (decrease of MADRS score
      from baseline > or = 50%), and the majority of them were considered remitters
      (final MADRS score < or = 12). Overall, the switch from intravenous citalopram to
      oral escitalopram was well tolerated in the study population. In all, 57 patients
      (33%) reported at least one adverse event (AE) during the study (21 patients in
      the 10 mg group and 36 patients in the 20 mg group); of these, 7 patients (4%)
      withdrew from the study. The most frequently reported AEs were suggestive of
      residual symptoms of depression (anxiety, 9%; insomnia, 5% of patients). In
      conclusion, in this study oral escitalopram (10 mg or 20 mg) was well tolerated
      as continuation treatment after switching from intravenous citalopram (20 mg or
      40 mg). From the efficacy and safety data of this study, it can be concluded that
      the switch from citalopram iv to oral escitalopram (10 and 20 mg/day) is
      effective in decreasing depressive symptoms, and could be safely proposed in
      patients with major depressive disorder.

PMID- 16910632
TI  - Glycosylated foldamers to probe the carbohydrate-carbohydrate interaction.
AB  - The synthesis of a triglycosylated helical foldamer based on a combination of
      cyclopentyl- and pyrrolidinyl-based amino acids is described. This structure is
      stable in water, maintaining as it does a series of carbohydrate units in
      proximity to one another, and represents the basis of a new approach to the study
      of carbohydrate-carbohydrate interactions.

PMID- 16910633
TI  - Mechanism-based molecular design of highly selective fluorescence probes for
      nitrative stress.
AB  - Nitrative stress is implicated in various pathogenic processes, including
      neurodegenerative disorders, but there is no practical fluorescence probe which
      can monitor the generation of nitrative stress with high selectivity. To design a
      suitable fluorescence probe, we have first focused on the fluorescence quenching
      mechanism of the nitro group, which has been believed to be a unique quencher of
      fluorescent dyes. We found that nitro group-based fluorescence quenching could be
      explained in terms of an electron transfer process, from the excited fluorophore
      to the electron-deficient aromatic nitro moiety. By utilizing this result, we
      succeeded in developing novel fluorogenic probes, NiSPYs, which can selectively
      monitor the generation of nitrative stress based on aromatic nitration. NiSPYs
      showed strong fluorescence enhancement upon the reaction with nitrating agents,
      including peroxynitrite, but showed little or no fluorescence augmentation in the
      presence of other reactive oxygen species. NiSPYs should be potentially useful as
      tools to study the role of nitrative stress in various biological applications.

PMID- 16910634
TI  - Propagation of conformation in the surface-aligned dissociation of single
      CH3SSCH3 molecules on Au(111).
AB  - Single CH3SSCH3 molecules adsorb on the Au(111) surface in a trans-conformation.
      Subsequent electron-induced dissociation of CH3SSCH3 cleaves the S-S bond and
      produces a pair of CH3S fragments. The dissociation process was found to preserve
      the conformation of the parent molecule with a high probability of 75% and
      imprint it in the relative position and orientation of the product CH3S species
      on the surface. The high probability of the conformation-retaining scenario is
      likely due to surface alignment of the S-S bond-breaking reaction coordinate.

PMID- 16910635
TI  - d8 rhodium and iridium complexes of corannulene.
AB  - [(COE)2M]+ fragments (M = Rh, Ir; COE = cyclooctene) react with corannulene to
      give eta6-bound complexes [(COE)2Rh(eta6-C20H10)]PF6 and [(COE)2Ir(eta6
      C20H10)]PF6. Both compounds were characterized by X-ray diffraction studies, and
      binding in the solid state is compared with that of their aromatic analogues
      [(COE)2M(eta6-arene)]PF6 (aryl = benzene and phenanthrene). Solution NMR studies
      show that the [(COE)2Rh]+ fragment walks over the curved aromatic surface of
      corannulene, whereas the Ir analogue is not fluxional. Experimental as well as
      computational studies suggest that inter-ring movement of the Rh complex follows
      a hub migration mechanism. Initial reactivity studies indicate that the
      [(COE)2M]+ fragments can undergo chemical transformations, such as transfer
      dehydrogenation and substitution reactions, while still bound to corannulene.

PMID- 16910636
TI  - A single CH/pi weak hydrogen bond governs stability and the photocycle of the
      photoactive yellow protein.
AB  - Importance of the CH/pi interaction on the structure and function of the
      photoactive yellow protein (PYP) was substantiated. Focusing on the phenyl ring
      of Phe6 adjacent to the alkyl chain of Lys123, the mutants for these amino acid
      residues were characterized. The results demonstrated that the mutants lacking
      the pi-electron at position 6 or the alkyl chain at position 123 show substantial
      malfunction. This is a clear example that single CH/pi weak interaction plays a
      crucial role in the normal action of the protein.

PMID- 16910637
TI  - "Cymothoe sangaris": an extremely stable and highly luminescent 1,2
      hydroxypyridinonate chelate of Eu(III).
AB  - The synthesis, structure, and characterization of a new class of luminescent
      agents based on the 1,2-hydroxypyridinone chelator are reported. The prototype
      complex, [Eu(5LIO-1,2-HOPO)2]-, demonstrates superb aqueous stability [pEu =
      18.64(10)] and is highly emissive [Phit = 0.21(3)], emitting almost pure "red"
      light (lambdaem = 612 nm). The crystal structure reveals a coordination geometry
      reminiscent of a "butterfly", hence the soubriquet of "Cymothoe sangaris" to
      identify with the unique species of red butterfly found only in Central Africa.

PMID- 16910638
TI  - Cyclic peptide helices: a hybrid beta-hairpin/beta-helical supersecondary
      structure.
AB  - This communication describes the design and characterization of a new peptide
      motif that is a hybrid of beta-hairpin and beta-helical structures. This motif
      was supported by CD and IR spectrocopies in nonpolar organic solvents and was
      confirmed by NMR spectroscopy and structure calculations using NMR-derived
      restraints. The beta-hairpin/beta-helical motif represents a potentially
      attractive new structural template for a variety of possible applications in
      biomolecular design, such as ligands for macromolecular targets and building
      blocks for new protein architectures.

PMID- 16910639
TI  - Cold denaturation of encapsulated ubiquitin.
AB  - Theoretical considerations suggest that protein cold denaturation can potentially
      provide a means to explore the cooperative substructure of proteins. Protein cold
      denaturation is generally predicted to occur well below the freezing point of
      water. Here NMR spectroscopy of ubiquitin encapsulated in reverse micelles
      dissolved in low viscosity alkanes is used to follow cold-induced unfolding to
      temperatures below -25 degrees C. Comparison of cold-induced structural
      transitions in a variety of reverse micelle-buffer systems indicate that protein
      surfactant interactions are negligible and allow the direct observation of the
      multistate cold-induced unfolding of the protein.

PMID- 16910640
TI  - Detection of peptide-phospholipid interaction sites in bilayer membranes by 13C
      NMR spectroscopy: observation of 2H/31P-selective 1H-depolarization under magic
      angle spinning.
AB  - We have developed a solid-state NMR method for observing the signals due to 13C
      spins of a peptide in the close vicinity of 31P and 2H spins in deuterated
      phospholipid bilayers. The signal intensities in 13C high-resolution NMR spectra
      directly indicate the depolarization of 1H by 1H-31P and 1H-2H dipolar couplings
      under multiple-contact cross-polarization. This method was applied to a fully 13C
      , 15N-labeled 14-residue peptide, mastoparan-X (MP-X), bound to phospholipid
      bilayers whose fatty acyl chains are deuterated. The 13C NMR spectra for the
      depolarization were simulated from the chemical shifts and structure of membrane
      bound MP-X previously determined and the distribution of 2H and 31P spins in
      lipid bilayers. The minimization of RMSD between the simulated and the
      experimental spectra showed that the amphiphilic alpha-helix of MP-X was located
      in the interface between the water layer and the hydrophobic domain of the
      bilayer, with nonpolar residues facing the phosphorus atoms and alkyl chains of
      the lipids.

PMID- 16910641
TI  - Contrasting solvent and capping ligand effects directing the photochemistry of
      uranyl(VI) Schiff base complexes.
AB  - Photolysis of the uranyl(VI) Schiff base complex UO2(tBu4-salphen)(THF) (1a) with
      cobaltocene in THF affords [Cp2Co][UO2(tBu4-salphen)(OH)] (2) in high yield while
      irradiation in toluene yields no reaction. Electronic emission spectra of 1a
      reveal a large Stokes' shift in toluene similar to that observed in the free
      ligand, while in THF the structural rearrangement responsible for this shift is
      blocked. Instead, the ligand-centered excited state is redirected to the
      uranyl(VI) center by way of energy transfer, thus generating 2 from the
      intramolecular activation of a coordinated THF molecule.

PMID- 16910642
TI  - Ni/NiO core/shell nanoparticles for selective binding and magnetic separation of
      histidine-tagged proteins.
AB  - Ni/NiO core/shell nanoparticles having high affinity with polyhistidine were
      synthesized by decomposition of a Ni surfactant complex followed by air
      oxidation. Ni/NiO nanoparticles showed selective and efficient binding to
      histidine-tagged proteins and easy separation by using a magnet. These provided a
      more convenient way to efficient purification of histidine-tagged proteins
      compared with the conventional Ni-NTA complex-bound resins and microbeads.

PMID- 16910643
TI  - A biosynthetic gene cluster for the acetyl-CoA carboxylase inhibitor andrimid.
AB  - Increasing bacterial resistance to antibiotics with conventional targets has
      focused attention on antibiotics with unconventional targets. One promising
      candidate, the acetyl-CoA carboxylase (ACC) inhibitor andrimid, is a potent,
      broad-spectrum antibiotic with high selectivity for prokaryotic ACC. Here, we
      report the use of a DNA-based approach to clone the andrimid biosynthetic gene
      cluster from Pantoea agglomerans, yielding a cosmid that confers robust andrimid
      production on Escherichia coli. This gene cluster encodes a hybrid nonribosomal
      peptide/polyketide (NRP/PK) synthase with several unusual features, including
      three enzymes that form and insert beta-phenylalanine, two transglutaminase-like
      enzymes that likely serve as condensation catalysts, and four densely hybrid
      modules that form the succinimide precursor. Unlike most type I NRPSs and PKSs,
      the andrimid gene cluster is a dissociated system comprised of small proteins.
      Therefore, future efforts can exploit the genetic manipulability of E. coli to
      engineer the andrimid synthase with the goal of producing a diverse set of
      andrimid analogues for clinical evaluation.

PMID- 16910644
TI  - Synthesis of imidazoles through the copper-catalyzed cross-cycloaddition between
      two different isocyanides.
AB  - The copper-catalyzed reaction between two different isocyanides produces the
      corresponding heteroaromatization products, imidazoles, in good yields. The
      reaction proceeds most probably through the activation of the sp3 C-H bond in the
      isocyanides by a copper catalyst, followed by a [3 + 2] cycloaddition between the
      cuprioisocyanide intermediates and arylisocyanides.

PMID- 16910646
TI  - N-benzyl-2,3-oxazolidinone as a glycosyl donor for selective alpha-glycosylation
      and one-pot oligosaccharide synthesis involving 1,2-cis-glycosylation.
AB  - Glycosylation reactions using N-benzyl-2,3-trans-oxazolidinones as the glycosyl
      donors were shown to be highly alpha-selective. Advantages of the donor include
      facile preparation in gram-scale preparation and simple deprotection procedures.
      Subsequently, a one-pot oligosaccharide synthesis involving 1,2-cis glycosidic
      linkages was demonstrated using the novel glycosyl donors.

PMID- 16910647
TI  - Visible light-driven water oxidation by Ir oxide clusters coupled to single Cr
      centers in mesoporous silica.
AB  - Visible light-induced water oxidation has been demonstrated at an Ir oxide
      nanocluster coupled to a single CrVI site on the pore surface of MCM-41
      mesoporous silica. The photocatalytic unit was assembled by the reaction of
      surface Cr=O groups with Ir(acac)3 precursor followed by calcination at 300
      degrees C and bond formation monitored by FT-Raman and FT-IR spectroscopy. High
      resolution Z-contrast electron micrographs of the calcined material combined with
      energy-dispersive X-ray spot analysis confirmed the occlusion of Ir oxide
      nanoparticles inside the mesopores. Oxygen evolution of an aqueous suspension of
      the IrxOy-CrMCM-41 upon visible light irradiation of the CrVI-O ligand-to-metal
      charge-transfer absorption was monitored mass-spectrometrically. Comparison of
      the product yields for samples with low Cr content (Cr/Si </= 0.02) and high Cr
      content (Cr/Si = 0.05) indicates that only isolated Cr centers are capable of
      extracting electrons from Ir oxide clusters, while di- or polychromate species
      are not. Water oxidation at a multielectron-transfer catalyst coupled to a single
      metal center has not been demonstrated before. The ability to drive water
      oxidation with a single metal center as electron pump offers opportunities for
      coupling the oxygen-evolving photocatalytic unit to reducing sites in the
      nanoporous scaffold.

PMID- 16910645
TI  - Gold-catalyzed intramolecular allylation of silyl alkynes induced by silane
      alcoholysis.
AB  - The activation of alkynyl allyl silanes with a cationic gold catalyst in the
      presence of alcohols provides vinyl silanes that contain the allyl group at the
      beta-position and the alkoxysilyl group in cis-orientation. The bond
      reorganization process is most consistent with the involvement of a carbocationic
      intermediate, which undergoes a nucleophilic attack by an alcohol selectively at
      the silicon center. The cis-vinyl silyl ether products can be further elaborated
      by ring-closing and cross metathesis to form more substituted 1,4-dienyl silanes.

PMID- 16910648
TI  - Benzyl (phenyl) gamma- and delta-lactones via photoinduced tandem Ar-C, C-O bond
      formation.
AB  - A convenient metal-free procedure for the preparation of benzyl (phenyl) gamma-
      and delta-lactones is illustrated. This method is based on the photochemical
      generation of phenyl cations and their reaction with 3, 4, or 5-alkenoic acids.
      This leads to a phenyl- or benzyl-substituted lactone by tandem formation of an
      aryl-C and C-O bond. The intermediacy of a phenonium ion imparts a full regio-
      and stereoselectivity to the reaction.

PMID- 16910649
TI  - Rieske protein from Thermus thermophilus: 15N NMR titration study demonstrates
      the role of iron-ligated histidines in the pH dependence of the reduction
      potential.
AB  - A unique feature of Rieske proteins is the pH dependence of their reduction
      potentials. It has been proposed that protonation of the Nepsilon2 atoms of the
      two histidine rings ligated to the iron-sulfur cluster is coupled with cluster
      reduction (electron transfer). We have incorporated [15Ndelta1, 15Nepsilon2]
      histidine into the Rieske protein from Thermus thermophilis and have used 15N NMR
      spectroscopy to determine the pKa values of the histidine residues in the
      oxidized state of the protein. As expected from studies of a Rieske-type
      ferredoxin, the signals from the 15Ndelta1 atoms directly bound to iron were too
      broad to be detected, but broad signals could be detected from the 15Nepsilon2
      atom of each of the ligated histidine rings. We measured the chemical shifts of
      these signals as a function of pH between pH 6 and pH 12 and fitted them to
      theoretical titration curves. The results yielded well-separated pKa values for
      the two histidines (7.46 and 9.24), with Hill coefficients close to unity. The
      pKa values are in excellent agreement with values predicted from the pH
      dependence of the reduction potentials (7.85 and 9.65).

PMID- 16910650
TI  - Highly enantioselective reductive cyclization of acetylenic aldehydes via rhodium
      catalyzed asymmetric hydrogenation.
AB  - Catalytic hydrogenation of acetylenic aldehydes 1a-12a using chirally modified
      cationic rhodium catalysts enables highly enantioselective reductive cyclization
      to afford cyclic allylic alcohols 1b-12b. Using an achiral hydrogenation
      catalyst, the chiral racemic acetylenic aldehydes 13a-15a engage in highly syn
      diastereoselective reductive cyclizations to afford cyclic allylic alcohols 13b
      15b. Ozonolysis of cyclization products 7b and 9b allows access to optically
      enriched alpha-hydroxy ketones 7c and 9c. Reductive cyclization of enyne 7a under
      a deuterium atmosphere provides the monodeuterated product deuterio-7b,
      consistent with a catalytic mechanism involving alkyne-carbonyl oxidative
      coupling followed by hydrogenolytic cleavage of the resulting oxametallacycle.
      These hydrogen-mediated transformations represent the first examples of the
      enantioselective reductive cyclization of acetylenic aldehydes.

PMID- 16910651
TI  - Synthesis and stabilization of monodisperse Fe nanoparticles.
AB  - Monodisperse Fe nanoparticles are synthesized via a simple one-pot thermal
      decomposition of Fe(CO)5 in the presence of oleylamine. Controlled oxidation of
      the iron surface leads to crystalline Fe3O4 shell and results in dramatic
      increase of chemical and dispersion stability of the nanoparticles. Surface
      ligand exchange is readily applied to transfer the core/shell nanoparticles from
      hydrophobic to hydrophilic, and a stable aqueous nanoparticle dispersion in PBS
      is formed. The functionalized nanoparticles are suitable for biomolecule
      attachment and biomedical applications.

PMID- 16910652
TI  - The interaction of water with MOF-5 simulated by molecular dynamics.
AB  - Force field parameters for use with metal-organic framework-5 (MOF-5 or IRMOF-1)
      are presented. Flexibility within the framework is included in this model, so
      that structural changes upon interaction with adsorbate molecules can be observed
      and quantified. The model was validated by comparing simulated lattice parameters
      of pure MOF-5 with X-ray diffraction results. For the first time, molecular
      dynamics simulations have been performed that show how water interacts with MOF
      5. The framework is stable at water contents up to 2.3% by mass, but distortion
      in the lattice structure is already evident. At water contents of 3.9% and
      higher, the framework collapses because of the replacement of MOF O atoms by
      water O atoms in the Zn coordination shells. As a result, inorganic MOF O atoms
      are no longer coordinated by four Zn ions, and benzene dicarboxylate linkers are
      no longer tethered to Zn centers.

PMID- 16910653
TI  - Photoinduced charge-transfer states in subphthalocyanine-ferrocene dyads.
AB  - Very efficient stabilization of the photoinduced charge-transfer state was
      achieved in simple subphthalocyanine-ferrocene dyads, reaching radical pair
      lifetimes of about 0.2 ms.

PMID- 16910654
TI  - Observation of intramolecular paramagnetic T1 spin decoupling in the 13C NMR
      spectra of triazacyclohexane complexes of Ni(II).
AB  - N-Benzyl-substituted complexes [(triazacyclohexane)Ni(NCMe)3](BF4)2 and their
      diamagnetic zinc analogues have been prepared and characterized by X-ray
      crystallography. The T1 spin decoupling observed in their paramagnetic 13C NMR
      spectra can be quantitatively described by newly derived expressions that allow
      an independent determination of T2 of the 13C signal, T1 of the attached H or F,
      and the 1J coupling constant by line shape analysis.

PMID- 16910655
TI  - Stochastic detection of enantiomers.
AB  - The rapid quantification of the enantiomers of small chiral molecules is very
      important, notably in pharmacology. Here, we show that the enantiomers of drug
      molecules can be distinguished by stochastic sensing, a single-molecule detection
      technique. The sensing element is an engineered alpha-hemolysin protein pore,
      fitted with a beta-cyclodextrin adapter. By using the approach, the enantiomeric
      composition of samples of ibuprofen and thalidomide can be determined in less
      than 1 s.

PMID- 16910656
TI  - Selective sensing of metalloproteins from nonselective binding using a
      fluorogenic amphiphilic polymer.
AB  - Nonconjugated fluorogenic amphiphilic polymers containing an anthracene
      chromophore exhibit fluorescence quenching in the presence of metalloproteins,
      although the binding of the polymer to proteins is not selective. The reason for
      this difference is that the possible conformational changes that protein binding
      could bring about on a polymer do not affect the fluorescence properties of a
      pendent chromophore in nonconjugated polymers. This is in contrast to the
      nonspecific binding and response found with conjugated polymers to proteins.

PMID- 16910657
TI  - Water-soluble through-bond energy transfer cassettes for intracellular imaging.
AB  - A special, water-soluble, fluorescent probe 1 was designed. This consisted of a
      fluorescein-based component to harvest irradiation at 488 nm and a rhodamine
      based part designed to emit it at a significantly longer wavelength. This
      cassette was used to label an illustrative protein called ACBP. Evidence was
      accumulated to support the assertion that ACBP-1 bound its native ligand with a
      binding constant similar to that of the unlabeled protein, and retained its
      secondary structure (CD). ACBP-1 was imported into cells using the Chariot
      peptide. Confocal images proved that some ACBP-1 localized into the nucleus (as
      expected) and, most significantly, it could be visualized more effectively by
      irradiating at the donor (fluorescein-like) part of the cassette, than the
      acceptor (rhodamine-like) part. Overall, this study demonstrates that cassettes
      of this kind can label a protein without significantly perturbing its function or
      secondary structure and they can be visualized effectively via irradiation of the
      donor and observation of the acceptor fluorescence.

PMID- 16910658
TI  - Sensing of chiral fullerenes by a cyclic host with an asymmetrically distorted pi
      electronic component.
AB  - Upon inclusion complexation with a racemic mixture of chiral fullerene C76 ((+/-)
      C76), a novel cyclic host (1Rh) composed of a chiral N-methylporphyrin (PNMe) and
      a methylrhodium porphyrin (PRh) exhibited at 20 degrees C a 1H NMR spectral
      profile with diastereoisomerically split signals due to the NH group of PNMe. In
      contrast, because of a faster guest exchange dynamics, metal-free reference 12H,
      under identical conditions, did not show any signature of such diastereoisomeric
      splitting. Owing to the excellent resolution (15.6 Hz) of the split NH signals,
      the complexation with 1Rh allowed for the accurate determination of the optical
      purity of C76. On the basis of the 1H NMR spectral profiles of 1Rh in toluene-d8
      at 20 degrees C in the presence of enantiomer mixtures of C76 of different
      optical purities, an absolute Deltaepsilon value of 58.5 M-1 cm-1 at 330 nm was
      obtained for enantiomerically pure C76.

PMID- 16910659
TI  - Clamshell structure of Sc(biphenyl) from high resolution photoelectron
      spectroscopy.
AB  - Sc(biphenyl) is produced in a laser vaporization molecular beam source and
      characterized by pulsed field ionization-zero electron kinetic energy (ZEKE)
      photoelectron spectroscopy and density functional theory. The theory predicts two
      low-energy isomers: a clamshell structure with Sc binding to both phenyl rings
      and a half-sandwich structure with Sc binding to single ring. The joint
      experimental and theoretical study shows that the Sc(biphenyl) complex prefers
      the clamshell structure with a twelve-fold binding mode. From the free ligand to
      the clamshell structure of the complex, phenyl rings first rotate to become
      coplanar, then bend toward the Sc atom, and finally are clamped in place by Sc
      binding.

PMID- 16910660
TI  - The selective reaction of aryl halides with KOH: synthesis of phenols, aromatic
      ethers, and benzofurans.
AB  - The direct and selective synthesis of phenols from aryl/heteroaryl halides and
      KOH has been achieved through the use of highly active monophosphine-based
      catalysts derived from Pd(2)dba(3) and ligands L1 or L2 and the biphasic solvent
      system 1,4-dioxane/H(2)O. We have also demonstrated a one-pot method of phenol
      formation/alkylation for the preparation of alkyl aryl ethers from aryl halides.
      In many instances, this protocol overcomes limitations in existing Pd-catalyzed
      coupling reactions of aliphatic alcohols with aryl halides. Finally, we
      demonstrate that substituted benzofurans can be prepared efficiently via a Pd
      catalyzed phenol formation/cyclization protocol starting from 2-chloroaryl
      alkynes.

PMID- 16910661
TI  - N-C bond formation promoted by a hafnocene dinitrogen complex: comparison of
      zirconium and hafnium congeners.
AB  - Nitrogen-carbon bond formation from coordinated dinitrogen has been observed upon
      addition of 2 equiv of PhNCO to the hafnocene dinitrogen complex, [(eta5
      C5Me4H)2Hf]2(mu2,eta2,eta2-N2). The resulting product most likely arises from
      initial N=C cycloaddition of the first equivalent of heterocumulene, followed by
      carbonyl insertion of a second equivalent into the newly formed hafnium-nitrogen
      bond. The resulting product has considerable hafnium imido character, as
      evidenced by the metrical parameters determined from the solid-state structure as
      well as reactivity studies, whereby PhNCO, p-tolyl isocyanate, and t-BuCCH each
      undergo cycloaddition with the hafnium-nitrogen bond. The origin of the nitrogen
      carbon-forming chemistry is likely derived from the reluctance of the hafnocene
      dinitrogen complex to undergo ligand-induced N2 isomerization, as was observed
      with the zirconium congener.

PMID- 16910662
TI  - Characterization of the cereulide NRPS alpha-hydroxy acid specifying modules:
      activation of alpha-keto acids and chiral reduction on the assembly line.
AB  - Several nonribosomal peptide natural products are composites of alpha-hydroxy
      acid and alpha-amino acid monomers. Cereulide, the emetic toxin from the human
      pathogen Bacillus cereus, and valinomycin, from Streptomyces spp., are closely
      related macrocyclic K+ ionophores. The macrocyclic core of each natural product
      contains alternating peptide (six) and ester (six) bonds, and their
      cyclododecadepsipeptide structures consist of a tetradepsipeptide unit repeated
      three times. Here we overexpress the cereulide NRPS alpha-hydroxy acid specifying
      modules from CesA and CesB and demonstrate that each contains an alpha-keto acid
      activating adenylation domain and a chiral alpha-ketoacyl-S-carrier protein
      reductase (alpha-KR). The logic used by the cereulide NRPS is likely at work in
      the valinomycin NRPS and may be the general strategy used in bacterial NRPSs to
      form alpha-hydroxy acid containing natural products.

PMID- 16910663
TI  - Transferring self-assembled, nanoscale cables into electrical devices.
AB  - This study details a new derivative of the contorted HBCs that self-organizes
      into one-dimensional, single-crystalline fibers. X-ray diffraction, transmission
      electron microscopy, and electron diffraction studies show that they have an
      orthorhombic unit cell with dimensions of 5.8 nm x 4.5 nm x 0.45 nm. Each fiber
      is composed of a few thousands columns. A method is put forth that utilizes
      elastomer stamps to manipulate and position isolated fibers in organic field
      effect transistors.

PMID- 16910664
TI  - Can ring strain be realized in momentum space?
AB  - An increased electron momentum density (EMD) at low momentum is proposed to be an
      indicator of ring strain, with the nature of the function tending toward a
      maximum. A p-space Hirshfeld atomic partitioning scheme is applied for analyzing
      the effect of strain on molecular EMDs. The Hirshfeld momentum densities for a
      strained system show an increase in the population for the carbons with the
      hydrogens becoming more positive in comparison with an unstrained reference
      molecule. The manifestation of strain in cage-like hydrocarbons such as
      tetrahedrane, cubane, prismane, etc. as well as their nitrogen-substituted
      analogues is clearly seen in terms of EMDs.

PMID- 16910665
TI  - Supramolecular self-assembly of dendronized polymers: reversible control of the
      polymer architectures through acid-base reactions.
AB  - Acid-base switchable supramolecular dendronized polyacetylenes (DPAs) with
      increasing steric bulk on going from generation one [G1] to three [G3], were
      constructed using multiple self-assembly processes between Frechet-type [G1]-[G3]
      dendritic dialkylammonium salts and a dibenzo[24]crown-8-containing polymer. The
      formation of the supramolecular systems is acid-base switchable to either an ON
      (rodlike dendronized polymers) or an OFF (flexible polymers) state. Thus, by
      controlling the superstructures of the supramolecular polymers with the [G1]-[G3]
      dendrons, it is possible to induce conformational changes within the polymer
      backbones. The supramolecular dendronized polymers, as well as their threading
      dethreading properties, were characterized by (1)H NMR and UV absorption
      spectroscopies, gel permeation chromatography (GPC) and light scattering (LS).
      Independent measures of molecular weight (GPC, LS) indicate that DPAs behave as
      increasingly rigid macromolecules with each generation in solution. Molecular
      dynamics simulations of each DPA suggest that the lengths of the polymer
      backbones increase accordingly. Atomic force microscopy of the [G3]-dendronized
      polystyrene (DPS), as well as the DPAs, reveal surface morphologies indicative of
      aggregated superstructures.

PMID- 16910666
TI  - Simultaneous interaction with base and phosphate moieties modulates the
      phosphodiester cleavage of dinucleoside 3',5'-monophosphates by dinuclear Zn2+
      complexes of di(azacrown) ligands.
AB  - Five dinucleating ligands (1-5) and one trinucleating ligand (6) incorporating
      1,5,9-triazacyclododecan-3-yloxy groups attached to an aromatic scaffold have
      been synthesized. The ability of the Zn(2+) complexes of these ligands to promote
      the transesterification of dinucleoside 3',5'-monophosphates to a 2',3'-cyclic
      phosphate derived from the 3'-linked nucleoside by release of the 5'-linked
      nucleoside has been studied over a narrow pH range, from pH 5.8 to 7.2, at 90
      degrees C. The dinuclear complexes show marked base moiety selectivity. Among the
      four dinucleotide 3',5'-phosphates studied, viz. adenylyl-3',5'-adenosine (ApA),
      adenylyl-3',5'-uridine (ApU), uridylyl-3',5'-adenosine (UpA), and uridylyl-3',5'
      uridine (UpU), the dimers containing one uracil base (ApU and UpA) are cleaved up
      to 2 orders of magnitude more readily than those containing either two uracil
      bases (UpU) or two adenine bases (ApA). The trinuclear complex (6), however,
      cleaves UpU as readily as ApU and UpA, while the cleavage of ApA remains slow. UV
      spectrophotometric and (1)H NMR spectroscopic studies with one of the
      dinucleating ligands (3) verify binding to the bases of UpU and ApU at less than
      millimolar concentrations, while no interaction with the base moieties of ApA is
      observed. With ApU and UpA, one of the Zn(2+)-azacrown moieties in all likelihood
      anchors the cleaving agent to the uracil base of the substrate, while the other
      azacrown moiety serves as a catalyst for the phosphodiester transesterification.
      With UpU, two azacrown moieties are engaged in the base moiety binding. The
      catalytic activity is, hence, lost, but it can be restored by addition of a third
      azacrown group on the cleaving agent.

PMID- 16910667
TI  - 19F NMR studies of the native and denatured states of green fluorescent protein.
AB  - Biosynthetic preparation and (19)F NMR experiments on uniformly 3-fluorotyrosine
      labeled green fluorescent protein (GFP) are described. The (19)F NMR signals of
      all 10 fluorotyrosines are resolved in the protein spectrum with signals spread
      over 10 ppm. Each tyrosine in GFP was mutated in turn to phenylalanine. The
      spectra of the Tyr --> Phe mutants, in conjunction with relaxation data and
      results from (19)F photo-CIDNP (chemically induced dynamic nuclear polarization)
      experiments, yielded a full (19)F NMR assignment. Two (19)F-Tyr residues (Y92 and
      Y143) were found to yield pairs of signals originating from ring-flip conformers;
      these two residues must therefore be immobilized in the native structure and have
      (19)F nuclei in two magnetically distinct positions depending on the orientation
      of the aromatic ring. Photo-CIDNP experiments were undertaken to probe further
      the structure of the native and denatured states. The observed NMR signal
      enhancements were found to be consistent with calculations of the HOMO (highest
      occupied molecular orbital) accessibilities of the tyrosine residues. The photo
      CIDNP spectrum of native GFP shows four peaks corresponding to the four tyrosine
      residues that have solvent-exposed HOMOs. In contrast, the photo-CIDNP spectra of
      various denatured states of GFP show only two peaks corresponding to the (19)F
      labeled tyrosine side chains and the (19)F-labeled Y66 of the chromophore. These
      data suggest that the pH-denatured and GdnDCl-denatured states are similar in
      terms of the chemical environments of the tyrosine residues. Further analysis of
      the sign and amplitude of the photo-CIDNP effect, however, provided strong
      evidence that the denatured state at pH 2.9 has significantly different
      properties and appears to be heterogeneous, containing subensembles with
      significantly different rotational correlation times.

PMID- 16910668
TI  - Nucleophilic substitution at phosphorus (S(N)2@P): disappearance and reappearance
      of reaction barriers.
AB  - Pentacoordinate phosphorus species play a key role in organic and biological
      processes. Yet, their nature is still not fully understood, in particular,
      whether they are stable, intermediate transition complexes (TC) or labile
      transition states (TS). Through systematic, theoretical analyses of elementary
      S(N)2@C, S(N)2@Si, and S(N)2@P reactions, we show how increasing the coordination
      number of the central atom as well as the substituents' steric demand shifts the
      S(N)2@P mechanism stepwise from a single-well potential (with a stable central
      TC) that is common for substitution at third-period atoms, via a triple-well
      potential (featuring a pre- and post-TS before and after the central TC), back to
      the double-well potential (in which pre- and postbarrier merge into one central
      TS) that is well-known for substitution reactions at carbon. Our results
      highlight the steric nature of the S(N)2 barrier, but they also show how
      electronic effects modulate the barrier height.

PMID- 16910669
TI  - A porous framework polymer based on a zinc(II) 4,4'-bipyridine-2,6,2',6'
      tetracarboxylate: synthesis, structure, and "zeolite-like" behaviors.
AB  - The robust metal-organic framework compound {[Zn(2)(L)] x 4H(2)O}(infinity) I has
      been synthesized by hydrothermal reaction of ZnCl(2) and 4,4'-bipyridine
      2,6,2',6'-tetracarboxylic acid (H(4)L). Compound I crystallizes in a chiral space
      group, P4(2)2(1)2, with the chirality generated by the helical chains of hydrogen
      bonded guest water molecules rather than by the coordination framework. Removal
      of guest water molecules from the crystal affords the porous material,
      [Zn(2)(L)](infinity) (II), which has very high thermal stability and is
      chemically inert. The N(2) isotherm of II at 77 K suggests a uniform porous
      structure with a BET surface area of 312.7 m(2)/g and a remarkably strong
      interaction with N(2) molecules (betaE(0) = 29.6 kJ mol(-)(1)). II also exhibits
      significant gas storage capacities of 1.08 wt % for H(2) at 4 bar and 77 K and
      3.14 wt % (44.0 cm(3)/g, 67 v/v) for methane at 9 Bar at 298 K. The adsorption
      behavior of II toward organic solvent vapors has also been studied, and isotherms
      reveal that for different solvent vapors adsorption is dominated by two types of
      processes, absorbate-absorbate or absorbate-absorbent interactions. The
      adsorption and desorption kinetic processes in II are determined mainly by the
      molecular size of the guest species and their interaction with the host.

PMID- 16910670
TI  - Ratiometric fluorescent sensor proteins with subnanomolar affinity for Zn(II)
      based on copper chaperone domains.
AB  - The ability to image the concentration of transition metals in living cells in
      real time is important for further understanding of transition metal homeostasis
      and its involvement in diseases. The goal of this study was to develop a
      genetically encoded FRET-based sensor for copper(I) based on the copper-induced
      dimerization of two copper binding domains involved in human copper homeostasis,
      Atox1 and the fourth domain of ATP7B (WD4). A sensor has been constructed by
      linking these copper binding domains to donor and acceptor fluorescent protein
      domains. Energy transfer is observed in the presence of Cu(I), but the Cu(I)
      bridged complex is easily disrupted by low molecular weight thiols such as DTT
      and glutathione. To our surprise, energy transfer is also observed in the
      presence of very low concentrations of Zn(II) (10(-)(10) M), even in the presence
      of DTT. Zn(II) is able to form a stable complex by binding to the cysteines
      present in the conserved MXCXXC motif of the two copper binding domains. Co(II),
      Cd(II), and Pb(II) also induce an increase in FRET, but other, physiologically
      relevant metals are not able to mediate an interaction. The Zn(II) binding
      properties have been tuned by mutation of the copper-binding motif to the zinc
      binding consensus sequence MDCXXC found in the zinc transporter ZntA. The present
      system allows the molecular mechanism of copper and zinc homeostasis to be
      studied under carefully controlled conditions in solution. It also provides an
      attractive platform for the further development of genetically encoded FRET-based
      sensors for Zn(II) and other transition metal ions.

PMID- 16910671
TI  - Cationic oligonucleotide-peptide conjugates with aggregating properties enter
      efficiently into cells while maintaining hybridization properties and enzymatic
      recognition.
AB  - Oligonucleotide delivery is a crucial issue for therapeutical purposes and is
      often addressed by conjugation to short cationic peptides although with
      controversial results. To further examine this mechanism, a 15-mer anionic
      oligonucleotide was conjugated to a cationic peptide in order to obtain a diblock
      compound with an overall positive charge with aggregation properties. These
      microaggregates were efficiently internalized in cells via the expeditious
      pathway used by commercial gene delivery systems. Moreover, stability of the
      duplex formed with the complementary sequence increased without inhibiting
      oligonucleotide enzyme recognition as shown by the properties of the conjugate to
      prime chain elongation by Taq DNA polymerase in a linear amplification/sequencing
      process.

PMID- 16910672
TI  - A combined experimental and theoretical study of the kinetics and mechanism of
      the addition of alcohols to electronically stabilized silenes: a new mechanism
      for the addition of alcohols to the Si=C bond.
AB  - The stabilized silene 1,1-bis(trimethylsilyl)-2-adamantylidenesilane (4) has been
      generated by photolysis of a novel trisilacyclobutane derivative in various
      solvents and studied directly by kinetic UV spectrophotometry. Silene 4 decays
      with second-order kinetics in degassed hexane solution at 23 degrees C (k/epsilon
      = 8.6 x 10(-6) cm s(-1)) due to head-to-head dimerization. It reacts rapidly with
      oxygen [k(25 degrees C) approximately 3 x 10(5) M(-1) s(-1)] but approximately 10
      orders of magnitude more slowly with methanol (MeOH) than other silenes that have
      been studied previously. The data are consistent with a mechanism involving
      reaction with the hydrogen-bonded dimer of the alcohol, (MeOH)(2) (k = 40 +/- 3
      M(-1) s(-1); k(H)/k(D) = 1.7 +/- 0.2). The stable analogue of silene 4, 1-tert
      butyldimethylsilyl-1-trimethylsilyl-2-adamantylidenesilane (5), reacts
      approximately 50 times more slowly, but via the same mechanism. The mechanism for
      addition of water and methanol (ROH; R = H, Me) to 4, 5, and the model compound
      1,1-bis(silyl)-2,2-dimethylsilene (3a) has been studied computationally at the
      B3LYP/6-31G(d) and MP2/6-31G(d) levels of theory. Hydrogen-bonded complexes with
      monomeric and dimeric methanol, in which the Si=C bond plays the role of
      nucleophile, have been located computationally for all three silenes. Reaction
      pathways have been characterized for reaction of the three silenes with monomeric
      and dimeric ROH and reveal significantly lower barriers for reaction with the
      dimeric form of the alcohol in each case. The calculations indicate that 5 should
      be approximately 40-fold less reactive toward dimeric MeOH than 4, in excellent
      agreement with the approximately 50-fold difference in the experimental rate
      constants for reaction in hexane solution.

PMID- 16910673
TI  - A fluoro analogue of the menadione derivative 6-[2'-(3'-methyl)-1',4'
      naphthoquinolyl]hexanoic acid is a suicide substrate of glutathione reductase.
      Crystal structure of the alkylated human enzyme.
AB  - Glutathione reductase is an important housekeeping enzyme for redox homeostasis
      both in human cells and in the causative agent of tropical malaria, Plasmodium
      falciparum. Glutathione reductase inhibitors were shown to have anticancer and
      antimalarial activity per se and to contribute to the reversal of drug
      resistance. The development of menadione chemistry has led to the selection of 6
      [2'-(3'-methyl)-1',4'-naphthoquinolyl]hexanoic acid, called M(5), as a potent
      reversible and uncompetitive inhibitor of both human and P. falciparum
      glutathione reductases. Here we describe the synthesis and kinetic
      characterization of a fluoromethyl-M(5) analogue that acts as a mechanism-based
      inhibitor of both enzymes. In the course of enzymatic catalysis, the suicide
      substrate is activated by one- or two-electron reduction, and then a highly
      reactive quinone methide is generated upon elimination of the fluorine.
      Accordingly the human enzyme was found to be irreversibly inactivated with a
      k(inact) value of 0.4 +/- 0.2 min(-1). The crystal structure of the alkylated
      enzyme was solved at 1.7 A resolution. It showed the inhibitor to bind covalently
      to the active site Cys58 and to interact noncovalently with His467', Arg347,
      Arg37, and Tyr114. On the basis of the crystal structure of the inactivated human
      enzyme and stopped-flow kinetic studies with two- and four-electron-reduced forms
      of the unreacted P. falciparum enzyme, a mechanism is proposed which explains
      naphthoquinone reduction at the flavin of glutathione reductase.

PMID- 16910674
TI  - Oxidative damage to DNA: counterion-assisted addition of water to ionized DNA.
AB  - Oxidative damage to DNA, implicated in mutagenesis, aging, and cancer, follows
      electron loss that generates a radical cation that migrates to a guanine, where
      it may react with water to form 8-oxo-7,8-dihydroguanine (8-OxoG). Molecular
      dynamics and ab initio quantum simulations on a B-DNA tetradecamer reveal
      activated reaction pathways that depend on the local counterion arrangement. The
      lowest activation barrier, 0.73 eV, is found for a reaction that starts from a
      configuration where a Na(+) resides in the major groove near the N7 atoms of
      adjacent guanines, and evolves through a transition state where a bond between a
      water oxygen atom and a carbon atom forms concurrently with displacement of a
      proton toward a neighboring water molecule. Subsequently, a bonded complex of a
      hydronium ion and the nearest backbone phosphate group forms. This counterion
      assisted proton shuttle mechanism is supported by experiments exploiting
      selective substitution of backbone phosphates by methylphosphonates.

PMID- 16910675
TI  - Physical controls on directed virus assembly at nanoscale chemical templates.
AB  - Viruses are attractive building blocks for nanoscale heterostructures, but little
      is understood about the physical principles governing their directed assembly. In
      situ force microscopy was used to investigate organization of Cowpea Mosaic Virus
      engineered to bind specifically and reversibly at nanoscale chemical templates
      with sub-30 nm features. Morphological evolution and assembly kinetics were
      measured as virus flux and inter-viral potential were varied. The resulting
      morphologies were similar to those of atomic-scale epitaxial systems, but the
      underlying thermodynamics was analogous to that of colloidal systems in confined
      geometries. The 1D templates biased the location of initial cluster formation,
      introduced asymmetric sticking probabilities, and drove 1D and 2D condensation at
      sub-critical volume fractions. The growth kinetics followed a t(1/2) law
      controlled by the slow diffusion of viruses. The ability of poly(ethylene glycol)
      (PEG) to induce the lateral expansion of virus clusters away from the 1D
      templates suggests a significant role for weak interactions.

PMID- 16910676
TI  - Color tuning in rhodopsins: the mechanism for the spectral shift between
      bacteriorhodopsin and sensory rhodopsin II.
AB  - The mechanism of color tuning in the rhodopsin family of proteins has been
      studied by comparing the optical properties of the light-driven proton pump
      bacteriorhodopsin (bR) and the light detector sensory rhodopsin II (sRII).
      Despite a high structural similarity, the maximal absorption is blue-shifted from
      568 nm in bR to 497 nm in sRII. The molecular mechanism of this shift is still a
      matter of debate, and its clarification sheds light onto the general mechanisms
      of color tuning in retinal proteins. The calculations employ a combined quantum
      mechanical/molecular mechanical (QM/MM) technique, using a DFT-based method for
      ground state properties and the semiempirical OM2/MRCI method and ab initio SORCI
      method for excited state calculations. The high efficiency of the methodology has
      allowed us to study a wide variety of aspects including dynamical effects. The
      absorption shift as well as various mutation experiments and vibrational
      properties have been successfully reproduced. Our results indicate that several
      sources contribute to the spectral shift between bR and sRII. The main factors
      are the counterion region at the extracellular side of retinal and the amino acid
      composition of the binding pocket. Our analysis allows a distinction and
      identification of the different effects in detail and leads to a clear picture of
      the mechanism of color tuning, which is in good agreement with available
      experimental data.

PMID- 16910677
TI  - Electrochemical, spectroelectrochemical, and molecular quadratic and cubic
      nonlinear optical properties of alkynylruthenium dendrimers.
AB  - A combination of cyclic voltammetry (CV), UV-vis-NIR spectroscopy and
      spectroelectrochemistry, hyper-Rayleigh scattering (HRS) [including
      depolarization studies], Z-scan and degenerate four-wave mixing (DFWM) [including
      studies employing an optically transparent thin-layer electrochemical (OTTLE)
      cell to effect electrochemical switching of nonlinearity], pump-probe, and
      electroabsorption (EA) measurements have been used to comprehensively investigate
      the electronic, linear optical, and nonlinear optical (NLO) properties of
      nanoscopic pi-delocalizable electron-rich alkynylruthenium dendrimers, their
      precursor dendrons, and their linear analogues. CV, UV-vis-NIR spectroscopy, and
      UV-vis-NIR spectroelectrochemistry reveal that the reversible metal-centered
      oxidation processes in these complexes are accompanied by strong linear optical
      changes, "switching on" low-energy absorption bands, the frequency of which is
      tunable by ligand replacement. HRS studies at 1064 nm employing nanosecond pulses
      reveal large nonlinearities for these formally octupolar dendrimers;
      depolarization measurements are consistent with lack of coplanarity upon pi
      framework extension through the metal. EA studies at 350-800 nm in a poly(methyl
      methacrylate) matrix are consistent with the important transitions having a
      charge-transfer exciton character that increases markedly on introduction of
      peripheral polarizing substituent. Time-resolved pump-probe studies employing 55
      ps, 527 nm pulses reveal absorption saturation, the longest excited-state
      lifetime being observed for the dendrimer. Z-scan studies at 800 nm employing
      femtosecond pulses reveal strong two-photon absorption that increases
      significantly on progression from linear complex to zero- and then first
      generation dendrimer with no loss of optical transparency. Both refractive and
      absorptive nonlinearity for selected alkynylruthenium dendrimers have been
      reversibly "switched" by employing the Z-scan technique at 800 and 1180 nm and
      100-150 fs pulses, together with a specially modified OTTLE cell, complementary
      femtosecond time-resolved DFWM and transient absorption studies at 800 nm
      suggesting that the NLO effects originate in picosecond time scale processes.

PMID- 16910678
TI  - Chirally directed formation of nanometer-scale proline clusters.
AB  - Ion mobility measurements, combined with molecular mechanics simulations, are
      used to study enantiopure and racemic proline clusters formed by electrospray
      ionization. Broad distributions of cluster sizes and charge states are observed,
      ranging from clusters containing only a few proline units to clusters that
      contain more than 100 proline units (i.e., protonated clusters of the form [xPro
      + nH](n+) with x = 1 to >100 and n = 1-7). As the sizes of clusters increase,
      there is direct evidence for nanometer scale, chirally induced organization into
      specific structures. For n = 4 and 5, enantiopure clusters of approximately 50 to
      100 prolines assemble into structures that are more elongated than the most
      compact structure that is observed from the racemic proline clusters. A molecular
      analogue, cis-4-hydroxy-proline, displays significantly different behavior,
      indicating that in addition to the rigidity of the side chain ring,
      intermolecular interactions are important in the formation of chirally directed
      clusters. This is the first case in which assemblies of chirally selective
      elongated structures are observed in this size range of amino acid clusters.
      Relationships between enantiopurity, cluster shape, and overall energetics are
      discussed.

PMID- 16910679
TI  - Dynamic nuclear polarization of amyloidogenic peptide nanocrystals: GNNQQNY, a
      core segment of the yeast prion protein Sup35p.
AB  - Dynamic nuclear polarization (DNP) permits a approximately 10(2)-10(3)
      enhancement of the nuclear spin polarization and therefore increases sensitivity
      in nuclear magnetic resonance (NMR) experiments. Here, we demonstrate the
      efficient transfer of DNP-enhanced (1)H polarization from an aqueous, radical
      containing solvent matrix into peptide crystals via (1)H-(1)H spin diffusion
      across the matrix-crystal interface. The samples consist of nanocrystals of the
      amyloid-forming peptide GNNQQNY(7-13), derived from the yeast prion protein
      Sup35p, dispersed in a glycerol-water matrix containing a biradical polarizing
      agent, TOTAPOL. These crystals have an average width of 100-200 nm, and their
      known crystal structure suggests that the size of the biradical precludes its
      penetration into the crystal lattice; therefore, intimate contact of the
      molecules in the nanocrystal core with the polarizing agent is unlikely. This is
      supported by the observed differences between the time-dependent growth of the
      enhanced polarization in the solvent versus the nanocrystals. Nevertheless, DNP
      enhanced magic-angle spinning (MAS) spectra recorded at 5 T and 90 K exhibit an
      average signal enhancement epsilon approximately 120. This is slightly lower than
      the DNP enhancement of the solvent mixture surrounding the crystals (epsilon
      approximately 160), and we show that it is consistent with spin diffusion across
      the solvent-matrix interface. In particular, we correlate the expected DNP
      enhancement to several properties of the sample, such as crystal size, the
      nuclear T(1), and the average (1)H-(1)H spin diffusion constant. The enhanced
      (1)H polarization was subsequently transferred to (13)C and (15)N via cross
      polarization, and allowed rapid acquisition of two-dimensional (13)C-(13)C
      correlation data.

PMID- 16910680
TI  - Crystal structure of homo-DNA and nature's choice of pentose over hexose in the
      genetic system.
AB  - An experimental rationalization of the structure type encountered in DNA and RNA
      by systematically investigating the chemical and physical properties of
      alternative nucleic acids has identified systems with a variety of sugar
      phosphate backbones that are capable of Watson-Crick base pairing and in some
      cases cross-pairing with the natural nucleic acids. The earliest among the model
      systems tested to date, (4' --> 6')-linked oligo(2',3'-dideoxy-beta-d
      glucopyranosyl)nucleotides or homo-DNA, shows stable self-pairing, but the
      pairing rules for the four natural bases are not the same as those in DNA.
      However, a complete interpretation and understanding of the properties of the
      hexapyranosyl (4' --> 6') family of nucleic acids has been impeded until now by
      the lack of detailed 3D-structural data. We have determined the crystal structure
      of a homo-DNA octamer. It reveals a weakly twisted right-handed duplex with a
      strong inclination between the hexose-phosphate backbones and base-pair axes, and
      highly irregular values for helical rise and twist at individual base steps. The
      structure allows a rationalization of the inability of allo-, altro-, and
      glucopyranosyl-based oligonucleotides to form stable pairing systems.

PMID- 16910681
TI  - Structural features of the modulated BiCu2(P(1-x)V(x))O6 solid solution; 4-D
      treatment of x = 0.87 compound and magnetic spin-gap to gapless transition in new
      Cu2+ two-leg ladder systems.
AB  - The BiCu(2)(P(1-x)V(x))O(6) system shows the appearance of various phenomena that
      progressively change as a function of the average (P/V)O(4) groups size. Then,
      from x = 0 to x approximately 0.7, a solid solution exists with respect to the
      basic orthorhombic unit cell of BiCu(2)PO(6). For greater x values (0.7 < x
      <0.96), structural modulations with incommensurate q vector that slightly change
      versus x appear. The 4-D treatment of single-crystal XRD data of the modulated
      phase corresponding to x = 0.87 at 100 K (orthorhombic, a = 12.379(3)Angstrom, b
      = 5.2344(9) Angstrom, c = 7.8270(14) Angstrom, q = 0.268(3) b*, super space
      group: Xbmm(0gamma0) s00, X stands for the nonprimitive centering vector
      (1/2,0,1/2,1/2), R(obs)(overall) = 5.27%, R(obs)(fundamental) = 4.48%,
      R(obs)(satellite) = 6.58%) has evidenced strong positional modulated effects
      within the [BiCu(2)O(2)](3+) ribbons while three XO(4) configurations compete
      along the x(4) fourth dimension. There is no P/V segregation along x(4) in good
      agreement with steric-only origins of the modulation. Finally for 0.96 < x <1,
      two phases coexist, i.e., BiCu(2)VO(6) (X = 1) and a modulated phase of the
      previous domain.The BiCu(2)VO(6) crystal structure shows a unit cell tripling
      associated with monoclinic symmetry lowering. The VO(4) orientations between two
      ribbons proceed with respect to the interribbon distance. Then the full system
      shows flexible interactions between modulated Bi/M/O-based ribbons and
      surrounding tetrahedral groups, depending on the average XO(4) size. Furthermore,
      between two ribbons the Cu(2+) arrangement forms magnetically isolated zigzag
      copper two-leg ladders. Our preliminary results show a spin-gap behavior likely
      due to the existence of true S = (1)/(2) Heisenberg two-leg ladders. Modulated
      compositions are gapless, in good agreement with band-broadening toward a
      continuum in the magnetic excitation spectrum. The continuous distribution of Cu
      Cu distances along the rungs and legs of the ladders should be mainly responsible
      for this magnetic change.

PMID- 16910682
TI  - Rapid energy transfer in cascade-type bodipy dyes.
AB  - Three new molecular dyads, comprising a bora-3a,4a-diaza-s-indacene (Bodipy) dye
      linked to two aromatic polycycles via the boron center, have been synthesized and
      fully characterized. The polycyclic compounds are either pyrene or perylene, or a
      mixture of both. Whereas the absorption spectral profiles contain important
      contributions from each of the subunits, fluorescence occurs exclusively from the
      Bodipy fragment. Intramolecular excitation energy transfer is extremely efficient
      in each case, even though spectral overlap integrals for the pyrene-based system
      are modest. Although these polycycles are sterically congested, molecular
      dynamics simulations indicate that they are in dynamic motion, and this hinders
      proper computation of the orientation factors for Forster-type energy transfer.
      These new dyes, especially the mixed polycycle system, greatly extend the range
      of excitation wavelengths that can be used for fluorescence microscopy.

PMID- 16910683
TI  - Molecular dynamics simulations on the Escherichia coli ammonia channel protein
      AmtB: mechanism of ammonia/ammonium transport.
AB  - Molecular dynamics (MD) simulations have been performed at the atomic level to
      study the ammonium/ammonia transport across the Escherichia coli AmtB membrane
      protein. Although ammonia primarily exists in the form of NH(4)(+) in aqueous
      solution, the recent X-ray structure determination of AmtB reveals that the
      ammonium/ammonia transporter proteins are ammonia-conducting channels rather than
      ammonium ion transporters [Khademi, S.; et al. Science 2004, 305, 1587; Zheng,
      L.; et al. Proc. Natl. Acad. Sci. U.S.A. 2004, 101, 17090]. Our simulations
      showed that the entrance of NH(4)(+) into the periplasmic recruitment vestibule
      requires only 3.1 kcal/mol of energy. This is consistent with the X-ray crystal
      structure, where one NH(4)(+) is captured in the binding vestibule. In this
      vestibule, NH(4)(+) loses one water of hydration, but the loss is compensated by
      a hydrogen bond, first with the backbone carbonyl oxygen of Phe161 then with the
      hydroxyl group of Ser219, as well as the stabilizing pi-cation interactions with
      the aromatic rings of Trp148 and Phe107 in the AmtB protein. In the end of this
      recruitment vestibule, the phenyl ring of Phe107 dynamically switches to an open
      state. This is correlated with a slight rotation and shifting of the indole ring
      of Trp148, which eventually creates a slot for the initially buried carboxylate
      group of Asp160 to become exposed to the bulk solvent. A hydrogen bond wire
      between NH(4)(+) and the carboxylate group of Asp160 via two water molecules was
      observed. Thus, Asp160 is most likely the proton acceptor from NH(4)(+). This
      explains the high conservation of Asp160 in Amt proteins and why the D160A mutant
      would completely quench the activity of AmtB [Javelle, A.; et al. J. Biol. Chem.
      2004, 279, 8530; Marini, A. M.; et al. Curr. Genet. 2006, 49, 364]. Once NH(4)(+)
      deprotonates, the phenyl ring of Phe215 rotates to open, and the subsequent
      passage of NH(3) through the channel is straightforward.

PMID- 16910684
TI  - Triphenylene analogues with B2N2C2 cores: synthesis, structure, redox behavior,
      and photophysical properties.
AB  - A series of alkyl (1-3), aryl (6), and benzo-annulated (4, 5) heteroaromatic
      triphenylene analogues with B(2)N(2)C(2) cores have been synthesized via
      chelation of pyridazine derivatives using difunctional Lewis acidic
      diborabiphenyl precursors. In contrast to triphenylene, NICS(1) calculations on 1
      suggested high aromaticities for the central (-11.3 ppm) and outer borabenzene
      rings (-7.7 ppm), along with nonaromatic behavior for the pyridazine ring (-0.7
      ppm). Crystal structure analyses supported this analysis. When the a- and c-faces
      of the pyridazine moiety were free of substitution (1, 3), planar structures
      resulted, but upon substitution, a twisted B(2)N(2)C(2) core was observed due to
      steric repulsion of neighboring hydrogen atoms (e.g., 5). The increase of steric
      bulk from H (1) to (i)Pr (3) in the planar species was found to result in a
      dimeric, head-to-tail herringbone packing motif, held together by close
      intermolecular B...N interactions of 3.39 Angstrom. One-electron reduction by
      Cp(2)Co was found to afford the radical anions of 3 and 5, which were
      characterized by broad, featureless singlets in the EPR spectra; [3](.)(
      )[Cp(2)Co](+) was characterized by X-ray crystallography. While the planar
      structures (1-4) were observed to possess weak fluorescence (Phi(F) = 0.02-0.08)
      with either yellow-orange (ca. 555 nm) or green emission (521 nm), the twisted
      structures (5, 6) were found to be nonfluorescent.

PMID- 16910685
TI  - Microwave-assisted self-organization of colloidal particles in confining aqueous
      droplets.
AB  - Monodisperse aqueous emulsion droplets encapsulating colloidal particles were
      produced in the oil phase, and controlled microwave irradiation of the aqueous
      drop phase created spherical colloidal crystals by so-called evaporation-induced
      self-organization of the colloidal particles. Unlike usual colloidal crystals,
      colloidal crystals in spherical symmetry (or photonic balls) possessed photonic
      band gaps for the normal incident light independent of the position all over the
      spherical surface. While the consolidation of colloidal particles in emulsion
      droplets in an oven took several hours, the present microwave-assisted
      evaporation could reduce the time for complete evaporation to a few tens of
      minutes. Under the microwave irradiation, the aqueous phase in emulsions was
      superheated selectively and the evaporation rate of water could be controlled
      easily by adjusting the microwave intensity. The result showed that the packing
      quality of colloidal crystals obtained by the microwave-assisted self
      organization was good enough to show photonic band gap characteristics. The
      reflectance of our photonic balls responded precisely to any change in physical
      properties including the size of colloidal particles, refractive index mismatch,
      and angle of the incident beam. In particular, for polymeric particles, the
      photonic band gap could be tuned by the intensity of microwave irradiation, and
      the reflection color was red-shifted with stronger microwave irradiation.
      Finally, for better photonic band gap properties, inverted photonic balls were
      prepared by using the spherical colloidal crystals as sacrificial templates.

PMID- 16910686
TI  - Localized surface plasmon resonance spectroscopy near molecular resonances.
AB  - The peak location of the localized surface plasmon resonance (LSPR) of noble
      metal nanoparticles is highly dependent upon the refractive index of the
      nanoparticles' surrounding environment. In this study, new phenomena are revealed
      by exploring the influence of interacting molecular resonances and nanoparticle
      resonances. The LSPR peak shift and line shape induced by a resonant molecule
      vary with wavelength. In most instances, the oscillatory dependence of the peak
      shift on wavelength tracks with the wavelength dependence of the real part of the
      refractive index, as determined by a Kramers-Kronig transformation of the
      molecular resonance absorption spectrum. A quantitative assessment of this shift
      based on discrete dipole approximation calculations shows that the Kramers-Kronig
      index must be scaled in order to match experiment.

PMID- 16910687
TI  - Reversal of stability on metalation of pentagonal-bipyramidal (1-MB6H7(2-) 1-M-2
      CB5H7(1-) and 1-M-2,4-C2B4H7) and Icosahedral (1-MB11H12(2-) 1-M-2-CB10H12(1-)
      and 1-M-2,4-C2B9H12) boranes (M = Al, Ga, In, and Tl): energetics of condensation
      and relationship to binuclear metallocenes.
AB  - The usual assumption of the extra stability of icosahedral boranes (2) over
      pentagonal-bipyramidal boranes (1) is reversed by substitution of a vertex by a
      group 13 metal. This preference is a result of the geometrical requirements for
      optimum overlap between the five-membered face of the ligand and the metal
      fragment. Isodesmic equations calculated at the B3LYP/LANL2DZ level indicate that
      the extra stability of 1-M-2,4-C(2)B(4)H(7) varies from 14.44 kcal/mol (M = Al)
      to 15.30 kcal/mol (M = Tl). Similarly, M(2,4-C(2)B(4)H(6))(2)(1-) is more stable
      than M(2,4-C(2)B(9)H(11))(2)(1-) by 9.26 kcal/mol (M = Al) and by 6.75 kcal/mol
      (M = Tl). The preference for (MC(2)B(4)H(6))(2) over (MC(2)B(9)H(11))(2) at the
      same level is 30.54 kcal/mol (M = Al), 33.16 kcal/ mol (M = Ga) and 37.77
      kcal/mol (M = In). The metal-metal bonding here is comparable to those in CpZn
      ZnCp and H(2)M-MH(2) (M= Al, Ga, and In).

PMID- 16910688
TI  - Creation of a broad-range and highly stereoselective D-amino acid dehydrogenase
      for the one-step synthesis of D-amino acids.
AB  - Using both rational and random mutagenesis, we have created the first known broad
      substrate range, nicotinamide cofactor dependent, and highly stereoselective d
      amino acid dehydrogenase. This new enzyme is capable of producing d-amino acids
      via the reductive amination of the corresponding 2-keto acid with ammonia. This
      biocatalyst was the result of three rounds of mutagenesis and screening performed
      on the enzyme meso-diaminopimelate d-dehydrogenase. The first round targeted the
      active site of the wild-type enzyme and produced mutants that were no longer
      strictly dependent on the native substrate. The second and third rounds produced
      mutants that had an increased substrate range including straight- and branched
      aliphatic amino acids and aromatic amino acids. The very high selectivity toward
      the d-enantiomer (95 to >99% ee) was shown to be preserved even after the
      addition of the five mutations found in the three rounds of mutagenesis and
      screening. This new enzyme could complement and improve upon current methods for
      d-amino acid synthesis.

PMID- 16910689
TI  - Palladium-catalyzed C-H homocoupling of bromothiophene derivatives and synthetic
      application to well-defined oligothiophenes.
AB  - Synthesis of oligothiophenes of well-defined structures that possess 2-8
      thiophene units is performed with a new synthetic strategy involving C-H
      homocoupling of bromothiophenes and cross-coupling with organostannanes.
      Tolerance of the carbon-bromine bond to the palladium-catalyzed C-H homocoupling
      results in oligothiophenes bearing C-Br bonds at the terminal thiophene rings,
      which allow further transformation by the catalysis of a transition-metal
      complex.

PMID- 16910690
TI  - Photoinduced reductive repair of thymine glycol: implications for excess electron
      transfer through DNA containing modified bases.
AB  - Photoinduced reduction of thymine glycol in oligodeoxynucleotides was
      investigated using either a reduced form of flavin adenine dinucleotide (FADH(-))
      as an intermolecular electron donor or covalently linked phenothiazine (PTZ) as
      an intramolecular electron donor. Intermolecular electron donation from
      photoexcited flavin (FADH(-)) to free thymidine glycol generated thymidine in
      high yield, along with a small amount of 6-hydroxy-5,6-dihydrothymidine. In the
      case of photoreduction of 4-mer long single-stranded oligodeoxynucleotides
      containing thymine glycol by *FADH(-), the restoration yield of thymine was
      varied depending on the sequence of oligodeoxynucleotides. Time-resolved
      spectroscopic study on the photoreduction by laser-excited N,N-dimethylaniline
      (DMA) suggested elimination of a hydroxyl ion from the radical anion of thymidine
      glycol with a rate constant of approximately 10(4) s(-1) generates 6-hydroxy-5,6
      dihydrothymidine (6-HOT(*)) as a key intermediate, followed by further reduction
      of 6-HOT(*) to thymidine or 6-hydroxy-5,6-dihydrothymdine (6-HOT). On the other
      hand, an excess electron injected into double-stranded DNA containing thymine
      glycol was not trapped at the lesion but was further transported along the
      duplex. Considering redox properties of the nucleobases and PTZ, competitive
      excess electron trapping at pyrimidine bases (thymine, T and cytosine, C) which
      leads to protonation of the radical anion (T(-)(*), C(-)(*)) or rapid back
      electron transfer to the radical cation of PTZ (PTZ(+)(*)), is presumably faster
      than elimination of the hydroxyl ion from the radical anion of thymine glycol in
      DNA.

PMID- 16910691
TI  - Dynamic thermodynamic and dynamic kinetic resolution of 2-lithiopyrrolidines.
AB  - Dynamic resolution has been studied as a method for the asymmetric synthesis of 2
      substituted pyrrolidines. Highly enantioselective electrophilic substitutions of
      racemic 2-lithiopyrrolidines in the presence of a chiral ligand have been
      achieved. The organolithium compounds were prepared by tin-lithium exchange from
      the corresponding tributylstannanes and n-butyllithium or by deprotonation of N
      (tert-butyloxycarbonyl)pyrrolidine with sec-butyllithium. A range of N
      substituents and chiral ligands were investigated for the dynamic resolution.
      Electrophilic quench of the resolved diastereomeric 2-lithiopyrrolidine-chiral
      ligand complexes provided the enantiomerically enriched 2-substituted
      pyrrolidines. With N-alkyl derivatives, the resolution occurs conveniently at (or
      just below) room temperature and either enantiomer of the product can be formed
      by appropriate choice of the chiral ligand. The asymmetric induction occurs as a
      result of a thermodynamic preference for one of the diastereomeric complexes. The
      minor complex was found to have a faster rate of reaction with the electrophile.
      The use of N-allylic derivatives provides a means to prepare the N-unsubstituted
      pyrrolidine products. Best results were obtained with the N-2,3-dimethylbut-2
      enyl derivative, and this N-substituent could be cleaved using 1-chloroethyl
      chloroformate. With N-Boc-2-lithiopyrrolidine, the enantioselectivity arises by a
      kinetic resolution and high levels of asymmetric induction in the presence of
      excess n-butyllithium can be obtained. Dynamic kinetic resolution of the N-Boc
      derivative is limited in the scope of electrophile that can be used.

PMID- 16910692
TI  - Dynamic properties of metallocenium ion pairs in solution by atomistic
      simulations.
AB  - We report a molecular dynamics study of the dynamics and energetic of the
      [H(2)Si(Cp)(2)ZrMe(+)][MeB(C(6)F(5))(3)(-)], IP1, and
      [Me(2)Si(Cp)(2)ZrMe(+)][B(C(6)F(5))(4)(-)], IP2, ion pairs in benzene. The
      metrical parameters obtained for the IP1 ion pair are in excellent agreement with
      the NMR data reported for the strictly related
      [Me(2)Si(Cp)(2)ZrMe(+)][MeB(C(6)F(5))(3)(-)] ion pair (J. Am. Chem. Soc. 2004,
      126, 1448). This validates the molecular modeling protocol we developed.
      Simulation of the IP2 ion pair suggests that the counterion oscillates between
      two geometries characterized by a different coordination pattern of the F atoms
      to the Zr cation. In one case the B(C(6)F(5))(4)(-) coordinates to the metal with
      two F atoms of the same aryl ring, whereas in the other case two F atoms of
      different aryl rings are involved in the coordination. Strong solvent
      reorganization occurs around IP1 and IP2, as well as around the two isolated
      cations. In the case of the two ion pairs solvent is never coordinated directly
      to the metal, whereas in the absence of the counterion one benzene molecule is
      coordinated to the metal through a cation-pi interaction. Free energy
      calculations result in ion pair free energies of separation of 36.8 and 23.3
      kcal/mol for IP1 and IP2, respectively. Simulations with the Zr-B distance fixed
      at values > 7 A have been also performed. This mimics the situation occurring
      after counterion displacement by an inserting monomer molecule during olefin
      polymerization by the title catalysts.

PMID- 16910693
TI  - Site-specific nucleation and growth kinetics in hierarchical nanosyntheses of
      branched ZnO crystallites.
AB  - Here we report a site-specific sequential nucleation and growth route to the
      systematic building of hierarchical, complex, and oriented ZnO
      micro/nanostructures in solution nanosynthesis. Structures and morphologies of
      the products were confirmed by results from X-ray diffraction and scanning
      electron microscopy studies. The organic structure-directing agents (SDAs),
      diaminopropane and citrate, are found to play different roles in controlling the
      evolution of these new morphologies. Through the selective adsorptions of SDAs on
      different crystal facets of the primary ZnO rods, we have alternated the
      hierarchical growth of secondary and tertiary new complex nanostructures. Roles
      of the SDA concentration, nucleation time, and growth kinetics in the solution
      hierarchical ZnO nanosyntheses have all been systematically investigated.

PMID- 16910694
TI  - Synthesis and characterization of the octahydrotriborate complexes Cp*V(B3H8)2
      and Cp*Cr(B3H8)2 and the unusual cobaltaborane cluster Cp*2Co2(B6H14).
AB  - The new compounds CpV(B(3)H(8))(2), CpCr(B(3)H(8))(2), and Cp(2)Co(2)(B(6)H(14))
      have been synthesized by treating the pentamethylcyclopentadienyl complexes
      [CpVCl(2)](3), [CpCrCl(2)](2), and [CpCoCl](2) with NaB(3)H(8). X-ray
      crystallography shows that CpV(B(3)H(8))(2) and CpCr(B(3)H(8))(2) have the same
      ligand sets but different molecular structures: the vanadium compound contains
      two bidentate B(3)H(8) ligands (i.e., bound to the metal center via two vicinal
      hydrogen atoms), whereas the chromium compound has one bidentate B(3)H(8) ligand
      and one B(3)H(8) ligand bound in an unprecedented fashion via two geminal
      hydrogen atoms. The "gem-bound" B(3)H(8) group itself has an atypical structure
      consisting of a BH(2)-BH(2)-BH(3) triangle with one additional hydrogen atom
      bridging the unique BH(2)-BH(2) edge. The B-B distances are nearly identical
      within experimental error at 1.790(5), 1.792(5), and 1.786(6) Angstrom. The
      relationship between the electronic and molecular structures of the V and Cr
      compounds is briefly discussed. The structure of Cp(2)Co(2)(B(6)H(14)) can be
      viewed in two different ways: as a dicobalt complex in which two CpCo units are
      each bound to four adjacent boron atoms of an S-shaped B(6)H(14) ligand, or as an
      eight-vertex hypho cluster compound. In the former case, the B(6)H(14) ligand is
      best regarded as a dianionic bi-borallyl group H(3)B(mu-H)BH(mu-H)BHBH(mu-H)BH(mu
      H)BH(3) in which one hydrogen at each end of the chain is involved in an agostic
      interaction. From a cluster point of view, the structure of Cp(2)Co(2)(B(6)H(14))
      can be generated by removing three adjacent high-connectivity vertices from the
      eleven-vertex closo polyhedron. The Co-B distances vary from 2.008(5) to 2.183(4)
      Angstrom, and the B-B distances within in the S-shaped chain range from 1.734(8)
      to 1.889(6) Angstrom. Finally, a new synthesis of the known molybdenum compound
      Cp(2)Mo(2)(B(5)H(9)) is described; its structure as established by X-ray
      crystallography closely resembles that of the previously described (C(5)H(4)Me)
      analogue.

PMID- 16910695
TI  - Photocontrolled magnetization of CdS-modified Prussian blue nanoparticles.
AB  - The first photocontrollable magnetic nanoparticles containing CdS and Prussian
      blue (PB) have been created using reverse micelles as nanoreactors. Photoinduced
      electron transfer from CdS to PB in the reverse micelle changed the magnetic
      properties of the composite nanoparticles from ferromagnetic to paramagnetic. The
      magnetization in the ferromagnetic region below 4 K was substantially decreased
      after UV light illumination and could be restored almost to its original level by
      thermal treatment at room temperature. This novel strategy of designing composite
      nanoparticles containing photoconductive semiconductors and magnetic materials to
      create photoswitchable magnetic materials may open many possibilities in the
      development of magneto-optical devices.

PMID- 16910696
TI  - Spectrophotometric method for exploring 3-methyl-2-butene-1-thiol (MBT) formation
      in lager.
AB  - The disappearance of riboflavin absorbance at 445 nm from beers or model beers on
      light exposure is directly linked to light-struck character formation. The
      addition of (+)-catechin, (-)-epicatechin, tryptophol, or ascorbic acid was able
      to reduce, but not stop, absorbance loss or light-struck character formation in
      either model beer or mainstream lager that was exposed to light. When isohumulone
      was present in model beer, the inhibitory effect of (+)-catechin, (-)
      epicatechin, or tryptophol decreased with increasing isohumulone. The
      spectrophotometric method used in this study is a simple and effective method for
      determining light-struck susceptibility.

PMID- 16910697
TI  - Supercritical fluid extraction of bioavailable amino acids from soils and their
      liquid chromatographic determination with fluorometric detection.
AB  - A new procedure with supercritical CO2 modified with 0.5 mL of water and 0.75 mL
      of 0.1 M HCl in situ and 0.75 mL of water on-line at 15 MPa and 50 degrees C for
      45 min was applied for the extraction of bioavailable amino acids from soil
      samples. Total extraction time was 60 min, but more favorable conditions are even
      possible for selected groups of amino acids. All analytes were trapped into 20 mL
      of methanol with satisfactory recovery (94-104%) and determined using high
      performance liquid chromatography with fluorometric detection on a Zorbax Eclipse
      column (4.6 x 75 mm, 3.5 microm) with Na2HPO4 and acetonitrile/methanol/water as
      a mobile phase. Linear calibration curves were obtained (r > 0.999 except 0.99823
      for Ile) with lower limits of detection (S/N = 3) in the range from 1.54 pg (Gly)
      to 13.5 pg (Cy2) or from 18.6 fmol (Ser) to 64.8 fmol (Lys). Validation and
      repeatability data are also given. Comparable results were obtained with a
      robust, commonly used extraction method (0.5 M ammonium acetate, 60 min in
      shaker, followed by filtration and lyophilization). Limiting values of artificial
      release of amino acids were also determined for each soil sample to eliminate any
      false results to ensure that all extracted amino acids originate from soil
      solution and exchangeable bound positions of soil samples.

PMID- 16910698
TI  - Application of quantum dot-antibody conjugates for detection of sulfamethazine
      residue in chicken muscle tissue.
AB  - A new indirect competitive fluorescence-linked immunosorbent assay (cFLISA)
      method for the detection of sulfamethazine (SM2) in chicken muscle tissue was
      demonstrated using quantum dots (QDs) as the fluorescence label coupled with
      secondary antibody. The sensitivity of the cFLISA was compared with that of the
      HPLC method. The 50% inhibition value (IC50) and the limit of detection (LOD) of
      the cFLISA were 7.7 and 1.0 ng/mL, respectively. When SM2 was spiked at levels of
      50, 100, and 200 ng/g, recoveries ranged from 80.6% to 117.4%, with a coefficient
      of variation of 6.9-9.6%. In the incurred sample analysis, the amounts of SM2
      quantified by cFLISA were similar to the results obtained by the HPLC method.
      This study shows that cFLISA could be used as a screening method in practice.

PMID- 16910699
TI  - Determination of multiresidue of avermectins in bovine liver by an indirect
      competitive ELISA.
AB  - An ELISA was developed to detect multiresidues of avermectins (AVMs) including
      abamectin (ABM), ivermectin (IVM), and eprinomectin (EPR) in bovine liver. The
      modified ABM, 4'-O-succinoyl-ABM was conjugated to bovine serum albumin as the
      immunogen for the preparation of polyclonal antibodies to AVMs and conjugated to
      ovalbumin as the coating antigen for the ELISA. Serum with the highest antibody
      titers to AVMs, which had a cross-reactivity of 100% with ABM, 145.4% with EPR,
      and 25% for IVM, was selected for the development of an indirect competitive
      ELISA. The ELISA could detect ABM, IVM, and EPR residues in bovine liver tissues,
      with a limit of quantitation of 1.06 ng/mL for all three AVMs. Optimal pH, ion
      strength, organic solvent, and duration of incubations were investigated to
      increase the sensitivity of the ELISA. Recoveries of these drugs ranged from
      53.8% to 80.6% with inter-assay coefficients of variation (CV) of 3.4-17.9% and
      intra-assay CV of 5.5-14.7%. Analysis results of field samples by the ELISA were
      consistent with those by a previously developed HPLC method. The ELISA can be
      used as a rapid method for screening of AVMs residues in bovine liver.

PMID- 16910700
TI  - Determination of kavalactones in dried kava (Piper methysticum) powder using near
      infrared reflectance spectroscopy and partial least-squares regression.
AB  - Kava (Piper methysticum Forst F.), or awa in the Hawaiian language, has been used
      for thousands of years by the people of the South Pacific Islands, in particular
      Fiji, Vanuatu, Tonga, and Samoa, for social and ceremonial occasions. Kava has
      the unique ability to promote a state of relaxation without the loss of mental
      alertness. Kava recently became part of the herbal pharmacopoeia throughout the
      United States and Europe because of its anxiolytic properties. The active
      compounds are collectively called kavalactones (or kava pyrones). The need for a
      less time-consuming and costly method to determine the concentration of
      kavalactones in dried kava is urgent. The combination of near-infrared
      reflectance spectroscopy (NIRS) and partial least-squares (PLS) methods has been
      found to be a convenient, versatile, and rapid analytical tool for determination
      of kavalactones in dried kava powder. Calibration equations were developed based
      on the analyses of 110 samples with variable physical and chemical properties
      collected over time from Hawaii kava growers and validated by analyses of a set
      of 12 samples with unknown kavalactones concentration. All six major kavalactones
      and the total kavalactones were measured using NIRS with accuracy acceptable for
      commercial use. The NIRS measurements are reproducible and have a repeatability
      on a par with HPLC methods.

PMID- 16910701
TI  - Determination of the 1'S and 1'R diastereomers of metolachlor and S-metolachlor
      in water by chiral liquid chromatography-mass spectrometry/mass spectrometry
      (LC/MS/MS).
AB  - An enantioselective method for the separation and quantification of the
      diastereomer pairs of metolachlor and S-metolachlor in surface and ground waters
      is presented. Samples are purified and concentrated using a C18 (octadecyl
      silica) solid-phase extraction (SPE) procedure and analyzed by chiral column
      liquid chromatography-mass spectrometry/mass spectrometry (LC/MS/MS) interfaced
      with either atmospheric pressure chemical ionization (APcI) or atmospheric
      pressure photoionization (APPI) sources. The overall mean percent procedural
      recoveries (percent relative standard deviations) are 89% (10.6%) for surface
      water and 80% (9.1%) for ground water. The method limit of quantitation (LOQ) is
      0.10 ppb. The method validation was conducted under U.S. EPA FIFRA Good
      Laboratory Practice Guidelines 40 CFR 160.

PMID- 16910702
TI  - Technique for rapid, small-scale analysis of vitamin C levels in fruit and
      application to a tomato mutant collection.
AB  - We present a technique for easy, rapid analysis of both total and reduced forms
      of vitamin C in fruits using microplates and a plate reader. This technique has
      been compared with a spectrofluorometric technique classically used for assaying
      vitamin C in fresh tomato. We have applied these methods to a population of 118
      tomato mutant lines and controls in search of variability for this trait. Six
      lines, identified as having high vitamin C levels, and four lines having low
      vitamin C levels have been chosen for further study. The vitamin C levels have
      been compared with sugar concentration, dry matter content, fruit weight,
      titratable acidity, and firmness. The correlations that often exist in tomato
      varieties between sugar and vitamin C content (positive correlation) or fruit
      weight and vitamin C content (negative correlation) can be uncoupled in the lines
      selected for further analysis.

PMID- 16910704
TI  - Determination of ergosterol in ganoderma spore lipid from the germinating spores
      of Ganoderma lucidum by high-performance liquid chromatography.
AB  - A gradient reversed-phase high-performance liquid chromatography (HPLC) method
      was developed for the separation and determination of free ergosterol in
      ganoderma spore lipid (GSL) extracted from the sporoderm-broken germinating
      spores of Ganoderma lucidum. Sodium hydroxide in methanol was added for the
      hydrolysis of ergosteryl esters to determine the total content of ergosterol in
      GSL by HPLC. A 0.04 M concentration of sodium hydroxide in reaction mixtures was
      appropriate for the complete hydrolysis of ergosteryl esters without a
      significant loss of ergosterol during saponification. In addition, the ergosterol
      content in four commercial GSL softgel supplements from four different firms was
      determined. The results showed that the ergosterol content in these samples had
      significant differences. Ergosterol content may be a suitable marker for
      evaluating the quality of GSL products.

PMID- 16910703
TI  - Application of Fourier transform midinfrared spectroscopy to the discrimination
      between Irish artisanal honey and such honey adulterated with various sugar
      syrups.
AB  - A collection of authentic artisanal Irish honeys (n = 580) and certain of these
      honeys adulterated by fully inverted beet syrup (n = 280), high-fructose corn
      syrup (n = 160), partial invert cane syrup (n = 120), dextrose syrup (n = 160),
      and beet sucrose (n = 120) was assembled. All samples were adjusted to 70 degrees
      Bx and scanned in the midinfrared region (800-4000 cm(-1)) by attenuated total
      reflectance sample accessory. By use of soft independent modeling of class
      analogy (SIMCA) and partial least-squares (PLS) classification, authentic honey
      and honey adulterated by beet sucrose, dextrose syrups, and partial invert corn
      syrup could be identified with correct classification rates of 96.2%, 97.5%,
      95.8%, and 91.7%, respectively. This combination of spectroscopic technique and
      chemometric methods was not able to unambiguously detect adulteration by high
      fructose corn syrup or fully inverted beet syrup.

PMID- 16910705
TI  - Antioxidant properties of wheat as affected by pearling.
AB  - The effects of pearling on the content of phenolics and antioxidant capacity of
      two Canadian wheat classes, namely, Canada Western Amber Durum; Triticum turgidum
      L. var. durum; CWAD) and Canada Western Red Spring; Triticum aestivum L.; CWRS)
      were examined. The antioxidant activity of wheat phenolics was evaluated using
      oxygen radical absorbance capacity (ORAC), inhibition of photochemiluminescence
      (PCL), Rancimat method, inhibition of oxidation of low-density lipoprotein, and
      DNA. The phenolic composition of wheat extracts was determined using high
      performance liquid chromatography. The antioxidant capacity of both pearled
      grains and byproducts significantly decreased as the degree of pearling
      increased. Among grains, the unprocessed whole grains demonstrated the highest
      antioxidant capacity. The byproducts always demonstrated higher antioxidant
      capacity compared to the pearled grains, regardless of the wheat class. The
      resultant byproducts from 10-20% pearling possessed the highest antioxidant
      capacity. Processing of cereals may thus exert a significant effect on their
      antioxidant activity. The concentration of grain antioxidants is drastically
      reduced during the refining process. As phenolic compounds are concentrated in
      the outermost layers, the bran fractions resulting from pearling may be used as a
      natural source of antioxidants and as value-added products in the preparation of
      functional food ingredients or for enrichment of certain products.

PMID- 16910706
TI  - Quercetin content in field-cured onions (Allium cepa L.): effects of cultivar,
      lifting time, and nitrogen fertilizer level.
AB  - Variation in quercetin content was investigated in field-cured onions (Allium
      cepa L.) that had been supplied with different nitrogen fertilizer levels and
      lifted at different developmental stages. Quercetin content varied significantly
      between years and was well correlated to global radiation in August. Field curing
      generally resulted in significant increases in quercetin content compared to
      levels at lifting. Nitrogen fertilizer level did not affect quercetin content,
      suggesting that nitrogen leakage from soil may be minimized without effects on
      flavonol content. Lifting time had minor effects on quercetin content in field
      cured onions. Cultivar differences in quercetin content were significant but not
      consistent in all years. Quercetin content increased significantly less in dark
      environments compared to field curing, but some quercetin synthesis occurred
      regardless of light. Field curing with or without foliage still attached did not
      affect quercetin content, suggesting that no transportation from the foliage to
      the scales occurred.

PMID- 16910707
TI  - Proteomic analysis of Caco-2 cells treated with monacolin K.
AB  - Monascus species is an important traditional fermentation fungus used on food.
      Monacolin K (a secondary metabolite of Monascus, a competitive inhibitor of 3
      hydroxy-3-methylglutaryl coenzyme A reductase) in inhibition of mevalonate
      synthesis may result in reductions of isoprenoid prenylation in cells. Impairment
      of protein isoprenoid prenylation has been related to anticancer effect in cancer
      cells. As a functional food for Monascus, however, the molecular mechanisms
      responsible for the anti-proliferate effect of monacolin K in cancer cells are
      not clear. We used proteomic analysis by two-dimensional gel electrophoresis,
      matrix-assisted laser desorption ionization time-of-flight/time-of-flight mass
      spectrometry (MALDI-TOF/TOF MS), tandem mass spectrometry (MS/MS), and database
      interrogation to separate and identify the proteins of Caco-2 cells treated with
      monacolin K. The results showed that monacolin K inhibited the proliferation of
      Caco-2 cells in a dose-dependent manner. The identified proteins in proteomic
      analysis included anti-oxidation enzymes related to reactive oxygen species
      stress, cytoskeleton proteins, glycolytic enzymes, and enzymes involved in
      mediating protein interactions. Furthermore, glutathione S-transferase P 1 and
      cytoskeleton-8, -18, and -19 revealed a down-regulation in a dose-dependent
      manner in exposure of Caco-2 cells to monacolin K.

PMID- 16910708
TI  - Stability and antioxidant activity of black currant anthocyanins in solution and
      encapsulated in glucan gel.
AB  - The effects of ferric and ferrous ions, pH, and temperature on the stability and
      antioxidant activity of black currant anthocyanins (BCA) were studied, and the
      recovery of BCA from glucan gel [mixed linked (1-->3,1-->4)-beta-D-glucan] after
      using different encapsulating procedures was determined. The degradation of
      individual anthocyanins follows first-order kinetics and shows Arrhenius
      temperature dependence. The activation energies of individual anthocyanins,
      evaluated over the temperature range 60-100 degrees C, decrease with an increase
      in pH. While the antioxidant activity of BCA, measured by the ferric reducing
      antioxidant power assay, decreased with the degradation of anthocyanins, the
      completely degraded products still exhibited approximately 30% of the initial
      antioxidant activity. Ferric ions have a detrimental effect on the stability of
      BCA, especially for delphinidins. Freeze drying of encapsulated BCA gives
      approximately 20% higher recovery of individual anthocyanins than infrared
      drying.

PMID- 16910709
TI  - Use of beer bran as an adsorbent for the removal of organic compounds from
      wastewater.
AB  - Beer bran was found to effectively adsorb several organic compounds, such as
      dichloromethane, chloroform, trichloroethylene, benzene, pretilachlor, and
      esprocarb. Equilibrium adsorption isotherms conformed to the Freundlich isotherm
      (log-log linear). Adsorption of these organic compounds by beer bran was observed
      in the pH range of 1-11. At equilibrium, the adsorption efficiency of beer bran
      for benzene, chloroform, and dichiloromethane was higher than that of activated
      carbon. The removal of these organic compounds by beer bran was attributed to the
      uptake by intracellular particles called spherosomes. The object of this work was
      to investigate several adsorbents for the effective removal of organic compounds
      from wastewater.

PMID- 16910710
TI  - Predominant expression of diploid mandarin leaf proteome in two citrus mandarin
      derived somatic allotetraploid hybrids.
AB  - Fusion of citrus diploid parental protoplasts generates allotetraploid hybrids
      which do not retain their parental traits with regard to leaf aroma compound
      biosynthesis. The aim of this study was thus to examine hybrid leaf proteomes in
      comparison with their parents. Leaf soluble proteins from two citrus
      allotetraploid hybrids (mandarin + lime and mandarin + kumquat) and their diploid
      parents (mandarin, lime, and kumquat) were submitted to 2-D gel electrophoresis.
      Leaf proteome maps of the tetraploid hybrids were compared with those of their
      parents on the basis of the presence/absence of spots and of their spot relative
      volumes. The two allotetraploid hybrid maps were found closer to that of their
      mandarin parent than to those of their nonmandarin parents in terms of the
      presence/absence of spots as well as at a quantitative level. This approach has
      to be related to the already observed dominance of mandarin in allotetraploids
      with regard to volatile compound biosynthesis in leaves.

PMID- 16910711
TI  - Effect of molecular sieves on lipase-catalyzed esterification of rutin with
      stearic acid.
AB  - Rutin was acylated with stearic acid in the esterification reaction catalyzed by
      immobilized Candida antarctica lipase B (Novozym 435) in tert-amyl alcohol with
      and without molecular sieves. The lipophilic rutin stearate was synthesized by
      this method, which had a potential use in food, cosmetics, and pharmacy. The
      structure of rutin stearate was characterized by spectral methods of 1H NMR and
      13C NMR, Fourier transform infrared, and UV-vis. The results suggested that the
      regioselectivity of the lipase-catalyzed esterification of rutin was specific at
      the C(4''')-position of the rhamnose moiety. It was found that the addition of
      molecular sieves increased both the reaction rate and the yield. The time effect
      of adding molecular sieves in the reaction system on the conversion of rutin
      stearate was further examined. Instead of adding molecular sieves at the
      beginning of the reaction, the addition of molecular sieves at 5, 18, 24, 31, and
      44 h after the beginning of the reaction was also applied. The final conversion
      for the case to add molecular sieves at 24 h after the beginning of reaction was
      the highest, with the conversion yield about 46%.

PMID- 16910712
TI  - Assessment of urea degradation rate in model wine solutions by acid urease from
      Lactobacillus fermentum.
AB  - The specific activity (piA) of a whole cell acid urease preparation was assessed
      in model wine solutions at different levels of malic (M) and lactic acids,
      metabisulfite, ethanol, and pH by performing a central composite design. M and
      then pH were found to be the most controlling variables, their effects being
      practically coincident but of opposite sign. For urea concentrations up to
      approximately 1 mol m(-3) the ammonium formation rate was assumed of the pseudo
      first-order with respect to urea, this being confirmed by two independent
      validation tests performed at 20 degrees C for as long as 24 h. In the case of
      real wines the effective pseudo-first-order kinetic rate constants were found to
      be smaller than those pertaining to the model solutions having the same wine
      composition and pH by a factor varying from 10 to 1000, this affecting
      significantly the specific urease treatment costs per liter of wine treated.

PMID- 16910713
TI  - Biocatalytic production of dihydrocoumarin from coumarin by Saccharomyces
      cerevisiae.
AB  - Natural dihydrocoumarin, which is of great interest in the flavor industry, was
      biotechnologically produced from pure coumarin or tonka bean meal with
      Pseudomonas orientalis, Bacillus cereus, and various Saccharomyces cerevisiae
      strains. Coumarin was shown to be converted to melilotic acid, which yielded
      dihydrocoumarin upon distillation during purification. About 1.0 g/L product was
      obtained from 25 g/L tonka beans with S. cerevisiae within 147 h. This
      dihydrocoumarin thus fulfills all of the criteria of a natural raw material and
      can be used as a natural flavoring in accordance with U.S. and European Union
      regulations.

PMID- 16910714
TI  - Addition of pectin and soy soluble polysaccharide affects the particle size
      distribution of casein suspensions prepared from acidified skim milk.
AB  - Pectins are negatively charged polysaccharides employed as stabilizers in
      acidified milk dispersions, where caseins aggregate because of the low pH and
      serum separation needs to be prevented. The objective of this research was to
      study the effect of charge on the stabilizing functionality of the polysaccharide
      in acid milk drinks. Unstandardized pectins with various charges (as degree of
      esterification, DE) as well as soybean soluble polysaccharide (SSPS) were tested
      for their stabilizing behavior as a function of pH and concentration. Skim milk
      was acidified by glucono-delta-lactone and then homogenized in the presence of
      polysaccharide at different pH values (in the range from 4.2 to 3.0).
      Measurements of particle size distribution demonstrated that pectins with a DE of
      71.4, 68.6, and 67.4 stabilized milk at pH > 4.0. Pectins with a lower DE (63.9%)
      needed a higher concentration (0.4%) at the same pH to show a monomodal
      distribution of particle sizes. Pectins with lower DE (<50%) did not stabilize
      the dispersions. Although this difference in behavior was attributed mainly to
      the pectin charge, the efficiency in stabilizing the casein dispersion decreased
      with decreasing pectin size. For example, the high methoxyl pectin (HMP) with
      63.9 DE was smaller in size than the HMPs with a higher charge. Pectins showed a
      pH-dependent stabilization effect, as at pH < 4.0 the dispersions contained
      aggregates. When SSPS was used to stabilize acid milk, at pH < 4.0, it showed a
      better stabilization behavior than HMP. When SSPS and pectin were used in
      combination, the particle size distribution of the acid milk dispersion was pH
      dependent, and results were similar to those for samples containing pectin alone.
      This suggested that in the mixture, pectin dominated the behavior over SSPS, even
      when an excess of SSPS was added to the dispersions before homogenization.

PMID- 16910715
TI  - Carotenoid profile modification during refrigerated storage in untreated and
      pasteurized orange juice and orange juice treated with high-intensity pulsed
      electric fields.
AB  - A comparative study was made of the evolution and modification of various
      carotenoids and vitamin A in untreated orange juice, pasteurized orange juice (90
      degrees C, 20 s), and orange juice processed with high-intensity pulsed electric
      fields (HIPEF) (30 kV/cm, 100 micros), during 7 weeks of storage at 2 and 10
      degrees C. The concentration of total carotenoids in the untreated juice
      decreased by 12.6% when the juice was pasteurized, whereas the decrease was only
      6.7% when the juice was treated with HIPEF. Vitamin A was greatest in the
      untreated orange juice, followed by orange juice treated with HIPEF (decrease of
      7.52%) and, last, pasteurized orange juice (decrease of 15.62%). The decrease in
      the concentrations of total carotenoids and vitamin A during storage in
      refrigeration was greater in the untreated orange juice and the pasteurized juice
      than in the juice treated with HIPEF. During storage at 10 degrees C, auroxanthin
      formed in the untreated juice and in the juice treated with HIPEF. This
      carotenoid is a degradation product of violaxanthin. The concentration of
      antheraxanthin decreased during storage, and it was converted into mutatoxanthin,
      except in the untreated and pasteurized orange juices stored at 2 degrees C.

PMID- 16910716
TI  - Fatty acid profiles of processed chicken egg yolks.
AB  - The fatty acid compositions of egg yolks subjected to industrial processing
      treatments, namely, homogenization, pasteurization, drying, and "omega-3
      enrichment", were studied. In general, the total contents of C16:0, C18:0, C18:1
      n-9, and C18:2 n-6 fatty acids accounted for close to 90% of the total fatty
      acids. Statistical analysis of the data revealed correlations among the fatty
      acids; significant differences existed depending on the egg source and type of
      processing. Yolk samples enriched with omega-3 fatty acids clustered together
      owing to their higher C16:0, C16:1 n-7, C18:3 n-6, and C24:0 contents.
      Nonpasteurized/non-heat-treated samples formed another cluster because of their
      higher C18:1 n-11 and C18:1 n-9 contents, and the remaining samples formed
      another group due to their higher proportions of C18:0, C18:2 n-6, and C20:4 n-6.
      The relative proportions of essential fatty acids were similar in the four types
      of samples examined.

PMID- 16910717
TI  - Quantitation of the main constituents of some authentic grape-seed oils of
      different origin.
AB  - This paper describes the composition of 30 grape-seed oils obtained from France,
      Italy, and Spain during 2002-2003. Oils were extracted from the seeds using small
      scale industrial solvent extraction equipment and analyzed in their unrefined
      state using standard methods for fatty acids, fatty acids in the triacylglycerol
      2-position, tocopherols and tocotrienols, triglycerides, sterols, steradienes,
      and iodine value. Values for the composition of the sterols, triglycerides, fatty
      acids, iodine value, and tocopherol composition were generally in good agreement
      with the results of previous similar surveys. Steradienes (stigmastadiene,
      campestadiene, stigmastatriene, and campestatriene) were detected in the oil and
      were probably formed from sterols during the extraction process.

PMID- 16910718
TI  - Quantitation of the main constituents of some authentic sesame seed oils of
      different origin.
AB  - This paper describes the composition of sesame seed oils obtained from seeds
      collected from five countries that are major suppliers of traded sesame seed oil.
      Oils were extracted from the seeds using small-scale industry pressing equipment
      and analyzed using standard methods for fatty acids, fatty acids in the
      triglyceride 2-position, tocopherols and tocotrienols, triglycerides, sterols,
      steradienes, and iodine value. Values for the composition of the sterols,
      triglycerides, fatty acids, iodine value, and tocopherol composition were
      generally in good agreement with the results published elsewhere. All of the oils
      from roasted seeds contained low levels of the sterol degradation products
      stigmasta-3,5-diene and campesta-3,5-diene, which were probably formed by
      dehydration of the parent sterols during roasting.

PMID- 16910719
TI  - Antioxidant capacity of black currant varies with organ, season, and cultivar.
AB  - Small berries such as black currant constitute one of the important sources of
      potential health-promoting phytochemicals because these fruits are rich sources
      of compounds with high antioxidant properties. In this work, antioxidant
      capacities of different parts (buds, leaves, fruits) of various black currant
      cultivars were compared throughout the growing season with the aim to prepare
      extracts with high antioxidant capacity. Buds (opened, at the end of March) and
      leaves (in June) had a higher content in phenolics and antioxidants than fully
      ripened berries (in July) and the best yield (per branch) was obtained with the
      leaves collected in June due to their higher biomass. The differences observed
      among the eight cultivars tested were small. Concerning flavonols, quercetin was
      dominant in all organs and cultivars, myricetin varied widely among the
      cultivars, and kampferol was very low.

PMID- 16910720
TI  - Phyto-saponins as a natural adjuvant for delivery of agromaterials through plant
      cuticle membranes.
AB  - With growing use of synthetic adjuvants in modern agriculture, their impacts on
      the environment are being questioned. In a search for an environmentally safe
      phyto-adjuvant, we have investigated natural glycosidic saponin for delivery of
      agromaterials through plant cuticle membranes. Four saponin preparations from
      Quillaja saponaria bark (QE), obtained from Sigma-Aldrich, and Balanites
      aegyptiaca fruit mesocarp (ME), kernel (KE), and root (RE), isolated and
      characterized in our laboratory, were used for testing the delivery of [14C]-2,4
      dichlorophenoxyacetic acid (2,4-D) across isolated intact astomatous adaxial
      Citrus grandis leaf cuticle membranes (CMs). The results showed that both Q.
      saponaria and B. aegyptiaca saponin preparations enhanced delivery of 2,4-D
      through CMs. Among the saponin preparations, ME exhibited a significantly higher
      level of delivery of 2,4-D with a concentration effect (2% being the highest).
      Transmission electron microscope (TEM) and dynamic light scattering (DLS)
      characterization of these saponin preparations in aqueous solution clearly
      demonstrated the formation of nanoscale vesicles. Various possibilities for a
      natural amphiphatic phyto-saponin as a delivery adjuvant through CMs are
      discussed.

PMID- 16910721
TI  - Uptake and transformation of pesticide metabolites by duckweed (Lemna gibba).
AB  - Uptake and transformation of 14C-labeled metabolites from several pesticides, 3
      methyl-4-nitrophenol (1), 3,5-dichloroaniline (2), 3-phenoxybenzoic acid (3),
      (R,S)-2-(4-chlorophenyl)-3-methylbutanoic acid (4), and (1RS)-trans-3-(2,2
      dichlorovinyl)-2,2-dimethylcyclopropanecarboxylic acid (5), were examined by
      using duckweed (Lemna gibba) in Hoagland's medium. More uptake into duckweed from
      the exposure water at pH 7.0 was observed for non-ionized 1 and 2 than for 3-5 in
      an ionized form, and their hydrophobicity accounted for these differences. While
      carboxylic acids 4 and 5 were scarcely transformed in duckweed, 1-3 mainly
      underwent phase II conjugation with glucose for 1 and 2, malic acid for 3,
      glutamic acid for 2, and malonylglucose for 3, the chemical identities of which
      were confirmed by various spectrometric analyses (LC-MS, LC-MS/MS, and NMR)
      and/or HPLC cochromatography with reference synthetic standards.

PMID- 16910722
TI  - Studies on water transport through the sweet cherry fruit surface. 11. FeCl3
      decreases water permeability of polar pathways.
AB  - The effect of FeCl3 (10 mM) on osmotic water uptake into detached sweet cherry
      fruit (Prunus avium L.) and on the (3)H2O permeability (P(d)) of excised exocarp
      segments (ES) or enzymatically isolated cuticular membranes (CM) was
      investigated. ES or CM were mounted in an infinite dose diffusion system, where
      diffusion is monitored from a dilute donor solution through an interfacing ES or
      CM into a receiver solution under quasi steady-state conditions. In the absence
      of FeCl3, (3)H2O diffusion through stomatous ES was linear over time, indicating
      that P(d) was constant. Adding FeCl3 to the donor decreased P(d) by about 60%.
      P(d) remained at a decreased level when replacing the FeCl3 donor again by
      deionized water. The decrease in P(d) was positively and linearly related to the
      stomatal density of the ES. There was no effect of FeCl3 on the P(d) of
      astomatous sweet cherry fruit ES or CM regardless of the presence of wax
      (epicuticular or cuticular). FeCl3 decreased P(d) when added to the donor (-63%)
      or receiver (-16%), but there was no effect when it was added to donor and
      receiver solutions simultaneously. The decrease in P(d) depended on the pH of the
      receiver and the presence of citrate buffer. There was no effect of FeCl3 with
      citrate buffer as a receiver regardless of pH (range 2.0-6.0). When using
      nonbuffered receiver solutions with pH adjusted to pH 2.0, 3.0, 4.5, or 6.0,
      FeCl3 markedly decreased (3)H2O diffusion at pH > or = 3 but had no effect at pH
      2.0. FeCl3 increased the energy of activation (E(a)) for (3)H2O diffusion (range
      15-45 degrees C) through stomatous ES but had no significant effect in astomatous
      CM. The increase in E(a) by FeCl3 was positively related to stomatal density.
      FeCl3 decreased the P(d) for 2-(1-naphthyl)[1-(14)C]acetic acid (NAA) and 2,4
      dichloro[U-(14)C]phenoxyacetic acid (2,4-D) in stomatous ES. The magnitude of the
      effect depended on the degree of dissociation and was larger for the dissociated
      acids (pH 6.2) than for the nondissociated acids (pH 2.2). Incubating whole fruit
      in isotonic solutions of selected osmotica resulted in significant water uptake
      that was inversely related to the molecular weight of the osmotica and was
      consistently lower for fruit treated with FeCl3. The FeCl3 induced decrease in
      water fluxes was larger for osmotica having a low molecular weight than for those
      with a higher molecular weight. Our data indicate that FeCl3 decreased the
      permeability of the stomatous sweet cherry exocarp to water and other polar
      substances by pH-dependent formation of precipitates that decrease transport
      along polar pathways. Decreasing the permeability of polar pathways by a
      precipitation reaction is a useful target in developing strategies against rain
      induced fruit cracking.

PMID- 16910723
TI  - Chemical composition and antioxidant properties of clove leaf essential oil.
AB  - The antioxidant activity of a commercial rectified clove leaf essential oil
      (Eugenia caryophyllus) and its main constituent eugenol was tested. This
      essential oil comprises in total 23 identified constituents, among them eugenol
      (76.8%), followed by beta-caryophyllene (17.4%), alpha-humulene (2.1%), and
      eugenyl acetate (1.2%) as the main components. The essential oil from clove
      demonstrated scavenging activity against the 2,2-diphenyl-1-picryl hydracyl
      (DPPH) radical at concentrations lower than the concentrations of eugenol,
      butylated hydroxytoluene (BHT), and butylated hydroxyanisole (BHA). This
      essential oil also showed a significant inhibitory effect against hydroxyl
      radicals and acted as an iron chelator. With respect to the lipid peroxidation,
      the inhibitory activity of clove oil determined using a linoleic acid emulsion
      system indicated a higher antioxidant activity than the standard BHT.

PMID- 16910724
TI  - Composition, enantiomeric distribution, and antibacterial activity of the
      essential oil of Achillea ligustica All. from Corsica.
AB  - The essential oil of Achillea ligustica from Corsica was investigated by gas
      chromatography (GC) and gas chromatography-mass spectrometry (GC-MS). A total of
      82 compounds representing 94.0% of the oil were tentatively identified. The main
      constituents were the camphane derivatives, representing >30% (camphor, 21.3%;
      borneol, 6.2%; bornyl acetate, 3.5%) of the whole oil, and santolina alcohol
      (19.3%). The enantiomeric distribution of 8 chiral constituents was determined by
      GC-MS using two enantioselective stationary phases (DIME-beta-CD and Lipodex-E).
      Racemic santolina alcohol, required for optimization of the enantioselective GC
      conditions, was prepared by an original two-step synthesis from 2,5-dimethylhexa
      2,4-diene. The whole essential oil was tested for its antibacterial activity
      against a wide range of bacteria using a paper disk method. The results show a
      promising activity against Streptomyces species.

PMID- 16910725
TI  - Composition of the essential oils of Thymus and Origanum species from Algeria and
      their antioxidant and antimicrobial activities.
AB  - The composition of the essential oils of Origanum and Thymus species restricted
      to Algeria and the North Africa region was determined. Antioxidant and
      antibacterial activities of the isolated essential oils were also determined. The
      oils of oregano plants were strongly characterized by p-cymene (16.8-24.9%),
      gamma-terpinene (16.8-24.9%), thymol (8.4-36.0%), and carvacrol (1.1-29.7%), a
      thymol chemotype for Origanum floribundum and a alpha-terpineol chemotype for
      Thymus numidicus being described for the first time. The strains of Listeria
      monocytogenes tested were relatively resistant to the action of essential oils of
      either Origanum or Thymus species. All essential oils possessed antioxidant
      activity, but this was dependent on the specific chemical composition and the
      method employed to determine such activity.

PMID- 16910726
TI  - Hydrolysis and transformation of grape glycosidically bound volatile compounds
      during fermentation with three Saccharomyces yeast strains.
AB  - The ability of three Saccharomyces wine yeasts (S. cerevisiae AWRI 838, S.
      cerevisiae AWRI 1537, and S. bayanus AWRI 1375) to liberate volatile compounds
      from sugar-bound aroma precursors was investigated using synthetic and grape
      glycosides under different experimental conditions. In model systems involving
      the incubation of yeast cells with either synthetic or grape-derived glycosides
      under conditions more favorable for glycosidase activities and less favorable for
      acid-catalyzed hydrolysis (pH 5.0 and 30 degrees C), all yeast strains studied
      proved to be capable of hydrolyzing glycosides, with S. bayanus AWRI 1375
      displaying greater hydrolytic activity than S. cerevisiae AWRI 838 and AWRI 1537.
      During the fermentation of a chemically defined grape juice-like medium
      containing glycosidic precursors extracted from Vitis vinifera cv. White
      Frontignac (synonym Muscat a Petit Grains Blanc), all yeasts promoted a
      significant hydrolysis of different precursors, which varied according to the
      chemical structures of both the sugar and the aglycon moieties, as determined by
      GC-MS analysis of trifluoroacetylated derivatives. Hydrolysis of the White
      Frontignac derived glycosidic precursors during fermentation resulted in the
      release of monoterepene alcohols, terpene oxides, terpene diols, and 3-oxo-alpha
      ionol, demonstrating the significant potential of these yeast strains to
      contribute to wine varietal volatile composition during alcoholic fermentation.

PMID- 16910727
TI  - Characterization of aroma-active compounds in raw and cooked pine-mushrooms
      (Tricholoma matsutake Sing.).
AB  - The characteristic aroma-active compounds in raw and cooked pine-mushrooms
      (Tricholoma matsutake Sing.) were investigated by gas chromatography-olfactometry
      using aroma extract dilution analysis. 1-Octen-3-one (mushroom-like) was the
      major aroma-active compound in raw pine-mushrooms; this compound had the highest
      flavor dilution factor, followed by ethyl 2-methylbutyrate (floral and sweet),
      linalool (citrus-like), methional (boiled potato-like), 3-octanol (mushroom-like
      and buttery), 1-octen-3-ol (mushroom-like), (E)-2-octen-1-ol (mushroom-like), and
      3-octanone (mushroom-like and buttery). By contrast, methional, 2-acetylthiazole
      (roasted), an unknown compound (chocolate-like), 3-hydroxy-2-butanone (buttery),
      and phenylacetaldehyde (floral and sweet), which could be formed by diverse
      thermal reactions during the cooking process, together with C8 compounds, were
      identified as the major aroma-active compounds in cooked pine-mushrooms.

PMID- 16910728
TI  - Efficient digestion and structural characteristics of cell walls of coffee beans.
AB  - Screening of effective food-processing cellulase for digestion of cell walls of
      coffee beans was carried out, and the cellulase from Trichoderma sp. was
      selected. The digestion of the cell walls of green and roasted coffee beans was
      carried out by sequential procedures of alkali boiling (0.1 M Na2CO3 buffer, pH
      10, and 0.1 M NaOH), cellulase digestion, autoclaving with 0.1 M NaOH, and
      cellulase redigestion. The total digestion yields were >95 and >96%,
      respectively. The cell walls became thin, and the final residues of the cell
      walls were easily broken into small pieces. The neutral sugar analysis of the
      digestion or the extract and the residues and the microscopy observations with
      staining with toluidine blue O, Yariv reagent, and calcofluor for the residue in
      each step were investigated. Four structures, the galactomannan-cellulose (center
      part), the membrane of the arabinogalactan protein, the cellulose-rich
      galactomannan layer, and the arabinogalactan protein-rich layers (outer part),
      were found in the cell walls.

PMID- 16910729
TI  - Iron chelation by the powerful antioxidant flavonoid quercetin.
AB  - Chelation of the bare and hydrated iron(II) cation by quercetin has been
      investigated at the DF/B3LYP level in the gas phase. Several complexed species
      arising from neutral and anionic forms of the ligand have been taken into
      account. Both 1:1 and 1:2 metal/flavonoid stoichiometries have been considered.
      Results indicate that among the potential sites of chelation present on
      quercetin, the oxygen atoms belonging to the 3-hydroxy and 4-oxo, and to the 5
      hydroxy and 4-oxo groups, are the preferred ones. Time-dependent density
      functional theory (TDDFT) calculations, used to reproduce the electronic UV-vis
      spectra of isolated quercetin and its complexes with Fe2+, were also performed in
      methanol and dimethylsulfoxide.

PMID- 16910730
TI  - Electromigration of chitosan D-glucosamine and oligomers in dilute aqueous
      solutions.
AB  - The electromigration behavior of chitosan D-glucosamine and oligomers with a
      degree of polymerization from 1 to 6 in dilute aqueous systems containing either
      NaCl or KCl salt at 0.01, 0.05, and 0.1 M at pH values from 2 to 9 was evaluated.
      The results showed that the electromigration of the chitosan D-glucosamine and
      oligomers did not change by changing the type of salt in the running medium and
      that the pH had a significant effect on the direction of migration under an
      external electric field. In addition, the increase in the ionic strength of the
      medium caused a significant decrease on the absolute value of the electrophoretic
      mobility, and the highest values of the electromobility were observed in water.
      However, the ionic strength had no significant effect on the electrophoretic
      mobilities at pH 2 in comparison with the other pH values. The dimer showed the
      highest electrophoretic mobility in the alkaline zone of the pH. At pH values
      lower than the pKa of the D-glucosamine, the chitosan D-glucosamine, and
      oligomers migrated toward the anode, where the amine groups are protonated and
      carry positive charge. At higher pH values, chitosan D-glucosamine and oligomers
      migrated toward the anode, even though they did not carry any electric charge.
      The contribution of the difference in the dielectric constants between the
      solvent and the solute to this phenomenon was highlighted. It was shown that the
      glucose moiety contributes to the direction of migration of the chitosan D
      glucosamine and oligomers under alkaline conditions and that the difference in
      the dielectric constant of glucose and the solvent accounts for the direction and
      the extent of electromobility.

PMID- 16910731
TI  - Optimization in the preparation of coenzyme Q10 nanoliposomes.
AB  - The optimal formulation of coenzyme Q10 (CoQ10) nanoliposomes and the feasibility
      of production in a pilot scale were investigated. The nanoliposomes were prepared
      by ethanol injection and sonication techniques for a desired vesicle size in the
      laboratory. Optimization of formulation in the preparation of CoQ10 nanoliposomes
      was achieved by an orthogonal array design. The best formulation was found to be
      phospholipid/CoQ10/cholesterol/Tween 80 (2.5:1.2:0.4:1.8, w/w) with phosphate
      buffer solution (pH 7.4, 0.01 M) as the hydration media. The z-average diameter
      (D(z)) was about 68 nm. The encapsulation efficiency was greater than 95% with a
      retention ratio higher than 90% and a particle size change lower than 10% after
      storage at 4 degrees C in the dark for 90 days. CoQ10 incorporation resulted in a
      dramatic increase of the microviscosity of nanoliposomes and inhibited the
      peroxidation of phospholipid. The D(z) of CoQ10 nanoliposomes produced in a pilot
      scale was about 67 nm. Results suggest that the technology developed by this
      investigation is practical to produce the CoQ10 nanoliposomes with the expected
      encapsulation quality and stability not only in the laboratory but also in a
      pilot scale.

PMID- 16910732
TI  - Characterization of reaction products formed in a model reaction between pentanal
      and lysine-containing oligopeptides.
AB  - Aldehydes formed as a result of lipid oxidation form fluorophores after binding
      to proteins. The structure of the fluorophores formed by reaction between
      saturated aldehydes and lysine has not yet been identified. The reaction products
      formed in the reaction between pentanal and oligopeptides were studied by
      fluorescence spectroscopy and mass spectrometry. The emission spectra showed an
      increase in fluorescence intensity with incubation time, and the rates were
      linear with the concentration of pentanal. Matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry analyses of the reaction
      products suggested a molar relation for peptide:pentanal of 1:4. Further tandem
      mass spectrometry analysis of one of the modified peptides (Pro-Thr-His-Ile-Lys
      Trp-Gly-Asp) strongly suggested binding of one pentanal molecule to the amino
      terminal proline and three pentanal molecules bound to the lysine residue. The
      latter species is suggested to be the actual fluorophore, through the formation
      of conjugated double bonds, and a possible reaction pathway through a combination
      of aldol condensation of pentanal and Schiff base formation with the lysine is
      suggested.

PMID- 16910733
TI  - Gamma-irradiation influence on the structure and properties of calcium caseinate
      whey protein isolate based films. Part 1. Radiation effect on the structure of
      proteins gels and films.
AB  - Brookfield viscosimetry, Fourier transform infrared spectroscopy, transmission
      electron microscopy (TEM), and measurements of the texture strength of gels
      formed with CaCl2 and the mechanical and barrier properties of the film were
      applied in studies of gel formation and structural and mechanical properties of
      gels and films prepared using calcium caseinate (CC)-whey protein isolate (WPI)
      glycerol (1:1:1), control, and irradiated with 60Co gamma rays using a 32 kGy
      dose. The irradiated gels have appeared to be more "fine-stranded" as compared to
      the more "particulate" control gels and lead to the formation of more rigid films
      with improved mechanical strength and barrier properties. This results from cross
      linking and the modification of protein conformations were induced by
      irradiation, in particular the increase in the beta-sheet and beta-strand
      contents. Structural modifications taking place in CC-WPI composition are related
      to modifications taking place separately in CC and WPI. Improvement of the
      properties of the films after irradiation corresponds to the increased density of
      the cross-linked material because no change in the porosity of the films was
      observed by TEM.

PMID- 16910734
TI  - Detection of adulteration of poppy seed oil with sunflower oil based on volatiles
      and triacylglycerol composition.
AB  - Although poppy seed oil is an expensive article of trade, no literature about
      identification methods for adulteration with cheaper vegetable oils, like
      sunflower oil, has been published. This kind of adulteration is a challenge for
      routine analytical methods, such as the determination of fatty acid composition,
      because of almost similar fatty acid ratios. The detection of adulteration of
      poppy seed oils with sunflower oils at different levels (5-40%, w/w) by using
      SPME-GC-MS and MALDI-ToF-MS is the subject of our investigation. With the
      mentioned SPME-GC-MS method, it was possible to detect an admixture of sunflower
      oils in all relevant (5-40%) amounts by using alpha-pinene as a marker compound.
      Admixture of sunflower oil with high levels of triolein (high-oleic acid type)
      could be undoubtedly detected by MALDI-MS down to the 5-10% level. In contrast,
      adulteration of pure poppy seed oil by "standard" sunflower oils remained
      indistinguishable using this MALDI-MS.

PMID- 16910735
TI  - Physical stability of liposomes prepared from milk fat globule membrane and soya
      phospholipids.
AB  - Previous research has shown that liposomes prepared from a milk fat globule
      membrane (MFGM) phospholipid fraction had a significantly higher phase transition
      temperature, thicker membrane, and lower membrane permeability than liposomes
      prepared from soya phospholipid material. Subsequent investigations into the
      relative stability of the two liposome dispersions have found that the MFGM
      phospholipid liposomes are more stable than their soya counterparts in a range of
      pH conditions, at a variety of storage and processing temperatures, and in the
      presence of mono- and divalent cations. These results illustrate some potential
      advantages in the use of MFGM phospholipids for the manufacture of liposomes for
      use in food systems.

PMID- 16910736
TI  - New constituents from noni (Morinda citrifolia) fruit juice.
AB  - Morinda citrifolia L. (Rubiaceae), known as noni, has a long history of
      traditional use in the Hawaiian and Tahitian islands. More recently, an array of
      commercial noni fruit juice products are gaining popularity as dietary
      supplements, with claims of anticancer and immunostimulant activities. The
      biologically active principles of noni are not fully known. In continuation of
      work on the isolation of markers from dietary supplements, this paper reports the
      isolation of three new markers, namely, 1-O-(3'-methylbut-3'-enyl)-beta-D
      glucopyranose (1), 1-n-butyl-4-(5'-formyl-2'-furanyl)methyl succinate (2), and 4
      epi-borreriagenin (3), together with the known iridoid glycosides asperulosidic
      acid (4) and deacetylasperulosidic acid (5) and a mixture of 1-n-butyl-4-methyl-2
      hydroxysuccinate (6a) and 1-n-butyl-4-methyl-3-hydroxysuccinate (6b), as well as
      a mixture of alpha- and beta-glucopyranose from noni fruit juice obtained from
      Puerto Rico. The structures of compounds were based on 1H and 13C NMR, mainly 2D
      NMR COSY, HMQC, HMBC, and NOESY experiments, and HRMS. Furthermore, samples from
      fresh-squeezed noni fruit juice from Japan revealed the presence of scopoletin
      (7), in addition to compounds 1-6, indicating no significant differences in the
      marker constituents of noni collected from Atlantic and Pacific regions.

PMID- 16910737
TI  - Partitioning and inhibition of lipid oxidation in mechanically separated turkey
      by components of cranberry press cake.
AB  - Extracts from cranberry press cakes were prepared either using ethanol or an
      ethyl acetate-acetone mixture. The press cake extracts were compared with
      extracts from cranberry juice powder (CJP), prepared using chloroform:methanol
      (1:1), for their ability to inhibit lipid oxidation in mechanically separated
      turkey (MST). Because of the susceptibility of muscle membrane lipids to
      oxidation, the ability of quercetin in the extracts to partition between the
      aqueous and the membrane phases was studied. Membrane suspensions were prepared
      from MST. Partitioning of quercetin was quantified using high-performance liquid
      chromatography. Oxidation was studied by measuring thiobarbituric acid reactive
      substances and lipid peroxides. The effectiveness of the extracts to inhibit
      lipid oxidation was CJP extract > ethyl acetate extract of press cake > or =
      ethanol extract of press cake. The amount of quercetin in the extracts and the
      amount of quercetin that partitioned into the membranes followed the same order.
      However, the total phenolic content of the extracts did not follow the same order
      as that of inhibitory power. The phenolic content of the extracts decreased,
      ethyl acetate extract > ethanol extract of press cake > or = chloroform extract
      of CJP. Irrespective of the extraction method, around 78% quercetin from the
      extracts partitioned into the membranes. It could be concluded that increasing
      the amount of quercetin in the press cake extracts increases the ability of the
      extracts to inhibit lipid oxidation in MST. Hence, a proper choice of solvents
      and extraction method, which would increase the amount of quercetin in the press
      cake extracts, might increase the antioxidant potential of the extracts and hence
      their economic value.

PMID- 16910738
TI  - Structural identification of dehydrotriferulic and dehydrotetraferulic acids
      isolated from insoluble maize bran fiber.
AB  - Two new dehydrotriferulic acids and two dehydrotetraferulic acids were isolated
      from saponified maize bran insoluble fiber using size exclusion chromatography on
      Bio-Beads S-X3 followed by Sephadex LH-20 chromatography and semipreparative
      phenyl-hexyl reversed phase high-performance liquid chromatography. On the basis
      of UV spectroscopy, mass spectrometry, and one- and two-dimensional NMR
      experiments, the structures were identified as 8-5(noncyclic)/5-5
      dehydrotriferulic acid, 8-8(tetrahydrofuran)/5-5-dehydrotriferulic acid, and 4-O
      8/5-5/8-O-4-dehydrotetraferulic acid. The second tetramer was tentatively
      identified as 4-O-8/5-5/8-5(noncyclic)-dehydrotetraferulic acid. Compounds
      containing an 8-5(noncyclic)-coupled dimeric unit probably do not exist in planta
      but are formed from their phenylcoumaran precursors containing an 8-5(cyclic)
      coupled dimeric unit during saponification. The presented dehydrotrimers are the
      first dehydrotriferulates that do not contain an 8-O-4-coupled dimeric unit. The
      ferulate dehydrotetramers that are reported for the first time are presumed, like
      the dimers and trimers, to cross-link polysaccharides in the plant. Because both
      tetramers contain a 5-5/8-O-4-dehydrotriferulate moiety, the predominant
      dehydrotrimer in maize bran, it is not possible to deduce whether tetramers are
      formed by coupling of a fourth unit to a preformed dehydrotriferulate or by 5-5
      coupling of preformed 8-O-4- and 8-5-dehydrodiferulates. Nevertheless, such
      compounds document expanded roles for ferulates in cross-linking polysaccharides
      in plant cell walls.

PMID- 16910739
TI  - Effects of protein composition and enzymatic activity on formation and properties
      of potato protein stabilized emulsions.
AB  - In the present study emulsions were made with various potato protein
      preparations, which varied in protease inhibitor and patatin content. These
      emulsions were characterized with respect to average droplet size, plateau
      surface excess, and the occurrence of droplet aggregation. Droplet aggregation
      occurred only with potato protein preparations that contained a substantial
      amount of protease inhibitors and could be prevented only at pH 3. The average
      droplet size of the emulsions made with potato proteins appeared to be related to
      the patatin content of the preparation used. Average droplet size was found to be
      dominated by the patatin-catalyzed lipolytic release of surface active fatty
      acids and monoglycerides from the tricaprylin oil phase during the emulsification
      process. Addition of monoglycerides and especially fatty acids, at concentrations
      representative of those during emulsification, was shown to cause a stronger and
      much faster decrease of the interfacial tension than that with protein alone and
      to result in a drastic decrease in droplet size. The patatin used was shown to
      have a lipolytic activity of 820 units/g with emulsified tricaprylin as the
      substrate. Because of the droplet aggregating properties of the protease
      inhibitors, the patatin-rich potato preparations seem to be the most promising
      for food emulsion applications over a broad pH range, provided the lipolytic
      activity can be diminished or circumvented.

PMID- 16910740
TI  - Soyasaponins resist extrusion cooking and are not degraded during gut passage in
      Atlantic salmon (Salmo salar L.).
AB  - The stability of soyasaponins in fish feed formulations was investigated. The
      level of soyasaponin Ab, Bb, Bc, Ba-2,3-dihydro-2,5-dihydroxy-6-methyl-4H-pyran-4
      one (Ba-DDMP), Bb-DDMP, and Bc-DDMP was quantified in 15 samples of defatted
      soybean meal, two full fat soybean meals, and two soybean protein concentrates by
      reverse phase high-performance liquid chromatography. The total level of saponins
      in the 15 samples of commercial defatted soybean meal ranged from 4.8-6.8
      micromol/g (5.1-7.0 g/kg). The two full fat meals contained 4.4 and 4.7
      micromol/g whereas no saponins could be detected in the alcohol-extracted soybean
      protein concentrates. Fifteen batches of fish feed containing 20% defatted
      soybean meal were produced by twin-screw extrusion from the 15 different samples
      of defatted soybean meal. Extrusion did not reduce the total level of group B
      saponins, but the ratio between DDMP-conjugated group B saponins and non-DDMP
      conjugated group B saponins was slightly reduced. A soybean-containing diet was
      fed to seawater adapted Atlantic salmon for 9 weeks. Yttrium oxide was included
      in the feed as an inert marker in order to estimate the disappearance of saponins
      during gut passage. High levels of intact non-DDMP-conjugated group B
      soyasaponins were found in feces whereas only low levels of DDMP-conjugated
      saponins could be detected. The overall disappearance of saponins was close to
      zero, and the concentration of intact saponins in dry feces reached levels
      several fold higher than dietary levels. The present work demonstrates that non
      DDMP-conjugated group B soyasaponins resist extrusion cooking and remain intact
      during gut passage in Atlantic salmon. The latter is contrary to earlier findings
      in endothermic animals.

PMID- 16910741
TI  - Effects of capsaicin, dihydrocapsaicin, and curcumin on copper-induced oxidation
      of human serum lipids.
AB  - The oxidation of low-density lipoprotein (LDL) is believed to be the initiating
      factor for the development and progression of atherosclerosis. The active
      ingredients of spices such as chili and turmeric (capsaicin and curcumin,
      respectively) have been shown to reduce the susceptibility of LDL to oxidation.
      One of the techniques used to study the oxidation of LDL is to isolate LDL and
      subject it to metal-induced (copper or iron) oxidation. However, whole serum may
      represent a closer situation to in vivo conditions than using isolated LDL. We
      investigated the effects of different concentrations (0.1-3 microM) of capsaicin,
      dihydrocapsaicin, and curcumin on copper-induced oxidation of serum lipoproteins.
      The lag time (before initiation of oxidation) and rate of oxidation (slope of
      propagation phase) were calculated. The lag time increased, and the rate of
      oxidation decreased with increasing concentrations of the tested antioxidants (p
      < 0.05). A 50% increase in lag time (from control) was observed at concentrations
      between 0.5 and 0.7 microM for capsaicin, dihydrocapsaicin, and curcumin. This
      study shows that oxidation of serum lipids is reduced by capsaicinoids and
      curcumin in a concentration-dependent manner.

PMID- 16910742
TI  - Nonabsorbable dietary fat enhances disposal of 2,2',4,4'-tetrabromodiphenyl ether
      in rats through interruption of enterohepatic circulation.
AB  - Polybrominated diphenyl ethers are lipophilic persistent organic pollutants
      (POPs), which accumulate in the environment, leading to human exposure. The
      compounds exert a negative impact on human health. Strategies to prevent or
      diminish their accumulation in humans are required. We investigated in rats
      whether the disposal rate of 14C-labeled tetrabromodiphenyl ether (BDE-47) could
      be enhanced by increasing fecal fat excretion through dietary treatment with
      nonabsorbable fat (sucrose polyester, SPE). As compared to control rats, SPE
      treatment increased fecal excretion rates of fat (+188%, p < 0.05) and 14C-BDE-47
      (+291%, p < 0.05). On the basis of biliary secretion and fecal excretion rates of
      14C-BDE-47, SPE effectively inhibited the enterohepatic circulation of 14C-BDE
      47. In conclusion, dietary supplementation of nonabsorbable fat can enhance
      excretion of hydrophobic POPs by interruption of their enterohepatic circulation.
      Our data indicate that this strategy could decrease concentrations of hydrophobic
      POPs in the human body and thereby their impact on human health.

PMID- 16910743
TI  - Thermal degradation of the Fusarium mycotoxin deoxynivalenol.
AB  - Deoxynivalenol (DON) is a toxic secondary metabolite produced by molds of the
      Fusarium genus, which are able to infect cereal crops in the field. Concerning
      its rate of occurrence and mean concentration, DON is one of the most important
      mycotoxins in cereal commodities. Its toxic effects range from causing diarrhea,
      vomiting, and gastro-intestinal inflammation to noncompetitive inhibition of the
      biosynthesis of proteins in eukaryotic cells. To study the stability of DON under
      food-processing conditions such as cooking or baking, we performed model heating
      experiments and screened the residue for degradation products. Heating of DON and
      3-acetyldeoxynivalenol (3-AcDON), especially under alkaline conditions, gave a
      mixture of compounds, which were isolated and structurally elucidated by NMR and
      MS experiments. Three of these compounds were already known (norDON A, norDON B,
      and norDON C), while four were new and named 9-hydroxymethyl DON lactone, norDON
      D, norDON E, and norDON F. The significance of the DON degradation products was
      checked by analyzing commercially available food samples. norDON A, B, and C were
      detected in 29-66% of the samples in mean concentrations ranging from 3 to 15
      microg/kg. Furthermore, cell culture experiments using IHKE cells showed that the
      compounds that were detected in food samples are less cytotoxic in the formazan
      dye cytotoxicity assay compared to DON. Whereas DON revealed a median effective
      concentration (EC50) at 1.1 micromol/L, all other compounds did not show any
      significant effect up to 100 micromol/L. These findings indicate that the
      degradation of DON under thermal treatment might reduce the toxicity of DON
      contaminated food.

PMID- 16910744
TI  - Effect of pH on binding of mutagenic heterocyclic amines by the natural
      biopolymer poly(gamma-glutamic acid).
AB  - Poly(gamma-glutamic acid) (gamma-PGA), a nontoxic and biodegradable macropolymer,
      was evaluated for its efficiency in binding three mutagenic heterocyclic amines
      (HAs), 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), 2-amino-3,4,8
      trimethylimidazo[4,5-f]quinoxaline (4,8-DiMeIQx), and 3-amino-1-methyl-5H
      pyrido[4,3-b]indole (Trp-p-2), as affected by pH in a batch mode. The maximum HA
      sorption was attained for pH 3-7 and decreased sharply for pH less than 3.
      Binding isotherms obtained at pH 2.5 and 5.5 showed different isotherm shapes
      that belong to S and L types, respectively. The isotherm data at pH 2.5 were well
      described by a linear form of the Langmuir equation, while at pH 5.5 it showed
      two distinct curves, which were precisely fitted as multiple Langmuir curves. The
      deviation of linearity in Scatchard plot proved the multisite HA sorption. The
      Brunauer-Emmett-Teller equation also fitted better to isotherm data at pH 5.5,
      suggesting a multisite sorption caused by multimolecular HA layers on gamma-PGA.
      High HA sorption levels of 1250, 667, and 1429 mg/g at pH 2.5 and 1429, 909, and
      1667 mg/g at pH 5.5 were observed for MeIQ, 4,8-DiMeIQx, and Trp-p-2,
      respectively. Among the HAs studied, the sorption capacity correlated directly
      with hydrophobicity of HAs and inversely with the number of methyl groups in HA
      molecules. The plausible binding mechanism of HAs on gamma-PGA may include a
      combination of hydrophobic, hydrogen-bonding, ionic, and dipole-dipole
      interactions.

PMID- 16910745
TI  - Fate of ochratoxin A during vinification of Semillon and Shiraz grapes.
AB  - Semillon and Shiraz grapes containing ochratoxin A (OA) were obtained by
      inoculation of bunches on the vine with Aspergillus carbonarius. Citric acid
      content was greater in the inoculated grapes than in healthy grapes. Samples were
      collected throughout vinification of these grapes and the OA content was
      quantified using a stable isotope dilution liquid chromatographic-tandem mass
      spectrometric method. The mass of processed and waste streams during vinification
      was also noted. Reduction in the amount of OA in juice and wine occurred at every
      solid-liquid separation stage. The OA concentration (microg/kg) in white and red
      wine after racking was 4% and 9%, respectively, of that in crushed grapes. This
      corresponds to 1% and 6% of the total OA content that was initially present in
      the inoculated grapes. The OA content was divided between solid and liquid phases
      at each stage of vinification. OA did not appear to be transformed either
      chemically or biologically by yeast during fermentation, rather was discarded
      with the marc, juice lees, and gross lees.

PMID- 16910746
TI  - Optimizing assurance: the risk regulation system in relationships.
AB  - A model of risk regulation is proposed to explain how people balance the goal of
      seeking closeness to a romantic partner against the opposing goal of minimizing
      the likelihood and pain of rejection. The central premise is that confidence in a
      partner's positive regard and caring allows people to risk seeking dependence and
      connectedness. The risk regulation system consists of 3 interconnected "if--then"
      contingency rules, 1 cognitive, 1 affective, and 1 behavioral. The authors
      describe how general perceptions of a partner's regard structure the sensitivity
      of these 3 "if--then" rules in risky relationship situations. The authors then
      describe the consequences of such situated "if--then" rules for relationship well
      being and conclude by integrating other theoretical perspectives and outlining
      future research directions.

PMID- 16910748
TI  - Associative and propositional processes in evaluation: an integrative review of
      implicit and explicit attitude change.
AB  - A central theme in recent research on attitudes is the distinction between
      deliberate, "explicit" attitudes and automatic, "implicit" attitudes. The present
      article provides an integrative review of the available evidence on implicit and
      explicit attitude change that is guided by a distinction between associative and
      propositional processes. Whereas associative processes are characterized by mere
      activation independent of subjective truth or falsity, propositional reasoning is
      concerned with the validation of evaluations and beliefs. The proposed
      associative-propositional evaluation (APE) model makes specific assumptions about
      the mutual interplay of the 2 processes, implying several mechanisms that lead to
      symmetric or asymmetric changes in implicit and explicit attitudes. The model
      integrates a broad range of empirical evidence and implies several new
      predictions for implicit and explicit attitude change.

PMID- 16910747
TI  - A meta-analytic review of obesity prevention programs for children and
      adolescents: the skinny on interventions that work.
AB  - This meta-analytic review summarizes obesity prevention programs and their
      effects and investigates participant, intervention, delivery, and design features
      associated with larger effects. A literature search identified 64 prevention
      programs seeking to produce weight gain prevention effects, of which 21% produced
      significant prevention effects that were typically pre- to post effects. Larger
      effects emerged for programs that targeted children and adolescents (vs.
      preadolescents) and females, programs that were relatively brief, programs that
      solely targeted weight control versus other health behaviors (e.g., smoking),
      programs evaluated in pilot trials, and programs wherein participants must have
      self-selected into the intervention. Other factors, including mandated
      improvements in diet and exercise, sedentary behavior reduction, delivery by
      trained interventionists, and parental involvement, were not associated with
      significantly larger effects.

PMID- 16910749
TI  - Associating versus proposing or associating what we propose: comment on Gawronski
      and Bodenhausen (2006).
AB  - This commentary highlights the strengths of the associative-propositional
      evaluation model. It then describes problems in proposing a qualitative
      separation between propositional and associative processes. Propositional
      processes are instead described as associative. Propositions are ordered
      associations, whereas many other associations do not depend on the order of the
      involved elements. Implications of this alternative definition for the
      phenomenology of thought and for social psychology are discussed.

PMID- 16910750
TI  - Are associative and propositional processes qualitatively distinct? Comment on
      Gawronski and Bodenhausen (2006).
AB  - The authors comment on B. Gawronski and G. V. Bodenhausen's (2006) associative
      propositional evaluation model of implicit and explicit attitudes by examining
      the claims that (a) truth value is attached to propositions but not to
      associations; (b) pattern activation is qualitatively different from syllogistic
      structure of arguments; and (c) Pavlovian conditioning may be propositional,
      whereas evaluative conditioning is not. They conclude that despite surface
      dissimilarities between implicit and explicit attitudes both may be mediated by
      the same underlying process.

PMID- 16910751
TI  - A metacognitive approach to "implicit" and "explicit" evaluations: comment on
      Gawronski and Bodenhausen (2006).
AB  - A metacognitive model (MCM) is presented to describe how automatic (implicit) and
      deliberative (explicit) measures of attitudes respond to change attempts. The
      model assumes that contemporary implicit measures tap quick evaluative
      associations, whereas explicit measures also consider the perceived validity of
      these associations (and other factors). Change in explicit measures is greater
      than implicit measures when new evaluative associations are formed and old
      associations are rejected. Implicit measure change is greater than explicit when
      newly formed evaluative associations are rejected. When implicit and explicit
      evaluations conflict, implicit ambivalence can occur. The authors relate the MCM
      to the associative-propositional evaluation model and explain how the MCM builds
      on the attitude strength assumptions of the elaboration likelihood model of
      persuasion.

PMID- 16910753
TI  - Personality and aggressive behavior under provoking and neutral conditions: a
      meta-analytic review.
AB  - The authors conducted a comprehensive review to understand the relation between
      personality and aggressive behavior, under provoking and nonprovoking conditions.
      The qualitative review revealed that some personality variables influenced
      aggressive behavior under both neutral and provocation conditions, whereas others
      influenced aggressive behavior only under provocation. Studies that assessed
      personality variables and that directly measured aggressive behavior were
      included in the quantitative review. Analyses revealed that trait aggressiveness
      and trait irritability influenced aggressive behavior under both provoking and
      neutral conditions but that other personality variables (e.g., trait anger, Type
      A personality, dissipation-rumination) influenced aggressive behavior only under
      provoking conditions. The authors discuss possible relations between these
      patterns of aggressive behavior and the personality dimensions of Agreeableness
      and Neuroticism and consider implications for theories of aggression.

PMID- 16910754
TI  - Forming attitudes that predict future behavior: a meta-analysis of the attitude
      behavior relation.
AB  - A meta-analysis (k of conditions = 128; N = 4,598) examined the influence of
      factors present at the time an attitude is formed on the degree to which this
      attitude guides future behavior. The findings indicated that attitudes correlated
      with a future behavior more strongly when they were easy to recall (accessible)
      and stable over time. Because of increased accessibility, attitudes more strongly
      predicted future behavior when participants had direct experience with the
      attitude object and reported their attitudes frequently. Because of the resulting
      attitude stability, the attitude-behavior association was strongest when
      attitudes were confident, when participants formed their attitude on the basis of
      behavior-relevant information, and when they received or were induced to think
      about one- rather than two-sided information about the attitude object.

PMID- 16910755
TI  - Rethinking the total cost of care in AOM and ABS: The impact of improved
      diagnostic accuracy and antibiotic treatment where high efficacy and adherence
      are achievable.

PMID- 16910756
TI  - A review of recommended antibiotic therapies with impact on outcomes in acute
      otitis media and acute bacterial sinusitis.

PMID- 16910758
TI  - A computational model for free radicals transport in the microcirculation.
AB  - Nitric oxide (NO), superoxide (O(2)(-)), and peroxynitrite (ONOO(-)) interactions
      in pathophysiologic conditions such as cardiovascular disease, hypertension, and
      diabetes have been studied extensively in vivo and in vitro. A reduction in
      bioavailability of NO is a common event that is known as the endothelial
      dysfunction in these conditions. Despite intense investigation of NO biotransport
      and O(2)(-) and ONOO(-) biochemical interactions in vasculature, we have very
      little quantitative knowledge of distributions and concentrations of NO, O(2)(-),
      and ONOO(-) under normal physiologic and pathophysiologic conditions. Based on
      fundamental principles of mass balance, vessel geometry, and reaction kinetics,
      we developed a mathematical model of these free radicals transport in and around
      an arteriole during oxidative stress. We investigated the role of O(2)(-) and
      ONOO(-) in inactivating vasoactive NO. The model predictions include (a) NO
      interactions with oxygen, O(2)(-), and ONOO(-) have relatively little effect on
      the NO level in the vascular smooth muscle under physiologic conditions; (b)
      superoxide diffuses only a few microns from its source, whereas peroxynitrite
      diffuses over a larger distance; and (c) reduced superoxide dismutase levels
      significantly increase O(2)(-) and peroxynitrite concentrations and decrease NO
      concentration. Model results indicate that the reduced NO bioavailability and
      enhanced peroxynitrite formation may vary depending on the location of oxidative
      stress in the microcirculation, which occurs at diverse vascular cell locations
      in diabetes, aging, and cardiovascular diseases. The results will have
      significant implications for our understanding of these free radical interactions
      in physiologic and pathophysiologic conditions resulting from endothelial
      dysfunction.

PMID- 16910757
TI  - Effects of S-nitrosation on hemoglobin-induced microvascular damage.
AB  - Blood substitutes, such as diaspirin cross-linked hemoglobin (Hb), cause
      microvascular leakiness to macromolecules. Because of the potentially stabilizing
      effects of nitric acid (NO) on endothelium, experiments were performed to
      determine whether S-nitrosohemoglobin (SNO-Hb), a potential NO-donor Hb-based
      blood substitute, would not cause microvascular damage. Release of NO, or its
      metabolites, from the SNO-Hb was facilitated by addition of glutathione, which
      aids in the decomposition of S-nitrosothiols. In anesthetized rats, the
      mesenteric microvasculature was perfused with SNO-Hb with glutathione (six rats),
      SNO-Hb alone (six rats), or saline (eight rats) for 10 min, followed by
      fluorescein isothiocyanate (FITC)-albumin for 1 min, and finally fixed for
      epifluorescence microscopic examination. When comparing the SNO-Hb group with
      saline, both the numbers and areas of leaks were significantly increased [0.019
      +/- 0.003 (SEM) microm vs. 0.0030 +/- 0.0004 and 7.36 +/- 1.50 vs. 0.156 +/-
      0.035 (p < 0.005)]. With the addition of glutathione, leakage was still high
      (0.005 +/- 0.00005 microm and 5.086 +/- 0.064 microm) but decreased compared with
      SNO-Hb alone (p < 0.005). In conclusion, NO, or a related vasodilator, when
      released from SNO-Hb, significantly reduces but does not eliminate microvascular
      damage. Further improvements may result by S-nitrosating a more stable form of
      modified hemoglobin.

PMID- 16910759
TI  - Reactive oxygen species in the cerebral circulation: are they all bad?
AB  - Reactive oxygen species (ROS) are a diverse family of molecules generated by all
      cells. ROS may serve as important cell-signalling molecules in the cerebral
      circulation. Indeed, in contrast to systemic arteries, major products of
      superoxide metabolism, including hydrogen peroxide, are powerful cerebral
      vasodilators, raising the possibility that ROS represent important molecules for
      increasing local cerebral blood flow. Two major determinants of the overall
      effects of ROS on cerebrovascular tone are the rate of production of the parent
      molecule, superoxide, and its rate of metabolism by superoxide dismutases.
      Although the major enzymatic source of ROS in cerebral arteries has not been
      clarified, nicotinamide adenine dinucleotide phosphate, reduced form (NADPH)
      oxidases, along with cyclooxygenases and lipoxygenases, are probably the primary
      sources. In cerebral arteries, activation of NADPH-oxidase elicits both an
      increase in superoxide production and vasodilatation. The identity of the ROS
      molecule responsible for the vasodilator effects may be hydrogen peroxide,
      generated from the dismutation of superoxide. NADPH-oxidase activity and function
      appears to be profoundly greater in cerebral versus systemic arteries.
      Furthermore, NADPH-oxidase-derived ROS partly contribute to flow-dependent
      dilatation and may offset angiotensin II-induced constriction of cerebral
      arteries, consistent with the hypothesis that NADPH-oxidase-derived ROS may play
      a physiologic role in the control of cerebrovascular tone.

PMID- 16910760
TI  - Mechanosensitive production of reactive oxygen species in endothelial and smooth
      muscle cells: role in microvascular remodeling?
AB  - Changes in the hemodynamic environment (e.g., hypertension, increased blood
      flow/shear stress) are known to lead to vascular remodeling; however, the
      underlying mechanisms by which hemodynamic forces control gene expression in
      vascular cells are not yet completely understood. This review considers how
      mechanosensitive generation of reactive oxygen species (ROS) by NAD(P)H oxidases
      and other sources interacts with downstream signaling systems [including
      activation of nuclear factor kappa B (NF-kappaB) and AP-1] that modulate the
      phenotype of endothelial and smooth muscle cells, leading to vascular remodeling.
      We propose a model for an interaction between direct mechanosensitive ROS
      signaling and pathways activated by pressure-induced upregulation of prooxidant
      paracrine signaling mechanisms [local renin-angiotensin system, TNF-alpha-
      converting enzyme (TACE)/tumor necrosis factor alpha (TNF-alpha) system, and
      endothelin signaling].

PMID- 16910761
TI  - Adverse effects of reactive oxygen species on vascular reactivity in insulin
      resistance.
AB  - Insulin resistance (IR) has adverse effects on the reactivity of arteries and
      arterioles and promotes arterial hypertension and vascular occlusive diseases.
      Altered reactivity of resistance vessels occurs at both the endothelium and
      smooth-muscle levels. One major mechanism of vascular dysfunction with IR
      involves the augmented generation, availability, and/or actions of reactive
      oxygen species (ROS). Scavengers of ROS are able immediately to restore normal
      dilator responsiveness in arteries from IR animals. Other factors, such as
      increased importance of constrictor agents such as endothelin, also restrict
      normal dilator responses. The basis of ROS-mediated vascular dysfunction in IR
      may be secondary to underlying inflammatory processes throughout the arterial
      wall. Although ROS scavengers may be beneficial in the short term, prolonged
      treatments involving behavioral approaches, such as changes in diet, weight loss,
      and regular exercise, and pharmacological approaches, involving the use of
      insulin-sensitizing agents, inhibitors of the renin-angiotensin system, or
      administration of statins, appear to offer benefits against the detrimental
      vascular effects of IR. Nonetheless, the most effective approach appears to
      involve prevention of IR via adoption of a healthy lifestyle by young people.

PMID- 16910762
TI  - Microvascular responses to hypercholesterolemia: the interactions between innate
      and adaptive immune responses.
AB  - Hypercholesterolemia is recognized as one of the major risk factors in
      cardiovascular disease. It promotes the development of a proinflammatory
      phenotype in large vessels, in particular arteries, with disease. Cells of the
      innate and adaptive immune system are localized within atherosclerotic plaques
      and participate in the initiation and progression of plaque formation. It is now
      recognized that each segment of the microvasculature also experiences
      inflammation due to hypercholesterolemia, and that this occurs long before events
      in the large vessels. More recently, it is has been established that the innate
      and adaptive immune systems participate in the responses of postcapillary
      venules, and possibly arterioles, to elevated cholesterol levels, and that T
      lymphocytes may be one of the early cell types activated by hypercholesterolemia.
      These cells initiate a series of steps that lead to leukocyte accumulation in
      postcapillary venules and endothelial dysfunction in the arterioles. This review
      discusses the microvascular alterations induced by hypercholesterolemia, with
      particular attention paid to the roles of the innate and adaptive immune
      responses, and how these two systems may communicate to induce the microvascular
      inflammation.

PMID- 16910763
TI  - Dual role of VEGF-induced heme-oxygenase-1 in angiogenesis.
AB  - Heme-oxygenase-1 (HO-1) is an inducible cytoprotective molecule that displays
      antioxidant, antiapoptotic, and antiinflammatory effects. In addition, HO-1
      appears to have a complex role in angiogenesis. Recent in vivo studies report
      that vascular endothelial growth factor (VEGF) regulates HO-1 expression and
      activity in vascular endothelial cells (ECs) and that inhibition of HO-1
      abrogates VEGF-induced endothelial activation and subsequent angiogenesis, while
      promoting VEGF-induced monocyte recruitment and inflammatory angiogenesis. HO-1
      may also regulate the synthesis and activity of VEGF, resulting in a positive
      feedback loop. In contrast, HO-1 activity has the opposite effect on
      lipopolysaccharide-driven inflammatory angiogenesis, inhibiting leukocyte
      invasion and preventing subsequent angiogenesis. In this review, we summarize the
      current understanding of the role of HO-1 in angiogenesis. We conclude that
      further investigation, using targeted molecular approaches specifically to alter
      HO-1 activity, are required to develop our understanding of the role of HO-1 and
      its products, carbon monoxide, biliverdin, bilirubin, and free iron in
      angiogenesis. We propose that during chronic inflammation, HO-1 has two roles,
      first an antiinflammatory action inhibiting leukocyte infiltration, and second,
      promotion of VEGF-driven noninflammatory angiogenesis, which facilitates tissue
      repair. Additional studies will help determine whether modulating the activity of
      HO-1 and/or its products has therapeutic potential in chronic inflammatory dise.

PMID- 16910764
TI  - Redox control of red blood cell biology: the red blood cell as a target and
      source of prooxidant species.
AB  - Red blood cells may exert both an antioxidant and a prooxidant activity. The
      first is exerted in physiologic conditions, whereas the second can be detected in
      several human pathologies. These opposite characteristics can depend on the
      environmental milieu as well as on intrinsic alterations. Both these aspects are
      summarized in this brief review that takes into account the possible implications
      of redox-associated alterations of red blood cells in determining their function
      and fate.

PMID- 16910765
TI  - The red blood cell as a biosensor for monitoring oxidative imbalance in chronic
      obstructive pulmonary disease: an ex vivo and in vitro study.
AB  - Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity in
      Western countries. The increased oxidative stress, caused by the release of
      reactive oxygen and nitrogen species (ROS/RNS) from inflammatory airways cells,
      contributes to the pathogenesis of the disease. The aim of the present study was
      to evaluate (a) whether the oxidative imbalance can lead to specific alterations
      of red blood cells (RBCs) from stable COPD patients; (b) whether treatment with N
      acetyl-cysteine (NAC), in widespread use as mucolytic agent in clinical practice,
      can counteract these effects; and (c) whether an in vitro model represented by
      the exposure of RBC to ROS/RNS could mimic the in vivo situation. The results
      obtained clearly indicated that the RBC integrity and function are similarly
      altered in COPD patients and in ROS/RNS in vitro-treated samples and that NAC
      administration was capable of counteracting RBC oxidative modifications both in
      vivo, as detected by clinical and laboratory evaluations, and in vitro.
      Altogether these results point to RBC oxidative modifications as valuable
      bioindicators in the clinical management of COPD and indicate that in vitro RBC
      exposure to ROS/RNS as a useful tool in experimental studies aimed at the
      comprehension of the pathogenic mechanisms of the redox-associated diseases.

PMID- 16910766
TI  - Mechanisms and significance of eryptosis.
AB  - Suicidal death of erythrocytes (eryptosis) is characterized by cell shrinkage,
      membrane blebbing, activation of proteases, and phosphatidylserine exposure at
      the outer membrane leaflet. Exposed phosphatidylserine is recognized by
      macrophages that engulf and degrade the affected cells. Eryptosis is triggered by
      erythrocyte injury after several stressors, including oxidative stress. Besides
      caspase activation after oxidative stress, two signaling pathways converge to
      trigger eryptosis: (a) formation of prostaglandin E(2) leads to activation of
      Ca(2+)-permeable cation channels, and (b) the phospholipase A(2)-mediated release
      of platelet-activating factor activates a sphingomyelinase, leading to formation
      of ceramide. Increased cytosolic Ca(2+) activity and enhanced ceramide levels
      lead to membrane scrambling with subsequent phosphatidylserine exposure.
      Moreover, Ca(2+) activates Ca(2+)-sensitive K(2+) channels, leading to cellular
      KCl loss and cell shrinkage. In addition, Ca(2+) stimulates the protease calpain,
      resulting in degradation of the cytoskeleton. Eryptosis is inhibited by
      erythropoietin, which thus extends the life span of circulating erythrocytes.
      Eryptosis may be a mechanism of defective erythrocytes to escape hemolysis.
      Conversely, excessive eryptosis favors the development of anemia. Conditions with
      excessive eryptosis include iron deficiency, lead or mercury intoxication, sickle
      cell anemia, thalassemia, glucose 6- phosphate dehydrogenase deficiency, malaria,
      and infection with hemolysin-forming pathogens.

PMID- 16910767
TI  - Nitric oxide redox reactions and red cell biology.
AB  - Three hypotheses explain a role for red blood cells (RBCs) in delivering NO to
      the vasculature: (a) "the SNOHb hypothesis" involves the uptake of NO by RBCs
      with NO transferred from the heme to the beta-93 thiol in the R quaternary
      conformation, followed by the release to membrane thiols in the T quaternary
      conformation; and (b and c) "the nitrite hypotheses" bypass the intrinsic
      difficulties of transporting the highly reactive NO, by reutilizing the nitrite
      formed when NO reacts with oxygen. Deoxyhemoglobin reduces this nitrite back to
      NO. The distinction between the two nitrite mechanisms depends on the importance
      of intermediate species formed during nitrite reduction. Without bioactive
      intermediates, the NO must be immediately released to avoid binding to
      deoxyhemoglobin. The "nitrite intermediate hypothesis" enables the RBCs to store
      a pool of potentially bioactive NO until it is released from the cell. In this
      review, we critically compare these different proposals for the
      transport/delivery of NO by RBCs. We also compare the redox properties in the
      RBCs associated with NO with the redox properties associated with oxygen.

PMID- 16910768
TI  - Redox imbalance, macrocytosis, and RBC homeostasis.
AB  - The erythrocyte represents a major component of the antioxidant capacity of the
      blood through the enzymes contained in the cell, the glutathione system, and the
      low-molecular-weight antioxidants of the erythrocyte membrane. A further major
      red blood cell contribution is in regenerating consumed redox equivalents via the
      oxidative pentose phosphate pathway and glutathione reductase. Moreover, its
      extracellular antioxidant capacity, its mobility, and the existence of reducing
      equivalents far in excess of its normal requirements make erythrocytes function
      as an effective oxidative sink in the organism. That is why red blood cell
      metabolism and homeostasis strongly affect the antioxidant properties of the
      whole body. Conversely, the relation between macrocytosis and oxidative stress
      has not been fully delineated. Reviewing the mechanisms involved in red blood
      cell homeostasis in cases of redox imbalance is crucial in identification of
      factors that could potentially improve erythrocyte survival and defense against
      oxidant damage.

PMID- 16910769
TI  - SOD2-deficiency sideroblastic anemia and red blood cell oxidative stress.
AB  - Iron overload is a feature of an array of human disorders such as sideroblastic
      anemias, a heterogeneous group of erythropoietic disorders without identified
      cause in most cases. However, sideroblastic anemias appear to result from a
      disturbance at the interface between mitochondrial function and iron metabolism.
      A defining feature is excessive iron deposition within mitochondria of developing
      red cells, the consequences of which are an increase in cellular free radicals
      production, increased damage to proteins, and reduced cell survival. Because of
      its mitochondrial location, superoxide dismutase (SOD2) is the principal defense
      against the toxicity of superoxide anions generated by the oxidative
      phosphorylation. We have used hematopoietic stem cell transplantation to study
      blood cells lacking SOD2. We became interested in the role SOD2 plays in the
      metabolism of superoxide anions during erythroid development, as anemia is the
      major phenotype in transplanted animals. Our exploration of this model suggests
      that oxidative stress-and in particular, mitochondrial- derived oxidants-plays an
      important role in the pathogenesis of the human disorder, sideroblastic anemia.
      Here we review the relation between mitochondrial dysfunction and sideroblastic
      anemia, describe several methods for assessing oxidative damage to mature or
      developing red cells, present data on, and discuss the potential of antioxidant
      therapy for this disorder.

PMID- 16910770
TI  - Thioredoxin networks in the malarial parasite Plasmodium falciparum.
AB  - The intraerythrocytic protozoan parasite Plasmodium falciparum is responsible for
      more than 500 million clinical cases of tropical malaria annually. Although
      exposed to high fluxes of reactive oxygen species, Plasmodium lacks the
      antioxidant enzymes catalase and glutathione peroxidase. Thus, the parasite
      depends on the antioxidant capacity of its host cell and its own peroxidases.
      These are fuelled by the thioredoxin system and are considered to represent the
      major defense line against peroxides. Five peroxidases that act in different
      compartments have been described in P. falciparum. They include two typical 2-Cys
      peroxiredoxins (Prx), a 1-Cys Prx, the so-called antioxidant protein (AOP), which
      is a further Prx acting on the basis of a 1-Cys mechanism, and a glutathione
      peroxidase-like thioredoxin peroxidase. Because of their central function in
      redox regulation and antioxidant defense, some of these proteins might represent
      highly interesting targets for structure-based drug development. In this article
      we summarize the present knowledge on the thioredoxin and peroxiredoxin
      metabolism in malaria parasitized red blood cells. We furthermore report novel
      data on the biochemical and kinetic characterization of different thioredoxins,
      of AOP, and of the classic 1-Cys peroxiredoxin of P. falciparum.

PMID- 16910771
TI  - Plasma membrane oxidoreductases: effects on erythrocyte metabolism and redox
      homeostasis.
AB  - Plasma membrane oxidoreductases (PMORs) have been found in the membranes of all
      cells. These systems have been studied extensively in the human erythrocyte, so
      much is known about their activity and effect on erythrocyte cellular
      functioning. PMORs have been shown to be involved in a number of events
      associated with cell growth and function in other cell lines, but perhaps their
      most important role, especially in the nucleus- free mature erythrocyte, is as a
      redox sensor. The PMOR reduces extracellular oxidants by using the reducing power
      of intracellular antioxidants, making the cell metabolism respond to changes in
      the local redox environment. Thus, the activity of the PMOR is closely linked to
      the metabolic status of the erythrocyte. The main intracellular reductant for
      this system is ascorbic acid; however, the cell must also have the ability to
      supply NADH for full activity. Nuclear magnetic resonance studies on the effects
      of extracellular oxidants on intracellular metabolism have increased our
      knowledge of the intimate link between PMOR activity and metabolism, and these
      studies are reviewed here in detail.

PMID- 16910772
TI  - Redox signaling in cancer biology.
AB  - Over the last three decades, it is has become increasing clear that intracellular
      signaling pathways are activated via changes in intracellular metabolic
      oxidation/reduction (redox) reactions involving reactive oxygen species (ROS;
      i.e., superoxide and hydrogen peroxide). The initial proposals hypothesized that
      signaling through metabolic oxidation/reduction (redox) reactions involving ROS
      could contribute to carcinogenesis and progression to malignancy. Strong evidence
      for this hypothesis was obtained from studies showing that environmental insults
      (i.e., ionizing radiation) as well as xenobiotics (i.e., polycyclic aromatic
      hydrocarbons and phorbol esters) capable of inducing steady-state increases in
      free radical production and ROS could act as both initiators and promoters of
      carcinogenesis. This Forum is directed at understanding possible redox signaling
      mechanisms governing cellular radiation response, tumor growth, and response to
      therapy, as well as the role of nitric oxide in cancer biology.

PMID- 16910773
TI  - Normal human fibroblasts exposed to high- or low-dose ionizing radiation:
      differential effects on mitochondrial protein import and membrane potential.
AB  - How oxidative metabolism modulates effects of ionizing radiation is incompletely
      understood. Because mitochondria participate in oxidative metabolism, we
      investigated the modulation of mitochondrial protein import and membrane
      potential (DeltaPsi) in irradiated cells. Our data show that effects at low dose
      cannot be predicted from effects at high dose. When density-inhibited normal
      human fibroblasts were exposed to a toxic dose of 4 Gy, protein import into
      mitochondria isolated from these cells was decreased. In contrast, protein import
      into mitochondria isolated from low-dose-irradiated (10 cGy) cells was enhanced,
      suggesting that mitochondria may play a crucial role in low-dose-induced adaptive
      responses. At high dose, import defects were not solely due to changes in
      mitochondrial DeltaPsi, and modulation of import was not tightly linked to the
      cellular capacity to repair radiation damage. Another striking observation is
      that in proliferating nonirradiated cells, mitochondrial protein import and
      DeltaPsi were regulated in a cell cycle-dependent manner, being lower in S phase
      than in G (1). Interestingly, when quiescent G (0)/G (1) phase cells exposed to
      high-dose radiation were stimulated to proliferate, events associated with S
      phase, but not G (1), significantly affected import. The strategy described here
      may serve as novel end points to study radiation-induced effects.

PMID- 16910774
TI  - Radiation-induced changes in gene-expression profiles for the SCC VII tumor cells
      grown in vitro and in vivo.
AB  - SCCVII tumor cells that grow in vitro or in vivo as a solid tumor were used to
      compare and contrast geneexpression profiles with or without exposure to two
      doses of ionizing radiation. Exponentially growing SCCVII cell cultures and
      tumors (1 cm diameter) were treated with 0, 2, or 10 Gy, and RNA was collected 1,
      3, 6, 12, and 24 h after treatment. Growth under in vitro conditions increased
      the expression of genes associated with the unfolded protein response (UPR)
      including ATF4, Ero-1 like, and cystathionase. Growth in vivo indicated that the
      HIF-1a genes were not upregulated, whereas genes such as hemoglobin alpha and
      crystallin alpha B were significantly upregulated. Ninety genes of 16K were found
      to be significantly modulated under either growth condition by radiation
      treatment. Gene expression was not dose dependent. Sixty percent of these genes
      exhibited similar modulation under both in vitro and in vivo conditions; however,
      29% of the genes were modulated by radiation under in vivo conditions only. Gene
      expression profiles for the same tumor cells can differ, dependent on growth
      conditions, underscoring the influence that the tumor microenvironment exerts on
      gene expression for both growth of solid tumors and their response to radiation
      treatment.

PMID- 16910775
TI  - Mn-superoxide dismutase overexpression enhances G2 accumulation and
      radioresistance in human oral squamous carcinoma cells.
AB  - This study investigates the hypothesis that Mn-superoxide dismutase (MnSOD)
      influences cancer cell radiosensitivity by regulating the G(2)-checkpoint
      pathway. Human oral squamous carcinoma cells (SCC25) stably overexpressing MnSOD
      were irradiated (6 Gy) and assayed for cell survival, cell-cycle phase
      distributions, and bromodeoxyuridine (BrdU) pulse-chase flow-cytometric
      measurements of cell-cycle phase transits. Electron paramagnetic resonance (EPR)
      spectroscopy was used to measure steady-state levels of oxygen-centered free
      radicals. Glutathione and glutathione disulfide levels were used as indicators of
      changes in the intracellular redox state. MnSOD overexpression increased
      radioresistance threefold to fourfold; this increase was associated with twofold
      to threefold increases in radiation-induced G(2) accumulation. BrdU pulse-chase
      and flow-cytometric measurements of the percentage of G(1) and relative movement
      showed no significant changes in G(1) and S transits; however, the percentage of
      G(2) cells and BrdU-positive cells showed delayed G(2)+M transits in MnSOD
      overexpressing irradiated cells. The steady-state levels of oxygen-centered free
      radicals were not significantly different in vector compared with MnSOD
      overexpressing cells, suggesting that the free radical generation is essentially
      similar. MnSOD overexpression did prevent radiation-induced decreases in total
      glutathione content, which correlated with radioresistance and enhanced G(2)
      accumulation. These results support the hypothesis that a "metabolic redox
      response" to IR exposure regulates radiosensitivity by altering radiation-induced
      G(2) accumulation.

PMID- 16910777
TI  - Manganese superoxide dismutase protects from TNF-alpha-induced apoptosis by
      increasing the steady-state production of H2O2.
AB  - Manganese superoxide dismutase (SOD2) has been well established to be essential
      for protection from a variety of apoptotic stimuli. Here we demonstrate that the
      antiapoptotic effects of SOD2 are attributed to its ability to generate H(2)O(2)
      and that its efficient removal resensitizes cells to tumor necrosis factor (TNF)
      alpha-induced apoptosis. SOD2 overexpression in HT-1080 cells leads to a decrease
      in the fluorescence of the superoxidesensitive fluorophore, dihydroethidium, and
      a concomitant increase in oxidation of the H2O2-sensitive dye,
      dichlorodihydrofluorescein diacetate (DCFDA). The rate of aminotriazole-inhibited
      catalase activity also was increased when SOD2 is overexpressed and reflects a
      1.6-fold increase in the steady-state production of H(2)O(2). The increase in
      H(2)O(2) was associated with decreased sensitivity to TNF-alpha-mediated
      apoptosis, as measured by monitoring the loss of mitochondrial membrane potential
      (MMP), caspase activation, poly-ADP ribose polymerase (PARP) cleavage, and
      accumulation of hypodiploid DNA content. Both the increase in H2O2 and resistance
      to TNF-mediated apoptosis were reversed by coexpression of catalase. The lipid
      hydroperoxide scavengers, beta-hydroxytoluene and trolox, and the iron chelator,
      desferroxamine, showed partial recovery of TNF-induced apoptosis. These findings
      indicate that increases in the intracellular steady-state production of H(2)O(2)
      by SOD2 can block the activation of key processes fundamental to the process of
      programmed cell death.

PMID- 16910776
TI  - Enzymatic activity is necessary for the tumor-suppressive effects of MnSOD.
AB  - The antioxidant protein manganese-containing superoxide dismutase (MnSOD) has
      been found to be a new type of tumor-suppressor protein. Overexpression of the
      cDNA for this gene in various types of cancer via plasmid transfection or
      adenovirus transduction leads to growth suppression both in vitro and in vivo.
      The growth-suppressive effect of MnSOD overexpression has been presumed to be due
      to the enzymatic activity of the MnSOD protein, but could be due to a number of
      other mechanisms, including a regulatory effect of the RNA or protein produced.
      To examine this question, we used site-directed mutagenesis to produce a mutant
      form of human MnSOD that has a leucine at amino acid 26 in the active site rather
      than the usual histidine. We demonstrate that plasmid transfection or adenoviral
      transduction of this mutant MnSOD cDNA leads to a large increase in
      immunoreactive MnSOD protein, but little or no increase in enzymatic activity. In
      contrast, overexpression of wild-type MnSOD leads to cells with both increased
      MnSOD protein and activity. Overexpression of wild-type, but not mutant, MnSOD
      leads to decreased plating efficiency and growth. These results clearly
      demonstrate that the tumor-suppressive effect of MnSOD protein is largely due to
      its enzymatic activity.

PMID- 16910778
TI  - Inactivation of primary antioxidant enzymes in mouse keratinocytes by
      photodynamically generated singlet oxygen.
AB  - Cellular antioxidant enzymes protect against damage caused by exposure to
      endogenous or exogenous prooxidants. Singlet oxygen ((1)O(2)) is a reactive form
      of oxygen that can be produced in vivo either in normal and pathophysiologic
      conditions or by photosensitizing chemicals, as during photodynamic treatment. We
      hypothesized that photodynamically generated (1)O(2) would decrease the enzymatic
      activities of cellular antioxidants. To test this hypothesis, we treated cultured
      mouse epidermal keratinocytes with the photosensitizer Photofrin plus visible
      light to produce (1)O(2), and then measured CuZnSOD, MnSOD, and catalase
      activities with both ingel and spectrophotometric enzyme activity assays. Our
      results demonstrated that the enzymatic activities of cellular CuZnSOD, MnSOD,
      and catalase were significantly decreased after keratinocytes were treated with
      Photofrin plus visible light. By contrast, the enzymatic activities of cellular
      CuZnSOD, MnSOD, and catalase were unaffected in control cells treated with
      Photofrin only or visible light only. Despite the decreased levels of enzymatic
      activities, the protein levels of all three primary antioxidant enzymes remained
      constant after photodynamic treatment, as determined by Western blotting. L
      Histidine, a (1)O(2) quencher, protected against the inactivation of cellular
      CuZnSOD, MnSOD, and catalase enzymes induced by photodynamically generated
      (1)O(2). The conclusion from these experiments is that the primary cellular
      antioxidant enzymes CuZnSOD, MnSOD, and catalase can be inactivated by
      photodynamically generated (1)O(2) in nucleated mammalian cells. These findings
      may be useful in the future development of antineoplastic adjuvant therapies that
      use photodynamic generation of (1)O(2) to inactivate antioxidant defenses with a
      goal of sensitizing tumor cells to prooxidant-generating drugs.

PMID- 16910779
TI  - Glucose 6-phosphate dehydrogenase overexpression models glucose deprivation and
      sensitizes lymphoma cells to apoptosis.
AB  - Glucocorticoids are one component of combined treatment regimens for many types
      of lymphoma due to their ability to induce apoptosis in lymphoid cells. In
      WEHI7.2 murine thymic lymphoma cells, altering catalase and glutathione
      peroxidase activity by transfection or the use of chemical agents modulates the
      ability of glucocorticoids to induce apoptosis. This suggests that the oxidative
      stress response is important in determining the glucocorticoid sensitivity of the
      cells. For glutathione peroxidase and catalase to detoxify reactive oxygen
      species (ROS), reducing equivalents in the form of nicotinamide adenine
      dinucleotide phosphate, reduced form (NADPH) are ultimately required. The major
      source of NADPH in the cell is glucose 6-phosphate dehydrogenase (G6PDH).
      Therefore, we created G6PDH-overexpressing WEHI7.2 variants to test whether G6PDH
      activity is a key determinant of glucocorticoid sensitivity in WEHI7.2 cells.
      G6PDH-overexpressing WEHI7.2 cells were more sensitive to oxidative stress and
      glucocorticoids. The G6PDH-overexpressing WEHI7.2 variants appeared similar to
      cells undergoing glucose deprivation with decreased adenosine triphosphate (ATP)
      synthesis by the mitochondria and increased basal levels of ROS. Overexpression
      of G6PDH also sensitized the cells to other standard lymphoma chemotherapeutics
      including cyclophosphamide, doxorubicin, and vincristine. The decreased ATP and
      elevated ROS due to G6PDH overexpression may be key factors in increasing the
      sensitivity of the WEHI7.2 cells to lymphoma chemotherapeutics.

PMID- 16910780
TI  - The biphasic nature of nitric oxide responses in tumor biology.
AB  - The dual or biphasic responses of cancer to nitric oxide (NO) arise from its
      concentration dependent ability to regulate tumor growth, migration, invasion,
      survival, angiogenesis, and metastasis. The outcome of these various NO-dependent
      processes is dictated by several factors including NO flux, the chemical redox
      environment, and the duration of NO exposure. Further, it was recently discovered
      that an NO-induced redox flux in vascular endothelial cells hypersensitizes these
      cells to the antiangiogenic effects of thrombospondin-1. This suggests a novel
      treatment paradigm for targeting tumor-driven angiogenesis that combines redox
      modulation with mimetic derivatives of thrombospondin-1. This article discusses
      the biphasic nature of NO in cancer biology and the implications of NO-driven
      redox flux for modulation of tumor-stimulated angiogenesis, growth, and
      metastasis.

PMID- 16910781
TI  - ROS-production-mediated activation of AP-1 but not NFkappaB inhibits glutamate
      induced HT4 neuronal cell death.
AB  - Aside from their deleterious effect, reactive oxygen species (ROS) can function
      as small messenger molecules during physiologic processes. ROS have been shown to
      activate the transcription nuclear factor kappa B (NFkappaB) and activator
      protein 1 (AP-1). Exposure of HT4 neuronal cells to 10 mM glutamate results in
      cell death after 12 h. Here we show that glutamate treatment leads to an increase
      in ROS production and activation of AP-1, but not NFkappaB. 12-O
      Tetradecanoylphorbol 13-acetate (TPA), an activator of protein kinase C and an
      inducer of NFkappaB and AP-1, protected the cells. This protective effect was
      preceded by increased production of ROS compared with glutamate alone, which was
      accompanied by a synergistic increase in AP-1, but not NFkappaB activity. We used
      all-trans-retinoic acid (ATRA), overexpression of retinoic acid receptor alpha
      (RARalpha) and a decoy oligonucleotide inclusion assay to suppress AP-1 activity.
      NFkappaB was inhibited by using a super suppressor (IkappaBalphaDeltaN
      transfected cells). Inhibition of AP-1, but not NFkappaB resulted in increased
      cellular vulnerability to glutamate. Inhibition of AP-1 activity was coincident
      with a decrease in ROS production. Thus, although ROS are significant to the cell
      death effect induced by glutamate, they also activate protective pathways
      mediated by increasing AP-1 activity, and not that of NFkappaB.

PMID- 16910782
TI  - Role of oxidative/nitrosative stress in the tolerance to ischemia/reperfusion
      injury in cardiomyopathic hamster heart.
AB  - We investigated the role of oxidative/nitrosative stress in the tolerance to
      ischemia/reperfusion (I/R) injury in BIO14.6 cardiomyopathy hamster hearts at 6
      weeks of age. These hearts showed no significant morphologic change and left
      ventricular (LV) dysfunction. However, expression and activity of iNOS,
      nitrotyrosine (NT) formation, and protein kinase C (PKC)-epsilon activity were
      increased in these hearts. When the BIO14.6 hamster hearts were isolated and
      subjected to 40 min of global ischemia, they showed smaller myocardial necrosis
      and greater recovery of LV function during reperfusion compared with the control
      hamster heart. All of these effects were abrogated by prolonged treatment with
      the antioxidant, 2-mercaptopropionylglycine (MPG). Brief preischemic treatment
      with MPG or the iNOS inhibitor 1400W also abrogated NT formation and activation
      of PKC-epsilon and inhibited the tolerance to I/R injury in the BIO14.6 hamster
      heart. Brief preischemic treatment with the PKC inhibitor chelerythrine or the
      K(ATP) channel blockers, 5-hydroxydecanoate (5-HD) and glibenclamide, had no
      effect on iNOS activation and NT formation but inhibited the tolerance to I/R
      injury in the cardiomyopathic heart. These results suggest that
      oxidative/nitrosative stress plays a role in the tolerance to I/R injury in the
      cardiomyopathic heart through activation of PKC and the downstream effectors,
      K(ATP) channels.

PMID- 16910784
TI  - Novel aspects of oxidative stress-associated carcinogenesis.
AB  - Oxidative stress is associated with carcinogenesis. Reactive oxygen and nitrogen
      species contribute to the accumulation of mutations in the genome, presumably
      followed by selective processes. Recent data suggest that preferred signaling
      pathways exist for oxidative stress-associated carcinogenesis. Whether this
      completely depends on random mutations induced by reactive species or whether
      instead some fragile genomic loci are sensitive to oxidative damage in
      association with changes of transcriptional activity or other topologic or
      nontopologic effects remains to be explored. Reliable markers for oxidative
      stress as well as for oxidative stress-induced preneoplastic lesions must be
      established.

PMID- 16910783
TI  - The activation of metabolites of nitric oxide synthase by metals is both redox
      and oxygen dependent: a new feature of nitrogen oxide signaling.
AB  - Nitrite (NO(2)-), N (G)-hydroxy-L-arginine (NOHA), and hydroxylamine (NH(2)OH)
      are products of nitric oxide synthase (NOS) activity and can also be formed by
      secondary reactions of nitric oxide (NO). These compounds are commonly considered
      to be rather stable and as such to be dosimeters of NO biosynthesis. However,
      each can be converted via metal-catalyzed reactions into either NO or other
      reactive nitrogen oxide species (RNOS), such as nitrogen dioxide (NO(2)) and
      nitroxyl (HNO), which have biologic activities distinct from those of the parent
      molecules. Consequently, certain aspects of tissue regulation controlled by RNOS
      may be dictated to a significant extent by metal-dependent reactions, thereby
      offering unique advantages for cellular and tissue regulation. For instance,
      because many metal-catalyzed reactions depend on the redox and oxygen status of
      the cellular environment, such reactions could serve as redox indicators.
      Formation of RNOS by metal-mediated pathways would confine the chemistry of these
      species to specific cellular sites. Additionally, such mechanisms would be
      independent both of NO and NOS, thus increasing the lifetime of RNOS that react
      with NO. Thus metal-mediated conversion of nitrite, NOHA, and NH(2)OH into
      biologically active agents may provide a unique signaling mechanism. In this
      review, we discuss the biochemistry of such reactions in the context of their
      pharmacologic and biologic implications.

PMID- 16910785
TI  - Isoprostanes and related compounds: update 2006.
AB  - Last year Antioxidants and Redox Signaling devoted a special Forum issue (Volume
      7, 2005) to reviewing the current literature on isoprostanes (IsoPs) and related
      compounds. Awide variety of topics provided readers of that issue with important
      information on the chemistry and biology of these molecules. During the past
      year, more than 200 articles have been published in the field of IsoP research,
      and noteworthy advances in the area have been made. This editorial highlights
      selected aspects of these advances as they relate to the Forum issue. The main
      focus of this discussion is on the role of the IsoPs as biomarkers and mediators
      of oxidant stress in human disease, their mechanism of formation and metabolism,
      and their biologic activities.

PMID- 16910786
TI  - Joint International Conference on EPR Spectroscopy and wound healing.
AB  - The International Conference on Electron Paramagnetic Resonance Spectroscopy and
      Imaging of Biological Systems (EPR 2005) was held September 4 through 9, 2005, at
      Columbus, Ohio, U.S.A. Nearly 200 participants from 16 countries presented recent
      advances on the use of EPR technology to study biologic processes, with an
      emphasis on human health. For the first time, the EPR conference allied with the
      Wound Healing Conference, and the alliance opened an avenue for successful
      amalgamation of the basic biomedical and clinical aspects of wound healing with
      EPR technology and vice versa. This should lead to emerging applications of EPR
      technology in biomedical research and clinical practice.

PMID- 16910791
TI  - Outcomes from whose perspective?

PMID- 16910792
TI  - Easing the difficult journeys.

PMID- 16910793
TI  - Palliative care and physician responsibility.

PMID- 16910796
TI  - Palliative care has a role in the essential task of educating medical residents.

PMID- 16910797
TI  - Pediatric palliative care moving forward: empathy, competence, quality, and the
      need for systematic change.

PMID- 16910798
TI  - Mild, moderate, or severe pain categorized by patients with cancer with bone
      metastases.
AB  - PURPOSE: To examine how patients categorize their pain with the two commonly
      employed scales. METHODS AND MATERIALS: Patients with bone metastases referred to
      an outpatient palliative radiotherapy clinic were asked to rate their current
      pain on a numerical scale of 0-10 (0 = no pain, 10 = worst pain possible) and a
      categorized scale: none, mild, moderate and severe. RESULTS: Two hundred and
      seventeen patients were enrolled in the study. The median age was 66 years and
      median Karnofsky Performance Score was 70. The most common primary cancer sites
      were lung, prostate and breast. Based on patient-evaluated symptoms, 60% of
      patients who categorized pain as mild assigned it a 3 (24%) or 4 (36%), 63% who
      categorized pain as moderate assigned it a 5 (16.9%), 6 (19.1%) or 7 (27%) and
      80% who categorized pain as severe assigned it an 8 (28.2%), 9 (12.6%) or 10
      (39.8%). CONCLUSION: Our patients scored pain as mild if pain was < or =4,
      moderate if pain was 5-7 and severe if pain was > or =8.

PMID- 16910799
TI  - Cost and utilization outcomes of patients receiving hospital-based palliative
      care consultation.
AB  - OBJECTIVE: To compare per diem total direct, ancillary (laboratory and radiology)
      and pharmacy costs of palliative care (PC) compared to usual care (UC) patients
      during a terminal hospitalization; to examine the association between PC and ICU
      admission. DESIGN: Retrospective, observational cost analysis using a VA (payer)
      perspective. SETTING: Two urban VA medical centers. MEASUREMENTS: Demographic and
      health characteristics of 314 veterans admitted during two years were obtained
      from VA administrative data. Hospital costs came from the VA cost accounting
      system. ANALYSIS: Generalized linear models (GLM) were estimated for total
      direct, ancillary and pharmacy costs. Predictors included patient age, principal
      diagnosis, comorbidity, whether patient stay was medical or surgical, site and
      whether the patient was seen by the palliative care consultation team. A probit
      regression was used to analyze probability of ICU admission. Propensity score
      matching was used to improve balance in observed covariates. RESULTS: PC patients
      were 42 percentage points (95% CI, -56% [corrected] to -31%) less likely to be
      admitted to ICU. Total direct costs per day were $239 (95% CI, -387 to -122)
      lower and ancillary costs were $98 (95% CI, -133 to -57) lower than costs for UC
      patients. There was no difference in pharmacy costs. The results were similar
      using propensity score matching. CONCLUSION: PC was associated with significantly
      lower likelihood of ICU use and lower inpatient costs compared to UC. Our
      findings coupled with those indicating better patient and family outcomes with PC
      suggest both a cost and quality incentive for hospitals to develop PC programs.

PMID- 16910800
TI  - How do we interpret the answer "Neither" when physicians ask patients with cancer
      "Are you depressed or not?".
AB  - OBJECTIVES: The aim of this study was to clarify how physicians should interpret
      the answer "neither" to the single-question interview, "Are you depressed or
      not?" PATIENTS AND METHODS: Two hundred fifty-one patients with cancer were
      studied. The patients were directly interviewed, choosing one answer among these
      three: "Yes, I am depressed"; "No, I am not depressed"; or "Neither." After this,
      the patients completed the Hospital Anxiety and Depression Scale (HADS). The
      threshold of 11 or greater on HADS was used for adjustment disorder and major
      depressive disorder. RESULTS: All patients could reply to the single question,
      but 10 patients did not complete HADS. Among 83, 81 and 77 patients who answered
      "yes," "neither," and "no," respectively, 75 (90%), 43 (65%), and 9 (12%)
      patients scored 11 or more on HADS. The mean score of HADS was 12.2 in patients
      who answered "neither," significantly higher than that of the "no" group (p <
      0.0001) and significantly lower than that of the "yes" group (p < 0.0001).
      CONCLUSION: Patients who answered "neither" frequently scored in a high enough
      range to warrant further investigation for adjustment or depressive disorder.

PMID- 16910801
TI  - Redefining cancer-related asthenia-fatigue syndrome.
AB  - BACKGROUND: Asthenia fatigue syndrome (AFS) is a common symptom perceived by
      patients with cancer and consists of reported pathologic fatigue, poor endurance,
      and impaired motor and cognitive function. OBJECTIVE: The purpose of this study
      was to examine the relationship between a traditional measure of AFS, visual
      analogue scale (VAS) fatigue ratings, and a set of more objective functional and
      physiologic measures (Dietz oncology classification, C-reactive protein, serum
      albumin, hemoglobin, body mass index [BMI]), Motor Functional Independence
      Measure (FIM) Score, Cognitive FIM Score. We hypothesized a relationship could
      suggest the utility of alternative means of assessing and addressing AFS.
      METHODS: We retrospectively examined the records of 131 patients admitted to our
      facility for inpatient rehabilitation because of disability-causing cancer or its
      treatment. RESULTS: Of our sample, 94.7% (124 cases) indicated at least mild
      fatigue and 97.7% (128 cases) showed abnormal serum albumin, C-reactive protein,
      hemoglobin, or BMI. We used multiple regression analysis to examine the
      relationship between VAS fatigue ratings and the aforementioned set of functional
      and physiologic variables. The regression explained a significant proportion of
      the variability in VAS fatigue ratings (F = 2.25, df = 7,123, p = 0.03, R = 0.34,
      R(2) = 0.11). However, only Motor FIM Score accounted for a significant
      independent contribution to the variability in VAS fatigue ratings. CONCLUSION:
      The data indicate physiologic and functional variables may provide an
      alternative, objective, and reliable operational definition of AFS. Specifically,
      using Motor FIM Score, as a surrogate for VAS fatigue ratings may be used to
      measure the efficacy of AFS treatment.

PMID- 16910802
TI  - Unrestricted opiate administration for pain and suffering at the end of life:
      knowledge and attitudes as barriers to care.
AB  - BACKGROUND: Pain and symptom management is critical for quality end-of-life care
      in the hospital. Although guidelines support the use of unrestricted opiate
      administration to treat refractory pain and suffering in the dying patient, many
      patients die suffering with symptoms that could have been addressed. METHODS: A
      multidisciplinary convenience sample of 381 hospital-based health care providers
      completed a survey evaluating their understanding of the principles of treating
      refractory pain and suffering at the end of life in the hospital, knowledge of
      the institution's policy about how to implement such care, and attitudes about
      and comfort with such treatment. RESULTS: Respondents recognized pain and symptom
      management as a goal of unrestricted opiate use at the end of life, but 12%
      identified comfort for families or treatment of nonphysical suffering as the
      principal goal of this modality. Two thirds of respondents felt that unrestricted
      opiates were used too rarely and 45% felt they were used too late. However, 16%
      felt uncomfortable administering unrestricted opiates and 21% of physicians and
      nurses who had used restricted opiates reported having felt pressured to increase
      dosing of opiates. Knowledge deficits concerning appropriate candidates for
      unrestricted opiates and the protocol for appropriate implementation were common.
      CONCLUSIONS: Knowledge deficits and attitudinal concerns may hamper the
      administration of unrestricted opiates for refractory pain and suffering at the
      end of life in the hospital. Clinician education and clarification of the
      appropriate use of this modality when there are differences in clinician and
      family perception of discomfort are needed.

PMID- 16910803
TI  - Prescription drug spending for Medicare+Choice beneficiaries in the last year of
      life.
AB  - BACKGROUND: In 2006, Medicare implemented its prescription benefit plan.
      Therefore, insights into medication costs at the end of life may help guide
      clinicians to navigate Medicare Part D coverage for chronically ill individuals.
      OBJECTIVES: We examined drug spending by disease and demographics for
      Medicare+Choice (M+C) beneficiaries in the last year of life (LYOL). RESEARCH
      DESIGN: Retrospective review of M+C decedents' drug claims and enrollment data
      collected between January 1998 and December 2000, supplemented by the Medicare
      denominator file and 1990 Census data. SUBJECTS: Four thousand six hundred two
      beneficiaries in a large national managed care organization. MEASURES: We
      analyzed the relationship between prescription drug expenditures and
      sociodemographic descriptors, insurance characteristics, and cause of death.
      RESULTS: The mean annual number of prescriptions filled was 36.9; the managed
      care organization (MCO) paid $539 and beneficiaries paid $627. Higher
      expenditures were significantly correlated with female gender, higher number of
      comorbidities, and whether beneficiaries obtained the insurance as an employer
      based retiree benefit. Minority beneficiaries had 26% fewer prescriptions.
      Increasing levels of annual median household income corresponded with a 20%
      increase in the number of prescriptions and a 25% increase in mean out-of-pocket
      expenses, between those with a median household income of less than $20,000 and
      those with $40,000 or greater. In the LYOL, chronic obstructive pulmonary disease
      and diabetes had the highest average number of prescriptions and total
      expenditures. Individuals dying from strokes or other unclassifiable conditions
      had the lowest average number of prescriptions and average total expenditures.
      CONCLUSION: Medication expenditures in the LYOL were highly dependent upon
      selected sociodemographic, insurance characteristics, and disease states.

PMID- 16910804
TI  - Impact of a palliative care service on in-hospital mortality in a comprehensive
      cancer center.
AB  - BACKGROUND: Palliative care services provide symptom control and psychosocial
      support for dying patients and their families. These services are not available
      in many cancer centers and tertiary hospitals. The purpose of this study was to
      review the impact of a palliative care program, established in 1999, on overall
      in-hospital mortality. METHODS: We reviewed the M. D. Anderson Cancer Center
      computerized database to determine the total number of deaths and discharges and
      the place of death for each fiscal year from 1999 to 2004. The median length of
      stay for patients who died in different locations within the hospital was
      calculated. Annual palliative care consultations for patients who subsequently
      died in the hospital were retrieved. The annual mortality rate for the cancer
      center was calculated. RESULTS: The overall in-hospital mortality rates were 3.6,
      3.7, 3.6, 3.5, 3.6, and 3.7% of all discharges for the period 1999-2004
      respectively (p > 0.2). The number of deaths in the medical intensive care unit
      (MICU) dropped from 252 in 671 (38%) in 1999 to 213 in 764 (28%) in 2004 (p <
      0.0001). Involvement of the palliative care service in the care of patients dying
      in the hospital grew from 8 in 583 (1%) in 1999 to 264 in 764 (35%) in 2004 (p <
      0.0001). The median length of hospital stay (MLOS) for patients who subsequently
      died in-hospital was significantly longer than that for patients who were
      discharged alive. CONCLUSIONS: Increased involvement by the palliative care
      service in the care of decedent patients was associated with a decreased MICU
      mortality and no change in overall hospital mortality rate or inpatient length of
      hospital stay.

PMID- 16910805
TI  - Survival, mortality, and location of death for patients seen by a hospital-based
      palliative care team.
AB  - BACKGROUND: Little is known about patient outcomes after discharge planning by
      inpatient palliative care teams. A major difficulty is that successful discharge
      planning often effectively limits or ends the team's relationship with the
      patient and family. The goal of this study was to gather a clearer picture of
      what happened to our palliative care consult patients after discharge. METHODS:
      This was a longitudinal survey of all patients seen over a one year period by the
      inpatient palliative care team at Oregon Health & Science University (OHSU). Data
      were recorded by team members at the time of consultation and supplemented by
      data from administrative databases and death certificates. RESULTS: The team
      provided consults to 292 unique patients: 60% were younger than age 65, 39% were
      female, and 16% were members of an ethnic or racial minority. Almost three
      quarters of patients carried a non-cancer diagnosis. Of the 292 patients, 37%
      died in hospital and 63% were discharged alive, either to home (54%), nursing
      facilities (20%), or inpatient hospice (26%). Of the 183 patients discharged
      alive, 38% died within 2 weeks, 32% died between 2 weeks and 6 months, 25% were
      alive at 6 months, and 4% were unknown. Of note, only 10% of patients seen by the
      consult service were readmitted to OSHU within 30 days, and only 5% of those
      discharged alive from OHSU ultimately died in an acute care hospital. DISCUSSION:
      We characterized patient outcomes following inpatient palliative care
      consultation: where patients are discharged, how long they live, and where they
      die. Two thirds of patients were able to be discharged, even when death occurred
      within two weeks. The low rates of readmission and death in an acute care
      hospital support that the decision to discharge the patients was reasonable and
      the discharge plan was adequate. Hospital based palliative care teams can play an
      important and unique role in discharge planning--allowing even patients very near
      death to leave the hospital if they wish.

PMID- 16910807
TI  - Interdisciplinary interventions to improve pediatric palliative care and reduce
      health care professional suffering.
AB  - OBJECTIVE: To implement and evaluate a quality improvement program of
      interdisciplinary palliative care education and support intended to increase the
      competence, confidence and ability to manage personal grief of health care
      professionals caring for dying children. SETTING: A children's hospital in an
      urban academic medical center. PARTICIPANTS: Pediatric health care professionals
      of all disciplines caring for children with life-threatening conditions.
      INTERVENTIONS: We initiated a quality improvement program of professional
      education and support consisting of four interdisciplinary activities facilitated
      by the pediatric palliative care team. The Compassionate Care Network (CCN)
      provides an open forum for interdisciplinary networking and education. Palliative
      Care Rounds (PCR) provides education through monthly case-based discussions on
      selected units. Patient Care Conferences (PCC) facilitate communication and care
      planning for selected patients with palliative care needs on any unit in the
      children's center. Bereavement Debriefing Sessions (BDS) offer health
      professionals the opportunity to manage their responses to grief after a
      patient's death. EVALUATION MEASURES: From February 2002 to September 2003, we
      prospectively tracked the frequency of sessions conducted, the number and
      discipline of attendees, the age and diagnosis of patients discussed, and themes
      raised at each session. Participants evaluated each session. RESULTS: One hundred
      one sessions were conducted (PCR = 31, PCC = 23, CCN = 9, BDS = 38) for 950
      participants (PCR = 312, PCC = 188, CCN = 193, BDS = 257). All units and
      disciplines participated in one or more sessions. Evaluations report that
      sessions are informative and will influence future professional practice.
      CONCLUSIONS: A program of interdisciplinary interventions can successfully
      educate and support health care professionals in providing palliative and end-of
      life care for children. This program model can be applied in diverse pediatric
      health care settings.

PMID- 16910806
TI  - Caring for a loved one with advanced cancer: determinants of psychological
      distress in family caregivers.
AB  - BACKGROUND: Family caregivers caring for a patient with terminal cancer may
      experience significant psychological distress. OBJECTIVE: The purpose of this
      study was to determine the extent to which the family caregivers' psychological
      distress is influenced by the patients' performance status while taking into
      account individual characteristics of caregivers and their unmet needs. METHODS:
      Two hundred twelve family caregivers were assigned to three cohorts according to
      the patient's performance status, as measured by the Eastern Collaborative
      Oncology Group Functional Scale (ECOGS). Interview information was collected on
      the services and care provided, as well as on the caregivers' characteristics and
      level of psychological distress. RESULTS: Family caregivers' psychosocial
      distress is strongly associated with the patients' terminal disease progress and
      declined functioning. The level of psychological distress varies from 25.2 to
      33.5 (p = 0.0008) between the groups. Moreover, the percentage of caregivers with
      a high level of psychological distress varies from 41% to 62%, while this
      percentage is estimated at 19.2% in general population. A high distress index was
      significantly associated with the caregiver's burden, the patient's young age,
      the patient's symptoms, the caregiver's young age and gender, a poor perception
      of his/her health and dissatisfaction with emotional and tangible support.
      CONCLUSIONS: Family caregivers of patients in the advanced stages of cancer
      experience a high level of psychological distress, which increases significantly
      as the patient loses autonomy. Health care policies and programs need to be
      revisited in order to take the reality of these patients and their families into
      account.

PMID- 16910808
TI  - Peer-professional workgroups in palliative care: a strategy for advancing
      professional discourse and practice.
AB  - BACKGROUND: As part of a comprehensive national effort to improve care at the end
      of life, the Promoting Excellence in End-of-Life Care program of The Robert Wood
      Johnson Foundation convened "national peer-professional workgroups" of recognized
      authorities or leaders to advance palliative aspects of practice in their
      respective specialties or fields. OBJECTIVE: The conveners' goals were to
      establish research and practice agendas to integrate palliative care within
      selected fields and health care settings, and to expand delivery of palliative
      care to special patient populations that have been underserved by palliative
      care. We hypothesized that leading professionals within specific fields,
      chartered to achieve clear goals, and then provided with sufficient
      administrative and logistical support, could develop recommendations for
      expanding access to, quality of and financing for palliative care within their
      disciplines. DESIGN: Staff at the national program office of Promoting Excellence
      in End-of-Life Care convened eight disease-based, specialty-based or issue-based
      workgroups (the selected workgroup topics were amyotrophic lateral sclerosis,
      cost accounting, critical care, end-stage renal disease, human immunodeficiency
      virus/acquired immune deficiency syndrome [HIV/AIDS] disease, Huntington's
      disease, pediatric care, and surgical palliative care). The national program
      office implemented a small group process design in convening the groups, and
      provided coordination, oversight and administrative support, along with funds to
      support meetings (telephone and in-person). A workgroup "charter" guided groups
      in determining the scope of efforts and set specific, time-limited goals. From
      the outset, the workgroups developed plans for dissemination of workgroup
      recommendations to defined stakeholder audiences, including health care
      providers, policy-makers, payers, researchers, funders, educators, professional
      organizations and patient advocacy groups. SETTING AND SUBJECTS: Groups averaged
      25 members and met for an average of 24 months. Promoting Excellence leadership
      chose workgroup topic areas that addressed patient populations underserved for
      palliative care, and corresponding professional specialties with demonstrated
      interest and readiness to improve education, evidence base, and professional
      expertise in palliative aspects of care. RESULTS: Each workgroup was highly
      productive and advanced changes in respective fields through developing and
      disseminating recommendations to their respective fields regarding practice,
      education, clinical and health service research and policy. Beyond their
      chartered responsibilities, workgroups also developed educational programs and
      curricula and a wide array of resources. The workgroups also authored articles
      for publication, intended to stimulate professional discourse and influence
      clinical norms and culture. CONCLUSIONS: The national peer-professional workgroup
      model exceeded original expectations and produced well-considered Recommendations
      to the Field as well as a body of resources for professionals in expanding access
      to and quality of palliative care. Results of this experimental venture in
      professional change suggest that the workgroup model may be a useful, cost
      effective, rapid-change strategy for quality improvement in other areas of
      professional practice and service delivery.

PMID- 16910809
TI  - Quality of life of patients with advanced cancer and acquired immune deficiency
      syndrome and their family caregivers.
AB  - BACKGROUND: Although definitions of palliative care include quality of life as a
      central concern, little research has been published about both the quality of
      life of patients with advanced illness and their family members, and particularly
      the changes in their quality of life over time. OBJECTIVES: The aims of this
      prospective longitudinal pilot study were to: (1) establish the reliability of
      multidimensional quality of life instruments based on patients with acquired
      immune deficiency syndrome (AIDS) and patients with cancer and caregivers; (2)
      identify differences in quality of life between patients with advanced AIDS and
      cancer, and their family caregivers with consideration of mortality, attrition,
      and compliance rates; and (3) examine differences in demographic variables and
      their potential confounding effect when measuring quality of life. METHODS: The
      sample included 101 patients with advanced illness (63 patients with advanced
      AIDS and 38 with advanced cancer) and 81 family caregivers (43 caregivers for
      patients with AIDS and 38 caregivers for patients with cancer). Data collection
      involved the monthly completion of the McGill Quality of Life Questionnaire
      (MQOL) for patients, and the Quality of Life Scale (QLS) for family caregivers.
      RESULTS: Reliability of the MQOL and QLS were established for patients with AIDS
      and patients with cancer and caregivers. Based on the MQOL, patients with
      advanced AIDS reported a lower total quality of life, and lower psychological
      quality of life, and a higher physical quality of life compared to patients with
      advanced cancer. There were no significant differences between patient groups on
      the one-item physical well-being subscale, or the existential well-being, and
      support subscales. Based on the QLS, AIDS caregivers reported greater overall
      quality of life, greater psychological well-being, and greater spiritual well-be-
      ing than cancer caregivers. There were no significant differences between AIDS
      and cancer caregivers with respect to physical or social well-being. From
      baseline entry into the study to third month of participation, there were no
      significant changes in total quality of life scores for patient or caregiver
      groups, although trends indicated a moderately high total quality of life over
      time for all patient and caregiver groups. Fourteen of 63 (22%) patients with
      AIDS patients died, while 19 of 38 (50%) patients with advanced cancer died after
      enrollment. Forty-six of 63 (73%) patients with advanced AIDS withdrew for
      various reasons other than death at some point during the 12 month time frame of
      the study, while 15 of 38 (39%) patients with advanced cancer withdrew. There
      were significant differences on all demographic variables for patients with
      advanced cancer and AIDS. Only religious affiliation was significantly related to
      quality of life for patients with AIDS, while gender was the only variable
      associated with quality of life for patients with cancer. There were significant
      differences on all demographic variables between caregivers with the exception of
      gender and living arrangements. Only the relationship between patients and
      caregivers and marital status were significantly associated with quality of life
      for cancer caregivers. CONCLUSIONS: In palliative care research, the challenge is
      to design studies that will capture changes in the domains of quality of life
      over time, yet will minimize participant burden and subsequent attrition rates.
      By measuring quality of life as an outcome variable in palliative care, health
      professionals can identify changes in the domains of quality of life over time
      for various patient populations and their family caregivers, and respond with
      appropriate interventions, which promote or maintain their quality of life even
      as death approaches.

PMID- 16910810
TI  - Evaluation of an educational intervention to encourage advance directive
      discussions between medicine residents and patients.
AB  - INTRODUCTION: Most medical schools are remiss in preparing physicians in end-of
      life communication skills. As a result, many residents are uncomfortable with
      approaching the patient, have not developed the skills required to discuss the
      patients' wishes, and avoid end-of-life conversations. OBJECTIVE: To evaluate an
      educational intervention focused on teaching residents skills to discuss advance
      directives. METHODS: Medicine Residents attended a morning report consisting of
      both didactic training and participation in a role-play exercise. Charts of
      inpatients were audited ten days prior to and five days subsequent to the
      intervention to ascertain if there was a documented do-not-resuscitate (DNR)
      discussion. RESULTS: Seventy-nine records of patients assigned to eight
      physicians who attended the intervention and who were responsible for patients
      before and after the intervention were reviewed. Of the patients assigned to
      these residents before the intervention, 32% had a documented DNR discussion.
      Thirty-four (34%) of the physicians had discussions after the intervention,
      demonstrating only minimal improvement. CONCLUSIONS: A single intervention may be
      inadequate to affect physician practices related to DNR discussions. Physicians
      may need more interactive, experiential learning opportunities and related
      supervision over the course of their training in order to improve these
      communication skills. A chart review that only records if a DNR discussion was
      documented in the medical record may not be the best tool to evaluate the success
      of this educational intervention. Improvement in attitudes and knowledge were not
      able to be measured.

PMID- 16910811
TI  - Interest in research participation among hospice patients, caregivers, and
      ambulatory senior citizens: practical barriers or ethical constraints?
AB  - OBJECTIVES: The purpose of this survey study was to explore hypothetical interest
      in research participation among hospice patients and caregivers compared to
      ambulatory senior citizens. DESIGN: Cross-sectional survey. SETTING: Twenty-one
      community-based hospice offices, a university medical center geriatric ambulatory
      care clinic, and 3 community-based senior citizen centers. PARTICIPANTS:
      Participants were hospice patients, caregivers, and ambulatory senior citizens
      not enrolled in hospice. MEASUREMENTS: Using a self-administered questionnaire,
      participants rated their interest in participating in survey/interview and
      therapeutic studies, identified potential benefits and barriers to research
      participation, and reported their preferences for who they would want to approach
      them about research participation. RESULTS: Forty-six percent of hospice patients
      and 60% of caregivers reported an interest in interview or survey research
      participation; 45% and 57%, respectively, expressed interest in therapeutic
      research. Compared to hospice patients, caregivers reported higher rates of
      personal interest in both survey research (p =< 0.001) and therapeutic research
      (p=<0.001) and were more likely to report that the hospice patients they cared
      for would be interested (p = 0.005 and p = 0.027). Younger hospice patients were
      more favorably disposed toward both survey and therapeutic research participation
      than hospice patients over the age of 75 (p = 0.063 and 0.011). The proportion of
      older hospice patients showing interest in research did not differ significantly
      from ambulatory senior citizens for either type of research (p = 0.56, 0.98).
      CONCLUSION: This study suggests that many hospice patients are interested in
      research participation and are able to articulate benefits and barriers, which
      supports the inclusion of this population in research.

PMID- 16910812
TI  - Editorial: renal palliative care: supporting our colleagues, patients, and
      family.

PMID- 16910813
TI  - Renal palliative care.
AB  - Patients with chronic kidney disease have a shortened life expectancy and carry a
      high symptom burden. Clinicians need sophisticated expertise in pain and symptom
      management and skills in communication to meet the many needs of this population.
      This article reviews the literature and discusses prognosis, ethical and legal
      considerations, symptoms, treatment, and end-of-life issues. The field of
      nephrology is shifting from an exclusive focus on increasing survival to one that
      provides greater attention to quality of life. There is an opportunity to
      integrate many of the advances of palliative medicine into the comprehensive
      treatment of these patients.

PMID- 16910814
TI  - The palliative Prognostic Score #62.

PMID- 16910815
TI  - The Palliative Performance Scale #125.

PMID- 16910816
TI  - A day in the life of a hospice physician.

PMID- 16910817
TI  - You have to know how to shudder.

PMID- 16910818
TI  - Palliative care case report: leptomeningeal carcinomatosis.

PMID- 16910823
TI  - JPM Patient Information. Oxygen therapy at the end of life.

PMID- 16910825
TI  - Molecular epidemiology of HIV Type 1 in Ukraine: birthplace of an epidemic.
AB  - During the 1990s, HIV-1 spread rapidly through drug networks in Ukraine and from
      there throughout the former Soviet Union. To examine the origins of this
      epidemic, the genetics of HIV-1 in Ukraine were studied. Proviral DNA from PBMC
      was extracted and PCR amplified. Part of pol and nearly full genomes of HIV-1
      were sequenced and characterized. The predominant genetic form in 163 strains was
      subtype A (66%), followed by subtypes B (30%), C (2%), D (1%), and a new AB
      recombinant form (1%). HIV strains from Kiev were diverse having subtypes A, B,
      C, and D. In Crimea, Donetsk, Poltava, and Odessa, however, the strains were
      overwhelmingly subtype A, while in Nikolaev subtype B predominated. After the
      near simultaneous introduction of subtypes A and B in Ukraine, subtype B remained
      where it was introduced while subtype A spread widely, creating the fastest
      growing epidemic in the world.

PMID- 16910826
TI  - Delay in the initiation of HAART, poorer virological response, and higher
      mortality among HIV-infected injecting drug users in Spain.
AB  - Differences in the uptake and time to initiation of highly active antiretroviral
      therapy (HAART), the virological response to HAART, and survival from AIDS by
      transmission category were analyzed. A multicenter hospital-based cohort of HIV
      infected patients attending 10 hospitals in Spain from January 1997 to December
      2003 was used. Cross-checks with the National AIDS Registry were performed. Cox
      proportional hazard models were used to assess the impact of transmission
      category on time to HAART initiation, viral suppression (defined by first HIV-1
      RNA viral load measurement <500 copies/ml after HAART), and survival from AIDS.
      Of 4643 patients, 73% were men and 56% were injecting drug users (IDUs). A
      statistically significant interaction was found between transmission category and
      previous non-HAART antiretroviral treatment (ART) (p < 0.05). Among ART naive
      patients, IDUs had a 33% lower risk of initiating HAART compared to men who have
      sex with men (MSM) [HR 0.67 (95% CI 0.57-0.79)]. No differences by transmission
      categories were seen among patients with prior non-HAART ART. IDUs had poorer
      viral load (VL) suppression than MSM [HR 0.86 (95% CI 0.74-0.99)] adjusting by
      baseline VL, AIDS diagnosis, and prior ART. Mortality from AIDS was two and a
      half times higher in IDUs than MSM [HR 2.51 (95% CI 1.03-6.1)]. Among patients
      who access the hospital network, IDUs have a lower uptake of HAART, have worse
      virological suppression, and have higher mortality after AIDS diagnosis. There is
      a need to extend the programs in order to enhance access and adherence of IDUs to
      HAART and consider the treatment of drug addiction as an integral part of the
      treatment for HIV infection.

PMID- 16910828
TI  - Immunological and virological effects of structured treatment interruptions
      following exposure to hydroxyurea plus didanosine.
AB  - Both hydroxyurea (HU) and structured treatment interruptions (STI) have been
      investigated as therapeutic approaches to enhance immune responses in chronically
      HIV-infected individuals. HIV-specific T cell responses as well as T cell
      activation were analyzed longitudinally in 31 HIV-infected individuals who had
      been treated for the prior 12 months with didanosine (ddI) plus HU and thereafter
      completed three STI cycles consisting of 2 months off and 2 months on ddI-HU.
      Similar increases in plasma HIV-RNA were seen in each of the three cycles off
      therapy, whereas CD4 counts remained fairly stable along the study period. T cell
      activation paralleled the evolution of plasma HIV-RNA during the first STI cycle
      and waned afterward. At baseline most patients presented a high level of CD8+
      responses to different HIV peptide pools and 23% of them had CD4+ responses to
      Gag and/or Env. The level of CD8+ responses against each pool was stable and did
      not increase during STI cycles, while CD4 responses tended to decline. However,
      the contribution of Nef-specific response to the total CD8 response tended to
      increase. In a multivariate model, both a higher baseline plasma HIV-RNA and a
      higher level of Nef-specific response contribution to the total CD8+ response
      were independently associated with lower plasma HIV-RNA increases during each of
      the three STI cycles. Nef-specific CD8+ responses might contribute to a better
      virological control of HIV replication following treatment interruptions in HIV
      infected individuals and might be boosted by the immunomodulatory effect of HU.

PMID- 16910829
TI  - Urinary beta2-microglobulin as a possible sensitive marker for renal injury
      caused by tenofovir disoproxil fumarate.
AB  - Tenofovir disoproxil fumarate (TDF) is renally excreted by a combination of
      glomerular filtration and active tubular secretion, and its renal safety profiles
      have been reported based on a limited increase of serum creatinine (sCr) levels.
      However, renal tubular function has not previously been well monitored. We
      measured sCr and urinary beta2-microglobulin (U-beta2MG) levels cross-sectionally
      in 70 patients treated with TDF [TDF+] and 90 patients on other antiretroviral
      therapy who had never been exposed to TDF [TDF-]. The mean U-beta2MG was
      significantly higher in TDF+ patients than that in TDF- patients (p < 0.0001),
      though no statistical difference was detected in their creatinine clearance
      estimated by using the Cockcroft-Gault equation. Multivariate analysis showed
      that coadministration of boosted lopinavir (LPV) and patients' body weight were
      associated with U-beta 2MG levels in TDF+ patients. U-beta2MG levels were
      significantly higher in those who also received boosted LPV [TDF+LPV+] (p =
      0.0007), and abnormally high levels were noted in 67.7% of them. Furthermore, in
      the TDF+LPV+ group, U-beta2MG levels showed significant negative correlation with
      patients' body weight (p = 0.0029) and abnormal U-beta2MG was observed in all six
      patients with body weight less than 55 kg. In four patients, a rapid fall in U
      beta2MG occurred after cessation of TDF. Relative to sCr, U-beta2MG could be a
      more sensitive marker of renal tubular injury caused by TDF. Boosted LPV co
      administration and low body weight may be risk factors for TDF-induced renal
      tubular dysfunction, probably because these factors are associated with an
      increase in TDF concentration.

PMID- 16910827
TI  - HIV Type 1 molecular epidemiology in cuba: high genetic diversity, frequent
      mosaicism, and recent expansion of BG intersubtype recombinant forms.
AB  - Highly diverse HIV-1 genetic forms are circulating in Cuba, including subtypes B
      and G and two recombinant forms of African origin (CRF18_cpx and CRF19_cpx). Here
      we phylogenetically analyze pol sequences from a large collection of recent
      samples from Cuba, corresponding to 425 individuals from all Cuban provinces,
      which represents approximately 12% of prevalent infections in the country. RNA
      from plasma was used to amplify a pol segment by reverse transcription-polymerase
      chain reaction; phylogenetic analyses were performed with neighbour-joining trees
      and bootscanning. The distribution of genetic forms was subtype B, 41.2%;
      CRF19_cpx, 18.4%; BG recombinants, 11.6%; CRF18_cpx, 7.1%; subtype C, 6.1%;
      subtype G, 3.8%; B/CRF18 recombinants, 2.6%; subtype H, 2.1%; B/CRF19
      recombinants, 1.7%; and others, 5.4%. Seventy-five (17.6%) viruses were
      recombinant between genetic forms circulating in Cuba. In logistic regression
      analyses, adjusting by gender and region, subtype B was more prevalent (OR 5.0,
      95% CI 2.0-12.3) and subtype G less prevalent (OR 0.1, 95% CI 0.0-0.5) among men
      who have sex with men (MSM) than among heterosexuals. Within the main genetic
      forms of Cuba there were phylogenetic subclusters, several of which correlated
      with risk exposure or region. BG recombinants formed three phylogenetically
      related subclusters, corresponding to three different mosaic structures; most of
      these recombinants were from MSM from Havana City, among whom they have expanded
      recently, reaching 31% HIV-1 infections diagnosed in 2003. This study confirms
      the high HIV-1 diversity and frequent recombination in Cuba and reveals the
      recent expansion of diverse related BG recombinant forms in this country.

PMID- 16910830
TI  - Pharmacokinetics of saquinavir hard-gel/ritonavir and atazanavir when combined
      once daily in HIV Type 1-infected individuals administered different atazanavir
      doses.
AB  - The pharmacokinetics and short-term safety of atazanavir 150 and 200 mg, when
      coadministered with saquinavir/ritonavir 1600/100 mg once daily, were evaluated.
      On day 1, atazanavir 150 mg once daily, was added to saquinavir/ritonavir
      regimens and sampling was performed to evaluate saquinavir, ritonavir, and
      atazanavir pharmacokinetics (day 11). Atazanavir was increased to 200 mg and
      pharmacokinetic assessment repeated (day 30). Geometric mean ratios (GMR) and 95%
      confidence intervals (CI) were used to compare saquinavir, ritonavir, and
      atazanavir pharmacokinetic parameters in the present study and for 14 of the
      subjects treated with saquinavir/ritonavir 1600/100 mg once daily without and
      with atazanavir 300 mg who participated in a previous trial. Geometric mean (GM)
      saquinavir AUC0-24, Ctrough, and Cmax were 30,589 and 32,312 ng . h/ml, 166 and
      182 ng/ml, and 4267 and 4261 ng/ml when coadministered with atazanavir 150 and
      200 mg (n = 18). On days 11 and 30, saquinavir and atazanavir Ctrough remained
      >100 ng/ml in 13/18, 14/18, 18/18, and 17/18 patients. Among the above mentioned
      14 subjects, significant increases in saquinavir Ctrough (87%, 92%, 99%), Cmax
      (40%, 55%, 44%), and AUC0-24 (51%, 60%, 63%) were observed with atazanavir 300,
      150, and 200 mg. Ritonavir AUC0-24 and Cmax were significantly increased with the
      addition of atazanavir 300 mg only. Atazanavir enhances saquinavir and ritonavir
      by a mechanism that requires elucidation. While saquinavir enhancement was
      apparently independent of atazanavir dose, atazanavir 300 mg produced an increase
      in ritonavir Cmax, which is not observed with lower atazanavir doses. Atazanavir
      related hyperbilirubinemia was dose dependent. However, higher saquinavir and
      atazanavir exposure may be required to suppress HIV-resistant strain replication.

PMID- 16910831
TI  - Elevations in IL-10, TNF-alpha, and IFN-gamma from the earliest point of HIV Type
      1 infection.
AB  - Perturbations of plasma IL-10, IL-12, IL-13, TNF-alpha, and IFN-gamma were
      measured longitudinally in HIV-1 seroconverting plasma donors and were compared
      to subjects with symptomatic primary HIV-1 infection. Control groups included
      uninfected patients with symptoms and risks for primary HIV-1, healthy controls,
      and asymptomatic plasma donors with primary HCV. IL-10, TNF-alpha, and IFN-gamma
      rapidly rose in acute HIV-1 infection, while IL-13 predominated in acute HCV.
      Subjects with symptomatic primary HIV-1 had higher cytokine levels than
      asymptomatic subjects, statistically significant for TNF-alpha. Cytokine
      alterations occurred within 7 days of detectable HIV-1 viremia, emphasizing the
      need to study the earliest events of infection.

PMID- 16910832
TI  - Interaction of macrophages with apoptotic cells enhances HIV Type 1 replication
      through PGE2, PAF, and vitronectin receptor.
AB  - Phagocytosis of apoptotic cells by macrophages increases secretion of soluble
      mediators and generates an antiinflammatory environment. We previously reported
      that phagocytosis of apoptotic cells by HIV-1-infected macrophages enhances viral
      replication, with the participation of the cytokine transforming growth factor-
      beta1 and an integrin receptor. Now, we describe the role of prostaglandin E2
      (PGE2), platelet-activating factor (PAF), and the integrin alphaVbeta3
      (vitronectin receptor, VnR) in this phenomenon. Exacerbation of HIV-1 growth
      induced by phagocytosis of apoptotic cells was inhibited when HIV-1-infected
      macrophages were treated with a cyclooxygenase 2 inhibitor, or with a PAF
      receptor antagonist (BN 52021) immediately after macrophage interaction with
      apoptotic cells. Treatment of HIV-1-infected macrophages with BN 52021 decreased
      viral replication, whereas addition of PGE2 or PAF to these cells enhanced viral
      replication. Monoclonal antibodies (MAbs) to VnR reduced the macrophage uptake of
      apoptotic cells, prevented the enhancement of HIV-1 growth upon the engulfment of
      apoptotic cells, and potently augmented viral replication in HIV-1-infected
      macrophages in the absence of apoptotic cells. In conclusion, PGE2 and PAF, and
      ligation of VnR as well, contribute to amplify viral growth in HIV-1-infected
      macrophages upon uptake of apoptotic cells.

PMID- 16910833
TI  - Subtype-specific patterns in HIV Type 1 reverse transcriptase and protease in Oyo
      State, Nigeria: implications for drug resistance and host response.
AB  - As the use of antiretroviral therapy becomes more widespread across Africa, it is
      imperative to characterize baseline molecular variability and subtype-specific
      peculiarities of drug targets in non-subtype B HIV-1 infection. We sequenced and
      analyzed 35 reverse transcriptase (RT) and 43 protease (PR) sequences from 50
      therapy-naive HIV-1-infected Nigerians. Phylogenetic analyses of RT revealed that
      the predominant viruses were CRF02_AG (57%), subtype G (26%), and CRF06_cpx
      (11%). Six of 35 (17%) individuals harbored primary mutations for RT inhibitors,
      including M41L, V118I, Y188H, P236L, and Y318F, and curiously three of the six
      were infected with CRF06_cpx. Therefore, CRF06_cpx drug-naive individuals had
      significantly more drug resistance mutations than the other subtypes (p = 0.011).
      By combining data on quasisynonymous codon bias with the influence of the
      differential genetic cost of mutations, we were able to predict some mutations,
      which are likely to predominate by subtype, under drug pressure. Some subtype
      specific polymorphisms occurred within epitopes for HLA B7 and B35 in the RT, and
      HLA A2 and A*6802 in PR, at positions implicated in immune evasion. Balanced
      polymorphism was also observed at predicted serine-threonine phosphorylation
      sites in the RT of subtype G viruses. The subtype-specific codon usage and
      polymorphisms observed suggest the involvement of differential pathways for drug
      resistance and host-driven viral evolution in HIV-1 CRF02_AG, subtype G, and
      CRF06_cpx, compared to subtype B. Subtype-specific responses to HIV therapy may
      have significant consequences for efforts to provide effective therapy to the
      populations infected with these HIV-1 subtypes.

PMID- 16910834
TI  - Association between HIV Type 1-specific T cell responses and CD4+ T cell counts
      or CD4+:CD8+ T cell ratios in HIV Type 1 subtype B infection in China.
AB  - CD4+ T cell counts and CD4+:CD8+ T cell ratios represent key determinants of HIV
      disease progression and infectivity. However, the relationship between the HIV-1
      specific cytotoxic T lymphocyte (CTL) response and these determinants has not
      been elucidated for all HIV-1B and HIV-1C proteins. In the present study,
      virusspecific T cell responses to HIV-1B and HIV-1C proteins were analyzed with
      interferon gamma (IFN-gamma) enzyme- linked immunospot (ELISpot) assays using
      synthetic overlapping peptides corresponding to naturally occurring HIV-1B and
      HIV-1C consensus sequences. For Gag/Gag p24/Gag p17, a correlation between T cell
      responses and CD4+ T cell count in HIV-1 clade B and clade C was seen: elevated T
      cell response resulted in higher CD4+ T cell production. A statistically
      significant correlation between the Pol-specific T cell response and CD4+ T cell
      counts was also found in HIV-1 subtype C. For all HIV-1B and HIV-1C proteins, a
      correlation between the HIV-1-specific T cell response and CD4+:CD8+ T cell
      ratios was found for Tat and Pol proteins. CD4+ T cell counts in patients with
      Tat and/or Rev T cell response were higher than in patients without Tat and/or
      Rev T cell response. We suggest that this correlation within HIV-1B and HIV-1C
      Gag p24/Gag p17 responses makes the Gag p24/Gag p17 region a potential vaccine
      candidate and that HIV-1-specific CTL epitopes toward Pol are important in
      controlling HIV-1 infection; we emphasize that future vaccination strategies
      should include these early antigens, Tat and Rev.

PMID- 16910835
TI  - Mucosal innate immune factors in the female genital tract are associated with
      vaginal HIV-1 shedding independent of plasma viral load.
AB  - Recent studies indicate that mucosal innate immune factors modulate HIV-1
      infection in vitro. Our interest was to examine the levels of innate mucosal
      factors for their potential association with HIV-1 shedding in the female genital
      tract. Vaginal lavages were collected from HIV-1-infected women who had vaginal
      viral loads (VVL) that were below, within, or above the 90% confidence interval
      (CI) predicted by their matched plasma viral loads. Innate immune factors
      [cathepsin D, lactoferrin (Lf), myeloid related protein (MRP)-8, MRP-8/14,
      secretory leukocyte protease inhibitor, and gp340], cytokines (IL-1beta and TNF
      alpha), and chemokines (MIP-1alpha, MIP-1beta, RANTES, and SDF-1alpha) were
      quantified by ELISA. Leukocyte levels were determined using a leukocyte reagent
      strip for urinalysis. Lf, MRP-8/14, gp340, and IL-1beta levels were significantly
      higher in vaginal lavages above the 90% CI and generally correlated with each
      other and with VVL. Leukocyte levels were significantly higher in the lavages
      that had virus shedding above the 90% CI and correlated strongly with Lf levels
      and VVL. In this group of women, these results suggest that the levels of certain
      innate immune factors are more closely associated with HIV-1 shedding in the
      genital mucosa than plasma virus concentrations.

PMID- 16910836
TI  - Genetic forms of HIV Type 1 in the former Soviet Union dominate the epidemic in
      Azerbaijan.
AB  - A total of 125 strains collected in Azerbaijan between 1999 and 2002 from HIV
      seropositives were genetically classified. Of 84 strains classified using HMA,
      91.6% were subtype A, 1.2% subtype B, and 7.1% untypeable. Of 41 strains analyzed
      using partial pol gene sequences, 90.2% were subtype A, 7.3% subtype B, and 2.4%
      CRF03_AB. Most sequenced A strains clustered with those circulating in countries
      of the former Soviet Union (FSU). Two of three sequenced B strains were from
      individuals who traveled to FSU clustering tightly with B strains from Nikolayev,
      Ukraine. CRF03_AB, characteristic of the 1996 epidemic in Kaliningrad, Russia,
      was sequenced from an individual who lived in Russia from 1995 until 2001. The
      HIV epidemic in Azerbaijan is concentrated in IDU and is closely connected to
      other such epidemics to the east based on genetics. Of the 41 sequenced strains,
      95% were close genetic relatives of HIV strains in IDU networks in the FSU.

PMID- 16910837
TI  - Molecular epidemiology of HIV Type 1 in preparation for a Phase III prime-boost
      vaccine trial in Thailand and a new approach to HIV Type 1 genotyping.
AB  - To characterize HIV-1 genotypes in candidate populations for a prime-boost phase
      III vaccine trial in Thailand, specimens from prevalent and incident HIV-1
      infections from a family planning clinic population in Rayong Province and a
      community cohort in Chon Buri Province, collected from 1998 to 2001, were
      genotyped. A new multiregion hybridization assay, MHAbce, capable of
      distinguishing HIV-1 CRF01_AE, subtype B, and subtype C and their recombinants,
      was developed and applied to prevalent infections. Most incident and selected
      prevalent infections were studied by complete genome sequencing. By MHAbce, 168
      of 194 prevalent infections were genotyped. Of these, 90.5% were CRF01_AE, 2.4%
      were subtype B, and 7.2% showed discordant or dual probe reactivity, indicative
      of recombination or dual infection, respectively. Among 23 incident infections,
      20 were sequenced. Eighteen CRF01_AE, one subtype B, and one CRF01/B recombinant
      strains were seen. Two CRF01/B and one CRF01/C recombinant were identified among
      selected prevalent infections. These results indicate that incident and prevalent
      HIV-1 infections in Rayong and Chon Buri during 1998-2001 were 90% CRF01_AE, 3%
      subtype B, and 7% either recombinant or dual. This study frames the genetic
      diversity of HIV-1 in these cohorts in their preparatory phase for the ongoing
      ALVACHIV (vCP1521) prime, AIDSVAX B/E boost, phase III vaccine trial and will
      provide a benchmark for interpretation and analysis.

PMID- 16910838
TI  - First case of HIV Type 1 subtype F among men who have sex with men in Colombia.
AB  - To study the molecular epidemiology of human immunodeficiency virus (HIV) strains
      among men who have sex with men (MSM), the main high-risk group for HIV infection
      in Colombia, 113 HIV-positive MSM subjects recruited in Bogota during the year
      2002 were genotyped. By heteroduplex mobility assay (env HMA) all samples were
      classified as subtype B. Partial sequencing of the protease and the reverse
      transcriptase (Pro/RT) regions performed on a random subset of 10 samples
      revealed that nine were classified as subtype B, and one sample was subtype F.
      The specimen that is subtype F in pol and subtype B in env is likely to be is
      either a recombinant or a dual infection. In this study, we identify the HIV F
      subtype for the first time in Colombia.

PMID- 16910839
TI  - HIV genetic diversity in Cameroon: possible public health importance.
AB  - To monitor the evolving molecular epidemiology and genetic diversity of HIV in a
      country where many distinct strains cocirculate, we performed genetic analyses on
      sequences from 75 HIV-1-infected Cameroonians: 74 were group M and 1 was group O.
      Of the group M sequences, 74 were classified into the following env gp41 subtypes
      or recombinant forms: CRF02 (n = 54), CRF09 (n = 2), CRF13 (n = 2), A (n = 5),
      CRF11 (n = 4), CRF06 (n = 1), G (n = 2), F2 (n = 2), and E (n = 1, CRF01), and 1
      was a JG recombinant. Comparison of phylogenies for 70 matched gp41 and protease
      sequences showed inconsistent classifications for 18 (26%) strains. Our data show
      that recombination is rampant in Cameroon with recombinant viruses continuing to
      recombine, adding to the complexity of circulating HIV strains. This expanding
      genetic diversity raises public health concerns for the ability of diagnostic
      assays to detect these unique HIV mosaic variants and for the development of
      broadly effective HIV vaccines.

PMID- 16910843
TI  - More on the need for comparative medicine.

PMID- 16910844
TI  - What is your diagnosis? Hypophosphatemic rickets as a consequence of
      hypovitaminosis D.

PMID- 16910840
TI  - Lack of correlation between SIV-Nef evolution and rapid disease progression in
      morphine-dependent nonhuman primate model of AIDS.
AB  - Six morphine-dependent and two control macaques were infected in an SIV/SHIV
      nonhuman primate model of AIDS. Three animals in the morphine group rapidly
      developed clinical disease and died within the timeframe of this study. The
      sequence evolution of nef in plasma virus was assessed at 4, 12, and 20 weeks
      postinfection. Cloned sequences were compared phylogenetically against each other
      as well as against the inoculum virus clones to determine the effect of morphine
      and rate of disease progression on diversity and divergence, respectively. Unlike
      our earlier studies of tat and env, nef evolution was not affected by morphine
      abuse or by rapid disease progression. The results suggest that although the
      evolution of other loci is inversely correlated to the onset and rate of clinical
      disease, differential evolution of nef is related neither to drug abuse nor to
      rapid progression within the first 20 weeks of infection.

PMID- 16910845
TI  - What is your diagnosis? Splenic torsion.

PMID- 16910846
TI  - ECG of the Month. Sinus arrhythmia in an African grey parrot.

PMID- 16910847
TI  - Theriogenology question of the month. Behavior problems in a stallion caused by a
      nephrolith.

PMID- 16910848
TI  - Efficacy of training in theriogenology as determined by a survey of
      veterinarians.
AB  - OBJECTIVE: To determine whether veterinarians perceive that theriogenology
      training at veterinary medical schools in North America and the Caribbean is
      adequate for achievement of theriogenology skills commonly used in private
      practice. PROCEDURES: A survey was mailed to members of the veterinary medical
      associations of Alabama, Kansas, Pennsylvania, and Washington. With regard to
      reproductive procedures in bovine, equine, porcine, small ruminant, camelid, and
      small animal species, veterinarians (predominantly practitioners) were asked to
      rate the importance of that procedure in their job and to assess their own degree
      of competency in that procedure at the time of their graduation from veterinary
      school. RESULTS: Procedures considered most valuable in practice were those that
      represent basic theriogenology education and training, such as transrectal
      palpation of cows and mares and interpretation of vaginal cytologic specimens in
      bitches. Dystocia management was a high priority in all species. Correlations
      between rankings for value in practice and competency at graduation were good,
      varying from 0.75 in cattle and 0.78 in horses to 0.98 in dogs and 1.0 in cats,
      small ruminants, and pigs. CONCLUSIONS: Analysis of these data suggests that
      appropriate theriogenology procedures are being taught in veterinary medical
      schools but perhaps not to the extent required to achieve adequate competency
      immediately at graduation. Issues requiring further investigation include the
      effect of tracking in the veterinary curriculum on theriogenology training,
      methods by which more students could receive greater practical exposure during
      theriogenology training, and the apparent relative lack of theriogenology
      training (including contraception) in small animals and exotic animals.

PMID- 16910849
TI  - Evaluation of the isoflurane-sparing effects of lidocaine and fentanyl during
      surgery in dogs.
AB  - OBJECTIVE: To evaluate the isoflurane-sparing effects of lidocaine and fentanyl
      administered by constant rate infusion (CRI) during surgery in dogs. DESIGN:
      Randomized prospective study. Animals-24 female dogs undergoing unilateral
      mastectomy because of mammary neoplasia. PROCEDURES: After premedication with
      acepromazine and morphine and anesthetic induction with ketamine and diazepam,
      anesthesia in dogs (n = 8/group) was maintained with isoflurane combined with
      either saline (0.9% NaCl) solution (control), lidocaine (1.5 mg/kg [0.68 mg/lb],
      IV bolus, followed by 250 microg/kg/min [113 microg/lb/min], CRI), or fentanyl (5
      microg/kg [2.27 microg/lb], IV bolus, followed by 0.5 microg/kg/min [0.23
      microg/lb/min], CRI). Positive-pressure ventilation was used to maintain
      eucapnia. An anesthetist unaware of treatment, endtidal isoflurane (ETiso)
      concentration, and vaporizer concentrations adjusted a nonprecision vaporizer to
      maintain surgical depth of anesthesia. Cardiopulmonary variables and ETiso values
      were monitored before and after beginning surgery. RESULTS: Heart rate was lower
      in the fentanyl group. Mean arterial pressure did not differ among groups after
      surgery commenced. In the control group, mean +/- SD ETiso values ranged from
      1.16 +/- 0.35% to 1.94 +/- 0.96%. Fentanyl significantly reduced isoflurane
      requirements during surgical stimulation by 54% to 66%, whereas the reduction in
      ETiso concentration (34% to 44%) observed in the lidocaine group was not
      significant. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of fentanyl
      resulted in greater isoflurane sparing effect than did lidocaine. However, it
      appeared that the low heart rate induced by fentanyl may partially offset the
      improvement in mean arterial pressure that would be expected with reduced
      isoflurane requirements.

PMID- 16910850
TI  - Intramuscular administration of a low dose of ACTH for ACTH stimulation testing
      in dogs.
AB  - OBJECTIVE: To compare adrenal gland stimulation achieved following administration
      of cosyntropin (5 microg/kg [2.3 microg/lb]) IM versus IV in healthy dogs and
      dogs with hyperadrenocorticism. DESIGN: Clinical trial. Animals-9 healthy dogs
      and 9 dogs with hyperadrenocorticism. PROCEDURES: In both groups, ACTH
      stimulation was performed twice. Healthy dogs were randomly assigned to receive
      cosyntropin IM or IV first, but all dogs with hyperadrenocorticism received
      cosyntropin IV first. In healthy dogs, serum cortisol concentration was measured
      before (baseline) and 30, 60, 90, and 120 minutes after cosyntropin
      administration. In dogs with hyperadrenocorticism, serum cortisol concentration
      was measured before and 60 minutes after cosyntropin administration. RESULTS: In
      the healthy dogs, serum cortisol concentration increased significantly after
      administration of cosyntropin, regardless of route of administration, and serum
      cortisol concentrations after IM administration were not significantly different
      from concentrations after IV administration. For both routes of administration,
      serum cortisol concentration peaked 60 or 90 minutes after cosyntropin
      administration. In dogs with hyperadrenocorticism, serum cortisol concentration
      was significantly increased 60 minutes after cosyntropin administration, compared
      with baseline concentration, and concentrations after IM administration were not
      significantly different from concentrations after IV administration. CONCLUSIONS
      AND CLINICAL RELEVANCE: Results suggest that in healthy dogs and dogs with
      hyperadrenocorticism, administration of cosyntropin at a dose of 5 microg/kg, IV
      or IM, resulted in equivalent adrenal gland stimulation.

PMID- 16910851
TI  - Disease prevalence among dogs and cats in the United States and Australia and
      proportions of dogs and cats that receive therapeutic diets or dietary
      supplements.
AB  - OBJECTIVE: To estimate disease prevalence among dogs and cats in the United
      States and Australia and proportions of dogs and cats that receive therapeutic
      diets or dietary supplements. DESIGN: Telephone survey. Sample Population-Dog and
      cat owners located in 5 geographic areas. PROCEDURES: A telephone survey was
      administered to dog and cat owners. RESULTS: Of 18,194 telephone calls that were
      made, 1,104 (6%) were to individuals who owned at least 1 dog or cat and agreed
      to participate. Information was collected for 635 dogs and 469 cats. Only 14 (1%)
      respondents indicated that their pet was unhealthy, but 176 (16%) indicated that
      their pets had 1 or more diseases. The most common diseases were musculo
      skeletal, dental, and gastrointestinal tract or hepatic disease. Many owners (n =
      356) reported their pets were overweight or obese, but only 3 reported obesity as
      a health problem in their pets. Owners of 28 (2.5%) animals reported that they
      were feeding a therapeutic diet, with the most common being diets for animals
      with renal disease (n = 5), reduced-calorie diets (5), and reduced-fat diets (4).
      Owners of 107 of 1,076 (9.9%) animals reported administering dietary supplements
      to their pets. Multivitamins (n = 53 animals), chondroprotective agents (22), and
      fatty acids (13) were the most common dietary supplements used. CONCLUSIONS AND
      CLINICAL RELEVANCE: Results suggest that most dogs and cats reported by their
      owners to have a health problem were not being fed a therapeutic diet. In
      addition, the rate of dietary supplement use was lower than that reported for
      people.

PMID- 16910852
TI  - Evaluation of ilial screw loosening after triple pelvic osteotomy in dogs: 227
      cases (1991-1999).
AB  - OBJECTIVE: To investigate factors influencing screw loosening after triple pelvic
      osteotomy (TPO) and ischial wire stabilization of the acetabular segment. DESIGN:
      Retrospective case series. Animals-227 dogs with congenital hip dysplasia or
      subluxated hip joints. PROCEDURES: Medical records and radiographs of 227 dogs
      that underwent 332 TPO procedures were evaluated, and data pertaining to screw
      type, plate position, sacral screw engagement, use of ischial interfragmentary
      wires, and pelvic alignment were assessed for associations with screw loosening.
      RESULTS: Complications developed in 96 of the 332 (29%) procedures. Cancellous
      screws without sacral engagement were associated with the lowest frequency (6%)
      of loosening, compared with cancellous and cortical screws engaging the sacrum
      and cortical screws that did not engage the sacrum. Frequency of screw loosening
      increased when cortical or cancellous screws engaged the sacrum and when cortical
      screws were used. In dogs that had surgery bilaterally, the first limb on which
      TPO was performed had a higher frequency of screw loosening than the second limb.
      Pelvic alignment loss was greatest (5.4 degrees ) when the 3 most cranial screws
      were loosened. Loss of pelvic alignment was significantly different between dogs
      that underwent surgery and had complications and those that underwent surgery and
      did not have complications in association with loosening of 1, 2, and 3 screws.
      CONCLUSIONS AND CLINICAL RELEVANCE: TPO screw loosening was multifactorial and
      related to stability of the affected ilium, screw type, and screw position.
      Placing cancellous screws that do not engage the sacrum in pelvic osteotomy plate
      positions 1 through 3 may decrease the number of screws that loosen.

PMID- 16910854
TI  - Sodium iodide I 131 treatment of dogs with nonresectable thyroid tumors: 39 cases
      (1990-2003).
AB  - OBJECTIVE: To determine outcome for dogs with nonresectable thyroid carcinomas
      treated with sodium iodide I 131 and identify factors associated with outcome.
      DESIGN: Retrospective case series. Animals-39 dogs. PROCEDURES: A definitive or
      presumptive diagnosis of thyroid tumor was made on the basis of cytologic or
      histologic examination, abnormal accumulation of sodium pertechnetate Tc 99m
      during scintigraphy, or both, and dogs were treated with sodium iodide I 131.
      Dogs with cervical thyroid tumors were evaluated 3 to 6 weeks after 131I therapy,
      and residual tumor was resected when feasible. RESULTS: Prior to 131I therapy, 32
      dogs had a solitary mass and 7 had metastases; 21 were hyperthyroid, 16 were
      euthyroid, and 2 were hypothyroid. Median survival time for dogs with local or
      regional tumors (ie, stage II or III) was significantly longer (839 days) than
      median survival time for dogs with metastasis (366 days). Tumor site (cervical vs
      ectopic), dose of sodium iodide I 131, age, body weight, treatment (131I therapy
      alone vs 131I therapy followed by surgery), and serum T4 concentration prior to
      131I therapy were not significantly associated with survival time. Three dogs
      died of radioiodine-associated myelosuppression within 3 months after treatment,
      but no specific factor associated with development of toxicosis was identified.
      CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that 131I therapy may
      result in prolonged survival times in dogs with nonresectable thyroid tumors,
      regardless of serum thyroxine concentration prior to treatment. Dogs undergoing
      131I therapy should be monitored for signs of bone marrow suppression.

PMID- 16910855
TI  - Disorders of the infraspinatus tendon and bursa in three horses.
AB  - CASE DESCRIPTION: 3 horses with penetrating wounds to the shoulder area were
      examined because of forelimb lameness. CLINICAL FINDINGS: All horses had physical
      examination findings (decreased cranial phase of the stride, swelling in the
      shoulder region, and signs of pain on manipulation of the shoulder) that were
      suggestive of problems in the upper portion of the forelimb. Injury to the biceps
      tendon or bursa was the primary differential diagnosis in each instance, but no
      abnormalities involving those structures were found. Radiographic and
      ultrasonographic imaging revealed injuries to the caudal eminence of the greater
      tubercle of the humerus, the infraspinatus tendon, and the infraspinatus bursa.
      Examination with ultrasound was more sensitive than radiography at detecting both
      osseous and soft tissue changes. TREATMENT AND OUTCOME: All 3 horses responded
      favorably to treatment with antimicrobials and non-steroidal anti-inflammatory
      drugs. Although initial response to standing lavage was favorable in 1 horse,
      endoscopic lavage was later required. Standing removal of fracture fragments was
      performed in 2 horses. Ultrasonographic imaging was helpful in monitoring the
      response to treatment and changes in the affected structures. All 3 horses
      eventually became sound after treatment. CLINICAL RELEVANCE: Infraspinatus
      bursitis and tendonitis should be included in the differential diagnoses of
      horses with shoulder lameness. Diagnosis and monitoring should include
      ultrasonographic monitoring. The prognosis for return to soundness after
      appropriate treatment appears to be good.

PMID- 16910856
TI  - Efficacy of tulathromycin for treatment of cattle with acute ocular Moraxella
      bovis infections.
AB  - OBJECTIVE: To evaluate the clinical efficacy of a single injection of
      tulathromycin, compared with saline (0.9% NaCl) solution-treated control calves,
      for treatment of induced infectious bovine keratoconjunctivitis in calves.
      DESIGN: Clinical trial. ANIMALS: 30 Holstein bull calves ranging from 5 to 6
      months old and 75 to 200 kg (165 to 440 lb) with no history of Moraxella bovis
      infections, no history of M bovis vaccination, and negative results for M bovis
      on 3 consecutive ocular bacterial cultures. PROCEDURES: Both eyes of each calf
      were infected with 1 X 10(10) colony-forming units of piliated M bovis for 3
      consecutive days prior to the trial. On day 0, ocular lesion scores were
      determined for each calf and the calves were weighed and assigned to a treatment
      (2.5 mg/kg [1.14 mg/lb] of body weight, SC) or control group according to a
      stratified random allocation based on weight and lesion score. Eyes were stained
      with fluorescein and photographed daily to record healing. Eyes were evaluated
      bacteriologically for M bovis on days 0 to 6 and at 3-day intervals thereafter.
      RESULTS: Median time to ulcer resolution in calves treated with tulathromycin was
      9.1 days. More than 50% of control calves still had ulcers at the end of the
      trial (21 days). Moraxella sp was isolated less often from the eyes of treated
      calves than from the control calves. By day 10, the treated calves had lower
      ocular lesion scores than control calves. CONCLUSIONS AND CLINICAL RELEVANCE: A
      single dose of tulathromycin (SC) was an effective treatment of calves with
      experimentally induced infectious bovine keratoconjunctivitis. The long serum
      half-life of tulathromycin, along with the results of this trial, suggests that
      tulathromycin may be a rational choice as a single-injection treatment for
      infectious bovine keratoconjunctivitis.

PMID- 16910858
TI  - Acquired cervical scoliosis attributed to Parelaphostrongylus tenuis infection in
      an alpaca.
AB  - CASE DESCRIPTION: A 2-year-old alpaca was evaluated because of acute onset of
      cervical scoliosis. CLINICAL FINDINGS: Physical examination revealed severe
      scoliosis of the caudal portion of the cervical vertebral column with a C-shaped
      curvature to the right side. No gait deficits were observed. Cervical radiography
      confirmed severe curvature of C4 to C6 but did not reveal any bony changes.
      Cerebrospinal fluid had high total protein concentration and extremely high
      nucleated cell count with a high proportion of eosinophils, suggesting parasitic
      infection. TREATMENT AND OUTCOME: The alpaca was treated for suspected
      parelaphostrongylosis with ivermectin, fenbendazole, flunixin, vitamin E,
      thiamine, physical therapy, and a custom-made neck brace. The alpaca's condition
      continued to deteriorate, and it developed tetraparesis and ataxia and was
      euthanized after approximately 1 month. Microscopic evaluation of the cervical
      spinal cord revealed marked vacuolar changes in the left medial portion of the
      ventral funiculus, mild lymphoplasmacytic infiltration, and multifocal
      granulomas. The lesions were continuous from C1 to C7 and were compatible with
      parasite migration. CLINICAL RELEVANCE: To the authors' knowledge, this is the
      first report of acquired scoliosis in an alpaca, which appears to represent an
      unusual manifestation of parelaphostrongylosis that was reported in horses.

PMID- 16910860
TI  - A novel vascular endothelial growth factor receptor 2 inhibitor, SU11248,
      suppresses choroidal neovascularization in vivo.
AB  - AIM: An oral, multitargeted receptor tyrosine kinase inhibitor, SU11248, inhibits
      vascular endothelial growth factor receptor 2 (VEG FR2, kinase domain receptor
      F1K1), platelet-derived growth factor receptor, stem cell factor receptor (Kit),
      and fetal liver tyrosine kinase 3. In this study, we administered SU11248 beyond
      the completion of an experimental choroidal neovascularization (CNV) model to
      determine whether CNV growth can be inhibited in vivo. METHODS: C57B6J mice were
      treated with daily oral administration (40, 80, and 150 mg/kg) of SU11248 during
      5 days after diode laser endophotocoagulation and subjected to angiographic
      examination and histological analysis. RESULTS: Intensity of fluorescein leakage
      from the experimental CNV decreased significantly compared to the control eyes.
      Histological study also revealed that the volume of CNV membrane was
      significantly reduced in the SU11248-treated eyes. CONCLUSIONS: Oral
      administration of this compound is potentially beneficial in treating CNV caused
      by age-related macular degeneration (AMD) and other causal diseases. Considering
      the tolerance the clinical studies for malignant tumors previously demonstrated,
      further studies to evaluate the clinical efficacy of the drug for AMD might be
      indicated.

PMID- 16910861
TI  - The effect of unoprostone isopropyl on Ca2+ release-activated Ca2+ currents in
      cultured monkey trabecular meshwork cells and ciliary muscle cells.
AB  - PURPOSE: The aim of this study was to investigate the effect of unoprostone
      isopropyl (UF- 021) on Ca2+ release-activated Ca2+ (CRAC) currents in cultured
      monkey trabecular meshwork (TM) cells and to compare the inhibitory effects on
      CRAC in cultured monkey ciliary muscle (CM) cells. METHODS: Both TM and CM cells
      were isolated from monkey eyes, and each was grown in monolayer cell cultures. To
      measure changes in intracellular Ca2+ concentrations ([Ca2+]i), both types of
      cells were labeled with fluo-3 acetoxymethylester (AM) as a calcium indicator for
      30 min at 25 degrees C and imaged with a confocal laser scanning microscope.
      After depletion of the intracellular Ca2+ stores with 1 microM thapsigargin and 1
      mM EGTA containing Ca2+-free external solution, exposure to 2 mM Ca2+-containing
      external solution induced a sudden increase in [Ca2+]i, which was defined as the
      CRAC current. RESULTS: In both TM and CM cells, CRAC currents were observed and
      were well suppressed by unoprostone-free acid (M1 metabolite). In the TM cells, 3
      microM M1 metabolite suppressed the CRAC current. In contrast, in the CM cells,
      the CRAC current was suppressed by 100 microM M1 metabolite, but not by 10 microM
      or less. The half maximal inhibition concentration of M1 metabolite was 24.8+/
      9.8 microM in TM cells and 183+/-30.6 microM in CM cells. CONCLUSIONS: These
      findings indicate that there are CRAC channels in both TM and CM cells, and the
      influx of [Ca2+]i through the CRAC channels is suppressed by M1 metabolite. The
      inhibitory effect of M1 metabolite on CRAC currents was more prominent in TM
      cells than in CM cells. Suppression of the Ca2+ influx through CRAC channels by
      M1 metabolite is thought to regulate muscle tone in TM and CM cells. Therefore,
      CRAC inhibition by M1 metabolite may contribute to reduction of intraocular
      pressure.

PMID- 16910862
TI  - Pharmacokinetics of chlorhexidine gluconate 0.02% in the rabbit cornea.
AB  - PURPOSE: The aim of this study was to determine the pharmacokinetic parameters of
      chlorhexidine gluconate (CHG) in the rabbit cornea. METHODS: Each eye of 16 New
      Zealand white rabbits were topically instilled with 50 microL of CHG 0.02% eye
      drops twice with a 5-min interval. Four (4) corneas of 2 rabbits were harvested
      at each time point. The concentration of CHG in the cornea was determined with
      high-performance liquid chromatography (HPLC) and 387 software to simulate the
      pharmacokinetic parameters. RESULTS: The concentration of CHG in the cornea
      displayed an open two-compartment model. Tmax was 13.75 min, Cmax 0.713
      microg.g1, clearance rate 1.64 microg.g-1.min-1, and t1/2alpha, t1/2beta, and
      t1/2ka was 2.65, 48.72, and 2.67 min, respectively. CONCLUSIONS: The
      concentration of CHG in the rabbit cornea could be determined by means of HPLC.
      The maximum concentration of CHG in the corneal tissue was much higher than the
      trophozoite minimum amoebicidal concentration (TMAC) in vitro.

PMID- 16910863
TI  - Vitreal pharmacokinetics of dipeptide monoester prodrugs of ganciclovir.
AB  - PURPOSE: The aim of this study was to determine vitreal pharmacokinetics of a
      series of dipeptide monoester ganciclovir (GCV) prodrugs and to study their
      interaction with the retinal peptide transporter. METHODS: New Zealand albino
      male rabbits were selected as the animal model. Ocular microdialysis technique
      was employed to delineate the pharmacokinetics of GCV, L-valine-GCV and dipeptide
      monoester GCV prodrugs (L-valine-L-valine, L-tyrosine-L-valine, and L-glycine- L
      valine) following intravitreal administration. RESULTS: Val-GCV and Val-Val-GCV
      inhibited retinal uptake of [3H]Gly-Sar by 43% and 37%, respectively, suggesting
      that these prodrugs may be substrates of the retinal peptide transport system.
      Val-GCV and Gly-Val-GCV were observed to be the most stable GCV prodrugs in
      vitreous humor. All GCV prodrugs were rapidly converted to GCV in retinal
      homogenates. Vitreal pharmacokinetic studies suggest that Val-GCV and Val-Val-GCV
      are rapidly eliminated from the vitreous chamber, compared to GCV, whereas Gly
      Val-GCV is eliminated at a much slower rate. Retinal GCV concentrations generated
      from all three prodrugs, at the end of 5 h, were almost equivalent and were
      almost twice that following intravitreal administration of GCV. Gly-Pro, however,
      did not demonstrate any effect on retinal uptake of Val-GCV or Gly-Val-GCV.
      CONCLUSIONS: Considering retinal GCV concentrations generated and vitreal
      pharmacokinetic profiles, Gly-Val-GCV appears to be a lead candidate for further
      in vivo evaluation against human cytomegalovirus (HCMV) retinitis.

PMID- 16910865
TI  - Triamcinolone acetonide-induced ocular hypertension.
AB  - PURPOSE: The aim of this study is to report on the clinical course of a patient
      showing markedly increased intraocular pressure (IOP) caused by intravitreal
      triamcinolone acetonide. METHODS: A 33-year-old patient received an intravitreal
      injection of approximately 20 mg of triamcinolone acetonide (TA) as treatment of
      otherwise therapy-resistant uveitis. She experienced an IOP rise to values over
      40 mmHg for a period for more than 3 months, despite maximal antiglaucomatous
      medical therapy. Peak IOP was 55 mmHg. RESULTS: Neither confocal scanning laser
      tomography nor qualitative assessment of optic disc photographs nor perimetry
      showed development of glaucomatous changes. Scanning laser polarimetry of the
      retinal nerve fiber layer suggested a slight loss in the nasal upper fundus
      quadrant. CONCLUSIONS: Relatively young patients with a pronounced TA-induced
      rise in IOP, unresponsive to maximal antiglaucomatous medication, may not
      necessarily undergo antiglaucomatous surgery if the rise in IOP does not last
      longer than approximately 3 months.

PMID- 16910864
TI  - Vitreous concentration of topically applied brimonidine-purite 0.15%.
AB  - PURPOSE: The aim of this study was to determine the vitreous brimonidine
      concentration of topically applied brimonidine-Purite 0.15%. METHODS: Patients
      scheduled for a pars plana vitrectomy were invited to participate in this study
      after institutional review board (IRB) approval was obtained. Each patient was
      asked to apply brimonidine-Purite (0.15%) drops in the designated eye either
      every 12 h (b.i.d.; 9 patients) or every 8 h (t.i.d.; 10 patients) for the 2
      weeks proceeding scheduled surgery. The importance of the last topical dose being
      12 h (b.i.d. group) or 8 h (t.i.d. group) before the scheduled surgery, was
      emphasized. Four (4) patients served as controls and did not receive any drops.
      Vitreous (approximately 0.5-1.0 mL) was aspirated prior to opening the infusion
      line. Specimens were frozen at -68 degrees C until analyzed. RESULTS: In the
      b.i.d. group, the mean concentration of brimonidine was 16.74 nM+/-10.33 standard
      deviation (range, 0.42-34.68 nM; median, 16.38); in the t.i.d. group, the mean
      concentration of brimonidine was 19.16 nM+/-15.40 standard deviation (range, 0.22
      39.48 nM; median, 16.98). A significant difference was observed between the (no
      drug) control vitreous brimonidine levels and b.i.d. or t.i.d. vitreous levels
      (P<0.01, <0.01, respectively; n=4, 9, and 10, respectively); and in brimonidine
      levels between t.i.d. phakic patients and t.i.d. patients with posterior chamber
      lens (P=0.04; n=4 and 6, respectively). CONCLUSIONS: Brimonidine-Purite 0.15%,
      topically applied b.i.d. or t.i.d. for 2 weeks prior to collection, acquired
      vitreous levels of brimonidine at or above the 2-nM concentration known to
      activate the neuroprotective alpha-2 receptor in animals.

PMID- 16910866
TI  - Evaluation of 0.4% ketorolac tromethamine ophthalmic solution versus 0.5%
      ketorolac tromethamine ophthalmic solution after phacoemulsification and
      intraocular lens implantation.
AB  - PURPOSE: The aim of this study was to compare the effectiveness and patient
      tolerance of 0.4% ketorolac tromethamine ophthalmic solution and 0.5% ketorolac
      tromethamine ophthalmic solution after routine phacoemulsification and lens
      implantation. SETTING: The setting for this study was the Storm Eye Institute and
      Magill Research Center for Vision Correction, Medical University of South
      Carolina (Charleston, SC). METHODS: This work was a prospective, double-masked
      study that included 40 eyes of 40 patients randomly assigned to receive topical
      treatment with 0.4% ketorolac or 0.5% ketorolac, starting 15 min prior to routine
      phacoemulsification and foldable posterior chamber intraocular lens implantation.
      Following the procedure, patients were instructed to use the assigned treatment
      agent 4 times a day after surgery for 1 week and twice a day for 3 weeks, when
      drops were discontinued. Slit-lamp examination, intraocular pressure (IOP), laser
      cell and flare measurements, and subjective patient tolerance were evaluated
      postoperatively at 1, 7, and 30 d. Comparisons between the 2 groups were made at
      each visit, as well as comparisons to baseline. A P=value less than .05 was
      considered statistically significant. RESULTS: At day 1, a higher percentage of
      patients (70% vs. 40%) reported symptoms (mainly foreign body sensation and
      stinging/burning) in the 0.5% ketorolac group, compared to the 0.4% ketorolac
      group. No significant differences were found between the 2 groups over time
      regarding best-corrected visual acuity (BCVA), IOP, slit-lamp assessment of
      cells, and cell and flare measured using the laser cell/flare meter. CONCLUSIONS:
      Treatment with 0.4% ketorolac tromethamine ophthalmic solution is as effective as
      0.5% ketorolac tromethamine ophthalmic solution in reducing inflammation after
      routine cataract surgery. Patients reported less discomfort using 0.4% ketorolac.

PMID- 16910867
TI  - Antibiotic effects of WP-0405, a thermo-setting ofloxacin gel, on methicillin
      resistant Staphylococcus aureus keratitis in rabbits.
AB  - PURPOSE: The chemotherapeutic effects and pharmacokinetics properties of WP-0405
      (a thermo-setting in situ 0.3% ofloxacin-containing ophthalmic gel) and ofloxacin
      (a conventional 0.3% ofloxacin solution) on methicillin-resistant Staphylococcus
      aureus (MRSA) keratitis were compared in a rabbit model. METHOD: The single
      instillation pharmacokinetics of WP-0405 and ofloxacin in the cornea, aqueous
      humor, conjunctiva, and iris-ciliary body were determined in normal rabbit eyes.
      To compare the duration of antimicrobial action, WP-0405 or ofloxacin was
      instilled oncedaily in an early-treatment model of keratitis, and corneas were
      either removed immediately or 4 or 8 h postinstillation. In another experiment,
      WP-0405 was instilled two or three times daily to compare its antibiotic efficacy
      with three-times daily instillation of ofloxacin in the same early-treatment
      model of keratitis; corneas were then removed after determining the extent of the
      abscess area. In another experiment, WP-0405 was instilled four or eight times
      daily to compare its effects with eight-times daily instillation of ofloxacin in
      a late-treatment model of keratitis, and corneas were removed. The number of
      viable bacteria in the corneas was determined in all experiments. RESULTS: Cmax
      and AUC0- in tissues treated with WP-0405 were 1.5-3.4-fold and 1.8-2.9-fold
      greater than those treated with ofloxacin, respectively. WP-0405 significantly
      reduced the number of viable bacteria for up to 8 h after a single instillation.
      WP-0405 not only significantly reduced the number of viable bacteria, but also
      the size of the abscess area at the same frequency of instillation. When compared
      to ofloxacin, WP-0405 exhibited an approximately equivalent antibiotic effect,
      with fewer administrations. CONCLUSIONS: As a result of its pharmacokinetics, WP
      0405 had a more potent, longer-acting antibiotic effect than did ofloxacin.
      Furthermore, because of its lower required instillation frequency, which would
      improve patient compliance, WP-0405 has great potential therapeutic benefits.

PMID- 16910868
TI  - Comparison of toxicological profiles of benzalkonium chloride and polyquaternium
      1: an experimental study.
AB  - PURPOSE: The aim of this study was to compare, in vivo on a rat model, two
      different preservatives- benzalkonium chloride (BAC) and polyquaternium-1 (PQ-1)
      using new experimental approaches. METHODS: Thirty (30) eyes of 15 male Lewis
      rats were used in this study. Rats were randomly divided into five groups
      instilled twice a day for 11 days with eye drops containing different
      concentrations of preservatives, 0.1% BAC, 0.5% BAC, 0.1% PQ-1, 0.5% PQ-1, and
      balanced salt solution (BSS) as a control. The ocular surface toxicity of these
      two preservatives was investigated using new in vivo experimental approaches.
      Slit-lamp examination, the fluorescein test, the red phenol test, impression
      cytology, and in vivo corneal confocal microscopy were used to evaluate the rat
      ocular surface after preservative instillation. Histology sections and
      immunohistochemistry were also examined to confirm these results. RESULTS:
      Compared to PQ-1, BAC consistently and dramatically altered the
      corneoconjunctival surface as evaluated by slit-lamp examination, the fluorescein
      test, impression cytology, in vivo confocal microscopy, and histology. The 0.5%
      BAC solution also significantly decreased tear production compared to the
      control. Although 0.5% PQ-1 significantly decreased goblet cell density in
      comparison to the control, and some abnormalities were observed with in vivo
      confocal microscopy, no statistically significant differences were observed
      between these two groups using the tear production test, slit-lamp and
      fluorescein evaluation, or histology. CONCLUSION: Using an acute rat model of
      ocular toxicity by comparing preservatives at high concentrations, we
      demonstrated in vivo that high doses of PQ-1 were much less toxic than BAC. In
      vivo confocal microscopy and impression cytology are new promising experimental
      approaches to studying the rat corneoconjunctival surface, particularly in the
      field of ocular surface toxicity.

PMID- 16910870
TI  - European Thyroid Association: 2006 in Naples.

PMID- 16910869
TI  - Corneal toxicity of cell-penetrating peptides that inhibit Herpes simplex virus
      entry.
AB  - Cell-penetrating peptides (CPPs) inhibit Herpes simplex virus entry at low
      micromolar concentrations and may be useful either as prophylactic or therapeutic
      agents for herpetic keratitis. The aim of this study was to assess the in vitro
      and in vivo toxicity of three CPPs-EB, TAT-C, and HOM (penetratin)-for the
      cornea. Incubation of primary (HK320) or immortalized (THK320) human keratocytes
      with the EB peptide (up to 100 microM), bHOMd (up to 200 microM), or TAT-C (up to
      400 microM) resulted in no evidence of toxicity using a formazan dye-reduction
      assay. Similar results were obtained with a human trabecular meshwork cell line
      (TM-1), primary human foreskin fibroblasts (DP-9), Vero, and HeLa cells with EB
      and TATC. The bHOMd peptide showed some toxicity in Vero and HeLa cells, with
      CC50 values of 70 and 93 microM, respectively. The EB peptide did not inhibit
      macromolecular synthesis in Vero cells at concentrations below 150 microM,
      although cell proliferation was blocked at concentrations of EB above 50 microM.
      In vivo toxicity was assessed by applying peptides in Dulbecco's modified Eagle's
      medium to the cornea 4 times daily for 7 d. At concentrations 1000 times the IC50
      values, the EB and bHOM peptides showed no toxicity, whereas TAT-C caused some
      mild eyelid swelling. Some slight epithelial cell sloughing was seen with the
      bKLA peptide in vivo. These results suggest that these CPPs-and EB in particular
      have a favorable toxicity profile, and that further development is warranted.

PMID- 16910871
TI  - Cloning and characterization of a novel isoform of iodotyrosine dehalogenase 1
      (DEHAL1) DEHAL1C from human thyroid: comparisons with DEHAL1 and DEHAL1B.
AB  - The human iodotyrosine dehalogenase 1 (DEHAL1) gene is composed of six exons. Two
      isoforms (DEHAL1 and DEHAL1B) have been published in GenBank, both of which have
      a nitroreductase domain and arise from differential splicing in exon 5. We
      recently showed that the DEHAL1 isoform is a transmembrane protein that
      efficiently catalyzes the NADPH-dependent deiodination of mono (L-MIT) and
      diiodotyrosine (L-DIT) in human embryonic kidney-293 (HEK293) cells. In the
      present study, we establish the existence of a new transcript, DEHAL1C, in the
      human thyroid with a terminal exon that lacks in the DEHAL1 transcript. This exon
      is the complete exon 5, which is spliced in the DEHAL1B mRNA variant. These two
      variants encode proteins with differing C-terminal domains. Using quantitative
      reverse transcription polymerase chain reaction, we found that the expression of
      the mRNA of DEHAL1C and DEHAL1B was lower than that of DEHAL1 mRNA in the
      thyroid. We also observed that human DEHAL1B and DEHAL1C proteins are rapidly
      degraded in stably transfected HEK293 cells, unlike the DEHAL1 protein, and that
      exposure to the proteasome inhibitor MG132 resulted in accumulation of these
      proteins that was markedly time- and concentration-dependent. These findings show
      that the cytoplasmic tail could play a role in the stability of the protein.

PMID- 16910872
TI  - ClC-5 does not affect megalin expression and function in the thyroid.
AB  - Megalin is an endocytic receptor responsible for thyroglobulin (Tg) transcytosis,
      a process that favors hormone release. Accordingly, megalin KO mice have primary
      hypothyroidism. In the kidney, megalin expression is reduced when the gene
      encoding the chloride transporter ClC-5 is mutated. We investigated whether
      megalin expression and function in the thyroid are affected by ClC-5 using a ClC
      5 KO mouse model. By Western blotting, ClC-5 was found in thyroid tissue extracts
      of WT, but not of ClC-5 KO mice. In addition, ClC-5 was found to be expressed by
      cultured thyroid cells (FRTL-5). The thyroid size, weight, and histology were
      similar in ClC- 5 KO and WT mice, as were the amounts of megalin in thyroid
      extracts. Accordingly, serum Tg, a measure of megalin-mediated transcytosis, was
      similar in WT and ClC-5 KO mice, suggesting that megalin function was unaffected.
      Thus, unlike in megalin KO mice, in ClC-5 KO mice thyroid function was unchanged,
      as indicated by the normal serum FT4 and TSH. We concluded that in the thyroid,
      unlike in the kidney, ClC-5 does not affect megalin expression and function,
      suggesting that megalin is differentially regulated in these two organs.

PMID- 16910873
TI  - Exercise performance in young and middle-aged female patients with subclinical
      hyperthyroidism.
AB  - Subclinical hyperthyroidism (SH) may be responsible for many cardiovascular
      changes, including an impaired exercise performance. The aim of our study was to
      evaluate the response to the treadmill cardiopulmonary test in patients with SH.
      We studied 14 female patients from our endocrine clinic with exogenous SH, free
      from cardiovascular diseases, with mean age of 38.6 +/- 10.2 years, body mass
      index (BMI) of 24.4 +/- 4.0 kg/m(2), and disease duration of 4.9 +/- 4.9 years.
      The mean serum thyrotropin (TSH) was 0.03 +/- 0.03 mU/L, serum free thyroxine
      (FT(4)), 1.72 +/- 0.21 ng/dL, and serum triiodothyronine level, 137 +/- 32 ng/dL.
      The control group comprised 15 euthyroid, healthy women, with mean age of 35.4 +/
      7.4 years and BMI of 27.3 +/- 5.9 kg/m(2). Both groups had a sedentary lifestyle
      and underwent the cardiopulmonary test using a treadmill with the Balke protocol.
      Gas concentrations and the respiratory outflow were measured and the
      electrocardiogram (ECG) was registered in real time. We calculated the minute
      ventilation (V(E)), the oxygen consumption (peak VO(2)), the carbonic gas
      exhalation (peak VCO(2)) and the anaerobic threshold (AT). The heart rate (HR) at
      rest (90.9 +/- 15.7 versus 78.9 +/- 8.7 beats per minute; p = 0.03) was higher in
      the patients from our clinic. There was no difference between groups regarding
      age, BMI, fat percentage, blood pressure, peak HR, exercise duration, mean
      treadmill peak inclination, V(E), peak VO(2), peak VCO(2), and AT. There was no
      correlation between peak VO(2) and FT(4), TSH, or disease duration. Our results
      show that exercise capacity in young and middle-aged female patients is not
      significantly affected by exogenous SH.

PMID- 16910874
TI  - Phosphorylation of heat shock protein-90 by TSH in FRTL-5 thyroid cells.
AB  - CONTEXT: Although it is well established that thyrotropin (TSH) initiates signal
      transduction systems resulting in protein kinase(s) activation, the
      phosphorylated targets have not been fully characterized. OBJECTIVE/DESIGN: In
      FRTL-5 thyroid cells, we used two-dimensional (2D) gel images of silver-stained
      proteins isolated from FRTL- 5 thyroid cells following TSH stimulation to
      identify potential phosphorylation targets. RESULTS: We characterized a 90 kDa
      protein that had undergone a pH shift and subsequently identified it as heat
      shock protein-90 (hsp-90) following in-gel trypsin digestion and mass
      spectroscopy. This was confirmed by Western blot using a monoclonal antibody
      against hsp-90. Western blot analysis of the 2D gel images using a polyclonal
      antibody directed at phosphoserine/threonine sites showed that TSH induced the
      phosphorylation of hsp-90. Western blotting of hsp-90 following stimulators of
      the signal transduction systems mediated by TSH indicated that TSH-mediated hsp
      90 phosphorylation occurs through protein kinases A and C. CONCLUSION: In
      summary, we have demonstrated that TSH action stimulates the phosphorylation of
      hsp-90 in FRTL-5 thyroid cells. Abnormalities of hsp-90 phosphorylation may be a
      mediator in the development of thyroid disease.

PMID- 16910875
TI  - Experimental confirmation by Sir Victor Horsley of the relationship between
      thyroid gland dysfunction and myxedema.
AB  - Whereas Sir Victor Horsley is well known for his many contributions to
      neurosurgery, this is not the case for his treatments for both myxedema and
      cretinism. Horsley's research on thyroid physiology was concentrated in the years
      1884-1890, while he was director of the Brown Institute for Animals. Based upon
      experimentation with dogs and monkeys as well as some human patients, Horsley
      demonstrated conclusively that removal of the thyroid gland produced tremors,
      rigidity, and paralysis, which he attributed to changes in lower motor centers.
      Furthermore, the development of imbecility suggested that thyroid excision
      produced deficits in higher cortical functioning. Horsley showed that it was
      possible to alleviate temporarily some of the psychological and physiological
      symptoms of both myxedema and cretinism using transplanted thyroid tissue.
      Several of Horsley's students, most notably George Murray, continued and extended
      his work by examining other ways in which myxedema and cretinism could be treated
      (e.g., by injecting an extract of thyroid tissue).

PMID- 16910876
TI  - Low-energy interstitial laser photocoagulation for treatment of nonfunctioning
      thyroid nodules: therapeutic outcome in relation to pretreatment and treatment
      parameters.
AB  - OBJECTIVE: Interstitial laser photocoagulation (ILP) is a recently proposed
      therapeutic procedure for the ablation of benign thyroid nodules, which has
      already proven to be safe and effective. However, results supporting the routine
      use of ILP are still limited. DESIGN: The aim of the study was to evaluate the
      efficacy and safety of ILP treatment in benign nonfunctioning thyroid nodules and
      to establish whether the therapeutic outcome may be predicted by any clinical
      parameter at baseline. Twenty-three patients with either a solitary nodule or a
      dominant nodule within a multinodular goiter underwent ILP and were evaluated 1
      and 3 months later. In order to assess the efficacy of low-energy ILP, the
      procedure was performed with an output power of 3 W, delivering a mean energy of
      33.4 +/- 12.7 Joule/mL of nodule volume, which is much lower than previously
      reported. MAIN OUTCOME: Nodule volume significantly decreased after ILP as
      assessed after 1 and 3 months (analysis of variance; F = 5.37; p = 0.007).
      Patients with multinodular goiter showed a greater reduction at 3 months compared
      with patients bearing a solitary thyroid nodule (38.6 +/- 5.3 vs. 30.9 +/- 6.5%;
      p < 0.01). Age, sex, ultrasound pattern (isoechogenous/hypoechogenous),
      pretreatment volume, number of ILP treatments, and total energy delivered did not
      show any significant correlation with treatment outcome. CONCLUSIONS: Our results
      demonstrate that ILP can produce a significant reduction of thyroid nodule volume
      even when a much lower energy than previously reported is delivered. ILP
      constitutes a minimally invasive technique, which can be carried out on an
      outpatient basis and could represent a valid nonsurgical alternative for thyroid
      nodule management. Dominant nodules within a multinodular goiter appear to be
      more responsive to ILP compared with solitary thyroid nodules.

PMID- 16910877
TI  - The trapping-only nodules of the thyroid gland: prevalence study.
AB  - The aim of this study was to determine the prevalence of trapping-only nodules of
      the thyroid gland. The study was prospectively performed in patients bearing hot
      or warm thyroid nodules at pertechnetate scan in the presence of circulating
      thyrotropin (TSH) within the normal range. The study was restricted to these
      patients because nodules that suppress TSH are certainly autonomous. In 140
      patients showing hot or warm nodules at 30-minute pertechnetate scintigraphy, and
      normal TSH levels, radioiodine scintigraphy was performed at 24 hours. The
      trapping-only pattern, i.e., the presence of a cold nodule in late radioiodine
      scintigraphy was observed in seven patients (5%). Five had benign thyroid
      nodules, one follicular carcinoma, and one extrathyroid metastases of papillary
      follicular carcinoma. Despite controversy on this issue, trapping-only nodules of
      thyroid should be searched because they have risk of malignancy and must be
      differentiated from autonomous adenomas at the compensated stage. The search may
      be limited to patients with normal serum TSH.

PMID- 16910878
TI  - Effect of ultrasound-guided interstitial laser photocoagulation on benign
      solitary solid cold thyroid nodules: one versus three treatments.
AB  - OBJECTIVE: Interstitial laser photocoagulation (ILP) is a safe and effective
      procedure when inducing thyroid nodule necrosis. In this prospective randomized
      study, we evaluated a possible dose-response relationship as well as patient
      satisfaction. DESIGN: Thirty euthyroid outpatients with a cytologically benign
      solitary solid and scintigraphically cold thyroid nodule causing local discomfort
      were assigned to one session of ILP (ILP-1) (n = 15) or three monthly ILP
      sessions (ILP-3) (n = 15) and followed for 6 months. ILP was performed under
      continuous ultrasound (US)--guidance and with an output power of 2.5-3.5 W.
      Thyroid nodule volume was assessed by US. Pressure and cosmetic complaints were
      evaluated on a visual analogue scale. MAIN OUTCOME: In the ILP- 1 group, thyroid
      nodule volume decreased from 10.1 +/- 4.3 mL (mean +/- standard deviation [SD])
      to 5.7 +/- 3.2 mL (p = 0.0004), and in the ILP-3 group from 10.8 +/- 5.5 mL to
      4.6 +/- 3.0 mL (p = 0.0005) during follow-up. The overall mean difference between
      the two groups was 13%, corresponding to an improved mean thyroid nodule volume
      reduction of 30% (p = 0.03). In both groups subjective symptoms were
      significantly reduced, and without difference between the two groups (p = 0.7).
      No major side effects were seen in either group. CONCLUSION: As a nonsurgical
      therapeutic option, ILP-1 approximately halves thyroid nodule volume with
      concomitant symptom relief. There is little incremental effect of additional ILP
      treatment, which should be limited to patients with large nodules or limited
      nodule reduction after the first treatment.

PMID- 16910879
TI  - Goiter prevalence and urinary iodine concentration in Slovenian adolescents.
AB  - CONTEXT: Slovenian school-age children are, as are more than half of European
      school-age children, still considered to be iodine deficient. In 1999,
      supplementation of salt was increased from 10 to 25 mg of KI/kg of salt.
      OBJECTIVE: The objective of our study was to determine the success of this
      intervention. DESIGN AND PATIENTS: Twelve hundred sixty-four girls (mean age +/-
      SD: 15.7 +/- 0.6 years) and 1200 boys (15.8 +/- 0.8 years) representing 10% of
      all 15-year-old Slovenian adolescents were studied. Thyroid size was estimated by
      clinical examination in all subjects and by ultrasound when enlarged thyroid was
      suspected. Thyroid volume was also determined by ultrasound in 108 random iodine
      sufficient adolescents. In addition, urinary iodine concentration was determined
      in all subjects. RESULTS: Enlarged thyroid was determined by clinical examination
      and ultrasound in 0.9% of all subjects. In randomly selected iodine-sufficient
      subjects, enlarged thyroid was determined in 4.6%. Median urinary iodine
      concentration for the population was 140 microg/L. In all regions it was greater
      than or equal to 100 microg/L. Values less than 50 microg/L were determined in
      2.5% of all subjects. CONCLUSIONS: Slovenian adolescents are iodine sufficient
      and the prevalence of goiter is low, indicating that increased KI supplementation
      of salt in 1999 was successful.

PMID- 16910880
TI  - Prognostic significance of cytologic features in fine-needle aspiration cytology
      samples of papillary thyroid carcinoma: preliminary report.
AB  - BACKGROUND: The influence of clinicopathologic features on prognosis of papillary
      thyroid cancer has been examined. However, the relationship between cytologic
      features obtained by fine-needle aspiration (FNA) and prognosis has been
      minimally studied. METHODS: We retrospectively studied 85 patients with usual
      type papillary thyroid cancer diagnosed by FNA who underwent total or near-total
      thyroidectomy, had disease confirmed by pathological study, and were followed for
      more than 10 years except for one patient with metastasis at diagnosis. Cytologic
      features of FNA and recurrence of cancer were examined statistically. RESULTS:
      Four cytologic features were significantly related to recurrence: bigger nuclei,
      more irregularly shaped nuclei, nuclear atypia, and simultaneous presence of
      lighter staining nuclei and apparent nucleoli. A prognostic score of 1 (light
      nuclei and apparent nucleoli) plus 1.5 (irregularly shaped nuclei away from
      fibrous cord) plus 1 (high nucleus-to-cytoplasm ratio) plus 1 (nuclear atypia)
      was generated statistically. Sensitivity and specificity using a cut point of 2.5
      in predicting outcome were 83.33% and 77.55%, respectively. CONCLUSIONS:
      Cytologic features of FNA samples have prognostic significance. If the prognostic
      score of cytologic features is high, a more radical surgical procedure and
      aggressive treatment plan should be considered.

PMID- 16910881
TI  - Validation of a five-tier cytodiagnostic system for thyroid fine needle
      aspiration biopsies using cytohistologic correlation.
AB  - OBJECTIVE: Approximately 70-80% of thyroid fine needle aspiration biopsies (FNAB)
      can distinguish benign from malignant thyroid nodules. However, much interpretive
      diagnostic difficulty arises with the remaining 20-30% of cases. These
      problematic thyroid aspirations have been placed in various diagnostic
      categories, which collectively have led to confusion and a negative impact on the
      clinical management of patients with thyroid nodules. We present our experience
      using a five-tier system, including the diagnostic terminology: benign,
      indeterminate, suspicious, malignant, and unsatisfactory. DESIGN: Thyroid FNABs
      were diagnosed using a five-tier system from 200 consecutive patients and the
      subsequent surgical excisions were correlated. MAIN OUTCOME: Overall, there was
      an excellent association between the five diagnostic categories and predicting
      benign versus neoplastic thyroid nodules (LR = 96.06, X(2) = 76.49, and phi =
      0.618, df = 4, p < 0.0001). A negative cytologic diagnosis carries a negative
      predictive value of 92%, while an indeterminate, suspicious, and malignant
      cytologic diagnosis carries a positive predictive value of 50, 71, and 100%
      respectively. The estimated sensitivity for an indeterminate, suspicious, or
      malignant cytologic diagnosis varied from 70 to 89%, while the specificity
      increased from 57 to 92 to 100%, respectively. CONCLUSIONS: The data presented
      shows that the five diagnostic categories of thyroid FNAB are excellent at
      distinguishing benign from neoplastic thyroid nodules. Both the indeterminate and
      suspicious categories, while not statistically different from each other in
      predicting benign from neoplasia, are statistically different from obviously
      benign and obviously malignant categories. These results support the need for an
      indeterminate and/or suspicious category.

PMID- 16910882
TI  - Preoperative selective venous sampling for nonlocalizing parathyroid adenomas.
AB  - INTRODUCTION: Preoperative parathyroid adenoma localization allows for a
      minimally invasive surgical approach. Current methods used for adenoma
      localization include ultrasound, sestamibi scan, and occasionally magnetic
      resonance imaging (MRI). In cases in which an adenoma is not localized after a
      radiologic work-up, the surgeon must perform a four-gland exploration.
      Preoperative selective venous sampling (SVS) has been described as a safe and
      clinically effective method to localize a parathyroid adenoma after failed
      exploration. The purpose of this study was to evaluate the efficacy of SVS as a
      primary localization technique in cases where conventional localization
      techniques have failed. MATERIALS AND METHODS: Fourteen patients with
      nonlocalizing parathyroid adenomas after ultrasonography, sestamibi scanning, and
      MRI were retrospectively reviewed. Eight patients underwent SVS prior to surgery
      and six patients underwent a four-gland neck exploration without preoperative
      SVS. The two groups were assessed for accuracy of the SVS in localizing the
      adenoma, operative time, length of hospitalization, and complications. RESULTS:
      All of the patients in the study underwent successful uncomplicated surgical
      parathyroidectomy. The SVS proved accurate in preoperatively localizing the
      adenoma in 7 of 8 patients and allowed for a minimally invasive approach in 87%
      of patients. The mean operative time was 33 minutes for the SVS group and 67
      minutes in the non-SVS group. None of the patients in either group experienced
      procedural complications. CONCLUSION: This study suggests that preoperative SVS
      may represent a safe and effective method of preoperatively localizing the
      nonlocalized parathyroid adenoma. In cases where conventional radiologic
      techniques fail to localize an adenoma, SVS may obviate the need for a four-gland
      exploration.

PMID- 16910883
TI  - Graves' disease and coexisting struma ovarii: struma expression of thyrotropin
      receptors and the presence of thyrotropin receptor stimulating antibodies.
AB  - Struma ovarii is a rare cause of hyperthyroidism and particularly rare in
      patients with coexisting Graves' disease. We describe a 28-year-old female who
      presented with symptoms and signs of hyperthyroidism (free thyroxine [FT(4)] 39
      pmol/L, thyrotropin [TSH] < 0.05 mU/L) and associated ophthalmopathy, consistent
      with Graves' disease. The patient relapsed twice: once after initial successful
      management with carbimazole and subsequently after subtotal thyroidectomy.
      Radioisotope scanning showed focal uptake bilaterally in the neck and believing
      this was the source of thyroid hormone excess, carbimazole was restarted. A left
      ovarian mass was found on ultrasound during the investigation of unrelated
      nephrotic syndrome resulting from focal segmental glomerulosclerosis. A 555-g
      struma ovarii was removed surgically. Hypothyroidism developed postoperatively
      (FT(4) 9.7 pmol/L, TSH 36 mU/L). Circulating TSH receptor stimulating antibodies
      were positive and immunohistochemical studies confirm the presence of TSH
      receptors on the struma ovarii. The demonstration of TSH receptors on the struma
      ovarii increases previous speculation that struma ovarii growth and function may
      be augmented by the circulating TSH receptor stimulating antibodies of Graves'
      disease.

PMID- 16910884
TI  - Huge intrathyroidal hematoma causing airway obstruction: a multidisciplinary
      challenge.
AB  - Thyroid hemorrhage is a relatively frequent event that in most cases causes pain
      and discomfort only, while rarely can cause significant neck swelling. Even more
      rarely, however, extensive thyroid hemorrhage can result in a rapidly expanding
      hematoma with airway compromise. We report a case of a rapidly expanding thyroid
      hemorrhage that occurred secondary to oral anticoagulation therapy in an 80-year
      old patient with a previously existing goiter. The patient presented with acute
      onset of neck pain, dysphagia, and respiratory distress caused by tracheal
      compression from the thyroid mass. Computed tomography demonstrated a 6 x 9 x 10
      cm mass consistent with an intrathyroidal hematoma projecting into the anterior
      mediastinum and displacing the trachea to the left. Rapid reversal of the
      coagulopathy was achieved with fresh frozen plasma and vitamin K. Consequently,
      the patient was managed conservatively with close observation, antibiotics, and
      steroids because no progression of airway compromise was manifested. Although the
      diagnosis can be easily established in these patients, no management guidelines
      of this condition exist. The potential of rapid airway compromise and the risk
      for exacerbation of bleeding in the light of significant elevation in the
      international normalized ratio (INR), make any airway management decisions very
      difficult. The importance of managing the airway and the haemostatic problem with
      the help of a multidisciplinary team is discussed.

PMID- 16910885
TI  - Capecitabine therapy for refractory metastatic thyroid carcinoma: a case series.
AB  - OBJECTIVE: There are few effective therapies for metastatic medullary (MTC) or
      radioiodine-resistant follicular thyroid carcinomas (FTC). We report a single
      institution's experience with capecitabine, a thymidylate synthase (TS)
      inhibitor, in the treatment of MTC and FTC. DESIGN: We retrospectively analyzed
      five cases of metastatic thyroid carcinoma, three MTCs and two radioiodine
      resistant FTCs, treated with capecitabine alone or in combination with other
      chemotherapeutics. Patients were selected for treatment based on low tumor TS
      immunohistochemical staining (< or =5%). Staining for thymidylate phosphorylase
      (TP) and dihydropyrimidine dehydrogenase (DPD) was also performed. Therapeutic
      response was assessed by imaging studies and serum tumor markers: calcitonin and
      carcinoembryonic antigen (MTC), and thyroglobulin (FTC). MAIN OUTCOME: Two of
      three patients with MTC had stable disease or disease regression on capecitabine.
      One of these patients had a 90% reduction in calcitonin and stabilization by
      imaging that lasted 4 years. Both patients with FTC initially had stable disease
      on capecitabine. One patient, who was treated with capecitabine in combination
      first with doxorubicin and then etoposide, had an initial decrease in tumor
      burden, followed by stable disease for 2.8 years. The second patient had stable
      disease, but capecitabine was discontinued after 11 months because of hand/foot
      syndrome. CONCLUSIONS: This series demonstrates promising results for the use of
      capecitabine in treatment of MTC and radioiodine-resistant FTC, for which there
      is a limited repertoire of therapeutic agents. Larger studies are needed to
      confirm these findings and to establish the role of fluoropyramidine metabolism
      markers in predicting response.

PMID- 16910886
TI  - Black thyroid syndrome.

PMID- 16910887
TI  - Reversible severe tricuspid regurgitation with right heart failure associated
      with thyrotoxicosis.

PMID- 16910888
TI  - Elephantiasic pretibial myxedema and cutis verticis gyrata caused by Graves'
      disease.

PMID- 16910889
TI  - Stunning and I-123 use for diagnostic whole body scanning.

PMID- 16910891
TI  - Fine needle aspiration cytology of thyroid nodule.

PMID- 16910899
TI  - Abstracts from the Women's Health 2nd NIH Interdisciplinary Research Symposium,
      October 20, 2005.

PMID- 16910901
TI  - Improving women's health during internatal periods: developing an evidenced-based
      approach to addressing maternal depression in pediatric settings.
AB  - The internatal period, the time between births of successive children, has become
      a focal point for risk assessment and health promotion in women's healthcare.
      This period represents a time when women are at high risk for a depressive
      disorder. The pediatric venue offers a unique opportunity for the identification
      and management of depression in the internatal period, as mothers who do not
      attend their own medical appointments are likely to accompany their child to
      pediatric visits. This paper discusses the role pediatric providers can undertake
      to improve women's health in the internatal period through the detection and
      management of maternal depression at well-child visits. Successful models of the
      management of depression in other primary care settings are explored for their
      potential for implementation in the pediatric venue. A specific model developed
      and implemented as part of a 3-year project is presented to highlight the
      feasibility of an evidenced-based approach to the management of maternal
      depression in the pediatric setting. We present evidence demonstrating that
      pediatric providers can successfully identify postpartum women with depression,
      monitor symptoms and treatment adherence, and communicate results to a woman's
      healthcare provider. Yet more investigation is needed to create preventive
      interventions for maternal depression that integrate evidenced-based practice
      standards for the treatment of depression in primary care venues into pediatric
      settings. Future programs and policies targeting maternal depression in the
      pediatric environment should address patient mental health literacy and stigma,
      the training and education of pediatric providers, and issues of privacy and
      reimbursement.

PMID- 16910902
TI  - Toward optimal health: Leon J. Thal, M.D. discusses the latest in Alzheimer's
      disease in women. Interview by Jodi R. Godfrey.

PMID- 16910903
TI  - Ethnic variation in risk for osteoporosis among women: a review of biological and
      behavioral factors.
AB  - Most studies of risk factors for osteoporosis and nontraumatic fracture involve
      white women, although more research is being geared toward bone health among
      various ethnic groups. The purpose of this review is to provide an overview of
      health disparity in osteoporosis, including assessment of bone mineral density
      (BMD), bone health screening, lifestyle risk factors, and treatment involving
      white, black, Hispanic, Asian, and Native American women. This review summarizes
      evidence that white, Asian, Hispanic, and Native American women are more at risk
      for osteoporosis than black women. These conclusions are supported by the
      disparity in BMD between white and black women, although the reason for this
      biological difference is not well characterized. Additional research is needed to
      determine if there is a significant difference in BMD among Hispanic, Asian, and
      Native American women independent of body weight and size. Similarly, there is
      also disparity in fracture rates, with the causes presumed to be multifactorial.
      Calcium intake is lower than recommended in all females at all ages; however, it
      is much lower in black and Native American women and highest in white and
      Hispanic women. Black women also have a lower vitamin D status than white women,
      with mean vitamin D status of Hispanic American women lying between that of black
      and white women. Similarly, although white women are more active than black and
      Hispanic women at all ages, data are lacking about physical activity habits of
      women of other ethnic backgrounds and how this impacts bone health. Finally,
      screening protocols for women of various ethnicities and effectiveness of
      treatments are not well established and remain a priority in women's health.

PMID- 16910904
TI  - Pregnancy and obesity: a review and agenda for future research.
AB  - At present, more than 60% of American women of childbearing age are either
      overweight or obese. As the obesity epidemic in the United States and many other
      countries continues to grow unchecked, there is greater interest in the
      relationship between obesity and other major health issues. This paper reviews
      the literature on the relationship between obesity and pregnancy. We begin with a
      discussion of the relationship between excess body weight and fertility and then
      turn to the relationship between maternal body weight and pregnancy-related
      complications. The role of pregnancy as a possible risk factor for the
      development of obesity is noted. The studies investigating the efficacy of
      behavioral interventions to control excessive weight gain during pregnancy or
      help women lose weight after childbirth are then reviewed. The paper concludes
      with an agenda for future research examining the relationship between obesity and
      pregnancy.

PMID- 16910905
TI  - Recent changes in cardiovascular risk factors among women and men.
AB  - BACKGROUND: The purpose of this study was to examine change over the 1990s in the
      proportion of men and women with measured high-risk values of cardiovascular risk
      factors. METHODS: Change in the prevalence of high-risk conditions based on
      clinical cutoffs for 10 cardiovascular risk factors was assessed in respondents
      aged > or =40 from the nationally representative, cross-sectional National Health
      and Nutrition Examination Surveys (NHANES) III (1988-1994) and IV (1999-2002).
      RESULTS: Both sexes experienced a reduction in the prevalence of high-risk levels
      of cholesterol (total, high-density lipoprotein [HDL], and low-density
      lipoprotein [LDL]) and high homocysteine and an increase in obesity and high C
      reactive protein (CRP). Changes in the prevalence of high total cholesterol and
      high CRP were more pronounced among women. The percentage of women with high
      diastolic and systolic blood pressure increased, whereas this percentage
      decreased among men. During the same time, there was an increase in undiagnosed
      high blood pressure and in the use of antihypertensive medications without
      achieving adequate blood pressure control among women. Both sexes increased their
      use of cholesterol-lowering medication. These changes in diagnosis rates and
      medication usage did not explain the trends in the prevalence of high-risk blood
      pressure or high-risk cholesterol, although the larger increase in high CRP among
      women is related to increased use of postmenopausal hormone therapy over the
      1990s. CONCLUSIONS: We found mixed trends in cardiovascular risk factors for both
      women and men; some improved and some deteriorated. Changes in medication use and
      obesity did not explain these trends.

PMID- 16910907
TI  - Association of breastfeeding with maternal depressive symptoms.
AB  - PURPOSE: To identify risk factors for lack of breastfeeding initiation and
      duration of <1 month among a racially diverse cohort of women. In particular, our
      interest was to examine depressive symptoms during pregnancy as a potential risk
      factor for not initiating or continuing breastfeeding. METHODS: Survey and
      medical record data from a cohort of pregnant women from the San Francisco Bay
      area who delivered a singleton infant (n = 1448) were analyzed to examine lack of
      breastfeeding initiation and duration of <1 month. RESULTS: In this study, 5.6%
      of women did not initiate breastfeeding, and 11.1% of women who initiated
      breastfeeding had a duration of breastfeeding of <1 month. There were no racial
      or ethnic differences in initiation of breastfeeding after adjusting for
      demographic and clinical characteristics. At 1 month postpartum, African American
      women were more likely than white women to have a duration of breastfeeding
      lasting <1 month. Depressive symptoms during or prior to pregnancy had no effect
      on initiation of breastfeeding even when symptoms were persistent. Women with
      persistent depressive symptoms (symptoms at two time points, including one prior
      to delivery) were more likely to have breastfeeding duration of <1 month (odds
      ratio [OR] 1.77, 95% confidence interval [95% CI] 1.10-2.86), whereas depressive
      symptoms at a single time point were not associated with breastfeeding duration
      of <1 month. CONCLUSIONS: Addressing depressive symptoms experienced by women
      both during and after pregnancy may improve the duration of breastfeeding.

PMID- 16910906
TI  - Older women's attitudes, behavior, and communication about sex and HIV: a
      community-based study.
AB  - OBJECTIVES: To examine the effects of race and marriage on the sexual attitudes,
      behavior, and patient-physician communication about sexuality and HIV/AIDS among
      older women. METHODS: This was a cross-sectional survey of 55 community-residing
      women aged 58-93. RESULTS: 57% of respondents had engaged in sexual activity
      since the 60th birthday. Nearly 60% of single women who had been sexually active
      in the previous 10 years reported that they had not used a condom; 21% of women
      with a current sexual partner agreed that condom use is not necessary "if you can
      no longer get pregnant." African American women were significantly more likely to
      report making changes in their sexual behavior due to HIV (53% vs. 19% white, p =
      0.02). Married and African American women were more likely to discuss sex with a
      physician (80% vs. 47%; p = 0.03 and 75% vs. 46%, p = 0.05, respectively).
      African Americans were more likely to have had a physician initiate such a
      discussion (69% vs. 38%, p = 0.04). CONCLUSIONS: Older women in this sample were
      sexually active, engaged in potentially risky sexual behavior, and believed that
      physicians should address issues of sexuality. Older African American women were
      significantly more likely than white women to report HIV-related changes in their
      behavior and to discuss sex with a physician. This community-based study
      corroborates clinical research and suggests both a gap and a disparity in older
      women's dialogue with physicians. It also indicates the need for more broadly
      generalizable data on issues pertinent to older women's sexual health.

PMID- 16910908
TI  - Number of children and risk of metabolic syndrome in women.
AB  - BACKGROUND: In the United States, there is a high prevalence of metabolic
      syndrome, as defined by The Third Report of the National Cholesterol Education
      Program Expert Panel on Detection, Evaluation, and Treatment of High Blood
      Cholesterol in Adults (ATP III). The relationship between reproductive factors
      and metabolic syndrome in women is unknown. METHODS: We examined the association
      of number of children and breastfeeding history with metabolic syndrome risk
      among women. We used nationally representative data from the Third National
      Health and Nutrition Examination Survey (NHANES III). A total of 4699 (age > or =
      20) nonpregnant women were included in this report. Metabolic syndrome was
      defined according to ATP III. RESULTS: Overall, 22.6% of women were determined to
      have metabolic syndrome. The rate of metabolic syndrome was significantly higher
      with increasing numbers of children, demonstrating a dose-response relationship
      (p < 0.0001). After controlling for age, race/ethnicity, income, education, and
      other sociodemographic, reproductive, and behavioral risk factors, the odds of
      metabolic syndrome increased 13% (95% CI, 6%-20%) with each additional child. In
      a similarly controlled analysis in parous women, the odds of metabolic syndrome
      decreased 22% (95% CI, 1%-39%) in women with a history of breastfeeding for >1
      month. However, both effects were no longer significant after inclusion of body
      mass index (BMI) categories. CONCLUSIONS: In a national sample of women,
      increasing number of children was associated with higher rates of metabolic
      syndrome, and history of breastfeeding was associated with decreased rates of
      metabolic syndrome. The strength of these relationships was decreased after
      additional adjustment for BMI, suggesting that weight or weight changes may be an
      important mediator of the effects of parity and breastfeeding on the risk of
      metabolic syndrome.

PMID- 16910909
TI  - Relationship between English language use and preferences for involvement in
      medical care among Hispanic women.
AB  - OBJECTIVE: To assess how English language use by Hispanic women affects their
      preferences for participating in decision making and information seeking
      regarding medical care. METHODS: The study included 235 Hispanic women aged 35-61
      years participating in a larger multicenter study, the Ethnicity, Needs, and
      Decisions of Women (ENDOW) Project. Participants were recruited from community
      settings and primary care public health clinics. Bilingual (English and Spanish
      speaking) interviewers asked participants questions about demographic
      characteristics, health status, reproductive history, menopausal status, access
      to healthcare, experience with hormone replacement therapy (HRT) and
      hysterectomy, outcome expectations about HRT and hysterectomy, medical decision
      making, and social support. Using univariate and multivariate analyses, we
      assessed the relationships between the participants' preferences for
      participating in decision making and information seeking, their language use, and
      other covariates of interest. RESULTS: Overall, the participants expressed a
      strong desire for information about and participating in medical decisions.
      However, they expressed a lower preference for participating in decisions related
      to use of HRT compared with the desire for engaging in decision involving
      invasive medical procedures (hysterectomy and cholecystectomy) and high blood
      pressure management. Increased use of English language was significantly
      associated with preferences for participating in medical care decision making, in
      general (p < 0.001), and with information seeking (p = 0.044). Decreased use of
      English language was associated with a lower desire for participating in medical
      care decision making. CONCLUSIONS: Increased use of English language may
      influence Hispanic women's preferences for participating in medical decisions and
      their information-seeking behavior.

PMID- 16910910
TI  - Female resistance to hypoxia: does it explain the sex difference in mortality
      rates?
AB  - There is currently no accepted explanation in the medical literature for the
      lower female total mortality rate in infancy, childhood and adulthood. We review
      the pediatric mortality data provided by Centers for Disease Control and
      Prevention (CDC) and the World Health Organization (WHO) and show that for causes
      of respiratory infant death that are apparently independent of gender (e.g.,
      suffocation from inhalation of food or other object), there is a consistently one
      third lower rate of mortality in the female than in the male. This one-third
      lower mortality for causes of death with a respiratory terminal event is
      hypothesized to be due to an X-linked dominant allele that occurs with frequency
      1/3. It appears as if a second X chromosome provides the one-third extra
      probability of protection afforded for an XX female compared with an XY male. It
      is suggested that the allele's function is unmasked during transient periods of
      cerebral anoxia, requiring a mechanism for anaerobic oxidation to prevent the
      death of respiratory control neurons in the brain stem. Examples of the female
      one-third extra chance of resistance to hypoxia are given for causes of death in
      infancy, such as infant respiratory distress syndrome (IRDS) and sudden infant
      death syndrome (SIDS), and for causes of suffocation in childhood and
      asphyxiation in adulthood. DNA testing of the X chromosome of probands from
      causes of respiratory death, such as SIDS and IRDS, where there is a one-third
      lower female than male death rate, is a future direction that can verify the
      existence of the proposed allele.

PMID- 16910913
TI  - Therapeutic doses of glucocorticoids: implications for oral medicine.
AB  - Glucocorticoids can cause adverse systemic side-effects ranging from iatrogenic
      Cushing's syndrome during treatment, to hypothalamic-pituitary-adrenal axis
      suppression and clinically significant adrenal insufficiency when the agents are
      discontinued. While the oral route of administration is most often implicated, it
      is now becoming more apparent that inhaled and topical administration also can
      cause these effects. Given the high therapeutic value of glucocorticoids, the
      ability to prescribe these agents while maintaining a low risk-to-benefit ratio
      for patients is critical. The aim of this review is to provide oral healthcare
      practitioners with a practical guide to commonly used glucocorticoids, their
      adverse effects, and perioperative use.

PMID- 16910914
TI  - Cancer stem cells - new and potentially important targets for the therapy of oral
      squamous cell carcinoma.
AB  - There is increasing evidence that the growth and spread of cancers is driven by a
      small subpopulation of cancer stem cells (CSCs) - the only cells that are capable
      of long-term self-renewal and generation of the phenotypically diverse tumour
      cell population. Current failure of cancer therapies may be due to their lesser
      effect on potentially quiescent CSCs which remain vital and retain their full
      capacity to repopulate the tumour. Treatment strategies for the elimination of
      cancer therefore need to consider the consequences of the presence of CSCs.
      However, the development of new CSC-targeted strategies is currently hindered by
      the lack of reliable markers for the identification of CSCs and the poor
      understanding of their behaviour and fate determinants. Recent studies of cell
      lines derived from oral squamous cell carcinoma (OSCC) indicate the presence of
      subpopulations of cells with phenotypic and behavioural characteristics
      corresponding to both normal epithelial stem cells and to cells capable of
      initiating tumours in vivo. The present review discusses the relevance to OSCC of
      current CSC concepts, the state of various methods for CSC identification,
      characterization and isolation (clonal functional assay, cell sorting based on
      surface markers or uptake of Hoechst dye), and possible new approaches to
      therapy.

PMID- 16910915
TI  - Differential regulation of IL-2 and IL-4 in patients with tobacco-related oral
      squamous cell carcinoma.
AB  - AIM: The aim of the study was to investigate the systemic immunity in terms of
      major lymphocyte subsets and the expression of IL-2 and IL-4 in T-cell subsets
      from peripheral blood of patients with tobacco-related intraoral squamous cell
      carcinoma. METHODS: CD3+, CD4+ and CD8+ T-cell subsets and CD16+ CD56+ natural
      killer cells, and intracellular cytokines in T-cell subsets were determined by
      two-colour flow cytometry and confocal microscopy. RESULTS: Oral cancer patients
      showed a significantly reduced (P < 0.001) CD3+ and CD4+ T-cell subsets with a
      lower CD4/CD8 ratio when compared with the normal controls. The frequency of CD3+
      IL-4+ and CD8+ IL-4+ T cells were significantly higher (P < 0.001) while CD4+ IL
      2+ were significantly lower (P < 0.02) in patients when compared with the normal
      controls. Late stage of the tumour was associated with reduced expression of IL-2
      in both CD4+ (P < 0.05) and CD8+ (P < 0.03) subsets. CONCLUSIONS: The tobacco
      related intraoral squamous cell carcinoma seems to be associated with multiple
      systemic immune defects particularly, an impaired CD3+ and CD4+ T cells in the
      peripheral blood as well as a differential regulation of IL-2 and IL-4 in CD4+
      and CD8+ T-cell subsets. The cytokine response in these patients seems to be
      skewed from protective Th1 to immunosuppressive Th2 type. Thus these patients
      could be ideal candidate for immunomodulation therapy.

PMID- 16910916
TI  - Oral lichen planus: a retrospective study of 690 British patients.
AB  - OBJECTIVE: This is the largest UK patient group with oral lichen planus (OLP) to
      be studied in terms of the demographic and clinical characteristics. MATERIALS
      AND METHODS: Data were taken from the medical records of 690 consecutive patients
      referred to Oral Medicine subsequently found to have clinical, and usually
      histopathological confirmatory features of OLP. Over two-thirds (68.7%) of the
      patients were Caucasians. RESULTS: Eighty-two per cent of the patients had been
      referred to a specialist Oral Medicine service by general dental practitioners,
      62% of the patients being referred as a consequence of oral mucosal and/or
      gingival pain. Reticular OLP was the most common intra-oral presentation, but 60%
      of such lesions were accompanied by other clinical types of OLP. 95% of lesions
      were bilateral. About 13% of patients reported symptoms or signs, or had a known
      history of lichen planus or possible lichen planus affecting non-oral epithelia.
      In only 13% of patients did all signs and symptoms of OLP resolve within 12-246
      months (median 35 months). A malignant transformation rate of 1.9% was observed
      in the present group. CONCLUSIONS: Oral lichen planus in UK persons almost always
      gives rise to bilateral reticular OLP, rarely resolves spontaneously, and has a
      low rate of malignant transformation.

PMID- 16910917
TI  - Microvessel density and vascular endothelial growth factor expression in sinus
      augmentation using Bio-Oss.
AB  - AIM: The aim of this study was to evaluate microvessel density (MVD) and vascular
      endothelial growth factor (VEGF) expression in sinus augmentation with Bio-Oss.
      METHODS: Twenty patients participated in this study. The sinuses were filled with
      100% Bio-Oss. Implants were inserted after 3 months in group A, and 6 months in
      group B. A trephine was used to harvest bone cores. As control, the pre-existing
      subantral bone was used. RESULTS: The mean MVD in control bone was 23.6 +/- 1.8.
      In the sites augmented with Bio-Oss, at 3 months, the MVD was 23.3 +/- 2.1, while
      in the sites retrieved at 6 months the MVD was 29.5 +/- 2.4. The difference in
      MVD between the control bone and group A was not statistically significant. The
      difference between the control bone and group B was statistically significant (P
      < 0.05). The statistical analysis showed that the difference in MVD between group
      A and group B was statistically significant (P < 0.05). CONCLUSIONS: Bio-Oss
      seemed to induce an increase in MVD that reached a higher value after 6 months.
      The percentage of vessels positive to VEGF was higher in group A than in group B.
      Our data also showed a higher percentage of vessel and stromal cells positive to
      VEGF and higher MVD values in areas where there was newly formed bone compared
      with areas where maturation processes were occuring, and this fact could point to
      a close spatial relationship between angiogenesis and osteogenesis.

PMID- 16910918
TI  - Sialadenitis following radioiodine therapy - a new diagnostic and treatment
      modality.
AB  - OBJECTIVES: To explore the usage of salivary gland endoscope technique as a
      diagnostic tool as well as a novel treatment modality for sialadenitis following
      radioiodine therapy. SUBJECTS AND METHODS: Fifteen patients suffering from
      sialadenitis of the major salivary glands after I131 therapy for thyroid
      carcinoma underwent a single procedure of sialoendoscopy under local anesthesia.
      RESULTS: All the patients were free of sialadenitis after one sialoendoscopy
      procedure with no complications accompanied. CONCLUSIONS: Sialoendoscopy is an
      efficient technique with low morbidity as well as a relatively simple surgical
      method for diagnosing and treating sialadenitis induced by radioiodine therapy
      for thyroid cancer patients.

PMID- 16910919
TI  - Evaluation of palatal saliva flow rate and oral manifestations in patients with
      Sjogren's syndrome.
AB  - OBJECTIVE: The purpose of this study was to describe the oral properties of
      Sjogren's syndrome (SS), including the determination of palatal saliva (PS) flow
      rate. SUBJECTS AND METHODS: Forty-nine SS patients and 43 healthy controls
      participated. Subjective symptoms were recorded and clinical assessments of the
      oral mucosal, dental and periodontal status were made. Unstimulated whole saliva
      (WS) and PS flow rates, the number of decayed, missing and filled teeth (DMF-T
      number), the gingival bleeding index (GBI) and the periodontal probing depth
      (PPD) were determined. RESULTS: Despite the decrease in the flow rate of WS in SS
      patients, PS was not different from those of the controls (1.57 +/- 1.02 and 1.35
      +/- 2.5 microl cm(-2) min(-1), respectively). GBI (20.0% vs. 10.5%,
      respectively), DMF-T (27.1 +/- 6.12 vs. 23.0 +/- 6.99, respectively) and PPD
      (2.28 +/- 1.09 mm vs. 1.82 +/- 0.73 mm, respectively) were higher in SS compared
      with the controls (P < 0.05). DMF-T and PPD showed a positive correlation with
      anti-SSA and/or anti-SSB antibody positivity in the serum (P < 0.05).
      CONCLUSIONS: Data of the present study suggest that the subjective feeling of
      xerostomia in SS patients is the result of a decrease in the volume of the whole
      saliva, and not of the viscous PS. Correlation of DMF-T and PPD with autoantibody
      positivity reveals that the oral health status of SS patients may be associated
      with the general autoimmune process.

PMID- 16910920
TI  - Oral cancer: experiences and diagnostic abilities elicited by dentists in North
      western Spain.
AB  - BACKGROUND: Opinions, knowledge, behaviours and attitudes of general dental
      practitioners on oral cancer prevention and detection have been reported from
      many countries. However, experiences and skills of oral cancer detection have not
      been evaluated systematically. OBJECTIVE: To obtain information on behaviours of
      screening and ability to correctly detect oral cancer and precancer among general
      dentists (GDP) in North-western Spain. SUBJECTS AND METHODS: Thirty-two randomly
      selected GDPs completed questionnaires and then classified 50 projected images of
      clinical lesions, into cancer, precancer or benign lesions. RESULTS: 87.5%
      reported conducting routine oral examinations, 84.4% provided routine advice to
      their subjects for risk modifications and 84.4% claimed to biopsy a suspected
      oral mucosal lesion that they detected in practice. In a quasi research setting
      using clinical slides, the sensitivity of visual diagnosis of a cancerous lesion
      was 61.4% and precancer 59.5%. The diagnostic accuracy reported here is lower
      than what is already reported by evaluation of published screening programmes by
      dentists. CONCLUSIONS: Our data from Spain suggest a need for improving the
      diagnostic ability of GDPs in the visual detection of oral cancer/precancer by
      strengthening continuing professional education.

PMID- 16910921
TI  - Chemokine receptor expression in HIV-positive persons with oropharyngeal
      candidiasis.
AB  - OBJECTIVE: In HIV+ persons with reduced CD4+ T cells, oropharyngeal candidiasis
      (OPC) is often associated with the accumulation of CD8+ T cells at the
      epithelial/lamina propria interface within the lesion together with increased
      tissue-associated cytokines and chemokines. Despite this reactivity, a
      dysfunction in the ability of the CD8+ cells to reach the organism at the outer
      epithelium is postulated. The purpose of this study was to examine chemokine
      receptors present in the OPC lesions for a potential role in susceptibility to
      infection. METHODS: Biopsies taken from buccal mucosa of HIV- persons, healthy
      mucosa of HIV+ OPC- persons, and OPC lesions were processed for protein
      immunohistochemical staining or RNA analysis by real-time PCR and Superarray.
      RESULTS: There was little change in expression of chemokine receptors at the
      protein or RNA level between OPC+ and OPC- tissue. At the protein level,
      increases occurred in OPC+ persons only if associated with CD8 cells. In the
      Superarray, of the 22 chemokine receptor mRNAs expressed, c. 90% remained
      unchanged (< 1.0-fold change) between HIV- and HIV+ tissue and between HIV+ OPC-
      and HIV+ OPC+ tissue. CONCLUSION: Tissue-associated chemokine receptor expression
      does not appear to contribute to the dysfunction in cellular migration associated
      with susceptibility to OPC.

PMID- 16910922
TI  - Herpes zoster in HIV infection with osteonecrosis of the jaw and tooth
      exfoliation.
AB  - BACKGROUND: Herpes zoster (HZ) infection of the trigeminal nerve is associated
      with complications such as postherpetic neuralgia, facial scarring, loss of
      hearing ability and conjunctivitis. Until 2005, postherpetic alveolar necrosis
      and spontaneous tooth exfoliation have been described in 20 cases unrelated to
      HIV infection. OBJECTIVE: The aim of this study was to describe HIV infection in
      patients (two women, two men, average age 30 years) who suffered from HZ attacks
      to their trigeminal nerves. MAIN OUTCOME MEASURES: None of the patients had
      received antiherpetic medications or antiretroviral therapy. HIV infection was
      only diagnosed after the development of HZ. Facial scarring with depigmentation
      and hyperesthesia (postherpetic neuralgia) was diagnosed in all four patients.
      Oral findings consisted of spontaneous loss of both maxillary or mandibular
      teeth. Osteonecrosis of varying extent was also found. Treatment consisted of
      extractions of teeth and administration of antibiotics and analgesics. Healing of
      alveolar wounds was unremarkable. CONCLUSION: Complications affecting the
      alveolar bone and teeth seem to be rare in HIV-infected patients.

PMID- 16910923
TI  - Hay-Wells syndrome (AEC): a case report.
AB  - We would like to present a case of the rare genetic skin disorder catalogued as
      AEC syndrome. This rare disorder was described in 1976 by Hay and Wells in seven
      individuals from four families, and it entails a complex polymalformative
      syndrome with an autosomal-dominant inheritance pattern and variable penetration.
      Descriptive explanation and facial and intraoral images of this rare disorder
      constituted the study design. The neonatal report outlines dysplastic phenotype,
      micrognathia, hypoplasia of the hard and soft palate, cleft palate, small nose,
      mammary hypoplasia with ectopic mammary nodules, hypoplastic external genitalia
      with clitoral hypertrophy, hypoplasia of the nails, a tendency towards
      dorsiflexion of the big toe on both feet, ankyloblepharon filiforme, low
      positioning of the auricles and faulty development of the left auricle, scaly
      exanthema with eritrodermatitis and hyperkeratosis, good lung ventilation, normal
      heart rhythm and normal neurological examination. Although only a few cases
      published are available, clinical variability is one of the hallmarks of AEC
      syndrome. The majority of authors consider ankyloblepharon, ectodermal dysplasia
      and orofacial clefting as cardinal signs. They are all are present in the case
      reported.

PMID- 16910924
TI  - Salivary interleukin-6 and tumor necrosis factor alpha in patients with drug
      induced xerostomia.
AB  - It is well known that cytokines are involved in the homeostasis of oral cavity
      and that altered levels of either serum and/or salivary cytokines have been found
      in certain oral/systemic diseases. So far, cytokines in connection with
      xerostomia have been investigated in patients with Sjogren's syndrome. We wanted
      to find out whether drugs themselves influence salivary glands, which would
      result in altered cytokine level or whether xerostomia itself of different causes
      leads to the changes in salivary cytokine levels. Therefore, the aim of this
      study was to evaluate levels of salivary interleukin-6 (IL-6) and tumor necrosis
      factor (TNF)-alpha in 30 patients with drug-induced xerostomia, age range 29-84
      and mean 63.9 years. Control group consisted of 30 healthy participants, age
      range 30-82 years and mean age 65.2 years. Enzyme-linked immunoassay was
      performed on commercially available kits. Statistical analysis was performed by
      use of Student's test. No significant differences in salivary IL-6 and TNF-alpha
      between patients with drug-induced xerostomia when compared with the healthy
      controls were found (P < 0.05). We might conclude that drugs do not induce damage
      to the salivary glands which could be seen in altered salivary IL-6 and TNF-alpha
      levels and that xerostomia itself, induced by drugs does not alter levels of the
      investigated salivary cytokines.

PMID- 16910925
TI  - Characterization of Bacillus subtilis strains in Thua nao, a traditional
      fermented soybean food in northern Thailand.
AB  - AIMS: To clarify the diversity of Bacillus subtilis strains in Thua nao that
      produce high concentrations of products useful in food manufacturing and in
      health-promoting compounds. METHOD AND RESULTS: Production of amylase, protease,
      subtilisin NAT (nattokinase), and gamma-polyglutamic acid (PGA) by the Bacillus
      subtilis strains in Thua nao was measured. Productivity of protease NAT by these
      strains tended to be higher than by Japanese commercial natto-producing strains.
      Molecular diversity of isolated strains was analysed via randomly amplified
      polymorphic DNA-PCR fingerprinting. The strains were divided into 19 types,
      including a type with the same pattern as a Japanese natto-producing strain.
      CONCLUSION: B. subtilis strains that could be a resource for effective production
      of protease, amylase, subtilisin NAT, or PGA were evident in Thua nao produced in
      various regions in northern Thailand. SIGNIFICANCE AND IMPACT OF THE STUDY: This
      study clearly demonstrated the value of Thua nao as a potential resource of food
      processing enzymes and health-promoting compounds.

PMID- 16910926
TI  - Different antibacterial actions of isoflavones isolated from Erythrina
      poeppigiana against methicillin-resistant Staphylococcus aureus.
AB  - AIMS: To screen six isoflavones isolated from Erythrina poeppigiana (Leguminosae)
      for their antibacterial activity against methicillin-resistant Staphylococcus
      aureus (MRSA). METHODS AND RESULTS: Stem bark of E. poeppigiana was macerated
      with acetone and the methylene chloride-soluble fraction of the residue was
      applied to repeated silica gel column chromatography and eluted. Minimum
      inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were
      determined by a broth dilution method. Inactive compounds that failed inhibiting
      bacterial growth at 25 microg ml(-1) were further investigated for their
      combination effects with methicillin and oxacillin. Of the isolated isoflavones,
      5,7,4'-trihydroxy-8,3'-di(gamma,gamma-dimethylallyl)isoflavone (isolupalbigenin)
      exhibited the highest anti-MRSA activity (MICs: 1.56-3.13 microg ml(-1); MBCs:
      6.25-12.5 microg ml(-1)), followed by 5,7,4'-trihydroxy-6-gamma,gamma
      dimethylallylisoflavone (erythrinin B). Inactive compounds were combined with
      methicillin or oxacillin, 5,4'-dihydroxy-(3'',4''-dihydro-3''-hydroxy)-2'',2''
      dimethylpyrano[5'',6'':6,7]isoflavone (M-Wi-2) intensifying the susceptibility of
      MRSA strains to these antibiotics. In all but one strain, the MIC values of
      methicillin were reduced from > or =100 to 6.25-12.5 microg ml(-1) in the
      presence of M-Wi-2 (25 microg ml(-1)). CONCLUSIONS: Isoflavones from E.
      poeppigiana showed two different antibacterial activities against MRSA: direct
      growth inhibition and intensification of methicillin sensitivity. SIGNIFICANCE
      AND IMPACT OF THE STUDY: Isolupalbigenin and M-Wi-2 could lead to the development
      of compounds for new approaches against MRSA infection.

PMID- 16910927
TI  - Identification of Vibrio harveyi using PCR amplification of the toxR gene.
AB  - AIMS: The aim of this study was to develop an effective method for the
      identification of Vibrio harveyi based on using the toxR gene as a taxonomic
      marker. METHODS AND RESULTS: Primers for the toxR gene were designed for
      specificity to V. harveyi, and incorporated in a polymerase chain reaction (PCR).
      The results of the PCR, which took <5 h from DNA extraction to amplification,
      revealed positive amplification of the toxR gene fragment in 20 V. harveyi
      isolates including type strains, whereas DNA from 23 other Vibrionaceae type
      strains and 13 Vibrio parahaemolyticus strains were negative. The detection limit
      of the PCR was 4.0 x 10(3) cells ml(-1). In addition, the technique enabled the
      recognition of V. harveyi from diseased fish. CONCLUSIONS: The PCR was specific
      and sensitive, enabling the identification of V. harveyi within 5 h. SIGNIFICANCE
      AND IMPACT OF THE STUDY: The PCR allowed the rapid and sensitive detection of V.
      harveyi.

PMID- 16910928
TI  - Media- and method-dependent variations in minimal inhibitory concentrations of
      antiplaque agents on oral bacteria.
AB  - AIMS: To determine minimal inhibitory concentrations (MICs) and the percentage of
      nonsusceptible bacteria-- those still cultivable above a threshold concentration-
      in human supragingival dental plaque and saliva for antiplaque/antimicrobial
      agents including triclosan (TCS) and trichlorocarbanilide (TCC), and a new
      potential antimicrobial, 2-t-butyl-5-(4-t-butylphenyl)-phenol (DTBBP). METHODS
      AND RESULTS: Broth and agar dilution-based MIC tests were performed using 28 oral
      and nonoral bacterial strains representing 17 species. MICs for TCS were lowest
      and more than 100-fold lower than DTBBP (P < 0.0005) by both methods. MICs for
      TCS were lower in broth-based tests compared with TCC. The additions of
      defibrinated blood to agar and horse serum to broth increased MICs--in the case
      of TCS, 10- to 15-fold. Significantly higher proportions of nonsusceptible plaque
      and salivary bacteria were recovered from agar media containing DTBBP or TCC
      compared with TCS (P < 0.05). CONCLUSIONS: TCS is a more effective antimicrobial
      agent than either TCC or DTBBP as determined by in vitro testing. SIGNIFICANCE
      AND IMPACT OF THE STUDY: The utility of in vitro testing for antiplaque agents as
      a predictor of in vivo efficacy is affected by the methods used.

PMID- 16910929
TI  - Production of cellulase by Aspergillus niger biofilms developed on polyester
      cloth.
AB  - AIMS: To compare cellulase production by Aspergillus niger ATCC 10864 biofilms on
      polyester cloth and freely suspended cultures in shaken flasks and
      microbioreactors of bubble column type. METHODS AND RESULTS: Both shaken flasks
      and oxygenated microbioreactors containing 40 ml of production medium were used
      to compare cellulase secretion by free mycelium and biofilm cultures. Free
      mycelium cultures grew better in flasks than in microbioreactors producing
      compact and fluffy pellets, respectively, while the opposite was found for
      biofilm cultures without any visible change in biofilm morphology. Cellulase
      activities and volumetric productivities attained by biofilms in flask cultures
      were 70% higher than that produced by free mycelium cultures and threefold higher
      when biofilms were grown in microbioreactors. CONCLUSIONS: Fungal biofilms
      developed on polyester cloth in both flasks and microbioreactors produce higher
      cellulase yields and volumetric productivities than free mycelium cultures at
      lower biomass levels. SIGNIFICANCE AND IMPACT OF THE STUDY: The results of the
      present study are of commercial and biological interest. All productivity
      parameters revealed that fungal biofilms may be used for the production of
      cellulase and other proteins in various types of bioreactors. Moreover, they may
      be used as model systems to study differential gene expression related to cell
      adhesion.

PMID- 16910930
TI  - Citric acid production by Aspergillus niger on wet corn distillers grains.
AB  - AIMS: To determine which citric acid-producing strain of Aspergillus niger
      utilized wet corn distillers grains most effectively to produce citric acid.
      METHODS AND RESULTS: Citric acid and biomass production by the fungal strains
      were analysed on the untreated grains or autoclaved grains using an enzyme assay
      and a gravimetric method respectively. Fungal citric acid production on the
      grains was found to occur on the untreated or autoclaved grains. The highest
      citric acid level on the grains was produced by A. niger ATCC 9142. The
      autoclaved grains supported less citric acid production by the majority of
      strains screened. Biomass production by the fungal strains on the untreated or
      autoclaved grains was quite similar. The highest citric acid yields for A. niger
      ATCC 9142, ATCC 10577, ATCC 11414, ATCC 12846 and ATCC 26550 were found on the
      untreated grains. Treatment of the grains had little effect on citric acid yields
      based on reducing sugars consumed by A. niger ATCC 9029 and ATCC 201122.
      CONCLUSIONS: It is feasible for citric acid-producing strains of A. niger to
      excrete citric acid on wet corn distillers grains whether the grains are treated
      or untreated. The most effective citric acid-producing strain of A. niger was
      ATCC 9142. SIGNIFICANCE AND IMPACT OF THE STUDY: The study shows that the ethanol
      processing co-product wet corn distillers grains could be utilized as a substrate
      for the commercial production of citric acid by A. niger without treatment of the
      grains.

PMID- 16910931
TI  - Molecular characterization of Enterococcus faecium isolated from hospitalized
      patients in Korea.
AB  - AIMS: Multilocus sequence typing (MLST) was performed for vancomycin-resistant
      Enterococcus faecium (VREF) from diverse geographical areas in Korea to obtain
      insights into the genetic relationships with other molecular profiles. To
      understand the diversity of lineages, vancomycin-susceptible E. faecium (VSEF)
      were included. METHODS AND RESULTS: A total of 60 E. faecium isolates were
      analysed by MLST and esp profile. Molecular typing of Tn1546 of 30 VREF strains
      was evaluated by overlapping PCR of Tn1546 and DNA sequencing. Seven sequence
      types (ST) were found among 30 VSEF isolates, and four STs were found among 30
      VREF isolates. The types most frequently encountered were ST 78 (26 isolates) and
      ST 203 (16 isolates). Of the 60 E. faecium isolates, 35 isolates were positive
      for the esp gene. On molecular typing of Tn1546, all VREF isolates were divided
      into four main types. Strains with the same ST showed divergence in Tn1546 types
      and strains with the same Tn1546 type represented different STs. CONCLUSIONS: An
      association between Tn1546 typing and MLST was not found. SIGNIFICANCE AND IMPACT
      OF THE STUDY: These results suggest that the horizontal spread of Tn1546 between
      strains plays a major role in the dissemination of vancomycin resistance in
      Korea.

PMID- 16910933
TI  - Combined use of 16S ribosomal DNA and automated ribosomal intergenic spacer
      analysis to study the bacterial community in catfish ponds.
AB  - AIMS: To apply culture-independent techniques to explore the bacterial community
      composition in catfish pond water. METHODS AND RESULTS: 16S rDNA libraries were
      constructed and sequenced from 15 pond water samples. Automated ribosomal
      intergenic spacer analysis (ARISA) was used to fingerprint each bacterial
      community. A broad diversity in bacterial species composition was found by 16S
      rDNA analysis. Alphaproteobacteria was the most represented class in all ponds,
      followed by Gammaproteobacteria and Gram-positive high G + C content bacteria.
      Uniqueness of bacterial communities from each individual pond was confirmed by
      ARISA. Catfish pathogens were detected sporadically. CONCLUSIONS: Bacterial
      communities in a catfish aquaculture setting can vary from pond to pond at one
      given point. No correlation could be made between bacteria composition and fish
      strain or between bacterial profile and the presence of catfish pathogens in a
      particular pond. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report
      showing the composition of bacterial communities in catfish ponds. Fish health
      specialists and catfish aquaculture managers should be aware of the wide
      differences in bacterial communities between ponds and include this variable in
      fish husbandry practices.

PMID- 16910932
TI  - Genetic labelling and application of the isoproturon-mineralizing Sphingomonas
      sp. strain SRS2 in soil and rhizosphere.
AB  - AIMS: To construct a luxAB-labelled Sphingomonas sp. strain SRS2 maintaining the
      ability to mineralize the herbicide isoproturon and usable for monitoring the
      survival and distribution of strain SRS2 on plant roots in laboratory systems.
      METHODS AND RESULTS: We inserted the mini-Tn5-luxAB marker into strain SRS2 using
      conjugational mating. In the transconjugant mutants luciferase was produced in
      varying levels. The mutants showed significant differences in their ability to
      degrade isoproturon. One luxAB-labelled mutant maintained the ability to
      mineralize isoproturon and was therefore selected for monitoring colonization of
      barley roots. CONCLUSIONS: We successfully constructed a genetically labelled
      isoproturon-mineralizing-strain SRS2 and demonstrated its ability to survive in
      soil and its colonization of rhizosphere. SIGNIFICANCE AND IMPACT OF THE STUDY:
      The construction of a luxAB-labelled strain SRS2 maintaining the degradative
      ability, provides a powerful tool for ecological studies serving as the basis for
      evaluating SRS2 as a bioremediation agent.

PMID- 16910934
TI  - Presence of Shiga toxin-producing Escherichia coli O157:H7 in living layer hens.
AB  - AIMS: To evaluate the presence of Shiga toxin-producing strains of Escherichia
      coli (STEC) of the O157:H7 serotype in living layer hens so as to analyse the
      role of this avian species as potential reservoir. METHODS AND RESULTS: Cloacal
      swabs were collected between November 2004 and November 2005 from four intensive
      management layer hen farms and analysed for STEC O157:H7 by immunomagnetic
      separation methods and multiplex polymerase chain reaction for stx1 and/or stx2,
      the E. coli attaching and effacing (eae) and hly genes. STEC was detected in 26
      of the 720 samples. CONCLUSIONS: The layer hens analysed were shown to carry STEC
      O157:H7. The presence of this bacterium in living layer hen farms investigated
      did not result in any detectable increase in gastrointestinal disease in this
      species. SIGNIFICANCE AND IMPACT OF THE STUDY: Living layer hens are a novel
      potential reservoir of E. coli O157:H7.

PMID- 16910935
TI  - Application of a microfluidic device for counting of bacteria.
AB  - AIMS: To develop a miniaturized analytical system for counting of bacteria.
      METHODS AND RESULTS: Escherichia coli cells were used throughout the experiments.
      The system consists of a microfluidic chamber, a fluorescence microscope with a
      charge-coupled device (CCD) camera and syringe pumps. The chamber was made of a
      silicone rubber (30 x 30 mm and 4 mm high). The E. coli cells were flowed from a
      micro-nozzle fabricated in the chamber and detected with the CCD camera. The
      individual cells were indicated as signal peaks on a computer. The cell counts
      showed a good correlation compared with that of a conventional plate counting
      method, and results of the simultaneous detection of live and dead cells were
      also presented. CONCLUSIONS, SIGNIFICANCE AND IMPACT OF THE STUDY: The system
      having a small disposable nozzle has the advantages for low cost and safe medical
      or environmental analysis, when compared with a conventional flow cytometer. This
      is the first step of the development of a one-chip microbe analyzer.

PMID- 16910936
TI  - Microbiological study of cosmetic products during their use by consumers: health
      risk and efficacy of preservative systems.
AB  - AIM: To evaluate the microbial contamination of 91 cosmetics (23 o/w emulsions,
      47 tensiolytes, 21 aqueous pastes) in three different states of use (intact, in
      use, ending product) and the protection efficacy of the preservative systems most
      frequently used in the analysed cosmetic formulations. METHODS AND RESULTS: Total
      bacterial count, isolation and identification of pathogenic isolates were
      performed on the collected cosmetics. About 10.6% of tensiolytes (13.5% bath
      foam, 6.7% shampoo, 10% liquid soaps) were contaminated by Staphylococcus
      warneri, Staphylococcus epidermidis and Pseudomonas putida. The efficacy of the
      preservative systems of two cosmetic products, tested against standard micro
      organisms (Staphylococcus aureus ATCC 4338 and Pseudomonas aeruginosa ATCC 9027)
      and two isolates from cosmetics in this study (S. epidermidis and P. putida),
      satisfied the Cosmetics, Toiletries, and Fragrance Association and Official
      Italian Pharmacopeia criteria, while only one tested cosmetic respected the Rapid
      Challenge Test criterion. CONCLUSIONS: Contaminated cosmetic products are
      relatively uncommon, but some products, unable to suppress the growth of several
      micro-organisms, represent a potential health hazard. SIGNIFICANCE AND IMPACT OF
      THE STUDY: The challenge test may be performed not only during the preparation of
      the preservative system in the intact cosmetics, but also be used to evaluate the
      protection efficacy during their use.

PMID- 16910937
TI  - Growth inhibition of bloom-forming cyanobacterium Microcystis aeruginosa by rice
      straw extract.
AB  - AIMS: To inhibit the growth of the bloom-forming cyanobacterium Microcystis
      aeruginosa using a rice straw extract. METHODS AND RESULTS: The cell numbers of
      the algal strain M. aeruginosa UTEX 2388 significantly decreased after treatment
      with different concentrations (0.01, 0.1, 1 and 10 mg l(-1)) of a rice straw
      extract for an 8-day cultivation period. Among seven tested allelochemicals from
      rice straw, salicylic acid at 0.1 mg l(1) exhibited the highest allelopathic
      activity (26%) on day 8. A synergistic effect on algal growth inhibition was
      found when adding two or three phenolic compounds from the rice straw.
      CONCLUSIONS: The growth of M. aeruginosa was inhibited by rice straw extract
      concentrations ranging from 0.01 to 10 mg l(1). This activity was due to the
      synergistic effects of various phenolic compounds in the rice straw. SIGNIFICANCE
      AND IMPACT OF THE STUDY: The identification of rice straw as an effective
      material for the growth inhibition of M. aeruginosa implies it may have the
      potential to be used as an environment-friendly biomaterial for controlling the
      algal bloom of M. aeruginosa in eutrophic water.

PMID- 16910938
TI  - Evaluation of ALOA plating medium for its suitability to recover high pressure
      injured Listeria monocytogenes from ground chicken meat.
AB  - AIMS: To evaluate a chromogenic plating medium for the isolation of sublethally
      injured cells of Listeria monocytogenes from processed foods. METHODS AND
      RESULTS: The inactivation of L. monocytogenes at pressures up to 400 MPa and 12
      degrees C in ground chicken meat was employed to examine the recovery of high
      pressure injured cells. Before and after different repair incubation periods at
      30 degrees C in a nonselective broth, samples were plated onto a selective and
      differential agar [Agar Listeria according to Ottaviani and Agosti (ALOA)] and in
      the same medium supplemented with 4% sodium chloride (ALOA-S), and incubated at
      37 degrees C. Sublethally injured cells were able to grow when directly plated
      onto the ALOA medium, without a previous repair incubation period. However, only
      uninjured cells grew on the ALOA-S medium. CONCLUSIONS: Sublethally injured cells
      of L. monocytogenes can be quantified by subtracting counts on ALOA-S medium from
      counts on ALOA medium. SIGNIFICANCE AND IMPACT OF THE STUDY: Possible
      applications include direct enumeration on ALOA of stressed cells of L.
      monocytogenes in foods with more than 100 colony forming units per gram.

PMID- 16910940
TI  - Use of a putative transcriptional regulator gene as target for specific
      identification of Staphylococcus epidermidis.
AB  - AIMS: To investigate the use of a Staphylococcus epidermidis transcriptional
      regulator gene as target for species-specific determination. METHODS AND RESULTS:
      Staph. epidermidis genes encoding putative transcriptional regulators were
      retrieved from GenBank and those showing no homology with other bacterial
      sequences were selected. Of the four PCR primer sets analysed, the primers
      Serp0107F/R from serp0107 amplified a specific product of 581 bp from Staph.
      epidermidis DNA only, and they did not cross-react in PCR with nonepidermidis
      staphylococci and other common bacteria. CONCLUSION: Being uniquely present in
      Staph. epidermidis, putative transcriptional regulator gene serp0107 offers a
      valuable target for specific identification of Staph. epidermidis. SIGNIFICANCE
      AND IMPACT OF THE STUDY: As a member of a specialized gene group, putative
      transcriptional regulator gene serp0107 may be important to Staph. epidermidis
      adaptation to its niche environment. Further analysis of serp0107 and its related
      protein may help reveal new insights on the molecular regulation of Staph.
      epidermidis survival and virulence.

PMID- 16910939
TI  - Comparative study of in vitro methods to analyse the antifungal activity of
      propolis against yeasts isolated from patients with superficial mycoses.
AB  - AIM: To test a total of 15 strains belonging to four species of yeasts by
      different in vitro methods against propolis and itraconazole (ITC). METHODS AND
      RESULTS: Three methods were compared for susceptibility testing of yeast isolates
      to propolis: disc diffusion method, agar dilution method and National Committee
      for Clinical Laboratory Standards (NCCLS, M27A) broth microdilution method. ITC
      was selected as the antifungal agent for comparison study. Using the broth
      microdilution method, the geometric mean for MIC (microg ml(-1)) with regard to
      all isolates was < or =0.06 for propolis and < or =0.35 for ITC. The broth
      microdilution and the agar dilution methods were in good agreement (75%) for
      propolis against yeasts isolated from patients with superficial mycoses. Using
      the diffusion method, all strains showed a broad zone of inhibition at the first
      available reading time (24 or 48 h). An increase of MIC values was accompanied by
      a decrease of growth inhibition zone diameter. A favourable correlation was found
      between MIC and inhibition zone around the disc for propolis sample and the
      correlation coefficient was: r = -0.626 (P < 0.01). CONCLUSIONS: This study
      suggests the potential value of the agar dilution and disc diffusion method as a
      convenient alternative method for testing of yeasts to propolis. SIGNIFICANCE AND
      IMPACT OF THE STUDY: This study demonstrated that propolis and ITC were very
      active against yeasts from patients with superficial mycoses. The other prominent
      finding in this study is that RPMI 1640 with L-glutamine was the available broth
      for the in vitro susceptibility testing of yeasts.

PMID- 16910941
TI  - Medium components and culture conditions affect the thermotolerance of aerial
      conidia of fungal biocontrol agent Beauveria bassiana.
AB  - AIMS: To produce more thermotolerable conidia of Beauveria bassiana, a well-known
      fungal biocontrol agent, by optimizing the medium components and culture
      conditions. METHODS AND RESULTS: The conidia produced on media including 0.5-6%
      glucose, sucrose or starch as carbon source and 50-300-microg ml(-1) Cu2+, Zn2+,
      Mn2+ or Fe3+ as additive to Sabouraud dextrose medium at 15-30 degrees C, pH 4-8
      or KCl-adjusted water availabilities were exposed to 30-min wet heat stress at 48
      degrees C. The medium components for conidial production with greatly enhanced
      thermotolerance included 4% glucose as optimum or 1% starch as alternative for
      the carbon source and < or =50-microg ml(-1) Mn2+ for the metal additive. The
      culture conditions were optimized as 25 degrees C and pH 5-6. Conidial
      thermotolerance decreased remarkably when sucrose and Fe3+ or Cu2+ were used in
      the cultures, but altered slightly when 50-200-microg ml(-1) Zn2+ were included.
      CONCLUSIONS: The tolerance of B. bassiana conidia to the thermal stress was
      significantly affected by the medium composition and culture conditions under
      which the conidia were produced. SIGNIFICANCE AND IMPACT OF THE STUDY: Proper
      treatment of small grains as mass production substrates for more glucose release
      and supplement of glucose or 50-microg ml(-1) Mn2+ are possible means to
      enhancing conidial thermotolerance and field persistence for improved insect
      control.

PMID- 16910942
TI  - Identification of intestinal bacteria from Japanese flounder (Paralichthys
      olivaceus) and their ability to digest chitin.
AB  - AIMS: The aim of the present study was to clarify the taxonomic status of
      intestinal bacteria isolated from Japanese flounder (Paralichthys olivaceus) and
      describe their ability to digest chitin. METHODS AND RESULTS: Phylogenetic
      analysis based on 16S ribosomal DNA (rDNA) sequences showed that 82
      representative isolates were closely related to three major species of marine
      vibrios, Vibrio scophthalmi-Vibrio ichthyoenteri group (41 isolates), Vibrio
      fischeri (39 isolates) and Vibrio harveyi (two isolates), with similarities of
      97.2-99.8%, 96.4-100% and 98.6-99.5% respectively. These findings indicate that
      V. scophthalmi-V. ichthyoenteri group is indigenous to the intestinal tract of
      Japanese flounder. Moreover, the ability of 82 isolates to digest chitin was
      examined using the agar plate method and PCR amplification of the chiA gene. The
      two V. harveyi isolates and 36 of 41 V. scophthalmi-V. ichthyoenteri isolates
      digested chitin and were chiA PCR positive, whereas all 39 V. fischeri isolates
      digested chitin but were chiA PCR negative. CONCLUSIONS: Intestinal bacteria from
      Japanese flounder were mainly composed of Vibrio scophthalmi-V. ichthyoenteri
      group and V. fischeri. Taken together, the results showed that 81 of 82 isolates
      could digest chitin. However, only 38 of these isolates possessed a chiA
      homologue which could be identified by PCR. SIGNIFICANCE AND IMPACT OF THE STUDY:
      The present study shows that Japanese flounder harbours bacteria of the V.
      scophthalmi-V. ichthyoenteri group, and these results are similar to what has
      been found for turbot (Scophthalmus maximus).

PMID- 16910943
TI  - Application of a novel polyphasic approach to study the lactobacilli composition
      of sourdoughs from the Abruzzo region (central Italy).
AB  - AIMS: To characterize the lactobacilli community of 20 sourdoughs using a novel
      polyphasic approach. METHODS AND RESULTS: A polyphasic approach, consisting of a
      two-step multiplex polymerase chain reaction (PCR) system, 16S rRNA gene sequence
      analysis and physiological features, was applied to identify 127 isolates,
      representing about 37% of the presumptive lactobacilli collected from sourdough
      samples. Multiplex PCR successfully identified 111 isolates, while 16S rRNA gene
      sequencing was applied for the other 16 isolates, two of which could not be
      associated with any previously described lactic acid bacteria (LAB) species.
      Strain diversity was evaluated by phenotypic and random amplified polymorphic DNA
      PCR analysis. Molecular detection of Lactobacillus group species was also
      performed on total DNA extracted from the doughs. CONCLUSIONS: Abruzzo region
      sourdough lactobacilli biodiversity, reflected in both Lactobacillus species
      composition and strain polymorphism, is similar to that of other Italian regions
      and is a source of novel LAB species. SIGNIFICANCE AND IMPACT OF THE STUDY:
      Within culture-independent methods, multiplex PCR is a rapid tool to study the
      lactobacilli population of sourdoughs.

PMID- 16910945
TI  - Mobilising modern facts: health technology assessment and the politics of
      evidence.
AB  - Conventional models of 'evidence' for clinical practice focus on the role of
      randomised controlled clinical trials and systematic reviews as technologies that
      promote a specific model of rigour and analytic accountability. The assumption
      that runs through the disciplinary field of health technology assessment (HTA),
      for example, is that the quantification of evidence about cost and clinical
      effectiveness is central to rational policy-making and healthcare provision. But
      what are the conditions in which such knowledge is mediated into decision-making
      contexts, and how is it understood and used when it gets there? This paper
      addresses these questions by examining a series of meetings and seminars attended
      by senior clinical researchers, social care and health service managers in the UK
      between 1998-2004, and sessions of the House of Commons Health Committee held in
      2001 and 2005. These provide contexts in which questions about the value and
      utility of evidence produced within the frame of HTA were explored in relation to
      parallel questions about the design, evaluation and implementation of
      telemedicine and telecare systems. The paper points to the ways that evidence
      generated in the normative frame of HTA was increasingly seen as one-dimensional
      and medicalised knowledge that failed to respond to the contingencies of everyday
      practice in health and social care settings.

PMID- 16910946
TI  - Exclusive versus everyday forms of professional knowledge: legitimacy claims in
      conventional and alternative medicine.
AB  - In this paper I present a model of professional knowledge forms that accounts for
      the different, and sometimes contradictory, ways in which medical doctors (MDs)
      and various complementary and alternative medicine (CAM) practitioners define
      their competencies and make legitimacy claims. The first section provides a
      schema for problematising knowledge and its relationship to legitimacy by
      distinguishing between the context, form and content of professional knowledge. I
      draw particularly upon Jamous and Peloille's (1970) distinction between the
      technical or indeterminate forms of professional knowledge. I argue that their
      characterisation might be enriched by attending to dimensions of 'exclusive'
      versus 'everyday' knowledge forms. In particular, I point out that both technical
      and indeterminate forms are amenable to exclusion, or conversely can be made
      accessible as everyday knowledge. Both forms can thus be employed in attempts to
      legitimate professional practice. In the final section, I map the current context
      of CAM and biomedicine onto this expanded professional knowledge map.

PMID- 16910947
TI  - Prospective effect of community distress and subcultural orientation on mortality
      following life-threatening diseases in later life.
AB  - We conducted a prospective and contextual study to examine the effects of
      community social-economic-physical distress and subcultural orientation on
      mortality following onset of 13 life-threatening diseases in later life. We also
      examined the inter-relationship between the effects of community social, economic
      and physical distress (i.e. poverty, physical disorder and low collective
      efficacy) and subcultural orientation (i.e. anomie and tolerance of risk
      behaviour) on the survival chances of seriously ill older patients. Three data
      sources were combined to construct the working sample: 1990 Census data, the 1994
      95 PHDCN-CS, and the COSI data. Fifty-one ZIP code areas in Chicago and 12,672
      elderly patients were studied. Community distress (HR = 1.04; 95% CI = (1.01,
      1.07)) and anomie (HR = 1.26; 95% CI = (1.02, 1.54)) are found to be
      significantly and positively associated with a higher hazard of death. Moreover,
      community anomie contributes to the effect of community distress on post
      hospitalisation mortality. The social, economic, physical and cultural
      environment in which people live appears to exert a significant impact on whether
      older people facing life-threatening illness live or die.

PMID- 16910948
TI  - 'Pressure of life': ethnicity as a mediating factor in mid-life and older
      peoples' experience of high blood pressure.
AB  - Hypertension is a common condition which disproportionately affects African
      Caribbean people in England, yet this experience is rarely reported in the
      literature. Whilst a body of literature exists that explores chronic illness
      experience, little attention is paid to hypertension, nor to ethnicity as a
      mediating concept in chronic illness experience. This paper explores the meaning
      and consequences of hypertension for African Caribbean people residing in
      England. The study conducted was a qualitative study, informed by the
      ethnographic tradition. The study methods included the conduct of two focus group
      interviews (10 participants), 21 in-depth interviews and five vignette
      interviews. Thirty-six people in total participated in the study, both men and
      women, aged between 37 and 82 years (median age = 59.5 years) in two English
      cities. The sample was generated by contacting GP surgeries, community groups and
      associations and included economically active and retired people. The narrative
      accounts provided illuminate the personal biographies of the mid-life and older
      participants in the study, providing evidence as to how issues such as ethnicity,
      migration, cultural adaptation, racism and discrimination may impact upon the
      chronic illness experience. Participants' understandings of their self-defined
      condition of high blood pressure differed greatly from medical conceptualisations
      of the condition of hypertension. The implications of the study are that in order
      to provide effective health and social care for individuals of African Caribbean
      origin with hypertension, care-providers require insight into how migration and
      cultural adaptation may create major disruption to an individual's life
      trajectory, to which the subsequent diagnoses of chronic illness are relative in
      terms of the individual's response and adaptation.

PMID- 16910949
TI  - Breaking the ceremonial order: patients' and doctors' accounts of removal from a
      general practitioner's list.
AB  - The removal of patients from general practitioners' (GPs) lists in the UK offers
      important sociological insights into what happens when the doctor-patient
      relationship 'goes wrong'. An interactionist analysis shows how removers
      (doctors) and removed (patients) strategically invoke 'rules of conduct' to
      account for difficulties in the doctor-patient relationship and for GPs'
      decisions to end their relationships with patients. In this paper we extend this
      analysis through recourse to Bourdieu's theory of practice, by juxtaposing
      'paired' accounts of the same removal event by both remover and removed. Our
      analysis demonstrates the unthinking or non-reflective nature of people's
      understanding of the rules governing social interactions, but also demonstrates
      how apparent rule violations make the rules explicit and expose patterns of power
      distribution. We argue that removal of patients amounts to a strategic exercise
      of symbolic power by GPs, and that this is experienced as an overtly violent
      symbolic act by patients. A theoretical reconciliation of interactionist theories
      of the doctor-patient relationship with Bourdieu's theory of practice is both
      possible and profitable, providing a micro-macro link in which issues of capital
      and power within the health (care) field are brought to the fore.

PMID- 16910950
TI  - Review essay: avoiding conventional understandings: the enduring legacy of Eliot
      Freidson.

PMID- 16910958
TI  - The evolution of cooperation and altruism--a general framework and a
      classification of models.
AB  - One of the enduring puzzles in biology and the social sciences is the origin and
      persistence of intraspecific cooperation and altruism in humans and other
      species. Hundreds of theoretical models have been proposed and there is much
      confusion about the relationship between these models. To clarify the situation,
      we developed a synthetic conceptual framework that delineates the conditions
      necessary for the evolution of altruism and cooperation. We show that at least
      one of the four following conditions needs to be fulfilled: direct benefits to
      the focal individual performing a cooperative act; direct or indirect information
      allowing a better than random guess about whether a given individual will behave
      cooperatively in repeated reciprocal interactions; preferential interactions
      between related individuals; and genetic correlation between genes coding for
      altruism and phenotypic traits that can be identified. When one or more of these
      conditions are met, altruism or cooperation can evolve if the cost-to-benefit
      ratio of altruistic and cooperative acts is greater than a threshold value. The
      cost-to-benefit ratio can be altered by coercion, punishment and policing which
      therefore act as mechanisms facilitating the evolution of altruism and
      cooperation. All the models proposed so far are explicitly or implicitly built on
      these general principles, allowing us to classify them into four general
      categories.

PMID- 16910959
TI  - Kinds of kindness: classifying the causes of altruism and cooperation.

PMID- 16910960
TI  - Reciprocity: you have to think different.

PMID- 16910961
TI  - Self-serving punishment and the evolution of cooperation.

PMID- 16910962
TI  - Limits of Hamilton's rule.

PMID- 16910963
TI  - How altruism evolves: assortment and synergy.

PMID- 16910964
TI  - Balancing synthesis with pluralism in sociobiology.

PMID- 16910965
TI  - Various remarks on Lehmann and Keller's article.

PMID- 16910966
TI  - Cooperating for direct fitness benefits.

PMID- 16910967
TI  - Facing the facts.

PMID- 16910968
TI  - Cooperation and conflict during evolutionary transitions in individuality.

PMID- 16910969
TI  - Models of cooperation.

PMID- 16910970
TI  - The evolution of cooperation and altruism: the basic conditions are simple and
      well known.

PMID- 16910971
TI  - Cooperation within and among species.

PMID- 16910972
TI  - Modelling social evolution: the relative merits and limitations of a Hamilton's
      rule-based approach.

PMID- 16910973
TI  - The economics of altruism and cooperation in class-structured populations: what's
      in a cost? What's in a benefit?

PMID- 16910975
TI  - Heritability and fitness-related consequences of squid personality traits.
AB  - Dumpling squid, Euprymna tasmanica, show consistent individual differences in
      behaviour that can be classified according to indices reflecting shy-bold,
      activity and reactivity responses. Using crosses of wild-caught single males to
      multiple females with known behavioural phenotypes, this study estimated patterns
      of additive genetic and residual variance in these behavioural traits from
      offspring of squid in two contexts, a threat (antipredator) and feeding
      (foraging) test. Genetic contributions to behavioural expression were dependent
      on test context. Behaviours in antipredator contexts had significant
      heritabilities (h(2) = 0.2-0.8) while behaviours from foraging contexts had
      lesser additive genetic and greater residual components (h(2) = 0.05-0.08).
      Personality trait variation in females was not related to her fecundity. Female
      boldness in foraging situations, which co-varied with body size, explained small
      but significant variation ( approximately 21%) in brood hatching success, while
      successful fertilization was determined by positive assortion of mate pairs
      according to their shy-bold phenotype. These results are discussed in terms of
      the ecological and evolutionary significance of animal "personality" traits in
      wild populations of animals.

PMID- 16910976
TI  - Theoretical influence of female mating status and remating propensity on male
      sperm allocation patterns.
AB  - Theoretical models predict that males should allocate more sperm in matings where
      the immediate risk of sperm competition is high. It has therefore often been
      argued that males should invest less sperm in matings with virgin females
      compared with matings with already mated females. However, with relatively
      polyandrous females, high sperm competition risk will covary with high sperm
      competition intensity leading to more unpredictable conditions, as high
      competition intensity should favour smaller ejaculates. With the use of a genetic
      algorithm, we found that males should allocate more sperm in matings with virgin
      females when female mating frequency is relatively high, whereas low remating
      rates will select for higher effort in matings with nonvirgin females. At higher
      remating rates, first male sperm precedence favours larger ejaculates in matings
      with virgin females and second male precedence favours the reverse. These results
      shed some light on several findings that have been difficult to explain
      adaptively by the hitherto developed theory on sperm allocation.

PMID- 16910977
TI  - Parallel evolution of larval morphology and habitat in the snail-killing fly
      genus Tetanocera.
AB  - In this study, we sequenced one nuclear and three mitochondrial DNA loci to
      construct a robust estimate of phylogeny for all available species of Tetanocera.
      Character optimizations suggested that aquatic habitat was the ancestral
      condition for Tetanocera larvae, and that there were at least three parallel
      transitions to terrestrial habitat, with one reversal. Maximum likelihood
      analyses of character state transformations showed significant correlations
      between habitat transitions and changes in four larval morphological
      characteristics (cuticular pigmentation and three characters associated with the
      posterior spiracular disc). We provide evidence that phylogenetic niche
      conservatism has been responsible for the maintenance of aquatic-associated
      larval morphological character states, and that concerted convergence and/or gene
      linkage was responsible for parallel morphological changes that were derived in
      conjunction with habitat transitions. These habitat-morphology associations were
      consistent with the action of natural selection in facilitating the morphological
      changes that occurred during parallel aquatic to terrestrial habitat transitions
      in Tetanocera.

PMID- 16910978
TI  - High recombination frequency creates genotypic diversity in colonies of the leaf
      cutting ant Acromyrmex echinatior.
AB  - Honeybees are known to have genetically diverse colonies because queens mate with
      many males and the recombination rate is extremely high. Genetic diversity among
      social insect workers has been hypothesized to improve general performance of
      large and complex colonies, but this idea has not been tested in other social
      insects. Here, we present a linkage map and an estimate of the recombination rate
      for Acromyrmex echinatior, a leaf-cutting ant that resembles the honeybee in
      having multiple mating of queens and colonies of approximately the same size. A
      map of 145 AFLP markers in 22 linkage groups yielded a total recombinational size
      of 2076 cM and an inferred recombination rate of 161 kb cM(-1) (or 6.2 cM Mb(
      1)). This estimate is lower than in the honeybee but, as far as the mapping
      criteria can be compared, higher than in any other insect mapped so far. Earlier
      studies on A. echinatior have demonstrated that variation in division of labour
      and pathogen resistance has a genetic component and that genotypic diversity
      among workers may thus give colonies of this leaf-cutting ant a functional
      advantage. The present result is therefore consistent with the hypothesis that
      complex social life can select for an increased recombination rate through
      effects on genotypic diversity and colony performance.

PMID- 16910979
TI  - A change of expression in the conserved signaling gene MKK7 is associated with a
      selective sweep in the western house mouse Mus musculus domesticus.
AB  - Changes in gene expression are known to occur between closely related species,
      but it is not yet clear how many of these are due to random fixation of allelic
      variants or due to adaptive events. In a microarray survey between subspecies of
      the Mus musculus complex, we identified the mitogen-activated protein-kinase
      kinase MKK7 as a candidate for change in gene expression. Quantitative PCR
      experiments with multiple individuals from each subspecies confirmed a specific
      and significant up-regulation in the testis of M. m. domesticus. Northern blot
      analysis shows that this is due to a new transcript that is not found in other
      tissues, nor in M. m. musculus. A cis-trans test via allele specific expression
      analysis of the MKK7 gene in F1 hybrids between domesticus and musculus shows
      that the expression change is mainly caused by a mutation located in cis.
      Nucleotide diversity was found to be significantly reduced in a window of at
      least 20 kb around the MKK7 locus in domesticus, indicative of a selective sweep.
      Because the MKK7 gene is involved in modulating a kinase signalling cascade in a
      stress response pathway, it seems a plausible target for adaptive differences
      between subspecies, although the functional role of the new testis-specific
      transcripts will need to be further studied.

PMID- 16910980
TI  - Does inbreeding avoidance maintain gender dimorphism in Wurmbea dioica
      (Colchicaceae)?
AB  - The maintenance of females in gender dimorphic populations requires that they
      have a fitness advantage to compensate for their loss of male reproductive
      function. We assess whether inbreeding avoidance provides this advantage in two
      subdioecious Wurmbea dioica populations by estimating seed production,
      outcrossing rates and inbreeding depression. Fruiting males produced less than
      half as many seeds as females, owing to low outcrossing rates and early acting
      inbreeding depression. Inbreeding coefficients of fruiting males demonstrated
      that progeny were more inbred than their parents, implying that few selfed
      progeny reach maturity, as confirmed by inbreeding depression estimates that
      exceeded 0.85. In a glasshouse experiment, open-pollinated females exhibited a
      fitness advantage of 3.7 relative to fruiting males, but when we increased
      fruiting male outcrossing rate, female advantage was only 1.4. This reduced
      advantage is insufficient to maintain females if nuclear genes control sex. Thus,
      inbreeding avoidance could maintain females at high frequencies, although this is
      contingent upon high frequencies of fruiting males, which can be altered by
      environmentally determined gender plasticity.

PMID- 16910981
TI  - An evolutionary analysis of the relationship between spite and altruism.
AB  - We investigate the selective pressures on a social trait when evolution occurs in
      a population of constant size. We show that any social trait that is spiteful
      simultaneously qualifies as altruistic. In other words, any trait that reduces
      the fitness of less related individuals necessarily increases that of related
      ones. Our analysis demonstrates that the distinction between "Hamiltonian spite"
      and "Wilsonian spite" is not justified on the basis of fitness effects. We
      illustrate this general result with an explicit model for the evolution of a
      social act that reduces the recipient's survival ("harming trait"). This model
      shows that the evolution of harming is favoured if local demes are of small size
      and migration is low (philopatry). Further, deme size and migration rate
      determine whether harming evolves as a selfish strategy by increasing the fitness
      of the actor, or as a spiteful/altruistic strategy through its positive effect on
      the fitness of close kin.

PMID- 16910982
TI  - Testing the directionality of evolution: the case of chydorid crustaceans.
AB  - Although trends are of central interest to evolutionary biology, it is only
      recently that methodological advances have allowed rigorous statistical tests of
      putative trends in the evolution of discrete traits. Oligomerization is one such
      proposed trend that may have profoundly influenced evolutionary pathways in many
      types of animals, especially arthropods. It is a general hypothesis that repeated
      structures (such as appendage segments and spines) tend to evolve primarily
      through loss. Although largely untested, this principle of loss is commonly
      invoked in morphological studies of crustaceans for drawing conclusions about the
      systematic placements of taxa and about their phylogeny. We present a statistical
      evaluation of this hypothesis using a molecular phylogeny and character matrix
      for a family of crustaceans, the Chydoridae, analysed using maximum likelihood
      methods. We find that a unidirectional (loss-only) model of character evolution
      is a very poor fit to the data, but that there is evidence of a trend towards
      loss, with loss rates of structures being perhaps twice the rates of gain. Thus,
      our results caution against assuming loss a priori, in the absence of appropriate
      tests for the characters under consideration. However, oligomerization,
      considered as a tendency but not a rule, may indeed have had ramifications for
      the types of functional and ecological shifts that have been more common during
      evolutionary diversification.

PMID- 16910983
TI  - Reproductive isolation in a threespine stickleback hybrid zone.
AB  - In many estuarine sites, morphological and genetic differences between anadromous
      and freshwater threespine sticklebacks are maintained despite breeding in
      sympatry. Here, we investigate the maintenance of this morphological divergence
      in a natural hybrid zone in the River Tyne, Scotland. We provide a morphological
      description of the hybrid zone, and using a Bayesian MCMC approach, identified
      distinct anadromous and freshwater genetic clusters. Anadromous and freshwater
      sticklebacks breed in spatial and temporal sympatry in the lower reaches of the
      River Tyne. The frequency of hybrids within these sites (33%) indicates
      prezygotic isolation is not complete, and suggests that assortative mating is not
      strong. However, significant heterozygote deficit and cytonuclear disequilibrium
      in juveniles collected from sympatric sites confirms that barriers to gene flow
      exist between the morphs in the wild. In addition, we found no evidence of a
      directional bias in hybridisation, although hybrids with anadromous mothers were
      more common because anadromous females outnumbered freshwater females within the
      hybrid zone. We discuss the potential contribution of temporal, spatial, and
      sexual prezygotic barriers to the observed reproductive isolation as well as
      postzygotic selection against hybrid zygotes or fry.

PMID- 16910984
TI  - Morphological integration and adaptation in the snake feeding system: a
      comparative phylogenetic study.
AB  - A long-standing hypothesis for the adaptive radiation of macrostomatan snakes is
      that their enlarged gape--compared to both lizards and basal snakes--enables them
      to consume "large" prey. At first glance, this hypothesis seems plausible, or
      even likely, given the wealth of studies showing a tight match between maximum
      consumed prey mass and head size in snakes. However, this hypothesis has never
      been tested within a comparative framework. We address this issue here by testing
      this hypothesis in 12 monophyletic clades of macrostomatan snakes using recently
      published phylogenies, published maximum consumed prey mass data and
      morphological measurements taken from a large sample of museum specimens. Our
      nonphylogenetically corrected analysis shows that head width--independent of body
      size--is significantly related to mean maximum consumed prey mass among these
      clades, and this relationship becomes even more significant when phylogeny is
      taken into account. Therefore, these data do support the hypothesis that head
      shape is adapted to prey size in snakes. Additionally, we calculated a
      phylogenetically corrected morphological variance-covariance matrix to examine
      the role of morphological integration during head shape evolution in snakes. This
      matrix shows that head width strongly covaries with both jaw length and out-lever
      length of the lower jaw. As a result, selection on head width will likely be
      associated with concomitant changes in jaw length and lower jaw out-lever length
      in snakes.

PMID- 16910985
TI  - The effect of phenotypic plasticity on evolution in multipeaked fitness
      landscapes.
AB  - When facing the challenge of developing an individual that best fits its
      environment, nature demonstrates an interesting combination of two fundamentally
      different adaptive mechanisms: genetic evolution and phenotypic plasticity.
      Following numerous computational models, it has become the accepted wisdom that
      lifetime acclimation (e.g. via learning) smooths the fitness landscape and
      consequently accelerates evolution. However, analytical studies, focusing on the
      effect of phenotypic plasticity on evolution in simple unimodal landscapes, have
      often found that learning hinders the evolutionary process rather than
      accelerating it. Here, we provide a general framework for studying the effect of
      plasticity on evolution in multipeaked landscapes and introduce a rigorous
      mathematical analysis of these dynamics. We show that the convergence rate of the
      evolutionary process in a given arbitrary one-dimensional fitness landscape is
      dominated by the largest descent (drawdown) in the landscape and provide
      numerical evidence to support an analogous dominance also in multidimensional
      landscapes. We consider several schemes of phenotypic plasticity and examine
      their effect on the landscape drawdown, identifying the conditions under which
      phenotypic plasticity is advantageous. The lack of such a drawdown in unimodal
      landscapes vs. its dominance in multipeaked landscapes accounts for the seemingly
      contradictory findings of previous studies.

PMID- 16910986
TI  - Early maternal, genetic and environmental components of antioxidant protection,
      morphology and immunity of yellow-legged gull (Larus michahellis) chicks.
AB  - Maternal effects mediated by egg quality are important sources of offspring
      phenotypic variation and can influence the course of evolutionary processes.
      Mothers allocate to the eggs diverse antioxidants that protect the embryo from
      oxidative stress. In the yellow-legged gull (Larus michahellis), yolk antioxidant
      capacity varied markedly among clutches and declined considerably with egg laying
      date. Analysis of bioptic yolk samples from clutches that were subsequently
      partially cross-fostered revealed a positive effect of yolk antioxidant capacity
      on embryonic development and chick growth, but not on immunity and begging
      behaviour, while controlling for parentage and common environment effects. Chick
      plasma antioxidant capacity varied according to rearing environment, after
      statistically partitioning out maternal influences mediated by egg quality. Thus,
      the results of this study indicate that egg antioxidants are important mediators
      of maternal effects also in wild bird populations, especially during the critical
      early post-hatching phase.

PMID- 16910987
TI  - To eject or to abandon? Life history traits of hosts and parasites interact to
      influence the fitness payoffs of alternative anti-parasite strategies.
AB  - Hosts either tolerate avian brood parasitism or reject it by ejecting parasitic
      eggs, as seen in most rejecter hosts of common cuckoos, Cuculus canorus, or by
      abandoning parasitized clutches, as seen in most rejecter hosts of brown-headed
      cowbirds, Molothrus ater. What explains consistent variation between alternative
      rejection behaviours of hosts within the same species and across species when
      exposed to different types of parasites? Life history theory predicts that when
      parasites decrease the fitness of host offspring, but not the future reproductive
      success of host adults, optimal clutch size should decrease. Consistent with this
      prediction, evolutionarily old cowbird hosts, but not cuckoo hosts, have lower
      clutch sizes than related rarely- or newly parasitized species. We constructed a
      mathematical model to calculate the fitness payoffs of egg ejector vs. nest
      abandoner hosts to determine if various aspects of host life history traits and
      brood parasites' virulence on adult and young host fitness differentially
      influence the payoffs of alternative host defences. These calculations showed
      that in general egg ejection was a superior anti-parasite strategy to nest
      abandonment. Yet, increasing parasitism rates and increasing fitness values of
      hosts' eggs in both currently parasitized and future replacement nests led to
      switch points in fitness payoffs in favour of nest abandonment. Nonetheless, nest
      abandonment became selectively more favourable only at lower clutch sizes and
      only when hosts faced parasitism by a cowbird- rather than a cuckoo-type brood
      parasite. We suggest that, in addition to evolutionary lag and gape-size
      limitation, our estimated fitness differences based on life history trait
      variation provide new insights for the consistent differences observed in the
      anti-parasite rejection strategies between many cuckoo- and cowbird-hosts.

PMID- 16910988
TI  - Colourful male guppies produce faster and more viable sperm.
AB  - In guppies (Poecilia reticulata) precopulatory sexual selection (via female
      choice) and post-copulatory selection (via sperm competition) both favour males
      with relatively high levels of carotenoid (orange) pigmentation, suggesting that
      colourful males produce more competitive ejaculates. Here we test whether there
      is a positive association between male orange pigmentation and sperm quality. Our
      analysis of sperm quality focused on sperm swimming speeds (using CASA: computer
      assisted sperm analysis to estimate three parameters of sperm velocity in vitro),
      sperm viability (proportion of live sperm per stripped ejaculate) and sperm
      lengths. We found that males with relatively large areas of orange pigmentation
      had significantly faster and more viable sperm than their less ornamented
      counterparts, suggesting a possible link between dietary carotenoid intake and
      sperm quality. By contrast, we found no relationship between sperm length (head
      length and total sperm length) and male phenotype. These findings, in conjunction
      with previous work showing that highly ornamented male guppies sire higher
      quality offspring, suggest that female preference for colourful males and sperm
      competition work in concert to favour intrinsically higher quality males.

PMID- 16910989
TI  - Testing the pluralist approach to sex: the influence of environment on
      synergistic interactions between mutation load and parasitism in Daphnia magna.
AB  - Both deleterious mutations and parasites have been acknowledged as potential
      selective forces responsible for the evolutionary maintenance of sexual
      reproduction. The pluralist approach to sex proposes that these two factors may
      have to interact synergistically in order to stabilize sex, and one of the
      simplest ways this could occur is if parasites are capable of causing synergistic
      epistasis between mutations in their hosts. However, the effects of both
      deleterious mutations and parasitism are known to be influenced by a range of
      environmental factors, so the nature of the interaction may depend upon the
      organisms' environment. Using chemically mutated Daphnia magna lines, we examined
      the effects of mutation and parasitism under a range of temperature and food
      regimes. We found that although parasites were capable of causing synergistic
      epistasis between mutations in their hosts, these effects were dependent upon an
      interaction between parasite genotype and temperature.

PMID- 16910990
TI  - Silene tatarica microsatellites are frequently located in repetitive DNA.
AB  - The genomic distribution of microsatellites can be explained by DNA slippage,
      slippage like processes and base substitutions. Nevertheless, microsatellites are
      also frequently associated with repetitive DNA, raising the question of the
      relative contributions of these processes to microsatellite genesis. We show that
      in Silene tatarica about 50% of the microsatellites isolated by an enrichment
      cloning protocol are associated with repetitive DNA. Based on the flanking
      sequences, we distinguished seven different classes of repetitive DNA. PCR
      primers designed for the flanking sequences of an individual clone amplified a
      heterogeneous family of repetitive DNA. Despite considerable variation in the
      flanking sequence (pi = 0.108), the microsatellite repeats did not show any
      evidence for decay. Rather, we observed the emergence of a new repeat type that
      probably arose by mutation and was spread by replication slippage. In fact, a
      complete repeat type switch could be observed among the analysed clones. We
      propose that the analysis of microsatellite sequences embedded in repetitive DNA
      provides a hitherto largely unexplored tool to study microsatellite evolution.

PMID- 16910991
TI  - Host-parasite interactions for virulence and resistance in a malaria model
      system.
AB  - A rich body of theory on the evolution of virulence (disease severity) attempts
      to predict the conditions that cause parasites to harm their hosts, and a central
      assumption to many of these models is that the relative virulence of pathogen
      strains is stable across a range of host types. In contrast, a largely
      nonoverlapping body of theory on coevolution assumes that the fitness effects of
      parasites on hosts is not stable across host genotype, but instead depends on
      host genotype by parasite genotype interactions. If such genetic interactions
      largely determine virulence, it becomes difficult to predict the strength and
      direction of selection on virulence. In this study, we tested for host-by
      parasite interactions in a medically relevant vertebrate disease model: the
      rodent malaria parasite Plasmodium chabaudi in laboratory mice. We found that
      parasite and particularly host main effects explained most of the variance in
      virulence (anaemia and weight loss), resistance (parasite burden) and
      transmission potential. Host-by-parasite interactions were of limited influence,
      but nevertheless had significant effects. This raises the possibility that host
      heterogeneity may affect the rate of any parasite response to selection on
      virulence. This study of rodent malaria is one of the first tests for host-by
      parasite interactions in any vertebrate disease; host-by-parasite interactions
      typical of those assumed in coevolutionary models were present, but were by no
      means pervasive.

PMID- 16910992
TI  - Disassociation between weak sexual isolation and genetic divergence in a
      hermaphroditic land snail and implications about chirality.
AB  - Examination of the association between reproductive isolation and genetic
      divergence in a variety of organisms is essential for elucidating the mechanisms
      causing speciation. However, such studies are lacking for hermaphrodites. We
      measured premating (sexual) isolation in species pairs of the hermaphroditic land
      snail Albinaria and we compared it with their genetic divergence. We did not find
      substantial sexual isolation barriers between the species studied. The absence of
      strong sexual isolation between species implies its minor effect in the evolution
      of this genus, because distributional, population and life-history
      characteristics of Albinaria make mate-choice possibly redundant. Furthermore, we
      found disassociation between genetic divergence and sexual isolation, suggesting
      that they do not form necessarily a cause-effect duet. However, Albinaria
      voithii, the only dextral Albinaria species, shows strong sexual isolation
      against the other sinistral species. We discuss whether change in coiling either
      has triggered instantaneous speciation, or is an example of character
      displacement.

PMID- 16910993
TI  - Genetic mating patterns studied in pools with manipulated nest site availability
      in two populations of Pomatoschistus minutus.
AB  - Pomatoschistus minutus show paternal care in a resource defence mating system. We
      investigated the effect of nest-site availability on parasitic spawning. Each
      experimental pool contained four potentially nest-building males, four females
      and nests-sites in shortage (2) or excess (6). Both treatments were conducted in
      two populations; one with natural nest-sites in excess, one with a nest-site
      shortage. Microsatellite-DNA revealed that all nest-holders had fertilized most
      of the eggs they tended. Yet, 35% of the nests contained eggs fertilized by
      another male and 14.4% of the males had performed parasitic spawning. There was
      no site or treatment effect. Several females spawned in two nests, which
      coincided with parasitic spawnings, suggesting a cost to the nest-holder in terms
      of lost mating success. Nest-holders with and without eggs and non-nesting males
      all spawned parasitically, generating a significantly lower opportunity for
      sexual selection compared to if there had been no parasitic spawning.

PMID- 16910994
TI  - Replicated population divergence caused by localized coevolution? A test of three
      hypotheses in the red crossbill-lodgepole pine system.
AB  - Several lines of evidence support the hypothesis that local populations of red
      crossbills (Loxia curvirostra complex) enter into a predator-prey arms race with
      lodgepole pine (Pinus contorta latifolia) in the absence of competing pine
      squirrels (Tamiasciurus hudsonicus). Nevertheless, the alternative hypotheses
      that neutral evolution or factors other than squirrels have caused crossbill
      population differentiation have not been thoroughly tested. We compared crossbill
      and pine cone morphology between island populations where squirrels are absent or
      present, and mainland sites where squirrels are present, in order to distinguish
      among these hypotheses. All comparisons supported an effect of squirrel absence,
      not island status, on crossbill and cone morphology. Hence our results provide
      further evidence that strong localized coevolutionary interactions in a
      geographic mosaic have driven adaptive population differentiation. In addition,
      vocal differentiation of crossbills was related to the absence of squirrels, but
      not to island status. As morphological and vocal differentiation is correlated
      with reproductive isolation in crossbills, the geographic mosaic of coevolution
      also seems to promote ecological speciation.

PMID- 16910995
TI  - Spermicide, cryptic female choice and the evolution of sperm form and function.
AB  - Sperm competition and cryptic female choice profoundly affect sperm morphology,
      producing diversity within both species and individuals. One type of within
      individual sperm variation is sperm heteromorphism, in which each male produces
      two or more distinct types of sperm simultaneously, only one of which is
      typically fertile (the "eusperm"). The adaptive significance of nonfertile
      "parasperm" types is poorly understood, although numerous sperm-heteromorphic
      species are known from many disparate taxa. This paper examines in detail two
      female-centred hypotheses for the evolution and maintenance of this
      unconventional sperm production strategy. First, we use game theoretical models
      to establish that parasperm may function to protect eusperm from female-generated
      spermicide, and to elucidate the predictions of this idea. Second, we expand on
      the relatively undeveloped idea that parasperm are used by females as a criterion
      for cryptic female choice, and discuss the predictions generated by this idea
      compared to other hypotheses proposed to explain sperm heteromorphism. We
      critically evaluate both hypotheses, suggest ways in which they could be tested,
      and propose taxa in which they could be important.

PMID- 16910996
TI  - Low abundance of Escherichia coli microsatellites is associated with an extremely
      low mutation rate.
AB  - It is widely assumed that microsatellites are generated by replication slippage,
      a mutation process specific to repetitive DNA. Consistent with their high
      mutation rate, microsatellites are highly abundant in most eukaryotic genomes. In
      Escherichia coli, however, microsatellites are rare and short despite the fact
      that a high microsatellite mutation rate was described. We show that this high
      microsatellite instability depends on the presence of the F-plasmid. E. coli
      cells lacking the F-plasmid have extremely low microsatellite mutation rates.
      This result provides a possible explanation for the genome-wide low density of
      microsatellites in E. coli. Furthermore, we show that the F-plasmid induced
      microsatellite instability is independent of the mismatch repair pathway.

PMID- 16910997
TI  - Evolution of larval host plant associations and adaptive radiation in pierid
      butterflies.
AB  - Butterflies in the family Pieridae (Lepidoptera: Papilionoidea) feed as larvae on
      plants belonging primarily to three distantly related angiosperm orders: Fabales
      (legumes and allied plants), Brassicales (crucifers and related plants containing
      mustard oil glucosides), and Santalales ('mistletoes'). However, some utilize
      plants from 13 other families in a further eight orders. We investigated the
      evolutionary history of host plant use of the Pieridae in the context of a recent
      phylogenetic hypothesis of the family, using simple character optimization.
      Although there is a close association between host plant and butterfly higher
      classification, we find no evidence for cospeciation but a pattern of repeated
      colonization and specialization. The ancestral host of the family appears to be
      Fabaceae or Fabales, with multiple independent shifts to other orders, including
      three to Santalales. The shift to Brassicales, which contain secondary compounds
      (glucosinolates), promoted diversification and adaptive radiation within the
      subfamily Pierinae. Subsequent shifts from crucifers to mistletoes (aerial-stem
      hemiparasites) facilitated further diversification, and more recent shifts from
      mistletoes to mistletoe host trees led to exploitation of novel host plants
      outside the conventional three orders. Possible mechanisms underlying these host
      shifts are briefly discussed. In the Pierinae, a striking association between
      host plant, larval and adult behaviour, adult phenotype, and mimicry calls for
      further research into possible relationships between host specialization, plant
      chemistry and butterfly palatability.

PMID- 16910998
TI  - Microsatellite variation among diverging populations of Drosophila mojavensis.
AB  - Divergence and speciation may occur by various means, depending on the particular
      history, selective environments, and genetic composition of populations. In
      Drosophila mojavensis, a good model of incipient speciation, understanding the
      population genetic structure within this group facilitates our ability to
      understand the context in which reproductive isolation among populations is
      developing. Here we report the genetic structure and relationships of D.
      mojavensis populations at nuclear loci. We surveyed 29 populations throughout the
      distribution of D. mojavensis for four microsatellite loci to differentiation
      among populations of this species. These loci reveal four distinct geographical
      regions of D. mojavensis populations in the south-western United States and north
      western Mexico--(i) Baja California peninsula (Baja), (ii) Sonora, Mexico
      southern Arizona, United States (Sonora), (iii) Mojave Desert and Grand Canyon
      (Mojave), and (iv) Santa Catalina Island (Catalina). While all regions show
      strong isolation, Mojave and Catalina are highly diverged from other regions.
      Within any region, populations are largely homogenous over broad geographical
      distances. Based on the population structure, we find clear geographical barriers
      to gene flow appear to have a strong effect in isolating populations across
      regions for this species.

PMID- 16910999
TI  - Genetic and environmental variation in immune response of collared flycatcher
      nestlings.
AB  - This paper aims at partitioning genetic and environmental contribution to the
      phenotypic variance in nestling immune function measured with the
      hypersensitivity test after inoculation with phytohaemagglutinin. A cross
      fostering experiment with artificial enlargement of some broods was conducted.
      Variation in nestling immune response was related to their common origin, which
      suggests heritable component of cell-mediated immunity. A common rearing
      environment also explained a significant part of variation. However,
      deterioration of rearing conditions as simulated by enlargement of brood size did
      not affect nestling immunocompetence, although it affected nestling body mass.
      Variation in body mass explained some of the variation in immune response related
      to rearing environment, which means that growth is more sensitive to the shifts
      in rearing conditions than the development of immune function. Heritable
      variation in immune response suggests that there should be potential for
      selection to operate and the micro evolutionary changes in immunity of flycatcher
      nestlings are possible.

PMID- 16911000
TI  - Demography, altruism, and the benefits of budding.
AB  - It is now widely appreciated that competition between kin inhibits the evolution
      of altruism. In standard population genetics models, it is difficult for
      indiscriminate altruism towards social partners to be favoured at all. The reason
      is that while limited dispersal increases the kinship of social partners it also
      intensifies local competition. One solution that has received very little
      attention is if individuals disperse as groups (budding dispersal), as this
      relaxes local competition without reducing kinship. Budding behaviour is
      widespread through all levels of biological organization, from early
      protocellular life to cooperatively breeding vertebrates. We model the effects of
      individual dispersal, budding dispersal, soft selection and hard selection to
      examine the conditions under which altruism is favoured. More generally, we
      examine how these various demographic details feed into relatedness and scale of
      competition parameters that can be included into Hamilton's rule.

PMID- 16911001
TI  - Alveolata histone-like proteins have different evolutionary origins.
AB  - Prokaryotic histone-like proteins (Hlps) are abundant proteins found in bacterial
      and plastid nucleoids. Hlps are also found in the eukaryotic dinoflagellates and
      the apicomplexans, two major lineages of the Alveolata. It may be expected that
      Hlps of both groups were derived from the same ancestral Alveolates. However, our
      phylogenetic analyses suggest different origins for the dinoflagellate and the
      apicomplexan Hlps. The apicomplexan Hlps are affiliated with the cyanobacteria
      and probably originated from Hlps of the plastid genome. The dinoflagellate Hlps
      and the proteobacterial long Hlps form a clade that branch off from the node with
      the proteobacterial short Hlps.

PMID- 16911002
TI  - Sexual reproduction advances autumn leaf colours in mountain birch (Betula
      pubescens ssp. czerepanovii).
AB  - Autumnal change in leaf colour of deciduous trees is one of the most fascinating
      displays in nature. Current theories suggest that autumn leaf colours are
      adaptations to environmental stress. Here I report that the number of ripening
      female catkins altered timing of yellow autumn leaf colours in mountain birch.
      The tree's autumnal colour change was brought forward if the tree matured plenty
      of female catkins. Since yellow colour pigments in leaves are unmasked as leaf
      nitrogen is re-translocated, sexual reproduction may alter resource allocation at
      times of leaf senescence. Thus, our current view on the reasons for leaf
      senescence has to be re-examined, and a novel evolutionary explanation is needed
      for the appearance of yellow autumn leaf colours.

PMID- 16911004
TI  - Strategies to diminish the danger of cerebral edema in a pediatric patient
      presenting with diabetic ketoacidosis.

PMID- 16911005
TI  - Continuous non-invasive end-tidal CO2 monitoring in pediatric inpatients with
      diabetic ketoacidosis.
AB  - INTRODUCTION: Pediatric inpatients with diabetic ketoacidosis (DKA) are routinely
      subjected to frequent blood draws in order to closely monitor degree of acidosis
      and response to therapy. The typical level of acidosis monitoring is less than
      ideal, however, because of the high cost and invasiveness of frequent blood labs.
      Previous studies have validated end-tidal carbon dioxide (EtCO2) monitoring in
      the emergency department (ED) for varying periods of time. We extend these
      findings to the inpatient portion of the hospitalization during which the
      majority of blood tests are sent. METHODS: All patients admitted to an
      intermediate care unit in (InCU) a large children's hospital were fitted with an
      appropriately sized oral/nasal cannula capable of sensing EtCO2. Laboratory
      studies were obtained according to hospital clinical practice guidelines. In a
      retrospective analysis, EtCO2 values were correlated with serum total CO2
      (stCO2), venous pH (vpH), venous pCO2 (vpCO2), and calculated bicarbonate from
      venous blood gas (vHCO3-). RESULTS: A total of 78 consecutive episodes of DKA in
      72 patients aged 1-21 yr were monitored for 3-38 h with both capnography and
      laboratory testing, producing 334 comparisons. Initial values were as follows,
      reported as median (range): stCO2, 11 (4-22) mmol/L; vpH, 7.281 (6.998-7.441);
      vpCO2, 28.85 (9.3-43.3) mmHg; and vHCO3-, 14 (3-25) mmol/L. EtCO2 was correlated
      well with stCO2 (r = 0.84, p < 0.001), vHCO3- (r = 0.84, p < 0.001), and vpCO2 (r
      = 0.79, p < 0.001). CONCLUSIONS: These data support the findings of previous
      studies limited to ED populations and suggest that non-invasive EtCO2 monitoring
      is a valuable and reliable tool to continuously follow acidosis in the setting of
      the acutely ill pediatric patient with DKA. Continuous EtCO2 monitoring offers
      the practitioner an early warning system for unexpected changes in acidosis that
      augments the utility of intermittent blood gas determinations.

PMID- 16911006
TI  - Do mothers of overweight Argentinean preschool children perceive them as such?
AB  - Childhood overweight is rapidly on the rise and underlies the younger
      presentation of diabetes. The aim of this study was to determine the association
      between overweight and age, sex, and the perception of the overweight children by
      their mothers. Three hundred and twenty-one (160 males) children (mean age 4.39
      +/- SD 0.83 yr) [body mass index (BMI) 16.6 +/- 2.11] from schools at the
      kindergarten level were evaluated. Data on age, sex, weight, and height were
      recorded. At risk for overweight and overweight were defined as a BMI of > or =
      85th or > or = 95th percentile, respectively. Written questionnaires for mothers'
      perceptions about their children's eating habits (a lot, right, little, or very
      little) and shape (very fat, fat, normal, and thin) were performed. The
      prevalence of at risk of overweight and overweight was 19 and 18.4%,
      respectively. There was a significant difference in the proportion of distorted
      perception of shape between mothers of normal-weight children vs. those of at
      risk of overweight and overweight children (17 vs. 87.5%, p < 0.001). Seventy-six
      and 98% of mothers of overweight and at risk of overweight children,
      respectively, rated them as normal or thin. Mothers exhibited poor overall
      ability to estimate the way at risk of overweight and overweight children ate.
      There was a significant difference in the proportion of distorted perception of
      eating habits between mothers of normal-weight children vs. those of at risk of
      overweight and overweight children (36.3 vs. 90.8%, p < 0.001). Eighty-four and
      96% of mothers of obese and overweight children, respectively, thought that their
      children ate right or little. A multiple regression analysis using BMI > 95th
      percentile as the dependent variable showed that the mothers' perceptions of
      shape and eating habits [odds ratio 4.5; 95% confidence interval (CI) 2.5-7.8; p
      < 0.0001] were both significant independent risk factors for overweight, adjusted
      for age and sex. The agreement between the perception of shape and eating habits
      vs. the medical records BMI > 95th percentile was poor; for shape: kappa 0.31 +
      0.07; 95% CI 0.17-0.44, and for nutrition: 0.14 + 0.06; 95% CI 0.02-0.27. This
      suggests that the mothers' perceptions of shape and eating behavior is a
      predictor of obesity and could be used in clinical practice as a simple tool to
      identify children at high risk for overweight.

PMID- 16911007
TI  - Elevated fasting triglycerides predict impaired glucose tolerance in adolescents
      at risk for type 2 diabetes.
AB  - OBJECTIVE: The aim of this study was to evaluate whether fasting laboratory
      values can predict impaired glucose tolerance (IGT) in adolescents who are at
      risk for developing type 2 diabetes mellitus (T2DM). HYPOTHESIS: Elevated fasting
      triglycerides, a marker for worsening insulin resistance, predict risk for IGT.
      DESIGN: Following a fast of at least 9 h, laboratory measures, body mass index
      (BMI), and demographic information were obtained. The subjects then underwent a
      75-g oral glucose challenge with a 2-h postchallenge glucose determination.
      SUBJECTS: Eighty-four adolescents aged 12-20 yr with at least two risk factors
      for developing T2DM (obesity, family history of T2DM, or acanthosis nigricans)
      and with either a fasting insulin level > or =25 microU/mL or a homeostasis model
      assessment of insulin resistance (HOMA-IR) > or =3.5 were recruited for the
      study. RESULTS: Ten subjects (12%) had IGT [2-h glucose > or =140 mg/dL (7.77
      mmol/L)], and 10 subjects (12%) had impaired fasting glucose [IFG; fasting
      glucose > or =100 mg/dL (5.55 mmol/L)]. However, only three (30%) subjects with
      IGT had IFG, though all subjects with IGT had a fasting triglyceride level > or
      =150 mg/dL (1.70 mmol/L). Of those subjects with elevated triglycerides, 29% had
      IGT. As a screening test to predict risk for IGT, elevated triglycerides >150
      mg/dL had a sensitivity of 100% and a specificity of 68%. The positive predictive
      value was 29%, and the negative predictive value was 100%. CONCLUSIONS: Screening
      with fasting glucose alone would have missed 70% of subjects with IGT in this
      population of insulin-resistant adolescents. However, a fasting triglyceride
      level > or =150 mg/dL was strongly associated with IGT and may help to identify
      at-risk adolescents who should undergo formal glucose tolerance testing.

PMID- 16911008
TI  - Does lean rather than fat mass provide the link between birth weight, BMI, and
      metabolic risk? EarlyBird 23.
AB  - BACKGROUND: High birth weight predicts subsequent obesity, but paradoxically, a
      reduced risk of subsequent cardiovascular disease compared with low birth weight.
      This apparent paradox might be explained if high birth weight programmed a
      greater proportion of subsequent lean mass, which carries less cardiovascular
      risk than fat tissue. AIM: The aim of this study was to test the hypothesis that
      the direct correlation between birth weight and subsequent body mass index (BMI)
      represents an association between birth weight and lean tissue, and to assess the
      metabolic impact of this relationship. METHODS: A total of 234 healthy
      prepubertal children (133 boys, 101 girls, mean age 5.9 yr +/- 0.3 standard
      deviation) were studied. Birth weights were obtained from maternity records. Lean
      mass was measured by bioelectrical impedance. Anthropometric measures included
      height, weight (BMI), waist circumference, and subcutaneous fat mass (FM).
      Insulin resistance was assessed by the homeostasis model method. Metabolic
      correlates of insulin resistance included total and high-density lipoprotein
      cholesterol, triglycerides, and sex-hormone-binding globulin. RESULTS: Birth
      weight correlated significantly with lean mass in boys (r = 0.41, p < 0.001) and
      girls (r = 0.27, p < 0.01). Adjusting for BMI did not improve the correlation
      further. After adjustment for FM, lean mass correlated inversely with
      triglycerides in boys only (r = -0.41, p < 0.01). Birth weight correlated
      inversely with triglycerides in boys (r = -0.18, p < 0.05); after adjustment for
      lean mass, this correlation was not significant. INTERPRETATION: In boys, the
      relationships between birth weight, triglycerides, and lean mass are consistent
      with the hypothesis. Overall, our findings provide limited evidence in support of
      the argument that higher birth weight predicts lower metabolic risk because it
      marks programming of more lean mass.

PMID- 16911009
TI  - Predictors of fear of hypoglycemia in adolescents with type 1 diabetes and their
      parents.
AB  - OBJECTIVES: This study tested the hypothesis that both trait anxiety and
      hypoglycemic history contribute to fear of hypoglycemia (FOH) both in adolescents
      with type 1 diabetes mellitus (T1DM) and in their parents, and relationships
      between FOH and other variables including metabolic control, symptom perception,
      and use of insulin pump therapy. STUDY DESIGN: Thirty-nine parent-adolescent
      pairs completed questionnaires assessing background and clinical information,
      hypoglycemic episodes, FOH, and trait anxiety. Adolescent blood was also sampled
      for glycosylated hemoglobin A1c (HbA1c) measurement. RESULTS: In adolescents,
      both trait anxiety and frequency of severe hypoglycemic episodes were significant
      predictors of FOH, together accounting for almost 50% of the variance. Parental
      FOH was not predicted by their own trait anxiety or their child's hypoglycemic
      history but by whether they believed that their child carried emergency glucose.
      FOH was not related to metabolic control, although adolescents who experienced
      recent severe hypoglycemia (SH) with unconsciousness had significantly higher
      HbA1c. Parental trait anxiety significantly correlated with child trait anxiety,
      but parent-child levels of FOH were unrelated. Neither trait anxiety nor FOH
      related to reported symptoms, and FOH was not lower in parents with insulin pump
      therapy. CONCLUSIONS: Consistent with findings from adult patient populations,
      trait anxiety levels and recent experiences with hypoglycemia predict FOH in
      adolescents with T1DM. In parents, however, beliefs about their adolescents'
      ability to cope with hypoglycemic episodes predicted FOH. FOH in adolescents with
      T1DM and their parents is a complex construct influenced by multiple personality
      and situational and behavioral factors, and its impact on diabetes management
      remains unclear.

PMID- 16911010
TI  - Blood ketone bodies in patients with recent-onset type 1 diabetes (a multicenter
      study).
AB  - BACKGROUND: Insulin deficiency with glucagon excess leads to the release of
      ketone bodies (KBs) by the liver and excretion in the urine. So far, only KB
      monitoring in urine has been used during assessment of children with diabetes.
      Currently used nitroprusside strips for urine KB detection react only with
      acetoacetate (AcAc) and not with the most prevalent KB moiety - 3beta
      hydroxybutyrate (3HB) - that is in equilibrium with AcAc (up to 10:1 ratio). AIM:
      To verify the significance of 3HB in the blood compared to that of AcAc in the
      urine in recently diagnosed type 1 diabetic subjects independent of the presence
      of diabetic ketoacidosis (DKA). METHODS: A total of 118 consecutive newly
      diagnosed subjects with type 1 diabetes from different centers in Italy underwent
      intensive insulin therapy and hydration when necessary (38/118 = 32% with DKA).
      Hourly urine and capillary blood samples were used to monitor KBs until metabolic
      control was achieved. RESULTS: Although DKA was present in 32% of patients, blood
      3HB was significantly increased (3.56 +/- 1.7 mmol/L) in 83% of the patients and
      correlated with blood glucose (r = 0.39; p < 0.01) according to a bimodal model.
      The strongest association was found between 3HB and venous pH (r =-0.56; p <
      0.0001). Time required for blood 3HB normalization depended strongly on the
      starting blood KB values (r = 0.44; p < 0.0001) and was significantly lower than
      that required for disappearance of KB from urine (17.4 +/- 13.6 h, range 1-69 h
      vs. 19.7 +/- 17.8 h, range 1-120 h; p = 0.004). However, urine KBs disappeared
      before blood 3HB normalization in 23% of the patients. CONCLUSIONS: Blood 3HB
      evaluation is a better indicator of metabolic control compared to urine KB
      detection and is useful to predict the time required for blood KB clearing.
      Further studies are needed to assess its use in the early detection and
      management of DKA.

PMID- 16911011
TI  - Arterial thrombosis resulting in amputation in a child with poorly controlled
      type 1 diabetes and heterozygous Factor V Leiden mutation.
AB  - Children with venous thromboses have greater than 50% likelihood of carrying a
      genetic thrombophilic defect, and two-thirds of such defects will be a mutation
      in the factor V gene referred to as Factor V Leiden. Poorly controlled type 1
      diabetes mellitus (T1DM) increases the risk for thrombosis. We report a massive
      arterial thrombosis resulting in unilateral below-the-knee amputation in a 12-yr
      old white girl with a heterozygous Factor V Leiden mutation and a 2-yr history of
      poorly controlled T1DM. This report emphasizes the need to test for thrombophilic
      defects in children with thrombosis or with a family history of thrombosis. Good
      metabolic control is especially important in children with T1DM and known
      thrombophilic defects.

PMID- 16911014
TI  - Adverse perinatal conditions in hearing-impaired children in a developing
      country.
AB  - Prevailing adverse perinatal conditions in developing countries have been
      associated with substantial mortality, but little evidence exists on their impact
      on permanent childhood disabilities and morbidity due to limitations in clinical
      investigations and medical records. This study aims to identify the possible
      association between parent-reported adverse perinatal conditions and permanent
      hearing loss, in order to establish service needs within current maternal and
      child health programmes. Structured questionnaires were administered to 363
      parents of deaf children and 309 parents of normal-hearing children in an inner
      city area of Lagos, Nigeria. The parents were from all social classes. After a
      multivariable logistic regression analysis, birth asphyxia [OR 20.45; 95% CI
      6.26, 66.85], difficult delivery [OR 8.09; 95% CI 2.76, 23.68], neonatal jaundice
      [OR 2.45; 95% CI 1.25, 4.79] and neonatal seizures [OR 2.30; 95% CI 1.09, 4.85]
      were associated with permanent hearing loss. Consanguineous marriages [OR 6.69;
      95% CI 2.72, 16.46] and family history of deafness [OR 6.27; 95% CI 2.07, 18.97]
      also emerged as additional risk factors for permanent hearing loss. In addition,
      parents of children in state-owned schools for the deaf were significantly more
      likely to belong to higher social classes compared with normal-hearing children
      in mainstream state-owned schools. There is a need to incorporate services for
      the early detection of permanent hearing loss into current maternal and child
      healthcare programmes in developing countries.

PMID- 16911015
TI  - Consanguineous unions and child health in the State of Qatar.
AB  - The aim of the study was to estimate the prevalence and sociodemographic
      predictors of consanguineous unions in the State of Qatar and to assess the
      association between consanguinity, fertility and child health. A representative
      sample of 1800 Qatari women aged > or =15 years was approached for the study. Of
      these, 1515 (84.2%) women agreed to participate. The consanguineous marriage rate
      was 54.0% with estimated population confidence limits of 52.3-55.7%. First cousin
      unions were the most common form of cousin marriage. The level of parental
      consanguinity (both in the respondent's parents and her parents-in-law) was quite
      high. In a multivariable analysis, both education of the respondent and her
      husband as well as parental consanguinity were found to be strong predictors of
      consanguineous unions in the index generation. Although fertility was high in
      both groups, the mean number of pregnancies was somewhat higher in respondents
      with first cousin unions. Concomitantly they also had a slighter higher rate of
      livebirths than women in non-consanguineous unions. The occurrence of asthma,
      mental retardation, epilepsy and diabetes was significantly more common in
      offspring of all consanguineous than non-consanguineous couples.

PMID- 16911016
TI  - Risk factors for subclinical mastitis among HIV-infected and uninfected women in
      Lusaka, Zambia.
AB  - Subclinical mastitis, defined as raised milk sodium/potassium (Na/K) ratio, is
      associated with poor infant growth and, among HIV-infected women, with increased
      milk HIV viral load. We conducted a longitudinal cohort study in Lusaka, Zambia,
      in order to investigate the relative importance of several potential causes of
      subclinical mastitis: maternal infection, micronutrient deficiencies and poor
      lactation practice. Women (198 HIV-infected, 189 HIV-uninfected) were recruited
      at 34 weeks' gestation and followed up to 16 weeks postpartum for collection of
      information on their health, their infant's health, infant growth and infant
      feeding practices. Milk samples were collected from each breast at 11 postpartum
      visits and blood at recruitment and 6 weeks postpartum. The geometric mean milk
      Na/K ratio and the proportion of women with Na/K ratio > 1.0 in one or both
      breasts were significantly higher among HIV-infected than among uninfected women.
      Other factors associated with the higher mean Na/K ratio in univariable analyses
      were primiparity, high maternal alpha(1)-acid glycoprotein (AGP) at 6 weeks,
      maternal overall morbidity and specific breast symptoms, preterm delivery, low
      infant weight or length, infant thrush and non-exclusive breast feeding. In
      multivariable analyses, primiparity, preterm delivery, breast symptoms, HIV
      status and raised AGP were associated with the raised Na/K ratio. Thus the main
      factors associated with subclinical mastitis that are amenable to intervention
      are poor maternal overall health and breast health. The impact of improved
      postpartum health care, especially management of maternal infections and
      especially in primiparous women, on the prevalence of subclinical mastitis and
      its consequences requires investigation.

PMID- 16911017
TI  - Risk factors for hospital admission related to excessive and/or prolonged
      postpartum vaginal blood loss after the first 24 h following childbirth.
AB  - A population case-control study was used to determine risk factors for excessive
      and/or prolonged vaginal bleeding (described collectively as vaginal loss
      problems) and uterine infection from 24 h to 3 months postpartum. Data were
      obtained from women whose maternity care took place in one of two health
      districts in the south of England. The cases were women remaining in or admitted
      to hospital with excessive or prolonged vaginal blood loss from 24 h to 3 months
      postpartum. Two controls for each case were identified; these were women whose
      delivery was the nearest in time and in the same location as the case delivery.
      Medical and midwifery records were searched retrospectively to cover hospital
      admissions for vaginal blood loss problems or uterine infection in postpartum
      women from 1 January 1994 to 31 December 1995. Data were analysed for 243 cases
      and 486 controls. Univariable analysis identified 28 variables associated with
      being a case. Using multivariable analysis, nine factors remained in the final
      model, with a history of secondary postpartum haemorrhage (PPH) being the most
      strongly predictive (OR [95% confidence interval] 6.0 [2.1, 16.8]). Vaginal
      bleeding prior to 24 weeks' gestation (OR 3.0 [1.6, 5.9]), third trimester
      hospital admission (OR 2.0 [1.4, 2.8]), maternal smoking (OR 2.7 [1.8, 3.9]), a
      prolonged (OR 3.1 [1.2, 7.5]) or incomplete third stage (OR 2.1 [1.0, 4.4]), and
      primary PPH (OR 4.7 [1.9, 11.6]) for blood loss >500 mL, were predictive of
      becoming a case. No significant association was identified for parity (OR 1.1
      [0.8, 1.5]) or method of delivery, spontaneous (OR 1.0 [0.7, 1.3]), instrumental
      (OR 1.4 [0.9, 2.2]) or operative (OR 1.2 [0.8, 1.9]). This is a neglected area of
      women's health after childbirth, and the value of this study is in the
      identification of potential risk factors for postpartum morbidity related to
      vaginal blood loss. Where morbidity occurs, early diagnosis, management and
      treatment are likely to reduce its extent or duration. It is considered that
      raising awareness about these factors, both among healthcare professionals and
      women themselves, may play an important part in the recognition and treatment of
      postpartum morbidity.

PMID- 16911019
TI  - Child health and the environment: the INMA Spanish Study.
AB  - The INMA (INfancia y Medio Ambiente [Environment and Childhood]) is a population
      based cohort study in different Spanish cities, that focuses on prenatal
      environmental exposures and growth, development and health from early fetal life
      until childhood. The study focuses on five primary areas of research: (1) growth
      and physical development; (2) behavioural and cognitive development; (3) asthma
      and allergies; (4) sexual and reproductive development; and (5) environmental
      exposure pathways. The general aims of the project are: (1) to describe the
      degree of individual prenatal exposure to environmental pollutants, and the
      internal dose of chemicals during pregnancy, at birth and during childhood in
      Spain; (2) to evaluate the impact of the exposure to different contaminants on
      fetal and infant growth, health and development; (3) to evaluate the role of diet
      on fetal and infant growth, health and development; and (4) to evaluate the
      interaction between persistent pollutants, nutrients and genetic determinants on
      fetal and infant growth, health and development. Extensive assessments will be
      carried out on 3100 pregnant women and children. Data will be collected by
      physical examinations, questionnaires, interviews, ultrasound and biological
      samples. Pregnant women are being assessed at 12, 20 and 32 weeks of gestation to
      collect information about environmental exposures and fetal growth. The children
      will be followed until the age of 4 years.

PMID- 16911020
TI  - APIKIDS: a cohort of children born after assisted reproductive technologies.
AB  - A cohort of children born after assisted reproductive technologies (ART) was set
      up in 2003 in Italy. It aims to follow up the children in order to study the
      short- and long-term effects of ART. Parents who agreed to participate were
      contacted for a telephone interview; questions included occupational and non
      occupational exposure to carcinogens, reproductive history, history of index
      pregnancy (including drugs used during pregnancy), delivery and the child's
      health status. By August 2005, 40 out of the 50 centres contacted (80%) had
      agreed to participate in the study, and 17 had already sent their data.
      Information on a total of 2451 cycles ending with a pregnancy are currently
      available, from 2245 couples. We have contacted 351 of these couples (16%), 309
      of whom (88% of the contacts) agreed to participate in the study and were
      interviewed, while 36 (11%) refused to be interviewed. The total number of
      children currently included in the database is 411. This study is the first
      attempt to create a database containing information on children born after ART in
      Italy. It will provide results on both short- and long-term outcomes in these
      children.

PMID- 16911021
TI  - Collecting population-based perinatal data efficiently: the example of the
      Lebanese National Perinatal Survey.
AB  - We describe the methodology and the main results of the Lebanese perinatal health
      survey. The survey was carried out during two consecutive weeks in autumn 1999
      and spring 2000, with the aim of obtaining a minimum data set on all births
      occurring during a short period of time. All live births and stillbirths
      occurring during these periods in medical settings were recorded. The sample
      included 5231 women and 5333 newborns. Data were obtained from medical records
      and by interviewing the women in hospital after delivery. All maternity units and
      birth centres agreed to participate. Maternal characteristics, medical care
      during pregnancy and delivery, and pregnancy outcome were similar for the two
      study periods. However, gestational age distribution differed between the two
      periods. In total, 9.0% of infants were born < 37 weeks of gestation and 7.0%
      weighed < 2500 g at birth. Wide regional variations were observed for many
      indicators of health, care and risk factors. For instance, the caesarean section
      rate varied from 16.2% in the North Region to 28.0% in Beirut. The survey
      protocol was successfully applied in Lebanon and may be useful in other countries
      that have a relatively well-developed healthcare system, but few sources of
      reliable population-based statistics on health and medical care. This type of
      survey may also be an appropriate instrument for collecting additional data for
      health policy evaluations.

PMID- 16911022
TI  - Assessing mid-trimester salivary cortisol levels across three consecutive days in
      pregnant women using an at-home collection protocol.
AB  - The Pregnancy Outcomes and Community Health (POUCH) Study enrolled women in their
      15th to 27th week of pregnancy from 52 prenatal clinics located in five
      communities. After the study began, an at-home protocol to measure maternal
      stress was added, which included collection of urine and saliva twice a day
      (waking = AM, bedtime = PM) for three consecutive days, and completion of a daily
      diary. The at-home protocol was in place for 2852 POUCH participants at
      enrollment, and 81.3% (n = 2318) consented and returned samples and diary. For
      these analyses, salivary cortisol was analysed in a subset of 846 women who
      delivered at term. Day-to-day correlation coefficients for AM cortisol (0.45
      0.55) exceeded those for PM cortisol (0.31-0.43). Study diaries indicated that
      there was variation in the time interval between waking and sample collection.
      Analyses of discrete intervals showed the same awakening response pattern in
      cortisol levels that has been reported in studies with serial AM sampling. The
      adjusted mean AM cortisol (microg/dL) was 0.506 at 0-15 min post-waking, 0.544 at
      16-30 min (P < 0.05), 0.582 at 31-60 min (P < 0.01), and 0.515 at >60 min post
      waking. In addition, adjusted mean AM cortisol in samples collected at or before
      9 a.m. was higher than that in samples collected after 9 a.m. (0.564 vs. 0.510
      microg/dL, P < 0.01). Among working women, adjusted mean AM cortisol was higher
      on work days than non-work days (0.564 vs. 0.489 microg/dL, P < 0.01), and in
      multiparae compared with primiparae (0.551 vs. 0.502 microg/dL, P = 0.07). The
      parity effect was not evident in non-working women. The adjusted mean PM cortisol
      significantly increased as week of pregnancy at sampling increased, but was not
      significantly related to time of collection, work day and parity. Factors
      influencing AM and PM cortisol levels in pregnancy appear to differ. In studies
      of AM cortisol levels, it is important to gather data on time of sample
      collection, interval from waking to sample collection, parity and work.

PMID- 16911023
TI  - Interactions between fetal HLA-DQ alleles and maternal smoking influence
      birthweight.
AB  - Maternal smoking during pregnancy inhibits fetal growth, and is a major cause of
      childhood and adult morbidity, including increased risks of cardiovascular
      disease and diabetes. However, the use of birthweight as a proxy for future
      smoking-related morbidity is hindered by its wide variability, suggesting a role
      for other birthweight-modifying factors. We report here, for the first time, that
      interactions between specific fetal HLA-DQA1 and DQB1 alleles and maternal
      smoking can influence birthweight. We compared mean birthweights of a series of
      term, HLA-DQ typed white UK newborns (n = 552) whose mothers had either smoked (n
      = 211) or not smoked (n = 341) during pregnancy. Maternal smoking during
      pregnancy resulted in an average birthweight reduction of 244 g, but the combined
      effects of maternal smoking and fetal DQA1*0101 or DQB1*0501 alleles resulted in
      a 230 and 240 g further reduction in mean birthweight, respectively, resulting
      from interactions between smoking and these DQ types. Other fetal DQ allele
      specific interactions with maternal smoking are suggested by a "protective"
      effect on smoking-associated birthweight reduction in newborns typing for
      DQA1*0201 and DQB1*0201. Our results suggest biological interactions between
      maternal cigarette smoking during pregnancy and specific fetal DQ alleles that
      affect fetal growth. The precise nature of these interactions merits further
      investigation, as knowledge of fetal HLA-DQ type may be useful in refining risk
      estimates of severe fetal growth restriction because of maternal smoking during
      pregnancy.

PMID- 16911024
TI  - Population-based retrieval of newborn dried blood spots for researching
      paediatric cancer susceptibility genes.
AB  - We have demonstrated the feasibility of linking newborn blood spots, population
      based cancer incidence data and birth certificate data. Incident cases of acute
      lymphocytic leukaemia and population-based controls were ascertained. We
      retrieved dried blood spot specimens, isolated and amplified DNA, and assayed the
      cancer susceptibility genes GSTT1 and GSTM1. The double null genotype was over
      represented in the cases, consistent with previous reports based on other
      epidemiological methods. The design avoids issues of participation bias by cases
      and controls and can be used to investigate interactions of susceptibility genes
      and xenobiotics in semi-ecological studies. It can be useful for generating or
      testing hypotheses on associations of other paediatric illness and environmental
      contaminants.

PMID- 16911025
TI  - Duration of sleep and breast cancer risk in a large population-based case-control
      study.
AB  - One important function of sleep may be its contribution to the maintenance of the
      immune system and regulation of the circadian rhythms by melatonin. Researchers
      have speculated that disruption of immune functions involving cortisol levels and
      natural killer cell activity may increase breast cancer risk whereas increased
      melatonin exposure may protect against breast cancer. We conducted a multistate
      population-based case-control study of 4,033 women with invasive breast cancer
      and 5,314 community women without breast cancer in which we inquired about
      women's sleep habits in the recent past and during adult lifetime. Relative to
      women who slept 7.0-7.9 h/night, the multivariate odds ratio for developing
      breast cancer among women who slept an average of 9 h or more per night
      approximately 2 years prior to interview was 1.13 (95% CI 0.93-1.37). The
      multivariate-adjusted odds ratio for the continuous term was 1.06 (95% CI 1.01
      1.11), suggesting a 6% increase in risk for every additional hour of sleep.
      Similar patterns were observed for average lifetime adult sleep duration. We
      found little evidence that sleeping few hours per night was associated with
      breast cancer risk. The results of this study suggest that increasing sleep
      duration is modestly associated with an increased breast cancer risk. In
      contrast, short duration of sleep (<7 h/night) is not substantially associated
      with increased risk. Further research in this area is warranted.

PMID- 16911026
TI  - Learning-dependent changes in sleep spindles and Stage 2 sleep.
AB  - It has become increasingly clear that sleep is necessary for efficient memory
      consolidation. Recently, it has been found that Stage 2 sleep disruption impairs
      procedural memory performance, and that memory performance is correlated with the
      duration of Stage 2 sleep; but the mechanisms involved in synaptic plasticity for
      procedural memory during sleep have not been identified. The present study
      examined the learning-dependent changes in sleep, including Stage 2 sleep
      spindles. Following an intense period of simple motor procedural learning, the
      duration of Stage 2 sleep and spindle density increased. There were no changes
      observed in the duration of any other stage of sleep or in the density of rapid
      eye movements. These findings support the hypothesis that sleep spindles are
      involved in the off-line reprocessing of simple motor procedural memory during
      Stage 2 sleep.

PMID- 16911027
TI  - Sleep in healthy seniors: a diary study of the relation between bedtime and the
      amount of sleep obtained.
AB  - The aim of this study was to determine whether naturally occurring inter
      individual and intra-individual differences in bedtime selection in the elderly
      might be lawfully related to the amount of sleep that is obtained. A total of 128
      seniors (63f, 65m) aged 70-92 years each provided a week of sleep diary data
      yielding a total of 896 subject-nights for analysis. From each subject-night the
      diary was used to derive measures of time in bed (TIB) and total sleep time
      (TST). These measures were used as dependent variables in mixed-effect linear
      models (nights nested within subjects) with the independent variable being
      bedtime for that subject-night, arbitrarily expressed as minutes since 19:00
      hours. Although there were strong inter-individual and intra-individual
      differences, for both genders, bedtime had a statistically significant effect (P
      < 0.001) on both TIB and TST. We observed that later bedtimes were associated
      with less time in bed and less time asleep. On average between 7 and 8 min of
      less TIB and TST were associated with each 10-min delay in bedtime from 19:00
      hours. These results are interpreted in terms of increases in sleep being derived
      from living in a better harmony with an earlier peaking circadian pacemaker
      characteristic of older age, although other possible mechanisms are also
      considered (e.g. age-dependent alterations in phase angle and homeostatic sleep
      need).

PMID- 16911028
TI  - Effects of two nights sleep deprivation and two nights recovery sleep on response
      inhibition.
AB  - This study examined the effects of two nights of total sleep deprivation (TSD)
      and two nights of recovery sleep on response inhibition. Thirty-eight young,
      healthy adults performed a Go-NoGo task at 14 : 00 after: (1) a normal night of
      sleep; (2) each of two consecutive nights of TSD; and (3) each of two consecutive
      nights of recovery sleep; they also performed the task at 05 : 00 during the
      first night of sleep deprivation. We hypothesized that TSD would lead to an
      impaired ability to withhold a response that would be reversed with recovery
      sleep. Subjects did experience a significant increase in false positive responses
      throughout all of TSD, errors of omission (i.e. missed 'go' targets) were not
      significant until after the second night of TSD. Both components (withholding a
      response and automatic responding) of the task returned to baseline levels after
      one night of recovery sleep. These data suggest that individuals experience
      difficulty in withholding an inappropriate response during TSD, even when they
      are able to attend to the incoming stimuli and respond accurately to appropriate
      stimuli.

PMID- 16911029
TI  - Epidemiological aspects of self-reported sleep onset latency in Japanese junior
      high school children.
AB  - The purpose of this study was to investigate the relationships between sleep
      onset latency (SOL) and other sleep-wake patterns and media use habits in
      Japanese schoolchildren. A total of 9,718 junior high school children responded
      (12.8 years) and 9199 questionnaires were used in the present analyses. The
      questionnaire assessed sleep-wake patterns, TV viewing and videogame habits.
      Overall, 72.1% of the subjects reported short SOL (<or=20 min). Long SOL subjects
      (>20 min) were strongly associated with disturbed sleep manifested especially by
      increased risk of night awakenings, decreased sleep depth, and bad sleep in
      general (overall sleep quality). Prolonged SOL was also associated with daytime
      sleepiness, difficulties in falling asleep, bad morning feeling and sleep
      insufficiency. We found a U-shaped relationship between sleep period and SOL.
      Increase in bedtime was accompanied by increased risk of prolonged SOL. The
      impact of ultra-short and ultra-long SOL (<or=5 and >or=40 min) was also
      analysed. Long durations of watching television and playing videogame were
      significantly associated with prolonged SOL. After adjustment for sex, girls
      presented significantly higher risk of prolonged SOL. Body mass index adjustment
      did not reveal any significant results. SOL presents a significant component of
      sleep-wake habits; poor sleep hygiene and insufficient sleep time significantly
      increase SOL. Parents, healthcare practitioners and children themselves should be
      aware of the potentially negative influence of prolonged SOL. Additionally, the
      optimal coherent sleep-wake schedule must be promoted in parallel with the
      limitation on the viewing TV and game practices.

PMID- 16911030
TI  - Self-reported sleep duration in Finnish general population.
AB  - Self-reported short or long sleep duration has been repeatedly found to be
      associated with increased mortality and health risks. However, there is still an
      insufficient amount of detailed knowledge available to characterize the short and
      long sleep duration groups in general population. Consequently, the underlying
      mechanisms potentially explaining the health risks associated with short and long
      sleep duration are unclear. In the present study, the self-reported sleep
      duration in a sample of Finnish general population was studied, and its possible
      associations with such factors as self-perceived health, sociodemographic
      characteristics, lifestyle, sleep difficulties and daytime concomitants were
      analyzed. In particular, an effort was made to define mutually statistically
      independent determinants of sleep duration. In the Finnish Health 2000 Survey, a
      representative sample of 8,028 subjects of 30 years of age or older and a sample
      of 1,894 subjects of 18-29 years of age were invited to take part in the health
      interview and health examination. The participation rate of the study was over
      80%. The most important and statistically-independent determinants of short and
      long sleep duration were gender, physical tiredness, sleep problems, marital
      status, main occupation and physical activity. However, in the multivariable
      model they only accounted for approximately 16% of the variance in sleep duration
      in short and long sleepers, suggesting multiple sources of variance. The present
      study also suggests a dose-response like relationship between the sleep duration
      and many of its determinants within both short and long sleepers. A more detailed
      analysis of the clinical status of the short and long sleep duration groups is
      needed to evaluate the possible importance of these findings for health risks
      associated with sleep duration.

PMID- 16911031
TI  - Frequent lapses of responsiveness during an extended visuomotor tracking task in
      non-sleep-deprived subjects.
AB  - We investigated the occurrence of lapses of responsiveness (lapses) in 15 non
      sleep-deprived subjects performing a 1D continuous tracking task during normal
      working hours. Tracking behaviour, facial video, and electroencephalogram (EEG)
      were recorded simultaneously during two 1-h sessions. Rate and duration were
      estimated for lapses identified by a tracking flat spot and/or video sleep.
      Fourteen of the 15 subjects had one or more lapses, with an overall rate of 39.3
      +/- 12.9 lapses per hour (mean +/- SE) and a lapse duration of 3.4 +/- 0.5 s. We
      also found that subjects' performance improved towards the end of the 1-h long
      session, even though no external temporal cues were available. Spectral power was
      found to be higher during lapses in the delta, theta, and alpha bands, and lower
      in the beta, gamma, and higher bands, but correlations between changes in EEG
      power and lapses were low. In conclusion, lapses are a frequent phenomenon in
      normal subjects - even when not sleep-deprived - engaged in an extended
      monotonous continuous visuomotor task. This is of particular importance to the
      transport sector in which there is a need to maintain sustained attention for
      extended periods of time and in which lapses can lead to multiple-fatality
      accidents.

PMID- 16911032
TI  - What predicts patients' perceptions of improvement in insomnia?
AB  - Although there has been considerable research into the effectiveness of
      individual cognitive behavioral treatment for chronic insomnia, less is known
      about patients' perceptions of what constitutes actual improvement. This study
      utilized 70 outpatients (mean age = 49.7 years, SD = 12.0) with insomnia who
      completed a 6-week cognitive behavioral group for sleep. Participants completed a
      number of primary (Pittsburgh Sleep Quality Index) and secondary measures (the
      Dysfunctional Beliefs about Sleep Scale, Insomnia Severity Index, Beck Depression
      Inventory, Penn State Worry Questionnaire) at pre- and post-treatment. Perceived
      improvement was measured using the Clinical Global Improvement Scale (CGI).
      Results were analyzed using a combination of Logistic Regression analysis and
      receiver operating curve characteristic analysis (ROC). Results demonstrated that
      sleep quality and sleep duration were the most sensitive primary measures, or
      best predicted perceived improvement, whereas sleep efficiency was the most
      specific primary measure, or best predicted perceived lack of improvement
      (defined as only mild improvement). Of the secondary measures, results showed
      that daytime impairment was the most sensitive predictor of perceived improvement
      and that mood was the most specific predictor of perceived lack of improvement.
      Implications of these findings are that sleep quality, sleep duration, and sleep
      efficiency may offer different types of information and the choice of measure for
      predicting global improvement in insomnia will depend on the needs of the
      researcher/clinician.

PMID- 16911033
TI  - Development of the sleep quality scale.
AB  - Sleep quality affects health and the overall quality of life. As the factors that
      influence sleep quality and their relative importance vary among individuals, a
      self-report method is essential. Although various questionnaires have been used
      to assess sleep quality, few all-inclusive assessment scales have been developed.
      Therefore, the purpose of this study was to develop an instrument for measuring
      sleep quality and to study its validity and reliability. A Sleep Quality Scale
      (SQS) was developed using item analysis and factor analysis on items with content
      validity. SQS, composed of 28 items and six factors, accounted for 62.6% of the
      total variance. The difference of SQS score between insomniacs and normal
      subjects confirmed the construct validity (t = -13.8, P = 0.000). Concurrent
      validity was identified by the significant correlation of SQS with the Pittsburgh
      Sleep Quality Index (r = 0.72, P = 0.000). The Cronbach's alpha coefficient was
      0.92 for internal consistency and the correlation coefficient was 0.81 for test
      retest reliability at a 2-week interval. The developed SQS was therefore
      confirmed to be a valid and reliable instrument for the comprehensive assessment
      of sleep quality.

PMID- 16911034
TI  - Dry mouth upon awakening in obstructive sleep apnea.
AB  - The aim was to assess the significance of dry mouth upon awakening as a symptom
      of obstructive sleep apnea (OSA). The participants were 668 consecutive adults
      referred for polysomnographic evaluation (PSG) because of snoring and suspected
      OSA, and 582 adults who were attending a general health check-up. Data were
      obtained from self-administered questionnaires and PSG evaluation. The
      participants were asked to answer the following question: 'During the last month,
      did you experience waking up in the morning with a dry mouth?'. The response
      scale consisted of five categories: 'never', 'rarely', 'sometimes', often', or
      'almost always'. We classified patients as having dry mouth upon awakening
      complaint only if they reported experiencing the symptom 'almost always'. The
      prevalence of dry mouth upon awakening was twofold higher in patients with OSA
      (31.4%) than in primary snorers (16.4%, P < 0.001), and increased linearly from
      22.4%, to 34.5%, and 40.7% in mild, moderate, and severe OSA respectively (P <
      0.001). The prevalence of dry mouth upon awakening in the control group was 3.2%.
      Logistic regression results indicated that this symptom significantly
      differentiated OSA patients from primary snorers after adjusting for age, BMI,
      gender, hypertension, and other classical OSA symptoms (OR 2.33, 95% CI 1.34
      4.07). Dry mouth upon awakening appears as a significant symptom of OSA. We
      suggest that increased sleep time spent with an open mouth is a likely
      explanation for these findings.

PMID- 16911035
TI  - Night-to-night alterations in sleep apnea type in patients with heart failure.
AB  - In patients with heart failure, apnea type can shift overnight from mainly
      obstructive to mainly central in association with reductions in PCO(2) and
      increases in periodic breathing cycle length, indicative of a fall in cardiac
      output. We hypothesized that the predominant apnea type could also vary from one
      night to another in association with alterations in PCO(2) and cycle length. We
      studied 12 men with heart failure in whom the predominant apnea type changed from
      one night to the next over periods of at least 1 month, and two groups with
      either predominantly obstructive or central sleep apnea (OSA or CSA) in whom
      apnea type remained stable over time. In patients with unstable apnea type (n =
      12, duration between sleep studies 9.0 +/- 4.4 months), PCO(2) was significantly
      lower (37.6 +/- 1.6 mmHg versus 41.7 +/- 1.9 mmHg, P < 0.01), and cycle length
      significantly longer (61.9 +/- 3.4 s versus 51.0 +/- 1.9 s, P < 0.001) during
      nights with predominantly central than nights with predominantly obstructive
      apnea. In contrast, in both the stable central (n = 8, duration between sleep
      studies 11.9 +/- 5.3 months) and the stable obstructive (n = 8, duration between
      studies 6.9 +/- 5.2 months) sleep apnea groups, neither PCO(2) nor cycle length
      changed significantly between the baseline and follow-up sleep studies. We
      conclude that in some patients with heart failure, OSA and CSA are part of a
      spectrum of periodic breathing that can shift over time in association with
      alterations in PCO(2), cycle length and probably cardiac function.

PMID- 16911036
TI  - Cognitive deficits in narcolepsy.
AB  - The aim of the investigations was to explore the nature and the severity of
      cognitive deficits in narcolepsy patients. In two studies, narcolepsy patients
      were compared with matched control subjects on a range of attention, memory and
      executive control tasks. Impairments were only observed on attention and
      executive function tasks which involved higher demands on inhibition or task
      management abilities whereas relatively routine memory and attention tasks
      yielded intact performance in narcolepsy patients. The overall pattern of results
      indicates an executive control deficit in narcolepsy which might be related to a
      reduction of available cognitive processing resources because of the need for
      continuous allocation of resources to monitoring and maintenance of vigilance.

PMID- 16911037
TI  - Sleep bruxism is associated to micro-arousals and an increase in cardiac
      sympathetic activity.
AB  - Sleep bruxism (SB) subjects show a higher incidence of rhythmic masticatory
      muscle activity (RMMA) than control subjects. RMMA is associated with sleep micro
      arousals. This study aims to: (i) assess RMMA/SB episodes in relation to sleep
      cycles; (ii) establish if RMMA/SB and micro-arousals occur in relation to the
      slow wave activity (SWA) dynamics; (iii) analyze the association between RMMA/SB
      and autonomic cardiac activity across sleep cycles. Two nights of polygraphic
      recordings were made in three study groups (20 subjects each): moderate to high
      SB, low SB and control. RMMA episodes were considered to occur in clusters when
      several groups of RMMA or non-specific oromotor episodes were separated by less
      than 100 s. Correlations between sleep, RMMA/SB index and heart rate variability
      variables were assessed for the first four sleep cycles of each study group.
      Statistical analyses were done with SYSTAT and SPSS. It was observed that 75.8%
      of all RMMA/SB episodes occurred in clusters. Micro-arousal and SB indexes were
      highest during sleep cycles 2 and 3 (P < 0.001). Within each cycle, micro-arousal
      and RMMA/SB indexes showed an increase before each REM sleep (P <or= 0.02). The
      cross-correlation plot for micro-arousal index showed positive association from 4
      min preceding SB onset in the moderate to high SB subjects (P <or= 0.06). The
      cross-correlation plot revealed that SWA decreases following SB onset (P <or=
      0.05). Further cross-correlation analysis revealed that a shift in sympatho-vagal
      balance towards increased sympathetic activity started 8 min preceding SB onset
      (P <or= 0.03). In moderate to severe SB subjects, a clear increase in sympathetic
      activity precedes SB onset.

PMID- 16911038
TI  - The evolution of development in Streptomyces analysed by genome comparisons.
AB  - There is considerable information about the genetic control of the processes by
      which mycelial Streptomyces bacteria form spore-bearing aerial hyphae. The recent
      acquisition of genome sequences for 16 species of actinobacteria, including two
      streptomycetes, makes it possible to try to reconstruct the evolution of
      Streptomyces differentiation by a comparative genomic approach, and to place the
      results in the context of current views on the evolution of bacteria. Most of the
      developmental genes evaluated are found only in actinobacteria that form
      sporulating aerial hyphae, with several being peculiar to streptomycetes. Only
      four (whiA, whiB, whiD, crgA) are generally present in nondifferentiating
      actinobacteria, and only two (whiA, whiG) are found in other bacteria, where they
      are widespread. Thus, the evolution of Streptomyces development has probably
      involved the stepwise acquisition of laterally transferred DNA, each successive
      acquisition giving rise either to regulatory changes that affect the conditions
      under which development is initiated, or to changes in cellular structure or
      morphology.

PMID- 16911039
TI  - Penicillin binding proteins: key players in bacterial cell cycle and drug
      resistance processes.
AB  - Bacterial cell division and daughter cell formation are complex mechanisms whose
      details are orchestrated by at least a dozen different proteins. Penicillin
      binding proteins (PBPs), membrane-associated macromolecules which play key roles
      in the cell wall synthesis process, have been exploited for over 70 years as the
      targets of the highly successful beta-lactam antibiotics. The increasing
      incidence of beta-lactam resistant microorganisms, coupled to progress made in
      genomics, genetics and immunofluorescence microscopy techniques, have encouraged
      the intensive study of PBPs from a variety of bacterial species. In addition, the
      recent publication of high-resolution structures of PBPs from pathogenic
      organisms have shed light on the complex intertwining of drug resistance and cell
      division processes. In this review, we discuss structural, functional and
      biological features of such enzymes which, albeit having initially been
      identified several decades ago, are now being aggressively pursued as highly
      attractive targets for the development of novel antibiotherapies.

PMID- 16911040
TI  - Central role of the respiratory syncytial virus matrix protein in infection.
AB  - Respiratory syncytial virus is the major respiratory pathogen of infants and
      children worldwide, with no effective treatment or vaccine available. Steady
      progress has been made in understanding the respiratory syncytial virus life
      cycle and the consequences of infection, but many areas of respiratory syncytial
      virus biology remain poorly understood, including the role of subcellular
      localisation of respiratory syncytial virus gene products such as the matrix
      protein in the infected host cell. The matrix protein plays a central role in
      viral assembly and, intriguingly, has been observed to traffic into and out of
      the nucleus at specific times during the respiratory syncytial virus infectious
      cycle. Further, the matrix protein has been shown to be able to inhibit
      transcription, which may be a key to respiratory syncytial virus pathogenesis.
      This review will focus on the role of the matrix protein in respiratory syncytial
      virus infection and what is known of its nucleocytoplasmic trafficking, the
      understanding of which may lead to new therapeutic approaches to combat
      respiratory syncytial virus, and/or vaccine development.

PMID- 16911041
TI  - The Desulfitobacterium genus.
AB  - Desulfitobacterium spp. are strictly anaerobic bacteria that were first isolated
      from environments contaminated by halogenated organic compounds. They are very
      versatile microorganisms that can use a wide variety of electron acceptors, such
      as nitrate, sulfite, metals, humic acids, and man-made or naturally occurring
      halogenated organic compounds. Most of the Desulfitobacterium strains can
      dehalogenate halogenated organic compounds by mechanisms of reductive
      dehalogenation, although the substrate spectrum of halogenated organic compounds
      varies substantially from one strain to another, even with strains belonging to
      the same species. A number of reductive dehalogenases and their corresponding
      gene loci have been isolated from these strains. Some of these loci are flanked
      by transposition sequences, suggesting that they can be transmitted by horizontal
      transfer via a catabolic transposon. Desulfitobacterium spp. can use H2 as
      electron donor below the threshold concentration that would allow sulfate
      reduction and methanogenesis. Furthermore, there is some evidence that syntrophic
      relationships occur between Desulfitobacterium spp. and sulfate-reducing
      bacteria, from which the Desulfitobacterium cells acquire their electrons by
      interspecies hydrogen transfer, and it is believed that this relationship also
      occurs in a methanogenic consortium. Because of their versatility,
      desulfitobacteria can be excellent candidates for the development of anaerobic
      bioremediation processes. The release of the complete genome of
      Desulfitobacterium hafniense strain Y51 and information from the partial genome
      sequence of D. hafniense strain DCB-2 will certainly help in predicting how
      desulfitobacteria interact with their environments and other microorganisms, and
      the mechanisms of actions related to reductive dehalogenation.

PMID- 16911042
TI  - How high G+C Gram-positive bacteria and in particular bifidobacteria cope with
      heat stress: protein players and regulators.
AB  - The Actinobacteridae group of bacteria includes pathogens, plant commensals,
      endosymbionts as well as inhabitants of the gastrointestinal tract. For various
      reasons, these microorganisms represent a growing area of interest with respect
      to genomics, molecular biology and genetics. This review will discuss the current
      knowledge on the molecular players that allow actinobacteria to contend with heat
      stress, with an emphasis on bifidobacteria. We describe the principal molecular
      chaperones involved in heat stress. Temporal expression of heat-shock genes based
      on functional genomics in members of the Actinobacteridae group is also
      discussed, as well as the emerging molecular mechanisms controlling the heat
      stress response.

PMID- 16911043
TI  - Human coronavirus NL63, a new respiratory virus.
AB  - From the mid-1960s onwards, it was believed that only two human coronavirus
      species infect humans: HCoV-229E and HCoV-OC43. Then, in 2003, a novel member of
      the coronavirus family was introduced into the human population: SARS-CoV,
      causing an aggressive lung disease. Fortunately, this virus was soon expelled
      from the human population, but it quickly became clear that the human coronavirus
      group contains more members then previously assumed, with HCoV-NL63 identified in
      2004. Despite its recent discovery, ample results from HCoV-NL63 research have
      been described. We present an overview of the publications on this novel
      coronavirus.

PMID- 16911044
TI  - The protein secretion systems in Listeria: inside out bacterial virulence.
AB  - Listeria monocytogenes, the etiologic agent of listeriosis, remains a serious
      public health concern with its frequent occurrence in food coupled with a high
      mortality rate. The capacity of a bacterium to secrete proteins to or beyond the
      bacterial cell surface is of crucial importance in the understanding of biofilm
      formation and bacterial pathogenesis to further develop defensive strategies.
      Recent findings in protein secretion in Listeria together with the availability
      of complete genome sequences of several pathogenic L. monocytogenes strains, as
      well as nonpathogenic Listeria innocua Clip11262, prompted us to summarize the
      listerial protein secretion systems. Protein secretion would rely essentially on
      the Sec (Secretion) pathway. The twin-arginine translocation pathway seems
      encoded in all but one sequenced Listeria. In addition, a functional flagella
      export apparatus, a fimbrilin-protein exporter, some holins and a WXG100
      secretion system are encoded in listerial genomes. This critical review brings
      new insights into the physiology and virulence of Listeria species.

PMID- 16911045
TI  - Life within a community: benefit to yeast long-term survival.
AB  - Traditionally, living organisms have often been classified into two main
      categories: unicellular and multicellular. In recent years, however, the boundary
      between these two groups has become less strict and clear than was previously
      presumed. Studies on the communities formed by unicellular microorganisms have
      revealed that various properties and processes so far mainly associated with
      metazoa are also important for the proper development, survival and behaviour of
      muticellular microbial populations. In this review, we present various examples
      of this, using a yeast colony as representative of a structured organized
      microbial community. Among other things, we will show how the differentiation of
      yeast cells within a colony can be important for the long-term survival of a
      community under conditions of nutrient shortage, how colony development and
      physiology can be influenced by the environment, and how a group of colonies can
      synchronize their developmental changes. In the last section, we introduce
      examples of molecular mechanisms that can participate in some aspects of the
      behaviour of yeast populations.

PMID- 16911046
TI  - Nurse education: time to get it right.

PMID- 16911047
TI  - The impact of role discrepancy on nurses' intention to quit their jobs.
AB  - AIMS AND OBJECTIVE: The purpose of this study was to investigate the impact of
      role discrepancy on nurses' intention to quit their jobs. BACKGROUND: Nurses
      experience role discrepancy, which refers to incompatibility between the roles
      nurses desire and expect to take, and the roles they actually engage in at work.
      However, there is a paucity of information as to how this role discrepancy
      affects nurses' intention to quit their jobs. DESIGN: A correlational design was
      used to investigate the impact of role discrepancy on nurses' intention to quit
      their jobs. METHODS: A total of 346 Australian nurses participated in this study
      by completing questionnaires. The results were analysed by t-test, polynomial
      regression and response surface analysis. RESULTS: Nurses tended to experience
      role discrepancy, in particular, in decision making with hospital policies and
      provision of patient education. The overall results show that this role
      discrepancy contributes to nurses' intention to quit their jobs. Nurses'
      intention to quit their jobs also increased when they had a low desire to engage
      in nursing roles and when they only performed a few roles. When specific
      dimensions of nursing roles were examined, a role discrepancy in the use of
      nursing skills, such as participation in decision making and providing patient
      education and emotional support, had little impact on their turnover intention.
      On the contrary, a role discrepancy in task delegation practice showed a
      significant association with nurses' intention to leave their jobs. CONCLUSIONS:
      Role discrepancy has been experienced by many nurses, and this discrepancy
      partially contributes to nurses' intention to quit their jobs. RELEVANCE TO
      CLINICAL PRACTICE: To reduce nursing turnover, it is important to create a work
      environment where nurses are inspired to engage in various nursing roles and
      their work desires are reinforced by existing work opportunities.

PMID- 16911048
TI  - Haemodynamic instability after cardiac surgery: nurses' perceptions of clinical
      decision-making.
AB  - BACKGROUND: Cardiac surgical patients are distinguished by their potential for
      instability in the early postoperative period, highly invasive haemodynamic
      monitoring technologies and unique clinical presentations as a result of
      undergoing cardiopulmonary bypass. Little is known about nurses' perceptions of
      assuming responsibility for such patients. An understanding of nurses'
      perceptions may identify areas of practice that can be improved and assist in
      determining the adequacy of current decision supports. AIM: The aim of this study
      was to describe critical care nurses' perceptions of assuming responsibility for
      the nursing management of cardiac patients in the initial two-hour postoperative
      period. DESIGN: An exploratory descriptive study based on naturalistic decision
      making. METHODS: Thirty-eight nurses were interviewed immediately following a two
      hour observation of their clinical practice. Content analysis and a systematic
      thematic analysis process called 'Framework' were used to analyse the interview
      transcripts. RESULTS: Nurses described their perceptions of managing patients in
      terms of how they felt about making decisions for complex cardiac surgical
      patients and in terms of how clinical processes unique to the admission phase
      impacted their decision-making. Nurses felt either daunted or stimulated and
      challenged when making decisions. Nurses identified handover from anaesthetists,
      settling in procedures and forms of collegial assistance as important processes
      that impacted their decision-making. CONCLUSION: Nurses' previous experiences
      with similar patients influenced how they felt about making decisions during the
      initial two-hour postoperative period, but did not alter their views about
      processes important for patient safety during this time. RELEVANCE TO CLINICAL
      PRACTICE: Feelings expressed by nurses in this study highlight the need for
      clinical supervision and appropriate allocation of resources during the immediate
      recovery period after cardiac surgery. Nurses identified ways to improve clinical
      processes that impacted their decision-making during the immediate recovery of
      cardiac surgical patients.

PMID- 16911049
TI  - Change on the horizon: issues and concerns of neophyte advanced healthcare
      practitioners.
AB  - AIMS AND OBJECTIVES: The aim was to interview new entrants to a Master's level
      programme of educational preparation for advanced healthcare practice roles. The
      objectives were to gain an understanding of their issues and concerns as they
      looked ahead to their future development and to illuminate issues concerning
      their experiences as students and as employees. BACKGROUND: As advanced practice
      roles become more widespread in the United Kingdom and abroad, nurses and other
      healthcare professionals are becoming more involved in innovation and service
      development and experiencing greater autonomy in many areas, particularly in
      regard to clinical examination and diagnosis. DESIGN: A qualitative design was
      employed to illuminate issues and concerns of new students on a Master's degree
      programme of educational preparation for advanced healthcare practitioners.
      METHODS: Two focus group interviews were conducted in 2004. Sixteen students from
      two programme cohorts participated in the two groups. FINDINGS: Two main themes
      were outlined. These were: 'opportunities for development' and 'time pressures'.
      Subcategories within these two themes are also discussed. CONCLUSIONS: Students
      undertaking Master's level preparation for advanced healthcare practitioner roles
      perceive personal and professional benefits and opportunities to develop
      innovative services to improve patient care as accruing from the programme. These
      opportunities and benefits were related to the United Kingdom national health
      policy agenda. Some role difficulties were experienced. The additional burdens
      that the programme of study provided were an issue for some, but these were
      perceived as a temporary problem, worth undergoing for the likely long-term
      benefits. RELEVANCE TO CLINICAL PRACTICE: Students undertaking educational
      preparation for advanced practice roles see themselves as innovators,
      specifically aiming to develop and improve aspects of service provision.
      Education for advanced practice roles should not be undertaken lightly, but can
      equip students with various skills, particularly regarding clinical assessment,
      and these skills should underpin practitioners' autonomy.

PMID- 16911050
TI  - Who do they think they are? Undergraduate perceptions of the definition of
      supernumerary status and how it works in practice.
AB  - AIMS AND OBJECTIVES: The aim of this study was threefold and was based on three
      research questions; how did students define supernumerary status, how was it
      implemented in practice and what effect did it have on them? BACKGROUND: Whilst
      there has been much debate about supernumerary status and its value to nursing
      practice and education there has been little work carried out from the student's
      point of view. DESIGN: The study was qualitative in nature. METHODS: Focus group
      interviews were the method of choice based on the premise that the interaction
      between students/participants would generate rich experiential data. RESULTS:
      Nine themes were generated that addressed the three questions asked. The themes
      to emerge from the category definition of supernumerary status were: not counted
      in the staff numbers and lack of student preparation. The themes to emerge from
      the category implementation of supernumerary status were: leadership style,
      experiences of mentorship, an extra pair of hands and not allowed to study. The
      themes to emerge from the category effect of supernumerary status were: their
      learning was enhanced, feelings of being used and reduction in self-confidence.
      CONCLUSIONS: There is a need to review what is meant or indeed expected from
      students who are supernumerary and increased clarity is required about what it is
      supposed to achieve. RELEVANCE TO CLINICAL PRACTICE: The status of student nurses
      in practice has a direct link to the quality of the work they produce. This has a
      domino effect that may have far reaching consequences. Making sure that they are
      clear about what is expected of them from the outset will reduce confusion and
      allow them to move forward with skills acquisition and building their experience.

PMID- 16911051
TI  - Evaluation of a nurse consultant's clinical activities and the search for patient
      outcomes in critical care.
AB  - AIMS: To describe the actual clinical activities undertaken by a critical care
      nurse consultant in an eight-bedded adult surgical high dependency unit within a
      large NHS Teaching Hospitals NHS Trust. BACKGROUND: In the United Kingdom, the
      first critical care nurse consultants were approved in 2000 following the
      Department of Health's (1999) revised career structure for nurses. Expert
      practice is a core function of the role although the nature of expert practice in
      the context of critical care is unclear. Expert practice is often deemed to be a
      feature of advanced practice and although a number of studies have investigated
      this in context of critical care, there is little insight into the nature of
      advanced practitioners' clinical practice and how it might influence patient
      outcome. DESIGN METHODS: A diary was used by a critical care nurse consultant to
      record activity during scheduled clinical sessions. Data were collected for four
      months: 39 sessions were evaluated. Qualitative data were content analysed and
      coded into categories. Clinical activities were coded, categorized and analysed
      using SPSS 11.0 for windows (SPSS Inc., Chicago, IL, USA). FINDINGS: Clinical
      activities included direct care activities, clinical leadership, education and
      training. Two main themes emerged from the qualitative data and were categorized
      as clinical reasoning and clinical instruction. Clinical activities arising from
      clinical reasoning and clinical instruction were aimed at minimizing risk and the
      provision of quality care. In doing this, one of the outcomes was the detection
      and resolution of untoward clinical occurrences. CONCLUSION: The level of
      achievement--or end point--of clinical activities was that the patient was
      established in 'a state free from risk or harm that optimises rehabilitation'. 'A
      state free from risk or harm that optimizes rehabilitation' might be one outcome
      reflecting the needs of individual critically ill patients that is sensitive to
      individual nursing contribution. RELEVANCE TO CLINICAL PRACTICE: There is
      increasing pressure on health-care professionals to identify and measure their
      individual impact on the outcome of patients. This study adds further insight
      into the complexities associated with evaluating the influence of individual
      contribution on patient outcome, especially when it is characterized by complex
      processes involving clinical judgement and decision-making.

PMID- 16911052
TI  - The lived experience of a tracheostomy tube change: a phenomenological study.
AB  - AIM: To investigate the lived experience patients have of a tracheostomy tube
      change. BACKGROUND: Few interpretive studies have looked at specific nursing
      interventions in relation to nursing practice. This study has investigated the
      lived experience of patients from an intensive care unit that have had a
      tracheostomy tube change. The tracheostomy is a significant intervention for many
      patients within critical care. METHOD: Using a phenomenological approach, guided
      by the insights of Martin Heidegger and Max van Manen, participants were
      interviewed with their responses being transcribed into a text. This text has
      been subject to hermeneutic analysis using the theories of Paul Ricoeur. This
      hermeneutic approach has required using the text (discourse) as the focus of the
      interpretation. FINDINGS: The findings of this study imply that the experience of
      a tracheostomy tube change is more complex than that of simply a physical
      sensation. There is a need for participants to prepare themselves
      psychologically, a process that requires not only the trust of nursing staff but
      also the assessment by the participant that the nursing staff member has a level
      of competence to perform the task. The need for maintaining communication and the
      ability to speak were at times more significant for participants than even the
      risk of other airway complications. RELEVANCE TO CLINICAL PRACTICE: This study
      has highlighted the potential for further interpretive studies into some of the
      more specific aspects of caring for patients that have been or are critically
      ill. The themes revealed will enable the nurse, required to change a tracheostomy
      tube, to do so with an improved level of empathy and understanding.

PMID- 16911053
TI  - The experience of fatigue for adults living with HIV.
AB  - AIMS: The aim of this study was to go beyond objective clinical assessment and
      explore the experience of fatigue and self-care strategies with adults who live
      with HIV. RATIONALE: This study responded to a perceived lack of available
      evidence to inform the practice of service providers about ways fatigue impacts
      on the lives of people with HIV. Prior understandings of fatigue are derived from
      survey or instrument-based tools or studies that do not consider the complexities
      of the personal experience that in-depth interviews can elicit. The focus remains
      generally on description, measurement or management from a biomedical
      perspective. METHODS: A qualitative study using participatory action research
      methods was conducted during 2003 with 15 adults diagnosed with HIV who perceived
      fatigue was a problem in their lives. Data were collected by individual
      interviews, researcher's notes and two participatory action research groups.
      RESULTS: Thematic analysis of data demonstrated that fatigue remains silent and
      invisible to participant's families, friends and employers. Fatigue experienced
      by people living with HIV generally also met with a lack of acknowledgement and
      understanding from health professionals. People developed self-care strategies
      over many years of trial and error. RELEVANCE TO CLINICAL PRACTICE: People living
      with a HIV seek to be acknowledged that fatigue is a legitimate concern, not only
      by health care professionals, but also people with whom they live. It is
      imperative that nurses who work with people living with HIV-related fatigue
      consider the wider social aspects of the person's life as well as physical
      symptoms. Most importantly, there then needs to be a process of engagement and
      active listening to the individual's account of their experience of fatigue.
      Advocating that fatigue is a legitimate complaint to the person living with HIV
      as well as the wider public and professional community is imperative.

PMID- 16911054
TI  - Community dwelling adults' perception of interpersonal trust vs. trust in health
      care providers.
AB  - AIMS: This study investigated community dwelling adults' definition of trust in
      health care providers vs. interpersonal trust, description of the attributes of a
      trustworthy provider, factors that influenced the development and loss of trust.
      BACKGROUND: Trust is an important part of health care relationships, however, the
      meaning of trust for patients is not well understood. Health care providers need
      to understand the meaning of trust in order to build and maintain therapeutic
      relationships with their patients. DESIGN: A descriptive qualitative research
      design was used to investigate perceptions of trust. METHODS: Semi-structured
      open-ended interviews were carried out with 32 community dwelling adults. The
      participants were recruited from church groups, senior health programs and other
      community programs. The interviews were thematically analysed for: definitions of
      interpersonal trust vs. trust in a health care provider, attributes of a
      trustworthy provider and factors that were pivotal in the development and loss of
      trust in a health care provider. RESULTS: Trust in health care providers differed
      from interpersonal trust in the role-specific attributes of the individuals.
      Trust, although influenced by having confidence in the provider's competence, was
      strongly tied to the interpersonal caring attributes of the provider. Loss of
      trust, on the other hand, was more closely allied with the issues of competency.
      CONCLUSIONS: Perceptions of trust varied greatly among this sample, reinforcing
      the significance of tailoring our approach to patients on an individual basis.
      RELEVANCE TO CLINICAL PRACTICE: Assuming that we will be trusted based on our
      role as nurses may not facilitate the development of a therapeutic relationship
      with some patients. Nurses and other health care providers need to be acutely
      aware of our patient's trust and clues of pending loss of trust because, as this
      study and other prior studies have shown, once trust in a provider is lost, it is
      nearly impossible to rebuild.

PMID- 16911055
TI  - Balancing uncertainty and acceptance: understanding Chinese women's responses to
      an abnormal cervical smear result.
AB  - AIMS AND OBJECTIVES: The aims of this study were to examine the responses of Hong
      Kong Chinese women receiving an abnormal smear result and to compare any
      differences in responses depending on the diagnosis of the abnormal smear.
      BACKGROUND: The implementation of cervical screening programmes has resulted in
      an increasing number of women receiving an abnormal smear result requiring
      cytological surveillance or referral for colposcopy. Evidence suggests that women
      frequently misunderstood such results, believing that they already have cancer.
      However, little is known about the responses of Chinese women in this situation.
      DESIGN: An exploratory qualitative study. METHODS: Face-to-face semi-structured
      tape-recorded interviews were undertaken with 66 women sampled opportunistically
      from an urban centre of a major non-governmental service provider. Amongst this
      sample, 22 women required cytological surveillance, 20 required treatment for
      vaginitis and 24 were referred for colposcopy. Thematic analysis was undertaken
      of the translated interviews within and across groups to identify categories and
      themes illustrating women's responses to an abnormal smear result. FINDINGS: An
      important difference in the comparison of the data sets was that of women's
      understanding of the cause of the abnormal result. Women with vaginitis
      understood the cause of their abnormality, whereas those in the other groups
      remained unclear about their abnormality, generating feelings of fear and
      uncertainty. Trust in practitioners influenced women's acceptance of the result.
      CONCLUSIONS: Although responses of Chinese women are similar to those in other
      population groups, with those referred for colposcopy experiencing greater
      anxiety than those undergoing cytological surveillance, balancing feelings of
      uncertainty and acceptance influenced Chinese women's responses to their abnormal
      results and allowed them to make sense of their result in their everyday life.
      Trust in the practitioner was essential to the acceptance of their result.
      RELEVANCE TO CLINICAL PRACTICE: Such findings highlight implications for nursing
      practice, in particular developing information-giving strategies and targeted
      information to help women manage feelings of uncertainty. The importance of
      trusting professional relationships in determining women's acceptance of an
      abnormal result is also highlighted. The findings suggest nurses working with
      Chinese women should consider the underlying influence of culture on women's
      beliefs and actions.

PMID- 16911056
TI  - Being asked not to tell: nurses' experiences of caring for cancer patients not
      told their diagnosis.
AB  - AIMS AND OBJECTIVES: The aim of the primary research was to investigate the
      impact of the nurse-patient relationship on clinical learning and subsequently
      clinical practice. Coincidently, 32 participants, all Registered Nurses in Hong
      Kong, provided details of nurse-patient encounters involving withholding of a
      cancer diagnosis. BACKGROUND: The changing face of clinical practice and cancer
      care has fuelled discussion and debate around disclosure or non-disclosure of the
      diagnosis of cancer, global consensus on this issue still does not exist. In
      different countries there is marked variation in how and what a patient may be
      told about their diagnosis and prognosis. There is considerable variability in
      the reported rate of cancer diagnosis disclosure across studies and countries.
      Being asked not to tell a patient their diagnosis of cancer presents many
      problems for nurses caring for those patients. The issue of non-disclosure
      directly affects nurses and their clinical practice. METHODS: This paper reports
      one of the findings of a large international qualitative study informed by
      phenomenology into the perceptions of nurses about caring for a patient with a
      diagnosis of cancer. RESULTS: Responses from participants revealed considerable
      difficulties for nurses when caring for patients who were not informed of their
      diagnosis. They recounted having learned from the encounters but remarked on the
      negativity of the experience. They discussed their inability to act decisively in
      the past situations but expressed hope that they had found a resolve to act in
      future. RELEVANCE TO CLINICAL PRACTICE: Although, overwhelmingly, participants
      doubted they would actually be able to change the reality of practice. The
      identified care episode and the nurse-patient relationship, according to
      participants, did change their clinical practice but often not for the better.

PMID- 16911057
TI  - Relatives in end-of-life care--part 1: a systematic review of the literature the
      five last years, January 1999-February 2004.
AB  - AIM: To review systematically research conducted during the past five years
      focusing on the relatives' situation and needs in end-of-life care. BACKGROUND
      AND AIM: That relatives make a large contribution in the care of the dying is
      well-known. In this situation, relatives often have to solve many new practical
      problems in the care as well as dealing with the sorrow of both themselves and
      the dying person. In recent years, palliative care has been developed in many
      countries and many new studies have been carried out. METHODS: A systematic
      search of the literature was performed in the CINAHL and Medline databases. Of
      the 94 papers analysed, there were 59 qualitative and 35 quantitative studies
      with differing designs. The studies were carried out in 11 countries and were
      published in 34 different journals. RESULTS: The results were categorized in two
      main themes with several subthemes: (1) being a close relative--the situation:
      (i) exposed position--new responsibility, (ii) balance between burden and
      capacity and (iii) positive values; (2) being a close relative--needs: (i) good
      patient care, (ii) being present, (iii) knowing and communicating and (iv)
      support from and trusting relationship with the professional. The relative's
      feelings of security and trust in the professional were found to be of great
      importance. CONCLUSION: More than twice as many studies had a
      descriptive/explorative design, which is of importance in the assessment of
      evidence. However, different studies complement one another and in summary, it
      can be said that analytic evidence is unequivocal: good patient care,
      communication, information and the attitude of the professional are of decisive
      importance regarding relatives' situation. These results are also in accord with
      earlier review studies. RELEVANCE TO CLINICAL PRACTICE: Staff members have a
      great deal of responsibility for assuring that the patient feels as good as
      possible, facilitating relatives' involvement based on the family's wishes and
      limiting the stress and difficulties experienced by the family. The results
      showed that the relative's satisfaction could depend on the attitude of the
      professional as well as on good communication, good listening and good
      information. This can also be viewed as a prerequisite for the professional to
      get to know the family and to provide 'care in the light'.

PMID- 16911058
TI  - Nursing the clinic vs. nursing the patient: nurses' experience of a day hospital
      chemotherapy service.
AB  - AIMS AND OBJECTIVES: This study sought to explore the nurses' experience of a day
      hospital chemotherapy service in an acute general hospital in Northern Ireland
      and how this compared with their experience of working in an inpatient setting.
      BACKGROUND: Despite the many changes taking place in cancer care delivery, little
      research has been conducted on nurses' experience of working in more acute cancer
      treatment settings. Research conducted to date has tended to focus on the role of
      nurses in wards, hospices and palliative care settings. DESIGN: This Heideggerian
      hermeneutic phenomenological study explored nurses' lived experience of day
      hospital chemotherapy service. METHOD: Face-to-face focused in-depth interviews
      were conducted with the total population of nurses who worked in the day hospital
      at the time of data collection (n = 10). Data analysis involved a two-staged
      approach, the analysis of narratives and narrative analysis, based on the work of
      Polkinghorne (1995). CONCLUSIONS: The nurses' viewed their experience of the
      chemotherapy day hospital as having both positive and negative dimensions. The
      positive dimensions included an increased sense of autonomy and the challenge of
      developing new skills, while the negative dimension included a perceived decrease
      in their caring role: (i) The individual characteristics of the nurse were seen
      to have a key influence on caring experience; (ii) Role changes led to a
      perceived dichotomy between their actual and aspired role and their caring and
      clinical role. RELEVANCE TO CLINICAL PRACTICE: There is a need to achieve a
      balance between delivering a clinical role (administering chemotherapy) while
      maintaining the centrality of the nurse-patient relationship. This can be likened
      to achieving a balance between 'nursing the clinic' alongside 'nursing the
      patient'. These findings have implications for the discourse on caring within
      other outpatient type clinics and discourse on cancer nursing as therapy and the
      culture of the cancer clinic.

PMID- 16911059
TI  - Turkish nurses' information about, and administration of, chemotherapeutic drugs.
AB  - AIM: The aim of this study was to determine both the level of information that
      nurses possessed and the method of administration nurses used during
      chemotherapeutic drug preparation and administration. BACKGROUND: While
      compliance with the regulations related to chemotherapeutic drug preparation and
      administration seems to be very difficult, it is at the same time vital. METHODS:
      This descriptive study was conducted between 1 May 2002 and 1 May 2003 in the
      chemotherapy administration units of all hospitals in Eskisehir, west Turkey. The
      sample consisted of 121 nurses. Data were obtained first via questionnaire forms
      developed by the researchers to learn the level of awareness concerning exposure
      to chemotherapy. This was then followed up by the completion of observation forms
      during drug administrations. RESULTS: The average score for information levels
      pertaining to nurses' protection of the environment was 7.82 +/- 0.38 of a total
      of 14 points, and that of self-protection was 7.94 +/- 0.24 of a total of 11
      points. Nurses showed that their actual administration method was insufficient
      according to their level of information, with average administration evaluations
      of 5.46 for protection of the environment and 6.59 for self-protection. The ratio
      for nurses' usage of the safety cabinet during the preparation of
      chemotherapeutic drugs was very low at 14.2%. Only 7.4% of nurses had received in
      service education about chemotherapeutics. CONCLUSION: In order to ensure the
      taking of sufficient preventive precautions during the preparation and
      administration of chemotherapeutic agents, hospitals should be required to
      provide sufficient equipment and to give this precedence in hospital politics.
      RELEVANCE TO CLINICAL PRACTICE: Healthcare workers who prepare and administer
      chemotherapeutic drugs may experience the cytotoxic effects of the drugs through
      direct skin contact, respiratory and digestive system exposure, and these effects
      are vital to human life. Thus, it has been recognized that nurses' information
      and administrations during preparation and administration of chemotherapeutic
      drugs are of utmost vital importance in removing the harmful effects of
      chemotherapeutic agents.

PMID- 16911060
TI  - Quality of life in palliative care cancer patients: a literature review.
AB  - AIMS AND OBJECTIVES: [corrected] This review of the literature intended to get
      insight into the international standards of quality of life assessment in
      palliative care, the conceptual and research literature addressing illness
      related quality of life and an examination of how nurse researchers define and
      assess this concept in the context of terminally ill cancer patients. Clearly
      stated goals for measuring quality of life as well as an understanding of the
      pragmatic and theoretical explanations for current trends in quality of life
      measurement are fundamental to this focus. BACKGROUND: Most clinicians and
      researchers agree that the primary goal of palliative care is to optimize the
      quality of life of patients with advanced incurable diseases through control of
      physical symptoms and attention to the patient's psychological, social and
      spiritual needs. Palliative care therefore is the achievement of the best quality
      of life for patients and their families. Consequently, the outcomes of care
      should be measured in terms of the extent to which this goal is achieved. Quality
      of life is difficult to define and measure; it is a multidimensional, dynamic and
      subjective concept. During the past decade, multidisciplinary research measuring
      the impact of cancer and its treatment on the quality of people's lives escalated
      rapidly in international literature but not in the German speaking European
      countries. This international escalation was accompanied by a proliferation of
      measurement strategies and tools. Nursing shared this interest and began to
      generate substantive research of the phenomenon. In the oncology and palliative
      care nursing societies quality of life and numerous closely related areas of
      symptom management rank among the highest research priorities. METHOD: This paper
      examines nursing literature published between 1990 and 2004, retrieved through a
      computer review of MEDLINE and Cumulative Index of Nursing and Allied Health
      Literature. The review includes reports that systematically describe or measure
      the quality of life of people with a terminal cancer in palliative care as a
      variable of interest. This article also describes conceptual and operational
      definitions of quality of life and explores the implicit and explicit goals of
      research. RESULTS: Quality of life is a concept relevant to the discipline of
      nursing. Nurses, especially oncology and palliative care nurses, actively
      contributed to the development of the quality of life concept through instrument
      development and population description. CONCLUSION: Nurses working in German
      palliative care settings do change the quality of life of patients they care for,
      but there are no systematic standards of assessing these outcomes. RELEVANCE TO
      CLINICAL PRACTICE: There are challenges related to measuring quality of life in
      patient-focused palliative care and research. Systematic quality of life
      assessment in all palliative care settings will establish quality assurance and
      the further development of this very young discipline in Germany.

PMID- 16911061
TI  - Psychological approaches for the nursing management of chronic pain: part 2.
AB  - AIMS AND OBJECTIVES: The aim of this article was to present the ways that nurses
      can integrate psychological approaches into their management of chronic pain
      conditions using a biopsychosocial framework. Communication, the importance of
      the patient-practitioner interaction, the role of education and provision of
      information, reassurance and reduction of anxiety and the use of coping
      strategies training in the management of chronic pain are reviewed alongside the
      key skills of nursing. BACKGROUND: This is the second part of a two-part article.
      Part 1 was a discussion of psychosocial factors associated with chronic pain
      conditions and the psychological approaches used in the management of these
      conditions. CONCLUSIONS: It is identified that key nursing skills often equate to
      the requirements of the psychological approaches, therefore specific techniques
      from a cognitive-behavioural framework can be readily applied, integrated and
      used by nurses in the management of chronic pain conditions. RELEVANCE TO
      CLINICAL PRACTICE: Commonly utilized nursing skills are similar to those required
      for cognitive-behavioural therapy. It is reasonable to assume therefore that
      nurses can and should be involved in effectively managing the psychological
      aspects associated with chronic pain conditions.

PMID- 16911062
TI  - Reporting of painful conditions in nursing homes.

PMID- 16911063
TI  - Commentary on Nystedt A, Hogberg U & Lundman B (2005) The negative birth
      experience of prolonged labour: a case-referent study. Journal of Clinical
      Nursing 14, 579-586.

PMID- 16911065
TI  - Commentary on Armitage G (2005) Drug errors, qualitative research and some
      reflections on ethics. Journal of Clinical Nursing 14, 869-875.

PMID- 16911068
TI  - Wavelength division scanning for two-photon excitation fluorescence imaging.
AB  - We investigate wavelength division scanning for two-photon excitation
      fluorescence imaging. Two-photon imaging using lateral wavelength division
      scanning is demonstrated. In addition, we theoretically analyse the spatial and
      temporal properties of a femtosecond laser beam focused by a Fresnel lens and
      investigate the feasibility of axial scanning using wavelength division.

PMID- 16911069
TI  - Electron microscopy and diffraction of radiation-sensitive nanostructured
      materials.
AB  - Soft matter research of natural organic and synthetic nanomaterials is an area in
      nanoscience and technology that has been growing particularly quickly in recent
      years. The materials under investigation are sensitive to high-energy electrons.
      Any structure characterization using electron microscopy thus requires special
      care. First, we illustrated this on naturally grown nanotubes observed by normal
      and cryogenic scanning electron microscopy. Second, we studied the ordering and
      orientation of the mesophase in template-grown nanotubes and nanorods containing
      discotic liquid crystals without and with doping, as desired. For these studies,
      we mainly used transmission electron diffraction and microscopy at low-dose
      conditions, high-efficiency image acquisition, and cryoprotection of the
      structures at liquid helium temperature. Additional analytical information was
      obtained by electron energy filtering observations.

PMID- 16911070
TI  - A novel real-time confocal imaging technique for examining host-implant
      interfacial shear failure patterns.
AB  - In clinical practice, implant failure usually occurs at the biomaterial-host
      tissue interface, typically involving both biomechanical and biochemical
      mechanisms. By definition, any new 'bioactive' material will bond to living bone
      but, prior to clinical use, interface formation, performance, longevity and
      failure pattern characterizations are necessary. The common missing link in many
      biomaterial interface investigations is imaging at the point of presumed loaded
      failure. The novel real-time confocal technique described here allows bond
      strength, formation rate, longevity and bone-material interface failure pattern
      characterization for a wide range of biomaterials capable of forming tissue
      interfaces, in one real-time imaged microshear stress process, conducted using
      imaging frame matched load/displacement data acquisition under relatively normal
      near in vivo environmental conditions. The technique, validated by post-failure
      scanning electron microscopy imaging, revealed that more slowly reacting melt
      derived 45S5 glass materials produced stronger and more stable long-term
      interfaces than faster reacting microporous bioactive sol-gel glasses.

PMID- 16911071
TI  - Statistical analysis of reduced pair correlation functions of capillaries in the
      prostate gland.
AB  - Blood capillaries are thread-like structures that may be considered as an example
      of a spatial fibre process in three dimensions. At light microscopy, the
      capillary profiles appear as a planar point process on sections. It has recently
      been shown that the observed pair correlation function g(r) of the centres of the
      fibre profiles on two-dimensional sections may be used to estimate the reduced
      pair correlation function of stationary and isotropic fibre processes in three
      dimensions. In the present study, we explored how this approach may be extended
      to statistical analysis of reduced g-functions of capillaries from multiple
      specimens of different groups and with replicated observations. The methods were
      applied to normal prostatic tissue compared with prostate cancer. Confidence
      intervals for the mean reduced g-functions of groups were estimated for fixed r
      values parametrically using the t-distribution, and by bootstrap methods. Each
      estimated reduced g-function was furthermore characterized in terms of its first
      maximum and minimum. The mean length of capillaries per unit tissue volume was
      significantly higher in prostate cancer tissue than in normal prostate tissue.
      Significant differences between the mean reduced g-functions of malignant and
      benign lesions could be demonstrated for two domains of r-values. In general,
      bootstrap-based confidence intervals were slightly wider than parametrically
      estimated confidence intervals. Falsely negative lower bounds of the intervals,
      which sometimes arose using the parametric approach, could be avoided by the
      bootstrap method. Testing of group mean values for significant differences by the
      bootstrap method yielded more conservative results than multiple t-tests. The
      functional value of the first maximum of the reduced g-function and a global
      statistical parameter of short-range ordering was significantly reduced in the
      carcinoma group. Prostate cancer tissue is more densely supplied with capillaries
      than normal prostate tissue and the three-dimensional arrangement of the vessels
      differs with respect to interaction at various distance ranges. In the local
      approach used here, bootstrap methods can be used as a robust statistical tool
      for the computation of confidence intervals and group comparisons of mean reduced
      g-functions at specific ranges of interaction.

PMID- 16911072
TI  - Automatic identification of Mycobacterium tuberculosis by Gaussian mixture
      models.
AB  - Tuberculosis and other kinds of mycobacteriosis are serious illnesses for which
      early diagnosis is critical for disease control. Sputum sample analysis is a
      common manual technique employed for bacillus detection but current sample
      analysis techniques are time-consuming, very tedious, subject to poor specificity
      and require highly trained personnel. Image-processing and pattern-recognition
      techniques are appropriate tools for improving the manual screening of samples.
      Here we present a new technique for sputum image analysis that combines invariant
      shape features and chromatic channel thresholding. Some feature descriptors were
      extracted from an edited bacillus data set to characterize their shape. They were
      statistically represented by using a Gaussian mixture model representation and a
      minimal error Bayesian classification procedure was employed for the last
      identification stage. This technique constitutes a step towards automating the
      process and providing a high specificity.

PMID- 16911073
TI  - Demonstration of lanthanum in liver cells by energy-dispersive X-ray
      spectroscopy, electron energy loss spectroscopy and high-resolution transmission
      electron microscopy.
AB  - The appearance of lanthanum in liver cells as a result of the injection of
      lanthanum chloride into rats is investigated by advanced transmission electron
      microscopy techniques, including electron energy loss spectroscopy and high
      resolution transmission electron microscopy. It is demonstrated that the
      lysosomes contain large amounts of lanthanum appearing in a granular form with
      particle dimensions between 5 and 25 nm, whereas no lanthanum could be detected
      in other surrounding cellular components.

PMID- 16911074
TI  - A flexible instrument control and image acquisition system for a scanning
      electron microscope.
AB  - We have developed an instrument control and image acquisition system for use with
      scanning electron microscopes. By making the system flexible over a wide range of
      operating voltages, scan generation and image acquisition modes can be easily
      accommodated to a wide range of instruments. We show the implementation of this
      system for use with a custom-built low-voltage scanning electron microscope. We
      then explore the simple modifications that are required for control of two
      instruments intended for use as free electron lasers.

PMID- 16911075
TI  - Characterization of the three-dimensional structure of a metallic foam during
      compressive deformation.
AB  - X-ray microtomography has been employed to collect three-dimensional images of
      aluminium closed-cell foam, enabling the internal structure to be characterized
      in three dimensions. An experimental technique and image analysis approach has
      been developed, and is described, in terms of the labelling of cells and the
      extraction of quantitative data such as the cell volume and cell compression. An
      in situ compressive deformation experiment has been performed on a single sample
      in order to illustrate the approach. The effect of the three-dimensional cellular
      structure on the mechanisms of deformation suggests not only the position of
      large cell volumes to be very important in the local concentration of stress, but
      also the distribution of cell volumes of immediate neighbours.

PMID- 16911076
TI  - Use of confocal linescan to document ciliary beat frequency.
AB  - We present a method to document ciliary beat frequency with the linescan function
      of a scanning confocal microscope, using ciliated tracheal cells and free
      swimming rotifers as examples. Depending on the clarity of the original data, the
      ciliary beat frequency can be determined from the confocal linescan directly or
      from an intensity linescan analysis of the original data. Fast Fourier transform
      treatment of the data can be used to verify the derived ciliary beat frequency.
      The linescan approach allows analysis of simple ciliary movements displayed by
      the ciliated tracheal cells, as well as complex movements performed by free
      swimming rotifers while feeding.

PMID- 16911077
TI  - Linear least-squares fit evaluation of series of analytical spectra from planar
      defects: extension and possible implementations in scanning transmission electron
      microscopy.
AB  - In a previous paper, a new technique was introduced to determine the chemistry of
      crystallographically well-defined planar defects (such as straight interfaces,
      grain boundaries, twins, inversion or antiphase domain boundaries) in the
      presence of homogeneous solute segregation or selective doping. The technique is
      based on a linear least-squares fit using series of analytical (electron energy
      loss or energy-dispersive X-ray) spectra acquired in a transmission electron
      microscope that is operated in nano-probe mode with the planar defect centred
      edge-on. First, additional notes on the use of proper k-factors and determination
      of Gibbsian excess segregation are given in this note. Using simulated data sets,
      it is shown that the linear least-squares fit improves both the accuracy and the
      robustness to noise beyond that obtainable by independently repeated
      measurements. It is then shown how the method originally developed for a
      stationary nano-probe mode in transmission electron microscopy can be extended to
      a focused electron beam that scans a square region in scanning transmission
      electron microscopy. The necessary modifications to scan geometry and
      corresponding numerical evaluation are described, and three different practical
      implementations are proposed.

PMID- 16911079
TI  - Incidence of Kawasaki disease in Japan: the nationwide surveys of 1999-2002.
AB  - BACKGROUND: The purpose of the present study was to describe the results of
      nationwide epidemiologic surveys of Kawasaki disease for the 4 year period 1999
      2002. METHODS: The design is a retrospective incidence survey. The patients
      reported in these two surveys are all new patients who were reported during the
      two study periods (1999-2000 and 2001-2002), although the data were collected
      retrospectively. A questionnaire was sent to all pediatric departments of
      hospitals with 100 beds or more throughout Japan, requesting data on patients
      with Kawasaki disease, such as sex, age, date of first hospital visit,
      recurrence, and cardiac lesions. RESULTS: The total number of patients reported
      in the 4 year period 1999-2002 was 32 266 (18 604 male, 13 662 female), with an
      average annual incidence of 137.7 per 100 000 children younger than 5 years old.
      The male/female ratio was 1.30. The incidence peaked at 9-11 months of age, and
      the proportion of patients under 1 year of age was 26%. The monthly distribution
      had a high peak in January and a gradual increase in summer. Geographically, the
      high-incidence areas were limited to certain prefectures and moved from year to
      year. The cardiac lesions at acute stage and cardiac sequelae occurred more in
      children under 1 year and older than 4 years. Among the principal symptoms, fever
      persisting >or=5 days occurred most commonly, followed by conjunctival
      congestion, changes in lips and oral cavity, polymorphous exanthema, and changes
      of extremities. Cervical lymphadenopathy occurred less. CONCLUSION: More than 32
      000 patients with Kawasaki disease during the 4 year period 1999-2002 were
      reported to the nationwide incidence surveys. The number of patients is steadily
      increasing despite the decrease of children. The seasonal variation, geographical
      distribution, and age-specific distribution support the infection theory for the
      etiology of Kawasaki disease.

PMID- 16911080
TI  - Results of clinical surveillance during the Japanese first palivizumab season in
      2002-2003.
AB  - BACKGROUND: In Japan, palivizumab was approved in 2002 for prophylaxis of severe
      respiratory syncytial virus disease in high-risk infants. In order to evaluate
      the efficacy and safety of this drug, a questionnaire survey was conducted.
      METHODS: A questionnaire was sent to member institutions of the Japan
      Neonatologist Association. The subjects were premature infants who were
      considered possible candidates for treatment with palivizumab. RESULTS: A total
      of 6302 case reports, including those of 2806 infants receiving palivizumab
      (group P) and 3496 infants not receiving palivizumab (group NP), respectively,
      were retrieved. Background characteristics revealed significant lower gestational
      age (GA) and birthweight for group P (P < 0.0001). Sex ratio did not differ
      significantly, while use of oxygen and mechanical ventilation in the neonatal
      intensive care unit, and presence of chronic lung disease were significantly
      higher for infants in group P (P < 0.0001). When comparison of hospitalization
      rate for respiratory symptoms was performed with stratification by eligibility
      criteria, in the group of infants born at 29-35 weeks GA the hospitalization rate
      was 4.0% and 5.7% in groups P and NP, respectively (P < 0.05). Multivariate
      analysis also showed that prophylaxis with palivizumab was the only variable that
      significantly decreased rate of hospitalization (odds ratio 0.630, P= 0.0053).
      The incidence of adverse events associated with the administration of palivizumab
      was low. CONCLUSION: In this non-randomized questionnaire survey, multivariate
      analysis showed that palivizumab significantly decreased the rate of
      hospitalization due to respiratory symptoms for infants born prematurely at 29-35
      weeks GA. These data confirmed the efficacy and safety of palivizumab.

PMID- 16911081
TI  - Retinoblastoma in Turkey: survival and clinical characteristics 1981-2004.
AB  - BACKGROUND: In this study, the authors aim to describe the survival and clinical
      characteristics of 141 retinoblastoma cases treated at Cerrahpasa Medical
      Faculty, University of Istanbul, Istanbul, Turkey, between 1981 and 2004. METHOD:
      The authors retrospectively analyzed the clinical records of 141 children (177
      eyes) diagnosed with retinoblastoma and treated between 1981 and 2004.
      Information on gender, laterality, age at diagnosis, presenting signs, spread of
      tumor, treatment modality, survival rate, and family history were collected.
      RESULTS: A total of 105 cases (74.5%) were unilateral and 36 cases (25.5%) were
      bilateral. The mean age overall at the time of diagnosis was 25 months; in
      unilateral cases, 29 months; and in bilateral cases, 16 months. The most common
      presenting signs were leukocoria (116 cases, 82%), strabismus (14 cases, 10%) and
      proptosis (11 cases, 8%). A total of 28 cases had orbital extension, nine
      patients had central nervous system invasion, and five cases exhibited bone
      marrow involvement. In total, 16 patients (11%) had a family history of
      retinoblastoma. One case developed a secondary neoplasm. The 3 year cumulative
      survival rate of 141 patients was 89.69% (unilateral, 90.74%; bilateral 87.35% P
      = 0.9371, P > 0.05, log rank test). CONCLUSION: The study's survival rate was
      similar to developed countries. The success in higher survival rates is based on
      the authors multidisciplinary team approach done by the same group and the
      support of the authors' clinic and government in sponsoring the medical insurance
      of all patients.

PMID- 16911082
TI  - Suicide attempts versus suicidal ideation in bulimic female adolescents.
AB  - BACKGROUND: Suicide attempts by adolescents continue to be a major public health
      problem. The purpose of this study was to examine the difference in the family
      functioning and sociopsychopathological risk factor relationship between female
      bulimic adolescents with suicidal ideation only, and those who attempted suicide.
      METHODS: A group of 211 patients were observed for 12 months. Data from 63
      subjects (SUG [suicide group], age 17.2 +/- 1.3 years) who had attempted suicide
      were then compared with 148 (control group, age 18.1 +/- 1.5 years) who had
      expressed suicidal ideation but did not follow through. RESULTS: Those in the
      suicide attempt group had been exposed more frequently to physical/sexual
      violence in childhood. As adults they either lived alone or were dissatisfied
      with their partnership. The frequency of borderline personality disorders and
      depressive disorders in this group was significant. Psychosomatic symptoms,
      disturbed coenesthesia, substance abuse, social impairment and interference with
      their perception of their own life circumstances, as well as their job
      performance, often preceded the suicide attempt. Nine genuine risk factors that
      occurred significantly more often in the SUG were calculated out of all the
      stress factors using stepwise logistic regression: 'as a child I was even hit
      with a stick or whip', 'I had no set orientation in life', 'I had a feeling of
      loneliness despite family and friends', 'I could not relax', 'incapable of
      dealing with the public', 'I do not like to be touched', 'parents have
      psychiatric disorders', 'misuse of stimulants', and 'as a child I felt lonely'
      (odds ratio, 10.56-1.90). CONCLUSION: Adverse family experiences and multiple
      sociopsychopathological factors may increase the risk of suicide in female
      bulimic adolescents.

PMID- 16911083
TI  - Environmental tobacco smoke exposure in school children: parent report and urine
      cotinine measures.
AB  - BACKGROUND: Environmental tobacco smoke (ETS) in the home continues to be a major
      health risk for children around the world. Measuring ETS is a central feature of
      clinical and epidemiological studies, with children's exposure often assessed
      through parental estimates. The authors examined the relationship between parent
      reported estimates of children's exposure to ETS and children's urinary cotinine
      levels and evaluated the ETS exposure and its effect on respiratory health in
      children. METHODS: A total of 188 school children were included in the study.
      Parents were asked to complete a questionnaire about their smoking habits, their
      children's respiratory morbidity status and housing conditions. Urinary cotinine
      levels were measured in children. RESULTS: According to the responses, 72.3% of
      the children came from households with smokers, and 34.6% had daily exposure to
      ETS. When urine cotinine levels of >10 ng/mL were used as the yardstick of
      exposure, 76% of the children were identified as ETS exposed. No relation was
      detected between the symptoms of respiratory tract diseases and ETS exposure. To
      determine the amount of ETS exposure, the contribution of parental reports was
      low. CONCLUSION: To evaluate the level of ETS exposure of children, the parents'
      reports were not reliable. The addition of a biological measure results in a more
      informative estimate of ETS exposure in children.

PMID- 16911084
TI  - Transient hyperphosphatasemia after pediatric liver transplantation.
AB  - BACKGROUND: Transient hyperphosphatasemia of infancy and early childhood is
      characterized by transiently increased serum activity of alkaline phosphatase
      (ALP), predominantly its bone or liver isoform, in children under 5 years of age.
      There is little information on the rate of transient hyperphosphatasemia in
      pediatric liver transplant recipients. METHODS: Patients who underwent liver
      transplantation at Ege University Organ Transplantation and Research Center,
      Izmir, Tureky, between January 1998 and January 2005, were included in the study.
      A total of 70 paediatric liver recipients' medical records were analyzed
      retrospectively. RESULTS: Transient isolated hyperphosphatasemia was observed in
      two of 70 patients and the rate of transient hyperphosphatasemia was estimated to
      be 2.8% in pediatric liver transplant recipient. Diarrheal episode was noted
      prior to the peak ALP activity in both cases. In one case the causative agent was
      not found, whereas in the other case Rotavirus was detected in a stool specimen.
      ALP activity normalized at 4 months and 18 days in the first and second cases,
      respectively. They continue follow up at the outpatient clinics with stable graft
      function. CONCLUSION: It is important to know that very high ALP levels can be
      seen without underlying significant pathology and the benign nature of the
      condition to avoid unnecessary investigations.

PMID- 16911085
TI  - Possible effect of leptin on renal magnesium excretion in adolescent patients
      with type 1 diabetes.
AB  - BACKGROUND: Hypomagnesaemia and hyperleptinemia are common in patients with
      diabetes. Moreover, it has been demonstrated that leptin stimulates diuresis and
      natriuresis. The aim of this study was to evaluate the relationship between serum
      leptin, serum magnesium (Mg) and urinary Mg/urinary creatinine levels in patients
      with type 1 diabetes. METHODS: Serum leptin and Mg and urinary Mg/urinary
      creatinine levels were measured in 67 patients with diabetes (33 girls and 34
      boys). The age, diabetes duration, anthropometric and metabolic parameters of the
      subjects were matched between girls and boys. The relation of serum leptin levels
      to serum and urinary Mg/urinary creatinine levels was assessed. RESULTS: Serum
      leptin levels of girls with diabetes were higher than those of the boys (14 +/-
      5.3 microg/L vs 5.8 +/- 1.5 microg/L, P < 0.001, respectively). The differences
      for serum Mg and for urinary Mg/urinary creatinine levels were not significant
      between girls and boys with diabetes. Leptin levels were correlated with urinary
      Mg/urinary creatinine levels in both girls and boys (r = 0.39, P = 0.02 and r =
      0.37, P = 0.03, respectively). In a multivariate regression model, leptin emerged
      as independent correlates for mean urinary Mg/urinary creatinine in both girls
      and boys with the total variance explained being 14%, and 15%, respectively.
      CONCLUSION: The data suggest that serum leptin might be related to increased
      urinary Mg loss in patients with type I diabetes.

PMID- 16911086
TI  - Urease activity does not reflect the degree of colonization by Helicobacter
      pylori in children.
AB  - BACKGROUND: Urea breath test is an accurate method for the diagnosis of
      Helicobacter pylori infection in children. This test could estimate the bacterial
      load by measuring the urease activity in gastric mucosa. The aim of the study was
      to correlate the result of 13C-urea breath test (13C-UBT) and histological
      estimative for bacterial colonization and severity of inflammatory infiltrate.
      METHODS: Forty-four patients (mean age 8.54 +/- 3.9 years) with dyspeptic
      symptoms were evaluated. Patients were evaluated through endoscopy and 13C-UBT.
      Helicobacter pylori infection was defined by histology, rapid urease test and 13C
      UBT. Breath test results were expressed by delta over baseline (DOB) and urea
      hydrolysis rate (UHR). Test results were treated logarithmically for statistical
      analysis. RESULTS: There was a significant inverse correlation between age and
      Log DOB (-0.501, P= 0.0005), but there was no relationship between Log UHR and
      age (-0.148, P= 0.336). The study did not find correlation between the breath
      test result and histological grades for mononuclear infiltrate, neutrophilic
      infiltrate and bacterial density. CONCLUSION: The 13C-UBT does not estimate the
      severity of histological findings in children with Helicobacter pylori infection.
      The results of the breath test should be interpreted in a qualitative way.

PMID- 16911087
TI  - Topical treatment of molluscum contagiosum with imiquimod 5% cream in Turkish
      children.
AB  - BACKGROUND: Molluscum contagiosum (MC) is caused by a poxvirus which produces
      cutaneous lesions appearing as small, firm, umbilicated papules. Lesions of MC
      are most commonly seen in young children. Transmission is through viral
      particles, which remain on surfaces, autoinoculation, or from contact with open
      lesions. There are many options for treatment of MC and these may be broadly
      subdivided into destructive, immunological and antiviral therapies. An
      alternative treatment would be desirable in pediatric patients. Imiquimod (IQ) is
      a member of immune response modifiers. METHODS: Here, the results of 12 Turkish
      pediatric patients with MC who used IQ 5% cream (aged between 3-13 years; six
      boys, six girls) are given. The cream was applied by the mothers in the evening,
      three times per week every other day up to 16 weeks. RESULTS: One of the patients
      gave up the treatment because of Influenza-like symptoms, and two of them because
      of the progress in the lesions continued. In seven of the remaining nine
      patients, total recovery was achieved. Local side-effects in patients were well
      tolerated. CONCLUSION: When all the patients affected with MC who exclusively
      used IQ 5% cream as mentioned in the literature were studied, 35 of 83 patients
      (42.2%) had complete clearance. These have differences in the form and duration
      of application. IQ 5% cream can be preferred in the treatment of children with MC
      because of its applicability at home, easy application and good tolerability.
      However, different application methods and suitable treatment methods should be
      determined.

PMID- 16911088
TI  - Vater's papillary stenosis in a child with abdominal pain.

PMID- 16911089
TI  - Creatine monohydrate therapy in a Leigh syndrome patient with A8344G mutation.

PMID- 16911090
TI  - Factor XIII in Henoch-Schonlein purpura with isolated gastrointestinal symptoms.

PMID- 16911091
TI  - Two patients with arthrogryposis-renal tubular dysfunction-cholestasis syndrome
      in a Japanese family.

PMID- 16911092
TI  - Unilateral renal agenesis presenting with acute obstructive postrenal failure
      following administration of hydration fluid.

PMID- 16911093
TI  - Juxtapapillary hemangioblastoma as a manifestation of von Hippel-Lindau disease.

PMID- 16911094
TI  - 1H-magnetic resonance spectroscopy in a case of Moyamoya disease with
      revascularization surgery.

PMID- 16911095
TI  - Percutaneous removal of a peripherally inserted central catheter remnant using
      cardiac catheterization.

PMID- 16911096
TI  - Type I diabetes mellitus, Hashimoto's thyroiditis and celiac disease in an
      adolescent with Down syndrome.

PMID- 16911097
TI  - Dental caries paradigms in diagnosis and diagnostic research.
AB  - In this article, the fundamentals of caries diagnosis are reviewed from the three
      component perspectives, namely the strategy, the logics, and the tactics.
      Strategy concerns the objectives of the diagnostic process (i.e. why we diagnose
      caries). The logics describe how we assemble and evaluate the information
      collected and how this leads to an assessment of diagnostic value. Finally,
      tactics are about how we collect the information necessary to arrive at a correct
      diagnosis. We argue that the hitherto-dominant essentialistic caries paradigm
      should be replaced by a nominalistic caries concept. This allows us to circumvent
      the problem of a lack of a caries gold standard and to proceed in caries
      diagnostic research to find the diagnostic methods that result in the best health
      outcomes for our patients. We also demonstrate the limitations of the medical
      model when attempting to understand caries diagnosis, and adhere to the Bader &
      Shugars caries script model. It is concluded that the current caries profile,
      characterized by lower prevalence and extent, and slower progression, has
      increased the need for an academic strengthening of the dental curriculum with
      respect to diagnostic reasoning and clinical decision-making processes.

PMID- 16911098
TI  - Influence of residual bacteria on periapical tissue healing after chemomechanical
      treatment and root filling of experimentally infected monkey teeth.
AB  - The purpose of this study was twofold: first, to determine the influence on the
      healing of the periapical tissues when selected bacterial strains and
      combinations thereof remain after root canal treatment; and, second, the
      relationship to healing of the quality of the root filling. In eight monkeys, 175
      root canals, previously infected with combinations of four or five bacterial
      strains and with radiographically verified apical periodontitis, were
      endodontically treated, bacteriologically controlled, and permanently obturated.
      After 2-2.5 yr, the periapical regions were radiographically and histologically
      examined. Of these teeth, 48 root canals were also examined for bacteria
      remaining after removal of the root fillings. When bacteria remained after the
      endodontic treatment, 79% of the root canals showed non-healed periapical
      lesions, compared with 28% where no bacteria were found. Combinations of residual
      bacterial species were more frequently related to non-healed lesions than were
      single strains. When no bacteria remained, healing occurred independently of the
      quality of the root filling. In contrast, when bacteria remained, there was a
      greater correlation with non-healing in poor-quality root fillings than in
      technically well-performed fillings. In root canals where bacteria were found
      after removal of the root filling, 97% had not healed, compared with 18% for
      those root canals with no bacteria detected. The present study demonstrates the
      importance of obtaining a bacteria-free root canal system before permanent root
      filling in order to achieve optimal healing conditions for the periapical
      tissues.

PMID- 16911099
TI  - Psychological trauma exposure and trauma symptoms among individuals with high and
      low levels of dental anxiety.
AB  - This questionnaire-based study investigated the traumatic background and trauma
      related symptomatology among 141 treatment-seeking individuals with high levels
      of dental anxiety and among a low-anxious reference group consisting of 99
      regular dental patients. The highly anxious individuals reported a significantly
      higher number of traumatic events, both within and outside the dental or medical
      setting, than those in the reference group (73% vs. 21%). Horrific experiences in
      the dental setting were the most common traumatic events reported. Of the highly
      anxious individuals, 46.1% indicated suffering from one or more of the post
      traumatic stress disorder (PTSD) symptom clusters (re-experiencing, avoidance,
      loss of interest, and insomnia), while in the reference group this percentage was
      6%. Severity of dental anxiety was significantly associated with number of
      screening criteria for specific phobia and the extent to which the anxious
      subjects displayed symptoms of post-traumatic stress. Two variables were uniquely
      predictive for positive diagnostic screens for dental phobia and PTSD: having
      experienced a horrific dental treatment and having been a victim of a violent
      crime. In conclusion, post-traumatic symptoms are common accompaniments of severe
      forms of dental anxiety and are experienced even when dental treatment is not
      imminent.

PMID- 16911100
TI  - Combining paracetamol with a selective cyclooxygenase-2 inhibitor for acute pain
      relief after third molar surgery: a randomized, double-blind, placebo-controlled
      study.
AB  - Severe pain after third molar surgery is often encountered and more effective
      treatment regimes are warranted. The objective of this study was to evaluate if
      the combination of paracetamol and rofecoxib, a selective cyclooxygenase-2 (COX
      2) inhibitor, improves analgesic effects following third molar surgery compared
      with rofecoxib alone. Paracetamol alone was also evaluated. Altogether 120
      patients with moderate to severe pain after third molar surgery were given a
      single postoperative dose of one of the following treatments: rofecoxib +
      paracetamol; rofecoxib alone; paracetamol alone; or placebo. Patients assessed
      level of pain and pain relief every 30 min for 8 h after surgery, and made a
      global evaluation of the medication 4 and 8 h after surgery. Paracetamol and
      rofecoxib combined improved the analgesic effect compared with rofecoxib alone
      for the first 1.5 h. Rofecoxib alone and the combination of paracetamol and
      rofecoxib had a significantly better analgesic effect than paracetamol alone from
      3 h onwards. The early onset of pain relief for the combination of paracetamol
      and rofecoxib, compared with rofecoxib alone, could be of great importance when
      treating acute pain after third molar surgery. After data collection for this
      study, rofecoxib was withdrawn from the market as a result of reported fatal
      cardiovascular events. Whether this is relevant for short-term use is unknown,
      but it has to be considered before rofecoxib may be used for pain relief
      following third molar surgery.

PMID- 16911101
TI  - The relationship between the termination of cell proliferation and expression of
      heat-shock protein-25 in the rat developing tooth germ.
AB  - Odontoblast- and ameloblast-lineage cells acquire heat-shock protein (HSP)-25
      immunoreactivity after they complete cell division during postnatal odontogenesis
      in rat molars. However, there are no data available concerning the relationship
      between the termination of cell proliferation and HSP-25 immunoreactivity during
      tooth morphogenesis. We compared the expression of HSP-25 in tooth germs with
      their proliferative activity in the rat prenatal to perinatal molar and postnatal
      incisor to clarify the functional significance of HSP-25 during tooth
      morphogenesis by immunohistochemistry using anti-HSP-25 and anti-Ki67/5-bromo-2'
      deoxyuridine (BrdU). Numerous proliferating cells in developing molars were
      distributed throughout the tooth germ and HSP-25 immunoreactivity was
      recognizable in the dental epithelial and mesenchymal cells after they completed
      cell division. However, both cell proliferation and immunoreaction for HSP-25 are
      absent in the enamel knots. The distribution pattern of the proliferating cells
      in the incisors was basically identical to that in the prenatal molars except for
      the lack of non-proliferating secondary enamel knots and the sparse distribution
      of proliferating cells in the apical bud. Thus, HSP-25 protein is suggested to
      act as a switch between cell proliferation and terminal cyto-differentiation
      during odontogenesis.

PMID- 16911102
TI  - Cell proliferation in teeth reconstructed from dispersed cells of embryonic tooth
      germs in a three-dimensional scaffold.
AB  - Tissue engineering can now reproduce tooth from postnatal tooth cells. However,
      crown formation is not accurately reconstituted, even when the complex structure
      of the enamel dentin is reproduced. Here, we showed that a tissue-engineered (TE)
      tooth, exhibiting morphogenesis according to regular crown-cusp pattern
      formation, was produced by embryonic tooth germ cells in a three-dimensional
      scaffold. Heterogeneous cells dissociated from embryonic day 14 (E14) mice tooth
      germs were seeded on a scaffold and implanted under a kidney capsule in adult
      mice. The developmental process of the implants was examined for up to 14 d. At 5
      d, the cells had formed initial tooth germ, followed by enamel-covered dentin
      tissue formed symmetrically. To study the developmental process, we examined the
      growth pattern using 5-bromo-2'-deoxyuridine (BrdU)-labeling analysis. The
      initial cell-proliferation patterns of the TE teeth were similar to that at the
      cap and early bell stages in natural teeth. This was particularly true in the
      cervical loop, which showed a similar distribution pattern of BrdU-positive cells
      in TE- and natural teeth. These results suggested that even when embryonic tooth
      germs are dissociated, the single cells can reconstitute tooth, and that enamel
      organ morphogenesis proceeds as in natural teeth.

PMID- 16911103
TI  - Insulin-like growth factor system components in the periodontium during tooth
      root resorption and early repair processes in the rat.
AB  - There is evidence that growth factors, such as the insulin-like growth factors
      (IGFs), are involved in biological and pathological processes in oro-dento-facial
      tissues. To investigate their roles in tooth movement, root resorption, and
      repair, the occurrence of components of the IGF system, including the ligands IGF
      I and -II, the IGF receptor 1 (IGF1R) and six IGF-binding proteins (IGFBP-1 to 
      6), was investigated by immunohistochemistry on sections from rat maxillae where
      the first molar had been moved mesially by means of an orthodontic appliance for
      9 d to induce root resorption. After force deactivation on day 0, early repair
      was studied after a further 5, 7, 10, 12, 14, and 17 d. The immunostaining
      pattern in the periodontal ligament, cementum, and bone of control animals showed
      similarities known from studies in human teeth. Increased immunostaining for
      nearly all components in pressure sides and resorption lacunae indicated an
      involvement in resorption processes and clastic activities. During early stages
      of repair, the occurrence of several components (e.g. IGF-II, IGFBP-5 or -6)
      within lacunae and in cementoblasts showed an involvement in the resorption
      repair sequence, which is considered to be a coupling process as known from bone.

PMID- 16911105
TI  - Adsorption of chlorhexidine and black tea onto in vitro salivary pellicles, as
      studied by ellipsometry.
AB  - The adsorption from 0.2% (w/w) chlorhexidine and black tea solutions onto an in
      vitro pellicle from whole unstimulated saliva on hydroxyapatite discs was studied
      by ellipsometry. It was found that chlorhexidine adsorbed to the pellicle and
      caused a modification of the pellicle properties, leading to a subsequent
      increase in adsorption of salivary and black tea components. There was a distinct
      order-of-addition effect, whereby chlorhexidine followed by black tea gave an
      overall greater adsorption of components compared with black tea followed by
      chlorhexidine. This increase in adsorption resulted in a concomitant increase in
      color or stain, as measured by a reflectance chromameter. The increase in
      adsorbed amounts and stain was modified, in part, by the adsorption of salivary
      fractions between the chlorhexidine and black tea treatments. In all cases, the
      chlorhexidine and black tea-modified pellicles were not readily removed by either
      phosphate or sodium dodecyl sulfate rinses. Thus, following exposure to
      chlorhexidine, the accelerated adsorption of salivary and black tea components
      can ultimately lead to increased staining of the pellicle.

PMID- 16911104
TI  - Influence of testosterone on gene expression in the ovariectomized mouse
      submandibular gland.
AB  - Androgens exert significant effects on the murine submandibular gland. Our
      objective in this study was to determine the nature and extent of testosterone
      regulation of gene expression in the female submandibular gland, and to explore
      the degree to which this control is the same as in male glands. Ovariectomized
      female BALB/c mice were treated with placebo- or testosterone-containing hormone
      pellets for 14 d. Glands were collected and total RNA was isolated. Samples were
      analyzed for differential expression of mRNA using CodeLink microarrays, and the
      data were evaluated using genesifter. Testosterone significantly influenced the
      expression of over 500 genes, and while many (n = 214) of the genes were
      similarly differentially expressed in androgen-treated males, there were also
      many that were unique. These findings support our hypotheses that testosterone
      extensively influences gene expression in the female submandibular gland, and
      that the nature of this influence is variable between sexes.

PMID- 16911106
TI  - The effect of cocoa polyphenols on the growth, metabolism, and biofilm formation
      by Streptococcus mutans and Streptococcus sanguinis.
AB  - The aim of this study was to determine if cocoa polyphenols could interfere with
      biofilm formation by Streptococcus mutans or Streptococcus sanguinis, and reduce
      acid production from sucrose by S. mutans. The antimicrobial activity of cocoa
      polyphenols was assessed against cariogenic (S. mutans) and health-associated (S.
      sanguinis) species by minimum inhibitory concentration assays. Cocoa polyphenol
      dimer, tetramer, and pentamer inhibited the growth of S. sanguinis, whereas the
      growth of S. mutans was unaffected. However, pretreatment of surfaces with cocoa
      polyphenol pentamer (35 microM) reduced biofilm formation by S. mutans at 4 and
      24 h, whereas the effects on S. sanguinis were less consistent. In contrast,
      brief exposure of preformed biofilms to pentamer either had no significant effect
      or resulted in increased counts of S. mutans under certain conditions. Cocoa
      polyphenol pentamer (500 microM) significantly reduced the terminal pH, and
      inhibited the rate of acid production by S. mutans at pH 7.0. In conclusion,
      cocoa polyphenols can reduce biofilm formation by S. mutans and S. sanguinis, and
      inhibit acid production by S. mutans.

PMID- 16911107
TI  - Antibacterial effect of an ozone device and its comparison with two dentin
      bonding systems.
AB  - Microorganisms remaining beneath restorations can cause secondary caries and pulp
      damage. Because of this, antimicrobial treatment could be useful. The aim of this
      study was to evaluate the antibacterial effect of the HealOzone device on
      Streptococcus mutans and to compare it with the already proven activity of two
      dentin-bonding systems. Thirty-five human molars were divided into 5 groups.
      Cavities were then cut into the teeth (n = 28 cavities per group). After
      sterilization, the teeth were left in broth cultures of 10(6) colony-forming
      units (CFU) ml(-1) of S. mutans at 36 degrees C for 48 h. The appropriate
      treatment followed (group A, control; group B, Clearfil SE Bond; group C,
      Clearfil Protect Bond; group D, 40 s of treatment with ozone; and group E, 80 s
      of treatment with ozone), and the cavities were then filled with composite resin.
      After 72 h, the restorations were removed, dentin chips were collected with an
      excavator, and the total number of microorganisms was determined. All treatments
      significantly reduced the number of S. mutans present compared with the control
      group. The antimicrobial effect of both bonding systems and treatment with 80 s
      of ozone was significantly higher than the 40 s ozone treatment. In conclusion,
      HealOzone and the bonding systems show striking antimicrobial effects against S.
      mutans.

PMID- 16911108
TI  - Spectroscopic investigation of the function of aqueous 2
      hydroxyethylmethacrylate/glutaraldehyde solution as a dentin desensitizer.
AB  - Fourier-transform (FT)-Raman and -infrared (IR) spectroscopy were employed to
      investigate the function of the aqueous 2-hydroxyethylmethacrylate/glutaraldehyde
      solution (Gluma) as a desensitizer. 2-Hydroxyethylmethacrylate (HEMA),
      glutaraldehyde (GA), and the mixture of HEMA/GA (i.e. Gluma) were used to
      interact with dentin, collagen, hydroxyapatite (HAP), and bovine serum albumin
      (BSA) individually. All the interactions were monitored by an FT-Raman
      spectrometer. FT-IR spectroscopy was also used in this study. The results show
      that HEMA could be absorbed by dentin and collagen; GA could cross-link collagen
      and BSA; and when BSA was added to Gluma, polymerization of HEMA occurred. The
      results suggest that Gluma acts as a desensitizer whereby, first, GA reacts with
      part of the serum albumin in dentinal fluid, which induces a precipitation of
      serum albumin, then, second, a reaction of GA with serum albumin induces
      polymerization of HEMA. The function of Gluma as a desensitizer to block dentinal
      tubules occurs via these two reactions.

PMID- 16911109
TI  - Considering older cats.

PMID- 16911110
TI  - Prospective open pilot study on the use of ciclosporin for feline allergic skin
      disease.
AB  - OBJECTIVES: To evaluate the efficacy of ciclosporin in cats with allergic skin
      disease. METHODS: Ten cats with signs of allergic skin disease were administered
      ciclosporin daily at a dose of 3.6 to 8.3 mg/kg for one month. None of these cats
      had previously responded to a hypoallergenic diet trial, and all animals had
      previously been treated with endectoparasiticidal drugs, with no improvement two
      weeks before entering the trial. On days 0 and 30, owners assessed pruritus with
      a visual analogue scale, and veterinarians evaluated cutaneous lesions. RESULTS:
      All the cats had pruritus and erythema, five had alopecia, two had an
      eosinophilic plaque, one had miliary dermatitis and two had both alopecia and an
      eosinophilic plaque. Good or excellent improvement was observed in 40 per cent of
      cats for pruritus, 57 per cent of cats for alopecia and 60 per cent of cats for
      erythema. A significant decrease in mean scores was observed for pruritus only,
      while for erythema and alopecia, it was close to being significant (P < 0.052).
      CLINICAL SIGNIFICANCE: Ciclosporin may be helpful in symptomatically treating
      signs of feline allergic skin disease. However, it is important to remember that
      ciclosporin is not licensed for use in cats.

PMID- 16911111
TI  - Feline osteoarthritis: a prospective study of 28 cases.
AB  - OBJECTIVES: To identify a cohort of cats with clinical osteoarthritis and to
      report on the clinical signs, the frequency of joints affected and the possible
      aetiopathogenesis within this population. METHODS: Inclusion criteria for this
      prospective study were presence of historical evidence and/or clinical signs of
      osteoarthritis, together with radiographic evidence of osteoarthritis. Patients
      showed clinical improvement within four weeks of analgesic administration and
      were free from other disease processes, which might explain the clinical signs
      and/or their response to analgesia. RESULTS: Twenty-eight cases were included in
      the cohort. The elbow (45 per cent) and the hip (38 per cent) were the most
      frequently affected joints. Seventy-one per cent of cases had primary/idiopathic
      aetiology. Alterations in both the ability to jump (71 per cent) and the height
      (67 per cent) of jump (lifestyle changes) were the most frequent signs of
      disease. Sixty-one per cent of owners felt that their pet had made a marked
      improvement following administration of an analgesic/anti-inflammatory drug.
      There were statistically significant improvements in the ability to jump (P <
      0.001), the height of jump (P < 0.001), lameness (P = 0.03), stiff gait (P =
      0.04) and the activity level (P = 0.02) when compared with the start and the end
      of the study period. CLINICAL SIGNIFICANCE: Osteoarthritis is a clinical problem
      in cats, but overt lameness is not the most common clinical feature.

PMID- 16911112
TI  - Association of laboratory data and death within one month in cats with chronic
      renal failure.
AB  - OBJECTIVES: To retrospectively compare the data taken at the first visit of 34
      cats with chronic renal failure surviving more than one month (surviving group)
      and 16 cats dying within one month (non-surviving group). METHODS: Records were
      collected on cats with chronic renal failure presented to a private veterinary
      practice in Nagoya, Japan, from March 1996 to March 2005. All cats with chronic
      renal failure diagnosed on the basis of case histories, clinical signs (such as,
      lethargy, anorexia, loss of bodyweight and vomiting) and a high plasma creatinine
      (>180 micromol/l) were included in the study. RESULTS: Plasma creatinine, urea
      nitrogen, inorganic phosphate, packed cell volume and urine protein/creatinine
      ratio were significantly different between cats of the surviving and non
      surviving groups. In the surviving group, survival statuses were recorded, and
      laboratory data was obtained within one month before death in 13 cats. In the 13
      cats, plasma creatinine, packed cell volume and urine protein/creatinine ratio
      showed significant differences between the data taken within one month before
      death and that taken at first visit, and only urine protein/creatinine ratio
      exhibited a consistent alteration (increase) in relation to first visit data.
      CLINICAL SIGNIFICANCE: These results indicated that plasma creatinine, urea
      nitrogen, inorganic phosphate, packed cell volume and urine protein/creatinine
      ratio were associated with death within one month and urine protein/creatinine
      ratio was most likely to be associated with mortality in cats with chronic renal
      failure.

PMID- 16911113
TI  - Ixodes frontalis and avian tick-related syndrome in the United Kingdom.
AB  - OBJECTIVES: This study aimed to characterise tick species responsible for avian
      tick infestations in the UK, to analyse various risk factors for tick-related
      syndrome in tick-infested birds and to test samples for the presence of certain
      tick-transmitted pathogens. METHODS: Ticks, blood, splenic tissue and tick
      attachment site tissue from birds with attached ticks were requested from
      veterinarians and wildlife sanctuaries around the UK. Ticks were identified
      according to standard keys, and samples were analysed via DNA PCR test for
      Borrelia burgdorferi sensu lato, Babesia species, Bartonella species and
      Ehrlichia species. RESULTS: Ixodes frontalis was the most commonly identified
      tick, and an association of adult female I frontalis with tick-related syndrome
      in birds was demonstrated. Tick infestation was markedly seasonal. I frontalis
      was found on 32 species of birds. DNA PCR testing was uniformly negative. Of the
      birds known to have been treated, 75 per cent (nine of 12) survived. CLINICAL
      SIGNIFICANCE: Tick-related syndrome is a poorly understood syndrome, with
      sporadic distribution, both geographically and seasonally. This study confirms I
      frontalis as the most common cause of this syndrome in the UK and identifies some
      features of the tick life cycle in this country. The benefit of treatment in
      affected birds is highlighted. Risk factors for tick-related syndrome are
      examined and preventive strategies discussed.

PMID- 16911114
TI  - Primary uterine inertia in 27 bitches: aetiology and treatment.
AB  - OBJECTIVES: To evaluate two treatment methods in bitches with primary uterine
      inertia in relation to blood concentrations of oxytocin, calcium and glucose.
      METHODS: A prospective study where 27 bitches with primary inertia were randomly
      allocated to treatment groups I and II. Blood samples were collected before and
      after treatment. Group I was treated with a combination of intravenous calcium
      solutions and oxytocin and group II with oxytocin only. If unsuccessful,
      caesarean sections or additional medical treatment was pursued. RESULTS: Plasma
      oxytocin concentrations were 35+/-15 pmol/l in group I and 30+/-15 pmol/l in
      group II. Before treatment, the total serum calcium concentrations were 2.1+/-0.2
      mmol/l in both the groups, and blood glucose values were 7.0+/-0.5 mmol/l (group
      I) and 7.3+/-1.4 mmol/l (group II). The number of bitches subjected to caesarean
      sections and the number of puppies born did not differ between the two groups.
      CLINICAL SIGNIFICANCE: This study indicates that low plasma oxytocin levels is a
      cause of primary inertia in bitches with normal serum calcium concentrations and
      aggravates the condition in bitches with low calcium levels. Hypoglycaemia was
      not observed. The outcome of labour did not differ between groups I and II.

PMID- 16911116
TI  - Lomustine for the treatment of gastrointestinal mast cell tumour in a dog.
AB  - An eight-year-old, male boxer dog was referred for the treatment of a large (5.5
      x 5 cm), unresectable visceral mast cell tumour. The dog had a surgical resection
      performed one month before referral, and it had widespread metastases to the
      abdominal lymph nodes. The patient was treated with lomustine and prednisone and
      showed a rapid improvement and increased level of activity, weight gain and
      consistent tumour reduction. The patient remained in partial remission (defined
      as a greater than 50 per cent reduction in tumour volume) for seven months.
      Toxicity was acceptable and was limited to moderate anaemia and two episodes of
      neutropenia. At the completion of the seven months of therapy, the dog
      experienced a chemotherapy-induced sepsis, and the owners elected for euthanasia
      due to financial concerns. At that time, the tumour was still in partial
      remission. This case report suggests that a combination of lomustine and
      prednisone is an effective protocol for the palliation of aggressive visceral
      mast cell tumours.

PMID- 16911115
TI  - Dynamic tracheal collapse associated with disseminated histiocytic sarcoma in a
      cat.
AB  - This case report describes an unusual presentation of histiocytic sarcoma in a
      domestic shorthair cat. Initial investigation revealed a haemodynamically
      insignificant hypertrophic cardiomyopathy, bronchitis and a mild irregularity of
      the cervical trachea. The cat's disease progressed over a two-week period. Repeat
      radiography and tracheoscopy revealed a marked dynamic tracheal collapse
      associated with a raised plaque-like lesion within the cervical trachea.
      Subsequent post-mortem examination and histopathology revealed disseminated
      histiocytic sarcoma involving the trachea and kidneys. This is the first reported
      case of a histiocytic sarcoma involving the trachea in either dogs or cats.

PMID- 16911117
TI  - Torsion and volvulus of the transverse and descending colon in a German shepherd
      dog.
AB  - A German shepherd dog was presented two months after surgery for correction of
      acute gastric dilatation volvulus. The dog had been diagnosed with exocrine
      pancreatic insufficiency. Radiographs revealed marked gaseous distension of one
      loop of intestine with a generalised increase in intestinal gas content. A 360
      degrees anticlockwise rotation of the descending and transverse colon, around the
      longitudinal axis of the mesocolon, was diagnosed at exploratory coeliotomy. The
      transverse and descending colon appeared uniformly necrotic and an end-to-end
      colo-colic resection and anastomosis was performed. The dog initially made
      satisfactory postoperative progress but was euthanased on the third postoperative
      day after it developed an intestinal intussusception.

PMID- 16911118
TI  - Idiopathic megaoesophagus and intermittent gastro-oesophageal intussusception in
      a cat.
AB  - An eight-month-old domestic shorthair cat was presented with chronic vomiting for
      three months, with an acute increase in frequency during the past two days. A
      diagnosis of megaoesophagus was made by chest radiography. Diagnostic work-up for
      megaoesophagus was performed. A gastro-oesophageal intussusception was identified
      during endoscopy. Medical and nutritional therapy was instituted with a good
      response to the treatment.

PMID- 16911119
TI  - Mycoplasma felis arthritis in two cats.
AB  - This report describes the occurrence of non-weightbearing lameness caused by
      Mycoplasma felis monoarthritis in two, immunocompetent, European, shorthair adult
      cats with a suspected history of trauma. Clinical signs recurred after
      conservative treatment. The joints were treated surgically and M felis was
      identified as the causative agent for the monoarthritis. Medication with 10 mg/kg
      doxycycline twice daily was initiated according to susceptibility testing. One
      cat underwent further joint flushing after two weeks; both the cats recovered
      completely after eight and nine weeks, respectively. The findings suggest that M
      felis, in addition to being an agent associated with conjunctivitis in cats, is
      able to act as a pathogen in other tissues and cause arthritis even in
      immunocompetent cats.

PMID- 16911120
TI  - Congestive heart failure caused by intracardiac tumours in two dogs.
AB  - Congestive heart failure is a common presentation in small animal practice.
      Cardiac tumours are an unusual cause of congestive heart failure and, when they
      occur, usually cause clinical signs associated with pericardial effusion and
      cardiac tamponade. This case report outlines the clinical and histological
      findings in two dogs presented with clinical signs of congestive heart failure
      caused by obstruction of blood flow by intracavitary cardiac tumours. Case 1
      showed signs of left-sided heart failure caused by osteosarcoma within the left
      atrial lumen, and case 2 presented with clinical signs of right-sided heart
      failure due to haemangiosarcoma occupying the right atrial and ventricular
      lumens. This case report provides further evidence for the inclusion of
      intracardiac neoplasia in the differential diagnosis for dogs with clinical signs
      of congestive heart failure.

PMID- 16911121
TI  - What is your diagnosis? Mycobacterial infection.

PMID- 16911122
TI  - Evaluation of the KA24 (Knowledge Access 24) service for health and social care
      staff in London and the south-east of England. Part 2: qualitative.
AB  - AIM AND OBJECTIVES: The aim of this two-part paper is to identify the main
      transferable lessons learned from both the quantitative and qualitative
      evaluations of the KA24 (Knowledge Access 24) service of online databases and
      selected full-text journals for health and social care staff in London and the
      south-east of England. The objectives of the qualitative evaluation were to
      assess the enablers and barriers to usage, and to assess the impact of the
      service on patient care. METHODS: Telephone interviews (n = 65) and a
      questionnaire survey (n = 296) were conducted with various types of user, in
      various Trust settings. Some non-users were also contacted. Selection of
      interviewees and questionnaire recipients was not random, and aimed to cover all
      groups of users representatively. RESULTS: Results show that policy goals were
      being delivered, with indications of changes to clinical practice, and improved
      clinical governance. Promotion, training and support needs to be extensive, and
      tailored to needs, but users are not always aware they need training. The sharing
      of passwords cast doubts on the reliability of some usage data. CONCLUSIONS:
      Digital health library services, delivered at the point of care, are changing the
      way some clinicians practise. A combination of qualitative and quantitative
      evaluation methods are needed to assess digital library services.

PMID- 16911123
TI  - Euroethics--a database network on biomedical ethics.
AB  - BACKGROUND: EUROETHICS is a database covering European literature on ethics in
      medicine. It is produced within Eurethnet, a European information network on
      ethics in medicine and biotechnology. OBJECTIVES: The aim of Euroethics is to
      disseminate information on European bioethical literature that may otherwise be
      difficult to find. METHODS: A collaboration model for pooling data from different
      centres was developed. The policy was to accomplish data uniformity, while still
      allowing for local differences in terms of software, indexing practices and
      resources. Records contributed to the database follow common standards in terms
      of data fields and indexing terms. The indexing terms derive from two thesauri,
      Thesaurus Ethics in the Life Sciences (TELS) and Medical Subject Headings (MeSH).
      Combining elements from search tools developed previously, the developers sought
      to find a technical solution optimized for this data model. An approach relying
      on a thesaurus database that is loaded along with the bibliographic database is
      described. RESULTS AND CONCLUSIONS: The present case study offers examples of
      possible approaches to several tasks often encountered in database development,
      such as: merging data from diverse sources, getting the most out of indexing
      terms used in a database, and handling more than one thesaurus in the same
      system.

PMID- 16911124
TI  - Collection policy management for the Kuopio University and Kuopio University
      Hospital, Finland: detecting the needs of users and developing high-quality
      collections.
AB  - BACKGROUND: This article discusses the collection policies of a university
      library in a modern digital environment. A brief description of national
      collection policy decisions in Finland is provided. The rapid evolution and
      growth of scientific publication places new demands on building a collection in a
      health and bioscience orientated university, and it requires an evidence-based
      approach to support effective service processes. OBJECTIVES: The aim of the study
      was to identify the needs of the university's students and staff. METHODS: Usage
      statistics were surveyed and analysed. RESULTS: Both usage statistics and user
      surveys indicate that the library use is divided half-and-half between the
      traditional use of printed material and library premises and the modern use of
      digital materials via the Web. The former is mainly the way that the students and
      hospital staff use the library, and the latter can be viewed as the researchers'
      way of using the library. Librarians and information specialists act in this as
      service providers and/or guides and tutors to the end-users. These results,
      however, must be validated with a longer timescale data collation and analysis,
      both of which are an ongoing process within the library. CONCLUSIONS: It is
      important that requirements and needs of the library's users are monitored
      regularly and acquisition policies are updated frequently. It also seems that the
      needs have changed quite dramatically in response to modern ways of disseminating
      publications, but this supposition will require further study.

PMID- 16911125
TI  - Learning to use the Internet as a study tool: a review of available resources and
      exploration of students' priorities.
AB  - BACKGROUND: The Internet is a valuable information tool, but users often struggle
      to locate good quality information from within the vast amount of information
      available. OBJECTIVE: The aim of the study was to identify the online information
      resources available to assist students develop Internet searching skills, and to
      explore the students' priorities in online guides. METHODS: A qualitative
      approach was adopted with two phases. The first was a structured search of
      available online study skills resources. The second comprised 10 group interviews
      with a total of 60 students at all stages of five undergraduate health and social
      care related courses at a UK university. RESULTS: The study found that there were
      good online guides available, but that, perversely, the better guides tended to
      require the best searching skills to locate them. A few students were
      enthusiastic about using online support, however the majority felt that if they
      had the skills to locate such resources they wouldn't use a study guide to
      improve these skills, and if they did not have the skills they would not think of
      using an online guide to develop them. CONCLUSIONS: Students wanted assistance
      when they had problems or questions, rather than sites that offered structured
      learning experiences. Personal support rather than virtual support was also
      considered to be most important to the students in this study.

PMID- 16911126
TI  - Open access publishing in the biomedical sciences: could funding agencies
      accelerate the inevitable changes?
AB  - BACKGROUND: Open access is making a noticeable impact on access to information.
      In 2005, many major research funders, including the Wellcome Trust, National
      Institutes for Health (NIH), and the Research Councils UK (RCUK), set out their
      position in a number of statements. Of particular note was the stipulation that
      authors receiving grants must deposit their final manuscript in an open access
      forum within 6-12 months of publication. OBSERVATIONS: The paper will look at the
      open access position statements issued by some of the major funding bodies in the
      biomedical sciences. The paper will also look at the models used by publishers to
      provide open or delayed access, such as Oxford Open from Oxford University Press,
      HighWire Press' delayed access policy, BioMed Central, and Public Library of
      Science (PLoS). There are now over 1.2 million articles in PubMed that are freely
      accessible via publishers' websites.(1) CONCLUSION/DISCUSSION: Could funding
      agencies accelerate the move to open access? The list of funding agencies
      supporting open access is growing. The National Institutes for Health and the
      Wellcome Trust have been joined by many of the world's major funders in
      biomedical research whose goal it is to make their research findings available
      with no barriers.

PMID- 16911127
TI  - Map of dermatology: 'first-impression' user feedback and agenda for further
      development.
AB  - BACKGROUND: Map of Dermatology (http://healthcybermap.org/dermap/) is a free web
      resource that enables users to search for images of skin conditions by body
      region and morphology rather than by condition name, which is much more useful
      and natural in answering questions about unknown clinical
      presentations/diagnoses, especially for non-specialists. OBJECTIVES AND METHODS:
      This paper presents responses received from twelve users, including specialist
      dermatologists, non-specialists (some with interests in health informatics), and
      lay persons, who provided their 'first-impression' feedback on Map of Dermatology
      by responding to a very short e-mail questionnaire covering service usefulness
      and interface usability. The paper also provides a brief review of the gaps in
      current online dermatology information service provision in general. RESULTS: The
      overall user feedback received was very positive. An exploratory discussion of
      the arguments and possibilities for radically improving Map of Dermatology to
      produce 'the ultimate web-based dermatology diagnostic tool' is also provided,
      together with some desiderata and preliminary 'design and feature specifications'
      for such a tool based on users' suggestions, the gaps highlighted in other
      existing online dermatology tools, and the author's own reflections and
      experience. CONCLUSIONS: When successfully developed, the proposed tool is
      expected to have significant potential for efficiently and effectively addressing
      many of the currently unmet educational needs of clinicians.

PMID- 16911128
TI  - Do financial factors such as author page charges and industry funding impact on
      the nature of published research in infectious diseases?
AB  - OBJECTIVES: The question of who pays for research to be conducted and published
      is an important one as it may result in publication bias. The traditional model
      of medical publishing has relied on subscriptions for funding. There has been
      increasing interest in making the results of scientific research freely
      available. One proposed mechanism is an author-pays system, which shifts cost
      from subscribers to authors. We investigated the impact of author page charges on
      the nature and type of published research, and the association of industry
      funding with types of published research. METHODS: Four infectious diseases
      journals with comparable scope were studied-two with page charges and two
      without. Variables included type of research study, area of research, author
      demographics, study setting and industry funding. The differences between a
      subscription model vs. a mixed model (author page charges and subscription
      charges) were studied. We also investigated changes within the same journal once
      it had moved from a subscription model to a mixed model. RESULTS: Authors from
      developing countries were significantly less likely to be published in the mixed
      model journals (OR 0.25, 95% CI 0.15-0.41, P < 0.001). Clinical trials published
      in any type of journal were significantly more likely to be industry funded than
      any other type of research (OR 12.7, 95% CI 7.0-22.9, P < 0.001). Industry-funded
      research was significantly less likely to be about diseases affecting
      predominantly the developing world (OR 0.47, 95% CI 0.25-0.89, P < 0.05).
      CONCLUSION: There is clearly a relationship between industry funding and certain
      types of published research. The model of funding of journal publishing can also
      affect the nature of published research. Shifting publishing costs to authors
      favours well-funded organizations, industry sponsored research and wealthy
      countries. Such potential for publication bias must be considered when planning
      for open access models.

PMID- 16911129
TI  - How to provide an alerting service on health topics for medical journalists
      selecting papers from scientific journals.

PMID- 16911130
TI  - The number needed to retrieve: a practically useful measure of information
      retrieval?

PMID- 16911134
TI  - Patient safety: what role can patients play?

PMID- 16911135
TI  - What choices should we be able to make about designer babies? A Citizens' Jury of
      young people in South Wales.
AB  - BACKGROUND: Young people will increasingly have the option of using new
      technologies for reproductive decision making but their voices are rarely heard
      in debates about acceptable public policy in this area. Capturing the views of
      young people about potentially esoteric topics, such as genetics, is difficult
      and methodologically challenging. DESIGN: A Citizens' Jury is a deliberative
      process that presents a question to a group of ordinary people, allows them to
      examine evidence given by expert witnesses and personal testimonies and arrive at
      a verdict. This Citizens' Jury explored designer babies in relation to inherited
      conditions, saviour siblings and sex selection with young people. PARTICIPANTS:
      Fourteen young people aged 16-19 in Wales. RESULTS: Acceptance of designer baby
      technology was purpose-specific; it was perceived by participants to be
      acceptable for preventing inherited conditions and to create a child to save a
      sibling, but was not recommended for sex selection. Jurors stated that permission
      should not depend on parents' age, although some measure of suitability should be
      assessed. Preventing potential parents from going abroad was considered
      impractical. These young people felt the Human Fertilisation and Embryology
      Authority should have members under 20 and that the term 'designer baby' was not
      useful. CONCLUSIONS: Perspectives on the acceptability of this technology were
      nuanced, and based on implicit value judgements about the extent of individual
      benefit derived. Young people have valuable and interesting contributions to make
      to the debate about genetics and reproductive decision making and a variety of
      innovative methods must be used to secure their involvement in decision-making
      processes.

PMID- 16911136
TI  - Preliminary testing of a just-in-time, user-defined values clarification exercise
      to aid lower literate women in making informed breast cancer treatment decisions.
AB  - OBJECTIVE: To report on the initial testing of a values clarification exercise
      utilizing a jewellery box within a computerized patient decision aid (CPtDA)
      designed to assist women in making a surgical breast cancer treatment decision.
      DESIGN: Pre-post design, with patients interviewed after diagnosis, and then
      after completing the CPtDA sometime later at their preoperative visit. SAMPLE:
      Fifty-one female patients, who are low literate and naive computer users, newly
      diagnosed with early stage breast cancer from two urban public hospitals.
      INTERVENTION: A computerized decision aid that combines entertainment-education
      (edutainment) with enhanced (factual) content. An interactive jewellery box is
      featured to assist women in: (1) recording and reflecting over issues of concern
      with possible treatments, (2) deliberating over surgery decision, and (3)
      communicating with physician and significant others. OUTCOMES: Patients' use of
      the jewellery box to store issues during completion of the CPtDA, and perceived
      clarity of values in making a treatment decision, as measured by a low literacy
      version of the Decisional Conflict Scale (DCS). RESULTS: Over half of the
      participants utilized the jewellery box to store issues they found concerning
      about the treatments. On average, users flagged over 13 issues of concern with
      the treatments. Scores on the DCS Uncertainty and Feeling Unclear about Values
      subscales were lower after the intervention compared to before the decision was
      made. CONCLUSIONS: A values clarification exercise using an interactive jewellery
      box may be a promising method for promoting informed treatment decision making by
      low literacy breast cancer patients.

PMID- 16911137
TI  - Decision aids for familial breast cancer: exploring women's views using focus
      groups.
AB  - BACKGROUND: There is increasing need for accessible information about familial
      breast cancer for those facing complex decisions around genetic testing,
      screening and treatment. Information currently includes leaflets and computerized
      decision aids, offering interactive interfaces to clarify complex choices.
      OBJECTIVE: Exploration of users' views and reactions to three decision aids for
      genetic testing for breast cancer using focus groups. SETTING: A regional cancer
      genetics service in the UK. PARTICIPANTS: Women over 18 years of age who had been
      referred to Cancer Genetics Service for Wales (CGSW) and had received a risk
      assessment for familial breast cancer. METHODS: Qualitative study involving one
      pilot and six extended focus groups with 39 women at high, moderate and
      population risk. Two CD-ROMs and one paper-based aid evaluated for: clarity of
      presentation, ease of handling, emotive response, increased knowledge and greater
      informed choice. RESULTS: Women reported variable preferences for different types
      of decision aids and mixed emotions, indicating the sensitivity of raising issues
      in decision support tools, lack of consensus over the most appropriate aid and no
      systematic differences between risk groups. Women remarked that aids increased
      their knowledge, particularly about breast cancer genes and risk and wanted a
      decision aid designed within the context of the NHS, in both paper-based and CD
      ROM formats from an authoritative source. Mixed views about presentation styles
      suggest decision aids would be most effective with a user-selected range of
      formats. CONCLUSIONS: Decision aid development should be informed by users and
      should meet the needs of those concerned about their risk of breast cancer in the
      UK. Without such aids, patients will continue to search for information from a
      variety of sources of varying quality.

PMID- 16911138
TI  - Predicting preferences: a neglected aspect of shared decision-making.
AB  - In recent years, shared decision-making between patients and doctors regarding
      choice of treatment has become an issue of priority. Although patients'
      preferences lie at the core of the literature on shared decision-making, there
      has not been any attempt so far to link the concept of shared decision-making
      with the extensive behavioural literature on people's self-predictions of their
      future preferences. The aim of the present review is to provide this link. First,
      we summarize behavioural research that suggests that people mispredict their
      future preferences and feelings. Secondly, we provide the main psychological
      accounts for people's mispredictions. Thirdly, we suggest three main empirical
      questions for inclusion in a programme aimed at enriching our understanding of
      shared decision-making and improving the procedures used for putting it into
      practice.

PMID- 16911139
TI  - Can I accurately predict the impact of an illness and its treatment on my future
      subjective well-being? A complex question that does not have a simple answer.

PMID- 16911140
TI  - Decision aids in routine practice: lessons from the breast cancer initiative.
AB  - BACKGROUND: Many decision aids have been developed to help patients make
      treatment and screening decisions; however, little is known about implementing
      them into routine clinical practice. OBJECTIVE: To assess the feasibility of
      implementing a patient decision aid (PtDA) for the early stage breast cancer
      surgical decision into routine clinical care. DESIGN: Structured individual
      interviews. SETTING AND PARTICIPANTS: A convenience sample of providers from nine
      sites, including two community resource centres, a community hospital and six
      academic centres. MAIN OUTCOME MEASURES: Usage data, barriers to and resources
      for implementing the PtDAs. RESULTS: Six of the nine sites were using the PtDAs
      with patients. Two sites were primarily using a scheduling system and four sites
      relied on a lending system. For the academic centres, the keys to successful
      implementation included integrating the PtDA into the flow of patients through
      the centre and having physicians who recommended it to patients. At the community
      centres, the keys to successful implementation included an informed staff and the
      flexibility to get the PtDAs to patients in different ways. Barriers that limited
      or prevented sites from using the PtDA included a lack of clinical support, a
      lack of system support, competing priorities and scheduling problems.
      CONCLUSIONS: It is feasible to implement a breast cancer PtDA into routine
      clinical care at academic centres and community resource centres. Future research
      should assess the effectiveness of PtDAs in routine clinical care as well as
      resources and barriers to their implementation in community hospitals.

PMID- 16911141
TI  - Development of an information source for patients and the public about general
      practice services: an action research study.
AB  - OBJECTIVE: The publication of information about the performance of health-care
      providers is regarded as central to promoting greater accountability and
      empowering patients to exercise choice. The evidence suggests that the public is
      not very interested in accessing or using current sources of information. This
      study aimed to explore the information needs of patients in the context of UK
      primary care and to develop an information source about general practice
      services, designed to be usable by and useful to patients. DESIGN: An action
      research study making use of data from formal and informal interviews, focus
      groups, participant observation and document review. SETTING: The geographical
      areas covered by two Primary Care Trusts in the north of England and two Local
      Health Boards in south Wales. PARTICIPANTS: A partnership between 103 members of
      the public, general practice staff from 19 practices, NHS managers from four
      Primary Care Organizations and the research team. RESULTS: The public would like
      to know more about the quality and range of general practice services but current
      sources of information do not meet their needs. The public do not like league
      tables comparing the performance of practices and only a small number of people
      want to use comparative information to choose between practices. They seem to be
      more interested in the context and availability of services and the willingness
      of practices to improve, than in the practice's absolute or relative performance.
      They want to be clear about the source of the information so that they can make
      personal judgements about its veracity. Information is most likely to be useful
      if it adheres to the basic principles of cognitive science in terms of its
      structure, content and presentation format. Using these findings, paper and
      electronic prototype versions of a guide to general practice services have been
      developed. CONCLUSIONS: In order to maximize the potential use of performance
      information by the public it is necessary to move beyond provider-led and
      professionally constructed approaches to information provision and ensure that
      the public is actively involved in the development of information sources. Such
      involvement produces a different kind of information to that currently available
      to the public. The findings of this study have important implications for policy.
      Most importantly, it seems that the traditional consumerist model underlying a
      policy of making comparative performance information available to the public to
      enable them to exercise choice between primary care providers may not be
      appropriate. An alternative model of information provision, which recognizes the
      public's commitment to their practice and is integrated with 'soft' sources of
      knowledge is more likely to engage and be of use to the public.

PMID- 16911142
TI  - What are the key attributes of primary care for patients? Building a conceptual
      'map' of patient preferences.
AB  - BACKGROUND: Responding to the preferences of patients is a key focus of current
      health policy and is especially important in primary care. Responding effectively
      to patient preferences requires a clear understanding of the way in which
      patients assess primary care services. OBJECTIVE: This study was designed to
      provide a 'map' of the content and structure of the key attributes of patient
      preferences concerning primary care. DESIGN: The development of the 'map' used
      secondary research methods. Electronic databases were searched for published
      conceptual reviews of patient preferences, which were used to develop a basic
      'map' through content analysis. A search for recently published primary empirical
      studies of patient preferences was conducted to extend and develop the 'map'. The
      'map' was tested by taking a random sample of patient assessment instruments and
      categorizing the item content. RESULTS: Seven major categories and multiple
      subcategories were described. The major categories were access, technical care,
      interpersonal care, patient-centredness, continuity, outcomes, and hotel aspects
      of care. The coverage of these attributes in a selection of patient assessment
      instruments varied widely, and the coding of a proportion of items in the patient
      assessment instruments according to the 'map' was problematic. CONCLUSIONS: The
      conceptual 'map' can be used to plan comprehensive assessment of patient
      preferences in primary care. It also raises many theoretical issues concerning
      the nature of attributes and their interrelationships. The implications for the
      measurement of patient preferences are discussed.

PMID- 16911144
TI  - Information access: an online resource for health and social care professionals
      providing information to people affected by neurological conditions.

PMID- 16911143
TI  - Who uses decision aids? Subgroup analyses from a randomized controlled
      effectiveness trial of two prostate cancer screening decision support
      interventions.
AB  - OBJECTIVE: To examine who reported using unsolicited prostate cancer screening
      decision aids distributed as part of a randomized controlled trial, whether
      reported use varied by type of aid (video or pamphlet), and what affect reported
      use had on study outcomes. METHODS: A total of 1,152 men aged 50 and older from
      four medical facilities in the United States were randomly assigned to pamphlet,
      video or usual care (control). Materials were mailed 2 weeks prior to clinic
      appointments in general internal medicine. Outcomes were assessed by phone survey
      1 week after appointments. Analyses examined the reported use of materials by
      study group, the association between patient characteristics and reported use,
      and the impact of reported use (adjusting for patient characteristics) on a 10
      item knowledge index. RESULTS: Fifty-six percent of those randomized to receive
      the video and 50% of those randomized to receive the pamphlet reported using the
      materials. Reported use of the video was higher for patients who had greater than
      a high school education (OR 1.73), were married (OR 2.20), and reported no prior
      abnormal prostate cancer screening test results (OR 3.39). Reported use of the
      pamphlet did not vary by patient characteristics. In intent-to-treat analyses
      (ignoring reported use), individuals randomized to the video and pamphlet groups
      had significantly higher knowledge scores relative to the control group (7.44,
      7.26 and 6.90 respectively). Adjusting for reported use modestly increased the
      estimated differences across treatment groups but did not substantially change
      conclusions about the relative effects of these aids on knowledge. CONCLUSIONS:
      Only half of men receiving unsolicited prostate cancer screening decision aids
      before a visit reported using the aids, and who reported using them varied by
      type of aid. Efforts to broadly implement decision aids may need to offer a
      variety of approaches, and incorporate creative strategies to enhance reaching
      all population subgroups.

PMID- 16911149
TI  - Cricothyroid muscle function and vocal fold stability in exercising horses.
AB  - OBJECTIVES: To determine (1) if the cricothyroid muscle had respiratory-related
      electromyographic (EMG) activity that increased with respiratory effort and (2)
      if bilateral cricothyroid myotomy resulted in vocal fold instability and collapse
      in exercising horses. STUDY DESIGN: Experimental. ANIMALS: Seven (3 EMG; 4
      cricothyroid myotomy) Standardbred horses. METHODS: Three horses exercised on a
      treadmill at speeds corresponding to the speed that produced maximum heart rate
      (HR(max)), 75% of maximum heart rate (HR(75%max)), and 50% of maximum heart rate
      (HR(50%max)) for 60 seconds at each speed while EMG activity of the cricothyroid
      muscle and nasopharyngeal pressures were measured. Another 4 normal horses were
      exercised on the treadmill at HR(max) and HR(75%max) for 60 seconds at each speed
      before and after bilateral cricothyroid myotomy. Upper airway pressures were
      measured and videoendoscopic examinations were performed and videotaped at each
      speed. RESULTS: Peak phasic EMBG activity of the cricothyroid muscle was
      coincident with inspiration and increased with treadmill speed. Bilateral
      cricothyroid myotomy resulted in vocal fold collapse in all horses. Mean peak
      inspiratory pressures were significantly more negative compared with control
      values at both HR(max) and HR(75%max). CONCLUSIONS: Cricothyroid muscle
      dysfunction may be implicated in vocal fold collapse and likely causes
      inspiratory airway obstruction in exercising horses. CLINICAL RELEVANCE:
      Conditions compromising cricothyroid muscle function or motor innervation could
      result in vocal fold collapse.

PMID- 16911150
TI  - Histomorphometry of fragmented medial coronoid process in dogs: a comparison of
      affected and normal coronoid processes.
AB  - OBJECTIVE: To determine if fatigue microdamage is associated with fragmented
      medial coronoid process (FMCP). STUDY DESIGN: Prospective study. ANIMALS: Thirty
      eight dogs were admitted for subtotal coronoid ostectomy as treatment for FMCP.
      Surgical specimens of medial coronoid process (MCP) were retrieved from treated
      dogs. Normal MCP were collected from 5 age- and breed-matched dogs and 2 age
      matched research beagles that were euthanatized for reasons other than elbow
      disease. METHODS: MCP specimens from affected elbows were classified into 4
      groups based on disease severity. Specimens were bulk-stained for microdamage
      using 1% basic fuchsin, embedded in polymethylmethacrylate and sectioned at 130
      microm. Specimens were evaluated using epifluorescent microscopy (425-440
      excitation, 475 nm barrier filter) for diffuse damage (D.DX), osteocyte loss, and
      porosity. Cartilage thickness was evaluated using bright field microscopy.
      Qualitative observations were also made. RESULTS: MCP specimens from affected
      elbows had increased D.Dx, increased osteocyte loss, and greater porosity than
      normal groups. Specimens classified as severe FMCP (Classes 3, 4) had the most
      fatigue microdamage. Some Class 1 specimens, defined as having no visible
      fissuring of the articular cartilage (AC), had large microcracks in trabecular
      bone. CONCLUSIONS: Accumulation of subchondral fatigue microdamage, is associated
      with MCP fragmentation. Fissuring occurs in the subchondral bone before gross
      fibrillation of articular cartilage develops. CLINICAL RELEVANCE: Accumulation of
      fatigue microdamage in the MCP is important in the pathogenesis of FMCP. The
      underlying cause of this microdamage accumulation must be identified before
      treatment plans that will prevent further osteoarthritis of the elbow joint can
      be designed.

PMID- 16911151
TI  - In vitro study of the ilial anatomic landmarks for safe implant insertion in the
      first sacral vertebra of the intact canine sacroiliac joint.
AB  - OBJECTIVE: To define landmarks on the canine ilial wing for accurate, consistent
      insertion of implants into the 1st sacral (S1) vertebral body when the sacroiliac
      joint is intact. STUDY DESIGN: Anatomic study. ANIMALS: Intact, cadaveric canine
      pelves and sacra (n=25). METHODS: Median sections (5 specimens) were drilled from
      the center of S1 in a lateral direction, exiting on the ilial wing. Landmarks on
      the ilial wing and shaft used to define this exit point were then used to locate
      this point on both wings of 20 articulated specimens, positioned and rigidly held
      so that the dorsal plane of the pelvis was aligned with a plumb line and the
      median plane of the pelvis was horizontal. A 2 mm hole was drilled from the
      marked point, parallel to the plumb line, until it exited the contralateral ilial
      wing. Distance of drill hole position from the geometric center (GC) of S1 was
      located on median and paramedian plane images derived from plane, computed
      tomographic (CT) scans. RESULTS: The entire drill hole was located within S1 in
      18 specimens. Mean deviation of the hole from GC (ratio of the distance of GC
      from the closest S1 body border) in median section was 0.40 +/- 0.29
      (craniocaudal direction) and 0.29 +/- 0.23 (dorsoventral). CONCLUSIONS: Use of
      ilial wing landmarks and drilling perpendicular to the median plane will improve
      accuracy for insertion of implants into S1 when the sacroiliac joint is intact.
      CLINICAL RELEVANCE: Ilial wing landmarks should be used to improve accuracy of
      implant insertion into S1.

PMID- 16911152
TI  - Cortical allograft and endoprosthesis for limb-sparing surgery in dogs with
      distal radial osteosarcoma: a prospective clinical comparison of two different
      limb-sparing techniques.
AB  - OBJECTIVE: To compare surgical and oncologic outcome in dogs with osteosarcoma
      (OSA) of the distal aspect of the radius treated with limb-sparing surgery, using
      either a cortical allograft or endoprosthesis, and postoperative chemotherapy;
      and to evaluate predictive factors for outcome. STUDY DESIGN: Prospective cohort
      study. ANIMALS: Dogs (n = 20) with spontaneous, non-metastatic OSA of the distal
      aspect of the radius. METHODS: Dogs were prospectively randomized for limb
      sparing surgery with either a cortical allograft (n = 10) or endoprosthesis (10)
      and full-course adjuvant chemotherapy using single or dual agent protocols of
      cisplatin, carboplatin, and/or doxorubicin. Surgical (intraoperative findings,
      postoperative infection, construct failure) and oncologic (local tumor
      recurrence, metastasis, survival) outcomes were compared. The influence of
      intraoperative and postoperative variables on surgical and oncologic outcome were
      evaluated. RESULTS: No clinically significant differences in surgical and
      oncologic outcome were detected between groups. The percentage of radius replaced
      by the implant was significantly greater in the endoprosthesis group (60.9%
      compared with 48.6%, P = .008). Median survival time (MST) for dogs with
      construct failure, regardless of implant type, was 685 days and significantly
      greater than MST of dogs without construct failure (322 days, P = .042; hazard
      ratio [HR] 16.82). Median metastasis-free interval and MST (685 days versus 289
      days; P = .034, HR 24.58) were significantly greater in dogs with postoperative
      infection. Disease-free and overall limb-salvage rates were 70% and 85%,
      respectively. Overall MST was 430 days. CONCLUSIONS: For dogs with OSA of the
      distal aspect of the radius, a cortical allograft or endoprosthesis can be used
      for limb-sparing surgery. Construct failure and postoperative infection
      significantly improve survival time regardless of implant type. CLINICAL
      RELEVANCE: An endoprosthesis is an attractive alternative to cortical allografts
      for limb-salvage of the distal aspect of the radius in dogs because surgical and
      oncologic outcomes are similar, but the endoprosthesis is an immediately
      available off-the-shelf implant which is not complicated by the bone harvesting
      and banking requirements associated with cortical allografts. Mechanisms whereby
      postoperative infection improves survival time requires further investigation
      and, if elucidated, may provide the opportunity to improve the outcome of dogs
      and humans with OSA.

PMID- 16911153
TI  - Effect of positive end-expiratory pressure on oxygen delivery during 1-lung
      ventilation for thoracoscopy in normal dogs.
AB  - OBJECTIVE: To evaluate the effect of positive end-expiratory pressure (PEEP) on
      oxygen delivery (DO(2)) with 1-lung ventilation during thoracoscopy in normal
      anesthetized dogs. STUDY DESIGN: Prospective, controlled experimental study.
      ANIMALS: Eight, adult, intact Walker Hound dogs weighing 25.6-29.2 kg. METHODS:
      Anesthetized dogs had 1-lung ventilation during an open-chest condition. A Swan
      Ganz catheter was used to measure pulmonary hemodynamic variables and to obtain
      mixed venous blood samples for blood gas analysis. A dorsal pedal catheter was
      used for measurement of systemic arterial pressure and to obtain arterial blood
      samples for blood gas analysis. Oxygen delivery was calculated and used to assess
      the effect of 0, 2.5, and 5 cm H(2)O PEEP during 1-lung ventilation on
      cardiopulmonary function. Each dog was its own control at 0 cm H(2)O PEEP. A
      randomized block ANOVA for repeated measures was used to evaluate the effect of
      the treatment on hemodynamic and pulmonary variables. RESULTS: Use of 5 cm H(2)O
      PEEP induced a significant augmentation in the arterial partial pressure of
      oxygen (PaO(2)). Shunt fraction (Q(s)/Q(t)), physiologic dead space (V(D)/V(T)),
      and the alveolar-arterial oxygen difference (P(A-a)O(2)) decreased significantly
      after 5 cm H(2)O PEEP, compared with 1-lung ventilation without PEEP. Use of 2.5
      cm H(2)O PEEP had no significant effect on cardiopulmonary variables. Use of PEEP
      had no significant effect on arterial oxygen saturation (SaO(2)), DO(2), and
      hemodynamic variables in normal dogs. CONCLUSIONS: PEEP had no effect on DO(2) in
      normal dogs undergoing open-chest 1-lung ventilation because it had no adverse
      effect on hemodynamic variables. CLINICAL RELEVANCE: PEEP in normal dogs during
      open-chest 1-lung ventilation for thoracoscopy is not detrimental to cardiac
      output and can be recommended in clinical patients.

PMID- 16911154
TI  - Evaluation of the effect of two dose rates of cyclosporine on the severity of
      perianal fistulae lesions and associated clinical signs in dogs.
AB  - OBJECTIVE: To investigate the effect of cyclosporine (2 or 5 mg/kg every 24
      hours) on perianal fistulae (PAF) lesions. STUDY DESIGN: Blinded randomized,
      prospective trial. ANIMALS: Dogs (n = 20) with perianal fistulae. METHODS: Dogs
      were randomly assigned to administration of either 2 mg/kg (n = 10) or 5 mg/kg
      (n=10) of cyclosporine orally every 24 hours for 8 weeks. Lesion surface area was
      measured, lesion severity was graded using a visual analog scale, and the
      presence and severity of clinical signs recorded every 2 weeks. RESULTS: Lesion
      variables were significantly reduced in both groups after 8 weeks and owners also
      reported a reduction in clinical sign severity. The 5 mg/kg dose rate
      significantly accelerated lesion resolution compared with 2 mg/kg. In the 2 mg/kg
      group, 20% of dogs had complete resolution of clinical signs and 10% had
      resolution of lesions. In the 5 mg/kg group, 40% of dogs had complete resolution
      of clinical signs and 60% had resolution of lesions. CONCLUSIONS: A dose rate of
      5 mg/kg every 24 hours was more effective at reducing the surface area and
      severity of PAF lesions than 2 mg/kg every 24 hours but less effective at
      resolving PAF lesions than previous studies using dose rates > or =5 mg/kg every
      12 hours. CLINICAL RELEVANCE: Cyclosporine at 5 mg/kg every 24 hours may be
      useful for the palliation of PAF lesions.

PMID- 16911155
TI  - Radiographic evaluation of the Zurich cementless total hip acetabular component.
AB  - OBJECTIVE: To radiographically evaluate the Zurich cementless total hip (ZCTH)
      cup and correlate lucency with clinical signs of implant instability, time since
      surgery, and implant generation, using zonal analysis. STUDY DESIGN:
      Retrospective study. ANIMALS: Client-owned dogs (n = 53). METHODS: Radiographs of
      dogs that had ZCTH arthroplasty (>1 year) were evaluated using zonal analysis,
      for lucency surrounding the cup-bone interface (number of zones, length, area).
      Dogs were examined for clinical signs of implant instability (lameness, hip
      pain). Lucency was correlated with lameness, time after surgery, and implant
      generation. RESULTS: Radiographs of 68 implants (18 generation I, 50 generation
      II) were evaluated. Eight dogs were lame (11.8%). Dogs with lameness were more
      likely to have lucency in > or =2 zones of analysis (per view), have >2 times the
      average curvilinear length of lucency, and have >4 times the average area of
      lucency surrounding the implant compared with non-lame dogs. A weak relationship
      was observed between time after surgery and implant generation; however, there
      was no relationship between time after surgery and lucency. CONCLUSIONS: Dogs
      with lameness after ZCTH arthroplasty were more likely to have lucency at the cup
      bone interface. Lucency was better evaluated by radiographic projection than
      zonal analysis. Temporal progression of lucency was weakly correlated with
      implant generation. CLINICAL RELEVANCE: Dogs with lucency in > or =2 zones of
      analysis should be evaluated more frequently for clinical signs of implant
      loosening. Further investigation of serial radiographs after ZCTH arthroplasty is
      warranted.

PMID- 16911156
TI  - Complications associated with corrective surgery for patellar luxation in 109
      dogs.
AB  - OBJECTIVE: To review surgical techniques and postoperative complications
      associated with correction of patellar luxation in dogs. STUDY DESIGN:
      Retrospective study. ANIMALS: Dogs (n = 109) with patellar luxation (n = 131).
      METHODS: Medical records of dogs that had corrective surgery for patellar
      luxation were reviewed. Signalment, history, grade and direction of patellar
      luxation, operative technique and clinical outcomes were retrieved. RESULTS:
      Overall frequency of postoperative complications was 18%. Frequency of major
      (requiring revision surgery) complications was 13%. Frequency of patellar
      reluxation was 8%. Frequency of overall, major, and patellar reluxation
      complications was higher for dogs weighing > or =20 kg compared with those <20
      kg. Frequency of overall and major complications was higher for dogs with higher
      grades of patellar luxation. Femoral trochlear sulcoplasty resulted in lower
      frequency of patellar reluxation. Tibial tuberosity transposition (TTT) resulted
      in lower frequency of major complications and patellar reluxation.
      Retinacular/capsular release resulted in higher frequency of major complications.
      Patient age, gender, medial versus lateral patellar luxation, left versus right
      hindlimb, capsular/retinacular imbrication, use of anti-rotational sutures, and
      whether stifle surgery had been performed previously did not significantly
      influence frequency of complications. CONCLUSION: TTT and femoral trochlear
      sulcoplasty minimize the risk of postoperative patellar reluxation and major
      complications. CLINICAL RELEVANCE: Information derived from this study can be
      used to estimate the likelihood of postoperative complications for canine
      patients undergoing corrective surgery for patellar luxation.

PMID- 16911157
TI  - Mechanical comparison of two knots and two crimp systems for securing nylon line
      used for extra-articular stabilization of the canine stifle.
AB  - OBJECTIVE: To compare mechanical properties of knotted and crimped nylon loops.
      STUDY DESIGN: In vitro mechanical evaluation. SAMPLE POPULATION: Loops of 27 kg
      test nylon leader. Single strand-clamped square knot compared with 2 crimp
      systems. Two strand--self-locking knot compared with 2 crimped loops. METHODS:
      (a) Single pull to failure (n = 10) at 500 mm/min. Initial loop tension (N), peak
      load (N), peak elongation (mm), stiffness of the linear portion of the curve
      (N/mm), and failure mode were recorded. (b) Incremental cyclic loading to failure
      (n = 5)--each loop was cycled 5 times to 100 N at a loading rate of 200 mm/min.
      Cycling was repeated, with the load increased by 50 N after each set. Elongation
      (mm), tension remaining (N), and after permanent deformation was present,
      elongation at 10 N (mm) were measured. RESULTS: Initial tension and stiffness
      were greater for crimped loops when compared with knotted loops. There were no
      differences between crimped loops. The self-locking knot elongated more, and was
      less stiff, when compared with 2 crimped loops. With incremental loading, knotted
      loops elongated more than crimped loops. The tension remaining in the loop fell
      below 10 N more quickly for knotted loops compared with crimped loops.
      CONCLUSION: Crimped loops are stiffer, and resist both static and cyclic load
      more effectively before becoming permanently elongated, when compared with
      knotted loops. CLINICAL RELEVANCE: Stifle stability will be maintained more
      effectively by crimped nylon loops when compared with knotted loops.

PMID- 16911158
TI  - Fatigue analysis of plates used for fracture stabilization in small dogs and
      cats.
AB  - OBJECTIVE: To evaluate the fatigue life of stacked and single, veterinary
      cuttable plates (VCP) and small, limited contact, dynamic compression plates (LC
      DCP). STUDY DESIGN: In vitro biomechanical study. METHODS: Fracture models
      (constructs; n = 8) were assembled for each of 6 groups all with 8-hole plates:
      2.0 mm LC-DCP; 2.4 mm LC-DCP; single 1.5/2.0 mm VCP; stacked 1.5/2.0 mm VCP;
      single 2.0/2.7 mm VCP; and stacked 2.0/2.7 mm VCP. Plate(s) were secured to 2
      polyvinylchloride pipe lengths, mounted in a testing system with a custom jig,
      and subjected to axial loading (10-100 N) for 1,000,000 cycles at 10 Hz or until
      failure. Differences in number of cycles to failure among groups were compared.
      Failure mode was determined. RESULTS: All LC-DCP and single VCP constructs failed
      before 1,000,000 cycles. Stacked 2.0/2.7 mm VCP constructs withstood 1,000,000
      cycles without failure. ANOVA and Fisher's least significant difference tests
      demonstrated significantly more cycles to failure for the stacked 1.5/2.0 mm VCP
      and stacked 2.0/2.7 mm VCP compared with the single 1.5/2.0 mm VCP, single
      2.0/2.7 mm VCP, 2.0 mm LC-DCP, or 2.4 mm LC-DCP. Constructs that failed did so
      through a screw hole adjacent to the gap. CONCLUSION: Stacked VCP constructs have
      greater fatigue lives than comparably sized LC-DCP or single VCP constructs.
      Plates with 2.4 mm screws were not significantly different from the comparable
      construct with 2.0 mm screws. CLINICAL RELEVANCE: Although these data reveal that
      stacked VCP create a superior construct with respect to cyclic fatigue, surgeons
      must decide whether this is a clinical advantage on a case-by-case basis.

PMID- 16911159
TI  - The prevalence of laryngeal disease in a large population of competition draft
      horses.
AB  - OBJECTIVES: (1) To determine the effect of age, height, weight, breed, sex, and
      specific use on the prevalence of idiopathic left laryngeal hemiplegia (ILH) in a
      population of draft performance horses; (2) to determine the association between
      tracheal mucus and laryngeal dysfunction, and the prevalence of exercise-induced
      pulmonary hemorrhage (EIPH) in a population of draft performance horses. STUDY
      DESIGN: Cross-sectional. ANIMALS: Draft horses competing at the 2005 Michigan
      Great Lakes Draft Horse Show. METHODS: Endoscopic examinations were performed on
      horses competing at the 2005 Michigan Great Lakes Draft Horse Show. Signalment,
      height, and weight were obtained from the owners and trainers. RESULTS: Belgian,
      Percheron, and Clydesdale horses (n=183) were studied. Prevalence of ILH was 35%.
      Horse height was significantly associated with the risk of ILH in Belgian and
      Percheron horses but not Clydesdales. There was a significantly different
      prevalence of ILH among the breeds such that 42% Belgians, 31% Percherons, and
      17% Clydesdales were affected. Laryngeal disease was a risk factor for increased
      tracheal mucus. None of the horses had acute evidence of EIPH. CONCLUSIONS: The
      prevalence of ILH in draft horses has increased or is higher in competition
      horses compared with previously studied groups. Tracheal and/or pulmonary
      inflammation may be more common in draft horses with ILH based on our findings
      that horses with ILH have more tracheal mucus than horses with normal laryngeal
      function. CLINICAL RELEVANCE: Selection pressure for large, taller, longer-necked
      horses may be responsible for a seemingly increased incidence of ILH in
      competitive draft horses.

PMID- 16911160
TI  - Vocal fold collapse after laryngeal tie-forward correction of dorsal displacement
      of the soft palate in a horse.

PMID- 16911161
TI  - Treating acute mental illness in rural general hospitals: necessity or choice?
AB  - OBJECTIVE: To identify reasons why rural general practitioners (GPs) treat a
      large proportion of patients with a primary psychiatric diagnosis in general beds
      of their local hospitals, and the barriers encountered when providing this
      treatment. DESIGN: A postal questionnaire was developed and distributed to a
      sample of rural GPs, asking about the treatment of patients with an acute mental
      illness in their local hospital. RESULTS: The majority of GPs agreed that they
      treat the acutely mentally ill in general beds of their local hospital due to
      lack of availability of, and inability to gain access to, mental health beds in
      the larger centres; and also to enable ongoing family involvement and continuity
      of care. Distance factors were identified as least significant. Barriers to
      providing care to this group of patients included a perceived lack of support by
      consultant psychiatrists, confidentiality issues, lack of community mental health
      workers to provide assistance, aggression levels of patients, inappropriate local
      hospital setting, and lack of confidence of GPs and general hospital nursing
      staff. CONCLUSION: Addressing these barriers is necessary if rural Australians
      are to receive a quality of care that is equal to that received by those located
      in metropolitan Australia. Continuing research in this area is crucial.

PMID- 16911162
TI  - Community participation in organising rural general practice: is it sustainable?
AB  - OBJECTIVE: We analysed community participation in organising rural general
      medical practice in order to suggest ways to extend and sustain it. DESIGN: A
      multisite, embedded case-study design collecting data through semistructured
      interviews, non-participation observation and a document analysis. SETTING: One
      remote and two rural communities in Australia. PARTICIPANTS: Community members,
      GPs, health professionals, government officers and rural medical workforce
      consultants. RESULTS: High levels of community participation in recruiting and
      retaining GPs, organising the business model, and contributing to practice
      infrastructure were evident. Community participation in designing health care was
      uncommon. Participation was primarily to ensure viable general practice services
      necessary to strengthen the social and economic fabric of the community. There
      were factors about the decision-making and partnership processes in each of the
      communities that threatened the viability of community participation.
      CONCLUSIONS: We recommend that a concept of community development and explicit
      facilitation of the processes involved is necessary to strengthen participation,
      create effective partnerships and ensure inclusive decision-making.

PMID- 16911163
TI  - Co-morbid drug and alcohol and mental health issues in a rural New South Wales
      Area Health Service.
AB  - OBJECTIVE: In 2003 the New South Wales (NSW) Centre for Rural and Remote Mental
      Health (CRRMH) conducted an analysis of co-morbid drug and alcohol (D&A) and
      mental health issues for service providers and consumers in a rural NSW Area
      Health Service. This paper will discuss concerns raised by rural service
      providers and consumers regarding the care of people with co-morbid D&A and
      mental health disorders. DESIGN: Current literature on co-morbidity was reviewed,
      and local area clinical data were examined to estimate the prevalence of D&A
      disorders within the mental health service. Focus groups were held with service
      providers and consumer support groups regarding strengths and gaps in service
      provision. SETTING: A rural Area Health Service in NSW. PARTICIPANTS: Rural
      health and welfare service providers, consumers with co-morbid D&A and mental
      health disorders. RESULTS: Data for the rural area showed that 43% of inpatient
      and 20% of ambulatory mental health admissions had problem drinking or drug
      taking. Information gathered from the focus groups indicated a reasonable level
      of awareness of co-morbidity, and change underway to better meet client needs;
      however, the results indicated a lack of formalised care coordination, unclear
      treatment pathways, and a lack of specialist care and resources. DISCUSSION:
      Significant gaps in the provision of appropriate care for people with co-morbid
      D&A and mental health disorders were identified. Allocation of service
      responsibly for these clients was unclear. It is recommended that D&A, mental
      health and primary care services collaborate to address the needs of clients so
      that a coordinated and systematic approach to co-morbid care can be provided.

PMID- 16911165
TI  - An outbreak of acute post-streptococcal glomerulonephritis in remote Far North
      Queensland.
AB  - BACKGROUND: To observe and record an outbreak of acute post-streptococcal
      glomerulonephritis (APSGN) in the Lockhart River community in 2005 and the steps
      taken by health workers to contain the epidemic. METHODS: A descriptive study of
      cases of APSGN and children aged from 2 to 12 years involved in the screening
      program. SETTING: A remote indigenous community in Far North Queensland.
      PARTICIPANTS: All children aged from 2 to 12 years in the Lockhart River
      community. RESULTS: Eighty-seven children were screened. And 46% were found to
      have infected scabies. CONCLUSIONS: There were 11 confirmed cases of APSGN over
      four months from February to May. Infected scabies was the main preceding finding
      in these children.

PMID- 16911164
TI  - Statistical methods for analysis of repeated measures on maternal morbidity.
AB  - OBJECTIVES: This paper applies statistical methods to identify factors associated
      with pregnancy-related complications in rural Bangladesh. The results are
      examined in order to identify the factors that can help formulate policy for
      reducing pregnancy-related morbidity. METHODS: Two statistical methods are used
      in this study to analyse the repeated-measures data on pregnancy-related
      complications in rural Bangladesh. One method is based on the application of
      linear logistic regression at each follow up, and the results are compared to
      identify the potential risk factors. Then the generalised estimating equation
      (GEE) approach is used, and the results based on each follow up are compared with
      those obtained from the application of the GEE approach. The maternal morbidity
      data collected by the Bangladesh Institute of Research for Promotion of Essential
      and Reproductive Health and Technologies are used in this paper. RESULTS:
      Economic status, visit for antenatal care, and histories of sexually transmitted
      disease, hypertension, heart disease and breathing problem are positively
      associated with the complications during pregnancy, while wanted pregnancy,
      household type, primary and secondary schooling, and five or more pregnancies are
      associated negatively with the response variable. Involvement with gainful
      employment shows a negative association by the first technique. The GEE approach
      failed to identify some important factors such as history of anaemia, previous
      pregnancy and gainful employment. However, duration of pregnancy appears to have
      an association with pregnancy complications, which was not found from the
      conditional model based on each follow up. CONCLUSION: It appears that unwanted
      pregnancies need to be reduced through a well-organised and targeted family
      planning campaign for potential mothers of all ages in rural Bangladesh.
      Nutritional anaemia may cause various complications, and suggestions are given
      for reducing anaemia among pregnant women. In the rural areas of Bangladesh,
      first births usually occur at teenage. The first-birth pregnancy among teenagers
      can be a source of severe complications. There can be special programs to address
      the need for delay in the first pregnancy of those who marry at an early age.

PMID- 16911166
TI  - Hearing loss in recreational shooters in Central Queensland: a pilot study.

PMID- 16911167
TI  - Focus on healthy behaviours: not just on weight.

PMID- 16911168
TI  - Measuring health promotion activities of rural community pharmacy.

PMID- 16911171
TI  - Reflections on the ethics involved in international research.

PMID- 16911172
TI  - A nurse-led rheumatology clinic's impact on empowering patients with rheumatoid
      arthritis: A qualitative study.
AB  - The aim of this study was to describe a nurse-led rheumatology clinic's impact on
      empowering patients with rheumatoid arthritis (RA). Rheumatoid arthritis is a
      chronic, inflammatory disease that attacks many joints, causing considerable
      functional restrictions for patients. Consequently, these patients are dependent
      on a wide variety of health-care services. A descriptive, qualitative design
      inspired by phenomenography was chosen. The conceptions were collected through
      interviews with 16 strategically selected patients with RA. Three descriptive
      categories comprising eight conceptions emerged: teaching (gaining insight and
      receiving information), regular review (receiving security, realizing regularity,
      and achieving accessibility), and attention (getting a holistic assessment,
      receiving coordinated care, and getting sufficient time). A nurse-led
      rheumatology clinic can be a source for empowering patients with RA to adopt new
      stances to alternative actions and achieve a higher level of faith in their own
      abilities.

PMID- 16911173
TI  - Efficacy of comprehensive group rehabilitation for women with early breast cancer
      in South Korea.
AB  - The purpose of this study was to evaluate the effects of a comprehensive group
      rehabilitation program on the range of motion of the shoulder joint, psychosocial
      adjustment, and the quality of life for early breast cancer patients. Fifty-five
      women with early breast cancer were assigned to an intervention group or a
      control group. Intervention was provided three times per week for 10 weeks. The
      results showed an increased range of motion of the shoulder joint, and
      psychosocial adjustment and quality of life were shown to be significantly higher
      in the intervention group than in the control group. The rehabilitation program
      comprised psychology-based education, exercise, and peer support group activity
      to promote recovery of the affected shoulder joint range of motion, alleviate
      physical symptoms, and improve psychosocial adjustment and quality of life for
      early breast cancer patients in South Korea.

PMID- 16911174
TI  - Investigation of the relationships among workplace stressors, ways of coping, and
      the mental health of Chinese head nurses.
AB  - Limited information exists about which workplace events are stressful for nurses
      in charge of a hospital patient-care unit (head nurse) in China and how these
      nurses cope with these events. Therefore, the purposes of this descriptive study
      were to examine workplace stressors, ways of coping, and the levels of mental
      health of Chinese head nurses, as well as to identify the relationships among the
      workplace stressors, ways of coping, and mental health of Chinese head nurses. To
      address these purposes, four self-report questionnaires were administered to a
      convenience sample of 92 head nurses from two teaching hospitals located in one
      city in central China. The findings suggested that workload, death/dying, and
      conflict with physicians were the most predominant sources of workplace stress,
      while the most frequent coping strategies used were positive reappraisal, planful
      problem solving, and self-control. The mental health scores were found to be
      lower than prior research has suggested for some nurses in Asia. A number of
      significant correlations were found among demographic characteristics, workplace
      stressors, ways of coping, and mental health.

PMID- 16911175
TI  - The meanings of pain: A qualitative study of the perspectives of children living
      with pain in north-eastern Thailand.
AB  - This qualitative paper explores the perception of pain among north-eastern Thai
      children experiencing illness, aged from 4-18 years. Data was obtained from 17
      children living in the community and 32 children admitted to two major hospitals
      in Isan, totaling 49 children. The qualitative data collection techniques used
      were observation, drawing, role-playing, story-telling, and "day conferences"
      (relaxed and informal group discussions). The study was conducted over 1 year and
      the data were analyzed using Fielding's method of content analysis. The research
      found that children described their experience of pain as "disheartening",
      "suffering", and "torturing" and that the expression of pain in Isan families is
      characterized by avoidance and endurance. The findings suggest a role for a model
      of pain management in children specific to the sociocultural context of Isan,
      which focuses on family-centered care and acknowledges cultural diversity.

PMID- 16911176
TI  - Preventing tobacco and drug use among Thai high school students through life
      skills training.
AB  - Tobacco and drug use remain major public health concerns. The aim of this study
      was to evaluate the effectiveness of a school health intervention program using
      life skills training (LST) to reduce tobacco and drug use among Thai high school
      students. A randomized pretest and post-test comparative design was used to
      evaluate the effectiveness of the LST program. A total of 170 Thai students in
      grades 7-12 were randomly selected. The students in the control group received
      the tobacco and drug education curriculum normally provided; the intervention
      group received a LST program that provided information and skills specifically
      related to drug and tobacco use. Students in the school health intervention
      program had statistically significant positive effects regarding knowledge level,
      attitudes, and the development of refusal, decision-making, and problem-solving
      skills. The results showed that a LST program was effective for preventing
      tobacco and drug use in Thai high school students.

PMID- 16911177
TI  - Grassroots efforts of Japanese women to promote services for abused women.
AB  - The purpose of this study was to identify and describe the personal experiences
      of six Japanese female volunteers who formed a support group to provide services
      for abused women. The interpretation of the women's stories also increased
      understanding about the process of forming and developing a grassroots
      organization to take needed action. The interpretive phenomenological approach
      guided the study. The findings illustrate that a group of community volunteers
      can identify and effectively address a significant social issue on their own
      initiative.

PMID- 16911178
TI  - Facilitating help-seeking through student interactions in a WebCT online graduate
      study program.
AB  - This article discusses a qualitative research project that revealed how online
      health-care practitioners in a graduate studies program believe their primary
      source of help is other students in their class. The project was framed from a
      constructivist theoretical perspective and an action research approach. The
      participants were clinicians, such as advanced nurse practitioners, who graduated
      from a Master of Nursing or Master of Health Studies program offered exclusively
      through a WebCT online environment. The data sources included a program
      satisfaction survey, focus groups, and 10 individual audiotape-recorded and
      transcribed interviews. The data were collected over a 2 year period, analyzed
      for themes by two researchers, and confirmed with the participants through
      ongoing member-checking. The following four strategies to facilitate help-seeking
      interactions among online graduate study learners are presented: award marks for
      participation, encourage thoughtful, well-crafted introductions, create a coffee
      lounge, small group forums and private email within the course environment, and
      identify non-contributing students.

PMID- 16911179
TI  - Characteristics of nausea and vomiting in pregnant Japanese women.
AB  - Nausea and vomiting in pregnancy (NVP) is a common condition in early pregnancy.
      The purpose of this study was to clarify the characteristics of Japanese women's
      NVP and to determine the relationship between NVP and quality of life. The NVP
      was measured using the Rhodes' Index and quality of life was measured by the SF
      36. Nausea and retching at 4-7 and 12-15 weeks was significantly more severe than
      at 16-19 weeks, whereas there was no difference in vomiting. A decrease in
      physical well-being was correlated with the severity of nausea and retching at 8
      11 and 12-15 weeks, but not with that of vomiting at any gestational period.
      Although the symptom of vomiting tended to be noticed more frequently, nausea and
      retching was more important in the care and treatment of NVP in Japanese women
      than vomiting, suggesting that professionals should carefully measure NVP
      symptoms using reliable instruments.

PMID- 16911180
TI  - Continuity of care and quality care outcomes for people experiencing chronic
      conditions: A literature review.
AB  - Continuity of patient care is frequently linked to quality care outcomes. The
      purpose of this paper is to examine the clinical trial literature in order to
      determine the extent to which informational, management, and relational
      continuity of care are associated with quality care indicators. A MEDLINE search
      of the literature via PubMed was conducted for clinical trials that were carried
      out from 1 January 1996-1 June 2005. Analyses of 32 unduplicated citations
      revealed a focus on one or more aspects of continuity and its association with
      quality care outcomes. Management continuity interventions were identified most
      often, followed by informational and relational continuity interventions. The
      outcomes were primarily patient-focused with a wide range of functional status,
      quality of life, and patient satisfaction indicators. This analysis provides
      implications for research that could contribute to an understanding of the types
      of continuity of patient care and their relationships to quality care.

PMID- 16911181
TI  - Dialysis update in Japan.

PMID- 16911182
TI  - Plasma lipoprotein abnormalities in hemodialysis patients--clinical implications
      and therapeutic guidelines.
AB  - Patients with advanced stages of chronic kidney disease (CKD) have an increased
      risk of death from cardiovascular disease (CVD). Dyslipidemias are associated
      with atherosclerotic vascular changes and the risk of occurrence of acute
      myocardial infarction in hemodialysis patients. However, management of
      dyslipidemia in hemodialysis patients does not appear to be actively carried out
      in routine practice. Presumably, there are three reasons for this reluctance to
      lipid-lowering in hemodialysis patients. First, there are epidemiological data
      showing the inverse relationship between cholesterol and mortality rate; a high
      cholesterol predicts a better survival. Second, lipids are not usually measured
      using standard fasting serum, but a non-fasting specimen. Third, although
      hypertriglyceridemia is the most common abnormality, fibrates are contraindicated
      in patients with renal failure because of a high risk of rhabdomyolysis. These
      issues are discussed in the current review article. Based on published work,
      lipid lowering would not increase the death rate if carried out without worsening
      malnutrition. The National Kidney Foundation K/DOQI Clinical Practice Guidelines
      recommend a reduction in fasting LDL-C below 100 mg/dL for the prevention of CVD
      in dialysis patients. Practically, however, the use of non-HDL-C measured by
      casual blood samples might be sufficient for the risk assessment in many
      hemodialysis patients. Statins are a good choice for lipid-lowering in dialysis
      patients. Furthermore, lipoprotein profile might be improved by an inventive use
      of dialyzer membranes, dialysate solutions, and other dialysis-related
      medications. For severe hypercholesterolemia, LDL-apheresis is another choice for
      consideration. Further studies are needed to clearly prove the benefit of lipid
      reduction in hemodialysis patients and those with CKD at earlier stages.

PMID- 16911183
TI  - Current clinical aspects of dialysis-related amyloidosis in chronic dialysis
      patients.
AB  - The current understanding of dialysis-related amyloidosis has evolved over the
      past two decades. In the early 1980s, several researchers found amyloid deposits
      in the synovia of carpal tunnel syndrome (CTS), which have been recognized as a
      complication of chronic hemodialysis. The enigma was resolved in 1985, when beta2
      microglobulin (beta2-m) with a molecular weight of 12,000 Da was identified as
      the major constitutional protein of this amyloid. Amyloid fibrils of this type
      that contain the sub-unit protein of human leukocyte antigens (HLA), beta2-m,
      deposit predominantly in osteoarticular tissues, inducing musculoskeletal
      symptoms such as CTS, polyarthralgia, bone cyst showing radiolucency at X-ray
      examination and destructive spondyloarthropathy. In addition, extra articular
      symptoms such as ischemic colitis, megaloglossia, and heart failure, that is,
      systemic involvement occasionally occur. We confirmed that the prevalence of CTS
      increases with duration of dialysis. Most patients with CTS associated with beta2
      m amyloid deposits have undergone hemodialysis for 10 years or more. Up to 50% of
      patients had developed this complication after 20 years and the percentage was
      even higher after 25 years. General categories of therapeutic approaches for
      amyloidosis include prevention of onset or progression, symptomatic therapy
      (conservative treatment, orthopedic procedures, and physiotherapy), and renal
      transplantation. It is critical to elucidate the detail mechanisms of the amyloid
      fibril formation, and establish its radical treatment. It is also important to
      develop novel therapies such as cell implantation to compensate for normal kidney
      functions of uremic toxin protein metabolism.

PMID- 16911184
TI  - Independent risk factors for progression of coronary atherosclerosis in
      hemodialysis patients.
AB  - Not uncommonly, hemodialysis patients with normal results in myocardial perfusion
      tests can still have a cardiac event within 2 years of evaluation. We examined
      possible risk factors for progression of coronary atherosclerosis in hemodialysis
      patients. We prospectively evaluated ability of myocardial perfusion imaging
      carried out under pharmacologic stress to predict 2-year outcomes in 77
      hemodialysis patients, specifically thallium-201 single-photon emission computed
      tomography (SPECT) using high-dose adenosine triphosphate as the stressor. The
      primary end-point was a cardiac event (cardiac death, non-fatal acute coronary
      syndrome, or hospitalization for acute ischemic heart failure). Factors
      independently influencing duration until a cardiac event in hemodialysis patients
      were identified using stepwise multiple regression analysis. Myocardial perfusion
      defects were shown in 36 patients. Patients with a perfusion defect were more
      likely to have cardiac events than those with normal perfusion (78% vs. 15%, P <
      0.001). Time until occurrence of a cardiac event in hemodialysis patients showed
      a significant, independent association with known coronary artery disease
      [regression coefficient (RC) = -3.391, P = 0.046], elevated C-reactive protein
      (RC = -5.813, P = 0.005), and a reversible myocardial perfusion defect (RC = 
      7.386, P < 0.001). An analysis based on the 'best cut-off' of CRP as identified
      on the basis of the ROC curve augmented the positive and negative predict value
      of CRP for the prediction of coronary events to 65 and 74%, respectively.
      Myocardial perfusion SPECT and measuring the plasma concentration of CRP might be
      useful for the prediction of hemodialysis patients with progression of coronary
      atherosclerosis.

PMID- 16911185
TI  - Diagnosis and treatment of depression in dialysis patients.
AB  - A high prevalence of depressive disorder, between 33% and 50%, has been reported
      in dialysis patients, although it is difficult to distinguish the physical
      symptoms like general fatigue, insomnia, and loss of appetite which are common
      among dialysis patients, from the psychiatric symptoms seen in depressive
      patients. Furthermore, co-occurrence of depression has been shown to be one of
      the risk factors of poor prognosis in dialysis patients, partly because depressed
      patients are less likely to adhere to their medication regimen and modify their
      lifestyle appropriately. The efficacy of psychiatric interventions, including
      pharmacotherapy and psychotherapy, has been examined for dialysis patients with
      co-occurrence of depression. Randomized controlled trials of psychiatric
      interventions for depression in dialysis patients are needed to investigate the
      impact of such interventions on depression, quality of life, and mortality.

PMID- 16911186
TI  - New therapeutic option for autosomal dominant polycystic kidney disease patients
      with enlarged kidney and liver.
AB  - The kidneys of patients with autosomal dominant polycystic kidney disease (ADPKD)
      usually continue to increase in size even after patients begin dialysis, and mass
      effects can lead to severe complications. Thus far, renal manifestations of this
      disorder have been discussed only from the viewpoint of cyst formation or
      cytogenesis, not from that of vascular abnormality. Because kidneys in ADPKD
      patients are usually supplied by well-developed arteries, we attempted renal
      contraction therapy in ADPKD patients with renal transcatheter arterial
      embolization (TAE) using intravascular coils. Mainly peripheral branches of renal
      arteries encircling the cysts were embolized. Our treatment has been confirmed to
      be effective in 266 patients until 2005. Renal size continued to decrease to 53%
      of the pre-TAE after 1 year. Almost all patients have had improved quality of
      life and nutritional status. We next tried TAE in 76 intractable patients with
      symptomatic polycystic liver. We tried to embolize only the hepatic segments
      replaced by cystic lesions in which the hepatic arteries were well-developed but
      the intrahepatic portal vein was obstructed. Sixty-four patients have had a good
      clinical course with this method. Based on our observation of ADPKD through
      treatment with TAE, we speculate that cyst growth in both the kidney and the
      liver progresses via the mechanism of 'arteriogenesis' of large vessels as well
      as 'angiogenesis' of small vessels.

PMID- 16911187
TI  - Present status and perspective of the development of a bioartificial kidney for
      chronic renal failure patients.
AB  - A bioartificial tubule device was applied for the treatment of 10 acute renal
      failure and multiple organ failure patients by Humes et al. A bioartificial
      kidney for chronic renal failure patients, however, has never been applied. In
      order to develop a bioartificial kidney for preventing and treating long-term
      complications of maintenance dialysis patients, we have to overcome difficulties
      such as antithrombogenic issue of hemofilters and development of long functioning
      tubule devices in the context of economical and easy treatment. Continuous
      hemofilters should modify with an antithrombogenic material on the inner surfaces
      of membranes to get more hemocompatible characteristics. We are developing an
      antithrombogenic continuous hemofilter coating with methacryloyloxyethyl
      phosphorylcholine polymer which will mimic phospholipid layers of human cell
      membrane on the inner surface of a hemofilter. The transportability of H2O, Na+,
      and glucose of bioartificial tubule devices using polysulfone hollow fiber
      modules and porcine proximal tubular epithelial cells LLC-PK1 were evaluated
      using two kinds of circuits of different medium inside and outside of the cell
      attached hollow fiber membrane. Transport of H2O, Na+, and glucose were
      significantly increased when 2.5 g/dL of albumin was added, and plateaued on the
      eight day and then decreased thereafter until the 13th day. Transfection of a
      specific gene into human tubular epithelial cells might be required to keep
      contact inhibition in order to maintain a confluent monolayer for longer
      duration.

PMID- 16911188
TI  - Review: Clinical usefulness of ultrapure dialysate--recent evidence and
      perspectives.
AB  - It has generally been accepted that biological contamination of dialysate
      deteriorates the biocompatibility of dialysis therapy and accelerates dialysis
      related complications such as dialysis-related amyloidosis (DRA) and malnutrition
      inflammation-atherosclerosis (MIA) syndrome. During the past decade several
      studies have clarified that very slight amounts of contamination can lead to
      inflammatory response, and we could not confirm biological dialysate quality only
      by measuring endotoxin levels despite of measuring viable cell counts or
      biofilms. To achieve this, the European Renal Association/European Dialysis
      Transplantation Association and the American National Standardization
      Institute/Association for the Advancement of Medical Instrumentation published
      new standards for dialysate, in which very strict control levels were recommended
      with regard to viable bacterial cell counts. In 2004 JSDT raised the required
      standard of the levels of endotoxin, and began to develop a standard for
      bacterial cell counts. In Japan, many chronic kidney disease patients are treated
      with centralized dialysate supply systems which have weak spots in disinfecting
      the system. This causes some difficulties in making a standard for viable
      bacterial cell counts. In the present paper, we summarize evidences of clinical
      usefulness of ultrapure dialysate and perspectives of the standard for dialysate
      in Japan.

PMID- 16911189
TI  - Therapeutic strategies for secondary hyperparathyroidism in dialysis patients.
AB  - Secondary hyperparathyroidism (SHPT) leads not only to bone disorders, but also
      to cardiovascular complications in long-term dialysis patients. Conventional
      treatment with calcium (Ca) supplement, phosphate (P) binders and active vitamin
      D analogs lead in part to amelioration of SHPT, but are simultaneously associated
      with unacceptable side-effects, including hypercalcemia, hyperphosphatemia, and
      increased Ca x P products, which are the risk factors for cardiovascular disease
      in dialysis patients. Conventional treatment has been unable to facilitate the
      attainment of optimal management of SHPT proposed in the K/DOQI guidelines.
      Cinacalcet HCl (cinacalcet), a novel calcimimetic compound, restores the
      sensitivity of the Ca-sensing receptor in parathyroid cells, and decreases serum
      parathyroid hormone (PTH) without introducing hypercalcemia or hyperphosphatemia.
      Cinacalcet treatment enables a significant number of patients to achieve the
      K/DOQI guideline. Based on experimental data, calcimimetics could ameliorate
      cardiovascular calcification and remodeling in uremic rats with SHPT. Clinical
      trials have shown that cinacalcet significantly reduced the risks of
      parathyroidectomy, fracture and cardiovascular hospitalization among long-term
      dialysis patients with SHPT. Parathyroid intervention therapy (parathyroidectomy
      and percutaneous direct injection) is also a useful alternative. In the present
      article, we review novel therapeutic strategies for SHPT.

PMID- 16911190
TI  - In preparation for a treatment guideline for suitable vascular access repair in
      Japan.
AB  - In cases of vascular access (VA) for hemodialysis including arteriovenous fistula
      and arteriovenous graft, venipuncture and hemostasis are usually repeated three
      times a week. Accordingly, it is assumed that VA vascular disorders are worsened
      following long-term hemodialysis. In particular, angiostenosis frequently occurs
      and results in insufficient blood flow or increased venous pressure.
      Additionally, stenosis is a major cause of VA occlusion. While VA intervention
      treatment is mainstream for VA stenosis, its major advantage lies in its less
      invasiveness because it is a percutaneous treatment. A further advantage of this
      treatment procedure is that the existing VA can be preserved intact. For
      practical use of VA intervention treatment, however, compliance with the
      therapeutic indication guideline is required. In K/DOQI of the United States,
      such a guideline has already been formulated based on evidence and specialist
      opinion, while the guideline of the European Vascular Access Society is presented
      in the form of a flowchart. The Japanese Society for Dialysis Therapy is
      currently preparing a guideline for the construction and maintenance of VA, which
      introduces the timing and principles of repair of VA in the following six
      categories: (i) stenosis; (ii) occlusion; (iii) venous hypertension; (iv) steal
      syndrome; (v) excess blood flow; and (vi) infection. Except for infection, most
      of the treatments for these events involve VA intervention, thus the need for the
      guideline for VA intervention treatment is becoming widely recognized.

PMID- 16911191
TI  - Biocompatibility of peritoneal dialysis fluid and influence of compositions on
      peritoneal fibrosis.
AB  - Conventional peritoneal dialysis fluid (PDF) is a bioincompatible solution
      because of several components. These unphysiological compositions might
      contribute to the development of peritoneal fibrosis. In the present overview we
      summarize the influence of each composition of PDF (acidic pH, high concentration
      of glucose and glucose degradation products; advanced glycation end-products and
      lactate) on the peritoneal fibrotic changes in long peritoneal dialysis (PD)
      patients. We also summarized the report of new approaches to the prevention of
      peritoneal fibrosis in Japan.

PMID- 16911192
TI  - Analysis of hemodynamics during blood purification therapy using a newly
      developed noninvasive continuous monitoring method.
AB  - Advancement in blood purification therapy extends not only to consoles and
      dialyzers, but also to patient management during blood purification therapy.
      However, no monitor has been devised for hemodynamics during blood purification
      therapy that is carried out continuously and non-invasively. By studying the
      laser Doppler flowmeter (LDF), we have developed a probe that can continuously
      measure changes in blood flow in tissues of the head and lower extremities during
      blood purification therapy. By applying the improved LDF, we have developed a non
      invasive continuous monitoring method (NICOMM). Hemodynamics in various types of
      blood purification therapies were also studied by simultaneously measuring with
      an automatic oscillometric sphygmomanometer.

PMID- 16911194
TI  - Chloroplast microsatellites reveal colonization and metapopulation dynamics in
      the Canary Island pine.
AB  - Chloroplast microsatellites are becoming increasingly popular markers for
      population genetic studies in plants, but there has been little focus on their
      potential for demographic inference. In this work the utility of chloroplast
      microsatellites for the study of population expansions was explored. First, we
      investigated the power of mismatch distribution analysis and the F(S) test with
      coalescent simulations of different demographic scenarios. We then applied these
      methods to empirical data obtained for the Canary Island pine (Pinus
      canariensis). The results of the simulations showed that chloroplast
      microsatellites are sensitive to sudden population growth. The power of the F(S)
      test and accuracy of demographic parameter estimates, such as the time of
      expansion, were reduced proportionally to the level of homoplasy within the data.
      The analysis of Canary Island pine chloroplast microsatellite data indicated
      population expansions for almost all sample localities. Demographic expansions at
      the island level can be explained by the colonization of the archipelago by the
      pine, while population expansions of different ages in different localities
      within an island could be the result of local extinctions and recolonization
      dynamics. Comparable mitochondrial DNA sequence data from a parasite of P.
      canariensis, the weevil Brachyderes rugatus, supports this scenario, suggesting a
      key role for volcanism in the evolution of pine forest communities in the Canary
      Islands.

PMID- 16911195
TI  - Patterns of genetic connectivity among anchialine habitats: a case study of the
      endemic Hawaiian shrimp Halocaridina rubra on the island of Hawaii.
AB  - Anchialine habitats, landlocked bodies of mixohaline water that fluctuate with
      the tides but have no surface connection to the sea, are known from around the
      world. Many anchialine organisms have widespread distributions and it has been
      hypothesized that high levels of gene flow and low levels of genetic
      differentiation are characteristic of populations from these habitats. However,
      the generality of this hypothesis requires further assessment, particularly in
      light of the significant negative impact these habitats and their biota have
      experienced from anthropogenic causes. This study investigated the population
      structure and demography of an endemic Hawaiian anchialine species, the atyid
      shrimp Halocaridina rubra, using mitochondrial cytochrome c oxidase subunit I
      (COI) gene sequences. A survey of 305 individuals from 16 populations collected
      on the island of Hawaii revealed 135 haplotypes. These haplotypes belonged to one
      of two divergent (2.7-4.9%) lineages; notably, no haplotypes were shared between
      the two coasts of the island. Along each coast, strong subdivision and little to
      no gene flow occurs between populations separated by > 30 km. The population
      structure and demography of H. rubra on Hawaii are influenced by regional
      hydrology, geology, volcanism and two distinct colonization events of the island.
      Thus, H. rubra on Hawaii demonstrates that populations of endemic anchialine
      organisms may exhibit significant levels of genetic structure and restricted
      levels of gene flow over limited geographic scales. This report brings novel
      insight into the biology of anchialine organisms and has important implications
      for the future management of these habitats and their biota.

PMID- 16911198
TI  - Population genetic structure of Arabidopsis lyrata in Europe.
AB  - Population genetic theory predicts that the self-incompatible and perennial herb,
      Arabidopsis lyrata, will have a genetic structure that differs from the self
      fertilizing, annual Arabidopsis thaliana. We quantified the genetic structure for
      eight populations of A. lyrata ssp. petraea in historically nonglaciated regions
      of central Europe. Analysis of 20 microsatellite loci for 344 individuals
      demonstrated that, in accordance with predictions, diploid populations had high
      genome-wide heterozygosity (H(O) = 0.48; H(E) = 0.52), high within-population
      diversity (83% of total) compatible with mutation-drift equilibrium, and moderate
      differentiation among populations (F(ST) = 0.17). Within a single population, the
      vast majority of genetic variability (92%) was found at the smallest spatial
      scale (< 3 m). Although there was no evidence of biparental inbreeding or clonal
      propagation at this scale (F(IS) = 0.003), significant fine-scale spatial
      autocorrelation indicated localized gene flow presumably due to gravity dispersed
      seeds (Sp = 0.018). Limited gene flow between isolated population clusters
      (regions) separated by hundreds of kilometres has given rise to an isolation by
      distance pattern of diversification, with low, but significant, differentiation
      among regions (F(ST) = 0.05). The maintenance of geographically widespread
      polymorphisms and uniformly high diversity throughout central Europe is
      consistent with periglacial survival of A. lyrata ssp. petraea north of the Alps
      in steppe-tundra habitats during the last glacial maximum. As expected of
      northern and previously glaciated localities, A. lyrata in Iceland was
      genetically less diverse and highly differentiated from central Europe (H(E) =
      0.37; F(ST) = 0.27).

PMID- 16911197
TI  - Phylogeny and biogeography of Croton alabamensis (Euphorbiaceae), a rare shrub
      from Texas and Alabama, using DNA sequence and AFLP data.
AB  - Croton alabamensis (Euphorbiaceae s.s.) is a rare plant species known from
      several populations in Texas and Alabama that have been assigned to var. texensis
      and var. alabamensis, respectively. We performed maximum parsimony, maximum
      likelihood, and Bayesian analyses of DNA sequences from the nuclear ribosomal
      internal transcribed spacer (ITS) and 5.8S regions and chloroplast trnL-trnF
      regions from collections of the two varieties of C. alabamensis and from outgroup
      taxa. C. alabamensis emerges alone on a long branch that is sister to Croton
      section Corylocroton and the Cuban endemic genus Moacroton. Molecular clock
      analysis estimates the split of C. alabamensis from its closest relatives in
      sect. Corylocroton at 41 million years ago, whereas the split of the two
      varieties of C. alabamensis occurred sometime in the Quaternary. Amplified
      fragment length polymorphism (AFLP) analyses were performed using two selective
      primer pairs on a larger sampling of accessions (22 from Texas, 17 from Alabama)
      to further discriminate phylogenetic structure and quantify genetic diversity.
      Using both neighbour joining and minimum evolution, the populations from the
      Cahaba and Black Warrior watersheds in Alabama form two well-separated groups,
      and in Texas, geographically distinct populations are recovered from Fort Hood,
      Balcones Canyonlands, and Pace Bend Park. Most of the molecular variance is
      accounted for by variance within populations. Approximately equal variance is
      found among populations within states and between states (varieties). Genetic
      distance between the Texas populations is significantly less than genetic
      distance between the Alabama populations. Both sequence and AFLP data support the
      same relationships between the varieties of C. alabamensis and their outgroup,
      while the AFLP data provide better resolution among the different geographical
      regions where C. alabamensis occurs. The conservation implications of these
      findings are discussed.

PMID- 16911199
TI  - Can common species provide valuable information for conservation?
AB  - To demonstrate the importance of genetic data for multispecies conservation
      approaches, we examined the distribution of genetic variation across the range of
      the mountain whitefish (Prosopium williamsoni) at microsatellite and allozyme
      loci. The mountain whitefish is a common species that is particularly well suited
      for accurately revealing historical patterns of genetic structure and differs
      markedly from previously studied species in habitat requirements and life history
      characteristics. As such, comparing the population genetic structure of other
      native fishes to similar data from mountain whitefish could inform management and
      conservation strategies. Genetic variation for mountain whitefish was
      hierarchically distributed for both allozymes and microsatellites. We found
      evidence for a total of five major genetically differentiated assemblages and we
      observed subdivision among populations within assemblages that generally
      corresponded to major river basins. We observed little genetic differentiation
      within major river basins. Geographic patterns of genetic differentiation for
      mountain whitefish were concordant with other native species in several
      circumstances, providing information for the designation of conservation units
      that reflect concordant genetic differentiation of multiple species. Differences
      in genetic patterns between mountain whitefish and other native fishes reflect
      either differences in evolutionary histories of the species considered or
      differences in aspects of their ecology and life history. In addition, mountain
      whitefish populations appear to exchange genes over a much larger geographic
      scale than co-occurring salmonids and are likely to be affected differently by
      disturbances such as habitat fragmentation.

PMID- 16911200
TI  - Decoupled mitochondrial and chloroplast DNA population structure reveals Holocene
      collapse and population isolation in a threatened Mexican-endemic conifer.
AB  - Chihuahua spruce (Picea chihuahuana Martinez) is a montane subtropical conifer
      endemic to the Sierra Madre Occidental in northwestern Mexico. Range-wide
      variation was investigated using maternally inherited mitochondrial (mtDNA) and
      paternally inherited chloroplast (cpDNA) DNA markers. Among the 16 mtDNA regions
      analysed, only two mitotypes were detected, while the study of six cpDNA
      microsatellite markers revealed eight different chlorotypes. The average cpDNA
      diversity (H = 0.415) was low but much higher than that for mtDNA (H = 0). The
      distribution of mitotypes revealed two clear nonoverlapping areas (G(ST) = N(ST)
      = 1), one including northern populations and the second one including the
      southern and central stands, suggesting that these two regions may represent
      different ancestral populations. The cpDNA markers showed lower population
      differentiation (G(ST) = 0.362; R(ST) = 0.230), implying that the two ancestral
      populations continued to exchange pollen after their initial geographic
      separation. A lack of a phylogeographic structure was revealed by different
      spatial analyses of cpDNA (G(ST) > R(ST); and samova), and reduced cpDNA gene
      flow was noted among populations (Nm = 0.873). Some stands deviated significantly
      from the mutation-drift equilibrium, suggesting recent bottlenecks. Altogether,
      these various trends are consistent with the hypothesis of a population collapse
      during the Holocene warming and suggest that most of the modern P. chihuahuana
      populations are now effectively isolated with their genetic diversity essentially
      modelled by genetic drift. The conservation efforts should focus on most southern
      populations and on the northern and central stands exhibiting high levels of
      genetic diversity. Additional mtDNA sequence analysis confirmed that P.
      martinezii (Patterson) is not conspecific with P. chihuahuana, and thus deserves
      separate conservation efforts.

PMID- 16911196
TI  - Recombination and selection shape the molecular diversity pattern of nitrogen
      fixing Sinorhizobium sp. associated to Medicago.
AB  - We investigate the genetic structure and molecular selection pattern of a
      sympatric population of Sinorhizobium meliloti and Sinorhizobium medicae. These
      bacteria fix nitrogen in association with plants of the genus Medicago. A set of
      116 isolates were obtained from a soil sample, from root nodules of three groups
      of plants representing among-species, within-species and intraline diversity in
      the Medicago genus. Bacteria were characterized by sequencing at seven loci
      evenly distributed along the genome of both Sinorhizobium species, covering the
      chromosome and the two megaplasmids. We first test whether the diversity of host
      plants influence the bacterial diversity recovered. Using the same data set, we
      then analyse the selective pattern at each locus. There was no relationship
      between the diversity of Medicago plants that were used for sampling and the
      diversity of their symbionts. However, we found evidence of selection within each
      of the two main symbiotic regions, located on the two different megaplasmids.
      Purifying selection or a selective sweep was found to occur in the nod genomic
      region, which includes genes involved in nodulation specificity, whereas
      balancing selection was detected in the exo region, close to genes involved in
      exopolysaccharide production. Such pattern likely reflects the interaction
      between host plants and bacterial symbionts, with a possible conflict of interest
      between plants and cheater bacterial genotypes. Recombination appears to occur
      preferentially within and among loci located on megaplasmids, rather than within
      the chromosome. Thus, recombination may play an important role in resolving this
      conflict by allowing different selection patterns at different loci.

PMID- 16911201
TI  - Fine-scale genetic structure of life history stages in the food-deceptive orchid
      Orchis purpurea.
AB  - In natural plant populations, fine-scale spatial genetic structure can result
      from limited gene flow, selection pressures or historical events, but the role of
      each factor is in general hard to discern. One way to investigate the origination
      of spatial genetic structure within a plant population consists of comparing
      spatial genetic structure among different life history stages. In this study,
      spatial genetic structure of the food-deceptive orchid Orchis purpurea was
      determined across life history stages in two populations that were regenerating
      after many years of population decline. Based on demographic analyses (2001
      2004), we distinguished between recruits and adult plants. For both sites, there
      was no difference in the proportion of polymorphic loci and expected
      heterozygosity between life history stages. However, spatial autocorrelation
      analyses showed that spatial genetic structure increased in magnitude with life
      history stage. Weak or no spatial genetic structure was observed for recruits,
      whereas adult plants showed a pattern that is consistent with that found in other
      species with a predominantly outcrossing mating system. The observed differences
      between seedlings and adults are probably a consequence of changes in management
      of the two study sites and associated demographic changes in both populations.
      Our results illustrate that recurrent population crashes and recovery may
      strongly affect genetic diversity and fine-scale spatial genetic structure of
      plant populations.

PMID- 16911202
TI  - Population structure in a critically endangered arctic fox population: does
      genetics matter?
AB  - The arctic fox (Alopex lagopus) in Scandinavia is classified as critically
      endangered after having gone through a severe decline in population size in the
      beginning of the 20th century, from which it has failed to recover despite more
      than 65 years of protection. Arctic foxes have a high dispersal rate and often
      disperse over long distances, suggesting that there was probably little
      population differentiation within Scandinavia prior to the bottleneck. It is,
      however, possible that the recent decline in population size has led to a
      decrease in dispersal and an increase in population fragmentation. To examine
      this, we used 10 microsatellite loci to analyse genetic variation in 150 arctic
      foxes from Scandinavia and Russia. The results showed that the arctic fox in
      Scandinavia presently is subdivided into four populations, and that the Kola
      Peninsula and northwest Russia together form a large fifth population. Current
      dispersal between the populations seemed to be very low, but genetic variation
      within them was relatively high. This and the relative F(ST) values among the
      populations are consistent with a model of recent fragmentation within
      Scandinavia. Since the amount of genetic variation is high within the
      populations, but the populations are small and isolated, demographic
      stochasticity seems to pose a higher threat to the populations' persistence than
      inbreeding depression and low genetic variation.

PMID- 16911203
TI  - Deep genetic subdivision within a continuously distributed and highly vagile
      marine mammal, the Steller's sea lion (Eumetopias jubatus).
AB  - The Steller's sea lion Eumetopias jubatus is an endangered marine mammal that has
      experienced dramatic population declines over much of its range during the past
      five decades. Studies using mitochondrial DNA (mtDNA) have shown that an
      apparently continuous population includes a strong division, yielding two
      discrete stocks, western and eastern. Based on a weaker split within the western
      stock, a third Asian stock has also been defined. While these findings indicate
      strong female philopatry, a recent study using nuclear microsatellite markers
      found little evidence of any genetic structure, implying extensive paternal gene
      flow. However, this result was at odds with mark-recapture data, and both sample
      sizes and genetic resolution were limited. To address these concerns, we
      increased analytical power by genotyping over 700 individuals from across the
      species' range at 13 highly polymorphic microsatellite loci. We found a clear
      phylogenetic break between populations of the eastern stock and those of the
      western and Asian stocks. However, our data provide little support for the
      classification of a separate Asian stock. Our findings show that mtDNA
      structuring is not due simply to female philopatry, but instead reflects a
      genuine discontinuity within the range, with implications for both the
      phylogeography and conservation of this important marine mammal.

PMID- 16911204
TI  - Bayesian identification of admixture events using multilocus molecular markers.
AB  - Bayesian statistical methods for the estimation of hidden genetic structure of
      populations have gained considerable popularity in the recent years. Utilizing
      molecular marker data, Bayesian mixture models attempt to identify a hidden
      population structure by clustering individuals into genetically divergent groups,
      whereas admixture models target at separating the ancestral sources of the
      alleles observed in different individuals. We discuss the difficulties involved
      in the simultaneous estimation of the number of ancestral populations and the
      levels of admixture in studied individuals' genomes. To resolve this issue, we
      introduce a computationally efficient method for the identification of admixture
      events in the population history. Our approach is illustrated by analyses of
      several challenging real and simulated data sets. The software (baps),
      implementing the methods introduced here, is freely available at
      http://www.rni.helsinki.fi/~jic/bapspage.html.

PMID- 16911205
TI  - Detecting introgressive hybridization between free-ranging domestic dogs and wild
      wolves (Canis lupus) by admixture linkage disequilibrium analysis.
AB  - Occasional crossbreeding between free-ranging domestic dogs and wild wolves
      (Canis lupus) has been detected in some European countries by mitochondrial DNA
      sequencing and genotyping unlinked microsatellite loci. Maternal and unlinked
      genomic markers, however, might underestimate the extent of introgressive
      hybridization, and their impacts on the preservation of wild wolf gene pools. In
      this study, we genotyped 220 presumed Italian wolves, 85 dogs and 7 known hybrids
      at 16 microsatellites belonging to four different linkage groups (plus four
      unlinked microsatellites). Population clustering and individual assignments were
      performed using a Bayesian procedure implemented in structure 2.1, which models
      the gametic disequilibrium arising between linked loci during admixtures, aiming
      to trace hybridization events further back in time and infer the population of
      origin of chromosomal blocks. Results indicate that (i) linkage disequilibrium
      was higher in wolves than in dogs; (ii) 11 out of 220 wolves (5.0%) were likely
      admixed, a proportion that is significantly higher than one admixed genotype in
      107 wolves found previously in a study using unlinked markers; (iii) posterior
      maximum-likelihood estimates of the recombination parameter r revealed that
      introgression in Italian wolves is not recent, but could have continued for the
      last 70 (+/- 20) generations, corresponding to approximately 140-210 years.
      Bayesian clustering showed that, despite some admixture, wolf and dog gene pools
      remain sharply distinct (the average proportions of membership to wolf and dog
      clusters were Q(w) = 0.95 and Q(d) = 0.98, respectively), suggesting that
      hybridization was not frequent, and that introgression in nature is counteracted
      by behavioural or selective constraints.

PMID- 16911206
TI  - Measurement of biological information with applications from genes to landscapes.
AB  - Biological diversity is quantified for reasons ranging from primer design, to
      bioprospecting, and community ecology. As a common index for all levels, we
      suggest Shannon's (S)H, already used in information theory and biodiversity of
      ecological communities. Since Lewontin's first use of this index to describe
      human genetic variation, it has been used for variation of viruses, splice
      junctions, and informativeness of pedigrees. However, until now there has been no
      theory to predict expected values of this index under given genetic and
      demographic conditions. We present a new null theory for (S)H at the genetic
      level, and show that this index has advantages including (i) independence of
      measures at each hierarchical level of organization; (ii) robust estimation of
      genetic exchange over a wide range of conditions; (iii) ability to incorporate
      information on population size; and (iv) explicit relationship to standard
      statistical tests. Utilization of this index in conjunction with other existing
      indices offers powerful insights into genetic processes. Our genetic theory is
      also extendible to the ecological community level, and thus can aid the
      comparison and integration of diversity at the genetic and community levels,
      including the need for measures of community diversity that incorporate the
      genetic differentiation between species.

PMID- 16911207
TI  - Phylogeography and genetic structure of Hibiscus tiliaceus--speciation of a
      pantropical plant with sea-drifted seeds.
AB  - Phylogenetic relationships and the spatial genetic structure of a pantropical
      plant with sea-drifted seeds, Hibiscus tiliaceus L., and its allied species were
      investigated. The combined distribution range of these species is over almost the
      entire littoral area of the tropics worldwide, which might result from the
      dispersal of their sea-drifted seeds and from recurrent speciation in local
      populations. A phylogenetic tree constructed using the nucleotide sequences of a
      c. 7500-bp portion of chloroplast DNA suggested the possibility that recurrent
      speciation from H. tiliaceus has given rise to all of its allied species. Three
      major sequence haplotypes of H. tiliaceus had wide and overlapping distributions
      throughout the Pacific, Atlantic and Indian Ocean regions. This distribution
      pattern was also confirmed by PCR-SSCP (polymerase chain reaction amplification
      with single-strand conformation polymorphism) and PCR-SSP (PCR amplification with
      sequence specific primers) analyses performed on more than 1100 samples from 65
      populations worldwide. Statistical analysis using F(ST) and analysis of molecular
      variance did not show significant genetic differentiation among the H. tiliaceus
      populations in the three oceanic regions. The results reported here suggested
      substantial gene flow occurred between populations in the different oceanic
      regions due to sea-drifted seeds. A strong genetic difference between the Pacific
      and Atlantic populations of Hibiscus pernambucensis Arruda was observed, which
      indicates that gene flow in this species between the two regions has been
      prevented. The wide and dominant distribution of a haplotype shared by H.
      pernambucensis and H. tiliaceus in the Atlantic region suggests significant
      introgression between the two species in this region.

PMID- 16911208
TI  - Evolution of Mesobuthus gibbosus (Brulle, 1832) (Scorpiones: Buthidae) in the
      northeastern Mediterranean region.
AB  - Sequence data derived from two mitochondrial markers, 16S rRNA and COI genes,
      were used to infer the evolutionary history of 47 insular and mainland
      populations covering most of the distributional range of the northeastern
      Mediterranean scorpion species Mesobuthus gibbosus. Based on the estimated
      divergence times of Mesobuthus lineages, the temporal frame of the genus
      differentiation in the northeastern Mediterranean region is placed in middle
      Miocene (15 million years ago). The biogeographic affinities of M. gibbosus
      populations point towards a mainly vicariant pattern of differentiation of the
      species which is consistent with the geological events that transformed the
      Aegean region during the period from 12 to 5 million years ago. M. gibbosus is an
      old northeastern Mediterranean species that has retained valuable bits of genetic
      information, reflecting some of the oldest vicariant events that have occurred in
      the area. Most importantly, the history witnessed by M. gibbosus has not been
      obscured by more recent palaeoevents of the region. Therefore, the case of M.
      gibbosus is in favour of a taxon-oriented 'perception' of the natural history of
      a given area.

PMID- 16911209
TI  - Global migration patterns in the fungal wheat pathogen Phaeosphaeria nodorum.
AB  - The global migration patterns of the fungal wheat pathogen Phaeosphaeria nodorum
      were analysed using 12 microsatellite loci. Analysis of 693 isolates from nine
      populations indicated that the population structure of P. nodorum is
      characterized by high levels of genetic diversity and a low degree of subdivision
      between continents. To determine whether genetic similarity of populations was a
      result of recent divergence or extensive gene flow, the microsatellite data were
      analysed using an isolation-with-migration model. We found that the continental
      P. nodorum populations diverged recently, but that enough migration occurred to
      reduce population differentiation. The migration patterns of the pathogen
      indicate that immigrants originated mainly from populations in Europe, China and
      North America.

PMID- 16911210
TI  - The recent history and population structure of five Mandarina snail species from
      subtropical Ogasawara (Bonin Islands, Japan).
AB  - The effect of Pleistocene climate change on the organisms of tropical and
      subtropical regions is rather poorly understood. We therefore studied the land
      snail genus Mandarina (Bradybaenidae) of oceanic Ogasawara (Bonin Islands,
      Japan), with the aim of using population genetic data to understand their recent
      history. Our analysis of a mitochondrial 16S ribosomal RNA region from more than
      600 snails in five ground-living species suggests that populations on the small
      islands of Mukoujima, Anejima, Imotojima and Meijima, as well as on the low-lying
      southern and central parts of Hahajima, have probably undergone recent
      bottlenecks followed by subsequent expansions. Except between the main island of
      Hahajima and Mukouijima, there is almost no evidence for gene flow among islands
      even though the islands were connected repeatedly by land bridges through the
      Pleistocene. Within islands the population structure is severe, suggestive of a
      long-term, low level of gene flow (F(ST) is frequently greater than 0.5 among
      geographically close populations). Finally, there is a marked genetic patchiness,
      meaning that genetically close populations are sometimes separated by genetically
      distant populations. These patterns could be a consequence of expansion from
      bottlenecks, low active dispersal and founder effects caused by rare long
      distance migrants. Unfortunately, the exact nature of the refugia and bottlenecks
      remains unknown because the palaeoclimate of this region is poorly understood.
      Dating the population size changes is also challenging because the molecular
      clock is uncertain. We suggest, however, that arid conditions or deforestation
      induced by decreased atmospheric CO(2) may have been the main factor in
      determining population size.

PMID- 16911211
TI  - Divergence and diversity: lessons from an arctic-alpine distribution (Pardosa
      saltuaria group, Lycosidae).
AB  - The relationship of interpopulation genetic divergence and within-population
      diversity has been studied for many temperate species in Europe, but not for the
      cold-adapted fauna. Here we present the first European-wide phylogeographical
      study of an arctic-alpine distribution in invertebrates, focusing on wolf spiders
      of the Pardosa saltuaria group. One hundred twenty-seven (127) specimens from 14
      populations were examined. Within Europe, these populations were distributed
      among six high mountain ranges and Scandinavia. We sequenced the whole 921 base
      pair mitochondrial (mt) ND1 gene. The resulting 55 unique haplotypes form three
      monophyletic phylogroups of deep divergence: a Pyrenean, a Balkan and a
      'northern' clade. Genetic distances (3.6-4.0%) between the major clades indicate
      that the arctic-alpine range disjunction was initiated by vicariance events,
      which precede the four major Alpine glaciations. However, low divergence and
      incomplete lineage sorting within the 'northern clade' suggest a late Pleistocene
      separation of the Alpine, Scandinavian, Carpathian and Sudetian populations.
      Thus, we provide evidence for a multiglacial origin of arctic-alpine
      distributions in Europe, i.e. the current disjunction results from range
      fragmentation in several glacial cycles. The pattern of genetic diversity within
      populations seems predominantly determined by historical factors, but is modified
      by contemporary aspects. Overall, diversity and divergence are negatively
      correlated. We suggest that low diversity values might result from (i) ancient
      bottlenecking during warm interglacial periods, as seen in the Pyrenees and
      Balkans; (ii) recent bottlenecking in small modern areas, as seen in the Giant
      Mountains and Bohemian Forest; and (iii) dispersal bottlenecking in northern
      Scandinavia.

PMID- 16911213
TI  - Phylogeography of the Percichthyidae (Pisces) in Patagonia: roles of orogeny,
      glaciation, and volcanism.
AB  - We used molecular evidence to examine the roles that vicariance mechanisms
      (mountain-building and drainage changes during the Pleistocene) have played in
      producing phylogeographical structure within and among South American fish
      species of the temperate perch family Percichthyidae. The percichthyids include
      two South American genera, Percichthys and Percilia, each containing several
      species, all of which are endemic to southern Argentina and Chile (Patagonia).
      Maximum-likelihood phylogenies constructed using mitochondrial DNA (mtDNA)
      control region haplotypes and nuclear GnRH3-2 intron allele sequences support the
      current taxonomy at the genus level (both Percichthys and Percilia form strongly
      supported, monophyletic clades) but indicate that species-level designations need
      revision. Phylogeographical patterns at the mtDNA support the hypothesis that the
      Andes have been a major barrier to gene flow. Most species diversity occurs in
      watersheds to the west of the Andes, together with some ancient divergences among
      conspecific populations. In contrast, only one species (Percichthys trucha) is
      found east of the Andes, and little to no phylogeographical structure occurs
      among populations in this region. Mismatch analyses of mtDNA sequences suggest
      that eastern populations last went through a major bottleneck c. 188 000 bp, a
      date consistent with the onset of the penultimate and largest Pleistocene
      glaciation in Patagonia. We suggest that eastern populations have undergone
      repeated founder-flush events as a consequence of glacial cycles, and that the
      shallow phylogeny is due to mixing during recolonization periods. The area of
      greater diversity west of the Andes lies outside the northern limit of the
      glaciers. mtDNA mismatch analysis of the genus Percilia which is restricted to
      this area suggests a long-established population at equilibrium. We conclude that
      patterns of genetic diversity in these South American genera have been primarily
      influenced by barriers to gene flow (Andean orogeny, and to a lesser extent,
      isolation in river drainages), and by glacial cycles, which have resulted in
      population contraction, re-arrangement of some watersheds, and the temporary
      breakdown of dispersal barriers among eastern river systems.

PMID- 16911212
TI  - Apparent 'sympatric' speciation in ecologically similar herbivorous beetles
      facilitated by multiple colonizations of an island.
AB  - Coexistence of recently diverged and ecologically similar sister species in
      complete sympatry represents a particularly compelling case for sympatric
      speciation. This study investigates the possible sympatric origin of two
      coexisting bark beetle taxa that utilize the same host plant on the island of La
      Palma in the Canary Islands. Aphanarthrum subglabrum and Aphanarthrum glabrum
      ssp. nudum breed inside dead twigs of Euphorbia lamarckii plants and are closely
      related to the allopatric A. glabrum ssp. glabrum in Tenerife, El Hierro and La
      Gomera. We tested the various speciation hypotheses in a genealogical context,
      using mitochondrial gene fragments from Cytochrome Oxidase I and 16S, and nuclear
      gene fragments from Enolase, Elongation Factor 1alpha and Histone H3.
      Phylogenetic analyses of the combined nuclear DNA data strongly supported a
      sister relationship between two sympatric and reproductively isolated taxa in La
      Palma. However, network analyses of subdivided nonrecombinant segments of the
      Enolase locus indicated a closer relationship between the two allopatric A.
      glabrum subspecies, suggesting multiple colonizations of this island. A bimodal
      distribution of mtDNA haplotypes in La Palma further documented the independent
      colonization of this island, with asymmetric introgression of mtDNA between two
      lineages. Consequently, the sympatric origin of the La Palma species is concluded
      to have involved allopatric phases before the parallel colonization of this
      island and subsequent introgression at some loci. The clear genetic and
      morphological evidence for reproductive isolation between these species suggests
      that the sympatric completion of divergence was either due to initial genetic
      incompatibility, morphological character displacement in male genitalia, or a
      combination of these factors.

PMID- 16911214
TI  - Comparative phylogeography of Ponto-Caspian mysid crustaceans: isolation and
      exchange among dynamic inland sea basins.
AB  - The distributions of many endemic Ponto-Caspian brackish-water taxa are
      subdivided among the Black, Azov and Caspian Sea basins and further among river
      estuaries. Of the two alternative views to explain the distributions, the relict
      school has claimed Tertiary fragmentation of the once contiguous range by
      emerging geographical and salinity barriers, whereas the immigration view has
      suggested recolonization of the westerly populations from the Caspian Sea after
      extirpation during Late Pleistocene environmental perturbations. A study of
      mitochondrial (COI) phylogeography of seven mysid crustacean taxa from the genera
      Limnomysis and Paramysis showed that both scenarios can be valid for different
      species. Four taxa had distinct lineages related to the major basin subdivision,
      but the lineage distributions and depths of divergence were not concordant. The
      data do not support a hypothesis of Late Miocene (10-5 Myr) vicariance; rather,
      range subdivisions and dispersal from and to the Caspian Sea seem to have
      occurred at different times throughout the Pleistocene. For example, in Paramysis
      lacustris each basin had an endemic clade 2-5% diverged from the others, whereas
      Paramysis kessleri from the southern Caspian and the western Black Sea were
      nearly identical. Species-specific ecological characteristics such as vagility
      and salinity tolerance seem to have played important roles in shaping the
      phylogeographic patterns. The mitochondrial data also suggested recent, human
      mediated cryptic invasions of P. lacustris and Limnomysis benedeni from the
      Caspian to the Sea of Azov basin via the Volga-Don canal. Cryptic species-level
      subdivisions were recorded in populations attributed to Paramysis baeri, and
      possibly in P. lacustris.

PMID- 16911215
TI  - Fat-tailed gene flow in the dioecious canopy tree species Fraxinus mandshurica
      var. japonica revealed by microsatellites.
AB  - Pollen flow, seed dispersal and individual reproductive success can be
      simultaneously estimated from the genotypes of adults and offspring using
      stochastic models. Using four polymorphic microsatellite loci, gene flow of the
      wind-pollinated and wind-seed-dispersed dioecious tree species, Fraxinus
      mandshurica var. japonica, was quantified in a riparian forest, in northern
      Japan. In a 10.5-ha plot, 74 female adults, 76 male adults and 292 current-year
      seedlings were mapped and genotyped, together with 200 seeds. To estimate
      dispersal kernels of pollen and seeds, we applied normal, exponential power,
      Weibull, bivariate t-distribution kernels, and two-component models consisting of
      two normal distribution functions, one with a small and one with a large
      variance. A two-component pollen flow model with a small contribution (26.1%)
      from short-distance dispersal (sigma = 7.2 m), and the rest from long-distance
      flow (sigma = 209.9 m), was chosen for the best-fitting model. The average
      distance that integrated pollen flows inside and outside the study plot was
      estimated to be 196.8 m. Tree size and flowering intensity affected reproduction,
      and there appeared to be critical values that distinguished reproductively
      successful and unsuccessful adults. In contrast, the gene flow model that
      estimated both pollen and seed dispersal from established seedlings resulted in
      extensive seed dispersal, and the expected spatial genetic structures did not
      satisfactorily fit with the observations, even for the selected model. Our
      results advanced small-scale individual-based parentage analysis for quantifying
      fat-tailed gene flow in wind-mediated species, but also clarified its limitations
      and suggested future possibilities for gene flow studies.

PMID- 16911216
TI  - Restricted mating dispersal and strong breeding group structure in a mid-sized
      marsupial mammal (Petrogale penicillata).
AB  - Ecological genetic studies have demonstrated that spatial patterns of mating
      dispersal, the dispersal of gametes through mating behaviour, can facilitate
      inbreeding avoidance and strongly influence the structure of populations,
      particularly in highly philopatric species. Elements of breeding group dynamics,
      such as strong structuring and sex-biased dispersal among groups, can also
      minimize inbreeding and positively influence levels of genetic diversity within
      populations. Rock-wallabies are highly philopatric mid-sized mammals whose strong
      dependence on rocky terrain has resulted in series of discreet, small colonies in
      the landscape. Populations show no signs of inbreeding and maintain high levels
      of genetic diversity despite strong patterns of limited gene flow within and
      among colonies. We used this species to investigate the importance of mating
      dispersal and breeding group structure to inbreeding avoidance within a 'small'
      population. We examined the spatial patterns of mating dispersal, the extent of
      kinship within breeding groups, and the degree of relatedness among brush-tailed
      rock-wallaby breeding pairs within a colony in southeast Queensland. Parentage
      data revealed remarkably restricted mating dispersal and strong breeding group
      structuring for a mid-sized mammal. Breeding groups showed significant levels of
      female kinship with evidence of male dispersal among groups. We found no evidence
      for inbreeding avoidance through mate choice; however, anecdotal data suggest the
      importance of life history traits to inbreeding avoidance between first-degree
      relatives. We suggest that the restricted pattern of mating dispersal and strong
      breeding group structuring facilitates inbreeding avoidance within colonies.
      These results provide insight into the population structure and maintenance of
      genetic diversity within colonies of the threatened brush-tailed rock-wallaby.

PMID- 16911217
TI  - Gregariousness and protandry promote reproductive insurance in the invasive
      gastropod Crepidula fornicata: evidence from assignment of larval paternity.
AB  - According to the size-advantage hypothesis, protandric sequential hermaphroditism
      is expected when the increase in reproductive success with age or size is small
      for males but large for females. Interestingly, some protandrous molluscs have
      developed gregarious strategies that might enhance male reproductive success but
      at the cost of intraspecific competition. The gastropod Crepidula fornicata, a
      European invading species, is ideal for investigating mating patterns in a
      sequential hermaphrodite in relation to grouping behaviour because individuals of
      different size (age) live in perennial stacks, fertilization is internal and
      embryos are brooded. Paternity analyses were undertaken in stacks sampled in
      three close and recently invaded sites in Brittany, France. Paternity assignment
      of 239 larvae, sampled from a set of 18 brooding females and carried out using
      five microsatellite loci, revealed that 92% of the crosses occurred between
      individuals located in the same stack. These stacks thus function as independent
      mating groups in which individuals may reproduce consecutively as male and female
      over a short time period, a pattern explained by sperm storage capacity.
      Gregariousness and sex reversal are promoting reproductive insurance in this
      species. In addition, females are usually fertilized by several males (78% of the
      broods were multiply sired) occupying any position within the stack, a result
      reinforcing the hypothesis of sperm competition. Our study pointed out that
      mating behaviours and patterns of gender allocation varied in concert across
      sites suggesting that multiple paternities might enhance sex reversal depending
      on sperm competition intensity.

PMID- 16911218
TI  - Mating system and reproductive success in eastern Pacific harbour seals.
AB  - Harbour seals sometimes breed along inland travel corridors where females become
      clustered in space and time and males establish underwater acoustic display
      territories similar to terrestrial arenas known as resource-based leks. Under
      these conditions, we predicted that higher levels of polygyny would be observed
      than has been previously reported for this species mating in open coast
      environments without travel corridors. Reproductive success (RS) of 70 males was
      measured using 20 microsatellite DNA loci and likelihood-based paternity analysis
      of 136 offspring collected over 3 years. Most males were assigned either zero or
      one paternity with 80% confidence. The greatest number of pups assigned to one
      male in a season was two. Variance in RS was higher for males than females (which
      are biologically limited to one offspring per year) indicating low to mild
      polygyny. In addition, distributions of relatedness values among pups within year
      classes did not differ significantly from a simulated distribution with R = 0,
      indicating that half-siblings were uncommon. Overall, polygyny levels were low
      relative to terrestrial pinniped mating systems and similar to observations from
      a harbour seal population along an open coast. Due to large confidence intervals
      associated with our results, we cannot rule out the hypothesis that a travel
      corridor might increase the degree of polygyny skew relative to that observed in
      open coast environments. Habitat appeared to influence male strategies as the
      most successful males in open coast environments patrolled offshore, while the
      most successful male in this study defended a territory along the travel
      corridor.

PMID- 16911219
TI  - Long-term paternity skew and the opportunity for selection in a mammal with
      reversed sexual size dimorphism.
AB  - Most mammalian groups are characterized by male-biased sexual size dimorphism, in
      which size-dependent male-male competition and reproductive skew are tightly
      linked. By comparison, little is known about the opportunity for sexual selection
      in mammalian systems without male-biased dimorphism, where the traits under
      sexual selection might be less obvious. We examined 10 years of parentage data in
      a colony of greater horseshoe bats (Rhinolophus ferrumequinum) to determine the
      magnitude of male reproductive skew and the opportunity for sexual selection in a
      mammal in which females are the larger sex. Annual paternity success was weakly
      skewed but consistent patterns led to strong longitudinal paternity skew among
      breeders. Just three males accounted for a third of all paternity assignments,
      representing at least a fifth of all colony offspring born in a decade. Paternity
      success was in part determined by age but was not influenced by dispersal status.
      Our results show that paternity skew and the opportunity for sexual selection in
      a species with reversed sexual size dimorphism can approach levels reported for
      classical examples of species with polygyny and male-biased dimorphism, even
      where the traits under sexual selection are not known.

PMID- 16911220
TI  - Comparison of gene expression in segregating families identifies genes and
      genomic regions involved in a novel adaptation, zinc hyperaccumulation.
AB  - One of the challenges of comparative genomics is to identify specific genetic
      changes associated with the evolution of a novel adaptation or trait. We need to
      be able to disassociate the genes involved with a particular character from all
      the other genetic changes that take place as lineages diverge. Here we show that
      by comparing the transcriptional profile of segregating families with that of
      parent species differing in a novel trait, it is possible to narrow down
      substantially the list of potential target genes. In addition, by assuming
      synteny with a related model organism for which the complete genome sequence is
      available, it is possible to use the cosegregation of markers differing in
      transcription level to identify regions of the genome which probably contain
      quantitative trait loci (QTLs) for the character. This novel combination of
      genomics and classical genetics provides a very powerful tool to identify
      candidate genes. We use this methodology to investigate zinc hyperaccumulation in
      Arabidopsis halleri, the sister species to the model plant, Arabidopsis thaliana.
      We compare the transcriptional profile of A. halleri with that of its sister
      nonaccumulator species, Arabidopsis petraea, and between accumulator and
      nonaccumulator F(3)s derived from the cross between the two species. We identify
      eight genes which consistently show greater expression in accumulator phenotypes
      in both roots and shoots, including two metal transporter genes (NRAMP3 and
      ZIP6), and cytoplasmic aconitase, a gene involved in iron homeostasis in mammals.
      We also show that there appear to be two QTLs for zinc accumulation, on
      chromosomes 3 and 7.

PMID- 16911221
TI  - Tracking factors modulating cytoplasmic incompatibilities 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. One Wolbachia host, Culex pipiens complex
      mosquitoes, displays high levels of variability in both CI crossing types
      (cytotypes) and DNA markers. We report here an analysis of 14 mosquito strains,
      containing 13 Wolbachia variants, and with 13 different cytotypes. Cytotypes were
      Wolbachia-dependent, as antibiotic treatment rendered all strains tested
      compatible. Cytotype distributions were independent of geographical distance
      between sampling sites and host subspecies, suggesting that Wolbachia does not
      promote a reproductive isolation depending on these parameters. Backcross
      analysis demonstrated a mild restoring effect of the nuclear genome, indicating
      that CI is mostly cytoplasmically determined for some crosses. No correlation was
      found between the phenotypic and genotypic variability of 16 WO prophage and
      transposon markers, except for the WO prophage Gp15 gene, which encodes a protein
      similar to a bacterial virulence factor. However, Gp15 is partially correlated
      with CI expression, suggesting that it could be just linked to a CI gene.

PMID- 16911222
TI  - DNA barcoding reveals extraordinary cryptic diversity in an amphipod genus:
      implications for desert spring conservation.
AB  - DNA barcoding has revealed unrecognized species in several animal groups. In this
      study we have employed DNA barcoding to examine Hyalella, a taxonomically
      difficult genus of amphipod crustaceans, from sites in the southern Great Basin
      of California and Nevada, USA. We assessed the extent of species diversity using
      a species screening threshold (SST) set at 10 times the average intrapopulation
      cytochrome c oxidase subunit I (COI) haplotype divergence. Despite the fact that
      this threshold approach is more conservative in delineating provisional species
      than the phylogenetic species concept, our analyses revealed extraordinary levels
      of cryptic diversity and endemism. The SST discriminated two provisional species
      within Hyalella sandra, and 33 provisional species within Hyalella azteca. COI
      nucleotide divergences among these provisional species ranged from 4.4% to 29.9%.
      These results have important implications for the conservation of life in desert
      springs - habitats that are threatened as a result of groundwater over
      exploitation.

PMID- 16911223
TI  - Medieval remains from Lithuania indicate loss of a mitochondrial haplotype in
      Bison bonasus.

PMID- 16911225
TI  - Global veterinary defence: where to from here veterinary science?

PMID- 16911226
TI  - Review of corynetoxins poisoning of livestock, a neurological disorder produced
      by a nematode-bacterium complex.

PMID- 16911227
TI  - Hydrops fetalis associated with pulmonary hypoplasia in Dexter calves.
AB  - The occurrence of severe fetal dystocia due to hydrops fetalis associated with
      pulmonary aplasia in two male and pulmonary hypoplasia in one female Australian
      Dexter fetuses from two herds is described. Obstetrical intervention by caesarean
      section was required for delivery of the fetuses, with mortalities in one dam and
      the 3 calves. Clinical, pathological and genetic features are tabulated to assist
      in distinguishing pulmonary hypoplasia-associated hydrops fetalis from the more
      prevalent disorder of chondrodysplasia in Dexter cattle. Anasarca and complete
      absence or presence of only rudimentary lung tissue in a large thoracic cavity
      clearly distinguishes this entity from the lesions of Dexter chondrodysplasia
      that include severe micromelia and abundant lung tissue in a small thoracic
      cavity with shortened spine and rib cage. Pedigree information suggested that
      Dexter hydrops may be transmitted in an autosomal recessive manner.

PMID- 16911228
TI  - Effect of monensin controlled release capsules on blood metabolites in
      periparturient dairy cows.

PMID- 16911229
TI  - Primary hypoparathyroidism in dogs: a retrospective study of 17 cases.
AB  - OBJECTIVE: To evaluate the clinico-pathological findings, response to treatment
      and prevalence of complications in dogs with primary hypoparathyroidism. DESIGN:
      Retrospective study of 17 dogs presenting to the University of Melbourne
      Veterinary Clinical Centre and Murdoch University Veterinary Hospital over a 15
      year period (1990 to 2004). Case records were evaluated for signalment, body
      weight, diet type, historical and clinical findings, serum total calcium,
      phosphate, albumin and parathyroid hormone concentrations, urinary fractional
      excretion ratios of calcium and phosphate, electrocardiogram (ECG) results,
      treatments administered, outcome and period of follow-up. RESULTS: The most
      common breeds identified were St Bernard (three dogs), Chihuahua (two dogs),
      German Shepherd (two dogs) and Jack Russell Terrier (two dogs). Three dogs were
      cross bred. Seizures, muscle tremors and fasciculations, stiff gait, tetany,
      muscle cramping, behavioural change and hyperventilation were the most common
      clinical signs. Vomiting, inappetence, diarrhoea, abdominal pain, hyperthermia,
      facial pruritus, ataxia, weakness, cataracts, and circling also occurred with
      less frequency. The mean duration of observed clinical signs preceding diagnosis
      was 33 days (median 13 days, range 1 to 173 days). All dogs had marked
      hypocalcaemia with normal or mildly increased serum albumin concentrations. Mean
      phosphate concentrations were significantly higher in inappetent dogs (P =
      0.049). Mean serum calcium concentrations were significantly lower in dogs with
      cataracts compared to those without (P = 0.046). There were no other significant
      relationships between serum calcium or phosphate concentrations and the clinical
      presentation or outcome. No significant correlations were identified between the
      presence of a particular clinical sign and the duration of clinical signs. ECGs
      were obtained in four dogs and all exhibited QT interval prolongation due to a ST
      segment prolongation. Sixteen of 17 dogs were treated successfully for
      hypocalcaemia and discharged from hospital. Acute management included parenteral
      calcium gluconate (10 dogs) and intravenous anticonvulsants (five dogs). Chronic
      therapy included oral vitamin D analogues and calcium supplementation. Treatment
      complications occurred in two dogs and included acute renal failure (one dog) and
      iatrogenic tissue necrosis following subcutaneous calcium administration (one
      dog). The mean follow-up period was 14.5 months (median 13 months, range 0 to 39
      months). Twelve dogs were alive at the last follow up and two dogs were
      euthanased for unrelated reasons. The type of vitamin D analogue used was not
      associated with outcome. CONCLUSION: Primary hypoparathyroidism was an uncommon
      diagnosis in dogs. Saint Bernards, cross bred dogs, German Shepherd dogs and
      Terrier breeds were most commonly affected. Neurological signs were the most
      common presenting clinical signs, although alimentary signs may have been more
      common than previously reported. Dogs with primary hypoparathyroidism appeared to
      have a good prognosis following initiation of calcium supplementation and vitamin
      D therapy. Complications of treatment were uncommon and could be minimised with
      regular monitoring.

PMID- 16911231
TI  - Death of two pups from spider envenomation.

PMID- 16911233
TI  - Placement of a long term tracheal cannula in a Thoroughbred racehorse with
      bilateral laryngeal dysfunction.
AB  - A Thoroughbred horse with bilateral laryngeal dysfunction was treated by
      placement of a long term tracheal cannula in order to restore full athletic
      function. The horse initially presented with right-sided arytenoid dysfunction
      that was considered to be due to a congenital malformation of the laryngeal
      cartilage. This was corrected by a right-sided laryngoplasty and ventriculectomy.
      The horse re-presented 1 year later with idiopathic left laryngeal hemiplegia.
      The decision was made to place a long-term tracheal cannula due to the low
      success rate and high complication rate associated with other surgeries used to
      correct bilateral arytenoid dysfunction. A three-piece tracheotomy cannula and
      stopper were positioned under general anaesthesia. The horse rapidly adjusted to
      the tracheal cannula and no post-surgical complications were encountered. The
      horse resumed training 4 weeks postoperatively. Due to the rules governing racing
      in Australia the horse was exported to New Zealand where he continued his racing
      career. It was concluded that tracheotomy is a straightforward technique
      associated with minimal complications and can provide an excellent prognosis for
      return of full airway function in racing horses. It is recognised that many
      issues need to be considered prior to more general acceptance of this technique,
      including assessment of animal welfare issues and public perception. In
      appropriate cases consideration should be given to using long term placement of a
      tracheotomy cannula as a treatment option to restore maximal airflow in horses
      with upper airway obstruction.

PMID- 16911234
TI  - Surgical treatment of extensive chondroid formation in the guttural pouch of a
      Warmblood horse.
AB  - A Warmblood horse presented with a purulent nasal discharge that had failed to
      respond to antibiotic therapy. Radiography and endoscopy confirmed a large number
      of chondroid masses (over 200) in the left guttural pouch. Despite the large
      number of chondroids present, there was no external swelling evident. The masses
      were surgically removed via a hyovertebrotomy approach that provided excellent
      exposure, and no postoperative complications were encountered. Long term follow
      up (3 years) confirmed a successful outcome.

PMID- 16911236
TI  - Salute, slainte and sante.

PMID- 16911237
TI  - Underestimation and overestimation of personal weight status: associations with
      socio-demographic characteristics and weight maintenance intentions.
AB  - OBJECTIVE: Unwarranted underestimation and overestimation of personal weight
      status may prevent weight maintenance behaviour. The present study reports on
      correlates of under- and overestimation of personal weight status and the
      association with weight maintenance intentions and self-reported action. DESIGN:
      Comparison of three cross-sectional surveys, representing different population
      groups. SUBJECTS: Survey 1: 1694 adolescents 13-19 years of age; survey 2: 979
      nonobese adults 25-35 years of age; survey 3: 617 adults 21-62 years of age.
      MEASUREMENTS: Self-administered written questionnaires (surveys 1 and 3) and
      telephone-administered questionnaires (survey 2); self-reported BMI, self-rated
      weight status, intentions and self-reported actions to avoid weight gain or to
      lose weight, sex, age, education and ethnic background. Respondents were
      classified as people who are realistic about personal body weight status or
      people who under- and overestimate their body weight status, based on BMI and
      self-rated weight status. RESULTS: Most respondents in the three survey
      populations were realistic about their weight status. Overestimation of weight
      status was consistently more likely among women, whereas underestimation was more
      likely among men, older respondents and respondents from ethnic minorities. Self
      rated weight status was a stronger correlate of intentions and self-report
      actions to avoid weight gain than weight status based on Body Mass Index.
      CONCLUSIONS: Relevant proportions of the study populations underestimated or
      overestimated their bodyweight status. Overestimation of personal weight status
      may lead to unwarranted weight maintenance actions, whereas underestimation may
      result in lack of motivation to avoid further weight gain.

PMID- 16911238
TI  - The effect of advice to walk 2000 extra steps daily on food intake.
AB  - BACKGROUND: It is currently unclear how physical activity and diet interact
      within the ranges of activity seen in the general population. This study aimed to
      establish whether a small, acute, increase in physical activity would lead to
      compensatory change in energy intake and nutrient balance, and to provide power
      analysis data for future research in this field. METHOD: Twelve participants were
      studied over 7 days of habitual activity and 2 weeks after instruction to
      increase physical activity by 2000 steps per day. Physical activity was assessed
      using a diary, the 'activPAL' activity monitor and a pedometer. Dietary analyses
      from prospective food diaries were compared between the first and third weeks.
      RESULTS: Participants increased step-counts (+2600 steps per day, P = 0.008) and
      estimated energy expenditure (+300-1000 kJ day(-1), P = 0.002) but did not
      significantly change their energy intake, dietary composition or number of meals
      per day. From reverse power analysis 38 participants would be needed to exclude a
      change in energy intake of 400 kJ day(-1) with 90% power at P < 0.05; 400 kJ day(
      1) would compensate for a 2000 steps per day increase in physical activity.
      CONCLUSION: These results did not demonstrate any compensatory increase in food
      consumption when physical activity was increased by walking an average of 2600
      additional steps per day. Power analysis indicates that a larger study (n = 38)
      will be necessary to exclude such an effect with confidence.

PMID- 16911239
TI  - Prepregnancy body mass index and dietary intake in the first trimester of
      pregnancy.
AB  - OBJECTIVES: Adequate maternal nutrition is of paramount importance in pregnancy,
      particularly in the first trimester when fetal development is crucial. It has
      been reported that heavier women are most likely to fear weight gain associated
      with pregnancy. Few studies have, however, investigated associations between
      prepregnancy body mass index (BMI) and nutrient intakes in the first trimester of
      gestation using detailed, prospective methodologies. The aim of this study was to
      investigate possible associations between prepregnancy BMI and nutrient intakes
      in the first trimester of gestation. DESIGN: Seventy-two Caucasian, primiparous
      nonsmokers of mean age 33.1 years (SD 4.6) were recruited from three London
      teaching hospitals and they completed a background information questionnaire and
      a 4- to 7-day weighed inventory food diary during the first trimester of
      pregnancy. Prepregnancy anthropometric data were extracted from General
      Practitioner records. RESULTS: Prepregnancy BMI was inversely associated with
      dietary energy (P = 0.04), Southgate and Englyst fibre (P < 0.01), and iron and
      folate (P < 0.01). After excluding under-reporters [individual energy
      intake:basal metabolic rate (estimated) ratio < 1.2], prepregnancy BMI was
      inversely associated with folate intake (P =0.04). Dietary intakes of Englyst
      fibre (P = 0.03) were statistically significantly lower than average dietary
      recommendations in this group. CONCLUSIONS: This study identified that women with
      a high prepregnancy BMI are more likely to under-report nutrient intakes. The
      finding that folate intake was significantly lower in heavier women accurately
      reporting dietary intake is of particular concern.

PMID- 16911240
TI  - Parent and child reports of fruit and vegetable intakes and related family
      environmental factors show low levels of agreement.
AB  - OBJECTIVE: The purpose of the present study was to determine the level of
      agreement between child and parent reports of 9- to 10-year-old children's
      consumption of fruit and vegetables and potential family-environmental
      determinants. METHODS: Schoolchildren and their parents completed parallel
      questionnaires at baseline and at follow-up (1 year later) about usual fruit and
      vegetable consumption of the child, potential determinants and general
      demographics. Matched child-parent couples were included in the analyses
      (baseline = 380; follow-up = 307). To assess the level of agreement between child
      and parent reports at both points in time, dependent-sample t-test, correlation
      coefficients, weighted Cohen's kappa coefficients and Bland-Altman plots
      including limits of agreement were used. RESULTS: Both at baseline and at follow
      up, the mean intake of fruit and vegetable reported by the children were
      significantly higher than reported by their parents, but differences were smaller
      at follow-up. Correlation coefficients between child and parent reports (0.28
      0.43) and weighted Cohen's kappa coefficients (0.25-0.28) were weak to moderate.
      Limits of agreement were wide. CONCLUSION: The agreement between parent and child
      reports is weak to moderate and may depend on the age of the child. Fourth
      graders may overestimate their own intake of fruit and vegetables.

PMID- 16911241
TI  - Processes underlying young women's decisions to eat fruits and vegetables.
AB  - OBJECTIVE: To relate the use of identified processes that college women use to
      eat enough fruits and enough vegetables to their stages of readiness to change
      and their fruit and vegetable (F/V) intakes. METHOD: A cross-sectional assessment
      of college women 18-24 years of age (n = 236) was conducted to assess stage of
      readiness to eat F/V. Use of seven processes, earlier confirmed in a separate
      sample of college students the same age (health concerns, self-reevaluation,
      social liberation, health commitment/action, interpersonal control, external
      reinforcement and helping relationships) was compared with stage of change for
      F/V and 3 days of dietary intakes. RESULTS: In these young college women, use of
      self-reevaluation, a cognitive process for change, peaked in the preparation
      stage for both F/V. Use of health commitment/action, a post-action process
      including counter-conditioning, peaked in those in action/maintenance for F/V.
      Weight concerns related to the counter-conditioning processes women used to eat
      more fruit. CONCLUSION: Health practitioners should focus on weight management,
      appearance and health benefits of eating fruits and vegetables for this
      demographic group.

PMID- 16911242
TI  - Encouraging fruit consumption in primary schoolchildren: a pilot study in North
      Wales, UK.
AB  - OBJECTIVE: To explore the feasibility and cost of promoting fruit consumption
      among primary schoolchildren across Anglesey, a region in North Wales, UK.
      DESIGN, SETTING AND SUBJECTS: A postal survey of the head teachers of all 51
      primary schools across Anglesey to ascertain their attitudes to promoting fruit
      consumption and current initiatives in place was conducted. This was followed by
      a 1-week pilot study in a single primary school to assess parents' support and
      willingness to bear or share costs, to determine children's fruit preferences,
      and to calculate fruit waste. Finally, the cost to local government of providing
      a piece of fruit to each primary schoolchild daily was calculated. RESULTS: A 53%
      response rate was obtained in the postal survey of primary school head teachers.
      All respondents expressed an interest in participating in future fruit promotion
      programmes. Of 27 primary schools, 26 that responded (96.3%) had programmes in
      place in which 18 had adopted specific food policies. In the pilot study at the
      single Anglesey primary school, a response rate of 97% from parents who expressed
      support for fruit promotion in school was obtained. Parents expressed their
      willingness to pay at least 15 pence per day towards fruit provision at break
      time for their children if such a service was not provided by local government.
      If local government was to invest in this initiative, the total cost of providing
      one piece of fruit per day to all primary school children in Anglesey would be
      211,000 pounds per annum (2004 prices; 19 pence per child per day). CONCLUSION:
      This pilot study shows support by teachers and parents for initiatives to
      encourage primary schoolchildren to eat more fruit. Waste can be minimized by
      choosing fruit that children prefer, in this study, grapes, apples and oranges.
      The decision as to whether local government or parents are asked to pay for fruit
      provision is political, depending on local socioeconomic circumstances, local
      government priorities, national education and nutrition policies.

PMID- 16911243
TI  - Differences in weaning practice, food and nutrient intake between breast- and
      formula-fed 4-month-old infants in England.
AB  - BACKGROUND: Breastfed infants may grow more slowly in the second half of infancy
      than formula-fed infants, differences in weaning practice may contribute.
      METHODS: Dietary intakes of 4-month-old infants have been investigated cross
      sectionally. Diet was assessed using a structured 1-day un-weighed dietary record
      in 852 white singletons (72% of those invited) from a random sub-sample of
      infants taking part in Avon Longitudinal Study of Parents and Children. Nutrient
      intakes of formula-fed infants were compared by sex and with UK reference values.
      Estimated mean energy and nutrient intakes, mean bodyweight and daily quantities
      of food consumed were compared by weaning practice. RESULTS: In formula-fed
      infants mean energy intakes and intakes of most nutrients were adequate. There
      were significant differences in intakes of most nutrients by weaning practice;
      however, mean energy intake and body weight of breastfed infants was similar to
      formula-fed infants. Infants given formula milk were less likely to consume
      vegetables and fruit, and more likely to consume commercial infant drinks,
      compared with infants who were breastfed. In breastfed infants breast milk intake
      was lower if solids were given (905 g versus 818 g; P = 0.01); however, nutrient
      intake was not compromised. In formula-fed infants milk intake was not different
      in those having solids compared to those having milk only (810 g versus 795 g; P
      = 0.649). CONCLUSIONS: Differences in weaning practice and patterns of food
      consumption were seen between breast- and formula-fed infants, these may
      contribute to later growth differences.

PMID- 16911246
TI  - Early phase training-induced muscular adaptations are related to oestrogen
      status.

PMID- 16911247
TI  - Vascular NO availability is an important determinant of impaired skeletal muscle
      microvascular PO in chronic heart failure.

PMID- 16911248
TI  - Muscle microvascular oxygenation in chronic heart failure: role of nitric oxide
      availability.
AB  - AIM: To test the hypothesis that diminished vascular nitric oxide availability
      might explain the inability of individuals with chronic heart failure (CHF) to
      maintain the microvascular PO(2)'s (PO(2mv) proportional, variant O(2) delivery
      to-uptake ratio) seen in healthy animals. METHODS: We superfused sodium
      nitroprusside (SNP; 300 microm), Krebs-Henseleit (control, CON) and L-nitro
      arginine methyl ester (L-NAME; 1.5 mM) onto the spinotrapezius muscle and
      measured PO(2mv) by phosphorescence quenching in female Sprague-Dawley rats (n =
      26) at rest and during twitch contractions (1 Hz). Seven rats served as controls
      (Sham) while CHF was induced by myocardial infarction. CHF rats were grouped as
      moderate (MOD; n = 15) and severe CHF (SEV; n = 4) according to morphological
      data and baseline PO(2mv). RESULTS: In contrast to Sham and MOD, L-NAME did not
      affect the PO(2mv) response (dynamics and steady-state) of SEV when compared with
      CON. SNP restored the PO(2mv) profile of SEV to that seen in Sham animals during
      CON. Specifically, the effect of L-NAME expressed as Delta(L-NAME - CON) were:
      Baseline PO(2mv) [in mmHg, DeltaSham = -7.0 +/- 1.6 (P < 0.05); DeltaSEV =-1.2 +/
      2.1], end-contractions PO(2mv) [in mmHg, DeltaSham = -5.0 +/- 1.0 (P < 0.05);
      DeltaSEV = -2.5 +/- 0.5] and time constant of PO(2mv) decrease [in s, DeltaSham =
      -6.5 +/- 3.0 (P < 0.05); DeltaSEV = -3.2 +/- 1.8]. CONCLUSION: These data provide
      the first direct evidence that the pathological profiles of PO(2mv) associated
      with severe CHF can be explained, in part, by a diminished vascular NO
      availability.

PMID- 16911249
TI  - Contribution of systemic arterial compliance and systemic vascular resistance to
      effective arterial elastance changes during exercise in humans.
AB  - BACKGROUND: Effective arterial elastance (Ea), an index of arterial load,
      increases with elevations in left ventricular elastance to maximize the
      efficiency of left ventricular stroke work during exercise. Systemic arterial
      compliance (C) and vascular resistance (R) are the primary components
      contributing to Ea, and R plays a greater role in determining Ea at rest. We
      hypothesized that the contribution of C to Ea increases during exercise to
      maintain an optimal balance between arterial load and ventricular elastance, and
      that the increase in Ea is due primarily to a reduction in C. AIM: The aim of
      this study was to investigate the contributions of C and R to Ea during exercise.
      METHODS: Ea (0.9 x systolic blood pressure/stroke volume), C (stroke volume/pulse
      pressure), R (mean blood pressure/cardiac output), and cardiac cycle length (T)
      were measured at rest and during exercise of 40%, 60% and 80% maximal oxygen
      uptake (O(2max)) using Doppler echocardiography in 45 healthy men. RESULTS: Ea
      did not differ between rest and 40%O(2max), but it was greater at 60% and
      80%O(2max). C markedly decreased during exercise in an exercise intensity
      dependent manner. The changes in R/T during exercise were small, whereas it
      decreased at 40%O(2max) and gradually increased at 60% and 80%O(2max).
      CONCLUSIONS: The present results suggest that the contribution of systemic
      arterial compliance to effective arterial elastance increases during exercise.
      Therefore, we propose that the increase in arterial load during exercise is
      mainly driven by a reduction in systemic arterial compliance.

PMID- 16911250
TI  - Hypotonic stress activates BK channels in clonal kidney cells via purinergic
      receptors, presumably of the P2Y subtype.
AB  - AIM: Membrane stretch due to cell swelling may cause a minute leakage of
      adenosine triphosphate (ATP) that stimulates endogenous purinergic receptors. The
      following elevation of the cytosolic-free Ca(2+) concentration ([Ca(2+)](i)) may
      then participate in cell volume regulation. The aim of the present study was to
      test if purinergic receptors and large conductance Ca(2+) activated K(+) (BK)
      channels are activated in response to hypotonic stress in clonal kidney cells
      (Vero cells). METHODS: The methods used are fura-2 microfluorometry, cell
      attached patch clamp and reverse-transcriptase polymerase chain reaction (RT
      PCR). METHODS: Subjecting cells to hypotonic stress for 10 s by exposure to a
      solution with 45% reduced osmolality induced a transient rise in [Ca(2+)](i).
      This response persisted in virtually Ca(2+)-free extracellular solution,
      demonstrating that Ca(2+) was mainly released from intracellular stores. The
      hypotonically induced elevation of [Ca(2+)](i) was completely inhibited by the P2
      receptor antagonists suramine (100 microM) and pyridoxalphosphate-6-azophenyl
      2'4'-disulphonate (PPADS; 20 microM), indicating that extracellular ATP is
      crucial for the [Ca(2+)](i) increase. RT-PCR revealed the expression of mRNA for
      P2Y(1) receptors in Vero cells. The putatively selective P2Y(1) antagonist PPADS
      did completely block Ca(2+) responses to both ATP and hypotonic stress,
      suggesting that P2Y(1) receptors are mediating the response. Furthermore, patch
      clamp recordings in cell-attached configuration revealed that BK channels are
      activated in response to hypotonic stress. conclusion: Vero cells express
      functional purinergic receptors, presumably of the P2Y(1) subtype. These
      receptors are responsible for the elevation of [Ca(2+)](i) evoked by hypotonic
      stress. The concurrent activation of BK channels permits K(+) efflux that may
      contribute to regulatory volume decrease.

PMID- 16911251
TI  - Angiotensin II induced contraction of rat and human small intestinal wall
      musculature in vitro.
AB  - BACKGROUND: Angiotensin II (Ang II) is a well-known activator of smooth muscle in
      the vasculature but has been little explored with regard to intestinal wall
      muscular activity. This study investigates pharmacological properties of Ang II
      and expression of its receptors in small-intestinal smooth muscle from rats and
      humans. METHODS: Isometric recordings were performed in vitro on small intestinal
      longitudinal muscle strips. Protein expressions of Ang II typ 1 (AT1R) and typ 2
      (AT2R) receptors were assessed by Western blot. RESULTS: Ang II elicited
      concentration-dependent contractions of rat jejunal and ileal muscle
      preparations. The concentration-response curve (rat ileum, EC(50): 1.5 +/- 0.9 x
      10(-8) M) was shifted to the right by the AT1R receptor antagonist losartan (10(
      7) M) but was unaffected by the AT2R antagonist PD123319 (10(-7) M) as well as by
      the adrenolytic guanethidine (3 x 10(-6) M) and the anticholinergic atropine (10(
      6) M). Human duodenal, jejunal and ileal longitudinal muscle preparations all
      contracted concentration-dependently in response to Ang II. The concentration
      response curve (human jejunum, EC(50): 1.5 +/- 0.8 x 10(-8) M) was shifted to the
      right by losartan (10(-7) M) but was unaffected by PD123319 (10(-7) M). Both AT1R
      and AT2R were detected in all segments of the rat small intestinal wall
      musculature, whereas only AT1R was readily detectable in the human samples.
      CONCLUSION: Ang II elicits contractions of small-intestinal longitudinal muscle
      preparations from the small intestine of rats and man. The pharmacological
      pattern and protein expression analyses indicate mediation via the AT1R.

PMID- 16911252
TI  - Oestrogen status in relation to the early training responses in human thumb
      adductor muscles.
AB  - AIMS: The aims of this study were to identify the mechanisms for the early
      response to training in women of different oestrogen status and to determine
      whether any oestrogen and exercise effects on these would be additive. METHODS:
      We monitored training (ten 5-s contractions per day for 12 weeks)-induced changes
      in the size, strength, voluntary activation capacity and index of crossbridge
      force state (i.e. rapid stretch to isometric torque ratio), in the thumb adductor
      muscles of postmenopausal [eight who had never used, and 14 who were using,
      hormone replacement therapy (HRT)] and seven premenopausal eumenorrhoeic women.
      The contralateral untrained muscle was used as a control. RESULTS: There was a
      significant effect of oestrogen status on the magnitude of training-induced
      strength increment, with the non-HRT postmenopausal group exhibiting the greatest
      benefits (28 +/- 6%, P = 0.024) from training. There were no significant or
      commensurate changes in either cross-sectional area or voluntary activation
      capacity. The index of crossbridge force state improved most in the no-HRT group
      (19 +/- 7%, P < 0.05). CONCLUSIONS: Presence, rather than absence of oestrogen,
      is associated with relatively higher muscle function which limits the potential
      for any further training-induced increments in muscle performance, as would be
      expected if the muscle strengthening actions of training and oestrogen share a
      common, partially saturable physiological pathway. The mechanism that is involved
      in the early training-induced strength increment in the three differing oestrogen
      groups cannot be due to increased size or recruitment. It would appear instead
      that increased motor unit firing frequency is involved.

PMID- 16911253
TI  - Normalized lengthening peak torque is associated with temporal twitch
      characteristics in elderly women but not young women.
AB  - AIM: To determine if greater normalized torque during maximal effort lengthening
      actions in elderly women compared with young women is related to age-associated
      adjustments in neural activation and/or contractile function. METHODS: The right
      knee extensors of 14 young women (21-30 years) and 12 elderly women (65-78 years)
      were assessed for isometric, shortening and lengthening peak torque,
      electromyography (EMG) activity, and isometric twitch contractile properties.
      Knee extensor contractile tissue volume was determined using magnetic resonance
      imaging. RESULTS: Normalized torque was determined as peak torque per unit of
      knee extensor contractile tissue volume. Normalized torque during the isometric
      and shortening actions was similar between age groups (P > 0.05); however,
      lengthening normalized torque was significantly higher for the elderly women (P <
      0.05). In the young women, a significant relationship existed between normalized
      torque and EMG for all muscle actions (P < 0.05), while no association was found
      between normalized torque and temporal twitch characteristics for any muscle
      action (P > 0.05). In the elderly women, a significant relationship existed
      between normalized torque and EMG for the isometric and shortening muscle actions
      (P < 0.05), but not for lengthening normalized torque and EMG (P > 0.05).
      Furthermore, no association existed between isometric and shortening normalized
      torque, and temporal twitch characteristics in the elderly women (P > 0.05);
      however, a significant relationship existed between lengthening normalized
      torque, and the rate of relaxation and contraction duration (P < 0.05).
      CONCLUSIONS: The greater capacity to develop lengthening peak torque relative to
      contractile tissue volume in the elderly women appeared to be associated with age
      related adjustments in the temporal twitch characteristics rather than neural
      activation.

PMID- 16911254
TI  - Chest wall kinematics, respiratory muscle action and dyspnoea during arm vs. leg
      exercise in humans.
AB  - AIM: We hypothesize that different patterns of chest wall (CW) kinematics and
      respiratory muscle coordination contribute to sensation of dyspnoea during
      unsupported arm exercise (UAE) and leg exercise (LE). METHODS: In six volunteer
      healthy subjects, we evaluated the volumes of chest wall (V(cw)) and its
      compartments, the pulmonary apposed rib cage (V(rc,p)), the diaphragm-abdomen
      apposed rib cage (V(rc,a)) and the abdomen (V(ab)), by optoelectronic
      plethysmography. Oesophageal, gastric and trans-diaphragmatic pressures were
      simultaneously measured. Chest wall relaxation line allowed the measure of peak
      rib cage inspiratory muscle, expiratory muscle and abdominal muscle pressures.
      The loop V(rc,p)/V(rc,a) allowed the calculation of rib cage distortion. Dyspnoea
      was assessed by a modified Borg scale. RESULTS: There were some differences and
      similarities between UAE and LE. Unlike LE with UAE: (i) V(cw) and V(rc,p) at end
      inspiration did not increase, whereas a decrease in V(rc,p) contributed to
      decreasing CW end expiratory volume; (ii) pressure production of inspiratory rib
      cage muscles did not significantly increase from quiet breathing. Not unlike LE,
      the diaphragm limited its inspiratory contribution to ventilation with UAE with
      no consistent difference in rib cage distortion between UAE and LE. Finally,
      changes in abdominal muscle pressure, and inspiratory rib cage muscle pressure
      predicted 62% and 41.4% of the variability in Borg score with UAE and LE,
      respectively (P < 0.01). CONCLUSION: Leg exercise and UAE are associated with
      different patterns of CW kinematics, respiratory muscle coordination, and
      production of dyspnoea.

PMID- 16911257
TI  - On labor support and doulas.

PMID- 16911259
TI  - How well will we age? Why we need to consider our health in old age now.

PMID- 16911260
TI  - Emergency contraception: Controversy remains.

PMID- 16911262
TI  - Caring for older women: Nurses face new challenges with this increasingly active
      and vibrant population.

PMID- 16911263
TI  - When lightening strikes: Preparing for maternal cardiac arrest. One hospital's
      journey.

PMID- 16911264
TI  - Conceiving care: How the desires of nursing mothers transformed the delivery of
      our care.

PMID- 16911265
TI  - Understanding gestational trophoblastic disease: How nurses can help those
      dealing with a diagnosis.

PMID- 16911266
TI  - Word power: The effect of literacy on health outcomes.

PMID- 16911267
TI  - Preconception care: Every woman, every time.

PMID- 16911268
TI  - Great leaders are made, not born.

PMID- 16911271
TI  - Reason to connect.

PMID- 16911273
TI  - Erythropoietic protoporphyria advances today, with a special tribute to the late
      Professor Ian Magnus.

PMID- 16911274
TI  - What causes worsening of eczema? A systematic review.
AB  - BACKGROUND: Flares of eczema are attributed to many factors, often with minimal
      scientific evidence. OBJECTIVES: Systematically to search, summarize and
      critically appraise the scientific evidence to support the roles of individual
      'flare factors' in eczema. METHODS: We searched Medline from 1966 until 20 April
      2005 to identify relevant articles for inclusion in this review. No language
      restrictions were imposed. All study designs were included and were ranked
      according to the strength of evidence. Experimental and provocation studies were
      restricted to those using a double-blind design. We included randomized
      controlled trials if they were provocation studies. Meta-analysis was not
      possible due to differences in study populations and methodology. The studies are
      therefore described qualitatively. RESULTS: The roles of foodstuffs (13 studies),
      house dust mite (three), other aeroallergens (two), seasonality (two), bacterial
      infections (one), textiles (three), detergents (one), sunlight (one) and stress
      (two) were assessed in different study populations, using a variety of study
      designs. All studies were performed on selected groups and only four were
      longitudinal in design. Collectively, these studies provide some evidence that
      certain foods, house dust mite, stress and seasonal factors are relevant causes
      of disease worsening in certain subgroups with eczema. No good evidence could be
      found to support the role of detergents, textiles and irritants in causing
      worsening of eczema. CONCLUSIONS: Despite anecdotal lists in textbooks and review
      articles, very little good evidence exists for 'flare factors' in eczema. The
      focus of all of the included studies was on disease worsening rather than
      clinically relevant flares. Studies of longitudinal design are required to
      clarify the roles of these and other putative flare factors in eczema.

PMID- 16911275
TI  - Interferon-gamma-deficient mice are resistant to the development of alopecia
      areata.
AB  - BACKGROUND: Alopecia areata (AA) is a T-cell mediated putative autoimmune disease
      of hair follicles, which can be transferred by CD4(+) T cells. However, whether T
      helper (Th) 1 or Th2 cytokines are predominant has not yet been defined.
      OBJECTIVES: To elucidate the importance of Th1 cells in the pathogenesis of AA we
      investigated the functional role of interferon (IFN)-gamma in the experimental
      induction of AA. METHODS: AA was experimentally induced by grafting full
      thickness skin from AA-affected C3H/HeJ mice on to C3H/HeJ mice with a targeted
      deletion of the Th1 cytokine IFN-gamma gene (IFNgamma(-/-)) and on to wild-type
      mice (IFNgamma(+/+)). RESULTS: While 90% of wild-type mice developed AA, none of
      the IFNgamma(-/-) mice exhibited hair loss. Immunohistochemistry of skin sections
      revealed a dense perifollicular and intrafollicular infiltrate of CD4(+) and
      CD8(+) T cells in controls, while in IFNgamma(-/-) mice skin-infiltrating CD8(+)
      T cells were absent and the number of CD4(+) cells was significantly reduced.
      Aberrant expression of major histocompatibility complex class I and II molecules
      in the putative immune-privileged infrainfundibular site of the hair follicle was
      found to be weaker in AA-resistant IFNgamma(-/-) mice than in control mice with
      AA. Flow cytometry revealed that leucocytes of IFNgamma(-/-) mice did not respond
      to the transfer of AA-affected skin. As distinct from IFNgamma(+/+) mice, neither
      T-cell activation markers nor Th1 cytokines were upregulated in draining lymph
      node cells or skin-infiltrating leucocytes of AA-resistant IFNgamma(-/-) mice.
      However, there was no evidence for a shift towards a Th2 cytokine profile, nor
      for upregulation of regulatory T cells in IFNgamma(-/-) mice. CONCLUSIONS:
      IFNgamma(-/-) mice fail to activate Th1 cells in response to the transplanted
      (auto)antigens, which suggests an essential requirement for IFN-gamma-mediated
      Th1 activation in the induction of AA.

PMID- 16911276
TI  - Spatial expressions of fibronectin and integrins by human and rodent dermal
      fibroblasts.
AB  - BACKGROUND: Human skin shows various morphological characteristics, depending on
      the body site. As these distinct phenotypes have been explained on the basis of
      the variance in epidermal keratinocytes and the presence of skin appendages, the
      spatial distinction of the dermal components has not been fully elucidated.
      OBJECTIVES: To identify and characterize the profiles of mRNAs that are
      abundantly or specifically expressed by fibroblasts derived from trunk skin, but
      not from palmoplantar skin or oral mucosa. METHODS: In order to identify the
      distinct mRNA expression by trunk skin fibroblasts, a subtraction cDNA screening
      was performed first, followed by Northern blotting, Western blotting and
      immunohistochemistry for cultured human and rat dermal fibroblasts and those skin
      tissues. Finally, whole mount in situ hybridization (WISH) was performed to
      examine the differences in the expression of the corresponding gene during the
      developmental stage of mouse embryos. RESULTS: We identified three cDNA clones
      encoding fibronectin (FN), pregnancy-specific beta1-glycoprotein 5 and beta
      actin, respectively, whose mRNAs were abundantly or specifically expressed by
      trunk skin fibroblasts. FN and some integrins were further confirmed to be
      expressed more selectively in human and rat trunk skin fibroblasts, both in terms
      of the RNA and the protein levels, compared with the fibroblasts derived from
      plamoplantar skin and oral mucosa. WISH demonstrated that FN was localized around
      the hair follicles of mouse embryos. CONCLUSIONS: FN, one of most potent
      extracellular matrix molecules, was demonstrated to be spatially transcribed
      depending on the body sites. The distinct expression of FN was suggestive of the
      essential commitment in the process of cutaneous development and morphogenesis of
      appendages originated from hair germ. The paucity of FN in palmoplantar skin and
      oral mucosa might explain the characteristics of these skin phenotypes.

PMID- 16911277
TI  - Pattern of growth and adiposity from infancy to adulthood in atopic dermatitis.
AB  - BACKGROUND: Impaired linear growth has been reported in children with atopic
      dermatitis (AD) but the pattern of growth in height and weight through childhood
      and adolescence has not been described. OBJECTIVES: To define the pattern of
      linear growth and adiposity in AD from early childhood through to adult life.
      PATIENTS AND METHODS: Growth measurements of 70 male and 40 female patients with
      AD followed through childhood and adolescence were studied retrospectively and
      compared with the 1990 U.K. normal values. Height, weight and body mass index
      (BMI) were converted to standard deviation scores (SDS). Regression analysis
      examined whether the mean trend was different from zero. RESULTS: While
      dermatitis was the predominant atopic problem in all 110 patients, 92 had a
      history of asthma which was mild in 85 of 92. Regression analyses showed that the
      trends in height, weight and BMI SDS for AD patients were significantly different
      from zero and also different between males and females. Both sexes were short and
      relatively overweight from early childhood, a trend that was more pronounced in
      males than females. At 5 years (school entry), the 50th centile BMI of male (but
      not female) patients was 0.44 kg m(-2) higher than the reference population but
      height and weight were lower. The age at adiposity rebound in AD males and
      females was 0.8 year and 0.7 year later than the U.K. population (6.2 years vs.
      5.4 years and 6.2 years vs. 5.3 years, respectively). AD patients attained peak
      height velocity later than the 1990 U.K. population (males 16.0 years vs. 13.5
      years, P = 0.0002; females 13.4 years vs. 11.0 years, P = 0.008). In addition,
      males had greater mean gain in height during late adolescence (12.2 vs. 8.8 cm, P
      = 0.03) and were shorter as young adults (170.9 vs. 177.6 cm, P = 0.0005).
      CONCLUSIONS: Our patients with AD were relatively overweight very early but had a
      later adiposity rebound, were short in childhood and had a delayed adolescent
      growth spurt. Serial growth measurements should be done on all children with
      troublesome AD and can be helpful in counselling about the growth prognosis.

PMID- 16911278
TI  - Heterogeneity of fluorescence in psoriasis after application of 5-aminolaevulinic
      acid: an immunohistochemical study.
AB  - BACKGROUND: Psoriasis has been shown to highly accumulate protoporphyrin IX
      (PpIX), but a variable distribution within plaques after fluorescence diagnosis
      is seen. It is unknown what causes this heterogeneity of fluorescence in
      psoriatic skin, despite adequate keratolytic treatment. Variations in
      fluorescence might explain the variable and the mostly partial clinical response
      of psoriasis seen after photodynamic therapy (PDT). OBJECTIVES: This study
      examines morphological and immunohistochemical differences in inhomogeneous PpIX
      induced fluorescence in stable plaque psoriasis. MATERIALS AND METHODS: Fourteen
      patients with stable plaque psoriasis were included in this study. In each
      patient one psoriatic plaque was incubated with 20% 5-aminolaevulinic acid (ALA)
      ointment for 3 h after keratolytic treatment. Fluorescence diagnosis with ALA
      induced porphyrins (FDAP) was performed and subsequently high- and low
      fluorescent psoriatic skin samples were biopsied. Biopsies were investigated with
      respect to histological hyperkeratosis (thickness of stratum corneum),
      proliferation (Ki-67 antigen), keratinization (K10, filaggrin) and inflammation
      (CD3). Digital images acquired with FDAP were analysed using image analysis
      software. RESULTS: Inhomogeneous fluorescence was seen in 12 of the 14 plaques. A
      significantly thicker stratum corneum was found in low-fluorescent psoriatic skin
      compared with highly fluorescent skin. Fluorescence intensity and thickness of
      the stratum corneum proved to be negatively correlated. The variable-fluorescent
      parts of the lesional psoriatic skin showed no differences in epidermal
      proliferation, keratinization or inflammation. CONCLUSIONS: Heterogeneous ALA
      induced fluorescence in psoriasis plaques related to inhomogeneous distribution
      of PpIX in the epidermis may result from differences in penetration of ALA and/or
      light within a plaque caused by differences in stratum corneum thickness. The
      variable clinical response seen after PDT in psoriasis could be explained by
      this. These findings are consistent with the general assumption that optimal
      desquamation prior to FDAP or PDT is required for the most favourable results.

PMID- 16911279
TI  - Correlation with digital dermoscopic images can help dermatopathologists to
      diagnose equivocal skin tumours.
AB  - BACKGROUND: A variety of pigmented skin tumours can lead to diagnostic
      difficulties in dermatopathology. OBJECTIVES: To investigate whether the
      interobserver agreement between histopathological diagnoses of equivocal
      pigmented tumours made by two referral centres can be improved by additional use
      of dermoscopic images. MATERIAL AND METHODS: Retrospective study using 160
      tumours excised in the pigmented skin lesions clinic in Graz and 141 from
      Tubingen. Tumours were diagnosed in the referring centres using clinical data,
      histopathology and, if required, immunohistochemistry. The tumours were initially
      diagnosed as 74 melanomas, 218 melanocytic naevi and nine nonmelanocytic tumours.
      Haematoxylin and eosin sections, patients' age and sex, tumour localization and
      digital dermoscopic images were then exchanged between the participating centres.
      Then, diagnoses were made initially based solely on dermatopathology and clinical
      information. After a washout phase, the same sections were reevaluated with the
      additional use of dermoscopic images. The main outcome measures were the Cohen's
      kappa-coefficients of the initial diagnoses of the centre submitting the cases
      and the diagnoses of the other centre without and with dermoscopy. RESULTS: The
      kappa-coefficient between the initial diagnoses with those made by the second
      centre without dermoscopy was 0.90 in Graz, 0.73 in Tubingen, and 0.81 overall.
      With the additional use of dermoscopy the kappa-value was invariably high with
      0.89 in Graz, and improved to 0.87 in Tubingen, and to 0.88 overall. CONCLUSIONS:
      The additional use of digital dermoscopic images further improved the overall
      very good agreement of histopathological diagnoses between two referral centres.

PMID- 16911280
TI  - Fine-needle aspiration biopsy with ultrasound guidance in patients with malignant
      melanoma and palpable lymph nodes.
AB  - BACKGROUND: Recurrence after treatment of stage I-II melanoma involves regional
      lymph nodes in about 50% of patients. A reliable method is needed to evaluate
      lymph node status (metastatic or not) in the case of palpable lymph nodes.
      OBJECTIVES: To evaluate the efficiency of fine-needle aspiration biopsy (FNAB) in
      examining clinically detected suspicious lymph node in patients followed up after
      surgical removal of stage I-II melanoma. PATIENTS AND METHODS: One hundred and
      twenty FNABs were performed in 67 patients with a suspicious node in an open
      study conducted in a French melanoma regional referral centre, Hopital de l'Hotel
      Dieu. Cytodiagnosis was classified as positive, negative, inadequate or
      inconclusive. Sensitivity, specificity, positive and negative predictive values
      and positive and negative likelihood ratios were calculated after final
      histopathological evaluation. RESULTS: Fifty-eight of 120 FNABs were positive
      (48%), 50 of 120 (42%) were negative, four of 120 (3%) were inconclusive and
      eight of 120 (7%) were inadequate. Among the 108 FNABs in which a definitive
      diagnosis could be given, sensitivity was 98.2% [95% confidence interval (CI)
      90.7-99.9] and specificity was 96.1% (95% CI 86.8-98.9). CONCLUSIONS: FNAB under
      ultrasound guidance is an efficient tool to discriminate better between cases in
      which surgical treatment of the lymph node basin should be performed and patients
      who should return for follow-up. Surgical treatment appears to be required in
      cases of positive FNAB or in inconclusive cases.

PMID- 16911281
TI  - Remembering childhood atopic dermatitis as an adult: factors that influence
      recollection.
AB  - BACKGROUND: Atopic dermatitis (AD) is common in the population, and studies have
      shown that the disease is on the increase. Studies based on hospital records
      reflect selected populations and may miss less severe cases of AD, and the use of
      self-reported questionnaires has the drawback of recall bias. OBJECTIVES: To
      investigate some possible factors influencing recall bias when questionnaires are
      used to establish the prevalence of childhood eczema in an adult population.
      METHODS: A questionnaire regarding past and present eczema was sent to 557 cases
      (with signs suggesting the diagnosis AD) and 554 matched controls (subjects
      lacking signs of AD) born during 1960-1969 and identified in school health
      medical records. Cases and controls were aged 31-42 years at the time of the
      study and 70.5% returned the questionnaire. RESULTS: Of 403 cases, 29% did not
      report childhood eczema in the questionnaire. There was a difference between
      those who did recall their childhood AD (remembering group, RG), and those who
      did not (forgetful group, FG) in who had documented the diagnostic signs in the
      school health records. In the RG the signs were reported by both parents and
      school health personnel in 51% of cases, and in the FG this was true of only 16%.
      The RG had a higher prevalence of eczema after 15 years of age and of hand
      eczema. The RG also reported more visits to physicians after the age of 15 years
      and more time taken as sick leave due to eczema. CONCLUSIONS: Several factors
      influence how well people remember their AD in childhood. These factors include
      disease activity in adult life, disease severity, and who noticed the eczema in
      childhood.

PMID- 16911282
TI  - Acral lentiginous melanoma: a clinicoprognostic study of 126 cases.
AB  - BACKGROUND: Although the histopathological subtype of melanoma has not been
      clearly proven to carry independent prognostic significance, acral lentiginous
      melanoma (ALM) seems to confer a poorer prognosis mainly because disease is often
      more advanced at the time of diagnosis. OBJECTIVES: To investigate the
      distinctive epidemiological and clinical characteristics of ALM, a peculiar
      histological entity, and to identify prognostic factors. METHODS: We performed a
      register-based review of cases from a single large referral centre, the
      University Hospital Department of Dermatology, Lyons, France. We reviewed patient
      demographics, the initial presentation of the lesion, and clinical outcome. ALM
      specific and disease-free survival were estimated using the KaplanMeier method
      and compared using the log-rank test. A Cox model was used to identify prognostic
      factors. RESULTS: One hundred and twenty-six patients were identified as having
      histopathology-proven ALM in our melanoma patient register from 1996 to 2004.
      There were 46 (37%) subungual ALM and 80 (63%) ALM on soles, palms and nonvolar
      sites. The mean age at diagnosis was 63 years. There were 44 (35%) men and 82
      (65%) women, sex ratio M/F 1 : 1.86. The mean Breslow thickness was 2.51 mm
      (range: in situ to 20 mm). There was no evidence of overexposure to ultraviolet
      radiation, nor was there found a predisposing genetic trait. Only 16 (13%)
      patients recalled a history of trauma. Thirty-four ALM (28%) were unpigmented.
      The median ALM-specific and disease-free survival were 13.5 and 10.1 years,
      respectively. The 5-year survival rate was 76%. Multivariate analysis identified
      tumour thickness, male gender and amelanosis as independent clinical prognostic
      factors for both ALM-specific and disease-free survival. CONCLUSIONS: Our study
      provides specific information on the clinical characteristics and outcome of this
      uncommon histological subtype of melanoma. However, the pathogenesis remains
      unknown. Breslow thickness, male gender and amelanosis were significantly
      associated with a poorer prognosis.

PMID- 16911283
TI  - Micro-melanoma detection: a clinical study on 206 consecutive cases of pigmented
      skin lesions with a diameter < or = 3 mm.
AB  - BACKGROUND: Very small pigmented lesions may represent an important diagnostic
      challenge to the clinician. OBJECTIVES: The aim of the present study was to
      establish the diagnostic value, in terms of sensitivity and specificity, of both
      clinical and dermoscopic examinations in a population of patients with unselected
      consecutive pigmented lesions with a maximum clinical diameter of 3 mm. PATIENTS
      AND METHODS: Two hundred and four consecutive patients bearing 206 pigmented skin
      lesions with a maximum diameter of 3 mm were seen and operated on. Twenty-three
      of these lesions were melanomas. Each lesion was subjected to both clinical and
      dermoscopic evaluation before surgery. The results were expressed in terms of
      sensitivity and specificity of both kinds of evaluation. RESULTS: Clinical
      evaluation produced a diagnostic sensitivity of 43% and a specificity of 91%.
      Dermoscopy resulted in a sensitivity of 83% and in a specificity of 69%. The
      comparison between the sensitivity values of the two diagnostic methods showed a
      significant difference (P < 0.01). A high value of significance was also obtained
      comparing the respective specificity values (P < 0.001). CONCLUSIONS: Detection
      of very small melanomas is feasible by accurate visual inspection. Dermoscopy
      appears to be an important aid to diagnosis, provided that physicians are aware
      of this type of lesion and maintain the index of suspicion at a high level.

PMID- 16911284
TI  - Erythropoietic protoporphyria in the U.K.: clinical features and effect on
      quality of life.
AB  - BACKGROUND: Erythropoietic protoporphyria (EPP) is a rare inherited
      photodermatosis that causes lifelong painful photosensitivity. Neither its full
      clinical spectrum nor its impact on quality of life (QoL) has been investigated
      in a large cohort of patients. OBJECTIVES: To document the clinical features of
      EPP and its impact on QoL in a high proportion of all patients with EPP resident
      in the U.K. METHODS: Patients with EPP were identified from U.K. clinical
      databases and assessed by the same clinical investigator over a 7-month period
      using a standardized proforma and validated adult (Dermatology Life Quality
      Index, DLQI) and children's (Children's Dermatology Life Quality Index, CDLQI)
      QoL questionnaires. RESULTS: Three hundred and eighty-nine living patients with
      EPP were identified, of whom 223 [114 females, 109 males; median age 34 years
      (range: 5-87), from 193 families] were investigated. Total erythrocyte porphyrin
      (TEP) was higher in males (median: 25.3 micromol L1) than females (median: 19.3
      micromol L1). The median ages at onset and diagnosis were 1 and 12 years,
      respectively. Median times for onset of symptoms after sun exposure, onset of
      signs (oedema, erythema) and resolution of symptoms were 20 min, 6 h and 3 days,
      respectively. Most patients reported absence of protection by glass (92%),
      priming (85%), exacerbation by wind (68%), no family history of photosensitivity
      (56%), no symptoms during winter (56%) and had chronic skin lesions (79%).
      Symptoms changed little with age but improved during pregnancy in 47% of gravid
      women. Most patients used protective clothing and a sunscreen; 28% were taking
      beta-carotene and a further 56% had taken it; 29% were not under regular medical
      care. Two patients (1%) had liver failure and 8% reported gallstone disease. QoL
      was markedly impaired, with scores similar to those in severe dermatological
      disease (mean DLQI score 14.0, n = 176; mean CDLQI score 12.8, n = 44),
      indicating a large effect on patients' lives. DLQI scores correlated weakly with
      TEP (rs = 0.228; P = 0.002) and time to onset of symptoms (rs = -0.233; P =
      0.002) but not with age at onset. CONCLUSIONS: EPP is a persistent, severely
      painful, socially disabling disease with a marked impact on QoL. Its diagnosis is
      often overlooked. None of TEP, age at onset nor time to onset of symptoms is a
      useful predictor of impaired QoL in individual patients.

PMID- 16911285
TI  - Heat shock protein 105 is overexpressed in squamous cell carcinoma and
      extramammary Paget disease but not in basal cell carcinoma.
AB  - BACKGROUND: Heat shock protein (HSP) 105 is a 105-kDa protein, recently
      discovered by serological analysis of recombinant cDNA expression libraries
      prepared from tumour cells (SEREX), and is still undergoing intensive research.
      SEREX can define strongly immunogenic tumour antigens that elicit both cellular
      and humoral immunity. Previous studies have shown that HSP105 is a cancer testis
      antigen and is overexpressed in various internal malignancies. The expression of
      HSP105 has not been studied in skin cancers. OBJECTIVES: To assess the expression
      of HSP105 in skin cancers including extramammary Paget disease (EMPD), cutaneous
      squamous cell carcinoma (SCC) and basal cell carcinoma (BCC). METHODS: Samples of
      EMPD (n = 25), SCC (n = 23, of which three were metastatic lesions) and BCC (n =
      23) were collected from patients treated in our department between January 2002
      and December 2004. Western blot and immunohistochemical staining methods were
      used to investigate the expression of HSP105. RESULTS: Results of Western blot
      analysis showed overexpression of HSP105 in EMPD and SCC, and minimal expression
      in BCC. Immunohistochemistry results showed that 56% of EMPD, 60% of primary and
      100% of metastatic SCC highly expressed HSP105 while only 13% of BCC lesions
      showed increased staining. CONCLUSIONS: EMPD and SCC overexpress HSP105 while BCC
      does not. Tumours overexpressing HSP105 present ideal candidates for vaccination
      by HSP105-derived peptides or DNA.

PMID- 16911286
TI  - Expression of insulin-like growth factor-1 receptor, p-AKT and p-ERK1/2 protein
      in extramammary Paget's disease.
AB  - BACKGROUND: The insulin-like growth factor-1 (IGF-1) receptor (R)-induced
      phosphatidylinositol 3-kinase (PI3K)/AKT and mitogen-activated protein kinase
      (MAPK)/ERK signal transduction cascade, which have critical roles in prevention
      of apoptosis and regulation of cell cycle progression, plays an important role in
      tumorigenesis. The expression of IGF-1R, AKT and ERK1/2 has been described in
      some human malignancies, but not in extramammary Paget's disease (EMPD).
      OBJECTIVES: To study the expression of IGF-1R, p-AKT and p-ERK1/2 in EMPD and to
      evaluate the relationships among them. METHODS: Thirty-six tissue samples of 34
      patients with primary EMPD were subjected to immunohistochemical staining for IGF
      1R, p-AKT and p-ERK1/2. RESULTS: Of thirty-six EMPD tissue samples, 34, 34 and 28
      were positive for IGF-IR, p-AKT and p-ERK1/2 expression, respectively; 27, 23 and
      17 of the 36 specimens stained positive for IGF-IR, p-AKT and p-ERK1/2 in more
      than half of Paget's cells, respectively. There were significant correlations
      between the IGF-1R and p-AKT expression as well as between IGF-1R and p-ERK1/2
      expression. Taken together, these results indicate that IGF-1R is overexpressed,
      and AKT and ERK1/2 are frequently phosphorylated in EMPD. CONCLUSIONS: Our study
      shows that the expression of IGF-1R and the induction of p-AKT and the p-ERK1/2
      pathway may play an important role in the pathogenesis of EMPD. The IGF-IR system
      might be a potential therapeutic target in EMPD.

PMID- 16911287
TI  - Development and evaluation of an e-learning package for teaching skin
      examination. Action research.
AB  - BACKGROUND: Dermatology is one of many specialities competing for space in the
      undergraduate curriculum, and recent review reveals that in some medical schools
      only a minority of students receives direct teaching from dermatologists.
      Enlargement of medical schools and dispersion of students over multiple sites
      further increase the strain on teaching resources. OBJECTIVES: To develop and
      obtain 'proof of concept' for a technology to teach skin examination, using an
      approach grounded in modern theories of learning. METHODS: The requirements for
      an e-learning technology were identified through literature review and
      qualitative analysis of stakeholders' requirements with respondent and expert
      validation. A method of teaching skin examination was developed by applying
      Anderson's theory of skills acquisition. It was prototyped first on paper, then
      electronically, and its usability as an instructional tool was evaluated.
      RESULTS: The project delivered, firstly, a specification for skin examination
      derived from published evidence, textbook content, and staff and student
      consensus; and secondly, a very useable technology to help students learn skin
      examination (http://www.skillsbase.man.ac.uk). A validation task was completed in
      20 min without significant usability problems, and evaluators found it simple,
      intuitive, interactive and enjoyable to use. Students saw it as an adjunct that
      would help them build confidence and revise for examinations. Nonstakeholder
      teachers expressed concern about the apparent simplicity of its contents and felt
      that it should only be used in association with traditional teaching methods.
      CONCLUSIONS: Students, educationalists and teachers were able to codesign a
      useable skin examination package, which merits evaluation of efficacy. In view of
      the logistic difficulties of teaching dermatology to the growing student
      population, the technology may be a useful adjunct to traditional teaching
      methods. Our approach may inform further developments in educational technology
      in dermatology.

PMID- 16911288
TI  - Ultraviolet A1-induced downregulation of human beta-defensins and interleukin-6
      and interleukin-8 correlates with clinical improvement in localized scleroderma.
AB  - BACKGROUND: In previous studies, distinct immunological abnormalities have been
      reported in localized scleroderma (LS). Several pro-inflammatory cytokines have
      been demonstrated at increased levels in sera of patients with LS in parallel
      with disease activity. Human beta-defensins (hBDs) are peptides with
      antimicrobial activity, but have been also shown to be implicated in tissue
      injury, scarring and wound healing. hBD expression in LS, a condition resembling
      pathological scarring due to excessive stimulation of matrix synthesis and
      fibroblast activation, has so far not been investigated. Ultraviolet (UV) A1
      phototherapy, the most recent advance in the treatment of LS, targets T-cell
      dermal inflammatory infiltrates via induction of various cytokines and soluble
      factors besides well-known effects on collagen metabolism. OBJECTIVES: We sought
      to investigate the effects of UVA1 on the expression and modulation of hBDs and
      several pro-inflammatory cytokines in LS. METHODS: UVA1 phototherapy was
      performed five times weekly for 8 weeks resulting in a total of 40 treatment
      sessions (single dose 20 J cm2, cumulative dose 800 J cm2). hBD-1, hBD-2 and hBD
      3 mRNA as well as tumour necrosis factor-alpha, transforming growth factor-beta,
      interleukin (IL) -2, IL-4, IL-6 and IL-8 mRNA expression were determined by
      quantitative real-time reverse transcription-polymerase chain reaction in
      lesional and unaffected skin of patients with LS. RESULTS: Skin status markedly
      improved in all 14 patients, resulting in a significant reduction of the clinical
      score from baseline to the end of treatment. hBD-1, hBD-2 and hBD-3 mRNA levels
      were higher in lesional skin compared with unaffected skin and skin from healthy
      volunteers. Following UVA1 phototherapy, hBD-1 mRNA decreased in lesional, but
      not in unaffected skin. hBD-3 mRNA levels significantly decreased after UVA1 in
      lesional skin, whereas an increase of hBD-3 was observed in unaffected skin. IL-6
      and IL-8 mRNA levels were significantly elevated in lesional skin and
      significantly decreased after UVA1 irradiation, whereas mRNA for both cytokines
      remained unchanged in irradiated unaffected skin. The decrease of hBD-1, hBD-3,
      IL-6 and IL-8 mRNA paralleled the extent of disease and response to UVA1
      phototherapy. CONCLUSIONS: hBDs and IL-6 and IL-8, cytokines with pivotal
      importance in sclerotic skin diseases, are downregulated by UVA1 in the lesional
      skin of patients with LS. Their pathogenetic relevance with respect to clinical
      improvement needs further investigation.

PMID- 16911289
TI  - Topical methyl aminolaevulinate photodynamic therapy for treatment of facial acne
      vulgaris: results of a randomized, controlled study.
AB  - BACKGROUND: There is a need for alternative treatments for moderate to severe
      acne vulgaris. Preliminary experience suggests that topical methyl
      aminolaevulinate photodynamic therapy (MAL-PDT) may have potential. OBJECTIVES:
      To investigate the efficacy and tolerability of MAL-PDT for treatment of moderate
      inflammatory facial acne. PATIENTS/METHODS: Thirty patients aged 15-28 years with
      moderate to severe acne were included in a blinded, prospective, randomized,
      placebo-controlled multicentre study. Each side of each patient's face was
      randomly assigned to treatment with MAL (160 mg g1) or placebo cream, applied for
      3 h prior to illumination. A second treatment was given 2 weeks later. On each
      occasion, patients assessed the intensity of pain using a 10-cm visual analogue
      scale. Inflammatory and noninflammatory acne lesions were counted at baseline and
      4 and 10 weeks after the last PDT treatment. The investigator assessed the global
      severity of acne at baseline (seven patients had severe acne on at least one side
      of the face) and each study visit using a six-point rating scale. Data were
      analysed on an intention-to-treat basis, including all 30 patients. RESULTS:
      There was a statistically significant greater reduction in the total inflammatory
      lesion count with MAL-PDT compared with placebo PDT at week 12; median reduction
      54% [95% confidence interval (CI) 35-64%] vs. 20% (95% CI 8-50%), P = 0.0006. MAL
      PDT was associated with more pain than placebo PDT, although intensity varied
      across centres and was reduced with repeated treatment. Local adverse events were
      consistent with this treatment modality. CONCLUSIONS: MAL-PDT is effective in the
      treatment of moderate to severe inflammatory facial acne. Further studies are
      warranted to optimize this promising procedure.

PMID- 16911290
TI  - Insect-bite-like Wells' syndrome in association with mantle-zone lymphoma.
AB  - Wells' syndrome is a multifaceted dermatosis with a wide morphological spectrum,
      ranging from characteristic cellulitis-like erythema and wheals to an unusual
      presentation of vesicles and bullae. We describe a patient in whom Wells'
      syndrome presented as an insect-bite-like eruption and was associated with
      underlying mantle-cell lymphoma. We recommend meticulous investigation of
      patients diagnosed with Wells' syndrome manifesting as an insect-bite-like
      eruption.

PMID- 16911291
TI  - Novel treatment of Sezary-like syndrome due to adult T-cell leukaemia/lymphoma
      with daclizumab (humanized anti-interleukin-2 receptor alpha antibody).
AB  - We describe a patient with erythrodermic adult T-cell leukaemia/lymphoma
      resistant to multiple systemic therapies who, on the commencement of daclizumab,
      a humanized anti-interleukin-2 receptor antibody, developed a rapid and sustained
      complete response with resolution of previously debilitating erythroderma,
      suggesting significant activity of this agent in this disease process.

PMID- 16911292
TI  - Koebnerizing sclerodermatous graft-versus-host disease caused by donor lymphocyte
      infusion and interferon-alpha.
AB  - Graft-versus-host disease (GvHD) is a common sequel to allogeneic bone marrow
      transplants, which may be accompanied by desirable graft-versus-tumour effects.
      Sclerodermatous GvHD is a rare subtype that is very difficult to treat. We report
      the first case of sclerodermatous GvHD as part of the Koebner phenomenon. We
      propose that donor lymphocyte infusion and interferon-alpha were involved in the
      pathogenesis of this case.

PMID- 16911293
TI  - L457F missense mutation within the 2B rod domain of keratin 9 in a Japanese
      family with epidermolytic palmoplantar keratoderma.

PMID- 16911294
TI  - Tumoral melanosis as a manifestation of a completely regressed primary melanoma
      with metastases.

PMID- 16911295
TI  - Disseminated dermatophytic pseudomycetomas arising in an immunocompromised
      patient.

PMID- 16911296
TI  - Suberythrodermic pustular psoriasis induced by clopidogrel.

PMID- 16911297
TI  - Recurrence-free survival after sentinel node biopsy in melanoma?

PMID- 16911298
TI  - CD10 is expressed in dermatofibromas.

PMID- 16911299
TI  - A follow-up: previously reported apparent lymphomatoid contact dermatitis, now
      followed by T-cell prolymphocytic leukaemia.

PMID- 16911300
TI  - Urinary retention caused by topical glycopyrrolate for hyperhidrosis.

PMID- 16911301
TI  - Pharmaceutical companies' policies and practices regarding prospective
      registration of dermatology-related clinical trials.

PMID- 16911302
TI  - Thymoma, myasthenia gravis, eruptions of pemphigus vulgaris and a favourable
      course of relapsing melanoma: an immunological puzzle.

PMID- 16911303
TI  - Fasciitis-panniculitis syndrome and advanced gastric adenocarcinoma in
      association with antibodies to single-stranded DNA.

PMID- 16911304
TI  - Fungiform papillary glossitis: a 'new' diagnosis or a 'misdiagnosis'?

PMID- 16911310
TI  - Online hemodiafiltration: back to the future?

PMID- 16911311
TI  - Online hemodiafiltration.
AB  - Online hemodiafiltration (HDF) is an extracorporeal technique for solute removal
      in renal failure, which takes advantage of an enhancement of convective treatment
      by the large amount of ultrapure nonpyrogen dialysate being used for substitution
      of the ultrafiltered volume. It offers many advantages aside from its safe
      inflammatory profile, which is attributable to the use of ultrapure dialysate and
      highly biocompatible dialysis membranes. Due to an improved convective clearance,
      significantly increased removal of large or protein-bound uremic retention
      solutes can be achieved, with a potential benefit on cardiovascular morbidity and
      mortality. Recent observational data indicate that online HDF offers a survival
      advantage even after adjustment for comorbidity and dialysis efficiency. Research
      has been ongoing to maximize further the effectiveness of the technique by new
      technical innovations such as transmembrane-pressure feedback control or mid
      dilution online HDF.

PMID- 16911312
TI  - Scaffold-free, engineered porcine cartilage construct for cartilage defect repair
      -in vitro and in vivo study.
AB  - This study introduces an implantable scaffold-free (SF) cartilage tissue
      construct that is composed of chondrocytes and their self-produced extracellular
      matrix (ECM). Chondrocytes were isolated from the articular cartilages from knees
      of domestic pigs (2-week old) and monolayer-cultured for 3-4 days in Dulbecco's
      modified Eagle's medium supplemented with 10% fetal calf serum and 50 microg/mL
      of ascorbic acid. Briefly treated with 0.25% trypsin-ethylenediaminetetraacetic
      acid (EDTA), an intact chondrocytes/ECM membrane, as a cell sheet was released
      from the plate bottom and subsequently centrifuged into a pellet-type construct.
      Each was grown in vitro for up to 5 weeks and subjected to various assays at
      different time points (1, 7, 14, 21, and 35 days). For in vivo implantation, full
      thickness defects (n = 4) were manually created on the femoro-patellar groove of
      the left porcine knee and 1-week-cultured SF construct was implanted as an
      allograft for a month. One defect (#1) was an empty control and the remaining
      three received different recipes; construct only (#2) or 0.25% trypsin/EDTA
      treated first and then construct and collagen gel (#3) or construct and collagen
      gel (#4). While the total cell numbers significantly increased by 2 weeks and
      then remained stable, cell viability stayed in the mid-70% range through the
      entire culture period. Biochemical assay found continuous glycosaminoglycan (GAG)
      accumulation. Histology exhibited that cell distribution was even in the
      construct and GAG intensity became stronger and uniform with time. Real-time
      reverse transcription polymerase chain reaction (RT-PCR) results showed that
      phenotypic stability peaked at 2 weeks, which was arable to that of freshly
      isolated chondrocytes. Upon analysis of the retrieved implants, some promising
      results were witnessed in the defects (#3) retaining not only their intact mass
      but also chondrocytic morphology with lacuna formation.

PMID- 16911313
TI  - Long-term effects of a multimodal approach including immunoadsorption for the
      treatment of myasthenic crisis.
AB  - A multimodal treatment protocol with immunoadsorption (IA) as the central element
      was used in the treatment of myasthenic crisis (MC). Fifteen patients with MC
      were treated in repeated, uninterrupted 7-day cycles until mobilization with: (i)
      large-volume IA using an antihuman-IgG adsorber, days 1-5; (ii) intravenous
      immunoglobulin substitution (0.3-0.5 g/kg body weight [BW]/day), days 5-7; and
      (iii) immunosuppression with cyclophosphamide (1-2 mg/kg BW/day) and prednisolone
      (0.5-1 mg/kg BW/day), until remission. Patients required a median of 8 days of
      mechanical ventilation, 12 days in the intensive care unit, and 35 days of
      hospitalization. Functional improvement compared to their precrisis condition was
      attained by 14 of 15 patients. MG severity score improved by a mean of 10 points,
      quality of life score by 9.8 points, and Karnofsky index by 29 points in 14 of 15
      patients. Improvements remained stable and no further crises occurred during long
      term follow-up, which averaged 4.4 years. No fatalities due to MC occurred. The
      results demonstrate that our protocol is a potent therapeutic approach in the
      treatment of MC.

PMID- 16911314
TI  - In vitro evaluation of biospecific and pseudobiospecific ligands aimed at
      extracorporeal treatment for immunoglobulin E removal.
AB  - This work investigated the potential use of an alternative adsorbent to anti
      immunoglobulin E (IgE)-agarose for IgE selective adsorption therapy. A screening
      of several commercially available adsorbents (Concanavalin A, Lens culinaris[Lc],
      d-tryptophan, poly-l-lysine, and aminohexyl immobilized on agarose) was done
      through batch system assays, considering some criteria, such as adsorption
      capacity, selectivity, and biocompatibility. In the Lc-agarose adsorbent, total
      IgE, and specific IgE--for the airborne allergens Dermatophagoides pteronyssinus
      and Blomia tropicalis--were significantly better removed (63, 58, and 59%,
      respectively) than immunoglobulin G (19%), immunoglobulin A (33%), immunoglobulin
      M (9%), and albumin (18%). This adsorbent was packed into a column and the effect
      of superficial velocity, ratio of plasma volume to bed volume, number of
      perfusions, and temperature on IgE adsorption were evaluated. In vitro simulation
      of therapeutic adsorption (single perfusion) indicated that about 50% of total
      IgE could be eliminated.

PMID- 16911315
TI  - Preoperative intravenous hydration confers renoprotection in patients with
      chronic kidney disease undergoing cardiac surgery.
AB  - Patients with chronic kidney disease (CKD) are at risk to develop acute renal
      failure (ARF) after open heart surgery. This complication is associated with high
      morbidity, mortality, and cost. Because the ability to concentrate urine is lost
      early in the progression of CKD, renal patients kept on fluid restriction prior
      to surgery may develop severe dehydration, a situation consistently found to be
      one of the most critical risk factors for postoperative ARF. Our goal was to
      investigate whether intravenous hydration for 12 h prior to cardiac surgery could
      prevent acute renal injury in patients with CKD. This is a prospective study in a
      tertiary cardiac surgery center. Forty-five patients admitted for elective open
      heart surgery with moderate-to-severe CKD, as evidenced by a quantified
      glomerular filtration rate less than 45 mL/min, were assigned using a 2/1
      randomization process, to either receive an intravenous infusion of half-isotonic
      saline (1 mL/kg/h) for 12 h before the operation (hydration group, n = 30, 29
      men, 64 + 1.7 years old), or to be simply kept on fluid restriction (control
      group, n = 15, 14 men, 64.2 + 2.8 years old). Groups were not different in
      clinical and intraoperative variables associated with postoperative renal injury.
      ARF developed in 8 of 15 (53%) patients in the control group, but in only 9 of
      the 30 (30%) patients in the hydration group. Four patients in the control group
      (27%), but no one in the hydration group, required dialysis after the operation
      (P < 0.01). Peak creatinine and blood urea nitrogen values were two to three
      times higher in the control group than in the hydration group. Preoperative
      intravenous hydration may ameliorate renal damage in patients with moderate-to
      severe renal insufficiency undergoing cardiac surgery.

PMID- 16911316
TI  - Changes in aortic function after interposition of a tubular graft in the
      descending porcine thoracic aorta.
AB  - The objective of the study was to investigate the alterations of aortic function
      after interposition of a tubular graft in the descending porcine thoracic aorta.
      Eight healthy Landrace pigs were subjected to thoracotomy under sterile
      conditions. A 5-cm-long segment of descending thoracic aorta was replaced with a
      Dacron graft. Pulse wave velocity (PWV) was measured using simultaneous
      recordings of electrocardiogram and Doppler pressure waveforms, which were
      received from right carotid and femoral arteries. Then, the recordings were fed
      to a computer for analytical estimation of PWV in several occasions: right after
      the interposition (D0), and after 15 (D15) and 30 (D30) days time. Euthanasia was
      performed after the D30-recordings and the aortic graft area was removed. "Before
      graft" (BG) as well as "after graft" (AG) aortic regions were examined under
      light microscopy in order to determine the aortic thickness (T) and number of
      lamellar units (LU). Eight sham-operated pigs were used as controls. The results
      showed that PWV decreased as soon as the graft interposition took place and was
      maintained, until the end of experiment (P < 0.05). Aortic wall thickness was
      increased both at pregraft and postgraft areas (P < 0.05), and LUs were also
      increased at the same regions. It is concluded that the interposition of a
      tubular graft in the descending thoracic aorta resulted in a decrease in PWV,
      which may improve left ventricular performance and enhance myocardial perfusion,
      due to a delay in the arrival of the reflecting diastolic wave.

PMID- 16911317
TI  - Organ donation: knowledge, attitudes, and practice in Lagos, Nigeria.
AB  - A cross-sectional study was conducted to determine knowledge and attitudes toward
      organ donation and transplant in Lagos, Nigeria. The study sample was selected
      through a multistaged sampling technique. The survey instrument was a
      standardized self-administered questionnaire. Four hundred and twenty-eight
      subjects participated in the study. The mean age was 31.1 +/- 2.1 years. Two
      hundred and fifty-six (60%) were aware of organ donation. Renal failure was the
      most commonly identified indication for transplant. One hundred and twenty-seven
      (30%) subjects were willing to donate an organ. Knowledge about organ donation
      was significantly higher among those with tertiary level of education (P =
      0.000). Willingness to donate an organ showed a significant relationship with
      younger age (P = 0.002), but not with gender (P = 0.47) or educational status (P
      = 0.09). There is a need to increase awareness about organ donation in Lagos,
      Nigeria.

PMID- 16911318
TI  - Plasma exchange-based plasma recycling dialysis system as a potential platform
      for artificial liver support.
AB  - We developed a plasma recycling dialysis (PRD) system based on plasma exchange
      (PE). In this system, rapid reduction of toxic substances and restitution of
      deficient essential substances are performed by PE, and subsequent blood
      purification is performed by dialysis between separated plasma recycled over a
      purification device and the patient's blood across the membrane of the plasma
      separator. This study was performed to demonstrate the safety and efficacy of
      this system. Hyperbilirubinemia was induced by ligating the bile duct in pigs,
      and 7 days later, only PE for 2 h (group PE) or PE for 2 h followed by PRD for 6
      h (group PE + PRD) was performed. The separated plasma was recycled over anion
      exchange resin through the extra fiber space of the plasma separator. The safety
      and efficacy of this system were evaluated based on the values of hemodynamic and
      laboratory parameters. Transfer from PE to PRD was completed in a few minutes.
      The hemodynamic status and blood cells counts were stable and hemolysis was not
      observed during the procedure. In the PE + PRD group, the concentrations of total
      bile acids continuously decreased (pretreatment, 155.5 +/- 40.6 microM; 2 h [end
      of PE], 76.1 +/- 14.4 microM; 8 h [end of PRD], 25.8 +/- 9.1 microM) and the
      value was significantly lower than in the PE group after 6 h. The total bilirubin
      also continuously decreased during PRD (pretreatment, 55.3 +/- 11.5 microM; 2 h
      [end of PE], 33.8 +/- 8.4 microM; 8 h [end of PRD], 18.6 +/- 7.7 microM) and was
      significantly lower than in the PE group after 4 h. No significant change was
      observed in other laboratory values. This PE-based PRD system allowed a swift
      transfer from PE to sorbent-based blood purification. The safety of this system
      was demonstrated and the removal of toxic substances was significant. This study
      confirmed the clinical utility of this system as a platform for artificial liver
      support.

PMID- 16911319
TI  - Venous leg congestion treated with distal venous drainage during peripheral
      extracorporeal membrane oxygenation.
AB  - Distal venous drainage during extracorporeal membrane oxygenation (ECMO) via
      femoral cannulation is described. It was performed to relieve distal venous
      congestion due to obstruction by the venous cannula. Venous drainage was
      performed with an 11 Fr introducer catheter connected as a T to the main venous
      line. Its effectiveness was confirmed by clinical examination and Doppler
      ultrasound in a patient presenting with acute myocarditis. In addition to distal
      limb perfusion during ECMO, this technique appears safe and simple for adequate
      distal limb drainage, and can be useful in cases where a change of cannulas is
      not possible.

PMID- 16911320
TI  - A reduced priming system.
AB  - Cardiopulmonary bypass (CPB), an integral part of valve surgery, is known to
      cause hemodilution, which can lead to a need for blood transfusion as well as a
      systemic inflammatory reaction. Our aim was to evaluate a reduced priming (RP)
      system for CPB with regard to clinical outcomes in patients undergoing valve
      surgery. Eleven patients were assigned to the new system with an RP volume. The
      RP system allowed for reduced hemodilution and a possible reduction in the
      necessity for blood transfusions.

PMID- 16911321
TI  - In vivo assessment of a rotary left ventricular assist device-induced artificial
      pulse in the proximal and distal aorta.
AB  - The increasing clinical use of rotary left ventricular assist devices (LVADs)
      suggests that chronic attenuation of arterial pulse pressure has no clinically
      significant detrimental effects. However, it remains possible that modulating
      LVAD rotor speed to produce an artificial pulse may be of temporary or occasional
      benefit. We sought to evaluate a pulse produced by a continuous-flow, centrifugal
      pump in an ovine thoracic and abdominal aorta. Both ventricles of an adult sheep
      were resected to eliminate all native cardiac contributions to pulsatility, each
      replaced by a continuous-flow Thoratec HeartMate III blood pump (Burlington, MA,
      USA). An LVAD-induced pulsatile flow was achieved by sharply alternating the
      speed of the magnetically levitated rotor of the left pump between 1,500 rpm
      (artificial diastole) and 5,500 rpm (artificial systole) at a rate of 60 bpm at a
      "systolic" interval of 30%. A catheter was advanced from the ascending aorta to
      the iliac bifurcation via the ventricular assist device outflow graft for
      pressure measurement and data acquisition. The mean LVAD-induced pulse pressures
      were 34, 29, 27, and 26 mm Hg in the ascending, thoracic, and abdominal aorta,
      and the iliac bifurcation, respectively. The maximum rate of pressure rise
      (deltap/deltat) was between 189 and 238 mm Hg/s, approaching that of the native
      pulse, although the energy equivalent pressure did not exceed the mean arterial
      pressure. The HeartMate III's relatively stiff speed control, low rotor mass, and
      robust magnetic rotor suspension result in a responsive system, enabling very
      rapid speed changes that can be used to simulate physiologic pulse pressure and
      deltap/deltat.

PMID- 16911322
TI  - Characterization of an artificial valve flow using the numerical dye washout
      visualization technique: application to the monoleaflet valve with purged flow.
AB  - Until today, no ideal heart valve prosthesis for the replacement of a diseased
      natural valve or for use in ventricular assist devices exists. Valves still cause
      thromboembolic complications originating from thrombus formations in the valve's
      stagnant zones. Optimization of valve design involves avoiding stagnation zones
      and zones of high shear stresses. This requires detailed flow field
      investigations. Usually, the regions which are more prone to thrombus formation
      can be estimated using a dye washout experiment. The method allows an assessment
      of regions with a high or low residence time that may in turn predict regions
      with a corresponding thrombus risk. This successful experimental method was
      simulated using numerical methods with a combination of the computational fluid
      dynamics program FLUENT (Fluent Inc., Lebanon, NH, USA) and of the visualization
      tool AMIRA (TGS Inc., San Diego, CA, USA). The numerical dye washout
      visualization was applied to four monoleaflet valves with varying valve housing
      geometries. The results show a significant difference in the washout processes of
      the examined valves. The dye washout was characterized by a time course of the
      gray value averaged over a defined region of interest. Finally, these curves were
      quantified by a half dye time. The half dye time in the best optimized valve was
      only 0.2753 s. The same time in the original valve was 0.6834 s. This study shows
      that the proposed numerical method of dye washout visualization can be used as an
      additional tool of the flow characterization in artificial organs.

PMID- 16911323
TI  - Reply to editorial entitled: "blood pump technology: a crowded arena," March 2006
      issue.

PMID- 16911324
TI  - Impact of effective valvotomy in mitral stenosis on pulmonary venous flow
      pattern.
AB  - AIMS: Transesophageal Doppler echocardiography (TEE) is a useful tool to
      investigate pulmonary venous flow (PVF) velocity, which is altered in patients
      with mitral stenosis (MS). This study used TEE to analyze the variations in the
      PVF pattern after successful valvar dilatation in MS patients. METHODS/RESULTS: A
      total of 15 MS patients, mean age 27.2 years, underwent effective percutaneous
      balloon valvotomy (PBV). All were submitted to TEE before and after PBV. TEE
      assessed systolic (SPFV) and diastolic (DPFV) peak flow velocities and their
      ratio (SPFV/DPFV), time-velocity integrals (STVI and DTVI) and their ratio, and
      diastolic flow deceleration (DFD). Valvotomy yielded statistically significant
      increases (P < or = 0.05) in the SPFV: increase on average by 67% and STVI by
      120%, as well as in the diastolic component: increased on average by 35%, DTVI by
      33%, and DFD by 75%. CONCLUSION: TEE demonstrated that PBV induced a global
      increase in velocities of PVF, probably related to improvement of left atrial
      emptying.

PMID- 16911325
TI  - The effect of angiotensin II type-1 receptor gene polymorphisms on doppler blood
      flow parameters of carotid and brachial arteries in patients with myocardial
      infarction.
AB  - BACKGROUND: Genetic influence on Doppler blood flow parameters of carotid and
      brachial arteries (BA) is uncertain. We investigated the relationship between the
      angiotensin II type-1 receptor (AT1R) gene polymorphism and the blood flow
      characteristics of common carotid arteries (CCA) and BA by color Doppler
      ultrasound (CDUS) in patients with a first anterior acute myocardial infarction
      (AMI). METHODS AND RESULTS: Sixty-seven patients (15 women and 52 men), aged 25
      77 years, with anterior AMI were studied. The AT1R genotypes were established.
      Based on the polymorphism of the AT1R, they were classified into three groups:
      AT1R AA genotype (Group1, n = 42 patients), AT1R AC genotype (Group 2, n = 17
      patients), and AT1R CC genotype (Group 3, n = 8 patients). Peak-systolic velocity
      (PSV) and end-diastolic velocity (EDV) of right and left CCA, PSV of right BA,
      and intimal-medial thickness (IMT) of both CCA were measured by CDUS. All results
      evaluated statistically. The AT1R genotypes were distributed as follows: 63% AA,
      25% AC, and 12% CC. PSV of BA and both CCA were higher in patients with CC and AC
      than AA (P < 0.05). Also, IMT of both CCA were also higher in the same groups (P
      < 0.05). CONCLUSIONS: Our results suggest that AT1R gene polymorphism influences
      Doppler blood flow parameters of both BA and CCA, and IMT of CCA. Although
      further studies are required.

PMID- 16911326
TI  - Preload independence of isovolumic relaxation flow propagation velocity.
AB  - To evaluate whether isovolumic relaxation flow propagation velocity (IRFPV) is
      independent of preload alterations, 41 healthy subjects (35 +/- 7 years) were
      included for Doppler examinations at three different positions, i.e., supine,
      Trendelenburg, and reverse Trendelenburg. A positional difference was detected in
      the peak velocity of the transmitral early diastolic flow wave (P = 0.012) and
      the peak velocities of both early (P = 0.004) and late (P = 0.007) diastolic
      mitral annular velocity waves. In contrast, there was no positional difference in
      the early diastolic inflow propagation velocity or IRFPV. In conclusion, IRFPV is
      a preload-independent Doppler parameter.

PMID- 16911327
TI  - Mitral annular systolic velocity reflects the left atrial appendage function in
      mitral stenosis.
AB  - BACKGROUND: Left atrial appendage (LAA) dysfunction is an independent predictor
      of thromboembolism in mitral stenosis (MS). OBJECTIVES: To investigate whether
      there is a relation between annular velocities obtained by tissue Doppler imaging
      and LAA function and to determine if the annular velocities can predict the
      presence of the inactive LAA in MS. METHODS: Eighty-five MS patients and 80
      healthy controls were evaluated by transthoracic echocardiography and all
      patients underwent transesophageal echocardiography. The annular systolic (S
      wave) and diastolic (E- and A-waves) velocities were recorded. Inactive LAA was
      defined as LAA emptying velocity <25 cm/sec. Patients were divided into three
      groups; group I (n = 43): sinus rhythm (SR) and LAA emptying velocity > or =25
      cm/sec, group II (n = 15): SR and LAA emptying velocity <25 cm/sec and group III
      (n = 27): atrial fibrillation. RESULTS: Thrombus was detected in 12 patients and
      spontaneous echo contrast (SEC) was detected in 48 patients. Both S-wave and peak
      LAA emptying velocities were decreasing, while SEC frequency and density were
      increasing from group I to group III. There was a positive correlation between
      LAA emptying and S-wave velocities (P < 0.001, r = 0.682). Multivariate
      regression analysis showed that only S-wave is the independent predictor of
      inactive LAA (P = 0.001, odds ratio = 0.143, 95% CI = 0.047-0.434). In patients
      with SR, the cutoff value of S-wave was 13.5 cm/sec for the prediction of the
      presence of inactive LAA (sensitivity: 95.3%, specificity: 93.3%). CONCLUSIONS: S
      wave is an independent predictor of inactive LAA and a useful parameter in
      estimating inactive LAA in MS with SR.

PMID- 16911328
TI  - Feasibility and clinical impact of live three-dimensional echocardiography in the
      management of congenital heart disease.
AB  - BACKGROUND: Precise assessment of congenital heart lesions requires inferential
      evaluation from multiple two-dimensional echocardiographic images (2DE). The aim
      of our study was to assess the usefulness of transthoracic live three-dimensional
      echocardiography (3DE) in the evaluation of congenital heart disease. METHODS:
      Eighty-two patients (from 4 months to 31 years, mean age 12 +/- 7.5, 38 males and
      44 females), known to have congenital heart lesions, prospectively underwent both
      2DE and 3DE. Conventional data acquisition by 2DE and "full volume" 3DE
      acquisition (apical four chambers, parasternal long and short axes, subcostal
      windows) were carried out by two independent and blinded operators. Data derived
      from 3DE were compared to 2DE, and 3DE results were graded into three categories:
      (A) new findings not seen on 2D echo studies, but not critical to therapeutic
      decision making; (B) additional anatomic information useful in therapeutic
      decision making; and (C) information equivalent to 2D echo studies. RESULTS: Two
      out of 82 patients (2%) were excluded because of suboptimal 3DE images. In
      comparison with 2DE studies, 3DE was graded A in 23 patients (29%), B in 28
      patients (35%), and C in 29 patients (36%). In the patients with group B results,
      atrial and ventricular septal defects, endocardial cushion defects, and l
      transposition of great vessels were the most represented pathologies in which 3DE
      aided medical or surgical therapeutic options. While the new findings in group A
      did not influence therapy, they defined the whole spectrum of abnormalities in
      those patients. In patients who fell under group C results, 3DE provided a direct
      realistic display of the pathology detected by 2DE. CONCLUSIONS: Our study
      demonstrates that live 3DE, easily performed at the bedside, provides incremental
      information on patients with a variety of congenital heart lesions. In the
      clinical scenario, it clarifies the pathology in all its dimensions, particularly
      in complex lesions with the incremental information having impact on therapeutic
      decision making.

PMID- 16911329
TI  - Real time three-dimensional echocardiography in assessing ventricular septal
      defects: an echocardiographic-surgical correlative study.
AB  - BACKGROUND: Two-dimensional echocardiography (2DE) enhanced by combining with
      color Doppler technology has significant limitations in providing precise
      quantitative information, geometric assumptions to calculate chamber volume,
      mass, and ejection fraction. Reconstructed three-dimensional echocardiographic
      (3DE) systems (from multiple cross-sectional echocardiographic scans) are still
      cumbersome and time-consuming. Real time 3DE (RT-3DE) with shorter imaging time
      than with 3D reconstruction techniques can obtain qualitative and quantitative
      information on heart disorders. Our purpose was to investigate the feasibility
      and potential value of RT-3DE as a means of accurately and quantitatively
      estimating the size of VSD to correlate with the surgical findings. MATERIALS AND
      METHODS: 38 patients with VSD were examined with RT-3DE. 3D image database was
      postprocessed using TomTec echo 3D workstation. The results were compared with
      the results measured by 2 DE and surgical findings. RT-3DE produced novel views
      of VSD and improved quantification of the size of the defect. The sizes obtained
      from 3DE have equivalent correlation with surgical findings as diameter measured
      by 2DE (r = 0.89 vs r = 0.90). Good agreement between blinded observers was
      achieved by little interobserver variability. CONCLUSION: RT-3DE offers
      intraoperative visualization of VSD to generate a "virtual sense of depth"
      without extending examining time. From an LV en face projection, the positions,
      sizes, and shapes of VSDs can be accurately determined to permit quantitative
      recording of VSD dynamics. It is a potentially valuable clinical tool to provide
      precise imaging for surgical and catheter-based closure of difficult
      perimembranous and singular or multiple muscular VSD.

PMID- 16911330
TI  - Aortic valvular regurgitation: prevalence and clinical characteristics in a
      predominantly obese adult population not taking anorexigens.
AB  - BACKGROUND: We recently reported the prevalence of aortic regurgitation (AR) by
      Doppler echocardiography (echo) in obese subjects to be higher than in some
      previous reports. OBJECTIVE: To describe the prevalence of AR in an obese
      population not taking anorexigens as a function of demographic characteristics,
      cardiovascular risk factors, and other potential predictors. METHODS: In 539
      adult subjects, cardiovascular status was evaluated by medical history, physical
      examination, and Doppler echocardiograms performed according to a standardized
      imaging protocol. Echocardiographic readers were blinded as to each subject's
      medical and medication histories. Associations of AR with demographic and
      comorbid factors were examined. RESULTS: Subjects had a mean (+/- SD) body mass
      index (BMI) of 35 +/- 7 kg/m2, and were predominantly white (87.6%), females
      (74%), with a mean age of 47 +/- 12 years. AR by Food and Drug Administration
      criteria (> or =mild) was present in 4.1% of the subjects. Covariates
      significantly associated with AR were increasing age (P < 0.001), presence of a
      history of hypertension (P = 0.001), left ventricular (LV) internal dimensions (P
      < 0.005), and tricuspid and mitral regurgitation grade (P < 0.001). CONCLUSIONS:
      Clinical and Doppler echo evaluation of a large, predominantly obese, adult
      population revealed that AR was more prevalent than in some previous reports and
      was highly correlated with increased age, presence of a history of hypertension,
      LV internal dimensions, tricuspid and mitral regurgitation.

PMID- 16911331
TI  - Impaired endothelial function in patients with myocardial bridge.
AB  - OBJECTIVE: The relationship between myocardial bridging (MB) and ischemic heart
      disease is still controversial. In this study, we aimed to evaluate the existing
      atherosclerosis and noninvasive endothelial function of brachial artery in
      patients with MB. METHODS: The present study included 50 patients (group I) who
      had MB in left anterior descending (LAD) on coronary angiography. All of the
      coronary artery segments were evaluated by intravascular ultrasound (IVUS).
      Endothelial function was assessed with measurement of flow-mediated dilatation
      (FMD) and nitrate-dependent dilatation in the brachial artery. The study also
      included 30 healthy control subjects (group II). Patients in the group I were
      further subdivided into two subgroups based on the findings on IVUS: group IA
      included 20 patients without atherosclerotic lesions and group IB included 30
      patients with atherosclerotic coronary artery disease in addition to MB. RESULTS:
      FMD values were found to be significantly lower in the patients with MB (group I)
      than in the control (6.4 +/- 3% vs 11 +/- 4%, P <0.001). In regard to FMD values
      in subgroups, FMD was 7 +/- 2% in the group IA and 5.8 +/- 1% in the group IB (P
      = 0.023). On IVUS, atherosclerotic plaque was found proximal to the bridge in the
      same coronary artery segment in addition to MB in 75% of the patients in group I
      (group IB). No atherosclerotic plaque was found in within or distal segments of
      MB. CONCLUSION: Endothelial function is impaired in patients with MB and there is
      an increased tendency for atherosclerosis proximal to the bridge in the patients
      with MB. Endothelial dysfunction is more severe in the patients with
      atherosclerosis proximal to the bridge.

PMID- 16911332
TI  - Transient left ventricular "hypertrophy" in a woman with meningoencephalitis.
AB  - We report the echocardiographic findings in a 27-year-old woman with viral
      meningoencephalitis and a positive test for cardiac troponin. Initially, the
      basal parts of the left ventricle were severely hypokinetic, whereas contraction
      in the mid-ventricle and apex was normal. A second echocardiogram obtained 19
      days after the development of pulmonary edema showed a generalized, severe
      myocardial thickening, the left ventricular ejection fraction being normal. Three
      months after the initial examination the "hypertrophy" had disappeared. The
      serial echocardiograms along with a positive cardiac troponin led to the
      diagnosis of myocarditis, which can very rarely present with the
      echocardiographic picture of severe left ventricular thickening.

PMID- 16911333
TI  - Atrial dissection-like appearance caused by ileus due to metastatic renal cell
      carcinoma.
AB  - Atrial dissection is an uncommon entity, defined as a gap from the mitral or
      tricuspid annular area to the interatrial septum or atrial wall, creating a new
      chamber with or without communication into the true left or right atrium. We
      present the interesting images of an atrial dissection-like appearance in the
      right atrium, which was actually caused by an ileus due to metastatic renal cell
      carcinoma in a 82-year-old man. The causes of true atrial dissection were also
      briefly discussed.

PMID- 16911334
TI  - Fibrosing TB mediastinitis presenting as a superior vena cava syndrome: a case
      presentation and echocardiogram correlate.
AB  - A 49-year-old woman developed a chronic obstruction of the superior vena cava
      (SVC) as a complication of mediastinal tuberculosis. Echocardiography findings
      are presented along with the cavography. Symptoms disappeared after stenting the
      fibrosed SVC. Transesophageal echocardiogram findings led to the condition's
      final resolution.

PMID- 16911335
TI  - Recurrent strokes in a young patient with papillary fibroelastoma: a case report
      and literature review.
AB  - Since the introduction of echocardiography the diagnosis of papillary
      fibroelastomas (PFEs) in living patients has increased. They are second most
      common after myxomas representing 10% of cardiac tumors. The present case is of a
      patient with recurrent cerebrovascular accidents and documented protein S
      deficiency who continued to stroke despite adequate anticoagulation. Mitral valve
      PFE was suspected on echocardiography and confirmed at surgical excision. Two
      large studies published in the last decade describe the echocardiographic and
      clinical characteristics of PFEs which although are histologically benign, may
      present with a clinical course of devastating consequences owing to its strategic
      location within the cardiac structures. Echocardiography, particularly
      transesophageal echocardiography (TEE), provides the necessary anatomical
      resolution and detail to ascertain location, extent of involvement, and
      hemodynamic implications. Tissue diagnosis is based on characteristic
      histopathological features of avascular fronds lined by endothelial cells,
      containing varying amounts of elastin. The echocardiographic characteristics
      along with treatment options are reviewed.

PMID- 16911336
TI  - Noncatheter-associated vegetative phlebitis of the superior vena cava presenting
      with multiple lung abscesses.
AB  - We present a patient with a large vegetation in the superior vena cava (SVC)
      presenting with multiple staphylococcal lung abscesses. We believe that this is
      the first reported case of vegetative phlebitis of the SVC without a history of
      central venous catheter line. Our case emphasizes the need for careful imaging
      SVC using transesophageal echocardiography in bacteremic patients even in the
      absence of a central catheter.

PMID- 16911337
TI  - Usefulness of live/real time three-dimensional transthoracic echocardiography in
      the assessment of atrioventricular septal defects.
AB  - We studied nine patients (five newborns and infants, two children, and two
      adults) with atrioventricular septal defects (four complete, one intermediate,
      and four partial) utilizing live/real time three-dimensional transthoracic
      echocardiography (3DTTE) and a 4-MHz matrix array transducer. In all patients,
      3DTTE provided additional morphological and/or functional information as compared
      to standard two-dimensional transthoracic echocardiography (2DTTE). 3DTTE may be
      a useful supplement to 2DTTE in the assessment of atrioventricular septal
      defects.

PMID- 16911338
TI  - Imaging of diastolic mitral regurgitation in a patient with acute type a aortic
      dissection with diastolic prolapse of intimal flap into left ventricle.

PMID- 16911339
TI  - Giant coronary artery fistula with aneurysm and multiple openings: a two
      dimensional echocardiographic evaluation.

PMID- 16911340
TI  - Three-dimensional echocardiographic evaluation of an aspergilloma complicating
      right ventricular permanent pacemaker implant.

PMID- 16911341
TI  - Protocol for optimal detection and exclusion of a patent foramen ovale using
      transthoracic echocardiography with agitated saline microbubbles.
AB  - Agitated saline bubble studies in conjunction with echocardiography, in
      particular transesophageal echocardiography, are currently the principal means in
      the diagnosis of patent foramen ovale (PFO). We describe techniques and
      guidelines for the detection and exclusion of a PFO. The potential for
      misinterpretation of these bubble studies exists and therefore, several false
      positive and false negative scenarios are illustrated and discussed.

PMID- 16911342
TI  - Gamma-hydroxybutyrate--a drug of abuse.
AB  - Gamma-hydroxybutyrate (GHB) is a drug of abuse that causes euphoria, anxiolysis,
      and hypnosis. The recent rise in the recreational intake of GHB, as well as its
      association with 'drug rape', has turned the attention to GHB in acute hospital
      settings. Acutely admitted GHB intoxicated patients may display various levels of
      sedation or coma, but may also show paradoxical agitation, combativeness, or self
      injurious behaviors. The symptoms can be nonspecific and the definite diagnosis
      therefore normally relies on the detection of GHB in blood or body fluids, which
      is an analysis that may not be promptly available. As a basis for understanding
      the clinical features of GHB intoxication and abuse, we here review the
      pharmacological and neurophysiological knowledge about GHB, which stems from
      decades of clinical and basic GHB research. In addition, we discuss the latest
      discoveries in the quest for distinct GHB receptors in the brain, and their
      possible implications for future therapies of GHB abuse.

PMID- 16911343
TI  - Comparison of the efficacy and tolerability of new antiepileptic drugs: what can
      we learn from long-term studies?
AB  - OBJECTIVE: A review of long-term open-label studies was performed with the aim of
      detecting differences in efficacy and/or tolerability of new antiepileptic drugs
      (AEDs). METHODS: From more than 500 open studies conducted to evaluate the
      efficacy and tolerability of gabapentin (GBP), lamotrigine (LTG), levetiracetam
      (LEV), oxcarbazepine (OXC), pregabalin (PGB), tiagabine (TGB), topiramate (TPM)
      or zonisamide (ZNS), we selected all studies that reported or allowed us to
      calculate the number of patients who achieved seizure freedom for 6 months and/or
      the number of patients withdrawing for adverse effects and/or the number or
      percentage of patients continuing treatment after 1 year. RESULTS: No studies
      were found in which this information was available for OXC, PGB, TGB or ZNS. The
      number of patients who achieved seizure freedom for 6 months was reported in four
      studies each for GBP and TPM, five studies for LTG, and eight studies for LEV.
      The best efficacy profile using this end point was found for LEV, followed by
      TPM, LTG, and GBP. Twenty-two studies reported the number of patients withdrawing
      due to adverse effects. LEV was the best-tolerated AED, a little ahead of LTG,
      and significantly better than GBP or TPM . TPM was by far the least well
      tolerated drug. Information concerning patients continuing treatment after 1 year
      was reported in two GBP studies, two TPM studies, six LEV studies and five LTG
      studies. GBP had a very low retention rate (between 20% and 25% of patients
      continued the drug), while TPM and LTG had a retention rate of 40-60% and LEV had
      a retention rate of 60-75%. CONCLUSION: One limitation of these rankings is that
      their statistical value is limited because of the indirect nature of the
      comparisons. Anyhow, this review covers the main studies published thus far on
      this subject and provides full updated information on the current literature
      about these drugs.

PMID- 16911344
TI  - Levetiracetam: a long-term follow-up study of efficacy and safety.
AB  - OBJECTIVES: To evaluate the efficacy and safety of long-term add-on treatment
      with levetiracetam 1,000-4,000 mg/day. PATIENTS AND METHODS: In this multicenter,
      open-label follow-up study, 505 patients, from 10 European countries, who had
      benefited from previous add-on treatment with levetiracetam in a clinical trial
      or compassionate-use program were enrolled; 274 (54.3%) stayed to the end. Most
      then continued levetiracetam by prescription or in a named patient program, where
      it was not yet commercially available. Mean treatment duration was 1,045 days
      (range: 24 days to >7 years). Median daily dosage was 3,000 mg/day (range: 250
      6,000 mg/day), with 250 (49.5%) patients receiving levetiracetam for >3 years.
      RESULTS: Median total and partial seizure frequency per week over the evaluation
      period were 0.8 and 0.7; seizure frequency per week was generally stable over
      time and remained low. There was a probability of 6.6% of remaining seizure-free
      for the first 3 years, and of 18.9% of having a seizure-free period of at least 3
      years at any time. Most adverse events were mild or moderate and unrelated to
      study drug. Levetiracetam was well tolerated, and provided stable seizure control
      during long-term treatment.

PMID- 16911345
TI  - A randomized, placebo-controlled study of oxcarbazepine in painful diabetic
      neuropathy.
AB  - OBJECTIVES: To evaluate the efficacy and safety of oxcarbazepine (1200 mg/day) in
      patients with painful diabetic neuropathy in a multicentre, double-blind, placebo
      controlled, 16-week study. METHODS: A total of 141 patients were randomized to
      oxcarbazepine (1200 mg/day) (n = 71) or placebo (n = 70). The primary efficacy
      variable was the change in mean visual analogue scale (VAS) score from baseline
      to the last week the patient participated in the study. RESULTS: The reduction in
      mean VAS score from baseline to the last study week was similar between the
      oxcarbazepine and placebo groups. The majority of adverse events (most of which
      first occurred during titration) were mild to moderate in severity and resolved
      over the course of the study. CONCLUSIONS: In this study, no statistically
      significant difference in therapeutic effect was observed between oxcarbazepine
      (1200 mg/day) and placebo. However, further studies are necessary to assess the
      effective dose range of oxcarbazepine in the treatment of painful diabetic
      neuropathy.

PMID- 16911346
TI  - Patient satisfaction with switching to Stalevo: an open-label evaluation in PD
      patients experiencing wearing-off (Simcom Study).
AB  - OBJECTIVES AND METHODS: This study investigated the ease with which 52
      Parkinson's disease patients already receiving adjunct entacapone to traditional
      levodopa were switched to Stalevo (levodopa/carbidopa/entacapone). RESULTS: The
      switch to Stalevo was straightforward for most patients taking standard-release
      levodopa with 86% of these patients being able to replace their entire regimen
      without having to change the amount of levodopa taken. The majority of patients
      (54%, P = 0.162) preferred Stalevo; 31% preferred their prior treatment regimen;
      15% had no preference. Patients found Stalevo more simple to dose (94%), more
      convenient to use (84%), easier to handle (84%), easier to remember (67%) and
      easier to swallow (59%), compared with their previous medication. CONCLUSIONS:
      Stalevo was well tolerated, with a low incidence of adverse events. The study
      shows that Stalevo is an effective, preferred and well-tolerated means of
      delivering levodopa/carbidopa/entacapone in one easy-to-use tablet.

PMID- 16911347
TI  - Determinants of early outcome in spontaneous lobar cerebral hemorrhage.
AB  - OBJECTIVE: To identify determinants of early outcome in spontaneous lobar
      hemorrhage. MATERIALS AND METHODS: From 2500 acute stroke patients included in a
      prospective hospital-based stroke registry over a 12-year period, 97 cases of
      lobar hematoma were selected. Determinants of in-hospital mortality were studied
      in multiple regression models. RESULTS: Lobar hematomas accounted for 3.9% of all
      acute stroke patients and 35.9% of intracerebral hemorrhages. The presence of
      chronic obstructive pulmonary disease (COPD) was a significant predictive
      variable in the model based on demographic variables and vascular risk factors
      [odds ratio (OR): 17.18; 95% CI: 1.77-166.22] and in the model based on these
      variables plus clinical data (OR: 15.12; 95% CI: 1.27-179.59). Other predictive
      variables included altered consciousness, previous cerebral infarct and chronic
      liver disease. CONCLUSIONS: COPD appeared as the most important predictor of
      death during hospitalization after lobar cerebral hemorrhage, a finding not
      generally acknowledged earlier.

PMID- 16911348
TI  - Perfusion and diffusion magnetic resonance imaging in idiopathic intracranial
      hypertension.
AB  - OBJECTIVES: Idiopathic intracranial hypertension (IIH) is characterized by
      abnormal elevation of intracranial pressure without any underlying etiologic
      factor. Papilledema is the major clinical finding whereas neuroradiological
      imaging findings are almost always normal. The aim of this preliminary study was
      to determine if diffusion and perfusion magnetic resonance imaging in patients
      with IIH might be beneficial in the management of the disease. MATERIALS AND
      METHODS: Prospectively, we evaluated standard magnetic resonance, magnetic
      resonance angiographies and venographies, diffusion and perfusion magnetic
      resonance findings of 16 patients with IIH and of 16 age-, sex-, and weight
      matched normal individuals as a control group. Patients with IIH underwent a
      detailed neuroophthalmologic examination and lumbar puncture for evaluation of
      cerebrospinal fluid pressure. Magnetic resonance imaging was performed with 1.5 T
      equipment. RESULTS: On physical examination, all patients had characteristic
      papilledema, varying degrees of headache, blurred vision and tinnitus.
      Cerebrospinal fluid pressure was higher than 250 mm H2O in all patients. A
      statistically significant decrease in cerebral blood flow in six patients,
      whereas insignificant increase in two were detected. Cerebral blood volume values
      were almost similar to normal control group's values. Significant mean transit
      time prolongation was found in six patients as well. CONCLUSIONS: Idiopathic
      intracranial hypertension is a clinical syndrome which requires prompt diagnosis
      and a thorough evaluation. Treatment is crucial for preventing visual loss and
      improving associated symptoms. It is also important to detect cerebral perfusion
      changes, as cerebrovascular complications may be associated. Although our patient
      group is small for statistical evaluation, it is a preliminary study using
      perfusion and diffusion magnetic resonance which may contribute to IIH
      management.

PMID- 16911349
TI  - Health-related quality of life in narcolepsy.
AB  - OBJECTIVES: To describe health-related quality of life in Norwegian patients with
      narcolepsy compared with data from the general population. PATIENTS AND METHODS:
      Seventy-seven patients with narcolepsy with cataplexy were included in the final
      analysis. Health-related quality of life was assessed by SF-36 questionnaire.
      RESULTS: Men and women with narcolepsy had lower scores in all SF-36 domains,
      except vitality. Most profoundly affected were bodily pain (men: p = 0.0001,
      women: p = 0.0001), social function (men: p = 0.0001, women: p = 0.0001) and
      general health (men p = 0.04, women: p = 0.0001). CONCLUSIONS: Narcolepsy has a
      clear negative effect on quality of life which is not sufficiently counteracted
      by medical treatment. We suggest that earlier diagnosis and treatment after onset
      of symptoms may be important in reducing the negative effects on quality of life.
      Special attention should be paid to the patients social functioning and general
      well-being.

PMID- 16911350
TI  - Cerebrospinal fluid Flt3 ligand level in patients with amyotrophic lateral
      sclerosis.
AB  - OBJECTIVES: The Flt3 ligand (FL) is a cytokine with a neurotrophic and
      antiapoptotic activity in the central nervous system that induces the survival of
      neurons. The aim of the study was to measure levels of FL in amyotrophic lateral
      sclerosis (ALS) patients. MATERIALS AND METHODS: The study involved 23 ALS
      patients and 23 people in the control group. The measurement of FL in the
      cerebrospinal fluid (CSF) and serum was performed by the enzyme-linked
      immunosorbent method. RESULTS: Results showed that CSF FL levels were
      significantly increased in ALS patients compared with the controls (P < 0.05) but
      the serum levels of this cytokine did not differ from the controls (P > 0.05).
      There was no significant correlation between CSF and serum FL levels and clinical
      parameters of ALS (P > 0.05). The difference in CSF/serum ratio of FL between ALS
      patients and controls was not statistically significant (P > 0.05). CONCLUSION:
      An increase in CSF FL levels in ALS patients, observed in this study, could be a
      compensative response for neurodegeneration but may also reflect increased
      diffusion of this cytokine into the central nervous system caused by blood-CSF
      barrier dysfunction.

PMID- 16911351
TI  - Clinical characterization and evaluation of DYT1 gene in Indian primary dystonia
      patients.
AB  - OBJECTIVES: Dystonia is a common movement disorder. The purpose of this study is
      to examine the relative distribution of the primary dystonia subtypes and
      identify mutation (s) in the DYT1 gene in Indian patients. MATERIALS AND METHODS:
      Primary dystonia patients (n = 178) and controls (n = 63), lacking any symptoms
      of the disease, were recruited for the study from eastern India. The nucleotide
      variants in the DYT1 gene were identified by carrying out polymerase chain
      reaction, single stranded conformation polymorphism, and DNA sequencing. RESULTS:
      Unlike other reports, pain and/or tremor was more common in our sporadic patients
      than in familial cases. Three reported and two novel changes were identified in
      this gene. The homozygous genotype (G,G) for a missense variant (c.646G > C;
      Asp216His) was significantly over-represented in the patients compared with
      controls (P < 0.05). However, the commonly reported 3 bp deletion (904-906delGAG)
      was not detected. CONCLUSION: Our results suggest that the DYT1 gene might have a
      limited role in causation of dystonia in the Indian population.

PMID- 16911352
TI  - Stress and immune regulation.

PMID- 16911353
TI  - Pathophysiology of nasal obstruction and meta-analysis of early and late effects
      of levocetirizine.
AB  - Nasal obstruction, also referred to as congestion, blockage or stuffiness, is a
      crucial symptom in allergic rhinitis (AR) and may affect sleep as well as quality
      of life. Early- and late-phase-allergic reactions both contribute to nasal
      obstruction, although it primarily represents a major symptom in the chronic
      allergic reaction. A complex network of inflammatory and neurogenic phenomena
      relates to chronic nasal obstruction, including the subepithelial accumulation of
      inflammatory cells, particularly mast cells and eosinophils, and the release of
      neuropeptides. Nasal obstruction is a difficult-to-treat symptom.
      Vasoconstrictors (decongestants) and intranasal corticosteroids, due to their
      anti-inflammatory properties, have mainly been used for relieving the nasal
      passages from the congested mucosa. However, there is accumulating evidence
      recently that the latest-generation potent antihistamines have decongestant
      properties in AR. This paper aims to review the pathophysiologic background of
      nasal obstruction and the evidence for an antihistamine, levocetirizine, in
      relieving nasal congestion. A meta-analysis on the early and late effects of
      levocetirizine on nasal obstruction under artificial and natural allergen
      exposure conditions is presented, demonstrating convincingly that levocetirizine
      shows a consistent effect on nasal obstruction as early as over the first 2 h and
      sustained over 6 weeks.

PMID- 16911354
TI  - Changes in immune regulation in response to examination stress in atopic and
      healthy individuals.
AB  - BACKGROUND: Stress can aggravate the allergic inflammation, but determinants of
      disturbed immune regulation are largely unknown. OBJECTIVE: To determine systemic
      immunological, local inflammatory and functional airway responses to stress in
      healthy and atopic individuals. METHODS: Forty-one undergraduate students, 22
      with allergy of whom 16 had asthma, and 19 healthy controls, were studied in a
      low-stress period and in association with a large exam. Subjects completed
      questionnaires on stress and health behaviours, underwent lung function tests,
      bronchial methacholine challenge, measurements of exhaled nitric oxide and urine
      cortisol. Blood cells were phenotyped, and cytokines from mononuclear blood cells
      were analysed. RESULTS: Perceived stress and anxiety increased in both groups
      during the exam period while cortisol increased only in the atopy group. Cytokine
      production decreased broadly in response to stress in both groups, which was
      paralleled by an increase in the proportion of regulatory T cells
      (CD4(+)CD45RO(+)CD25(bright)). Interestingly, atopic individuals, but not
      controls, reacted with a decreased T-helper type 1/T-helper type 2 (Th1/Th2)
      ratio and a decrease in natural killer (NK) cell numbers in response to stress.
      In control subjects only, exhaled nitric oxide decreased and forced expiratory
      volume in one second increased during stress. CONCLUSION: Atopic and non-atopic
      subjects shared some immune changes in response to stress, such as a dramatic
      decline in cytokines and an increase in the number of regulatory T cells in
      peripheral blood. However, other stress-induced immune changes were unique to
      atopic individuals, such as a skewed Th1/Th2 ratio and reduced NK cell numbers,
      indicating that some pathogenic mechanisms in atopics may be more strongly
      affected by stress than others.

PMID- 16911355
TI  - Associations between antioxidant status, markers of oxidative stress and immune
      responses in allergic adults.
AB  - BACKGROUND: There has been growing interest in the role of antioxidant function
      in controlling inflammatory disease states, such as allergy. This study
      investigated the relationship between antioxidant status, markers of airways
      inflammation [exhaled nitric oxide (eNO)], oxidative stress (F(2) isoprostanes)
      and immune responses in allergic adults. METHODS: Antioxidants (vitamins C, E,
      beta-carotene and selenium) and total antioxidant capacity (tAC) in serum were
      examined in relation to eNO, plasma F(2) isoprostanes and peripheral blood
      mononuclear cell (PBMC) cytokine and lymphoproliferative response to house dust
      mite (HDM) allergen, Staphylococcus enterotoxin B (SEB), phytohaemaglutinin (PHA)
      and lipopolysaccharide (LPS) in 54 allergic adults. RESULTS: Firstly, levels of
      specific vitamins did not correlate with tAC. Secondly, we did not see any
      evidence that specific vitamin levels (or tAC) were associated with either
      polarization or attenuation of in vitro immune responses. If anything, there were
      positive correlations between antioxidant (vitamin C and selenium) levels and HDM
      allergen responses [lymphoproliferation (selenium; r=0.35, P=0.013) and both Th2
      IL13 (vitamin C; tau=0.254, P=0.028) and Th1 IFN-gamma (vitamin C; tau=0.302,
      P=0.009) responses]. There were also significant positive relationships between
      antioxidant levels and IL-10 responses to polyclonal stimulation by SEB (r=0.292,
      P=0.036) and LPS (r=0.34, P=0.015) (beta-carotene) and PHA (r=0.34, P=0.021)
      (tAC). Thirdly, although airways inflammation (eNO) was associated with both in
      vitro and in vivo (skin test reactivity) to HDM, we did not see any correlation
      between eNO and oxidative stress (F(2)-isoprostanes). Finally, there were no
      consistent relationships between oxidative stress and immune responses.
      CONCLUSION: There was no evidence that higher antioxidant levels were associated
      with reduced allergen responsiveness in allergic adults. If anything, antioxidant
      status was associated with increased immune responsiveness. The significance of
      this needs to be addressed in future intervention studies.

PMID- 16911356
TI  - Stress induces substance P in vagal sensory neurons innervating the mouse
      airways.
AB  - BACKGROUND: Tachykinins-like substance P (SP) have been shown to play an
      important role in initiating and perpetuating airway inflammation. Furthermore,
      they are supposed to be released into tissues in response to stress. OBJECTIVE:
      The aim of this study was to investigate the effects of stress alone or in
      combination with allergic airway inflammation on SP expression in sensory neurons
      innervating the mouse airways. METHODS: Balb/c mice were systemically sensitized
      to ovalbumin (OVA), followed by allergen aerosol exposure, and compared with non
      sensitized controls. Additionally, OVA-sensitized and -challenged and non
      sensitized mice were exposed to sound stress. SP expression in airway-specific
      and overall vagal sensory neurons of the jugular and nodose ganglion complex was
      analysed using retrograde neuronal tracing in combination with
      immunohistochemistry. Preprotachykinin A (PPT-A) mRNA, the precursor for SP, was
      quantified in lung tissue by real-time PCR. Bronchoalveolar lavage (BAL) fluid
      was obtained, and cell numbers and differentiation were determined. RESULTS:
      Stress and/or allergic airway inflammation significantly increased SP expression
      in retrograde-labelled vagal sensory neurons from the mouse lower airways
      compared with controls [stress: 15.7+/-0.8% (% of retrograde-labelled neurons,
      mean+/-SEM); allergen: 17.9+/-0.4%; allergen/stress: 13.1+/-0.7% vs. controls:
      6.3+/-0.3%]. Similarly, SP expression increased in overall vagal sensory neurons
      identified by the neuronal marker protein gene product (PGP) 9.5 [stress: 9.3+/
      0.6% (% of PGP 9.5-positive neurons, means+/-SEM); allergen: 12.5+/-0.4%;
      allergen/stress: 10.2+/-0.4% vs. controls: 5.1+/-0.3%]. Furthermore, stress
      significantly increased PPT-A mRNA expression in lung tissue from OVA-sensitized
      and -challenged animals, and immune cells were identified as an additional source
      of SP in the lung by immunohistochemistry. Associated with enhanced neuronal SP
      expression, a significantly higher number of leucocytes were found in the BAL
      following allergen exposure. Further, stress significantly increased allergen
      induced airway inflammation identified by increased leucocyte numbers in BAL
      fluids. CONCLUSION: The central event of sound stress leads to the stimulation of
      SP expression in airway-specific neurons. However, in sensitized stressed mice an
      additional local source of SP (probably inflammatory cells) might enhance
      allergic airway inflammation.

PMID- 16911357
TI  - Prolonged exclusive breastfeeding is associated with increased atopic dermatitis:
      a prospective follow-up study of unselected healthy newborns from birth to age 20
      years.
AB  - BACKGROUND: Exclusive breastfeeding for the first 6 months is recommended by the
      World Health Organization and considered allergy preventive. However, it is not
      known whether prolonging exclusive breastfeeding for over 6 months provides
      further benefit in allergy prevention. OBJECTIVE: The aim of this prospective 20
      year follow-up study was to find out whether the allergy protective effect can be
      enhanced by prolonging strictly exclusive breastfeeding for > or =9 months of
      age. A total of 200 unselected healthy newborns were enrolled in the study. Their
      mothers were encouraged to maintain exclusive breastfeeding for as long as
      possible. The number of infants on strictly exclusive breastfeeding was 167 at 2,
      116 at 6, 36 at 9 and 7 at 12 months of age. Of the 200 infants, 42% had a family
      history of allergy. The children were re-assessed at ages 5 (n=163), 11 (n=150)
      and 20 years (n=164) with clinical examination, skin prick testing, and parental
      and personal structured interviews. RESULTS: Exclusive breastfeeding prolonged
      for > or =9 months was associated with atopic dermatitis (P=0.002) and symptoms
      of food hypersensitivity (P=0.02) at age 5 years, and with symptoms of food
      hypersensitivity at age 11 years (P=0.01), in children with a family history of
      allergy. CONCLUSION: Prolonging strictly exclusive breastfeeding for > or =9
      months was not helpful in atopy prevention, instead, it was associated with
      increased atopic dermatitis and food hypersensitivity symptoms in childhood.

PMID- 16911358
TI  - Total serum immunoglobulin E levels in a case-control study in asthmatic/allergic
      patients, their family members, and healthy subjects from India.
AB  - BACKGROUND: Total immunoglobulin E (IgE) is an important indicator of allergic
      disorders. However, its role in allergic patients in India has not been evaluated
      in relation to atopic status for a reference range as compared with healthy
      subjects. OBJECTIVE: The aim of the study was to establish serum IgE levels in a
      diseased group, study its relationship with atopy, and to compare the same with
      healthy volunteers in Indian subjects. METHODS: Four hundred and eighty
      asthmatics/allergic patients, 100 first-degree relatives of asthmatics, and 120
      unrelated normal healthy volunteers from Delhi region were recruited for the
      study. Atopy was established by family history and skin test to common indigenous
      allergens and, total and specific IgE measurements. Statistical analysis was
      performed with the help of SPSS software program. RESULTS: The mean IgE levels
      were the highest in asthmatic patients and the lowest in the control healthy
      group. IgE was significantly high in the male than the female healthy volunteers
      (P<0.05), but not in the diseased group. Prosopis juliflora among pollen
      allergens and Alternaria alternata among fungal allergens were important
      sensitizers in allergic patients with 34.7% and 17.7% skin positivity,
      respectively. Atopic status and asthma were found to be the best predictor of
      IgE, which was highly significant (r(2)=0.239, P<0.00001). However, at 95%
      confidence interval as many as 50% of asthmatic patients had their IgE values in
      the normal range. CONCLUSION: The IgE levels in Indian allergic patients is
      significantly related to atopy, but due to wide overlap of IgE levels in patients
      and healthy subjects, its diagnostic significance in Indian population seems to
      be limited.

PMID- 16911359
TI  - Role of prostaglandin D2 and E2 terminal synthases in chronic rhinosinusitis.
AB  - BACKGROUND: Prostaglandin (PG)D(2) and E(2), two major cyclooxygenase (COX)
      products, are generated by PGD(2) synthase (PGDS) and PGE(2) synthase (PGES),
      respectively, and appear to mediate airway inflammation. OBJECTIVE: We sought to
      determine the role of PGDS and PGES in the pathophysiology of chronic
      rhinosinusitis (CRS). METHODS: The study examined the expression of PGDS and PGES
      in nasal polyps of 22 CRS patients. As controls, uncinate process mucosae were
      obtained from 12 CRS patients not having nasal polyps and five subjects without
      sinusitis. Immunohistochemistry and quantitative real-time PCR were used to
      evaluate the expression. RESULTS: Both PGDS and PGES were detected in nasal
      polyps by immunohistochemistry. Significantly greater levels of PGDS mRNA and
      lesser levels of PGES mRNA were observed in the nasal polyps as compared with
      uncinate process mucosae, and an inverse correlation between PGDS and PGES
      expression was observed. Levels of PGDS mRNA in nasal polyps were positively
      correlated with degree of infiltration by EG2+ eosinophils, whereas the levels of
      PGES were inversely correlated. Significantly increased levels of PGDS and
      conversely decreased levels of PGES were observed in asthmatics as compared with
      non-asthmatics. In addition, PGDS and PGES levels were positively and inversely
      correlated with the radiological severity of sinusitis, respectively.
      CONCLUSIONS: These results suggest that PGDS and PGES display an opposite and
      important role in the pathophysiology of CRS such as polyp formation, and more
      specifically, a biased expression of these synthases might contribute to the
      development of CRS by affecting eosinophilic inflammation.

PMID- 16911360
TI  - Gene and protein expression of protease-activated receptor 2 in structural and
      inflammatory cells in the nasal mucosa in seasonal allergic rhinitis.
AB  - BACKGROUND: Protease-activated receptor 2 (PAR 2) has been shown to be
      responsible for trypsin and mast cell tryptase-induced airway inflammation. Here,
      the present study aimed to explore the expression of PAR 2 in the nasal mucosa of
      seasonal allergic rhinitis (SAR). METHODS: Study subjects were recruited for the
      study by medical history, physical examination and laboratory screening tests.
      Using immunohistochemistry, laser-assisted cell picking and subsequently real
      time PCR, nasal mucosa biopsies of SAR patients were investigated for PAR 2 gene
      and protein expression in complex tissues of the nasal mucosa. RESULTS: Gene and
      protein expression of PAR 2 was firstly detected in nasal mucosa of SAR patients.
      The relative gene expression level of PAR 2 was significantly increased in
      complex tissues of the nasal mucosa of SAR (6.21+/-4.02 vs. controls: 1.38+/
      0.86, P=0.004). Moreover, PAR 2 mRNA expression in epithelial cells (SAR: 4.78+/
      4.64 vs. controls: 0.84+/-0.61, P=0.003) but not in mucus (SAR: 1.51+/-1.15 vs.
      controls: 1.35+/-1.02, P=0.78) and endothelial cells (SAR: 1.20+/-0.57 vs.
      controls: 1.73+/-1.30, P=0.5) was found to be significantly changed in the nasal
      mucosa in SAR. Using double immunohistochemistry the present study demonstrated
      that the total numbers of mast cells (P=0.0003) and eosinophils (P=0.03) and the
      numbers of eosinophils expressing PAR 2 (P=0.006) were significantly elevated in
      the nasal mucosa of SAR compared with the controls. CONCLUSION: The abundant
      presence and distribution of gene and protein expression of PAR 2 in different
      cell types in the nasal mucosa under normal situation, the increased expression
      of PAR 2 in epithelial cells and the increased number of eosinophils with PAR 2
      suggest that PAR 2 may contribute to the pathogenesis of allergic diseases such
      as SAR.

PMID- 16911361
TI  - Synthetic double-stranded RNA induces multiple genes related to inflammation
      through Toll-like receptor 3 depending on NF-kappaB and/or IRF-3 in airway
      epithelial cells.
AB  - BACKGROUND: We hypothesized that synthetic double-stranded (ds)RNA may mimic
      viral infection and induce expression of genes related to inflammation in airway
      epithelial cells. OBJECTIVE: We analysed what gene was up-regulated by synthetic
      dsRNA poly I : C and then focused this study on the role of Toll-like receptor 3
      (TLR3), a receptor of dsRNA and its transcriptional pathway. METHODS: Airway
      epithelial cell BEAS-2B and normal human bronchial epithelial cells were cultured
      in vitro. Expression of targets RNA and protein were analysed by PCR and ELISA.
      Localization of TLR3 expression in the cells was analysed with flow cytometry. To
      analyse the role of TLR3 and transcription factors, knockdown of these genes was
      performed with short interfering RNA (siRNA). RESULTS: Real-time PCR revealed
      that poly I : C significantly increased the expression of mRNAs for chemokines IP
      10, RANTES, LARC, MIP-1alpha, IL-8, GRO-alpha and ENA-78 and cytokines IL-1beta,
      GM-CSF, IL-6 and the cell adhesion molecule ICAM-1 in both cell types. Increases
      in protein levels were also observed. Expression of these genes was significantly
      inhibited in BEAS-2B cells in which TLR3 expression was knocked down. However,
      pre-treatment with anti-TLR3 mAb, which interferes with the function of TLR3
      expressed on the cell surface, did not inhibit the genes expression and these
      data were concordant with the results that TLR3 was expressed inside airway
      epithelial cells. The study of siRNA for NF-kappaB and IRF3 showed that they
      transduce the signal of poly I : C, but their roles were different in each target
      gene. CONCLUSION: TLR3 is expressed inside airway epithelial cells and transduces
      synthetic dsRNA signals. These signals may increase expression of inflammatory
      cytokines, chemokines and ICAM-1 through activation of transcription factors NF
      kappaB and/or IRF3 in airway epithelial cells.

PMID- 16911362
TI  - Aggravation of bronchial eosinophilia in mice by nasal and bronchial exposure to
      Staphylococcus aureus enterotoxin B.
AB  - BACKGROUND: The role of bacterial enterotoxins like Staphylococcus aureus
      enterotoxin B (SEB) in allergic asthma remains unknown. We used a mouse model of
      airway allergy to study the effects of nasal or bronchial contact with SEB on
      bronchial allergic inflammation. METHODS: The features of allergic asthma were
      induced in ovalbumin (OVA)-sensitized mice (days 1-13) by repeated exposures to
      nebulized OVA (days 33-37). Nasal or bronchial application of SEB was performed
      on three occasions (days 33-35-37), and the effects on bronchial inflammation,
      IgE titres and expression levels of mRNA for T helper type 2 cytokines and other
      inflammatory mediators were evaluated. RESULTS: Both nasal and bronchial SEB
      enhanced the allergen-induced bronchial inflammation, as reflected by more
      eosinophilic inflammation in the airway lumen and in bronchial tissue.
      Aggravation of experimental asthma correlated with higher expression of mRNA for
      IL-5, IL-4, IFN-gamma, IL-12 p40, eotaxin-1 and TGF-beta in bronchi. In addition,
      nasal SEB elevated concentrations of IL-4, IL-5 and IFN-gamma in serum and
      bronchial SEB increased titres of OVA-specific and total IgE in serum.
      CONCLUSION: Our data illustrate the potential of both nasal as well as bronchial
      SEB to aggravate several features of allergic asthma in a mouse model.

PMID- 16911363
TI  - Diagnosis of iodinated contrast media hypersensitivity: results of a 6-year
      period.
AB  - BACKGROUND: Iodinated contrast media (ICM) hypersensitivity reactions represent a
      serious problem. Very few clinical data concerning systematic skin testing to ICM
      are available. OBJECTIVE: To evaluate the utility of ICM skin testing in patients
      with ICM hypersensitivity. MATERIAL AND METHODS: All patients referred over a 6
      year period for ICM hypersensitivity past reactions were skin tested for (a) the
      implicated ICM, or (b) a set of ICM if they were positive for the implicated ICM
      or if its name was unknown. RESULTS: Forty-four patients, with a median age of 56
      years, were studied (15 males, 29 females). The ICM skin tests were positive in
      10 patients (23%): one had a positive skin prick test, seven an immediate
      positive intradermal test (IDT) and two a delayed positive IDT. Skin tests were
      more often positive in patients with immediate (9/32) as compared with those with
      non-immediate reactions (1/11). The time interval between the reaction and skin
      testing was shorter for those patients with an immediate ICM reaction and a
      positive skin test result (3 months [2.5-174.0]) as compared with those with an
      immediate ICM reaction and a negative skin test (48 months [6.8-159.0]),
      (P<0.05). Respiratory allergy was more frequent in the positive group (6/10 vs.
      7/34, P<0.05). CONCLUSIONS: Skin tests with ICM are positive in a subgroup of
      patients with ICM hypersensitivity and may play an important role in the
      diagnosis of ICM allergy.

PMID- 16911364
TI  - Allergen concentration in natural rubber latex.
AB  - BACKGROUND: Hevea brasiliensis latex serum is commonly used as the in vivo and in
      vitro reference antigen for latex allergy diagnosis as it contains the full
      complement of latex allergens. OBJECTIVE: This study quantifies the
      concentrations of the significant allergens in latex serum and examines its
      suitability as an antigen source in latex allergy diagnosis and immunotherapy.
      METHODS: The serum phase was extracted from centrifuged latex that was repeatedly
      freeze-thawed or glycerinated. Quantitation of latex allergens was performed by
      two-site immunoenzymetric assays. The abundance of RNA transcripts of the latex
      allergens was estimated from the number of their clones in an Expressed Sequence
      Tags library. RESULTS: The latex allergens, Hev b 1, 2, 3, 4, 5, 6, 7 and 13,
      were detected in freeze-thawed and glycerinated latex serum at levels ranging
      from 75 (Hev b 6) to 0.06 nmol/mg total proteins (Hev b 4). Hev b 6 content in
      the latex was up to a thousand times higher than the other seven latex allergens,
      depending on source and/or preparation procedure. Allergen concentration was
      reflected in the abundance of mRNA transcripts. When used as the antigen, latex
      serum may bias the outcome of latex allergy diagnostic tests towards
      sensitization to Hev b 6. Tests that make use of latex serum may fail to detect
      latex-specific IgE reactivity in subjects who are sensitized only to allergens
      that are present at low concentrations. CONCLUSION: Latex allergy diagnostics and
      immunotherapy that use whole latex serum as the antigen source may not be optimal
      because of the marked imbalance of its constituent allergens.

PMID- 16911365
TI  - Characterization of recombinant Mal d 4 and its application for component
      resolved diagnosis of apple allergy.
AB  - BACKGROUND: Profilins are ubiquitous panallergens that have been extensively
      characterized; yet, their clinical relevance is still unclear. OBJECTIVE: The aim
      of the present study was to produce recombinant apple profilin (rMal d 4) and to
      evaluate its allergenic activity and its potency for component-resolved allergy
      diagnosis. METHODS: Complementary DNA-derived Mal d 4 was cloned, expressed in
      Escherichia coli and subsequently purified via poly (l-proline) sepharose. A
      total of 28 sera from apple-allergic patients were used for IgE-ELISA,
      immunoblot, RAST and basophil histamine release (BHR) test. In addition, skin
      prick tests (SPTs) were performed in five patients. RESULTS: Four different
      complementary DNA coding for apple profilin, Mal d 4, each with an open reading
      frame of 393 nucleotides, were identified. One isoform Mal d 4.0101 was expressed
      in Escherichia coli and subsequently purified. Mass spectroscopy revealed the
      expected mass of 13.826 for rMal d 4.0101, and circular dichroism analysis data
      were typical for a folded protein and small-angle X-ray scattering measurement
      identified the protein as a monomer. All the serum samples displayed IgE binding
      to rMal d 4.0101 in IgE ELISA, immunoblot and RAST. In immunoblotting, IgE
      binding to natural Mal d 4 was partially/completely inhibited by preincubation
      with rMal d 4.0101, and RAST values to apple extract were significantly reduced
      upon serum pretreatment with rMal d 4.0101. SPTs and BHR assays using purified
      rMal d 4.0101 were positive. Purified rMal d 4.0101 was destroyed within seconds
      when subjected to pepsin digestion. CONCLUSIONS: Apple profilin complementary
      DNAs were identified. The physicochemical and allergenic properties of purified
      recombinant Mal d 4.0101 were evaluated showing that the recombinant protein was
      equal to the natural protein as shown by inhibition assays. Thus, Mal d 4
      represents another example suitable for component-resolved diagnosis of food
      allergy.

PMID- 16911366
TI  - Mouse allergen-specific immunoglobulin G4 and risk of mouse skin test
      sensitivity.
AB  - BACKGROUND: High serum levels of cat-specific IgG and IgG4 are associated with
      protection against allergic sensitization to cat, but whether this association
      applies to other animal allergens remains unclear. OBJECTIVE: To determine if
      high levels of mouse-specific IgG and IgG4 are associated with a decreased risk
      of mouse skin test sensitivity. METHODS: Two hundred and sixty workers of a mouse
      facility underwent skin prick testing and completed a questionnaire. Serum levels
      of mouse-specific IgG and IgG4 were quantified by solid-phase antigen binding
      assays. Room air samples were collected and airborne Mus m 1 was quantified by
      ELISA. RESULTS: Forty-nine participants had a positive skin prick test to mouse.
      Mouse-specific IgG was detected in 219 (84%) participants and IgG4 was detected
      in 72 (28%) participants. A detectable mouse-specific IgG4 level was associated
      with an increased risk of mouse skin test sensitivity (odds ratios (OR) 6.4, 95%
      confidence intervals (CI) 3.3-12.4). Mouse-specific IgG and IgG4 were both
      positively correlated with mouse allergen exposure (r(s)=0.31, P=0.0001, and
      r(s)=0.27, P=0.0006, respectively). The odds of skin test sensitivity peaked at
      moderate levels of IgG4, but decreased at the highest levels of mouse-specific
      IgG4. In contrast, the odds of skin test sensitivity increased monotonically with
      IgG levels. CONCLUSIONS: A detectable level of mouse-specific IgG4 is associated
      with an increased risk of skin test sensitivity to mouse. However, the highest
      IgG4 levels appear to be associated with an attenuated risk of mouse skin test
      sensitivity, suggesting that induction of high levels of IgG4 through natural
      exposure may protect against the development of allergic sensitization.

PMID- 16911367
TI  - Polymorphisms in manganese superoxide dismutase and catalase genes: functional
      study in Hong Kong Chinese asthma patients.

PMID- 16911369
TI  - Klippel-Trenaunay syndrome: a multisystem disorder possibly resulting from a
      pathogenic gene for vascular and tissue overgrowth.
AB  - Klippel-Trenaunay syndrome is characterized by a triad of varicose veins,
      cutaneous capillary malformation, and hypertrophy of bone and soft tissue.
      Appropriate evaluation and treatment of children displaying features of the
      disease may minimize morbidity. The clinical appearance, etiology, genetics,
      diagnostics, and treatment of Klippel-Trenaunay syndrome are herein explored.

PMID- 16911370
TI  - Head louse infestations: the "no nit" policy and its consequences.
AB  - Health authorities in the USA, Canada and Australia recommend a "no nit" policy,
      i.e. the immediate dismissal of all children who have head lice, eggs and/or nits
      on their hair from school, camp or child-care settings. These children would be
      readmitted to the institution only when all head lice, eggs and nits have been
      removed. The "no nit" policy assumes that all nits seen when examining the scalp
      are viable and therefore the infested individual should be treated for lice, and
      all nits must be removed from the scalp. However, it has been repeatedly shown
      that only a small number of children who have nits on their scalp are also
      infested with living lice. Accordingly, in the USA alone 4-8 million children are
      treated unnecessarily for head lice annually, which amounts to 64% of all lice
      treatments. In addition, 12-24 million school days are lost annually. The annual
      economic loss owing to missed workdays by parents who have to stay home with
      their children adds US$4-8 billion to the country's economy. The policy also
      results in serious psychological problems for children and their parents.
      Therefore, the "no nit" policy should be abandoned and alternative ways of
      examination and treatment for head lice should be found.

PMID- 16911371
TI  - Fixed drug eruption (FDE): changing scenario of incriminating drugs.

PMID- 16911372
TI  - Scurvy: a disease almost forgotten.
AB  - BACKGROUND: Although much decreased in prevalence, scurvy still exists in
      industrialized societies. Few recent large studies have examined its
      pathogenesis, signs, and symptoms. METHODS: After we diagnosed scurvy in a 77
      year-old female patient in 2003, we conducted a retrospective records review to
      identify patients with scurvy treated between 1976 and 2002 at Mayo Clinic
      (Scottsdale, Arizona; Rochester, Minnesota; or Jacksonville, Florida). We also
      searched the English-language medical literature for published reports on scurvy.
      RESULTS: In addition to our patient, seven of 11 patients whose records in the
      institutional database mentioned vitamin C deficiency were women. The age ranged
      from a neonate to 77 years (mean, 48 years). The most common associated causes
      were concomitant gastrointestinal disease, poor dentition, food faddism, and
      alcoholism. Vitamin or mineral deficiencies other than vitamin C deficiency were
      also found in our patients who had scurvy. The most common symptoms were
      bruising, arthralgias, or joint swelling. The most common signs were pedal edema,
      bruising, or mucosal changes. Four patients had vague symptoms of myalgias and
      fatigue without classic findings, and five had concomitant nutritional
      deficiencies. Follow-up available for six of 12 patients treated by vitamin C
      supplementation showed complete resolution of symptoms in five. CONCLUSIONS:
      Patients with scurvy may present with classic symptoms and signs or with
      nonspecific clinical symptoms and an absence of diagnostically suggestive
      physical findings. Concomitant deficiency states occur not uncommonly. Taking a
      thorough dietary history and measuring serum ascorbic acid levels should be
      considered for patients with classic signs and symptoms, nonspecific
      musculoskeletal complaints, or other vitamin or mineral deficiencies.

PMID- 16911373
TI  - Sensitivity of indirect immunofluorescence and ELISA in detecting intercellular
      antibodies in endemic pemphigus foliaceus (Fogo Selvagem).
AB  - BACKGROUND: Since 1967 dermatology has used the classic technique of indirect
      immunofluorescence (IFI) for the detection of autoantibodies against antigens of
      the skin in diseased people with endemic pemphigus foliaceus. Thirty years later
      enzyme-linked immunosorbent assays--ELISA (rDsg1 and rDsg3) appeared as a viable
      option. A group of highly recognized researchers have concluded that ELISA is a
      simple, sensitive and highly specific method, allowing for diagnostic
      differentiation between pemphigus vulgaris (PV) and endemic pemphigus foliaceus
      (EPF). Scientific literature certifies that both ELISA and IIF bear high
      sensitivity in spite of the fact that a direct comparison between the ELISA and
      IIF tests has never been performed. OBJECTIVES: This study was conducted to
      compare the sensitivity of these tests in detecting antibodies in the EPF.
      MATERIAL AND METHODS: Thirty-two serum samples were collected from patients with
      EPF. The control serum of 15 healthy individuals was tested to detect the
      presence of antibodies of EPF by indirect immunofluorescence and ELISA (rDsg1 and
      rDsg3). The IIF was performed, taking human skin as a substrate. RESULTS:
      Antibodies in patients with EPF were detected more commonly by the ELISA (rDsg1)
      (91%) compared with IIF (81%). CONCLUSIONS: The ELISA (rDsg1) is slightly more
      sensitive than IIF in detecting antibodies related to EPV. However, according to
      our results, we do not currently possess a test with 100% accuracy in
      differentiating EPF from PV. Although previous studies have associated Dsg3 with
      PV, the tests performed during this study showed that 12% (4/32) of patients with
      EPF (cutaneous diseases only) also had Dsg3 antibodies.

PMID- 16911375
TI  - A bibliometric study of dermatology in central Europe 1991-2002.
AB  - BACKGROUND: Bibliometric studies have gained interest in recent years, although
      most analyses are limited to simple use of average citations rates for journals,
      also known as the "impact factor". Central Europe has a long tradition of
      dermatological research which has been negatively impacted by general political
      developments for a long period. This study was undertaken in order to describe
      the progress made in recent years. METHODS: The study was conducted in two parts:
      First the annual national output for the period 1991-2002 was identified for each
      country by MEDLINE searches. In the second part of the study a sample was drawn
      from the papers identified in the first part and the number of citations for each
      paper noted. RESULTS: The annual national output showed great variation between
      countries and from year to year. The mean citation rates were found to vary
      between 0-5 citations/year, and some underlying publications were 10 years old.
      Countries with national indexed journals appear to hold a bibliometric advantage
      over countries without indexed journals. CONCLUSIONS: Throughout the last decade
      of the 20th century the number of publications has grown with an average of 21.7%
      per year, and publication rates have only suffered in countries directly involved
      in war or similar disturbances. The mean citation rates were low, with a varying
      age of the underlying publications. Some cited publications were however old
      suggesting a persistent relevance. A national or regional indexed journal appears
      to confer a bibliometric advantage.

PMID- 16911374
TI  - Vascular involvement in Behcet's disease: a retrospective analysis of 2319 cases.
AB  - BACKGROUND: Vascular lesions can be the presenting sign of Behcet's disease (BD)
      preceding classical symptoms. The aim of this study was to evaluate the
      prevalence and types of vascular involvement in BD. METHODS: Among 2319 patients
      diagnosed with BD according to the criteria of the International Study Group for
      BD, 332 patients (279 male, 53 female) with vascular involvement were included in
      this study. RESULTS: Prevalence of vascular involvement was 14.3%. Vascular
      involvement was found to be more common in males (P<0.001, male:female ratio
      5.26:1). Mean age at onset of vascular involvement was 30.58+/-7.88. Vascular
      lesion was the presenting sign of BD in 50 patients (2.1%), whereas in 109
      patients (4.7%) it started together with other clinical symptoms at the age of
      diagnosis. Superficial vein thrombophlebitis (SVT) was the most common vascular
      symptom (53.3%) followed by deep vein thrombosis (DVT) (29.8%). Arterial lesions
      were rare (3.6%). Of the patients 13.3% had more than one type of vascular
      involvement. Lower extremities were the most frequent localization in patients
      with SVT, whereas the femoral vein was mainly involved in patients with DVT and
      the pulmonary artery was mainly involved in the patients with arterial lesions.
      CONCLUSION: In countries like Turkey where BD is more frequent, young male
      patients presenting with vascular involvement should be evaluated for BD.

PMID- 16911376
TI  - Dermatological problems in the football player.

PMID- 16911377
TI  - Etiology and incidence of chronic ulcers in Blantyre, Malawi.
AB  - BACKGROUND: Little information is available on the incidence and etiology of
      chronic ulcers in the tropics. Therefore, the incidence and etiology of chronic
      skin ulcers were assessed in out-patients at the Department of Dermatology and in
      in-patients at the Departments of Dermatology, Surgery, Medicine, and Pediatrics,
      Queen Elizabeth Central Hospital (QECH), Blantyre, Malawi. METHOD: In a 10-week
      study period, 44 patients (31 males, 70%) with chronic skin ulcers were diagnosed
      from 6292 patients seen by the departments involved. RESULTS: The mean age of
      patients with ulcers was 38 years (range, 9 months to 82 years). The most
      frequent cause of ulcers was bacterial infection (n=22), followed by malignancy
      (n=11) and trauma (n=7). CONCLUSION: In contrast with developed countries, venous
      and diabetic ulcers were uncommon. In addition to bacterial infections, a
      surprisingly large number of malignancies were found in this study. We speculate
      that human immunodeficiency virus (HIV) infection, which is seen with a high
      prevalence at QECH, is a contributing factor. Because of the large number of
      malignancies, we recommend early histopathologic investigation of chronic ulcers
      in this part of Africa.

PMID- 16911378
TI  - Immunopathologic study of erythema dyschromicum perstans (ashy dermatosis).
AB  - Erythema dyschromicum perstans (EDP) is a pigmentary disease of unknown etiology
      in which damage to basal cells is thought to be mediated by adhesion molecules.
      The aim of this study was to characterize the histopathology and immunopathology
      of EDP. Forty-three patients from Medellin, Colombia, with the diagnosis of EDP
      were evaluated. Skin biopsy specimens were obtained for histopathology and
      immunohistochemistry, using monoclonal antibodies directed against the following
      markers: CD4, CD8, CD56, CD1a, CD68, CLA, HLA-DR, ICAM-1 and LFA-1alpha. A dermal
      lymphocytic infiltrate was observed in all cases, with a perivascular location in
      86%. Other histologic features included melanophages in all specimens,
      vacuolization of the basement membrane zone (BMZ) 58% and exocytosis of
      lymphocytes (53.5%). The mean number of total leukocytes was 1510 cells mm-2 of
      tissue. There was a predominance of CD8+ T lymphocytes in the dermis and HLA-DR+,
      ICAM-1+ keratinocytes in the epidermis. Exocytosis of cutaneous lymphocyte
      antigen (CLA)+cells was observed in areas of BMZ damage, suggesting that response
      to antigenic stimulation may play a role in the development of EDP.

PMID- 16911379
TI  - Disseminated Acanthamoeba infection with sporotrichoid nodules.

PMID- 16911380
TI  - Discoid lupus erythematosus presenting as acneiform pitting scars.

PMID- 16911381
TI  - Cutaneous metastasis to the chest wall from prostate cancer.

PMID- 16911382
TI  - Cutis laxa acquisita associated with cutaneous mastocytosis.

PMID- 16911383
TI  - Regressing cutaneous malignant melanoma and vitiligo-like depigmentation.

PMID- 16911384
TI  - Intraepidermal animal-type melanoma.
AB  - Animal-type melanoma is a rare variant of melanoma in humans.1 Its name is
      derived from its histological appearance, which is similar to that described in
      melanomas occurring in white or gray horses.2 All tumors are dermally located,
      and characterized by a proliferation of deeply pigmented elongated or rounded
      cells, showing moderate atypia and a low mitotic rate. In some tumors, secondary
      infiltration of the epidermis has been noted. More than half of the patients are
      younger than 30 years, and prognosis seems to be much better than that expected
      for a superficial spreading or nodular melanoma of the same size. We report the
      first case of animal-type melanoma in situ.

PMID- 16911385
TI  - Unilateral nevoid telangiectasia--response to pulsed dye laser.
AB  - BACKGROUND: Unilateral nevoid telangiectasia (UNT) is a unique vascular
      dermatosis of ambiguous etiology. The therapeutic role of pulsed dye laser in
      this condition, especially in individuals with skin types III and IV, has not
      been elucidated completely. The aim of this study was to assess the response to
      flash-lamp pulsed dye laser of UNT in Indian patients. METHODS: A detailed
      analysis of nine confirmed cases of UNT patients was undertaken to determine the
      possible etiologic association of this disease. Six cases were treated with
      pulsed dye laser in combination with cryogen cooling using the following
      parameters: spot size, 7 mm; fluence, 5-7.5 J/cm2; wavelength, 585 nm; pulse
      duration, 450 micros. The procedure was repeated every 4-6 weeks and the response
      was assessed both clinically and photographically before each session. RESULTS:
      The cases had a mean age of presentation of 20.6 years with an age of onset
      varying from 2.5 to 23 years. The lesions were located on the head and neck
      region in four patients, upper limb in four, and lower limb in one. No
      significant etiologic association could be established. Of the six cases treated
      with pulsed dye laser, a moderate response (26-50% lightening) was achieved in
      all cases after a mean of 2.33 sessions, a good response (51-75% lightening) was
      observed in four patients after 3.25 sessions, and an excellent response (>75%
      lightening) was found in three patients after 3.66 sessions. Mild and reversible
      pigmentary alterations occurred in five cases, with mild textural change in one
      case. There was no scarring. No recurrence was observed. CONCLUSION: Pulsed dye
      laser is a useful modality for treating UNT in Indian patients. Reversible
      pigmentary changes are the major side-effects.

PMID- 16911386
TI  - The treatment of psoriasis vulgaris: 1% topical methotrexate gel.
AB  - BACKGROUND: In general, 70% of patients with psoriasis prefer topical therapy as
      the treatment of choice. AIM: To evaluate the efficacy and tolerability of 1%
      topical methotrexate gel vs. placebo (vaseline ointment) as treatment for
      psoriasis. METHODS: Forty patients (20 females and 20 males) with chronic plaque
      type psoriasis joined the study. Each patient was allocated to apply 1%
      methotrexate gel and placebo topically to their two target lesions, equal in area
      and disease severity, twice daily for 8 weeks. Lesions were scored at baseline
      and after 2, 4, 6, and 8 weeks of treatment for erythema, scale, and
      infiltration. The global improvement and histopathologic features were also
      assessed after methotrexate treatment. RESULTS: At the end of treatment, erythema
      was cleared totally in 47.5% of patients treated with methotrexate vs. 7.5% of
      those treated with placebo, and infiltration in 22% of patients treated with
      methotrexate vs. 2.5% of those treated with placebo (P<0.01). Clinical
      improvement was almost the same for the two groups with regard to scale (P<0.5).
      The global improvement was 97% for patients treated with methotrexate vs. 60% for
      those treated with placebo, and a significant difference was found between the
      groups (P<0.01). Histopathologic improvement was achieved in the methotrexate
      group (P<0.01). No side-effects were observed. CONCLUSION: The findings of this
      study suggest that methotrexate 1% in a hydrophilic gel is well tolerated and
      significantly more effective than placebo as a topical medication for the
      treatment of psoriasis vulgaris.

PMID- 16911387
TI  - Retrospective assessment of PASI 50 and PASI 75 attainment with a
      calcipotriol/betamethasone dipropionate ointment.
AB  - BACKGROUND: The US National Psoriasis Foundation recently recommended that PASI
      50 and PASI 75 response rates be used in clinical trials to enable comparisons
      across studies of different psoriasis therapies. To date, these response rates
      have not been reported for the two-compound ointment containing calcipotriol and
      betamethasone dipropionate (Daivobet/Dovobet; LEO Pharma, Ballerup, Denmark).
      Further, in order to compare Daivobet with other therapeutics recently presented
      to the European regulatory authorities and the FDA, comparison with the
      biologicals, efalizumab, etanercept and alefacept, were also made. OBJECTIVES: To
      present the PASI 50 and PASI 75 results for the two-compound ointment containing
      calcipotriol and betamethasone dipropionate. METHODS: Data from six phase III
      studies conducted with the two-compound ointment were pooled and the PASI 50 and
      PASI 75 response rates calculated for patients with severe (PASI>or=17) or less
      severe disease (PASI<17) at treatment commencement. Results for the biological
      therapies, efalizumab, etanercept and alefacept, were obtained from relevant
      published phase III studies. RESULTS: PASI 50 and PASI 75 were achieved by more
      patients treated with the two-compound ointment than with the individual
      components. In patients with severe disease, the PASI 50 response rate after 4
      weeks' treatment was 88.8% with the two-compound ointment, 69.2% with
      betamethasone dipropionate, 53.8% with calcipotriol, and 30.0% with ointment
      vehicle. In comparison, 12 weeks' treatment with the biologicals resulted in PASI
      50 response rates of 59% with efalizumab, 74% with etanercept, and 56% with
      alefacept. CONCLUSIONS: The two-compound ointment is effective, producing a PASI
      50 and PASI 75 response in greater than 80% and 50% of patients, respectively,
      regardless of psoriasis severity.

PMID- 16911390
TI  - Nehushtan: the pressing need.

PMID- 16911388
TI  - 1599: first iconographic description of hepatoerythropoietic porphyria.
AB  - The author's aim was to contribute information to the history of porphyrias
      through the analysis of a 16th century portrait. The subject drawn by physician
      Aldrovandi is a 20-year-old girl showing remarkable facial hypertrichosis, while
      her body is described as hairless. After a brief excursus through the history of
      porphyrias, the author revisited a previous diagnosis of hypertrichosis
      lanuginosa with the aid of current clinical findings. Accurate research of the
      drawings by the 16th century physician together with the study of our case's
      family history have supplied information on the young woman affected by
      hirsutism, such as the absence of hair on her body surface. Careful observation
      together with updated knowledge resulted in a diagnosis of hepatoerythropoietic
      porphyria; a disease characterized by severe facial hypertrichosis, a hairless
      body, and very early onset and heredity.

PMID- 16911391
TI  - Anti-TNF-alpha-induced psoriasis: case report of an unusual adverse event.

PMID- 16911392
TI  - Unmasking of mixed connective tissue disease by adjuvant IFN alpha therapy for
      melanoma.

PMID- 16911393
TI  - Treatment of inguinal hyperhidrosis with botulinum toxin type A.

PMID- 16911394
TI  - Oral lichen planus: clinical and histological evaluation in an open trial using a
      low molecular weight heparinoid (sulodexide).

PMID- 16911395
TI  - The therapeutic effect of combined cryotherapy, paramomycin, and intralesional
      meglumine antimoniate in treating lupoid leishmaniasis and chronic leishmaniasis.

PMID- 16911396
TI  - Increased tumor necrosis factor alpha (TNF-alpha) and interleukin 1 alpha (IL1
      alpha) levels in the lesional skin of patients with nonsegmental vitiligo.

PMID- 16911397
TI  - Multiple trichogranulomas in a hairdresser.

PMID- 16911398
TI  - Hepatitis C virus is not a cofactor for Kaposi's sarcoma development in HIV
      infected patients.

PMID- 16911400
TI  - Cutaneous small vessel vasculitis and pulmonary tuberculosis: an unusual
      association.

PMID- 16911399
TI  - Vancomycin-associated linear IgA bullous dermatosis mimicking toxic epidermal
      necrolysis.

PMID- 16911401
TI  - Pathogenesis and histogenesis of basal cell carcinoma.

PMID- 16911402
TI  - Testing for HIV prior to methotrexate administration. Is it an obligatory
      procedure?

PMID- 16911403
TI  - An atypical varicella exanthem associated with the use of infliximab.

PMID- 16911404
TI  - Naevoid psoriasis? Unilateral psoriasis?

PMID- 16911405
TI  - Actinic radiation plays a significant role in the etiology of actinic granuloma
      lesions.

PMID- 16911406
TI  - Adverse reactions to gefitinib (Iressa): revealing sycosis- and pyoderma
      gangrenosum-like lesions.

PMID- 16911407
TI  - Fixed drug reaction may be sexually induced.

PMID- 16911409
TI  - Microbubble ultrasound: how can it help detect melanoma metastasis?

PMID- 16911410
TI  - Cutaneous manifestations of HIV in Kwa-Zulu Natal, South Africa.

PMID- 16911411
TI  - Pemphigus vegetans confined to the scalp.

PMID- 16911412
TI  - Long-term prurigo in a returned expatriate with chronic strongyloidiasis.

PMID- 16911413
TI  - Atopy in Behcet's disease.

PMID- 16911414
TI  - Ethics in the dental profession-2006.

PMID- 16911415
TI  - Caries detection with laser fluorescence.

PMID- 16911416
TI  - Incidence of noncarious cervical lesions and their relation to the presence of
      wear facets.
AB  - PROBLEM: Noncarious cervical lesions are characterized by loss of tooth structure
      in the cervical area, compromising its integrity and resulting in esthetic
      problems for the patient. PURPOSE: The purpose of this study was to assess
      noncarious cervical lesions in young patients in an attempt to establish a
      possible relationship to the presence of wear facets. MATERIALS AND METHODS:
      First-year dental students of Bauru Dental School were studied to verify the
      prevalence of noncarious cervical lesions and their relationship to the presence
      of wear facets. After 3 years, the students were examined again to verify the
      incidence of new lesions, trying to establish a correlation to the previous
      existence of wear facets. RESULTS: Of the 1,131 teeth analyzed, 129 had
      noncarious cervical lesions. Twenty-nine of the 40 students had at least one
      tooth with one lesion. After 3 years, the incidence of new lesions was 57.
      Mandibular first molars (22.3%), mandibular first premolars (13.2%), mandibular
      second premolars (13.2%), and maxillary first molars (12.4%) showed the highest
      prevalence of lesions. On final analysis, 86.8% of all teeth presenting lesions
      showed wear facets. The identification of new lesions associated with the
      presence of wear facets identified during the first exam 3 years earlier was
      statistically significant (p < 0.01). CONCLUSIONS: The patterns of wear facets
      found in the study population examined were associated with an increased
      occurrence of noncarious cervical lesions. CLINICAL SIGNIFICANCE: Occlusal
      factors, especially the presence of wear facets, should be considered in the
      management of noncarious cervical lesions.

PMID- 16911418
TI  - Patient-dentist-technician communication within the dental team: Using a colored
      treatment plan wax-up.
AB  - Communication among the restorative dental team must include the patient. The
      patient wants to know the details of the anticipated restorations; but because a
      patient is not aware of many dental innovations, care must be taken to provide
      them with a clear explanation of all anticipated treatment parameters. Many
      patients have little understanding of today's advancements in restorative
      procedures, and they may or may not understand all of the possibilities. Through
      effective communication, the patient gains confidence in the dental team and
      better understands the proposed restorative treatment. Patient satisfaction is
      significantly enhanced through effective communication. CLINICAL SIGNIFICANCE:
      This article describes the use of a diagnostic wax-up to facilitate optimal
      communication between the dental team and the patient.

PMID- 16911420
TI  - Correlation between facial measurements and the mesiodistal width of the
      maxillary anterior teeth.
AB  - One of the most difficult aspects during the selection of maxillary anterior
      teeth for a removable prosthesis is determining the appropriate mesiodistal width
      of the six maxillary anterior teeth. Many attempts have been made to establish
      methods of estimating the combined width of these anterior teeth, and improving
      the esthetic outcome. The proportion of facial structures and the relationship
      between facial measurements and natural teeth could be used as a guide in
      selecting denture teeth. The aim of this study was to verify the relation between
      the combined mesiodistal width of the six maxillary anterior teeth and the facial
      segments: the width of the eyes, the inner canthal distance (ICD), the
      interpupillary distance (IPD), the interalar width, and the intercommissural
      width (ICm). Standardized digital images of 81 dentate Brazilian subjects were
      used to measure both facial and oral segments when viewed from the frontal aspect
      through an image processing program. To measure the distance between the upper
      canines on a curve, accurate casts were made from the upper right first premolar
      to the upper left first premolar. The Spearman rank correlation coefficient was
      conducted to measure the strength of the associations between the variables
      (alpha = 0.05). The results showed a significant correlation between all facial
      elements and the combined mesiodistal width of the six teeth, when observed from
      the frontal aspect. The ICD, IPD, and ICm showed the highest probability of being
      correlated to the mesiodistal width of the teeth (p = 0.000). CLINICAL
      SIGNIFICANCE: This article considers facial analysis with digital photography as
      a practical and efficient application to select the mesiodistal width of
      artificial anterior teeth in an esthetically pleasing and natural appearance
      during an oral rehabilitation treatment.

PMID- 16911422
TI  - Remineralization potential of a fluoridated carbamide peroxide whitening gel.
AB  - PURPOSE: Little knowledge exists regarding the potential remineralizing benefits
      of adding fluoride to carbamide peroxide-based whitening gels. The aim of this
      project was to evaluate whether a whitening system with fluoride will
      remineralize previously demineralized enamel. MATERIALS AND METHODS: Twenty-four
      extracted teeth were sectioned into quadrants labeled A to D. Tooth quadrants in
      groups A, B, and D were demineralized with a lactic acid, methyl-cellulose gel
      system to mimic incipient carious lesions. Group C was neither demineralized nor
      treated. Group D was demineralized, but not treated with a whitening gel. Groups
      A and B were exposed to one of two commercially prepared 10% carbamide peroxide
      whitening gels: one that was fluoride free (group A) and one that contained
      fluoride (0.463%NaF) (group B). Remineralization was evaluated histologically and
      analyzed statistically using paired t tests accepting p < 0.05 as significant.
      RESULTS: Shade comparisons showed equal whitening efficacy of both gel A and B.
      Paired t tests show a significant reduction in lesion depth after treatment with
      the fluoride containing gel (B: mean lesion depth = 100 microm; p < 0.01), while
      there was no difference for the gel lacking fluoride (A: mean lesion depth = 110
      microm). CONCLUSION: Under the conditions of this study, the addition of fluoride
      to a tooth whitening system does not affect the gel's whitening efficacy. The
      addition of fluoride could provide remineralization properties to the gel. As
      tooth whitening therapies continue to grow and evolve, a strong focus should rest
      on improving these materials in ways that will provide ever greater patient
      benefits. Coupling the esthetic benefits of whitening with the preventive
      benefits of fluoride is a natural step in this direction. CLINICAL SIGNIFICANCE:
      Therapuetic quantities of fluoride can impact remineralization properties of
      commercially available tooth whitening gels without altering whitening
      properties.

PMID- 16911424
TI  - Accuracy of LED and halogen radiometers using different light sources.
AB  - PURPOSE: To determine the accuracy of commercially available, handheld light
      emitting diode (LED) and halogen-based radiometers using LED and quartz-tungsten
      halogen (QTH) curing lights with light guides of various diameters. METHODS: The
      irradiance of an LED curing light (L.E. Demetron 1, SDS/Kerr, Orange, CA, USA)
      and a QTH curing light (Optilux 501, SDS/Kerr) were measured using multiple units
      of an LED (Demetron L.E.D. Radiometer, SDS/Kerr) and a halogen radiometer
      (Demetron 100, SDS/Kerr) and compared with each other and to a laboratory-grade
      power meter (control). Measurements were made using five light guides with distal
      light guide diameters of 4, 7, 8, 10, and 12.5 mm. For each light guide, five
      readings were made with each of three radiometers of each radiometer type. Data
      were analyzed with two-way analysis of variance/Tukey; alpha = 0.05. RESULTS: In
      general, both handheld radiometer types exhibited significantly different
      irradiance readings compared with the control meter. Additionally, readings
      between radiometer types were found to differ slightly, but were correlated. In
      general, the LED radiometer provided slightly lower irradiance readings than the
      halogen radiometer, irrespective of light source. With both types of handheld
      radiometers, the use of the larger-diameter light guides tended to overestimate
      the irradiance values as seen in the control, while smaller-diameter light guides
      tended to underestimate. CLINICAL SIGNIFICANCE: The evaluated LED or halogen
      handheld radiometers may be used interchangeably to determine the irradiance of
      both LED and QTH visible-light-curing units. Measured differences between the two
      radiometer types were small and probably not clinically significant. However, the
      diameter of light guides may affect the accuracy of the radiometers, with larger
      diameter light guides overestimating and smaller-diameter guides underestimating
      the irradiance value measured by the control instrument.

PMID- 16911426
TI  - Critical Appraisal: At-home bleaching: pulpal effects and tooth sensitivity
      issues, part I.

PMID- 16911427
TI  - Halitosis.

PMID- 16911428
TI  - Editorial: mini special issue on cash transfers.

PMID- 16911429
TI  - Implementing cash for work programmes in post-tsunami Aceh: experiences and
      lessons learned.
AB  - Cash for work (CFW) programmes are utilised in various disaster and emergency
      contexts and were a prominent component of the tsunami response in Aceh province,
      Indonesia. This paper describes Mercy Corps' CFW programme, discusses CFW
      implementation experiences and provides key recommendations for similar
      programmes in future emergencies. For the majority of CFW participants and their
      households, CFW was the only source of household income and 93 per cent of
      household incomes were attributable to it. The CFW programme empowered displaced
      populations to return to their communities; 91 per cent of participants indicated
      that CFW facilitated their return. Other reported psychosocial benefits included
      providing productive activities and giving communities an opportunity to work
      together. Mercy Corps' experience in Aceh demonstrates that cash disbursements
      can be safely delivered in a widespread manner in emergencies, and that when
      implemented on a short-term basis, can have positive impacts at the individual
      and community level.

PMID- 16911430
TI  - Cash-based interventions: lessons from southern Somalia.
AB  - Commodity distributions, the predominant relief response, are subject to growing
      criticism, while donors and humanitarian actors are increasingly viewing cash
      based interventions as a viable alternative. This paper aims to contribute to the
      current debate on cash-based interventions by drawing on the experience of Action
      Contre la Faim in southern Somalia, where it has implemented cash for work
      programmes since 2004. The authors conclude that cash-based interventions are a
      feasible option in complex emergencies as well as in highly insecure environments
      as long as appropriate modalities are employed and objectives are clearly set in
      accordance with the needs and the context. Cash as a relief response offers wide
      reaching possibilities for the future from both the perspective of the
      donor/agency and the standpoint of the beneficiary. It enables the beneficiaries
      to take control of the relief themselves and to adapt it to their individual
      requirements in a timely manner.

PMID- 16911431
TI  - Does money work? Cash transfers to ex-combatants in disarmament, demobilisation
      and reintegration processes.
AB  - This paper analyses the relevance and potential of cash transfers as part of the
      disarmament, demobilisation and reintegration (DDR) assistance packages provided
      to ex-combatants in transitions from war to peace. To this end, a theoretical
      framework is established that permits the identification of the advantages and
      disadvantages of using cash in DDR. Subsequently, an empirical analysis is
      carried out to compare selected theoretical assumptions on the use of cash with
      the reality of lessons learned from recent experience in Sierra Leone and other
      African countries. The study shows that some theoretical drawbacks commonly
      associated with the use of cash in DDR processes may indeed bear out in practice.
      At the same time, though, the paper argues that the utility of cash transfers in
      DDR is affected by a variety of factors that go far beyond the simple choice of
      employing cash, most notably decisions on payment location, eligibility criteria
      and targeting.

PMID- 16911432
TI  - Tsunami mortality and displacement in Aceh province, Indonesia.
AB  - A survey of 388 Indonesian households displaced by the December 2004 tsunami was
      conducted in Aceh province in February 2005. Of tsunami-displaced households in
      Aceh Barat and Nagan Raya districts, 61.8 per cent reported one or more family
      members as dead or missing due to the tsunami, with an overall mortality rate of
      13.9 per cent (95% confidence interval (CI): 12.4-15.4). Risk of death was
      greatest in the youngest and oldest age groups, and among females. Overall, 36
      per cent of tsunami-displaced households indicated an intention to return to
      their original community within three months, and displaced households residing
      in host communities were 2.2 (95% CI: 1.2-2.8) times more likely to state an
      intention to return to their original villages or another community as those
      residing in camps. The tsunami recovery effort should focus on strategies that
      facilitate either prompt return or permanent, voluntary relocation for those
      displaced.

PMID- 16911433
TI  - Examining the CDCynergy Event Assessment Tool: an investigation of the anthrax
      crisis in Boca Raton, Florida.
AB  - This paper examines the dependability of the Event Assessment Tool over time. The
      latter is part of a CD-ROM--Emergency Risk Communication CDCynergy--distributed
      primarily to public information officers in the United States by the Centers for
      Disease Control and Prevention. The Event Assessment Tool is designed to aid
      emergency professionals in identifying the magnitude of a crisis event and to
      suggest appropriate actions to confront such a situation. Applied twice during
      the 2001 anthrax bioterrorism crisis in Boca Raton, Florida, the tool functioned
      in a binary manner by first indicating a moderate crisis level (on 4 October) and
      then four days later (on 8 October) a highly intense crisis, suggesting that it
      is time sensitive. This anthrax event provides an opportunity for crisis and
      disaster managers to understand the dynamic nature of crises. Rapid changes
      during these types of events suggest that any metric used to predict intensity
      must account for this variability. Additional limitations and implications of the
      tool are discussed.

PMID- 16911434
TI  - Are rapid population estimates accurate? A field trial of two different
      assessment methods.
AB  - Emergencies resulting in large-scale displacement often lead to populations
      resettling in areas where basic health services and sanitation are unavailable.
      To plan relief-related activities quickly, rapid population size estimates are
      needed. The currently recommended Quadrat method estimates total population by
      extrapolating the average population size living in square blocks of known area
      to the total site surface. An alternative approach, the T-Square, provides a
      population estimate based on analysis of the spatial distribution of housing
      units taken throughout a site. We field tested both methods and validated the
      results against a census in Esturro Bairro, Beira, Mozambique. Compared to the
      census (population: 9,479), the T-Square yielded a better population estimate
      (9,523) than the Quadrat method (7,681; 95% confidence interval: 6,160-9,201),
      but was more difficult for field survey teams to implement. Although applicable
      only to similar sites, several general conclusions can be drawn for emergency
      planning.

PMID- 16911436
TI  - Six-month-old infants use analog magnitudes to represent duration.
AB  - While many studies have investigated duration discrimination in human adults and
      in nonhuman animals, few have investigated this ability in infants. Here, we
      report findings that 6-month-old infants are able to discriminate brief
      durations, and, as with other animal species, their discrimination function is
      characterized by Weber's Law: proportionate difference rather than absolute
      difference between stimuli determined successful discrimination. Importantly,
      paralleling results found with nonhuman animals, the Weber function that we found
      for infants' discrimination of time is the same as that found for their
      discrimination of number. Infants discriminated durations of an audiovisual event
      differing by a 1:2 ratio, but not those differing by a 2:3 ratio, over a range of
      durations. This suggests that (a) in human as in nonhuman animals, the same
      mental mechanism may underlie the ability to measure duration as to represent
      number, and (b) we may share this mental mechanism with other animal species.

PMID- 16911437
TI  - Interrupting infants' persisting object representations: an object-based limit?
AB  - Making sense of the visual world requires keeping track of objects as the same
      persisting individuals over time and occlusion. Here we implement a new paradigm
      using 10-month-old infants to explore the processes and representations that
      support this ability in two ways. First, we demonstrate that persisting object
      representations can be maintained over brief interruptions from additional
      independent events - just as a memory of a traffic scene may be maintained
      through a brief glance in the rearview mirror. Second, we demonstrate that this
      ability is nevertheless subject to an object-based limit: if an interrupting
      event involves enough objects (carefully controlling for overall salience), then
      it will impair the maintenance of other persisting object representations even
      though it is an independent event. These experiments demonstrate how object
      representations can be studied via their 'interruptibility', and the results are
      consistent with the idea that infants' persisting object representations are
      constructed and maintained by capacity-limited mid-level 'object-files'.

PMID- 16911438
TI  - Becoming literate in different languages: similar problems, different solutions.
AB  - The teaching of reading in different languages should be informed by an effective
      evidence base. Although most children will eventually become competent, indeed
      skilled, readers of their languages, the pre-reading (e.g. phonological
      awareness) and language skills that they bring to school may differ in systematic
      ways for different language environments. A thorough understanding of potential
      differences is required if literacy teaching is to be optimized in different
      languages. Here we propose a theoretical framework based on a psycholinguistic
      grain size approach to guide the collection of evidence in different countries.
      We argue that the development of reading depends on children's phonological
      awareness in all languages studied to date. However, we propose that because
      languages vary in the consistency with which phonology is represented in
      orthography, there are developmental differences in the grain size of lexical
      representations, and accompanying differences in developmental reading strategies
      across orthographies.

PMID- 16911439
TI  - Learning to read in Turkish.

PMID- 16911440
TI  - Becoming literate in Hebrew: the grain size hypothesis and semitic orthographic
      systems.

PMID- 16911441
TI  - Units and routes of reading in Dutch.

PMID- 16911442
TI  - On the advantage of 'shallow' orthographies: number and grain size of the
      orthographic units or consistency per se?

PMID- 16911443
TI  - Refining the psycholinguistic grain size theory: effects of phonotactics and word
      formation on the availability of phonemes to preliterate children.

PMID- 16911444
TI  - Don't neglect reading fluency!

PMID- 16911445
TI  - A neurocognitive overview of reading acquisition and dyslexia across languages.

PMID- 16911447
TI  - Development of multisensory spatial integration and perception in humans.
AB  - Previous studies have shown that adults respond faster and more reliably to
      bimodal compared to unimodal localization cues. The current study investigated
      for the first time the development of audiovisual (A-V) integration in spatial
      localization behavior in infants between 1 and 10 months of age. We observed
      infants' head and eye movements in response to auditory, visual, or both kinds of
      stimuli presented either 25 degrees or 45 degrees to the right or left of
      midline. Infants under 8 months of age intermittently showed response latencies
      significantly faster toward audiovisual targets than toward either auditory or
      visual targets alone They did so, however, without exhibiting a reliable
      violation of the Race Model, suggesting that probability summation alone could
      explain the faster bimodal response. In contrast, infants between 8 and 10 months
      of age exhibited bimodal response latencies significantly faster than unimodal
      latencies for both eccentricity conditions and their latencies violated the Race
      Model at 25 degrees eccentricity. In addition to this main finding, we found age
      dependent eccentricity and modality effects on response latencies. Together,
      these findings suggest that audiovisual integration emerges late in the first
      year of life and are consistent with neurophysiological findings from
      multisensory sites in the superior colliculus of infant monkeys showing that
      multisensory enhancement of responsiveness is not present at birth but emerges
      later in life.

PMID- 16911448
TI  - Eye remember you two: gaze direction modulates face recognition in a
      developmental study.
AB  - The effects of gaze direction on memory for faces were studied in children from
      three different age groups (6-7, 8-9, and 10-11 years old) using a computerized
      version of a task devised by Hood, Macrae, Cole-Davies and Dias (2003).
      Participants were presented with a sequence of faces in an encoding phase, and
      were then required to judge which faces they had previously encountered in a
      surprise two-alternative forced-choice recognition test. In one condition,
      stimulus eye gaze was either direct or deviated at the viewing phase, and eyes
      were closed at the test phase. In another condition, stimulus eyes were closed at
      the viewing phase, with either direct or deviated gaze at the test phase.
      Modulation of gaze direction affected hit rates, with participants demonstrating
      greater accuracy for direct gaze targets compared to deviated gaze targets in
      both conditions. Reaction times (RT) to correctly recognized stimuli were faster
      for direct gaze stimuli at the viewing phase, but not at the test phase. The age
      group of participants differentially affected these measures: there was a greater
      hit rate advantage for direct gaze stimuli in older children, although RTs were
      less affected by age. These findings suggest that while the facilitation of face
      recognition by gaze direction is robust across encoding and recognition stages,
      the efficiency of the process is affected by the stage at which gaze is
      modulated.

PMID- 16911449
TI  - Error-related electrocortical responses in 10-year-old children and young adults.
AB  - Recent anatomical and electrophysiological evidence suggests that the anterior
      cingulate cortex (ACC) is relatively late to mature. This brain region appears to
      be critical for monitoring, evaluating, and adjusting ongoing behaviors. This
      monitoring elicits characteristic ERP components including the error-related
      negativity (ERN), error positivity (Pe) and correct-related negativity (CRN),
      with the ERN clearly relating to activation of the ACC; however, little attention
      has been paid to the examination of these ERP components in children. The present
      study examined developmental differences in the ERN, Pe, and CRN in normal 10
      year-old children and young adults in a standard visual flanker task. We found
      that children had smaller ERNs than adults, with no between-group differences on
      the Pe, and some ambiguity concerning the CRN. Results provide
      electrophysiological support either for late maturation of the ACC or late
      involvement of the ACC in response monitoring. Results also suggest that there is
      some functional independence of response-monitoring ERP components. Error-related
      ERPs may be a useful tool in studying the development of this brain region and
      its role in behavior in normal and atypical development.

PMID- 16911450
TI  - A new method for calibrating perceptual salience across dimensions in infants:
      the case of color vs. luminance.
AB  - We report a new method for calibrating differences in perceptual salience across
      feature dimensions, in infants. The problem of inter-dimensional salience arises
      in many areas of infant studies, but a general method for addressing the problem
      has not previously been described. Our method is based on a preferential looking
      paradigm, adapted to determine the relative salience of two stimuli. We report
      here on the case of stimuli differing in color and luminance, though the method
      has wider potential. We were able to determine on a psychophysical curve the
      point at which a color contrast was equally salient to infants as a given
      luminance contrast. We then used these calibrated, 'iso-salient' stimuli in an
      object memory study. Results showed that 6.5-month-old infants noticed a color,
      but not a luminance, change while tracking an occluded object. Our method should
      have numerous applications in the study of bottom-up effects on infant attention
      and visual working memory.

PMID- 16911451
TI  - The development of change detection.
AB  - Changes to a scene often go unnoticed if the objects of the change are
      unattended, making change detection an index of where attention is focused during
      scene perception. We measured change detection in school-age children and young
      adults by repeatedly alternating two versions of an image. To provide an age-fair
      assessment we used a bimanual choice rather than open-ended verbal responses. The
      difference in detection speed and accuracy between 50-ms versus 250-ms blank
      screens between views indexed change detection in short-term visual memory
      independent of sensory and response processes. Younger children were
      significantly less efficient than older participants, especially when an object
      changed color or had a part deleted. Changes in object orientation were detected
      more readily. These results point to important differences in the perceptual
      reality of younger and older children.

PMID- 16911452
TI  - A longitudinal behavioral genetic analysis of task persistence.
AB  - Change in task persistence was assessed in two annual assessments using
      teachers', testers', and observers' ratings. Participants included 79 monozygotic
      and 116 same-sex dizygotic twin pairs who were in Kindergarten or 1st grade (4.3
      to 7.9 years old) at the initial assessment. Task persistence was widely
      distributed and higher among older children and girls. Overall, there was modest
      growth in persistence over time, and moderate stability of individual
      differences. Most of the stability was accounted for by genetic influences,
      whereas most of the change was accounted for by nonshared environment, including
      an association with observed differential maternal warm supportive behavior.

PMID- 16911453
TI  - Young children's use of a delayed video representation to solve a retrieval
      problem pertaining to self.
AB  - The experiments reported here were concerned with the development of delayed self
      recognition. Children were videotaped playing a game and were marked covertly
      with a sticker on their forehead while doing so. The findings, of both a cross
      sectional sample and a prospective longitudinal one, revealed that 3- but not 2.5
      year-old children reached to remove this sticker reliably during video playback
      only after they had been trained to use the video to guide their search for an
      object that was not directly visible to the unaided eye. It appears that by 3
      years of age children understand that their briefly delayed self video
      representation is related to their present self. In contrast, while 2.5-year-olds
      can use delayed video information to locate objects in space that cannot be seen
      by the unaided eye, they cannot use this type of information to locate an object
      that pertains to a part of self that is not directly visible, such as a sticker
      on one's hair. The findings are discussed in terms of the emergence of an
      extended sense of self.

PMID- 16911454
TI  - Apes' and children's understanding of cooperative and competitive motives in a
      communicative situation.
AB  - Chimpanzees (Pan troglodytes) and bonobos (Pan paniscus) (Study 1) and 18- and 24
      month-old human children (Study 2) participated in a novel communicative task. A
      human experimenter (E) hid food or a toy in one of two opaque containers before
      gesturing towards the reward's location in one of two ways. In the Informing
      condition, she attempted to help the subject find the hidden object by simply
      pointing to the correct container. In the Prohibiting condition, E held out her
      arm toward the correct container (palm out) and told the subject firmly 'Don't
      take this one.' As in previous studies, the apes were at chance in the Informing
      condition. However, they were above chance in the new Prohibiting condition.
      Human 18-month-olds showed this same pattern of results, whereas 24-month-olds
      showed the opposite pattern: they were better in the Informing condition than in
      the Prohibiting condition. In our interpretation, success in the Prohibiting
      condition requires subjects to understand E's goal toward them and their
      behavior, and then to make an inference (she would only prohibit if there were
      something good in there). Success in the Informing condition requires subjects to
      understand a cooperative communicative motive - which apparently apes and young
      infants find difficult.

PMID- 16911455
TI  - Developmental changes in perceptions of attractiveness: a role of experience?
AB  - In three experiments, we traced the development of the adult pattern of judgments
      of attractiveness for faces that have been altered to have internal features in
      low, average, or high positions. Twelve-year-olds and adults demonstrated
      identical patterns of results: they rated faces with features in an average
      location as significantly more attractive than faces with either low or high
      features. Although both 4-year-olds and 9-year-olds rated faces with high
      features as least attractive, unlike adults and 12-year-olds, they rated faces
      with low and average features as equally attractive. Three-year-olds with high
      levels of peer interaction, but not those with low levels of peer interaction,
      chose faces with low features as significantly more attractive than those with
      high-placed features, possibly as a result of their increased experience with the
      proportions of the faces of peers. Overall, the pattern of results is consistent
      with the hypothesis that experience influences perceptions of attractiveness,
      with the proportions of the faces participants see in their everyday lives
      influencing their perceptions of attractiveness.

PMID- 16911456
TI  - Quality of life in hepatitis C.
AB  - A number of different studies have shown a clear reduction in the quality of life
      of hepatitis C virus (HCV)-related liver-disease patients. Quality of life can be
      assessed by means of both generic and specific instruments, depending on the aim
      of the study and the population being studied. The application of a specific
      instrument to patients with liver diseases provides a broader assessment of
      different parameters related to hepatic disorders. In hepatitis C, alterations
      such as the stigma of liver disease, concerns about the disease and symptoms of
      the disease could be demonstrated with this type of instrument. The impact of the
      diagnosis of hepatitis C, a potentially serious disease, and the presence of
      comorbidities such as alcohol and drugs may lead to lower quality of life.
      Longitudinal studies have proved that, following diagnosis, the stigma of liver
      disease becomes more apparent over time. Women report worse quality of life than
      men, supporting that gender differences in hepatitis are also important when
      assessing quality of life. Alterations in the quality of life of patients
      submitted to treatment are mainly related to the somatic side effects of
      Interferon and Ribavirin and are most noticeable in the first weeks of therapy.
      Early improvement in the quality of life of patients who become HCV-RNA negative
      suggests that the virus itself plays a biological role. There is no doubt that
      liver transplantation leads to an improvement in quality of life. Nevertheless, a
      major concern is the relapse of HCV, with the associated lower quality of life.

PMID- 16911457
TI  - Do young hepatocellular carcinoma patients have worse prognosis? The paradox of
      age as a prognostic factor in the survival of hepatocellular carcinoma patients.
AB  - BACKGROUND/AIMS: Our previous study showed that male hepatocellular carcinoma
      (HCC) patients below 40 years of age had the worst survival in the initial
      several years, but had the best prognosis thereafter. Thus, it seems that age has
      a paradoxical influence on the prognosis. To further clarify the issue of age on
      HCC prognosis, we initiated this study. METHODS: A total of 11,312 HCC cases from
      seven medical centers from 1986 to 2002 were included. We analyzed the 1-year
      survival and survival after 1 year. RESULTS: Male gender, age younger than 40
      years old and hepatitis B virus (HBV) were associated with worse 1-year survival.
      In contrast, male gender, age younger than 40 years old and HBV were associated
      with better survival after 1 year. Higher percentage of the young HCC patients
      had a tumor size larger than 3 cm. 83.7% of HCC patients below 40 years of age
      were male and 89.8% of them were HBV carriers. CONCLUSIONS: If we encountered a
      young HCC patient, the patient will probably be a male HBV carrier. He would
      probably have larger tumor and is more likely to expire within 1 year than the
      older HCC patients. However, if the young HCC patient can survive for more than 1
      year, he would probably have better survival in the following years than the
      older patients.

PMID- 16911458
TI  - Decreased expressions of hepsin in human hepatocellular carcinomas.
AB  - BACKGROUND/AIMS: Hepsin is a type II transmembrane protein predominantly
      expressed in the liver and has been implicated in participation in blood
      coagulation pathway and epithelial carcinogenesis. The aim of this current study
      is to investigate the role of hepsin in hepatocarcinogenesis. METHODS:
      Quantitative real-time RT-PCR was used to investigate the expression levels of
      hepsin in a total of 50 paired hepatocellular carcinomas (HCCs) and the
      corresponding non-tumor liver tissues. Hepsin was transfected to the hepsin-non
      expressing SK-HEP-1 cells to study the change of cell proliferation. RESULTS: In
      62% (31/50) patients, the expression levels of hepsin in non-tumor liver tissues
      are at least twofold higher than those in the corresponding HCC tissues. Positive
      hepatitis B surface antigen was more often detected in patients with hepsin
      underexpressed in the HCC tissues (74.2% vs. 31.6%, P=0.007). Patients with
      hepsin underexpressed in the HCC tissues survived shorter time than those without
      hepsin underexpression in the HCC tissues. The cell proliferation and for a
      colony formation of SK-HEP-1 HCC cells were inhibited by hepsin. CONCLUSIONS:
      Most HCC patients had hepsin underexpressed in the HCC tissues. These patients
      survived for a shorter time compared with those without hepsin underexpression in
      the HCC tissues. Hepsin expression could inhibit cell proliferation and colony
      formation of HCC cells.

PMID- 16911459
TI  - Value of fusing PET plus CT images in hepatocellular carcinoma and combined
      hepatocellular and cholangiocarcinoma patients with extrahepatic metastases:
      preliminary findings.
AB  - BACKGROUND/AIMS: This study aimed to evaluate the usefulness of (18)F-fluoro-2
      deoxy-d-glucose positron emission tomography (PET) and PET plus computed
      tomography (CT) fusion images for the detection of extrahepatic metastases of
      hepatocellular carcinoma (HCC) and combined hepatocellular and cholangiocarcinoma
      (combined HCC/CC). METHODS: Twenty-one patients with HCC and combined HCC/CC were
      enrolled in the study from December 2004 to February 2005. In all patients, PET
      and CT of the chest to pelvis region were performed. The sensitivity of PET plus
      CT fusion images was compared with the sensitivity of PET, CT, and bone
      scintigraphy. RESULTS: In 14 patients, a total of 58 extrahepatic metastases were
      diagnosed. The detection rate of PET plus CT fusion images, PET, CT, and bone
      scintigraphy was 98.2% (57 of 58 metastases), 89.6% (52 of 58 metastases), 91.2%
      (52 of 57 metastases), and 68.7% (11 of 16 bone metastases), respectively. No
      extrahepatic metastases were detected in the other seven patients. The detection
      rate of PET was 10/18 (55.6%) for intrahepatic lesions of HCC and combined
      HCC/CC. CONCLUSIONS: The fusion of PET plus CT images is useful in detecting
      extrahepatic metastases in HCC and combined HCC/CC patients.

PMID- 16911460
TI  - Clinical features of hepatitis C virus-related hepatocellular carcinoma and their
      association with alpha-fetoprotein and protein induced by vitamin K absence or
      antagonist-II.
AB  - PURPOSE: We investigated the differences in clinical features between alpha
      fetoprotein (AFP)-predominant hepatocellular carcinoma (HCC) and protein induced
      by vitamin K absence or antagonist-II (PIVKA-II)-predominant HCC, especially
      regarding host factors thought to contribute to hepatocarcinogenesis in chronic
      hepatitis C virus (HCV) infection. METHODS: HCV-related HCC patients (n=306) were
      divided into four groups according to median AFP (48.1 ng/ml) and PIVKA-II (60
      mAU/ml). Host factors, tumor factors, survival, and risk factors affecting
      survival were compared. RESULTS: Aspartate aminotransferase (AST; IU/L), alanine
      aminotransferase (ALT; IU/L), and platelet count (x 10(4)/ml) were, respectively,
      81, 67, and 8.2 in AFP-predominant HCC (group A; n=66) vs. 50, 42, and 11.4 in
      PIVKA-II-predominant HCC (group P; n=52). Tumor sizes (mm) in groups A and P were
      20 and 37, respectively. Significant differences were evident. Survival was
      identical between the two groups. Factors affecting survival were total
      bilirubin, portal tumor thrombus and number of nodule in group A, and albumin and
      tumor distribution in group P. CONCLUSIONS: PIVKA-II-predominant HCC had a milder
      hepatitis and a better-preserved platelet count compared with AFP-predominant
      HCC. Considering the strong relation between hepatocarcinogenesis and hepatic
      inflammation with chronic HCV infection, these differences indicate that
      hepatocarcinogenic mechanisms in PIVKA-II-predominant HCC may differ from those
      in AFP-predominant HCC.

PMID- 16911461
TI  - Hepatitis B virus genotypes, precore and core promoter variants among
      predominantly Asian patients with chronic HBV infection in a Canadian center.
AB  - BACKGROUND AND AIMS: The epidemiology of hepatitis B virus (HBV) infection in
      North America may be changing as a result of immigration from endemic countries.
      The purpose of this study was to determine the prevalence of HBV genotypes,
      precore (PC) and core promoter (CP) variants, and the proportion of patients
      meeting treatment criteria for HBV. METHODS: A cross-sectional study of
      consecutive HBV patients attending a Canadian tertiary liver center was
      conducted. HBV DNA was quantified by polymerase chain reaction assay. HBV
      genotypes and variants were determined using a line probe assay. RESULTS: Two
      hundred and seventy-two patients were enrolled; 200 were not receiving treatment
      at enrollment, of whom 116 were men and 84 women with a mean age 42+/-14 years.
      Among this group, 177 (88%) patients were Asian and 19 (10%) were Caucasian and
      69 (35%) patients were hepatitis B e antigen (HBeAg) positive. Genotypes B and C
      were found in 42% and 50% untreated patients, respectively; while CP and PC were
      detected in 52% and 43% patients, respectively. Approximately 20% patients not
      receiving treatment (29% HBeAg positive, 14% HBeAg negative) met AASLD guidelines
      for antiviral therapy. If lower cutoff values for alanine aminotransferase and
      HBV DNA levels were used, 49% patients would qualify for treatment. CONCLUSIONS:
      The vast majority of patients at a Canadian tertiary referral center were Asian.
      Virological and clinical characteristics of these patients reflect their country
      of origin. Our findings highlight the need to monitor the changing patterns of
      HBV infection in countries with large immigrant populations.

PMID- 16911462
TI  - Treatment of chronic hepatitis delta with pegylated interferon-alpha2b.
AB  - BACKGROUND/AIMS: Chronic hepatitis D is difficult to treat. The present pilot
      study investigated the efficacy and tolerability of pegylated (PEG)-interferon
      (IFN)-alpha2b in chronic hepatitis D. PATIENTS AND METHODS: Twelve patients with
      chronic hepatitis D were prospectively treated with 1.5 microg/kg PEG-IFN-alpha2b
      for 48 weeks and followed for 24 weeks. Sustained response (SR) was defined as
      undetectable hepatitis delta virus (HDV) RNA by reverse transcriptase-polymerase
      chain reaction and normalization of alanine aminotransferase (ALT) at 6 months
      after treatment. Investigations included HDV RNA kinetics, determination of
      hepatitis B virus (HBV) and HDV genotypes and histological evaluation. RESULTS:
      An SR was achieved in two out of 12 of patients (17%). The negative predictive
      value of a less than 3 log HDV RNA decrease at month 6 was 100%. The positive
      predictive value of a more than 3 log HDV RNA decrease at month 6 was 67%. A
      marked ALT reduction at the end of treatment was observed in responders and
      nonresponders. Ishak histological score was comparable at baseline and
      significantly improved in responders compared with nonresponders at the end of
      follow-up (13.5 vs. 8.0; P<0.02). CONCLUSION: The present study indicates that
      PEG-IFN-alpha2b is a promising treatment option in chronic hepatitis D.
      Nonresponders could be identified by a less than 3 log decrease of HDV RNA at 6
      months of treatment.

PMID- 16911463
TI  - Antiviral treatment withdrawal in viremic HCV-positive liver transplant patients:
      impact on viral loads, allograft function and morphology.
AB  - BACKGROUND: The aim of this study was to evaluate the clinical long-term
      consequences of antiviral treatment discontinuation in viremic hepatitis C virus
      (HCV)-positive liver transplant recipients. METHODS: Twenty-five HCV-positive
      patients after liver transplantation were included in this study. After
      diagnosing recurrent hepatitis C, a combination therapy with interferon-alpha2b
      and ribavirin for a minimum of 12 months was initiated. Viremia levels and
      allograft function were monitored continuously. Allograft biopsies were performed
      yearly, analyzing grading of inflammation and staging of fibrosis. RESULTS: HCV
      recurrence rate was 100%. Up to 114 months post-transplantation, sustained
      virological response rate was 64%. Treatment discontinuation in virological
      nonresponders led subsequently to a significant increase of viral loads and
      deterioration of allograft function (P<0.05) within 1 month. In three patients, a
      fibrosing cholestatic syndrome developed, resulting in one patient death.
      Antiviral retherapy was maintained for a mean of 33 months, leading to a
      significant decline of aminotransferases (P<0.05) as well as decreasing serum
      levels of bilirubin and HCV-RNA within 6 months. In addition, development of
      severe allograft fibrosis was prevented despite persistent viral loads.
      CONCLUSION: Our study suggests that antiviral treatment withdrawal carries the
      risk of severe disease progression in persistently viremic HCV-positive liver
      transplant patients.

PMID- 16911464
TI  - Potential role of hepatic progenitor cells expression in cases of chronic
      hepatitis C and their relation to response to therapy: a clinicopathologic study.
AB  - BACKGROUND: This study investigates the correlation of hepatic progenitor cells
      (HPC) expression with treatment response in patients with chronic hepatitis C.
      DESIGN: The study comprised 77 liver biopsies with chronic hepatitis C (HCV). All
      patients were PCR-HCV (+) and received antiviral therapy with interferon or
      pegylated interferon alpha-2b and ribavirin. Twenty-nine patients were assigned
      as responders (group A), 29 as nonresponders (group B) and 19 as relapsers (group
      C). Ten normal liver biopsies were used as controls. Liver paraffin sections were
      subjected (a) to immunohistochemistry using antibodies for cytokeratins 19 (CK19)
      and 7 (CK7), alpha-fetoprotein (AFP), leukocyte common antigen (LCA) and CD34
      antigen (b) to in situ hybridization for AFP mRNA and (c) to
      immunohistochemistry+in situ hybridization. Results were expressed as % of
      positive cells following morphometric analysis. RESULTS: HPC expression was
      present in all 87 specimens. In the control biopsies, rare HPC were detected. In
      the CH cases and according to AFP mRNA expression, the grade for % HPC expression
      was: group B: 53.2+/-2.6> group C: 48.37+/-1.8> group A: 31.4+/-1.6 (group A vs B
      P<0.01, group A vs C P<0.01, group B vs C P>0.05. Double stain revealed that HPC
      coexpressed CK19/AFP mRNA, CK7/AFP mRNa and AFP protein/AFP mRNA. HPC-percentages
      were directly correlated with total HAI score (P<0.01), fibrosis stage (P<0.01),
      and transaminase values (P<0.05). CONCLUSIONS: This study demonstrates that in
      cases of chronic hepatitis C, the significant association of HPC expression with
      the severity of disease and more specifically with the response to treatment
      implies that HPC development and proliferation may provide additional prognostic
      information and predict prognosis in such cases.

PMID- 16911465
TI  - Influence of Helicobacter pylori infection on iron accumulation in hepatitis C.
AB  - GOAL: Iron may play a role in the pathogenesis of chronic hepatitis C.
      Helicobacter pylori (Hp) infection was recently associated with iron-deficiency
      anemia. We examined the influence of Hp infection on hepatic iron accumulation in
      hepatitis C. METHODS: Ninety-five hepatitis C virus (HCV)-RNA-positive patients,
      including 60 chronic hepatitis, 17 cirrhosis and 18 hepatocellular carcinoma as
      well as 95 age- and sex-matched normal subjects without HCV infection as control,
      were studied. Liver biopsies were also obtained from 44 HCV-infected patients.
      Serum Hp antibodies were measured by an enzyme-linked immunosorbent assay and
      clinical data, including iron parameters and histological findings, were compared
      between Hp-positive and -negative HCV-infected patients. RESULTS: The percentage
      of serum Hp antibodies was lower in HCV-infected patients than in controls (52/95
      (54.7%) vs. 68/95 (71.6%); P<0.05). HCV-infected patients had higher serum
      ferritin levels than controls (120 [2.8-1700] vs. 58 [2.2-420] ng/ml; P<0.0001).
      In HCV-infected patients, the serum ferritin levels (medians and [ranges]) in Hp
      positive patients were significantly lower than those of Hp-negative patients (99
      [8.5-770] vs. 150 [2.8-1700] ng/ml; P<0.05). The grades of hepatic iron deposit
      in Hp-positive patients were significantly lower than those in Hp-negative
      patients (P<0.01). CONCLUSIONS: Hp infection may at least partly affect hepatic
      iron accumulation in HCV-related liver diseases.

PMID- 16911466
TI  - Prognostic factors for patients with cirrhosis and kidney dysfunction in the era
      of MELD: results of a prospective study.
AB  - BACKGROUND/AIM: Hepatorenal syndrome (HRS) is associated with a poor prognosis.
      The incidence and prognostic impact of kidney dysfunction due to other causes in
      cirrhotic patients are less well known. The current study prospectively evaluated
      the incidence and the prognostic relevance of different etiologies of kidney
      failure in cirrhotic patients. METHODS: Eighty-eight consecutive patients with
      cirrhosis and serum creatinine > or =1.5 mg/dl were enrolled. The etiologies of
      kidney dysfunction were analyzed, and prognostic factors including Model for End
      Stage Liver Disease (MELD) score were evaluated in a multivariate Cox model.
      RESULTS: HRS was present in 35 (40%) patients (15 HRS 1, 20 HRS 2), followed by
      renal parenchymal disease (23%), drug-induced kidney dysfunction (19%) and
      prerenal failure due to bleeding or infections (15%). HRS patients had a
      significantly higher MELD score and shorter survival. In addition to the MELD
      score, only HRS 1 was independently predictive for survival. HRS 2 patients had a
      similar outcome as patients with non-HRS kidney dysfunction. CONCLUSIONS: In
      patients with cirrhosis and renal failure, hepatorenal syndrome is associated
      with a worse prognosis than kidney dysfunction due to other conditions but only
      HRS type 1 has independent prognostic relevance in addition to the MELD score in
      these patients.

PMID- 16911467
TI  - The AST/ALT ratio as an indicator of cirrhosis in patients with PBC.
AB  - OBJECTIVES: A non-invasive, simple and non-expensive test to predict cirrhosis
      would be highly desirable. The aspartate aminotransferase/alanine
      aminotransferase (AST/ALT) ratio has been proven to be such an indicator of
      cirrhosis in alcoholic liver disease, hepatitis C. AIM: To test whether the
      AST/ALT ratio is a marker of cirrhosis also in patients with primary biliary
      cirrhosis (PBC). METHODS: The study consisted of 160 patients. In 126 patients,
      we had clinical and laboratory data at the time of diagnosis and follow-up with
      outcome: liver-related death, liver transplantation and survival. In 121
      patients, we had laboratory data and liver histology. RESULTS: We found that the
      AST/ALT ratio was significantly higher in cirrhotic patients than in non
      cirrhotic patients. A high AST/ALT ratio was significantly associated with
      esophageal varices and ascites. In a multivariate analysis, bilirubin and ALP
      were predictors of poor prognosis. CONCLUSION: The AST/ALT ratio seems to be of
      clinical value as a hint to the diagnosis of cirrhosis in patients with PBC but
      not as a prognostic factor.

PMID- 16911468
TI  - Demonstration of PDC-E1 subunits as major antigens in the complement-fixing
      fraction M4 and re-evaluation of PDC-E1-specific antibodies in PBC patients.
AB  - BACKGROUND: Primary biliary cirrhosis (PBC) is characterized by the presence of
      antimitochondrial antibodies (AMA). Autoantibodies specific for the mitochondrial
      M4 antigen can be detected by a complement fixation test (CFT) but not by
      immunoblotting. The aim of this study was to elucidate the identity of the M4
      antigen. PATIENTS AND METHODS: M4 proteins were purified by affinity
      chromatography using IgG fractions of PBC marker sera being CFT positive (n=5) or
      negative (n=5) and identified by Western blotting, silver staining and sequence
      analysis. Further, a cohort of 57 PBC patients was tested for the reactivity to
      M4 and pyruvate dehydrogenase complex (PDC). RESULTS: Two AMA patterns of the
      marker sera were visualized: CFT-positive sera were defined as PDC-E2(+)/E1(+)
      and the CFT-negative sera as PDC-E2(+)/E1(-). The major proteins in the M4
      fraction could be related to the PDC-E1 subunits. A clear-cut association between
      anti-M4 reactivity in the CFT and the reactivity to both PDC subunits could also
      be documented in the cohort of 57 PBC patients showing anti-PDC-E1alpha and
      E1beta antibodies at a frequency of 74% and 67%. CONCLUSIONS: CFT reactivity
      against M4 antigens could be preferentially identified as a reaction against PDC
      E1. As PDC-E1 subunits as compared with PDC-E2 lack lipoyl-binding sites, they
      probably have to be considered as an independent and important target.

PMID- 16911469
TI  - Prevalence of primary non-alcoholic fatty liver disease in a population-based
      study and its association with biochemical and anthropometric measures.
AB  - BACKGROUND/AIMS: Only a few studies have assessed the epidemiology of non
      alcoholic fatty liver disease (NAFLD). The aim was to evaluate the prevalence of
      primary NAFLD in a population-based study in Israel and to determine independent
      risk factors. METHODS: A cross-sectional study of a subsample of the Israeli
      national health survey (n=352). Individuals with a known etiology for secondary
      NAFLD were excluded. Each participant underwent an abdominal ultrasound,
      biochemical tests and an anthropometric evaluation. RESULTS: Three hundred and
      twenty-six subjects (53.4% male, mean age 50.5+/-10.3 standard deviaton [SD]) met
      the inclusion criteria. The prevalence of primary NAFLD was 30% (25-35% 95%
      confidence intervals [CI]). NAFLD was more prevalent in men than women (38% vs.
      21%; P=0.001). Compared with ultrasonography, the sensitivity of serum alanine
      transaminase (ALT) for the diagnosis of primary NAFLD was 8.2%. Risk factors
      independently associated with NAFLD included male gender (odds ratios (OR)=2.8,
      95% CI 1.5-5.3), abdominal obesity (OR=2.9, 95% CI 1.3-6.4), homeostasis model
      assessment (OR=5.8, 95% CI 2.0-17.2), hyperinsulinemia (OR=2.3, 95% CI 1.2-4.3,
      P=0.01) and hypertriglyceridemia (OR=2.4, 95% CI 1.3-4.5). CONCLUSIONS: NAFLD is
      prevalent in the general Israeli population and closely related to the metabolic
      syndrome. The use of ALT as a marker for NAFLD seriously underestimates its
      prevalence.

PMID- 16911470
TI  - Non-invasive markers to predict the liver fibrosis in non-alcoholic fatty liver
      disease.
AB  - BACKGROUND/AIM: The aim of this study was to find a non-invasive marker, which
      could predict liver fibrosis without the need of liver biopsy in non-alcoholic
      steatohepatitis (NASH). PATIENTS/METHODS: Fifty patients were included. All
      patients had one or more conditions that characterize the metabolic syndrome and
      histological proven NASH. Hyaluronic acid (HA), leptin (LT) and laminin (LN) were
      determined from serum withdrawn at the day of biopsy. RESULTS: Patients were
      divided into two groups according to the histological findings. The first group
      consisted of 23 patients with NASH and fibrosis and the second group had 27
      patients with NASH, ballooned cells, without fibrosis. Subjects with NASH and
      fibrosis had statistically significantly higher HA and LN than those with NASH
      without fibrosis, P<0.001, respectively. In contrast, there was no statistically
      significant difference between the levels of serum LT in the two groups. The
      stage of liver fibrosis in the 23 patients of group 1 was related only to the
      values of hyaluronic acid (P<0.001) and not to the ones of LT and LN. CONCLUSION:
      Measurement of hyaluronic acid could be a predictive factor of the presence and
      stage of liver fibrosis in NASH. LN could be used to diagnose liver fibrosis but
      has no value in staging.

PMID- 16911471
TI  - Intrahepatic activation of caspases in human fulminant hepatic failure.
AB  - BACKGROUND/AIMS: Apoptosis has been implicated in the pathogenesis of fulminant
      hepatic failure (FHF) potentially involving caspases. Thus far, apoptosis in FHF
      has mainly been studied in animal models while human data are sparse. METHODS:
      Caspases-3, -8 and -9 activities and Fas expression were analyzed in correlation
      to TdT-mediated dUTP nick end labelling (TUNEL) positive apoptotic cells in
      livers of patients with FHF (n=26), chronic liver disease (CLD) (n=60) and normal
      controls (NC) (n=10). RESULTS: Numbers of TUNEL-positive cells were higher in FHF
      than in CLD and NC (P<0.001) correlating to the intrahepatic activities of
      caspase-3. The highest caspase-3 activities were found in fulminant hepatitis B,
      significantly surpassing those in FHF of any other etiology. In fulminant
      hepatitis B, caspase-9 activity was also higher than in controls, while caspase-8
      activation was not higher than in NC. Unlike caspase-3, caspases -8 and -9
      activities were not correlated to the numbers of TUNEL positive cells. Fas
      expression was also the highest in FHF but did not differ between hepatitis B
      virus-FHF and other FHF. CONCLUSIONS: Our data indicate differential activation
      of intrahepatic caspases in FHF depending on the underlying etiology. Massive
      activation of caspases in fulminant hepatitis B confirms a pivotal role of
      apoptotic pathways in the pathogenesis of human fulminant hepatitis B.

PMID- 16911472
TI  - Wash-out of the non-heart-beating donor liver: a matter of flush solution and
      temperature?
AB  - BACKGROUND AND AIMS: Ischemically damaged donor livers are prone to graft non
      function. This can in part be explained by a suboptimal wash-out during
      procurement. An enriched machine perfusion (MP) preservation solution for livers,
      named Polysol, was developed. The aim of this study was to investigate the type
      of flush solution, temperature and anticoagulant content on the wash-out of the
      non-heart-beating donor (NHBD) rat liver. METHODS: Rat livers were flushed after
      30 min warm ischemia. After excision, livers were reperfused at 37 degrees C,
      with analysis of damage and function, concerning (1) solutions (University of
      Wisconsin (UW), histidine-tryptophan-ketoglutarate (HTK) and Polysol); (2)
      temperature (4 degrees C, 18 degrees C and 37 degrees C); (3) addition of heparin
      and (4) wash-out followed by 24 h MP. RESULTS: (1) Reperfusion results were
      inferior in the UW group; (2) less damage and improved function were seen after
      wash-out using Polysol at 37 degrees C; (3) No effects were seen of the addition
      of heparin to Polysol; (4) MP after wash-out using HTK resulted in more liver
      damage and decreased liver function as compared with wash-out using Polysol.
      CONCLUSIONS: Polysol is applicable as a flush solution for the NHBD liver,
      resulting in equal to better wash-out as compared with UW and HTK. The best
      temperature for this NHBD wash-out is 37 degrees C.

PMID- 16911473
TI  - Increased angiogenesis and permeability in the mesenteric microvasculature of
      rats with cirrhosis and portal hypertension: an in vivo study.
AB  - BACKGROUND: In vivo evidence for angiogenesis in the splanchnic vasodilation in
      portal hypertension (PHT) and cirrhosis is lacking. Vascular endothelial growth
      factor (VEGF) and endothelial nitric oxide synthase (eNOS) are mediators of
      angiogenesis. The present study visualises in vivo structural changes
      (angiogenesis and vascular hyperpermeability) and examines the presence of VEGF
      and eNOS in the mesenteric microvasculature of animal models of PHT with and
      without cirrhosis. METHODS: Portal hypertension was induced by partial portal
      vein ligation (PPVL) and cirrhosis was induced by common bile duct ligation
      (CBDL) in rats. The mesenteric microcirculation was examined by intravital
      microscopy. Expression of VEGF, eNOS and CD31 in mesenteric tissue were studied
      by immunohistochemistry. RESULTS: An increased mesenteric angiogenesis was
      observed in PPVL and CBDL rats compared with Sham-operated and control rats, as
      shown by intravital microscopy and CD 31 staining. VEGF and eNOS expression was
      higher in CBDL and PPVL rats compared with control groups and correlated
      positively with vascular density. Macromolecular leakage was increased in
      cirrhotic rats compared with control and PPVL rats. CONCLUSION: Our study
      provides in vivo evidence of an increased angiogenesis in the mesenteric
      microvasculature of animal models of PHT and cirrhosis. Increased VEGF and eNOS
      expression in the mesentery of PPVL and CBDL rats may suggest their contribution.
      Microvascular permeability in the mesenteric vessels was only increased in
      cirrhotic rats.

PMID- 16911474
TI  - Unexplained CK elevations in patients with nonalcoholic steatohepatitis.

PMID- 16911476
TI  - Consequential apoptosis in the cerebellum following injury to the developing rat
      forebrain.
AB  - In focal brain lesions, alterations in blood flow and cerebral metabolism can be
      detected in brain areas remote from the primary injury. The cellular consequences
      of this phenomenon, originally termed diaschisis, are not fully understood. Here,
      we report that in two distinct models of forebrain injury, neuronal death in the
      cerebellum, a site distant to the primary injury, results as consequence of
      neuronal loss in the forebrain. Fourteen-day-old rats were subjected to
      unilateral forebrain injury, achieved by either hypoxia-ischemia (right carotid
      artery ligation and hypoxia) or direct needle injury to brain tissue. At defined
      times after injury, the presence of apoptosis was investigated by cell
      morphology, in situ end labeling, electron microscopy and poly-ADP-ribose
      polymerase (PARP) cleavage. Injury to the rat forebrain following hypoxia
      ischemia increased apoptosis in the internal granular and Purkinje cell layers of
      the cerebellum, a site distant to that of the primary injury. The number of
      apoptotic cells in the cerebellum was significantly related to cell death in the
      hippocampus. Similarly, direct needle injury to the forebrain resulted in
      extensive apoptotic cell death in the cerebellum. These results emphasize the
      intimate relationship between defined neuronal populations in relatively distant
      brain areas and suggest a cellular basis for diaschisis.

PMID- 16911477
TI  - Spinal cord gray matter demyelination in multiple sclerosis-a novel pattern of
      residual plaque morphology.
AB  - The extent and pattern of gray matter (GM) demyelination in the spinal cord in
      multiple sclerosis (MS) has not been examined in detail. Human autopsy material
      was obtained from 36 MS cases and 12 controls. Transverse sections were taken
      from five levels of the spinal cord (upper cervical, lower cervical, upper
      thoracic, lower thoracic and lumbar levels) and the extent of GM and white matter
      (WM) demyelination evaluated using proteolipid protein immunohistochemistry
      (IHC). The proportion of the GM that was demyelinated (33%) was significantly
      greater than the proportion of demyelinated WM (20%) (P < 0.0001). Similarly,
      demyelination was more extensive in the GM than in the WM at each of the five
      cord levels. The extent of GM demyelination was not significantly different
      between the five cord levels while WM demyelination was greatest at the upper
      cervical level. Morphologically, the borders of a proportion of the GM plaques
      show a strict respect for the GM/WM boundary. We demonstrate that extensive
      demyelination occurs in the GM of the spinal cord in MS. Myelin protein IHC
      reveals a novel pattern of residual plaque morphology challenging previous work
      suggesting that MS plaques display a total disregard for anatomical boundaries.

PMID- 16911478
TI  - Intrauterine exposure to dexamethasone impairs proliferation but not neuronal
      differentiation in the dentate gyrus of newborn common marmoset monkeys.
AB  - Glucocorticoids applied prenatally alter birth weight and the maturation of the
      lungs. Moreover, glucocorticoids impair neuronal proliferation and
      differentiation in the hippocampal dentate gyrus. In the present study
      proliferation and neuronal differentiation in the dentate gyrus were studied in
      newborn common marmoset monkeys which were intrauterinely exposed to the
      synthetic glucocorticoid dexamethasone (DEX). Pregnant marmoset monkeys received
      DEX (5 mg/kg body weight) daily either during early (days 42-48) or late (days 90
      96) pregnancy. In the hippocampi of newborn monkeys immunohistochemistry was
      performed with markers of proliferation (Ki-67), apoptosis (in situ tailing) as
      well as early and late neuronal differentiation (calretinin and calbindin). Both
      after early and late intrauterine exposure to DEX, proliferation of dentate gyrus
      cells was significantly decreased (P < 0.05). The density of apoptotic neurons
      was not altered by DEX treatment. Quantification of calretinin- and calbindin
      immunoreactive neurons showed no significant differences between DEX-exposed and
      control animals. In conclusion, the proliferation of putative precursor cells but
      not the differentiation into mature cells was impaired in the dentate gyrus of
      newborn marmosets exposed intrauterinely to DEX.

PMID- 16911479
TI  - Spinocerebellar ataxia type 3 (SCA3): thalamic neurodegeneration occurs
      independently from thalamic ataxin-3 immunopositive neuronal intranuclear
      inclusions.
AB  - In the last years progress has been made regarding the involvement of the
      thalamus during the course of the currently known polyglutamine diseases.
      Although recent studies have shown that the thalamus consistently undergoes
      neurodegeneration in Huntington's disease (HD) and spinocerebellar ataxia type 2
      (SCA2) it is still unclear whether it is also a consistent target of the
      pathological process of spinocerebellar ataxia type 3 (SCA3). Accordingly we
      studied the thalamic pathoanatomy and distribution pattern of ataxin-3
      immunopositive neuronal intranuclear inclusions (NI) in nine clinically diagnosed
      and genetically confirmed SCA3 patients and carried out a detailed statistical
      analysis of our findings. During our pathoanatomical study we disclosed (i) a
      consistent degeneration of the ventral anterior, ventral lateral and reticular
      thalamic nuclei; (ii) a degeneration of the ventral posterior lateral nucleus and
      inferior and lateral subnuclei of the pulvinar in the majority of these SCA3
      patients; and (iii) a degeneration of the ventral posterior medial and lateral
      posterior thalamic nuclei, the lateral geniculate body and some of the limbic
      thalamic nuclei in some of them. Upon immunocytochemical analysis we detected NI
      in all of the thalamic nuclei of all of our SCA3 patients. According to our
      statistical analysis (i) thalamic neurodegeneration and the occurrence of ataxin
      3 immunopositive thalamic NI was not associated with the individual length of the
      CAG-repeats in the mutated SCA3 allele, the patients age at disease onset and the
      duration of SCA3 and (ii) thalamic neurodegeneration was not correlated with the
      occurrence of ataxin-3 immunopositive thalamic NI. This lack of correlation may
      suggest that ataxin-3 immunopositive NI are not immediately decisive for the fate
      of affected nerve cells but rather represent unspecific and pathognomonic
      morphological markers of SCA3.

PMID- 16911480
TI  - Neurodegeneration with features of NIFID and ALS--extended clinical and
      neuropathological spectrum.
AB  - Heterogeneous clinical and neuropathological features have been observed in the
      recently described neuronal intermediate filament inclusion disease (NIFID). The
      immunohistological findings common to all cases are alpha-internexin and
      neurofilament-positive neuronal cytoplasmic inclusions, which have not been found
      in comparable density in other neurodegenerative disorders. Notwithstanding these
      common features, the cases reported so far have shown differences concerning age
      at onset, constellation and dominance of symptoms as well as type and
      distribution of additional neuropathological findings. Here we present the first
      NIFID case that exhibits severe involvement of lower motor neurons. Also, this
      patient may have had a clinical onset of disease in early childhood, as she was
      diagnosed as having dysarthria, which could not be attributed to any other cause
      at the age of 3 years. This case is a further contribution to the spectrum of
      this novel neurodegenerative disease.

PMID- 16911481
TI  - A 70-year-old man with extrapyramidal symptoms, dementia and hemosiderosis.

PMID- 16911482
TI  - A 49-year-old man with neuropsychiatric symptoms followed by progressive
      cognitive decline.

PMID- 16911483
TI  - 21-year-old woman with a cystic brain lesion.

PMID- 16911484
TI  - Food allergy after liver transplantation - is it the result of T-cell imbalance?

PMID- 16911485
TI  - Organ transplantation, organ donation and mental retardation.

PMID- 16911486
TI  - Renal transplantation in patients with Alport syndrome.
AB  - For pediatric kidney transplant physicians, two aspects of Alport syndrome set
      the disease apart from other causes of terminal renal failure. First, an
      understanding of the genetics of Alport syndrome is needed to make appropriate
      decisions regarding potential related kidney donors to Alport patients requiring
      renal transplantation. Second, renal transplantation for Alport syndrome may be
      complicated by post-transplant anti-GBM nephritis, a problem that is nearly
      unique to this disease. This review discusses these aspects of Alport syndrome
      and attempts to provide rational recommendations for clinicians.

PMID- 16911487
TI  - Organ transplantation, organ donation and mental retardation.
AB  - We reviewed the literature on accessibility and outcomes of organ transplantation
      in individuals with mental retardation (MR) and on the prevalence of organ
      donation in this population. Six centers have published outcome data on renal
      transplantation in 34 individuals with MR. The one- and three-yr patient survival
      rates were 100% and 90%, respectively. The studies reported good compliance with
      post-transplant medications due to consistent support from family members or
      caregivers. The outcome studies for liver and heart transplantation among these
      individuals are limited. The literature on organ donation in individuals with MR
      is mostly concerned with legal issues. The courts generally permit organ
      donations when such is in the best interests of the donor.

PMID- 16911488
TI  - Frequency of hyperuricemia and effect of calcineurin inhibitors on serum uric
      acid levels in liver transplanted children.
AB  - Hyperuricemia is common after renal and cardiac transplantations, but it is
      rarely reported after liver transplantations. The aim of this study is to
      determine the frequency of hyperuricemia in children following orthotopic liver
      transplantation and the effects of calcineurin inhibitors tacrolimus and
      cyclosporine) on blood uric acid levels. Between September 1997 to January 2004,
      76 liver transplantations were performed in 70 children (male/female; 39/31) at
      Ege University, Organ Transplantation Center (37 deceased donation and 39 live
      donors). Patients who had been transplanted within the last three months and
      patients who died within six months after liver transplantation were excluded
      from the study. Finally 59 patients were included in this study. Uric acid levels
      were measured before transplantation and after transplantation within six months
      intervals for two yr. In these series 17 cases had increased uric acid levels
      after liver transplantation (28.8%). Serum uric acid levels in both groups
      (tacrolimus or cyclosporine) were detected to be significantly higher than
      initial values at 12th months (p < 0.05). Hyperuricemia developed in eight
      patients receiving cyclosporine (eight of 11; 72%) whereas nine patients
      receiving tacrolimus developed hyperuricemia (nine of 48; 18%). However, the rate
      of having high uric acid levels was significantly higher in cyclosporine group
      compared tacrolimus group (p = 0.001, OR: 11.5, CI 95% 2.5-52.4). Uric acid
      levels were also significantly higher in cyclosporine group in 12th and 18th
      months (respectively, p = 0.003 and p = 0.003). Serum creatinine levels at 12th,
      18th and 24th months were significantly higher in cyclosporine group than
      tacrolimus group (respectively, p = 0.009, p = 0.04 and p = 0.02). Hyperuricemia
      is a common complication after liver transplantation in children. Cyclosporine
      may cause hyperuricemia more often in respect to tacrolimus and this may be
      related to the impairment of renal functions. Complications developing because of
      hyperuricemia such as gout disease or renal calculi are quite rare in children.

PMID- 16911489
TI  - A novel pattern of transaminase elevation associated with autologous transplant
      for neuroblastoma.
AB  - To determine the pattern and degree of hepatic transaminitis experienced by
      children undergoing autologous transplantation for neuroblastoma. Sixty-four
      children with high-risk neuroblastoma received an autologous transplant with
      cyclophosphamide, etoposide, and carboplatin conditioning. Forty-eight went on to
      receive a second transplant with M and TBI conditioning. Charts were reviewed for
      evidence of hepatic regimen-related toxicity. A high rate of transaminitis was
      observed after both regimens. In each transplant, there was an early period of
      transaminitis during conditioning, from which patients recovered, followed by a
      second period of transaminase elevation. The degree of elevation was not
      associated with age, whether the administered dose was calculated based on a per
      kg or per M(2) basis or the presence of regimen-related severe mucositis.
      Elevated transaminases at admission were not associated with maximal
      hepatotoxicity during the first transplant although there was an association in
      the second transplant. However, the magnitude of transaminase elevation was less
      in the second transplant. VOD occurred in one and three patients in transplants 1
      and 2, respectively. Both conditioning regimens were associated with an early and
      late elevation of transaminases without significant cholestasis. This biphasic
      pattern of transaminitis has not been reported previously. The high prevalence of
      transaminase elevation at time of both transplants was not associated with an
      increased incidence of VOD. We conclude that elevated transaminases should not
      preclude proceeding to a first or second autologous transplant with these
      regimens.

PMID- 16911490
TI  - Immunosuppression in infants with short bowel syndrome undergoing isolated liver
      transplantation.
AB  - BACKGROUND: Little data exist on immunosuppressive drug absorption in children
      with short bowel syndrome and intestinal failure associated liver disease (SBS
      IFALD). AIM: To evaluate the absorption of immunosuppressive medications in
      children with SBS-IFALD undergoing isolated liver transplantation (iLTx).
      METHODS: A retrospective review was performed in children with SBS-IFALD
      undergoing LTx and comparison made with weight, age-matched children undergoing
      iLTX (extra-hepatic biliary atresia (EHBA) and normal intestinal length and
      function). RESULTS: Seven children with SBS-IFALD undergoing iLTx (median
      residual bowel length, 60 cm, range 40-80) were compared with 15 children
      undergoing LTx for EHBA. SBS-IFALD children had significantly lower trough
      tacrolimus levels at three months (5.8 vs. 7.9 ng/mL, p<0.05) and six months (5.0
      vs. 8.0 ng/mL, p<0.05), but equivalent levels at 12 months after iLTx. The median
      calculated dose-normalized concentrations indicated that systemic availability of
      tacrolimus was comparable in two groups at 3, 6, 12 months (33.1 vs. 23.3; 42.4
      vs. 36; 51 vs. 52.9) despite the differences in enteral function. The incidence
      of acute rejection was 1/7 (SBS-IFALD) and 10/15 (EHBA) group (p = 0.06).
      CONCLUSION: Children with SBS-IFALD demonstrated adequate absorption of oral
      tacrolimus without significant acute rejection rate after iLTx suggesting that
      modification of immunosuppression is not necessary.

PMID- 16911491
TI  - Incidence, etiology, and risk factors for liver dysfunction in children following
      hematopoietic stem cell transplantation.
AB  - AIMS: To identify risk factors which predispose children to develop liver
      dysfunction (LD) during the initial 100 days following hematopoietic stem cell
      transplantation (HSCT). METHODS: Retrospective analysis of all patients (<21 yr)
      who had undergone HSCT from July 1998 to June 2003. LD was defined by the
      presence of clinical jaundice and/or elevated alanine aminotransferase (ALT) or
      gamma-glutamyl transferase (GGT) (1.5 times normal). RESULTS: One hundred and six
      patients underwent HSCT during the study period. LD was seen in 91 (85.5%)
      patients and the majority (58.2%) had moderate to severe LD. The primary cause of
      LD could be ascertained in 2/3 of patients and was multifactorial in the rest.
      The odds ratio and 95% CI for risk factors associated with LD following HSCT on
      univariate analysis were as follows: allogeneic source of stem cells 4.2 (1.2
      14.2), engraftment >12 days 4.3 (1.3-14.2), total parenteral nutrition >35 days
      8.2 (1.1-66.2), pretransplant ALT >40 U/L 7.4 (0.9-58.6), use of cyclosporine and
      methotrexate 9.5 (1.2-77.9), and use of amphotericin-B 3.1 (0.9-10.6). On
      multivariate analysis only elevated pre transplantation ALT and delayed
      engraftment were associated with post-HSCT LD. LD was seen in all 13 patients who
      died within 100 days following HSCT, and it was felt to be the primary cause of
      death in six (46%) patients. The factors associated with increased risk of
      mortality were: allogeneic source of stem cells, delayed engraftment (>18 days),
      higher mean peak GGT (>250 U/L), and total bilirubin (>6 mg/dL). CONCLUSION: LD
      was common and severe in the majority of children following HSCT. Risk of LD was
      higher in children who had elevated pretransplantation ALT or had delayed
      engraftment. LD contributes significantly to morbidity and mortality following
      HSCT.

PMID- 16911492
TI  - Tacrolimus immunosuppression - an association with asymptomatic eosinophilia and
      elevated total and specific IgE levels.
AB  - De novo development of food allergy is an infrequent but potentially serious
      complication of transplantation. An increased prevalence of food allergy noted
      specifically in children receiving tacrolimus immunosuppression supports the
      hypothesis that selective suppression of Th1 lymphocytes by the IL-2 inhibitor
      immunosuppressants CsA, and the more potent drug, tacrolimus , promotes Th2
      lymphocytes and an allergic immune response. This study was undertaken to
      characterize the IgE-mediated immune response, in CsA and tacrolimus-treated,
      post-OLT children. Thirty children and adolescents aged 1.9-21 yr, mean: 10.6 yr,
      (6.4 yr post-tx.) were studied. Immunosuppression-CsA: 10 patients, tacrolimus;
      20 patients. Blood eosinophils, total IgE levels and specific IgE antibodies
      (Immulite 2000 Allergy; Diagnostic Products Corp., Los Angeles, CA, USA) to a
      panel of food and inhaled allergens were measured and correlated with clinical
      symptoms of allergy. Eosinophilia (>500/mm(3)) range: 599-3125, mean: 1294, was
      present in 10/20 of patients treated with tacrolimus and 1/10 treated with CsA.
      IgE levels were elevated in eight of these 10 tacrolimus-treated patients and in
      two CsA patients ; five were <3 yr of age and IgE levels ranged from 54 to 111
      IU/mL (mean: 83), normal for age <45 IU/mL and five were > or =9 yr and IgE
      levels ranged from 134 to 1606 IU/mL (mean: 557), normal for age <87 IU/mL.
      Specific IgE levels to a wide panel of food allergens were positive in five
      tacrolimus-treated patients and to both food and inhaled allergens in three
      patients (two tacrolimus-treated, one CsA). Four children (tacrolimus-treated)
      had symptoms of food allergy . None had a family history of allergy. Eosinophilia
      is present in up to 50% of children and adolescents receiving tacrolimus
      immunosuppression. The majority of these patients also have elevated levels of
      total and specific (mainly to food allergens) IgE antibodies. Most patients are
      asymptomatic and do not manifest food allergy or asthma.

PMID- 16911493
TI  - Adherence in adolescents and young adults following heart or heart-lung
      transplantation.
AB  - To assess the prevalence and some potential correlates of non-adherence to
      medications in adolescent and young adult transplant patients. Fifty patients who
      had undergone heart or heart-lung transplantation 1.4-14.9 yr (mean 8.8 yr)
      previously completed the Beliefs about Medication Questionnaire (BMQ), Perceived
      Illness Experience (PIE) scale and a demographics questionnaire. Medical notes
      were reviewed for information regarding previous psychiatric referral, rejection
      episodes and complications and noted concerns about adherence. Forty (80%)
      completed questionnaires were received. Non-adherence determined from the
      questionnaires was associated with forgetting to take medication and was
      classified as unintentional non-adherence. Such non-adherence was reported by 11
      (28%) patients. Seven patients (18%) showed evidence from their records of
      deliberate non-adherence, which was classified as intentional. Whilst intentional
      non-adherence was associated with depression and transplant-related lymphoma,
      unintentional non-adherence and perceived difficulties with medications were
      associated with high scores on the PIE preoccupation with illness and BMQ
      concerns subscale and with drinking alcohol. Future research is required to
      determine whether unintentional non-adherence results in significant medical
      complications in the longer term and how a reduction in the prevalence of non
      adherence can be facilitated.

PMID- 16911494
TI  - Pattern of growth after pediatric living-donor small bowel transplantation.
AB  - The aim of our study was to analyze growth in children who underwent LDSB. The
      question was whether these children obtain linear growth and improvement of the Z
      score for height and weight after the transplant. Three children with a mean age
      of 24 months underwent living-donor intestinal transplantation with 150 cm of
      terminal ileum. At a mean follow-up of 27 months height increased from 82.5 to
      97.5 cm although Z-score for height did not improve, -2.679 to -2.675. Mean
      weight increased from 11.4 to 14.2 kg while Z-score for weight went from -1.916
      to -2.409. Although these data are pertinent to only three children and the
      follow-up is slightly longer than two yr, it appears that while long-term
      survival and independency from TPN is achieved, only linear growth might be
      expected and catch-up growth does not occur.

PMID- 16911495
TI  - Value of therapeutic drug monitoring of MMF therapy in pediatric transplantation.
AB  - Therapeutic drug monitoring (TDM) is desirable whenever the desired drug effect
      cannot be predicted from a given dose, or when it is necessary to find a balance
      between the efficacy and toxicity of the drug. Children and adolescents
      particularly benefit from TDM, because dosing requirements are often not studied
      in the same detail as in adults. Also, drug-drug interactions are frequent. The
      gold standard for assessment of drug exposure is the area-under-the-curve (AUC)
      for a full pharmacokinetic profile. TDM for mycophenolic acid (MPA) is less well
      established. Monitoring of trough levels does not suffice because of
      enterohepatic recirculation of MPA after formation of its main metabolite, a
      glucoronide termed MPA-G. However, abbreviated sampling schemes specific to
      mycophenolate mofetil (MMF) correlate well with the AUC for MPA. Cyclosporine
      interacts with MPA by inhibiting the multidrug resistance-associated protein 2
      (MRP2). Higher MPA concentrations result in a decreased two h concentration of
      cyclosporine, while higher cyclosporine exposure results in a lower MPA exposure.
      There are no drug interactions between tacrolimus and MPA, and lower doses of MMF
      are required in combination with tacrolimus. Steroids may induce the clearance of
      MPA, which could account in part for the increasing MPA exposure following
      transplantation. TDM has allowed for dosing recommendations of MMF in children,
      which could lead to improved efficacy and minimization of toxicities. It is
      important that these provisional target levels are validated in prospective
      studies. The above points clearly indicate that there is a role for TDM of MPA in
      pediatric transplant recipients.

PMID- 16911496
TI  - Current issues in pediatric transplantation.
AB  - Pediatric solid organ transplantation is so successful that >80% of children will
      survive to become teenagers and adults. Therefore, it is essential that these
      children maintain a good quality life, free of significant long-term side
      effects. While intensive immunosuppressive regimens (containing CsA, tacrolimus,
      MMF, and steroids) effectively reduce acute or chronic rejection, they can
      produce long-term side effects including viral infection, renal dysfunction,
      hypertension, and stunting. The development of effective methods of diagnosis,
      prevention, and treatment of CMV means that this is no longer a significant cause
      of mortality, but morbidity remains high. In contrast, infection rates of EBV
      remain high in EBV-negative pre-transplant patients. However, pre-emptive
      reduction of immunosuppression or treatment with rituximab or adoptive T-cell
      therapy is effective in preventing/treating post-transplant lymphoproliferative
      disease. Recent protocols have concentrated on reducing CsA immunosuppression, to
      prevent unacceptable cosmetic effects, and to reduce the hypertension,
      hyperlipidemia, and nephrotoxicity. Both CsA and tacrolimus cause a 30% reduction
      in renal function, with 4-5% of patients developing severe chronic renal failure.
      The use of IL-2 inhibitors for induction therapy with low-dose calcineurin
      inhibitors, in combination with renal-sparing drugs such as MMF or sirolimus for
      maintenance immunosuppression, should prevent significant renal dysfunction in
      the future. The concept of steroid-free immunosuppression with IL-2 inhibitors,
      tacrolimus, and MMF is an attractive option, which may reduce stunting and renal
      dysfunction. However, these regimens may be associated with the increased
      development of de-novo autoimmune hepatitis in 2-3% of children. The most
      important challenge to long-term survival in transplanted children is the
      management of non-adherence and other adolescent issues, particularly when
      transferring to adult units, as this is the time when many successful transplant
      survivors lose their grafts.

PMID- 16911497
TI  - Treatment strategies in pediatric solid organ transplant recipients with
      calcineurin inhibitor-induced nephrotoxicity.
AB  - Although short-term kidney allograft survival has improved significantly since
      the introduction of the calcineurin inhibitors (CNI) cyclosporine A (CsA) and
      tacrolimus, long-term transplant survival remains a major concern, chronic
      allograft nephropathy (CAN) being the principal reason for graft loss after the
      first post-transplant year. This is particularly major for pediatric renal
      transplant recipients because of their higher life expectancy compared with
      adults. The mechanisms leading to CAN are multiple, including acute and chronic
      alloimmune responses and nephrotoxicity of CNIs. CNI-induced nephrotoxicity is
      also a long-term concern in other pediatric solid organ transplant recipients,
      such as liver and heart. Prevention of allograft nephropathy requires a balance
      of maintaining adequate immunosuppression, while avoiding the toxic effects of
      CNIs. Regimens that are based on mycophenolate mofetil (MMF) alone or in
      combination with newer agents may allow for reduced reliance on CNIs and thus may
      represent an effective treatment paradigm for long-term maintenance of a renal
      allograft. From the available data it appears that the currently safest treatment
      strategy in pediatric renal and heart transplant recipients with CNI toxicity is
      an MMF-based therapy with low-dose CNIs +/- low-dose steroids, while in pediatric
      liver transplant recipients, CNI-free MMF-based immunosuppressive therapy with or
      without steroids appears feasible in a significant subset of patients. In renal
      transplant recipients, the benefit of a CNI-free MMF/steroid therapy on renal
      function is gained at the cost of increased rejection in a subset of patients,
      although the relative importance of rejection vs. overall renal function requires
      further clinical investigation. The introduction of mammalian target of rapamycin
      (mTOR) inhibitors provides an opportunity for unique CNI-sparing regimens that
      combine two antiproliferative agents (MMF and TOR inhibitors). It is possible
      that a sirolimus-based CNI-free immunosuppressive regimen in terms of renal
      transplant survival is superior to CNI minimization, where the detrimental
      effects of CNIs on allograft function and structure are still operative, albeit
      to a lesser degree. Substitution of CNIs by mTOR inhibitors is therefore
      promising, but requires validation in long-term studies in large cohorts.

PMID- 16911498
TI  - Tacrolimus-associated eosinophilic gastroenterocolitis in pediatric liver
      transplant recipients: role of potential food allergies in pathogenesis.
AB  - Tacrolimus is a macrolide agent that is now the primary immunosuppressant used in
      prevention of graft rejection in transplant recipients. It has been found to be
      superior to cyclosporine (CSA) for rescue therapy as well as for earlier weaning
      of steroids. Both tacrolimus and CSA share similar toxicity profiles; however,
      their gastrointestinal side effects have received little attention. We report
      three cases of eosinophilic colitis in liver transplant recipients, maintained on
      tacrolimus as immunosuppressive medication post-liver transplantation. These
      patients also had high serum immunoglobulin (Ig)E levels, eosinophilia and IgE
      positive radioallergosorbent test for milk proteins. The colitis appeared to be
      mediated by food allergies. Each patient had symptomatic improvement following
      reduced immunosuppression and an appropriately restricted diet. We conclude that
      tacrolimus may play a role in the initiation of food allergies, leading to
      eosinophilic colitis. More studies are needed in a controlled setting to identify
      the prevalence of similar findings among other pediatric liver transplant
      recipients.

PMID- 16911499
TI  - Amiodarone-sirolimus/tacrolimus interaction in a pediatric heart transplant
      patient.
AB  - A two year-old female who had underwent ABO-incompatible heart transplantation at
      four months of age was admitted with unexplained anemia and renal dysfunction.
      The patient also had evidence of moderate liver dysfunction. Maintenance
      immunosuppression consisted of tacrolimus, mycophenolate mofetil and
      prednisolone. Tacrolimus was held on day 2 for five days because of an elevated
      trough blood concentration. The patient required one fourth of her maintenance
      dose to keep trough concentrations within the target range. Nadolol and
      amiodarone were prescribed on day 7 to control ventricular arrhythmias. Sirolimus
      was prescribed on day 11. A precautionary (non-steady-state) sirolimus trough
      concentration was grossly elevated. Sirolimus was held and tacrolimus was
      discontinued. Sirolimus blood concentrations remained above the target range for
      fourteen days despite successive dose manipulations. The patient succumbed from
      complications of ECMO on day 42. Amiodarone and cyclosporine interactions in the
      solid organ transplant population have been previously described. To our
      knowledge, there are no cases of amiodarone and sirolimus or tacrolimus
      interactions reported in English literature. Both tacrolimus and sirolimus are
      metabolized through the same enzyme system as cyclosporine, and the chance of a
      similar interaction occurring is high. Sirolimus is also a substrate of p
      glycoprotein and thus may be significantly affected by amiodarone. We have
      described a potential interaction with sirolimus, tacrolimus and amiodarone. If
      amiodarone is deemed the most appropriate choice for the patient, clinicians
      should consider prospectively decreasing sirolimus and tacrolimus doses. Blood
      concentrations should also be monitored more frequently in order to minimize
      prolonged periods of supratherapeutic concentrations and related toxicities.

PMID- 16911500
TI  - Immune-mediated hemolytic anemia in pediatric renal transplantation.
AB  - The aim of the study was to demonstrate clinical course of the first reported
      cases of PLS in pediatric kidney transplantation and therapeutic outcome for such
      condition using a combination of high-dose corticosteroid and tacrolimus. We
      report a single case (a nine-year-old Thai boy) with end-stage kidney disease
      secondary to obstructive uropathy developed immune-mediated hemolytic anemia from
      the PLS at second week after a pre-emptive living-related kidney transplantation.
      The alloimmune hemolysis was a result of anti-B antibodies, derived from blood
      group O-donor lymphocytes. Using a combination of high-dose corticosteroid and a
      substitution of cyclosporin with tacrolimus, there was no further hemolysis
      although the anti-B antibodies remained detectable until the eighth week post
      transplantation. An impairment of the graft function because of hemoglobinuria
      was resolved after the hemolysis was stopped. The alloimmune hemolysis caused by
      PLS in pediatric kidney transplantation could be controlled with a combination of
      high-dose corticosteroid and tacrolimus.

PMID- 16911501
TI  - Chimerism in a child with severe combined immunodeficiency: a case report.
AB  - Severe combined immunodeficiency (SCID) represents a group of rare, sometimes
      fatal, congenital disorders in which there is a combined absence of T-lymphocyte
      and B-lymphocyte function. Children with SCID die within two years of age, if
      untreated. The effective treatment for SCID is a hematopoietic stem cell
      transplantation (HSCT). It has been repeatedly described that in peripheral blood
      of infants with SCID maternal T cells can be found. Here we report a case of
      blood chimerism in a one-year-old boy with SCID.

PMID- 16911502
TI  - Compliance following living kidney transplantation - is there a need for long
      term psychological counselling in adolescents at risk?

PMID- 16911503
TI  - Comments on 'Skin transplantation to monitor clinical donor-related tolerance in
      mixed hematopoietic chimerism' by Mache et al. (Pediatr Transplant 2006;10:128
      131).

PMID- 16911505
TI  - Tissue typing for hematopoietic cell transplantation: HLA-DQB1 typing should be
      included.

PMID- 16911506
TI  - Should skin grafts be used to test for tolerance?

PMID- 16911507
TI  - Mitochondrial preprotein translocases as dynamic molecular machines.
AB  - Proteomic studies have demonstrated that yeast mitochondria contain roughly 1000
      different proteins. Only eight of these proteins are encoded by the mitochondrial
      genome and are synthesized on mitochondrial ribosomes. The remaining 99% of
      mitochondrial precursors are encoded within the nuclear genome and after their
      synthesis on cytosolic ribosomes must be imported into the organelle. Targeting
      of these proteins to mitochondria and their import into one of the four
      mitochondrial subcompartments--outer membrane, intermembrane space (IMS), inner
      membrane and matrix--requires various membrane-embedded protein translocases, as
      well as numerous chaperones and cochaperones in the aqueous compartments. During
      the last years, several novel protein components involved in the import and
      assembly of mitochondrial proteins have been identified. The picture that emerges
      from these exciting new findings is that of highly dynamic import machineries,
      rather than of regulated, but static protein complexes. In this review, we will
      give an overview on the recent progress in our understanding of mitochondrial
      protein import. We will focus on the presequence translocase of the inner
      mitochondrial membrane, the TIM23 complex and the presequence translocase
      associated motor, the PAM complex. These two molecular machineries mediate the
      multistep import of preproteins with cleavable N-terminal signal sequences into
      the matrix or inner membrane of mitochondria.

PMID- 16911508
TI  - Use of population genetics to derive nonrecombinant Saccharomyces cerevisiae
      strains that grow using xylose as a sole carbon source.
AB  - According to scientific dogma, Saccharomyces cerevisiae cannot grow utilizing
      xylose as a sole carbon source. Although recombinant DNA technology has overcome
      this deficiency to some degree, efficient utilization of xylose appears to
      require complex global changes in gene expression. This complexity provides a
      significant challenge to the development of yeasts suitable for the utilization
      of xylose-rich lignocellulosic substrates. In contrast to the dogma, we have
      found that native strains of S. cerevisiae can grow on xylose as a sole carbon
      source, albeit very slowly. This observation provided the basis for a new
      approach using natural selection to develop strains of S. cerevisiae with
      improved ability to utilize xylose. By applying natural selection and breeding
      over an extended period, we have developed S. cerevisiae strains that can double
      in less than 6 h using xylose as a sole carbon source. Strains with improved
      growth rate possessed increased xylose reductase and xylitol dehydrogenase
      activities, with the latter showing the greater improvement. This unique,
      completely nonrecombinant approach to developing xylose-utilizing strains of S.
      cerevisiae opens an alternative route to the development of yeast that can fully
      utilize lignocellulosic substrates.

PMID- 16911509
TI  - The COX18 gene, involved in mitochondrial biogenesis, is functionally conserved
      and tightly regulated in humans and fission yeast.
AB  - The biogenesis of cytochrome c oxidase requires coordination between the nucleus
      and mitochondria because both these compartments provide the structural subunits
      of this enzyme. In addition, synthesis, membrane insertion and assembly of the
      mitochondrially encoded subunits are controlled in a concerted way by numerous
      nuclear-encoded factors, including Oxa1 and Cox18, which play successive roles in
      Cox2 assembly in Saccharomyces cerevisiae. These two factors share a weak
      structural similarity and define two sub-branches of the Oxa1/YidC/Alb3 gene
      family, whose members facilitate the membrane insertion of various hydrophobic
      proteins into diverse biological membranes. In this study, we have analyzed a
      second human and a third fission yeast member of the family. We show, by deletion
      in the fission yeast genome, as well as expression and functional complementation
      experiments in both yeasts, that these new genes belong to the COX18 rather than
      to the OXA1 sub-branch. So far, the fission yeast gene cox18Sp+ is the smallest
      functional member of this gene family. COX18Hs gives rise to various mRNAs with
      different coding capacities, and we show that cox18Sp+ and COX18Hs are expressed
      at a low level and appear to be stringently regulated. This transcriptional
      control contrasts with the constitutive abundance of the OXA1 mRNAs and might
      reflect major functional differences between these nevertheless structurally
      related genes.

PMID- 16911510
TI  - Heat shock-inducible expression vectors for use in Schizosaccharomyces pombe.
AB  - A new, heat shock-inducible expression system based on an endogenous hsp16+
      promoter was developed for use in the fission yeast Schizosaccharomyces pombe.
      Analysis of GFP expression profiles indicated that a 1.2-kb segment of the hsp16+
      promoter region was sufficient to drive expression of heterologous protein. The
      hsp16+ promoter was found to be activated not only by heat shock but also by
      other stresses including cadmium, ethanol, and oxidative stress. Two expression
      vectors, pHIL and pHIU, were constructed using the 1.2-kb hsp16+ promoter for
      inducible gene expression in Sch. pombe. This new expression system utilizes a
      simple induction protocol and promises to be a useful tool for analyzing gene
      expression in Sch. pombe.

PMID- 16911511
TI  - Physiological characterization and fed-batch production of an extracellular
      maltase of Schizosaccharomyces pombe CBS 356.
AB  - The fission yeast Schizosaccharomyces pombe CBS 356 exhibits extracellular
      maltase activity. This activity may be of commercial interest as it exhibited a
      low pH optimum (3.5) and a high affinity for maltose (Km of 7.0+/-1.8 mM). N
      terminal sequencing of the protein indicates that it is the product of the AGL1
      gene. Regulation of this gene occurs via a derepression/repression mechanism. In
      sugar- or nitrogen-limited chemostat cultures, the specific rate of enzyme
      production (q(p)) was independent of the nature of the carbon source (i.e.
      glucose or maltose), but synthesis was partially repressed by high sugar
      concentrations. Furthermore, q(p) increased linearly with specific growth rate
      (mu) between 0.04 and 0.10 h(-1). The enzyme is easily mass-produced in aerobic
      glucose-limited fed-batch cultures, in which the specific growth rate is
      controlled to prevent alcoholic fermentation. In fed-batch cultures in which
      biomass concentrations of 83 g L(-1) were attained, the enzyme concentration
      reached 58,000 Units per liter culture supernatant. Extracellular maltase may be
      used as a dough additive in order to prevent mechanisms such as maltose-induced
      glucose efflux and maltose-hypersensitivity that occur in maltose-consuming
      Saccharomyces cerevisiae.

PMID- 16911512
TI  - Intracellular trehalose is neither necessary nor sufficient for desiccation
      tolerance in yeast.
AB  - Trehalose is thought to be important for desiccation tolerance in a number of
      organisms, including Saccharomyces cerevisiae, but there is limited in vivo
      evidence to support this hypothesis. In wild-type yeast, the degree of
      desiccation tolerance has been shown previously to increase in cultures after
      diauxic shift and also in exponential-phase cultures after exposure to heat
      stress. Under both these conditions, increased survival of desiccation correlates
      with elevated intracellular trehalose concentrations. Our data confirm these
      findings, but we have tested the apparent importance of trehalose using mutant
      strains with a deleted trehalose-6-phosphate synthase gene (tps1Delta). Although
      tps1Delta strains do not produce trehalose, they are nevertheless capable of
      desiccation tolerance, and the degree of tolerance also increases after diauxic
      shift or heat stress, albeit slightly less than in the wild type. Conversely,
      when wild-type yeast is subjected to osmotic stress, mid-exponential-phase
      cultures produce high concentrations of intracellular trehalose but show little
      improvement in desiccation tolerance. These results show that there is no
      consistent relationship between intracellular trehalose levels and desiccation
      tolerance in S. cerevisiae. Trehalose seems to be neither necessary nor
      sufficient for, although in some strains might quantitatively improve, survival
      of desiccation, suggesting that other adaptations are more important.

PMID- 16911513
TI  - The mechanism by which overexpression of Gts1p induces flocculation in a FLO8
      inactive strain of the yeast Saccharomyces cerevisiae.
AB  - GTS1 induces flocculation when overexpressed in the Saccharomyces cerevisiae
      strain W303-1A, which carries a mutant FLO8, the activator of flocculin genes.
      Herein, we report that the GTS1-induced flocculation was flocculin-dependent in
      nature and was caused by expression of the major flocculin Flo1p. Gts1p bound to
      the repressor Sfl1p, and their interaction at the transcriptional level was shown
      by reporter gene assays using the FLO1 promoter, suggesting that Gts1p induces
      the expression of FLO1 by inhibiting Sfl1p. Furthermore, the Q-rich domain with
      the preceding 18 amino acids of Gts1p bound mediators for RNA polymerase II.

PMID- 16911514
TI  - Yeast genes involved in response to lactic acid and acetic acid: acidic
      conditions caused by the organic acids in Saccharomyces cerevisiae cultures
      induce expression of intracellular metal metabolism genes regulated by Aft1p.
AB  - Using two types of genome-wide analysis to investigate yeast genes involved in
      response to lactic acid and acetic acid, we found that the acidic condition
      affects metal metabolism. The first type is an expression analysis using DNA
      microarrays to investigate 'acid shock response' as the first step to adapt to an
      acidic condition, and 'acid adaptation' by maintaining integrity in the acidic
      condition. The other is a functional screening using the nonessential genes
      deletion collection of Saccharomyces cerevisiae. The expression analysis showed
      that genes involved in stress response, such as YGP1, TPS1 and HSP150, were
      induced under the acid shock response. Genes such as FIT2, ARN1 and ARN2,
      involved in metal metabolism regulated by Aft1p, were induced under the acid
      adaptation. AFT1 was induced under acid shock response and under acid adaptation
      with lactic acid. Moreover, green fluorescent protein-fused Aft1p was localized
      to the nucleus in cells grown in media containing lactic acid, acetic acid, or
      hydrochloric acid. Both analyses suggested that the acidic condition affects cell
      wall architecture. The depletion of cell-wall components encoded by SED1, DSE2,
      CTS1, EGT2, SCW11, SUN4 and YNL300W and histone acetyltransferase complex
      proteins encoded by YID21, EAF3, EAF5, EAF6 and YAF9 increased resistance to
      lactic acid. Depletion of the cell-wall mannoprotein Sed1p provided resistance to
      lactic acid, although the expression of SED1 was induced by exposure to lactic
      acid. Depletion of vacuolar membrane H+-ATPase and high-osmolarity glycerol
      mitogen-activated protein kinase proteins caused acid sensitivity. Moreover, our
      quantitative PCR showed that expression of PDR12 increased under acid shock
      response with lactic acid and decreased under acid adaptation with hydrochloric
      acid.

PMID- 16911515
TI  - A new physiological role for Pdr12p in Saccharomyces cerevisiae: export of
      aromatic and branched-chain organic acids produced in amino acid catabolism.
AB  - Saccharomyces cerevisiae can use a broad range of compounds as sole nitrogen
      source. Many amino acids, such as leucine, tyrosine, phenylalanine and
      methionine, are utilized through the Ehrlich pathway. The fusel acids and
      alcohols produced from this pathway, along with their derived esters, are
      important contributors to beer and wine flavor. It is unknown how these compounds
      are exported from the cell. Analysis of nitrogen-source-dependent transcript
      profiles via microarray analysis of glucose-limited, aerobic chemostat cultures
      revealed a common upregulation of PDR12 in cultures grown with leucine,
      methionine or phenylalanine as sole nitrogen source. PDR12 encodes an ABC
      transporter involved in weak-organic-acid resistance, which has hitherto been
      studied in the context of resistance to exogenous organic acids. The hypothesis
      that PDR12 is involved in export of natural products of amino acid catabolism was
      evaluated by analyzing the phenotype of null mutants in PDR12 or in WAR1, its
      positive transcriptional regulator. The hypersensitivity of the pdr12Delta and
      war1Delta strains for some of these compounds indicates that Pdr12p is involved
      in export of the fusel acids, but not the fusel alcohols derived from leucine,
      isoleucine, valine, phenylalanine and tryptophan.

PMID- 16911516
TI  - The active essential CFNS3d protein complex.
AB  - The NS2B-NS3 protease complex is essential for the replication of dengue virus,
      which is the etiologic agent of dengue and hemorrhagic fevers, diseases that are
      a burden for the tropical and subtropical areas of the world. The active form of
      the NS3 protease linked to the 40 residues of the NS2B cofactor shows highly
      flexible and disordered region(s) that are responsible for its high propensity to
      aggregate at the concentrations necessary for NMR spectroscopy studies or for
      crystallization. Limited proteolysis of this active form of the protease enabled
      us to obtain a folded and new essential form of the NS2B-NS3 protease complex. We
      found that the region from residues D50 to E80 of NS2B interacts directly and
      strongly with the NS3 protease domain. The proteolytic activity of the
      noncovalently binding complex was determined by a rapid and continuous
      fluorescence resonance energy transfer activity assay using a depsipeptide
      substrate. The new protein-cofactor complex obtained, encompassing the NS2B
      fragment (D50-E80) and the NS3 protease, shows proteolytic activity. The (1)H
      (15)N-heteronuclear single quantum coherence spectrum of the isotopically
      enriched protein complex shows good cross-peak dispersion; this is indicative of
      a stable folded state. Our results significantly complement the X-ray structure
      of the NS2B-NS3pro complex published recently. Moreover, these results open the
      way to performing direct structural and interaction studies in solution on a new
      active NS2B-NS3pro complex with libraries of substrates and inhibitors in order
      to identify new drugs that prevent viral polyprotein processing.

PMID- 16911517
TI  - Expression and function of Noxo1gamma, an alternative splicing form of the NADPH
      oxidase organizer 1.
AB  - Activation of the superoxide-producing NADPH oxidase Nox1 requires both the
      organizer protein Noxo1 and the activator protein Noxa1. Here we describe an
      alternative splicing form of Noxo1, Noxo1gamma, which is expressed in the testis
      and fetal brain. The Noxo1gamma protein contains an additional five amino acids
      in the N-terminal PX domain, a phosphoinositide-binding module; the domain plays
      an essential role in supporting superoxide production by NADPH oxidase (Nox)
      family oxidases including Nox1, gp91(phox)/Nox2, and Nox3, as shown in this
      study. The PX domain isolated from Noxo1gamma shows a lower affinity for
      phosphoinositides than that from the classical splicing form Noxo1beta.
      Consistent with this, in resting cells, Noxo1gamma is poorly localized to the
      membrane, and thus less effective in activating Nox1 than Noxo1beta, which is
      constitutively present at the membrane. On the other hand, cell stimulation with
      phorbol 12-myristate 13-acetate (PMA), an activator of Nox1-3, facilitates
      membrane translocation of Noxo1gamma; as a result, Noxo1gamma is equivalent to
      Noxo1beta in Nox1 activation in PMA-stimulated cells. The effect of the five
      amino-acid insertion in the Noxo1 PX domain appears to depend on the type of Nox;
      in activation of gp91(phox)/Nox2, Noxo1gamma is less active than Noxo1beta even
      in the presence of PMA, whereas Noxo1gamma and Noxo1beta support the superoxide
      producing activity of Nox3 to the same extent in a manner independent of cell
      stimulation.

PMID- 16911518
TI  - Multiple promoters regulate tissue-specific alternative splicing of the human
      kallikrein gene, KLK11/hippostasin.
AB  - The human kallikrein (KLK) family consists of 15 genes located on human
      chromosome 19q13.4. KLK11/hippostasinis a member of the kallikrein family and is
      expressed in various tissues. Two types of KLK11 isoforms, isoform 1 and isoform
      2, have been predicted from cDNA sequences. Isoform 1 has been isolated from
      human hippocampus, whereas isoform 2 has been isolated from prostate. However,
      the regulation and characteristics of these isoforms are unknown. We identified
      the first three exons (1a, 1b, and 1c) by determining their transcription
      initiation sites. Exon 1b contained the initiation codon of isoform 2, and
      noncoding exons 1a and 1c contributed to isoform 1 mRNA. The dual luciferase
      promoter assay revealed three promoter regions, corresponding to the first exon
      of each isoform. Reverse transcription and PCR showed that exon 1a was expressed
      in the hippocampus, thalamus, and non-central nervous system (CNS) tissues,
      whereas exon 1b was detected only in non-CNS tissues. Exon 1c was observed in
      both CNS and non-CNS tissues, except for salivary glands. In vitro mutagenesis
      revealed that the initiation codon for isoform 2 in exon 1b was functional.
      Isoform 2 had additional hydrophilic amino acids at the amino terminal and was
      secreted from the neuroblastoma cell line Neuro2a. Isoform 1 fused with green
      fluorescent protein (GFP) was distributed to cellular processes, whereas isoform
      2-GFP was retained in the Golgi apparatus. We suggest that not only alternative
      splicing but also tissue-specific use of multiple promoters regulate the
      expression and intracellular trafficking of KLK11/hippostasin isoforms.

PMID- 16911519
TI  - The role of electrostatic interactions in the antitumor activity of dimeric
      RNases.
AB  - The cytotoxic action of some ribonucleases homologous to bovine pancreatic RNase
      A, the superfamily prototype, has interested and intrigued investigators. Their
      ribonucleolytic activity is essential for their cytotoxic action, and their
      target RNA is in the cytosol. It has been proposed that the cytosolic RNase
      inhibitor (cRI) plays a major role in determining the ability of an RNase to be
      cytotoxic. However, to interact with cRI RNases must reach the cytosol, and cross
      intracellular membranes. To investigate the interactions of cytotoxic RNases with
      membranes, cytotoxic dimeric RNases resistant, or considered to be resistant to
      cRI, were assayed for their effects on negatively charged membranes. Furthermore,
      we analyzed the electrostatic interaction energy of the RNases complexed in
      silico with a model membrane. The results of this study suggest that close
      correlations can be recognized between the cytotoxic action of a dimeric RNase
      and its ability to complex and destabilize negatively charged membranes.

PMID- 16911520
TI  - Interferon-alpha induces sensitization of cells to inhibition of protein
      synthesis by tumour necrosis factor-related apoptosis-inducing ligand.
AB  - Tumour cells are often sensitized by interferons to the effects of tumour
      necrosis factor-alpha-related apoptosis-inducing ligand (TRAIL). We have
      demonstrated previously that TRAIL has an inhibitory effect on protein synthesis
      [Jeffrey IW, Bushell M, Tilleray VJ, Morley S & Clemens MJ (2002) Cancer Res62,
      2272-2280] and we have therefore examined the consequences of prior interferon
      alpha treatment for the sensitivity of translation to inhibition by TRAIL.
      Interferon treatment alone has only a minor effect on protein synthesis but it
      sensitizes both MCF-7 cells and HeLa cells to the downregulation of translation
      by TRAIL. The inhibition of translation is characterized by increased
      phosphorylation of the alpha subunit of eukaryotic initiation factor eIF2 and
      dephosphorylation of the eIF4E-binding protein 4E-BP1. Both of these effects, as
      well as the decrease in overall protein synthesis, require caspase-8 activity,
      although they precede overt apoptosis by several hours. Interferon-alpha enhances
      the level and/or the extent of activation of caspase-8 by TRAIL, thus providing a
      likely explanation for the sensitization of cells to the inhibition of
      translation.

PMID- 16911521
TI  - Three mammalian cytochromes b561 are ascorbate-dependent ferrireductases.
AB  - Cytochromes b(561) are a family of transmembrane proteins found in most
      eukaryotic cells. Three evolutionarily closely related mammalian cytochromes
      b(561) (chromaffin granule cytochrome b, duodenal cytochrome b, and lysosomal
      cytochrome b) were expressed in a Saccharomyces cerevisiaeDeltafre1Deltafre2
      mutant, which lacks almost all of its plasma membrane ferrireductase activity, to
      study their ability to reduce ferric iron (Fe(3+)). The expression of each of
      these cytochromes b(561) was able to rescue the growth defect of the
      Deltafre1Deltafre2 mutant cells in iron-deficient conditions, suggesting their
      involvement in iron metabolism. Plasma membrane ferrireductase activities were
      measured using intact yeast cells. Each cytochrome b(561) showed significant FeCN
      and Fe(3+)-EDTA reductase activities that were dependent on the presence of
      intracellular ascorbate. Site-directed mutagenesis of lysosomal cytochrome b was
      conducted to identify amino acids that are indispensable for its activity. Among
      more than 20 conserved or partially conserved amino acids that were investigated,
      mutations of four His residues (H47, H83, H117 and H156), one Tyr (Y66) and one
      Arg (R67) completely abrogated the FeCN reductase activity, whereas mutations of
      Arg (R149), Phe (F44), Ser (S115), Trp (W119), Glu (E196), and Gln (Q131)
      affected the ferrireductase activity to some degree. These mutations may affect
      the heme coordination, ascorbate binding, and/or ferric substrate binding.
      Possible roles of these residues in lysosomal cytochrome b are discussed. This
      study demonstrates the ascorbate-dependent transmembrane ferrireductase
      activities of members of the mammalian cytochrome b(561) family of proteins.

PMID- 16911522
TI  - Role of asparagine 1134 in glucosidic bond and transglycosylation specificity of
      reuteransucrase from Lactobacillus reuteri 121.
AB  - Glucansucrases from lactic acid bacteria convert sucrose into various alpha
      glucans that differ greatly with respect to the glucosidic bonds present (e.g.
      dextran, mutan, alternan and reuteran). This study aimed to identify the
      structural features of the reuteransucrase from Lactobacillus reuteri 121 (GTFA)
      that determine its reaction specificity. We here report a detailed mutational
      analysis of a conserved region immediately next to the catalytic Asp1133
      (putative transition-state stabilizing) residue in GTFA. The data show that
      Asn1134 is the main determinant of glucosidic bond product specificity in this
      reuteransucrase. Furthermore, mutations at this position greatly influenced the
      hydrolysis/transglycosylation ratio. Changes in this amino acid expands the range
      of glucan and gluco-oligosaccharide products synthesized from sucrose by mutant
      GTFA enzymes.

PMID- 16911523
TI  - Role of transcription factor activator protein 1 (AP1) in epidermal growth factor
      mediated protection against apoptosis induced by a DNA-damaging agent.
AB  - We investigated the survival signals of epidermal growth factor (EGF) in human
      gastric adenocarcinoma cell line TMK-1. Treatment of TMK-1 cells with adriamycin
      (ADR) caused apoptosis and apoptosis-related reactions such as the release of
      cytochrome c from mitochondria and the activation of caspase 9. However, EGF
      treatment greatly reduced the ADR-induced apoptosis as well as these reactions.
      We previously reported that hepatocyte growth factor transmitted protective
      signals against ADR-induced apoptosis by causing activation of the
      phosphatidylinositol-3'-OH kinase (PtdIns3-K)/Akt signaling pathway in human
      epithelial cell line MKN74 [Takeuchi K & Ito F (2004) J Biol Chem279, 892-900].
      However, PtdIns3-K/Akt signaling did not mediate the antiapoptotic action of EGF
      in TMK-1 cells. EGF increased the expression of the Bcl-X(L) protein, an
      antiapoptotic member of the Bcl-2 family, but not that of other anti (Bcl-2) or
      proapoptotic (Bad and Bax) protein members. Expression of the c-Fos and c-Jun,
      components of activator protein 1 (AP1), which are known to regulate bcl-X(L)
      gene transcription, were increased in response to EGF. Pretreatment of the cells
      with PD98059, an inhibitor of MAP kinase kinase, inhibited the EGF-induced c-Fos
      and c-Jun expression, AP1 DNA binding, Bcl-X(L) expression, and the resistance
      against ADR-induced apoptosis, suggesting that EGF transmitted the antiapoptotic
      signal in such a way that it activated AP1 via a MAP kinase signaling pathway.
      TMK-1 cells stably transfected with TAM67, c-Jun dominant-negative mutant, did
      not display EGF-induced Bcl-X(L) expression or resistance against ADR-induced
      apoptosis. These results indicate that AP1-mediated upregulation of Bcl-X(L)
      expression is critical for protection of TMK-1 cells against ADR-induced
      apoptosis.

PMID- 16911524
TI  - Adenine nucleotides inhibit proliferation of the human lung adenocarcinoma cell
      line LXF-289 by activation of nuclear factor kappaB1 and mitogen-activated
      protein kinase pathways.
AB  - Extracellular nucleotides have a profound role in the regulation of the
      proliferation of diseased tissue. We studied how extracellular nucleotides
      regulate the proliferation of LXF-289 cells, the adenocarcinoma-derived cell line
      from human lung bronchial tumor. ATP and ADP strongly inhibited LXF-289 cell
      proliferation. The nucleotide potency profile was ATP = ADP = ATPgammaS > > UTP,
      UDP, whereas alpha,beta-methylene-ATP, beta,gamma-methylene-ATP, 2',3'-O-(4
      benzoylbenzoyl)-ATP, AMP and UMP were inactive. The nucleotide potency profile
      and the total blockade of the ATP-mediated inhibitory effect by the phospholipase
      C inhibitor U-73122 clearly show that P2Y receptors, but not P2X receptors,
      control LXF-289 cell proliferation. Treatment of proliferating LXF-289 cells with
      100 microm ATP or ADP induced significant reduction of cell number and massive
      accumulation of cells in the S phase. Arrest in S phase is also indicated by the
      enhancement of the antiproliferative effect of ATP by coapplication of the
      cytostatic drugs cisplatin, paclitaxel and etoposide. Inhibition of LXF-289 cell
      proliferation by ATP was completely reversed by inhibitors of extracellular
      signal related kinase-activating kinase/extracellular signal related kinase 1/2
      (PD98059, U0126), p38 mitogen-activated protein kinase (SB203508),
      phosphatidylinositol-3-kinase (wortmannin), and nuclear factor kappaB1 (SN50).
      Western blot analysis revealed transient activation of p38 mitogen-activated
      protein kinase, extracellular signal-related kinase 1/2, and nuclear factor
      kappaB1 and possibly new formation of p50 from its precursor p105. ATP-induced
      attenuation of LXF-289 cell proliferation was accompanied by transient
      translocation of p50 nuclear factor kappaB1 and extracellular signal-related
      kinase 1/2 to the nucleus in a similar time period. In summary, inhibition of LXF
      289 cell proliferation is mediated via P2Y receptors by activation of multiple
      mitogen-activated protein kinase pathways and nuclear factor kappaB1, arresting
      the cells in the S phase.

PMID- 16911525
TI  - Biochemical characterization of MelJ and MelK.
AB  - Melithiazol and myxothiazol are two myxobacterial metabolites that are highly
      efficient electron transport inhibitors of the respiratory chain. MelJ and MelK
      encoded in the melithiazol biosynthetic gene cluster were recently shown to be
      involved in the formation of the methyl ester from a hypothetical amide
      intermediate. In vivo studies suggest that the structurally highly similar amide
      myxothiazol A can be used as a substrate mimic of the hypothetical melithiazol
      amide to characterize the hydrolase MelJ. Both enzymes were produced in
      Escherichia coli as intein chitin fusion proteins and were purified using
      affinity chromatography. MelJ was found to catalyse the conversion of the amide
      myxothiazol to free myxothiazol acid. The formerly unknown myxothiazol acid was
      purified and used as a substrate for the methyl transferase MelK which methylates
      the compound using S-adenosyl-methionine as cosubstrate. Sequence analyses
      suggest that MelJ and MelK are members of the amidase signature family and of a
      new subclass of methyltransferases, respectively. Kinetic analyses point at a
      very high substrate specificity for both enzymes. Furthermore, the in vitro
      reconstitution of a unique mechanism of methyl ester formation found in
      myxobacteria is reported.

PMID- 16911526
TI  - Investigations into the ability of an oblique alpha-helical template to provide
      the basis for design of an antimicrobial anionic amphiphilic peptide.
AB  - AP1 (GEQGALAQFGEWL) was shown by theoretical analysis to be an anionic oblique
      orientated alpha-helix former. The peptide exhibited a monolayer surface area of
      1.42 nm(2), implying possession of alpha-helical structure at an air/water
      interface, and Fourier transform infrared spectroscopy (FTIR) showed the peptide
      to be alpha-helical (100%) in the presence of vesicle mimics of Escherichia coli
      membranes. FTIR lipid-phase transition analysis showed the peptide to induce
      large decreases in the fluidity of these E. coli membrane mimics, and Langmuir
      Blodgett trough analysis found the peptide to induce large surface pressure
      changes in monolayer mimics of E. coli membranes (4.6 mN.m(-1)). Analysis of
      compression isotherms based on mixing enthalpy (DeltaH) and the Gibbs free energy
      of mixing (DeltaG(Mix)) predicted that these monolayers were thermodynamically
      stable (DeltaH and DeltaG(Mix) each negative) but were destabilized by the
      presence of the peptide (DeltaH and DeltaG(Mix) each positive). The peptide was
      found to have a minimum lethal concentration of 3 mm against E. coli and was seen
      to cause lysis of erythrocytes at 5 mm. In combination, these data clearly show
      that AP1 functions as an anionic alpha-helical antimicrobial peptide and suggest
      that both its tilted peptide characteristics and the composition of its target
      membrane are important determinants of its efficacy of action.

PMID- 16911527
TI  - Functional association of the AAA complex and the peroxisomal importomer.
AB  - The AAA peroxins, Pex1p and Pex6p, are components of the peroxisomal protein
      import machinery required for the relocation of the import receptor Pex5p from
      the peroxisomal membrane to the cytosol. We demonstrate that Pex1p and Pex6p form
      a stable complex in the cytosol, which associates at the peroxisomal membrane
      with their membrane anchor Pex15p and the peroxisomal importomer. The
      interconnection of Pex15p with the components of the importomer was independent
      of Pex1p and Pex6p, indicating that Pex15p is an incorporated component of the
      assembly. Further evidence suggests that the AAA peroxins shuttle between cytosol
      and peroxisome with proper binding of the Pex15p-AAA complex to the importomer
      and release of the AAA peroxins from the peroxisomal membrane depending on an
      operative peroxisomal protein import mechanism. Pex4p-deficient cells exhibit a
      wild-type-like assembly of the importomer, which differs in that it is associated
      with increased amounts of Pex1p and Pex6p, in agreement with a function for Pex4p
      in the release of AAA peroxins from the peroxisomal membrane.

PMID- 16911528
TI  - The CssRS two-component regulatory system controls a general secretion stress
      response in Bacillus subtilis.
AB  - Bacillus species are valuable producers of industrial enzymes and
      biopharmaceuticals, because they can secrete large quantities of high-quality
      proteins directly into the growth medium. This requires the concerted action of
      quality control factors, such as folding catalysts and 'cleaning proteases'. The
      expression of two important cleaning proteases, HtrA and HtrB, of Bacillus
      subtilis is controlled by the CssRS two-component regulatory system. The induced
      CssRS-dependent expression of htrA and htrB has been defined as a protein
      secretion stress response, because it can be triggered by high-level production
      of secreted alpha-amylases. It was not known whether translocation of these alpha
      amylases across the membrane is required to trigger a secretion stress response
      or whether other secretory proteins can also activate this response. These
      studies show for the first time that the CssRS-dependent response is a general
      secretion stress response which can be triggered by both homologous and
      heterologous secretory proteins. As demonstrated by high-level production of a
      nontranslocated variant of the alpha-amylase, AmyQ, membrane translocation of
      secretory proteins is required to elicit this general protein secretion stress
      response. Studies with two other secretory reporter proteins, lipase A of B.
      subtilis and human interleukin-3, show that the intensity of the protein
      secretion stress response only partly reflects the production levels of the
      respective proteins. Importantly, degradation of human interleukin-3 by
      extracellular proteases has a major impact on the production level, but only a
      minor effect on the intensity of the secretion stress response.

PMID- 16911529
TI  - Iron regulatory protein-independent regulation of ferritin synthesis by nitrogen
      monoxide.
AB  - The discovery of iron-responsive elements (IREs), along with the identification
      of iron regulatory proteins (IRP1, IRP2), has provided a molecular basis for our
      current understanding of the remarkable post-transcriptional regulation of
      intracellular iron homeostasis. In iron-depleted conditions, IRPs bind to IREs
      present in the 5'-UTR of ferritin mRNA and the 3'-UTR of transferrin receptor
      (TfR) mRNA. Such binding blocks the translation of ferritin, the iron storage
      protein, and stabilizes TfR mRNA, whereas the opposite scenario develops when
      iron in the intracellular transit pool is plentiful. Nitrogen monoxide (commonly
      designated nitric oxide; NO), a gaseous molecule involved in numerous functions,
      is known to affect cellular iron metabolism via the IRP/IRE system. We previously
      demonstrated that the oxidized form of NO, NO(+), causes IRP2 degradation that is
      associated with an increase in ferritin synthesis [Kim, S & Ponka, P (2002) Proc
      Natl Acad Sci USA99, 12214-12219]. Here we report that sodium nitroprusside
      (SNP), an NO(+) donor, causes a dramatic and rapid increase in ferritin synthesis
      that initially occurs without changes in the RNA-binding activities of IRPs.
      Moreover, we demonstrate that the translational efficiency of ferritin mRNA is
      significantly higher in cells treated with SNP compared with those incubated with
      ferric ammonium citrate, an iron donor. Importantly, we also provide definitive
      evidence that the iron moiety of SNP is not responsible for such changes. These
      results indicate that SNP-mediated increase in ferritin synthesis is, in part,
      due to an IRP-independent and NO(+)-dependent post-transcriptional, regulatory
      mechanism.

PMID- 16911530
TI  - Structural insights into mechanisms of non-nucleoside drug resistance for HIV-1
      reverse transcriptases mutated at codons 101 or 138.
AB  - Lys101Glu is a drug resistance mutation in reverse transcriptase clinically
      observed in HIV-1 from infected patients treated with the non-nucleoside
      inhibitor (NNRTI) drugs nevirapine and efavirenz. In contrast to many NNRTI
      resistance mutations, Lys101(p66 subunit) is positioned at the surface of the
      NNRTI pocket where it interacts across the reverse transcriptase (RT) subunit
      interface with Glu138(p51 subunit). However, nevirapine contacts Lys101 and
      Glu138 only indirectly, via water molecules, thus the structural basis of drug
      resistance induced by Lys101Glu is unclear. We have determined crystal structures
      of RT(Glu138Lys) and RT(Lys101Glu) in complexes with nevirapine to 2.5 A,
      allowing the determination of water structure within the NNRTI-binding pocket,
      essential for an understanding of nevirapine binding. Both RT(Glu138Lys) and
      RT(Lys101Glu) have remarkably similar protein conformations to wild-type RT,
      except for significant movement of the mutated side-chains away from the NNRTI
      pocket induced by charge inversion. There are also small shifts in the position
      of nevirapine for both mutant structures which may influence ring stacking
      interactions with Tyr181. However, the reduction in hydrogen bonds in the drug
      water-side-chain network resulting from the mutated side-chain movement appears
      to be the most significant contribution to nevirapine resistance for
      RT(Lys101Glu). The movement of Glu101 away from the NNRTI pocket can also explain
      the resistance of RT(Lys101Glu) to efavirenz but in this case is due to a loss of
      side-chain contacts with the drug. RT(Lys101Glu) is thus a distinctive NNRTI
      resistance mutant in that it can give rise to both direct and indirect mechanisms
      of drug resistance, which are inhibitor-dependent.

PMID- 16911531
TI  - EcR expression in the prothoracicotropic hormone-producing neurosecretory cells
      of the Bombyx mori brain.
AB  - The steroid hormone 20-hydroxyecdysone (20E) initiates insect molting and
      metamorphosis through binding with a heterodimer of two nuclear receptors, the
      ecdysone receptor (EcR) and ultraspiracle (USP). Expression of the specific
      isoforms EcR-A and EcR-B1 governs steroid-induced responses in the developing
      cells of the silkworm Bombyx mori. Here, analysis of EcR-A and EcR-B1 expression
      during larval-pupal development showed that both genes were up-regulated by 20E
      in the B. mori brain. Whole-mount in situ hybridization and immunohistochemistry
      revealed that EcR-A and EcR-B1 mRNAs and proteins were exclusively located in two
      pairs of lateral neurosecretory cells in the larval brain known as the
      prothoracicotropic hormone (PTTH)- producing cells (PTPCs). In the pupal brain,
      EcR-A and EcR-B1 expression was detected in tritocerebral cells and optic lobe
      cells in addition to PTPCs. As PTTH controls ecdysone secretion by the
      prothoracic gland, these results indicate that 20E-responsive PTPCs are the
      master cells of insect metamorphosis.

PMID- 16911532
TI  - A review of causal factors and control measures for bloat in farmed salmonids
      with a suggested mechanism for the development of the condition.
AB  - A mechanism for the development of bloat in salmonids is proposed and explained
      in terms of the physiology of digestion and osmoregulation in fish. Understanding
      the causal factors for bloat enables control measures to be identified. In farmed
      salmonids, the chyme produced during the digestion of nutrient-rich pelleted
      foods that rapidly disintegrate in the stomach will be a potent activator of a
      negative feedback mechanism (enterogastric control), which slows stomach emptying
      to protect the small intestine from nutrient overload. In saline environments
      salmonids continuously drink sea water to replace fluid lost across the gills.
      Fluid loss is increased during periods of stress caused by factors such as low
      oxygen levels, elevated temperature or high salinity. When ingestion of nutrient
      rich food results in prolonged activation of enterogastric control, slowed
      stomach emptying leads to decreased absorption of water, thirst and increased
      drinking. This further exacerbates stomach distention. The proposed mechanism for
      the development of bloat is supported by on-farm experience where measures to
      control bloat include reducing food intake, altering the composition of the diet
      and using appropriate strategies to reduce stress.

PMID- 16911533
TI  - Microfauna associated with amoebic gill disease in sea-farmed Atlantic salmon,
      Salmo salar L., smolts.
AB  - A study of microfauna, associated with pathological changes in the gills of
      Atlantic salmon, Salmo salar L., was conducted over 2001-2002. Monthly samples of
      1(+) salmon smolts were taken, protozoan populations were quantified and gill
      health was assessed histologically. Protozoan densities were correlated with
      pathological changes, in order to determine their possible role in lesions in the
      gills. The most severe gill tissue changes were observed in summer/autumn and the
      least in spring. A diverse polyphyletic protozoan community was observed
      colonizing the gills, including Neoparamoeba sp., other amoebae, scuticociliates,
      Ichthyobodo-like flagellates, trichodinid ciliates and prostomatean ciliates. The
      earlier gill tissue changes in the gill were not always associated with the
      presence of these microorganisms, whereas amoebae (other than Neoparamoeba sp.),
      Ichthyobodo-like flagellates and trichodinid ciliates correlated with augmenting
      gill lesions. Neoparamoeba sp. was present, but its abundance did not correlate
      with the disease. This study suggests that a diversity of protozoans including
      Ichthyobodo-like flagellates, trichodinid ciliates and amoebae other than
      Neoparamoeba sp. are involved in the aetiology of amoebic gill disease in the
      Irish situation.

PMID- 16911534
TI  - High yield and rapid growth of Neoparamoeba pemaquidensis in co-culture with a
      rainbow trout gill-derived cell line RTgill-W1.
AB  - Neoparamoeba pemaquidensis is an ubiquitous amphizoic marine protozoan and has
      been implicated as the causative agent for several diseases in marine organisms,
      most notably amoebic gill disease (AGD) in Atlantic salmon. Despite several
      reports on the pathology of AGD, relatively little is known about the protozoan
      and its relationship to host cells. In this study, an in vitro approach using
      monolayers of a rainbow trout gill cell line (RTgill-W1, ATCC CRL-2523) was used
      to rapidly grow large numbers of N. pemaquidensis (ATCC 50172) and investigate
      cell-pathogen interactions. Established cell lines derived from other tissues of
      rainbow trout and other fish species were also evaluated for amoeba growth
      support. The amoebae showed preference and highest yield when grown with RTgill
      W1 over nine other tested fish cell lines. Amoeba yields could reach as high as 5
      x 10(5) cells mL(-1) within 3 days of growth on the gill cell monolayers. The
      amoebae caused visible focal lesions in RTgill-W1 monolayers within 24 h of
      exposure and rapidly proliferated and spread with cytopathic effects destroying
      the neighbouring pavement-like cells within 48-72 h after initial exposure in
      media above 700 mOsm kg(-1). Disruption of the integrity of the gill cell
      monolayers could be noted within 30 min of exposure to the amoeba suspensions by
      changes in transepithelial resistance (TER) compared with control cell monolayers
      maintained in the exposure media. This was significantly different by 2 h (P <
      0.05) compared with control cells and remained significantly different (P < 0.01)
      for the remaining 72 h that the TER was monitored. The RTgill-W1 cell line is
      thus a convenient model for growing N. pemaquidensis and for studying host
      pathogen interactions in AGD.

PMID- 16911535
TI  - A comparative study of susceptibility and induced pathology of cod, Gadus morhua
      (L.), and halibut, Hippoglossus hippoglossus (L.), following experimental
      infection with Moritella viscosa.
AB  - In this study experimental challenges with Moritella viscosa, the causative agent
      of winter ulcers in salmonids, were performed on juvenile Atlantic cod and
      Atlantic halibut. The challenges involved both intramuscular (i.m.) and
      intraperitoneal (i.p.) injections and bath with a strain originally isolated from
      Atlantic salmon. Cod was found to be significantly more sensitive than halibut to
      the infection. Both fish species were found to be more sensitive to i.m. than
      i.p. challenges. Both challenges induced a systemic disease in cod and halibut,
      but only cod was infected with an experimental bath challenge. Pathognomonic
      signs were found to be comparable with those described in M. viscosa-infected
      salmon and turbot. The main distinguishing pathological sign was that the cod
      showed host response to M. viscosa infection resulting in granuloma formation in
      infected tissues, which is a known response of cod to a infection with another
      Gram-negative bacterium, Aeromonas salmonicida. Re-isolation of M. viscosa from
      kidneys of cod and halibut with clear disease signs was problematic and
      optimization of isolation measures is needed. The results of this study indicate
      that M. viscosa infection may be a risk factor in cod farming, but that halibut
      is more resistant.

PMID- 16911536
TI  - Experimental infections with Lepeophtheirus salmonis (Kroyer) on threespine
      sticklebacks, Gasterosteus aculeatus L., and juvenile Pacific salmon,
      Oncorhynchus spp.
AB  - Experimental infections with Lepeophtheirus salmonis (Kroyer) were established on
      threespine sticklebacks, Gasterosteus aculeatus L., juvenile pink, Oncorhynchus
      gorbuscha (Walbaum), and chum, Oncorhynchus keta (Walbaum), salmon. The
      prevalence and abundance of infections were initially higher on sticklebacks than
      on either salmon species. The initial prevalence and intensity of infections on
      chum salmon were higher than those on pink salmon, and declined on both species
      during louse development. The rate of parasite development to adult stages was
      similar on all species although development beyond the preadult stage was not
      observed on sticklebacks. These results confirm previous field observations on
      the occurrence and development of L. salmonis on threespine sticklebacks.

PMID- 16911537
TI  - Differences in Ichthyophonus prevalence and infection severity between upper
      Yukon River and Tanana River chinook salmon, Oncorhynchus tshawytscha (Walbaum),
      stocks.
AB  - Two genetically distinct populations of chinook salmon, Oncorhynchus tshawytscha
      (Walbaum), were simultaneously sampled at the confluence of the Yukon and Tanana
      rivers in 2003. Upper Yukon-Canadian fish had significantly higher infection
      prevalence as well as more severe infections (higher parasite density in heart
      tissue) than the lower Yukon-Tanana River fish. Both populations had migrated the
      same distance from the mouth of the Yukon River at the time of sampling but had
      significantly different distances remaining to swim before reaching their
      respective spawning grounds. Multiple working hypotheses are proposed to explain
      the differences between the two stocks: (1) the two genetically distinct
      populations have different inherent resistance to infection, (2) genetically
      influenced differences in feeding behaviour resulted in temporal and/or spatial
      differences in exposure, (3) physiological differences resulting from different
      degrees of sexual maturity influenced the course of disease, and (4) the most
      severely infected Tanana River fish either died en route or fatigued and were
      unable to complete their migration to the Tanana River, thus leaving a population
      of apparently healthier fish.

PMID- 16911538
TI  - Isolation and identification of Shewanella alga and its pathogenic effects on
      post-larvae of abalone Haliotis diversicolor supertexta.

PMID- 16911543
TI  - Research degrees for medical graduates.

PMID- 16911544
TI  - Study of osteoporosis awareness, investigation and treatment of patients
      discharged from a tertiary public teaching hospital.
AB  - BACKGROUND: Patients with fragility fractures secondary to osteoporosis are at
      risk of recurrent fracture. Osteoporosis is often underrecognized and
      undertreated. We looked at the levels of awareness, investigation and treatment
      of patients with fracture. METHODS: The study group included patients admitted to
      a tertiary teaching hospital. Postal surveys were sent to female patients over 60
      years of age who had been identified in the hospital database as having
      International Classification of Diseases-10 codes for fracture and discharged
      between June 1997 and January 2002. The questionnaire had specific questions on
      the histories of the fractures, the risk factors, the awareness of osteoporosis,
      bone mineral density testing and the treatment for osteoporosis. RESULTS: Of 1584
      surveys posted, 366 valid questionnaires were returned. The median age of
      respondents was 81 years with a range of 60-99 years. Fifty-nine per cent
      reported one fracture, 41% two or more fractures and 65% reported a hip fracture.
      Forty-eight per cent of patients were aware that they had osteoporosis and 35%
      reported having a bone density performed. Thirty-seven per cent reported being on
      treatment for osteoporosis on discharge, with the majority being on treatment
      with calcium (34%). CONCLUSION: This postal survey of a high-risk patient group
      discharged from a tertiary hospital confirm the findings from other population
      based and hospital-based studies that a significant proportion of patients at
      risk of further fracture are not investigated or offered specific treatment for
      osteoporosis. Lack of awareness of underlying osteoporosis by both treating
      clinicians and patients is likely to be a major contributing factor.

PMID- 16911545
TI  - Value of B-type natriuretic peptide in diagnosing left ventricular dysfunction in
      dialysis-dependent patients.
AB  - BACKGROUND: B-type natriuretic peptide (BNP) is elevated in patients with end
      stage renal failure. The reported accuracy of BNP in diagnosing left ventricular
      dysfunction in these patients has been inconsistent. AIM: To investigate the
      diagnostic values of BNP for left ventricular dysfunction in patients undergoing
      haemodialysis for chronic renal failure. METHODS: We measured plasma BNP before
      and at 10 min and 3, 6 and 24 h after haemodialysis in 56 patients. RESULTS: The
      average plasma BNP before haemodialysis was 284 +/- 369 pg/mL, which was higher
      than that of healthy subjects (37 +/- 37 pg/mL; n = 32, P < 0.01). The average
      plasma BNP in patients with left ventricular dysfunction (n = 21) was
      substantially higher than that in those with normal ventricular function before
      and at 10 min and 3, 6 and 24 h after haemodialysis (P < 0.001). The area under
      the receiver operating characteristic curves was greater than 0.895 before and at
      the four time points after haemodialysis (P < 0.01). Using 152 pg/mL as a cut-off
      value, predialysis BNP has 81% sensitivity and 83% specificity in diagnosing left
      ventricular dysfunction in these patients. CONCLUSION: We concluded that plasma
      BNP offers a good sensitivity and specificity in diagnosing left ventricular
      dysfunction in patients with dialysis-dependent renal failure.

PMID- 16911547
TI  - Controlled trial of multidisciplinary care teams for acutely ill medical
      inpatients: enhanced multidisciplinary care.
AB  - BACKGROUND: Acute hospital general medicine services care for ageing complex
      patients, using the skills of a range of health-care providers. Evidence suggests
      that comprehensive early assessment and discharge planning may improve efficiency
      and outcomes of care in older medical patients. AIM: To enhance assessment,
      communication, care and discharge planning by restructuring consistent, patient
      centred multidisciplinary teams in a general medicine service. METHODS:
      Prospective controlled trial enrolling 1538 consecutive medical inpatients.
      Intervention units with additional allied health staff formed consistent
      multidisciplinary teams aligned with inpatient admitting units rather than wards;
      implemented improved communication processes for early information collection and
      sharing between disciplines; and specified shared explicit discharge goals.
      Control units continued traditional, referral-based multidisciplinary models with
      existing staffing levels. RESULTS: Access to allied health services was
      significantly enhanced. There was a trend to reduced index length of stay in the
      intervention units (7.3 days vs 7.8 days in control units, P = 0.18), with no
      change in 6-month readmissions. In-hospital mortality was reduced from 6.4 to
      3.9% (P = 0.03); less patients experienced functional decline in hospital (P =
      0.04) and patients' ratings of health status improved (P = 0.02). Additional
      staffing costs were balanced by potential bed-day savings. CONCLUSION: This model
      of enhanced multidisciplinary inpatient care has provided sustainable efficiency
      gains for the hospital and improved patient outcomes.

PMID- 16911548
TI  - Management of paediatric thyroid carcinoma: recent experience with recombinant
      human thyroid stimulating hormone in preparation for radioiodine therapy.
AB  - BACKGROUND: Thyroid carcinoma in children is rare and raises unique management
      issues. Although metastatic disease is more common in this age group, prognosis
      remains good with appropriate treatment. The aim of the study was to report
      recent experience in the management of differentiated thyroid carcinoma in
      children, especially in the use of radioiodine after recombinant human thyroid
      stimulating hormone (rhTSH) stimulation. METHODS: Eight patients, aged 5-17 years
      (five were boys) presented following total thyroidectomy for thyroid carcinoma
      between May 2003 and June 2005. Seven had papillary carcinoma and one had
      follicular carcinoma. Five had known lymph node metastases and one had pulmonary
      metastases at presentation. Four patients had previously received therapeutic
      irradiation for malignancy. All eight underwent diagnostic iodine scans, seven
      with rhTSH stimulation. Seven went on to receive radioiodine treatment as
      hospital inpatients, comanaged by the paediatric and nuclear medicine units. The
      dosage of 131I ranged from 1.5 to 3.7 x 10(9) Bq. All except one were prepared by
      rhTSH stimulation. RESULTS: Seven of eight patients had significant uptake in the
      neck on diagnostic scan and two had pulmonary abnormalities. Six of seven
      evaluable patients achieved complete thyroid ablation. Both patients with
      pulmonary abnormalities had scan resolution, although one of them only after a
      second radioiodine treatment. All patients had thyroxine replacement in doses to
      suppress TSH and all remain alive and well at time of carrying out this study.
      CONCLUSION: Optimal management of paediatric thyroid carcinoma necessitates a
      multidisciplinary approach. Radioiodine therapy under rhTSH is an effective and
      safe adjuvant treatment in this special subgroup.

PMID- 16911549
TI  - Giving and receiving of gifts between pharmaceutical companies and medical
      specialists in Australia.
AB  - BACKGROUND: This study investigated the 'gift-relationship' between
      pharmaceutical companies and doctors. METHODS: The study was based on a survey
      questionnaire of 823 medical specialists from across Australia. The aim of this
      study was to investigate gifts offered to medical specialists in Australia by
      pharmaceutical companies, financial support actively sought by medical
      specialists for activities other than research and to consider what is ethically
      appropriate. RESULTS: A high percentage of specialists received offers of food
      (96%), items for the office (94%), personal gifts (51%) and journals or textbooks
      (50%). Most specialists were invited to product launches, symposia or educational
      events (75-84%) and 52% received offers of travel to conferences. A high
      proportion of offers were accepted (66-79%) except invitations to product
      launches (49%), sponsored symposia (53%) and offers of travel that included
      partners (27%). Fifteen per cent of specialists requested financial support from
      pharmaceutical companies for activities and items, including conferences, travel,
      educational activities, salaries and donations to specific funds. The study
      outlined guidelines on gifts from pharmaceutical companies and differing
      standards applying to gifts and grants for travel. We found that, although most
      gifts and requests for support complied with professional and pharmaceutical
      industry guidelines, some--including personal gifts, tickets to sporting events,
      entertainment and travel expenses for specialists' partners--did not. CONCLUSION:
      To ensure that physicians' judgements are free from real or perceived influence
      from industry and to maintain public trust, we support a shift towards more
      conservative standards on gifts and support for travel evident in recent
      guidelines.

PMID- 16911550
TI  - Critical review of complementary therapies in haemato-oncology.
AB  - There is evidence of the increasing use of complementary and alternative medicine
      by Australians diagnosed with cancer. Given the increasing desire of cancer
      patients to use complementary and alternative medicine, it is important that
      clinicians have a good understanding of the evidence available in this field.
      This critical review aims to provide an overview of the current evidence
      pertaining to a range of complementary therapies that are used in a supportive
      role in the treatment of cancer patients. Treatment methods considered are
      acupuncture, music therapy, massage and touch therapies and psychological
      interventions. The efficacy of these complementary therapies in terms of
      improvement in symptoms and quality of life is examined. Evidence that relates to
      an effect on immune function and survival is also investigated.

PMID- 16911551
TI  - Cautionary tales in the interpretation of systematic reviews of therapy trials.
AB  - This is the second in a series of articles emphasizing the cautions in the
      interpretation of health-care studies. Systematic reviews are presented as
      comprehensive, unbiased summaries of evidence and are often referred to by
      clinicians, guideline developers and health policy-makers. Their strengths and
      limitations, and how their results can be subject to bias and misinterpretation,
      are discussed.

PMID- 16911552
TI  - Zoledronic acid prevents bone loss after allogeneic haemopoietic stem cell
      transplantation.
AB  - Allogeneic haemopoietic stem cell transplant (alloHSCT) patients are at increased
      risk of osteoporosis. Zoledronic acid (ZA) is a potent i.v. bisphosphonate;
      however, there are few data on ZA use after alloHSCT. The aim of this study is to
      examine the effect of a single 4 mg ZA infusion in alloHSCT patients with either
      osteoporosis (T-score < -2.5) or rapid bone loss post-alloHSCT. An uncontrolled,
      prospective study of 12 consecutive patients receiving ZA, predominantly within
      the first year post-HSCT. Bone mineral density (BMD) was measured by dual-energy
      X-ray absorptiometry at the spine and proximal femur pretransplant, pre-ZA and
      post-ZA. The median annualized percentage change in total hip BMD between the
      pretransplant scan and the scan immediately before ZA was -13% (range, -51 to
      +3.6%). After ZA treatment, the total hip BMD increased by a median of +3.3%
      (range, -20.4 to +14.8%) in 75% of patients. The median annualized percentage
      change in femoral neck BMD between the pretransplant scan and the scan
      immediately before ZA was -13.2% (range, -40 to +1.0%). Post-ZA, femoral neck BMD
      increased by a median of +1.4% (range, -22.2 to +33.6%). Only one patient
      continued to lose bone from the femoral neck post-ZA infusion. The median
      annualized percentage change in spinal BMD pretransplant was -12.5% (range, -38
      to +6.9%). Post-ZA, spinal BMD decreased by a median of -2.8% (range, -27.6 to
      +24.4%). Four patients continued to lose bone from the spine post-ZA. ZA reduces
      bone loss in most patients after alloHSCT. Our data require confirmation in a
      larger prospective, randomized study.

PMID- 16911553
TI  - Phaeochromocytoma in pregnancy.
AB  - Hypertension during pregnancy is a common problem, causing significant maternal
      and fetal morbidity and mortality. Pre-eclampsia is by far the most common cause,
      affecting 5-10% of primigravid women. Phaeochromocytoma is a rare endocrine
      tumour causing hypersecretion of noradrenaline, adrenaline and/or dopamine. It is
      extremely rare during pregnancy and may be misdiagnosed with potentially
      catastrophic consequences. Delayed diagnosis remains a significant source of
      maternal and fetal morbidity and mortality. Recognition is critical, as the
      majority of maternal deaths have occurred when the diagnosis has been overlooked.
      Diagnosis of phaeochromocytoma is achieved by detecting increased catecholamines
      and metabolites (metanephrine and normetanephrine) on 24-h urine collection, as
      these levels are unaffected by pregnancy or pre-eclampsia. Definitive treatment
      of phaeochromocytoma is surgical and the laparoscopic approach has been shown to
      be safe and is preferred for most phaeochromocytomas. Medical preparation and
      treatment of hypertension is essential for safe surgery. Timing of adrenalectomy
      is either during the second trimester or as a staged procedure after Caesarean
      section delivery.

PMID- 16911554
TI  - Screening for colorectal cancer by faecal occult blood test: why people choose to
      refuse.
AB  - To better understand the personal barriers that limit participation in faecal
      occult blood test (FOBT) screening for colorectal cancer, non-participants from a
      recent screening initiative were sent detailed questionnaires, defining their
      reasons for not participating, as well as how to make screening more attractive.
      The important barrier was procrastination. The type of FOBT kit offered
      influenced the reasons for not participating. Convenient FOBT and greater general
      practitioner involvement may be important for optimizing community acceptance of
      FOBT-based screening.

PMID- 16911555
TI  - Dementia in a case of Behcet's disease.

PMID- 16911556
TI  - Sister Mary Joseph nodule: an important sign of an ominous diagnosis.

PMID- 16911557
TI  - Fluoroscopic evidence of prosthetic valve failure.

PMID- 16911558
TI  - Case of rifampicin-induced acute generalized exanthematous pustulosis.

PMID- 16911559
TI  - Analogies in medicine: the rare paradigm of the Maltese (white) cross.

PMID- 16911560
TI  - Diffuse alveolar haemorrhage in a young male smoker: a word of caution.

PMID- 16911562
TI  - p16INK4A is a robust in vivo biomarker of cellular aging in human skin.
AB  - The cell-cycle regulating gene, p16INK4A, encoding an inhibitor of cyclin
      dependent kinases 4 and 6, is considered to play an important role in cellular
      aging and in premature senescence. Although there is an age-dependent increase of
      p16INK4A expression in human fibroblast senescence in vitro, no data are
      available regarding the age dependency of p16INK4A in vivo. To determine whether
      p16INK4A expression in human skin correlates with donor age, p16INK4A expression
      was analyzed by immunohistochemistry as well as the expression of the p16INK4A
      repressor BMI1. Samples from the age groups 0-20, 21-70, and 71-95 years were
      selected from a bank of healthy human skin. We show that the number of p16INK4A
      positive cells is significantly higher in elderly individuals compared to the
      younger age groups. The number of p16INK4A positive cells was found to be
      increased in both epidermis and dermis, compartments with strictly different
      proliferative activities. BMI1 gene expression was significantly down-regulated
      with increasing donor age, whereas no striking age differences were observed for
      Ki67. In immunofluorescence co-expression studies, Ki67-positive cells were
      negative for p16INK4A and BMI1-expressing cells also stained negatively for Ki67.
      In conclusion, we provide for the first time evidence that p16INK4A expression
      directly correlates with chronological aging of human skin in vivo. p16INK4A
      therefore is a biomarker for human aging in vivo. The data reported here suggest
      a model for changes in regulatory gene expression that drive aging in human skin.

PMID- 16911565
TI  - 2B or not 2B? Differential identification of type 2B, versus pseudo-von
      Willebrand disease.

PMID- 16911563
TI  - Aging is associated with increased clonogenic potential in rat liver in vivo.
AB  - Cancer increases with age and often arises from the selective clonal growth of
      altered cells. Thus, any environment favoring clonal growth per se poses a higher
      risk for cancer development. Using a genetically tagged animal model, we
      investigated whether aging is associated with increased clonogenic potential.
      Groups of 4-, 12-, 18-, and 24-month-old Fischer 344 rats were infused (via the
      portal vein) with 2x10(6) hepatocytes isolated from a normal syngenic 2-month-old
      donor. Animals deficient in dipeptidyl-peptidase type IV (DPP-IV-) enzyme were
      used as recipients, allowing for the histochemical detection of injected DPP-IV+
      cells. Groups of animals were sacrificed at various times thereafter. No growth
      of DPP-IV+ transplanted hepatocytes was present after either 2 or 6 months in the
      liver of rats transplanted at young age, as expected. In striking contrast,
      significant expansion of donor-derived cells was seen in animals transplanted at
      the age of 18 months: clusters comprising 7-10 DPP-IV+ hepatocytes/cross-section
      were present after 2 months and were markedly enlarged after 6 months (mean of
      88+/-35 cells/cluster/cross-section). These results indicate that the
      microenvironment of the aged liver supports the clonal expansion of transplanted
      normal hepatocytes. Such clonogenic environments can foster the selective growth
      of pre-existing altered cells, thereby increasing the overall risk for cancer
      development associated with aging.

PMID- 16911566
TI  - Anti-apoptotic signalling by the Dot/Icm secretion system of L. pneumophila.
AB  - The Dot/Icm type IV secretion system of Legionella pneumophila triggers robust
      activation of caspase-3 during early and exponential stages of proliferation
      within human macrophages, but apoptosis is delayed till late stages of infection,
      which is novel. As caspase-3 is the executioner of the cell, we tested the
      hypothesis that L. pneumophila triggers anti-apoptotic signalling within the
      infected human macrophages to halt caspase-3 from dismantling the cells. Here we
      show that during early and exponential replication, L. pneumophila-infected human
      monocyte-derived macrophages (hMDMs) exhibit a remarkable resistance to induction
      of apoptosis, in a Dot/Icm-dependent manner. Microarray analyses and real-time
      PCR reveal that during exponential intracellular replication, L. pneumophila
      triggers upregulation of 12 anti-apoptotic genes that are linked to activation of
      the nuclear transcription factor kappa-B (NF-kappaB). Our data show that L.
      pneumophila induces a Dot/Icm-dependent sustained nuclear translocation of the
      p50 and p65 subunits of NF-kappaB during exponential intracellular replication.
      Bacterial entry is essential both for the anti-apoptotic phenotype of infected
      hMDMs and for nuclear translocation of the p65. Using p65-/- and IKKalpha-/- beta
      /- double knockout mouse embryonic fibroblast cell lines, we show that nuclear
      translocation of NF-kappaB is required for the resistance of L. pneumophila
      infected cells to apoptosis-inducing agents. In addition, the L. pneumophila
      induced nuclear translocation of NF-kappaB requires the activity of IKKalpha
      and/or IKKbeta. We conclude that although the Dot/Icm secretion system of L.
      pneumophila elicits an early robust activation of caspase-3 in human macrophages,
      it triggers a strong anti-apoptotic signalling cascade mediated, at least in part
      by NF-kappaB, which renders the cells refractory to external potent apoptotic
      stimuli.

PMID- 16911567
TI  - Nomadic or sessile: can Kupffer cells function as portals for malaria sporozoites
      to the liver?
AB  - The initial site of replication for Plasmodium parasites in mammalian hosts are
      hepatocytes, cells that offer unique advantages for the extensive parasite
      replication occurring prior to the erythrocytic phase of the life cycle. The
      liver is the metabolic centre of the body and has an unusual relationship to the
      immune system. However, to reach hepatocytes, sporozoites must cross the
      sinusoidal barrier, composed of specialized endothelia and Kupffer cells, the
      resident macrophages of the liver. Mounting evidence suggests that, instead of
      taking what would seem a safer route through endothelia, the parasites traverse
      Kupffer cells yet suffer no harm. Kupffer cells have a broad range of responses
      towards incoming microorganisms, toxins and antigens which depend on the nature
      of the intruder, the experimental conditions and the environmental circumstances.
      Kupffer cells may become activated or remain anergic, produce pro- or anti
      inflammatory mediators. Consequently, outcomes are diverse and include
      development of immunity or tolerance, parenchymal necrosis or regeneration,
      chronic cirrhotic transformation or acute liver failure. Here we review data
      concerning the unique structural and functional characteristics of Kupffer cells
      and their interactions with Plasmodium sporozoites in the context of a model in
      which these hepatic macrophages function as the sporozoite gate to the liver.

PMID- 16911568
TI  - The influence of diabetes on gingival crevicular fluid beta-glucuronidase and
      interleukin-8.
AB  - OBJECTIVES: Polymorphonuclear neutrophil (PMN) dysfunction is associated with
      diabetes. We examined the gingival crevicular fluid (GCF) beta-glucuronidase (BG)
      and interleukin-8 (IL-8) levels of periodontitis patients with and without type 2
      diabetes mellitus (DM). MATERIAL AND METHODS: Forty five adults with type 2 DM
      and 32 adults without DM, both with chronic periodontitis were enrolled. GCF was
      collected from eight posterior sites in each quadrant, and periodontal parameters
      were recorded. GCF was assayed for IL-8 by ELISA and BG by a fluorometric assay.
      RESULTS: GCF IL-8 was positively correlated with probing depth (PD), and GCF BG
      but not clinical attachment level (CAL), bleeding on probing (BOP), or plaque
      index (PI). In contrast, GCF BG was strongly correlated with each of the clinical
      measures of periodontal disease. Subjects with DM significantly lower levels of
      both BG (73.0+/-44.8 versus 121.9+/-84.6 pg/sample; p=0.002) and IL-8 (32.1+/
      33.1 versus 90.8+/-83.2 pg/sample; p<0.0001) even after adjustments for age,
      gender, PD, CAL, BOP, and PI. Neither BG nor IL-8 was correlated with HbA1c
      levels in subjects with DM. CONCLUSION: These data suggest that an inadequate
      local response by PMN, partially explained by an altered chemokine gradient, may
      contribute to periodontal disease in patients with type 2 DM.

PMID- 16911569
TI  - No correlation of five gene polymorphisms with periodontal conditions in a Greek
      population.
AB  - BACKGROUND: Various studies have examined possible correlations between a number
      of cytokine gene polymorphisms and periodontal disease in populations of
      different origins. The present study sought the correlation between four single
      nucleotide polymorphisms (IL1A+3954, IL1B+4845, TNFA-308, COL1A1 Sp1), a variable
      number of tandem repeats polymorphism (IL1RN intron 2) and periodontal conditions
      in subjects of Greek origin. METHODS: One hundred and ninety-two healthy
      subjects, stratified as non-periodontitis and periodontitis (chronic and
      aggressive) cases, participated in the present study. Genotyping was performed by
      polymerase chain reaction-based techniques using the primers and conditions
      described in the literature. The frequencies of genotypes between study groups
      were compared using Genepop v3.3 genetic software and Instat statistical package.
      RESULTS: No differences were observed among the groups concerning the
      distributions of genotypes under investigation. CONCLUSIONS: Carriage rates of
      the polymorphisms under investigation in systemically healthy subjects of Greek
      origin are well within the range reported for Caucasians but these polymorphisms
      cannot discriminate between non-periodontitis and periodontitis (chronic or
      aggressive) cases.

PMID- 16911570
TI  - The long-term results of diltiazem treatment for anal fissure.
AB  - The effects of diltiazem treatment on symptoms of chronic anal fissures and their
      long-term outcome were investigated. One hundred and twelve patients were
      supplied with 6-week course of 2% diltiazem cream for twice-daily topical
      application. The medical notes and extended follow-up by telephone for 112
      patients were recorded and statistically analysed. The success rate and
      satisfaction of topical diltiazem were each over two thirds. Nearly 80% of
      patients reported no adverse effects, and it seems that those complaints
      attributed to diltiazem rarely led to reduced compliance. After diltiazem therapy
      for fissure, 59% of patients required further treatment (medical and/or surgical)
      over the average 2-year period of follow-up. The reported adverse effects of
      topical diltiazem treatment in patients with anal fissures were more common than
      previously thought, although compliance was rarely affected. During consultation
      regarding the advantages and disadvantages of surgical vs. chemical
      sphincterotomy, patients should be aware that the majority of patients receiving
      diltiazem as the primary treatment for anal fissure subsequently require further
      treatment.

PMID- 16911571
TI  - Adjuvant chemotherapy in non-small cell lung cancer.
AB  - Adjuvant chemotherapy is considered a standard of care for many malignancies, the
      most well known being breast and colon cancer. Unfortunately, less than a third
      of patients with non-small cell lung cancer (NSCLC) present with resectable
      disease and despite resection outcomes are often poor with a median 5-year
      survival of 40-50%. Modern chemotherapy for NSCLC provides both a survival
      advantage and an improvement in quality of life in the palliative setting.
      Several large studies using modern platinum-based regimens have been presented
      since the 1995 meta-analysis. This demonstrated a nonsignificant benefit for
      older platinum-based regiments. These studies have consistently shown a survival
      benefit across all stages of resection with acceptable toxicity. The absolute
      magnitude of benefit is consistent with that achieved in other malignancies where
      adjuvant chemotherapy is offered as a standard of care.

PMID- 16911572
TI  - The management of PS2 patients with advanced non-small cell lung cancer.
AB  - Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths
      in the Western world. Patients with impaired performance status (PS2 or greater)
      have both worse prognosis and toxicity from treatment in general. The median
      survival of PS2 patients with advanced NSCLC is 4-5 months in comparison with the
      8-9 months expected for those with good performance status (PS0-1). PS2
      represents 30%-40% of all patients with advanced NSCLC, and their management
      remains controversial. In general, they have been excluded from most clinical
      trials. The emphasis on treatment should be on maintenance and improvement of
      quality of life with treatment strategies that provide rapid clinical
      improvement.

PMID- 16911573
TI  - Influence of climate on the incidence of thiazide-induced hyponatraemia.
AB  - The role of hot temperature has been implicated in thiazide-induced
      hyponatraemia; however, it has never been studied in a systematic manner. The aim
      of this retrospective study is to correlate the incidence of thiazide-induced
      hyponatraemia and climate factors in a university teaching hospital from June
      1996 to February 2002. We evaluated a representative sample of 201 subjects with
      thiazide-induced hyponatraemia. Overall, 2.9 +/- 2.2 (range 0-10, median 3) cases
      of thiazide-induced hyponatraemia were encountered each month during the study
      period. There was no seasonal variation in the rate of thiazide-induced
      hyponatraemia (overall chi(2) test, p = 7.0). Thiazide-induced hyponatraemia was
      not more frequently reported in summer. There was no discernible correlation
      between the monthly number of cases and average air temperature (r = -0.056, p =
      0.65) and relative humidity (r = 0.103, p = 0.40). On the other hand, patients
      who presented with thiazide-induced hyponatraemia in July and August had
      significantly higher serum sodium concentration, 118 +/- 7 mmol/l vs. 114 +/- 8
      mmol/l in other calendar months (p = 0.016). Temperature showed a statistically
      significant positive correlation with the level of serum sodium (r = 0.20, p =
      0.004). These data demonstrate that there are no seasonal variations in thiazide
      induced hyponatraemia disorders, at least in countries with subtropical climate.
      The question arises whether hypotonic sweat loss mitigates the risk of excessive
      water drinking in hot summer.

PMID- 16911574
TI  - Surgical treatment of malignant carcinoid tumours of the appendix.
AB  - Since their first description in 1882, malignant neoplasms of the appendix still
      remain rare. Malignant carcinoid tumours are the most common accounting for 85%
      of all appendiceal neoplasms. Preoperative diagnosis is invariably difficult, and
      precise treatment protocols for these neoplasms remain unclear. We reviewed our
      experience and searched published evidence to produce management guidelines. A
      retrospective review of all malignant carcinoid tumours diagnosed in our hospital
      between April 1994 and December 2003 was performed. Patient demographics,
      operative details, histological types and clinical outcomes were retrieved from
      case notes supplemented by a questionnaire to the patient's General Practitioner.
      A literature search was then performed. Nine patients were identified with
      classical carcinoid tumours (CCT); (M = 3 and F = 6, mean age: 43, range 14-81)
      and two patients with goblet-cell morphology (F = 2, age 46 and 76). Mean follow
      up was 63 months (range 1-125 months). Nine patients were alive at the end of
      follow-up. Appendicectomy was performed for acute appendicitis. Other appendiceal
      pathologies were identified following hemicolectomy and oophorectomy. CCT are the
      most common tumours and have the better prognosis. From our experience and
      subsequent review of the literature, we recommend right hemicolectomy as the
      treatment of choice for malignant carcinoid tumours. However, small CCTs less
      than 2 cm in diameter at the tip of the appendix, with a low proliferative index,
      without angiolymphatic or mesoappendiceal extension can be treated by
      appendicectomy. Following oncological assessment, further adjuvant therapy should
      be considered for patients with advanced disease.

PMID- 16911575
TI  - Gout Assessment Questionnaire: Initial results of reliability, validity and
      responsiveness.
AB  - We evaluated the psychometric properties of a new gout-specific patient reported
      outcomes questionnaire. The Gout Assessment Questionnaire (GAQ) and the SF-36
      were administered to 126 subjects in a multicenter Phase II program of
      febuxostat, an investigational treatment for hyperuricemia (serum uric acid >8.0
      mg/dl) in patients with chronic gout. The questionnaire was administered at
      baseline and 1, 6 and 12 months later. The majority of subjects, mean age 54
      years, were male, Caucasian and had experienced a gout flare within the last
      year. Seven domains were identified, all met criteria for reliability and
      validity. Cronbach's alpha ranged from 0.78 to 0.97. Pearson correlations between
      GAQ and SF-36 scales were generally low to moderate, with the highest correlation
      between Gout Pain and Severity and SF-36 Bodily Pain, r = 0.45. Guyatt's
      statistic (measure of responsiveness) ranged from 0.24 to 1.00 at 12 months.
      Minimal clinically important differences ranged from 2 (Gout Concern) to 10
      points (Productivity). The GAQ has acceptable psychometric properties. Further
      research is required to confirm results, which may provide more information to
      improve the GAQ for use in clinical trials.

PMID- 16911576
TI  - New perspectives on the role of autonomic nervous system in the genesis of
      arrhythmias.
AB  - Sudden cardiac death (SCD) is a major cause of morbidity and mortality in
      patients with coronary artery diseases and myocardial infarction (MI). There is a
      circadian variation of the frequency of SCD. Beta-blocker therapy significantly
      reduces the incidence of SCD after MI. These clinical observations suggest a
      close association between ventricular arrhythmia and sympathetic activity in
      patients with MI. Following injury, peripheral nerves undergo Wallerian
      degeneration, which may be followed by neurilemma cell proliferation and axonal
      regeneration (nerve sprouting), resulting in sympathetic hyperinnervation. It is
      possible that the increased innervation after myocardial injury may result in
      increased sympathetic nerve density, which in turn increases the propensity for
      cardiac arrhythmia. While this Nerve Sprouting Hypothesis seemed to be intuitive,
      there was no experimental proof of a causal link between sympathetic nerve
      sprouting and arrhythmogenesis. We therefore performed several studies to
      determine the relationship between nerve sprouting and cardiac arrhythmia. We
      also performed direct sympathetic nerve recording in an animal model of SCD. We
      found that cardiac sympathetic nerves are highly plastic. In addition to MI and
      rapid pacing, nerve sprouting and heterogeneous sympathetic hyperinnervation may
      also be induced by radiofrequency ablation, hypercholesterolemia, and stem cells
      transplantation. The coexistence of denervated and hyperinnervated area in the
      diseased myocardium could result in increased electrophysiological heterogeneity
      during sympathetic activation, leading to ventricular arrhythmia and SCD.

PMID- 16911577
TI  - Ablation of atrial fibrillation in humans using a balloon-based ablation system:
      identification of the site of phrenic nerve damage using pacing maneuvers and
      CARTO.
AB  - Injury of the phrenic nerve during pulmonary vein isolation for the treatment of
      atrial fibrillation is a well-recognized complication, especially when performing
      ostial ablations or using balloon-based technologies. This report describes the
      exact anatomical location of phrenic nerve injury during an attempt of right
      superior pulmonary vein isolation using a balloon that delivered high intensity
      focused ultrasound. Electroanatomical three-dimensional CARTO (Biosense Webster,
      Diamond Bar, CA, USA) mapping of the superior caval vein, the right and left
      atrium, as well as the right superior pulmonary vein was performed in conjunction
      with meticulous phrenic nerve pacing maneuvers before and after ablation and
      showed that the nerve was damaged at the level of the antero-inferior ostium of
      the right superior pulmonary vein. Diaphragmatic denervation occurred despite
      using an oversized balloon fluoroscopically placed at the atrial side of the
      pulmonary vein ostium.

PMID- 16911578
TI  - Clinical course and risk stratification of patients affected with the Jervell and
      Lange-Nielsen syndrome.
AB  - INTRODUCTION: Data regarding risk factors and clinical course of patients
      affected with Jervell and Lange-Nielsen syndrome (JLNS), an autosomal recessive
      form of the congenital long-QT syndrome (LQTS), are limited to several reported
      cases and a retrospective analysis. METHODS AND RESULTS: We prospectively
      followed-up 44 JLNS patients from the U.S. portion of the International LQTS
      Registry and compared their clinical course with 2,174 patients with the
      phenotypically determined dominant form of LQTS (Romano-Ward syndrome [RWS]) and
      a subgroup of 285 patients with type 1 LQTS (LQT1). Mean (+/-SD) corrected QT
      interval (QTc) in the JLNS, RWS, and LQT1 groups were 548 +/- 73, 500 +/- 48, and
      502 +/- 46 msec, respectively (P < 0.001). The cumulative rates of cardiac events
      from birth through age 40 among JLNS and RWS patients were 93% (mean [+/-SD] age:
      5.0 +/- 7.0 years) and 54% (mean [+/-SD] age: 14.2 +/- 9.3 years), respectively
      (P < 0.001). The JLNS:RWS and JLNS:LQT1 adjusted hazard ratios (HR) for cardiac
      events were highest among patients with a baseline QTc > or = 550 msec (HR =
      15.83 [P < 0.001] and 13.80 [P < 0.001], respectively). Among JLNS patients
      treated with beta-blockers, the cumulative probability of LQTS-related death was
      35%; defibrillator therapy was associated with a 0% mortality rate during a mean
      (+/-SD) follow-up period of 4.9 +/- 3.4 years. CONCLUSIONS: Patients with JLNS
      experience a high rate of cardiac and fatal events from early childhood despite
      medical therapy. Defibrillator therapy appears to improve outcome in this high
      risk population, although longer follow-up is needed to establish its long-term
      efficacy.

PMID- 16911579
TI  - Characterization of conduction recovery across left atrial linear lesions in
      patients with paroxysmal and persistent atrial fibrillation.
AB  - BACKGROUND: Left atrial (LA) linear lesions are effective in substrate
      modification for atrial fibrillation (AF). However, achievement of complete
      conduction block remains challenging and conduction recovery is commonly
      observed. The aim of the study was to investigate the localization of gap sites
      of recovered LA linear lesions. METHODS AND RESULTS: Forty-eight patients with
      paroxysmal (n = 26) and persistent/permanent (n = 22) AF underwent repeat
      ablation after pulmonary vein (PV) isolation and LA linear ablation at the LA
      roof and/or mitral isthmus due to recurrences of AF or flutter. In 35 patients,
      conduction through the mitral isthmus line (ML) had recovered whereas roof-line
      recovery was observed in 30 patients. The gaps within the ML were distributed to
      the junction between left inferior PV and left atrial appendage in 66%, the
      middle part of the ML in 20%, and in 8% to the endocardial aspect of the ML while
      only 6% of lines showed an epicardial site of recovery. The RL predominantly
      recovered close to the right superior PV (54%) and less frequently in the mid
      roof or close to the left PV (both 23%). Reablation of lines required
      significantly shorter RF durations (ML: 7.24 +/- 5.55 minutes vs 24.08 +/- 9.38
      minutes, RL: 4.24 +/- 2.34 minutes vs 11.54 +/- 6.49 minutes; P = 0.0001).
      Patients with persistent/permanent AF demonstrated a significantly longer
      conduction delay circumventing the complete lines than patients with paroxysmal
      AF (228 +/- 77 ms vs 164 +/- 36 ms, P = 0.001). CONCLUSIONS: Gaps in recovered LA
      lines were predominantly located close to the PVs where catheter stability is
      often difficult to achieve. Shorter RF durations are required for reablation of
      recovered linear lesions. Conduction times around complete LA lines are
      significantly longer in patients with persistent/permanent AF as compared to
      patients with paroxysmal AF.

PMID- 16911580
TI  - Stimulation of excitatory amino acid release from adult mouse brain glia
      subcellular particles by high mobility group box 1 protein.
AB  - The multifunctional protein high mobility group box 1 (HMGB1) is expressed in
      hippocampus and cerebellum of adult mouse brain. Our aim was to determine whether
      HMGB1 affects glutamatergic transmission by monitoring neurotransmitter release
      from glial (gliosomes) and neuronal (synaptosomes) re-sealed subcellular
      particles isolated from cerebellum and hippocampus. HMGB1 induced release of the
      glutamate analogue [(3)H]d-aspartate form gliosomes in a concentration-dependent
      manner, whereas nerve terminals were insensitive to the protein. The HMGB1-evoked
      release of [(3)H]d-aspartate was independent of modifications of cytosolic Ca(2+)
      , but it was blocked by dl-threo-beta-benzyloxyaspartate (dl-TBOA), an inhibitor
      of glutamate transporters. HMGB1 also stimulated the release of endogenous
      glutamate in a Ca(2+)-independent and dl-TBOA-sensitive manner. These findings
      suggest the involvement of carrier-mediated release. Moreover, dihydrokainic
      acid, a selective inhibitor of glutamate transporter 1 (GLT1), does not block the
      effect of HMGB1, indicating a role for the glial glutamate-aspartate transporter
      (GLAST) subtype in this response. We also demonstrate that HMGB1/glial particles
      association is promoted by Ca(2+). Furthermore, although HMGB1 can physically
      interact with GLAST and the receptor for advanced glycation end products (RAGE),
      only its binding with RAGE is promoted by Ca(2+). These results suggest that the
      HMGB1 cytokine could act as a modulator of glutamate homeostasis in adult mammal
      brain.

PMID- 16911581
TI  - The WT1 Wilms' tumor suppressor gene is a downstream target for insulin-like
      growth factor-I (IGF-I) action in PC12 cells.
AB  - The biological actions of the insulin-like growth factors, IGF-I and IGF-II, are
      mediated by the ligand-induced activation of the IGF-I receptor (IGF-IR), a
      transmembrane heterotetramer linked to the ras-raf-mitogen-activated protein
      kinase (MAPK) and phosphatidyl inositol 3 kinase (PI3K)-protein kinase B
      (PKB)/Akt signal transduction cascades. The Wilms' tumor suppressor gene (wt1)
      encodes a zinc finger transcription factor, WT1, which has been implicated in
      various cellular processes including proliferation, differentiation and
      apoptosis. In the present study we demonstrated that IGF-I modulates the WT1 gene
      expression in neurally derived PC12 cells in a dose- and time-dependent manner.
      This effect was mediated through both the MAPK and PI3-kinase signaling pathways,
      as shown by the ability of the specific inhibitors UO126 and LY294002 to abrogate
      IGF-I action. Moreover, using RT-PCR and transient transfection assays, we
      demonstrated that the IGF-I effect was associated with corresponding changes in
      WT1 mRNA levels and WT1 promoter activity. In addition, the results of the
      present study revealed that high WT1 levels were associated with the induction of
      apoptosis, whereas low WT1 levels were correlated with the inhibition of
      apoptosis, as demonstrated by poly ADP ribose polymerase (PARP) cleavage, Bax
      expression, Annexin V-FITC staining, and by the use of antisense oligonucleotides
      against WT1. In summary, our results show that the wt1 gene is a novel target for
      IGF-I action in neurally derived cells.

PMID- 16911582
TI  - The activation loop phosphorylation of protein kinase D is an early marker of
      neuronal DNA damage.
AB  - In neurons, DNA damage induces protein synthesis-dependent apoptosis mediated by
      the mitochondrial intrinsic cell-death pathway. Signal transduction cascades
      activated by genotoxic stress upstream of the mitochondria are largely unknown.
      We identified protein kinase D (PKD) as one of the earliest markers of neuronal
      DNA damage. Phosphorylation of the PKD-activation domain could be detected within
      15 min of genotoxic stress and was concurrent with ataxia telangiectasia-mutated
      (ATM) activation. PKD stimulation was selective to DNA damage and did not occur
      with other stress stimuli examined. In vivo, both young and adult rats showed
      increased levels of phosphorylated PKD in neuronal tissues after injection of DNA
      toxin etoposide. These results indicate that PKD activation is an early neuronal
      response to DNA damage, suggesting that signaling downstream of PKD may be
      critical for neuronal survival after genotoxic stress.

PMID- 16911583
TI  - Cyclin-dependent kinase 5 influences Rohon-Beard neuron survival in zebrafish.
AB  - Cyclin-dependent kinase 5 (cdk5), a member of the cyclin-dependent kinase family,
      is expressed predominantly in post-mitotic cell populations. Unlike the other
      cdks, cdk5 is abundant and most active in differentiated neurons. Here, we
      describe the function of a cdk5 ortholog in zebrafish. Cdk5 catalytic activity is
      meager but present in early stages of development. However, at 24 h post
      fertilization (hpf), the activity is remarkably higher and continues to be high
      through 48 and 72 hpf. Knocking down cdk5 by micro-injection of a specific siRNA
      resulted in decreased cdk5 protein level accompanied by reduced kinase activity.
      In the cdk5 siRNA-injected embryos, the number of primary sensory Rohon-Beard
      (RB) neurons was significantly reduced and there were more apoptotic cells in the
      brain. These phenotypes were rescued by co-injection of cdk5 mRNA. Within the
      first two days of development, RB neurons undergo apoptosis in zebrafish. To
      examine whether cdk5 has a role in RB neuron survival, cdk5 mRNA was injected
      into the one- to two-cell embryos. In these embryos, RB neuron apoptosis was
      inhibited compared with the uninjected control embryos. These results suggest
      that in zebrafish, cdk5 influences RB neuron survival and potentially regulates
      early neuronal development.

PMID- 16911584
TI  - Gene-linked shift in ganglioside distribution influences growth and vascularity
      in a mouse astrocytoma.
AB  - Brain tumor growth and progression is dependent upon vascularity, and is
      associated with altered ganglioside composition and distribution. In this study,
      we examined the influence of gangliosides on growth and vascularity in a
      malignant mouse astrocytoma, CT-2A. Ganglioside distribution was altered in CT-2A
      tumor cells using an antisense construct to beta-1,4-N
      acetylgalactosaminyltransferase (GalNAc-T), a key enzyme that uses the simple
      ganglioside GM3 as a substrate for the synthesis of the more complex
      gangliosides, GM2, GM1 and GD1a. GalNAc-T gene expression was significantly lower
      in CT-2A cells stably transfected with the antisense GalNAc-T plasmid,
      pcDNA3.1/TNG (CT-2A/TNG) than in either non-transfected CT-2A or mock-transfected
      (CT-2A/V) control tumor cells. GM3 was elevated from 16% to 58% of the total
      ganglioside distribution, whereas GM1 and GD1a were reduced from 17% and 49% to
      10% and 17%, respectively, in CT-2A/TNG tumor cells. Growth, vascularity (blood
      vessel density and Matrigel assay) and vascular endothelial growth factor (VEGF)
      expression was significantly less in CT-2A/TNG tumors than in control CT-2A brain
      tumors. In addition, the expression of VEGF, hypoxia-inducible factor 1alpha (HIF
      1alpha) and neuropilin-1 (NP-1) was significantly lower in CT-2A/TNG tumor cells
      than in control CT-2A tumor cells. These data suggest that gene-linked changes in
      ganglioside composition influence the growth and angiogenic properties of the CT
      2A astrocytoma.

PMID- 16911585
TI  - Advanced resources for plant genomics: a BAC library specific for the short arm
      of wheat chromosome 1B.
AB  - Common wheat (Triticum aestivum L., 2n = 6x = 42) is a polyploid species
      possessing one of the largest genomes among the cultivated crops (1C is
      approximately 17 000 Mb). The presence of three homoeologous genomes (A, B and
      D), and the prevalence of repetitive DNA make sequencing the wheat genome a
      daunting task. We have developed a novel 'chromosome arm-based' strategy for
      wheat genome sequencing to simplify this task; this relies on sub-genomic
      libraries of large DNA inserts. In this paper, we used a di-telosomic line of
      wheat to isolate six million copies of the short arm of chromosome 1B (1BS) by
      flow sorting. Chromosomal DNA was partially digested with HindIII and used to
      construct an arm-specific BAC library. The library consists of 65 280 clones with
      an average insert size of 82 kb. Almost half of the library (45%) has inserts
      larger than 100 kb, while 18% of the inserts range in size between 75 and 100 kb,
      and 37% are shorter than 75 kb. We estimated the chromosome arm coverage to be
      14.5-fold, giving a 99.9% probability of identifying a clone corresponding to any
      sequence on the short arm of 1B. Each chromosome arm in wheat can be flow sorted
      from an appropriate cytogenetic stock, and we envisage that the availability of
      chromosome arm-specific BAC resources in wheat will greatly facilitate the
      development of ready-to-sequence physical maps and map-based gene cloning.

PMID- 16911586
TI  - Remote control of photosynthetic genes by the mitochondrial respiratory chain.
AB  - In this paper, we study whether mitochondrial respiration has an impact on the
      biogenesis of photosynthetic apparatus in the unicellular alga, Chlamydomonas
      reinhardtii. When respiration was activated by acetate in the dark, mRNAs of
      nuclear-encoded photosynthetic genes were induced. This induction did not occur
      in the cells treated with respiration inhibitors or in respiration mutants. An
      uncoupler of oxidative phosphorylation did not inhibit this mRNA induction;
      rather, it enhanced it in response to the increase in respiratory electron
      transport (RET). Plant and algal mitochondria have two RET pathways: the
      cytochrome pathway and the alternative pathway. Inhibitors of the former pathway
      inhibited mRNA induction, but inhibitors of the latter enhanced it. Taken
      together, these indicate that photosynthetic gene mRNAs are induced in response
      to activation of the cytochrome pathway. This RET-responsive induction is
      analogous to the photosynthetic electron transport (PET)-responsive induction of
      photosynthetic gene mRNAs (Matsuo and Obokata, Plant Cell Physiol. 43, 1189). PET
      responsive induction occurred in photo-autotrophic and mixotrophic conditions,
      while RET-responsive induction occurred in mixotrophic and dark heterotrophic
      conditions. These results indicate that the regulatory system of photosynthetic
      genes changes between chloroplastic PET-dependent type and mitochondrial RET
      dependent type in response to shifts in the dominant energy source between
      photosynthesis and respiration.

PMID- 16911588
TI  - Analysis of a simulated sprint competition in classical cross country skiing.
AB  - The objectives of this project were first to analyze the physiological response
      of a classical cross country (XC) skiing sprint competition, second, to examine
      the relationships of kinematic and physiological variables with sprint
      performance and third, to test the hypothesis that maximal speed in double poling
      (DP) and diagonal stride (DIAG) predicts sprint performance. Twelve elite skiers
      performed a treadmill-based simulation of a sprint competition that included two
      maximal speed tests (DP, DIAG), a test and three sprint heats over a 3.5-h
      period. VO(2), lactate, heart rate (HR) and kinematic variables were measured.
      Maximal DP and DIAG speed, the level of repeatedly produced lactate values and
      skiing technical aspects positively correlated with sprint performance. Fastest
      skiers produced longer cycle lengths in all techniques at equal poling frequency.
      VO(2) variables showed no correlation to sprint performance. VO(2), tidal volume
      (VT), and lactate decreased over the heats. XC-sprint performance in classical
      style depends on speed abilities, technique use, fatigue resistance, and
      anaerobic capacity. The relationship of maximal speed with sprint performance
      suggests (a) integrating maximal speed tests in XC sprint diagnostics and (b)
      emphasizing training models for XC skiing-specific speed abilities to improve
      performance in XC skiing sprint.

PMID- 16911589
TI  - Is there an association between physical exercise and the quality of life of
      hypertensive patients?
AB  - CONTEXT: Quality of life of hypertensive patients (QOLHP) is associated with
      factors that are not always taken into account in the recommendations made by
      doctors. OBJECTIVE: To evaluate the association between QOLHP and physical
      exercise in an effectiveness approach, i.e. under the actual conditions of
      application of these treatments. METHODOLOGY: In a sample of 361 hypertensive
      patients registered in a primary care center in Tenerife, Spain, the QOLHP is
      measured using the PECVEC questionnaire. The main factor considered is physical
      exercise. In addition, we compiled a set of control variables: pharmacological
      and dietetic treatments, pathological, clinical, functional, psychological,
      social, lifestyle and demographic characteristic of the patients. We explored the
      association between all these factors and the QOLHP by adjusting multiple linear
      regression models. RESULTS: The PECVEC results were between 2.0 and 3.5, with an
      overall Cronbach's alpha reliability statistic of 0.88. From the sample, 58% of
      the patients engage in physical exercise, 75% maintain a anti-hypertension diet
      and 89% take hypertension medication. From all the treatments evaluated, only
      physical exercise is associated directly with all PECVEC scales, especially for
      women and patients over 65. CONCLUSIONS: Recommending the practice of physical
      exercise may be a useful tool for doctors to improve the QOLHP.

PMID- 16911590
TI  - Human cytomegalovirus DNA polymerase catalytic subunit pUL54 possesses
      independently acting nuclear localization and ppUL44 binding motifs.
AB  - The catalytic subunit of human cytomegalovirus (HCMV) DNA polymerase pUL54 is a
      1242-amino-acid protein, whose function, stimulated by the processivity factor,
      phosphoprotein UL44 (ppUL44), is essential for viral replication. The C-terminal
      residues (amino acids 1220-1242) of pUL54 have been reported to be sufficient for
      ppUL44 binding in vitro. Although believed to be important for functioning in the
      nuclei of infected cells, no data are available on either the interaction of
      pUL54 with ppUL44 in living mammalian cells or the mechanism of pUL54 nuclear
      transport and its relationship with that of ppUL44. The present study examines
      for the first time the nuclear import pathway of pUL54 and its interaction with
      ppUL44 using dual color, quantitative confocal laser scanning microscopy on live
      transfected cells and quantitative gel mobility shift assays. We showed that of
      two nuclear localization signals (NLSs) located at amino acids 1153-1159 (NLSA)
      and 1222-1227 (NLSB), NLSA is sufficient to confer nuclear localization on green
      fluorescent protein (GFP) by mediating interaction with importin alpha/beta. We
      also showed that pUL54 residues 1213-1242 are sufficient to confer ppUL44 binding
      abilities on GFP and that pUL54 and ppUL44 can be transported to the nucleus as a
      complex. Our work thus identified distinct sites within the HCMV DNA polymerase,
      which represent potential therapeutic targets and establishes the molecular basis
      of UL54 nuclear import.

PMID- 16911591
TI  - Antagonistic forces generated by cytoplasmic dynein and myosin-II during growth
      cone turning and axonal retraction.
AB  - Cytoplasmic dynein transports short microtubules down the axon in part by pushing
      against the actin cytoskeleton. Recent studies have suggested that comparable
      dynein-driven forces may impinge upon the longer microtubules within the axon.
      Here, we examined a potential role for these forces on axonal retraction and
      growth cone turning in neurons partially depleted of dynein heavy chain (DHC) by
      small interfering RNA. While DHC-depleted axons grew at normal rates, they
      retracted far more robustly in response to donors of nitric oxide than control
      axons, and their growth cones failed to efficiently turn in response to substrate
      borders. Live cell imaging of dynamic microtubule tips showed that microtubules
      in DHC-depleted growth cones were largely confined to the central zone, with very
      few extending into filopodia. Even under conditions of suppressed microtubule
      dynamics, DHC depletion impaired the capacity of microtubules to advance into the
      peripheral zone of the growth cone, indicating a direct role for dynein-driven
      forces on the distribution of the microtubules. These effects were all reversed
      by inhibition of myosin-II forces, which are known to underlie the retrograde
      flow of actin in the growth cone and the contractility of the cortical actin
      during axonal retraction. Our results are consistent with a model whereby dynein
      driven forces enable microtubules to overcome myosin-II-driven forces, both in
      the axonal shaft and within the growth cone. These dynein-driven forces oppose
      the tendency of the axon to retract and permit microtubules to advance into the
      peripheral zone of the growth cone so that they can invade filopodia.

PMID- 16911592
TI  - The global burden of female pelvic floor disorders.

PMID- 16911594
TI  - Advancing the understanding of pathophysiological rationale for the treatment of
      stress urinary incontinence in women: the 'trampoline theory'.

PMID- 16911596
TI  - The treatment of female bladder outlet obstruction.

PMID- 16911598
TI  - Urethral injections for female stress incontinence.
AB  - Emphasis on minimally invasive options for the surgical treatment of stress
      urinary incontinence (SUI) has resulted in the development of agents and
      techniques that improve these conditions substantially towards social continence,
      but currently give suboptimal cure/dry rates. The application of injectable
      therapy as an office procedure implies the potential for cost-efficient treatment
      for selected patients with UI. Continuous advances in materials technology have
      provided the possibility that many new urethral bulking agents will soon be
      available. Experience continues to accrue in clinical trials for urethral bulking
      with these agents, while parallel use for the indication of paediatric vesico
      urethral reflux has also provided evidence of biological activity related to
      these compounds. The agents that are closest to complete analysis are synthetic
      and represent various material types and characteristics. As these materials
      develop, understanding of the preferred injection technique also is being gained.
      The delivery method and site might prove to substantially alter the biological
      activity of these compounds.

PMID- 16911600
TI  - Advances in female stress urinary incontinence: mid-urethral slings.

PMID- 16911602
TI  - Electrical neuromodulatory therapy in female voiding dysfunction.
AB  - Female voiding dysfunction such as urge-frequency syndrome, urge incontinence and
      unobstructive urinary retention are often refractory to conservative management.
      Electrical neuromodulation with surface electrodes or with implantable systems
      has become a valuable addition to the therapeutic options in the last two
      decades. Interstitial cystitis is an emerging indication. The application of
      these techniques in non-neurogenic patients is reviewed. The techniques using
      unimplantable electrodes, anogenital electrical stimulation with plug electrodes,
      transcutaneous electrical nerve stimulation with surface electrodes, and
      posterior tibial nerve stimulation using needle electrodes are addressed. Several
      techniques using implantable systems are discussed, e.g. sacral nerve
      neuromodulation (Interstim device), pudendal nerve stimulation (Interstim and
      Bion device) and paraurethral neuromodulation (Miniaturo device). The long-term
      efficacy of neuromodulation for the established indications is more than half,
      but 20-50% of the patients initially tested do not respond to a test procedure.
      The disadvantage is the high surgical revision rate and the high cost of
      treatment. Technical advances will hopefully be able to address these aspects.

PMID- 16911604
TI  - Neuromodulatory therapies in female pelvic medicine and reconstructive surgery:
      biological agents.
AB  - In recent years, important improvements in the management of patients with
      neurogenic or non-neurogenic detrusor overactivity and urge incontinence have
      been brought about by the introduction of vanilloids and botulinum toxins in
      urology. In this review we introduce the new therapeutic options, provides basic
      information, and summarize the results experienced so far.

PMID- 16911606
TI  - Robotic and laparoscopic female pelvic floor reconstruction.

PMID- 16911608
TI  - The use of synthetic mesh in female pelvic reconstructive surgery.

PMID- 16911610
TI  - Developments in pharmacological therapy for the overactive bladder.

PMID- 16911612
TI  - Advances in geriatric female pelvic surgery.

PMID- 16911614
TI  - Current diagnosis and treatment algorithms for anal incontinence.

PMID- 16911616
TI  - Open and unresolved clinical questions in female pelvic medicine and
      reconstructive surgery.

PMID- 16911617
TI  - The social and economic consequences of childhood-onset Type 1 diabetes mellitus
      across the lifecourse: a systematic review.
AB  - BACKGROUND: The incidence of childhood-onset (Type 1) diabetes is high, and
      increasing, particularly among the very young. The aim of this review was to
      determine the longer-term social consequences of having diabetes as a child and
      to determine whether adverse consequences are more severe for disadvantaged
      children. METHODS: Results from published and unpublished studies were
      synthesized narratively to examine the impact of diabetes on education,
      employment and income in adulthood. The question of whether the impact differed
      for different social groups was also examined. RESULTS: Case-control studies
      found that children with diabetes missed more school than healthy children. Most
      studies of attainment found no differences between children with diabetes and non
      diabetic control subjects or the local population, although poor metabolic
      control, early-onset, longer illness duration and serious hypoglycaemic events
      were associated with underachievement. People with childhood-onset diabetes may
      experience disadvantage in employment, and have a lower income in adulthood,
      although diabetic complications appear to be the most important determinant of
      social consequences in later life. CONCLUSIONS: Many children with diabetes-
      especially late-onset--perform equally well at school despite increased rates of
      absence, but it is not yet clear whether specific subgroups are at greater risk
      of educational underperformance. People with childhood-onset diabetes, however,
      do appear to experience some disadvantage in adult employment. Qualitative
      research and cohort studies are needed to fill key gaps in the existing evidence
      base. Future research must also examine the impact of diabetes-related risk
      factors on socio-economic consequences.

PMID- 16911618
TI  - Social consumption of alcohol in adolescents with Type 1 diabetes is associated
      with increased glucose lability, but not hypoglycaemia.
AB  - AIM: To determine the effects of social consumption of alcohol by diabetic
      adolescents on glycaemic control. METHODS: Fourteen (five male) patients aged >
      16 years were recruited from the diabetes clinic at the Royal Children's
      Hospital. The continuous glucose monitoring system (CGMS) was attached at a
      weekend when alcohol consumption was planned for one night only. For each
      patient, the 12-h period from 18.00 h to 06.00 h for the night with alcohol
      consumption (study period) was compared with the same period with non-alcohol
      consumption (control period) either 24 h before or after the alcohol study night.
      Thus, each subject was his/her own control. Glycaemic outcomes calculated from
      continuous glucose monitoring included mean blood glucose (MBG), percentage of
      time spent at low glucose levels (CGMS < 4.0 mmol/l), normal glucose levels (CGMS
      4.0-10.0 mmol/l) and high glucose levels (> 10.0 mmol/l) and continuous overall
      net glycaemic action (CONGA). RESULTS: The mean number of standard alcohol drinks
      consumed during the study period was 9.0 for males and 6.3 for females. There was
      no difference in percentage of time at high and normal glucose levels in the
      study and control periods. During the control period, there was a higher
      percentage of time with low glucose levels compared with the study period (P <
      0.05). There was an increased level of glycaemic variation during the study time
      when compared with the control period. CONCLUSIONS: In an uncontrolled, social
      context, moderately heavy alcohol consumption by adolescents with Type 1 diabetes
      appears to be associated with increased glycaemic variation, but not with low
      glucose levels.

PMID- 16911619
TI  - GAD antibodies in probands and their relatives in a cohort clinically selected
      for Type 2 diabetes.
AB  - AIMS: A subset of patients who present as if they have Type 2 diabetes have
      positive pancreatic autoantibodies, and have been referred to as having latent
      autoimmune diabetes in adults (LADA). We assessed the prevalence and clinical
      characteristics of patients with glutamic acid decarboxylase antibodies (GADA) in
      a cohort clinically selected for Type 2 diabetes and determined the presence of
      diabetes and GADA in their first-degree relatives. METHODS: GADA were measured in
      2059 subjects, not known to be related, and clinically selected as having Type 2
      diabetes for genetic studies. Clinical characteristics were compared in GADA
      positive and GADA negative subjects. Diabetes and GAD antibody status were
      compared in 208 first-degree relatives of GADA positive and GADA negative
      probands. RESULTS: Of the subjects, 136 (7%) were GADA positive. Compared with
      the GADA negative subjects, they were slimmer (P < 0.001), diagnosed at a younger
      age (P = 0.011) and progressed to insulin faster (P < 0.001). Thirty-three per
      cent of GADA positive subjects had a first-degree relative with diabetes compared
      with 42% of GADA negative subjects (P = 0.034). The overall prevalence of GADA
      was similar in the first-degree relatives of GADA positive and GADA negative
      probands (4 v 5%), and 19 of 22 (86%) diabetic relatives of GADA positive
      probands were GADA negative. CONCLUSION: Despite clinically selecting a Type 2
      diabetes cohort, 7% were GADA positive with an altered phenotype. These GADA
      positive patients had a strong family history of non-autoimmune diabetes. This
      suggests that, in this subgroup of patients, autoimmune pancreatic beta-cell
      destruction occurs on a background of Type 2 diabetes genetic susceptibility.

PMID- 16911620
TI  - Prevalence and associations of low plasma erythropoietin in patients with Type 2
      diabetes mellitus.
AB  - AIMS: Low plasma erythropoietin (EPO) is a key causal factor in the anaemia of
      diabetic patients. The aim of this study was to investigate the prevalence of
      anaemia in relation to EPO in patients with Type 2 diabetes. METHODS: In a clinic
      based cross-sectional study of 161 Type 2 diabetes patients, we measured EPO,
      ferritin and full blood count. The patients were classified on the basis of the
      urine albumin:creatinine excretion ratio as normo-, micro- or macroalbuminuric.
      Serum creatinine, cystatin C and glomerular filtration rate (GFR) calculated from
      cystatin C were used as markers of renal function. All the patients were assessed
      for symptoms and signs of diabetic complications, including diabetic peripheral
      sensory neuropathy (PSN). RESULTS: Twenty-one (13.0%) patients were anaemic; 80
      patients (49.7%) had low EPO (< 5 mU/ml), of whom 28.8% had a GFR < 60 ml/min per
      1.73 m2; 57.5% were normoalbuminuric, 33.7% were microalbuminuric and 8.8%
      macroalbuminuric. Although EPO was significantly higher in anaemic patients
      compared with non-anaemic patients, the EPO response was inappropriate for the
      degree of anaemia. Of patients with PSN, 66.7% had low EPO but there was no
      significant difference in EPO between patients with and without PSN. Log EPO
      correlated significantly with urine microalbumin:creatinine ratio and logistic
      regression analysis showed that haemoglobin, age and urine microalbumin:
      creatinine ratio were the main determinants of EPO. CONCLUSIONS: The degree of
      microalbuminuria is the most significant determinant of plasma EPO, which is
      often low or inappropriately normal in diabetic patients with and without
      anaemia.

PMID- 16911621
TI  - Intimal media thickness, glucose intolerance and metabolic syndrome in Asian
      Indians--the Chennai Urban Rural Epidemiology Study (CURES -22).
AB  - AIMS: The aim of the present study was to assess carotid intimal media thickness
      (IMT) in different grades of glucose intolerance and the metabolic syndrome (MS)
      in Asian Indians, a high-risk group for diabetes and coronary artery disease.
      METHODS: Subjects with normal glucose tolerance (NGT) (n = 1600), impaired
      glucose tolerance (IGT) (n = 330), newly diagnosed diabetes (NDD) (n = 330) and
      known diabetes (KD) (n = 1170) were recruited from the Chennai Urban Rural
      Epidemiology Study (CURES), an ongoing study on a representative population of
      Chennai (formerly Madras), in southern India. Assessment of carotid IMT was
      performed using high-resolution B-mode ultrasonography. MS was defined using
      modified adult treatment parel (ATP) III guidelines. Subjects with self-reported
      diabetes, hypertension and dyslipidaemia were excluded from the analysis on MS.
      RESULTS: Subjects with glucose intolerance had significantly higher mean carotid
      IMT values compared with subjects with normal glucose tolerance (NGT 0.69 +/-
      0.12 mm, IGT 0.75 +/- 0.16 mm, NDD 0.79 +/- 0.19 mm and KD 0.87 +/- 0.24 mm, P <
      0.001). Regression analysis showed that there was a linear increase in mean IMT
      values with increasing severity of glucose intolerance, even after adjusting for
      age and gender. Mean IMT values were higher in those with MS and increased with
      increase in number of metabolic abnormalities (subjects without any metabolic
      abnormality 0.66 +/- 0.12 mm, one abnormality 0.67 +/- 0.13 mm, two 0.70 +/- 0.12
      mm, three 0.72 +/- 0.12 mm, four 0.77 +/- 0.15 mm, five 0.76 +/- 0.13 mm).
      Regression models showed MS to be associated with IMT, even after adjusting for
      age, gender and presence of diabetes (P = 0.021). CONCLUSIONS: In Asian Indians,
      carotid IMT increases progressively with increasing severity of glucose
      intolerance and is also associated with the metabolic syndrome, independent of
      age, gender and presence of diabetes.

PMID- 16911622
TI  - Quality of care in diabetic patients attending routine primary care clinics
      compared with those attending GP specialist clinics.
AB  - AIM: To determine the impact on clinical outcomes of specialist diabetes clinics
      compared with routine primary care clinics. METHODS: Observational study
      measuring clinical performance (process/outcome measures) in the primary care
      sector. A cohort of patients attending specialist diabetes clinics was compared
      with a control cohort of patients attending routine primary care clinics.
      RESULTS: Patients seen in specialist diabetes clinics had a significantly higher
      HbA1c than patients in routine primary care clinics (mean difference 0.58%; P <
      0.001) but there was no significant difference in rate of improvement with visits
      compared with primary care clinics. In contrast, patients seen in the routine
      primary care clinics had significantly higher cholesterol levels (mean difference
      0.24 mmol/l; P < 0.001) compared with patients in specialist diabetes clinics and
      their improvement was significantly greater over time (mean difference 0.14
      mmol/l per visit compared with 0.10 mmol/l; P < 0.006). Patients in routine
      primary care clinics also had significantly higher diastolic blood pressure (mean
      difference 1.6 mmHg; P < 0.007) but there was no difference in improvement with
      time compared with specialist diabetes clinics. Uptake of podiatry and retinal
      screening was significantly lower in patients attending routine primary care
      clinics, but this difference disappeared with time, with significant increases in
      uptake in the primary care clinic group. Weight increased in both groups
      significantly with time, but more so in the specialist clinic patients (mean
      increase 0.18 kg per visit more compared with routine clinic primary care
      patients; P < 0.001). CONCLUSIONS: This study provides evidence that the
      provision of primary care services for patients with diabetes, whether
      traditional general practitioner clinics or diabetes clinics run by general
      practitioners with special interests, is effective in reducing HbA1c, cholesterol
      and blood pressure. However, the same provision of care was unable to prevent
      increasing weight or creatinine over time. No evidence was found that patients in
      specialist clinics do better than patients in routine primary care clinics.

PMID- 16911623
TI  - Incidence and trends of childhood Type 1 diabetes worldwide 1990-1999.
AB  - AIM: To examine incidence and trends of Type 1 diabetes worldwide for the period
      1990-1999. METHODS: The incidence of Type 1 diabetes (per 100 000/year) was
      analysed in children aged <or= 14 years from 114 populations in 112 centres in 57
      countries. Trends in the incidence of Type 1 diabetes were analysed by fitting
      Poisson regression models to the dataset. RESULTS: A total of 43,013 cases were
      diagnosed in the study populations of 84 million children. The age-adjusted
      incidence of Type 1 diabetes among 112 centres (114 populations) varied from 0.1
      per 100,000/year in China and Venezuela to 40.9 per 100,000/year in Finland. The
      average annual increase in incidence calculated from 103 centres was 2.8% (95% CI
      2.4-3.2%). During the years 1990-1994, this increase was 2.4% (95% CI 1.3-3.4%)
      and during the second study period of 1995-1999 it was slightly higher at 3.4%
      (95% CI 2.7-4.3%). The trends estimated for continents showed statistically
      significant increases all over the world (4.0% in Asia, 3.2% in Europe and 5.3%
      in North America), except in Central America and the West Indies where the trend
      was a decrease of 3.6%. Only among the European populations did the trend in
      incidence diminish with age. CONCLUSIONS: The rising incidence of Type 1 diabetes
      globally suggests the need for continuous monitoring of incidence by using
      standardized methods in order to plan or assess prevention strategies.

PMID- 16911624
TI  - Comparative study of the polaroid and digital non-mydriatic cameras in the
      detection of referrable diabetic retinopathy in Australia.
AB  - AIM: To show that the non-mydriatic retinal camera (NMRC) using polaroid film is
      as effective as the NMRC using digital imaging in detecting referrable
      retinopathy. METHODS: A series of patients with diabetes attending the eye out
      patients department at the Royal Victorian Eye and Ear Hospital had single-field
      non-mydriatic fundus photographs taken using first a digital and then a polaroid
      camera. Dilated 30 degrees seven-field stereo fundus photographs were then taken
      of each eye as the gold standard. The photographs were graded in a masked
      fashion. Retinopathy levels were defined using the simplified Wisconsin Grading
      system. We used the kappa statistics for inter-reader and intrareader agreement
      and the generalized linear model to derive the odds ratio. RESULTS: There were
      196 participants giving 325 undilated retinal photographs. Of these participants
      111 (57%) were males. The mean age of the patients was 68.8 years. There were 298
      eyes with all three sets of photographs from 154 patients. The digital NMRC had a
      sensitivity of 86.2%[95% confidence interval (CI) 65.8, 95.3], whilst the
      polaroid NMRC had a sensitivity of 84.1% (95% CI 65.5, 93.7). The specificities
      of the two cameras were identical at 71.2% (95% CI 58.8, 81.1). There was no
      difference in the ability of the polaroid and digital camera to detect referrable
      retinopathy (odds ratio 1.06, 95% CI 0.80, 1.40, P = 0.68). CONCLUSION: This
      study suggests that non-mydriatic retinal photography using polaroid film is as
      effective as digital imaging in the detection of referrable retinopathy in
      countries such as the USA and Australia or others that use the same criterion for
      referral.

PMID- 16911625
TI  - The role of endothelial dysfunction in the pathophysiology of erectile
      dysfunction in diabetes and in determining response to treatment.
AB  - BACKGROUND: Erectile dysfunction (ED) in diabetes is related to autonomic
      neuropathy and endothelial dysfunction. We studied the relative importance of
      these factors in diabetic and non-diabetic men with ED and determined if they
      predict responses to treatment with sildenafil. METHODS: Thirty-three men, aged
      35-65 years, with ED (20 diabetic, 13 non-diabetic), 15 of whom were sildenafil
      responders and 18 non-responders, were compared with 30 age and risk-matched
      control subjects (15 diabetic, 15 non-diabetic). Subjects with ED completed the
      International Index of Erectile Function (IIEF) questionnaire. Endothelial
      function was assessed by changes in brachio-radial and femoro-tibial arterial
      pulse-wave velocity (pulse-wave velocity) during reactive hyperaemia, expressed
      as percentage endothelium-dependent dilatation. Autonomic function was assessed
      by heart rate variation during expiration and inspiration (E/I ratio) and during
      the valsalva manoeuvre. RESULTS: The respective changes in pulse-wave velocity,
      in the arm and leg [mean (sd)] were 0.71 (6.5)% and 3.5 (6.4)% in the impotent
      diabetic men, 0.7 (7.6)% and 2.4 (5.9)% in the non-diabetic impotent men, -0.68
      (5.7)% and -1.31 (7.2)% in the non-impotent diabetic men and 7.7 (3.7)% and 7.6
      (3.4)% in the control subjects. There was a significant interaction between ED
      and diabetic status such that there was significantly impaired vascular response
      in the diabetic group (both with and without ED) and in the non-diabetic group
      with ED compared with the non-diabetic control group (P = 0.01 and P = 0.001 for
      brachio-radial and femoro-tibial measures, respectively). The E/I ratios of the
      diabetic men were significantly lower than those of the control subjects [1.17
      (0.14) vs. 1.33 (0.16), P < 0.02), but there were no differences in the measures
      of autonomic neuropathy between the groups with ED and those with normal erectile
      function. Amongst diabetic men, the initial IIEF scores (maximum score 30, low
      score indicates more severe ED) were significantly higher in sildenafil
      responders than non-responders [16.3 (8.4), vs. 6.8 (7 1), P < 0.02]. The rate of
      sildenafil response was not significantly affected by the measures of endothelial
      or autonomic function. CONCLUSIONS: ED in both diabetic and non-diabetic men is
      characterized by marked endothelial dysfunction in comparison with non-diabetic
      control subjects. Response to sildenafil is not predicted by either endothelial
      function or autonomic function, but in diabetic men appears to be related to the
      initial degree of erectile dysfunction.

PMID- 16911627
TI  - Relationship of glucose concentrations with PAI-1 and t-PA in subjects with
      normal glucose tolerance.
AB  - AIM: To study metabolic risk factors for the development of cardiovascular
      disease (CVD), including markers of the fibrinolytic system in relation to blood
      glucose levels in subjects with normal glucose tolerance and fasting blood
      glucose levels below 5.6 mmol/l. METHODS: Cross-sectional, community-based study
      from a primary health-care centre of adult subjects with normal glucose
      tolerance. Analysis of fasting and 2-h post-load blood glucose concentrations
      were centralized and related to anthropometric characteristics, metabolic
      variables, inflammatory markers, and coagulation and fibrinolytic variables.
      RESULTS: Increasing fasting blood glucose concentrations within the normal range
      in subjects with normal glucose tolerance were associated with increasing age,
      body mass index, and waist circumference, and with increasing concentrations of
      metabolic risk factors for development of CVD. After adjustment for gender, age,
      body mass index (BMI), and fasting insulin, levels of plasmin activator inhibitor
      (PAI-1) and tissue type plasminogen activator (t-PA) increased significantly with
      increasing levels of fasting glucose within the normal range (P = 0.012 and P <
      0.0001, respectively). CONCLUSIONS: We found risk factors for CVD, specifically
      key components of the fibrinolytic system, PAI-1 and t-PA, increased with
      increasing fasting glucose levels even in subjects with normal glucose tolerance.
      This observation may help to explain the increased risk of CVD with increasing
      values of fasting glucose in the normal range.

PMID- 16911626
TI  - Twice-daily compared with once-daily insulin glargine in people with Type 1
      diabetes using meal-time insulin aspart.
AB  - AIM: To compare blood glucose control when using insulin glargine twice daily at
      breakfast- and dinner-times with insulin glargine once daily at dinner time, in
      unselected people with Type 1 diabetes using insulin aspart at meal-times.
      METHODS: In this 8-week, two-way, cross-over study, 20 people with Type 1
      diabetes were randomized to insulin glargine injection once daily at dinner-time
      or twice daily at breakfast- and dinner-times, both plus meal-time insulin
      aspart. Each 4-week treatment period concluded with a 24-h inpatient metabolic
      profile. RESULTS: Insulin doses, HbA1c, fructosamine concentration and pre
      breakfast self-monitored blood glucose (SMBG) concentration did not differ
      between treatment periods. SMBG concentrations after breakfast, after lunch and
      before dinner were lower with twice-daily compared with once-daily dinner-time
      glargine [9.3 +/- 0.5 (+/- se) vs. 6.7 +/- 0.5 mmol/l, P = 0.003; 10.2 +/- 0.9
      vs. 7.0 +/- 0.9 mmol/l, P = 0.024; 9.6 +/- 0.5 vs. 6.6 +/- 0.5 mmol/l, P =
      0.001]. Mean 24-h SMBG concentration was lower with twice-daily glargine (7.1 +/-
      0.5 vs. 8.8 +/- 0.5 mmol/l, P = 0.031). Within-day variability of SMBG
      concentration was lower with twice-daily glargine (sd 3.2 +/- 0.2 vs. 4.0 +/- 0.3
      mmol/l, P = 0.044). Plasma free insulin concentration was higher in the afternoon
      with twice-daily glargine (21.9 +/- 1.4 vs. 16.1 +/- 1.3 mU/l, P = 0.009), but
      lower overnight (12.1 +/- 1.7 vs. 17.8 +/- 1.7 mU/l, P = 0.030), compared with
      once-daily injection. Plasma glucose concentration overnight was higher with
      twice-daily compared with once-daily glargine (mean 9.0 +/- 0.4 vs. 6.6 +/- 0.4
      mmol/l, P = 0.001). CONCLUSIONS: Blood glucose concentration rises in the late
      afternoon in association with falling plasma insulin levels towards the end of
      the 24-h period after insulin glargine injection in some people with Type 1
      diabetes using once-daily glargine at dinner-time plus a rapid-acting insulin
      analogue at meal-times. This is prevented by twice-daily injection of insulin
      glargine.

PMID- 16911629
TI  - Long-term benefits of continuous subcutaneous insulin infusion in children with
      Type 1 diabetes: a 4-year follow-up.
AB  - AIM: To determine the safety and effectiveness of continuous subcutaneous insulin
      infusion (CSII) in attaining long-term glycaemic control in paediatric patients
      with Type 1 diabetes and to compare the results with those previously recorded in
      the same patients taking multiple daily injections (MDI) (four injections a day).
      METHODS: Forty-two patients (mean age 12.2 +/- 3.4 years; range 4.5-17 years; 24
      males; mean duration of Type 1 diabetes 5.1 +/- 3.0 years) were studied. The
      following parameters were assessed in the year before starting CSII treatment
      (during MDI treatment) and during the 4 years of insulin pump treatment: annual
      mean HbA1c, insulin requirements (U/kg per day), annual mean of body mass index
      (BMI) z scores, and adverse events (severe hypoglycaemia and diabetic
      ketoacidosis/patient per year). Two patients discontinued pump therapy (after 1
      year and 2-year follow-up, respectively) because of non-compliance with CSII
      therapy. RESULTS: Compared with the annual mean HbA1c observed prior to CSII
      therapy (8.9 +/- 1.0%), the mean HbA1c levels were lower during the first (8.2 +/
      0.9%; P = 0.00), second (8.6 +/- 1.0%; P = 0.05), third (8.4 +/- 0.9%; P = 0.01)
      and fourth (8.2 +/- 1%; P = 0.00) year of CSII therapy. The insulin requirements
      (U/kg per day) decreased during CSII treatment compared with MDI treatment.
      Compared with the annual mean of BMI z scores prior to CSII therapy, BMI z scores
      were significantly lower during the third and fourth years of CSII therapy.
      Through the first, second, third and fourth years of follow-up the number of
      episodes of severe hypoglycaemia (20.0, 20.0, 20.0 and 0 episodes/1000 patient
      years, respectively) and diabetic ketoacidosis (0.05, 0.00, 0.03 and 0.00
      episodes/patient per year, respectively), events were similar to that in the year
      preceding CSII therapy (20.0 and 0.03, respectively). CONCLUSION: In this
      population of selected patients in our clinic, CSII appears to be a safe and
      effective therapeutic alternative to MDI treatment. This therapy may ensure a
      stable improvement in long-term glycaemic control in paediatric patients, with no
      increase in diabetic ketoacidosis and severe hypoglycaemic events and, on the
      other hand, with a trend of reduction in BMI z scores.

PMID- 16911628
TI  - Aldose reductase gene is associated with diabetic macroangiopathy in Japanese
      Type 2 diabetic patients.
AB  - AIMS: The aldose reductase (AR) gene, a rate-limiting enzyme of the polyol
      pathway, has been investigated as a candidate gene in determining susceptibility
      to diabetic microangiopathy. However, the association of the AR gene with
      diabetic macroangiopathy has not been investigated. Therefore, the present study
      was conducted to determine whether genetic variations of AR may determine
      susceptibility to diabetic macroangiopathy. METHODS: There were 378 Type 2
      diabetic patients enrolled in this study. A single nucleotide polymorphism in the
      promoter region (C-106T) was genotyped and the AR protein content of erythrocytes
      measured by ELISA. RESULTS: There were no significant differences in genotypic or
      allelic distribution in patients with or without ischaemic heart diseases, but
      there was a significant increase in the frequency of the CT + TT genotype and T
      allele in patients with stroke (P = 0.019 and P = 0.012). The erythrocyte AR
      protein content was increased in patients with the CT and TT genotype compared
      with those with the CC genotype. After adjustment for age, duration of diabetes,
      body mass index, systolic blood pressure, HbA1c, and serum creatinine,
      triglycerides, and total cholesterol in multivariate logistic-regression models,
      the association between this AR genotype and stroke remained significant.
      CONCLUSIONS: Our results suggest that the CT or TT genotype of the AR gene might
      be a genetic marker of susceptibility to stroke in Type 2 diabetic patients. This
      observation might contribute to the development of strategies for the prevention
      of stroke in Type 2 diabetic patients.

PMID- 16911630
TI  - Direct association of a promoter polymorphism in the CD36/FAT fatty acid
      transporter gene with Type 2 diabetes mellitus and insulin resistance.
AB  - AIMS: The membrane-bound fatty acid transporter CD36/FAT may play a role in
      disturbed fatty acid handling as observed in the metabolic syndrome and Type 2
      diabetes mellitus (T2DM). Genetic variation in the CD36 gene may contribute to
      the aetiology of diabetes. METHODS: A population-based cohort in the Netherlands
      [age > 40 years and body mass index (BMI) > 25 kg/m2] of 675 subjects was
      phenotyped with respect to glucose metabolism with an oral glucose tolerance test
      and was genotyped for a known 478C-->T substitution and a C/T snp in the upstream
      promoter region (rs1527479) in the CD36 gene. RESULTS: T2DM was more prevalent in
      the TT genotype than in the CC genotype. This was most pronounced in women and in
      subjects with a high BMI (BMI > 27 kg/m2). In addition, within the group of
      diabetic patients, the TT genotype was commoner in subjects with increased
      homeostasis model assessment (HOMA) index for insulin resistance. The 478C-->T
      substitution, previously found in the Japanese population, was not found in our
      caucasian population. CONCLUSIONS: This is the first study to show a direct
      association of a CD36 snp with T2DM. Moreover, within the diabetic subjects, this
      CD36 snp was associated with insulin resistance (HOMA index).

PMID- 16911631
TI  - Searching for diabetes decision aids and related background information.
AB  - AIMS: Patient decision aids (DAs) are interventions designed to help patients
      making informed decisions. DAs are complex interventions comprising a number of
      active components each essential to the proper functioning of the aid. Critical
      appraisal of DAs therefore requires access to information describing the
      incremental assessment of each stage in their development, including information
      about the theoretical funding, development processes, efficacy trials and long
      term implementation. We explored the feasibility of identifying such information
      with conventional database search strategies. Our study was conducted only in the
      field of diabetes care. METHODS: The 'Inventory of Existing Patient Decision
      Aids', medline (PubMed) and the World Wide Web were used to identify DAs relevant
      for diabetes care. For tracking information concerning each developmental stage,
      the reference lists of the DAs, home pages of the authors, medline, embase,
      PsycINFO, cinahl, and the Cochrane database were searched systematically.
      RESULTS: A total of 13 DAs relevant for diabetes care were identified. The search
      for publications concerning their development yielded more than 3000 results,
      only 10 of which referred to at least one of the 13 DAs. No additional background
      information was found on the home pages of the authors. CONCLUSIONS: Conventional
      database search strategies do not allow the extraction of information about the
      stages in development of a DA. To facilitate critical appraisal of DAs, we
      propose the creation of an electronic database which provides information about
      available DAs, together with the relevant background literature, or to
      incorporate such a system into existing databases.

PMID- 16911632
TI  - Do people with diabetes who need to talk want to talk?
AB  - AIM: Our objective was to determine whether people with diabetes who ask for
      psychological support are those who are experiencing clinically significant
      levels of psychological distress. METHOD: Three hundred people with diabetes were
      asked to complete psychometrically validated questionnaires that assessed
      subjective need and objective psychological distress. RESULTS: High levels of
      psychological distress were reported: 25% reported depressive symptomatology, 41%
      reported clinically significant levels of anxiety and 51% reported some binge
      eating behaviour. Participants also indicated a desire to talk to diabetes
      professionals about various problem areas in diabetes. Those reporting
      psychological distress, especially depression, were most likely to indicate a
      desire to talk to someone about living with diabetes. CONCLUSIONS: Those who want
      to talk are those who need to talk. Future service development issues should
      acknowledge the needs and expressed wishes of service users.

PMID- 16911634
TI  - Tolerance loss in diabetics: association with foreign antigen exposure.

PMID- 16911633
TI  - The effects of calcitriol and nicotinamide on residual pancreatic beta-cell
      function in patients with recent-onset Type 1 diabetes (IMDIAB XI).
AB  - BACKGROUND: A number of recent studies underline the importance of vitamin D in
      the pathogenesis of Type 1 diabetes (T1D). AIMS: The aim of this study was to
      investigate whether supplementation with the active form of vitamin D
      (calcitriol) in subjects with recent-onset T1D protects residual pancreatic beta
      cell function and improves glycaemic control (HbA(1c) and insulin requirement).
      METHODS: In this open-label randomized trial, 70 subjects with recent-onset T1D,
      mean age 13.6 years +/- 7.6 sd were randomized to calcitriol (0.25 microg on
      alternate days) or nicotinamide (25 mg/kg daily) and followed up for 1 year.
      Intensive insulin therapy was implemented with three daily injections of regular
      insulin + NPH insulin at bedtime. RESULTS: No significant differences were
      observed between calcitriol and nicotinamide groups in respect of
      baseline/stimulated C-peptide or HbA1c 1 year after diagnosis, but the insulin
      dose at 3 and 6 months was significantly reduced in the calcitriol group.
      CONCLUSIONS: At the dosage used, calcitriol has a modest effect on residual
      pancreatic beta-cell function and only temporarily reduces the insulin dose.

PMID- 16911635
TI  - The functional variant -169C/T in the FCRL3 gene does not increase susceptibility
      to Type 1 diabetes.

PMID- 16911636
TI  - The PAX4 gene variant A1168C is not associated with early onset Type 1 diabetes
      in a UK population.

PMID- 16911639
TI  - Effect of protein C and activated protein C on alveolar fibrin deposition and
      turnover in a piglet model of septic shock.

PMID- 16911640
TI  - Human papillomavirus and head and neck cancer: a systematic review and meta
      analysis.
AB  - It has been suggested that the link between human papillomavirus (HPV) and head
      and neck squamous cell carcinoma (HNSCC) is specific to carcinoma of the tonsil.
      We systematically reviewed studies that tested for HPV16 exposure in anatomically
      defined sites in the head and neck and a control group. The association between
      HPV16 and cancer was strongest for tonsil (OR: 15.1, 95% CI: 6.8-33.7),
      intermediate for oropharynx (OR: 4.3, 95% CI: 2.1-8.9) and weakest for oral (OR:
      2.0, 95% CI: 1.2-3.4) and larynx (OR: 2.0, 95% CI: 1.0-4.2). To investigate
      heterogeneity, further stratification by method of HPV16 detection, suggested
      that variation in the magnitude of the HPV-cancer association with cancer site
      was restricted to studies using ELISA: among studies using PCR, the magnitude of
      the summary odds ratios was similar across the four sites. The association
      between HPV16 infection and HNSCC in specific sites suggests the strongest and
      most consistent association is with tonsil cancer, and the magnitude of this
      association is consistent with an infectious aetiology. However, the method of
      viral detection may be an important source of heterogeneity. Resolution of this
      issue will require further studies using both methods, examining associations
      separately in different sites.

PMID- 16911641
TI  - Botulinum toxin in the management of sialorrhoea: a systematic review.
AB  - Sialorrhoea can be a significant problem in both adults and children and can
      cause both physical and psychosocial problems. Botulinum toxin has enjoyed an
      emergence in the treatment of sialorrhoea, a systematic review of the evidence
      for botulinum toxin reveals two randomised controlled trials (RCTs) and four
      other trials that fulfilled our inclusion criteria. Both RCTs demonstrate the
      effectiveness of botulinum toxin in the management of sialorrhoea. There was no
      clear evidence for one antigenic type of botulinum toxin over another and minimal
      evidence for the optimal dose of botulinum toxin for each antigenic type. No
      advantage is conferred in using ultrasound guidance in injecting the glands. None
      of the RCTs or other studies directly compared submandibular versus parotid
      injection or directly compared botulinum toxin against surgery. Minor side
      effects were reported in one of the RCTs but overall botulinum toxin is a safe,
      minimally invasive and effective means in the treatment of sialorrhoea with the
      potential to become the treatment of choice. Our review demonstrates that further
      randomised controlled trials are required to more fully evaluate this new
      modality of treatment.

PMID- 16911642
TI  - Patient's quality of life and hearing outcomes after stapes surgery.
AB  - OBJECTIVES: To determine the quality of life (QOL) after stapes surgery and
      whether audiological parameters for hearing correlate with specific QOL factors.
      DESIGN: A retrospective cross-sectional study. SETTING: A tertiary referral
      centre. PARTICIPANTS: A series of 35 patients who underwent stapes surgery of
      which three were excluded because they were <18 years of age, chronically or
      mentally ill, or in a dependant relationship. Response rate was 93% (30/32). Nine
      were further excluded because they had revision or bilateral surgery, or missing
      data. Twenty-one patients were included in this study. MAIN OUTCOME MEASURES: The
      Glasgow Benefit Inventory (GBI) was used to evaluate general QOL and the Hearing
      Disability and Handicap Scale (HDHS) was used as a disease-specific measure. The
      Belfast Rule of Thumb and Glasgow Benefit Plot assessed hearing outcomes.
      RESULTS: Operative success was 86% using the Belfast Rule of Thumb and 95% had
      closure of the air-bone gap to within 20 dB. 81.8% of patients reported a better
      overall QOL as surgery. Glasgow Benefit Inventory Social and GBI Physical scores
      correlated positively with the HDHS speech component (P < 0.05). The duration of
      hearing loss correlated inversely with the average HDHS score (P < 0.05).
      CONCLUSION: The majority of patients report a better QOL as undergoing stapes
      surgery. Speech impacts on people's physical and social QOL of patients. Quality
      of life tools, in addition to objective audiologic measurements can provide
      clinicians with patients' subjective perspective that helps guide clinical
      decision-making and counselling.

PMID- 16911643
TI  - Cochlear implantation in obstructed cochleas: the effect of the degree of
      obstruction on the number of activated electrodes and the amount of postoperative
      speech perception.
AB  - OBJECTIVE: With cochlear implantation, insertion of the electrodes can be
      hampered by cochlear obstructions. The aim of this study was to investigate the
      effects of these obstructions on the number of activated electrodes and
      postoperative speech perception. STUDY DESIGN AND SETTING: Retrospective analysis
      of the operation reports and CT-scans of patients who underwent cochlear
      implantation, at the Department of Otorhinolaryngology of the University Medical
      Center of Utrecht (n = 295). PATIENTS AND INTERVENTIONS: Fifty patients with a
      certain degree of cochlear obstruction were included. Based on the surgical
      intervention to overcome these obstructions they were subdivided into first-,
      second- and third degree obstructions. The number of implanted and activated
      electrodes was determined. MAIN OUTCOME MEASURES: Three different speech
      perception tests after 12 months of cochlear implant use. RESULTS: The number of
      activated electrodes significantly diminished with increasing obstruction degree
      (P < 0.01). This was caused by a lower amount of implanted electrodes combined
      with a higher amount of switched off electrodes. With a higher degree of
      obstruction the amount of postoperative speech perception decreased significantly
      (P < 0.01). This is partly explained by the lower number of activated electrodes
      and partly explained by the fact that a higher obstructions degree correlates
      with a higher degree of (retro-) cochlear pathology. Significantly more
      electrodes can be inserted into the severely obstructed cochlea using a Double
      Array Cochlear Implant. CONCLUSION: Cochlear obstructions pose a surgical threat
      and negatively influence the postoperative speech perception results.
      Fortunately, due to surgical techniques, first and second degree obstructed
      cochleas can often be bypassed. Implanting of a Double Array implant brightens
      the prospects of patients with third (severe) degree obstructed cochleas.

PMID- 16911644
TI  - A comparison of temporal bone fracture classification systems.
AB  - OBJECTIVES: To compare the traditional and otic capsule classification system of
      temporal bone fractures for clinical relevance. DESIGN: A retrospective review of
      all patients with a radiological diagnosis of a skull-base fracture over a 5-year
      period. SETTING: All patients were seen at Beaumont Hospital, the national
      tertiary referral centre for Neuro-otology. PARTICIPANTS: Patients with a
      clinical diagnosis of skull fracture were identified from the hospitals in
      patient enquiry (HIPE) database. Of 338 patients, 31 (9%) were identified as
      having a temporal bone fracture on high-resolution CT scanning. MAIN OUTCOME AND
      MEASURES: The rate and distribution of each major clinical complications within
      each classification system to establish if either one was more clinically useful.
      RESULTS: Fractures were classified as mixed in 14 (45%), longitudinal in 9 (29%)
      and horizontal in 8 (26%). Alternatively, 2 (7%) were otic capsule violating and
      29 (93%) were otic capsule sparing. Seventeen patients (54.8%) sustained a
      hearing loss. Seven patients (23%) sustained a facial nerve injury. Four (13%)
      developed a cerebrospinal fluid (CSF) leak. Of all clinical findings only
      sensorineural hearing loss occurred significantly more often in the horizontal as
      opposed to the longitudinal group (P = 0.029) and in the otic violating as
      opposed to the otic sparing group (P = 0.013). CONCLUSIONS: We acknowledge that
      the relatively small size of our cohort diminishes the statistical power of our
      conclusions. However, we found that the otic capsule-based classification system
      was not significantly better than the traditional system in predicting the
      likelihood of sustaining specific injuries from fractures of the temporal bone.

PMID- 16911645
TI  - The significance of MRI findings for non-rhinological disease.
AB  - OBJECTIVES: Mucosal changes in the paranasal sinuses are detected in 30-50% of
      scans for non-rhinological disease. This study assesses the relationship between
      symptoms of rhinosinusitis and radiological evidence of sinus pathology in
      patients undergoing magnetic resonance imaging (MRI) scans for unrelated
      pathology. DESIGN: Prospective observational study, evaluating symptoms of
      rhinosinusitis in patients undergoing MRI scanning of the internal acoustic
      meati. A visual analogue scale (VAS) of rhinological symptoms was completed
      immediately before scanning, specifying symptoms present at the time of
      completing the questionnaire. Symptom scores were recorded by one of the
      investigators, blinded to the MRI images. Two investigators independently rated
      sinus mucosal thickening for each scan, both of whom were blinded to the symptom
      scores. Lund and Mackay scoring systems were used for both symptom and
      radiological scores, which were then compared. SETTING: Otolaryngology and
      Radiology Departments in a large teaching hospital. PARTICIPANTS: Fifty
      consecutive patients were recruited over a 2-month period. MAIN OUTCOME MEASURES:
      Visual analogue scale symptom scores were compared with radiological scores for
      sinus mucosal thickening. RESULTS: No statistically significant relationship was
      demonstrated between rhinological symptoms and radiological features suggestive
      of rhinosinusitis in patients undergoing MRI scanning for non-rhinological
      disease. CONCLUSIONS: The relationship between rhinological symptoms and MRI
      findings of sinus pathology is not straightforward. Management decisions should
      be made on the basis of nasal history and endoscopy, rather than radiological
      findings. This is the first study assessing this relationship by documenting
      symptoms on the day of scanning, using a validated scoring system.

PMID- 16911648
TI  - Assessment of subjective scales for selection of patients for nasal septal
      surgery.
AB  - OBJECTIVE: To investigate the use of subjective measures to assist the surgeon in
      patient selection for septal surgery. STUDY DESIGN: Prospective, observational.
      Approved by local ethics committee. SETTING: ENT outpatient department,
      University Hospital of Wales. PARTICIPANTS: Forty-six participants on the waiting
      list for septal surgery for nasal obstruction. MAIN OUTCOME MEASURE: Measurement
      of nasal partitioning of airflow by rhinospirometer (GM Instruments, Scotland),
      subjective scales, and investigator's assessment of septal deviation. RESULTS:
      The subjective scores, and investigator's assessment of septal deviation, were
      compared with the rhinospirometer objective measurements for correlation,
      sensitivity and specificity. The rhinospirometry results showed that 20% of the
      patients on the waiting list had objective measures of partitioning of nasal
      airflow within a normal range for healthy subjects. The ordinal scale proved to
      be more useful than the visual analogue scale for patient selection. The
      subjective scores of airflow partitioning from the double ordinal scale
      correlated well with the rhinospirometry measurements (r = 0.8). The ordinal
      scale also had a sensitivity of 81% and a specificity of 60%. The investigator's
      subjective assessment of septal deviation had a high sensitivity at around 100%
      but had a lower specificity (30%). CONCLUSIONS: The use of a subjective ordinal
      scale to measure partitioning of airflow greatly increased the specificity of
      patient selection and it is proposed that this scale may be useful to the surgeon
      when assessing patients for septal surgery.

PMID- 16911649
TI  - Topical adrenaline in the control of intraoperative bleeding in adenoidectomy: a
      randomised, controlled trial.
AB  - OBJECTIVES: To evaluate the efficacy of topical racemic adrenaline (RA)
      (Micronefrin; Bird Products, Palm Springs, CA, USA) in the control of
      intraoperative bleeding and the prevention of postoperative bleeding, laryngeal
      spasm and postoperative pain in adenoidectomy among children <6 years of age.
      DESIGN: Prospective, randomised, blinded and placebo-controlled trial. SETTING:
      Kanta-Hame Central Hospital, a district referral center in Finland. PATIENTS: A
      consecutive sample of 93 children undergoing outpatient adenoidectomy.
      INTERVENTION: Patients were randomised to receive topical gauze sponges soaked in
      either 1:500 RA or 0.9% sodium chloride (physiological saline) for 3 min after
      adenoidectomy. MAIN OUTCOME MEASURES: Amount of intraoperative bleeding
      (surgeons' subjective estimate), need for additional packings, need for
      electrocautery, laryngeal spasm, postoperative bleeding and pain, duration of
      procedure and duration of patients' stay in the operation room (OR). RESULTS:
      Adrenaline significantly decreased surgeons' subjective estimate of the amount of
      intraoperative bleeding (proportion of patients with significant decrease 67
      versus 21%, P < 0.001), reduced the mean number of packings needed (0.6 versus
      1.2, P < 0.001) and use of electrocautery (22 versus 45%, P = 0.015), and
      shortened the mean duration of the procedure (13 versus 18 min, P = 0.043) and
      the mean stay in the OR (31 versus 35 min, P = 0.058). The impact of adrenaline
      was even more pronounced among patients with extensive adenoids and/or profuse
      intraoperative bleeding. A slight elevation of heart rate was observed more often
      in the adrenaline group (P = 0.043). CONCLUSIONS: Use of topical adrenaline can
      be recommended in adenoidectomy among children. It helps control the
      intraoperative bleeding, reduces the use of electrocautery and shortens the
      durations of procedure and stay in the OR.

PMID- 16911650
TI  - Patients' views on the utility of quality of life questionnaires in head and neck
      cancer: a randomised trial.
AB  - OBJECTIVES: (i) To evaluate head and neck cancer patient perspectives regarding
      the usefulness of quality of life questionnaires in communicating their health
      problems to clinicians and (ii) to identify the quality of life questionnaire
      that head and neck cancer patients find most useful. DESIGN: Randomised
      questionnaire study. Patients completed all four validated head and neck cancer
      quality of life questionnaires - European Organisation for Research and Treatment
      of Cancer (EORTC), Functional Assessment of Cancer Therapy Scale (FACT) HN35,
      Washington quality of life questionnaire, Auckland quality of life questionnaire.
      Order of questionnaire presentation was randomised to counterbalance order
      effects. SETTING: Tertiary referral head and neck cancer centre. PARTICIPANTS:
      Eighty patients diagnosed and treated for head and neck cancer. EXCLUSION
      CRITERIA: blindness, learning difficulties or inability to understand or read
      English. MAIN OUTCOME MEASURES: Patient ratings of perceived usefulness and
      preferences of studied questionnaires. RESULTS: Patients reported high relevance
      to their problems and high ease of understanding of all questionnaires, with FACT
      scoring highest (79% and 89%, respectively); 58% of participants (67%
      respondents) would like to complete a questionnaire in clinic, as it would help
      them describe their health problems to their doctors; 28% of participants did
      not. Almost half preferred a particular quality of life questionnaire, FACT being
      most preferred. Length of questionnaire did not affect reported usefulness, but
      most would prefer a short questionnaire (<20 items). CONCLUSIONS: Patients report
      that head and neck cancer quality of life questionnaires effectively describe
      their health concerns. Most are in favour of completing quality of life
      questionnaires in clinic, as an aid for describing health problems to clinicians.
      There appears to be a difference between clinicians and patients regarding the
      perceived usefulness of quality of life questionnaires in the clinic setting,
      which needs to be highlighted to clinicians.

PMID- 16911651
TI  - A child who snores.

PMID- 16911654
TI  - How we do it: tympanoplasty: are different three- and four-frequency averages
      comparable?
AB  - The results of tympanoplasty may be reported in a variety of ways. Pure-tone
      audiometry underpins reporting, yet there is no constancy in the pure-tone
      threshold average used. We examine the relationship between the 0.5, 1, 2 kHz,
      0.5, 1, 2, 3 kHz and 0.5, 1, 2, 4 kHz pure-tone audiometry averages. Using
      audiometric data collected for 77 patients, we have compared hearing threshold
      using three different frequency averages derived from pure-tone audiometry. The
      0.5, 1, 2 kHz, 0.5, 1, 2, 3 kHz and 0.5, 1, 2, 4 kHz three- and four-frequency
      averages are significantly different, this difference being primarily determined
      by the changes in the 4-kHz threshold. Using an average including 4 kHz results
      in 8% few patients achieving an ABG closure to within either 10 dB or 20 dB. When
      comparing surgical results with others, surgeons should use reports employing
      comparable audiometric measures of analysis.

PMID- 16911655
TI  - How we do it: the viability of free mucosal grafts on exposed bone in lacrimal
      surgery - a prospective study.
AB  - To ascertain viability of free mucosal of grafts on bare bone and degree of
      contracture in vivo. Prospective study to ascertain graft survival where a small
      piece of mucosa, with a single centrally placed prolene suture for future
      identification, removed during endoscopic dacrocystorhinostomy (DCR) was replaced
      to cover exposed bone at the end of the procedure. The presence of the graft and
      the degree of contracture was assessed endoscopically in outpatients at the
      second and fourth weeks. All patients who fulfilled the inclusion criteria who
      underwent DCR in the study period April-October 2002. All the grafts survived
      intact at 4 weeks after the operation. Grafts underwent up to 20% contracture
      over this period. Free mucosal grafts survive well when applied to denuded bone
      in DCR operation.

PMID- 16911656
TI  - How we do it: analysing GP referral priorities: the unforeseen effect of 'Choose
      and Book'.
AB  - The introduction of Choose and Book may have a significant effect on the
      proportion of urgent referrals seen by ENT surgeons. Much of the responsibility
      for prioritisation will be transferred to the GP. Patients who are considered
      urgent by the ENT surgeon will be added to those considered urgent by the GP. Our
      results show that there was little agreement between GPs and ENT surgeon on what
      constitutes an urgent referral. The combined effect of joint prioritisation and
      the removal of the 'soon' category resulted in a 270% increase in 'urgent'
      referrals in our sample. This potentially unforeseen consequence of the Choose
      and Book system should be taken into consideration by ENT departments to allow
      for an expansion of the 'urgent' category.

PMID- 16911657
TI  - How we do it: cost-benefit analysis of implementing a telephone review system in
      an ENT outpatient setting.
AB  - There is an increasing pressure on the National Health Service (NHS) hospital
      consultants to reduce the waiting times. We have used an optional telephone
      review for a certain number of our outpatients so as to reduce the need for their
      in-person attendance. The result of our study, which was conducted in two phases,
      showed that almost half of the telephone follow-up patients (48%) were discharged
      over the phone. There was a direct saving of approximately 30 pounds per patient
      having a telephone follow-up.

PMID- 16911658
TI  - How we do it: an audit of Action on ENT baseline standards in otolaryngology
      departments in England, UK.
AB  - An internet-based audit was conducted to determine how well English
      otolaryngology departments apply Action on ENT baseline clinical and
      administrative standards. A total of 91% (97 of 107) departments responded. Only
      8% of 97 departments met all 23 standards but the majority complied with most
      standards. Microsuction and outpatient endoscopy were almost universally
      available (99% and 97% respectively) and 98% monitored in-patient and day surgery
      activity. Compliance was poor (<60%) for three standards: common waiting lists
      for common conditions (51%), facilities to elicit patient feedback (56%) and the
      inclusion of a treatment plan in the notes (46%). More than one in four
      departments lacked dedicated facilities to treat children or a lead clinician for
      paediatric audiology, despite the Children Acts of 1989 and 2004. It is hoped
      that this audit will help sub-optimal units to correct their deficiencies.

PMID- 16911660
TI  - pH testing in laryngopharyngeal reflux.

PMID- 16911661
TI  - A review of sinonasal outcome scoring systems - which is best?

PMID- 16911662
TI  - Responsiveness requires context.

PMID- 16911664
TI  - Acoustic parameters of snoring sound to compare natural snores with snores during
      'steady-state' propofol sedation.

PMID- 16911666
TI  - A third hand for nasal cautery.

PMID- 16911667
TI  - Hearing loss after spinal anaesthesia: comparison of 22 and 25 G Quincke needles
      in a non-elderly population.

PMID- 16911668
TI  - Warning - when using a Foley catheter for post-nasal space packing fill the
      balloon with water rather than saline.

PMID- 16911669
TI  - Readability of ENT consent form amendments.

PMID- 16911670
TI  - Therapeutic approaches of inhaled veil pins in the Egyptians.

PMID- 16911671
TI  - The Wigan grommet trainer.

PMID- 16911672
TI  - Publish or perish.

PMID- 16911673
TI  - Between-batch variation of calibrator activity can significantly influence
      fluorogenic measurement of thrombin generation.

PMID- 16911674
TI  - Fixed-dose low-molecular-weight heparin, bemiparin, in the long-term treatment of
      venous thromboembolism in patients with transient risk factors in standard
      clinical practice: the FLEBUS study.

PMID- 16911675
TI  - Anticoagulant and anti-inflammatory effects after peritoneal lavage with
      antithrombin in experimental polymicrobial peritonitis.
AB  - BACKGROUND: In sepsis, coagulation inhibition using high-dose systemic
      antithrombin (AT) tends to improve survival. However, systemic AT use is
      complicated by increased risk of bleeding (odds ratio 1,7) and clinically
      important survival increase is seen only in the non-heparinized subgroup. Local
      (intra-abdominal) inhibition of coagulation with AT may be more effective.
      OBJECTIVES: To investigate effects of intra-abdominal high-dose recombinant human
      AT (rhAT) lavage on coagulation and inflammation in experimental polymicrobial
      sepsis. METHODS: Murine cecal ligation and puncture model was used with
      peritoneal lavage after 24 h, containing rhAT (3 IU mL-1) or saline. Clotting
      time, thrombin-antithrombin complexes (TAT), D-dimers, tissue-type plasminogen
      activator and plasminogen activator inhibitor-1 assessed coagulation and
      fibrinolysis responses. Inflammation was assessed by keratinocyte-derived
      chemokine (KC), interleukin-1beta (IL-1beta), IL-6, tumor necrosis factor-alpha
      (TNF-alpha), leukocyte count, myeloperoxidase and bacterial load. RESULTS: rhAT
      lavage prolonged abdominal clotting times and reduced D-dimers and TAT levels,
      indicating inhibited abdominal coagulation. Pulmonary clotting time and D-dimers
      decreased towards normal by rhAT lavage. Abdominal fibrinolysis was reduced after
      rhAT lavage, as were abdominal IL-1beta, KC, leukocytes and bacterial load.
      Pulmonary TNF-alpha, KC, myeloperoxidase and histopathological injury were
      decreased. Survival improved from 62% (saline lavage) to 83% (rhAT lavage,
      P<0.05). CONCLUSIONS: High-dose rhAT lavage inhibited coagulation activation, and
      reduced inflammatory responses in both abdominal and pulmonary compartments,
      ultimately improving survival.

PMID- 16911676
TI  - Polymeric immunoglobulin receptor in regulation of intestinal inflammation.

PMID- 16911677
TI  - Gastroesophageal reflux disease in Asian countries: disorder of nature or
      nurture?
AB  - Gastroesophageal reflux disease (GERD) is less prevalent in Asia than in the
      West, but there is now evidence to suggest that its frequency is rapidly rising
      in Asia. The different prevalence rates reported in various Asian studies may
      represent different points in the 'rising' phase of GERD. The cause for the lower
      but increasing prevalence of GERD in Asia is not known, but genetics and to some
      extent environmental factors, may have initially protected Asians against GERD.
      However, with the recent globalization of economies, the associated lifestyle
      changes in many developing Asian countries may have tipped the balance in favor
      of the development of GERD.

PMID- 16911678
TI  - Hepatitis B and C virus infections and anti-tumor necrosis factor-alpha therapy:
      guidelines for clinical approach.
AB  - Anti-tumor necrosis factor-alpha (TNF) therapy has recently been recognized to be
      associated with activation of hepatitis B virus (HBV) infection, with a
      potentially fatal outcome, mirroring experience in the setting of immune
      suppression and subsequent reconstitution in cancer chemotherapy and
      transplantation. Although there is no current evidence that anti-TNF therapy
      influences the natural history of hepatitis C virus (HCV) infection, the
      involvement of TNF in the pathogenesis of hepatic injury and extrapolation from
      other clinical situations heighten awareness of a potential conflict. Preventive
      strategies should be mandatory. These include screening of all patients for HBV
      and HCV infection prior to commencement of anti-TNF therapy, and active
      monitoring of aminotransferases and, for HBV, viral load during and for 3 months
      after therapy has terminated. Prophylactic or early intervention strategies with
      nucleoside analogs are recommended for patients with evidence of HBV infection.

PMID- 16911679
TI  - Contribution of polymeric immunoglobulin receptor to regulation of intestinal
      inflammation in dextran sulfate sodium-induced colitis.
AB  - BACKGROUND: Inflammatory bowel disease (IBD) affects approximately 4 million
      people worldwide and can be caused by dysregulated mucosal immune responses to
      the intestinal commensal microflora. Immunoglobulin A (IgA) is considered to be
      the principal antibody in intestinal secretions and functions to prevent
      commensals and pathogenic organisms from gaining access to epithelial cell
      surfaces. Immunoglobulin A deficiency in humans has been associated with celiac
      disease and ulcerative colitis. However, the precise role of IgA in the
      pathogenesis of these disorders is yet to be fully understood. METHODS: Mice with
      a targeted disruption in IgA production (IgA(-/-) mice) and polymeric
      immunoglobulin receptor (pIgR(-/-) mice) were analyzed for the contribution of
      secretory immunity in the pathogenesis of dextran sulfate sodium (2.5%)-induced
      colitis. RESULTS: It was found that dextran sulfate sodium-treated pIgR(-/-) mice
      displayed greater loss of bodyweight and had severe clinical illness compared to
      similarly treated IgA(-/-) mice and wild-type animals. Additionally, colonic
      tissues from the pIgR(-/-) mice exhibited progressively and significantly greater
      degrees of mucosal edema, ulceration, crypt abscesses and macrophage infiltration
      when compared to similarly treated IgA(-/-) mice and wild-type animals.
      CONCLUSIONS: The results indicate that secretory immunoglobulins contribute to
      protection of the colonic mucosa against dextran sulfate sodium-induced
      epithelial injury, although the isotype of the secretory immunoglobulin (IgA or
      IgM) may not be a decisive factor in such protection. Collectively, the pIgR
      and/or the secretory component are important for the maintenance of epithelial
      integrity and mucosal homeostasis in the colonic epithelium.

PMID- 16911680
TI  - Comparison of the efficacy of rabeprazole 10 mg and omeprazole 20 mg for the
      healing rapidity of peptic ulcer diseases.
AB  - AIM: Rabeprazole has been known to inhibit H(+)/K(+)-ATPase more rapidly than
      omeprazole, the prototype proton pump inhibitor (PPI). The aim of this study was
      to demonstrate equivalence between low-dose rabeprazole 10 mg and omeprazole 20
      mg for the healing rapidity of active peptic ulcer and for improvement of
      symptoms. Also, the effect of CYP2C19 genotypes on ulcer healing rapidity was
      investigated. METHODS: A total of 112 patients with active peptic ulcer were
      randomized to receive either rabeprazole 10 mg q.d. or omeprazole 20 mg q.d. for
      6 weeks. The remaining ratios (%) and complete healing of the ulcer were
      determined by endoscopy at 1 week and 6 weeks of treatment. The severity of ulcer
      pain was also investigated during treatment. CYP2C19 genotype was determined by
      the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)
      method. RESULTS: The remaining ratio of peptic ulcers after 1 week and the
      complete healing rate after 6 weeks in the rabeprazole versus omeprazole group
      were 45.5% versus 50.3% (P = 0.475) and 80.6% versus 87.0% (P = 0.423),
      respectively. CYP2C19 genotypes had no effect on the remaining ratio of peptic
      ulcers after 1 week and the healing rate of peptic ulcers after 6 weeks in both
      groups. The proportions of patients with symptom improvement or resolution were
      comparable between the two groups. CONCLUSION: Low-dose rabeprazole 10 mg has a
      similar efficacy for the healing rapidity of active peptic ulcer disease and
      symptom improvement compared with standard-dose omeprazole 20 mg.

PMID- 16911681
TI  - Non-steroidal anti-inflammatory drugs have bacteriostatic and bactericidal
      activity against Helicobacter pylori.
AB  - BACKGROUND: Helicobacter pylori infection and non-steroidal anti-inflammatory
      drugs (NSAIDs) are each associated with gastrointestinal mucosal damage, but the
      extent and direction of their interactions remain controversial. Therefore, the
      purpose of the present paper was to examine whether specific NSAIDs inhibit the
      growth of Helicobacter pylori in vitro. METHODS: Sodium salicylate, ibuprofen,
      indomethacin, the selective cyclooxygenase-2 inhibitor NS-398 and two derivatives
      of sulindac sulfoxide were tested against two laboratory strains of H. pylori,
      the mouse-adapted Sydney strain, and against seven fresh clinical isolates of
      Helicobacter pylori. Possible effects on Campylobacter jejuni, Staphyloccoccus
      aureus, Escherichia coli, Salmonella typhimurium, and Shigella boydii were also
      examined. RESULTS: Certain NSAIDs possess antibacterial activity against
      Helicobacter pylori at therapeutically achievable doses; an effect that appears
      to be independent of cyclooxygenase enzymes inhibition. For Helicobacter pylori,
      >90% growth inhibition and bactericidal activity were observed consistently for
      sulindac sulfide at < or =70 microg/mL and sulindac sulfone at < or =175
      microg/mL. The minimal inhibitory concentration against Helicobacter pylori was
      125 microg/mL for ibuprofen, 100 microg/mL for indomethacin and 300 microg/mL for
      NS-398 but much higher concentration of sodium salicylate (4000 microg/mL) and
      sulindac sulfoxide (> or =1250 microg/mL) were required to inhibit the growth of
      Helicobacter pylori. CONCLUSIONS: The decreased prevalence of Helicobacter pylori
      in specimens from some NSAID users and the chemopreventive effects of NSAIDs in
      gastric cancer may be related to inhibition of Helicobacter pylori growth.

PMID- 16911682
TI  - Efficacy of peppermint oil as an antispasmodic during endoscopic retrograde
      cholangiopancreatography.
AB  - BACKGROUND: During endoscopic retrograde cholangiopancreatography (ERCP),
      hyoscine-N-butylbromide (Buscopan) or glucagon is used to inhibit duodenal
      motility. However, they may cause adverse effects. Peppermint oil has an
      antispasmodic effect and is used as a less hazardous antispasmodic during
      colonoscopy and upper gastrointestinal endoscopy. The purpose of the present
      paper was therefore to investigate peppermint as an antispasmodic for ERCP.
      METHODS: Forty patients were enrolled prospectively. They were assigned to four
      groups according to the peppermint oil concentration and site of administration:
      group 1, 20 mL of 1.6% solution around duodenal papilla; group 2, 20 mL of 1.6%
      solution both to the antrum of the stomach and around the duodenal papilla; group
      3, 20 mL of 3.2% solution around the duodenal papilla; and group 4, 3.2% solution
      both to the antrum and around the duodenal papilla. Glucagon or hyoscine-N
      butylbromide was added when duodenal peristalsis was not adequately diminished.
      Sixteen patients undergoing ERCP with glucagon were employed as historical
      controls. RESULTS: The ERCP was attempted in all except one patient in group 2
      who had bleeding from invaded tumor to the duodenum. Peppermint administration
      equally reduced duodenal motility in the groups. Duodenal movement was none or
      mild in 69.2% of patients. The ERCP was successfully performed with peppermint
      alone in 91.4% of patients (37/39). Glucagon or hyoscine-N-butylbromide was
      needed in one patient each in groups 1 and 4. Serious complications related to
      peppermint oil did not occur. Inhibitory effect of peppermint appears to be
      identical to that of glucagon. CONCLUSION: Duodenal relaxation was obtained with
      20 mL of 1.6% peppermint oil solution in the duodenum, but additional
      administration may be required. Peppermint oil is useful as an antispasmodic
      agent for ERCP.

PMID- 16911683
TI  - Suppression of Helicobacter pylori-induced interleukin-8 production in vitro and
      within the gastric mucosa by a live Lactobacillus strain.
AB  - BACKGROUND: Accumulating evidence indicates that interleukin-8 (IL-8) plays a
      major role in the mucosal inflammation caused by Helicobacter pylori infection.
      The purpose of the present study was to examine whether Lactobacillus gasseri
      OLL2716 (LG21) can inhibit the H. pylori-induced production of IL-8. METHODS: A
      coculture system including MKN45 cells, H. pylori, and LG21 was established for
      an in vitro analysis. Biopsy specimens were obtained from H. pylori-infected
      human subjects consisting of 19 men and six women. RESULTS: When LG21 was 1/100
      less than H. pylori in a coculture system, LG21 significantly suppressed both the
      IL-8 mRNA and protein generation in the coculture. Live, but not heat- or UV
      treated LG21, could exert the suppressive effect. However, this amount of LG21
      could not suppress either the adhesion of H. pylori to the cell surface or the IL
      8 production by tumor necrosis factor-alpha, which induces IL-8 generation
      through the activation of the transcription. These results thus suggest that LG21
      suppresses an event leading to IL-8 production, which is specific for H. pylori
      induced IL-8 generation, and this event is located upstream from the IL-8
      transcription but downstream from the adhesion. The measurement of the IL-8 level
      using gastric biopsy specimens from H. pylori-infected subjects demonstrated that
      LG21 also suppresses the production of IL-8 in the gastric mucosa. CONCLUSIONS:
      Live LG21 were found to suppress H. pylori-induced IL-8 production in both a
      gastric cell line and within gastric mucosa.

PMID- 16911684
TI  - Clinical significance of measuring blood coagulation factor XIIIA regularly and
      continuously in patients with Crohn's disease.
AB  - BACKGROUND: The aim of the present paper was to determine the mechanism by which
      the level of coagulation factor XIIIA declines during the active phase of Crohn's
      disease. METHODS: The relationship between the activity of Crohn's disease and
      factor XIIIA was observed in 31 patients with Crohn's disease prospectively. The
      relationship between factor XIIIA and thrombin-antithrombin III complex (TAT),
      factor XIIIA expressed on the surface of peripheral monocytes, was also
      evaluated. RESULTS: During the first year, there were 11 patients with Crohn's
      disease in the active phase and 20 patients who remained in remission. The
      average of the lowest level of factor XIIIA among the patients in the active
      phase was 60.1%. The average of the lowest level of factor XIIIA in patients who
      remained in remission was 78.1% (P = 0.049). Among the 20 patients who remained
      in remission for 1 year, eight patients had factor XIIIA levels below 70%. Six of
      them required surgical enterectomies, on average 2 years and 1 month later.
      However, none of the 12 patients who remained in remission for 1 year and who
      never had factor XIIIA levels <70% had a surgical enterectomy during follow up of
      4 years and 6 months (P = 0.002). The decline of factor XIIIA was not due to
      increased consumption secondary to blood coagulation (TAT), nor was it due to a
      decline in the function of monocytes that produce factor XIIIA. CONCLUSION:
      Factor XIIIA declines during the active phase of Crohn's disease because it might
      be consumed in the repair of injured tissue.

PMID- 16911685
TI  - Secretion of RANTES (CCL5) and interleukin-10 from mesenteric adipose tissue and
      from creeping fat in Crohn's disease: regulation by steroid treatment.
AB  - BACKGROUND: Creeping fat represents a characteristic feature of Crohn's disease
      (CD) and adipose tissue is currently being recognized as a complex compartment
      secreting highly active molecules. Pro- or anti-inflammatory adipose tissue
      derived secretory products (adipocytokines) might play a role in the pathogenesis
      of CD. METHODS: Adipose tissue specimens were obtained from creeping fat
      contiguous to the involved intestine of 10 patients with CD. Mesenteric adipose
      tissue specimens resected in 13 patients with colon cancer (CC) and in seven
      patients with diverticulitis (DIV) served as controls. Three fat tissue specimens
      per well and n = 6-8 wells per patient were incubated ex vivo for 24 h. The
      release of regulated on activation, T-cell expressed and secreted (RANTES) and
      interleukin (IL)-10 into the supernatant was measured by ELISA. RESULTS: Both
      RANTES and IL-10 secretion could be demonstrated from total adipose tissue
      explants. The RANTES secretion is increased from creeping fat in CD (3691 +/- 597
      pg/g fat per 24 h) when compared to mesenteric adipose tissue from patients with
      CC (1690 +/- 191 pg/g fat per 24 h; P < 0.0001) or DIV (1672 +/- 336 pg/g fat per
      24 h; P < 0.0001). In contrast, IL-10 secretion is downregulated significantly
      only in patients with DIV (1418 +/- 180 pg/g fat per 24 h; P = 0.016) when
      compared to CC patients (2368 +/- 259 pg/g fat per 24 h). Crohn's disease
      patients receiving steroids had a higher secretion rate of RANTES and IL-10.
      CONCLUSIONS: Both RANTES and IL-10 secretion can be detected from mesenteric
      adipose tissue and from creeping fat. The elevated RANTES and IL-10 secretion
      from creeping fat in CD is not due to a CD-specific effect but caused by steroid
      treatment.

PMID- 16911686
TI  - Vascular endothelial growth factor secretion from mesenteric adipose tissue and
      from creeping fat in Crohn's disease.
AB  - BACKGROUND: Creeping fat represents a characteristic feature of Crohn's disease
      (CD), and adipose tissue secretes adipocytokines and chemokines/growth factors
      such as vascular endothelial growth factor (VEGF). Because VEGF serum levels and
      mucosal VEGF expression is elevated in CD patients, the aim of the present paper
      was to investigate creeping fat-derived VEGF secretion in CD. MATERIAL AND
      METHODS: Adipose tissue was obtained from creeping fat of 10 patients with CD.
      Mesenteric adipose tissue was resected from 13 patients with colon cancer (CC)
      and from seven patients with diverticulitis (DIV). Three fat tissue specimens per
      well, and several wells (6-8) per patient were incubated ex vivo for 24 h. The
      release of VEGF into the supernatant was measured by ELISA. RESULTS: There was
      stable VEGF secretion from mesenteric adipose tissue of patients with CC or DIV
      and from creeping fat of patients with CD. Whereas the VEGF secretion rate was
      not different between patients with CD (465 +/- 98 pg/g fat per 24 h) and CC (399
      +/- 48 pg/g fat per 24 h), VEGF secretion was significantly reduced in patients
      suffering from DIV (115 +/- 41 pg/g fat per 24 h; P < 0.0001 and P = 0.001,
      respectively). The CD patients treated with steroids had significantly lower VEGF
      secretion rates (294 +/- 42 pg/g fat per 24 h) than CD patients not receiving
      steroids (607 +/- 105 pg/g fat per 24 h; P = 0.001). CONCLUSIONS: Creeping fat is
      an important source of VEGF secretion. The characteristics of the inflammatory
      changes in CD might be due to the lack of VEGF downregulation that is seen in
      DIV.

PMID- 16911687
TI  - Does the pancreas move with respiration?
AB  - BACKGROUND AND AIM: The pancreas is a retroperitoneal organ and has been
      classically considered to be immobile on respiration. Recent radiological studies
      assessing the mobility of the pancreas have challenged this traditional concept.
      The present study was conducted to assess the movement of pancreas with
      respiration using fluoroscopy, a simple and inexpensive method. METHODS: Patients
      with chronic pancreatitis who had either pancreatic calcification evident on
      fluoroscopy or an indwelling pancreatic duct stent were studied. The movement of
      the pancreas was assessed under fluoroscopy by measuring the displacement of the
      stent or calcification in relationship to the spine in maximum inspiration
      followed by maximum expiration. RESULTS: Twenty-two patients (mean age 35.45 + or
      - 11.29 years, 17 men) with chronic pancreatitis were included in the study. Ten
      patients had pancreatic calcification and 12 had an indwelling pancreatic duct
      stent (two in the dorsal duct, 10 in the ventral duct). In all patients, the
      pancreas moved downward in the craniocaudal direction on deep inspiration.
      Pancreatic excursion from maximum inspiration to maximum expiration ranged from
      0.1 to 3.4 cm. In addition, a medial movement of the head of pancreas was also
      noted in most of the patients. On univariate analysis, no association was found
      between the range of movement and the age or sex of the patient, duration or
      etiology of disease, presence or absence of calcification, severity of ductal
      changes of chronic pancreatitis and the length or diameter of the pancreatic
      stent placed. CONCLUSION: The pancreas moves craniocaudally with respiration and
      the head moves medially on inspiration.

PMID- 16911688
TI  - Therapeutic effects of 10 mg/day rabeprazole administration on reflux esophagitis
      was not influenced by the CYP2C19 polymorphism.
AB  - BACKGROUND: The acid suppressive effects of omeprazole (OPZ) and lansoprazole
      (LPZ) are influenced by the CYP2C19 polymorphism. On the other hand, some
      investigators have reported that acid suppressive effect of rabeprazole (RPZ) was
      not significantly affected by CYP2C19. The present study was designed to
      investigate whether the CYP2C19 genotype is related to the healing of reflux
      esophagitis (RE) in treatment with RPZ 10 mg. METHODS: One hundred and three
      Japanese patients with RE were treated with daily oral administration of 10 mg
      RPZ. At 4 and 8 weeks after the start of treatment, healing of RE was evaluated
      endoscopically. The CYP2C19 genotype was investigated before the treatment.
      RESULTS: At 4 weeks after the start of treatment, the healing rates for homo
      extensive metabolizer, hetero-extensive metabolizer, and poor metabolizer
      patients were 83.3% (15/18), 77.3% (17/22), and 88.9% (8/9) [corrected]
      respectively, and at 8 weeks after the start of treatment, the healing rates were
      86.1% (31/36), 92.0% (46/50), and 82.4% (14/17), respectively. There were no
      significant differences in the healing rate of RE among the three genotypes at
      either 4 or 8 weeks after the start of treatment. CONCLUSIONS: The therapeutic
      effects of 10 mg/day RPZ administration on RE may be uninfluenced by the CYP2C19
      polymorphism.

PMID- 16911689
TI  - Molecular epidemiology of hepatitis A virus in Brazilian Amazon.
AB  - BACKGROUND: Hepatitis A virus (HAV) is highly endemic in the Amazon. However, few
      data are available regarding HAV genotypes circulating in this region of the
      world. The aim of the present study was to characterize genetically HAV isolates
      circulating in the Brazilian part of the Amazon. METHODS: Blood samples were
      collected from 134 IgM anti-HAV positive patients (sporadic cases). Viral RNA was
      extracted and the virion protein (VP)1/2A junction region of the HAV genome was
      successfully amplified by reverse transcription-polymerase chain reaction for 81
      samples (60.4%). Nucleotide sequences (210 bp) of the 81 isolates were
      determined. RESULTS: All HAV samples were from genotype I, with 78 (96.3%)
      belonging to subgenotype IA and three (3.7%) to subgenotype IB. By phylogenetic
      analysis, it was shown that 72/78 of the subgenotype IA isolates formed a cluster
      separated from the other South American HAV isolates previously characterized.
      CONCLUSION: The present study provides valuable new data on the genetic
      relatedness of HAV from the Amazon. Subgenotype IB circulates in the Brazilian
      Amazon but the predominant genotype is 1A, similar to what occurs in most South
      American countries.

PMID- 16911690
TI  - Generation and characterization of a single-gene mouse-human chimeric antibody
      against hepatitis B surface antigen.
AB  - BACKGROUND: Antibody against hepatitis B surface antigen (HBsAg) is used for
      passive immunotherapy in certain cases of hepatitis B infection. The authors have
      earlier reported a high-affinity mouse monoclonal (5S) against HBsAg. However,
      this mouse antibody cannot be used for therapeutic purposes because it may elicit
      antimouse immune responses. Chimerization by replacing mouse constant domains
      with human ones can reduce the immunogenicity of this antibody. METHODS: A single
      chain variable fragment (scFv), derived from the mouse monoclonal 5S, was fused
      with the fragment crystallisable (Fc) fragment of human IgG1. The scFv region is
      expected to bind to the antigen, whereas the Fc fragment can provide the effector
      functions required for virus neutralization. This chimeric molecule was expressed
      in Chinese hamster ovary (CHO) cells in serum-free medium. It was purified by
      affinity chromatography and characterized by in vitro binding studies. RESULTS:
      Purification and characterization indicated that this chimeric scFv-Fc fusion
      protein is secreted as a disulfide-linked, glycosylated, homodimeric molecule.
      The yield of the purified chimeric antibody was approximately 4.6 mg/L. In vitro
      analyses confirmed that this chimeric molecule retained the high affinity and
      specificity of the original mouse monoclonal. CONCLUSION: Because it is a single
      gene product, this chimeric scFv-Fc has the advantage of stable expression. Being
      chimeric and bivalent, it is expected to be less immunogenic and therefore
      suitable for further in vivo studies on virus neutralization.

PMID- 16911691
TI  - Presence of antimitochondrial autoantibodies in patients with autoimmune
      hepatitis.
AB  - BACKGROUND AND AIM: Antimitochondrial autoantibodies (AMA) are known to be a
      hallmark of primary biliary cirrhosis, and it has been suggested that AMA play a
      crucial role in generating biliary changes. Biliary tract lesions are not
      uncommon in patients with autoimmune hepatitis (AIH) and previous works have
      demonstrated that AMA are occasionally detectable in sera of patients with AIH.
      Therefore, the role of AMA as a cause of bile duct lesions in AIH livers should
      be addressed. The aim of the present study was to determine whether the presence
      of AMA is associated with clinical features, especially the occurrence of bile
      duct lesions, in patients with AIH. METHODS: Forty-one patients diagnosed as
      having AIH according to the revised scoring system of the International
      Autoimmune Hepatitis Group were enrolled in this study. Clinical data were
      retrospectively reviewed, and histological findings of the liver were
      investigated. AMA reactivity was determined by immunoblotting using beef heart
      mitochondria as antigens. RESULTS: Although not found in any enrolled patient by
      conventional indirect immunofluorescence, AMA were detectable in 14 out of 41
      patients (34%). Clinical parameters including biochemistry, autoantibody profile,
      and responses to treatment were similar irrespective of AMA status. Bile duct
      lesions were noted in 14/14 (100%) and 23/27 (85%) of AMA-positive and -negative
      patients with AIH, respectively (P = 0.134). There was no statistically
      significant difference in the grade of inflammation or stage of fibrosis between
      the two groups. CONCLUSION: Antimitochondrial autoantibodies were found to be
      present in sera of patients with AIH more frequently than expected, even at very
      low titer. However, clinical features and histological findings of AIH were not
      influenced by the AMA status.

PMID- 16911692
TI  - Factors influencing the prevalence of gallstones in liver cirrhosis.
AB  - BACKGROUND AND AIMS: To investigate the prevalence of gallstone disease in
      Chinese patients with liver cirrhosis and to identify risk factors for
      cholelithiasis. METHODS: Blood samples were tested and ultrasonographic
      examination of the upper abdomen was conducted to observe the prevalence of
      gallstones in 90 compensated cirrhotic patients (Child-Pugh A), 180 decompensated
      cirrhotic patients (Child-Pugh B, C) and 300 controls. Risk factors for gallstone
      formation (age, sex, pregnancy, family history) and the characteristics of liver
      cirrhosis (Child class, inside diameter of portal vein), and gallbladder (wall
      thickness) were assessed. RESULTS: Gallstones were found more often in cirrhotic
      patients (23.7%) than in controls (7.33%, P < 0.001). The prevalence of
      gallstones in decompensated cirrhotic patients was higher than that of the
      compensated cirrhotic patients (P < 0.001). Advanced age, female sex, family
      history of gallstones, gallbladder wall thickness 4 mm or greater and inside
      diameter of portal vein 13 mm or greater were significantly associated with
      gallstone disease in patients with liver cirrhosis. Multivariate analysis
      revealed that age (P < 0.001), sex (P = 0.0005) and thickness (4 mm or greater)
      of the gallbladder wall (P = 0.0064) were independently associated with gallstone
      disease in such patients. CONCLUSIONS: This study confirms the high prevalence of
      cholelithiasis in liver cirrhosis. Age and sex are risk factors for gallstones
      and gallbladder wall thickness could be an additional risk factor for the
      development of gallstone in patients with liver cirrhosis.

PMID- 16911693
TI  - Hyaluronic acid levels can predict severe fibrosis and platelet counts can
      predict cirrhosis in patients with nonalcoholic fatty liver disease.
AB  - BACKGROUND AND AIM: Nonalcoholic fatty liver disease (NAFLD) represents a
      spectrum of liver disease from simple steatosis to cirrhosis. Therefore, markers
      for predicting NAFLD with advanced fibrosis are needed. The aim of this study was
      to establish non-invasive predictive markers of liver fibrosis in NAFLD. METHODS:
      One hundred and forty-eight patients were diagnosed as having biopsy-proven
      NAFLD. In order to separately identify severe fibrosis (bridging fibrosis plus
      cirrhosis) and cirrhosis, the patients were analyzed twice: first, as mild
      fibrosis versus severe fibrosis; and second, as non-cirrhosis versus cirrhosis.
      Univariate and multivariate analyses were conducted. The diagnostic ability to
      detect severe fibrosis and cirrhosis was assessed by the area under the receiver
      operating characteristic curve. The cut-off values of serum markers to detect
      severe fibrosis and cirrhosis were determined. RESULTS: Hyaluronic acid was
      selected as a predictive marker for severe fibrosis. A cut-off value of 42 ng/mL
      of hyaluronic acid had a 100% predictive value for patients free of severe
      fibrosis and was associated with an optimal combination of sensitivity (100%, 95%
      confidence interval [CI] 90-100%) and specificity (89%, 95%CI 80-94%). The
      platelet count was found to be an independent predictor of cirrhosis. A cut-off
      value of 16 x 10(4)/microL for the platelet count was associated with an optimal
      combination of sensitivity (100%, 95%CI 82-100%) and specificity (95%, 95%CI 90
      98%). CONCLUSIONS: Hyaluronic acid levels can accurately identify NAFLD patients
      with severe fibrosis, and the platelet count can identify NAFLD patients with
      cirrhosis. Thus, these markers offer a good guideline for the assessment of
      hepatic fibrosis in the many patients with NAFLD.

PMID- 16911694
TI  - Mutation of keratin 8 in patients with liver disease.
AB  - BACKGROUND: Epithelial tissues of the gastrointestinal tract and the liver
      express predominantly cytokeratin 8 and cytokeratin 18. In vitro experiments and
      animal studies have demonstrated a protective influence of keratin 8 and keratin
      18 against toxic damage of hepatocytes. A specific mutation of keratin 8 (G61C)
      was found to be a genetic risk factor for the development of cryptogenic liver
      cirrhosis. The purpose of the present paper was therefore to determine the
      prevalence of cytokeratin 8 (G61C) and cytokeratin 18 mutations (Y53H) in
      patients with liver disease. METHODS: Overall 152 patients (male, n = 93, 61%;
      female, n = 59, 39%) were included in the present study. The 152 patients
      consisted of 107 patients with liver disease (70.4%; male, n = 71, 66.4%; female,
      n = 36, 33.6%) and 45 control patients (29.6%; male, n = 22, 48,9%; female, n =
      23, 51,1%) without liver disease. Of the patients with liver disease 46 had
      alcoholic liver disease; 25, chronic hepatitis C; 15, cryptogenic liver disease;
      and 21, other liver diseases of various etiologies. Cytokeratin 8 and 18
      genotypes were specified by polymerase chain reaction (PCR) amplification and
      direct sequence analysis was used to detect the previously described mutations in
      cytokeratin 8 (G61C) and in cytokeratin 18 (Y53H). RESULTS: Four out of 152
      patients (male n = 2, female n = 2) with a mutation (G61C) in cytokeratin 8 were
      found. The etiology was alcoholic liver disease (n = 1), cryptogenic liver
      disease (n = 1) and idiopathic liver disease with minimal changes in liver biopsy
      (n = 1). Also, one out 45 disease control patients with an adenoma of the colon
      but without liver disease was found to carry the mutation G61C of cytokeratin 8.
      Therefore, the mutation G61C in cytokeratin 8 was found in 2.8% of patients with
      liver disease and in 2.2% of control patients without liver disease. Two of 15
      patients (13.3%) with cryptogenic liver disease had the mutation G61C in
      cytokeratin 8 (P = 0.069 vs patients with non-cryptogenic liver disease). In the
      152 patients studied, no mutation in cytokeratin 18 was found. DISCUSSION: The
      mutation G61C in the cytokeratin 8 gene was found in one patient with alcoholic
      liver disease and in two patients with liver disease of unknown etiology. Also,
      one patient without liver disease had the cytokeratin 8 G61C mutation. In
      summary, the cytokeratin 8 mutation G61C, which has been found to be associated
      with cryptogenic liver cirrhosis, was also found in the present patient
      population. However, the clinical relevance is yet to be determined in further
      investigations.

PMID- 16911695
TI  - Clinicopathological study of scirrhous hepatocellular carcinoma.
AB  - BACKGROUND AND AIMS: Scirrhous hepatocellular carcinoma (SHCC) is characterized
      by diffuse fibrosis of the tumor, however, its clinicopathological features are
      not fully clarified. This study aimed to clarify the clinicopathological features
      of SHCC. METHODS: Among 546 consecutively resected HCC without preoperative
      anticancer therapies, 25 SHCC were selected for the study and compared with 521
      cases without scirrhous as the control. RESULTS: SHCC accounted for 4.6% of
      cases. On diagnostic imagings, SHCC was frequently misdiagnosed as
      cholangiocarcinoma (CC), combined HCC-CC or metastatic carcinoma. Overall
      survival rate was significantly higher than the control. The average (+/-SD)
      tumor size of SHCC was 3.4 +/- 1.8 cm without significant difference to the
      control. The majority of SHCC (88%) were located close to the liver capsule. SHCC
      was characterized by stellate fibrosis (84%), no encapsulation (100%), no
      necrosis and hemorrhage (100%), intratumoral portal tracts (80%), remarkable
      lymphocyte infiltration (84%), clear cell change (84%), and hyaline bodies (52%).
      The number of alpha-smooth muscle actin-positive myofibroblast-like cells
      (activated stellate cells) in the tumor was about three times more than that in
      the control. Regarding the developmental mechanism of scirrhous change, a close
      correlation with unique tumor location and activation of stellate cells was
      suggested. CONCLUSIONS: SHCC presents with characteristic clinicopathological
      features and the recognition of SHCC is important for both clinicians and
      pathologists.

PMID- 16911696
TI  - High dose vitamin K3 infusion in advanced hepatocellular carcinoma.
AB  - BACKGROUND AND AIM: The survival of patients with unresectable advanced
      hepatocellular carcinoma (HCC) with portal vein thrombosis is dismal. Current
      therapeutic options have limited efficacy. Vitamin K has been shown to have
      antitumor effect on HCC cells both in cell lines and patients with advanced HCC.
      The aim of this study was to assess the clinical efficacy of high dose vitamin K3
      in the treatment of advanced HCC with portal vein thrombosis. METHODS: Forty-two
      consecutive patients with advanced HCC (Stage C according to BCLC staging system)
      with portal vein thrombosis were randomized into two groups: (i) high dose
      vitamin K3 (n = 23); and (ii) placebo (n = 19). The vitamin K3 was administered
      by i.v. infusion of 50 mg/day with daily increase of dose by 50 mg for 6 days,
      followed by 20 mg i.m. twice daily for 2 weeks. RESULTS: Of the 23 patients
      treated with vitamin K, one (4.3%) achieved complete response and three (13%)
      partial response, for a total of four (17.4%) objective responders overall. The
      overall mean survival was 8.9 +/- 8.8 months (median: 6; range 1-37 months) in
      the vitamin K group and 6.8 +/- 5.3 months (median: 5; range 1.5-21 months) in
      the placebo group (P = 0.552). The mean duration of survival was longer in
      patients in the vitamin K group who achieved objective response (22.5 +/- 12.2;
      median: 21; range 11-37 months) as compared to patients not achieving objective
      response (6.1 +/- 4.6; median: 5; range 1-16 months) (P = 0.0.002). Portal vein
      thrombosis resolved with complete patency in one (4.35%) patient. CONCLUSIONS:
      Treatment with high dose vitamin K produces objective response in 17% patients
      with improved survival in patients achieving objective response; however, it does
      not affect the overall survival.

PMID- 16911697
TI  - Lack of detrimental or therapeutic effects of cyclooxygenase inhibition in bile
      duct-ligated rats with hepatic encephalopathy.
AB  - BACKGROUND: The pathogenetic mechanisms of hepatic encephalopathy (HE) are not
      fully understood. Cerebral blood flow regulated by cyclooxygenase (COX) may be
      involved in the development of HE. There are no comprehensive data concerning the
      effects of COX inhibition on HE in chronic liver disease. METHODS: Male Sprague
      Dawley rats weighing 240-270 g at the time of surgery were selected for
      experiments. Secondary biliary cirrhosis was induced by bile duct ligation (BDL).
      Those rats were then divided into two groups to receive i.p. injection of
      indomethacin (5 mg/kg per day) or distilled water for 7 days from day 36 to day
      42 after BDL. The control group consisted of rats receiving a sham operation.
      Severity of encephalopathy was assessed by counts of motor activity. Plasma
      levels of tumor necrosis factor (TNF)-alpha and 6-keto-prostaglandin F(1alpha) (6
      keto-PGF(1alpha)), and liver biochemistry tests were determined after treatment.
      RESULTS: The motor activity in both groups of BDL rats were significantly lower
      than that of the control group (P < 0.001). As compared with the BDL rats treated
      with distilled water, BDL rats treated with indomethacin had significant lower
      levels of 6-keto-PGF(1alpha), but the motor activity, TNF-alpha levels and serum
      biochemistry tests were not significantly different between both BDL groups.
      CONCLUSIONS: Chronic indomethacin administration did not have significantly
      detrimental or therapeutic effects on the severity of encephalopathy in BDL rats.

PMID- 16911698
TI  - Polymorphisms in the promoter region of the angiotensinogen gene are associated
      with liver cirrhosis in patients with chronic hepatitis B.
AB  - BACKGROUND AND AIMS: It is known that the renin-angiotensin system (RAS)
      regulates fibrosis. Polymorphisms in the genes of the RAS may contribute to the
      outcome of liver cirrhosis. Angiotensinogen (AGT), mainly produced in the liver,
      is the substrate of renin. The aim of this study was to determine whether
      polymorphisms in the promoter region of the AGT gene are associated with liver
      cirrhosis in patients with chronic hepatitis B. METHODS: Restriction fragment
      length polymorphism PCR was used to study polymorphisms in the promoter region of
      the AGT gene in patients with liver cirrhosis and in a control population. Four
      polymorphisms were assayed: G-217A, G-152A, A-20C and A-6G. RESULTS: A
      statistically significant relationship was seen between polymorphisms of the AGT
      core promoter region and liver cirrhosis in patients with chronic hepatitis B (A
      20C, P = 0.007; A-6G, P = 0.042). However, the distributions of the AGT-217 and
      AGT-152 genotypes were not significantly different from the control population (P
      = 0.615 and P = 0.170, respectively). CONCLUSIONS: Polymorphisms of the core
      promoter region of the AGT gene (AGT-20 and AGT-6) were associated with liver
      cirrhosis in patients with chronic hepatitis B.

PMID- 16911699
TI  - Education and imaging. Gastrointestinal: celiac axis compression syndrome.

PMID- 16911700
TI  - Education and imaging. Gastrointestinal: Fitz-Hugh-Curtis syndrome.

PMID- 16911701
TI  - Education and imaging. Gastrointestinal: malignant peritoneal mesothelioma.

PMID- 16911702
TI  - Education and imaging. Gastrointestinal: MALT lymphoma of the terminal ileum.

PMID- 16911703
TI  - Education and imaging. Hepatobiliary and pancreatic: oral therapy for pancreatic
      duct stones.

PMID- 16911704
TI  - Multiple hepatic nodules: rare manifestation of clonorchiasis.
AB  - A 38-year-old man was admitted due to intermittent right upper quadrant pain for
      1 month. Leukocytosis with marked eosionphilia and elevated serum alkaline
      phosphatase were noted. Stool examinations revealed no parasites or ova.
      Ultrasonography and computed tomography disclosed multiple hepatic tumors. Biopsy
      of the hepatic tumor was performed due to non-conclusive imaging studies and
      revealed eosinophil infiltration in portal areas only. Endoscopic retrograde
      cholangiography showed mild dilatation with irregularity of bilateral
      intrahepatic ducts, compatible with chronic cholangitis. Bile was aspirated and
      biliary lavage with normal saline was performed during endoscopy-guided biliary
      cannulation. Microscopic examination of the aspirate showed the characteristic
      ova of Clonorchis sinensis. The patient received Praziquantel therapy for 1 day.
      Abdominal pain reduced in intensity gradually. Eosinophilia and multiple hepatic
      lesions resolved after adequate treatment of Clonorchis sinensis. The rare
      manifestation of multiple hepatic tumors in Clonorchis sinensis should be
      differentiated from other primary or metastatic neoplasms, while biliary lavage
      for parasite ova is a valuable diagnostic tool when stool examination is
      negative.

PMID- 16911705
TI  - Peptide YY3-36 and pancreatic polypeptide suppress food intake.

PMID- 16911706
TI  - Gastrointestinal obstruction caused by the spontaneously detached Brunner's gland
      hamartoma of the duodenum.

PMID- 16911707
TI  - Endoscopic epinephrine injection induced amaurosis fugax.

PMID- 16911708
TI  - Usefulness of perfusion computed tomography for early detection of pancreatic
      ischemia in severe acute pancreatitis.

PMID- 16911710
TI  - Litter characteristics of gilts artificially inseminated with transforming growth
      factor-beta.
AB  - PROBLEM: Semen is a rich source of transforming growth factor-beta (TGF-beta) and
      it has been proposed that this molecule promotes embryonic survival by modifying
      immune responses to promote tolerance toward paternal antigens and by inducing
      release of cytokines that promote embryonic development. The role of TGF-beta was
      tested using pigs by evaluating whether its addition to washed sperm improves
      conceptus survival and fetal growth. METHODS OF STUDY: At estrus, gilts were
      artificially inseminated twice at 12-hr intervals with 100 mL of either washed
      semen resuspended in a commercial semen extender supplemented with 2 mg/mL of
      gelatin or washed semen in the same extender containing 65 ng/mL of TGF-beta1.
      Three boars were used as semen donors. At day 80 (+/-4 days) of gestation, gilts
      were sacrificed and reproductive tracts harvested. RESULTS: Treatment had no
      effect (P > 0.10) on total or live fetuses per litter, implantation rate, fetal
      survival or percentage of corpora lutea resulting in live fetuses at day 80.
      Insemination with TGF-beta1 also did not affect total or average fetal weight or
      total placental weight. There was a tendency (P = 0.09) for average placental
      weight of live fetuses to be lower for pregnancies established in gilts treated
      with TGF-beta1. Also, placental efficiency (mass of fetus/mass of placenta) was
      greater (P < 0.05) for pregnancies established in gilts treated with TGF-beta1.
      The high fertility in control gilts (80% implantation rate and 11.5 live fetuses
      per litter) is indicative that soluble seminal factors are not necessary for the
      establishment of pregnancy. CONCLUSIONS: Within the ranges tested, concentration
      of TGF-beta in the fluid phase of the inseminate is not an important determinant
      of conceptus survival or fetal and placental growth to day 80 of gestation in the
      pig.

PMID- 16911711
TI  - Transfusion-related risks of intradermal allogeneic lymphocyte immunotherapy:
      single cases in a large cohort and review of the literature.
AB  - PROBLEM: Lymphocyte immunotherapy (LIT) is applied in infertility treatment.
      Moreover, it has been suggested for prevention of rhesus D-hemolytic disease and
      as a vaccine for reduction of human immunodeficiency virus-1 susceptibility.
      Although transfusion-related problems have been rarely reported they were a
      matter of debate. Here we discuss extensive single-center experience with
      intradermal LIT for implantation failure and recurrent miscarriages. METHOD OF
      STUDY: Retrospective 2- to 3-year follow-up of in vitro fertilization couples
      treated during 1996-2002 (feedback 2,848/3,041 = 93%), registering 930
      deliveries. Prospective survey for acute reactions for 2000-2003 (feedback
      2,687/3,246 = 83%). Review of the literature. RESULTS: Infections of the patient
      and transplant rejection later in life are minor residual risks. Post-transfusion
      purpura was suspected once but not verified. Anaphylaxis or malignancy were not
      promoted. Fetal/newborn alloimmune disease (severe hemolytic disease,
      thrombocytopenia, neutropenia) were not observed. CONCLUSION: Based on
      microbiological, immunological, and hematological testing the risks of
      intradermal LIT are low.

PMID- 16911712
TI  - Human leukocyte antigen F protein is expressed in the extra-villous trophoblasts
      but not on the cell surface of them.
AB  - PROBLEM: Human leukocyte antigen (HLA)-F together with other class 1b HLAs may
      play a pivotal role in immunological interaction at feto-maternal interface.
      However, it is not elucidated whether HLA-F is expressed on cell surface of extra
      villous trophoblasts (EVTs). METHOD OF STUDY: The localization of HLA-F in
      placenta of each trimester was investigated by immunohistochemistry. The
      expression modality of HLA-F molecule was compared with that of HLA-G in cultured
      EVTs using flowcytometry. RESULTS AND CONCLUSION: In immunohistochemical study,
      remarkable staining for HLA-F was confirmed in EVTs throughout gestation. HLA-F
      expression was restricted to be intracellular in cultured EVTs. HLA-F expression
      was increased with time in culture, which was accompanied by the increase of cell
      surface HLA-G. Consequently, HLA-F lacking in cell surface expression on EVTs may
      not contribute to the direct cell-to-cell immune reaction but might work
      supportively modifying the function of HLA-G.

PMID- 16911713
TI  - Polymorphisms in exons 1B and 1C of the type I interleukin-1 receptor gene in
      patients with endometriosis.
AB  - To study possible correlation between the prevalence of polymorphisms in the type
      I interleukin-1 receptor gene and pelvic endometriosis. Genotypes of 223 women
      were analyzed: 109 women with surgically and histologically confirmed
      endometriosis and 114 healthy women. Distributions of two single-base
      polymorphisms of the human interleukin-1 receptor type I (IL-1RI) gene were
      evaluated: PstI, due to a C-->T transition in exon 1B and BsrBI a C-->A
      transition at position 52 in exon 1C. Polymorphisms were detected by polymerase
      chain reaction (PCR) followed by restriction fragment length polymorphism
      analysis (RFLP) resolved on 3% agarose gels stained with ethidium bromide.
      Genotypes for PstI polymorphisms did not differ significantly among control and
      endometriosis (P = 0.058). However, in relation to BsrBI polymorphism, protective
      risk was observed for the development of endometriosis [OR 0.39-IC 95% (0.2
      0.9)]. BsrBI heterozygote genotype (C/A) showed protective effect against
      endometriosis development.

PMID- 16911714
TI  - Butyrylcholinesterase activity in gestational diabetes: correlation with
      lymphocyte subpopulations in peripheral blood.
AB  - PROBLEM: Inefficient clearance of pregnancy-threatening toxins may contribute to
      gestational diabetes (GD) and Type II diabetes mellitus (DM) through mechanisms
      involving immune dysregulation. METHOD OF STUDY: Peripheral venous blood from
      pregnant Kuwaiti women in third trimester, including 15 GD and 17 DM patients, 14
      healthy pregnant (HP) and eight non-pregnant subjects, was analyzed by two-color
      flow cytometery for number and percentage representation of T lymphocytes.
      Buterylcholinesterase (BuChE) activity was measured using buterylthiocholine
      iodide and spectrophotometry. RESULTS: Relative to HP, GD patients exhibited
      higher ratios of activated and memory phenotypes, including CD4+ CD25+ (P <
      0.01), CD4+ HLA-DR (P < 0.05) and CD4+ CD45RO+ (P < 0.05) cells. Serum BuChE
      activity exhibited positive correlation within the HP cohort with CD4+ CD25+ (P <
      0.05), but not in GD and DM cohorts. CONCLUSIONS: Positive correlation between
      BuChE and a (presumptive) 'regulatory' T-cell phenotype in HP, but not GD or DM
      may indicate existence of protective detoxification mechanisms against oxidative
      stress in normal pregnancies.

PMID- 16911715
TI  - Natural killer, natural killer T, helper and cytotoxic T cells in the decidua
      from sporadic miscarriage.
AB  - PROBLEM: The aim of this cohort study was to assess natural killer (NK) cell and
      natural killer T (NKT) cell populations and cytokine expressions of helper T (Th)
      and cytotoxic T (Tc) cells in the decidua of sporadic miscarriage (MS) and
      induced abortion (IA). METHODS: The deciduae were obtained from consecutive 40
      women whose pregnancies ended in the first trimester MS, and the fetal chromosome
      karyotypes were analyzed. The cell populations were measured by flow cytometry.
      RESULTS: No significant differences in NK cell or NKT cell percentages were found
      among MS with normal chromosome karyotype (MSNK, n = 14), MS with abnormal
      karyotype (MSAK, n = 26) and IA (n = 14). Interferon (IFN)-gamma(+) cell
      percentage and interleukin (IL)-4(+)/tumor necrosis factor (TNF)-alpha(+) ratio
      of Th cells in MS groups were increased, while IL-4(+) cell percentage, IL
      4(+)/IFN-gamma(+) and IL-4(+)/TNF-alpha(+) ratios of Tc cells in MS groups were
      decreased as compared with those in IA. No significant difference in these
      parameters between MSNK and MSAK was found. CONCLUSIONS: These results suggested
      that Tc1 predominance existed in the decidua of MS. Th1 predominance was not
      found in MSNK.

PMID- 16911716
TI  - Cytokines regulate matrix metalloproteinases in human uterine endometrial
      fibroblast cells through a mechanism that does not involve increases in
      extracellular matrix metalloproteinase inducer.
AB  - PROBLEM: Endometriosis is the presence of ectopic uterine endometrial tissue in
      the peritoneal cavity. Peritoneal fluid samples of women with endometriosis show
      elevated interleukin-1 (IL-1)beta, tumor necrosis factor (TNF)-alpha and
      transforming growth factor (TGF)-beta(1) levels, indicating that an altered
      immune system may play an important role in the pathogenesis of endometriosis.
      The invasion of ectopic endometrium into peritoneal mesothelium requires matrix
      metalloproteinases (MMPs) for tissue remodeling. Several MMPs are differentially
      expressed in human uterine endometrium with menstrual endometrium showing the
      highest level of expression. MMPs are stimulated by cytokines and also by the
      protein Extracellular Matrix Metalloproteinase Inducer (EMMPRIN). METHOD OF
      STUDY: To determine the role of cytokines in ectopic endometrial invasion, we
      investigated whether cytokines could regulate MMP production by endometrial
      fibroblast cells and whether this stimulation occurred through an effect on
      EMMPRIN expression. Human uterine fibroblasts (HUF) were treated with IL-1beta,
      TGF-beta(1) and TNF-alpha in a dose dependent and time dependent manner (C, 0.1,
      1, 10 ng/mL IL-1beta or TGF-beta(1); C, 2, 10, 50 ng/mL TNF-alpha) for 0, 6, 12,
      and 24 hr. Cell conditioned medium samples were collected and concentrated at
      each timepoint for immunoblot analysis. Cellular RNA was collected for real time
      PCR analysis of MMPs-1, -2, -3 and EMMPRIN mRNA levels. RESULTS: Our results
      showed that IL-1beta stimulated MMP-1 protein secretion and mRNA levels in a time
      dependent manner (P < 0.05), MMP-2 mRNA in a time dependent manner and MMP-3 in a
      time and dose dependent manner. TNF-alpha stimulated MMP-1 and -3 protein
      secretion in a time dependent manner and stimulated MMP-1, -2 and -3 mRNA levels
      in a time dependent manner (P < 0.05). Neither IL-1beta nor TNF-alpha treatment
      affected MMP-2 protein secretion. TGF-beta(1) inhibited MMP-1 and MMP-2 mRNAs at
      the highest treatment dose after 24 hr but there was no effect on protein
      secretion. TGF-beta(1) exerted no effect on MMP-3 mRNA or protein secretion (P <
      0.05). Neither of the cytokines affected EMMPRIN protein or mRNA levels but the
      10 ng/mL TGF-beta(1) treatment did cause a reduction in EMMPRIN mRNA levels.
      CONCLUSIONS: These data show that elevated cytokines may play a role in the
      establishment of ectopic endometrium in the peritoneal cavity by stimulating MMPs
      to remodel the mesothelial lining of the peritoneum thus allowing for tissue
      invasion. The stimulation of MMPs by cytokines occurred without any change in
      EMMPRIN expression whereas the inhibitory effect of TGF-beta(1) involved a
      reduction in EMMPRIN mRNA levels.

PMID- 16911717
TI  - Ensuring that addiction science is deserving of public trust.

PMID- 16911718
TI  - Alcohol-related injury and the emergency department: research and policy
      questions for the next decade.

PMID- 16911719
TI  - Drink driving and the regulates of drinking: when will governments learn?

PMID- 16911720
TI  - The legitimacy of addiction treatment in a world of smart people.
AB  - AIM: This paper discusses what type of legitimacy underpins addiction treatment
      in contemporary western societies. METHOD: Broad review of the relevant
      literature. CONCLUSIONS: The legitimacy of professional interventions and the
      future of service provision will depend largely on the relationship between the
      professional and the lay referral system. These in turn are intertwined with
      macro-societal changes. The basic categories in this relationship are, on one
      hand, the idea of evidence-based practice (i.e. the notion of using the most
      accurate scientific support for the choice of treatment interventions), and on
      the other hand the consumer perspective, which conceptualizes addiction treatment
      as an interactive process between the treatment provider and the consumer. The
      acceptance of addiction treatment depends in most cases on the client who chooses
      from a whole range of informal and formal problem solutions. To an extent,
      experts are thus controlled by their lay counterparts and need their consent to
      operate and succeed. This process is complicated by the trend towards evidence
      based practice, which demands transparency and rigorous procedures and carries
      with it the basis for distrust in expert knowledge by displaying openly that
      every statement of fact is open to revision, and thus, to a certain extent,
      characterized by uncertainty.

PMID- 16911721
TI  - Closing remarks: Swimming to the horizon--reflections on a special series.

PMID- 16911722
TI  - The origin of MDMA (ecstasy) revisited: the true story reconstructed from the
      original documents.
AB  - BACKGROUND: Little is known about the origin of methylenedioxymethamphetamine
      (MDMA, ecstasy). The most commonly repeated statement in the medical literature
      is that MDMA was synthesized by the German pharmaceutical company Merck in 1912
      in order to develop an appetite suppressor. AIM: To reconstruct the true story of
      the first known description of MDMA at Merck using the original documents.
      METHODS: A systematic analysis of the original documents in Merck's historical
      archive in Darmstadt, Germany, was conducted (years 1900-60). RESULTS: There were
      no indications for plans to develop an appetite suppressant at Merck between 1900
      and 1960. Although MDMA was, in fact, first synthesized at Merck in 1912, it was
      not tested pharmacologically because it was only an unimportant precursor in a
      new synthesis for haemostatic substances. The new pathway was patented in order
      to evade an existing patent by a local competitor. MDMA was called
      "Methylsafrylamin" in 1912. In 1927 and 1959, the pharmacological effects of MDMA
      were studied at Merck, but not in humans. DISCUSSION: A systematic analysis of
      the original documents in the company's archive revealed that uncritical copy
      paste procedures may have contributed to the famous myth that MDMA was patented
      as an appetite suppressor in 1912.

PMID- 16911723
TI  - Antiretroviral treatment for injecting drug users in developing and transitional
      countries 1 year before the end of the "Treating 3 million by 2005. Making it
      happen. The WHO strategy" ("3 by 5").
AB  - OBJECTIVE: To describe and estimate the availability of antiretroviral treatment
      (ART) to injecting drug users (IDUs) in developing and transitional countries.
      METHODS: Literature review of grey and published literature and key informants'
      communications on the estimated number of current/former injecting drug users
      (IDUs) receiving ART and the proportion of human immunodeficiency virus (HIV)
      attributed to injecting drug use (IDU), the number of people in ART and in need
      of ART, the number of people living with HIV/acquired immunodeficiency syndrome
      (AIDS) (PLWHA) and the main source of ART. RESULTS: Data on former/current IDUs
      on ART were available from 50 countries (in 19 countries: nil IDUs in treatment)
      suggesting that approximately 34 000 IDUs were receiving ART by the end of 2004,
      of whom 30 000 were in Brazil. In these 50 countries IDUs represent approximately
      15% of the people in ART. In Eastern European and Central Asia IDU are associated
      with > 80% of HIV cases but only approximately 2000 (14%) of the people in ART.
      In South and South-East Asia there were approximately 1700 former/current IDUs
      receiving ART ( approximately 1.8% of the people in ART), whereas the proportion
      of HIV cases associated to IDU is > 20% in five countries (and regionally ranges
      from 4% to 75%). DISCUSSION: There is evidence that the coverage of ART among
      current/former IDUs is proportionally substantially less than other exposure
      categories. Ongoing monitoring of ART by exposure and population subgroups is
      critical to ensuring that scale-up is equitable, and that the distribution of ART
      is, at the very least, transparent.

PMID- 16911724
TI  - The impact of later trading hours for hotels on levels of impaired driver road
      crashes and driver breath alcohol levels.
AB  - AIM: To examine the impact of later trading hours for licensed hotels in Perth,
      Western Australia on levels of associated impaired driver road crashes and driver
      breath alcohol levels (BALs). DESIGN: Police data on the "last place of drinking"
      for impaired drivers involved in road crashes and their corresponding BALs were
      examined to identify those associated with Perth hotels between 1 July 1990 and
      30 June 1997. During this period, 43 (23%) of the 186 hotels meeting study
      criteria were granted an Extended Trading Permit for 1 a.m. closing (ETP hotels),
      while the rest continued to close at midnight (non-ETP hotels). Time-series
      analyses employing multiple linear regressions were applied to determine whether
      an association existed between the introduction of extended trading and (i)
      monthly levels of impaired driver road crashes associated with ETP hotels and
      (ii) driver BALs associated with ETP hotels. Trends associated with non-ETP
      hotels were included as controls and possible confounders were considered.
      FINDINGS: After controlling for the trend in crash rates associated with non-ETP
      hotels and the introduction of mobile police breath testing stations to Perth
      freeways, a significant increase in monthly crash rates for ETP hotels was found.
      This relationship was largely accounted for by higher volumes of high-alcohol
      content beer, wine and spirits purchased by ETP hotels. No relation was found
      between driver BALs and the introduction of ETPs. CONCLUSIONS: Late trading was
      associated with increased levels of impaired driver road crashes and alcohol
      consumption, particularly high-risk alcoholic beverages. Greater numbers of
      patrons and characteristics specific to clientele of hotels which applied for
      late trading hours (i.e. younger age, greater propensity to drunk-drive,
      preference for high-risk beverages) were suggested as having contributed to this
      increase.

PMID- 16911725
TI  - Alcohol drinking pattern and subjective health in a population-based study.
AB  - AIMS: Some patterns of alcohol consumption (e.g. binge drinking, drinking outside
      of meals) have been associated with detrimental effects on health outcomes.
      Subjective health provides a global assessment of health status and is a strong
      predictor of total mortality; however, little is known about its relationship
      with alcohol drinking pattern. The association between several drinking patterns
      (i.e. drinking intensity and frequency, frequency of intoxication, drinking
      outside of meals, and beverage type) and subjective health was examined in a
      random sample of 3586 women and men. DESIGN: A population-based cross-sectional
      study. METHODS: Subjective health was assessed using the physical and mental
      health component summaries of the Short Form-36 health survey questionnaire.
      Alcohol consumption refers to the 30 days before the interview. Analysis of
      covariance compared gender-specific mean scores across alcohol drinking patterns.
      FINDINGS: Overall, non-current drinkers reported poorer physical and mental
      health than life-time abstainers and current drinkers, while no consistent
      differences were found between life-time abstainers and current drinkers. In
      female current drinkers, daily drinking, beer and mixed beverage consumption were
      associated with better mental health. In male current drinkers, moderate alcohol
      consumption (2-2.9 drinks per day), wine and mixed beverage consumption were
      associated with better physical health. Intoxication and liquor consumption were
      associated with poorer mental health in women and poorer physical health in men.
      No consistent associations were found for drinking outside meals. CONCLUSIONS:
      Aspects of drinking pattern may affect subjective health differentially in women
      and men. Overall, intoxication and liquor drinking are associated with poorer
      self-perceived health status than regular, moderate consumption of other
      alcoholic beverages.

PMID- 16911726
TI  - Women who fall by the roadside: gender, sexual risk and alcohol in rural Uganda.
AB  - AIMS: To investigate community perceptions about the different relationship
      between alcohol consumption and sexual risk-taking for men and women in a high
      HIV prevalence African setting. DESIGN AND SETTING: Participatory learning and
      action (PLA) activities were conducted in five rural villages in south-western
      Uganda in 2002. For each village, discussions and visualization activities over
      the course of 5 days explored local concepts of fun, drinking alcohol and HIV
      related behavioural risks. Twelve focus group discussions (FGDs) investigated
      emerging themes. Analysis is based on visual outputs, observation notes and focus
      group transcripts. PARTICIPANTS: Attendance at sex-segregated PLA sessions was
      open to all village residents. FGDs were purposively sampled from drinkers and
      general population groups. FINDINGS: For men, drinking is conducted invariably
      outside the home, usually at night in bars, emphasizing independence, masculinity
      and freedom from domestic responsibilities. For women, drinking outside male
      supervision challenges feminine ideals of domesticity and signifies potential
      sexual vulnerability. Accepting drinks from men was viewed as signifying assent
      to sex and refusal could justify men resorting to sexual coercion. Even though
      drinking is seen to promote sexual risk, HIV prevention campaigns were considered
      unwelcome in bars. Communities preferred seminars involving drinkers and non
      drinkers alike. CONCLUSIONS: Public drinking in this community serves as a marker
      for men willing to exercise privileges of independence (sexual and otherwise) and
      women willing to defy gender norms (and risk the sexual consequences). The social
      and symbolic context of drinking suggests why effective HIV prevention around
      alcohol should not be limited to drinking environments alone.

PMID- 16911727
TI  - Alcohol consumption and out-patient services utilization by abstainers and
      drinkers.
AB  - AIMS: Previous studies have found that abstainers utilize out-patient health
      services more than alcohol consumers. The aim of this study was to investigate
      this relationship further by including several confounding variables and effect
      modifiers. It was hypothesized that abstainers utilize more health services
      because they have less social resources, practice more risky health behaviours,
      have poorer self-reported health and suffer more from chronic diseases. DESIGN
      AND PARTICIPANTS: Cross-sectional health survey of a random sample of adults aged
      20-64 in Pomerania, Germany. The response rate was 68.8%. Alcohol consumption was
      assessed using a quantity-frequency measure and categorized into past-year
      abstainers, low-risk, medium-risk and high-risk drinkers. Confounders and effect
      modifiers included socio-demographic and health-related variables. FINDINGS:
      Abstainers had a 43% higher rate (rate ratio = 1.43, 95% CI = 1.24, 1.63) of
      physician visits compared to low-risk drinkers, adjusting for age and gender.
      Medium-risk and high-risk drinkers did not differ from low-risk drinkers in terms
      of out-patient visits. Further regression adjustment for socio-economic
      covariates, self-reported health status and chronic diseases suggested that
      abstainers used more out-patient services because they were more ill than
      drinkers. The effect of mental health status and the number of chronic diseases
      on out-patient visits was greater for abstainers than drinkers. CONCLUSIONS: The
      relation between alcohol consumption and out-patient services is explained partly
      by poorer health among the abstainers. Further research is needed to affirm these
      results, such as transferring this evidence to the utilization of in-patient
      health services.

PMID- 16911728
TI  - Concurrent use and order of use of cocaine and alcohol: behavioural differences
      between users of crack cocaine and cocaine powder.
AB  - AIMS: The study investigates patterns of cocaine use and alcohol use when these
      substances were taken on their own, the order of administration of alcohol and of
      cocaine when the two substances were taken together, and changes in the doses of
      alcohol and of cocaine when the two substances were taken together. The study
      further investigates differences in the combined use of the two substances by
      users of cocaine powder and crack cocaine. DESIGN: Entry criteria for the study
      were current (previous 30 days) use of both alcohol and cocaine. Study
      participants (n = 102) were recruited from clinical and non-clinical settings.
      Data were collected by face-to-face structured interviews. FINDINGS: Different
      patterns of combined cocaine and alcohol use were reported by cocaine powder and
      crack cocaine users. Cocaine powder users tended to take increased doses of both
      cocaine and alcohol when these were used in combination. During high-dose crack
      using episodes, crack users tended to drink lower amounts of alcohol than usual.
      Cocaine powder users tended to use cocaine and alcohol concurrently. Crack users
      tended to use alcohol at the end of crack-using sessions. CONCLUSIONS: The
      observed differences are not understood clearly but may be influenced by
      differential effects of route of administration upon absorption, bioavailability
      and the balance of euphoric/dysphoric effects. Research studies of the combined
      use of cocaine and alcohol should distinguish explicitly between the use of
      cocaine by different routes of administration, and this should be specified in
      the description of subject samples.

PMID- 16911729
TI  - Systemic disease among cases of fatal opioid toxicity.
AB  - AIMS: To determine levels of systemic disease among cases of death due to opioid
      toxicity. DESIGN: Analysis of coronial cases. SETTING: Sydney, Australia. CASES:
      A total of 841 cases of death due to opioid toxicity (1 January 1998-31 December
      2002). FINDINGS: Ventricular hypertrophy was present in 5.9% of cases and severe
      coronary artery atherosclerosis in 5.7%. Severe coronary pathology was more
      pronounced among older cases. Pre-existing bronchopneumonia was present in 13.2%
      of cases. Hepatic pathology was the most common type of pathology, and was far
      more marked among older cases. Cirrhosis was present in 25.3% of those aged > 44
      years. Levels of renal pathology were comparatively low, but were related
      significantly to increasing age. Systemic disease in more than one organ system
      was present in 24.4% of cases, and was related to increasing age (44% of those
      aged > 44 years). The only pathology for which gender was an independent
      predictor among opioid cases was ventricular hypertrophy, more common in males.
      CONCLUSIONS: Systemic disease, most prominently liver disease, is common among
      fatal opioid toxicity cases, and may be a factor in understanding the dynamics
      and age demographics of opioid-related death.

PMID- 16911730
TI  - Attentional bias predicts heroin relapse following treatment.
AB  - AIMS: Previous studies have shown that abstinent heroin addicts exhibit an
      attentional bias to heroin-related stimuli. It has been suggested that
      attentional bias may represent a vulnerability to relapse into drug use. In the
      present study, the predictive value of pre-treatment attentional bias on relapse
      was examined in a population of abstinent heroin addicts. Further, the effect of
      cue exposure therapy (CET) on attentional bias was studied. DESIGN: Participants
      were assigned randomly to receive nine sessions of CET or placebo psychotherapy.
      SETTING: An in-patient drug abuse treatment setting. PARTICIPANTS: Abstinent
      heroin-dependent patients. MEASUREMENTS: Participants completed the emotional
      Stroop task both before and after completing treatment. FINDINGS: Pre-treatment
      attentional bias predicted relapse at 3-month follow-up, even when controlling
      for self-reported cravings at the test session. Further, attentional bias was
      reduced in both groups after therapy, independent of treatment condition.
      CONCLUSIONS: Attentional bias may tap an important component of drug dependence
      as it is a predictor of opiate relapse. However, CET does not specifically reduce
      attentional bias.

PMID- 16911731
TI  - Prenatal marijuana exposure contributes to the prediction of marijuana use at age
      14.
AB  - AIM: To evaluate the effects of prenatal marijuana exposure (PME) on the age of
      onset and frequency of marijuana use while controlling for identified confounds
      of early marijuana use among 14-year-olds. DESIGN: In this longitudinal cohort
      study, women were recruited in their fourth prenatal month. Women and children
      were followed throughout pregnancy and at multiple time-points into adolescence.
      SETTING AND PARTICIPANTS: Recruitment was from a hospital-based prenatal clinic.
      The women ranged in age from 18 to 42, half were African American and half
      Caucasian, and most were of lower socio-economic status. The women were generally
      light to moderate substance users during pregnancy and subsequently. At 14 years,
      580 of the 763 offspring-mother pairs (76%) were assessed. A total of 563 pairs
      (74%) was included in this analysis. MEASUREMENTS: Socio-demographic,
      environmental, psychological, behavioral, biological and developmental factors
      were assessed. Outcomes were age of onset and frequency of marijuana use at age
      14. PME predicted age of onset and frequency of marijuana use among the 14-year
      old offspring. This finding was significant after controlling for other variables
      including the child's current alcohol and tobacco use, pubertal stage, sexual
      activity, delinquency, peer drug use, family history of drug abuse and
      characteristics of the home environment including parental depression, current
      drug use and strictness/supervision. CONCLUSIONS: Prenatal exposure to marijuana,
      in addition to other factors, is a significant predictor of marijuana use at age
      14.

PMID- 16911732
TI  - Acute effects of cocaine in two models of inhibitory control: implications of non
      linear dose effects.
AB  - AIMS: This study examined dose-response effects of oral cocaine on the inhibitory
      control of behavior in adult cocaine users using two different behavioral models
      of inhibitory control. DESIGN: Adults (n = 12) with a history of cocaine use
      performed the stop-signal and cue-dependent go-no-go task to measure inhibitory
      control of behavior in response to a range of oral cocaine HCl doses (0, 100, 200
      and 300 mg). FINDINGS: Although both tasks showed cocaine-induced facilitation of
      inhibitory control, dose-response functions differed depending on the measures.
      The stop-signal measure revealed a quadratic dose-response function and the cued
      go-no-go measure showed a more orderly, linear improvement as a function of dose.
      CONCLUSIONS: The evidence suggests a two-phasic dose-response in which
      facilitating effects of stimulant drugs on inhibitory control might be limited to
      a range of intermediate doses, above which improvement is no longer evident and
      impairing effects could possibly emerge.

PMID- 16911733
TI  - Methadone-associated Torsades de Pointes (polymorphic ventricular tachycardia) in
      opioid-dependent patients.
AB  - AIMS: We reviewed all the publications concerning methadone-associated Torsades
      de Pointes (TdP) (polymorphic ventricular tachycardia) in opioid-dependent
      patients in order to characterize the clinical circumstances leading to this
      serious complication. METHODS: Our literature search yielded 14 reports on 40
      patients with methadone-associated TdP. We gathered and recorded the risk factors
      for TdP mentioned in those reports, among other clinical aspects. RESULTS: The
      most prevalent risk factors for TdP were high-dose methadone (n = 39, 97.5%) and
      concomitant use of agents that increase serum methadone levels or trigger TdP (n
      = 22, 55%). HIV infection (n = 16), hypokalaemia (n = 14), female sex (n = 13),
      liver cirrhosis or renal failure (n = 11) and heart disease (n = 9) were also
      described. All the patients had at least one and 34 (85%) had two or more risk
      factors for TdP during methadone treatment. CONCLUSIONS: We wish to raise the
      level of awareness of risk factors for TdP among physicians in heroin-treatment
      clinics who frequently prescribe methadone.

PMID- 16911734
TI  - Widespread axonal damage in the brain of drug abusers as evidenced by
      accumulation of beta-amyloid precursor protein (beta-APP): an immunohistochemical
      investigation.
AB  - BACKGROUND: In drug abusers, white matter changes have been described by
      neuroimaging analyses in different brain regions. A specific pattern of
      involvement or a predominance of a specific brain region could not be drawn.
      AIMS: To examine alterations of the white matter as a possible morphological
      substrate of the neuroimaging findings. METHODS: Brain specimens of 30 polydrug
      abusers and 20 controls were obtained at autopsy. The white matter from 11
      different brain regions was analysed by means of immunohistochemistry for beta
      amyloid precursor protein (beta-APP), a marker of axonal damage. FINDINGS: In the
      white matter of polydrug abusers, beta-APP-immunopositive accumulations were
      increased significantly compared to controls. They were more prominent in the
      brains of younger drug abusers than in those of the elderly. With the exception
      of five cases (four polydrug abusers and one control case), there were no
      significant white matter changes seen on myelin-stained sections, but there was a
      concomitant microglial activation. CONCLUSIONS: Our results show a significant
      axonal damage in the brains of polydrug abusers, which might represent the
      morphological substrate of a chronic-progressive drug-induced toxic-metabolic
      process. It is yet to be established if the observed changes are responsible for
      the alterations seen in different neuroimaging analyses and which drugs of abuse
      might be of major pathogenetic significance.

PMID- 16911735
TI  - Puffy hand syndrome due to drug addiction: a case-control study of the
      pathogenesis.
AB  - AIM: We studied the pathogenesis of puffy hand syndrome of intravenous drug use.
      We hypothesized that injections of high-dose sublingual buprenorphine, instead of
      the recommended sublingual administration, could play an important role in
      lymphatic obstruction and destruction. DESIGN AND PARTICIPANTS: We set up a case
      control study in substitution centres, recruiting intravenous drug addicts with
      and without puffy hands, respectively. The subjects were asked to answer
      anonymously a questionnaire of 40 items comprising social and demographic status,
      history of illicit drugs use, buprenorphine misuse and injection practices.
      FINDINGS: We included 33 cases and 33 controls, mean age of 34 years. They were
      past heroin users, mainly methadone-substituted. In multivariate analysis, sex
      (women) (OR = 8.9, P = 0.03), injections in the hands (OR = 5.9, P = 0.03),
      injections in the feet (OR = 6.5, P = 0.01) and the absence of tourniquet (OR =
      7.0, p = 0.02) were significant risk factors for puffy hand syndrome. In 69.7% of
      the cases and 59.4% of the controls, respectively, there was a high-dose
      sublingual buprenorphine misuse, although it appeared not to be a significant
      risk factor for puffy hand syndrome. CONCLUSIONS: Injection practices are likely
      to cause puffy hands syndrome, but buprenorphine misuse should not be considered
      as a significant risk factor. However, intravenous drug users must still be
      warned of local and systemic complications of intravenous drug misuse.

PMID- 16911736
TI  - The ATTEMPT cohort: a multi-national longitudinal study of predictors, patterns
      and consequences of smoking cessation; introduction and evaluation of internet
      recruitment and data collection methods.
AB  - AIMS: The ATTEMPT study was designed to chart the natural history of smoking
      cessation and associated short-term health outcomes and effects on medical
      resource utilization among a cohort recruited across multiple countries. This
      paper describes the methods for recruitment and follow-up, the baseline
      population characteristics of the enrolled population and 1-year response rates.
      DESIGN: ATTEMPT is a multi-national prospective cohort study that used the
      internet for subject recruitment and online assessments every 3 months for 2.5
      years. SETTING: Subjects were recruited via e-mail from existing internet panels
      [Canada (n = 208), France (n = 201), the United Kingdom (n = 200) and the United
      States (n = 1400]. SUBJECTS: Panel members who were aged 35-65 years, smoked at
      least five cigarettes per day and at initiation stated an intention to quit
      smoking within the next 3 months were eligible for this study. MEASUREMENTS:
      Measures included: attempts to quit, smoking status, smoking history, nicotine
      dependence and craving, methods used to quit smoking, reasons for quitting or
      failing to quit smoking, short-term health effects, health resource utilization,
      wellbeing, concern over weight gain, confidence in preventing weight gain, body
      weight and demographics. In addition, in-home assessments of weight were
      undertaken by field staff for a random sample of US participants. FINDINGS:
      Country-specific recruitment was completed within 17 days. The recruitment method
      produced a sample with characteristics broadly similar to those found in national
      surveys of smokers except for higher prevalence of obesity in the US and Canadian
      samples and higher educational level. At the end of 1 year the response rate was
      52%, and there was little evidence of differential loss to follow-up by key
      subject characteristics. Weight reported in the survey was found to correlate
      highly with weight measured during in-home visits. CONCLUSION: This paper
      demonstrates the feasibility of enrolling and following a diverse cohort of
      smokers for self-reported health and behaviour measures via the internet.

PMID- 16911737
TI  - Mechanism of action of a decision aid for smoking cessation treatment.

PMID- 16911746
TI  - The hypothalamic-pituitary-adrenal axis: a target for intervention in early
      psychosis?

PMID- 16911747
TI  - Stress, the hippocampus and the hypothalamic-pituitary-adrenal axis: implications
      for the development of psychotic disorders.
AB  - OBJECTIVE: The experience of stress is commonly implicated in models of the onset
      of psychotic disorders. However, prospective studies investigating associations
      between biological markers of stress and the emergence of psychotic disorders are
      limited and inconclusive. One biological system proposed as the link between the
      psychological experience of stress and the development of psychosis is the
      Hypothalamic-Pituitary-Adrenal (HPA) axis. This paper summarizes and discusses
      evidence supporting a role for HPA-axis dysfunction in the early phase of
      schizophrenia and related disorders. METHOD: A selective review of psychiatric
      and psychological research on stress, coping, HPA-axis, the hippocampus and
      psychotic disorders was performed, with a particular focus on the relationship
      between HPA-axis dysfunction and the onset of psychotic disorders. RESULTS:
      Individual strands of past research have suggested that the HPA-axis is
      dysfunctional in at least some individuals with established psychotic disorders;
      that the hippocampus is an area of the brain that appears to be implicated in the
      onset and maintenance of psychotic disorders; and that an increase in the
      experience of stress precedes the onset of a psychotic episode in some
      individuals. Models of the onset and maintenance of psychotic disorders that link
      these individual strands of research and strategies for examining these models
      are proposed in this paper. CONCLUSIONS: The current literature provides some
      evidence that the onset of psychotic disorders may be associated with a higher
      rate of stress and changes to the hippocampus. It is suggested that future
      research should investigate whether a relationship exists between psychological
      stress, HPA-axis functioning and the hippocampus in the onset of these disorders.
      Longitudinal assessment of these factors in young people at 'ultra' high risk of
      psychosis and first-episode psychosis cohorts may enhance understanding of the
      possible interaction between them in the early phases of illness.

PMID- 16911748
TI  - Neuropsychiatry of complex visual hallucinations.
AB  - OBJECTIVE: To describe the phenomenology and pathophysiology of complex visual
      hallucinations (CVH) in various organic states, in particular Charles Bonnet
      syndrome and peduncular hallucinosis. METHOD: Three cases of CVH in the setting
      of pontine infarction, thalamic infarction and temporoparietal epileptiform
      activity are presented and the available psychiatric, neurological and biological
      literature on the structures of the central nervous system involved in producing
      hallucinatory states is reviewed. RESULTS: Complex visual hallucinations can
      arise from a variety of processes involving the retinogeniculocalcarine tract, or
      ascending brainstem modulatory structures. The cortical activity responsible for
      hallucinations results from altered or reduced input into these regions, or a
      loss of ascending inhibition of their afferent pathways. CONCLUSIONS: A
      significant degree of overlaps exists between the concepts of Charles Bonnet
      syndrome and peduncular hallucinosis. The fluidity of these eponymous syndromes
      reduces their validity and meaning, and may result in an inappropriate
      attribution of the underlying pathology. An understanding of how differing
      pathologies may produce CVH allows for the appropriate tailoring of treatment,
      depending on the site and nature of the lesion and content of perceptual
      disturbance.

PMID- 16911749
TI  - Cortical-subcortical re-entrant circuits and recurrent behaviour.
AB  - OBJECTIVE: To explore the application of Parallel Distributed Processing (PDP)
      models to biological cortical-subcortical re-entrant circuits, and their
      implications for recurrent psychiatric symptomatology. METHOD: The literature on
      cortical-cortical and cortical-subcortical re-entrant circuits is reviewed and
      possible neural network (PDP) analogies are described. Examples from the
      attention deficit hyperactivity disorder (ADHD) and obsessive-compulsive disorder
      (OCD) literature are explored and compared. RESULTS: A common circuit
      architecture for at least five circuits was found. Recurrent PDP models suggest
      that subcortical centres can exert significant influences on behaviour, but their
      effect will depend on gating processes at higher centres, governed by both
      feedback (phasic arousal/reinforcement) and synaptic activity at higher levels.
      The latter can vary around a 'Golden Mean' at cortical receptor levels, which
      degrades when it is either over-aroused or under-aroused. The Continuous
      Performance Task, which models both working memory and inhibitory processing is a
      useful task for functional imaging of an attentional network. CONCLUSION:
      Recurrent symptoms occur as a result of incoordination between phasic subcortical
      inputs and synaptic gating processes in cortical-subcortical circuits. Obsessive
      compulsive disorder and ADHD represent opposite manifestations of recurrent
      cortical-subcortical processing deficits, with excess arousal in the former and
      insufficient maintenance of reinforcement and working memory in the latter. These
      processes may be subject to separate genetic influences at cortical versus
      subcortical levels.

PMID- 16911750
TI  - Daily and spaced treatment with transcranial magnetic stimulation in major
      depression: a pilot study.
AB  - OBJECTIVE: Transcranial magnetic stimulation is an emerging treatment of
      treatment-resistant depression. Current protocols rely on daily treatments. This
      study was designed to determine whether the time period over which treatment is
      delivered is an important factor in efficacy. METHOD: Sixteen adult patients with
      treatment-resistant major depression were randomly assigned to one of the two
      treatment groups, both of which received 2 weeks of treatment. One group received
      daily treatment (10 treatments, on business days). The other group received three
      treatments in week one, and two treatments in week two (five treatments, on
      spaced business days). Mood was rated using the Hamilton Depression Rating Scale
      (HDRS) and a self-rated visual analogue scale. Response was defined as a 50%
      reduction in HDRS rating, and remission was defined as achieving an HDRS score of
      8 or less. The groups were compared throughout the 2-week study period. RESULTS:
      At entry, there were no demographic differences between the groups. Multivariate
      tests showed a significant main effect for time (Pillai trace=0.76, F(4,56)=8.56,
      p<0.001, power=0.99) reflecting the improvement in both measures of depression
      during treatment. There was no significant difference between the groups overall
      (Pillai trace=0.25, F(2,13)=2.12, p=0.16, power=0.36). Additionally, there was no
      significant interaction between time and treatment group (Pillai trace=0.18,
      F(4,56)=1.35, p=0.26, power=0.39) indicating that the significant improvement in
      depression over time was similar for both treatment groups. There were no
      significant differences in response and remission rates between the groups.
      CONCLUSION: The time period of treatment appeared to be an important outcome
      factor. This suggests that less than daily transcranial magnetic stimulation
      treatment may be a useful clinical alternative.

PMID- 16911751
TI  - Naturalistic study of the use of transcranial magnetic stimulation in the
      treatment of depressive relapse.
AB  - BACKGROUND: The efficacy of repetitive transcranial magnetic stimulation (rTMS)
      in the treatment of depression has been assessed in a number of acute treatment
      trials during the last 10 years. Little is known about the long-term impact of
      the treatment on the disorder and its effectiveness when applied for repeated
      relapses of depression over time. METHOD: Nineteen patients who had previously
      responded to rTMS in clinical trials received treatment with rTMS for a total of
      30 episodes of depressive relapse. RESULTS: Approximately 10 months elapsed
      between treatment episodes. The majority of patients achieved a significant
      improvement in each treatment course with significant improvements achieved in
      patients treated with both low-frequency right-sided rTMS and high-frequency left
      sided rTMS. CONCLUSIONS: The study suggests that rTMS may have value in the
      treatment of episodes of depressive relapse with little reduction in efficacy
      over time.

PMID- 16911752
TI  - Help-seeking by rural residents for mental health problems: the importance of
      agrarian values.
AB  - OBJECTIVE: To examine the role of stoicism, self-efficacy and perceived stigma in
      predicting help-seeking by rural residents, for mental health problems. METHOD: A
      cross-sectional community survey was conducted with a sample of 467 rural
      residents (58% female), who completed self-report questionnaires assessing
      current levels of symptomatology, disability, perceived stigma, self-efficacy,
      stoicism, attitudes towards and experience of seeking help for psychological
      problems. RESULTS: Overall, 27.6% (n=129) of respondents had sought help from a
      general practitioner and/or mental halth professional for psychological problems
      or a mental health issue. More women than men reported having sought such help.
      Lifetime help-seeking for a psychological problem or mental health issue was
      positively associated with higher levels of distress and lower levels of stoicism
      and, to a lesser extent, lower levels of self-efficacy. CONCLUSIONS: Efforts to
      improve help-seeking by rural residents for mental health problems should focus
      on understanding and addressing attitudes, such as stoicism which act as barriers
      to help-seeking.

PMID- 16911753
TI  - Web-based survey of depression, anxiety and stress in first-year tertiary
      education students in Hong Kong.
AB  - OBJECTIVE: The mental health of tertiary education students is an area of
      increasing concern worldwide. The objective of this study is to examine the
      prevalence of depression, anxiety and stress in first-year tertiary education
      students in Hong Kong. METHOD: Depression, anxiety and stress were measured by
      the 42-item Depression Anxiety Stress Scales, completed on the web by
      participating students anonymously. RESULTS: A total of 7915 students completed
      the survey, yielding a response rate of 27.5%. Depression, anxiety and stress
      levels of moderate severity or above were found in 21%, 41% and 27% of our
      respondents, respectively. CONCLUSIONS: The web-based survey methodology was well
      accepted by our sample group of tertiary education students. We found high rates
      of psychological morbidity in first-year tertiary education students in Hong
      Kong. The high prevalence of depression, anxiety and stress symptoms in the first
      year of college life is alarming. It illustrates the need for primary and
      secondary prevention measures, with development of adequate and appropriate
      support services for this group.

PMID- 16911754
TI  - Mental health literacy in rural Queensland: results of a community survey.
AB  - OBJECTIVES: The aim of this study was to assess the awareness of, and attitudes
      to, mental health issues in rural dwelling Queensland residents. A secondary
      objective was to provide baseline data of mental health literacy prior to the
      implementation of Australian Integrated Mental Health Initiative--a health
      promotion strategy aimed at improving the health outcomes of people with chronic
      or recurring mental disorders. METHOD: In 2004 a random sample of 2% (2132) of
      the estimated adult population in each of eight towns in rural Queensland was
      sent a postal survey and invited to participate in the project. A series of
      questions were asked based on a vignette describing a person suffering major
      depression. In addition, questions assessed respondents' awareness and
      perceptions of community mental health agencies. RESULTS: Approximately one-third
      (36%) of those surveyed completed and returned the questionnaire. While a higher
      proportion of respondents (81%) correctly identified and labelled the problem in
      the vignette as depression than previously reported in Australian community
      surveys, the majority of respondents (66%) underestimated the prevalence of
      mental health problems in the community. Furthermore, a substantial number of
      respondents (37%) were unaware of agencies in their community to assist people
      with mental health issues while a majority of respondents (57.6%) considered that
      the services offered by those agencies were poor. CONCLUSION: While mental health
      literacy in rural Queensland appears to be comparable to other Australian
      regions, several gaps in knowledge were identified. This is in spite of recent
      widespread coverage of depression in the media and thus, there is a continuing
      need for mental health education in rural Queensland.

PMID- 16911755
TI  - Influence of gender on mental health literacy in young Australians.
AB  - OBJECTIVES: To determine the effects of gender on mental health literacy in young
      people between 12 and 25 years of age. DESIGN: Computer-Assisted Telephone
      Interviewing was employed to conduct a cross-sectional structured interview
      focusing on young people's awareness of depression and psychosis. PARTICIPANTS:
      The sample comprised 1207 young Australians (539 males and 668 females) between
      the ages of 12-25 recruited from two metropolitan and two regional areas within
      Victoria. Six hundred and six respondents were presented a depression vignette
      and 601 were presented a psychosis vignette. RESULTS: Female respondents (60.7%)
      were significantly more likely to correctly identify depression in the vignette
      as compared to male respondents (34.5%). No significant gender differences were
      noted for the psychosis vignette. Males were less significantly likely to endorse
      seeing a doctor or psychologist/counsellor for the treatment of psychosis. Males
      were also significantly more likely than females to endorse alcohol as a way of
      dealing with depression and antibiotics as useful for dealing with psychosis.
      CONCLUSION: Gender differences in mental health literacy are striking. Males
      showed significantly lower recognition of symptoms associated with mental illness
      and were more likely endorse the use alcohol to deal with mental health problems.
      Such factors may contribute to the delays in help seeking seen in young males.
      Further research is needed to delineate how these gender differences in young
      people may obstruct help seeking, early intervention and other aspects of mental
      health service delivery.

PMID- 16911756
TI  - Measuring physical and mental health using the SF-12: implications for community
      surveys of mental health.
AB  - OBJECTIVE: The effects of using different approaches to scoring the SF-12 summary
      scales of physical and mental health were examined with a view to informing the
      design and interpretation of community-based survey research. METHOD: Data from a
      population-based study of 7485 participants in three cohorts aged 20-24, 40-44
      and 60-64 years were used to examine relationships among measures of physical and
      mental health calculated from the same items using the SF-12 and RAND-12
      approaches to scoring, and other measures of chronic physical conditions and
      psychological distress. RESULTS: A measure of physical health constructed using
      the RAND-12 scoring showed a monotonic negative association with psychological
      distress as measured by the Goldberg depression and anxiety scales. However, a
      non-monotonic association was evident in the relationship between SF-12 physical
      health scores and distress, with very high SF-12 physical health scores
      corresponding with high levels of distress. These relationships highlight
      difficulties in interpretation that can arise when using the SF-12 summary scales
      in some analytical contexts. CONCLUSIONS: It is recommended that community
      surveys that measure physical and mental functioning using the SF-12 items
      generate summary scores using the RAND-12 protocol in addition to the SF-12
      approach. In general, researchers should be wary of using factor scores based on
      orthogonal rotation, which assumes that measures are uncorrelated, to represent
      constructs that have an actual association.

PMID- 16911757
TI  - Mentally abnormal homicide in New Zealand as defined by legal and clinical
      criteria: a national study.
AB  - BACKGROUND: Homicides by people with mental illness have been studied using
      either clinical or legal categorization of the homicide as abnormal. No previous
      study has employed both definitions in the same population. METHOD: A
      retrospective study of all homicides in New Zealand between 1988 and 2000
      considered mentally abnormal homicide using a legal definition (when the courts
      deemed a contribution of mental illness was present) and a clinical definition
      (defined as the presence of a discharge diagnosis from inpatient mental health
      treatment) of 'mentally abnormal'. Rates, characteristics and time trends were
      investigated. RESULTS: Of the 844 cases, 7.1% met legal criteria for being
      mentally abnormal, while 7.7% had ever received a diagnosis for a psychotic
      illness, and a further 14.5% had been admitted to a psychiatric hospital for any
      other reason. The majority (60%) of perpetrators with a psychotic diagnosis
      received a mental health disposition from the court. Of these, 60% were first
      diagnosed with their psychotic illness prior to the homicide, while 28% were
      first diagnosed at the time of the offence and a further 12% after imprisonment.
      Of all those who received a psychotic diagnosis, 89% had post-conviction
      admissions or a mental health disposition. CONCLUSION: Legal and clinical
      definitions of mentally abnormal homicide detect similar rates of mentally
      abnormal homicide, but illustrate somewhat different dimensions of the
      relationship between mental illness and homicide.

PMID- 16911758
TI  - Energy expenditure and physical activity in clozapine use: implications for
      weight management.
AB  - OBJECTIVE: The management of atypical antipsychotic-induced weight gain is a
      significant challenge for people with mental illness. Fundamental research into
      energy metabolism in people taking atypical antipsychotic medication has been
      neglected. The current study of men with schizophrenia taking clozapine aimed to
      measure total energy expenditure (TEE) and energy expended on physical activity-
      activity energy expenditure (AEE) and to consider the clinical implications of
      the findings. METHOD: The well-established reference method of doubly labelled
      water (DLW) was used to measure TEE and AEE in men with schizophrenia who had
      been taking clozapine for more than 6 months. Resting energy expenditure was
      determined using indirect calorimetry. RESULTS: The TEE was 2511+/-606 kcal day-1
      which was significantly different to World Health Organization recommendations
      (more than 20% lower). The Physical activity level (PAL) was 1.39+/-0.27
      confirming the sedentary nature of people with schizophrenia who take clozapine.
      CONCLUSIONS: The findings support the need for weight management strategies for
      people with schizophrenia who take clozapine to focus on the enhancement of
      energy expenditure by increasing physical activity and reducing inactivity or
      sedentary behaviours, rather than relying primarily on strategies to reduce
      energy intake.

PMID- 16911759
TI  - Polydipsia with normal natremia induced by Valproic Acid.

PMID- 16911760
TI  - Response to 'blood borne viral and sexually transmissible infections among
      psychiatric populations: what are we doing about them?'.

PMID- 16911761
TI  - Response to 'a non-linear theory of schizophrenia'.

PMID- 16911763
TI  - Response to 'mindfulness-based psychotherapies' (2).

PMID- 16911764
TI  - Response to 'mindfulness-based psychotherapies' (1).

PMID- 16911767
TI  - A role for adrenomedullin in the pathogenesis of alveolar edema.

PMID- 16911768
TI  - Is there an association between anti-TNF monoclonal antibody therapy in
      rheumatoid arthritis and risk of malignancy and serious infection? Commentary on
      the meta-analysis by Bongartz et al.
AB  - A recent meta-analysis of randomized clinical trials reported by Bongartz and
      coworkers raised concerns about an increased rate of malignancy and serious
      infection in rheumatoid arthritis patients treated with anti-tumour necrosis
      factor monoclonal antibodies. This commentary discusses some of the
      methodological issues in their analysis and urges caution in interpreting the
      results.

PMID- 16911770
TI  - Risk adjustment for inter-hospital comparison of primary cesarean section rates:
      need, validity and parsimony.
AB  - BACKGROUND: Cesarean section rates is often used as an indicator of quality of
      care in maternity hospitals. The assumption is that lower rates reflect in
      developed countries more appropriate clinical practice and general better
      performances. Hospitals are thus often ranked on the basis of caesarean section
      rates. The aim of this study is to assess whether the adjustment for clinical and
      sociodemographic variables of the mother and the fetus is necessary for inter
      hospital comparisons of cesarean section (c-section) rates and to assess whether
      a risk adjustment model based on a limited number of variables could be
      identified and used. METHODS: Discharge abstracts of labouring women without
      prior cesarean were linked with abstracts of newborns discharged from 29
      hospitals of the Emilia-Romagna Region (Italy) from 2003 to 2004. Adjusted ORs of
      cesarean by hospital were estimated by using two logistic regression models: 1) a
      full model including the potential confounders selected by a backward procedure;
      2) a parsimonious model including only actual confounders identified by the
      "change-in-estimate" procedure. Hospital rankings, based on ORs were examined.
      RESULTS: 24 risk factors for c-section were included in the full model and 7
      (marital status, maternal age, infant weight, fetopelvic disproportion, eclampsia
      or pre-eclampsia, placenta previa/abruptio placentae,
      malposition/malpresentation) in the parsimonious model. Hospital ranking using
      the adjusted ORs from both models was different from that obtained using the
      crude ORs. The correlation between the rankings of the two models was 0.92. The
      crude ORs were smaller than ORs adjusted by both models, with the parsimonious
      ones producing more precise estimates. CONCLUSION: Risk adjustment is necessary
      to compare hospital c-section rates, it shows differences in rankings and
      highlights inappropriateness of some hospitals. By adjusting for only actual
      confounders valid and more precise estimates could be obtained.

PMID- 16911769
TI  - Preventing autoimmune arthritis using antigen-specific immature dendritic cells:
      a novel tolerogenic vaccine.
AB  - Conventional treatments for autoimmune diseases have relied heavily on
      nonspecific immune suppressants, which possess a variety of adverse effects
      without inhibiting the autoimmune process in a specific manner. In the present
      study we demonstrate the effectiveness of antigen-specific, maturation-resistant,
      tolerogenic dendritic cells (DC) in suppressing collagen-induced arthritis, a
      murine model of rheumatoid arthritis. Treatment of DC progenitors with the NF
      kappaB inhibiting agent LF 15-0195 (LF) resulted in a population of tolerogenic
      DC that are characterized by low expression of MHC class II, CD40, and CD86
      molecules, as well as by poor allostimulatory capacity in a mixed leukocyte
      reaction. Administering LF-treated DC pulsed with keyhole limpet hemocyanin
      antigen to naive mice resulted hyporesponsiveness specific for this antigen.
      Furthermore, administration of LF-treated DC to mice with collagen-induced
      arthritis resulted in an improved clinical score, in an inhibited antigen
      specific T-cell response, and in reduced antibody response to the collagen. The
      efficacy of LF-treated DC in preventing arthritis was substantiated by
      histological examination, which revealed a significant decrease in inflammatory
      cell infiltration in the joints. In conclusion, we demonstrate that in vitro
      generated antigen-specific immature DC may have important potential as a
      tolerogenic vaccine for the treatment of autoimmune arthritis.

PMID- 16911771
TI  - Emerging advantages and drawbacks of telephone surveying in public health
      research in Ireland and the U.K.
AB  - BACKGROUND: Telephone surveys have been used widely in public health research
      internationally and are being increasingly used in Ireland and the U.K. METHODS:
      This study compared three telephone surveys conducted on the island of Ireland
      from 2000 to 2004, examining study methodology, outcome measures and the per unit
      cost of each completed survey. We critically examined these population-based
      surveys which all explored health related attitudes and behaviours. RESULTS: Over
      the period from 2000 to 2005 the percentage of calls which succeeded in
      contacting an eligible member of the public fell, from 52.9% to 31.8%. There was
      a drop in response rates to the surveys (once contact was established) from 58.6%
      to 17.7%. Costs per completed interview rose from 4.48 euro to 15.65 euro.
      Respondents were prepared to spend 10-15 minutes being surveyed, but longer
      surveys yielded poorer completion rates. Respondents were willing to discuss
      issues of a sensitive nature. Interviews after 9 pm were less successful, with
      complaints about the lateness of the call. Randomisation from electronic
      residential telephone directory databases excluded all ex-directory numbers and
      thus was not as representative of the general population as number generation by
      the hundred-bank method. However the directory database was more efficient in
      excluding business and fax numbers. CONCLUSION: Researchers should take
      cognisance of under-representativeness of land-line telephone surveys, of the
      increasing difficulties in contacting the public and of mounting personnel costs.
      We conclude that telephone surveying now requires additional strategies such as a
      multimode approach, or incentivisation, to be a useful, cost-effective means of
      acquiring data on public health matters in Ireland and the U.K.

PMID- 16911772
TI  - Molecular epidemiology of C. diphtheriae strains during different phases of the
      diphtheria epidemic in Belarus.
AB  - BACKGROUND: The reemergence of epidemic diphtheria in Belarus in 1990s has
      provided us with important information on the biology of the disease and the
      diversity of the causative agent Corynebacterium diphtheriae. Molecular
      investigations were conducted with the aim to analyze the genetic variability of
      C diphtheriae during the post-epidemic period. METHODS: The biotype and
      toxigenicity status of 3513 C. diphtheriae strains isolated from all areas in
      Belarus during a declining period of diphtheria morbidity (1996-2005) was
      undertaken. Of these, 384 strains were isolated from diphtheria cases, 1968 from
      tonsillitis patients, 426 from contacts and 735 from healthy carriers. Four
      hundred and thirty two selected strains were ribotyped. RESULTS: The C
      diphtheriae gravis biotype, which was prevalent during 1996-2000, was "replaced"
      by the mitis biotype during 2001-2005. The distribution of toxigenic C.
      diphtheriae strains also decreased from 47.1% (1996) to 5.8% (2005). Changes in
      the distribution of the epidemic ribotypes Sankt-Peterburg and Rossija were also
      observed. During 2001-2005 the proportion of the Sankt-Peterburg ribotype
      decreased from 24.3% to 2.3%, in contrast to the Rossija ribotype, that increased
      from 25.1% to 49.1%. The circulation of other toxigenic ribotypes (Otchakov,
      Lyon, Bangladesh), which were prevalent during the period of high diphtheria
      incidence, also decreased. But at the same time, the proportion of non-toxigenic
      strains with the Cluj and Rossija ribotypes dramatically increased and accounted
      for 49.3% and 30.1%, respectively. CONCLUSION: The decrease in morbidity
      correlated with the dramatic decrease in the isolation of the gravis biotype and
      Sankt Peterburg ribotype, and the prevalence of the Rossija ribotype along with
      other rare ribotypes associated with non-toxigenic strains (Cluj and Rossija, in
      particular).

PMID- 16911773
TI  - Intermediate and high peri-operative cardiac enzyme release following isolated
      coronary artery bypass surgery are independently associated with higher one-year
      mortality.
AB  - BACKGROUND: The relationship between cardiac enzyme (CE) release following
      coronary artery bypass surgery (CABG) and medium term outcome is unclear. We
      sought to determine the relationship between post-operative CE release and one
      year survival following isolated CABG. METHODS: Over three years 3,024
      consecutive patients underwent isolated CABG. Patient characteristics were
      prospectively recorded in a cardiac surgical database. CE release, taken as the
      highest single measurement recorded in the first 24 hours post-op, was abstracted
      from an electronic archive. All cause mortality was taken from a national
      registry of deaths. RESULTS: Data were complete for 2,860 (94.6%) patients. CK-MB
      isoenzyme (reference range 5-24 U/l) was recorded in 2,568 (89.8%), total CK in
      292 (10.2%). CE release three or more times the upper limit of the reference
      range (ULR) were recorded in 498 (17.4%) patients, 163 (5.7%) patients had CE
      more than six times ULR. There were 122 deaths (4.3%). Cox proportional hazards
      analysis showed that CE release 3-6 times ULR (adjusted HR 2.1 [95% CI: 1.6 to
      2.6], p = 0.002) and CE release six or more times the ULR (adjusted HR 5.0 [95%
      CI: 4.5 to 5.4], p < 0.001) were independently associated with increased one-year
      mortality. CONCLUSION: Cardiac enzyme release following CABG is associated with
      increased one-year all-cause mortality. The definition of peri-operative
      myocardial infarction following CABG should include elevation of CK-MB three or
      more times the upper limit of normal.

PMID- 16911774
TI  - Adenoid basal lesions of the uterine cervix: evolving terminology and
      clinicopathological concepts.
AB  - The epithelial proliferations that are designated adenoid basal carcinoma (ABC)
      in the current classification from the World Health Organization represent <1% of
      all cervical malignancies. These lesions may be associated, and occasionally show
      morphologic transitions with, conventional cervical malignancies. The
      determination of the precise frequency with which these so-called ABCs show this
      association is hampered by the inherent selection bias in the reported cases.
      However, this frequency appears to be substantial (>15%). The biologic course of
      ABCs that are associated with separate malignancies is largely dependent on the
      clinicopathologic parameters of the associated malignancies. Morphologically pure
      lesions, in contrast, have largely been associated with favorable patient
      outcomes, as none of the 66 reported patients have experienced tumor recurrence,
      metastases or tumor-associated death, irrespective of the modality of treatment.
      Although the finding of genome integrated high-risk human papillomavirus (HPV)
      types and p53 alterations in adenoid basal lesions (ABL) argue in support of
      their neoplastic nature, we identified no lines evidence that suggest an inherent
      malignancy for morphologically pure lesions. The finding of morphologic
      transitions between ABLs and conventional malignancies and shared HPV types in
      these areas, suggest that ABLs have some malignant potential. However, the
      precise magnitude of this potential is not readily quantifiable and should not
      dictate the management of morphologically pure lesions that are entirely
      evaluable. ABLs continue to occupy a unique position in human oncology in which
      the term carcinoma (without an in-situ suffix) is applied to a tumor that has not
      been shown to recur, metastasize or cause death. We concur with a previous
      proposal that the term ABC should be discarded and replaced with Adenoid Basal
      Epithelioma (ABE). In our opinion, there is insufficient evidence at present time
      to expose patients with morphologically pure lesions to the ominous implications-
      social, psychological, medical, financial--of a "carcinoma" diagnosis.
      Morphologically impure lesions should not be designated ABC or ABE. Furthermore,
      given the uncertainties regarding the frequency with which ABE are associated
      with separate malignancies, we suggest that the ABE designation only be applied
      when the tumor in question is entirely evaluable e.g in a hysterectomy specimen
      or in an excisional biopsy with negative margins. Otherwise, the generic
      designation Adenoid Basal Tumor is preferable. This approach strikes an
      appropriate balance between the need to prevent over-treatment of pure lesions on
      one hand, and the need to ensure that the lesions are indeed pure on the other.

PMID- 16911776
TI  - Stratification of non-small cell lung cancer patients for therapy with epidermal
      growth factor receptor inhibitors: the EGFR fluorescence in situ hybridization
      assay.
AB  - DNA fluorescence in situ hybridization (FISH) technology is used to study
      chromosomal and genomic changes in fixed cell suspensions and tissue block
      preparations. The technique is based on specific hybridization of small labeled
      DNA fragments, the probes, to complementary sequences in a target DNA molecule.
      Demand for FISH assays in formalin-fixed, paraffin-embedded tissues has been
      increasing, mainly in conditions in which diagnosis is not achieved in cell
      smears or tissue imprints, such as solid tumors. Moreover, the development of
      molecular targeted therapies in oncology has expanded the applicability of tests
      to predict sensitivity or resistance to these agents. The efficient use of
      tyrosine kinase inhibitors (TKI) of the epidermal growth factor receptor (EGFR)
      as therapeutical agents in advanced non-small cell lung cancer (NSCLC) depends on
      identification of patients likely to show clinical benefit from these specific
      treatments. The EGFR gene copy number determined by FISH has been demonstrated as
      an effective predictor of outcome from NSCLC patients to EGFR TKIs; however there
      are pending challenges for standardization of laboratory procedures and
      definition of the scoring system. This methodology article focuses on the EGFR
      FISH assay. It details the scoring system used in the studies conducted at the
      University of Colorado Cancer Center in which a significant association was found
      between increased EGFR copy numbers and clinical outcome to TKIs, and proposes
      interpretative guidelines for molecular stratification of NSCLC patients for TKI
      therapy.

PMID- 16911775
TI  - Identification of the ancestral killer immunoglobulin-like receptor gene in
      primates.
AB  - BACKGROUND: Killer Immunoglobulin-like Receptors (KIR) are essential immuno
      surveillance molecules. They are expressed on natural killer and T cells, and
      interact with human leukocyte antigens. KIR genes are highly polymorphic and
      contribute vital variability to our immune system. Numerous KIR genes, belonging
      to five distinct lineages, have been identified in all primates examined thus far
      and shown to be rapidly evolving. Since few KIR remain orthologous between
      species, with only one of them, KIR2DL4, shown to be common to human, apes and
      monkeys, the evolution of the KIR gene family in primates remains unclear.
      RESULTS: Using comparative analyses, we have identified the ancestral KIR lineage
      (provisionally named KIR3DL0) in primates. We show KIR3DL0 to be highly conserved
      with the identification of orthologues in human (Homo sapiens), common chimpanzee
      (Pan troglodytes), gorilla (Gorilla gorilla), rhesus monkey (Macaca mulatta) and
      common marmoset (Callithrix jacchus). We predict KIR3DL0 to encode a functional
      molecule in all primates by demonstrating expression in human, chimpanzee and
      rhesus monkey. Using the rhesus monkey as a model, we further show the expression
      profile to be typical of KIR by quantitative measurement of KIR3DL0 from an
      enriched population of natural killer cells. CONCLUSION: One reason why KIR3DL0
      may have escaped discovery for so long is that, in human, it maps in between two
      related leukocyte immunoglobulin-like receptor clusters outside the known KIR
      gene cluster on Chromosome 19. Based on genomic, cDNA, expression and
      phylogenetic data, we report a novel lineage of immunoglobulin receptors
      belonging to the KIR family, which is highly conserved throughout 50 million
      years of primate evolution.

PMID- 16911777
TI  - Propagation velocity profile in a cross-section of a cardiac muscle bundle from
      PSpice simulation.
AB  - BACKGROUND: The effect of depth on propagation velocity within a bundle of
      cardiac muscle fibers is likely to be an important factor in the genesis of some
      heart arrhythmias. MODEL AND METHODS: The velocity profile of simulated action
      potentials propagated down a bundle of parallel cardiac muscle fibers was
      examined in a cross-section of the bundle using a PSpice model. The model (20 x
      10) consisted of 20 chains in parallel, each chain being 10 cells in length. All
      20 chains were stimulated simultaneously at the left end of the bundle using
      rectangular current pulses (0.25 nA, 0.25 ms duration) applied intracellularly.
      The simulated bundle was symmetrical at the top and bottom (including two
      grounds), and voltage markers were placed intracellularly only in cells 1, 5 and
      10 of each chain to limit the total number of traces to 60. All electrical
      parameters were standard values; the variables were (1) the number of
      longitudinal gap-junction (G-j) channels (0, 1, 10, 100), (2) the longitudinal
      resistance between the parallel chains (Rol2) (reflecting the closeness of the
      packing of the chains), and (3) the bundle termination resistance at the two ends
      of the bundle (RBT). The standard values for Rol2 and RBT were 200 KOmega.
      RESULTS: The velocity profile was bell-shaped when there was 0 or only 1 gj
      channel. With standard Rol2 and RBT values, the velocity at the surface of the
      bundle (theta1 and theta20) was more than double (2.15 x) that at the core of the
      bundle (theta10, theta11). This surface:core ratio of velocities was dependent on
      the values of Rol2 and RBT. When Rol2 was lowered 10-fold, theta1 increased
      slightly and theta2decreased slightly. When there were 100 gj-channels, the
      velocity profile was flat, i.e. the velocity at the core was about the same as
      that at the surface. Both velocities were more than 10-fold higher than in the
      absence of gj-channels. Varying Rol2 and RBT had almost no effect. When there
      were 10 gj-channels, the cross-sectional velocity profile was bullet-shaped, but
      with a low surface/core ratio, with standard Rol2 and RBT values. CONCLUSION:
      When there were no or few gj-channels (0 or 1), the profile was bell-shaped with
      the core velocity less than half that at the surface. In contrast, when there
      were many gj-channels (100), the profile was flat. Therefore, when some gj
      channels close under pathophysiological conditions, this marked velocity profile
      could contribute to the genesis of arrhythmias.

PMID- 16911778
TI  - The OnyCOE-t questionnaire: responsiveness and clinical meaningfulness of a
      patient-reported outcomes questionnaire for toenail onychomycosis.
AB  - BACKGROUND: This research was conducted to confirm the validity and reliability
      and to assess the responsiveness and clinical meaningfulness of the OnyCOE-t, a
      questionnaire specifically designed to measure patient-reported outcomes (PRO)
      associated with toenail onychomycosis. METHODS: 504 patients with toenail
      onychomycosis randomized to receive 12 weeks of terbinafine 250 mg/day with or
      without target toenail debridement in the IRON-CLAD trial completed the OnyCOE-t
      at baseline, weeks 6, 12, 24, and 48. The OnyCOE-t is composed of 6 multi-item
      scales and 1 single-item scale. These include a 7-item Toenail Symptom
      assessment, which comprises both Symptom Frequency and Symptom Bothersomeness
      scales; an 8-item Appearance Problems scale; a 7-item Physical Activities
      Problems scale; a 1-item Overall Problem scale; a 7-item Stigma scale; and a 3
      item Treatment Satisfaction scale. In total, 33 toenail onychomycosis-specific
      items are included in the OnyCOE-t. Clinical data, in particular the percent
      clearing of mycotic involvement in the target toenail, and OnyCOE-t responses
      were used to evaluate the questionnaire's reliability, validity, responsiveness,
      and the minimally clinical important difference (MCID). RESULTS: The OnyCOE-t was
      shown to be reliable and valid. Construct validity and known groups validity were
      acceptable. Internal consistency reliability of multi-item scales was
      demonstrated by Cronbach's alpha > .84. Responsiveness was good, with the
      Treatment Satisfaction, Symptom Frequency, Overall Problem, and Appearance
      Problem scales demonstrating the most responsiveness (Guyatt's statistic of 1.72,
      1.31, 1.13, and 1.11, respectively). MCID was evaluated for three different
      clinical measures, and indicated that approximately an 8.5-point change (on a 0
      to 100 scale) was clinically meaningful based on a 25% improvement in target nail
      clearing. CONCLUSION: The OnyCOE-t questionnaire is a unique, toenail-specific
      PRO questionnaire that can be used with confidence in future studies of toenail
      onychomycosis. MCID was evaluated for three different clinical measures, and
      indicated that approximately a 7-point change (on a 0 to 100 scale) was
      clinically meaningful based on a 12.5% improvement in target nail clearing.

PMID- 16911779
TI  - Wikis, blogs and podcasts: a new generation of Web-based tools for virtual
      collaborative clinical practice and education.
AB  - BACKGROUND: We have witnessed a rapid increase in the use of Web-based
      'collaborationware' in recent years. These Web 2.0 applications, particularly
      wikis, blogs and podcasts, have been increasingly adopted by many online health
      related professional and educational services. Because of their ease of use and
      rapidity of deployment, they offer the opportunity for powerful information
      sharing and ease of collaboration. Wikis are Web sites that can be edited by
      anyone who has access to them. The word 'blog' is a contraction of 'Web Log' - an
      online Web journal that can offer a resource rich multimedia environment.
      Podcasts are repositories of audio and video materials that can be "pushed" to
      subscribers, even without user intervention. These audio and video files can be
      downloaded to portable media players that can be taken anywhere, providing the
      potential for "anytime, anywhere" learning experiences (mobile learning).
      DISCUSSION: Wikis, blogs and podcasts are all relatively easy to use, which
      partly accounts for their proliferation. The fact that there are many free and
      Open Source versions of these tools may also be responsible for their explosive
      growth. Thus it would be relatively easy to implement any or all within a Health
      Professions' Educational Environment. Paradoxically, some of their disadvantages
      also relate to their openness and ease of use. With virtually anybody able to
      alter, edit or otherwise contribute to the collaborative Web pages, it can be
      problematic to gauge the reliability and accuracy of such resources. While
      arguably, the very process of collaboration leads to a Darwinian type 'survival
      of the fittest' content within a Web page, the veracity of these resources can be
      assured through careful monitoring, moderation, and operation of the
      collaborationware in a closed and secure digital environment. Empirical research
      is still needed to build our pedagogic evidence base about the different aspects
      of these tools in the context of medical/health education. SUMMARY AND
      CONCLUSION: If effectively deployed, wikis, blogs and podcasts could offer a way
      to enhance students', clinicians' and patients' learning experiences, and deepen
      levels of learners' engagement and collaboration within digital learning
      environments. Therefore, research should be conducted to determine the best ways
      to integrate these tools into existing e-Learning programmes for students, health
      professionals and patients, taking into account the different, but also
      overlapping, needs of these three audience classes and the opportunities of
      virtual collaboration between them. Of particular importance is research into
      novel integrative applications, to serve as the "glue" to bind the different
      forms of Web-based collaborationware synergistically in order to provide a
      coherent wholesome learning experience.

PMID- 16911780
TI  - Use of email in a family practice setting: opportunities and challenges in
      patient- and physician-initiated communication.
AB  - BACKGROUND: Electronic mail (email) has the potential to improve communication
      between physicians and patients. METHODS: We conducted two research studies in a
      family practice setting: 1) a brief, anonymous patient survey of a convenience
      sample to determine the number of clinic patients receptive to communicating with
      their physician via email, and 2) a randomized, controlled pilot study to assess
      the feasibility of providing health education via email to family practice
      patients. RESULTS: Sixty-eight percent of patients used email, and the majority
      of those (80%) were interested in using email to communicate with the clinic. The
      majority also reported that their email address changed less frequently than
      their home address (65%, n = 173) or telephone number (68%, n = 181). Forty-two
      percent were willing to pay an out-of-pocket fee to have email access to their
      physicians. When evaluating email initiated by the clinic, 26% of otherwise
      eligible patients could not participate because they lacked email access; those
      people were more likely to be black and to be insured through Medicaid. Twenty
      four subjects agreed to participate, but one-third failed to return the required
      consent form by mail. All participants who received the intervention emails said
      they would like to receive health education emails in the future. CONCLUSION: Our
      survey results show that patients are interested in email communication with the
      family practice clinic. Our feasibility study also illustrates important
      challenges in physician-initiated electronic communication. The 'digital divide' 
      decreased access to electronic technologies in lower income groups - is an
      ethical concern in the use of email for patient-physician communication.

PMID- 16911781
TI  - Prostate-specific membrane antigen is undetectable in choroidal neovascular
      membrane.
AB  - BACKGROUND: Choroidal neovascular membrane (CNVM) is one of the leading causes of
      severe visual loss and is often associated with age-related macular degeneration
      (AMD). Various modalities of treatment, including photocoagulation and surgery,
      are being considered as options, but with limited success. Prostate-specific
      membrane antigen (PSMA) is a type II membrane glycoprotein expressed in benign
      and malignant prostatic tissues, in some non-prostatic tissues, and in the
      endothelium of tumor-associated neovasculature of non-prostatic neoplasm. Some
      studies have suggested that the expression of PSMA is restricted to endothelium
      from tumor-associated neovasculature and might be stimulated by some tumor
      secreted angiogenic factors. However, no previous study demonstrating PSMA
      expression in non-related tumor neovasculature, such as CNVM, has been performed
      to date. Furthermore, demonstration of PSMA expression in CNVM in AMD patients
      could reveal a novel target for antineovascular therapy. The purpose of this
      study was to evaluate the immunohistochemical expression of PSMA in CNVM from
      AMD. METHODS: Immunohistochemical analysis, with a standard avidin-biotin complex
      technique, was performed using an anti-PSMA mouse monoclonal antibody in 30
      specimens of surgically excised CNVM from AMD patients. Antibody to an
      endothelial cell specific marker, factor VIII, was used to confirm the location
      of the endothelial cells. RESULTS: The angiogenic microvessels of the 30 cases
      demonstrated negative staining to PSMA while factor VIII was expressed in all
      cases. Seventy-five percent of the secretory-acinar epithelium of the prostatic
      hyperplasia specimen stained positive, confirming that the immunohistochemical
      technique was correctly performed. CONCLUSION: The absence of PSMA expression in
      non-tumoral neovasculature supports the theory, previously suggested, that
      endothelial cell PSMA expression may be stimulated by one or more tumor-secreted
      angiogenic factors. Angiogenesis is very important in neoplasia and the
      endothelial expression of PSMA in tumor-associated neovasculature may represent a
      target for antineovasculature-based therapy. The absence of PSMA expression in
      CNVM suggests that PSMA may not be a potential target for antineovasculature
      based therapy.

PMID- 16911782
TI  - Telomerase activity, estrogen receptors (alpha, beta), Bcl-2 expression in human
      breast cancer and treatment response.
AB  - BACKGROUND: The mechanism for maintaining telomere integrity is controlled by
      telomerase, a ribonucleoprotein enzyme that specifically restores telomere
      sequences, lost during replication by means of an intrinsic RNA component as a
      template for polymerization. Among the telomerase subunits, hTERT (human
      telomerase reverse transcriptase) is expressed concomitantly with the activation
      of telomerase. The role of estrogens and their receptors in the transcriptional
      regulation of hTERT has been demonstrated. The current study determines the
      possible association between telomerase activity, the expression of both
      molecular forms of estrogen receptor (ERalpha and ERbeta) and the protein bcl-2,
      and their relative associations with clinical parameters. METHODS: Tissue samples
      from 44 patients with breast cancer were used to assess telomerase activity using
      the TRAP method and the expression of ERalpha, ERbeta and bcl-2 by means of
      immunocytochemical techniques. RESULTS: Telomerase activity was detected in 59%
      of the 44 breast tumors examined. Telomerase activity ranged from 0 to 49.93
      units of total product generated (TPG). A correlation was found between
      telomerase activity and differentiation grade (p = 0.03). The only significant
      independent marker of response to treatment was clinical stage. We found
      differences between the frequency of expression of ERalpha (88%) and ERbeta (36%)
      (p = 0.007); bcl-2 was expressed in 79.5% of invasive breast carcinomas. We also
      found a significant correlation between low levels of telomerase activity and a
      lack of ERbeta expression (p = 0.03). CONCLUSION: Lower telomerase activity was
      found among tumors that did not express estrogen receptor beta. This is the first
      published study demonstrating that the absence of expression of ERbeta is
      associated with low levels of telomerase activity.

PMID- 16911783
TI  - Azithromycin in chronic fatigue syndrome (CFS), an analysis of clinical data.
AB  - BACKGROUND: CFS is a clinical state with defined symptoms, but undefined cause.
      The patients may show a chronic state of immune activation and treatment with an
      antibiotic in this subgroup has been suggested. METHODS: In a retrospective
      study, the response of CFS patients to azithromycin, an antibiotic and
      immunomodulating drug, has been scored from the patients records and compared
      with clinical and laboratory data. Azithromycin was not the first choice therapy,
      but offered when the effect of counseling and L-carnitine was considered
      insufficient by the patient and the clinician. RESULTS: Of the 99 patients
      investigated, 58 reported a decrease in the symptoms by the use of azithromycin.
      These responding patients had lower levels of plasma acetylcarnitine. CONCLUSION:
      The efficacy of azithromycin in the responsive patients could be explained by the
      modulating effect on a chronic primed state of the immune cells of the brain, or
      the activated peripheral immune system. Their lower acetylcarnitine levels may
      reflect a decreased antioxidant defense and/or an increased consumption of
      acetylcarnitine caused by oxidative stress.

PMID- 16911784
TI  - Evolutionary constraints on yeast protein size.
AB  - BACKGROUND: Despite a strong evolutionary pressure to reduce genome size,
      proteins vary in length over a surprisingly wide range also in very compact
      genomes. Here we investigated the evolutionary forces that act on protein size in
      the yeast Saccharomyces cerevisiae utilizing a system-wide bioinformatics
      approach. Data on yeast protein size was compared to global experimental data on
      protein expression, phenotypic pleiotropy, protein-protein interactions, protein
      evolutionary rate and biochemical classification. RESULTS: Comparing the
      experimentally determined abundance of individual proteins, highly expressed
      proteins were found to be consistently smaller than lowly expressed proteins, in
      accordance with the biosynthetic cost minimization hypothesis. Yeast proteins
      able to maintain a high expression level despite a large size tended to belong to
      a very distinct set of protein families, notably nuclear transport and
      translation initiation/elongation. Large proteins have significantly more protein
      protein interactions than small proteins, suggesting that a requirement for
      multiple interaction domains may constitute a positive selective pressure for
      large protein size in yeast. The higher frequency of protein-protein interactions
      in large proteins was not accompanied by a higher phenotypic pleiotropy. Hence,
      the increase in interactions may not reflect an increase in function
      differentiation. Proteins of different sizes also evolved at similar rates.
      Finally, whereas the biological process involved was found to have little
      influence on protein size the biochemical activity exerted by the protein
      represented a dominant factor. More than one third of all biochemical activity
      classes were enriched in one or more size intervals. CONCLUSION: In yeast, there
      is an inverse relationship between protein size and protein expression such that
      highly expressed proteins tend to be of smaller size. Also, protein size is
      moderately affected by protein connectivity and strongly affected by biochemical
      activity. Phenotypic pleiotropy does not seem to affect protein size.

PMID- 16911785
TI  - Plasma osteopontin levels in patients with head and neck cancer and cervix cancer
      are critically dependent on the choice of ELISA system.
AB  - BACKGROUND: The tumor-associated glycoprotein osteopontin (OPN) is discussed as a
      plasma surrogate marker of tumor hypoxia and as an indicator of the presence of
      pleural mesothelioma in asbestos-exposed individuals. The clinical introduction
      of plasma OPN measurements requires the availability of a reliable enzyme-linked
      immunosorbence assay (ELISA). METHODS: We compared previously described and
      currently available ELISA systems on 88 archival plasma samples obtained from
      patients with head and neck or cervix cancer between 20 days before and 171 after
      the start of radiotherapy. RESULTS: Median (range) plasma OPN levels were 667
      (148.8-2095) ng/ml and 9.8 (3.5-189.5) ng/ml for a previously described and a
      newly marketed assay, respectively. Although results for different assays were
      significantly correlated (r = 0.38, p < 0.05, Spearman rank test), between-assay
      factors ranged from 2.0 to 217.9 (median 74.6) in individual patients. OPN levels
      in cervix cancer patients were comparable to those of head and neck cancer
      patients. CONCLUSION: Commercially available OPN ELISA systems produce different
      absolute plasma OPN levels, compromising a comparison of individual patient data
      with published results. However, different assays appear to have a similar
      capacity to rank patients according to plasma OPN level. A review of literature
      data suggests that plasma OPN levels measured even with identical ELISA systems
      can only be compared with caution.

PMID- 16911786
TI  - Impact of DOTS expansion on tuberculosis related outcomes and costs in Haiti.
AB  - BACKGROUND: Implementation of the World Health Organization's DOTS strategy
      (Directly Observed Treatment Short-course therapy) can result in significant
      reduction in tuberculosis incidence. We estimated potential costs and benefits of
      DOTS expansion in Haiti from the government, and societal perspectives. METHODS:
      Using decision analysis incorporating multiple Markov processes (Markov
      modelling), we compared expected tuberculosis morbidity, mortality and costs in
      Haiti with DOTS expansion to reach all of the country, and achieve WHO
      benchmarks, or if the current situation did not change. Probabilities of
      tuberculosis related outcomes were derived from the published literature.
      Government health expenditures, patient and family costs were measured in direct
      surveys in Haiti and expressed in 2003 US$. RESULTS: Starting in 2003, DOTS
      expansion in Haiti is anticipated to cost $4.2 million and result in 63,080 fewer
      tuberculosis cases, 53,120 fewer tuberculosis deaths, and net societal savings of
      $131 million, over 20 years. Current government spending for tuberculosis is
      high, relative to the per capita income, and would be only slightly lower with
      DOTS. Societal savings would begin within 4 years, and would be substantial in
      all scenarios considered, including higher HIV seroprevalence or drug resistance,
      unchanged incidence following DOTS expansion, or doubling of initial and ongoing
      costs for DOTS expansion. CONCLUSION: A modest investment for DOTS expansion in
      Haiti would provide considerable humanitarian benefit by reducing tuberculosis
      related morbidity, mortality and costs for patients and their families. These
      benefits, together with projected minimal Haitian government savings, argue
      strongly for donor support for DOTS expansion.

PMID- 16911787
TI  - An animal model in sheep for biocompatibility testing of biomaterials in
      cancellous bones.
AB  - BACKGROUND: The past years have seen the development of many synthetic bone
      replacements. To test their biocompatibility and ability for osseointegration,
      osseoinduction and -conduction requires their placement within bone preferably in
      an animal experiment of a higher species. METHODS: A suitable experimental animal
      model in sheep with drill holes of 8 mm diameter and 13 mm depth within the
      proximal and distal humerus and femur for testing biocompatibility issues is
      introduced. RESULTS: This present sheep model allows the placing of up to 8
      different test materials within one animal and because of the standardization of
      the bone defect, routine evaluation by means of histomorphometry is easily
      conducted. This method was used successfully in 66 White Alpine Sheep. When the
      drill holes were correctly placed no complications such as spontaneous fractures
      were encountered. CONCLUSION: This experimental animal model serves an excellent
      basis for testing the biocompatibility of novel biomaterials to be used as bone
      replacement or new bone formation enhancing materials.

PMID- 16911788
TI  - Validation and functional annotation of expression-based clusters based on gene
      ontology.
AB  - BACKGROUND: The biological interpretation of large-scale gene expression data is
      one of the paramount challenges in current bioinformatics. In particular, placing
      the results in the context of other available functional genomics data, such as
      existing bio-ontologies, has already provided substantial improvement for
      detecting and categorizing genes of interest. One common approach is to look for
      functional annotations that are significantly enriched within a group or cluster
      of genes, as compared to a reference group. RESULTS: In this work, we suggest the
      information-theoretic concept of mutual information to investigate the
      relationship between groups of genes, as given by data-driven clustering, and
      their respective functional categories. Drawing upon related approaches (Gibbons
      and Roth, Genome Research 12:1574-1581, 2002), we seek to quantify to what extent
      individual attributes are sufficient to characterize a given group or cluster of
      genes. CONCLUSION: We show that the mutual information provides a systematic
      framework to assess the relationship between groups or clusters of genes and
      their functional annotations in a quantitative way. Within this framework, the
      mutual information allows us to address and incorporate several important issues,
      such as the interdependence of functional annotations and combinatorial
      combinations of attributes. It thus supplements and extends the conventional
      search for overrepresented attributes within a group or cluster of genes. In
      particular taking combinations of attributes into account, the mutual information
      opens the way to uncover specific functional descriptions of a group of genes or
      clustering result. All datasets and functional annotations used in this study are
      publicly available. All scripts used in the analysis are provided as additional
      files.

PMID- 16911789
TI  - Limitations of diabetes pharmacotherapy: results from the Vermont Diabetes
      Information System study.
AB  - BACKGROUND: There are a wide variety of medications available for the treatment
      of hyperglycemia in diabetes, including some categories developed in recent
      years. The goals of this study were to describe the glycemic medication profiles
      in a cohort of adult patients enrolled in primary care, to compare the regimens
      with measures of glycemic control, and to describe potential contraindicated
      regimens. METHODS: One thousand and six subjects with diabetes cared for in
      community practices in the Northeast were interviewed at home at the time of
      enrollment in a trial of a diabetes decision support system. Laboratory data were
      obtained directly from the clinical laboratory. Current medications were obtained
      by direct observation of medication containers by a research assistant. RESULTS:
      The median age of subjects was 63 years; 54% were female. The mean A1C was 7.1%,
      with 60% of subjects in excellent glycemic control (A1C < 7%). Ninety percent of
      patients were taking 2 or fewer medications for glycemic control, with a range of
      0 to 4 medications. Insulin was used by 18%. As the number of diabetes
      medications increased from 0 to 4, the A1C increased from 6.5% to 9.2% (p <
      0.001). The association between glycemic control and number of glycemic
      medications was confirmed using logistic regression, controlling for potential
      confounders. Almost 20% of subjects on metformin or thiazolidenediones had
      potential contraindications to these medications. CONCLUSION: Patients with
      diabetes cared for in primary care are on a wide variety of medication
      combinations for glycemic control, though most are on two or fewer medications. A
      greater number of diabetes medications is associated with poorer glycemic
      control, reflecting the limitations of current pharmacotherapy. One quarter of
      patients are on glycemic medications with potential contraindications.

PMID- 16911790
TI  - Evaluating preference weights for the Asthma Symptom Utility Index (ASUI) across
      countries.
AB  - BACKGROUND: The Asthma Symptom Utility Index (ASUI) is a preference-based outcome
      measure used in US clinical trials and cost-effectiveness studies for asthma.
      This study evaluated ASUI preference weights in Europe to determine whether the
      multi-attribute utility function, based on preferences from a US population, is
      generalizable across countries. METHODS: Data were collected from ninety asthma
      patients from Italy, France, and the United Kingdom using the Asthma Control
      Questionnaire, the Asthma Quality of Life Questionnaire, and the ASUI. Subjects
      rated their preferences for 10 asthma health states using a visual analogue scale
      (VAS) and a standard gamble (SG) interview. RESULTS: All multi-symptom states
      showed statistically significant differences (p < 0.001) between countries in
      mean VAS scores. Mean SG utility scores between the US and France and the US and
      Italy demonstrated statistically significant differences (p < 0.001) for three
      states: severe wheeze; moderate cough and wheeze; and moderate cough and dyspnea.
      Because of these differences, the multi-attribute utility functions derived
      within countries were somewhat different. Despite these differences, country
      specific algorithms captured a similar rank ordering of patients by disease
      severity, were strongly correlated (r = 0.971 to 0.995), and demonstrated similar
      relationships with symptom and AQLQ scores. CONCLUSION: Results of this study
      suggest that the ASUI may be a complementary patient-reported outcome for
      clinical studies and may be useful for applications in cost-effectiveness studies
      comparing different asthma treatments.

PMID- 16911791
TI  - Mapping of the methylation pattern of the hMSH2 promoter in colon cancer, using
      bisulfite genomic sequencing.
AB  - The detailed methylation status of CpG sites in the promoter region of hMSH2 gene
      has yet not to be reported. We have mapped the complete methylation status of the
      hMSH2 promoter, a region that contains 75 CpG sites, using bisulfite genomic
      sequencing in 60 primary colorectal cancers. And the expression of hMSH2 was
      detected by immunohistochemistry. The hypermethylation of hMSH2 was detected in
      18.33% (11/60) of tumor tissues. The protein of hMSH2 was detected in 41.67%
      (25/60) of tumor tissues. No hypermethylation of hMSH2 was detected in normal
      tissues. The protein of hMSH2 was detected in all normal tissues. Our study
      demonstrated that hMSH2 hypermethylation and protein expression were associated
      with the development of colorectal cancer.

PMID- 16911792
TI  - Reconsidering the public health failings of the criminal justice system: a
      reflection on the case of Scott Ortiz.
AB  - Throughout most of the world, the primary response to the health and social
      impacts of illicit drug use has been to intensify the enforcement of drug laws.
      The consequences of this policy approach include an unprecedented growth in
      prison populations and increasing concerns regarding drug-related harms within
      prisons and without, including increased risk of HIV and hepatitis C (HCV)
      infection. This has led to calls from public health and prisoner advocacy groups
      to prison authorities to improve health services available in the community and
      those available to prisoners. While considerable progress has been made with
      respect to the growing implementation of HIV and HCV prevention measures within
      some nations' prisons, the case of Scott Ortiz illuminates a new set of
      challenges for prisoners and their advocates as judges often have a faulty
      understanding of public health arguments and data. In this case we see one such
      instance where a judge acts in ways not rooted in sound public health evidence or
      practice to produce a perverse outcome that violates both sound medical and
      judicial objectives.

PMID- 16911793
TI  - Leontiasis ossea and post traumatic cervical cord contusion in polyostotic
      fibrous dysplasia.
AB  - Leontiasis ossea (leonine facies) or cervical canal stenosis are rare
      complications of polyostotic fibrous dysplasia (PFD). This case report documents
      dramatic leontiasis ossea in PFD as well as post traumatic cervical cord
      contusion due to hyperextension injury in a patient with generalized PFD
      involving the cranio-facial bones, axial skeleton and entire spine with secondary
      cervical canal stenosis. Cervical cord contusion has not been reported earlier in
      PFD.

PMID- 16911794
TI  - Validation of using gene expression in mononuclear cells as a marker for hepatic
      cholesterol metabolism.
AB  - HMG-CoA reductase and the LDL receptor are ubiquitously expressed in major
      tissues. Since the liver plays a major role in regulating circulating LDL, it is
      usually of interest to measure the effects of drug or dietary interventions on
      these proteins in liver. In humans, peripheral blood mononuclear cells have been
      used as a surrogate for liver to assess regulation of these genes, although there
      is concern regarding the validity of this approach. The purpose of this study was
      to evaluate the relationship between liver and mononuclear cell expression of HMG
      CoA reductase and the LDL receptor in guinea pigs, a well established model for
      human cholesterol and lipoprotein metabolism. We extracted RNA from liver and
      mononuclear cells of guinea pigs from a previous study where the effects of
      rapamycin, an immunosuppresant drug used for transplant patients, on lipid
      metabolism were evaluated. Guinea pigs were assigned to three different diets
      containing the same amount of fat (15 g/100 g) and cholesterol (0.08 g/100 g) for
      a period of 3 weeks. The only difference among diets was the concentration of
      rapamycin: 0, 0.0028 or 0.028 g/100 g. There were no differences in plasma LDL
      cholesterol (LDL-C) among groups. Values were 78.4 +/- 14.3, 65.8 +/- 17.2 and
      68.4 +/- 45.4 mg/dL (P > 0.05) for guinea pigs treated with 0, low or high doses
      of rapamycin, respectively. The mRNA abundance for the LDL receptor and HMG-CoA
      reductase was measured both in liver (n = 30) and mononuclear cells (n = 22)
      using reverse transcriptase PCR. In agreement with the finding of no changes in
      plasma LDL-C, there were also no differences for the expression of HMG-CoA
      reductase or the LDL receptor among groups. However, a positive correlation was
      found between liver and mononuclear cells for both HMG-CoA reductase (r = 0.613,
      P < 0.01) and the LDL receptor (r = 0.622, P < 0.01). These correlations suggest
      that monocytes can be used in humans as an index for liver to assess diet and
      drug effects on the expression of HMG-CoA reductase and the LDL receptor.

PMID- 16911796
TI  - A method for exposing rodents to resuspended particles using whole-body
      plethysmography.
AB  - BACKGROUND: Epidemiological studies have reported increased risks of
      cardiopulmonary-related hospitalization and death in association with exposure to
      elevated levels of particulate matter (PM) across a wide range of urban areas. In
      response to these findings, researchers have conducted animal inhalation
      exposures aimed at reproducing the observed toxicologic effects. However, it is
      technically difficult to quantitate the actual amount of PM delivered to the lung
      in such studies, and dose is frequently estimated using default respiration
      parameters. Consequently, the interpretation of PM-induced effects in rodents
      exposed via whole-body inhalation is often compromised by the inability to
      determine deposited dose. To address this problem, we have developed an exposure
      system that merges the generation of dry, aerosolized particles with whole-body
      plethysmography (WBP), thus permitting inhalation exposures in the unrestrained
      rat while simultaneously obtaining data on pulmonary function. RESULTS: This
      system was validated using an oil combustion-derived particle (HP12) at three
      nominal concentrations (3, 12, and 13 mg/m3) for four consecutive exposure days
      (6 hr/day); a single 6-hour exposure to 13 mg/m3 of HP12 was also conducted.
      These results demonstrated that the system was both reliable and consistent over
      these exposure protocols, achieving average concentrations that were within 10%
      of the targeted concentration. In-line filters located on the exhaust outlets of
      individual WBP chambers showed relative agreement in HP12 mass for each day and
      were not statistically different when compared to one another (p = 0.16).
      Temperatures and relative humidities were also similar between chambers during PM
      and air exposures. Finally, detailed composition analyses of both HP12 filter and
      bulk samples showed that grinding and aerosolization did not change particle
      chemistry. CONCLUSION: The results of this study demonstrate that it is possible
      to expose rodents to resuspended, dry PM via whole-body inhalation while these
      animals are maintained in WBP chambers. This new methodology should significantly
      improve the ability to assess dosimetry under minimally stressful exposure
      conditions.

PMID- 16911795
TI  - Immediate effects of spinal manipulation on thermal pain sensitivity: an
      experimental study.
AB  - BACKGROUND: The underlying causes of spinal manipulation hypoalgesia are largely
      unknown. The beneficial clinical effects were originally theorized to be due to
      biomechanical changes, but recent research has suggested spinal manipulation may
      have a direct neurophysiological effect on pain perception through dorsal horn
      inhibition. This study added to this literature by investigating whether spinal
      manipulation hypoalgesia was: a) local to anatomical areas innervated by the
      lumbar spine; b) correlated with psychological variables; c) greater than
      hypoalgesia from physical activity; and d) different for A-delta and C-fiber
      mediated pain perception. METHODS: Asymptomatic subjects (n = 60) completed
      baseline psychological questionnaires and underwent thermal quantitative sensory
      testing for A-delta and C-fiber mediated pain perception. Subjects were then
      randomized to ride a stationary bicycle, perform lumbar extension exercise, or
      receive spinal manipulation. Quantitative sensory testing was repeated 5 minutes
      after the intervention period. Data were analyzed with repeated measures ANOVA
      and post-hoc testing was performed with Bonferroni correction, as appropriate.
      RESULTS: Subjects in the three intervention groups did not differ on baseline
      characteristics. Hypoalgesia from spinal manipulation was observed in lumbar
      innervated areas, but not control (cervical innervated) areas. Hypoalgesic
      response was not strongly correlated with psychological variables. Spinal
      manipulation hypoalgesia for A-delta fiber mediated pain perception did not
      differ from stationary bicycle and lumbar extension (p > 0.05). Spinal
      manipulation hypoalgesia for C-fiber mediated pain perception was greater than
      stationary bicycle riding (p = 0.040), but not for lumbar extension (p = 0.105).
      CONCLUSION: Local dorsal horn mediated inhibition of C-fiber input is a potential
      hypoalgesic mechanism of spinal manipulation for asymptomatic subjects, but
      further study is required to replicate this finding in subjects with low back
      pain.

PMID- 16911797
TI  - Initiation of male sperm-transfer behavior in Caenorhabditis elegans requires
      input from the ventral nerve cord.
AB  - BACKGROUND: The Caenorhabditis elegans male exhibits a stereotypic behavioral
      pattern when attempting to mate. This behavior has been divided into the
      following steps: response, backing, turning, vulva location, spicule insertion,
      and sperm transfer. We and others have begun in-depth analyses of all these steps
      in order to understand how complex behaviors are generated. Here we extend our
      understanding of the sperm-transfer step of male mating behavior. RESULTS: Based
      on observation of wild-type males and on genetic analysis, we have divided the
      sperm-transfer step of mating behavior into four sub-steps: initiation, release,
      continued transfer, and cessation. To begin to understand how these sub-steps of
      sperm transfer are regulated, we screened for ethylmethanesulfonate (EMS)-induced
      mutations that cause males to transfer sperm aberrantly. We isolated an allele of
      unc-18, a previously reported member of the Sec1/Munc-18 (SM) family of proteins
      that is necessary for regulated exocytosis in C. elegans motor neurons. Our
      allele, sy671, is defective in two distinct sub-steps of sperm transfer:
      initiation and continued transfer. By a series of transgenic site-of-action
      experiments, we found that motor neurons in the ventral nerve cord require UNC-18
      for the initiation of sperm transfer, and that UNC-18 acts downstream or in
      parallel to the SPV sensory neurons in this process. In addition to this neuronal
      requirement, we found that non-neuronal expression of UNC-18, in the male gonad,
      is necessary for the continuation of sperm transfer. CONCLUSION: Our division of
      sperm-transfer behavior into sub-steps has provided a framework for the further
      detailed analysis of sperm transfer and its integration with other aspects of
      mating behavior. By determining the site of action of UNC-18 in sperm-transfer
      behavior, and its relation to the SPV sensory neurons, we have further defined
      the cells and tissues involved in the generation of this behavior. We have shown
      both a neuronal and non-neuronal requirement for UNC-18 in distinct sub-steps of
      sperm-transfer behavior. The definition of circuit components is a crucial first
      step toward understanding how genes specify the neural circuit and hence the
      behavior.

PMID- 16911798
TI  - Preparing clinical-grade myeloid dendritic cells by electroporation-mediated
      transfection of in vitro amplified tumor-derived mRNA and safety testing in stage
      IV malignant melanoma.
AB  - BACKGROUND: Dendritic cells (DCs) have been used as vaccines in clinical trials
      of immunotherapy of cancer and other diseases. Nonetheless, progress towards the
      use of DCs in the clinic has been slow due in part to the absence of standard
      methods for DC preparation and exposure to disease-associated antigens. Because
      different ex vivo exposure methods can affect DC phenotype and function
      differently, we studied whether electroporation-mediated transfection
      (electrotransfection) of myeloid DCs with in vitro expanded RNA isolated from
      tumor tissue might be feasible as a standard physical method in the preparation
      of clinical-grade DC vaccines. METHODS: We prepared immature DCs (IDCs) from
      CD14+ cells isolated from leukapheresis products and extracted total RNA from
      freshly resected melanoma tissue. We reversely transcribed the RNA while
      attaching a T7 promoter to the products that we subsequently amplified by PCR. We
      transcribed the amplified cDNA in vitro and introduced the expanded RNA into IDCs
      by electroporation followed by DC maturation and cryopreservation. Isolated and
      expanded mRNA was analyzed for the presence of melanoma-associated tumor antigens
      gp100, tyrosinase or MART1. To test product safety, we injected five million DCs
      subcutaneously at three-week intervals for up to four injections into six
      patients suffering from stage IV malignant melanoma. RESULTS: Three preparations
      contained all three transcripts, one isolate contained tyrosinase and gp100 and
      one contained none. Electrotransfection of DCs did not affect viability and
      phenotype of fresh mature DCs. However, post-thaw viability was lower (69 +/- 12
      percent) in comparison to non-electroporated cells (82 +/- 12 percent; p =
      0.001). No patient exhibited grade 3 or 4 toxicity upon DC injections.
      CONCLUSION: Standardized preparation of viable clinical-grade DCs transfected
      with tumor-derived and in vitro amplified mRNA is feasible and their
      administration is safe.

PMID- 16911799
TI  - Identifying conditions for inducible protein production in E. coli: combining a
      fed-batch and multiple induction approach.
AB  - BACKGROUND: In the interest of generating large amounts of recombinant protein,
      inducible systems have been studied to maximize both the growth of the culture
      and the production of foreign proteins. Even though thermo-inducible systems were
      developed in the late 1970's, the number of studies that focus on strategies for
      the implementation at bioreactor scale is limited. In this work, the
      bacteriophage lambda PL promoter is once again investigated as an inducible
      element but for the production of green fluorescent protein (GFP). Culture
      temperature, induction point, induction duration and number of inductions were
      considered as factors to maximize GFP production in a 20-L bioreactor. RESULTS:
      It was found that cultures carried out at 37 degrees C resulted in a growth
      associated production of GFP without the need of an induction at 42 degrees C.
      Specific production was similar to what was achieved when separating the growth
      and production phases. Shake flask cultures were used to screen for desirable
      operating conditions. It was found that multiple inductions increased the
      production of GFP. Induction decreased the growth rate and substrate yield
      coefficients; therefore, two time domains (before and after induction) having
      different kinetic parameters were created to fit a model to the data collected.
      CONCLUSION: Based on two batch runs and the simulation of culture dynamics, a pre
      defined feeding and induction strategy was developed to increase the volumetric
      yield of a temperature regulated expression system and was successfully
      implemented in a 20-L bioreactor. An overall cell density of 5.95 g DW l(-1) was
      achieved without detriment to the cell specific production of GFP; however, the
      production of GFP was underestimated in the simulations due to a significant
      contribution of non-growth associated product formation under limiting nutrient
      conditions.

PMID- 16911800
TI  - H-NS controls metabolism and stress tolerance in Escherichia coli O157:H7 that
      influence mouse passage.
AB  - BACKGROUND: H-NS is a DNA-binding protein with central roles in gene regulation
      and nucleoid structuring in Escherichia coli. There are over 60 genes that are
      influenced by H-NS many of which are involved in metabolism. To determine the
      significance of H-NS-regulated genes in metabolism and stress tolerance, an hns
      mutant of E. coli O157:H7 was generated (hns::nptI, FRIK47001P) and its growth,
      metabolism, and gastrointestinal passage compared to the parent strain (43895)
      and strain FRIK47001P harboring pSC0061 which contains a functional hns and 90-bp
      upstream of the open-reading frame. RESULTS: The hns mutant grew slower and was
      non-motile in comparison to the parent strain. Carbon and nitrogen metabolism was
      significantly altered in the hns mutant, which was incapable of utilizing 42
      carbon, and 19 nitrogen sources that the parent strain metabolized. Among the non
      metabolized substrates were several amino acids, organic acids, and key metabolic
      intermediates (i.e., pyruvate) that limit carbon acquisition and energy
      generation. Growth studies determined that the parent strain grew in LB
      containing 14 to 15% bile or bile salts, while the hns mutant grew in 6.5 and 9%
      of these compounds, respectively. Conversely, log-phase cells of the hns mutant
      were significantly (p < 0.05) more acid tolerant than the parent strain and hns
      mutant complemented with pSC0061. In mouse passage studies, the parent strain was
      recovered at a higher frequency (p < 0.01) than the hns mutant regardless of
      whether log- or stationary-phase phase cells were orally administered.
      CONCLUSION: These results demonstrate that H-NS is a powerful regulator of carbon
      and nitrogen metabolism as well as tolerance to bile salts. It is likely that the
      metabolic impairments and/or the reduced bile tolerance of the E. coli O157:H7
      hns mutant decreased its ability to survive passage through mice. Collectively,
      these results expand the influence of H-NS on carbon and nitrogen metabolism and
      highlight its role in the ability of O157:H7 strains to respond to changing
      nutrients and conditions encountered in the environment and its hosts.

PMID- 16911801
TI  - Immediate and longer term impact of the varicella shortage on children 18 and 24
      months of age in a community population.
AB  - BACKGROUND: Little is known about the impact of the recent varicella vaccine
      shortage. To assess the temporal trend in varicella vaccine administration before
      18 and 24 months of age in a community cohort of children prior to, during and
      after the recent varicella vaccine shortage. And to compare the temporal trends
      in varicella vaccinations to trends of an older, more widely accepted vaccine,
      the MMR. METHODS: Community population-based birth cohorts were identified who
      were eligible for the varicella vaccination before, during and after the 2001 to
      2002 varicella vaccine shortage. Only children (84% of all) who remained in the
      community through their second birthday were included. For each child in the
      cohort, the medical records and immunization registry records from both medical
      facilities in the county were reviewed to identify the dates and sites for all
      varicella immunizations given. In addition to varicella immunizations, the dates
      of all MMR vaccinations were recorded. Additional data abstracted included the
      child's birth date, gender and dates of any recognized cases of chickenpox up
      through age 24 months. RESULTS: Of the 2,512 children in the birth cohorts, 50.8%
      were boys. In the three cohorts combined, 81.1% of the boys and 79.3% of the
      girls (p = 0.30) received the varicella vaccine by age 24 months. The pre
      shortage community rate of varicella immunization was 79.7% by 24 months of age.
      During the varicella vaccine shortage, the rate of varicella immunization by 24
      months fell to 77.2%. Only 6 additional children received a "catch-up"
      immunization by 36 months of age. In the post shortage period the community 24
      month immunization rate rebounded to a level higher than the pre-shortage rate
      84.0%. During the almost three years of observation, the MMR immunization rate by
      age 24 months was constant (87%). CONCLUSION: The varicella shortage was
      associated with an immediate drop in the 24-month varicella immunizations rate
      but rebounded quickly to above pre-shortage rates. In this community the only
      long term impact of the varicella vaccine shortage may be on the small number of
      children who still had not received catch-up varicella immunizations by 36 months
      of age.

PMID- 16911802
TI  - Alexithymia and anxiety in female chronic pain patients.
AB  - OBJECTIVES: Alexithymia is highly prevalent among chronic pain patients. Pain is
      a remarkable cause for high levels of chronic anxiety. The purpose of this study
      was to investigate the prevalence of alexithymia and to determine anxiety levels
      among DSM-IV somatoform pain disorder (chronic pain) female patients and to
      examine the relationship between alexithymia and the self-reporting of pain.
      METHODS: Thirty adult females (mean age: 34.63 +/- 10.62 years), who applied to
      the outpatient psychiatry clinic at a public hospital with the diagnosis of
      chronic pain disorder (DSM-IV), were included in the study. Thirty seven healthy
      females (mean age: 34.46 +/- 7.43 years), who matched for sociodemographic
      features with the patient group, consisted the control group. A sociodemographic
      data form, 26-item Toronto Alexithymia Scale (TAS-26), Spielberger Trait Anxiety
      Inventory (STAI) were administered to each subject and information was obtained
      on several aspects of the patients' pain, including intensity (measured by VAS),
      and duration. RESULTS: Chronic pain patients were found significantly more
      alexithymic than controls. There was a positive correlation between TAS-26 scores
      and the duration of pain. The alexithymic and nonalexithymic group did not differ
      in their perception of pain. Neither positive correlation nor significant
      difference was found between alexithymia and trait anxiety in pain patients.
      DISCUSSION: Alexithymia may be important in addressing the diversity of
      subjective factors involved in pain. The conceptualization of alexithymia as a
      personality trait as well as a secondary state reaction is underlined by our
      data.

PMID- 16911803
TI  - Interoceptive hypersensitivity and interoceptive exposure in patients with panic
      disorder: specificity and effectiveness.
AB  - BACKGROUND: Interoceptive exposure has been validated as an effective component
      of cognitive behavioral therapy (CBT) for the treatment of panic disorder but has
      hitherto received little research attention. We examined the effectiveness of
      various interoceptive exposure exercises using the Body Sensations Questionnaire
      (BSQ) (Chambless et al., 1984). METHODS: We first performed an exploratory
      principal factor analysis of all the items contained in the BSQ to obtain
      meaningful dimensions of interoceptive fears. Next, we examined the correlations
      between each interoceptive exposure task's degree of similarity to panic attacks
      and each BSQ factor and then examined whether the BSQ factor scores decreased in
      comparison with the baseline values when the corresponding exposure tasks were
      successfully completed by the subjects. RESULTS: The factor analyses revealed
      four factors, which we named "pseudoneurological fears", "gastrointestinal
      fears", "cardiorespiratory fears" and "fears of dissociative feelings." Among the
      nine interoceptive exposure tasks, 'hyperventilation', 'shaking head', 'holding
      breath' and 'chest breathing' were considered to reproduce pseudoneurological
      symptoms, 'breathing through a straw' was considered to reproduce
      gastrointestinal symptoms, and 'spinning' was considered to reproduce both
      pseudoneurological and dissociative symptoms; none of the interoceptive exercises
      were found to reproduce cardiorespiratory symptoms. Among each group of patients
      for whom 'hyperventilation', 'holding breath', 'spinning' or 'chest breathing'
      was effective, a significant improvement in the BSQ pseudoneurological fears
      factor scores was observed. On the other hand, no significant difference between
      the baseline and endpoint values of the BSQ gastrointestinal fears or the BSQ
      fears of dissociative feelings factor scores were observed among the patients for
      whom 'spinning' or 'breathing through a straw' was effective. CONCLUSION: Several
      interoceptive exposure tasks were particularly effective in reducing
      pseudoneurological fears. New interoceptive tasks, especially tasks related to
      cardiorespiratory and dissociative feelings, are needed.

PMID- 16911804
TI  - Leader (L) and L* proteins of Theiler's murine encephalomyelitis virus (TMEV) and
      their regulation of the virus' biological activities.
AB  - Theiler's murine encephalomyelitis virus (TMEV) is divided into two subgroups on
      the basis of their different biological activities. GDVII subgroup strains
      produce fatal poliomyelitis in mice without virus persistence or demyelination.
      In contrast, TO subgroup strains induce demyelinating disease with virus
      persistence in the spinal cords of weanling mice. Two proteins, whose open
      reading frames are located in the N-terminus of the polyprotein, recently have
      been reported to be important for TMEV biological activities. One is leader (L)
      protein and is processed from the most N-terminus of the polyprotein; its
      function is still unknown. Although the homology of capsid proteins between DA (a
      representative strain of TO subgroup) and GDVII strains is over 94% at the amino
      acid level, that of L shows only 85%. Therefore, L is thought to be a key protein
      for the subgroup-specific biological activities of TMEV. Various studies have
      demonstrated that L plays important roles in the escape of virus from host immune
      defenses in the early stage of infection. The second protein is a 17-18 kDa
      protein, L*, which is synthesized out-of-frame with the polyprotein. Only TO
      subgroup strains produce L* since GDVII subgroup strains have an ACG rather than
      AUG at the initiation site and therefore do not synthesize L*. 'Loss and gain of
      function' experiments demonstrate that L* is essential for virus growth in
      macrophages, a target cell for TMEV persistence. L* also has been demonstrated to
      be necessary for TMEV persistence and demyelination. Further analysis of L and L*
      will help elucidate the pathomechanism(s) of TMEV-induced demyelinating disease.

PMID- 16911805
TI  - Genome-wide gene expression profiling of human mast cells stimulated by IgE or
      FcepsilonRI-aggregation reveals a complex network of genes involved in
      inflammatory responses.
AB  - BACKGROUND: Mast cells are well established effectors of IgE-triggered allergic
      reactions and immune responses to parasitic infections. Recent studies indicate
      that mast cells may play roles in adaptive and innate immunity, suggesting an
      innovative view of the regulation of immune responses. Here, we profiled the
      transcriptome of human mast cells sensitized with IgE alone, or stimulated by
      FcepsilonRI aggregation. RESULTS: Our data show that among 8,793 genes examined,
      559 genes are differentially regulated in stimulated mast cells when compared
      with resting/unstimulated mast cells. The major functional categories of
      upregulated genes include cytokines, chemokines, and other genes involved in
      innate and adaptive immune-responses. We observed the increased expression of
      over 63 gene-transcripts following IgE-sensitization alone. Our data was
      validated using Real-Time-PCR; ELISA and western blot. We confirmed that IgE
      alone does not trigger mast cell-immediate responses, such as calcium signals,
      degranulation or protein-phosphorylation. CONCLUSION: This report represents a
      substantial advance in our understanding of the genome wide effects triggered by
      "passive sensitization" or active stimulation of human mast cells, supporting
      mast cells' potential involvement in a wide range of inflammatory responses.

PMID- 16911806
TI  - Linking the global positioning system (GPS) to a personal digital assistant (PDA)
      to support tuberculosis control in South Africa: a pilot study.
AB  - BACKGROUND: Tuberculosis (TB) is the leading clinical manifestation of HIV
      infection and caseloads continue to increase in high HIV prevalence settings. TB
      treatment is prolonged and treatment interruption has serious individual and
      public health consequences. We assessed the feasibility of using a handheld
      computing device programmed with customised software and linked to a GPS
      receiver, to assist TB control programmes to trace patients who interrupt
      treatment in areas without useful street maps. In this proof of concept study, we
      compared the time taken to re-find a home comparing given residential addresses
      with a customised personalised digital assistant linked to a global positioning
      system (PDA/GPS) device. Additionally, we assessed the feasibility of using
      aerial photographs to locate homes. RESULTS: The study took place in two
      communities in Greater Johannesburg, South Africa: Wheillers Farm, a relatively
      sparsely populated informal settlement, and a portion of Alexandra, an urban
      township with densely populated informal settlements. Ten participants in each
      community were asked to locate their homes on aerial photographs. Nine from
      Wheillers Farm and six from Alexandra were able to identify their homes. The
      total time taken by a research assistant, unfamiliar with the area, to locate 10
      homes in each community using the given addresses was compared with the total
      time taken by a community volunteer with half an hour of training to locate the
      same homes using the device. Time taken to locate the ten households was reduced
      by 20% and 50% in each community respectively using the PDA/GPS device.
      CONCLUSION: In this pilot study we show that it is feasible to use a simple
      PDA/GPS device to locate the homes of patients. We found that in densely
      populated informal settlements, GPS technology is more accurate than aerial
      photos in identifying homes and more efficient than addresses provided by
      participants. Research assessing issues of, confidentiality and cost
      effectiveness would have to be undertaken before implementing PDA/GPS - based
      technology for this application. However, this PDA/GPS device could be used to
      reduce part of the burden on TB control programs.

PMID- 16911807
TI  - Quantification of damage in DNA recovered from highly degraded samples--a case
      study on DNA in faeces.
AB  - BACKGROUND: Poorly preserved biological tissues have become an important source
      of DNA for a wide range of zoological studies. Measuring the quality of DNA
      obtained from these samples is often desired; however, there are no widely used
      techniques available for quantifying damage in highly degraded DNA samples. We
      present a general method that can be used to determine the frequency of
      polymerase blocking DNA damage in specific gene-regions in such samples. The
      approach uses quantitative PCR to measure the amount of DNA present at several
      fragment sizes within a sample. According to a model of random degradation the
      amount of available template will decline exponentially with increasing fragment
      size in damaged samples, and the frequency of DNA damage (lambda) can be
      estimated by determining the rate of decline. RESULTS: The method is illustrated
      through the analysis of DNA extracted from sea lion faecal samples. Faeces
      contain a complex mixture of DNA from several sources and different components
      are expected to be differentially degraded. We estimated the frequency of DNA
      damage in both predator and prey DNA within individual faecal samples. The
      distribution of fragment lengths for each target fit well with the assumption of
      a random degradation process and, in keeping with our expectations, the estimated
      frequency of damage was always less in predator DNA than in prey DNA within the
      same sample (mean lambda(predator) = 0.0106 per nucleotide; mean lambda(prey) =
      0.0176 per nucleotide). This study is the first to explicitly define the amount
      of template damage in any DNA extracted from faeces and the first to quantify the
      amount of predator and prey DNA present within individual faecal samples.
      CONCLUSION: We present an approach for characterizing mixed, highly degraded PCR
      templates such as those often encountered in ecological studies using non
      invasive samples as a source of DNA, wildlife forensics investigations and
      ancient DNA research. This method will allow researchers to measure template
      quality in order to evaluate alternate sources of DNA, different methods of
      sample preservation and different DNA extraction protocols. The technique could
      also be applied to study the process of DNA decay.

PMID- 16911808
TI  - Surgical treatment of malignant involvement of the inferior vena cava.
AB  - BACKGROUND: Resection and replacement of the inferior vena cava to remove
      malignant disease is a formidable procedure. The purpose of this review is to
      describe our experience with regard to patient selection, operative technique,
      and early and late outcome. METHODS: The authors retrospectively reviewed a 12
      year series of 11 patients; there were 10 males, with a mean age 57 +/- 13 years
      (range 27-72) who underwent caval thrombectomy and/or resection for primary (n =
      9) or recurrent (n = 2) vena cava tumours. Tumour location and type, clinical
      presentation, the segment of vena cava treated, graft patency, and tumour
      recurrence and survival data were collected. Late follow-up data were available
      for all patients. Graft patency was determined before hospital discharge and in
      follow-up by CT scan or ultrasonography. More than 80% of patients had symptoms
      from their caval involvement. The most common pathologic diagnosis was renal cell
      carcinoma (n = 6), and hepatocarcinoma (n = 2). In all but 2 patients, inferior
      vena cava surgical treatment was associated with multivisceral resection,
      including extended nephrectomy (n = 5), resection of neoplastic mass (n = 3),
      major hepatic resection (n = 2), and adrenal gland resection (n = 1). Prosthetic
      repair was performed in 5 patients (45%). RESULTS: There were no early deaths.
      Major complications occurred in 1 patient (9%). Mean length of stay was 16 days.
      Late graft thrombosis or infection did not occur. The mean follow-up was 22.7
      months (range 6-60). There have been no other late graft-related complications.
      All late deaths were caused by the progression of malignant disease and the
      actuarial survival rate was 100% at 1 year. Mean survival was 31 months (median
      15). CONCLUSION: Aggressive surgical management may offer the only chance for
      cure or palliation for patients with primary or secondary caval tumours. Our
      experience confirms that vena cava surgery for tumours may be performed safely
      with low graft-related morbidity and good patency in carefully selected patients.

PMID- 16911809
TI  - Remission and relapse in psychosis: operational definitions based on case-note
      data.
AB  - BACKGROUND: In psychosis, the prime indicator of outcome has been relapse, but
      hospital readmission can no longer be used for this purpose. Researchers now
      require methods for assessing relapse that are objective, blind, reliable and
      valid. We describe the reliability and validity of such a technique using case
      notes. METHOD: Information from routine clinical notes of participants in the
      Lambeth Early Onset (LEO) study (less all references that would unblind the
      assessor) were recorded on a form divided into 1-month sections. Operational
      definitions of remission and relapse enabled clinicians to identify remissions
      and relapses blindly from the summary information. We calculated reliability
      regarding both the fact and the timing of remission and relapse. PANSS ratings at
      6 and 18 months provided a measure of validity. RESULTS: The kappa value for the
      identification of remission by individuals ranged from 0.64 to 0.82, while that
      for consensus between paired raters was 0.56. The corresponding values for
      relapse were 0.57-0.59 and 0.71. Intra-class correlations for time to remission
      and to relapse were very high. Raters guessed correctly whether the participants
      came from the intervention or control group on 60-75% of occasions. Independent
      PANSS ratings were strongly related to the remission/relapse status of
      participants. CONCLUSIONS: The reliability of the technique described here was
      moderate to good, its validity was good, and it provides a useful and timely
      addition to methods of evaluating remission and relapse in psychosis. On the
      basis of our experience, we recommend consensus rather than individual ratings.

PMID- 16911810
TI  - Additional confirmation for the effect of environmental light intensity on the
      seasonality of human conceptions.
AB  - Causality for the seasonality of human births, which affects populations
      wordwide, has been a profound mystery for nearly two centuries. Most explanations
      for seasonality fail because of inconsistent global application. In two previous
      studies, Cummings (2002, 2003) hypothesized that human reproduction has been
      responsive to changes in both seasonal environmental light intensity (surface
      luminosity) and photoperiod. Except at higher latitudes, photoperiod is of
      secondary importance to that of environmental light intensity. Because of a lack
      of data, the presence or lack of cloud cover is used as a general proxy for
      environmental light intensity. These studies show a positive correlation between
      conceptual seasonality and cloud cover on a worldwide basis, and propose that
      there is a delay between exposure to increased light and the onset of
      conceptions. This delay is three months at higher latitudes and one to two months
      for lower latitudes. Both studies suggest that an excellent means of hypothesis
      confirmation would be to provide one or more examples of how a seasonal change in
      cloud cover might alter the number of conceptions in subsequent months. The
      present study tests this hypothesis. The percentage of possible sunshine and
      averaged sunshine hours are used to investigate their influence on seasonality of
      births in Germany and the Netherlands. The evidence shows that a seasonal change
      in environmental light intensity preceded a change in the peak months for
      conceptions in Germany and the Netherlands. Although secondary influences are
      possible, the primary reason for this transition in peak conceptual months seems
      to be related to the seasonal changes in environmental light intensity for both
      countries. Although this transitional relationship was predicted in Cummings
      (2002, 2003), further research is required, especially with regard to more
      precise measurements of environmental light intensity and its physiological
      effect on the human endocrine system.

PMID- 16911811
TI  - Skin on GV01 acupoint in colonic inflammatory states: tenderness and neurogenic
      inflammation.
AB  - GV01 is one of the most effective acupoints to treat diarrhea in humans and
      animals. The present study showed that skin on the GV01 acupoint reveals
      tenderness and neurogenic inflammation in colonic inflammatory states, but not in
      normal healthy states.

PMID- 16911812
TI  - Lateral impact injuries with side airbag deployments--a descriptive study.
AB  - The present study was designed to provide descriptive data on side impact
      injuries in vehicles equipped with side airbags using the United States National
      Automotive Sampling System (NASS). The database was queried with the constraint
      that all vehicles must adhere to the Federal Motor Vehicle Safety Standards FMVSS
      214, injured occupants be in the front outboard seats with no rollovers or
      ejections, and side impacts airbags be deployed in lateral crashes. Out of the
      7812 crashes in the 1997-2004 weighted NASS files, AIS > or = 2 level injuries
      occurred to 5071 occupants. There were 3828 cases of torso-only airbags, 955
      cases of torso-head bag combination, and 288 inflatable tubular structure/curtain
      systems. Side airbags were not attributed to be the cause of head or chest injury
      to any occupant at this level of severity. The predominance of torso-only airbags
      followed by torso-head airbag combination reflected vehicle model years and
      changing technology. Head and chest injuries were coupled for the vast majority
      of occupants with injuries to more than one body region. Comparing literature
      data for side impacts without side airbag deployments, the presence of a side
      airbag decreased AIS=2 head, chest, and extremity injuries when examining raw
      data incidence rates. Although this is the first study to adopt strict inclusion
      exclusion criteria for side crashes with side airbag deployments, future studies
      are needed to assess side airbag efficacy using datasets such as matched-pair
      occupants in side impacts.

PMID- 16911813
TI  - The effect of orlistat and fenofibrate, alone or in combination, on small dense
      LDL and lipoprotein-associated phospholipase A2 in obese patients with metabolic
      syndrome.
AB  - BACKGROUND: Increased concentration of small dense LDL cholesterol (sdLDL-C) and
      activity of lipoprotein-associated phospholipase A2 (Lp-PLA(2)) are considered as
      emerging cardiovascular risk factors and are commonly encountered in subjects
      with metabolic syndrome (MetS). OBJECTIVE: The primary endpoint of this study was
      the effect of orlistat and fenofibrate, alone or in combination, on Lp-PLA(2)
      activity and LDL phenotype in overweight and obese patients (body mass index>28
      kg/m(2)) with MetS. METHODS: Patients (n=89) were prescribed a low-fat low
      calorie diet and were randomly allocated to receive orlistat 120 mg three times
      daily (O group), micronized fenofibrate 200mg/day (F group) or both (OF group)
      for 6 months. RESULTS: Significant reductions of sdLDL-C levels were observed in
      all treatment groups. Groups F and OF experienced a greater reduction in sdLDL-C
      levels (p<0.05) together with a greater increase in LDL particle diameter
      (p<0.05) compared with group O. Total plasma Lp-PLA(2) activity significantly
      decreased in all treatment groups. The reduction of Lp-PLA(2) was more pronounced
      with OF administration compared with each monotherapy (p<0.05). CONCLUSION:
      Orlistat and fenofibrate exhibited favorable effects on Lp-PLA(2) activity and
      LDL phenotype in overweight and obese patients with MetS. Importantly,
      combination treatment had a more favorable effect on these risk factors.

PMID- 16911814
TI  - A new method for electrophysiological identification of antennal pH receptor
      cells in ground beetles: the example of Pterostichus aethiops (Panzer, 1796)
      (Coleoptera, Carabidae).
AB  - The responses of antennal taste sensilla of the ground beetle Pterostichus
      aethiops to 100mM Na(+)-salts and their mixtures with 1 and 10mM NaOH were
      compared. An increase in pH by 0.3-0.6 units in 100mM Na(+)-salt solutions,
      caused by the content of 1mM NaOH, was too small, except for alkaline
      Na(2)HPO(4), to influence the firing rate of the cation cell and pH cell
      significantly. However, different sensitivity of the two cells to increased pH
      was clearly demonstrated when the concentration of NaOH in 100mM stimulating salt
      solutions was increased to 10mM. Increasing pH by 1.2-2 units caused the 1st s
      firing rate to increase by 140-1050% and 0-26% in the pH cell and cation cell,
      respectively. Compared to the buffer series method used for identification of the
      pH receptors in ground beetles earlier, considerably stronger responses of the pH
      cell to a similar increase in pH were observed when the NaOH method was used for
      testing. At the same time, undesirable changes in salt ions concentration that
      occur when stimulating solutions differing by 1-2 pH units are prepared were much
      smaller using the latter method. Behavioural and ecological relevance of the
      results is discussed.

PMID- 16911815
TI  - Systemic pathological alterations caused by Philodryas patagoniensis colubrid
      snake venom in rats.
AB  - Very little is known about the systemic effects caused by Philodryas
      patagoniensis colubrid snake venom. In this work, this venom was tested for its
      ability to induce histopathological changes in rats after its intramuscular,
      subcutaneous or intravenous administration, by light microscopic examination of
      some organs (cerebellum, cerebrum, lung, liver, kidney and heart). Four rats were
      used for each dose of 0.23, 0.45 and 0.90 mg of venom in 0.3 ml of phosphate
      buffered saline solution (pH 7.4). Aliquots of blood were withdrawn at different
      time intervals for enzymatic determination of alanine aminotransferase, aspartate
      aminotransferase and creatine kinase levels. After 2h the animals were killed by
      an overdose of anesthetic, and samples of kidney, heart, liver, lung, cerebrum
      and cerebellum were taken to microscopic examination (hematoxylin and eosin
      stain). Histologically, no abnormality was observed in heart tissue, in none of
      the administration routes of the venom used. However, histological observations
      showed multifocal hemorrhage in cerebellum, cerebrum and lung sections, severe
      peritubular capillary congestion in kidney sections and hydropic degeneration in
      liver sections, when venom was administrated intravenously. The subcutaneous
      route showed similar results to the previous one, with the exception of
      cerebellar hemorrhage. Intramuscularly, neither cerebral nor cerebellar
      hemorrhage was observed. Plasma alanine aminotransferase and aspartate
      aminotransferase increased levels were demonstrated, mainly when venom was
      administered intravenously or subcutaneously. Our results suggest that P.
      patagoniensis venom induces moderate histopathological changes in vital organs of
      rats. These changes are initiated at early stages of the envenomation and may be
      associated with a behavioral or functional abnormality of those organs during
      envenoming.

PMID- 16911816
TI  - Mediators involved in the febrile response induced by Tityus serrulatus scorpion
      venom in rats.
AB  - Tityus serrulatus venom (Tsv) was intraperitoneally (ip) injected at doses of 75,
      150 and 300mug/kg and IL-1beta (2.0 microg/kg) was given intravenously (iv) to
      male Wistar rats. Rectal temperature was measured by radiotelemetry. Vagotomy was
      performed according to Bluthe et al. [1994. Lipopolysaccharide induces sickness
      behaviour in rats by a vagal mediated mechanism. C R Acad. Sci. 317(6), 499-503].
      Cerebrospinal fluid (CSF) and peritoneal fluid (PF) levels of bradykinin (BK)
      were measured by ELISA. B(1) (des-Arg(9)-[Leu(8)]-BK; DALBK) and B(2) kinin
      receptor (icatibant) antagonists (1.0 mg/kg each), the induced nitric oxide
      synthase inhibitor aminoguanidine (50.0 mg/kg), the neuronal nitric oxide
      synthase inhibitor 7-nitroindazole (30.0 mg/kg), the dual cyclooxygenase
      inhibitor ibuprofen (10.0 mg/kg), the selective interleukin-1 receptor antagonist
      IL-ra (2.0 mg/kg) and dipyrone (120 mg/kg) were given ip. Celecoxib (5 mg/kg) was
      given per os (po). Tsv at doses of 75 microg/kg evoked no change in rectal
      temperature while at doses of 150 and 300 microg/kg it promoted long-lasting
      fever (2 degrees C+/-0.1). Tsv (150 microg/kg) increased by nearly 3 and 5 times,
      respectively BK concentration in the CSF and in the PF. Subdiaphragmatic vagotomy
      or 7-nitroindazole reduced, icatibant, DALBK, IL-1ra, aminoguanidine and dipyrone
      abolished, while ibuprofen and celecoxib failed to affect Tsv-induced fever.
      These results suggest that PGs do not play a relevant role, whereas, kinins via
      their B(1) and B(2) receptors, IL-1, nitric oxide and vagal neurotransmission are
      involved in Tsv-induced fever.

PMID- 16911817
TI  - New discoveries of skeletal elements of Hadropithecus stenognathus from
      Andrahomana Cave, southeastern Madagascar.
AB  - Remains of what appears to be a single, subadult Hadropithecus stenognathus were
      recovered from a previously unexcavated site at Andrahomana Cave (southeastern
      Madagascar). Specimens found comprise isolated teeth and cranial fragments
      (including the frontal processes of the orbits), as well as a partial postcranial
      skeleton. They include the first associated fore- and hind-limb bones, confirming
      the hind-limb attributions made by Godfrey and co-workers in 1997, and refuting
      earlier attributions by Lamberton in 1937/1938. Of particular interest here are
      the previously unknown elements, including a sacrum, other vertebrae and ribs,
      some hand bones, and the distal epiphysis of a femur. We briefly discuss the
      functional implications of previously unknown elements. Hadropithecus displayed a
      combination of characters reminiscent of lemurids, others more like those of the
      larger-bodied Old World monkeys, and still others more like those of African
      apes. Yet other characteristics appear unique. Lemurid-like postcranial
      characteristics may be primitive for the Archaeolemuridae. Hadropithecus diverges
      from the Lemuridae in the direction of Archaeolemur, but more extremely so. Thus,
      for example, it exhibits a stronger reduction in the size of the hamulus of the
      hamate, greater anteroposterior compression of the femoral shaft, and greater
      asymmetry of the femoral condyles. Nothing in its postcranial anatomy signals a
      close relationship to either the Indriidae or the Palaeopropithecidae.

PMID- 16911818
TI  - Late Quaternary human settlement patterning in the Jebel Gharbi.
AB  - This paper presents the latest results of geoarchaeological research on the Upper
      Pleistocene sequence in the Jebel Gharbi (previously called Jebel Nafusah), a
      mountain range located in Tripolitania, northwestern Libya. Numerous
      archaeological sites are found adjacent to springs that formed as a consequence
      of tectonic activities. The springs originated when Upper Pleistocene earthquakes
      produced ground displacements that created water outlets, some of which are still
      active. Springs are spread all along the massif and at the foot of the mountains
      in Jebel Gharbi. We suggest that they offered attractive resources to populations
      coming from drier parts of North Africa or the near-by Sahara. The earliest sites
      associated with the springs include Aterian lithic techno-complexes that have
      been dated between 80,000 and 40,000 BP. Since then, these springs have attracted
      many populations, as documented here by settlements belonging to the Later Stone
      Age (Upper Palaeolithic), Iberomaurusian (Late Upper Palaeolithic or
      Epipalaeolithic), Neolithic, Roman period, and present time.

PMID- 16911819
TI  - Cranial base morphology and temporal bone pneumatization in Asian Homo erectus.
AB  - The external morphological features of the temporal bone are used frequently to
      determine taxonomic affinities of fossils of the genus Homo. Temporal bone
      pneumatization has been widely studied in great apes and in early hominids.
      However, this feature is rarely examined in the later hominids, particularly in
      Asian Homo erectus. We provide a comparative morphological and quantitative
      analysis of Asian Homo erectus from the sites of Ngandong, Sambungmacan, and
      Zhoukoudian, and of Neandertals and anatomically modern Homo sapiens in order to
      discuss causes and modalities of temporal bone pneumatization during hominid
      evolution. The evolution of temporal bone pneumatization in the genus Homo is
      more complex than previously described. Indeed, the Zhoukoudian fossils have a
      unique pattern of temporal bone pneumatization, whereas Ngandong and Sambungmacan
      fossils, as well as the Neandertals, more closely resemble the modern human
      pattern. Moreover, these Chinese fossils are characterized by a wide midvault and
      a relatively narrow occipital bone. Our results support the point of view that
      cell development does not play an active role in determining cranial base
      morphology. Instead, pneumatization is related to available space and to temporal
      bone morphology, and its development is related to correlated morphology and the
      relative disposition of the bones and cerebral lobes. Because variation in
      pneumatization is extensive within the same species, the phyletic implications of
      pneumatization are limited in the taxa considered here.

PMID- 16911820
TI  - Failure investigation of soldered stainless steel orthodontic appliances exposed
      to artificial saliva.
AB  - Globally in the field of Dental Technology, soldering continues to be the
      prevailing joining technique for removable orthodontic appliances. The strength
      of the soldered joint, however, is a growing concern to dental technicians since
      the commonly employed silver solder undergoes accelerated corrosion and
      ultimately influences the success of orthodontic appliances intraorally.
      OBJECTIVE: The goal of this in vitro study was to determine the effects of
      exposure to artificial saliva on the mechanical strength of orthodontic silver
      soldered stainless steel joints. METHODS: One hundred (control group n=20; aged
      group n=80) soldered specimens were exposed to varying exposure times in
      Fusayama's artificial saliva. Tensile failure loads of the control and aged
      groups were measured. Failure modes were evaluated by examining the exposed
      surfaces, solder microstructure and the fracture morphology using a combination
      of light microscopy, scanning electron microscopy (SEM) and energy dispersive
      spectroscopy (EDS). RESULTS: A marked decrease in tensile failure load of the
      joints was recorded after exposure to artificial saliva. Selective attack was
      identified on the aged solder surfaces, which was attributed to the micro
      galvanic effect brought about by the preponderance of Cu-rich phases in the
      solder microstructure. The selective attack promoted decohesion at the
      solder/wire interface, thereby reducing the tensile failure load. SIGNIFICANCE:
      This study helped to elucidate that an association between exposure periods and
      microstructure of soldered orthodontic joints exists and that their combined
      effects positively influence the tensile strengths of orthodontic soldered
      joints.

PMID- 16911821
TI  - Influence of fluorescent whitening agent on the fluorescent emission of resin
      composites.
AB  - OBJECTIVES: The objective of this study was to determine the fluorescent emission
      of experimental resin composites after addition of a fluorescent whitening agent
      in varied concentrations. The effects of thermocycling and composition of resin
      matrix on the fluorescent emission were also determined. METHODS: An experimental
      light curing resin matrix was made by mixing Bis-GMA, UDMA and TEGDMA in the
      ratio of 1:1:1 by weight, and silane coated glass filler was added in the ratio
      of 50 wt.% of resin composite. A fluorescent whitening agent [FWA, 1,4-double
      (benzoxazole-group-2-group)naphthalene] was added with the concentration of 0.01
      0.1%. To determine the difference by the resin matrix, two resin composites (60
      wt.% Bis-GMA or UDMA with 40 wt.% TEGDMA) with the same filler content were made,
      and the FWA was added. Five specimens of 2mm in thickness were made for each
      group. Spectral reflectance was measured relative to the illuminant D65 on a
      reflection spectrophotometer. From the spectral reflectance values, the
      difference in reflectance (fluorescence spectra) by the inclusion or exclusion of
      UV component was calculated. After the baseline measurement, thermocycling was
      performed for 500 and 1000 cycles, and the fluorescent emission was measured
      again. RESULTS: The concentration of FWA influenced the fluorescent peak heights
      and areas (p<0.05), but thermocycling up to 1000 cycles did not influence the
      values. Fluorescence peak wavelength was not changed by the resin matrix, but
      peak height and area were influenced by the resin matrix (p<0.05). SIGNIFICANCE:
      FWA added with the concentrations of 0.01 and 0.05% emitted fluorescence, which
      was higher than those from commercial resin composites.

PMID- 16911822
TI  - Penetration coefficients of commercially available and experimental composites
      intended to infiltrate enamel carious lesions.
AB  - OBJECTIVES: Arresting of enamel lesions by infiltration with light curing
      composite resins might be a treatment alternative of future micro-invasive
      dentistry. So far only commercially available adhesives and fissure sealants have
      been used to infiltrate enamel lesions. Since these products have been optimized
      for adhesive purposes, the aim of this study was to develop optimized resins for
      the infiltration of enamel lesions and to measure their physical properties.
      METHODS: The penetration coefficients (PCs) of five adhesives and a fissure
      sealant as well as 66 experimental composite resins were determined. To establish
      the resins' PCs the viscosities, surface tensions, and contact angles to bovine
      enamel were measured. RESULTS: For the commercially available products PCs from
      4.0 to 278.9 cm/s were measured. Four of these materials showed a good
      correlation with penetration depths obtained in a previous study. Experimental
      composites showed PCs from 0.2 to 474.9 cm/s. The addition of ethanol
      significantly increased the PCs due to a decrease of viscosity and contact angle.
      Highest PCs were found for mixtures containing TEGDMA, HEMA and 20% ethanol.
      SIGNIFICANCE: The knowledge about the PC of resin composites seems to be useful
      for the development of new materials optimized to infiltrate enamel lesions.

PMID- 16911824
TI  - Larger than life: Mitochondria and the Bcl-2 family.
AB  - The intrinsic pathway of apoptosis relies on mitochondrial membrane
      permeabilization, with Bcl-2 proteins serving as its master regulators. They form
      a complex network of interactions both within the family and with multiple
      cellular factors outside the family. The understanding of the processes that
      regulate mitochondrial breach, and mechanisms that direct the pro- and anti
      apoptotic functions of Bcl-2 proteins, should assist the development of novel
      anticancer therapies. Thus, it is of no surprise that research in the field is
      gaining momentum. In this review we outline the current concepts on regulatory
      circuits governing mitochondrial rupture and action of Bcl-2 proteins during cell
      death, and how this burgeoning knowledge is being translated into the clinics
      with the hope to combat cancer.

PMID- 16911823
TI  - Decidual activation: abundance and localization of prostaglandin F2alpha receptor
      (FP) mRNA and protein and uterine activation proteins in human decidua at preterm
      birth and term birth.
AB  - OBJECTIVE: To study how the decidua contributes to parturition, we examined
      prostaglandin F(2alpha) concentrations as well as prostaglandin 15-hydroxy
      dehydrogenase, prostaglandin F(2alpha) receptor, matrix metalloproteinases 2 and
      9, oxytocin receptor, prostaglandin-H synthase-2, and the prostaglandin E(2)
      receptor expression in human decidua. MATERIALS AND METHODS: Decidual samples
      were isolated from placentas collected from patients at preterm not in labor
      (PTNIL), preterm labor (PTL), term not in labor (TNIL), and term labor (TL). For
      immunohistochemistry, fresh membranes which included chorion, amnion and decidua
      from term patients were collected. RESULTS: Prostaglandin F(2alpha) receptor mRNA
      was low in all preterm patients and then significantly increased towards term
      (p=0.049). Prostaglandin F(2alpha) receptor protein was identified in the amnion
      epithelium and mesoderm, chorion trophoblasts and decidua by
      immunohistochemistry, and levels were highest at TNIL (p=0.007) as measured by
      western blot. Prostaglandin F(2alpha) levels were higher at PTNIL than TNIL.
      Matrix metalloproteinases 2 and 9 protein and pro-enzyme activities were higher
      at TL than TNIL. There were no significant changes among the groups for any of
      the other factors measured. CONCLUSIONS: These results suggest that the induction
      of Prostaglandin F(2alpha) receptor at term may facilitate the decidua
      contribution to parturition, and its regulation and role should be examined
      further.

PMID- 16911825
TI  - Molecular cloning characterization and expression of porcine immunoreceptor
      SIRPalpha.
AB  - SWC3 is a porcine CD that has been the reference marker of myeloid lineage. It is
      expressed in every myelomonocytic cell from early bone marrow precursors. We have
      identified the molecule recognized by anti-SWC3 antibodies as a member of the
      signal-regulatory proteins (SIRPs)alpha family. Here, we describe the cloning of
      a cDNA coding for a porcine SIRPalpha protein. The sequence is 2470 nucleotides
      long and contains an open reading frame encoding a 507 amino acid sequence. The
      predicted polypeptide was composed of a 30 amino acids putative signal peptide, a
      342 amino acid extracellular region, a 23 amino acid transmembrane segment and a
      112 amino acid cytoplasmic domain. Analysis of the sequence reveals a high degree
      of homology with known SIRPs in other species, being easily identified the three
      extracellular Ig type domains and two cytoplasmic ITIM motifs characteristic of
      this molecule. The gene coding for porcine SIRPalpha has been mapped to porcine
      chromosome 17, in a region syntenic to the human chromosome 20 where SIRP genes
      have been mapped. During the analysis of SIRP gene expression in tissues by RT
      PCR, we noticed the existence of a shorter mRNA, and cloned the corresponding
      cDNA. This coded for a splicing variant of SIRPalpha that lacked the two membrane
      proximal Ig domains. In transfection experiments, we have been able to show that
      anti-SWC3 antibodies recognize both forms of the molecule, mapping the SWC3
      epitopes to the N-terminal IgV type domain.

PMID- 16911826
TI  - Simultaneous EEG-fMRI.
AB  - Acquisition of electroencephalogram (EEG) during functional magnetic resonance
      imaging (fMRI) provides an additional monitoring tool for the analysis of brain
      state fluctuations. The exploration of brain responses following inputs or in the
      context of state changes is crucial for a better understanding of the basic
      principles governing large-scale neuronal dynamics. State-of-the-art techniques
      allow EEG activity-from DC (direct current) up to high frequencies in the gamma
      range-to be acquired simultaneously with fMRI data. In the interleaved mode,
      spiking activities can also be assessed during concurrent fMRI. The utilization
      of fMRI evidence to better constrain solutions of the inverse problem of source
      localization of EEG activity is an exciting possibility. Nonetheless, this
      approach should be applied cautiously since the degree of overlap between
      underlying neuronal activity sources is variable and, for the most part, unknown.
      The ultimate goal is to make joint inferences about the activity, dynamics, and
      functions by exploiting complementary information from multimodal data sets.

PMID- 16911827
TI  - Postnatal environmental or experiential amelioration of neurobehavioral effects
      of perinatal alcohol exposure in rats.
AB  - Fetal alcohol spectrum disorders (FASDs) in children are characterized by life
      long compromises in learning, memory, and adaptive responses. To date, there are
      no clinical remedies for the treatment of global fetal alcohol effects, although
      interventions for specific outcomes are available. Here we review basic research
      in animal models of perinatal alcohol exposure to assess the potential of global
      environmental manipulations to ameliorate the neurobehavioral effects associated
      with FASD. Enhancement of the postnatal environment via neonatal handling,
      environmental enrichment, or rehabilitative or "therapeutic" motor training, can
      improve behavioral performance and ameliorate or even eliminate some deficits in
      perinatal alcohol-exposed rats and mice. While neuroanatomical changes associated
      with the behavioral improvements have been reported in some models, there
      generally appears to be a persistent impairment in neuronal plasticity. Such
      research suggests that it may be possible to manage the postnatal environment or
      experience of children with FASDs to improve function. It is, however, necessary
      to consider the difficulties in translating findings from research in animals to
      the clinic, school or home because sex-, postnatal age- and species-specific
      differences are critical factors in how specific environments may influence brain
      development. Continued study of the potential ameliorative effects of neonatal
      handling, environmental enrichment, and rehabilitative training as "therapies" in
      animal models will remain a valuable source of information for eventually
      devising treatments for children with FASDs.

PMID- 16911828
TI  - In vivo effects of oligodeoxynucleotides containing synthetic immunostimulatory
      motifs in the immune response to swine streptococcic septicemia vaccine in weaned
      piglets.
AB  - The diverse immunostimulatory effects of CpG oligodeoxynucleotides (CpG ODN) have
      been demonstrated extensively in mice and human. Although the immunoadjuvant
      effects of CpG ODN in pigs were also studied in several reports, until now,
      little work has been carried out with regard to their effects on the adaptive
      immune system of newly weaned piglets. In this study, swine streptococcic
      septicemia killed vaccine (SSSK vaccine) was used as antigen, we assessed the in
      vivo immunostimulatory effects of different CpG motifs in newly weaned piglets.
      The proportion of CD4(+), CD8(+) T lymphocytes subpopulations and proliferation
      of peripheral blood mononuclear cells (PBMCs), IFN-gamma and IL-6 in serum, and
      the titre of IgG and IgG2/IgG1 isotype to SSSK vaccine in serum were tested at
      different time-points. The results suggested that, the CD4(+)/CD8(+) ratio
      decreased significantly in weaned piglets inoculated with phosphate buffer saline
      (PBS) alone, however, it was stable in CpG ODN-coinoculated newly weaned piglets.
      IFN-gamma and IL-6 levels, the titres of specific antibodies IgG, IgG2 and
      proliferative responses of CpG ODN-coinjected piglets were all significantly
      higher than those of SSSK vaccine alone or PBS or GpC ODN-coinjected piglets. The
      porcine-specific ODN-induced responses were stronger in animals injected with
      human-specific or mouse-specific CpG ODN. These in vivo data demonstrate for the
      first time that CpG ODN can stimulate adaptive immune system in weaned piglets.

PMID- 16911829
TI  - Molecular cloning of an invertebrate goose-type lysozyme gene from Chlamys
      farreri, and lytic activity of the recombinant protein.
AB  - Lysozyme is a widely distributed hydrolase possessing lytic activity against
      bacterial peptidoglycan, which enables it to protect the host against pathogenic
      infection. In the present study, the cDNA of an invertebrate goose-type lysozyme
      (designated CFLysG) was cloned from Zhikong scallop Chlamys farreri by expressed
      sequence tag (EST) and rapid amplification of cDNA ends (RACE) techniques. The
      full-length cDNA of CFLysG consisted of 829 nucleotides with a canonical
      polyadenylation signal sequence AATAAA and a poly(A) tail, and an open reading
      frame (ORF) of 603 bp encoding a polypeptide of 200 amino acid residues with a
      predicted molecular weight of 21.92 kDa and theoretical isoelectric point of
      7.76. The high similarity of CFLysG with goose-type (g-type) lysozymes in
      vertebrate indicated that CFLysG should be an invertebrate counterpart of g-type
      lysozyme family, which suggested that the origin of g-type lysozyme preceded the
      emergence of urochordates and even preceded the emergence of deuterostomes.
      Similar to most g-type lysozymes, CFLysG possessed all conserved features
      critical for the fundamental structure and function of g-type lysozymes, such as
      three catalytic residues (Glu 82, Asp 97, Asp 108). By Northern blot analysis,
      mRNA transcript of CFLysG was found to be most abundantly expressed in the
      tissues of gills, hepatopancreas and gonad, weakly expressed in the tissues of
      haemocytes and mantle, while undetectable in the adductor muscle. These results
      suggested that CFLysG could possess combined features of both the immune and
      digestive adaptive lysozymes. To gain insight into the in vitro lytic activities
      of CFLysG, the mature peptide coding region was cloned into Pichia pastoris for
      heterogeneous expression. Recombinant CFLysG showed inhibitive effect on the
      growth of both Gram-positive and Gram-negative bacteria with more potent
      activities against Gram-positive bacteria, which indicated the involvement of
      CFLysG in the innate immunity of C. farreri.

PMID- 16911830
TI  - MBL and C1q compete for interaction with human endothelial cells.
AB  - C1q, the recognition molecule of the classical pathway of complement, binds to
      endothelial cells, leading to cell activation. Mannose-binding lectin (MBL), a
      recognition molecule of the lectin pathway, is structurally and functionally
      related to C1q. Therefore, we investigated the interaction of MBL with human
      umbilical vein endothelial cells (HUVEC). C1q and MBL were purified from normal
      human plasma and binding to HUVEC was evaluated by flow cytometry. Cross
      competition experiments were performed using MBL and C1q labeled with
      digoxygenin. MBL, similar to C1q, exhibited a dose-dependent binding to HUVEC
      under calcium-free conditions, suggesting involvement of its collagenous domains.
      Pre-incubation of HUVEC with MBL inhibited the binding of digoxygenin-labeled MBL
      at equimolar concentrations, confirming the specificity of the interaction. Pre
      incubation of HUVEC with MBL inhibited the binding of C1q and vice versa.
      Activation of HUVEC with LPS resulted in increased C1q and MBL binding.
      Stimulation of HUVEC with MBL did not result in a detectable increase in cytokine
      production. Based on these results, we propose that MBL and C1q bind to a shared
      receptor on endothelial cells. Interaction of MBL and C1q with receptors on
      endothelial cells may be involved in inflammatory processes, and in clearance of
      pathogens and apoptotic cells.

PMID- 16911831
TI  - Efficient clearance of opsonised apoptotic cells in the absence of PECAM-1.
AB  - It is now accepted that the recognition and uptake of apoptotic cells by
      phagocytes is a complex process involving a large number of opsonins, receptors
      and ligands, however the relative contribution of all these molecules are still
      debated. Here we examined the role of CD31 (PECAM-1) in the recognition/uptake of
      apoptotic thymocytes by murine bone marrow-derived macrophages (BMDM) in vitro,
      and by resident peritoneal macrophages in vivo. In the absence of serum, CD31
      deficiency, on either the phagocyte or the apoptotic cell, resulted in a
      reduction in the clearance of apoptotic thymocytes, when a high ratio of
      apoptotic cells to macrophages was applied. In the presence of serum however
      there was no discernible contribution of CD31 to the clearance of apoptotic cells
      by bone marrow-derived macrophages, irrespective of the ratio of cells used. In
      vivo peritoneal clearance experiments confirmed that in the presence of soluble
      opsonins CD31 deficiency had no effect on this process. These data suggest that
      the overall role played by CD31 in the ingestion of apoptotic cells is negligible
      and most likely overwhelmed by the effects of serum opsonins, such as complement
      components.

PMID- 16911832
TI  - Hepatitis B virus genotypes and precore/core-promoter mutations in Tunisian
      patients with chronic hepatitis B virus infection.
AB  - OBJECTIVE: The aim of this study was to determine the frequency of genotype and
      precore/core-promoter mutations in chronic hepatitis B virus (HBV) infected
      individuals in Tunisia. METHODS: We studied 164 Tunisian patients (38 HBeAg
      positive and 126 HBeAg-negative) with chronic HBV infection. Genotypes and
      precore/core-promoter mutations were studied using Inno-LiPA and Multiplex-PCR
      and PCR-RFLP methodology. RESULTS: Alanine aminotransferase (ALT) levels were
      higher in HBeAg-positive compared with HBeAg-negative patients (p<0.05). Patients
      with HBeAg-positive chronic hepatitis B were younger than HBeAg-negative chronic
      hepatitis B patients. The 164 genotypes were distributed as follows: 1 genotype A
      (0.6%), 1 genotype B (0.6%), 3 genotype C (1.82%), 139 genotype D (84.75%), and
      20 mixed genotypes (12.2%). In the precore region (41.5%) of the patients had
      exclusively PC mutant and (50.9%) had a mixture of wild-type and variant
      sequences. PC variant was more commonly found in HBeAg-negative patients than in
      HBeAg-positive patients (94.5% vs. 87.8%), respectively. The mutations in the
      core promoter were more common in HBeAg-negative patients (65.4%) than in HbeAg
      positive patients (18.2%). These results indicate that genotype D is predominant
      in Tunisia. Precore mutation occurred invariably among HBeAg-positive and HBeAg
      negative patients, whereas core-promoter mutations were more frequently found in
      HBeAg-negative patients. CONCLUSION: Analysis of these mutants may prove useful
      for clinical evaluation and choice of therapy.

PMID- 16911833
TI  - Endoscopic adenoidectomy in children with submucosal cleft palate.
AB  - OBJECTIVE: To determine the safety and effectiveness of endoscopic partial
      adenoidectomy for the treatment of nasal obstruction in children with submucosal
      cleft palate. METHODS: The medical files of children with symptoms of nasal
      obstruction and submucosal cleft palate who underwent partial transnasal
      endoscopic adenoidectomy from January 1993 to December 2003 were reviewed.
      Operative complications, relief of nasal obstruction, presence of postoperative
      velopharyngeal insufficiency were recorded. RESULTS: There were no operative
      complications. All the children had relief of nasal obstruction. Velopharyngeal
      insufficiency was not observed during the postoperative follow-up. CONCLUSIONS:
      Endoscopic partial adenoidectomy is a safe and effective procedure for the
      treatment of nasal obstruction in children with submucosal cleft palate.

PMID- 16911834
TI  - Chemokine receptors as therapeutic targets in chronic obstructive pulmonary
      disease.
AB  - Chronic obstructive pulmonary disease (COPD) is an increasing global health
      problem for which there are no effective disease-modifying therapies. COPD
      involves chronic inflammation of small airways and lung parenchyma, with the
      recruitment of inflammatory cells. This inflammatory-cell trafficking is
      orchestrated by multiple chemokines, so the blockade of chemokine receptors with
      selective antagonists might be an effective anti-inflammatory strategy in this
      disease. Several studies support the implication of several chemokines and their
      receptors in COPD, including chemokine receptors CXCR2 and CXCR3, with small
      molecule receptor antagonists that are in development being potential anti
      inflammatory therapies. Such a pharmacological strategy would provide a mechanism
      with which to inhibit leukocyte recruitment and, hence, reduce the inflammatory
      profile in COPD, which is currently unaffected by pharmacotherapy.

PMID- 16911835
TI  - Diagnostic tools based on minor groove binder probe technology for rapid
      identification of vaccinal and field strains of canine parvovirus type 2b.
AB  - TaqMan-based diagnostic tests have been developed for the identification of
      canine parvovirus type 2 (CPV-2) strains in the faeces of dogs with diarrhoea,
      including a minor groove binder (MGB) probe assay for identification of type 2
      based vaccines and field strains (types 2a, 2b and 2c). Since type 2b vaccines
      have been licensed recently in Europe, two novel MGB assays were developed for
      discrimination between type 2b vaccines and field strains of CPV. Such assays
      have been found to be highly sensitive, specific and reproducible, allowing for
      simultaneous detection of type 2b vaccinal and field strains present in the same
      specimens. These new assays will help resolution of the diagnostic problems
      related to the detection of a type 2b strain in the faeces of dogs shortly after
      the administration of a type 2b vaccine.

PMID- 16911836
TI  - Multiple hormonal activities of UV filters and comparison of in vivo and in vitro
      estrogenic activity of ethyl-4-aminobenzoate in fish.
AB  - UV filters have been detected in surface water, wastewater and fish, and some of
      them are estrogenic in fish. At present, little is known about their additional
      hormonal activities in different hormonal receptor systems despite their
      increasing use and environmental persistence. Besides estrogenic activity, UV
      filters may have additional activities, both agonistic and antagonistic in
      aquatic organisms. In our study, we investigate a series of UV filters for
      multiple hormonal activities in vitro in human receptor systems and evaluate the
      predictive value of these findings for the activity in fish in vitro and in vivo.
      First we systematically analysed the estrogenic, antiestrogenic, androgenic, and
      antiandrogenic activity of 18 UV filters and one metabolite in vitro at non
      cytotoxic concentrations with recombinant yeast systems carrying either a human
      estrogen (hERalpha) or androgen receptor (hAR). All 19 compounds elicited
      hormonal activities, surprisingly most of them multiple activities. We found 10
      UV-filters having agonistic effects towards the hERalpha. Surprisingly, we
      identified for the first time six UV filters with androgenic activities and many
      of them having pronounced antiestrogenic and antiandrogenic activities. As much
      as 17 compounds inhibited 4,5-dihydrotestosterone activity in the hAR assay,
      while 14 compounds inhibited estradiol activity in the hERalpha assay, indicating
      antiandrogenic and antiestrogenic activity, respectively. In particular, the
      antiandrogenic activities of phenyl- and benzyl salicylate, benzophenone-1 and 
      2, and of 4-hydroxybenzophenone were higher than that of flutamide, a known hAR
      antagonist. In a second series of experiments, we investigated the predictive
      power of the hERalpha assay for aquatic organisms by further investigating the
      estrogenic UV filter ethyl 4-aminobenzoate (Et-PABA) in vitro and in vivo in
      fish. Et-PABA showed estrogenic activity in a recombinant yeast system carrying
      the rainbow trout estrogen receptor (rtERalpha) with higher activity than in the
      hERalpha assay. In addition, Et-PABA induced vitellogenin after 14 days of
      exposure in juvenile fathead minnows at 4394mug/L. Our study shows estrogenic
      activity of this UV filter in fish both in vitro and in vivo. In conjunction with
      in vitro human receptor-based systems our results give a more detailed picture
      about distinct hormonal activities of UV filters occurring in aquatic systems. We
      conclude that receptor-based assays are important for in vitro assessment of UV
      filters prior to or concurrently with in vivo assays, which ultimately provide
      data for the environmental risk assessment of these important personal care
      products.

PMID- 16911838
TI  - The marine secondary metabolites 2,4-dibromophenol and 2,4,6-tribromophenol
      differentially modulate voltage dependent ion currents in neuroendocrine (PC12)
      cells.
AB  - 2,4-Dibromophenol (2,4-DBP) and 2,4,6-tribromophenol (2,4,6-TBP) are marine
      secondary metabolites, with 2,4,6-tribromophenol playing an important role as
      industrially produced flame retardant and pesticide. Both substances disturb
      cellular calcium signals in neuroendocrine cells as previously shown by
      Hassenklover et al. (2006) [Hassenklover, T., Predehl, S., Pilli, J., Ledwolorz,
      J., Assmann, M., Bickmeyer, U., 2006. Bromophenols, both present in marine
      organisms and in industrial flame retardants, disturb cellular Ca(2+) signaling
      in neuroendocrine cells (PC12). Aquat. Toxicol. 76, 37-45]. We investigated
      calcium channel currents in detail and outward membrane currents as potential
      cellular targets of both bromophenols. In this electrophysiological approach, 2,4
      DBP reduced voltage dependent calcium channel currents with a half-maximal
      concentration of 45+/-32 microM (S.D.) and a Hill coefficient of 0.87+/-0.49
      (S.D.). 2,4,6-TBP reduced calcium channel currents with a half-maximal
      concentration of 28+/-19 microM (S.D.) and a Hill coefficient of 0.79+/-0.31
      (S.D.). The major contribution to calcium channel currents was mediated by L-type
      (67%) and N-type channels (30%) in PC12 cells; both bromophenols modulated both
      current types. Whole cell outward currents, mainly carried by potassium ions,
      were reduced by 2,4-DBP with a half-maximal concentration of 41+/-9 microM (S.D.)
      showing a Hill coefficient of 1.71+/-0.31 (S.D.). 2,4,6-TBP showed a weak
      reduction of outward currents at high concentrations of 300 microM. 2,4,6-TBP
      selectively decreased calcium entry via calcium channels as revealed in whole
      cell patch clamp experiments, whereas 2,4-DBP reduced both in- and outward
      currents.

PMID- 16911837
TI  - Impacts of microcystins on the feeding behaviour and energy balance of zebra
      mussels, Dreissena polymorpha: a bioenergetics approach.
AB  - Microcystins are produced by bloom-forming cyanobacteria and pose significant
      health and ecological problems. To investigate the impacts of these biotoxins on
      the physiology of the zebra mussels, Dreissena polymorpha, a series of short-term
      feeding experiments were conducted in the laboratory. We used five microalgal
      diets consisting of single-cell suspensions of the green algae, Chlorella
      vulgaris, the diatom, Asterionella formosa, the cryptophyte, Cryptomonas sp. and
      two strains of the toxic cyanobacterium, Microcystis aeruginosa (strains CCAP
      1450/06 and CCAP 1450/10). A sixth diet was a mixture of the diatom and the CCAP
      1450/10 cyanobacterial strain. The low-toxicity strain CCAP 1450/06 contained 7.4
      microg l(-1) of the MC-LR variant while the very toxic strain CCAP 1450/10
      contained 23.8 microg l(-1) of MC-LR and 82.9 microg l(-1) of MC-LF. A flow
      through system was designed to measure the following feeding parameters:
      clearance, filtration, ingestion and absorption rates. Ultimately the scope for
      growth (SFG) was determined as a net energy balance. We observed that mussels
      cleared the cyanobacterial species containing MC-LF (mean+/-95% confidence
      interval) at a significant lower rate (498+/-82 ml h(-1) g(-1) for the single
      cell suspension and 663+/-100 ml h(-1) g(-1) for the mixture diet) than all of
      the non-toxic species and the cyanobacterium containing MC-LR (all above 1l h(-1)
      g(-1)). The same pattern was observed with all the feeding parameters,
      particularly absorption rates. Furthermore, MC-LF caused an acute irritant
      response manifested by the production of 'pseudodiarrhoea', unusually fluid
      pseudofaeces, rich in mucus and MC-LF-producing Microcystis cells, ejected
      through the pedal gape of the mussels. This overall response therefore
      demonstrates selective rejection of MC-LF-producing cyanobacteria by zebra
      mussels, enhancing the presence of the very toxic MC-LF-producing M. aeruginosa
      in mixed cyanobacterial blooms and in the benthos. Finally, we observed that the
      SFG (mean+/-95% confidence interval) of mussels feeding on M. aeruginosa
      containing MC-LF was significantly lower (34.0+/-18.8 J h(-1) g(-1) for the
      single cell suspension and 83.1+/-53.0 J h(-1) g(-1) for the mixture diet) than
      for mussels ingesting non-toxic diets, except for C. vulgaris (all above 200 J h(
      1)g(-1)). This reveals a sublethal, stressful effect of microcystins
      (particularly MC-LF) on the feeding behaviour and energy balance of the zebra
      mussel.

PMID- 16911839
TI  - Herd-level risk factors for Cryptosporidium infection in dairy-goat kids in
      western France.
AB  - We conducted a cross-sectional study of risk factors for herd-level kid
      positivity for Cryptosporidium parvum oocysts in dairy-goat farms (Deux-Sevres,
      western France). From January to March 2003, faeces from a convenient sample of
      879 5- to 30-day-old goat kids from 60 herds were examined microscopically after
      staining with carbol fuschin. Oocyst shedding was scored semi-quantitatively (0
      to 4+) allowing us to obtain a cumulative score per herd. Standardized
      questionnaires with information about management practices were collected in each
      farm. We found positive kids in 32 of 60 herds (53.3%) and in 142 animals out of
      879 (16.2%). We used logistic regression for two risk-factor model: (1) simple
      positive (case: herd score > or = 1+, at least one positive kid in the herd,
      versus control: herd score=0), (2) strongly positive (case: overall herd score >
      or = 3+ versus control: herd score <3+). Risk factors associated with simple
      positive herds were period of sampling compared to the peak of births (After
      versus Before, OR=4.2, 95% CI 1.2, 15.3) and practice of kid grouping by age or
      weight (Yes versus No, OR=4.4, 95% CI 1.0, 19.1). Risk factors associated with
      strongly positive herds were period of investigation (February/March versus
      January, OR=12.7, 95% CI 2.1, 76.6), exposure to graminaceous plants in forage
      (OR=11.6, 95% CI 1.7, 81.0) and type of ventilation in the goat premises
      (Vertical versus Wind effect, OR=14.7, 95% CI 2.1, 106.1). No important
      association was found between kid-management practices and herd positivity. These
      results suggest a major role of the environment of kids during their first hours
      of life in the adult-goat premises regarding the transmission of C. parvum
      infection.

PMID- 16911840
TI  - Association study of polymorphisms in N-methyl-D-aspartate receptor 2B subunits
      (GRIN2B) gene with Korean alcoholism.
AB  - The N-methyl-D-aspartate (NMDA) receptor 2B gene (GRIN2B) was studied as a
      candidate gene of alcoholism. This study aimed to investigate the association
      between each of the three GRIN2B polymorphisms (rs1806201, rs1805247, and
      rs1805502) and alcoholism. This study included 206 alcoholic patients and 189
      unrelated control subjects of Korean origin. Associations between genotype,
      allele, and haplotype frequencies of the polymorphisms and alcoholism were
      investigated. The genotype frequencies of rs1806201 and the haplotype analysis of
      SNPs in this study show significantly differences between the case and controls.
      These findings suggest new candidate SNPs in GRIN2B for studying the genetic
      susceptibility to alcoholism.

PMID- 16911841
TI  - Survey of dietary habits in obese patients with type 2 diabetes treated with
      either OHA or insulin injections in Japan.
AB  - A questionnaire survey on meal/snack intake and timing in obese patients with
      type 2 diabetes treated with either oral hypoglycemic agents (OHA) or insulin
      injections was performed in order to elucidate their dietary habits, using a
      method independent of the treating physician. The OHA and insulin groups
      recruited from all over Japan showed no differences in any factors except the
      duration of diabetes. Daily calorie intake was not correlated with gender, BMI,
      medication or HbA1c. However, calorie intake was the highest at dinner, followed
      by lunch and breakfast. Only for dinner was the calorie intake significantly
      higher for the OHA group than for the insulin group. Of the patients, 8.6, 4.2
      and 1.3% skipped breakfast, lunch or dinner, respectively. However, there was no
      significant difference in the abstention ratio for the three meals or between the
      two treatment groups. It was remarkable that at least 90% or more reported the
      habitual ingestion of snacks. The snack time ranged from 6:00 a.m. to midnight.
      There was no marked difference in the proportion of patients having snacks
      between the two treatment groups. The outcomes such as deviations in calorie
      intake among the three meals, skipping meals and snacking in this survey may
      reflect the current dietary habits of obese patients with type 2 diabetes,
      especially under medical treatment.

PMID- 16911842
TI  - Epistatic interactions: how strong in disease and evolution?
AB  - When the chimpanzee genome sequence was released, human deleterious alleles
      associated with simple mendelian diseases were observed as wild-type alleles in
      six genes (AIRE, MKKS, MLH1, MYOC, OTC and PRSS1). The absence of recognizable
      phenotypic effects in chimpanzee, contrary to the clinical effect observed in
      humans, is attributed to epistatic interactions (compensation) between
      potentially deleterious and compensatory alleles. In this report we investigate
      the possible evolutionary histories by which substitution of alternative variants
      in these six genes either ameliorates or avoids pathological consequences.

PMID- 16911843
TI  - Transcriptional alterations and chromatin remodeling in polyglutamine diseases.
AB  - Transcriptional dysregulation is now thought to be a common feature of
      polyglutamine disorders, including the spinocerebellar ataxias (SCAs). However,
      the precise causes of transcriptional alterations and how they relate to the
      observed phenotype remain elusive. Transcriptional impairment differs in
      different diseases, possibly reflecting the specific functions of the disease
      causing proteins. The SCA7 gene product, ataxin-7, is a subunit of a
      transcriptional coactivator complex (called STAGA or TFTC) that has histone
      acetyltransferase activity. Studies on the effect of mutant ataxin-7 on STAGA
      function suggest that chromatin remodeling and transcriptional alterations are
      key pathologic events in SCA type 7. These studies could reveal how polyglutamine
      expansions alter the transcriptional regulation of genes required for neuronal
      function.

PMID- 16911844
TI  - What keeps C. elegans regular: the genetics of defecation.
AB  - Caenorhabditis elegans exhibits a repertoire of behaviors that can be studied by
      genetic, anatomical and pharmacological approaches. Defecation is one of the
      simpler behaviors, involving a small number of muscles, a couple of neurons and
      only one neurotransmitter. This simplicity enables the precise characterization
      of the cells and genes required for executing the behavior and has made the
      defecation behavior a powerful model for investigating the genetic basis of
      nervous system function, muscle differentiation, rhythmic behaviors and
      oscillatory calcium signaling, and the metabolic and environmental regulation of
      behavior. Our review highlights how the function of a system even this simple
      results from the integration of many aspects of an organism's biology and
      involves the action of diverse genes.

PMID- 16911845
TI  - Aspergillus genomes: secret sex and the secrets of sex.
AB  - The genomic sequences of three species of Aspergillus, including the model
      organism A. nidulans (which is homothallic: having no differentiated mating
      types, a strain being able to cross with itself), suggest that A. fumigatus and
      A. oryzae, considered to be asexual, might in fact be heterothallic (having two
      differentiated mating types, a strain being able to cross only with strains of
      opposite mating type). The genomic data have implications for the understanding
      of the evolution and the mechanism of sexual reproduction in this genus. We
      propose a model of epigenetic heterothallism to account for the reproductive
      patterns observed in Aspergillus nidulans.

PMID- 16911846
TI  - Molecular epidemiology of meticillin-resistant coagulase-negative staphylococci
      in a Swedish county hospital: evidence of intra- and interhospital clonal spread.
AB  - During a 10-month period in 2003, consecutive routine clinical cultures from
      patients treated in 15 different ward units in a Swedish county hospital were
      screened for the presence of meticillin-resistant coagulase-negative
      staphylococci (CNS). Genetic similarity between isolates was analysed using
      pulsed-field gel electrophoresis (PFGE). The results were compared with multi
      drug-resistant Staphylococcus epidermidis isolated previously at the tertiary
      referral hospital. In total, 428 isolates of CNS were identified, of which 188
      (44%) were meticillin resistant. Three clusters (Groups A, B and C) of S.
      epidermidis, each consisting of more than 10 isolates, with a PFGE-DNA similarity
      of >90% were identified. The strains in Groups A and B (N=15 and N=13,
      respectively), which were generally resistant to gentamicin, co-trimoxazole and
      clindamycin, originated from 24 patients, of whom 21 had been treated in the
      intensive care unit (ICU) before sampling. The third cluster, Group C, involved
      14 isolates from 14 patients. Only two of these patients had stayed at the ICU,
      and all for less than one day. Isolates in Group C were less resistant than those
      in Groups A and B. Isolates belonging to Group A showed an identical PFGE profile
      compared with multi-drug-resistant S. epidermidis isolated from patients at the
      referral hospital. This study demonstrated the persistence and spread of
      meticillin-resistant clones of CNS within the county hospital, especially in the
      ICU, and possible interhospital spread of a multi-drug-resistant clone between
      the county and referral hospitals.

PMID- 16911848
TI  - Sense and the science of childhood immunization: can we achieve more with less?
AB  - The threat of biological terrorism with small pox virus and a global influenza
      pandemic in the face of limited vaccine supply recently stimulated research into
      the evaluation of fractional dose vaccine regimens, with promising immunogenicity
      results. While this approach is not new, it has been less applied to vaccines for
      less sensational but nevertheless, significant killer diseases. This manuscript
      provides an overview of the basics of immunization as it applies to the current
      practice of immunization in children, comments on the untapped avenues for cost
      reduction of vaccine delivery, and the potential for saving more lives with
      currently available resources.

PMID- 16911847
TI  - Hypobaric hypoxia induces oxidative stress in rat brain.
AB  - High altitude exposure results in decreased partial pressure of oxygen and an
      increased formation of reactive oxygen and nitrogen species (RONS), which causes
      oxidative damage to lipids, proteins and DNA. Exposure to high altitude appears
      to decrease the activity and effectiveness of antioxidant enzyme system. The
      antioxidant system is very less in brain tissue and is very much susceptible to
      hypoxic stress. The aim of the present study was to investigate the time
      dependent and region specific changes in cortex, hippocampus and striatum on
      oxidative stress markers on chronic exposure to hypobaric hypoxia. The rats were
      exposed to simulated high altitude equivalent to 6100 m in animal decompression
      chamber for 3 and 7 days. Results indicate an increase in oxidative stress as
      seen by increase in free radical production, nitric oxide level, lipid
      peroxidation and lactate dehydrogenase levels. The magnitude of increase in
      oxidative stress was more in 7 days exposure group as compared to 3 days exposure
      group. The antioxidant defence system such as reduced glutathione (GSH),
      glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase
      (SOD) and reduced/oxidized glutathione (GSH/GSSG) levels were significantly
      decreased in all the three regions. The observation suggests that the hippocampus
      is more susceptible to hypoxia than the cortex and striatum. It may be concluded
      that hypoxia differentially affects the antioxidant status in the cortex,
      hippocampus and striatum.

PMID- 16911849
TI  - Cutaneous delayed-type hypersensitivity (DTH) in a multi-formulation comparator
      trial of the anti-falciparum malaria vaccine candidate RTS,S in rhesus macaques.
AB  - BACKGROUND: Studies are underway to identify more immunogenic formulations of the
      existing anti-falciparum malaria vaccine RTS,S/AS02A. To supplement in vitro
      immunogenicity assays, cutaneous delayed-type hypersensitivity (DTH) may be a
      useful indicator of functional, cell-mediated immunogenicity. METHODS: Adult
      rhesus monkeys were immunized with saline or one of four RTS,S/adjuvant
      formulations: RTS,S/AS01B, RTS,S/AS02A-standard (current formulation), RTS,S/AS05
      or RTS,S/AS06 at 0, 4, and 12 weeks. An additional cohort received RTS,S/AS02A
      accelerated, at 0, 1, and 4 weeks. Six months after completing immunizations,
      five vaccine-relevant antigens (high and low doses) and two controls were
      administered intradermally. DTH reactivity (induration) was measured at 48 and
      72h, and selected sites were biopsied for histological confirmation. RESULTS: In
      comparison with RTS,S/AS02A-standard, RTS,S/AS01B and RTS,S/AS05 each had larger
      mean reactions (induration) at 5 of 10 (p<0.01, at each site) and 1 of 10
      (p<0.05, at the single site) vaccine relevant test sites, respectively.
      Histologically, perivascular mononuclear cell infiltrates, a cardinal feature of
      DTH, were largest in the RTS,S/AS01B monkeys. INTERPRETATION: In DTH testing,
      with histological confirmation, RTS,S/AS01B was immunogenically superior to
      RTS,S/AS02A-standard and two other novel RTS,S formulations. The DTH outcomes
      paralleled conventional in vitro cellular immunogenicity assessments in
      distinguishing among similar RTS,S formulations, even at 6 months after final
      vaccination.

PMID- 16911850
TI  - Moral reasoning as a model for health promotion.
AB  - The paper describes a model of moral reasoning used to guide the conduct of
      health researchers and recommends that this model be applied in health promotion.
      It argues that this model is a more appropriate and sound way of thinking about
      the means and ends of health education, with implications for both research and
      practice. When faced with ethical dilemmas about the most appropriate course of
      action in health research, investigators and bioethicists conduct normative
      analyses to identify good reasons for choosing one option over another. These
      reasons provide the grounds for determining what one should do, and for changing
      past practices in light of new moral considerations. Since the research community
      seems to think that this is a good way to guide and change their own behavior,
      this model of moral reasoning appears to have relevance and potential application
      to the field of health education, which engages in analogous processes of seeking
      to inform and change the behaviors of the lay public. The article sets this
      approach in the context of a humanistic understanding of human motivation and
      presents two case examples to illustrate the process of moral reasoning. The
      humanistic model outlined here helps to explain why health promotion has not made
      much progress in developing effective behavior change programs and it offers a
      more promising prospect for demonstrating success by identifying a broader range
      of relevant outcomes. The paper concludes by recommending that greater attention
      be paid to the ethical dimensions of human agency in order to develop a more
      coherent body of knowledge to advance both research and practice in health
      promotion.

PMID- 16911851
TI  - Axial-wall inclination angle and vertical height interactions in molar full crown
      preparations.
AB  - OBJECTIVE: This study has been designed to evaluate the interaction of axial wall
      heights with inclination angles in full crown tooth preparations. The interaction
      of these parameters was related to the resulting preparation surface area.
      MATERIALS AND METHODS: A right regular pyramid was used to simulate a single
      mandibular molar preparation with known convergence angles and vertical heights.
      Various combinations of these two variables allowed the calculation of surface
      areas with a formula for the area of a pyramid and right triangles through
      trigonometric manipulations. The pyramidal model system had a 9-mm square base
      with vertical heights from 3- to 5-mm and single-side inclination angles from 2
      to 25 degrees. The occlusal surface was a flat, square or rectangular surface and
      was included in the total area. RESULTS: A percentage of surface area lost or
      gained served as the dependent variables. The significance levels were set at
      10.0% or greater magnitude of loss/gain in a surface area compared to the ideal 2
      degree-level. Significant area loss was demonstrated in all alpha-level
      comparisons. The largest change was found in the 5-mm height grouping compared to
      the 3-mm height grouping, -36.6% difference between groups at the 2 degree-level.
      CONCLUSIONS: Axial single-side inclination angles greater than 10 degrees in 3-
      and 4-mm height-molars are detrimental to maximum surface area in full crown
      restorations. The 5-mm axial wall height with < or = 10 degree single wall has
      been shown to maximize the luting agent surface area between restoration and
      tooth structure.

PMID- 16911852
TI  - Upper urinary tract transitional cell carcinoma: recurrence rate after
      percutaneous endoscopic resection.
AB  - OBJECTIVES: To assess oncologic outcomes in patients undergoing percutaneous
      management for upper urinary tract transitional cell carcinoma (UUT-TCC) of the
      renal cavities. METHODS: We performed a retrospective review of data for patients
      who underwent percutaneous conservative surgery for a UUT-TCC between 1989 and
      2005: sex; age at diagnosis; mode of diagnosis; smoking; history of bladder
      cancer; type of surgery; complications; tumour site, size, stage and grade, and
      recurrence and progression. We evaluated recurrence and survival rates. RESULTS:
      Data were analyzed for 24 patients. Median age was 70 yr. The tumour was located
      in the renal pelvis in 11 patients and in the caliceal system in 13 patients.
      Mean tumour size was 1.8 cm (range: 0.8-2.9). Four patients had a history of
      bladder carcinoma. Three patients experienced perioperative blood loss requiring
      transfusion, and one experienced colon wound. Median follow-up was 62 mo. Eight
      (33.3%) patients experienced local recurrence (three in the treated urinary
      tract, one in the contralateral tract, four in the bladder). Five patients
      underwent nephroureterectomy (NUT) during follow-up. Five (20.8%) patients have
      died, four from disease progression and one from cardiovascular causes. The 5
      year disease-specific and tumour-free survival rates were 79.5% and 68%,
      respectively. CONCLUSIONS: Percutaneous management can be recommended as an
      alternative to NUT or ureteroscopy for low-grade or superficial UUT-TCCs
      localised in the renal cavities. These patients require long-term postsurgical
      surveillance. For patients with high-grade or invasive tumours, open NUT remains
      the gold standard.

PMID- 16911853
TI  - Prostate cancer in the Swedish section of ERSPC--evidence for less metastases at
      diagnosis but not for mortality reduction.

PMID- 16911854
TI  - Predicting retroperitoneal histology in postchemotherapy testicular germ cell
      cancer: a model update and multicentre validation with more than 1000 patients.
AB  - OBJECTIVES: Surgical resection of postchemotherapy retroperitoneal lymph nodes is
      often performed in patients with advanced nonseminomatous testicular germ cell
      cancer. We previously developed a model to predict the probability that the lymph
      nodes contain only necrotic or fibrotic (benign) tissue versus mature teratoma
      and viable cancer (tumour) to identify patients who actually need resection. The
      present study used an updated model with new patient data and studied the
      validity of the updated model across various settings. METHODS: We combined data
      of 544 patients from the original model with data of 550 new patients and
      performed a new logistic regression analysis, which included the same six
      predictors: histology of the primary tumour, prechemotherapy serum levels of
      alpha-fetoprotein, human chorionic gonadotropin, lactate dehydrogenase, residual
      mass size measured on computed tomography, and change in mass size. The validity
      of the updated model was studied in individual centres. Calibration of the
      predicted probabilities was assessed graphically and with the Hosmer-Lemeshow
      test. Discrimination was studied with the concordance (c)-statistic. RESULTS: The
      updated model had slightly different, although more precise, regression
      coefficients. Statistically nonsignificant Hosmer-Lemeshow tests confirmed good
      calibration in most centres. The c-statistic for all centres except one exceeded
      0.80. The updated model was valid over the complete range of predicted
      probabilities across a broad spectrum of centres. CONCLUSIONS: This finding gives
      confidence in the applicability of the model to select patients for resection,
      particularly patients with small residual masses and low predicted probabilities
      of benign tissue (i.e., substantial predicted risks of residual tumour).

PMID- 16911855
TI  - Safety culture and accident analysis--a socio-management approach based on
      organizational safety social capital.
AB  - One of the biggest challenges for organizations in today's competitive business
      environment is to create and preserve a self-sustaining safety culture.
      Typically, the key drivers of safety culture in many organizations are
      regulation, audits, safety training, various types of employee exhortations to
      comply with safety norms, etc. However, less evident factors like networking
      relationships and social trust amongst employees, as also extended networking
      relationships and social trust of organizations with external stakeholders like
      government, suppliers, regulators, etc., which constitute the safety social
      capital in the Organization--seem to also influence the sustenance of
      organizational safety culture. Can erosion in safety social capital cause
      deterioration in safety culture and contribute to accidents? If so, how does it
      contribute? As existing accident analysis models do not provide answers to these
      questions, CAMSoC (Curtailing Accidents by Managing Social Capital), an accident
      analysis model, is proposed. As an illustration, five accidents: Bhopal (India),
      Hyatt Regency (USA), Tenerife (Canary Islands), Westray (Canada) and Exxon Valdez
      (USA) have been analyzed using CAMSoC. This limited cross-industry analysis
      provides two key socio-management insights: the biggest source of motivation that
      causes deviant behavior leading to accidents is 'Faulty Value Systems'. The
      second biggest source is 'Enforceable Trust'. From a management control
      perspective, deterioration in safety culture and resultant accidents is more due
      to the 'action controls' rather than explicit 'cultural controls'. Future
      research directions to enhance the model's utility through layering are addressed
      briefly.

PMID- 16911857
TI  - Characterization of chemically modified corncobs and its application in the
      removal of metal ions from aqueous solution.
AB  - The objective of this work was to convert corncobs to activated carbon by low
      temperature chemical treatment for removing copper from wastewater. The
      parameters for developing a new adsorbent i.e. sorption capacity, selectivity,
      regenerability, suspension test, and kinetics were investigated. All studies were
      performed in batch experiments. Removal of copper from aqueous solutions varied
      with the amount of adsorbent, metal ion concentration, agitation time, solution
      pH and the species of copper present. It was found that the effect of temperature
      was very small. The Langmuir model was found to best fit the equilibrium isotherm
      data. Kinetics of copper removal at two different temperatures obeyed Lagergren
      pseudo-first-order equation. Effect of water hardness, other cations (Pb(2+) and
      Zn(2+)) on copper removal was also studied. Experiments with anionic and cationic
      complexes of copper showed that anionic copper species are not removed at all by
      the prepared material. To observe the nature of surface and pore structure
      scanning electron microscope (SEM) images of modified corncobs were used. To
      study the interaction forces between the adsorbent and the metal ion functional
      group analysis with infrared spectroscopy and proximate analysis were carried
      out. In addition, recovery of the metals ion and regeneration of spent adsorbent
      was possible by acidified hydrogen peroxide. Since the uptake capacity of the
      prepared adsorbent is 26mg Cu/g for copper, it can be a potential adsorbent for
      removing and recovering other heavy metal ions from contaminated wastewaters. The
      sorption capacity of the treated corncobs for copper was better than the reported
      capacity of other activated carbons prepared from agricultural sources.

PMID- 16911856
TI  - Flashing liquid jets and two-phase droplet dispersion II. Comparison and
      validation of droplet size and rainout formulations.
AB  - Loss of containment often results in flashing releases of hazardous chemicals
      into the atmosphere. Rainout of these chemicals reduces airborne concentrations,
      but can also lead to extended cloud duration because of re-evaporation of the
      rained-out liquid. Therefore, for hazard assessment one must use models which
      accurately predict both the amount of rainout and its rate of re-evaporation.
      However, the findings of a literature survey reveal weaknesses in the state-of
      the-art for modelling the sub-processes of droplet atomisation, atmospheric
      expansion, two-phase dispersion, rainout, pool formation and re-evaporation. A
      recent joint industry project has implemented recommendations from this survey,
      deriving from scaled water experiments droplet size correlations for conditions
      ranging from negative to high superheat. This experimental programme is reported
      in more detail in a separate companion paper. As a whole these correlations
      describe a tri-linear function of droplet size (expressed as Sauter mean
      diameter) as a function of superheat. This function describes the regimes of non
      flashing, the transition between non-flashing and flashing, and fully flashing.
      The new correlations have been compared with previous correlations recommended by
      the Dutch Yellow Book and CCPS Books. The correlations are validated against
      published experiments including the STEP experiments (flashing propane jets),
      experiments by the Von Karman Institute (flashing R134-A jets), and water and
      butane experiments carried out by Ecole des Mines and INERIS. The rainout
      calculations by the dispersion model have been validated against a subset of the
      CCPS experiments (flashing jets of water, CFC-11, chlorine, cyclohexane,
      monomethylamine).

PMID- 16911858
TI  - Assuring process safety in the transfer of hydrogen cyanide manufacturing
      technology.
AB  - This paper outlines the critical issues to be addressed in the transfer of
      hydrogen cyanide (HCN) manufacturing technology to a licensee. Process safety
      management (PSM) is of critical importance because of the toxicity, flammability
      and reactivity of HCN. The critical issues are based on experience that DuPont
      has gained (1) while safely manufacturing hydrogen cyanide for over 50 years, and
      (2) while DuPont has safely licensed HCN technology to other firms at locations
      around the world. DuPont's HCN experience has been combined with Aker Kvaerner's
      project engineering experience to insure the safe transfer of HCN technology to a
      licensee.

PMID- 16911859
TI  - Nuclear localization of the 20S proteasome subunit in Parkinson's disease.
AB  - Considering the involvement of ubiquitin-proteasome system (UPS) in Parkinson's
      disease (PD), the aim of the present study was to determine the distribution of
      proteasomes in PD brains. Immunohistochemical studies showed localization of 20S
      proteasome in the nuclei of neurons of the putamen and substantia nigra of PD. In
      contrast, no nuclear staining was observed in the same areas of brains of
      controls. Our results suggest that nuclear localization of 20S proteasome seems
      to be associated with the pathogenesis of PD.

PMID- 16911860
TI  - Long-term analysis of feline calicivirus prevalence and viral shedding patterns
      in naturally infected colonies of domestic cats.
AB  - Feline calicivirus (FCV) is a highly infectious respiratory pathogen of domestic
      cats. The prevalence of FCV in the general cat population is high, particularly
      in multi-cat households, largely because many clinically recovered cats remain
      persistently infected carriers. In order to assess how FCV circulates in such
      groups and to assess the contribution that each individual animal makes to the
      epidemiology of the disease, we have carried out the first detailed analysis of
      long-term shedding patterns of FCV in individual cats within naturally infected
      colonies. The prevalence of FCV in each of the groups on individual sampling
      occasions ranged from 0% to 91%, with averages for the individual colonies
      ranging from 6% to 75%. Within each of the colonies, one to three distinct
      strains of FCV were identified. Individual cats showed a spectrum of FCV shedding
      patterns over the sampling period which broadly grouped into three categories:
      those that shed virus relatively consistently, those that shed virus
      intermittently, and those that appeared never to shed virus. This is the first
      report identifying non-shedder cats that appear resistant to FCV infection over
      long periods of time, despite being continually exposed to virus. Such resistance
      appeared to be age related, which may have been immune-mediated, although by
      analogy with other caliciviruses, factors such as host genetic resistance may
      play a role. Given that a proportion of the population appears to be resistant to
      infection, clearly the cohort of cats that consistently shed virus are likely to
      provide an important mechanism whereby infection can be maintained in small
      populations.

PMID- 16911861
TI  - Non-viability of Haemophilus parasuis fur-defective mutants.
AB  - By complementation of an Escherichia coli fur mutant, the Haemophilus parasuis
      fur gene has been isolated from a genomic library of this organism. The H.
      parasuis fur gene is the distal one of a three-gene operon. Two genes placed
      upstream of the H. parasuis fur open-reading frame encode for a hypothetical
      protein and a flavodoxin, respectively. Attempts performed to isolate an H.
      parasuis fur-defective mutant either through manganese-resistance selection or
      exchange markers were unsuccessful. Likewise, anaerobic growth conditions do not
      enable the attainment of H. parasuis fur-defective mutants either. Nevertheless,
      H. parasuis clones carrying a knockout mutation in the chromosomal fur gene by
      insertion of a KmR cassette were obtained when a stable plasmid, containing an
      additional copy of the transcriptional unit to which the fur gene belongs, was
      present. Likewise, the presence of a plasmid in which the H. parasuis fur gene is
      under the control of the Escherichia coli tac promoter allows for the isolation
      of fur::Km mutants of this organism. Nonetheless, no fur-defective mutants may be
      isolated from H. parasuis cells harbouring a stable plasmid in which only the
      single fur gene is contained. These data clearly indicate that H. parasuis cell
      viability requires the presence of a wild-type fur gene.

PMID- 16911862
TI  - Sperm motion characteristics of GarolexMalpura sheep evolved in a semi-arid
      tropical environment through introgression of FecB gene.
AB  - The arid and semi-arid tropical climates of India are endowed with vast diversity
      of non-prolific sheep breeds. The GarolexMalpura sheep has been evolved in a semi
      arid tropical environment by introgression of FecB gene via artificial
      insemination of Malpura ewes using diluted semen of prolific microsheep Garole
      and subsequently multiplied by inter se mating among GarolexMalpura halfbreds.
      The aim of the present study was to identify FecB mutation in sexually mature
      GarolexMalpura rams by forced RFLP-PCR of BMPR-1B gene and evaluate: (i) semen
      production and sperm motion characteristics of GM rams and (ii) influence of age
      and FecB genotype on their semen attributes. Semen was collected during autumn
      season from 12 donor rams by artificial vagina on 8 occasions at weekly interval.
      The overall means of traits which did not differed significantly with age or FecB
      genotyping were volume (0.72 ml), mass motility (4.44), sperm concentration
      (2721.56 x 10(6)ml(-1)), curvilinear velocity (134.51 microm/s), motility
      (81.3%), amplitude of lateral head displacement (6.24 microm), beat frequency
      (44.43 Hz), sperm head elongation (48.9%) and sperm head area (10.01 microm(2)).
      The FecB genotyping had a significant effect (P<0.05) on percent linearity and
      rapid motile sperms, which did not vary significantly with age. Although sperm
      concentration was higher in FecB(BB) and FecB(B+), compared to FecB(++) genotypes
      but the effect was non-significant. The age and FecB genotyping had significant
      effects (P<0.05) on straightness, average path velocity, straight-line velocity
      and percentage of medium or slow motile sperms. It is concluded that
      GarolexMalpura rams with introgressed FecB gene are capable of producing good
      quality semen in a semi-arid tropical climate.

PMID- 16911863
TI  - Comparative postnatal development of spinal, trigeminal and vagal sensory root
      entry zones.
AB  - Somatic and visceral sensory information enters the central nervous system (CNS)
      via root entry zones where sensory axons span an environment consisting of
      Schwann cells in the peripheral nervous system (PNS) and astrocytes and
      oligodendrocytes in the CNS. While the embryonic extension of these sensory axons
      into the CNS has been well-characterized, little is known about the subsequent,
      largely postnatal development of the glial elements of the root entry zones. Here
      we sought to establish a comparative developmental timecourse of the glial
      elements in the postnatal (P0, P3, P7, P14) and adult rat of three root entry
      zones: the spinal nerve dorsal root entry zone, the trigeminal root entry zone,
      and the vagal dorsal root entry zone. We compared entry zone development based on
      the expression of antigens known to be expressed in astrocytes, oligodendrocytes,
      oligodendrocyte precursor cells, Schwann cells, radial glial fibres and the PNS
      extracellular matrix. These studies revealed an unexpected distribution among
      glial cells of several antigens. In particular, antibodies used to label mature
      oligodendrocytes (RIP) transiently labelled immature Schwann cell cytoplasm, and
      a radial glial antigen (recognized by the 3CB2 antibody) initially decreased, and
      then increased in postnatal astrocytes. While all three root entry zones had
      reached morphological and antigenic maturity by P14, the glial elements
      comprising the PNS-CNS interface of cranial root entry zones (the trigeminal root
      entry zone and the vagal dorsal root entry zone) matured earlier than those of
      the spinal nerve dorsal root entry zone.

PMID- 16911864
TI  - Breast specimen lumpectomy orientation: which technique is the best?
AB  - The authors report a cheap, simple, reliable and reproducible technique of breast
      specimen lumpectomy orientation.

PMID- 16911865
TI  - A long-term video-EEG and behavioral follow-up after endothelin-1 induced middle
      cerebral artery occlusion in rats.
AB  - The aim was to test the hypothesis that occlusion of the middle cerebral artery
      (MCA) results in the development of epilepsy in rats. Further, we investigated
      whether lesion volume, hippocampal pathology, early seizures, or severity of
      behavioral impairment is associated with the development and severity of epilepsy
      or interictal spiking. MCA occlusion was induced by intracerebral injection of
      endothelin-1 (ET; 120 pmol). One group of ET-injected rats were followed-up for 6
      months (n = 15) and another for 12 months (n = 20). Sham-operated animals were
      injected with saline (n = 12). Occurrence of early and late seizures was
      monitored by intermittent video-electroencephalography. Sensorimotor function was
      tested with the running wheel and tapered beam-walking tests. Emotional learning
      and memory were assessed with the fear conditioning test and spatial learning and
      memory with the Morris water maze. Finally, brains were processed for histology.
      Only one rat developed late spontaneous seizures (i.e., epilepsy). Epileptiform
      interictal spiking was detected in 9 of 26 animals. Early seizures did not
      predict the development of epilepsy, spiking activity, or severity of behavioral
      impairment. Production of MCA stroke by intracerebral injection of ET was not a
      strong trigger of epileptogenesis in adult rats. Further studies are needed to
      investigate the effect of age, genetic background, and location of ET-injection
      on the development of hyperexcitability and the risk of post-stroke
      epileptogenesis.

PMID- 16911866
TI  - Heterogeneity of vat(E)-carrying plasmids in Enterococcus faecium recovered from
      human and animal sources.
AB  - In this study, quinupristin/dalfopristin (Q/D)-resistant Enterococcus faecium
      isolates (33 from poultry farms and 1 from a human outpatient) with Q/D minimal
      inhibitory concentrations ranging from 4 microg/mL to 32 microg/mL were analysed.
      Polymerase chain reaction detected the presence of vat(E) in all isolates. Using
      pulsed-field gel electrophoresis (PFGE), 14 distinct PFGE patterns were
      identified. The human E. faecium isolate was distinguishable from the 33 farm
      isolates by PFGE. Southern hybridisation localised the vat(E) gene to an 11 kb
      plasmid and resulted in five plasmid hybridisation types. The vat(E)-carrying
      plasmid from the human isolate showed a nearly identical hybridisation pattern to
      a plasmid from a farm isolate. This study showed that the vat(E) gene, conferring
      resistance to Q/D, was carried on different plasmids in a heterogeneous group of
      E. faecium, some of which may be acquired by E. faecium capable of infecting
      humans.

PMID- 16911867
TI  - Antibiotic resistance, integrons and Salmonella genomic island 1 among non
      typhoidal Salmonella serovars in The Netherlands.
AB  - The objective of this study was to investigate the antimicrobial resistance
      patterns, integron characteristics and gene cassettes as well as the presence of
      Salmonella genomic island 1 (SGI1) in non-typhoidal Salmonella (NTS) isolates
      from human and animal origin. Epidemiologically unrelated Dutch NTS strains
      (n=237) originating from food-producing animals and human cases of salmonellosis
      were tested for their susceptibility to 15 antimicrobial agents. Resistance to 14
      of these antimicrobials, including the third-generation cephalosporins, was
      detected. Resistance to sulphonamides, ampicillin, tetracycline, streptomycin,
      trimethoprim and nalidixic acid was common (>/=10% of the strains were
      resistant). Resistance against three or more antimicrobials was observed in 57
      isolates. The same 237 strains were studied for the prevalence of class 1
      integrons, their gene cassettes and the presence of SGI1. Thirty-six isolates
      (15.2%) carried class 1 integrons. These integrons had ten distinct profiles
      based on the size of the integron and restriction fragment length polymorphism
      analysis. Integrons were detected for the first time in serovars Indiana and
      Senftenberg. Multidrug resistance was strongly associated with the presence of
      class 1 integrons in which the aadA2, aadA1, bla(PSE-1), dfrA1, dfrA5, dfrA14 or
      sat genes were present, as determined by nucleotide sequence determination. The
      presence of gene cassettes or combinations of gene cassettes not previously found
      in integrons in Salmonella was observed. SGI1 or its variants (SGI-B, -C and -F)
      were present in 16 isolates belonging to either serovar Typhimurium, Derby or
      Albany. Regardless of whether the isolate was of human or animal origin, the same
      resistance phenotype, integron profile and SGI1 structure could be observed.

PMID- 16911868
TI  - Understanding hematopoietic stem-cell microenvironments.
AB  - The hematopoietic system is the paradigm for adult mammalian stem-cell research.
      Recent advances have improved our understanding of the cellular and molecular
      components of the microenvironment - or niche - that regulates hematopoietic stem
      cells (HSCs). Here, we summarize the molecular and cellular properties of two
      types of niche, namely the osteoblastic and the vascular niche, in homeostatic
      regulation of HSC behavior, including its maintenance, proliferation,
      differentiation, mobilization and homing. We highlight the most recent findings
      and point to an important trend to the study of niche activity in cancers.
      Knowledge of the basic features of the HSC niches, including physical location,
      cell type and various signaling pathways, should provide insights into other stem
      cell systems and benefit clinical applications.

PMID- 16911869
TI  - Cardiac safety of formoterol 12 microg twice daily in patients with chronic
      obstructive pulmonary disease.
AB  - BACKGROUND: Some evidence suggests an increased risk of myocardial infarction and
      dysrhythmia events associated with beta(2)-agonist use in patients with chronic
      obstructive pulmonary disease (COPD). This prospective, multicenter, randomized,
      double-blind, placebo-controlled study compared the cardiac safety of formoterol
      and placebo in patients with COPD. METHODS: After a 3-14-day run-in, 204 patients
      were randomized to receive formoterol 12 microg dry powder inhalation or matching
      placebo twice daily for 8 weeks. Twenty four-hour continuous electrocardiography
      (Holter monitoring) was performed at screening and after 2 and 8 weeks of
      treatment. RESULTS: Only a small number of patients met the predefined criteria
      for a proarrhythmic event (4 formoterol and 2 placebo patients). No patients had
      sustained postbaseline ventricular tachycardia events, postbaseline run of
      ventricular ectopic beats associated with relevant symptoms (e.g. hypotension,
      syncope), or an episode of ventricular flutter or fibrillation. Holter monitoring
      data were variable but showed no clinically meaningful differences between the
      formoterol and placebo groups, respectively, for variables such as (mean+/-SD at
      end of treatment): heart rate (80+/-8.6 vs. 80+/-10.6 bpm), number and rate of
      ventricular premature beats (total 732+/-2685.4 vs. 650+/-2090.6; rate 35+/-131.0
      vs. 30+/-101.3 per h), ventricular tachycardia events (total 0.4+/-1.70 vs. 1.0+/
      9.23; rate 0.02+/-0.082 vs. 0.05+/-0.479 per h), and supraventricular premature
      beats (total 504+/-1844.1 vs. 823+/-2961.8; rate 22+/-80.6 vs. 37+/-129.6 per h).
      Vital signs and electrocardiogram data, including corrected QT intervals (Bazett
      and Fridericia), were similar across treatment groups. The overall adverse event
      experience was similar in the formoterol (n=26 [27%]) and placebo (n=33 [31%])
      groups. The most common adverse events, infections and respiratory events, were
      expected for this patient population. The incidence of cardiac adverse events was
      low (1 formoterol and 4 placebo patients). CONCLUSIONS: The results of this study
      confirm the good cardiovascular safety profile of formoterol in patients with
      COPD.

PMID- 16911871
TI  - Retention, adherence and compliance: important considerations for home- and group
      based resistance training programs for older adults.
AB  - Reports on the efficacy of physical activity intervention trials usually only
      include discussion of the primary outcomes. However, assessing factors such as
      participant retention, adherence and compliance can assist in the accurate
      interpretation of the overall impact of a program in terms of reach and appeal. A
      quasi-randomised trial was carried out to assess and compare retention and
      adherence rates, and compliance with, a twice weekly resistance training program
      provided either individually at home or in a group format. Retirement villages
      (n=6) were assigned to either 'Have A Try' (HAT, home-based) or 'Come Have A Try'
      (CHAT, group-based); both programs included nine strength and two balance
      exercises. The program involved a 20-week Intervention Phase a 24-week
      Maintenance Phase and a 20-week On-going Maintenance Phase. One hundred and
      nineteen participants (mean age 80+/-6 years) were recruited (HAT=38, CHAT=81).
      There was no difference in retention rates at the end of the Intervention Phase,
      but significantly more HAT than CHAT participants had dropped out of the study
      (p<0.01) after the Maintenance Phase and the On-going Maintenance Phase. During
      the Intervention Phase, over half the HAT and CHAT participants completed > or
      =75% of the prescribed activity sessions, but adherence was significantly greater
      in CHAT than HAT during the Maintenance Phase (p<0.01). Participants in CHAT were
      significantly more compliant than HAT participants (p<0.05). Both home- and group
      based formats were successful over the short-term, but, in retirement villages,
      the group program had better adherence and compliance in the longer-term.

PMID- 16911870
TI  - Both integrated and differential regulation of components of the IL-2/IL-2
      receptor system.
AB  - Interleukin-2 was discovered in 1976 as a T-cell growth factor. It was the first
      type I cytokine cloned and the first for which a receptor component was cloned.
      Its importance includes its multiple actions, therapeutic potential, and lessons
      for receptor biology, with three components differentially combining to form
      high, intermediate, and low-affinity receptors. IL-2Ralpha and IL-2Rbeta,
      respectively, are markers for double-negative thymocytes and regulatory T-cells
      versus memory cells. gamma(c), which is shared by six cytokines, is mutated in
      patients with X-linked severe-combined immunodeficiency. We now cover an under
      reviewed area-the regulation of genes encoding IL-2 and IL-2R components, with an
      effort to integrate/explain this knowledge.

PMID- 16911872
TI  - Pedometer accuracy in physical activity assessment of preschool children.
AB  - Yamax SW-200 pedometer validity during unstructured free play was assessed in 13
      preschool children aged 4.1+/-0.6 years using the Children's Activity Rating
      Scale (CARS). Pedometer validity and hip placement reliability were also assessed
      during straight line walking. Data were analysed using regression analyses, 95%
      upper and lower prediction intervals and 95% limits of agreement. The prediction
      intervals for pedometry were wide when using the CARS as a criterion. Limits of
      agreement and prediction intervals for directly observed step counts were also
      wide for pedometers, calling into question their acceptability for use with
      preschoolers. Limitations of employing the CARS direct observation approach as a
      criterion measure of physical activity are also discussed.

PMID- 16911874
TI  - Feasibility of SHARK: a physical activity skill-development program for
      overweight and obese children.
AB  - This study aimed to assess the feasibility of a community-based physical activity
      motor development program, called SHARK, among overweight and obese children.
      Thirteen overweight or obese children aged 8-12 years were recruited to the 10
      week program from the Illawarra region of NSW, Australia. Measures at baseline,
      post-treatment and 9-month follow-up included BMI, motor development, perceived
      competence, objectively measured physical activity and performance of an activity
      of daily living. At post-treatment and follow-up motor development, perceived
      athletic competence and perceived global self-worth had significantly increased.
      Although recorded minutes in moderate-to-vigorous activity significantly declined
      at post-treatment and follow-up, activity daily counts did not. The results
      indicate that community-based activity programs designed to improve the motor
      development and perceived competence of overweight and obese children are
      feasible and may have important and sustainable benefits. However, a larger
      sample size and a comparison group are required to determine whether this
      approach can impact on activity levels and weight status.

PMID- 16911875
TI  - Selected physical capacity norms for Australian football players at the non-elite
      level.
AB  - Australian football is a popular male team sport that consists mainly of
      participants competing at the non-elite level. The main purpose of this study was
      to compare in non-elite Australian football players competing in sub-elite and
      community leagues, selected physical capacities recognised as predictors of lower
      extremity injury in Australian football and/or other sports. Participants were
      143 adult (mean age of 22.2 years) male Western Australian footballers from the
      Western Australian Football League (WAFL) (sub-elite) and the Western Australian
      Amateur Football League (WAAFL) (community). During the 2005 regular playing
      season participants completed a questionnaire and a physical measurement testing
      session. The physical testing session involved the following lower extremity
      measures: generalised joint laxity, leg length discrepancy, presence of Morton's
      toe, foot arch, hamstring flexibility and static balance. Football players from
      the sub-elite and community leagues did not differ significantly in any of the
      physical testing session measures or in the questionnaire items relating to
      injury number in the past 12 months and lower limb preventative device use.
      However, they did differ in some measures with players from the sub-elite league
      significantly more likely to stretch after a match and training, and to have a
      designated stretching leader at their club. While players from the community
      league were significantly more likely to smoke and to participate in sports
      additional to Australian football. Although the selected physical capacities did
      not differ between the sub-elite and community players in this study, future
      research should be aimed at identifying differences for a greater number of
      physical capacities, including skill and endurance, while utilising a larger
      sample.

PMID- 16911876
TI  - Mechanisms of lipid-antigen generation and presentation to T cells.
AB  - The presentation of lipid antigens by CD1 molecules follows precise rules imposed
      by the biochemical nature of lipids. The structures of CD1-lipid complexes are
      elucidating how T-cell receptors interact with hydrophobic antigens. The
      mechanism of lipid uptake and the pathways followed by lipids embedded in the
      cell membrane contribute to the efficient presentation of exogenous and self
      lipids. Lipid presentation is further regulated by the trafficking route of CD1
      proteins and their precise membrane localization within endosomal vesicles.
      Moreover, the generation of immunogenic lipids might require adequate processing,
      which occurs in the presence of lipid-binding proteins, including CD1e. Here, we
      review recent experimental evidence that has revealed new protagonists involved
      in generating immunogenic lipids and has indicated unexpected biological
      mechanisms contributing to immune recognition.

PMID- 16911877
TI  - RecB-dependent mutator phenotype in Neisseria meningitidis strains naturally
      defective in mismatch repair.
AB  - Several invasive serogroup B meningococcal strains phylogenetically related to
      the lineage III (ET-24) exhibited a mutator phenotype as shown by mutagenicity
      assay using rifampicin-resistance as a selection marker. Hypermutation was
      associated to the presence of defective mutL alleles that were genetically
      characterized. Interestingly, the mutator phenotype was suppressed when a non
      functional recB(ET-37) allele, derived from ET-37 meningococcal strains, replaced
      the functional recB allele in a lineage III strain. In contrast, the same gene
      replacement did not affect mutation frequencies in a mismatch repair-proficient
      strain. These results suggested that in MutL-deficient strains spontaneous
      mutations mostly arise from post-replicative DNA synthesis associated to the
      activity of the RecBCD recombination pathway.

PMID- 16911878
TI  - Determination of proteins in infant formula by high-performance liquid
      chromatography-electrospray tandem mass spectrometry.
AB  - To determine the protein content of formula, gel electrophoresis was performed on
      the infant formula samples and the entire protein patterns were analyzed by nano
      high performance liquid chromatography-electrospray tandem mass spectrometry
      (nano-HPLC/ESI/MS/MS). From the commercial infant formula profiled in this study,
      a total of 154 peptides, corresponding to 31 unique proteins were identified by
      nano-HPLC/ESI/MS/MS. Each of the identified peptides was reconfirmed by a strict
      integrated approach using tandem mass spectra. This protein profiling method
      using gel electrophoresis coupled with nano-HPLC/ESI/MS/MS and manual evaluation
      is a sensitive and accurate method for protein identification as well as a
      powerful tool for monitoring various types of food products.

PMID- 16911879
TI  - Comparison of methylene blue-directed biopsies and four-quadrant biopsies in the
      detection of high-grade intraepithelial neoplasia and early cancer in Barrett's
      oesophagus.
AB  - BACKGROUND: Barrett's oesophagus embodies the risk of malignant transformation.
      High-grade intraepithelial neoplasia and early cancer in Barrett's oesophagus are
      often discrete or macroscopically occult lesions and show a patchy distribution
      and therefore, directed biopsies in combination with four-quadrant random
      biopsies are the gold standard for surveillance. AIMS: The aim of this
      prospective study was to compare methylene blue staining and random biopsies in
      patients with early Barrett's neoplasia. PATIENTS AND METHODS: Eighty-six
      patients (mean age 65+/-8 years) with histologically proven but macroscopically
      in evident high-grade intraepithelial neoplasia (n=17) or early cancer in
      Barrett's oesophagus (n=69) on HR-endoscopy with all together 98 lesions, were
      included. In the first step, four-quadrant random biopsies were taken during
      routine endoscopy (group I). In a second step, staining was performed with a 0.5%
      solution of methylene blue with a spray catheter. Biopsies of focal areas with
      decreased stain, heterogeneity of stain or absence stain were taken (group II).
      RESULTS: In 75/86 patients, high-grade intraepithelial neoplasia or early cancer
      in Barrett's oesophagus could be diagnosed in the methylene blue group while 56
      patients were determined in the random biopsies group (P=0.053). High-grade
      intraepithelial neoplasia or early cancer was diagnosed in significantly more
      methylene blue-directed biopsies (80.9% versus 26.4%, P<0.005) and also
      significantly more lesions could be identified in the methylene blue group
      (96/98; 98%) while in the random biopsies group only 58/98 lesions (59%) could be
      localised (P<0.05). When methylene blue was used (1217 versus 562, P<0.0001), the
      average number of specimens taken with methylene blue per patient was about half
      of that with random biopsy (6.5 versus 14.1, P<0.0001). CONCLUSIONS:
      Chromoendoscopy with methylene blue diagnosed significantly more patients and
      lesions with intraepithelial neoplasia or early cancer in Barrett's oesophagus
      compared to random biopsies. In addition, significantly less biopsies were needed
      with methylene blue compared to random biopsies. The use of methylene blue
      directed biopsies appears to improve the detection of intraepithelial neoplasia
      and early cancer in Barrett's oesophagus.

PMID- 16911880
TI  - Cultural safety and maternity care for Aboriginal and Torres Strait Islander
      Australians.
AB  - PURPOSE: To discuss cultural safety and critique the provision of culturally
      appropriate maternity services to remote Aboriginal and Torres Strait Islander
      women in Australia. PROCEDURE: The literature and policies around 'culture' and
      'cultural safety' are discussed and applied to the provision of maternity
      services to Aboriginal and Torres Strait Islander women in remote areas of
      Australia. FINDINGS: The current provision of maternity services to Aboriginal
      and Torres Strait Islander women, particularly those living in remote Australia,
      appears largely inadequate. The provision of culturally safe maternity care
      requires health system reform at all levels including: the individual
      practitioner response; the educational preparation of practitioners; the delivery
      of maternity services and the development of policy at local, state and national
      level. This paper considers the changes that can be made from the individual
      practitioner through to the design and implementation of maternity services.
      PRINCIPAL CONCLUSIONS: Cultural safety provides a useful framework to improve the
      delivery of maternity services to remote Aboriginal and Torres Strait Islander
      women and their families.

PMID- 16911881
TI  - To assist or not to assist: the legal liability of midwives acting as good
      Samaritans.
AB  - At common law no legal duty exists to rescue. This article examines the common
      law position and whether NSW case of Lowns v Woods 1996 ATR 81-376 creates a new
      duty to rescue. Recent legislation in some states provides protection from
      litigation to those who assist in emergencies providing they act in good faith
      and without gross negligence. The implications for midwives who act as good
      Samaritans are discussed.

PMID- 16911882
TI  - Clinical assessment of vertical dimension. 1972.

PMID- 16911883
TI  - Repair of a milled cantilevered implant overdenture bar: a clinical report.
AB  - This clinical report of a fractured cantilevered substructure bar describes an
      alternative treatment to the proposed refabrication of the substructure bar and
      overdenture prosthesis. This report outlines the clinical and laboratory
      procedures to repair the fractured bar, eliminating the time and expense of
      fabricating a new bar and prosthesis.

PMID- 16911884
TI  - Dental implant-assisted prosthetic rehabilitation of a patient with a bilateral
      maxillectomy defect secondary to mucormycosis.
AB  - Prosthodontic rehabilitation of patients with bimaxillary resection involving the
      maxillae, hard and soft palates, and paranasal sinuses presents a significant
      challenge in restoring speech, deglutition, mastication, and respiration. This
      clinical report describes the prosthodontic management of a young girl treated
      for leukemia who required a bilateral maxillectomy secondary to mucormycosis.
      Distraction osteogenesis, bone grafts, osseointegrated implants, and magnet
      attachments were used to provide retention, support, and stability of a large
      definitive obturator.

PMID- 16911885
TI  - Use of CAD/CAM technology to fabricate a removable partial denture framework.
AB  - This article reports on the first patient-fitted chromium cobalt removable
      partial denture framework produced by computer-assisted design, computer-assisted
      manufacture and rapid prototype technologies. Once the dental cast was scanned,
      virtual surveying and design of the framework on a 3-dimensional computer model
      was accomplished. A rapid prototype machine was used for direct fabrication of
      the alloy framework. Traditional finishing techniques were applied, the framework
      was assessed by a clinician in a conventional manner, fitted to the patient, and
      judged to be satisfactory by both the patient and clinician.

PMID- 16911886
TI  - Combination fixed and removable prostheses using a CoCr alloy: a clinical report.
AB  - It is now possible to provide combination fixed/removable prosthetic restorations
      using only 1 dental alloy, such as CoCr, a nonprecious alloy. This alloy offers
      clinical performance and demonstrated corrosion resistance. This clinical report
      demonstrates use of a single CoCr alloy for metal-ceramic fixed partial dentures
      in conjunction with a mandibular removable partial denture.

PMID- 16911887
TI  - Retention of zirconium oxide ceramic crowns with three types of cement.
AB  - STATEMENT OF PROBLEM: Information about the retentive strength of luting agents
      for zirconium oxide-based crowns is limited. It is unknown if this type of high
      strength ceramic restoration requires adhesive cementation to enhance retention.
      PURPOSE: The purpose of this in vitro study was to determine the ability of
      selected luting agents to retain a representative zirconium oxide ceramic crown
      under clinically simulated conditions. MATERIAL AND METHODS: Recently extracted
      human molars were prepared with a flat occlusal surface, 20-degree taper, and
      approximately 4-mm axial length. The axial and occlusal surface areas were
      determined, and specimens were distributed equally by total surface area into 3
      cementation groups (n=12). Zirconium oxide ceramic copings (Procera AllZirkon)
      with an occlusal bar to facilitate removal were fabricated using computer-aided
      design/computer-assisted manufacturing (CAD/CAM) technology. All copings were
      airborne-particle abraded with 50-mum Al(2)O(3) and then cleaned in an ultrasonic
      bath with isopropyl alcohol. Provisional cement was removed from the prepared
      teeth, followed by a pumice prophy. After trial insertion, the copings were
      cleaned with phosphoric acid, rinsed, dried, and dehydrated with isopropyl
      alcohol. They were then cemented with a seating force of 10 kg per tooth, using
      either a composite resin cement with adhesive agent (Panavia F 2.0 and ED Primer
      A & B [PAN]), a resin-modified glass ionomer cement (Rely X Luting [RXL]), or a
      self-adhesive modified composite resin (Rely X Unicem [RXU]). The cemented
      copings were thermal cycled at 5 degrees C and 55 degrees C for 5000 cycles with
      a 15 second dwell time, and then removed along the path of insertion using a
      universal testing machine at 0.5 mm/min. The removal force was recorded, and the
      stress of dislodgement was calculated using the surface area of each preparation.
      A 1-way analysis of variance was used to analyze the data (alpha=.05). The nature
      of failure was also recorded. RESULTS: Mean dislodgement stresses were 5.1, 6.1,
      and 5.0 MPa for PAN, RXL, and RXU, respectively. The 1-way analysis of variance
      revealed no differences in mean crown removal stress among the 3 cementation
      groups. The predominant mode of failure was cement remaining principally on the
      zirconium oxide copings in 46% of the specimens, followed by cement found on the
      tooth in 25.7% of the specimens. CONCLUSIONS: Within the limitations of this
      study, the 3 luting agents, with mean removal stresses ranging from 5.0 to 6.1
      MPa were not significantly different. The use of a composite resin cement with a
      bonding agent did not yield higher coping retention compared to the other 2
      cements tested.

PMID- 16911888
TI  - Influence of light-activated and auto- and dual-polymerizing adhesive systems on
      bond strength of indirect composite resin to dentin.
AB  - STATEMENT OF PROBLEM: Clinicians must be aware of the bonding effectiveness of
      auto- and dual- polymerizing adhesive systems before choosing the material and
      technique of cementing inlay/onlays to dentin. An inadequate choice may
      compromise the success of indirect restorations. PURPOSE: This study compared the
      microtensile bond strength (MTBS) of indirect composite resin bonded to dentin by
      light-activated, autopolymerizing, and dual-polymerizing adhesive systems.
      MATERIAL AND METHODS: Occlusal dentin surfaces of 36 human third molars were
      exposed and flattened. Teeth were assigned to 1 of the following 6 groups (n=6)
      of adhesive luting systems: 2 dual-polymerizing systems (Scotchbond Multipurpose
      Plus/Rely X [SBMP] and Prime & Bond NT Dual Cure/Enforce [PBDC]); 1
      autopolymerizing system (ED Primer/Panavia F [EDP]); and 3 light-activated
      systems (control groups) (Adper Single Bond/Rely X [SB], Prime & Bond NT/Enforce
      [PB], and Clearfil SE Bond/Panavia F [CF]). The restorative materials were
      applied according to manufacturer's directions. A 2-mm-thick prepolymerized
      composite resin (Clearfil APX) disc was cemented with the resin cements on the
      bonded dentin. Teeth were stored in water at 37 degrees C for 24 hours.
      Afterwards, teeth were sectioned both mesial-distally and buccal-lingually to
      obtain multiple bonded beam specimens with 0.8 mm(2) of cross-sectional area.
      Each specimen was tested in tension at a crosshead speed of 0.5 mm/min until
      failure. Data (MPa) were analyzed by 1-way analysis of variance and the Tukey
      post hoc test (alpha=.05). Failure patterns of tested specimens were analyzed
      using scanning electron microscopy. RESULTS: Mean MTBS values (MPa) for
      experimental groups were as follows: SBMP, 32.89 +/- 3.26(a); SB, 26.74 +/-
      7.45(ab); PB, 26.11 +/- 4.48(ab); CF, 25.30 +/- 6.42(ab); EDP, 16.82 +/-
      5.53(bc); PBDC, 11.20 +/- 5.89(c) (P<.001). Groups with similar lowercase letters
      were not significantly different. Failure pattern of fractured specimens varied
      according to the polymerization mode. CONCLUSION: The autopolymerizing system and
      one of the dual-polymerizing systems were as effective as the light-activated
      systems in bonding indirect composite restorations to dentin.

PMID- 16911889
TI  - The effects of porcelain polishing systems on the color and surface texture of
      feldspathic porcelain.
AB  - STATEMENT OF PROBLEM: After the adjustment of glazed porcelain surfaces, the
      surfaces are roughened and must be reglazed or polished with different porcelain
      polishing systems to improve the esthetic appearance and strength of the
      porcelain restorations. PURPOSE: The purpose of this in vitro study was to
      compare the effect of different porcelain polishing methods on the color and
      surface texture of a feldspathic ceramic. MATERIAL AND METHODS: Ninety porcelain
      (Vitadur Alpha) discs (10 x 2 mm) were fabricated in a silicone mold and divided
      into 9 groups (n=10). A medium-grit diamond rotary cutting instrument was used to
      remove the glaze layer, and then the surface was polished using 1 of the 4
      following polishing systems or a combination thereof: polishing paste (Ultra II),
      polishing stick (Diamond Stick), polishing wheel (CeraMaster), or an adjustment
      kit (Porcelain Adjustment Kit). No surface treatments were applied to the control
      group. Color measurements were made using a colorimeter (Minolta CR-321
      ChromaMeter) according to the CIE L( *)a( *)b( *) color system. Color differences
      (DeltaE) between the control group and experimental groups were calculated. The
      acceptable level was chosen as 3.3 DeltaE units. Then the surface roughness (Ra)
      (microm) of the same specimens was evaluated using a profilometer. The data were
      statistically analyzed by 1-way analysis of variance and Tukey HSD tests
      (alpha=.05). To evaluate the effects of the polishing systems on the ceramic
      surfaces at a microscopic level, an additional 9 feldspathic ceramic specimens
      were prepared and polished to represent each of the 9 groups. These specimens
      were examined under a scanning electron microscope (SEM). RESULTS: Polishing
      techniques significantly affected the color of the feldspathic ceramic (P<.001).
      The DeltaE values ranged from 1.03 to 3.36. No significant differences were found
      within the adjustment kit groups or within the polishing wheel groups. All
      specimens polished with the various techniques showed significantly different Ra
      values than the control specimens (P<.001), except for the groups polished using
      the adjustment kit. The highest Ra and DeltaE values were obtained with the use
      of polishing paste and polishing stick alone (P<.001). The SEM observations
      demonstrated that the polishing techniques affected the smoothness of the
      porcelain surface. CONCLUSIONS: The evaluation of the polishing techniques showed
      that the use of an adjustment kit alone or preceding polishing paste or polishing
      stick application created surfaces as smooth as glazed specimens. The use of
      polishing paste alone did not improve the smoothness of the porcelain surface.
      The color differences of all groups were found to be at the acceptable level.

PMID- 16911890
TI  - A surgical guide for dental implant placement in edentulous posterior regions.
AB  - Proper implant placement is crucial for successful implant-supported
      restorations. This article describes a simple technique for fabricating a vacuum
      formed surgical guide to assist in dental implant placement in edentulous
      posterior regions.

PMID- 16911891
TI  - Application of interim fixed reference points to maintain the occlusal vertical
      dimension: a technique for immediate loading protocols in the edentulous
      mandible.
AB  - This article describes a technique for the clinical insertion and use of
      specially designed screws as fixed intraoral reference and attachment points in
      implant dentistry. After insertion, these screws serve to stabilize radiographic
      and surgical templates in the completely edentulous patient. This approach
      provides the advantage of guiding maintenance of the correct occlusal vertical
      dimension and ensuring accuracy and stability during subsequent phases of
      treatment.

PMID- 16911892
TI  - Composite resin root coping with a keeper for magnetic attachment for replacing
      the missing coronal portion of a removable partial denture abutment.
AB  - Numerous methods for replacing missing removable partial denture abutments have
      been introduced, however, most of them are time consuming and require several
      visits to complete the procedure. Since magnetic attachments can provide support
      and bracing as well as retention for overdenture abutments, the remaining tooth
      root structure can be used to support the coping with the keeper. Through the use
      of composite resin and adhesive material, improved retention of the keeper to the
      root may be achieved, along with improved esthetics. This article describes a
      method for replacing the missing abutment of a removable partial denture with a
      magnetic attachment, and a composite resin coping with a keeper.

PMID- 16911893
TI  - A solid bar splint for open-tray implant impression technique.

PMID- 16911894
TI  - A functional impression technique for capturing the superior position of the soft
      palate.

PMID- 16911895
TI  - Epileptic syndromes in infancy and early childhood - evidence-based taxonomy and
      its implications in the ILAE Classification. Proceedings of the International
      Symposium on Epileptic Syndromes in Infancy and Early Childhood held at the 8th
      Annual Meeting of the Infantile Seizure Society. April 29-May 1, 2005. Tokyo,
      Japan.

PMID- 16911896
TI  - In praise of integrated health.

PMID- 16911897
TI  - A Phase II study of St. John's Wort for smoking cessation.
AB  - OBJECTIVES: To examine the feasibility and efficacy of St. John's Wort (SJW) for
      smoking cessation. DESIGN: This one-arm Phase II study utilized an exact two
      stage group sequential design with a 1-week run-in period between the start of
      SJW treatment and the designated quit date. A total of 37 smokers (ages 18-65
      years, smoking > or = 10 cigarettes/day) were started on SJW. Thirteen failed to
      make a verified quit attempt on the predesignated date and were taken off study
      resulting in 24 evaluable subjects. SETTING: Smokers completed clinic visits at a
      cancer center with interval telephone calls and mailings. INTERVENTION:
      Standardized SJW, 450 mg capsules taken orally twice daily along with cessation
      counseling messages. MAIN OUTCOME MEASURES: Subjects completed validated surveys
      and a focused physical examination at baseline. Evaluable subjects were defined
      as those subjects who made a confirmed quit attempt on their "quit date" 1 week
      following initiation of SJW. Smoking status was determined through self-report
      and bioverification using carbon monoxide (CO) testing. RESULTS: Among evaluable
      subjects, the 12-week quit rate was 37.5% (9/24). Quitters had no significant
      change in weight from baseline to 12-weeks cessation. Use of SJW was generally
      well tolerated. CONCLUSIONS: Based upon these results (which suggest that SJW may
      be effective in maintaining smoking cessation) and the high compliance and few
      AEs, we conclude that SJW demonstrates feasibility for use in smoking cessation.
      If SJW proves to be effective in larger controlled studies, it could represent a
      less expensive, more readily accessible and well-tolerated agent to promote
      tobacco cessation.

PMID- 16911898
TI  - Alternatives to hormone replacement therapy: a multi-method study of women's
      experiences.
AB  - OBJECTIVE: To explore women's decision-making regarding use of complementary and
      alternative medicines (CAM) during menopause. METHODS: Qualitative interviews
      were conducted with 20 women who were currently or had previously used hormone
      replacement therapy (HRT), including questions about their experiences with
      alternatives to HRT. This was followed by a non-random questionnaire survey of
      285 demographically representative Canadian women aged 45-65 who were current or
      former HRT users. RESULTS: Fifty-seven percent (57%, n = 162) of women reported
      either having used or considered a CAM approach for menopause. Women who had
      tried or considered CAM were significantly younger (mean age = 54.9 years versus
      56.8 years; t(280) = 3.4, p < .05) and reported experiencing worse menopause
      specific symptoms than those who had not, and these women also reported a worse
      experience of menopause overall. CONCLUSION: : A majority of menopausal women in
      the current study considered or tried CAM alternatives to HRT.

PMID- 16911899
TI  - Use of complementary and alternative medicine in HIV-infected subjects.
AB  - OBJECTIVES: To compare the characteristics of HIV-infected subjects who had ever
      used with those who had never used Complementary and Alternative Medicine (CAM).
      DESIGN: The European Level Epidemiology of Complementary Therapies in HIV project
      (ELECTHIV 2), a case-control study, was conducted in seven European countries.
      All HIV-infected subjects who consecutively attended the offices of the
      collaborating organizations were eligible for this study. Information was
      obtained from self-administered, anonymous questionnaires. SETTING: A total of
      1066 subjects entered the study: 632 were CAM users and 434 had never used CAM.
      RESULTS: CAM use was more common among females than males (odds ratio (OR) 1.6;
      95% confidence interval (CI) 1.2-2.2) and in more educated subjects. CAM use was
      less common among subjects taking highly active antiretroviral therapy (HAART)
      (OR 0.5; 95% CI 0.3-0.8), but was more common in outpatients who reported HAART
      related side effects (specifically neuropathy). CONCLUSION: This study indicates
      that CAM use in HIV-infected subjects is related to female gender, higher levels
      of education and longer duration of HIV infection.

PMID- 16911900
TI  - Development of the simplified Tai Chi exercise program (STEP) for frail older
      adults.
AB  - OBJECTIVE: To develop a simplified Tai Chi exercise program for frail older
      adults. DESIGN: For phase I, using a focus group, 40 frail Taiwanese older adults
      were interviewed to explore their viewpoints on Tai Chi and have been reported
      elsewhere. This paper emphasized on the phase II of the study in which the older
      adults' perspectives were validated by 10 experts using an evaluation survey.
      SETTING: Long-term care facilities. RESULTS: The newly developed simplified Tai
      Chi exercise program (STEP) included three stages-(1) warm-up: comprised nine
      exercises specifically designed to loosen up the body from head to toe; (2) Tai
      Chi movements: encompassed 12 easy-to-learn and easy-to-perform movements; (3)
      cool-down: included three activities to cease the chi and rest the body.
      CONCLUSIONS: The STEP should be further evaluated for its effectiveness in
      enhancing the relative well being and quality of life of frail older adults and
      its applicability as a floor activity in long-term care facilities.

PMID- 16911901
TI  - Gender differences among medical students in attitudes to learning about
      complementary and alternative medicine.
AB  - OBJECTIVES: To explore gender differences in attitudes to CAM among Year 1, 2 and
      3 medical students. DESIGN: Survey; seven-item self-administered questionnaire.
      SETTING: Plenary lectures at the start of semester 2 of the academic year at the
      University of Birmingham Medical School. RESULTS: 35.6% of 662 students were male
      and 64.4% female. Females were more likely than males to feel CAM has an
      important role in healthcare (p < 0.001). This difference increased through the
      medical course (p < 0.05). Females gave a more positive rating than males to the
      use of five therapies in healthcare (p < 001). Females were more positive than
      males about learning the theory (p < 0.001) and practice (p < 0.001) of CAM and a
      greater amount of CAM curriculum time (p < 0.001). CONCLUSIONS: If CAM teaching
      is optional females may be more likely to choose it. An unexpected consequence of
      more women than men entering medical school may be a positive impact on the
      development of integrated medicine.

PMID- 16911902
TI  - An infrared radiation study of the biophysical characteristics of traditional
      moxibustion.
AB  - OBJECTIVES: Moxibustion has been a part of acupuncture practice for thousands of
      years. Traditionally, it includes direct moxibustion, in which moxa sticks are
      burned at acupuncture points on the skin, and indirect moxibustion, in which
      monkshood cakes or ginger or garlic slices are used to insulate the skin from
      burning moxa cones. Recently randomised clinical trials and clinical observations
      suggest that moxibustion can enhance physiological and immune functions, but
      there has been little investigation of the scientific basis of these traditional
      techniques. The present study compared the infrared radiation caused by these
      techniques to that of non-specific controls and to that of the human body surface
      at an acupuncture point. METHODS: A highly sensitive, infrared-spectrum detection
      device was used to compare the spectra of traditional moxibustion materials (n =
      4/group) with those of control materials (n = 4/group) and to the spectrum at the
      surface of an acupuncture point LI 4 (Hegu) in healthy volunteers (n = 7).
      RESULTS: The infrared radiation intensity produced by a traditional moxa stick
      was 43300.41 mV, with a peak on the infrared spectrum of 3.5 microm, while the
      respective radiation intensities of two controls, a smokeless moxa stick and a
      555 cigarette, were 31.15 mV and 37.03 mV with peaks of 7 microm and 3.5 microm.
      The infrared radiation intensities of the three traditional media of indirect
      moxibustion, monkshood cake, ginger slices and garlic slices, were 520.27 mV,
      594.79 mV and 681.87 mV, respectively, all with peaks around 7.5 microm and
      similar spectra. In contrast, the infrared radiation intensities of slices of
      cucumber and carrot, used as control media for indirect moxibustion, were 274.47
      mV and 50.53 mV, respectively, substantially different from those of the
      traditional media. Infrared radiation at LI 4 (Hegu) was 20.40 mV, and peaked on
      the infrared spectrum at about 7.5 microm. The experiment showed that the thermal
      action of the traditional moxa stick was more potent than that of indirect
      moxibustion and its radiation peak was different from that at the acupuncture
      point on the human body. In contrast, the thermal action of traditional indirect
      moxibustion was modest and its radiation peak matched that at the acupuncture
      point. CONCLUSION: Direct moxibustion with a traditional moxa stick may produce
      its potent therapeutic effects by thermal action, while traditional indirect
      moxibustion may act by producing modest thermal action and a sympathetic
      vibration at the skin surface. Non-traditional thermal materials and media may
      not be suitable substitutes for traditional materials. The data provide a
      scientific, biophysical rationale for traditional moxibustion.

PMID- 16911903
TI  - Evaluating complementary and alternative therapy services in primary and
      community care settings: a review of 25 service evaluations.
AB  - OBJECTIVES: To review evaluations of primary and community care complementary
      therapy services. To explore the impact evaluation reports may have had on
      funding decisions taken by NHS commissioners. DESIGN: We collected 32 reports for
      25 services, principally in England. Reports were analysed for content using the
      structure-process-outcome model. Modified BESTCAM guidelines, which came out of a
      Delphi consensus exercise rating the ability of reports to address commissioners'
      priorities, were used to address the second objective. RESULTS: Most commonly,
      evaluators carried out data extraction of referral forms (10), costings of the
      service (9), patient satisfaction questionnaires (9) and patient health status
      questionnaires (8). Five service evaluations addressed NHS cost pressures, with
      another carrying out a cost effectiveness assessment with QALY. CONCLUSION:
      Addressing commissioners' priorities (e.g. GP consultations rates, prescription
      rates, secondary care referrals) in complementary therapy service evaluations may
      bolster chances of securing funding, but are unlikely to be enough on their own.

PMID- 16911904
TI  - Optimizing telephone-based population sampling--a reply.

PMID- 16911905
TI  - Selecting patients for discussion of the ICD as primary prevention for sudden
      death in heart failure.
AB  - This clinical perspective addresses the practical aspects of the decision to
      implant an implantable cardioverter-defibrillator (ICD) for primary prevention of
      sudden death in patients with symptomatic heart failure and reduced left
      ventricular ejection fraction, based on a distillation of recent trial
      experience. Potentially eligible patients are selected on the basis of left
      ventricular ejection fraction < 30% to 35% and anticipated survival with good
      functional capacity beyond 1 year. Communication with these patients focuses on a
      horizon of 5 years, during which for every 100 patients receiving devices,
      approximately 30 patients are predicted to die with or without an ICD, while 7 to
      8 lives may be saved with the ICD. These estimates are presented in the context
      of adverse events, including unnecessary shocks, and the possibility that
      circumstances may arise for which the defibrillator may be inactivated to allow
      natural death.

PMID- 16911906
TI  - Patient selection for primary prevention ICDs--are eps shocking patients into
      consent?

PMID- 16911907
TI  - Ancient Egyptian medicine and the concept of heart failure.
AB  - BACKGROUND: The cardiac glosses of the Ebers papyrus comprise the concepts and
      notions of the Egyptian physicians about the heart and its diseases. We sought to
      analyze some of the cardiac glosses of the Ebers papyrus, focusing on those which
      may describe early concepts of the syndrome of heart failure. METHODS AND
      RESULTS: Review of Joachim's German translation and both Bryan's and
      Ghalioungui's English translations of the Ebers papyrus. One clinical scenario
      describes patients with "weakness of the heart" or "cardiac dysfunction:" "His
      heart is bored," "The heart weakens," "This means that the heart does not speak
      or that the vessels of the heart are dumb. Its information under your hands
      normally appears because of the air with which they are filled is missing...."
      Debility that has arisen in the heart." The other clinical scenario supplies
      information about patients with heart failure and "fluid retention" or
      "congestion": "His heart is flooded. This is the liquid of the mouth. His body
      parts are all together weak"..."His heart is over flooded...." CONCLUSION:
      Whether or not Egyptian medicine and the contents of the papyri paved the way for
      future knowledge, the clinical scenarios included in the Ebers papyrus may
      represent one of the earliest documented observations of the syndrome of heart
      failure.

PMID- 16911908
TI  - Clinical characteristics of 304 kindreds evaluated for familial dilated
      cardiomyopathy.
AB  - BACKGROUND: Familial dilated cardiomyopathy (FDC) is dilated cardiomyopathy of
      unknown cause occurring in 2 or more closely related family members. METHODS AND
      RESULTS: Members of 304 families suspected to have FDC were evaluated by family
      history (FH) and medical record review and were categorized as affected with
      idiopathic dilated cardiomyopathy (IDC), unaffected, unknown, or no data.
      Pedigrees were categorized with confirmed FDC, probable FDC, possible FDC or IDC
      based on strength of evidence. Of the 304 pedigrees, 125 were categorized as
      confirmed FDC, 48 were probable FDC, 72 were possible FDC, and 59 had sporadic,
      nonfamilial IDC. Numbers of living first- and second-degree family members, and
      median number of relatives available for FH was greatest with confirmed FDC, and
      diminished for probable and possible FDC, and IDC categories. LV dimensions
      increased and LV function worsened in index patients along the spectrum from
      confirmed FDC, probable FDC, possible FDC and IDC, and a greater proportion of
      IDC patients underwent heart transplant. However, the age of onset, duration of
      disease, the time to death or heart transplant, and most other findings were
      similar among the 4 categories. CONCLUSION: Clinical characteristics of IDC and
      FDC are similar, precluding an FDC diagnosis from clinical features only.

PMID- 16911909
TI  - Validation of prognostic models among patients with advanced heart failure.
AB  - BACKGROUND: The ability to accurately predict heart failure outcomes is essential
      to guiding treatment decisions but several competing risk stratification models
      exist. METHODS AND RESULTS: We prospectively collected data on 280 patients with
      advanced heart failure recruited from 16 sites across the United States. Deaths
      and cardiac transplantations within the following 4 years were identified.
      Medline was searched to systematically identify widely cited heart failure
      severity classification models predicting long-term survival among patients with
      heart failure, and 4 were selected for validation. We used Kaplan-Meier survival
      curves, receiver-operating characteristic curves, and Cox proportional hazards
      modeling to identify the prognostic significance of each model's risk score and
      the individual contribution of the clinical components within each model. Average
      follow-up was 31.2 months; 148 deaths or transplantations occurred. Each model
      that we evaluated identified patients with significantly different prognoses.
      However, each was limited in overall predictive power, and many component patient
      characteristics did not have independent prognostic significance. Prognostic
      factors found to be most powerful within their models included: increasing age,
      ischemic cardiomyopathy, history of cardiomyopathy, ankle edema, decreased peak
      oxygen consumption, and absence of beta-blocker use. CONCLUSION: Although each of
      the models succeeded in risk-stratifying patients to some extent, all 4 models
      had shortcomings. There is a need for a contemporary model, derived from a
      patient population managed in accordance with current heart failure guidelines,
      applicable to all heart failure etiologies, relying on readily available clinical
      data.

PMID- 16911910
TI  - Association of functional and health status measures in heart failure.
AB  - BACKGROUND: A wide variety of instruments have been used to assess the functional
      capabilities and health status of patients with chronic heart failure (HF), but
      it is not known how well these tests are correlated with one another, nor which
      one has the best association with measured exercise capacity. METHODS AND
      RESULTS: Forty-one patients with HF were assessed with commonly used functional,
      health status, and quality of life measures, including maximal cardiopulmonary
      exercise testing, the Duke Activity Status Index (DASI), the Veterans Specific
      Activity Questionnaire (VSAQ), the Kansas City Cardiomyopathy Questionnaire
      (KCCQ), and 6-minute walk distance. Pretest clinical variables, including age,
      resting pulmonary function tests (forced expiratory volume in 1 s and forced
      vital capacity), and ejection fraction (EF) were also considered. The association
      between performance on these functional tools, clinical variables, and exercise
      test responses including peak VO2 and the VO2 at the ventilatory threshold, was
      determined. Peak oxygen uptake (VO2) was significantly related to VO2 at the
      ventilatory threshold (r = 0.76, P < .001) and estimated METs from treadmill
      speed and grade (r = 0.72, P < .001), but had only a modest association with 6
      minute walk performance (r = 0.49, P < .01). The functional questionnaires had
      modest associations with peak VO2 (r = 0.37, P < .05 and r = 0.26, NS for the
      VSAQ and DASI, respectively). Of the components of the KCCQ, peak VO2 was
      significantly related only to quality of life score (r = 0.46, P < .05). Six
      minute walk performance was significantly related to KCCQ physical limitation (r
      = 0.53, P < .01) and clinical summary (r = 0.44, P < .05) scores. Among pretest
      variables, only age and EF were significantly related to peak VO2 (r = -0.58, and
      0.46, respectively, P < .01). Multivariately, age and KCCQ quality of life score
      were the only significant predictors of peak VO2, accounting for 72% of the
      variance in peak VO2. CONCLUSION: Commonly used functional measures, symptom
      tools, and quality of life assessments for patients with HF are poorly correlated
      with one another and are only modestly associated with exercise test responses.
      These findings suggest that exercise test responses, non-exercise test estimates
      of physical function, and quality of life indices reflect different facets of
      health status in HF and one should not be considered a surrogate for another.

PMID- 16911911
TI  - Clopidogrel is associated with a lesser increase in NT-proBNP when compared to
      aspirin in patients with ischemic heart failure.
AB  - BACKGROUND: Aspirin has been associated with adverse heart failure outcomes,
      probably because of a blunting interaction with angiotensin-converting enzyme
      (ACE) inhibitors. Therefore, we hypothesized that clopidogrel when compared with
      aspirin would be associated with a slower progression of heart failure as
      determined by levels of amino-terminal pro-brain natriuretic peptide (NT-proBNP).
      METHODS AND RESULTS: In an open-label, randomized, 2-treatment, 2-period
      crossover study, 18 patients with ischemic heart failure (14 post-myocardial
      infarction, left ventricular ejection fraction 0.32 +/- 0.08), median age 73, New
      York Heart Association class II (11 patients) or III (7 patients), all taking ACE
      inhibitors were included. Patients were randomized to 8 weeks of aspirin 100
      mg/day followed by 8 weeks of clopidogrel 75 mg/day, or the reversed sequence.
      Blood levels of NT-proBNP were measured using sandwich immunoassay. Patients on
      aspirin experienced an 8-times greater increase in log-transformed values of NT
      proBNP compared with patients on clopidogrel (average change 4.757% versus
      0.597%; P = .0395 for intervention, P = .4453 for period, P = .4046 for
      sequence). We observed no change in functional class, 6-minute walking test,
      creatinine levels, or electrolytes. CONCLUSION: Aspirin is associated with a
      greater increase in natriuretic peptides (log-transformed NT-proBNP levels),
      implying that aspirin therapy is associated with a more progressive course of
      heart failure.

PMID- 16911912
TI  - Neither race nor gender influences the usefulness of amino-terminal pro-brain
      natriuretic peptide testing in dyspneic subjects: a ProBNP Investigation of
      Dyspnea in the Emergency Department (PRIDE) substudy.
AB  - BACKGROUND: Amino-terminal pro-brain natriuretic peptide (NT-proBNP) is useful
      for the diagnosis and exclusion of congestive heart failure (HF). Little is known
      about the effect of race on NT-proBNP concentrations. Also, NT-proBNP levels may
      be higher in apparently well women, but the effect of gender on NT-proBNP
      concentrations in dyspneic patients is not known. METHODS AND RESULTS: NT-proBNP
      (Elecsys proBNP, Roche, Indianapolis, IN) was measured in 599 dyspneic patients
      in a prospective study. Of these, 44 were African American; 295 were female. NT
      proBNP levels were examined according to race and gender in patients with and
      without acute HF using analysis of covariance. Receiver operating characteristic
      (ROC) curves assessed NT-proBNP by race and gender. Cutpoints for diagnosis (450,
      900, and 1800 pg/mL for ages < 50, 50 to 75, and > 75 years) and exclusion (300
      pg/mL) were examined in African-American and female subjects. There was no
      difference in the rates of acute HF between African-American and non-African
      American (30% versus 35%, P = .44) or male and female (35% versus 35%, P = .86)
      subjects. In subjects with HF, there was no difference in median NT-proBNP
      concentrations between African American and non-African American (6196 versus
      3597 pg/mL, P = .37). In subjects without HF, unadjusted NT-proBNP levels were
      lower in African-American subjects than in non-African-American subjects (68
      versus 148 pg/mL, P < .03); however, when adjusted for factors known to influence
      NT-proBNP concentrations (age, prior HF, creatinine clearance, atrial
      fibrillation, and body mass index), race no longer significantly affected NT
      proBNP concentrations. There was no statistical difference in median NT-proBNP
      concentrations between male and female subjects with (4686 versus 3622 pg/mL, P =
      .53) or without HF (116 pg/mL versus 150 pg/mL, P = .62). Among African
      Americans, NT-proBNP had an area under the ROC for acute HF of 0.96 (P < .0001),
      and at optimal cutpoints, had a sensitivity of 100% and a specificity of 90%.
      Among females, NT-proBNP had an area under the ROC for acute HF of 0.95 (P <
      .0001), and had a sensitivity of 89% and a specificity of 88%; 300 pg/mL had
      negative predictive value of 100% in African Americans and females. CONCLUSION:
      NT-proBNP is useful for the diagnosis and exclusion of acute HF in dyspneic
      subjects, irrespective of race or gender.

PMID- 16911913
TI  - Arterial wave reflections are associated with left ventricular diastolic
      dysfunction in Adamantiades-Behcet's disease.
AB  - BACKGROUND: Adamantiades-Behcet's disease (ABD) is characterized by systemic
      vasculitis. We investigated whether aortic distensibility and arterial wave
      reflections are linked to left ventricular (LV) diastolic dysfunction in ABD.
      METHODS AND RESULTS: Eighty-two patients and 40 controls with similar
      atherosclerotic risk factors were examined by applanation tonometry of the radial
      artery (SphygmoCor) and echocardiography. Augmentation index (AI%) and arrival
      time (Deltat, ms) of reflected arterial waves as well as aortic distensibility
      (AoD) assessed by echocardiography were estimated. Doppler diastolic
      abnormalities were defined as proposed by the European Study Group on Diastolic
      Heart Failure by measurement of E/A ratio, isovolumic relaxation time,
      deceleration time, and flow propagation velocity. Patients had impaired central
      augmentation index (CAI), Deltat, and AoD compared with controls (P > .05). After
      adjusting for age, atherosclerotic risk factors, left ventricular mass, and
      medication the odds-ratio of AoD and CAI for left ventricular diastolic
      dysfunction was 0.664 (95%CI 0.449-0.982), P = .04, and 1.073 (95% CI 1.014
      1.140), P = .001, respectively. The addition of CAI to the multivariable model
      including AoD significantly increased the power of the model for prediction of
      left ventricular diastolic dysfunction (-2 Log likelihood change = 18.8, P for
      change > .01). CONCLUSION: Augmentation index has a complementary value to aortic
      distensibility in the assessment of left ventricular diastolic dysfunction in
      ABD.

PMID- 16911914
TI  - The impact of coenzyme Q10 on systolic function in patients with chronic heart
      failure.
AB  - BACKGROUND: Coenzyme Q10 (CoQ10) is an endogenous cofactor in the mitochondrial
      energy production. CoQ10 has been touted to improve heart failure, but its effect
      on systolic function is controversial. Several small, randomized controlled
      trials evaluating CoQ10 showed variable results and were largely underpowered. We
      conducted a meta-analysis of these trials to evaluate the impact of CoQ10 therapy
      on ejection fraction and cardiac output. METHODS AND RESULTS: A systematic
      literature search was conducted to identify randomized, controlled trials of
      CoQ10 in heart failure between 1966 and June 2005. Subgroup analysis was
      conducted to assess clinical heterogeneity between trials. Of the 11 trials
      identified, 10 evaluated ejection fraction (n = 277) and 2 evaluated cardiac
      output (n = 42). Doses ranged from 60 to 200 mg/day with treatment periods
      ranging from 1 to 6 months. There was a 3.7% net improvement in ejection fraction
      (95% CI 1.59-5.77; P < .00001 for statistical heterogeneity). A more profound
      effect among patients not receiving angiotensin-converting enzyme inhibitors was
      observed (6.74% [95% CI 2.63-10.86]). Cardiac output increased an average of 0.28
      L/minute (95% CI 0.03-0.53; P = .96 for statistical heterogeneity). CONCLUSION:
      CoQ10 enhances systolic function in chronic heart failure, but its effectiveness
      may be reduced with concomitant use of current standard therapies.

PMID- 16911915
TI  - The effect of statins in heart failure: beyond its cholesterol-lowering effect.
AB  - BACKGROUND: Statins known as 3-hydroxyl-3-methyl-glutaryl-coenzyme A (HMG-CoA)
      are designed to lower plasma cholesterol levels. They are used to treat
      hypercholesterolemia, ischemic heart disease patients, heart transplant
      recipients, in prevention of Alzheimer's dementia, multiple sclerosis, and have
      also been shown to reduce cancer risk. METHODS AND RESULTS: The idea of statin
      treatment in chronic heart failure is not well established. It has been shown to
      be beneficial in patients with ischemic heart disease with heart failure.
      Emerging trends show their usefulness in patients with nonischemic heart failure.
      Statins exhibit pleiotropic effects in stabilizing the atherosclerotic plaques,
      improvement of endothelial function, inhibition of cell migration and
      proliferation, and reduction of inflammation and oxidative stress. They also
      improve autonomic function with an increased parasympathetic drive, downregulate
      the angiotensin II type I receptors, and induce angiogenesis. CONCLUSION: This
      article is a review on the current knowledge on statin use in heart failure.

PMID- 16911916
TI  - p38 MAP kinase activity is correlated with angiotensin II type 1 receptor blocker
      induced left ventricular reverse remodeling in spontaneously hypertensive heart
      failure rats.
AB  - BACKGROUND: Angiotensin II type 1 receptor blocker L-158,809 (ARB) induces
      reverse left ventricular (LV) remodeling in spontaneously hypertensive heart
      failure (SHHF) rats. However, the signaling mechanism that mediates ARB-induced
      reverse LV remodeling remains unclear. The present study was to determine if
      changes in mitogen-activated protein kinase (MAPK, including ERK, JNK, and p38)
      signaling correlate with ARB-elicited reversal of cardiac hypertrophy in SHHF
      rats. METHODS AND RESULTS: In 1 set of experiments, 5-month-old lean female SHHF
      rats were treated with L-158,809 (ARB) or the vasodilator hydralazine (HYD) for 1
      month, respectively. In a second set of experiments, 5-month-old SHHF rats were
      treated with ARB for 6 months or 1 month and then with HYD for 5 months. Either
      ARB or HYD normalized left ventricular end systolic pressure in SHHF rats
      relative to normotensive control Wistar Furth (WF) rats at both 6 and 11 months
      of age, but only ARB reduced heart-to-body weight ratio in SHHF rats to control
      level. Western blot analysis showed that cardiac p38 MAPK activity was markedly
      increased in 6-month-old SHHF rats, but dramatically reduced in 11-month-old SHHF
      rats compared with WF rats, as indicated by the levels of phosphorylated form of
      p38. The alterations in p38 activity were completely reversed by ARB treatment
      but not by HYD treatment. CONCLUSION: ARB restored normal cardiac p38 activity,
      which coincided with ARB-induced reverse LV remodeling in SHHF rats, suggesting a
      strong correlation between p38 signaling and cardiac remodeling.

PMID- 16911917
TI  - Response to the February 2006 Journal of Cardiac Failure Editor's comment.

PMID- 16911918
TI  - Effects of specific endothelin-1 receptor antagonists on proliferation and
      fibronectin production of glomerular mesangial cells stimulated with Angiotensin
      II.
AB  - Angiotensin II (Ang-II) is a potent vasoactive hormone, which plays an important
      role in the pathogenesis of glomerulosclerosis. Ang-II activates many cytokine
      systems in the kidney. Recent studies indicate that Ang-II is closely related to
      the activation of the endothelin-1 (ET-1) system. The present study was designed
      to measure the [H3]-thymidine uptake and fibronectin production of cultured rat
      mesangial cells stimulated with Ang-II, and to evaluate the effects of specific
      ET-1 receptor antagonists, BQ123 (type A receptor antagonist) and IRL1038 (type B
      receptor antagonist) on the cells. ET-1 was measured by radioimmunoassay and
      fibronectin by Western blot analysis. The results were as follows: (1) Ang-II
      enhanced ET-1 production, [H3]-thymidine uptake, number of cells, and fibronectin
      production of mesangial cells; (2) all the baseline [H3]-thymidine uptake, number
      of cells, and fibronectin production of mesangial cells can be partly suppressed
      by BQ123, but not by IRL1038; (3) the increment of Ang-II-enhanced number of
      cells can be partly suppressed by BQ123, but not by IRL1038; and (4) the
      increment of Ang-II-enhanced fibronectin production can be partly suppressed by
      both BQ123 and IRL1038. Our results indicate that Ang-II is an active stimulant
      for the proliferation and fibronectin production of mesangial cells, and the
      effect is partly suppressed mainly by ET-1 type A receptor antagonists.

PMID- 16911919
TI  - Cut-off values of blessed dementia rating scale and its clinical application in
      elderly Taiwanese.
AB  - Although the Blessed Dementia Rating Scale (BDRS), a clinical screening
      instrument, has been applied extensively, no suitable cut-off values and clinical
      application have been proposed, particularly in mild cognitive impairment (MCI),
      the precursor of dementia. The BDRS, Mini Mental State Examination (MMSE), and
      Clinical Dementia Rating Scale (CDR) were administrated in people aged 65 years
      and above, who were enrolled from southern Taiwan with multistep stratified
      random sampling and followed-up for 2 years. All subjects (total number = 3,027),
      with new onset of MCI (defined as CDR = 0.5) in the first year and dementia
      (defined as CDR > or = 1) in the second and third years were subjected to
      statistical analysis. In distinguishing normal from MCI, except in the literate
      group aged 65-74 years, MMSE was superior to BDRS, with cut-off values of 1 in
      both literate groups aged 65-74 years and > or = 75 years, and 1.5 and 2 in less
      educated groups aged 65-74 and > or = 75 years, respectively. In distinguishing
      MCI from dementia, BDRS had cut-off values of 2.5 in both literate groups aged 65
      74 and > or = 75 years, and 2.5 and 3 in less educated groups aged 65-74 and > or
      = 75 years, respectively. These values were better than those for MMSE in all
      groups. BDRS might be considered as a better tool than MMSE to screen for MCI and
      dementia in the increasing proportion of literate elderly aged 65-74 years in the
      aging population.

PMID- 16911920
TI  - Effects of antibiotics and corticosteroid eyedrops on cellular proliferation in
      cultured human corneal keratocytes.
AB  - The purpose of this study is to investigate the effects of antibiotics and
      glucocorticoid eyedrops, including gentamicin, sulfisomezole, fluorometholone,
      dexamethasone, and betamethasone, on cellular proliferation in cultured human
      corneal keratocytes. Human corneal keratocytes were cultured in RPMI-1640
      containing 10% fetal bovine serum. Drugs were prepared from original
      concentrations to 1/10, 1/100, and 1/1,000 dilutions. After exposure to drugs for
      100 minutes, cellular proliferation was estimated by [3H]-thymidine uptake. It
      was found that cellular proliferation in corneal keratocytes was not affected by
      any of the three dilutions of gentamicin but was inhibited by 1/10 and 1/100
      dilutions of sulfisomezole to 82% and 90% of control. [3H]-thymidine uptake
      values were inhibited to 75% by 1/10 dilution of fluorometholone and by 1/10and
      1/100 dilutions of betamethasone to 84% and 86% of control. Meanwhile, cellular
      proliferation was significantly inhibited by 1/10, 1/100, and 1/1,000 dilutions
      of dexamethasone to 82%,86%, and 90%, respectively, in comparison with control
      values. It was demonstrated that commercial eyedrops of glucocorticoids inhibit
      cellular proliferation in corneal keratocytes, which may modulate the wound
      healing of corneal stroma.

PMID- 16911921
TI  - Correlates of attitudes toward homosexuality and intention to care for homosexual
      people among psychiatric nurses in southern Taiwan.
AB  - This study examined the association between attitudes toward homosexual
      individuals and intention to provide care and demographic and occupational
      factors, sexual orientation, knowledge about homosexuality, and experiences of
      contact with homosexual people among psychiatric nurses in southern Taiwan. In
      total, 133 psychiatric nurses from a medical center, three regional teaching
      hospitals, and one psychiatric hospital in southern Taiwan were recruited into
      this study. Their attitudes toward homosexual people as recorded on the Attitudes
      Toward Homosexuality Questionnaire, intention to provide care to homosexual
      individuals, and related factors were examined. The results revealed that
      psychiatric nurses who had a bachelor's or master's degree, higher level of
      knowledge about homosexuality, and friends or relatives with a homosexual
      orientation had a more positive attitude toward homosexuality. These psychiatric
      nurses, with more positive attitudes, and who worked in the medical center or
      regional teaching hospitals had a higher intention to care for homosexual people.
      The factors related to attitudes toward homosexuality and intention to care for
      homosexual people identified in this study should be taken into consideration
      when intervening in psychiatric nurses' attitudes toward homosexuality and
      intention to care for homosexual people.

PMID- 16911922
TI  - Ruptured sinus of valsalva and complete atrioventricular block complicating
      fulminant course of infective endocarditis: a case report and literature review.
AB  - Patients with infective endocarditis usually developed persistent fever and heart
      failure, especially when the valve structures are invaded and destroyed.
      Persistent bacteremia often leads to severe sepsis or overwhelming septic shock.
      Septic emboli from the vegetation will possibly result in systemic
      thromboembolism with multiple organ infarction. Patients with infective
      endocarditis have been reported to present with either ruptured sinus of Valsalva
      or complete atrioventricular block. However, both of these serious complications
      occurring in a single patient is rare. In this case report, we present a 54-year
      old man with a previous history of alcoholic cirrhosis and chronic renal failure
      who suffered from a fulminant course of infective endocarditis. Simultaneously,
      ruptured sinus of Valsalva and complete atrioventricular block further
      complicated the preexisting septic shock and multiple organ failure.

PMID- 16911923
TI  - Status epilepticus as an initial manifestation of neurosyphilis: a case report.
AB  - Seizures and focal neurologic deficits may be the complications of neurosyphilis,
      but status epilepticus as a presenting picture of neurosyphilis is rare. We
      describe a 41-year-old man with an acute onset of expressive dysphasia, followed
      by persistent seizure state and severe complications of systemic medical
      problems. An extensive laboratory evaluation confirmed the diagnosis of
      neurosyphilis and diabetes mellitus. Brain magnetic resonance imaging showed
      edematous change in the left cingulate gyrus, left temporal lobe, and peri
      Rolandic area, which suggested an inflammatory process. Due to varied clinical
      manifestations of neurosyphilis, we underscore the importance of considering
      neurosyphilis among the possible causes of status epilepticus and any central
      nervous system diseases.

PMID- 16911924
TI  - Successful thrombolytic therapy for bilateral renal infarction: a case report.
AB  - Acute renal infarction is a rarely reported disease in the medical literature.
      Angiography, renal scintigraphy, intravenous pyelography, sonography, and
      enhanced computed tomography may be useful in diagnosing acute renal infarction
      antemortem. Therapeutic guidelines for the treatment of renal infarction have not
      been established. We report a case of bilateral renal infarction in an elderly
      woman with atrial fibrillation, which was successfully treated by thrombolytic
      therapy.

PMID- 16911925
TI  - Mycobacterium abscessus cervical lymphadenitis: an immunocompetent child.
AB  - Nontuberculous mycobacterium (NTM) is one of the well-known causes of
      cervicofacial lymphadenopathy in children under 5 years of age. Children often
      present with a painless cervical mass that fails to respond to conventional
      antibiotics. They are often referred under the suspicion of a neoplasm or
      bacterial adenitis rather than NTM cervical lymphadenitis. The lack of systemic
      symptoms, modest or negative purified protein derivative test and absence of
      exposure to active tuberculosis are characteristics of NTM lymphadenitis. The
      diagnosis usually requires the isolation of pathogen or pathologic proof.
      Complete excision is the choice of treatment by the majority of authors in the
      literature. This not only enables rapid diagnosis but ensures the lowest
      recurrence rate. Medical management is sometimes successful when complete
      resection is impossible or refused. To our knowledge, the incidence of NTM
      cervical lymphadenitis in children is increasing throughout the world. However,
      such reports of children in Taiwan is lacking. Clinicians should suspect a
      possible nontuberculous mycobacterial infection when a cervical lump is found in
      a child.

PMID- 16911926
TI  - Pain relief in upper abdominal malignancy.

PMID- 16911927
TI  - Hyperplastic cholecystoses: efforts should be made to recognize and treat them.

PMID- 16911928
TI  - Genetic factors for individual administration of immunosuppressants in organ
      transplantation.
AB  - BACKGROUND: The immunosuppressive drugs used worldwide have a narrow therapeutic
      index, which results in a need to individualize the dose regimen for different
      recipients. The oxidative enzymes cytochrome P450 (CYP)3A and the drug efflux
      pump P-glycoprotein (P-gp) are two potential factors in the processes of
      metabolism. Pharmacogenetic study of immunosuppressive drugs has focused on these
      two enzymes. This review was undertaken to assess the role of single nuclear
      polymorphisms (SNPs) of these two enzymes in the individual administration of
      immunosuppressive drugs. DATA SOURCES: An English-language literature search was
      made using MEDLINE for articles on CYP3A and P-gp in organ transplantation.
      RESULTS: The SNPs of CYP3A and P-gp are closely correlated to the large
      variations of cyclosporine and tacrolimus dosage between different patients,
      although conflicting results were obtained by some authors. CONCLUSIONS: More
      studies should be conducted to elucidate further the pharmacogenetics of
      immunosuppressive drugs in organ transplantation, a deep understanding of which
      would provide an important step toward drug regimen individualization in the
      posttransplant therapy.

PMID- 16911929
TI  - Problems in adult living donor liver transplantation using the right hepatic
      lobe.
AB  - BACKGROUND: Adult living donor liver transplantation (LDLT) is now widely applied
      to patients, children or adults, and the graft extends from the left hepatic lobe
      to the right hepatic lobe. Harvesting the right hepatic lobe would mean putting
      the donor at high risk. The congestion of a graft may cause small-for-size
      syndrome. The safety of the donor and its evaluation, which are related to the
      outcome for the recipient, play an important role in LDLT. How to decrease the
      congestion of the graft is another challenge to transplant experts. DATA SOURCES:
      A literature search from MEDLINE about adult LDLT in recent years was made to
      analyze the safety of the living donor and the innovation of surgical techniques
      for preventing small-for-size syndrome. RESULTS: The top priority for adult LDLT
      is donor safety. Preoperative donor evaluation consists of three stages: phase 1
      for general evaluation, phase 2 for laboratory tests, and phase 3 for
      radiological evaluation of graft volume and vessel anatomy. The potential
      pathogenic mechanisms of small-for-size syndrome seem to be related to persistent
      portal hypertension and portal overperfusion. Improved surgical techniques for
      decreasing portal hypertension and preventing congestion of a graft may reduce
      the incidence of small-for-size syndrome. The improved techniques include
      reconstruction of the tributaries of the middle hepatic vein, end-to-side
      portocaval shunting, ligation of the splenic artery, dual-graft transplantation,
      and modified reconstruction of hepatic veins. CONCLUSION: With the careful
      preoperative assessment and the safety of the living donor, as well as improved
      surgical techniques, adult LDLT using the right lobe is safe.

PMID- 16911930
TI  - Current therapy with nucleoside/nucleotide analogs for patients with chronic
      hepatitis B.
AB  - BACKGROUND: Currently, more and more nucleos(t)ide analogs are appearing as
      therapeutic options in the treatment of chronic hepatitis B (CHB). Their efficacy
      and safety profile in hepatitis B virus (HBV) infection have already been studied
      in detail worldwide. This review summarizes the efficacy of lamivudine, adefovir,
      entecavir and newer antiviral agents such as emtricitabine, telbivudine and
      clevudine in the treatment of hepatitis B in different clinical situations. DATA
      SOURCES: An English-language literature search using OVID and MEDLINE was
      performed and a total of 40 articles on the treatment of chronic hepatitis with
      nucleos(t)ide analogues were selected. RESULTS: Nucleos(t)ide analogs such as
      lamivudine, adefovir and entecavir are well tolerated and induce a decrease in
      serum HBV-DNA levels associated with normalization of serum alanine
      aminotransferase (ALT) levels. But their sustained response with HBeAg to anti
      HBe seroconversion is rarely obtained and HBsAg loss is exceptional. The response
      is maintained during therapy which needs to be continued indefinitely in the
      majority of patients since withdrawal of treatment is generally followed by a
      rapid reactivation of hepatitis B. However, drug resistant mutations can be
      induced in long-term treatment. Other newer antiviral agents such as
      emtricitabine, telbivudine and clevudine in the treatment of hepatitis B are
      still under phase II or III clinical trials. CONCLUSIONS: Nucleos(t)ide analogs
      play an important role in the therapy of hepatitis B now and in the future.
      Lamivudine is limited by the frequent emergence of drug-resistant (HBV) mutants
      (YMDD). Adefovir and entecavir appear to be effective against both YMDD mutation
      and wild type. Therapeutic options against hepatitis B virus remain a major
      clinical challenge.

PMID- 16911931
TI  - Intramuscular hepatitis B immune globulin combined with lamivudine in prevention
      of hepatitis B recurrence after liver transplantation.
AB  - BACKGROUND: Combined hepatitis B immune globulin (HBIg) and lamivudine in
      prophylaxis of the recurrence of hepatitis B after liver transplantation has
      significantly improved the survival of HBsAg positive patients. This study was
      undertaken to evaluate the outcomes of liver transplantation for patients with
      hepatitis B virus (HBV). METHODS: A retrospective chart analysis and a review of
      the organ transplant database identified 51 patients (43 men and 8 women)
      transplanted for benign HBV-related cirrhotic diseases between June 2002 and
      December 2004 who had survived more than 3 months. HBIg was administered
      intravenously during the first week and intramuscularly thereafter. RESULTS: At a
      median follow-up of 14.1 months, the overall recurrence rate in the 51 patients
      was 3.9% (2/51). The overall patient survival was 88.3%, and 82.4% after 1 and 2
      years, respectively. A daily oral dose of 100 mg lamivudine for 2 weeks before
      transplantation for 10 patients enabled 57.1% (4/7) and 62.5% (5/8) of HBV-DNA
      and HBeAg positive patients respectively to convert to be negative. Intramuscular
      HBIg was well tolerated in all patients. CONCLUSION: Lamivudine combined with
      intramuscular HBIg can effectively prevent allograft from the recurrence of HBV
      after liver transplantation.

PMID- 16911932
TI  - The scoring system for patients with severe sepsis after orthotopic liver
      transplantation.
AB  - BACKGROUND: Because of the complicated pathological features after liver
      transplantation, severe sepsis is difficult to treat and often leads to death.
      This study was undertaken to analyze the role of orthotopic liver transplantation
      (OLT) in patients with severe sepsis and to evaluate the effect of the scoring
      system. METHODS: Fifty-six patients conformed to the inclusion criteria. They
      were divided into two groups: non-OLT group (group A) and OLT group (group B).
      Besides the general data of the patients, the surveillance of blood lactate, the
      number of failed organs, acute physiology and chronic health evaluation II
      (APACHE II ) and multiple organ dysfunction score (MODS) were evaluated at the
      1st, 3rd and 7th day after OLT. RESULTS: The mortality during hospitalization was
      30% in the non-OLT group and 57.6% in the other group. The level of blood lactate
      at the 1st day of OLT increased more significantly in the OLT group than in the
      non-OLT group (P<0.01). It was decreased but higher than that in the non-OLT
      group in the seven days after OLT. The number of failed organs in the OLT group
      was greater than that in the non-OLT group (P<0.01). The continuous score of
      APACHE II was not significantly different in the two groups. But the continuous
      MODS in the OLT group was higher than that in the non-OLT group (P<0.01), which
      was consistent with the number of failed organs. CONCLUSIONS: The persistently
      higher level of blood lactate during 7 days may be a dependent risk factor.
      Immunosuppression may be another risk factor for OLT patients. The mortality of
      OLT in patients with severe sepsis in 28 days is almost double that in non-OLT
      patients. The MODS score is better than the APACHE II score in the assessment of
      organ failure in OLT patients with severe sepsis. The standard scoring system
      could be improved or a new scoring system that includes the blood lactate score
      should be established for liver transplantation.

PMID- 16911933
TI  - Is there any difference in anesthetic management of different post-OLT stage
      patients undergoing nontransplant organ surgery?
AB  - BACKGROUND: Little information is available about anesthesia management of
      nontransplant organ surgery of recipients after adult liver transplantation. The
      aim of this study was to discuss the anesthesia management of recipients for
      different stages after liver transplantation. METHODS: The medical records of 16
      patients were reviewed after OLT scheduled for elective nontransplant organ
      surgery at our institution from September 2002 to October 2005. The patients were
      divided into perioperative stage (group A) and mid-term and long-term stage
      (group B) groups according to post-OLT time. The data of 16 patients
      preoperation, intraoperation and postoperation were analyzed. RESULTS: The
      measurements of alanine transaminase (ALT), total bilirubin (TB), prothrombin
      time (PT), and lung infection were significantly higher in group A than in group
      B (P<0.05). The incidence of hyperglycaemia was significantly higher in group B
      than in group A (P<0.05). During operation the incidence of hypotension was
      significantly higher in group A than in group B (P<0.05). After operation, the
      number of patients in ICU was significantly larger and the extubation time was
      longer in group A than in group B. General anesthesia was induced in 14 patients,
      and regional anesthesia in 2 patients. CONCLUSIONS: Regional or general
      anesthesia can be safely delivered to adult OLT recipients except for
      contraindications. Special considerations include protection of the function of
      important organs, correction of hemodynamic instability in perioperative stage
      patients after OLT, and measurement of the side-effects of immunosuppression in
      mid-term and long-term stage patients.

PMID- 16911934
TI  - Combination of pegylated interferon and lamivudine for patients with chronic
      hepatitis B who have failed treatment.
AB  - BACKGROUND: Treatment of chronic hepatitis B (CHB) alone with interferon or
      lamivudine alone or in combination is effective in only a small proportion of
      patients. Treatment of patients in whom antiviral therapy fails is challenging.
      This study was made to determine the efficacy of combined pegylated interferon
      alpha (peg-IFN) and lamivudine in patients with CHB who had failed to respond to
      antiviral treatment. METHODS: Twenty patients with CHB proven by liver biopsy,
      with ALT levels >1.5 X ULN, HBV DNA levels>141,500 copies/ml, and previous
      treatment failure with an adequate regimen were treated with a combination of peg
      IFN 1.5 microg/kg and lamivudine 100 mg/day for 52 weeks and followed up for a
      further 24 weeks. Biochemical response was defined as normalization of ALT and
      DNA response as HBV DNA<141,500 copies/ml. Secondary efficacy measures included
      HBsAg loss, HBeAg loss and appearance of anti-HBe (in cases of HBeAg-positive
      patients). RESULTS: Twenty patients were treated, of whom 16 were HBeAg positive.
      At 52 weeks, normal ALT was seen in 10 (50%) (8 of 16 HBeAg+ and 2 of 4 HBeAg-),
      HBV DNA response in 5 (25%) (5 of 16 in HBeAg+ and none in HBeAg-), and HBeAg
      loss with appearance of anti-HBe in 5 (31.3%) of the 16 HBeAg positive patients.
      At 76 weeks, 8 (80%) of the 10 patients with normal ALT at 52 weeks relapsed,
      with normal ALT only in 2 (10%) (1 of 16 HBeAg+ and 1 of 4 HBeAg-), and all 5
      patients who had a DNA response at 52 weeks relapsed at 76 weeks and had no DNA
      response. HBeAg loss with appearance of anti-HBe was seen in 1 (6.3%) of 16 HBeAg
      positive patients. None of the patients lost HBsAg. CONCLUSIONS: The combination
      of peg-IFN and lamivudine for 52 weeks is not effective for treatment of CHB
      patients with a failed treatment. New treatment strategies need to be developed.

PMID- 16911935
TI  - Abnormal expression of HSP gp96 associated with HBV replication in human
      hepatocellular carcinoma.
AB  - BACKGROUND: Heat shock protein (HSP) gp96 is a member of the HSP90 family and
      presumably overexpresses as a result of stimulation by mutated or abnormal
      proteins. Its abnormal expression correlates with carcinogenesis, progression and
      prognosis of hepatocellular carcinoma (HCC). In this study, we investigated the
      pathological characteristics of liver gp96 expression and its relationship with
      hepatitis B virus (HBV) replication in HCC patients. METHODS: Tumor specimens
      were prospectively collected from 30 HCC patients undergoing liver resection.
      Total RNAs were extracted from HCC or their non-cancerous tissues. The
      distribution of gp96 expression in hepatocytes was investigated by streptavidin
      peroxidase (S-P) immunohistochemistry and tissue HBV-DNA was detected by the in
      situ molecular hybridization technique. The association of gp96 expression with
      HBV replication, and the histopathological characteristics of HCC were analyzed.
      RESULTS: The gp96 was strongly expressed in HCC (73.3%, 22 of 30) and weakly
      (46.7%, 14 of 30) in non-cancerous tissues. The gp96 expression in HCC tissues
      was correlated with degree of tumor differentiation and tumor size, but not with
      tumor number (P>0.05). Immunohistochemical analysis showed that 17 of 19 HCC
      patients with HBV-DNA-positive were strongly expressed for gp96, whereas only 5
      of 11 patients with HBV-DNA-negative were positive for gp96. A significant
      difference was found between the two groups (89.5% vs. 45.5%, P<0.05).
      CONCLUSIONS: The abnormal expressions of HSP gp96 in HCC tissues are associated
      with HBV replication. This finding indicates that HBV infection plays an
      important role in the development of HCC.

PMID- 16911936
TI  - Caudate lobectomy by the third porta hepatis anatomical method: a study of 16
      cases.
AB  - BACKGROUND: The treatment for primary tumor in the caudate lobe of the liver is
      difficult because of its unique anatomical location. This study was undertaken to
      improve operative techniques and results by a new anatomical method of caudate
      lobectomy. METHODS: Clinical data of 16 patients who had had caudate lobectomy
      for the liver from January 1996 to November 2004 were retrospectively analyzed.
      The third porta hepatis anatomical method was performed in all 16 patients.
      Operative time, intraoperative blood loss, postoperative complications were
      recorded. The 1-, 3-, and 5-year survival rates of 13 patients with caudate lobe
      carcinoma were followed up. Anatomical status, operative routes, operative
      procedures, liver blood supply were evaluated. RESULTS: The operation was
      successful in the 16 patients. The operative time was 255+/-70 minutes and blood
      loss 740+/-402 ml. None of the patients died from massive bleeding during the
      operation, nor did complications such as biliary fistula and liver failure
      occurred. In 13 patients with malignant tumor, 7 died from recurrence and
      metastasis of the tumor and the other 6 are still alive at the end of follow-up.
      One patient has survived for 6 years. The 1-, 3-, and 5-year survival rates in
      the 13 patients were 83.9%, 58.7% and 39.2%, respectively. CONCLUSION: Caudate
      lobectomy by the third porta hepatis anatomical method can improve operative
      effect and increase the resection probability for solitary tumor in the caudate
      lobe.

PMID- 16911937
TI  - Implantation of a drug delivery system during surgery for patients with primary
      hepatocarcinoma.
AB  - BACKGROUND: Postoperative regional chemotherapy is one of the most effective
      methods to decrease the recurrent rate and improve the prognosis of primary
      hepatocarcinoma (PHC). This study was undertaken to assess the optimal pathway to
      implant the drug delivery system (DDS) in the different ways of resecting PHC so
      as to offer a valuable reference to clinical implantation of the DDS. METHODS:
      One hundred and ninety cases were divided into two groups according to whether
      the tumors were resected completely (A) or not (B). Groups A and B were
      subdivided into three groups a, b and c according to the pathway selected for DDS
      implantation. The patients in subgroup a received DDS implantation through both
      the hepatic artery and portal vein (A+P-implanted group), the patients in
      subgroup b received DDS implantation through the portal vein (P-implanted group),
      and the patients in subgroup c received DDS implantation through the hepatic
      artery (A-implanted group). RESULTS: The 1- and 3-year recurrent rates of
      subgroup c in group A were higher than those of subgroup b, and there was no
      significant difference between subgroups a and b. Compared with subgroups a and
      c, the 1- and 3-year survival rates of subgroup b were similar to those of group
      a but higher than those of group c. The 1- and 3-year survival rates between
      subgroups a and b in group B were significantly different. The prognosis of
      subgroup c was lower than that of subgroup a and no significant difference was
      observed between subgroups b and c. CONCLUSIONS: The DDS should be implanted into
      the portal vein when PHC is resected completely. It may be better to implant it
      into both portal vein and hepatic artery if the tumor cannot be completely
      resected.

PMID- 16911938
TI  - Surgical treatment for hepatocellular carcinoma and secondary hypersplenism.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is a common disease with high
      mortality and serious effect on the life quality of patients. Operation is still
      the most effective treatment. Currently, in China, patients with HCC are often
      complicated by hepatitis B related liver cirrhosis and secondary hypersplenism.
      This study was undertaken to evaluate the effect and indications of synchronous
      hepatectomy and splenectomy for HCC patients with hypersplenism. METHODS: The
      clinical records and treating processes of 24 patients with HCC and hypersplenism
      during the period of January 1991 to July 2004 were analyzed retrospectively.
      RESULTS: Sixteen patients underwent hepatectomy and splenectomy, including
      extensive devascularizasion around the cardia (9 patients). Seven patients were
      treated with microwave ablation and splenectomy plus extensive esophagogastric
      devascularization. One patient underwent hepatectomy combined with microwave
      ablation and splenectomy plus extensive esophagogastric devascularization. There
      were no deaths during the operation. During the first week after operation, the
      symptoms of hypersplenism disappeared and the platelet (Plt) and white blood cell
      (WBC) counts were significantly elevated (Plt: 247 X 10(9)/L vs. 45.9 X 10(9)/L,
      WBC: 13.0 X 10(9)/L vs. 3.3 X 10(9)/L, P<0.01). CONCLUSIONS: Synchronous
      splenectomy can increase the safety of hepatectomy in selected patients with HCC
      and secondary hypersplenism by reducing bleeding complications. Splenectomy
      enhances patients' immunity against tumor in a long period as well.

PMID- 16911939
TI  - Ultrasonographic findings at the resected area after hepatectomy.
AB  - BACKGROUND: Since hepatectomy has been widely performed, different operative
      manner, operating areas, and material in the residual cavity may be found
      ultrasonographically near the resected area after the operation. In this study,
      we investigated the changes of focal ultrasonography at the resected area post
      hepatectomy and recognized the characteristic ultrasonographic images. METHODS:
      176 patients whose ultrasonographic findings were studied in the residual area
      during the early and later periods after hepatectomy were retrospectively
      analyzed in terms of operative manner, operative area, and material in the
      residual cavity. RESULTS: There were absence of partial hepatic lobe or hepatic
      segment, focal anechoic area with thin wall or mixed mass at the resected area,
      and conformation of irregular high-echoic conglomeration at the resected area,
      cystic non-anechoic area, and mixed mass with irregularly thickened wall at the
      resected area, inconsistent internal echoes, and color Doppler twinking artifacts
      around the material and the residual cavity after curettage and aspiration.
      CONCLUSIONS: Focal ultrasonographic findings at the resected area after
      hepatectomy vary with different operative procedures, operative area, resection
      size, absence or existence of material, and kinds of material in the residual
      cavity.

PMID- 16911940
TI  - Hepatic veno-occlusive disease induced by Gymura segetum: report of two cases.
AB  - BACKGROUND: Hepatic veno-occlusive disease (VOD) or sinusoidal obstruction
      syndrome is associated with a high mortality because of its severity. Gymura
      segetum, a Chinese herbal medicine, is always used to cure injury and bleeding in
      rural areas in China. This study was undertaken to better understand VOD and its
      relations to the effect of Gymura segetum. METHODS: Between 2000 and 2002, two
      patients were admitted to our department because of VOD. Before admission, both
      of them had been injured and taken oral decoction of patent drug Gymura segetum.
      We analyzed the clinical manifestations, diagnosis and therapy of the two
      patients. RESULTS: Pyrrolizidine in Panax notginseng was proved to induce VOD.
      The diagnosis of VOD depended on hepatic biopsy. CONCLUSION: Gymura segetum can
      induce VOD. More attention should be paid to its unsuscepted side effects.

PMID- 16911942
TI  - Gene expression changes after hypoxic preconditioning in rat hepatocytes.
AB  - BACKGROUND: Hypoxic preconditioning can protect hepatocytes against hypoxic
      injury, but its mechanism has not been elucidated. The aim of this study was to
      profile gene expression patterns involved in hypoxic preconditioning and probable
      mechanism at the level of gene expression. METHODS: Hepatocytes were divided into
      2 groups: control group and hypoxic preconditioning group. Biotin-labeled cRNA
      from the control group and the hypoxic preconditioning group was hybridized by
      oligonucleotide microarray. Genes that were significantly associated with hypoxic
      preconditioning were filtered, and validated at the level of transcript
      expression. RESULTS: Forty-three genes with significantly altered expression
      patterns were discovered and most of them had not been previously reported. Among
      these genes, genes encoding superoxide dismutase 2 (SOD2) and interleukin 10 (IL
      10) in the hypoxic preconditioning group were confirmed to be up-regulated with
      real-time quantitative PCR. CONCLUSIONS: Many cytokines are involved in hypoxic
      preconditioning and protect hepatocytes from hypoxia-reoxygenation injury, and
      the increase of oxygen free-radical scavengers and anti-inflammatory factors may
      play a key role in this phenomenon. Diverse signal pathways are probably
      involved.

PMID- 16911941
TI  - Overexpression of TIMP-1 mediated by recombinant adenovirus in hepatocellular
      carcinoma cells inhibits proliferation and invasion in vitro.
AB  - BACKGROUND: Matrix metalloproteinases (MMPs) and its natural tissue inhibitors of
      metalloproteinases (TIMPs) are involved in cancer progression. This study was
      undertaken to determine the effects of overexpression of TIMP-1 on human
      hepatocellular carcinoma (HCC) cell growth, proliferation, and invasion. METHODS:
      Employing the efficient AdEasy(TM) system, recombinant adenovirus AdTIMP-1
      containing full-length cDNA of TIMP-1 was generated by homologous recombination
      and amplified in 293 cells. Then, human HCC cell line (HepG2) underwent gene
      transfection to overexpress TIMP-1 (so-called HepG-T cells). The mRNA and protein
      expressions of TIMP-1 were detected with RT-PCR and Western blotting,
      respectively. The ultrastructure was observed with a transmission electron
      microscope and the proliferation of HepG-T cells was determined by MTT assay and
      growth curve. The potential of in vitro invasion was measured with Millicell
      Chamber. RESULTS: The resulting AdTIMP-1 and HepG-T cells were generated and the
      expression of TIMP-1 was detected in vitro. The cell proliferation curves and MTT
      assay showed HepG-T cells' growth, and proliferation were obviously inhibited.
      The invasion across Matrigel-coated filters was significantly decreased compared
      with controls. The suppression rate of HepG-2 cells with AdhTIMP-1 transfection
      was 50%, and AdhTIMP-1 transfection inhibited by more than 91.6% of the invasion
      into the Matrigel-coated filter (P<0.01). CONCLUSIONS: TIMP-1 overexpression
      results in the suppression of proliferative and invasive potential of HepG2 cells
      in vitro. This study demonstrates the potential role of TIMP-1 as a target for
      liver cancer gene therapy and has laid a foundation for further study on its
      anticancer function.

PMID- 16911943
TI  - Effects of cytotoxic T lymphocytes on hepatoma cell line SMMC-7721 induced by
      different subsets of dendritic cells in vitro.
AB  - BACKGROUND: Dendritic cells (DCs) loaded with complex antigen are always used to
      induce cytotoxic T lymphocytes (CTLs) which have a specific anti-tumor activity.
      However, CTLs can assault autologous cells induced by DCs loaded with autologous
      antigen. This study aimed to explore how to weaken the autoimmune reaction
      induced by DC vaccine by combining mature DC (mDC) activating immunity and
      immature DC (imDC) leading to immune tolerance to make hepatocellular carcinoma
      (HCC) vaccine in vitro. METHODS: DC progenitors derived from human peripheral
      blood were assigned to two groups. One was cultured to mDC and pulsed with frozen
      thawed antigen (FTA) of human HCC cell line SMMC-7721 cells (mDC group), and the
      other was cultured to imDC and pulsed with FTA of human liver cell line L-02
      cells (imDC group). The morphology of DCs was monitored and cells phenotypes
      including HLA-DR, CD80, CD1alpha, CD83 were assayed by flowcytometry (FCM). The
      concentrations of interleukin-12 (IL-12) in the supernatant were assayed by
      ELISA. Methyl thiazolyl tetrazolium (MTT) was used to evaluate T cell
      proliferation induced by mDC and imDC and the killing rate of CTL induced by mDC
      and imDC respectively/together on SMMC-7721 and L-02 cells. RESULTS: Compared
      with the imDC group, the mDC group was characterized by the following: increased
      secretion of IL-12 (P<0.05); higher expression of HLA-DR, CD1alpha, CD80, CD83;
      and stronger activity in stimulating proliferation of isogenic T cells (P<0.05).
      CTL induced by the mDC group had a significant killing response to SMMC-7721 as
      well as a higher killing rate for L-02 (P>0.05). CTL induced by mDC and imDC
      together had a higher killing response to SMMC-7721, but a lower killing rate for
      L-02 (P<0.01). CONCLUSIONS: CTL induced by mDC and imDC together has a higher
      antigen-specific killing response in vitro than that induced by mDC alone. This
      may be of greater clinical value.

PMID- 16911944
TI  - Protective effects of N-acetylcysteine on brain-dead rat liver.
AB  - BACKGROUND: Brain-dead donors have been the main sources in organ
      transplantation. But many studies show that brain-death affects the organ's
      function after transplantation. This study was undertaken to investigate liver
      injury after brain-death in rats and the protective effects of N-acetyleysteine
      (NAC) on liver injury. METHODS: A total of 30 Wistar rats were randomized into 3
      groups: normal control group (C), brain-dead group (B), and NAC pretreatment
      group (N). At 4 hours after the establishment of a brain-dead model, serum was
      collected to determine the levels of ALT, AST, TNF-alpha and hyaluronic acid
      (HA). Hepatic tissue was obtained for electron microscopic examination. RESULTS:
      At 4 hours, the levels of ALT, AST, TNF-alpha, and HA in group N were
      significantly higher than those in group C, but these parameters were
      significantly lower than those in group B. Electron microscopy showed activated
      Kupffer cells, denuded sinusoidal endothelial cells (SECs), and widened
      fenestration in group B, but eliminated activation of Kupffer cells and intact
      SECs in group N. CONCLUSION: Brain death can cause liver injury, and N
      acetyleysteine can protect the liver from the injury.

PMID- 16911945
TI  - Effect of L-arginine on calcium in hepatic mitochondrion in rats with obstructive
      jaundice.
AB  - BACKGROUND: There is much debate over the regulation of mitochondrial calcium
      overload and reducing the impairment of energy metabolism in hepatic cells. It
      has not been reported whether L-arginine (L-Arg) can affect hepatic mitochondrial
      calcium overload. This study was undertaken to investigate the protective effect
      of L-Arg on Ca2+ handling of hepatic mitochondrion in rats with obstructive
      jaundice and to clarify its possible mechanism. METHODS: Seventy-two male SD rats
      were randomly divided into 3 groups: sham operation+normal saline group (SO
      group), common bile duct ligation+normal saline group (BDL group), and common
      bile duct ligation+ L-Arg group (L-Arg group). The levels of malondialdehyde
      (MDA), superoxide dismutase (SOD) and Ca2+ in rat hepatic mitochondrion were
      examined at the 7th, 14th and 21st day after operation. RESULTS: The Ca2+ and MDA
      levels of hepatic mitochondrion increased significantly but their SOD content
      decreased markedly at each time point in the BDL group. Except at the 21st day,
      the Ca2+ and MDA, contents of hepatic mitochondrion were significantly lower, and
      SOD concentrations were higher in the L-Arg group than those in the BDL group at
      the 7th and 14th day (P<0.01). CONCLUSION: L-Arg has a protective effect on
      mitochondrion in the early and mid stages of obstructive jaundice.

PMID- 16911946
TI  - Neutrophil-mediated liver injury during hepatic ischemia-reperfusion in rats.
AB  - BACKGROUND: Neutrophil plays an important role in hepatic ischemia-reperfusion
      injury. We investigated neutrophil infiltration in liver tissue, Kupffer cells'
      role in neutrophil accumulation, and apoptosis and regeneration of hepatocytes in
      liver ischemia-reperfusion injury. METHODS: Vascular microclamps were placed
      across the pedicles of the median and left lateral lobes for 90 minutes after 30%
      hepatectomy with the resection of caudate, right lateral and quadrate lobes and
      papillary process. Gadolinium chloride (GdCl(3)) was used to destroy Kupffer
      cells. Neutrophil activity was inhibited with Urge-8, a monoclonal antibody
      against neutrophil produced in our laboratory. GdCl(3) (10 mg/kg) and Urge-8 (50
      mg/kg) were given intravenously in respective groups. Ischemia control, GdCl(3)
      and Urge-8 groups were compared. RESULTS: Following hepatic reperfusion, serum
      interleukin-8 (IL-8) levels and hepatic neutrophil counts peaked at 3 hours, and
      peak concentrations of alanine aminotransferase (ALT) occurred at 6 hours.
      Animals of the control group showed increases in neutrophil infiltration in liver
      tissue, liver enzyme levels, and apoptosis index of hepatocytes and decreases in
      overall survival rate and proliferating cell nuclear antigen (PCNA) expression of
      hepatocytes. The survival rates and PCNA proportion of hepatocytes were higher
      and the levels of hepatic neutrophil infiltration, liver enzymes, and hepatocyte
      apoptosis after reperfusion were lower in the GdCl(3) and Urge-8 groups than
      those in the ischemia control group. CONCLUSIONS: Blockades of Kupffer cells'
      activity and neutrophil infiltration by GdCl(3) and Urge-8 eliminate neutrophil
      mediated hepatic injury and enhance subsequent hepatic regeneration during liver
      ischemia-reperfusion.

PMID- 16911947
TI  - Role of intestinal barrier in pathogenesis of pigment gallstone in a guinea pig
      model.
AB  - BACKGROUND: The function of the intestinal barrier has drawn more and more
      attention from researchers in recent years for its important role in many
      diseases such as burns, wounds, and pancreatitis. In our experimental studies on
      pigment gallstone, we found potential relationships between the function of the
      intestinal barrier and pigment gallstone formation. This study was undertaken to
      investigate the possible action and mechanism of the function of the intestinal
      barrier in the pathogenesis of pigment gallstone. METHODS: Eighty guinea pigs
      were divided into a normal group (CON), a pigment gallstone group (PS) and an
      intestinal mucosa protection group (GLN). Normal forage, pigment gallstone
      forming forage and pigment gallstone-forming forage with supplemental intestinal
      mucosa protector (glutamine) were given to each group. In the gallstone-forming
      rate, morphology of intestinal mucosa, intestinal permeability, serum endotoxin
      and biliary beta-glucuronidase were assessed after 8 weeks. RESULTS: The rate of
      gallstone-formation was 73.9% in the PS group. Damage of intestinal mucosa,
      endotoxemia (from 77+/-43 X 10(-6) EU/L to 1,367+/-525 X 10(-6) EU/L, P<0.01) and
      increased activity of biliary beta-glucuronidase (endogenous beta-glucuronidase
      from 122.1+/-39.5 to 209.8+/-47.5 Fishman Unit, P<0.01, and exogenous beta
      glucuronidase from 573.5+/-476.9 to 2,206.6+/-983.9 Fishman Unit, P<0.01) were
      observed in the PS group compared with the CON group. The rate gallstone
      formation decreased significantly to 44.4% and the other indices except beta
      glucuronidase were lower in the GLN group than in the PS group. CONCLUSIONS: The
      function of the intestinal barrier is correlated with pigment gallstone
      formation. Dysfunction of the intestinal barrier function may promote pigment
      gallstone formation through bacterial translocation, endotoxemia, and biliary
      beta-glucuronidase.

PMID- 16911948
TI  - The methylation status of the TMS1/ASC gene in cholangiocarcinoma and its
      clinical significance.
AB  - BACKGROUND: TMS1/ASC is a bipartite protein comprising two protein-protein
      interactive domains: pyrin (PYD) and caspase recruitment domain (CARD). Proteins
      containing these domains play pivotal roles in regulating apoptosis and immune
      response pathways. The absence of TMS1/ASC expression in some tumors is because
      methylation of the TMS1/ASC gene contributes to carcinogenesis and cancer
      development. We studied the methylation status of the TMS1/ASC gene and its
      clinical significance in cholangiocarcinoma. METHODS: Target DNA was modified by
      sodium bisulfite, coverting all unmethylated, but not methylated, cytosines to
      uracil, and subsequently by a nested amplification with primers specific for
      methylated versus unmethylated DNA. The PCR product was detected by gel
      electrophoresis and combined with the clinical records of patients. RESULTS:
      Aberrant methylation of the TMS1/ASC gene was detected in specimens of colorectal
      cancer tissues from 13 (36.1%) of 36 patients, and specimens of adjacent normal
      tissues from 3 patients (8.3%). No statistical differences were seen in the
      extent of differentiation and invasion, lymph node metastasis, and pathologic
      type between the methylated and unmethylated tissues (P>0.05). CONCLUSIONS: The
      frequency of TMS1/ASC gene methylation in cholangiocarcinoma is high, but it is
      not related to pathologic changes. The TMS1/ASC gene is probably suppressed by
      methylation, and is resistant to apoptosis and immunological surveillance. The
      gene epigenetically affected in methylated tissues could be associated with
      carcinogenesis of cholangiocarcinoma.

PMID- 16911949
TI  - Diagnosis and treatment of solid-pseudopapillary tumor of the pancreas.
AB  - BACKGROUND: Solid-pseudopapillary tumor (SPT) of the pancreas is a rare exocrine
      pancreatic tumor. Despite the increasing recognition of the tumor in recent
      years, its pathogenesis and apparent therapeutic algorithm remain unclear. This
      study was designed to define the clinical, imaging, and pathologic features and
      to improve the diagnosis and treatment of this rare disease. METHOD: The
      clinical, imaging, and pathologic findings of 9 SPT patients managed in our
      hospital between 2001 and 2005 were retrospectively analyzed, and related
      literatures were reviewed. RESULTS: In the 9 patients aged from 14 to 68 years, 8
      were female and 1 male. The mean age of these patients at diagnosis was 30 years.
      Initially, 8 patients complained of vague abdominal pain and one patient had
      pancreatic mass detected incidentally by abdominal CT. The levels of blood and
      urine amylase and tumor markers were all within the normal range. B-US, CT and
      MRI demonstrated that tumors were well encapsulated and contained some degree of
      internal hemorrhage or cystic degeneration. The mean transverse diameter of these
      tumors was 5.4 cm (range, 2-10.5 cm). The tumors were located at the head (2
      patients), body (2), body and tail junction (4), and tail (1) of the pancreas.
      Surgical procedures included pancreaticoduodenectomy, distal pancreatectomy,
      distal pancreatectomy with splenectomy, and enucleation. Histological examination
      showed solidified cystic areas and papillary protrusions. Two malignant tumors
      demonstrated retroperitoneal metastases and vascular invasion. Follow-up for 2.5
      years on average showed that one patient died of tumor recurrence at 10 months
      and the rest were alive. CONCLUSIONS: SPT exhibits unique clinical and pathologic
      features and is readily diagnosed by its characteristic imaging and histological
      appearance. Surgical resection of the primary tumor and metastases is the
      treatment of choice.

PMID- 16911950
TI  - Diaphragmatic hernia after right donor and hepatectomy: a rare donor complication
      of partial hepatectomy for transplantation.
AB  - BACKGROUND: Because of the critical worldwide shortage of cadaveric organ donors,
      transplant professionals have increasingly turned to living donors. Partial
      hepatectomy for adult living donor liver transplantation has been performed since
      the late 1990s. Most often, the complications of living donor hepatectomy have
      been related to the biliary tract, specifically biliary leaks. METHODS: A 54-year
      old man underwent donor right hepatectomy for living donor liver transplantation.
      Three years after liver donation he presented with upper abdominal pain and
      fullness. Radiographic workup revealed a diaphragmatic hernia of the right
      hemithorax. RESULTS: After thoracoscopic evaluation of the right hemithorax,
      diaphragmatic hernia was repaired. Currently the patient remains well several
      months after the repair with complete resolution of abdominal pain, normal chest
      X-ray examination demonstrating no recurrence of diaphragmatic hernia, and normal
      liver functions tests. CONCLUSIONS: Multiple complications of living donor liver
      transplantation have been described the transplant literature. Diaphragmatic
      hernia is a formerly-undescribed complication of right donor hepatectomy for
      transplantation.

PMID- 16911951
TI  - Cholecystocolocutaneous fistula: a case report.
AB  - BACKGROUND: Cholecystocolocutaneous fistula (CCCF) is a rare complication of
      gallstone disease resulting from spillage of gallstones from perforation of an
      empyema of the gallbladder, which can pose diagnostic dilemmas. We describe a
      patient, who presented initially with a swelling followed by discharging sinuses
      on her right flank where a diagnosis of CCCF was made and was treated surgically
      with satisfactory outcome. METHODS: A computed tomography (CT) scan showed an ill
      defined soft tissue mass in the right subhepatic space and a fistulogram
      demonstrated passage of contrast into the gallbladder fossa and hepatic flexure
      of colon. At laparotomy, a cutaneous fistula containing two pigment stones led to
      the gallbladder fossa and hepatic flexure of colon. RESULTS: Debridement of
      infected granulation tissues which had replaced the gallbladder, closure of the
      cystic duct stump and colonic fistula followed by excision of the fistula tract
      led to complete resolution. CONCLUSIONS: CCCF is a rare complication of
      perforated gallbladder with spillage of calculi, and a fistulogram is helpful in
      establishing the diagnosis. This case highlights the importance of retrieving
      spilled stones following interventions in the gallbladder to prevent the
      complication.

PMID- 16911952
TI  - Large cell neuroendocrine carcinoma of the ampulla of Vater.
AB  - BACKGROUND: Neuroendocrine tumors of the ampulla of Vater are extremely rare, and
      few cases of large cell neuroendocrine carcinoma (LCNEC) of the ampulla have been
      reported. METHODS: A 48-year-old male with obstructive jaundice was admitted to
      our hospital. On examination the patient was found to have a periampullary growth
      and subsequently underwent the Whipple's procedure. RESULTS: Histopathological
      examination and immuno-histochemistry revealed features of LCNEC of the ampulla
      of Vater. The patient developed multiple liver metastases 6 months after
      Whipple's procedure. CONCLUSION: LCNEC of the ampulla of Vater is rare and highly
      aggressive, with a dismal prognosis.

PMID- 16911953
TI  - Hypertriglyceridemic acute pancreatitis in a patient with Sheehan's syndrome.
AB  - BACKGROUND: There is no report on case of severe acute hyperlipidemic
      pancreatitis after treatment of Sheehan's syndrome. METHODS: A 32-year-old female
      patient was diagnosed as having acute hyperlipidemic pancreatitis after treatment
      of Sheehan's syndrome, and treated with diet and lipid-lowering agents in early
      stage. RESULTS: Abdominal pain and fever of the patient resolved within a few
      days. She was subjected to diet and oral lipid-lowering therapy on the 4th day
      after admission. The disease did not recur during the follow-up for more than one
      year. CONCLUSIONS: Estrogen replacement therapy should be prescribed for
      Sheehan's syndrome. The serum level of triglyceride should be monitored and
      treatment should be given to prevent severe acute pancreatitis. Lipid-lowering
      therapy in early stage is the key step towards a complete recovery.

PMID- 16911954
TI  - Malignant nonfunctioning islet cell tumor of the pancreas with intrasplenic
      growth: a case report.
AB  - BACKGROUND: We reported a case of malignant nonfunction islet cell tumor (10.0 cm
      in diameter) of the pancreas, with malignant histological features and splenic
      infiltration. The case is rare, and few reports have been published. METHODS: A
      46-year-old woman with a vague pain in the left upper quadrant for 3 months was
      found to have a tumor in the spleen. Ultrasonography and computed tomography
      demonstrated a well-defined pancreatic tumor of 8.2 X 10.0 cm in size, her serum
      levels of pancreatic hormones were within normal limits. RESULTS: Splenectomy
      combined with pancreatectomy was performed for the tail of the pancreas. Resected
      specimens showed a malignant nonfunctioning islet cell tumor invading the spleen.
      CONCLUSIONS: The growth pattern of the tumor causes malignant features. Resection
      of the tumor should be performed by enucleation, pancreaticoduodenectomy or
      distal pancreatectomy.

PMID- 16911955
TI  - Subcutaneous tunnel and hepatocholangioplasty after resection for intrahepatic
      stones.

PMID- 16911957
TI  - Cyclin-dependent kinase inhibitors in yeast, animals, and plants: a functional
      comparison.
AB  - The cell cycle is remarkably conserved in yeast, animals, and plants and is
      controlled by cyclin-dependent kinases (CDKs). CDK activity can be inhibited by
      binding of CDK inhibitory proteins, designated CKIs. Numerous studies show that
      CKIs are essential in orchestrating eukaryotic cell proliferation and
      differentiation. In yeast, animals, and plants, CKIs act as regulators of the G1
      checkpoint in response to environmental and developmental cues and assist during
      mitotic cell cycles by inhibiting CDK activity required to arrest mitosis.
      Furthermore, CKIs play an important role in regulating cell cycle exit that
      precedes differentiation and in promoting differentiation in cooperation with
      transcription factors. Moreover, CKIs are essential to control CDK activity in
      endocycling cells. So, in yeast, animals, and plants, CKIs share many functional
      similarities, but their functions are adapted toward the specific needs of the
      eukaryote.

PMID- 16911958
TI  - Proteome-scale analysis of biochemical activity.
AB  - During the last 10 years, there has been a large increase in the number of genome
      sequences available for study, altering the way that the biology of organisms is
      studied. In particular, scientific attention has increasingly focused on the
      proteome, and specifically on the role of all the proteins encoded by the genome.
      We focus here on several aspects of this problem. We describe several
      technologies in widespread use to clone genes on a genome-wide scale, and to
      express and purify the proteins encoded by these genes. We also describe a number
      of methods that have been developed to analyze various biochemical properties of
      the proteins, with attention to the methodology and the limitations of the
      approaches, followed by a look at possible developments in the next decade.

PMID- 16911956
TI  - The structure and function of frataxin.
AB  - Frataxin, a highly conserved protein found in prokaryotes and eukaryotes, is
      required for efficient regulation of cellular iron homeostasis. Humans with a
      frataxin deficiency have the cardio- and neurodegenerative disorder Friedreich's
      ataxia, commonly resulting from a GAA trinucleotide repeat expansion in the
      frataxin gene. While frataxin's specific function remains a point of controversy,
      the general consensus is that the protein assists in controlling cellular iron
      homeostasis by directly binding iron. This review focuses on the structural and
      biochemical aspects of iron binding by the frataxin orthologs and outlines
      molecular attributes that may help explain the protein's role in different
      cellular pathways.

PMID- 16911959
TI  - R104H may suppress transthyretin amyloidogenesis by thermodynamic stabilization,
      but not by the kinetic mechanism characterizing T119 interallelic trans
      suppression.
AB  - The tetrameric protein transthyretin (TTR) forms amyloid fibrils upon
      dissociation and subsequent monomer misfolding, enabling misassembly. Remarkably,
      the aggregation of one of over 100 destabilized TTR variants leads to familial
      amyloid disease. It is known that trans-suppression mediated by the incorporation
      of T119M subunits into tetramers otherwise composed of the most common familial
      variant V30M, ameliorates disease by substantially slowing the rate of tetramer
      dissociation, a mechanism referred to as kinetic stabilization of the native
      state. R104H TTR has been reported to be non-pathogenic, and recently, this
      variant has been invoked as a trans-suppressor of amyloid fibril formation. Here,
      we demonstrate that the trans-suppression mechanism of R104H does not involve
      kinetic stabilization of the tetrameric structure, instead its modest trans
      suppression most likely results from the thermodynamic stabilization of the
      tetrameric TTR structure. Thermodynamic stabilization increases the fraction of
      tetramer at the expense of the misfolding competent monomer decreasing the
      ability of TTR to aggregate into amyloid fibrils. As a consequence of this
      stabilization mechanism, R104H may be capable of protecting patients with
      modestly destabilizing mutations against amyloidosis by slightly lowering the
      overall population of monomeric protein that can misfold and form amyloid.

PMID- 16911960
TI  - Photo-induced crosslinking of prion protein oligomers and prions.
AB  - Prion diseases are caused by a unique type of infectious agent, which is thought
      to consist of a misfolded beta-sheeted form of the alpha-helical cellular prion
      protein (PrPC). This misfolded isoform (PrPSc) tends to form insoluble amyloid
      like aggregates, impeding classical structural analysis by X-ray crystallography
      or NMR. Intermolecular crosslinking may provide a means of stabilizing
      notoriously elusive oligomers for further analysis and may be used for analyzing
      aggregate architecture by characterising intermolecular contact sites. Using a
      photo-induced crosslinking method (PICUP), aggregates of recombinant PrP (rPrP)
      and PrPSc were linked at interacting surfaces via amino acid side chains. The
      degree of crosslinking within PrP aggregates was adjustable using varying light
      intensities and could efficiently be monitored by fluorescence correlation
      spectroscopy. Specific intermolecular crosslinking of PrPSc molecules was
      achieved even in crude brain homogenate. Functional studies showed that
      stabilized aggregates of rPrP did not loose their capacity to induce further
      protein aggregation and crosslinking of PrPSc did not alter significantly the
      level of infectivity, indicating that photo-induced covalent linkage of PrPSc
      does not destruct surfaces important for prion propagation.

PMID- 16911961
TI  - Lactadherin binds to elastin--a starting point for medin amyloid formation?
AB  - Medin amyloid is found in the medial layer of the aorta in almost 100% of the
      Caucasian population over 50 years of age. The medin fragment is 5.5 kDa and
      derives from the C2-like domain of the precursor protein lactadherin. We have
      previously reported immunohistochemical findings showing that medin amyloid co
      localizes with elastic fibers of arteries and herein we show that lactadherin
      also is associated with elastic structures of human aortic material. In addition,
      results from in vitro binding assays demonstrate that both medin and lactadherin
      bind to tropoelastin in a concentration-dependent fashion, suggesting that the
      lactadherin-tropoelastin interaction is mediated via the medin domain. It is
      possible that lactadherin, which is a cell adhesion protein, in this way connects
      smooth muscle cells to the elastic fibers of arteries. Given that both medin and
      lactadherin interact with elastic fibers, elastin is probably an important
      component in the formation of medin amyloid.

PMID- 16911962
TI  - Artefactual effects of lipid-based cell transfection reagents on AbetaPP
      processing and Abeta production.
AB  - The study of amyloidogenic beta-amyloid precursor protein (AbetaPP) metabolism
      and amyloid beta protein (Abeta) production has been a major focus of Alzheimer's
      disease (AD) neuropathogenesis research. Cell transfection is a commonly employed
      method for assessing the effects of various genes on AbetaPP processing and Abeta
      production. Certain cell transfection reagents utilize lipid-based formulations
      that could potentially affect AbetaPP processing and Abeta production. Thus, we
      set out to assess the effects of cell transfection reagents with lipid
      formulations (TKO, FuGene6, RNAifect) on AbetaPP processing and Abeta level in H4
      human neuroglioma cells overexpressing human AbetaPP. We found both TKO and
      RNAifect increase the protein levels of AbetaPP-C-terminal fragments (CTFs) and
      Abeta levels, while FuGene6 increases the protein levels of AbetaPP-CTFs without
      altering Abeta level. In contrast, electroporation-based cell transfection does
      not affect AbetaPP processing and Abeta production in our studies. These results
      suggest for the first time that lipid-based cell transfection reagents may
      artefactually affect AbetaPP processing and Abeta production, thereby confounding
      studies aimed at assessing the effects of transfected genes on AbetaPP
      metabolism.

PMID- 16911963
TI  - Analysis of amyloid fibrils in the cheetah (Acinonyx jubatus).
AB  - Recently, a high prevalence of amyloid A (AA) amyloidosis has been documented
      among captive cheetahs worldwide. Biochemical analysis of amyloid fibrils
      extracted from the liver of a Japanese captive cheetah unequivocally showed that
      protein AA was the main fibril constituent. Further characterization of the AA
      fibril components by sodium dodecyl sulphate-polyacrylamide gel electrophoresis
      (SDS-PAGE) and Western blot analysis revealed three main protein AA bands with
      approximate molecular weights of 8, 10 and 12 kDa. Mass spectrometry analysis of
      the 12-kDa component observed in SDS-PAGE and Western blotting confirmed the
      molecular weight of a 12,381-Da peak. Our finding of a 12-kDa protein AA
      component provides evidence that the cheetah SAA sequence is longer than the
      previously reported 90 amino acid residues (approximately 10 kDa), and hence SAA
      is part of the amyloid fibril.

PMID- 16911964
TI  - Value of renal biopsy in the prognosis of liver transplantation in familial
      amyloid polyneuropathy ATTR Val30Met patients.
AB  - Liver transplantation for familial amyloid polyneuropathy (FAP) patients has been
      carried out worldwide and the outcomes seem to be promising. To clarify the
      severity of amyloid deposits on visceral organs, we evaluated the
      histopathological findings of biopsied renal and sural nerve specimens in 13 FAP
      patients with ATTR Val30Met by quantitative analysis, and compared them with the
      outcome of transplantation. Renal dysfunction with proteinuria seemed to
      correlate with the degree of amyloid deposits in glomeruli, not with that in
      medullary tissues. The severity of renal amyloid deposition did not consistently
      parallel that of myelinated nerve fiber loss in sural nerve. Three patients with
      proteinuria and severe amyloid deposits in glomeruli were considered to be
      unsuitable for transplantation. Ten patients underwent living donor liver
      transplantation and three resulted in unfavorable outcomes. These three had heavy
      amyloid deposits on renal tissues, especially in glomerular areas, but the
      severity of myelinated nerve fiber loss in their sural nerves was very similar to
      that in patients who made a good recovery. The prognosis after operation might be
      closely related to the severity of amyloid deposits in renal glomeruli. Renal
      biopsy is, therefore, recommended when determining the indications and
      contraindications for liver transplantation in FAP patients, although this biopsy
      is not routinely required.

PMID- 16911965
TI  - Death during coronary angiography in a woman with cardiac amyloidosis.
AB  - Amyloidosis is a well-recognized systemic disease entity. Patients with cardiac
      amyloidosis have a poor prognosis; the median survival time after development of
      congestive heart failure is 4 months. We describe a 72-year-old woman with
      unsuspected cardiac amyloidosis who died during diagnostic coronary angiography.
      To our knowledge, this is the first report of this complication.

PMID- 16911966
TI  - VIth International Symposium on Familial Amyloidotic Polyneuropathy and other
      Transthyretin Disorders and the Vth International Workshop on Liver
      Transplantation in Familial Amyloidotic Polyneuropathy 24-26 August 2005 La
      Jolla, CA, USA.

PMID- 16911967
TI  - Focusing on beta-amyloid: report of the 35th Annual Meeting of the Society for
      Neuroscience.

PMID- 16911971
TI  - Association between restricted and repetitive behaviors and nonverbal IQ in
      children with autism spectrum disorders.
AB  - The present study explored the relationship between nonverbal IQ and restricted
      and repetitive behaviors (RRBs) in 830 children with Autism Spectrum Disorders.
      The role of chronological age as a moderator of this relationship was also
      investigated. For many behaviors, there was a significant interaction between
      nonverbal IQ and chronological age, such that nonverbal IQ (NVIQ) was more
      strongly related to the prevalence of RRBs in older children. For the majority of
      such behaviors (e.g. repetitive use of objects, hand and finger mannerisms), RRB
      prevalence was negatively associated with NVIQ. However, the prevalence of
      certain behaviors (e.g. circumscribed interests) showed positive relationships
      with NVIQ, which provides some support for the idea of different classes of RRBs.
      For the severity of different RRBs, there were several significant effects for
      age and NVIQ, but few interactions.

PMID- 16911972
TI  - Use of the Mullen Scales of Early Learning for the assessment of young children
      with Autism Spectrum Disorders.
AB  - The psychological assessment is an important component of the diagnostic
      evaluation in young children suspected of having an Autism Spectrum Disorder but
      can be hampered by behavioral difficulties. Overt behaviors during administration
      of the Mullen Scales of Early Learning were coded in 22 preschoolers with an
      Autism Spectrum Disorder and 20 age-matched typically developing children.
      Children in the Autism Spectrum Disorder group required less time to complete the
      assessment but spent proportionally more time exhibiting off-task behaviors and
      less time engaged with the assessment. Scores obtained on the Mullen Scales were
      positively correlated with level of engagement and negatively correlated with off
      task behaviors.

PMID- 16911973
TI  - Neuropsychologic functioning in children with autism: further evidence for
      disordered complex information-processing.
AB  - A wide range of abilities was assessed in 56 high-functioning children with
      autism and 56 age- and IQ-matched controls. Stepwise discriminant analyses
      produced good group discrimination for sensory-perceptual, motor, complex
      language, and complex memory domains but lower agreement for the reasoning domain
      than previously obtained for adults. Group discrimination did not occur for
      attention, simple language, simple memory, and visuospatial domains. Findings
      provide additional support for a complex information-processing model for autism,
      previously based on adult data, demonstrating a pattern across domains of
      selective impairments on measures with high demands for integration of
      information and sparing when demands were low. Children as compared to adults
      with autism exhibited more prominent sensory-perceptual symptoms and less
      pronounced reasoning deficits reflecting brain maturation.

PMID- 16911974
TI  - Neuropsychological characteristics of school-age children with high-functioning
      autism: performance on the NEPSY.
AB  - Utilizing standardization and validation data from the NEPSY, this study presents
      a reanalysis of the High-Functioning Autism (HFA) versus Typical samples using IQ
      as a covariate. The reanalysis in the present paper should prove important to
      clinicians and researchers by (1) determining if the original findings can be
      replicated for the HFA sample when controlling for IQ, and (2) providing
      neuropsychological description for children with HFA versus Typical children
      across the NEPSY variables. The sample included 23 children with HFA who ranged
      in age from 5 years 5 months to 12 years 11 months (Mean = 9.59 years). The HFA
      Group comprised 19 males, 22 Caucasians, and was 87% right handed. All of the
      parents had between 12 to 15 years of education. A Typical Group was selected
      from the standardization sample of the NEPSY and matched on the variables of
      chronological age, race, gender, parental education, and region of the country. A
      MANCOVA revealed significant group differences on 8 of the 14 core subtests of
      the NEPSY, with the HFA Group performing lower than the Typical Group. While
      these findings significantly overlapped with those from the original validation
      study, significant group differences also were uncovered for the subtests of
      Phonological Processing, Auditory Attention and Response Set, and Speeded Naming;
      Comprehension of Instructions and Narrative Memory were no longer significant
      after controlling for IQ. When the groups were compared with respect to the
      number of cases falling below the 10th percentile, the HFA Group showed a higher
      rate of occurrence on each subtest, but only significantly so on the Arrows
      Subtest. These findings provide additional support for the phenotypic
      neurocognitive presentation of individuals with HFA, and they suggest that the
      NEPSY can contribute to the neuropsychological description of children with HFA.

PMID- 16911975
TI  - Analysis of social interaction gestures in infants with autism.
AB  - This study analyzes the emergent use of gestures used among 9-12-month-old
      infants with autism and typical development using retrospective video analysis.
      The purpose of the present investigation was to examine the frequency,
      initiation, prompting, and diversity of types of gestures used for social
      interaction purposes. It was hypothesized that a restricted variety in type(s) of
      gestures as well as fewer child-initiated gestures and more prompted gestures
      would be associated with later diagnosis of autism. Logistic regression analysis
      found that decreased variety in type of gestures used was significantly
      associated with autism status. Neither number of total gestures nor initiation of
      gestures (child-initiated vs. prompted) was significantly associated with autism
      status.

PMID- 16911976
TI  - A comparison of behavioral and emotional functioning in children and adolescents
      with Autistic Disorder and PDD-NOS.
AB  - Behavioral symptomatology was compared in 26 children and adolescents with
      Autistic Disorder ("autism") and 25 children and adolescents with Pervasive
      Developmental Disorder, Not Otherwise Specified ("PDD-NOS"). Relative to
      individuals with PDD-NOS, those with autism had more symptoms of depression,
      social withdrawal, atypical behavior, and immature social skills--and fewer
      family problems. These differences remained even when group differences in
      intellectual ability were statistically controlled. No group differences emerged
      in somatization, anxiety, or hyperactivity. Findings suggest that although both
      groups demonstrate considerable evidence of behavioral and emotional problems,
      those with autism are at particularly high risk for comorbid behavioral and
      emotional disabilities.

PMID- 16911977
TI  - Autism and attention deficit hyperactivity disorder: assessing attention and
      response control with the integrated visual and auditory continuous performance
      test.
AB  - Symptoms of attention deficit hyperactivity disorder (ADHD) have been widely
      reported in children with autism spectrum disorder (ASD). The current study
      investigated attention and response control in children with ASD, ADHD, and
      typical development using the Integrated Visual and Auditory Continuous
      Performance Test. Results indicate that many children with ASD show significant
      deficits in visual and auditory attention and greater deficits in impulsivity
      than children with ADHD or typical development. These findings suggest that many
      of the children with ASD demonstrate significant ADHD-like deficits. These
      findings are discussed in the context of symptoms, subtypes, and comorbidity.

PMID- 16911978
TI  - Response inhibition and immediate arousal in children with high-functioning
      autism.
AB  - The current study compared high-functioning children with autism (HFA) and a peer
      control group on an immediate arousal task measuring response inhibition. In one
      condition go stimuli were presented whereas in another condition a tone preceded
      the go stimulus. The tone caused an immediate arousal effect, which resulted in a
      reaction time decrease and an error rate increase. It was expected that children
      with HFA would produce a higher error rate in comparison with normal peers, since
      they might be less able to suppress immediate arousal. However, the HFA group
      outperformed the control group, indicating neither arousal regulation deficit nor
      response inhibition deficit.

PMID- 16911979
TI  - Exogenous and endogenous attention orienting in autism spectrum disorders.
AB  - Fifteen children with high-functioning Autism Spectrum Disorder (ASD) and 15
      children with typical development completed an attentional cuing task using
      peripheral cues (exogenous orienting) and central cues (endogenous orienting).
      Results showed that participants with ASD had impaired exogenous and intact
      endogenous orienting. The pattern of exogenous orienting was related to motor
      functioning. Individuals with ASD who had poor motor functioning displayed slowed
      exogenous orienting. However, individuals with ASD who had relatively good motor
      functioning showed typical levels of exogenous orienting when given a short time
      but decreased orienting when given a longer amount of time. These results suggest
      attention impairments in ASD may not be specific to social orienting and instead
      may represent a more general orienting impairment.

PMID- 16911980
TI  - Intravitreal triamcinolone acetonide injection for the treatment of posterior
      uveitis.

PMID- 16911981
TI  - Non-invasive detection of multinucleated giant cells in the conjunctiva of
      patients with sarcoidosis by in-vivo confocal microscopy.
AB  - AIM: To explore the use of in-vivo confocal microscopy (IVCM) as a potential non
      invasive adjunctive tool for diagnosing sarcoidosis. METHODS: Conjunctivae were
      imaged using confocal microscopy in 10 patients with sarcoidosis and 27 control
      subjects. We utilized the ASL-1000 Scanning Confocal Microscope (Advanced
      Scanning Ltd., New Orleans, LA) and the Confoscan 3 (Nidek Co. Ltd., Gamagori,
      Japan). Two masked observers reviewed the in-vivo confocal images of the
      conjunctivae in these subjects. One masked observer was experienced in reviewing
      confocal images. The most striking and obvious feature seen in granulomatous
      inflammation on confocal microscopy is the presence of multinucleated giant cells
      (MGCs). RESULTS: Unmasked observation of the scans revealed MGCs in six of the 10
      sarcoid patients and no MGCs in the controls. One experienced masked observer
      found MGCs in five of the 10 patients with sarcoidosis and had no false-positive
      results (Fisher's exact test, p = 0.001; specificity = 1; sensitivity = 50% for
      the diagnosis of sarcoidosis and 83% compared to the unmasked observer). The
      second less-experienced masked observer detected MGCs in three of the 10 patients
      and three of the 27 controls (11.1% of the controls) (p = 0.186; specificity =
      0.89; sensitivity = 30% of all patients with sarcoidosis and 50% compared to the
      unmasked observer). CONCLUSIONS: The utilization of IVCM to visualize the basic
      histology and pathology in sarcoidosis of the conjunctiva is novel. Initial
      results indicate that trained observers can detect MGCs in granulomatous
      inflammation. The ASL-1000 microscope tends to have better resolution and deeper
      penetration of the conjunctiva compared with the Confoscan 3.

PMID- 16911982
TI  - Retinoblastoma: expression of HLA-G.
AB  - PURPOSE: Human leukocyte antigen (HLA) mediates interactions of tumor cells with
      cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. Retinoblastoma (RB)
      is the most common intraocular malignant tumor in childhood and is characterized
      by direct spread to the optic nerve and orbit as well as hematogenous and
      lymphatic spread. Earlier, we observed that invasive RB showed reduced HLA, which
      could contribute to its escape from the immune system. Little is known about the
      role of the nonclassical HLA molecule, HLA-G, in RB and its role in tumor escape
      mechanisms in RB. METHODS: Forty archival paraffin-embedded RB tumors were
      analyzed for the expression of HLA-G by immunohistochemistry using a monoclonal
      antibody; fresh tumor samples were also subjected to Western blot analysis. There
      were 22 tumors with no invasion and 18 with invasion of the choroid/optic nerve.
      Immunoanalysis was performed based on the International Histocompatibility
      Working Group Project Description. RESULTS: HLA-G was negative in the non
      neoplastic retina, reduced in 22/22 tumors with no invasion, and positive in
      15/18 with invasion. The immunohistochemistry results were confirmed by Western
      blot analysis. The difference in expression between the two groups was
      significant ( p < 0.001). There was no correlation of HLA-G expression with
      differentiation of the tumors. CONCLUSION: Increased expression of HLA-G was
      observed in invasive RB. This preliminary observation deserves further
      investigation and may shed more light on the immune escape mechanisms of this
      tumor and thus enable novel therapeutic strategies.

PMID- 16911984
TI  - Pattern of childhood-onset uveitis in a referral center in Tunisia, North Africa.
AB  - PURPOSE: To analyze the pattern of childhood uveitis in a referral center in
      Tunisia, North Africa. METHODS: The study included 64 patients with uveitis
      examined at the Department of Ophthalmology of Monastir (Tunisia) from January
      1994 to July 2005. All patients had a comprehensive ocular and systemic history,
      including an extensive review of medical systems. Complete ophthalmic examination
      was performed in all cases, including best-corrected Snellen visual acuity, slit
      lamp examination, applanation tonometry, and dilated fundus examination with 3
      mirror lens. Standard diagnostic criteria were employed for all syndromes or
      entities of uveitis. RESULTS: The mean age at onset of uveitis was 12.4 years.
      The male-to-female ratio was 0.68. The process was unilateral in 51.6% of
      patients. Mean follow-up was 43.2 months. Anterior and intermediate uveitis each
      represented 31.25% of cases, posterior uveitis 20.3%, and panuveitis 17.2%.
      Noninfectious uveitis (75%) was the most frequent type of inflammation.
      Idiopathic uveitis was found in 50% of patients. Infectious uveitis was
      responsible for 25% of the cases, with toxoplasmosis (14.1%) being the most
      frequent cause. Twenty percent of the patients had systemic associations;
      juvenile idiopathic arthritis was found in 6.25%. Ocular complications occurred
      in 74.7% of affected eyes, of which the most common were posterior synechiae
      (28.4%), cataract (17.9%), cystoid macular edema (19%), and optic disc edema
      (32.6%). Fifty-seven affected eyes (60%) had a final visual acuity more than
      20/40 and nine (9.5%) had a final visual acuity less than 20/200. CONCLUSIONS: In
      a hospital population in Tunisia, a specific cause of uveitis in children was
      found in half the patients. Idiopathic intermediate uveitis was the leading cause
      of uveitis in our study, followed by idiopathic anterior uveitis and
      toxoplasmosis. Uveitis associated with juvenile idiopathic arthritis was rare.
      Visual prognosis appeared to be good.

PMID- 16911983
TI  - In-vitro effects of dexamethasone on cellular proliferation, apoptosis, and Na+
      K+-ATPase activity of bovine corneal endothelial cells.
AB  - PURPOSE: To assess the in-vitro effects of dexamethasone (DEX) on the
      proliferation, apoptosis, and Na+-K+-ATPase activity of bovine corneal
      endothelial cells. METHODS: Bovine corneal endothelial cells were cultured with
      DEX ranging from 10-10 to 10-3 M. The effect of DEX on the proliferation was
      analyzed by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxy-methoxyphenyl)-2-(4
      sulfophenyl)-2H-tetrazolium inner salt (MTS) assay. Apoptosis and necrosis were
      detected by staining with fluorescein-conjugated annexin V and propidium iodide,
      followed by flow cytometry. The effect of DEX on Na+-K+-ATPase activity was
      evaluated using non-isotopic methods. RESULTS: DEX did not affect cellular
      proliferation or induce apoptosis/necrosis from 10-10 to 10-5 M. At 10-4 and 10-3
      M, DEX significantly decreased proliferation and increased apoptosis and/or
      necrosis. DEX significantly increased the Na+-K+-ATPase activity from 10-8 to 10
      6 M, with the maximal effect at 10-6 M (p < 0.01); this effect was inhibited by
      RU38486, an antiglucocorticoid molecule. CONCLUSIONS: Bovine corneal endothelial
      cells express glucocorticoid receptor (GR) mRNA and protein. DEX decreases cell
      proliferation and induces cellular apoptosis and/or necrosis at high
      concentrations. DEX also increases the Na+-K+-ATPase activity at certain
      concentrations.

PMID- 16911985
TI  - Intravitreal triamcinolone acetonide injection for the treatment of posterior
      uveitis.
AB  - PURPOSE: To assess the efficacy and complications of intravitreal triamcinolone
      acetonide (IVTA) injection in the treatment of posterior uveitis and to compare
      the outcomes with patients who had received systemic corticosteroids. METHODS:
      This prospective, interventional, clinical case series study included 11 eyes of
      9 patients who received 8 mg/0.2 ml of IVTA injection for posterior uveitis that
      involved vitreous inflammation (group 1). Control group (group 2) consisted of 15
      eyes of 12 patients who had received systemic corticosteroids for treatment of
      posterior uveitis with vitreous inflammation. The main outcome measures included
      best-corrected visual acuity, vitreous inflammation score and intraocular
      pressure. RESULTS: In group 1, mean visual acuity improved significantly (P <
      0.001) from a mean logarithm of the minimum angle of resolution (LogMAR) value of
      2.05 +/- 0.82 at baseline to a maximum of 0.33 +/- 0.22 during the follow-up
      period of 5.0 +/- 2.8 months. In control group, mean LogMAR visual acuity before
      systemic corticosteroid therapy was 1.82 +/- 0.78, and it has reached a maximum
      of 0.40 +/- 0.22 after treatment (P < 0.001). The mean inflammatory scores
      decreased significantly in both groups when compared with preinjection values
      (for each, P < 0.05). There were no statistically significant differences between
      group 1 and group 2 when pre-and posttreatment visual acuities and inflammatory
      scores at 1-, 3-, and 5-month follow-up examinations were compared (for each, P >
      0.05). In group 1, mean intraocular pressure (IOP) increased significantly from
      13.4 +/- 2.6 mmHg to a mean maximal value of 19.3 +/- 4.3 mmHg (P < 0.001), but
      there was no statistically significant difference between mean IOP at 5-month
      after IVTA injection and pretreatment value (P = 0.06). Cataract progression was
      observed in one eye. CONCLUSIONS: IVTA application may be an alternative
      therapeutic option for the treatment of acute posterior uveitis that involves
      vitreous inflammation, especially in patients who carry risks for systemic
      corticosteroid therapy.

PMID- 16911986
TI  - Recurrent nodular scleritis preceding an adult TINU syndrome.
AB  - PURPOSE: To describe the occurrence of nodular scleritis in a patient developing
      tubulointerstitial nephritis and uveitis (TINU) syndrome. DESIGN: Observational
      case report. METHOD: The case notes of a 57-year-old female presenting with
      recurrent nodular scleritis, who later developed interstitial nephritis with
      bilateral uveitis, were reviewed. RESULTS: Common and established causes of
      scleritis were not present in an adult who developed the TINU syndrome a decade
      later. CONCLUSIONS: Although scleritis has not been reported as a
      tubulointerstitial nephritis-associated ocular inflammation, it may be part of
      the possible spectrum of ocular inflammation occurring as part of the TINU
      syndrome.

PMID- 16911987
TI  - Dendritiform cells found in central cornea by in-vivo confocal microscopy in a
      patient with mixed bacterial keratitis.
AB  - PURPOSE: To report the in-vivo confocal microscopic findings of dendritiform
      cells in the central corneal epithelial layer in a case of mixed bacterial
      keratitis associated with severe immunologic reaction. DESIGN: Observational case
      report. METHODS: A 25-year-old male suffered from contact lens-related mixed
      bacterial keratitis with a dense eccentric immune ring. In-vivo confocal
      microscopy was performed to study the different layers of the central and
      peripheral cornea in the lesion and the fellow eye. RESULTS: Several dendritiform
      cells were found in the basal and superficial epithelial layers of the central
      cornea in the lesion eye, which was also the area of the dense immune ring
      formation. No such cells could be identified in the fellow eye or the unaffected
      area of the lesion eye. CONCLUSION: Corneal dendritiform cells, possibly
      dendritic or Langerhans cells, can be identified in severe corneal immunologic
      conditions using in-vivo confocal microscopy. The role of these cells in ocular
      immunity is interesting and needs further clarification.

PMID- 16911988
TI  - Retinal pigment epithelial detachment in sarcoidosis.
AB  - PURPOSE: To report primary retinal pigment epithelial (RPE) detachments in
      sarcoidosis. DESIGN: Case report. METHODS: Clinical findings, fluorescence
      angiography and optical coherence tomography (OCT) results are presented and
      discussed. RESULTS: A 54-year-old Hispanic male with biopsy proved sarcoidosis
      presented with multiple RPE detachment in both eyes. Except for acute iritis,
      there were no other ocular manifestations of sarcoidosis. CONCLUSIONS:
      Detachments of the RPE may be a rare manifestation of ocular sarcoidosis.

PMID- 16911991
TI  - Sagittal synostosis: I. Preoperative morphology of the skull.
AB  - The aim of this study was to characterise the preoperative morphology of the
      skull in sagittal synostosis in an objective and quantified way. The shapes of
      the skulls of 105 patients with isolated premature synostosis of the sagittal
      suture (SS group) were studied and compared with those of a control group of 72
      children with unilateral incomplete cleft lip (UICL). A standardised
      radiocephalometric technique was used to obtain the images. A modification of a
      method developed by Kreiborg was used to analyse the radiocephalograms, which
      included the digitisation of 88 landmarks in the calvaria, skull base, and orbit
      (42 in the lateral and 46 in the frontal projections), the production of plots of
      mean shape for each group, and the intergroup comparison of a series of 81
      variables (linear distance between selected landmarks, and angles defined by
      groups of three landmarks). Data from a subgroup of 66 patients aged 5 to 8
      months were further compared to age-matched normative data in terms of seven
      angular and linear calvarial, cranial base and orbital variables. In a
      comparative analysis of the mean lateral plots, the foreheads of the study group
      (SS) had a more pronounced anterior slope and were also more convex. The vertex
      area was located more anteriorly, and was less convex. The occipital curvature
      was more prominent. Analysis of the mean frontal plots revealed a lack in
      convexity and lateral projection of the upper parietal regions, as well as a
      lower location of the line of maximum skull width. Comparison of the mean values
      of an SS subgroup to age-matched normative data showed a longer (p<0.001) and
      narrower skull (p<0.001) and a greater interorbital distance (p<0.001). The
      cranial base angle, the sella to nasion, and sella to basion lengths did not
      differ significantly. Sagittal synostosis is characterised by an extensive
      deformity of the cranial vault, with an essentially normal cranial base. The
      widened interorbital distance is probably related to compensatory metopic
      hyperactivity.

PMID- 16911989
TI  - Subretinal abscess due to Nocardia farcinica resistant to trimethoprim-
      sulfamethoxazole in a patient with systemic lupus erythematosus.
AB  - PURPOSE: To report a case of subretinal abscess due to Nocardia farcinica
      resistant to trimethoprim-sulfamethoxazole in a patient with systemic lupus
      erythematosus on immunosuppressive therapy. DESIGN: Observational case report.
      METHODS: We retrospectively studied the medical record of a patient with
      nocardiosis. RESULTS: The microorganism disseminated from the lungs (pneumonia)
      to the eye and brain. The ocular lesion appeared to be a yellowish, lobulated
      subretinal abscess with irregular surface and superficial retinal hemorrhages. As
      it was not responding to empiric therapy for nocardia, pars plana vitrectomy and
      aspiration of the subretinal material was performed to confirm the etiology.
      CONCLUSION: In an immunocompromised patient with pulmonary involvement and a
      subretinal abscess with a characteristic aspect, one should consider nocardia as
      a possible etiology taking into account its possible antibiotic resistances.

PMID- 16911992
TI  - Sagittal synostosis: II. Cranial morphology and growth after the modified pi
      plasty.
AB  - The aim of this study was to characterise the postoperative cranial growth and
      morphology after a modified pi-plasty for sagittal synostosis. The shape of the
      skull of 82 patients with isolated premature synostosis of the sagittal suture
      (SS group) operated on with a modified pi-plasty was studied longitudinally.
      Forty-five children with unilateral incomplete cleft lip (UICL), evaluated
      longitudinally at the ages of 2.4 and 23.2 months were used as controls. A
      standardised radiocephalometric technique was used for image acquisition. The
      radiocephalograms were analysed using a modification of a method developed by
      Kreiborg, which included the digitisation of 89 landmarks of the calvaria,
      cranial base, and orbit (43 in the lateral and 46 in the frontal projections),
      the production of mean shape plots for each group, and the intergroup comparison
      of a series of 78 variables (linear distance between selected landmarks, and
      angles defined by groups of three landmarks). Paired and unpaired t tests were
      used to assess the differences between the variables studied. These were accepted
      as significant for values of p<0.01 and were presented as coloured segments or
      areas in the respective plots. In a comparative analysis with the mean UICL
      lateral plots, the mean preoperative lateral plots of the study group (SS) showed
      that the anterior slope of the forehead was more pronounced and it was also more
      convex. The vertex area was located more anteriorly and was less convex. The
      occipital curvature was more prominent. Comparison of the mean frontal plots
      showed a deficiency in convexity and lateral projection of the upper parietal
      regions, and the line of maximum skull width was lower. The postoperative mean
      lateral plots of the study group showed a correction of the exaggerated anterior
      inclination of the forehead and a reduction of the abnormal occipital convexity.
      However, there was little change in the vertex region and it remained flatter
      than in the control group. In the mean frontal plots, the increase in convexity
      and in the lateral projection of the upper parietal areas led to a shape that was
      similar to that of the UICL group. The mean (SD) cephalic index changed from
      64.9% (1.8%) to 71.4% (3.5%) (p<0.001). The longitudinal comparison between the
      mean postoperative plots at 3 and 5 years of age showed that there had been
      little change in cranial shape. In conclusion, after a modified pi-plasty for
      sagittal synostosis, significant objective changes in cranial shape towards
      normality were produced. The postoperative profile cranial shape was improved
      except in the vertex area, which remained flatter than normal. In the frontal
      projection an almost normal shape was obtained. The postoperative cranial shape
      obtained at 3 years of age had remained stable at the age of 5 years.

PMID- 16911993
TI  - Combined repair of lip and palate with pharyngoplasty for late presenting clefts.
AB  - A combined lip and palatal repair with an Orticochea sphincter repair was done in
      nine patients presenting to our cleft team in Nepal and Tibet for the first time
      after the age of 8 years. This retrospective study assessed the procedure using
      the outcome measurements of operative morbidity and postoperative nasality and
      intelligibility of speech. The total median postoperative hospital stay was 2
      days (range 1-4). There were no intraoperative or in-hospital complications. One
      patient developed a small fistula. Speech results were available in only four of
      the patients. Nasality was mild in two, moderate in one, with mixed hypernasality
      and hyponasality in one patient. Intelligibility was very good in one, fair in
      two, and poor in one. Combined lip and palatal repair with pharyngoplasty is a
      safe procedure in patients over the age of 8. Speech outcomes in those who came
      for follow-up were satisfactory.

PMID- 16911994
TI  - Orthopaedic POSSUM scoring system: an assessment of the risk of debridement in
      patients with pressure sores.
AB  - We hypothesised that the implementation of a validated method of audit, the
      Physiological and Operative Severity Score for enUmeration of Mortality and
      morbidity (POSSUM), would be useful in the evaluation of the risks of debridement
      in bedridden patients with pressure ulcers. With the orthopaedic version of
      POSSUM (O-POSSUM), physiological data and an operative profile are scored to
      predict mortality for 30 days postoperatively. Fourteen cases were analysed
      retrospectively. The difference in predicted mortality was compared with those
      who died and those who survived. The mean (SD) predicted mortality among those
      who died was 47 (16)%, and among those who lived was 18 (14)%. Those who died
      were classified as a relatively high risk group, and the values differed
      significantly (p=0.01). O-POSSUM may be helpful in audit.

PMID- 16911995
TI  - Comparison of assessment tools to score recovery of function after repair of
      traumatic lesions of the median nerve.
AB  - In this paper the recovery after repair of the median nerve has been used to
      compare different assessment tools for evaluation of peripheral nerve function:
      touch (moving 2-point discrimination (2PD); Semmes-Weinstein (SW) monofilament,
      motor (Medical Research Council (MRC) scale), combined motor and sensory (Dellon
      modification of the Moberg pick up test; Moberg Recognition test), and pain
      (visual analogue scale; pinprick-test). The mean (SD) age of our 28 patients was
      28 (12) years. The mean (SD) follow-up period was 5 years, 2 months (2 years, 8
      months). On the operated side three patients (11%) had a moving 2PD of less than
      4 mm. The results of the moving 2PD were compared with those of the SW
      monofilaments, but with a poor correlation. The MRC score correlated well with
      opposition movement of the thumb and muscle wasting (p<0.01). We recommend a
      number of tests to evaluate (the chronological return of) peripheral nerve
      function.

PMID- 16911996
TI  - Efficacy and safety of axillary brachial plexus block for operations on the hand.
AB  - An axillary brachial plexus nerve block by a transarterial approach is commonly
      used to achieve regional anaesthesia for hand surgery. We designed a
      retrospective study to evaluate efficacy and safety of the technique for acute
      and elective operations. Anaesthetic records of 189 of all 5520 patients (1996
      2000) who had axillary brachial plexus blocks for hand surgery were reviewed, and
      results compared with complications recorded in the anaesthetic register and in
      the hand surgery records. Successful axillary block was achieved in 5128/5520
      (93%) of patients, according to anaesthetic charts, and primarily in 157/189
      (83%), and after supplementation in 171/189 (90%), according to anaesthetic
      records. Four patients had a toxic drug reaction or axillary haematoma with a
      transient neurological deficit. Medical complications were recorded in the
      anaesthetic register in less than 0.7% of axillary brachial plexus procedures.
      Axillary brachial plexus block by a transarterial approach is effective and safe
      in hand surgery.

PMID- 16911997
TI  - Range of movement in the wrist as a diagnostic tool in radial-sided wrist pain.
AB  - Kienbock disease is diagnosed by imaging studies, and is often difficult to
      diagnose in its early stages. Our clinical impression is that wrist movement is
      more limited in Kienbock disease than when radial-sided wrist pain is caused by
      other conditions. The purpose of this study was to determine the use of wrist
      movement in differentiating between early Kienbock disease and radial-sided
      sprained wrist. We retrospectively reviewed 62 cases of Kienbock disease and 49
      patients with radial-sided wrist sprain. Wrist movement at presentation was
      recorded. The two groups differed significantly in flexion and extension
      (p<0.001). The ability of movement of the affected wrist relative to the normal
      side to distinguish between the groups was excellent (AUC = 0.96, 0.97,
      respectively). The ability of wrist movement measurements to differentiate
      between early Kienbock disease and radial-sided wrist sprain emphasises that
      wrist movement should be measured prior to invasive or expensive testing.

PMID- 16911998
TI  - Functional magnetic resonance imaging shows cortical activation on sensory
      stimulation of an osseointegrated prosthetic thumb.
AB  - Functional magnetic resonance imaging (fMRI) was used to study the cortical
      integration of an osseointegrated prosthetic thumb that had been attached to the
      amputee's hand 13 years ago. We found that tactile stimuli applied to the
      prosthesis activated the primary somatosensory cortex on both sides.

PMID- 16911999
TI  - Vascularised bone graft for the treatment of non-union of the scaphoid.
AB  - A 4/5 compartment pedicled vascularised bone graft from the distal radius
      combined with internal fixation with a Herbert type cannulated screw was used to
      treat non-union fractures of the proximal pole of the scaphoid in 13 patients.
      Non-union was identified on plain radiographs alone. Uneventful clinical and
      radiological healing was achieved in 11 patients. One patient had progressive
      signs of failure of the fixation of the screw at the proximal pole; the screw was
      changed and the fracture was stable at reoperation. One patient had a fall
      postoperatively, radiographs taken at follow-ups showed only partial healing, and
      he had a bone graft 12 months later. Twelve patients had clinical and
      radiological union of the fracture, and one patient fibrous healing alone. The
      technique may improve healing of non-union of fractures of the proximal pole of
      the scaphoid, but it is still a technical challenge.

PMID- 16912000
TI  - Fixation of intracapsular fractures of the condylar head with bioabsorbable
      screws.
AB  - A newly-developed fixation technique using bioabsorbable screws gave satisfactory
      results in fractures of the condylar head. The fracture lines ran obliquely
      (craniolateral to mediocaudal) on three-dimensional computed tomography. Two
      bioabsorbable screws were positioned vertically to the fracture lines. This
      technique is useful despite limited access to the condyle.

PMID- 16912001
TI  - Ectopic hamartomatous thymoma growing in the sternocleidomastoid muscle
      masquerading as sarcoma.
AB  - The distinction between ectopic hamartomatous thymoma and sarcoma is difficult,
      and preoperative biopsy and intraoperative histopathological examination fail to
      give a definitive diagnosis. It is important to recognise ectopic hamartomatous
      thymoma as one of the differential diagnoses of a cervical tumour.

PMID- 16912002
TI  - Japanese family with Greig cephalopolysyndactyly syndrome, including bilateral
      seven toes, and esotropia, over three generations.
AB  - We report a Japanese family with Greig cephalopolysyndactyly syndrome (GCPS), in
      which the grandmother, mother, and daughter were affected. They each had the same
      characteristics including bilateral seven toes, hypertelorism, and esotropia.
      Bilateral seven toes and esotropia had followed over three generations and have
      not previously been reported in this syndrome. The present case with bilateral
      seven toes and esotropia may be a new type.

PMID- 16912003
TI  - Recent advances in mental health services research. Introduction.

PMID- 16912004
TI  - The political evolution of mental health parity.
AB  - This article traces the evolution of the mental health parity debate in American
      politics, with a focus on how interest groups and politicians have attempted to
      influence perceptions about treatment effectiveness and the cost of benefit
      expansion. When parity laws are in place, they require health plans operating in
      the private health insurance market to provide an equivalent level of coverage
      for mental health and general medical care. Business and insurance industry
      groups oppose parity due to cost concerns. The mental health community has framed
      parity as an antidiscrimination measure that would achieve greater insurance
      equity across disease groups. The role of personal experience with mental illness
      among lawmakers and others in framing the parity debate is also considered.

PMID- 16912005
TI  - Of treatment systems and depression: an overview of quality-improvement
      opportunities in hospital-based psychiatric care.
AB  - A clinical perspective on depression tends to focus on therapy and on medications
      or psychological interventions that may be helpful to individual patients. A
      broader view on the treatment enterprise, however, suggests that there are other
      dimensions to treatment and that opportunities for improving the quality of care
      and patient outcomes are not limited to innovation in therapeutics. This article
      examines several of the nonclinical facets of inpatient care, using the frame of
      a conceptual pyramid to explore the relationships between therapy and its
      professional, organizational, care-management, and economic concomitants. By
      drawing on a conceptual pyramid that elucidates several nonclinical dimensions of
      inpatient treatment for depression, we describe the potential for corresponding
      quality improvement activities among psychiatric providers. The pyramid suggests
      that there are multiple opportunities for future interventions to promote quality
      in inpatient psychiatric care, that those opportunities are considerably more
      varied than a purely clinical perspective might recognize, and that interventions
      in nonclinical aspects of the treatment system have the potential to cascade
      "downward" to affect clinical outcomes over time.

PMID- 16912006
TI  - Medical errors in psychiatry.
AB  - Medical errors in the general medical sector result in significant patient deaths
      and injuries, as well as high costs to the health care system. Despite the
      growing literature on errors in medical and surgical specialties, few studies
      have examined the incidence, nature, predictors, and prevention of errors that
      may occur in mental health treatment settings. The purpose of the current review
      is to examine the lessons learned from patient-safety research in the general
      medical sector, provide examples of types of errors in psychiatry, review the
      errors identified in the literature, offer a discussion of error-reduction
      strategies for improving patient safety, and provide recommendations for future
      research. Increased attention to medical errors in psychiatry is necessary in
      order to build safer health systems and promote a culture of safety among
      providers, thereby producing better care for patients with mental disorders.

PMID- 16912007
TI  - Cigarette smoking and overweight/obesity among individuals with serious mental
      illnesses: a preventive perspective.
AB  - BACKGROUND: Cigarette smoking and lifestyle factors underlying overweight/obesity
      (such as unhealthy diet and physical inactivity) appear to play a major role in
      the excess medical morbidity and mortality among persons with serious mental
      illnesses. The literature on the prevalence, etiology, prevention, and treatment
      of these two risk factors, in the context of serious mental illnesses, are
      reviewed following a preventive approach. METHODS: The review relied upon
      searches of the MEDLINE database, from 1996 through April 2006, restricted to the
      English language. Original research, review articles, and clinical guidelines
      relevant to the topics of cigarette smoking, unhealthy diet, physical inactivity,
      and overweight/obesity among individuals with serious mental illnesses were
      identified. RESULTS: Compared to those without a mental illness, individuals with
      a current mental illness are more than twice as likely to smoke cigarettes and
      more than 50% more likely to be overweight/obese, presumably the product of
      unhealthy diet and physical inactivity. Various biological, iatrogenic, and
      social factors place psychiatric patients at risk for these and other adverse
      health behaviors. Studies suggest that many of the same preventive approaches
      developed for general medical populations are likely to be effective in persons
      with serious mental disorders, though specialized approaches also are needed.
      Domains of prevention include primary prevention (population-based strategies to
      reduce the incidence of these adverse health behaviors), secondary prevention
      (early detection and treatment), and tertiary prevention (pharmacological and
      psychosocial treatments to reduce the burden of illness among those with the
      behaviors in question). However, mental health clinicians commonly lack the
      training or expertise to provide these services. CONCLUSIONS: The high
      prevalence, adverse effects, and efficaciousness of treatments for smoking and
      obesity in persons with serious mental illnesses suggest the importance of
      addressing these problems in this population. Both further research and
      dissemination efforts are needed to ensure that patients with serious mental
      illnesses receive the appropriate preventive and clinical services for these two
      adverse health conditions.

PMID- 16912008
TI  - Welfare reform, employment, and drug and alcohol use among low-income women.
AB  - In 1996 welfare reform legislation transformed income assistance for needy
      families by imposing work requirements, time-limited benefits, and explicit
      provisions allowing states to sanction recipients who fail to meet program
      requirements. Though they represent a minority of the welfare population, women
      with substance use disorders (SUDs) experience multiple, and more severe,
      employment barriers than other Temporary Assistance to Needy Families (TANF)
      recipients. This review of welfare reform, substance abuse, and employment
      documents the evidence to date regarding the employment patterns of women with
      SUDs before and after welfare reform, and proposes several topics for further
      research. Based on higher rates of unemployment, less work experience, and lower
      earnings when working, women with SUDs have worse employment records than other
      TANF recipients. Despite elevated employment barriers, women with SUDs left TANF
      after 1996 as fast as, or faster than, other women. Since the 1996 welfare
      reform, women with SUDs have increased their employment and earnings, but by less
      than similar women without SUDs. Future research should describe how specific
      state welfare policies relate to employment of low-income women with SUDs, how
      the well-being of these women and their children changes with employment, and how
      welfare and employment interact to affect access to health insurance among this
      population.

PMID- 16912009
TI  - Anterior visual pathway gliomas: The last 30 years.
AB  - Modern neuroimaging provides excellent characterization of anterior visual
      pathway gliomas, often obviating the need for biopsy of the tumor. Management
      remains controversial, but if there is progression, chemotherapy is preferred for
      young patients. Stereotactically guided conformal radiotherapy and proton beam
      radiotherapy allow smaller, more precise doses of radiation to be administered
      and can be considered in older children with progressive disease. A mouse model
      of NF-1 with optic pathway gliomas has the potential to provide important
      insights into the development of gliomas as well as serving as a model for their
      effective treatment.

PMID- 16912010
TI  - Primary intraocular lymphoma: A review.
AB  - Primary intraocular lymphoma (PIOL) is a type of primary central nervous system
      lymphoma (PCNSL). It is the most common neoplastic masquerade syndrome involving
      the eye. Its protean ocular manifestations, plus in many cases the initial
      positive response to corticosteroid therapy for presumed uveitis, delay accurate
      diagnosis. A high index of suspicion is essential, followed by tissue biopsy with
      cytology and ancillary studies. Current treatment is based on chemotherapy
      featuring high-dose methotrexate and radiation therapy. Prognosis is poor due to
      CNS involvement, but newer therapies have had some success in prolonging
      survival.

PMID- 16912011
TI  - Cancer associated retinopathy (CAR): An autoimmune-mediated paraneoplastic
      syndrome.
AB  - Cancer associated retinopathy (CAR) is an uncommon paraneoplastic retinopathy in
      which antibodies are directed against retinal antigens. Vision loss is associated
      with abnormal ERG findings. Few case reports and lack of controlled clinical
      trials make management of this syndrome especially challenging for the clinician.
      Herein, we describe the clinical, histopathologic and electrophysiologic features
      of CAR, along with a summary of previously employed management options. Cancer
      associated retinopathy syndrome has been recognized as a paraneoplastic disorder,
      most commonly associated with small cell lung cancer, in which cross-reacting
      autoantibodies against retinal antigen cause retinal dysfunction. Bilateral
      vision loss as a result of both rod and cone dysfunction in CAR may occur over a
      period of months, and visual symptoms may precede diagnosis of the systemic
      malignancy. The heterogeneity in antigens that have been identified as targets of
      antibody-mediated retinal damage perhaps help to explain the complexity of
      symptoms and the treatment challenges posed by patients with CAR.

PMID- 16912013
TI  - Anti-angiogenic therapy: Prospects for treatment of ocular tumors.
AB  - The growth of new blood vessels (angiogenesis) within tumors is essential for
      tumor growth, maintenance, and metastasis. Angiogenesis research has identified a
      host of pro- and anti-angiogenic factors that regulate an "angiogenic switch,"
      which when turned on, allows tumors to assume a more aggressive form. Angiogensis
      inhibitors that target this switch are in clinical trials for a wide array of
      tumor types. Although angiogenesis inhibitors are already widely used to treat
      ocular disease, only limited case reports are currently available for the use of
      angiogenesis inhibitors to treat ocular tumors. Evidence for angiogenesis in the
      growth and spread of uveal melanoma, retinoblastoma, and von Hippel Lindau (VHL)
      disease exists. The very limited trials of angiogenesis inhibitors in the
      treatment of uveal melanoma and VHL are promising, although more extensive
      controlled trials will be needed to confirm their efficacy.

PMID- 16912012
TI  - Retinal capillary hemangiomas and von Hippel-Lindau disease.
AB  - von Hippel-Lindau disease is a multisystem familial cancer syndrome that commonly
      manifests in the eye as retinal capillary hemangiomas. As the earliest
      manifestation of the disease, these benign hamartomas can lead to secondary
      visual loss. Their typical clinical characteristics can lead to accurate
      diagnosis and appropriate treatment with either laser photocoagulation or
      cryotherapy enhancing one's probability of preserving vision before becoming
      symptomatic. Accurate diagnosis can also lead to surveillance of the various
      other organ systems involved in the disease such as the CNS, kidneys, adrenal
      glands and pancreas. This will also enable the clinician to provide genetic
      counseling for patients regarding the lifelong manifestations of this disease.

PMID- 16912014
TI  - Topical medical therapies for ocular surface tumors.
AB  - We review the use of three topical medications for the therapy of ocular surface
      tumors: mitomycin C, 5-fluorouracil, and interferon alpha-2B. One hundred sixty
      patients with histologically or cytologically proven epithelial and melanocytic
      tumors were identified in the literature. Side effects occurred most often with
      mitomycin C, followed by 5-fluorouracil, and interferon alpha-2B. Patients most
      frequently experienced transient keratitis, redness, and irritation. Topical
      agents were used as both primary and adjuvant therapy. Rates of tumor regression
      for CIN and squamous cell carcinoma ranged from 80 to 96%, and 70% of pigmented
      tumors regressed after an average follow-up of 27 months.

PMID- 16912015
TI  - Radiotherapy and cataract formation.
AB  - In the past five decades, the treatment options for intraocular tumors have
      expanded from one surgical option of enucleation to numerous regimens including
      radiotherapy. Radiotherapy has proven to be as efficacious in controlling the
      malignant lesion; however, normal ocular structures can also be affected. The
      lens is radio-sensitive and therefore the development of post radiation cataract
      commonly impairs vision and the ability to monitor tumor recurrence. Prevalence,
      severity, onset, and prognosis of radiation-induced cataract depend highly on the
      dose and rate of radiation. Recently, additional studies have given insight into
      this important relationship and the efficacy of treatment options.

PMID- 16912016
TI  - Glaucomas secondary to intraocular melanomas.
AB  - Intraocular melanomas are not common entities but often lead to secondary
      glaucoma. Intraocular melanomas should be considered in the differential
      diagnosis of patients with unilateral glaucoma. Occasionally, the workup of
      unilateral glaucoma leads to a diagnosis of an intraocular melanoma. Intraocular
      melanomas represent the majority of intraocular tumors. The prevalence of
      intraocular melanomas as well as associated secondary glaucomas will be reviewed.
      The workup needed for unilateral glaucoma will be covered in detail. Treatment
      options for secondary glaucomas include topical and oral medications as well as
      argon laser trabeculoplasty and transscleral cyclophotocoagulation.

PMID- 16912017
TI  - Glaucoma in juvenile xanthogranuloma.
AB  - Juvenile xanthogranuloma (JXG) is a benign histiocytic skin disorder mainly
      encountered during infancy. Approximately 10% of cases exhibit ocular
      manifestations leading to serious complications. Specifically, secondary glaucoma
      can result in severe and blinding eye disease. We present a case of a two-month
      old female with JXG related glaucoma in order to demonstrate the classic
      presentation and the problems commonly encountered in treating this disease. The
      natural history, pathogenesis, and treatment of the condition are then discussed
      and the pertinent literature reviewed. JXG should be considered in any case of
      unilateral glaucoma that presents in infancy.

PMID- 16912018
TI  - Cutaneous melanomas of the eyelid.
AB  - Cutaneous eyelid melanomas are very rare lesions. The lentiginous subtypes are
      the most frequent melanocytic lesions of the eyelid and can be likened to
      conjunctival melanocytic lesions like PAM, PAM with atypia and conjunctival
      melanoma. Compared to melanomas elsewhere on the body, eyelid melanomas have
      special considerations. Eyelid skin is very thin, the mucocutaneous junction at
      the lid margin can affect prognosis, the lymphatic drainage pattern is very
      variable and there is an inherent difficulty to excise wide margins without
      sacrificing important structures. A customized excision approach, using tissue
      sparing "Slow-Mohs" technique, is suggested. Sentinel lymph node dissection has
      an evolving therapeutic role but remains controversial.

PMID- 16912019
TI  - Orbital dermoids in children.
AB  - Orbital dermoid cysts are benign congenital choristomas. They are common in
      pediatric population, developing adjacent to suture lines, most commonly located
      in antero-lateral fronto-zygomatic suture, and are slowly progressive. Complete
      surgical excision without rupture of cyst is the standard of care. Deep orbital
      cysts cause proptosis, require imaging, and may present a surgical challenge with
      a difficult approach. Rupture of the cyst leads to severe inflammatory reaction
      in surrounding tissues. Overall prognosis remains good with isolated reports of
      malignancy masquerading as dermoid cysts.

PMID- 16912020
TI  - A 3-month clinical trial comparing the IOP-lowering efficacy of bimatoprost and
      latanoprost in patients with normal-tension glaucoma.
AB  - This multicenter, randomized, double-blind clinical trial was undertaken to
      compare the intraocular pressure (IOP)-lowering efficacy and safety of topical
      bimatoprost 0.03% with that of latanoprost 0.005% for the treatment of patients
      with normal-tension glaucoma. After washout of all ocular hypotensive
      medications, patients with normal-tension glaucoma (n=60) were randomly assigned
      to oncedaily bimatoprost 0.03% or latanoprost 0.005% for 3 mo. Diurnal IOP
      measurements were taken at each study visit. Primary outcome measures consisted
      of mean change from baseline IOP (8 AM, Noon, 4 PM) and change in visual field.
      Secondary measures included mean IOP, ophthalmologic examination findings,
      results of clinical evaluation, and adverse events. Mean change from baseline IOP
      at each study visit was statistically significant at all diurnal measurements for
      patients taking bimatoprost and for those taking latanoprost (P<.001). The 8 AM
      mean change from baseline IOP measurement showed a significant between-group
      difference (P< or =.033) in favor of bimatoprost at both follow-up visits. After
      3 mo of treatment, mean IOP reductions from baseline ranged from 2.8 to 3.8 mm Hg
      (17.5%-21.6%) with bimatoprost and from 2.1 to 2.6 mm Hg (12.7%-16.2%) with
      latanoprost. Overall mean reduction in IOP after 3 mo of treatment was 3.4 mm Hg
      (19.9% rpar; with bimatoprost and 2.3 mm Hg (14.6%) with latanoprost (P=.035). No
      significant between-group differences were observed in incidence of adverse
      events, clinical success, or demographic variables. Bimatoprost was found to be
      more effective than latanoprost in lowering IOP in the patient with normal
      tension glaucoma. Both drugs were efficacious and well tolerated.

PMID- 16912021
TI  - Running velocities and heart rates at fixed blood lactate concentrations in young
      soccer players.
AB  - The purpose of this study was to examine the running velocities and heart rates
      at fixed lactate concentrations of young soccer players according to playing
      position and age. A total of 223 young male soccer players participated in this
      study. Each player performed incremental exercise tests on a treadmill. Running
      velocities and heart rates at 2 mmol/L-1, 2.5 mmol/L-1, 3 mmol/L-1, and 4 mmol/L
      1 blood lactate concentrations were calculated with use of the spline function.
      Data were analyzed through analysis of variance to examine differences among
      various playing positions (ie, defenders, midfielders, and forwards) and 3 age
      groups (U17, under 17 y; U19, under 19 y; and U21, under 21 y). No significant
      differences were discerned between defenders, midfielders, and forwards in terms
      of running velocities and heart rates in accordance with specified lactate
      concentrations. Running velocities corresponding to all lactate concentrations
      showed no significant differences at all age groups, but heart rates in soccer
      players in the U21 and U19 age groups were significantly lower than in the U17
      age group. Following a 3-y trial of 20 players, running velocities increased and
      heart rates decreased at all corresponding lactate concentrations. Results of
      this study suggest that (1) the endurance performance level of young soccer
      players is similar for all positions, and (2) heart rates are lowered with age
      and with training.

PMID- 16912023
TI  - Safety awareness among laboratory workers.
AB  - The purpose of this study was to assess safety awareness among laboratory
      personnel. The research group, which consisted of 84 subjects (88.4% of 95
      persons contacted), completed a questionnaire. Of the study population, 55.9%
      were male and 44.1% were female. On the subject of how to receive samples, 70.2%
      of the study group knew the correct answer. In all, 90.5% and 79.8%,
      respectively, knew what procedures should be followed after injuries or accidents
      occurred in the laboratory. The lowest number of correct responses on the
      questionnaire was associated with the topic of waste disposal. Results of this
      study show that laboratory personnel would benefit greatly from educational
      initiatives designed to promote laboratory safety.

PMID- 16912022
TI  - Effects of resistance or aerobic exercises on metabolic parameters in obese women
      who are not on a diet.
AB  - This longitudinal, controlled clinical study was conducted to compare the effects
      of resistance exercise (RE) and aerobic exercise (AE) on body mass index (BMI),
      weight, fat mass (FM), serum lipid profile, and insulin resistance in obese women
      who cannot adhere to energy-restricted diets. A total of 60 obese women with
      severe eating disorders were evaluated. Patients were randomly divided into 3
      groups: control group with no exercise (n=20), group 1 with AE (n=20), and group
      2 with RE (n=20). Demographic and anthropometric measurements were taken. Serum
      lipid fractions and fasting (FGlc) and postprandial glucose insulin (PGlc) levels
      were measured. Insulin resistance was calculated with use of homeostasis model
      assessment (HOMA-IR). Total body FM was measured by bioelectric impedance
      analysis. After 12 wk of exercise, significant decreases in BMI, waist and weight
      measurements, and FGlc, PGlc, triglyceride, and total cholesterol levels were
      noted in each of the study groups. Reduced low-density lipoprotein cholesterol
      level and FM and HOMA-IR measurements were observed only in group 1 (with AE).
      This study indicated that AE and RE training induces improvement in body fat
      composition and has a favorable metabolic effect in obese women with severe
      eating disorders.

PMID- 16912024
TI  - Assessment of the antihypertensive efficacy of various doses of delapril by
      office and ambulatory blood pressure measurement: the DEFIND study.
AB  - This study was undertaken to compare and verify the antihypertensive effects of
      various delapril doses versus placebo on office and ambulatory blood pressure
      (BP). After a 2-wk placebo period, 303 patients with mild to moderate essential
      hypertension were randomized in a double-blind study to 8 wk of treatment with
      placebo, or delapril 7.5 mg twice daily, delapril 15 mg twice daily, delapril 30
      mg twice daily, or delapril 30 mg once daily. BP changes versus baseline and
      rates of normalized office systolic blood pressure (SBP) <140 mm Hg and diastolic
      blood pressure (DBP) <90 mm Hg, as well as responder office SBP <140 mm Hg or
      reduction > or = 20 mm Hg and office DBP <90 mm Hg or reduction > or = 10 mm Hg,
      were calculated. In the intention-to-treat population (n=296), office SBP and DBP
      reductions were more notable with 30 mg twice daily (15.6/11.5 mm Hg) and 15 mg
      twice daily (14.8/12.5 mm Hg) than with other delapril regimens (30 mg once
      daily: 11.8/10.5 mm Hg; 7.5 mg twice daily: 12.9/10.1 mm Hg) and placebo (P<.05
      for DBP; P<.01 for SBP). The same was true for frequency of responders (63.8% and
      60.3%; P< or =.05 vs placebo) and normalized patients (58.6% and 53.4%; P<.05 vs
      placebo). Analysis of ambulatory BPs confirmed the accuracy of office BPs. Drug
      related adverse events occurred in 3.4% to 6.7% of patients given delapril and in
      6.5% of those given placebo. The lowest effective dose of delapril, 15 mg twice
      daily, may be recommended as the initial dose for patients who begin treatment
      with this agent.

PMID- 16912025
TI  - Bilateral synchronous primary orbital lymphoma.
AB  - Extranodal marginal zone B-cell non-Hodgkin's lymphoma affecting bilateral
      orbital regions was diagnosed in an 80-year-old man. He was given chemotherapy
      and external beam irradiation therapy. Two months after treatment, repeat orbital
      magnetic resonance imaging showed dramatically improved lesions. In this case
      report, orbital non-Hodgkin's lymphoma and treatment options are discussed.

PMID- 16912026
TI  - Effects of sevoflurane on QT dispersion and heart rate variability.
AB  - The purpose of this study was to use estimates of corrected QT dispersion (QTcd)
      and heart rate variability (HRV) to assess the effects of sevoflurane, an
      inhalation agent used frequently in clinical practice, on autonomic cardiac
      function. This study was conducted prospectively and in a blind manner on 20
      women between 38 and 51 y of age who were classified as American Society of
      Anesthesiologists stage I-II and whose treatment required total abdominal
      hysterectomy. Electrocardiograms were recorded by 12-lead Holter monitor for 5
      min before sevoflurane induction and again for 5 min at 10 min after tracheal
      intubation. Data on the first recording were considered as baseline; those on the
      second recording were viewed as final data. The study was terminated at this
      point, and surgery was allowed to proceed. QTcd and HRV values were assessed by a
      cardiologist, who was blinded to all data. All parameters were expressed as a
      mean value +/- standard deviation. Wilcoxon's test was used to compare baseline
      and final data. Statistical significance was considered as P<.05. No significant
      changes were observed between baseline and final QTcd values and between low- and
      high-frequency components (LF and HF) of HRV; nor were changes seen in the LF/HF
      ratio. With the patient under sevoflurane/ nitrous oxide anesthesia, no
      significant changes were detected in QTcd, LF, and HF values, and in the LF/HF
      ratio, whereas a significant increase (P=.001) was seen in standard deviation of
      the R-R interval, which was used as a measure of cardiac autonomic tone.

PMID- 16912027
TI  - H-Wave, a nonpharmacologic alternative for the treatment of patients with chronic
      soft tissue inflammation and neuropathic pain: a preliminary statistical outcome
      study.
AB  - The burden of chronic soft tissue inflammation and neuropathic pain on
      individuals and society is substantial. This study was conducted to evaluate the
      H-wave device--an innovative form of treatment for chronic pain and inflammation-
      in patients with persistent pain associated with injuries or conditions affecting
      the upper or lower extremities or the back. Patients with at least moderate pain
      despite conventional therapy were included in a systematic survey after they had
      been given 2 to 6 wk of treatment with the H-wave device. Measures of improvement
      involved the proportion of patients with diminished medication requirements,
      improved function, or pain relief greater than 25%. More than 60% of patients
      with pain in the lower extremities, upper extremities, or back experienced pain
      relief exceeding 25%. The proportion of patients whose function improved and who
      were able to perform a new activity was consistently greater than 50% across the
      3 anatomic subgroups. More than 40% of patients in each group were able to reduce
      or completely eliminate the use of pain medications. These benefits of treatment
      were independent of the type of pain therapy administered previously. In each
      anatomic subgroup, the proportion of patients who reported improvement on more
      than 1 of the 3 endpoints was significantly higher than the expected response to
      placebo therapy (P<.001). Results suggest that the H-wave device provided
      important benefits to patients with chronic soft tissue inflammation and
      neuropathic pain.

PMID- 16912028
TI  - Evaluation of the p53 tumor suppressor gene mutation in normal rat salivary gland
      tissue after radioiodine application: an experimental study.
AB  - In this experimental study, investigators explored p53 tumor suppressor gene
      mutation induced by low and high doses of iodine-131 sodium iodide (I-131) in
      salivary gland tissue in rats. Group 1 consisted of 10 rats; low and high I-131
      doses were applied at a 1-wk interval. First,low doses of I-131 were injected.
      (The net injected dose was 47.5-/+9.2 microCi.) After 1 wk, high doses of I-131
      were also injected. (The net injected dose was 1007.2-/+53 microCi.) Group 2
      consisted of 5 rats, and only a low I-131 dose was applied. (The net injected
      dose was 52.7-/+5.5 microCi.) The Control Group consisted of 5 rats that did not
      receive I-131. Thyroidal I-131 uptakes were calculated for Groups 1 and 2 with
      the use of a gamma camera after 24 h of injections. Immediately after uptake was
      calculated, salivary glands were resected in all groups and DNA was extracted for
      genotyping. Genomic DNA of the p53 gene exon 5 was examined by polymerase chain
      reaction single-strand conformational polymorphism. In Group 1, thyroidal I-131
      uptakes were calculated as 12.45%-/+4.14% and 9.66%-/+6.73% after low-dose and
      high-dose I-131 applications, respectively. In Group 2, thyroidal I-131 uptake
      was calculated as 13.12%-/+3.04%. In Group 1, p53 gene abnormality was seen in
      the salivary gland of only 1 of the rats. Double- and single-strand gene profiles
      showed that both alleles of this rat have a mutated single-strand conformational
      polymorphism profile of point mutation in the p53 gene exon 5. This rat received
      the highest low dose and the second highest total dose of I-131; its thyroidal
      uptakes were the second highest. In the other rats in Group 1, and in Group 2 and
      the Control Group, p53 gene abnormalities were not observed. In Groups 1 and 2, a
      significant relationship could not be discerned between thyroidal uptake of I-131
      and p53 gene mutation in the salivary gland. No significant relationship was
      observed between thyroidal uptake alterations and p53 gene mutations in salivary
      glands in Group 1. A point mutation in the p53 gene exon 5 that was seen in only
      1 of the rats in Group 1 seems related to the high-dose application of I-131,
      although coincidental occurrences could not be excluded. We believe that this
      topic is open to additional in vivo studies.

PMID- 16912029
TI  - Evaluation of vitamin K deficiency in children with acute and intractable
      diarrhea.
AB  - The purposes of this study were to determine the frequency of vitamin K
      deficiency and to assess its effects on bleeding in patients with acute and
      intractable diarrhea. A total of 90 children with diarrhea and 30 healthy
      children (group C) were included in this study. Patients were divided into 2
      groups, according to the duration of diarrhea. Complete blood count; prothrombin
      time (PT); activated prothrombin time (APTT); Factors II, VII, IX, and X; and
      protein C levels were studied in all patients. A total of 3 mg of vitamin K was
      administrated to patients with prolonged PT and/or APTT. Coagulation parameters
      were restudied 8 to 12 h after vitamin K was administered. Mean age, sex, weight,
      and breastfeeding percentage, as well as history of fever and vitamin K
      administration at birth, were similar in the 2 groups. The duration of antibiotic
      administration in group B (intractable diarrhea) was significantly longer than
      that in group A (acute diarrhea). Gastrointestinal (GI) bleeding was observed in
      3 (4.9%) infants in group A and 6 (20.7%) in group B (P<.05). The duration of
      diarrhea was significantly longer in infants with GI bleeding. Intracranial
      bleeding occurred in 1 infant with intractable diarrhea. Prolonged PT levels were
      noted in groups A and B. Significant improvement in PT and APTT and an increase
      in coagulation factors were observed after vitamin K had been administered.
      Investigators in this study conclude that coagulation parameters can be improved
      by the administration of vitamin K to children with deranged PT and APTT and
      diarrheal illness.

PMID- 16912030
TI  - Serum cytokines and bone metabolism in patients with thyroid dysfunction.
AB  - Hyperthyroidism is associated with increased bone turnover. Besides the hormones
      of calcium metabolism, locally produced factors are important in maintaining
      normal bone metabolism. Interleukin-6 (IL-6), in particular, has a major
      influence on bone turnover. In this study, serum IL-6 and tumor necrosis factor
      alpha (TNF-alpha) levels, as well as bone turnover markers and relationships
      between them, were investigated in hyperthyroidism and hypothyroidism. A total of
      20 female patients with hyperthyroidism, 15 with subclinical hyperthyroidism, 16
      with hypothyroidism, and 15 with subclinical hypothyroidism constituted the
      patient groups. In all, 15 age-matched healthy female volunteers were recruited
      as controls. When compared with controls, serum TNF-alpha levels showed no
      significant difference in any of the patient groups (P>.05). In the groups with
      hyperthyroidism and subclinical hyperthyroidism, IL-6 levels were significantly
      higher compared with control group values (P<.05). Hyperthyroid patients showed
      higher levels of alkaline phosphatase (ALP) and osteocalcin, and a higher urinary
      deoxypyridinoline/creatinine ratio, compared with controls (P<.05). In
      subclinical hyperthyroidism, only ALP was found to be higher compared with
      control values. No significant correlations were made in any group between serum
      IL-6 or TNF-alpha level and bone turnover markers. Results suggest that serum IL
      6 level and markers of bone turnover rate seem to be increased in
      hyperthyroidism. This finding may support the role of IL-6 in induction of bone
      turnover in hyperthyroid states.

PMID- 16912031
TI  - Citalopram versus fluoxetine for the treatment of patients with bulimia nervosa:
      a single-blind randomized controlled trial.
AB  - The most studied and most frequently used pharmacologic treatments in bulimia
      nervosa are the selective serotonin reuptake inhibitors (SSRIs), in particular,
      fluoxetine. Less is known about the efficacy of the other SSRIs. To compare
      fluoxetine with citalopram in the treatment of bulimic patients, 37 bulimic
      patients were randomized to receive fluoxetine (n=18) or citalopram (n=19); these
      patients were assessed with regard to clinical (ie, body mass index, pathologic
      behaviors), psychopathologic (Eating Disorder Inventory-2, Body Shape
      Questionnaire, Binge-Eating Scale, Beck Depression Inventory), personality
      (Temperament and Character Inventory), and clinical global impression measures.
      These measures were compared between the 2 treatment groups at baseline and at
      the end of treatment. Dropout rates were similar in the 2 groups. Both groups
      showed significant improvement in eating psychopathology, angry feelings, and
      clinical global impression. Patients in the fluoxetine group displayed a greater
      reduction in introjected anger, whereas those in the citalopram group displayed a
      greater reduction in depressive feelings. Both treatments showed some effect on
      outcome measures, but efficacy profiles did not overlap. Citalopram may be useful
      in depressed patients with bulimia, whereas fluoxetine is more specific for those
      with introjected anger and bulimia.

PMID- 16912032
TI  - Metabolic syndrome and its association with ischemic cerebrovascular disease.
AB  - Metabolic syndrome (MS) is the term that encompasses metabolic risk factors that
      may lead to atherosclerotic cardiovascular disease. This study was undertaken to
      investigate the prevalence of MS in patients with ischemic cerebrovascular
      disease (CVD), according to National Cholesterol Education Program/Adult
      Treatment Panel III (ATP III) criteria. A total of 40 patients who were referred
      to the emergency department and given a diagnosis of CVD were included in this
      study. Detailed medical histories, physical examination findings, heights,
      weights, and waist circumferences of patients were recorded. Fasting blood
      glucose levels and lipid profiles of patients were evaluated. Those with
      hypertension, diabetes, or hyperlipidemia were regarded as meeting at least 1 of
      the ATP III criteria. Study results were compared, especially between females and
      males. In all, 55% of patients were female, and 70% were older than 65 y. Blood
      pressure over 130/85 mm Hg was assessed in 60% of patients. Among female
      patients, 81.8% had a waist circumference greater than 88 cm; 50% of male
      patients had a waist circumference over 102 cm. A fasting blood glucose level
      above 110 mg/dL was identified in 57.5% of patients. Serum triglyceride levels in
      30% of patients were above 150 mg/L. It was noted that 33.3% of male patients had
      a high-density lipoprotein (HDL) level below 40 mg/L, and in 68.2% of female
      patients, an HDL level below 50 mg/dL was recorded. According to these findings,
      14 of 22 female patients (64%) and 13 of 18 male patients (72%) were identified
      as having MS. High rates of stroke associated with MS reveal the importance of
      forthcoming preventive approaches.

PMID- 16912033
TI  - An interesting thinner intoxication case: intrathoracic injection.
AB  - Thinners, including aromatic hydrocarbons such as toluene, xylene, and N-hexane,
      are widely used in industry for the production of plastics, varnish, paint, and
      glue. Use of these toxic agents frequently leads to chronic intoxication caused
      by abuse or misuse of solvents, which are usually taken in through inhalation.
      Thinners may have neurotoxic, myotoxic, hepatotoxic, nephrotoxic, and cardiotoxic
      systemic effects. The patient described in this report attempted to commit
      suicide by injecting 10 cc thinner into the left hemithorax. Acute chemical
      empyema developed at the left hemithorax. No bacterial growth was noted in
      empyema liquid and blood samples. Empyema was treated with tube thoracostomy, and
      full remission was observed after 33 d. No systemic toxic signs were noted, other
      than a low level of hepatotoxicity. Although pleural effusion, atelectasis, and
      pleural thickening were observed at the acute phase on computed tomography (CT)
      of the thorax, only pleural thickening persisted on CT of the thorax after 1 y.
      Investigators could not find a documented case of parenteral use of thinners in
      the medical literature.

PMID- 16912034
TI  - Differential roles of glycogen synthase kinase-3 isoforms in the regulation of
      transcriptional activation.
AB  - Glycogen synthase kinase-3 (GSK-3) exists as two structurally similar isoforms,
      alpha and beta, whose activities are negatively regulated by serine
      phosphorylation but positively controlled by tyrosine phosphorylation. We used
      GSK-3 isoform-specific small interfering RNAs, dominant negative mutants, and
      pharmacological inhibitors to search for the differential roles for both GSK-3
      isoforms in regulating transcriptional activation in cultured rat cerebral
      cortical neurons. GSK-3alpha and GSK-3beta were shown to have differentially
      regulated transactivation such that GSK-3alpha silencing/inhibition was more
      robust than GSK-3beta silencing/inhibition in causing cAMP-responsive element-
      and NF-kappaB-dependent transactivation. Moreover, protein-DNA array studies
      identified two novel GSK-3-regulated transcription factors, early growth response
      1 and Smad3/4, which were oppositely affected by GSK-3alpha or GSK-3beta
      silencing or inhibition. Taken together, our results underscore critical
      variations in the function and regulation of GSK-3alpha and GSK-3beta. The
      development of GSK-3 isoform-specific inhibitors is thus crucial for therapeutic
      intervention of GSK-3-related neuropathological conditions.

PMID- 16912035
TI  - The proprotein convertase (PC) PCSK9 is inactivated by furin and/or PC5/6A:
      functional consequences of natural mutations and post-translational
      modifications.
AB  - PCSK9 is the ninth member of the proprotein convertase (PC) family. Some of its
      natural mutations have been genetically associated with the development of a
      dominant form of familial hyper- or hypocholesterolemia. The exact mechanism of
      action of PCSK9 is not clear, although it is known to enhance the intracellular
      degradation of the low density lipoprotein (LDL) receptor in acidic compartments,
      likely the endosomes/lysosomes. We analyzed the post-translational modifications
      of PCSK9 and show that it is sulfated within its prosegment at Tyr38. We also
      examined the susceptibility of PCSK9 to proteolytic cleavage by the other members
      of the PC family. The data show that the natural gain-of-function mutations
      R218S, F216L, and D374Y associated with hypercholesterolemia result in total or
      partial loss of furin/PC5/6A processing at the motif RFHR218 downward arrow. In
      contrast, the loss-of-function mutations A443T and C679X lead either to the lack
      of trans-Golgi network/recycling endosome localization and an enhanced
      susceptibility to furin cleavage (A443T) or to the inability of PCSK9 to exit the
      endoplasmic reticulum (C679X). Furthermore, we report the presence of both native
      and furin-like cleaved forms of PCSK9 in circulating human plasma. Thus, we
      propose that PCSK9 levels are finely regulated by the basic amino acid
      convertases furin and PC5/6A. The latter may reduce the lifetime of this
      proteinase and its ability to degrade the cell-surface LDL receptor, thereby
      regulating the levels of circulating LDL cholesterol.

PMID- 16912036
TI  - Src family kinases phosphorylate the Bcr-Abl SH3-SH2 region and modulate Bcr-Abl
      transforming activity.
AB  - Bcr-Abl is the oncogenic protein-tyrosine kinase responsible for chronic
      myelogenous leukemia. Recently, we observed that inhibition of myeloid Src family
      kinase activity (e.g. Hck, Lyn, and Fyn) induces growth arrest and apoptosis in
      Bcr-Abl-transformed cells, suggesting that cell transformation by Bcr-Abl
      involves Src family kinases (Wilson, M. B., Schreiner, S. J., Choi, H. J.,
      Kamens, J., and Smithgall, T. E. (2002) Oncogene 21, 8075-8088). Here, we report
      the unexpected observation that Hck, Lyn, and Fyn strongly phosphorylate the SH3
      SH2 region of Bcr-Abl. Seven phosphorylation sites were identified by matrix
      assisted laser desorption ionization time-of-flight mass spectrometry: Tyr89 and
      Tyr134 in the Abl-derived SH3 domain; Tyr147 in the SH3-SH2 connector; and
      Tyr158, Tyr191, Tyr204, and Tyr234 in the SH2 domain. SH3 domain Tyr89, the most
      prominent phosphorylation site in vitro, was strongly phosphorylated in chronic
      myelogenous leukemia cells in a Src family kinase-dependent manner. Substitution
      of the SH3-SH2 tyrosine phosphorylation sites with phenylalanine substantially
      reduced Bcr-Abl-mediated transformation of TF-1 myeloid cells to cytokine
      independence. The positions of these tyrosines in the crystal structure of the c
      Abl core and the transformation defect of the corresponding Bcr-Abl mutants
      together suggest that phosphorylation of the SH3-SH2 region by Src family kinases
      impacts Bcr-Abl protein conformation and signaling.

PMID- 16912037
TI  - A model for the proteolipid ring and bafilomycin/concanamycin-binding site in the
      vacuolar ATPase of Neurospora crassa.
AB  - The vacuolar ATPase has been implicated in a variety of physiological processes
      in eukaryotic cells. Bafilomycin and concanamycin, highly potent and specific
      inhibitors of the vacuolar ATPase, have been widely used to investigate the
      enzyme. Derivatives have been developed as possible therapeutic drugs. We have
      used random mutagenesis and site-directed mutagenesis to identify 23 residues in
      the c subunit involved in binding these drugs. We generated a model for the
      structure of the ring of c subunits in Neurospora crassa by using data from the
      crystal structure of the homologous subunits of the bacterium Enterococcus hirae
      (Murata, T., Yamato, I., Kakinuma, Y., Leslie, A. G., and Walker, J. E. (2005)
      Science 308, 654-659). In the model 10 of the 11 mutation sites that confer the
      highest degree of resistance are closely clustered. They form a putative drug
      binding pocket at the interface between helices 1 and 2 on one c subunit and
      helix 4 of the adjacent c subunit. The excellent fit of the N. crassa sequence to
      the E. hirae structure and the degree to which the structural model predicts the
      clustering of these residues suggest that the folding of the bacterial and
      eukaryotic polypeptides is very similar.

PMID- 16912038
TI  - Conversion of a putative Agrobacterium sugar-binding protein into a FRET sensor
      with high selectivity for sucrose.
AB  - Glucose is the main sugar transport form in animals, whereas plants use sucrose
      to supply non-photosynthetic organs with carbon skeletons and energy. Many
      aspects of sucrose transport, metabolism, and signaling are not well understood,
      including the route of sucrose efflux from leaf mesophyll cells and transport
      across vacuolar membranes. Tools that can detect sucrose with high spatial and
      temporal resolution in intact organs may help elucidate the players involved.
      Here, FRET sensors were generated by fusing putative sucrose-binding proteins to
      green fluorescent protein variants. Plant-associated bacteria such as Rhizobium
      and Agrobacterium can use sucrose as a nutrient source; sugar-binding proteins
      were, thus, used as scaffolds for developing sucrose nanosensors. Among a set of
      putative sucrose-binding protein genes cloned in between eCFP and eYFP and tested
      for sugar-dependent FRET changes, an Agrobacterium sugar-binding protein bound
      sucrose with 4 mum affinity. This FLIPsuc-4mu protein also recognized other
      sugars including maltose, trehalose, and turanose and, with lower efficiency,
      glucose and palatinose. Homology modeling enabled the prediction of binding
      pocket mutations to modulate the relative affinity of FLIPsuc-4mu for sucrose,
      maltose, and glucose. Mutant nanosensors showed up to 50- and 11-fold increases
      in specificity for sucrose over maltose and glucose, respectively, and the
      sucrose binding affinity was simultaneously decreased to allow detection in the
      physiological range. In addition, the signal-to-noise ratio of the sucrose
      nanosensor was improved by linker engineering. This novel reagent complements
      FLIPs for glucose, maltose, ribose, glutamate, and phosphate and will be used for
      analysis of sucrose-derived carbon flux in bacterial, fungal, plant, and animal
      cells.

PMID- 16912039
TI  - Identification of common and unique peptide substrate preferences for the UDP
      GalNAc:polypeptide alpha-N-acetylgalactosaminyltransferases T1 and T2 derived
      from oriented random peptide substrates.
AB  - A large family of UDP-GalNAc:polypeptide alpha-N-acetylgalactosaminyltransferases
      (ppGalNAc Ts) catalyzes the first step of mucin-type protein O-glycosylation by
      transferring GalNAc to serine and threonine residues of acceptor polypeptides.
      The acceptor peptide substrate specificity and specific protein targets of the
      individual ppGalNAc T family members remain poorly characterized and poorly
      understood, despite the fact that mutations in two individual isoforms are
      deleterious to man and the fly. In this work a series of oriented random peptide
      substrate libraries, based on the GAGAXXXTXXXAGAGK sequence motif (where X =
      randomized positions), have been used to obtain the first comprehensive
      determination of the peptide substrate specificities of the mammalian ppGalNAc T1
      and T2 isoforms. ppGalNAc T-glycosylated random peptides were isolated by lectin
      affinity chromatography, and transferase amino acid preferences were determined
      by Edman amino acid sequencing. The results reveal common and unique position
      sensitive features for both transferases, consistent with previous reports of the
      preferences of ppGalNAc T1 and T2. The random peptide substrates also reveal
      additional specific features that have never been described before that are
      consistent with the x-ray crystal structures of the two transferases and
      furthermore are reflected in a data base analysis of in vivo O-glycosylation
      sites. By using the transferase-specific preferences, optimum and selective
      acceptor peptide substrates have been generated for each transferase. This
      approach represents a relatively complete, facile, and reproducible method for
      obtaining ppGalNAc T peptide substrate specificity. Such information will be
      invaluable for identifying isoform-specific peptide acceptors, creating isoform
      specific substrates, and predicting O-glycosylation sites.

PMID- 16912040
TI  - Arrestin is required for agonist-induced trafficking of voltage-dependent calcium
      channels.
AB  - Many metabotropic receptors in the nervous system act through signaling pathways
      that result in the inhibition of voltage-dependent calcium channels. Our previous
      findings showed that activation of seven-transmembrane receptors results in the
      internalization of calcium channels. This internalization takes place within a
      few seconds, raising the question of whether the endocytic machinery is in close
      proximity to the calcium channel to cause such rapid internalization. Here we
      show that voltage-dependent calcium channels are pre-associated with arrestin, a
      protein known to play a role in receptor trafficking. Upon GABAB receptor
      activation, receptors are recruited to the arrestin-channel complex and
      internalized. beta-Arrestin 1 selectively binds to the SNARE-binding region of
      the calcium channel. Peptides containing the arrestin-binding site of the channel
      disrupt agonist-induced channel internalization. Taken together these data
      suggest a novel neuronal role for arrestin.

PMID- 16912041
TI  - Contribution of interferon-beta to the murine macrophage response to the toll
      like receptor 4 agonist, lipopolysaccharide.
AB  - Interferon-beta (IFN-beta) has been identified as the signature cytokine induced
      via the Toll-like receptor (TLR) 4, "MyD88-independent" signaling pathway in
      macrophages stimulated by Gram-negative bacterial lipopolysaccharide (LPS). In
      this study, we analyzed the responses of macrophages derived from wild-type (IFN
      beta(+/+)) mice or mice with a targeted mutation in IFN-beta (IFN-beta(-/-)) to
      the prototype TLR4 agonist, Escherichia coli LPS. A comparison of basal and LPS
      induced gene expression (by reverse transcription-PCR, real-time PCR, and
      Affymetrix microarray analyses) resulted in the identification of four distinct
      patterns of gene expression affected by IFN-beta deficiency. Analysis of a subset
      of each group of differentially regulated genes by computer-assisted promoter
      analysis revealed putative IFN-responsive elements in all genes examined. LPS
      induced activation of intracellular signaling molecules, STAT1 Tyr-701, STAT1 Ser
      727, and Akt, but not p38, JNK, and ERK MAPK proteins, was significantly
      diminished in IFN-beta(-/-) versus IFN-beta(+/+) macrophages. "Priming" of IFN
      beta(-/-) macrophages with exogenous recombinant IFN-beta significantly increased
      levels of LPS-induced gene expression for induction of monocyte chemotactic
      protein 5, inducible nitric-oxide synthase, IP-10, and IL-12 p40 mRNA, whereas no
      increase or relatively small increases were observed for IL-1beta, IL-6, monocyte
      chemotactic protein 1, and MyD88 mRNA. Finally, IFN-beta(-/-) mice challenged in
      vivo with LPS exhibited increased survival when compared with wild-type IFN
      beta(+/+) controls, indicating that IFN-beta contributes to LPS-induced
      lethality; however, not to the extent that one observes in mice with more
      complete pathway deficiencies (e.g. TLR4(-/-) or TRIF(-/-) mice). Collectively,
      these findings reveal unanticipated regulatory roles for IFN-beta in response to
      LPS in vitro and in vivo.

PMID- 16912042
TI  - p21WAF1/Cip1 suppresses keratinocyte differentiation independently of the cell
      cycle through transcriptional up-regulation of the IGF-I gene.
AB  - p21 plays a dual role in keratinocyte growth and differentiation control. It
      restricts the number of keratinocyte stem cell populations while inhibiting the
      later stages of differentiation independently of the cell cycle. The
      molecular/biochemical mechanism for the differentiation suppressive function of
      p21 is unknown. Here we show that elevated p21 expression leads to activation of
      MAPK family members in a keratinocyte-specific and cell cycle-independent manner,
      and up-regulation of MAPK activity can explain the inhibitory effects of p21 on
      differentiation. p21 induces transcription of several genes with MAPK activation
      potential. Although several of these genes are induced by p21 in a MAPK-dependent
      manner, expression of IGF-I is induced upstream of MAPK activation. IGF-I
      stimulation is by itself sufficient to cause MAPK activation and inhibit
      differentiation and suppression of IGF-I signaling by knock down of the cognate
      receptor (IGF-R1), diminishing the ability of p21 to activate MAPK and suppress
      differentiation. Thus, in keratinocytes, the ability of p21 to suppress
      differentiation can be explained by cell type-specific activation of the MAPK
      cascade by transcriptional up-regulation of the IGF-I gene.

PMID- 16912043
TI  - Structure of the thiazole biosynthetic enzyme THI1 from Arabidopsis thaliana.
AB  - Thiamin pyrophosphate is an essential coenzyme in all organisms that depend on
      fermentation, respiration or photosynthesis to produce ATP. It is synthesized
      through two independent biosynthetic routes: one for the synthesis of 2-methyl-4
      amino-5-hydroxymethylpyrimidine pyrophosphate (pyrimidine moiety) and another for
      the synthesis of 4-methyl-5-(beta-hydroxyethyl) thiazole phosphate (thiazole
      moiety). Herein, we will describe the three-dimensional structure of THI1 protein
      from Arabidopsis thaliana determined by single wavelength anomalous diffraction
      to 1.6A resolution. The protein was produced using heterologous expression in
      bacteria, unexpectedly bound to 2-carboxylate-4-methyl-5-beta-(ethyl adenosine 5
      diphosphate) thiazole, a potential intermediate of the thiazole biosynthesis in
      Eukaryotes. THI1 has a topology similar to dinucleotide binding domains and
      although details concerning its function are unknown, this work provides new
      clues about the thiazole biosynthesis in Eukaryotes.

PMID- 16912044
TI  - Negative modulation of RXRalpha transcriptional activity by small ubiquitin
      related modifier (SUMO) modification and its reversal by SUMO-specific protease
      SUSP1.
AB  - Retinoid X receptor alpha (RXRalpha) belongs to a family of ligand-activated
      transcription factors that regulate many aspects of metazoan life. Here we
      demonstrate that RXRalpha is a target substrate of a small ubiquitin-related
      modifier (SUMO)-specific protease, SUSP1, which is capable of controlling the
      transcriptional activity of RXRalpha. RXRalpha was modified by SUMO-1 in vivo as
      well as in vitro, and the Lys-108 residue within the IKPP sequence of RXRalpha AF
      1 domain was identified as the major SUMO-1 acceptor site. Prevention of SUMO
      modification by Lys-to-Arg mutation led to an increase not only in the
      transcriptional activity of RXRalpha but also in the activity of its
      heterodimeric complex with retinoic acid receptor-alpha or peroxisome
      proliferator-activated receptor-gamma (PPARgamma). SUSP1 co-localized with
      RXRalpha in the nucleus and removed SUMO-1 from RXRalpha but not from androgen
      receptor or PPARgamma. Moreover, overexpression of SUSP1 caused an increase in
      the transcriptional activity of RXRalpha, whereas small hairpin RNA-mediated
      knockdown of endogenous SUSP1 led to a decrease in RXRalpha activity. These
      results suggest that SUSP1 plays an important role in the control of the
      transcriptional activity of RXRalpha and thus in the RXRalpha-mediated cellular
      processes.

PMID- 16912045
TI  - The Chk1-mediated S-phase checkpoint targets initiation factor Cdc45 via a
      Cdc25A/Cdk2-independent mechanism.
AB  - DNA damage induced by the carcinogen benzo[a]pyrene dihydrodiol epoxide (BPDE)
      induces a Chk1-dependent S-phase checkpoint. Here, we have investigated the
      molecular basis of BPDE-induced S-phase arrest. Chk1-dependent inhibition of DNA
      synthesis in BPDE-treated cells occurred without detectable changes in Cdc25A
      levels, Cdk2 activity, or Cdc7/Dbf4 interaction. Overexpression studies showed
      that Cdc25A, cyclin A/Cdk2, and Cdc7/Dbf4 were not rate-limiting for DNA
      synthesis when the BPDE-induced S-phase checkpoint was active. To investigate
      other potential targets of the S-phase checkpoint, we tested the effects of BPDE
      on the chromatin association of DNA replication factors. The levels of chromatin
      associated Cdc45 (but not soluble Cdc45) were reduced concomitantly with BPDE
      induced Chk1 activation and inhibition of DNA synthesis. The chromatin
      association of Mcm7, Mcm10, and proliferating cell nuclear antigen was unaffected
      by BPDE treatment. However, the association between Mcm7 and Cdc45 in the
      chromatin fraction was inhibited in BPDE-treated cells. Chromatin
      immunoprecipitation analyses demonstrated reduced association of Cdc45 with the
      beta-globin origin of replication in BPDE-treated cells. The inhibitory effects
      of BPDE on DNA synthesis, Cdc45/Mcm7 associations, and interactions between Cdc45
      and the beta-globin locus were abrogated by the Chk1 inhibitor UCN-01. Taken
      together, our results show that the association between Cdc45 and Mcm7 at origins
      of replication is negatively regulated by Chk1 in a Cdk2-independent manner.
      Therefore, Cdc45 is likely to be an important target of the Chk1-mediated S-phase
      checkpoint.

PMID- 16912046
TI  - Characterization of 3'hExo, a 3' exonuclease specifically interacting with the 3'
      end of histone mRNA.
AB  - The 3' end of mammalian histone mRNAs consisting of a conserved stem-loop and a
      terminal ACCCA interacts with a recently identified human 3' exonuclease
      designated 3'hExo. The sequence-specific interaction suggests that 3'hExo may
      participate in the degradation of histone mRNAs. ERI-1, a Caenorhabditis elegans
      homologue of 3'hExo, has been implicated in degradation of small interfering
      RNAs. We introduced a number of mutations to 3'hExo to identify residues required
      for RNA binding and catalysis. To assure that the introduced mutations
      specifically target one of these two activities of 3'hExo rather than cause
      global structural defects, the mutant proteins were tested in parallel for the
      ability both to bind the stem-loop RNA and to degrade RNA substrates. Our
      analysis confirms that 3'hExo is a member of the DEDDh family of 3' exonucleases.
      Specific binding to the RNA requires the SAP domain and two lysines located
      immediately to its C terminus. 3'hExo binds with the highest affinity to the wild
      type 3' end of histone mRNA, and any changes to this sequence reduce efficiency
      of binding. 3'hExo has only residual, if any, 3' exonuclease activity on DNA
      substrates and localizes mostly to the cytoplasm, suggesting that in vivo it
      performs exclusively RNA-specific functions. Efficient degradation of RNA
      substrates by 3'hExo requires 2' and 3' hydroxyl groups at the last nucleotide.
      3'hExo removes 3' overhangs of small interfering RNAs, whereas the double
      stranded region is resistant to the enzymatic activity.

PMID- 16912047
TI  - E2F1 modulates p38 MAPK phosphorylation via transcriptional regulation of ASK1
      and Wip1.
AB  - The E2F family of transcription factors regulates a diverse array of cellular
      functions, including cell proliferation, cell differentiation, and apoptosis.
      Recent studies indicate that E2F can also regulate transcription of upstream
      components of signal transduction pathways. We show here that E2F1 modulates the
      activity of the p38 MAPK pathway via E2F1-induced transient up-regulation of p38
      MAPK phosphorylation. The mechanism by which E2F1 modulates p38 MAPK
      phosphorylation involves transcriptional induction of the kinase ASK1, a member
      of the MAPKKK family that phosphorylates p38 MKKs. Subsequent E2F-dependent down
      regulation of the p38 signaling pathway is achieved through E2F-induced up
      regulation of Wip1, a phosphatase that dephosphorylates and inactivates p38. Both
      ASK1 and Wip1 are essential mediators of the E2F-p38 connection: knock down of
      ASK1 inhibits E2F1-induced phosphorylation of p38, whereas knock down of Wip1
      prolongs E2F1-induced p38 phosphorylation. Furthermore, Wip1 knock down enhances
      E2F1-induced apoptosis. Therefore, our data reveal a novel link between a central
      signaling pathway and the transcription factor E2F and identify Wip1 as a
      modulator of E2F1-induced apoptosis.

PMID- 16912048
TI  - The deg proteases protect Synechocystis sp. PCC 6803 during heat and light
      stresses but are not essential for removal of damaged D1 protein during the
      photosystem two repair cycle.
AB  - Members of the DegP/HtrA (or Deg) family of proteases are found widely in nature
      and play an important role in the proteolysis of misfolded and damaged proteins.
      As yet, their physiological role in oxygenic photosynthetic organisms is unclear,
      although it has been widely speculated that they participate in the degradation
      of the photodamaged D1 subunit in the photosystem two complex (PSII) repair
      cycle, which is needed to maintain PSII activity in both cyanobacteria and
      chloroplasts. We have examined the role of the three Deg proteases found in the
      cyanobacterium Synechocystis sp. PCC 6803 through analysis of double and triple
      insertion mutants. We have discovered that these proteases show overlap in
      function and are involved in a number of key physiological responses ranging from
      protection against light and heat stresses to phototaxis. In previous work, we
      concluded that the Deg proteases played either a direct or an indirect role in
      PSII repair in a glucose-tolerant version of Synechocystis 6803 (Silva, P., Choi,
      Y. J., Hassan, H. A., and Nixon, P. J. (2002) Philos. Trans. R. Soc. Lond. B
      Biol. Sci. 357, 1461-1467). In this work, we have now been able to demonstrate
      unambiguously, using a triple deg mutant created in the wild type strain of
      Synechocystis 6803, that the Deg proteases are not obligatory for PSII repair and
      D1 degradation. We therefore conclude that although the Deg proteases are needed
      for photoprotection of Synechocystis sp. PCC 6803, they do not play an essential
      role in D1 turnover and PSII repair in vivo.

PMID- 16912049
TI  - A pyruvate cycling pathway involving cytosolic NADP-dependent isocitrate
      dehydrogenase regulates glucose-stimulated insulin secretion.
AB  - Glucose-stimulated insulin secretion (GSIS) from pancreatic islet beta-cells is
      central to control of mammalian fuel homeostasis. Glucose metabolism mediates
      GSIS in part via ATP-regulated K+ (KATP) channels, but multiple lines of evidence
      suggest participation of other signals. Here we investigated the role of
      cytosolic NADP-dependent isocitrate dehydrogenase (ICDc) in control of GSIS in
      beta-cells. Delivery of small interfering RNAs specific for ICDc caused
      impairment of GSIS in two independent robustly glucose-responsive rat insulinoma
      (INS-1-derived) cell lines and in primary rat islets. Suppression of ICDc also
      attenuated the glucose-induced increments in pyruvate cycling activity and in
      NADPH levels, a predicted by-product of pyruvate cycling pathways, as well as the
      total cellular NADP(H) content. Metabolic profiling of eight organic acids in
      cell extracts revealed that suppression of ICDc caused increases in lactate
      production in both INS-1-derived cell lines and primary islets, consistent with
      the attenuation of pyruvate cycling, with no significant changes in other
      intermediates. Based on these studies, we propose that a pyruvate cycling pathway
      involving ICDc plays an important role in control of GSIS.

PMID- 16912050
TI  - Regulation of steady-state beta-amyloid levels in the brain by neprilysin and
      endothelin-converting enzyme but not angiotensin-converting enzyme.
AB  - The deposition of beta-amyloid in the brain is a pathological hallmark of
      Alzheimer disease (AD). Normally, the accumulation of beta-amyloid is prevented
      in part by the activities of several degradative enzymes, including the
      endothelin-converting enzymes, neprilysin, insulin-degrading enzyme, and plasmin.
      Recent reports indicate that another metalloprotease, angiotensin-converting
      enzyme (ACE), can degrade beta-amyloid in vitro and in cellular overexpression
      experiments. In addition, ACE gene variants are linked to AD risk in several
      populations. Angiotensin-converting enzyme, neprilysin and endothelin-converting
      enzyme function as vasopeptidases and are the targets of drugs designed to treat
      cardiovascular disorders, and ACE inhibitors are commonly prescribed. We
      investigated the potential physiological role of ACE in regulating endogenous
      brain beta-amyloid levels for two reasons: first, to determine whether beta
      amyloid degradation might be the mechanism by which ACE is associated with AD,
      and second, to determine whether ACE inhibitor drugs might block beta-amyloid
      degradation in the brain and potentially increase the risk for AD. We analyzed
      beta-amyloid accumulation in brains from ACE-deficient mice and in mice treated
      with ACE inhibitors and found that ACE deficiency did not alter steady-state beta
      amyloid concentration. In contrast, beta-amyloid levels are significantly
      elevated in endothelin-converting enzyme and neprilysin knock-out mice, and
      inhibitors of these enzymes cause a rapid increase in beta-amyloid concentration
      in the brain. The results of these studies do not support a physiological role
      for ACE in the degradation of beta-amyloid in the brain but confirm roles for
      endothelin-converting enzyme and neprilysin and indicate that reductions in these
      enzymes result in additive increases in brain amyloid beta-peptide levels.

PMID- 16912051
TI  - Distinct structural elements in the first membrane-spanning segment of the
      epithelial sodium channel.
AB  - Epithelial Na+ channels (ENaCs) comprise three subunits that have been proposed
      to be arranged in either an alpha2betagamma or a higher ordered configuration.
      Each subunit has two putative membrane-spanning segments (M1 and M2),
      intracellular amino and carboxyl termini, and a large extracellular loop. We have
      used the TOXCAT assay (a reporter assay for transmembrane segment
      homodimerization) to identify residues within the transmembrane segments of ENaC
      that may participate in important structural interactions within ENaC, with which
      we identified a candidate site within alphaM1. We performed site-directed
      mutagenesis at this site and found that, although the mutants reduced channel
      activity, ENaC protein expression at the plasma membrane was unaffected. To
      deduce the role of alphaM1 in the pore structure of ENaC, we performed tryptophan
      scanning mutagenesis throughout alphaM1 (residues 110-130). We found that
      mutations within the amino-terminal part of alphaM1 had effects on activity and
      selectivity with a periodicity consistent with a helical structure but no effect
      on channel surface expression. We also observed that mutations within the
      carboxyl-terminal part of alphaM1 had effects on activity and selectivity but
      with no apparent periodicity. Additionally, these mutants reduced channel surface
      expression. Our data support a model in which the amino-terminal half of alphaM1
      is alpha-helical and packs against structural element(s) that contribute to the
      ENaC pore. Furthermore, these data suggest that the carboxyl-terminal half of
      alphaM1 may be helical or assume a different conformation and may be involved in
      tertiary interactions essential to proper channel folding or assembly. Together,
      our data suggest that alphaM1 is divided into two distinct regions.

PMID- 16912052
TI  - Being specific about race-specific medicine.
AB  - Gary Puckrein's paper "BiDil: From Another Vantage Point" misrepresents rather
      than refutes our previously published analysis of BiDil. Puckrein claims that if
      our analysis were to prevail, patients would be denied life-saving therapy. Any
      reasonable reading of our paper suggests exactly the opposite. Indeed, based on
      the evidence, we urge doctors to prescribe the generics or BiDil itself as they
      see fit, but without regard to the race of their patient.

PMID- 16912053
TI  - BiDil: from another vantage point.
AB  - In a recent Health Affairs Web Exclusive, Pamela Sankar and Jonathan Kahn argue
      against the Food and Drug Administration's approval of BiDil as a new drug for
      the treatment of heart failure in African Americans. Their paper questions the
      existence of disparities between African American and other heart-failure
      patients and the motivations of BiDil's developers and manufacturer. The
      disparities are confirmed and persistent, however, and BiDil's effectiveness is
      proven. If the authors' logic were to prevail, patients would be denied life
      saving therapy. Continued investigation will likely narrow identification of
      patients who will benefit.

PMID- 16912055
TI  - Circulating CD34+ cells, metabolic syndrome, and cardiovascular risk.
AB  - AIMS: Circulating progenitor cells are believed to participate in cardiovascular
      (CV) homeostasis and their exhaustion has been linked to CV damage. As general
      agreement on their characterization is lacking, this work was carried out to
      assess the relationships between different antigenic profiles of progenitor cells
      and CV risk, with special regard to metabolic syndrome (MetSyn). METHODS AND
      RESULTS: CD34, CD133, and KDR were used to quantify circulating progenitors in
      214 subjects at different levels of CV risk. In a cross-analysis of six different
      cell subtypes (CD34(+), CD133(+), CD34(+)CD133(+), CD34(+)KDR(+), CD133(+)KDR(+),
      and CD34(+)CD133(+)KDR(+)), CD34(+) progenitors showed the best correlation with
      CV parameters and risk estimates. Components of the MetSyn were all characterized
      by reduction of CD34(+) cells and acted synergistically in decreasing CD34(+)
      cell count. Moreover, CD34(+) cell count demonstrated a high performance in
      detecting high CV risk. CONCLUSION: These data demonstrate that CD34 identifies
      progenitor cells linked to CV risk, showing a close negative correlation between
      CD34(+) cells and CV risk, as well as a synergic detrimental effect of clustered
      metabolic components. Progenitor cell count may be used as a surrogate marker of
      CV risk, whereas extensive antigenic characterization may not be useful for this
      purpose.

PMID- 16912056
TI  - Preptin, another peptide product of the pancreatic beta-cell, is osteogenic in
      vitro and in vivo.
AB  - Several hormones that regulate nutritional status also impact on bone metabolism.
      Preptin is a recently isolated 34-amino acid peptide hormone that is cosecreted
      with insulin and amylin from the pancreatic beta-cells. Preptin corresponds to
      Asp(69)-Leu(102) of pro-IGF-II. Increased circulating levels of a pro-IGF-II
      peptide complexed with IGF-binding protein-2 have been implicated in the high
      bone mass phenotype observed in patients with chronic hepatitis C infection. We
      have assessed preptin's activities on bone. Preptin dose-dependently stimulated
      the proliferation (cell number and DNA synthesis) of primary fetal rat
      osteoblasts and osteoblast-like cell lines at periphysiological concentrations
      (>10(-11) M). In addition, thymidine incorporation was stimulated in murine
      neonatal calvarial organ culture, likely reflecting the proliferation of cells
      from the osteoblast lineage. Preptin did not affect bone resorption in this
      model. Preptin induced phosphorylation of p42/p44 MAP kinases in osteoblastic
      cells in a dose-dependent manner (10(-8)-10(-10) M), and its proliferative
      effects on primary osteoblasts were blocked by MAP kinase kinase inhibitors.
      Preptin also reduced osteoblast apoptosis induced by serum deprivation, reducing
      the number of apoptotic cells by >20%. In vivo administration of preptin
      increased bone area and mineralizing surface in adult mice. These data
      demonstrate that preptin, which is cosecreted from the pancreatic beta-cell with
      amylin and insulin, is anabolic to bone and may contribute to the preservation of
      bone mass observed in hyperinsulinemic states such as obesity.

PMID- 16912057
TI  - Increased IRS-2 content and activation of IGF-I pathway contribute to enhance
      beta-cell mass in fetuses from undernourished pregnant rats.
AB  - We have previously shown that fetuses from undernourished (U) pregnant rats
      exhibited an increased beta-cell mass probably related to an enhanced IGF-I
      replicative response. Because IGF-I signaling pathways have been implicated in
      regulating beta-cell growth, we investigated in this study the IGF-I transduction
      system in U fetuses. To this end, an in vitro model of primary fetal islets was
      developed to characterize glucose/IGF-I-mediated signaling that specially
      influences beta-cell proliferation. We found that U fetal islets showed a greater
      replicative response to glucose and IGF-I than controls. Furthermore, insulin
      receptor substrate (IRS)-2 protein and its association with p85 were also
      increased. In the complete absence of IGF-I or stimulatory glucose, U islets
      presented an increased basal phosphorylation of downstream signals of the
      phosphatidylinositol 3-kinase (PI3K) pathway such as PKB, glycogen synthase
      kinase (GSK)3alpha/beta, PKCzeta, and mammalian target of rapamycin (mTOR).
      Similarly, phosphorylation of these proteins (except GSK3alpha/beta) by glucose
      and IGF-I was augmented even though total protein content remained unchanged.
      Downstream of PKB, direct glucose activation of mTOR was increased as well. In
      contrast, ERK1/2 phosphorylation was unaffected by undernutrition, but ERK
      activation seemed to be required to induce a higher proliferative response in U
      islets. In conclusion, we have demonstrated that fetal U islets show increased
      IRS-2 content and an enhancement in both basal and glucose/IGF-I activations of
      the IRS-2/PI3K/PKB pathway. These molecular changes may be responsible for the
      greater glucose/IGF-I islet replication and contribute to the increased beta-cell
      mass found in these fetuses.

PMID- 16912058
TI  - Energy expenditure adjusted for body composition differentiates constitutional
      thinness from both normal subjects and anorexia nervosa.
AB  - Constitutional thinness (CT) is characterized by a low and stable body mass index
      (BMI) without any hormonal abnormality. To understand the weight steadiness,
      energetic metabolism was evaluated. Seven CT, seven controls, and six anorexia
      nervosa (AN) young women were compared. CT and AN had a BMI <16.5 kg/m(2). Four
      criteria were evaluated: 1) energy balance including diet record, resting
      metabolic rate (RMR) (indirect calorimetry), total energy expenditure (TEE)
      (doubly labeled water), physical activity; 2) body composition (dual-energy X-ray
      absorptiometry); 3) biological markers (leptin, IGF-I, free T3); 4) psychological
      profile of eating behavior. The normality of free T3 (3.7 +/- 0.5 pmol/l), IGF-I
      (225 +/- 93 ng/ml), and leptin (8.3 +/- 3.4 ng/ml) confirmed the absence of
      undernutrition in CT. Their psychological profiles revealed a weight gain desire.
      TEE (kJ/day) in CT (8,382 +/- 988) was not found significantly different from
      that of controls (8,793 +/- 845) and AN (8,001 +/- 2,152). CT food intake (7,565
      +/- 908 kJ/day) was found similar to that of controls (7,961 +/- 1,452 kJ/day)
      and higher than in AN (4,894 +/- 703 kJ/day), thus explaining the energy
      metabolism balance. Fat-free mass (FFM) (kg) was similar in CT and AN (32.5 +/-
      2.9 vs. 34.1 +/- 1.9) and higher in controls (37.8 +/- 1.6). While RMR absolute
      values (kJ/day) were lower in CT (4,839 +/- 473) than in controls (5,576 +/-
      209), RMR values adjusted for FFM were the highest in CT. TEE-to-FFM ratio was
      also higher in CT than in controls. Energetic metabolism balance maintains a
      stable low weight in CT. An increased energy expenditure-to-FFM ratio
      differentiates CT from controls and could account for the resistance to weight
      gain observed in CT.

PMID- 16912059
TI  - Pancreatic islet function in omega-3 fatty acid-depleted rats: alteration of
      calcium fluxes and calcium-dependent insulin release.
AB  - Considering the insufficient supply of long-chain polyunsaturated omega-3 fatty
      acids often prevailing in Western populations, this report deals mainly with
      alterations of Ca(2+) fluxes and Ca(2+)-dependent insulin secretory events in
      isolated pancreatic islets from omega-3-depleted rats. In terms of (45)Ca(2+)
      handling, the islets from omega-3-depleted rats, compared with those from normal
      animals, displayed an unaltered responsiveness to an increase in extracellular
      K(+) concentration, a lower inflow rate and lower fractional outflow rate of the
      divalent cation, and higher (45)Ca(2+)-labeled cellular pool(s) at isotopic
      equilibrium. The latter anomaly was corrected 120 min after intravenous injection
      of a novel medium-chain triglyceride-fish oil (MCT:FO) emulsion, distinct from a
      control omega-3-poor MCT-olive oil (MCT:OO) emulsion. At 8.3 mM D-glucose,
      insulin release was higher in islets from omega-3-depleted rats vs. control
      animals, coinciding with a higher cytosolic Ca(2+) concentration. The relative
      magnitude of the increase in insulin output attributable to a rise in D-glucose
      as well as extracellular Ca(2+) or K(+) concentration, to the absence vs.
      presence of verapamil and to the presence vs. absence of extracellular Ca(2+),
      theophylline, phorbol 12-myristate 13-acetate, or Ba(2+), was always more
      pronounced in islets from omega-3-depleted rats injected with the MCT:OO compared
      with the MCT:FO emulsion. A comparable situation prevailed when comparing islets
      from noninjected omega-3-depleted and normal rats. In light of these and previous
      findings, we propose that an impairment of Na(+),K(+)-ATPase activity plays a
      major, although not an exclusive, role in the perturbation of Ca(2+) fluxes and
      Ca(2+)-dependent secretory events in the islets from omega-3-depleted rats.

PMID- 16912060
TI  - Growth hormone-releasing hormone and corticotropin-releasing hormone enhance non
      rapid-eye-movement sleep after sleep deprivation.
AB  - The neuropeptides growth hormone (GH)-releasing hormone (GHRH) and corticotropin
      releasing hormone (CRH) regulate sleep and nocturnal hormone secretion in a
      reciprocal fashion, at least in males. GHRH promotes sleep and GH and inhibits
      hypothalamo-pituitary-adrenocortical (HPA) hormones. CRH exerts opposite effects.
      In women, a sexual dimorphism was found because GHRH impairs sleep and stimulates
      HPA hormones. Sleep deprivation (SD) is the most powerful stimulus for inducing
      sleep. Studies in rodents show a key role of GHRH in sleep promotion after SD.
      The effects of GHRH and CRH on sleep-endocrine activity during the recovery night
      after SD are unknown. We compared sleep EEG, GH, and cortisol secretion between
      nights before and after 40 h of SD in 48 normal women and men aged 19-67 yr.
      During the recovery night, GHRH, CRH, or placebo were injected repetitively.
      After placebo during the recovery night, non-rapid-eye-movement sleep (NREMS) and
      rapid-eye-movement sleep (REMS) increased and wakefulness decreased compared with
      the baseline night. After GHRH, the increase of NREMS and the decrease of
      wakefulness were more distinct than after placebo. Also, after CRH, NREMS
      increased higher than after placebo, and a positive correlation was found between
      age and the baseline-related increase of slow-wave sleep. REMS increased after
      placebo and after GHRH, but not after CRH. EEG spectral analysis showed increases
      in the lower frequencies and decreases in the higher frequencies during NREMS
      after each of the treatments. Cortisol and GH did not differ between baseline and
      recovery nights after placebo. After GHRH, GH increased and cortisol decreased.
      Cortisol increased after CRH. No sex differences were found in these changes. Our
      data suggest that GHRH and CRH augment NREMS promotion after SD. Marked
      differences appear to exist in peptidergic sleep regulation between spontaneous
      and recovery sleep.

PMID- 16912061
TI  - Growth hormone and IGF-I modulate local cerebral glucose utilization and ATP
      levels in a model of adult-onset growth hormone deficiency.
AB  - Decreases in plasma IGF-I levels that occur with age have been hypothesized to
      contribute to the genesis of brain aging. However, support for this hypothesis
      would be strengthened by evidence that growth hormone (GH)/IGF-I deficiency in
      young animals produces a phenotype similar to that found in aged animals. As a
      result, we developed a unique model of adult-onset GH/IGF-I deficiency by using
      dwarf rats specifically deficient in GH and IGF-I. The deficiency in plasma IGF-I
      is similar to that observed with age (e.g., 50% decrease), and replacement of GH
      restores levels of IGF-I to that found in young animals with normal GH levels.
      The present study employs this model to investigate the effects of circulating GH
      and IGF-I on local cerebral glucose utilization (LCGU). Analysis of LCGU
      indicated that GH/IGF-I-deficient animals exhibit a 29% decrease in glucose
      metabolism in many brain regions, especially those involved in hippocampally
      dependent processes of learning and memory. Similarly, a high correlation between
      plasma IGF-I levels and glucose metabolism was found in these areas. The
      deficiency in LCGU was not associated with alterations in GLUT1, GLUT3, or
      hexokinase activity. A 15% decrease in ATP levels was also found in hippocampus
      of GH-deficient animals, providing compelling data that circulating GH and IGF-I
      have significant effects on the regulation of glucose utilization and energy
      metabolism in the brain. Furthermore, our results provide important data to
      support the conclusion that deficiencies in circulating GH/IGF-I contribute to
      the genesis of brain aging.

PMID- 16912062
TI  - Endothelin and calciotropic hormones share regulatory pathways in multidrug
      resistance protein 2-mediated transport.
AB  - The kidney of vertebrates plays a key role in excretion of endogenous waste
      products and xenobiotics. Active secretion in the proximal nephron is at the
      basis of this excretion, mediated by carrier proteins including multidrug
      resistance protein 2 (Mrp2). We previously showed that Mrp2 function is reduced
      by endothelin-1 (ET-1) through a basolateral B-type receptor, nitric oxide (NO),
      cGMP, and PKC (Notenboom S, Miller DS, Smits P, Russel FGM, Masereeuw R. Am J
      Physiol Renal Physiol 282: F458-F464, 2002; Notenboom S, Miller DS, Smits P,
      Russel FG, Masereeuw R. Am J Physiol Renal Physiol 287: F33-F38, 2004). This
      pathway was rapidly activated by several nephrotoxicants and appeared to be
      calcium dependent. In the present study, we studied the effect of the
      calciotropic hormones parathyroid hormone (PTH), PTH-related protein (PTHrP), and
      stanniocalcin (STC) to interfere with ET-regulated Mrp2 transport. Like ET-1, PTH
      reduces Mrp2-mediated transport by 40% in killifish renal proximal tubules. When
      given in combination, an additive effect was seen, which is partially reversed by
      the PKC inhibitor calphostin C. Recombinant PTHrP shows a comparable inhibitory
      effect, which is concentration dependent and additive to the inhibition by ET.
      STC fully reverses PTHrP-inhibited transport as does a guanylyl cyclase
      inhibitor. Finally, to confirm PTHrP bioactivity in a homologous assay, we
      performed immunolocalization and transport studies in sea bream kidney tubules.
      Mrp2 immunoreactivity was observed in approximately 40% of the tubules and is
      associated with the brush-border and apical plasma membrane of cells. Both
      proximal tubules and distal (collecting) tubules express the antigen. A highly
      significant 40% inhibition of Mrp2-mediated transport was observed with PTHrP in
      sea bream tubules. In conclusion, ET-regulated Mrp2 transport is influenced by
      calciotropic hormones and involves PKC and cGMP signaling.

PMID- 16912063
TI  - Use of a hanging-weight system for isolated renal artery occlusion during
      ischemic preconditioning in mice.
AB  - Renal failure from ischemia contributes to morbidity and mortality. Ischemic
      preconditioning (IP) represents a powerful strategy for kidney protection, and
      recent advances in transgenic mice may help elucidate its molecular mechanisms.
      However, murine IP is technically challenging and experimental details
      significantly influence results. Thus we developed a novel model for renal IP
      using a hanging-weight system for isolated renal artery occlusion. In contrast to
      previous models, this technique eliminates the need for clamping the vascular
      pedicle (artery/vein). In fact, assessment of renal injury after different time
      periods of ischemia (10-60 min) revealed highly reproducible increases in plasma
      creatinine and potassium levels, while creatinine clearance, urinary flow and
      potassium/sodium excretion were significantly attenuated. Using different numbers
      of IP cycles, we found maximal protection with four cycles of 4 min of ischemia
      reperfusion. In contrast, no significant renal protection was observed with IP of
      the vascular pedicle. To assess transcriptional responses in this model, we
      isolated RNA from preconditioned kidneys and found time-dependent induction of
      erythropoietin mRNA and plasma levels with IP. Taken together, this model
      provides highly reproducible renal injury and protection by IP, thus minimizing
      variability associated with previous techniques based on clamping of the renal
      pedicle. Further studies on renal ischemia/IP in mice may consider this
      technique.

PMID- 16912064
TI  - Maintained ENaC trafficking in aldosterone-infused rats during mineralocorticoid
      and glucocorticoid receptor blockade.
AB  - Aldosterone induces redistribution of epithelial sodium channel (ENaC) to the
      apical plasma membrane from intracellular vesicles in renal connecting tubule
      (CNT) and cortical collecting duct (CCD). The role of the classical
      mineralocorticoid receptor (MR) in ENaC trafficking is still debated. We examined
      whether the MR antagonist spironolactone affects ENaC regulation in the kidney
      cortex of aldosterone-infused rats. Aldosterone infusion for 7 days resulted in a
      plasma aldosterone concentration in the high physiological range (3 to 4 nM).
      Aldosterone infusion decreased plasma K(+) concentration compared with untreated
      control rats. Cotreatment with spironolactone completely blocked the aldosterone
      induced decrease in plasma K(+). Immunoblotting and immunohistochemistry showed
      increased protein abundance of Na-K-ATPase alpha(1)-subunit and NCC in the kidney
      cortex, in response to aldosterone infusion that was blocked by spironolactone.
      In contrast, aldosterone-induced redistribution of ENaC subunits from the
      cytoplasm to the apical plasma membrane domain in CNT and CCD was unaffected by
      spironolactone. Immunoblotting of alphaENaC showed increased protein abundance in
      aldosterone-infused rats that was not blocked by spironolactone treatment. To
      exclude possible glucocorticoid receptor (GR)-mediated effects of aldosterone, we
      treated aldosterone-infused rats with both spironolactone and the GR antagonist
      RU486. Combined MR and GR blockade prevented neither ENaC trafficking nor the
      upregulation of alphaENaC protein abundance in aldosterone-infused rats. We
      provide new evidence for ENaC trafficking occurring independent of MR and GR
      activation in aldosterone-infused rats.

PMID- 16912065
TI  - Vasa recta voltage-gated Na+ channel Nav1.3 is regulated by calmodulin.
AB  - Rat descending vasa recta (DVR) express a tetrodotoxin (TTX)-sensitive voltage
      operated Na(+) (Na(V)) conductance. We examined expression of Na(V) isoforms in
      DVR and tested for regulation of Na(V) currents by calmodulin (CaM). RT-PCR in
      isolated permeabilized DVR using degenerate primers targeted to TTX-sensitive
      isoforms amplified a product whose sequence identified only Na(V)1.3. Immunoblot
      of outer medullary homogenate verified Na(V)1.3 expression, and fluorescent
      immunochemistry showed Na(V)1.3 expression in isolated vessels. Immunochemistry
      in outer medullary serial sections confirmed that Na(V)1.3 is confined to alpha
      smooth muscle actin-positive vascular bundles. Na(V)1.3 possesses a COOH-terminal
      CaM binding motifs. Using pull-down assays and immunoprecipitation experiments,
      we verified that CaM binds to either full-length Na(V)1.3 or a GST-Na(V)1.3 COOH
      terminal fusion protein. In patch-clamp experiments, Na(V) currents were
      suppressed by calmodulin inhibitory peptide (CIP; 100 nM) or the CaM inhibitor N
      (6-aminohexyl)-5-chloro-1-naphthalene-sulphonamide hydrochloride (W7). Neither
      CIP nor W7 altered the voltage dependence of pericyte Na(V) currents; however,
      raising electrode free Ca(2+) from 20 to approximately 2,000 nM produced a
      depolarizing shift of activation. In vitro binding of CaM to GST-Na(V)1.3C was
      not affected by Ca(2+) concentration. We conclude that Na(V)1.3 is expressed by
      DVR, binds to CaM, and is regulated by CaM and Ca(2+). Inhibition of CaM binding
      suppresses pericyte Na(V) currents.

PMID- 16912066
TI  - Acute increases of renal medullary osmolality stimulate endothelin release from
      the kidney.
AB  - Experiments conducted in vitro suggest that high osmolality stimulates endothelin
      production and release by renal tubular epithelial cells. Whether hyperosmotic
      solutions exert similar effects in vivo is unknown. Therefore, we tested the
      hypothesis that increasing renal medullary osmolality enhances urinary excretion
      of endothelin in anesthetized rats. Isosmotic NaCl (284 mosmol/kgH(2)O) was
      infused either intravenously (1.5 ml/h) or into the renal medullary interstitium
      (0.5 ml/h) during a 1-h equilibration period and 30-min baseline urine collection
      period, followed by either isosmotic or hyperosmotic NaCl (921 or 1,664
      mosmol/kgH(2)O iv; 1,714 mosmol/kgH(2)O into renal medulla) for two further 30
      min periods. Compared with isosmotic NaCl, infusion of hyperosmotic NaCl into the
      renal medulla significantly increased the endothelin excretion rate (P < 0.05;
      from 0.30 +/- 0.02 to 0.49 +/- 0.03 fmol/min). Intravenous infusion of
      hyperosmotic NaCl also significantly increased endothelin excretion rate in a
      concentration-dependent manner (from 0.79 +/- 0.07 to 1.77 +/- 0.16 fmol/min and
      0.59 +/- 0.04 to 1.11 +/- 0.08 fmol/min for 1,664 and 921 mosmol/kgH(2)O,
      respectively). To differentiate between effects of osmolality and NaCl, similar
      experiments were performed using mannitol solutions. Compared with isosmotic
      mannitol, medullary interstitial infusion of hyperosmotic mannitol (1,820
      mosmol/kgH(2)O) significantly increased endothelin excretion rate (P < 0.05; from
      0.54 +/- 0.03 to 0.94 +/- 0.12 fmol/min). Thus exposing the renal medulla to
      hyperosmotic concentrations of either NaCl or mannitol stimulates endothelin
      release in vivo, consistent with medullary osmolality being an important
      regulator of renal endothelin synthesis.

PMID- 16912067
TI  - Identification of candidate mRNAs associated with gonadotropin-induced maturation
      of murine cumulus oocyte complexes using serial analysis of gene expression.
AB  - In cultured cumulus oocyte complexes (COC), FSH induces gene transcription
      required for germinal vesicle breakdown (GVBD). Experiments were performed to
      determine the critical period when gene transcription is required for GVBD and to
      identify candidate mRNAs involved. Experiment I: murine COC were cultured 4 h in
      the presence of FSH with 5,6-dichloro-1-beta-d-ribofuranosylbenzimidazole (DRB)
      added at different intervals after the start of culture. COC cultured with FSH
      underwent GVBD (82 +/- 7%). When DRB was added at 0, 5, or 10 min after culture
      initiation, oocyte maturation was blocked (17 +/- 7, 14 +/- 6, and 21 +/- 6%
      GVBD, respectively). When DRB was added after 15, 20, or 30 min, progressively
      more COC underwent GVBD (37 +/- 6, 39 +/- 6, and 66 +/- 6%, respectively). The
      critical period of transcription required for GVBD occurred between 15 and 30 min
      after culture initiation. Experiment II: COC were cultured for 25 min in the
      presence (plusDRB) or absence (minusDRB) of DRB. SAGE libraries were generated
      from COC RNA of each treatment group. A total of 48,431 and 45,367 tags were
      sequenced for the plusDRB and minusDRB libraries, respectively. Criteria used to
      identify transcripts of interest included a total tag count of at least 10 across
      both libraries and a threefold or greater difference in expression between
      libraries. Using these criteria, 39 and 27 transcripts were identified as
      differentially expressed at the P < or = 0.01 and P </= 0.001 levels,
      respectively. Differentially expressed transcripts were classed into major
      categories that included cell growth, development, and regulation of gene
      expression. Differentially expressed transcripts represent candidates potentially
      involved in regulating maturation of murine COC.

PMID- 16912068
TI  - Genetic, sex, and diet effects on body weight and obesity in the Berlin Fat Mouse
      Inbred lines.
AB  - Mouse lines long-term selected for high fatness offer the possibility to identify
      individual genes involved in the development of obesity. The Berlin Fat Mouse
      (BFM) line has been selected for low protein content and afterward for high
      fatness. Three Berlin Fat Mouse Inbred (BFMI) lines, which are derivates of the
      selection line BFM and an unselected control line (C57BL/6; B6) were
      systematically phenotyped between 3 and 20 wk. The body weights and body
      compositions were measured on a weekly basis. We demonstrated that the BFMI lines
      dispose of more body weight, body fat mass, and body lean mass than the control
      line B6 because of a better feed efficiency in these lines. In contrast to other
      growth-selected mouse lines, the BFMI lines exhibited a general increase in body
      fat mass but only a marginal increase in body lean mass. The three BFMI lines
      also showed line- and sex-specific patterns and varied in their response to high
      fat diet. The phenotypic differences between the BFMI lines can be traced back to
      different sets of fixed alleles contributing to fat accumulation and diet-induced
      obesity. Our results demonstrate that the genetically related BFMI lines are
      novel models to study the genetic as well as the nutritional aspects of obesity.

PMID- 16912069
TI  - Analysis of the bovine neutrophil transcriptome during glucocorticoid treatment.
AB  - The objective of this study was to characterize a large portion of the bovine
      neutrophil transcriptome following treatment with the anti-inflammatory
      glucocorticoid dexamethasone (Dex). Total RNA was isolated from blood neutrophils
      of healthy cattle (5 castrated male Holsteins) immediately following cell
      purification (0 h) or after ex vivo aging for 4 h with or without added Dex.
      Additional neutrophils were cotreated with a glucocorticoid receptor (GR)
      antagonist (RU486) and Dex for 4 h. RNA was amplified, dye labeled (Cy3 or Cy5),
      and hybridized to a series of National Bovine Functional Genomics Consortium
      (NBFGC) microarrays. LOWESS data normalization followed by mixture model analyses
      showed that 11.15% of the spotted NBFGC cDNAs (2,036/18,263) were expressed in 4
      h (untreated) neutrophils. Subsequent two-step mixed-model analysis detected (P <
      or = 0.05) 1,109 differentially expressed genes, of which contrast analysis
      indicated those that were independently responsive to aging (1,064), Dex (502),
      RU486 + Dex (141), or RU486 (357). In silico analysis revealed that 416 of the
      differentially expressed genes are unknown, 59 did not cluster well based on
      known function, and 634 clustered into 20 ontological categories. Independent
      validation of differential expression was done for 14 of the putatively Dex
      responsive genes across these categories. Results showed that Dex induced rapid
      translocation of GR into the neutrophil nucleus and signaled dramatic alterations
      in expression of genes that delay apoptosis, enhance bactericidal activity, and
      promote tissue remodeling without inflammation or fibrosis. Thus these findings
      revealed hitherto unappreciated plasticity of blood neutrophils and potentially
      novel anti-inflammatory/wound-healing actions of glucocorticoids.

PMID- 16912070
TI  - The glutamate-glutamine cycle as an inducible, protective face of macrophage
      activation.
AB  - Neuronal damage in HIV infection results mainly from chronic activation of brain
      tissue and involves inflammation, oxidative stress, and glutamate-related
      neurotoxicity. Glutamate toxicity acts via two distinct pathways: an excitotoxic
      one, in which glutamate receptors are hyperactivated, and an oxidative one, in
      which cystine uptake is inhibited, resulting in glutathione depletion, oxidative
      stress, and cell degeneration. A number of studies have shown that astrocytes
      normally take up glutamate, keeping extracellular glutamate concentration low in
      the brain and preventing excitotoxicity. They, in turn, provide the trophic amino
      acid glutamine via their expression of glutamine synthetase. These protective and
      trophic actions are inhibited in HIV infection, probably as a result of the
      effects of inflammatory mediators and viral proteins. In vitro and in vivo
      studies have demonstrated that activated microglia and brain macrophages (AMM)
      express the transporters and enzymes of the glutamate cycle. This suggests that
      in addition to their recognized neurotoxic properties in HIV infection, these
      cells exhibit some neuroprotective properties, which may partly compensate for
      the inhibited astrocytic function. This hypothesis might explain the discrepancy
      between microglial activation, which occurs early in the disease, and neuronal
      apoptosis and neuronal loss, which are late events. In this review, we discuss
      the possible neuroprotective and neurotrophic roles of AMM and their
      relationships with inflammation and oxidative stress.

PMID- 16912071
TI  - Role of gp120 in dendritic cell dysfunction in HIV infection.
AB  - Only a limited fraction of circulating virions are demonstrably infectious;
      therefore, exposure to inactivated viruses may mimic the most frequent type of
      CD4-HIV interactions that occur in vivo. Several studies have recently
      underscored the crucial role that those noninfectious viruses could play in
      defective immune function in HIV-infected individuals and in particular, in the
      dysregulation of dendritic cell (DC) function. In this review, we discuss how
      interactions between DC and HIV gp120 or inactivated virus, which harbor intact
      surface gp120, lead to impaired DC function through direct (direct contact) or
      indirect mechanisms (as a consequence of primary CD4+ T cell dysregulation,
      followed by defective CD4-DC interactions). It is important that these
      functionally impaired DCs fail to give optimal signal to T cells but appear to
      favor the emergence of regulatory T cells. gp120-mediated impairment of DC
      function could therefore play an important role in the pathogenesis of HIV
      disease.

PMID- 16912072
TI  - Architecture of the vimentin cytoskeleton is modified by perturbation of the
      GTPase ARF1.
AB  - Intermediate filaments are required for proper membrane protein trafficking.
      However, it remains unclear whether perturbations in vesicular membrane transport
      result in changes in the architecture of the vimentin cytoskeleton. We find that
      treatment of cells with Brefeldin A, an inhibitor of specific stages of membrane
      transport, causes changes in the organization of vimentin filaments. These
      changes arise from movement of pre-existing filaments. Brefeldin A treatment also
      leads to alterations in the microtubule cytoskeleton. However, this effect is not
      observed in cells lacking intermediate filaments, indicating that microtubule
      bundling is downstream of perturbations in the vimentin cytoskeleton. Brefeldin A
      induced changes in vimentin architecture are probably mediated through its
      effects on ADP-ribosylation factor 1 (ARF1). Expression of a dominant-negative
      mutant of ARF1 induces BFA-like modifications in vimentin morphology. The BFA
      dependent changes in vimentin architecture occurred concurrently with the release
      of the ARF1-regulated adaptor complexes AP-3 and AP-1 from membranes and adaptor
      redistribution to vimentin networks. These observations indicate that
      perturbation of the vesicular membrane transport machinery lead to reciprocal
      changes in the architecture of vimentin networks.

PMID- 16912073
TI  - Validating Aurora B as an anti-cancer drug target.
AB  - The Aurora kinases, a family of mitotic regulators, have received much attention
      as potential targets for novel anti-cancer therapeutics. Several Aurora kinase
      inhibitors have been described including ZM447439, which prevents chromosome
      alignment, spindle checkpoint function and cytokinesis. Subsequently, ZM447439
      treated cells exit mitosis without dividing and lose viability. Because ZM447439
      inhibits both Aurora A and B, we set out to determine which phenotypes are due to
      inhibition of which kinase. Using molecular genetic approaches, we show that
      inhibition of Aurora B kinase activity phenocopies ZM447439. Furthermore, a novel
      ZM compound, which is 100 times more selective for Aurora B over Aurora A in
      vitro, induces identical phenotypes. Importantly, inhibition of Aurora B kinase
      activity induces a penetrant anti-proliferative phenotype, indicating that Aurora
      B is an attractive anti-cancer drug target. Using molecular genetic and chemical
      genetic approaches, we also probe the role of Aurora A kinase activity. We show
      that simultaneous repression of Aurora A plus induction of a catalytic mutant
      induces a monopolar phenotype. Consistently, another novel ZM-related inhibitor,
      which is 20 times as potent against Aurora A compared with ZM447439, induces a
      monopolar phenotype. Expression of a drug-resistant Aurora A mutant reverts this
      phenotype, demonstrating that Aurora A kinase activity is required for spindle
      bipolarity in human cells. Because small molecule-mediated inhibition of Aurora A
      and Aurora B yields distinct phenotypes, our observations indicate that the
      Auroras may present two avenues for anti-cancer drug discovery.

PMID- 16912074
TI  - Phospho-specific binding of 14-3-3 proteins to phosphatidylinositol 4-kinase III
      beta protects from dephosphorylation and stabilizes lipid kinase activity.
AB  - Phosphatidylinositol-4-kinase-IIIbeta (PI4KIIIbeta) is activated at the Golgi
      compartment by PKD-mediated phosphorylation. Subsequent mechanisms responsible
      for continuous PtdIns(4)P production at Golgi membranes and potential interaction
      partners of activated PI4KIIIbeta are unknown. Here we identify phosphoserine/
      threonine binding 14-3-3 proteins as novel regulators of PI4KIIIbeta activity
      downstream of this phosphorylation. The PI4KIIIbeta-14-3-3 interaction, evident
      from GST pulldowns, co-immunoprecipitations and bimolecular fluorescence
      complementation, was augmented by phosphatase inhibition with okadaic acid.
      Binding of 14-3-3 proteins to PI4KIIIbeta involved the PKD phosphorylation site
      Ser294, evident from reduced 14-3-3 binding to a S294A PI4KIIIbeta mutant.
      Expression of dominant negative 14-3-3 proteins resulted in decreased PI4KIIIbeta
      Ser294 phosphorylation, whereas wildtype 14-3-3 proteins increased phospho
      PI4KIIIbeta levels. This was because of protection of PI4KIIIbeta Ser294
      phosphorylation from phosphatase-mediated dephosphorylation. The functional
      significance of the PI4KIIIbeta-14-3-3 interaction was evident from a reduction
      of PI4KIIIbeta activity upon dominant negative 14-3-3 protein expression. We
      propose that 14-3-3 proteins function as positive regulators of PI4KIIIbeta
      activity by protecting the lipid kinase from active site dephosphorylation,
      thereby ensuring a continuous supply of PtdIns(4)P at the Golgi compartment.

PMID- 16912075
TI  - Ubiquitylation-independent ER-associated degradation of an AE1 mutant associated
      with dominant hereditary spherocytosis in cattle.
AB  - Various mutations in the AE1 (anion exchanger 1, band 3) gene cause dominant
      hereditary spherocytosis, a common congenital hemolytic anemia associated with
      deficiencies of AE1 of different degrees and loss of mutant protein from red
      blood cell membranes. To determine the mechanisms underlying decreases in AE1
      protein levels, we employed K562 and HEK293 cell lines and Xenopus oocytes
      together with bovine wild-type AE1 and an R664X nonsense mutant responsible for
      dominant hereditary spherocytosis to analyze protein expression, turnover, and
      intracellular localization. R664X-mutant protein underwent rapid degradation and
      caused specifically increased turnover and impaired trafficking to the plasma
      membrane of the wild-type protein through hetero-oligomer formation in K562
      cells. Consistent with those observations, co-expression of mutant and wild-type
      AE1 reduced anion transport by the wild-type protein in oocytes. Transfection
      studies in K562 and HEK293 cells revealed that the major pathway mediating
      degradation of both R664X and wild-type AE1 employed endoplasmic reticulum (ER)
      associated degradation through the proteasomal pathway. Proteasomal degradation
      of R664X protein appeared to be independent of both ubiquitylation and N
      glycosylation, and aggresome formation was not observed following proteasome
      inhibition. These findings indicate that AE1 R664X protein, which is associated
      with dominant hereditary spherocytosis, has a dominant-negative effect on the
      expression of wild-type AE1.

PMID- 16912076
TI  - Paternal chromosome segregation during the first mitotic division determines
      Wolbachia-induced cytoplasmic incompatibility phenotype.
AB  - The most common Wolbachia-induced phenotype in insects is cytoplasmic
      incompatibility (CI), which occurs when sperm from infected males fertilize eggs
      from uninfected females. CI produces distinct phenotypes in three closely related
      haplo-diploid species of the genus Nasonia: mortality in N. longicornis and N.
      giraulti, and conversion to male development in N. vitripennis. We demonstrate
      that the majority of CI-induced mortality occurs during embryogenesis and that
      the pattern of paternal chromosome segregation during the first mitosis is a good
      predictor of CI phenotype. In N. giraulti and N. longicornis, the paternal
      chromosomes mis-segregate, producing abnormal nuclei connected by chromatin
      bridges. Consequently, these embryos arrest development with very few and
      abnormal nuclei. In contrast, the paternal genome in N. vitripennis is either not
      segregated or mis-segregates to one of the two daughter nuclei. Consequently,
      these embryos continue development utilizing the maternally derived haploid
      nuclei, resulting in male offspring. The latter class is the first documented
      example of asymmetric mitotic segregation of abnormal chromosomes. We conclude
      that in haplo-diploids, CI-induced embryonic lethality occurs only when abnormal
      paternal genome segregation affects both products of the first mitotic division.
      This is the first study to associate differences in types of CI with specific
      cytological defects.

PMID- 16912077
TI  - Structure and function of nucleus-vacuole junctions: outer-nuclear-membrane
      targeting of Nvj1p and a role in tryptophan uptake.
AB  - Nvj1p resides in the outer nuclear membrane (ONM) and binds the vacuole membrane
      protein Vac8p to form nucleus-vacuole (NV) junctions in Saccharomyces cerevisiae.
      The induction of NVJ1 expression during starvation results in the sequestration
      of two additional binding partners, Tsc13p and Osh1p. Here, we map the domains of
      Nvj1p responsible for ONM targeting and partner binding. ONM targeting requires
      both the N-terminal signal anchor-like sequence and the topogenic membrane
      spanning domain of Nvj1p. The N-terminal signal anchor-like sequence may anchor
      Nvj1p in the ONM by bridging to the inner nuclear membrane. A region encompassing
      the membrane-spanning domain is sufficient to bind Tsc13p. Osh1p and Vac8p bind
      to distinct regions in the cytoplasmic tail of Nvj1p. Overexpression of Nvj1p in
      trp1 cells causes a growth defect in low tryptophan that is rescued by additional
      copies of TAT1 or TAT2 tryptophan permeases. Conversely, nvj1-Delta trp1 cells
      grow faster than NVJ1+ trp1 cells in limiting tryptophan. Importantly, deleting
      the Osh1p-binding domain of Nvj1p abrogates the tryptophan transport-related
      growth defect of Nvj1p-overexpressing cells. Therefore, the Nvj1p-dependent
      sequestration of Osh1p negatively regulates tryptophan uptake from the medium,
      possible by affecting the trafficking of tryptophan permeases to the plasma
      membrane.

PMID- 16912078
TI  - Effects of interphase and mitotic phosphorylation on the mobility and location of
      nucleolar protein B23.
AB  - B23 (or nucleophosmin, NPM) is a multifunctional protein involved in ribosome
      biogenesis, control of centrosome duplication and in sensing cellular stress. It
      is phosphorylated during interphase by casein kinase 2 (CK2) and during mitosis
      by cyclin-dependent kinase (CDK). In this study we have addressed the role of
      these phosphorylation events in the dynamics and location of protein B23.
      Mutation of the CK2 phosphorylation site to alanine results in slower recovery of
      the mutant compared with the wild-type protein as measured by fluorescence
      recovery after photobleaching (FRAP). Immunofluorescence studies using an
      antibody against phosphorylated Thr199 revealed that B23 is phosphorylated at
      this CDK1 site at the start of mitosis and is dephosphorylated during anaphase.
      The CDK1-type phosphorylation sites are in the nucleic acid binding region of B23
      and may contribute to its dissociation from the nucleolus during mitosis. A Thr
      to Glu mutant of the CDK1-type sites as well as other members of the
      nucleoplasmin family that lack the C-terminal nucleic-acid-binding region showed
      a greater mobility and/or faster recovery than wild-type B23.1, the longer
      variant. These results provide evidence that phosphorylation at these sites
      reduces the affinity of B23 for nucleolar components and might be a factor in
      regulating its location during the cell cycle.

PMID- 16912079
TI  - Inactivation of MAPK in mature oocytes triggers progression into mitosis via a
      Ca2+ -dependent pathway but without completion of S phase.
AB  - Unfertilized sea urchin eggs that are arrested at G1 phase after completion of
      meiosis contain a highly phosphorylated mitogen-activated protein (MAP) kinase
      (MAPK), the ERK-like protein (ERK-LP). Several data including our previous
      results show that ERK-LP is inactivated after fertilization, which agrees with
      results obtained in other species including Xenopus, starfish and mammals. The
      question is to elucidate the function of a high MAPK activity in sea urchin eggs.
      We report here that dephosphorylation of ERK-LP with very low concentrations of
      two MEK inhibitors, PD98059 or U0126, triggers entry into mitosis. Under these
      conditions, recurrent oscillations of the phosphorylation of ERK-LP and of a
      tyrosine residue in Cdc2 occur, and the intracellular Ca2+ level (Ca2+ i)
      progressively and slowly increases. Nuclear envelope breakdown and all mitotic
      events initiated after dephosphorylation of ERK-LP are inhibited when changes in
      Ca2+ i are prevented; however, they are independent of the intracellular pH.
      These results suggest that inactivation of a MEK-ERK pathway, normally induced
      after fertilization of sea urchin eggs, triggers entry into mitosis by altering
      Ca2+ i but cannot trigger full DNA replication. We discuss the hypothesis that
      neither inactivation nor activation of a MEK-ERK pathway is required for S phase
      completion in sea urchin egg.

PMID- 16912080
TI  - Mechanism of polarized protrusion formation on neuronal precursors migrating in
      the developing chicken cerebellum.
AB  - Directed cell migration results from the polarization of the cellular motile
      apparatus by integration of extracellular signals, which are presented in a three
      dimensional, spatiotemporal manner in living organisms. To investigate the
      mechanism underlying the highly polarized and directional nature of migration in
      vivo, we have developed an imaging system for observing rhombic lip cell
      migration in the developing chicken cerebellum. First, we show that Cdc42 is the
      central regulator of the overall polarity, morphology and protrusion formation in
      these cells. However, perturbation of canonical polarity effectors of Cdc42, e.g.
      the Par6-Par3-aPKC complex, does not disrupt the cell asymmetry, whereas it
      affects orientation of the tip of the leading process. In contrast to Cdc42, Rac
      is required for the generation of protrusions but not the overall polarity.
      Function interference of class IA phosphoinositide 3-kinase abrogates both
      directional extension and maintenance of the long leading process, whereas PTEN
      modulates the size of the protrusion. Actomyosin contractility is important for
      coordinated spreading of the tip of the leading process in situ. Finally, ErbB4
      functions in the generation of protrusions on the rhombic lip cells. These
      results suggest that polarized protrusion formation on neuronal precursors may
      occur by a more divergent and complex mechanism than that seen in studies of
      other cell types growing on planar substrates.

PMID- 16912081
TI  - An Ins(1,4,5)P3 receptor in Paramecium is associated with the osmoregulatory
      system.
AB  - In the ciliate Paramecium, a variety of well characterized processes are
      regulated by Ca2+, e.g. exocytosis, endocytosis and ciliary beat. Therefore,
      among protozoa, Paramecium is considered a model organism for Ca2+ signaling,
      although the molecular identity of the channels responsible for the Ca2+ signals
      remains largely unknown. We have cloned - for the first time in a protozoan - the
      full sequence of the gene encoding a putative inositol (1,4,5)-trisphosphate
      (Ins(1,4,5)P3) receptor from Paramecium tetraurelia cells showing molecular
      characteristics of higher eukaryotic cells. The homologously expressed
      Ins(1,4,5)P3-binding domain binds [3H]Ins(1,4,5)P3, whereas antibodies
      unexpectedly localize this protein to the osmoregulatory system. The level of
      Ins(1,4,5)P3-receptor expression was reduced, as shown on a transcriptional level
      and by immuno-staining, by decreasing the concentration of extracellular Ca2+
      (Paramecium cells rapidly adjust their Ca2+ level to that in the outside medium).
      Fluorochromes reveal spontaneous fluctuations in cytosolic Ca2+ levels along the
      osmoregulatory system and these signals change upon activation of caged
      Ins(1,4,5)P3. Considering the ongoing expulsion of substantial amounts of Ca2+ by
      the osmoregulatory system, we propose here that Ins(1,4,5)P3 receptors serve a
      new function, i.e. a latent, graded reflux of Ca2+ to fine-tune [Ca2+]
      homeostasis.

PMID- 16912082
TI  - Epidermal and craniofacial defects in mice overexpressing Klf5 in the basal layer
      of the epidermis.
AB  - Kruppel-like factor5 (Klf5) is a zinc-finger transcription factor normally
      expressed in the skin. Here, we show that overexpression of Klf5 in the basal
      layer of the epidermis during embryogenesis affects epidermal development and
      disrupts epithelial-mesenchymal interactions necessary for skin adnexae formation
      as well as craniofacial morphogenesis. The transgenic mice exhibited exencephaly,
      craniofacial defects, persistent abdominal herniation and ectodermal dysplasia.
      Moreover, the epidermis was hypoplastic and underwent abnormal differentiation
      with expression of keratin8, a marker for single-layered epithelia, in the
      stratified epidermis. Correspondingly, we observed a downregulation of DeltaNp63
      expression in the skin. Overexpression of Klf5 in adult mice led to
      hyperkeratosis, follicle occlusion and epidermal erosions. Further, we observed
      decrease and even loss of the stem cell population of bulge keratinocytes, as
      characterized by the expression pattern of alpha6 integrin and CD34 markers. Our
      data suggest a new role of Klf5 as a modulator of p63 expression and the
      differentiation program of epidermal cells relevant for regenerative potential of
      the epidermis and epithelial-mesenchymal interactions.

PMID- 16912083
TI  - Mobile phone use and acoustic neuroma risk in Japan.
AB  - OBJECTIVES: The rapid increase of mobile phone use has increased public concern
      about its possible health effects in Japan, where the mobile phone system is
      unique in the characteristics of its signal transmission. To examine the relation
      between mobile phone use and acoustic neuroma, a case-control study was
      initiated. METHODS: The study followed the common, core protocol of the
      international collaborative study, INTERPHONE. A prospective case recruitment was
      done in Japan for 2000-04. One hundred and one acoustic neuroma cases, who were
      30-69 years of age and resided in the Tokyo area, and 339 age, sex, and residency
      matched controls were interviewed using a common computer assisted personal
      interview system. Education and marital status adjusted odds ratio was calculated
      with a conditional logistic regression analysis. RESULTS: Fifty one cases (52.6%)
      and 192 controls (58.2%) were regular mobile phone users on the reference date,
      which was set as one year before the diagnosis, and no significant increase of
      acoustic neuroma risk was observed, with the odds ratio (OR) being 0.73 (95% CI
      0.43 to 1.23). No exposure related increase in the risk of acoustic neuroma was
      observed when the cumulative length of use (<4 years, 4-8 years, >8 years) or
      cumulative call time (<300 hours, 300-900 hours, >900 hours) was used as an
      exposure index. The OR was 1.09 (95% CI 0.58 to 2.06) when the reference date was
      set as five years before the diagnosis. Further, laterality of mobile phone use
      was not associated with tumours. CONCLUSIONS: These results suggest that there is
      no significant increase in the risk of acoustic neuroma in association with
      mobile phone use in Japan.

PMID- 16912084
TI  - Respiratory health and individual estimated exposure to traffic-related air
      pollutants in a cohort of young children.
AB  - OBJECTIVES: To estimate long-term exposure to traffic-related air pollutants on
      an individual basis and to assess adverse health effects using a combination of
      air pollution measurement data, data from geographical information systems (GIS)
      and questionnaire data. METHODS: 40 measurement sites in the city of Munich,
      Germany were selected at which to collect particulate matter with a 50% cut-off
      aerodynamic diameter of 2.5 microm (PM2.5) and to measure PM2.5 absorbance and
      nitrogen dioxide (NO2). A pool of GIS variables (information about street length,
      household and population density and land use) was collected for the Munich
      metropolitan area and was used in multiple linear regression models to predict
      traffic-related air pollutants. These models were also applied to the birth
      addresses of two birth cohorts (German Infant Nutritional Intervention Study
      (GINI) and Influence of Life-style factors on the development of the Immune
      System and Allergies in East and West Germany (LISA)) in the Munich metropolitan
      area. Associations between air pollution concentrations at birth address and 1
      year and 2-year incidences of respiratory symptoms were analysed. RESULTS: The
      following means for the estimated exposures to PM2.5, PM2.5 absorbance and NO2
      were obtained: 12.8 microg/m3, 1.7x10(-5) m(-1) and 35.3 mug/m3, respectively.
      Adjusted odds ratios (ORs) for wheezing, cough without infection, dry cough at
      night, bronchial asthma, bronchitis and respiratory infections indicated positive
      associations with traffic-related air pollutants. After controlling for
      individual confounders, significant associations were found between the pollutant
      PM2.5 and sneezing, runny/stuffed nose during the first year of life (OR 1.16,
      95% confidence interval 1.01 to 1.34) Similar effects were observed for the
      second year of life. These findings are similar to those from our previous
      analysis that were restricted to a subcohort in Munich city. The extended study
      also showed significant effects for sneezing, running/stuffed nose. Additionally,
      significant associations were found between NO2 and dry cough at night (or
      bronchitis) during the first year of life. The variable "living close to major
      roads" (<50 m), which was not analysed for the previous inner city cohort with
      birth addresses in the city of Munich, turned out to increase the risk of
      wheezing and asthmatic/spastic/obstructive bronchitis. CONCLUSIONS: Effects on
      asthma and hay fever are subject to confirmation at older ages, when these
      outcomes can be more validly assessed.

PMID- 16912085
TI  - Risk of tuberculin conversion among healthcare workers and the adoption of
      preventive measures.
AB  - BACKGROUND: In industrialised countries, occupational tuberculosis among
      healthcare workers (HCWs) is re-emerging as an important public health issue. To
      prevent and control tuberculosis transmission, several institutions have issued
      and implemented recommendations and practice guidelines. OBJECTIVES: To estimate
      the annual rate of tuberculosis infection (ARTI; per 100 person-years) among HCWs
      in Turin, the capital of the Piedmont region of Italy, to identify factors
      associated with variations in the ARTI and to evaluate the efficacy of the
      regional guidelines to prevent and control tuberculosis. METHODS: The study was
      conducted between 1997 and 2004 on a cohort of HCWs. The tuberculosis infection
      was diagnosed through tuberculin skin testing (TST) conversion and defined as an
      induration increase of at least 10 mm from a previous negative TST. The ARTI and
      the hazard ratio for each at-risk subgroup, categorised according to working
      activities and settings, was estimated using exponential survival models. The
      efficacy of the regional guidelines was estimated by stratifying the analysis
      according to the moment of the implementation of the guidelines (before/after).
      RESULTS: The 2182 study participants were drawn from the dynamic cohort. The
      overall adjusted ARTI was 1.6 (95% CI: 1.3 to 1.9)/100 person-years. Different
      workplaces (eg, administrative and infectious diseases inpatient services) and
      occupations (eg, clerical and medical workers) were associated with significantly
      different ARTIs, ranging between 0.62 and 2.62 and between 0.61 and 1.71,
      respectively, whereas the TST conversion risk differed by about 16-68% and 30
      60%, respectively. The implementation of the guidelines coincided with overall
      ARTI reductions of 1.3/100 person-years, and concurrently the variations between
      ARTIs of different occupations and workplaces disappeared. CONCLUSIONS: The
      occupational risk categories for targeting the surveillance and prevention of
      tuberculosis transmission among HCWs were identified, and the introduction of
      preventive measures was observed to be effective in decreasing the overall risk
      of tuberculosis infection among HCWs.

PMID- 16912086
TI  - Occupational and other risk factors for hand-grip strength: the Honolulu-Asia
      Aging Study.
AB  - BACKGROUND: In certain occupations, including farm work, workers are exposed to
      hazardous substances, some of which are known to be toxic to the nervous system
      and may adversely affect muscle strength. Measurement of hand-grip strength may
      be useful for detecting neurotoxic exposure. METHODS: The authors studied 3522
      participants of the Honolulu Heart Program and the Honolulu-Asia Aging Study to
      determine whether occupational exposures to pesticides, solvents, and metals
      assessed at exam I (1965-68) are associated with hand-grip strength at exam IV
      (1991-93) and change in hand-grip strength over 25 years. Correlation, analysis
      of variance and covariance, and linear regression were used to evaluate the
      associations. RESULTS: At exam IV, participants ranged in age from 71-93 years;
      mean hand-grip strength was 39.6 kg at exam I and 30.3 kg at exam IV. Over 25
      years, the decline in hand-grip strength was an average of 8-9 kg for all
      exposures. Hand-grip strength was inversely associated with age and glucose but
      directly associated with cognitive function, BMI, and haemoglobin level. No other
      exposures were associated with hand-grip strength. CONCLUSION: This study did not
      provide evidence that occupational exposure to pesticides, solvents, and metals
      adversely affected hand-grip strength in this population, but confirmed other
      important associations with hand-grip strength.

PMID- 16912087
TI  - A case-control study of farming and prostate cancer in African-American and
      Caucasian men.
AB  - OBJECTIVE: To determine the risk of prostate cancer associated with farming by
      duration, recency and specific activities among African-Americans and Caucasians.
      METHODS: This population-based case-control study had information on farming
      related activities for 405 incident prostate cancer cases and 392 controls
      matched for age, race and region in South Carolina, USA, from 1999 to 2001. Cases
      with histologically confirmed, primary invasive prostate cancer who were aged
      between 65 and 79 years were ascertained through the South Carolina Central
      Cancer Registry. Appropriately matched controls were identified from the Health
      Care Financing Administration Medicare Beneficiary File. Data were collected
      using computer-assisted telephone interviewing, and adjusted odds ratios (aOR)
      were estimated using unconditional logistic regression. RESULTS: Farming was
      associated with increased risk of prostate cancer in Caucasians (aOR 1.8; 95%
      confidence interval (CI) 1.3 to 2.7) but not in African-Americans (aOR 1.0; 95%
      CI 0.6 to 1.6). Regarding specific farming activities, farmers who mixed or
      applied pesticides had a higher risk of prostate cancer (aOR 1.6; 95% CI 1.2 to
      2.2). Increased risk of prostate cancer was observed only for those farming <5
      years. CONCLUSIONS: Increased risk of prostate cancer for farmers in this study
      may be attributable to pesticide exposure. Racial differences in the association
      between farming and prostate cancer may be explained by different farming
      activities or different gene-environment interactions by race.

PMID- 16912088
TI  - Rectal cancer and exposure to metalworking fluids in the automobile manufacturing
      industry.
AB  - BACKGROUND: Rectal cancer has been previously associated with exposure to
      metalworking fluids in a cohort mortality study of autoworkers. OBJECTIVE: To
      better specify the exposure-response relationship with straight metalworking
      fluids (mineral oils) by applying non-parametric regression methods that avoid
      linearity constraints and arbitrary exposure cut points and by lagging exposure
      to account for cancer latency, in a nested case-control analysis. METHODS: In
      addition to the classical Poisson regression with categorical exposure, survival
      models with penalised splines were used to estimate the exposure-response
      relationship between cumulative exposure to straight metalworking fluid and
      mortality from rectal cancer. Exposures to water-based metalworking fluids were
      treated as potential confounders, and all exposures were lagged by 5, 10, 15 and
      20 years to account for cancer latency. The influence of the highest exposures
      was dealt with by a log transformation and outlier removal. The sensitivity of
      the penalised splines to alternative criteria for model selection and to the
      placement of knots was also examined. RESULTS: The hazard ratio for mortality
      from rectal cancer increased essentially linearly with cumulative exposure to
      straight metalworking fluid (with narrow confidence bands) up to a maximum of 2.2
      at the 99th centile of exposure and then decreased (with wide confidence bands).
      Lagging exposure up to 15 years increased the initial steepness of the curve and
      raised the maximum hazard ratio to 3.2. CONCLUSIONS: Non-parametric smoothing of
      lagged exposures has shown stronger evidence for a causal association between
      straight metalworking fluid and rectal cancer than was previously described using
      standard analytical methods. This analysis suggests an exposure-response trend
      that is close to linear and statistically significant over most of the exposure
      range and that increases further with lagged exposures. Smoothing should be
      regularly applied to environmental studies with quantitative exposure estimates
      to refine characterisation of the dose-response relationship.

PMID- 16912089
TI  - Comparison of parental reports of smoking and residential air nicotine
      concentrations in children.
AB  - BACKGROUND: Using questionnaires to assess children's residential exposure to
      environmental tobacco smoke (ETS) may result in misclassification from recall and
      response bias. Questionnaire data have frequently been validated against urinary
      cotinine measurements, but rarely against actual measurements of residential air
      nicotine. OBJECTIVE: To compare questionnaire reported smoking with air nicotine
      concentrations in a large population of children and with urinary cotinine levels
      in a subpopulation; and to assess the potential impact of the symptom status of
      the children on the agreement between different measures of exposure. METHODS:
      The authors assessed residential exposure to ETS in 347 German, 335 Dutch, and
      354 Swedish preschool and schoolchildren by questionnaire and air nicotine
      measurements, and in a subset of 307 German children by urinary cotinine
      measurements. They then compared the different measures of ETS exposure. RESULTS:
      In all countries, air nicotine concentrations increased with increasing
      questionnaire reported smoking in a dose-response fashion. Specificity and
      negative predictive values of questionnaire reports for nicotine concentrations
      were excellent. Sensitivity and positive predictive values were moderate to good.
      Excluding occasional smokers, the overall percentage of homes misclassified was
      6.9%, 6.7%, and 5.1% in Germany, the Netherlands, and Sweden, respectively.
      Similar results were found for the agreement of urinary cotinine concentrations
      with questionnaire reports and air nicotine levels. There was no indication of
      underreporting by parents of symptomatic children. CONCLUSION: Despite some
      misclassification, questionnaire reports are an inexpensive and valid estimate of
      residential ETS exposure among preschool and school children.

PMID- 16912090
TI  - Occupational noise exposure and ischaemic heart disease mortality.
AB  - AIMS: To investigate the hypothesis that long term exposure to excessive noise
      can increase the risk of ischaemic heart disease. METHODS: A case-control design,
      nested within a cohort of nuclear power workers employed at two sites in England
      over the period 1950-98, was used. Cases were men who died from ischaemic heart
      disease (ICD-9: 410-414) aged 75 or under; each was matched to a surviving
      control of the nearest age who joined the same site at the same time. Personal
      noise exposure was assessed retrospectively for each man by hygienists using (1)
      company work histories, (2) noise survey records from 1965-98, and (3) judgements
      about likely use of hearing protection devices. Men were classified into four
      groups according to their cumulative exposure to noise, with men whose exposure
      at the company never exceeded 85dB(A) for at least one year being considered
      "unexposed". Risks were compared via odds ratios (ORs) using conditional logistic
      regression and adjusted for systolic and diastolic blood pressure, height, BMI,
      and smoking, as measured at recruitment to the company. RESULTS: Analysis was
      based on 1101 case-control pairs. There was little difference between the
      exposure groups at recruitment. There was no evidence of increased risk at site
      A: the ORs for ischaemic heart disease mortality among low, medium, and high
      exposure categories, compared to unexposed men, being 1.04, 1.00, and 0.77. The
      corresponding ORs (95% CIs) at site B were 1.15 (0.81-1.65) 1.45 (1.02-2.06), and
      1.37 (0.96-1.96). When the comparison was confined to men with at least five
      years of employment, these dropped to 1.07 (0.64-1.77), 1.33 (0.88-2.01), and
      1.21 (0.82-1.79) respectively. CONCLUSIONS: The authors did not find
      statistically robust evidence of increased risk but the estimates at site B are
      consistent with those in a major cohort study. A strength of the present study is
      that the validity of noise estimation at site B has been demonstrated elsewhere.

PMID- 16912091
TI  - Associations of traffic related air pollutants with hospitalisation for first
      acute myocardial infarction: the HEAPSS study.
AB  - BACKGROUND: Acute myocardial infarction (AMI) is the leading cause of death
      attributed to cardiovascular diseases. An association between traffic related air
      pollution and AMI has been suggested, but the evidence is still limited.
      OBJECTIVES: To evaluate in a multicentre study association between
      hospitalisation for first AMI and daily levels of traffic related air pollution.
      METHODS: The authors collected data on first AMI hospitalisations in five
      European cities. AMI registers were available in Augsburg and Barcelona; hospital
      discharge registers (HDRs) were used in Helsinki, Rome and Stockholm. NO2, CO,
      PM10 (particles <10 microm), and O3 were measured at central monitoring sites.
      Particle number concentration (PNC), a proxy for ultrafine particles (<0.1
      microm), was measured for a year in each centre, and then modelled
      retrospectively for the whole study period. Generalised additive models were used
      for statistical analyses. Age and 28 day fatality and season were considered as
      potential effect modifiers in the three HDR centres. RESULTS: Nearly 27,000 cases
      of first AMI were recorded. There was a suggestion of an association of the same
      day CO and PNC levels with AMI: RR = 1.005 (95% CI 1.000 to 1.010) per 0.2 mg/m3
      and RR = 1.005 (95% CI 0.996 to 1.015) per 10000 particles/cm3, respectively.
      However, associations were only observed in the three cities with HDR, where
      power for city-specific analyses was higher. The authors observed in these cities
      the most consistent associations among fatal cases aged <75 years: RR at 1 day
      lag for CO = 1.021 (95% CI 1.000 to 1.048) per 0.2 mg/m3, for PNC = 1.058 (95% CI
      1.012 to 1.107) per 10000 particles/cm3, and for NO2 = 1.032 (95% CI 0.998 to
      1.066) per 8 microg/m3. Effects of air pollution were more pronounced during the
      warm than the cold season. CONCLUSIONS: The authors found support for the
      hypothesis that exposure to traffic related air pollution increases the risk of
      AMI. Most consistent associations were observed among fatal cases aged <75 years
      and in the warm season.

PMID- 16912092
TI  - Correlation between the level of cytogenetic aberrations in cultured human
      lymphocytes and the age and gender of donors.
AB  - To answer whether the age-related accumulation of chromosomal damage differs in
      men and women, and whether the aberration level in centenarians is proportional
      to their age, cytogenetic aberrations in dividing cells were analyzed. G-band
      karyotyping of mitotic spreads from lymphocytes was performed in 52 Polish
      centenarians and 71 controls (aged 21-78). Statistical evaluation was performed
      using nonparametric tests and regression analysis. The average level of all
      chromosomal aberrations was comparable in centenarians of both genders, but the
      age-related increase in chromosomal damage occurred faster in women than in men.
      Aging in both genders was marked by the increasing level of all aberrations
      rather than by chromosome-specific changes; the loss of X chromosome was the
      leading contributor in women. The age-related increase in the level of
      chromosomal damage reflected accumulation of dividing cells with a small number
      of aberrations. Individuals who survive to the extreme old age appear to
      accumulate aberrations at the slower rate.

PMID- 16912093
TI  - PGC-1beta down-regulation is associated with reduced ERRalpha activity and MCAD
      expression in skeletal muscle of senescence-accelerated mice.
AB  - Mitochondrial dysfunction is involved in the development of aging. Here, we
      examined the effect of aging on the skeletal muscle expression of two isoforms of
      the transcriptional peroxisome proliferator-activated receptor gamma (PPARgamma)
      coactivator-1 (PGC-1) in an experimental murine model of accelerated aging, the
      senescence-accelerated mouse (SAM). The senescence-accelerated prone mice (SAM
      P8) showed no changes in PGC-1alpha, but a decrease in PGC-1beta expression (52%
      reduction, p <.001) was observed compared to the senescence-accelerated resistant
      mice (SAM-R1). In agreement with the proposed role of PGC-1beta as an estrogen
      related receptor (ERR) protein ligand, the expression of the ERRalpha target gene
      medium-chain acyl-coenzyme A dehydrogenase was strongly suppressed (85%, p <.001)
      in SAM-P8. The decrease in the expression of medium-chain acyl-coenzyme A
      dehydrogenase was consistent with the reduction in ERRalpha DNA-binding activity
      of SAM-P8. These findings indicate that the age-mediated decrease in PGC-1beta
      expression in SAM-P8 skeletal muscle affects the expression of genes involved in
      mitochondrial fatty acid oxidation.

PMID- 16912094
TI  - Calorie restriction in mice: effects on body composition, daily activity,
      metabolic rate, mitochondrial reactive oxygen species production, and membrane
      fatty acid composition.
AB  - Different levels of calorie restriction (CR) (125, 85, 50, or 40 kcal/wk for 1,
      3, and 6 months) were examined in mice by using the paradigm of Weindruch and
      colleagues. Lean and total body mass increased on 125 and 85 kcal/wk, but there
      was negligible growth on low-energy intake. There was no CR-induced reduction in
      either daily activity or mass-specific metabolic rate. There was no CR-effect on
      in vitro reactive oxygen species production by liver or muscle mitochondria at 3
      months, but after 6 months the effect was significantly reduced in liver
      mitochondria from 40 kcal/wk mice compared to 125 kcal/wk mice. Changes in the
      fatty acid composition of phospholipids from liver, kidneys, heart, brain, and
      skeletal muscle were observed following 1 month of CR.

PMID- 16912095
TI  - Hypoxia and expression of hypoxia-inducible factor in the aging kidney.
AB  - Renal senescence is characterized by interstitial fibrosis and loss of
      peritubular capillaries. In this study, we provided evidence of
      tubulointerstitial hypoxia and the operation of hypoxia-inducible factor (HIF) in
      the aging kidney. Using two distinct methods, pimonidazole immunostaining and the
      expression of the "hypoxia-responsive" reporter of the transgenic rats, we
      identified the age-related expansion of hypoxia in all areas of the kidney.
      Expansion was most prominent in the cortex. Clusters of hypoxic tubules were
      observed in the superficial cortical zones, areas adjacent to the outer nephrons
      and expanded in the medullary rays. The degree of hypoxia was positively
      correlated with the age-related tubulointerstitial injury (R(2) = 0.88, p <.01),
      which was associated with the upregulation of HIF-regulated genes, such as
      vascular endothelial growth factor (VEGF) and glucose transporter-1 (GLUT1) (real
      time polymerase chain reaction). These findings point to the involvement of
      hypoxia and highlight the pathological relevance of HIF and its target genes in
      the aging kidney.

PMID- 16912096
TI  - Protein nitration with aging in the rat semimembranosus and soleus muscles.
AB  - On the basis of the accelerated age-related effects in type II muscle, we
      hypothesized that with aging the semimembranosus (type II) muscle would
      accumulate a greater amount of oxidized proteins compared to proteins in the
      soleus (type I) muscle. In this study, 3-nitrotyrosine (3-NT) was used as a
      stable marker of protein oxidative damage. The presence of 3-NT was evaluated in
      muscles from young adult, old, and very old Fischer 344 rats to provide an
      indication of the time course of muscle protein oxidative damage. A significant
      age-associated increase in nitrotyrosine-modified proteins was observed. The
      modified proteins identified by matrix-assisted laser desorption ionization-time
      of flight (MALDI-TOF) mass spectrometry include the sarcoplasmic reticulum Ca(+2)
      ATPase, aconitase, beta-enolase, triosephosphate isomerase, and carbonic
      anhydrase III. These proteins, involved in metabolism and calcium homeostasis,
      exhibited an age-dependent increase in 3-NT content in both muscles. However,
      significant levels of 3-NT modification were present at an earlier age in the
      semimembranosus muscle.

PMID- 16912097
TI  - Of mice and monkeys: National Institute on Aging resources supporting the use of
      animal models in biogerontology research.
AB  - The preponderance of our understanding of the biological changes that occur with
      aging has come from studies using rodents. Rodents are a valuable model for
      biogerontology research because of similarities to humans in the physiology and
      cell biology of aging. There are, however, many differences between rodents and
      humans, so application of findings in rodents to human aging requires the use of
      a model that is closer to humans at the genetic and physiological level. In aging
      research, the macaque has filled this need. There are many challenges associated
      with using nonhuman primates in aging research, not the least of which are the
      limited availability of aged monkeys and the cost of using them. To facilitate
      this research, the National Institute on Aging has developed several resources to
      assist investigators and promote the use of the nonhuman primate model in aging
      research.

PMID- 16912098
TI  - Ptolemaic bathing.

PMID- 16912099
TI  - Bathing disability and the risk of long-term admission to a nursing home.
AB  - BACKGROUND: The prevalence of disability in bathing and the likelihood of a long
      term nursing home admission increase substantially with age. We performed a
      prospective study to determine whether the occurrence of persistent disability in
      bathing is associated with the risk of a long-term nursing home admission,
      independent of potential confounders, including persistent disability in other
      essential activities of daily living. METHODS: We studied 754 community-living
      persons, 70 years old or older, who were nondisabled in four essential activities
      of daily living. Participants were followed with monthly telephone interviews for
      a median of 75 months to determine the occurrence of persistent (i.e., present
      for at least 2 consecutive months) disability in bathing and the time to the
      first long-term nursing home admission, defined as longer than 3 months. RESULTS:
      One hundred thirteen (15.0%) participants had a long-term nursing home admission.
      At least one episode of persistent bathing disability occurred among 59 (52.2%)
      participants with a long-term nursing home admission and 210 (32.8%) without a
      long-term admission (p <.001). In a proportional hazards model that was fully
      adjusted for potential confounders, the occurrence of persistent bathing
      disability increased the risk of a long-term nursing home admission by 77%
      (hazard ratio 1.77, 95% confidence interval 1.05 to 2.98), but had no effect on
      the risk of a short-term nursing home admission (hazard ratio 0.87, 95%
      confidence interval 0.51 to 1.49). CONCLUSIONS: Among community-living older
      persons, the occurrence of persistent disability in bathing is independently
      associated with the risk of a long-term nursing home admission, but has no effect
      on short-term admissions. Interventions directed at the prevention and
      remediation of bathing disability have the potential to reduce the burden and
      expense of long-term care services.

PMID- 16912100
TI  - Variation in sources of clinician-rated and self-rated instrumental activities of
      daily living disability.
AB  - BACKGROUND: It is unclear how well self-reports and clinician ratings of
      performance in the instrumental activities of daily living (IADLs; household
      maintenance tasks) correspond and why they may differ. METHODS: We assessed
      clinician-rated IADL performance using an occupational therapy protocol, the
      Assessment of Motor and Process Skills (AMPS). AMPS and self-rated IADL
      disability were compared in two groups of nondemented elderly persons without ADL
      limitation: a group with functional limitation only (self-reported difficulty in
      some area of upper or lower body function, n = 139) and a group that reported
      functional limitation plus IADL disability (difficulty in at least one IADL task,
      n = 49). Occupational therapists were blind to self-reports, and all assessments
      were conducted in respondent homes. RESULTS: Self-rated IADL disability was
      significantly associated with the AMPS motor skill score (r = -.34, p <.001), but
      the motor skill score was only moderately sensitive (61%) and specific (67%) in
      identifying self-rated disability. In adjusted logistic regression models,
      clinician-rated performance and self-rated IADL disability shared some physical
      predictors, but only clinician-rated performance was related to cognitive status.
      AMPS process skill scores did not relate to self-rated IADL disability or
      physical or cognitive status. CONCLUSIONS: In this sample of older adults without
      dementia or ADL disability, clinician ratings of IADL motor skill and self-rated
      IADL disability were correlated. Physical deficits appear to be more salient in
      self-ratings than is cognitive ability, because cognitive ability (in particular,
      verbal fluency) was associated only with clinician-rated IADL performance.

PMID- 16912101
TI  - Falls-related self-efficacy is independently associated with balance and mobility
      in older women with low bone mass.
AB  - BACKGROUND: It is currently unknown whether falling is independently associated
      with measures of balance and mobility in older adults after accounting for
      relevant physiological functions. This cross-sectional study assessed the
      independent association of falls-related self-efficacy to balance and mobility
      after accounting for age, current physical activity, and performances in relevant
      physiological domains in 98 older women, aged 75-86 years, with low bone mass.
      METHODS: Falls-related self-efficacy was assessed by the Activities-Specific
      Balance Confidence Scale (ABC Scale). Measures of balance and mobility included
      the 13-item Community Balance and Mobility Scale (CB & M Scale) and gait speed
      under two conditions: normal-paced and fast-paced. Physiological assessment
      included postural sway, foot reaction time, dominant quadriceps and dorsiflexor
      strength, proprioception, tactile sensitivity, edge contrast sensitivity, and
      visual acuity. RESULTS: Falls-related self-efficacy was independently associated
      with both balance and mobility after accounting for age, current physical
      activity level, and performances in relevant physiological domains. Based on the
      standardized beta coefficients, the ABC Scale score was more associated with
      measures of balance and mobility than measures of physiological function.
      CONCLUSION: These results highlight the independent association of falls-related
      self-efficacy with physical performance in older women with low bone mass. Thus,
      clinicians may need to consider falls-related self-efficacy when assessing and
      treating balance and mobility in this population, and falls-related self-efficacy
      may be useful as a screening tool to identify those persons with impaired balance
      and mobility.

PMID- 16912102
TI  - Blood pressure and lower limb function in older persons.
AB  - BACKGROUND: Factors contributing to gait difficulties in elderly persons are
      considered to be multifactorial and are not well understood. The purpose of this
      study was to examine the association of blood pressure (BP) with change in lower
      limb function in older persons. METHODS: Eight hundred eighty-eight older
      Catholic clergy members without baseline dementia or Parkinson's disease were
      recruited from about 40 groups across the United States. At baseline, BP was
      measured, the presence of vascular diseases and diabetes was recorded, cognitive
      function was assessed, and medications were inspected. At baseline and subsequent
      annual visits, gait and balance were assessed using performance-based tasks from
      which a previously established composite measure of lower limb function was
      derived. RESULTS: In a general estimating equation analysis controlling for age,
      education, and gender, a 10 mmHg increment in systolic blood pressure (SBP) was
      associated with greater decline in lower limb function (estimate of interaction =
      -6.35 x 10(-3), standard error = 2.49 x 10(-3), p =.011). Thus, on average, lower
      limb function declined 28.7% faster in persons with an SBP of 160 mmHg than in
      persons with an SBP of 120 mmHg. This effect was unchanged after controlling for
      baseline vascular diseases, diabetes, or cognition. However, censoring
      individuals who developed stroke during the study made the relationship between
      SBP and change in lower limb function nonsignificant. CONCLUSIONS: SBP may be
      associated with decline in lower limb function in older persons.

PMID- 16912103
TI  - The impact of health status on physicians' intentions to offer cancer screening
      to older women.
AB  - BACKGROUND: Screening for breast and cervical cancer reduces disease-specific
      mortality, but high rates of comorbidity and disability among elderly persons may
      alter the risks and benefits of screening. METHODS: We performed a mail survey of
      primary care physicians to estimate the impact of health status on physicians'
      intentions to offer cancer screening to older women. Respondents were asked to
      read a scenario about an older woman. Each scenario patient was one of three ages
      (70, 80, or 90) and had one of three levels of comorbidity and disability.
      Respondents were asked to estimate the likelihood of offering screening with
      mammography and Pap smear to these patients on a 5-point Likert scale. A logistic
      regression compared those physicians somewhat or very likely to offer screening
      with those less likely to do so. Further analyses examined the characteristics of
      physicians likely to "overscreen" the frailest older women (<5 years median life
      expectancy) or "underscreen" the healthiest (>10 years median life expectancy).
      RESULTS: Respondents returned 2003 completed surveys (37.4%). Controlling for age
      and prior screening, higher levels of comorbidity and disability were associated
      with a significantly lower likelihood of offering screening for both mammography
      and Pap smear. Nonetheless, a substantial percentage (30.7%) of physicians
      indicated a high likelihood of offering a frail 90-year-old woman a mammogram,
      and 13.4% would offer her a Pap smear. In general, overscreening was more common
      than underscreening. Female gender was associated with "overscreening" with
      mammography, whereas male gender and lack of board certification predicted
      "underscreening." Lack of board certification was associated with "overscreening"
      with Pap smear. CONCLUSIONS: In addition to age, primary care physicians consider
      health status in deciding to offer cancer screening to older women. Education and
      guidelines for cancer screening should more explicitly address the risks of
      overscreening among frail older women.

PMID- 16912104
TI  - Longitudinal changes in aerobic capacity: implications for concepts of aging.
AB  - BACKGROUND: Whereas aerobic capacity declines with age, major factors responsible
      for such decline have been poorly defined by past studies. METHODS: Participants
      were relatively healthy older individuals (339 women, 253 men) in whom
      demographic information and cardiopulmonary physiological measurements were
      obtained at baseline and biannually for three additional measurements. RESULTS:
      The study identified progressive declines in both forced expiratory volume in 1
      second (FEV(1)) and in maximal exercise heart rate as two variables that
      accounted primarily for the longitudinal decline of aerobic performance in this
      cohort of relatively fit older persons who achieved high respiratory exchange
      ratios (RER; mean = 1.08 for women, 1.12 for men). Whereas women achieved a peak
      oxygen consumption (VO(2peak)) only 77% that of men, oxygen uptake became similar
      to men (to 95%) when measured per kilogram of lean body mass rather than per
      kilogram of total body mass. During the 6 years of the study (four time points)
      aerobic capacity declined in both sexes, however, less steeply for women than for
      men (18% vs 24% per decade, respectively). The rate of decline was independent of
      baseline variables such as body composition (e.g., lean body mass, lean/fat
      ratio), smoking status, medications, or concomitant health conditions, even
      though these variables strongly influenced baseline aerobic performance.
      Inclusion of FEV(1) and maximal exercise heart rate into the statistical models,
      however, accounted for most of the longitudinal decline of aerobic performance.
      When adjusted for these two variables, aerobic capacity declined 9.7% and 10.4%
      per decade in women and men, respectively. CONCLUSIONS: Our findings emphasize
      the primary importance of declining FEV(1) and declining maximal exercise heart
      rate in accounting for the "aging effect" on aerobic capacity. Thus, when
      comparing longitudinal studies, all estimates of aerobic decline should be
      interpreted with respect to the specific variables included in the models, which
      also need to include FEV(1) and maximal exercise heart rate.

PMID- 16912106
TI  - Foot and ankle risk factors for falls in older people: a prospective study.
AB  - BACKGROUND: Foot problems are common in older people and are associated with
      impaired balance and functional ability. Few prospective studies, however, have
      been undertaken to determine whether foot problems are a risk factor for falls.
      METHODS: One hundred seventy-six people (56 men and 120 women, mean age 80.1,
      standard deviation 6.4 years) residing in a retirement village underwent tests of
      foot and ankle characteristics (including foot posture, range of motion,
      strength, and deformity) and physiological falls risk factors (including vision,
      sensation, strength, reaction time, and balance) and were followed for 12 months
      to determine the incidence of falls. RESULTS: Seventy-one participants (41%)
      reported falling during the follow-up period. Compared to those who did not fall,
      fallers exhibited decreased ankle flexibility, more severe hallux valgus
      deformity, decreased plantar tactile sensitivity, and decreased toe plantarflexor
      strength; they were also more likely to have disabling foot pain. Discriminant
      function analysis revealed that decreased toe plantarflexor strength and
      disabling foot pain were significantly and independently associated with falls
      after accounting for physiological falls risk factors and age. CONCLUSIONS: Foot
      and ankle problems increase the risk of falls in older people. Interventions to
      address these factors may hold some promise as a falls prevention strategy.

PMID- 16912105
TI  - Handgrip strength and cognitive decline in older Mexican Americans.
AB  - BACKGROUND: Cognitive decline and dementia are associated with disability and
      premature death in old age. We examined whether low handgrip strength predicts
      subsequent cognitive decline in older Mexican Americans. METHODS: We worked with
      a 7-year prospective cohort of 2160 noninstitutionalized Mexican Americans aged
      65 years or older from the Hispanic Established Population for the
      Epidemiological Study of the Elderly (H-EPESE) who had a Mini-Mental State
      Examination (MMSE) score > or = 21 at baseline. Measures included: (i)
      sociodemographic factors (age, gender, and education), handgrip strength, and
      near and distant visual impairment from baseline interview; and (ii) MMSE, body
      mass index (BMI), and medical conditions (stroke, heart attack, diabetes,
      depression, and hypertension) from four waves of data collection. RESULTS: Using
      general linear mixed models, we found a significant trend with scores in the
      lowest quartile of handgrip strength at baseline to be associated with lower MMSE
      scores over time (estimate = -1.28, standard error = 0.16; p <.0001). There was a
      significant handgrip Strength-by-Time interaction with MMSE scores. Participants
      in the lowest handgrip strength quartile had a greater cognitive decline over
      time (estimate = -0.26, standard error = 0.07; p <.001) than did those
      participants in the highest quartile. This association remained statistically
      significant after controlling for potential confounding factors. CONCLUSION:
      Older Mexican Americans with reduced handgrip strength at baseline demonstrated a
      statistically significant decline in cognitive function over a 7-year period. By
      contrast, participants in the highest handgrip strength quartile maintained a
      higher level of cognitive function.

PMID- 16912107
TI  - Telomeres and human somatic fitness.
AB  - Mean leukocyte telomere length may be an indicator of biological age, and as such
      it appears to provide information over and above chronological age of the risk
      for developing diseases of aging in humans. Here I propose that the mean
      leukocyte telomere length is an index of "somatic fitness," a concept that breaks
      down the artificial boundary between aging and diseases of aging. I also propose
      that, in exceptionally old humans, ultrashort leukocyte telomeres might be a
      determinant of life span.

PMID- 16912109
TI  - Polypharmacy was associated with mortality in the elderly Hispanic population:
      how strong was the association?

PMID- 16912110
TI  - MRI without the magnet.

PMID- 16912111
TI  - Our unborn children at risk?

PMID- 16912112
TI  - Identification of inflammatory gene modules based on variations of human
      endothelial cell responses to oxidized lipids.
AB  - Oxidized phospholipids are thought to promote atherogenesis by stimulating
      endothelial cells (ECs) to produce inflammatory cytokines, such as IL-8. In
      studies with mouse models, we previously demonstrated that genetic variation in
      inflammatory responses of endothelial cells to oxidized lipids contributes
      importantly to atherosclerosis susceptibility. We now show that similar
      variations occur in cultured aortic ECs derived from multiple heart transplant
      donors. These variations were stably maintained between passages and, thus,
      reflect either genetic or epigenetic regulatory differences. Expression array
      analysis of aortic EC cultures derived from 12 individuals revealed that >1,000
      genes were regulated by oxidized phospholipids. We have used the observed
      variations in the sampled population to construct a gene coexpression network
      comprised of 15 modules of highly connected genes. We show that several
      identified modules are significantly enriched in genes for known pathways and
      confirm a module enriched for unfolded protein response (UPR) genes using siRNA
      and the UPR inducer tunicamycin. On the basis of the constructed network, we
      predicted that a gene of unknown function (MGC4504) present in the UPR module is
      a target for UPR transcriptional activator ATF4. Our data also indicate that IL-8
      is present in the UPR module and is regulated, in part, by the UPR. We validate
      these by using siRNA. In conclusion, we show that interindividual variability can
      be used to group genes into pathways and predict gene-gene regulatory
      relationships, thus identifying targets potentially involved in susceptibility to
      common diseases such as atherosclerosis.

PMID- 16912113
TI  - Bestrophin-2 is a candidate calcium-activated chloride channel involved in
      olfactory transduction.
AB  - Ca-activated Cl channels are an important component of olfactory transduction.
      Odor binding to olfactory receptors in the cilia of olfactory sensory neurons
      (OSNs) leads to an increase of intraciliary Ca concentration by Ca entry through
      cyclic nucleotide-gated (CNG) channels. Ca activates a Cl channel that leads to
      an efflux of Cl from the cilia, contributing to the amplification of the OSN
      depolarization. The molecular identity of this Cl channel remains elusive. Recent
      evidence has indicated that bestrophins are able to form Ca-activated Cl channels
      in heterologous systems. Here we have analyzed the expression of bestrophins in
      the mouse olfactory epithelium and demonstrated that only mouse bestrophin-2
      (mBest2) was expressed. Single-cell RT-PCR showed that mBest2 was expressed in
      OSNs but not in supporting cells. Immunohistochemistry revealed that mBest2 was
      expressed on the cilia of OSNs, the site of olfactory transduction, and
      colocalized with the main CNGA2 channel subunit. Electrophysiological properties
      of Ca-activated Cl currents from native channels in dendritic knob/cilia of mouse
      OSNs were compared with those induced by the expression of mBest2 in HEK-293
      cells. We found the same anion permeability sequence, small estimated single
      channel conductances, a Ca sensitivity difference of one order of magnitude, and
      the same side-specific blockage of the two Cl channel blockers commonly used to
      inhibit the odorant-induced Ca-activated Cl current in OSNs, niflumic acid, and 4
      acetamido-4'-isothiocyanato-stilben-2,2'-disulfonate (SITS). Therefore, our data
      suggest that mBest2 is a good candidate for being a molecular component of the
      olfactory Ca-activated Cl channel.

PMID- 16912114
TI  - Space and stochasticity in population dynamics.
AB  - Organisms interact with each other mostly over local scales, so the local density
      experienced by an individual is of greater importance than the mean density in a
      population. This simple observation poses a tremendous challenge to theoretical
      ecology, and because nonlinear stochastic and spatial models cannot be solved
      exactly, much effort has been spent in seeking effective approximations. Several
      authors have observed that spatial population systems behave like deterministic
      nonspatial systems if dispersal averages the dynamics over a sufficiently large
      scale. We exploit this fact to develop an exact series expansion, which allows
      one to derive approximations of stochastic individual-based models without
      resorting to heuristic assumptions. Our approach makes it possible to calculate
      the corrections to mean-field models in the limit where the interaction range is
      large, and it provides insight into the performance of moment closure methods.
      With this approach, we demonstrate how the buildup of spatiotemporal correlations
      slows down the spread of an invasion, prolongs time lags associated with
      extinction debt, and leads to locally oscillating but globally stable coexistence
      of a host and a parasite.

PMID- 16912115
TI  - Severe acute respiratory syndrome coronavirus nsp1 protein suppresses host gene
      expression by promoting host mRNA degradation.
AB  - Severe acute respiratory syndrome (SARS) coronavirus (SCoV) causes a recently
      emerged human disease associated with pneumonia. The 5' end two-thirds of the
      single-stranded positive-sense viral genomic RNA, gene 1, encodes 16 mature
      proteins. Expression of nsp1, the most N-terminal gene 1 protein, prevented
      Sendai virus-induced endogenous IFN-beta mRNA accumulation without inhibiting
      dimerization of IFN regulatory factor 3, a protein that is essential for
      activation of the IFN-beta promoter. Furthermore, nsp1 expression promoted
      degradation of expressed RNA transcripts and host endogenous mRNAs, leading to a
      strong host protein synthesis inhibition. SCoV replication also promoted
      degradation of expressed RNA transcripts and host mRNAs, suggesting that nsp1
      exerted its mRNA destabilization function in infected cells. In contrast to nsp1
      induced mRNA destablization, no degradation of the 28S and 18S rRNAs occurred in
      either nsp1-expressing cells or SCoV-infected cells. These data suggested that,
      in infected cells, nsp1 promotes host mRNA degradation and thereby suppresses
      host gene expression, including proteins involved in host innate immune
      functions. SCoV nsp1-mediated promotion of host mRNA degradation may play an
      important role in SCoV pathogenesis.

PMID- 16912116
TI  - How to become a uropathogen: comparative genomic analysis of extraintestinal
      pathogenic Escherichia coli strains.
AB  - Uropathogenic Escherichia coli (UPEC) strain 536 (O6:K15:H31) is one of the model
      organisms of extraintestinal pathogenic E. coli (ExPEC). To analyze this strain's
      genetic basis of urovirulence, we sequenced the entire genome and compared the
      data with the genome sequence of UPEC strain CFT073 (O6:K2:H1) and to the
      available genomes of nonpathogenic E. coli strain MG1655 (K-12) and
      enterohemorrhagic E. coli. The genome of strain 536 is approximately 292 kb
      smaller than that of strain CFT073. Genomic differences between both UPEC are
      mainly restricted to large pathogenicity islands, parts of which are unique to
      strain 536 or CFT073. Genome comparison underlines that repeated insertions and
      deletions in certain parts of the genome contribute to genome evolution.
      Furthermore, 427 and 432 genes are only present in strain 536 or in both UPEC,
      respectively. The majority of the latter genes is encoded within smaller
      horizontally acquired DNA regions scattered all over the genome. Several of these
      genes are involved in increasing the pathogens' fitness and adaptability.
      Analysis of virulence-associated traits expressed in the two UPEC O6 strains,
      together with genome comparison, demonstrate the marked genetic and phenotypic
      variability among UPEC. The ability to accumulate and express a variety of
      virulence-associated genes distinguishes ExPEC from many commensals and forms the
      basis for the individual virulence potential of ExPEC. Accordingly, instead of a
      common virulence mechanism, different ways exist among ExPEC to cause disease.

PMID- 16912117
TI  - Two-dimensional electronic spectroscopy of the B800-B820 light-harvesting
      complex.
AB  - Emerging nonlinear optical spectroscopies enable deeper insight into the
      intricate world of interactions and dynamics of complex molecular systems. 2D
      electronic spectroscopy appears to be especially well suited for studying
      multichromophoric complexes such as light-harvesting complexes of photosynthetic
      organisms as it allows direct observation of couplings between the pigments and
      charts dynamics of energy flow on a 2D frequency map. Here, we demonstrate that a
      single 2D experiment combined with self-consistent theoretical modeling can
      determine spectroscopic parameters dictating excitation energy dynamics in the
      bacterial B800-B820 light-harvesting complex, which contains 27
      bacteriochlorophyll molecules. Ultrafast sub-50-fs dynamics dominated by coherent
      intraband processes and population transfer dynamics on a picosecond time scale
      were measured and modeled with one consistent set of parameters. Theoretical 2D
      spectra were calculated by using a Frenkel exciton model and modified
      Forster/Redfield theory for the calculation of dynamics. They match the main
      features of experimental spectra at all population times well, implying that the
      energy level structure and transition dipole strengths are modeled correctly in
      addition to the energy transfer dynamics of the system.

PMID- 16912118
TI  - SNF1-related kinases allow plants to tolerate herbivory by allocating carbon to
      roots.
AB  - Herbivore attack elicits costly defenses that are known to decrease plant fitness
      by using resources that are normally slated for growth and reproduction.
      Additionally, plants have evolved mechanisms for tolerating attack, which are not
      understood on a molecular level. Using 11C-photosynthate labeling as well as
      sugar and enzyme measurements, we found rapid changes in sink-source relations in
      the annual Nicotiana attenuata after simulated herbivore attacks, which increased
      the allocation of sugars to roots. This herbivore-induced response is regulated
      by the beta-subunit of an SnRK1 (SNF1-related kinase) protein kinase, GAL83,
      transcripts of which are rapidly down-regulated in source leaves after herbivore
      attack and, when silenced, increase assimilate transport to roots. This C
      diversion response is activated by herbivore-specific elicitors and is
      independent of jasmonate signaling, which regulates most of the plant's defense
      responses. Herbivore attack during early stages of development increases root
      reserves, which, in turn, delays senescence and prolongs flowering. That attacked
      GAL83-silenced plants use their enhanced root reserves to prolong reproduction
      demonstrates that SnRK1 alters resource allocation so that plants better tolerate
      herbivory. This tolerance mechanism complements the likely defensive value of
      diverting resources to a less vulnerable location within the plant.

PMID- 16912119
TI  - Enhancing the potential of quality improvement organizations to improve quality
      of care.

PMID- 16912120
TI  - Differences in the apparent metabolic clearance rate of testosterone in young and
      older men with gonadotropin suppression receiving graded doses of testosterone.
AB  - BACKGROUND: Recently we found that testosterone levels are higher in older men
      than young men receiving exogenous testosterone. We hypothesized that older men
      have lower apparent testosterone metabolic clearance rates (aMCR-T) that
      contribute to higher testosterone levels. OBJECTIVE: The objective of the study
      was to compare aMCR-T in older and young men and identify predictors of aMCR-T.
      METHODS: Sixty-one younger (19-35 yr) and 60 older (59-75 yr) men were given a
      monthly GnRH agonist and weekly testosterone enanthate (TE) (25, 50, 125, 300, or
      600 mg) for 5 months. Estimated aMCR-T was calculated from the amount of TE
      delivered weekly and trough serum testosterone concentrations, corrected for real
      time absorption kinetics from the im testosterone depot. RESULTS: Older men had
      lower total (316 +/- 13 vs. 585 +/- 26 ng/dl, P < 0.00001) and free testosterone
      (4 +/- 0.1 vs. 6 +/- 0.3 ng/dl, P < 0.00001) and higher SHBG (52 +/- 3 vs. 33 +/-
      2 nmol/liter, P < 0.00001) than younger men at baseline. Total and free
      testosterones increased with TE dose and were higher in older men than young men
      in the 125-, 300-, and 600-mg dose groups. aMCR-T was lower in older men than
      young men (1390 +/- 69 vs. 1821 +/- 102 liter/d, P = 0.006). aMCR-T correlated
      negatively with age (P = 0.0007), SHBG (P = 0.046), and total testosterone during
      treatment (P = 0.02) and percent body fat at baseline (P = 0.01) and during
      treatment (P = 0.004). aMCR-T correlated positively with lean body mass at
      baseline (P = 0.03) and during treatment (P = 0.01). In multiple regression
      models, significant predictors of aMCR-T included lean body mass (P = 0.008),
      percent fat mass (P = 0.009), and SHBG (P = 0.001). CONCLUSIONS: Higher
      testosterone levels in older men receiving TE were associated with an age-related
      decrease in apparent testosterone metabolic clearance rates. Body composition and
      SHBG were significant predictors of aMCR-T.

PMID- 16912121
TI  - Serum insulin-like growth factor-I (IGF-I) and growth in children born after
      assisted reproduction.
AB  - CONTEXT: Concern has been raised about the safety of assisted reproduction
      techniques for the offspring. OBJECTIVES: The objective of the study was to
      investigate postnatal growth and growth factors in children born after intra
      cytoplasmatic sperm injection (ICSI) and in vitro fertilization (IVF). DESIGN:
      The study had two cohorts: a population-based longitudinal infant cohort 0-36
      months [236 ICSI, 173 IVF, 1530 naturally conceived (NC)], and a cross-sectional
      child cohort at 5 yr (68 ICSI, 67 IVF, 70 NC). INTERVENTION: Anthropometrical
      measurements were made at birth, 3, 18, 36 (infant cohort), and 60 months (child
      cohort), and blood samples were collected at 3 or 60 months. MAIN OUTCOME
      MEASURES: Serum IGF-I, IGFBP-3, height, weight, head and abdominal circumference,
      body mass index, and fat folds were the main outcome measures. RESULTS:
      Anthropometrical measurements showed no significant differences between ICSI and
      IVF children and controls in either cohort. However, singleton ICSI girls [3.4
      (0.6) kg, P = 0.008] had a slightly lower birth weight than IVF [3.5 (0.5) kg]
      and NC girls [3.5 (0.5) kg]. Birth weights of singleton boys [3.6 (0.5) kg], twin
      boys [2.6 (0.6) kg], and twin girls [2.4 (0.5) kg] did not differ between types
      of conception. In the infant cohort in 3-month-old singletons, serum IGF-I was
      lower in ICSI [78 (26) ng/ml] than NC boys [94 (27) ng/ml, P < 0.001] and IVF [74
      (34) ng/ml], compared with NC girls [93 (43) ng/ml, P = 0.011]. ICSI children
      were also smaller than their target height (sd score) at 3 yr of age [mean -0.91
      (1.2)], compared with NC children [-0.61 (0.9), P = 0.033]. In the child cohort,
      target height attainment (sd score) and growth factors did not differ among the
      three groups. CONCLUSIONS: The overall growth pattern of ICSI and IVF children in
      both cohorts was normal. Our findings of subtle differences in target height
      attainment and serum IGF-I levels between infants born after assisted
      reproduction techniques and controls may not be clinically significant. However,
      these observations indicate that further systematic follow-up of growth and
      puberty in these children is needed.

PMID- 16912122
TI  - Autoimmune thyroiditis and exposure to iodine 131 in the Ukrainian cohort study
      of thyroid cancer and other thyroid diseases after the Chornobyl accident:
      results from the first screening cycle (1998-2000).
AB  - CONTEXT: Due to the Chornobyl accident, millions were exposed to radioactive
      isotopes of iodine and some received appreciable iodine 131 (131I) doses. A
      subsequent increase in thyroid cancer has been largely attributed to this
      exposure, but evidence concerning autoimmune thyroiditis (AIT) remains
      inconclusive. OBJECTIVE: The objective of the study was to quantify risk of AIT
      after 131I exposure. DESIGN/SETTING/PARTICIPANTS: Baseline data were collected
      from the first screening cycle (1998-2000) of a large cohort of radiation-exposed
      individuals (n = 12,240), residents of contaminated, iodine-deficient territories
      of Ukraine. Study individuals were under the age of 18 yr on April 26, 1986, and
      had thyroid radioactivity measurements made shortly after the accident. OUTCOMES:
      AIT was defined a priori based on various combinations of elevated antibodies to
      thyroid peroxidase (ATPO), TSH, and clinical findings; elevated ATPO were
      considered to be an indicator of thyroid autoimmunity. RESULTS: No significant
      association was found between 131I thyroid dose estimates and AIT, but prevalence
      of elevated ATPO demonstrated a modest, significant association with 131I that
      was well described by several concave models. This relationship was apparent in
      individuals with moderately elevated ATPO and euthyroid, thyroid disease-free
      individuals. CONCLUSIONS: Twelve to 14 yr after the Chornobyl accident, no
      radiation-related increase in prevalence of AIT was found in a large cohort
      study, the first in which 131I thyroid doses were estimated using individual
      radioactivity measurements. However, a dose-response relationship with ATPO
      prevalence raises the possibility that clinically important changes may occur
      over time. Thus, further follow-up and analysis of prospective data in this
      cohort are necessary.

PMID- 16912123
TI  - Cathepsin K in adipocyte differentiation and its potential role in the
      pathogenesis of obesity.
AB  - CONTEXT: The alteration of protein expression in white adipose tissue (WAT) may
      contribute to the pathogenesis of obesity. OBJECTIVE: The aim of the present
      study was to uncover proteins differentially expressed in the WAT of
      overweight/obese subjects and study the role of the identified proteins in
      adipocyte differentiation. DESIGN AND SETTING: Two-dimensional electrophoresis
      and matrix-assisted laser desorption ionization-time of flight-mass spectrometry
      were used to identify proteins differentially expressed in WAT between
      obese/overweight and control groups. Cathepsin K (CTSK), one of the proteins
      identified by the above methods, was highlighted to assess its effects on
      adipocyte differentiation through 3T3-L1 cell line. RESULTS: Human visceral
      adipose tissue of overweight/obese subjects displayed a differential protein
      expression profile, compared with that of normal-weight controls. CTSK was up
      regulated in the WAT of overweight/obese subjects, and it had a significant
      positive correlation with body mass index. In vitro study showed that CTSK
      expression and its enzyme activity gradually increased in the process of
      adipocyte differentiation. Moreover, E-64, an inhibitor of CTSK, could prevent
      adipocyte differentiation in a dose-dependent manner, which was characterized by
      the absence of triglyceride accumulation and glycerol contents. CONCLUSIONS:
      CTSK, a cysteine protease involved in extracellular matrix remodeling, could be
      one of the determinants of adipocyte differentiation. CTSK may be involved in the
      pathogenesis of obesity by promoting adipocyte differentiation.

PMID- 16912124
TI  - Extensive clinical experience: nonclassical 21-hydroxylase deficiency.
AB  - CONTEXT: Nonclassical congenital adrenal hyperplasia (CAH) owing to steroid 21
      hydroxylase deficiency (NC21OHD) is the most frequent of all autosomal recessive
      genetic diseases, occurring in one in 100 persons in the heterogeneous New York
      City population. NC21OHD occurs with increased frequency in certain ethnic
      groups, such as Ashkenazi Jews, in whom one in 27 express the disease. NC21OHD is
      underdiagnosed in both male and female patients with hyperandrogenic symptoms
      because hormonal abnormalities in NC21OHD are only mild to moderate, not severe
      as in the classical form of CAH. Unlike classical CAH, NC21OHD is not associated
      with ambiguous genitalia of the newborn female. MAIN OUTCOME MEASURES: The
      hyperandrogenic symptoms include advanced bone age, early pubic hair, precocious
      puberty, tall stature, and early arrest of growth in children; infertility,
      cystic acne, and short stature in both adult males and females; hirsutism,
      frontal balding, polycystic ovaries, and irregular menstrual periods in females;
      and testicular adrenal rest tissue in males. CONCLUSIONS: The signs and symptoms
      of hyperandrogenism are reversed with dexamethasone treatment.

PMID- 16912125
TI  - Midlife plasma insulin-like growth factor I and cognitive function in older men.
AB  - CONTEXT: Emerging biological and epidemiological evidence suggests possible
      benefits of higher IGF-I levels in cognitive aging. OBJECTIVE: The objective of
      the study was to examine the relation of midlife plasma IGF-I levels to late-life
      cognition. DESIGN, SETTING, AND PARTICIPANTS: We conducted a secondary analysis
      from the Physicians' Health Study II, a prospective cohort of U.S. male
      physicians. Participants provided blood samples from 1982 to 1984 (mean age 57
      yr). Using stored samples, we measured free IGF-I in 376 men and total IGF-I and
      IGF binding protein-3 in 460 men. Starting in 2001, we administered telephone
      based tests of general cognition [the Telephone Interview of Cognitive Status
      (TICS)], verbal memory, and category fluency. We estimated multivariable-adjusted
      mean differences in cognitive performance across levels of free IGF-I and IGF-I
      to IGF binding protein-3 molar ratio. MAIN OUTCOME MEASURES: Global score
      (averaging performance across all individual cognitive tests), the TICS, and a
      verbal memory score were measured. RESULTS: Each sd increment in free IGF-I was
      associated with a multivariable-adjusted increase of 0.08 U (P = 0.02) on the
      global score. This mean difference was equivalent to that observed between men 2
      yr apart in age: i.e. each sd increase in free IGF-I appeared cognitively
      equivalent to staying 2 yr younger. No significant mean differences in TICS
      scores were observed across free IGF-I levels. For verbal memory, each sd
      increment in free IGF-I was associated with an adjusted mean difference of 0.08 U
      (P = 0.03). Results appeared consistent for the molar ratio but were not
      statistically significant. CONCLUSION: Higher midlife free IGF-I may be
      associated with better late-life cognition.

PMID- 16912126
TI  - Effects of chronic osteoarthritis pain on neuroendocrine function in men.
AB  - CONTEXT: Chronic pain has been associated with elevated cortisol, reduced LH and
      testosterone (T), and/or augmented circulating or excreted catecholamines. Most
      endocrine studies have been conducted in patients in whom the potentially
      confounding effects of depression, inflammatory disease, or coexistent medication
      use have not been controlled. OBJECTIVE: The objective of the study was to test
      the hypothesis that chronic pain activates ACTH-cortisol and suppresses LH-T.
      DESIGN AND SETTING: This was a case control study conducted at a clinical
      research center. PARTICIPANTS: Participants included 16 opioid-naive men with
      chronic osteoarthritis pain, aged 35-65 yr with body mass index 20-30 kg/m2, and
      12 healthy, opioid- and pain-free men of similar ages and body mass indexes.
      METHODS: We compared circulating concentrations of ACTH, cortisol, LH, and T
      derived from every 20-min blood sampling (2000-0800 h), and 24-h urinary
      excretion of cortisol, epinephrine, norepinephrine, and dopamine. RESULTS: There
      were no significant differences in mean or integrated concentrations of ACTH,
      cortisol, LH, or T, or in the corresponding approximate entropy scores in
      osteoarthritis patients, compared with control subjects. The 0800-h serum LH
      concentrations were elevated in patients vs. controls (6.42 +/- 1.65 vs. 3.99 +/-
      1.54 IU/liter, mean +/- sd, P = 0.02), whereas there were no significant group
      differences in total or free T, SHBG, cortisol binding globulin,
      dehydroepiandrosterone sulfate, or urinary cortisol and catecholamines.
      CONCLUSIONS: These data suggest that neuroendocrine function is not significantly
      altered in otherwise healthy men with chronic musculoskeletal pain and that prior
      reports of such hormonal abnormalities may have resulted from the confounding
      effects of coexistent illness or medication use.

PMID- 16912127
TI  - Alanine aminotransferase levels and fatty liver in childhood obesity:
      associations with insulin resistance, adiponectin, and visceral fat.
AB  - BACKGROUND: Concurrent with the rise in obesity, nonalcoholic fatty liver disease
      is recognized as the leading cause of serum aminotransferase elevations in obese
      youth. Nevertheless, the complete metabolic phenotype associated with
      abnormalities in biomarkers of liver injury and intrahepatic fat accumulation
      remains to be established. METHODS: In a multiethnic cohort of 392 obese
      adolescents, alanine aminotransferase (ALT) levels were related with parameters
      of insulin sensitivity, glucose, and lipid metabolism as well as adipocytokines
      and biomarkers of inflammation. A subset of 72 adolescents had determination of
      abdominal fat partitioning and intrahepatic fat accumulation using magnetic
      resonance imaging. FINDINGS: Elevated ALT (> 35 U/liter) was found in 14% of
      adolescents, with a predominance of male gender and white/Hispanic
      race/ethnicity. After adjusting for potential confounders, rising ALT was
      associated with reduced insulin sensitivity and glucose tolerance as well as
      rising free fatty acids and triglycerides. Worsening of glucose and lipid
      metabolism was already evident as ALT levels rose into the upper half of the
      normal range (18-35 U/liter). When hepatic fat fraction was assessed using fast
      magnetic resonance imaging, 32% of subjects had an increased hepatic fat
      fraction, which was associated with decreased insulin sensitivity and
      adiponectin, and increased triglycerides, visceral fat, and deep to superficial
      sc fat ratio. The prevalence of the metabolic syndrome was significantly greater
      in those with fatty liver. INTERPRETATION: Deterioration in glucose and lipid
      metabolism is associated even with modest ALT elevations. Hepatic fat
      accumulation in childhood obesity is strongly associated with the triad of
      insulin resistance, increased visceral fat, and hypoadiponectinemia. Hence,
      hepatic steatosis may be a core feature of the metabolic syndrome.

PMID- 16912128
TI  - Effect of single oral doses of sitagliptin, a dipeptidyl peptidase-4 inhibitor,
      on incretin and plasma glucose levels after an oral glucose tolerance test in
      patients with type 2 diabetes.
AB  - CONTEXT: In response to a meal, glucagon-like peptide-1 (GLP-1) and glucose
      dependent insulinotropic peptide (GIP) are released and modulate glycemic
      control. Normally these incretins are rapidly degraded by dipeptidyl peptidase-4
      (DPP-4). DPP-4 inhibitors are a novel class of oral antihyperglycemic agents in
      development for the treatment of type 2 diabetes. The degree of DPP-4 inhibition
      and the level of active incretin augmentation required for glucose lowering
      efficacy after an oral glucose tolerance test (OGTT) were evaluated. OBJECTIVE:
      The objective of the study was to examine the pharmacodynamics, pharmacokinetics,
      and tolerability of sitagliptin. DESIGN: This was a randomized, double-blind,
      placebo-controlled, three-period, single-dose crossover study. SETTING: The study
      was conducted at six investigational sites. PATIENTS: The study population
      consisted of 58 patients with type 2 diabetes who were not on antihyperglycemic
      agents. INTERVENTIONS: Interventions included sitagliptin 25 mg, sitagliptin 200
      mg, or placebo. MAIN OUTCOME MEASURES: Measurements included plasma DPP-4
      activity; post-OGTT glucose excursion; active and total incretin GIP levels;
      insulin, C-peptide, and glucagon concentrations; and sitagliptin
      pharmacokinetics. RESULTS: Sitagliptin dose-dependently inhibited plasma DPP-4
      activity over 24 h, enhanced active GLP-1 and GIP levels, increased insulin/C
      peptide, decreased glucagon, and reduced glycemic excursion after OGTTs
      administered at 2 and 24 h after single oral 25- or 200-mg doses of sitagliptin.
      Sitagliptin was generally well tolerated, with no hypoglycemic events.
      CONCLUSIONS: In this study in patients with type 2 diabetes, near maximal glucose
      lowering efficacy of sitagliptin after single oral doses was associated with
      inhibition of plasma DPP-4 activity of 80% or greater, corresponding to a plasma
      sitagliptin concentration of 100 nm or greater, and an augmentation of active GLP
      1 and GIP levels of 2-fold or higher after an OGTT.

PMID- 16912129
TI  - Impact of combined estradiol and norethindrone therapy on visuospatial working
      memory assessed by functional magnetic resonance imaging.
AB  - CONTEXT: Hormones regulate neuronal function in brain regions critical to
      cognition; however, the cognitive effects of postmenopausal hormone therapy are
      controversial. OBJECTIVE: The goal was to evaluate the effect of postmenopausal
      hormone therapy on neural circuitry involved in spatial working memory. DESIGN: A
      randomized, double-blind, placebo-controlled crossover study was performed.
      SETTING: The study was performed in a tertiary care university medical center.
      PARTICIPANTS: Ten healthy postmenopausal women of average age 56.9 yr were
      recruited. INTERVENTIONS: Volunteers were randomized to the order they received
      hormone therapy (5 microg ethinyl estradiol and 1 mg norethindrone acetate).
      Subjects received hormone therapy or placebo for 4 wk, followed by a 1-month
      washout period with no medications, and then received the other treatment for 4
      wk. At the end of each 4-wk treatment period, a functional magnetic resonance
      imaging study was performed using a nonverbal (spatial) working memory task, the
      Visual Delayed Matching to Sample task. MAIN OUTCOME MEASURE: The effects of
      hormone therapy on brain activation patterns were compared with placebo. RESULTS:
      Compared with the placebo condition, hormone therapy was associated with a more
      pronounced activation in the prefrontal cortex (BA 44 and 45), bilaterally (P <
      0.001). CONCLUSIONS: Hormone therapy was associated with more effective
      activation of a brain region critical in primary visual working memory tasks. The
      data suggest a functional plasticity of memory systems in older women that can be
      altered by hormones.

PMID- 16912130
TI  - Identification of three novel mutations in the GATA3 gene responsible for
      familial hypoparathyroidism and deafness in the Chinese population.
AB  - BACKGROUND: Familial hypoparathyroidism may be caused by mutations of several
      genes. The CaSR and GATA3 genes are the two candidates most commonly responsible
      for this condition. OBJECTIVES: We collected five unrelated families with
      familial hypoparathyroidism and examined their CaSR and GATA3 genes. METHODS:
      Blood samples from these five families and 50 ethnically matched unrelated
      controls were acquired. Biochemistry screening and formal audiogram were
      performed to evaluate the affected individuals. All the exons and exon-intron
      boundaries of the GATA3 and CaSR genes were sequenced. RESULTS: We identified
      three novel mutations in the GATA3 gene responsible for familial
      hypoparathyroidism and deafness: 1) a frameshift deletion occurring in codon 160
      (478delG) was hypothesized to disrupt dual zinc fingers as well as one
      transactivating domain; 2) a donor splice site mutation at exon 4/intron 4
      boundary (IVS4 + 2 T to GCTTACTTCCC) was predicted to lead to truncated GATA3
      proteins that lack both N- and C-terminal zinc-containing fingers; and 3) a
      missense mutation R353S was predicted to disrupt the helical turn and thus
      changed the angle between the C-terminal zinc finger and the adjacent C-terminal
      tail. Except for a previously described polymorphism, G990R, we did not find any
      genetic variants in the CaSR gene. CONCLUSIONS: This is the first article
      presenting mutations of the GATA3 gene responsible for familial
      hypoparathyroidism and deafness in the Chinese population. Our results expand the
      spectrum of mutations and report the first splice donor site mutation of the
      GATA3 gene. In contrast, we do not find causal sequence variants of the CaSR gene
      from our collection of familial hypoparathyroidism.

PMID- 16912131
TI  - Longitudinal changes in insulin-like growth factor-I, insulin sensitivity, and
      secretion from birth to age three years in small-for-gestational-age children.
AB  - INTRODUCTION: Insulin resistance (IR) develops as early as age 1 to 3 yr in small
      for gestational age (SGA) infants who show rapid catch-up postnatal weight gain.
      In contrast, greater insulin secretion is related to infancy height gains. We
      hypothesized that IGF-I levels could be differentially related to gains in length
      and weight and also differentially related to IR and insulin secretion. METHODS:
      In a prospective study of 50 SGA (birth weight < 5th percentile) and 14 normal
      birth weight [appropriate for gestational age (AGA)] newborns, we measured serum
      IGF-I levels at birth, 1 yr, and 3 yr. IR (by homeostasis model assessment) and
      insulin secretion (by short iv glucose tolerance test) were also measured at 1 yr
      and 3 yr. RESULTS: SGA infants had similar mean length and weight at 3 yr
      compared with AGA infants. SGA infants had lower IGF-I levels at birth (P <
      0.0001), but conversely they had higher IGF-I levels at 3 yr (P = 0.003) than AGA
      infants. Within the SGA group, at 1 yr IGF-I was associated with length gain from
      birth and insulin secretion (P < 0.0001); in contrast at 3 yr IGF-I was
      positively related to weight, body mass index, and IR. CONCLUSIONS: IGF-I levels
      increased rapidly from birth in SGA, but not AGA children. During the key first
      year growth period, IGF-I levels were related to beta-cell function and
      longitudinal growth. In contrast, by 3 yr, when catch-up growth was completed,
      IGF-I levels were related to body mass index and IR, and these higher IGF-I
      levels in SGA infants might indicate the presence of relative IGF-I resistance.

PMID- 16912132
TI  - Adiponectin and mortality in patients undergoing coronary angiography.
AB  - CONTEXT: The adipokine adiponectin has been suggested to protect against coronary
      artery disease (CAD). However, studies addressing the association between
      adiponectin and mortality are sparse. OBJECTIVE: The objective of the study was
      to elucidate the relationship between adiponectin and mortality. DESIGN, SETTING,
      AND PARTICIPANTS: Adiponectin was determined in 2473 persons with and 673 persons
      without angiographic CAD. During a mean follow-up period of 5.45 yr, 427 persons
      with CAD and 55 persons without CAD died. MAIN OUTCOME MEASURE: Hazard ratios for
      mortality according to adiponectin levels were measured. RESULTS: Adiponectin was
      positively related to female gender, age, low-density lipoprotein cholesterol,
      high-density lipoprotein cholesterol, homocysteine, and N-terminal pro-B-type
      natriuretic peptide. It was inversely related to glomerular filtration rate, body
      mass index, and triglycerides and was low in diabetes mellitus and CAD. An
      increase of 1 sd in adiponectin was associated with unadjusted and fully adjusted
      hazard ratios for death from any cause of 1.31 [95% confidence interval (CI) 1.20
      1.42] and 1.22 (95% CI 1.12-1.34), and for death from cardiovascular causes of
      1.32 (95% CI 1.19-1.45) and 1.23 (95% CI 1.11-1.37), respectively. In
      angiographic CAD, stable CAD, and unstable CAD, the predictive value of
      adiponectin was similar to that in the entire cohort, but it did not attain
      statistical significance in persons without angiographic CAD. Adiponectin was
      also positively related to the risk of death from noncardiovascular causes.
      CONCLUSIONS: Despite the common view about adiponectin as a protective molecule
      in cardiovascular disease, high adiponectin independently predicts all-cause,
      cardiovascular, and noncardiovascular mortality in individuals with CAD.

PMID- 16912133
TI  - Divergent phenotype of two siblings human leukocyte antigen identical, affected
      by nonclassical and classical congenital adrenal hyperplasia caused by 21
      hydroxylase deficiency.
AB  - CONTEXT: Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive
      disorders most often caused by enzyme 21-hydroxylase deficiency. Most mutations
      causing enzymatic deficiency are generated by recombinations between the active
      gene CYP21 and the pseudogene CYP21P. Only 1-2% of affected alleles result from
      spontaneous mutations. The phenotype of CAH varies greatly, usually classified as
      classical or nonclassical, depending on variable degree in 21-hydroxylase
      activity. Here we report a divergent phenotype of two human leukocyte antigen
      identical siblings, affected by nonclassical and classical CAH caused by 21
      hydroxylase deficiency due to different genotype. PATIENTS AND METHODS: Using
      direct sequencing method and Southern blot, we studied two children (one male and
      one female), affected, respectively, by nonclassical and classical CAH and their
      parents. RESULTS: The mother was heterozygous for the Q318X mutation, and the
      father was heterozygous for the V281L mutation. The brother was a compound
      heterozygote for the mutations V281L and Q318X, whereas the proband was compound
      heterozygote for the Q318X mutation and a large conversion. The two children are
      human leukocyte antigen identical (A*02;B*14;DRB1*01/A*33;B*14;DRB1*03).
      CONCLUSIONS: Different phenotype of the proband is the result of compound
      heterozygosity for the maternal mutation Q318X and a de novo large conversion.

PMID- 16912134
TI  - Associations of early growth and adult adiposity with patterns of salivary
      cortisol in adulthood.
AB  - CONTEXT: Early growth and obesity are associated with adult chronic disease. A
      suspected mediator is the hypothalamic-pituitary-adrenal axis and cortisol
      regulation. Our prior hypothesis was that cortisol levels are affected by
      anthropometry at several life stages. OBJECTIVE: The objective of the study was
      to assess whether prenatal and postnatal growth and adiposity are associated with
      adult cortisol levels, and whether early growth and adiposity are related to
      later cortisol through adult body size. DESIGN: Weight, head circumference
      (birth), height, and body mass index (BMI) (7 yr); and height, BMI (33 yr), and
      waist-hip ratio (WHR) (45 yr) were measured in the 1958 British birth cohort.
      SETTING: All study subjects were born in England, Scotland, and Wales in 1 wk in
      March 1958. PARTICIPANTS: A total of 6,470 participants with salivary cortisol
      were gathered from 12,069 invitees (54%) at 45 yr. MAIN OUTCOME MEASURES: Two
      saliva samples on 1 d were collected: 45 min postwaking (t1) and 3 h later (t2).
      Three cortisol outcomes were measured: t1 level, area-under-curve, and abnormal
      t1-t2 pattern. RESULTS: WHR was associated with all cortisol measures: among men
      over the WHR range 0.81-1.05, t1 cortisol decreased by approximately 3
      nmol/liter, and the risk of an abnormal t1-t2 pattern increased by 77%; for
      women, over the WHR range 0.69-0.93, the risk of an abnormal t1-t2 pattern
      increased by 74%. For childhood measures, among males, increasing 7-yr BMI was
      associated with decreased t1 cortisol and increased risk of an abnormal t1-t2
      pattern. Poorer prenatal growth in women, and postnatal growth in both sexes, was
      associated with increasing area-under-curve. CONCLUSIONS: Smaller head
      circumference, shorter stature, lower BMI, and WHR are associated with higher
      cortisol levels.

PMID- 16912135
TI  - Potent inhibitory effects of type I interferons on human adrenocortical carcinoma
      cell growth.
AB  - CONTEXT: Adrenocortical carcinoma (ACC) is a rare tumor with a poor prognosis.
      Despite efforts to develop new therapeutic regimens for metastatic ACC, surgery
      remains the mainstay of treatment. Interferons are known to exert tumor
      suppressive effects in several types of human cancer. DESIGN: We evaluated the
      tumor-suppressive effects of type I interferons (IFN)-alpha2b and IFNbeta on the
      H295 and SW13 human ACC cell lines. RESULTS: As determined by quantitative RT-PCR
      analysis and immunocytochemistry, H295 and SW13 cells expressed the active type I
      IFN receptor (IFNAR) mRNA and protein (IFNAR-1 and IFNAR-2c subunits). Both
      IFNalpha2b and IFNbeta1a significantly inhibited ACC cell growth in a dose
      dependent manner, but the effect of IFNbeta1a (IC50 5 IU/ml, maximal inhibition
      96% in H295; IC50 18 IU/ml, maximal inhibition 85% in SW13) was significantly
      more potent, compared with that of IFNalpha2b (IC50 57 IU/ml, maximal inhibition
      35% in H295; IC50 221 IU/ml, maximal inhibition 60% in SW13). Whereas in H295
      cells both IFNs induced apoptosis and accumulation of the cells in S phase, the
      antitumor mechanism in SW13 cells involved cell cycle arrest only. Inhibitors of
      caspase-3, caspase-8, and caspase-9 counteracted the apoptosis-inducing effect by
      IFNbeta1a in H295 cells. In H295 cells, IFNbeta1a, but not IFNalpha2b, also
      strongly suppressed the IGF-II mRNA expression, an important growth factor and
      hallmark in ACC. CONCLUSIONS: IFNbeta1a is much more potent than IFNalpha2b to
      suppress ACC cell proliferation in vitro by induction of apoptosis and cell cycle
      arrest. Further studies are required to evaluate the potency of IFNbeta1a to
      inhibit tumor growth in vivo.

PMID- 16912137
TI  - High frequency of SDHB germline mutations in patients with malignant
      catecholamine-producing paragangliomas: implications for genetic testing.
AB  - CONTEXT: Adrenal and extraadrenal paragangliomas are tumors of chromaffin cells
      that are usually benign but that may also develop into malignant disease.
      Mutations of the gene for succinate dehydrogenase subunit B (SDHB) are associated
      with a high risk of malignancy, but establishing the precise contribution
      requires relatively large numbers of patients with well-defined malignancy.
      OBJECTIVE: We assessed the prevalence of SDHB mutations in a series of patients
      with malignant paraganglioma. DESIGN: SDHB mutation testing was carried out in 44
      consecutive patients with malignant paraganglioma. Clinical characteristics of
      patients with malignant disease due to SDHB mutations were compared with those
      without mutations. RESULTS: Pathogenic SDHB mutations were found in 13 of the 44
      patients (30%). Close to one third of patients had metastases originating from an
      adrenal primary tumor, compared with a little over two thirds from an
      extraadrenal tumor. Among the latter patients, the frequency of SDHB mutations
      was 48%. CONCLUSION: This study establishes that missense, nonsense, frameshift,
      and splice site mutations of the SDHB gene are associated with about half of all
      malignancies originating from extraadrenal paragangliomas. The high frequency of
      SDHB germline mutations among patients with malignant disease, particularly when
      originating from an extraadrenal paraganglioma, may justify a high priority for
      SDHB germline mutation testing in these patients.

PMID- 16912136
TI  - Influence of demographic factors and sport type on growth hormone-responsive
      markers in elite athletes.
AB  - CONTEXT: GH-responsive markers of the IGF system and of collagen turnover hold
      promise as the basis of a GH doping test. OBJECTIVE: The purpose of this study
      was to determine the influence of age, gender, body mass index (BMI), ethnicity,
      and sporting type on GH-responsive serum markers in a large cohort of elite
      athletes from different ethnic backgrounds. DESIGN: The study was designed as a
      cross-sectional study. PARTICIPANTS: A total of 1103 elite athletes (699 males,
      404 females), aged 22.2 +/- 5.2 yr, from 12 countries and 10 major sporting
      categories participated in this study. MAIN OUTCOME MEASURES: Serum IGF-I, IGF
      binding protein-3 (IGFBP-3), acid labile subunit (ALS), and collagen markers [N
      terminal propeptide of type I procollagen (PINP), C-terminal telopeptide of type
      I collagen (ICTP), N-terminal propeptide of type III procollagen (PIIINP)] were
      measured. RESULTS: There was a significant negative correlation (r = -0.14 to 
      0.58, P < 0.0005) between age and each of the GH-responsive markers. Serum IGF-I,
      IGFBP-3, and ALS were all lower (P < 0.05), whereas the collagen markers PINP,
      ICTP, and PIIINP were higher (P < 0.05) in men than in women. Multiple regression
      analysis indicated that age, gender, BMI, and ethnicity accounted for 23-54% of
      total between-subject variability of the markers. Age and gender cumulatively
      accounted for 91% of the attributable variation of IGF-I and more than 80% for
      PINP, ICTP, and PIIINP. Gender exerted the greatest effect on ALS (48%), and BMI
      accounted for less than 12% attributable variation for all markers. The influence
      of ethnicity was greatest for IGFBP-3 and ALS; however, for the other markers, it
      accounted for less than 6% attributable variation. Analysis of 995 athletes
      indicated that sporting type contributed 5-19% of attributable variation.
      CONCLUSIONS: Age and gender were major determinants of variability of GH
      responsive markers except for IGFBP-3 and ALS. Ethnicity is unlikely to confound
      the validity of a GH doping test based on IGF-I and these collagen markers.

PMID- 16912138
TI  - Effect on adult height of pubertal growth hormone retesting and withdrawal of
      therapy in patients with previously diagnosed growth hormone deficiency.
AB  - CONTEXT: GH replacement therapy in GH-deficient (GHD) patients is usually
      continued until adult height despite the fact that most of these subjects display
      a normal secretion when retested at the end of growth. Puberty is the most likely
      time for normalization of GH secretion. OBJECTIVES: The objectives of this study
      are to establish the characteristics and the percentage of the subjects with
      isolated GHD who normalized secretion at puberty and to compare their statural
      outcomes with those of the subjects with persistent deficiency treated also after
      retesting. DESIGN AND SETTING: This was a prospective, nonrandomized, open-label
      study conducted in a university research hospital. PATIENTS AND INTERVENTION:
      Sixty-nine subjects (40 male, 29 female) with a diagnosis before puberty of
      isolated GHD by means of arginine and l-dopa tests were reevaluated with the same
      tests after at least 2 yr of therapy and after puberty onset. If GH peak at
      retesting was more than 10 microg/liter, therapy was withdrawn. MAIN OUTCOME
      MEASURES: Percentage and characteristics of normalized subjects at retesting,
      outcome of treatment in the subjects treated or untreated to adult height, and
      factors predictive of growth outcome were measured. RESULTS: At retesting, 44
      subjects (63.7%) confirmed a GH peak less than 10 microg/liter (24 of 40 male and
      20 of 29 female). Apart from a less delayed bone age at diagnosis in females, the
      subjects with confirmed GHD were not different at diagnosis from the other group
      for height deficit at diagnosis, first year growth response to GH, age and height
      at puberty onset, height, and IGF-I at retesting. Mean adult height was 165.1 +/-
      4.5 cm in the male group treated until adult height vs. 164.0 +/- 3.4 cm in the
      group who suspended therapy at retesting. Mean adult height was 153.2 +/- 4.1 cm
      in the female group treated until adult height vs. 152.9 +/- 5.2 cm in the group
      that suspended therapy at retesting. As regards the parameters expressing the
      final outcome, the only difference was found in the mean increment adult height
      target height sd score in favor of the male group treated until adult height. In
      both sexes, therapy duration and GH levels at diagnosis and at retesting were
      unrelated to adult height parameters and to height increments during the period
      of observation. CONCLUSIONS: One third of our GHD subjects diagnosed before
      puberty presented a normal secretion at puberty. The withdrawal of GH therapy in
      these subjects after retesting was not associated with a catch down growth, and
      they obtained an adult height similar to those obtained by the GHD subjects
      treated until adult height. It seems convenient, in subjects with nonsevere GHD,
      to retest GH secretion at midpuberty and to withdraw treatment for the subjects
      that are no longer deficient.

PMID- 16912140
TI  - Nutrient intake, weight, and Leu7Pro polymorphism in prepro-neuropeptide Y in
      children.
AB  - CONTEXT: The important role of neuropeptide Y (NPY) in the regulation of food
      intake and energy balance has been firmly documented in rodents, but human data
      are sparse. The recently identified functional Leu7Pro polymorphism in the signal
      peptide region of the prepro-NPY is a useful tool for the investigation of the
      role of NPY in men. Pro7 substitution has been associated with the following:
      plasma NPY concentration, the risk factors of cardiovascular disease, birth
      weight of children, serum triglyceride concentration, and the function of
      vascular endothelium. OBJECTIVE: The objective of this study was to analyze the
      connection between Leu7Pro polymorphism and relative weight, nutrient intakes,
      and serum lipids in early childhood. We closely followed 647 healthy Finnish
      children participating in the Special Turku Risk Factor Intervention Project
      through their first 9 yr of life. RESULTS: Leu7Pro polymorphism showed no
      relation to intakes of energy, macronutrients, or the relative weight in either
      gender. However, Pro7 substitution was associated with serum triglyceride
      concentration in boys at the ages of 5, 7, and 9 yr. CONCLUSION: The functional
      Leu7Pro polymorphism is not likely to be involved in the regulation of adiposity
      or major nutrient preferences in childhood. In boys, the Pro7 variant may have
      impact on serum triglyceride concentration.

PMID- 16912139
TI  - Serum androgen levels in black, Hispanic, and white men.
AB  - CONTEXT: Racial/ethnic differences in androgen levels could account for
      differences in prostate cancer risk, body composition, and bone loss. OBJECTIVE:
      The objective of the study was to investigate racial/ethnic variations in
      testosterone, bioavailable testosterone, dihydrotestosterone (DHT), SHBG, and
      dehydroepiandrosterone sulfate (DHEAS) levels. DESIGN: The Boston Area Community
      Health (BACH) Survey was a multistage stratified cluster random sample,
      recruiting from 2002 to 2005. SETTING: The study was a community-based sample of
      Boston. PARTICIPANTS: Participants included black, Hispanic, or white
      individuals, aged 30-79 yr, competent to sign informed consent and literate in
      English/Spanish. Of 2301 men recruited, 1899 provided blood samples (538 black,
      651 Hispanic, 710 white). INTERVENTION: Intervention consisted of data obtained
      during in-person at-home interview, conducted by a bilingual
      phlebotomist/interviewer. MAIN OUTCOME MEASURE(S): Testosterone, bioavailable
      testosterone, DHT, DHT to testosterone ratio, SHBG, and DHEAS were measured.
      RESULTS: With or without adjustment for covariates, there were no significant
      differences in testosterone, bioavailable testosterone, or SHBG levels by
      race/ethnicity. DHEAS levels differed by race/ethnicity before covariate
      adjustment; after adjustment this difference was attenuated. Before adjustment,
      DHT and DHT to testosterone ratios did not significantly differ by racial/ethnic
      group. After adjustment, there was evidence of racial/ethnic differences in DHT
      (P = 0.047) and DHT to testosterone (P = 0.038) levels. Black men had higher DHT
      levels and DHT to testosterone ratios than white and Hispanic men. CONCLUSIONS:
      Because there are no racial/ethnic differences in testosterone levels, normative
      ranges need not be adjusted by race/ethnicity for androgen deficiency diagnosis
      for men aged 30-79 yr. Further investigation is needed to determine whether
      differences in DHT levels and DHT to testosterone ratio can help explain
      racial/ethnic variations in prostate cancer incidence, body composition, and bone
      mass.

PMID- 16912141
TI  - Doing and reporting educational research.

PMID- 16912143
TI  - Living history of physiology: Carl Gans.
AB  - In 2005, The American Physiological Society initiated The Living History of
      Physiology Project to recognize senior members who have made extraordinary
      contributions during their career to the advancement of the discipline and
      profession of physiology. Each Eminent Physiologist will be interviewed for
      archival purposes, and the video tape will be available from the American
      Physiological Society Headquarters. In addition, a biographical profile of the
      recipient will be published in Advances in Physiology Education.

PMID- 16912144
TI  - Passing on the legacy: teaching capillary filtration and developing presentation
      skills using classic papers.
AB  - Capillary filtration is a key area in the understanding of cardiovascular
      function and has both physiological and pathophysiological relevance in nearly
      every organ system. This article describes how classic papers in the Legacy
      collection of American Physiological Society publications can be used in a
      teaching symposium exploring the evidence supporting current concepts of
      capillary fluid exchange. Individual students are given papers to read, edit, and
      present to the class. The appropriate selection and sequencing of these papers
      allows the development of important physiological concepts to be tracked. A
      series of papers concerned with capillary filtration is suggested, and the
      contribution of each to the developing story is outlined. This approach allows
      students to develop critical and presentation skills and provides them with a
      case study of the scientific method as it is applied to physiology as well as
      establishing an appropriate knowledge base concerning the role of hydrostatic and
      oncotic forces in capillary fluid exchange. Relevant teaching points are explored
      further using questions based on a figure from one of the three classic papers
      used: "Microinjection studies of capillary permeability: II. The relationship
      between capillary pressure and the rate at which fluid passes through the walls
      of single capillaries," by E. M. Landis (Am J Physiol 82: 217-238, 1927).

PMID- 16912145
TI  - Teaching skeletal muscle adaptations to aerobic exercise using an American
      Physiological Society classic paper by Dr. Philip Gollnick and colleagues.
AB  - The use of primary research in the classroom enhances the critical thinking
      abilities of students. The present article describes a strategy for using the
      American Physiological Society classic paper "Enzyme activity and fiber
      composition in skeletal muscle of untrained and trained men" by Dr. Philip D.
      Gollnick and colleagues to enhance the students' ability to understand research,
      increase their knowledge of the adaptations to exercise, and learn computer
      skills in data analysis and presentation. By having students read, study, prepare
      graphs, and discuss the data from a classic paper, they gain an improved
      understanding of the factors that influence aerobic exercise ability. This study
      is especially useful for illuminating the exercise-specific differences in
      bioenergetic enzymes, muscle fiber type, and fitness characteristics that exist
      between untrained and trained individuals.

PMID- 16912146
TI  - International student exchange and the medical curriculum: evaluation of a
      medical sciences translational physiology course in Brazil.
AB  - The objective of the present study was to conduct a short-term international
      course on translational physiology for medical students from Wright State
      University and the University of Iowa. The goals were to 1) provide students with
      an exposure to the academic, cultural, and medical environments in Brazil; 2)
      promote awareness of the global medical community; and 3) provide an academic
      course focused on translational physiology. An evaluation of the students was
      conducted to determine whether such a short-term course might be useful in the
      medical curriculum. The 2-wk course was held in the summer of 2005 at the
      University of Sao Paulo School of Medicine in Ribeirao Preto, Brazil, for 23
      American students. The program included presentations of basic and clinical
      topics, meetings with medical students, and clinical presentations. The program
      finished with student attendance at a scientific meeting sponsored by the
      Brazilian Society of Hypertension. Student surveys evaluated issues related to
      perceived treatment, Brazilian medical school environment, culture and personal
      attributes, and career aspirations. The international Medical Sciences
      Translational Physiology course for medical students provided a brief, but
      intense, experience. It gave students a picture of the medical environment in
      Brazil and an appreciation for the differences and similarities in cultures. Most
      students reported that it was a positive experience that would be beneficial to
      their careers. In conclusion, a short-term international course provides an
      efficient means for medical students to experience aspects of global medical
      science.

PMID- 16912147
TI  - Redefining classroom instruction.
AB  - In this study, the role of the classroom instructor was redefined from a
      "lecturer" responsible for delivering the core curriculum to a "facilitator" at
      the center of an active learning environment. Web-based lectures were used to
      provide foundation content to students outside of the classroom, which made it
      possible to improve the quality of student-faculty contact time in the classroom.
      Students reported that this hybrid format of instruction afforded them a better
      understanding of the content, a higher probability of retaining the content, and
      the opportunity to spend more time thinking about the application of the content
      compared with more traditional lecture-based methods of instruction.

PMID- 16912148
TI  - Demonstration of the origin of ECG waves.

PMID- 16912150
TI  - A simple model illustrating the respiratory system's time constant concept.

PMID- 16912151
TI  - Hydrogen sulfide is an endogenous modulator of leukocyte-mediated inflammation.
AB  - Hydrogen sulfide (H2S) is increasingly recognized as an important signaling
      molecule in the cardiovascular and nervous systems. Recently, H2S donors were
      reported to induce neutrophil apoptosis and to suppress expression of some
      leukocyte and endothelial adhesion molecules. Using rats, we examined the
      possibility that H2S is an endogenous regulator of key inflammatory events at the
      leukocyte-endothelial interface. Via intravital microscopy, we observed that H2S
      donors (NaHS and Na2S) inhibited aspirin-induced leukocyte adherence in
      mesenteric venules (ED50 of 5.0 micromol/kg for Na2S), likely via activation of
      ATP-sensitive K+ (K(ATP)) channels. Inhibition of endogenous H2S synthesis
      elicited leukocyte adherence. Leukocyte infiltration in an air pouch model was
      also suppressed by H2S donors (NaHS, Lawesson's reagent, and N-acetylcysteine;
      ED50 of 42.7, 1.3, and 29.9 micromol/kg, respectively) and exacerbated by
      inhibition of endogenous H2S synthesis. Carrageenan-induced paw edema was
      suppressed by H2S donors (NaHS and Na2S; ED50s of 35 and 28 micromol/kg,
      respectively) to the same extent as by diclofenac and enhanced by an inhibitor of
      H2S synthesis. Suppression of edema formation by H2S donors was mimicked by a
      K(ATP) channel agonist and reversed by an antagonist of this channel. These
      results suggest that endogenous H2S is an important mediator of acute
      inflammation, acting at the leukocyte-endothelium interface. These findings have
      important implications for anti-inflammatory drug development.

PMID- 16912152
TI  - Sleep enhances IL-6 trans-signaling in humans.
AB  - Sleep is commonly considered to support immune defense. The underlying sleep
      immune interaction appears to rely critically on cytokines, like interleukin-6
      (IL-6), that combine effects on immune and neuronal functions. The IL-6 signal is
      conveyed in two ways: it stimulates a restricted group of (mostly immune) cells
      via membrane-bound IL-6 receptors (mIL-6R) by forming a complex with soluble IL
      6R (sIL-6R), and it stimulates (via membrane-bound gp130) a great variety of
      other cell types--a process termed trans-signaling. Focusing on the receptor side
      of IL-6 signaling, we examined the effect of sleep on sIL-6R plasma
      concentrations, mIL-6R expression, plasma sgp130, and numbers of IL-6-producing
      monocytes in healthy humans who were tested during a regular sleep-wake cycle and
      24 h of wakefulness while blood was sampled repeatedly. Sleep strongly enhanced
      concentrations of sIL-6R, exceeding wake levels by 70% at the end of sleep. This
      rise was due to an increase in the PC (proteolytic cleavage) rather than the DS
      (differentially spliced) variant of sIL-6R. Sleep did not affect IL-6-producing
      monocytes, mIL-6R density, or sgp130 concentrations. The selective increase in
      sIL-6R implicates an enhanced trans-signaling capacity whereby sleep distinctly
      widens the profile of IL-6 actions, enabling an integrated influence on brain and
      peripheral organs.

PMID- 16912153
TI  - Influence of the microenvironment on melanoma cell fate determination and
      phenotype.
AB  - Tumor cells communicate bidirectionally with the surrounding microenvironment,
      sending and receiving topographical and molecular cues that direct diverse
      cellular phenomena, including differentiation, growth, and invasion. The
      microenvironment has long been acknowledged as a facilitator of melanoma
      progression, and recent studies have illuminated tumor-associated factors,
      including hypoxia and the extracellular matrix, as important mediators of
      melanocyte transformation and transdifferentiation. Although these findings
      portray the microenvironment as a perilous obstacle to the successful treatment
      of advanced melanomas, it is important to note that certain molecular milieus may
      be capitalized on as potential treatment modalities. Indeed, our group and others
      have elucidated the unique ability of embryonic microenvironments to normalize
      aggressive melanoma cells toward a more benign melanocytic phenotype. The
      microenvironment therefore presents a novel target for the treatment and
      ultimately the prevention of melanoma progression and metastasis.

PMID- 16912154
TI  - Switching on chromosomal translocations.
AB  - Activation-induced deaminase initiates three different antibody diversification
      reactions: class switch recombination, somatic hypermutation (SHM), and gene
      conversion. We have shown that, in addition to antibody diversification,
      activation-induced deaminase can also initiate Burkitt's lymphoma-like c-myc/IgH
      translocations. However, distinct DNA damage- and oncogene-induced checkpoints
      operate in B cells to produce a normal intrachromosomal class switch
      recombination event or an aberrant interchromosomal fusion. These findings open
      the way to study the molecular pathways taking place at the early stages of
      malignant transformation.

PMID- 16912155
TI  - Stem cell-like glioma cells promote tumor angiogenesis through vascular
      endothelial growth factor.
AB  - Malignant gliomas are highly lethal cancers dependent on angiogenesis. Critical
      tumor subpopulations within gliomas share characteristics with neural stem cells.
      We examined the potential of stem cell-like glioma cells (SCLGC) to support tumor
      angiogenesis. SCLGC isolated from human glioblastoma biopsy specimens and
      xenografts potently generated tumors when implanted into the brains of
      immunocompromised mice, whereas non-SCLGC tumor cells isolated from only a few
      tumors formed secondary tumors when xenotransplanted. Tumors derived from SCLGC
      were morphologically distinguishable from non-SCLGC tumor populations by
      widespread tumor angiogenesis, necrosis, and hemorrhage. To determine a potential
      molecular mechanism for SCLGC in angiogenesis, we measured the expression of a
      panel of angiogenic factors secreted by SCLGC. In comparison with matched non
      SCLGC populations, SCLGC consistently secreted markedly elevated levels of
      vascular endothelial growth factor (VEGF), which were further induced by hypoxia.
      In an in vitro model of angiogenesis, SCLGC-conditioned medium significantly
      increased endothelial cell migration and tube formation compared with non-SCLGC
      tumor cell-conditioned medium. The proangiogenic effects of glioma SCLGC on
      endothelial cells were specifically abolished by the anti-VEGF neutralizing
      antibody bevacizumab, which is in clinical use for cancer therapy. Furthermore,
      bevacizumab displayed potent antiangiogenic efficacy in vivo and suppressed
      growth of xenografts derived from SCLGC but limited efficacy against xenografts
      derived from a matched non-SCLGC population. Together these data indicate that
      stem cell-like tumor cells can be a crucial source of key angiogenic factors in
      cancers and that targeting proangiogenic factors from stem cell-like tumor
      populations may be critical for patient therapy.

PMID- 16912156
TI  - GRP78 as a novel predictor of responsiveness to chemotherapy in breast cancer.
AB  - The discovery of predictive factors for chemoresistance is critical for improving
      adjuvant therapy for cancer patients. The 78-kDa glucose-regulated protein
      (GRP78), widely used as an indicator of the unfolded protein response (UPR), is
      induced in the tumor microenvironment. In vitro studies suggest that GRP78
      confers chemoresistance to topoisomerase inhibitors, such as Adriamycin
      (doxorubicin). Here, we report on a retrospective cohort study of 127 stage II
      and III breast cancer patients who were treated with Adriamycin-based
      chemotherapy. Archival tumor specimens were available for analysis and the
      relationship of GRP78 expression level to "time to recurrence" (TTR), used as a
      surrogate marker for drug resistance, was examined. Our data show that 67% of the
      study subjects expressed high level of GRP78 in their tumors before the
      initiation of chemotherapy and suggest an association between GRP78 positivity
      and shorter TTR [hazard ratio (HR), 1.78; P = 0.16]. Interestingly, subgroup
      analysis reveals that the HR for the GRP78-positive group increased significantly
      among patients who did not receive further taxane treatment (HR, 3.00; P = 0.022)
      and among mastectomy patients (HR, 3.33; P = 0.027). The HR was even stronger
      among mastectomy patients who did not receive further taxane treatment (HR, 4.82;
      P = 0.010). The use of GRP78 as a predictor for chemoresponsiveness and the
      potential interaction of GRP78 and/or the UPR pathways with taxanes warrant
      larger studies.

PMID- 16912157
TI  - Presence of epidermal growth factor receptor gene T790M mutation as a minor clone
      in non-small cell lung cancer.
AB  - The threonine-to-methionine substitution at amino acid position 790 (T790M) of
      the epidermal growth factor receptor (EGFR) gene has been reported in progressing
      lesions after gefitinib treatment in non-small cell lung cancer (NSCLC) that
      causes sensitive tumors to become resistant to gefitinib. Alternatively, the EGFR
      T790M mutation might be present in small fractions of tumor cells before drug
      treatment, and the tumor cells harboring the T790M mutation might be enriched
      during the proliferation after drug treatment. We developed a mutant-enriched PCR
      assay to detect small fractions of cells with T790M mutation and used this
      technique to detect mutations in 280 NSCLCs, including gefitinib-treated 95
      cases. Although the direct sequencing detected only 1 T790M mutant case, the
      mutant-enriched PCR (confirmed to enrich one mutant out of 1 x 10(3) wild-type
      alleles) detected 9 additional cases among 280 cases. As linkage to
      clinicopathologic factors, the T790M mutation showed no bias for sex, smoking
      status, or histology but was significantly more frequent in advanced tumors (9 of
      111 cases) than in early-stage tumors (1 of 169 cases; P = 0.0013). Among
      gefitinib-treated cases, gefitinib-sensitive mutations were found in 30 cases.
      The T790M mutation was present in 3 of 7 no-responders with the gefitinib
      sensitive mutation and was not present in 19 responders (P = 0.014). Our results
      indicate that the T790M mutation is sometimes present in a minor population of
      tumor cells during the development of NSCLC and suggest that the detection of
      small fractions of T790M mutant alleles may be useful for predicting gefitinib
      resistance of NSCLCs with sensitive EGFR mutations.

PMID- 16912158
TI  - Disruption of scaffold attachment factor B1 leads to TBX2 up-regulation, lack of
      p19ARF induction, lack of senescence, and cell immortalization.
AB  - Scaffold attachment factor B1 (SAFB1) is a multifunctional protein, which has
      previously been implicated in breast cancer. Here, we show that genetic deletion
      of SAFB1 in mouse embryonic fibroblasts (MEF) leads to spontaneous
      immortalization and altered expression of two proteins involved in
      immortalization and escape from senescence: low levels of p19(ARF) and high
      levels of TBX2. Inactivation of TBX2 using a dominant-negative TBX2 resulted in
      up-regulation of p19(ARF) in SAFB1 knockout MEFs. SAFB1 loss also caused lack of
      contact inhibition, increased foci formation, and increased oncogene-induced
      anchorage-independent growth. These findings suggest that SAFB1 is a novel player
      in cellular immortalization and transformation.

PMID- 16912159
TI  - Mammalian target of rapamycin inhibition promotes response to epidermal growth
      factor receptor kinase inhibitors in PTEN-deficient and PTEN-intact glioblastoma
      cells.
AB  - The epidermal growth factor receptor (EGFR) is commonly amplified, overexpressed,
      and mutated in glioblastoma, making it a compelling molecular target for therapy.
      We have recently shown that coexpression of EGFRvIII and PTEN protein by
      glioblastoma cells is strongly associated with clinical response to EGFR kinase
      inhibitor therapy. PTEN loss, by dissociating inhibition of the EGFR from
      downstream phosphatidylinositol 3-kinase (PI3K) pathway inhibition, seems to act
      as a resistance factor. Because 40% to 50% of glioblastomas are PTEN deficient, a
      critical challenge is to identify strategies that promote responsiveness to EGFR
      kinase inhibitors in patients whose tumors lack PTEN. Here, we show that the
      mammalian target of rapamycin (mTOR) inhibitor rapamycin enhances the sensitivity
      of PTEN-deficient tumor cells to the EGFR kinase inhibitor erlotinib. In two
      isogenic model systems (U87MG glioblastoma cells expressing EGFR, EGFRvIII, and
      PTEN in relevant combinations, and SF295 glioblastoma cells in which PTEN protein
      expression has been stably restored), we show that combined EGFR/mTOR kinase
      inhibition inhibits tumor cell growth and has an additive effect on inhibiting
      downstream PI3K pathway signaling. We also show that combination therapy provides
      added benefit in promoting cell death in PTEN-deficient tumor cells. These
      studies provide strong rationale for combined mTOR/EGFR kinase inhibitor therapy
      in glioblastoma patients, particularly those with PTEN-deficient tumors.

PMID- 16912160
TI  - LKB1/STK11 suppresses cyclooxygenase-2 induction and cellular invasion through
      PEA3 in lung cancer.
AB  - We showed that the PEA3 transcriptional factor interacted with LKB1, a
      serine/threonine kinase, which is somatically mutated in lung cancer. This
      interaction occurred through the ETS domain of PEA3 and the kinase domain of
      LKB1. Mutation of LKB1 in lung cancer cells stabilized PEA3. Reintroduction of
      wild-type (WT) LKB1 into cells induced down-regulation of PEA3 and subsequently
      resulted in reduced cyclooxygenase-2 RNA and protein expression, whereas germ
      line and somatic LKB1 mutants were defective in this activity. LKB1
      phosphorylated PEA3 and promoted its degradation through a proteasome-mediated
      mechanism. Cells expressing mutant LKB1 possessed greater invasive potential
      compared with cells expressing WT LKB1. Increased invasion of cells with mutant
      LKB1 was partly due to PEA3 expression, as RNA interference inhibition of PEA3
      resulted in dramatic decrease of Matrigel invasion. However, forced expression of
      PEA3 resulted in down-regulation of epithelial markers and induction of
      mesenchymal markers. These results suggest that PEA3 stabilization due to LKB1
      inactivation could lead to epithelial/mesenchymal transition and greater lung
      cancer invasion potential.

PMID- 16912161
TI  - Ras-associated protein-1 regulates extracellular signal-regulated kinase
      activation and migration in melanoma cells: two processes important to melanoma
      tumorigenesis and metastasis.
AB  - Melanoma is one of the most devastating malignancies with a rising incidence and
      lack of effective treatments for advanced disease. Constitutive activation of the
      mitogen-activated protein kinase (MAPK) pathway and altered expression of
      alpha(v)beta(3) integrin are critical for melanoma development and progression.
      Ras-associated protein-1 (Rap1), a Ras family member of the small GTPases, has
      emerged as a key mediator in these two important processes. In this study, we
      have shown Rap1 activation in cells derived from two human metastatic melanomas
      and also in three of seven cutaneous metastatic melanoma tissues. We found
      increased extracellular signal-regulated kinase (ERK) activity in the tumors with
      detected Rap1 activity that interestingly harbored neither BRAF nor N-Ras
      mutation, suggesting a role for Rap1 in ERK activation in vivo. We also showed
      Rap1 and ERK activation by both hepatocyte growth factor (HGF) and 8CPT-2Me-cAMP
      (an activator of Epac, a Rap1 guanine nucleotide exchange factor) in two human
      melanoma cell lines. In addition, the activation of ERK by HGF was reduced, at
      least in part, by small interfering RNAs against Rap1 and a dominant-negative
      Rap1. Finally, a functional role for Rap1 activation was shown by Rap1-induced
      alpha(v)beta(3) integrin activation and consequent increased melanoma cell
      migration in vitro. Taken together, these results show that Rap1 is involved in
      the activation of MAPK pathway and integrin activation in human melanoma and
      suggest a potential role for Rap1 in melanoma tumorigenesis and metastasis.

PMID- 16912162
TI  - Synergy of p53 and Rb deficiency in a conditional mouse model for metastatic
      prostate cancer.
AB  - Pathways mediated by p53 and Rb are frequently altered in aggressive human
      cancers, including prostate carcinoma. To test directly the roles of p53 and Rb
      in prostate carcinogenesis, we have conditionally inactivated these genes in the
      prostate epithelium of the mouse. Inactivation of either p53 or Rb leads to
      prostatic intraepithelial neoplasia developing from the luminal epithelium by 600
      days of age. In contrast, inactivation of both genes results in rapidly
      developing (median survival, 226 days) carcinomas showing both luminal epithelial
      and neuroendocrine differentiation. The resulting neoplasms are highly
      metastatic, resistant to androgen depletion from the early stage of development,
      and marked with multiple gene expression signatures commonly found in human
      prostate carcinomas. Interestingly, gains at 4qC3 and 4qD2.2 and loss at 14qA2
      qD2 have been consistently found by comparative genomic hybridization. These loci
      contain such human cancer-related genes as Nfib, L-myc, and Nkx3.1, respectively.
      Our studies show a critical role for p53 and Rb deficiency in prostate
      carcinogenesis and identify likely secondary genetic alterations. The new
      genetically defined model should be particularly valuable for providing new
      molecular insights into the pathogenesis of human prostate cancer.

PMID- 16912163
TI  - Epigenetic silencing of the tumor suppressor cystatin M occurs during breast
      cancer progression.
AB  - Cystatin M is a secreted inhibitor of lysosomal cysteine proteases. Several lines
      of evidence indicate that cystatin M is a tumor suppressor important in breast
      malignancy; however, the mechanism(s) that leads to inactivation of cystatin M
      during cancer progression is unknown. Inspection of the human cystatin M locus
      uncovered a large and dense CpG island within the 5' region of this gene (termed
      CST6). Analysis of cultured human breast tumor lines indicated that cystatin M
      expression is either undetectable or in low abundance in several lines; however,
      enhanced gene expression was measured in cells cultured on the DNA demethylating
      agent 5-aza-2'-deoxycytidine (5-aza-dC). Increased cystatin M expression does not
      correlate with a cytotoxic response to 5-aza-dC; rather, various molecular
      approaches indicated that the CST6 gene was aberrantly methylated in these tumor
      lines as well as in primary breast tumors. Moreover, 60% (12 of 20) of primary
      tumors analyzed displayed CST6 hypermethylation, indicating that this aberrant
      characteristic is common in breast malignancies. Finally, preinvasive and
      invasive breast tumor cells were microdissected from nine archival breast cancer
      specimens. Of the five tumors displaying CST6 gene methylation, four tumors
      displayed methylation in both ductal carcinoma in situ and invasive breast
      carcinoma lesions and reduced expression of cystatin M in these tumors was
      confirmed by immunohistochemistry. In summary, this study establishes that the
      tumor suppressor cystatin M is a novel target for epigenetic silencing during
      mammary tumorigenesis and that this aberrant event can occur before development
      of invasive breast cancer.

PMID- 16912165
TI  - Identifying allelic loss and homozygous deletions in pancreatic cancer without
      matched normals using high-density single-nucleotide polymorphism arrays.
AB  - Recent advances in oligonucleotide arrays and whole-genome complexity reduction
      data analysis now permit the evaluation of tens of thousands of single-nucleotide
      polymorphisms simultaneously for a genome-wide analysis of allelic status. Using
      these arrays, we created high-resolution allelotype maps of 26 pancreatic cancer
      cell lines. The areas of heterozygosity implicitly served to reveal regions of
      allelic loss. The array-derived maps were verified by a panel of 317
      microsatellite markers used in a subset of seven samples, showing a 97.1%
      concordance between heterozygous calls. Three matched tumor/normal pairs were
      used to estimate the false-negative and potential false-positive rates for
      identifying loss of heterozygosity: 3.6 regions (average minimal region of loss,
      720,228 bp) and 2.3 regions (average heterozygous gap distance, 4,434,994 bp) per
      genome, respectively. Genomic fractional allelic loss calculations showed that
      cumulative levels of allelic loss ranged widely from 17.1% to 79.9% of the
      haploid genome length. Regional increases in "NoCall" frequencies combined with
      copy number loss estimates were used to identify 41 homozygous deletions (19
      first reports), implicating an additional 13 regions disrupted in pancreatic
      cancer. Unexpectedly, 23 of these occurred in just two lines (BxPc3 and
      MiaPaCa2), suggesting the existence of at least two subclasses of chromosomal
      instability (CIN) patterns, distinguished here by allelic loss and copy number
      changes (original CIN) and those also highly enriched in the genomic "holes" of
      homozygous deletions (holey CIN). This study provides previously unavailable high
      resolution allelotype and deletion breakpoint maps in widely shared pancreatic
      cancer cell lines and effectively eliminates the need for matched normal tissue
      to define informative loci.

PMID- 16912164
TI  - Molecular inversion probe analysis of gene copy alterations reveals distinct
      categories of colorectal carcinoma.
AB  - Genomic instability is a major feature of neoplastic development in colorectal
      carcinoma and other cancers. Specific genomic instability events, such as
      deletions in chromosomes and other alterations in gene copy number, have
      potential utility as biologically relevant prognostic biomarkers. For example,
      genomic deletions on chromosome arm 18q are an indicator of colorectal carcinoma
      behavior and potentially useful as a prognostic indicator. Adapting a novel
      genomic technology called molecular inversion probes which can determine gene
      copy alterations, such as genomic deletions, we designed a set of probes to
      interrogate several hundred individual exons of >200 cancer genes with an overall
      distribution covering all chromosome arms. In addition, >100 probes were designed
      in close proximity of microsatellite markers on chromosome arm 18q. We analyzed a
      set of colorectal carcinoma cell lines and primary colorectal tumor samples for
      gene copy alterations and deletion mutations in exons. Based on clustering
      analysis, we distinguished the different categories of genomic instability among
      the colorectal cancer cell lines. Our analysis of primary tumors uncovered
      several distinct categories of colorectal carcinoma, each with specific patterns
      of 18q deletions and deletion mutations in specific genes. This finding has
      potential clinical ramifications given the application of 18q loss of
      heterozygosity events as a potential indicator for adjuvant treatment in stage II
      colorectal carcinoma.

PMID- 16912166
TI  - Emergence of androgen independence at early stages of prostate cancer progression
      in Nkx3.1; Pten mice.
AB  - Although androgen deprivation therapy is a widely used treatment for patients
      with advanced prostate cancer, it ultimately results in the emergence of a
      hormone-refractory disease that is invariably fatal. To provide insights into the
      genesis of this disease, we have employed an in vivo model to investigate how and
      when prostate epithelial cells can acquire the ability to survive and proliferate
      in the absence of androgens. In particular, we have been studying the evolution
      of androgen independence in Nkx3.1; Pten mutant mice, which develop prostatic
      intraepithelial neoplasia and adenocarcinoma as a consequence of aging, as well
      as androgen-independent phenotypes following castration. We now find that the
      prostate epithelial cells from these Nkx3.1; Pten mutant mice are capable of
      surviving and proliferating in the absence of androgens and that they develop
      androgen-independent phenotypes well before they display overt prostatic
      intraepithelial neoplasia or cancer phenotypes. Our findings in this mouse model
      show that acquisition of androgen independence can be uncoupled from overt cancer
      progression and raise the possibility that hormone-refractory disease can arise
      at early stages of prostate carcinogenesis.

PMID- 16912167
TI  - Tsc1 haploinsufficiency without mammalian target of rapamycin activation is
      sufficient for renal cyst formation in Tsc1+/- mice.
AB  - Tuberous sclerosis complex (TSC) is caused by mutations in either the TSC1 or
      TSC2 gene. Both genes are generally considered to act as tumor suppressors that
      fulfill Knudson's "two-hit hypothesis" and that function within the
      phosphoinositide 3-kinase-Akt-mammalian target of rapamycin (mTOR) pathway. We
      previously generated Tsc1(+/-) mice that are predisposed to renal cysts, which
      develop into cystadenomas and renal cell carcinomas. Here, we identified somatic
      Tsc1 mutations (second hits) in approximately 80% of cystadenomas and renal cell
      carcinomas, but only 31.6% of cysts from Tsc1(+/-) mice (P < 0.0003), raising the
      possibility that haploinsufficiency for Tsc1 plays a role in cyst formation.
      Consistent with this proposal, many cysts showed little or no staining for
      phosphorylated mTOR (53%) and phosphorylated S6 ribosomal protein (37%), whereas
      >90% of cystadenomas and renal cell carcinomas showed strong staining for both
      markers (P < 0.0005). We also sought somatic mutations in renal lesions from
      Tsc1(+/-) Blm(-/-) mice that have a high frequency of somatic loss of
      heterozygosity, thereby facilitating the detection of second hits. We also found
      significantly less somatic mutations in cysts as compared with cystadenomas and
      renal cell carcinomas from these mice (P = 0.017). Our data indicate that
      although activation of the mTOR pathway is an important step in Tsc-associated
      renal tumorigenesis, it may not be the key initiating event in this process.

PMID- 16912168
TI  - MIRA-assisted microarray analysis, a new technology for the determination of DNA
      methylation patterns, identifies frequent methylation of homeodomain-containing
      genes in lung cancer cells.
AB  - We present a straightforward and comprehensive approach for DNA methylation
      analysis in mammalian genomes. The methylated-CpG island recovery assay (MIRA),
      which is based on the high affinity of the MBD2/MBD3L1 complex for methylated
      DNA, has been used to detect cell type-dependent differences in DNA methylation
      on a microarray platform. The procedure has been verified and applied to identify
      a series of novel candidate lung tumor suppressor genes and potential DNA
      methylation markers that contain methylated CpG islands. One gene of particular
      interest was DLEC1, located at a commonly deleted area on chromosome 3p22-p21.3,
      which was frequently methylated in primary lung cancers and melanomas. Among the
      identified methylated genes, homeodomain-containing genes were unusually frequent
      (11 of the top 50 hits) and were targeted on different chromosomes. These genes
      included LHX2, LHX4, PAX7, HOXB13, LBX1, SIX2, HOXD3, DLX1, HOXD1, ONECUT2, and
      PAX9. The data show that MIRA-assisted microarray analysis has a low false
      positive rate and has the capacity to catalogue methylated CpG islands on a
      genome-wide basis. The results support the hypothesis that cancer-associated DNA
      methylation events do not occur randomly throughout the genome but at least some
      are targeted by specific mechanisms.

PMID- 16912169
TI  - HuR contributes to cyclin E1 deregulation in MCF-7 breast cancer cells.
AB  - Many cancers overexpress cyclin E1 and its tumor-specific low molecular weight
      (LMW) isoforms. However, the mechanism of cyclin E1 deregulation in cancers is
      still not well understood. We show here that the mRNA-binding protein HuR
      increases cyclin E1 mRNA stability in MCF-7 breast carcinoma cells. Thus, mRNA
      stabilization may be a key event in the deregulation of cyclin E1 in MCF-7 cells.
      Compared with MCF10A immortalized breast epithelial cells, MCF-7 cells
      overexpress full-length cyclin E1 and its LMW isoforms and exhibit increased
      cyclin E1 mRNA stability. Increased mRNA stability is associated with a stable
      adenylation state and an increased ratio of cytoplasmic versus nuclear HuR. UV
      cross-link competition and UV cross-link immunoprecipitation assays verified that
      HuR specifically bound to the cyclin E1 3'-untranslated region. Knockdown of HuR
      with small interfering RNA (siRNA) in MCF-7 cells decreased cyclin E1 mRNA half
      life (t(1/2)) and its protein level: a 22% decrease for the full-length isoforms
      and 80% decrease for the LMW isoforms. HuR siRNA also delayed G(1)-S phase
      transition and inhibited MCF-7 cell proliferation, which was partially recovered
      by overexpression of a LMW isoform of cyclin E1. Overexpression of HuR in MCF10A
      cells increased cyclin E1 mRNA t(1/2) and its protein level. Taken together, our
      data show that HuR critically contributes to cyclin E1 overexpression and its
      growth-promoting function, at least in part by increasing cyclin E1 mRNA
      stability, which provides a new mechanism of cyclin E1 deregulation in breast
      cancer.

PMID- 16912170
TI  - Plasticity in urokinase-type plasminogen activator receptor (uPAR) display in
      colon cancer yields metastable subpopulations oscillating in cell surface uPAR
      density--implications in tumor progression.
AB  - It is becoming increasingly clear that tumor growth and progression is not
      entirely due to genetic aberrations but also reflective of tumor cell plasticity.
      It follows therefore that proteins contributing to tumor progression oscillate in
      their expression a contention yet to be shown. Because the urokinase-type
      plasminogen activator receptor (uPAR) promotes tumor growth and invasion, we
      determined whether its expression is itself plastic. In fluorescence-activated
      cell sorting (FACS), three independent colon cancer clonal populations revealed
      the expected Gaussian distribution for cell surface uPAR display. However,
      subcloning of cells collected from the trailing edge of the FACS yielded
      subpopulations, displaying low cell surface uPAR number. Importantly, these
      subclones spontaneously reverted to cells enriched in uPAR display, indicating a
      metastable phenotype. uPAR display plasticity was associated with divergent in
      vivo behavior with weak tumor growth and progression segregating with receptor
      deficiency. Mechanistically, reduced uPAR display reflected not repressed gene
      expression but a switch in uPAR protein trafficking from membrane insertion to
      shedding. To our knowledge, this is the first demonstration that uPAR cell
      surface density is oscillatory and we propose that such an event might well
      contribute to tumor progression.

PMID- 16912172
TI  - Met, the hepatocyte growth factor receptor, localizes to the nucleus in cells at
      low density.
AB  - Some breast cancer cases in our previous immunohistochemical studies show Met
      expression in the nucleus. Given nuclear localization of other receptor tyrosine
      kinases, we proceeded to investigate Met. Nuclear Met is seen in numerous cell
      lines and in germinal regions of many tissues using four unique antibodies. Cell
      fractionation reveals a 60-kDa band recognized by COOH-terminal Met antibodies
      that is present independent of hepatocyte growth factor treatment. Green
      fluorescent protein (GFP) fusion proteins of the cytoplasmic domain of Met
      transfected into HEK293 cells are found in the nucleus whereas the full-length
      Met-GFP fusion is membranous. Further deletions of the Met-GFP fusions identify a
      region of the juxtamembrane domain required for nuclear translocation. In a CaCo2
      cell line model for epithelial maturation, we find that Met is initially nuclear,
      and then becomes membranous, after confluence. This work suggests processing of
      the Met receptor, analogous to ErbB4, resulting in the release of the cytoplasmic
      domain and its translocation to the nucleus in cells at low density.

PMID- 16912171
TI  - Analysis of host- and tumor-derived proteinases using a custom dual species
      microarray reveals a protective role for stromal matrix metalloproteinase-12 in
      non-small cell lung cancer.
AB  - We used a customized Affymetrix protease microarray (Hu/Mu ProtIn chip) designed
      to distinguish human and mouse genes to analyze the expression of proteases and
      protease inhibitors in lung cancer. Using an orthotopic lung cancer model, we
      showed that murine matrix metalloproteinase (MMP)-12, MMP-13, and cathepsin K
      were up-regulated in tumor tissue compared with normal mouse lung. To determine
      the relevance of stromal proteases detected using this model system, we compared
      the results to an analysis of human lung adenocarcinoma specimens using the U133
      Plus 2.0 Affymetrix microarray. MMP-12, MMP-13, and cathepsin K showed an
      increase in expression in human tumors compared with normal lung similar to that
      seen in the orthotopic model. Immunohistochemical analysis confirmed MMP-12
      expression in the stroma of human lung tumor samples. To determine the biological
      relevance of stromal MMP-12, murine Lewis lung carcinoma cells were injected into
      the tail vein of syngeneic wild-type (WT) and MMP-12-null mice. MMP-12-null and
      WT mice developed equivalent numbers of lung tumors; however, there was a 2-fold
      increase in the number of tumors that reached >2 mm in diameter in MMP-12-null
      mice compared with WT controls. The increase in tumor size correlated with an
      increase in CD31-positive blood vessels and a decrease in circulating levels of
      the K1-K4 species of angiostatin. These results show a protective role for
      stromal MMP-12 in lung tumor growth. The use of the Hu/Mu ProtIn chip allows us
      to distinguish tumor- and host-derived proteases and guides the further analysis
      of the significance of these genes in tumor progression.

PMID- 16912173
TI  - Hypoxia enhances lysophosphatidic acid responsiveness in ovarian cancer cells and
      lysophosphatidic acid induces ovarian tumor metastasis in vivo.
AB  - Lysophosphatidic acid (LPA) is elevated in ascites of ovarian cancer patients and
      stimulates growth and other activities of ovarian cancer cells in vitro. Tissue
      hypoxia is a critical factor for tumor aggressiveness and metastasis in cancers.
      We tested whether the ascites of ovarian cancer is hypoxic and whether hypoxia
      influences the effects of LPA on ovarian cancer cells. We found that ovarian
      ascitic fluids were hypoxic in vivo. Enhanced cellular responsiveness to LPA,
      including migration and/or invasion of ovarian cancer cells, was observed under
      hypoxic conditions. This enhancement could be completely blocked by geldanamycin
      or a small interfering RNA targeting hypoxia-inducible factor 1 alpha (HIF1
      alpha). LPA-induced cell migration required cytosolic phospholipase A(2)
      (cPLA(2)) and LPA stimulates cPLA(2) phosphorylation in a HIF1 alpha-dependent
      manner under hypoxia conditions. Furthermore, we show for the first time that
      exogenous LPA enhances tumor metastasis in an orthotopic ovarian cancer model and
      HIF alpha expression in tumors. 17-Dimethylaminoethylamino-17
      demethoxygeldanamycin (an inhibitor of the heat shock protein 90) effectively
      blocked LPA-induced tumor metastasis in vivo. Together, our data indicate that
      hypoxic conditions are likely to be pathologically important for ovarian cancer
      development. HIF1 alpha plays a critical role in enhancing and/or sensitizing the
      role of LPA on cell migration and invasion under hypoxic conditions, where
      cPLA(2) is required for LPA-induced cell migration.

PMID- 16912174
TI  - Coregulation of estrogen receptor by ERBB4/HER4 establishes a growth-promoting
      autocrine signal in breast tumor cells.
AB  - Although crosstalk between cell-surface and nuclear receptor signaling pathways
      has been implicated in the development and progression of endocrine-regulated
      cancers, evidence of direct coupling of these signaling pathways has remained
      elusive. Here we show that estrogen promotes an association between extranuclear
      estrogen receptor alpha (ER) and the epidermal growth factor receptor (EGFR)
      family member ERBB4. Ectopically expressed as well as endogenous ERBB4 interacts
      with and potentiates ER transactivation, indicating that the ERBB4/ER interaction
      is functional. Estrogen induces nuclear translocation of the proteolytic
      processed ERBB4 intracellular domain (4ICD) and nuclear translocation of 4ICD
      requires functional ligand-bound ER. The nuclear ER/4ICD complex is selectively
      recruited to estrogen-inducible gene promoters such as progesterone receptor
      (PgR) and stromal cell-derived factor 1 (SDF-1) but not to trefoil factor 1
      precursor (pS2). Consistent with 4ICD-selective promoter binding, suppression of
      ERBB4 expression by interfering RNA shows that 4ICD coactivates ER transcription
      at the PgR and SDF-1 but not the pS2 promoter. Significantly, ERBB4 itself is an
      estrogen-inducible gene and the ERBB4 promoter harbors a consensus estrogen
      response element (ERE) half-site with overlapping activator protein-1 elements
      that bind ER and 4ICD in response to estrogen. Using a cell proliferation assay
      and a small interfering RNA approach, we show that ERBB4 expression is required
      for the growth-promoting action of estrogen in the T47D breast cancer cell line.
      Our results indicate that ERBB4 is a unique coregulator of ER, directly coupling
      extranuclear and nuclear estrogen actions in breast cancer. We propose that the
      contribution of an autocrine ERBB4/ER signaling pathway to tumor growth and
      therapeutic response should be considered when managing patients with ER-positive
      breast cancer.

PMID- 16912175
TI  - Genome-wide expression profiling reveals EBV-associated inhibition of MHC class I
      expression in nasopharyngeal carcinoma.
AB  - To identify the molecular mechanisms by which EBV-associated epithelial cancers
      are maintained, we measured the expression of essentially all human genes and all
      latent EBV genes in a collection of 31 laser-captured, microdissected
      nasopharyngeal carcinoma (NPC) tissue samples and 10 normal nasopharyngeal
      tissues. Global gene expression profiles clearly distinguished tumors from normal
      healthy epithelium. Expression levels of six viral genes (EBNA1, EBNA2, EBNA3A,
      EBNA3B, LMP1, and LMP2A) were correlated among themselves and strongly inversely
      correlated with the expression of a large subset of host genes. Among the human
      genes whose inhibition was most strongly correlated with increased EBV gene
      expression were multiple MHC class I HLA genes involved in regulating immune
      response via antigen presentation. The association between EBV gene expression
      and inhibition of MHC class I HLA expression implies that antigen display is
      either directly inhibited by EBV, facilitating immune evasion by tumor cells,
      and/or that tumor cells with inhibited presentation are selected for their
      ability to sustain higher levels of EBV to take maximum advantage of EBV oncogene
      mediated tumor-promoting actions. Our data clearly reflect such tumor promotion,
      showing that deregulation of key proteins involved in apoptosis (BCL2-related
      protein A1 and Fas apoptotic inhibitory molecule), cell cycle checkpoints (AKIP,
      SCYL1, and NIN), and metastasis (matrix metalloproteinase 1) is closely
      correlated with the levels of EBV gene expression in NPC.

PMID- 16912176
TI  - Transforming growth factor-beta promotes invasion in tumorigenic but not in
      nontumorigenic human prostatic epithelial cells.
AB  - Transforming growth factor-beta (TGF-beta) is a pleiotropic growth factor with
      actions that are dependent on circumstances, including dose, target cell type,
      and context. TGF-beta can elicit both growth-promoting and growth-suppressive
      activities. In normal tissues, TGF-beta generally acts to restrict growth and
      maintain differentiation. However, during tumorigenesis, changes in TGF-beta
      expression and cellular responses can promote tumorigenesis. The present study
      examines the effects of TGF-beta on the nontumorigenic human prostatic epithelial
      cell line BPH1 and on three derivative tumorigenic sublines BPH1(CAFTD)1,
      BPH1(CAFTD)3, and BPH1(CAFTD)5. The data show that TGF-beta has different effects
      on the nontumorigenic and tumorigenic cells. The nontumorigenic cells are growth
      inhibited by TGF-beta. In contrast, the tumorigenic sublines are not growth
      inhibited but instead undergo an epithelial to mesenchymal transformation (EMT)
      in response to TGF-beta. The tumorigenic lines show constitutively elevated
      levels of phosphorylated Akt, which modulates their response to TGF-beta by
      blocking Smad3 and p21 nuclear translocation. On TGF-beta stimulation of the
      tumorigenic sublines, the activated Akt allows the cell to escape cell cycle
      arrest. The phosphatidylinositol 3-kinase/Akt pathway is also involved in TGF
      beta-induced EMT, defined here by induction of vimentin expression and enhanced
      cellular motility. In vivo, tumorigenic cells with constitutively active TGF-beta
      signaling show increased invasion with EMT, which express vimentin, located
      specifically at the invasive front of the tumor. These data indicate that
      following malignant transformation TGF-beta can play a direct role in promoting
      prostatic cancer and further that these responses are context specific in vivo.

PMID- 16912177
TI  - Cortactin overexpression regulates actin-related protein 2/3 complex activity,
      motility, and invasion in carcinomas with chromosome 11q13 amplification.
AB  - Carcinoma cell motility and invasion are prerequisites for tumor cell metastasis,
      which requires regulation of the actin cytoskeleton. Cortactin is an actin
      related protein 2/3 (Arp2/3) complex-activating and filamentous (F)-actin-binding
      protein that is implicated in tumor cell motility and metastasis, partially by
      its ability to become tyrosine phosphorylated. Cortactin is encoded by the CTTN
      gene and maps to chromosome 11q13, a region amplified in many carcinomas,
      including head and neck squamous cell carcinoma (HNSCC). CTTN gene amplification
      is associated with lymph node metastasis and poor patient outcome, and cortactin
      overexpression enhances motility in tumor cells lacking 11q13 amplification.
      However, a direct link between increased motility and invasion has not been
      reported in tumor cells with chromosome 11q13 amplification and cortactin
      overexpression. In this study, we have examined the relationship between CTTN
      amplification and tumor cell motility in HNSCC. In 11 of 39 (28%) HNSCC cases,
      cortactin overexpression determined by immunohistochemistry correlates with lymph
      node metastasis and CTTN gene amplification. HNSCC cells containing cortactin
      gene amplification and protein overexpression display increased binding and
      activation of Arp2/3 complex, and were more motile and invasive than HNSCC cells
      lacking CTTN amplification. Down-regulation of cortactin expression in CTTN
      amplified HNSCC cells by small interfering RNA impairs HNSCC motility and
      invasion. Treatment of HNSCC cells with the epidermal growth factor receptor
      inhibitor gefitinib inhibits HNSCC motility and down-regulates cortactin tyrosine
      phosphorylation. These data suggest that cortactin may be a valid prognostic and
      therapeutic marker for invasive and metastatic HNSCC and other carcinomas with
      11q13 amplification.

PMID- 16912178
TI  - Granulocyte colony-stimulating factor and granulocyte-macrophage colony
      stimulating factor promote malignant growth of cells from head and neck squamous
      cell carcinomas in vivo.
AB  - Granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony
      stimulating factor (GM-CSF) are used to ameliorate cancer therapy-induced
      neutropenia and mucositis. Yet, first data in head and neck squamous cell
      carcinoma (HNSCC) indicate an impaired long-term prognosis on G-CSF treatment,
      and previous studies showed a contribution of both factors to the progression of
      human epithelial tumors. Therefore, we investigate the role of G-CSF and GM-CSF
      in progression of tumor cells from human HNSCC. Both factors stimulated
      proliferation and migration of tumor cell lines established from patient tumors
      expressing G-CSF and GM-CSF and/or their receptors. Blockade of G-CSF and GM-CSF
      inhibited tumor cell invasion in a three-dimensional organotypic culture model.
      The contribution of both factors to tumor malignancy was further confirmed in
      nude mouse transplants in vivo. Invasive and malignant growth yielding a similar
      tumor phenotype as the original patient tumor was exclusively observed in G-CSF-
      and GM-CSF-expressing tumors and was associated with enhanced and persistent
      angiogenesis and enhanced inflammatory cell recruitment. Although factor-negative
      tumors grew somewhat faster, they were characterized by lack of invasion, reduced
      and transient angiogenesis, and large necrotic areas. These data provide evidence
      for a progression-promoting effect of G-CSF and GM-CSF in human HNSCC and suggest
      further detailed evaluation of their use in the therapy of these tumors.

PMID- 16912179
TI  - Real-time imaging of lymphogenic metastasis in orthotopic human breast cancer.
AB  - Metastatic spread to regional lymph nodes is one of the earliest events of tumor
      cell dissemination and presents a most significant prognostic factor for
      predicting survival of cancer patients. Real-time in vivo imaging of the spread
      of tumor cells through the lymphatic system can enhance our understanding of the
      metastatic process. Herein, we describe the use of in vivo fluorescence
      microscopy imaging to monitor the progression of lymph node metastasis as well as
      the course of spontaneous metastasis through the lymphatic system of orthotopic
      MDA-MB-231 human breast cancer tumors in severe combined immunodeficient mice.
      High-resolution noninvasive visualization of metastasizing cancer cells in the
      inguinal lymph nodes was achieved using cells expressing high levels of red
      fluorescent protein. Sequential imaging of these lymph nodes revealed the initial
      invasion of the tumor cells through the lymphatic system into the subcapsular
      sinuses followed by intrusion into the parenchyma of the nodes. FITC-dextran
      injected i.d. in the tumor area enabled simultaneous tracking of lymphatic
      vessels, labeled in green, and disseminated red cancer cells within these
      vessels. Fast snapshots of spontaneously metastasizing cells in the lymphatic
      vessels monitored the movement of a few tumor cells and the development of clumps
      clustered at lymphatic vessel junctions. Quantification of high interstitial
      fluid pressure (IFP) in the tumors and fast drainage rates of the FITC-dextran
      into the peritumoral lymphatic vessels suggested an IFP-induced intravasation
      into the lymphatic system. This work presents unprecedented live fluorescence
      images that may help to clarify the steps occurring in the course of spontaneous
      lymphogenic metastasis.

PMID- 16912180
TI  - Autocrine/paracrine platelet-derived growth factor regulates proliferation of
      neural progenitor cells.
AB  - Growth factors play an important role in regulating neural stem cell
      proliferation and differentiation. This study shows that platelet-derived growth
      factor (PDGF) induces a partial differentiation of neural stem/progenitor cells
      (NSPCs) in the absence of other mitogens in vitro. NSPCs thus acquire an immature
      morphology and display markers for both neurons and glia. In addition, these
      cells do not readily mature in the absence of further stimuli. When NSPC cultures
      treated with PDGF were exposed to additional differentiation factors, however,
      the differentiation proceeded into neurons, astrocytes, and oligodendrocytes. We
      find that NSPC cultures are endowed with an endogenous PDGF-BB production. The
      PDGF-BB expression peaks during early differentiation and is present both in cell
      lysates and in conditioned medium, allowing for autocrine as well as paracrine
      signaling. When the NSPC-derived PDGF was inhibited, progenitor cell numbers
      decreased, showing that PDGF is involved in NSPC expansion. Addition of a PDGF
      receptor (PDGFR) inhibitor resulted in a more rapid differentiation. Neurons and
      oligodendrocytes appeared earlier and had more elaborate processes than in
      control cultures where endogenous PDGFR signaling was not blocked. Our
      observations point to PDGF as an inducer of partial differentiation of NSPC that
      also sustains progenitor cell division. Such an intermediate stage in stem cell
      differentiation is of relevance for the understanding of brain tumor development
      because autocrine PDGF stimulation is believed to drive malignant conversion of
      central nervous system progenitor cells.

PMID- 16912181
TI  - Wilms' tumor 1 and signal transducers and activators of transcription 3
      synergistically promote cell proliferation: a possible mechanism in sporadic
      Wilms' tumor.
AB  - Transcription factor Wilms' tumor 1 (WT1) was originally identified as a tumor
      suppressor for Wilms' tumor, but it is also overexpressed in a variety of cancer
      cells, suggesting a potential oncogenic function of WT1. It is important to
      understand molecular mechanisms underlying these dual functions of WT1 in
      tumorigenesis. In the current study, we report a synergistic role for signal
      transducers and activators of transcription 3 (STAT3) and WT1 in tumor
      development, including Wilms' tumor. STAT3 interacts with WT1 through its
      conserved domains both in vitro and in vivo. When STAT3 is activated, expression
      of WT1 enhances STAT3 transcriptional activity. Overexpression of WT1 and STAT3CA
      in NIH 3T3 increases the expression level of STAT3 target genes, including cyclin
      D1 and Bcl-xL, which results in an advantage of cell proliferation. Our results
      suggest that in the presence of activated STAT3, WT1 promotes cell proliferation
      instead of suppressing cell proliferation. Strikingly, STAT3 translocates to the
      nucleus and interacts with WT1 in a variety of primary Wilms' tumor cells,
      raising the hypothesis that WT1 and activated STAT3 in Wilms' tumor accelerate
      tumorigenesis.

PMID- 16912182
TI  - Tyrosine kinase Etk/BMX is up-regulated in human prostate cancer and its
      overexpression induces prostate intraepithelial neoplasia in mouse.
AB  - The nonreceptor tyrosine kinase Etk/BMX was originally identified from the human
      prostate xenograft CWR22. Here, we report that Etk is up-regulated in human
      prostate tumor specimens surveyed. Knocking down Etk expression by a specific
      small interfering RNA (siRNA) in prostate cancer cells attenuates cell
      proliferation, suggesting an essential role of Etk for prostate cancer cell
      survival and growth. Targeted expression of Etk in mouse prostate epithelium
      results in pathologic changes resembling human prostatic intraepithelial
      neoplasia, indicating that up-regulation of Etk may contribute to prostate cancer
      development. A marked increase of luminal epithelial cell proliferation was
      observed in the Etk transgenic prostate, which may be attributed in part to the
      elevated activity of Akt and signal transducers and activators of transcription 3
      (STAT3). More interestingly, the expression level of acetyltransferase cyclic AMP
      responsive element binding protein-binding protein (CBP) is also increased in the
      Etk transgenic prostate as well as in a prostate cancer cell line overexpressing
      Etk, concomitant with elevated histone 3 acetylation at lysine 18 (H3K18Ac). Down
      modulation of Etk expression by a specific siRNA leads to a decrease of H3
      acetylation in prostate cancer cell lines. Our data suggest that Etk may also
      modulate chromatin remodeling by regulating the activity of acetyltransferases,
      such as CBP. Given that Etk may exert its effects in prostate through modulation
      of multiple signaling pathways altered in human prostate cancer, the Etk
      transgenic mouse model may be a useful tool for studying the functions of Etk and
      identification of new molecular markers and drug targets relevant to human
      diseases.

PMID- 16912183
TI  - Imaging steps of lymphatic metastasis reveals that vascular endothelial growth
      factor-C increases metastasis by increasing delivery of cancer cells to lymph
      nodes: therapeutic implications.
AB  - Preclinical and clinical studies positively correlate the expression of vascular
      endothelial growth factor (VEGF)-C in tumors and the incidence of lymph node
      metastases. However, how VEGF-C regulates individual steps in the transport of
      tumor cells from the primary tumor to the draining lymph nodes is poorly
      understood. Here, we image and quantify these steps in tumors growing in the tip
      of the mouse ear using intravital microscopy of the draining lymphatic vessels
      and lymph node, which receives spontaneously shed tumor cells. We show that VEGF
      C overexpression in cancer cells induces hyperplasia in peritumor lymphatic
      vessels and increases the volumetric flow rate in lymphatics at the base of the
      ear by 40%. The increases in lymph flow rate and peritumor lymphatic surface area
      enhance the rate of tumor cell delivery to lymph nodes, leading to a 200-fold
      increase in cancer cell accumulation in the lymph node and a 4-fold increase in
      lymph node metastasis. In our model, VEGF-C overexpression does not confer any
      survival or growth advantage on cancer cells. We also show that an anti-VEGF
      receptor (VEGFR)-3 antibody reduces both lymphatic hyperplasia and the delivery
      of tumor cells to the draining lymph node, leading to a reduction in lymph node
      metastasis. However, this treatment is unable to prevent the growth of tumor
      cells already seeded in lymph nodes. Collectively, our results indicate that VEGF
      C facilitates lymphatic metastasis by increasing the delivery of cancer cells to
      lymph nodes and therapies directed against VEGF-C/VEGFR-3 signaling target the
      initial steps of lymphatic metastasis.

PMID- 16912184
TI  - Functional interaction of the retinoblastoma and Ini1/Snf5 tumor suppressors in
      cell growth and pituitary tumorigenesis.
AB  - The Ini1 subunit of the SWI/SNF chromatin remodeling complex suppresses formation
      of malignant rhabdoid tumors in humans and mice. Transduction of Ini1 into Ini1
      deficient tumor-derived cell lines has indicated that Ini1 arrests cell growth,
      controls chromosomal ploidy, and suppresses tumorigenesis by regulating
      components of the retinoblastoma (Rb) signaling pathway. Furthermore, conditional
      inactivation of Ini1 in mouse fibroblasts alters the expression of various Rb-E2F
      regulated genes, indicating that endogenous Ini1 levels may control Rb signaling
      in cells. We have reported previously that loss of one allele of Ini1 in mouse
      fibroblasts results only in a 15% to 20% reduction in total Ini1 mRNA levels due
      to transcriptional compensation by the remaining Ini1 allele. Here, we examine
      the effects of Ini1 haploinsufficiency on cell growth and immortalization in
      mouse embryonic fibroblasts. In addition, we examine pituitary tumorigenesis in
      Rb-Ini1 compound heterozygous mice. Our results reveal that heterozygosity for
      Ini1 up-regulates cell growth and immortalization and that exogenous Ini1 down
      regulates the growth of primary cells in a Rb-dependent manner. Furthermore, loss
      of Ini1 is redundant with loss of Rb function in the formation of pituitary
      tumors in Rb heterozygous mice and leads to the formation of large, atypical
      Rb(+/-) tumor cells lacking adrenocorticotropic hormone expression. These results
      confirm in vivo the relationship between Rb and Ini1 in tumor suppression and
      indicate that Ini1 plays a role in maintaining the morphologic and functional
      differentiation of corticotrophic cells.

PMID- 16912185
TI  - Multiple acquired renal carcinoma tumor capabilities abolished upon silencing of
      ADAM17.
AB  - Malignancy is a manifestation of acquired defects in regulatory circuits that
      direct normal cell proliferation and homeostasis. Most of these circuits operate
      through cell autonomous pathways, whereas others potentially involve the
      neighboring microenvironment. We report that the metalloprotease ADAM17 plays a
      pivotal role in several acquired tumor cell capabilities by mediating the
      availability of soluble transforming growth factor-alpha, an epidermal growth
      factor receptor (EGFR) ligand, and thus the establishment of a key autocrine
      signaling pathway. Silencing of ADAM17 in human renal carcinoma cell lines
      corrects critical features associated with cancer cells, including growth
      autonomy, tumor inflammation, and tissue invasion. Highly malignant renal
      carcinoma cancer cells fail to form in vivo tumors in the absence of ADAM17,
      confirming the essential function of this molecule in tumorigenesis. These data
      show that ligand shedding is a crucial step in endogenous EGFR activation and
      endorse prospective therapeutic strategies targeting ADAM17 in human cancer.

PMID- 16912186
TI  - Role of focal adhesion kinase and phosphatidylinositol 3'-kinase in integrin
      fibronectin receptor-mediated, matrix metalloproteinase-1-dependent invasion by
      metastatic prostate cancer cells.
AB  - alpha(5)beta(1) Integrin interacts with the PHSRN sequence of plasma fibronectin,
      causing constitutive invasion by human prostate cancer cells. Inhibition of this
      process reduces tumorigenesis and prevents metastasis and recurrence. In this
      study, naturally serum-free basement membranes were used as in vitro invasion
      substrates. Immunoassays were employed to dissect the roles of focal adhesion
      kinase (FAK), phosphatidylinositol 3'-kinase (PI3K), and protein kinase Cdelta
      (PKC delta) in alpha(5)beta(1)-mediated, matrix metalloproteinase-1 (MMP-1)
      dependent invasion by metastatic human DU 145 prostate cancer cells. We found
      that a peptide composed of the PHSRN sequence induced rapid FAK phosphorylation
      at Tyr(397) (Y397), a site whose phosphorylation is associated with kinase
      activation. The technique of RNA silencing [small interfering RNA (siRNA)]
      confirmed the role of FAK in PHSRN-induced invasion. PHSRN also induced the
      association of the p85-regulatory subunit of PI3K with FAK at a time
      corresponding to FAK phosphorylation and activation, and maximal PI3K activity
      occurred at this same time. The necessity of PI3K activity in both PHSRN-induced
      invasion and MMP-1 expression was confirmed by using specific PI3K inhibitors. By
      employing a specific inhibitor, Rottlerin, and by using siRNA, we also found that
      PKC delta, a PI3K substrate found in focal adhesions, functions in PHSRN-induced
      invasion. In addition, the induction of MMP-1 in PHSRN-treated DU 145 cells was
      shown by immunoblotting, and the role of MMP-1 in PHSRN-induced invasion was
      confirmed by the use of blocking anti-MMP-1 monoclonal antibody. Finally, a close
      temporal correspondence was observed between PHSRN-induced invasion and PHSRN
      induced MMP-1 activity in DU 145 cells.

PMID- 16912187
TI  - Cellular retinoic acid-binding protein II is a direct transcriptional target of
      MycN in neuroblastoma.
AB  - Neuroblastoma is a heterogeneous disease in which 22% of tumors show MycN
      oncogene amplification and are associated with poor clinical outcome. MycN is a
      transcription factor that regulates the expression of a number of proteins that
      affect the clinical behavior of neuroblastoma. We report here that cellular
      retinoic acid-binding protein II (CRABP-II) is a novel MycN target, expressed at
      significantly higher levels in primary neuroblastoma tumors with mycN oncogene
      amplification as compared with non-MycN-amplified tumors. Moreover, regulated
      induction and repression of MycN in a neuroblastoma-derived cell line resulted in
      temporal and proportionate expression of CRABP-II. CRABP-II is expressed in
      several cancers, but its role in tumorigenesis has not been elucidated. We show
      that MycN binds to the promoter of CRABP-II and induces CRABP-II transcription
      directly. In addition, CRABP-II-transfected neuroblastoma cell lines show an
      increase in MycN protein levels resulting in increased cell motility. Gene
      expression profiling of CRABP-II-expressing cell lines uncovered increased
      expression of the HuB (Hel N1) gene. Hu proteins have been implicated in
      regulating the stability of MycN mRNA and other mRNAs by binding to their 3'
      untranslated regions. We did not, however, observe any change in MycN mRNA
      stability or protein half-life in response to CRABP-II expression. In contrast,
      de novo MycN protein synthesis was increased in CRABP-II-expressing neuroblastoma
      cells, thereby suggesting an autoregulatory loop that might exacerbate the
      effects of MycN gene amplification and affect the clinical outcome. Our findings
      also suggest that CRABP-II may be a potential therapeutic target for
      neuroblastoma.

PMID- 16912188
TI  - Deficiency in the repair of DNA damage by homologous recombination and
      sensitivity to poly(ADP-ribose) polymerase inhibition.
AB  - Deficiency in either of the breast cancer susceptibility proteins BRCA1 or BRCA2
      induces profound cellular sensitivity to the inhibition of poly(ADP-ribose)
      polymerase (PARP) activity. We hypothesized that the critical role of BRCA1 and
      BRCA2 in the repair of double-strand breaks by homologous recombination (HR) was
      the underlying reason for this sensitivity. Here, we examine the effects of
      deficiency of several proteins involved in HR on sensitivity to PARP inhibition.
      We show that deficiency of RAD51, RAD54, DSS1, RPA1, NBS1, ATR, ATM, CHK1, CHK2,
      FANCD2, FANCA, or FANCC induces such sensitivity. This suggests that BRCA
      deficient cells are, at least in part, sensitive to PARP inhibition because of HR
      deficiency. These results indicate that PARP inhibition might be a useful
      therapeutic strategy not only for the treatment of BRCA mutation-associated
      tumors but also for the treatment of a wider range of tumors bearing a variety of
      deficiencies in the HR pathway or displaying properties of 'BRCAness.'

PMID- 16912189
TI  - Tip60 protein isoforms and altered function in skin and tumors that overexpress
      ornithine decarboxylase.
AB  - Elevated expression of ornithine decarboxylase (ODC) and increased synthesis of
      polyamines are hallmarks of epithelial tumorigenesis. The skin and tumors of
      K6/ODC and ODC/Ras transgenic mice, in which overexpression of ODC has been
      targeted to hair follicles, were found to exhibit intrinsically high histone
      acetyltransferase (HAT) activity. We identified Tip60 as a candidate enzyme for
      contributing significantly to this abnormally high HAT activity. Compared with
      normal littermate controls, the levels of Tip60 protein and an alternative splice
      variant Tip53 were found to be greater in K6/ODC mouse skin. Furthermore, skin
      tumors that spontaneously develop in ODC/Ras bigenic mice typically have
      substantially more Tip60 protein than adjacent non-tumor-bearing skin and exhibit
      a unique pattern of Tip60 size variants and chemically modified protein isoforms.
      Steady-state Tip60 and Tip53 mRNA levels were not affected in ODC-overexpressing
      skin and tumors, implying novel posttranscriptional regulation by polyamines.
      Given the diverse roles of Tip60, the overabundance of Tip60 protein is predicted
      to have biological consequences. Compared with normal littermate skin, we
      detected altered association of Tip60 with E2F1 and a subset of newly identified
      Tip60-interacting transcription factors in ODC transgenic mouse skin and tumors.
      E2F1 was shown to be bound in greater amounts to up-regulated target genes in ODC
      overexpressing skin. Thus, up-regulation of Tip60 protein, influencing the
      expression of Tip60-regulated genes, could play a contributing role in polyamine
      mediated tumor promotion. (

PMID- 16912190
TI  - Discoidin domain receptor 1 receptor tyrosine kinase induces cyclooxygenase-2 and
      promotes chemoresistance through nuclear factor-kappaB pathway activation.
AB  - Discoidin domain receptor 1 (DDR1) is a receptor tyrosine kinase activated by
      various types of collagens and is known to play a role in cell attachment,
      migration, survival, and proliferation. However, little is known about the
      molecular mechanism(s) underlying the role of DDR1 in cancer. We report here that
      DDR1 induces cyclooxygenase-2 (Cox-2) expression resulting in enhanced
      chemoresistance. Depletion of DDR1-mediated Cox-2 induction using short hairpin
      RNA (shRNA) results in increased chemosensitivity. We also show that DDR1
      activates the nuclear factor-kappaB (NF-kappaB) pathway and blocking this
      activation by an I kappaB superrepressor mutant results in the ablation of DDR1
      induced Cox-2, leading to enhanced chemosensitivity, indicating that DDR1
      mediated Cox-2 induction is NF-kappaB dependent. We identify the upstream
      activating kinases of the NF-kappaB pathway, IKK beta and IKK gamma, as essential
      for DDR1-mediated NF-kappaB activation, whereas IKK alpha seems to be
      dispensable. Finally, shRNA-mediated inhibition of DDR1 expression significantly
      enhanced chemosensitivity to genotoxic drugs in breast cancer cells. Thus, DDR1
      signaling provides a novel target for therapeutic intervention with the
      prosurvival/antiapoptotic machinery of tumor cells.

PMID- 16912191
TI  - Role of nongenomic activation of phosphatidylinositol 3-kinase/Akt and mitogen
      activated protein kinase/extracellular signal-regulated kinase
      kinase/extracellular signal-regulated kinase 1/2 pathways in 1,25D3-mediated
      apoptosis in squamous cell carcinoma cells.
AB  - Vitamin D is a steroid hormone that regulates calcium homeostasis and bone
      metabolism. The active form of vitamin D [1 alpha,25-dihydroxyvitamin D(3)
      (1,25D3)] acts through both genomic and nongenomic pathways. 1,25D3 has antitumor
      effects in a variety of cancers, including colorectal, prostate, breast, ovarian,
      and skin cancers. 1,25D3 exerts growth-inhibitory effects in cancer cells through
      the induction of apoptosis, cell cycle arrest, and differentiation. The
      mechanisms regulating 1,25D3-induced apoptosis remain unclear. We investigated
      the role of nongenomic signaling in 1,25D3-mediated apoptosis in squamous cell
      carcinoma (SCC) cells. 1,25D3 induced rapid and sustained activation of
      phosphatidylinositol 3-kinase/Akt and mitogen-activated protein
      kinase/extracellular signal-regulated kinase (ERK) 1/2 pathways in SCC cells.
      These effects were nongenomic: they occurred rapidly and were not inhibited by
      cycloheximide or actinomycin D. To examine whether the nongenomic activation of
      Akt and ERK1/2 plays a role in 1,25D3-mediated apoptosis, the expression of Akt
      or ERK1/2 was reduced by small interfering RNA (siRNA). siRNA-Akt significantly
      enhanced 1,25D3-induced apoptosis as indicated by increased levels of Annexin V
      positive cells and increased sub-G(1) population and DNA fragmentation. In
      contrast, siRNA-ERK1/2 had no effects on 1,25D3-induced apoptosis. In addition,
      siRNA-Akt transfection followed by 1,25D3 treatment induced apoptosis much sooner
      than 1,25D3 alone. siRNA-Akt and 1,25D3 induced caspase-10 activation, suppressed
      the expression of c-IAP1 and XIAP, and promoted 1,25D3-induced caspase-3
      activation. These results support a link between 1,25D3-induced nongenomic
      signaling and apoptosis. 1,25D3 induces the activation of phosphatidylinositol 3
      kinase/Akt, which suppresses 1,25D3-mediated apoptosis and prolongs the survival
      of SCC cells.

PMID- 16912192
TI  - Inhibition of phosphatidylinositol 3-kinase destabilizes Mycn protein and blocks
      malignant progression in neuroblastoma.
AB  - Amplification of MYCN occurs commonly in neuroblastoma. We report that
      phosphatidylinositol 3-kinase (PI3K) inhibition in murine neuroblastoma (driven
      by a tyrosine hydroxylase-MYCN transgene) led to decreased tumor mass and
      decreased levels of Mycn protein without affecting levels of MYCN mRNA.
      Consistent with these observations, PI3K inhibition in MYCN-amplified human
      neuroblastoma cell lines resulted in decreased levels of Mycn protein without
      affecting levels of MYCN mRNA and caused decreased proliferation and increased
      apoptosis. To clarify the importance of Mycn as a target of broad-spectrum PI3K
      inhibitors, we transduced wild-type N-myc and N-myc mutants lacking glycogen
      synthase kinase 3beta phosphorylation sites into human neuroblastoma cells with
      no endogenous expression of myc. In contrast to wild-type N-myc, the
      phosphorylation-defective mutant proteins were stabilized and were resistant to
      the antiproliferative effects of PI3K inhibition. Our results show the importance
      of Mycn as a therapeutic target in established tumors in vivo, offer a
      mechanistic rationale to test PI3K inhibitors in MYCN-amplified neuroblastoma,
      and represent a therapeutic approach applicable to a broad range of cancers in
      which transcription factors are stabilized through a PI3K-dependent mechanism.

PMID- 16912193
TI  - Frequent alterations in the expression of serine/threonine kinases in human
      cancers.
AB  - Protein kinases constitute a large family of regulatory enzymes involved in the
      homeostasis of virtually every cellular process. Subversion of protein kinases
      has been frequently implicated in malignant transformation. Within the family,
      serine/threonine kinases (STK) have received comparatively lesser attention, vis
      a-vis tyrosine kinases, in terms of their involvement in human cancers. Here, we
      report a large-scale screening of 125 STK, selected to represent all major
      subgroups within the subfamily, on nine different types of tumors ( approximately
      200 patients), by using in situ hybridization on tissue microarrays. Twenty-one
      STK displayed altered levels of transcripts in tumors, frequently with a clear
      tumor type-specific dimension. We identified three patterns of alterations in
      tumors: (a) overexpression in the absence of expression in the normal tissues (10
      kinases), (b) overexpression in the presence of expression by normal tissues (8
      kinases), and (c) underexpression (3 kinases). Selected members of the three
      classes were subjected to in-depth analysis on larger case collections and showed
      significant correlations between their altered expression and biological and/or
      clinical variables. Our findings suggest that alteration in the expression of STK
      is a relatively frequent occurrence in human tumors. Among the overexpressed
      kinases, 10 were undetectable in normal controls and are therefore ideal
      candidates for further validation as potential targets of molecular cancer
      therapy.

PMID- 16912194
TI  - Cross-talk between nucleotide excision and homologous recombination DNA repair
      pathways in the mechanism of action of antitumor trabectedin.
AB  - Trabectedin (Yondelis) is a potent antitumor drug that has the unique
      characteristic of killing cells by poisoning the DNA nucleotide excision repair
      (NER) machinery. The basis for the NER-dependent toxicity has not yet been
      elucidated but it has been proposed as the major determinant for the drug's
      cytotoxicity. To study the in vivo mode of action of trabectedin and to explore
      the role of NER in its cytotoxicity, we used the fission yeast
      Schizosaccharomyces pombe as a model system. Treatment of S. pombe wild-type
      cells with trabectedin led to cell cycle delay and activation of the DNA damage
      checkpoint, indicating that the drug causes DNA damage in vivo. DNA damage
      induced by the drug is mostly caused by the NER protein, Rad13 (the fission yeast
      orthologue to human XPG), and is mainly repaired by homologous recombination. By
      constructing different rad13 mutants, we show that the DNA damage induced by
      trabectedin depends on a 46-amino acid region of Rad13 that is homologous to a
      DNA-binding region of human nuclease FEN-1. More specifically, an arginine
      residue in Rad13 (Arg961), conserved in FEN1 (Arg314), was found to be crucial
      for the drug's cytotoxicity. These results lead us to propose a model for the
      action of trabectedin in eukaryotic cells in which the formation of a Rad13/DNA
      trabectedin ternary complex, stabilized by Arg961, results in cell death.

PMID- 16912195
TI  - Kinetic analysis of epidermal growth factor receptor somatic mutant proteins
      shows increased sensitivity to the epidermal growth factor receptor tyrosine
      kinase inhibitor, erlotinib.
AB  - We show that two commonly occurring epidermal growth factor receptor (EGFR)
      somatic mutations, L858R and an in-frame deletion mutant, Del(746-750), exhibit
      distinct enzymatic properties relative to wild-type EGFR and are differentially
      sensitive to erlotinib. Kinetic analysis of the purified intracellular domains of
      EGFR L858R and EGFR Del(746-750) reveals that both mutants are active but exhibit
      a higher K(M) for ATP and a lower K(i) for erlotinib relative to wild-type
      receptor. When expressed in NR6 cells, a cell line that does not express EGFR or
      other ErbB receptors, both mutations are ligand dependent for receptor
      activation, can activate downstream EGFR signaling pathways, and promote cell
      cycle progression. As expected from the kinetic analysis, the EGFR Del(746-752)
      is more sensitive to erlotinib inhibition than the EGFR L858R mutant. Further
      characterization shows that these mutations promote ligand-dependent and
      anchorage-independent growth, and cells harboring these mutant receptors form
      tumors in immunocompromised mice. Analysis of tumor lysates reveals that the
      tumorigenicity of the mutant EGFR cell lines may be due to a differential pattern
      of mutant EGFR autophosphorylation as compared with wild-type receptor.
      Significant inhibition of tumor growth, in mice harboring wild-type EGFR
      receptors, is only observed at doses of erlotinib approaching the maximum
      tolerated dose for the mouse. In contrast, the growth of mutant tumors is
      inhibited by erlotinib treatment at approximately one third the maximum tolerated
      dose. These findings suggest that EGFR somatic mutations directly influence both
      erlotinib sensitivity and cellular transformation.

PMID- 16912196
TI  - Zebrafish as a "biosensor"? Effects of ionizing radiation and amifostine on
      embryonic viability and development.
AB  - The zebrafish (Danio rerio) has emerged as a popular vertebrate model system for
      cancer and treatment-related research. Benefits include ease of care, rapid
      development, optical clarity of embryos, which allows visualization of major
      organ systems, and opportunities for genetic manipulation. However, specific
      parameters of radiation sensitivity have not been systematically documented. We
      investigated the effects of radiation and a radiomodifier on zebrafish viability
      and embryonic development. Embryos were exposed to gamma-radiation (5, 10, or 20
      Gy) at sequential times postfertilization and serially assessed for viability and
      morphologic abnormalities. As expected, lethality and morphologic perturbations
      were more pronounced earlier in embryogenesis and with higher radiation doses and
      were partially reversed by amifostine. The effects of radiation and concurrent
      treatment with amifostine on the developmental organization of the eye and brain
      were striking. Radiation resulted in hypocellularity and disorganization of the
      cellular layers of the retina, effects partially reversed by amifostine, as well
      as lens opacification. Radiation strikingly reduced the volume of brain, but the
      volume loss was substantially blocked by amifostine. Increased terminal
      deoxyribonucleotidyl transferase-mediated dUTP nick end labeling signal was noted
      in both the irradiated eye and brain, but reduced by amifostine. Finally,
      irradiating embryos resulted in caspase activation detectable in 96-well
      microplates, which was proportional to the number of embryos and radiation dose;
      the degree of activation was markedly reduced by amifostine. These results
      together suggest the power and versatility of the zebrafish in assessing the
      effects of radiation and radiomodifiers on organ and tissue development.

PMID- 16912197
TI  - BiP/GRP78 is an intracellular target for MDA-7/IL-24 induction of cancer-specific
      apoptosis.
AB  - Melanoma differentiation-associated gene-7/interleukin-24 (mda-7/IL-24) is a
      unique member of the IL-10 gene family that induces cancer-selective growth
      suppression and apoptosis in a wide spectrum of human cancers in cell culture and
      animal models. Additionally, recent clinical trials confirm safety and document
      significant clinical activity of mda-7/IL-24 in patients with diverse solid
      cancers and melanomas. Despite intensive study the molecular basis of tumor-cell
      selectivity of mda-7/IL-24 is not well characterized. Using deletion analysis, a
      specific mutant of MDA-7/IL-24, M4, consisting of amino acids 104 to 206, is
      described that retains the cancer-specific growth-suppressive and apoptosis
      inducing properties of the full-length protein. Employing rationally designed
      mutational analysis, we show that MDA-7/IL-24 and M4 physically interact with
      BiP/GRP78 through their C and F helices, localize in the endoplasmic reticulum,
      and activate p38 MAPK and GADD gene expression, culminating in cancer-selective
      apoptosis. These studies provide novel mechanistic insights into the
      discriminating antitumor activity of MDA-7/IL-24 by elucidating BiP/GRP78 as a
      defined intracellular target of action and present an unparalleled opportunity to
      develop improved therapeutic versions of this cancer-specific apoptosis-inducing
      cytokine.

PMID- 16912198
TI  - Taxotere-induced inhibition of human endothelial cell migration is a result of
      heat shock protein 90 degradation.
AB  - In addition to effects on tumor cell proliferation and apoptosis, microtubule
      binding agents are potent inhibitors of angiogenesis. The cancer chemotherapeutic
      drug Taxotere (docetaxel) inhibited vascular endothelial growth factor (VEGF)
      induced human umbilical vein endothelial cell (HUVEC) migration in vitro at
      concentrations substantially lower than required to cause cell cycle arrest or
      apoptosis. Here, we show that Taxotere caused the ubiquitination and subsequent
      proteasomal degradation of heat shock protein 90 (Hsp90) in HUVEC. This prevented
      signaling from the focal adhesions and VEGF receptors and inhibited integrin
      activation. Taxotere prevented the VEGF-induced phosphorylation of focal adhesion
      kinase, Akt, and endothelial nitric oxide synthase (eNOS), all of which are Hsp90
      client proteins. Taxotere completely blocked the VEGF-induced increase in eNOS
      activity, and the addition of a NO donor reversed the inhibitory effect of
      Taxotere on VEGF-induced migration. A similar reversal occurred with a
      proteasomal inhibitor of Hsp90 degradation. Furthermore, overexpression of Hsp90
      rescued HUVEC from the inhibition of VEGF-induced migration by Taxotere. Previous
      studies have suggested that tubulin is also a client protein of Hsp90, and
      immunocytochemical analysis showed that Taxotere caused the dissociation of Hsp90
      from tubulin. We suggest that uncomplexed Hsp90 is more susceptible to
      ubiquitination and subsequent proteasomal degradation than the bound form.
      Although inhibitors of Hsp90 are currently under clinical investigation as
      antitumor agents, this seems to be the first account of a drug that reduces Hsp90
      function by enhancing its proteasomal degradation. Further, the loss of Hsp90 and
      the inactivation of Hsp90 client proteins are previously undescribed actions of
      Taxotere that may contribute to its antiangiogenic activity.

PMID- 16912200
TI  - Gene expression profiles identify epithelial-to-mesenchymal transition and
      activation of nuclear factor-kappaB signaling as characteristics of a high-risk
      head and neck squamous cell carcinoma.
AB  - Gene expression signatures generated from DNA microarray analyses have shown
      promise as predictive biomarkers of clinical outcome. In this study, we
      determined a high-risk signature for disease recurrence using formalin-fixed head
      and neck squamous cell carcinoma (HNSCC) tumors and compared the results with an
      independent data set obtained from fresh frozen tumors. We also showed that genes
      involved in epithelial-to-mesenchymal transition (EMT) and nuclear factor-kappaB
      (NF-kappaB) signaling deregulation are the most prominent molecular
      characteristics of the high-risk tumors. Gene expression was determined in 40
      samples, including 34 formalin-fixed tissues and 6 matched frozen tissues, from
      29 HNSCC patients. A 75-gene list predictive of disease recurrence was determined
      by training on the formalin-fixed tumor data set and tested on data from the
      independent frozen tumor set from 60 HNSCC patients. The difference in recurrence
      free survival (RFS) between the high-risk versus low-risk groups in the training
      and test sets was statistically significant (P = 0.002 and 0.03, respectively,
      log-rank test). In addition, the gene expression data was interrogated using Gene
      Set Enrichment Analysis to determine biological significance. The most
      significant sets of genes enriched in the high-risk tumors were genes involving
      EMT, NF-kappaB activation, and cell adhesion. In conclusion, global gene
      expression analysis is feasible using formalin-fixed tissue. The 75-gene list can
      be used as a prognostic biomarker of recurrence, and our data suggest that the
      molecular determinants of EMT and NF-kappaB activation can be targeted as the
      novel therapy in the identified high-risk patients.

PMID- 16912199
TI  - Targeting mitogen-activated protein kinase/extracellular signal-regulated kinase
      kinase in the mutant (V600E) B-Raf signaling cascade effectively inhibits
      melanoma lung metastases.
AB  - Malignant melanoma has a high propensity for metastatic spread, making it the
      most deadly form of skin cancer. B-RAF has been identified as the most mutated
      gene in these invasive cells and therefore an attractive therapeutic target.
      However, for uncertain reasons, chemotherapy inhibiting B-Raf has not been
      clinically effective. This has raised questions whether this pathway is important
      in melanoma metastasis or whether targeting a protein other than B-Raf in the
      signaling cascade could more effectively inhibit this pathway to reduce lung
      metastases. Here, we investigated the role played by (V600E)B-Raf in melanoma
      metastasis and showed that targeting this signaling cascade significantly reduces
      lung metastases. Small interfering RNA (siRNA)-mediated inhibition was used in
      mice to reduce expression (activity) of each member of the signaling cascade and
      effects on metastasis development were measured. Targeting any member of the
      signaling cascade reduced metastasis but inhibition of mitogen-activated protein
      kinase/extracellular signal-regulated kinase kinase (Mek) 1 and Mek 2 almost
      completely prevented lung tumor development. Mechanistically, metastatic
      inhibition was mediated through reduction of melanoma cell extravasation through
      the endothelium and decreased proliferative capacity. Targeting B-Raf with the
      pharmacologic inhibitor BAY 43-9006, which was found ineffective in clinical
      trials and seems to act primarily as an angiogenesis inhibitor, did not decrease
      metastasis, whereas inhibition of Mek using U0126 decreased cellular
      proliferative capacity, thereby effectively reducing number and size of lung
      metastases. In summary, this study provides a mechanistic basis for targeting Mek
      and not B-Raf in the mutant (V600E)B-Raf signaling cascade to inhibit melanoma
      metastases.

PMID- 16912201
TI  - Cyclin-dependent kinase 2 functions in normal DNA repair and is a therapeutic
      target in BRCA1-deficient cancers.
AB  - Abnormal regulation of progression from G(1) to S phase of the cell cycle by
      altered activity of cyclin-dependent kinases (CDKs) is a hallmark of cancer.
      However, inhibition of CDKs, particularly CDK2, has not shown selective activity
      against most cancer cells because the kinase seems to be redundant in control of
      cell cycle progression. Here, we show a novel role in the DNA damage response and
      application of CDK inhibitors in checkpoint-deficient cells. CDK2(-/-) mouse
      fibroblasts and small interfering RNA--mediated or small-molecule--mediated CDK2
      inhibition in MCF7 or U2OS cells lead to delayed damage signaling through Chk1,
      p53, and Rad51. This coincided with reduced DNA repair using the single-cell
      comet assay and defects observed in both homologous recombination and
      nonhomologous end-joining in cell-based assays. Furthermore, tumor cells lacking
      cancer predisposition genes BRCA1 or ATM are 2- to 4-fold more sensitive to CDK
      inhibitors. These data suggest that inhibitors of CDK2 can be applied to
      selectively enhance responses of cancer cells to DNA-damaging agents, such as
      cytotoxic chemotherapy and radiotherapy. Moreover, inhibitors of CDKs may be
      useful therapeutics in cancers with defects in DNA repair, such as mutations in
      the familial breast cancer gene BRCA1.

PMID- 16912202
TI  - The anti-CD25 monoclonal antibody 7G7/B6, armed with the alpha-emitter 211At,
      provides effective radioimmunotherapy for a murine model of leukemia.
AB  - Radioimmunotherapy of cancer with radiolabeled antibodies has shown promise.
      alpha-Particles are very attractive for cancer therapy, especially for isolated
      malignant cells, as is observed in leukemia, because of their high linear energy
      transfer and short effective path length. We evaluated an anti-CD25 [interleukin
      2 receptor alpha (IL-2R alpha)] monoclonal antibody, 7G7/B6, armed with (211)At
      as a potential radioimmunotherapeutic agent for CD25-expressing leukemias and
      lymphomas. Therapeutic studies were done in severe combined
      immunodeficient/nonobese diabetic mice bearing the karpas299 leukemia and in nude
      mice bearing the SUDHL-1 lymphoma. The results from a pharmacokinetic study
      showed that the clearance of (211)At-7G7/B6 from the circulation was virtually
      identical to (125)I-7G7/B6. The biodistributions of (211)At-7G7/B6 and (125)I
      7G7/B6 were also similar with the exception of a higher stomach uptake of
      radioactivity with (211)At-7G7/B6. Therapy using 15 microCi of (211)At-7G7/B6
      prolonged survival of the karpas299 leukemia-bearing mice significantly when
      compared with untreated mice and mice treated with (211)At-11F11, a radiolabeled
      nonspecific control antibody (P < 0.01). All of the mice in the control and
      (211)At-11F11 groups died by day 46 whereas >70% of the mice in the (211)At
      7G7/B6 group still survived at that time. In summary, (211)At-7G7/B6 could serve
      as an effective therapeutic agent for patients with CD25-expressing leukemias.

PMID- 16912203
TI  - Assessment of endostatin gene therapy for familial adenomatous polyposis-related
      desmoid tumors.
AB  - Constitutive activation of the Wnt signaling pathway is a hallmark of many
      cancers, including familial adenomatous polyposis (FAP)-related desmoid tumors.
      Endostatin is a well-known antiangiogenic protein that has been described
      recently as a potential inhibitor of this signaling pathway. Here, we show that
      endostatin directly induces apoptosis and inhibits the Wnt signaling pathway in
      colorectal cancer cell lines bearing mutations on the adenomatous polyposis coli
      (APC) gene as a model of FAP-related malignant cells. We then explore the
      relationship between apoptosis and inhibition of this pathway and show that they
      are not correlated. These results seem to contradict a well-recognized study,
      showing that reintroduction of the APC cDNA in APC-deficient cells leads to
      apoptosis. To reconcile our conclusions with the literature, we further show that
      a truncated fragment of APC capable of inhibiting the Wnt signaling pathway in
      SW480 cells is incapable of inducing apoptosis in these cells, confirming that
      APC-mediated apoptosis is uncoupled to the inhibition of the Wnt signaling
      pathway. Finally, we show that endostatin directly induces cell death on primary
      FAP-related desmoid tumor cells in culture. This phenomenon is also independent
      of the inhibition of the Wnt signaling pathway. Considering the current lack of
      effective treatment against desmoid tumors, we advocate that endostatin gene
      therapy represents an attractive new therapeutic approach for this disease.

PMID- 16912204
TI  - Different lineages of P1A-expressing cancer cells use divergent modes of immune
      evasion for T-cell adoptive therapy.
AB  - Tumor evasion of T-cell immunity remains a significant obstacle to adoptive T
      cell therapy. It is unknown whether the mode of immune evasion is dictated by the
      cancer cells or by the tumor antigens. Taking advantage of the fact that multiple
      lineages of tumor cells share the tumor antigen P1A, we adoptively transferred
      transgenic T cells specific for P1A (P1CTL) into mice with established P1A
      expressing tumors, including mastocytoma P815, plasmocytoma J558, and
      fibrosarcoma Meth A. Although P1CTL conferred partial protection, tumors recurred
      in almost all mice. Analysis of the status of the tumor antigen revealed that all
      J558 tumors underwent antigenic drift whereas all P815 tumors experienced
      antigenic loss. Interestingly, although Meth A cells are capable of both
      antigenic loss and antigenic drift, the majority of recurrent Meth A tumors
      retained P1A antigen. The ability of Meth A to induce apoptosis of P1CTL in vivo
      alleviated the need for antigenic drift and antigenic loss. Our data showed that,
      in spite of their shared tumor antigen, different lineages of cancer cells use
      different mechanisms to evade T-cell therapy.

PMID- 16912205
TI  - Neutrophil granulocytes are required for effective Bacillus Calmette-Guerin
      immunotherapy of bladder cancer and orchestrate local immune responses.
AB  - The role of polymorphonuclear neutrophil granulocytes (PMN) in antitumoral immune
      responses displays a striking dichotomy. Under inflammatory conditions, PMN may
      promote tumor growth and progression. In contrast, especially in the context of
      therapeutic interventions, PMN can exert important antitumor functions. However,
      until now, the mechanisms of PMN-mediated activation of tumor immunity are poorly
      defined. Based on a murine model of Bacillus Calmette-Guerin (BCG) immunotherapy
      of bladder cancer, we provide evidence for a novel immunoregulatory role of this
      leukocyte subset. PMN immigrate into the bladder after intravesical BCG
      instillation and depletion of PMN from tumor-bearing mice completely abrogated
      antitumor efficacy of BCG. PMN stimulated with BCG in vitro as well as PMN
      isolated from the urine of BCG-treated patients were a major source of the
      chemokines interleukin-8, growth-related oncogene-alpha, macrophage inflammatory
      protein-1 alpha and of the inflammatory cytokine migration inhibitory factor. In
      vitro, BCG-stimulated PMN indirectly induced T-cell chemotaxis via the accessory
      function of activated monocytes. In vivo, depletion of PMN from BCG-treated mice
      significantly impaired CD4(+) T-cell trafficking to the bladder. These data show
      that PMN direct the migration of effector cells to the bladder and by this means
      are indispensable for effective tumor immunotherapy. Thus, our findings provide
      evidence for a novel early immunoregulatory role of these innate immune cells in
      local antitumor immunity.

PMID- 16912206
TI  - The shaping of a polyvalent and highly individual T-cell repertoire in the bone
      marrow of breast cancer patients.
AB  - We analyzed the T-cell repertoires from the bone marrow of 39 primary operated
      breast cancer patients and 11 healthy female donors for the presence and
      frequencies of spontaneously induced effector/memory T lymphocytes with peptide
      HLA-A2-restricted reactivity against 10 breast tumor-associated antigens (TAA)
      and 3 normal breast tissue-associated antigens by short-term IFN-gamma enzyme
      linked immunospot (ELISpot) analysis. Sixty-seven percent of the patients
      recognized TAAs with a mean frequency of 144 TAA reactive cells per 10(6) T
      cells. These patients recognized simultaneously an average of 47% of the tested
      TAAs. The T-cell repertoire was highly polyvalent and exhibited pronounced
      interindividual differences in the pattern of TAAs recognized by each patient.
      Strong differences of reactivity were noticed between TAAs, ranging from 100%
      recognition of prostate-specific antigen(p141-149) to only 25% recognition of
      MUC1(p12-20) or Her-2/neu(p369-377). In comparison with TAAs, reactivity to
      normal breast tissue-associated antigens was lower with respect to the
      proportions of responding patients (30%) and recognized antigens (27%), with a
      mean frequency of only 85/10(6) T cells. Healthy individuals also contained TAA
      reactive T cells but this repertoire was more restricted and the frequencies were
      in the same range as T cells reacting to normal breast tissue-associated
      antigens. Our data show a highly individual T-cell repertoire for recognition of
      TAAs in breast cancer patients. This has potential relevance for T-cell immune
      diagnostics, for tumor vaccine design, and for predicting immune responsiveness.

PMID- 16912207
TI  - Mechanisms of tumor regression and resistance to estrogen deprivation and
      fulvestrant in a model of estrogen receptor-positive, HER-2/neu-positive breast
      cancer.
AB  - HER-2/neu in breast cancer is associated with tamoxifen resistance, but little
      data exist on its interaction with estrogen deprivation or fulvestrant. Here, we
      used an in vivo xenograft model of estrogen receptor (ER)-positive breast cancer
      with HER-2/neu overexpression (MCF7/HER-2/neu-18) to investigate mechanisms of
      growth inhibition and treatment resistance. MCF7/HER-2/neu-18 tumors were growth
      inhibited by estrogen deprivation and with fulvestrant, but resistance developed
      in 2 to 3 months. Inhibited tumors had reductions in ER, insulin-like growth
      factor-I receptor (IGF-IR), phosphorylated HER-2/neu (p-HER-2/neu), and
      phosphorylated p42/44 mitogen-activated protein kinase (p-MAPK). p27 was
      increased especially in tumors sensitive to estrogen deprivation. Tumors with
      acquired resistance to these therapies had complete loss of ER, increased p-HER
      2/neu, increased p-MAPK, and reduced p27. In contrast, IGF-IR and phosphorylated
      AKT (p-AKT) levels were markedly reduced in these resistant tumors. The epidermal
      growth factor receptor (EGFR) tyrosine kinase inhibitor gefitinib, which can
      block EGFR/HER-2/neu signaling, significantly delayed the emergence of resistance
      to both estrogen deprivation and fulvestrant. Levels of p-MAPK and p-AKT
      decreased with gefitinib, whereas high ER levels were restored. Eventually,
      however, tumors progressed in mice treated with gefitinib combined with estrogen
      deprivation or fulvestrant accompanied again by loss of ER and IGF-IR, increased
      p-HER-2/neu, high p-MAPK, and now increased p-AKT. Thus, estrogen deprivation and
      fulvestrant can effectively inhibit HER-2/neu-overexpressing tumors but
      resistance develops quickly. EGFR/HER-2/neu inhibitors can delay resistance, but
      reactivation of HER-2/neu and signaling through AKT leads to tumor regrowth.
      Combining endocrine therapy with EGFR/HER-2/neu inhibitors should be tested in
      clinical breast cancer, but a more complete blockade of EGFR/HER-2/neu may be
      optimal.

PMID- 16912208
TI  - Spontaneous fusion with, and transformation of mouse stroma by, malignant human
      breast cancer epithelium.
AB  - Adenocarcinoma cells from the pleural effusion of a patient with breast cancer
      were injected into the mammary glands of nude mice and grown into solid tumors. A
      cell line derived from these tumors expressed alpha-smooth muscle actin but not
      human cytokeratin 7, indicating "activated" stroma of mouse origin. Cells in
      mitosis exhibited mainly polyploid mouse karyotypes, but 30% had mixed mouse and
      human chromosomes, among which 8% carried mouse/human translocations. Nuclei of
      interphase cells were 64% hybrid. Hybrid mouse/human nuclei were also detected in
      the primary xenograft. Thus, synkaryons formed in the solid tumor by spontaneous
      fusion between the malignant human epithelium and the surrounding normal host
      mouse stroma. The transformed stroma-derived cells are tumorigenic with
      histopathologic features of malignancy, suggesting a new mechanism for tumor
      progression.

PMID- 16912209
TI  - Sequence variants in cell cycle control pathway, X-ray exposure, and lung cancer
      risk: a multicenter case-control study in Central Europe.
AB  - Exposure to ionizing radiation (IR) results in various types of DNA damage and is
      a suspected cause of lung cancer. An essential cellular machinery against DNA
      damage is cell cycle control, which is regulated by several genes, including
      TP53, CCND1, and CDKN2A. Therefore, we hypothesized that the genetic variants in
      these three genes influence the predisposition of lung cancer (i.e., CCND1 G870A,
      CDKN2A Ala(148)Thr, TP53 Arg(72)Pro, and 16-bp repeat in intron 3) and that the
      effect of X-ray on lung cancer risk can be modified by the presence of these
      genetic variations. The study was conducted in 15 centers in 6 countries of
      Central Europe between 1998 and 2002. A total of 2,238 cases and 2,289 controls
      were recruited and provided DNA samples. Cases with positive family history were
      analyzed separately. The joint effect of X-ray and previous risk genotypes was
      assessed, and modification by sequence variants on X-ray dose-response
      relationship with lung cancer risk was evaluated. We found an overall effect of
      TP53 intron 3 16-bp repeats [odds ratio (OR), 1.99; 95% confidence interval (95%
      CI), 1.27-3.13], which was stronger among cases with family history of lung
      cancer (OR, 2.98; 95% CI, 1.29-6.87). In addition, our results suggested an
      interaction that was greater than multiplicativity between TP53 intron 3 16-bp
      repeats and multiple X-ray exposures (interaction OR, 5.69; 95% CI, 1.33-24.3).
      We did not observe a main effect of CCND1 G870A polymorphism; however, the dose
      response relationship between lung cancer risk and X-ray exposures was modified
      by CCND1 genotype with no risk from X-ray exposures among subjects who carried
      G/G genotype, intermediate risk [trend OR for X-ray, 1.16; 95% CI, 1.05-1.27)
      among subjects with G/A genotype, and highest risk [trend OR for X-ray, 1.29; 95%
      CI, 1.12-1.49) among subjects with A/A genotype. Sequence variants in cell cycle
      control pathway may increase the risk of lung cancer and modify the risk
      conferred by multiple X-ray exposures. However, a definite conclusion can only be
      drawn on replication by different studies among individuals who are highly
      exposed to IR.

PMID- 16912210
TI  - Joint effects of germ-line p53 mutation and sex on cancer risk in Li-Fraumeni
      syndrome.
AB  - Germ-line p53 mutations have been identified in most families with Li-Fraumeni
      syndrome (LFS). For germ-line p53 mutation carriers, there is considerable
      variability with respect to age of cancer onset and tumor type, suggesting that
      additional genetic effects influence the clinical severity and tumor spectrum. To
      identify factors that might contribute to the observed heterogeneity in time to
      onset, we used segregation analysis to analyze the joint effects of germ-line p53
      mutations and risk modifier(s) on cancer incidence. We studied 159 kindreds,
      ascertained through probands who had been diagnosed with childhood soft-tissue
      sarcoma before 16 years of age, survived >3 years after diagnosis, and treated at
      The University of Texas M.D. Anderson Cancer Center (Houston, TX) from 1944 to
      1975. This unique cohort has been followed systematically for >20 years and has
      had germ-line p53 mutation testing in probands and extended family members. The
      analyses revealed that germ-line p53 mutations and sex had significant effects on
      cancer risk: men with p53 mutations had 151-fold higher odds of developing cancer
      than did those without mutations [95% confidence interval (95% CI), 60-380], and
      women with p53 mutations had 1,075-fold higher odds than did those without
      mutations (95% CI, 358-3,229) and 7.1-fold higher odds of having cancer than did
      men with mutations (95% CI, 2.5-20.3). These findings provide quantitative cancer
      risk assessments for LFS families.

PMID- 16912211
TI  - Inhibition of 7,12-dimethylbenz(a)anthracene-induced skin tumorigenesis in
      C57BL/6 mice by sulforaphane is mediated by nuclear factor E2-related factor 2.
AB  - Sulforaphane, a dietary isothiocyanate, possesses potent chemopreventive effects
      through the induction of cellular detoxifying/antioxidant enzymes via the
      transcription factor nuclear factor E2-related factor 2 (Nrf2). To investigate
      carcinogenesis mechanisms related to the regulation of Nrf2, we examined the
      tumor incidence and tumor numbers per mouse in Nrf2 wild-type (+/+) and Nrf2
      knockout (-/-) mice. 7,12-Dimethylbenz(a)anthracene/12-O-tetradecanoylphorbol-13
      acetate treatments resulted in an increase in the incidence of skin tumors and
      tumor numbers per mouse in both genotypes; however, both indices were markedly
      higher in Nrf2(-/-) mice as compared with Nrf2(+/+) mice. Western blot analysis
      revealed that Nrf2 as well as heme oxygenase-1, a protein regulated by Nrf2 were
      not expressed in skin tumors from mice of either genotype, whereas expression of
      heme oxygenase-1 in Nrf2(+/+) mice was much higher than that in Nrf2(-/-) mice in
      nontumor skin samples. Next, we examined the chemopreventive efficacy of
      sulforaphane in mice with both genotypes. Topical application of 100 nmol of
      sulforaphane once a day for 14 days prior to 7,12-dimethylbenz(a)anthracene/12-O
      tetradecanoylphorbol-13-acetate applications decreased the incidence of skin
      tumor in the Nrf2(+/+) mice when compared with the vehicle-treated group.
      Importantly, there was no chemoprotective effect elicited by sulforaphane
      pretreatment in the Nrf2(-/-) mice group. Taken together, our results show for
      the first time that Nrf2(-/-) mice are more susceptible to skin tumorigenesis and
      that the chemopreventive effects of sulforaphane are mediated, at least in part,
      through Nrf2.

PMID- 16912212
TI  - Prevalence and predictors of BRCA1 and BRCA2 mutations in a population-based
      study of breast cancer in white and black American women ages 35 to 64 years.
AB  - Although well studied in families at high-risk, the roles of mutations in the
      BRCA1 and BRCA2 genes are poorly understood in breast cancers in the general
      population, particularly in Black women and in age groups outside of the very
      young. We examined the prevalence and predictors of BRCA1 and BRCA2 mutations in
      1,628 women with breast cancer and 674 women without breast cancer who
      participated in a multicenter population-based case-control study of Black and
      White women, 35 to 64 years of age. Among cases, 2.4% and 2.3% carried
      deleterious mutations in BRCA1 and BRCA2, respectively. BRCA1 mutations were
      significantly more common in White (2.9%) versus Black (1.4%) cases and in Jewish
      (10.2%) versus non-Jewish (2.0%) cases; BRCA2 mutations were slightly more
      frequent in Black (2.6%) versus White (2.1%) cases. Numerous familial and
      demographic factors were significantly associated with BRCA1 and, to a lesser
      extent, BRCA2 carrier status, when examined individually. In models considering
      all predictors together, early onset ages in cases and in relatives, family
      history of ovarian cancer, and Jewish ancestry remained strongly and
      significantly predictive of BRCA1 carrier status, whereas BRCA2 predictors were
      fewer and more modest in magnitude. Both the combinations of predictors and
      effect sizes varied across racial/ethnic and age groups. These results provide
      first-time prevalence estimates for BRCA1/BRCA2 in breast cancer cases among
      understudied racial and age groups and show key predictors of mutation carrier
      status for both White and Black women and women of a wide age spectrum with
      breast cancer in the general population.

PMID- 16912213
TI  - Quantitative detection of p53 mutations in plasma DNA from tobacco smokers.
AB  - In lung tumors, the p53 tumor suppressor gene is commonly mutated with a
      characteristic mutation spectrum. The amount of and alterations in plasma DNA,
      such as mutations in p53, were associated with several cancers. Few studies used
      quantitative methods of high sensitivity. Previously, we observed p53 mutations
      in the noncancerous tissue that differed from those in lung tumors using the
      highly sensitive p53 mutation load assay. Based on our observation of an
      increased p53 mutation load in nontumorous lung tissue in smokers, we
      hypothesized that plasma DNA may contain mutant p53 indicative of tobacco smoke
      exposure and will be an effective biomarker of lung cancer or smoking exposure.
      We modified the p53 mutation load assay to detect mutations at p53 codons 248 and
      249, common mutations in lung cancer, in plasma DNA samples with a sensitivity of
      1:5,000. The assay was applied to a set of lung cancer cases (n = 39), hospital
      controls (n = 21), and population controls (n = 20) from a larger study. Controls
      were selected to consist of equal numbers of both ever and never smokers. The p53
      mutation load (mutated p53 copies per total number of p53 copies) was associated
      with smoking (P = 0.06), but not with lung cancer (P = 0.59). Most of the
      individuals with p53 mutations observed in plasma DNA were ever smokers and the
      p53 mutation load was higher in those who smoked for longer durations (P = 0.04).
      In summary, we were able to detect p53 mutations in plasma DNA from healthy
      individuals and our data suggest that p53 mutations in plasma DNA may be a marker
      of carcinogen exposure from tobacco smoke.

PMID- 16912214
TI  - Characterization of a catalytic ligand bridging metal ions in phosphodiesterases
      4 and 5 by molecular dynamics simulations and hybrid quantum mechanical/molecular
      mechanical calculations.
AB  - Cyclic nucleotide phosphodiesterases (PDEs) constitute a large superfamily of
      enzymes regulating concentrations of intracellular second messengers cAMP and
      cGMP through PDE-catalyzed hydrolysis. Although three-dimensional x-ray crystal
      structures of PDE4 and PDE5 have been reported, it is uncertain whether a
      critical, second bridging ligand (BL2) in the active site is H2O or HO- because
      hydrogen atoms cannot be determined by x-ray diffraction. The identity of BL2 is
      theoretically determined by performing molecular dynamics simulations and hybrid
      quantum mechanical/molecular mechanical (QM/MM) calculations, for the first time,
      on the protein structures resolved by x-ray diffraction. The computational
      results confirm our previous suggestion, which was based on QM calculations on a
      simplified active site model, that BL2 in PDE4 should be HO-, rather than H2O,
      serving as the nucleophile to initialize the catalytic hydrolysis of cAMP. The
      molecular dynamics simulations and QM/MM calculations on PDE5 demonstrate for the
      first time that the BL2 in PDE5 should also be HO- rather than H2O as proposed in
      recently published reports on the x-ray crystal structures, which serves as the
      nucleophile to initialize the PDE5-catalyzed hydrolysis of cGMP. These
      fundamental structural insights provide a rational basis for future structure
      based drug design targeting PDEs.

PMID- 16912215
TI  - Isostaticity and controlled force transmission in the cytoskeleton: A model
      awaiting experimental evidence.
AB  - A new model is proposed for force transmission through the cytoskeleton (CSK). A
      general discussion is first presented on the physical principles that underlie
      the modeling of this phenomenon. Some fundamental problems of conventional models
      -continuous and discrete--are examined. It is argued that mediation of focused
      forces is essential for good control over intracellular mechanical signals. The
      difficulties of conventional continuous models in describing such mediation are
      traced to a fundamental assumption rather than to their being continuous.
      Relevant advantages and disadvantages of continuous and discrete modeling are
      discussed. It is concluded that favoring discrete models is based on two
      misconceptions, which are clarified. The model proposed here is based on the idea
      that focused propagation of mechanical stimuli in frameworks over large distances
      (compared to the mesh size) can only occur when considerable regions of the CSK
      are isostatic. The concept of isostaticity is explained and a recently developed
      continuous isostaticity theory is briefly reviewed. The model enjoys several
      advantages: it leads to good control over force mediation; it explains nonuniform
      stresses and action at a distance; it is continuous, making it possible to model
      force propagation over long distances; and it enables prediction of individual
      force paths. To be isostatic, or nearly so, CSK networks must possess specific
      structural characteristics, and these are quantified. Finally, several
      experimental observations are interpreted using the new model and implications
      are discussed. It is also suggested that this approach may give insight into the
      dynamics of reorganization of the CSK. Many of the results are amenable to
      experimental measurements, providing a testing ground for the proposed picture,
      and generic experiments are suggested.

PMID- 16912216
TI  - Extraordinary rates of transition metal ion-mediated ribozyme catalysis.
AB  - In pre-steady-state, fast-quench kinetic analysis, the tertiary-stabilized
      hammerhead ribozyme "RzB" cleaves its substrate RNA with maximal measured k (obs)
      values of approximately 3000 min(-1) in 1 mM Mn(2+) and approximately 780 min(-1)
      in 1 mM Mg(2+) at 37 degrees C (pH 7.4). Apparent pKa for the catalytic general
      base is approximately 7.8-8.5, independent of the corresponding metal hydrate
      pKa, suggesting potential involvement of a nucleobase as general base as
      suggested previously from nucleobase substitution studies. The pH-rate profile is
      bell-shaped for Cd(2+), for which the general catalytic acid has a pKa of 7.3 +/-
      0.1. Simulations of the pH-rate relation suggest a pKa for the general catalytic
      acid to be approximately 9.5 in Mn(2+) and >9.5 in Mg(2+). The acid pKa's follow
      the trend in the pKa of the hydrated metal ions but are displaced by
      approximately 1-2 pH units in the presence of Cd(2+) and Mn(2+). One possible
      explanation for this trend is direct metal ion coordination with a nucleobase,
      which then acts as general acid.

PMID- 16912217
TI  - Sequence-specific RNA binding mediated by the RNase PH domain of components of
      the exosome.
AB  - We have previously demonstrated that PM-Scl-75, a component of the human exosome
      complex involved in RNA maturation and mRNA decay, can specifically interact with
      RNAs containing an AU-rich instability element. Through the analysis of a series
      of deletion mutants, we have now shown that a 266 amino acid fragment
      representing the RNase PH domain is responsible for the sequence-specific binding
      to AU-rich elements. Furthermore, we found that the RNase PH domains from two
      other exosomal components, OIP2 and RRP41, as well as from Escherichia coli
      polynucleotide phosphorylase, are all capable of specifically interacting with
      RNAs containing an AU-rich element with similar affinities. Finally, we
      demonstrate that the interaction of the RNase PH domain of PM-Scl-75 is readily
      competed by poly(U), but only inefficiently using other homopolymeric RNAs. These
      data demonstrate that RNase PH domains in general have an affinity for U- and AU
      rich sequences, and broaden the potential role in RNA biology of proteins
      containing these domains.

PMID- 16912218
TI  - Roles for the Trypanosoma brucei P2 transporter in DB75 uptake and resistance.
AB  - A novel trypanocide, 2,5-bis(4-amidinophenyl)furan (DB75), in its prodrug
      amidoxime-derivative form, 2,5-bis(4-amidinophenyl)furan-bis-O-methylamidoxime
      (DB289), is in trials as the first orally administered drug for human African
      trypanosomiasis. DB75 is a diamidine. Resistance to some diamidines correlates to
      loss of uptake via the P2 aminopurine transporter. We show here that uptake of
      DB75 into Trypanosoma brucei also occurs principally via the P2 transporter.
      Uptake of tritiated DB75 occurred via a high-affinity (K(m app), 3.2 microM)
      carriermediated route that was inhibited by adenosine, adenine, and pentamidine,
      all known substrates of the P2 transporter. Trypanosomes lacking the TbAT1 gene
      that encodes the P2 transporter demonstrated an 11-fold reduction in sensitivity
      to DB75 when measured under controlled in vitro conditions. These knockout cells
      were also less sensitive to DB75 than wild-type cells in mice. Initial uptake
      rates of DB75 into the Deltatbat1 knockout cell line were greatly reduced
      compared with rates in wild-type cells. A trypanosome cell line selected in vitro
      for DB75 resistance was shown to have lost P2-mediated DB75 uptake. The TbAT1
      gene was mapped to chromosome V of the T. brucei genome and the DB75-resistant
      parasites were shown to have deleted both alleles of this gene. Fluorescence
      microscopy of DB75-treated trypanosomes revealed that DB75 fluorescence localizes
      rapidly within the DNA-containing organelles of wild-type trypanosomes, whereas
      no fluorescence was observed in Deltatbat1-null parasites or in the parasites
      selected for resistance to DB75.

PMID- 16912219
TI  - A critical role for the short intracellular C terminus in receptor activity
      modifying protein function.
AB  - Receptor activity-modifying proteins (RAMPs) interact with and modify the
      behavior of the calcitonin receptor (CTR) and calcitonin receptor-like receptor
      (CLR). We have examined the contribution of the short intracellular C terminus,
      using constructs that delete the last eight amino acids of each RAMP. C-Terminal
      deletion of individual RAMPs had little effect on the signaling profile induced
      when complexed with CLR in COS-7 or human embryonic kidney (HEK)293 cells.
      Likewise, confocal microscopy revealed each of the mutant RAMPs translocated
      hemagglutinin-tagged CLR to the cell surface. In contrast, a pronounced effect of
      RAMP C-terminal truncation was seen for RAMP/CTRa complexes, studied in COS-7
      cells, with significant attenuation of amylin receptor phenotype induction that
      was stronger for RAMP1 and -2 than RAMP3. The loss of amylin binding upon C
      terminal deletion could be partially recovered with overexpression of Galpha(s),
      suggesting an impact of the RAMP C terminus on coupling of G proteins to the
      receptor complex. In HEK293 cells the c-Myc-RAMP1 C-terminal deletion mutant
      showed high receptor-independent cell surface expression; however, this construct
      showed low cell surface expression when expressed alone in COS-7 cells,
      indicating interaction of RAMPs with other cellular components via the C
      terminus. This mutant also had reduced cell surface expression when coexpressed
      with CTR. Thus, this study reveals important functionality of the RAMP C-terminal
      domain and identifies key differences in the role of the RAMP C terminus for CTR
      versus CLR-based receptors.

PMID- 16912220
TI  - Angiogenic cells can be rapidly mobilized and efficiently harvested from the
      blood following treatment with AMD3100.
AB  - Circulating endothelial progenitor cells (EPCs) are thought to contribute to
      angiogenesis following vascular injury, stimulating interest in their ability to
      mediate therapeutic angiogenesis. However, the number of EPCs in the blood is
      low, limiting endogenous repair, and a method to rapidly mobilize EPCs has not
      been reported. In this study, healthy donors were mobilized sequentially with the
      CXCR4 antagonist, AMD3100, and G-CSF. The number of EPCs and circulating
      angiogenic cells (CACs) in the blood and pheresis product was determined and the
      angiogenic capacity of each cell population assessed. Compared with baseline,
      treatment with AMD3100 or G-CSF increased the number of blood CACs 10.0-fold +/-
      4.4-fold and 8.8-fold +/- 3.7-fold, respectively. The number of EPCs in the blood
      increased 10.2-fold +/- 3.3-fold and 21.8-fold +/- 5.4-fold, respectively. On a
      percell basis, CACs harvested from G-CSF-mobilized blood displayed increased in
      vivo angiogenic potential compared with AMD3100-mobilized CACs. Mobilized EPCs
      displayed a greater proliferative capacity than EPCs isolated from baseline
      blood. Both CACs and EPCs were efficiently harvested by leukapheresis.
      Cryopreserved CACs but not EPCs retained functional activity after thawing. These
      data show that AMD3100 is a potent and rapid mobilizer of angiogenic cells and
      demonstrate the feasibility of obtaining and storing large numbers of angiogenic
      cells by leukapheresis.

PMID- 16912221
TI  - Syk-dependent mTOR activation in follicular lymphoma cells.
AB  - The mammalian target of rapamycin (mTOR) is emerging as a promising target for
      antitumor therapy. However, the mechanism that contributes to its regulation in B
      lymphomas remains unknown. This study shows that in follicular lymphoma (FL)
      cells, mTOR is active because the cells displayed rapamycin-sensitive
      phosphorylation of p70S6 kinase and 4E-BP1. Moreover, immunohistochemistry
      applied on lymph node tissue sections obtained from patients with FL revealed
      that, in most cases, p70S6 kinase was highly phosphorylated compared to normal
      tonsillar tissue. In FL cells, mTOR was under control of both phospholipase D
      (PLD) and phosphatidylinositol 3-kinase (PI3K). Moreover, we demonstrated that
      Syk plays a central role in mTOR activation because we found that both expression
      and activity are elevated compared to normal or chronic lymphocytic leukemia B
      cells. We also provide evidence that Syk operates through PLD- and PI3K
      independent pathways. Finally, Syk inhibition by piceatannol or by siRNA plasmids
      resulted in a potent inhibition of mTOR activity in FL cells, as well as in
      mantle cell lymphoma, Burkitt lymphoma, and diffuse large B-cell lymphoma. These
      findings suggest that the Syk-mTOR pathway has a critical function in FL
      survival, and therefore, that Syk could be a promising new target for B-lymphoma
      therapy.

PMID- 16912222
TI  - Characterization of stem cell-like cancer cells in immune-competent mice.
AB  - Recently, the cancer stem cell hypothesis has gained significant recognition as
      the descriptor of tumorigenesis. Although previous studies relied on
      transplanting human or rat tumor cells into immunecompromised mice, our study
      used the Hoechst 33342 dye-based side population (SP) technique to isolate and
      transplant stem cell-like cancer cells (SCLCCs) from the 4T1 and NXS2 murine
      carcinoma cell lines into the immune-competent microenvironment of syngeneic
      mice. 4T1 cells displayed an SP of 2% with a Sca-1(high)c-Kit(-)CD45(-)
      phenotype, whereas NXS2 cells contained an SP of 0.2% with a Sca
      1(high)CD24(high)c-Kit(-)CD45(-)GD (high)(2) phenotype. Reverse transcription
      polymerase chain reaction (RT-PCR) further revealed up-regulation in SP cells of
      ABCG2, Sca-1, Wnt-1, and TGF-beta2. Additionally, 4T1 and NXS2 SP cells exhibited
      increased resistance to chemotherapy, and 4T1 SP cells also showed an increased
      ability to efflux doxorubicin, which correlated with a selective increase in the
      percentage of SP cells found in the tumors of doxorubicin-treated mice. Most
      importantly, SP cells showed a markedly higher repopulation and tumorigenic
      potential in vivo, which correlated with an increased number of cells in the SP
      compartment of SP-derived tumors. Taken together, these results show that we
      successfully characterized SCLCCs from 2 murine carcinoma cell lines in the
      immune-competent microenvironment of syngeneic mice.

PMID- 16912223
TI  - High meningioma 1 (MN1) expression as a predictor for poor outcome in acute
      myeloid leukemia with normal cytogenetics.
AB  - The translocation t(12;22) involves MN1 and TEL and is rarely found in acute
      myeloid leukemia (AML). Recently, it has been shown in a mouse model that the
      fusion protein MN1-TEL can promote growth of primitive hematopoietic progenitor
      cells (HPCs) and, in cooperation with HOXA9, induce AML. We quantified MN1
      expression by real-time reverse transcriptase-polymerase chain reaction (RT-PCR)
      in 142 adult patients with AML with normal cytogenetics treated uniformly in
      trial AML-SHG 01/99. AML samples were dichotomized at the median MN1 expression.
      High MN1 expression was significantly correlated with unmutated NPM1 (P < .001),
      poor response to the first course of induction treatment (P = .02), a higher
      relapse rate (P = .03), and shorter relapse-free (P = .002) and overall survivals
      (P = .03). In multivariate analysis, MN1 expression was an independent prognostic
      marker (P = .02) in addition to age and Eastern Cooperative Oncology Group (ECOG)
      performance status. Excluding patients with NPM1(mutated)/FLT3ITD(negative), high
      MN1 expression was associated with shorter relapse-free survival (P = .057). MN1
      was highly expressed in some patients with acute lymphoblastic but not chronic
      lymphocytic or myeloid leukemia. MN1 was highly expressed in HPCs compared with
      differentiated cells and was down-regulated during in vitro differentiation of
      CD34(+) cells, suggesting a functional role in HPCs. In conclusion, our data
      suggest MN1 overexpression as a new prognostic marker in AML with normal
      cytogenetics.

PMID- 16912224
TI  - EXEL-0862, a novel tyrosine kinase inhibitor, induces apoptosis in vitro and ex
      vivo in human mast cells expressing the KIT D816V mutation.
AB  - Gain-of-function mutations of the receptor tyrosine kinase KIT play a key role in
      the pathogenesis of systemic mastocytosis (SM), gastrointestinal stromal tumors
      (GISTs), and some cases of acute myeloid leukemia (AML). Whereas KIT
      juxtamembrane domain mutations seen in most patients with GIST are highly
      sensitive to imatinib, the kinase activation loop mutant D816V, frequently
      encountered in SM, hampers the binding ability of imatinib. We investigated the
      inhibitory activity of the novel tyrosine kinase inhibitor EXEL-0862 against 2
      subclones of human mast cell line-1 (HMC-1)-HMC-1.1, harboring the juxtamembrane
      domain mutation V560G, and HMC-1.2, carrying V560G and the activation loop
      mutation D816V, found in more than 80% of patients with SM. EXEL-0862 inhibited
      the phosphorylation of KIT in a dose-dependent manner and decreased cell
      proliferation in both mast cell lines with higher activity against HMC-1.2 cells.
      The phosphorylation of KIT-dependent signal transducer and activator of
      transcription-3 (STAT3) and STAT5 was abrogated upon exposure to nanomolar
      concentrations of EXEL-0862. In addition, EXEL-0862 induced a time- and dose
      dependent proapoptotic effect in both mast cell lines and caused a significant
      reduction in mast-cell content in bone marrow samples from patients with SM
      harboring D816V and from those without the D816V mutation. We conclude that EXEL
      0862 is active against KIT activation loop mutants and is a promising candidate
      for the treatment of patients with SM and other KIT-driven malignancies harboring
      active site mutations.

PMID- 16912225
TI  - Histone deacetylase inhibitors increase virus gene expression but decrease CD8+
      cell antiviral function in HTLV-1 infection.
AB  - The dynamics of human T-lymphotropic virus type-1 (HTLV-1) provirus expression in
      vivo are unknown. There is much evidence to suggest that HTLV-1 gene expression
      is restricted: this restricted gene expression may contribute to HTLV-1
      persistence by limiting the ability of the HTLV-1-specific CD8(+) cell immune
      response to clear infected cells. In this study, we tested the hypothesis that
      derepression of HTLV-1 gene expression would allow an increase in CD8(+) cell
      mediated lysis of HTLV-1-infected cells. Using histone deacetylase enzyme
      inhibitors (HDIs) to hyperacetylate histones and increase HTLV-1 gene expression,
      we found that HDIs doubled Tax expression in naturally infected lymphocytes after
      overnight culture. However, the rate of CD8(+) cell-mediated lysis of Tax
      expressing cells ex vivo was halved. HDIs appeared to inhibit the CD8(+) cell
      mediated lytic process itself, indicating a role for the microtubule-associated
      HDAC6 enzyme. These observations indicate that HDIs may reduce the efficiency of
      cytotoxic T-cell (CTL) surveillance of HTLV-1 in vivo. The impact of HDIs on HTLV
      1 proviral load in vivo cannot be accurately predicted because of the widespread
      effects of these drugs on cellular processes; we therefore recommend caution in
      the use of HDIs in nonmalignant cases of HTLV-1 infection.

PMID- 16912226
TI  - A single high-affinity binding site for von Willebrand factor in collagen III,
      identified using synthetic triple-helical peptides.
AB  - The essential event in platelet adhesion to the injured blood vessel wall is the
      binding to subendothelial collagen of plasma von Willebrand factor (VWF), a
      protein that interacts transiently with platelet glycoprotein Ibalpha
      (GPIbalpha), slowing circulating platelets to facilitate firm adhesion through
      collagen receptors, including integrin alpha2beta1 and GpVI. To locate the site
      in collagen that binds VWF, we synthesized 57 overlapping triple-helical peptides
      comprising the whole triple-helical domain of collagen III. Peptide no. 23 alone
      bound VWF, with similar affinity to that of native collagen III. Immobilized
      peptide no. 23 supported platelet adhesion under static and flow conditions,
      processes blocked by an antibody that prevents collagen from binding the VWF A3
      domain. Truncated and alanine-substituted peptides derived from no. 23 either
      strongly interacted with both VWF and platelets or lacked both VWF and platelet
      binding. Thus, we identified the sequence RGQOGVMGF (O is hydroxyproline) as the
      minimal VWF-binding sequence in collagen III.

PMID- 16912227
TI  - Antigen recognition induces phosphatidylserine exposure on the cell surface of
      human CD8+ T cells.
AB  - In eukaryotic cells the phospholipid phosphatidylserine (PS) is restricted to the
      inner plasma-membrane leaflet. This lipid asymmetry, which is maintained by the
      concerted action of phospholipid transport proteins, is mainly lost during
      apoptosis. Here, we demonstrate that primary human CD8+ cytotoxic T lymphocytes
      (CTLs) expose PS on T-cell receptor (TCR)-mediated antigen (Ag) recognition. In
      contrast to PS externalization on apoptotic cells, activation-induced PS exposure
      is less pronounced and reversible. Fluorescence microscopic analysis revealed
      that PS is distributed nonhomogenously over the plasma membrane and concentrated
      in membrane lipid raft domains at the immunologic synapse. By studying the
      activity of PS transport proteins using a fluorescence-labeled PS analogue, we
      found that activation of CTLs inhibited the flippase-mediated inward-directed PS
      transport without affecting the outward transport. Shielding of exposed PS by
      annexin V protein during Ag recognition diminished cytokine secretion,
      activation, and cell-to-cell clustering of Ag-specific CTLs. In summary, our data
      demonstrate for the first time that externalized PS on Ag-stimulated CTLs is
      linked to T-cell activation and probably involved in cell-to-cell contact
      formation at the immunologic synapse.

PMID- 16912228
TI  - Clinical implications of FLT3 mutations in pediatric AML.
AB  - Activating mutations of the FLT3 gene occur because of an internal tandem
      duplication of the juxta-membrane domain (FLT3/ITD) or point mutation of the
      activation loop domain (FLT3/ALM). The presence of FLT3 mutations as well as the
      allelic ratio of FLT3/ITD (ITD-AR, mutant-wild type ratio) may have prognostic
      significance. FLT3 mutation status of 630 children with de novo acute myeloid
      leukemia (AML) treated on CCG-2941 and -2961 was determined, and ITD-AR was
      calculated for patients with FLT3/ITD. Clinical characteristics and outcomes for
      patients with FLT3/ALM and FLT3/ITD at varying ITD-ARs was determined and
      compared with those without FLT3 mutations (FLT3/WT). FLT3/ITD and FLT3/ALM were
      detected in 77 (12%) and 42 (6.7%) of the patients. Progression-free survival
      (PFS) was similar in patients with FLT3/ALM and FLT3/WT (51% versus 55%, P =
      .862). In contrast, PFS at 4 years from study entry for patients with FLT3/ITD
      was inferior to that of patients with FLT3/WT (31% versus 55%, P < .001). PFS
      decreased with increasing FLT3/ITD-AR (P < .001), and those with ITD-AR greater
      than 0.4 had a significantly worse PFS than those with lower ITD-AR (16% versus
      72%, P = .001) or with FLT3/WT (55%, P < .001). ITD-AR defines the prognostic
      significance in FLT3/ITD-positive AML, and ITD-AR greater than 0.4 is a
      significant and independent prognostic factor for relapse in pediatric AML.

PMID- 16912229
TI  - Molecular mimicry in the chronic myeloproliferative disorders: reciprocity
      between quantitative JAK2 V617F and Mpl expression.
AB  - An activating JAK2 mutation (JAK2 V617F) is present in the chronic
      myeloproliferative disorders (MPDs), polycythemia vera (PV), idiopathic
      myelofibrosis (IMF), and essential thrombocytosis (ET). JAK2 is also a chaperone
      for Mpl and responsible for its cell-surface expression. We observed a reciprocal
      relationship between neutrophil JAK2 V617F allele percentage and platelet Mpl
      expression in JAK2 V617F-positive PV, IMF, and ET patients. However, severely
      impaired platelet Mpl expression was present in JAK2 V617F-negative MPD patients.
      While JAK2 V617F allele status did not necessarily correlate with the clinical
      MPD phenotype, the degree of impaired platelet Mpl expression did. We conclude
      that multiple molecular abnormalities are involved in the pathogenesis of the
      MPDs and that aberrant Mpl expression may be a common denominator of aberrant
      signaling in both the JAK2 V617F-positive and JAK2 V617F-negative MPDs.

PMID- 16912231
TI  - SOCS up-regulation mobilizes autologous stem cells through CXCR4 blockade.
AB  - The chemokine CXCL12 influences self-renewal and differentiation of hematopoietic
      stem cell precursors in bone marrow by directing them toward specific stromalcell
      components. CXCL12 up-regulates members of the SOCS family through JAK/STAT
      activation, a mechanism that attenuates chemokine responses. SOCS expression may
      thus modulate retention of hematopoietic precursors (Sca-1(+) c-Kit(+)Lin(-)
      cells) in bone marrow. We show that in bovine growth hormone transgenic mice and
      in growth hormone-treated mice, SOCS up-regulation correlated with a large number
      of Sca-1(+) c-Kit(+)Lin(-) cells in blood. Retroviral transduction of SOCSs
      blocked in vitro migration of Sca-1(+)c-Kit(+)Lin(-) cells, as well as their
      capacity to reconstitute lethally irradiated mice. Furthermore, in lethally
      irradiated mice reconstituted with bone marrow infected by a tetracycline
      regulated, SOCS-expressing lentiviral vector, doxycycline treatment promoted
      rapid, extensive precursor mobilization to the periphery. The results indicate
      that by blocking CXCR4-mediated functions, SOCSs modulate hematopoietic precursor
      cell retention in bone marrow, and suggest the therapeutic interest of SOCS
      manipulation in several pathologic situations.

PMID- 16912230
TI  - Ikaros is required for plasmacytoid dendritic cell differentiation.
AB  - Plasmacytoid dendritic cells (pDCs) are specialized DCs that produce high levels
      of type I IFN upon viral infection. Despite their key immunoregulatory role,
      little is known about pDC ontogeny or how developmental events regulate their
      function. We show that mice expressing low levels of the transcription factor
      Ikaros (Ik(L/L)) lack peripheral pDCs, but not other DC subsets. Loss of pDCs is
      associated with an inability to produce type I IFN after challenge with Toll-like
      receptor-7 and -9 ligands, or murine cytomegalovirus (MCMV) infection. In
      contrast, conventional DCs are present in normal numbers and exhibit normal
      responses in vivo after challenge with MCMV or inactivated toxoplasma antigen.
      Interestingly, Ik(L/L) bone marrow (BM) cells contain a pDC population that
      appears blocked at the Ly-49Q- stage of differentiation and fails to terminally
      differentiate in response to Flt-3L, a cytokine required for pDC differentiation.
      This differentiation block is strictly dependent on a cell-intrinsic requirement
      for Ikaros in pDC-committed precursors. Global gene expression profiling of
      Ik(L/L) BM pDCs reveals an up-regulation of genes not normally expressed, or
      expressed at low levels, in WT pDCs. These studies suggest that Ikaros controls
      pDC differentiation by silencing a large array of genes.

PMID- 16912232
TI  - Human SLP-65 isoforms contribute differently to activation and apoptosis of B
      lymphocytes.
AB  - The SH2 domain-containing leukocyte adaptor protein of 65 kDa (SLP-65) is the key
      effector for signaling downstream of the B-cell antigen receptor (BCR). SLP-65
      controls not only B lymphopoiesis and humoral immunity but also possesses a yet
      poorly defined tumor suppressor activity that is lost in many cases of acute
      lymphoblastic leukemia. We found that the 2 isoforms of human SLP-65 are
      differentially involved in positive and negative B-cell signaling. Reconstitution
      experiments revealed that an atypical SH3 domain-binding motif, which is present
      in the long but not in the short SLP-65 isoform, mediates association to Grb2 and
      suppresses activation of mitogen-activated protein kinases p38 and JNK as well as
      up-regulation of c-Fos expression. In turn, the short isoform activates not only
      AP1-driven but also NF-kappaB-driven gene transcription more potently than the
      long isoform. Conversely, the long rather than the short SLP-65 isoform promotes
      BCR-induced B-cell apoptosis. Our data further delineate the structural
      requirements of positive and negative SLP-65 signal transduction in normal and
      neoplastic cells.

PMID- 16912233
TI  - Islet development: When glucagon's gone.

PMID- 16912234
TI  - Calcitonin--guardian of the Mammalian skeleton or is it just a fish story?

PMID- 16912235
TI  - FXR: More than a bile acid receptor?

PMID- 16912236
TI  - Role of monocarboxylate anion transporter 8 (MCT8) in thyroid hormone transport:
      Answers from mice.

PMID- 16912238
TI  - Prescribing and drug ingestion symbols and substances. 1976.

PMID- 16912239
TI  - Meddlesome medicine and rational therapeutics. 1975.

PMID- 16912241
TI  - Secondary hyperparathyroidism in chronic kidney disease: focus on clinical
      consequences and vitamin D therapies.
AB  - OBJECTIVE: To assess vitamin D-based treatment approaches for secondary
      hyperparathyroidism and its complications. DATA SOURCES: A literature search was
      performed using MEDLINE (1990-February 28, 2006). Key words used were chronic
      kidney disease and vitamin D to identify relevant papers published in English.
      STUDY SELECTION AND DATA EXTRACTION: From the database of articles generated, 48
      papers were identified. Titles and abstracts were examined to identify those
      directly related to the objective. Discussion was expanded through the
      bibliographies of cited articles. DATA SYNTHESIS: The increasing prevalence of
      chronic kidney disease (CKD) in the US indicates an urgent need for treatment
      strategies to delay or prevent disease progression. Abnormalities in phosphorus
      and calcium homeostasis, vitamin D levels, and the subsequent development of
      secondary hyperparathyroidism (SHPT) are secondary complications of CKD
      associated with increased morbidity and mortality. Management options include
      dietary phosphorus restriction, phosphate binders and/or calcium supplementation,
      vitamin D supplementation, and calcimimetics. Vitamin D supplementation has
      received increased attention given the prevalence of vitamin D deficiency in
      patients with CKD and the beneficial effect of correcting this deficiency.
      CONCLUSIONS: Early identification and intervention appropriate to the stage of
      CKD are likely to improve patient outcomes. Improved knowledge of interactions
      between vitamin D and vitamin D receptors has led to the development of vitamin D
      analogs and calcimimetics, which offer benefits in the management of SHPT.
      Integrating available treatment options into practice to achieve optimal
      therapeutic goals of SHPT based on the stage of CKD is a significant challenge
      for pharmacists managing patients with CKD.

PMID- 16912242
TI  - HHS-CDC news: the global HIV/AIDS pandemic, 2006.

PMID- 16912243
TI  - Escitalopram late in pregnancy and while breast-feeding.

PMID- 16912244
TI  - Can dantrolene contribute to methotrexate toxicity?

PMID- 16912245
TI  - Which pharmacists contribute to high-level pharmacotherapy audit meetings with
      general practitioners?
AB  - BACKGROUND: In the Netherlands, community pharmacists and general practitioners
      (GPs) collaborate in pharmacotherapy audit meetings (PTAMs) to optimize
      pharmacotherapy. OBJECTIVE: To identify associations between the quality level of
      PTAMs and characteristics of pharmacists. METHODS: We used a cross-sectional
      questionnaire design in a Dutch general practice and community pharmacy setting
      to estimate the contribution of pharmacists to the quality level of PTAMs. The
      questionnaire was sent to 123 community pharmacies working closely with 104 GP
      practices. The outcome variable was the quality level of PTAMs. The questionnaire
      provided information on 4 topics that were used as independent variables:
      characteristics of the PTAMs, provision of pharmacotherapy activities,
      characteristics of the pharmacists, and characteristics of the pharmacies.
      RESULTS: In total, 109 (88.6%) pharmacists completed the questionnaire, with 103
      participating in 62 different PTAMs. Seventeen pharmacists participated in level
      1 PTAMs (lowest level), 57 in level 2, 21 in level 3, and 8 in PTAMs at the
      highest level. The multinomial logistic regression identified only one
      significant association: pharmacists who participated in the highest quality
      level reported that they undertake initiatives in PTAMs (OR 2.98; 95% CI 1.07 to
      8.26) more frequently compared with pharmacists participating on the lowest
      level. CONCLUSIONS: In light of existing evidence, the role of pharmacists in
      PTAMs seems to be important. Pharmacists should create a distinct profile of
      their expertise, allowing them to professionalize PTAMs by undertaking more
      initiatives. PTAMs offer pharmacists a great opportunity to become integral
      members of the prescribing process.

PMID- 16912246
TI  - Physicians' perceived knowledge of and responsibility for managing patients' out
      of-pocket costs for prescription drugs.
AB  - BACKGROUND: Most insurers in the US have implemented incentive-based formularies
      that rely on out-of-pocket costs to influence prescription drug utilization.
      Medicare Part D plans have broadly adopted such benefit designs. OBJECTIVE: To
      evaluate physicians' perceptions of their knowledge of formularies and out-of
      pocket costs, factors that influence knowledge of costs, physicians' perceived
      responsibility for helping patients manage their out-of-pocket costs for
      prescription drugs, and physicians' perceptions of the role of pharmacists in
      managing these costs. METHODS: A multiple-choice survey was mailed to a random
      sample of 1200 physician members of the California Medical Association; a phone
      survey of nonresponders was then conducted. RESULTS: Of 1027 surveys delivered to
      correct addresses, 509 (49.6%) responses were received. Thirty-three percent of
      physicians reported that they were usually or always aware of patients'
      formularies and 20% were usually or always aware of patients' out-of-pocket costs
      for medications. Surgeons, emergency department physicians, and physicians that
      prescribe from more formularies than other physicians are less likely to be aware
      of patients' out-of-pocket costs, while physicians in large practices and those
      who use computers to prescribe are more aware. While 91% of physicians agreed
      that it is important that patients' out-of-pocket costs be managed, 40% somewhat
      or strongly agreed that it is their responsibility to help. Sixty-five percent of
      physicians believed that it is the responsibility of the pharmacist to be
      familiar with patients' out-of-pocket costs. CONCLUSIONS: Physicians often lack
      the knowledge to assist patients in the management of their out-of-pocket costs
      for prescription drugs and they depend on pharmacists to help patients manage
      those costs. Computer order entry and resources available in large physician
      organizations improve physicians' awareness of out-of-pocket costs when
      prescribing.

PMID- 16912247
TI  - Paradoxically decreased HDL-cholesterol levels associated with rosiglitazone
      therapy.
AB  - OBJECTIVE: To report 2 cases of very low high-density lipoprotein cholesterol
      (HDL-C) levels associated with rosiglitazone therapy. CASE SUMMARY: Two patients
      with type 2 diabetes taking rosiglitazone for glycemic control developed
      paradoxically low HDL-C levels during rosiglitazone therapy. In the first
      patient, the HDL-C level decreased from 33 to 11.6 mg/dL after 8 months of
      therapy. The second patient's HDL-C level decreased from the baseline level of
      44.8 mg/dL to 19.7 mg/dL after 4 months of rosiglitazone use. These abnormalities
      resolved on discontinuation of rosiglitazone and were not observed when the
      patients were treated with pioglitazone. The patients had no changes to other
      drug therapy or medical conditions known to affect lipid metabolism during
      treatment with rosiglitazone. DISCUSSION: Thiazolidinediones, insulin sensitizers
      widely used in the treatment of type 2 diabetes, have been reported to have
      beneficial effects on lipids, such as triglyceride lowering and HDL-C elevation,
      in addition to their glucose-lowering effects. It has been suggested that
      rosiglitazone and pioglitazone, the 2 currently available thiazolidinediones, may
      differ in their effects on lipids. As of July 2006, a total of 8 cases of
      paradoxical lowering of plasma HDL-C associated with rosiglitazone have now been
      reported. Based on use of the Naranjo probability scale, the 2 cases presented
      here were probably associated with rosiglitazone. The duration of therapy may be
      important in this paradoxical effect. CONCLUSIONS: Rosiglitazone is associated
      with a paradoxical decrease in HDL-C levels in patients with type 2 diabetes. In
      patients receiving rosiglitazone, a baseline lipid panel should be performed and
      lipid values should be monitored during the course of therapy.

PMID- 16912248
TI  - Poly-L-lactic acid for facial lipoatrophy in HIV.
AB  - OBJECTIVE: To review the clinical data for poly-L-lactic acid, a synthetic
      polymer used as an intradermal injection for the treatment of HIV associated
      facial fat loss (lipoatrophy). DATA SOURCES: A literature search was performed
      using MEDLINE (1966-August 2006). The search was limited to articles published in
      English and used the key words polylactic acid, polylactides, degradation,
      lipodystrophy, lipoatrophy, and HIV/AIDS. Dermik Laboratories was contacted to
      obtain unpublished information. Additional articles were retrieved from citations
      of selected references. STUDY SELECTION AND DATA EXTRACTION: Relevant information
      on the pharmacology, pharmacokinetics, safety, and efficacy of poly-L-lactic acid
      from clinical trials were selected. DATA SYNTHESIS: Poly-L-lactic acid (Sculptra)
      is a biocompatible, biodegradable, synthetic polymer able to be tailored into
      various desired morphologic features. It is approved by the Food and Drug
      Administration for the correction of facial lipoatrophy in people with HIV. Six
      clinical trials have evaluated the use of intradermal injections of poly-L-lactic
      acid. Results showed that cutaneous thickness is improved in patients receiving
      poly-L-lactic acid. Adverse effects included nodule and hematoma formation, as
      well as pain at the injection site. CONCLUSIONS: Poly-L-lactic acid offers a
      treatment alternative for patients with HIV-associated lipoatrophy. Further
      research is required in nonwhite populations.

PMID- 16912249
TI  - An update on evidence of clinical pharmacy services' impact on health-related
      quality of life.
AB  - OBJECTIVE: To describe and critique recent studies of clinical pharmacy services
      that have evaluated impact on health-related quality of life (HRQL) and to
      determine whether studies that lacked a control group were more likely to report
      a statistically significant impact on HRQL. DATA SOURCES: MEDLINE, EMBASE and
      International Pharmaceutical Abstracts were searched (March 1999-December 2004)
      using terms for HRQL and clinical pharmacy services. STUDY SELECTION AND DATA
      EXTRACTION: All original research articles in English identified from the data
      sources were examined. Abstracts were screened by 2 reviewers, and studies were
      included if a clinical pharmacy service was evaluated and pre-/post - HRQL
      outcomes were reported. DATA SYNTHESIS: Of 1152 citations identified by the
      literature search, 36 articles met the inclusion criteria. Twenty-two studies had
      a condition-specific focus. Fifteen studies incorporated a generic HRQL measure
      (primarily the short-form-36 items), 13 studies used a condition-specific
      measure, and 8 studies included both. Significant impact on one or more domains
      of HRQL was predominantly demonstrated in interventions relating to asthma,
      hypertension, and chronic heart failure. Statistically significant change in HRQL
      was reported in 8 of 21 studies that used a randomized controlled design (38%),
      in 2 of 5 studies with a nonrandomized design with control group (40%), and in 6
      of 8 studies without a control group (75%; chi2 2.00; p = 0.16). CONCLUSIONS:
      Since 1999, the number of published studies of clinical pharmacy services that
      evaluated HRQL as an endpoint has more than tripled. Study designs have improved
      in terms of longer length of follow-up, and a wider breadth of clinical services
      has been evaluated. Certain pharmacy services, such as asthma management, appear
      to offer the most convincing evidence for the value of clinical pharmacy services
      in terms of measurable short-term HRQL benefit.

PMID- 16912250
TI  - Choosing the appropriate antithrombotic agent for the prevention and treatment of
      VTE: a case-based approach.
AB  - OBJECTIVE: To review the risk of venous thromboembolism (VTE) in various patient
      populations and evaluate the agents available for the prevention and treatment of
      VTE using a case-based approach. DATA SOURCES: A MEDLINE search (1995-July 2006)
      was conducted to identify relevant literature. Additional references were
      reviewed from selected articles. STUDY SELECTION AND DATA EXTRACTION: Articles
      related to the prevention of VTE in orthopedic surgery, general surgery, and
      medically ill patients, as well as the treatment of VTE, were reviewed. DATA
      SYNTHESIS: Pharmacologic options for the prevention and treatment of VTE include
      warfarin, unfractionated heparin (UFH), low-molecular-weight heparins (LMWH), and
      fondaparinux. Current guidelines support the use of warfarin, LMWH, or
      fondaparinux for VTE prophylaxis following lower limb major orthopedic surgery.
      For VTE prophylaxis in hospitalized medical patients or patients undergoing
      general surgery, use of UFH and LMWH is supported; however, recent data on
      fondaparinux suggest that it is also effective in these patient populations. The
      use of UFH or LMWH (both in conjunction with warfarin) for treatment of acute
      deep venous thrombosis or nonmassive pulmonary embolism is recommended. Recent
      data suggest that fondaparinux (in conjunction with warfarin) is also effective
      for the treatment of VTE. A variety of pharmacokinetic, pharmacodynamic, and
      pharmacoeconomic factors differentiate each agent for the various indications.
      CONCLUSIONS: Currently, a "one-size-fits-all" anticoagulant is not available for
      treatment of VTE. A variety of patient factors, including type of surgery,
      medical indication, thrombotic risk factors, bleeding risk, history of heparin
      induced thrombocytopenia, and a variety of comorbid conditions can affect the
      safety, efficacy, and selection of appropriate VTE therapy.

PMID- 16912251
TI  - Increased adverse drug reactions to antimicrobials and anticonvulsants in
      patients with HIV infection.
AB  - OBJECTIVE: To review the incidence, signs, symptoms, and mechanisms of adverse
      drug reactions (ADRs) to sulfonamides, anticonvulsants, and antimycobacterial
      medications among people with HIV. DATA SOURCES: Searches of MEDLINE/PubMed (1980
      November 2005) and National Library of Medicine Meeting Abstracts (1989-November
      2005), as well as hand searches of journals and abstracts, were conducted to
      identify primary literature. Reference lists were reviewed to identify additional
      relevant reports. STUDY SELECTION AND DATA EXTRACTION: Relevant articles and
      abstracts, particularly of in vitro experiments and clinical studies, were
      compiled and reviewed. DATA SYNTHESIS: ADRs, especially in HIV-infected patients,
      are a cause for concern. Sulfonamides, anticonvulsants, and antimycobacterial
      drugs are commonly used to prevent and treat complications of HIV, including
      seizures and opportunistic infections. Patients with HIV have a much greater rate
      of ADRs to these drug classes, including severe and life-threatening
      hypersensitivity reactions. Several mechanisms of these ADRs have been
      postulated. Sulfamethoxazole and anticonvulsant hypersensitivity may involve the
      increased formation and decreased detoxification of reactive metabolites. The
      mechanisms for the marked increase in hypersensitivity ADRs to antimycobacterial
      drugs may be related to an altered immune profile in patients infected with both
      tuberculosis and HIV. CONCLUSIONS: ADRs to antimicrobial and anticonvulsant
      therapy cause markedly increased morbidity and mortality in HIV-positive
      patients. Further research involving the interaction between HIV and the
      increased ADRs to these drugs is required.

PMID- 16912252
TI  - Fulvestrant: pharmacologic profile versus existing endocrine agents for the
      treatment of breast cancer.
AB  - OBJECTIVE: To compare the pharmacologic profile of fulvestrant with that of
      tamoxifen and the aromatase inhibitors with respect to the choice of treatment
      for advanced breast cancer (ABC). DATA SOURCES: Principal literature and review
      articles were obtained from MEDLINE (1991-March 2006). Key search terms included
      fulvestrant, tamoxifen, aromatase inhibitors, pharmacology, and breast cancer.
      Further data sources were identified from the bibliographies of selected
      articles. STUDY SELECTION AND DATA EXTRACTION: English-language preclinical and
      clinical research and review articles reporting pharmacologic and safety data for
      fulvestrant, tamoxifen, and the aromatase inhibitors were evaluated to identify
      relevant information. Randomized clinical trial data were preferred over
      preclinical or Phase I and II trial data. DATA SYNTHESIS: A total of 52 clinical
      papers (including 10 reviews) and 17 clinical abstracts were evaluated reporting
      results from controlled Phase I-III studies and pilot studies. Eleven preclinical
      papers (including 2 reviews) and 6 preclinical abstracts were also included.
      Fulvestrant has little effect on sex hormone endocrinology, bone metabolism, and
      lipid biochemistry and appears unlikely to be the subject or cause of CYP3A4
      mediated drug interactions. Tamoxifen has a protective effect on bone (due to its
      partial estrogen agonist activity) and reduces plasma low-density lipoprotein
      cholesterol but increases triglyceride levels. The aromatase inhibitors have
      variable effects on lipid profiles and sex hormone endocrinology but have
      detrimental effects on bone due to inhibition of estrogen synthesis. Drug
      interactions have been noted between tamoxifen and anticoagulants and tamoxifen
      and aromatase inhibitors, which may be due to CYP-mediated mechanisms.
      CONCLUSIONS: Fulvestrant appears to have little effect on sex hormone
      endocrinology, bone metabolism, and lipid biochemistry and is unlikely to be
      subject to or the cause of CYP3A4-mediated drug-drug interactions. As such,
      fulvestrant represents a valuable new endocrine therapy for the treatment of ABC
      and broadens the options available to clinicians in the treatment of this
      disease.

PMID- 16912253
TI  - Comment: recent advances in neonatal pharmacotherapy.

PMID- 16912255
TI  - Fifth biannual report of the Cochrane Haematologic Malignancies Group--Focus on
      multiple myeloma.

PMID- 16912256
TI  - On the toxicity of chemotherapy for breast cancer--the need for vigilance.

PMID- 16912257
TI  - Respecting cancer drug transportability: a basis for successful lead selection.

PMID- 16912258
TI  - European move affects academic trials research.

PMID- 16912259
TI  - Two targets, one drug for new EGFR inhibitors.

PMID- 16912260
TI  - New finasteride trial results aim to curb controversy.

PMID- 16912261
TI  - Stat bite: Worldwide cancer control planning, 2006.

PMID- 16912262
TI  - Developing countries face growing cancer burden.

PMID- 16912263
TI  - Frequency and cost of chemotherapy-related serious adverse effects in a
      population sample of women with breast cancer.
AB  - BACKGROUND: The number, nature, and costs of serious adverse effects experienced
      by younger women receiving chemotherapy for breast cancer outside of clinical
      trials are unknown. METHODS: From a database of medical claims made by
      individuals with employer-provided health insurance between January 1998 and
      December 2002, we identified 12,239 women 63 years of age or younger with newly
      diagnosed breast cancer, of whom 4075 received chemotherapy during the 12 months
      after the initial breast cancer diagnosis and 8164 did not. Diagnostic codes for
      eight chemotherapy-related adverse effects were identified. Total
      hospitalizations for all causes, hospitalizations or emergency room visits for
      adverse effects that are typically related to chemotherapy, and health care
      expenditures were compared between the two groups of women. All statistical tests
      were two-sided. RESULTS: Women who received chemotherapy were more likely than
      those who did not to be hospitalized or to visit the emergency room for all
      causes (61% versus 42%; mean difference = 19%, 95% confidence interval [CI] =
      16.7% to 21.3%, P<.001) and for chemotherapy-related serious adverse effects (16%
      versus 5%, mean difference = 11%, 95% CI = 9.6% to 12.4%, P<.001). The
      percentages of chemotherapy recipients who were hospitalized or visited the
      emergency room during the year after their breast cancer diagnosis were 8.4% for
      fever or infection; 5.5% for neutropenia or thrombocytopenia; 2.5% for
      dehydration or electrolyte disorders; 2.4% for nausea, emesis, or diarrhea; 2.2%
      for anemia; 2% for constitutional symptoms; 1.2% for deep venous thrombosis or
      pulmonary embolus; and 0.9% for malnutrition. Chemotherapy recipients incurred
      large incremental expenditures for chemotherapy-related serious adverse effects
      (1271 dollars per person per year) and ambulatory encounters (17,617 dollars per
      person per year). CONCLUSIONS: Chemotherapy-related serious adverse effects among
      younger, commercially insured women with breast cancer may be more common than
      reported by large clinical trials and lead to more patient suffering and health
      care expenditures than previously estimated.

PMID- 16912264
TI  - Use of three-dimensional tissue cultures to model extravascular transport and
      predict in vivo activity of hypoxia-targeted anticancer drugs.
AB  - BACKGROUND: Because of the inefficient vasculature of solid tumors, anticancer
      drugs must penetrate relatively long distances through the extravascular
      compartment. The requirement for such diffusion may limit their activity,
      especially that of hypoxia-targeted drugs. We tested whether a three-dimensional
      pharmacokinetic/pharmacodynamic (PK/PD) model based on a representative mapped
      tumor microvascular network could predict the therapeutic activity of anticancer
      drugs in mouse xenograft tumors. METHODS: Diffusion coefficients of the hypoxia
      activated anticancer drug tirapazamine (TPZ) and of 15 TPZ analogs were estimated
      by measuring their transport through HT29 colon cancer multicellular layers
      (MCLs). Anoxic cytotoxic potency (by clonogenic assay) and metabolism of the TPZ
      analogs were measured in HT29 cell suspensions, and their plasma pharmacokinetics
      was measured in CD-1 nude mice. This information was used to create a spatially
      resolved PK/PD model for the tumor microvascular network. Model predictions were
      compared with actual hypoxic cell kill as measured by clonogenic assays on HT29
      xenograft tumors 18 hours after treatment with each TPZ analog. RESULTS: Modeling
      TPZ transport in the tumor microvascular network showed substantial drug
      depletion in the most hypoxic regions, with predicted maximum cell kill of only 3
      logs, compared with more than 10 logs if there were no transport impediment. A
      large range of tissue diffusion coefficients (0.027 x 10(-6)-1.87 x 10(-6) cm2/s)
      was observed for the TPZ analogs. There was a strong correlation between model
      predicted and measured hypoxic cell kill (R2 = 0.89) but a poor correlation when
      the model did not include extravascular transport (R2 = 0.32). CONCLUSIONS:
      Extravascular transport in tumors, and its consequences for tumor cell killing,
      can be predicted by measuring drug penetration through MCLs in vitro and modeling
      pharmacokinetics at each position in three-dimensional microvascular networks.

PMID- 16912265
TI  - Effect of finasteride on the sensitivity of PSA for detecting prostate cancer.
AB  - BACKGROUND: In the Prostate Cancer Prevention Trial (PCPT), men receiving
      finasteride had a 24.8% lower risk of prostate cancer than men receiving placebo
      but a higher risk of high-grade cancer. We examined the impact of finasteride on
      the sensitivity and area under the receiver operating characteristic curve (AUC)
      of prostate-specific antigen (PSA) for detecting prostate cancer. METHODS: We
      studied men in the placebo and finasteride groups of the PCPT who had a prostate
      biopsy and concurrent PSA tests during the 7-year study. We compared the placebo
      and finasteride groups for sensitivity and AUC of PSA for the detection of all
      prostate cancer, of Gleason grade 7 or higher prostate cancer, and of Gleason
      grade 8 or higher prostate cancer. All statistical tests were two-sided. RESULTS:
      Of 5112 men in the placebo group, prostate cancer was detected in 1111. Gleason
      tumor grade was available for 1100 men, of whom 240 had grade 7 or higher and 55
      had grade 8 or higher. Of 4579 men in the finasteride group, 695 had prostate
      cancer. Gleason grade was available for 686 men, of whom 264 had grade 7 or
      higher and 81 had grade 8 or higher. The AUC of PSA for all outcomes was greater
      for the finasteride group than the placebo group. For detecting prostate cancer
      versus no cancer, the AUCs were 0.757 and 0.681, respectively (P < .001); for
      detecting Gleason grade > or = 7 versus < or = 6 or no cancer, the AUCs were
      0.838 and 0.781, respectively (P = .003); and for detecting Gleason grade > or =
      8 versus < or = 7 or no cancer, the AUCs were 0.886 and 0.824, respectively (P =
      .071). The sensitivity of PSA was higher for men in the finasteride group than in
      the placebo group at all PSA cutoffs matched by specificity. CONCLUSIONS: PSA had
      statistically significantly better sensitivity and AUC for detecting prostate
      cancer in the finasteride arm of the PCPT than in the placebo arm. This bias
      would be expected to contribute to greater detection of all grades of prostate
      cancer with finasteride.

PMID- 16912266
TI  - Incidence of initial local therapy among men with lower-risk prostate cancer in
      the United States.
AB  - BACKGROUND: The frequently indolent nature of early-stage prostate cancer in
      older men and in men with low- or moderate-grade tumors and the demonstration
      that the survival benefits of radical prostatectomy are primarily among men
      younger than 65 years have led to concerns about prostate cancer overtreatment.
      METHODS: Using data from 13 Surveillance, Epidemiology, and End Results
      registries, we performed a retrospective cohort study of 71,602 men who were
      diagnosed with localized or regional prostate cancer between 2000 and 2002. We
      quantified the incidence of initial curative therapy (i.e., surgery or radiation
      therapy) among men with lower-risk cancers as defined by their limited likelihood
      of either dying from expectantly managed prostate cancer or achieving a survival
      benefit from local therapy. Stratified analyses and multinomial logistic
      regression models were used to quantify the absolute and relative rates of
      curative therapy among men in various age-grade strata. All statistical tests
      were two-sided. RESULTS: We identified 24,405 men with lower-risk prostate
      cancers and complete data for the first course of treatment. Initial curative
      therapy was undertaken in 13,537 of these men (55%); 81% of treated men received
      radiation therapy. The likelihood of curative therapy, relative to expectant
      management, varied statistically significantly among lower-risk age-grade strata
      (all P<.05). Assuming that initial expectant management is appropriate for all
      lower-risk cancers, 2564 men (10%) in this population-based sample were
      overtreated with radical prostatectomy and 10,973 (45%) with radiation therapy.
      CONCLUSIONS: These data quantify a target population for whom greater use of
      expectant approaches may reduce overtreatment and improve the quality of
      localized prostate cancer care.

PMID- 16912267
TI  - Effect of bortezomib on human neuroblastoma cell growth, apoptosis, and
      angiogenesis.
AB  - BACKGROUND: Bortezomib is a selective and reversible inhibitor of the 26S
      proteasome that shows potent antitumor activity in vitro and in vivo against
      several human cancers of adulthood. No data are available on bortezomib activity
      against human pediatric neuroblastoma. METHODS: Ten neuroblastoma cell lines and
      suspensions of primary neuroblastoma cells from three patients were tested for
      sensitivity to bortezomib. Colony formation, cell proliferation, cell cycle
      progression, and apoptosis were evaluated by a clonogenic assay and by measuring
      3H-thymidine incorporation, bromodeoxyuridine uptake, DNA fragmentation, and
      phosphatidylserine exposure and propidium iodide staining, respectively.
      Angiogenesis was assessed by the chick embryo chorioallantoic membrane (CAM)
      assay. Two mouse xenograft models that mimic the growth and spread of
      neuroblastoma in humans were used to examine in vivo sensitivity of neuroblastoma
      to bortezomib. All statistical tests were two-sided. RESULTS: Bortezomib
      inhibited proliferation and colony formation of neuroblastoma cell lines in a
      time- and dose-dependent manner. The mean bortezomib concentration that caused
      50% inhibition of growth was 6.1 nM (95% confidence interval [CI] = 0.9 to 11.3
      nM) at 72 hours. Bortezomib-treated neuroblastoma cells were arrested at G2/M and
      underwent apoptosis (mean percentage of apoptotic cells in four neuroblastoma
      cell lines treated with 20 nM bortezomib for 24 hours ranged from 20% to 35%, and
      caspases were activated by two- to fivefold with respect to untreated cells).
      Similar results were obtained for primary neuroblastoma cells exposed to
      bortezomib. Bortezomib inhibited angiogenesis in CAMs stimulated by conditioned
      medium from neuroblastoma cell lines, by neuroblastoma xenografts, and by primary
      neuroblastoma biopsy specimens (microvessel area: 2.9 x 10(-2) mm2, 95% CI = 1.8
      x 10(-2) to 3.8 x 10(-2) mm2 in CAMs treated with biopsy specimens alone and 1.3
      x 10(-2) mm2, 95% CI = 1 x 10(-2) to 1.5 x 10(-2) mm2 in CAMs treated with biopsy
      specimens plus bortezomib, P = .024). In both mouse models, mice treated with
      bortezomib lived statistically significantly longer than control mice (mean
      survival time in the pseudometastatic model: 74.2 versus 50.3 days, P<.001; mean
      survival time in the orthotopic model: 72.3 versus 50.6 days, P<.001).
      CONCLUSIONS: Bortezomib is an effective inhibitor of neuroblastoma cell growth
      and angiogenesis. These findings provide the rationale for further clinical
      investigation of bortezomib in pediatric neuroblastoma.

PMID- 16912268
TI  - Carbonated soft drinks and risk of esophageal adenocarcinoma: a population-based
      case-control study.
AB  - The increased intake of carbonated soft drinks parallels the incidence of
      esophageal adenocarcinoma. To determine whether an association exists between
      carbonated drink intake and esophageal and cardia adenocarcinoma, we analyzed
      data from a Swedish nationwide, population-based, case-control study. During data
      collection in 1995-1997, 189 patients with esophageal adenocarcinoma (88% of all
      eligible), 262 patients with cardia adenocarcinoma (84%), and 820 control
      subjects (73%) were interviewed in person. All cancers were histologically
      classified. We calculated odds ratios with 95% confidence intervals using
      conditional logistic regression and multivariable analyses. Frequency of intake
      of carbonated soft drinks was not associated with risk of esophageal
      adenocarcinoma; high consumers (intake more than six times weekly) were at a
      statistically nonsignificantly decreased risk compared with never users (odds
      ratio = 0.89, 95% confidence interval = 0.49 to 1.64). Consumption of carbonated
      low-alcohol beer and combined intake of carbonated drinks were not associated
      with risk of esophageal adenocarcinoma. No association between intake of
      carbonated soft drinks or low-alcohol beer and risk of cardia adenocarcinoma was
      observed.

PMID- 16912269
TI  - Re: Randomized trial of letrozole following tamoxifen as extended adjuvant
      therapy in receptor-positive breast cancer: updated findings from NCIC CTG MA.17.

PMID- 16912270
TI  - Malignant melanoma: genetics and therapeutics in the genomic era.
AB  - Cell for cell, probably no human cancer is as aggressive as melanoma. It is among
      a handful of cancers whose dimensions are reported in millimeters. Tumor
      thickness approaching 4 mm presents a high risk of metastasis, and a diagnosis of
      metastatic melanoma carries with it an abysmal median survival of 6-9 mo. What
      features of this malignancy account for such aggressive behavior? Is it the
      migratory history of its cell of origin or the programmed adaptation of its
      differentiated progeny to environmental stress, particularly ultraviolet
      radiation? While the answers to these questions are far from complete, major
      strides have been made in our understanding of the cellular, molecular, and
      genetic underpinnings of melanoma. More importantly, these discoveries carry
      profound implications for the development of therapies focused directly at the
      molecular engines driving melanoma, suggesting that we may have reached the brink
      of an unprecedented opportunity to translate basic science into clinical
      advances. In this review, we attempt to summarize our current understanding of
      the genetics and biology of this disease, drawing from expanding genomic
      information and lessons from development and genetically engineered mouse models.
      In addition, we look forward toward how these new insights will impact on
      therapeutic options for metastatic melanoma in the near future.

PMID- 16912271
TI  - Polyglutamine neurodegenerative diseases and regulation of transcription:
      assembling the puzzle.
AB  - The polyglutamine disorders are a class of nine neuro-degenerative disorders that
      are inherited gain-of-function diseases caused by expansion of a translated CAG
      repeat. Even though the disease-causing proteins are widely expressed, specific
      collections of neurons are more susceptible in each disease, resulting in
      characteristic patterns of pathology and clinical symptoms. One hypothesis poses
      that altered protein function is fundamental to pathogenesis, with protein
      context of the expanded polyglutamine having key roles in disease-specific
      processes. This review will focus on the role of the disease-causing
      polyglutamine proteins in gene transcription and the extent to which the mutant
      proteins induce disruption of transcription.

PMID- 16912272
TI  - Keystone meeting summary: 'Adipogenesis, obesity, and inflammation' and 'Diabetes
      mellitus and the control of cellular energy metabolism, ' January 21-26, 2006,
      Vancouver, Canada.
AB  - The dysregulation of specific cellular functions in adipocytes, muscle cells,
      beta cells, and the liver leads to changes in systemic metabolic processes and
      ultimately to the pathophysiological manifestations that cause type 2 diabetes.
      The underlying cellular mechanisms are complex. The two meetings summarized here
      aimed to highlight the recent advances in our understanding of the molecular
      basis of feeding and nutrient storage and on the molecular consequences of
      obesity in terms of promoting risk for type 2 diabetes and cardiovascular
      disease.

PMID- 16912273
TI  - Spleen versus pancreas: strict control of organ interrelationship revealed by
      analyses of Bapx1-/- mice.
AB  - During early stages of pancreatic development, the mesenchyme that contributes to
      the spleen overlies the dorsal pancreatic endoderm. Here, we show that
      interactions between splenic mesenchyme and pancreas proceed via a highly
      orchestrated morphogenetic program. Disruption of morphogenesis, as occurs in the
      Bapx1(Nkx3.2)(-/-) embryo, results in transformation of these tissues into well
      organized, ectopic gut-like structures. Bapx1 plays a crucial organizing role
      effecting position and separation of the spleen and pancreas to prevent this
      metaplastic transformation. Similar transformations occur in organ cultures
      employing wild-type pancreatic endoderm and spleen mesenchyme, revealing the
      developmental plasticity of the pancreas and that precise spatial and temporal
      control of tissue interactions are required for development of both organs.

PMID- 16912274
TI  - A novel role for Xist RNA in the formation of a repressive nuclear compartment
      into which genes are recruited when silenced.
AB  - During early mammalian female development, one of the two X chromosomes becomes
      inactivated. Although X-chromosome coating by Xist RNA is essential for the
      initiation of X inactivation, little is known about how this signal is
      transformed into transcriptional silencing. Here we show that exclusion of RNA
      Polymerase II and transcription factors from the Xist RNA-coated X chromosome
      represents the earliest event following Xist RNA accumulation described so far in
      differentiating embryonic stem (ES) cells. Paradoxically, exclusion of the
      transcription machinery occurs before gene silencing is complete. However,
      examination of the three-dimensional organization of X-linked genes reveals that,
      when transcribed, they are always located at the periphery of, or outside, the
      Xist RNA domain, in contact with the transcription machinery. Upon silencing,
      genes shift to a more internal location, within the Xist RNA compartment devoid
      of transcription factors. Surprisingly, the appearance of this compartment is not
      dependent on the A-repeats of the Xist transcript, which are essential for gene
      silencing. However, the A-repeats are required for the relocation of genes into
      the Xist RNA silent domain. We propose that Xist RNA has multiple functions: A
      repeat-independent creation of a transcriptionally silent nuclear compartment;
      and A-repeat-dependent induction of gene repression, which is associated with
      their translocation into this silent domain.

PMID- 16912275
TI  - Full and partial genome-wide assembly and disassembly of the yeast transcription
      machinery in response to heat shock.
AB  - Eukaryotic genes are controlled by sequence-specific DNA-binding proteins,
      chromatin regulators, general transcription factors, and elongation factors. Here
      we examine the genome-wide location of representative members of these groups and
      their redistribution when the Saccharomyces cerevisiae genome is reprogrammed by
      heat shock. As expected, assembly of active transcription complexes is coupled to
      eviction of H2A.Z nucleosomes, and disassembly is coupled to the return of
      nucleosomes. Remarkably, a large number of promoters assemble into partial
      preinitiation complexes (partial PICs), containing TFIIA, TFIID (and/or SAGA),
      TFIIB, TFIIE, and TFIIF. However, RNA polymerase II and TFIIH are generally not
      recruited, and nucleosomes are not displaced. These promoters may be preparing
      for additional stress that naturally accompany heat stress. For example, we find
      that oxidative stress, which often occurs with prolonged exposure of cells to
      high temperature, converts partial PICs into full PICs. Partial PICs therefore
      represent novel regulated intermediates that assemble at promoters in the midst
      of chromatin.

PMID- 16912276
TI  - The Forkhead transcription factor Hcm1 regulates chromosome segregation genes and
      fills the S-phase gap in the transcriptional circuitry of the cell cycle.
AB  - Transcription patterns shift dramatically as cells transit from one phase of the
      cell cycle to another. To better define this transcriptional circuitry, we
      collected new microarray data across the cell cycle of budding yeast. The
      combined analysis of these data with three other cell cycle data sets identifies
      hundreds of new highly periodic transcripts and provides a weighted average peak
      time for each transcript. Using these data and phylogenetic comparisons of
      promoter sequences, we have identified a late S-phase-specific promoter element.
      This element is the binding site for the forkhead protein Hcm1, which is required
      for its cell cycle-specific activity. Among the cell cycle-regulated genes that
      contain conserved Hcm1-binding sites, there is a significant enrichment of genes
      involved in chromosome segregation, spindle dynamics, and budding. This may
      explain why Hcm1 mutants show 10-fold elevated rates of chromosome loss and
      require the spindle checkpoint for viability. Hcm1 also induces the M-phase
      specific transcription factors FKH1, FKH2, and NDD1, and two cell cycle-specific
      transcriptional repressors, WHI5 and YHP1. As such, Hcm1 fills a significant gap
      in our understanding of the transcriptional circuitry that underlies the cell
      cycle.

PMID- 16912278
TI  - Plasticity and expanding complexity of the hepatic transcription factor network
      during liver development.
AB  - Cross-regulatory cascades between hepatic transcription factors have been
      implicated in the determination of the hepatic phenotype. Analysis of
      recruitments to regulatory regions and the temporal and spatial expression
      pattern of the main hepatic regulators during liver development revealed a
      gradual increase in complexity of autoregulatory and cross-regulatory circuits.
      Within these circuits we identified a core group of six transcription factors,
      which regulate the expression of each other and the expression of other
      downstream hepatic regulators. Changes in the promoter occupancy patterns during
      development included new recruitments, release, and exchange of specific factors.
      We also identified promoter and developmental stage-specific dual regulatory
      functions of certain factors as an important feature of the network. Inactivation
      of HNF-4alpha in embryonic, but not in adult, liver resulted in the diminished
      expression of most hepatic factors, demonstrating that the stability of the
      network correlates with its complexity. The results illustrate the remarkable
      flexibility of a self-sustaining transcription factor network, built up by
      complex dominant and redundant regulatory motifs in developing hepatocytes.

PMID- 16912277
TI  - C. elegans GLA-3 is a novel component of the MAP kinase MPK-1 signaling pathway
      required for germ cell survival.
AB  - During oocyte development in Caenorhabditis elegans, approximately half of all
      developing germ cells undergo apoptosis. While this process is evolutionarily
      conserved from worms to humans, the regulators of germ cell death are still
      largely unknown. In a genetic screen for novel genes involved in germline
      apoptosis in Caenorhabditis elegans, we identified and cloned gla-3. Loss of gla
      3 function results in increased germline apoptosis and reduced brood size due to
      defective pachytene exit from meiosis I. gla-3 encodes a TIS11-like zinc-finger
      containing protein that is expressed in the germline, from the L4 larval stage to
      adulthood. Biochemical evidence and genetic epistasis analysis revealed that GLA
      3 participates in the MAPK signaling cascade and directly interacts with the C.
      elegans MAPK MPK-1, an essential meiotic regulator. Our results show that GLA-3
      is a new component of the MAPK cascade that controls meiotic progression and
      apoptosis in the C. elegans germline and functions as a negative regulator of the
      MAPK signaling pathway during vulval development and in muscle cells.

PMID- 16912279
TI  - c-Jun/AP-1 controls liver regeneration by repressing p53/p21 and p38 MAPK
      activity.
AB  - The AP-1 transcription factor c-Jun is a key regulator of hepatocyte
      proliferation. Mice lacking c-Jun in the liver (c-jun (Deltali*)) display
      impaired liver regeneration after partial hepatectomy (PH). This phenotype
      correlates with increased protein levels of the cdk-inhibitor p21 in the liver.
      We performed PH experiments in several double-knockout mouse models to
      genetically identify the signaling events regulated by c-Jun. Inactivation of p53
      in c-jun (Deltali*) mice abrogated both hepatocyte cell cycle block and increased
      p21 protein expression. Consistently, liver regeneration was rescued in c-jun
      (Deltali*) p21 (-/-) double-mutant mice. This indicated that c-Jun controls
      hepatocyte proliferation by a p53/p21-dependent mechanism. Analyses of p21 mRNA
      and protein expression in livers of c-jun (Deltali*) mice after PH revealed that
      the accumulation of p21 protein is due to a post-transcriptional/post
      translational mechanism. We have investigated several candidate pathways
      implicated in the regulation of p21 expression, and observed increased activity
      of the stress kinase p38 in regenerating livers of c-jun (Deltali*) mice.
      Importantly, conditional deletion of p38alpha in livers of c-jun (Deltali*) mice
      fully restored hepatocyte proliferation and attenuated increased p21 protein
      levels after PH. These data demonstrate that c-Jun/AP-1 regulates liver
      regeneration through a novel molecular pathway that involves p53, p21, and the
      stress kinase p38alpha.

PMID- 16912280
TI  - The flagellar-specific transcription factor, sigma28, is the Type III secretion
      chaperone for the flagellar-specific anti-sigma28 factor FlgM.
AB  - The sigma(28) protein is a member of the bacterial sigma(70)-family of
      transcription factors that directs RNA polymerase to flagellar late (class 3)
      promoters. The sigma(28) protein is regulated in response to flagellar assembly
      by the anti-sigma(28) factor FlgM. FlgM inhibits sigma(28)-dependent
      transcription of genes whose products are needed late in assembly until the
      flagellar basal motor structure, the hook-basal body (HBB), is constructed. A
      second function for the sigma(28) transcription factor has been discovered:
      sigma(28) facilitates the secretion of FlgM through the HBB, acting as the FlgM
      Type III secretion chaperone. Transcription-specific mutants in sigma(28) were
      isolated that remained competent for FlgM-facilitated secretion separating the
      transcription and secretion-facilitation activities of sigma (28). Conversely, we
      also describe the isolation of mutants in sigma(28) that are specific for FlgM
      facilitated secretion. The data demonstrate that sigma(28) is the Type III
      secretion chaperone for its own anti-sigma factor FlgM. Thus, a novel role for a
      sigma(70)-family transcription factor is described.

PMID- 16912281
TI  - Human T-cell leukemia virus type 1 (HTLV-1) and HTLV-2 use different receptor
      complexes to enter T cells.
AB  - Studies using adherent cell lines have shown that glucose transporter-1 (GLUT-1)
      can function as a receptor for human T-cell leukemia virus type 1 (HTLV). In
      primary CD4(+) T cells, heparan sulfate proteoglycans (HSPGs) are required for
      efficient entry of HTLV-1. Here, the roles of HSPGs and GLUT-1 in HTLV-1 and HTLV
      2 Env-mediated binding and entry into primary T cells were studied. Examination
      of the cell surface of activated primary T cells revealed that CD4(+) T cells,
      the primary target of HTLV-1, expressed significantly higher levels of HSPGs than
      CD8(+) T cells. Conversely, CD8(+) T cells, the primary target of HTLV-2,
      expressed GLUT-1 at dramatically higher levels than CD4(+) T cells. Under these
      conditions, the HTLV-2 surface glycoprotein (SU) binding and viral entry were
      markedly higher on CD8(+) T cells while HTLV-1 SU binding and viral entry were
      higher on CD4(+) T cells. Binding studies with HTLV-1/HTLV-2 SU recombinants
      showed that preferential binding to CD4(+) T cells expressing high levels of
      HSPGs mapped to the C-terminal portion of SU. Transfection studies revealed that
      overexpression of GLUT-1 in CD4(+) T cells increased HTLV-2 entry, while
      expression of HSPGs on CD8(+) T cells increased entry of HTLV-1. These studies
      demonstrate that HTLV-1 and HTLV-2 differ in their T-cell entry requirements and
      suggest that the differences in the in vitro cellular tropism for transformation
      and in vivo pathobiology of these viruses reflect different interactions between
      their Env proteins and molecules on CD4(+) and CD8(+) T cells involved in entry.

PMID- 16912282
TI  - Gammaherpesvirus persistence alters key CD8 T-cell memory characteristics and
      enhances antiviral protection.
AB  - In herpesvirus infections, the virus persists for life but is contained through T
      cell-mediated immune surveillance. How this immune surveillance operates is
      poorly understood. Recent studies of other persistent infections have indicated
      that virus persistence is associated with functional deficits in the CD8(+) T
      cell response. To test whether this is the case in a herpesvirus infection, we
      used a mutant murine gammaherpesvirus that is defective in its ability to persist
      in the host. By comparing the immune response to this virus with a revertant
      virus that can persist, we were able to dissect the changes in the antiviral
      CD8(+) T-cell response that are induced by virus persistence. Surprisingly,
      persistently infected mice controlled a secondary challenge infection more
      rapidly than nonpersistently infected mice, indicating enhanced rather than
      diminished effector functions. Consistent with this, virus-specific CD8 T cells
      from these mice exhibited faster upregulation of the cytotoxic mediator granzyme
      B. Another unexpected finding was that CD8(+) T cells from neither infection
      responded efficiently to homeostatic cytokines. The unresponsiveness of the
      memory cells from the nonpersistently infected mice appears to be linked to the
      prolonged replication of virus within the lungs. Other changes seen in different
      chronic infection models were also observed, such as changes in Bcl-2 levels,
      interleukin-2 production, and the immunodominance hierarchy. These data show
      persistence of gammaherpesvirus type 68 alters the properties of CD8(+) T cells
      and illustrates that immune surveillance does not require CD8 T cells with the
      same attributes as "classical" memory CD8(+) T cells.

PMID- 16912283
TI  - Inducible yeast system for Viral RNA recombination reveals requirement for an RNA
      replication signal on both parental RNAs.
AB  - To facilitate RNA recombination studies, we tested whether Saccharomyces
      cerevisiae, which supports brome mosaic virus (BMV) replication, also supports
      BMV RNA recombination. Yeast strains expressing BMV RNA replication proteins 1a
      and 2a(pol) were engineered to transiently coexpress two independently inducible,
      overlapping, nonreplicating derivatives of BMV genomic RNA3. B3Delta3' lacked the
      coat protein gene and negative-strand RNA promoter. B3Delta5' lacked the positive
      strand RNA promoter and had the coat gene replaced by the selectable URA3 gene.
      After 12 to 72 h of induction, B3Delta3' and B3Delta5' transcription was
      repressed and Ura(+) yeast cells were selected. All Ura(+) cells contained
      recombinant RNA3 replicons expressing URA3. Most replicons arose by
      intermolecular homologous recombination between B3Delta3' and B3Delta5'. Such
      recombinants were isolated only when 1a and 2a(pol) were expressed and after
      transient transcription of both B3Delta3' and B3Delta5', showing that
      recombination occurred at the RNA, not DNA, level. A minority of URA3-expressing
      replicons were derived from B3Delta5', independently of B3Delta3', by 5'
      truncation and modification, generating novel positive-strand promoters and
      demonstrating that BMV can give rise to subgenomic RNA replicons. Intermolecular
      B3Delta3'-B3Delta5' recombination occurred only when both parental RNAs bore a
      functional, cis-acting template recognition and recruitment element targeting
      viral RNAs to replication complexes. The results imply that recombination
      occurred in RNA replication complexes to which parental RNAs were independently
      recruited. Moreover, the ability to obtain intermolecular recombinants at
      precisely measurable, reproducible frequencies, to control genetic background and
      induction conditions, and other features of this system will facilitate further
      studies of virus and host functions in RNA recombination.

PMID- 16912285
TI  - Analysis of genetic bottlenecks during horizontal transmission of Cucumber mosaic
      virus.
AB  - Genetic bottlenecks may occur in virus populations when only a few individuals
      are transferred horizontally from one host to another, or when a viral population
      moves systemically from the infection site. Genetic bottlenecks during the
      systemic movement of an RNA plant virus population were reported previously (H.
      Li and M. J. Roossinck, J. Virol. 78:10582-10587, 2004). In this study we
      mechanically inoculated an artificial population consisting of 12 restriction
      enzyme marker mutants of Cucumber mosaic virus (CMV) onto young leaves of squash
      plants and used two aphid species, Aphis gossypii and Myzus persicae, to transmit
      the virus populations from infected source plants to healthy squash plants.
      Horizontal transmission by aphids constituted a significant bottleneck, as the
      population in the aphid-inoculated plants contained far fewer mutants than the
      original inoculum source. Additional experiments demonstrated that genetic
      variation in the artificial population of CMV is not reduced during the
      acquisition of the virus but is significantly reduced during the inoculation
      period.

PMID- 16912284
TI  - Tobacco mosaic virus movement protein functions as a structural microtubule
      associated protein.
AB  - The cell-to-cell spread of Tobacco mosaic virus infection depends on virus
      encoded movement protein (MP), which is believed to form a ribonucleoprotein
      complex with viral RNA (vRNA) and to participate in the intercellular spread of
      infectious particles through plasmodesmata. Previous studies in our laboratory
      have provided evidence that the vRNA movement process is correlated with the
      ability of the MP to interact with microtubules, although the exact role of this
      interaction during infection is not known. Here, we have used a variety of in
      vivo and in vitro assays to determine that the MP functions as a genuine
      microtubule-associated protein that binds microtubules directly and modulates
      microtubule stability. We demonstrate that, unlike MP in whole-cell extract,
      microtubule-associated MP is not ubiquitinated, which strongly argues against the
      hypothesis that microtubules target the MP for degradation. In addition, we found
      that MP interferes with kinesin motor activity in vitro, suggesting that
      microtubule-associated MP may interfere with kinesin-driven transport processes
      during infection.

PMID- 16912286
TI  - Identification of protective Lassa virus epitopes that are restricted by HLA-A2.
AB  - Recovery from Lassa virus (LASV) infection usually precedes the appearance of
      neutralizing antibodies, indicating that cellular immunity plays a primary role
      in viral clearance. To date, the role of LASV-specific CD8(+) T cells has not
      been evaluated in humans. To facilitate such studies, we utilized a predictive
      algorithm to identify candidate HLA-A2 supertype epitopes from the LASV
      nucleoprotein and glycoprotein precursor (GPC) genes. We identified three
      peptides (GPC(42-50), GLVGLVTFL; GPC(60-68), SLYKGVYEL; and GPC(441-449),
      YLISIFLHL) that displayed high-affinity binding (< or =98 nM) to HLA-A*0201,
      induced CD8(+) T-cell responses of high functional avidity in HLA-A*0201
      transgenic mice, and were naturally processed from native LASV GPC in human HLA
      A*0201-positive target cells. HLA-A*0201 mice immunized with either GPC(42-50) or
      GPC(60-68) were protected against challenge with a recombinant vaccinia virus
      that expressed LASV GPC. The epitopes identified in this study represent
      potential diagnostic reagents and candidates for inclusion in epitope-based
      vaccine constructs. Our approach is applicable to any pathogen with existing
      sequence data, does not require manipulation of the actual pathogen or access to
      immune human donors, and should therefore be generally applicable to category A
      through C agents and other emerging pathogens.

PMID- 16912287
TI  - West Nile virus 5'-cap structure is formed by sequential guanine N-7 and ribose
      2'-O methylations by nonstructural protein 5.
AB  - Many flaviviruses are globally important human pathogens. Their plus-strand RNA
      genome contains a 5'-cap structure that is methylated at the guanine N-7 and the
      ribose 2'-OH positions of the first transcribed nucleotide, adenine (m(7)GpppAm).
      Using West Nile virus (WNV), we demonstrate, for the first time, that the
      nonstructural protein 5 (NS5) mediates both guanine N-7 and ribose 2'-O
      methylations and therefore is essential for flavivirus 5'-cap formation. We show
      that a recombinant full-length and a truncated NS5 protein containing the
      methyltransferase (MTase) domain methylates GpppA-capped and m(7)GpppA-capped
      RNAs to m(7)GpppAm-RNA, using S-adenosylmethionine as a methyl donor.
      Furthermore, methylation of GpppA-capped RNA sequentially yielded m(7)GpppA- and
      m(7)GpppAm-RNA products, indicating that guanine N-7 precedes ribose 2'-O
      methylation. Mutagenesis of a K(61)-D(146)-K(182)-E(218) tetrad conserved in
      other cellular and viral MTases suggests that NS5 requires distinct amino acids
      for its N-7 and 2'-O MTase activities. The entire K(61)-D(146)-K(182)-E(218)
      motif is essential for 2'-O MTase activity, whereas N-7 MTase activity requires
      only D(146). The other three amino acids facilitate, but are not essential for,
      guanine N-7 methylation. Amino acid substitutions within the K(61)-D(146)-K(182)
      E(218) motif in a WNV luciferase-reporting replicon significantly reduced or
      abolished viral replication in cells. Additionally, the mutant MTase-mediated
      replication defect could not be trans complemented by a wild-type replicase
      complex. These findings demonstrate a critical role for the flavivirus MTase in
      viral reproduction and underscore this domain as a potential target for antiviral
      therapy.

PMID- 16912288
TI  - Human cytomegalovirus pUS24 is a virion protein that functions very early in the
      replication cycle.
AB  - We have characterized the function of the human cytomegalovirus US24 gene, a US22
      gene family member. Two US24-deficient mutants (BADinUS24 and BADsubUS24)
      exhibited a 20- to 30-fold growth defect, compared to their wild-type parent
      (BADwt), after infection at a relatively low (0.01 PFU/cell) or high (1 PFU/cell)
      input multiplicity. Representative virus-encoded proteins and viral DNA
      accumulated with normal kinetics to wild-type levels after infection with mutant
      virus when cells received equal numbers of mutant and wild-type infectious units.
      Further, the proteins were properly localized and no ultrastructural differences
      were found by electron microscopy in mutant-virus-infected cells compared to wild
      type-virus-infected cells. However, virions produced by US24-deficient mutants
      had a 10-fold-higher genome-to-PFU ratio than wild-type virus. When infections
      were performed using equal numbers of input virus particles, the expression of
      immediate-early, early, and late viral proteins was substantially delayed and
      decreased in the absence of US24 protein. This delay is not due to inefficient
      virus entry, since two tegument proteins and viral DNA moved to the nucleus
      equally well in mutant- and wild-type-virus-infected cells. In summary, US24 is a
      virion protein and virions produced by US24-deficient viruses exhibit a block to
      the human cytomegalovirus replication cycle after viral DNA reaches the nucleus
      and before immediate-early mRNAs are transcribed.

PMID- 16912289
TI  - Crystal structure of the moloney murine leukemia virus RNase H domain.
AB  - A crystallographic study of the Moloney murine leukemia virus (Mo-MLV) RNase H
      domain was performed to provide information about its structure and mechanism of
      action. These efforts resulted in the crystallization of a mutant Mo-MLV RNase H
      lacking the putative helix C (DeltaC). The 1.6-Angstroms resolution structure
      resembles the known structures of the human immunodeficiency virus type 1 (HIV-1)
      and Escherichia coli RNase H. The structure revealed the coordination of a
      magnesium ion within the catalytic core comprised of the highly conserved acidic
      residues D524, E562, and D583. Surface charge mapping of the Mo-MLV structure
      revealed a high density of basic charges on one side of the enzyme. Using a model
      of the Mo-MLV structure superimposed upon a structure of HIV-1 reverse
      transcriptase bound to an RNA/DNA hybrid substrate, Mo-MLV RNase H secondary
      structures and individual amino acids were examined for their potential roles in
      binding substrate. Identified regions included Mo-MLV RNase H beta1-beta2,
      alphaA, and alphaB and residues from alphaB to alphaD and its following loop.
      Most of the identified substrate-binding residues corresponded with residues
      directly binding nucleotides in an RNase H from Bacillus halodurans as observed
      in a cocrystal structure with RNA/DNA. Finally, superimposition of RNases H of Mo
      MLV, E. coli, and HIV-1 revealed that a loop of the HIV-1 connection domain
      resides within the same region of the Mo-MLV and E. coli C-helix. The HIV-1
      connection domain may serve to recognize and bind the RNA/DNA substrate major
      groove.

PMID- 16912290
TI  - Potential role for p53 in the permissive life cycle of human cytomegalovirus.
AB  - Infection of primary fibroblasts with human cytomegalovirus (HCMV) causes a rapid
      stabilization of the cellular protein p53. p53 is a major effector of the
      cellular damage response, and activation of this transcription factor can lead
      either to cell cycle arrest or to apoptosis. Viruses employ many tactics to avoid
      p53-mediated effects. One method HCMV uses to counteract p53 is sequestration
      into its viral replication centers. In order to determine whether or not HCMV
      benefits from this sequestration, we infected a p53(-/-) fibroblast line. We find
      that although these cells are permissive for viral infection, several parameters
      are substantially altered compared to wild-type (wt) fibroblasts. p53(-/-) cells
      show delayed and decreased accumulation of infectious viral particles compared to
      control fibroblasts, with the largest difference of 100-fold at 72 h post
      infection (p.i.) and peak titers decreased by approximately 10- to 20-fold at 144
      h p.i. Viral DNA accumulation is also delayed and somewhat decreased in p53(-/-)
      cells; however, on average, levels of DNA are not more than fivefold lower than
      wt at any time p.i. and thus cannot account entirely for the observed differences
      in titers. In addition, there are delays in the expression of several key viral
      proteins, including the early replication protein UL44 and some of the late
      structural proteins, pp28 (UL99) and MCP (UL86). UL44 localization also indicates
      delayed formation and maturation of the replication centers throughout the course
      of infection. Localization of the major tegument protein pp65 (UL83) is also
      altered in these p53(-/-) cells. Partial reconstitution of the p53(-/-) cells
      with a wt copy of p53 returns all parameters toward wt, while reconstitution with
      mutant p53 does not. Taken together, our data suggest that wt p53 enhances the
      ability of HCMV to replicate and produce high concentrations of infectious
      virions in permissive cells.

PMID- 16912291
TI  - The envelope G3L protein is essential for entry of vaccinia virus into host
      cells.
AB  - The vaccinia virus G3L/WR079 gene encodes a conserved protein with a predicted
      transmembrane domain. Our proteomic analyses of vaccinia virus revealed that G3L
      protein is incorporated into intracellular mature virus; however, the function of
      G3L protein in the vaccinia virus life cycle has not been investigated. In this
      study, a recombinant vaccinia virus, viG3L, expressing G3L protein under IPTG
      (isopropyl-beta-d-thiogalactopyranoside) regulation was constructed. Under
      permissive conditions when G3L protein was expressed, the vaccinia virus life
      cycle proceeded normally, resulting in plaque formation in BSC40 cells. In
      contrast, under nonpermissive conditions when G3L protein expression was
      repressed, no plaques were formed, showing that G3L protein is essential for
      vaccinia virus growth in cell cultures. In infected cells when G3L protein was
      not expressed, the formation of intracellular mature virus (IMV) and cell
      associated enveloped virus occurred normally, showing that G3L protein is not
      required for virion morphogenesis. IMV particles containing (G3L(+)) or lacking
      (G3L(-)) G3L protein were purified and were found to be indistinguishable on
      microscopic examination. Both G3L(+) and G3L(-) IMV bound to HeLa cells; however,
      G3L(-) IMV failed to enter the cells, showing that G3L protein is required for
      IMV penetration into cells. Finally, G3L protein was required for fusion of the
      infected cells under low-pH treatment. Thus, our results provide direct evidence
      that G3L is an essential component of the vaccinia virus fusion complex, in
      addition to the previously reported A28, H2, L5, A21, and A16 proteins.

PMID- 16912292
TI  - Mutational pathways, resistance profile, and side effects of cyanovirin relative
      to human immunodeficiency virus type 1 strains with N-glycan deletions in their
      gp120 envelopes.
AB  - Limited data are available on the genotypic and phenotypic resistance profile of
      the alpha-(1-2)mannose oligomer-specific prokaryotic lectin cyanovirin (CV-N).
      Therefore, a more systematic investigation was carried out to obtain a better
      view of the interaction between CV-N and human immunodeficiency virus type 1 (HIV
      1) gp120. When HIV-1-infected CEM cell cultures were exposed to CV-N in a dose
      escalating manner, a total of eight different amino acid mutations exclusively
      located at N-glycosylation sites in the envelope surface gp120 were observed. Six
      of the eight mutations resulted in the deletion of high-mannose type N-glycans
      (i.e., at amino acid positions 230, 332, 339, 386, 392, and 448). Two mutations
      (i.e., at position 136 and 160) deleted a complex type N-glycan in the variable
      V1/V2 domain of gp120. The level of phenotypic resistance of the mutated virus
      strains against CV-N generally correlated with the number of glycan deletions in
      gp120, although deletion of the glycans at N-230, N-392, and N-448 generally
      afforded a more pronounced CV-N resistance than other N-glycan deletions.
      However, the extent of the decrease of antiviral activity of CV-N against the
      mutated virus strains was markedly less pronounced than observed for alpha(1-3)-
      and alpha(1-6)-mannose-specific plant lectins Hippeastrum hybrid agglutinin (HHA)
      and Galanthus nivalis agglutinin (GNA), which points to the existence of a higher
      genetic barrier for CV-N. This is in agreement with a more consistent suppression
      of a wider variety of HIV-1 clades by CV-N than by HHA and GNA. Whereas the
      antiviral and in vitro antiproliferative activity of CV-N can be efficiently
      reversed by mannan, the pronounced mitogenic activity of CV-N on peripheral blood
      mononuclear cells was unaffected by mannan, indicating that some of the observed
      side effects of CV-N are unrelated to its carbohydrate specificity/activity.

PMID- 16912293
TI  - Reovirus outer capsid protein micro1 induces apoptosis and associates with lipid
      droplets, endoplasmic reticulum, and mitochondria.
AB  - The mechanisms by which reoviruses induce apoptosis have not been fully
      elucidated. Earlier studies identified the mammalian reovirus S1 and M2 genes as
      determinants of apoptosis induction. However, no published results have
      demonstrated the capacities of the proteins encoded by these genes to induce
      apoptosis, either independently or in combination, in the absence of reovirus
      infection. Here we report that the mammalian reovirus micro1 protein, encoded by
      the M2 gene, was sufficient to induce apoptosis in transfected cells. We also
      found that micro1 localized to lipid droplets, endoplasmic reticulum, and
      mitochondria in both transfected cells and infected cells. Two small regions
      encompassing amphipathic alpha-helices within a carboxyl-terminal portion of
      micro1 were necessary for efficient induction of apoptosis and association with
      lipid droplets, endoplasmic reticulum, and mitochondria in transfected cells.
      Induction of apoptosis by micro1 and its association with lipid droplets and
      intracellular membranes in transfected cells were abrogated when micro1 was
      coexpressed with sigma3, with which it is known to coassemble. We propose that
      micro1 plays a direct role in the induction of apoptosis in infected cells and
      that this property may relate to the capacity of micro1 to associate with
      intracellular membranes. Moreover, during reovirus infection, association with
      sigma3 may regulate apoptosis induction by micro1.

PMID- 16912294
TI  - Genome of invertebrate iridescent virus type 3 (mosquito iridescent virus).
AB  - Iridoviruses (IVs) are classified into five genera: Iridovirus and
      Chloriridovirus, whose members infect invertebrates, and Ranavirus,
      Lymphocystivirus, and Megalocytivirus, whose members infect vertebrates. Until
      now, Chloriridovirus was the only IV genus for which a representative and
      complete genomic sequence was not available. Here, we report the genome sequence
      and comparative analysis of a field isolate of Invertebrate iridescent virus type
      3 (IIV-3), also known as mosquito iridescent virus, currently the sole member of
      the genus Chloriridovirus. Approximately 20% of the 190-kbp IIV-3 genome was
      repetitive DNA, with DNA repeats localized in 15 apparently noncoding regions. Of
      the 126 predicted IIV-3 genes, 27 had homologues in all currently sequenced IVs,
      suggesting a genetic core for the family Iridoviridae. Fifty-two IIV-3 genes,
      including those encoding DNA topoisomerase II, NAD-dependent DNA ligase, SF1
      helicase, IAP, and BRO protein, are present in IIV-6 (Chilo iridescent virus,
      prototype species of the genus Iridovirus) but not in vertebrate IVs, likely
      reflecting distinct evolutionary histories for vertebrate and invertebrate IVs
      and potentially indicative of genes that function in aspects of virus
      invertebrate host interactions. Thirty-three IIV-3 genes lack homologues in other
      IVs. Most of these encode proteins of unknown function but also encode IIV3-053L,
      a protein with similarity to DNA-dependent RNA polymerase subunit 7; IIV3-044L, a
      putative serine/threonine protein kinase; and IIV3-080R, a protein with
      similarity to poxvirus MutT-like proteins. The absence of genes present in other
      IVs, including IIV-6; the lack of obvious colinearity with any sequenced IV; the
      low levels of amino acid identity of predicted proteins to IV homologues; and
      phylogenetic analyses of conserved proteins indicate that IIV-3 is distantly
      related to other IV genera.

PMID- 16912295
TI  - Antiviral potency of APOBEC proteins does not correlate with cytidine
      deamination.
AB  - The human cytidine deaminases APOBEC3G (hA3G) and APOBEC3F (hA3F) are
      intracellular antiretroviral factors that can hypermutate nascent reverse
      transcripts and inhibit the replication of human immunodeficiency virus type 1
      (HIV-1). Both enzymes have two cytidine deaminase motifs, although only the C
      terminal motif is catalytic. Current models of APOBEC protein function imply
      editing is the principal mechanism of antiviral activity. In particular, hA3G is
      a more potent inhibitor of HIV-1 infectivity than hA3F and also induces a greater
      frequency of mutations in HIV-1 cDNA. We used hA3G/hA3F chimeric proteins to
      investigate whether cytidine deaminase potential reflects antiviral potency. We
      show here that the origin of the C-terminal deaminase motif is sufficient to
      determine the degree of mutation induced in a bacterial assay that measures
      mutations in chromosomal DNA. In contrast, this was not the case in the context
      of HIV-1 infection where the N-terminal deaminase motif also modulated the
      editing capabilities of the chimeras. Surprisingly, although three of the
      chimeric proteins induced levels of mutation that approximated those of parental
      hA3F, they displayed lower levels of antiviral activity. Most importantly, real
      time PCR experiments revealed that the quantity of reverse transcripts detected
      in target cells, rather than the mutational burden carried by such DNAs,
      corresponded closely with viral infectivity. In other words, the antiviral
      phenotype of APOBEC proteins correlates with their ability to prevent the
      accumulation of reverse transcripts and not with the induction of hypermutation.

PMID- 16912296
TI  - Membrane-bound tomato mosaic virus replication proteins participate in RNA
      synthesis and are associated with host proteins in a pattern distinct from those
      that are not membrane bound.
AB  - Extracts of vacuole-depleted, tomato mosaic virus (ToMV)-infected plant
      protoplasts contained an RNA-dependent RNA polymerase (RdRp) that utilized an
      endogenous template to synthesize ToMV-related positive-strand RNAs in a pattern
      similar to that observed in vivo. Despite the fact that only minor fractions of
      the ToMV 130- and 180-kDa replication proteins were associated with membranes,
      the RdRp activity was exclusively associated with membranes. A genome-sized,
      negative-strand RNA template was associated with membranes and was resistant to
      micrococcal nuclease unless treated with detergents. Non-membrane-bound
      replication proteins did not exhibit RdRp activity, even in the presence of ToMV
      RNA. While the non-membrane-bound replication proteins remained soluble after
      treatment with Triton X-100, the same treatment made the membrane-bound
      replication proteins in a form that precipitated upon low-speed centrifugation.
      On the other hand, the detergent lysophosphatidylcholine (LPC) efficiently
      solubilized the membrane-bound replication proteins. Upon LPC treatment, the
      endogenous template-dependent RdRp activity was reduced and exogenous ToMV RNA
      template-dependent RdRp activity appeared instead. This activity, as well as the
      viral 130-kDa protein and the host proteins Hsp70, eukaryotic translation
      elongation factor 1A (eEF1A), TOM1, and TOM2A copurified with FLAG-tagged viral
      180-kDa protein from LPC-solubilized membranes. In contrast, Hsp70 and only small
      amounts of the 130-kDa protein and eEF1A copurified with FLAG-tagged non-membrane
      bound 180-kDa protein. These results suggest that the viral replication proteins
      are associated with the intracellular membranes harboring TOM1 and TOM2A and that
      this association is important for RdRp activity. Self-association of the viral
      replication proteins and their association with other host proteins may also be
      important for RdRp activity.

PMID- 16912297
TI  - Differences and similarities in viral life cycle progression and host cell
      physiology after infection of human dendritic cells with modified vaccinia virus
      Ankara and vaccinia virus.
AB  - Modified vaccinia virus Ankara (MVA) is an attenuated strain of vaccinia virus
      (VV) that has attracted significant attention as a candidate viral vector vaccine
      for immunization against infectious diseases and treatment of malignancies.
      Although MVA is unable to replicate in most nonavian cells, vaccination with MVA
      elicits immune responses that approximate those seen after the administration of
      replication-competent strains of VV. However, the mechanisms by which these
      viruses elicit immune responses and the determinants of their relative
      immunogenicity are incompletely understood. Studying the interactions of VV and
      MVA with cells of the human immune system may elucidate these mechanisms, as well
      as provide a rational basis for the further enhancement of the immunogenicity of
      recombinant MVA vectors. Toward this end, we investigated the consequences of MVA
      or VV infection of human dendritic cells (DCs), key professional antigen
      presenting cells essential for the generation of immune responses. We determined
      that a block to the formation of intracellular viral replication centers results
      in abortive infection of DCs with both VV and MVA. MVA inhibited cellular protein
      synthesis more rapidly than VV and displayed a distinct pattern of viral protein
      expression in infected DCs. MVA also induced apoptosis in DCs more rapidly than
      VV, and DC apoptosis after MVA infection was associated with an accelerated
      decline in the levels of intracellular Bcl-2 and Bcl-X(L). These findings suggest
      that antigen presentation pathways may contribute differentially to the
      immunogenicity of VV and MVA and that targeted modifications of virus-induced DC
      apoptosis may further increase the immunogenicity of MVA-vectored vaccines.

PMID- 16912298
TI  - Purified feline and canine transferrin receptors reveal complex interactions with
      the capsids of canine and feline parvoviruses that correspond to their host
      ranges.
AB  - The cell infection processes and host ranges of canine parvovirus (CPV) and
      feline panleukopenia virus (FPV) are controlled by their capsid interactions with
      the transferrin receptors (TfR) on their host cells. Here, we expressed the
      ectodomains of wild-type and mutant TfR and tested those for binding to purified
      viral capsids and showed that different naturally variant strains of the viruses
      were associated with variant interactions with the receptors which likely reflect
      the optimization of the viral infection processes in the different hosts. While
      all viruses bound the feline TfR, reflecting their tissue culture host ranges, a
      naturally variant mutant of CPV (represented by the CPV type-2b strain) that
      became the dominant virus worldwide in 1979 showed significantly lower levels of
      binding to the feline TfR. The canine TfR ectodomain did not bind to a detectable
      level in the in vitro assays, but this appears to reflect the naturally low
      affinity of that interaction, as only low levels of binding were seen when the
      receptor was expressed on mammalian cells; however, that was sufficient to allow
      endocytosis and infection. The apical domain of the canine TfR controls the
      specific interaction with CPV capsids, as a canine TfR mutant altering a
      glycosylation site in that domain bound FPV, CPV-2, and CPV-2b capsids
      efficiently. Enzymatic removal of the N-linked glycans did not allow FPV binding
      to the canine TfR, suggesting that the protein sequence difference is itself
      important. The purified feline TfR inhibited FPV and CPV-2 binding and infection
      of feline cells but not CPV-2b, indicating that the receptor binding may be able
      to prevent the attachment to the same receptor on cells.

PMID- 16912299
TI  - Structural and functional basis for ADP-ribose and poly(ADP-ribose) binding by
      viral macro domains.
AB  - Macro domains constitute a protein module family found associated with specific
      histones and proteins involved in chromatin metabolism. In addition, a small
      number of animal RNA viruses, such as corona- and toroviruses, alphaviruses, and
      hepatitis E virus, encode macro domains for which, however, structural and
      functional information is extremely limited. Here, we characterized the macro
      domains from hepatitis E virus, Semliki Forest virus, and severe acute
      respiratory syndrome coronavirus (SARS-CoV). The crystal structure of the SARS
      CoV macro domain was determined at 1.8-Angstroms resolution in complex with ADP
      ribose. Information derived from structural, mutational, and sequence analyses
      suggests a close phylogenetic and, most probably, functional relationship between
      viral and cellular macro domain homologs. The data revealed that viral macro
      domains have relatively poor ADP-ribose 1"-phosphohydrolase activities (which
      were previously proposed to be their biologically relevant function) but bind
      efficiently free and poly(ADP-ribose) polymerase 1-bound poly(ADP-ribose) in
      vitro. Collectively, these results suggest to further evaluate the role of viral
      macro domains in host response to viral infection.

PMID- 16912300
TI  - Phylogenetic analysis reveals a correlation between the expansion of very
      virulent infectious bursal disease virus and reassortment of its genome segment
      B.
AB  - Infectious bursal disease virus (IBDV) is a birnavirus causing immunosuppressive
      disease in chickens. Emergence of the very virulent form of IBDV (vvIBDV) in the
      late 1980s dramatically changed the epidemiology of the disease. In this study,
      we investigated the phylogenetic origins of its genome segments and estimated the
      time of emergence of their most recent common ancestors. Moreover, with recently
      developed coalescence techniques, we reconstructed the past population dynamics
      of vvIBDV and timed the onset of its expansion to the late 1980s. Our analysis
      suggests that genome segment A of vvIBDV emerged at least 20 years before its
      expansion, which argues against the hypothesis that mutation of genome segment A
      is the major contributing factor in the emergence and expansion of vvIBDV.
      Alternatively, the phylogeny of genome segment B suggests a possible reassortment
      event estimated to have taken place around the mid-1980s, which seems to coincide
      with its expansion within approximately 5 years. We therefore hypothesize that
      the reassortment of genome segment B initiated vvIBDV expansion in the late
      1980s, possibly by enhancing the virulence of the virus synergistically with its
      existing genome segment A. This report reveals the possible mechanisms leading to
      the emergence and expansion of vvIBDV, which would certainly provide insights
      into the scope of surveillance and prevention efforts regarding the disease.

PMID- 16912302
TI  - The charge structure of helix 1 in the prion protein regulates conversion to
      pathogenic PrPSc.
AB  - The prion diseases are transmissible neurodegenerative disorders linked to a
      pathogenic conformer (PrP(Sc)) of the normal prion protein (PrP(C)). Accumulation
      of PrP(Sc) occurs via a poorly defined process in which PrP(Sc) complexes with
      and converts endogenous PrP(C) to nascent PrP(Sc). Recent experiments have
      focused on the highly charged first alpha helix (H1) of PrP. It has been proposed
      that two putative asparagine-to-arginine intrahelical salt bridges stabilize H1
      in PrP(C) yet form intermolecular ionic bonds with adjacent PrP molecules during
      conversion of PrP(C) to PrP(Sc) (M. P. Morrissey and E. I. Shakhnovich, Proc.
      Natl. Acad. Sci. USA 96:11293-11298, 1999). Subsequent work (J. O. Speare et al.,
      J. Biol. Chem. 278:12522-12529, 2003 using a cell-free assay of PrP(Sc)
      conversion suggested that rather than promoting conversion, the salt bridges
      stabilize PrP(C) against it. However, the role of individual H1 charges in
      PrP(Sc) generation has not yet been investigated. To approach this question, we
      systematically reversed or neutralized each charged residue in H1 and tested the
      effect on conversion to PrP(Sc) in scrapie-infected murine neuroblastoma (ScN2a)
      cells. We find that replacements of charged H1 residues with like charges permit
      conversion, while charge reversals hinder it. Neutralization of charges in the N
      terminal (amino acids 143 to 146) but not the C-terminal (amino acids 147 to 151)
      half of H1 permits conversion, while complete reversal of charge orientation of
      the putative salt bridges produces a nonconvertible PrP. Circular dichroism
      spectroscopy studies and confocal microscopy immunofluorescence localization
      studies indicated that charge substitutions did not alter the secondary structure
      or cell surface expression of PrP(C). These data support the necessity of
      specific charge orientations in H1 for a productive PrP(Sc)-PrP(C) complex.

PMID- 16912301
TI  - Abrogation of viral interleukin-6 (vIL-6)-induced signaling by intracellular
      retention and neutralization of vIL-6 with an anti-vIL-6 single-chain antibody
      selected by phage display.
AB  - Human herpesvirus 8 (HHV-8) encodes several putative oncogenes, which are
      homologues to cellular host genes known to function in cell cycle regulation,
      control of apoptosis, and cytokine signaling. Viral interleukin (vIL-6) is
      believed to play an important role in the pathogenesis of Kaposi's sarcoma as
      well as primary effusion lymphoma and multicentric Castleman's disease.
      Therefore, vIL-6 is a promising target for novel therapies directed against HHV-8
      associated diseases. By phage display screening of human synthetic antibody
      libraries, we have selected a specific recombinant antibody, called monoclonal
      anti-vIL-6 (MAV), binding to vIL-6. The epitope recognized by MAV was localized
      on the top of the D helix of the vIL-6 protein, which is a part of receptor
      binding site III. Consequently, MAV specifically inhibits vIL-6-mediated growth
      of the primary effusion lymphoma-derived cell line BCBL-1 and blocks STAT3
      phosphorylation in the human hepatoma cell line HepG2. Since it was previously
      found that vIL-6 can also induce signals from within the cell, presumably within
      the endoplasmic reticulum, we fused the recombinant antibody MAV with the
      endoplasmic retention sequence KDEL (MAV-KDEL). As a result, COS-7 cells
      expressing MAV-KDEL and synthesizing vIL-6 ceased to secrete the cytokine.
      Moreover, we observed that vIL-6 that was bound to MAV-KDEL and retained in the
      endoplasmic reticulum did not induce STAT3 phosphorylation in HepG2 cells. We
      conclude that the activity of the intracellularly retained vIL-6 protein is
      neutralized by MAV-KDEL. Our results might represent a novel therapeutic strategy
      to neutralize virally encoded growth factors or oncogenes.

PMID- 16912303
TI  - Immunoglobulin g antibody-mediated enhancement of measles virus infection can
      bypass the protective antiviral immune response.
AB  - Antibodies to viral surface glycoproteins play a crucial role in immunity to
      measles by blocking both virus attachment and subsequent fusion with the host
      cell membrane. Here, we demonstrate that certain immunoglobulin G (IgG)
      antibodies can also enhance the entry of measles virus (MV) into monocytes and
      macrophages. Antibody-dependent enhancement of infectivity was observed in mouse
      and human macrophages using virions opsonized by a murine monoclonal antibody
      against the MV hemagglutinin (H) glycoprotein, polyclonal mouse anti-MV IgG, or
      diluted measles-immune human sera. Neither H-specific Fab fragments nor H
      specific IgM could enhance MV entry in monocytes or macrophages, indicating
      involvement of a Fc gamma receptor (FcgammaR)-mediated mechanism. Preincubation
      with an anti-fusion protein (anti-F) monoclonal antibody or a fusion-inhibitory
      peptide blocked infection, indicating that a functional F protein was required
      for viral internalization. Classical complement pathway activation did not
      promote infection through complement receptors and inhibited anti-H IgG-mediated
      enhancement. In vivo, antibody-enhanced infection allowed MV to overcome a highly
      protective systemic immune response in preimmunized IfnarKo-Ge46 transgenic mice.
      These data demonstrate a previously unidentified mechanism that may contribute to
      morbillivirus pathogenesis where H-specific IgG antibodies promote the spread of
      MV infection among FcgammaR-expressing host cells. The findings point to a new
      model for the pathogenesis of atypical MV infection observed after immunization
      with formalin-inactivated MV vaccine and underscore the importance of the anti-F
      response after vaccination.

PMID- 16912304
TI  - Inhibition by woodchuck hepatitis virus of class I major histocompatibility
      complex presentation on hepatocytes is mediated by virus envelope pre-S2 protein
      and can be reversed by treatment with gamma interferon.
AB  - Presentation of class I major histocompatibility complex (MHC) is severely down
      regulated on hepatocytes in chronic hepatitis caused by woodchuck hepatitis virus
      (WHV). To determine which of the viral proteins mediates class I MHC antigen
      suppression, cultured normal woodchuck hepatocytes were transfected with the
      complete WHV genome, sequences encoding individual virus proteins, or whole virus
      genomes in which transcription of selected proteins was disabled by site-specific
      mutagenesis. It was found that hepatocyte presentation of class I MHC antigen was
      significantly inhibited following transfection with complete WHV genome or with
      viral subgenomic fragments encoding envelope pre-S2 protein or pre-S1 protein,
      which naturally encompasses pre-S2 amino acid sequence. In contrast, hepatocytes
      transfected with WHV X gene alone demonstrated a profound enhancement in the
      class I antigen display, whereas those expressing virus major S protein or
      nucleocapsid (core) protein were not different from control hepatocytes. Analysis
      of the mutated WHV sequences confirmed that the envelope pre-S2 protein was
      responsible for inhibition of the class I MHC antigen display. Interestingly,
      treatment with recombinant woodchuck gamma interferon (rwIFN-gamma) restored the
      inhibited presentation of the class I antigen. Moreover, the class I antigen
      suppression was not associated with down-regulation of hepatocyte genes for class
      I MHC heavy chain, beta(2)-microglobulin, transporters associated with antigen
      processing, and proteasome subunits. These findings indicate that the defective
      presentation of class I MHC antigen on hepatocytes transcribing WHV is a
      consequence of posttranscriptional suppression exerted by virus pre-S2 protein
      and that this hindrance can be fully reversed by IFN-gamma.

PMID- 16912305
TI  - All three variable regions of the TRIM5alpha B30.2 domain can contribute to the
      specificity of retrovirus restriction.
AB  - Recent studies have revealed the contribution of TRIM5alpha to retrovirus
      restriction in cells from a variety of primate species. TRIM5alpha consists of a
      tripartite motif (the RBCC domain) followed by a B30.2 domain. The B30.2 domain
      is thought to be involved in determination of restriction specificity and
      contains three variable regions. To investigate the relationship between the
      phylogeny of primate TRIM5alpha and retrovirus restriction specificity, a series
      of chimeric TRIM5alpha consisting of the human RBCC domain followed by the B30.2
      domain from various primates was constructed. These constructs showed restriction
      profiles largely consistent with the origin of the B30.2 domain. Restriction
      specificity was further investigated with a variety of TRIM5alphas containing
      mixed or mutated B30.2 domains. This study revealed the importance of all three
      variable regions for determining restriction specificity. Based on the molecular
      structures of other PRYSPRY domains solved recently, a model for the molecular
      structure of the B30.2 domain of TRIM5alpha was developed. The model revealed
      that the variable regions of the B30.2 domain are present as loops located on one
      side of the B30.2 core structure. It is hypothesized that these three loops form
      a binding surface for virus and that evolutionary changes in any one of the loops
      can alter restriction specificity.

PMID- 16912306
TI  - Tertiary structural and functional analyses of a viroid RNA motif by isostericity
      matrix and mutagenesis reveal its essential role in replication.
AB  - RNA-templated RNA replication is essential for viral or viroid infection, as well
      as for regulation of cellular gene expression. Specific RNA motifs likely
      regulate various aspects of this replication. Viroids of the Pospiviroidae
      family, as represented by the Potato spindle tuber viroid (PSTVd), replicate in
      the nucleus by utilizing DNA-dependent RNA polymerase II. We investigated the
      role of the loop E (sarcin/ricin) motif of the PSTVd genomic RNA in replication.
      A tertiary-structural model of this motif, inferred by comparative sequence
      analysis and comparison with nuclear magnetic resonance and X-ray crystal
      structures of loop E motifs in other RNAs, is presented in which core non-Watson
      Crick base pairs are precisely specified. Isostericity matrix analysis of these
      base pairs showed that the model accounts for the reported natural sequence
      variations and viable experimental mutations in loop E motifs of PSTVd and other
      viroids. Furthermore, isostericity matrix analysis allowed us to design
      disruptive, as well as compensatory, mutations of PSTVd loop E. Functional
      analyses of such mutants by in vitro and in vivo experiments demonstrated that
      loop E structural integrity is crucial for replication, specifically during
      transcription. Our results suggest that the PSTVd loop E motif exists and
      functions in vivo and provide loss-of-function genetic evidence for the essential
      role of a viroid RNA three-dimensional motif in rolling-circle replication. The
      use of isostericity matrix analysis of non-Watson-Crick base pairing to
      rationalize mutagenesis of tertiary motifs and systematic in vitro and in vivo
      functional assays of mutants offers a novel, comprehensive approach to elucidate
      the tertiary-structure-function relationships for RNA motifs of general
      biological significance.

PMID- 16912307
TI  - Cross talk between PML and p53 during poliovirus infection: implications for
      antiviral defense.
AB  - PML nuclear bodies (NBs) are dynamic intranuclear structures harboring numerous
      transiently or permanently localized proteins. PML, the NBs' organizer, is
      directly induced by interferon, and its expression is critical for antiviral host
      defense. We describe herein the molecular events following poliovirus infection
      that lead to PML-dependent p53 activation and protection against virus infection.
      Poliovirus infection induces PML phosphorylation through the extracellular signal
      regulated kinase pathway, increases PML SUMOylation, and induces its transfer
      from the nucleoplasm to the nuclear matrix. These events result in the
      recruitment of p53 to PML NBs, p53 phosphorylation on Ser15, and activation of
      p53 target genes leading to the induction of apoptosis. Moreover, the knock-down
      of p53 by small interfering RNA results in higher poliovirus replication,
      suggesting that p53 participates in antiviral defense. This effect, which
      requires the presence of PML, is transient since poliovirus targets p53 by
      inducing its degradation in a proteasome- and MDM2-dependent manner. Our results
      provide evidence of how poliovirus counteracts p53 antiviral activity by
      regulating PML and NBs, thus leading to p53 degradation.

PMID- 16912308
TI  - The spread of Rice dwarf virus among cells of its insect vector exploits virus
      induced tubular structures.
AB  - Various cytopathological structures, known as inclusion bodies, are formed upon
      infection of cultured leafhopper cells by Rice dwarf virus, a member of the
      family Reoviridae. These structures include tubules of approximately 85 nm in
      diameter which are composed of the nonstructural viral protein Pns10 and contain
      viral particles. Such tubular structures were produced in heterologous non-host
      insect cells that expressed Pns10 of the virus. These tubules, when associated
      with actin-based filopodia, were able to protrude from the surface of cells and
      to penetrate neighboring cells. A binding assay in vitro revealed the specific
      binding of Pns10 to actin. Infection of clusters of cells was readily apparent 5
      days after inoculation at a low multiplicity of infection with the virus, even in
      the presence of neutralizing antibodies. However, treatment of host cells with
      drugs that inhibited the elongation of actin filaments abolished the extension of
      Pns10 tubules from the surface of cells, with a significant simultaneous decrease
      in the extent of infection of neighboring cells. These results together revealed
      a previously undescribed aspect of the intercellular spread of Rice dwarf virus,
      wherein the virus exploits tubules composed of a nonstructural viral protein and
      actin-based filopodia to move into neighboring cells.

PMID- 16912309
TI  - Rapid adaptation of a recombinant vesicular stomatitis virus to a targeted cell
      line.
AB  - Vesicular stomatitis virus (VSV) is being developed for cancer therapy. We
      created a recombinant replicating VSV (rrVSV) that preferentially infected
      Her2/neu-expressing breast cancer cells. This rrVSV did not express the native
      VSV-G glycoprotein (gp). Instead, it expressed a chimeric Sindbis gp which
      included a single-chain antibody (SCA) directed to the human Her2/neu receptor.
      The virus infected mouse mammary carcinoma cells (D2F2/E2) expressing Her2/neu 23
      fold better than the parent cells (D2F2). However, viral growth in cultured
      D2F2/E2 cells was curtailed after several cycles, and viral yield was very poor
      at 2 x 10(4) infectious doses (ID)/ml. We performed in vitro serial passage in
      D2F2/E2 cells to evolve a virus with improved growth that could be used for
      preclinical therapy trials in mice. Fifteen passes generated an adapted virus
      that progressed through multiple cycles in cultured D2F2/E2 cells until all cells
      were infected and had a viral yield of 1 x 10(8) ID/ml. Sequencing of the entire
      viral genomes found only 2 mutations in the adapted virus. Both mutations
      occurred in the gp gene segment coding for the SCA. An additional N-glycosylation
      site was created by one of the mutations. The adapted virus showed higher density
      of gp on the viral envelope, improved infectivity, much greater stability, higher
      burst size, and decreased induction of cellular interferon. The specificity for
      cells expressing the Her2/neu receptor was unchanged. These studies demonstrate
      that serial passage can be used to rapidly evolve a VSV genome encoding an
      improved chimeric glycoprotein.

PMID- 16912310
TI  - Endoplasmic reticulum stress and neurodegeneration in rats neonatally infected
      with borna disease virus.
AB  - Borna disease virus infection of neonatal rats results in a characteristic
      behavioral syndrome and apoptosis of subsets of neurons in the hippocampus and
      cerebellum (neonatal Borna disease [NBD]). The cellular mechanisms leading to
      neurodevelopmental damage in NBD have not been fully elucidated. Insights into
      this model may have general implications for understanding the pathogenesis of
      virus-associated neurodevelopmental damage. Here we report the presence of
      endoplasmic reticulum (ER) stress markers and activation of the unfolded protein
      response in the NBD hippocampus and cerebellum. Specific findings included
      enhanced PERK-mediated phosphorylation of eif2alpha and concomitant regulation of
      ATF4 translation; IRE1-mediated splicing of XBP1 mRNA; and cleavage of the ATF6
      protein in NBD rat brains. We found evidence for regional and cell type-specific
      divergence in the expression of ER stress-induced proapoptotic and quality
      control signals. Our results demonstrate that ER stress induction in death
      susceptible Purkinje neurons in NBD is associated with the expression of the
      proapoptotic molecule CHOP in the absence of compensatory expression of the ER
      quality control molecules Bip and protein disulfide isomerase. In contrast, ER
      stress in death-resistant astrocytes is associated with complementary expression
      of CHOP and ER quality control signals. These results implicate an imbalance
      between ER stress-mediated apoptosis and survival signaling as a critical
      determinant of neural cell fate in NBD.

PMID- 16912311
TI  - Role of Bim in regulating CD8+ T-cell responses during chronic viral infection.
AB  - Apoptosis is critical for the development and maintenance of the immune system.
      The proapoptotic Bcl-2 family member Bim is important for normal immune system
      homeostasis. Although previous experiments have shown that Bim is critical for
      the apoptosis of antigen-specific CD8(+) T cells during acute viral infection,
      the role of Bim during chronic viral infection is unclear. Using lymphocytic
      choriomeningitis virus clone 13 infection of mice, we demonstrate a role for Bim
      in CD8(+) T-cell apoptosis during chronic viral infection. Enumeration of antigen
      specific CD8(+) T cells by major histocompatibility complex class I tetramer
      staining revealed that CD8(+) D(b)NP396-404(+) T cells, which undergo extensive
      deletion in wild-type mice, exhibited almost no decrease in Bim mutant mice. This
      contrasts with CD8(+) D(b)GP33-41(+) and CD8(+) D(b)GP276-286(+) T cells that
      underwent similar decreases in numbers in both Bim mutant and wild-type mice.
      Increased numbers of CD8(+) D(b)NP396-404(+) T cells in Bim mutant mice were due
      to lack of apoptosis and could not be explained by altered proliferation,
      differential homing to tissues, or increased help from CD4(+) T cells. When viral
      titers were examined, high levels were initially observed in both groups, but in
      Bim mutant mice, clearance from the spleen and sera was slightly accelerated.
      These experiments demonstrate the critical role of Bim during chronic viral
      infection to down-regulate CD8(+) T-cell responses and have implications for
      designing strategies for optimizing immunotherapies during situations where
      antigen persists, such as chronic infection, autoimmune syndromes, and cancer.

PMID- 16912312
TI  - Highly conserved regions within the spike proteins of human coronaviruses 229E
      and NL63 determine recognition of their respective cellular receptors.
AB  - We have recently demonstrated that the severe acute respiratory syndrome
      coronavirus (SARS-CoV) receptor angiotensin converting enzyme 2 (ACE2) also
      mediates cellular entry of the newly discovered human coronavirus (hCoV) NL63.
      Here, we show that expression of DC-SIGN augments NL63 spike (S)-protein-driven
      infection of susceptible cells, while only expression of ACE2 but not DC-SIGN is
      sufficient for entry into nonpermissive cells, indicating that ACE2 fulfills the
      criteria of a bona fide hCoV-NL63 receptor. As for SARS-CoV, murine ACE2 is used
      less efficiently by NL63-S for entry than human ACE2. In contrast, several amino
      acid exchanges in human ACE2 which diminish SARS-S-driven entry do not interfere
      with NL63-S-mediated infection, suggesting that SARS-S and NL63-S might engage
      human ACE2 differentially. Moreover, we observed that NL63-S-driven entry was
      less dependent on a low-pH environment and activity of endosomal proteases
      compared to infection mediated by SARS-S, further suggesting differences in hCoV
      NL63 and SARS-CoV cellular entry. NL63-S does not exhibit significant homology to
      SARS-S but is highly related to the S-protein of hCoV-229E, which enters target
      cells by engaging CD13. Employing mutagenic analyses, we found that the N
      terminal unique domain in NL63-S, which is absent in 229E-S, does not confer
      binding to ACE2. In contrast, the highly homologous C-terminal parts of the NL63
      S1 and 229E-S1 subunits in conjunction with distinct amino acids in the central
      regions of these proteins confer recognition of ACE2 and CD13, respectively.
      Therefore, despite the high homology of these sequences, they likely form
      sufficiently distinct surfaces, thus determining receptor specificity.

PMID- 16912313
TI  - Rational design of genetically stable, live-attenuated poliovirus vaccines of all
      three serotypes: relevance to poliomyelitis eradication.
AB  - The global eradication of poliomyelitis caused by wild-type virus is likely to be
      completed within the next few years, despite immense logistic and political
      difficulties, and may ultimately be followed by the cessation of vaccination.
      However, the existing live-attenuated vaccines have the potential to revert to
      virulence, causing occasional disease, and viruses can be shed by
      immunocompromised individuals for prolonged periods of time. Moreover, several
      outbreaks of poliomyelitis have been shown to be caused by viruses derived from
      the Sabin vaccine strains. The appearance of such strains depends on the
      prevailing circumstances but poses a severe obstacle to strategies for stopping
      vaccination. Vaccine strains that are incapable of reversion at a measurable rate
      would provide a possible solution. Here, we describe the constructions of strains
      of type 3 poliovirus that are stabilized by the introduction of four mutations in
      the 5' noncoding region compared to the present vaccine. The strains are
      genetically and phenotypically stable under conditions where the present vaccine
      loses the attenuating mutation in the 5' noncoding region completely. Type 1 and
      type 2 strains in which the entire 5' noncoding regions of Sabin 1 and Sabin 2
      were replaced exactly with that of one of the type 3 strains were also
      constructed. The genetic stability of 5' noncoding regions of these viruses
      matched that of the type 3 strains, but significant phenotypic reversion
      occurred, illustrating the potential limitations of a rational approach to the
      genetic stabilization of live RNA virus vaccines.

PMID- 16912314
TI  - Characterization of a UL49-null mutant: VP22 of herpes simplex virus type 1
      facilitates viral spread in cultured cells and the mouse cornea.
AB  - Herpes simplex virus type 1 (HSV-1) virions, like those of all herpesviruses,
      contain a proteinaceous layer termed the tegument that lies between the
      nucleocapsid and viral envelope. The HSV-1 tegument is composed of at least 20
      different viral proteins of various stoichiometries. VP22, the product of the
      U(L)49 gene, is one of the most abundant tegument proteins and is conserved among
      the alphaherpesviruses. Although a number of interesting biological properties
      have been attributed to VP22, its role in HSV-1 infection is not well understood.
      In the present study we have generated both a U(L)49-null virus and its genetic
      repair and characterized their growth in both cultured cells and the mouse
      cornea. While single-step growth analyses indicated that VP22 is dispensable for
      virus replication at high multiplicities of infection (MOIs), analyses of plaque
      morphology and intra- and extracellular multistep growth identified a role for
      VP22 in viral spread during HSV-1 infection at low MOIs. Specifically, VP22 was
      not required for either virion infectivity or cell-cell spread but was required
      for accumulation of extracellular virus to wild-type levels. We found that the
      absence of VP22 also affected virion composition. Intracellular virions generated
      by the U(L)49-null virus contained reduced amounts of ICP0 and glycoproteins E
      and D compared to those generated by the wild-type and U(L)49-repaired viruses.
      In addition, viral spread in the mouse cornea was significantly reduced upon
      infection with the U(L)49-null virus compared to infection with the wild-type and
      U(L)49-repaired viruses, identifying a role for VP22 in viral spread in vivo as
      well as in vitro.

PMID- 16912315
TI  - Poxviral regulation of the host NF-kappaB response: the vaccinia virus M2L
      protein inhibits induction of NF-kappaB activation via an ERK2 pathway in virus
      infected human embryonic kidney cells.
AB  - Exposure of eukaryotic cells to viruses will activate the host NF-kappaB
      transcription factor, resulting in proinflammatory and immune protein production.
      Vaccinia virus (VV), the prototypic orthopoxvirus, expresses products that
      inhibit this antiviral event. To identify novel mechanisms responsible for this
      effect, we made use of a VV deletion mutant (MVA) that stimulates NF-kappaBeta
      activation in infected 293T cells. In this virus-host system, the extents of NF
      kappaBeta-regulated gene expression and nuclear translocation were reduced in the
      presence of either PD 98059 or U0126, two compounds capable of blocking ERK1 and
      ERK2 phosphorylation. A similar repression was also observed in cells that
      contained a dominant, nonactive form of ERK2 but not in cells where ERK1
      phosphorylation was inhibited via overexpression of a dominant-negative mutant
      MEK1 protein. Presumably, proteins expressed from a wild-type VV that block ERK2
      activity would also inhibit MVA-induced NF-kappaB activation. Indeed, the
      expression of one such open reading frame, M2L, supported this prediction. First,
      ectopic M2L expression hampered ERK2 phosphorylation induced by exposure to
      phorbol myristate acetate. Second, viral M2L expression via infection of cells
      with a recombinant MVA construct that stably expressed M2L decreased the
      phosphorylation of ERK2 compared to that in cells infected with the parental MVA
      strain. Finally, the recombinant M2L-expressing virus restored the "wild-type" NF
      kappaB-inhibitory phenotype, as indicated by decreased NF-kappaB migration to
      infected cell nuclei and interference in transcription. Thus, in 293T cells, VV
      apparently utilizes its M2L protein to interfere with a step(s) that would
      otherwise enable ERK2 phosphorylation and the consequential activation of an NF
      kappaBeta response.

PMID- 16912316
TI  - Rolling-circle replication of an animal circovirus genome in a theta-replicating
      bacterial plasmid in Escherichia coli.
AB  - A bacterial plasmid containing 1.75 copies of double-stranded porcine circovirus
      (PCV) DNA in tandem (0.8 copy of PCV type 1 [PCV1], 0.95 copy of PCV2) with two
      origins of DNA replication (Ori) yielded three different DNA species when
      transformed into Escherichia coli: the input construct, a unit-length chimeric
      PCV1(Rep)/PCV2(Cap) genome with a composite Ori but lacking the plasmid vector,
      and a molecule consisting of the remaining 0.75 copy PCV1(Cap)/PCV2(Rep) genome
      with a different composite Ori together with the bacterial plasmid. Replication
      of the input construct was presumably via the theta replication mechanism
      utilizing the ColE(1) Ori, while characteristics of the other two DNA species,
      including a requirement of two PCV Oris and the virus-encoded replication
      initiator Rep protein, suggest they were generated via the rolling-circle copy
      release mechanism. Interestingly, the PCV-encoded Rep' protein essential for PCV
      DNA replication in mammalian cells was not required in bacteria. The fact that
      the Rep' protein function(s) can be compensated by the bacterial replication
      machinery to support the PCV DNA replication process echoes previous suggestions
      that circular single-stranded DNA animal circoviruses, plant geminiviruses, and
      nanoviruses may have evolved from prokaryotic episomal replicons.

PMID- 16912317
TI  - Identification of conserved residues in the E2 envelope glycoprotein of the
      hepatitis C virus that are critical for CD81 binding.
AB  - Hepatitis C virus (HCV) cell entry involves interaction between the viral
      envelope glycoprotein E2 and the cell surface receptor CD81. Knowledge of
      conserved E2 determinants important for successful binding will facilitate
      development of entry inhibitors designed to block this interaction. Previous
      studies have assigned the CD81 binding function to a number of discontinuous
      regions of E2. To better define specific residues involved in receptor binding, a
      panel of mutants of HCV envelope proteins was generated, where conserved residues
      within putative CD81 binding regions were sequentially mutated to alanine. Mutant
      proteins were tested for binding to a panel of monoclonal antibodies and CD81 and
      for their ability to form noncovalent heterodimers and confer infectivity in the
      retroviral pseudoparticle (HCVpp) assay. Detection by conformation-sensitive
      monoclonal antibodies indicated that the mutant proteins were correctly folded.
      Mutant proteins fell into three groups: those that bound CD81 and conferred HCVpp
      infectivity, those that abrogated both CD81 binding and HCVpp infectivity, and a
      final group containing mutants that were able to bind CD81 but were noninfectious
      in the HCVpp assay. Specific amino acids conserved across all genotypes that were
      critical for CD81 binding were W420, Y527, W529, G530, and D535. These data
      significantly increase our understanding of the CD81 receptor-E2 binding process.

PMID- 16912318
TI  - Phenotype-based identification of host genes required for replication of African
      swine fever virus.
AB  - African swine fever virus (ASFV) produces a fatal acute hemorrhagic fever in
      domesticated pigs that potentially is a worldwide economic threat. Using an
      expressed sequence tag (EST) library-based antisense method of random gene
      inactivation and a phenotypic screen for limitation of ASFV replication in
      cultured human cells, we identified six host genes whose cellular functions are
      required by ASFV. These included three loci, BAT3 (HLA-B-associated transcript
      3), C1qTNF (C1q and tumor necrosis factor-related protein 6), and TOM40
      (translocase of outer mitochondrial membrane 40), for which antisense expression
      from a tetracycline-regulated promoter resulted in reversible inhibition of ASFV
      production by >99%. The effects of antisense transcription of the BAT3 EST and
      also of expression in the sense orientation of this EST, which encodes amino acid
      residues 450 to 518 of the mature BAT3 protein, were investigated more
      extensively. Sense expression of the BAT3 peptide, which appears to reversibly
      interfere with BAT3 function by a dominant negative mechanism, resulted in
      decreased synthesis of viral DNA and proteins early after ASFV infection, altered
      transcription of apoptosis-related genes as determined by cDNA microarray
      analysis, and increased cellular sensitivity to staurosporine-induced apoptosis.
      Antisense transcription of BAT3 reduced ASFV production without affecting
      abundance of the virus macromolecules we assayed. Our results, which demonstrate
      the utility of EST-based functional screens for the detection of host genes
      exploited by pathogenic viruses, reveal a novel collection of cellular genes
      previously not known to be required for ASFV infection.

PMID- 16912319
TI  - The E6 protein of the cutaneous human papillomavirus type 8 can stimulate the
      viral early and late promoters by distinct mechanisms.
AB  - The expression of the proteins encoded by human papillomaviruses (HPVs) is
      tightly linked to the differentiation program of the infected keratinocytes. The
      late promoter, expressing the structural proteins, becomes activated in the
      differentiated keratinocytes, while the early promoter is also active in the
      basal layers. We have shown previously that the viral transcriptional regulator
      E2 and the cellular coactivator p300 cooperate in activation of gene expression
      of HPV8, which infects the skin and is associated with epidermodysplasia
      verruciformis. Here we demonstrate that this activation is further stimulated
      after overexpression of the E6 oncoprotein of HPV8 (8E6). RNase protection
      experiments revealed that 8E6 efficiently cooperates with 8E2 and p300 in
      activation of the late promoter. In addition, the early promoter, which did not
      respond to 8E2 and/or p300, was stimulated more than fourfold by 8E6. Our data
      suggest that both promoters are activated via distinct mechanisms, since the
      activation of the early promoter was achieved by the N-terminal moiety of 8E6; in
      contrast, its C-terminal half was sufficient for late promoter activation. This
      was markedly reduced by the deletion of amino acids 132 to 136 of 8E6, which also
      abolished the binding to p300, indicating that a direct interaction between 8E6
      and p300 is involved. Moreover, a 45-amino-acid segment within the C/H3 region of
      p300 is required for 8E6 to stimulate the coactivator function of p300. Our
      results demonstrate for the first time that an E6 oncoprotein of HPV directly
      contributes to the regulation of HPV gene expression.

PMID- 16912320
TI  - Molecularly cloned SHIV-1157ipd3N4: a highly replication- competent, mucosally
      transmissible R5 simian-human immunodeficiency virus encoding HIV clade C Env.
AB  - Human immunodeficiency virus type 1 (HIV-1) clade C causes >50% of all HIV
      infections worldwide, and an estimated 90% of all transmissions occur mucosally
      with R5 strains. A pathogenic R5 simian-human immunodeficiency virus (SHIV)
      encoding HIV clade C env is highly desirable to evaluate candidate AIDS vaccines
      in nonhuman primates. To this end, we generated SHIV-1157i, a molecular clone
      from a Zambian infant isolate that carries HIV clade C env. SHIV-1157i was
      adapted by serial passage in five monkeys, three of which developed peripheral
      CD4(+) T-cell depletion. After the first inoculated monkey developed AIDS at week
      137 postinoculation, transfer of its infected blood to a naive animal induced
      memory T-cell depletion and thrombocytopenia within 3 months in the recipient. In
      parallel, genomic DNA from the blood donor was amplified to generate the late
      proviral clone SHIV-1157ipd3. To increase the replicative capacity of SHIV
      1157ipd3, an extra NF-kappaB binding site was engineered into its 3' long
      terminal repeat, giving rise to SHIV-1157ipd3N4. This virus was exclusively R5
      tropic and replicated more potently in rhesus peripheral blood mononuclear cells
      than SHIV-1157ipd3 in the presence of tumor necrosis factor alpha. Rhesus
      macaques of Indian and Chinese origin were next inoculated intrarectally with
      SHIV-1157ipd3N4; this virus replicated vigorously in both sets of monkeys. We
      conclude that SHIV-1157ipd3N4 is a highly replication-competent, mucosally
      transmissible R5 SHIV that represents a valuable tool to test candidate AIDS
      vaccines targeting HIV-1 clade C Env.

PMID- 16912321
TI  - Murine polyomavirus requires the endoplasmic reticulum protein Derlin-2 to
      initiate infection.
AB  - The pathways by which viruses enter cells are diverse, but in all cases,
      infection necessitates the transfer of the viral genome across a cellular
      membrane. Polyomavirus (Py) particles, after binding to glycolipid and
      glycoprotein receptors at the cell surface, are delivered to the lumen of the
      endoplasmic reticulum (ER). The nature and extent of virus disassembly in the ER,
      how the viral genome is transported to the cytosol and subsequently to the
      nucleus, and whether any cellular proteins are involved are not known. Here, we
      identify an ER-resident protein, Derlin-2, a factor implicated in the removal of
      misfolded proteins from the ER for cytosolic degradation, as a component of the
      machinery required for mouse Py to establish an infection. Inhibition of Derlin-2
      function by expression of either a dominant-negative form of Derlin-2 or a short
      hairpin RNA that reduces Derlin-2 levels blocks Py infection by 50 to 75%. The
      block imposed by Derlin-2 inhibition occurs after the virus reaches the ER and
      can be bypassed by the introduction of Py DNA into the cytosol. These findings
      suggest a mode of Py entry that involves cytosolic access via the quality control
      machinery in the ER.

PMID- 16912323
TI  - Interaction between vaccinia virus extracellular virus envelope A33 and B5
      glycoproteins.
AB  - The extracellular form of vaccinia virus acquires its outer envelope by wrapping
      with cytoplasmic membranes that contain at least seven virus-encoded proteins, of
      which four are glycoproteins. We searched for interactions between the vaccinia
      virus A33 glycoprotein and proteins A34, A36, B5, F12, and F13. First, when myc
      epitope-tagged A33 was expressed in combination with other envelope proteins, A33
      colocalized with B5 and A36, suggesting that direct A33-B5 and A33-A36
      interactions occur in the absence of infection. A recombinant vaccinia virus
      (vA33Rmyc) was constructed by introduction of the myc-tagged A33 version (A33myc)
      into A33-deficient vaccinia virus. A33myc partially restored plaque formation and
      colocalized with enveloped virions in infected cells. Coimmunoprecipitation
      experiments with extracts of vA33Rmyc-infected cells confirmed the existence of a
      physical association of A33 with A36 and B5. Of these, the A33-B5 interaction is
      a novel finding, whereas the interaction between A33 and A36 has been previously
      characterized. A collection of vaccinia viruses expressing mutated versions of
      the B5 protein was used to investigate the domain(s) of B5 required for
      interaction with A33. Both the cytoplasmic domain and most of the extracellular
      domain, but not the transmembrane domain, of the B5 protein were dispensable for
      binding to A33. Mutations in the extracellular portions of B5 and A33 that
      enhance extracellular virus release did not affect the interaction between the
      two. In contrast, substituting the B5 transmembrane domain with that of the
      vesicular stomatitis virus G glycoprotein prevented the association with A33.
      Immunofluorescence experiments on virus mutants indicated that B5 is required for
      efficient targeting of A33 into enveloped virions. These results point to the
      transmembrane domain of B5 as the major determinant of the A33-B5 interaction and
      demonstrate that protein-protein interactions are crucial in determining the
      composition of the virus envelope.

PMID- 16912322
TI  - Antibody responses elicited in macaques immunized with human immunodeficiency
      virus type 1 (HIV-1) SF162-derived gp140 envelope immunogens: comparison with
      those elicited during homologous simian/human immunodeficiency virus SHIVSF162P4
      and heterologous HIV-1 infection.
AB  - The antibody responses elicited in rhesus macaques immunized with soluble human
      immunodeficiency virus (HIV) Env gp140 proteins derived from the R5-tropic HIV-1
      SF162 virus were analyzed and compared to the broadly reactive neutralizing
      antibody responses elicited during chronic infection of a macaque with a
      simian/human immunodeficiency virus (SHIV) expressing the HIV-1 SF162 Env,
      SHIV(SF162P4), and humans infected with heterologous HIV-1 isolates. Four gp140
      immunogens were evaluated: SF162gp140, DeltaV2gp140 (lacking the crown of the V2
      loop), DeltaV3gp140 (lacking the crown of the V3 loop), and DeltaV2DeltaV3gp140
      (lacking both the V2 and V3 loop crowns). SF162gp140 and DeltaV2gp140 have been
      previously evaluated by our group in a pilot study, but here, a more
      comprehensive analysis of their immunogenic properties was performed. All four
      gp140 immunogens elicited stronger anti-gp120 than anti-gp41 antibodies and
      potent homologous neutralizing antibodies (NAbs) that primarily targeted the
      first hypervariable region (V1 loop) of gp120, although SF162gp140 also elicited
      anti-V3 NAbs. Heterologous NAbs were elicited by SF162gp140 and DeltaV2gp140 but
      were weak in potency and narrow in specificity. No heterologous NAbs were
      elicited by DeltaV3gp140 or DeltaV2DeltaV3gp140. In contrast, the SHIV(SF162P4)
      infected macaque and HIV-infected humans generated similar titers of anti-gp120
      and anti-gp41 antibodies and NAbs of significant breadth against primary HIV-1
      isolates, which did not target the V1 loop. The difference in V1 loop
      immunogenicity between soluble gp140 and virion-associated gp160 Env proteins
      derived from SF162 may be the basis for the observed difference in the breadth of
      neutralization in sera from the immunized and infected animals studied here.

PMID- 16912324
TI  - Marek's disease virus encodes MicroRNAs that map to meq and the latency
      associated transcript.
AB  - MicroRNAs (miRNAs) are a class of small (approximately 22-nucleotide) regulatory
      molecules that block translation or induce degradation of target mRNAs. These
      have been identified in a wide range of organisms, including viruses. In
      particular, the oncogenic gammaherpesviruses Kaposi's sarcoma herpesvirus and
      Epstein-Barr virus encode miRNAs that could potentially regulate either viral or
      host genes. To determine if Marek's disease virus (MDV), an oncogenic
      alphaherpesvirus of chickens, encodes miRNAs, we isolated small RNAs from MDV
      infected chicken embryo fibroblasts (CEF) and used the 454 Life Sciences
      sequencing technology to obtain the sequences of 13,679 candidate host and viral
      small RNAs. Eight miRNAs were found, five of which flank the meq oncogene and
      three that map to the latency-associated transcript (LAT) region of the genome.
      The meq gene is unique to pathogenic serotypes of MDV and is transcriptionally
      active during latency and transformation, and the LAT region of the MDV genome is
      antisense to the immediate-early gene ICP4. Secondary structure analysis
      predicted that the regions flanking the miRNAs could form hairpin precursors.
      Northern blot analysis confirmed expression of all miRNAs in MDV-infected CEF,
      MDV-induced tumors, and MDV lymphoblastoid cell lines. We propose that the MDV
      miRNAs function to enable MDV pathogenesis and contribute to MDV-induced
      transformation of chicken T cells.

PMID- 16912325
TI  - Importance of neuraminidase active-site residues to the neuraminidase inhibitor
      resistance of influenza viruses.
AB  - Neuraminidase inhibitors (NAIs) are antivirals designed to target conserved
      residues at the neuraminidase (NA) enzyme active site in influenza A and B
      viruses. The conserved residues that interact with NAIs are under selective
      pressure, but only a few have been linked to resistance. In the A/Wuhan/359/95
      (H3N2) recombinant virus background, we characterized seven charged, conserved NA
      residues (R118, R371, E227, R152, R224, E276, and D151) that directly interact
      with the NAIs but have not been reported to confer resistance to NAIs. These NA
      residues were replaced with amino acids that possess side chains having similar
      properties to maintain their original charge. The NA mutations we introduced
      significantly decreased NA activity compared to that of the A/Wuhan/359/95
      recombinant wild-type and R292K (an NA mutation frequently reported to confer
      resistance) viruses, which were analyzed for comparison. However, the recombinant
      viruses differed in replication efficiency when we serially passaged them in
      vitro; the growth of the R118K and E227D viruses was most impaired. The R224K,
      E276D, and R371K mutations conferred resistance to both zanamivir and
      oseltamivir, while the D151E mutation reduced susceptibility to oseltamivir only
      (approximately 10-fold) and the R152K mutation did not alter susceptibility to
      either drug. Because the R224K mutation was genetically unstable and the
      emergence of the R371K mutation in the N2 subtype is statistically unlikely, our
      results suggest that only the E276D mutation is likely to emerge under selective
      pressure. The results of our study may help to optimize the design of NAIs.

PMID- 16912326
TI  - Mobility of human immunodeficiency virus type 1 Pr55Gag in living cells.
AB  - Human immunodeficiency virus type 1 (HIV-1) assembly requires the converging of
      thousands of structural proteins on cellular membranes to form a tightly packed
      immature virion. The Gag polyprotein contains all of the determinants important
      for viral assembly and must move around in the cell in order to form particles.
      This work has focused on Gag mobility in order to provide more insights into the
      dynamics of particle assembly. Key to these studies was the use of several
      fluorescently labeled Gag derivatives. We used fluorescence recovery after
      photobleaching as well as photoactivation to determine Gag mobility. Upon
      expression, Gag can be localized diffusely in the cytoplasm, associated with the
      plasma membrane, or in virus-like particles (VLPs). Here we show that Gag VLPs
      are primarily localized in the plasma membrane and do not colocalize with CD63.
      We have shown using full-length Gag as well as truncation mutants fused to green
      fluorescent protein that Gag is highly mobile in live cells when it is not
      assembled into VLPs. Results also showed that this mobility is highly dependent
      upon cholesterol. When cholesterol is depleted from cells expressing Gag,
      mobility is significantly decreased. Once cholesterol was replenished, Gag
      mobility returned to wild-type levels. Taken together, results from these
      mobility studies suggest that Gag is highly mobile and that as the assembly
      process proceeds, mobility decreases. These studies also suggest that Gag
      assembly must occur in cholesterol-rich domains in the plasma membrane.

PMID- 16912328
TI  - Integration site choice of a feline immunodeficiency virus vector.
AB  - We mapped 226 unique integration sites in human hepatoma cells following gene
      transfer with a feline immunodeficiency virus (FIV)-based lentivirus vector. FIV
      integrated across the entire length of the transcriptional units. Microarray data
      indicated that FIV integration favored actively transcribed genes. Approximately
      21% of FIV integrations within transcriptional units occurred in genes regulated
      by the LEDGF/p75 transcriptional coactivator. DNA in regions of FIV insertion
      sites exhibited a "bendable" structure and a pattern of duplex destabilization
      favoring strand separation. FIV integration preferences are more similar to those
      of primate lentiviruses and distinct from those of Moloney murine leukemia virus,
      avian sarcoma leukosis virus, and foamy virus.

PMID- 16912327
TI  - Role of the envelope genetic context in the development of enfuvirtide resistance
      in human immunodeficiency virus type 1-infected patients.
AB  - Acquired human immunodeficiency virus type 1(HIV-1) resistance to the fusion
      inhibitor enfuvirtide (ENF) is primarily associated with mutations within the
      highly conserved first heptad repeat (HR1) region of gp41. Viral env sequences,
      however, are remarkably variable, and the envelope genetic background could have
      an important impact on optimal expression of HR1 mutations. We have examined the
      genetic evolution of env sequences, ENF susceptibility, and Env replicative
      capacity in patients failing ENF treatment. Sequential plasma-derived virus
      populations, obtained from six patients initiating ENF treatment as part of a
      salvage therapy, were studied using a recombinant phenotypic assay evaluating the
      entire gp120 and the gp41 ectodomains. Regardless of major differences in the
      baseline ENF susceptibilities, viral populations with similar phenotypic ENF
      resistance (50% inhibitory concentration, >3,000 ng/ml) were selected under
      treatment in four of six patients. As expected, in all patients ENF-resistant
      viruses harbored one or more HR1 mutations (positions 36, 38, and 43).
      Interestingly, in five patients the emergence of resistance mutations was not
      associated with reduced Env replicative capacity. Phylogenetic analysis of env
      sequences in sequential samples from two patients showed that the HR1 mutations
      had emerged in the context of env quasi-species that were different from those
      prevalent at baseline. Thus, the envelope genetic context appears to play a
      critical role in the selection of HR1 mutations and the expression of ENF
      resistance, thereby conditioning the evolution of HIV-1 under fusion inhibitor
      selective pressure.

PMID- 16912329
TI  - Intra- and intersubtype alternative Pak2-activating structural motifs of human
      immunodeficiency virus type 1 Nef.
AB  - The design of antiviral strategies against human immunodeficiency virus type 1
      (HIV-1) has been largely derived from studies of subtype B viruses, although they
      constitute only 12% of infections worldwide. At 50% of all HIV-1 infections
      worldwide, subtype C viruses are the most predominant. Here, we present evidence
      that subtype C Nefs display functional Pak2-activating motifs that differ from
      those found in subtype B and E Nefs. The identification of multiple Pak2
      activating structural motifs that singly affect one Nef activity revealed a
      functional plasticity that has implications for future drug and vaccine design
      aimed at HIV-1 Nef and its effects on the deregulation of the immune system.

PMID- 16912330
TI  - Functional entry of baculovirus into insect and mammalian cells is dependent on
      clathrin-mediated endocytosis.
AB  - Entry of the budded virus form of baculoviruses into insect and mammalian cells
      is generally thought to occur through a low-pH-dependent endocytosis pathway,
      possibly through clathrin-coated pits. This insight is primarily based on
      (immuno)electron microscopy studies but requires biochemical support to exclude
      the use of other pathways. Here, we demonstrate using various inhibitors that
      functional entry of baculoviruses into insect and mammalian cells is primarily
      dependent on clathrin-mediated endocytosis. Our results further suggest that
      caveolae are somehow involved in baculovirus entry in mammalian cells. A caveolar
      endocytosis inhibitor, genistein, enhances baculovirus transduction in these
      cells considerably.

PMID- 16912333
TI  - Tracing the decline of OMT in patient care.

PMID- 16912331
TI  - Crimean-Congo hemorrhagic fever virus genomics and global diversity.
AB  - Crimean-Congo hemorrhagic fever (CCHF) is a severe illness with high case
      fatality that occurs in Africa, Europe, the Middle East, and Asia. The complete
      genomes of 13 geographically and temporally diverse virus strains were
      determined, and CCHF viruses were found to be highly variable with 20 and 8%, 31
      and 27%, and 22 and 10% nucleotide and deduced amino acid differences detected
      among virus S (nucleocapsid), M (glycoprotein), and L (polymerase) genome
      segments, respectively. Distinct geographic lineages exist, but with multiple
      exceptions indicative of long-distance virus movement. Discrepancies among the
      virus S, M, and L phylogenetic tree topologies document multiple RNA segment
      reassortment events. An analysis of individual segment datasets suggests genetic
      recombination also occurs. For an arthropod-borne virus, the genomic plasticity
      of CCHF virus is surprisingly high.

PMID- 16912334
TI  - OMT: evidence, research, and practice.

PMID- 16912337
TI  - Treatment and prevention practices in postmenopausal women after bone mineral
      density screening at a community-based osteoporosis project.
AB  - OBJECTIVE: To determine the use of treatment and prevention practices in
      postmenopausal women who have received the results of an osteoporosis screening.
      METHODS: Telephone survey to follow-up with women who underwent dual-energy x-ray
      absorptiometry scanning at a community-wide osteoporosis screening project.
      Participants categorized by their scan results as having normal bone mineral
      density or low bone mineral density were asked about their osteoporosis treatment
      and prevention practices since receiving their scan results. RESULTS: Two hundred
      nineteen women were interviewed. Calcium supplement use increased significantly
      in both groups (P=.002). There was no significant difference in the number of
      women using alendronate sodium, calcitonin, and selective estrogen receptor
      modulators before and after screening. Both groups reported increases in exercise
      levels and dairy intake, but the difference was not statistically significant.
      CONCLUSIONS: Our results indicate that the use of over-the-counter calcium
      supplements increases after osteoporosis screening. However, the use of
      treatments that require a physician prescription does not increase after
      screening regardless of the patient's bone mineral density status.

PMID- 16912336
TI  - Venous thromboembolism: application and effectiveness of the American College of
      Chest Physicians 2001 guidelines for prophylaxis.
AB  - CONTEXT: Guidelines on the use of prophylaxis in venous thromboembolism (VTE) are
      poorly implemented in clinical practice. OBJECTIVE: To evaluate the extent to
      which the American College of Chest Physicians (ACCP) 2001 guidelines on VTE
      prophylaxis are adhered to in clinical practice by determining whether patients
      admitted to a medical center with an objective diagnosis of VTE had received
      adequate prophylaxis. METHODS: The medical records of medical and surgery
      patients with an objective diagnosis of VTE were reviewed. Patients were
      classified as having either preventable or nonpreventable VTE according to
      indication for prophylaxis, VTE risk, and adequacy of prophylaxis if
      administered. Adequacy was determined by adherence to the ACCP 2001 guidelines.
      RESULTS: Of 44 patients, 17 (38.6%) had not received adequate prophylaxis and
      were classified as having potentially preventable VTE. Venous thromboembolism
      developed in the remaining 27 (61.4%) patients despite adequate prophylaxis. In
      general, adequate prophylaxis rates were lower among surgery patients compared
      with medical patients. Four (80%) of the very-high-risk surgery patients received
      inadequate prophylaxis. The most common VTE risk factor in both categories was
      immobility. CONCLUSIONS: Adherence to the ACCP guidelines is suboptimal, with a
      substantial proportion of patients with VTE receiving inadequate prophylaxis. The
      additional finding that the incidence of VTE is high despite adequate prophylaxis
      indicates that the guidelines may need to be reevaluated.

PMID- 16912338
TI  - How misconceptions among elderly patients regarding survival outcomes of
      inpatient cardiopulmonary resuscitation affect do-not-resuscitate orders.
AB  - CONTEXT: On hospital admission, many elderly patients make the decision to enact
      a do-not-resuscitate (DNR) order. However, few studies have evaluated the beliefs
      of elderly patients regarding the likelihood of surviving cardiopulmonary
      resuscitation (CPR) if it should become necessary during their hospitalization.
      OBJECTIVES: To quantify elderly patients' beliefs about their chances of survival
      to discharge following CPR; to ascertain the sources of information that may lead
      to these beliefs; and to determine how these beliefs affect decisions regarding
      DNR orders. METHODS: An oral standardized survey was administered to 100 patients
      aged 70 years or older. Patients were randomly selected from the emergency
      department, internal medicine clinic, and general medical wards at one urban
      medical center. RESULTS: Most respondents (81%) believed that their chance of
      surviving inpatient CPR and leaving the hospital was 50% or better, and 23% of
      those respondents believed that their chance was 90% or better. Forty-four
      percent of patients reported having a standing DNR order. Most patients reported
      obtaining healthcare information from television, physicians, or both.
      CONCLUSION: Elderly patients often hold erroneous beliefs regarding the outcomes
      of inpatient CPR. A significant number of our participants had standing DNR
      orders despite demonstrating extremely optimistic beliefs about CPR. Educating
      patients and their families about these poor outcomes would allow them to make
      more informed decisions regarding end-of-life issues.

PMID- 16912339
TI  - "Hang Up Your Pocketbook" -- an easy intervention for the granny syndrome:
      grandparents as a risk factor in unintentional pediatric exposures to
      pharmaceuticals.
AB  - CONTEXT: Although the circumstances are not well studied, grandparents'
      medications account for 10% to 20% of unintentional pediatric intoxications in
      the United States. OBJECTIVES: To characterize circumstances leading to and
      outcomes from pediatric pharmaceutical exposures. To identify preventable risk
      factors associated with this pattern of injury, referred to as the "granny
      syndrome." DESIGN, SETTING, AND PARTICIPANTS: Retrospective review of records of
      telephone calls made to a certified regional poison control center in the United
      States. Records were analyzed for all calls concerning children aged 6 years or
      younger who were exposed to grandparents' medication(s). For statistical
      analysis, regression and chi(2) analysis as well as Fisher exact tests were used.
      The sample size provided 80% power to detect a 10% difference at the 5% level of
      significance. Statistical significance was set at P< or =.05. MAIN OUTCOMES
      MEASURED: Use of child-resistant containers (CRCs), the location of
      pharmaceuticals prior to pediatric ingestion, and drug classes involved (eg,
      analgesics, cardiovascular drugs). RESULTS: Of the 200 incidents analyzed, 90
      (45%) cases involved CRCs, and 110 (55%) involved containers that were not child
      resistant. For these incidents, the average age of the child was 18.8 months; the
      grandparent was aged on average 58.7 years. Most medications had been placed on
      tables or countertops (91 [46%]), low shelves (57 [29%]), or in pocketbooks (34
      [17%]). The type of container in which the pharmacologic agent was stored (CRC vs
      non-CRC) was not statistically significant (P>.1). Ease of access to medication,
      regardless of the type of container used, was the only statistically significant
      outcome (P<.001). In the present study, accidental pediatric exposures most
      frequently involved cardiovascular (90 [45%]), analgesic (84 [42%]), and
      psychotropic (32 [16%]) medications. CONCLUSION: Pediatric exposure to
      pharmaceutical agents is a preventable cause of injury. Physicians have an
      important opportunity to assist in preventing pediatric pharmaceutical exposures
      by instructing parents and grandparents on how to better limit children's access
      to medications as an essential component to enhance child safety.

PMID- 16912340
TI  - Neuropsychiatric symptoms and medical illness in patients with dementia: an
      exploratory study.
AB  - OBJECTIVE: To determine the association between neuropsychiatric symptoms and the
      presence of medical illness among outpatients with mild dementia. METHOD: The
      Neuropsychiatric Inventory (NPI) was used to assess neuropsychiatric symptoms,
      and the Cumulative Illness Rating Scale (CIRS) was used to evaluate physical
      impairment, in 44 outpatients diagnosed as having dementia (Alzheimer disease,
      n=22; vascular dementia, n=13; mixed dementia, n=9). The tests used were standard
      parts of a memory assessment program at a college of osteopathic medicine.
      Pearson product moment correlations were used to assess any associations between
      NPI and CIRS scores. RESULTS: Significant associations were identified between
      several NPI-assessed symptoms and degree of medical illness as measured by the
      CIRS. Neurobehavioral problems were significantly correlated (P<.05) with illness
      in the following body organ systems: gastrointestinal (lower), genitourinary,
      neurologic, ophthalmologic/otolaryngologic, psychiatric, and respiratory.
      CONCLUSION: The authors' preliminary data underscore the importance of primary
      care physicians assessing patients with dementia for comorbidity of psychiatric
      illnesses when conducting medical examinations.

PMID- 16912341
TI  - Periodontal disease and control of diabetes mellitus.
AB  - Data from the Centers for Disease Control and Prevention indicate that more than
      20 million people (approximately 7% of the population) in the United States have
      diabetes mellitus. Physicians often fail to examine the mouths and teeth of their
      patients, even though the condition of the mouth and teeth have clinical
      relevance for the treatment of patients with diabetes mellitus. The authors
      examine the current state of knowledge regarding periodontal disease and the
      effect of periodontal disease on worsening of glycemic control. They review
      several studies investigating how the management of periodontal disease affects
      the ability of patients to control symptoms of diabetes mellitus. The authors
      conclude with several recommendations for the treatment of patients with
      periodontal disease to improve glycemic control.

PMID- 16912342
TI  - "Circle turns round" to "allopathic osteopathy".

PMID- 16912343
TI  - Sexually activated or transmitted? Questions about HPV.

PMID- 16912344
TI  - Addressing substance abuse in medical school curricula.

PMID- 16912345
TI  - Cochrane Library's summary of review on manipulative treatment misleading, cheats
      readers.

PMID- 16912346
TI  - Worlds of Western medicine and Chinese medicine learning from each other.

PMID- 16912347
TI  - Violations of the 80-duty-hours work standard to be investigated.

PMID- 16912348
TI  - Proof-of-concept learning: acrylic templates as empiric evidence.

PMID- 16912349
TI  - Using lithium.

PMID- 16912350
TI  - Use of lithium in the treatment of thyrotoxicosis.
AB  - OBJECTIVES: To evaluate the efficacy and safety of lithium in the treatment of
      thyrotoxicosis, and to study the dose and serum levels at which therapeutic
      response occurs. DESIGN: Retrospective study. SETTING: Thyroid clinic of a
      regional hospital in Hong Kong. PATIENTS: Thirteen patients with thyrotoxicosis
      pending therapy with radioiodine or surgery, in whom thionamides were contra
      indicated due to adverse reactions or failure of treatment. MAIN OUTCOME
      MEASURES: Free thyroxine levels, time to euthyroidism, and side-effects of
      lithium. RESULTS: A satisfactory response, defined as a fall by 40% or more in
      free thyroxine levels and clinical improvement, was achieved in eight patients
      within 1 to 2 weeks of lithium therapy. In four others, response occurred in 3 to
      5 weeks. Response was slow and inadequate in one patient due to 'escape'. The
      median dosage of lithium was 750 mg daily, with a range of 500 to 1500 mg daily.
      The median serum lithium level was 0.63 mmol/L. Lithium toxicity was observed in
      one patient. CONCLUSIONS: A relatively low dose of lithium offers a safe and
      effective alternative means of controlling thyrotoxicosis in patients who cannot
      tolerate or do not respond to thionamides.

PMID- 16912351
TI  - Seizure-related injury in an adult tertiary epilepsy clinic.
AB  - OBJECTIVE: To assess the frequency, characteristics, and risk of injury during
      seizure attacks. DESIGN: Questionnaire survey. SETTING: Epilepsy out-patient
      clinic of the National Hospital for Neurology and Neurosurgery, Institute of
      Neurology, London. PATIENTS: One hundred consecutive epileptic patients and their
      caretakers or relatives, who attended the hospital between 1 May and 30 June
      2000. MAIN OUTCOME MEASURES: Details of epilepsy including the age of onset,
      causes, types, and number of seizures during the previous 12 months; injuries
      incurred as a result of seizures; and treatment required. RESULTS: The mean age
      of the 100 patients (38 male, 62 female) was 39 years (range, 16-78 years).
      Generalised tonic-clonic seizures occurred in 51% of patients and complex partial
      seizures in 40%. Hippocampal sclerosis was found in 12% of patients. Twenty-seven
      patients reported 222 seizure-related injuries. The total number of seizures per
      year was 4459 (mean, 45), of which 1094 (mean, 11) were with a fall (24.5%). Soft
      tissue injury was the most common (61%), followed by burns (17%), head injury
      (14%), orthopaedic injury (5%), and injuries in water (3%). The most common site
      of soft-tissue injury and burns were to the face: 49% and 38% respectively. Burns
      occurred during cooking in 78% of cases. Two patients had skull fractures.
      Orthopaedic injuries usually occurred at home (73%). In cases of seizures in
      water, five of six occurred while swimming. Injury occurred once in every 20
      seizures, every 11 generalised tonic-clonic seizures, and every five seizures
      with a fall. The significant risk factors for injury were generalised tonic
      clonic seizures, high frequency of seizures, and seizures with a fall.
      CONCLUSION: Soft-tissue injury was the most common seizure-related injury. Injury
      occurred once in every 20 seizures. The risk factors were generalised tonic
      clonic seizures, high frequency of seizures, and seizures with a fall.

PMID- 16912352
TI  - Intestinal tuberculosis in a regional hospital in Hong Kong: a 10-year
      experience.
AB  - OBJECTIVE: To study the clinical and pathological characteristics of patients
      with intestinal tuberculosis. DESIGN: Retrospective study. SETTING: United
      Christian Hospital, Hong Kong. PATIENTS: Patients with intestinal tuberculosis
      diagnosed between January 1995 and December 2004 inclusive. RESULTS: The median
      age of the 13 male and 9 female patients was 53 years (range, 12-81 years).
      Nineteen (86%) had a definitive diagnosis of intestinal tuberculosis confirmed by
      the presence of caseating granulomas and/or acid-fast bacilli in histological
      specimens. In three (14%) the diagnosis was based on histology revealing non
      caseating granulomas and a positive response to anti-tuberculous treatment.
      Common symptoms included abdominal pain (82%), diarrhoea (55%), weight loss
      (55%), and fever (45%). Three (14%) of the patients were complicated by
      intestinal obstruction, and another two (9%) had intestinal perforation. Four
      (18%) had concomitant active pulmonary tuberculosis. The most frequently involved
      site was the ileocaecal region, which was affected in 19 (86%) patients. Other
      sites included the jejunum, ascending and sigmoid colon. The diagnosis of
      intestinal tuberculosis was facilitated by examination of colonoscopic biopsy
      specimens (11 patients), and by examination of resected surgical specimens in the
      remainder. Two patients died from terminal malignancy. The remainder completed
      anti-tuberculous therapy and responded satisfactorily. CONCLUSIONS: The diagnosis
      of intestinal tuberculosis is difficult due to the lack of specific signs or
      symptoms. Colonoscopy with ileoscopy are useful tools in the search for colonic
      and terminal ileal tuberculosis. Surgical exploration is reserved for equivocal
      cases and for those who present as emergencies.

PMID- 16912353
TI  - Cutaneous tuberculosis in Hong Kong: an update.
AB  - OBJECTIVE: To provide an update on cutaneous tuberculosis in Hong Kong. DESIGN:
      Retrospective study. SETTING: Social Hygiene Service (Dermatology Division), the
      largest dermatological referral centre in Hong Kong. PATIENTS: Patients presented
      with cutaneous tuberculosis between 1993 and 2002 inclusive. Case notes,
      histology reports, and microbiological reports were reviewed with particular
      reference to the epidemiology, duration of illness, history of contact with
      tuberculosis, culture results, and response to treatment. RESULTS: There were 147
      patients with cutaneous tuberculosis; among these a few had true cutaneous
      tuberculosis (n = 16) and the remainder were tuberculids (n = 131). In all they
      accounted for 0.04% of new dermatology cases diagnosed. Cases of cutaneous
      tuberculosis were distributed as follows: lupus vulgaris (n = 6, 4%),
      tuberculosis verrucosa cutis (n = 6, 4%), tuberculosis of the skin unclassified
      (n = 2, 1%), and orificial tuberculosis (n = 2, 1%). Culture and polymerase chain
      reaction was positive in less than half of the latter cases. All responded well
      to anti-tuberculosis therapy. Erythema induratum was the most common form (n =
      127, 86%), but papulonecrotic tuberculids (n = 4, 3%) were uncommon. Erythema
      induratum affected the lower limb in all patients, with a female predominance,
      and responded to isoniazid monotherapy, multidrug anti-tuberculosis therapy, or
      doxycycline. CONCLUSION: Lupus vulgaris and tuberculosis verrucosa cutis remain
      the commonest forms of true cutaneous tuberculosis, and erythema induratum is the
      most common tuberculid. Culture and polymerase chain reaction are positive in a
      small proportion of patients.

PMID- 16912354
TI  - Subcutaneous extralesional triamcinolone acetonide injection versus conservative
      management in the treatment of chalazion.
AB  - OBJECTIVE: To compare the efficacy of subcutaneous extralesional triamcinolone
      acetonide injection versus conservative treatment for chalazion. DESIGN:
      Randomised controlled trial. SETTING: Eye clinics of two regional hospitals in
      Hong Kong. PATIENTS: Patients over 18 years old presenting with primary chalazion
      were randomised into two groups. In group 1, 12 patients were treated with lid
      hygiene, warm compresses, and chloramphenicol 1% ointment 4 times a day. In group
      2, 16 patients were treated with 0.3 mL triamcinolone acetonide (10 mg/mL)
      injection to the subcutaneous tissue extralesionally via the percutaneous route.
      Exclusion criteria were: acutely infected chalazion with preseptal cellulitis,
      recurrent chalazion, small chalazion (< or =2 mm), and prior treatment to
      chalazion. MAIN OUTCOME MEASURES: Size of chalazion, recurrence of chalazion,
      intra-ocular pressure, and complications from treatment, including skin
      pigmentary change or atrophy and pyogenic granuloma. RESULTS: There was a
      clinically and statistically significant difference between the success rates in
      group 1 (58.3%) and group 2 (93.8%). In group 1, the mean prior duration of
      chalazion before treatment was significantly shorter in success cases than in
      failed cases. One patient with multiple chalazia in group 2 developed
      hypopigmentary skin changes at one treatment site. CONCLUSION: Subcutaneous
      extralesional triamcinolone acetonide injection was more effective than
      conservative treatment for chalazion.

PMID- 16912355
TI  - Nissen fundoplication and gastrostomy in severely neurologically impaired
      children with gastroesophageal reflux.
AB  - OBJECTIVES: To study the effect of Nissen fundoplication and gastrostomy in
      severely neurologically impaired children. DESIGN: Prospective observational
      study. SETTING: Developmental Disabilities Unit of a regional medical centre in
      Hong Kong. PATIENTS: Children with severe neurological impairment and
      gastroesophageal reflux who were institutionalised between 1999 and 2004
      inclusive. MAIN OUTCOME MEASURES: Incidence of vomiting, gastro-intestinal
      bleeding, and pneumonia in the baseline year and consecutive years following
      surgery; 24-hour oesophageal pH monitoring; recurrence rate (determined by 24
      hour oesophageal monitoring); body weight; complications of surgery; and
      mortality. RESULTS: Twenty children, with a mean age at surgery of 8.5 (standard
      deviation, 3.5) years, were recruited. Nissen fundoplication was performed in
      nine children and 11 children underwent laparoscopic fundoplication. Children
      were monitored for 1.3 to 5.7 years (median, 3.5 years) after surgery. The
      incidence of vomiting and gastro-intestinal bleeding was significantly decreased
      following surgery (P < 0.001 and P = 0.001, respectively; Friedman's test). There
      was no difference between the preoperative and postoperative incidence of
      pneumonia (P = 0.973, Friedman's test). The median reflux index was reduced from
      5.7% to 0.15% after surgery but six (30%) patients had recurrent gastroesophageal
      reflux. The mean body weight was 17.4 kg (standard deviation, 4.7 kg) at baseline
      and 22.8 kg (standard deviation, 4.4 kg) at the end of follow-up (P < 0.05,
      Student's t test). One patient had mild dumping syndrome soon after
      fundoplication. One patient had one episode of intestinal obstruction. Four
      patients died 1.9 to 5.0 years following surgery due to respiratory disease.
      CONCLUSION: Our results indicate that in severely neurologically impaired
      children with gastroesophageal reflux, vomiting, gastro-intestinal bleeding, and
      reflux indices based on 24-hour oesophageal pH monitoring were significantly
      reduced following fundoplication and gastrostomy. The incidence of pneumonia was
      unchanged. The recurrence rate of reflux was 30% and mortality rate was 20%.

PMID- 16912356
TI  - Risk factors for injury to married women from domestic violence in Hong Kong.
AB  - OBJECTIVE: To examine risk factors for injury to married women from domestic
      violence in Hong Kong. DESIGN: Case control study. SETTING: Regional public
      hospital, Hong Kong. PATIENTS: All married women aged 18 to 60 years who attended
      an accident and emergency department for treatment of a domestic violence injury
      from January 2004 to June 2005. MAIN OUTCOME MEASURES: Social and health
      characteristics of abused women and their husbands. RESULTS: A total of 293 cases
      were compared to 313 controls. Eight predictive variables were found to be
      significant by univariate analysis: woman who is a new immigrant (P = 0.003),
      woman with no job (P = 0.019), husband with low educational level (P < 0.001),
      presence of extramarital affairs (P < 0.001), husband's unemployment (P < 0.001),
      husband's alcohol abuse (P < 0.001), husband's illicit drug abuse (P = 0.032),
      husband's mental illness (P < 0.001). Five factors were found to be significant
      in a logistic regression analysis: husband with a low educational level (nil to
      primary) [adjusted odds ratio = 2.78; 95% confidence interval, 1.149-6.727],
      husband unemployed (adjusted odds ratio = 9.031; 95% confidence interval, 5.163
      15.796), presence of extramarital affairs (adjusted odds ratio = 5.218; 95%
      confidence interval, 2.899-9.395), husband's alcohol abuse (adjusted odds ratio =
      6.089; 95% confidence interval, 3.460-10.716), husband's mental illness (adjusted
      odds ratio = 9.443; 95% confidence interval, 2.351-37.926). CONCLUSIONS: Several
      significant risk factors have been identified for injury incurred during domestic
      violence to married women in Hong Kong. It provides information useful for
      developing local preventive strategies.

PMID- 16912357
TI  - Ocular toxicity of hydroxychloroquine.
AB  - OBJECTIVES: To review the types, incidence, pathogenesis, risk factors, and
      clinical characteristics of hydroxychloroquine ocular toxicity and current views
      about its screening and management. DATA SOURCES: Literature search of Medline up
      to May 2005. STUDY SELECTION: Key words for the literature search were
      'hydroxychloroquine', 'chloroquine', 'ocular', 'toxicity', 'retinopathy', and
      'screening'. DATA EXTRACTION: Original articles and review papers were examined.
      DATA SYNTHESIS: Hydroxychloroquine ocular toxicity includes keratopathy, ciliary
      body involvement, lens opacities, and retinopathy. Retinopathy is the major
      concern: others are more common but benign. The incidence of true
      hydroxychloroquine retinopathy is exceedingly low; less than 50 cases have been
      reported. Although its pathogenesis is unclear, risk factors include: daily
      dosage of hydroxychloroquine, cumulative dosage, duration of treatment,
      coexisting renal or liver disease, patient age, and concomitant retinal disease.
      Patients usually complain of difficulty in reading, decreased vision, missing
      central vision, glare, blurred vision, light flashes, and metamorphopsia. They
      can also be asymptomatic. Most patients have a bull's eye fundoscopic appearance.
      All patients have field defects including paracentral, pericentral, central, and
      peripheral field loss. Colour vision is usually undisturbed in early retinopathy,
      but is impaired in the advanced stage. Most patients have visual loss. Some
      patients with advanced retinopathy may experience deteriorating visual acuity
      even after cessation of treatment. There is no consensus on the definition of
      retinopathy, most-effective ophthalmological assessment, or frequency of
      screening. Regular screening may be necessary to detect reversible
      premaculopathy. Cessation of the drug is the only effective management of the
      toxicity. CONCLUSION: Consensus with regard to various important aspects of
      hydroxychloroquine ocular toxicity is limited, especially the definition of true
      hydroxychloroquine retinopathy, the most effective ophthalmological assessment,
      and frequency of screening. Decisions to stop medication must be made in
      conjunction with the rheumatologist or physician managing the patient. Management
      of hydroxychloroquine retinopathy remains a clinical challenge.

PMID- 16912358
TI  - Computed tomography-guided percutaneous radiofrequency ablation of osteoid
      osteoma: local experience.
AB  - Osteoid osteoma is a slow-growing tumour with limited growth potential. In the
      past, treatment comprised open surgery with en-bloc resection or curettage of the
      tumour. In recent years, various minimally invasive percutaneous treatments have
      gained popularity. We report on six patients who underwent computed tomography
      guided percutaneous radiofrequency ablations of osteoid osteomas between January
      2000 and December 2003 in a regional hospital in Hong Kong. Technical success was
      achieved in all procedures, with a mean follow-up of 40 months (range, 18-65
      months). Five of the six patients achieved complete pain relief after the
      procedure and remained pain-free on subsequent follow-up. One patient with
      persistent symptoms after the first ablation was successfully treated with a
      second ablation. The mean in-hospital stay was 2.4 days. Progress in radiological
      healing was observed in all patients. There was one complication of skin burn
      over the needle entry site. Our experience shows that percutaneous computed
      tomography-guided radiofrequency ablation is a minimally invasive and cost
      effective treatment for osteoid osteoma.

PMID- 16912359
TI  - Transvenous embolisation of a carotid-trigeminal cavernous fistula.
AB  - A carotid cavernous fistula is an abnormal communication between the internal
      carotid artery and the cavernous sinus. Rarely, this communication is associated
      with a persistent primitive trigeminal artery, with or without a trigeminal
      artery aneurysm. We report a case of spontaneous carotid-trigeminal cavernous
      fistula in which the persistent trigeminal artery was shown only on vertebral
      artery injection. The absence of an associated trigeminal artery aneurysm allowed
      a transvenous approach for endovascular treatment with coils and complete
      obliteration of the cavernous fistula.

PMID- 16912360
TI  - Tuberculosis intestinal perforation during anti-tuberculosis treatment.
AB  - Intestinal perforation is an uncommon but potentially fatal complication of
      intestinal tuberculosis. We report on a 63-year-old HIV-negative man who
      developed terminal ileal perforation approximately 3.5 months following
      initiation of anti-tuberculous treatment for pulmonary tuberculosis and a
      concomitant tuberculous perianal abscess. Clinical and radiological improvements
      were initially evident following commencement of anti-tuberculous treatment, and
      the paradoxical response phenomenon was suspected. The patient subsequently
      underwent surgical resection of the affected bowel segment with primary
      anastomosis, and made an uneventful recovery. Anti-tuberculous medication was
      continued for another 12 months, and after a further 12 months there was no
      evidence of recurrent tuberculosis. This case illustrates that tuberculous
      intestinal perforation can develop during chemotherapy for tuberculosis. Prompt
      diagnosis and appropriate surgical treatment are essential to avoid morbidity and
      mortality.

PMID- 16912361
TI  - Minimal change disease following exposure to mercury-containing skin lightening
      cream.
AB  - A 34-year-old woman developed nephrotic syndrome after using a skin lightening
      cream that contained an extremely high level of mercury. Blood and urine mercury
      levels were elevated and a renal biopsy revealed minimal change disease.
      Membranous nephropathy was excluded using immunofluorescence and electron
      microscopy. Her proteinuria remitted 9 months after she stopped using the
      cosmetic cream. This is the first reported case in the English literature of
      proven minimal change disease secondary to mercury exposure. It is important that
      mercury poisoning due to cosmetic cream is considered in the differential
      diagnoses for any woman who presents with nephrotic syndrome.

PMID- 16912362
TI  - Oncogenic osteomalacia associated with an occult phosphaturic mesenchymal tumour:
      clinico-radiologico-pathological correlation and ultrastructural studies.
AB  - A middle-aged man presented with bone pain at multiple sites due to tumour
      induced osteomalacia. The underlying occult phosphaturic mesenchymal tumour was
      identified by octreotide scan 5 years after presentation and confirmed by
      computed tomography. Tumour resection resulted in normalisation of blood
      chemistry and bone densitometry. Clinico-radiologico-pathological correlation and
      ultrastructural studies of the tumour threw light on the pathogenesis and
      pathophysiology of this rare disease.

PMID- 16912363
TI  - Screening for intimate partner violence in emergency departments.

PMID- 16912364
TI  - Evidence-based public health practices: challenges for health needs assessments
      in disasters.

PMID- 16912365
TI  - A prospective case-control study of ankle fracture in postmenopausal women.

PMID- 16912366
TI  - Non-contact infrared thermal imagers may still be useful for mass fever
      screening.

PMID- 16912367
TI  - Tetrahedral irradiation protocol for microbeam radiation therapy.
AB  - Optimizing microbeam radiation therapy requires that the patient be repositioned
      between exposures. Optional movements of a patient-gantry are described that
      would enable a lesion to be cross-fired pseudo-orthogonally in two, three or four
      exposures to a fixed, horizontally propagated array of vertical, parallel
      microplanar beams, with minimal tilting of the patient-gantry.

PMID- 16912368
TI  - Measurement for the MLC leaf velocity profile by considering the leaf leakage
      using a radiographic film.
AB  - A method to measure the velocity profile of a multi-leaf collimator (MLC) leaf
      along its travel range using a radiographic film is reported by considering the
      intra-leaf leakage. A specific dynamic MLC field with leaves travelling from the
      field edge to the isocentre line was designed. The field was used to expose a
      radiographic film, which was then scanned, and the dose profile along the
      horizontal leaf axis was measured. The velocity at a sampling point on the film
      can be calculated by considering the horizontal distance between the sampling
      point and the isocentre line, dose at the sampling point, dose rate of the linear
      accelerator, the total leaf travel time from the field edge to isocentre line and
      the pre-measured dose rate of leaf leakage. With the leaf velocities and velocity
      profiles for all MLC leaves measured routinely, a comprehensive and simple QA for
      the MLC can be set up to test the consistency of the leaf velocity performance
      which is essential to the IMRT delivery using a sliding window technique.

PMID- 16912369
TI  - Downscatter correction and choice of collimator in 123I imaging.
AB  - (123)I imaging is increasingly used in nuclear medicine but downscatter from high
      (>300 keV) energy emissions degrades the image and introduces variation in
      sensitivity with depth when imaging with a low energy collimator. A dual
      windowing technique using a matched window immediately above the principle window
      to correct for the effects of downscatter is described. The technique is shown to
      correct for the variation in sensitivity with depth and to reduce outlying
      scatter. Quantitative imaging of (123)I using a low energy collimator should
      always employ downscatter correction.

PMID- 16912370
TI  - The use of the Henyey-Greenstein phase function in Monte Carlo simulations in
      biomedical optics.
AB  - Monte Carlo (MC) simulations are often at the heart of the testing procedure in
      biomedical optics. One of the critical points in MC simulations is to define the
      new photon direction after each scattering event. One of the most popular
      solutions is to use the Henyey-Greenstein phase function or some linear
      combinations of it. In this note, we demonstrate that randomly generating the
      angle defining the new direction of a photon after a collision, by means of the
      Henyey-Greenstein phase function, is not equivalent to generating the cosine of
      this angle, as is classically done. In practice, it is demonstrated that for a
      nearly isotropic medium (asymmetry parameter g approximately 0) this discrepancy
      is not large, however for an anisotropic medium as is typically found in vivo
      (e.g. g = 0.98) the two methods give completely different results.

PMID- 16912371
TI  - The three-photon yield from e+ annihilation in various fluids.
AB  - Positronium in the triplet state decays by the emission of three photons and it
      has been proposed that their simultaneous detection can be used for medical
      imaging. The three-photon yield has been observed to be enhanced in low O(2)
      levels in some fluids but has never been measured in biologically relevant
      liquids. In this study, the delayed three-photon decay yield, at both high and
      low O(2) levels, has been extracted by fitting the time dependence of the two
      photon yield to a set of coupled differential equations. The differential
      equations, in a simple yet seemingly satisfactory fashion, account for the e(+)
      capture to form positronium, its decay and the interconversion of the two spin
      configurations. Our results indicate that the delayed three-photon fraction is
      0.25% in water (or blood-like) samples and exhibits no (or exceedingly small)
      dependence on the dissolved oxygen content. If one assumes that the direct
      component contributes a fraction expected by annihilation on free electrons
      (1/372), then the total three-photon fraction is 0.52% in the samples of
      biological relevance.

PMID- 16912372
TI  - FDTD calculation of whole-body average SAR in adult and child models for
      frequencies from 30 MHz to 3 GHz.
AB  - Due to the difficulty of the specific absorption rate (SAR) measurement in an
      actual human body for electromagnetic radio-frequency (RF) exposure, in various
      compliance assessment procedures the incident electric field or power density is
      being used as a reference level, which should never yield a larger whole-body
      average SAR than the basic safety limit. The relationship between the reference
      level and the whole-body average SAR, however, was established mainly based on
      numerical calculations for highly simplified human modelling dozens of years ago.
      Its validity is being questioned by the latest calculation results. In verifying
      the validity of the reference level with respect to the basic SAR limit for RF
      exposure, it is essential to have a high accuracy of human modelling and
      numerical code. In this study, we made a detailed error analysis in the whole
      body average SAR calculation for the finite-difference time-domain (FDTD) method
      in conjunction with the perfectly matched layer (PML) absorbing boundaries. We
      derived a basic rule for the PML employment based on a dielectric sphere and the
      Mie theory solution. We then attempted to clarify to what extent the whole-body
      average SAR may reach using an anatomically based Japanese adult model and a
      scaled child model. The results show that the whole-body average SAR under the
      ICNIRP reference level exceeds the basic safety limit nearly 30% for the child
      model both in the resonance frequency and 2 GHz band.

PMID- 16912373
TI  - Experimental determination of particle range and dose distribution in thick
      targets through fragmentation reactions of stable heavy ions.
AB  - In radiation therapy with highly energetic heavy ions, the conformal irradiation
      of a tumour can be achieved by using their advantageous features such as the good
      dose localization and the high relative biological effectiveness around their
      mean range. For effective utilization of such properties, it is necessary to
      evaluate the range of incident ions and the deposited dose distribution in a
      patient's body. Several methods have been proposed to derive such physical
      quantities; one of them uses positron emitters generated through projectile
      fragmentation reactions of incident ions with target nuclei. We have proposed the
      application of the maximum likelihood estimation (MLE) method to a detected
      annihilation gamma-ray distribution for determination of the range of incident
      ions in a target and we have demonstrated the effectiveness of the method with
      computer simulations. In this paper, a water, a polyethylene and a polymethyl
      methacrylate target were each irradiated with stable (12)C, (14)N, (16)O and
      (20)Ne beams. Except for a few combinations of incident beams and targets, the
      MLE method could determine the range of incident ions R(MLE) with a difference
      between R(MLE) and the experimental range of less than 2.0 mm under the
      circumstance that the measurement of annihilation gamma rays was started just
      after the irradiation of 61.4 s and lasted for 500 s. In the process of
      evaluating the range of incident ions with the MLE method, we must calculate many
      physical quantities such as the fluence and the energy of both primary ions and
      fragments as a function of depth in a target. Consequently, by using them we can
      obtain the dose distribution. Thus, when the mean range of incident ions is
      determined with the MLE method, the annihilation gamma-ray distribution and the
      deposited dose distribution can be derived simultaneously. The derived dose
      distributions in water for the mono-energetic heavy-ion beams of four species
      were compared with those measured with an ionization chamber. The good agreement
      between the derived and the measured distributions implies that the deposited
      dose distribution in a target can be estimated from the detected annihilation
      gamma-ray distribution with a positron camera.

PMID- 16912374
TI  - MRI-based measurements of respiratory motion variability and assessment of
      imaging strategies for radiotherapy planning.
AB  - Respiratory organ motion has a significant impact on the planning and delivery of
      radiotherapy (RT) treatment for lung cancer. Currently widespread techniques,
      such as 4D-computed tomography (4DCT), cannot be used to measure variability of
      this motion from one cycle to the next. In this paper, we describe the use of
      fast magnetic resonance imaging (MRI) techniques to investigate the intra- and
      inter-cycle reproducibility of respiratory motion and also to estimate the level
      of errors that may be introduced into treatment delivery by using various breath
      hold imaging strategies during lung RT planning. A reference model of respiratory
      motion is formed to enable comparison of different breathing cycles at any
      arbitrary position in the respiratory cycle. This is constructed by using free
      breathing images from the inhale phase of a single breathing cycle, then co
      registering the images, and thereby tracking landmarks. This reference model is
      then compared to alternative models constructed from images acquired during the
      exhale phase of the same cycle and the inhale phase of a subsequent cycle, to
      assess intra- and inter-cycle variability ('hysteresis' and 'reproducibility') of
      organ motion. The reference model is also compared to a series of models formed
      from breath-hold data at exhale and inhale. Evaluation of these models is carried
      out on data from ten healthy volunteers and five lung cancer patients. Free
      breathing models show good levels of intra- and inter-cycle reproducibility
      across the tidal breathing range. Mean intra-cycle errors in the position of
      organ surface landmarks of 1.5(1.4)-3.5(3.3) mm for volunteers and 2.8(1.8)
      5.2(5.2) mm for patients. Equivalent measures of inter-cycle variability across
      this range are 1.7(1.0)-3.9(3.3) mm for volunteers and 2.8(1.8)-3.3(2.2) mm for
      patients. As expected, models based on breath-hold sequences do not represent
      normal tidal motion as well as those based on free-breathing data, with mean
      errors of 4.4(2.2)-7.7(3.9) mm for volunteers and 10.1(6.1)-12.5(6.3) mm for
      patients. Errors are generally larger still when using a single breath-hold image
      at either exhale or inhale to represent the lung. This indicates that account
      should be taken of intra- and inter-cycle respiratory motion variability and that
      breath-hold-based methods of obtaining data for RT planning may potentially
      introduce large errors. This approach to analysis of motion and variability has
      potential to inform decisions about treatment margins and optimize RT planning.

PMID- 16912375
TI  - An NMR relaxometry and gravimetric study of gelatin-free aqueous polyacrylamide
      dosimeters.
AB  - In conformal radiation therapy, a high dose of radiation is given to a target
      volume to increase the probability of cure, and care is taken to minimize the
      dose to surrounding healthy tissue. The techniques used to achieve this are very
      complicated and the precise verification of the resulting three-dimensional (3D)
      dose distribution is required. Polyacrylamide gelatin (PAG) dosimeters with
      magnetic resonance imaging and optical computed tomography scanning provide the
      required 3D dosimetry with high spatial resolution. Many basic studies have
      characterized these chemical dosimeters that polymerize under irradiation.
      However, the investigation of the fundamental properties of the radiation-induced
      polymerization in PAG dosimeters is complicated by the presence of the background
      gelatin matrix. In this work, a gelatin-free model system for the study of the
      basic radiation-induced polymerization in PAG dosimeters has been developed.
      Experiments were performed on gelatin-free dosimeters, named aqueous
      polyacrylamide (APA) dosimeters, containing equal amounts of acrylamide and N,N'
      methylene-bisacrylamide. The APA dosimeters were prepared with four different
      total monomer concentrations (2, 4, 6 and 8% by weight). Nuclear magnetic
      resonance (NMR) spin-spin and spin-lattice proton relaxation measurements at 20
      MHz, and gravimetric analyses performed on all four dosimeters, show a continuous
      degree of polymerization over the dose range of 0-25 Gy. The developed NMR model
      explains the relationship observed between the relaxation data and the amount of
      crosslinked polymer formed at each dose. This model can be extended with gelatin
      relaxation data to provide a fundamental understanding of radiation-induced
      polymerization in the conventional PAG dosimeters.

PMID- 16912376
TI  - An intercomparison of 11 amorphous silicon EPIDs of the same type: implications
      for portal dosimetry.
AB  - The use of electronic portal imaging devices (EPIDs) for portal dosimetry
      requires knowledge of their dosimetric properties. The pixel value response of
      amorphous silicon EPIDs of type Elekta iViewGT is known to be nonlinear with
      dose. However, it is not clear whether these nonlinearities vary with time and
      from one detector to another, respectively. In the present study, the dose
      response characteristics of 11 iViewGT EPIDs were investigated with respect to
      dose rate, total dose and field size. It was found that each detector needs to be
      individually calibrated, not only in terms of absolute sensitivity but also with
      respect to its relative response variations with exposure parameters. Doubling
      the dose rate typically increased the EPID signal between 1.4% and 2.8%. Changing
      the number of monitor units from 30 to 500 was accompanied by an increase in
      detector sensitivity between 1.7% and 2.8%. The EPID scatter factors were always
      within +/-1%. It was observed that the dose-response behaviour was not stable
      with respect to time. Particularly within the first weeks of operation, detector
      ageing caused variations in both absolute sensitivity and relative response
      curves. It is recommended to establish a quality assurance programme if the
      amorphous silicon EPIDs are intended to be used for clinical portal dosimetry.

PMID- 16912377
TI  - Generating positive contrast from off-resonant spins with steady-state free
      precession magnetic resonance imaging: theory and proof-of-principle experiments.
AB  - It is well known that magnetic susceptibility variations lead to signal voids in
      MRI. However, recent work has shown that positive-contrast imaging of
      susceptibility-induced field variations can provide signal enhancements rather
      than signal losses. In this paper, we propose a new method for generating
      positive contrast from off-resonant spins with steady-state free precession
      (SSFP) magnetic resonance imaging. Based on theory and experiments, we
      demonstrate that positive-contrast images can be acquired in the presence of
      susceptibility-shift media with low flip angle excitations that are determined by
      the spin relaxation time constants of the imaging medium. Compared to other
      techniques, this technique is substantially faster and has low specific
      absorption rates, permitting high-field imaging. In addition to acquiring
      positive-contrast images, we also show that it is possible to suppress the
      imaging medium to desired levels; thereby allowing for simultaneous registration
      of the background details surrounding the susceptibility-shift media. Among
      practical applications, we anticipate that the proposed technique can potentially
      facilitate high field magnetic-resonance-based molecular imaging.

PMID- 16912378
TI  - Optimization algorithms and weighting factors for analysis of dynamic PET
      studies.
AB  - Positron emission tomography (PET) pharmacokinetic analysis involves fitting of
      measured PET data to a PET pharmacokinetic model. The fitted parameters may,
      however, suffer from bias or be unrealistic, especially in the case of noisy
      data. There are many optimization algorithms, each having different
      characteristics. The purpose of the present study was to evaluate (1) the
      performance of different optimization algorithms and (2) the effects of using
      incorrect weighting factors during optimization in terms of both accuracy and
      reproducibility of fitted PET pharmacokinetic parameters. In this study, the
      performance of commonly used optimization algorithms (i.e. interior-reflective
      Newton methods) and a simulated annealing (SA) method was evaluated. This SA
      algorithm, known as basin hopping, was modified for the present application. In
      addition, optimization was performed using various weighting factors. Algorithms
      and effects of using incorrect weighting factors were studied using both
      simulated and clinical time-activity curves (TACs). Input data, taken from
      [(15)O]H(2)O, [(11)C]flumazenil and [(11)C](R)-PK11195 studies, were used to
      simulate time-activity curves at various variance levels (0-15% COV). Clinical
      evaluation was based on studies with the same three tracers. SA was able to
      produce accurate results without the need for selecting appropriate starting
      values for (kinetic) parameters, in contrast to the interior-reflective Newton
      method. The latter gave biased results unless it was modified to allow for a
      range of starting values for the different parameters. For patient studies, where
      large variability is expected, both SA and the extended Newton method provided
      accurate results. Simulations and clinical assessment showed similar results for
      the evaluation of different weighting models in that small to intermediate
      mismatches between data variance and weighting factors did not significantly
      affect the outcome of the fits. Large errors were observed only when the mismatch
      between weighting model and data variance was large. It is concluded that
      selection of specific optimization algorithms and weighting factors can have a
      large effect on the accuracy and precision of PET pharmacokinetic analysis. Apart
      from carefully selecting appropriate algorithms and variance models, further
      improvement in accuracy might be obtained by using noise reducing strategies,
      such as wavelet filtering, provided that these methods do not introduce
      significant bias.

PMID- 16912379
TI  - Evaluation of the minimum iodine concentration for contrast-enhanced subtraction
      mammography.
AB  - Early manifestation of breast cancer is often very subtle and is displayed in a
      complex and variable pattern of normal anatomy that may obscure the disease. The
      use of dual-energy techniques, that can remove the structural noise, and contrast
      media, that enhance the region surrounding the tumour, could help us to improve
      the detectability of the lesions. The aim of this work is to investigate the use
      of an iodine-based contrast medium in mammography with two different double
      exposure techniques: K-edge subtraction mammography and temporal subtraction
      mammography. Both techniques have been investigated by using an ideal source,
      like monochromatic beams produced at a synchrotron radiation facility and a
      clinical digital mammography system. A dedicated three-component phantom
      containing cavities filled with different iodine concentrations has been
      developed and used for measurements. For each technique, information about the
      minimum iodine concentration, which provides a significant enhancement of the
      detectability of the pathology by minimizing the risk due to high dose and high
      concentration of contrast medium, has been obtained. In particular, for cavities
      of 5 and 8 mm in diameter filled with iodine solutions, the minimum concentration
      needed to obtain a contrast-to-noise ratio of 5 with a mean glandular dose of 2
      mGy has been calculated. The minimum concentrations estimated with monochromatic
      beams and K-edge subtraction mammography are 0.9 mg ml(-1) and 1.34 mg ml(-1) for
      the biggest and smallest details, respectively, while for temporal subtraction
      mammography they are 0.84 mg ml(-1) and 1.31 mg ml(-1). With the conventional
      clinical system the minimum concentrations for the K-edge subtraction mammography
      are 4.13 mg ml(-1) (8 mm diameter) and 5.75 mg ml(-1) (5 mm diameter), while for
      the temporal subtraction mammography they are 1.01 mg ml(-1) (8 mm diameter) and
      1.57 mg ml(-1) (5 mm diameter).

PMID- 16912380
TI  - A new method of body habitus correction for total body potassium measurements.
AB  - This paper describes an accurate and time-efficient method for the determination
      of total body potassium via a combination of measurements in the Birmingham whole
      body counter and the use of the Monte Carlo n-particle (MCNP) simulation code. In
      developing this method, MCNP has also been used to derive values for some
      components of the total measurement uncertainty which are difficult to quantify
      experimentally. A method is proposed for MCNP-assessed body habitus corrections
      based on a simple generic anthropomorphic model, scaled for individual height and
      weight. The use of this model increases patient comfort by reducing the need for
      comprehensive anthropomorphic measurements. The analysis shows that the total
      uncertainty in potassium weight determination by this whole body counting
      methodology for water-filled phantoms with a known amount of potassium is 2.7%
      (SD). The uncertainty in the method of body habitus correction (applicable also
      to phantom-based methods) is 1.5% (SD). It is concluded that this new strategy
      provides a sufficiently accurate model for routine clinical use.

PMID- 16912381
TI  - Tilted angle CZT detector for photon counting/energy weighting x-ray and CT
      imaging.
AB  - X-ray imaging with a photon counting/energy weighting detector can provide the
      highest signal to noise ratio (SNR). Scanning slit/multi-slit x-ray image
      acquisition can provide a dose-efficient scatter rejection, which increases SNR.
      Use of a photon counting/energy weighting detector in a scanning slit/multi-slit
      acquisition geometry could provide highest possible dose efficiency in x-ray and
      CT imaging. Currently, the most advanced photon counting detector is the cadmium
      zinc telluride (CZT) detector, which, however, is suboptimal for energy resolved
      x-ray imaging. A tilted angle CZT detector is proposed in this work for
      applications in photon counting/energy weighting x-ray and CT imaging. In tilted
      angle configuration, the x-ray beam hits the surface of the linear array of CZT
      crystals at a small angle. This allows the use of CZT crystals of a small
      thickness while maintaining the high photon absorption. Small thickness CZT
      detectors allow for a significant decrease in the polarization effect in the CZT
      volume and an increase in count rate. The tilted angle CZT with a small thickness
      also provides higher spatial and energy resolution, and shorter charge collection
      time, which potentially enables fast energy resolving x-ray image acquisition. In
      this work, the major performance parameters of the tilted angle CZT detector,
      including its count rate, spatial resolution and energy resolution, were
      evaluated. It was shown that for a CZT detector with a 0.7 mm thickness and 13
      degrees tilting angle, the maximum count rate can be increased by 10.7 times,
      while photon absorption remains >90% at photon energies up to 120 keV. Photon
      counting/energy weighting x-ray imaging using a tilted angle CZT detector was
      simulated. SNR improvement due to optimal photon energy weighting was 23% and 14%
      when adipose contrast element, inserted in soft tissue with 10 cm and 20 cm
      thickness, respectively, was imaged using 5 energy bins and weighting factors
      optimized for the adipose. SNR improvement was 42% and 31% when CaCO(3) contrast
      element, inserted in soft tissue with 10 cm and 20 cm thickness, respectively,
      was imaged using 5 energy bins and weighting factors optimized for CaCO(3). The
      SNRs of the photon counting single-kVp dual-energy subtracted images of CaCO(3)
      and adipose were higher by 2.04 and 2.74 times, respectively, as compared to
      currently used dual-kVp dual-energy subtracted images. Experiments with a CZT
      crystal with 2 mm thickness have shown significant decrease in the tailing effect
      of the CZT pulse spectrum at 59 keV and 122 keV photon energies, when the tilting
      angle configuration was used. Finally, feasibility of the tilted angle CZT
      detector for photon counting cone beam breast CT imaging was demonstrated.

PMID- 16912382
TI  - X-ray imaging optimization using virtual phantoms and computerized observer
      modelling.
AB  - This study develops and demonstrates a realistic x-ray imaging simulator with
      computerized observers to maximize lesion detectability and minimize patient
      exposure. A software package, ViPRIS, incorporating two computational patient
      phantoms, has been developed for simulating x-ray radiographic images. A
      tomographic phantom, VIP-Man, constructed from Visible Human anatomical colour
      images is used to simulate the scattered portion using the ESGnrc Monte Carlo
      code. The primary portion of an x-ray image is simulated using the projection ray
      tracing method through the Visible Human CT data set. To produce a realistic
      image, the software simulates quantum noise, blurring effects, lesions, detector
      absorption efficiency and other imaging artefacts. The primary and scattered
      portions of an x-ray chest image are combined to form a final image for
      computerized observer studies and image quality analysis. Absorbed doses in
      organs and tissues of the segmented VIP-Man phantom were also obtained from the
      Monte Carlo simulations. Approximately 25,000 simulated images and 2,500,000 data
      files were analysed using computerized observers. Hotelling and Laguerre-Gauss
      Hotelling observers are used to perform various lesion detection tasks. Several
      model observer tasks were used including SKE/BKE, MAFC and SKEV. The energy
      levels and fluence at the minimum dose required to detect a small lesion were
      determined with respect to lesion size, location and system parameters.

PMID- 16912383
TI  - K-edge digital subtraction imaging with dichromatic x-ray sources: SNR and dose
      studies.
AB  - The aim of the present work is to analytically evaluate the signal to noise ratio
      (SNR) and the delivered dose in K-edge digital subtraction imaging (KES) using
      two types of x-ray sources: a monochromatic x-ray source (available at
      synchrotron radiation facilities and considered as gold standard) and a quasi
      monochromatic compact source. The energy separation DeltaE between the two
      monochromatic beams is 1 keV and 4 keV for the two sources, respectively. The
      evaluation has been performed for both radiography and computed tomography.
      Different geometries have been studied to mimic clinical situations. In
      mammography, a pathology perfused by a contrast agent has been modelled; in
      angiography, a vessel superimposed to a ventricle or a stand-alone artery
      stenosis has been studied. The SNR and the skin dose have been calculated as a
      function of the detail diameter, the contrast agent (iodine and gadolinium), and
      its concentration in the tissues. Results show that for DeltaE = 4 keV a slightly
      higher delivered dose is required to obtain the same SNR with respect to DeltaE <
      1 keV. A similar study has been performed for KES-CT. Computer simulations of CT
      images performed with Snark software are shown to validate the analytical
      calculations.

PMID- 16912384
TI  - Feasibility and measurement precision of 3D quantitative blood flow mapping of
      the prostate using dynamic contrast-enhanced multi-slice CT.
AB  - We have developed a 3D dynamic contrast-enhanced (DCE) multislice CT protocol
      that covers the complete prostate. The DCE-CT data are subsequently analysed
      using the adiabatic approximation of the tissue homogeneity model resulting in
      five 3D quantitative maps of blood flow, mean transit time, extraction fraction,
      extracellular extravascular space and delay time. The purpose of this study was
      to establish the feasibility of determining these parameters in the prostate with
      a spatial resolution as high as approximately 0.1 cc as well as a good
      measurement precision. The precision of the parameter estimation as a function of
      noise level is determined by a Monte Carlo-based method that simulates the effect
      of noise present in the data. We find that the precision depends on the value of
      the flow and transit time, where a higher value is favourable. At a noise level
      of 4 HU in combination with a peak enhancement in the iliac arteries of
      approximately 300 HU the 95% confidence intervals are sufficiently small to
      discriminate whether a parameter value is above or below a given threshold. We
      have collected and analysed the noise level in the DCE-data of five patients. A
      noise level of 3.8 HU on average can be obtained by averaging to a voxel volume
      of 4.5 x 4.5 x 5 mm(3) = 0.1 cc. Analysis of the parameter maps shows that it is
      feasible to detect both small and large lesions, as well as irregularly shaped
      lesions.

PMID- 16912385
TI  - Physical mechanism of the Schwarzschild effect in film dosimetry--theoretical
      model and comparison with experiments.
AB  - In consideration of the importance of film dosimetry for the dosimetric
      verification of IMRT treatment plans, the Schwarzschild effect or failure of the
      reciprocity law, i.e. the reduction of the net optical density under
      'protraction' or 'fractionation' conditions at constant dose, has been
      experimentally studied for Kodak XOMAT-V (Martens et al 2002 Phys. Med. Biol. 47
      2221-34) and EDR 2 dosimetry films (Djouguela et al 2005 Phys. Med. Biol. 50 N317
      N321). It is known that this effect results from the competition between two
      solid-state physics reactions involved in the latent-image formation of the AgBr
      crystals, the aggregation of two Ag atoms freshly formed from Ag(+) ions near
      radiation-induced occupied electron traps and the spontaneous decomposition of
      the Ag atoms. In this paper, we are developing a mathematical model of this
      mechanism which shows that the interplay of the mean lifetime tau of the Ag atoms
      with the time pattern of the irradiation determines the magnitude of the observed
      effects of the temporal dose distribution on the net optical density. By
      comparing this theory with our previous protraction experiments and recent
      fractionation experiments in which the duration of the pause between fractions
      was varied, a value of the time constant tau of roughly 10 s at room temperature
      has been determined for EDR 2. The numerical magnitude of the Schwarzschild
      effect in dosimetry films under the conditions generally met in radiotherapy
      amounts to only a few per cent of the net optical density (net OD), so that it
      can frequently be neglected from the viewpoint of clinical applications. But
      knowledge of the solid-state physical mechanism and a description in terms of a
      mathematical model involving a typical time constant of about 10 s are now
      available to estimate the magnitude of the effect should the necessity arise,
      i.e. in cases of large fluctuations of the temporal pattern of film exposure.

PMID- 16912386
TI  - Deformable registration of the planning image (kVCT) and the daily images (MVCT)
      for adaptive radiation therapy.
AB  - The incorporation of daily images into the radiotherapy process leads to adaptive
      radiation therapy (ART), in which the treatment is evaluated periodically and the
      plan is adaptively modified for the remaining course of radiotherapy. Deformable
      registration between the planning image and the daily images is a key component
      of ART. In this paper, we report our researches on deformable registration
      between the planning kVCT and the daily MVCT image sets. The method is based on a
      fast intensity-based free-form deformable registration technique. Considering the
      noise and contrast resolution differences between the kVCT and the MVCT, an 'edge
      preserving smoothing' is applied to the MVCT image prior to the deformable
      registration process. We retrospectively studied daily MVCT images from
      commercial TomoTherapy machines from different clinical centers. The data set
      includes five head-neck cases, one pelvis case, two lung cases and one prostate
      case. Each case has one kVCT image and 20-40 MVCT images. We registered the MVCT
      images with their corresponding kVCT image. The similarity measures and visual
      inspections of contour matches by physicians validated this technique. The
      applications of deformable registration in ART, including 'deformable dose
      accumulation', 'automatic re-contouring' and 'tumour growth/regression
      evaluation' throughout the course of radiotherapy are also studied.

PMID- 16912387
TI  - Assessment of absorbed dose to thyroid, parotid and ovaries in patients
      undergoing Gamma Knife radiosurgery.
AB  - Stereotactic radiosurgery was originally introduced by Lars Leksell in 1951. This
      treatment refers to the noninvasive destruction of an intracranial target
      localized stereotactically. The purpose of this study was to identify the dose
      delivered to the parotid, ovaries, testis and thyroid glands during the Gamma
      Knife radiosurgery procedure. A three-dimensional, anthropomorphic phantom was
      developed using natural human bone, paraffin and sodium chloride as the
      equivalent tissue. The phantom consisted of a thorax, head and neck and hip. In
      the natural places of the thyroid, parotid (bilateral sides) and ovaries
      (midline), some cavities were made to place TLDs. Three TLDs were inserted in a
      batch with 1 cm space between the TLDs and each batch was inserted into a single
      cavity. The final depth of TLDs was 3 cm from the surface for parotid and thyroid
      and was 15 cm for the ovaries. Similar batches were placed superficially on the
      phantom. The phantom was gamma irradiated using a Leksell model C Gamma Knife
      unit. Subsequently, the same batches were placed superficially over the thyroid,
      parotid, testis and ovaries in 30 patients (15 men and 15 women) who were
      undergoing radiosurgery treatment for brain tumours. The mean dosage for treating
      these patients was 14.48 +/- 3.06 Gy (10.5-24 Gy) to a mean tumour volume of
      12.30 +/- 9.66 cc (0.27-42.4 cc) in the 50% isodose curve. There was no
      significant difference between the superficial and deep batches in the phantom
      studies (P-value < 0.05). The mean delivered doses to the parotid, thyroid,
      ovaries and testis in human subjects were 21.6 +/- 15.1 cGy, 9.15 +/- 3.89 cGy,
      0.47 +/- 0.3 cGy and 0.53 +/- 0.31 cGy, respectively. The data can be used in
      making decisions for special clinical situations such as treating pregnant
      patients or young patients with benign lesions who need radiosurgery for
      eradication of brain tumours.

PMID- 16912388
TI  - Investigating the accuracy of the FLUKA code for transport of therapeutic ion
      beams in matter.
AB  - In-beam positron emission tomography (PET) is currently used for monitoring the
      dose delivery at the heavy ion therapy facility at GSI Darmstadt. The method is
      based on the fact that carbon ions produce positron emitting isotopes in
      fragmentation reactions with the atomic nuclei of the tissue. The relation
      between dose and beta(+)-activity is not straightforward. Hence it is not
      possible to infer the delivered dose directly from the PET distribution. To
      overcome this problem and enable therapy monitoring, beta(+)-distributions are
      simulated on the basis of the treatment plan and compared with the measured ones.
      Following the positive clinical impact, it is planned to apply the method at
      future ion therapy facilities, where beams from protons up to oxygen nuclei will
      be available. A simulation code capable of handling all these ions and predicting
      the irradiation-induced beta(+)-activity distributions is desirable. An
      established and general purpose radiation transport code is preferred. FLUKA is a
      candidate for such a code. For application to in-beam PET therapy monitoring, the
      code has to model with high accuracy both the electromagnetic and nuclear
      interactions responsible for dose deposition and beta(+)-activity production,
      respectively. In this work, the electromagnetic interaction in FLUKA was adjusted
      to reproduce the same particle range as from the experimentally validated
      treatment planning software TRiP, used at GSI. Furthermore, projectile
      fragmentation spectra in water targets have been studied in comparison to
      available experimental data. Finally, cross sections for the production of the
      most abundant fragments have been calculated and compared to values found in the
      literature.

PMID- 16912389
TI  - Radiobiological modelling of dose-gradient effects in low dose rate, high dose
      rate and pulsed brachytherapy.
AB  - This paper presents a generalization of a previously published methodology which
      quantified the radiobiological consequences of dose-gradient effects in
      brachytherapy applications. The methodology uses the linear-quadratic (LQ)
      formulation to identify an equivalent biologically effective dose (BED(eq))
      which, if applied uniformly to a specified tissue volume, would produce the same
      net cell survival as that achieved by a given non-uniform brachytherapy
      application. Multiplying factors (MFs), which enable the equivalent BED for an
      enclosed volume to be estimated from the BED calculated at the dose reference
      surface, have been calculated and tabulated for both spherical and cylindrical
      geometries. The main types of brachytherapy (high dose rate (HDR), low dose rate
      (LDR) and pulsed (PB)) have been examined for a range of radiobiological
      parameters/dimensions. Equivalent BEDs are consistently higher than the BEDs
      calculated at the reference surface by an amount which depends on the treatment
      prescription (magnitude of the prescribed dose) at the reference point. MFs are
      closely related to the numerical BED values, irrespective of how the original BED
      was attained (e.g., via HDR, LDR or PB). Thus, an average MF can be used for a
      given prescribed BED as it will be largely independent of the assumed
      radiobiological parameters (radiosensitivity and alpha/beta) and standardized
      look-up tables may be applicable to all types of brachytherapy treatment. This
      analysis opens the way to more systematic approaches for correlating physical and
      biological effects in several types of brachytherapy and for the improved
      quantitative assessment and ranking of clinical treatments which involve a
      brachytherapy component.

PMID- 16912391
TI  - Mechanobiology and cartilage engineering: the underlying pathophysiological
      phenomena.

PMID- 16912390
TI  - Variability among polysulphone calibration curves.
AB  - Within an epidemiological study regarding the correlation between skin
      pathologies and personal ultraviolet (UV) exposure due to solar radiation, 14
      field campaigns using polysulphone (PS) dosemeters were carried out at three
      different Italian sites (urban, semi-rural and rural) in every season of the
      year. A polysulphone calibration curve for each field experiment was obtained by
      measuring the ambient UV dose under almost clear sky conditions and the
      corresponding change in the PS film absorbance, prior and post exposure. Ambient
      UV doses were measured by well-calibrated broad-band radiometers and by
      electronic dosemeters. The dose-response relation was represented by the typical
      best fit to a third-degree polynomial and it was parameterized by a coefficient
      multiplying a cubic polynomial function. It was observed that the fit curves
      differed from each other in the coefficient only. It was assessed that the
      multiplying coefficient was affected by the solar UV spectrum at the Earth's
      surface whilst the polynomial factor depended on the photoinduced reaction of the
      polysulphone film. The mismatch between the polysulphone spectral curve and the
      CIE erythemal action spectrum was responsible for the variability among
      polysulphone calibration curves. The variability of the coefficient was related
      to the total ozone amount and the solar zenith angle. A mathematical explanation
      of such a parameterization was also discussed.

PMID- 16912392
TI  - Force-mediated dissociation of proteoglycan aggregate in articular cartilage.
AB  - Proteoglycan aggregate is the primary component in articular cartilage
      responsible for resisting compressive loading. It consists of a core molecule of
      hyaluronan and a number of side chains of aggrecan bound to hyaluronan non
      covalently. The loss of aggrecan from articular cartilage is considered to be a
      major factor in the development of osteoarthritis. Though enzymatic digestion of
      aggrecan is believed to be responsible for the release of aggrecan from
      osteoarthritic cartilage, other mechanisms, such as direct force-mediated
      detachment of aggrecan from hyaluronan may also be involved. In this study, the
      rupture force of the single bond between hyaluronan and aggrecan in articular
      cartilage was directly quantified using experimental measurement and Monte Carlo
      simulation. Low rupture force of this bond, as determined in this study suggested
      a possible direct force-mediated detachment of aggrecan from proteoglycan
      aggregate in osteoarthritic cartilage.

PMID- 16912393
TI  - Static and dynamic compression regulate cartilage metabolism of PRoteoGlycan 4
      (PRG4).
AB  - The boundary lubrication function of articular cartilage is mediated in part by
      molecules at the articular surface and in synovial fluid, encoded by Prg4. The
      objective of this study was to determine whether static and dynamic compression
      regulate PRG4 biosynthesis by cartilage explants. Articular cartilage disks were
      harvested to include the articular surface from immature bovines. Some disks were
      subjected to 24 h (day 1) of loading, followed by 72 h (days 2-4) of free
      swelling culture to assess chondrocyte responses following unloading. Loading
      consisted of 6 or 100 kPa of static compression, with or without superimposed
      dynamic compression (10 or 300 kPa peak amplitude, 0.01 Hz). Other disks were
      cultured free-swelling as controls. PRG4 secretion into culture medium was
      inhibited by all compression protocols during day 1. Following unloading,
      cartilage previously subjected to dynamic compression to 300 kPa exhibited a
      rebound effect, secreting more PRG4 than did controls, while cartilage previously
      subjected to 100 kPa static loading secreted less PRG4. Immunohistochemistry
      revealed that all compression protocols also affected the number of cells
      expressing PRG4. The paradigm that mechanical stimuli regulate biosynthesis in
      cartilage appears operative not only for load bearing matrix constituents, but
      also for PRG4 molecules mediating lubrication.

PMID- 16912394
TI  - Intracellular mechanics and mechanotransduction associated with chondrocyte
      deformation during pipette aspiration.
AB  - The present study utilised pipette aspiration and simultaneous confocal
      microscopy to test the hypothesis that chondrocyte deformation is associated with
      distortion of intracellular organelles and activation of calcium signalling.
      Aspiration pressure was applied to isolated articular chondrocytes in increments
      of 2 cm of water every 60 seconds up to a maximum of 10 cm of water. At each
      pressure increment, confocal microscopy was used to visualise the mitochondria
      and nucleus labelled with JC-1 and Syto-16, respectively. To investigate
      intracellular calcium signalling, separate cells were labelled with Fluo 4,
      rapidly aspirated to 5 cm of water and then imaged for 5 minutes at a tare
      pressure of 0.1 cm of water. Partial cell aspiration was associated with
      distortion of the mitochondrial network, elongation of the nucleus and movement
      towards the pipette mouth. Treatment with cytochalasin D or nocodazole produced
      an increase in cell aspiration indicating that both the actin microfilaments and
      microtubules provide mechanical integrity to the cell. When the data was
      normalised to account for the increased cell deformation, both actin
      microfilaments and microtubules were shown to be necessary for strain transfer to
      the intracellular organelles. Mitochondria and nucleus deformation may both be
      involved in chondrocyte mechanotransduction as well as cellular and intracellular
      mechanics. In addition, pipette aspiration induced intracellular calcium
      signalling which may also form part of a mechanotransduction pathway.
      Alternatively calcium mobilisation may serve to modify actin polymerisation,
      thereby changing cell mechanics and membrane rigidity in order to facilitate
      localised cell deformation. These findings have important implications for our
      understanding of cell mechanics and mechanotransduction as well as interpretation
      and modelling of pipette aspiration data.

PMID- 16912395
TI  - The effect of hydrodynamic shear on 3D engineered chondrocyte systems subject to
      direct perfusion.
AB  - Bioreactors allowing direct-perfusion of culture medium through tissue-engineered
      constructs may overcome diffusion limitations associated with static culturing,
      and may provide flow-mediated mechanical stimuli. The hydrodynamic stress imposed
      on cells within scaffolds is directly dependent on scaffold microstructure and on
      bioreactor configuration. Aim of this study is to investigate optimal shear
      stress ranges and to quantitatively predict the levels of hydrodynamic shear
      imposed to cells during the experiments. Bovine articular chondrocytes were
      seeded on polyestherurethane foams and cultured for 2 weeks in a direct perfusion
      bioreactor designed to impose 4 different values of shear level at a single flow
      rate (0.5 ml/min). Computational fluid dynamics (CFD) simulations were carried
      out on reconstructions of the scaffold obtained from micro-computed tomography
      images. Biochemistry analyses for DNA and sGAG were performed, along with
      electron microscopy. The hydrodynamic shear induced on cells within constructs,
      as estimated by CFD simulations, ranged from 4.6 to 56 mPa. This 12-fold increase
      in the level of applied shear stress determined a 1.7-fold increase in the mean
      content in DNA and a 2.9-fold increase in the mean content in sGAG. In contrast,
      the mean sGAG/DNA ratio showed a tendency to decrease for increasing shear
      levels. Our results suggest that the optimal condition to favour sGAG synthesis
      in engineered constructs, at least at the beginning of culture, is direct
      perfusion at the lowest level of hydrodynamic shear. In conclusion, the presented
      results represent a first attempt to quantitatively correlate the imposed
      hydrodynamic shear level and the invoked biosynthetic response in 3D engineered
      chondrocyte systems.

PMID- 16912396
TI  - Calcium/calmodulin-dependent protein kinase II in human articular chondrocytes.
AB  - Mechanical stimuli are known to have major influences on chondrocyte function.
      The molecular events that regulate chondrocyte responses to mechanical
      stimulation have been the subject of much study. Using an in vitro experimental
      system we have identified mechanotransduction pathways that control molecular and
      biochemical responses of human articular chondrocytes to cyclical mechanical
      stimulation, and how these responses differ in cells isolated from diseased
      cartilage. We have previously shown that mechanical stimulation of normal
      articular chondrocytes leads to a cell membrane hyperpolarisation. Within 1 hour
      following mechanical stimulation there is an increase in aggrecan mRNA levels.
      These responses are mediated via alpha5beta1 integrins, the neuropeptides
      substance P and NMDA, and the cytokine interleukin-4. In OA chondrocytes
      mechanical stimulation leads to cell membrane depolarisation, but no change in
      aggrecan mRNA at 1 hour. The depolarisation response is mediated via alpha5beta1
      integrins, substance P and interleukin-4, but the cells show an altered response
      to NMDA. Having identified that the NMDA receptor is present in human articular
      cartilage and may play an important role in a chondroprotective
      mechanotransduction pathway, we were interested in whether other components
      associated with NMDA signalling may be involved in the chondrocyte
      mechanotransduction pathways. One such component is calcium/calmodulin-dependent
      protein kinase II (CaMKII). CaMKII mediates many cellular responses to elevated
      Ca2+ in a wide variety of cells and tissues. It is involved in the regulation of
      ion channels, cytoskeletal dynamics, gene transcription, neurotransmitter
      synthesis, insulin secretion, and cell division. CaMKII also shows a broad
      substrate specificity and is abundant in brain tissue, indicating that this
      kinase may play a number of roles in the functioning of the central nervous
      system. This kinase has been studied extensively in brain, but there is only a
      limited understanding of CaMKII in other tissues. CAMKII has four subunit
      isoforms (alpha,beta,gamma,delta). The alpha- and beta-isoforms have narrow
      distributions restricted mainly to neuronal tissues, but the gamma- and delta
      isoforms are ubiquitously expressed within neuronal and non-neuronal tissues. The
      aim of this study was to investigate the expression of CaMKII in normal and OA
      cartilage and chondrocytes, and whether this enzyme is involved in the response
      of chondrocytes to cyclical mechanical stimuli. Reverse transcriptase-polymerase
      chain reaction (RT-PCR), using primers specific for the different CaMKII
      isoforms, was carried out to assess which isoforms are expressed in human
      articular chondrocytes. To assess whether CaMKII is expressed in human articular
      chondrocytes at the protein level, cultured chondrocytes were extracted and
      analysed by Western blotting using a pan-CaMKII antibody. Immunohistochemistry
      was carried out to investigate whether CaMKII is expressed by human articular
      chondrocytes in vivo. Frozen sections of normal, OA and ankle cartilage were
      incubated for one hour with CaMKII antibody and visualised using ABC and DAB. To
      assess the role of CaMKII in the mechanotransduction responses of normal and OA
      chondrocytes, human normal and OA articular chondrocytes were mechanically
      stimulated at 0.33 Hz, or by addition of recombinant IL-4 for 20 minutes. Cell
      responses to these stimuli, in the absence or presence of an inhibitor of CaMKII
      were assessed by measuring changes in cell membrane potential or changes in
      relative levels of aggrecan mRNA compared with the housekeeping gene GAPDH.
      Normal, OA, and ankle chondrocytes expressed the gamma and delta isoforms of
      CaMKII mRNA, but not the alpha and beta isoforms as demonstrated by RT-PCR.
      Western blotting showed a band at approximately 60 kDa consistent with the
      expression of CaMKII. Immunohistochemistry revealed the positive staining in the
      middle and deep zones, but not the superficial zone, of normal, OA, and ankle
      cartilage. The presence of a CaMKII inhibitor inhibits the membrane
      hyperpolarisation response and upregulation of aggrecan mRNA in normal
      chondrocytes following mechanical stimulation, but has no effect on the
      hyperpolarisation response to recombinant IL4. The depolarisation response of OA
      chondrocytes to mechanical stimulation is unaffected by the presence of the
      CaMKII inhibitor. The CaMKII isoforms gamma and delta are expressed in both
      normal and OA chondrocytes, both in vitro and in vivo, but are only involved in
      the response of normal chondrocytes to mechanical stimulation. This response is
      upstream of the effect of IL4. These findings are consistent with previous
      findings for the NMDA receptor, and suggest that dysregulation of NMDA-CaMKII
      signalling may be important in onset and progression of osteoarthritis.

PMID- 16912397
TI  - Poroelastic numerical modelling of natural and engineered cartilage based on in
      vitro tests.
AB  - The mechanisms underlying the ability of articular cartilage to withstand and
      distribute the loads applied across diarthrodial joints have been widely studied.
      Experimental tests have been done under several configurations to reveal the
      tissue response to mechanical stimuli, and theoretical models have been developed
      for the interpretation of the experimental results. The experiments demonstrated
      that the tissue is non-linear with strain, both in tension and in compression,
      non-linear with direction of stimulus, anisotropic in tension and compression,
      non-homogeneous with depth, resulting in depth dependent mechanical properties,
      and presents fluid dependent and fluid independent viscoelasticity. None of the
      models up to now developed is able to describe the whole set of responses of such
      a complex tissue. The purpose of this study was to develop a combined
      experimental-numerical approach for the proper description of the cartilage
      response under confined and unconfined compression. We defined a series of
      experimental tests to be performed on disks of natural and engineered cartilage
      and we developed a numerical model for cartilage, based on the biphasic theory,
      which potentially includes the tension-compression non-linearity, the strain non
      linearity and the fluid independent viscoelasticity. The model successfully
      simulated the confined and unconfined compression experiments performed on disks
      of natural and engineered cartilage, and was also used to identify parameters of
      difficult experimental evaluation, such as the collagen stiffness and the
      permeability. In conclusion, the use of our model in combination with
      biomechanical experimental testing seems a valuable tool to analyze the
      mechanical properties of natural cartilage and the biofunctionality of tissue
      engineered cartilage.

PMID- 16912398
TI  - Mechanical responses and integrin associated protein expression by human ankle
      chondrocytes.
AB  - Metabolic, biochemical and biomechanical differences between ankle and knee joint
      cartilage and chondrocytes including resistance to the effects of catabolic
      cytokines and fibronectin fragments may be relevant to differences in prevalence
      of OA in these joints. Although there is increasing information available on how
      chondrocytes from knee and hip joint cartilage recognise and respond to
      mechanical stimuli, knowledge of mechanotransduction in ankle joint chondrocytes
      is limited. This study was undertaken to (i) establish whether the response of
      normal ankle joint derived chondrocytes to mechanical stimulation in vitro was
      similar to that of normal and osteoarthritic knee joint derived chondrocytes and
      (ii) to investigate whether these chondrocytes showed differences in expression
      of integrin associated regulatory and signalling molecules. Unlike normal knee
      joint chondrocytes, ankle joint chondrocytes did not show an increase in relative
      levels of aggrecan mRNA when mechanically stimulated. No obvious change in
      protein tyrosine phosphorylation was seen in ankle chondrocytes subsequent to
      mechanical stimulation but these cells expressed elevated levels of tyrosine
      phosphorylated proteins at rest when compared to normal knee joint chondrocytes.
      Ankle joint chondrocytes showed an increase in protein kinase B phosphorylation
      following 1 min 0.33 Hz stimulation which was inhibited by the presence of
      antibodies to alpha5beta1 integrin. Ankle joint chondrocytes appeared to show
      significant differences in levels of the integrin-associated proteins CD98, CD147
      and galectin 3, PKCgamma and differences in responses to glutamate were seen.
      Chondrocytes from ankle and knee joint cartilage respond differently to 0.33 Hz
      mechanical stimulation. This may be related to modified integrin-dependent
      mechanotransduction as a result of changes in expression of integrin regulatory
      molecules such as CD98 or differential expression and function of downstream
      components of the mechanotransduction pathway such as PKC or NMDA receptors.

PMID- 16912399
TI  - Chondrocyte gene expression under applied surface motion.
AB  - A cartilage bioreactor has been designed that is intended to approximate the
      kinematics of natural joints and allows for functional cartilage tissue
      engineering studies. In particular, interface motion can be generated by
      oscillation of a ball over the surface of a construct. The present study
      investigated the specific effect of applied articular motion on the gene
      expression of chondrocytes cultured in 3D scaffolds, with a particular emphasis
      on different superficial zone protein (SZP)/lubricin transcripts. Cylindrical
      porous polyurethane scaffolds were seeded with bovine articular chondrocytes and
      subjected to dynamic compression, with or without articulation against a ceramic
      hip ball. Articular motion markedly up-regulated the mRNA expression of the four
      previously described and two newly identified SZP/lubricin isoforms and of
      cartilage oligomeric matrix protein (COMP), and, to a lesser extent, aggrecan,
      type II collagen and TIMPs, while axial compression alone had no effect on the
      chondrocytes' gene expression levels. These results demonstrate the beneficial
      effect of articular motion not only for stimulation of important lubricating
      molecules, but also for the preservation of the chondrocytic phenotype.

PMID- 16912400
TI  - Ultrasound stimulates proteoglycan synthesis in bovine primary chondrocytes.
AB  - Mechanical forces can stimulate the production of extracellular matrix molecules.
      We tested the efficacy of ultrasound to increase proteoglycan synthesis in bovine
      primary chondrocytes. The ultrasound-induced temperature rise was measured and
      its contribution to the synthesis was investigated using bare heat stimulus.
      Chondrocytes from five cellular isolations were exposed in triplicate to
      ultrasound (1 MHz, duty cycle 20%, pulse repetition frequency 1 kHz) at average
      intensity of 580 mW/cm2 for 10 minutes daily for 1-5 days. Temperature evolution
      was recorded during the sonication and corresponding temperature history was
      created using a controllable water bath. This exposure profile was used in 10
      minute-long heat treatments of chondrocytes. Heat shock protein 70 (Hsp70) levels
      after one-time treatment to ultrasound and heat was analyzed by Western blotting,
      and proteoglycan synthesis was evaluated by 35S-sulfate incorporation. Ultrasound
      treatment did not induce Hsp70, while heat treatment caused a slight heat stress
      response. Proteoglycan synthesis was increased approximately 2-fold after 3-4
      daily ultrasound stimulations, and remained at that level until day 5 in
      responsive cell isolates. However, chondrocytes from one donor cell isolation out
      of five remained non-responsive. Heat treatment alone did not increase
      proteoglycan synthesis. In conclusion, our study confirms that pulsed ultrasound
      stimulation can induce proteoglycan synthesis in chondrocytes.

PMID- 16912401
TI  - Diurnal fluid expression and activity of intervertebral disc cells.
AB  - The intervertebral discs are large cartilaginous structures situated between the
      vertebral bodies, occupying around one third of the length of the spinal column.
      They act as the joints of the spine and carry mechanical load arising from body
      weight and muscle activity. Loads change with every alteration of posture and
      activity and the discs thus undergo a diurnal loading pattern with high loads on
      the discs during the day's activity and low loads on it at night during rest. As
      the disc is an osmotic system, around 25% of the disc's fluid is expressed and re
      imbibed during each diurnal cycle with consequent changes in the osmotic
      environment of the disc cells. Here, present information on the effect of osmotic
      changes in disc cell metabolism is reviewed; results indicate that prevailing
      osmolarity is a powerful regulator of disc cell activity.

PMID- 16912402
TI  - A mandibular propulsive appliance modulates collagen-binding integrins
      distribution in the young rat condylar cartilage.
AB  - We have previously shown that a mandibular propulsive appliance (MPA) stimulates
      cell proliferation and the synthesis of growth factors in the rat condylar
      cartilage. The aim of this study was to evaluate the effects of a MPA in the
      distribution of the integrin subunits alpha1 and alpha2 in this cartilage. Twenty
      eight days-old male Wistar rats were divided into treated (T) and age-matched
      control groups (C). Treated rats wore the appliance during 3, 5, 7, 9, 11, 15,
      20, 30 and 35 days. The condyles were fixed, decalcified and paraffin-embedded.
      The distribution of alpha1 and alpha2 was studied by immunohistochemistry. Alpha1
      distribution was uniform along the cartilage, increasing in 48 days-old rats
      (C20). Treated animals anticipated this increase to the age of 36 days (T9). The
      number of alpha2-positive cells was increased in C9 in the anterior condylar
      region, in C9 and C20 in the middle region and showed no differences in the
      posterior region. The MPA apparently abolished all variations, leading to a
      single increase at T30 in all regions. These results suggest that integrins
      containing the alpha1 and alpha2 subunits are modulated by forces promoted by the
      MPA, participating of the biological response to this therapy.

PMID- 16912403
TI  - Modulation of proteoglycan production by cyclic tensile stretch in intervertebral
      disc cells through a post-translational mechanism.
AB  - Proteoglycan production is one of the major extracellular matrix components
      implicated in the dynamic process of intervertebral disc degeneration. Mechanical
      stress is an important modulator of the degeneration, but the underlying
      molecular mechanism at the proteoglycan level remains unclear. The aim of this
      work was to study the regulation of proteoglycan production by cyclic tensile
      stretch applied to intervertebral disc annulus fibrosus cells. Matrix
      metalloproteinases do not seem to be implicated in the regulation of proteoglycan
      production. By contrast, nitrite oxide production is induced by cyclic tensile
      stretch, in a time, intensity, and frequency dependant manner. Using a non
      specific nitric oxide synthases inhibitor [NG-methyl-L-arginine (L-NMA)], we
      suppress totally the inhibition of proteoglycan production induced by cyclic
      tensile stretch suggesting the implication of nitric oxide synthases in the
      observed phenomenon. Introducing the transcriptional inhibitor 5,6-dichloro-1
      beta-D-ribofuranosylbenzimidazole or a more specific inhibitor of nitric oxide
      synthases II [N-iminoethyl-L-lysine (L-NIL)] did not affect the decreased
      proteoglycan production, which suggests a post-translational regulation. In
      contrast, N-omega nitro-L-arginine (L-NNA) a more specific inhibitor of NOS I and
      III abrogated the cyclic tensile stretch-dependant inhibition of proteoglycan
      production. These results suggest that cyclic tensile stretch regulates
      proteoglycan production through a post-translational mechanism involving nitrite
      oxide. This result could be of interest in the development of local therapeutic
      strategies aimed at controlling intervertebral disc degeneration.

PMID- 16912404
TI  - Mandibular repositioning modulates IGFBP-3, -4, -5 and -6 expression in the
      mandibular condylar cartilage of young rats.
AB  - Functional orthopedic appliances correct dental malocclusion partially by
      exerting indirect mechanical stimulus on the condylar cartilage, modulating
      growth and the adaptation of orofacial structures. However, the exact nature of
      the biological responses to this therapy is not well understood. Insulin-like
      growth factors I and II (IGF-I and II) are important local factors during growth
      and differentiation in the condylar cartilage [D. Hajjar, M.F. Santos and E.T.
      Kimura, Propulsive appliance stimulates the synthesis of insulin-like growth
      factors I and II in the mandibular condylar cartilage of young rats, Arch. Oral
      Biol. 48 (2003), 635-642]. The bioefficacy of IGFs at the cellular level is
      modulated by IGF binding proteins (IGFBP). The aim of this study was to verify
      the mRNA and protein expression of IGFBP-3, IGFBP-4, IGFBP-5 and IGFBP-6 in the
      condylar cartilage of young male Wistar rats that used a mandibular propulsive
      appliance for 3, 9, 15, 20, 30 or 35 days. For this purpose, sagittal sections of
      decalcified and paraffin-embedded condyles were submitted to immunohistochemistry
      and the condylar cartilage to RT-PCR. The control group showed a gradual increase
      in the protein expression of all IGFBPs, except IGFBP-4. Following use of the
      appliance, IGFBP-3 and IGFBP-6 expression decreased in the early stage of the
      treatment. At 20 days of treatment there was a decline in the IGFs and IGFBP-3,
      IGFBP-4 and IGFBP-5 expression and at 30 days there was a peak in the IGFs and
      all IGFBPs expression except for IGFBP-3 where the peak was observed in the
      control animals. The expression patterns of all IGFBPs in the condylar cartilage
      were similar. The modulation of IGFBP-3, -4, -5 and -6 expression in the condylar
      cartilage in response to the propulsive appliance suggests that those peptides
      are involved in the mandibular adaptation during this therapy.

PMID- 16912405
TI  - Physical signals and solute transport in human intervertebral disc during
      compressive stress relaxation: 3D finite element analysis.
AB  - A 3D finite element model for charged hydrated soft tissues containing
      charged/uncharged solutes was developed based on the multi-phasic mechano
      electrochemical mixture theory (Lai et al., J. Biomech. Eng. 113 (1991), 245-258;
      Gu et al., J. Biomech. Eng. 120 (1998), 169-180). This model was applied to
      analyze the mechanical, chemical and electrical signals within the human
      intervertebral disc during an unconfined compressive stress relaxation test. The
      effects of tissue composition [e.g., water content and fixed charge density
      (FCD)] on the physical signals and the transport rate of fluid, ions and
      nutrients were investigated. The numerical simulation showed that, during disc
      compression, the fluid pressurization was more pronounced at the center (nucleus)
      region of the disc while the effective (von Mises) stress was higher at the outer
      (annulus) region. Parametric analyses revealed that the decrease in initial
      tissue water content (0.7-0.8) increased the peak stress and relaxation time due
      to the reduction of permeability, causing greater fluid pressurization effect.
      The electrical signals within the disc were more sensitive to FCD than tissue
      porosity, and mechanical loading affected the large solute (e.g., growth factor)
      transport significantly, but not for small solute (e.g., glucose). Moreover, this
      study confirmed that the interstitial fluid pressurization plays an important
      role in the load support mechanism of IVD by sharing more than 40% of the total
      load during disc compression. This study is important for understanding disc
      biomechanics, disc nutrition and disc mechanobiology.

PMID- 16912406
TI  - Contraction of collagen gels seeded with tendon cells.
AB  - Knowledge of the adaptation of the soft tissue to mechanical factors and
      biomolecules would be essential to better understand the mechanism of tendon
      injury and to improve the outcome of tendon repair. The responses to these
      factors could be different for the distinct types of cells in the tendon: cells
      from the tendon sheath, fibroblasts from the epitenon surface, or fibroblasts
      from the internal endotenon. In this study, we examined the mechanical and
      histological characteristics of the rate of contraction of the collagen gel
      seeded with epitenon and endotenon fibroblasts. The rate of contraction and the
      mechanical property of the contracted construct depend on the gel concentration
      and also the treatment of TGF-beta1.

PMID- 16912407
TI  - Beneficial actions of hyaluronan (HA) on arthritic joints: effects of molecular
      weight of HA on elasticity of cartilage matrix.
AB  - Hyaluronan (HA) has viscoelastic, anti-inflammatory and protective actions in
      joint tissues, and is being widely used for treatment of OA and RA patients.
      However, the mechanisms underlying the pharmacological action of HA on OA and RA
      have not been fully understood. In this article, we review the molecular weight
      dependent, anti-inflammatory actions of HA preparations - produced in Japan - in
      joint tissues, and show that the molecular weight of HA, but not its
      concentration, is crucial for maintenance of cartilage elasticity.

PMID- 16912408
TI  - Mechanical regulation of secondary chondrogenesis.
AB  - The development of the skull is characterised by its dependence upon epigenetic
      influences. One of the most important of these is secondary chondrogenesis, which
      occurs following ossification within certain membrane bone periostea, as a result
      of biomechanical articulation. We have studied the genesis, character and
      function of the secondary chondrocytes of the quadratojugal of the chick between
      embryonic days 11 and 14. Analysis of gene expression revealed that secondary
      chondrocytes formed coincident with Sox9 upregulation from a precursor population
      expressing Cbfa1/Runx2: a reversal of the normal sequence. Such secondary
      chondrocytes rapidly acquired a phenotype that is a compound of prehypertrophic
      and hypertrophic chondrocytes, exited from the cell cycle and upregulated Ihh.
      Pulse and pulse/chase experiments with BrdU confirmed the germinal region as the
      highly proliferative source of the secondary chondrocytes, which formed by
      division of chondrocyte-committed precursors. By blocking Hh signalling in
      explant cultures we show that the enhanced proliferation of the germinal region
      surrounding the secondary chondrocytes derives from this Ihh source.
      Additionally, in vitro studies on membrane bone periosteal cells (nongerminal
      region) demonstrated that these cells can also respond to Ihh, and do so both by
      enhanced proliferation and precocious osteogenesis. Despite the pro-osteogenic
      effects of Ihh on periosteal cell differentiation, mechanical articulation of the
      quadratojugal/quadrate joint in explant culture revealed a negative role for
      articulation in the regulation of osteocalcin by germinal region descendants.
      Thus, the mechanical stimulus that is the spur to secondary chondrocyte formation
      appears able to override the osteogenic influence of Ihh on the periosteum, but
      does not interfere with the cell cycle-promoting component of Hh signalling.

PMID- 16912409
TI  - Influence of mechanical stress on cell viability.
AB  - The cartilage is a hydrated connective tissue in joints that withstands and
      distributes mechanical forces. The chondrocytes utilize mechanical signals to
      regulate their metabolic activity through complex biological and biophysical
      interactions with the extracellular matrix (ECM). The aim of this work was to
      study the influence of mechanical stress on cells behavior cultured in 3D
      biosystems (alginate and alginate supplemented with hyaluronate). After
      mechanical stimulation, cell viability and cell death process were the main
      studied parameters. Our results indicated that viability and cell cycle
      progression were inhibited under mechanical stimulation, as far as the
      extracellular matrix was not yet synthesized. In contrast, on day 21, the
      mechanical stimulation had positive effect on these parameters.

PMID- 16912410
TI  - Quantification of subchondral bone changes in a murine osteoarthritis model using
      micro-CT.
AB  - In the past few years there has been a considerable interest in the role of bone
      in osteoarthritis. Despite the increasing evidence of the involvement of bone in
      osteoarthritis, it remains very difficult to attribute the cause or effect of
      changes in subchondral bone to the process of osteoarthritis. Although
      osteoarthritis in mice provides a useful model to study changes in the
      subchondral bone, detailed quantification of these changes is lacking. Therefore,
      the goal of this study was to quantify subchondral bone changes in a murine
      osteoarthritis model by use of micro-computed tomography (micro-CT). We induced
      osteoarthritis-like characteristics in the knee joints of mice using collagenase
      injections, and after four weeks we calculated various 3D morphometric parameters
      in the epiphysis of the proximal tibia. The collagenase injections caused
      cartilage damage, visible in histological sections, particularly on the medial
      tibial plateau. Micro-CT analysis revealed that the thickness of the subchondral
      bone plate was decreased both at the lateral and the medial side. The trabecular
      compartment demonstrated a small but significant reduction in bone volume
      fraction compared to the contralateral control joints. Trabeculae in the
      collagenase-injected joints were thinner but their shape remained rod-like.
      Furthermore, the connectivity between trabeculae was reduced and the trabecular
      spacing was increased. In conclusion, four weeks after induction of
      osteoarthritis in the murine knee subtle but significant changes in subchondral
      bone architecture could be detected and quantified in 3D with micro-CT analysis.

PMID- 16912411
TI  - Subchondral bone and ligament changes precede cartilage degradation in guinea pig
      osteoarthritis.
AB  - There is increasing recognition that osteoarthritis (OA) is a complex disease
      involving the whole synovial joint, rather than the articular cartilage alone,
      however its aetiology and pathogenesis is not understood. Our initial studies
      revealed elevated turnover of bone and ligament collagen in human and mouse OA,
      respectively. To investigate the relative appearance of pathology in cartilage,
      bone and ligament, we studied the progression of spontaneous OA in the Dunkin
      Hartley (DH) guinea pig knee, and compared with age-matched control Bristol
      Strain 2 (BS2) knees. The classical radiographic OA score of the DH knees
      compared to BS2 knees was 2-fold higher at 24 weeks of age. The patella perimeter
      and subchondral bone density was significantly greater in the DHs at 24 and 36
      weeks compared to BS2. The femoral intercondylar notch width was found to be
      significantly lower in the DHs at 24 and 36 weeks, compared to BS2, indicating
      bone remodelling at the cruciate ligament (CL) insertion site. We found
      significantly greater laxity of the DH anterior CL at 12, 16 and 20 weeks
      compared to BS2. This elevated laxity was associated with increased remodelling
      of the CLs, based on markers of collagen turnover, and occurred prior to bone and
      cartilage pathology. We propose that the laxity of the CL leads to remodelling of
      the subchondral bone, and intercondylar notch, due to a change in load through
      the joint. Remodelling of the CLs and bone occurs prior to and concomitant with
      histopathological changes in the articular cartilage respectively, demonstrating
      the fundamental role of the ligament and subchondral bone in the aetiology of
      knee OA.

PMID- 16912412
TI  - Proceedings of the 4th International Symposium on Mechanobiology of Cartilage and
      Chondrocyte, Budapest, Hungary, 20-22 May 2006.

PMID- 16912413
TI  - Increased apoptosis in rat osteoarthritic cartilage corresponds to degenerative
      chondral lesions and concomitant expression of caspase-3.

PMID- 16912414
TI  - Dynamic compression counteracts IL-1beta induced iNOS and COX-2 activity by human
      chondrocytes cultured in agarose constructs.
AB  - *NO and PGE2 are inflammatory mediators derived from the inducible iNOS and COX
      enzymes and are potentially important pharmacological targets in OA. Both
      mechanical loading and IL-1beta will influence the release of *NO and PGE2.
      Accordingly, the current study examines the effect of dynamic compression on *NO
      and PGE2 release by human chondrocytes cultured in agarose constructs in the
      presence and absence of selective iNOS and COX-2 inhibitors. The current data
      demonstrate that IL-1beta induced nitrite and PGE2 release and inhibited [3H]
      thymidine and 35SO4 incorporation. Inhibitor experiments indicate that 1400W and
      NS-398 either partially reversed or abolished IL-1beta induced nitrite and PGE2
      release. IL-1beta induced inhibition of cell proliferation and proteoglycan
      synthesis was partially reversed with 1400W but was not influenced by NS-398. For
      the dynamic loading experiments, 1400W and NS-398 either reduced or abolished the
      compression-induced inhibition of *NO and PGE2 release in the presence of IL
      1beta. The IL-1beta induced inhibition of cell proliferation was not influenced
      by 1400W or NS-398 whereas strain-induced stimulation of proteoglycan synthesis
      in the presence of IL-1beta was enhanced by 1400W. The data obtained using human
      chondrocytes demonstrate that IL-1beta induced *NO and PGE2 release via an iNOS
      driven-COX-2 inter-dependent pathway. This response could be reversed by dynamic
      compression. These data indicate interactions exist between the NOS and COX
      pathways, a finding which will provide new insights in the development of
      pharmacological or biophysical treatments for cartilage disorders such as OA.

PMID- 16912415
TI  - Treatment of human mesenchymal stem cells with pulsed low intensity ultrasound
      enhances the chondrogenic phenotype in vitro.
AB  - This study examined the effects of low intensity pulsed ultrasound (LIPUS) on
      human bone marrow-derived mesenchymal stem cells undergoing chondrogenic
      differentiation. Aggregates of mesenchymal stem cells and mesenchymal stem cells
      seeded in three dimensional matrices were cultured in a defined chondrogenic
      medium and subjected to LIPUS for the first 7 days of culture. At 1, 7, 14 and 21
      days, samples were harvested for histology, immunohistochemistry, RT-PCR, and
      quantitative DNA and matrix macromolecule analysis. Cell aggregates with daily
      treatment for 20 minutes showed no significant differences for proteoglycan and
      collagen content during chondrogenic differentiation. However ultrasound
      application for 40 minutes daily resulted in a statistically significant increase
      of the proteoglycan and collagen content after 21 days in culture. Aggregates
      treated for 20 minutes daily showed decreased expression of chondrogenic genes at
      all time points. In contrast, 40 minutes of daily treatment of aggregates
      resulted in a significant increase of chondrogenic marker genes after an initial
      decrease at day 7 with time in culture. Ultrasound treated cell-scaffold
      constructs showed a significant increase of chondrogenic marker gene expression
      and extracellular matrix deposition. This study indicates that LIPUS can be used
      to enhance the chondrogenesis of mesenchymal stem cells in cell aggregates and
      cell-scaffold constructs. We have found a dependency on the specific treatment
      parameters. We hypothesize that LIPUS can be used for an improved in vitro
      preparation of optimized tissue engineering implants for cartilage repair.
      Furthermore this non-invasive method could also be of potential use in vivo for
      regenerative therapy of cartilage in the future.

PMID- 16912416
TI  - Mesenchymal progenitor cells in adult human articular cartilage.
AB  - The transmembrane receptor Notch-1 regulates cell fate and differentiation and
      was suggested to identify a cell type with progenitor characteristics in newborn
      bovine articular cartilage. We show that Notch-1 is expressed on > 70% of BM-MSC
      in early passage monolayer culture. We also demonstrate that normal articular
      cartilage contains Notch-1+ cells and that the frequency is increased in OA. Most
      Notch-1+ cells in OA cartilage are located in the clusters of proliferating
      cells. These findings indicate that multipotential mesenchymal progenitor cells
      are present in articular cartilage from adult humans and that their frequency is
      increased in OA. This observation has implications for understanding the
      intrinsic repair capacity of articular cartilage and raises the possibility that
      these progenitor cells might be involved in the pathogenesis of arthritis.

PMID- 16912417
TI  - Dynamic compressive strain influences chondrogenic gene expression in human
      mesenchymal stem cells.
AB  - This study tests the hypothesis that dynamic compressive strain selectively
      enhances chondrogenic differentiation by human mesenchymal stem cells (MSCs).
      Primary MSCs were isolated and expended in monolayer culture. The cells were
      seeded in alginate constructs or in pellet culture. The time course of
      chondrogenic differentiation was assessed by real-time QPCR of mRNA expression
      analysis for cartilage specific markers. Collagen types II and X mRNA, not
      present in undifferentiated MSCs, were detectable by 2-4 days of chondrogenic
      induction and continued to rise significantly throughout the culture period of 10
      days (p < 0.001). Basal levels of gene expression for Sox-9 and aggrecan were
      evident in undifferentiated MSCs, although chondrogenic induction for a period of
      8 days resulted in an increased trend in the gene expression levels. The alginate
      system was also used in mechanical conditioning studies. Dynamic compression was
      applied, in an intermittent regimen, at a strain amplitude of 15% and frequency
      of 1 Hz in the presence and absence of 10 ng/ml TGFbeta3, for a period of 8 days.
      Results indicated significant changes in the levels of mRNA expression for the
      chondrogenic markers. For example, by day 8, the application of the strain
      regimen alone caused an up-regulation in all the chondrogenic markers compared to
      the control samples (no TGFbeta, no compression). However, the combined effects
      of strain and TGFbeta on these markers were more complex than purely additive.

PMID- 16912418
TI  - Human chondrocytes and mesenchymal stem cells grown onto engineered scaffold.
AB  - The development of improved methods for treatment of chondral defects using
      autologous cells in combination with biomaterials leads to a new generation of
      implantable devices. Their association gives rise to a hybrid construct combining
      biological and material components that can be specifically committed. The
      comprehension of cellular and molecular mechanisms of cartilage repair and the
      use of biomaterials in combination with chondrocytes or mesenchymal stem cells in
      the treatment of cartilage defects has opened a new era of therapeutical
      strategies. Recently, their applicability in the treatment of early lesions in
      osteoarthritis is under investigation. To obtain new information on the behaviour
      of chondrocytes and mesenchymal stem cells grown on a hyaluronan derivative
      scaffold (Hyaff-11) already used in cartilage repair, we analysed a series of
      molecules expressed by these cells by Real-Time RT-PCR and immunohistochemical
      analyses. The data obtained with this work showed that this biomaterial is able
      to reduce the expression of some catabolic molecules by human chondrocytes and
      provide a good environment to support the differentiation of mesenchymal stem
      cells in chondrogenic sense. These observations confirm Hyaff-11 as a suitable
      scaffold both for chondrocytes and mesenchymal stem cells for the treatment of
      articular cartilage defects.

PMID- 16912419
TI  - Uniform tissues engineered by seeding and culturing cells in 3D scaffolds under
      perfusion at defined oxygen tensions.
AB  - In this work, we assessed whether culture of uniformly seeded chondrocytes under
      direct perfusion, which supplies the cells with normoxic oxygen levels, can
      maintain a uniform distribution of viable cells throughout porous scaffolds
      several milimeters in thickness, and support the development of uniform tissue
      grafts. An integrated bioreactor system was first developed to streamline the
      steps of perfusion cell seeding of porous scaffolds and perfusion culture of the
      cell-seeded scaffolds. Oxygen tensions in perfused constructs were monitored by
      in-line oxygen sensors incorporated at the construct inlet and outlet. Adult
      human articular chondrocytes were perfusion-seeded into 4.5 mm thick foam
      scaffolds at a rate of 1 mm/s. Cell-seeded foams were then either cultured
      statically in dishes or further cultured under perfusion at a rate of 100
      microm/s for 2 weeks. Following perfusion seeding, viable cells were uniformly
      distributed throughout the foams. Constructs subsequently cultured statically
      were highly heterogeneous, with cells and matrix concentrated at the construct
      periphery. In contrast, constructs cultured under perfusion were highly
      homogeneous, with uniform distributions of cells and matrix. Oxygen tensions of
      the perfused medium were maintained near normoxic levels (inlet congruent with
      20%, outlet > 15%) at all times of culture. We have demonstrated that perfusion
      culture of cells seeded uniformly within porous scaffolds, at a flow rate
      maintaining a homogeneous oxygen supply, supports the development of uniform
      engineering tissue grafts of clinically relevant thicknesses.

PMID- 16912420
TI  - Evaluation of human MSCs cell cycle, viability and differentiation in micromass
      culture.
AB  - Mesenchymal stem cells (MSCs) have the potential to differentiate into distinct
      mesenchymal tissue cells. They are easy to expand while maintaining their
      undifferentiated state, which suggests that these cells could be an attractive
      cell source for tissue engineering of cartilage. In vitro high density micromass
      culture has been widely used for chondrogenesis induction. Our objective was to
      investigate human MSCs cell cycle, viability and differentiation in these
      conditions. Therefore, to induce human MSCs chondrogenesis, micromasses were
      cultured in the presence of transforming growth factor-beta1 in serum free medium
      for 21 days. Cell cycle, cell viability and cell phenotype were analyzed by flow
      cytometry. From day 0 to 7, the G0/G1 phase increased, whereas the S phase
      decreased gradually, but cell cycle phases (S, G0/G1 and G2/M) did not
      significantly change after day 7. Less than 10% of cells were apoptotic, but no
      necrosis was observed, even at day 21. We observed a decrease in CD90 and CD105
      expression, from day 0 to 21. In conclusion, our results demonstrate a good
      viability of human MSCs in micromass culture during the whole period of culture.
      Moreover, micromass culture allowed human MSCs to be synchronized at the G0/G1
      phase, while their phenotype suggested some degree of differentiation.

PMID- 16912421
TI  - Dynamic deformational loading results in selective application of mechanical
      stimulation in a layered, tissue-engineered cartilage construct.
AB  - The application of dynamic physiologic loading to a bilayered chondrocyte-seeded
      agarose construct with a 2% (wt/vol) top layer and 3% (wt/vol) bottom layer was
      hypothesized to (1) improve overall construct properties and (2) result in a
      tissue that mimics the mechanical inhomogeneity of native cartilage. Dynamic
      loading over the 28 day culture period was found to significantly increase bulk
      mechanical and biochemical properties versus free-swelling culture. The initial
      depth-distribution of the compressive Young's modulus (EY) reflected the
      intrinsic properties of the gel in each layer and a similar trend to the native
      tissue, with a softer 2% gel layer and a much stiffer 3% gel layer. After 28 days
      in culture, free-swelling conditions maintained this general trend while loaded
      constructs possessed a reverse profile, with significant increases in EY observed
      only in the 2% gel. Histological analysis revealed preferential matrix formation
      in the 2% agarose layer, with matrix localized more pericellularly in the 3%
      agarose layer. Finite element modeling revealed that, prior to significant matrix
      elaboration, the 2% layer experiences increased mechanical stimuli (fluid flow
      and compressive strain) during loading that may enhance chondrocyte stimulation
      and nutrient transport in that layer, consistent with experimental observations.
      From these results, we conclude that due to the limitations in 3% agarose, the
      use of this type of bilayered construct to construct depth-dependent
      inhomogeneity similar to the native tissue is not likely to be successful under
      long-term culture conditions. Our study underscores the importance of other
      physical properties of the scaffold that may have a greater influence on
      interconnected tissue formation than intrinsic scaffold stiffness.

PMID- 16912422
TI  - Three-dimensional tissue constructs built by bioprinting.
AB  - Bioprinting is an evolving tissue engineering technology. It utilizes computer
      controlled three-dimensional printers for rapid and high-precision construction
      of three-dimensional biological structures. We employed discrete and continuous
      bioprinting to build three-dimensional tissue constructs. In the former case
      bioink particles - spherical cell aggregates composed of many thousands of cells 
      are delivered one by one into biocompatible scaffolds, the biopaper. Structure
      formation takes place by the subsequent fusion of the bioink particles due to
      their liquid-like and self-assembly properties. In the latter case a mixture of
      cells and scaffold material is extruded from the biocartridge akin to toothpaste
      to arrive at the desired construct. Specifically, we built rectangular tissue
      blocks of several hundred microns in thickness as well as tubular structures of
      several millimeters in height. The physical basis of structure formation was
      studied by computer simulations.

PMID- 16912423
TI  - Post-traumatic osteoarthritis: the role of stress induced chondrocyte damage.
AB  - Post-traumatic osteoarthritis is the form of osteoarthritis (OA) that develops
      following joint injury. Although its end-stage is indistinguishable from
      idiopathic OA, many patients with post-traumatic OA are younger than those with
      idiopathic OA, and they have a well-defined precipitating insult. Clinical and
      experimental studies suggest that excessive acute impact energy or chronic
      mechanical overload cause the degeneration of the articular surface responsible
      for post-traumatic OA. Yet, the mechanisms by which excessive mechanical force
      causes OA remain unknown. For these reasons it has not been possible to develop
      effective methods of preventing or decreasing the risk of post-traumatic OA. We
      hypothesized that mechanical loading that exceeds the tolerance of the articular
      surface causes chondrocyte damage due to oxidative stress. Our in vitro tests of
      human articular cartilage samples showed that shear stress causes chondrocyte
      death and that anti-oxidants decrease the shear stress induced cell death. These
      observations suggest that specific patterns of loading are particularly damaging
      to articular surfaces and that improved treatments of joint injuries may include
      mechanical methods of minimizing shear stresses and biologic methods of
      minimizing oxidative damage.

PMID- 16912424
TI  - Acoustic properties of articular cartilage under mechanical stress.
AB  - Mechano-acoustic and elastographic techniques may provide quantitative means for
      the in vivo diagnostics of articular cartilage. These techniques assume that
      sound speed does not change during tissue loading. As articular cartilage shows
      volumetric changes during compression, acoustic properties of cartilage may
      change affecting the validity of mechano-acoustic measurements. In this study, we
      examined the ultrasound propagation through human, bovine and porcine articular
      cartilage during stress-relaxation in unconfined compression. The time of flight
      (TOF) technique with known cartilage thickness (true sound speed) as well as in
      situ calibration method [Suh, Youn, Fu, J. Biomech. 34 (2001), 1347-1353] were
      used for the determination of sound speed. Ultrasound speed and attenuation
      decreased in articular cartilage during ramp compression, but returned towards
      the level of original values during relaxation. Variations in ultrasound speed
      induced an error in strain and compressive moduli provided that constant
      ultrasound speed and time-of-flight data was used to determine the tissue
      thickness. Highest errors in strain (-11.8 +/- 12.0%) and dynamic modulus (15.4
      +/- 17.9%) were recorded in bovine cartilage. TOF and in situ calibration methods
      yielded different results for changes in sound speed during compression. We
      speculate that the variations in acoustic properties in loaded cartilage are
      related to rearrangement of the interstitial matrix, especially to that of
      collagen fibers. In human cartilage the changes, are, however relatively small
      and, according to the numerical simulations, mechano-acoustic techniques that
      assume constant acoustic properties for the cartilage will not be significantly
      impaired by this phenomenon.

PMID- 16912425
TI  - The mechanical environment of chondrocytes in articular cartilage.
AB  - There is a growing literature concerning chondrocyte responses to mechanical
      loading, but relatively little is known about the mechanical environment these
      cells experience in a living joint. Calculations indicate that high forces are
      applied to limb joints whenever the joints are flexed, because flexion can cause
      body weight to act on long lever arms compared to the joint centre, whereas the
      muscles which extend the joint act on much shorter lever arms. As a result, joint
      reaction forces (which compress the cartilage) can rise to 3-6 times body weight
      during activities such as stair climbing. Articular cartilage tends to spread
      this load evenly over the joint surface, but is too thin to do this well, and
      compressive stresses can rise to 10-20 MPa. Within cartilage, matrix stresses
      vary locally, possibly as a result of variation in composition or undulations in
      the subchondral bone, and further modifications of stress occur within each
      chondron. Articular cartilage is a fibrous solid and cells within it are deformed
      by mechanical loading rather than subjected to a hydrostatic pressure. The
      mechanical environment of chondrocytes can best be reproduced in vitro by direct
      compression of the articular surface of cartilage which is supported naturally by
      adjacent cartilage and subchondral bone.

PMID- 16912426
TI  - Age-related quantitative MRI changes in healthy cartilage: preliminary results.
AB  - OBJECTIVES: As the early form of OA is characterized by elevated water content in
      the cartilage tissue, the purpose of this study was to verify in vivo if age
      related changes in patellar cartilage in healthy volunteers can be detected using
      quantitative MRI with T2 mapping and volume measurement MRI methods. DESIGN:
      Thirty healthy volunteers of various classes of age (18 to 65 years old) were
      enrolled in this study. MR images of the patellar cartilage were acquired at
      1.5T. Patellar cartilage volume and T2 maps were determined. RESULTS: Despite non
      significance, there was a trend in reducing cartilage volume with ageing (r: 
      0.25). In contrast global T2 slightly increased with ageing (r: 0.46). BMI (r:
      0.51) and bone volume (r: 0.69) are well correlated to cartilage volume.
      CONCLUSION. Age-related physiologic changes in the water content of patellar
      cartilage can be detected using MRI. The proposed T2-mapping method, coupled with
      other non-invasive MR cartilage imaging techniques, could aid in the early
      diagnosis of OA.

PMID- 16912427
TI  - Bi-zonal cartilaginous tissues engineered in a rotary cell culture system.
AB  - In this study, we aimed at validating a rotary cell culture system (RCCS)
      bioreactor with medium recirculation and external oxygenation, for cartilage
      tissue engineering. Primary bovine and human culture-expanded chondrocytes were
      seeded into non-woven meshes of esterified hyaluronan (HYAFF-11), and the
      resulting constructs were cultured statically or in the RCCS, in the presence of
      insulin and TGFbeta3, for up to 4 weeks. Culture in the RCCS did not induce
      significant differences in the contents of glycosaminoglycans (GAG) and collagen
      deposited, but markedly affected their distribution. In contrast to statically
      grown tissues, engineered cartilage cultured in the RCCS had a bi-zonal
      structure, consisting of an outgrowing fibrous capsule deficient in GAG and rich
      in collagen, and an inner region more positively stained for GAG. Structurally,
      trends were similar using primary bovine or expanded human chondrocytes, although
      the human cells deposited inferior amounts of matrix. The use of the presented
      RCCS, in conjunction with the described medium composition, has the potential to
      generate bi-zonal tissues with features qualitatively resembling the native
      meniscus.

PMID- 16912428
TI  - Effect of peroxisome proliferator activated receptor (PPAR)gamma agonists on
      prostaglandins cascade in joint cells.
AB  - In response to inflammatory cytokines, chondrocytes and synovial fibroblasts
      produce high amounts of prostaglandins (PG) which self-perpetuate locally the
      inflammatory reaction. Prostaglandins act primarily through membrane receptors
      coupled to G proteins but also bind to nuclear Peroxisome Proliferator-Activated
      Receptors (PPARs). Amongst fatty acids, the cyclopentenone metabolite of PGD2, 15
      deoxy-Delta12,14PGJ2 (15d-PGJ2), was shown to be a potent ligand of the PPARgamma
      isotype prone to inhibit the production of inflammatory mediators. As the
      stimulated synthesis of PGE2 originates from the preferential coupling of
      inducible enzymes, cyclooxygenase-2 (COX-2) and membrane PGE synthase-1 (mPGES
      1), we investigated the potency of 15d-PGJ2 to regulate prostaglandins synthesis
      in rat chondrocytes stimulated with interleukin-1beta (IL-1beta). We demonstrated
      that 15d-PGJ2, but not the high-affinity PPARgamma ligand rosiglitazone,
      decreased almost completely PGE2 synthesis and mPGES-1 expression. The inhibitory
      potency of 15d-PGJ2 was unaffected by changes in PPARgamma expression and
      resulted from inhibition of NF-kappaB nuclear binding and IkappaBalpha sparing,
      secondary to reduced phosphorylation of IKKbeta. Consistently with 15d-PGJ2 being
      a putative endogenous regulator of the inflammatory reaction if synthesized in
      sufficient amounts, the present data confirm the variable PPARgamma-dependency of
      its effects in joint cells while underlining possible species and cell types
      specificities.

PMID- 16912429
TI  - Inhibition of interleukin-1beta-induced activation of MEK/ERK pathway and DNA
      binding of NF-kappaB and AP-1: potential mechanism for Diacerein effects in
      osteoarthritis.
AB  - In the present report we have shown that bovine articular chondrocytes cultured
      in low oxygen tension, i.e. in conditions mimicking their hypoxic in vivo
      environment, respond to IL-1beta (10 ng/ml) by an increased DNA binding activity
      of NF-kappaB and AP-l transcription factors. Incubation of the cells with 10(-5)
      M Rhein, the active metabolite of Diacerhein, for 24 h was found to reduce this
      activity particularly in the case of AP-1. Mitogen activated kinases (ERK-1 and
      ERK-2) were activated by exposure of the chondrocytes to a 1 h treatment with IL
      1beta. This effect was greater in hypoxia (3% O2) than in normoxia (21% O2).
      Rhein was capable of reducing the IL-1beta-stimulated ERK1/ERK2 pathway whatever
      the tension of oxygen present in the environment. The mRNA steady-state levels of
      collagen type II (COL2A1) and aggrecan core protein were found to be
      significantly increased by a 24-h treatment with 10(-5) M Rhein. This stimulating
      effect was also observed in the presence of IL-1beta, suggesting that the drug
      could prevent or reduce the IL-1beta-induced inhibition of extra cellular matrix
      synthesis. IL-1-induced collagenase (MMP1) expression was significantly decreased
      by Rhein under the same conditions. In conclusion, Rhein can effectively inhibit
      the IL-1-activated MAPK pathway and the binding of NF-kappaB and AP-1
      transcription factors, two key factors involved in the expression of several pro
      inflammatory genes by chondrocytes. In addition, the drug can reduce the
      procatabolic effect of the cytokine, by reducing the MMP1 synthesis, and enhance
      the synthesis of matrix components, such as type II collagen and aggrecan. These
      results may explain the anti-osteoarthritic properties of Rhein and its disease
      modifying effects on OA cartilage, in spite of the absence of inhibition at
      prostaglandin level.

PMID- 16912430
TI  - Studies in animal models of osteoarthritis as predictors of a structure-modifying
      effect of diacerhein in humans with osteoarthritis.

PMID- 16912431
TI  - IL-1beta synthesis by chondrocyte analyzed by 3D microscopy and flow cytometry:
      effect of Rhein.
AB  - Several factors are known to be involved in the destruction of the articular
      cartilage. Interleukin-1 (IL-1) plays an important role in the pathogenesis of
      osteoarthritis (OA) either directly or through the stimulation of catabolic
      factors. The action of IL-1 on articular cartilage is multifaceted and it most
      likely plays an important role in the mechanism of cartilage destruction. IL-1
      suppresses the synthesis of the cartilage matrix components and promotes the
      degradation of cartilage matrix macromolecules. Diacerein is an anthraquinone
      molecule that has been shown to reduce the severity of OA, both in man and in
      animal models. The present study was designed to evaluate in vitro effects of
      diacerein on IL-1beta expression in LPS or IL-1alpha stimulated chondrocytes.
      Intracellular IL-1beta production was analysed in articular chondrocytes cultured
      in monolayer or in alginate 3D-biosystems in the presence of lipopolysaccharide
      (LPS) or IL-1alpha, with or without diacerein. The results show that LPS and IL
      1alpha increase intracellular IL-1beta and Diacerein inhibited LPS-induced and IL
      1alpha induced IL-1beta production by articular chondrocytes. Moreover, the
      effect of mechanical stimulation was analysed. An inhibitory effect of DAR at
      therapeutic concentrations on IL-1beta production in articular chondrocytes is
      suggested.

PMID- 16912432
TI  - Perspectives on chondrocyte mechanobiology and osteoarthritis.
AB  - Osteoarthritis, the clinical syndrome of joint pain and dysfunction due to joint
      degeneration, is among the most frequent and symptomatic medical problems for
      middle aged and older people, and it is the most common cause of long term
      disability in most populations of people over 65. Currently there are no
      effective methods of preventing or curing osteoarthritis. Post-traumatic OA, the
      joint degeneration, pain and dysfunction that develop following joint injury, is
      the form of OA that is most directly related to elevated articular surface
      contact stress. However, mechanical stress that exceeds the tolerance of the
      articular surface can cause or accelerate the progression of joint degeneration
      in all individuals and in all synovial joints. In some patients, decreasing
      mechanical forces on degenerated joint surfaces stimulates formation of a new
      biologic articular surface. The advances in understanding of the effects of
      mechanical forces on chondrocytes and cartilage presented and discussed at the
      4th Symposium on Mechanobiology: Cartilage and Chondrocyte will help in the
      efforts to develop new methods of preventing and treating osteoarthritis.

PMID- 16912433
TI  - Iron and bacterial virulence.

PMID- 16912434
TI  - Transfusion transmitted leishmaniasis: a case report and review of literature.
AB  - Leishmaniasis is caused by the infection of haemoparasite Leishmania . The
      disease is a major public health problem in at least 88 countries, including
      India. Various species of Leishmania are involved in causing this disease. In
      India, Leishmania donovani species causes visceral leishmaniasis or kala-azar.
      The parasite is mainly transmitted from infected to uninfected person through the
      bites of female sandfly. Rarely the parasite can transmit through placenta from
      mother to child, through sexual intercourse, as laboratory acquired and through
      blood transfusion. This paper reports a unique case of transfusion-transmitted
      fatal kala-azar in an Indian infant who acquired this infection within few days
      of his birth after receiving blood from his maternal uncle, who was asymptomatic
      at the time of blood donation but died due to severe kala-azar within three
      months. The baby started having fever and developed hepatosplenomegaly within one
      month of blood transfusion and in spite of repeated anti-leishmanial treatment
      with sodium antimony gluconate the child died at the age of 7 months. This paper
      details the clinico-pathological findings of this child and also reviews the
      literature on this aspect and its impact on transfusion medicine.

PMID- 16912435
TI  - Antifungal susceptibility testing method for resource constrained laboratories.
AB  - PURPOSE: In resource-constrained laboratories of developing countries
      determination of antifungal susceptibility testing by NCCLS/CLSI method is not
      always feasible. We describe herein a simple yet comparable method for antifungal
      susceptibility testing. METHODS: Reference MICs of 72 fungal isolates including
      two quality control strains were determined by NCCLS/CLSI methods against
      fluconazole, itraconazole, voriconazole, amphotericin B and cancidas.
      Dermatophytes were also tested against terbinafine. Subsequently, on selection of
      optimum conditions, MIC was determined for all the fungal isolates by semisolid
      antifungal agar susceptibility method in Brain heart infusion broth supplemented
      with 0.5% agar (BHIA) without oil overlay and results were compared with those
      obtained by reference NCCLS/CLSI methods. RESULTS: Comparable results were
      obtained by NCCLS/CLSI and semisolid agar susceptibility (SAAS) methods against
      quality control strains. MICs for 72 isolates did not differ by more than one
      dilution for all drugs by SAAS. CONCLUSIONS: SAAS using BHIA without oil overlay
      provides a simple and reproducible method for obtaining MICs against yeast,
      filamentous fungi and dermatophytes in resource-constrained laboratories.

PMID- 16912436
TI  - Molecular epidemiology of clinical isolates of ampc producing Klebsiella
      pneumoniae.
AB  - PURPOSE: AmpC producing K. pneumoniae have been increasingly reported from India
      but epidemiological studies are lacking. In the present study, molecular
      epidemiology of extended-spectrum AmpC beta-lactamases (ESACs) producing clinical
      isolates of K. pneumoniae prevalent in our hospital was studied. METHODS: Fifty
      one non-repeat, consecutive, clinical isolates of K. pneumoniae producing AmpC
      enzymes, were subjected to whole cell protein profile analysis (SDS-PAGE) and
      ribotyping. The antimicrobial susceptibility was determined using standard disk
      diffusion technique. The isolates showing decreased susceptibility to cefoxitin
      (< 18 mm) or cefotetan (< 16 mm) were subjected to modified three- dimensional
      test for detection of AmpC enzyme. RESULTS: Six different types of protein
      profiles were observed. Ribotyping could further discriminate between the strains
      that were clustered by protein fingerprinting. Twelve different ribo-patterns
      were identified. Ribotyping was found to have a better Discriminatory Index
      (0.98) than that of SDS-PAGE (0.78). Of the 26 isolates that showed decreased
      susceptibility to cefoxitin and/or cefotetan 13 isolates were found to harbour
      AmpC enzyme. CONCLUSIONS: The study demonstrated the usefulness of SDS-PAGE whole
      cell protein profile analysis and ribotyping to identify the clonality of the
      ESACs isolates, the latter having a higher discriminatory power. The presence of
      ESACs isolates in the community as well as in hospital settings emphasizes the
      need for regular monitoring of antimicrobial resistance.

PMID- 16912437
TI  - Risk factors and associated problems in the management of infections with
      methicillin resistant Staphylococcus aureus.
AB  - PURPOSE: It is necessary to define the problem of methicillin resistant
      Staphylococcus aureus (MRSA) in every hospital to evolve control strategies. The
      objectives of this study were to determine factors influencing the persistence of
      MRSA in patients with hospital acquired infection and to identify alternate cost
      effective antibiotics. METHODS: A six month study was carried out for 50 patients
      with MRSA infection. Treatment modalities and risk factors were determined by a
      preset protocol. Minimum inhibitory concentration of commonly used antibiotics
      was determined. RESULTS: The risk factors were prolonged postoperative morbidity,
      prior antibiotic therapy and emergency admissions. Seventy percent of the
      isolates were from postoperative cases undergoing emergency surgeries. Isolation
      was highest during the second week of hospital stay. Emergency admissions had a
      significantly higher chance of early isolation. Prior treatment with multiple
      antibiotics in 38% was found to be another major risk factor. Ofloxacin was seen
      to be efficacious in a small percentage of cases. Rifampicin in combination with
      ofloxacin and clindamycin were found to be other good alternatives. Ofloxacin was
      found to be the cheapest and vancomycin the most expensive, for a full course of
      treatment. CONCLUSIONS: Minimizing risk factors and attention to alternate cost
      effective combination therapy may ease the problem of management of infections
      with MRSA.

PMID- 16912438
TI  - DNA fingerprinting elicited evolutionary trend of oral Candida tropicalis
      isolates from diverse geographic locales.
AB  - PURPOSE: To study molecular profiles of oral Candida tropicalis isolates from
      five different geographic locales to determine the molecular diversity, clonality
      and evolutionary trends of this opportunistic pathogen. METHODS: A total of 36
      strains from five countries (China, Canada, Scotland, Japan and Tanzania) were
      genotyped by PCR fingerprinting with 11 separate primers. Of these, primers RSG9,
      RSG8, T3B and RSD12 generated complex fingerprinting patterns. RESULTS: Three
      significantly dissimilar profiles were derived from the primer T3B and
      particularly focused on tDNA suggested the prevalence of genetic subtypes within
      the species. Comparison of tDNA and rDNA (RSD12) fingerprints of C. tropicalis
      suggested that rDNA is much more heterogeneous than the relatively distinct tDNA.
      Further analysis of similarity coefficient (SAB) of gel profiles derived from
      computer-generated dendrograms indicated some degree of similarity in isolates
      from five-disparate geographic locales as well as the presence of unique isotypes
      in each region. CONCLUSIONS: This study demonstrates the evolutionary divergence
      of distinct genetic subgroups within Candida tropicalis .

PMID- 16912439
TI  - Detection of Helicobacter pylori cagA gene in gastric biopsies, clinical isolates
      and faeces.
AB  - PURPOSE: Helicobacter pylori infection is common in the developing countries. The
      cagA gene is a marker of pathogenicity island (PAI) in H. pylori . The aim of
      this study was to determine the prevalence of cagA among dyspeptic patients in
      Bahrain directly from gastric biopsy and stool specimen. METHODS: A total of 100
      gastric biopsy samples, 16 clinical isolates and 44 faecal specimens were
      collected from Bahraini adult dyspeptic patients. cagA gene of H. pylori was
      assessed using polymerase chain reaction (PCR). RESULTS: The cagA gene was
      detected in 59 (59%) from biopsy specimens, 10 (62%) clinical isolates and in 10
      (22.7%) faecal specimens. The detection of cagA positive H. pylori was
      significantly higher in patients with duodenal ulcer (80%) compared to those with
      other endoscopic finding (42%) (P < 0.05). CONCLUSIONS: Using PCR to detect cagA
      gene directly from biopsy is a rapid and reliable technique. However, using stool
      specimen for genotyping in our patients showed reduced sensitivity.

PMID- 16912440
TI  - Simple and economical method for speciation and resistotyping of clinically
      significant coagulase negative staphylococci.
AB  - An attempt was made to speciate 102 clinically significant isolates of coagulase
      negative staphylococci (CoNS) by a practical scheme adapted from various
      references. This scheme utilizes slide and tube coagulase test, urease test
      ornithine decarboxylase, novobiocin susceptibility and aerobic acid from mannose
      for assigning species group. Inclusion of one or two additional tests in a
      species group could identify the isolates to species level. Ninety eight (97%)
      isolates were conveniently identified as S. epidermidis (41%), S. saprophyticus
      (16.6%), S. haemolyticus (14.7%), S. hominis (14.7%), S. lugdunensis (4.9%), S.
      schleiferi (1.9%) and S. capitis (1.9%). Only four isolates were not identified
      to the species level, two of which were probably S. capitis subspecies
      ureolyticus / S. warneri / S. simulans . Antibiotic susceptibility testing showed
      maximum resistance to ampicillin (89%) followed by cefotaxime (59%) with no
      resistance to vancomycin. The increasing recognition of pathogenic potential of
      CoNS and emergence of drug resistance amongst them denotes the need to adopt
      simple laboratory procedures to identify and understand the diversity of
      staphylococci isolated from clinical material.

PMID- 16912441
TI  - SHV-5 extended-spectrum beta-lactamases in clinical isolates of Escherichia coli
      in Malaysia.
AB  - Escherichia coli isolates resistant to ceftazidime isolated in the University
      Malaya Medical Center (UMMC) Kuala Lumpur, Malaysia, between the years 1998 and
      2000 were studied for extended-spectrum beta-lactamase (ESBL) production. All
      strains were analysed phenotypically and genotypically and found to be ESBL
      producing organisms harbouring SHV-5 beta-lactamase. This was confirmed by PCR
      SSCP and nucleotide sequencing of the blaSHV amplified gene. As there was no
      evidence of ESBL activity in E. coli prior to this, coupled with the fact that
      there was a predominance of SHV-5 beta-lactamases in Klebsiella pneumoniae
      isolates in UMMC, we postulate that the E. coli obtained the SHV-5 beta-lactamase
      genes by plasmid transfer from the ESBL-producing K. pneumoniae.

PMID- 16912442
TI  - Occurrence of extended spectrum beta-lactamases among Enterobacteriaceae spp.
      isolated at a tertiary care institute.
AB  - Increasing resistance to third generation cephalosporins has become a cause for
      concern especially among Enterobacteriaceae that cause nosocomial infections. The
      prevalence of extended spectrum beta-lactamases (ESBLs) among members of
      Enterobacteriaceae constitutes a serious threat to current beta-lactam therapy
      leading to treatment failure and consequent escalation of costs. A detailed study
      was initiated to identify the occurrence of ESBLs among the Enterobacteriaceae
      isolates at a tertiary care hospital using the double disk potentiation
      technique. Antibiogram profiles were determined to commonly used antibiotics and
      confirmation of ESBLs production was carried out by the disk diffusion assay
      using ceftazidime and cefotaxime in the presence and absence of clavulanic acid.
      Our results indicate that the majority of ESBLs were expressed in Escherichia
      coli.

PMID- 16912443
TI  - Prevalence of dermatophytes and other fungal agents isolated from clinical
      samples.
AB  - The common cause of skin infections are dermatophytes and opportunistic fungi.
      Aim of this study was to isolate and identify the fungal agents from clinical
      samples from patients with different mycoses. Clinical samples from 165 patients
      were subjected to potassium hydroxide (KOH) examination and culture isolation;
      causative agents were identified macroscopically and microscopically. All the 165
      specimens were KOH positive and 110/165 (66.7%) samples were culture positive. Of
      these, highest isolation rate was obtained in opportunistic mycoses such as
      candidiasis (29/29, 100%). Dermatophytes were isolated in 53/80 (66.3%) specimens
      and Trichophyton rubrum was the commonest isolate in skin samples (17/24) among
      the patients suffering from dermatophytosis. Phaeoannellomyces wernecki was
      isolated in a patient suffering from tinea nigra. The study signifies the
      importance of mycological examination in the diagnosis of various mycoses for
      their effective management.

PMID- 16912444
TI  - Emergence of sporotrichosis in Manipur.
AB  - A retrospective analysis of all cases of sporotrichosis was conducted to examine
      the pattern and frequency of sporotrichosis cases in Manipur over a period of six
      year from July 1999 to June 2005. Seventy-three (73) cases of sporotrichosis were
      detected of which 30 were confirmed by culture and 43 were diagnosed by
      aspiration cytology only. Most of the patients belonged to the age group of 21 to
      40 years (n = 23; 31.5%). There were 39 females (53.4%) and 34 males (46.5%).
      Commonest site of infection was upper limbs (n = 39; 53.4%) followed by lower
      limbs (n = 17; 23.2%). Commonest type of infection was lymphocutaneous form (n =
      46; 63.1%) followed by fixed cutaneous form (n = 27; 36.9%). Among these 73
      cases, 2 male patients (2.7%) were found to be HIV positive. In our experience,
      collection of material by aspiration of pus or infected tissue was found to be a
      better method compared to scraping or exudate. This study revealed Manipur as a
      new endemic area for sporotrichosis.

PMID- 16912445
TI  - Eosinophilic meningitis due to Angiostrongylus cantonensis.
AB  - Angiostrongylus cantonensis is a nematode parasite that inhabits the pulmonary
      arteries and heart of rodents. It is one of the causative agents of fatal
      eosinophilic meningoencephalitis in man. We present five cases of eosinophilic
      meningitis presumably due to infection with Angiostrongylus cantonensis . All the
      five patients gave history of ingestion of monitor lizard within ten days of
      onset of symptoms.

PMID- 16912446
TI  - Pulmonary zygomycosis in a diabetic patient.
AB  - We report a case of pulmonary zygomycosis in an adult male diabetic patient who
      presented with fever and altered sensorium initially and later developed streaky
      haemoptysis. Bronchoscopy showed picture of necrotizing pneumonia. Sputum was
      negative for fungal elements on admission but later bronchial wash and repeat
      sputum samples were positive by microscopy and culture showed growth of Rhizopus
      species. Immediately the patient was put on amphotericin B but had a bout of
      massive haemoptysis and succumbed. A high index of suspicion is needed for an
      early diagnosis and aggressive treatment of this infection in view of the high
      mortality rate.

PMID- 16912447
TI  - Bacteriological techniques compliment the clinical and cytological diagnosis of
      tuberculosis in human immuno deficiency virus infected persons.
AB  - Human immunodeficiency virus (HIV) and M. tuberculosis are two intracellular
      pathogens that interact with each other at both clinical and cellular levels. A
      known HIV positive case, presentingwith vague pulmonary symptoms followed by
      bilateral cervical lymphadenopathy, is reported here. The condition was treated
      as asthma, based on lung symptoms. Cytology revealed acute purulent
      lymphadenitis. Only Z. N. staining and culture of sputum and lymphnode aspirate
      could diagnose tuberculosis. Patient responded well to the standard anti
      tuberculosis treatment.

PMID- 16912448
TI  - Disseminated crytococcosis with extensive cutaneous involvement in AIDS.
AB  - Cutaneous infections is observed in 15% of patients with disseminated
      cryptococcosis with AIDS. We present here a case of a 34 years old female with
      AIDS. She presented with multiple skin coloured umbilicated over face, neck,
      trunk and limbs, which mimicked molluscum contagiosum and kaposi sarcoma. The
      tissue from cutaneous lesions was collected by excision biopsy and processed by
      standard mycological methods. Cryptococcus neoformans was isolated and
      identified. Cerebrospinal fluid (CSF) also yielded the growth of C. neoformans .
      Cryptococcal antigen was detected with a titre of 1024 by Latex agglutination, is
      serum and CSF. Her serum was reactive for HIVI and 2 antibodies. The CD4
      lymphocytes count was 80/cmm. The HIV viral load was 2,48,084 copies/mL. She was
      treated with amphotericin B injectable and oral fluconazole. She responded well
      and lesions regressed.

PMID- 16912449
TI  - Brain abscess due to Scedosporium apiospermum in a non immunocompromised child.
AB  - Scedosporium apiospermum is a filamentous fungi that commonly causes cutaneous
      infection. In certain circumstances, S. apiospermum can also cause invasive
      disease, which can involve the central nervous system (CNS). When the CNS becomes
      involved, treatment is difficult, therapeutic options are limited and the
      prognosis is poor. Early identification and treatment can decrease the mortality
      rate. Here we present a case of brain abscess with chronic suppurative otitis
      media, caused by S. apiospermum. This is the first such case report from Nepal.
      We could identify the organism only post mortem. We could not save the patient,
      probably due to delay in diagnosis.

PMID- 16912450
TI  - Primary orbital aspergilloma of the exenterated orbit in an immunocompromized
      patient.
AB  - Aspergilloma is a fungal ball that usually forms in a preformed stationary
      cavity, mostly in lung and paranasal sinuses. We report a rare case of primary
      orbital Aspergilloma following exenteration for an invasive ocular surface
      squamous neoplasia, clinically mimicking a recurrence of the tumor. The fungal
      ball showed the presence of conidiophores with a globular head and a complete row
      of uni and biserrate phialides, suggestive of Aspergillus flavus species. The
      exposure to air in the orbit, possibly promoted the formation of conidiophores,
      which are normally seen when the organism is located in air cavities.

PMID- 16912451
TI  - Anaerobic bacteraemia in a tertiary care hospital of North India.

PMID- 16912452
TI  - Isolation and methicillin resistance of Staphylococcus aureus from hospital
      personnels.

PMID- 16912453
TI  - Incubation period for culture positivity to detect septicaemia in neonates.

PMID- 16912454
TI  - Culture proven cases of tuberculous meningitis: a 5 year retrospective analysis
      from Vellore.

PMID- 16912455
TI  - [New conceptual framework of GERD - especially regarding pathophysiology of NERD
      and Barrett's esophagus].

PMID- 16912456
TI  - [Genetic abnormality and pancreatitis].

PMID- 16912457
TI  - [Pancreatitis and protease-activated receptor].

PMID- 16912458
TI  - [Pancreatic stellate cells: molecular mechanism of pancreatic fibrosis].

PMID- 16912459
TI  - [A case of granulocyte-colony stimulating factor producing gastric cancer].
AB  - We report a case of granulocyte-colony stimulating factor producing gastric
      cancer with multiple liver metastases. A 68-year-old woman who complained of
      epigastralgia visited our hospital. Upper gastrointestinal endoscopic examination
      revealed a type-2 gastric cancer. The laboratory data at admission indicated
      leukocytosis (35,900/microl) and a high level of serum granulocyte-colony
      stimulating factor (61 pg/mg). Granulocyte-colony stimulating factor producing
      gastric cancer was diagnosed by immunohistochemistry of biopsy specimen. Since we
      detected multiple liver metastases, chemotherapy was performed. Granulocyte
      colony stimulating factor-producing gastric cancer is relatively rare and we
      summarize previous reports.

PMID- 16912460
TI  - [A case of sacroiliitis complicated by ulcerative colitis that was successfully
      treated with steroid].
AB  - A 23-year-old woman was admitted in November, 2002, complaining pain of the left
      side and buttock. She had ulcerative colitis when she was 16 and received medical
      treatment. Based on physical examination and findings of magnetic resonance
      imaging and bone scintigrapy, as sacroiliitis complicated by ulcerative colitis.
      was diagnosed Reports on sacroiliitis and ankylosing spondylitis complicated by
      inflammatory bowel diseases (IBD) are relatively rare in Japan, whereas they are
      common complications of IBD in Western countries. The efficacy of steroids on
      pain relief of sacroiliitis and ankylosing spondylitis is unclear.

PMID- 16912461
TI  - [Successful treatment with oral tacrolimus in a case of severe ulcerative colitis
      complicated with primary diabetes mellitus].
AB  - We report a case of severe ulcerative colitis complicated with primary diabetes
      mellitus that was effectively treated with oral tacrolimus. A 36-year-old man
      suffered his first attack of ulcerative colitis. Because it was difficult to
      control the patient's diabetes, we instituted tacrolimus and azathioprine without
      a corticosteroid regimen as the initial treatment. Within two weeks, the
      ulcerative colitis activity went into remission and the patient's diabetes did
      not worsen.

PMID- 16912462
TI  - [A case of tuberculous lymphadenitis found as an abdominal mass penetrating the
      duodenum].
AB  - A 42-year-old woman who complained of epigastralgia was referred to our hospital
      because of an abdominal mass found by ultrasonography. CT and MRI scans revealed
      that the abdominal mass, 4 cm in diameter, located on the left side of the right
      kidney. Gastroduodenoscopy detected a deep ulcerative lesion covered with a
      yellowish coat in the second portion of duodenum. A sonolucent area at the bottom
      of the ulcerative lesion seemed to expand to the abdominal mass on ultrasonic
      endoscopy. Tuberculosis was one possible differential diagnosis. Pathological
      examination including Ziehl-Neelsen staining using biopsy specimens taken from
      the bottom of the ulcerative lesion did not show tuberculosis infection. However,
      polymerase chain reaction analysis using the biopsy specimens revealed that gene
      expression of tuberculosis was positive. We determined that tuberculous
      lymphadenitis penetrated the duodenum forming an ulcerative lesion in the
      duodenum. The administration of anti-tubercular medicine for 6 months male the
      abdominal mass disappeared and the duodenal ulcerative lesion formed an ulcer
      scar. We report here a case of tuberculous lymphadenitis penetrating the duodenum
      which was successfully treated by conservative therapy without surgical
      treatment.

PMID- 16912463
TI  - [A case of liver cysts with Em18-WB was useful for differential diagnosis].
AB  - A 72-year-old woman with multilocular liver cysts was admitted. This lesions
      seemed to be an alveolar hydatid disease. Two methods of Western blotting were
      used for serologic diagnosis. One method recognizes antigens of crude extracts of
      Echinococcus multilocularis (EM). The other method recognizes a purified antigen
      (Em18) of EM. Her serum only reacted with the former method and never reacted
      with Em18 antigen. Eighteen months after first admission, she had an operation.
      The resected specimen was diagnosed with simple cysts. Western blotting using
      Em18 antigen could greatly facilitate the differential diagnosis of simple liver
      cyst and alveolar hydatid disease.

PMID- 16912464
TI  - [Clinical course of 4 cases of hepatic peribiliary cysts and a summary of the 38
      clinical cases reported in Japan].
AB  - We encountered 4 cases of hepatic peribiliary cysts (HPBC) in our hospital. Two
      were asymptomatic, one was complicated by a choledocholithiasis, and one by
      cholangitis and sepsis. Based on a review of the 38 cases of HPBC clinically
      diagnosed in Japan, the main problem associated with this disease seemed
      incorrect preoperative diagnosis leading to an unnecessary hepatectomy. Another
      problem was concomitant cholangitis, which tended to recur and in some cases
      needed aggressive treatment using drainage.

PMID- 16912465
TI  - Evolution of neurotrophic factors: preface with a historical perspective.

PMID- 16912466
TI  - Evolution of the neurotrophin signaling system in invertebrates.
AB  - Nucleotide sequences encoding orthologs of neurotrophins and their receptors,
      p75(NTR) and Trk receptors, have been identified in the sea urchin
      Strongylocentrotus purpuratus, and the acorn worm, Saccoglossus kowalevskii,
      whereas the ascidian (sea squirt) species Ciona intestinalis and Ciona savignii
      appear to lack such orthologs. These results suggest that a functional
      neurotrophin system was already present at the beginning of deuterostome
      evolution, but was lost in ascidians. Remarkably, it appears that evolution of a
      p75(NTR) ortholog represented one of the earliest events in the expansion of the
      tumor necrosis factor receptor superfamily.

PMID- 16912467
TI  - Formation and evolution of the chordate neurotrophin and Trk receptor genes.
AB  - Neurotrophins are structurally related neurotrophic polypeptide factors that
      regulate neuronal differentiation and are essential for neuronal survival,
      neurite growth and plasticity. It has until very recently been thought that the
      neurotrophin system appeared with the vertebrate species, but identification of a
      cephalochordate neurotrophin receptor (Trk), and more recently neurotrophin
      sequences in several genomes of deuterostome invertebrates, show that the system
      already existed at the stem of the deuterostome group. Comparative genomics
      supports the hypothesis that two whole genome duplications produced many of the
      vertebrate gene families, among those the neurotrophin and Trk families. It
      remains to be proven to what extent the whole genome duplications have driven
      macroevolutionary change, but it appears certain that the formation of the multi
      gene copy neurotrophin and Trk receptor families at the stem of vertebrates has
      provided a foundation from which the various functions and pleiotropic effects
      produced by each of the four extant neurotrophins have evolved.

PMID- 16912468
TI  - Tracing the evolution and function of the Trk superfamily of receptor tyrosine
      kinases.
AB  - Most growth factors and their receptors have been strongly conserved during
      evolution. In contrast, Trks (Tropomyosin-related kinases) and related receptors
      in the Trk superfamily, Rors (receptor tyrosine kinase-like orphan receptors),
      Musks (muscle specific kinases) and Ddrs (discoidin domain receptor family),
      appear to be ancient, but their function has been lost in multiple lineages and
      the roles for the receptors have been modified over time. We will trace the
      evolution of the Trk superfamily and discuss possible conserved functional roles,
      including a unifying theme of target recognition by growing axons. We present an
      analogy between the evolution of G-protein-coupled receptors and receptor
      tyrosine kinases (RTKs), proposing that an important driving force for the
      divergence of receptors is the ease of divergence of their ligands.

PMID- 16912469
TI  - Comparative analysis of neurotrophin receptors and ligands in vertebrate neurons:
      tools for evolutionary stability or changes in neural circuits?
AB  - To better understand the role of multiple neurotrophin ligands and their
      receptors in vertebrate brain evolution, we examined the distribution of trk
      neurotrophin receptors in representatives of several vertebrate classes. Trk
      receptors are largely expressed in homologous neuronal populations among
      different species/classes of vertebrates. In many neurons, trkB and trkC
      receptors are co-expressed. TrkB and trkC receptors are primarily found in
      neurons with more restricted, specialized dendritic and axonal fields that are
      thought to be involved in discriminative or 'analytical' functions. The
      neurotrophin receptor trkA is expressed predominantly in neurons with larger,
      overlapping dendritic fields with more heterogeneous connections ('integrative'
      or 'modulatory' systems) such as nociceptive and sympathetic autonomic nervous
      system, locus coeruleus and cholinergic basal forebrain. Surveys of trk receptor
      expression and function in the peripheral nervous system of different vertebrate
      classes reveal trends ranging from dependency on a single neurotrophin to a more
      complex dependency on increasing numbers of neurotrophins and their receptors,
      for example, in taste and inner ear innervation. Gene deletion studies in mice
      provide evidence for a complex regulation of neuronal survival of sensory
      ganglion cells by different neurotrophins. Although expression of neurotrophins
      and their receptors is predominantly conserved in most circuits, increasing
      diversity of neurotrophin ligands and their receptors and a more complex
      dependency of neurons on neurotrophins might have facilitated the formation of at
      least some new neuronal entities.

PMID- 16912470
TI  - Neurotrophic and gliatrophic contexts in Drosophila.
AB  - Trophic interactions in the vertebrate nervous system enable the adjustment of
      cell number and axon guidance, targeting and connectivity. Computational analysis
      of the sequenced Drosophila genome failed to identify some of the main trophic
      factors, the neuregulins and neurotrophins, as well as many other genes. This
      provoked speculations that the Drosophila nervous system might not require such
      regulative interactions. Here we review abundant cellular, genetic and functional
      data that demonstrate the existence of both neurotrophic and gliatrophic
      interactions in the Drosophila nervous system. Glial survival is maintained by
      the epidermal growth factor receptor (EGFR) signaling pathway in response to the
      ligands Spitz, a transforming growth factor-alpha (TGF-alpha) signaling molecule,
      and Vein, a neuregulin homologue. Cellular and genetic evidence predicts the
      existence of neuronal trophic factors operating at least in the Drosophila embryo
      during axon guidance and, in the visual system, during the targeting of retinal
      axons in the brain.

PMID- 16912471
TI  - Evolution of the GDNF family ligands and receptors.
AB  - Four different ligand-receptor binding pairs of the GDNF (glial cell line-derived
      neurotrophic factor) family exist in mammals, and they all signal via the
      transmembrane RET receptor tyrosine kinase. In addition, GRAL (GDNF Receptor
      Alpha-Like) protein of unknown function and Gas1 (growth arrest specific 1) have
      GDNF family receptor (GFR)-like domains. Orthologs of the four GFRalpha
      receptors, GRAL and Gas1 are present in all vertebrate classes. In contrast,
      although bony fishes have orthologs of all four GDNF family ligands (GFLs), one
      of the ligands, neurturin, is absent in clawed frog and another, persephin, is
      absent in the chicken genome. Frog GFRalpha2 has selectively evolved possibly to
      accommodate GDNF as a ligand. The key role of GDNF and its receptor GFRalpha1 in
      enteric nervous system development is conserved from zebrafish to humans. The
      role of neurturin, signaling via GFRalpha2, for parasympathetic neuron
      development is conserved between chicken and mice. The role of artemin and
      persephin that signal via GFRalpha3 and GFRalpha4, respectively, is unknown in
      non-mammals. The presence of RET- and GFR-like genes in insects suggests that a
      ProtoGFR and a ProtoRET arose early in the evolution of bilaterian animals, but
      when the ProtoGFL diverged from existing transforming growth factor (TGFbeta)
      like proteins remains unclear. The four GFLs and GFRalphas were presumably
      generated by genome duplications at the origin of vertebrates. Loss of neurturin
      in frog and persephin in chicken suggests functional redundancy in early
      tetrapods. Functions of non-mammalian GFLs and prechordate RET and GFR-like
      proteins remain to be explored.

PMID- 16912472
TI  - Building complex brains--missing pieces in an evolutionary puzzle.
AB  - The mechanisms underlying evolution of complex nervous systems are not well
      understood. In recent years there have been a number of attempts to correlate
      specific gene families or evolutionary processes with increased brain complexity
      in the vertebrate lineage. Candidates for evocation of complexity include genes
      involved in regulating brain size, such as neurotrophic factors or microcephaly
      related genes; or wider evolutionary processes, such as accelerated evolution of
      brain-expressed genes or enhanced RNA splicing or editing events in primates. An
      inherent weakness of these studies is that they are correlative by nature, and
      almost exclusively focused on the mammalian and specifically the primate lineage.
      Another problem with genomic analyses is that it is difficult to identify
      functionally similar yet non-homologous molecules such as different families of
      cysteine-rich neurotrophic factors in different phyla. As long as comprehensive
      experimental studies of these questions are not feasible, additional perspectives
      for evolutionary and genomic studies will be very helpful. Cephalopod mollusks
      represent the most complex nervous systems outside the vertebrate lineage, thus
      we suggest that genome sequencing of different mollusk models will provide useful
      insights into the evolution of complex brains.

PMID- 16912474
TI  - Somatosensory areas of manatee cerebral cortex: histochemical characterization
      and functional implications.
AB  - A histochemical and cytoarchitectural analysis was completed for the neocortex of
      the Florida manatee in order to localize primary sensory areas and particularly
      primary somatosensory cortex (SI). Based on the location of cytochrome oxidase
      dense staining in flattened cortex preparations, preliminary functional divisions
      were assigned for SI with the face represented laterally followed by the flipper,
      body and tail representations proceeding medially. The neonate exhibited four
      distinct patches in the frontoparietal cortex (presumptive SI), whereas juvenile
      and adult specimens demonstrated a distinct pattern in which cytochrome oxidase
      dense staining appeared to be blended into one large patch extending
      dorsomedially. This differential staining between younger versus older more
      developed animals was also seen on coronal sections stained for cytochrome
      oxidase, myelin, or Nissl bodies. These were systematically analyzed in order to
      accurately localize the laminar and cytoarchitectural extent of cytochrome
      oxidase staining. Overall, SI appears to span seven cytoarchitectural areas to
      which we have assigned presumptive functional representations based on the
      relative locations of cytochrome oxidase-dense staining.

PMID- 16912473
TI  - Plasticity of auditory medullary-midbrain connectivity across metamorphic
      development in the bullfrog, Rana catesbeiana.
AB  - On the basis of patterns of anterograde, retrograde, and bi-directional transport
      of tracers from both the superior olivary nucleus (SON) and the torus
      semicircularis (TS), we report anatomical changes in brainstem connectivity
      across metamorphic development in the bullfrog, Rana catesbeiana. In early and
      late stages of larval development (Gosner stages 25-37), anterograde or bi
      directional tracers injected into the SON produce terminal/fiber label in the
      contralateral SON and in the ipsilateral TS. Between stages 38-41 (deaf period),
      only sparse or no terminal/fiber label is visible in these target nuclei. During
      metamorphic climax (stages 42-46), terminal/fiber label reappears in both the
      contralateral SON and in the ipsilateral TS, and now also in the contralateral
      TS. Injections of retrograde tracers into the SON fail to label cell bodies in
      the ipsilateral TS in deaf period animals, mirroring the previously-reported
      failure of retrograde transport from the TS to the ipsilateral SON during this
      developmental time. Bilateral cell body label emerges in the dorsal medullary
      nucleus and the lateral vestibular nucleus bilaterally as a result of SON
      transport during the late larval period, while cell body label in the
      contralateral TS emerges during climax. At all larval stages, injections into the
      SON produce anterograde and retrograde label in the medial vestibular nucleus
      bilaterally. These data show anatomical stability in some pathways and plasticity
      in others during larval development, with the most dramatic changes occurring
      during the deaf period and metamorphic climax. Animals in metamorphic climax show
      patterns of connectivity similar to that of froglets and adults, indicating the
      maturation during climax of central anatomical substrates for hearing in air.

PMID- 16912475
TI  - Determinants of carotid plaque occurrence. A long-term prospective population
      study: the San Daniele Project.
AB  - BACKGROUND: Increased carotid intima media thickness (CIMT) is frequently
      associated with established modifiable and non-modifiable cardiovascular risk
      factors, and is thought to be an independent predictor of ischemic
      cerebrovascular and cardiac events. The presence of carotid plaque is considered
      an established feature of atherosclerosis. There exist few longitudinal data on
      the predictive role of CIMT in the occurrence of carotid plaque. METHODS: We
      restudied the survivors of a cohort of the San Daniele Project, a large
      randomized general population study, investigated in 1990 regarding the
      prevalence and determinants of carotid atherosclerosis. Using ultrasonography, we
      determined in 1,193 subjects (548 men and 645 women), the common carotid IMT and
      the presence of non-stenotic and stenotic plaque. RESULTS: In 795 subjects
      without plaques or previous ischemic events at baseline, we found in multivariate
      analysis that CIMT > or =1 mm, age, hypertension and history of smoking are
      significant predictive elements of the occurrence of a new carotid plaque. The
      incremental probability of plaque occurrence is greater in midlife. CIMT and age
      are the most predictive risk factors with ORs of 3.66 (95% CI 1.4-9.4) and 3.02
      (95% CI 2.4-3.7), respectively. The ORs for hypertension and smoking account for
      1.5 (95% CI 1.1-3.4) and 1.7 (95% CI 1.1-2.8), respectively. CONCLUSIONS: Age,
      hypertension, history of smoking and B-mode detection of CIMT increases in
      subjects without carotid atherosclerosis and free of previous vascular events
      predict the occurrence of carotid atherosclerotic plaque.

PMID- 16912476
TI  - Eligibility for recombinant tissue plasminogen activator in acute ischemic
      stroke: way to endeavor.
AB  - BACKGROUND: The eligibility for recombinant tissue plasminogen activator (rtPA)
      is rare. We analyze the reasons for exclusion from rtPA among patients who were
      admitted to our hospital within 3 h. METHODS: A strict protocol for hyperacute
      stroke was set in a university teaching hospital. Consecutive patients activating
      the protocol from June 2004 to October 2005 were prospectively registered and
      entered into a computerized database. The patients were excluded from rtPA
      according to the modified exclusion criteria from the National Institute of
      Neurological Disorders and Stroke rtPA trial. RESULTS: Of the 182 patients
      activating the protocol, only 11 (6.04%) received intravenous rtPA and 4 (2.2%)
      IA thrombolysis. Patients were excluded for multiple reasons, and the main
      reasons for exclusion were minor or improving stroke (46.15%), hypertension
      (35.16%), insufficient time to complete studies or onset beyond 3 h after
      reconfirmation (24.17%) and intracranial hemorrhage (15.93%). Of 167 excluded
      patients, 72 (43.11%) were excluded by a single criterion, 53 (31.73%) by 2
      criteria and 29 (17.36%) by 3 criteria. The mean time from hospital arrival to
      presentation to a neurologist was 9.24 +/- 15.11 min (n = 164, median = 8.00,
      mode = 10, range = 0-65). The mean time from hospital arrival to computed
      tomography (CT) was 21.67 +/- 23.95 min (n = 167, median = 20.00, mode = 10,
      range = 4-68). CONCLUSION: An intrahospital stroke code was implemented to
      minimize intrahospital delay. However, only 11 patients received intravenous rtPA
      and 4 IA thrombolysis at our hospital from June 2004 to October 2005. The result
      brings into question the neurologist's conservative interpretation of the
      criteria and the necessity to clearly define some criteria. Furthermore an
      intrahospital stroke code should also be implemented for inpatients to maximize
      the eligibility for rtPA.

PMID- 16912477
TI  - Intravenous thrombolysis in German stroke units before and after regulatory
      approval of recombinant tissue plasminogen activator.
AB  - BACKGROUND: Intravenous thrombolysis with recombinant tissue plasminogen
      activator (rt-PA) within 3 h after onset of focal cerebral ischemia was approved
      in Germany in August 2000. METHODS: 11 neurology departments with acute stroke
      units participated in the German Stroke Study Collaboration before (n = 2,925)
      and after (n = 3,204) approval of rt-PA in Germany and consecutively registered
      all patients admitted within 24 h following acute ischemic stroke. RESULTS:
      Frequency of intravenous thrombolysis in patients admitted within 24 h after
      symptom onset increased from 4.8% before approval to 7.9% after approval of rt
      PA. Among patients treated with rtPA, age increased significantly and the delay
      between symptom onset and imaging was significantly shorter in the second study
      period. CONCLUSIONS: The observed improvement in management and quantity of
      intravenous thrombolysis may be explained by greater experience and greater legal
      security following regulatory approval of rtPA.

PMID- 16912478
TI  - Serial measurements of N-terminal pro-brain natriuretic peptide after acute
      ischemic stroke.
AB  - BACKGROUND: The exact time-course of N-terminal pro-brain natriuretic peptide (NT
      proBNP) and the prognostic importance in the immediate phase of ischemic stroke
      have not been established. METHODS: NT-proBNP was measured daily from admission
      to day 5 and again at 6-month follow-up in 250 consecutive patients with acute
      ischemic stroke. RESULTS: NT-proBNP peaked the day after onset of symptoms (p =
      0.007) followed by a decrease until day 5 (p = 0.001, ANOVA). At 6-month follow
      up the difference in the level of NT-proBNP was unchanged compared to day 5 (p =
      0.42). NT-proBNP levels > or =615 pg/ml at day 2 after onset of symptoms was
      associated with 6-month mortality. CONCLUSION: NT-proBNP peaks the day after
      onset of symptoms in patients with acute ischemic stroke. A single measurement of
      NT-proBNP appears to be an indicator of 6-month mortality.

PMID- 16912479
TI  - Regional quantification of white matter hyperintensity in normal aging, mild
      cognitive impairment, and Alzheimer's disease.
AB  - BACKGROUND/AIMS: A quantitative method was applied to measure the volume of white
      matter hyperintensity (WMH) in different brain regions of subjects with
      Alzheimer's disease (AD), mild cognitive impairment (MCI) and normal healthy age
      matched controls, and the relationship between regional WMH and age and cognitive
      function was investigated. METHODS: Fifty-six subjects were included in this
      study, 27 AD, 15 MCI and 14 normal age-matched controls. A user-friendly software
      was developed for WMH quantification in frontal, temporal, and parieto-occipital
      lobes. Mini-Mental State Examination and cognitive scores in performing naming,
      language fluency, and memory tasks were obtained for correlation analysis.
      RESULTS: AD patients had the greatest total WMH volume, followed by MCI, then
      controls. However, there was a large variation within each group, and the
      difference did not reach a significant level. There was a positive linear
      correlation between the total WMH (p = 0.031) and the frontal WMH (p = 0.006) vs.
      age. After age correction the Boston Naming Test scores were negatively
      correlated with the total WMH volume in the AD (p = 0.03) and the control (p =
      0.03) groups, and with the frontal WMH in controls (p = 0.01). CONCLUSION: We
      demonstrated a quantitative analysis method to measure regional WMH. Although WMH
      was not strongly associated with disease severity or cognition, it may provide a
      characteristic neuroimaging parameter in the study of AD development.

PMID- 16912480
TI  - Effects of high-frequency cranial electrostimulation on the rest-activity rhythm
      and salivary cortisol in Alzheimer's disease: a pilot study.
AB  - OBJECTIVE: In a previous study, low-frequency (0.5 Hz) cranial electrostimulation
      (CES) neither improved the rest-activity rhythm nor reduced the level of salivary
      cortisol in patients with probable Alzheimer's disease (AD). To investigate
      whether the frequency of CES was responsible for these negative findings, we set
      out to examine the effects of high-frequency CES on the rest-activity rhythm and
      salivary cortisol of patients with probable AD. We hypothesized that a decreased
      level of cortisol would parallel a positive effect of high-frequency CES on
      nocturnal restlessness in AD patients. METHODS: Twenty AD patients were randomly
      assigned to an experimental group (n = 10) and a control group (n = 10). The
      experimental group was treated with high-frequency CES, the control group
      received sham stimulation, for 30 min a day, during 6 weeks. The rest-activity
      rhythm was assessed by actigraphy. Level of cortisol was measured by means of
      salivette tubes. RESULTS: The rest-activity rhythm and the level of salivary
      cortisol did not react positively to high-frequency CES. In contrast, both groups
      showed an increase in the level of cortisol after the 6-week treatment period.
      CONCLUSIONS: High-frequency CES appeared to be ineffective in AD patients.

PMID- 16912481
TI  - Role of glyceryl trinitrate, a nitric oxide donor, in the renal ischemia
      reperfusion injury of rats.
AB  - BACKGROUND/AIMS: Ischemia-reperfusion injury is a serious clinical situation
      which can cause serious morbidity and mortality. An experimental renal ischemia
      reperfusion injury model was designed to evaluate the role of glyceryl trinitrate
      (GTN) on renal function and histology. METHODS: 50 Wistar albino rats were used
      in our study. Five groups were formed: (1) sham-control group; (2) acute renal
      ischemia (ARI) group with placebo (0.9% NaCl) infusion; (3) GTN infusion with a
      75 microg/kg/min dose prior to ARI was administered; (4) GTN infusion with a 150
      microg/kg/min dose prior to ARI was given, and finally (5) 150 microg/kg/min GTN
      infusion after the ARI period was applied. Serum BUN and creatinine levels were
      measured for evaluation of renal function. T(max-sec), glomerular filtration rate
      (GFR), and T(max-min) results following a (99m)Tc-DTPA diuretic renal
      scintigraphy were used. Histological examination was performed on nephrectomy
      specimens. RESULTS: Groups 2 and 5 showed higher BUN, creatinine, and lower GFR
      values than the other groups (p = 0.0001). There was no difference in BUN,
      creatinine, and GFR levels between groups 2 and 5 (p = 0.971, p = 0.739, p =
      0.393). Also the T(max-sec) values were higher in groups 2 and 5 compared with
      the other groups (p = 0.0001). The presence of tubular necrosis was different
      between groups and was higher in groups 2 and 5 (p = 0.002). CONCLUSION: The
      application of GTN, a nitric oxide donor, has caused significant improvement in
      renal function when applied prior to an experimentally designed renal ischemia
      reperfusion model. But administration of GTN had no effect after occurrence of
      ischemia.

PMID- 16912482
TI  - Detection of lymphatic invasion in early stage primary colorectal cancer with the
      monoclonal antibody D2-40.
AB  - PURPOSE: The purpose of this study was to investigate the presence of lymphatic
      invasion detected by D2-40 immunostaining compared to conventional hematoxylin
      eosin (HE) staining in primary colorectal cancer (CRC) and the development of
      focal new lymphangiogenesis and peritumoral lymphatic proliferation in relation
      to the tumor stages. Additionally, we analyzed the relation of peritumoral
      inflammatory reaction (PIR) to tumor stages in CRC. The identification of new
      categories of patients with high-risk CRC would be very helpful in improving
      treatment strategies and patient outcome especially in early CRC. PATIENTS AND
      METHOD: Biopsies were taken from 41 patients with colorectal adenocarcinomas at
      different stages of disease. Immunohistochemistry was performed on paraffin
      embedded sections. First, the whole section was screened for the presence of
      lymphatic invasion and PIR with routine HE staining. After analysis of the HE
      stained slides, the slides were destained and reused for immunohistochemistry
      with the D2-40 monoclonal antibody. D2-40-immunostained sections were screened
      for the presence of lymphatic invasion, the proliferation of lymphatic vessels
      and focally newly developed lymph vessels. RESULTS: Using the D2-40 antibody for
      immunostaining, our results demonstrate a significantly higher detection (p <
      0.05) of lymphatic vessel invasion compared to routine HE staining in primary
      CRC. 22% more patients with lymphatic vessel invasion could be identified
      compared to routine HE staining, especially in node-negative tumor stage (UICC
      II). The positive predictive value of lymphatic invasion evaluated by D2-40
      immunostaining to predict lymph node metastasis is 92% (negative predictive value
      81%). High PIR was shown in UICC stage I and II. These infiltrations were rarely
      seen in UICC stage III and were absent in UICC stage IV. Higher UICC tumor stage
      is associated with a higher rate of focally newly developed lymphatic vessels. In
      UICC stage I we found peritumoral lymphatic vessel proliferation only in one case
      (14%) and in UICC stage II no case was found. 47% of the cases in UICC stage III
      and 50% of the cases in UICC stage IV showed focal peritumoral lymphatic vessel
      proliferation. CONCLUSIONS: Immunostaining with D2-40 significantly increased the
      detection rate of lymphatic invasion compared to conventional HE staining in
      primary CRC. The D2-40 antibody specific for lymphatic endothelium cells has the
      potential for a prognostic marker in early stage CRC. Further prospective studies
      are necessary to evaluate the prognostic value of lymphatic invasion and the
      induction of tumor lymphangiogenesis and its role in human cancer progression.

PMID- 16912484
TI  - Effect of a selective cyclooxygenase-2 inhibitor on renal scarring.
AB  - BACKGROUND: Scarring is one of the steps of excessive wound healing, causing
      dysfunction of the involved tissues and clinically poor cosmetics. The aim of
      this study was to examine the effect of a highly selective cyclooxygenase-2 (COX
      2) inhibitor on renal scar formation in experimental pyelonephritis. MATERIALS
      AND METHODS: Four groups of 10 Balb/C mice were formed. In groups I and II
      following the inoculation of lipopolysaccharide (LPS) into both kidneys, 0.18 and
      0.36 mg/day of rofecoxib was given respectively via intraperitoneal route for 5
      days. No medication was applied following physiological saline solution injection
      to both kidneys of the mice in group III (negative control group). After group
      IV's LPS inoculation on the first day, saline solution (1 ml/day) was given
      intraperitoneally for 5 days (positive control group). Following the exposure of
      both kidneys, LPS of Escherichia coli (5 mg/kg) was injected into the kidneys of
      groups I, II, and IV. In group III, saline solution (0.1 ml) was used instead of
      LPS. Three days after the inoculation of LPS, solutions containing 0.18 and 0.36
      mg of COX-2 inhibitor were given intraperitoneally for 5 days in groups I and II.
      No medication was used for the mice in group III. Six weeks after the inoculation
      of LPS and saline solution, all mice were humanely euthanized. Bilateral
      nephrectomies were done on each group of mice, and histopathological examination
      was performed. RESULTS: Inoculation of LPS into the renal parenchyma caused
      pyelonephritis and scar formation in all groups. The degree of pyelonephritis and
      scar formation was lesser in groups in which COX-2 inhibitors were used. The
      degree of scar formation was lesser in group II, in which 0.36 mg more of COX-2
      inhibitor was used than in group I (0.18 mg of COX-2 inhibitor). CONCLUSION: In
      our study model, direct inoculation of LPS to kidneys caused experimentally
      induced pyelonephritis. Renal scar formation was effectively prevented through
      the utilization of rofecoxib at 0.36-mg doses.

PMID- 16912483
TI  - Protective effects of ulinastatin on proliferation and cytokine release of
      splenocytes from rats with severe acute pancreatitis.
AB  - AIM: To clarify the contributions of ulinastatin to cellular immune responses in
      vivo, we examined the functional alterations of splenocytes and quantitatively
      evaluated the effects of ulinastatin on the splenocyte function during
      experimental severe acute pancreatitis. METHODS: Severe acute pancreatitis was
      induced in rats by retrograde injection of 3% sodium deoxycholate. Thirty minutes
      after induction of pancreatitis, the rats were randomly assigned to four groups,
      receiving either saline or 50,000 U/kg of ulinastatin, respectively. Splenocytes
      were obtained aseptically and stimulated with concanavalin A for 24 h. Then the
      proliferative activity of cultured splenocytes was measured by using an MTT
      cellular proliferation assay, and the cytokine concentrations in the culture
      supernatants were measured by enzyme-linked immunosorbent assays. RESULTS: Upon
      stimulation, the release of interleukin-2, interleukin-10, and interferon-gamma
      was significantly decreased in the splenocytes from rats with pancreatitis as
      compared with those from sham operation and control groups. The splenocyte
      proliferation was also significantly suppressed in this group. In contrast, the
      proliferative as well as the cytokine-releasing capacities of the splenocytes
      from rats treated with ulinastatin were significantly increased as compared with
      those from rats with pancreatitis. CONCLUSIONS: The deficiencies in proliferation
      and cytokine release in response to antigen stimulation demonstrated an anergic
      state of splenocytes during severe acute pancreatitis. Treatment with ulinastatin
      contributed to the recovery of the immune function by improving proliferative
      responses and cytokine release of splenocytes. These data suggest that a protease
      modulating therapy may be an effective strategy for the treatment of
      immunosuppression induced by severe acute pancreatitis.

PMID- 16912485
TI  - Efficiency of 4% icodextrin in preventing adhesions to spiral tacks used to fix
      intraperitoneal prostheses.
AB  - BACKGROUND/AIMS: This study was designed to evaluate the extent of adhesion
      formation to prostheses fixed with spiral tacks and to establish whether the use
      of Ringer's lactate or icodextrin could prevent these adhesions. METHODS: 24 New
      Zealand white rabbits weighing around 3,000 g were implanted with a 7 x 5 cm
      patch of ePTFE (DualMesh) through a midline laparotomy. The prosthesis was fixed
      to the intact peritoneum using spiral tacks. Three study groups were established
      according to whether the animals were: implanted with ePTFE fixed with spiral
      tacks or implanted with ePTFE fixed with spiral tacks and simultaneously
      administered Ringer's lactate or 4% icodextrin in the peritoneal cavity. Adhesion
      formation and prosthetic behavior at the prosthesis/peritoneal interface were
      evaluated and quantified by sequential laparoscopy performed at 3, 7 and 14 days.
      RESULTS: Adhesions generally formed on the tacks and were classified as the fully
      integrated type. No significant differences were observed in terms of the extent
      of adhesions or of neoperitoneal thickness between control animals and those
      receiving Ringer's lactate or icodextrin. CONCLUSIONS: (a) Prosthesis-fixing
      tacks induced adhesions; (b) the use of substances such as icodextrin or Ringer's
      lactate does not seem to diminish adhesion formation, and (c) the use of
      icodextrin offered no benefits over that of Ringer's lactate solution.

PMID- 16912486
TI  - Short-rib-polydactyly syndrome presenting with increased nuchal translucency in a
      high-risk family.
AB  - Short-rib-polydactyly syndrome represents a group of rare, autosomal recessive,
      lethal skeletal dysplasias characterized by hypoplastic thorax, short ribs, short
      limbs, polydactyly, and visceral abnormalities. We describe an affected fetus
      from a high-risk family presenting with increased nuchal translucency at 13 weeks
      of pregnancy. The diagnosis was established in the 2nd trimester.

PMID- 16912487
TI  - Non-invasive detection of fetal rhesus D status: a comparison between polymerase
      chain reaction and flow cytometry.
AB  - OBJECTIVE: A non-invasive prenatal determination of the fetal RhD status might be
      useful for the management of pregnancies in RhD-negative women whose partners are
      RhD positive. METHODS: Maternal peripheral blood of 32 RhD-negative women (17-24
      weeks of gestation) was collected, and circulating fetal cells were enriched by
      CD71 mini-magnetic activated cell sorting. The RhD status of the fetuses was
      assessed using multiparametric flow cytometry, and results were compared to those
      of reverse transcriptase (RT)-polymerase chain reaction (PCR), or PCR, which
      acted as control. Flow-cytometric study of fetal cells employed monoclonal
      antibodies directed against CD71, glycophorin A (GPA) and RhD antigens. RESULTS:
      The median percentage of CD71- and RhD-positive cells was 0.83% (range 0.14
      6.44%), and that of CD71 and GPA-positive cells was 10.07% (range 0.52-45.84%).
      Flow-cytometric analysis correlated with RT-PCR results of RNA obtained from
      whole maternal blood. In 1 case, an incorrect result was due to the failure of
      the amplification of the specific RhD band on RNA extracted from the CD71
      positive fraction. In two instances, we observed false-positive results for RhD
      in PCR of DNA obtained from maternal plasma. CONCLUSION: Based on our results,
      flow-cytometric analysis might be proposed as a clinical tool for the non
      invasive prenatal determination of the fetal RhD status independently of fetal
      gender.

PMID- 16912488
TI  - Successful in utero treatment of chronic and massive fetomaternal hemorrhage with
      fetal hydrops.
AB  - BACKGROUND: Massive fetomaternal hemorrhage is an uncommon cause of chronic fetal
      anemia. Without treatment, hydrops fetalis can occur and progress toward death.
      In some cases, an early diagnosis can improve the management. CASE: A patient was
      found to have a fetus with non-immune hydrops related to massive and early
      fetomaternal hemorrhage successfully treated with serial fetal intravascular
      transfusion. After the treatment, ultrasonographic signs of hydrops disappeared
      and the pregnancy resulted in a good fetal outcome. There was no need for
      neonatal transfusion. Neurological examination at 1 month post-natal was normal.
      CONCLUSION: When massive fetomaternal hemorrhage is diagnosed early in the
      pregnancy, serial fetal intravascular transfusion may be an alternative to
      immediate delivery.

PMID- 16912489
TI  - The Almodin-Moron trocar for uterine entry during fetal surgery.
AB  - OBJECTIVE: Compare the use of a newly designed and reusable metal trocar for
      initial uterine entry with the disposable Tulipan-Bruner trocar in creation of a
      hysterotomy for fetal surgery. METHODS: Six consecutive patients undergoing
      hysterotomy for intrauterine repair of myelomeningocele were randomized to
      uterine entry either with the Tulipan-Bruner trocar or with the Almodin-Moron
      trocar. Blood loss was estimated by the primary surgeon. RESULTS: There was no
      statistically significant difference in the uterine entry times between the
      trocars. Blood loss was estimated to be approximately the same. The Almodin-Moron
      trocar was judged to provide easy handling with good safety. CONCLUSIONS: The
      Almodin-Moron trocar provides a uterine entry during creation of a hysterotomy
      that is as quick and causes as little trauma as the Tulipan-Bruner trocar.

PMID- 16912490
TI  - Venous-arterial Doppler ratios in the prediction of acidemia at birth in
      pregnancies with placental insufficiency.
AB  - OBJECTIVES: Investigate the prediction of birth acidemia in pregnancies with
      placental insufficiency using two newly created venous-arterial Doppler ratios:
      pulsatility index (PI) of the ductus venosus (DV) over PI of the middle cerebral
      artery (MCA) and PI of the DV over PI of the umbilical artery and establish cut
      off values for this prediction. METHODS: This was a prospective cross-sectional
      study involving 47 patients with placental insufficiency managed in two Brazilian
      hospitals. All pregnancies were singleton, over 26 weeks of age and without
      structural or chromosome anomalies. A ROC curve was calculated for the venous
      arterial ratios (independent variable) and acidemia (dependent variable).
      RESULTS: The DV/AU PI ratio was not a good predictor of acidemia at birth. The
      DV/MCA PI ratio was related to fetal acidemia (area under the ROC curve 0.785, p
      = 0.004). The cut-off value was 0.582, sensibility 66.7%, specificity 77.1% and
      accuracy 74.5%. CONCLUSIONS: The DV/MCA PI ratio is adequate for the diagnosis of
      acidemia at birth in pregnancies with placental insufficiency. The cut-off value
      was 0.582.

PMID- 16912491
TI  - Spontaneous rupture of fetal sacrococcygeal teratoma.
AB  - With recent advances in technology, fetal sacrococcygeal teratoma is being
      diagnosed increasingly during the early prenatal period by ultrasound
      examination. In addition, early detection of tumor related complications such as
      polyhydramnios, congestive heart failure, hydrops, hemorrhage, urinary tract or
      bowel obstruction can be followed closely in utero. Active prenatal management
      can improve fetal perinatal outcome by allowing planned delivery for neonatal
      surgery [Chisholm, C.A. et al.: Am J Perinatol 1999;16:47-50] or in some cases,
      fetal intervention. Additionally, families can be counseled appropriately
      regarding the range of outcomes. We report a case of fetal sacrococcygeal
      teratoma Type I diagnosed at 20 weeks with a prominent vessel supplying the tumor
      mass. At 23 weeks, there was a sudden appearance of an additional lobular mass,
      consistent with intrauterine spontaneous ruptured of a sacrococcygeal teratoma
      mass.

PMID- 16912492
TI  - Early and rapid prenatal diagnosis of monosomy 2q36.1 in trophoblast cells.
AB  - OBJECTIVES: CVS is the earliest procedure for cytogenetic analysis but the
      quality of metaphases obtained does not allow the characterization of subtle
      chromosomal anomalies. We report the application interphase fluorescence in situ
      hybridization for the rapid prenatal diagnosis of a subtle structural chromosome
      anomaly in trophoblast cells. METHODS AND RESULTS: The foetus was karyotyped
      because of a paternal complex chromosomal anomaly
      46,XY,inv(2)(q14.3q35),ins(10;2)(q25;q36.1q36.1). Fluorescence in situ
      hybridization analyses were performed on interphase nuclei and metaphase
      chromosomes from uncultured chorionic villi using bacterial artificial
      chromosomes specific for the 2q chromosomal region. Direct conventional
      cytogenetics showed an apparently normal male karyotype, whereas fluorescence in
      situ hybridization analysis showed a deletion of the chromosomal region 2q36.1
      and a paracentric inversion of the chromosome 2q leading to a partial monosomy
      2q36.1. CONCLUSION: This strategy allowed us to offer an early and rapid
      chromosomal analysis for this couple leading to a better management of the
      pregnancy. This report demonstrates that interphase fluorescence in situ
      hybridization can be used in direct CVS for a rapid and early prenatal diagnosis
      of complex chromosomal rearrangements.

PMID- 16912493
TI  - Interest of foetal nasal bone measurement at first trimester trisomy 21
      screening.
AB  - OBJECTIVES: The purpose of this study is to assess the feasibility of foetal
      nasal bone (NB) measurement during the first trimester of pregnancy, and to
      examine the contribution of this measurement to the prenatal screening for Down
      syndrome following the definition of NB threshold using ROC curves in an
      unselected population. METHODS: This prospective study was carried out at our
      centre SIHCUS-CMCO (reference centre) from January 2002 to December 2004 on a
      total of 2,044 pregnant outpatients at gestational weeks 11-14. Only 1260
      singleton foetuses were used for statistical analysis. In the 784 other patients,
      we were unable to obtain a correct image allowing a reproducible measurement. NB
      was measured during the same session as nuchal translucency (NT) measurement. Ten
      trained sonographers took part in the study. Correlation index was evaluated to
      shed light on a link between interest variables and NB. Screening values of NB
      measurement in T 21 were also calculated with NB measurement according to crown
      rump length, and expressed as the best threshold of multiple of the median
      determined by ROC curve. Screening values of genetic ultrasound were then
      evaluated by adding NB measurement to maternal age and NT measurement. RESULTS:
      Two thousand and forty-four patients were included. We indexed 30 cases of T 21,
      14 cases of Trisomy 18, 10 cases of Trisomy 13 and 25 cases of other karyotype
      abnormalities. Feasibility of measurement was 62% of all cases. We observed a
      significant relation between NB and NT (p = 0.001 ), as well as between NB and
      crown-rump-length (p < 0.0001 ). However, size of NB was not correlated to
      maternal ethnic group (p = 0.314). At 0.6 multiple of the median thresholds,
      screening values of NB measurement in T 21 were: sensibility 32%, false positive
      rate 10%, positive predictive value 13.6%, and negative predictive value 96.9%.
      The likelihood ratio for T 21 in case of NB < or = 0.6 multiple of the median was
      4.4 (2.0-9.4). Screening values for maternal age and NT measurement were:
      sensitivity 88%, false positive rate 23%,positive predictive value 9.7%, and
      negative predictive value 99.6%. Inclusion of NB measurement increased
      sensitivity to 100%, positive predictive value to 13.6%, and negative predictive
      value to 100%, and decreased false positive rate to 5%. CONCLUSION: NB
      measurement seemed to be a great sonographic marker for T 21. However, its low
      feasibility made it inadequate for routine settings in first trimester T 21
      screening in an unselected population. Statistical independence with NT thickness
      needed to be further evaluated.

PMID- 16912494
TI  - Maternal mirror syndrome after in utero aortic valve dilation. A case report.
AB  - Fetal hydrops of various etiologies can be associated with maternal mirror
      syndrome. The exact pathophysiology of this rare disorder remains unclear, yet it
      can result in significant maternal and fetal morbidity. The recent advances in
      prenatal diagnosis and therapeutic interventions have focused on altering the
      course of pathologies associated with an expected poor prognosis. Severe fetal
      aortic valve stenosis with its potential for hypoplastic left heart fit this
      category. We report a case of maternal mirror syndrome in a parturient following
      intrauterine therapy for severe fetal aortic stenosis and hydrops. Despite a
      technically successful intervention, the mother required emergency cesarean
      section. We review the few reports of mirror syndrome as well as the current
      approaches to fetal aortic stenosis. This case reinforces the need for in depth
      risk analysis prior to fetal interventions. It also emphasizes the advantage of
      earlier detection and therapy with fetal aortic stenosis since fetal hydrops
      carries a somber prognosis.

PMID- 16912495
TI  - Fetal sheep development on ultrasound and magnetic resonance imaging: a standard
      for the in utero assessment of models of congenital abnormalities.
AB  - OBJECTIVE: To establish normative data for the size, conspicuity, and imaging
      characteristics of normal developing fetal sheep organs on ultrasound (US) and
      magnetic resonance (MR) imaging. METHODS: US and MR images of ten normal pregnant
      sheep, at 40, 65, 90, 115, and 140 gestational days (term = 145 days), were
      scored for organ conspicuity and imaging characteristics. Imaging biometry was
      correlated with specimens. Gestational age-based growth parameters were modeled
      using regression. RESULTS: Imaging biometry showed excellent correlation with
      specimens. Kidney, bladder, stomach, lung, liver, and spine were seen well from
      65 days to term by US. More organs were consistently visible from 90 days to term
      by MR than by US. Most organ imaging characteristics tended not to change
      throughout gestation. CONCLUSION: Normal fetal sheep biometry, organ conspicuity,
      and imaging characteristics are established for US and MR and have potential use
      for the in utero assessment of sheep models of congenital abnormalities.

PMID- 16912496
TI  - Fetal myocardial thickening measured by ultrasonic-based technique called 'phased
      tracking method'.
AB  - OBJECTIVE: To evaluate fetal myocardial movement by using newly developed
      ultrasonic technique. METHODS: We analyzed 50 normal fetuses between 25 and 41
      weeks' gestation for changes in thickness of fetal myocardium using the phased
      tracking method, a technique with high vertical distance resolution and the
      potential to evaluate fine ventricular wall movements. We analyzed differences in
      the rate of change in ventricular wall thickness and in changes in the inner and
      outer wall layers with advancing gestation. We also analyzed myocardial
      thickening period and evaluated the ratio of increasing thickness period to
      stroke interval. RESULTS: Mean thickness changing rate was significantly higher
      in the right (1.18 +/- 0.34 m/s/m) than in the left ventricular wall (0.86 +/
      0.31 m/s/m) (p < 0.001). Mean ratio of increasing thickness period to stroke
      interval was significantly higher in the right (0.57 +/- 0.064) than in the left
      ventricle (0.46 +/- 0.075) (p < 0.001), indicating that myocardial contraction in
      the fetal right ventricle predominates. The thickness-changing rate of the
      bilateral ventricular walls was positively and linearly correlated with
      gestational age. The myocardial-wall thickness-changing rate was higher in the
      outer layer than in the inner layer in late gestation. CONCLUSIONS: We conclude
      that measurement of the thickness-changing rate of fetal ventricular walls using
      the phased-tracking method might be useful for evaluation of fetal cardiac
      function.

PMID- 16912497
TI  - First trimester ultrasound diagnosis of lethal multiple pterygium syndrome.
AB  - OBJECTIVE: Diagnosis of lethal multiple pterygium syndrome in the first trimester
      of pregnancy. METHODS: A 38-year-old woman attended our ultrasound (US) clinic at
      11.2 weeks gestation. She has had two previous stillbirths affected by lethal
      multiple pterygium syndrome. Transabdominal and transvaginal US were performed
      and identified a recurrence. Autopsy findings are compared to the fetal US
      findings. RESULTS: Fetal US showed a markedly increased nuchal translucency,
      fixed flexion deformities of the elbows and knees bilaterally, cutaneous webs
      across both elbow joints and absent fetal movements. The patient decided to
      terminate the pregnancy and a D&C was performed. Pathology of intact fetal parts
      showed flexion deformity of the right elbow with a cutaneous web, and ulnar
      deviation of the right wrist. CONCLUSION: Increased nuchal translucency, absent
      limb movements, multiple joint contractures and cutaneous webs on US allowed the
      diagnosis of lethal multiple pterygium syndromes in the first trimester of
      pregnancy.

PMID- 16912498
TI  - Laser ablation of foetal microcystic lung lesion: successful outcome and
      rationale for its use.
AB  - OBJECTIVE: A foetus with an echodense, microcystic lung lesion complicated by non
      immune hydrops has a high mortality rate. Because of the limited treatment
      options available, laser ablation was offered in an attempt to reduce the size of
      the lesion and reduce hydrops fetalis. METHODS AND RESULTS: A 25-year-old
      nulliparous woman presented at 21 weeks gestation. Ultrasound revealed a male
      foetus with a large microcystic right sided lung lesion that completely occupied
      the right hemithorax causing marked mediastinal deviation. The foetus was
      hydropic with polyhydramnios. Percutaneous laser ablation of the large
      microcystic lung lesion was performed under direct ultrasound control. At a power
      setting of 45 W, and using a 400 microm Nd:YAG laser fibre, the core of the
      lesion was photocoagulated in pulses lasting 5 s at 5 s intervals. The total
      target dose was 1683 J. This led to a marked but temporary reduction in amniotic
      fluid volume. The patient was commenced on sulindac and amniodrainage was
      performed at 27 weeks as reaccumulation of the polyhydramnios occurred. Pre
      eclampsia complicated the pregnancy at 38 weeks gestation and an emergency
      caesarean section was performed. The baby underwent a thoracotomy and lobectomy
      at 48 h of age, made a good recovery, and is currently well 8 weeks post
      delivery. CONCLUSIONS: In cases of cystic lung lesion complicated by hydrops,
      laser ablation should be considered as a treatment option.

PMID- 16912499
TI  - Successful term pregnancy after B-Lynch compression suture in a previous
      pregnancy on account of massive primary postpartum hemorrhage.
AB  - A case is presented of a successful term pregnancy in a 28-year-old secundipara
      after previous Misgav-Ladach cesarean section and B-Lynch compression suture on
      account of massive postpartal hemorrhage caused by uterine atony. On account of
      dystocia and relative cephalopelvic disproportion, secondary repeated cesarean
      section was performed; she gave birth to a live child 3,900 g/52 cm, Apgar score
      9/10, with a regular neonatal course. During the repeated cesarean section, thin
      laces of connective tissue were found along the sutures placed on the uterus
      during the previous B-Lynch operation. Pelvic and intrauterine adhesions were not
      found.

PMID- 16912500
TI  - Thoraco-omphalopagus conjoined twins detected at as early as 9 weeks of
      gestation: transvaginal two-dimensional ultrasound, color Doppler and
      fetoplacental Doppler velocity waveform findings.
AB  - Here we report a case of conjoined twins that were diagnosed antenatally by
      routine two-dimensional transvaginal ultrasound examination at as early as the
      9th week of gestational age. The fetuses were of the thoraco-omphalopagus type
      and were sharing the liver, as confirmed by color Doppler. There was a reversed
      flow in the single ductus venosus of the twins. Umbilical arterial and venous
      blood flow waveform did not show any abnormality for this gestational age. This
      case demonstrated the possibility of making an accurate diagnosis of conjoined
      twins in the first trimester by transvaginal two-dimensional ultrasound and color
      Doppler examination. Although conjoined twins were described at first trimester
      before, fetoplacental Doppler waveform findings at this gestational age have been
      described very rarely. This case demonstrated the possibility of making an
      accurate diagnosis of conjoined twins and delineating the extent of organ sharing
      in the first trimester, and early diagnosis can help the parents with the option
      for pregnancy termination. The importance of expert early vaginal sonography and
      color Doppler findings is emphasized.

PMID- 16912501
TI  - Spontaneous tool use by wild capuchin monkeys (Cebus libidinosus) in the Cerrado.
AB  - Among primates, only chimpanzees and orang-utans are credited with customary tool
      use in nature. Among monkeys, capuchins stand out with respect to the number of
      accounts of tool use. However, the majority of capuchin tool use observations
      reported in nature is anecdotal or idiosyncratic. In this report, we documented
      the stone pounding of dry fruits (Hymenea courbaril and Acrocomia aculeata) in
      two wild free-ranging groups of Cebus libidinosus in the Brasilia National Park,
      a preserved area representative of the Cerradobiome of Central Brazil. In 2004,
      we noted 2 episodes at which 4 monkeys used stones to crack open nuts. In 2005,
      we recorded 5 pounding episodes involving 2 different monkeys. Observations of
      tool use over the course of 2 consecutive years by some individuals, as well as
      other indirect evidence, indicate that this behaviour could be habitual in the
      studied groups. We propose that the probability of the emergence of the use of
      pounding stones as tools may be dependent on the ecological variables that
      influence the degree of terrestriality and extractive foraging and the complex
      interaction of these factors.

PMID- 16912502
TI  - Sexual swellings of female gibbons.
AB  - Female gibbons were observed for labial swellings from March 2002 to August 2003.
      Data were collected on length of time each female was swollen, changes in
      swelling period as females matured, and cycle length (number of days between
      onsets of consecutive swellings). Data were also collected on the behaviour of
      the males when the females were swollen. There was a significant relationship
      between age of the female gibbon and number of days she had labial swelling.
      There was no significant relationship between the age of the gibbon and the cycle
      length, nor between species (Hylobates agilis albibarbis and Hylobates muelleri)
      and number of days swollen. Copulation was more common when females were swollen.
      Swelling in female gibbons may be related to copulatory behaviour and serve to
      provide the male with some certainty of paternity through fertilisation
      insurance.

PMID- 16912503
TI  - High frequency of postcoital penis cleaning in Budongo chimpanzees.
AB  - Cultural or tool use behaviours are typically conducted in social or food
      procurement contexts where the individual interacts with conspecifics,
      heterospecifics or environmental features. We report on postcoital penis cleaning
      in chimpanzees, an activity that does not fit this pattern. In penis cleaning,
      leaves are employed as 'napkins' to wipe clean the penis after sex.
      Alternatively, the same cleaning motion can be done without leaves, simply using
      the fingers. Not all chimpanzee communities studied across Africa clean their
      penes and, where documented, the behaviour is rare. By contrast, we identify
      postcoital penis cleaning in Budongo Forest, Uganda, as customary and corroborate
      penis cleaning as another cultural trait in chimpanzees, one that is specific to
      only a subset of the eastern subspecies of chimpanzee (Pan troglodytes
      schweinfurthii).

PMID- 16912504
TI  - Sanje mangabey Cercocebus sanjei kills an African crowned eagle Stephanoaetus
      coronatus.
AB  - We present the first ever reported observations of a hunting African crowned
      eagle Stephanoaetus coronatus being killed by a primate, in the Udzungwa
      Mountains of south-central Tanzania. An adult female eagle launched an attack on
      a young Sanje mangabey Cercocebus sanjei who was feeding in a tree, but was
      intercepted and bitten by an adult mangabey who was feeding nearby. The adult
      mangabey and the eagle then fell together 25 m to the forest floor below. The
      eagle subsequently died from her injuries, while the mangabey escaped and is
      thought to have survived. This rare event is briefly discussed in the context of
      previous accounts of primate-crowned eagle interactions.

PMID- 16912505
TI  - Male dominance rank, mating and reproductive success in captive bonobos (Pan
      paniscus).
AB  - In the recent past, application of DNA genotyping techniques has enabled
      researchers to more accurately test relationships between dominance rank (DR),
      mating success (MS) and reproductive success (RS). Paternity studies often reveal
      that reproductive outcome does not always correlate with male DR and/or MS and
      thus open room for discussion and interpretation of alternative reproductive
      tactics of both sexes. In this study, we analysed male DR, MS and RS in a group
      of bonobos at Twycross Zoo (UK). Genetic relationships were determined using 8
      tetrameric microsatellite loci. Despite clear and asymmetric dominance
      relationships, analysed using normalised David's scores based on a dyadic index
      of dominance among the group's 3 mature males, we found that the most dominant
      male did not sire the most offspring. In fact, both infants conceived during the
      observation period were found to be sired by the lower-ranking males. Although
      the alpha male had almost exclusive mating access to one of the females during
      the time she was showing a maximal anogenital swelling, her infant was sired by
      the lowest-ranking male who mostly mated with her when outside the maximal
      swelling period. This result suggests that either sperm competition operates
      and/or ovulation is decoupled from the phase of maximal anogenital swelling which
      could allow greater female choice.

PMID- 16912506
TI  - Population dynamics of a group of lion-tailed macaques (Macaca silenus)
      inhabiting a rainforest fragment in the Western Ghats, India.
AB  - We observed the overall population dynamics and number of births and deaths in
      identified individuals between January 2002 and October 2005, in a large group of
      lion-tailed macaques in the Anaimalai Hills of the Western Ghats in the south
      Indian state of Tamilnadu. The group inhabited an isolated rainforest fragment
      located inside a private tea/coffee garden. The group size increased from 56 in
      January 2002 to 84 in October 2005. All females reproduced, and the interbirth
      interval was 23.18 months. Of the 37 infants born between 2002 and 2005, only 1
      died providing an infant survivorship rate of about 97.3%. Although births
      occurred in all months, most of the infants were born between February and March,
      and this pattern of births was consistent over the years, indicating a major
      birth peak in this species. The population growth rate in this unusually large
      group was found to be higher than even in those groups of lion-tailed macaques
      that inhabit large and relatively undisturbed rainforest complexes. This high
      growth rate could be attributed to the availability of abundant cultivated fruit
      plants including commercial crops such as coffee seeds. The observations provide
      a perspective for the management of other groups of this endangered species
      inhabiting rainforest fragments.

PMID- 16912507
TI  - Single-nucleotide polymorphisms in the epsilon-globin gene for differentiating
      primate infraorders.
AB  - Molecular methods are being used to enforce wildlife conservation laws by
      identifying the species or the geographic origin of an unknown sample. However,
      the promising use of single-nucleotide polymorphisms (SNPs) in this field is
      still widely unexplored. In the present work, we have developed a reliable and
      easy method based on single-base extension technology for the scoring of 3 SNPs
      in the epsilon-globin gene that successfully identifies the primate infraorder a
      sample belongs to. Since primates are of high conservation concern and different
      infraorders are distributed in specific parts of the world, this method will
      serve for an initial potentially automated screening of the taxonomy and
      geographic origin of an unknown primate sample arriving at customs.

PMID- 16912508
TI  - Co-localization of susceptibility loci for psoriasis (PSORS4) and atopic
      dermatitis (ATOD2) on human chromosome 1q21.
AB  - Psoriasis (PS) is a chronic inflammatory skin disorder characterized by
      keratinocyte hyperproliferation and altered differentiation. Atopic dermatitis
      (ATOD) is a chronic inflammatory, pruritic and eczematous disease frequently
      associated with respiratory atopy. These diseases are associated with distinct
      immunologic abnormalities and represent typical examples of complex diseases
      triggered by both genetic and environmental factors, as demonstrated by
      independent twin studies. Genome wide linkage studies have mapped susceptibility
      loci on several chromosomes (PSORS1-9; ATOD1-5). Four of them overlap on
      chromosomes 1q21, 3q21, 17q25 and 20p although ATOD is quite distinct from PS and
      these two diseases rarely occur together in the same patient. An association fine
      mapping study has been performed to refine PSORS4 and ATOD2 susceptibility loci
      on chromosome 1q21 analyzing two independently collected cohorts of 128 PS and
      120 ATOD trios. Genotype and haplotype analysis of PSORS4 and ATOD2 led us to
      detect significant p value for haplotypes defined by MIDDLE and ENDAL16 markers
      in both PS (p = 0.0000036) and ATOD (p = 0.0276), suggesting a strict co
      localization within an interval of 42 kb. This genomic interval contains a single
      gene, LOR, encoding for loricrin. Polymorphic markers mapping in regulatory and
      coding regions did not show evidence of association in neither of the two
      diseases. However, expression profiles of LOR in skin biopsies have shown reduced
      levels in PS and increased levels in ATOD, suggesting the existence of a specific
      misregulation in LOR mRNA production.

PMID- 16912509
TI  - Differences in serum GH cut-off values for pharmacological tests of GH secretion
      depend on the serum GH method. Clinical validation from the growth velocity score
      during the first year of treatment.
AB  - BACKGROUND: The serum GH cut-off value for pharmacological tests of GH secretion
      (PhT GH) depends on the type of test and also on the method used for determining
      serum GH. Cut-off serum GH values as different as 5-10 ng/ml, have been reported,
      and have been validated biochemically. We have used the growth velocity (GV)
      standard deviation score (SDS) during the first year of treatment with rhGH to
      validate these cut-offs on a biological basis. METHODS: Fifty pre-pubertal
      patients with short stature (height < or =-2 SDS and GV < or =-1.2 SDS) were
      studied. GH deficiency (GHD) was diagnosed in 39 patients, on the basis of
      clinical and auxological parameters and on the serum concentration of IGF-1, and
      non-GHD in the other 11 patients. Two PhT GH (arginine and clonidine) were
      carried out in the 50 patients. Serum GH was determined by two different methods:
      one detecting most of serum GH isoforms, named Total GH (HGH Bio-Tech, MAIA
      Clone), and another one, only detecting the 22 kDa GH, named 22K GH (GH-22K IFMA,
      Wallac). RESULTS: Basal data: all patients with GHD and with non-GHD had maximal
      serum GH response (MaxR) values below and above the cut-off, respectively, for
      the serum Total GH and 22K GH. The mean 22K GH/Total GH ratio was similar to
      previous publications. Post-rhGH treatment data: the two groups improved their
      height SDS during the first year of treatment, particularly patients with GHD. A
      receiver-operator curve was used to define the best threshold for post-treatment
      GV-SDS that separates GHD from non-GHD patients. This value was 1.91 GV-SDS. A
      negative correlation between first year treatment GV-SDS and pre-treatment serum
      GH MaxR was found for the two assays (p < 0.001). Then, the best cut-off GV-SDS,
      previously calculated with the receiver-operator curve (1.91 SDS) was used to
      interpolate the corresponding serum GH values, as determined by the two methods.
      For Total GH, the value was 10.8 ng/ml, and for 22K GH, it was 5.4 ng/ml.
      CONCLUSION: The cut-off values calculated by biological means to separate GHD
      from non-GHD were remarkably similar to those calculated biochemically (10.0 and
      4.8 ng/ml, respectively) for Total and 22K GH. This is a biological validation
      for using different cut-off values, appropriate for each assay, to diagnose GHD.

PMID- 16912510
TI  - Correlation between serum osteoprotegerin and biomarkers of bone metabolism
      during anti-thyroid treatment in patients with Graves' disease.
AB  - Bone turnover is increased in favor of resorption in hyperthyroid patients. We
      aimed to examine whether osteoprotegerin (OPG), which has an inhibitory effect on
      osteoclasts, is correlated with any biomarkers for bone turnover in Graves'
      disease. Twenty-one patients with Graves' disease were examined in this study,
      before and after treatment. Briefly, OPG, calcium, phosphorus, PTH, free T3, free
      T4, TSH, TSH receptor antibody and TSH-stimulating antibody were measured.
      Elevated serum OPG levels were decreased in accordance with anti-thyroid
      treatment. This change of OPG level was associated with thyroid hormone free T4
      (r = 0.175, p = 0.038) but not with free T3 (r = 0.164, p = 0.052) and TSH (r =
      0.046, p = 0.59). Additionally, there was a negative correlation between OPG and
      PTH (r = -0.37, p = 0.0001). In stepwise regression analysis, the change in serum
      OPG levels during anti-thyroid treatment was significantly and independently
      associated with PTH (F ratio = 24.4, p < 0.0001). Our findings suggest that OPG
      may prevent excessive bone loss in the hyperthyroid state in accordance with the
      change of biomarkers for bone turnover.

PMID- 16912511
TI  - Effects of early high-dose levothyroxine treatment on auditory brain event
      related potentials at school entry in children with congenital hypothyroidism.
AB  - AIMS: We tested whether brain event-related potentials (ERPs) are normal in
      children with congenital hypothyroidism (CH) after early high-dose levothyroxine
      treatment. METHODS: Auditory ERPs were recorded in 33 normal controls and in 15
      children with CH at 5 years 9/12. Based on bone maturation at diagnosis, the CH
      group was divided into severe (n = 8) and moderate (n = 7) subgroups. CH patients
      were treated at a median age of 14 days with a mean initial dose of levothyroxine
      of 11.6 microg/kgxday. Two ERP components (N100 and N200) were measured and
      clinical follow-up variables collected. RESULTS: The functional anatomical and
      cognitive organisation of the auditory system, as revealed by the analyses of ERP
      measures, did not differ between CH and controls, or between severe and moderate
      CH subjects. However, N200 latency was globally longer in the CH than in the
      control group (p = 0.01) and was positively correlated with the over-treatment
      index (r = 0.61; p < 0.05) and verbal IQ. N200 amplitude was negatively
      correlated with initial dose (r = -0.74; p < 0.005). CONCLUSION: These data
      suggest that sensitive tools such as ERPs can reveal differences between CH and
      controls and relate these differences to the adequacy of treatment of CH.

PMID- 16912512
TI  - Roles of paraoxonase and oxidative stress in adolescents with uraemic, essential
      or obesity-induced hypertension.
AB  - BACKGROUND/AIMS: Paraoxonase 1 (PON1) is associated with high-density
      lipoproteins in the plasma, and is capable of hydrolysing oxidized lipids and
      preventing the oxidation of low-density lipoproteins. Oxidative stress and the
      PON1 (activity and Q192R polymorphism) were analysed in adolescent patients with
      essential (n = 49) or obesity-induced hypertension (n = 79), uraemic patients (n
      = 20), and also in obese normotensive patients (n = 60) and age-matched controls
      (n = 57). METHODS: The PON1 activity was measured via paraoxon hydrolysis. The
      PON1 genotype was determined by real-time PCR. The levels of oxidized and reduced
      glutathione, the end-products of nitric oxide, cysteine, homocysteine and lipid
      peroxidation in the plasma were measured and related to the PON1 status. RESULTS:
      There were no significant differences between the patient groups and the control
      group in the genotype distributions and the allele frequencies of the Q192R
      polymorphism. The PON activity was significantly lower (p < 0.001) in the uraemic
      hypertensive group than in the controls. The MDA concentration was significantly
      higher in the uraemic hypertensive (p < 0.001) and obese hypertensive (p < 0.05)
      patients. The plasma NOx concentrations were significantly lower (p < 0.001) and
      the ratio MDA/NOx were significantly higher in all four patient groups. The GSH
      levels were significantly lower in the patients with hypertension (p < 0.001) and
      obesity-induced hypertension (p < 0.05) than in the controls, while the GSSG
      level (p < 0.01) and the ratio GSSG/GSH (p < 0.05) was significantly higher in
      the uraemic hypertensive group. The plasma homocysteine level was significantly
      higher (p < 0.001) in the uraemic hypertensive patients as compared with the
      controls. CONCLUSIONS: We found no significant correlation between the
      biochemical parameters and neither genotypes nor enzyme activities. The PON1
      status and the levels of certain biochemical parameters are independently
      associated with the hypertension in hypertensive and obese hypertensive patients,
      and the elevated levels of lipid peroxides and plasma homocysteine may contribute
      to the increased risk of cardiovascular complications in patients on
      haemodialysis.

PMID- 16912514
TI  - Angiogenesis in uveal melanoma.

PMID- 16912513
TI  - Familial risks for epilepsy among siblings based on hospitalizations in Sweden.
AB  - PURPOSE: Epilepsy is a common disabling condition, with high heritability
      according to twin studies. Characterization of familial risks for common subtypes
      of epilepsy will advance the search for the heritable causes of these conditions
      and their underlying mechanisms. We aim at defining familial risks for siblings
      to be hospitalized because of epilepsy. METHODS: A nationwide ad hoc epilepsy
      database was constructed by linking the Multigeneration Register on 0- to 69-year
      old siblings to the Hospital Discharge Register for data on epilepsies covering
      the years 1987-2001. Standardized risk ratios (SIRs) were calculated for affected
      sibling pairs by comparing them to those whose siblings had no epilepsy. RESULTS:
      Among a total of 26,799 hospitalized cases, 598 affected siblings were identified
      with a familial SIR of 2.35; the SIR was highest at ages 0-4 years (6.82).
      Infantile spasms showed the highest risk for any subtype (10.45), when a co
      sibling was diagnosed with any epilepsy. When both siblings were diagnosed with a
      concordant (same) subtype of epilepsy, the SIRs were high, i.e. 8.43 for
      generalized idiopathic epilepsy, 2.56 for partial epilepsy, 24.72 for status
      epilepticus and 24.39 for other epilepsies. Generalized idiopathic epilepsy was
      also associated with grand mal (4.06) and other epilepsies (7.61). The numbers of
      cases were small but concordant diagnoses always showing higher SIRs compared
      with discordant diagnoses. CONCLUSIONS: Within the limits of the present sample
      size, our results suggest high familial aggregation for certain subtypes of
      epilepsy for which distinct genetic mechanisms may underlie.

PMID- 16912515
TI  - Methadone doses upon multiple readmissions to inpatient detoxification: Clinical
      evidence for very moderate opioid tolerance.
AB  - Escalation of drug use by addicts has traditionally been interpreted as tolerance
      to the drug's effects. On the basis of animal behavioral data, several groups
      have recently proposed alternative explanations, i.e., that such an escalation of
      drug dose might not be based on tolerance but rather be indicative of (i)
      sensitization to the reinforcing effect or the incentive salience of the drug of
      abuse or (ii) shifts in baseline mood, i.e., allostasis. In the present study,
      the emergence of opioid tolerance or sensitization during the progression of
      opioid dependence was assessed by comparing the methadone doses that were
      initially required to alleviate the opioid withdrawal symptoms of intravenous
      opioid users who presented for detoxification upon 3-7 consecutive admissions
      over the course of up to 84 months. Upon the second admission, the 48 surveyed
      male patients needed 115 +/- 6% (p = 0.012) and the 32 female patients needed 121
      +/- 12% (p = 0.01) of the methadone dose required upon the first admission. Upon
      the third admission, the respective values were 121 +/- 8% (males; p = 0.013) and
      111 +/- 12% (females; n.s.), and upon the fourth admission, 125 +/- 14% (males; p
      = 0.026) and 131 +/- 14 (females; p = 0.01). Inter-admission intervals averaged
      14 +/- 1 months (n = 135) for males and 13 +/- 1 months (n = 91) for females and
      were not significantly different across consecutive admissions, suggesting that
      tolerance did not develop faster upon repetition of abuse-withdrawal cycles. In
      conclusion, the intravenous opioid users surveyed in the present study developed
      only very moderate tolerance during the repeated abuse-detoxification cycles that
      were typical for their disease progression. The present data do not support the
      notion that sensitization to the opioids' reinforcing effects occurred in this
      naturalistic clinical sample.

PMID- 16912516
TI  - Treatment with cyclohexenonic long-chain fatty alcohol reverses diabetes-induced
      tracheal dysfunction in the rat.
AB  - In this study, we tried to elucidate the effect of cyclohexenonic long-chain
      fatty alcohol (N-hexacosanol) on tracheal dysfunction in diabetic rats. Diabetes
      was induced in 8-week-old male Sprague-Dawley rats by administering an
      intraperitoneal injection of 50 mg/kg streptozotocin. Non-diabetic control rats
      received an injection of citrate-phosphate buffer alone. Four weeks after the
      induction of diabetes, rats were randomly divided into 5 groups: age-matched non
      diabetic control rats (group A); 4-week diabetic rats without N-hexacosanol
      treatment (group B); diabetic rats treated with vehicle (group C), and diabetic
      rats treated with N-hexacosanol at a dose of 2 or 8 mg/kg i.p. every day for the
      following 4 weeks (group D and group E, respectively; n = 6-8 animals in each
      group). Serum glucose and insulin levels were determined, as were the contractile
      responses induced by carbachol and 100 mmol/l KCl. The participation of M(2) and
      M(3) receptors was investigated in the trachea by real-time polymerase chain
      reaction (PCR), hematoxylin and eosin (HE) and immunohistochemical staining.
      Hypertrophy of airway smooth muscle was observed in diabetic rats, and was
      ameliorated by treatment with N-hexacosanol. Treatment with either 2 or 8 mg/kg N
      hexacosanol did not alter diabetic rat status, i.e., body weight, serum glucose
      or serum insulin levels, but it significantly reversed the decrease in tracheal
      wall thickness and diabetes-induced hypercontractility in the rat trachea. In the
      immunohistochemical studies, muscarinic M(2) and M(3) receptors were expressed in
      the airway smooth muscle, the elastic fibers, the fibroblast and the surface of
      epithelium, and these expressions were not altered by either induction of
      diabetes or N-hexacosanol treatment. The expression of M(3) muscarinic receptor
      mRNAs in the trachea tended to be increased by the induction of diabetes and
      normalized when treated with N-hexacosanol. Our data indicate that N-hexacosanol
      could reverse diabetes-induced hypercontractility in the rat trachea.

PMID- 16912517
TI  - Bilateral anterior cingulotomy for refractory obsessive-compulsive disorder: Long
      term follow-up results.
AB  - OBJECTIVE: To investigate the long-term efficacy and adverse cognitive effects of
      stereotactic bilateral anterior cingulotomy as a treatment for refractory
      obsessive-compulsive disorder (OCD) patients. MATERIALS AND METHODS: Seventeen
      patients suffering from refractory OCD underwent stereotactic bilateral anterior
      cingulotomies and were followed for 24 months. The Yale-Brown Obsessive
      Compulsive Scale (Y-BOCS), the Clinical Global Impression and other
      neuropsychological tests were used to assess the efficacy and cognitive changes
      of cingulotomy. The tests were taken before and 12 and 24 months after surgery.
      RESULTS: The mean improvement rate of the Y-BOCS score achieved from the baseline
      was 48%. Eight patients out of 17 met the responder criteria. During the 24-month
      follow-up, there were no significant adverse effects observed after surgery.
      CONCLUSIONS: Bilateral anterior cingulotomy was effective for the treatment of
      refractory OCD, and no other significant adverse cognitive effects on long-term
      follow-up were found.

PMID- 16912518
TI  - [Dihydropyrimidine dehydrogenase activity and its genetic aberrations].
AB  - Dihydropyrimidine dehydrogenase (DPD, EC 1.3.1.2) is the initial and rate
      limiting enzyme in the catabolism of the pyrimidine bases, uracil and thymine,
      and is also known to be the key enzyme catalyzing the metabolic degradation of
      the anti-cancer drug 5-fluorouracil (5-FU). 5-FU has been commonly and widely
      used as a chemotherapeutic agent for the treatment of cancer of the
      gastrointestinal tract, breast, and head and neck. More than 85% of the
      administered 5-FU is catabolized by DPD. The clinical importance of DPD has been
      demonstrated with the identification of severe or lethal toxicity in patients
      administered 5-FU who are deficient in or have low levels of DPD activity in
      their peripheral blood mononuclear cells (PBMC). The importance of the role of
      DPD in 5-FU chemotherapy also has been shown by studies with competitive and
      irreversible DPD inhibitors. Population studies of DPD activity in PBMC were
      reported in healthy volunteers and cancer patients to evaluate the incidence of
      complete or partial DPD deficiency. In these studies, considerable variation was
      observed, and the frequency of low or deficient DPD activity (<30% and <10% of
      the mean activity of the normal population, respectively), was estimated to be 3
      5% and 0.1%,respectively. We also found one healthy volunteer (0.7% of the
      population) with very low PBMC-DPD activity due to heterozygosity for a mutant
      allele of the DPYD gene in a population of 150 healthy Japanese volunteers. To
      date, at least 34 DPYD variants have been reported. However, genotyping of cancer
      patients with reduced or normal DPD activity showed that only 17% of those
      patients had a molecular basis for their deficient phenotype, which emphasized
      the complex nature of the molecular mechanisms controlling polymorphic DPD
      activity in vivo,suggesting that it is difficult to identify DPD deficiency by
      genotyping. Therefore, it is important to develop methods for identifying DPD
      deficiency in cancer patients by phenotyping before 5-FU treatment.

PMID- 16912519
TI  - [Lung cancer with bone metastasis].
AB  - Lung cancer is one of the most common solid tumors to develop metastases to bone.
      The prognosis of patients with metastatic lung cancer to bones is short,usually
      less than 6 months. The treatment requires a multidisciplinary approach that
      addresses radiotherapy, surgery, chemotherapy, and medical therapy with
      analgesics and bisphosphonates. Radiotherapy for metastatic bone tumor is a
      mainstay to relieve pain and control the localized disease. Doses in the range of
      20 Gy in 5 fractions, 30 Gy in 10 fractions are acceptable in most circumstances.
      Prophylactic fixation for long bone fractures is recommended in cases where 30 to
      50% of the cortex has been destroyed, pain is present after radiotherapy, or life
      expectancy is more than 3 months. Systemic chemotherapy has been proved to
      prolong survival of patients with metastatic non-small-cell lung cancer (NSCLC)
      as well as extensive small cell lung cancer (SCLC). Combination chemotherapy of
      platinum and a new drug is recommended in NSCLC patients with good performance
      status (PS). Gefitinib in upfront or second-line treatment is an optional therapy
      in adenocarcinoma patients without a history of smoking. Cisplatin combined with
      etoposide or irinotecan is a standard therapy in SCLC patients with PS 0 or 1.
      Carboplatin and etoposide is a treatment of choice in SCLC patients with PS 2 or
      3. Medical management of cancer pain requires nonsteroidal anti-inflammatory
      drugs and opioids. Cancer pain that necessitates more than 120 mg of oral
      morphine is morphine-resistant pain and requires some adjuvant drugs such as
      corticosteroids, ketamine,anticonvulsants, or local anesthetics. The third
      generation bisphosphonate zoledronate has been demonstrated to improve cancer
      pain and to prevent skeletal morbidity in lung cancer patients with metastatic
      bone disease.